PMID- 22980400
TI  - Self-regulation of unattainable goals in suicide attempters: a two year
      prospective study.
AB  - BACKGROUND: Although suicide is a global public health concern with approximately
      one million people dying by suicide annually, our knowledge of the proximal risk
      mechanisms is limited. In the present study, we investigated the utility of two
      proximal mechanisms (goal disengagement and goal reengagement) in the prediction
      of hospital-treated self-harm repetition in a sample of suicide attempters.
      METHODS: Two hundred and thirty-seven patients hospitalised following a suicide
      attempt completed a range of clinical (depression, anxiety, hopelessness,
      suicidal ideation) and goal regulation measures (goal reengagement and
      disengagement) while in hospital. They were followed up two years later to
      determine whether they had been re-hospitalised with self-harm between baseline
      and the follow-up. RESULTS: Self-harm hospitalisation in the past 10 years,
      suicidal ideation and difficulty reengaging in new goals independently predicted
      self-harm two years later. In addition, among younger people, having difficulty
      re-engaging in new goals further predicted self-harm re-hospitalisation when
      disengagement from existing unattainable goals was also low. Conversely, the
      deleterious impact of low reengagement in older people was elevated when goal
      disengagement was also high. LIMITATIONS: Only hospital-treated self-harm and
      suicide were recorded at follow-up, episodes of less medically serious self-harm
      were not recorded. CONCLUSIONS: Suicidal behaviour is usefully conceptualised in
      terms of goal self-regulation following the experience of unattainable goals.
      Treatment interventions should target the self-regulation of goals among suicide
      attempters and clinicians should recognise that different regulation processes
      need to be addressed at different points across the lifespan.

PMID- 22980401
TI  - Does the installation of blue lights on train platforms prevent suicide? A before
      and-after observational study from Japan.
AB  - BACKGROUND: Railway and metro suicides constitute a major problem in many parts
      of the world. Japan has experienced an increase in the number of suicides by
      persons diving in front of an oncoming train in the last several years. Some
      major railway operators in Japan have begun installing blue light-emitting-diode
      (LED) lamps on railway platforms and at railway crossings as a method of
      deterring suicides, which is less costly than installing platform screen doors.
      However, the effectiveness of the blue lights in this regard has not yet been
      proven. METHODS: This study evaluates the effect of blue lights on the number of
      suicides at 71 train stations by using panel data between 2000 and 2010 from a
      railway company in a metropolitan area of Japan. We use a regression model and
      compare the number of suicides before and after and with and without the
      intervention by the blue light. We used the number of suicides at 11 stations
      with the intervention as the treatment group and at the other 60 stations without
      the intervention as the control group. RESULTS: Our regression analysis shows
      that the introduction of blue lights resulted in a 84% decrease in the number of
      suicides (CI: 14-97%). LIMITATION: The analysis relies on data from a single
      railroad company and it does not examine the underlying suicide-mitigation
      mechanism of blue lights. CONCLUSION: As blue lights are easier and less
      expensive to install than platform screen doors, they can be a cost-effective
      method for suicide prevention.

PMID- 22980402
TI  - Symptom differences between depressed outpatients who are in remission according
      to the Hamilton Depression Rating Scale who do and do not consider themselves to
      be in remission.
AB  - OBJECTIVE: Remission is usually defined as a score below a predetermined cutoff
      on a symptom severity scale. Depressed patients' global perception of their
      remission status only partially overlaps with scale-based definitions of
      remission. Patients' self-perceived remission status is likely to impact on their
      desire for modification in their treatment. The identification of specific
      symptoms that distinguish patients who do and do not consider themselves to be in
      remission could represent the most salient targets of add-on treatment strategies
      desired by patients. In the present report from the Rhode Island Methods to
      Improve Diagnostic Assessment and Services (MIDAS) project, we compared the
      symptom profiles of patients who were in remission on the Hamilton Rating Scale
      for Depression (HAMD) who did and did not consider themselves to be in remission.
      METHODS: We interviewed 274 psychiatric outpatients diagnosed with DSM-IV major
      depressive disorder who were in ongoing treatment. The patients completed the
      Clinically Useful Depression Outcome Scale (CUDOS). RESULTS: Approximately half
      of the patients scoring 7 and below on the HAMD did not consider themselves to be
      in remission. The mean number of symptoms on the CUDOS was significantly higher
      in the self-described non-remitters. Almost all symptoms were less frequent in
      the self-rated remitters, though the absolute frequency of the individual
      symptoms was related to the threshold used to define symptom presence.
      DISCUSSION: Consistent with the findings of other studies we found high rates of
      residual symptoms in patients who were considered to be in remission, and
      patients with residual symptoms typically had more than 1 such symptom. These
      results raise questions about the strategy of add-on treatments targeting
      specific individual symptoms. LIMITATIONS: Remission was defined according to the
      17-item version of the HAMD. We focused on the 17-item HAMD because it is the
      most commonly used measure in antidepressant efficacy trials, and the cutoff used
      to define remission has been generally accepted. We would anticipate that our
      findings would be similar in studies of longer versions of the HAMD as well as
      other depression severity scales such as the Montgomery-Asberg Depression Rating
      Scale. Self-perceived remission status was based on the patients' response to a
      single question. The sample was drawn from a single, large, general adult
      outpatient private practice setting in which the majority of the patients were
      white, female, and in their 30s and 40s. Generalizability to samples with
      different demographic characteristics needs to be demonstrated.

PMID- 22980403
TI  - Aberrant executive attention in unaffected youth at familial risk for mood
      disorders.
AB  - BACKGROUND: Aberrant attentional processes in individuals with mood disorders -
      bipolar disorder (BD) and major depressive disorder (MDD) - have been well
      documented. This study examined whether unaffected youth at familial risk for
      mood disorders would exhibit poor alerting, orienting, and executive attention
      relative to age-matched controls. METHODS: A sample of youth (8-17 years old)
      having one parent with either BD or MDD (Mood-Risk, n=29) and youth having
      healthy parents (HC, n=27) completed the Attention Network Test-Short version
      (ANT-S), which assesses alerting, orienting, and executive attention. RESULTS:
      Relative to HCs, the Mood-Risk group had significantly slower reaction times on
      an index of executive attention, but no differences on indices of alerting or
      orienting. There were no differences between the two at-risk groups (i.e., youth
      with BD parent vs. youth with MDD parent) on any ANT-S measure. LIMITATIONS: The
      current study is limited by its cross-sectional design, small sample size, and
      failure to control for familial environmental factors. CONCLUSIONS: The findings
      extend previous results indicating that altered executive attention may represent
      an endophenotype for mood disorders in at-risk youth.

PMID- 22980404
TI  - Clinical and demographic features associated with the detection of early warning
      signs in bipolar disorder.
AB  - AIM: The detection of early warning signs is a major component of many
      psychological interventions for assisting in the management of bipolar disorder.
      The aim of this study was to assess whether the ability to detect early warning
      signs was associated with clinical and demographic characteristics in a bipolar
      disorder clinic sample. METHOD: Two-hundred-and-one participants with DSM-IV
      bipolar I or II disorder aged over 18 years of age were recruited through a
      specialized bipolar disorder clinic. Participants were administered a structured
      interview by psychiatrists asking participants about any early warning signs, and
      features of the phenomenology, course and treatment of bipolar disorder. RESULTS:
      Participants were significantly more likely to recognise both hypo/manic and
      depressive early warning signs rather than only one type of mood episode. The
      ability to detect signs of both hypo/mania and depression was greater in younger
      participants. The ability to detect signs of depression was associated with more
      prior depressive episodes and a lesser likelihood of prior hospitalisations
      whilst a history of mixed mood was associated with a greater likelihood of
      detecting depressive symptoms. The ability to recognise signs of hypo/mania was
      greater in those reporting a history of visual hallucinations (during depressive
      and/or manic episodes). LIMITATIONS: Cross-sectional design and previous
      experience with psychotherapy was not assessed. CONCLUSION: These findings
      provide useful clinical data pertinent to psychological interventions for bipolar
      disorder. Longitudinal studies are needed to further examine how the ability to
      recognise early warning signs may be associated with longer term outcome.

PMID- 22980405
TI  - Screening for colorectal cancer: what is the impact on the determinants of
      outcome?
AB  - Colorectal cancer screening has been introduced across the UK following several
      large randomised control trials and a Cochrane review that have shown a reduction
      in cancer specific mortality with population based Faecal Occult Blood testing.
      This has been attributed to the detection of more early stage disease. It is well
      known that in addition to stage at presentation there are a variety of other key
      factors that determine a patient's outcome following a diagnosis of colorectal
      cancer. For example there are tumour-related factors, such the presence of venous
      invasion and tumour necrosis, and also host-related factors, both in terms of
      demographic profile and an elevated circulating host inflammatory response that
      have been shown to be predictive of a poorer outcome. The present review
      summarises both the background behind the current screening programme and the
      observed and anticipated impact that colorectal cancer screening will have on the
      key determinants of outcome.

PMID- 22980406
TI  - Bioeffects of ultrasound-stimulated microbubbles on endothelial cells: gene
      expression changes associated with radiation enhancement in vitro.
AB  - Ultrasound can be used to target endothelial cells in cancer therapy where the
      destruction of vasculature leads to tumor cell death. Here, we demonstrate
      ultrasound bioeffects in which the levels of genes in endothelial cells can be
      significantly altered by ultrasound-stimulated microbubble exposure. These were
      compared with established effects of radiation on endothelial cells at a gene
      level. Human-endothelial cells were exposed to ultrasound and microbubbles,
      radiation or combinations of ultrasound, microbubbles and radiation. Gene
      expression analyses revealed an up-regulation of genes known to be involved in
      apoptosis and ceramide-induced apoptotic pathways, including SMPD2, UGT8, COX6B1,
      Caspase 9 and MAP2K1 with ultrasound-stimulated microbubble exposure but not
      SMPD1. This was supported by immunohistochemistry and morphologic changes
      examined with cell microscopy, which showed changes in SMPD1 gene product in
      cells with microbubble exposure. This supports the hypothesis that ultrasound
      stimulated microbubbles can induce significant bioeffect-related changes in gene
      expression and can affect ceramide signaling pathways in endothelial cells,
      leading to apoptosis.

PMID- 22980407
TI  - Acoustic radiation force of a Gaussian beam incident on spherical particles in
      water.
AB  - Based on the finite series method, the Gaussian beam is expanded as spherical
      functions and the beam coefficient of a Gaussian beam is obtained. A new
      expression for the acoustic radiation force function, which is the radiation
      force per unit energy density and unit cross-sectional surface area for a sphere
      in a Gaussian beam, is presented in this paper. Numerical results for the
      radiation force function of a Gaussian beam incident upon the spherical particles
      are presented for rigid spheres, liquid spheres and elastic spheres immersed in
      water to illustrate the theory. The radiation force function vs. ka curve, ka
      being the radius times the wavenumber in the surrounding medium, is discussed for
      different beam widths. The acoustic radiation force function is determined by the
      parameters of the particles, with liquid spheres having smaller values than those
      for rigid and elastic spheres. The beam width also affects the acoustic radiation
      force function. When the radius of the sphere is larger than the beam width, the
      beam width has greater effects on the radiation force. This analysis helps
      analyzing and understanding the effects of the acoustic Gaussian beams on
      spherical objects.

PMID- 22980408
TI  - Abnormal WBC scattergram: a clue to the diagnosis of malaria.
AB  - OBJECTIVE: Malaria is highly prevalent and endemic in tropical countries and
      carries a significant health burden. The detection of malaria by light microscopy
      of Giemsa-stained smears is the gold standard. There are many hematological
      abnormalities associated with malaria like anemia, thrombocytopenia, and
      leucopenia; however, none of these abnormalities are specific. The present study
      was undertaken to assess the utility of WBC scattergram in predicting the
      diagnosis of malaria. METHODS: In this study all cases diagnosed as Plasmodium
      vivax/Plasmodium falciparum infection on peripheral smear examination were
      included. Their complete blood counts and WBC scattergrams obtained from XT2000i
      were critically evaluated. Accordingly, sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value of detection of malaria by
      abnormal WBC scattergram with and without abnormal blood counts were also
      calculated. RESULTS: A total of 2251 ethylendiaminetetraacetic acid samples were
      run on XT2000i hematology autoanalyzer. Out of these 148 cases of malaria were
      diagnosed on peripheral smear (128 P. vivax and 20 P. falciparum). While
      analyzing the WBC scattergrams, 233 cases including 124 (83.8%) malaria cases
      showed different abnormalities. Sensitivity and PPV for the diagnosis of malaria
      by abnormal WBC scattergram were 83.78 and 53.20%, respectively. This had
      increased to 98.60 and 57.25%, respectively, when cytopenias were included.
      DISCUSSION: Sysmex XT-2000i is capable of detecting specific abnormalities in WBC
      scattergram in patients with malaria. Therefore, the presence of an abnormal WBC
      scattergram with thrombocytopenia in a febrile patient helps the pathologist to
      clinch the diagnosis of malaria.

PMID- 22980409
TI  - Early is not necessarily precocious.

PMID- 22980410
TI  - Demographic and relationship predictors of paternity establishment for infants
      born to adolescent mothers.
AB  - STUDY OBJECTIVE: To identify demographic and relationship characteristics
      associated with paternity establishment for children born to adolescent mothers.
      PARTICIPANTS, SETTING, AND DESIGN: This prospective cohort study included 300
      pregnant adolescents 12-19 years old, presenting for prenatal care between March
      2002 and February 2005. Demographic and relationship characteristics were
      compared based on paternity establishment (father's name on the infant's birth
      certificate). MAIN OUTCOME MEASURE: Paternity establishment (father's name on the
      infant's birth certificate). RESULTS: Of the 273 participants with outcome data,
      54% established paternity. Paternity establishment differed by maternal
      race/ethnicity (69% Hispanic vs 36% non-Hispanic Black vs 52% non-Hispanic White,
      P = .01), maternal age (37% for 12-15 years vs 64% for 18-19 years, P = .01),
      maternal country of birth (48% U.S. born vs 76% non-U.S. born, P = .01),
      relationship with father of the infant, and father involvement at the time of
      delivery. CONCLUSION: Paternity establishment rates for children born to teens
      were low overall. To increase rates of paternity establishment, policies and
      programs need to consider the unique characteristics and circumstances of teen
      parents.

PMID- 22980411
TI  - Tampon use in adolescence: differences among European American, African American
      and Latina women in practices, concerns, and barriers.
AB  - PURPOSE: Tampon use is common among European American adolescents, but much less
      so among African American and Latina adolescents. Reasons are largely unclear.
      The general goal of this study was to examine differences among European
      American, African American and English-speaking Latina women and Spanish-speaking
      women in tampon use, sources of information about tampon use, and concerns and
      barriers related to tampon use in their adolescent years. METHOD: The sample
      included 165 low-income women ages 18 to 35 years (M = 24.1) who filled out a
      survey in a family planning clinic. RESULTS: European American women (71%) were
      significantly more likely to use tampons in adolescence compared to a
      considerably smaller proportion of African American (29%), English-speaking
      Latina (22%), and Spanish-speaking Latina women (5%). Mothers were a primary
      source of explanations about tampons for European American women, but not for
      ethnic minority women. African American and Latina English-speaking women were
      more likely to report that their mothers did not approve of tampons compared to
      none of the European American women. Specific concerns about tampons for Latina
      and African American women were that they were unsafe and inappropriate for
      virgins, and also for Latina women, that they could get lost or stuck. Overall,
      Latina women reported more concerns and barriers to tampon use than European
      American women which included a lack of knowledge on how to use them. Findings
      have implications for addressing the health education needs of low-income ethnic
      minority adolescents to reduce misconceptions and relieve concerns about tampons.

PMID- 22980412
TI  - Urogenital symptoms after sexual abuse vs irritant contact in premenarchal girls.
AB  - OBJECTIVES: Sexually abused (SA) girls report urogenital symptoms temporally
      related to inappropriate genital contact. Since girls also experience symptoms
      following genital irritant exposure and mostly all girls are exposed to genital
      irritants, we describe overall symptoms reported by girls that disclosed SA
      compared to those that did not and we compare how girls describe symptoms
      following a specific episode of contact SA vs a genital irritant exposure.
      DESIGN: Cross-sectional study. Parents/girls interviewed; medical records
      reviewed. PARTICIPANTS: Five to 12-year-old premenarchal girls/parents. SETTING:
      An urban and a suburban pediatric practice; a regional treatment center for child
      abuse. OUTCOME MEASURES: Prevalence of histories of urogenital symptoms in SA
      girls compared to girls attending well-child exams (controls); girls' description
      of urogenital symptoms following specific episodes of contact SA compared to
      specific episodes of genital irritant exposure. RESULTS: More parents/girls in SA
      group reported prior urogenital symptoms. Most SA girls said past symptoms were
      caused by inappropriate genital touching; most control girls could not identify
      causes for prior symptoms. Girls' responses following specific irritant
      exposures: 76% SA vs 24% control girls used negative terms to describe how it
      felt, 69% SA vs 6% control girls said it bothered her body and her feelings, and
      33% SA vs 12% control girls described experiencing dysuria afterwards (all ps <
      0.05). CONCLUSIONS: Girls can relate urogenital symptoms to specific genital
      contacts; more SA girls reported unpleasant symptoms with an emotional component.
      A skilled medical history can help differentiate these conditions and diagnose
      sexual abuse with greater certainty.

PMID- 22980413
TI  - Mitotically active cellular ovarian fibroma with Meigs' syndrome and elevated CA
      125: towards fertility preservation.
AB  - BACKGROUND: Meigs syndrome is rare in women under 30 years of age and even more
      if associated with an elevated CA-125. In this case, malignancy was suspected and
      raised concerns about fertility preservation. CASE: A 13-year-old girl presented
      with a 4-month amenorrhea, abdominal enlargement and dyspnea. Ultrasonography
      showed a 14-cm solid mass with ascites, bilateral pleural effusion and,
      analytically, elevated serum CA-125. Unilateral salpingo-oophorectomy was
      performed, with a 19 * 15 * 12 cm mass being disclosed from the right ovary.
      Final pathology diagnosed a mitotically active cellular ovarian fibroma (MACF),
      with no significant nuclear atypia. CONCLUSION: MACF is a recent histopathologic
      entity. Despite the high count of mitotic figures, it is not associated with
      atypia, which contributes to favorable outcome. Although initial suspicions of
      malignancy, a conservative surgical intervention allowed fertility preservation.
      This was clinically appropriate and with no implications on survival and
      prognosis of these patients.

PMID- 22980414
TI  - An atypical growth of a giant fibroadenoma after trauma.
AB  - BACKGROUND: Fibroadenomas are the most common benign breast lesion in female
      adolescents. However, it is important to recognize that a small percentage have
      been shown to progress to giant fibroadenomas. Giant fibroadenomas can
      spontaneously infarct leading to significant morbidity and are also difficult to
      distinguish from the more aggressive phyllodes tumors. CASE: We describe the
      first case, to the best of our knowledge, of a 12-year-old girl who presented
      with a giant fibroadenoma complicated by a central infarct and an intra-lesional
      hemorrhage from a trauma to the breast. SUMMARY AND CONCLUSION: The complicated
      giant fibroadenoma with an intra-lesional hemorrhage has characteristics of both
      benign and malignant lesions, and is difficult to distinguish by history and
      physical alone. Ultrasonography is a valuable tool yet the core needle biopsy
      remains the gold standard to confirm the diagnosis.

PMID- 22980416
TI  - Delayed gastric perforation due to foreign-body ingestion.

PMID- 22980415
TI  - A comparison of the speed, success rate, and retention of rescue airway devices
      placed by first-responder emergency medical technicians: a high-fidelity human
      patient simulation study.
AB  - BACKGROUND: Current airway management for most first-responder basic emergency
      medical technicians (EMT-Bs) does not include the use of blind-advanced-airway
      devices. OBJECTIVE: To compare the speed, success rates, and skill retention with
      which EMT-Bs providers can place three blind-advanced-airway devices. METHODS:
      Prospective study of 43 EMT-Bs trained in the use of the Esophageal-Tracheal
      Combitube((r)) (ETC), King LT((r)) (KLT), and Laryngeal Mask Airway(TM) (LMA).
      The time it took each participant to place each device correctly and ventilate a
      human patient simulator was assessed. Primary outcome measures were the success
      rate of proper insertion for each device and time interval from initiation of
      mouth insertion to initiation of chest rise. To assess skill retention, at 3
      months the providers were reassessed under exact conditions. RESULTS: At Day 1,
      time required to place an ETC, LMA, and KLT were 32.7 +/- 12.3, 19.2 +/- 6.2, and
      20.1 +/- 6.6 s, respectively. Using paired t-tests, LMA and KLT were faster than
      ETC, p < 0.0001. At 3 months, pair-wise comparisons showed the ETC took longer to
      place than the KLT and LMA, p < 0.0001; and the LMA took longer to place than the
      KLT, p = 0.0034 (36.4 +/- 13.1 ETC, 24.8 +/- 12.4 LMA, 19.0 +/- 6.9 KLT). There
      was no statistical difference of failures in placing any device. CONCLUSIONS:
      Comparison of three rescue airway devices placed by EMT-Bs providers showed that
      it takes significantly longer to place an ETC compared to an LMA and KLT both on
      Day 1 and 3 months later. Three-month retention studies revealed that it took
      significantly longer to place an LMA compared to the KLT.

PMID- 22980417
TI  - Purple glove syndrome after intravenous phenytoin administration presenting in
      the emergency department.

PMID- 22980418
TI  - Application of next-generation sequencing in clinical oncology to advance
      personalized treatment of cancer.
AB  - With the development and improvement of new sequencing technology, next
      generation sequencing (NGS) has been applied increasingly in cancer genomics
      research over the past decade. More recently, NGS has been adopted in clinical
      oncology to advance personalized treatment of cancer. NGS is used to identify
      novel and rare cancer mutations, detect familial cancer mutation carriers, and
      provide molecular rationale for appropriate targeted therapy. Compared to
      traditional sequencing, NGS holds many advantages, such as the ability to fully
      sequence all types of mutations for a large number of genes (hundreds to
      thousands) in a single test at a relatively low cost. However, significant
      challenges, particularly with respect to the requirement for simpler assays, more
      flexible throughput, shorter turnaround time, and most importantly, easier data
      analysis and interpretation, will have to be overcome to translate NGS to the
      bedside of cancer patients. Overall, continuous dedication to apply NGS in
      clinical oncology practice will enable us to be one step closer to personalized
      medicine.

PMID- 22980420
TI  - Brain injury: refinement and restoration--the light is coming on.

PMID- 22980419
TI  - Favorable prognosis of female patients with nasopharyngeal carcinoma.
AB  - The female sex is traditionally considered a favorable prognostic factor for
      nasopharyngeal carcinoma (NPC). However, no particular study has reported this
      phenomenon. To explore the prognostic impact of gender on patients with NPC after
      definitive radiotherapy, we reviewed the clinical data of 2063 consecutive
      patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat
      sen University Cancer Center. The median follow-up for the whole series was 81
      months. The female and male patients with early stage disease comprised 49.4% and
      28.1% of the patient population, respectively. Both the 5-year overall survival
      (OS) and disease-specific survival (DSS) rates of female patients were
      significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001;
      DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the
      5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001)
      and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that
      gender, age, and TNM stage were independent prognostic factors for the 5-year OS
      and DSS of NPC patients. The favorable prognosis of female patients is not only
      attributed to the early diagnosis and treatment but might also be attributed to
      some intrinsic factors of female patients.

PMID- 22980421
TI  - Success of initial and repeated medial branch neurotomy for zygapophysial joint
      pain: a systematic review.
AB  - OBJECTIVES: To review the duration of pain relief after initial and repeated
      radiofrequency neurotomy (RFN) for cervical and lumbar zygapophysial joint pain.
      METHODS: We searched PubMed to identify all articles that met review criteria for
      in-depth analysis, synthesis, and review. RESULTS: Data from 16 articles are
      reported in this review, including 8 cervical studies, 7 lumbar studies, and 1
      study of both cervical and lumbar treatment. Overall, methodology and design
      quality of cervical studies exceeded that of lumbar studies. For initial cervical
      RFN, average range duration of >50% pain relief was 7.3-8.6 months. Repeated
      cervical RFN was successful 67%-95% of the time when the first RFN procedure was
      successful. When the first RFN procedure was unsuccessful, repeated RFN was
      successful 0%-67% of the time. The average range duration of pain relief after
      successful repeated RFN was 6.0-12.7 months. For initial lumbar RFN, the average
      duration of >50% pain relief was 9.0 months. Repeated lumbar RFN was successful
      33%-85% of the time when the first RFN procedure was successful. The average
      duration of pain relief after successful repeated lumbar RFN was 11.6 months.
      CONCLUSIONS: The results of this review indicate that pain relief after initial
      RFN generally ends after 7-9 months and that repeating RFN is likely to provide
      additional pain relief if initial RFN was successful. Results are similar between
      cervical and lumbar spine studies.

PMID- 22980422
TI  - Propensity scores: uses and limitations.

PMID- 22980423
TI  - Conus medullaris enterogenous cyst.

PMID- 22980424
TI  - Bilateral stylohyoid syndrome: a rare cause of cervical pain.

PMID- 22980425
TI  - Therapeutic advancement of chronic lymphocytic leukemia.
AB  - Despite the combinations of chemotherapy with monoclonal antibodies have further
      improved response rates, chronic lymphocytic leukemia (CLL) remains an incurable
      disease with an extremely variable course. This article reviews the ongoing
      clinical advances in the treatment of CLL in both previously untreated and
      relapsed disease and focuses on the benefit of different therapeutic strategies,
      the most effective therapy combinations and the potential activity of novel
      agents. Novel agents and combination therapies have been investigated by several
      studies in both the upfront and relapsed setting, particularly for patients with
      17p deletion, TP53 mutation and fludarabine-refractory CLL. While these agents
      and combination therapies have improved initial response rates, ongoing studies
      are continued to determine and improve the efficacy and safety. Despite
      advancements in the treatment of CLL have led to high response rates, allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) remains the only curative
      option and reduced-intensity conditioning (RIC) allo-HSCT must be strongly
      considered whenever feasible. As such, ongoing studies of these agents and other
      novel approaches in clinical development are needed to expand and improve
      treatment options for CLL patients.

PMID- 22980426
TI  - Short term effects of non-surgical periodontal treatment on gingival crevicular
      fluid levels of tissue plasminogen activator (t-PA) and plasminogen activator
      inhibitor 2 (PAI-2) in patients with chronic and aggressive periodontitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the gingival crevicular
      fluid (GCF) levels of tissue type plasminogen activator (t-PA) and plasminogen
      activator inhibitor 2 (PAI-2) in aggressive periodontitis (AgP), chronic
      periodontitis (CP) and periodontally healthy control subjects, before (BT) and
      after (AT) the non-surgical periodontal treatment. DESIGN: Systemically healthy
      12 CP and 13 AgP patients and 20 control subjects were included in this study.
      Plaque index, gingival index, probing depth and clinical attachment levels were
      recorded and GCF samples were collected BT and AT. Assays for GCF t-PA and PAI-2
      levels were carried out by an enzyme linked immunosorbent assay (ELISA). The
      chi(2), Wilcoxon and Mann-Whitney U tests and Spearman correlation coefficient
      were used for data analyses. RESULTS: Statistically significant reductions in
      clinical index scores were noted in both periodontitis groups after treatment. No
      significant differences were detected in GCF levels of t-PA and PAI-2 between CP
      and AgP groups at either BT or AT. There was a statistically significant decrease
      in GCF PAI-2 levels in CP after therapy (p<0.01). GCF t-PA levels in CP and AgP
      groups exhibited significant correlations with PD and CAL measurements at both BT
      and AT (p<0.01). CONCLUSION: Significant decrease was detected for GCF PAI-2
      levels in CP and clinical parameters in both CP and AgP by non-surgical
      periodontal treatment.

PMID- 22980427
TI  - Management of the second stage of labor.

PMID- 22980428
TI  - Planned home birth in economically developing countries: are we ready?

PMID- 22980429
TI  - Vaginal acidity enhancement with a 3% acetic acid gel prior to misoprostol
      treatment for pregnancy termination in the midtrimester.
AB  - OBJECTIVE: To investigate whether enhancing vaginal acidity improves the success
      of medical abortions in the midtrimester. METHODS: A double-blind, randomized,
      placebo-controlled trial was conducted with 48 women with missed midtrimester
      abortions. Twice daily, the study participants (n=24) were treated with a 3%
      acetic acid gel and the controls (n=24) with a placebo gel, starting 2 days prior
      to initiating the misoprostol treatment. The primary outcome measures were the
      rates of successful abortion within 24 and 48 hours. Secondary measures included
      gel tolerability and adverse effects of the misoprostol treatment. RESULTS: The
      success rates were higher in the study group, within both 24 hours (11/23 vs
      3/24; P=0.011) and 48 hours (18/23 vs 6/24; P<0.001). Among the women with a
      vaginal pH of 5 or higher at baseline, acidic gel was also associated with higher
      success rates within 24 hours (8/13 vs 2/15; P<0.01) and 48 hours (13/13 vs 3/15;
      P<0,001). The vaginal gels were well tolerated and the misoprostol treatment
      produced no serious adverse effects. CONCLUSION: A 3% acetic acid gel appears to
      be an effective and safe preparatory adjuvant to vaginal misoprostol treatment
      for midtrimester medical abortions, especially in women with a vaginal pH of 5 or
      higher. www.controlledtrials.com: ISRCTN75746444.

PMID- 22980430
TI  - Reduced postpartum hemorrhage after implementation of active management of the
      third stage of labor in rural Honduras.
AB  - OBJECTIVE: To assess outcomes after auxiliary nurses were trained and given
      resources to use active management of the third stage of labor (AMTSL) for all
      women giving birth in a low-resource, low-risk, rural, public birth center
      setting in northern rural Honduras. METHODS: Auxiliary nurses received training
      on estimation of blood loss before the preintervention phase of the study (July
      2004 through April 2005) and AMTSL, including use of intramuscular oxytocin, and
      estimation of blood loss prior to the intervention phase (July 2007 through June
      2008). Preintervention and intervention data on use of oxytocin, blood loss
      postpartum, hemorrhage rates, and management interventions were collected and
      compared. RESULTS: After nurses received training on AMTSL using intramuscular
      oxytocin, the use of intramuscular oxytocin during the third stage of labor
      increased from 63.8% to 96.5%. Postpartum hemorrhage rates decreased from 14.8%
      to 5.9% (P=0.001). Use of intrapartum oxytocin, which can have adverse effects,
      also increased: from 6.1% to 22.7% (P<0.001). CONCLUSION: Training auxiliary
      nurses to perform AMTSL using oxytocin in this birth center setting was effective
      in reducing the rate of postpartum hemorrhage; however, increased use of
      intrapartum oxytocin may be an unintended outcome of the increased accessibility
      of oxytocin.

PMID- 22980431
TI  - Misoprostol for the management of postpartum bleeding: a new approach.
AB  - Excessive postpartum hemorrhage (PPH) is a leading cause of maternal death
      globally. Current approaches to address PPH at the community level focus on
      reducing the incidence of PPH, but often fail to address the issue of PPH
      treatment. Given that institutional delivery is not yet a reality for all women,
      comprehensive care for excessive bleeding after delivery needs to be available at
      the community level. A new hybrid model of "secondary prevention"-presumptive
      treatment for women with more than average blood loss-presents one alternative
      community-based approach. If shown to be effective and feasible, this approach
      could support policy changes and avoid the need to provide uterotonics to all
      women after delivery. This Special Communication discusses some of the benefits
      and limitations of current community approaches using misoprostol for PPH
      prevention and explains why it is now opportune to translate clinical knowledge
      into pragmatic PPH service delivery strategies.

PMID- 22980432
TI  - Acceptability of cervical cancer screening via visual inspection with acetic acid
      or Lugol's iodine at Mulago Hospital, Uganda.
AB  - OBJECTIVE: To assess acceptability of cervical cancer screening via visual
      inspection with acetic acid or Lugol's iodine (VIA/VILI) at Mulago Hospital,
      Uganda. METHODS: Exit interviews were conducted among women who had undergone
      opportunistic screening by VIA/VILI at 2 family planning clinics based within the
      hospital. Measures of acceptability were willingness to undergo the procedure in
      future if required and willingness to recommend the procedure to others. Focus
      group discussions were conducted to determine reasons for declining VIA/VILI.
      RESULTS: A total of 384 participants were recruited into the study. Of the 229
      women who agreed to undergo screening by VIA/VILI, 209 (91.3%) were willing to
      recommend the service to other women, while 223 (97.4%) stated that they would
      undergo VIA/VILI again if the need arose. Education level showed a significant
      association with screening uptake (P=0.007). In all, 155 women declined
      screening. Reasons for refusal included fears about privacy, fear of pain or
      discomfort, and worry about the test results. CONCLUSION: Cervical cancer
      screening by VIA/VILI was rated highly acceptable among women who underwent the
      procedure. Women with a positive attitude toward screening could be trained as
      peer educators and community champions to improve uptake.

PMID- 22980433
TI  - Percutaneous coronary intervention via the radial artery: comparison of
      procedural success in emergency versus non-emergency cases.
AB  - BACKGROUND: STEMI and unstable acute coronary syndromes are associated with
      widespread adrenergic activation which may increase radial artery (RA) spasm,
      requiring cross-over to the femoral artery (FA) during percutaneous coronary
      intervention (PCI). We assessed the incidence of failed trans-radial artery PCI
      in emergency cases compared with non-emergency cases. METHODS: PCI procedures
      performed by default radial artery operators were assessed in our centre over a
      25 month period. Those who had both RA and FA access were identified to assess if
      the double punctures were elective or due to failure of the RA approach. Cross
      over rates were compared between emergency and non-emergency cases. RESULTS: 680
      cases of PCI were performed, 153 in an emergency setting. In non-emergency cases
      403/527 (76.5%) were performed via the RA. In the emergency setting 139/153
      (90.8%) were completed by the RA. Previous CABG with multiple arterial conduits
      was the most common reason for elective FA PCI in both groups. The RA to FA cross
      over rate was low with no significant difference between the emergency and non
      emergency groups (emergency 1.4%, non-emergency 1.2%, p=1.0). In both groups
      there was no significant difference between RA and FA procedures in terms of
      fluoroscopy times (emergency: mean 13.1 +/- 7.9 min vs 16.1 +/- 16.1 min, p=.25,
      non-emergency: 16.6 +/- 10.3 min vs 18.7 +/- 13.6 min, p=.07) or contrast volumes
      (emergency: mean 231 +/- 126 ml vs 229 +/- 102 ml, p=.77, non-emergency: 223 +/-
      85 ml vs 237 +/- 91 ml, p=.15). CONCLUSIONS: The vast majority of PCI can be
      successfully performed via the RA. Cross-over rates to the FA are low and are not
      more common in emergency patients.

PMID- 22980434
TI  - Negative lymph-node count is associated with survival in patients with resected
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: The number of recovered lymph nodes (LNs) is associated with the
      prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing
      surgical resection. A relationship between negative LN count and patient outcome
      has been demonstrated in gastrointestinal cancers, including colon and gastric
      cancers. However, little is known about the prognostic significance of negative
      LN counts in ESCC. METHODS: In this retrospective study we examined patient
      survival in relation to negative LN count in 252 patients with surgically
      resected ESCC. Cox proportional hazards models were used to compute hazard ratios
      (HRs) for death, adjusted for clinical and pathological characteristics. RESULTS:
      Negative LN count was associated with year of operation (P = .0015) and number of
      fields dissected (P < .0001) but not with tumor location, TNM (ie, tumor, node,
      metastasis) stage, N status, or histologic grade. Patients with >= 31 negative
      LNs experienced a reduction in overall mortality compared with those with 0-30
      negative LNs (log-rank P = .0042; univariate HR = 0.48, 95% confidence interval
      0.28-0.79, P = .0035; multivariate HR = 0.41, 95% confidence interval 0.21-0.76,
      P = .0039). The influence of negative LN count on overall survival was modified
      by the number of fields dissected (P for interaction = .033); more negative LNs
      were significantly associated with lower overall mortality in three-field
      dissection (log rank P < .0001) but not in two-field dissection (log rank P =
      .93). CONCLUSION: A negative LN count was associated with improved survival in
      patients with curatively resected ESCC.

PMID- 22980435
TI  - Scar perceptions after thyroid and parathyroid surgery: comparison of minimal and
      conventional approaches.
AB  - BACKGROUND: An incision less than 3 cm in length in the neck is the main feature
      that discriminates the minimally invasive thyroidectomy and parathyroidectomy
      from traditional procedures. Smaller neck scars are assumed to yield better
      patient satisfaction, although no established data support this. In this
      analysis, we evaluated the satisfaction of patients who had undergone both
      procedures, while examining the effects of sociodemographic and surgical
      characteristics. METHODS: We analyzed data from 691 patients who underwent a
      thyroidectomy or parathyroidectomy between January 2000 and March 2010. We
      assessed the satisfaction of patients who underwent conventional compared to
      minimally invasive procedures, using the validated Patient Scar Assessment
      Questionnaire (PSAQ). We included both the appearance and the consciousness
      subscales. RESULTS: Overall, patients were satisfied with their neck scars, as
      indicated by the low scores in appearance (13.3; range, 9 to 31) and
      consciousness (8.5; range, 6 to 24) subscales. The degree of satisfaction
      improved with increased time since surgery (P < .001). Patient satisfaction was
      similar regardless of the procedure used, implying that smaller scars do not
      provide better patient satisfaction. Most patients (81.2%) reported that they
      would not have preferred a transaxillary procedure over the procedure they
      received. CONCLUSION: A smaller incision in the neck was not associated with
      better patient satisfaction. New surgical approaches aimed at maximizing cosmesis
      while minimizing scar size should be evaluated for cost-effectiveness and
      clinical outcomes, as well as patient satisfaction, before becoming the standard
      of care.

PMID- 22980436
TI  - Physiological status alters immunological regulation of bovine follicle
      differentiation in dairy cattle.
AB  - Lactation in dairy cattle is associated with a multitude of endocrine, metabolic
      and immunological changes that not only influence animal health, but also affect
      fertility, and in particular ovarian function. We have previously generated a
      global transcriptomic profile of bovine follicular tissue using RNA sequencing.
      This study aimed to: identify key immune-related transcriptional changes that
      occur during follicle differentiation and luteinisation using ingenuity pathway
      analysis (IPA); and determine if a compromised model of stress (i.e. lactation)
      influences the temporal expression of these genes. Ovarian follicular tissue from
      Holstein-Friesian non-lactating heifers (n=17) and lactating cows (n=16) was
      compared at three stages of preovulatory follicle development: (A) the newly
      selected dominant follicle in the luteal phase (Selection); (B) the follicular
      phase before the LH surge (Differentiation), and (C) the preovulatory phase after
      the LH surge (Luteinisation). IPA revealed an over-representation of immune
      related pathways in theca compared with granulosa cells during differentiation;
      these were related to leucocyte extravasation and chemotaxis. Conversely,
      luteinisation was characterised by over-representation of immune-related pathways
      in granulosa compared with theca cells; these were related to inflammation and
      innate immune response. Notably, comparison of follicles from heifers and
      lactating cows revealed a large number of differentially expressed genes
      associated with immune cell subpopulations and chemotaxis. In conclusion,
      identification of immune-related canonical pathways during follicle development
      supports the hypothesis that ovulation is an inflammatory event. This process is
      influenced by the physiological status of lactation and likely contributes to
      compromised peri-ovulatory follicle function by impairing the inflammatory
      process of ovulation.

PMID- 22980439
TI  - [Iron deficiency in children and teenagers: a health problem that is still
      present].
AB  - Iron deficiency remains a problem in developing countries as well as in
      industrial nations. The prevalence of iron deficiency in children under 5 years
      of age is identical in Europe and the USA, and is in the order of 7 to 9% on
      average with an anaemia prevalence of 2.3%. The major cause is dietary
      deficiency, particularly in premature babies, infants, teenagers, and children in
      unstable situations. It is important to prevent the development of anaemia,
      especially in infants, due to its morbid consequences particularly with respect
      to development. Screening and simple preventative measures (iron supplements and
      dietary advice) need to be systematically set up, particularly in at-risk
      populations, and are detailed in the present article.

PMID- 22980437
TI  - Differences in dietary intakes, food sources and determinants of total flavonoids
      between Mediterranean and non-Mediterranean countries participating in the
      European Prospective Investigation into Cancer and Nutrition (EPIC) study.
AB  - A greater adherence to the traditional Mediterranean (MED) diet is associated
      with a reduced risk of developing chronic diseases. This dietary pattern is based
      on higher consumption of plant products that are rich in flavonoids. We compared
      the total flavonoid dietary intakes, their food sources and various lifestyle
      factors between MED and non-MED countries participating in the EPIC study.
      Flavonoid intakes and their food sources for 35,628 subjects, aged 35-74 years
      and recruited between 1992 and 2000, in twenty-six study centres were estimated
      using standardised 24 h dietary recall software (EPIC-Soft(r)). An ad hoc food
      composition database on flavonoids was compiled using analytical data from the
      United States Department of Agriculture and Phenol-Explorer databases. Moreover,
      it was expanded to include using recipes, estimations of missing values and
      flavonoid retention factors. No significant differences in total flavonoid mean
      intake between non-MED countries (373.7 mg/d) and MED countries (370.2 mg/d) were
      observed. In the non-MED region, the main contributors were proanthocyanidins
      (48.2%) and flavan-3-ol monomers (24.9%) and the principal food sources were tea
      (25.7%) and fruits (32.8%). In the MED region, proanthocyanidins (59.0%) were by
      far the most abundant contributor and fruits (55.1%), wines (16.7%) and tea
      (6.8%) were the main food sources. The present study shows similar results for
      total dietary flavonoid intakes, but significant differences in flavonoid class
      intakes, food sources and some characteristics between MED and non-MED countries.
      These differences should be considered in studies about the relationships between
      flavonoid intake and chronic diseases.

PMID- 22980441
TI  - Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic
      anhydrase IX monoclonal antibody girentuximab in patients with advanced renal
      cell carcinoma.
AB  - BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC) have
      a dismal prognosis. Therefore, new and less toxic treatments are needed.
      OBJECTIVE: We determined the maximum tolerated dose (MTD) and potential
      therapeutic efficacy of multiple infusions of lutetium 177 ((177)Lu)-girentuximab
      (cG250) on various dose levels in a phase 1 trial in patients with progressive
      metastasized ccRCC. DESIGN, SETTING, AND PARTICIPANTS: In this uncontrolled case
      series in 23 patients with progressive ccRCC metastases, cG250 accumulation was
      verified by diagnostic indium 111-cG250 imaging. Patients then received a high
      activity dose of (177)Lu-cG250. INTERVENTION: Groups of three patients received
      (177)Lu-cG250, starting at a dose level of 1110 MBq/m(2)(177)Lu-cG250, with dose
      increments of 370 MBq/m(2) per group. In the absence of persistent toxicity,
      progressive disease, and accelerated blood clearance, patients were eligible for
      retreatment after 3 mo with 75% of the previous activity dose. Patients could
      receive a total of three treatment cycles. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Determination of the MTD was the primary and therapeutic efficacy was
      the secondary outcome measurement of the study. RESULTS AND LIMITATIONS: The MTD
      was 2405 MBq/m(2) because higher doses resulted in dose-limiting myelotoxicity.
      Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%])
      treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo
      after the first treatment, and one patient showed a partial response that lasted
      for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95%
      confidence interval [CI], +/- 17.0) during the last 3 mo before study entry to
      5.5% (95% CI, +/- 5.3; p<0.001) at 3 mo after the first treatment cycle. No major
      nonhematologic side effects were observed. CONCLUSIONS: (177)Lu-cG250
      radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity
      dose level as high as 2405 MBq/m(2) (MTD). Radioimmunotherapy with (177)Lu-cG250
      may stabilize previously progressive metastatic ccRCC.

PMID- 22980442
TI  - Smoking reduces the efficacy of intravesical bacillus Calmette-Guerin
      immunotherapy in non-muscle-invasive bladder cancer.

PMID- 22980443
TI  - Outcome following active surveillance of men with screen-detected prostate
      cancer. Results from the Goteborg randomised population-based prostate cancer
      screening trial.
AB  - BACKGROUND: Active surveillance (AS) has emerged as a treatment strategy for
      reducing overtreatment of screen-detected, low-risk prostate cancer (PCa).
      OBJECTIVE: To assess outcomes following AS of men with screen-detected PCa.
      DESIGN, SETTING, AND PARTICIPANTS: Of the 968 men who were diagnosed with screen
      detected PCa between 1995 and 2010 in the Goteborg randomised, population-based
      PCa screening trial, 439 were managed with AS and were included in this study.
      Median age at diagnosis was 65.4 yr of age, and median follow-up was 6.0 yr from
      diagnosis. INTERVENTION: The study participants were followed at intervals of 3
      12 mo and were recommended to switch to deferred active treatment in case of a
      progression in prostate-specific antigen, grade, or stage. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: The end points-overall survival (OS), treatment-free
      survival, failure-free (no relapse after radical treatment) survival, and cancer
      specific survival-were calculated for various risk groups (very low, low,
      intermediate, and high) with Kaplan-Meier estimates. A Cox proportional hazards
      model as well as a competing risk analysis were used to assess whether risk group
      or age at diagnosis was associated with failure after AS. RESULTS AND
      LIMITATIONS: Forty-five per cent of all screen-detected PCa were managed with AS,
      and very low-risk and low-risk PCa constituted 60% of all screen-detected PCa.
      Thirty-seven per cent (162 of 439) switched from surveillance to deferred active
      treatment, and 39 men failed AS. The 10-yr OS, treatment-free survival, and
      failure-free survival were 81.1%, 45.4%, and 86.4%, respectively (Kaplan-Meier
      estimates). Men with low-, intermediate-, and high-risk tumours had a hazard
      ratio for failure of 2.1 (p=0.09), 3.6 (p=0.002), and 4.6 (p=0.15), respectively,
      compared to very low-risk tumours (Cox regression). Only one PCa death occurred,
      and one patient developed metastasis (both in the intermediate-risk group). The
      main limitation of this study is the relatively short follow-up. CONCLUSIONS: A
      large proportion of men with screen-detected PCa can be managed with AS. AS
      appears safe for men with low-risk PCa.

PMID- 22980444
TI  - Evaluation of the efficacy of oxytetracycline treatment followed by vaccination
      against Q fever in a highly infected sheep flock.
AB  - The aim of this research was to evaluate the efficacy of oxytetracycline
      treatment following an outbreak of Q fever in a sheep flock when gestation is too
      advanced for vaccination to be used. In such cases, immediate application of
      antibiotics is needed and vaccination postponed until the next breeding season.
      Seventy-five per cent of ewes from a dairy sheep flock affected by Q fever were
      treated with oxytetracycline at approximately days 100 and 120 of gestation, with
      the remaining 25% of the animals kept as untreated controls. Vaginal swabs,
      faeces and milk samples from 81 ewes (57 treated, 24 untreated) were analysed by
      PCR within 30 days of lambing and revealed a high percentage of Coxiella burnetii
      shedders. No significant differences were found between groups in either the
      percentage of shedders or in the mean amount of bacteria shed. In the following
      season 75% of the ewes and 50% of the replacement ewe lambs were vaccinated with
      a phase I vaccine prior to artificial insemination. Both vaccinated and control
      groups were homogeneously composed of ewes treated and untreated with antibiotics
      in the previous season. The number of shedders and the bacterial excretion load
      decreased significantly compared to the previous season but no statistically
      significant differences were found between vaccinated and control groups. In
      addition, no significant effect derived from the application of oxytetracycline
      in the previous season was observed. Vaccination was repeated for the following
      two seasons, and the percentage of animal shedders was reduced to minimal levels
      highlighting the importance of vaccination over the longer term.

PMID- 22980445
TI  - Prediction of motor responses to surgical stimuli during bilateral orchiectomy of
      pigs using nociceptive flexion reflexes and the bispectral index derived from the
      electroencephalogram.
AB  - Movement responses to noxious stimuli during anaesthesia indicate nociception.
      Under experimental conditions consistent prediction of such movement responses
      has been achieved by the use of nociceptive flexion reflexes (NFRs). The aim of
      this study was to investigate the reliability of NFRs and the
      electroencephalogram bispectral index (BIS) in predicting motor responses to real
      surgical stimuli in pigs. The study was undertaken in 30 pigs undergoing
      bilateral orchiectomy under ketamine/azaperone anaesthesia. During the operation,
      movement responses to seven distinct surgical steps that provided noxious stimuli
      of different intensity were evaluated. Any movement response of limbs or the head
      was considered as a positive response. For each surgical step the values of NFRs
      and the BIS obtained just prior to the step were tested as predictors of movement
      responses. The prediction probability for movement responses was 0.58+/-0.04 for
      the BIS and 0.76+/-0.03 for the NFRs. It was concluded that NFRs but not the BIS
      can predict the effectiveness of ketamine anaesthesia in terms of the suppression
      of movement responses to surgical stimuli.

PMID- 22980446
TI  - Care of the injured worldwide: trauma still the neglected disease of modern
      society.
AB  - Traditionally, surgical diseases including emergency and injury care have
      garnered less attention and support internationally when compared to other
      medical specialties. Over the past decade however, healthcare professionals have
      increasingly advocated for the need to address the global burden of non
      communicable diseases. Surgical disease, including traumatic injury, is among the
      top causes of death and disability worldwide and the subsequent economic burden
      is substantial, falling disproportionately on low- and middle-income countries
      (LMICs). The future of global health in these regions depends on a redirection of
      attention to diseases managed within surgical, anesthesia and emergency
      specialties. Increasing awareness of these disparities, as well as increasing
      focus in the realms of policy and advocacy, is crucial. While the barriers to
      providing quality trauma and emergency care worldwide are not insurmountable, we
      must work together across disciplines and across boundaries in order to negotiate
      change and reduce the global burden of surgical disease.

PMID- 22980447
TI  - Prognostic impact of serum 25-hydroxivitamin D [25(OH)D] concentrations in
      patients with lymphoid malignancies.
AB  - The incidence of lymphoid malignancies has been increasing rapidly. Despite
      growing evidence for a relationship between serum 25-hydroxivitamin D [25(OH)D]
      concentrations and solid tumor risk, far less is known about the relationship
      between 25(OH)D and the risk of hematologic malignancy.  This study aimed to
      assess the prognostic relevance of serum 25(OH)D concentrations in patients with
      B chronic lymphocytic leukemia (B-CLL) and non Hodgkin's lymphoma (NHL). The
      study was carried out on 195 newly diagnosed patients (75 B-CLL and 120 NHL) as
      well as 30 normal healthy controls.  For all patients and normal controls serum
      25(OH)D concentrations were assayed by enzyme-linked immunosorbent assay. Serum
      25(OH)D levels were significantly lower in B-CLL and NHL patients as compared
      with normal controls (P = 0.00 for both). Also, there are significant
      associations  between serum 25(OH)D levels and positive CD 38, positive ZAP 70 as
      well as Binet stages (chi(2) = 16.071, 16.644, 21.134 respectively; P = 0.00 for
      all) in the B-CLL patient group. Moreover, there are significant associations
      between serum 25(OH)D status  and international prognostic index (IPI),
      performance status (chi(2) = 6.994, 9.212, P = 0.02, 0.01 respectively), but not
      with clinical stages (chi(2) = 3.115, P = 0.539) in NHL. Multivariate analysis
      revealed that  25(OH)D insufficiency is an independent poor prognostic factor in
      both B-CLL and NHL patient groups. In conclusion, 25(OH)D insufficiency is an
      independent poor prognostic factor in patients with B-CLL and NHL. 25(OH)D might
      be a therapeutic target in lymphoid malignancies.

PMID- 22980448
TI  - Predicting success and failure in juvenile drug treatment court: a meta-analytic
      review.
AB  - This meta-analysis summarizes 41 studies that examined associations between
      characteristics of adolescent participants in juvenile drug treatment court and
      outcomes (i.e., premature termination, recidivism). A summary of within- and post
      program recidivism rates was calculated, as was a global estimate of the
      premature drop-out rate. One clear trend in the available studies was the
      dramatic difference in recidivism rates for adolescents who succeed in graduating
      from drug court, relative to those who do not. In addition, the review revealed
      that behavior patterns evidenced during drug court participation were most
      strongly associated with both the probability of graduating successfully from
      drug court and recidivism (e.g., few in-program arrests, citations, detentions,
      and referrals; greater length of time in program or amount of treatment; lower
      use of drug and alcohol use, few positive urine screens, greater school
      attendance). Unfortunately, non-white participants tend to have a lower
      probability of graduation from drug court and experience higher recidivism during
      and following the program. Available juvenile drug treatment court studies
      confirm a number of reputed adolescent risk factors associated with substance
      abuse, criminality, treatment failure, and recidivism among adolescents (e.g.,
      higher levels of emotional and behavioral problems, higher levels and severity of
      pre-program substance abuse, male gender). Suggestions for improving the effects
      of juvenile drug treatment court based on key results of the meta-analysis are
      offered.

PMID- 22980449
TI  - Prescription opioid abuse, chronic pain, and primary care: a Co-occurring
      Disorders Clinic in the chronic disease model.
AB  - Abuse of opioids has become a public health crisis. The historic separation
      between the addiction and pain communities and a lack of training in medical
      education have made treatment difficult to provide, especially in primary care.
      The Co-occurring Disorders Clinic (COD) was established to treat patients with co
      morbid chronic pain and addiction. This retrospective chart review reports
      results of a quality improvement project using buprenorphine/naloxone to treat co
      occurring chronic non-cancer pain (CNCP) and opioid dependence in a primary care
      setting. Data were collected for 143 patients who were induced with
      buprenorphine/naloxone (BUP/NLX) between June 2009 and November 2011. Ninety
      three patients (65%) continued to be maintained on the medication and seven
      completed treatment and were no longer taking any opioid (5%). Pain scores showed
      a modest, but statistically significant improvement on BUP/NLX, which was
      contrary to our expectations and may be an important factor in treatment
      retention for this challenging population.

PMID- 22980451
TI  - Spatiotemporal chaos in Easter Island ecology.
AB  - This paper demonstrates that a recently proposed spatiotemporal model for  the
      ecology of Easter Island admits periodic and chaotic attractors, not previously 
      reported. Such behavior may more realistically depict the population dynamics of 
      general ecosystems and illustrates the power of simple models to produce the kind
      of complex behavior that is ubiquitous in such systems.

PMID- 22980450
TI  - Opioid overdose prevention with intranasal naloxone among people who take
      methadone.
AB  - Overdose education and naloxone distribution (OEND) is an intervention that
      addresses overdose, but has not been studied among people who take methadone, a
      drug involved in increasing numbers of overdoses. This study describes the
      implementation of OEND among people taking methadone in the previous 30 days in
      various settings in Massachusetts. From 2008 to 2010, 1553 participants received
      OEND who had taken methadone in the past 30 days. Settings included inpatient
      detoxification (47%), HIV prevention programs (25%), methadone maintenance
      treatment programs (MMTP) (17%), and other settings (11%). Previous overdose,
      recent inpatient detoxification and incarceration, and polysubstance use were
      overdose risks factors common among all groups. Participants reported 92 overdose
      rescues. OEND programs are public health interventions that address overdose risk
      among people who take methadone and their social networks. OEND programs can be
      implemented in MMTPs, detoxification programs, and HIV prevention programs.

PMID- 22980452
TI  - Capturing and quantifying the dynamics of valenced emotions and valenced events
      of the organism-environment system.
AB  - The events we encounter and the emotions we experience are valenced-they  are
      positively or negatively charged. Although these occurrences seem to be
      distributed  irregularly throughout the day, the two experiments presented here
      reveal systematicity  in the temporal dynamics of affective experience using a
      variety of time-series analyses.  In Experiment 1, participants used a portable
      button to respond to event valence  (the positive or negative charge of an event
      in the environment) or affective valence  (one's positive or negative feeling at
      the time of responding). This methodology yields  signed response durations,
      indexing the valence and intensity of an occurrence, and inter-response 
      intervals, indexing their distribution. These measures revealed that valenced
      occurrences are  correlated with both temporally proximal and remote occurrences.
      Experiment 2 validated the  methodology employed in Experiment 1 using
      artificial, laboratory-created event structures.  Implications of dynamical
      approaches to understanding emotion are discussed.

PMID- 22980453
TI  - Nonlinear bifurcations of psychological stress negotiation: new properties of a
      formal dynamical model.
AB  - Dynamical systems analysis is applied to a nonlinear model of stress and  coping
      (Neufeld, 1999).  The model is composed of 6  order parameters and 11   control
      parameters, and  integrates core constructs of the topic domain, including 
      variants of cognitive appraisal, differential stress susceptibility, stress
      activation,  and coping propensity. In part owing to recent advances in 
      Competitive Modes Theory (Yao, Yu & Essex, 2002), previously intractable but
      substantively  significant dynamical properties of the 6-dimensional model are
      identified. They include  stable and unstable fixed-point equilibria (higher
      dimensional saddle-node bifurcation),  oscillatory patterns attending fixed-point
      de-stabilization, and chaotic behaviors.  Examination of the nature of system
      fixed-point de-stabilization, in relation to its  control parameters, unveils
      mechanisms of re-stabilization, and dynamic stability control.  All identified
      dynamics emerge naturally from a system whose construction guideposts are  lodged
      in the addressed content domain. Dynamical complexities therefore may be
      intrinsic  to the present content domain, possibly no less so than in other
      disciplines where the  presence of such attributes has been established.

PMID- 22980454
TI  - Mathematical models of panic disorder.
AB  - The dynamics of panic attacks in both functional individuals and panic disorder 
      patients are qualitatively evaluated by using coupled nonlinear differential
      equations.  Each panic attack is described by two variables, fear and physical
      symptoms. Different thresholds  for these variables are defined for functional
      individuals, patients in the acute phase, and  patients in the chronic phase.
      Integral lines, vector fields, and time series of solutions,  based on the
      proposed coupled nonlinear differential equations, are shown. The efficacy of 
      treatment and severity of each panic attack are also evaluated. Under our
      hypothesized condition,  it is shown that particular pharmacological treatment
      could change the final states of patients  in the acute phase, but could not
      change either the final states of patients in the chronic phase  or those of
      functional individuals. Our model is consistent with the well-known major
      features of  panic attacks, and sheds new light on the dynamics of panic attacks.

PMID- 22980455
TI  - New paradigm for task switching strategies while performing multiple tasks:
      entropy and symbolic dynamics analysis of voluntary patterns.
AB  - It has become well established in laboratory experiments that switching tasks, 
      perhaps due to interruptions at work, incur costs in response time to complete
      the next task.  Conditions are also known that exaggerate or lessen the switching
      costs. Although switching  costs can contribute to fatigue, task switching can
      also be an adaptive response to fatigue.  The present study introduces a new
      research paradigm for studying the emergence of voluntary  task switching
      regimes, self-organizing processes therein, and the possibly conflicting roles 
      of switching costs and minimum entropy. Fifty-four undergraduates performed 7
      different computer-based  cognitive tasks producing sets of 49 responses under
      instructional conditions requiring task quotas  or no quotas. The sequences of
      task choices were analyzed using orbital decomposition to  extract pattern types
      and lengths, which were then classified and compared with regard to  Shannon
      entropy, topological entropy, number of task switches involved, and overall
      performance.  Results indicated that similar but different patterns were
      generated under the  two instructional conditions, and better performance was
      associated with lower topological entropy.  Both entropy metrics were associated
      with the amount of voluntary task switching.  Future research should explore
      conditions affecting the trade-off between switching costs and entropy,  levels
      of automaticity between task elements, and the role of voluntary switching
      regimes on fatigue.

PMID- 22980456
TI  - DNA mismatch repair: Dr. Jekyll and Mr. Hyde?
AB  - In this issue, Pena-Diaz et al. (2012) describe a pathway for somatic mutation in
      nonlymphoid cells termed noncanonical DNA mismatch repair, whereby the error
      prone translesion polymerase Pol-eta substitutes for high-fidelity replicative
      polymerases to resynthesize excised regions opposite DNA damage.

PMID- 22980457
TI  - Janus-faced PIDD: a sensor for DNA damage-induced cell death or survival?
AB  - In this issue of Molecular Cell, an activator of the PIDDosome (a complex
      comprising of PIDD, RAIDD, and caspase-2) is described in experiments detailing
      endogenous PIDDosome assembly and caspase-2 function after DNA damage in the
      presence of Chk1 suppression (Ando et al., 2012).

PMID- 22980458
TI  - [Not Available].

PMID- 22980460
TI  - Vasodilator effect of ghrelin in the rat aorta.
AB  - BACKGROUND AND OBJECTIVE: Ghrelin is a hormone mainly produced by the stomach and
      has been identified as the natural ligand of the growth hormone secretagogue
      receptor (GHS-R). In addition to its orexigenic effect, ghrelin modulates
      homeostasis of the cardiovascular system. The aim of this study was to analyze
      the effect of ghrelin on the vascular reactivity of the aorta. MATERIAL AND
      METHODS: This study was performed in the thoracic aorta of 10-12- week-old male
      Wistar rats. Passive wall tension and contractile responses to angiotensin II
      (Ang II) (10(-7) mol/l) in the presence of ghrelin (10(-8) mol/l) were evaluated
      using the organ bath system. The presence of the functional ghrelin receptor, GHS
      R 1a, in vascular smooth muscle cells (VSMCs) of the aorta was determined by
      Western blot. RESULTS: VSMCs of the vascular wall of the aorta expressed the GHS
      R 1a protein. Incubation of the intact aorta with ghrelin (10(-8) mol/l) induced
      a reduction (p<0.01) in passive wall tension. In endotheliumdenuded aorta,
      ghrelin did not modify basal vasomotor tone. However, incubation of endothelium
      denuded aorta with ghrelin inhibited (p<0.01) Ang II (10(-7) mol/l)-induced
      vasoconstriction. CONCLUSIONS: Ghrelin exerts an endothelium-dependent and 
      independent depressor action on aortic vascular reactivity. These findings
      provide additional information on the physiological effect of ghrelin on arterial
      pressure regulation.

PMID- 22980459
TI  - Can the metabolic control targets established for patients with type 1 diabetes
      be achieved in clinical practice?
AB  - OBJECTIVE: To evaluate the quality of healthcare in patients with type 1 diabetes
      attended in the Endocrinology and Clinical Nutrition Unit of the Hospital Puerta
      del Mar in Cadiz (Spain). METHODOLOGY: : The database included in the computer
      application HP-Doctor used for all patients attended in our unit (admissions,
      consultations and peripheral centers) was analyzed. All patients with a principal
      or secondary diagnosis of type 1 diabetes were included. The quality indicators
      analyzed were selected from the main clinical practice guidelines for these
      patients. RESULTS: A large cohort of patients with type 1 diabetes (n=489)
      followed-up from 2005 to 2007 was analyzed. During the study period, the mean
      glycated hemoglobin level (HbA(1c)) decreased from 7.78% to 7.36%, the percentage
      of patients with HbA(1c) lower than 7% increased from 24.6% to 27.1% and the
      percentage patients with a mean HbA(1c) of more than 8% decreased from 42.6% to
      38.7%. In 2007, only 35.5% of patients maintained low-density lipoprotein
      concentrations of less than 100 mg/dl. CONCLUSIONS: Despite the improvement
      obtained in metabolic control parameters, most of the patients with type 1
      diabetes studied showed inadequate glycemic and lipid control.

PMID- 22980461
TI  - Diabetes mellitus in young immigrants from hindustan. A descriptive study.
AB  - AIM: To analyze the physiological and clinical characteristics of diabetes
      mellitus (DM) in young immigrants from Hindustan. MATERIAL AND METHODS: We
      performed a descriptive analysis of clinical and laboratory variables related to
      DM in diabetic Hindustanis aged between 15 and 40 years old. Body mass index
      (BMI) and waist perimeter (WP) were calculated. The immunology of DM and baseline
      C-peptide were studied and insulin resistance (IR) was determined by Homeostasis
      Model Assessment: Insulin Resistance (HOMA-IR). RESULTS: The final sample
      consisted of 30 patients. The prevalence of DM was 0.84%. All patients had DM2
      and 50% had high IR. Baseline C-peptide secretion was preserved in all patients.
      The cut-off points that best predicted IR in this ethnic group were a BMI higher
      than 25 and a WC of more than 95 cm. CONCLUSIONS: Most young Hindustani
      immigrants with diabetes have DM2 with preserved baseline insulin secretion and
      IR. Lower degrees of obesity than in the Spanish population were associated with
      IR.

PMID- 22980462
TI  - Diabetic retinopathy and blindness in Spain: epidemiology and prevention.
AB  - Diabetic retinopathy (DR) remains an important cause of blindness in Spain. The
      prevalence of blindness in diabetic persons ranges from 4% to 11% and is higher
      than that in other countries (between 1 and 5%). The prevalence of DR in Spain
      varies in the distinct studies but is approximately 40%, while that of
      proliferative DR is between 4% and 6% and that of macular edema is between 1.4 %
      and 7.9%. Routine screening is effective in reducing the incidence of visual loss
      and blindness. Screening compliance is about 50% in primary care and is over 70%
      in specialized care. Although there is some evidence that the incidence of DR is
      decreasing in Europe and the USA, only a few studies have reported the same trend
      in Spain. Screening of DR with nonmydriatic camera has been supported by several
      guidelines, since this procedure shows the best cost-effectiveness ratio and is
      easy to use.

PMID- 22980463
TI  - Genetics of pseudohypoparathyroidism: bases for proper genetic counselling.
AB  - Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and
      hyperphosphatemia due to resistance to parathyroid hormone (PTH). Patients with
      PHP-Ia often show additional hormone resistance and characteristic physical
      features that are collectively termed Albright's hereditary osteodystrophy (AHO).
      These features are also present in pseudopseudohypoparathyroidism (PPHP), but
      patients with this disorder do not show hormone resistance. PHP-Ib patients, on
      the other hand, predominantly show renal PTH resistance and lack features of AHO.
      From the genetic point of view, PHP-I is caused by defects in the GNAS gene or in
      the 5' region of this gene locus. PHP-Ia is caused by heterozygous inactivating
      mutations in any of the 13 exons codifying the alpha subunit of the stimulatory
      guanine nucleotide-binding protein (Gsalpha), while PHP-Ib is due to alterations
      in the methylation pattern of the 5' regions of the locus, usually associated
      with upstream microdeletions that are maternally transmitted. The imprinting
      pattern that affects the GNAS locus has important implications for the
      inheritance pattern and consequently for appropriate genetic counselling.

PMID- 22980464
TI  - Spanish growth studies 2008. New anthropometric standards.
AB  - Cross-sectional and longitudinal growth studies have recently been conducted in
      Spain. These studies have allowed neonatal anthropometry in premature and term
      neonates and postnatal growth in children and adolescents to be evaluated.
      Moreover, a longitudinal study that allows pubertal growth to be evaluated for
      distinct groups according to maturation has also been published. Between 1999 and
      2002, birth weight and vertex-heel length were evaluated in 9,362 newborns (4,884
      boys and 4,478 girls), with a gestational age of 26-42 weeks. An increase in
      these values compared with previous Spanish studies (1987-1992) and sexual
      dimorphism were observed. Between 2000 and 2004, height, weight and body mass
      index (BMI) were evaluated in 32,064 individuals (16,607 males, 15,457 females)
      aged 0-24 years. An increasing secular trend was observed compared with data
      obtained 20 years previously. Increases in BMI exceeded those in height for BMI
      values above the 50th percentile. A longitudinal growth study of 458 healthy
      individuals (223 boys, 235 girls) born between 1978 and 1982 yielded pubertal
      growth and maturity standards for each of the five pubertal maturity groups. In
      addition, data on skinfolds, bone mass and intellectual development from birth to
      adulthood were also provided. Adult height in both studies was similar to that
      reported by European and American studies, but was lower than that reported for
      German, Swedish and Dutch populations. In males, BMI was higher than in other
      European populations and was close to that of the US population. In females, BMI
      was similar to that in European populations and was lower than that in the US
      population.

PMID- 22980465
TI  - Occult secretion of acth and bilateral adrenalectomy: sometimes the messenger has
      to be shot.
AB  - Cushing's syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion
      is infrequent, the most frequent cause being bronchial carcinoid; nevertheless,
      in a considerable proportion of cases (up to 16%), the origin of ACTH secretion
      is not found. Treatment of Cushing's syndrome due to ectopic ACTH secretion is
      surgical resection of the tumor. However, surgical excision is not always
      feasible, either because the tumor has not been located, or because it is
      unresectable; in these cases the question is when to carry out a bilateral
      adrenalectomy. We present a case of ACTH-dependent hypercortisolism, in which the
      ectopic origin of ACTH secretion was established from the results of
      complementary tests (suppression tests, petrosal sinus sampling, imaging);
      nevertheless, none of the imaging tests was able to identify the secreting tumor.
      Consequently, after a reasonable interval, a bilateral adrenalectomy was
      performed, with good clinical results.

PMID- 22980466
TI  - An unusual association: pheochromocytoma on an atrophied adrenal gland due to
      addison's disease.
AB  - Autoimmune polyendocrine syndrome type II (APS-II) is the most common
      immunoendocrinopathy syndrome. APS-II is defined by the development of two or
      more of the following entities: primary adrenal insufficiency (Addison's
      disease), Graves' disease, type 1A diabetes mellitus, autoimmune thyroiditis,
      primary hypogonadism, celiac disease, and myasthenia gravis. Other frequent
      clinical findings are vitiligo, alopecia, pernicious anemia and/or serositis.
      Primary adrenal insufficiency in these patients affects the adrenal cortex, which
      is destroyed by autoantibodies against 21-hydroxylase. Unlike other causes of
      adrenal insufficiency (infectious diseases, infiltrative diseases, bleeding,
      tumors), the adrenal medulla is not involved. Pheochromocytomas are tumors
      arising from the chromaffin cells of the sympathetic nervous system in the
      adrenal medulla. The clinical symptoms of these tumors vary from isolated
      hypertension or hypertension accompanied by paroxysmal episodes -including the
      classical triad of headache, palpitations and diaphoresis-to potentially serious
      manifestations such as acute pulmonary edema, arrhythmias and sudden death.
      Nevertheless, up to 40% of affected patients are asymptomatic. We present the
      case of a patient diagnosed with APS-II who developed a pheochromocytoma. In this
      patient, the adrenal gland cortex was atrophied and the tumor was attached to the
      adrenal medulla. This coexistence of endocrinopathies, with no etiologic
      connection, is a surprising finding, which has not previously been described in
      the current literature.

PMID- 22980467
TI  - [Is the age of first contact with alcohol of the French really getting younger? A
      recent consensus conference sifts out reality and approximations].

PMID- 22980468
TI  - [Benefits of exercise for people with schizophrenia: a systematic review].
AB  - INTRODUCTION: Previous reviews of exercise and mental health have predominantly
      examined chronic illness and more recently, several psychiatric disorders. There
      is growing evidence that exercise can also be an effective treatment for major
      depressive disorders, anxiety disorders and alcohol dependence. Individuals with
      schizophrenia are more likely to be sedentary than the general population.
      OBJECTIVES: The objectives of this systematic review are to analyse the habits of
      physical activity and examine the literature that has investigated the use of
      exercise as treatment for schizophrenia. METHOD: We systematically reviewed
      psycINFO, Medline/PubMed, SportDiscus, Web of Sciences, and Cochrane Library. The
      searches of databases were conducted from database inception until September
      2010, using a range of search terms to reflect both physical activity and
      schizophrenia. Studies were subsequently considered eligible if they reported on
      quantitative studies investigating the effect of physical activity upon some
      aspect of physical or mental health in individuals with schizophrenia. RESULTS:
      Of the 139 articles retrieved, 19 studies met the inclusion criteria. In
      controlled studies, most authors have underlined the benefits of aerobic
      exercises. These programs may act both on positive symptoms (hallucinations) and
      on negative symptoms. According to certain studies, the positive effect may
      appear in a short time and at the end of the program. No studies assess long-term
      benefits. Small samples of self selected participants, inadequately selected
      control groups are common methodological weaknesses. A recent research has
      directly investigated the potential mechanism underpinning the positive benefits.
      The results indicated that hippocampal volume is plastic in response to aerobic
      exercise. DISCUSSION: We discuss methodological and practical challenges to
      research in this area, and outline several research questions that future work
      should seek to address. Existing studies do suggest that lifestyles, physical
      activity interventions, or regular exercise programmes are possible in this
      population and can have beneficial effects on both the mental and physical health
      and well being of individuals with schizophrenia. CONCLUSION: Research into the
      efficacy and safety of exercise as an intervention in schizophrenia is required
      to support the development of detailed, population-specific guidelines. Larger
      randomised studies are required before any definitive conclusions can be drawn.
      Although studies included in this review are small and used various measures of
      physical and mental health, results indicated that regular exercise programmes
      are possible in this population, and that they can have beneficial effects on
      both physical and mental health. Future research should address issues of
      programme adherence.

PMID- 22980469
TI  - [PerCaDim study: relationship between categorical and dimensional approaches of
      personality].
AB  - PURPOSE: Personality and its disorders have been the subject of many studies in
      philosophy, psychology or medicine. Current nosology gives preference to
      categorical classifications, but a dimensional approach may also be considered.
      Supported by Cloninger's psychobiological model, it refers to concepts of
      temperament (novelty seeking, reward dependence, harm avoidance and persistence)
      and character dimensions (self-directedness, cooperativeness and self
      transcendence). Categorical and dimensional approaches do not appear antinomic,
      and the PerCaDim study tries to verify the hypothesis of correlations existing
      between them. SUBJECTS AND METHODS: One hundred and eleven patients completed two
      personality inventories. The dimensional approach was assessed using the TCI-125
      (short version of the Temperament and Character Inventory) (Cloninger et al.,
      1993 [9]), which includes four dimensions of temperament and three dimensions of
      character. The categorical approach was assessed using Vragenlijst Kenmerken voor
      van de Persoonlijkheid (VKP) (Duijsens et al., 1993 [15,16]), which defines
      personality disorders according to DSM III-R (APA, 1987 [1]). RESULTS: The
      PerCaDim study reveals significant relationships between the dimensions of
      temperament and character and personality disorders. For dimensions of
      temperament: novelty seeking is correlated negatively with schizoid personality
      and positively with antisocial, borderline, histrionic, narcissistic and sadistic
      personalities. Ten out of 13 personalities from DSM III-R are positively
      correlated with harm avoidance. Cluster A and obsessive-compulsive personality
      disorders have negative correlations with reward dependence, whereas five
      pathological personalities have positive correlations with persistence. For
      dimensions of character: all personality disorders are negatively correlated with
      self-directedness. Cooperativeness is negatively correlated with six personality
      disorders. Among the dimensions of character, only self-transcendence has
      positive correlations with personality disorders. DISCUSSION: The PerCaDim study
      highlights various relationships between dimensional and categorical approaches
      of personality. It shows negative correlations between reward dependence and
      cluster A personality disorders, positive correlations between novelty seeking
      and cluster B personality disorders and between harm avoidance and cluster C
      personality disorders. Self-directedness and cooperativeness character's
      dimensions seem to reflect the subject's adaptation, because negative
      correlations were found with all personality disorders. It may be surprising that
      correlations appear positive between self-transcendence dimension and 12
      personality disorders. This result is not striking for "psychotic" personalities,
      but may be questionable for other personalities. CONCLUSION: These results
      confirm previous findings that Cloninger's dimensions can objectify personality
      disorders. Few dimensions of the Temperament and Character Inventory can be
      considered as vulnerability factors. The use of the Temperament and Character
      Inventory will most certainly be of good help in the future to detect or prevent
      a personality disorder in some subjects at risk.

PMID- 22980470
TI  - [Prevalence and risk factors for suicide ideation, plans and attempts in the
      French general population: results from the ESEMeD study].
AB  - BACKGROUND AND OBJECTIVE: Suicide is a public health problem worldwide. The
      objective of this study is to analyse the prevalence and risk factors of suicide
      related outcomes (ideation, plan and attempt) using data from the ESEMeD-France
      project. SUBJECTS AND METHOD: This is a face-to-face household survey carried out
      in a probability representative sample of the adult general population of France.
      A total of 6796 subjects were interviewed using the Composite International
      Diagnostic Interview (CIDI) developed framework of the World Mental Health Survey
      Initiative. Based on evidence that reports of such potentially embarrassing
      behaviour are higher in self-administered than interviewer-administered surveys,
      these questions were printed in a self-administered booklet and referred to by
      letter. RESULTS: Lifetime prevalence of suicide ideation, plan and attempts were
      12.4, 4.4 and 3.4% respectively. Risk of suicide-related outcomes was
      significantly higher among women and younger cohorts. Having a mental disorder
      was associated with an increased risk, especially in the case of psychiatric
      comorbidity. Mental disorders that are associated with an increase in suicidal
      attempts are anxiety disorders (except social phobia), major depressive episodes,
      oppositional defiant disorders, and attention deficit hyperactivity disorders.
      The suicidal risk notably increases in conjunction with multiple mental
      disorders. In this study, employment and marital status do not appear to be a
      risk factor for suicidal behaviour. CONCLUSIONS: The prevalence of suicide
      related outcomes is high when compared with other countries. Results identified
      groups with higher risk (women, young, subjects with a mental disorder and having
      a plan) in which suicide prevention could to be targeted. The results of this
      study suggest that to improve suicide prevention strategies it is necessary to
      perform an in-depth clinical evaluation of suicidal ideas and projects, and
      identify precisely psychiatric comorbidity to allow a more efficient treatment.

PMID- 22980471
TI  - [Reimbursement of opiate substitution drugs to militaries in 2007].
AB  - INTRODUCTION: The use of psychoactive drugs by militaries is not compatible with
      the analytical skills and self-control required by their jobs. Military
      physicians take this problem into consideration by organising systematic drugs
      screening in the French forces. However, for technical reasons, opiates are not
      concerned by this screening with the agreement of the people concerned. The
      estimated number of militaries who use an opiate substitute may be an approach of
      heroin consumption in the French forces. This study describes buprenorphine and
      methadone reimbursements made during 2007 by the national military healthcare
      centre to French militaries. MATERIAL AND METHOD: Each French soldier is
      affiliated to a special health insurance. The national military healthcare centre
      has in its information system, all the data concerning drug reimbursement made to
      French military personnel. This is a retrospective study of buprenorphine and
      methadone reimbursements made during 2007 by the military healthcare centre, to
      militaries from the three sectors of the French forces, and from the gendarmerie
      and joint forces. Only one reimbursement of one of these two drugs during this
      period allowed the patient to be included in our study. Daily drug dose and
      treatment steadiness profile have been calculated according to the criteria of
      the French monitoring centre for drugs and drug addiction. The criteria of the
      National guidelines against frauds have been used to identify misuse of these
      drugs. Doctors' shopping behaviour has also been studied. Finally, the nature of
      the prescriber and the consumption of other drugs in combination with opiate
      substitute have been analysed. RESULTS: One hundred and eighty-one military
      consumers of opiate substitute drugs (167 men and 14 women) participated. This
      sample included people from the three sectors of the French forces as well as
      from the gendarmerie and from the joint forces. The average age of the consumers
      was 26.6 years (20-42 years). The average length of service was 6.1 years
      (maximum 22 years service). One hundred and fifty-nine militaries had been
      delivered buprenorphine, 15 had been delivered methadone and seven had been
      delivered both. The prevalence of opiate substitute drug consumption by the
      militaries (52 per 100,000) is lower than in general population. According to the
      criteria of the National Healthcare Insurance, this population is not affected by
      abuse or fraud behaviour. Doctors' shopping behaviour is unusual. Opiate
      substitutes are prescribed by general physicians in 88% of issues. Only one
      prescriber was a military physician. An analysis of reimbursement of some drugs
      associated with opiate substitute has been made. The sampled military consume
      more psychoactive drugs (anxiolytics, antidepressants, hypnotics) than the French
      population under opiate substitution. CONCLUSION: In our observation, the
      military physician is almost always excluded the process of substitution. His/her
      different responsibilities of care, but also in determining the working aptitude,
      lead to dissimulation behaviour by the militaries. The difficulty for military
      physicians is to identify such consumption. They have to evaluate the capacity to
      work through a physical and psychological examination.

PMID- 22980472
TI  - [Factorial study of the psychopathological factors of morbid obesity in the
      adolescent].
AB  - BACKGROUND: The prevalence of paediatric obesity is high in most countries. Added
      to this, the degree of paediatric obesity is also on the rise. It is however to
      be noted that although the psychological causes of the problem are well known,
      they remain difficult to assess. Facing the great number of adolescents suffering
      from severe obesity, who are looking for treatment and failing to find one, this
      survey aims at facts-finding and analyses of the psychological and
      psychopathological origin and associated severity of obesity, and of the
      parameters that can lead to a successful treatment. METHODS: This survey has been
      carried out among 125 adolescents suffering from grade 2 obesity. To lose weight,
      the adolescents were treated during 1 year at the boarding dietary department of
      the "Institut Medical Pediatrique Clairs-Vallons" in Belgium. The evaluation
      consists in a type CFTMEA-R-2000 psychopathological diagnosis including previous
      traumatic factors, taking into consideration the information regarding weight,
      weight evolution over one year and a quality assessment of the compliance of the
      patient with the treatment. These data have been submitted to the SPADN
      statistical program in order to carry out an analysis taking into account the
      various connections. RESULTS: Our results have underlined that the severity of
      the obesity in our population can be coupled with pathological family environment
      factors such as mental illness, care deficiencies, child abuse and, as a result,
      the presence of a psychopathological diagnosis. The same can be said in cases of
      lesser compliance with the treatment by the patient and his family, although in
      the short term the weight loss is greater. Likewise, a less severe obesity and a
      better compliance with the treatment can be coupled with the absence of both
      psychopathological diagnosis and pathological family environment. CONCLUSION: In
      our sample population, the psychological and psychopathological factors tend to
      be linked with a more severe obesity, and less good compliance with the treatment
      on both individual and family accounts. As a result, obesity could be considered
      as a way for the patient to adapt him/herself or compensate in front of traumatic
      family experiences. The isolation from the family seems therefore indispensable
      for any change in the adolescent, but then raises the problem of long term care
      after hospitalisation. If obesity is an adaptation process, the loss of weight
      could then have deeper psychological implications, implying a more complex follow
      up of the patient.

PMID- 22980473
TI  - [Abnormal electroencephalography results and specific language impairment:
      towards a theoretical neurodevelopmental model?].
AB  - BACKGROUND: Specific language impairment (SLI) is a primary developmental
      disorder in which language is significantly more impaired than other
      developmental domains. Abnormal electroencephalographic recordings without
      clinical seizures are often observed. The aim of this retrospective study was to
      characterize the frequency of these abnormalities, to describe them and to
      analyze their association with anamnestic, clinical, paraclinical and evolution
      characteristics. METHODS: The cases of 35 children with a diagnosis of SLI, who
      also underwent electroencephalography and MRI, were systematically reviewed
      retrospectively. RESULTS: In this population, aged between 4 and 7 years, 49%
      (n=17) of patients exhibited a specific expressive language disorder and 51%
      (n=18) a specific receptive disorder. Forty-nine percent of the children featured
      abnormal electroencephalography results. Abnormalities were essentially localized
      on the left side of the brain and in two specific regions: the temporo-occipital
      (60%) and the frontorolandic (30%) regions. The groups with and without
      abnormalities were compared statistically with each other in terms of clinical,
      paraclinical and evolution characteristics. Evolution data were available for 24
      patients through a telephone interview and for nine patients through a new
      complete language evaluation. The comparison of the two groups showed significant
      differences in terms of severity of the phonological disorder, a higher number of
      delayed acquisition of walking and cleanliness and a higher range of non specific
      psychomotor difficulties. DISCUSSION: A large proportion of children suffering
      from SLI present abnormal electroencephalography recordings with no clinical
      seizures. This rate is much higher than in the general population and the
      abnormalities are essentially localized on the left side of the brain in regions
      known for their specific role in language development. These abnormalities are
      more frequent in children with a severe phonological disorder, suggesting that
      they may share common pathophysiological features with SLI. CONCLUSION: The
      presence of EEG abnormalities in a large group of patients suffering from SLI
      associated with minor neurological abnormalities suggests a possible theoretical
      neurodevelopmental model. Minor neurodevelopmental abnormalities, genetically
      transmitted or acquired during the pre- or perinatal period, may create
      vulnerability towards SLI. This vulnerability, in conjunction with environmental
      influences such as family environment, linguistic stimuli, exposure to multiple
      languages, or transitory hearing loss, might take the form of SLI. This
      hypothesis underlines the importance of prevention and early detection of SLI
      when identifying vulnerable subjects. Monitoring the family early through
      parental guidance and early school support would facilitate the acquisition of
      language.

PMID- 22980474
TI  - [Mild traumatic brain injury and postconcussive syndrome: a re-emergent
      questioning].
AB  - INTRODUCTION: Blast injuries are psychologically and physically devastating.
      Notably, primary blast injury occurs as a direct effect of changes in atmospheric
      pressure caused by a blast wave. The combat-related traumatic brain injuries
      (TBI) resulting from exposure to explosions is highly prevalent among military
      personnel who have served in current wars. Traumatic brain injury is a common
      cause of neurological damage and disability among civilians and servicemen. Most
      patients with TBI suffer a mild traumatic brain injury with transient loss of
      consciousness. A controversial issue in the field of head injury is the outcome
      of concussion. LITERATURE FINDINGS: Most individuals with such injuries are not
      admitted to emergency units and receive a variable degree of medical attention.
      Nevertheless, cranial traumas vary in their mechanisms (blast, fall, road
      accident, bullet-induced craniocerebral injury) and in their gravity (from minor
      to severe). The majority of subjects suffering concussion have been exposed to
      explosion or blast injuries, which have caused minor cranial trauma. Although
      some authors refuse to accept the reality of post-concussion syndrome (PCS) and
      confuse it with masked depression, somatic illnesses or post-traumatic stress, we
      have raised the question again of its existence, without denying the intricate
      links with other psychiatric or neurological disorders. Although the mortality
      rate is negligible, the traumatic sequel after mild traumatic brain injury is
      clear. A difference in initial somatic severity is noted between the serious
      somatic consequences of a severe cranial trauma compared with the apparently
      benign consequences of a minor cranial trauma. However, the long-term
      consequences of the two types of impacts are far from negligible: PCS is a source
      of morbidity. The prognosis for minor cranial traumas is benign at vital level
      but a number of patients will develop long-term complaints, which contrast with
      the negativity of the clinical examination and complementary explorations. The
      origin of these symptoms questions their organic and psychological aetiologies,
      which are potentially associated or intricately linked. After a cerebral
      concussion patients report a cluster of symptoms referred to as postconcussive.
      CLINICAL FINDINGS: Post-concussion syndrome lies within the confines of somatic
      symptoms (headaches, dizziness, and fatigue), cognitive symptoms (memory and
      concentration problems) and affective symptoms (irritability, emotional lability,
      depression, anxiety, trouble sleeping). The nosographical entity of post
      concussion syndrome is still in the process of elaboration following the input of
      new research intended to determine a cluster of specific symptoms. The persistent
      post-concussion syndrome is believed to be due to the psychological effects of
      the injury, biological factors, or a combination of both. Considered in
      isolation, the symptoms of post-concussion syndrome are non-specific and come
      together with other diagnostic frameworks such as characterised depressive
      episodes and post-traumatic stress. Post-concussion syndrome is not specific to
      concussion but can be present in subjects without any previous cranial trauma.
      DISCUSSION: Blast trauma can thus be understood as experiencing a shockwave on
      the brain and as a psycho-traumatic event. The major methodological problem of
      the studies is the quantification of the functional symptoms present in different
      nosographical frameworks, which are often co-morbid. Post-traumatic stress
      disorder is one of several psychiatric disorders that may increase suffering and
      disability among people with mild traumatic brain injury; in addition mood
      disorders also seem to be frequent psychiatric complications among these
      patients. Psychotic disorders after TBI have been associated with several brain
      regions. The establishment of a causative relationship between TBI and
      psychiatric disorders is interesting in terms of our understanding of these
      possible sequelae of TBI. The grey substance of the grey nuclei of the base can
      also be altered by a scissoring mechanism of the perforating arteries. A cortical
      contusion through impression of the cortex on the contours of the cranium is
      frequent. The most common type of injury is traumatic axonal injury. Cerebral
      lesions that are secondary to TBI associate cell deaths through the mechanisms of
      apoptosis and necrosis concerning the nerve and glial cells. The scientific
      objective is to discover an anatomoclinical correlation between the symptoms of
      post-concussion syndrome and objectifiable brain damage. The predictive value of
      serum concentrations of the specific serum markers S-100B and neurone specific
      enolase has been established. CONCLUSION: Cerebral imaging will allow the
      mechanisms concerned in cranial trauma to be better understood and thus may allow
      these mechanisms to be linked with co-morbid post-traumatic psychiatric disorders
      such as depression. The pyschopathological approach provides supplementary
      enlightenment where neuroimaging studies struggle to establish precise
      anatomoclinical correlations between neurotraumatic lesions, state of post
      traumatic stress, and PCS. Moving away from a purely scientific view to focus on
      subjectivity, PCS can establish itself in subjects with no history of head trauma
      thus showing purely psychic suffering. Is the former name of "subjective post
      head injury syndrome" no longer pertinent since the neurobiological affections
      can be objectified? Yet, the latter does not necessarily explain the somatic
      symptoms. Beyond any opposition of a psychic or somatic causality, it shows the
      complexity of this interaction. Admittedly, looking for a neuropathological
      affection is particularly cardinal to propose an aetiological model and objectify
      the lesions, which should be documented using a forensic approach. However,
      within the context of treatment, this theoretical division of the brain and the
      mind becomes less operative: the psychotherapeutic support will on the contrary
      back the indivisibility of the subject, he/she, who faced the "clatter".

PMID- 22980475
TI  - [French adaptation and validation of a scale measuring the fear of childbirth].
AB  - OBJECTIVES: The fear of childbirth, a central aspect of tokophobia, recently
      started to capture the attention of the scientific community as a potential
      determinant of obstetric and post-natal complications. However, studies on this
      subject are still few and this can be partly explained by the lack of validated
      instruments, especially in French. This paper presents the results from two
      studies designed to develop and evaluate the psychometric properties of a French
      version of the Traumatic Event Scale (TES), adapted to assess fear of childbirth
      (Soderquist et al., 2004 [21]). METHOD: The first study presents details
      regarding the development of this scale and checks the quality of the resulting
      items as well as their internal consistency, convergent validity and factorial
      validity. This study relied on a sample of 65 mothers with at least one child
      under the age of 36 months. In the second study, the psychometric properties of
      the instrument developed in Study 1 were tested more systematically on a sample
      of 204 women who were at the time experiencing their first pregnancy. RESULTS AND
      CONCLUSION: The results from the first study show adequate psychometric
      properties, strong correlations with measurements assessing worry, and support a
      five factor model. Results from this second study replicated the results from the
      first one on the basis of confirmatory factor analyses. Findings presented in
      these studies confirm that this instrument presents very good psychometric
      properties as a measurement of the fear of childbirth in pregnant women.

PMID- 22980476
TI  - [Efficacy of a cognitive-behavioral group therapy in patients with fear of
      blushing].
AB  - INTRODUCTION: Cognitive behavioral therapy (CBT) has shown to be effective in the
      treatment of social anxiety disorders (SAD). However, fear of social blushing is
      almost never measured as a therapeutic outcome variable, even though some data
      suggest that this dimension constitutes a specific syndrome in social anxiety
      spectrum, justifying specific therapeutic strategies. For these reasons, we
      developed a group therapy program including a combination of task concentration
      training (TCT) and other CBT strategies targeting fear of blushing. AIM: We aimed
      to investigate the efficacy of this program in an open trial conducted in 55
      patients suffering from SAD (Diagnostic and statistical manual of mental
      disorders IV criteria) with fear of blushing. METHOD: Throughout a program
      including eleven weekly sessions, systematic measurements of fear of blushing and
      other anxiety and personality dimensions were performed at inclusion, at the end
      of the therapy and 3 months later, in order to explore the therapeutic effects of
      the program on fear of blushing, social anxiety, and other dimensions (Liebowitz
      social anxiety scale, blushing propensity questionnaire, Rathus assertiveness
      scale, Rosenberg self-esteem scale, Hospital anxiety and depression scale,
      Sheehan disability scale). The statistical analyses compared the scores of all
      measurements at inclusion, at the end of the therapy, and 6 months later. We also
      calculated the effect size obtained after treatment, and performed a logistic
      regression to determine the factors associated with a remission of fear of
      blushing after therapy. RESULTS: The main outcome criterion - the Salpetriere
      fear of blushing questionnaire (SFBQ) score - was significantly reduced after
      treatment (P<0.001) and remained stable at follow up. A satisfying effect size
      was obtained on this score after treatment (1.7), and 57.6% of subjects were
      considered in remission on the basis of a SFBQ score of 6 or less. Other
      measurements of blushing propensity, social anxiety, assertiveness, self-esteem,
      anxiety, depression and disability showed significant improvement after treatment
      and reductions remained stable at 3-month follow-up. To be a female and to have a
      low SFBQ score at inclusion appeared as two independent predictors of good
      improvement. DISCUSSION: Despite the preliminary nature of this study, our
      results suggest the efficacy of this specific group therapy program for
      erythrophobia. Further controlled and comparative trials are now required to
      confirm the program efficacy including a comparison between group and individual
      therapies.

PMID- 22980477
TI  - [Dysphagia or dysphagias during neuroleptic medication?].
AB  - INTRODUCTION: Dysphagia is a common symptom in the general population, and even
      more among psychiatric patients, but rarely seen as a sign of seriousness. It is
      a cause of death by suffocation, and more or less serious complications, and
      therefore should be diagnosed and treated. Among psychiatric patients, organic
      and iatrogenic aetiologies, as well as risk factors are identified, which worsen
      this symptom when associated. It is now accepted that neuroleptics can aggravate
      or cause dysphagia. They act by several pathophysiological ways on the different
      components of swallowing, which can be identified by dynamic tests in the upper
      aerodigestive tract endoscopy. LITERATURE FINDINGS: This symptom is rarely
      reported by patients and often underestimated by caregivers. The frequency of
      swallowing disorders is not known. Dysphagia is a cause of complications and an
      increase in mortality rates among psychiatric patients. It has also been found
      that the average number of psychotropic drugs in patients who die by cafe
      coronary is significantly higher than in other patients. There are several phases
      in swallowing: oral, pharyngeal, and oesophageal. Swallowing disorders can affect
      each of these phases, or several at once: (a) Extrapyramidal syndrome: dysphagia
      is present in drug induced Parkinson's syndromes, but prevalence is not known. It
      is most often associated with another symptom of the extrapyramidal syndrome, but
      can also be isolated, making its diagnosis more difficult. Dysphagia is due to a
      slowing down in the oral and pharyngeal reflex, called bradykinesia; (b) Tardive
      dyskinesia: the oro-pharyngo-oesophageal dyskinesia is the most common type.
      Oesophageal dyskinesia causes asynchronous and random movements of the
      oesophagus, resulting in dysphagia. It appears mostly beyond 3 months of
      treatment with neuroleptics; (c) Acute laryngeal or oesophageal dystonia,
      associated or not with orofacial dystonia, is characterised by an impairment in
      the oesophageal muscle contraction and a hypertonia of the upper sphincter of the
      oesophagus; (d) Polyphagia or "binge eating", is frequent in psychotic patients;
      (e) Finally, there are risk factors for dysphagia: xerostomia, poor dental
      status, advanced age, neurological diseases, polypharmacy, sedative drugs, CNS
      depression, etc., which worsen the symptom. CASE REPORT: Mr J., aged 28, with no
      psychiatric history, is admitted to the Unit for Difficult Patients in Villejuif
      for behavioural disorder with homicide on the street. The patient was restrained
      by passers-by and suffers a head injury and a fracture of the transverse process
      of L1 vertebra. A cranial CT scan is performed in the emergency room, it is
      normal. The patient is not known to psychiatric services, and has never taken
      neuroleptics. Mr J. is homeless, known in his neighbourhood for "his noisy
      delirium on the street and repeated alcohol abuse." After being arrested by the
      police in this context, a first psychiatric examination is conducted. The medical
      certificate states that his condition is not compatible with custody. Mr J.
      remains mute; he has stereotyped gestures and strange attitudes. No delusion is
      verbalized. He receives vials of loxapine 50mg causing sedation. At his arrival
      in the department, Mr J. has the same clinical picture, with a rigid and
      inexpressive face, reluctance, major unconformity, poor speech. The search for
      drugs in urine is positive for cannabis. The diagnosis of schizophrenia is
      rapidly raised, motivating further prescription of loxapine 300 mg daily in
      combination with clonazepam 6 mg daily. From the earliest days, dysphagia to
      solids with choking and regurgitation is noted, aggravated by the increase of
      loxapine treatment of 450 mg / day to 700 mg / day, 7 days after admission. A
      physical examination is performed before the worsening of dysphagia, it is
      normal, and in particular, reveals no extrapyramidal syndrome. An anti
      cholinergic corrector is introduced, without clinical improvement. A new physical
      examination is performed; it is normal except for sedation and a slight deviation
      of the uvula. Upper gastrointestinal endoscopy shows no anatomical lesion. No
      functional assessment of swallowing is done however. At this stage, the suspicion
      of neuroleptic induced dysphagia appears to be the most likely hypothesis.
      Treatment with loxapine is then stopped, resulting in a very rapid clinical
      improvement. Aripiprazole 15 mg / d is introduced. Dysphagia does not reoccur.
      DISCUSSION: Loxapine is an atypical antipsychotic, with a lower risk of
      neurological side effects than first generation of antipsychotics. These side
      effects are however numerous and from diverse pathophysiological mechanisms.
      Loxapine is an antagonist of dopamine and serotonin which is involved in the
      regulation of several neurotransmitters, explaining the multiple mechanisms
      involved in the onset of dysphagia: first, blocking dopamine D2 receptors in the
      striatum, causing motor side-effects of central origin, in addition to peripheral
      effects of the molecule, which impairs swallowing. In principle, the antagonist
      activity on serotonin 5-HT2A receptors increases dopaminergic activity in the
      striatum, reducing the risk of extrapyramidal symptoms and tardive dyskinesia,
      without avoiding them completely. In addition to these mechanisms, cholinergic
      blockade reduces oesophageal mobility and pharyngeal reflex. Moreover, the
      antihistamine, anti-cholinergic and adrenergic receptor blocking alpha-1 can
      cause sedation, which aggravates the symptom. Finally, the depression of the
      bulbar centres reduces the swallowing reflex and gag reflex altering the intake
      of food. CONCLUSIONS: The swallowing disorder caused by neuroleptics may occur
      regardless of the molecule or drug class to which it belongs. It can be found
      even in the absence of any other neurological signs. It is important to search
      for the aetiological diagnosis for treatment. At the crossroads of several
      specialties, swallowing disorders are difficult to diagnose and treat. They are
      frequently underestimated, partly because patients rarely complain. In our case
      report, the diagnosis was ascertained by the removal of the medication, without
      functional evidence, probably by a lack of collaboration between the physician
      and the endoscopist who had not performed any dynamic investigation of
      swallowing. This case illustrates the importance of knowing the different
      mechanisms underlying dysphagia in psychiatric patients, and good communication
      with gastroenterologists to establish a precise diagnosis of the disorder, and
      adapt the therapy.

PMID- 22980478
TI  - [Chronic subdural hematoma and psychotic decompensation].
AB  - BACKGROUND: In Tunisia, with the remarkable progress in health, life expectancy
      has significantly increased these last decades. Indeed, in 2004, 9.3% of the
      population was aged over 60, and this rate is predicted to reach 17% in 2029 and
      about 29% by 2050. In the elderly, chronic subdural hematoma (HSDC) may be caused
      by even minimal trauma or occur spontaneously. The manifestations of this type of
      accumulation depend on the degree of cerebral compression and the localisation of
      the mass. They could be delirium, dementia, convulsions or psychiatric disorders
      (frontal location). CASE REPORT: When the psychiatric presentation predominates,
      the decision to hospitalise an elderly person in a psychiatric unit is difficult
      and often avoided. We report the case of an 81 year-old man without history of
      medical condition or personal or family psychiatric history, who, in 2000, began
      to exhibit behavioural disorders, delusions of persecution and jealousy, visual
      hallucinations and sexual disinhibition. This clinical picture that set in so
      insidiously and in moderate intensity was long tolerated by the family circle.
      The patient was admitted to a psychiatric hospital in January 2008 with the
      worsening of the symptoms. The clinical examination and investigations confirmed
      the diagnosis of chronic frontoparietal subdural hematoma without compression.
      The decision in neurosurgery was to refrain from surgical drainage and administer
      high doses of steroids under supervision (clinical and biological). The evolution
      was good with progressive resorption of the hematoma to complete recovery.
      Currently, the patient is symptom free and the last CT scan on 03/11/2010
      confirms the total resorption of the hematoma. CONCLUSION: It appears from this
      case and review of the literature that various psychiatric manifestations may
      reveal an HSDC and that, in the elderly, neuroimaging should be systematic, even
      for minor symptoms. The total resorption led to the disappearance of psychiatric
      symptoms in most patients, but this remains a topic of discussion for patients
      who retain residual symptoms, even after resorption of the mass. Caution is
      required when faced with an elderly person suffering, and we should strive to
      explore all possible causes before jumping to the conclusion of the fatality of
      growing old.

PMID- 22980479
TI  - [Repetitive transcranial magnetic stimulation in major depression: response
      factor].
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a brain
      stimulation technique that has been investigated as a novel treatment for
      psychiatric disorders, notably in major depression, and has shown statistically
      significant effects. The authors found it necessary to propose an up-to-date
      review of positive predictors for antidepressive response to repetitive
      transcranial magnetic stimulation. METHOD: Based on an exhaustive consultation of
      Medline data, supplemented by a manual research, only works evaluating response
      factors of rTMS in major depression were retained. RESULTS: Twenty-nine studies
      were retained, including meta-analyses, reviews, randomized controlled trials and
      open trials. The most concordant data clearly indicate that a high score of
      treatment resistance, a long duration of current episode, advanced age, and
      psychotic symptoms are negative predictors for treatment response to rTMS. In the
      older patients, menopausal women are especially concerned. However, some
      parameters should be adapted to the degree of cortical atrophy such as intensity
      of stimulation or total number of rTMS sessions. Previous response to rTMS
      therapy seems to be a good predictor contrary to non-response to
      electroconvulsive therapy. Adjunctive antidepressant treatment shows greater
      responsiveness to rTMS contrary to benzodiazepine or anticonvulsant treatment. To
      our knowledge, no study compares unipolar and bipolar depression, the profile of
      depression is not established yet. Imaging studies show that TMS antidepressant
      responders differed from non-responders in inferior frontal activity, at
      baseline, and even more so following treatment. Furthermore, reduced baseline
      cerebral metabolism in cerebellar, temporal, anterior cingulate and occipital
      regions of the brain was correlated with improvement after two weeks of fast
      (20Hz) left dorsolateral prefrontal cortex (DLPFC) rTMS. Additionally, a right
      frontal region emerges with divergent polarity in the metabolic prediction of
      response to low rTMS. Inhibiting right DLPFC or stimulating DLPFC shows similar
      results, the choice on the side of stimulation does not seem determining.
      Bilateral stimulation for the moment does not seem superior to unilateral
      stimulation. Parameters of stimulation associated with effectiveness of rTMS are
      an intensity of stimulation higher than 100% of the motor threshold, a number of
      stimulations per sessions superior to 1000, and a full number of days of
      treatment greater than 10. DISCUSSION: Parameters of stimulation must be adapted
      according to the treated patients. For example, older patients who present
      cortical atrophy need higher intensity of stimulation. Other criteria could
      influence effectiveness of rTMS in the same way. Would it be necessary, for
      example, to adapt the duration or the intensity of stimulation according to the
      severity of the depressive episode or its duration of evolution? Do antecedents
      of resistance to a pharmacological treatment oblige us to stimulate differently?
      Few studies exceed 10 days of treatment; will longer duration of treatment be
      more effective? Also, we did not find any data on the interest of maintenance
      treatment among responders. Should the characteristics of the depressive disorder
      or its evolution require maintenance treatment? What will be its rhythm and its
      duration? Should we adapt rTMS parameters to abnormalities highlighted by
      functional neuroimagery? The prospects for work remain numerous.

PMID- 22980480
TI  - CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis.
AB  - Relationships between concentrations of cerebrospinal fluid (CSF) kynurenic acid
      (KYNA) and suicidal behavior were evaluated in 59 patients with psychosis after
      22 years of follow-up. Three patients died from suicide and nine patients had a
      history of attempted suicide. Patients with attempted suicide had significantly
      lower concentrations of CSF KYNA.

PMID- 22980481
TI  - Sensation-seeking, social anhedonia, and impulsivity in substance use disorder
      patients with and without schizophrenia and in non-abusing schizophrenia
      patients.
AB  - Substance use disorders (SUDs) are common in patients with schizophrenia and this
      comorbidity is associated with a poorer prognosis, relative to non-abusing
      patients. One hypothesis that has been advanced in the literature is that dual
      diagnosis (DD) patients may have a different personality profile than non-abusing
      schizophrenia patients. The present case-control study aimed to characterize
      levels of personality traits (sensation-seeking, social anhedonia, and
      impulsivity) in substance abuse/dependence patients with (DD group; n=31) and
      without schizophrenia (SUD group; n=39), relative to non-abusing schizophrenia
      patients (SCZ group; n=23), and healthy controls (n=25). Impulsivity was assessed
      using the Barratt Impulsivity Scale. Sensation-seeking was assessed using the
      Zuckerman Sensation Seeking Scale. Social anhedonia was assessed with the Chapman
      Social Anhedonia Scale. We found that sensation-seeking was significantly higher
      in DD and SUD, relative to SCZ patients. We found that social anhedonia was
      significantly elevated in DD and SCZ, relative to healthy controls. We found that
      impulsivity was significantly higher in DD, SCZ and SUD patients, compared to
      healthy controls. The results suggest that sensation-seeking is prominent in
      substance abuse/dependence (irrespective of schizophrenia), social anhedonia is
      prominent in schizophrenia (irrespective of substance abuse/dependence), and
      impulsivity is prominent in all three populations.

PMID- 22980483
TI  - Development and evidence base of a new efficient assessment instrument for
      international use by nurses in community settings with older people.
AB  - In a world where 12% of the population, and 22% of that of more developed
      regions, will be older than 65 years by 2030, new targeted programs and social
      protections will be needed for older people in many countries. As economic and
      human resources become more scarce, efficient instruments are needed to realize
      sustainable health care for these large populations of older subjects. To address
      this need a new assessment instrument was developed. The core of the instrument
      consists of focused geriatric assessment by a health or social care practitioner
      working in primary or community care, most often a nurse. The assessment data
      result in an efficiently targeted care and welfare action plan based on the
      patients' priorities. This instrument was initially developed, tested and spread
      within Europe, and then in validation studies across all WHO regions of the
      world. Because of the urgent societal questions on quality and sustainability of
      primary health care, especially for older people, we briefly review and summarize
      the development and evidence base of the instrument, which was called EASY-Care
      Standard. In a series of studies across many populations it proved to have high
      acceptability, reliability, validity and cost-effectiveness. Therefore, EASY-Care
      has great potential as a universal tool for global use in promoting independence
      in old age, and can make an important contribution to the quality and
      sustainability of health and social care in our aging societies.

PMID- 22980484
TI  - Social capital in pregnancy and postpartum depressive symptoms: a prospective
      mother-child cohort study (the Rhea study).
AB  - BACKGROUND: Depression, and to a lesser extent postpartum depressive symptoms,
      have been associated with characteristics of the social environment and social
      capital. Up to the present, mostly cross-sectional studies have explored such an
      association without providing a clear temporal relationship between social
      capital and depression. OBJECTIVES: To estimate prospectively the effect of
      individual-level self-reported maternal social capital during pregnancy on
      postpartum depressive symptoms. DESIGN: Prospective mother-child cohort (Rhea
      study). SETTINGS: 4 prenatal clinics in Heraklion, Crete, Greece. PARTICIPANTS:
      All women for one year beginning in February 2007. From the 1388 participants,
      complete data were available for 356 women. METHODS: Women self-completed two
      questionnaires: The Social Capital Questionnaire at about the 24th week of
      gestation and the Edinburgh Postnatal Depression Scale (range 0-30) at about the
      8-10th week postpartum. Maternal social capital scores were categorized into
      three groups: the upper 10% was the high social capital group, the middle 80% was
      the medium and the lowest 10% was the low social capital group that served as the
      reference category. Multivariable log-binomial and linear regression models were
      performed for: the whole available sample; for participants with a history of
      depression and/or prenatal EPDS>=13; for participants without any previous or
      current depression and prenatal EPDS score<13. Potential confounders included
      demographic, socio-economic, lifestyle and pregnancy characteristics that have an
      established or potential association with maternal social capital in pregnancy or
      postpartum depressive symptoms or both. RESULTS: Higher maternal social capital
      was associated with lower EPDS scores (highest vs lowest group: beta-coefficient=
      3.95, 95% CI -7.75, -0.14). Similar effects were noted for the subscale value of
      life/social agency (highest vs lowest group: beta-coefficient=-5.96, 95% CI 
      9.52, -2.37). This association remained significant for women with and without
      past and/or present depression only for the subscale value of life/social agency
      although with a more imprecise estimate. No effect was found for participation, a
      structural dimension of social capital. CONCLUSIONS: Women with higher individual
      level social capital in mid-pregnancy reported less depressive symptoms 6-8 weeks
      postpartum. Given the proposed association of perceptions of the social
      environment with postpartum depressive symptoms, health professionals should
      consider evidence-based interventions to address depression in a social
      framework.

PMID- 22980485
TI  - Effect of therapeutic hypothermia according to severity of sepsis in a septic rat
      model.
AB  - AIM OF STUDY: The effects of therapeutic hypothermia (HT) during experimental
      sepsis may be influenced by disease severity. We experimentally investigated the
      effect of therapeutic HT on varying disease severity in a septic rat model.
      MATERIALS AND METHODS: An adult male Sprague-Dawley rat model of intra-abdominal
      sepsis was used. To modify the disease severity, we used two different models; a
      moderate severe sepsis model (MSSM) and a severe septic shock model (SSSM). All
      rats were randomized to a hypothermia group (HT, 30-32 degrees C) or a
      normothermia group (NT, 36-38 degrees C) 1h after sepsis induction in each model.
      HT was maintained for 4h and rewarming was conducted for 2h. Survival time was
      recorded for up to 12h in the SSSM group and 24h in the MSSM group. Acute lung
      and liver injury, cytokine, and malondialdehyde (MDA) levels were investigated 7h
      after sepsis induction. Hemodynamic profiles were also evaluated. RESULTS: In the
      SSSM, there were survival benefits and reduced acute lung and liver injury with
      therapeutic HT. Therapeutic HT was also associated with significantly reduced
      levels of plasma interleukin-6 and tissue malondialdehyde (MDA) levels in the
      liver and lung compared with the NT group in the SSSM. There was a tendency for
      the mean arterial pressure to be higher in the HT group compared to the NT group
      in the SSSM. In MSSM, however, there was no such beneficial effect. CONCLUSION:
      In this rat model of severe septic shock, therapeutic HT showed beneficial
      effects. In contrast, therapeutic HT did not show protective effect in the
      moderate sepsis model.

PMID- 22980486
TI  - Molecular characterization and immunological roles of avian IL-22 and its soluble
      receptor IL-22 binding protein.
AB  - As a member of the interleukin (IL)-10 family, IL-22 is an important mediator in
      modulating tissue responses during inflammation. Through activation of STAT3
      signaling cascades, IL-22 induces proliferative and anti-apoptotic pathways, as
      well as antimicrobial peptides (AMPs), that help prevent tissue damage and aid in
      its repair. This study reports the cloning and expression of recombinant chicken
      IL-22 (rChIL-22) and its soluble receptor, rChIL22BP, and characterization of
      biological effects of rChIL-22 during inflammatory responses. Similar to
      observations with mammalian IL-22, purified rChIL-22 had no effect on either
      peripheral blood mononuclear cells (PBMCs) or lymphocytes. This was due to the
      low expression of the receptor ChIL22RA1 chain compared to ChIL10RB chain. rChIL
      22 alone did not affect chicken embryo kidney cells (CEKCs); however, co
      stimulation of CEKCs with LPS and rChIL-22 enhanced the production of pro
      inflammatory cytokines, chemokines and AMPs. Furthermore, rChIL-22 alone
      stimulated and induced acute phase reactants in chicken embryo liver cells
      (CELCs). These effects of rChIL-22 were abolished by pre-incubation of rChIL-22
      with rChIL22BP. Together, this study indicates an important role of ChIL-22 on
      epithelial cells and hepatocytes during inflammation.

PMID- 22980487
TI  - The cardiocerebral resuscitation protocol for treatment of out-of-hospital
      primary cardiac arrest.
AB  - Out-of-hospital cardiac arrest (OHCA) is a significant public health problem in
      most westernized industrialized nations. In spite of national and international
      guidelines for cardiopulmonary resuscitation and emergency cardiac care, the
      overall survival of patients with OHCA was essentially unchanged for 30 years-
      from 1978 to 2008 at 7.6%. Perhaps a better indicator of Emergency Medical System
      (EMS) effectiveness in treating patients with OHCA is to focus on the subgroup
      that has a reasonable chance of survival, e.g., patients found to be in
      ventricular fibrillation (VF). But even in this subgroup, the average survival
      rate was 17.7% in the United States, unchanged between 1980 and 2003, and 21% in
      Europe, unchanged between 1980 and 2004. Prior to 2003, the survival of patients
      with OHCA, in VF in Tucson, Arizona was less than 9% in spite of incorporating
      previous guideline recommendations. An alternative (non-guidelines) approach to
      the therapy of patients with OHCA and a shockable rhythm, called Cardiocerebral
      Resuscitation, based on our extensive physiologic laboratory studies, was
      introduced in Tucson in 2003, in rural Wisconsin in 2004, and in selected EMS
      areas in the metropolitan Phoenix area in 2005. Survival of patients with OHCA
      due to VF treated with Cardiocerebral Resuscitation in rural Wisconsin increased
      to 38% and in 60 EMS systems in Arizona to 39%. In 2004, we began a statewide
      program to advocate chest compression-only CPR for bystanders of witnessed
      primary OHCA. Over the next five years, we found that survival of patients with a
      shockable rhythm was 17.7% in those treated with standard bystander CPR (mouth-to
      mouth ventilations plus chest compression) compared to 33.7% for those who
      received bystander chest-compression-only CPR. This article on Cardiocerebral
      Resuscitation, by invitation following a presentation at the 2011 Danish Society
      Emergency Medical Conference, summarizes the results of therapy of patients with
      primary OHCA treated with Cardiocerebral Resuscitation, with requested emphasis
      on the EMS protocol.

PMID- 22980488
TI  - Grip strength is a predictor of bone mineral density among adolescent combat
      sport athletes.
AB  - The aim of this study was firstly to investigate the correlation between bone
      parameters and grip strength (GS) in hands, explosive legs power (ELP), and
      hormonal parameters; second, to identify the most determinant variables of bone
      mineral density (BMD) among adolescent combat sport athletes. Fifty combat sport
      athletes aged 17.1 +/- 0.2 year were compared with 30 sedentary subjects matched
      for age, height, and pubertal stage. For all subjects, the BMD in deferent sites
      associated with anthropometric parameters were measured by dual-energy X-ray
      absorptiometry. The growth hormone (GH) and testosterone (TESTO) concentrations
      were tested. The GS in dominant (GSDA) and nondominant arms (GSNDA) and ELP were
      evaluated. All BMD measured were greater in athletes than in sedentary group
      (p<0.01). The GS and ELP showed higher values in athletes than in sedentary group
      (p<0.01). The BMD in all sites were correlated with weight, but without
      correlation with height. The GSNDA and ELP were significantly correlated with BMD
      of both spine and legs. The GH was correlated with the BMD of whole body and
      spine (p<0.05). The TESTO was only correlated with BMD of the arms (p<0.01). The
      best predictor of BMD measurements is GSNDA. This study has proved the osteogenic
      effect of combat sports practice, especially judo and karate kyokushinkai.
      Therefore, children and adolescent should be encouraged to participate in combat
      sport. Moreover, it suggested that the best model predicting BMD in different
      sites among adolescent combat sports athletes was the GSNDA.

PMID- 22980489
TI  - Cortical bone thickness and bone mineral density.

PMID- 22980490
TI  - Study of bone mass in young daughters of women with fracture of the distal end of
      the radius.
AB  - The main aim was to assess whether young and healthy daughters of women with
      fractures of the distal end of the radius (DER) had less bone mass than the
      control group. In an observational study of cases and controls (1:1), the
      daughters of women with fractures of DER (96) were selected at the age of
      reaching the peak of bone mass and compared with a control group (91). All women
      underwent medical history, analytical determinations, and densitometry. In the
      case group, we found lower bone mass values at the spine and femoral neck than
      the control group. We also found a lower bone mass at the hips of daughters of
      women with 1 or more osteoporotic fractures associated with DER and at the lumbar
      spine in those whose mothers had densitometric osteoporosis. In conclusion, young
      daughters of women with fractures of DER had lower levels of bone mass density,
      with a possible "location-specific" occurrence based on the presence of 1 or more
      osteoporotic fractures associated with DER or on the presence of maternal
      densitometric osteoporosis.

PMID- 22980491
TI  - Temporal effects of infection control practices and the use of antibiotics on the
      incidence of MRSA.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) has spread
      throughout the world and has become highly endemic worldwide. The need for
      implementing MRSA control strategies is no longer a matter of debate. AIM: To
      determine the temporal association between various infection control practices,
      the use of antibiotics and the incidence of MRSA in a 1200-bed French university
      hospital. METHODS: A multi-variate time-series analysis, based on monthly data
      from a nine-year period (January 2000-December 2008), was performed in a 1200-bed
      French university hospital to determine the temporal association between
      different variables and the incidence of MRSA. MRSA colonization pressure,
      infection control practices and use of antibiotics were considered in the
      analysis. FINDINGS: Time-series analysis showed a positive significant
      relationship between the incidence of hospital-acquired MRSA (HA-MRSA) and MRSA
      colonization pressure, the use of antibiotics (fluoroquinolones, macrolides and
      aminoglycosides) and the use of gloves. Conversely, a global negative correlation
      was observed between the incidence of HA-MRSA and the use of alcohol-based hand
      rub. Overall, the model explained 40.5% of the variance in the monthly incidence
      of MRSA. CONCLUSION: This study showed that admission of patients with MRSA, the
      use of antibiotics and infection control practices contributed to the incidence
      of HA-MRSA. This suggests that efforts should be focused on high compliance with
      hand disinfection. These results also raise concerns about the use of gloves when
      caring for patients with MRSA.

PMID- 22980492
TI  - Antitumor effectiveness of electrochemotherapy: a systematic review and meta
      analysis.
AB  - BACKGROUND: This systematic review has two purposes: to consolidate the current
      knowledge about clinical effectiveness of electrochemotherapy, a highly effective
      local therapy for cutaneous and subcutaneous tumors; and to investigate the
      differences in effectiveness of electrochemotherapy with respect to tumor type,
      chemotherapeutic drug, and route of drug administration. METHODS: All necessary
      steps for a systematic review were applied: formulation of research question,
      systematic search of literature, study selection and data extraction using
      independent screening process, assessment of risk of bias, and statistical data
      analysis using two-sided common statistical methods and meta-analysis. Studies
      were eligible for the review if they provided data about effectiveness of single
      session electrochemotherapy of cutaneous or subcutaneous tumors in various
      treatment conditions. RESULTS: In total, 44 studies involving 1894 tumors were
      included in the review. Data analysis confirmed that electrochemotherapy had
      significantly (p < .001) higher effectiveness (by more than 50%) than bleomycin
      or cisplatin alone. The effectiveness was significantly higher for intratumoral
      than for intravenous administration of bleomycin (p < .001 for CR%, p = .028 for
      OR%). Bleomycin and cisplatin administered intratumorally resulted in equal
      effectiveness of electrochemotherapy. Electrochemotherapy was more effective in
      sarcoma than in melanoma or carcinoma tumors. CONCLUSIONS: The results of this
      review shed new light on effectiveness of electrochemotherapy and can be used for
      prediction of tumor response to electrochemotherapy with respect to various
      treatment conditions and should be taken into account for further refinement of
      electrochemotherapy protocols.

PMID- 22980495
TI  - Alteration of the gene expression profile of T-cell receptor alphabeta-modified T
      cells with diffuse large B-cell lymphoma specificity.
AB  - Antigen-specific, T-cell receptor (TCR)-modified cytotoxic T lymphocytes (CTLs)
      that target tumors are an attractive strategy for specific adoptive
      immunotherapy. Little is known about whether there are any alterations in the
      gene expression profile after TCR gene transduction in T cells. We constructed
      TCR gene-redirected CTLs with specificity for diffuse large B-cell lymphoma
      (DLBCL)-associated antigens to elucidate the gene expression profiles of TCR gene
      redirected T-cells, and we further analyzed the gene expression profile pattern
      of these redirected T-cells by Affymetrix microarrays. The resulting data were
      analyzed using Bioconductor software, a two-fold cut-off expression change was
      applied together with anti-correlation of the profile ratios to render the
      microarray analysis set. The fold change of all genes was calculated by comparing
      the three TCR gene-modified T-cells and a negative control counterpart. The gene
      pathways were analyzed using Bioconductor and Kyoto Encyclopedia of Genes and
      Genomes. Identical genes whose fold change was greater than or equal to 2.0 in
      all three TCR gene-redirected T-cell groups in comparison with the negative
      control were identified as the differentially expressed genes. The differentially
      expressed genes were comprised of 33 up-regulated genes and 1 down-regulated gene
      including JUNB, FOS, TNF, INF-gamma, DUSP2, IL-1B, CXCL1, CXCL2, CXCL9, CCL2,
      CCL4, and CCL8. These genes are mainly involved in the TCR signaling, mitogen
      activated protein kinase signaling, and cytokine-cytokine receptor interaction
      pathways. In conclusion, we characterized the gene expression profile of DLBCL
      specific TCR gene-redirected T-cells. The changes corresponded to an up
      regulation in the differentiation and proliferation of the T-cells. These data
      may help to explain some of the characteristics of the redirected T-cells.

PMID- 22980497
TI  - European drug reimbursement systems' legitimacy: five-country comparison and
      policy tool.
AB  - OBJECTIVES. In a democratic system, decision makers are accountable for the
      reasonableness of their decisions. This presumes (i) transparency, (ii) relevance
      of the decision criteria, (iii) revisability of decisions, and (iv)
      enforcement/regulation. We aim to (i) evaluate the extent to which drug
      reimbursement decision-making processes in different contexts meet these
      conditions and (ii) develop, starting from these findings, a framework for
      improving the transparency and the relevance of used decision criteria. METHODS.
      We evaluated the Austrian, Belgian, French, Dutch, and Swedish drug reimbursement
      systems. Based on this evaluation, we developed a framework for improving the
      transparency of drug reimbursement decision-making processes. It makes explicit
      the questions often addressed implicitly during decision-making processes as well
      as criteria for answering each question. RESULTS. Transparency of appraisal
      processes varies across systems. Justification with explicit criteria is
      generally limited. Although relevant criteria are similar across systems, their
      operationalization varies and their role in the appraisal process is not always
      clear. All systems seem to implicitly address five key questions, relating to (i)
      the medical, therapeutic, and societal need for treatment; (ii) preparedness to
      pay for treating the condition as a principle and (iii) for using the treatment
      under consideration; (iv) preparedness to pay more compared with alternatives;
      and (v) actual willingness to pay from public resources. CONCLUSIONS.
      Transparency of the appraisal process can be improved by using an explicit
      decision framework. Systematic use of such a framework enhances consistency
      across decisions, allows justification of value judgments, and thus enhances
      legitimacy of societal decision making.

PMID- 22980498
TI  - Allergic contact dermatitis: xenoinflammation of the skin.
AB  - Many xenobiotic chemicals cause sterile inflammation. This xenoinflammation is
      often induced by protein reactive contact allergens resulting in allergic contact
      dermatitis (ACD). Recent findings reveal that these chemicals mimick infection by
      triggering innate immune responses via pattern recognition receptors (PRRs) and
      endogenous danger signals. The emerging cellular responses in ACD are mediated by
      various innate effector cells. Here, an important role for mast cells has now
      been recognized. Eventually, chemical specific T cells such as CD8+ and CD4+
      Tc1/Th1 as well as Tc17/Th17 cells are activated. Langerhans cells may serve a
      tolerogenic function. The mechanisms of tolerance induction by ultraviolet
      irradiation or by very low doses of contact allergen are now understood in much
      greater detail.

PMID- 22980499
TI  - Embryo genomics: Embryo Genomics meeting, Bonn, September 2011.

PMID- 22980500
TI  - Expression and regulation of 12/15-lipoxygenases in human primary macrophages.
AB  - OBJECTIVES: Atherosclerosis is a chronic disease characterized by two main
      features, lipid retention and inflammation. The 12/15-lipoxygenases play a two
      faced role in atherosclerosis with pro-inflammatory effects through oxidation of
      LDL and anti-inflammatory effects through lipid mediator synthesis. In cells
      involved in atherosclerosis the 12-lipoxygenase ALOX12 and the two 15
      lipoxygenases, ALOX15 and ALOX15B may be expressed but their expression has not
      yet been investigated in detail. METHODS: To investigate the regulation of
      ALOX12, ALOX15 and ALOX15B in human macrophages we measured basal mRNA and
      protein expression during differentiation of monocytes to macrophages and
      stimulated expression in macrophages. RESULTS: The results show an increase of
      ALOX15B during the differentiation of monocytes to macrophages, while the
      expression of ALOX12 and ALOX15 remains on the same low level. Stimulation of
      macrophages with a set of cytokines and with hypoxia revealed that IL-4, IL-13,
      LPS and hypoxia further increase the ALOX15B mRNA. Western blot analysis showed
      that IL-4, LPS and hypoxia increase the ALOX15B protein expression, whereas IL-13
      has no effect on the protein levels. IL-4 and IL-13 also enhance ALOX15 mRNA and
      protein expression, whereas none of the stimuli has an impact on ALOX12
      expression. CONCLUSION: In summary, these data suggest that ALOX15B is the mainly
      expressed 12/15-lipoxygenase in human macrophages and that its expression is
      induced by IL-4, LPS and hypoxia. IL-4 and IL-13 also increase the expression of
      ALOX15, however, only IL-4 stimulation seems to drive ALOX15 expression to levels
      higher than the basal expression of ALOX15B. Hence, ALOX15B may play a major role
      in human atherosclerosis.

PMID- 22980501
TI  - A multicenter study on the precision and accuracy of homogeneous assays for LDL
      cholesterol: comparison with a beta-quantification method using fresh serum
      obtained from non-diseased and diseased subjects.
AB  - BACKGROUND: Homogeneous assays for low-density lipoprotein-cholesterol (LDL-C)
      have good precision and are pretreatment-free procedures. However, their
      accuracies have been questioned, especially in diseased subjects. In this study,
      we aimed to verify whether LDL-C levels determined by homogeneous assays [LDL-C
      (H)] agree with those determined by a beta-quantification method [LDL-C (BQ)] in
      fresh clinical samples. METHODS: We determined LDL-C levels in 49 non-diseased
      and 124 diseased subjects whose triglyceride (TG) levels were less than 11.29
      mmol/L (1000 mg/dL) using 12 homogeneous assays and a BQ method simultaneously.
      RESULTS: In total, 30.6% of non-diseased subjects and 46.0% of diseased subjects
      were in the postprandial state. The maximum inter- and intra-assay CVs were 1.8%
      and 1.5%, and 8 reagents had a CV of 1.0% or less. The mean bias ranged from 
      0.5% to 1.8% for non-diseased subjects and from -0.7% to 1.6% for diseased
      subjects. For non-diseased subjects, all but one reagent achieved the National
      Cholesterol Education Program (NCEP) total error requirement in more than 90% of
      samples. However, for diseased subjects, the number of reagents that met this
      requirement was low. With some reagents, LDL-C (H) was higher than LDL-C (BQ),
      especially in subjects with hypertriglyceridemia. While for other reagents, the
      difference between the two methods was not associated with hypertriglyceridemia
      except for type I (n = 2) and type III hyperlipidemia (n = 1). Postprandial
      sampling was not the main factor for discordant results. CONCLUSIONS: LDL-C (H)
      agrees with LDL-C (BQ) in non-diseased subjects, but exhibits positive bias for
      subjects with hypertriglyceridemia in diseased subjects for some reagents.

PMID- 22980502
TI  - Assembly of bacteriophage 80alpha capsids in a Staphylococcus aureus expression
      system.
AB  - 80alpha is a temperate, double-stranded DNA bacteriophage of Staphylococcus
      aureus that can act as a "helper" for the mobilization of S. aureus pathogenicity
      islands (SaPIs), including SaPI1. When SaPI1 is mobilized by 80alpha, the SaPI
      genomes are packaged into capsids that are composed of phage proteins, but that
      are smaller than those normally formed by the phage. This size determination is
      dependent on SaPI1 proteins CpmA and CpmB. Here, we show that co-expression of
      the 80alpha capsid and scaffolding proteins in S. aureus, but not in E. coli,
      leads to the formation of procapsid-related structures, suggesting that a host co
      factor is required for assembly. The capsid and scaffolding proteins also undergo
      normal N-terminal processing upon expression in S. aureus, implicating a host
      protease. We also find that SaPI1 proteins CpmA and CpmB promote the formation of
      small capsids upon co-expression with 80alpha capsid and scaffolding proteins in
      S. aureus.

PMID- 22980504
TI  - Early stages of trachea healing process: (immuno/lectin) histochemical monitoring
      of selected markers and adhesion/growth-regulatory endogenous lectins.
AB  - Tracheotomy may be associated with numerous acute and chronic complications
      including extensive formation of granulation tissue. The emerging functional
      versatility of the adhesion/growth-regulatory galectins prompted us to perform a
      histochemical study of wound healing using rat trachea as model. By using non
      cross-reactive antibodies and the labelled tissue lectins we addressed the issue
      of the presence and regulation of galectin reactivity during trachea wound
      healing. Beside localization of high-molecular-weight keratin, wide-spectrum
      cytokeratin, keratins 10 and 14, alpha-smooth muscle actin, vimentin,
      fibronectin, and Sox-2, galectins -1, -2, and -3 and their reactivity profiles
      were measured in frozen sections of wounded and control trachea specimens 7, 14,
      and 28 days after trauma. A clear trend for decreased galectin-1 presence and
      increased reactivity for galectin-1 was revealed from day 7 to day 28. Sox-2
      positive cells were present after seven days and found in the wound bed.
      Interestingly, several similarities were observed in comparison to skin wound
      healing including regulation of galectin-1 parameters.

PMID- 22980503
TI  - Differential gene expression between skin and cervix induced by the E7
      oncoprotein in a transgenic mouse model.
AB  - HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer
      after 6 months of treatment with the co-carcinogen 17beta-estradiol. In untreated
      mice, E7 also induces skin tumors late in life albeit at low penetrance. These
      findings indicate that E7 alters cellular functions in cervix and skin so as to
      predispose these organs to tumorigenesis. Using microarrays, we determined the
      global genes expression profile in cervical and skin tissue of young adult K14E7
      transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein
      altered the transcriptional pattern of genes involved in several biological
      processes including signal transduction, transport, metabolic process, cell
      adhesion, apoptosis, cell differentiation, immune response and inflammatory
      response. Among the E7-dysregulated genes were ones not previously known to be
      involved in cervical neoplasia including DMBT1, GLI1 and 17betaHSD2 in cervix, as
      well as MMP2, 12, 14, 19 and 27 in skin.

PMID- 22980505
TI  - The karyotype of Holoaden luederwaldti (Anura, Strabomantidae), with report of
      natural triploidy.
AB  - The genus Holoaden includes three species described so far, but the only
      published cytogenetic data is from Holoaden bradei, with the karyotype 2n = 18,
      based on conventional staining. In the present paper we report, for the first
      time, data on chromosomes of H. luederwaldti, which presented 2n = 18 and a case
      of natural triploidy, with 2n = 3x = 27. In this sample, another karyotypic
      variation was observed due to the occurrence of two types of chromosome 8, which
      present submetacentric or subtelocentric morphologies. Homomorphic subtelocentric
      or heteromorphic condition was observed among the diploid specimens, whereas the
      triploid had one submetacentric and two subtelocentric chromosomes 8. In all
      specimens, Ag-NOR was located in the long arms of chromosomes 8, at the
      interstitial region when subtelocentric, or in the proximal region when
      submetacentric, confirmed by fluorescent in situ hybridization with the HM123
      probe. The C bands showed centromeric distribution and distribution at Ag-NOR
      site. The centromeric heterochromatin was fluorescent with DAPI staining, whereas
      the Ag- NOR displayed bright fluorescence with CMA3. Fluorescent in situ
      hybridization using a telomeric probe labelled exclusively the telomere regions.
      Although the same 2n = 18 chromosome numbers have been observed in H.
      luederwaldti and H. bradei, some differences in both karyotypes can be
      visualized, mainly with regard to the morphology of the last chromosome pairs.

PMID- 22980506
TI  - Expression of antigenic determinants of the haemagglutinin large subunit of novel
      influenza virus in insect cells.
AB  - The global outbreak of novel A/H1N1 spread in human population worldwide has
      revealed an emergency need for producing a vaccine against this virus. Current
      influenza vaccines encounter problems with safety issues and weak response in
      high-risk population. It has been established that haemagglutinin is the most
      important viral antigen to which antibody responses are directed, and recombinant
      subunit vaccines, haemagglutinin of influenza A and B viruses, have been
      considered in order to facilitate vaccine production. In the present study, we
      have focused on construction of a recombinant baculovirus encoding the large
      subunit of novel influenza virus A/H1N1 haemagglutinin. The full genome of
      haemagglutinin was cloned into pGEM-TEasy vector and sequenced. The large subunit
      of the haemagglutinin gene was amplified by PCR using specific primers and cloned
      into pFast- BacHTc donor plasmid, which was then confirmed by restriction enzyme
      analysis and sequencing and transformed into E. coli DH10Bac competent cells. The
      bacmid DNA was transfected into insect cells to produce recombinant baculovirus.
      Expression of recombinant haemagglutinin in insect cells was determined by SDS
      PAGE and immunoblotting. It has been shown that the recombinant haemagglutinin
      (rHA) obtained from the baculovirus insect cell expression system has suitable
      immunogenicity in human and can be considered as a candidate flu vac- cine. Here
      we produced large amounts of the HA1 protein of novel influenza A/H1N1 (Iranian
      isolate) in insect cells. The immunogenicity and efficacy of the recombinant HA1
      will be evaluated as a vaccine candidate and compared to the recombinant HA1
      produced in a prokaryotic system.

PMID- 22980507
TI  - Vitamin E treatment enhances erythrocyte deformability in aged rats.
AB  - The harmful effects of aging on blood rheology have been well known. These
      effects in the aging have been found to be associated with an increase in
      oxidative stress. The aim of this study was to seek whether treatment of vitamin
      E as a potent antioxidant could improve the age-related haemorheological
      abnormalities. For this purpose, male Wistar rats at the age of 3 and 24 months
      were used. The following parameters were evaluated: red blood cell (RBC)
      deformability, aggregation, plasma viscosity, vitamin E level, total oxidant
      status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI),
      and the following results were obtained. First, aging was associated with a
      decrease in RBC deformability and increase in RBC aggregation and plasma
      viscosity. Second, compared with the young group, while plasma TOS levels and OSI
      were found to be significantly increased in aged rats, there was no significant
      change in their plasma TAS level. Third, vitamin E administration produced
      significant improvement in RBC deformability and decrement in TOS and OSI values
      in aged rats with respect to young and aged control groups. We did not find any
      significant effect of vitamin E treatment on RBC aggregation in both young and
      aged rats and finally, we found a significantly lower plasma vitamin E level in
      aged rats than in young rats. In conclusion, these findings suggest that blood
      rheology impairs with age and vitamin E has ameliorating effects on age-induced
      haemorheological abnormalities especially in RBC deformability, probably by
      reducing the increased oxidative stress in old age.

PMID- 22980508
TI  - Resveratrol inhibits proliferation of primary rat hepatocytes in G0/G1 by
      inhibiting DNA synthesis.
AB  - Resveratrol is a phytoalexin that has been shown to inhibit cell proliferation of
      several cancer cell lines. In some cases this inhibition was specific for the
      transformed cells when compared with normal cells of the same tissue. To test
      whether this was the case in rat hepatocytes, we exposed primary rat hepatocytes
      in culture and transformed rat hepatic cells to this compound and studied its
      effect on cell proliferation, measuring deoxy-bromouridine incorporation and
      total DNA. We also studied the effect of resveratrol on the cell cycle of normal
      and transformed rat hepatocytes. We observed that resveratrol inhibited
      proliferation in a dose-dependent manner in both cases, with no differential
      action in the transformed cells compared to the normal ones. This compound
      arrested the cell cycle in G0/G1 in primary hepatocytes, while it arrested the
      cell cycle in G2/M in transformed cells. Transformed hepatocytes showed
      accumulation of cells in the S phase of the cell cycle.

PMID- 22980509
TI  - TRPC6 gene variants in Czech adult patients with focal segmental
      glomerulosclerosis and minimal change disease.
AB  - Blood filtration and formation of primary urine in the kidney glomerulus is
      provided by a specialized membrane called slit diaphragm located between well
      branched pedicels of podocytes. Actually, the slit diaphragm is a protein
      supercomplex, whose disruption can cause failure of renal filtration, and
      patients usually manifest nephrotic syndrome. Recently, familial forms of
      nephrotic syndrome have been described which arise from malfunction of mutated
      proteins making up the slit diaphragm. In 2005 it was found that one of the
      proteins present in this complex was non-selective cation channel TRPC6. The aim
      of this work was to screen mutations and polymorphisms of the TRPC6 gene in a
      group of 64 Czech patients with nephrotic syndrome and subsequently, on the basis
      of these data, evaluate the role of mutations in the TRPC6 gene in Czech
      population. The analysis was performed by the PCR method followed by direct
      sequencing and high-resolution melting method. We have not identified any
      mutations in our group of patients. Two additional single nucleotide
      polymorphisms - p.P15S and p.A404V - were detected along with nucleotide changes
      that did not result in amino acid changes and with a few intronic changes. P.P15S
      heterozygotes were more frequent in patients with steroid-resistant FSGS than in
      steroid- sensitive patients (29 % versus 12.1 %). To conclude, we did not find
      any probable disease-causing mutation in the TRPC6 gene in the cohort of 64 Czech
      patients. The p.P15S polymorphism might have some influence on the therapeutic
      response of FSGS patients.

PMID- 22980510
TI  - Validation of adenosine triphosphate to audit manual cleaning of flexible
      endoscope channels.
AB  - BACKGROUND: Compliance with cleaning of flexible endoscope channels cannot be
      verified using visual inspection. Adenosine triphosphate (ATP) has been suggested
      as a possible rapid cleaning monitor for flexible endoscope channels. There have
      not been published validation studies to specify the level of ATP that indicates
      inadequate cleaning has been achieved. OBJECTIVE: The objective of this study was
      to validate the Clean-Trace (3M Inc, St. Paul, MN) ATP water test method for
      monitoring manual cleaning of flexible endoscopes. METHODS: This was a simulated
      use study using a duodenoscope as the test device. Artificial test soil
      containing 10(6) colony-forming units of Pseudomonas aeruginosa and Enterococcus
      faecalis was used to perfuse all channels. The flush sample method for the
      suction-biopsy (L1) or air-water channel (L2) using 40 and 20 mLs sterile reverse
      osmosis water, respectively, was validated. Residuals of ATP, protein,
      hemoglobin, and bioburden were quantitated from channel samples taken from
      uncleaned, partially cleaned, and fully cleaned duodenoscopes. The benchmarks for
      clean were as follows: <6.4 MUg/cm(2) protein, <2.2 MUg/cm(2) hemoglobin, and <4
      log10 colony-forming units/cm(2) bioburden. RESULTS: The average ATP in clean
      channel samples was 27.7 RLUs and 154 RLUs for L1 and L2, respectively (<200 RLUs
      for all channels). The average protein, hemoglobin, and bioburden benchmarks were
      achieved if <200 RLUs were detected. If the channel sample was >200 RLUs, the
      residual organic and bioburden levels would exceed the acceptable benchmarks.
      CONCLUSION: Our data validated that flexible endoscopes that have complete manual
      cleaning will have <200 RLUs by the Clean-Trace ATP test.

PMID- 22980511
TI  - Haemophilus influenzae as an airborne contamination in child day care centers.
AB  - BACKGROUND: The aim of this study was to assess the exposure of children to
      airborne Haemophilus influenzae in day care centers. METHODS: Air samples were
      taken using an Andersen impactor in 32 rooms designed for children stay. The
      concentrations of airborne bacteria were calculated as colony forming units (CFU)
      (growing on trypticase soy agar) per cubic meter of air (CFU/m(3)). The
      compositions of bioaerosol were determined on blood trypticase soy agar and
      Haemophilus selective agar. Isolated strains were identified using API NH strips
      and apiweb software. The antibiotic resistance of H influenzae strains was
      determined by the disk diffusion method. RESULTS: Compared with the proposed
      criteria for microbiologic quality of indoor air, the rooms were characterized by
      the very high bacterial contamination of the air. The prevailing component of
      bacterial aerosol was gram-positive cocci. Airborne H influenzae strains were
      found in 25% of the investigated rooms and were mostly classified as biotype II
      (33%). CONCLUSION: It may be accepted that the exposure to airborne H influenzae
      is typical of child day care centers in contrast to indoor environments with
      older population. Child day care center contribute to the expansion of H
      influenzae in human population via air. Generally, airborne H influenzae isolates
      from the investigated child day care centers were susceptible to older
      antibiotics such as ampicillin and amoxicillin-clavulanic acid.

PMID- 22980512
TI  - Impact of chlorhexidine-impregnated washcloths on reducing incidence of
      vancomycin-resistant enterococci colonization in hematology-oncology patients.
AB  - BACKGROUND: Daily skin cleansing with washcloths impregnated with chlorhexidine
      gluconate (CHG) of patients in intensive care unit is associated with reduction
      in incidence of vancomycin-resistant Enterococci (VRE) acquisition. This study
      describes the impact on incidence of VRE colonization after the implementation of
      daily skin cleansing with 2% CHG-impregnated washcloths in hematology-oncology
      patients. METHODS: In this before-and-after study, we compared the incidence rate
      of VRE colonization during the baseline period (where routine soap-and-water
      bathing was used) with the intervention period where patients were cleansed with
      2% CHG-impregnated washcloths. RESULTS: Acquisition of VRE decreased from 7.8% in
      the baseline to 3.8% in the intervention period (relative risk, 0.48, 95%
      confidence interval [CI], 0.21-1.09; P = .07). The crude relative rate of
      acquisition during the intervention period compared with the baseline period was
      0.53 (95% CI, 0.23-1.23; P = .13). Patients who had been a roommate of a patient
      subsequently found to have VRE were at a significantly increased risk for
      acquiring VRE (hazard ratio, 18.8, 95% CI, 5.37-66.15; P < .001). However,
      patients admitted to the same bed number of previously known VRE-colonized
      patient were not at increased risk of VRE acquisition (hazard ratio, 0.37, 95%
      CI, 0.11-1.22; P = .10). CONCLUSION: We did not observe a statistically
      significant reduction in the rate of VRE colonization in association with the use
      of 2% CHG-impregnated washcloths among hematology-oncology patients.

PMID- 22980513
TI  - The reduction of risk in central line-associated bloodstream infections:
      knowledge, attitudes, and evidence-based practices in health care workers.
AB  - BACKGROUND: We set out to acquire information about the knowledge, attitudes, and
      evidence-based practices associated with the insertion and maintenance of central
      vascular catheters (CVC) for the prevention of central line-associated
      bloodstream infections (CLABSI). METHODS: We selected all health care workers
      (HCW) in all units using CVCs in the Calabria region of Italy. RESULTS: Correct
      answers about the knowledge of physicians and nurses ranged from 43% to 72.9% and
      were significantly higher in respondents who worked in intensive care unit (ICU)
      wards in hospitals that had a written policy about CVC maintenance and had active
      formal training. Respondents' attitudes toward general aspects of CLABSI
      prevention were very positive and were significantly higher for HCWs working in
      regional general hospitals, practicing in ICU wards, and having appropriate
      knowledge. Concerning HCWs, 83.9% reported that, if patients had any
      manifestations suggesting local or bloodstream infection, the dressing was
      removed for assessment purposes; this practice was significantly more likely to
      occur in HCWs having appropriate knowledge and positive attitudes and who worked
      in hospitals with a written policy about CVC maintenance. CONCLUSION: The study
      demonstrated that written policies, formal training, and years of experience
      contributed to an increase in knowledge, practice, and positive attitudes toward
      CLABSI prevention. In addition the paper demonstrates how great this need is,
      having reported many non-evidence-based practices still continuing despite new
      evidence.

PMID- 22980514
TI  - Sustained reductions in urinary catheter use over 5 years: bedside nurses view
      themselves responsible for evaluation of catheter necessity.
AB  - BACKGROUND: Multiple approaches are needed to improve urinary catheter use and
      sustain compliance with the appropriate indications for catheter use. METHODS: We
      evaluated the effect of 3 interventions over 5 years: a nurse-driven
      multidisciplinary effort for early urinary catheter removal, an intervention in
      an emergency department to promote appropriate placement, and twice-weekly
      assessment of urinary catheter prevalence with periodic feedback on performance
      for nonintensive care units. We also assessed the views of bedside nurses, case
      managers, and nurse managers with respect to appropriate catheter use, how often
      need is assessed, and who they consider responsible for the evaluation of urinary
      catheter need. RESULTS: There was a significant reduction in urinary catheter use
      from 17.3%-12.7% during the 5-year period (linear regression with time as
      independent variable, R(2), 0.61; P < .0001). Of bedside nurses responding to the
      questionnaire, 222 of 227 (97.8%) identified themselves as responsible or as
      sharing the responsibility for catheter necessity evaluation, 223 of 229 (97.4%)
      were confident in their knowledge, and 166 of 222 (74.8%) viewed physicians as
      receptive to their requests for catheter removal >70% of the time. CONCLUSIONS: A
      multifaceted approach to promote appropriate urinary catheter use is associated
      with sustained reductions in catheter use. Bedside nurses view themselves
      responsible for the evaluation of catheter presence and need.

PMID- 22980515
TI  - Time lag for posting transmission-based isolation precaution signs.
AB  - BACKGROUND: Rapid identification and isolation of patients colonized or infected
      with virulent pathogens is essential to minimize risk of exposure to other
      patients, visitors, and health care workers. OBJECTIVE: Our objective was to
      determine the time lag between when a patient is identified as requiring
      isolation precautions and when an isolation sign is posted outside of their room.
      METHODS: Patients requiring assessment of isolation precautions because of a new
      positive culture, readmission, or transfers within the institution were
      identified through an electronic surveillance system. Observers recorded the
      presence of isolation signs at the patient's door at time (T) 0hr, T2hr, T4hr,
      T24hr, and T48hr or until an isolation sign was posted. RESULTS: The majority of
      patients was adults in nonintensive care units. Isolation signs were present for
      79.0% of the patients at T0hr and increased to 83.8% by T48hr. No difference was
      seen between the unit type or indications for isolation. The most common
      organisms for which isolation was indicated were influenza and resistant
      enterococci, Staphylococcus aureus; isolation sign postings at T0hr were 87.9%,
      85.7%, and 80.7%, respectively. There was a significant difference seen in
      compliance among the adult (82.8%) and pediatrics (66.7%) sites (P = .0268).
      CONCLUSION: Isolation precautions are indicated to prevent transmission of
      virulent pathogens; however, their implementation in a timely manner can be
      challenging. In this study, approximately 20% of patients for whom isolation was
      needed had no sign posted within the first 24 hours, and there were only minimal
      increases thereafter. Simple processes are needed for early identification of
      patients, communication of the protective equipment needed, and continuous
      monitoring of adherence to guidelines.

PMID- 22980516
TI  - BCL-G as a new candidate gene for immune responses in pigs: bioinformatic
      analysis and functional characterization.
AB  - BCL-G, also known as Bcl2-like14, is a unique member of the Bcl-2 family that
      plays an important role in regulating apoptosis in humans. In the present study,
      we assessed the biological activities of porcine BCL-G (pBCL-G). The open reading
      frame (ORF) of pBCL-G covered 990 bp and encoded 329 amino acids. The genomic
      structure of the pBCL-G gene was also determined. The deduced amino acid sequence
      of the pBCL-G cDNA was highly identical to homologs in other species.
      Furthermore, domain prediction showed that pBCL-G protein contains BH2 and BH3
      domains, which are typical domains of the Bcl-2 family. Phylogenetic analysis
      indicated that BCL-G may function differently among species. Subcellular
      localization analysis showed that GFP-pBCL-G fusion protein is distributed in the
      nucleus and cytoplasm. Flow cytometric analysis proved that pBCL-G is a pro
      apoptotic factor. This study is useful for understanding pBCL-G and offers a
      potential molecular model for the investigation of diseases related to human BCL
      G.

PMID- 22980517
TI  - Exercise-induced anaphylaxis: A clinical view.
AB  - Exercise-induced anaphylaxis (EIA) is a distinct form of physical allergy. The
      development of anaphylaxis during exertion often requires the concomitant
      exposure to triggering factors such as intake of foods (food dependent exercise
      induced anaphylaxis) or drugs prior to exercise, extreme environmental
      conditions. EIA is a rare, but serious disorder, which is often undetected or
      inadequately treated. This article summarizes current evidences on
      pathophysiology, diagnosis and management. We reviewed recent advances in factors
      triggering the release of mediators from mast cells which seems to play a
      pathogenetic role. A correct diagnosis is essential to avoid unnecessary
      restricted diet, to allow physical activity in subjects with EIA dependent from
      triggering factors such as food, and to manage attacks. An algorithm for
      diagnosing EIA based on medical history, IgE tests and exercise challenge test
      has been provided. In the long-term management of EIA, there is a need for
      educating patients and care-givers to avoid exposure to precipitating factors and
      to recognize and treat episodes. Future researches on existing questions are
      discussed.

PMID- 22980518
TI  - Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate
      synthase as a helpful tool to better characterise the patients.
AB  - Mitochondrial DNA depletion syndrome (MDS) is a clinically heterogeneous group of
      mitochondrial disorders characterised by a quantitative reduction of the
      mitochondrial DNA copy number. Three main clinical forms of MDS: myopathic,
      encephalomyopathic and hepatocerebral have been defined, although patients may
      present with other MDS associated clinical symptoms and signs that cover a wide
      spectrum of onset age and disease. We studied 52 paediatric individuals suspected
      to have MDS. These patients have been divided into three different groups, and
      the appropriate MDS genes have been screened according to their clinical and
      biochemical phenotypes. Mutational study of DGUOK, MPV17, SUCLA2, SUCLG1 and POLG
      allowed us to identify 3 novel mutations (c.1048G>A and c.1049G>T in SUCLA2 and
      c.531+4A>T in SUCLG1) and 7 already known mutations in 10 patients (8 families).
      Seventeen patients presented with mtDNA depletion in liver or muscle, but the
      cause of mtDNA depletion still remains unknown in 8 of them. When possible, we
      quantified mtDNA/nDNA and CS activity in the same tissue sample, providing an
      additional tool for the study of MDS. The ratio (mtDNA/nDNA)/CS has shed some
      light in the discrepant results between the mtDNA copy number and the enzymatic
      respiratory chain activities of some cases.

PMID- 22980519
TI  - The real-time display of data, the miniaturization of current systems and their
      reliability make possible their long-term use with ambulatory patients.

PMID- 22980520
TI  - Real-time continuous glucose monitoring (CGM) integrated into the treatment of
      type 1 diabetes: consensus of experts from SFD, EVADIAC and SFE.

PMID- 22980521
TI  - A prospective pilot study of repetitive transcranial magnetic stimulation for
      gait dysfunction in vascular parkinsonism.
AB  - OBJECTIVE: Vascular Parkinsonism (VP) causes significant gait dysfunction in
      patients who otherwise have good lower limb strength. Its pathophysiology is not
      clearly understood, and current treatment with physical therapy remains
      unsatisfactory. The study explores repetitive transcranial magnetic stimulation
      (rTMS) as a potential new and safe therapy for VP. MATERIALS AND METHODS: We
      prospectively applied 5 Hz rTMS treatment to 5 patients who satisfied all the
      criteria for VP. Repetitive TMS was performed on 5 consecutive days and patients
      were assessed on (1) timed 10 m walk (T10MW), (2) Unified Parkinson's Disease
      Rating Scale (UPDRS) motor subsection, (3) Clinician's Global Impression of
      Change (CGIC), and (4) Patient's Global Impression of Change (PGIC), for up to 6
      weeks post-rTMS. RESULTS: All the outcome measures were found to have improved
      ratings post-rTMS when compared with baseline, and were statistically
      significant. The T10MW showed significant improvement at 4 weeks post-rTMS with a
      trend towards improvement at 2 weeks post-rTMS. The UPDRS motor subscores was
      significantly reduced at 2 weeks, 4 weeks and 6 weeks post-rTMS. The PGIC and
      CGIC scores were significantly better post-rTMS. The treatment was well-tolerated
      and all patients completed the study. CONCLUSION: This study demonstrated for the
      first time that 5 sessions of rTMS could improve gait in a measurable way for up
      to 6 weeks without any significant side-effects. Repetitive TMS could be a
      potentially useful adjunct in rehabilitation of VP patients and further research
      is warranted.

PMID- 22980522
TI  - Combined toxicity of penicillin and aspirin therapy may elicit bilateral
      vestibulopathy.

PMID- 22980523
TI  - Call-Fleming syndrome associated with convexity subarachnoid hemorrhage.

PMID- 22980524
TI  - Paroxysmal exertion-induced dystonia secondary to Erdheim-Chester disease.

PMID- 22980525
TI  - Screening for symptoms of obstructive sleep apnea in children with severe
      craniofacial anomalies: assessment in a multidisciplinary unit.
AB  - OBJECTIVE: To assess the incidence of airway obstruction symptoms and the
      presence of obstructive sleep apnea in children with severe craniofacial
      anomalies by a proactive screening program using a standard questionnaire and
      cardiorespiratory polygraphy. PATIENTS AND METHODS: Children with severe
      craniofacial anomalies referred to our paediatric airway unit from February 2001
      to June 2011 were eligible to be included in this retrospective, single centre
      study. Symptoms of airway obstruction were proactively investigated using the
      shorter version of the Pediatric Sleep Questionnaire (PSQ). Obstructive sleep
      apnea was assessed by means of cardiorespiratory polygraphy. Demographic data and
      reason for referral were also recorded. Primary outcomes were the prevalence of
      symptoms of airway obstruction and OSA. RESULTS: 44 children (24 girls) with
      severe craniofacial anomalies (15 Crouzon, 13 Apert, 9 Goldenhar, 5 Treacher
      Collins, 2 Pfeiffer) were included, at a mean age of 5 years (range 8 months to
      14 years). Reason for referral was routine follow up in 30 patients and overt OSA
      symptoms and signs in the remaining 14. PSQ results showed symptoms of airway
      obstruction in 82% of patients, being snoring the most frequent symptom (64.1%)
      followed by apneas (33.3%). Polygraphic studies showed inconclusive results in 8
      children (18.2%), normal apnea-hypopnea index (AHI) in 16 (36.4%), mild
      obstructive sleep apnea in 9 (20.4%), moderate in 4 (9.1%) and severe obstructive
      sleep apnea in 7 (15.9%). CONCLUSIONS: Children with craniofacial anomalies have
      a high prevalence of symptoms of airway obstruction and obstructive sleep apnea
      that support a proactive screening strategy in this highly selected population.

PMID- 22980526
TI  - Criteria for Guillain-Barre syndrome: additional insights from clinico
      pathological studies.

PMID- 22980527
TI  - Do negative emotional factors have independent associations with excess
      adiposity?
AB  - OBJECTIVE: Taken in isolation, depression, anxiety, and hostility/anger have been
      shown to predict obesity. It is unknown whether these negative emotional factors
      are associated with adiposity, independently of each other. The objective of this
      review was to determine whether negative emotional factors have independent
      associations with adiposity. METHODS: We searched for observational studies
      examining adiposity and two or more negative emotional factors. Studies which
      examined a negative emotional factor using analyses which controlled for other
      emotional factor(s) were selected for the review. RESULTS: Three prospective and
      11 cross-sectional studies met our inclusion/exclusion criteria. Of these
      investigations, 64% indicated that depression had positive associations with
      adiposity, independent of anxiety or hostility, and 56% indicated that anxiety
      had independent associations with adiposity. Only 33% of studies found
      independent associations for hostility and adiposity; however, far fewer studies
      were available. CONCLUSION: Depression and anxiety have independent associations
      with excess adiposity when controlling for other emotional factors. Additional
      studies are needed to determine whether hostility/anger is independently
      associated with excess adiposity. These results have implications for the design
      of effective obesity prevention programs.

PMID- 22980528
TI  - The relative importance of psychosocial factors in arthritis: findings from
      10,509 Australian women.
AB  - OBJECTIVE: To determine the relative importance of psychosocial factors in
      arthritis diagnosis in an ageing cohort of Australian women. METHODS: This study
      focused on 10,509 women from the 1946-1951 cohort who responded to questions on
      arthritis in the fifth mailed population-based survey of the Australian
      Longitudinal Study on Women's Health conducted in 2007. RESULTS: Arthritis was
      characterised by widespread psychosocial concerns, particularly relating to
      chronic stress and poor mental health. Univariate analyses revealed that in
      comparison to women without stress, women with moderate/high stress levels had a
      2.5-fold increase in reporting arthritis. Experiencing ongoing negative
      interpersonal life events concerning illness of a family member/close friend and
      relationship difficulties was also associated with a 1.4-fold increase in the
      reporting of arthritis. Likewise, significantly reduced levels of optimism and
      perceived social support were noted (all associations p<.001). Psychiatric
      diagnosis was also associated with a two-fold increase in having arthritis
      (p<.001). Following adjustment for behavioural, demographic and health-related
      characteristics, anxiety was the only psychosocial factor associated with
      arthritis (OR=1.4, 95% CI=1.2, 1.7; p<.001). CONCLUSION: This study examined,
      epidemiologically, the relative importance of psychosocial factors in arthritis
      in an ageing cohort of Australian women. The findings from this population-based
      study indicate that women with arthritis are more likely to report a range of
      psychosocial-related problems, particularly with regard to chronic stress
      perception and anxiety. Longitudinal analyses are required to examine the
      processes by which stress and psychosocial factors may contribute to arthritis
      risk and poor adaptation in terms of health-related quality of life.

PMID- 22980529
TI  - PTSD following childbirth: a prospective study of incidence and risk factors in
      Canadian women.
AB  - OBJECTIVE: The goals of the present study were to estimate the incidence and
      course of full and partial Post-Traumatic Stress Disorder (PTSD) following
      childbirth and to prospectively identify factors associated with the development
      of PTSD symptoms at 1month following childbirth. METHODS: The sample comprised
      308 women, with assessments at four time points: 25-40weeks gestation, 4-6weeks
      postpartum, 3 and 6months postpartum. Current and prior PTSD were assessed by the
      Structured Clinical Interview for DSM-IV (SCID-I) and the Modified PTSD Symptom
      Scale Self-Report (MPSS-SR). RESULTS: Incidence rates of PTSD varied according to
      time of measurement and instrument used, with higher rates of full and partial
      PTSD using the MPSS-SR at 1month postpartum (7.6% and 16.6%, respectively).
      Multivariate logistic regression showed that higher anxiety sensitivity (OR=1.75;
      95% CI=1.19-2.57, p=.005), history of sexual trauma (OR=2.81; 95% CI=1.07-7.37,
      p=.036), a more negative childbirth experience than expected (OR=0.96; 95%
      CI=0.94-0.98, p=.001), and less available social support at 1month postpartum
      (OR=0.40; 95% CI=0.17-0.96, p=.041) independently predicted full or partial PTSD
      at 1month following childbirth. CONCLUSION: Our results indicate that a history
      of sexual trauma and anxiety sensitivity can increase the probability of
      developing PTSD after childbirth. The findings highlight the importance of
      screening and providing more tailored services for women at high risk.

PMID- 22980530
TI  - Modern health worries and visits to the general practitioner in a general
      population sample: an 18month follow-up study.
AB  - OBJECTIVE: Modern health worries (MHW) are concerns about health risks from
      features of modern life (e.g. additives in food, contaminated water supply, drug
      resistant bacteria, etc.). We investigated the role of MHW for care seeking for
      all purposes at the general practitioner (GP) and studied the role of
      neuroticism, symptoms of anxiety and somatization, other health anxiety, self
      rated health, age, education and gender on the association between MHW and care
      seeking. METHODS: A representative sample from eight GPs (n=5068) completed a
      baseline questionnaire on MHW, symptoms of health and personality, and was
      followed for visits to the GP for the next 18months in the registers from the GP.
      RESULTS: Modern health worries were common, and higher levels were seen among
      women and in higher age. Care seeking at the GP was associated with MHW, and this
      association was maintained after adjusting for age, gender, neurotic traits,
      symptoms of anxiety, somatization, other health anxieties and self-rated health.
      CONCLUSION: Over and beyond health related factors and personality, MHW had an
      independent role for future visits to the GP in the magnitude of 20% more visits
      among the participants in the highest quartile of the MHW-scale.

PMID- 22980531
TI  - Characteristics of suicide among diabetes patients: a population based study of
      suicide victims in Northern Finland.
AB  - OBJECTIVE: Recent case reports of insulin suicides have raised the need to study
      in detail the suicides among diabetes patients. METHODS: The data consisted of
      2489 suicides (2030 men, 459 women) in Northern Finland during 1988 to 2010. The
      suicide victims with hospital-treated type 1 (n=27) or type 2 diabetes (n=51)
      were compared with those without diabetes (n=2411). RESULTS: Of all suicide
      victims, 3.1% had diabetes (34.6% type 1 and 65.4% type 2 diabetes). 24.0% of
      victims with type 2 diabetes were under the influence of alcohol when they died
      from suicide, while the proportion was 44.4% in type 1 diabetes and 46.6% in
      victims without diabetes (P=0.007). Compared to those with type 2 diabetes or
      without diabetes, victims with type 1 diabetes had suffered more commonly from
      depression (44.4%, 23.5%, 19.9%, respectively) (P=0.006) and chosen self
      poisoning as suicide method (48.1%, 31.4%, and 18.0%) (P<0.001). In victims with
      type 1 diabetes insulin as a suicide method covered half of the self-poisoning
      cases, while the proportion in type 2 diabetes was 13%. CONCLUSION: We suggest
      that physicians who treat diabetes patients should evaluate co-occurring
      depression and substance abuse, both of which are major risk factors of suicide.

PMID- 22980532
TI  - Multiple sclerosis relapses and depression.
AB  - OBJECTIVE: The expression of clinically significant depression symptoms during
      and post multiple sclerosis (MS) relapse was investigated. The point prevalence
      of possible depression during a confirmed MS relapse and at 2 and 6months post
      relapse was examined and the influence of disability on the time course of
      depression symptoms post-relapse determined. METHODS: 132 sequential patients
      were recruited from an open access relapse clinic. Clinical data including
      disability (Expanded Disability Status Scale: EDSS) and depression symptoms
      (Hospital Anxiety and Depression Scale depression subscale: HADS-D) were recorded
      at 0, 2 and 6months post-relapse. RESULTS: Prevalence of possible depression
      (HADS-D score of>=8) was 44.5% during relapse, reducing to 29.2% at 2months and
      34.4% at 6months post-relapse. HADS-D scores were significantly lower at follow
      up than during relapse. Possible depression at relapse was significantly related
      to a higher likelihood of possible depression at 2month follow-up (OR 12.12) and
      improvement in EDSS was related to a lower likelihood (OR 0.51). EDSS at relapse
      (OR 1.47) and possible depression at relapse (OR 11.87) were significantly
      associated with possible depression 6months post-relapse. CONCLUSIONS: High rates
      of possible depression were observed during relapse. Although depression scores
      reduced significantly post-relapse, rates of possible depression at follow-ups
      remained high. The results suggest that although improvements in disability may
      influence depression symptoms over the short-term, once depression symptoms are
      elevated at relapse then depression symptoms become persistent. Further studies
      are required on the relationship between relapses and depression and whether
      targeted psychological interventions are beneficial.

PMID- 22980533
TI  - Do negative aspects of social relations influence fatigue? A cross-sectional
      study on a non-clinical sample of middle-aged Danish men.
AB  - OBJECTIVE: Fatigue is a common complaint among young and old adults and may be
      associated with negative aspects of social relations. Hence, the purpose of this
      study was to explore the association between demands from and conflicts with
      different sources of social relations and fatigue. METHODS: The study was based
      on sub-populations of the 6292 members of the Danish Metropolit Cohort. The
      cohort comprises men born in 1953 in the Copenhagen Metropolitan area who
      participated in a questionnaire survey in 2004. Data were analysed using chi(2)
      tests and multivariable logistic regression. RESULTS: The results showed that
      demands from and conflicts with children were independently associated with
      fatigue in a dose-response pattern. The adjusted odds ratio for fatigue was 1.48
      (95% CI: 1.01-2.17) when the men experienced frequent demands from children and
      1.89 (95% CI: 1.17-3.06) when they had frequent conflicts with their children.
      Crude analyses of demands from or conflicts with spouse, relatives or friends,
      respectively showed associations with fatigue compared to no demands or no
      conflicts. However, adjustment for depression and physical chronic disease
      cancelled out these associations. CONCLUSION: We concluded that middle-aged
      Danish men, who had frequent negative social interactions with their children,
      more frequently experienced fatigue. However, negative social interactions with
      spouse, relatives or friends were not associated with fatigue.

PMID- 22980535
TI  - Personality traits and life dissatisfaction as risk factors for disability
      pension due to low back diagnoses: a 30-year longitudinal cohort study of Finnish
      twins.
AB  - OBJECTIVE: Little is known about the association of mild symptoms and mental well
      being with risk of disability pension (DP) due to somatic diagnoses, even less
      for DP due to low back diagnoses (LBD). Moderate genetic influences on
      personality traits, life dissatisfaction and DP exist suggesting that shared
      genetic influences may underlie these associations. One can control for familial
      confounding (genetics and family environment) by examining twins. This twin study
      aimed to investigate personality traits and life dissatisfaction as predictors
      for DP due to LBD accounting for familial confounding. METHODS: Data on 24043
      twins aged 18-65year in a baseline survey in 1975 was followed up from national
      DP register data until 2004. Personality traits were assessed using the short
      version of the Eysenck Personality Inventory and life dissatisfaction was
      measured with a four item scale on levels of interest, happiness, easiness, and
      loneliness of life. Cox proportional hazards regression was used to calculate
      hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: DP due to LBD was
      granted to 537 individuals during the follow-up. Each one unit increase in life
      dissatisfaction (HR 1.06; 95%CI 1.03, 1.10) and neuroticism (1.07; 1.03, 1.10)
      but not extroversion was significantly associated with an elevated risk for DP
      due to LBD. These associations with life dissatisfaction and neuroticism remained
      when socioeconomic status, education, and marital status were taken into account,
      and demonstrated an independence from familial confounding. CONCLUSION: Life
      dissatisfaction and neuroticism seems to be early, perhaps causal risk factors
      for DP due to LBD.

PMID- 22980534
TI  - The longitudinal relationship between parental reports of asthma and anxiety and
      depression symptoms among two groups of Puerto Rican youth.
AB  - OBJECTIVES: This study aims to examine the relationship between parental reports
      of child asthma and levels and slopes of anxiety and depression symptoms among
      two contrasting groups of Puerto Rican youth, and to determine whether asthma is
      a special risk above and beyond parents' reports of other youths' medical
      conditions. METHODS: Two probability samples of youth in San Juan and Caguas,
      Puerto Rico (n=673) and in the south Bronx, New York (n=598), and their
      caretakers were interviewed in three yearly assessments. Parental reports of
      their children's asthma during each assessment were used to indicate whether
      youth had intermittent (PR=34%, NY=23%) or persistent (PR=7%, NY=16%) asthma.
      Youths' depression and anxiety symptoms were assessed using self reports to the
      DISC-IV. Information on youths' medical comorbidity was gathered through parental
      reports. RESULTS: Multilevel analyses adjusting for comorbid medical conditions
      indicated that parental reports of youths' intermittent and persistent asthma
      were related to higher levels, but similar slopes, of anxiety and depression
      among youth in New York. In Puerto Rico, youth with persistent asthma experienced
      less improvement in anxiety over time than youth without asthma, but no other
      associations were found. CONCLUSION: Having asthma, based on parental reports,
      represents a risk factor for Puerto Rican youths' internalizing symptoms, even
      after adjusting for comorbid medical conditions. This risk is more pronounced
      among youth living in New York, which highlights the importance of considering
      the social context in which youth develop and minority status when examining
      associations between physical health risk factors and mental health.

PMID- 22980536
TI  - Perfectionism and health functioning in women with fibromyalgia.
AB  - OBJECTIVE: The purpose of this study was to examine the associations between
      dimensions of perfectionism (self-oriented, other-oriented, and socially
      prescribed perfectionism) and health functioning in a sample of 489 women with
      fibromyalgia. METHODS: Hierarchical multiple regression was used to determine
      whether dimensions of perfectionism were differentially associated with health
      functioning among women with fibromyalgia after accounting for broader
      personality traits related to both perfectionism and health functioning. RESULTS:
      The results confirmed that both socially prescribed perfectionism and self
      oriented perfectionism were associated with lower health functioning. Moreover,
      these associations were found after accounting for the effects of
      conscientiousness, extraversion, and neuroticism. The findings involving self
      oriented perfectionism were particularly complex and suggested that moderate self
      oriented perfectionism may be somewhat adaptive, but too much or too little self
      oriented perfectionism is associated with substantial reductions in health
      functioning among women with fibromyalgia. CONCLUSION: Collectively, these
      findings clarify that overall levels of perfectionism are not elevated among
      women with fibromyalgia, but those women who are exceptionally high in levels of
      self-oriented perfectionism or high in socially prescribed perfectionism are
      particularly likely to suffer lower health functioning. These results suggest
      that perfectionism should be specifically assessed and targeted for intervention
      among women with fibromyalgia and there should be a particular emphasis on the
      pressure to meet perceived or actual expectations imposed on the self.

PMID- 22980537
TI  - Somatic expressions of grief and psychosomatic illness in the works of William
      Shakespeare and his coevals.
AB  - OBJECTIVE: To find out if Shakespeare, famed for his insights into human nature,
      is exceptional in how much his characters express grief through somatic symptoms
      and signs, and by physical illness. METHODS: The texts of all large-scale works
      currently attributed to Shakespeare (39 plays, 3 long narrative poems) were
      systematically searched for bodily changes and for evidence of grief as
      dominating the character's emotional state at the time. The findings were
      compared with those from a search of 46 works, similar in genre, by 15 prominent
      playwrights active at the same time as Shakespeare. RESULTS: In Shakespeare 31
      different grief-associated symptoms or signs were found, in 140 instances. They
      are present in all but two of his plays and long poems and involve most systems
      of the body. With non-Shakespearean writers there were 26 kinds, 132 instances.
      Twenty-two changes are common to both groups, including fainting, death (sudden
      or after a decline), and wrinkled face, and symptoms such as malaise, fatigue,
      awareness of the heart-beat, and anorexia. Ten somatic expressions of grief were
      found only in Shakespeare, including hyperventilation, hair turning white and
      premature childbirth. Four were found only in his contemporaries but were trivial
      or unconvincing. Deaths and non-fatal illnesses are prevalent in Shakespeare.
      CONCLUSIONS: Grieving Shakespearean characters exhibit many somatic symptoms and
      signs and a wide range of psychosomatic illnesses. This panoply of psychosomatic
      phenomena may be an artistic artefact but it also confirms that Shakespeare's
      empathy with grieving humanity was unrivalled.

PMID- 22980538
TI  - Nocturnal masseter muscle activity is related to symptoms and somatization in
      temporomandibular disorders.
AB  - OBJECTIVE: Temporomandibular disorders (TMD) have often been related to sleep
      bruxism and elevated nocturnal masseter muscle activity (NMMA). However, previous
      studies have revealed controversial results, and the role of somatization,
      depression and anxiety has not been studied in this context. The aim of this
      study was to investigate the association between NMMA and pain intensity, TMD
      related symptoms, somatoform symptoms, depression, and anxiety in chronic TMD.
      METHODS: Thirty-six subjects with chronic painful TMD, 34 subjects with pain free
      bruxism, and 36 healthy controls recorded their nocturnal masseter muscle
      activity during three consecutive nights with portable devices. In addition,
      participants completed pain diaries and questionnaires. Diagnoses were
      established using the research diagnostic criteria for TMD. RESULTS: Subjects
      with chronic TMD reported a reduced general health state (p<.001), higher levels
      of somatoform symptoms (p<.001), depression (p<.05), and anxiety (p<.001)
      compared to control subjects with or without sleep bruxism. The amount of NMMA
      did not differ significantly between the groups. In subjects with TMD, pain
      intensity was not related to NMMA. However, higher NMMA was related to higher
      intensity of jaw related symptoms such as headache or tinnitus, and higher
      somatization in general. CONCLUSION: Chronic TMD is associated with elevated
      levels of psychopathology. These findings suggest a common link between NMMA,
      somatization, and symptom intensity in chronic TMD.

PMID- 22980539
TI  - Increased number of activated T cells in lymphocyte subsets of maltreated
      children: data from a pilot study.
AB  - OBJECTIVE: Maltreatment in childhood has been related to enduring changes in the
      immune system of adults, such as increased cell-mediated immune response.
      PURPOSE: Due to the lack of data in children, this study examined lymphocyte
      subset numbers and distribution during youth. METHODS: In 27 cases of 42 healthy
      but maltreated children, fully participating at follow-up 1-3years after the
      intervention of child protection team, and 19 cases of previously matched
      controls, analysis of blood samples by fluorescent activated cell sorter was
      consented. RESULTS: With regard to age references, total lymphocyte counts were
      aberrant in maltreated children but not in controls. When compared to controls,
      the percentages and absolute numbers of activated (HLA-DR+) CD4+helper and
      CD8+cytotoxic T cells were significantly higher in maltreated children.
      CONCLUSIONS: According to the typical distribution of HLA-DR+cells we assumed an
      increased stimulated cell-mediated immune function in maltreated children.

PMID- 22980540
TI  - The Transplanted Organ Questionnaire: a validation study.
AB  - OBJECTIVE: The transplanted organ is a key element of the recipient's daily life.
      But its representations are neither spontaneously expressed by patients, nor
      taken into account by transplantation professionals. Our objective was to assess
      specifically the transplanted organ representations in liver transplant
      recipients. METHODS: In a prospective cohort study, 134 liver transplanted (LT)
      patients were assessed using the Transplanted Organ Questionnaire (TOQ), a new
      specifically designed questionnaire, fulfilled 3, 6, 12, 24, and 36months post
      LT. RESULTS: The TOQ comprised three dimensions, explaining 44% of the total
      variance: Donor (21.3%) measuring the recipients' concerns about the donor,
      Positive attitude towards the transplant (13.4%), and Psychological Rejection
      (9.3%), measuring a lack of incorporation of the transplant. These three
      dimensions have a high internal consistency (Cronbach alpha: 0.91, 0.76 and 0.56)
      and are stable over time. Older recipients had more concern about the Donor than
      younger ones. As compared to other medical primary diagnoses, viral hepatitis was
      associated with higher scores on the subscales Positive attitude towards the
      transplant and Psychological Rejection. Interestingly, Psychological rejection
      predicted increased long term risk of death (HR, 1.20; 95% CI, 1.01-1.44, P=.046)
      under multivariate Cox analyses, independently from other variables. CONCLUSION:
      The transplanted organ representations as specifically assessed by the
      Transplanted Organ Questionnaire (TOQ) are relevant in liver transplant
      recipients. Interventions based on the transplant representations after LT should
      be assessed in further studies. Indeed, preventing psychological rejection of the
      transplanted organ and facilitating its psychological incorporation may decrease
      long term mortality after LT.

PMID- 22980541
TI  - Responding to the death of a resident in aged care facilities: perspectives of
      staff and residents.
AB  - A qualitative study using individual semistructured interviews was undertaken to
      explore the perceptions and experiences of 23 aged care residents with mild
      dementia concerning the deaths of coresidents. The views of 25 facility staff
      members were also explored. The study was based in 3 aged residential facilities
      in Victoria, Australia. Interview data indicated that residents and staff had
      differing views. Residents reported that the impact of the death of a coresident
      was much less than staff members thought. Residents generally wanted to be told
      about the death of someone they knew and considered attempts to hide the death
      and the removal of the body both unnecessary and disrespectful. Both groups
      agreed that the celebration of the life of a resident was important, although
      they differed in their preferences for the way this is done. These findings have
      implications for staff education and practice.

PMID- 22980542
TI  - Alveolar bone healing accompanied by severe swelling in cleft children treated
      with bone morphogenetic protein-2 delivered by hydrogel.
AB  - BACKGROUND: The use of osteoinductive growth factors may be preferable for
      alveolar cleft repair because it eliminates the need of bone harvesting. In the
      present prospective randomised pilot study, patients with alveolar clefts were
      treated with either bone morphogenetic protein 2 (BMP-2) delivered by a
      hyaluronan-based hydrogel or autologous bone from the iliac crest. METHODS: Seven
      patients with cleft lip or cleft lip and palate were included. Computed
      tomography (CT) was performed preoperatively and 6 months postoperatively. The
      residual cleft volume was compared with the initial volume. Surgery time,
      bleeding and hospital stay were compared between the two groups. RESULTS: Four
      patients were randomised to treatment with BMP-2. A low BMP-2 concentration of 50
      MUg ml(-1) hydrogel did not induce bone formation in treated patients (n = 2)
      after 6 months, as seen by CT scans. Therefore, the BMP-2 concentration was
      raised to 250 MUg ml(-1) hydrogel in the subsequently randomised patients (n =
      2). Bone formation with volume ratio of 59% and 33% was here verified by CT scans
      after 6 months. However, a severe gingival swelling appeared during the first
      week in patients treated with higher BMP-2 doses. In the autologous bone group (n
      = 3), the volume ratio was 29%, 48%, and 69%. Mean surgery time was 100 min in
      the BMP-2 group and 123 min in the autologous bone group. The mean hospital stay
      was 2.75 and 3.33 days, respectively. CONCLUSIONS: BMP-2 at a concentration of
      250 MUg ml(-1) delivered by a hydrogel can be used to treat alveolar cleft
      defects with good bone quantity and comparable to autologous bone grafts.
      However, severe gingival swelling may limit the use of BMP-2 for these patients.
      Therefore, the study was prematurely closed.

PMID- 22980543
TI  - [Hospitalization: an important opportunity to treat addiction to tobacco smoke].

PMID- 22980544
TI  - [Mini-spirometry: a relevant tool for the screening of COPD in general
      practice?].

PMID- 22980545
TI  - [Epidemiology of tuberculosis in France, outside the metropolitan territory:
      issues and perspectives].

PMID- 22980546
TI  - [Comparative epidemiological study of the tuberculosis - migrant and native
      subjects in Guadeloupe from 2006 to 2011].
AB  - INTRODUCTION: Most of the migrants residing in Guadeloupe are from neighboring
      Caribbean islands, some of which are characterized by a high incidence of
      tuberculosis. The objective of this retrospective and observational study was to
      define the epidemiological characteristics of tuberculosis affecting migrant and
      native populations in Guadeloupe. METHODS: We describe all cases of tuberculosis
      in Guadeloupe identified in these two populations between 1 July 2006 and 30 June
      2011. RESULTS: The incidence of TB among migrants in Guadeloupe was seven times
      higher than that in native subjects in 2010 (33.4 vs. 5.5 new cases/100,000
      inhabitants). Tuberculosis affecting the migrant population was characterized by
      young age of the patients (42 vs. 55 years) and a significant proportion of co
      infection by the human immunodeficiency virus (HIV) (47 vs. 14%, P<0.001). Among
      the patient population studied, the HIV infection increased the risk of
      developing severe tuberculosis (adjusted odds ratio: 2.9; 95%CI: 1.2-6.8).
      Moreover, HIV infection was also a risk factor for death where the infection was
      not controlled (CD4 count <200 units per microliter; adj risk ratio: 3.9; 1.2
      12.4). CONCLUSION: This study shows that the migrant population in Guadeloupe is
      at increased risk of tuberculosis and should be considered as a priority target
      for tuberculosis control program.

PMID- 22980547
TI  - [Management of the sleep apnoea syndrome in a general hospital].
AB  - INTRODUCTION: There are few long-term studies on the management of the sleep
      apnoea syndrome (SAS). PATIENTS AND METHODS: We report a retrospective analysis
      of the management of SAS in the respiratory service of a general hospital between
      1st January 1994 and 1st January 2010. RESULTS: One thousand seven hundred and
      eighteen patients were diagnosed with SAS and treated with continuous positive
      airways pressure (CPAP). One thousand one hundred and seventy-three were still
      being treated on 1st January 2010, representing 68.3% of the total. Four hundred
      and thirty-three had stopped treatment, representing 25.2% of the total number of
      patients treated. Four hundred and fourteen patients had died while being
      treated. The median daily CPAP use among patients still being treated is 6.44
      hours. When CPAP was discontinued 45% occurred in the first 6 months and 91% in
      the first 3 years. The mean apnoea/hypopnoea index of the patients who
      discontinued treatment was 44 as opposed to 51 for those still using CPAP. The
      elderly population adhered well to treatment in the long term. The prevalence of
      severe SAS requiring longer periods of treatment has increased in recent years,
      probably as the result of practical developments. CONCLUSION: The numbers of
      investigations and of patients starting treatment are increasing constantly. Long
      term compliance with CPAP is satisfactory. Discontinuation of treatment occurs
      mainly in the early months and, above all, in the non-compliant group. SAS is
      less severe in those patients who discontinue treatment. Old age is not an
      obstacle to treatment with CPAP.

PMID- 22980548
TI  - [Approach and management of tobacco quitting process of the smoker patient by 149
      residents in a university hospital in Tours].
AB  - INTRODUCTION: How do residents, specialists or general practitioners advise
      patients who are smokers when they are admitted to hospital? Do they assess their
      smoking status? How much do they know about smoking cessation? Do they know the
      tests essential to allow an effective approach to smokers? METHODS: One hundred
      and forty-nine residents were approached over a nine-month period by three
      pharmacy students. The questionnaire addressed the assessment of smokers and the
      possible management of their quitting process: the average time devoted to
      tobacco cessation, knowledge of "brief smoking cessation advice", assessment of
      nicotine addiction and motivation to quit as well as detection of withdrawal
      symptoms, knowledge of the list of nicotine substitutes prescribed by the Tours
      CHRU, and referral of smokers to a smoking cessation specialist. RESULTS: One
      hundred and thirty-four (90%) residents out of the 149 who were questioned
      reported that they tried to assess the smoking status of their patients. The
      average time devoted to tobacco in a consultation was 4 minutes. Seventy-seven
      percent of those concerned knew what constituted "brief smoking cessation" and
      59% reported delivering it regularly. The Fagerstrom test was known by 96% of
      them but only 13% of residents used it. With the exception of two residents in
      pneumonology, the Q. MAT, an assessment test of motivation to quit smoking, was
      unknown to them. Nicotine withdrawal symptoms were well recognised. Sixty-nine
      percent of them knew about the prescription list and 75% of them prescribed
      nicotine substitutes. CONCLUSIONS: The approach to the smoking patient varied
      according to the resident's speciality. Smoking assessment was done
      systematically by most but did not always lead to an assessment of patients'
      motivation to stop smoking or to an offer of assistance with quitting. This
      observation led to the development of a tool to improve the approach to smokers,
      available within the CHRU intranet covering the principles of the management of
      the tobacco quitting process; informing, helping to stop feeling guilty,
      assessing the motivation to quit (Q.MAT), assessing the smoker's addiction
      (Fagerstrom test), offering assistance and a list of nicotine substitutes.

PMID- 22980549
TI  - [Early detection of COPD in primary care: which tools?].
AB  - INTRODUCTION: The early diagnosis of COPD in general practice is not
      satisfactory. OBJECTIVES: To evaluate the impact of different diagnostic tools
      (Piko-6, Software) in general practice (GP). METHODS: A multicentre, randomised,
      controlled study in GP assessing the effect of the tested strategies on the rate
      of referrals for spirometry and the rate of detection of airflow obstruction.
      RESULTS: One thousand one hundred and three patients (55 years old, 60% males, 31
      years of smoking habits) were included by 248 GP. The rates of referal to a
      pneumologist were significantly higher in the Software (50% of patients), and
      Piko/Software (47%) groups than in the Control (22%) and Piko groups (28%). A
      high proportion (44%) of lung function tests recommended by the GP were not
      performed, often because of patient refusal. The confirmation rates were lower in
      the Software and Piko/Software groups (47% and 43%, respectively) compared with
      the Piko and Control groups (68% and 79%, respectively). Concordance between PFT
      and Piko-6 for the diagnosis of airflow obstruction was poor (about 50%).
      CONCLUSIONS: The use of software in association or not with the Piko-6 was useful
      for GPs to identify patients to refer for further lung function testing, but did
      not improve the confirmation of the obstructive syndrome, mainly due to
      reluctance of patients to go on to have further lung function tests. The use of a
      diagnostic tool (software and/or mini-spirometry) does however seem to improve
      early COPD detection.

PMID- 22980550
TI  - [Mature mediastinal teratoma and sarcoid-like granulomatosis].
AB  - INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder. However, when
      epithelioid cell granulomata are found in association with malignancy, they could
      correspond to a sarcoid reaction. CASE REPORT: We report the case of a young
      woman with mediastinal lymphadenopathy containing non-caseating granulomata. She
      also had a mass in the anterior mediastinum which proved, on surgical resection,
      to be an intrathymic mature teratoma. CONCLUSION: An association between a
      sarcoid-like reaction and testicular germ cell tumours has been described in
      literature. Our observation of a sarcoid reaction associated with a teratoma
      could be due to a hypersensitivity reaction to antigen released by the tumour.

PMID- 22980551
TI  - [Isolated tracheobronchial involvement by atrophic polychondritis: role of PET
      scanning].
AB  - INTRODUCTION: Atrophic polychondritis is a rare and serious disease characterised
      by multifocal inflammatory lesions of cartilage. The diagnosis, though urgent, is
      difficult when there is isolated tracheal involvement. CASE REPORT: We report the
      case of a woman of 55 with recent, non-infectious febrile episodes accompanied by
      a steroid sensitive inflammatory syndrome. Auscultation, lung function tests and
      a thoracic CT scan suggested tracheobronchomalacia. Atrophic polychondritis was
      suspected without being confirmed on the basis of histological or biological
      tests; particularly as no other cartilaginous involvement was discovered.
      Laryngeal and tracheal hypermetabolism on a PET scan, performed in the absence of
      corticosteroid treatment, was also in favour of this diagnosis. One month after
      resumption of steroid treatment at increased dosage, this examination was normal.
      Secondarily, after careful reduction of steroids, the patient developed nasal
      chondritis, confirming the diagnosis of atrophic polychondritis. CONCLUSION: The
      PET scanner could be useful in the diagnosis of atrophic polychondritis in its
      isolated tracheobronchial form. Its place in the follow-up of this disease
      remains to be evaluated and should take account of the irradiation dose of this
      examination.

PMID- 22980552
TI  - [Vertebral primary hydatid cyst with mediastinal involvement and paraplegia].
AB  - INTRODUCTION: The vertebrae are the most common localization of hydatid disease
      of bone. This can lead to fatal consequences. CASE REPORT: We report the case of
      a 40-year-old-man, from a rural area, who had symptoms of medullary compression.
      The diagnosis of primary vertebral hydatid cyst, already suspected on the imaging
      data, was confirmed. A right posterolateral thoracotomy allowed drainage of the
      cyst and relief of the medullary compression. Medical treatment with albendazole
      was continued for 4 months. The postoperative course was uneventful and the
      symptoms of medullary compression resolved progressively. No recurrence was
      observed during a follow-up of 24 months. CONCLUSION: Vertebral localization of
      hydatid disease is the most common and serious skeletal complication. Thoracotomy
      allows drainage of the cyst and the pleural cavity, and relieves the medullary
      compression.

PMID- 22980553
TI  - [Anomalous left coronary artery from pulmonary artery revealed by acute
      bronchiolitis].
AB  - Despite its common occurrence bronchiolitis can reveal many disorders such as
      malformations or immunological diseases. We report a rare and serious cause of
      bronchiolitis in the newborn: Anomalous origin of the left coronary artery from
      the pulmonary artery (ALCAPA). CASE REPORT: A four-month-old infant was admitted
      with hypoxic bronchiolitis. Congenital heart disease was suspected in view of the
      severity of symptoms and the association of poor weight gain and cardiomegaly.
      Transthoracic Doppler echocardiography performed by an experienced team and
      coronary multislice spiral computed tomography led to the diagnosis of a left
      coronary artery arising from the proximal left side of the pulmonary artery
      trunk. DISCUSSION: ALCAPA is a rare congenital anomaly that can be revealed by
      intercurrent infection such as bronchiolitis in infancy. Only early diagnosis and
      surgery to restore a system with two normally arising coronary arteries can
      produce a satisfactory outcome, possibly leading to progressive myocardial
      recovery.

PMID- 22980554
TI  - [Cavitating nodules in a 40-year-old non-smoking woman: a very particular
      tumour].
AB  - INTRODUCTION: EML4-ALK fusion gene, is found in 3 to 5 % of lung adenocarcinoma
      and can be targeted by tyrosine-kinase inhibitor (TKI) with impressive
      therapeutic results. CASE REPORT: We report the case of a non-smoking 40-year-old
      woman, diagnosed with metastatic poorly differentiated papillary adenocarcinoma
      of the lung harbouring the ALK fusion gene. After six cycles of first line
      chemotherapy with cisplatine-vinorelbine followed by maintenance treatment with
      erlotinib, the patient achieved a partial response. After disease progression,
      the patient was included in a trial comparing crizotinib with a classic 2nd line
      chemotherapy. After 1 month of crizotinib, the patient's condition improved. CT
      of the chest showed a near-total regression of bilateral pulmonary nodules
      replaced by pulmonary cysts. CONCLUSION: We report in this case a dramatic
      improvement with near-complete vanishing of pulmonary nodules replaced by
      pulmonary cysts in a patient treated with crizotinib. This case reminds us of the
      potential importance of evaluating the molecular diagnosis in lung cancers and
      especially in adenocarcinoma of the lung.

PMID- 22980555
TI  - [Fluffy nodular opacities of the lung after renal transplantation].

PMID- 22980556
TI  - [Master: "biology, physiology, pharmacology of the cardiovascular system and
      respiration", second year, 2010-2011: presentation].

PMID- 22980557
TI  - [Tracheal replacement with cryopreserved aortic allograft: a "hot topic" in
      thoracic surgery].

PMID- 22980558
TI  - [Tracheal replacement with aortic allografts in humans. Experimental prospects].

PMID- 22980559
TI  - Influence of some mineral ions on lipid peroxidation in vitro.
AB  - Recently, a growing interest has been recorded in mineral content of mammalian
      diet, which might impair their development. Focused on the topic, we studied the
      effect of Al3+, Si4+, Sr2+ and Na2S on the intensity of malondialdehyde (MDA)
      production in vitro. MDA, as one of oxidative stress markers, was determined in
      rat brain homogenates in the conditions of lipid peroxidation (LP) activated by
      iron ions and ascorbate. Our results showed a significant increase in lipid
      peroxidation after addition of aluminium ions. We assume a probable impact of
      Al3+ on active or regulatory centres of antioxidant enzymes, resulting in the
      reduction of their antioxidant functions. The addition to Si4+ or Na2S to samples
      with Al3+ significantly decreased Fe2+-activated LP. We can explain the influence
      of Na2S by the formation of insoluble complexes with iron. Similarly, the effect
      of Si4+ can be related to the production of aluminium-silicon complexes. In our
      view, an optimal ratio of aluminium and silicon ions (or aluminium ions and Na2S)
      in the diet might have beneficial effects on brain functions.

PMID- 22980560
TI  - Does prenatal methamphetamine exposure induce cross-sensitization to cocaine and
      morphine in adult male rats?
AB  - The aim of the present study was to examine the cross-sensitization induced by
      prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine.
      Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the
      gestation period. Adult male offspring (prenatally MA- or saline-exposed) were
      divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or
      morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras,
      nociception in Plantar test, and active drug-seeking behavior in conditioned
      place preference (CPP). Our data demonstrate that cocaine increased the
      exploratory activity in Laboras test in prenatally saline-exposed, but decreased
      it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated
      only by the tail withdrawal and it was independent of the prenatal drug exposure.
      CPP test showed that prenatal MA exposure induced rather tolerance than
      sensitization to cocaine. In contrast to cocaine effects, morphine decreased
      rearing activity in both, prenatally MA-exposed and saline-exposed rats, and
      locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar
      test, the results demonstrated that morphine had an analgesic effect in
      prenatally saline-exposed rats but this effect was suppressed in prenatally MA
      exposed rats. In the CPP test morphine induced drug-seeking behavior, which
      however was not affected by prenatal drug exposure. Thus, our data demonstrate
      that there is a cross-effect between prenatal MA exposure and the challenge dose
      of other drug in adulthood, however drug-seeking behavior is not increased by
      prenatal MA exposure as we expected.

PMID- 22980561
TI  - Prevalence of obesity and metabolic syndrome in adult population of selected
      regions of the Czech Republic. Relation to eating habits and smoking.
AB  - Prevalence of the metabolic syndrome is around 25% in Europe but its occurrence
      grows in both genders with increasing age and weight. Lifestyle factors may
      contribute to the risk of developing metabolic syndrome. The objective of this
      study was to determine the relationship between metabolic syndrome and eating
      habits as well as length of sleep and smoking. Participants (519 women and 286
      men aged 18-65 years) were chosen by random selection and questioned about their
      eating habits, sleep length and smoking. This information was combined with
      anthropometric and clinical parameters of metabolic syndrome. The female group
      was divided into two subgroups depending on climacteric stage (before and after
      menopause). Metabolic syndrome prevalence does not differ between regions in
      neither female (29.9%) nor male (32.5%) group. Body mass index >=25 was detected
      in 50.4% of all women and 65.7% of men; 23.5% of all women and 21.7% men had body
      mass index >=30. In conclusion, metabolic syndrome prevalence was proved to
      depend on eating habits and family heredity. Positive correlation between the
      above mentioned factors demonstrated itself in the total sample but not in
      individual regions. Metabolic syndrome prevalence in Czech adults is comparable
      with neighbouring countries. No significant interregional differences in
      metabolic syndrome prevalence within the Czech Republic were detected. In
      conclusion, relationship between eating habits and metabolic syndrome was
      confirmed.

PMID- 22980562
TI  - Association of -607 C/A polymorphism of IL-18 gene (rs1946518) with breast cancer
      risk in Zahedan, Southeast Iran.
AB  - It is known that interleukin-18 (IL-18) is a proinflammatory cytokine with dual
      effects on tumor development and progression. It can increase the immune defense
      against tumor cells. Polymorphisms in the IL-18 genes are known to influence both
      expression levels and may be associated with outcome of cancers. This study was
      aimed to find out the possible association of IL-18 polymorphism at position -607
      C/A (rs1946518) with breast cancer in a sample of Iranian population. We
      investigated IL-18 rs1946518 polymorphism on 72 breast cancer patients and 93
      cancer free women. Genotyping was done using amplification refractory mutation
      system-PCR (ARMS-PCR). We found no significant differences between breast cancer
      patients and control subjects regarding IL-18 rs1946518 polymorphism (chi2=1.78,
      p=0.411). In conclusion, our finding showed that IL-18 rs1946518 polymorphism was
      not associated with breast cancer in a sample of Iranian population.

PMID- 22980563
TI  - Anxiogenic effect of low-dose methamphetamine in the test of elevated plus-maze.
AB  - Methamphetamines (MA) are psychostimulant drugs that are known to change
      individuals' behavior. Psychostimulants could either evoke positive emotions
      (e.g. joy and happiness) or attenuate negative emotional states (e.g. anxiety and
      depression) in humans. In animal experiments, the test of elevated plus-maze
      (EPM) is widely used. This test is appropriate for evaluation of anxiolytic and
      anxiogenic drug effects, or for examination of specific subtypes of anxiety
      disorders. The aim of the present study was to examine the effect of acute single
      dose of MA (1 mg/kg) on the behavior of laboratory rat in the EPM. The detailed
      ethologic analysis of behavior was performed using a modified protocol based on
      the study of Fernandez Espejo (1997). Our results demonstrated that MA affects
      rat's behavior in the EPM in the majority of analyzed categories. The present
      protocol allowed us to determine positive anxiogenic effect of MA.

PMID- 22980564
TI  - Comparison of Helicobacter pylori genotypes obtained from the oropharynx and
      stomach of the same individuals - a pilot study.
AB  - Helicobacter pylori has been recently detected in the oral cavity and oropharynx.
      However, the role it plays in oral and oropharyngeal pathogenesis remains
      unclear. The virulence of H. pylori strains can be distinguished according to the
      virulence factors genes carried. Our research has been focused on realtime PCR
      analysis of cagA and vacA genes of H. pylori strains in tonsils and tonsillar
      squamous cell cancer and their comparison with H. pylori strains obtained from
      the gastric mucosa of the same patients. Urea breath test (UBT) test was used to
      detect a gastric H. pylori infection in 20 patients with previously proven H.
      pylori in the oropharynx. Genotyping of H. pylori in gastric biopsies was
      performed in patients with positive gastric infection. Out of 20 patients
      positive for oropharyngeal H. pylori, 8 were positive for concurrent gastric H.
      pylori infection. In 6 of them gastric biopsies were obtained. Comparison of
      oropharyngeal and stomach H. pylori genotypes showed important differences. Four
      of 6 patients had different H. pylori strains in the oropharynx and stomach. The
      differences were found in cagA gene as well as in vacA gene. The finding of oral
      presence of H. pylori without concurrent stomach infection was confirmed using
      UBT. The results show that more than one H. pylori strain can be present in
      oropharynx and stomach in the same patient. The oropharyngeal infection seems to
      be independent to the gastric infection.

PMID- 22980565
TI  - The diversity of juvenile sarcoidosis symptoms.
AB  - We report a case of juvenile sarcoidosis, emphasizing the variety of clinical
      manifestations. The child had uveitis, which is among the most common
      manifestations of the disease. However, fever of unknown origin,
      glomerulonephritis and lymphadenopathy were also noticed, underscoring the
      diversity of the clinical spectrum of the disease.

PMID- 22980566
TI  - Solitary fibrous tumor of the kidney with massive retroperitoneal recurrence. A
      case presentation.
AB  - Solitary fibrous tumor is an unusual spindle cell neoplasm that usually occurs in
      the pleura but has also been described in other sites. Renal presentation is rare
      and only 38 cases of SFT of the kidney have been described until now. Up to 90%
      of the tumors have benign characteristics. Local retroperitoneal recurrence is
      extremely rare. We report a case of a large malignant solitary fibrous tumor
      recurrence after the surgical excision of the primary tumor. Histological
      examination of the specimen confirmed the diagnosis by revealing highly positive
      reaction of the neoplasmatic cells for vimentin, CD34, bcl-2 and moderately
      positive for actin. The rate of Ki67 lied between 2-7%. No adjuvant therapy was
      given to the patient and he is disease-free with no imaging findings of
      recurrence or metastasis 9 months after the re-operation.

PMID- 22980567
TI  - Embolization of a Biostar device in the pulmonary artery.

PMID- 22980568
TI  - [Primary PCI in ST-elevation myocardial infarction: mode of referral and time to
      PCI].
AB  - INTRODUCTION: According to the current guidelines for treatment of ST-elevation
      myocardial infarction (STEMI), percutaneous coronary intervention (PCI) should be
      performed within 90 min of first medical contact and total ischemic time should
      not exceed 120 min. The aim of this study was to analyze compliance with STEMI
      guidelines in a tertiary PCI center. METHODS: This was a prospective single
      center registry of 223 consecutive STEMI patients referred for primary PCI
      between 2003 and 2007. RESULTS: In this population (mean age 60+/-12 years, 76%
      male), median total ischemic time was 4h 30 min (<120 min in 4% of patients). The
      interval with the best performance was first medical contact to first ECG (median
      8 min, <10 min in 59% of patients). The worst intervals were symptom onset to
      first medical contact (median 104 min, <30 min in 6%) and first ECG to PCI
      (median 140 min, <90 min in 16%). Shorter total ischemic time was associated with
      better post-PCI TIMI flow, TIMI frame count and ST-segment resolution (p<0.03).
      The three most common patient origins were two nearby hospitals (A and B) and the
      pre-hospital emergency system. The pre-hospital group had shorter total ischemic
      time than patients from hospitals A or B (2h 45 min vs. 4h 44 min and 6h 40 min,
      respectively, p<0.05), with shorter door-to-balloon time (89 min vs. 147 min and
      146 min, respectively, p<0.05). CONCLUSIONS: In this population, only a small
      proportion of patients with acute myocardial infarction underwent primary PCI
      within the recommended time. Patients referred through the pre-hospital emergency
      system, although a minority, had the best results in terms of early treatment.
      Compliance with the guidelines translates into better myocardial perfusion
      achieved through primary PCI.

PMID- 22980569
TI  - Renal artery aneurysm: an endovascular treatment for a rare cause of
      hypertension.
AB  - Renal artery aneurysms are a rare cause of secondary hypertension. Endovascular
      treatment with a polytetrafluoroethylene (PTFE)-coated stent can exclude
      aneurysms and treat hypertension. We report the case of a 23-year-old man with
      hypertension diagnosed three years earlier and in whom renal angiography revealed
      three aneurysms involving the right renal artery. A covered stent was implanted,
      resulting in successful exclusion of the aneurysm. Ten months after the procedure
      the patient is asymptomatic and with normal blood pressure without
      antihypertensive therapy.

PMID- 22980570
TI  - Natriuretic peptides in aortic stenosis.
AB  - Aortic stenosis (AS) is the most prevalent valvular heart disease in developed
      countries. Diagnosis, risk stratification and monitoring are usually based on
      clinical and echocardiographic parameters. Complementary methods are needed to
      improve management and outcome, particularly in patients with severe asymptomatic
      AS, whose management remains controversial. Natriuretic peptides (NPs) have
      established value as biomarkers in heart failure, coronary heart disease and
      pulmonary hypertension. This review discusses the usefulness and prognostic value
      of natriuretic peptides in AS. B-type natriuretic peptide (BNP) and its
      prohormone (NT-proBNP) correlate with disease severity, development of symptoms
      and prognosis, but before they can be routinely used in clinical practice,
      additional prospective studies are needed.

PMID- 22980571
TI  - Hypochromia is more prevalent than microcytosis in iron deficiency anaemia.

PMID- 22980572
TI  - Comparison of propidium monoazide-quantitative PCR and reverse transcription
      quantitative PCR for viability detection of fresh Cryptosporidium oocysts
      following disinfection and after long-term storage in water samples.
AB  - Purified oocysts of Cryptosporidium parvum were used to evaluate the
      applicability of two quantitative PCR (qPCR) viability detection methods in raw
      surface water and disinfection treated water. Propidium monoazide-qPCR targeting
      hsp70 gene was compared to reverse transcription (RT)-qPCR heat induced hsp70
      mRNA in water samples spiked with oocysts. Changes in viability of flow cytometry
      sorted fresh and oocysts having undergone various aging periods (up to 48 months
      at 4  degrees C) were evaluated by Ct values obtained from the qPCR before and
      after disinfection scenarios involving ammonia or hydrogen peroxide. Both qPCR
      methods achieved stability in dose dependent responses by hydrogen peroxide
      treatment in distilled water that proved their suitability for the viability
      evaluations. Oocysts exposed to 3% hydrogen peroxide were inactivated at a rate
      of 0.26 h(-1) and 0.93 h(-1), as measured by the mRNA assay and the PMA-DNA
      assay, respectively. In contrast, the PMA-DNA assay was not as sensitive as the
      mRNA assay in detecting viability alterations followed by exposure to ammonia or
      after a long-term storage in 4  degrees C in distilled water since no dose
      response dependency was achieved. Surface water concentrates containing enhanced
      suspendable solids determined that changes in viability were frequently detected
      only by the mRNA method. Failure of, or inconsistency in the detection of oocysts
      viability with the PMA-DNA method, apparently resulted from solids that might
      have reduced light penetration through the samples, and thus inhibited the cross
      linking step of PMA-DNA assay.

PMID- 22980573
TI  - Effect of diffusive transport limitations on UO2 dissolution.
AB  - The effects of diffusive transport limitations on the dissolution of UO(2) were
      investigated using an artificial groundwater prepared to simulate the conditions
      at the Old Rifle aquifer site in Colorado, USA. Controlled batch, continuously
      stirred tank (CSTR), and plug flow reactors were used to study UO(2) dissolution
      in the absence and presence of diffusive limitations exerted by permeable sample
      cells. The net rate of uranium release following oxidative UO(2) dissolution
      obtained from diffusion-limited batch experiments was ten times lower than that
      obtained for UO(2) dissolution with no permeable sample cells. The release rate
      of uranium to bulk solution from UO(2) contained in permeable sample cells under
      advective flow conditions was more than 100 times lower than that obtained from
      CSTR experiments without diffusive limitations. A 1-dimensional transport model
      was developed that could successfully simulate diffusion-limited release of U
      following oxidative UO(2) dissolution with the dominant rate-limiting process
      being the transport of U(VI) out of the cells. Scanning electron microscopy, X
      ray diffraction, and extended X-ray absorption fine structure spectroscopy
      (EXAFS) characterization of the UO(2) solids recovered from batch experiments
      suggest that oxidative dissolution was more evident in the absence of diffusive
      limitations. Ca-EXAFS spectra indicate the presence of Ca in the reacted UO(2)
      solids with a coordination environment similar to that of a Ca-O-Si mineral. The
      findings from this study advance our overall understanding of the coupling of
      geochemical and transport processes that can lead to differences in dissolution
      rates measured in the field and in laboratory experiments.

PMID- 22980574
TI  - Selective removal of nitrate ion using a novel composite carbon electrode in
      capacitive deionization.
AB  - We fabricated nitrate-selective composite carbon electrodes (NSCCEs) for use in
      capacitive deionization to remove nitrate ions selectively from a solution
      containing a mixture of anions. The NSCCE was fabricated by coating the surface
      of a carbon electrode with the anion exchange resin, BHP55, after grinding the
      resin into fine powder. BHP55 is known to be selective for nitrate ions. We
      performed desalination experiments on a solution containing 5.0 mM NaCl and 2.0
      mM NaNO(3) using the NSCCE system constructed with the fabricated electrode. The
      selective removal of nitrate in the NSCCE system was compared to a membrane
      capacitive deionization (MCDI) system constructed with ion exchange membranes and
      carbon electrodes. The total quantity of chloride and nitrate ions adsorbed onto
      the unit area of the electrode in the MCDI system was 25 mmol/m(2) at a cell
      potential of 1.0 V. The adsorption of nitrate ions was 8.3 mmol/m(2), accounting
      for 33% of the total. In contrast, the total anion adsorption in the NSCCE system
      was 34 mmol/m(2), 36% greater than the total anion adsorption of the MCDI system.
      The adsorption of nitrate ions was 19 mmol/m(2), 2.3-times greater than the
      adsorption in the MCDI system. These results showed that the ions were initially
      adsorbed by an electrostatic force, and the ion exchange reactions then occurred
      between the resin powder in the coated layer and the solution containing mixed
      anions.

PMID- 22980575
TI  - Evaluation of shear stress accumulation on blood components in normal and
      dysfunctional bileaflet mechanical heart valves using smoothed particle
      hydrodynamics.
AB  - Evaluating shear induced hemodynamic complications is one of the major concerns
      in design of the mechanical heart valves (MHVs). The monitoring of these events
      relies on both numerical simulations and experimental measurements. Currently,
      numerical approaches are mainly based on a combined Eulerian-Lagrangian approach.
      A more straightforward evaluation can be based on the Lagrangian analysis of the
      whole blood. As a consequence, Lagrangian meshfree methods are more adapted to
      such evaluation. In this study, smoothed particle hydrodynamics (SPH), a fully
      meshfree particle method originated to simulate compressible astrophysical flows,
      is applied to study the flow through a normal and a dysfunctional bileaflet
      mechanical heart valves (BMHVs). The SPH results are compared with the reference
      data. The accumulation of shear stress patterns on blood components illustrates
      the important role played by non-physiological flow patterns and mainly vortical
      structures in this issue. The statistical distribution of particles with respect
      to shear stress loading history provides important information regarding the
      relative number of blood components that can be damaged. This can be used as a
      measure of the response of blood components to the presence of the valve implant
      or any implantable medical device. This work presents the first attempt to
      simulate pulsatile flow through BMHVs using SPH method.

PMID- 22980576
TI  - Effects of ankle foot orthosis in stiff knee gait in adults with hemiplegia.
AB  - Stroke survivors present a less efficient gait compared to healthy subjects due
      to abnormal knee flexion during the swing phase of gait, associated with
      spasticity of the rectus femoris muscle and overactivity of the ankle
      plantarflexors. It is relevant to understand the effect of the ankle foot
      orthosis (AFO) on gait in individuals with plantarflexor spasticity. The aim of
      this study was to compare the knee kinematics with an AFO/footwear combination
      and barefoot in post-stroke subjects with plantarflexor spasticity. Ten subjects
      with chronic hemiplegia were measured. Two kinematic variables were assessed
      during the swing phase of the paretic limb: knee flexion angle at toeoff and peak
      knee flexion angle. We also analyzed gait speed and step length of the non
      paretic limb. All variables were obtained with and without the orthosis.
      Kinematic data were acquired using a motion capture system (ELITE). Subjects
      wearing an AFO showed significant improvements in gait speed (0.62 m/s (0.08 SD)
      vs. 0.47 m/s (0.13 SD) (p=0.007)), step length of the non-paretic limb (42 cm
      (5.9 SD) vs. 33.5 cm (6.6 SD) (p=0.005)) and peak knee flexion angle during the
      swing phase: 30.7 degrees  (14.1 degrees  SD) vs. 26.3 degrees  (11.7 degrees 
      SD) p=0.005. No significant differences were obtained in the knee flexion angle
      at toeoff between no AFO and AFO conditions. We described benefits with
      AFO/footwear use in the kinematics of the knee, the step length of the non
      paretic limb, and the gait velocity in hemiplegic subjects after mild to moderate
      stroke. We conclude that the use of an AFO can improve the gait pattern and
      increase velocity in these subjects.

PMID- 22980577
TI  - Effects of pressure on arterial failure.
AB  - A three-dimensional multilayer model of mechanical response for analyzing the
      effect of pressure on arterial failure is presented in this work. The multilayer
      arterial wall is considered to be composed of five different layers. The three
      dimensional effects are incorporated within the five-concentric axisymmetric
      layers while incorporating the nonlinear elastic characteristics under combined
      extension and inflation. Constitutive equations for fiber-reinforced material are
      employed for three of the major layers, i.e., intima, media and adventitia and an
      isotropic material model is employed for the other two layers, i.e., endothelium
      and internal elastic lamina. Our own developed three-dimensional five-layer model
      has been utilized to model propagated rupture area of the arterial wall. Required
      parameters for each layer are obtained by using a nonlinear least square method
      fitted to in vivo non-invasive experimental data of human artery and the effects
      of pressure on arterial failure are examined. The solutions from our
      computational model are compared with previous studies and good agreements are
      observed. Local stresses and strain distributions across the deformed arterial
      wall are illustrated and consequently the rupture area is predicted by varying
      luminal pressure in the physiological range and beyond. The effects of pressure
      on the arterial failure have been interpreted based on this comprehensive three
      dimensional five-layer arterial wall model. This is the first study which employs
      two constitutive equations and incorporates a five-layer arterial wall model in
      three-dimensions based on in vivo non-invasive experimental data for a human
      artery.

PMID- 22980580
TI  - mRNA expression and promoter DNA methylation status of CDKi p21 and p57 genes in
      ex vivo expanded CD34 (+) cells following co-culture with mesenchymal stromal
      cells and growth factors.
AB  - BACKGROUND: Several studies indicate that ex vivo cytokine-based expansion of
      cord blood (CB) CD34(+) cells can induce cell cycle abnormality in expanded
      cells. Cycline-dependent kinase inhibitors, p21 and p57, are critical regulators
      of cell cycle. We investigated  mRNA expression and promoter DNA methylation
      status of p21 and p57 genes in ex vivo expanded CD34(+) cells in different
      culture conditions. MATERIALS AND METHODS: Human CB CD34(+) cells were cultured
      either in cytokine-supplemented liquid culture  or in co-culture with mesenchymal
      stromal cells (co-culture system) in presence and absence of cytokine. After 14
      days, expansion fold in total nucleated cells (TNCs), CD34(+) cells,
      CD34(+)/CD38(-) cells and colony-forming units in culture (CFU-C) count was 
      determined. Moreover, mRNA expression level and promoter DNA methylation status
      of p21 and p57 genes in expanded CD34(+) cells were analyzed by real-time reverse
      transcriptase-polymerase chain reaction (PCR) and methylation-specific PCR
      technique, respectively. RESULTS: Maximum expansion of TNC, CD34(+) cells,
      CD34(+)/CD38(-) cells and CFU-C was seen at day 10 in all three culture
      conditions. p21 and p57 mRNA expression level decreased in both cytokine liquid
      culture and co-culture system with cytokine, while in the co-culture  system
      without cytokine, the mRNA expression of p21 and p57 genes relatively increased.
      In addition, promoter DNA methylation status of p21 and p57 genes did not change
      during expansion in all three culture conditions. CONCLUSIONS: Co-culture of CB
      CD34(+) cells  with mesenchymal stromal cells, especially in the absence of
      cytokines, maintained mRNA expression of p21 and p57 genes in ex vivo expanded
      CD34(+) cells. Moreover, transcriptional repression of p21 and p57 genes in ex
      vivo expanded CD34(+) cells was not mediated  by promoter DNA methylation.

PMID- 22980581
TI  - Chromium, nickel and vanadium mobility in soils derived from fluvioglacial sands.
AB  - The presented study was focused on soils developed from fluvioglacial sands from
      the Puszcza Borecka forest complex. The mobility of chromium, nickel and vanadium
      was evaluated with regard to litho- and pedogenic factors. The aim of the study
      was to determine with which soil constituents fractions of heavy metals are bound
      with particular attention drawn on the mobile fractions (F1+F2). Heavy metal
      fractions in the soils were determined using the sequential extraction method of
      Tessier et al. The purpose of sequential extraction methods to soil samples
      provides relevant information about possible toxicity when they are discharged
      into the soil environment. Chromium, nickel, and vanadium occurred predominantly
      in the fraction bound with iron and manganese oxides and in the residual
      fraction, thus showed low mobility. With regard to mobility, the elements studied
      can be arranged as follows: V<Cr<Ni. The content of the mobile fractions depended
      on the soil texture. The influence of the rusting process on the distribution of
      the bioavailable fractions was observed in the soil profiles.

PMID- 22980582
TI  - Pyrite-enhanced methylene blue degradation in non-thermal plasma water treatment
      reactor.
AB  - In this study, methylene blue (MB) removal from an aqueous phase by electrical
      discharge non-thermal plasma (NTP) over water was investigated using three
      different feed gases: N(2), Ar, and O(2). The results showed that the dye removal
      rate was not strongly dependent on the feed gas when the electrical current was
      kept the same for all gases. The hydrogen peroxide generation in the water varied
      according to the feed gas (N(2)<Ar<O(2)). Using O(2) as the feed gas, pyrite was
      added to the reactor in acid medium resulting in an accentuated increase in the
      dye removal, which suggests that pyrite acts as a Fenton-like catalyst. The total
      organic carbon (TOC) content of the dye solution decreased slightly as the plasma
      treatment time increased, but in the presence of the pyrite catalyst the TOC
      removal increased substantially. The acute toxicity test using Artemia sp.
      microcrustaceans showed that the treated solution is not toxic when Ar, O(2) or
      O(2)-pyrite is employed. Electrospray ionization mass spectrometry analysis (ESI
      MS) of the treated samples indicated that the dye degradation occurs via high
      energy electron impact as well as successive hydroxylation in the benzene rings
      of the dye molecules.

PMID- 22980583
TI  - Molecular characterization of the first fluoroquinolone resistant strains of
      Streptococcus agalactiae isolated in Brazil.
AB  - Three isolates of Streptococcus agalactiae, recovered from residents of the
      metropolitan area of Rio de Janeiro with significant bacteriuria, were found to
      be resistant to levofloxacin. Determination of the minimal inhibitory
      concentration (MIC) confirmed one isolate as intermediate and two as resistant to
      levofloxacin. No reduction in levofloxacin MIC was observed with reserpine,
      indicating that resistance was not caused by an efflux mechanism. Typical point
      mutations were observed in the quinolone resistance determinant region of gyrA
      and parC. Other point mutations in parC generated novel altered codons: Ser80
      >Pro in the intermediate resistance isolate, and Gly128->Asp in a resistant
      isolate. Through molecular modeling, it was possible to observe that these novel
      substitutions might not play a role in resistance, since these amino acids were
      not involved in the antibiotic binding site. Pulsed field gel electrophoresis
      profiles revealed a non-clonal trend among these isolates. This is the first
      report of genetic characterization of levofloxacin-resistant S. agalactiae
      strains in Brazil.

PMID- 22980584
TI  - Risk factors for KPC-producing Klebsiella pneumoniae bacteremia.
AB  - The molecular epidemiology of carbapenemase-producing Klebsiella pneumoniae (KPC)
      has been largely investigated, but limited clinical information is available. A
      case-control study was performed to evaluate the risk factors for KPC bacteremia
      in hospitalized patients. Cases were patients with KPC bacteremia and controls
      were patients with non-KPC bacteremia. A total of 85 patients were included, 18
      (21.2%) were KPC, and 67 (78.8%) were non-KPC (40 [59.7%] of them were extended
      spectrum beta-lactamase producers). All KPC isolates were type 2 producers. These
      isolates belong to five distinct clones. Multivariate analysis showed that age
      (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02 - 1.11; p = 0.004),
      presence of mechanical ventilation (OR, 11.1; 95% CI, 1.92 - 63.3; p = 0.007) and
      fluoroquinolone exposure during hospitalization (OR, 28.9; 95% CI, 1.85 - 454.6;
      p = 0.02) were independent risk factors for KPC in patients with K. pneumoniae
      bacteremia. Factors associated with severity of illness, such as age and
      mechanical ventilation, seem to be the main risks factors for KPC.
      Fluoroquinolones use might be a risk factor for KPC bacteremia. Further
      investigations on risk factors for KPC are warranted.

PMID- 22980585
TI  - Evaluation of in-house mpt64 real-time PCR for rapid detection of Mycobacterium
      tuberculosis in pulmonary and extra-pulmonary specimens.

PMID- 22980586
TI  - Knowledge of the patients regarding leprosy and adherence to treatment.
AB  - Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is
      known for its great disfiguring capacity and is considered an extremely serious
      disease to public health worldwide. The state of Ceara ranks 13th in number of
      cases of leprosy in Brazil, and fourth in Northeastern region, with an average of
      2,149 new cases diagnosed every year. This study aimed to evaluate the knowledge
      of leprosy patients regarding treatment, and to assess the level of treatment
      adherence and its possible barriers. The study was conducted in the reference
      center for dermatology, from September 2010 to October 2010, in Fortaleza, Ceara.
      The study data were collected by means of a structured interview, along with the
      Morisky-Green test, in order to assess treatment adherence and barriers to
      adherence. A total of 70 patients were interviewed, out of whom 66 were new
      cases. The majority of patients were between 42 and 50 years old, and 37 (52.9%)
      were male. Most patients were clinically classified as presenting multibacillary
      leprosy (80%), and 78.6% of them were from Fortaleza, Brazil. The Morisky-Green
      test indicated that 62.9% of patients presented a low level of adherence
      (p<0.005), despite claiming to aware of the disease risks. However, it was
      observed that 57.1% of the patients had no difficulty adhering to treatment,
      while 38.6% reported little difficulty. This study shows that despite the
      patients claiming to be familiar with leprosy and its treatment, the Morisky
      Green test clearly demonstrated that they actually were not aware of the
      principles of therapy, which is evidenced by the low degree of treatment
      adherence.

PMID- 22980588
TI  - Physiological functions of the effects of the different bathing method on
      recovery from local muscle fatigue.
AB  - BACKGROUND: Recently, mist saunas have been used in the home as a new bathing
      style in Japan. However, there are still few reports on the effects of bathing
      methods on recovery from muscle fatigue. Furthermore, the effect of mist sauna
      bathing on human physiological function has not yet been revealed. Therefore, we
      measured the physiological effects of bathing methods including the mist sauna on
      recovery from muscle fatigue. METHODS: The bathing methods studied included four
      conditions: full immersion bath, shower, mist sauna, and no bathing as a control.
      Ten men participated in this study. The participants completed four consecutive
      sessions: a 30-min rest period, a 10-min all out elbow flexion task period, a 10
      min bathing period, and a 10-min recovery period. We evaluated the mean power
      frequency (MNF) of the electromyogram (EMG), rectal temperature (Tre), skin
      temperature (Tsk), skin blood flow (SBF), concentration of oxygenated hemoglobin
      (O2Hb), and subjective evaluation. RESULTS: We found that the MNF under the full
      immersion bath condition was significantly higher than those under the other
      conditions. Furthermore, Tre, SBF, and O2Hb under the full immersion bath
      condition were significantly higher than under the other conditions. CONCLUSIONS:
      Following the results for the full immersion bath condition, the SBF and O2Hb of
      the mist sauna condition were significantly higher than those for the shower and
      no bathing conditions. These results suggest that full immersion bath and mist
      sauna are effective in facilitating recovery from muscle fatigue.

PMID- 22980587
TI  - Global prefrontal and fronto-amygdala dysconnectivity in bipolar I disorder with
      psychosis history.
AB  - BACKGROUND: Pathophysiological models of bipolar disorder postulate that mood
      dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal
      cortex (PFC) inhibitory control. This might occur due to both disruptions within
      PFC networks and abnormal inhibition over subcortical structures involved in
      emotional processing. However, no study has examined global PFC dysconnectivity
      in bipolar disorder and tested whether regions with within-PFC dysconnectivity
      also exhibit fronto-limbic connectivity deficits. Furthermore, no study has
      investigated whether such connectivity disruptions differ for bipolar patients
      with psychosis history, who might exhibit a more severe clinical course. METHODS:
      We collected resting-state functional magnetic resonance imaging at 3T in 68
      remitted bipolar I patients (34 with psychosis history) and 51 demographically
      matched healthy participants. We employed a recently developed global brain
      connectivity method, restricted to PFC (rGBC). We also independently tested
      connectivity between anatomically defined amygdala and PFC. RESULTS: Bipolar
      patients exhibited reduced medial prefrontal cortex (mPFC) rGBC, increased
      amygdala-mPFC connectivity, and reduced connectivity between amygdala and
      dorsolateral PFC. All effects were driven by psychosis history. Moreover, the
      magnitude of observed effects was significantly associated with lifetime
      psychotic symptom severity. CONCLUSIONS: This convergence between rGBC, seed
      based amygdala findings, and symptom severity analyses highlights that mPFC, a
      core emotion regulation region, exhibits both within-PFC dysconnectivity and
      connectivity abnormalities with limbic structures in bipolar illness.
      Furthermore, lateral PFC dysconnectivity in patients with psychosis history
      converges with published work in schizophrenia, indicating possible shared risk
      factors. Observed dysconnectivity in remitted patients suggests a bipolar trait
      characteristic and might constitute a risk factor for phasic features of the
      disorder.

PMID- 22980589
TI  - Entecavir treatment of children 2-16 years of age with chronic hepatitis B
      infection.
AB  - BACKGROUND AND STUDY AIMS: Childhood acquired chronic hepatitis B is associated
      with a significant lifetime risk of developing cirrhosis or hepatocellular
      carcinoma. Our objective in this study was to report retrospectively the response
      to treatment with Entecavir in 8 children with chronic hepatitis B followed at
      the King Abdulaziz University Hospital, Jeddah, Saudi Arabia. PATIENTS AND
      METHODS: This study is an observational hospital based chart review of children
      and adolescents with chronic hepatitis B treated with entecavir at the King
      Abdulaziz University Hospital, Jeddah, Saudi Arabia in the period between June
      2007 and July 2011. RESULTS: Half of the studied group was males, and the median
      age at the time of treatment was 4.8 years (range, 2.6-15). All subjects
      displayed infection with HBV genotype D and all were HBeAg positive. Half of the
      patients had been previously treated with lamivudine, while the remaining half
      was treatment naive patients. The mean ALT+/-SD was 84.9+/-34.7IU/L (range, 46
      133) and the mean HBV DNA was 5.01*10(8)+/-5.7*10(8) IU/mL (range, 5.5*10(7)
      1.3*10(9)). Patients were treated with a daily oral dose of 0.5mg entecavir, and
      the mean duration of treatment was 23.8+/-11.9 months, (range 14.9-44.7 months).
      HBV DNA suppression of more than 2 log(10) was achieved in all patients. HBV DNA
      was undetected in 37.5%, with ALT normalization in 87.5% and lastly HBeAg
      seroconversion and loss occurred in 37.5%. No adverse side effects were observed
      during the treatment with entecavir. CONCLUSION: We conclude from this limited
      data that 37.5% of children treated with entecavir achieved HBeAg loss and
      seroconversion with no side effects observed during treatment period, however
      long term safety and efficacy in children should be demonstrated through a
      multicenter study, enrolling large number of patients.

PMID- 22980590
TI  - Predictive accuracy of serum hyaluronic acid as a non-invasive marker of fibrosis
      in a cohort of multi-transfused Egyptian children with beta-thalassaemia major.
AB  - BACKGROUND AND STUDY AIM: Liver disease remains a major cause of morbidity and
      mortality in patients with beta-thalassaemia major (beta-TM); therefore, its
      identification at an early stage is of great significance. Serum hyaluronic acid
      (HA) is considered as a non-invasive marker that appears early before
      pathological changes occur. We aim to determine the predictive accuracy of HA in
      detecting and staging hepatic fibrosis in beta-TM patients. PATIENTS AND METHODS:
      30 Egyptian children with beta-TM, and 15 age and sex-matched controls were
      studied. All had abdominal ultrasonography (US), measurement of serum amino
      transferases (ALT, AST); hepatitis C, B and human immunodeficiency viruses (HCV,
      HBV, HIV) sero-markers, serum ferritin and HA. Liver biopsy was done for patients
      and fibrosis was scaled using Metavir scoring system and liver iron concentration
      (LIC) was measured. RESULTS: Twenty patients (67.7%) had sero-markers of HCV,
      none had HBV or HIV. Serum HA was significantly higher in patients (90.78+/-28.79
      ng/ml) compared to controls (21.1+/-13.24 ng/ml) with p<0.05. No difference
      between HCV infected and non-infected patients was detected. Positive significant
      correlation was detected between serum HA and stages of fibrosis by
      histopathology and US. No correlation was found between serum HA and age, sex,
      weight, height, haemoglobin level, platelet count, AST, serum ferritin, necro
      inflammatory grade, and LIC. CONCLUSIONS: Serum HA is a valuable non-invasive
      marker that may contribute to the assessment of liver fibrosis in multi
      transfused children and adolescents with beta-TM, irrespective of concomitant HCV
      infection.

PMID- 22980591
TI  - Clinical significance of elevated alpha-foetoprotein (AFP) in patients with
      chronic hepatitis C without hepatocellular carcinoma in upper EGYPT.
AB  - BACKGROUND AND STUDY AIMS: Egypt has the highest prevalence of hepatitis C in the
      world. Alpha-foetoprotein (AFP) is important in the diagnosis of hepatocellular
      carcinoma (HCC), but elevated AFP levels have also been observed in chronic
      hepatitis C (CHC) without HCC. We evaluated the clinical correlation between
      elevated AFP levels and CHC. We analysed data from a population-based cohort of
      patients with hepatitis C virus (HCV) infection to assess the prevalence of
      elevated serum AFP, to determine its association with clinical and virologic
      parameters and with clinical outcomes. PATIENTS AND METHODS: From December 2009
      to April 2011, 121 patients with no evidence of HCC with regular abdominal
      ultrasound or other imaging studies (multislice computed tomography (MSCT) or
      magnetic resonance imaging (MRI)) were controlled by a chart review. RESULTS: The
      prevalence of elevated AFP >=10ngml(-1) was 11.6%. Univariate analysis revealed
      that fibrosis stage III/IV, alanine aminotransferase (ALT) more than 45IUl(-1)
      and platelet count less than 150*10(9) l(-1) were significantly associated with
      elevated AFP. Multivariate analysis revealed that the independent variable
      associated with elevated serum AFP was fibrosis stage III/IV, p=0.015.
      Multivariate analysis also revealed that AST>45IUl(-1) and AFP >=10 ngml(-1) were
      associated with advanced fibrosis using a cut-off AFP value >10 ngml(-1). The
      sensitivity and specificity of diagnosing fibrosis score III/IV were 26.1% and
      97.3%, respectively. CONCLUSIONS: Elevated AFP levels were observed in 11.65% of
      patients with CHC. Elevated AFP levels correlated positively with fibrosis stage
      III/IV; ALT elevation, thrombocytopenia and AFP >=10 ngml(-1) were associated
      with advanced fibrosis.

PMID- 22980592
TI  - Serum leptin level and its association with fatigue in patients with chronic
      hepatitis C virus infection.
AB  - BACKGROUND AND STUDY AIM: Fatigue is one of the most common presenting symptoms
      of chronic hepatitis C virus (HCV) infection. Its pathogenesis has been poorly
      investigated. Serum leptin levels are increased in cirrhosis and are suggested to
      have a role in the mediation of fatigue. This study was designed to assess
      possible association of serum leptin levels with fatigue and severity of liver
      disease in Egyptian patients with chronic hepatitis C infection. PATIENTS AND
      METHODS: Seventy patients and 20 control subjects participated in the study. They
      were subjected to clinical and laboratory assessment, the determination of serum
      leptin level by ELISA and the assessment of fatigue using the multidimensional
      assessment of fatigue (MAF) scale. Respondents are asked to reflect on fatigue
      patterns for the past week. The MAF is a revision of the Piper Fatigue Scale.
      RESULTS: Fatigue was present in all patients (100%) and 13 subjects of the
      control group (65%). There was a highly significant statistical difference
      between cases and controls regarding the presence and severity of fatigue. Serum
      leptin level was significantly higher in cases (24.9+/-28) in comparison to the
      control subjects (14.8+/-8). Serum leptin was not related to severity of liver
      disease as assessed by the Child Pugh classification. Serum leptin levels were
      directly correlated to the severity of fatigue (p<0.01) in patients but not in
      the control subjects. CONCLUSION: Fatigue is highly prevalent in Egyptian
      patients with chronic HCV infection. Leptin might play a role in the mediation of
      fatigue in those patients drawing attention to biological basis of one of the
      most common symptoms facing clinician dealing with this problem.

PMID- 22980593
TI  - Correlation between HCV viraemia and splenic volume in chronic HCV infected
      patients: an Egyptian study.
AB  - BACKGROUND AND STUDY AIMS: As HCV lymphotropism was ascertained, this study was
      carried out to verify the possible involvement of the spleen in HCV-related
      chronic hepatitis. PATIENTS AND METHODS: A cross-sectional study was conducted on
      97 HCV infected patients attending for treatment with interferon, categorised as
      follows; before treatment (group I, n=49), non-responders (group II, n=18),
      responders (group III, n=18) and group IV (n=12) including patients with HCV RNA
      below detection limit after 24 weeks of treatment. A control group of healthy
      blood donors (n=19) was enrolled in our study. Conventional ultrasonography was
      carried out on all participants. Splenic volume was measured and compared between
      the groups, and its relationship to HCV RNA concentration was investigated.
      RESULTS: It was found that the splenic volume of patients of both groups I and II
      is significantly greater than that of the control group (p-values : 0.004 and
      0.009, respectively) and, of patients of both groups III and IV. The latter are
      not significantly greater than that of the control group (p-value: 0.8 and 0.6,
      respectively). A significant positive relationship was detected between the
      splenic volume and the HCV RNA concentration in group I (r=0.56, p-value=0.00)
      but this is insignificant in group II. There is no significant relationship
      between the splenic longitudinal diameter and the HCV RNA concentration in any of
      the studied groups. CONCLUSION: The splenic volume positively correlated with HCV
      RNA concentration in HCV positive patients, but this become insignificant in non
      responders to interferon therapy. The successful response to interferon therapy
      matches with near normal splenic volume whilst non-responders to Interferon
      therapy matches with increased splenic volume. The change in the viral load leads
      to a corresponding change in the splenic volume and does not affect the splenic
      longitudinal diameter.

PMID- 22980594
TI  - Evaluation of different therapeutic approaches for spontaneous bacterial
      peritonitis.
AB  - BACKGROUND AND STUDY AIMS: Spontaneous bacterial peritonitis (SBP) is a
      significant cause of mortality in cirrhosis. Reducing toxic burden of infected
      ascitic fluid through paracentesis needs further studies as adjunctive therapy of
      SBP. We aimed to evaluate different therapies for SBP. PATIENTS AND METHODS:
      Thirty-six cirrhotic ascitic patients with SBP were examined and classified
      according to treatment modality (5-7 days) into: Group A received cefotaxime,
      group B received cefotaxime and albumin 1.5 g/kg body weight within 6h of SBP
      being diagnosed and 1g/kg body weight on day 3, group C received cefotaxime and
      paracentesis with volume dependent albumin infusion. Control group of 12
      cirrhotic ascitic patients free from SBP were included. Routine laboratory tests,
      ascitic fluid analysis for leucocytes and culture were done, inflammatory
      mediators such as nitric oxide and tumour necrosis factor alpha were measured in
      serum and ascitic fluid. Duplex-Doppler assessment of portal flow volume and
      renal resistive index, Echocardiography to measure end diastolic and end systolic
      volumes, stroke volume and cardiac output were done. Tests were carried out
      before and after therapy. RESULTS: Treatment response was assessed by, cardiac
      haemodynamics, portal and renal flow and NO and TNF. All studied parameters;
      laboratory, cardiac, Doppler exhibited a significant improvement in group B in
      contrast to the other groups as demonstrated by post therapy reduction of (blood
      and ascitic fluid WBCs & PNLS, serum and ascitic NO & TNF and renal resistive
      index), elevation of (serum albumin and portal flow volume) and improvement of
      cardiac haemodynamic. CONCLUSION: Treatment of spontaneous bacterial peritonitis
      by cefotaxime and body weight based albumin infusion gave most favourable results
      compared to other regimens. Postulation of removing toxic burden through
      paracentesis has not been confirmed.

PMID- 22980595
TI  - Hepatobiliary disorders among naive patients with ulcerative colitis in Upper
      Egypt.
AB  - BACKGROUND AND STUDY AIMS: Association of ulcerative colitis (UC) with
      hepatobiliary disorders is well recognised. The most common hepatobiliary
      complications of inflammatory bowel disease (IBD) are fatty liver infiltration
      and cholelithiasis. The prevalence of liver dysfunction in IBD remains unclear.
      The aim of the study is to try to identify the frequency and risk factors of
      hepatobiliary disorders among patients with UC in Upper Egypt. PATIENTS AND
      METHODS: We prospectively analysed 33 patients with newly diagnosed UC of
      Tropical Medicine and Gastroenterology Department, Assiut University Hospital.
      For all participants, the following were conducted: clinical evaluation,
      abdominal ultrasonography (US) examination and laboratory investigations. Risk
      factors of hepatobiliary disorders were identified using univariate, then
      multivariate analysis. RESULTS: The frequency of hepatic disorders (fatty liver
      and elevated liver chemistry) was 75.8% in study patients while the frequency of
      biliary disorders (gallbladder stones and gallbladder wall thickening) was 54.5%.
      A higher risk of hepatic disorders was observed with older age (odds ratio (OR)
      14, 95% confidence interval (CI) 2-124). A higher risk of biliary disorders was
      observed with UC severe activity index (OR 27, 95% CI 3-292). CONCLUSIONS: The
      frequency of hepatobiliary disorders in patients with UC exceeded what was
      previously reported. High frequency of hepatic disorders was related to older
      age, while that of biliary disorders was related to UC activity.

PMID- 22980596
TI  - A prospective randomised comparative study of endoscopic band ligation versus
      injection sclerotherapy of bleeding internal haemorrhoids in patients with liver
      cirrhosis.
AB  - BACKGROUND AND STUDY AIMS: Bleeding internal haemorrhoids are common and used to
      be treated surgically with too many complications. Endoscopic therapy is trying
      to take the lead. Sclerotherapy and rubber band ligation are the candidates to
      replace surgical therapy especially in patients with liver cirrhosis. The aim of
      this study was to compare endoscopic injection sclerotherapy (EIS) to endoscopic
      rubber band ligation (EBL) regarding effectiveness and complications in the
      treatment of bleeding internal haemorrhoids in Egyptian patients with liver
      cirrhosis. PATIENTS AND METHODS: One hundred and twenty adult patients with liver
      cirrhosis and bleeding internal haemorrhoids were randomised into two equal
      groups; the first treated with EBL using Saeed multiband ligator, and the second
      with EIS using either ethanolamine oleate 5% or N-butyl cyanoacrylate. All groups
      were matched as regards age, sex, Child score and pre-procedure Doppler values.
      Patients were followed up clinically and with abdominal ultrasound/Doppler for 6
      months. Endoscopic and endosonography/Doppler was done before and one month after
      the procedure. Pre and post-procedure data were recorded and analysed. RESULTS:
      Both techniques were highly effective in the control of bleeding from internal
      haemorrhoids with a low rebleeding [10% in the EBL group and 13.33% in the EIS
      group] and recurrence [20% in the EBL group 20% in the EIS group] rates. Child
      score had a positive correlation with rebleeding and recurrence in EIS group
      only. Pain score and need for analgesia were significantly higher while patient
      satisfaction was significantly lower in EIS compared to EBL [p<0.05]. No
      significant difference between ethanolamine and cyanoacrylate subgroups was found
      [p>0.05]. CONCLUSIONS: Both EBL and EIS were effective in the treatment of
      bleeding internal haemorrhoids in patients with liver cirrhosis. EBL had
      significantly less pain and higher patient satisfaction than EIS. EBL was also
      safer in patients with advanced cirrhosis.

PMID- 22980597
TI  - Increased oesophageal cancer mortality rate in Iran.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study is to present the mortality
      trends of oesophageal cancer (EC) in the Iranian population, to provide updated
      information regarding time trends for this cancer. PATIENTS AND METHODS: We
      analysed the national death statistics reported by the Iranian Ministry of Health
      and Medical Education from 1995 to 2004. EC [International Classification of
      Diseases (ICD-9); C15] were expressed as the annual mortality rates/100000,
      overall, by sex and by age group (<15, 15-49 and >= 50 years of age) and age
      standardised rate (ASR). RESULTS: The age standardised mortality rate of EC
      increased dramatically during the study period. EC mortality was higher for males
      and the mortality rate also increased with age. CONCLUSION: This study provides a
      comprehensive projection for the burden of death due to EC, indicating that the
      trend of EC mortality dramatically increased in the recent decade.

PMID- 22980598
TI  - Gastric cancer and Helicobacter pylori infection in the eastern Libya: a
      descriptive epidemiological study.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to determine the pattern of
      histologically-proven gastric cancer in Eastern Libya and explore its association
      with Helicobacter pylori infection. PATIENTS AND METHODS: The registries of the
      Departments of Histopathology, Faculty of Medicine, Benghazi University and
      Oncology, Al-Jomhoria Hospital, Benghazi, were reviewed for cases with primary
      gastrointestinal cancer from January 2000 to December 2002 (sole Histopathology
      and Oncology Departments in Eastern Libya). Slides of hematoxylin and eosin stain
      of gastric cancer patients were re-stained to detect H. pylori. The American
      Joint Committee on Cancer Tumor, Node, Metastasis staging was used for clinical
      and pathologic staging. Gastric cancer biopsy materials were classified into
      intestinal or diffuse type according to Lauren criteria. RESULTS: One hundred and
      fourteen cases of gastric cancer were diagnosed. Tumor stages were: 2 (14%), 3
      (21%), 4 (57%) and unknown (8%). Most common site of involvement was the antrum
      (48%). Diffuse adenocarcinoma occurred in 56 patients (49.1%), intestinal
      adenocarcinoma in 46 (40.4%) and malignant gastric lymphoma in 12 (10.5%). The
      overall frequency of H. pylori infection was 63.2% (72/114), more frequent in
      intestinal adenocarcinoma (71.7%) and malignant lymphoma (66.6%) than diffuse
      adenocarcinoma (55.3%). The frequency of gastric cancer increased throughout the
      three years of study. CONCLUSION: The majority of the patients were diagnosed in
      locally advanced or metastatic stage. Clearly more efforts need to be given to
      early detection. We showed a stronger association of H. pylori infection with
      intestinal type gastric adenocarcinoma and malignant lymphoma than diffuse
      adenocarcinoma suggesting that H. pylori infection is the most probable causal
      factor of gastric cancer in this part of Libya.

PMID- 22980599
TI  - Choledochal cysts in Omani children: a case series.
AB  - BACKGROUND AND STUDY AIMS: Choledochal cysts (CCs) are rare congenital anomalies
      of the biliary tract with a low incidence in the western countries and a higher
      incidence in the eastern part of the world. CCs have female to male
      preponderance. CCs type distribution is known in certain parts of the world but
      very little is published about the common types of CCs and gender distribution in
      the Arab countries. We aim to describe the CC types and gender distribution in
      Omani children in one centre. PATIENTS AND METHODS: A retrospective review of all
      children diagnosed to have choledochal cysts over a 2 year period at a tertiary
      hospital in Oman. RESULTS: We diagnosed six children with CCs. The type
      distribution of CCs and gender preponderance in Omani children are not similar to
      what is described internationally. Type IV A was the most common type (50%) and
      less of type I (16.7%), unlike worldwide distribution. Female to male
      preponderance described in the literature is not seen in our case series. Fifty
      percent of our patients were boys. In this case series, we compare our results to
      the described case reports of CCs from Arab countries and Africa and bring up the
      difference. CONCLUSIONS: We demonstrate the unusual types of CCs and gender
      distribution in Omani children compared to the literature. To our best knowledge,
      this is the first case series of CCs in Omani children and the largest reported
      study in the literature in the Arab countries so far.

PMID- 22980600
TI  - Sclerosing mesenteritis: A rare case of large bowel and rectum involvement.
AB  - Sclerosing mesenteritis (SM) is an uncommon non-neoplastic inflammatory process
      in the mesentery that is seen as a pseudotumour, usually involving the small
      bowel mesentery and, less commonly, the mesentery of the large bowel. The disease
      has two well-established histological types: the acute or sub-acute form known as
      mesenteric panniculitis and the chronic form known as retractile or SM. Because
      SM lacks special clinical manifestation and typical signs, the possibility of
      misdiagnosis is very high. The correct diagnosis of SM depends on pathological
      examination. Here in, we report a case of a 41-year-old male patient with SM of
      the large bowel.

PMID- 22980601
TI  - Primary intestinal lymphangiectasia or Waldmann's disease: a rare cause of lower
      gastrointestinal bleeding.

PMID- 22980602
TI  - Endosonographic image of an oesophageal submucosal cyst.

PMID- 22980603
TI  - Giant aortic pseudoaneurysm complicating a case of chronic pancreatitis.

PMID- 22980604
TI  - An unusual case of solitary rectal ulcer syndrome mimicking inflammatory bowel
      disease and malignancy.

PMID- 22980605
TI  - Hepatitis D in Pakistan.

PMID- 22980606
TI  - Congenital heart defects associated with atrial heterotaxy.
AB  - OBJECTIVE: To determine the frequency of various congenital cardiac defects
      associated with atrial heterotaxy and the difference between spectrum of cardiac
      defects in right atrial isomerism (RAI) and left atrial isomerism (LAI) in these
      patients. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION
      OF STUDY: Department of Cardiology, The Children's Hospital and Institute of
      Child Health, Lahore, from July 2006 to June 2011. METHODOLOGY: All children
      presenting to the hospital with suspected congenital heart defect were included
      in the study. Echocardiography based sequential segmental analysis was used,
      taking atrial symmetry, interrupted inferior vena cava (IVC) and juxtaposed aorta
      to IVC relation into account for identifying atrial heterotaxy. Various segmental
      defects were noted for RAI and LAI. RESULTS: Children had atrial heterotaxy (M:F;
      1.7:1) with 61.6% (n=82) having LAI. Most common lesions associated with RAI
      included complete atrioventricular (AV) septal defect (n=48, 94.1%), single AV
      valve (n=45, 88.2%) and pulmonary outflow tract obstruction (n=41, 80.4%). LAI
      was associated with ventricular septal defect (n=68, 82.9%), atrial septal defect
      (n=63, 76.8%, mostly secundum variety), and miscellaneous left sided obstructive
      lesions. CONCLUSION: Atrial heterotaxy encompasses a wide spectrum of congenital
      cardiac defects. The frequency of various defects associated with RAI or LAI in
      local South Asian population of Lahore, Pakistan is similar to those as reported
      in the Western literature.

PMID- 22980607
TI  - Outcome of allogeneic haematopoietic stem cell transplantation in aplastic
      anaemia.
AB  - OBJECTIVE: To analyze factors associated with survival, rejection and graft
      versus host disease in aplastic anaemia patients undergoing allogeneic
      haematopoietic stem cell transplantation (SCT) from HLA matched sibling donors.
      STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Armed Forces Bone
      Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to June 2010.
      METHODOLOGY: Consecutive aplastic anaemia (AA) patients undergoing haematopoietic
      stem cell transplantation from HLA-matched sibling donors at this centre were
      included in this study. Potential factors affecting overall survival, rejection,
      disease-free survival and graft versus host disease were analyzed. Survival
      analysis was done by Kaplan-Meier method. Cox regression model was applied for
      multivariate analysis. RESULTS: Ninety male and thirty-five female patients with
      AA were included in the study. Median age was 18 years. Conditioning regimens
      used were cyclophosphamide (Cy) plus antilymphocyte globulin (ALG) or
      antithymocyte globulin (ATG), fludarabine (FLU) +Cy+ATG, Campath 1-H +Cy in 89,
      30 and 6 cases respectively. GVHD prophylaxis used was ciclosporin (CSA) plus
      prednisolone and short methotrexate in 81 while 44 received CSA plus
      prednisolone. At a median follow-up of 1185 days OS and DFS were 84% and 78%
      respectively. Factors associated with better OS were male sex, Flu/Cy/ATG
      conditioning and use of bone marrow as stem cell source. CONCLUSION: Flu/Cy/ATG
      conditioning regimen, bone marrow as stem cell source and CSA, prednisolone and
      short methotrexate regimen were associated with better survival in AA.

PMID- 22980608
TI  - PubMed-based quantitative analysis of biomedical publications in the SAARC
      countries: 1985-2009.
AB  - OBJECTIVE: To conduct a geographical analysis of biomedical publications from the
      South Asian Association for Regional Cooperation (SAARC) countries over the past
      25 years (1985-2009) using the PubMed database. STUDY DESIGN: A qualitative
      study. PLACE AND DURATION OF STUDY: Web-based search during September 2010.
      METHODOLOGY: A data extraction program, developed by one of the authors (SFS),
      was used to extract the raw publication counts from the downloaded PubMed data. A
      search of PubMed was performed for all journals indexed by selecting the advanced
      search option and entering the country name in the 'affiliation' field. The
      publications were normalized by total population, adult illiteracy rate, gross
      domestic product (GDP), secondary school enrollment ratio and Internet usage
      rate. RESULTS: The number of PubMed-listed papers published by the SAARC
      countries over the last 25 years totalled 141,783, which is 1.1% of the total
      papers indexed by PubMed in the same period. India alone produced 90.5% of total
      publications generated by SAARC countries. The average number of papers published
      per year from 1985 to 2009 was 5671 and number of publication increased
      approximately 242-fold. Normalizing by the population (per million) and GDP (per
      billion), India (133, 27.6%) and Nepal (323, 37.3%) had the highest publications
      respectively. CONCLUSION: There was a marked imbalance among the SAARC countries
      in terms of biomedical research and publication. Because of huge population and
      the high disease burden, biomedical research and publication output should
      receive special attention to formulate health policies, re-orient medical
      education curricula, and alleviate diseases and poverty.

PMID- 22980609
TI  - Human immunodeficiency virus type-1 (HIV-1) disease progression and viral
      activity: a seroepidemiological and molecular study.
AB  - OBJECTIVE: To determine the frequency and epidemiological characterization of
      human immunodeficiency virus type-1 (HIV-1) infection, HIV disease progression,
      immune status and viral activity. STUDY DESIGN: Descriptive study. PLACE AND
      DURATION OF STUDY: Department of Microbiology, University of the Punjab and
      Institute of Public Health, Lahore, from September 2005 to August 2008.
      METHODOLOGY: The study enrolled samples from general population, high risk groups
      and spouses of HIV+ deport workers with criteria; positive double enzyme linked
      immunosorbent assay (ELISA) and positive western blot. Immune status and viral
      activity was determined by cluster determinants (CD4+ and CD8+) cell count, ratio
      of CD4+/CD8+ on flow cytometer, and HIV RNA viral load on polymerase chain
      reaction (PCR). RESULTS: A total of 116 HIV+ untreated subjects enrolled after
      screening of 2260 blood samples. The seroprevalence rate in general population,
      high risk individuals and spouses of HIV+ deport workers was found 0%, 0.4% and
      26% respectively. The CD4+ cell count was found 533/mm3 (range 12-1800/mm3) and
      plasma viral load 27,122 copies/ml (range 00-40,621). The CD4+/CD8+ ratios < 0.5,
      < 1, < 1.5 and < 2 appeared as 17.2%, 30.2%, 51.7% and 0.9% respectively.
      Significant correlation was observed between plasma viral load, CD4+ count and
      CD4+/CD8+ ratio (p = 0.001). CD4+ T-cell counts < 200 cells/mm3 was found in 23
      HIV+ patients. CONCLUSION: There was a low frequency of HIV in the general
      population and high risks groups as compared to very high frequency in spouses of
      HIV+ deport workers with significant correlation of viral activity and immune
      status.

PMID- 22980610
TI  - Childhood primary angiitis of the central nervous system.
AB  - OBJECTIVE: To analyze the clinical course and magnetic resonance angiographic
      (MRA) abnormalities in children with primary angiitis of the central nervous
      system (cPACNS). STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY:
      Neurosciences and Neuroradiology Department of the Children's Hospital, Lahore,
      from January 2009 to December 2010. METHODOLOGY: The cohort comprised consecutive
      patients diagnosed as having cPACNS based on clinical findings and identification
      of arterial stenosis on magnetic resonance angiography (MRA) in the absence of an
      underlying condition that could cause these findings. The treatment protocol for
      ischaemic infarcts consisted of induction therapy with intravenous steroids
      pulses and intravenous immunoglobulin followed by maintenance therapy with
      azathioprine and low dose aspirin. When indicated, they were treated with
      anticoagulants at least for 4 weeks along with induction therapy. Patients were
      followed at a single centre and systemically assessed for clinical presentation,
      classification of disease as progressive or non-progressive, adverse effects of
      anticoagulants, aspirin, azathioprine and their hospital course. RESULTS: Sixty
      eight children with medium-large vessel cPACNS (62% boys, 38% girls) with mean
      age of 8.5 +/- 3.5 years were enrolled in this study. Motor deficit (70%);
      headache (64%) and fever (20%) were the commonest symptoms; whereas hemiparesis
      (60%); seizures 55% (focal 35%, generalized 20%) and decreased conscious level
      (30%), were the commonest neurological findings. Neuroradiological findings were
      ischaemic strokes in 50 (73.5%), haemorrhagic strokes in 10 (14.7%) and ischaemic
      haemorrhagic lesions in 8 cases (11.8%). Angiographically 51 (51/68, 75%) of the
      cohort had non-progressive (obliterative) and 17 (17/68, 25%) had evidence of
      progressive arteriopathy at the time of admission. No secondary haemorrhagic
      lesions were documented among infarcts strokes, which were treated with heparin
      and oral anticoagulants. Outcome was survival in 56 cases (81.5%) and death in 12
      cases (18.5%). All survivors were discharged on long-term oral aspirin; 15 of
      them were also commenced on azathioprine. Neurological findings among the 56
      survivors were; normal 20%, minor disabilities in 25%, moderate disabilities in
      20% and severe disabilities in 35%. CONCLUSION: The spectrum of cPACNS includes
      both progressive and non-progressive forms with significant morbidity and
      mortality. This treatment protocol of immunosuppressive therapy may improve long
      term neurological outcome in children with medium-large vessel childhood primary
      angiitis of the CNS.

PMID- 22980611
TI  - Complications of total hip replacement.
AB  - OBJECTIVE: To determine the factors causing complications in unilateral total hip
      replacement. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: The Aga
      Khan University Hospital, Karachi, between 2000 and 2010. METHODOLOGY: During the
      study period, 199 patients underwent elective unilateral total hip replacement at
      the Aga Khan University Hospital. Patients were divided into two groups on the
      basis of postoperative complications within 30 days of surgery. Significant
      factors at 5% significance level on univariate analysis were further analyzed by
      multivariate logistic regression. RESULTS: Postoperative complications occurred
      in 39 patients (19.6%); dislocation being most common in 13 patients (6.5%),
      followed by wound infection in four (2%), all of these patients required
      intervention. Other minor complications which were managed conservatively
      included wound infection (2.5%), urinary tract infection (2.5%), dislocation
      (1%), pleural effusion and pneumonia (2%), deep venous thrombosis (0.5%) and
      myocardial infarction (0.5%). On univariate analysis, patients with ASA III and
      IV, peri-operative blood transfusion, pre-operative hip deformity and post
      operative bisphosphonate use were significantly associated with complications. On
      multi-variate analysis, adjusted odd's ratio for perioperative transfusion (3;
      95% CI: 1.17-7.7) and hip deformity (3.2, 95% CI: 1.4-3.4) was found
      statistically significant. CONCLUSION: Pre-operative hip deformity and
      perioperative blood transfusion significantly influence the rates of complication
      after unilateral THR.

PMID- 22980612
TI  - Coblation adenotonsillectomy in children.
AB  - OBJECTIVE: To determine re-admission rate for post-tonsillectomy pain; the
      primary and secondary post-tonsillectomy bleeding rate; the percentage requiring
      control of post-tonsillectomy bleeding in children undergoing coblation
      tonsillectomy. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY:
      Royal Hospital for Sick Children (Yorkhill Hospital) between 2004 and 2006.
      METHODOLOGY: All patients who underwent tonsillectomy with or without
      adenoidectomy by coblation technique. Patients were identified from operation
      theatre log book and electronic data base of theatre activity. The hospital case
      notes were reviewed retrospectively to collect data, regarding demographics,
      indication and type of surgery, grade of operating surgeon, duration of hospital
      stay, re-attendance and re-admission, and management of complications. RESULTS: A
      total of 106 children; males (n = 53, 50%), females (n = 53, 50%) with a mean age
      6.3 years underwent surgery using coblation technique. Thirty-one percent had a
      tonsillectomy while 69% underwent an adenotonsillectomy. Of these, 48% had
      history of recurrent tonsillitis, 43% had obstructive sleep apnoea and 9%
      suffered predominantly from obstructive symptoms. Eighty-two percent of patients
      were discharged on the first postoperative day. Only one patient had primary
      bleeding requiring re-operation. After discharge, 7 patients (6.7%) were re
      admitted with secondary bleeding, 3 (2.8%) of whom were taken back to theatre to
      control the bleeding under general anaesthesia. CONCLUSION: Coblation
      tonsillectomy is a useful technique in having a low primary and secondary
      bleeding rates in children undergoing tonsillectomy and adenotonsillectomy.

PMID- 22980613
TI  - Distraction osteogenesis for correcting maxillo-mandibular deformities.
AB  - OBJECTIVE: To determine the effectiveness of distraction osteogenesis (DO) for
      correcting maxillofacial deformities. STUDY DESIGN: Case series. PLACE AND
      DURATION OF STUDY: Department of Oral and Maxillofacial Surgery, Armed Forces
      Institute of Dentistry, Rawalpindi, from June 2008 to November 2010. METHODOLOGY:
      Patients with diverse maxillofacial deformities were selected for the study. In
      all cases, intraoral distractors were used. Mandibular osteotomies were done
      using submandibular incision and maxillary osteotomy was done using standard
      vestibular incision. In paediatric patients, DO was started on third
      postoperative day while in adults, a 7-day latency period was followed.
      Distraction was carried out at a rate of 0.5 mm twice daily (1 mm/day).
      Distractors were removed after a consolidation period of 2 months. RESULTS: A
      total 7 cases were operated for DO. Out of these, 3 were males and 4 females. The
      age ranged from 2-24 years (mean 12.57 + 9.48 years). Five patients had their
      deformity owing to temporo mandibular joint (TMJ) ankylosis, one had congenital
      micrognathia and one patient had skeletal class-III deformity. Five patients
      underwent mandibular DO, one underwent maxillary DO and in one case simultaneous
      maxillo-mandibular DO was carried out. Amount of distraction varied from 9.0 mm
      to 19.2 mm (mean 15.04 + 4.33 mm). Mean follow-up was 18.14 + 5.39 months.
      CONCLUSION: Distraction osteogenesis can be employed satisfactorily to correct
      diverse maxillofacial deformities like retrognathia, facial asymmetry and
      skeletal class-III.

PMID- 22980614
TI  - Migration of health workers: a challenge for health care system.
AB  - The migration of health workers has resulted in a growing apprehension
      universally because of its impact on health system of the developing countries.
      Although the choice to migrate is basically a personal one, however, the overall
      social and economic circumstances have important impact on the decision to
      migrate. The "push and pull" factors for migration are disparity in working
      conditions, pay, lack of promotion opportunities, poor living conditions, desire
      to gain experience, professional development, family background and family
      wealth. A strategic approach by the government and other agencies is mandatory
      for regulating the flow of health workers between countries. A range of policies
      and interventions are needed to deal with the broader health system issue and
      problems of health workers that influence their recruitment, retention,
      deployment and progress.

PMID- 22980615
TI  - Parathyroid carcinoma.
AB  - Parathyroid carcinoma is a rare endocrine malignancy accounting for less than 1%
      of all cases of hyperparathyroidism. We present a case of a middle-aged woman who
      was undiagnosed for 3 years before presenting with renal stones and advanced
      musculoskeletal disease. Investigations revealed primary hyperparathyroidism.
      Focused cervical exploration and left inferior parathyroidectomy was carried out
      based on the pre-operative localization studies. Parathyroid carcinoma was
      diagnosed on histopathology postoperatively. Subsequent en bloc resection was not
      performed and the patient is being monitored with serial parathyroid hormone
      levels which have not shown any increase in 6 months of follow-up. Only two
      previous cases of parathyroid carcinoma have been reported from Pakistan.

PMID- 22980616
TI  - Post-traumatic arteriovenous fistula reporting with haematuria after 25 years.
AB  - A case of post-traumatic arteriovenous fistula in the left thigh is reported 25
      years after injury with haematuria. The patient had sustained bullet injury in
      his left thigh in 1986. Clinically, he had thrill and bruit in his left thigh and
      groin. Ultrasound abdomen and pelvis revealed a vascular mass in the left side of
      urinary bladder. CT angiography showed communication between left superficial
      femoral artery and vein and gross dilatation of thigh and pelvic veins with mass
      effect on the urinary bladder. He was managed by excision of fistula and repair
      of both artery and vein with interposition of a prosthetic graft.

PMID- 22980617
TI  - Temozolomide for relapsed primary CNS lymphoma.
AB  - Primary CNS lymphoma (PCNSL) is an aggressive form of non-Hodgkin's lymphoma that
      accounts for 3% of all primary brain tumours. No clear risk factors for PCNSL in
      immunocompetent patients are known. The disease is more common in men and in
      elderly persons. Patients with AIDS who have low CD4+ counts are at the greatest
      risk for PCNSL. Virtually all PCNSLs in patients with AIDS express an Epstein
      Barr virus (EBV)-related genome. PCNSL is less frequently associated with EBV in
      patients without AIDS. A 42 years old gentleman diagnosed with primary CNS
      lymphoma with negative serological test for human immunodeficiency virus was
      initially treated with Modified De Angelis protocol relapsed after treatment. He
      underwent gamma knife stereotactic surgery which lead to further deterioration
      clinically and progression of disease on imaging. Later, he was treated with
      salvage high dose methotrexate, but after completion of six cycles there was a
      radiological progression of disease. Relapsed disease was further treated with a
      single agent temozolomide and the disease went in remission.

PMID- 22980618
TI  - Gemtuzumab-induced orchitis in a patient with refractory acute promyelocytic
      leukaemia.
AB  - We report the case of a 22-year-old Saudi male patient who was treated
      extensively in the past with various regimens for acute promyelocytic leukaemia
      that was refractory to all standard treatments. He was ultimately administered
      Gemtuzumab to induce remission and subjected to an allogeneic bone marrow
      transplant. However, he developed orchitis, which has not been previously
      reported with this agent.

PMID- 22980619
TI  - Total hip arthroplasty for childhood fused hip.
AB  - The conversion of a painless fused hip of a long standing duration to a mobile
      hip is usually not demanded due to a number of per-operative problems, iatrogenic
      complications and a high demanding procedure. The conversion is, however,
      required when a patient develops chronic back pain or a painful pseudoarthrosis
      of the hip. Conversion due to pseudoarthrosis in a recent fracture through
      femoral neck of previously fused painless hip has never been reported. We are
      reporting this unique indication for conversion.

PMID- 22980620
TI  - Endoscopy in rhinolithiasis.
AB  - Rhinolith is a stone like nasal mass uncommon in children and adolescent.
      Diagnosis of rhinolithiasis may be difficult because of the possibility of
      varying clinical presentations. We report 2 cases in adults. The first was 23
      years old female having unilateral nasal obstruction, cacosmia and occasional
      blood stained nasal discharge. The second case was that of a 47 years old male
      having unilateral foul smelling nasal discharge, progressive unilateral nasal
      obstruction, anosmia and atypical facial pain. Both were diagnosed on anterior
      rhinoscopy and rigid endoscopic examination of nose. Radiological evaluation of
      nose and paranasal sinuses were performed to confirm the diagnosis. These
      rhinoliths were removed using zero degrees  rigid nasal endoscope. Salient
      features of such large rhinoliths and the role of rigid endoscope in the
      diagnosis and treatment are discussed briefly enabling the attending physician to
      be aware of this infrequent entity in adults which requires high index of
      suspicion.

PMID- 22980621
TI  - Carcinoid tumour of the middle ear.
AB  - A case of middle ear mass in a young female from Ireland is described, who
      presented with left ear hearing loss and intermittent bloody discharge from the
      same ear. Examination under microscope revealed occlusive polyp in the left ear
      and a biopsy had been taken under general anaesthesia. Histopathology report
      described an adenoma / carcinoid tumour of the middle ear confirmed by positive
      immunohistochemical staining. CT temporal bones revealed the extension of the
      disease. The patient underwent left tympanotomy and excision of the tumour. In
      general, these tumours are regarded as benign but may be mistaken for
      adenocarcinomas because of their histological heterogenecity.

PMID- 22980622
TI  - Cerebro-oculo-facio-skeletal syndrome.
AB  - Cerebro-oculo-facio-skeletal syndrome (COFSS) is a recessively inherited
      neurodegenerative disorder. We describe an 8 months old Saudi girl, a product of
      consanguineous parents with unremarkable pre-natal and postnatal history and
      birth weight 2 kg. She was having microcephaly, micrognathia, micro-ophthalmia,
      large low set ears, upper lip overhanging the lower lip and congenital
      contractures. Growth and development were severely retarded. MRI and MRS
      (magnetic resonance spectrometry) of brain displayed severe brain atrophy and
      hypo/demyelination of white matter. The relationship between COFSS and
      differential diagnoses, Cockayne syndrome (CS), Pena-Shokier phenotype (PSP) and
      Neu-Lexova syndrome (NLS) are discussed. Pre-natal diagnosis followed by
      appropriate management in time may be helpful to reduce its incidence in the
      community.

PMID- 22980623
TI  - Seropositivity of hepatitis C, hepatitis B and HIV in chronically transfused beta
      thalassaemia major patients.
AB  - The purpose of this study was to determine the frequency and trend of transfusion
      transmitted infections (TTI) in chronically transfused beta-thalassaemia major
      (TM) patients with reference to the duration of transfusions. A cross-sectional
      study was done on 160 beta-TM patients and 5517 healthy blood donors to find out
      the prevalence of HCV, HBV and HIV infections. Out of 160 patients, 21 cases
      (13.1%) were anti-HCV positive, 2 (1.25%) were HBsAg positive. HIV antibodies
      were not detected in any sample. However, 109 (1.9%) and 104 (1.8%) of 5517 blood
      donors were positive for HCV and HBV respectively. No donor showed HIV
      antibodies. Anti-HCV was positive in 9/111(8.4%) thalassaemics (< 10 years of
      age) while 11/49 (22%) [> 10 years of age] showing significant difference (p =
      0.005) among the two groups. For the past 10 - 12 years the screening of blood
      has reduced the magnitude of the disease significantly as shown by the trend in
      two age groups. Further improvements need to be done to implement uniform
      screening throughout the country.

PMID- 22980624
TI  - A simple working type classification proposed for the psychosomatic disorders of
      the oral cavity.

PMID- 22980625
TI  - Skin tag (acrochordon) on labium majus in an infertile female.

PMID- 22980626
TI  - Spontaneous Kommerell diverticulum dissection.

PMID- 22980627
TI  - AATS 2012: "To model excellence".

PMID- 22980628
TI  - Historical perspectives of The American Association for Thoracic Surgery: Dwight
      C. McGoon (1925-1999).

PMID- 22980629
TI  - Initial experience with a new technique of endoscopic and ultrasonographic access
      for biopsy of para-aortic (station 6) mediastinal lymph nodes without traversing
      the aorta.
AB  - OBJECTIVES: All lymph node stations but the para-aortic are accessible by a
      combination of endoscopic ultrasound and endobronchial ultrasound. We recently
      described an echographic-endoscopic technique for the biopsy of para-aortic
      (station 6) lymph nodes without traversing the thoracic aorta. This study
      reviewed our initial experience with this new technique. METHODS: This first-in
      human evaluation of the biopsy of station 6 mediastinal lymph nodes with
      curvilinear endoscopic ultrasound without arterial puncture used a retrospective
      case series design to study 12 consecutive patients who underwent this new
      technique. Station 6 lymph nodes were approached with a long fine needle
      aspiration approach (6-8 cm) through the proximal esophagus. The needle was
      passed through the esophagus into the mediastinum just medial to the left
      subclavian artery. It was then directed toward the para-aortic location (6-8 cm
      trajectory) to reach and enter the para-aortic lymph nodes without piercing the
      aorta or great vessels. RESULTS: Successful cytologic diagnoses of station 6
      lymph nodes were obtained in all cases (lymphocytes in all samples). No morbidity
      resulted from the procedure, nor was any observed at 30 days after the procedure.
      Patient anatomy may preclude safe access in certain situations. CONCLUSIONS:
      Endoscopic ultrasound access of para-aortic (station 6) lymph nodes allows
      complete, minimally invasive mediastinal lymph node staging and diagnosis without
      traversal of the aorta. This technique, the final piece of the puzzle required
      for complete staging of the mediastinum with nonsurgical endoscopic techniques,
      is reproducible and safe.

PMID- 22980631
TI  - Introduction to the Single Ventricle Reconstruction trial.

PMID- 22980632
TI  - Direct visualization of the aortic cusp from the left ventricle during aortic
      root reimplantation.

PMID- 22980633
TI  - Is aggressive distal repair necessary in aortic dissection surgery?

PMID- 22980635
TI  - Women's autonomy and unintended pregnancies in the Philippines.
AB  - To date, very few studies have examined what contributes to unwanted and mistimed
      births in the Philippines. In a country where women have higher educational
      levels than their male counterparts, and their status is among the highest in
      Asia, it is expected that unwanted births will be low. The evidence, however,
      points to the contrary as 44% of births reported in the last five years were
      unintended. Using the 2003 Philippines National Demographic and Health Survey,
      this article focuses on married women who are currently pregnant and those who
      had given birth in the last five years. Multinomial logistic regression is
      employed to ascertain the risks of a recent birth/pregnancy being unwanted,
      mistimed or wanted. Regardless of women's status, having a final say in household
      and sexual matters with husbands lowers the risk of unwanted births but not
      mistimed births, calling into question the use of status variables such as
      education and wealth as indicators of women's autonomy. The success of
      implementing family planning programmes and policies in reducing unintended
      pregnancies underscores the importance of understanding how women are able (or
      unable) to make decisions surrounding their reproductive intentions.

PMID- 22980637
TI  - Target-based selection of flavonoids for neurodegenerative disorders.
AB  - Habitual consumption of dietary flavonoids known to improve mitochondrial
      bioenergetics and inhibit various secondary sources of reactive oxygen species
      (ROS) reduces the risk for neurodegenerative disorders such as Parkinson's
      disease (PD), stroke, and Alzheimer's disease (AD). Combining specific dietary
      flavonoids selected on the basis of oral bioavailability, brain penetration, and
      the inhibition of multiple processes responsible for excessive ROS production may
      be a viable approach for the prevention and treatment of neurodegenerative
      disorders. Inclusion of flavonoids that raise cAMP levels in the brain may be of
      additional benefit by reducing the production of proinflammatory mediators and
      stimulating the transcriptional machinery necessary for mitochondrial
      biosynthesis. Preclinical models suggest that flavonoids reduce hearing loss
      resulting from treatment with the chemotherapeutic drug cisplatin by opposing the
      excessive production of ROS and proinflammatory mediators implicated in PD,
      stroke, and AD. Flavonoid combinations optimized for efficacy in models of
      cisplatin-induced hearing loss (CIHL) may therefore have therapeutic utility for
      neurodegenerative disorders.

PMID- 22980639
TI  - Effect of femtosecond laser fragmentation of the nucleus with different softening
      grid sizes on effective phaco time in cataract surgery.
AB  - PURPOSE: To compare the effect of different fragmentation softening grids in
      femtosecond laser-assisted cataract surgery on effective phacoemulsification time
      (EPT). SETTING: Ruhr University Eye Clinic, Bochum, Germany. DESIGN: Prospective
      randomized clinical trial. METHODS: The study evaluated the feasibility of using
      a femtosecond laser (Catalys Precision Laser System) to perform capsulotomy and
      lens fragmentation in the treatment of patients with senile cataract. Patients
      were evaluated preoperatively with the Lens Opacities Classification System III
      (LOCS III). Patients had laser refractive cataract surgery with 350 MUm
      fragmentation grids or with 500 MUm fragmentation grids. Both groups had
      phacoemulsification using pulsed ultrasound energy, and the EPT was evaluated.
      RESULTS: Eighty patients were treated with 350 MUm fragmentation grids and 80
      patients with 500 MUm fragmentation grids. The mean preoperative LOCS III grade
      was 3.7 +/- 0.8 (SD) in the 350 MUm group and 3.5 +/- 0.8 in the 500 MUm group.
      The mean laser treatment time was 66.4 +/- 14.4 seconds in the 350 MUm group and
      52.8 +/- 11.9 seconds in the 500 MUm grid group and the mean EPT, 0.03 +/- 0.05
      seconds and 0.21 +/- 0.26 seconds, respectively. CONCLUSION: The use of the
      femtosecond laser-assisted system in cataract surgery with 350 MUm grid softening
      led to a statistically significant lower EPT than the 500 MUm grid. FINANCIAL
      DISCLOSURE: Dr. Dick is a member of the medical advisory board of Optimedica
      Corp. No other author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 22980641
TI  - Ultra-high performance liquid chromatography coupled to high resolution Orbitrap
      mass spectrometry for metabolomic profiling of the endogenous phytohormonal
      status of the tomato plant.
AB  - Phytohormones are key signalling biomolecules and are of particular interest
      because of their regulating role in numerous physiological and developmental
      plant processes. Since the plant response to a given stimulus results amongst
      others from the complex interaction between phytohormones, there is a mounting
      interest for multiple phytohormone analysis. Therefore, with the primary aim of
      profiling the hormonal status of the tomato plant, a generic extraction protocol
      and an U-HPLC-Orbitrap-MS analysis were developed and validated for both tomato
      fruit and leaf tissue. To this end, eight phytohormones were considered, i.e.
      gibberellic acid, indol-3-acetic acid, abscisic acid, jasmonic acid, salicylic
      acid, zeatin, N6-benzyladenine and epibrassinolide, representing the major
      hormonal classes. The sample pre-treatment involved liquid extraction with a
      buffer of methanol, ultrapure water and formic acid (75:20:5, v/v/v), after which
      the extract was purified by means of an Amicon(r) Ultra centrifugal unit.
      Subsequently, analytes were chromatographically separated on a sub-2 MUm
      particles Nucleodur Gravity C18 column and detected by an ExactiveTM high
      resolution mass spectrometer. Validation of the analytical method demonstrated
      that linearity (>=0.99), precision (CV<=15%) and mean corrected recovery (between
      80% and 110%) performed well for the majority of the eight targeted
      phytohormones. In addition, the generic nature of the extraction protocol and the
      full scan approach of the Orbitrap mass spectrometer allowed metabolomic
      profiling of the hormonal status of the tomato plant.

PMID- 22980642
TI  - Process scale separation of an anti-CD22 immunotoxin charge variant.
AB  - We describe the analytical characterization and process scale separation of a
      deamidated variant of an immunotoxin. The different charge variants of the
      immunotoxin were separated using analytical ion-exchange HPLC. These charge
      variants were analyzed by peptide mapping and LC-MS/MS to identify the site of
      modification, which was determined to reside in the toxin portion of the
      molecule. Using a cell-based bioassay it was also determined that deamidation led
      to reduced biological activity, requiring it be controlled during manufacturing.
      This was accomplished using process scale anion-exchange chromatography. The
      process was capable of reducing the deamidated form to a level low enough for the
      resulting product to maintain acceptable biological activity. Keys to the
      successful control of this impurity at process scale were a good understanding of
      structure-function relationship and the availability of an analytical HPLC assay
      to provide a surrogate for the cell-based bioassay.

PMID- 22980643
TI  - Investigation of protocols to extraction and quantification of folates in
      vegetables matrices split into liquor and fiber fraction using factorial design.
AB  - The main protocols of extraction were investigated for the six folate forms in
      vegetable matrices, treated in two fractions, liquor and fiber. In a pilot study,
      it was used ammonium acetate added of 2-mercaptoetanol and ascorbic acid as
      extraction solution. The condition of use of protease and folate conjugase was
      evaluated, besides alternative treatments without enzyme use. Based on the
      results of this stage, it was built the factorial design 2(4), with three
      replications at the central point, using the following variables: temperature,
      time for reaction, molar concentration of the extraction solution and ratio
      sample/solution as independent variables and dependent variable, the amount of
      each folate form extracted as well as spectral and chromatographic parameters. In
      the pilot study it was verified that the enzyme use can cause an increase in the
      variability of the folate content, which enabled to build the factorial design
      without the enzyme use. The binomial time and temperature showed greatest impact
      on the extraction profile, besides high concentrations of ammonium acetate
      resulting in bifurcation of some peaks. 5-Methyltetrahydrofolate was extracted
      primordially in the liquor fraction, indicating that this treatment on the matrix
      provoked suitable extraction condition to this folate.

PMID- 22980644
TI  - Relay simulated moving bed chromatography: concept and design criteria.
AB  - We present a new class of multicolumn chromatographic processes that change the
      classical way of handling the product outlets of simulated moving-bed (SMB)
      chromatography to avoid the use of flow controllers or an extra pump-the
      objective is to have just two- or three-way valves at a column outlet-while
      maintaining the analogy with the SMB in terms of displaced volumes of fluid per
      switch interval. In this class of processes the flow through a zone (or column)
      is always in one of the three states: (i) frozen, (ii) completely directed to the
      next zone (or column), or (iii) entirely diverted to a product line. We use the
      term relayed stream to refer to this particular type of manipulation of the
      outflow from a column. For this class of processes we derive a SMB analog-the R
      SMB process-and demonstrate, under the framework of the equilibrium theory, that
      this process has the same separation region as the classical SMB for linear
      adsorption systems. In addition, the results from the equilibrium theory show
      that the R-SMB process consists of two distinct cycles that differ only in their
      intermediate sub-step: one cycle for selectivities alpha smaller than (3+?5)/2
      and another cycle for larger values of alpha; in the former case no product
      stream is collected during the intermediate sub-step, whereas in the latter case
      both product streams are collected. We also examine the R-SMB process under
      conditions of finite column efficiency and compare its performance against those
      of the classical open- and closed-loop SMBs. Our simulation results show that the
      R-SMB process requires less desorbent and is more productive than the standard
      SMB processes under conditions of finite column efficiency and that the
      comparison increasingly favors the R-SMB as the column efficiency decreases.

PMID- 22980646
TI  - Mass spectrometry: Innovation and application. Part VII.

PMID- 22980645
TI  - A simple graphical representation of selectivity in hydrophilic interaction
      liquid chromatography.
AB  - This paper uses the HILIC selectivity data of Dinh et al. (J. Chromatogr. A 1218
      (2011) 5880) to yield simple and easy to understand plots analogous to Neue plots
      for selectivity in HILIC. The plots categorize 21 previously studied HILIC phases
      (data from Dinh et al.), 8 additional HILIC columns and 4 reversed phase columns
      (our data) using selected probes for specific interactions. The relative
      retention of cytosine vs. uracil is used to probe the "hydrophilicity" of the
      HILIC phases; adenosine vs. adenine is used to probe the ability of the
      stationary phase to participate in hydrogen bonding; and benzyltrimethylammonium
      (BTMA) vs. cytosine is used to probe the cation exchange and anion exchange
      character of the column. Plots of kBTMA/kcytosine vs. kcytosine/kuracil
      successfully classify silica, amide, zwitterionic, diol and reverse phase columns
      in terms of their HILIC behavior. Polymeric columns including polymer substrate
      and polymer coated columns show low ion exchange character, but vary widely in
      their hydrophilicity. Alternatively a HILIC-Phase Selectivity Chart, in analogy
      to the Neue plot, is constructed by plotting log(kBTMA/kcytosine) vs.
      log(kcytosine). This plot enables classification of HILIC columns that will yield
      similar or significantly different separations.

PMID- 22980648
TI  - [Effect of IL-17 on collagen I/III expression in cardiac fibroblasts isolated
      from BALB/c mice].
AB  - AIM: To investigate the effect of IL-17 on the expression of collagen I/III in
      cardiac fibroblasts and analyze its molecular mechanism. METHODS: Cardiac
      fibroblasts were isolated from 7-14-day-old BALB/c mice and cultured in DMEM with
      10% fetal bovine serum (FBS). The cells were collected after IL-17 treatment for
      0,  24,  48,  72 h. IL-17 receptors on cardiac fibroblasts were detected by PCR; 
      the collagen I/III expression was analyzed by immunofluorescence;  the PKCbeta, 
      Erk1/2,  NF-kappaB phosphorylation were investigated by Western blotting.
      RESULTS: IL-17RA/C was expressed on cardiac fibroblasts;  after 24 h of IL-17
      stimulation,  the collagen I/III expression obviously increased;  Western
      blotting showed that PKCbeta,  Erk1/2 and NF-kappaB were phosphorylated on 30, 
      45,  45 min,  respectively. CONCLUSION: IL-17 could induce the expression of
      collagen I/III in cardiac fibroblasts,  which might be related with PKCbeta
      ERK1/2-NF-kappaB phosphorylation.

PMID- 22980649
TI  - [Induction of anti-hepatocellular carcinoma immunity by Hyper-IL-6 gene in vivo].
AB  - AIM: To prepare the mouse hepatocellular carcinoma (HCC) cells with the stable
      expression of Hyper-IL-6 and explore the possibility of inducing active anti-HCC
      immune response by Hyper-IL-6 gene. METHODS: Hyper-IL-6 gene was transfected into
      mouse HCC cells MM45T.Li using Lipofectamine(TM);2000. G418-resistant clones
      named MM45T-HIL-6 were selected and detected for the expression of Hyper-IL-6
      gene by RT-PCR and ELISA. Mouse HCC cells transfected with pEGFP-C1,  named MM45T
      mock,  were prepared as controls. Tumor models were established by injecting
      subcutaneously 5*10(5); cells of MM45T.Li,  MM45T- mock and MM45T-HIL-6 on the
      right anterior limb of BALB/c mouse,  respectively. In vivo experiments were
      performed to observe the tumorigenicity of MM45T.Li,  MM45T-mock and MM45T-HIL-6.
      The levels of CD4(+); and CD8(+); T cells in mouse peripheral blood were detected
      by flow cytometry (FCM). RESULTS: RT-PCR and ELISA showed that Hyper-IL-6 gene
      was expressed in the MM45T-HIL-6 cells,  but not in the control cells. We
      observed that the tumorigenicity of MM45T-HIL-6 decreased compared with control
      cells after they were inoculated subcutaneously into mice. FCM results indicated
      that the levels of CD4(+); and CD8(+); T cells in the peripheral blood
      significantly increased in the mice inoculated with MM45T-HIL-6 compared with the
      ones inoculated with MM45T.Li and MM45T-mock cells (P<0.05). CONCLUSION: The
      mouse HCC cells with the stable expression of Hyper-IL-6 can induce active anti
      HCC immune response after inoculated subcutaneously into mice.

PMID- 22980650
TI  - [Construction of recombinant adenovirus expressing shRNA targeting human 
      leukocyte-derived arginine aminopeptidase gene].
AB  - AIM: To construct the recombinant adenovirus expressing small hairpin RNA (shRNA)
      targeting human leukocyte-derived arginine aminopeptidase (LRAP) gene and silence
      the expression of LRAP in human retinal microvascular endothelial cells (HRMECs).
      METHODS: Three pairs of oligonucleotides coding for shRNAs targeting human LRAP
      gene were designed and synthesized,  and were cloned into the shuttle vector
      pRNAT-H1.1/Adeno after  annealing. The three constructed shuttle plasmids, 
      through homologous recombination with adenoviral backbone vector pAdEasy-1,  were
      transformed into E.coli BJ5183-AD-  to produce recombinant adenoviral plasmids.
      And then the recombinants linearized with Pac I were transfected into 293a cells
      to package adenoviruses. After amplification and titter determination,  the
      recombinant adenoviruses were used to infect the primary HRMECs. Quantitative
      real-time PCR was taken to determine the relative amount of LRAP mRNA to screen
      the adenovirus with the highest silencing efficiency. The level of LRAP protein
      after RNA interference in HRMECs was further determined by Western blotting.
      RESULTS: PCR,  restriction digestion and DNA sequencing confirmed that the
      purpose shRNA-coding sequences were correctly inserted into the shuttle vectors
      and adenoviral plasmids,  and the recombinant adenoviruses were packaged
      successfully in 293a cells. The most effective adenovirus   with the silencing
      efficiency up to 79% was selected by quantitative real-time PCR,  which
      significantly lowered the expression of LRAP in HRMECs. CONCLUSION: The
      recombinant adenovirus expressing shRNA effectively silencing LRAP gene was
      constructed successfully,  which would facilitate further study of the role that
      LRAP plays in the development of diabetic retinopathy.

PMID- 22980651
TI  - [Protective effect of lipoxin A4 against rhabdomyolysis-induced acute kidney
      injury in rats].
AB  - AIM: To investigate the protective effect of lipoxin A4 (LXA(4);) against
      rhabdomyolysis-induced acute kidney injury (AKI) and the possible mechanism.
      METHODS: The animal model of AKI was produced by intramuscular injection with
      glycerol. SD rats were randomly divided into 3 groups: the normal, AKI and
      LXA(4); groups. Blood urea nitrogen and serum creatinine levels were evaluated
      using a HITACHI 747 automatic analyzer. For histological examination, sections
      were stained with HE. The activity of myeloperoxidase (MPO) was detected by
      spectrophotometer. Expressions of TNF-alpha, IL-6 were determined by ELISA, and
      NF-kappaB in renal tissues was detected by Western blot analysis. RESULTS: The
      levels of blood urea nitrogen and serum creatinine decreased, and the injury of
      kidney was improved significantly in rats treated with LXA(4); as compared with
      AKI rats (P<0.05). The levels of TNF-alpha and IL-6, the activity of MPO and the
      expression of NF-kappaB were significantly lower in LXA(4); group than in AKI
      group (P<0.05). CONCLUSION: LXA(4);  can significantly protect rats against AKI
      partly by blocking NF-kappaB activation and reducing inflammatory cytokine
      expression and inflammatory cells infiltration in the kidney.

PMID- 22980652
TI  - [Effects of resveratrol on the morphology of lipid droplets and the expression of
      lipid droplet-associated proteins in mouse primary hepatocytes].
AB  - AIM: To investigate the effects of resveratrol on the morphology of lipid droplet
      (LD) and the expression of lipid droplet-associated proteins in primary
      hepatocytes of mice. METHODS: We isolated and cultured the primary hepatocytes of
      mice using collagenase perfusion. The primary hepatocytes were stimulated with
      200 MUmol/L oleic acid (OA) for 12 h, and then added with 0 (control), 20, 50,
      100 MUmol/L resveratrol, respectively. Another 12 h later, we utilized Bodipy
      493/503 staining to observe the morphology and amount of intracellular lipid
      droplets under fluorescence microscope. The Folch method and triglyceride (TG)
      quantitative kit were used to extract the total intracellular lipids and
      determine the TG contents. Western blotting was applied to analyze the expression
      levels of perilipin, adipophilin and TIP-47. RESULTS: Compared with the control,
      the size and amount of lipid droplets in primary hepatocytes were reduced after
      treated with different concentrations of resveratrol. The quantitative analysis
      showed that the intracellular TG contents decreased markedly in a dose-dependent
      manner, but the most significant decrease was in 50 MUmol/L resveratrol group.
      Western blotting showed that resveratrol reduced the expressions of perilipin,
      adipophilin and TIP-47 in the primary hepatocytes, especially the perilipin.
      CONCLUSION: Resveratrol could inhibit intracellular lipid accumulation, which is
      most significant in 50 MUmol/L concentration. The inhibiting effect of
      resveratrol may be caused by mediating the expression levels of lipid droplet
      associated proteins in primary hepatocytes of mice.

PMID- 22980653
TI  - [Effect of glycyrrhetinic acid on the expression of inflammatory factors in
      fibroblast-like synovial cells from collagen induced arthritis rats].
AB  - AIM: To determine the effects of glycyrrhetinic acid (GA), methotrexate(MTX) and
      GA+MTX on the expressions of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) in fibroblast-like synovial (FLS) cells from
      collagen induced arthritis (CIA) rats. METHODS: CIA-FLS cells were isolated and
      purified from the synovium of CIA rats by tissue block  culture method, and then
      treated with MTX, GA, GA+MTX or nothing (control group), respectively. Each group
      was cultured for 3 different time periods (1, 3, 5 d). Real-time qPCR was used to
      detect the expressions of TNF-alpha and IL-1beta mRNA in CIA-FLS cells and ELISA
      to determine the levels of TNF-alpha and IL-1beta in the supernatant. RESULTS:
      Day 1: No significant down-regulation of TNF-alpha and IL-1beta mRNA was
      identified in intervention groups compared with the control group (P>0.05); Day
      3: Intervention groups significantly down-regulated TNF-alpha and IL-1beta mRNA
      (P<0.05 vs control), but without intergroup difference(P>0.05); Day 5: the three
      intervention groups all suppressed the expressions of TNF-alpha and IL-1beta
      mRNA(P<0.05 vs control), with GA+MTX>MTX>GA in inhibiting effect (P<0.05). All
      intervention groups were found to inhibit the expressions of TNF-alpha and IL
      1beta in a time-dependent manner (P<0.05). Similar outcomes were observed in the
      change of the levels of TNF-alpha and IL-1beta in cell culture supernatant by
      ELISA. CONCLUSION: GA, MTX, GA+MTX suppress the expression of TNF-alpha and IL
      1beta in CIA-FLS cells in a time-dependent manner, and the suppressing effect is
      GA+MTX>MTX>GA.

PMID- 22980654
TI  - [IL-12-induced expression of TRAIL enhances the cytotoxicity of NK cells against
      Jurkat cells].
AB  - AIM: To study the mechanism underlying the IL-12-induced cytotoxic function of NK
      cells to Jurkat cells. METHODS: NK cells from peripheral blood mononuclear cells
      (PBMCs) were purified by magnetic sorting  and stimulated with or without IL-12.
      The expression of genes on IL-12-treated and non-IL-12-treated NK cells was
      analyzed by gene chips and the expression of cytolytic molecules was evaluated by
      flow cytometry. RESULTS: Seventeen genes were up- (5/17) or down-regulated
      (12/17) on IL-12-treated NK cells compared with non-IL-12-treated NK cells (fold
      change>=10). IL-12-induced expression of TRAIL on NK cells mediated the
      cytotoxicity to Jurkat cells. The expression of TRAIL on subsets of
      CD56(+);CD16(+); and CD56(-);CD16(+); NK cells significantly increased after the
      stimulation with IL-12 and Jurkat cells expressed high level of TRAIL receptor 2
      (TRAIL-R2). Importantly, the neutralizing mAbs against TRAIL (RIK-2)
      significantly inhibited the cytotoxicity of NK cells induced by IL-12.
      CONCLUSION: The expression of TRAIL on human NK cells induced by IL-12 was one of
      the major mechanisms of cytotoxicity to Jurkat cells.

PMID- 22980655
TI  - [Impact of anti-OX-LDL antibodies on   CD36 mRNA expression in monocytes].
AB  - AIM: To investigate the impact of antibodies to oxidized low-density lipoprotein
      (OX-LDL) on CD36 mRNA expression in monocytes and explore the mechanism
      underlying the impact on the formation of foam cells. METHODS: U937 cells and the
      monocytes of New Zealand rabbit were respectively cultured in vitro and divided
      into 4 groups: the control group (cultured in nutrient medium of RPMI1640), the
      OX-LDL group (with additional OX-LDL of 50 MUg/L in nutrient medium), the OX
      LDL+Ab-OX-LDL group (with additional OX-LDL of 50 MUg/L and Ab-OX-LDL of 100
      MUg/L in nutrient medium) and the Ab-OX-LDL group (with additional Ab-OX-LDL of
      100 MUg/L in nutrient medium). After 24-hour culture, the expression of CD36 mRNA
      was detected by semi-quantitative RT-PCR. RESULTS: The expression of CD36 mRNA,
      either in the OX-LDL group or in the OX-LDL+Ab-OX-LDL group, was higher than that
      in the control group. After intervened by Ab-OX-LDL, the expression was
      respectively down-regulated by 64.80% in U937 cells and 35.18% in the monocytes
      of rabbit, which was statistically significant between the two species.
      CONCLUSION: Antibodies to OX-LDL could negatively regulate the expression of CD36
      mRNA in monocytes, and prevent monocyte in taking OX-LDL through the pathway of
      antigen CD36.

PMID- 22980656
TI  - [Downregulation of HSP70 gene expression and apoptosis in human hepatocellular
      carcinoma SMMC-7721 cells induced by nimesulide in vitro].
AB  - AIM: To investigate the effect of nimesulide on cell apoptosis and possible
      mechanism in human hepatocellular carcinoma SMMC-7721 cells. METHODS: SMMC-7721
      cells were treated with nimesulide at different concentrations. Cell viability
      was assessed by MTT assay. Cell apoptosis rate was determined with flow
      cytometry.  The cleavage activity of PARP and caspase-9 and the expression of
      HSP70 were  evaluated using RT-PCR and Western blotting. The influence of  HSP70
      on cell apoptosis was observed using RNA interference silencing HSP70 expression.
      RESULTS: Nimesulide significantly inhibited cell growth in SMMC-7721 cells in a
      time- and concentration-dependent manner,  and induced cell apoptosis in a
      concentration-dependent manner. Moreover,  nimesulide promoted the cleavage of
      caspase-9 and PARP and inhibited the mRNA and protein expression of HSP70.
      Through the specific inhibition on HSP70 gene with siRNA,  cell apoptosis
      increased,  and the apoptosis was enhanced by the cleavage activity of caspase-9
      and PARP. CONCLUSION: Nimesulide could inhibit cell growth and induce apoptosis
      in human hepatocellular carcinoma SMMC-7721 cells via the downregulation of
      HSP70.

PMID- 22980657
TI  - [Construction of eukaryotic plasmid of human GPC3 and expression and purification
      of recombinant GPC3  protein].
AB  - AIM: To obtain enough human glypican-3 (GPC3) protein for structural and
      functional research. METHODS: The full-length cDNA coding for GPC3 was cloned by
      RT-PCR from human fetal hepatocytes. The open reading frame (ORF) of the cDNA
      consists of 1 700 bases,    encoding a mature protein of 556 amino acids. The
      cDNA was inserted into the pPICZ A vector to construct a expression plasmid,   
      named pPICZ A-GPC3. Then the plasmid was transformed into a Pichia pastoris
      strain,    GS115 and the positive strains were screened on the YPD plates with
      Zeocin. The positive strains were further screened on cellulose acetate and
      nitrocellulose membrane with HRP labeled His-tag antibody. The selected strains
      were induced by methanol and the supernatants were analyzed by  SDS-PAGE and
      Western blotting. RESULTS: SDS-PAGE analysis showed an anticipated band on the
      gel that could bind with goatanti-GPC3 antibody. Furthermore,    the strain was
      fermented and the expression level was about 5 mg/L,    and the recombinant GPC3
      protein was purified by cation-exchange chromatography from the fermentation
      supernatant. CONCLUSION: Human GPC3 was expressed successfully in Pichia pastoris
      and purified to obtain the recombinant protein from fermentation supernatant,   
      which made it possible for further structural and functional studies on GPC3.

PMID- 22980658
TI  - [Effects of benzene on S+G2/M cell cycle arrest, apoptosis and oxidative DNA
      damage in human peripheral blood mononuclear cells].
AB  - AIM: To observe and verify the benzene-induced cell cycle arrest and apoptosis in
      human peripheral blood mononuclear cells (PBMCs), and explore its effects on
      oxidative DNA damage. METHODS: PBMCs were isolated, cultivated for 24 h and then
      divided into 4 groups supplemented with alcohol solvent as a control, low, middle
      and high concentration benzene (0.5, 5, 50 MUmol/L), respectively. Another 24 h
      later, we assayed the cell growth arrest by MTT, detected cell cycle and
      apoptosis rate by flow cytometry, the content of reactive oxygen species (ROS) by
      DCFH-DA assay, superoxide dismutase (SOD) activity by xanthine oxidase test,
      malondialdelhde (MDA) content by thiobarbituric acid test, glutathione (GSH)
      content by ELISA, DNA damage by single cell gel electrophoresis (SCGE) technology
      and micronucleus assay. RESULTS: Compared with the control group, benzene
      decreased cell viability (P<0.05) and increased cell apoptosis (P<0.05) in a dose
      dependent manner, along with induction of S phase and G2/M phase arrest (P<0.05).
      Meanwhile, benzene induced the accumulation of intracellular ROS and MDA,
      micronucleus rates, comet rates and comet tail length, which were found dose
      dependent and statistically significant compared to the solvent control (P<0.05).
      The activity of SOD and the contents of GSH decreased significantly (P<0.05).
      CONCLUSION: Benzene can induce cell apoptosis, S+G2/M phase accumulation and
      change of oxidoreduction status in PBMCs, and strengthen the effects of lipid
      peroxidation as well as the DNA damage.

PMID- 22980659
TI  - [Effect of perilipin 1 on chicken preadipocyte lipid accumulation].
AB  - AIM: To explore the effect of perilipin 1 on chicken preadipocyte lipid
      accumulation. METHODS: Firstly, pcDNA3.1-perilipin 1 gene eukaryotic expression
      vector was constructed and transfected into primary cultured chicken
      preadipocytes. Twenty-four hours after transfection, chicken preadipocytes were
      cultured in complete medium with oleate, to induce preadipocyte differentiation.
      Then perilipin 1 was detected by Western blotting; the role of perilipin 1 in
      preadipocyte lipid accumulation was investigated by Oil Red O staining extraction
      assay; the expression levels of other genes (FAS, ACC and ATGL) related to the
      chicken adipocyte lipid metabolism were tested by real-time RT-PCR. RESULTS:
      pcDNA3.1-perilipin 1 gene eukaryotic expression vector upregulated the expression
      of perilipin 1 in the transfected chicken preadipocytes. Over-expression of
      perilipin 1 promoted chicken preadipocyte lipid accumulation, while there was no
      significant change in the expression levels of other chicken lipid metabolism
      related genes (FAS, ACC and ATGL). CONCLUSION: Over-expression of perilipin 1 can
      promote chicken preadipocyte lipid accumulation.

PMID- 22980660
TI  - [Preparation and function of human soluble FcgammaRIIb].
AB  - AIM: To detect the concentration of soluble FcgammaRIIb in blood sera of SLE
      patients and healthy controls,  then to obtain recombinant human soluble
      FcgammaRIIb protein (husFcgammaRIIb) in Escherichia coli (E.coli) and examine its
      binding capability with immune complexes (IC) and its effect on IgM secretion by
      B cells. METHODS: The concentration of husFcgammaRIIb in blood sera of SLE
      patients and healthy controls was detected by ELISA. E.coli BL21,  containing pET
      sFcgammaRIIb,  was stimulated by IPTG to induce husFcgammaRIIb expression,  and
      then husFcgammaRIIb protein was purified by Ni-NTA agarose bead system. The IC
      binding ability of husFcgammaRIIb was detected by ELISA. Furthermore,  B cells
      were sorted by immune magnetic bead from human peripheral blood and challenged by
      different stimulators  under the condition of husFcgammaRIIb or not for 10 d, 
      then the concentration of IgM in supernatant was detected by ELISA. RESULTS: The
      concentration of husFcgammaRIIb in the serum of SLE patients was lower than that
      in the controls (P<0.05). The recombinant husFcgammaRIIb protein was successfully
      expressed and purified with M(r); being 41 500. It could combine with IC and the
      absorption became higher with the increasing concentration of IC. After 10-day
      stimulation on the B cells,  the titer of IgM between SPA and SPA+husFcgammaRIIb
      groups was not significantly different (P>0.05),  and the titer was higher in
      SPA+anti-IgM group than SPA group (P<0.01). Interestingly,  the titer of IgM in
      SPA+husFcgammaRIIb+anti-IgM group was lower than SPA+anti-IgM group (P<0.01), 
      SPA group (P<0.01) and SPA+husFcgammaRIIb group (P<0.01). CONCLUSION: The 
      concentration of husFcgammaRIIb in the serum of SLE patients is lower than that
      in the healthy controls. The recombinant husFcgammaRIIb protein can combine with
      IC and inhibit IgM antibody secretion by B cells.

PMID- 22980661
TI  - [Expression of structural protein VP1 of enterovirus 71 in E.coli and preparation
      of anti-VP1 monoclonal antibodies].
AB  - AIM: To express recombinant structural protein VP1 of enterovirus 71 (EV71) in
      E.coli and prepare anti-VP1 monoclonal antibodies (mAbs). METHODS: With P1 gene
      as a template,    EV71 VP1 gene was amplified by PCR and cloned into the
      expression vector pET-32a(+). After transformation into E.coli TG1,    the
      positive clones were screened and sequenced. The recombinant plasmid was then
      transformed into BLgold (DE3) and the recombinant protein in inclusion bodies was
      induced by IPTG and detected by SDS-PAGE. After the inclusion bodies were
      solubilized with 6 mol/L guanidine hydrochloride,    we purified VP1 protein
      using Ni-NTA affinity chromatography,    and then immunized the mice with it to
      prepare the mAbs against VP1 protein. RESULTS: Recombinant VP1 protein was
      expressed in E.coli. We obtained totally 24 VP1 monoclonal hybridoma cell
      strains,    of which one  was EV71  positive determined by Western blotting  and
      five were  positive for IFA. CONCLUSION: These mAbs are valuable reagents for the
      development  of new vaccines and detection kits for EV71.

PMID- 22980662
TI  - [Expression and purification of mucin 16 and preparation and  characterization of
      anti-mucin 16 monoclonal antibody].
AB  - AIM: To generate monoclonal antibodies (mAbs) against mucin 16 using purified
      recombinant protein of human mucin 16 N terminus with His tag (His-mucin 16N) as
      the antigen. METHODS: Mucin 16 N terminus was cloned into a prokaryotic
      expression vector pET-32. His-mucin 16N was then expressed in E.coli and purified
      by the affinity chromotography. Cell fusion was performed after the BALB/c mice
      were immunized with the purified His-mucin 16N protein. We screened hybridoma
      cell strains producing mAbs against mucin 16. The specificity and titer of the
      antibodies were characterized with ELISA, Western blotting, immunofluorescent and
      immunohistochemical staining. RESULTS: The recombinant protein of His-mucin 16N
      was expressed and purified. A few hybridoma cell strains which could secrete
      specific mAbs against mucin 16 were obtained, and one anti-mucin 16 mAb with good
      specificity and high titer was selected and purified. The isotype of this anti
      mucin 16 mAb was determined as IgG1, which indicated that this anti-mucin 16 mAb
      could be used for ELISA, Western blotting, immunofluorescent and
      immunohistochemical staining. The endogenous expression of mucin 16 in various
      cancer cell lines or tissues was also examined with this anti-mucin 16 antibody
      by Western blotting and other immunoassays. CONCLUSION: The recombinant protein
      of His-mucin 16N was expressed and purified successfully, with which we prepared
      anti-mucin 16 mAb with good specificity and high titer.

PMID- 22980663
TI  - [Expression of SIRT1 in right auricle  tissues  and the relationship with
      oxidative stress in patients with atrial fibrillation].
AB  - AIM: To observe the expression of mammalian sirtuin 1 (SIRT1) in right auricle 
      tissues   in patients presenting with atrial fibrillation (AF) and make clear the
      relationship between SIRT1 expression and oxidative stress. METHODS: A total of
      38 patients with rheumatic heart disease were divided into 2 groups:  AF group
      (AF lasted more than 6 months,  n=25) and SR  (sinus rhythm) group (n=13). The
      expression of SIRT1 in right auricle tissues harvested during heart operations
      was detected by immunohistochemistry. Oxidative stress was estimated by the
      amounts of malondialdehyde (MDA) and metallothionein (MT) and the activity of
      superoxide dismutase (SOD) which were detected using thiobarbituric acid reaction
      (TBA),  enzyme-linked immunosorbent assay (ELISA) and xanthine oxidase assay, 
      respectively. RESULTS: Compared with the SR group,  the expression of SIRT1
      protein in the atrium significantly increased in AF group [P<0.05,  (45.8+/
      4.03)% vs (19.7+/-2.54)%]. In AF group,  MDA was (7.24+/-1.05) nmol/mg,  SOD
      (1034.25+/-84.32) U/mg and MT (7.21+/-1.46) MUg/g,  all being significantly
      higher than those in SR group[P<0.05,  MDA: (3.01+/-0.47) nmol/mg;  SOD: 
      (723.63+/-65.23) U/mg;  MT:  (4.31+/-1.23) MUg/g]. Spearman correlation indicated
      that the expression of SIRT1 had a significantly negative correlation with the
      amounts of MDA and MT and the activity of SOD (P<0.05,  r=-0.447,  -0.521,  
      0.394, respectively). CONCLUSION: The expression of SIRT1 increased in patients
      with AF. SIRT1 maybe effects the AF by means of inhibiting the process of
      oxidative stress.

PMID- 22980664
TI  - [Expression of MCP-1 in the patients of chronic hepatitis B complicated with
      nonalcoholic fatty liver disease].
AB  - AIM: To investigate the expression level of monocyte chemoattractant protein-1
      (MCP-1) in the liver of the patients with chronic hepatitis B (CHB) complicated
      with non-alcoholic fatty liver diseases (NAFLD). METHODS: The study enrolled 21
      CHB with NAFLD patients and 46 CHB without NAFLD patients as the controls. Real
      time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and
      immunohistochemistry (IHC) were applied to detect the expression of MCP-1 at the
      mRNA and protein levels in the liver tissues,  respectively. Non-parametric Mann
      Whitney test was used to analyze the difference between the CHB patients with and
      without NAFLD. RESULTS: The mRNA relative expression level of MCP-1 in CHB+NAFLD
      group was 0.034 (0.024-0.058),  higher than that in the control group 0.016
      (0.012-0.024). The  immunohistochemical score was 8.7+/-2.5 in CHB+NAFLD group
      and 6.2+/-3.5 in the control group. The difference in MCP-1 expression at the
      both protein and mRNA levels was significant statistically between the two groups
      (P<0.01). CONCLUSION: MCP-1 expression level in the liver is higher in CHB with
      NAFLD patients than that in CHB without NAFLD patients.

PMID- 22980665
TI  - [Construction and identification of small interfering RNA expression vector
      targeting ATF-2 gene].
AB  - AIM: To construct an eukaryotic expression vector for RNA interference targeting
      activating transcription factor 2 (ATF-2) gene,  and explore its effect on
      proliferation and apoptosis of  HepG2 cells. METHODS: Two complementary
      oligonucleotides were synthesized based on ATF-2 mRNA sequence. The annealed
      fragment was inserted into the vector PBA-siU6. The recombinant plasmid PBA-siATF
      2 was confirmed by DNA sequencing and transfected into HepG2 cells mediated by
      liposome. After transfection,  ATF-2 protein was detected by Western blotting.
      The cellular growth activity and apoptosis rate were measured by MTT assay and
      flow cytometry,  respectively. RESULTS: Recombinant plasmid expressing siRNA
      targeting ATF-2 gene was confirmed by DNA sequencing. Plasmid transfection down
      regulated the level of ATF-2 protein in HepG2 cells,   which blocked cellular
      growth and induced cell apoptosis. CONCLUSION: The eukaryotic expression vector
      for RNA interference targeting ATF-2 gene was constructed successfully,  which
      inhibits HepG2 cell  proliferation and induces cell apoptosis.

PMID- 22980666
TI  - Discussion.

PMID- 22980667
TI  - Thoracoscopic localization of intraparenchymal pulmonary nodules using direct
      intracavitary thoracoscopic ultrasonography prevents conversion of VATS
      procedures to thoracotomy in selected patients.
AB  - OBJECTIVES: To investigate the feasibility, accuracy, and effect on conversion
      rates of intracavitary video-assisted thoracoscopic surgery ultrasonography (VATS
      US) for localization of difficult to visualize pulmonary nodules. METHODS: The
      study consisted of a prospective cohort of VATS-US for localization of
      intraparenchymal peripheral pulmonary nodules. Patients with pulmonary nodules
      not touching the visceral pleura on the computed tomography scan, who were
      scheduled for VATS wedge resection, were prospectively enrolled. The lobe of
      interest was examined: visually, using finger palpation when possible, and using
      the instrument sliding method. The nodule was then sought using a sterile
      ultrasound transducer. The primary outcome measure was the prevention of
      conversion to thoracotomy or lobectomy secondary to positive VATS-US findings in
      patients with nodules that were not identifiable using standard VATS techniques.
      RESULTS: Four different surgeons performed 45 individual VATS-US procedures
      during a 13-month period. Intracavitary VATS-US was able to detect 43 of 46
      nodules. The sensitivity of VATS-US was 93%, and the positive predictive value
      was 100%. The lung nodules were visualized by thoracoscopic lung examination in
      12 cases (27%), palpable by finger in 18 cases (40%), and palpable using the
      instrument sliding technique in 17 cases (38%). In 20 cases, lung nodules were
      not identifiable using any of the traditional techniques and were identified only
      with VATS-US. VATS-US, therefore, prevented conversion to thoracotomy or
      lobectomy without tissue diagnosis in 43% (20/46) of cases. CONCLUSIONS:
      Intracavitary VATS-US is a real-time, feasible, reliable, and effective method of
      localization of intraparenchymal pulmonary nodules during selected VATS wedge
      resection procedures and can decrease the conversion rates to thoracotomy or
      lobectomy.

PMID- 22980668
TI  - Endoscopic tunneling of HeartMate II left ventricular assist device driveline.

PMID- 22980669
TI  - Six years after repair of a giant ascending aortic aneurysm.

PMID- 22980670
TI  - Solid organ transplant training objectives for residents.
AB  - With the aim of analyzing the current state of the educational objectives in the
      training of medical residents in solid organ transplantation (SOT), we conducted
      a review of the status of the official programs of the specialities involved in
      SOT, focusing particularly on lung transplantation. A survey of medical residents
      was also conducted to allow reflexion about the topic. We obtained 44 surveys
      from 4 University Hospitals with active programs in SOT, mainly from intensive
      care medicine and anesthesiology residents. We detected an important number of
      courses oriented to organ donation but very limited in terms of basic training in
      the management of the immediate postoperative period, principles of
      immunosuppression and updates on immunosuppressive therapy and complications
      (particularly rejection and infection). We also identified that these educational
      aspects should be directed not only to medical residents from specialities with a
      close retation to SOT, but also to all who may at some time have a relation to
      such patients. The use of information and communication techniques (ICTs), on
      line courses and also simulations should be instruments to take into account in
      the biomedical training of medical residents. We conclude that we need a specific
      training program in complications of SOT, as well as fundamental principles in
      immunology and immunosuppressor pharmacology.

PMID- 22980671
TI  - Mohs vs. Madison.

PMID- 22980672
TI  - Problems, solutions and actions: addressing barriers in acute hospital care for
      indigenous Australians and New Zealanders.
AB  - The burden of cardiovascular disease for Indigenous people in Australia and New
      Zealand is high and reflects the failings of our health care system to meet their
      needs. Improving the hospital care for Indigenous people is critical in improving
      health outcomes. This paper provides the results from a facilitated discussion on
      the disparities in acute hospital care and workforce issues. The workshop was
      held in Alice Springs, Australia at the second Cardiac Society of Australia and
      New Zealand (CSANZ) Indigenous Cardiovascular Health Conference. Critical issues
      to be addressed include: addressing systemic racism; reconfiguring models of care
      to address the needs of Indigenous people; cultural competence training for all
      health professionals; increasing participation of Indigenous people in the health
      workforce; improving information systems and facilitating communication across
      the health care sector and with Indigenous communities.

PMID- 22980673
TI  - Docosahexaenoic acid complexed to human albumin in experimental stroke:
      neuroprotective efficacy with a wide therapeutic window.
AB  - BACKGROUND: Docosahexaenoic acid (DHA) complexed to human serum albumin (Alb) is
      neuroprotective after experimental stroke. Here we tested using lower
      concentrations of albumin as part of the complex to achieve neuroprotection. We
      found that lower Alb concentrations extend the therapeutic window of protection
      beyond 5 h after stroke onset. METHODS: Sprague-Dawley rats were received 2 h
      middle cerebral artery occlusion (MCAo). The behavior was evaluated on day 1, 2,
      3 and 7 after MCAo. In the dose-response study, animals were given either DHA
      (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg + 0.32, 0.63 or 1.25 g/kg) or saline,
      i.v. 3 h after onset of stroke (n=6-8 per group). In the therapeutic window
      study, DHA-Alb (5mg/kg + 1.25g/kg) was administered i.v. at either 3, 4, 5, 6 or
      7 h after onset of stroke (n=7-9 per group). Alb (1.25g/kg) was given at 3 h or 5
      h and saline at 3h after onset of reperfusion. Seven days after MCAo, infarct
      volumes and number of GFAP, ED-1, NeuN, SMI-71 positive cells and vessels were
      counted. RESULTS: Moderate DHA-Alb doses (0.63 and 1.25 g/kg) improved
      neurological scores compared to albumin-treated rats on days 1, 2, 3 and 7. All
      DHA-Alb doses (0.32, 0.63 and 1.25 g/kg) markedly reduced cortical (by 65-70%),
      striatal (by 52-63%) and total infarct volumes (by 60-64%) compared to native Alb
      group. In the therapeutic window study DHA-Alb led to improved neurological score
      and significant reductions of infarct volumes (especially in the cortical or
      penumbral region), even when treatment was initiated as late as 7 hours after
      onset of MCAo. CONCLUSIONS: The DHA-Alb complex affords high-grade
      neurobehavioral neuroprotection in focal cerebral ischemia, equaling or exceeding
      that afforded by native Alb or DHA, at considerably moderate doses. It has a
      broad therapeutic window extending to 7 h after stroke onset. Taken together,
      these finding support the potential clinical feasibility of administering DHA-Alb
      therapy to patients with acute ischemic stroke.

PMID- 22980674
TI  - Separating intentional inhibition of prepotent responses and resistance to
      proactive interference in alcohol-dependent individuals.
AB  - BACKGROUND: Impulsivity is a hallmark of addictive behaviors. Addicts' weakened
      inhibition of irrelevant prepotent responses is commonly thought to explain this
      association. However, inhibition is not a unitary mechanism. This study
      investigated the efficiency of overcoming competition due to irrelevant responses
      (i.e., inhibition of a prepotent response) and overcoming competition in memory
      (i.e., resistance to proactive interference) in sober and recently detoxified
      alcohol-dependent individuals. METHODS: Three cognitive tasks assessing the
      inhibition of a prepotent response (Hayling task, anti-saccade task and Stroop
      task) and two tasks tapping into the capacity to resist proactive interference
      (cued recall, Brown-Peterson variant) were administered to 30 non-amnesic
      recently detoxified alcohol-dependent individuals and 30 matched healthy
      participants without alcohol dependency. In addition, possible confounds such as
      verbal updating in working memory was assessed. RESULTS: Alcohol-dependent
      subjects performed worse than healthy participants on the three cognitive tasks
      assessing the inhibition of irrelevant prepotent responses but group performance
      was similar in the tasks assessing overcoming proactive interference in memory,
      updating of working memory and abstract reasoning. CONCLUSIONS: These findings
      suggest that alcohol-dependence is mainly associated with impaired capacity to
      intentionally suppress irrelevant prepotent response information. Control of
      proactive interference from memory is preserved. Theoretical and clinical
      implications are discussed.

PMID- 22980675
TI  - Stability of scores and correlations with drinking behaviors over 15 years for
      the Self-Report of the Effects of Alcohol Questionnaire.
AB  - BACKGROUND: The low level of response (LR) to alcohol is an endophenotype that
      predicts future heavy drinking and alcohol use disorders (AUDs). LR can be
      measured by laboratory-based alcohol challenges or by the retrospective Self
      Report of the Effects of Alcohol (SRE) questionnaire. This paper reports the
      relationships among these two measures and how each related to both recent and
      future drinking quantities and problems across 15 years in 235 men. METHODS:
      Probands from the San Diego Prospective Study (SDPS) participated in alcohol
      challenges to determine their LR at age 20, and subsequently at ages 35, 40, 45
      and 50 filled out an SRE regarding the number of standard drinks needed for up to
      four effects early in life (SRE5) and across early, recent, and heaviest drinking
      life epochs (SRET). Changes in SRE scores across time were evaluated with ANOVAs
      and Pearson correlations were used to evaluate how SRE5, SRET and earlier alcohol
      challenge-based LRs related to prior five-year drinking histories and future
      alcohol involvement. RESULTS: While SRE scores decreased 9% over the 15 years,
      the relationships between SRE values with prior five-year drinking parameters and
      with future alcohol intake and problems remained robust, and even improved with
      advancing age. A similar pattern was seen for correlations between SRE and
      alcohol challenge-based LRs 15-30 years previously. CONCLUSIONS: Alcohol
      challenge and SRE-based LRs related to each other, to alcohol use patterns, and
      to future alcohol problems across age 35-50 in the men studied here.

PMID- 22980677
TI  - Evidence-based practice: management of adult sensorineural hearing loss.
AB  - Sensorineural hearing loss is a complex disease state influenced by genetics,
      age, noise, and many other factors. This article reviews our current knowledge
      regarding the causes of sensorineural hearing loss and reviews the more
      challenging clinical presentations of sensorineural hearing loss. We have
      reviewed the latest medical literature in an attempt to provide an evidence-based
      strategy for the assessment and management of sudden sensorineural hearing loss,
      rapidly progressive sensorineural hearing loss, and asymmetric/unilateral
      sensorineural hearing loss.

PMID- 22980676
TI  - Evidence-based practice: management of vertigo.
AB  - The article focuses on the evidence basis for the management of benign paroxysmal
      positional vertigo, the most common diagnosis of vertigo in both primary care and
      subspecialty settings. An overview is presented, along with evidence-based
      clinical assessment, diagnosis, and management. Summaries of differential
      diagnosis of vertigo and outcomes are presented.

PMID- 22980678
TI  - Cochlear implants: clinical and societal outcomes.
AB  - Over the past 30 years, hearing care clinicians have increasingly relied on
      cochlear implants to restore auditory sensitivity in selected patients with
      advanced sensorineural hearing loss. This article examines the impact of
      intervention with cochlear implantation in children and adults. The authors
      report a range of clinic-based results and patient-based outcomes reflected in
      the reported literature on cochlear implants. The authors describe the basic
      assessment of the physiologic response to auditory nerve stimulation; measures of
      receptive and productive benefit; and surveys of life effects as reflected
      measures of quality of life, educational attainment, and economic impact.

PMID- 22980679
TI  - Evidence-based practice: reflux in sinusitis.
AB  - It is now widely recognized that extraesophageal reflux (reflux reaching
      structures above the upper esophageal sphincter) has a wide range of effects on
      the upper aerodigestive tract, as well as the lungs. The degree to which this
      reflux contributes to the pathophysiology of sinusitis and other sinonasal
      diseases is still not completely clear, but an increasing body of literature
      supports a potential role.

PMID- 22980680
TI  - Evidence-based practice: balloon catheter dilation in rhinology.
AB  - Balloon catheter dilation (BCD) is a treatment paradigm for surgical management
      of paranasal sinus inflammatory disease. There are few robust clinical trials
      evaluating the efficacy of balloon technology in chronic rhinosinusitis (CRS).
      The available database largely comprises retrospective, uncontrolled studies with
      insufficiently characterized patient cohorts and a lack of comparator groups.
      Thus, the current evidence base is unable to elucidate the role and indications
      for BCD in the management of medically refractory CRS. Future studies should
      include selected control groups, preferably with randomization and validated
      outcome measures, to determine the efficacy of balloon technology compared with
      endoscopic sinus surgery.

PMID- 22980681
TI  - Epistaxis: a contemporary evidence based approach.
AB  - This article provides a contemporary management protocol for adult epistaxis
      admissions, evidence based where possible, and otherwise based on the authors'
      own experience.

PMID- 22980682
TI  - Evidence-based practice: postoperative care in endoscopic sinus surgery.
AB  - Postoperative care following endoscopic sinus surgery (ESS) for medically
      refractory chronic rhinosinusitis (CRS) is believed to be important to optimize
      clinical outcomes. There is no standardized approach to postoperative care and,
      because of the numerous reported strategies, there remains a debate as to what
      constitutes the optimal postoperative care protocol. This article reviews the
      evidence and describes an evidence-based approach for postoperative care
      following ESS for medically refractory CRS.

PMID- 22980683
TI  - Evidence-based practice: functional rhinoplasty.
AB  - The cause of nasal obstruction can often be attributed to pathologic conditions
      of the nasal valve. The key physical examination finding in nasal valve
      compromise is inspiratory collapse of the nasal sidewall. Validated subjective
      and objective measures evaluating nasal obstruction exist, although with weak
      correlation. Functional rhinoplasty encompasses the surgical techniques used to
      address obstruction occurring in this area. These techniques aim to increase the
      size of the nasal valve opening and/or strengthen the lateral nasal wall and
      nasal ala, preventing dynamic collapse. Much of the supporting evidence for
      functional rhinoplasty consists of observational studies that are universally
      favorable.

PMID- 22980684
TI  - Evidence-based practice: sublingual immunotherapy for allergic rhinitis.
AB  - In this article, the authors review the current evidence regarding the public
      health and economic impact of allergic rhinitis. Diagnostic methods for allergic
      disease are discussed as well as certain nuances of allergy skin testing
      protocols. In addition, the evidence supporting sublingual immunotherapy (SLIT)
      for allergic rhinitis is reviewed, with subsequent attention to certain
      subgroups, such as adults and children, seasonal versus perennial allergens, and
      SLIT efficacy for individual antigens. The authors consider the evidence
      supporting appropriate SLIT dosing as well as the existing data on SLIT safety.

PMID- 22980685
TI  - Evidence-based practice: pediatric obstructive sleep apnea.
AB  - Diagnosis of sleep-disordered breathing (SDB) is most accurately obtained with a
      nocturnal polysomnogram. However, limitations on availability make alternative
      screening tools necessary. Nocturnal oximetry studies or nap polysomnography can
      be useful if positive; however, further testing is necessary to if these tests
      are negative. History and physical examination have insufficient sensitivity and
      specificity for diagnosingpediatric SDB. Adenotonsillectomy remains first-line
      therapy for pediatric SDB and obstructive sleep apnea (OSA). Additional study of
      limited therapies for mild OSA are necessary to determine if these are reasonable
      primary methods of treatment or if they should be reserved for children with
      persistent OSA.

PMID- 22980686
TI  - Evidence-based practice: pediatric tonsillectomy.
AB  - Tonsillectomy is one of the most common surgical procedures performed in children
      in the United States. Indications and recommendations for perioperative
      management are multiple and may vary among clinicians. Although tonsillectomy is
      a safe procedure, it can be associated with morbidity. Several techniques have
      been developed to reduce perioperative complications, but evidence of this
      reduction is lacking. This article provides clinicians with evidence-based
      guidance on perioperative clinical decision making and surgical technique for
      tonsillectomy.

PMID- 22980687
TI  - Evidence-based practice: evaluation and management of unilateral vocal fold
      paralysis.
AB  - This article discusses the causes and symptoms, evaluation, and management of
      unilateral vocal fold paralysis (UVFP). Cross-sectional imaging is appropriate in
      the work-up of idiopathic UVFP, but the routine use of serology is not well
      supported. The usefulness of laryngeal electromyography has remained
      controversial. Predictors of poor prognosis for functionally meaningful recovery
      include fibrillation potentials, positive sharp waves, and absent/reduced
      voluntary motor unit potentials. Voice therapy may be helpful. Injection and
      laryngeal framework surgery (medialization thyroplasty) improve vocal quality.
      The vocal impact of laryngeal reinnervation is comparable with that of
      medialization. Some patients may benefit from multiple procedures.

PMID- 22980688
TI  - Otolaryngology clinic of North America: evidence-based practice: management of
      hoarseness/dysphonia.
AB  - This article reviews the evidence for the evaluation and management for patients
      with dysphonia. The evidence behind laryngoscopy, laryngostroboscopy, laryngeal
      imaging, laryngeal electromyography, and disease-specific questionnaires are
      reviewed. The evidence for management of some of the common conditions leading to
      dysphonia is also reviewed. This article reviews the evidence for voice therapy
      for various voice pathologies; medical management of dysphonia, including
      antibiotics, steroids, and antireflux therapy; and surgical management of glottic
      insufficiency and some benign laryngeal masses.

PMID- 22980689
TI  - Evidence-based practice: endoscopic skull base resection for malignancy.
AB  - Successful outcomes of endoscopic approaches to benign sinonasal tumors have
      launched interest in expanding its use for sinonasal malignancy. Because of the
      heterogeneity and rarity of sinonasal malignancy, evidence for clinical outcomes
      of endoscopic approaches versus traditional craniofacial resection is low. Using
      the Oxford Center for Evidence-based Medicine guidelines, we present the existing
      evidence comparing both techniques for a variety of sinonasal malignancies.

PMID- 22980690
TI  - Evidence-based practice: management of glottic cancer.
AB  - The main issue in the management of glottic squamous cell carcinoma, as for all
      cancers, is adequate disease control while optimizing functional outcomes and
      minimizing morbidity. This is true for early-stage disease as for advanced
      tumors. This article evaluates the current evidence for the diagnostic and
      pretherapeutic workup for glottic squamous cell carcinoma and the evidence
      concerning different treatment options for glottic carcinoma, from early-stage to
      advanced-stage disease.

PMID- 22980691
TI  - Management of well-differentiated thyroid cancer.
AB  - This review provides an overview of current guideline recommendations for the
      clinical evaluation and surgical management of well-differentiated thyroid
      cancer, and further examines the evidence for controversial topics such as the
      minimum degree of primary resection, the role of elective central neck
      dissection, and the extent of lateral neck dissection. Well-differentiated
      thyroid cancer comprises the majority of thyroid cancers, about 90%, and includes
      both papillary and follicular carcinomas. Despite convergence of the medical
      community in establishing treatment guidelines under the American Thyroid
      Association, there still remain many areas of disagreement.

PMID- 22980692
TI  - Evidence-based practice: management of the clinical node-negative neck in early
      stage oral cavity squamous cell carcinoma.
AB  - This article provides a critical review of the evidence surrounding the
      management of the clinical node-negative patient with early-stage oral cavity
      squamous cell carcinoma.

PMID- 22980693
TI  - Clinical decision-making based on evidence.

PMID- 22980694
TI  - The evolution of early awareness and alert methods and systems.

PMID- 22980695
TI  - Health technology reassessment: scope, methodology, & language.

PMID- 22980696
TI  - Engaging clinicians in evidence-based disinvestment: role and perceptions of
      evidence.
AB  - OBJECTIVES: The aim of this study was to determine how evidence from systematic
      review (SR) is perceived and negotiated by expert stakeholders in considering a
      technology for potential disinvestment. METHODS: An evidence-informed stakeholder
      engagement examined results from a diagnostic accuracy SR of vitamin B12 and
      folate tests. Pathologists deliberated around the SR findings to generate an
      informed contribution to future policy for the funding of B12 and folate tests.
      Deliberations were transcribed and subject to qualitative analysis. RESULTS:
      Pathologists did not engage with findings from the SR in depth; rather they
      sought to contest the terms of the problem driving the review and attempted to
      reframe it. Pathologists questioned the usefulness of SR outcomes given the
      variable definitions of B12 deficiency and deferred addressing disinvestment
      options specifically pertaining to B12 testing. However, folate testing was
      proffered as a potential disinvestment candidate, based upon pathologists'
      definition of "appropriate" evidence beyond the bounds of the SR. CONCLUSIONS:
      The value of SR to informing disinvestment deliberations by expert stakeholders
      may be a function of timing as well as content. Engagement of stakeholders in co
      produced evidence may be required at two levels: (i) Early in the synthesis phase
      to help shape the SR and harmonize expert views with the available evidence
      (including gaps); (ii) Collaboration in primary research to fill evidence-gaps
      thus supporting evidence-based disinvestment. Without this, information asymmetry
      between clinically engaged experts and decision makers may preclude the
      collaborative, informed, and technical discussions required to generate
      productive policy change.

PMID- 22980697
TI  - Health technology reassessment of non-drug technologies: current practices.
AB  - OBJECTIVES: Obsolescence is a natural phase of the lifecycle of health
      technologies. Given increasing cost of health expenditures worldwide, health
      organizations have little choice but to engage in health technology reassessment
      (HTR); a structured, evidence-based assessment of the medical, social, ethical,
      and economic effects of a technology, currently used within the healthcare
      system, to inform optimal use of that technology in comparison to its
      alternatives. This research was completed to identify and summarize international
      HTR initiatives for non-drug technologies. METHODS: A systematic review was
      performed using the terms disinvestment, obsolescence, obsolete technology,
      ineffective, reassessment, reinvestment, reallocation, program budgeting, and
      marginal analysis to search PubMED, MEDLINE, EMBASE, and CINAHL until November
      2011. Websites of organizations listed as members of INAHTA and HTAi were hand
      searched for gray literature. Documents were excluded if they were unavailable in
      English, if the title/abstract was irrelevant to HTR, and/or if the document made
      no mention of current practices. All citations were screened in duplicate with
      disagreements resolved by consensus. RESULTS: Sixty full-text documents were
      reviewed and forty were included. One model for reassessment was identified;
      however, it has never been put into practice. Eight countries have some evidence
      of past or current work related to reassessment; seven have shown evidence of
      continued work in HTR. There is negligible focus on monitoring and
      implementation. CONCLUSIONS: HTR is in its infancy. Although health technology
      reassessments are being conducted, there is no standardized approach. Future work
      should focus on developing and piloting a comprehensive methodology for
      completing HTR.

PMID- 22980698
TI  - Cost-effectiveness of exercise programs in type 2 diabetes.
AB  - BACKGROUND: A randomized controlled trial has shown that supervised, facility
      based exercise training is effective in improving glycemic control in type 2
      diabetes. However, these programs are associated with additional costs. This
      analysis assessed the cost-effectiveness of such programs. METHODS: Analysis used
      data from the Diabetes Aerobic and Resistance Exercise (DARE) clinical trial
      which compared three different exercise programs (resistance, aerobic or a
      combination of both) of 6 months duration with a control group (no exercise
      program). Clinical outcomes at 6 months were entered for individual patients into
      the UKPDS economic model for type 2 diabetes adapted for the Canadian context.
      From this, expected life-years, quality-adjusted life-years (QALYs) and costs
      were estimated for all patients within the trial. RESULTS: The combined exercise
      program was the most expensive ($40,050) followed by the aerobic program
      ($39,250), the resistance program ($38,300) and no program ($31,075). QALYs were
      highest for combined (8.94), followed by aerobic (8.77), resistance (8.73) and no
      program (8.70). The incremental cost per QALY gained for the combined exercise
      program was $4,792 compared with aerobic alone, $8,570 compared with resistance
      alone, and $37,872 compared with no program. The combined exercise program
      remained cost-effective for all scenarios considered within sensitivity analysis.
      CONCLUSIONS: A program providing training in both resistance and aerobic exercise
      was the most cost-effective of the alternatives compared. Based on previous
      funding decisions, exercise training for individuals with diabetes can be
      considered an efficient use of resources.

PMID- 22980699
TI  - Order sets in health care: a systematic review of their effects.
AB  - OBJECTIVES: Order sets are widely used in hospitals to enter diagnosis and
      treatment orders. To determine the effectiveness of order sets in improving
      guideline adherence, treatment outcomes, processes of care, efficiency, and cost,
      we conducted a systematic review of the literature. METHODS: A comprehensive
      literature search was performed in various databases for studies published
      between January 1, 1990, and April 18, 2009. A total of eighteen studies met
      inclusion criteria. No randomized controlled trials were found. RESULTS: Outcomes
      of the included studies were summarized qualitatively due to variations in study
      population, intervention type, and outcome measures. There were no important
      inconsistencies between the results reported by studies involving different types
      of order sets. While the studies generally suggested positive outcomes, they were
      typically of low quality, with simple before-after designs and other
      methodological limitations. CONCLUSIONS: The benefits of order sets remain
      eminently plausible, but given the paucity of high quality evidence, further
      investigations to formally evaluate the effectiveness of order sets would be
      highly valuable.

PMID- 22980700
TI  - Cost-effectiveness of alemtuzumab for T-cell prolymphocytic leukemia.
AB  - OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of
      alemtuzumab (CAMPATH-1H) compared with conventional chemotherapy in people with T
      cell prolymphocytic leukemia (T-PLL). METHODS: We developed a decision-analytic
      model to assess the costs and benefits of alemtuzumab or conventional therapy
      based on their effects on quality of life of patients. The main outcome was the
      incremental cost-effectiveness ratio incorporating costs per additional quality
      adjusted life-year (QALY) gained over lifetime. Due to the limited data
      available, a large number of assumptions had to be made to construct the cost
      utility model. One-way, multi-way, and probabilistic sensitivity analyses (PSA)
      were conducted to explore the impact of these uncertainties. Expected values of
      perfect information were also calculated for four specific scenarios. RESULTS:
      Depending on different key assumptions made, the PSA suggested distinct
      conclusions using a willingness-to-pay threshold of 30,000 GBP per QALY gained.
      Using this threshold, the probability that alemtuzumab would be cost-effective
      varies from 0 percent to 53 percent for the four modeled scenarios. Population
      expected value of perfect information analysis suggests that resolving the
      parameter uncertainty in the analysis for people with T-PLL in the United Kingdom
      would have considerable value--up to 5.3 million euro. CONCLUSIONS: Alemtuzumab
      appears more likely to be cost-effective if used earlier in the course of T-PLL
      and where it replaces the use of multiple alternative therapies. However, cost
      effectiveness is highly uncertain and future research is clearly justified.
      Nevertheless, our analysis demonstrates the feasibility of considering the cost
      effectiveness of an agent despite the presence of significant uncertainty to
      provide appropriate assessment information to policy makers.

PMID- 22980701
TI  - Romiplostim and eltrombopag for immune thrombocytopenia: methods for indirect
      comparison.
AB  - OBJECTIVES: Immune thrombocytopenia (ITP) causes increased platelet destruction
      and suboptimal platelet production, increasing risk of bleeding. This analysis
      uses a Bayesian metaregression model to indirectly compare effectiveness of the
      thrombopoietin mimetics romiplostim and eltrombopag for increasing platelet
      counts, and contrasts the results with those of non-Bayesian approaches. METHODS:
      Ten databases were searched during 2010. Placebo-controlled trials of 24 weeks'
      duration were included. An indirect comparison was undertaken using Bayesian
      metaregression, which includes all trials in a single model. This was compared
      with previous analyses in which data for each intervention were combined using
      simple pooling, logistic regression or meta-analysis, followed by indirect
      comparison of pooled values using the Bucher method. RESULTS: Two trials of
      romiplostim and one of eltrombopag were included. The indirect evidence suggests
      romiplostim significantly improves overall platelet response compared with
      eltrombopag. Bayesian metaregression gave an odds ratio (OR) for eltrombopag
      versus romiplostim of 0.11 (95 percent credible interval 0.02-0.66); p values and
      Bayesian posterior probabilities ranged from 0.01 to 0.05 for all analyses. There
      was no significant difference in durable platelet response in any of the
      analyses, although the direction of effect favored romiplostim (OR = 0.15; 95
      percent credible interval, 0.01-1.88); p values and Bayesian posterior
      probabilities ranged from 0.08 to 0.40 across analyses. Results were relatively
      consistent between analyses. CONCLUSIONS: Bayesian metaregression generated
      similar results to other indirect comparison methods, and may be considered the
      most robust as it incorporates all data in a single model and accounts
      appropriately for parameter uncertainty.

PMID- 22980702
TI  - The harmonic study: cost-effectiveness evaluation of the use of the ultrasonic
      scalpel in total thyroidectomy.
AB  - BACKGROUND: Total thyroidectomy (TT) can be performed either with the traditional
      technique or using the ultrasound scalpel. Here, the use of the ultrasound
      scalpel is investigated in order to assess cost-effectiveness from an hospital,
      third party payer and societal perspective. METHODS: A randomized controlled
      trial was conducted at the University Hospital A. Gemelli in Rome. Data refer to
      198 patients, randomized to either surgery with the ultrasound scalpel (n = 96)
      or traditional (n = 102) and followed for 3 months after hospital discharge.
      Operation time (OT) and resource consumption were recorded. Main clinical outcome
      investigated was quality of life (evaluated with EQ-5D). RESULTS: A shorter
      operation time (traditional: 76.36 vs ultrasound: 54.16 minutes, p < 0.001) was
      observed. 3 months after surgery, differences in QoL were significant (0.91 vs
      0.84, p = 0.002). Concerning the hospital perspective, ultrasound scalpel allows
      savings of 119 EUR per patient. From a societal perspective, ultrasound scalpel
      is also related to lower medical resource consumption during a 3 month follow-up
      after discharge (traditional: 129.03 EUR vs ultrasound: 107.82 EUR) and lower non
      medical resource utilization (transport/hotels costs traditional:535.51 EUR vs
      ultrasound: 342.77 EUR. No statistical difference was found in productivity
      losses up to 3 months (traditional: 377.71 EUR vs ultrasound: 385.51 EUR).
      CONCLUSION: Allowing an overall saving of 325.36 EUR per patient, Ultrasound
      scalpel should be adopted for TT procedures in the "A.Gemelli" University
      hospital.

PMID- 22980703
TI  - Deus ex machina or e-slave? Public perception of healthcare robotics in the
      German print media.
AB  - OBJECTIVES: The news media plays a central role in providing information
      regarding new medical technologies and exerts an influence on their social
      perception, understanding, and assessments. This study, therefore, analyzes how
      healthcare robotics are portrayed in the German print news media. It examines
      whether the risks and opportunities of new medical technologies are presented in
      a balanced manner and investigates whether or not print media coverage of these
      technologies is affected by science-fiction discourse, in which robots appear
      mostly as a threat to humans. METHODS: Ten years of German print media coverage
      (2000-2010) have been studied by means of systematic, standardized content
      analysis. RESULTS: Reporting focuses predominantly on beneficial advancements in
      medical practice and the advantages of robotics for patients, medical staff, and
      society. The results show that the dominant relationship between robots and
      humans that is transmitted in print media in medical contexts is positive, with
      robots mostly portrayed as assistants, colleagues, or even friends. Only a small
      number of articles report ethical questions and risks. CONCLUSIONS: In contrast
      to science-fiction discourse, the German print media provides a positive picture
      of robotics to the lay public.

PMID- 22980704
TI  - Attitudes and barriers toward mini-HTA in the Danish municipalities.
AB  - BACKGROUND: In 2008 the Danish National Board of Health launched an information
      campaign aimed at introducing mini-HTA as a management and decision support tool
      for the municipalities. Today (January 2012), mini-HTA is still not used
      regularly in the municipalities. AIM: The aim of this study was to evaluate the
      latent attitudes toward mini-HTA among ninety-three participants in five
      voluntary workshops on mini-HTA held in the period of May 2008 to February 2009.
      METHODS: In a questionnaire including three open questions respondents were asked
      to state their perception of what mini-HTA could be used for in the municipality,
      the main barriers for using mini-HTA, and what could make it easier to implement
      mini-HTA. Answers were analyzed qualitatively and quantitatively using binary
      coding and statistical examination of patterns in form of R-factor analysis.
      RESULTS: The four significant latent attitudes were a general acceptance of HTA
      principles, a derived need for a political/managerial decision to use mini-HTA in
      the municipality, worries about barriers in the medium run, and worries about
      barriers in the short run. CONCLUSIONS: A national information campaign to
      support the uptake of mini-HTA in local health-care institutions was insufficient
      in the Danish municipalities and should have been supplemented with a strategy to
      secure local political/managerial willingness to use mini-HTA and the removal of
      short- and medium-term barriers. The implementation of local HTA should not just
      be seen as a question of how to increase the use of evidence in decision-making,
      but as a matter of reforming local decision processes.

PMID- 22980705
TI  - Pre-market clinical evaluations of innovative high-risk medical devices in
      Europe.
AB  - OBJECTIVES: High-quality clinical evidence is most often lacking when novel high
      risk devices enter the European market. At the same time, a randomized controlled
      trial (RCT) is often initiated as a requirement for obtaining market access in
      the US. Should coverage in Europe be postponed until RCT data are available? We
      studied the premarket clinical evaluation of innovative high-risk medical devices
      in Europe compared with the US, and with medicines, where appropriate. METHODS:
      The literature and regulatory documents were checked. Representatives from
      industry, Competent Authorities, Notified Bodies, Ethics Committees, and HTA
      agencies were consulted. We also discuss patient safety and the transparency of
      information. RESULTS: In contrast to the US, there is no requirement in Europe to
      demonstrate the clinical efficacy of high-risk devices in the premarket phase.
      Patients in Europe can thus have earlier access to a potentially lifesaving
      device, but at the risk of insufficiently documented efficacy and safety.
      Variations in the stringency of clinical reviews, both at the level of Notified
      Bodies and Competent Authorities, do not guarantee patient safety. We tried to
      document the design of premarket trials in Europe and number of patients exposed,
      but failed as this information is not made public. Furthermore, the Helsinki
      Declaration is not followed with respect to the registration and publication of
      premarket trials. CONCLUSIONS: For innovative high-risk devices, new EU
      legislation should require the premarket demonstration of clinical efficacy and
      safety, using an RCT if possible, and a transparent clinical review, preferably
      centralized.

PMID- 22980706
TI  - Post-introduction observation of healthcare technologies after coverage: the
      Spanish proposal.
AB  - OBJECTIVES: When a new health technology has been approved by a health system, it
      is difficult to guarantee that it is going to be efficiently adopted, adequately
      used, and that effectiveness, safety, and consumption of resources and costs are
      in line with what was expected in preliminary investigations. Many governmental
      institutions promote the idea that efficient mechanisms should be established
      aimed at developing and incorporating continuous evidence into health
      technologies management. The purpose of this article is to stimulate the
      discussion on systematic post-introduction observation of health technologies.
      METHODS: Literature review and input of HTA experts. RESULTS: The study addresses
      the key issues related to post-introduction observation and presents a summary of
      the guide commissioned by the Spanish Ministry of Health, Social Policy and
      Equality to the Galician HTA agency for the prioritization and implementation of
      systematic post-introduction observation in Spain. The manuscript describes the
      prioritization tool developed as part of this project and discusses the main
      aspects of protocol development, observation implementation, and assessment of
      results. CONCLUSIONS: The observation of prioritized health technologies after
      they are introduced in standard clinical practice can provide useful information
      for health organizations. However, implementing the observation of health
      technologies can require specific policy frameworks, commitment from different
      stakeholders, and dedicated funding.

PMID- 22980707
TI  - Strengthening the health system to enhance mental health in Zambia: a policy
      brief.
AB  - BACKGROUND: Mental illness constitutes a large proportion of the burden of
      disease in Zambia. Yet mental health services at the primary care level are
      either provided in a fragmented manner or are lacking altogether. METHODS: A
      literature review focused on terms including mental health and primary care and
      strategic options were analyzed. RESULTS: From the analysis, two options were
      considered for integrating mental health into primary health care. An incremental
      option would start with a pilot project introducing mental health services into
      primary care with a well-designed evaluation before scaling up. One key advantage
      of this option is that it is possible to make improvements in the plan, if
      needed, before scaling up. A comprehensive option would entail introducing mental
      health services into primary care in all nine provinces of Zambia. In this
      option, scaling up could occur more rapidly than an incremental approach.
      CONCLUSIONS: Strategies to implement either option must address several barriers,
      including insufficient funding for mental health services, inadequate mental
      health indicators, lack of general public awareness of and social stigma attached
      to mental illnesses and mental health care not being perceived as cost-effective
      or affordable.

PMID- 22980708
TI  - Early awareness and alert systems: an overview of EuroScan methods.
AB  - OBJECTIVES: Early awareness and alert (EAA) activities are increasingly
      recognized to be an important component of the health technology assessment (HTA)
      process. Sharing information on methods used in this discipline is vital to
      ensure the development of sustainable systems. The objectives of this study is to
      outline the approach taken to share the different methods that members of the
      EuroScan International Network use by producing a methods toolkit; and to provide
      an overview of the similarities and differences in methods adopted by EAA
      systems. METHODS: A Delphi technique was used to develop the methods toolkit.
      Structured questionnaires were used to identify the sources used in the
      identification of emerging technologies and to determine the methods used by
      agencies to carry out EAA activities. RESULTS: A methods toolkit incorporating
      guidance on all of the stages described by EuroScan members was produced. The
      toolkit and an accompanying checklist presents users with different methods that
      can be adopted to suit their needs. The comparative analysis demonstrates that
      different methods are being used by EAA systems dependent on resources available
      and customer requirements. Differences in identification, filtration,
      prioritization, and assessment are apparent along with the role of collaborators
      in these processes. CONCLUSIONS: The methods used by EAA systems are not
      homogeneous resulting in a toolkit constructed on the basis of "one size doesn't
      fit all." Methods in this discipline are developing continually to accommodate
      changes in health systems and the HTA world. Differences between agencies and the
      sharing of ideas and experiences enable EAA agencies to adapt to these
      developments.

PMID- 22980709
TI  - Analyzing 10 years of early awareness and alert activity in the United kingdom.
AB  - OBJECTIVES: The aim of this study was to assess the accuracy of the English
      National Horizon Scanning Centre (NHSC) in identifying and filtering
      pharmaceutical developments using end user and international collaborator
      databases of emerging technologies as proxies for new drugs of likely
      significance to health services and/or patients. METHODS: We used the NHSC
      information system and the list of National Institute for Health and Clinical
      Excellence (NICE) technology appraisals to estimate the false positive rate for
      NHSC identification, filtration, and reporting. We assessed the sensitivity of
      NHSC identification and filtration of pharmaceuticals for NICE technology
      appraisals from 1999 to the end of December 2010, and for pharmaceuticals entered
      into the EuroScan International Network database. RESULTS: We estimate that
      overall NHSC identification, filtration and reporting had a positive predictive
      value of 0.39 (95 percent CI, 0.36 to 0.43) and a false positive rate of 60
      percent. Using NICE appraisals and EuroScan's database as proxies for
      pharmaceuticals of significance, we estimate the NHSC sensitivity over the 10
      year period at 0.92 (95 percent CI, 0.89 to 0.95) and 0.89 (95 percent CI, 0.82
      to 0.96) respectively. CONCLUSIONS: Our results suggest that the NHSC has
      performed well in terms of sensitivity over the past decade, but that the false
      positive rate of 60 percent may indicate that the filtration criteria for
      pharmaceuticals could be tightened for increased efficiency. Future evaluations
      of EAA systems should include an element of external review and explore the level
      of accuracy acceptable to funders and customers of such systems.

PMID- 22980710
TI  - Early awareness and alert activities in Latin America: current situation in four
      countries.
AB  - OBJECTIVES: The aim of this study was to briefly describe the current state of
      early awareness and alert (EAA) activities and systems in four Latin-American
      countries (Argentina, Brazil, Colombia, and Mexico). METHODS: Key informants were
      selected and completed an open questionnaire that included the following domains:
      current state of EAA activities and systems in each country, potential role for
      EAA systems in the health system, and future EAA projects that are currently
      being considered. RESULTS: In all four countries, health technology assessment
      (HTA) processes are used to prioritize the use of health resources, albeit at
      varying degrees and with different mechanisms and methodologies. EAA activities
      are still limited and there are virtually no institutions or units with specific
      functions explicitly devoted to EAA activity. However, most countries have
      developed some initial forms of EAA systems. Being in its initial stages there is
      no clear differentiation between these early awareness activities and other HTA
      functions, and no specific methodologies or processes are used to anticipate the
      emergence of new technologies. Consequently, early evaluation of technologies
      generally occurs in a reactive manner, after they have been introduced in the
      market and under the pressure of different stakeholders. CONCLUSIONS: There is
      growing awareness that the early identification and assessment of emerging
      technologies should be an integral part of HTA and the decision-making process.
      Many initiatives are currently focusing on building partnerships between the
      various regulatory bodies involved in the incorporation of technologies at
      national levels. It is reasonable to foresee that EAA activities will continue to
      develop and expand in the region.

PMID- 22980711
TI  - Implementing a national early awareness and alert system for new and emerging
      health technologies in Italy: the COTE Project.
AB  - OBJECTIVES: The aim of this study was to establish a national Early Awareness and
      Alert (EAA) system for the identification and assessment of new and emerging
      health technologies in Italy. METHODS: In 2008, Agenas, a public body supporting
      Regions and the Ministry of Health (MoH) in health services research, started a
      project named COTE (Observatory of New and Emerging Health Technologies) with the
      ultimate aim of implementing a national EAA system. The COTE project involved all
      stakeholders (MoH, Regions, Industry, Universities, technical government bodies,
      and Scientific Societies), in defining the key characteristics and methods of the
      EAA system. Agreement with stakeholders was reached using three separate
      workshops. RESULTS: During the workshops, participants shared and agreed methods
      for identification of new and emerging health technologies, prioritization, and
      assessment. The structure of the Horizon Scanning (HS) reports was discussed and
      defined. The main channels for dissemination of outputs were identified as the
      EuroScan database, and the stakeholders' Web portals. During the final workshop,
      Agenas presented the first three HS reports produced at national level and
      proposed the establishment of a permanent national EAA system. CONCLUSIONS: The
      COTE Project created the basis for a permanent national EAA system in Italy. An
      infrastructure to enable the stakeholders network to grow was created, methods to
      submit new and emerging health technologies for possible evaluation were
      established, methods for assessment of the technologies selected were defined,
      and the stakeholders involvement was delineated (in the identification,
      assessment, and dissemination stages).

PMID- 22980712
TI  - Scanning the horizon in a decentralized healthcare system: the Canadian
      experience.
AB  - Canada has a highly decentralized health care system with 13 provinces and
      territories delivering health care within their own respective jurisdictions.
      Decisions regarding which innovative health technologies to adopt are often
      driven by the unique health care priorities of each jurisdiction's population. To
      understand these needs, the Canadian Agency for Drugs and Technologies in
      Health's (CADTH's) Early Awareness Service has expanded its activities. In
      addition to proactively scanning the horizon for new and emerging health
      technologies, the Early Awareness Service also scans the horizon for national and
      jurisdictional health policy issues. This paper looks at CADTH's process for
      identifying and monitoring policy issues at a national and jurisdictional level.
      CADTH's Early Awareness Service delivers timely information on emerging health
      care concerns and technologies that may affect health care finances, facilities,
      operations, and patient care. The identification of important policy issues can
      help determine which new and emerging technologies will have the most significant
      impact on the health care system. The information that CADTH scans can also be
      used to help decision-makers prepare for potential developments and events that
      may have an impact on health care systems. By improving its capability to
      identify and share policy issues across and within jurisdictions, CADTH is better
      situated to provide information that can be used by policy-makers to help them
      plan and anticipate for the introduction of new technologies and future
      developments affecting the unique health care needs of their jurisdictions.

PMID- 22980713
TI  - Early awareness and alert systems for medical technologies in Israel.
AB  - BACKGROUND: Throughout the world, decision makers face the need to plan on the
      basis of uncertainty. Prospective updates on future trends of medical technology
      usage are tools to improve national health status. In Israel, this challenge is
      met by several steps taken to promote insight into the realm of emerging
      technologies. Israel's unique horizon strategy refers to three time spans: the
      immediate to short-term (for the coming year) updating the National List of
      Health Services (NLHS) and quarterly scanning; the medium-term (3 years to a
      decade) revitalizing hospital devices and infrastructure; and long-term planning
      (over a decade), such as the "Health Israel 2020 Project". METHODS: A description
      of the Israeli setup of different time spans and tiers. RESULTS: The matrix of
      players, loci, interests, population groups, and incentives creates a complex
      situation and the Ministry of Health has to regulate the different suppliers and
      tiers of insurance (obligatory, supplementary, and private), balancing need,
      equity, and cost containment in preparing for future health care. However,
      preparedness is not a sterile laboratory and is pervaded by numerous dilemmas and
      the search for adequate evidence for new less mature technologies is an on-going
      challenge. CONCLUSION: Bridging the forecasting chasm for the future requires
      analyzing needs, reinforcing evidence and seeing "around the corner" when
      synergizing between all the "actors" in the national arena. Expert consultation
      and international cooperation with similar horizon organizations can assist in
      paving the way for more successful planning efforts for future medical technology
      implementation.

PMID- 22980714
TI  - Using best-worst scaling in horizon scanning for hepatocellular carcinoma
      technologies.
AB  - OBJECTIVES: There is a growing need for efficient procedures for identification
      of emerging technologies by horizon scanning systems. We demonstrate the value of
      best-worst scaling (BWS) in exploring clinicians' views on emerging technologies
      that will impact outcomes in hepatocellular carcinoma (HCC) in the next 5 to 10
      years. METHODS: Clinicians in Asia, Europe, and the United States were surveyed
      and their views about eleven emerging technologies relevant to HCC were explored
      using BWS (case 1). This involved systematically presenting respondents with
      subsets of five technologies and asking them to identify those that will have the
      most and least impact on HCC within 5 to 10 years. Statistical analysis was based
      on sequential best-worst and analyzed using conditional logistic regression.
      RESULTS: A total of 120 clinicians uniformly distributed across ten countries
      completed the survey (37 percent response rate). Respondents were predominately
      hepatologist (41 percent) who focused on HCC (65 percent) and had national
      influence in this field (39 percent). Respondents viewed molecular targeted
      therapy (p < .001) and early detection of HCC (p < .001) as having most
      potential, while improved surgical techniques (p < .001) and biopsy free HCC
      diagnostics (p < .001) were viewed upon negatively. CONCLUSIONS: We demonstrate
      that BWS could be an important research tool to facilitate horizon scanning and
      HTA more broadly. Our research demonstrates the value of including clinicians'
      preferences as a source of data in horizon scanning, but such methods could be
      used to incorporate the opinions of a broad array of stakeholders, including
      those in advocacy and public policy.

PMID- 22980721
TI  - Environmental lung diseases: clinical and imaging findings.
AB  - Environmental lung diseases are caused by exposure to adverse environmental
      conditions, such as atmospheric pressure changes or the ingestion or inhalation
      of toxic agents. The development of environmental lung diseases depends on the
      intensity and duration of exposure, the physiological and biological
      susceptibility of the host, and the toxic effects of the adverse environmental
      conditions encountered. A combination of clinical features, related exposure
      history, imaging findings, and a review of previous reports that support an
      association between exposure and the disease process is required for diagnosis.

PMID- 22980722
TI  - Recombinant FVIIa concentrate-associated thrombotic events in congenital bleeding
      disorders other than hemophilias.
AB  - Recombinant FVIIa concentrate has been originally used in the treatment of
      hemophilia patients with inhibitors. Recently, its use has been expanded to a
      variety of off-label indications. Thrombosis is the most important side effect.
      This may occur especially in off-label use  but also in hemophiliacs with
      inhibitors. The present study investigated the occurrence of thrombosis in
      congenital bleeding disorders other than hemophilias as gathered from personal
      files and from the literature. Fifteen patients (seven FVII deficiency, one
      fibrinogen defect, four FXI deficiency,  one von Willebrand disease, and two
      Glanzmann's Thrombasthenia) have been evaluated. Thrombosis was arterial in eight
      instances, venous in six, whereas in one case the type of thrombosis was
      unspecified. In eight cases, associated risk factors were present. Two patients
      with FXI deficiency  had inhibitors. Dosage was variable. There was at least one
      fatality but in five cases evolution was not reported. The remaining patients
      recovered with variable sequels.

PMID- 22980723
TI  - Endothelial cell loss: Biaxial small-incision torsional phacoemulsification
      versus biaxial small-incision longitudinal phacoemulsification.
AB  - PURPOSE: To compare clinical results of biaxial small-incision torsional
      phacoemulsification and biaxial small-incision longitudinal phacoemulsification.
      SETTING: Department of Ophthalmology, School of Medicine, Namik Kemal University,
      Tekirdag, Turkey. DESIGN: Randomized controlled clinical trial. METHODS: Eyes
      with high-density nuclear cataract were assigned to have biaxial longitudinal
      (microburst mode) or biaxial torsional phacoemulsification. The main outcomes
      included corrected distance visual acuity (CDVA), central corneal thickness
      (CCT), central endothelial cell density (ECD), total ultrasound time (UST),
      cumulative dissipated energy (CDE), percentage total equivalent power in position
      3, and balanced salt solution volume. Postoperative follow-up was at 1 day, 1
      week, and 1 and 3 months. RESULTS: Each group comprised 35 patients (35 eyes).
      Three months postoperatively, the mean CDVA for each group was 0.02 logMAR and
      the mean CCT returned to the preoperative level (P=.589 and P=.554,
      respectively). During the postoperative follow-up, the percentage of mean
      endothelial cell loss in both groups was between 35.4% and 39.1%; there was no
      statistically significant difference between the groups (P>.05). The mean CDE,
      UST, percentage total equivalent power in position 3, and balanced salt solution
      volume values were similar in the 2 groups (P>.05). CONCLUSION: The risk for high
      endothelial cell loss should be considered when the phacoemulsification of high
      density nuclear cataracts is performed using either method. FINANCIAL DISCLOSURE:
      No author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 22980724
TI  - Using multiple trabecular micro-bypass stents in cataract patients to treat open
      angle glaucoma.
AB  - PURPOSE: To evaluate the efficacy of multiple trabecular micro-bypass stents
      combined with cataract surgery in patients with open-angle glaucoma (OAG) and
      cataract. SETTING: Private practice, Mississauga, Ontario, Canada. DESIGN:
      Comparative case series. METHODS: Eyes with OAG had implantation of 2 or 3 micro
      bypass stents with concurrent cataract surgery and follow-up through 1 year.
      Efficacy measures were intraocular pressure (IOP) and topical ocular hypotensive
      medication use. Safety assessment included complications and corrected distance
      visual acuity (CDVA). RESULTS: The study comprised 53 eyes (47 patients); 28 had
      implantation of 2 stents and 25 had implantation of 3 stents. The overall mean 1
      year postoperative IOP was 14.3 mm Hg, which was significantly lower than
      preoperative IOP overall and in each group (P<.001). The target IOP was achieved
      in a significantly higher proportion of eyes at 1 year versus preoperatively (77%
      versus 43%; P<.001). Overall, 83% of eyes had a decrease in topical ocular
      hypotensive medication at 1 year from preoperatively, with a 74% decrease in the
      mean number of medications (from 2.7 to 0.7) at 1 year (P<.001). The 3-stent
      group was on significantly fewer medications than the 2-stent group at 1 year
      (0.4 versus 1.0; P=.04). CONCLUSIONS: Using multiple micro-bypass stents with
      concurrent cataract surgery led to a mean postoperative IOP of less than 15 mm Hg
      and allowed patients to achieve target pressure control with significantly fewer
      medications through 1 year. FINANCIAL DISCLOSURE: Dr. Ahmed is a consultant to
      Glaukos Corp. No other author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 22980725
TI  - Childhood cancer: incidence and early deaths in Argentina, 2000-2008.
AB  - INTRODUCTION: Knowledge on the epidemiology of childhood cancer in Latin America
      is limited. The Argentinean Oncopaediatric Registry (ROHA) has been active since
      2000. Data for 2000-2008 are described in the present work. MATERIALS AND
      METHODS: ROHA is fed from a network of paediatric units and population-based
      cancer registries. Cases are coded by the International Classification of
      Childhood Cancer. RESULTS: A total of 11447 children aged 0-14 diagnosed with
      cancer were reported. Histologically verified cases and cases identified only
      through death certificates were respectively 91% and 6%. The annual age of
      standardised incidence rate of all cancers was 128.5 per million. Proportions of
      leukaemia's, lymphoma's and Central Nervous System tumours were 37%, 13% and 18%.
      The distribution of rates of acute lymphatic leukaemia by the year of age showed
      a peak around age 3. Eighty percent of the patients are treated in public
      hospital and around 35% migrate for some of the treatment. Deaths within a month
      of diagnosis were 5% in 2000 and 3% in 2008. CONCLUSIONS: Childhood cancer
      incidence in Argentina is somewhat lower than in North American and in Western
      European countries: the deficit is mainly due to tumours of the Central Nervous
      system and other solid tumours. Childhood cancer incidence did not show any
      tendency to increase. The possible excess of Hodgkin lymphoma in the Northeast
      region requires additional studies. Early deaths after diagnosis indicate an
      unsatisfactory state of the overall organisation of childhood cancer care. Data
      from ROHA are used for decision making at local and national levels.

PMID- 22980726
TI  - Dissociated responses to newer antimyeloma drugs identify a subset of refractory
      patients with an extremely poor prognosis.
AB  - We describe the striking and unexpected evolution of 10 patients with de novo
      multiple myeloma treated with novel-agent based induction therapy, who displayed
      a dissociated evolution characterised by an apparent good response contrasting
      with the concomitant development of aggressive non-secreting plasmocytomas
      immediately before, or just after, autologous stem cell transplantation. Patients
      did not respond to salvage therapies. Eight of them died from progression less
      than 12 months after diagnosis. This unusual evolution in the era of novel agents
      warrants further scrutiny.

PMID- 22980727
TI  - The frequency of outdoor play for preschool age children cared for at home-based
      child care settings.
AB  - OBJECTIVE: Given that more than 34% of U.S. children are cared for in home-based
      child care settings and outdoor play is associated with physical activity and
      other health benefits, we sought to characterize the outdoor play frequency of
      preschoolers cared for at home-based child care settings and factors associated
      with outdoor play. METHODS: Cross-sectional study of 1900 preschoolers
      (representing approximately 862,800 children) cared for in home-based child care
      settings (including relative and nonrelative care) using the nationally
      representative Early Childhood Longitudinal Study, Birth Cohort. RESULTS: Only
      50% of home-based child care providers reported taking the child outside to walk
      or play at least once/day. More than one-third of all children did not go outside
      to play daily with either their parent(s) or home-based child care provider.
      There were increased odds of going outside daily for children cared for by
      nonrelatives in the child's home compared with care from a relative. Children
      with >=3 regular playmates had greater odds of being taken outdoors by either the
      parents or child care provider. We did not find statistically significant
      associations between other child level (age, sex, screen-time), family level
      (highest education in household, mother's race, employment, exercise frequency),
      and child care level (hours in care, provider's educational attainment,
      perception of neighborhood safety) factors and frequency of outdoor play.
      CONCLUSIONS: At a national level, the frequency of outdoor play for preschoolers
      cared for in home-based child care settings is suboptimal. Further study and
      efforts to increase outdoor playtime for children in home-based child care
      settings are needed.

PMID- 22980728
TI  - Work experience and style explain variation among pediatricians in the detection
      of children with psychosocial problems.
AB  - OBJECTIVE: To assess whether variation in the proportion of children identified
      as having psychosocial problems by individual preventive pediatricians can be
      explained by pediatrician characteristics, over and above variations in the mix
      of children. Furthermore, to assess whether the characteristics of preventive
      pediatricians were related to the quality of problem identification. METHODS: We
      used data from approximately 3070 children ages 5 to 6 years who were assessed
      during a routine well-child visit by a preventive pediatrician in the Netherlands
      (response rate 85.2%). We obtained data about parent-reported child problems by
      using the Child Behavior Checklist (CBCL), sociodemographic background of the
      family, and characteristics of the preventive pediatrician. After each
      assessment, preventive pediatricians reported whether they had identified any
      psychosocial problem in the child. Multilevel logistic regression analyses were
      used to assess whether variation in the proportion of children identified by
      preventive pediatricians as having a psychosocial problem could be explained by
      the characteristics of preventive pediatricians and whether these characteristics
      were related to the quality of problem identification. RESULTS: Preventive
      pediatricians varied widely in the proportion of children identified as having
      psychosocial problems. Pediatrician characteristics such as work experience and
      work style (for example, on indication use of behavior questionnaires like the
      CBCL in routine care) explained about a quarter of this inter-pediatrician
      variation; child characteristics did not explain this variation even though
      characteristics like gender and parental education level were associated with
      likelihood of problem identification. More use of the CBCL and less use of the
      Teacher Report Form in routine care resulted in a better problem identification
      by preventive pediatricians. Work experience was not related to better problem
      identification. CONCLUSIONS: Preventive pediatricians identify psychosocial
      problems in children in a standardized way, but important inter-pediatrician
      variation remains. This variation may be reduced further and quality improved by
      changing their work style and targeted training.

PMID- 22980729
TI  - Is nonperforated pediatric appendicitis still considered a surgical emergency? A
      survey of pediatric surgeons.
AB  - OBJECTIVE: To describe the beliefs and preferences of pediatric surgeons
      regarding the emergent nature of nonperforated appendicitis. METHODS: An
      electronic mailing was sent to all 1052 members of the American Pediatric
      Surgical Association (APSA) inviting participation in a 26-item survey, which was
      administered by Survey Monkey (www.surveymonkey.com). Chi-square and Mann-Whitney
      tests were used for bivariate analysis. Spearman's rho was used for nonparametric
      correlation. RESULTS: Four hundred eighty-four pediatric surgeons (46%) responded
      to the survey. Few respondents (4%) considered nonperforated appendicitis to be a
      surgical emergency. A minority (14%) would come in from home to perform an
      overnight appendectomy. Most (92%) believe that postponing overnight appendectomy
      until daytime does not result in a clinically significant increase in
      perforation. Respondents endorsed surgeon fatigue (56%) and limited operating
      room availability (56%) most often among factors that would make them more likely
      to postpone surgery. Sixty-eight percent reported no departmental guideline
      regarding delay of overnight appendectomy. CONCLUSIONS: Most pediatric surgeons
      in our study believe nonperforated appendicitis is not a surgical emergency and
      prefer to postpone overnight appendectomy.

PMID- 22980730
TI  - Trespassing cancer cells: 'fingerprinting' invasive protrusions reveals
      metastatic culprits.
AB  - Metastatic cancer cells produce invasive membrane protrusions called invadopodia
      and pseudopodia, which play a central role in driving cancer cell dissemination
      in the body. Malignant cells use these structures to attach to and degrade
      extracellular matrix proteins, generate force for cell locomotion, and to
      penetrate the vasculature. Recent work using unique subcellular fractionation
      methodologies combined with spatial genomic, proteomic, and phosphoproteomic
      profiling has provided insight into the invadopodiome and pseudopodiome signaling
      networks that control the protrusion of invasive membranes. Here I highlight how
      these powerful spatial 'omics' approaches reveal important signatures of
      metastatic cancer cells and possible new therapeutic targets aimed at treating
      metastatic disease.

PMID- 22980731
TI  - Inside-out, outside-in, and inside-outside-in: G protein signaling in integrin
      mediated cell adhesion, spreading, and retraction.
AB  - The integrin family of cell adhesion receptors mediates bi-directional signaling:
      'inside-out' signaling activates the ligand binding function of integrins and
      'outside-in' signaling mediates cellular responses induced by ligand binding to
      integrins leading to cell spreading, retraction, migration, and proliferation.
      Integrin signaling requires both heterotrimeric G proteins and monomeric small G
      proteins. This review focuses on recent development in the roles of G proteins in
      integrin outside-in signaling. The finding of direct interaction between the
      heterotrimeric G protein subunit Galpha13 and integrin beta subunits reveals a
      new mechanism for integrin signaling, and also uncovers a crosstalk between the
      signaling pathways initiated by G protein-coupled receptors (GPCRs) and
      integrins. This crosstalk, which may be referred to as 'inside-outside-in'
      signaling, dynamically regulates contractility and greatly promotes integrin
      outside-in signaling.

PMID- 22980733
TI  - New guidelines for cesarean section on maternal request.

PMID- 22980732
TI  - Solving the lost in translation problem: improving the effectiveness of
      translational research.
AB  - Translational research frequently fails to replicate in the clinic what has been
      demonstrated in the laboratory. This has been true for neuroprotection in the
      central nervous system, neuroprotection in glaucoma, as well as many other areas
      of medicine. Two fundamental reasons for this 'Lost in Translation' problem are
      the 'Butterfly Effect' (chaotic behavior of many animal models) and the 'Two
      Cultures' problem (differences between the methodologies for preclinical and
      clinical research). We propose several strategies to deal with these issues,
      including the use of ensembles of animal models, adding intraocular pressure
      lowering to preclinical neuroprotection studies, changing the way in which
      preclinical research is done, and increasing interactions between the preclinical
      and clinical teams.

PMID- 22980734
TI  - Indications for cesarean section on maternal request--guidelines for counseling
      and treatment.
AB  - AIM: The aim was to find scientific evidence and, based on this, to develop
      national medical guidelines in Sweden for cesarean section on mother's request.
      BACKGROUND: More than 17% of all births in Sweden in 2008 were cesarean sections,
      compared to 5% at the beginning of the 1970s. About 8% of the cesarean sections
      were performed at mother's request. The predominant reason for this preference is
      fear of childbirth. When deciding whether to perform an elective cesarean
      section, the obstetrician must emphasize the long- and short-term health
      consequences for the mother and her baby, as well as weigh the risks associated
      with the procedure itself against not performing the procedure. Clarification is
      needed to determine for which conditions it is appropriate to comply with the
      mother's request. MATERIALS AND METHOD: A literature review was conducted to
      identify factors that were relevant as an argument to meet the request for
      cesarean section on maternal request. The authors analyzed these factors
      individually to determine. FINDINGS: The guidelines suggest that it is
      appropriate to comply with a woman's request for cesarean section if the reason
      for her request is deemed sufficiently serious and if, after participating in a
      counseling program, the woman persists in her request for cesarean section.
      CONCLUSION: A request for cesarean section where no medical indication is present
      should not be met without considerations concerning the safety of the mother and
      her baby, while also weighing the risk of adverse outcomes for mother and baby.

PMID- 22980735
TI  - The hazard of pregnancy loss and stillbirth among women in Kersa, East Ethiopia:
      a follow up study.
AB  - BACKGROUND: Although pregnancy loss causes considerable challenge to women's
      health, population-based studies in rural areas are not widely available in low
      income countries. This study aims to determine the hazard of pregnancy loss and
      related factors in the rural communities of Ethiopia. METHODOLOGY: A prospective
      community-based study was conducted over a period of 1 year. Pregnancy was
      identified as early as possible by a pregnancy urine test. All pregnant women
      identified during the screening were followed up at their home until termination
      of pregnancy or delivery of the neonate. The total follow-up time was 7802
      'pregnant person months'. A Cox regression analysis was done to estimate the
      hazard of pregnancy loss. RESULT: Out of a total of 1438 terminated pregnancies,
      143 (9.9%) did not end in live birth, 116 ended due to bleeding and 27 were
      stillbirths. Whilst the hazard of pregnancy loss was low among women with
      pregnancy interval of two or more years [AHR 0.3 (95%CI: 0.15, 0.43)], it was
      high among women having unplanned pregnancy [AHR 2.2 (95% CI: 1.56, 3.11)], among
      those who complained STI like symptoms during the index pregnancy [AHR 4.5 (95%
      CI: 2.79, 7.38)] and among those never received antenatal care [AHR 1.8 (95% CI:
      1.13, 2.73)]. CONCLUSION: Pregnancy loss was higher amongst women experienced
      unplanned pregnancy, complained STI like symptoms and women who had not attended
      antenatal care services. RECOMMENDATION: To reduce pregnancy loss in rural
      Ethiopia expanding and promoting the use of family planning, antenatal services
      and other reproductive health care is necessary.

PMID- 22980736
TI  - Women's perceptions of fetal movements in full-term pregnancy.
AB  - BACKGROUND: Besides the frequency of the fetal movements the woman's perceptions
      of the movements can give additional information about the unborn baby's
      wellbeing. OBJECTIVE: To explore women's perceptions of fetal movements in full
      term pregnancy. METHODS: Interviews with 40 women in gestational weeks 37 + 2 to
      41 + 5, all with uncomplicated pregnancies. All women were recruited from one
      antenatal clinic in the capital of Sweden. With an inductive approach using a
      content analysis the answers to the question: "Can you describe how your baby has
      moved this week?" was analysed. RESULTS: Fetal movements were categorized into
      seven categories: strong and powerful, large, slow, stretching, from side to
      side, light, and startled. CONCLUSIONS: Almost all the women perceived the fetal
      movements at the end of pregnancy as strong and powerful, and internal pressure.
      Including women's perceptions of fetal movements in the obstetric anamneses,
      gives valuable information about the fetus.

PMID- 22980737
TI  - Young women's experiences of managing self-treatment for anogenital warts.
AB  - OBJECTIVES: The purpose of this study is to explore the experiences of self
      treatment for anogenital warts from the perspective of a group of young women who
      received it. STUDY DESIGN: Ten young Swedish women were interviewed in the study,
      aged between 16 and 21. The young women had been diagnosed with anogenital warts
      and self-managed their treatment with 0.5% podophyllotoxin solution. RESULTS:
      Self-management using 0.5% podophyllotoxin solution poses numerous difficulties.
      The nature of the treatment as a topical liquid is particularly testing for young
      women in terms of both application and genital pain, with implications for
      continuation of the treatment regime. The self-treatment challenges both personal
      integrity as well as interpersonal relations and creates a personal
      responsibility which appears to be somewhat overwhelming at times. CONCLUSIONS:
      Health care professionals need to recognize the challenge that self-treatment
      poses to their clients. The issues that create difficulty in relation to topical
      liquid treatment regimes and importantly can lead to poor adherence to the
      treatment regime and discontinuation could easily be overcome by the use of
      different preparations. Continuity of care provider across treatments and
      alternative mechanisms of support would not only address some of the aspects that
      young women raise as particularly embarrassing and shameful, but also improve
      quality of care and increase general satisfaction with service provision.

PMID- 22980738
TI  - Unexpected enlightening of a "female world". Male medical students' experiences
      of learning and performing the first pelvic examination.
AB  - OBJECTIVE: To gain a deeper understanding of how undergraduate male medical
      students experience a pelvic examination learning concept and performing the
      first pelvic examination (PE) on a professional patient. STUDY DESIGN: A
      qualitative study. In-depth interviews with 12 male medical students' after their
      involvement in a learning session about the PE, with professional patients and a
      supervising gynecologist as instructors. The interviews were analyzed according
      to the constant comparative method, a variety of content analysis, to acquire a
      deeper understanding of the students' experiences and the ongoing social
      processes. RESULTS: The essence of the entire analysis was "Unexpected
      enlightening of a 'female world'" and was identified from the three categories;
      "Not just any exam", "Professional supportive interaction" and "Humble
      awareness". The male students' most prominent concern was how to establish a
      professional rapport with the patient in the PE situation. Beneficial active
      support from the professional patient and the gynecologist assisted the students
      to overcome inherent barriers and facilitated the examination procedure. The
      informants gained "inside information" from the patients' perspective of being
      examined leading to a new awareness about an earlier unknown "female world" that
      is what women might go through before and during a PE and an humble understanding
      of how vulnerable it is to be placed in the examination position. CONCLUSION: The
      beneficial PE learning concept promoted an unexpected insight in what a woman
      might experience during a PE, creating a humble awareness of this vulnerable
      intimate situation and ideas for how to establish professional rapport.

PMID- 22980739
TI  - Chemical oxidation of a redox-active, ferrocene-containing cationic lipid:
      influence on interactions with DNA and characterization in the context of cell
      transfection.
AB  - We report an approach to the chemical oxidation of a ferrocene-containing
      cationic lipid [bis(11-ferrocenylundecyl)dimethylammonium bromide, BFDMA] that
      provides redox-based control over the delivery of DNA to cells. We demonstrate
      that BFDMA can be oxidized rapidly and quantitatively by treatment with
      Fe(III)sulfate. This chemical approach, while offering practical advantages
      compared to electrochemical methods used in past studies, was found to yield
      BFDMA/DNA lipoplexes that behave differently in the context of cell transfection
      from lipoplexes formed using electrochemically oxidized BFDMA. Specifically,
      while lipoplexes of the latter do not transfect cells efficiently, lipoplexes of
      chemically oxidized BFDMA promoted high levels of transgene expression (similar
      to levels promoted by reduced BFDMA). Characterization by SANS and cryo-TEM
      revealed lipoplexes of chemically and electrochemically oxidized BFDMA to both
      have amorphous nanostructures, but these lipoplexes differed significantly in
      size and zeta potential. Our results suggest that differences in zeta potential
      arise from the presence of residual Fe(2+) and Fe(3+) ions in samples of
      chemically oxidized BFDMA. Addition of the iron chelating agent EDTA to solutions
      of chemically oxidized BFDMA produced samples functionally similar to
      electrochemically oxidized BFDMA. These EDTA-treated samples could also be
      chemically reduced by treatment with ascorbic acid to produce samples of reduced
      BFDMA that do promote transfection. Our results demonstrate that entirely
      chemical approaches to oxidation and reduction can be used to achieve redox-based
      'on/off' control of cell transfection similar to that achieved using
      electrochemical methods.

PMID- 22980740
TI  - Characterization of polyplexes involving small RNA.
AB  - The purpose of the present study is to provide a tool for an efficient design and
      synthesis of non-viral vectors for small RNA delivery. The effects of properties
      of the polycation, such as molecular weight, charge density and backbone
      structure, to polyplex structure and physicochemical behavior were systematically
      evaluated. The condensing agents, polyethylenimine (PEI), chitosan (CS) and
      poly(allylamine) (PAA) were added to sRNA molecules at different N/P ratio. The
      efficiency of encapsulation and protection of sRNA, as well as polyplex size,
      zeta potential and morphology were followed and compared. The results show that
      PEI/sRNA polyplexes display a small size and positive zeta potential. However,
      for low molecular weights, this polycation is unable to protect sRNA in the
      presence of a decompacting agent. With chitosan, sRNA is efficiently compacted at
      high N/P ratios. The CS/sRNA complexes display small sizes, ca. 200 nm, positive
      surface charge and also good stability. Finally, the PAA/sRNA polyplexes were
      found to be the smallest at low N/P ratios, displaying a good encapsulation
      efficiency and high stability. A rationale for the experimental observations is
      provided using Monte Carlo simulation for systems with polycations of different
      length and charge density. The simulations showed that there is an interplay
      between the size of polycation chains and its charge density that define the
      degree of condensation for sRNA.

PMID- 22980741
TI  - Relationship of intraocular pressure and frequency of spontaneous retinal venous
      pulsation in primary open-angle glaucoma.
AB  - PURPOSE: To investigate the relationship of intraocular pressure (IOP) and the
      frequency of spontaneous venous pulsation (SVP) in primary open-angle glaucoma
      (POAG). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 229 eyes of 229
      patients with POAG and 205 eyes of 205 glaucoma suspects as a control. METHODS:
      The SVP was assessed using a confocal scanning laser ophthalmoscope (Spectralis
      HRA, Heidelberg Engineering, Heidelberg, Germany) movie tool. Patients with POAG
      were divided into 3 groups on the basis of the frequency distribution of
      untreated IOP: lower tertile (IOP <= 15 mmHg; group A), middle tertile (IOP >15
      and <= 21 mmHg; group B), and upper tertile (IOP >21 mmHg; group C). The
      frequency of SVP was compared between the glaucoma suspects and patients with
      POAG and among the 3 groups of POAG. Logistic regression analysis was performed
      to determine the factors associated with the frequency of SVP. MAIN OUTCOME
      MEASURES: Frequency of SVP in patients with POAG and glaucoma suspects. RESULTS:
      Spontaneous venous pulsation was more frequently found in glaucoma suspects than
      in patients with POAG (86.3% vs. 53.3%, P<0.0001). Within the POAG group, the
      frequency of SVP was significantly lower in group A (40.2%) than in group B
      (57.3%, P = 0.03) and group C (63.9%, P = 0.003). There was no significant
      difference between groups B and C (P = 0.42). In addition to IOP (P = 0.007),
      visual field mean deviation (MD) and refractive error were associated with the
      frequency of SVP (P<0.0001 and P = 0.011, respectively). When analyzed within the
      same stage of disease, SVP was less frequently found in group A than in group C
      in early (P = 0.011) and advanced (P = 0.044) glaucoma and marginally less
      frequently found in moderate glaucoma (P = 0.080). CONCLUSIONS: Spontaneous
      venous pulsation was less common in patients with POAG than in glaucoma suspects.
      Among the patients with POAG, SVP was less common in patients with low IOP at all
      stages of disease. These results are consistent with vascular factors having a
      more significant role in patients with POAG with low IOP than in patients with
      POAG with higher IOP.

PMID- 22980742
TI  - Iris melanoma management with iodine-125 plaque radiotherapy in 144 patients:
      impact of melanoma-related glaucoma on outcomes.
AB  - PURPOSE: To evaluate the outcomes of iris melanoma managed with plaque
      radiotherapy on the basis of the initial presence or absence of glaucoma. DESIGN:
      Retrospective, comparative case series. PARTICIPANTS: A total of 144 patients.
      INTERVENTION: Custom-designed iodine-125 plaque radiotherapy delivering planned
      8000 cGy to melanoma apex using transcorneal application. MAIN OUTCOME MEASURES:
      Tumor control and treatment-related complications. RESULTS: Of 144 patients with
      iris melanoma, glaucoma was present at the initial visit in 58 (40%). Causes of
      elevated intraocular pressure included angle infiltration by melanoma in 50
      patients (86%), angle neovascularization in 4 patients (7%), and hyphema in 4
      patients (7%). At presentation, the eyes displaying iris melanoma with glaucoma
      (vs. without glaucoma) were statistically more likely to display angle tumor (66%
      vs. 43%), with minimal thickness (1.9 vs. 2.9 mm), and melanoma seeding in iris
      stroma (7 vs. 3 clock hours) and angle (5 vs. 2 clock hours). Plaque radiotherapy
      was performed in all cases. Kaplan-Meier estimates at 7 years post-treatment
      revealed no statistical differences in outcomes of local recurrence (14% vs.
      15%), enucleation (14% vs. 11%), or metastasis (2% vs. 0%) comparing eyes with
      and without glaucoma. Of the entire group, multivariate analysis for factors
      predictive of recurrence included partial (vs. complete) anterior segment
      irradiation and postradiotherapy glaucoma. Factors related to enucleation
      included diabetes mellitus, poor initial visual acuity, higher radiation dose to
      tumor apex, and tumor recurrence. There were no factors predictive of metastasis.
      CONCLUSIONS: Iodine-125 plaque radiotherapy provides adequate tumor control for
      iris melanoma with a low metastatic potential of 1% at 7 years. Iris melanoma
      with secondary glaucoma showed a statistically significant greater likelihood of
      flat tumor with iris and angle seeding and no difference in outcomes compared
      with eyes without glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 22980743
TI  - Morphologic and functional changes in retinal vessels associated with branch
      retinal vein occlusion.
AB  - OBJECTIVE: To study the morphologic and functional changes in retinal veins of
      eyes affected with branch retinal vein occlusion (BRVO) by thin sectioning with
      optical coherence tomography (OCT). DESIGN: Prospective, observational, cross
      sectional study. PARTICIPANTS: Twenty-five consecutive patients (25 eyes) with
      acute BRVO. METHODS: Major retinal veins, arteries, and arteriovenous (A/V)
      crossing were examined by sequential thin sectioning by Spectralis HRA+OCT
      (Heidelberg Engineering, Heidelberg, Germany). The retinal blood flow was
      mimicked in vitro and scanned with Spectralis HRA+OCT. MAIN OUTCOME MEASURES:
      Morphologic characteristics of normal and BRVO-affected retinal vessels seen in
      OCT sections. RESULTS: Cross-sectional OCT images revealed physiologic retinal
      vessels as oval configurations with 4 distinctive hyperreflectivities in a line.
      The vessel walls showed the innermost and outermost hyperreflectivity, and the
      blood flow showed internal paired hyperreflectivities with an hourglass shape. No
      eye with disturbed blood flow due to BRVO showed this internal hyperreflectivity
      pattern. In vitro, OCT sections of the blood within the glass tube without flow
      showed homogeneous reflectivities. Increased blood flow velocity resulted in the
      development of heterogeneous internal reflectivity and hourglass-shaped
      hyperreflectivities. In all eyes with acute BRVO, sequential sectioning with OCT
      visualized 3-dimensional vascular architecture and the intravascular conditions
      at the A/V crossing. At the affected A/V crossing, arterial overcrossing was seen
      in 17 eyes and venous overcrossing was seen in 8 eyes. In eyes with arterial
      overcrossing, the retinal vein seemed to run deep under the artery at the A/V
      crossing, and the venous lumen often appeared to be preserved even at the A/V
      crossing. In all eyes with venous overcrossing, the retinal vein appeared to be
      compressed and choked between the internal limiting membrane and the arterial
      wall at the A/V crossing. Optical coherence tomography sectioning showed
      intravenous thrombi in 21 eyes, and the thrombi were detected downstream of the
      A/V crossing in all the cases. The detection of thrombus was significantly
      associated with ischemic pattern in BRVO (P=0.036). CONCLUSIONS: In eyes with
      BRVO, sequential thin sections with OCT visualized 3-dimensional retinal
      vasculature. The present OCT findings suggest that BRVO may occur by 2 different
      mechanisms, depending on the relative anatomic positions of the crossing vessels.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 22980744
TI  - Spinal SGK1/GRASP-1/Rab4 is involved in complete Freund's adjuvant-induced
      inflammatory pain via regulating dorsal horn GluR1-containing AMPA receptor
      trafficking in rats.
AB  - The elusiveness of the mechanism underlying pain is a major impediment in
      developing effective clinical treatments. We examined whether the phosphorylation
      of spinal serum- and glucocorticoid-inducible kinase 1 (SGK1) and downstream
      glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1)/Rab4
      dependent GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor (AMPAR) recycling play a role in inflammatory pain. After
      intraplantar injection of complete Freund's adjuvant (CFA), we assessed thermal
      hyperalgesia using the Hargreaves test and analyzed dorsal horn samples (L4-5)
      using Western blotting, coprecipitation, and immunofluorescence. CFA
      administration provoked behavioral hyperalgesia along with SGK1 phosphorylation,
      GluR1 trafficking from the cytosol to the membrane, and phosphorylated SGK1
      (pSGK1)-GRASP-1, GRASP-1-Rab4, and Rab4-GluR1 coprecipitation in the ipsilateral
      dorsal horn. In the dorsal horns of hyperalgesic rats, CFA-enhanced pSGK1 was
      demonstrated to be colocalized with NeuN, GRASP-1, Rab4, and GluR1 by
      immunofluorescence. GSK-650394 (an SGK1 activation antagonist, 1, 10, and 30 MUM,
      10 MUL/rat, intrathecally) dose-dependently prevented CFA-induced pain behavior
      and the associated SGK1 phosphorylation, GluR1 trafficking, and protein-protein
      interactions at 1 day after CFA administration. Intrathecal 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX, an AMPAR antagonist, 1, 3, and 10 MUM, 10
      MUL/rat) attenuated the hyperalgesia and GluR1 trafficking caused by CFA;
      however, it had no effect on SGK1 phosphorylation. Small interfering RNA
      targeting Rab4 hindered the CFA-induced hyperalgesia and the associated GluR1
      trafficking and Rab4-GluR1 coprecipitation. Our results suggest that spinal SGK1
      phosphorylation, which subsequently triggers the GRASP-1/Rab4 cascade, plays a
      pivotal role in CFA-induced inflammatory pain by regulating GluR1-containing
      AMPAR recycling in the dorsal horn.

PMID- 22980745
TI  - A case of pain, motor impairment, and swelling of the arm after acute herpes
      zoster infection.
AB  - Complex regional pain syndrome (CRPS) and postherpetic neuralgia (PHN) represent
      neuropathic pain syndromes that may appear with similar clinical signs and
      symptoms. Medical history and clinical distribution of symptoms and signs (PHN
      typically at the thorax; CRPS typically at the limbs) is obvious in most cases,
      helping to discriminate between both disorders. Here, we present a patient
      suffering from CRPS II following PHN of one upper extremity. This case
      demonstrates that both etiology and part of the body affected by a neuropathy
      influence the pain phenotype.

PMID- 22980746
TI  - Quantitative sensory testing somatosensory profiles in patients with cervical
      radiculopathy are distinct from those in patients with nonspecific neck-arm pain.
AB  - The aim of this study was to establish the somatosensory profiles of patients
      with cervical radiculopathy and patients with nonspecific neck-arm pain
      associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles
      were compared to healthy control (HC) subjects and a positive control group
      comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of
      thermal and mechanical detection and pain thresholds, pain sensitivity and
      responsiveness to repetitive noxious mechanical stimulation was performed in the
      maximal pain area, the corresponding dermatome and foot of 23 patients with
      painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7
      dermatomal pain distribution, 31 HC and 22 patients with FM. For both neck-arm
      pain groups, all QST parameters were within the 95% confidence interval of HC
      data. Patients with cervical radiculopathy were characterised by localised loss
      of function (thermal, mechanical, vibration detection P<.009) in the maximal pain
      area and dermatome (thermal detection, vibration detection, pressure pain
      sensitivity P<.04), consistent with peripheral neuronal damage. Both neck-arm
      pain groups demonstrated increased cold sensitivity in their maximal pain area
      (P<.03) and the foot (P<.009), and this was also the dominant sensory
      characteristic in patients with NSNAP. Both neck-arm pain groups differed from
      patients with FM, the latter characterised by a widespread gain of function in
      most nociceptive parameters (thermal, pressure, mechanical pain sensitivity
      P<.027). Despite commonalities in pain characteristics between the 2 neck-arm
      pain groups, distinct sensory profiles were demonstrated for each group.

PMID- 22980747
TI  - Dysfunctional telomeres in primary cells from Fanconi anemia FANCD2 patients.
AB  - BACKGROUND: Fanconi anemia (FA) is characterized by sensitivity to DNA cross
      linking agents, mild cellular, and marked clinical radio sensitivity. In this
      study we investigated telomeric abnormalities of non-immortalized primary cells
      (lymphocytes and fibroblasts) derived from FA patients of the FA-D2
      complementation group, which provides a more accurate physiological assessment
      than is possible with transformed cells or animal models. RESULTS: We analyzed
      telomere length, telomere dysfunction-induced foci (TIFs), sister chromatid
      exchanges (SCE), telomere sister chromatid exchanges (T-SCE), apoptosis and
      expression of shelterin components TRF1 and TRF2. FANCD2 lymphocytes exhibited
      multiple types of telomeric abnormalities, including premature telomere
      shortening, increase in telomeric recombination and aberrant telomeric structures
      ranging from fragile to long-string extended telomeres. The baseline incidence of
      SCE in FANCD2 lymphocytes was reduced when compared to control, but in response
      to diepoxybutane (DEB) the 2-fold higher rate of SCE was observed. In contrast,
      control lymphocytes showed decreased SCE incidence in response to DEB treatment.
      FANCD2 fibroblasts revealed a high percentage of TIFs, decreased expression of
      TRF1 and invariable expression of TRF2. The percentage of TIFs inversely
      correlated with telomere length, emphasizing that telomere shortening is the
      major reason for the loss of telomere capping function. Upon irradiation, a
      significant decrease of TIFs was observed at all recovery times. Surprisingly, a
      considerable percentage of TIF positive cells disappeared at the same time when
      incidence of gamma-H2AX foci was maximal. Both FANCD2 leucocytes and fibroblasts
      appeared to die spontaneously at higher rate than control. This trend was more
      evident upon irradiation; the percentage of leucocytes underwent apoptosis was
      2.59- fold higher than that in control, while fibroblasts exhibited a 2- h delay
      before entering apoptosis. CONCLUSION: The results of our study showed that
      primary cells originating from FA-D2 patients display shorten telomeres, elevated
      incidence of T-SCEs and high frequency of TIFs. Disappearance of TIFs in early
      response to irradiation represent distinctive feature of FANCD2 cells that should
      be examined further.

PMID- 22980748
TI  - [Impact of family support on depressive complaints in the elderly in Santiago,
      Chile].
AB  - INTRODUCTION: Epidemiological changes can have an effect on social and, and in
      particular, family ties, which are important elements in the mental health of
      older people. The objective of this study was to evaluate the impact of family
      support on depressive disorders in older people of the community. MATERIAL AND
      METHODS: Face to face interviews were conducted on a representative sample of
      adults 60 years and older, living in urban area of Santiago de Chile. The
      information on depressive disorders was related to family composition, emotional
      and instrumental support, presence of conflict, health self-perception,
      functionality and self-efficiency. Data were analyzed using logistic regression
      models. RESULTS: From a total of 394 participants, 62% females, mean age 74 years
      (SD=8.1), 16% felt depressed almost every day. Depressive disorders were
      significantly associated in regression models with impaired self-perception of
      health and efficacy, lower instrumental support, and with the presence of
      conflict. The variable that most contributed to the model was self-rated poor
      health, increasing the odds of depressive disorders by 3.2. CONCLUSIONS: Poor
      perception of health was the main determining factor for depressive complaints in
      older people, followed by lower family support, specifically instrumental
      support, and the presence of conflict. This information can help future programs
      in order to improve the quality of life in older people.

PMID- 22980749
TI  - [Communication, mass media and quaternary prevention].

PMID- 22980752
TI  - Computer-aided techniques for chromogenic immunohistochemistry: status and
      directions.
AB  - Although immunohistochemistry (IHC) is a popular imaging technique, the
      quantitative analysis of IHC images via computer-aided methods is an emerging
      field that is gaining more and more importance thanks to the new developments in
      digital high-throughput scanners. In this paper, we discuss the main steps of IHC
      and review the techniques for computer-aided chromogenic IHC analysis, including
      methods to determine the location of interest of the antigens and quantify their
      activations. Moreover, we discuss the issues arising from the standardization of
      the immunostaining process, that are generally overlooked by the current
      literature, and finally provide requirements for reliable computer-aided IHC
      quantification.

PMID- 22980753
TI  - Acute mastoiditis--the role of radiology.
AB  - Acute mastoiditis is a commonly occurring condition in children and adults, and
      one that most radiologists will come across at some point during their on-call
      duties. Acute mastoiditis is usually clinically apparent. However, the
      complications, especially the intracranial ones, can be more insidious and may
      have fatal consequences. Therefore, it is imperative that the radiologist is well
      versed in identifying these. Local spread of infection from the mastoids and
      middle ear cleft may occur via four routes: bone erosion, thrombophlebitis,
      periphlebitis, and via the anatomical pathways. The role of radiology is largely
      to demonstrate the complications of mastoiditis, which can be clinically occult
      and are often serious; this article will highlight these complications.

PMID- 22980754
TI  - [Laboratory safety: key in patient safety].

PMID- 22980755
TI  - [Knowledge and attitudes as regards Living Wills between Primary and Specialised
      Care Doctors in the Ferrol Health Area].
AB  - OBJECTIVES: To evaluate the knowledge, the experience and the attitudes of the
      health professionals of Primary (PC) and Specialized (SC) Carein our Health Area
      with respect to Living Wills (LW). MATERIAL AND METHOD: Descriptive, cross
      sectional study, by means of a survey addressed to PC and SC doctors Ferrol
      (Galicia, Spain) Health Area RESULTS: A total of 120 (42.85%) doctors completed
      the questionnaire.The professionals self-assessed their level of knowledge with a
      mean of 3.83 (rank from 0 to 10). Only 21 professionals (17.5%) had objective
      knowledge of LW, that is to say, they fulfilled the following premises: they had
      read some pieces of LW legislation, had read an LW document and knew the elements
      that could figure in it. There were differences that verged on the statistical
      significance in the objective knowledge between PC and SC doctors (11.7% versus
      23.3%, P= .093) and between professionals with under 10 years of professional
      experience and those with more than 10 years (6.9% versus 21.1%, P=.081). These
      differences reached statistical significance in some of the items that valued the
      objective knowledge. A few professionals (28 (23.3%)), had explained to their
      patients the convenience of having written an LW document, and even fewer (8
      (6,7%)) had helped patients with writing one. CONCLUSIONS: The knowledge of
      health care professionals can be clearly improved. The highest deficiency was
      found between PC professionals and those with less experience. Nevertheless, they
      showed a favourable attitude towards them.

PMID- 22980756
TI  - [Lean logistics management in healthcare: a case study].
AB  - OBJECTIVE: To study the applicability of the principles of Lean Production to
      manage the supply chain of a hospital. In particular, to determine which Lean
      practices and principles are applicable, the benefits obtained and the main
      barriers for its implementation. Managing the hospital supply chain is an
      important issue, both for its effect on the quality of care and its impact on
      costs. METHODS: This study is based on a case study. STUDY PERIOD: 2005-10.
      SCOPE: Hospital Virgen Macarena in Seville. Process of implementing a
      comprehensive logistics management plan based on Lean principles and
      technological investments. RESULTS: The implementation of the comprehensive plan
      has reduced inventory, decreased lead times and improved service quality. Also,
      there have been other important improvements: enhanced employee satisfaction and
      increased staff productivity, both dedicated to health and the logistics.
      CONCLUSIONS: The experience analysed has shown the applicability and
      appropriateness of Lean principles and some of its techniques in managing the
      logistics of hospitals. It also identifies some of the main difficulties that may
      arise.

PMID- 22980757
TI  - Chronic treatment of female tammar wallabies with deslorelin implants during
      pouch life: effects on reproductive maturation.
AB  - The present study reports on attempts to delay puberty in a model marsupial
      species using the gonadotrophin-releasing hormone (GnRH) agonist deslorelin.
      Female tammar wallaby pouch young received deslorelin (5 mg) or placebo implants
      (n=8/group) when they were 193+/-2 days old. Sexual maturity was significantly
      delayed in deslorelin-treated animals, with the first successful production of
      offspring in treated and control animals occurring at 813+/-62 and 430+/-42 days
      of age, respectively. This delay was associated with a period of retarded pouch
      and teat development. Progesterone concentrations remained at basal levels
      throughout the first breeding season, indicating the absence of luteal cycles in
      treated females. Recovery and maturation of the hypothalamic-pituitary axis was a
      gradual process. Treated animals failed to respond to GnRH challenge at 12 months
      of age and had a reduced LH response at 18 months of age, before attaining full
      responsiveness by 24 months of age. Despite this apparent pituitary recovery by
      24 months of age, as evidenced by complete teat eversion and LH responsiveness to
      GnRH, the time to first parturition was significantly delayed beyond this time in
      three females. This suggests that there may be longer-lasting effects at the
      level of the ovary and/or on FSH secretion. The significant delay in the onset of
      sexual maturation in response to chronic GnRH agonist treatment in this model
      marsupial species may be of practical significance to the management of fertility
      in captive and semi-free range marsupial populations.

PMID- 22980758
TI  - Host actin remodeling and protection from malaria by hemoglobinopathies.
AB  - Many intracellular pathogens remodel the actin of their host cells, and the human
      malaria parasite Plasmodium falciparum is no exception to this rule. The
      surprising finding is that several hemoglobinopathies that protect carriers from
      severe malaria may do so by interfering with host actin reorganization. Here we
      discuss our current understanding of actin remodeling in P. falciparum-infected
      erythrocytes, how hemoglobinopathies interfere with this process, and how
      impaired host actin remodeling affects the virulence of P. falciparum.

PMID- 22980759
TI  - The design and interpretation of laboratory assays measuring mosquito
      transmission of Plasmodium.
AB  - Since 2010 two global reviews of malaria research have recognized that local
      elimination and eradication of Plasmodium parasites are key drivers for further
      experimentation. To achieve these ambitious objectives it is universally
      recognized we must reduce malaria transmission through the mosquito vectors. A
      plethora of new laboratory assays are being developed to interrogate malaria
      transmission from the gametocyte to the sporozoite stage: assays that augment
      well-established field protocols to determine the entomological inoculation rate.
      However, the diverse readouts of these assays are not directly comparable. Here
      we attempt to identify the utility of each assay and provide rational frameworks
      by which to compare the impacts recorded by the diverse methodologies.

PMID- 22980760
TI  - Muscle MRI in Becker muscular dystrophy.
AB  - The aim of this study was to evaluate pelvis and lower limb muscle MRI scans of
      46 patients affected by Becker muscular dystrophy (BMD), subdivided according to
      disease severity, ranging from clinically asymptomatic patients to patients who
      had lost ambulation. We found a distinct pattern on muscle imaging characterized
      by prominent involvement of the gluteus maximus and medius, adductor magnus,
      biceps femoris long head, semimembranosus and vasti. This pattern was consistent
      in all the 25 symptomatic patients. Milder changes in the same muscles were found
      in 13 of the 21 asymptomatic cases. The other 8 asymptomatic patients had a
      normal scan. The severity of muscle involvement was significantly correlated with
      age. Our results suggest that a distinct pattern of muscle involvement can be
      detected in BMD. The early identification of muscle changes in a proportion of
      asymptomatic patients may be useful as an additional tool in the diagnostic
      workup.

PMID- 22980761
TI  - Exercise might bias skeletal-muscle fat fraction calculation from Dixon images.
AB  - We examined the influence of a single exercise session on quantitative muscle fat
      fraction MRI measurements. Ten healthy volunteers were scanned on a 3T body
      scanner before and after a session of bilateral squats until muscular fatigue.
      Axial in- and opposed phase images were acquired at a fixed distance from the
      knee joint and fat fractions were calculated using a 2-point Dixon technique as
      well as muscle cross sectional area at the same position. After the squat
      session, calculated fat fraction in the quadriceps bilaterally appeared to be
      significantly decreased, while all but one non-exercised muscles showed no
      change. In conclusion exercise might modify the measured apparent fat fraction.
      Trials using quantitative MRI should consider the timing of scanning sessions and
      physical examinations to avoid bias caused by the influence of exercise on
      measurements.

PMID- 22980762
TI  - MRI/MRS evaluation of a female carrier of Duchenne muscular dystrophy.
AB  - The purpose of this study was to evaluate skeletal muscle composition of lower
      extremity muscles in a manifesting female carrier of Duchenne muscular dystrophy
      (MFC(DMD)) using magnetic resonance imaging (MRI) and spectroscopy (MRS). MRI/MRS
      was performed on the lower extremities and heart of a MFC(DMD) (47 years, 51 kg)
      on four occasions within 21 months and in a control subject. Heterogeneity and
      asymmetry among muscles in the MFC(DMD) was observed in lipid fraction and mean
      transverse relaxation time (T(2)) of lower extremity muscles with some muscles
      presenting as unaffected (e.g., rectus femoris) and others showing substantial
      deterioration and lipid infiltration (e.g., vasti muscles). There was an
      association of abnormal MRI findings and strength and motor function. Over the 21
      months a small decrease in CSA(max) and increase in lipid fraction and T(2) was
      observed in the MFC(DMD) in some muscles. In summary, this MFC(DMD) revealed
      significant imaging evidence of pathologic heterogeneity among muscles.
      Furthermore, this study shows the feasibility of combining various quantitative
      MRI and MRS approaches to monitor skeletal muscle involvement.

PMID- 22980763
TI  - Muscle MRI findings in limb girdle muscular dystrophy type 2L.
AB  - Limb girdle muscular dystrophy type 2L (LGMD2L) is an adult-onset slowly
      progressive muscular dystrophy associated with recessive mutations in the ANO5
      gene. We analysed the muscle MRI pattern in a cohort of 25 LGMD2L patients in
      order to understand the extent and progression of muscle pathology in LGM2L and
      assess if muscle MRI might help in the diagnostic work-up of these patients. Our
      results showed a homogeneous pattern of muscle pathology on muscle MRI, with a
      predominant involvement of the posterior compartment muscles in both the thighs
      and calves. The muscles of the anterior compartments in the leg together with the
      sartorius and gracilis muscles were best preserved, which partially overlaps with
      patterns observed for other recessive LGMDs. Muscle MRI therefore does not appear
      to be as useful in the diagnostic work up of LGMD2L as for other neuromuscular
      diseases, such as Bethlem myopathy or myofibrillar myopathy.

PMID- 22980764
TI  - Selective pattern of muscle involvement seen in distal muscular dystrophy
      associated with anoctamin 5 mutations: a follow-up muscle MRI study.
AB  - Anoctaminopathy is a new muscular dystrophy caused by mutations in the ANO5 gene.
      ANO5 mutations cause distal and proximal phenotypes. We report here a follow-up
      muscle MRI study on five patients affected by distal form of anoctaminopathy. T1
      weighted scans showed subsequent involvement of gastrocnemius medialis and
      soleus, hip adductors, hamstrings, gastrocnemius lateralis and quadriceps
      muscles, and later on tensor fascia lata, gluteus minimus and biceps brachii
      muscles, respectively. The STIR weighted images showed in the early stages widely
      distributed hyperintense signals, myoedema, in the adductors, hamstrings, and
      quadriceps muscles, which at that time have normal T1 signals. All patients
      showed asymmetry of muscle involvement both clinically and on muscle imaging. The
      progression of muscle involvement was relatively slow. We conclude that the
      pattern of muscle involvement seen in patients with distal myopathy with
      anoctamin 5 mutations (MMD3) is typical and can thus be useful during the
      differential diagnosis process allowing for a more targeted molecular approach.

PMID- 22980765
TI  - Whole-Body muscle MRI in a series of patients with congenital myopathy related to
      TPM2 gene mutations.
AB  - Beta-tropomyosin 2 (TPM2) gene mutations are a rare cause of congenital myopathy
      with variable clinical and histological features. We describe muscle involvement
      using Whole-Body muscle Magnetic Resonance Imaging (WBMRI) in 8 individuals with
      genetically proven TPM2 mutations and different clinical and histological
      features (nemaline myopathy, 'cap disease', Bethlem-like phenotype,
      arthrogryposis). Most patients shared a recognizable MRI pattern with the
      involvement of masticatory and distal lower leg muscles. The lower leg showed
      constant soleus muscle involvement, and often also involvement of peroneus,
      tibialis anterior, and toe flexor muscles. Pelvic and shoulder girdles, and upper
      limbs muscles were quite spared. Two adult subjects (a patient and a
      paucisymptomatic parent) had a more diffuse involvement with striking fat
      infiltration of the rectus femoris muscle. Two children showed variant findings:
      one presented with masseter involvement associated with severe axial fat
      infiltration, the second had masticatory and distal leg muscle involvement
      (soleus and gastrocnemius muscles). Our study suggests that, independently of the
      clinical and histological presentation, most patients with TPM2 mutations show a
      predominant involvement of masticatory and distal leg muscles with the other
      regions relatively spared. More spread involvement may be observed. This cephalic
      distal MRI pattern is not frequent in other known myopathies.

PMID- 22980766
TI  - Trunk muscle involvement in late-onset Pompe disease: study of thirty patients.
AB  - Late-onset Pompe disease is characterized by progressive weakness involving
      proximal limb and respiratory muscles. Recently, treatment with enzyme
      replacement therapy (ERT) has been introduced partially improving patients'
      prognosis, but a standard consensus on when to start ERT is still lacking. There
      is also a lack of biomarkers related to the clinical progression of the disease.
      Here we used muscle magnetic resonance imaging (MRI) or computed tomography (CT)
      to study the abdominal and paravertebral muscles of 30 late-onset Pompe patients
      at different stages of disease. We observed a selective pattern of muscle damage,
      with early involvement of the Multifidus muscle, followed by the Obliquus
      internus abdominis and Longissimus muscle. Some degree of trunk involvement on
      MRI occurred even in asymptomatic patients. Severity of muscle involvement in MRI
      correlated with patients' functional stage. We suggest that: (a) the combination
      of paravertebral and abdominal muscle involvement may serve as a useful tool in
      the diagnostic work-up of patients with a clinical suspicion of Pompe disease;
      (b) trunk abnormalities appear at very early stages of disease and even in
      asymptomatic patients, possibly "announcing" the onset of the disease and thus
      the need for a closer clinical follow-up.

PMID- 22980767
TI  - Applications of MRI in muscle diseases.

PMID- 22980768
TI  - TREAT-NMD workshop: pattern recognition in genetic muscle diseases using muscle
      MRI: 25-26 February 2011, Rome, Italy.

PMID- 22980769
TI  - Towards harmonization of protocols for MRI outcome measures in skeletal muscle
      studies: consensus recommendations from two TREAT-NMD NMR workshops, 2 May 2010,
      Stockholm, Sweden, 1-2 October 2009, Paris, France.

PMID- 22980770
TI  - Whole body muscle MRI protocol: pattern recognition in early onset NM disorders.
AB  - A paediatric and adult whole-body MRI (WB-MRI) protocol using a 1.5-T MRI system
      was used to examine 117 individuals (106 patients, 11 asymptomatic relatives).
      Genetic diagnosis was obtained in 38 subjects (RYR1, LMNA, COL6, DNM2, GAA, TPM2,
      SGCA, MYH7, NEB, SMN, FKBP14). T1-TSE WB-MRI sequences were abnormal in 67% of
      patients and 27% of asymptomatic relatives. Multiple striped signal abnormalities
      ('tiger-like') were very specific for COLVI-related myopathy. Distinct
      involvement of muscles in the head, neck, trunk, girdles and limbs was observed
      in patients with RYR1, SEPN1, GAA, LMNA or TPM2 mutations. Abnormalities and
      pattern recognition were more frequent in patients studied due to rigid spine
      syndrome (80% abnormal, recognisable in 75% of cases), hyperlaxity syndrome (75%;
      50%) or with confirmed myopathy but absence of these markers (71%; 40%). Pattern
      was consistent with the molecular diagnosis in 97%. Mild clinical involvement was
      revealed by muscle testing in three parents with abnormal WB-MRI. The Garches WB
      MRI protocol is suitable for a large spectrum of adults and children with early
      onset neuromuscular disorders and can be used as an effective screening test in
      relatives. Recognition of characteristic patterns of abnormalities is improved by
      whole-body scanning compared with sequential MRI and, therefore, diagnostic
      impact is greater.

PMID- 22980771
TI  - Comprehensive longitudinal characterization of canine muscular dystrophy by
      serial NMR imaging of GRMD dogs.
AB  - The Golden Retriever Muscular Dystrophy (GRMD) dog is the closest animal
      counterpart of Duchenne muscular dystrophy in humans and has, for this reason,
      increasingly been used in preclinical therapeutic trials for this disease. The
      aim of this study was to describe the abnormalities in canine dystrophic muscle
      non-invasively, quantitatively, thoroughly and serially by means of NMR imaging.
      Thoracic and pelvic limbs of five healthy and five GRMD dogs were imaged in a 3T
      NMR scanner at 2, 4, 6 and 9months of age. Standard and fat-saturated T(1)-, T(2)
      and proton-density-weighted images were acquired. A measurement of T(1) and a
      two-hour kinetic study of muscle enhancement after gadolinium-chelate injection
      were also performed. Ten out of the 15 indices evaluated differed between healthy
      and GRMD dogs. The maximal relative enhancement after gadolinium injection and
      the proton-density-weighted/T(2)-weighted signal ratio were the most
      discriminating indices. Inter-muscle heterogeneity was found to vary
      significantly for most of the indices. The body of data that has been acquired
      here will help in designing and interpreting preclinical trials using dystrophin
      deficient dogs.

PMID- 22980772
TI  - Severe pollution of PCDD/Fs and dioxin-like PCBs in sediments from Lake Shihwa,
      Korea: tracking the source.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and
      dioxin-like polychlorinated biphenyls (DL-PCBs) were determined in surface
      sediments from Lake Shihwa and from creeks that discharge into this artificial
      lake. The toxic equivalents (TEQs) in sediments ranged from 1.0 to 1770 pg/g dry
      weight, which were some of the highest values ever reported so far for coastal
      sediments on a global basis. The concentrations of PCDD/Fs and DL-PCBs decreased
      with increasing distance from the creeks to offshore regions of the lake. Based
      on a multivariate statistical analysis and congener profiles, it was found that
      high contamination by PCDD/Fs in creek sediments collected around Lake Shihwa was
      associated with releases from chlor-alkali processes. Significant correlations
      were found for total organic carbon content and the concentrations of highly
      chlorinated PCDD/F congeners. This is the first report to document chlor-alkali
      processes as a significant source of PCDD/F contamination in Korean coastal
      waters.

PMID- 22980773
TI  - The continuing decline of coral reefs in Bahrain.
AB  - Historically coral reefs of Bahrain were among the most extensive in the southern
      basin of the Arabian Gulf. However, Bahrain's reefs have undergone significant
      decline in the last four decades as a result of large-scale coastal development
      and elevated sea surface temperature events. Here we quantitatively surveyed six
      sites including most major coral reef habitats around Bahrain and a reef located
      72 km offshore. Fleshy and turf algae now dominate Bahrain's reefs (mean: 72%
      cover), and live coral cover is low (mean: 5.1%). Formerly dominant Acropora were
      not observed at any site. The offshore Bulthama reef had the highest coral cover
      (16.3%) and species richness (22 of the 23 species observed, 13 of which were
      exclusive to this site). All reefs for which recent and historical data are
      available show continued degradation, and it is unlikely that they will recover
      under continuing coastal development and projected climate change impacts.

PMID- 22980774
TI  - Sewage organic markers in surface sediments around the Brazilian Antarctic
      station: results from the 2009/10 austral summer and historical tendencies.
AB  - The discharge of sewage into the Antarctic marine environments by scientific
      stations has resulted in local changes in these pristine sites. To assess the
      distribution and concentration of sewage indicators from the Brazilian Antarctic
      station, sediments were sampled during the 2009/10 austral summer at four points
      (water depth of 20 and 60 m). Concentrations of faecal sterols and linear
      alkylbenzenes (LABs) ranged from <0.01 to 0.17 MUg g-1 and <1.0 to 46.5 ng g-1
      dry weight, respectively. Maximum concentration of faecal sterols was similar to
      the value previously calculated as the background level for this area (0.19 MUg g
      1), and it is lower than the concentration observed in previous studies (1997
      2008), whereas the LABs concentrations remained practically constant (35 ng g-1).
      Despite the low concentrations of sewage markers, the permanent human activities
      in the region require monitoring programs to determine continuing trends and
      prevent the increase of anthropogenic impacts.

PMID- 22980775
TI  - The 101 percent in Lund-Browder charts--a commentary.

PMID- 22980776
TI  - Mechanism of drug resistance, characterization of plasmid-borne determinants and
      transformation study in P. aeruginosa from burn and ICU units-its susceptibility
      pattern.
AB  - The transfer of drug resistance between hospital pathogens has led to alarming
      increase of multidrug resistant strains imposing therapeutic challenges. These
      resistant isolates harbor various mechanisms to counteract the drugs administered
      and have been reported to deliver these factors to sensitive strains in hostile
      environment. The present study aimed to screen for multidrug resistant
      Pseudomonas aeruginosa strains for the production of extended-spectrum beta
      lactamases, metallo-beta-lactamases, AmpC beta-lactamase, drug efflux phenotypes
      and co-transfer the resistance for cephalosporin and other non-beta lactam
      antibiotics in CaCl2 treated drug sensitive E. coli strains. From the 87 samples
      processed about 23 isolates of P. aeruginosa were ESBL and MBL positive, 5 (20%)
      were found to be AmpC beta-lactamase producers, efflux mechanism was observed in
      8 isolates, 15 isolates had MIC of 16 MUg/ml. A putative efflux mechanism was
      observed in 8 out of 23 isolates that showed decrease in the MIC of meropenem
      with reserpine. The plasmid profile was characterized for all the common isolates
      obtained from burn and ICU units. About 69.66% of E. coli recombinants scored
      positive for both beta lactam and non-beta lactam antibiotics is due to co
      transfer of resistant plasmid obtained from P. aeruginosa.

PMID- 22980777
TI  - Outbreak of yersiniosis in Egyptian rousette bats (Rousettus aegyptiacus) caused
      by Yersinia pseudotuberculosis serotype 4b.
AB  - This report describes an outbreak of yersiniosis in Egyptian rousette bats
      (Rousettus aegyptiacus) caused by Yersinia pseudotuberculosis serotype 4b. Twelve
      of 61 bats died between November and December 2008 or in May 2009. The bats often
      displayed multiple yellow-white nodules in the spleen and liver. Microscopically,
      these consisted of focal necrosis accompanied by inflammatory cell infiltration
      and colonies of gram-negative bacilli. The bacterial colonies were identified
      immunohistochemically as Y. pseudotuberculosis O4 and Y. pseudotuberculosis
      serotype 4b was identified by bacteriological examination. Polymerase chain
      reaction demonstrated that the isolate harboured the virulence genes virF, inv
      and ypmA. YPMa is as a superantigenic toxin that is associated with acute
      systemic infection in man and may contribute to the virulence of Y.
      pseudotuberculosis in bats.

PMID- 22980778
TI  - The ability to modulate peripersonal and extrapersonal reach space via tool use
      among the elderly.
AB  - Functional decrements associated with increasing aging may restrict daily
      activities and require use of tools (e.g., canes and walkers) for postural
      control and locomotion. Therefore, we examined older adults' ability to plan
      reach movements with their arm and tools of 20 and 40 cm in length. Twenty-seven
      participants between the ages of 55 and 92 years were divided into two groups,
      <75 and >76 years. The task required participants to estimate reach via use of
      motor imagery in regard to seven targets randomly presented in peripersonal and
      extrapersonal space. Each condition consisted of a block of 21 trials for the ARM
      and TOOL and a "switch-block" of 7 trials with the opposite condition. The
      procedure was repeated for both tool lengths and presented in counterbalanced
      order. Analysis of variance (ANOVA) results revealed a significant difference in
      the switch-blocks, suggesting that participants were more accurate when they
      switched from ARM to TOOL (extension) in comparison to TOOL to ARM (retraction).
      In addition, a correlation analysis indicated a negative relationship for
      accuracy in the 40 cm tool condition and age. In view of the total sample, two
      findings warrant further consideration. For both tool lengths, retraction from
      TOOL to ARM was more difficult than extension from ARM to TOOL. And specifically
      to the 40 cm tool, accuracy decreased as age increased. In addition to gaining
      information about aging of the neuro-cognitive processes associated with spatial
      representation, these outcomes may have implications for physical safety and
      rehabilitation with older persons.

PMID- 22980779
TI  - Protective effects of sweet orange (Citrus sinensis) peel and their bioactive
      compounds on oxidative stress.
AB  - Protective effects of sweet orange (Citrus sinensis) peel and their bioactive
      compounds on oxidative stress were investigated. According to HPLC-DAD and HPLC
      MS/MS analysis, hesperidin (HD), hesperetin (HT), nobiletin (NT), and tangeretin
      (TT) were present in water extracts of sweet orange peel (WESP). The cytotoxic
      effect in 0.2mM t-BHP-induced HepG2 cells was inhibited by WESP and their
      bioactive compounds. The protective effect of WESP and their bioactive compounds
      in 0.2mM t-BHP-induced HepG2 cells may be associated with positive regulation of
      GSH levels and antioxidant enzymes, decrease in ROS formation and TBARS
      generation, increase in the mitochondria membrane potential and Bcl-2/Bax ratio,
      as well as decrease in caspase-3 activation. Overall, WESP displayed a
      significant cytoprotective effect against oxidative stress, which may be most
      likely because of the phenolics-related bioactive compounds in WESP, leading to
      maintenance of the normal redox status of cells.

PMID- 22980780
TI  - Quantitative determination of the boar taint compounds androstenone, skatole,
      indole, 3alpha-androstenol and 3beta-androstenol in wild boars (Sus scrofa)
      reveals extremely low levels of the tryptophan-related degradation products.
AB  - The major boar taint compounds androstenone and skatole as well as the minor
      compounds indole, 3alpha-androstenol and 3beta-androstenol were determined in
      back fat samples of 23 male wild boars by applying a recently published SIDA-HS
      SPME-GC/MS method. The boar pheromones androstenone, 3alpha-androstenol and 3beta
      androstenol were found in extraordinary high concentrations, resulting in mean
      values of 3329ng/g androstenone, 1273 ng/g 3alpha-androstenol and 545 ng/g 3beta
      androstenol. Interestingly, skatole was not detectable in about 50% of the boars
      and negligibly low in all other samples as expressed by a mean skatole value of
      only 14 ng/g. Indole was also found in every sample, but again in low
      concentrations with a mean value of 40 ng/g. Possible factors explaining this
      remarkably low skatole deposition in wild boars such as intestinal flora and
      anatomy, dietary composition, housing or genetic predisposition are discussed in
      this paper.

PMID- 22980781
TI  - Physical activity increases the bioavailability of flavanones after dietary
      aronia-citrus juice intake in triathletes.
AB  - Control and triathlete volunteers (n=8 and n=15, respectively) were given 400 mL
      and 200 mL of aronia-citrus juice (AC-juice), respectively. The 24h urine samples
      were hydrolysed to determine the flavanones concentration by UPLC-QqQ-MS/MS. The
      flavanones metabolites in both groups of volunteers were glucuronides, sulfates,
      and sulfo-glucuronides, and the total excretion of flavanones increased fivefold
      in the triathletes compared with the control volunteers. The increase of ninefold
      in the homoeriodictyol of triathletes compared to control volunteers may suggest
      the overactivation of the microbiota metabolism caused by physical exercise. No
      differences concerning the bioavailability were detected between men and women in
      controlboth groups. The AC-juice could provide synergistic effects on health due
      to the increase in the bioavailability of flavanones, avoiding the deleterious
      effects caused by the overdosage of nutritional supplements.

PMID- 22980782
TI  - HPLC-MSn identification and quantification of flavonol glycosides in 28 wild and
      cultivated berry species.
AB  - Berries and red fruits are rich dietary sources of polyphenols with reported
      health benefits. More than 50 different flavonols (glycosides of quercetin,
      myricetin, kaempferol, isorhamnetin, syringetin and laricitrin) have been
      detected and quantified with HPLC-MS(n) in fruits of blueberry, bilberry,
      cranberry, lingonberry, eastern shadbush, Japanese wineberry, black mulberry,
      chokeberry, red, black and white currants, jostaberry, red and white gooseberry,
      hardy kiwifruit, goji berry, rowan, dog rose, Chinese and midland hawthorn, wild
      and cultivated species of blackberry, raspberry, strawberry and elderberry. The
      phenolic constituents and contents varied considerably among the analyzed berry
      species. Elderberry contained the highest amount of total flavonols (450-568
      mgkg(-1) FW), followed by berry species, containing more than 200 mgkg(-1) FW of
      total: chokeberry (267mgkg(-1)), eastern shadbush (261 mgkg(-1)), wild grown
      blackberry (260 mgkg(-1)), rowanberry (232 mgkg(-1)), american cranberry (213
      mgkg(-1)) and blackcurrants (204 mgkg(-1)). Strawberry (10.5 mgkg(-1)) and white
      currants (4.5 mgkg(-1)) contained the lowest amount of total flavonols.
      Quercetins represent the highest percentage (46-100%) among flavonols in most
      analyzed berries. In wild strawberry and gooseberry the prevailing flavonols
      belong to the group of isorhamnetins (50-62%) and kaempferols, which represent
      the major part of flavonols in currants (49-66%). Myricetin glycosides could only
      be detected in chokeberry, rowanberry and species from the Grossulariaceae, and
      Adoxaceae family and Vaccinium genus. Wild strawberry and blackberry contained
      from 3- to 5-fold higher total flavonols than the cultivated one.

PMID- 22980783
TI  - Application of near infrared spectroscopy for the rapid determination of
      antioxidant activity of bamboo leaf extract.
AB  - This study was carried out to evaluate the feasibility of using near infrared
      (NIR) spectroscopy for determining three antioxidant activity indices of the
      extract of bamboo leaves (EBL), specifically 2,2-diphenyl-1-picrylhydrazyl
      (DPPH), ferric reducing/antioxidant power (FRAP), and 2,2'-azinobis-(3-ethylbenz
      thiazoline-6-sulfonic acid) (ABTS). Four different linear and nonlinear
      regressions tools (i.e. partial least squares (PLS), multiple linear regression
      (MLR), back-propagation artificial neural network (BP-ANN), and least squares
      support vector machine (LS-SVM)) were systemically studied and compared in
      developing the model. Variable selection was first time considered in applying
      the NIR spectroscopic technique for the determination of antioxidant activity of
      food or agricultural products. On the basis of these selected optimum
      wavelengths, the established MLR calibration models provided the coefficients of
      correlation with a prediction (r(pre)) of 0.863, 0.910, and 0.966 for DPPH, FARP,
      and ABTS determinations, respectively. The overall results of this study revealed
      the potential for use of NIR spectroscopy as an objective and non-destructive
      method to inspect the antioxidant activity of EBL.

PMID- 22980784
TI  - Simultaneous determination of anthocyanins, coumarins and phenolic acids in
      fruits, kernels and liqueur of Prunus mahaleb L.
AB  - In the fresh tissues of Prunus mahaleb L., three classes of phenolics were
      characterised: phenolic acid derivatives (main compound being o-coumaric acid
      glucoside), quercetin glycosides, and anthocyanins (cyanidin 3,5-diglucoside,
      cyanidin 3-sambubioside, cyanidin 3-xylosyl-rutinoside and cyanidin 3
      rutinoside). Coumarin was also identified. The kernels showed a high content of
      coumarin (0.87 mgg(-1)) which is the main class of metabolites in this sample,
      but present in pitted berries as well (0.63 mgg(-1)). Flavonoids are mainly
      concentrated in the skin and pulp (0.55 mgg(-1)). In 'Mirinello di Torremaggiore'
      liqueur, produced from P. mahaleb L. in accordance with traditional procedures,
      anthocyanins make up 16.5%, phenolic acids 43.3%, coumarin 36.2% and flavonoids
      4% of total compounds. Anthocyanins are the main class in solid residues from
      liqueur production (70%). These findings point out that solid residues of P.
      mahaleb can be considered an interesting and innovative source of appreciable
      amounts of cyanidin glycosides (3.3 mgg(-1)).

PMID- 22980785
TI  - Evaluation the quality characteristics of wheat flour and shelf-life of fresh
      noodles as affected by ozone treatment.
AB  - In this study, the effects of ozone treatment on the microorganism mortality in
      wheat flour and shelf-life of fresh noodles were investigated, as well as the
      physicochemical properties of wheat flour and textural qualities of cooked
      noodles. Results showed that the total plate count (TPC) can be largely reduced
      in wheat flour exposed to ozone gas for 30 min and 60 min. Whiteness of flour and
      noodle sheet, dough stability, and peak viscosity of wheat starch were all
      increased by ozone treatment. Free cysteine content in wheat flour was shown to
      decrease significantly (P<0.05) as the treatment time increased and remarkable
      protein aggregates were observed in both reduced and non-reduced SDS-PAGE
      patterns. In addition, ozone treated noodles were generally higher in firmness,
      springiness, and chewiness, while lower in adhesiveness. Microbial growth and
      darkening rate of fresh noodles made from ozone treated flour were delayed
      significantly.

PMID- 22980786
TI  - Proof-of-concept study of chitosan-based carbon dioxide indicator for food
      packaging applications.
AB  - A chitosan-based carbon dioxide (CO(2)) indicator was developed to monitor
      freshness or quality of packaged foods during their storage, as elevated CO(2)
      levels inside a package is one of the prime indicators of microbial spoilage of
      food. The objective of this proof-of-concept study, therefore, was to develop a
      chitosan-based CO(2) indicator and to investigate its performance in different
      operating environments. For the enhancement of signal strength of indicator, 2
      amino-2-methyl-1-propanol (AMP) was used as an additive to the chitosan solution.
      Aqueous chitosan-AMP suspensions were prepared by addition of chitosan (0.1%,
      0.2% and 0.4%) and AMP (0%, 5%, 10% and 20%) to distilled water at pH 7.0.
      Thereafter, the aqueous chitosan suspensions were incubated under 100% and 20%
      CO(2) test atmospheres. The aqueous solubility of chitosan, which in turn impacts
      the degree of transparency of the suspension, was tested at different pHs and
      time intervals, spectrometrically. The transparency of 0.2% chitosan aqueous
      suspension increased dramatically below pH 6.5 under 20% or 100% CO(2)
      incubation. The addition of a 5% AMP concentration to the chitosan suspension was
      found optimal for maximum CO(2) absorption and this, therefore, increased
      transparency by more than 90%.

PMID- 22980787
TI  - Bioactivity evaluations of ingredients extracted from the flowers of Citrus
      aurantium L. var. amara Engl.
AB  - Citrus aurantium L. var. amara Engl, a member of genus Citrus (Rutaceae),
      widespread in China, is used as folk medicine for the treatment of helping
      digest, phlegm, enteritidis, stomachic and other deceases. In the present
      research, silica gel column, Sephadex LH-20, mass spectrometer (MS) and nuclear
      magnetic resonance (NMR) were used to separate and identify the chemical
      compounds from the flowers of C. aurantium var. amara, and several bioactivity
      assays were used to evaluate their antioxidant, anti-inflammatory, anti-virus and
      antitumour activities. Two major compounds, 5-hydroxy-6,7,3',4'
      tetramethoxyflavone (HTF) and limonexic acid (LA), were isolated and identified
      from C. aurantium var. amara for the first time. The results of the bioactivity
      assays showed that HTF and LA displayed significant antioxidant activities and
      showed significant inhibition effects on the B16 cell lines at a concentration
      range from 6.25 to 50 MUg/ml, and on the SMCC-7721 cell lines from 12.5 to 200
      MUg/ml. The antitumour effect, anti-inflammatory activity and the inhibiting
      expression of HBsAg and HBeAg of 2.2.15 cells displayed the tendency in a
      concentration-dependent manner. These two compounds from C. aurantium var. amara
      could potentially be used as a promising natural agent in the pharmaceutical
      industries.

PMID- 22980788
TI  - Effect of heat treatment on lignification of postharvest bamboo shoots
      (Phyllostachys praecox f. prevernalis.).
AB  - In order to evaluate the effects of heat treatment on the quality of postharvest
      bamboo shoots, the firmness, disease incidence, respiration and ethylene
      production, ACC synthase (ACS) and ACC oxidase (ACO) activities, lignin and
      cellulose contents, and the activities of phenylalanine ammonia-lyase (PAL),
      cinnamyl alcohol dehydrogenase (CAD) and peroxidase (POD) were examined during
      storage at 20 degrees C after heat treatment at 45 degrees C for 5h. Heat
      treatment inhibited disease incidence and respiration, retarded ethylene
      production, and decreased ACS and ACO activities in bamboo shoots. Furthermore,
      heat treatment significantly delayed the rise in the activities of PAL, CAD and
      POD, which were associated with the inhibition of the synthesis of lignin and the
      delayed tissue lignification. These findings suggest that heat treatment could be
      a potential tool to delay lignification and decrease disease incidence in bamboo
      shoots during storage at 20 degrees C.

PMID- 22980789
TI  - Kiwifruit remnants from digestion in vitro have functional attributes of
      potential importance to health.
AB  - The physicochemical properties of plant cell walls in the gut are important in
      modulating processes that influence health. We investigated the physicochemical
      properties of kiwifruit cell walls digested under gastric and gastroileal
      conditions in vitro. Soluble and insoluble undigested polymer fractions were
      measured, the hydration properties of the digested pulp, and the capacity to
      retard diffusion and mixing in a simulated small intestinal segment. Undigested
      polymer (dietary fibre) fractions differed little between "Hayward' ('Hayward')
      and 'Hort16A' (gold) kiwifruit cultivars in their relative proportions, although
      total dietary fibre was greater in 'Hayward' than in the 'Hort16A'. The
      polysaccharide composition of seed-free digestion-resistant polymer was similar
      in both cultivars and not affected by in vitro digestion. Indigestible remnants
      from kiwifruit had strong water retention and swelling capacities, also little
      affected by digesting, and retarded both glucose diffusion and mixing
      significantly, especially in the presence of low background viscosity. We
      conclude that the particulate cell wall remnants of digested kiwifruit retain
      substantial potential to influence the properties of gut contents.

PMID- 22980790
TI  - Green tea extract as food antioxidant. Synergism and antagonism with alpha
      tocopherol in vegetable oils and their colloidal systems.
AB  - The antioxidant effects of alpha-tocopherol (TOH) in combination with green tea
      extract (GTE), the green tea polyphenol (-)-epicatechin (EC) or the isomeric (+)
      catechin (C), were investigated using different lipid systems based on high
      linoleic sunflower oil: bulk oil, o/w-emulsion and a phosphatidylcholine-based
      liposome system. Both polyphenols as well as TOH were efficient antioxidants in
      all systems when used alone, as detected by the formation of free radicals and
      conjugated dienes and by oxygen consumption. Strong synergistic effect was found
      for the combination of TOH and GTE in a methyl linoleate o/w-emulsion and in the
      pure bulk oil, while only an additive effect was observed in a liposome system.
      The synergism was already evident for the tendency for radical formation in the
      bulk oil as detected by electron spin resonance (ESR) spectroscopy. On the
      contrary, combinations of TOH with either EC or C showed clear synergistic
      effects in both heterogeneous systems, but antagonistic or additive effects in
      bulk oil. GTE may accordingly be used to protect both vegetable oils and their
      emulsions against oxidation through enhancement of the activity of their
      endogenous antioxidants, while GTE is less efficient in the protection of
      phospholipids as in liposomes.

PMID- 22980791
TI  - Detection of common vetch (Vicia sativa L.) in Lentil (Lens culinaris L.) using
      unique chemical fingerprint markers.
AB  - Detection of adulteration of split red lentil (Lens culinaris L.) seeds with low
      level addition of split common vetch (Vicia sativa L.) is hampered by a lack of
      reliable detection methods. An analytical method was developed using high
      performance liquid chromatography with diode array detection (HPLC-DAD) based on
      two unique chemical markers found in common vetch: beta-cyanoalanine (BCA) and
      gamma-glutamyl-beta-cyanoalanine (GCA). These two markers were present in samples
      of common vetch seed grown in Canada and Serbia. Authentic lentil samples grown
      in Canada, Australia, USA, Turkey, Syria, and Morocco had no detectable levels of
      these chemical markers. Commercial lentil samples for export from lentil
      processing plants in Saskatchewan, Canada, also had no detectable levels of GCA
      and BCA. The presence of vetch in intentionally adulterated lentil samples could
      be determined via chemical markers with a detection limit of 5% (w/w). The
      proposed method is a simple sample extraction and rapid HPLC analysis that could
      be widely used to detect intentional adulteration of lentils with common vetch.

PMID- 22980792
TI  - Fatty acid profile, trans-octadecenoic, alpha-linolenic and conjugated linoleic
      acid contents differing in certified organic and conventional probiotic fermented
      milks.
AB  - Development of dairy organic probiotic fermented products is of great interest as
      they associate ecological practices and benefits of probiotic bacteria. As
      organic management practices of cow milk production allow modification of the
      fatty acid composition of milk (as compared to conventional milk), we studied the
      influence of the type of milk on some characteristics of fermented milks, such as
      acidification kinetics, bacterial counts and fatty acid content. Conventional and
      organic probiotic fermented milks were produced using Bifidobacterium animalis
      subsp. lactis HN019 in co-culture with Streptococcus thermophilus TA040 and
      Lactobacillus delbrueckii subsp. bulgaricus LB340. The use of organic milk led to
      a higher acidification rate and cultivability of Lactobacillus bulgaricus. Fatty
      acids profile of organic fermented milks showed higher amounts of trans
      octadecenoic acid (C18:1, 1.6 times) and polyunsaturated fatty acids, including
      cis-9 trans-11, C18:2 conjugated linoleic (CLA-1.4 times), and alpha-linolenic
      acids (ALA-1.6 times), as compared to conventional fermented milks. These higher
      levels were the result of both initial percentage in the milk and increase during
      acidification, with no further modification during storage. Finally, use of
      bifidobacteria slightly increased CLA relative content in the conventional
      fermented milks, after 7 days of storage at 4 degrees C, whereas no difference
      was seen in organic fermented milks.

PMID- 22980793
TI  - Determination of volatile nitrosamines in grilled lamb and vegetables using
      comprehensive gas chromatography - nitrogen chemiluminescence detection.
AB  - The grilling of meat may generate dangerous levels of mutagenic and carcinogenic
      nitrosamines (NAs). Meat and vegetable samples underwent a two-step solid-phase
      extraction before analysis by comprehensive gas chromatography with a nitrogen
      chemiluminescence detection system (GCxGC-NCD). The GCxGC-NCD method showed high
      selectivity, sensitivity and equimolarity in its response to six specific NAs. NA
      contamination of charcoal-grilled lamb at various stages of cooking and with
      various fat contents and also charcoal-grilled vegetables were investigated. The
      grilling of lamb on unready charcoal resulted in the formation of considerable
      quantities of NAs. Grilling lamb on properly prepared, ready charcoal resulted in
      an increase in total concentrations of six NAs from 0 to 4.51 MUg kg(-1) over a
      period of 16 min. Increasing the fat content of the grilled lamb from 5% to 20%
      caused a modest increase in total concentrations of the six investigated NAs from
      4.51 to 5.30 MUg kg(-1).

PMID- 22980794
TI  - Decreasing pro-inflammatory cytokine and reversing the immunosenescence with
      extracts of Pu-erh tea in senescence accelerated mouse (SAM).
AB  - Immunosenescence, the progressive decline of adaptive immunity and chronic
      inflammation with ageing has been demonstrated to be the main factor responsible
      for infections, cancer and autoimmune conditions in the elderly. Senescence
      accelerated mouse (SAM) was used to study the protective effects of Pu-erh tea in
      the elderly. The senile-prone sub-strain, SAM-P8 mice were administered
      individually with ripened or crude Pu-erh tea at 125, 250 or 500mg/kg. The
      results showed that Pu-erh tea significantly increased the fractions of naive T
      lymphocytes, CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood,
      but decreased the levels of IL-6 in aged mice. These data suggested that the Pu
      erh tea reversed the immunosenescence by restoring the immune deficiency and
      decreasing pro-inflammatory cytokine. Thus, long term drinking of Pu-erh tea may
      be beneficial for the aged population in terms of increasing the body's
      resistance to infection and cancer.

PMID- 22980796
TI  - A novel trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri).
AB  - Isolation and structural elucidation of a new trans-4-hydroxycinnamic acid
      derivative from Meyer lemon (Citrus meyeri hort. ex Y. Tanaka) was carried out.
      The derivative exhibited the antioxidative activity by ORAC (oxygen radical
      absorbance capacity) assay and was found in the flavedo and alvedo of Meyer lemon
      peel.

PMID- 22980795
TI  - Modified barley straw as a potential biosorbent for removal of copper ions from
      aqueous solution.
AB  - Barley straw (BS), a very low-cost material, has been utilized as a biosorbent
      material for the removal of copper (Cu(2+)) ions from aqueous solutions after
      treatment with citric acid. Barley straw was thermochemically modified with
      citric acid (CA-BS) for the purpose of improving the Cu(2+) ion sorption capacity
      of the straw. Biosorption studies have been carried out to determine the effect
      of pH, adsorbent concentration, contact time, extent of modification, and
      adsorbate concentration on the biosorption capacity of Cu(2+) ions by the
      esterified straw. The equilibrium sorption capacities of Cu(2+) were 4.64 mg/g
      and 31.71 mg/g for BS and CA-BS, respectively. The optimum pH for the removal of
      Cu(2+) ions by CA-BS was around pH 7.0 and the removal of Cu(2+) ions was 88.1%.
      Langmuir, Freundlich, Scatchard and D-R (Dubinin-Radushkevich) isotherms have
      been used to characterize the observed biosorption phenomena of Cu(2+) ions on CA
      BS. The carboxyl groups on the surface of the modified barley straw were
      primarily responsible for the sorption of Cu(2+) ions.

PMID- 22980797
TI  - Early post-mortem sarcoplasmic proteome of porcine muscle related to lipid
      oxidation in aged and cooked meat.
AB  - In order to identify specific markers of lipid oxidation generated in meat during
      refrigerated storage and cooking an analysis was conducted to investigate the
      relationships between the early post-mortem sarcoplasmic proteome, which contains
      the majority of enzymes involved in the oxidative process, and the level of lipid
      oxidation. This study was performed in Longissimus lumborum pig muscle. Proteome
      was analysed by 2-D electrophoresis in combination with liquid chromatography
      tandem mass spectrometry (LC-MS/MS) and lipid oxidation was estimated by the TBA
      reactive substances (TBA-RS) measurement. Many markers of lipid oxidation were
      identified, but no single marker covered the oxidative process in its entirety.
      The role of five protein groups (albumin, redoxins, annexins, lipid transporters
      and enzymes of aerobic respiration), from which a link with lipid oxidation can
      be established, is discussed. This study, which completes a precedent work
      focused on protein oxidation, clearly demonstrates that a combination of several
      markers is needed to assess the sensitivity of meat to oxidation during both
      ageing and cooking.

PMID- 22980798
TI  - Effect of high pressure treatment on ovotransferrin.
AB  - High pressure processing of ovotransferrin was carried out to study the
      structural and physiochemical changes of ovotransferrin under various pressure
      levels. At pH 8 and pressures higher than 200 MPa, a decrease in total sulfhydryl
      groups and an increase in surface hydrophobicity were observed along with a
      partial aggregation. A gradual shift of denaturation peak towards higher
      temperature was noticed up to 500 MPa, leading to a total loss of the enthalpy of
      denaturation at pressures of 600 and 700 MPa, where a significant decrease in
      intrinsic fluorescence was also observed. At pH 3, the ovotransferrin adopted a
      molten globule state, associated with a significant increase in surface
      hydrophobicity and reactive sulfhydryl content; structurally, no clear
      denaturation peaks in differential scanning calorimetry (DSC) were detected at
      any level of pressure treatment whereas a noticeable decrease in intrinsic
      fluorescence was evidenced up to 600 MPa and then increased at 700 MPa pressure
      treatment. Fourier transform infrared spectroscopy (FT-IR) revealed that the
      conformational structure were changed from helices, sheets, turns, and aggregated
      strand to mostly intermolecular beta-sheets or aggregated strands at pH 8 at 200
      MPa but switched back to original structure at higher pressures.

PMID- 22980799
TI  - Enzymatic bioconversion of citrus hesperidin by Aspergillus sojae naringinase:
      enhanced solubility of hesperetin-7-O-glucoside with in vitro inhibition of human
      intestinal maltase, HMG-CoA reductase, and growth of Helicobacter pylori.
AB  - Hesperetin-7-O-glucoside (Hes-7-G) was produced by the enzymatic conversion of
      hesperidin by Aspergillus sojae naringinase due to the removal of the terminal
      rhamnose. Extracts from orange juice and peel containing the hesperidin were so
      treated by this enzyme that the hesperidin could also be converted to Hes-7-G.
      The solubility of Hes-7-G in 10% ethanol was enhanced 55- and 88-fold over those
      of hesperidin and hesperetin, respectively, which may make Hes-7-G more
      bioavailable. Hes-7-G was 1.7- and 2.4-fold better than hesperidin and
      hesperetin, respectively, in the inhibition of human intestinal maltase. Hes-7-G
      was more potent by 2- and 4-fold than hesperidin in the inhibition of human HMG
      CoA reductase. Additionally, Hes-7-G exhibited more effective inhibition of the
      growth of Helicobacter pylori than hesperetin, while its effectiveness was
      similar to that of hesperidin. Therefore, the results suggest that bioconverted
      Hes-7-G is more effective and bioavailable than hesperidin, as it has enhanced
      inhibitory and solubility properties.

PMID- 22980800
TI  - Comparison of the properties of multi-composite fish gelatin films with that of
      mammalian gelatin films.
AB  - Four types of films viz. gelatin, gelatin-MMT, gelatin-chitosan and gelatin-MMT
      chitosan prepared from redsnapper and grouper bone gelatin were compared with the
      mammalian gelatin films, for their mechanical and barrier properties. Grouper
      gelatin films had higher tensile strength (TS) and Young's modulus (YM), but
      lower elongation at break (EAB) than redsnapper films. Incorporation of MMT and
      chitosan improved the TS (p<0.05) of the films. Water solubilities were lower
      (p<0.05) in films incorporated with chitosan compared to simple gelatin film.
      Protein solubilities were lower in gelatin-MMT films, irrespective of the type of
      solvent used. The water vapour transmission rates (WVTR) of fish and mammalian
      gelatin films were similar, but addition of MMT had reduced WVTR (p<0.05). SEM
      micrographs depicted smoother surface for gelatin-MMT and gelatin-MMT-chitosan
      films. Thus, composite fish gelatin films made with MMT and chitosan could be the
      good natural biodegradable films due to their better mechanical and barrier
      properties.

PMID- 22980801
TI  - Characterisation of volatile and non-volatile metabolites in etiolated leaves of
      tea (Camellia sinensis) plants in the dark.
AB  - Aroma is an essential factor affecting the quality of tea (Camellia sinensis)
      products. While changes of volatile compounds during tea manufacturing have been
      intensively studied, the effect of environmental factors on volatile contents of
      fresh tea leaves has received less attention. We found that C. sinensis var.
      Yabukita kept in darkness by shading treatment for 3 weeks developed etiolated
      leaves with significantly increased levels of volatiles, especially volatile
      phenylpropanoids/benzenoids (VPBs). Upstream metabolites of VPBs, in particular
      shikimic acid, prephenic acid, and phenylpyruvic acid, showed lower levels in
      dark treated than in control leaves, whereas the contents of most amino acids
      including l-phenylalanine, a key precursor of VPBs, were significantly enhanced.
      In addition, analysis by ultra performance liquid chromatography-time of flight
      mass spectrometry, capillary electrophoresis-time of flight mass spectrometry,
      high performance liquid chromatography, and gas chromatography-mass spectrometry
      indicated that volatile and non-volatile metabolite profiles differed
      significantly between dark treated and untreated leaves.

PMID- 22980802
TI  - Simultaneous determination of iridoid glycosides, phenethylalcohol glycosides and
      furfural derivatives in Rehmanniae Radix by high performance liquid
      chromatography coupled with triple-quadrupole mass spectrometry.
AB  - In this study, a sensitive and selective method for simultaneously quantifying
      eight major components (four iridoid glycosides, three phenethylalcohol
      glycosides and one furfural derivative) of Rehmanniae Radix by high performance
      liquid chromatography coupled with triple-quadrupole mass spectrometry (HPLC-TQ
      MS) was developed. The sample preparation was executed using an optimised
      ultrasonic method with complete extraction efficiencies of eight analytes. For
      mass spectrometry, selected ion recording (SIR) scan mode was used to improve the
      sensitivity and selectivity. The established method was validated in terms of
      linearity, sensitivity, precision, accuracy and stability, and successfully
      applied to determine the contents of the eight analytes in different batches of
      raw and processed Rehmanniae Radix, which confirmed that the established method
      was reliable and useful for "holistic" quality evaluation of Rehmanniae Radix.
      The quantitative results indicated that the quality of commercial raw or
      processed Rehmanniae Radix was remarkably inconsistent.

PMID- 22980803
TI  - Binding of polyphenols to plant cell wall analogues - Part 2: Phenolic acids.
AB  - Bacterial cellulose and cellulose-pectin composites were used as well-defined
      model plant cell wall (PCW) systems to study the interaction between phenolic
      acids (PA) derived from purple carrot juice concentrate (PCJC) and PCW
      components. Significant PA depletion from solution occurred, with pure cellulose
      initially (30s-1h) absorbing more than cellulose-pectin composites in the first
      hour (ca 20% cf 10-15%), but with all composites absorbing similar levels (ca
      30%) after several days. Individual PAs bound to different relative extents with
      caffeic acid>chlorogenic acid>ferulic acid. Extrapolation of data for these model
      systems to carrot puree suggests that nutritionally-significant amounts of PAs
      could bind to cell walls, potentially restricting bioavailability in the small
      intestine and, as a consequence, delivering PAs to the large intestine for
      fermentation and metabolism by gut bacteria.

PMID- 22980804
TI  - Mitigating effect of amaranth (Amarantus hypochondriacus) protein on acrylamide
      formation in foods.
AB  - The effect of addition of amaranth flour and amaranth protein isolate to both a
      glucose/asparagine model system and real foods (cookies, fried tortilla chips,
      and baked tortilla chips) was studied to analyse the acrylamide mitigating
      potential of this underexploited plant with attractive nutraceutical properties.
      Addition of amaranth flour, with a relatively low protein content (16.45%), did
      not mitigate acrylamide in either the model system or the studied foods. On the
      contrary, addition of amaranth protein isolate decreased acrylamide content by 35
      40% in the model system, 89% in cookies, 51% in fried tortilla chips, and 62% in
      baked tortilla chips. This acrylamide reduction was obtained without change in
      the colour or the texture of the cookies. On the contrary, colour remained
      unchanged in tortilla chips, but the addition of amaranth protein isolate
      increased the hardness (16-36%) of the produced tortillas. Although a much more
      detailed sensory evaluation of cookies and tortilla chips prepared using amaranth
      protein isolate is needed, the above results suggest that the use of amaranth
      protein may be an interesting way to both mitigate acrylamide formation and
      improve nutritional properties of foods.

PMID- 22980805
TI  - Optimization of ionic liquid based ultrasonic assisted extraction of puerarin
      from Radix Puerariae Lobatae by response surface methodology.
AB  - Ionic liquid (IL) based ultrasonic assisted extraction (ILUAE) was developed for
      the effective extraction of puerarin from Radix Puerariae Lobatae (RPL). The
      ILUAE parameters including the type of ILs, IL concentration, RPL amount,
      ultrasonic power and time were optimized by single-factor experiment and response
      surface methodology. Under the optimized experimental conditions, the best
      results were obtained using RPL amount 0.43 g in 10 mL 1.06 molL(-1) 1-butyl-3
      methylimidazolium bromide aqueous solution, ultrasonic time 27.43 min and
      ultrasonic power 480 W. Scanning electron microscope images of RPL samples were
      obtained to provide visual evidence of the sonication effect. Compared with the
      conventional ultrasonic assisted extraction and refluent extraction, the proposed
      ILUAE offered shorter extraction time and remarkable higher efficiencies due to
      the higher penetration ability and solubility of IL and the cavitation phenomenon
      produced in the solvent by the passage of an ultrasonic wave, which further
      supported the suitability of the proposed approach.

PMID- 22980806
TI  - Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and
      CYP 3A.
AB  - Liquorice (root of Glycyrrhiza uralensis FISCH) is an ingredient of candies and
      used as a popular medicine in Europe and oriental countries. Cyclosporine (CsA),
      an immunosuppressant with narrow therapeutic window, is widely used in transplant
      patients. The absorption and disposition of CsA were associated with P
      glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the
      effects of liquorice extract (LE) and its major ingredient, glycyrrhizin (GZ), on
      CsA pharmacokinetics in rats. The results indicated that LE and GZ significantly
      decreased the peak blood concentration and the areas under the curves of CsA in
      rats. Mechanism studies revealed that glycyrrhetic acid (GA), the major
      metabolite of GZ, significantly activated the functions of P-gp and CYP3A4. In
      conclusion, liquorice significantly reduced the oral bioavailability of CsA
      through activating P-gp and CYP3A4.

PMID- 22980807
TI  - Detection of irradiated frog (Limnonectes macrodon) leg bones by multifrequency
      EPR spectroscopy.
AB  - The free radicals of irradiated frog Limnonectes macrodon leg bones tissue were
      studied by electron paramagnetic resonance in both X and Q bands. The kinetic
      behaviour, the activation energy as well as the thermal stability of the
      radiation-induced radicals in bone tissue were investigated by means of both
      isothermal and isochronal annealing. Unirradiated bone tissue displayed the
      presence of Mn(2+) ions at both frequencies, while a week EPR singlet was
      evidenced only at 34 GHz. When irradiated with (60)Co gamma ray, the EPR spectra
      completely changed their patterns and intensity, the overall spectra provin, at
      both frequencies, to be typical axial ones. The 100 degrees C isothermal
      annealing studies attested the existence of two different free radical species,
      significantly more labile than in the case of mammal bone tissues. At the same
      time, the Arrhenius plot of 15 kGy irradiated bones evidenced two different
      kinetic regimes with two different activation energies.

PMID- 22980808
TI  - Antihypertensive properties of flavonoid-rich apple peel extract.
AB  - Hypertension is a major public health problem rising across the globe. Inhibition
      of angiotensin converting enzyme (ACE) is identified as a main therapeutic target
      in controlling high blood pressure. The present study investigated the ACE
      inhibitory property of a flavonoid-rich apple peel extract (FAE), its
      constituents, selected flavonoids and some quercetin metabolites using a
      biochemical assay of ACE inhibition and a human umbilical vein endothelial cell
      (HUVEC) model. FAE, all the tested flavonoids except genistein, and two quercetin
      metabolites (quercetin-3-O-glucuronic acid and quercetin-3-O-sulfate)
      significantly (p<0.05) inhibited ACE. Enzyme kinetic analysis revealed that
      flavonoids are competitive inhibitors of ACE. In the HUVEC model, FAE, quercetin
      3-O-glucoside and quercetin-3-O-glucuronic acid inhibited significantly (p<0.05)
      ACE activity. Overall, FAE and most of the flavonoids tested showed ACE
      inhibition in vitro which needs further investigations using animal and human
      clinical trials.

PMID- 22980809
TI  - Isoamylacetate production by entrapped and covalently bound Candida rugosa and
      porcine pancreatic lipases.
AB  - Candida rugosa lipase (CRL) and porcine pancreatic lipase (PPL) were immobilised
      by entrapping and also by covalent binding for use in synthesis of isoamyl
      acetate (IAAc), which has a typical banana flavour. Lipase entrapment was carried
      out by dripping sodium alginate (Na-Alg)-chitosan (Chi)-lipase mixture into
      CaCl(2)-glutaraldehyde (GAL) solution to obtain Ca-Alg/Chi(CRL/PPL).
      Immobilisation conditions were optimised as 1.5% Na-Alg, 1.5% chitosan and 0.15%
      GAL. Ca-Alg/Chi(CRL/PPL) samples showed the highest activity when they were dried
      upon reaching 27% of their initial weights. Covalent binding was achived with Chi
      modified with spacerarm via glutaraldehyde to get Chi(CRL/PPL). The highest IAAc
      production was observed when 1,3-diaminopropane was used as a spacer arm. The
      best ester yield was achieved in heptane, at 40 and 45 degrees C reaction
      temperatures, 50mM IAA and 50 or 75 mM AA concentrations. The amount of IAAc was
      nearly 10 times higher for the batch type than for the continuous packed bed
      column reactor.

PMID- 22980810
TI  - Influence of fatty acid composition on chemical changes in blends of sunflower
      oils during thermoxidation and frying.
AB  - The influence of fatty acid composition on formation of new compounds at frying
      temperatures has been studied in seven samples of sunflower oils widely differing
      in their fatty acid composition. Thermal oxidation assays as well as frying
      experiments were carried out and samples were evaluated by measuring the new
      compounds formed, i.e. polymers, polar compounds and their distribution by
      molecular weight, and polar fatty acids and their distribution by molecular
      weight. The levels of all the new compounds analysed strongly depended on the
      degree of oil unsaturation; the two least unsaturated oils with low content of
      linoleic acid and high content of palmitic acid behaved exceptionally well. When
      considering polar compounds or polar fatty acids, the polymers/oxidised monomers
      ratio increased significantly as the level of degradation increased. The new
      compounds formed are practically identical when analysed in the used frying oils
      or in the lipids extracted from the counterpart fried potatoes, independently of
      the level of degradation.

PMID- 22980811
TI  - Varietal and pre-fermentative volatiles during ripening of Vitis vinifera cv
      Nebbiolo berries from three growing areas.
AB  - Flavour analysis of grape is a key step in quality evaluation. The Stir Bar
      Sorptive Extraction technique (SBSE, 'Twister'(r)) was used to assess varietal
      and pre-fermentative volatile accumulation in 'Nebbiolo' berries, from veraison
      to harvest. Grapes were collected in three vineyards, representing different
      'crus' in the cultivation areas of Barolo, Barbaresco and Roero (North-West
      Italy). Volatile constituents of grapes were identified and quantified by GC-MS.
      We demonstrate the influence exerted by the growing location on volatile
      concentration and profile, as well as on the timing of volatile accumulation. The
      accumulation of certain classes of compounds, considered favourable for defining
      berry quality, followed common patterns, and was negatively correlated to that of
      compounds with herbaceous and grassy notes, such as the C6 compounds. PCA
      analysis shows that the concentrations of varietal and pre-fermentative volatiles
      were more effective in separating growing areas than dates of harvest. Grapes
      from the Barbaresco area, showing higher values of the concentration ratio
      between favourable and unfavourable compounds throughout ripening, could be
      statistically separated from grapes from the other areas.

PMID- 22980812
TI  - Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in
      muscle cells via multipathway mechanisms.
AB  - Saffron (Crocus sativus Linn.) has been an important subject of research in the
      past two decades because of its various biological properties, including anti
      cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other
      hand, the molecular bases of its actions have been scarcely understood. Here, we
      elucidated the mechanism of the hypoglycemic actions of saffron through
      investigating its signaling pathways associated with glucose metabolism in
      C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the
      phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA
      carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase
      (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron
      and insulin further improved the insulin sensitivity via both insulin-independent
      (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways.
      It also suggested that there is a crosstalk between the two signaling pathways of
      glucose metabolism in skeletal muscle cells. These results could be confirmed
      from the findings of GLUT4 translocation. Taken together, AMPK plays a major role
      in the effects of saffron on glucose uptake and insulin sensitivity in skeletal
      muscle cells. Our study provides important insights for the possible mechanism of
      action of saffron and its potential as a therapeutic agent in diabetic patients.

PMID- 22980813
TI  - Phycobiliproteins or C-phycocyanin of Arthrospira (Spirulina) maxima protect
      against HgCl(2)-caused oxidative stress and renal damage.
AB  - Our objective was to determine if the phycobiliproteins of Arthrospira
      (Spirulina) maxima protect renal cells against mercury-caused oxidative stress
      and cellular damage in the kidney. We used 40 male mice that were assigned into
      eight groups: (1) a control group that received 100mM phosphate buffer (PB) ig
      and 0.9% saline ip, (2) PB+HgCl(2) (5mg/kg ip), (3) PB plus phycobiliproteins
      (100mg/kg ig), (4) PB plus C-phycocyanin (100mg/kg ig), and four groups receiving
      HgCl(2)+phycobiliproteins or C-phycocyanin (50, and 100mg/kg ig). The left
      kidneys were used to determine lipid peroxidation, quantification of reactive
      oxygen species, and reduced glutathione and oxidised content. The right kidneys
      were processed for histology. The HgCl(2) caused oxidative stress and cellular
      damage. All doses of phycobiliproteins or C-phycocyanin prevented enhancement of
      oxidative markers and they protected against HgCl(2)-caused cellular damage.

PMID- 22980814
TI  - Screening natural antioxidants in peanut shell using DPPH-HPLC-DAD-TOF/MS
      methods.
AB  - Peanut shell, a byproduct in oil production, is rich in natural antioxidants.
      Here, a rapid and efficient method using DPPH-HPLC-DAD-TOF/MS was used for the
      first time to screen antioxidants in peanut shell. The method is based on the
      hypothesis that upon reaction with 1, 1-diphenyl-2-picrylhydrazyl (DPPH), the
      peak areas of compounds with potential antioxidant activities in the HPLC
      chromatogram will be significantly reduced or disappeared, and the identity
      confirmation could be achieved by HPLC-DAD-TOF/MS technique. With this method,
      three compounds possessing potential antioxidant activities were found abundantly
      in the methanolic extract of peanut shell. They were identified as 5,7
      dihydroxychromone, eriodictyol, and luteolin. The contents of these compounds
      were 0.59, 0.92, and 2.36 mg/g, respectively, and luteolin possessed the
      strongest radical scavenging capacity. DPPH-HPLC-DAD-TOF/MS assay facilitated
      rapid identification and determination of natural antioxidants in peanut shell,
      which may be helpful for value-added utilization of peanut processing byproducts.

PMID- 22980815
TI  - Determination of element contents in herbal drugs: chemometric approach.
AB  - The elemental content of 23 commercial herbal drugs was evaluated and
      multivariate analysis such as principal component analysis (PCA) and hierarchical
      cluster analysis (HCA) were performed with aim to know the relationship among the
      elements in the herbal drugs. Among the 13 elements investigated K (8096.97), Na
      (581.53), Cu (2.06); Mg (678.4); Fe (476.93), Al (321.5), Co (0.22); Zn (4.46),
      Ni (0.56); Mn (25.77); Pb (13.33); and Cr (13.18)mg/kg dry weight, respectively,
      were found at high concentrations in Eclipta prostrata; Adhatoda vasica;
      Phyllanthus amarus; Hybanthus enneaspermus; Cardiospermum halicacabum; Acacia
      nilotica; and Denolix elata. Interestingly, the toxic element Cd was below
      detectable level in all the samples and Cr, Pb and Ni were lower than the
      permissible limit as prescribed by the World Health Organisation (WHO). This
      study clearly shows that PCA and HCA procedures appear useful tools for the
      differentiation and classification of herbal drugs using the profile of elements.

PMID- 22980816
TI  - Evaluation of cardiovascular protective effect of different apple varieties -
      Correlation of response with composition.
AB  - Epidemiological evidence supports the concept that diets rich in fruits and
      vegetables promote health and attenuate or delay the onset of cardiovascular
      disease (CVD). In particular, a reduced risk of CVD has been associated with
      apple consumption, probably due to the cholesterol-lowering effect of the main
      bioactive compounds, namely fibre and polyphenols. In this work, the effect of
      diet supplementation with 20% of three Portuguese apple cultivars (Bravo de
      Esmolfe, Malapio Serra and Golden), containing distinct phenolic and fibre
      concentrations, on serum lipid profile and oxLDL of male Wistar rats fed a
      cholesterol-enriched diet (2%) was evaluated. After 30 days, only Bravo de
      Esmolfe apple was able to decrease significantly serum levels of triglycerides,
      total and LDL cholesterol concentrations (reductions of 27.2%, 21.0% and 20.4%,
      respectively, in relation to the cholesterol-enriched diet group, P<0.05). The
      levels of oxLDL were also significantly improved with the consumption of this
      apple variety (reductions of 20.0% and 11.9%, in relation to the cholesterol
      enriched diet group and control group, respectively, P>0.05) as well as with
      Malapio da Serra apple (reductions of 9.8% in relation to the cholesterol
      enriched diet group, P<0.05). Correlation of the bioactive response with chemical
      composition showed that catechin, epicatechin, procyanidin B1 and beta-carotene
      are the major phytocompounds responsible for the cholesterol lowering ability of
      apples. The antioxidant potential may have also contributed to this beneficial
      effect.

PMID- 22980817
TI  - A novel method for determining vitamin B1 in a wide variety of foodstuffs with or
      without polyphenols.
AB  - Certain foodstuffs exhibit matrix interference effects on the vitamin B(1)
      analysis prescribed in the official methods of the European Union, AOAC
      International, and Japan. In this study, we demonstrated that one of the
      problematic polyphenols in green tea or cocoa was tannin. For these matrices,
      thiamine was found to interact with tannin in the extraction step and was thus
      removed by filtration as a residue. To resolve the matrix interference, we
      proposed lowering the pH of the extraction solution by adding hydrochloric acid
      after the enzyme reaction. High precision (2-3% RSDr) and good recovery (98.3
      103%) were obtained with reference materials using the proposed method. We also
      confirmed the equivalence of the obtained data from the proposed method and the
      Japanese official method for nutritional labeling. From these results, the method
      was found to be effective for vitamin B(1) analysis regardless of the presence of
      interference matrices.

PMID- 22980818
TI  - Quantification of lactose using ion-pair RP-HPLC during enzymatic lactose
      hydrolysis of skim milk.
AB  - The correct labelling of dairy foods as "lactose-free" requires a suitably
      sensitive and valid analytical method for the quantification of lactose in
      complex food matrices. Thus, an ion-pair RP-HPLC method for the simultaneous
      determination of lactose, glucose and galactose in original skim milk was
      investigated. The samples derived from an enzymatic lactose hydrolysis approach
      (0.5L) using the commercial beta-galactosidase Godo-YNL2. After derivatisation
      with p-aminobenzoic acid and sodium cyanoborohydride, the samples were injected
      on a RP-C(18) column. Tetrabutylammonium hydrogen sulphate was used as the ion
      pair reagent in the eluent system. The sugars were quantified using photometric-
      (UV; 303 nm) and fluorescence-detection (lambda(ex) 313 nm, lambda(em) 358 nm).
      The overall run time was 27 min. The limits of detection (LOD) were estimated at
      2 mgL(-1) (UV detection) and at 0.13 mgL(-1) (fluorescence detection). The limits
      of quantification were 6 mgL(-1) (UV detection) and 0.45 mgL(-1) (fluorescence
      detection). Thus, this analytical method is suitable for sensitive lactose
      quantification in milk systems of less than 10 mgL(-1).

PMID- 22980819
TI  - Influence of alanine uptake on Staphylococcus aureus surface charge and its
      susceptibility to two cationic antibacterial agents, nisin and low molecular
      weight chitosan.
AB  - Low molecular weight chitosan (LMWC) and nisin, recognized as cationic
      antibacterial agents (CAAs), inhibit bacterial growth by interacting with the
      anionically charged cell wall. In this study, alanine uptake significantly
      reduced the anionic cell surface charge, as determined by the zeta potential (ZP)
      measurements, of Staphylococcus aureus, resulting from the incorporation of d
      alanine into the cell wall. Minimum inhibitory concentration (MIC) tests and
      growth inhibition curves revealed that LMWC and nisin possessed inverse
      antibacterial activity against three strains of S. aureus, depending on the
      strains' net charge. A twofold reduction in the MIC value of nisin was obtained
      against S. aureus, inoculated in a 1.0% d- or l-alanine-augmented trypticase soy
      broth medium. A flocculation test demonstrated that neutralizing the anionic
      surface charge using d-alanine reduced the adsorption of S. aureus onto LMWC.
      Furthermore, the reduced surface net charge could enhance the colonization
      capacity of S. aureus on glass.

PMID- 22980820
TI  - Antiradical activity of different parts of Walnut (Juglans regia L.) fruit as a
      function of genotype.
AB  - The objective of this work was to analyse phenolic compounds and antiradical
      capacity of different parts of walnut fruit among six genotypes of Juglans regia
      L. Therefore, total phenolic and flavonoid content were determined and methanolic
      extracts of walnut genotypes were considered by the reducing power, DPPH (2,2
      diphenyl-1-picrylhydrazyl), superoxide anion and nitric oxide radical scavenging.
      Significant differences were found in phenolic content and radical scavenging
      capacity of different parts of fruits and among various genotypes. High
      correlation coefficient (R(2)=0.81) was observed between phenol content and
      radical scavenging activity, but this was not always true (R(2)=0.01). These
      results demonstrated that walnut genotypes have different phenolic compounds and
      phenolic compounds have different radical scavenging power. The differences of
      phenolic compounds were confirmed by using high performance liquid chromatography
      (HPLC).

PMID- 22980821
TI  - Rapid determination of cholesterol in milk containing emulsified foods.
AB  - In this study, a rapid and easy sample preparation method that involved no
      heating saponification and dSPE (dispersive solid phase extraction) clean-up was
      developed to determine the level of cholesterol in milk containing emulsified
      foods (infant formula, baby food, cheese). The developed method utilised high
      performance liquid chromatography with an ultraviolet detector (HPLC-UVD) as a
      separation instrument. The optimum extraction conditions were determined as 10 mL
      isopropyl alcohol with 8.0 g (NH(4))(2)SO(4) per 1g sample, and saponification
      was achieved using 25mg KOH, 1.6g NaCl and 100mg of a silica based NH(2).
      Cholesterol levels determined using CRMs (NIST SRM 1849 and 1544) were in the
      range of the certificated value and the recovery test using spiked materials
      ranged from 94.34% to 102.34% with a RSD of 0.63-4.10%. This method enables the
      accurate determination of cholesterol with reduced sample preparation time.

PMID- 22980822
TI  - Interactions of different polyphenols with bovine serum albumin using
      fluorescence quenching and molecular docking.
AB  - Polyphenols are responsible for the major organoleptic characteristics of plant
      derived foods and beverages. Here, we investigated the binding of several
      polyphenols to bovine serum albumin (BSA) at pH 7.5 and 25 degrees C: catechins
      [(-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3
      gallate], flavones (kaempferol, kaempferol-3-glucoside, quercetin, naringenin)
      and hydroxycinnamic acids (rosmarinic acid, caffeic acid, p-coumaric acid).
      Fluorescence emission spectrometry and molecular docking were applied to compare
      experimentally determined binding parameters with molecular modelling. Among
      these polyphenols, (-)-epicatechin-3-gallate showed the highest Stern-Volmer
      modified quenching constant, followed by (-)-epigallocatechin-3-gallate.
      Similarly, (-)-epicatechin-3-gallate had the highest effect on the Circular
      Dichroic spectrum of BSA, while the changes induced by other polyphenols were
      negligible. Molecular docking predicted high binding energies for (-)-epicatechin
      3-gallate and (-)-epigallocatechin-3-gallate for the binding site on BSA near
      Trp213. Our data reveal that the polyphenol structures significantly affect the
      binding process: the binding affinity generally decreases with glycosylation and
      reduced numbers of hydroxyl groups on the second aromatic ring.

PMID- 22980823
TI  - Isolation, identification and quantification of unsaturated fatty acids, amides,
      phenolic compounds and glycoalkaloids from potato peel.
AB  - Eleven compounds were isolated from potato peels and identified. Their structures
      were determined by interpretation of UV, MS, 1D, and 2D NMR spectral data and by
      comparison with reported data. The main components of the potato peels were found
      to be chlorogenic acid and other phenolic compounds, accompanied by 2
      glycoalkaloids, 3 low-molecular-weight amide compounds, and 2 unsaturated fatty
      acids, including an omega-3 fatty acid. The potato peels showed more potent
      radical scavenging activity than the flesh. The quantification of the 11
      components indicated that the potato peels contained a higher amount of phenolic
      compounds than the flesh. These results suggest that peel waste from the industry
      of potato chips and fries may be a source of useful compounds for human health.

PMID- 22980824
TI  - Increase in antioxidant effect of ginsenoside Re-alanine mixture by Maillard
      reaction.
AB  - Ginsenoside Re, one of the major triol type ginsenosides contained in Panax
      ginseng, has a hydrophobic four-ring steroid-like structure with hydrophilic
      sugar moieties at carbon-3 and -20. The aim of the present study was to identify
      the changes in structure and antioxidant activity of ginsenoside Re by the
      Maillard reaction, which has not been reported yet. The free radical-scavenging
      activity of ginsenoside Re-alanine mixture was increased by heat-processing.
      Ginsenoside Re was gradually changed into Rg(2), Rg(6) and F(4) by heat
      processing, and the glucosyl moiety at carbon-20 was separated. The improved-free
      radical-scavenging activity by heat-processing was mediated by the generation of
      antioxidant Maillard reaction products (MRPs). Antioxidant MRPs were generated
      from the reaction of glucose and alanine. Based on the viability results of LLC
      PK1 renal epithelial cells, MRPs and less-polar ginsenosides contributed to the
      combined renoprotective effect against oxidative renal damage. Maillard reaction
      is importantly involved in the increased antioxidant effect of ginsenoside by
      heat-processing.

PMID- 22980825
TI  - Degradation of curdlan using hydrogen peroxide.
AB  - Curdlan, a linear glucan interconnected by beta-(1->3) linkages, is soluble in
      alkaline solutions but not in water, which limits its wide application,
      particularly in the food industry. In this study, curdlan was subjected to
      oxidative degradation using hydrogen peroxide (H(2)O(2)). The optimal hydrolysis
      conditions were determined, and the results were as follows: reaction time, 40
      min; temperature, 60 degrees C; H(2)O(2) concentration, 1.5% (v/v); and NaOH
      concentration, 2.5M. Under these optimised conditions, the maximum dextrose
      equivalent value (13.49%) was obtained. The composition and the structure of the
      hydrolysates were characterised by high-performance liquid chromatography and
      Fourier-transform infra-red spectroscopy, respectively. The hydrolysates were
      filtered, neutralised with HCl, concentrated to ~12% (w/v), desalted, and freeze
      dried to yield a water-soluble, white powder. The (1->3)-beta-d-glucan
      oligosaccharide content of the product was 98.6% and the yield was 91.4% (w/w).

PMID- 22980826
TI  - Rapid method for controlling the correct labeling of products containing common
      octopus (Octopus vulgaris) and main substitute species (Eledone cirrhosa and
      Dosidicus gigas) by fast real-time PCR.
AB  - The TaqMan real-time PCR has the highest potential for automation, therefore
      representing the currently most suitable method for screening, allowing the
      detection of fraudulent or unintentional mislabeling of species. This work
      describes the development of a real-time polymerase chain reaction (RT-PCR)
      system for the detection and identification of common octopus (Octopus vulgaris)
      and main substitute species (Eledone cirrhosa and Dosidicus gigas). This
      technique is notable for the combination of simplicity, speed, sensitivity and
      specificity in an homogeneous assay. The method can be applied to all kinds of
      products; fresh, frozen and processed, including those undergoing intensive
      processes of transformation. This methodology was validated to check how the
      degree of food processing affects the method and the detection of each species.
      Moreover, it was applied to 34 commercial samples to evaluate the labeling of
      products made from them. The methodology herein developed is useful to check the
      fulfillment of labeling regulations for seafood products and to verify
      traceability in commercial trade and for fisheries control.

PMID- 22980827
TI  - Volatile composition of partially fermented wines elaborated from sun dried Pedro
      Ximenez grapes.
AB  - In this work, we used a cell immobilisation system consisting of Penicillium
      chrysogenum fungi (GRAS) bound to the osmotolerant yeast strains Saccharomyces
      cerevisiae X4 and X5 for the partial fermentation of raisin musts. The resulting
      wines were compared with others obtained by partial fermentation of musts with
      free yeasts and with a traditionally produced sweet wine (i.e. without
      fermentation of the must). The analysis of volatile compounds grouped by aroma
      series showed the partially fermented musts had a more complex aroma than the
      traditional wine. Specially prominent among aroma series was that of ripe fruit,
      followed by the milky and chemical series. The volatiles with the greatest impact
      on wine aroma as assessed in terms of odour activity were ethyl hexanoate, ethyl
      octanoate, butyrolactone, isoamyl alcohols, acetaldehyde, ethyl acetate, 2,3
      butanediol, acetoin and 2,3-butanedione. A cluster analysis according to the Ward
      method was performed to assess the similarity between the traditional sweet wine
      and those obtained by partial fermentation with free and immobilised yeasts
      revealed small differences between the wines obtained with free and immobilised
      yeasts, and marked differences between partially fermented and traditionally
      obtained sweet wine. The wines provided by immobilised yeasts were the most
      appreciated in the sensory analysis (especially those obtained with X4 yeasts).

PMID- 22980828
TI  - Increased significance of food wastes: selective recovery of added-value
      compounds.
AB  - A single-step selective separation of two food additives was investigated using
      alcohol-salt aqueous two-phase systems (ATPS). The selective partitioning of two
      of the most used additives from a processed food waste material, vanillin and l
      ascorbic acid, was successfully accomplished. The results obtained prove that
      alcohol-salt ATPS can be easily applied as cheaper processes for the selective
      recovery of valuable chemical products from food wastes and other sources. As a
      first approach, the phase diagrams of ATPS composed of different
      alcohol+inorganic salt+water were determined at 298 (+/- 1)K and atmospheric
      pressure. The influence of methanol, ethanol, 1-propanol, and 2-propanol and
      K(3)PO(4), K(2)HPO(4) or KH(2)PO(4)/K(2)HPO(4) in the design of the phase
      diagrams was addressed. After the evaluation of the phase diagrams behaviour, the
      influence of the phase forming constituents was assessed towards the partition
      coefficients and recovery percentages of vanillin and l-ascorbic acid among the
      coexisting phases. Both model systems and real processed food waste materials
      were employed. Using these ATPS as partitioning systems it is possible to recover
      and separate vanillin, which migrates for the alcohol-rich phase, from l-ascorbic
      acid, which preferentially partitions for the salt-rich phase.

PMID- 22980830
TI  - Chemical composition and antibacterial activity of Indian seagrasses against
      urinary tract pathogens.
AB  - Seagrasses have a long history of being used for a variety of remedial purposes,
      such as the fever, skin diseases, muscle pains, wounds and stomach problems.
      Hence it is essential to study their bioactive metabolites and medicinal
      properties when considering their food applications. The chemical composition of
      six seagrasses were determined and evaluated for their potential to urinary tract
      infection bacteria (UTI). The chemical composition determined by GC-MS yielded 24
      compounds. For the first time 4H-Pyran-4-one-2,3-dihydro-3,5-dihydroxy-6-methyl-
      (6.68%), d-allose (3.67%) and 5-Caranol, trans,trans-(+)- (2.14%) were identified
      from Halodule pinifolia. d-Allose is a aldo-hexose (sugar) used as a potential
      inhibitor of glycosidases and low-calorie carbohydrate sweeteners. Among the six
      seagrasses tested, H. pinifolia and Cymodocea rotundata exhibited predominant
      growth inhibitory activity against all the UTI bacteria. This study shows the
      presence of various biological metabolites in tested seagrasses that can be used
      effectively in food and pharmacological industries.

PMID- 22980829
TI  - Kinetics of temperature increase during tomato processing modulate the
      bioaccessibility of lycopene.
AB  - The nutritional benefit of bioactive metabolites depends on their
      bioavailability, i.e. the proportion that leaves the food matrix, and crosses the
      enteral barrier to reach their cellular target. The present study focused on
      lycopene, the major and bioactive tomato carotenoid, the bioavailability of which
      is known to be enhanced in cooked products. To better understand how processing
      may facilitate lycopene release, we assessed whether hot-break (HB) or cold-break
      (CB) treatments influence the tomato lycopene bioaccessibility. HB and CB are
      used in the tomato industry to modulate texture of purees through endogenous cell
      wall lytic enzymes activity. HB and CB processes were mimicked through microwave
      heating, leading to a differentiated temperature rise in the product. The HB and
      CB models led to the expected differences, i.e. more viscous puree for HB with
      low methanol. The ability of the tomato matrix to release lycopene was measured
      as the extractability of lycopene to oil under standardized mixing conditions. We
      expected that CB treatment, by enhancing cell-wall degradation, would lead to
      enhanced lycopene bioaccessibility. The opposite was observed: oil contained
      three times less lycopene when mixed by CB (around 0.3 MUgml(-1); similar to
      results obtained with fresh purees) than when mixed by HB (around 0.9 MUgml(-1)),
      although HB caused more lycopene degradation. Kinetics studies indicated that the
      quick rise of temperature at the beginning of HB treatment was a key parameter.

PMID- 22980831
TI  - Effect of pretreatment on lipid oxidation and fishy odour development in protein
      hydrolysates from the muscle of Indian mackerel.
AB  - Impact of different pretreatments on chemical compositions of Indian mackerel
      mince was studied. Mince prepared using washing/membrane removal/alkaline
      solubilisation process (W-MR-Al) contained the lowest remaining myoglobin and
      haem iron content and also showed the lowest total lipid and phospholipid
      contents. When mince and W-MR-Al were hydrolysed using Alcalase for up to 120
      min, a higher degree of hydrolysis (DH) was found in W-MR-Al after 30 min of
      hydrolysis. Furthermore, hydrolysate from W-MR-Al had lower peroxide value (PV),
      thiobarbituric acid reactive substances (TBARS) and non-haem iron content
      throughout hydrolysis period (P<0.05). When hydrolysate powder produced from
      mince and W-MR-Al (0-0.3%w/v) were fortified in milk, the former resulted in the
      lower likeness score (P<0.05) at all levels used. The addition of the latter, for
      up to 0.2%, had no effect on likeness of all attributes, compared with milk
      without fortification (P>0.05). Therefore, the appropriate pretreatment of mince
      yielded hydrolysate with lower fishy odour.

PMID- 22980832
TI  - Quantification by solid phase micro extraction and stable isotope dilution assay
      of norisoprenoid compounds in red wines obtained from Piedmont rare varieties.
AB  - A method to identify and quantify megastigmane norisoprenoid compounds in wines
      was developed using headspace solid phase micro extraction (SPME) coupled with
      gas-chromatography/mass-spectrometry (GC-MS). Three different compounds were
      quantified by stable isotope dilution assay (SIDA): beta-damascenone, beta-ionone
      and alpha-ionone. Particular attention was paid to maximising the method's
      sensitivity while reducing the extraction time. To optimise the extraction
      conditions, a statistically designed experiment was performed using extraction
      time, extraction temperature and ethanol content as operating variables. Five
      different SPME fibres suitable for the analysis of volatile compounds were
      compared. This study confirmed that the PDMS/DVB coating performs best for the
      quantification of beta-damascenone and beta-ionone, and the crucial influence of
      ethanol content of the sample on extraction effectiveness. Finally, the optimised
      method was applied to the study of various wines derived from rare and
      autochthonous grape varieties of north-western Italy.

PMID- 22980833
TI  - Physicochemical characteristics and antioxidant activity of arginine-modified
      melanin from Lachnum YM-346.
AB  - Seven kinds of amino acids were used to modify the non-water-soluble
      extracellular melanin (LEM346) from Lachnum YM-346. It was found that arginine
      melanin (ALEM346) had the highest solubility, being 4.55% (gg(-1)) in 30 degrees
      C distilled water. Elemental analysis, infrared spectrum and mass spectrum
      analysis revealed that LEM346 molecule contained indole quinone structure, its
      molecular formula speculated to be C(18)H(8)O(6)N(2). Infrared spectrum analysis
      showed that ALEM346 had characteristic absorption peaks at 1672.346 and 1637.679
      cm(-1). Mass spectrum analysis indicated that ALEM346 contained three types of
      arginine-melanin molecules. When the ALEM346 concentration was 500 mgL(-1), its
      total antioxidant capacity was equivalent to alpha-tocopherol of 46.65 mmolL(-1),
      the DPPH() and O(2)(-) scavenging rates and the Fe(2+) chelating rate were
      89.05%, 93.81% and 80.18%, respectively, suggesting that the antioxidant activity
      of ALEM346 was stronger than that of LEM346.

PMID- 22980834
TI  - Application of the SPI (Saliva Precipitation Index) to the evaluation of red wine
      astringency.
AB  - The aim of this work was to evaluate the astringency of red wines by means of a
      SDS-PAGE based-method. The optimization of the in vitro assay, named SPI (Saliva
      Precipitation Index) that measured the reactivity of salivary proteins towards
      wine polyphenols, has been performed. Improvements included the choice of
      saliva:wine ratio, saliva typology (resting or stimulated saliva), and
      temperature of binding. The LOD (0.05 g/L of condensed tannin) and LOQ (0.1g/L of
      condensed tannin) for the binding reaction between salivary proteins and tannins
      added in white wine were also determined. Fifty-seven red wines were analysed by
      the optimised SPI, the Folin-Ciocalteu Index, the gelatine index, the content of
      total tannins and the sensory quantitative evaluation of astringency. A
      significant correlation between the SPI and the astringency of red wines was
      found (R(2)=0.969), thus indicating that this assay may be useful as estimator of
      astringency.

PMID- 22980835
TI  - Chemical composition and sensory profile of pomelo (Citrus grandis (L.) Osbeck)
      juice.
AB  - Two cultivars (Citrus grandis (L.) Osbeck PO 51 and PO 52) of Malaysian pomelo
      juices were studied by examining their physicochemical properties (i.e. pH, 
      degrees Brix and titratable acidity), volatile and non-volatile components
      (sugars and organic acids). Using solvent extraction and headspace solid-phase
      microextraction, 49 and 65 volatile compounds were identified by gas
      chromatography-mass spectrometer/flame ionisation detector, respectively.
      Compared to pink pomelo juice (cultivar PO 52), white pomelo juice (cultivar PO
      51) contained lower amount of total volatiles but higher terpenoids. Descriptive
      sensory evaluation indicated that white pomelo juice was milder in taste
      especially acidity. Furthermore, principal component analysis and partial least
      square regression revealed a strong correlation in pomelo juices between their
      chemical components and some flavour attributes (i.e. acidic, fresh, peely and
      sweet). Hence, this research enabled a deeper insight into the flavour of this
      unique citrus fruit.

PMID- 22980836
TI  - Development of an ionic liquid-based microwave-assisted method for simultaneous
      extraction and distillation for determination of proanthocyanidins and essential
      oil in Cortex cinnamomi.
AB  - Cortex cinnamomi is associated with many health benefits and is used in the food
      and pharmaceutical industries. In this study, an efficient ionic liquid-based
      microwave-assisted simultaneous extraction and distillation (ILMSED) technique
      was used to extract cassia oil and proanthocyanidins from Cortex cinnamomi; these
      were quantified by gas chromatography/mass spectrometry (GC-MS) and the vanillin
      HCl colorimetric method, respectively. 0.5M 1-butyl-3-methylimidazolium bromide
      ionic liquid was selected as solvent. The optimum parameters of dealing with 20.0
      g sample were 230 W microwave irradiation power, 15 min microwave extraction time
      and 10 liquid-solid ratio. The yields of essential oil and proanthocyanidins were
      1.24 +/- 0.04% and 4.58 +/- 0.21% under the optimum conditions. The composition
      of the essential oil was analysed by GC-MS. Using the ILMSED method, the energy
      consumption was reduced and the extraction yields were improved. The proposed
      method was validated using stability, repeatability, and recovery experiments.
      The results indicated that the developed ILMSED method provided a good
      alternative for the extraction of both the essential oil and proanthocyanidins
      from Cortex cinnamomi.

PMID- 22980837
TI  - Extraction of ochratoxin A in bread samples by the QuEChERS methodology.
AB  - A QuEChERS method for the extraction of ochratoxin A (OTA) from bread samples was
      evaluated. A factorial design (2(3)) was used to find the optimal QuEChERS
      parameters (extraction time, extraction solvent volume and sample mass). Extracts
      were analysed by LC with fluorescence detection. The optimal extraction
      conditions were: 5 g of sample, 15 mL of acetonitrile and 3 min of agitation. The
      extraction procedure was validated by systematic recovery experiments at three
      levels. The recoveries obtained ranged from 94.8% (at 1.0 MUg kg(-1)) to 96.6%
      (at 3.0 MUg kg(-1)). The limit of quantification of the method was 0.05 MUg kg(
      1). The optimised procedure was applied to 20 samples of different bread types
      ("Carcaca", "Broa de Milho", and "Broa de Avintes") highly consumed in Portugal.
      None of the samples exceeded the established European legal limit of 3 MUg kg(
      1).

PMID- 22980838
TI  - Characterisation of an acidic peroxidase from papaya (Carica papaya L. cv Tainung
      No. 2) latex and its application in the determination of micromolar hydrogen
      peroxide in milk.
AB  - An acidic peroxidase isoform, POD-A, with a molecular mass of 69.4 kDa and an
      isoelectric point of 3.5 was purified from papaya latex. Using o-phenylenediamine
      (OPD) as a hydrogen donor (citrate-phosphate as pH buffer), the optimum pH for
      the function of POD-A was 4.6, and the optimum temperature was 50 degrees C. The
      peroxidase activity of POD-A toward hydrogen donors was both pH- and
      concentration-dependent. Under optimal conditions, POD-A catalysed the oxidation
      of OPD at higher rates than pyrogallol, catechol, quercetin and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS). The chemical modification reagents
      N-bromosuccinimide and sodium azide significantly inhibited POD-A activity. The
      results of kinetic studies indicated that POD-A followed a ping-pong mechanism
      and had a K(m) value of 2.8mM for OPD. Using CPC silica-immobilised POD-A for the
      determination of micromolar H(2)O(2) in milk, the lower limit of determination
      was 0.1 MUM, and the recoveries of added H(2)O(2) were 96-109%.

PMID- 22980839
TI  - Separation, purification and quantification of verbascoside from Penstemon
      barbatus (Cav.) Roth.
AB  - Echinacoside and verbascoside possess a spectrum of significant beneficial
      bioactivities. A new method of preparative high-speed counter-current
      chromatography for rapid separation and purification of verbascoside from the
      leaves of Penstemon barbatus (Cav.) Roth was introduced. The solvent system
      employed here was n-butanol-water (1:1, v/v). The structure was confirmed by IR,
      (1)H NMR and (13)C NMR. According to the quantification results, echinacoside and
      verbascoside were found to be as much as 5.25 +/- 0.13 mg/g and 11.21 +/- 0.16
      mg/g, respectively, in the leaves of P. barbatus. This indicates that P. barbatus
      might be an ideal alternative resource for large scale preparation of
      echinacoside and verbascoside.

PMID- 22980840
TI  - A simple method for positional analysis of phosphatidylcholine.
AB  - Simple and fast method of positional analysis of fatty acid composition of
      phosphatidylcholine (PC) from egg-yolk and soy has been elaborated. The key step
      of the procedure was complete ethanolysis of PC catalyzed by sn-1,3 specific
      lipase from Mucor miehei (Lipozyme). 2-Acyl-lysophosphatidylcholine (2-acyl LPC),
      fatty acids ethyl esters (FAEEs) and free fatty acids (FAs) were formed in this
      process. No acyl migration was observed during the reaction. The products were
      entirely separated from the products mixture by simple extraction in water:hexane
      (2:3 v/v) system. The hexane fraction containing free FAs and FAEEs was treated
      with BF(3)/Et(2)O in ethanol to obtain only FAEEs. The analysis of FAEEs by GC
      gave the composition of the FAs in the sn-1 position of the PC. 2-Acyl LPC from
      water fraction after precipitation in cold (-20 degrees C) acetone was converted
      into FAEEs and analyzed by gas chromatography (GC) to determine FAs composition
      in the sn-2 position of the PC.

PMID- 22980841
TI  - Assay of picogram level isocarbophos residue on tangerines and oranges with
      luminol-albumin chemiluminescence system.
AB  - A sensitive flow injection-chemiluminescence (FI-CL) method for the determination
      of isocarbophos (ICP) residue on tangerines and oranges was proposed. It was
      found that the CL intensity from luminol-albumin CL reaction could be obviously
      quenched in the presence of ICP and the decrease in CL intensity was proportional
      to the logarithm of ICP concentrations ranging from 1.0 to 1000 pmol L(-1),
      giving the limit of detection of 0.3 pmol L(-1) (3sigma). The proposed procedure
      was successfully applied to the determination of ICP residue on tangerines and
      oranges with recoveries varying from 92.0 to 111.0% and RSDs less than 5.0%. The
      possible CL mechanism of luminol-albumin-ICP reaction was discussed, and ICP to
      albumin's binding constant (K(D)=1.00 * 10(6) L mol(-1)) and the number of
      binding sites (n=1.00) were given by the homemade FI-CL model.

PMID- 22980842
TI  - Characterisation and authentication of A. senegal and A. seyal exudates by
      infrared spectroscopy and chemometrics.
AB  - The authentication of Acacia gums samples requires usually the use of
      sophisticated and time consuming analytical techniques. There is a need for fast
      and simple analytical techniques for the objective of a quality control
      methodology. Commercial Acacia senegal and Acacia seyal gums present
      characteristic MIR spectra. Principal Component Analysis of the infrared spectra
      of gum exudates of trees allow to distinguish Acacia gums from another gum
      exudates (Combretum, Ghatti, Karaya, Tragacanth). Moreover, gums of A. senegal
      and A. seyal separate them and from other Acacia species (Acacia dealbata, Acacia
      karoo, Acacia nilotica, Acacia sieberiana). Chemometric treatments of A. senegal
      and A. seyal MIR spectra were assessed for the quantification of moisture content
      in Acacia gums, for the classification into the two species and for the
      adulteration detection and quantification. Results were quite satisfactory, the
      moisture content was estimated at 3.1%, adulteration was detected at 3.4% and
      quantified at 5.6%. The discrimination of the two species is done without any
      ambiguity.

PMID- 22980843
TI  - Influence of harvest year, cultivar and geographical origin on Greek extra virgin
      olive oils composition: a study by NMR spectroscopy and biometric analysis.
AB  - Two hundred twenty-one extra virgin olive oils (EVOO) were extracted from four
      olive mono-cultivars (Koroneiki, Tsounati, Adramitini, and Throubolia) originated
      from four divisions of Greece (Peloponnesus, Crete, Zakynthos, and Lesvos) and
      collected in five harvesting periods (2002-2006 and 2007-2008). All samples were
      chemically analysed by means of (1)H and (31)P NMR spectroscopy and characterised
      according to their content in fatty acids, phenolic compounds, diacylglycerols,
      total free sterols, free acidity, and iodine number. The influence of cultivars
      on the compositional data of the EVOO samples according to harvest year and
      geographical origin was examined by means of the forward stepwise canonical
      discriminant analysis (CDA) and classification binary trees (CBT). The CDA, when
      the a priori grouping was in accordance with harvest, was high (94%), whereas the
      classification in terms of groups formed by inclusions of geographical origin was
      reduced to 85%. Inclusion of both the harvesting year and geographical origin in
      the CDA analysis resulted in a high classification (90%) for the EVOO samples
      grouped into the four cultivars. The variables that most satisfactorily
      classified the Greek olive oils were the phenolics p-coumaric acid, pinoresinol,
      1-acetoxypinoresinol, syringaresinol, luteolin, apigenin, and the hydrolysis
      products of oleuropein expressed collectively by the concentration of total
      hydroxytyrosol. Amongst the fatty acids, linoleic acid was the predictor with the
      highest discriminatory power. Finally, the phylogenetic significance of the olive
      oil compounds as determined by NMR was investigated by estimating their support
      to monophyly of cultivars.

PMID- 22980844
TI  - Effect of lipid oxidation products on the formation of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) in model systems.
AB  - Ternary mixtures of creatinine, phenylalanine and lipids (or carbohydrates) were
      heated at 200 degrees C for 1h to determine the potential contribution of lipids
      to the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
      Although unoxidised lipids did not contribute to PhIP formation, their oxidation
      produced many compounds that significantly increased the formation of PhIP. Among
      the different lipid oxidation products (LOPs) studied, which included omega-6 and
      omega-3 derived lipid hydroperoxides, 2,4-alkadienals, 2-alkenals, 4,5-epoxy-2
      alkenals, 4-oxo-2-alkenals, and 4-hydroxy-2-nonenal, 4-oxo-2-nonenal was the most
      reactive compound. It produced 32.48 pmol of PhIP/MUmol of creatinine in
      comparison with the 7.92 pmol of PhIP/MUmol of creatinine produced by the control
      phenylalanine/creatinine reaction mixture. 4-Oxo-2-nonenal reactivity was similar
      to that of most carbohydrates; although ribose and arabinose produced more PhIP
      (44-46 pmol of PhIP/MUmol of creatinine). In addition to single LOP, the addition
      of oxidised soybean oil for 24-144 h at 60 degrees C also increased PhIP
      formation. All these results pointed out to a potential contribution of LOP to
      the formation of PhIP in food products. This contribution will depend on the
      lipid content of the food product and its easiness to be oxidised.

PMID- 22980845
TI  - Climatic factors directly impact the volatile organic compound fingerprint in
      green Arabica coffee bean as well as coffee beverage quality.
AB  - Coffee grown at high elevations fetches a better price than that grown in lowland
      regions. This study was aimed at determining whether climatic conditions during
      bean development affected sensory perception of the coffee beverage and
      combinations of volatile compounds in green coffee. Green coffee samples from 16
      plots representative of the broad range of climatic variations in Reunion Island
      were compared by sensory analysis. Volatiles were extracted by solid phase micro
      extraction and the volatile compounds were analysed by GC-MS. The results
      revealed that, among the climatic factors, the mean air temperature during seed
      development greatly influenced the sensory profile. Positive quality attributes
      such as acidity, fruity character and flavour quality were correlated and typical
      of coffees produced at cool climates. Two volatile compounds (ethanal and
      acetone) were identified as indicators of these cool temperatures. Among detected
      volatiles, most of the alcohols, aldehydes, hydrocarbons and ketones appeared to
      be positively linked to elevated temperatures and high solar radiation, while the
      sensory profiles displayed major defects (i.e. green, earthy flavour). Two
      alcohols (butan-1,3-diol and butan-2,3-diol) were closely correlated with a
      reduction in aromatic quality, acidity and an increase in earthy and green
      flavours. We assumed that high temperatures induce accumulation of these
      compounds in green coffee, and would be detected as off-flavours, even after
      roasting. Climate change, which generally involves a substantial increase in
      average temperatures in mountainous tropical regions, could be expected to have a
      negative impact on coffee quality.

PMID- 22980846
TI  - Iron reduction potentiates hydroxyl radical formation only in flavonols.
AB  - Flavonoids, substantial components of the human diet, are generally considered to
      be beneficial. However, they may possess possible pro-oxidative effects, which
      could be based on their reducing potential. The aims of this study were to
      evaluate the ability of 26 flavonoids to reduce ferric ions at relevant pH
      conditions and to find a possible relationship with potentiation of hydroxyl
      radical production. A substantial ferric ions reduction was achieved under acidic
      conditions, particularly by flavonols and flavanols with the catecholic ring B.
      Apparently corresponding bell-shaped curves displaying the pro-oxidant effect of
      flavonols quercetin and kaempferol on iron-based Fenton reaction were documented.
      Several flavonoids were efficient antioxidants at very low concentrations but
      rather inefficient or pro-oxidative at higher concentrations. Flavonols, morin
      and rutin were progressively pro-oxidant, while 7-hydroxyflavone and hesperetin
      were the only flavonoids with dose-dependent inhibition of hydroxyl radical
      production. Conclusively, administration of flavonoids may lead to unpredictable
      consequences with few exceptions.

PMID- 22980847
TI  - Quantitative and qualitative variability of the caseinolytic potential of
      different strains of Pseudomonas fluorescens: implications for the stability of
      casein micelles of UHT milks during their storage.
AB  - Pseudomonas fluorescens grows at low temperature and produces thermo-resistant
      protease(s) that can destabilize UHT (Ultra High Temperature) milk during its
      storage. The consequences of contamination of microfiltered milk with 9 strains
      of P. fluorescens on the stability of the corresponding UHT milk during storage
      had been investigated in this study. The strains were classified in two groups
      according to their ability to destabilize UHT milk. For the group of highly
      destabilizing strains, sedimentations of UHT milks, low values to phosphate test
      and the presence of aggregates were observed. Zeta potential and hydration of
      casein micelles decreased, whereas non casein nitrogen (NCN) and non protein
      nitrogen (NPN) contents increased. The analyses of NCN fraction by liquid
      chromatography coupled to mass spectrometry indicated that the different casein
      molecules were hydrolyzed in a similar way for the destabilizing strains
      suggesting that the same enzyme was implicated. For the group of slightly or not
      destabilizing strains no visual and biochemical alteration were found. This study
      showed that destabilization of UHT milk by P. fluorescens was highly variable and
      strain-dependent.

PMID- 22980848
TI  - Concentrations of biogenic amines in fish, squid and octopus and their changes
      during storage.
AB  - The concentrations of seven biogenic amines (BA) were simultaneously determined
      in 74 samples of fish, squid and octopus, by the method of HPLC coupled with pre
      column derivatisation. The relationship between the formation of BA in aquatic
      products and the growth of microbial flora during storage was also investigated.
      Results showed that putrescine, cadaverine, histamine and tyramine were the
      dominant BA in the studied samples, but the concentrations of histamine and
      tyramine were mostly less than 50 and 100 mgkg(-1), respectively. Freezing can
      effectively prevent the formation of BA, but the levels of putrescine,
      cadaverine, histamine and tyramine significantly increased (p<0.05) during
      storage at 4 and 25 degrees C. The growth of mesophilic or psychrophilic bacteria
      in blue scad and octopus strongly and positively correlated with the formation of
      amines (such as putrescine, cadaverine, histamine and tyramine) during storage,
      except for histamine in octopus.

PMID- 22980849
TI  - Multi residue determination of the penicillins regulated by the European Union,
      in bovine, porcine and chicken muscle, by LC-MS/MS.
AB  - A multiresidue analysis method was developed to determine the content of
      penicillins in bovine, porcine and chicken muscle tissues. The procedure involves
      solid phase extraction (SPE) and subsequent analysis by liquid chromatography
      coupled with tandem mass spectrometry detection (LC-MS/MS) set by the European
      Union (EU) for all compounds. The method was validated according to EU guideline
      2002/657/EC. The LOQ in tissues are below the maximum residue limits (MRLs) and
      appropriate quality parameters in terms of linearity, accuracy (recoveries higher
      than 70% for all antibiotics and animal tissues except for AMOX with 50% of
      recovery) and precision (in terms of intra and inter day with values lower than
      12% in all cases) are obtained for the developed method. A study concerning to
      the matrix effect was made and it was concluded that similar matrix effect could
      be found in beef, pig and chicken. The method was applied to the analysis of
      samples of chicken from animals treated with amoxicillin.

PMID- 22980850
TI  - Study on iron availability from prepared soybean sprouts using an iron-deficient
      rat model.
AB  - During soya seeds germination in FeSO(4) solutions their phytoferritin content is
      multiplied. Prepared soybean sprouts have been proposed as a safe and easily
      available source of iron supplementation. The preparation was compared with
      FeSO(4) and ferritin isolates, using rats with induced iron deficiency anaemia.
      After the end of the 2-week supplementation experiment, it was observed that no
      statistically significant differences in haemoglobin concentration, mean
      corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular
      haemoglobin concentration existed between those animals supplemented with sprouts
      enriched in ferritin, ferritin isolate and FeSO(4) and healthy animals forming
      the control group. Moreover, the examined preparation had a beneficial influence
      on the recreation of ferritin reserves in both the liver and the blood serum, and
      also did not induce negative alterations in general growth parameters of animals.
      Use of an easily obtainable ferritin iron source may be a profitable alternative
      in supplementation due to its wide availability and food preservative properties.

PMID- 22980851
TI  - Volatile organic compounds from a Tuber melanosporum fermentation system.
AB  - A total of 59 volatile organic compounds (VOCs) were identified from Tuber
      melanosporum fermentation: 53 from its fermented mycelia and 32 from the
      fermentation broth. Alcohol-derived compounds were predominant in both the
      fermentation mycelia and the broth, although long chain fatty acids and
      isoprenoids were, for the first time, also found in the mycelia. The intense wine
      bouquet properties of the broth arose from several specific flavor substances,
      including sulfur compounds, pyrazines, furans and jasmones. Comparing the VOCs
      identified in this work with those previously reported, our results are more
      similar to the composition of the Tuber fruiting-body than previous Tuber
      fermentations. The composition and accumulation of flavor volatiles (e.g.,
      pyrazines, sulfur compounds, and esters) and major constituents (e.g., 3-methyl-1
      butanol and 2-phenylethanol) in this fermentation were significantly influenced
      by the sucrose concentration in the medium. The obtained information could
      therefore be useful in applications to convert the flavors of truffle mycelia
      similar to those of the fruiting-body by optimising the fermentation process.

PMID- 22980853
TI  - Expression of alpha-amylase inhibitors in diploid Triticum species.
AB  - The aim of the work was to characterize the expression of various alpha-amylase
      inhibitors (alphaAIs), well known anti-nutritional compounds, for the development
      of healthier diploid wheat-based functional foods. The salt-soluble protein
      fractions from the seeds of 53 accessions among Triticum monococcum subsp.
      monococcum (T.m.), T. monococcum subsp. boeoticum (T.b.) and Triticum urartu
      (T.u.) were analyzed by immunoblotting after SDS-PAGE and Urea-PAGE using
      polyclonal antibodies (PABs) raised against 0.19 and 0.28 alphaAIs expressed in
      bread-wheat. Reverse zymography with human saliva and Tenebrio molitor alpha
      amylases was used to assay inhibition activity. A great variability of the
      expression of alphaAI-related proteins was observed among T.b. and T.u. PABs, and
      reverse zymography revealed different bands, often not correlating with those
      present in bread-wheat. Two-dimensional electrophoresis followed by
      immunoblotting and mass spectrometric analysis identified these proteins as
      alphaAIs. Interestingly, no signal was observed within T.m. accessions. This
      makes T.m. an important candidate for the production of novel functional foods.

PMID- 22980852
TI  - Discovering Bisdemethoxycurcumin from Curcuma longa rhizome as a potent small
      molecule inhibitor of human pancreatic alpha-amylase, a target for type-2
      diabetes.
AB  - Curcuma longa rhizome is used extensively in culinary preparations in Far East
      and South-East Asia. Health benefits of curcuminoids from C. longa as
      antioxidants, anti-cancer and anti-inflammatory molecules have been well
      documented. We report here for the first time that Bisdemethoxycurcumin (BDMC)
      from C. longa, acts as an inhibitor to inactivate human pancreatic alpha-amylase,
      a therapeutic target for oral hypoglycemic agents in type-2 diabetes. Bioactivity
      guided isolation of rhizome isopropanol extract led to the identification by HPLC
      and NMR of BDMC as a lead small molecule inhibitor of porcine and human
      pancreatic alpha-amylase with an IC(50) value of 0.026 and 0.025 mM,
      respectively. Kinetic analysis revealed that using starch as the substrate, HPA
      exhibited an uncompetitive mode of inhibition with an apparent K(i) of 3.0 MUM.
      The study gains importance as BDMC could be a good drug candidate in development
      of new inhibitors of HPA and of functional foods for controlling starch digestion
      in order to reduce post-prandial hyperglycemia.

PMID- 22980854
TI  - Prediction of the amount and rate of histamine degradation by diamine oxidase
      (DAO).
AB  - Histamine is a biogenic amine that forms in a variety of foods and can cause food
      poisoning at high concentrations (>500 ppm). In situations where the formation of
      histamine in food cannot be prevented through refrigeration, diamine oxidase
      (DAO) enzyme may be used to degrade histamine to safe levels. The aims of this
      work were to apply DAO in model (buffer) and real (cooked tuna soup used in the
      manufacture of a fish paste product, Rihaakuru) systems, in order to obtain
      predictions for the rates and amounts of histamine degradation. The two systems
      were set up with a constant concentration of histamine (500 mg/L) and the DAO
      enzyme (2534 units/L) at a temperature of 37 degrees C, agitation at 100 rpm and
      an incubation time of 10h with variable pH (5-7) and salt concentrations (1-5%).
      A total of 15 experiments were designed for each system using central composite
      design (CCD). The data from these experiments were fitted into regression models;
      initially the data were used to generate an exponential decline model and then
      the data from this were fitted into a secondary response surface model (RSM) to
      predict the rate and amount of histamine degradation by DAO. The model system
      results indicated that DAO activity was not significantly affected by salt
      (p>0.05), and that activity reached a maximum within the pH range of 6-6.5 with
      an optimum at pH 6.3. However, the results obtained with the tuna soup model
      showed that the optimum oxidation of histamine using DAO occurred between pH 6-7
      and salt 1-3%. This study defined the conditions for the use of DAO to degrade
      500 mg/L of histamine in tuna soup used to manufacture Rihaakuru. The models
      generated could also be used to predict the rate and amount of histamine
      degradation in other foods that have similar characteristics to tuna soup.

PMID- 22980855
TI  - Development of a monoclonal antibody-based sandwich-type enzyme-linked
      immunosorbent assay (ELISA) for detection of abrin in food samples.
AB  - Abrin is a plant toxin, which can be easily isolated from the seeds of Abrus
      precatorius. It may be used as a biological warfare agent. In order to detect
      abrin in food samples, a two-layer sandwich format enzyme-linked immunosorbent
      assay based on the monoclonal antibody (mAb) (as capture antibody) and rabbit
      polyclonal serum (as detecting antibody) was developed and applied for the
      determination of abrin in some food matrices. The linear range of the mAb was 1
      100 MUg L(-1) with a detection limit of 0.5 MUg L(-1) for abrin in phosphate
      buffered saline (PBS). The recoveries of abrin from sausage, beer and milk
      samples ranged 97.5-98.6%, 95.8-98.4% and 94.8-9.6%, respectively, with a
      coefficient of variation (CV) of 3.7% or less. The newly developed sandwich ELISA
      using the mAb appears to be a reliable and useful method for detection of abrin
      in sausage, beer and milk.

PMID- 22980856
TI  - Determining the geographical origin of Chinese cabbages using multielement
      composition and strontium isotope ratio analyses.
AB  - Recently, the Korean market has seen many cases of Chinese cabbage (Brassica rapa
      ssp. pekinensis) that have been imported from China, yet are sold as a Korean
      product to illegally benefit from the price difference between the two products.
      This study aims to establish a method of distinguishing the geographical origin
      of Chinese cabbage. One hundred Chinese cabbage heads from Korea and 60 cabbage
      heads from China were subjected to multielement composition and strontium isotope
      ratio ((87)Sr/(86)Sr) analyses. The (87)Sr/(86)Sr ratio differed, based on the
      geological characteristics of their district of production. In addition, the
      content of many elements differed between cabbages from Korea and China. In
      particular, the difference in the content of Sr and Ti alone and the combination
      of Sr, Ca, and Mg allowed us to distinguish relatively well between Korea and
      China as the country of origin. The present study demonstrates that the chemical
      and Sr isotopic analyses exactly reflect the geology of the production areas of
      Chinese cabbage.

PMID- 22980857
TI  - ICP-AES determination of minor- and major elements in apples after microwave
      assisted digestion.
AB  - The aim of this paper was to determine the content of minor and major elements in
      apples by inductively coupled plasma atomic emission spectrometry (ICP-AES).
      Prior to ICP-AES measurement, dried apples were digested in a microwave assisted
      digestion system. The differences in the measured element concentrations after
      application of open and closed microwave system as sample preparation procedures
      are discussed. In whole apples, flesh and peel Ag, Al, Ba, Ca, Cd, Co, Cr, Cu,
      Fe, K, Mg, Mn, Na, Ni, Pb, Sr and Zn were analysed after optimisation and
      validating the analytical method using ICP-AES. The accuracy of the method
      determined by spiking experiments was very good (recoveries 88-115%) and the
      limits of detection of elements of interest were from 0.01 up to 14.7 MUg g(-1).
      The reference ranges determined in all apple samples are 39-47 mg g(-1) for K, 9
      14 mg g(-1) for Na, 3-7 mg g(-1) for Mg, 3-7 MUg g(-1) for Zn, 0.7-2.8 MUg g(-1)
      for Sr. The range of Mn in peel 4-6 MUg g(-1) is higher compared to whole apple
      from 0.7 to 1.7 MUg g(-1). Cd is found only in peel, in the concentration range
      of 0.4-1.1 MUg g(-1).

PMID- 22980858
TI  - Monoclonal antibody based inhibition ELISA as a new tool for the analysis of
      melamine in milk and pet food samples.
AB  - Stories of recent cases about melamine misuse to raise the false impression of a
      high protein content of milk in China emerged in September of 2008, have become
      an international health event. To meet the need for rapid and reliable monitoring
      of melamine in milk samples, a monoclonal antibody (mAb) was produced and an
      inhibition enzyme-linked immunosorbent assay (ELISA) was developed based on the
      mAb. The standard curve was linear in the range from 0.03 to 9 ng mL(-1) with a
      detection limit (LOD) of 0.01 ng mL(-1). The sensitivity of the assay was 0.35 ng
      mL(-1). The average recovery values of melamine in the liquid milk, powder milk,
      dog food and cat food were 99%, 96%, 9% and 98%, respectively and the coefficient
      of variation (CV) values of all samples were less than 10%. The obtained results
      showed a potential method as a tool for the rapid and reliable monitoring of
      melamine in liquid milk and milk powder samples (158 words).

PMID- 22980859
TI  - Rapid mixed mode solid phase extraction method for the determination of
      acrylamide in roasted coffee by HPLC-MS/MS.
AB  - In this work, a rapid and reliable purification method based on a single mixed
      solid phase extraction (SPE) column, for the determination of acrylamide in
      roasted coffee by liquid chromatography-tandem mass spectrometry, was developed.
      Deuterium labelled d(3)-acrylamide was used as internal standard. Acrylamide was
      extracted by 10 mL of water and the extract purified by a single SPE column
      consisting of 0.5 g of an in-house prepared mixture of C18, strong cation (SCX)
      and anion exchange (SAX) sorbents in the ratio 2/1.5/1.5 (w/w/w). The amount of
      the three sorbents was optimised in order to eliminate the main interfering
      compounds present in coffee extracts, such as melanoidins, trigonelline,
      chlorogenic acids and caffeine. The SPE procedure was very simple and consisted
      of pushing 1 mL of an aqueous coffee extract through the SPE column followed by 1
      mL of water which was collected for the analysis. The method was tested on six
      samples of roasted coffee of different composition and roasting level. The
      repeatability of the method, expressed as relative standard deviation (n=6), was
      lower than 5%. The recovery of acrylamide at three spiked levels ranged from 92%
      to 95%. The limits of detection (LOD) and quantitation (LOQ) were 5 and 16 MUg
      kg(-1), respectively.

PMID- 22980860
TI  - Effects of different vinification technologies on physical and chemical
      characteristics of Sauvignon blanc wines.
AB  - In order to investigate the effects of cryomaceration and reductive vinification
      on chemical and physical indices and on antioxidant compounds of Sauvignon blanc
      wines, four wine-making procedures were applied: traditional white vinification,
      skin cryomaceration, vinification in a reductive environment, and a combination
      of the last two procedures. Significant differences were highlighted by both
      conventional analyses and NMR spectroscopy. The strongest changes were for
      organic acid concentrations (tartaric, in particular) and phenolic content.
      Cryomaceration caused a strong precipitation of tartaric acid, which may be
      desired if grapes have high acidity values. Cryomaceration protected those
      flavans reactive with vanillin from the action of oxidative enzymes. Vinification
      in a reductive environment, alone or combined with a cryomaceration step, gave
      wines with the highest solids content and caused a greater extraction of phenolic
      compounds from skins compared to traditional winemaking or cryomaceration alone,
      due to SO(2) solubilisation. Grape oenological expression can be strongly
      affected by the application of the investigated wine-making procedures.

PMID- 22980861
TI  - In vivo investigation on the potential of galangin, kaempferol and myricetin for
      protection of D-galactose-induced cognitive impairment.
AB  - The potential of three natural flavonols (galangin, kaempferol and myricetin) to
      protect against D-galactose-induced cognitive impairment in mice was
      investigated. After 8 weeks treatment, the mice were assessed by behavioural
      tests. The levels of oxidative stress, the amount of Na(+),K(+)-ATPase and
      extracellular signal-regulated kinases (ERK)-cyclic AMP response element binding
      protein (CREB) signaling pathway in hippocampus were also analysed. It was found
      that all the three dietary flavonols could ameliorate the oxidative stress,
      enhance the activity of Na(+),K(+)-ATPase and regulate the expression of ERK-CREB
      pathway in mice. However, only kaempferol and myricetin could significantly
      improve the learning and memory capability when compared with D-galactose model.
      Our results suggest that the presence of hydroxyl groups in the B ring of
      flavonols may have contribution to the neuroprotective activity.

PMID- 22980862
TI  - Taiwanofungus camphorata nitroreductase: cDNA cloning and biochemical
      characterisation.
AB  - Nitroreductases (Nrs) play important roles in redox system via NADPH or NADH as a
      reductant. A TcNr cDNA encoding a putative Nr was cloned from Taiwanofungus
      camphorata. A 3-D structural model of the TcNr has been created based on the
      known structure of BcNr (Bacillus cereus). To characterise the TcNr, the coding
      region was subcloned into an expression vector and transformed into Escherichia
      coli. The recombinant His(6)-tagged TcNr was purified by Ni affinity
      chromatography. The purified enzyme showed a single band at molecular mass of
      approximately 25 kDa on 12% sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis. The enzyme exhibited Nr activity via ferricyanide assay. The
      Michaelis constant (K(M)) value for ferricyanide was 0.86 mM. The enzyme(')s half
      life of deactivation at 45 degrees C was 12.3 min. The enzyme was most active at
      pH 6. The enzyme's preferred substrate is 1-chloro-2, 4-dinitrobenzene.

PMID- 22980863
TI  - Optimisation of flavour ester biosynthesis in an aqueous system of coconut cream
      and fusel oil catalysed by lipase.
AB  - Coconut cream and fusel oil, two low-cost natural substances, were used as
      starting materials for the biosynthesis of flavour-active octanoic acid esters
      (ethyl-, butyl-, isobutyl- and (iso)amyl octanoate) using lipase Palatase as the
      biocatalyst. The Taguchi design method was used for the first time to optimize
      the biosynthesis of esters by a lipase in an aqueous system of coconut cream and
      fusel oil. Temperature, time and enzyme amount were found to be statistically
      significant factors and the optimal conditions were determined to be as follows:
      temperature 30 degrees C, fusel oil concentration 9% (v/w), reaction time 24h, pH
      6.2 and enzyme amount 0.26 g. Under the optimised conditions, a yield of
      14.25mg/g (based on cream weight) and signal-to-noise (S/N) ratio of 23.07 dB
      were obtained. The results indicate that the Taguchi design method was an
      efficient and systematic approach to the optimisation of lipase-catalysed
      biological processes.

PMID- 22980864
TI  - Impact of zinc salts on heat-induced aggregation of natural actomyosin from
      yellow stripe trevally.
AB  - Impact of zinc sulphate (ZnSO(4)) and zinc chloride (ZnCl(2)) on heat-induced
      aggregation of natural actomyosin (NAM) extracted from yellow stripe trevally
      (Selaroides leptolepis) was investigated. In the presence of ZnSO(4) or ZnCl(2),
      the transition temperature (T(max)) of myosin shifted from 47.83 +/- 0.30 degrees
      C to 46.05 +/- 0.36 and 46.49 +/- 0.49 degrees C, with the coincidental decreases
      in DeltaH from 1.07 +/- 0.03 J/g to 0.63 +/- 0.02 and 0.67 +/- 0.04 J/g,
      respectively (P<0.05). Additionally, Ca(2+)-ATPase activity of NAM decreased with
      increasing the concentrations of ZnSO(4) or ZnCl(2) during heating up to 40
      degrees C. During heating from 20 to 75 degrees C, higher turbidity, surface
      hydrophobicity and disulphide bond formation were obtained in NAM added with
      ZnSO(4) or ZnCl(2) at temperatures ranging from 40 to 75 degrees C, compared with
      the control. Nevertheless, a higher aggregation was found in NAM added with
      ZnSO(4,) compared with ZnCl(2.) Zeta potential (zeta) analysis suggested that the
      surface of NAM added with ZnSO(4) became less negatively charged, compared with
      that of ZnCl(2) counterpart. Transmission electron microscopy showed that the
      structure of NAM was highly interconnected, finer and denser when zinc salts,
      especially ZnSO(4) were incorporated. Therefore, ZnSO(4) could be used to induce
      aggregation of fish muscle proteins, thereby improving gelling property of fish
      mince or surimi.

PMID- 22980865
TI  - Induction of the cell cycle arrest and apoptosis by flavonoids isolated from
      Korean Citrus aurantium L. in non-small-cell lung cancer cells.
AB  - This study investigated the anti-proliferative and apoptotic effect of flavonoids
      isolated from Korean Citrus aurantium L. using A549 lung cancer cells. Flavonoids
      potently inhibited of A549 cells in a dose-dependent manner, whereas flavonoids
      had a weak inhibitory effect on proliferation of WI-38 cells. Flow cytometry and
      Western blot analysis showed that flavonoids induced cell cycle arrest at the
      G2/M checkpoint by controlling the proteins expression level of cyclin B1, cdc2,
      cdc25c and p21(WAF1/CIP1). Also, flavonoids induced apoptosis through the
      regulation of the expression of caspases, cleaved PARP and Bax/Bcl-xL ratio. The
      activity of caspase-3 on A549 cells increased in a dose-dependent manner. These
      results clearly indicated that the anti-cancer effect of flavonoids on A549 cells
      follows multiple cellular pathways through G2/M arrest and the induction of
      apoptosis.

PMID- 22980866
TI  - Influence of chromoplast morphology on carotenoid bioaccessibility of carrot,
      mango, papaya, and tomato.
AB  - Based on the observation of outstanding dissimilarities of the morphology of
      pigment-containing chromoplasts in nutritionally important carotenoid sources,
      the bioaccessibility (BA) of carotenoids from edible portions of carrot, mango,
      papaya, and tomato was compared using an in vitro digestion model. While carrot
      and tomato contained large carotenoid crystals clearly visible by light
      microscopy, mango and papaya contained different types of carotenoid-bearing
      structures. Particularly, beta-carotene is deposited in globular and tubular
      elements in papaya and mango chromoplasts, where carotenoids accumulate in a
      lipid-dissolved and liquid-crystalline form, respectively. The highest BA of beta
      carotene was found for mango (10.1%), followed by papaya (5.3%), tomato (3.1%),
      and carrot (0.5%). In our digestion model, differences between total lycopene BA
      from papaya and tomato were insignificant, possibly since both pigments occur in
      a solid crystalline deposition form in both fruits. Furthermore, the BA of
      lutein, beta-cryptoxanthin, and beta-cryptoxanthin esters was shown to be
      superior to that of the carotenes from the respective food sources. The effect of
      lipid addition to the different food sources was studied. Although BA was
      enhanced for most carotenoids, the above-mentioned ranking of BAs of beta
      carotene remained unchanged after lipid addition. Consequently, the physical form
      of carotenoid deposition in plant chromoplasts is suggested to have major impact
      on their liberation efficiency from the food matrices.

PMID- 22980867
TI  - Simultaneous determination of riboflavin and pyridoxine by UHPLC/LC-MS in UK
      commercial infant meal food products.
AB  - An assay for the simultaneous quantitative determination of riboflavin and
      pyridoxine in eight different complementary infant meal products has been
      developed in order to (1) estimate the daily intake of these vitamins from
      commercial infant food consumption, and (2) ascertain their nutritional
      suitability relative to dietary guidelines for the 6-9 months age group. The
      method involves mild hydrolysis of the foods, an extraction of the supernatant by
      centrifugation followed by quantitative determination using ultra-high
      performance liquid chromatography. Separation of the two water soluble vitamins
      is achieved within one minute and the resultant sample is also LC-MS compatible.
      Despite wide individual differences between brands (p=6.5e-12), no significant
      differences were observed in the level of pyridoxine between the meat and
      vegetable-based varieties (p=0.7) per 100g of commercial infant food. Riboflavin
      was not detected in any of the samples where the detection limit was below 0.07
      MUg/mL. In terms of the Reference Nutrient Intake (RNI) of pyridoxine for 6-9
      months old infants, the complementary infant meal products analysed herein
      provided less than 15% of the RNI values with mean (SD) values of 12.87 (+/-
      4.46)% and 13.88 (+/- 4.97)% for the meat- and vegetable-based recipes,
      respectively. The estimated total daily intake of riboflavin and pyridoxine from
      the consumption of commercial complementary food was found to be satisfactory and
      in accordance with the Dietary Reference Values (DRVs). The intake of both
      riboflavin and pyridoxine was estimated to be mainly derived from the consumption
      of formula milk which could be a cause of concern if the quality of an infant's
      milk diet is compromised by an inadequate or lack of supplemented milk intake.
      The results of this study suggest that the selected commercial complementary
      infant foods in the UK market may not contain the minimum levels of riboflavin
      and pyridoxine required for the labelling declaration of the micronutrient
      content of such products as recommended by Commission Directive 2006/125/EC.

PMID- 22980868
TI  - Levels of biogenic amines in retail market fermented meat products.
AB  - The qualitative and quantitative profile of biogenic amines (BA) in 50 samples of
      dry fermented sausages sold in Greek retail markets were determined by HPLC.
      Putrescine, cadaverine, tryptamine, beta-phenylethylamine spermidine, spermine
      were analysed by UV detection after pre-column derivatization with benzoyl
      chloride, whereas tyramine and histamine were analysed by fluorescence detection
      after post-column derivatization with o-phthaldialdehyde (OPA). With the
      exception of spermidine and spermine a wide variation of BA levels was observed
      among the samples. Of the BA examined, tyramine, putrescine, histamine and
      cadaverine showed high concentrations ranging from: 0 to 510 mg/kg (median: 197.7
      mg/kg), 0 to 505 mg/kg (median: 96.5mg/kg), 0 to 515 mg/kg (median: 7.0mg/kg) and
      0 to 690 mg/kg (median: 3.6 mg/kg), respectively. The histamine content of 28% of
      the samples exceeded the toxicity limit of 100mg/kg set for histamine in some
      fish species. Levels of tryptamine and beta-phenyl-ethylamine never exceeded 50
      and 29 mg/kg, respectively. Results of the present study suggest that the amounts
      of BA in dry fermented sausages, sold in Greek retail markets, may pose a
      potential health risk for sensitive individuals or for those undergoing classical
      monoamine oxidase inhibiting (MAOI) drug therapy.

PMID- 22980869
TI  - Low-cost visible-near infrared sensor for on-line monitoring of fat and fatty
      acids content during the manufacturing process of the milk.
AB  - This paper describes the calibration, validation and testing process of a low
      cost on-line visible-near infrared (400-1100 nm) sensor for the monitoring of fat
      and fatty acids content in milk during the manufacturing process of milk. The
      optical, mechanical and electronic designs of the sensor have been developed in
      Tekniker IK4 research centre just as its manufacturing process. The measurement
      range of the sensor is 400-1100 nm thus it covers the visible range (400-780 nm)
      and the short-wave near infrared (780-1100 nm). Chemometric techniques were
      applied with the purpose of obtaining a predictive model for each parameter
      correlating the spectra obtained by the sensor with the parameters analysed in
      the laboratory. The models were developed by Partial Least Squares Regression
      (PLS) obtaining one model for each parameter. The raw milk samples used in this
      work were provided by CAPSA (Asturias, Spain).

PMID- 22980870
TI  - Comparative study of the oxidative and physical stability of liposomal and
      nanoliposomal polyunsaturated fatty acids prepared with conventional and Mozafari
      methods.
AB  - The relative oxidative stability of freshly prepared and stored liposomal and
      nanoliposomal systems of docosahexaenoic acid (DHA, 22:6 n-3) and
      eicosapentaenoic acid (EPA, 20:5 n-3) were investigated. The effects of organic
      solvents on the oxidative stability of liposomal polyunsaturated fatty acids
      (PUFAs) produced by two methods, the Bangham thin-film hydration (conventional
      rotary evaporation method and using organic solvents) and Mozafari (direct
      hydration and without using organic solvents) methods, were compared. The highest
      physicochemical stability was observed in PUFA liposomes prepared by the Mozafari
      method, followed by conventional liposomes and bulk PUFAs. There was no
      significant change in physicochemical stability during 10 months of cold storage
      (4 degrees C) in the dark. Moreover, the comparison between liposomes (>200 nm)
      and nanoliposomes (50-200 nm) revealed that the surface charge, physical
      stability and oxidative stability of liposomal PUFAs increased as the size of the
      liposomes decreased. The differences in the oxidative stability of PUFAs may be
      due to the protective effects of aqueous systems, which indicate the advantage of
      using non-organic solvent (water and CO(2)) techniques in liposome manufacturing.

PMID- 22980871
TI  - Floral, spicy and herbaceous active odorants in Gran Negro grapes from shoulders
      and tips into the cluster, and comparison with Brancellao and Mouraton varieties.
AB  - Within the framework of a more and more competitive market, the opportunity to
      obtain different wines from the same variety cultivated in the same vineyard is
      becoming of increasing importance. In this study the presence of aroma compounds
      in Gran Negro (Vitis vinifera L.) grapes was investigated in order to obtain its
      aroma potential fingerprint taking into consideration the separation of apical
      (tips) and basal (shoulders) berries of the clusters. In the final stages of
      maturation, differences were searched in the probable alcohol content, total
      acidity of the must, as well as in the aromatic composition of skin and flesh
      from shoulder and cluster tip berries. A GC-MS method was used to determine the
      aromatic composition. The obtained results showed that there was variability for
      their aromatic composition. These results are promising for those wine cellars
      that are considering the separation of berries from tips and shoulders of the
      clusters for the elaboration of wines with different qualities. For the berries
      from the tips of the clusters, aromatic alcohols and volatile phenols were mainly
      found in the flesh (15 and 2 times higher than in the skin, respectively);
      whereas aldehydes and C6 alcohols were mainly in the skin (4 and 3 times higher
      than in the flesh, respectively). For this reason, it could be recommended to
      separate berry skin before enzymatic maceration of the berry flesh must. For the
      berries from the shoulders of the clusters, the group of volatile phenols showed
      2 times more concentration in the skin than in the flesh; it could be recommended
      to maintain berry skin during enzymatic maceration of the must. Overall, the tips
      showed a 40% lower level of C6 alcohols (contributing to herbaceous nuances).
      These results from Gran Negro were compared with those of Brancellao and Mouraton
      cultivars.

PMID- 22980872
TI  - Anti-oxidative analysis, and identification and quantification of anthocyanin
      pigments in different coloured rice.
AB  - Anthocyanin pigments in coloured rice cultivars were isolated and identified
      using high-performance liquid chromatography techniques. Two black rice cultivars
      (Asamurasaki, Okunomurasaki) contained three major anthocyanins: cyanidin-3
      glucoside, peonidin-3-glucoside and malvidin. Chinakuromai (black) rice
      additionally contained a fourth anthocyanin, petunidin-3-glucoside. Four red rice
      cultivars contained only malvidin. The total anthocyanin content varied greatly
      among black rice cultivars (79.5-473.7 mg/100g), but was lower in red rice (7.9
      34.4 mg/100g). Total phenolic content was similar between red (460.32-725.69
      mg/100g) and black (417.11-687.24 mg/100g) rice. The oxygen radical absorbing
      capacity was ranked as follows: red (69.91-130.32 MUmol Trolox/g)>black (55.49
      64.85 MUmol Trolox/g)>green (35.32 MUmol Trolox/g)>white (21.81 MUmol Trolox/g)
      rice. The antioxidant capacity resulted mainly from the seed capsule, not the
      endosperm. The anthocyanin pigments contributed little to the total antioxidant
      capacity of red (0.03-0.1%) and black (0.5-2.5%) rice cultivars. Hence, the
      antioxidant capacity is derived mainly from other phenolic compounds.

PMID- 22980873
TI  - A single extraction and HPLC procedure for simultaneous analysis of phytosterols,
      tocopherols and lutein in soybeans.
AB  - A saponification/extraction procedure and high performance liquid chromatography
      (HPLC) analysis method were developed and validated for simultaneous analysis of
      phytosterols, tocopherols and lutein (a carotenoid) in soybeans. Separation was
      achieved on a phenyl column with a ternary, isocratic solvent system of
      acetonitrile, methanol and water (48:22.5:29.5, v/v/v). Evaporative light
      scattering detection (ELSD) was used to quantify beta-sitosterol, stigmasterol,
      campesterol, and alpha-, delta- and gamma-tocopherols, while lutein was
      quantified with visible light absorption at 450 nm. Peak identification was
      verified by retention times and spikes with external standards. Standard curves
      were constructed (R(2)>0.99) to allow for sample quantification. Recovery of the
      saponification and extraction was demonstrated via analysis of spiked samples.
      Also, the accuracy of results of four soybeans using the described saponification
      and HPLC analytical method was validated against existing methods. This method
      offers a more efficient alternative to individual methods for quantifying lutein,
      tocopherols and sterols in soybeans.

PMID- 22980874
TI  - Elemental content of commercial 'ready to-feed' poultry and fish based infant
      foods in the UK.
AB  - The study reported herein was conducted in order to establish the concentration
      of 20 essential and non-essential elements in a representative range of
      commercial infant foods in the UK targeted for infants aged between 6-12 months.
      The primary objective of this study was to examine the nutritive values and
      safety of such complementary infant foods on the UK market in relation to dietary
      and safety guidelines. Quantitative analyses were conducted on eight different
      products representing four popular brands (poultry and fish based) of ready to
      feed infant foods currently on sale in the UK. Six essential elements, namely:
      calcium, iron, magnesium, potassium, sodium and zinc were determined by ICP-OES.
      The concentrations of six essential trace elements (selenium, molybdenum, cobalt,
      copper, chromium, manganese) and eight non-essential, potentially toxic, elements
      (arsenic, barium, nickel, cadmium, antimony, lead, mercury, aluminium) were
      determined by ICP-MS due to the higher sensitivity required. The total daily
      intakes of essential and trace elements from the consumption of such products
      were then estimated, based on the results of this study, and were referenced to
      the Recommended Nutrient Intake (RNI) values and safety guidelines for 6-9 months
      old children. Based on these comparisons the concentration of essential, except
      for potassium, and trace elements were found to be inadequate in meeting the RNI.
      In terms of the risk of exposure to toxicity, the concentration of toxic elements
      in ready to feed products analysed in this study, were not considered to be of
      concern. These results suggest that commercial complementary infant foods on the
      UK market may not contain minimum levels of minerals required for labelling
      declaration of micronutrient content (Commission Directive 2006/125/EC). This
      provides opportunities and scope for product optimisation to improve their
      nutritive value.

PMID- 22980875
TI  - Screening and quantitative analysis of antioxidants in the fruits of Livistona
      chinensis R. Br using HPLC-DAD-ESI/MS coupled with pre-column DPPH assay.
AB  - In this study, a high performance liquid chromatography-photo diode array
      detection-electrospray ionization tandem mass spectrometry (HPLC-DAD/ESI-MS) with
      pre-column DPPH assay is developed for screening the antioxidant components in
      the fruits of Livistona chinensis R. Br. Accordingly, six antioxidative
      flavonoids are identified as orientin, isoorientin, vitexin, isovitexin,
      isorhamnetin-3-O-glucoside and tricin in methanolic extract of L. chinensis
      fruits, based on their mass spectra and fragmentation patterns. To the best of
      our knowledge, orientin, isoorientin, isovitexin and isorhamnetin-3-O-glucoside
      were found firstly in this plant. The free radical scavenging activity of the six
      antioxidants found is further examined by off-line DPPH assay. The results
      indicated that the free radical scavenging activity of orientin and isoorientin
      are stronger than those of two antioxidative drugs, vitamin C and baicalin. In
      addition, an HPLC-DAD method is firstly established for simultaneous
      determination of the six antioxidants in L. chinensis fruits. Tricin was found to
      be the major component in L. chinensis fruits.

PMID- 22980876
TI  - Quantification of dabsylated di- and tri-peptides in fermented milk.
AB  - An improved HPLC method using pre-column dabsyl chloride derivatisation for the
      separation and quantification of antihypertensive di- and tri-peptides in
      fermented milk products was established. The dabsylated peptides Val-Pro-Pro
      (VPP), Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Phe-Pro (FP) were separated on a
      C18-column coupled to UV/VIS and mass spectrometric detector, respectively. Due
      to the derivatisation of the peptides, an HPLC base line separation was achieved
      and the peak width was improved. The VIS-spectrometry did not allow a good
      quantification of these peptides since more than one peptide co-eluted under one
      single peak. In contrast applying LC-ESI-MS with a single quadrupole much better
      quantification of the dabsylated peptides was done. In Evolus(r) (Valio Ltd.,
      Finland), a fermented milk drink, 6.9 mg L(-1) for VPP, 6.1 mg L(-1) for IPP, 0.8
      mg L(-1) for LPP and 3.2 mg L(-1) for FP were determined. In fermented
      reconstituted milk (Lactobacillus helveticus, 37 degrees C, 48 h) lower
      concentrations of these peptides were determined (0.7, 0.6, 0.0 and 2.2 mg L(-1),
      respectively).

PMID- 22980877
TI  - Polyphenol and glycoalkaloid contents in potato cultivars grown in Luxembourg.
AB  - The polyphenol (phenolic acids, flavanols and flavonols) and glycoalkaloid (alpha
      chaconine and alpha-solanine) contents of potato tubers grown in Luxembourg were
      analyzed by UPLC-DAD and HPLC-MS/MS separately in peel (approx. 2mm), outer
      (approx. 1cm) and inner flesh. Polyphenol contents decreased from the peel via
      the outer to the inner flesh and differed among the cultivars. The cultivars
      Vitelotte and Luminella had the highest polyphenol contents (5202 and 572 MUg/g
      dry weight (DW) in the outer flesh), whereas Charlotte and Bintje had the lowest
      contents (19.5 and 48.0 MUg/g DW). Chlorogenic acid and its isomers (neo- and
      cryptochlorogenic acid) were the major polyphenols. Glycoalkaloid contents were
      highest in the peel and lowest in the inner flesh, values in the flesh were below
      guideline limits in all cultivars. In conclusion, potatoes contribute to the
      daily intake of polyphenols and their consumption, thereby, may have positive
      effects on health.

PMID- 22980878
TI  - The use of wavelength dispersive X-ray fluorescence and discriminant analysis in
      the identification of the elemental composition of cumin samples and the
      determination of the country of origin.
AB  - Sixteen elements found in 33 cumin spice samples from China, India, Syria, and
      Turkey were analysed by wavelength dispersive X-ray fluorescence (WDXRF)
      spectroscopy using the commercially available Bruker - AXS S4 Explorer for the
      purpose of using the elements to discriminate among country of origin. Pellets
      were prepared of the samples and elemental concentrations calculated from
      calibration curves constructed using four National Institute of Standards and
      Technology (NIST) standards. A separate NIST tomato standard (1573a) was used as
      a validation check, while the WDXRF data for six of the cumin samples was further
      validated using inductively coupled plasma-atomic emission spectroscopy (ICP
      AES). The elements measured included Ca, Mg, K, P, S, Al, Ba, Br, Cl, Fe, Na, Mn,
      Rb, Sr, Cu, and Zn and were detected in the range from an average mean of 4.3 mg
      kg(-1) for Ba up to 19223.8 mg kg(-1) for K. Analysis of variance (ANOVA) was
      used to determine which elemental concentrations were statistically different
      from one another, and discriminant analysis was used to classify the cumin
      samples by country of origin. Using only eight elements (Ca, Mg, K, Fe, Na, Mn,
      Sr, and Zn) we were able to differentiate among cumin samples from four different
      geographic origins. Validation of the model with the validation set yielded
      87.50% accuracy. Successful discrimination with just eight elements will allow
      for higher throughput in the screening of cumin samples using WDXRF for origin
      verification in less time.

PMID- 22980879
TI  - Fast simultaneous determination of free and conjugated isoflavones in soy milk by
      UHPLC-UV.
AB  - Ultra high pressure liquid chromatography (UHPLC) has become a widely used
      technique in separation science as it can shorten analysis time while maintaining
      resolution and increasing sensitivity. Here we developed a UHPLC method with UV
      detection for the simultaneous determination of isoflavone aglycones (daidzein,
      glycitein and genistein), their corresponding glycoside forms (daidzin, glycitin
      and genistin), and acetyl and malonyl conjugate forms of glycosides
      (malonyldaidzin, malonylglycitin, malonylgenistin, acetyldaidzin, acetylglycitin,
      acetylgenistin) in soy milk. The method allowed reliable determinations of 12
      isoflavones in less than 8 min of chromatographic elution. It provided a
      satisfactory linearity ranging from 0.1 to 5mg/L, except for daidzin and
      genistin, for which it ranged from 0.1 to 10mg/L. In addition, it showed
      acceptable chromatographic sensitivity, with a detection limit lower than 0.05
      mg/L and a determination limit below 0.2mg/L. The precision, in terms of relative
      standard deviation, was lower than 5% and the accuracy, as mean recovery, was
      greater than 95%. Total isoflavone content in commercial soy milk samples (n=8)
      ranged from 1805.22 to 3195.59 mg/kg dw. Genistin and Daidzin were the major
      isoflavones in all samples. The proportion of aglycones, beta-glucosides, and
      acetyl and malonyl glucosides differed among the samples. beta-Glucosides were
      identified as the predominant forms.

PMID- 22980880
TI  - A new variant of antimetabolic protein, arcelin from an Indian bean, Lablab
      purpureus (Linn.) and its effect on the stored product pest, Callosobruchus
      maculatus.
AB  - The anti-metabolic or insecticidal gene, arcelin (Arl) was isolated, cloned and
      sequenced using sequence specific degenerate primers from the seeds of Lablab
      purpureus collected from the Western Ghats, Tamil Nadu, India. The L. purpureus
      arcelin nucleotide sequence was homologous to Arl-3 and Arl-4 alleles from
      Phaseolus spp. The protein it encodes has 70% amino acid identity with the amino
      acid sequences of Arl-3I, Arl-3III, Arl-4 precursor, Arl-4 and Arl-4I. The
      partially purified arcelin from the seeds of L. purpureus using an artificial
      diet confirmed the complete retardation of development of the stored product pest
      Callosobruchus maculatus at 0.2% w/w arcelin-incorporated artificial seeds.

PMID- 22980881
TI  - Vegetable oil blends with alpha-linolenic acid rich Garden cress oil modulate
      lipid metabolism in experimental rats.
AB  - Vegetable oil blends with modified fatty acid profile are being developed to
      improve n-6/n-3 polyunsaturated fatty acid (PUFAs) ratio in edible oils. The
      objective of this study is to develop vegetable oil blends with alpha-linolenic
      acid (ALA) rich Garden cress oil (GCO) and assess their modulatory effect on
      lipid metabolism. Sunflower oil (SFO), Rice bran oil (RBO), Sesame oil (SESO)
      were blended with GCO at different ratios to obtain n-6/n-3 PUFA ratio of 2.3
      2.6. Native and GCO blended oils were fed to Wistar rats at 10% level in the diet
      for 60 days. Serum and liver lipids showed significant decrease in Total
      cholesterol (TC), Triglyceride (TG), LDL-C levels in GCO and GCO blended oil fed
      rats compared to native oil fed rats. ALA, EPA, DHA contents were significantly
      increased while linoleic acid (LA), arachidonic acid (AA) levels decreased in
      different tissues of GCO and GCO blended oils fed rats. In conclusion, blending
      of vegetable oils with GCO increases ALA, decreases n-6 to n-3 PUFA ratio and
      beneficially modulates lipid profile.

PMID- 22980882
TI  - A forgotten vegetable (Smyrnium olusatrum L., Apiaceae) as a rich source of
      isofuranodiene.
AB  - Smyrnium olusatrum, well known as wild celery or Alexanders, is a biennial herb
      belonging to the Apiaceae and used for many centuries as an edible vegetable
      because of the aromatic flavour of its parts. Its use on the table has decreased
      since the Middle Ages when it was replaced by common celery (Apium graveolens).
      In the present work the composition of the essential oils obtained by
      hydrodistillation of various plant parts was investigated by gas chromatography
      (GC-FID and GC-MS), while quantitation of a heat-sensitive compound,
      isofuranodiene, known for its anticancer activity, and of its Cope rearrangement
      product curzerene, was achieved by HPLC-DAD. All essential oils were composed
      mainly of furanosesquiterpenoids (54.1-76.2%) with isofuranodiene (19.5-45.8%) as
      the main constituent. Results showed that GC analysis provides underestimation
      (up to five times) of isofuranodiene levels in essential oils and that curzerene
      could be considered an artifact since it is produced during heating of plant
      material, occurring during hydrodistillation.

PMID- 22980883
TI  - Effect of oxygen and lipid supplementation on the volatile composition of
      chemically defined medium and Chardonnay wine fermented with Saccharomyces
      cerevisiae.
AB  - Oxygen or lipids are required to complete stressful alcoholic fermentation. Lack
      of these nutrients can inhibit sugar uptake and growth, which leads to incomplete
      or 'stuck' fermentation. Oxygen or lipids supplementation not only restores yeast
      fermentative activity and also affects formation of yeast volatile metabolites.
      To clarify the effect of oxygen and lipid supplementation on the formation of
      flavour active metabolites during wine fermentation, we evaluated the addition of
      these two nutrients to chemically defined grape juice and filter clarified
      Chardonnay must. Lipid addition increased the concentration of esters, higher
      alcohols and volatile acids, whereas oxygen increased the concentration of higher
      alcohols and altered the proportion of acetate to ethyl esters and the proportion
      of branch-chain acids to medium-chain fatty acids. Combined addition of lipids
      and oxygen showed an additive effect on concentration of higher alcohols whereas
      oxygen suppressed the enhancing effect of lipids on formation of esters and
      volatile acids. Our results demonstrate the potential of lipid and oxygen
      supplementation for the manipulation of wine aroma in white wine fermentation.

PMID- 22980884
TI  - Biological evaluation of coumarin derivatives as mushroom tyrosinase inhibitors.
AB  - A series of coumarin derivatives were synthesised and their inhibitory effects on
      the diphenolase activity of mushroom tyrosinase were evaluated. The results
      showed that some of the synthesised compounds exhibited significant inhibitory
      activities. Especially, 2-(1-(coumarin-3-yl)ethylidene)hydrazinecarbothioamide
      bearing thiose-micarbazide group exhibited the most potent tyrosinase inhibitory
      activity with IC(50) value of 3.44MUM. The inhibition mechanism analysis of 2-(1
      (coumarin-3-yl)-ethylidene)hydrazinecarbothioamide and 2-(1-(6-chlorocoumarin-3
      yl)ethylidene)-hydrazinecarbothioamide demonstrated that the inhibitory effects
      of the compounds on the tyrosinase were irreversible. Preliminary structure
      activity relationships' (SARs) analysis suggested that further development of
      such compounds might be of interest.

PMID- 22980885
TI  - The application of high resolution diffusion NMR to the analysis of manuka honey.
AB  - The application of DOSY (Diffusion Ordered SpectroscopY) NMR as a technique for
      the virtual separation of key components of manuka honey and the implications for
      future discriminatory analysis of honey types is reported for the first time. The
      scope and the limitations of DOSY NMR are considered using the recently conceived
      DOSY Tool Box processing software and preliminary anti-bacterial data for the
      different honey types is reported.

PMID- 22980886
TI  - Oxidative degradation and non-enzymatic browning due to the interaction between
      oxidised lipids and primary amine groups in different marine PL emulsions.
AB  - Due to the beneficial health effects of marine phospholipids (PL) there is an
      increasing industrial interest in using them for nutritional applications
      including emulsified foods. This study was undertaken to investigate both
      oxidative and hydrolytic stability of marine PL emulsions in relation to the
      chemical composition of the marine PL used. Moreover, non-enzymatic browning
      reactions were also investigated. Emulsions were prepared by high pressure
      homogenizer using different concentrations and sources of marine PL. In some
      formulations, fish oil was added in order to study the effect of increasing
      levels of triglycerides in the emulsions. The oxidative and hydrolytic stability
      of emulsions was investigated through measurement of peroxide value, free fatty
      acids, and (31)P NMR during storage at 2 degrees C for up to 32 days. The
      oxidative stability of marine PL emulsions during storage was further
      investigated through the measurement of secondary volatile compounds by solid
      phase microextraction (SPME) and dynamic headspace (DHS) connected to gas
      chromatography (GC-MS). Non-enzymatic browning reactions were investigated
      through the measurement of Strecker derived volatiles, colour changes and pyrrole
      content. The results suggested that the oxidative stability of marine PL
      emulsions was significantly influenced by the chemical composition and the
      concentration of marine PL used to prepare them. Emulsions with good oxidative
      stability could be prepared from marine PL of high purity and high content of PL
      and antioxidant and low TAG content.

PMID- 22980887
TI  - Rapid detection and quantification of dietary mutagens in food using mass
      spectrometry and ultra performance liquid chromatography.
AB  - Meat is universally consumed as human diet across the globe. More than 24
      different types of food mutagens have been identified till date from cooked meat
      products. Their study therefore assumes a greater significance from the point of
      view of the worldwide problem of cancer. Using rapid ultra performance liquid
      chromatography (UPLC) and MALDI-TOF MS the detection and quantification of two
      main heterocyclic aromatic amines (HAAs) - MeIQx (2-amino-3,8 dimethylimidazo 4,5
      f quinoxaline) and PhIP (2-amino-1-methyl-6 phenylimidazo (4,5-b pyridine) has
      been achieved in beef, mutton, chicken and fish samples subjected to a range of
      time duration and temperature. Temperature and duration of heating directly
      affect the generation and amount of MeIQx and PhIP. MeIQx was generated at 180
      degrees C. PhIP was not formed before 240 degrees C except in chicken. MeIQx was
      found in higher amounts in chicken 128.32 +/- 0.452 ng/g and in fish 44.06 +/-
      1.499 ng/g while PhIP was found in higher amount in mutton 40.21 +/- 0.650 ng/g.

PMID- 22980888
TI  - Secondary metabolites from the unripe pulp of Persea americana and their
      antimycobacterial activities.
AB  - The fruits of Persea americana (Avocado) are nowadays used as healthy fruits in
      the world. Bioassay-guided fractionation of the active ethyl acetate soluble
      fraction has led to the isolation of five new fatty alcohol derivatives,
      avocadenols A-D (1-4) and avocadoin (5) from the unripe pulp of P. americana,
      along with 12 known compounds (6-17). These structures were elucidated by
      spectroscopic analysis. Among the isolates, avocadenol A (1), avocadenol B (2),
      (2R,4R)-1,2,4-trihydroxynonadecane (6), and (2R,4R)-1,2,4-trihydroxyheptadec-16
      ene (7) showed antimycobacterial activity against Mycobacterium tuberculosis
      H(37)R(V)in vitro, with MIC values of 24.0, 33.8, 24.9, and 35.7 MUg/ml,
      respectively.

PMID- 22980889
TI  - Antioxidant capacity and anthocyanin profile of sour cherry (Prunus cerasus L.)
      juice.
AB  - The antioxidant capacities, total polyphenolic content and monomeric anthocyanin
      content of eleven types of sour cherry juice obtained from different varieties of
      sour cherries were investigated. Antioxidant capacity, total polyphenolic content
      and monomeric anthocyanin contents of the juices were within the ranges 20.0-37.9
      mmol/L, 1510-2550 and 350.0-633.5mg/L, respectively. The main anthocyanin
      compound in sour cherry juice was cyanidin-3-glucosylrutinoside at concentrations
      between 140.3 and 320.9 mg/L. Cyanidin-3-glucosylrutinoside was followed by
      cyanidin-3-rutinoside within a concentration range of 25.5-85.5mg/L. Cyanidin-3
      sophoroside and cyanidin-3-glucoside contents were relatively low (2.6-21.5 and
      2.0-9.9 mg/L). Anthocyanin capacity and total polyphenol content were fairly well
      correlated (r=0.742, p<0.01), whereas the correlation between antioxidant
      capacity and monomeric anthocyanin content was insignificant (r=0.423, p>0.05).
      The correlation between antioxidant capacity - cya-3-glucosylrutinoside (r=0.606,
      p<0.01) and antioxidant capacity - cya-3-rutinoside (r=0.628, p<0.01) was
      significant.

PMID- 22980890
TI  - Effects of tea polyphenol coating combined with ozone water washing on the
      storage quality of black sea bream (Sparus macrocephalus).
AB  - The present research evaluated the effects of tea polyphenol (TP) combined with
      ozone water (O(3)) on the quality of black sea bream (Sparus macrocephalus) over
      a period of 15 days storage at 4 degrees C. A solution of TP (0.2%, w/v) was used
      to coat the fish after washing with ozone water (1mg/L). Fish physicochemical
      (pH, K value, peroxide value, thiobarbituric acid, total volatile basic nitrogen,
      trimethylamine, texture, and colour), sensory, and bacteriological
      characteristics were all analysed. TP+O(3) treatment effectively reduced
      nucleotide breakdown, lipid oxidation, protein decomposition, and microbial
      growth, and maintained better characteristics of texture, colour, and sensory
      compared with the control. The efficiency of TP+O(3) treatment was also better
      than that of TP treatment or O(3) treatment alone. Therefore, tea polyphenol
      coating combined with ozone water prewashing may be a promising method of
      maintaining the storage quality of black sea bream and of extending fish post
      mortem shelf-life during 4 degrees C storage.

PMID- 22980891
TI  - Impact of olive oil phenolic concentration on human plasmatic phenolic
      metabolites.
AB  - Three different functional phenol-enriched virgin olive oils (FVOO) were prepared
      with a phenolic content of 250 (L-FVOO), 500 (M-FVOO), and 750 mg (H-FVOO) total
      phenols/kg. In a randomised, cross-over study with 12 healthy volunteers, the
      pharmacokinetics of phenolic biological metabolites was assessed. An increasing
      linear trend was observed for hydroxytyrosol sulfate, the main phenolic
      metabolite quantified in plasma, with C(max) values of 1.35, 3.32, and 4.09
      MUmol/l, and AUC mean values of 263.7, 581.4, and 724.4 MUmol/min for L-FVOO, M
      FVOO, and H-FVOO, respectively. From our data an acute intake of phenol-enriched
      olive oils promotes a dose-dependent response of phenol conjugate metabolites in
      human plasma. Also, we point out for the first time hydroxytyrosol acetate
      sulfate as a main biological metabolite of hydroxytyrosol from olive oil
      ingestion.

PMID- 22980892
TI  - Monitoring and risk assessment of pesticide residues in yuza fruits (Citrus junos
      Sieb. ex Tanaka) and yuza tea samples produced in Korea.
AB  - The objective of this study was to establish an analytical method to measure
      pesticides used to cultivate yuza (Citrus junos Sieb. ex Tanaka) and to analyze
      pesticide residue levels of yuza and yuza tea samples. Risk assessments were also
      performed by calculating estimated daily intake (EDI) and acceptable daily intake
      (ADI). An excellent linear correlation was achieved with coefficient correlation
      values of 0.9750-0.9999. Percent recoveries were 80.4-109.9% for most pesticides
      with a <6.9% relative standard deviation (RSD). The limits of quantification for
      the method were 0.10-0.67 MUg/ml. The RSD of intra-day and inter-day variability
      was <15.3%. Seven pesticides in yuza (n=80) and yuza tea (n=75) were analyzed
      with the optimized analytical method. Acequinocyl, spirodiclofen and carbendazim
      were detected in yuza samples in the concentration range of 0.07-0.15 MUg/g, 0.11
      1.89 MUg/g, and 0.03-5.15 MUg /g, respectively, whereas chlorpyrifos, prothiofos,
      phosalone, and deltamethrin were not detected in yuza or yuza tea. The
      concentrations of acequinocyl, spirodiclofen and carbendazim ranged from 0.18
      1.05 MUg/g, 0.13-0.29 MUg/g, and 0.17-2.36 MUg/g, respectively, in yuza tea
      samples. The percent ratios of EDI to ADI for acequinocyl, spirodiclofen, and
      carbendazim were 24.6%, 22.7%, and 58.5%, respectively.

PMID- 22980893
TI  - The role of light, temperature and wine bottle colour on pigment enhancement in
      white wine.
AB  - Pigmentation enhancement in a Chardonnay wine with high flavan-3-ol concentration
      was examined by irradiating the wine under controlled conditions. Heating the
      wine in darkness required temperatures in excess of 50 degrees C before enhanced
      pigmentation became apparent. It was found that ultraviolet and, to a lesser
      extent, low wavelength visible light contributed to pigment production. The
      development of pigmentation depended on wine bottle glass colour: Flint>Arctic
      Blue>French Green>Antique Green. This is in agreement with the transmission
      characteristics of the bottles with even the darkest (Antique Green) allowing the
      transmission of some ultraviolet light. Riboflavin, when added to the wine,
      degraded rapidly when exposed to radiation <400 nm. The degradation of riboflavin
      and the onset of colour development depended on the actual amounts as well as the
      ratio of riboflavin to flavan-3-ol, suggesting that a complex series of reactions
      are occurring. A degradation product of riboflavin may be contributing to the
      increase in absorbance in the visible region observed during light exposure.

PMID- 22980894
TI  - Identification of the flavonoids in mungbean (Phaseolus radiatus L.) soup and
      their antioxidant activities.
AB  - Mung bean soup (MBS) has been traditionally taken as a kind of health food in
      China. To learn the mechanisms underlying its health benefits, antioxidant
      capacities of the soup prepared with three cultivars of mung bean were measured.
      The highest DPPH radical scavenging or ferric reducing activity was observed in
      soup of mung bean cv. Huang. The MBS of cv. Huang and Mao exhibited higher
      ABTS(+) reducing activities than MBS of cv. Ming. The two major flavonoids in the
      MBS were purified and identified as vitexin and isovitexin, respectively.
      Modeling samples containing vitexin and isovitexin at the same levels as them in
      the MBS were prepared to assess their antioxidant contributions in the MBS. Our
      results showed that antioxidant capacities of the MBS mainly derived from vitexin
      and isovitexin, these flavonoids accounted for the most of total DPPH radicals
      scavenging, ferric reducing and ABTS(+) reducing scavenging activities in MBS of
      all the three cultivars.

PMID- 22980895
TI  - Discrimination of mineral waters by electronic tongue, sensory evaluation and
      chemical analysis.
AB  - Mineral, spring and tap water samples of different geographical origins (7
      classes) were distinguished by various methods, such as sensory evaluation,
      electronic tongue measurement, inductively coupled plasma atomic emission
      spectroscopy and ion chromatography. Samples from the same geographical origin
      were correctly classified by chemical analysis and electronic tongue (100%), but
      it was found that only 80% classification rate can be achieved by sensory
      evaluation. Different water brands (different brand names) from the same
      geographical origin did not show definite differences, as expected. Forward
      stepwise algorithm selected three chemical parameters namely, chloride (Cl(-)),
      sulphate (SO(4)(2-)) and magnesium (Mg) content and two electronic tongue sensor
      signals (ZZ and HA) to discriminate according to the geographical origins.

PMID- 22980896
TI  - Dose-dependent effect in the inhibition of oxidative stress and anticlastogenic
      potential of ginger in STZ induced diabetic rats.
AB  - Ginger is an important medicinal herb has numerous bioactive components and is
      used in the management, control and/or treatment of diseases including diabetes
      mellitus. The present study was undertaken to see the dose-response effect of
      ginger and evaluate the possible protective effects of dietary ginger on
      oxidative stress and genotoxicity induced by streptozotocin (STZ) diabetic rats.
      Inbred male Wistar/NIN rats of 8-9 weeks old were treated with 30 mg/kg of STZ.
      Rats were divided into different groups of control, diabetic non-treated, and
      diabetic treated with ginger powder at 0.5%, 1% and 5% respectively. After
      feeding for a month, blood and tissues were collected to see the effect of ginger
      on antioxidant status, DNA damage and bone marrow genotoxicity. In this study
      ginger exerted a protective effect against STZ-induced diabetes by modulating
      antioxidant enzymes and glutathione and down regulating lipid and protein
      oxidation and inhibition in genotoxicity in a dose-response manner.

PMID- 22980897
TI  - Shelf life of powdered Campomanesia adamantium pulp in controlled environments.
AB  - The objective of this study was to evaluate the shelf life of powdered guavira
      pulp obtained by a foam mat drying process. The dehydrated guavira pulp was
      packed into low density polyethylene (LDPE) bags and stored under two controlled
      conditions: environmental (25 degrees C, RH 75%) and accelerated (35 degrees C,
      RH 90%) for 90 days. The shelf life was accompanied by carrying out the following
      analyses every 10 days: moisture content, water activity, vitamin C content, pH
      and titratable acidity. Vitamin C was the quality attribute used to determine the
      shelf life of the product, by determining its degradation kinetics as a function
      of storage time. The linear regression data showed that the vitamin C degradation
      reaction fitted the zero and first order kinetic models. The shelf life of the
      powdered guavira pulp under environmental conditions was approximately 49 days,
      and under accelerated conditions (35 degrees C) 45 days. The Q10 was equal to
      1.09, predicting a shelf life similar to that found under environmental
      conditions. The moisture content for these conditions was 10.0% e 5.4% for 35
      degrees C and 25 degrees C, respectively. The above demonstrate the efficiency of
      the accelerated test in predicting the shelf life of the product.

PMID- 22980898
TI  - Changes in chemical composition and antioxidative properties of rye ginger cakes
      during their shelf-life.
AB  - Changes in chemical composition and antioxidative properties of rye ginger cakes
      during their shelf-life were investigated in this study. In particular, the
      changes in antioxidants content, antioxidative and reducing capacity, and
      Maillard reaction development in rye ginger cakes after long-term storage were
      addressed. Ginger cakes produced according to the traditional and current recipe
      were stored for 5 years at room temperature in a dark place. The total phenolic
      compounds (TPC), inositol hexaphosphate (IP6), reduced (GSH) and oxidised
      glutathione (GSSG) contents, antioxidant and reducing capacity and Maillard
      reaction products (MRPs) were determined in ginger cakes after storage and then
      compared to those measured after baking. After long-term storage a decrease in
      TPC and IP6 contents in cakes was noted. In contrast, an increase in
      antioxidative and reducing capacity of stored cakes was observed. Long-term
      storage induced formation of furosine, advanced and final Maillard reaction
      products and caused changes in both reduced and oxidised forms of glutathione.
      After long-term storage the modest changes in furosine, FAST index and browning
      in ginger cake formulated with dark rye flour may suggest that this product is
      the healthiest among others. Therefore, traditional rye ginger cakes can be
      considered as an example of a healthy food that is also relatively stable during
      long term storage as noted by the small chemical changes observed in its
      composition.

PMID- 22980899
TI  - Measurement of the influence of flavonoids on DNA repair kinetics using the comet
      assay.
AB  - The complexity of DNA repair mechanisms infers that xenobiotics, derived from
      food and medicinal plants, may interfere in the process, activating or inhibiting
      repair. Different flavonoids were investigated, at the highest non-toxic
      concentration, for their capacity to modulate DNA repair 12, 24 and 48 h after a
      non-reactive oxygen species (ROS) treatment involving ethylmethanesulfonate (2mM;
      2h). After 12h, DNA fragmentation is substantially increased by quercetin; this
      effect disappears at subsequent sampling times. At 24h, fragmentation is reduced
      in the presence of apigenin and slightly increased by sakuranetin. None of the
      flavonoids tested inhibited repair, which seems complete at 48 h. Ex vivo comet
      experiments were then performed to assess the excision capabilities of protein
      extracts obtained from flavonoid-treated cells. Quercetin increases non-specific
      endonuclease activity, apigenin and epicatechin increase the excision of damages
      and sakuranetin increases both non-specific and specific enzymatic activities.
      Combining direct repair and ex vivo experiments yields complementary data that
      may lead to characterizing mechanisms.

PMID- 22980900
TI  - Mediated xanthine oxidase potentiometric biosensors for hypoxanthine based on
      ferrocene carboxylic acid modified electrode.
AB  - A potentiometric enzyme electrode for detection of hypoxanthine (Hx) in fish meat
      is described. The sensor was developed by entrapment of xanthine oxidase (XOD)
      and ferrocene carboxylic acid (Fc) into polypyrrole (PPy) film during
      galvanostatic polymerisation film formation. The responses for Hx were obtained
      in 0-05 M phosphate buffer (pH 7.1) at 0.0 mV vs Ag/AgCl (3M KCl). The optimum
      condition for the formation of PPy-XOD-Fc film include 0.4M PPy, 6.2U/mL XOD, 40
      mM Fc, polymerisation time of 200 s and applied current density of 0-5 mA cm(-2).
      The sensor provides a linear response to Hx in concentration range of 5-20 MUM,
      (r=0.998) and was successfully used for determination of Hx in fish.

PMID- 22980901
TI  - Optimisation for subcritical fluid extraction of 17-methyltestosterone with
      1,1,1,2-tetrafluoroethane for HPLC analysis.
AB  - A simple, rapid and sensitive method was developed for determination of 17alpha
      methyltestosterone in aquatic products by extraction with subcritical 1,1,1,2
      tetrafluoroethane (R134a) extraction and high performance liquid chromatography
      (HPLC). Response surface methodology (RSM) was adopted to optimise extraction
      pressure, temperature and co-solvent volume. The optimum extraction conditions
      predicted within the experimental ranges were as follows: pressure 5 MPa,
      temperature 31 degrees C, and co-solvent volume 3.35ml. The analysis was carried
      out on XDB-C(18) column (4.6 mm * 250 mm, 5 MUm) with the mobile phase
      acetonitrile-water (55:45, v/v), flow rate 0.8 ml/min, temperature 30 degrees C
      and wavelength 245 nm. Good linearity of detection was obtained for 17alpha
      methyltestosterone between concentrations of 50-250 ng/ml, r(2)=0.999. The method
      was validated using samples fortified with 17alpha-methyltestosterone at levels
      of 10, 30 and 50 ng/g, the mean recovery exceeds 90%, and the RSD values were
      less than 10%.

PMID- 22980902
TI  - In vivo and in vitro antidiabetic effects of aqueous cinnamon extract and
      cinnamon polyphenol-enhanced food matrix.
AB  - Cinnamon has a long history of medicinal use and continues to be valued for its
      therapeutic potential for improving metabolic disorders such as type 2 diabetes.
      In this study, a phytochemically-enhanced functional food ingredient that
      captures water soluble polyphenols from aqueous cinnamon extract (CE) onto a
      protein rich matrix was developed. CE and cinnamon polyphenol-enriched defatted
      soy flour (CDSF) were effective in acutely lowering fasting blood glucose levels
      in diet induced obese hyperglycemic mice at 300 and 600 mg/kg, respectively. To
      determine mechanisms of action, rat hepatoma cells were treated with CE and
      eluates of CDSF at a range of 1-25 MUg/ml. CE and eluates of CDSF demonstrated
      dose-dependent inhibition of hepatic glucose production with significant levels
      of inhibition at 25 MUg/ml. Furthermore, CE decreased the gene expression of two
      major regulators of hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase
      and glucose-6-phosphatase. The hypoglycemic and insulin-like effects of CE and
      CDSF may help to ameliorate type 2 diabetes conditions.

PMID- 22980903
TI  - Stilbene levels and antioxidant activity of Vranec and Merlot wines from
      Macedonia: effect of variety and enological practices.
AB  - The content of the stilbenes trans-resveratrol and piceid as well as the
      antioxidant activity of Macedonian red wines from the two main grape varieties
      Vranec and Merlot have been evaluated. The effects of time of maceration, type of
      yeast and the level of sulphur dioxide applied on stilbene content and
      antioxidant activity have been studied. The most important factor in winemaking
      technology is the maceration time since the highest concentrations of trans
      resveratrol, piceid and highest antioxidant activity were found following 6 and
      10 days of maceration. Concerning the yeast type, higher concentrations of trans
      resveratrol and piceid have been obtained with French yeast "Levuline CHP" in
      comparison to Macedonian yeast "Vinalco". In contrast, the higher antioxidant
      activity of wines from both varieties of grapes was observed by application of
      Macedonian yeast "Vinalco".

PMID- 22980904
TI  - Bathochromic and stabilising effects of sugar beet pectin and an isolated pectic
      fraction on anthocyanins exhibiting pyrogallol and catechol moieties.
AB  - The formation of anthocyanin-metal chelates, exhibiting intense blue colours was
      monitored over a period up to 10 weeks. Evaluating normalised absorption spectra
      in the range of 580-700 nm and their proportion of the total area under the curve
      (AUC), provided information about the blue colour hue, intensity and stability.
      Colour stability in model solutions containing commercial sugar beet pectin or an
      isolated pectic polysaccharide fraction (PPF) therefrom, both being naturally
      enriched in aluminium and ferric ions, was assessed in a pH range of 3.6-7.0. The
      pectic structures stabilised anthocyanin-metal chelates, and thus blue colours by
      efficiently preventing complex precipitation. Highest bathochromic shifts and
      most intense blue colours were observed in PPF model solutions containing
      delphinidin-3-glucoside (Dpd-3-glc), exhibiting a pyrogallol moiety in the
      flavylium B-ring, compared to cyanidin- (Cyd-3-glc) and petunidin-3-glucoside
      (Pet-3-glc), both carrying a catechol substituted B-ring. Hue and intensity of
      the blue colour at pH 5.0 were only insignificantly influenced by the buffer
      system except for citrate and phosphate buffers, which both annihilated
      anthocyanin-metal chelate formation. The blue colours faded following first order
      kinetics. Best stabilities as deduced from storage experiments performed at 20 +/
      2 degrees C in the dark were observed for Dpd-3-glc. In contrast, Cyd-3-glc
      displayed shortened half-life values, whereas blue Pet-3-glc chelates decomposed
      rapidly. These results demonstrate that the solubilisation of anthocyanin-metal
      chelates by pectic structures is a promising option for developing water soluble
      natural blue food colourants.

PMID- 22980905
TI  - Fish protein hydrolysates: proximate composition, amino acid composition,
      antioxidant activities and applications: a review.
AB  - The fish processing industry produces more than 60% by-products as waste, which
      includes skin, head, viscera, trimmings, liver, frames, bones, and roes. These by
      product wastes contain good amount of protein rich material that are normally
      processed into low market-value products, such as animal feed, fish meal and
      fertilizer. In view of utilizing these fish industry wastes, and for increasing
      the value to several underutilised fish species, protein hydrolysates from fish
      proteins are being prepared by several researchers all over the world. Fish
      protein hydrolysates are breakdown products of enzymatic conversion of fish
      proteins into smaller peptides, which normally contain 2-20 amino acids. In
      recent years, fish protein hydrolysates have attracted much attention of food
      biotechnologists due to the availability of large quantities of raw material for
      the process, and presence of high protein content with good amino acid balance
      and bioactive peptides (antioxidant, antihypertensive, immunomodulatory and
      antimicrobial peptides).

PMID- 22980906
TI  - Antioxidative and functional properties of protein hydrolysate from defatted
      skipjack (Katsuwonous pelamis) roe.
AB  - Antioxidative and functional properties of protein hydrolysate from defatted
      skipjack (Katsuwonous pelamis) roe, hydrolysed by Alcalase 2.4 L (RPH) with
      different degrees of hydrolysis (DH) at various concentrations were examined. As
      DH increased, the reduction of DPPH, ABTS radicals scavenging activities and
      reducing power were noticeable (p<0.05). The increases in metal chelating
      activity and superoxide scavenging activity were attained with increasing DH
      (p<0.05). However, chelating activity gradually decreased at DH above 30%. All
      activities except superoxide anion radical scavenging activity increased as the
      concentration of hydrolysate increased (p<0.05). Hydrolysis using Alcalase could
      increase protein solubility to above 80% over a wide pH range (2-10). The highest
      emulsion ability index (EAI) and foam stability (FS) of hydrolysates were
      observed at low DH (5%) (p<0.05). Concentrations of hydrolysates determined
      interfacial properties differently, depending on DH. The molecular weight
      distribution of RPH with 5%DH (RPH5) was determined using Sephadex G-75 column.
      Two major peaks with the molecular weight of 57.8 and 5.5kDa were obtained.
      Fraction with MW of 5.5 had the strongest metal chelating activity and ABTS
      radical scavenging activity. The results reveal that protein hydrolysates from
      defatted skipjack roe could be used as food additives possessing both antioxidant
      activity and functional properties.

PMID- 22980907
TI  - Fetuin-A triggers the secretion of a novel set of exosomes in detached tumor
      cells that mediate their adhesion and spreading.
AB  - Our goal in this study was to define the mechanisms by which fetuin-A mediates
      the adhesion of tumor cells. The data show that in the absence of fetuin-A,
      detached tumor cells secrete exosomes that contain most of the known exosomal
      associated proteins but lack the capacity to mediate cellular adhesion. In the
      presence of fetuin-A, the cells secrete exosomes, which contain, in addition to
      the other exosomal proteins, fetuin-A, plasminogen and histones. These exosomes
      mediate adhesion and cell spreading. Plasminogen is a participant in this novel
      adhesion mechanism. The data suggest that these exosomes play a role in tumor
      progression.

PMID- 22980908
TI  - Hydration of geosynthetic clay liners from clay subsoil under simulated field
      conditions.
AB  - Use of Geosynthetic Clay Liners (GCLs) in landfill barrier design has been the
      focus of recent studies investigating their ability to prevent contaminant
      transport to groundwater. In this paper, the hydration of two GCL products placed
      in contact with clay subsoils at different initial moisture contents is described
      under both isothermal conditions at room temperature, and daily thermal cycles.
      The rate of hydration of the GCL and its final equilibrium moisture content were
      significantly influenced by the amount of moisture made available to it through
      the subsoil. The two types of GCLs were also found to exhibit different hydration
      behaviors under similar experimental conditions. The study revealed that GCLs
      undergoing daily thermal cycles absorbed much less moisture over time than the
      GCLs kept at constant room temperature (ratio 1:4). In comparison with other
      types of subsoils, the final equilibrium moisture content attained by the GCL
      from clay subsoil was significantly less than that for sand subsoil.

PMID- 22980909
TI  - Hydraulic conductivity study of compacted clay soils used as landfill liners for
      an acidic waste.
AB  - Three natural clayey soils from Tunisia were studied to assess their suitability
      for use as a liner for an acid waste disposal site. An investigation of the
      effect of the mineral composition and mechanical compaction on the hydraulic
      conductivity and fluoride and phosphate removal of three different soils is
      presented. The hydraulic conductivity of these three natural soils are 8.5 * 10(
      10), 2.08 * 10(-9) and 6.8 * 10(-10)m/s for soil-1, soil-2 and soil-3,
      respectively. Soil specimens were compacted under various compaction strains in
      order to obtain three wet densities (1850, 1950 and 2050 kg/m(3)). In this
      condition, the hydraulic conductivity (k) was reduced with increasing density of
      sample for all soils. The test results of hydraulic conductivity at long-term
      (>200 days) using acidic waste solution (pH=2.7, charged with fluoride and
      phosphate ions) shows a decrease in k with time only for natural soil-1 and soil
      2. However, the specimens of soil-2 compressed to the two highest densities (1950
      and 2050 kg/m(3)) are cracked after 60 and 20 days, respectively, of hydraulic
      conductivity testing. This damage is the result of a continued increase in the
      internal stress due to the swelling and to the effect of aggressive wastewater.
      The analysis of anions shows that the retention of fluoride is higher compared to
      phosphate and soil-1 has the highest sorption capacity.

PMID- 22980910
TI  - Statistical analysis of optimum Fenton oxidation conditions for landfill leachate
      treatment.
AB  - Optimal operating conditions observed by peer reviewed publications for Fenton
      oxidation of raw and biological and coagulation treated leachates were reviewed
      and statistically analyzed. For the first-stage Fenton oxidation, the optimal pH
      range of 2.5-4.5 was observed for raw and coagulation treated leachates with a
      median pH of 3.0, whereas, for biologically treated leachate the optimum pH range
      was 2.5-6.0 with a median pH of 4.2. Theoretically, the optimal ratio of
      H(2)O(2)/Fe(2+) should be the ratio of rate constants of the reactions between
      OH() radical with Fe(2+) and H(2)O(2), which is approximately 11; however, for
      leachate treatment, a median optimum relative dose of 1.8 (w/w) (3.0M/M) was
      observed. Biologically treated leachate showed relatively lower optimum ratio of
      H(2)O(2)/Fe(2+) doses (median: 0.9 w/w) as compared to raw (median: 2.4 w/w) and
      coagulation treated (median: 2.8 w/w) leachate. Median absolute doses of H(2)O(2)
      and Fe(2+) were 1.2mg H(2)O(2)/mg of initial COD (COD(0)) and 0.9 mg Fe(2+)/mg
      COD(0), respectively and raw leachate required higher reagent doses compared to
      pretreated leachates. A universal Fenton oxidation relationship between COD
      removal efficiency (eta) and COD loading factor (L(COD)) for landfill leachate
      treatment was developed. As L(COD) increases from 0.03 to 72.0, eta varies
      linearly as eta=0.733 L(COD)-0.182. This robust linear relationship between
      L(COD) and eta holds for Fenton oxidation of raw as well as biological and
      coagulation treated leachates. The relationship was validated using Leave-one-out
      cross validation technique and errors in predicting eta using L(COD) were
      evaluated by applying Monte Carlo Simulation. As a result, the relationship can
      be used as a universal equation to predict Fenton treatment efficiency for a
      given COD(0) loading in the range of 0.03-72.0 for landfill leachate treatment.

PMID- 22980911
TI  - Anti-reflux procedure for difficult-to-treat asthmatic children, case report and
      literature review.
AB  - Gastroesophageal reflux disease (GERD) is a commonly encountered condition in
      children, which at times causes respiratory distress, such as asthmatic symptoms,
      and results in serious morbidity and even mortality. The complexity is sometimes
      so obscure, that it can cause paradoxical diagnoses and treatment. Here we
      present two cases of children with difficult-to-treat asthmatic symptoms, which
      were eventually found to be related to GERD. The two children were treated with
      anti-reflux procedures and both became symptom free. Literature was also reviewed
      to shed a light into this complex disease.

PMID- 22980912
TI  - Detection of swing heel-off event in gait initiation using force-plate data.
AB  - This study investigated the accuracy and reliability of four methods using force
      plate data for detecting the swing heel-off (HO) time in gait initiation. Results
      of these methods were compared to those obtained by means of a reference method
      using a footswitch. Ten young healthy adults performed 18 forward gait initiation
      trials at self-selected speed and at maximal speed. Results showed that the
      method based on vertical impulse was the most accurate and reliable in
      determining HO in both speed conditions. The mean error obtained with this method
      was -8+/-10ms in the self-selected speed condition (-7+/-10ms in the maximal
      speed condition), with no significant effect of gait speed (P>0.05). These
      findings suggest that this method based on force-plate data is valid and reliable
      for detecting HO in forward gait initiation in the absence of additional
      hardware.

PMID- 22980913
TI  - The isolation and characterization of Campylobacter jejuni bacteriophages from
      free range and indoor poultry.
AB  - Six hundred and sixty one samples - primarily fresh chicken faeces - were
      processed to isolate wild type Campylobacter jejuni bacteriophages, via overlay
      agar methods using C. jejuni NCTC 12662. The aims of this study were to isolate
      and purify bacteriophages and then test for their ability to lyse field strains
      of C. jejuni in vitro. Of all samples processed, 130 were positive for
      bacteriophages. A distinct difference was observed between samples from different
      poultry enterprises. No bacteriophages could be isolated from indoor broilers.
      The majority of bacteriophages were isolated from free range poultry - both
      broilers and egg layers. Bacteriophages were purified and then selected for
      characterization based on their ability to produce clear lysis on plaque assay,
      as opposed to turbid plaques. Two hundred and forty one C. jejuni field isolates
      were tested for sensitivity to the bacteriophages. Lysis was graded subjectively
      and any minimal lysis was excluded. Using this system, 59.0% of the C. jejuni
      isolates showed significant sensitivity to at least one bacteriophage. The
      sensitivity to individual bacteriophages ranged from 10.0% to 32.5% of the C.
      jejuni isolates. Five bacteriophages were examined by electron microscopy and
      determined to belong to the Myoviridae family. The physical size, predicted
      genetic composition and genome size of the bacteriophages correlated well with
      other reported Campylobacter bacteriophages. The reasons for the observed
      difference between indoor broilers and free range poultry is unknown, but are
      postulated to be due to differences in the Campylobacter population in birds
      under different rearing conditions.

PMID- 22980914
TI  - Clinically significant anti M antibodies--a report of two cases.
AB  - INTRODUCTION: Most anti-M antibodies are not active at 37 degrees C and are thus
      of no clinical significance. Occasionally these antibodies have a wide thermal
      range and can lead to hemolytic transfusion reactions or hemolytic disease of the
      new born. PATIENT AND METHODS: We describe two cases of anti-M antibodies, both
      of which were clinically significant. RESULTS: The first case was detected due to
      crossmatch incompatibility and the second presented as a blood group discrepancy.
      CONCLUSION: When the antibody is active at 37 degrees C, M antigen negative red
      cell units should be issued.

PMID- 22980915
TI  - Frequency of red cell alloimmunization in patients with sickle cell anemia in an
      Egyptian referral hospital.
AB  - INTRODUCTION: Sickle cell anemia (SCA) is an important public health issue in
      Tanta, Egypt. Erythrocyte transfusions may reduce the morbidity of SCA, however,
      they are associated with numerous risks. Among other risk categories,
      alloimmunization to red cell antigens may result from transfusions. The objective
      of this study was to explore the frequency of red cell alloantibodies among SCA
      patients who received regular transfusions. MATERIALS AND METHODS: A total of 42
      patients with SCA were included in this study. This work planned to study the
      presence of alloantibodies to different red cell antigens in multi-transfused SCA
      patients using the ID card micro-typing system. Clinical and laboratory data were
      collected and analyzed to find out the frequency, pattern and factors influencing
      red cell alloimmunization secondary to multiple blood transfusion in these
      patients. RESULTS: Of a total of 42 SCA patients included in the study, 21.4% of
      patients developed alloantibodies. The most common alloantibodies were anti-K,
      anti-E and anti-C. The rate of incidence of these alloantibodies was 7.1%, 4.8%
      and 4.8%, respectively. There was significant association between alloantibody
      and the rate of transfused blood. The mean age of patients with and without
      alloimmunization was 12.0 and 6.2 years. CONCLUSIONS: Alloimmunization to minor
      erythrocyte antigens of variable clinical significance is a frequent finding in
      transfused SCA patients. Regular screening for red cell alloantibodies would
      provide better management of these patients.

PMID- 22980916
TI  - Fatal delayed hemolytic transfusion reaction associated with anti-Di(b) and anti
      E.
AB  - We report the death of a 61-year-old Japanese man massively transfused during and
      after emergency aortic surgery. Postoperative on day 8, he died after cardiac
      arrest associated with hyperkalemia. Indirect antiglobulin testing demonstrated
      both anti-Di(b) and anti-E antibodies pre-transfusion, and elevation of their
      titers as the delayed hemolytic transfusion reaction evolved. Monocyte monolayer
      assay (induction of reactive monocytes) and flow cytometry (increase of IgG1
      and/or IgG3) gave evidence of the clinical significance of both antibodies. Anti
      Di(b) must be considered when an antibody to a high incidence antigen is found in
      Japanese and other Mongoloid populations.

PMID- 22980917
TI  - Serological characteristic and molecular basis of A2 subgroup in the Chinese
      population.
AB  - BACKGROUND: A2 phenotype is a common subgroup of blood group A, but the
      serological characteristic and genetics basis of A2 phenotype currently was rare
      reported in the Chinese Han population. Here, a large scale study of the serology
      and genetics of A2 and A2B phenotypes was performed. METHODS/MATERIALS: 11263
      Chinese individuals with group A and AB phenotypes were determined for A2 antigen
      with the standard serological method. The full coding region of the ABO gene was
      sequenced in the individuals with A2 and A2B phenotypes. Some samples including
      each ABO genotypes were chosen for determining the activity of
      glycosyltransferase A (GTA) in plasma. RESULTS: 134 individuals were assigned as
      A2 and A2B phenotypes in 11263 individuals. There was imbalance in A2 and A2B
      phenotypes and the proportion of A2B among AB samples was significantly higher
      than that of A2 in group A samples. All samples of the A2 and A2B phenotypes were
      classified into A2-related allele group, A1-related allele group and the other
      group based on kind of the ABO genotype. Four novel A2-related alleles (A217,
      A218, A219, A220) were identified. The individuals with same genotype showed
      different agglutination strength with anti-A1 and anti-H on their RBCs. The
      plasma from individuals with A2-related allele had almost no GTA activity, while
      plasma from individuals with A1-related allele had some GTA activity. CONCLUSION:
      A2 and A2B phenotypes could derive from different genotypes and the serological
      characteristic may be heterogeneity in the Chinese Han population.

PMID- 22980918
TI  - Sex differences in language asymmetry are age-dependent and small: a large-scale,
      consonant-vowel dichotic listening study with behavioral and fMRI data.
AB  - Men are often believed to have a functionally more asymmetrical brain
      organization than women, but the empirical evidence for sex differences in
      lateralization is unclear to date. Over the years we have collected data from a
      vast number of participants using the same consonant-vowel dichotic listening
      task, a reliable marker for language lateralization. One dataset comprised
      behavioral data from 1782 participants (885 females, 125 non-right-handers), who
      were divided in four age groups (children <10 yrs, adolescents = 10-15 yrs,
      younger adults = 16-49 yrs, and older adults >50 yrs). In addition, we had
      behavioral and functional imaging (fMRI) data from another 104 younger adults (49
      females, aged 18-45 yrs), who completed the same dichotic listening task in a 3T
      scanner. This database allowed us to comprehensively test whether there is a sex
      difference in functional language lateralization. Across all participants and in
      both datasets a right ear advantage (REA) emerged, reflecting left-hemispheric
      language lateralization. Accordingly, the fMRI data revealed a leftward asymmetry
      in superior temporal lobe language processing areas. In the N = 1782 dataset no
      main effect of sex but a significant sex by age interaction emerged: the REA
      increased with age in both sexes but as a result of an earlier onset in females
      the REA was stronger in female than male adolescents. In turn, male younger
      adults showed greater asymmetry than female younger adults (accounting for <1% of
      variance). There were no sex differences in children and older adults. The males
      in the fMRI dataset (N = 104) also had a greater REA than females (accounting for
      4% of variance), but no sex difference emerged in the neuroimaging data.
      Handedness did not affect these findings. Taken together, our findings suggest
      that sex differences in language lateralization as assessed with dichotic
      listening exist, but they are (a) not necessarily reflected in fMRI data, (b) age
      dependent and (c) relatively small.

PMID- 22980919
TI  - Protein anticoagulants targeting factor VIIa-tissue factor complex: a
      comprehensive review.
AB  - Anticoagulants are pivotal for the treatment of debilitating thromboembolic and
      associated disorders. Current anticoagulants such as heparin and warfarin are non
      specific and have a narrow therapeutic window. These limitations have provided
      the impetus to develop new anticoagulant therapies/strategies  that target
      specific factors in the blood coagulation cascade, ideally those located upstream
      in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it,
      in complex with tissue factor (TF), acts as the prima ballerina for the formation
      of blood clot. A comprehensive review  delineating the structure-activity
      relationship of protein/peptide anticoagulants targeting FVIIa or TF-FVIIa
      complex is absent in the literature. In this article, we have addressed this
      deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF
      FVIIa  complex. Further, the current status of these anticoagulants, with regard
      to their performance in different clinical trials has also been presented.
      Lastly, the unexplored domains of these unique proteins have also been
      highlighted, which will facilitate further translational research in this 
      paradigm, to improve strategies to counter and treat thromboembolic disorders.

PMID- 22980920
TI  - The interplay of conflict and analogy in multidisciplinary teams.
AB  - Creative teamwork in multidisciplinary teams is a topic of interest to cognitive
      psychologists on the one hand, and to both social and organizational
      psychologists on the other. However, the interconnections between cognitive and
      social layers have been rarely explored. Drawing on mental models and dissonance
      theories, the current study takes a central variable studied by cognitive
      psychologists-analogy-and examines its relationship to a central variable
      examined by social psychologists-conflict. In an observational, field study, over
      11h of audio-video data from conversations of the Mars Exploration Rover
      scientists were coded for different types of analogy and micro-conflicts that
      reveal the character of underlying psychological mechanisms. Two different types
      of time-lagged logistic models applied to these data revealed asymmetric patterns
      of associations between analogy and conflict. Within-domain analogies, but not
      within-discipline or outside-discipline analogies, preceded science and work
      process conflicts, suggesting that in multidisciplinary teams, representational
      gaps in very close domains will be more likely to spark conflict. But analogies
      also occurred in reaction to conflict: Process and negative conflicts, but not
      task conflicts, preceded within-discipline analogies, but not to within-domain or
      outside-discipline analogies. This study demonstrates ways in which cognition can
      be bidirectionally tied to social processes and discourse.

PMID- 22980921
TI  - Biotechnologies for the management of genetic resources for food and agriculture.
AB  - In recent years, the land area under agriculture has declined as also has the
      rate of growth in agricultural productivity while the demand for food continues
      to escalate. The world population now stands at 7 billion and is expected to
      reach 9 billion in 2045. A broad range of agricultural genetic diversity needs to
      be available and utilized in order to feed this growing population. Climate
      change is an added threat to biodiversity that will significantly impact genetic
      resources for food and agriculture (GRFA) and food production. There is no
      simple, all-encompassing solution to the challenges of increasing productivity
      while conserving genetic diversity. Sustainable management of GRFA requires a
      multipronged approach, and as outlined in the paper, biotechnologies can provide
      powerful tools for the management of GRFA. These tools vary in complexity from
      those that are relatively simple to those that are more sophisticated. Further,
      advances in biotechnologies are occurring at a rapid pace and provide novel
      opportunities for more effective and efficient management of GRFA. Biotechnology
      applications must be integrated with ongoing conventional breeding and
      development programs in order to succeed. Additionally, the generation,
      adaptation, and adoption of biotechnologies require a consistent level of
      financial and human resources and appropriate policies need to be in place. These
      issues were also recognized by Member States at the FAO international technical
      conference on Agricultural Biotechnologies for Developing Countries (ABDC-10),
      which took place in March 2010 in Mexico. At the end of the conference, the
      Member States reached a number of key conclusions, agreeing, inter alia, that
      developing countries should significantly increase sustained investments in
      capacity building and the development and use of biotechnologies to maintain the
      natural resource base; that effective and enabling national biotechnology
      policies and science-based regulatory frameworks can facilitate the development
      and appropriate use of biotechnologies in developing countries; and that FAO and
      other relevant international organizations and donors should significantly
      increase their efforts to support the strengthening of national capacities in the
      development and appropriate use of pro-poor agricultural biotechnologies.

PMID- 22980922
TI  - Transposable elements and insecticide resistance.
AB  - Transposable elements (TEs) are mobile DNA sequences that are able to copy
      themselves within a host genome. They were initially characterized as selfish
      genes because of documented or presumed costs to host fitness, but it has become
      increasingly clear that not all TEs reduce host fitness. A good example of TEs
      benefiting hosts is seen with insecticide resistance, where in a number of cases,
      TE insertions near specific genes confer resistance to these man-made products.
      This is particularly true of Accord and associated TEs in Drosophila melanogaster
      and Doc insertions in Drosophila simulans. The first of these insertions also has
      sexually antagonistic fitness effects in the absence of insecticides, and
      although the magnitude of this effect depends on the genetic background in which
      Accord finds itself, this represents an excellent example of intralocus sexual
      conflict where the precise allele involved is well characterized. We discuss this
      finding and the role of TEs in insecticide resistance. We also highlight areas
      for further research, including the need for surveys of the prevalence and
      fitness consequences of the Doc insertion and how Drosophila can be used as
      models to investigate resistance in pest species.

PMID- 22980923
TI  - Implementing clinical supervision for Australian rural nurses.
AB  - In a practice environment characterised by diversity and unpredictability, the
      role of rural nurses is described as challenging. Developing strategies to
      support rural nurses is important, for recruitment and retention, and to ensure
      that nurses provide quality services for rural communities. Most researchers
      recommend ongoing education as almost a panacea to the challenges that rural
      nurses face. In this Australian study, there was interest in exploring the
      potential for clinical supervision as a mechanism for supporting rural nurses.
      Clinical supervision has been identified as a useful means of reflecting on
      practice, building resilience, reducing stress and avoiding burnout. A six month
      clinical supervision programme was developed and implemented with twenty two
      rural nurses. Using an interpretive descriptive design, a group discussion on
      participant views of the programme was conducted. Using a thematic network
      approach, three themes; becoming reflective, understanding and commitment, and
      losing the client were developed. While in no way devaluing the usefulness of
      clinical supervision, the findings from this study provide guidance for others
      introducing similar programmes and indicate that clinical supervision must be
      focused, well planned and supported.

PMID- 22980924
TI  - Novel deletion mutation in the cardiac sodium channel inactivation gate causes
      long QT syndrome.

PMID- 22980925
TI  - Evaluation of short-term changes in body fluid status by a novel method using a
      commercially available body-fat analyzer: observations from maintenance
      hemodialysis patients.

PMID- 22980926
TI  - The future of integrase inhibitors of HIV-1.
AB  - Integration of the HIV-1 DNA is required and essential to maintain the viral DNA
      in the infected cell. Integration process occurs in several events, mainly
      endonucleolytic processing of the 3' ends of the viral DNA and strand transfer or
      joining of the viral and cellular DNA. The design and discovery of integrase
      inhibitors were first focused at targeting the catalytic site of IN with a
      specific effect on strand transfer. Several integrase inhibitors were developed
      clinically, two first generation inhibitors, raltegravir and elvitegravir and
      then two second-generation inhibitors, dolutegravir and MK-2058. Recently,
      allosteric integrase inhibitors intended to interfere with the integrase
      LEDGF/p75 interaction have been designed. These new inhibitors called LEDGINs
      have an effect on 3' processing and strand transfer. Thus, integrase inhibitors
      present a real added value in combined treatment for naive and experienced HIV
      infected patients. Combination experiments of LEDGINs and raltegravir suggest
      that these inhibitors could act additively despite sharing the same viral target.
      Future therapy could involve combinations of inhibitors of IN function acting
      though different binding pockets within IN. The place of this class on HIV
      inhibitors and their future role in perspective of novel therapies to eliminate
      latent HIV reservoirs and infection for cure should also be explored.

PMID- 22980927
TI  - Periprosthetic fractures around the knee: update on therapeutic algorithms for
      internal fixation and revision arthroplasty.
AB  - Effective treatment of periprosthetic fractures following TKA continues to
      represent a surgical challenge. The incidence and frequency of these complicated
      type of fractures is expected to increase as the number of TKA as well as the
      activity level of these patients steadily rises. A careful and correct analysis
      of the fracture pattern, its classification, the quality of the existing bone
      stock and the fixation / loosening of the underlying prosthetic system has to
      precede decision making for successful conservative or surgical treatment.
      Therefore, improved diagnostic radiographic imaging of fracture patterns and
      reliable assessment of prosthesis loosening progressive development of new
      implant methods and refinement of soft tissue preserving surgical techniques will
      hold the key for regaining the functional level prior to the fracture.

PMID- 22980928
TI  - Treatment of proximal humeral fractures - a review of current concepts
      enlightened by basic principles.
AB  - Fractures of the proximal humerus commonly affect elderly patients. The vast
      majority of proximal humeral fractures result from low-energy trauma in presence
      of osteoporosis. Incidence of proximal humeral fractures dramatically increased
      over the last decades. Recent epidemiological studies expect a rather stagnant
      incidence. Diversity of fracture types attenuates reliability of available
      classification systems. Even though, predictive morphologic criteria have been
      detected enabling a prognostic assessment. A short or absent metaphyseal head
      extension and disruption of the medial periosteal hinge reliably predict ischemia
      of the humeral head fragment. Still, humeral head necrosis may be prevented in
      early reduction and fixation. The range of treatment options consists of non
      operative therapy, minimal-invasive osteosynthesis, open reduction and plate
      fixation, intramedullary nailing and primary arthroplasty. Most proximal humeral
      fractures in the elderly are stable injuries and can be successfully treated by
      non-operative means. Operative treatment of displaced, unstable fractures should
      resort to the least invasive procedure providing adequate reduction and fixation
      stability. To date, open reduction and locking plate osteosynthesis represents
      the standard operative procedure in displaced three- and four-part fractures.
      However, a number of risk factors may promote fixation failure or impair
      functional outcome, most important low local bone mineral density, residual varus
      displacement of the humeral head, insufficient restoration of medial calcar
      support, humeral head ischemia and insufficient fracture reduction. Innovation of
      fixation techniques (e. g. angular stable locking systems and bone augmentation)
      will further expand indications for operative fracture treatment. Outcome of
      hemiarthroplasty is closely related to anatomical tuberosity healing and
      restoration of rotator cuff function. Reverse shoulder arthroplasty may provide
      satisfactory shoulder function in geriatric patients, rotator cuff dysfunction or
      failure of first-line treatment. Choice of treatment should be individualized and
      base on careful evaluation of patient-specific, fracture-specific and surgeon
      specific aspects.

PMID- 22980929
TI  - [Cementless Plasmacup-Bicontact total hip arthroplasty. Results of a minimum of
      ten-year follow-up].
AB  - PURPOSE OF THE STUDY: The aim of the study was to analyse the long-term clinical
      and radiographic results of total hip arthroplasty (THA) with the Bicontact
      Plasmacup prosthesis, MATERIAL AND METHODS: In this retrospective observational
      study, 34 consecutive patients undergoing Bicontact-Plasmacup THA between August
      1998 and July 2000 were evaluated. The group included 15 women and 19 men with an
      average age of 56 years (30 to 67 years). The mean +/- SD of follow-up was 132 +/
      9 months (122 to 149 months). Patients' satisfaction with the treatment outcome
      and selected clinical and radiographic features were evaluated. The data were
      analysed using the concordance test, Spearman's correlation coefficient and chi
      square test. RESULTS: At the final follow-up, 94% of the interviewed patients
      reported satisfaction with the surgery outcome. The mean Harris score was 93 (67
      to 98) points, with excellent or very good results in 91% of the patients.
      Compared with the post-operative radiographs, the mean +/- SD value for vertical
      migration of the acetabular cup was 2.43 +/- 3.21 mm (0 to 12 mm) and that for
      horizontal migration was 0.35 +/- 1.0 mm (0 to 4.3 mm). The mean stem subsidence
      was by 3.87 mm (range, 0.36 to 21.11 mm; SD 4.03). At the final follow-up, all
      implants showed radiographic stability and absence of radiolucent lines. Early
      acetabular osteolysis was detected in two patients (5.9 %). In 19 patients (56%)
      a change in bone architecture, similar to alterations due to weight-bearing
      adaptation, was seen around the cup following surgery. The stress shielding
      effect of the femoral component was recorded in 79%, bypass phenomenon in 41 %
      and pedestal formation under the apex of the stem in 18% of the patients. The
      mean rate of polyethylene wear measured by the Dorr and Wan method was 0.106 mm
      per year (range, 0.00 to 0.267 mm) or it was 0.078 mm per year (0.00 to 0.19 mm)
      when assessed by a modification of the method described by Kang et al.
      DISCUSSION: The clinical and radiographic findings presented here are in
      accordance with the relevant literature data. This implant design is associated
      with a relatively infrequent osteolysis around the cup probably due to a low wear
      rate of polyethylene and a stable polyethylene liner-metal cup interface. Based
      on this work and some other studies it can be concluded that a post-operative
      migration of several millimetres is compatible with a long-term, stable
      cementless THA. CONCLUSIONS: The Bicontact-Plasmacup THA meets the National
      Institute for Health and Clinical Excellence (NICE) criteria for a very good
      implant (ten-year survival rate of over 90%). At 10 years after surgery, however,
      the first signs of complaints about surgery outcome // dissatisfaction with
      surgery outcomes were recorded. This may, at least partly, be related to aseptic
      loosening which is one of the symptoms of particle disease.

PMID- 22980930
TI  - [Comparison and statistical evaluation of two methods of condylar twist angle
      measurement in total knee arthroplasty].
AB  - PURPOSE OF THE STUDY: The aim of this prospective randomised study was to compare
      and statistically analyse two methods of condylar twist angle (CTA) measurement
      in total knee arthroplasty in order to assess their applicability in routine
      practice. MATERIAL AND METHODS: The study included 238 patients with 256 sites
      undergoing total knee arthroplasty (TKA) in the period from January 2009 to May
      2011. There were 93 men (nine with bilateral TKA) and 145 women (nine with
      bilateral TKA) with an average age of 69.3 years and a range of 47 to 88 years.
      The implants NexGen (Zimmer) and ADVANCE(r) Medial-Pivot Knee (Wright) were used.
      In each patient, CTA was measured before surgery by the radiologist on a
      multidetector CT SOMATOM 64 (Siemens) using the Yoshioki method. The other CTA
      measurement was made intra-operatively by the surgeon using our modification of
      the Hofmann method which involved the identification of a reference line for
      optimal rotational alignment of the femoral component. A STATISTICA 9.0 software
      package was used for statistical analysis. In addition to basic statistical data,
      selected data were presented in graphical forms as Box and Whisker's plots and
      histograms. Changes in CTA and differences between the groups were evaluated
      using the Wilcoxon signed-rank test. Relationships among the variables were
      studied using Spearman's correlation coefficient. RESULTS: The statistical
      analysis showed that the pre-operative CTA value obtained from CT scans was, on
      the average, higher by 0.5 degrees than the value from intra-operative
      measurement, as assessed at the level of significance p = 0.001 (signed- rank
      test). The intra-individual variability was lower than the inter-individual one
      (14.4% and 30.8%, respectively). This means that both methods are suitable for
      CTA measurement in the knee joint replacement procedures. Spearman's correlation
      coefficient was 0.6, which is the value of medium strong correlation. The post
      operative CTA assessed on CT scans was in the range of 0 to 2 degrees in 87.5% of
      the patients. Both the pre-operative and intra-operative CTA values were
      significantly higher in women than in men (Wilcoxon two-sample test). There was
      no statistical difference between the left and the right side. DISCUSSION:
      Malrotation of the femoral component is one of the causes leading to patellar
      subluxation and pain in the front part of the knee. The post-operative CTA value
      should be zero. Optimal rotational alignment of the femoral component varies with
      each patient; in our study it was found in the range of 0 to 7 degrees on the
      basis of CTA values. We do not recommend 7 degrees of external rotation to be
      exceeded because of the risk associated with balancing the flexion gaps; nor do
      we recommend to set internal rotation of the femoral component for the risk of
      patellar complications. The difference of 0.5 degree found in the CTA value
      between the two measuring methods can be explained by individual differences in
      the anatomy of the medial epicondylar region, and by the use of only selected
      whole numbers (0, 3, 5, 7) in intra-operative measurements. This difference does
      not play any role in routine surgical procedures. CONCLUSIONS: The statistical
      evaluation of the results of CTA measurement with the two methods showed that
      both were equally suitable for routine total knee arthroplasty. The results of
      intra-operative CTA measurements are comparable with those obtained on CT scans;
      in addition, the intra-operative method is less expensive and eliminates exposure
      of the patient to radiation. CT-based CTA measurements are useful in the patients
      with chronic problems after TKA in whom femoral component malrotation needs to be
      either confirmed or ruled out.

PMID- 22980931
TI  - Computer-assisted navigation in total knee arthroplasty without femoral hardware
      removal.
AB  - PURPOSE OF THE STUDY: The use of navigation applied to total knee arthroplasty in
      knees with femoral hardware retained has not been studied. MATERIAL AND METHODS:
      We use navigation in six patients to implant a total knee arthroplasty while
      retaining the femoral hardware. The retained materials were screws in two cases,
      diaphyseal plates in another two, intramedullary nails in one and supracondylar
      tube/plate in another one. Preoperative knee scores were within the 46-66 range,
      whereas the functional scores were within 40-68. The coronal deformity varied
      between 30 degrees  varus and 5 degrees  valgus. RESULTS: The final femoral
      mechanical axis was between 2 degrees  valgus and 3 degrees  varus; the axis of
      the limb was between 4 degrees  valgus and 3 degrees  varus. Knee scores improved
      in all cases, with scores between 75 and 90 points (p = 0.028); functional scores
      were between 64 and 90 points (p = 0.043).The final range of mobility was within
      the 70 degrees -110 degrees  range, with a slight improvement over the
      preoperative status (p = 0.042). No complications have arisen throughout the
      follow-up (mean 16 months). CONCLUSIONS: The use of navigation constitutes a good
      option in the treatment with total arthroplasties for patients with femoral
      hardware retained.

PMID- 22980932
TI  - [Minimally invasive fixation of the pelvic ring with a transiliacal internal
      fixator].
AB  - PURPOSE OF THE STUDY: To evaluate the results of stabilisation of the posterior
      pelvic segment with a transiliacal internal fixator (TIFI) in type C fractures of
      the pelvis. MATERIAL AND METHODS: Between 2008 and 2011, the TIFI method was used
      in 27 patients with unstable type C pelvic ring fractures (AO classification) at
      our department. The patient group included 15 men and 12 women with an average
      age of 35 years (range, 15 to 65 years). All patients suffered high-energy trauma
      in traffic accidents (59.3%), by falls from a height (33.3%) or due to other
      causes (7.4%). In 40.7% of the patients, pelvic injury was part of polytrauma.
      Fixation was carried out using two polyaxial screws and the rod of a spinal
      instrumentation Legacy(r) or Colorado(r). The method was employed for unilateral
      SI joint dislocation in five cases, and for unilateral sacral fractures of
      Pohlemann type I in six cases, Pohlemann type II in 13 cases and Pohlemann type
      III in three cases. The patients were mobilised, with associated injuries taken
      into consideration, at 5 post-operative weeks on the average. They were followed
      up at 6-week intervals until healing of fracture, then at one year after surgery
      and every 12 months thereafter. RESULTS All 27 patients achieved bone union
      within 6 months. The average operative time was 29 min (21 to 45 min). The
      average hospital stay was 22 days (11 to 66 days). The average duration of bed
      rest was 36 days (14 to 71 days). Complications included bronchopneumonia in two
      patients, and a redislocation with displacement of the posterior segment up to 10
      mm in one patient. DISCUSSION: Transiliacal internal fixation is a minimally
      invasive method used to treat unstable pelvic ring fractures. Compared to other
      types of fixation, it carries a low risk of injury to nerve and vascular
      structures as well as a low risk of infectious complications, is associated with
      low blood loss and is easy to perform. The TIFI provides stability comparable
      with the use of two iliosacral screws, without the risk of excessive compression
      even in comminuted transforaminal fractures of the sacrum. However, the need to
      operate on patients lying in the prone position is a disadvantage because, in
      polytraumatised patients, it makes implantation at the acute phase impossible.
      CONCLUSIONS: The TIFI technique is one of the options for fixation of posterior
      pelvic segment fractures. A short operative time and minimum complications are
      undeniable advantages. Indications should be carefully considered in each
      patient. TIFI is a minimally invasive method for anterior pelvic segment fixation
      that can also be used in the acute stage of injury.

PMID- 22980933
TI  - [Treatment of humeral shaft fractures using Hackethal's technique of
      intramedullary bundle nailing].
AB  - PURPOSE OF THE STUDY To inform on our experience with the treatment of humeral
      shaft fractures by intramedullary osteosynthesis using Hackethal's bundle nailing
      and to evaluate indications for the current use of this technique. MATERIAL AND
      METHODS From January 2001 to December 2009, a total of 184 patients with humeral
      shaft fractures were treated surgically and, of these, 147 by Hackethal's
      nailing. From January 2006 60 patients treated by this technique were
      prospectively followed up and, of them, 50 were evaluated (83.3%) and included in
      this study. The average age of the study group was 51.2 years. Fifteen fractures
      (30%) were in the proximal third, 32 (64%) in the middle third and three (6%) in
      the distal third of the humeral diaphysis. According to the AO classification,
      the distal-third diaphyseal fractures were mostly type A2 (26.6%) and type B1
      (20.1%) , mid-third fractures were mostly type A3 (31.3%) and distal-third
      fractures were not evaluated because of their low number. Based on radiographic
      examination, patients with uncomplicated fractures of the humeral shaft were
      indicated for surgery. This was performed according to the original Hackethal's
      procedure with the patient in the prone position using Kirschner wires, 2 mm in
      diameter, as implants. The patients were followed up at 6 weeks and 3, 6, 9 and
      12 months after surgery. On examination, healing of the operative wound, bony
      union achieved and radiographic findings of the fragment position were evaluated.
      The range of mo tion at the shoulder and elbow was assessed and subjective
      patients' feelings were recorded. RESULTS Of the 50 patients evaluated, 45 (90%)
      healed by first intention, four developed pseudoarthrosis (8%) and one required
      repeat surgery. No deep wound infection was recorded. Six patients (12%) had
      humeral angulation up to 10 degrees and one (2%) up to 13 degrees. This
      angulation was recorded in proximal-third diaphyseal fractures. A deviation in
      humeral internal rotation was found in two patients (4 %), in one of whom it was
      40 degrees. Mild restriction of elbow extension (10 degrees) was found in two
      patients (4%), five (10%) reported slightly restricted motion of the shoulder and
      five, chiefly elderly patients with proximal-third diaphyseal fractures, had
      severe restriction of shoulder motion. Most of the patients (78%) reported full
      satisfaction, including return to normal daily activities, at 6 months after
      injury. When the therapy was finished at 12 months after surgery, 44 patients
      (88%) expressed their full satisfaction. DISCUSSION Our results give support to
      the previously reported good outcomes of Hackethal's osteosynthesis of the
      humeral shaft. This method is associated with a minimum of complications if the
      conditions of correct indication are fulfilled, i.e., uncomplicated fractures of
      the mid-third humeral diaphysis are considered. Filling the medullary cavity
      completely with K-wires or nails is an additional condition. Without these being
      met, good stability of the fracture is not achieved and non-union can develop, as
      shown by the analysis of cases with non-union in our patient group. CONCLUSIONS
      Hackethal's technique of osteosynthesis with elastic bundle nailing facilitates
      safe and easy treatment of uncomplicated diaphyseal fractures of the humerus. Its
      outcomes are comparable with the other currently used and more expensive methods.
      It is the method of first choice in the treatment of transverse and short oblique
      fractures of the mid-third of the humeral shaft. Key words: humeral shaft
      fractures, bundle nailing, Hackethal's technique.

PMID- 22980934
TI  - [True/Flex intramedullary nailing for forearm shaft fractures. Long-term
      results].
AB  - PURPOSE OF THE STUDY: Presentation of technical experience and the clinical and
      functional results of intramedullary fixation of forearm shaft fractures.
      MATERIAL AND METHODS: Between January 1994 and December 2009, a total of 96
      patients with 144 radial and/or ulnar fractures (ulna, 33; radius,15; both, 48)
      were treated by nailing (True/Flex(r)). According to the AO classification there
      were 22-A, 22-B and 22-C type fractures in 39 (41%), 44 (46%) and 13 (13%).cases,
      respectively. Of these, 82 (85%) were closed (types: 0, 48; I, 33; II, 1) and 14
      (15%) were open (types: I, 13; II, 1; III, 0) fractures. Seventy-eight patients
      (81%) were followed up and their functional outcomes were evaluated according to
      the criteria of Anderson et al. The average interval between the operation and
      final follow-up was 28 months (15 to 96 months) RESULTS: The average time to
      surgery was 2.2 days (0 to 25 days). Early complications were recorded in 4% of
      the patients (1x bursitis olecrani; 1x end cup replacement; 1x bending of nails)
      and late complications in 15% (5x non-union; 2x delay union; 4x bursitis
      olecrani; 1x ruptured tendon). Bone healing was achieved in 95% of the cases and
      took on average 16 weeks (7 to 34 weeks). No infection, refracture or synostosis
      occurred. Primary loss of reduction was recorded in four cases due to distraction
      in one, bent nails in two and a wrong size of the implant in one; secondary loss
      of reduction was found in three cases, with two cases of radius shortening and
      one 10 degrees malrotation. No primary malrotation was recorded, but secondary
      loss of alignment was seen in the distal part of the radius and the proximal part
      of the ulna. Functional results according to the Anderson criteria were excellent
      and good in 87% of the cases. DISCUSSION: Intramedullary mailing provides good
      stability to mid- and distal-third shaft fractures of the ulna and mid- and
      proximalthird shaft fractures of the radius, particularly in AO type A and type B
      fractures. The technical aspects of the method are analysed in detail in this
      paper. CONCLUSIONS: True/Flex(r) intramedullary nailing, because of its minimally
      invasive approach and close reduction, allows us to minimise the risk of wound
      and neurovascular complications, especially in proximal shaft fractures of the
      radius.

PMID- 22980935
TI  - [The effect of releasing the medial stabilisers of the knee on the magnitude of
      correction in opening-wedge high-tibial valgus osteotomy. Anatomy study on
      cadavers].
AB  - PURPOSE OF THE STUDY: When a larger opening of high-tibial osteotomy is necessary
      to achieve good correction of the lower extremity axis, partial release of the
      attachments of the medial stabilisers of the knee may be required. The aim of the
      study was to ascertain, in cadaver specimens, the effect of loosening the medial
      knee stabilisers on the magnitude of correction in medial opening-wedge high
      tibial valgus osteotomy. MATERIAL AND METHODS: Thirty-eight knees obtained from
      cadavers of Caucasian race were dissected. Medial opening-wedge high-tibial
      valgus osteotomy was performed using a dynamic distractor, constructed by us,
      with a dynamometer to ensure constant force action. Using a kinematic navigation
      system, the lower leg axis was studied at opening-wedge osteotomy under constant
      forces of 100 N and 150 N. The change in its angulation was recorded after each
      step in releasing the medial stabilisers whose structures were gradually made
      loose, under constant action of the given force, in the following order:
      superficial portion of the medial collateral ligament, tendons of the gracilis,
      semitendinosus and sartorius muscles. RESULTS: The results were statistically
      analysed using descriptive statistical methods and the two-sample paired t-test
      with the level of statistical significance set at p < 0.05. Loosening of the
      medial stabilisers one by one under a constant load led to a statistically
      significant change in alignment. The most significant change in angulation, both
      in clinical and statistical terms, was that of 3.4 degrees  occurring after the
      superficial portion of the medial collateral ligament was made loose under a
      constant force of 100 N applied to osteotomy. Thus, this loosening contributed by
      62% to an overall change of 5.5 degrees  in the lower extremity mechanical axis,
      as compared with the condition not allowing for loosening of the stabilisers.
      Under a load of 150 N applied to osteotomy, loosening of the medial collateral
      ligament resulted in a change by 4.1 degrees , which accounted for 56% of an
      overall change of 7.3 degrees  that occurred after all stabilisers were released.
      On distraction of the osteotomy using a higher force, an increase in a
      stabilising effect of the pes anserinus was apparent. DISCUSSION: The evolution
      of angle-stable implants has advanced options for reliable fixation of high
      tibial corrective osteotomy which involves cutting out a wedge and forcing it
      open on the medial side. These implants provide stable fixation even when a large
      correction of the limb mechanical axis is required, and allow for rehabilitation
      with early weight-bearing. As with a large correction the force needed to make
      the wedge open is increasing, it is necessary to consider loosening of the medial
      stabilisers of the knee. According to our knowledge, no study on the effect of
      individual medial stabilising structures of the knee on the force required to
      open high-tibial osteotomy with the wedge opened medially has been published.
      CONCLUSIONS: The process of correcting lower extremity alignment by high-tibial
      opening-wedge valgus osteotomy brings about an increase in tension of the
      stabilisers on the concave side of the deformity. Our results show an important
      role of releasing the superficial portion of the medial collateral ligament in
      the reduction of forces necessary to correct a deformity.

PMID- 22980936
TI  - [Post-operative retransfusion and intra-operative autotransfusion systems in
      total knee arthroplasty. A comparison of their efficacy].
AB  - PURPOSE OF THE STUDY: The aim of the study was to compare the effect of post
      operative retransfusion with that of intra-operative autotransfusion in non
      anaemic patients undergoing total knee arthroplasty (TKA). MATERIAL AND METHODS:
      Between February 2004 and June 2006, a total of 129 patients free of anaemia who
      underwent elective primary unilateral cemented TKA for primary arthritis received
      blood retransfusion by means of the post-operative retransfusion system. Intra
      operative transfusion was not administered. Patients with coagulation disorders,
      thrombocytopaenia or other haematological diseases were not included. The results
      were compared with those of the group of 142 patients undergoing the same
      surgery, but with use of the intra-operative autotransfusion system, in the
      period from February 2009 to December 2010. The following patient data were
      reviewed: patient's age at the time of surgery; value of haemoglobin before and
      two days after surgery; allergic and febrile reactions associated with
      retransfusion, renal failure after retransfusion, number of postoperative
      allogeneic transfusions, early TKA infection and thrombo-embolic complications.
      RESULTS: Of the 129 patients with post-operative retransfusion, 25 received one
      or more allogeneic blood transfusions due to the haemoglobin level below 90g/l
      and symptoms of anaemia. The average haemoglobin level was 136 g/l (range, 111 to
      159 g/l) one day before surgery and 107 g/l (range, 81 to 143 g/l) on the 2nd
      post-operative day. A single allogeneic blood transfusion was administered to 12
      patients and two were necessary in 13 patients. The average blood volume returned
      to the patient through the post-operative retransfusion system was 725.3 ml
      (range, 250 to 1 300 ml). Of the 142 patients with intra-operative
      autotransfusion, 11 patients required blood transfusion in the post-operative
      period, with seven receiving one and four receiving two transfusions. The average
      haemoglobin level was 135 g/l (range, 110 to 161 g/l ) one day before surgery and
      107 g/l (range, 85 to 130 g/l ) two days after it. The average volume of
      erythrocyte mass returned to the patient through the intra-operative
      autotransfusion system was 330.7 ml (range, 0 to 850 ml). No allergic, pyretic or
      other reaction or complication was recorded in either group. No early TKA
      infection occurred. DISCUSSION: No reports comparing the efficacies of post
      operative retransfusion and intra-operative auto-transfusion systems in patients
      undergoing total knee replacement have been found in the literature. Therefore,
      the only possible comparison can be made with the studies that involve patients
      receiving blood recuperation and control groups with no blood recuperation. In
      our study, 19.3% of the patients with post-operative retransfusion required
      allogeneic blood transfusion while this was necessary in only 7.7% of the
      patients with intra-operative autotransfusion. This difference was caused by a
      better efficiency of the intra-operative autotransfusion system which can treat
      up to 2 litres of harvested blood per hour and return it to the patient in the
      form of erythrocyte mass, while the post-operative retransfusion system can
      salvage only 1500 ml of blood. CONCLUSIONS: The use of either of these systems
      has proved to be a simple and safe method of reducing the need of allogeneic
      blood transfusion in the TKA procedure. While the post-operative retransfusion
      system facilitates the return of drained blood only, the more efficient "cell
      saver" technology collects blood shed during both intra- and post-operative
      periods and allows for erythrocyte mass retransfusion during and after surgery.
      Since the administration of allogeneic blood was required in less than 10% of the
      patients receiving intra-operative autotransfusion, this system was adopted as a
      more efficient method in routine TKA procedures.

PMID- 22980937
TI  - [Treatment of a ruptured extensor policis longus tendon by extensor carpi
      radialis longus transfer].
AB  - PURPOSE OF THE STUDY: Two tendons, i.e., the extensor indicis proprius (EIP) and
      the extensor carpi radialis longus (ECRL), are commonly used to reconstruct the
      function of a ruptured extensor pollicis longus (EPL) tendon. We reviewed a group
      of patients with EPL ruptures treated by ECRL tendon transfer to the EPL tendon,
      which was the method of choice. The aim was to evaluate the results and to assess
      the effect of ECRL detachment on hand function. MATERIAL AND METHODS: Twenty
      patients were treated surgically for a subcutaneous rupture of the EPL tendon
      between 2003 and 2007. Each patient was examined at 2 years after surgery. The
      range of motion (ROM) of both the injured and the contralateral hand was recorded
      and evaluated with a modified Geldmacher scoring system; a response to the DASH
      questionnaire was obtained. The mean follow-up was 24 months (19-31 months).
      RESULTS: For the ROM of the operated hand, the mean Total Active Motion (TAM) of
      98.75 degrees (60-140, SD 22.74) was calculated. The mean extension lag at the
      interphalangeal (IP) joint was 5.42 degrees (0-25, SD 8.77) and the mean IP
      flexion was 65.8 degrees (40-80, SD 13.2). In order to evaluate body side
      differences, the ROM of the contralateral thumb was recorded. The values were as
      follows: mean TAM, 141.3 degrees (115-190, SD 20.43); mean IP extension lag, 0
      degrees (0-0, SD 0); mean IP flexion, 68.8 degrees (50-80, SD 9.6). DISCUSSION:
      The extension lag at the IP joint was detected in both the operated and the
      contralateral hands. The patients examined at a longer interval after surgery
      showed an increase in extension lag. This may have been caused by undesired
      adaptation of the donor muscle, the presence of adhesions or suture loosening.
      CONCLUSIONS: The results showed increased adaptation of thumb motion to the
      extension lag at the IP joint, which had a mild effect on the patient's hand
      function. The difference in wrist extension between the operated and the
      contralateral hand corresponded to the pre-operative condition.

PMID- 22980938
TI  - [Epidemiology of critical burns in southern Moravia].
AB  - The aim of the study was to define the principal and additional characteristics
      of critical burns and to evaluate the effect of an increasing Abbreviated Burn
      Severity Index (ABSI) on mortality in burn patients admitted to the Department of
      Burns and Reconstructive Surgery, University Hospital in Brno. MATERIAL AND
      METHODS: This retrospective monocentric study included all patients older than 18
      years with critical burns involving more than 40% of the total body surface area
      (TBSA) who were admitted to the Department of Burns and Reconstructive Surgery,
      University Hospital in Brno, in the period from January 1, 2001 to December 31,
      2010. The epidemiological data evaluated included: age, gender, size of burn
      injury, mechanism of injury, required surgical intervention, mortality, length of
      hospital stay and the presence of inhalation injury. The results were
      statistically analysed. RESULTS: A total of 2 479 adult patients were admitted to
      the Department in the period under study, and 112 (4.5%) of them had critical
      burns. In this patient group, the average age was 48.7 years, the average burned
      surface area was 62.8% TBSA, and the average length of hospital stay was 37.2
      days. The male-to-female ratio was 2.39:1. Inhalation injury was diagnosed in 92
      patients (82.1%). Of the 112 patients with burn injury, 59 died (52.7%). The
      lowest mortality rate was in the age category of 31 to 40 years (21.1%) and the
      highest rate in the patients aged over 71 years. No patient with the ABSI . 8
      died while, amongst the patients with the ABSI .13, the mortality rate was 87.8%.
      DISCUSSION: No study dealing comprehensively with this topic in a patient group
      of this size has so far been published in the Czech Republic. Our results showed
      that the patients with critical burns accounted for about 5% of all patients with
      thermal trauma. The ABSI has proved to be a valuable and reliable predictor of
      survival in patients with critical burns. The extent of burned area and age were
      risk factors affecting mortality. On the other hand, the effect of inhalation
      injury on mortality, as a single risk factor, is disputable because this develops
      with an increasing burned surface area. CONCLUSIONS: The most important
      epidemiological data on patients with critical burns were evaluated. The study
      shows that although the number of patients annually admitted to hospital with
      severe burns is still high, it has nevertheless decreased recently.

PMID- 22980939
TI  - [Joint dislocation after total knee arthroplasty as an ankle fracture
      complication. Case report].
AB  - Joint dislocation after total knee arthroplasty is a rare complication. It is
      described as the result of ligamentous instability. Here we report the case of an
      82-year-old women who underwent primary total knee arthroplasty (TKA) for
      advanced primary grade III gonarthrosis. At 3 post-operative months the joint was
      stable and painless, with radiographic evidence of good TKA alignment and
      integration. At 4 months the patient suffered injury to the ankle involving a
      bimalleolar fracture and damage to knee soft tissues. The fracture was surgically
      treated. Subsequently, dorsal tibial dislocation was manifested. This was managed
      by individual intramedullary nail arthrodesis. At 8 months following the
      operation, the knee condition was satisfactory, with rigid arthrodesis and leg
      shortening of 4 cm. The patient was satisfied because she was free of pain and
      able to walk. Arthrodesis of the knee joint with an individual nail is an option
      for a definitive treatment of TKA instability. When other joints, such as ankle
      or hip joints, are injured, it is recommended to pay attention also to any TKA
      implanted previously because of potential development of instability or
      infection.

PMID- 22980940
TI  - [Fifty years of using Hackethal's osteosynthesis for humeral fractures].

PMID- 22980941
TI  - Mineralocorticoid and glucocorticoid receptor balance in control of HPA axis and
      behaviour.
AB  - An imbalance between central glucocorticoid (GR) and mineralocorticoid (MR)
      receptors is proposed to underlie the HPA axis dysregulation that associates with
      susceptibility to psychopathology (anxiety, PTSD). To test this 'balance
      hypothesis' we examined whether the impact of MR levels upon HPA-axis control and
      behaviour depended on the relative levels of GR and vice versa. Avoiding
      antenatal maternal 'programming' effects by using littermates, we generated mice
      with forebrain MR over-expression (MR(hi)) and/or simultaneous global GR under
      expression (GR(lo)). We found a significant interaction between MR and GR in
      control of the HPA-axis under stressed but not basal conditions. With reduced GR
      levels, HPA-axis activity in response to restraint stress was enhanced, likely
      due to impaired negative feedback. However, high MR in concert with reduced GR
      minimised this HPA-axis overshoot in response to stress. MR:GR balance also
      played a role in determining strategies of spatial memory during a watermaze
      probe trial: when coupled with GR under-expression, MR(hi) show enhanced
      perseveration, suggesting enhanced spatial recall or reduced exploratory
      flexibility. Other alterations in cognitive functions were specific to a single
      receptor without interaction, with both MR(hi) and GR(lo) manipulations
      independently impairing reversal learning in spatial and fear memory tasks. Thus,
      MR and GR interact in specific domains of neuroendocrine and cognitive control,
      but for other limbic-associated behaviours each receptor mediates its own
      repertoire of responses. Since modulation of HPA-axis and behavioural dysfunction
      associated with high levels of MR, selective ligands or transcriptional
      regulators may afford novel therapeutic approaches to affective
      psychopathologies.

PMID- 22980942
TI  - [If you find yourself in a hole the first thing to do is stop digging].

PMID- 22980943
TI  - [Can't see the wood for the trees].

PMID- 22980944
TI  - [Evidence-based anti-platelet treatment: PAPPS recommendations].

PMID- 22980945
TI  - [The E-Supervision of a health sciences PhD thesis].

PMID- 22980946
TI  - [Assessment of electronic medical records. Relationship between process
      indicators measured using electronic records and intermediate health outcomes in
      patients with hypertension].
AB  - OBJECTIVE: To study relationship between institutional process indicators
      (measured using electronic records) and intermediate outcomes of patients with
      hypertension. DESIGN: Cross-sectional epidemiological study. SETTING: Primary
      Care Health District 1. Madrid. 2010. PATIENTS: All patients with hypertension.
      n=80,306. MAIN MEASUREMENTS: Variables. Independent. Institutional process
      indicators. Dependent. Intermediate outcomes: blood pressure within target
      limits, LDL-cholesterol, tobacco and weight and detected complications.
      Confounding. Age, gender, co-morbidity, drugs and professional variables.
      RESULTS: The BP of 55.1% (SE 0.2%) of patients was within target limits.
      Bivariate analysis and multivariate logistic regression showed that the recording
      of some process indicators was associated with an increase in the probability to
      achieve targets in intermediate outcomes: smoking advice (OR: 1.69, 95% CI: 1.61 
      1.77), reviewing personal history (OR: 1.54, 95% CI:1.42-1.68), increase was
      less or biased: BP (OR: 1.19, 95% CI:1.14-1.25), sodium and potassium (OR: 1.14,
      95% CI:1.09-1.19), BMI (OR 1.08, 95% CI:1.04-1.12); also diabetes, edema, and
      creatinine, but there was timing bias. The relationship between other indicators
      (those oriented to lifestyle, family history, classification, urine examination,
      reviewing of drug therapy, LDL, electrocardiogram and cardiac auscultation) and a
      higher probability to achieve targets was not found. CONCLUSIONS: In
      hypertension, some institutional process indicators measured on electronic
      records were associated with an increase in the probability to achieve targets in
      intermediate outcomes. No relationship was found between other indicators. This
      suggests maintaining process and outcome measurement, to include the impact of
      interventions, to prioritize improvements in process indicators that show low
      performance and high impact and to remove or to change process indicators where
      no relationship is found.

PMID- 22980947
TI  - [Ultrasound in primary care: the Sisyphus boulder].

PMID- 22980950
TI  - Percutaneous drive-line infections into the future with the International
      Mechanically Assisted Circulatory Support (IMACS) registry.

PMID- 22980952
TI  - Two axial-flow Synergy Micro-Pumps as a biventricular assist device in an ovine
      animal model.
AB  - OBJECTIVE: This study investigated the use of 2 Synergy Micro-Pumps for full
      biventricular assist device (BiVAD) support. We examined right-sided and left
      sided hemodynamic parameters over a range of right-sided and left-sided pump
      speeds in an acute, fibrillating, non-beating-heart model in sheep. METHODS: Five
      juvenile sheep (43 +/- 2 kg) were implanted with two Synergy Micro-Pumps
      (CircuLite Inc, Saddle Brook, NJ), 1 in the right (RV) and 1 in the left
      ventricle (LV), through a median sternotomy. The RVAD outflow graft was
      anastomosed end-to-side to the pulmonary artery and the LVAD outflow to the
      ascending aorta. After surgical implantation of both pumps, ventricular
      fibrillation was induced and hemodynamic parameters were measured at 9 different
      levels of RVAD pump speed (from 20,000 to 28,000 rpm at 1,000-rpm increments),
      while the speed of the LVAD was set constant at 24,000, then at 26,000, and
      finally, at 28,000 rpm. RESULTS: At a fixed LVAD speed, RVAD and LVAD flow both
      increased identically as RVAD speed was increased. This was due to redistribution
      of blood volumes that resulted in resetting of pressure gradients across each
      pump and each vascular bed in a manner dictated by the pump pressure-flow
      characteristics. Results were similar with LVAD set at 24,000, 26,000, or 28,000
      rpm. At the highest LVAD and RVAD speeds, flow averaged 3.1 +/- 0.7 liters/min,
      and pressures in the right atrium, pulmonary artery, left atrium, and aorta
      averaged 2.2 +/- 3.7, 24.4 +/- 6.5, 22.4 +/- 5.5, and 56.6 +/- 8.5 mm Hg,
      respectively. CONCLUSION: BiVAD support with the 2 Synergy Micro-Pumps is
      feasible and able to provide full hemodynamic support in sheep. This approach
      holds promise for providing biventricular partial support in humans and, in
      particular, for full support in small adults and children.

PMID- 22980951
TI  - Complement activation is not required for obliterative airway disease induced by
      antibodies to major histocompatibility complex class I: Implications for chronic
      lung rejection.
AB  - BACKGROUND: The role of non-complement activating antibodies (ncAbs) to
      mismatched donor human leukocyte antigen (HLA) in the pathogenesis of chronic
      lung rejection is not known. We used a murine model of obliterative airway
      disease (OAD) induced by Abs to major histocompatibility major histocompatibility
      complex (MHC) class I and serum from donor-specific Abs developed in human lung
      transplant (LTx) recipients to test the role of ncAbs in the development of OAD
      and bronchiolitis obliterans syndrome (BOS). METHODS: Anti-MHC ncAbs were
      administered intrabronchially in B.10 mice or in C3 knockout (C3KO) mice. Lungs
      were analyzed by histopathology. Lymphocytes secreting interleukin (IL)-17,
      interferon-gamma, or IL-10 to collagen V and K-alpha1 tubulin (Kalpha1T) were
      enumerated by enzyme-linked immunospot assay. Serum antibodies to collagen V and
      Kalpha1T were determined by enzyme-linked immunosorbent assay. Cytokine and
      growth factor expression in lungs was determined by real-time polymerase chain
      reaction. Donor-specific Abs from patients with BOS and control BOS-negative LTx
      recipients were analyzed by C1q assay. RESULTS: Administration of ncAbs in B.10
      mice or C3KO resulted in OAD lesions. There were significant increases in IL-17-
      and interferon-gamma-secreting cells to collagen V and Kalpha1T, along with serum
      Abs to these antigens. There was also augmented expression of monocyte
      chemotactic protein-1, IL-6, IL-1beta, vascular endothelial growth factor,
      transforming growth factor-beta, and fibroblastic growth factor in mice
      administered ncAbs by Day 3. Among 5 LTx recipients with BOS, only 1 had C1q
      binding donor-specific Abs. CONCLUSION: Complement activation by Abs to MHC class
      I is not required for development of OAD and human BOS. Therefore, anti-MHC
      binding to epithelial and endothelial cells can directly activate pro-fibrotic
      and pro-inflammatory cascades leading to immune response to self-antigens and
      chronic rejection.

PMID- 22980953
TI  - Intracardiac exposure for transventricular mitral valve ring annuloplasty repair
      during Dor ventriculoplasty.

PMID- 22980954
TI  - On the development of Arabic three-digit number processing in primary school
      children.
AB  - The development of two-digit number processing in children, and in particular the
      influence of place-value understanding, has recently received increasing research
      interest. However, place-value influences leading to decomposed processing have
      not yet been investigated for multi-digit numbers beyond the two-digit number
      range in children. Therefore, we evaluated the separate influences of hundreds,
      tens, and units on three-digit number processing by means of the hundred distance
      effect, the decade-hundred compatibility effect, and the unit-hundred
      compatibility effect in a longitudinal design from Grade 2 to Grade 4. In a
      number magnitude comparison task, a strong hundred distance effect indicated that
      the magnitudes of the hundreds digits were predominantly processed. We also
      observed indexes of decomposed parallel processing of hundreds and units digits
      but not of hundreds and tens digits. Regarding the developmental trajectories,
      the hundred distance effect and the unit-hundred compatibility effect showed a
      reliable trend to increase with grade level. However, both the significance and
      the increase with grade level of decomposed parallel processing were observed to
      be less consistent than expected. The latter is discussed in terms of different
      processing strategies as well as specificities differentiating between two- and
      three-digit numbers. Taken together, these are the first data showing decomposed
      processing of three-digit numbers in children. Yet, it must be noted that the
      results also indicate that findings from two-digit number processing cannot
      simply be generalized to the three-digit number range.

PMID- 22980955
TI  - Language nonselective lexical access in bilingual toddlers.
AB  - We examined how words from bilingual toddlers' second language (L2) primed
      recognition of related target words in their first language (L1). On critical
      trials, prime-target word pairs were either (a) phonologically related, with L2
      primes overlapped phonologically with L1 target words [e.g., slide (L2 prime)
      Kleid (L1 target, "dress")], or (b) phonologically related through translation,
      with L1 translations of L2 primes rhymed with the L1 target words [e.g., leg (L2
      prime, L1 translation, "Bein")-Stein (L1 target, "stone"). Evidence of
      facilitated target recognition in the phonological priming condition suggests
      language nonselective access but not necessarily lexical access. However, a late
      interference effect on target recognition in the phonological priming through
      translation condition provides evidence for language nonselective lexical access:
      The L2 prime (leg) could influence L1 target recognition (Stein) in this
      condition only if both the L2 prime (leg) and its L1 translation ("Bein") were
      concurrently activated. In addition, age- and gender-matched monolingual toddler
      controls showed no difference between conditions, providing further evidence that
      the results with bilingual toddlers were driven by cross-language activation. The
      current study, therefore, presents the first-ever evidence of cross-talk between
      the two languages of bilinguals even as they begin to acquire fluency in their
      second language.

PMID- 22980956
TI  - Localised mobilisation of metals, as measured by diffusive gradients in thin
      films, in soil historically treated with sewage sludge.
AB  - The two dimensional, small-scale, distribution of labile trace metals was
      investigated in a sandy loam soil historically treated with sewage sludge. After
      deployment of two DGT (diffusive gradients in thin-films) probes, their 1.8*15 cm
      windows were sliced into 5*5 mm and 5*8 mm rectangles to provide three vertical
      profiles with 5mm resolution. Both sets of profiles showed sharp maxima of Mn,
      Cd, Co, Cu, Ni and Zn, which varied systematically, both vertically and
      horizontally. The observed mobilisation of metals was highly localised, as each
      measurement corresponded to a volume of soil as little as 25-40 MUL. Regression
      analysis indicated mobilisation of Cd, Co, Cu, Ni and Zn were strongly linked to
      mobilisation of Mn, while there was a strong linkage between Pb and Fe
      mobilisation. Localised reductive dissolution of Mn oxides or a localised
      lowering of pH were considered as possible mechanisms.

PMID- 22980957
TI  - An insight into the influence of low dose irradiation pretreatment on the
      microbial decolouration and degradation of Reactive Red-120 dye.
AB  - The influence of low dose irradiation pretreatment on the microbial decolouration
      and degradation of Reactive Red-120 (RR-120) dye was investigated in detail by
      using Pseudomonas sp. SUK1. About 27%, 56% and 66% decolouration of 150 ppm RR
      120 dye solution was observed by applying 0, 0.5 and 1 kGy doses, respectively,
      in the first step followed by microbial treatment for 24 h under static
      condition. Similarly, about 70%, 88% and 90% TOC removal was observed by applying
      0, 0.5 and 1 kGy doses, respectively, in the first step followed by the microbial
      treatment for 96 h under static condition. The radiation induced fragmented
      products of RR-120 at doses of 0.5 and 1 kGy were investigated by FTIR and
      electrospray ionization-MS analysis. The induction of the enzymes viz. laccase,
      tyrosinase, azoreductase and NADH-2,6-dichlorophenol indophenol reductase was
      studied in the decolourised solution obtained after irradiating 150 ppm RR-120
      dye solution with 0 and 1 kGy doses followed by the microbial treatment for 96 h
      under static condition. The enzymatic degradation products were studied by FTIR,
      HPLC and GC-MS. The toxicity study of the treated dye solution on plants revealed
      the degradation of RR-120 into non-toxic products by combined radiation-microbial
      treatment. This study explores a reliable and promising way to use industrially
      viable dose (<=1 kGy) and microbial strain viz. Pseudomonas sp. SUK1 for
      permissible safe disposal of dye solutions from textile industries.

PMID- 22980958
TI  - Electrodialytic soil remediation enhanced by low frequency pulse current--overall
      chronopotentiometric measurement.
AB  - The effect of low frequency pulse current on decreasing the polarization and
      energy consumption during the process of electrodialytic soil remediation was
      investigated in the present work. The results indicated that the transportation
      of cations through the cation exchange membrane was the rate controlling step
      both in constant and pulse current experiments, thus responsible for the major
      energy consumption. After 180 h, a decrease in both the initial ohmic resistance
      in each pulse cycle and the resistance caused by concentration polarization of
      the anion exchange membrane were seen in the pulse current experiment compared to
      the constant current experiment. At the cation exchange membrane, only the
      resistance caused by concentration polarization decreased. In the soil
      compartment, an average of +60 mV overpotential caused by the polarization of the
      electric double layer of the clay particles was obtained from the Nernstian
      behavior simulation of the relaxation process, which was significantly lower than
      the ohmic voltage drop induced by pore fluid resistance. Therefore, the ohmic
      polarization was the major contributor to the energy consumption in the soil
      compartment and diminished by pulse current.

PMID- 22980959
TI  - Bench-scale gasification of cedar wood--part II: effect of operational conditions
      on contaminant release.
AB  - Here, we present the evolution profile of tar in the product gas during cedar
      biomass gasification. We also discuss the evolution of other contaminants (H(2)S,
      COS, NH(3), HCN, and HCl). The cedar wood was gasified under various operating
      conditions in a bench-scale externally heated updraft gasifier; this was followed
      by thermal reforming. Tar levels in the product gas were significantly affected
      by the operating conditions used. At a gasification temperature of 923 K, there
      was no clear relation between the evolution of phenolic tar in the product gas as
      a function of residence time. The evolution of PAH tar at a low gasification
      temperature was lower than the evolution of phenolic tar. With increasing
      temperature, the proportion of PAH tar content became significant. At a
      gasification temperature of 1223 K, increasing the residence time reduced the
      content of PAH tar owing to a catalytic effect associated with ash generation at
      high temperatures. Increasing the steam-to-carbon (S/C) ratio under thermal
      conditions had a slight effect on PAH conversion. However, increasing the
      equivalence ratio (ER) effectively reduced the tar levels. The conversion of fuel
      sulfur and fuel-nitrogen to volatile-sulfur and volatile-nitrogen, respectively,
      increased with increasing S/C ratio and ER. The evolutions of COS and HCN gases
      were much smaller than the evolution of H(2)S and NH(3). The evolution of HCl in
      the product gas decreased slightly with increasing ER. Increasing the S/C ratio
      decreased the HCl levels in the product gas. The effect of temperature on
      contaminant levels could not be fully understood due to limited availability of
      experimental data at various temperatures. We also compare our findings with data
      in the literature.

PMID- 22980960
TI  - In situ methane and nitrous oxide fluxes in soil from a transect in Hennequin
      Point, King George Island, Antarctic.
AB  - The study aimed at to determine the magnitude of the methane (CH(4)) and nitrous
      oxide (N(2)O) flux rates in soils at Hennequin Point, King George Island,
      Antarctic, under different slope positions, vegetal covers and presence of skuas,
      as well as to evaluate the main soil and climate factors that are involved with
      the flux of such gases. In situ gas sampling (closed chamber method) was
      performed in four sites along a transect involving a skua nesting field in a
      moraine with 5% and 100% of surface covered by vegetal, and two poor-drained
      soils in the toeslope (a bare alluvium soil and a poor-drained moss field with
      100% soil cover). Flux rates ranged from -0.86+/-0.45 to 2.75+/-1.52 MUg N(2)O-N
      m(-2) h(-1) and -12.26+/-3.05 to 1.42+/-1.31 MUg CH(4)-C m(-2) h(-1). The soil
      totally covered by vegetal in the skua field had the largest CH(4) influx rates.
      However, this benefic effect was counterbalanced by the greatest N(2)O efflux
      rates from this soil, resulting in the largest contribution to the global warming
      potential among the soils evaluated. Flux rates were closely related to soil
      temperature, but no significant relation was observed with mineral N contents and
      water-filled pore space. In turn, accumulated CH(4) and N(2)O emissions were
      closely related to the total N and total organic C stocks in the soil. Net CH(4)
      influx predominated even in the poor-drained soils, suggesting that the coarse
      soil texture avoided critical anaerobic conditions. No significant changes in
      flux rates were observed for sampling time along the day.

PMID- 22980961
TI  - Bench-scale gasification of cedar wood--part I: effect of operational conditions
      on product gas characteristics.
AB  - The present study was conducted within the framework of R&D activities on the
      development of gasification and reforming technologies for energy and chemical
      recovery from biomass resources. Gasification of the Japanese cedar wood has been
      investigated under various operating conditions in a bench-scale externally
      heated updraft gasifier; this was followed by thermal reforming. Parametric tests
      by varying the residence times, gasification temperatures, equivalence ratios
      (ERs) and steam-to-carbon (S/C) ratios were performed to determine their effects
      on the product gas characteristics. Thermodynamic equilibrium calculations were
      preformed to predict the equilibrium gas composition and compared with the
      experimental value. We found that the product gas characteristics in terms of the
      H(2)/CO ratio, CO(2)/CO ratio, and CH(4) and lighter hydrocarbons concentrations
      are significantly affected by the operating conditions used. Increasing the
      residence time decreased the CO(2)/CO ratio; however, a nominal effect was
      noticed on H(2) concentration as a function of the residence time. At sufficient
      residence time, increasing the temperature led to higher H(2) yields, CO
      efficiency and higher heating value (HHV) of the product gas. The presence of
      steam during gasification effectively enhanced the proportion of H(2) in the
      product gas. However, higher S/C ratio reduced the HHV of the product gas.
      Increasing the ER from 0 to 0.3 increased the H(2) yields and CO efficiency and
      decreased the HHV of the product gas. The evolution of CH(4) and lighter
      hydrocarbons at low gasification temperatures was relatively higher than that at
      high temperature gasification. The evolution of CH(4) and lighter hydrocarbons at
      high gasification temperatures hardly varied over the investigated operating
      conditions.

PMID- 22980962
TI  - Application of micronucleus test and comet assay to evaluate BTEX biodegradation.
AB  - The BTEX (benzene, toluene, ethylbenzene and xylene) mixture is an environmental
      pollutant that has a high potential to contaminate water resources, especially
      groundwater. The bioremediation process by microorganisms has often been used as
      a tool for removing BTEX from contaminated sites. The application of biological
      assays is useful in evaluating the efficiency of bioremediation processes,
      besides identifying the toxicity of the original contaminants. It also allows
      identifying the effects of possible metabolites formed during the biodegradation
      process on test organisms. In this study, we evaluated the genotoxic and
      mutagenic potential of five different BTEX concentrations in rat hepatoma tissue
      culture (HTC) cells, using comet and micronucleus assays, before and after
      biodegradation. A mutagenic effect was observed for the highest concentration
      tested and for its respective non-biodegraded concentration. Genotoxicity was
      significant for all non-biodegraded concentrations and not significant for the
      biodegraded ones. According to our results, we can state that BTEX is mutagenic
      at concentrations close to its water solubility, and genotoxic even at lower
      concentrations, differing from some described results reported for the mixture
      components, when tested individually. Our results suggest a synergistic effect
      for the mixture and that the biodegradation process is a safe and efficient
      methodology to be applied at BTEX-contaminated sites.

PMID- 22980964
TI  - Benefit of bivalirudin versus heparin after transradial and transfemoral
      percutaneous coronary intervention.
AB  - Bivalirudin, a direct thrombin inhibitor, has been shown to reduce major bleeding
      and provide a better safety profile compared to unfractionated heparin (UFH) in
      patients undergoing percutaneous coronary intervention (PCI) through transfemoral
      access. Data pertaining to the clinical benefit of bivalirudin compared to UFH
      monotherapy in patients undergoing transradial PCI are lacking. The present study
      sought to compare the in-hospital net clinical adverse events, including death,
      myocardial infarction, target vessel revascularization, and bleeding, for these 2
      antithrombotic regimens for all patients at a tertiary care, high-volume radial
      center. From April 2009 to February 2011, all patients treated with bivalirudin
      were matched by access site to those receiving UFH. The patients in the
      bivalirudin group (n = 125) were older (72 +/- 13 years vs 66 +/- 11 years; p
      <0.0001), more often had chronic kidney disease (51% vs 30%; p = 0.0012), and
      more often underwent primary PCI (30% vs 14%, p <0.0037) than the UFH-treated
      patients (n = 125). A radial approach was used in 71% of both groups. The
      baseline bleeding risk according to Mehran's score was similar in both groups (14
      +/- 9 vs 15 +/- 8, p = 0.48). In-hospital mortality was 2% in both groups (p =
      1.00). No difference in net clinical adverse events or ischemic or bleeding
      complications was detected between the 2 groups. Bivalirudin reduced both
      ischemic and bleeding events in femoral-treated patients, but no such clinical
      benefit was observed in the radial-treated patients. In conclusion, as
      periprocedural PCI bleeding avoidance strategies have become paramount to
      optimize the clinical benefit, the interaction between bivalirudin and radial
      approach deserves additional investigation.

PMID- 22980963
TI  - Risk factors for coronary artery calcium among patients with chronic kidney
      disease (from the Chronic Renal Insufficiency Cohort Study).
AB  - Cardiovascular disease is the leading cause of death in patients with chronic
      kidney disease (CKD). We examined the cross-sectional association between novel
      risk factors and coronary artery calcium (CAC) measured using electron beam
      computed tomography or multidetector computed tomography among 2,018 patients
      with CKD. Using the total Agatston scores, the participants were classified as
      having no (0), moderate (>0-100), or high (>100) CAC. After adjustment for age,
      gender, race, study sites, cigarette smoking, previous cardiovascular disease,
      hypertension, and diabetes, the use of lipid-lowering drugs, body mass index,
      waist circumference, and cystatin C, several novel risk factors were
      significantly associated with high CAC. For example, the odds ratios of high CAC
      associated with 1 SD greater level of risk factors were 1.20 (95% confidence
      interval 1.04 to 1.38) for serum calcium, 1.21 (95% confidence interval 1.04 to
      1.41) for serum phosphate, 0.83 (95% confidence interval 0.71 to 0.97) for log
      (total parathyroid hormone), 1.21 (95% confidence interval 1.03 to 1.43) for log
      (homeostasis model assessment-insulin resistance), and 1.23 (95% confidence
      interval 1.04 to 1.45) for hemoglobin A1c. Additionally, the multivariate
      adjusted odds ratio for 1 SD greater level of cystatin C was 1.31 (95% confidence
      interval 1.14 to 1.50). Serum high-sensitive C-reactive protein, interleukin-6,
      tumor necrosis factor-alpha, and homocysteine were not statistically
      significantly associated with high CAC. In conclusion, these data indicate that
      abnormal calcium and phosphate metabolism, insulin resistance, and declining
      kidney function are associated with the prevalence of high CAC, independent of
      the traditional risk factors in patients with CKD. Additional studies are
      warranted to examine the causal effect of these risk factors on CAC in patients
      with CKD.

PMID- 22980965
TI  - Fluoroscopy-induced chronic radiation dermatitis.
AB  - A 62-year-old man with a history of 2 previous cardiac catheterizations presented
      with an itchy, nontender skin lesion over his right scapula. The skin lesion had
      been present for >5 years. Review of the medical records found evidence of a
      prolonged and complicated cardiac catheterization 8 years previously. Physical
      examination revealed an 8 * 6 cm, well-demarcated, erythematous reticulated
      atrophic plaque with telangiectasias and ulceration. Biopsy confirmed histologic
      changes consistent with radiation dermatitis. In conclusion, the characteristic
      histologic findings of radiation dermatitis, along with the location over the
      right scapula and the history of prolonged fluoroscopic exposure during cardiac
      catheterization, led to the clinical diagnosis of fluoroscopy-induced chronic
      radiation dermatitis.

PMID- 22980966
TI  - Usefulness of aspiration of pulmonary emboli and prolonged local thrombolysis to
      treat pulmonary embolism.
AB  - Catheter-based treatment of pulmonary embolism (PE) has been demonstrated to be
      successful in case reports and small series. The investigators report the results
      of a novel, pharmacomechanical approach with prolonged infusion of urokinase in
      the occluded pulmonary arteries (PAs). Manual aspiration of thrombus using guide
      catheters was followed by introduction of thrombolysis catheters and a local
      bolus of urokinase. The lysis catheters were left in place, and repeat PA cine
      angiography and right-sided cardiac catheterization was performed 3 days later. A
      total of 63 patients (mean age 60 +/- 15 years) were treated over 8 years: 17
      patients (27%) had massive and 46 patients (73%) submassive PE. The mean PA
      pressure was 35 +/- 10 mm Hg, and 54% had central bilateral PE. Five patients
      died, 1 before, 1 during, and 3 after the intervention. Nine patients (14%) had
      major bleeds (hemoglobin decrease >30 g/L), but in none of these patients was
      bleeding the reason for fatal outcome. After 3.3 +/- 1.0 days, 49 of 58 living
      patients (84%) were restudied. In 29 (59%), there was a reduction of thrombotic
      burden by >90%, and in 14 (29%), the reduction was 50% to 90%. Mean PA pressure
      was reduced from 33 +/- 8 to 21 +/- 7 mm Hg (p <0.001), and this was not
      dependent on a reduction of thrombus. In conclusion, manual aspiration and
      application of prolonged thrombolysis is feasible and safe. Improvement of PA
      pressures is impressive and there is no correlation between morphologic
      disappearance of thrombus and normalization of PA pressures.

PMID- 22980967
TI  - Effect of pulmonary valve replacement on left ventricular function in patients
      with tetralogy of Fallot.
AB  - Pulmonary valve regurgitation is the most common complication after complete
      repair of tetralogy of Fallot. The benefits of pulmonary valve replacement (PVR)
      on right ventricular (RV) volumes is well established. However, the effect on
      left ventricular (LV) function is still debated. We aimed to determine the
      evolution of LV function after PVR and assess the contribution of the
      interventricular septum (IVS) motion. A total of 21 patients (mean age 30.1 +/-
      14.1 years) presenting with a history of complete repair of tetralogy of Fallot
      and requiring PVR prospectively underwent cardiac magnetic resonance imaging
      before and after PVR to measure the end-diastolic volume (EDV), end systolic
      volume, and ejection fraction for the LV and RV chambers. Maximal excursion of
      the IVS was also calculated to quantify abnormal septal motion. The LV-EDV and LV
      end systolic volume was 80 +/- 27 and 40 +/- 19.5 ml/m(2) before PVR and 81.5 +/-
      23 and 35 +/- 14 ml/m(2) after PVR, respectively, leading to a significant
      increase in LV ejection fraction of 6.1 +/- 4.9% (51 +/- 8.2% before and 57 +/-
      6.8% after PVR, p = 0.0003). Also, a significant reduction in RV-EDV (p = 0.0001)
      and RV end-systolic volume (p = 0.0001) was seen but without improvement in the
      RV ejection fraction. The maximum IVS excursion decreased after PVR (9.2 +/- 3.4
      mm before and 6.8 +/- 3.6 mm after; p = 0.002). LV ejection fraction improvement
      correlated with RV-EDV before PVR (rho = 0.43; p = 0.049). The maximum IVS
      excursion correlated with RV-EDV before and after PVR but was independent of LV
      ejection fraction improvement. In conclusion, the results of the present study
      have demonstrated a significant improvement in LV ejection fraction after PVR
      that correlated with the pre-PVR RV-EDV but was independent of IVS motion
      improvement.

PMID- 22980968
TI  - Association of epicardial fat, hypertension, subclinical coronary artery disease,
      and metabolic syndrome with left ventricular diastolic dysfunction.
AB  - Epicardial fat is a metabolically active fat depot that is strongly associated
      with obesity, metabolic syndrome, and coronary artery disease (CAD). The relation
      of epicardial fat to diastolic function is unknown. We sought to (1) understand
      the relation of epicardial fat volume (EFV) to diastolic function and (2)
      understand the role of EFV in relation to potential risk factors (hypertension,
      subclinical CAD, and metabolic syndrome) of diastolic dysfunction in apparently
      healthy subjects with preserved systolic function and no history of CAD. We
      studied 110 consecutive subjects (65% men, 55 +/- 13 years old, mean body mass
      index 28 +/- 5 kg/m(2)) who underwent cardiac computed tomography and
      transthoracic echocardiography within 6 months as part of a self-referred health
      screening program. Exclusion criteria included history of CAD, significant
      valvular disease, systolic dysfunction (left ventricular ejection fraction <50%).
      Diastolic function was defined according to American Society of Echocardiography
      guidelines. EFV was measured using validated cardiac computed tomographic
      software by 2 independent cardiologists blinded to clinical and echocardiographic
      data. Hypertension and metabolic syndrome were present in 60% and 45%,
      respectively. Subclinical CAD was identified in 20% of the cohort. Diastolic
      dysfunction was present in 45 patients. EFV was an independent predictor of
      diastolic dysfunction, mean peak early diastolic mitral annular velocity, and
      ratio of early diastolic filling to peak early diastolic mitral annular velocity
      (p = 0.01, <0.0001, and 0.001, respectively) with incremental contribution to
      other clinical factors. In conclusion, EFV is an independent predictor of
      impaired diastolic function in apparently healthy overweight patients even after
      accounting for associated co-morbidities such as metabolic syndrome,
      hypertension, and subclinical CAD.

PMID- 22980969
TI  - Increased volume of tracheal aspirate fluid predicts the development of
      bronchopulmonary dysplasia.
AB  - BACKGROUND: Elevated cytokine concentrations were observed in tracheal aspirate
      fluid (TAF) of infants on mechanical ventilation who subsequently developed
      bronchopulmonary dysplasia (BPD). However, there are few reports that
      systematically evaluate the amount of TAF as an indicator of BPD development.
      AIM: To clarify whether TAF volume during the first week of life predicts BPD
      development in extremely low gestational age newborns (ELGANs). STUDY DESIGN: We
      analyzed 51 infants, born at gestational age of <28 weeks and ventilated for more
      than 7 days after birth, among whom, 26 were diagnosed with BPD based on the
      clinical definition of oxygen dependence at 36 weeks postmenstrual age (BPD
      group) and 25 were included in the non-BPD group. Sum of TAF scores (STS) was
      calculated by semi-quantification of TAF volume at each suctioning and the
      suctioning frequency during the first week of life. RESULTS: STS was
      significantly higher in the BPD group than in the non-BPD group (median
      (interquartile range): 77 (29-126) vs. 28 (22-59), p<0.001). STS (cut-off, 60)
      with area under the curve in receiver operating analysis of 0.75 was
      significantly predictive of BPD development. Multivariate logistic regression
      analysis adjusted for perinatal characteristics showed that STS>=60 was a
      significant risk factor for BPD development (odds ratio, 7.50; confidence
      interval, 1.16-48.40, p=0.034). CONCLUSION: Increased TAF volume during the first
      week of life was an independent predictor for BPD development in ventilated
      ELGANs, indicating that increased pulmonary capillary permeability may influence
      the pathogenesis of BPD.

PMID- 22980970
TI  - Behind the movement.
AB  - This year, the Albert Lasker Basic Medical Research Award will be shared by
      Michael Sheetz, James Spudich, and Ronald Vale for discoveries concerning the
      biophysical actions of cytoskeletal motor-protein machines that move cargo within
      cells, contract muscles, and enable cell motility.

PMID- 22980971
TI  - Liver transplantation: from inception to clinical practice.
AB  - The 2012 Lasker-DeBakey Clinical Medical Research Award will be conferred on
      Thomas Starzl of the University of Pittsburgh School of Medicine in Pittsburgh,
      Pennsylvania, USA and Roy Calne of the University of Cambridge in Cambridge, UK.
      They are recognized for pioneering the development of liver transplantation, an
      intervention that saves 20,000 lives world-wide each year.

PMID- 22980972
TI  - Pure genes, pure genius.
AB  - The 2012 Albert Lasker Special Achievement Award in Medical Science will be
      shared by Donald Brown and Tom Maniatis for their scientific work leading to the
      purification and study of single genes by physical and molecular biological
      methodologies. Brown and Maniatis are also recognized for their extraordinary
      commitment and generosity in promoting the careers of young scientists. The
      impact of these accomplishments has transformed biological and medical science
      over the past four decades.

PMID- 22980973
TI  - Diabetic beta Cells: To Be or Not To Be?
AB  - beta cell dysfunction with subsequent apoptosis is considered a significant
      contributor to the development of type 2 diabetes. Emerging data from Talchai et
      al. suggest beta cell dedifferentiation as an alternative mechanism of insulin
      insufficiency that might be more amenable to intervention in at least a subset of
      patients.

PMID- 22980974
TI  - Building bridges for spinal cord repair.
AB  - For nearly a century, neuroscientists have sought to restore neurological
      function across spinal cord lesions. Lu et al. now present significant progress
      toward this goal, showing in rats that transplanted neural stem cells establish a
      functional bridge across completely transected spinal cords.

PMID- 22980975
TI  - Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.
AB  - Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is
      responsible for more than 500,000 deaths per year worldwide. Here, we report
      exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs.
      These analyses revealed a mean exonic somatic mutation rate of 12.0
      events/megabase and identified the majority of genes previously reported as
      significantly mutated in lung adenocarcinoma. In addition, we identified
      statistically recurrent somatic mutations in the splicing factor gene U2AF1 and
      truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context
      specific mutation signatures grouped the sample set into distinct clusters that
      correlated with smoking history and alterations of reported lung adenocarcinoma
      genes. Whole-genome sequence analysis revealed frequent structural
      rearrangements, including in-frame exonic alterations within EGFR and SIK2
      kinases. The candidate genes identified in this study are attractive targets for
      biological characterization and therapeutic targeting of lung adenocarcinoma.

PMID- 22980976
TI  - Genomic landscape of non-small cell lung cancer in smokers and never-smokers.
AB  - We report the results of whole-genome and transcriptome sequencing of tumor and
      adjacent normal tissue samples from 17 patients with non-small cell lung
      carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in
      the coding sequence, with an average mutation frequency more than 10-fold higher
      in smokers than in never-smokers. Novel alterations in genes involved in
      chromatin modification and DNA repair pathways were identified, along with DACH1,
      CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality
      patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations
      were present in the founder clones, suggesting possible roles in cancer
      initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as
      novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly
      altered in lung cancer, along with perturbations in 54 genes that are potentially
      targetable with currently available drugs.

PMID- 22980977
TI  - Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.
AB  - DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark
      that is critical for various biological and pathological processes. 5-mC can be
      converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation
      (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an
      epigenetic hallmark of melanoma, with diagnostic and prognostic implications.
      Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma
      epigenome. We show that downregulation of isocitrate dehydrogenase 2 (IDH2) and
      TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in
      melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing
      active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival
      in animal models. Thus, our study reveals a critical function of 5-hmC in
      melanoma development and directly links the IDH and TET activity-dependent
      epigenetic pathway to 5-hmC-mediated suppression of melanoma progression,
      suggesting a new strategy for epigenetic cancer therapy.

PMID- 22980978
TI  - Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination
      of transcription by RNAPII.
AB  - Transcription elongation is increasingly recognized as an important mechanism of
      gene regulation. Here, we show that microprocessor controls gene expression in an
      RNAi-independent manner. Microprocessor orchestrates the recruitment of
      termination factors Setx and Xrn2, and the 3'-5' exoribonuclease, Rrp6, to
      initiate RNAPII pausing and premature termination at the HIV-1 promoter through
      cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product,
      which generates a small RNA that is required to mediate potent transcriptional
      repression and chromatin remodeling at the HIV-1 promoter. Using chromatin
      immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we
      identified cellular gene targets whose transcription is modulated by
      microprocessor. Our study reveals RNAPII pausing and premature termination
      mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and
      Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation.

PMID- 22980979
TI  - RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling.
AB  - Ubiquitin-dependent signaling during the DNA damage response (DDR) to double
      strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting
      histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and
      RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates
      H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them.
      Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168
      catalyzes the monoubiquitination of the histones specifically on K13-15.
      Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged
      residue determines whether nucleosomal proteins are recognized. We find that K63
      ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination
      at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones
      but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per
      se are insufficient for signaling, but RNF168 target ubiquitination is required
      for DDR.

PMID- 22980980
TI  - Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1.
AB  - The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous
      cues, including amino acids, which promote mTORC1 translocation to the lysosomal
      surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the
      Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a
      signaling system that is necessary for amino acid sensing by mTORC1. Amino acids
      stimulate the binding of guanosine triphosphate to RagA and RagB but the factors
      that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and
      C7orf59 as two additional Ragulator components that are required for mTORC1
      activation by amino acids. The expanded Ragulator has nucleotide exchange
      activity toward RagA and RagB and interacts with the Rag heterodimers in an amino
      acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into
      how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide
      exchange factor (GEF) for the Rag GTPases.

PMID- 22980981
TI  - Single-cell expression analyses during cellular reprogramming reveal an early
      stochastic and a late hierarchic phase.
AB  - During cellular reprogramming, only a small fraction of cells become induced
      pluripotent stem cells (iPSCs). Previous analyses of gene expression during
      reprogramming were based on populations of cells, impeding single-cell level
      identification of reprogramming events. We utilized two gene expression
      technologies to profile 48 genes in single cells at various stages during the
      reprogramming process. Analysis of early stages revealed considerable variation
      in gene expression between cells in contrast to late stages. Expression of Esrrb,
      Utf1, Lin28, and Dppa2 is a better predictor for cells to progress into iPSCs
      than expression of the previously suggested reprogramming markers Fbxo15, Fgf4,
      and Oct4. Stochastic gene expression early in reprogramming is followed by a late
      hierarchical phase with Sox2 being the upstream factor in a gene expression
      hierarchy. Finally, downstream factors derived from the late phase, which do not
      include Oct4, Sox2, Klf4, c-Myc, and Nanog, can activate the pluripotency
      circuitry.

PMID- 22980982
TI  - Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell
      failure.
AB  - Diabetes is associated with beta cell failure. But it remains unclear whether the
      latter results from reduced beta cell number or function. FoxO1 integrates beta
      cell proliferation with adaptive beta cell function. We interrogated the
      contribution of these two processes to beta cell dysfunction, using mice lacking
      FoxO1 in beta cells. FoxO1 ablation caused hyperglycemia with reduced beta cell
      mass following physiologic stress, such as multiparity and aging. Surprisingly,
      lineage-tracing experiments demonstrated that loss of beta cell mass was due to
      beta cell dedifferentiation, not death. Dedifferentiated beta cells reverted to
      progenitor-like cells expressing Neurogenin3, Oct4, Nanog, and L-Myc. A subset of
      FoxO1-deficient beta cells adopted the alpha cell fate, resulting in
      hyperglucagonemia. Strikingly, we identify the same sequence of events as a
      feature of different models of murine diabetes. We propose that dedifferentiation
      trumps endocrine cell death in the natural history of beta cell failure and
      suggest that treatment of beta cell dysfunction should restore differentiation,
      rather than promoting beta cell replication.

PMID- 22980983
TI  - A spatially-organized multicellular innate immune response in lymph nodes limits
      systemic pathogen spread.
AB  - The lymphatic network that transports interstitial fluid and antigens to lymph
      nodes constitutes a conduit system that can be hijacked by invading pathogens to
      achieve systemic spread unless dissemination is blocked in the lymph node itself.
      Here, we show that a network of diverse lymphoid cells (natural killer cells,
      gammadelta T cells, natural killer T cells, and innate-like CD8+ T cells) are
      spatially prepositioned close to lymphatic sinus-lining sentinel macrophages
      where they can rapidly and efficiently receive inflammasome-generated IL-18 and
      additional cytokine signals from the pathogen-sensing phagocytes. This leads to
      rapid IFNgamma secretion by the strategically positioned innate lymphocytes,
      fostering antimicrobial resistance in the macrophage population. Interference
      with this innate immune response loop allows systemic spread of lymph-borne
      bacteria. These findings extend our understanding of the functional significance
      of cellular positioning and local intercellular communication within lymph nodes
      while emphasizing the role of these organs as highly active locations of innate
      host defense.

PMID- 22980984
TI  - Chemokine guidance of central memory T cells is critical for antiviral recall
      responses in lymph nodes.
AB  - A defining feature of vertebrate immunity is the acquisition of immunological
      memory, which confers enhanced protection against pathogens by mechanisms that
      are incompletely understood. Here, we compared responses by virus-specific naive
      T cells (T(N)) and central memory T cells (T(CM)) to viral antigen challenge in
      lymph nodes (LNs). In steady-state LNs, both T cell subsets localized in the deep
      T cell area and interacted similarly with antigen-presenting dendritic cells.
      However, upon entry of lymph-borne virus, only T(CM) relocalized rapidly and
      efficiently toward the outermost LN regions in the medullary, interfollicular,
      and subcapsular areas where viral infection was initially confined. This rapid
      peripheralization was coordinated by a cascade of cytokines and chemokines,
      particularly ligands for T(CM)-expressed CXCR3. Consequently, in vivo recall
      responses to viral infection by CXCR3-deficient T(CM) were markedly compromised,
      indicating that early antigen detection afforded by intranodal chemokine guidance
      of T(CM) is essential for efficient antiviral memory.

PMID- 22980986
TI  - SnapShot: membrane curvature sensors and generators.

PMID- 22980985
TI  - Long-distance growth and connectivity of neural stem cells after severe spinal
      cord injury.
AB  - Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices
      containing growth factor cocktails and grafted to sites of severe spinal cord
      injury. Grafted cells differentiated into multiple cellular phenotypes, including
      neurons, which extended large numbers of axons over remarkable distances.
      Extending axons formed abundant synapses with host cells. Axonal growth was
      partially dependent on mammalian target of rapamycin (mTOR), but not Nogo
      signaling. Grafted neurons supported formation of electrophysiological relays
      across sites of complete spinal transection, resulting in functional recovery.
      Two human stem cell lines (566RSC and HUES7) embedded in growth-factor-containing
      fibrin exhibited similar growth, and 566RSC cells supported functional recovery.
      Thus, properties intrinsic to early-stage neurons can overcome the inhibitory
      milieu of the injured adult spinal cord to mount remarkable axonal growth,
      resulting in formation of new relay circuits that significantly improve function.
      These therapeutic properties extend across stem cell sources and species.

PMID- 22980987
TI  - [Myxoid neurofibroma of the thumb].
AB  - Myxoid neurofibroma (MN) is a benign tumor of poorly identified perineural cell
      origin. We report a case of NM of left thumb and discuss the main differential
      diagnosis. CASE REPORT: A 34-year-old woman presented with a painless, slowly
      progressive tumor of the left thumb of 6 months duration. This tumor had recurred
      after resection done 26 years before. Clinical examination revealed a tumor on
      the anterior surface of the left thumb, painless, firm, 4*3cm, ulcerated and
      covered with thin telangiectasia. The X-ray of the phalanx showed no alteration
      to the underlying bone. The histopathological study of a skin biopsy reported a
      myxoid neurofibroma. Excision of the lesion was performed with preservation of
      the nail. Neither the patient nor her family members had neurofibromatosis. The
      outcome was favorable and no recurrence was noted after 18 months of follow-up.
      COMMENTS: The usual sites of the MN are the face, shoulders, arms, and periungual
      regions. It is usually a solitary lesion; however, lesions may be multiple or
      recur after initial incomplete excision as in our patient. It must be considered
      in the differential diagnosis of tumors of the extremities. We report this case
      because of the rarity of both the tumor and its site.

PMID- 22980988
TI  - Osteochondritis dissecans of the capitellum: autologous osteochondral
      mosaicplasty: a case report.
AB  - The etiology of osteochondritis dissecans (OCD) of the capitellum is unknown but
      has generally been attributed to repetitive microtrauma or ischemia. We present a
      case report of a handball player with OCD of the capitellum. Preoperatively, he
      complained of elbow pain. CT imaging showed the injury. This patient was treated
      with mosaicplasty harvested from the lateral femoral condyle. He returned to his
      full former sports activities within 6months of surgery. The continuity of the
      cartilage layer between the osteochondral graft and the capitellum was shown on
      CT arthrogram images at 12months after surgery. We believe that mosaicplasty
      gives successful results with end-stage OCD of the capitellum.

PMID- 22980989
TI  - [Unusual rupture of a flexor profundus tendon in a rock climber].
AB  - Injuries of the flexor pulleys are common in rock climbers. Ruptures of the
      flexor profundus tendons are less common and take place almost exclusively in
      zone I at the level of the distal phalangeal insertion of the tendon. We report
      the case of a 48 years old rock climber who sustained an uncommon complete
      rupture of the flexor profundus tendon of the long finger during a monodigital
      grip. The tear was localized in zone III, immediately distal to the distal edge
      of the carpal tunnel. Tendon repair by direct suture followed by early active
      mobilization led to a satisfactory result. To the best of our knowledge, this is
      the first description of this type of injury in a rock climber.

PMID- 22980990
TI  - [Osteoid osteoma of the phalanx in children and diagnostic problems: report of
      one case].
AB  - Osteoid osteoma is a benign osseous tumor of unknown origin, which affects
      preferentially the long bones. The localization in the phalanx is unusual and
      difficult to diagnose. We present a case of a 13-year-old girl, presenting with a
      painful swelling of the first phalanx of the right middle finger of 5 months
      duration, not responding to anti-inflammatory drugs. The diagnosis of
      tuberculosis of the bones was suggested at first (tuberculosis is endemic in our
      country), but the biology and the bone biopsy did not confirm the diagnosis. The
      lesion was excised, and the histology confirmed the diagnosis of osteoid osteoma.
      Through our observation and after a review of the literature, we analyze the
      clinical and paraclinical appearance of this uncommon localization, the
      differential diagnosis, and finally the therapeutic possibilities.

PMID- 22980991
TI  - Amandys((r)) implant: novel pyrocarbon arthroplasty for the wrist.
AB  - OBJECTIVES: Post-traumatic, arthritic or degenerative destruction of the
      midcarpal and radiocarpal joints are difficult to treat. A new arthroplasty with
      a free interposition pyrocarbon implant, Amandys((r)), is proposed for the
      treatment of extensive destruction of midcarpal and radiocarpal joints.
      Preliminary results are reported. METHODS: The prospective series included 25
      patients, 15 males and 10 females with a mean age of 60. The indications were
      degenerative, post-traumatic or rheumatoid destruction of the wrist. Sixty
      percent of the patients had already had surgery on their wrist before the
      operation. The mean follow-up was 24months. RESULTS: Three patients had a
      reoperation: two for a repositioning of the implant and one for a styloidectomy.
      At the last follow-up, the mean grip strength was 16kg (51% of the contralateral
      side), the mean range of motion in flexion-extension was 68 degrees . Mean
      strength and range of motion did not change significantly with the operation.
      Pain and function showed significant improvement. The mean pain score decreased
      from 6.7/10 to 3.7/10 postoperatively. The mean PRWE score decreased from 61/100
      to 32/100.The mean QuickDash score decreased from 63/100 to 36/100. Ninety-six
      percent of the patients were satisfied or very satisfied. No dislocation or
      subsidence of the implant was noticed. CONCLUSIONS: This minimally invasive
      pyrocarbon interposition increases the possibilities for the treatment of
      extensive articular destructions of the wrist. Indications must be limited to a
      well-aligned wrist with competent capsuloligamentous structure. This new
      arthroplasty is a reliable alternative to other surgical options, which are more
      radical or invasive such as total arthrodesis or total wrist prosthesis.

PMID- 22980992
TI  - [Palmar and plantar keloid in a black African male].
AB  - The keloid scar is a fibrous skin tumor, intradermal, and exuberant. It is
      commonly found on the glabrous skin. The keloid of the palms and soles are rare.
      Small series are reported in English literature. The authors report a case of
      large keloids located on both palms and soles, within a context of keloid
      disease, in a man of 37 years. On the left hand, the keloid scar caused a partial
      syndactyly IV-V. Large keloid tumors occupied the inner edge and, weight-bearing
      areas of both feet. These tumors rendered wearing of shoes impossible and
      interfered with walking. The treatment consisted of total excision of palmar and
      plantar keloid tumors. The residual defects were covered by a total skin graft
      taken from the suprapubic region. The results were satisfactory aesthetically,
      functionally and psychosocially.

PMID- 22980993
TI  - Arthroscopic criteria for dating wrist sprains.
AB  - OBJECTIVES: Dating wrist sprains has therapeutic and medicolegal importance. The
      authors propose a study validating three arthroscopic criteria to date the
      trauma. METHODS: The authors analyzed statistically one hundred arthroscopies
      performed between 1999 and 2008 after wrist sprains. They suggest three criteria
      to date the injury. They are: turbidity of synovial fluid (assessed T0 to T4),
      hemorrhagic infiltration of the synovium (evaluated S0 to S2), and the aspect of
      the articular cartilage (assessed C0 to C4). RESULTS: The importance of turbidity
      is significant with P<0.001. The importance of synovitis is significant with
      P<0.001. The extent of cartilage degradation is significant with P<0.01. These
      three criteria have also a very significant predictability. The authors
      distinguish four posttraumatic periods: the immediate period, less than 2 weeks,
      corresponding to T3/T4, S2, C0; the acute period from 2 to 6 weeks, corresponding
      to T1/T2, S1, C1/C2; the subacute period from 6 weeks to 6 months, corresponding
      to T0, S1, C3; the chronic period beyond 6 months, corresponding to T0, S0, C4.
      The association T2/T4, S2, C4 is clearly an acute injury with a previous
      pathologic situation. CONCLUSIONS: The arthroscopic criteria for dating a wrist
      sprain are simple to estimate. They are used to define the immediate, acute,
      subacute or chronic posttraumatic periods, and a previous pathologic situation.
      The choice of surgical indication is facilitated and an objective estimation of
      the length of lesion is useful in the forensic setting.

PMID- 22980994
TI  - [Dorsal radiocarpal joint dislocation for an 85-years-old woman].
AB  - The authors report the case of a dorsal, closed, radiocarpal dislocation with a
      small posterior marginal fracture of the radius, in an 85-year-old woman, without
      violent trauma (fall from her height). The dislocation was reduced by traction
      and the wrist immobilized in a plaster cast for 6 weeks. Six months after the
      accident, the patient had resumed her activities without pain with a diminished
      range of motion. This dislocation is exceptional at this age. In our case, the
      functional outcome was good after orthopaedic treatment.

PMID- 22980995
TI  - Autoproteolytic and catalytic mechanisms for the beta-aminopeptidase BapA--a
      member of the Ntn hydrolase family.
AB  - The beta-aminopeptidase BapA from Sphingosinicella xenopeptidilytica belongs to
      the N-terminal nucleophile (Ntn) hydrolases of the DmpA-like family and has the
      unprecedented property of cleaving N-terminal beta-amino acid residues from
      peptides. We determined the crystal structures of the native (alphabeta)4
      heterooctamer and of the 153 kDa precursor homotetramer at a resolution of 1.45
      and 1.8 A, respectively. These structures together with mutational analyses
      strongly support mechanisms for autoproteolysis and catalysis that involve
      residues Ser250, Ser288, and Glu290. The autoproteolytic mechanism is different
      from the one so far described for Ntn hydrolases. The structures together with
      functional data also provide insight into the discriminating features of the
      active site cleft that determine substrate specificity.

PMID- 22980996
TI  - Effectiveness of nutritional supplementation on muscle mass in treatment of
      sarcopenia in old age: a systematic review.
AB  - BACKGROUND: Much interest has been focused on nutritional treatment of
      sarcopenia, loss of muscle mass and performance associated to aging; however, its
      benefits are unclear. OBJECTIVE: To analyze the relevance of nutritional
      treatment of sarcopenia and assess the effects of supplementation on muscle mass
      and function within the aged population. METHODS: We searched Medline and the
      Cochrane Library for controlled trials published between 1991 and 2012. We have
      assessed the quality, type of intervention, the cohort used, the way muscle mass
      was measured, and the outcomes of the various studies. RESULTS: We have included
      17 studies, with a total of 1287 patients, aged between 65 and 85 on average. An
      improvement in muscle mass was proven, whether measured with bioelectrical
      impedance analysis or dual energy x-ray absorptiometry, and an improvement in
      strength was also proven. CONCLUSION: Nutritional supplementation is effective in
      the treatment of sarcopenia in old age, and its positive effects increase when
      associated with physical exercise. The main limitation of this treatment is lack
      of long-term adherence. A healthy diet associated with a physically active
      lifestyle and possibly with aerobic exercise are the basis of healthy aging,
      which is the aim of all doctors treating aged people must seek.

PMID- 22980997
TI  - Quality of life of patients with Korsakoff's syndrome and patients with dementia:
      a cross-sectional study.
AB  - OBJECTIVES: Korsakoff's syndrome (KS) is a chronic disorder caused by thiamine
      (vitamin B1) deficiency and alcoholism. The disorder is characterized by severe
      amnesia and often compared with dementia. The purpose of this study was to
      compare the quality of life between patients with KS and patients with dementia
      from the same nursing homes. DESIGN: Cross-sectional study design. SETTING: Three
      nursing homes in the Netherlands. PARTICIPANTS: Participants were 72 patients
      diagnosed with KS and 75 patients diagnosed with dementia through extensive
      neuropsychological evaluation and multidisciplinary diagnostics. MEASUREMENTS:
      Quality of life (QoL) was scored with the QUALIDEM scale. Multivariate linear
      regression analysis was used to compare QoL between patients with KS and patients
      with dementia, applying the covariates "age," "gender," and "nursing home."
      RESULTS: Of the 147 included patients, 72 (48.9%) were diagnosed with KS. Overall
      QoL was higher in KS. Patients with KS scored better than patients with dementia
      on the QUALIDEM subscales "Restless tense behavior," "Social relations," and
      "Having something to do." A trend toward a better score was found for the
      subscale "Positive affect"; a trend toward a lower score was found for "Feeling
      at home." CONCLUSIONS: KS is associated with profound differences in QoL compared
      with dementia. Patients with KS tend to have more social relationships and more
      positive emotions than patients with dementia. Furthermore, patients with
      dementia show more restless behavior than patients with KS; however, patients
      with KS tend to feel less at home in a nursing home than patients with dementia.
      Results suggest that both patients with dementia and patients with KS are in need
      of specialized nursing homes and care programs to accomplish their specific
      needs.

PMID- 22980998
TI  - The importance of foot care in older people with diabetes.

PMID- 22980999
TI  - Chronic kidney disease and its association with mortality and hospitalization in
      Chinese nursing home older residents: a 3-year prospective cohort study.
AB  - OBJECTIVE: To investigate chronic kidney disease (CKD) as a predictor of
      mortality and hospitalization in Chinese nursing homes older residents. DESIGN: A
      3-year prospective multicenter cohort study. SETTING: Nine nursing homes in Hong
      Kong. PARTICIPANTS: Nursing home older adults (812 total; 271 men and 571 women),
      mean age 86.0 +/- 7.6. MEASUREMENTS: Glomerular filtration rate (GFR) was
      estimated by the Modification of Diet in Renal Disease Study (Chinese-adjusted),
      and participants were stratified into different severity of renal impairment
      according to the modified version of Kidney Disease Outcomes Quality Initiative
      (K/DOQI): stage 1 CKD: GFR > 90 mL/min/1.73 m(2); stage 2 CKD: 60-89 mL/min/1.73
      m(2); stage 3A CKD: 45-59 mL/min/1.73 m(2); stage 3B CKD: 30-44 mL/min/1.73 m(2);
      stage 4/5: <30 mL/min/1.73 m(2). The outcome measures were the all-cause,
      infection-related, and cardiovascular-related mortality and hospitalizations.
      RESULTS: Older adults with stage 3B and stage 4/5 CKD had higher all-cause,
      infection-related, and cardiovascular-related mortality than those with earlier
      stages of CKD. After multivariate analysis, stage 3B and stage 4/5 CKD were
      independent predictors of all-cause mortality (stage 3B, hazard ratio [HR]: 1.62,
      95% CI: 1.12-2.33, P= .01; stage 4/5, HR: 2.00, 95% CI: 1.34-3.00, P= .001) and
      infection-related mortality (stage 3B, HR: 1.41, 95% CI: 1.08-2.30, P= .019;
      stage 4/5, HR: 1.91, 95% CI: 1.13-3.23, P= .016), but not cardiovascular-related
      mortalities. The all-cause, infection-related, and cardiovascular-related
      hospitalizations were significantly higher in older nursing home adults with
      stage 3B and stage 4/5 CKD. CONCLUSION: In Chinese nursing home older adults,
      stage 3B and stage 4/5 CKD are independent predictors of all-cause and infection
      related mortality. They also predict increased risks of all-cause, infection
      related, and cardiovascular-related hospitalizations.

PMID- 22981000
TI  - Biosynthesis of fomannoxin in the root rotting pathogen Heterobasidion
      occidentale.
AB  - Fomannoxin is a biologically active benzohydrofuran, which has been suggested to
      be involved in the pathogenicity of the root rotting fungus Heterobasidion
      annosum sensu lato. The biosynthesis of fomannoxin was investigated through an
      isotopic enrichment study utilizing [1-13C]glucose as metabolic tracer. 13C NMR
      spectroscopic analysis revealed the labeling pattern and showed that the isoprene
      building block originates from the mevalonic acid pathway, whereas the aromatic
      motif is formed via the shikimic acid route by elimination of pyruvate from
      chorismic acid. A natural product, 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde,
      was isolated and characterized, and was suggested to be a key intermediate in the
      biosynthesis of fomannoxin and related secondary metabolites previously
      identified from the H. annosum fungal species complex.

PMID- 22981001
TI  - Glucomannan and branched (1->3)(1->6) beta-glucan from the aposymbiotically grown
      Physcia kalbii mycobiont.
AB  - Cultures of the mycobiont Physcia kalbii were obtained from germinated ascospores
      and cultivated on Sabouraud-Sucrose-agar medium. Alkaline extraction of freeze
      dried mycelia provided a branched (1->3),(1->6)-beta-glucan and a glucomannan,
      whose chemical structure was determined by monosaccharide composition,
      methylation, controlled Smith degradation and NMR spectroscopic analysis. The
      beta-glucan had a (1->3)-linked beta-glucopyranosyl backbone, partially
      substituted (approx. 50% of the units) at O-6. The side chains were formed by 6-O
      (~82%) and 2,6-O-linked-beta-Glcp units, while the non-reducing ends were formed
      by beta-glucopyranosyl residues. The glucomannan had (1->6)-linked alpha-Manp
      units in the main chain, almost all being substituted at O-2 by alpha-Manp and
      alpha-Glcp units. This glucomannan could be a typical polysaccharide of lichens
      from the family Physciaceae.

PMID- 22981002
TI  - An untargeted metabolomic approach in the chemotaxonomic assessment of two Salvia
      species as a potential source of alpha-bisabolol.
AB  - alpha-Bisabolol is a commercially important aroma chemical currently obtained
      from the Candeia tree (Vanillosmopsis erythropappa). Continuous unsustainable
      harvesting of the Candeia tree has prompted the urgent need to identify
      alternative crops as a source of this commercially important sesquiterpene
      alcohol. A chemotaxonomic assessment of two Salvia species indigenous to South
      Africa is presented and recommended as a potential source of alpha-bisabolol. The
      essential oil obtained by hydrodistillation of the aerial parts was analysed by
      gas chromatography coupled to mass spectrometry (GC-MS) and mid-infrared
      spectroscopy (MIRS). Orthogonal projections to latent structures-discriminant
      analysis (OPLS-DA) were used for multivariate classification of the oils based on
      GC-MS and MIRS data. Partial least squares (PLS) calibration models were
      developed on the MIRS data for the quantification of alpha-bisabolol using GC-MS
      as the reference method. A clear distinction between Salvia stenophylla and
      Salvia runcinata oils was observed using OPLS-DA on both GC-MS and MIRS data. The
      MIR calibration model showed high coefficient of determination (R2 = 0.999) and
      low error of prediction (RMSEP=0.540%) for alpha-bisabolol content.

PMID- 22981003
TI  - The impact of comorbidities and complications on burn injury inpatient
      rehabilitation outcomes.
AB  - OBJECTIVE: To examine the impact of comorbidities and complications on burn
      inpatient rehabilitation facilities (IRF) outcomes. DESIGN: A retrospective cross
      sectional study. SETTING: Inpatient rehabilitation hospitals. PATIENTS: A total
      of 4572 patients with a primary diagnosis of burn injury from the Uniform Data
      System for Medical Rehabilitation database from 2002 to 2010. METHODS OR
      INTERVENTIONS: Regression analyses were used to determine whether 3 different
      comorbidity measures (Charlson Comorbidity Index, Elixhauser Comoribidity Index,
      Centers for Medicare and Medicaid Services Comorbidity Tiers) and 1 complication
      measure improved the predictive model (c-statistic) for each outcome measure.
      MAIN OUTCOME MEASUREMENTS: Community discharge, Functional Independence Measure
      (FIM) gain, length of stay efficiency, transfer to acute care within the first 3
      days of IRF stay, and transfer to acute care for all time periods. RESULTS: For
      all outcomes, there was no difference between the Standard Model and the models
      that include the comorbidity and complication variables as measured by the c
      statistic confidence intervals. CONCLUSIONS: Comorbidities and complications did
      not significantly affect burn IRF outcomes. Future research is needed to examine
      the impact of comorbidities and complications on outcomes of other IRF
      populations to better understand the implications for current and future health
      care policy.

PMID- 22981004
TI  - Subjective experiences of men with and without spinal cord injury: tolerability
      of the juvent and WAVE whole body vibration plates.
AB  - BACKGROUND: Device tolerability is an important determinant of subject adherence
      and intervention effectiveness. Although popular in rehabilitation settings, the
      tolerability of whole-body vibration (WBV) among patients with spinal cord injury
      (SCI) is unknown. OBJECTIVE: To assess feedback from SCI and non-SCI subjects on
      the usability of passive standing and WBV devices (Juvent [Juvent Medical,
      Somerset, NJ] and WAVE [WAVE Manufacturing, Windsor, Ontario, Canada]) using a
      priori specified knee postures, plate amplitudes, and frequencies. DESIGN: A
      matched groups design with repeated measures. SETTING: A tertiary SCI
      rehabilitation center. SUBJECTS: Eight men with chronic SCI (C4-L2, American
      Spinal Injury Association Impairment Scale A-D) and 10 men without SCI of similar
      height, weight, and body mass index. INTERVENTION: Subjects (N = 18; 8 with SCI)
      underwent intermittent WBV during passive standing (EasyStand 5000 [Altimate
      Medical, Morton, MN]) for 45 minutes using the optimized WAVE and Juvent plates.
      WBV parameters were sequentially altered every 2 minutes and included parameter
      combinations of (1) postures of 140 degrees , 160 degrees , and 180 degrees  knee
      extension (180 degrees  with Juvent only); (2) amplitudes of 0.7 mm and 1.1 mm
      (WAVE only); and (3) frequencies of 25 Hz, 35 Hz, and 45 Hz. Outcome assessments
      were completed at 4-minute intervals throughout WBV exposure. MAIN OUTCOME
      MEASURES: Qualitative, semistructured interviews were used to generate neutral,
      positive, and negative descriptors of the subjects' overall experience and device
      preference. RESULTS: SCI subjects reported a greater frequency of positive
      descriptors than non-SCI subjects during WBV, regardless of plate, posture,
      amplitude, or frequency, with the exception of 1 combination of parameters (WAVE
      plate at 140 degrees , 1.1 mm, and 25 Hz). Non-SCI subjects reported the highest
      frequency of negative effects with the WAVE plate at 160 degrees , 1.1 mm, 25 Hz,
      and 35 Hz. Non-SCI subjects preferred the Juvent, whereas SCI subjects preferred
      the WAVE plate. CONCLUSIONS: SCI and non-SCI subjects reported differing
      frequencies of positive and negative descriptors and indicated divergent device
      preferences. SCI subjects preferred the WAVE plate and vibration at high
      frequency. Future research will determine the therapeutic potential and adverse
      events associated with the device and WBV parameters tolerable for persons with
      SCI.

PMID- 22981005
TI  - Vibration platform training in women at risk for symptomatic knee osteoarthritis.
AB  - OBJECTIVE: To determine whether a platform exercise program with vibration is
      more effective than platform exercise alone for improving lower limb muscle
      strength and power in women ages 45 to 60 with risk factors for knee
      osteoarthritis (OA). DESIGN: Randomized, controlled study. SETTING: Academic
      center. PARTICIPANTS: A total of 48 women ages 45-60 years with risk factors for
      knee OA (a history of knee injury or surgery or body mass index >=25 kg/m(2)).
      INTERVENTIONS: Subjects were randomly assigned to a twice-weekly lower limb
      exercise program (quarter squat, posterolateral leg lifts, calf raises, step-ups,
      and lunges) on either a vertically vibrating platform (35 Hz, 2 mm) or a
      nonvibrating platform. MAIN OUTCOME MEASUREMENTS: Change in isokinetic quadriceps
      strength, leg press power, and stair climb power by 12 weeks. RESULTS: A total of
      39 of 48 enrolled participants completed the study (26 vibration and 13 control
      exercise). Nine participants discontinued the study after randomization mainly
      because of a lack of time. No intergroup differences in age, body mass index, or
      activity level existed. Isokinetic knee extensor strength did not significantly
      improve in either group. Leg press power improved by 92.0 +/- 69.7 W in the
      vibration group (P < .0001) and 58.2 +/- 96.2 W in the control group (P = .0499)
      but did not differ between groups (P = .2262). Stair climb power improved by 53.4
      +/- 64.7 W in the vibration group (P = .0004) and 55.7 +/- 83.3 W in the control
      group (P = .0329) but did not differ between groups (P = .9272). CONCLUSIONS:
      Whole body vibration platforms have been marketed for increasing strength and
      power. In this group of asymptomatic middle-aged women with risk factors for knee
      OA, the addition of vibration to a 12-week exercise program did not result in
      significantly greater improvement in lower limb strength or power than did
      participation in the exercise program without vibration.

PMID- 22981007
TI  - WITHDRAWN: Are there two different neural pathways for gender differences in
      autism spectrum disorders? - A pilot study.
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- 22981008
TI  - Apelin 13: a novel approach to enhance efficacy of hypoxic preconditioned
      mesenchymal stem cells for cell therapy of diabetes.
AB  - Recent studies have proposed cell therapy as an alternative therapeutic strategy
      for many disease states such as diabetes mellitus. Among different cell types
      mesenchymal stem cells (MSC) have attracted a significant attention based on
      their intriguing potentials. However MSC therapy is limited as a large portion of
      transplanted cells undergo apoptosis after transplantation. Therefore, proposing
      a strategy to overcome this obstacle may be of great value. Recent studies have
      shown that hypoxia preconditioning (HPC) may improve cell viability after
      transplantation. Both HPC and hyperglycemia are reported to exert effects by
      different levels of ROS overproduction. Overdose of ROS in this case would
      trigger the apoptosis and thereby decreased cell viability after transplantation.
      Apelin; the endogenous ligand for the previously orphaned G protein-coupled
      receptor APJ is shown to exert anti apoptotic effects On oxidative stress-induced
      apoptosis in MSCs via MAPK/ERK1/2 and PI3K/AKT signaling pathways. Accordingly it
      has been hypothesized that pretreatment of HPC-MSC(s) with apelin 13 would be an
      effective approach to modify and possibly enhance the efficacy of MSCs in cell
      therapy of diabetes.

PMID- 22981006
TI  - Indium 111 diethylenetriamine pentaacetic acid scintigraphy in the identification
      and management of intrathecal pump malfunction.
AB  - BACKGROUND: Intrathecal drug-delivery systems have become widely used tools in
      the management of refractory chronic pain and spasticity. Because increasing
      numbers of patients are using these systems, rehabilitation specialists
      frequently are the initial care providers who identify clinical signs and
      symptoms indicating possible complications relating to the implanted system.
      Identification of a pump malfunction often presents a diagnostic challenge.
      Distinguishing among progression of disease, new organic problems, and/or drug
      device complications is critical. The use of nuclear medicine indium 111
      diethylenetriamine pentaacetic acid (DTPA) studies represents a highly effective,
      straightforward, minimally invasive way to assess implant function and drug
      distribution. OBJECTIVE: To identify patients with suspected intrathecal pump
      malfunction and to determine whether the use of indium 111 DTPA is effective in
      identifying the source of failure. DESIGN: A retrospective review was performed
      from 2011 to 2012. SETTING: The study was performed at Georgia Health Sciences
      University. PATIENTS: The 23 selected patients had implanted devices for either
      spasticity or pain and were experiencing symptoms of a possible pump malfunction
      despite normal radiographic imaging. Twenty-four scintigraphic studies were
      performed, with malfunction documented in 19 patients. METHODS: A standard refill
      technique was used to inject 0.3 mL of indium 111 DTPA into the pump reservoir.
      Radionuclide images were reviewed at varying time points up to 48 hours after
      injection. The extent of radionuclide progression from the pump reservoir to the
      intrathecal space was evaluated. In cases in which a problem with the implant was
      identified, correlation with operative findings is described. RESULTS: Normal
      results of studies ultimately correlated with other clinical issues and confirmed
      an alternative etiology for the clinical changes noted. In studies with abnormal
      results, several patterns of failure were identified: restriction of the
      radionuclide to the pump reservoir, extravasations of tracer into the pump
      subcutaneous pocket, failure of the tracer to migrate from the subcutaneous
      catheter to the intrathecal space, and pooling of the tracer in the subcutaneous
      tissues. In all cases, surgical findings confirmed the suspected mechanism of
      malfunction as determined by the study. CONCLUSIONS: Indium 111 DTPA scintigraphy
      is a safe, straightforward way to identify and characterize clinical changes
      associated with intrathecal drug-delivery systems and to guide appropriate and
      clinical surgical management.

PMID- 22981009
TI  - Ultrasensitive electrochemical strategy for trace detection of APE-1 via triple
      signal amplification strategy.
AB  - A novel ultrasensitive electrochemical immunoassay for the determination of
      apurinic/apyrimidinic endonuclease (APE-1) using a three-step signal
      amplification process was reported in this work. The first-step signal
      amplification process was based on the labeled biotinylated alkaline phosphatase
      (bio-AP) on the nickel hexacyanoferrates nanoparticle-decorated Au nanochains (Ni
      AuNCs) toward the biocatalysis of ascorbic acid 2-phosphate (AA-P) to in-situ
      produce ascorbic acid (AA). Then the signal was further amplified by
      electrochemical oxidation of the in-situ-produced AA because of the catalysis of
      Ni-AuNCs. Finally, with the nanochain-modified streptavidin (SA), the
      stoichiometry of bio-AP could be increased through the specific and high affinity
      interaction of streptavidin-biotin. On the other hand, a kind of organic material
      (PTC-NH(2)), owing the amino-functionalized interface and unique electrochemical
      properties, as matrix for primary antibodies (Ab(1)) immobilization could lower
      the background current signal and enhance the amount of immobilized Ab(1). With a
      sandwich-type immunoreaction, the triple signal amplification greatly enhanced
      the sensitivity for the detection of APE-1. Under optimal conditions, the
      electrochemical immunosensor exhibited a linear range of 0.01-100 pg/mL with an
      extremely low detection limit of 3.9 fg/mL (signal/noise=3).

PMID- 22981010
TI  - Immunospot assay based on fluorescent nanoparticles for Dengue fever detection.
AB  - Dengue fever is one of the most neglected tropical diseases and of highest
      international public health importance, with 50 million cases worldwide every
      year. Early detection can decrease mortality rates from more than 20% to less
      than 1% and the relevant early diagnosis analyte is the viral non-structural
      glycoprotein, NS1. Currently, enzyme linked immunosorbent assay (ELISA) is the
      method of choice to detect NS1. However, this is a time consuming method,
      requiring 3-5h, and it is the bottleneck for routine of clinical analysis
      laboratory in epidemic periods, when hundreds of samples should be tested. Here
      we describe an easy method combining principles of fluorophore linked
      immunosorbent assay (FLISA) and enzyme linked immunospotting (ELISPOT). For
      detection, we used mouse anti-NS1 IgG labeled with fluorescent nanoparticles. The
      presented procedure needs only 4 MUL of serum samples and requires 45-60 min. The
      detection limit, 5.2 ng/mL, is comparable to ELISA tests. The comparison of 83
      samples with a commercial ELISA revealed a sensitivity of 81% and specificity of
      88%. The use of fluorescent nanoparticles provides a higher sensitivity than an
      assay using usual fluorescent dye molecules, besides avoiding bleaching effects.
      Based on the results, the proposed method provides fast, specific and sensitive
      results, and proves to be a suitable method for Dengue NS1 detection in
      impoverished regions or epidemic areas.

PMID- 22981011
TI  - Inferior vena cava clip migration: unusual cause of duodenal foreign body.
AB  - Before the development of the inferior vena cava (IVC) filter, various techniques
      of IVC interruption were described for the management of patients at high risk
      for thromboembolic events, and for whom anticoagulation was either inadequate or
      contraindicated. In this report, we describe the enteric migration of a Miles IVC
      clip, occurring 27 years after IVC interruption. This previously undescribed
      complication and the patient's prolonged follow-up period render this case of
      significant interest.

PMID- 22981013
TI  - Acute left-arm compartment syndrome due to cephalic arch stenosis in a dialysis
      patient.
AB  - Acute compartment syndrome of the upper limb due to dialysis access-related
      bleeding is a rare and severe complication of hemodialysis. In most reported
      cases, this complication is caused by an enlarging hematoma after puncture or
      perforation of a fistula in combination with the use of heparin. In this case
      report, we describe a 52-year-old woman presenting with venous hypertension and
      left-arm swelling that progressed suddenly on the fifth day of presentation to
      neurological deficits, cyanotic skin changes, and typical clinical symptoms of
      acute arm compartment syndrome. An angiographic scan confirmed a critical
      stenosis at the proximal cephalic-axillary venous junction, and balloon
      angioplasty successfully dilated the lesion. The arm swelling and other symptoms
      subsided dramatically within 3 days. This case represents a potentially different
      mechanism for the development of acute arm compartment syndrome in dialysis
      patients as well as a treatment strategy different from standard fasciotomy to
      reduce intracompartmental pressure.

PMID- 22981012
TI  - Endovascular repair of a left common carotid pseudoaneurysm associated with a
      jugular-carotid fistula after gunshot wound to the neck.
AB  - The management of traumatic injury of the common carotid artery has traditionally
      required a conventional surgical intervention, which is associated with a high
      mortality rate. Endovascular procedures might offer a less invasive alternative
      to treat these injuries, with a lower rate of mortality and morbidity. We report
      the case of a 30-year-old man who presented after penetrating injury due to a low
      velocity gunshot wound to the neck. Angiography demonstrated a high-flow
      arteriovenous fistula and large false aneurysm of the common carotid artery. A
      self-expanding covered stent was placed across the injured portion of the artery,
      resulting in thrombosis of the aneurysm and preservation of the parent artery,
      without any significant complication. Covered stent placement is an alternative
      approach to treating carotid artery pseudoaneurysms associated with a jugular
      carotid fistula.

PMID- 22981014
TI  - Endovascular treatment of ruptured abdominal aortic aneurysms with the Endurant
      device.
AB  - BACKGROUND: Endovascular treatment of ruptured aortic aneurysms is performed in
      many centers around the world. New endovascular stent-grafts may prove to improve
      results. We report our experience with the Endurant device. METHODS: From June
      2010 to November 2010, we treated five male patients (mean age: 75.8 years)
      suffering from ruptured abdominal aortic aneurysm with the Endurant device. The
      mean aneurysm diameter was 90.2 mm; the mean neck length was 13 mm; the mean
      proximal neck diameter was 27 mm; and the mean proximal angulation was 64 degrees
      . RESULTS: Technical success rate was 100%. In one patient, a proximal leak was
      diagnosed intraoperatively, and a proximal extension was successfully deployed.
      No secondary procedures were necessary and no open conversions required during
      the first admission. One patient required a proximal extension at 3 months for a
      type I endoleak. The 30-day mortality was 20%, and no further deaths occurred
      during the follow-up (mean duration: 15 months). CONCLUSION: New stent-grafts may
      ameliorate the prognosis of ruptured abdominal aortic aneurysms. Our experience
      with the Endurant device has shown promising results. To our knowledge, this is
      the first report of endovascular treatment of ruptured aortic aneurysms with this
      stent-graft.

PMID- 22981015
TI  - Outcomes after ulnar-basilic arteriovenous fistula formation.
AB  - BACKGROUND: The ulnar-basilic arteriovenous fistula (UBAVF) is rarely used owing
      to perceived problems with poor patency and prolonged maturation times. We report
      outcomes after UBAVF formation. METHODS: Patients who had a forearm UBAVF formed
      between October 1, 2002 and September 31, 2010 were identified from a
      prospectively maintained database. RESULTS: Fifty-two UBAVFs were formed in 48
      patients. The majority were male (77.1%), with a median (range) age of 69.5 (18
      86) years. Primary and secondary patencies at 1, 3, and 5 years were 43%, 13%,
      13%, and 54%, 18%, and 13%, respectively. Primary patencies were higher in those
      with previously functioning radiocephalic arteriovenous fistulas on the same arm
      (P = 0.03). Thirty-six percent of UBAVFs became functional, with a median (range)
      time to maturation of 100 (32-471) days. Nine UBAVFs (17.3%) required revision
      surgery. Complications were rare (7.7%), with only one case of steal syndrome.
      CONCLUSIONS: Although UBAVF patency and functionality rates are low, we believe
      that these are acceptable, given the low risk of complications and preservation
      of precious upper-arm venous capital. Maturation can be prolonged, but when the
      forearm cephalic vein is unusable, UBAVFs can provide an alternative to upper-arm
      fistulas, and should be utilized more widely, especially in those with previously
      functioning ipsilateral radiocephalic arteriovenous fistulas.

PMID- 22981016
TI  - Management of a challenging arteriovenous malformation of the scalp and orbit in
      a patient with polycystic kidney disease.
AB  - Arteriovenous malformations are notorious for their propensity to bleed,
      sometimes with fatal consequences. We describe an unusual case of a patient with
      polycystic kidney disease and with a large arteriovenous malformation involving
      the orbit and scalp who presented with multiple episodes of profuse bleeding from
      the upper eyelid and loss of vision in the corresponding eye.

PMID- 22981017
TI  - Prescribing patterns of antiplatelet agents are highly variable after lower
      extremity endovascular procedures.
AB  - BACKGROUND: The use of antiplatelet and antithrombotic agents after peripheral
      vascular interventions is a common clinical practice despite a lack of clear
      convincing evidence or accepted practice guidelines. The goal of this study was
      to assess surgeons' prescribing practices after endovascular procedures for lower
      extremity arterial occlusive disease. METHODS: Attendees at a national vascular
      meeting were asked to complete a voluntary survey indicating their prescribing
      practices of antiplatelet/antithrombotic agents for the following procedures:
      iliac bare-metal stent, iliac covered stent, infrainguinal balloon angioplasty,
      infrainguinal bare-metal stent, infrainguinal covered stent, infrainguinal
      atherectomy, and lower extremity cryoplasty. The respondents were given choices
      of aspirin (ASA) alone, clopidogrel alone, ASA/clopidogrel combined, warfarin
      alone, or ASA/clopidogrel/warfarin combined. They were also asked to indicate
      their preferred length of treatment for each medication or combination of
      medications for each procedure: 1, 3, 6, or 12 months. RESULTS: There were 51
      respondents (48 vascular surgeons and 3 vascular fellows) with an average of 11
      +/- 6.4 years of experience and practicing in a university hospital (48%),
      community hospital (44%), or combined university/Veterans A hospital (6%)
      setting. The majority of respondents (98%) prescribe an antiplatelet agent for
      patients with peripheral arterial disease using 81 mg of ASA preferentially. Most
      surgeons do not obtain genetic testing (i.e., cytochrome P450, polypeptide 19
      [CYP2C19] polymorphism) for antiplatelet effectiveness. The most common
      antiplatelet/antithrombotic medication of choice after lower extremity
      endoluminal therapy was a combination of ASA/clopidogrel. However, the duration
      of medical treatment was variable, with a 1- to 3-month course being the most
      common. The use of the ASA/clopidogrel combination increased with further distal
      endovascular treatment and the placement of stents versus angioplasty. In the
      vast majority of ASA-only responses, ASA was administered for at least 12 months
      if not recommended for life. Although the majority of surgeons would recommend
      dual antiplatelet therapy (52-77%), there was no consensus regarding the duration
      of treatment. CONCLUSIONS: The antiplatelet/antithrombotic prescribing practices
      of vascular surgeons after lower extremity endovascular procedures are highly
      variable. Multicenter randomized controlled trials are needed to define optimal
      treatment efficacy and define the much-needed practice guidelines.

PMID- 22981018
TI  - A longitudinal view of improved management strategies and outcomes after
      iatrogenic iliac artery rupture during endovascular aneurysm repair.
AB  - BACKGROUND: Intraoperative rupture of the iliac artery is a serious complication
      of endovascular aneurysm repair (EVAR), the outcomes of which have changed with
      increasing experience and improved endovascular tools over the past 2 decades.
      Over the past 15 years, the incidence and management of iliac rupture has changed
      as devices have improved and experience has grown. This study reviews our
      longitudinal experience with this complication. METHODS: All cases of iliac
      artery rupture during EVAR from 1997 through 2011 were reviewed for presentation,
      treatment strategies, and outcomes. RESULTS: Iliac artery rupture complicated 20
      (3%) of 707 EVARs performed. Sixteen (80%) common and four (20%) external iliac
      arteries were ruptured. Hypotension (systolic blood pressure: <90 mm Hg) was
      present in 11 (55%) cases. Five open bypasses were performed (25%), whereas 15
      were repaired using an endovascular approach (75%). All open repairs (100%) were
      associated with postoperative morbidity (one wound infection, four multiorgan
      system failure), whereas three of the 15 patients (23%) repaired endovascularly
      experienced postoperative morbidity (cerebrovascular accident, myocardial
      infarction, line infection). There were no intraoperative deaths. There were four
      (20%) early deaths in the intensive care unit (<3 days postoperatively), all of
      which were associated with resection of bilateral hypogastric arteries and were
      due to complications of pelvic ischemia and/or multiorgan system failure.
      CONCLUSIONS: Iliac artery rupture remains relatively uncommon but can carry a
      high morbidity and mortality. As device technology, imaging quality for
      preoperative planning, and experience level have improved, iliac rupture has
      become less common, and outcomes in the setting of iliac rupture have
      significantly improved. Endoluminal management has evolved as the primary
      treatment strategy. Resection of both hypogastric arteries is associated with
      mortality from pelvic ischemia, a likely indicator of systemic disease.

PMID- 22981019
TI  - Short-term outcomes of the C3 excluder for patients with abdominal aortic
      aneurysms and unfavorable proximal aortic seal zones.
AB  - BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR) in patients with
      unfavorable proximal seal zones remains challenging. The purpose of this study
      was to identify the incidence of proximal extension cuff usage for type I
      endoleaks in patients with abdominal aortic aneurysms and unfavorable necks
      treated with the C3 Excluder repositionable endoprosthesis compared with the
      traditional Excluder stent-graft. METHODS: This is a retrospective review of
      patients undergoing EVAR with unfavorable neck anatomy from January 2010 to
      October 2011 using the Excluder endoprosthesis on the traditional deployment
      system or the C3 repositionable system. Seventy-seven patients were treated with
      the Excluder device, with 44 (57%) having unfavorable neck anatomy defined as
      proximal aortic neck length of <15 mm, neck diameter of >28 mm, neck angulation
      of >60 degrees , circumferential thrombus of >50% or calcification at the
      proximal seal zone, or a "reverse taper" on computed tomographic angiography. Of
      the 44 patients with unfavorable neck anatomy, 24 patients received the C3
      Excluder and 20 received the traditional Excluder. RESULTS: The groups'
      comorbidities, aneurysm characteristics, and high-risk neck criteria were
      comparable. Initial success was 100% in both groups. Sixteen of the 44 patients
      (36%) with high-risk neck criteria required proximal extension cuffs for type I
      endoleaks, with 3 of the 24 patients (13%) in the C3 group compared with 13 of
      the 20 patients (65%) in the traditional Excluder group requiring proximal
      extension (P = 0.0005). Operative variables between the two groups were similar.
      At mean follow-up of 2 months (range: 1-6 months), there were no type I endoleaks
      or renal artery occlusion, and sac size regression was similar. CONCLUSIONS: The
      C3 Excluder endoprosthesis significantly reduces the need for proximal extension
      cuffs in patients with unfavorable aortic neck anatomy compared with the
      traditional Excluder with identical short-term clinical outcomes. Repositionable
      grafts could increase the number of patients who can effectively be treated with
      EVAR.

PMID- 22981020
TI  - Risk factors for early failure after peripheral endovascular intervention:
      application of a reliability engineering approach.
AB  - BACKGROUND: We apply an innovative and novel analytic approach, based on
      reliability engineering (RE) principles frequently used to characterize the
      behavior of manufactured products, to examine outcomes after peripheral
      endovascular intervention. We hypothesized that this would allow for improved
      prediction of outcome after peripheral endovascular intervention, specifically
      with regard to identification of risk factors for early failure. METHODS:
      Patients undergoing infrainguinal endovascular intervention for chronic lower
      extremity ischemia from 2005 to 2010 were identified in a prospectively
      maintained database. The primary outcome of failure was defined as patency loss
      detected by duplex ultrasonography, with or without clinical failure. Analysis
      included univariate and multivariate Cox regression models, as well as RE-based
      analysis including product life-cycle models and Weibull failure plots. Early
      failures were distinguished using the RE principle of "basic rating life," and
      multivariate models identified independent risk factors for early failure.
      RESULTS: From 2005 to 2010, 434 primary endovascular peripheral interventions
      were performed for claudication (51.8%), rest pain (16.8%), or tissue loss
      (31.3%). Fifty-five percent of patients were aged >=75 years; 57% were men.
      Failure was noted after 159 (36.6%) interventions during a mean follow-up of 18
      months (range, 0-71 months). Using multivariate (Cox) regression analysis, rest
      pain and tissue loss were independent predictors of patency loss, with hazard
      ratios of 2.5 (95% confidence interval, 1.6-4.1; P < 0.001) and 3.2 (95%
      confidence interval, 2.0-5.2, P < 0.001), respectively. The distribution of
      failure times for both claudication and critical limb ischemia fit distinct
      Weibull plots, with different characteristics: interventions for claudication
      demonstrated an increasing failure rate (beta = 1.22, theta = 13.46, mean time to
      failure = 12.603 months, index of fit = 0.99037, R(2) = 0.98084), whereas
      interventions for critical limb ischemia demonstrated a decreasing failure rate,
      suggesting the predominance of early failures (beta = 0.7395, theta = 6.8, mean
      time to failure = 8.2, index of fit = 0.99391, R(2) = 0.98786). By 3.1 months,
      10% of interventions failed. This point (90% reliability) was identified as the
      basic rating life. Using multivariate analysis of failure data, independent
      predictors of early failure (before 3.1 months) included tissue loss, long lesion
      length, chronic total occlusions, heart failure, and end-stage renal disease.
      CONCLUSIONS: Application of a RE framework to the assessment of clinical outcomes
      after peripheral interventions is feasible, and potentially more informative than
      traditional techniques. Conceptualization of interventions as "products" permits
      application of product life-cycle models that allow for empiric definition of
      "early failure" may facilitate comparative effectiveness analysis and enable the
      development of individualized surveillance programs after endovascular
      interventions.

PMID- 22981021
TI  - Quality of life among patients with bipolar disorder in primary care versus
      community mental health settings.
AB  - INTRODUCTION: Bipolar disorder is associated with functional impairment across a
      number of domains, including health-related quality of life (HRQOL). Many
      patients are treated exclusively in primary care (PC) settings, yet little is
      known how HRQOL outcomes compare between PC and community mental health (CMH)
      settings. This study aimed to explore the correlates of HRQOL across treatment
      settings using baseline data from a multisite, randomized controlled trial for
      adults with bipolar disorder. METHODS: HRQOL was measured using the SF-12
      physical (PCS) and mental (MCS) composite scale scores. Independent sample t
      tests were calculated to compare differences in HRQOL between settings.
      Multivariate regression models then examined the effect of treatment setting on
      HRQOL, adjusting for covariate demographic factors, mood symptoms (Internal State
      Scale), hazardous drinking (AUDIT-C), and substance abuse. RESULTS: A total of
      384 enrolled participants completed baseline surveys. MCS and PCS scores
      reflected similar impairment in HRQOL across PC and CMH settings (p=0.98 and
      p=0.49, respectively). Depressive symptoms were associated with lower MCS scores
      (B=-0.68, p<0.001) while arthritis/chronic pain was strongly related to lower PCS
      scores (B=-5.23, p<0.001). LIMITATIONS: This study lacked a formal diagnostic
      interview, relied on cross-sectional self-report, and sampled from a small number
      of sites in two states. DISCUSSION: Participants reported similar impairments in
      both mental and physical HRQOL in PC and CMH treatment settings, emphasizing the
      need for integrated care for patients with bipolar disorder regardless of where
      they present for treatment.

PMID- 22981022
TI  - [From comparative effectiveness research to patient-centered outcomes research].

PMID- 22981023
TI  - [Different name, same meaning? Comparative effectiveness research and patient
      centered outcomes research in the USA].
AB  - In 2009 the Congress of the USA commissioned a program on "Comparative
      Effectiveness Research" (CER) for two years. The program was funded with 1.1
      billion USD and aims at projects that are directly relevant for the care of
      patients, investigate research questions and populations where research gaps are
      considerable, and which compare at least two interventions. Three years later it
      seems that in the USA CER has been replaced by "Patient-Centered Outcomes
      Research" (PCOR). This article summarizes the conceptual and empirical
      development of CER since 2009 and looks at the similarities and differences
      between CER and PCOR.

PMID- 22981024
TI  - [Palliative care: an example of Comparative Effectiveness Research?].
AB  - Comparative Effectiveness Research (CER) seeks to establish treatment objectives
      and concepts striving to achieve patient relevant progress in therapy on the
      basis of published evidence. Using the example of palliative medicine and
      palliative care, respectively, it will be demonstrated that these two are under
      researched areas of care. In addition, it will become clear that the success of
      this interdisciplinary treatment concept for the seriously ill must be weighed in
      the light of traditional clinical research - far beyond the cancer diagnosis. The
      current distinction between curative and palliative research and care urgently
      needs to be reconsidered.

PMID- 22981025
TI  - [Comment: Hurdles for comparative effectiveness research in Germany].

PMID- 22981026
TI  - [The preliminary draft of the methodology report by the Patient-Centered Outcomes
      Research Institute].
AB  - There is a mismatch between results of clinical trials and the needs of patients.
      The Patient-Centered Outcomes Research Institute (PCORI) in the US will
      commission research that supports patients and providers of care to make informed
      decisions. The preliminary draft of a methodology report presented by PCORI
      contains methodological standards which researchers will have to take into
      account when applying for funds from PCORI. An innovative instrument, the
      "Translation Tool" has been introduced to judge the best match between a specific
      research question and the corresponding methods. The "Translation Tool"
      structures the necessary trade-offs (e.g. between validity, patient-centered
      endpoints, timeliness, and resources) in a transparent manner. This article
      summarizes the development, structure and content of the methodology report. (As
      supplied by publisher).

PMID- 22981027
TI  - [A standardised German translation of the STAndards for Reporting of Diagnostic
      accuracy studies (STARD statement)*: Methodological aspects].
AB  - BACKGROUND: In order to be comprehensible and comparable scientific data should
      be reported according to a certain standard. One example is the 'STAndards for
      Reporting of Diagnostic Accuracy (STARD) Statement', a 25-item checklist for the
      appropriate conduct and reporting of diagnostic studies. Usually such scientific
      standards are published in English. The International Society for
      Pharmacoeconomics and Outcome Research (ISPOR) has developed guidelines for the
      translation and cultural adaptation of written medical instruments. The aim was
      to apply these ISPOR criteria to the German translation of the STARD Statement in
      order to allow for authorisation to be conferred by the original authors.
      METHODS: In cooperation with the original authors the STARD statement was
      translated according to the ISPOR steps: (1) Preparation, (2) Forward
      Translation, (3) Reconciliation, (4) Back Translation, (5) Back Translation
      Review, (6) Harmonisation, (7) Cognitive Debriefing, which evaluated
      comprehensiveness and linguistic style with marks from 1 (very good) to 6
      (insufficient), and (8) Review of Cognitive Debriefing Results and Finalisation.
      RESULTS: Die ISPOR criteria applied reasonably to the translation process, which
      required the work input and energy of four scientists and one professional
      translator and 177 accumulated working hours. The cognitive debriefing resulted
      in average grades 1.62+/-0.33 and 1.72+/-0.39 for comprehensiveness and
      linguistic style, respectively. Finally, the German STARD version was authorised
      by the original authors. CONCLUSION: Die ISPOR guidelines seem to be a suitable
      means to facilitate the structured adaptation of defined criteria for the
      reporting of studies, such as the STARD statement, to other languages.

PMID- 22981028
TI  - [Information on legal issues in health technologies: methodological proposal to
      identify them in a systematic and comprehensible manner].
AB  - BACKGROUND: Rules and regulations form the framework of Health Technology
      Assessments. Legal issues are directly associated with the technology (as
      patents/licenses) or to the patients and their basic rights (as autonomy). In
      order to identify the regulations of interest as well as the relevant
      publications in a systematic and transparent way a specific methodological
      approach is required. In the absence of adapted methods, our objective was to
      develop a methodological approach to the systematic retrieval of information on
      legal issues. METHODS:  RESULTS: No publications on adapted methods could be
      identified. We therefore developed a procedure following the workflow of
      information retrieval for effectiveness assessments. This workflow consists of 8
      steps: 0. pre-search: identification of the relevant rules, regulations and
      patient-related issues, 1. translation of the search question, 2. concept
      building, 3. identification of synonyms, 4. selection of relevant information
      sources, 5. design of the search strategies, 6. execution and quality check, 7.
      saving the results and reporting. CONCLUSIONS: There are numerous publications on
      legal issues associated with health technologies. Specifically adapted procedures
      are qualified to identify them in a systematic and transparent manner using the
      appropriate sensitivity and precision. A wider application seems to be reasonable
      in order to further test its practicality against more topics and to modify the
      proposed method if indicated.

PMID- 22981029
TI  - [Interprofessional education for patient-centred practice: development of outcome
      focused competencies for a Bachelor Programme Interprofessional Health Care].
AB  - OBJECTIVES: Health care systems in Germany and around the world are faced with
      demographic change and the need of providing health services in increasingly
      complex health care surroundings. A highly qualified workforce is needed to face
      the challenges ahead and to coordinate health care. In addition, there is
      evidence that interprofessional education strengthens interprofessional
      collaboration which can lead to improved health outcomes. The University of
      Heidelberg, Medical Faculty, decided to develop a bachelor programme integrating
      specific health professions and interprofessional qualifications into the
      curriculum. The manuscript describes the identification process of the outcome
      focused competencies for this bachelor degree. METHODS: The six-step curriculum
      model by Kern et al. was applied. An expert panel identified major tasks and
      health care fields for which the students should be qualified for. These results
      were transferred into a questionnaire and distributed among targeted learners as
      well as practitioners, experts and employers in different health care fields for
      relevance ratings. Also, individuals were interviewed to receive additional
      information and to generate further ideas. RESULTS: Thirteen different practice
      fields, five tasks and thirteen topics common to all health care professions were
      collected. The subsequent survey comprising 66 items was completed by 139
      targeted learners as well as 82 practitioners and experts. All identified
      practice fields were rated as relevant for future professional life. Top ratings
      were "supervising procedures" (targeted learners) and "interprofessional
      communication and coordination" (practitioners, experts and employers). The
      results were discussed and consented in the expert panel and learner
      outcomes/objectives were categorized according to the CanMED roles. DISCUSSION: A
      thorough needs assessment was performed setting the foundation for the further
      development of the curriculum. The identified competencies are in line with the
      five core competencies defined by the WHO which are necessary for
      interprofessional collaboration: patient-centred care, partnering, quality
      improvement, information and communication technology, and public health
      perspective. The application of the CanMED framework proved to be suitable. It
      may be used as common terminology to help define interfaces with curricula of
      other health professions. The interprofessional development of the bachelor
      programme fostered a deeper understanding between health professionals and can
      therefore be regarded as a first step in improving interprofessional
      collaboration.

PMID- 22981030
TI  - [IGeL - a questionable debate].

PMID- 22981031
TI  - Effect of a treatment strategy consisting of pravastatin, vitamin E, and
      homocysteine lowering on arterial compliance and distensibility in patients with
      mild-to-moderate chronic kidney disease.
AB  - BACKGROUND: Arterial stiffness is increased in chronic kidney disease (CKD).
      Intervention studies aimed at reduction of arterial stiffness in dialysis
      patients have been disappointing. We therefore investigated the effect of
      pravastatin, vitamin E, and homocysteine lowering on arterial compliance and
      distensibility coefficients in mild-to-moderate CKD. METHODS: This is a sub-study
      of the ATIC study, a randomized, double-blind trial in 93 CKD patients. The
      treatment group received pravastatin to which vitamin E supplementation was added
      after 6 months and homocysteine lowering therapy after another 6 months.
      Measurement of the distensibility coefficient (DC) and the compliance coefficient
      (CC) of the common carotid (CCA), femoral (FA) and brachial artery (BA) was
      performed at 0, 6, 12, 18 months. Young's elastic modulus (YEM) was measured in
      the common carotid artery. RESULTS: After 18 months, CCA-DC increased from mean
      (SD) 15.15 (6.67) to 16.52 (6.37) * 10-3kPa-1 in the treatment and decreased from
      18.44 (8.19) to 16.26 (7.35) in the placebo group (p = 0.057). CCA-CC increased
      from 0.64 (0.24) to 0.71 (0.26) mm2kPa-1 in the treatment and decreased from 0.77
      (0.28) to 0.69 (0.25) in the placebo group (p < 0.0001). FA-DC had increased from
      6.64 (3.45) to 11.46 (6.83) in the treatment group, and from 6.46 (2.85) to 7.08
      (2.73) in the placebo group (p = 0.0001). FA-CC had increased from 0.46 (0.24) to
      0.74 (0.44) in the treatment group, and from 0.48 (0.27) to 0.53 (0.21) in the
      placebo group (p = 0.008). BA-DC and CC, and CCA YEM were not significantly
      different between the groups. CONCLUSION: In patients with mild-to-moderate CKD,
      18 months of treatment consisting of pravastatin, vitamin E and homocysteine
      lowering resulted in significant improvement of compliance and distensibility in
      CCA and FA. Since pravastatin was used throughout the observation period, it
      remains unclear whether the beneficial effects are attributable solely to the
      ongoing effect of pravastatin treatment, or if the additional interventions
      further slowed the progression of vascular stiffness. Therefore, larger studies
      with a longer period of follow-up observing the separate effects are needed.

PMID- 22981032
TI  - Spontaneous bilateral renal pelvis thrombus formation presenting as anuric acute
      renal failure.
AB  - A 59-year-old woman was admitted to the internal medicine service after
      presenting to the emergency department with complaints of abdominal pain and
      hematuria. Upon further evaluation, the patient was found to be significantly
      coagulopathic secondary to the intentional ingestion of brodifacoum, the active
      ingredient in D-Con rat poison, in an attempt to commit suicide. The patient was
      treated and discharged only to return several days later with new pain and the
      inability to urinate. She was found to be in acute renal failure and renal
      ultrasonography revealed bilateral ureteral and renal pelvis thrombus leading to
      acute obstructive nephropathy. She was taken emergently to the operating room for
      placement of bilateral ureteral stents which resulted in decompression of her
      collecting system and resolution of her renal failure.

PMID- 22981033
TI  - Fanconi syndrome and chronic kidney disease in paroxysmal nocturnal
      hemoglobinuria: effect of eculizumab therapy.
AB  - The association of Fanconi syndrome (FS) and chronic kidney disease (CKD) has
      been rarely described during the course of paroxysmal nocturnal hemoglobinuria
      (PNH). We report 2 patients with PNH and CKD associated with proximal tubule
      dysfunction, which manifested as full-blown FS in one case. In both patients,
      abnormal iron load within the kidneys was demonstrated by magnetic resonance
      imaging, which correlated with diffuse and numerous hemosiderin inclusions within
      proximal tubular cells. After 12 months, eculizumab treatment resulted in
      significant decrease in the kidney iron load in both cases. Glomerular filtration
      rate improved in one case and was stabilized in the other, in whom pretreatment
      kidney biopsy had shown severe extensive interstitial fibrosis. However, symptoms
      of proximal tubular dysfunction persisted in both patients. These data suggest
      that hemosiderin deposition in proximal tubules is probably an important
      mechanism involved in the development of FS, an under recognized and early
      manifestation of CKD in PNH. Prolonged treatment with eculizumab may improve long
      term renal function in PNH patients with CKD.

PMID- 22981034
TI  - Elevated serum creatinine in a kidney transplant recipient: unusual suspect.
AB  - We report a rare form of transplant renal artery stenosis discovered 3 months
      after transplantation. Our patient had mechanical renal artery "kinking", which
      responded to balloon angioplasty. Doppler ultrasound, followed by an arteriogram
      confirmed the diagnosis. This case demonstrates that transplant renal artery
      "kinking" stenosis,though rare, can cause graft dysfunction and worsening
      hypertension in kidney transplant recipients.

PMID- 22981035
TI  - Newly developed hypertension due to juxtaglomerular cell tumor in pregnancy.
AB  - An unusual case of juxtaglomerular cell tumor (JCT) is presented. A 29-year-old
      woman visited our hospital for the management of incidentally detected renal mass
      due to newly developed hypertension in the 20th week of pregnancy. Laboratory
      studies showed increased basal plasma renin activity and hypokalemia but serum
      aldosterone level was normal. Abdominal computed tomography scan showed about 2.4
      cm sized multicystic mass in the right kidney. Nephron-sparing surgery was
      performed with excellent results. On histological examination, the tumor
      exhibited a structure typical feature of JCT. A few days later the patient's
      blood pressure had been normalized.

PMID- 22981036
TI  - Thomsen-Friedenreich antigen exposure as a cause of Streptococcus pyogenes
      associated hemolytic-uremic syndrome.
AB  - Infection with Streptococcus pyogenes, a Group A beta-hemolytic streptococcus
      (GAS), is a rare cause of hemolyticuremic syndrome (HUS). Invasive infections
      with Streptococcus pneumoniae that produce neuraminidase are a well-recognized
      cause of HUS without diarrhea. The Thomsen- Friedenreich antigen (T antigen)
      plays a role in the pathophysiology of pneumococcal HUS. We describe the case of
      a 3-year-old boy with GAS-associated HUS and show how T-antigen exposure was
      implicated in this case. He had no diarrhea and cultures for blood, urine, and
      stool were negative. The urinary pneumococcal antigen was negative; his direct
      Coombs test was positive. Glomerular capillary loops, tubular epithelium on his
      renal biopsy specimen, and red blood cells in his blood smear showed positive
      fluorescence with anti-T lectin. Although the pathogenesis of GAS-associated HUS
      is not well understood, T-antigen exposure may be implicated in some cases with
      GAS-associated HUS.

PMID- 22981037
TI  - [Care and intervention strategies for older people in social exclusion situations
      in publicly funded residential centres].

PMID- 22981038
TI  - Novel approach for posttraumatic panarthritis of the wrist using a pyrocarbon
      interposition arthroplasty (Amandys((r))): Preliminary series of 11 patients.
AB  - OBJECTIVES: In case of posttraumatic radiocarpal destruction, failure of first
      row carpectomy or partial arthrodesis, there are two options, total prosthesis of
      the wrist or panarthrodesis. Both solutions have limitations. The aim of our
      study was to evaluate an alternative therapy: interposition arthroplasty with
      pyrocarbon implant at follow-up of minimum 6months. METHODS: This is a
      retrospective monocentric study with clinical and radiological evaluation. This
      study includes 11 patients with a mean age of 55.2years. There were four failures
      of first row carpectomy, a failure of partial arthrodesis, a case of post
      infection osteoarthritis, four cases of stage IV SNAC wrists and one siliconitis
      after a scaphoid implant. RESULTS: At the average follow-up of 11 months, pain
      was improved in nine cases. The average flexion was 36.5 degrees  and average
      extension, 35 degrees . The average strength was 8.3kg. Two implant dislocations
      occurred, only one required second look surgery for implant replacement. However,
      in this patient, pain remained severe and required panarthrodesis. In another
      patient, a second panarthrodesis was performed for resistant pain. CONCLUSIONS:
      The interposition arthroplasty with pyrocarbon seems to give encouraging results
      as an alternative therapy. It gives satisfactory mobility, pain relief, but
      moderate strength. It has the advantages of a simple technique and does not
      preclude manual activities. A long-term validation is, of course, necessary.

PMID- 22981039
TI  - [Abdominal pain, pulsatile mass and leukocytosis in a patient previously
      suffering from diarrhoea].

PMID- 22981041
TI  - Usefulness of rickettsial PCR assays for the molecular diagnosis of human
      rickettsioses.
AB  - BACKGROUND: The effectiveness of PCR methods to amplify rickettsiae from clinical
      samples has still not been evaluated. Our aim was to determine the sensitivity
      and usefulness for Rickettsia species identification by PCR methods, targeting
      16S rDNA, htrA, gltA, ompA, and ompB genes for molecular diagnosis of
      rickettsioses. METHODS: A total of 72 clinical samples (EDTA-blood, skin biopsies
      and ticks) taken from 52 patients in the early phase of the illness with PCR
      confirmed rickettsioses were included. Single [16S rDNA, gltA (5' end), and htrA
      genes] and sequential (nested or semi-nested) PCR assays [ompB, gltA (central
      region) and ompA genes] were performed. RESULTS: For single-stage PCR assays, the
      greatest sensitivity (33.3%) was obtained using the gltA (5' end), while for
      sequential assays, the most sensitive results were obtained using the ompB assay
      (83.3%). The highest sensitivity (100%) was achieved using the three sequential
      PCRs. The ompA PCR method was the most reliable for identifying Rickettsia
      species, according to clinical features. CONCLUSIONS: PCR-based amplification
      methods are useful rickettsial diagnostic tools in the early phase of the
      illness. The three sequential PCR assays here investigated (ompB, gltA and ompA)
      appear to be useful tools for molecular diagnosis of rickettsioses. ompB PCR
      assay is effective for primary screening, since it detects a high percentage of
      positive samples. ompA assay is the most useful method to identify a Rickettsia
      species in human pathology. Nevertheless, epidemiology, clinical symptoms and the
      vector involved in the infection have to be taken into account for the diagnosis
      of rickettsioses.

PMID- 22981040
TI  - [Burkholderia bacteraemia in an immunocompetent girl with fever of unknown
      origin].

PMID- 22981042
TI  - Middle Pleistocene human facial morphology in an evolutionary and developmental
      context.
AB  - Neanderthals and modern humans exhibit distinct facial architectures. The
      patterning of facial morphology of their predecessors, the Middle Pleistocene
      humans, is more mosaic showing a mix of archaic and modern morphologies.
      Significant changes in facial size and robusticity occurred throughout
      Pleistocene human evolution, resulting in temporal trends in both facial
      reduction and enlargement. However, the allometric patterning in facial
      morphology in archaic humans is not well understood. This study explores temporal
      trends in facial morphology in order to gain a clearer understanding of the
      polarity of features, and describes the allometric patterning of facial shape.
      The modern human sample comprises cross-sectional growth series of four
      morphologically distinct human populations. The fossil sample covers specimens
      from the Middle Pleistocene to the Upper Paleolithic. We digitized landmarks and
      semilandmarks on surface and computed tomography scans and analyzed the
      Procrustes shape coordinates. Principal component analyses were performed, and
      Procrustes distances were used to identify phenetic similarities between fossil
      hominins. In order to explore the influence of size on facial features,
      allometric trajectories were calculated for fossil and modern human groups, and
      developmental simulations were performed. We show that facial features can be
      used to separate Pleistocene humans into temporal clusters. The distinctly modern
      human pattern of facial morphology is already present around 170 ka. Species- and
      population-specific facial features develop before two years of age, and several
      of the large-scale facial differences between Neanderthals and Middle Pleistocene
      humans are due to scaling along a shared allometric trajectory. These features
      include aspects of the frontal bone, browridge morphology, nasal aperture size
      and facial prognathism. Infraorbital surface topography and orientation of the
      midface in the European Middle Pleistocene hominins is intermediate between the
      African Middle Pleistocene and Neanderthal condition. This could suggest that the
      European Middle Pleistocene hominins display incipient Neanderthal features.

PMID- 22981043
TI  - Critical review of research literature on climate-driven malaria epidemics in sub
      Saharan Africa.
AB  - OBJECTIVES: To obtain a better understanding of existing research evidence
      towards the development of climate-driven malaria early warning systems (MEWS)
      through critical review of published literature in order to identify challenges
      and opportunities for future research. STUDY DESIGN: Literature review. METHODS:
      A comprehensive search of English literature published between 1990 and 2009 was
      conducted using the electronic bibliographic database, PubMed. Only studies that
      explored the associations between environmental and meteorological covariates, El
      Nino Southern Oscillation (ENSO) and malaria as the basis for developing, testing
      or implementing MEWS were considered. RESULTS: In total, 35 relevant studies
      revealed that the development of functional climate-based MEWS remains a
      challenge, partly due to the complex web of causality and partly due to the use
      of imprecise malaria data, spatially and temporally varying covariate data, and
      different analytical approaches with divergent underlying assumptions.
      Nevertheless, high resolution spatial and temporal data, innovative analytical
      tools, and new and automated approaches for early warning and the development of
      operational MEWS. CONCLUSIONS: Future research should exploit these opportunities
      and incorporate the various aspects of MEWS for functional epidemic forecasting
      systems to be realized.

PMID- 22981044
TI  - The importance of understanding epidemiology in order to inform financial
      decisions: a lesson from the Scottish Home Oxygen Service.
AB  - OBJECTIVES: To ensure that decisions on the future planning of the Scottish Home
      Oxygen Service reflect population needs by examining the epidemiology of the main
      conditions that require home oxygen therapy and trends in their management. STUDY
      DESIGN: Analysis of routinely available vital event and health service data
      supplemented by published literature. Use of linked data to provide person-based
      analyses. METHODS: Consideration of trends in key risk factors, disease
      incidence, prevalence and mortality for chronic neonatal lung disease, cystic
      fibrosis, chronic interstitial lung disease in adults and chronic obstructive
      pulmonary disease. Examination of trends in management of these conditions
      including hospital admissions, length of stay and re-admissions. RESULTS: The
      prevalence of all the conditions studied has increased in Scotland over recent
      years due to a combination of increased incidence, increased survival, more
      active case finding and demographic changes. There have been changes in
      management with trends towards shorter hospital stays. CONCLUSIONS: The clinical
      need for home oxygen therapy is likely to continue to increase over the next 10
      20 years. It will encompass all age groups and a complex range of conditions.
      Public health needs to be proactive in providing relevant needs assessment
      information to ensure that planning within financial constraints is appropriately
      informed on population needs.

PMID- 22981046
TI  - Mental health literacy, stigma, and early intervention.

PMID- 22981045
TI  - Pro-inflammatory cytokine profile of critically ill septic patients following
      therapeutic plasma exchange.
AB  - Severe sepsis involves a generalized inflammatory response, mediated by a number
      of various cytokines and factors. Plasma exchange (PE) has been proposed as a
      therapeutic approach to improve survival of patients with severe sepsis and
      septic shock. The theory is that removing harmful excessive endogenous
      inflammatory mediators is beneficial. Upon establishment of a diagnosis of severe
      sepsis, twelve patients received PE plus conventional sepsis treatment.
      Interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF)-alpha were assayed
      before and after each session of PE. RESULTS: There were no significant changes
      in cytokine plasma levels after each PE session compared to pre-procedure levels.
      Among measured pro-inflammatory cytokines, only the plasma levels of IL-6 before
      the 2nd and 3rd PE sessions were lower than baseline levels (p=0.011 and p=0.012,
      respectively). All patients tolerated PE therapy well without any adverse effects
      or homodynamic instability. The results of this study showed that PE does not
      have a direct and rapid effect on plasma level of TNF-alpha, IL-1beta and IL-6.

PMID- 22981047
TI  - Should pathological gambling be considered an addictive disorder?
AB  - Although pathological gambling is a relatively common disorder, there are only
      limited data available about the validity of its diagnosis as an impulse control
      disorder. Interestingly, there is no single conceptual widely accepted model that
      adequately accounts for the multiple biological, psychological and ecological
      variables contributing to the development of pathological gambling. In this
      paper, the authors demonstrate aspects of addictive behavior of pathological
      gambling. It is suggested that despite conceptual difficulties associated with
      the variable of self-control, contemporary research into the addictive behavior
      of gambling has clearly demonstrated its closeness to addictions as compared to
      impulse control disorders.

PMID- 22981048
TI  - A study of psychiatric morbidity during second trimester of pregnancy subsequent
      to abortion in the previous pregnancy.
AB  - INTRODUCTION: Pregnancy plays a unique role in the transformation of women
      towards completeness. For those women who have had a previous unsuccessful
      outcome, pregnancy may bring a lot of inevitable negative emotions. We studied
      psychiatric morbidity during second trimester of pregnancy subsequent to abortion
      in the previous pregnancy. METHODS: The study was carried out in Dayanand Medical
      College and Hospital, Ludhiana, India. A total of 120 patients were divided into
      4 groups depending on their pregnancy status. All the groups were compared with
      each other regarding their psychiatric morbidities, which were measured using
      various rating scales such as Hamilton Depression rating scale, Hamilton Anxiety
      Rating Scale, State Trait Anxiety Inventory, Presumptive Stressful Life events
      Scale, and Brief Psychotic Rating Scale. RESULTS: We found that subjects with
      history of previous abortion, whether single or more had significantly higher
      mean depression and anxiety score than primigravida or subjects with history of
      previous successful pregnancy; depression and anxiety scores decreased with
      increase in time gap between abortion and current pregnancy. High anxiety was
      found in 36.67%(11) of females with history of previous abortion. We also found
      that 36.67%(11) of subjects with previous single abortion and 30%(9) of subjects
      with previous 2 or more abortions were suffering from depressive episode. None of
      the female suffered from psychotic disorder. CONCLUSIONS: The incidence of
      depression and anxiety is high in pregnancy after previous abortion and more in
      subjects who conceive earlier after previous abortion. These results warrant the
      need for screening all pregnancies for psychiatric morbidity after a previous
      abortion.

PMID- 22981049
TI  - Substance-induced psychotic disorders: 13-year data from a de-addiction centre
      and their clinical implications.
AB  - The relationship between substance use and psychotic disorder has been complex.
      Alcohol, cannabis, amphetamines, hallucinogens, and phencyclidine have been
      implicated as a causative factor for psychotic disorders. It is important to
      differentiate substance induced psychotic disorders (SIPDs) from primary
      psychotic disorders as management of the two conditions is different. There is
      paucity of research in the area of SIPD particularly from Asia. The present study
      was a retrospective study and it determines retrospectively the incidence rate
      and clinical characteristics of the SIPDs over a period of 13 years. The
      incidence of SIPDs was found to be 1.4% and all the subjects were males. In the
      present study, only alcohol and cannabis were implicated as causative agents for
      SIPDs. The most common type of psychosis was schizophrenia like psychosis, being
      more common in the cannabis group. The other forms of psychosis included
      delusional type, hallucinatory type and affective psychosis. 20% of the subjects
      had a change in diagnosis to either schizophrenia or affective psychosis on
      follow-up. The present study showed that the presentation of SIPDs is similar to
      the primary psychotic disorder and this has management implication.

PMID- 22981050
TI  - Applying mobile technologies to mental health service delivery in South Asia.
AB  - Mobile phones have increasingly assumed an important role in the treatment of
      mental disorders in high-income countries. This paper considers such
      possibilities in the South Asian context. First, a brief review of mobile phone
      use in mental disorders is provided. Next, data on the market penetration and
      dissemination of mobile phones in South Asia is presented. Finally, common
      barriers to treatment for mental disorders in South Asia are evaluated against
      solutions that could be derived from mobile technologies. Though not without
      their risks, mobile phones have the potential to increase engagement, treatment,
      and retention of South Asian patients with mental disorders in unprecedented
      ways.

PMID- 22981051
TI  - A comparison between acupuncture versus zolpidem in the treatment of primary
      insomnia.
AB  - BACKGROUND: To determine the relative efficacy of acupuncture and zolpidem in the
      treatment of primary insomnia, we administered a sleep quality scale to thirty
      three patients with primary insomnia randomly chosen to receive one of the two
      therapies at a psychosomatic clinic. METHODS: A study in the psychosomatic clinic
      at a teaching hospital in southern Taiwan from November 2007 to November 2008.
      The 19 patients in acupuncture group underwent one acupuncture session a week.
      The 14 patients in the control group took zolpidem 1# (10mg) every night. Members
      of both groups returned to our clinic once a week for four weeks. The main
      outcome measure was the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Both
      groups were found to have improved significantly. Using generalized estimating
      equation analysis to test the variance with group and time as factors, we found
      both groups improved over time at a similar rate (p=0.79). In regression
      analysis, setting the fourth total PSQI score to zero, the baseline PSQI score
      was 4.13 (p<0.001), the second score 1.32 (p=0.005), and the third 1.49 (p=0.03);
      men had a higher PSQI score 1.56 than women (p=0.02); the increasing age of one
      year would have lower PSQI score 0.08 (p<0.001) and increasing educational level
      of one year which would decrease PSQI score 0.25 (p=0.007). CONCLUSIONS:
      Acupuncture might be used as an alternative strategy compared to zolpidem for the
      treatment of primary insomnia.

PMID- 22981052
TI  - Public knowledge and beliefs about depression among urban and rural Chinese in
      Malaysia.
AB  - The study compared knowledge and beliefs about depression among urban and rural
      Chinese in a Malaysian sample. A total of 409 participants were asked to identify
      cases of depression varying in intensity from two vignettes and rate their
      beliefs regarding a list of possible causes and treatments for depression. The
      urban Chinese were more likely to identify depression as the problem in the
      vignette. Beliefs about causes of depression were factored into five components,
      whereas beliefs about treatment for depression factored into four components. The
      results indicated that the causes most strongly endorsed were stress and
      pressure, and standard treatments rated the highest as treatments for depression.
      Overall, depression literacy was moderate for Chinese Malaysians. The results are
      discussed in relation to Chinese cultural beliefs about depression. Limitations
      of this preliminary study were acknowledged.

PMID- 22981053
TI  - Mental health literacy survey among Sri Lankan carers of patients with
      schizophrenia and depression.
AB  - INTRODUCTION: Mental health literacy has been defined as knowledge and beliefs
      about mental disorders which aid their recognition, management or prevention.
      AIM: Preliminary investigation on mental health literacy among Sri Lankan carers
      of patients with Schizophrenia and Depression. METHOD: Cross sectional
      descriptive study investigated a convenience sample of 119 carers of a person
      with Depression or Schizophrenia attending a community clinic using vignettes
      adapted from an existing mental health literacy survey. RESULTS: The
      Schizophrenia vignette was reported as a crisis by 28% and 35.6% reported the
      Depression vignette as a crisis. Schizophrenia and Depression were identified as
      mental illnesses by 72% and 64% respectively. Persons with Schizophrenia and
      Depression were reported to be more violent than a member of the community by 61%
      and 60%. Psychiatrist's help was preferred as the therapeutic intervention in
      Schizophrenia (86.7%) and Depression (91.5%), whereas only 21.7% preferred
      traditional healers. Carers of persons with Schizophrenia (72%) and Depression
      (61%) held the attitude that the problem is a sign of personal weakness. Sixteen
      percent of carers wanted to avoid people with similar problems. DISCUSSION:
      Carers had stigmatising attitudes such as persons with mental illness were
      violent and the illness was a sign of personal weakness. A minority wanted to
      avoid persons with similar problems, indicating that maintaining social distance
      was not a major issue. Carers had good knowledge of help seeking locations with a
      majority identifying psychiatrists and psychiatric wards in general hospitals.
      CONCLUSION: The mental health literacy amongst the carers are lacking in certain
      areas. They have stigmatising attitudes towards people with mental illness.

PMID- 22981054
TI  - Explanatory models in patients with first episode depression: a study from north
      India.
AB  - The purpose of this work was to study the explanatory models of patients with
      first episode depression presenting to a tertiary care hospital located in North
      western India. One hundred sixty four consecutive patients with diagnosis of
      first episode depression (except severe depression with psychotic symptoms)
      according to the International Classification of Diseases-10th Revision (ICD-10)
      and >=18 years of age were evaluated for their explanatory models using the
      causal models section of Explanatory Model Interview Catalogue (EMIC). The most
      common explanations given were categorized into Karma-deed-heredity category
      (77.4%), followed by psychological explanations (62.2%), weakness (50%) and
      social causes (40.2%). Among the various specific causes the commonly reported
      explanations by at least one-fourth of the sample in decreasing order were: will
      of god (51.2%), fate/chance (40.9%), weakness of nerves (37.8%), general weakness
      (34.7%), bad deeds (26.2%), evil eye (24.4%) and family problems (21.9%). There
      was some influence of sociodemographic features on the explanations given by the
      patients. From the study, it can be concluded that patients with first episode
      depression have multiple explanatory models for their symptoms of depression
      which are slightly different than those reported in previous studies done from
      other parts of India. Understanding the multiple explanatory models for their
      symptoms of depression can have important treatment implications.

PMID- 22981056
TI  - Talking about stigma towards mental health professionals with psychiatry
      trainees: a movie club approach.
AB  - Psychiatry as a discipline is often perceived as 'different' by other medical
      professionals as much as by a common man. This perception of 'difference' may
      give rise to stigma both towards mental illness and to mental health
      professionals. Mental health professionals are thus both recipients of stigma and
      agents who can de-stigmatize psychiatry. A psychiatry movie club approach can be
      a very useful learning experience to understand various aspects of this
      stigmatization process. This paper presents a brief account of such an endeavour
      in which the film Gothika (2003) was used to help psychiatry trainees talk about
      their experiences with stigma towards mental illness as well as their profession.

PMID- 22981057
TI  - A synopsis of recent papers published in psychiatric journals in the Russian
      Federation.
AB  - Four influential papers that have appeared recently in the main psychiatric
      journals from Russia are summarized. The first paper examines socio-demographic
      profile and clinical manifestations and data of people with mental disorders
      attending the private psychiatric clinics. It was seen that about 50% of private
      mental health settings' patients had never consulted a public psychiatric service
      before seeking help at private psychiatric clinics. Private mental health
      services have proven their effectiveness in the treatment of non-psychotic
      disorders and intervention in early onset psychoses. The second paper describes
      neuropsychological and evolutionary approaches in understanding the comorbidity
      between depressive and anxiety disorders. It suggests that if anxiety disorder
      manifests as the first diagnosis, it is more likely that the person will have
      depression than vice versa. The next article concludes that there is a specific
      vulnerability of different groups of somatically ill patients to particular
      mental disorders: cancer is mainly associated with dissociative disorders and
      asthenia; patients with cardiac disorders are more likely to have comorbid
      anxiety disorders, hypochondriasis and severe depression. Patients with
      dermatological illnesses are more likely to have obsessive-compulsive disorder,
      delusional disorder and mild depression. The last paper discusses some social
      psychological and neuro-immunological parameters of people with "dangerous"
      professions. Using mathematical method, the authors created a model that can
      decrease the negative influence of work-related extreme factors.

PMID- 22981055
TI  - Outcomes that matter: a qualitative study with persons with schizophrenia and
      their primary caregivers in India.
AB  - BACKGROUND: Involving persons with schizophrenia and their families in designing,
      implementing and evaluating mental health services is increasingly emphasised.
      However, there is little information on desired outcomes from the perspectives of
      these stakeholders from low and middle income countries (LMIC). AIMS: To explore
      and define outcomes desired by persons with schizophrenia and their primary
      caregivers from their perspectives. METHOD: In-depth interviews were held with 32
      persons with schizophrenia and 38 primary caregivers presenting for care at one
      rural and one semi-urban site in India. Participants were asked what changes they
      desired in the lives of persons affected by the illness and benefits they
      expected from treatment. Data was analysed using thematic and content analysis.
      RESULTS: Eleven outcomes were desired by both groups: symptom control;
      employment/education; social functioning; activity; fulfilment of duties and
      responsibilities; independent functioning; cognitive ability; management without
      medication; reduced side-effects; self-care; and self-determination. Social
      functioning, employment/education and activity were the most important outcomes
      for both groups; symptom control and cognitive ability were more important to
      persons with schizophrenia while independent functioning and fulfilment of duties
      were more important to caregivers. CONCLUSIONS: Interventions for schizophrenia
      in India should target both clinical and functional outcomes, addressing the
      priorities of both affected persons and their caregivers. Their effectiveness
      needs to be evaluated independently from both perspectives.

PMID- 22981058
TI  - Transparency in psychiatric care.
AB  - Transparency in medical care is emerging as a new standard. In the United States,
      patients have always been able to access to their chart in accordance with the
      Health Insurance Portability and Accountability Act (HIPAA), established in 1996.
      Such access, nevertheless, can be time consuming and burdensome. Among the many
      provisions afforded by HIPAA are the security and privacy of health data.
      Physicians are recently coming to realize the benefits enjoyed by patients and
      the healthcare system when the information in a patient's chart is made available
      in real-time. Psychiatrists often find the concept of revealing their progress
      notes, however, quite provocative and controversial. In these evolving times, it
      is important for psychiatrists to recognize the potential consequences and
      advantages of sharing their progress notes with patients. This review provides
      guidelines for psychiatrists to follow regarding proper documentation of progress
      notes and how to successfully share that information with patients.

PMID- 22981059
TI  - Problematic internet behaviours among university students in Sri Lanka.

PMID- 22981060
TI  - Teachers' awareness about attention deficit hyperactivity disorder (ADHD) in
      Oman.

PMID- 22981061
TI  - Problematic internet use and mental health problems.

PMID- 22981062
TI  - Postoperative manic syndrome following removal of a giant cerebral hydatid cyst.

PMID- 22981063
TI  - Globalisation and mental health: the Lyon Declaration.

PMID- 22981064
TI  - Mental health in the low income Pacific Island countries--time for change in
      paradigms.

PMID- 22981066
TI  - Reality or dream of fluorescence-guided pancreatic cancer surgery?

PMID- 22981069
TI  - [Lymphogranuloma venereum: diagnostic utility of the polymerase chain reaction
      for Chlamydia trachomatis].

PMID- 22981070
TI  - [Leptospirosis in a sewer worker in Madrid: the role of molecular diagnosis].

PMID- 22981071
TI  - [Fat embolism syndrome after bone fractures].
AB  - OBJECTIVES: To review the incidence, clinical features, diagnosis, therapy and
      mortality rates of fat embolism syndrome (FES) in a tertiary referral hospital in
      the last decade. PATIENTS AND METHODS: Retrospective and descriptive study of
      patients diagnosed with post-traumatic FES between january 2001 and december
      2011. RESULTS: A total of 19 patients, 16 men and 3 women, with an average age of
      27 years were evaluated. All had long bone fractures, multiple in 78.9%, as a
      result of multiple injuries. Respiratory symptoms were the most frequent (89.5%),
      followed by neurological symptoms (68.4%) and petechial rash (63.2%). The average
      time of presentation of the syndrome after admission was 42 hours. All patients
      underwent early stabilisation of the fracture prior to the embolic event.
      Steroids prophylaxis was not used in any of the cases. Definitive surgical
      treatment had mean delay of 7 days. The mean hospital stay was 34 days. The
      overall incidence of FES was 0.14%, and mortality was 10.5%. CONCLUSIONS: Post
      traumatic FES mainly affected young patients with multiple injuries and long bone
      fractures. They all had symptoms of the classic clinical triad (respiratory,
      neurological, rash) after an initial asymptomatic period of less than 2 days. The
      overall incidence was low.

PMID- 22981072
TI  - [Bone infarcts with sickle cell trait].

PMID- 22981073
TI  - Influence of dispersion and aging on the frequency of some common interventions
      in the elderly.
AB  - BACKGROUND AND OBJECTIVE: Public administrations have to procure equitable care
      that compensates resistance factors such as communication problems and those
      arising from aging. Our objective was to analyze the influence of population
      dispersion and aging on the frequency rate of some common surgical procedures in
      elderly patients. PATIENTS AND METHODS: We used the database of surgical activity
      of the only hospital in a Spanish province to identify cataract surgeries, hip
      replacements and pacemaker implants performed during 2010. Using the National
      Statistics Institute Census, we calculated the rate for each procedure and the
      proportion of inhabitants over 65 in each municipality. Time needed to access the
      hospital by road from each municipality was used as a measure of dispersion.
      RESULTS: The population was distributed into 339 population centers, 90% of which
      had less than 1,000 inhabitants. The worst communicated populations were smaller
      (r=-0.194; P<.0001) and had a higher proportion of elderly (r=0.406; P<.0001). No
      relationship was found between the frequentation of the selected interventions
      and the number of inhabitants or travel time. Similarly, no differences were
      found when the analysis was done by pooling the population for 30 minutes
      isochrones. The percentage of those over 65 years was independently associated to
      the frequency rate of cataract surgery (beta=0.211; P<.001) and showed a trend to
      increased frequency for the implantation of pacemakers and hip replacements.
      CONCLUSIONS: Our study shows that, with the current organization of care and in
      the territory analyzed, neither population dispersion nor aging seems to reduce
      frequentation of several interventions typical of the elderly population.

PMID- 22981074
TI  - [New human immunodeficiency virus diagnoses: a never-ending problem].

PMID- 22981075
TI  - Comparison of endothelialization and neointimal formation with stents coated with
      antibodies against CD34 and vascular endothelial-cadherin.
AB  - Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late
      endothelial progenitor cells (EPC). Therefore, VE-cadherin could be an ideal
      target surface molecule to capture circulating late EPC. In the present study, we
      evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might
      accelerate endothelial recovery and reduce neointimal formation more than anti
      CD34 antibody-coated stents (CD34 stents) through the superior ability to capture
      the late EPC. The stainless steel stents were coated with anti-human VE-cadherin
      antibodies or anti-human CD34 antibodies under the same condition. In vitro, VE
      cad stents showed higher number of adhering EPC (823.6 +/- 182.2 versus 379.2 +/-
      137.2 cells per HPF, p < 0.001). VE-cad stents also demonstrated better specific
      capturing of cells with endothelial lineage markers than CD34 stents did in flow
      cytometric analysis. VE-cad stents showed more effective re-endothelialization
      after 1 h, 24 h, and 3 days in vivo. At 42 days, VE-cad stents demonstrated
      significantly smaller neointima area (0.92 +/- 0.38 versus 1.24 +/- 0.41 mm(2), p
      = 0.002) and significantly lower PCNA positive cells in neointima (1684.8 +/-
      658.8/mm(2) versus 2681.7 +/- 375.1/mm(2), p = 0.008), compared with CD34 stents.
      In conclusion, VE-cad stents captured EPC and endothelial cells more selectively
      in vitro, accelerated re-endothelialization over stents, and reduced neointimal
      formation in vivo, compared with CD34 stents.

PMID- 22981076
TI  - Influence of surface charge and inner composition of nanoparticles on
      intracellular delivery of proteins in airway epithelial cells.
AB  - The delivery of protein in the airway using nanoparticles (NP) is an emerging
      strategy that shows encouraging results in vivo for several applications.
      However, the mechanisms by which NP deliver proteins to the inside of cells
      remain poorly understood. In this study, we investigated the intracellular
      delivery of ovalbumin (OVA) in human airway cells by two porous cationic
      polysaccharides nanoparticles. These NP have the same surface charge density but
      differ in that their inner core contains either cationic or anionic charges
      (respectively: NP(+) and DGNP(+)). Confocal microscopy showed a rapid uptake of
      both NP by human airway cells, followed by a significant accumulation in clathrin
      vesicles and early endosomes. Both NP were found to associate OVA in a
      quantitative manner, and this association was stable even in presence of serum
      proteins. We observed that the two NP greatly increased OVA uptake by human
      airway cells, meanwhile FRET studies using FITC-labelled NP and TRITC-labelled
      OVA showed a gradual release of OVA from NP within cells, and this was much
      faster with DGNP(+) than NP(+). These results were confirmed using OVA-DQ to
      follow OVA degradation fragments within cells. Both NP increased intracellular
      proteolysis of OVA, however DGNP(+) facilitated OVA escape from endosomes.
      Studies with trypsin and pepsin at different pH strongly suggested that both NP
      can protect (in the extracellular medium) or promote (in acidic endosomes)
      protein proteolysis, depending on the environment. Interestingly, the mechanisms
      involved could be explained as a function of protein global charge at different
      pH. All these results confirm the importance of not only the surface charge but
      also the inner composition of NP in determining their efficacy as tools for the
      delivery of proteins to different cellular compartments.

PMID- 22981077
TI  - Endocytosis, intracellular transport, and exocytosis of lanthanide-doped
      upconverting nanoparticles in single living cells.
AB  - Lanthanide-doped upconverting nanoparticles (UCNPs) have recently attracted
      enormous attention in the field of biological imaging owing to their unique
      optical properties (near-infrared excitation followed by photoluminescence in the
      visible spectral range). For biological applications, it is critical to
      understand the interaction between these nanoparticles and biological systems at
      the cellular level. In this paper, using epi-fluorescence microscopy with 980-nm
      excitation, a full intracellular pathway composed of endocytosis, active
      transport, and exocytosis was clearly visualized for PEG-phospholipid-coated
      UCNPs in single HeLa cells, which was experimentally feasible mostly thanks to
      the excellent photostability and low cytotoxicity thereof. Each step in the
      pathway was characterized and identified by various chemical inhibition studies
      and spectroscopic measurements.

PMID- 22981078
TI  - Orbital trauma.
AB  - Orbital injuries are common and a common cause of blindness. The first priority
      for these injuries is the health of the globe. Imaging is imperative for
      diagnosing orbital fractures, as clinical examination cannot thoroughly assess
      their presence or severity. When treatment is indicated, an anatomic
      reconstruction of the internal orbit is critical to the proper position and
      function of the ocular globe.

PMID- 22981079
TI  - Preface.

PMID- 22981080
TI  - CT & CBCT imaging: assessment of the orbits.
AB  - The orbits can be visualized easily on routine or customized protocols for
      computed tomography (CT) or cone beam CT (CBCT) scans. Detailed orbital
      investigations are best performed with 3-dimensional imaging methods. CT scans
      are preferred for visualizing the osseous orbital anatomy and fissures while
      magnetic resonance imaging is preferred for evaluating tumors and inflammation.
      CBCT provides high-resolution anatomic data of the sinonasal spaces, airway, soft
      tissue surfaces, and bones but does not provide much detail within the soft
      tissues. This article discusses CBCT imaging of the orbits, osseous anatomy of
      the orbits, and CBCT investigation of selected orbital pathosis.

PMID- 22981081
TI  - [Prognosis of cardiorenal syndrome in patients with acute coronary syndrome].
AB  - BACKGROUND AND OBJECTIVE: The cardiorenal syndrome (CRS) includes numerous
      pathologies affecting the heart and kidney. The objective of this study is to
      know the characteristics and prognosis of the CRS in patients with acute coronary
      syndrome (ACS). PATIENTS AND METHOD: A prospective study of 87 patients with ACS
      with and without ST-segment elevation at high risk and heart failure. We analysed
      the presence of CRS and its relationship with epidemiological variables,
      clinical, analytical and complementary explorations. Through a Cox regression
      model we investigated its relationship with mortality in the subsequent 6 months
      of the event. RESULTS: Patients with CRS (43.7%) were more frequently women,
      older, with more prior cardiovascular disease and a profile of higher risk. The
      prognosis was significantly worse in this group and the CRS was an independent
      predictor of mortality (hazard ratio 3.08; 95% confidence interval 1.13-8,40;
      P=.029). CONCLUSIONS: The presence of CRS has an influence in the prognosis of
      patients who suffer an ACS high-risk and increases the likelihood of dying during
      6 months after the event.

PMID- 22981082
TI  - [Reply].

PMID- 22981083
TI  - [Chemical submission, opportunistic or premeditated].

PMID- 22981084
TI  - [Dysphagia and loss of weight in a 76-year-old female patient].

PMID- 22981086
TI  - [Transient biventricular dysfunction after pericardiocentesis].

PMID- 22981085
TI  - [Detection of thyroid dysfunction in pregnant women: universal screening is
      justified].
AB  - There is a controversy among different scientific societies in relation to the
      recommendations on whether universal screening for the detection of thyroid
      dysfunction during gestation should be performed or not. Although various studies
      have shown an association between subclinical hypothyroidism or hypothyroxinemia
      with obstetric problems and/or neurocognitive impairment in the offspring, no
      evidence on the possible positive effects of treatment of such conditions with
      thyroxin has been demonstrated so far. However, there is a general agreement
      about the need for treatment of clinical hypothyroidism during pregnancy and the
      risks of not doing so. Because it is a common, easily diagnosed and effectively
      treated disorder without special risk, the working Group of Iodine Deficiency
      Disorders and Thyroid Dysfunction of the Spanish Society of Endocrinology and
      Nutrition and Spanish Society of Gynaecology and Obstetrics recommends an early
      evaluation (before week 10) of thyroid function in all pregnant women. Given the
      complex physiology of thyroid function during pregnancy, hormone assessment
      should be performed according to reference values for each gestational trimester
      and generated locally in each reference laboratory. Thyrotropin determination
      would be sufficient for screening purposes and only if it is altered, free
      thyroxin or total thyroxin would be required. Adequate iodine nutrition is also
      highly recommended before and during pregnancy to contribute to a normal thyroid
      function in the pregnant women and fetus.

PMID- 22981087
TI  - Fatal coronary artery intimal hyperplasia due to amphetamine use.
AB  - BACKGROUND: Amphetamines have been reported to cause myocardial infarct, cerebral
      hemorrhage, aortic dissection, hypertension, vasculitis, aneurysms, and,
      occasionally, death from direct toxicity. To date, there have been no reports of
      coronary intimal hyperplasia in an amphetamine user. METHODS: A 29-year-old male
      was found collapsed after jogging. He had been taking amphetamines for 11 years
      for attention deficit/hyperactivity disorder. Past medical history was positive
      for mild hypertension and migraine headaches. He underwent a complete autopsy and
      drug screen. RESULTS: At gross autopsy his left anterior descending (LAD)
      coronary artery was occluded and he had an old myocardial infarct in the anterior
      wall of the left ventricle. Microscopic findings included occlusive intimal
      hyperplasia (positive for smooth muscle actin) in the LAD and an old left
      ventricular anterior wall infarct surrounded by acute infarct. CONCLUSION: In
      addition to other reported adverse effects, amphetamines can also cause occlusive
      intimal hyperplasia of the coronary arteries.

PMID- 22981088
TI  - Latent adrenal Ewing sarcoma family of tumors: A case report.
AB  - Ewing sarcoma family of tumors (ESFT) is derived from the neural crest, which
      originates from basal embryo cells in the primitive neural tube. ESFT often
      arises at the bone, chest wall, and soft tissues of the thoracic region. However,
      ESFT that arises from the adrenal gland is much rarer and it is usually revealed
      by clinical symptoms. We report an autopsy case of suicidal hanging, in which
      adrenal ESFT was incidentally revealed. To our knowledge, this is the first case
      of latent ESFT arising from the adrenal gland. Autopsy can sometimes reveal
      latent disease. Some of these latent diseases are very rare and we would not be
      able to detect them without a complete autopsy. As forensic pathologists, we
      should attempt to perform a complete autopsy and report new discoveries for the
      development of medicine.

PMID- 22981089
TI  - An autopsy case of bilateral adrenal pheochromocytoma-associated cerebral
      hemorrhage.
AB  - The autopsy findings of a 30-year-old woman who died of cerebral hemorrhage
      induced by bilateral adrenal pheochromocytoma are presented. The cerebral
      hemorrhage was shown on the left cerebral hemisphere widely. Her both adrenal
      glands were severe swelling, and their parenchyma was occupied by a dark red
      brown tumorous positive for chromogranin A. The serum catecholamine and their
      metabolite, vanillylmandelic acid (VMA) levels were markedly high. Furthermore,
      cardiac hypertrophy and sclerosis of the arteries of various organs had
      progressed, suggesting an influence of persistent endocrinal hypertension. The
      measurement of serum VMA level was thought to be valuable for a postmortem
      diagnosis of pheochromocytoma. Bilateral adrenal pheochromocytoma may have
      excessively secreted catecholamine and subsequently caused secondary
      hypertension, leading to cerebral hemorrhage.

PMID- 22981090
TI  - Conditioned pain modulation in populations with chronic pain: a systematic review
      and meta-analysis.
AB  - A systematic literature review and meta-analysis were undertaken to determine if
      conditioned pain modulation is dysfunctional in populations with chronic pain.
      Studies that used a standardized protocol to evaluate conditioned pain modulation
      in a chronic pain population and in a healthy control population were selected
      and reviewed. Thirty studies were included in the final review, encompassing data
      from 778 patients and 664 control participants. Across all studies there was a
      large effect size of .78, reflecting reduced conditioned pain modulation in the
      patient group. Analysis of moderator variables indicated a significant influence
      of participant gender and age on the effect size. Methodological moderator
      variables of type of outcome measure, type of test stimulus, type of conditioning
      stimulus, and the level of conditioning stimulus pain were not significant. A
      risk of bias assessment indicated that poor blinding of assessors and a lack of
      control of confounding variables were common. It is concluded that conditioned
      pain modulation is impaired in populations with chronic pain. Future studies
      should ensure adequate matching of participant age and gender between patient and
      control groups, blinding of the assessors obtaining the outcome measures, and
      more rigorous control for variables known to influence the level of modulation.
      PERSPECTIVE: This review compared the efficacy of conditioned pain modulation
      between chronic pain and healthy populations. The finding of impaired modulation
      in the chronic pain groups highlights the dysfunction of endogenous pain
      modulatory mechanisms in this population.

PMID- 22981091
TI  - Association between polymorphisms of DNA repair gene ERCC5 and oral squamous cell
      carcinoma.
AB  - OBJECTIVE: Short nucleotide polymorphism in ERCC5 (rs751402), a key molecule in
      DNA damage repair, was analyzed in 575 individuals who were either control
      subjects with no clinical evidence of malignant transformation of the oral mucosa
      or subjects with oral squamous cell carcinoma (OSCC). STUDY DESIGN: All
      participants provided a blood sample, demographic data, and information on
      habitual use of tobacco, alcohol, and areca nut. RESULTS: rs751402 homozygocity
      for C allele was found to confer a statistically significant protection against
      OSCC (adjusted odds ratio 0.56, 95% confidence interval 0.35-0.89; P = .01),
      whereas rs751402 T alleles were associated with increased risk. CONCLUSIONS: Our
      findings suggest that there is an association between rs751402 polymorphism and
      incidence of oral cancer. ERCC rs751402 CC genotype is significantly associated
      with decreased risk of OSCC, whereas the T allotype is correlated with higher
      risk of OSCC.

PMID- 22981092
TI  - Depth of penetration of methylene blue in mandibular cortical bone.
AB  - BACKGROUND: Surgeons treating keratinizing odontogenic tumors (KOT) and other
      intrabony lesions frequently use methylene blue as an adjunct in peripheral
      ostectomy in estimating the depth of bone that has been removed. Depth of
      methylene blue penetration in cortical bone has not been evaluated. STUDY DESIGN:
      Specimens of mandible harvested from 9 fresh unembalmed cadaveric mandibles were
      stained with methylene blue. A microcaliper was used to measure total thickness
      of the cortical specimen along with the amount of dye penetration within the
      cortical block to the nearest 0.1 mm. RESULTS: Average depth of dye penetration
      was 0.48 mm in the symphysis. Average dye penetration was 0.53 mm in the body.
      Average depth of penetration of 0.42 mm in the angle. CONCLUSIONS: The use of
      methylene blue as a depth gauge to ensure adequate ostectomy with a single
      application of the dye may be inadequate to ensure complete removal of lesion
      from bony wall.

PMID- 22981093
TI  - Intraoral application of hyperdry amniotic membrane to surgically exposed bone
      surface.
AB  - Hyperdry amniotic membrane, a novel preservable material derived from the human
      amnion, has been introduced clinically in ophthalmology and other fields. This
      membrane is available as a wound dressing material for surgical wounds of the
      tongue and buccal mucosa but has not been used on wounds of the alveolar mucosa.
      This paper reports 2 cases in which intraoral alveolar wounds with bone exposure
      were successfully treated with the use of hyperdry amniotic membrane: a 74-year
      old woman with gingival leukoplakia of the edentulous mandible, and a 43-year-old
      man who underwent vestibuloplasty of the reconstructed mandible. The results
      indicate that the hyperdry amniotic membrane is a useful dressing material, not
      only for soft tissue wounds, but also for exposed bone in the oral cavity. 

PMID- 22981095
TI  - Solid-type primary intraosseous squamous cell carcinoma of the mandible: a case
      report with histopathological and imaging features.
AB  - Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant
      odontogenic tumor arising from odontogenic epithelial remnants within the
      jawbones. PIOSCC is histopathologically divided into 3 types: solid-type
      carcinoma, carcinoma derived from a keratocystic odontogenic tumor, and carcinoma
      derived from an odontogenic cyst. In this article, we report a case of solid-type
      PIOSCC involving reactive bone formation in the mandible in a 60-year-old female
      patient together with its histopathological and imaging findings.

PMID- 22981094
TI  - Analgesic and adjuvant anesthetic effect of submucosal tramadol after mandibular
      third molar surgery.
AB  - OBJECTIVE: The aim of this study was to assess analgesic and adjuvant anesthetic
      effects of submucosal tramadol after third molar extraction. STUDY DESIGN: In
      this double-blind, split-mouth, placebo-controlled, single-dose, crossover
      investigation, 52 patients underwent mandibular third molar extraction under
      local anesthesia. Surgical side was randomly assigned to submucosal 2 mL 100 mg
      tramadol injection (group T) or normal saline solution (group P) immediately
      after surgery. Anesthetic blockade duration, time of intake and amount of
      analgesic rescue drug, and postoperative pain intensity were recorded immediately
      after anesthesia cessation and 4, 8, 24, 48, and 72 hours after surgery. Data
      were submitted to analysis of variance and Wilcoxon tests. RESULTS: Anesthetic
      blockade duration between groups was similar. Group T took significantly less
      rescue drug after 72 hours (P = .008). Time elapsed before first intake of rescue
      drug was longer (P = .006), and pain intensity was significantly lower (P = .001)
      in group T. CONCLUSIONS: Submucosal tramadol injection after oral surgery
      improved postoperative analgesia, but did not extend anesthetic action duration.

PMID- 22981096
TI  - Distal cervical caries in second molars associated with impacted mandibular third
      molars: a case-control study.
AB  - OBJECTIVE: This study compares the incidence of cervical caries in the mandibular
      second molar associated with impacted third molar with that of fully erupted
      third molar. STUDY DESIGN: The participants consisted of subjects with second
      molar adjacent to an impacted third molar (study group), and subject with second
      molar adjacent to a fully erupted third molar (control group). Incidence of
      cervical caries on the second molar and other variables were recorded and
      analyzed for both groups. RESULTS: The incidence of distal cervical caries in the
      study group was 15.7% and no case of distal cervical caries was seen in the
      control (P = .000). DMF score in study group was significantly lower than in
      control (P = .000). The incidence of distal cervical caries increased with age of
      subjects and DMF scores (P <= .05). CONCLUSIONS: Distal cervical caries in second
      molars is a phenomenon limited only to impacted mandibular third molars.

PMID- 22981097
TI  - Diagnostic accuracy of Digora Optime storage phosphor plates for proximal
      subsurface demineralization: effect of different exposure times.
AB  - OBJECTIVE: The aim of this study was to compare the diagnostic accuracy of F
      speed film and storage phosphor plate (SPP) exposed with different exposure times
      for the detection of artificial enamel subsurface demineralization. STUDY DESIGN:
      Standard enamel windows of extracted premolars were exposed to a demineralizing
      solution. All teeth were radiographed before and after acid application with F
      speed films and SPPs. Films were exposed for 0.25 seconds and SPPs were exposed
      using 4 exposure times. Receiver operating characteristic analysis was used for
      diagnostic accuracy (A(z)). RESULTS: Significant differences were obtained among
      A(z)s of 0.08- versus 0.12-seconds and 0.10- versus 0.12-second exposed SPPs (P <
      .05). A(z)s of films were higher than the SPPs exposed with 0.08, 0.10, and 0.12
      seconds (P < .05). No difference was found between the A(z)s of the 2 systems
      when SPPs were exposed for 0.16 seconds (P > .05). CONCLUSIONS: Diagnostic
      accuracy of films and SPPs was not impaired when exposure time was 36% reduced
      for the latter; however, diagnosis was impaired when reduced 52%.

PMID- 22981098
TI  - Scarring and chronic ulceration of the floor of the mouth.

PMID- 22981099
TI  - Comparison of cone-beam computed tomography with intraoral photostimulable
      phosphor imaging plate for diagnosis of endodontic complications: a simulation
      study.
AB  - OBJECTIVES: The objective of this study was to compare the sensitivity and
      reliability of cone-beam computed tomography (CBCT) and intraoral photostimulable
      phosphor (PSP) imaging plate for diagnosis of endodontic complications. STUDY
      DESIGN: Seventy-two human mandibular teeth were used, including 24
      incisors/canines, 24 premolars, and 24 molars. Three images were taken from each
      group of teeth with intraoral PSP, CBCT-NewTom, and CBCT-ProMax. RESULTS: The
      sensitivity of PSP, CBCT-NewTom, and CBCT-ProMax was 76.39%, 80.56%, and 94.44%
      for detecting cast post deviation; 98.61%, 100%, and 100% for external root
      resorption; 86.11%, 31.94%, and 36.11% for fractured file; and 66.67%, 90.28%,
      and 86.11% for lateral root perforation respectively. The intertechnique
      reliability (kappa statistics) was 58.4% for the 2 CBCT techniques, 20.1% and
      18.8% for CBCT-NewTom and CBCT-ProMax versus PSP respectively. CONCLUSIONS: Given
      strengths and weaknesses of the techniques as well as the cost, CBCT is
      recommended as a complementary but not routinely used diagnostic method for
      endodontic complications not usually detected by conventional methods.

PMID- 22981100
TI  - Diabetic foot complications in Malta: prevalence of risk factors.
AB  - AIMS: The main objective of this research was to identify the prevalence of
      diabetes-related lower-extremity complications in a cohort of Maltese patients
      living with type 2 diabetes. METHODS: A retrospective study was conducted on a
      cohort of 243 patients living with type 2 diabetes mellitus in two Maltese Health
      Centre catchment areas. A convenience sampling was adopted to recruit subjects
      from a local pilot diabetes foot screening program. The clinical assessments used
      during this screening program were based on validated and previously published
      tools such as: neuropathy disability score, vibration perception threshold,
      Semmes-Weinstein monofilaments, vascular status and foot deformities were
      evaluated. RESULTS: The results from this study demonstrate that risk factors for
      foot deterioration and ulceration are common in Maltese population living with
      type 2 diabetes. Whilst, metabolic outcomes such as hypertension and
      dyslipidaemia were present in most subjects, peripheral vascular disease,
      peripheral sensory neuropathy and foot deformities were also common. Twenty-six
      per cent of the sample had to be referred for further vascular assessment
      following this screening program due to their critical vascular status.
      CONCLUSIONS/INTERPRETATION: A significant proportion of Maltese participants
      living with type 2 diabetes presented with vascular insufficiency, abnormal
      neural function and deformities in the feet. Metabolic outcomes such as high
      blood pressure and high levels of cholesterol were also highly prevalent.
      Strengthening of existing screening structures is imperative in order to reduce
      the burden of this disease in Malta.

PMID- 22981101
TI  - Americans' choice for health.

PMID- 22981102
TI  - Cracking ENCODE.

PMID- 22981103
TI  - Europe--the great divide.

PMID- 22981105
TI  - Kerin O'Dea: improving the health of Indigenous Australians.

PMID- 22981106
TI  - Academic output of 9 years of EU investment into health research.

PMID- 22981107
TI  - Doubts about the evidence that foreign aid for health is displaced into non
      health uses.

PMID- 22981108
TI  - Benefits of lifestyle interventions: precise input estimates needed.

PMID- 22981110
TI  - Protocols for uncontrolled donation after circulatory death.

PMID- 22981113
TI  - The last straw.

PMID- 22981114
TI  - Location of induction of labour must be considered further.

PMID- 22981115
TI  - A Littre bleed.

PMID- 22981116
TI  - Routine testing for HIV in patients undergoing elective surgery.

PMID- 22981117
TI  - Health at the Rio+20 negotiations.

PMID- 22981118
TI  - Clinical features of de novo CD25(+) diffuse large B-cell lymphoma.
AB  - CD25 (interluekin-2 receptor) expression in diffuse large B-cell lymphoma (DLBCL)
      cells has been not examined. To characterize CD25(+) DLBCL, 123 patients, who
      were newly diagnosed with DLBCL, were analyzed by single-color flow cytometry
      (FCM). CD25-positivity was significantly  higher in DLBCL patients (n = 123; mean
      +/- SD, 27.8 +/- 30.6%) than in those with reactive lymphadenopathy (n = 16; mean
      +/- SD, 8.6 +/- 4.3%) and follicular lymphoma (n = 60; mean +/- SD,  12.7 +/-
      12.4%). By two-color FCM, CD25/CD19 or CD25/CD20 dual positivity in DLBCL
      patients was shown: mean +/- SD, 63.7 +/- 25.5% (n = 13) and 55.0 +/- 28.1% (n =
      14), respectively. Eighty-two percent  of the patients with DLBCL received
      rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine and
      prednisone) chemotherapy. A cut-off value of 60% with CD25-positivity clearly
      divided patients with DLBCL into two groups: CD25-high or CD25-low DLBCL.
      Although clinical and immunophenotypic  features were not significantly different
      in both groups, the former showed a significantly poorer response and more
      inferior progression-free survival than the latter. CD25 may be a new prognostic
      marker and could be a therapeutic target in DLBCL.

PMID- 22981119
TI  - A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive
      hearing impairment.
AB  - CaBPs are a family of Ca(2+)-binding proteins related to calmodulin and are
      localized in the brain and sensory organs, including the retina and cochlea.
      Although their physiological roles are not yet fully elucidated, CaBPs modulate
      Ca(2+) signaling through effectors such as voltage-gated Ca(v) Ca(2+) channels.
      In this study, we identified a splice-site mutation (c.637+1G>T) in Ca(2+)
      binding protein 2 (CABP2) in three consanguineous Iranian families affected by
      moderate-to-severe hearing loss. This mutation, most likely a founder mutation,
      probably leads to skipping of exon 6 and premature truncation of the protein
      (p.Phe164Serfs(*)4). Compared with wild-type CaBP2, the truncated CaBP2 showed
      altered Ca(2+) binding in isothermal titration calorimetry and less potent
      regulation of Ca(v)1.3 Ca(2+) channels. We show that genetic defects in CABP2
      cause moderate-to-severe sensorineural hearing impairment. The mutation might
      cause a hypofunctional CaBP2 defective in Ca(2+) sensing and effector regulation
      in the inner ear.

PMID- 22981121
TI  - Immunological status in patients undergoing in vitro fertilisation: responses to
      hormone treatment and relationship to outcome.
AB  - We aimed to prospectively investigate the paternal antigen-induced cytokine
      secretion by peripheral blood mononuclear cells (PBMCs) in response to hormone
      treatment in women undergoing in vitro fertilisation (IVF) and to examine the
      predictive value of the cytokine secretion profile in the outcome of IVF
      treatment, in a pilot study. Twenty-five women were included and IVF treatment
      was successful for six and unsuccessful for 19 women. Blood samples were
      collected before IVF treatment, on four occasions during IVF and four weeks after
      embryo transfer. The numbers of Th1-, Th2- and Th17-associated cytokine-secreting
      cells and cytokine levels in cell supernatants were analysed by enzyme-linked
      immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex
      assay. None of the cytokines (IFN-gamma, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17,
      TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of
      the cytokines reached their peak levels at ovum pick-up, suggesting an enhancing
      influence of the hormonal stimulation. Pregnancy was associated with a high
      number of IL-4-, IL-5- and IL-13-secreting cells four weeks after ET. In
      conclusion, the results do not support our hypothesis of a more pronounced
      peripheral Th1 and Th17 deviation towards paternal antigens in infertile women
      with an unsuccessful IVF outcome, although this is based on a small number of
      observations. A larger study is required to confirm this conclusion. Higher
      numbers of Th2-associated cytokine-secreting cells in pregnant women four weeks
      after ET do corroborate the hypothesis of a Th2 deviation during pregnancy.

PMID- 22981120
TI  - A population-based study of autosomal-recessive disease-causing mutations in a
      founder population.
AB  - The decreasing cost of whole-genome and whole-exome sequencing has resulted in a
      renaissance for identifying Mendelian disease mutations, and for the first time
      it is possible to survey the distribution and characteristics of these mutations
      in large population samples. We conducted carrier screening for all autosomal
      recessive (AR) mutations known to be present in members of a founder population
      and revealed surprisingly high carrier frequencies for many of these mutations.
      By utilizing the rich demographic, genetic, and phenotypic data available on
      these subjects and simulations in the exact pedigree that these individuals
      belong to, we show that the majority of mutations were most likely introduced
      into the population by a single founder and then drifted to the high carrier
      frequencies observed. We further show that although there is an increased
      incidence of AR diseases overall, the mean carrier burden is likely to be lower
      in the Hutterites than in the general population. Finally, on the basis of
      simulations, we predict the presence of 30 or more undiscovered recessive
      mutations among these subjects, and this would at least double the number of AR
      diseases that have been reported in this isolated population.

PMID- 22981122
TI  - Preliminary investigation on the relationship of Raman spectra of sheep meat with
      shear force and cooking loss.
AB  - A prototype handheld Raman system was used as a rapid non-invasive optical device
      to measure raw sheep meat to estimate cooked meat tenderness and cooking loss.
      Raman measurements were conducted on m. longissimus thoracis et lumborum samples
      from two sheep flocks from two different origins which had been aged for five
      days at 3-4 degrees C before deep freezing and further analysis. The Raman data
      of 140 samples were correlated with shear force and cooking loss data using PLS
      regression. Both sample origins could be discriminated and separate correlation
      models yielded better correlations than the joint correlation model. For shear
      force, R(2)=0.79 and R(2)=0.86 were obtained for the two sites. Results for
      cooking loss were comparable: separate models yielded R(2)=0.79 and R(2)=0.83 for
      the two sites. The results show the potential usefulness of Raman spectra which
      can be recorded during meat processing for the prediction of quality traits such
      as tenderness and cooking loss.

PMID- 22981123
TI  - Meningovascular tuberculosis: case study of an atypical presentation.

PMID- 22981124
TI  - [Precision in historical quotations].

PMID- 22981125
TI  - [Competence in dementia: the unfinished task before us].

PMID- 22981126
TI  - [Complications of association magnesium sulfate with nicardipine during
      preeclampsia: report of 2 cases].
AB  - The authors report a heart failure and a collapse following concurrently
      administration of nicardipine and magnesium sulfate. These two drugs have
      potential negative inotropic effect and decrease systemic vascular resistance.
      Magnesium sulfate is the first-line treatment for the prevention of primary and
      recurrent eclamptic seizures. Combination with calcium channel blockers should be
      used cautiously.

PMID- 22981127
TI  - [The importance of functional assessment in Spanish men and women over 65 years
      old].

PMID- 22981128
TI  - [Telemedicine, also a tool for the family doctor].

PMID- 22981129
TI  - [Prevalence of caregiver burden, associated factors, and their relationship with
      family function, in caregivers of patients within the Interdisciplinary
      Rehabilitation Process in the University Clinic of Sabana (Colombia)].

PMID- 22981130
TI  - [Subliminal tobacco advertising in Spanish television series].

PMID- 22981131
TI  - [Patients with adverse drug reactions have a higher prevalence of emotional
      disorders].
AB  - AIM: To examine the frequency of emotional disorders (anxiety and depression) in
      patients with adverse drug reactions (ADR), compared with that in patients
      without those disorders. STUDY DESIGN: Case-control. SETTING: Santa Maria de
      Benquerencia Health Centre (Toledo). PARTICIPANTS: Patients over 14 years old of
      both sexes managed in a Primary Care Clinic. MEASUREMENTS AND RESULTS: A total of
      311 patients (108 cases and 203 controls) were included, of whom 53.7% were male.
      The mean age was 54.1 years in cases, and 46.0 in controls (t=4.254; P<.001).
      Antecedents of anxiety were presented in 45.5% of cases, and those of depression
      in 41.7%, versus 19.7% and 15.3%, respectively, in controls (P<.001). Mean
      chronic illnesses were 5.8 in cases and 3.5 in controls (P<.001). Mean number of
      drugs consumed was 3.7 in cases and 1.7 in controls (P<.001). In the logistic
      regression, the probability of having had anxiety was 2.5 times higher in
      patients with ADR (95%CI 1.12-4.51), and the probability of having had depression
      was twice as likely(1.06-3.66). Drug groups with a higher number of ADR were
      those of the central nervous system, antibiotics and antiinflammatories.
      CONCLUSIONS: 1) ADR is associated with anxiety and depression, and it can be used
      as a marker of social issues. 2) Attention must be paid to patients with anxiety
      or depression when making out prescriptions. 3) Antibiotics, antiinflammatories
      and drugs acting on the central nervous system are more likely to produce ADR.

PMID- 22981132
TI  - [Primary care and rehabilitation: what do health centres think about the
      relationships between healthcare levels?].

PMID- 22981134
TI  - [Drugs withdrawn from public funding].

PMID- 22981135
TI  - [Primary care doctors in HIV prevention].

PMID- 22981136
TI  - Neoadjuvant hormonal therapy use and the risk of death in men with prostate
      cancer treated with brachytherapy who have no or at least a single risk factor
      for coronary artery disease.
AB  - BACKGROUND: Neoadjuvant hormone therapy (NHT) use is associated with an increased
      risk of all-cause mortality (ACM) in men with a history of coronary artery
      disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction
      (MI). However, its effect in men with no or at least a single risk factor for CAD
      stratified by prostate cancer (PCa) aggressiveness is unknown. OBJECTIVE: To
      assess whether NHT use affects the risk of ACM in men with low-, intermediate-,
      and high-risk PCa treated with brachytherapy who have no or at least a single
      risk factor for CAD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study
      cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA]
      <10 ng/ml, Gleason score 6, and clinical stage T1-T2a); 4365 men with
      intermediate-risk PCa (PSA 10-20 ng/ml or Gleason score <8 or clinical stage
      <T3); and 1360 men with localized or locally advanced, high-risk PCa
      consecutively treated in a community-based, multi-institutional setting between
      1991 and 2006. CAD risk factors included at least a history of diabetes mellitus,
      hypercholesterolemia, or hypertension. The median follow-up for men with low-,
      intermediate-, and high-risk PCa were 4.1, 4.4, and 4.6 yr, respectively.
      INTERVENTIONS: Men were treated with or without a median duration of 4 mo of NHT
      followed by brachytherapy with or without supplemental external-beam radiation
      therapy (EBRT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression
      multivariable analyses were performed to assess whether NHT use affected the risk
      of ACM in men with low-, intermediate-, and high-risk PCa, adjusting for age;
      year of brachytherapy; supplemental EBRT use; the presence of CAD risk factors;
      treatment propensity score; and known PCa prognostic factors, including
      pretreatment PSA level, biopsy Gleason score, and clinical stage. RESULTS AND
      LIMITATIONS: NHT use was associated with a significantly increased risk of ACM in
      men with low-risk PCa (adjusted hazard ratio [HR]: 1.27; 95% confidence interval
      [CI], 1.07-1.51; p<0.01) but not in men with intermediate-risk (adjusted HR:
      1.13; 95% CI, 0.96-1.35; p=0.15) or high-risk PCa (adjusted HR: 0.86; 95% CI,
      0.66-1.13; p=0.28). Using an interaction model for the low-risk group, NHT use
      was associated with a significantly increased risk of ACM in the subgroup of men
      with at least a single CAD risk factor (adjusted HR: 1.36; 95% CI, 1.07-1.74;
      p=0.01) but not for men with no CAD risk factors (adjusted HR: 1.19; 95% CI, 0.95
      1.51; p=0.13). CONCLUSIONS: For men with no or at least a single risk factor for
      CAD, NHT use is associated with an increased risk of ACM in the setting of low
      risk but not intermediate- or high-risk PCa. This effect is driven by the
      subgroup of men with at least a single risk factor for CAD. These results warrant
      prospective validation given the widespread use of NHT for prostate downsizing
      prior to brachytherapy.

PMID- 22981137
TI  - Hepatic glucose production pathways after three days of a high-fat diet.
AB  - OBJECTIVE: A three-day high-fat diet induces hepatic steatosis and hepatic
      insulin resistance in rats without altering fasting plasma glucose concentration
      or the rate of glucose production. However, as the nutrient profile available to
      the liver is substantially altered by a high-fat diet, we hypothesized that the
      relative fluxes supporting hepatic glucose production would be altered.
      MATERIALS/METHODS: To test this hypothesis, we used multiple tracers ([3,4
      (13)C(2)]glucose, (2)H(2)O, and [U-(13)C(3)]propionate) followed by NMR analysis
      of blood glucose to quantify net glucose production and the contributions of
      glycogen and key gluconeogenesis precursors in 4-5-h fasted rats. RESULTS: NMR
      analysis demonstrated that the majority of blood glucose was derived from
      glycogen and the citric acid cycle, while a smaller fraction of glucose was
      derived from glycerol in both controls and high-fat-fed animals. High-fat feeding
      was associated with a two-fold increase in plasma glycerol concentration and an
      increase in the contribution (both fractional and absolute) of glycerol
      gluconeogenesis. The increase in gluconeogenesis from glycerol tended to be
      balanced by a decrease in glycogenolysis. The absolute fluxes associated with the
      citric acid cycle including gluconeogenesis from the cycle intermediates,
      pyruvate cycling and the citric acid cycle flux itself, were not altered by this
      short high-fat diet. CONCLUSIONS: A short term high-fat diet altered the specific
      pathways for hepatic glucose production without influencing the overall rate of
      glucose production or flux in the citric acid cycle.

PMID- 22981139
TI  - Acute superior vena cava syndrome after rupture of Kommerell's diverticulum: a
      case report.
AB  - Kommerell's diverticulum, a rare congenital aortic anomaly, is dilatation at the
      region in which an aberrant subclavian artery branches from either a left-sided
      or right-sided thoracic aorta. We report a rare case of acute superior vena cava
      syndrome that developed in a young healthy male patient who presented to the
      emergency department in imminent respiratory arrest after rupture of this
      diverticulum.

PMID- 22981138
TI  - Do fluids facilitate stone passage in acute ureteral colic?

PMID- 22981140
TI  - [Dynamic magnetic resonance imaging in the diagnosis of tumors and pseudotumors
      of the musculoskeletal system].
AB  - The greater temporal resolution provided in ultrafast dynamic contrast-enhanced
      magnetic resonance imaging sequences makes it possible to know the physiological
      phenomenon of the distribution of the contrast material through a time-signal
      intensity curve. Analyzing these curves enables us to deduce information relevant
      to the vascularization and perfusion of tissues, capillary permeability, and the
      interstitial space in the tumor. A steep curve with early washout in a space
      occupying lesion greatly increases the possibility of histological malignancy,
      although this type of curve is not rare in benign lesions and relatively flat
      curves are not rare in malignant tumors. Nevertheless, dynamic studies of the
      uptake of contrast material provide important information for the
      characterization of neoplasms that, together with the usual signs, can help to
      differentiate between benign and malignant tumors of adipocyte, chondroid, or
      neural lineage, clearing up diagnostic uncertainty in certain benign lesions such
      as osteoid osteoma and ischemic musculoskeletal disease. Furthermore, it enables
      the accurate determination of the response to chemotherapy, detecting recurrence
      within the treated tumor early, delimiting more precisely the margins between the
      tumor and peritumoral edema, and helping in diagnostic planning by determining
      the most vascularized areas of the tumor, which are more likely to be malignant.

PMID- 22981141
TI  - Working together in placing the long term interests of the child at the heart of
      the DSD evaluation.
AB  - This paper articulates a number of important but often ignored questions that
      families have during and following the diagnosis of a child with a DSD.
      Recounting a personal birth experience, it illustrates the urgent need for more
      psychological and educational support during and following diagnosis and gender
      assignment. Finally, the paper describes some practical strategies for raising a
      child living with genital difference. It urges everyone involved in the care of
      children with a DSD to support parents in looking beyond initial anxiety and
      worry and always to place the child's long term wellbeing at the very heart of
      the clinical decision-making and care.

PMID- 22981142
TI  - Utilization of computer enhanced visual learning (CEVL) method improves
      endoscopic diagnosis of posterior urethral valves (PUV).
AB  - INTRODUCTION: Training in urology relies largely on the traditional methods of
      clinical immersion and the use of reference texts. Computer enhanced visual
      learning (CEVL) is an on-line learning tool that may effectively supplement these
      methods. We evaluate the role of CEVL in establishing the endoscopic diagnosis of
      posterior urethral valves (PUV). MATERIAL AND METHODS: This study compares test
      scores of PUV diagnosis made by pediatric urologists and fellows in pediatric
      urology training programs while watching pediatric cystourethroscopy videos
      before and after viewing the CEVL learning module. The CEVL module used
      illustrations and video clips to highlight criteria important in diagnosing PUV.
      Data was analyzed for improvement in test scores (Chi square). RESULTS: There
      were 112 study subjects enrolled. An improvement in the post-test scores was
      observed (p < 0.001). When independently analyzing cases with PUV, an improvement
      in diagnosis was also observed (p < 0.005). While a trend toward improvement was
      observed in correctly diagnosing normal urethras, this was not statistically
      significant. CONCLUSION: Overall, there was an improvement observed after viewing
      the CEVL module. This was most notable in cases where PUV was present. The CEVL
      module is an effective supplement for enhancing the endoscopic diagnosis of PUV.

PMID- 22981143
TI  - Model-based drug approval - the rubber hits the road.

PMID- 22981144
TI  - Comment on the report "limitations of model-based dose selection for indacaterol
      in patients with chronic obstructive pulmonary disease".

PMID- 22981146
TI  - Modeling of the LDL cholesterol-lowering effect of atorvastatin in Korean
      dyslipidemic patients and non-patient volunteers.
AB  - OBJECTIVE: The aim of this study was to develop a longitudinal pharmacodynamic
      model describing the time-courses of low-density lipoprotein cholesterol (LDL)
      profiles during and after atorvastatin treatment in Korean dyslipidemic patients
      and non-patient volunteers. METHODS: 15 dyslipidemic patients and 11 non-patient
      volunteers with no prior therapy participated in a parallel, 2-step dose
      escalation study. Subjects received atorvastatin doses ranging from 10 to 80 mg
      for 42 days (dyslipidemic patients) or 10 mg for 21 days (non-patient
      volunteers). Plasma samples were collected before and during the treatment period
      and up to 2 weeks after the last administration. A population pharmacodynamic
      model was built using the NONMEM software package. An indirect response model
      consisting of production in hepatocyte and elimination from plasma stimulated by
      atorvastatin described the LDL time-course. RESULTS: The typical population value
      of the estimated dose producing 50% of maximal stimulation on LDL elimination
      (SD50) for dyslipidemic patients was 11.9 mg, which was about 6 times higher than
      that of non-patient volunteers (2.0 mg). CONCLUSION: A longitudinal population
      pharmacodynamic model for the LDL-lowering effect of atorvastatin in both
      dyslipidemic patients and non-patient volunteers was developed. This could help
      guide optimal therapies according to the target population.

PMID- 22981147
TI  - Pharmacokinetic comparison of the maleate and free base formulations of LB80380,
      a novel nucleotide analog, in healthy male volunteers.
AB  - OBJECTIVE: LB80380, a dipivoxil ester prodrug of LB80331, is a novel antiviral
      agent for the treatment of chronic hepatitis B. The aim of this study was to
      compare the pharmacokinetic differences after single oral administrations of the
      free base and maleate formulations of LB80380 in healthy male subjects. METHODS:
      An open-label, single- dose, randomized-sequence, 2-treatment crossover study was
      conducted in 32 Korean male volunteers. Subjects received either a combination of
      60 and 90 mg tablets of the free base LB80380 formulation or a 183 mg (150 mg as
      a free base) tablet of the maleate LB80380 formulation. Then, after a 14- day
      washout period, each subject received the other formulation. Plasma and urine
      concentrations of LB80331 and LB80317 (active metabolites of LB80380) were
      measured by validated liquid chromatographytandem mass spectrometry assays. A
      safety assessment, which included vital signs, adverse events, electrocardiograms
      and clinical laboratory tests, was performed for each subject. RESULTS: A total
      of 32 healthy subjects was enrolled, and 26 subjects completed the study. Single
      oral administrations of LB80380 maleate tablets did not result in clinically
      significant differences in the safety profile compared to the LB80380 free base
      tablets. The 90% confidence intervals (CIs) for the geometric mean ratios of Cmax
      and AUClast for LB80331 of the two treatments (maleate versus free base
      formulation) were 0.986 - 1.1240 and 0.9848 - 1.0533, respectively. The 90% CIs
      for the geometric mean ratios of Cmax and AUClast for LB80317 were 0.8379 -
      0.9696 and 0.7224 - 0.9196. CONCLUSIONS: In healthy male subjects, the 183 mg
      LB80380 maleate tablet was pharmacokinetically equivalent to the 60 and 90 mg
      LB80380 free base tablets.

PMID- 22981148
TI  - Urinary MCP-1 and RBP: independent predictors of renal outcome in
      macroalbuminuric diabetic nephropathy.
AB  - BACKGROUND: Albuminuria has been considered a sine qua non condition for the
      diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate
      outcome of chronic kidney disease (CKD). However, recent data suggest that
      albuminuria may fail as a biomarker in a subset of patients, and the search for
      novel markers is intense. METHODS: We analyzed the role of urinary RBP and of
      serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk
      of dialysis, doubling of serum creatinine or death (primary outcome, PO) in 56
      type 2 diabetic patients with macroalbuminuric DN. RESULTS: Mean follow-up time
      was 30.7+/-10 months. Urinary RBP and MCP-1 were significantly higher in patients
      presenting the PO, whereas no difference was shown for TGF-beta or VEGF. In the
      Cox regression, urinary RBP, MCP-1 and VEGF were positively associated and serum
      VEGF was inversely related to the risk of the PO. However, after adjustments for
      creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6;
      95% CI 2.7-49.2, p=0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6
      76.4, p=0.02 for log MCP-1) remained as significant independent predictors of the
      PO. CONCLUSION: Urinary RBP and MCP-1 are independently related to the risk of
      CKD progression in patients with macroalbuminuric DN. Whether these biomarkers
      have a role in the setting of normoalbuminuria and microalbuminuria in DN should
      be further investigated.

PMID- 22981149
TI  - Prevalence of abnormal gastric emptying in asymptomatic women with newly detected
      diabetes and its reversibility after glycemic control-a prospective case control
      study.
AB  - OBJECTIVE: Effects of systemic hyperglycemia and normoglycemia on gastric
      emptying in people with type 2 diabetes are not clear. The aim of the study was
      to investigate the gastric emptying time in people with newly detected diabetes
      before and after control of diabetes compared with healthy controls. METHODS:
      Gastric emptying to solid meal was studied in 30 asymptomatic women with newly
      detected diabetes before and after achieving euglycemia and compared with 20
      healthy age, sex and weight matched controls using egg white labelled with
      Technetium 99m Sulfur Colloid. RESULTS: Delayed gastric emptying was seen in 90%
      of women with diabetes and none in healthy controls. Lag phase was 83.1+/-11.8
      min in cases compared to 37.2+/-4.0 in controls (p=0.05). Gastric emptying at 4h
      was 46.73%+/-4.84% in cases and 97.65%+/-0.59% in controls (p=0.05).T50 was 250+/
      8.8 min in cases against 94.70+/-5.10 min in controls (p<0.05). After control of
      diabetes, lag phase normalized to 37.2+/-4.0 min against 35.2+/-4.6 min in
      controls. Similarly all other parameters also normalized after control of
      diabetes. CONCLUSIONS: Delayed gastric emptying to solids was seen in 90% of
      women with type 2 diabetes at the time of hyperglycemia and normalized after
      control of diabetes.

PMID- 22981150
TI  - Riga-fede disease: a case report.

PMID- 22981151
TI  - Condom availability in middle schools: evidence and recommendations.

PMID- 22981152
TI  - A preliminary examination of the specificity of the functions of nonsuicidal self
      injury among a sample of university students.
AB  - To examine whether individuals who engage in NSSI report different coping
      behaviors and regulatory needs compared to a non-injuring comparison group, we
      surveyed 1107 undergraduates using a Functions Index. Individuals who engaged in
      NSSI indicated greater use of coping behaviors for anti-dissociation,
      interpersonal influence, and self-punishment than the non-NSSI group.

PMID- 22981153
TI  - No effect of polymorphisms in the non-duplicated region of the CHRNA7 gene on
      sensory gating P50 ratios in patients with schizophrenia and bipolar disorder.
AB  - Previous research has reported that bipolar disorder and schizophrenic patients
      evidence sensory gating deficits. The use of intermediate phenotypes may
      facilitate genetic studies. Four single nucleotide polymorphisms (SNPs) located
      on the non-duplicated region of the alpha-7 nicotinic receptor gene (CHRNA7) were
      genotyped in 95 healthy subjects, 127 bipolar disorder and 153 schizophrenic
      patients. We evaluated the association of these polymorphisms with P50 evoked
      potential measures. Our results do not support a role for the candidate gene in
      this neurophysiological disturbance.

PMID- 22981154
TI  - Impaired theory of mind but intact decision-making in Asperger syndrome:
      implications for the relationship between these cognitive domains.
AB  - The relationship between decision making and theory of mind (TOM) has been hardly
      investigated in patients with asperger syndrome (AS). Here, we show that the AS
      group (n=25) exhibited deficits on a complex TOM task, yet were unimpaired in a
      decision-making test. No association was found between these two domains.

PMID- 22981155
TI  - No genetic evidence for Neuregulin 3 conferring risk of schizophrenia in the
      Chinese population.
AB  - We genotyped 13 single nucleotide polymorphisms (SNPs) within Neuregulin 3 (NRG3)
      to investigate the association between NRG3 and schizophrenia in 488 patients and
      506 controls in Northwest China. No association was detected either in SNPs or in
      haplotypes. Our study provided no evidence that NRG3 confers a risk of
      schizophrenia susceptibility in the Han Chinese population.

PMID- 22981156
TI  - Differences in trauma and posttraumatic stress symptoms in clients with
      schizophrenia spectrum and major mood disorders.
AB  - The current study of 371 community mental health clients with severe mental
      illness examined differences in frequency of common lifetime trauma and other
      stressful events in clients with schizophrenia spectrum and major mood disorders
      in order to gauge the unique variance in posttraumatic stress symptoms explained
      by trauma/stressful events when controlling for other psychiatric measures. The
      overwhelming majority (88.1%) of these clients reported at least one
      stressful/traumatic event in their lifetime with a median of seven such events.
      Regression modeling revealed that physical abuse was uniquely predictive of
      posttraumatic stress symptoms when controlling for gender, psychiatric symptoms,
      and other problems in functioning. Suggestions for future trauma research include
      measuring multiple types and frequencies of traumatic events, including "non
      criterion A" stressors, and controlling for other psychiatric symptoms and
      indicators of psychosocial functioning in order to better isolate the unique
      effects of trauma. Limitations of the study include the lack of a structured
      interview schedule for diagnosis and the cross sectional design.

PMID- 22981158
TI  - The specific VPAC2 agonist Bay 55-9837 increases neuronal damage and hemorrhagic
      transformation after stroke in type 2 diabetic rats.
AB  - VPAC2 receptor is a potential target for the treatment of type 2 diabetes and may
      also convey neuroprotective effects. The aim of this study was to determine the
      potential efficacy of the VPAC2 receptor agonist Bay 55-9837 against stroke in
      type-2 diabetic Goto-Kakizaki (GK) rats. GK rats were treated intravenously once
      daily for 7 days with 0.25 or 0.025 nmol/kg Bay 55-9837 or vehicle before
      inducing stroke by transient middle cerebral artery occlusion. Treatments were
      then continued for 7 further days. The glycemic effects of Bay 55-9837 were
      assessed by measuring fasting blood glucose and oral glucose tolerance. The
      severity of stroke was measured by assessing ischemic volume. The results show
      that Bay 55-9837 is not effective in lowering fasting glycemia and does not
      facilitate glucose disposal. The highest dose of Bay 55-9837 (0.25 nmol/kg) led
      to increased mortality and brain hemorrhage when compared to control. The lower
      dose of Bay 55-9837 (0.025 nmol/kg) did not increase mortality rate but caused a
      threefold increase of the ischemic lesion size with signs of brain hemorrhages as
      compared to control. In conclusion, Bay 55-9837 did not show antidiabetic or
      antistroke efficacy in the type 2 diabetic GK rat. Contrarily, Bay 55-9837
      treatment led to increased mortality and worsening of the severity of stroke.

PMID- 22981157
TI  - A synthetic five amino acid propeptide increases dopamine neuron differentiation
      and neurochemical function.
AB  - A major consequence of Parkinson's disease (PD) involves the loss of dopaminergic
      neurons in the substantia nigra (SN) and a subsequent loss of dopamine (DA) in
      the striatum. We have shown that glial cell line-derived neurotrophic factor
      (GDNF) shows robust restorative and protective effects for DA neurons in rats,
      non-human primates and possibly in humans. Despite GDNF's therapeutic potential,
      its clinical value has been questioned due to its limited diffusion to target
      areas from its large size and chemical structure. Several comparatively smaller
      peptides are thought to be generated from the prosequence. A five amino-acid
      peptide, dopamine neuron stimulating peptide-5 (DNSP-5), has been proposed to
      demonstrate biological activity relevant to neurodegenerative disease. We tested
      the in vitro effects of DNSP-5 in primary dopaminergic neurons dissected from the
      ventral mesencephalon of E14 Sprague Dawley rat fetuses. Cells were treated with
      several doses (0.03, 0.1, 1.0, 10.0 ng/mL) of GDNF, DNSP-5, or an equivalent
      volume of citrate buffer (vehicle). Morphological features of tyrosine
      hydroxylase positive neurons were quantified for each dose. DNSP-5 significantly
      increased (p < 0.001) all differentiation parameters compared to citrate vehicle
      (at one or more dose). For in vivo studies, a unilateral DNSP-5 treatment (30
      MUg) was administered directly to the SN. Microdialysis in the ipsilateral
      striatum was performed 28 days after treatment to determine extracellular levels
      of DA and its primary metabolites (3,4-dihydroxyphenylacetic acid and
      homovanillic acid). A single treatment significantly increased (~66%)
      extracellular DA levels compared to vehicle, while DA metabolites were unchanged.
      Finally, the protective effects of DNSP-5 against staurosporine-induced
      cytotoxicity were investigated in a neuronal cell line showing substantial
      protection by DNSP-5. Altogether, these studies strongly indicate biological
      activity of DNSP-5 and suggest that DNSP-5 has neurotrophic-like properties that
      may be relevant to the treatment of neurodegenerative diseases like PD.

PMID- 22981159
TI  - Intracellular mechanisms coupled to NPY Y2 and Y5 receptor activation and lipid
      accumulation in murine adipocytes.
AB  - The formation of adipose tissue is a process that includes the pre-adipocyte
      proliferation and differentiation to adipocytes that are cells specialized in
      lipid accumulation. The adipocyte differentiation is a process driven by the
      coordinated expression of various transcription factors, such as peroxisome
      proliferator-activated receptor (PPAR-gamma). Neuropeptide Y (NPY) induces
      adipocyte proliferation and differentiation but the NPY receptors and the
      intracellular pathways involved in these processes are still not clear. In the
      present work we studied the role of NPY receptors and the intracellular pathways
      involved in the stimulatory effect of NPY on lipid accumulation. The murine pre
      adipocyte cell line, 3T3-L1, was used as a cell model. Adipogenesis was evaluated
      by quantifying lipid accumulation by Oil red-O assay and by analyzing PPAR-gamma
      expression using the Western blotting assay. Adipocytes were incubated with NPY
      (100nM) and a decrease on lipid accumulation and PPAR-gamma expression was
      observed in the presence of NPY Y(2) receptor antagonist (BIIE0246, 1MUM) or NPY
      Y(5) antagonist. Furthermore, NPY Y(2) (NPY(3-36), 100nM) or NPY Y(5) (NPY(19
      23)(GLY(1), Ser(3), Gln(4), Thr(6), Ala(31), Aib(32), Gln(34)) PP, 100nM)
      receptor agonists increased lipid accumulation and PPAR-gamma expression. We
      further investigate the intracellular pathways associated with NPY Y(2) and NPY
      Y(5) receptor activation. Our results show NPY induces PPAR-gamma expression and
      lipid accumulation through NPY Y(2) and NPY Y(5) receptors activation. PKC and
      PLC inhibitors inhibit lipid accumulation induced by NPY Y(5) receptor agonist.
      Moreover, our results suggest that lipid accumulation induced by NPY Y(2)
      receptor activation occurs through PKA, MAPK and PI3K pathways. In conclusion,
      this study contributes to a step forward on the knowledge of intracellular
      mechanisms associated with NPY receptors activation on adipocytes and contributes
      to a better understanding and the development of new therapeutic targets for
      obesity treatment.

PMID- 22981160
TI  - [Chronic central nervous system effects of pesticides: state-of-the-art].
AB  - BACKGROUND: Given the neurotoxic properties of pesticides, suggested by
      experimental results and clinical observations, many epidemiological studies have
      investigated neurological effects following acute or chronic exposure to
      pesticides. This review provides an overview of current knowledge about pesticide
      effects on the central nervous system: neurodegenerative diseases (Alzheimer's
      disease, Parkinson's disease, amyotrophic lateral sclerosis), cognitive
      disorders, and psychiatric disorders (mood disorders, anxiety, depression and
      suicide). RESULTS: Parkinson's disease, the most widely studied in relation with
      pesticide exposure, particularly with insecticides and herbicides, was observed
      to be a risk factor of the disease. Evidence is scarce for Alzheimer's disease
      and amyotrophic lateral sclerosis, but quite consistent. Cognitive and
      psychiatric disorders were often observed in relation with organophosphate
      insecticide exposure. Cognitive disorders were found associated with acute and
      chronic exposures, and psychiatric disorders mostly with poisonings. These
      epidemiologic studies were limited by a lack of detailed and reliable exposure
      assessment. The role of genetic susceptibilities has been recently observed, but
      must be further investigated.

PMID- 22981161
TI  - Do perinatal guidelines have an impact on obstetric practices?
AB  - BACKGROUND: The publication of several sets of French guidelines was
      unfortunately not accompanied by planned assessment of their impact on practices.
      The goal of this study was to assess the impact of eight French perinatal
      guidelines on actual obstetric practices. METHODS: Historical cohort setting in
      France: the Audipog database of 299,412 pregnancies from 1994 to 2006, from which
      we extracted a sub-sample by randomLy selecting from each participating maternity
      ward all births occurring during a single month of each year (n=107,450
      pregnancies). The main outcome measure was the incidence of pertinent perinatal
      indicators related to these guidelines. These included site of delivery for low
      birth-weight infants (1998), caesarean delivery (2000), preterm delivery (2002),
      breastfeeding (2002), smoking and pregnancy (2004), immediate postpartum
      hemorrhages (2004), early discharge after delivery (2004) and episiotomies
      (2005). Standardised rates, before and after the year of each guideline, were
      compared using a Chi(2) test. RESULTS: The percentage of children weighing less
      than 1500 g at birth born in Level III hospitals increased through 1999 but
      dropped subsequently, without ever returning to the 1994 level (P<0.0001). The
      overall caesarean rate climbed slowly but regularly from 1994 through 2006
      (P<0.0001). Use of antenatal corticosteroids for women hospitalised for
      threatened preterm labour and in children born before 33 weeks has fluctuated
      since the release of the guideline (P>0.05). Exclusive breastfeeding at discharge
      from the maternity ward has increased slowly (P<0.0001). The percentage of
      deliveries with active management of the third stage of labour rose notably from
      1999 to 2006 (P<0.0001), and smoking cessation during pregnancy rose slightly in
      2006 (P<0.0001). Since 1994, early discharges have become slowly, slightly, but
      regularly more frequent for all women (P<0.0001). The guideline on episiotomies
      has had a slight positive effect in the short term (P<0.0001). CONCLUSIONS:
      Globally, the impact on actual practices of clinical practice guidelines, except
      the guideline concerning the active management of the third stage of labour, was
      low. Most of the changes observed in practices began before the pertinent
      guideline was published.

PMID- 22981163
TI  - Erased markings on multiple flexible epidural catheters.

PMID- 22981162
TI  - The Xpert(r) MTB/RIF assay evaluation in South Korea, a country with an
      intermediate tuberculosis burden.
AB  - SETTING: A central hospital laboratory in South Korea. OBJECTIVE: To evaluate the
      usefulness of the Xpert(r) MTB/RIF assay in a country with an intermediate
      tuberculosis burden. DESIGN: A total of 71 real-time polymerase chain reaction
      positive sputum sediments were tested within  24 h by the Xpert MTB/RIF assay.
      Mycobacterium tuberculosis detection was compared with smear microscopy and
      culture. Rifampicin (RMP) resistance was compared with a culture-based method and
      rpoB gene sequencing. We also assessed the limit of detection for mutant
      proportions  and time savings in diagnosis. RESULTS: The Xpert MTB/RIF assay
      detected M. tuberculosis in 71 (100%) specimens (32 smear-positive, 39 smear
      negative). This assay showed 100% (62/62) concordance with drug resistance
      confirmed by culture and 98.4% (61/62) concordance with sequencing.  A specimen
      containing approximately 50% of mutant p.His526Tyr was falsely interpreted as
      wild-type bacilli by this assay. The minimal detection ratio was 5:1 of mutant
      vs. wild-type cells. The median time saved was 18.5 days (range 9-30) for the
      diagnosis of M. tuberculosis and  81.5 days (65-136) for RMP susceptibility in
      smear-negative, culture-positive patients. CONCLUSIONS: The Xpert MTB/RIF assay
      showed high sensitivity in detecting M. tuberculosis with information on RMP
      resistance, and had a more rapid time to diagnosis compared to conventional 
      tests; however, the location and amount of mutation may affect test sensitivity.

PMID- 22981164
TI  - The effect of glove material upon the transfer of methicillin-resistant
      Staphylococcus aureus to and from a gloved hand.
AB  - BACKGROUND: Although disposable gloves can protect the hands of a health care
      worker from acquiring bacteria, during patient care the glove surface itself can
      become heavily contaminated making cross transmission via contaminated gloved
      hands likely. The aim of this study was to determine whether the type of glove
      worn by health care workers could influence the spread of methicillin-resistant
      Staphylococcus aureus (MRSA). METHODS: Laboratory studies were conducted to
      assess the ease with which MRSA was transferred between different types of glove
      and surfaces likely to be found within the ward environment. RESULTS: In the
      absence of simulated body fluid, mean bacterial transfer to and from the
      different gloves ranged from 0.1% to 16% and from 0.01% to 19.5%, respectively.
      Glove material and glove hydrophobicity were identified as the 2 most important
      factors influencing bacterial transfer. Nitrile gloves were associated with the
      lowest transfer rates. The highest numbers of bacteria were transferred to and
      from the most hydrophilic and most hydrophobic glove, respectively. The
      adsorption of simulated body fluids altered the physiochemical properties of the
      gloves. Bacterial transfer significantly increased and was similar to and from
      all glove types. CONCLUSION: Disposable glove type can affect cross-contamination
      rates among patient, health care worker, and environment. Nonetheless, choice of
      glove should be considered less important than the correct use of gloves and
      proper hand hygiene.

PMID- 22981165
TI  - Knowledge, attitudes and practice regarding Clostridium difficile: a survey of
      physicians in an academic medical center.
AB  - Using current guidelines, we surveyed physicians at our hospital to ascertain
      knowledge, attitudes, and practice regarding Clostridium difficile infection. The
      survey identified significant gaps in knowledge and practice. Infection control
      professionals should include physician education on Clostridium difficile
      infection diagnosis, isolation precautions, and treatment as part of a
      comprehensive control program.

PMID- 22981167
TI  - Characterization of NaTaO3 synthesized by ultrasonic method.
AB  - NaTaO(3) perovskite-like materials were synthesized using sodium acetate and
      tantalum ethoxide as precursors in an ultrasonic bath at room temperature. The
      pristine sample was thermally treated at 600  degrees C and characterized using
      XRD, N(2) physisorption, DRS, SEM and TEM techniques. The structural
      characterization by X-ray powder diffraction revealed that the crystallization of
      the NaTaO(3) phase prepared at 600  degrees C showed agglomerates sizes in the
      micrometric scale, as confirmed by scanning electron microscopy (SEM). On the
      other hand, well-defined NaTaO(3) particles in the nanometric scale were
      determined using TEM. It was found that, for the treated sample, the band gap and
      BET area was 3.8 eV and 9.5m(2) g(-1), respectively. The annealed perovskite,
      deposited onto ITO glass, presented an important variation in the open circuit
      potential transient during UV light irradiation in neutral solution, compared
      with its counterpart prepared by solid-state method. These intrinsic properties,
      given by the preparation route, might be appropriate for increase its
      photocatalytic activity.

PMID- 22981166
TI  - Endogenous androgen deficiency enhances diet-induced hypercholesterolemia and
      atherosclerosis in low-density lipoprotein receptor-deficient mice.
AB  - BACKGROUND: Despite numerous clinical and animal studies, the role of sex steroid
      hormones on lipoprotein metabolism and atherosclerosis remain controversial.
      OBJECTIVE: We sought to determine the effects of endogenous estrogen and
      testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat
      diet with no added cholesterol. METHODS: Male and female low-density lipoprotein
      receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from
      fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were
      performed to evaluate the effects of the presence or absence of endogenous
      hormones on lipid levels, lipoprotein distribution, and atherosclerosis
      development. RESULTS: Female mice fed the study diet for 17 weeks had a marked
      increase in levels of total cholesterol, triglycerides, apolipoprotein-B
      containing lipoproteins, and atherosclerosis compared with male mice.
      Surprisingly, ovariectomy in female mice had no effect on any of these
      parameters. In contrast, castration of male mice markedly increased total
      cholesterol concentrations, triglycerides, apolipoprotein B-containing
      lipoproteins, and atherosclerotic lesion formation compared with male and female
      mice. CONCLUSIONS: These data suggest that endogenous androgens protect against
      diet-induced increases in cholesterol concentrations, formation of proatherogenic
      lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy,
      which decreases androgen concentrations, promotes increases in cholesterol
      concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion
      formation in low-density lipoprotein receptor-deficient mice in response to a low
      fat diet.

PMID- 22981168
TI  - Aldosterone synergizes with peripheral inflammation to induce brain IL-1beta
      expression and depressive-like effects.
AB  - Recent findings have shown that the physiological functions of the hormone
      aldosterone go far beyond its well-known role in blood-pressure regulation and
      salt/water homeostasis. Aldosterone is for example involved in the regulation of
      inflammation, and also binds directly to mineralocorticoid receptors in specific
      brain regions. Interestingly, depressive symptoms appear to correlate with
      alterations of the aldosterone system but the underlying mechanisms have not been
      elucidated. In this study aldosterone (2 MUg/100g body weight/day) was
      continuously administered via osmotic minipumps for 5 days. Lipopolysaccharide
      (LPS) was administered once a day for 5 days in a dose of 1mg/kg ip. The rats
      were tested for depressive-like behavior 24h after the last LPS injection.
      Protein levels of cytokines were measured in serum and cerebrospinal fluid (CSF).
      mRNA expression of interleukin (IL)-1beta and IL-6 in the prefrontal cortex (PFC)
      was analyzed using reverse transcriptase qPCR. We found that aldosterone
      treatment increased LPS-induced IL-1beta mRNA expression in the PFC and CSF.
      Moreover, there was a positive correlation between IL-1beta in CSF and depressive
      like behaviors. These findings suggest that IL-1beta is affected by the renin
      aldosterone-angiotensin system (RAAS) activity and connected to symptoms of
      depression.

PMID- 22981169
TI  - Inositol 1,4,5-trisphosphate 3-kinase B (Itpkb) controls survival, proliferation
      and cytokine production in mouse peripheral T cells.
AB  - Mice genetically-deficient for the B isoform of the inositol 1,4,5-trisphosphate
      3-kinase (or Itpkb) have a severe defect in thymocytes differentiation and thus
      lack peripheral T cells. In order to study the functional role of Itpkb in
      peripheral T cells, we constructed a new mouse where a transgene encoding mouse
      Itpkb is specifically and transiently expressed in thymocytes of Itpkb(-)(/)(-)
      mice. This allows a partial rescue of mature thymocyte/T cell differentiation and
      thus the functional characterization of peripheral T cells lacking Itpkb. We show
      here that Itpkb(-)(/)(-) CD4(+) and CD8(+) peripheral T cells present important
      functional alterations. Indeed, an increased activated/memory phenotype as well
      as a decreased proliferative capacity and survival were detected in these T
      cells. These Itpkb-deficient peripheral T cells have also an increased capacity
      to secrete cytokines upon stimulation. Together, our present results define the
      important role of Itpkb in peripheral mature T cell fate and function in mouse,
      suggesting a potential role for Itpkb in autoimmunity.

PMID- 22981170
TI  - Vaccination guidelines for female infertility patients: a committee opinion.
AB  - Encounters for infertility care are opportunities to assess and update
      immunization status. Women of reproductive age are often unaware of their need
      for immunization, their own immunization status, and the potentially serious
      consequences of preventable disease on pregnancy outcome. The purpose of this
      ASRM Practice Committee document is to summarize current recommendations
      regarding vaccinations for women of reproductive age. This document replaces the
      ASRM Practice Committee document of the same name last published in Fertil Steril
      2008;90:S169-71.

PMID- 22981171
TI  - Intracytoplasmic sperm injection (ICSI) for non-male factor infertility: a
      committee opinion.
AB  - Intracytoplasmic sperm injection, while typically effective for overcoming low or
      absent fertilization in couples with a clear abnormality of semen parameters, is
      frequently utilized in combination with assisted reproductive technologies for
      other etiologies of infertility in the presence of normal semen parameters. This
      committee opinion provides a critical review of the literature, where available,
      to identify situations where this may or may not be of benefit.

PMID- 22981172
TI  - Sorafenib inhibits growth, migration, and angiogenic potential of ectopic
      endometrial mesenchymal stem cells derived from patients with endometriosis.
AB  - OBJECTIVE: To characterize the proliferation, migration, and angiogenic
      properties of mesenchymal stem cells (MSC) from ectopic and eutopic endometrial
      tissue and to investigate the effect of the tyrosine kinase inhibitor sorafenib.
      DESIGN: In vitro studies. SETTING: University hospital and research center.
      PATIENT(S): Patients receiving surgical treatment of endometriosis (n = 4) and
      control patients without endometriosis (n = 2) undergoing surgery for benign
      gynecologic diseases. INTERVENTION(S): Mesenchymal stem cell lines were isolated
      from ectopic and eutopic endometrial tissue, and sorafenib was administered to
      them. MAIN OUTCOME MEASURE(S): Proliferation, migration, invasion of endometrial
      MSC, and expression of ezrin, vascular endothelial growth factor, and hypoxia
      inducible factor-1alpha (HIF-1alpha) were measured. RESULT(S): Ectopic
      endometrial MSC from patients with endometriosis showed a higher proliferation,
      migration, and angiogenic ability than eutopic MSC from the same patient or
      control MSC from patients without endometriosis. Sorafenib reduced the
      proliferation, motility, ezrin phosphorylation, vascular endothelial growth
      factor release, and HIF-1alpha expression of ectopic MSC. CONCLUSION(S): The
      increased proliferative, migratory, and angiogenic phenotype of ectopic MSC may
      be reverted by treatment with sorafenib. Targeting of the MSC population involved
      in sustaining the ectopic lesions might be useful in eradicating endometriotic
      implants.

PMID- 22981173
TI  - Assessment of research quality in major infertility journals.
AB  - OBJECTIVE: To evaluate the level of evidence published in infertility journals
      with the highest impact factors. DESIGN: Systematic review. We searched in PubMed
      identifying potential systematic reviews with meta-analysis (SRs) and randomized
      controlled trials (RCTs) between 2006 and 2010 in the five fertility journals
      with highest impact factor. SETTING: Academic institution. PATIENT(S): None.
      INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Number and proportion of
      potential SRs and RCTs published in 2006-2011, and quality assessment of real
      RCTs published in 2010. RESULT(S): Among evaluated articles, 1.5% and 6.8% were
      SRs and RCTs. Fertility and Sterility has been the journal with more potential
      SRs and RCTs, and Human Reproduction Update was the only one with an increasing
      trend in the number of potential SRs (from 5.3% in 2006 to 24.4% in 2011). Among
      confirmed RCTs, for each quality assessment item, between 50% and 85% were
      classified as having low risk of bias, and the most common high risk of bias was
      related to allocation concealment. Only 23% had a trial registration, which were
      associated with higher quality assessment classifications. Only 10% of RCTs
      reported pharmaceutical industry funding. CONCLUSION(S): This is the first study
      assessing the methodologic quality of publications in the top five fertility
      journals. More than 90% of all the publications were neither SRs nor RCTs. It is
      remarkable that the risk of bias was generally low. Enhancing trial registration
      and funding source statements represent opportunities to improve the quality of
      reporting. We hope this information is useful to researchers, editorial boards,
      and clinicians moving forward with research in our field.

PMID- 22981174
TI  - Allotransplantation of cryopreserved prepubertal mouse ovaries restored puberty
      and fertility without affecting methylation profile of Snrpn-DMR.
AB  - OBJECTIVE: To evaluate the genetic safety of vitrification on the methylation
      imprints and the development and fertility potential of prepubertal mouse
      ovaries. DESIGN: Experimental animal study. SETTING: University-based fertility
      center. ANIMAL(S): Institute of Cancer Research (ICR) 10-day-old female mice, 10
      week-old adult female mice, and 12-week-old adult male mice. INTERVENTION(S):
      Vitrification of juvenile mouse ovaries was performed using ED20 and EG5.5/30
      solutions followed by retrieval of fresh and vitrified-warmed germinal vesicle
      (GV) oocytes for Snrpn differentially methylated regions (DMR) methylation
      analyses, collection of mature oocytes from superovulated ovarian grafts, in
      vitro fertility(IVF), and early embryonic development after heterotopic
      allotransplantation. MAIN OUTCOME MEASURE(S): Analysis of methylation status of
      Snrpn-DMR, percentage of fertilization, and blastocysts formation. RESULT(S):
      Methylation status of Snrpn-DMR from vitrified-warmed GV oocytes did not show
      significant alteration compared with that of controls, although a significant
      reduction of viable oocytes was observed. Puberty as well as endocrine function
      was restored, and no significant difference was shown in number of follicles,
      percentage of mice retaining fertility, and blastocyst formation among three
      groups. CONCLUSION(S): Our study proved that vitrification of prepubertal mouse
      ovaries did not alter the methylation profile of Snrpn-DMR and subsequent
      allotransplantation; IVF could restore the development and fertility potential.

PMID- 22981175
TI  - In search of an efficient injection technique for future clinical application of
      spermatogonial stem cell transplantation: infusion of contrast dyes in isolated
      cadaveric human testes.
AB  - OBJECTIVE: To develop an efficient infusion technique for human spermatogonial
      stem cell transplantation. DESIGN: A mixture with ultrasonic contrast,
      computerized tomography (CT) contrast, and Chinese ink was injected into isolated
      human testes through different sites (the rete testis, the head of the
      epididymis, the deferent duct, and blind testicular infusion). Ultrasound
      transducer was used to visualize the injection site and to observe the flow of
      the mixture injected in the testes. Then, micro-CT scan was used to construct
      three-dimensional images, allowing the calculation of the testicular volume
      filled by the mixture. Finally the efficiency of the infusion was evaluated on
      histologic sections. SETTING: Research laboratory. PATIENT(S): Cadaver testes
      obtained from autopsied bodies at the department of pathology. INTERVENTION(S):
      Ultrasound-guided infusion of contrast liquid. MAIN OUTCOME MEASURE(S): Contrast
      liquid-filled testis volume and presence of ink in seminiferous tubules.
      RESULT(S): Ultrasonography clearly visualized the flow when seminiferous tubules
      were injected from the rete testis. No flow was observed when infusions were made
      either blindly, into the deferent duct, or into the head of the epididymis. On
      micro-CT no significant differences were observed between the different volumes.
      After rete testis infusion, ink particles were found in the lumen of the rete
      testis and in tubules, close and distant from the rete testis. CONCLUSION(S): A
      single ultrasound-guided injection of 800 MUL in the rete testis may provide a
      promising method to transplant human spermatogonial stem cells in a clinical
      setting.

PMID- 22981176
TI  - Child abuse followed by fatal systemic Pseudomonas aeruginosa infection.
AB  - Child abuse has become an increasingly serious diagnostic challenge for
      physicians. The clinical manifestations include malnutrition and sometimes
      infection. In fact, stress in children has been reported to increase
      corticosteroid levels. As a consequence, the thymus begins an involution process,
      producing a severe impairment in cellular and humoral immunity. Here, we report
      the case of a 7-year-old child who suffered a prolonged history of abuse and died
      from a systemic Pseudomonas aeruginosa infection. An initial local chronic
      infection propagated to the pelvic lymph nodes in an immunologically weak body
      and evolved into abscesses/phlegmons of the pelvic tissue, sepsis, acute
      respiratory distress syndrome, multiple organ failure and finally, death. Abused
      children have to be considered as potentially immunologically impaired patients;
      therefore, it is very important to screen them for opportunistic infections.
      Moreover, a history of unusual or recurring infections may indicate abuse,
      especially neglect or malnutrition. In these cases, further investigations should
      be conducted to determine if a protective service case should be opened. Thus,
      there is a need for multidisciplinary cooperation to ensure the early
      identification and prevention of child abuse.

PMID- 22981177
TI  - What younger forensic pathologists need for their training: valuable comments
      from our interviews.

PMID- 22981178
TI  - A one step multiplex PCR assay for rapid screening of East Asian mtDNA
      haplogroups on forensic samples.
AB  - The mitochondrial DNA (mtDNA) haplogroup typing has become an essential tool to
      study human evolutionary history and to infer the matrilineal bio-geographic
      ancestry. In forensic field, the screening of mtDNA haplogroups by genotyping of
      mtDNA single nucleotide polymorphisms (SNPs) can help guarantee the quality of
      mtDNA sequence data as well as can reduce the need to sequence samples that do
      not match. Here, a multiplex mutagenically separated (MS) polymerase chain
      reaction (PCR) system was developed for simultaneous rapid detection of 14 coding
      region SNPs and one deletion motif representing common mtDNA haplogroups of East
      Asia. The multiplex MS PCR system we developed has the advantage of being a one
      step procedure that requires only a single PCR amplification with allele-specific
      primers and allowing straightforward designation of haplogroups along the
      branches of the phylogenetic tree. Therefore, it would be a simple, rapid, and
      reliable detection method useful for large-scale screening of mtDNA variations to
      determine East Asian mtDNA haplogroups.

PMID- 22981179
TI  - Causes of death in forensic autopsy cases of malnourished persons.
AB  - PURPOSE: Medical examiners and forensic pathologists often encounter emaciated
      bodies in postmortem examinations. However, the main disease that caused death is
      often not clear and measures to prevent the unexpected death of malnourished
      persons have not been established. In this study, we examined the underlying
      causes of death among a large number of forensic autopsy cases that showed
      emaciation to clarify the features of sudden, unexpected death in malnourished
      persons. METHODS: Documents of autopsy cases without putrefaction handled during
      2007-2010 by the Tokyo Medical Examiner's Office were reviewed (n=7227). The body
      mass index (BMI) was calculated for each case. The causes of death for cases with
      severe malnutrition (BMI<16; n=885) were closely examined. RESULTS: About 70% of
      all deaths in malnourished cases (BMI<16) was due to disease, and the causative
      diseases are more varied than in those with less severe malnutrition and those
      without malnutrition (BMI?16). A higher proportion of malnutrition as the cause
      of death was observed in younger persons for both sexes, and a higher proportion
      of having a history of psychiatric diseases was observed in younger deceased
      women. In addition, a higher proportion of alcohol-related digestive diseases was
      observed especially in younger men, some of whom had a history of alcohol
      dependence. On the other hand, the proportion of organic diseases, such as
      neoplasms and gastroduodenal ulcer, was higher in older deceased persons,
      especially among men. Around 70% of all respiratory diseases comprised pneumonia
      in both sexes. Among non-disease-related causes of death, poisoning was the most
      frequent cause in women under 55years old (35.3%), with the majority having had a
      history of psychiatric disease. CONCLUSIONS: Because autopsy cases of
      malnourished persons show various causes of death, physicians have to pay more
      attention in making death diagnosis in such cases. From a preventative point of
      view, early detection of organic diseases, a better approach toward managing
      psychiatric diseases, and implementation of vaccination for pneumonia will
      contribute to reduction of future unexpected deaths among malnourished persons.

PMID- 22981180
TI  - Detection of coronary thrombosis after multi-phase postmortem CT-angiography.
AB  - The aim of this study was to compare postmortem angiography-based, autopsy-based
      and histology-based diagnoses of acute coronary thrombosis in a series of
      medicolegal cases that underwent postmortem angiographies according to multiphase
      CT-angiography protocol. Our study included 150 medicolegal cases. All cases
      underwent native CT-scan, postmortem angiography, complete conventional autopsy
      and histological examination of the main organs and coronary arteries. In 10 out
      of the 150 investigated cases, postmortem angiographies revealed coronary
      arterial luminal filling defects and the absence of collateral vessels,
      suggesting acute coronary thromboses. Radiological findings were confirmed by
      autopsy and histological examinations in all cases. In 40 out of 150 cases,
      angiograms revealed complete or incomplete coronary arterial luminal filling
      defects and the presence of collateral vessels. Histological examinations did not
      reveal free-floating or non-adherent thrombi in the coronary arteries in any of
      these cases. Though postmortem angiography examination has not been well
      established for the diagnosis of acute coronary thrombosis, luminal filling
      defects in coronary arteries suggesting acute thromboses can be observed through
      angiography and subsequently confirmed by autopsy and histological examinations.

PMID- 22981181
TI  - How sick is the defendant? Forensic and emergency medical aspects at trial.
AB  - The evaluation of a defendant's ability to stand trial is a core task in the
      field of legal medicine as a supportive instrument of jurisprudence. Before the
      trial, the court-appointed expert informs him-/herself regarding existing somatic
      and psychological illness(-es) within the context of preparing an expert
      evaluation, then composing the written expert evaluation, which reflects the
      condition of the subject at the time of the examination and arrives at an
      assessment of the ability to stand trial. The decompensation or aggravation of
      illnesses - in particular in stressful situations, as is to be expected for the
      defendant in the courtroom - can thus be taken into consideration such that
      alongside the current evaluation of the defendant's health condition, emergency
      medical treatment may also become necessary in court at times. We present three
      case reports about forensic and emergency medical aspects at trial, considering
      how the forensic expert can be able to meet the subsequent challenges.

PMID- 22981182
TI  - Acute pulmonary schistosomiasis in travelers: case report and review of the
      literature.
AB  - We report the case of an American traveler who developed acute pulmonary
      schistosomiasis after swimming in a lake in Madagascar, and we review the
      literature on acute pulmonary schistosomiasis. Schistosomiasis is one of the
      world's most prevalent parasitic diseases, with three species (Schistosoma
      mansoni, Schistosoma haematobium and Schistosoma japonicum) causing the greatest
      burden of disease. Pulmonary manifestations may develop in infected travelers
      from non-endemic areas after their first exposure. The pathophysiology of acute
      pulmonary disease is not well-understood, but is related to immune response,
      particularly via inflammatory cytokines. Diagnosis of schistosomiasis may be
      either through identification of characteristic ova in urine or stool or through
      serology. Anti-inflammatory drugs can provide symptomatic relief; praziquantel,
      the mainstay of chronic schistosomiasis treatment, is likely not effective
      against acute disease; the only reliable prevention remains avoidance of
      contaminated freshwater in endemic areas, as there is no vaccine. Travelers who
      have been exposed to potentially contaminated freshwater in endemic areas should
      seek testing and, if infected, treatment, in order to avoid severe manifestations
      of acute schistosomiasis and prevent complications of chronic disease. Clinicians
      are reminded to elicit a detailed travel and exposure history from their
      patients.

PMID- 22981183
TI  - Should quality measures for lymph node dissection in colon cancer be extrapolated
      to rectal cancer?
AB  - BACKGROUND: A minimum of 12 lymph nodes has been endorsed as a quality measure to
      confirm node-negative colon cancer, but its relevance to early-stage rectal
      cancer is unclear. METHODS: Patients with stage I or II rectal cancer from the
      Surveillance, Epidemiology and End Results tumor registries from 1998 to 2002
      were identified. Patients were grouped by the number of lymph nodes sampled.
      Groups were compared for patient demographics, tumor characteristics, and 5-year
      overall survival. RESULTS: Of the 6,214 patients (57% men) identified, only 33%
      had >=12 lymph nodes examined in the surgical specimen. Multivariate analysis
      identified sex, race, age, T stage, and number of lymph nodes examined as
      independent predictors of 5-year overall survival. CONCLUSIONS: Five-year overall
      survival improved as the number of sampled nodes increased. A thorough
      lymphadenectomy should routinely be performed to optimize staging and to improve
      survival of patients with early-stage rectal cancer.

PMID- 22981184
TI  - Occurrence of seroma after mastectomy: where is the solution?

PMID- 22981185
TI  - LRRK2 G2385R and LRRK2 R1628P increase risk of Parkinson's disease in a Han
      Chinese population from Southern Mainland China.

PMID- 22981186
TI  - Cervical dystonia and genetic common variation in the dopamine pathway.
AB  - Cervical dystonia, a late onset focal dystonia, has a complex genetic background.
      Multiple lines of evidence point to a role for aberrant dopamine levels in
      dystonia. We assessed whether common variation within genes that regulate brain
      dopamine levels and in key genes of the dopamine metabolic pathway, modulate the
      risk for cervical dystonia. DNA was collected from 363 Dutch CD patients and a
      cohort of Dutch control individuals. Haplotype-tagging single nucleotide
      polymorphisms (SNPs) complemented with selected variants of functional importance
      in COMT, DAT, TH, MAO-A and -B, DDC and DBH were investigated. We tested the 143
      markers in single-SNP, haplotype and epistasis analyses. We did not find an
      association with any of the selected 143 SNPs in these key dopamine genes. Our
      data shows that common variations in key genes of the dopamine pathway do not
      contribute to dystonia risk in the Dutch population. Possibly, risk alleles in
      this pathway may be rarer than detectable in this study, or might be located in
      downstream dopamine signaling pathway. Alternatively, found dopamine level
      changes are secondary to the dystonia disease processes.

PMID- 22981187
TI  - [Idiopathic granulomatous mastitis].
AB  - Idiopathic granulomatous mastitis (IGM) is a rare localized granulomatosis of
      unknown aetiology that usually affects women of childbearing age. It often mimics
      breast carcinoma or abscess. Histopathologic evaluation and elimination of the
      others aetiologies of granuloma play a crucial role in the diagnosis. Its
      etiopathogeny remains poorly understood, but Corynebacteria might be involved.
      The disease course is usually protracted, with a significant impact on quality of
      life. The management of IGM remains controversial, but corticosteroids are
      usually the first-line treatment.

PMID- 22981188
TI  - Receptive field characteristics of stretch-insensitive mechanosensitive units in
      the rat urinary bladder.
AB  - INTRODUCTION: The pelvic, hypogastric and pudendal nerves carry sensory
      information from the urinary bladder. The pelvic nerve is reported to be the most
      important one of these afferent nerves in producing urinary bladder sensation.
      The primary types of mechanoreceptors in the bladder can be divided into stretch
      sensitive and stretch-insensitive units. The former is considered to be more
      important in producing bladder sensation. However, little is known about the
      precise receptive field properties of the stretch-insensitive mechanoreceptors in
      the urinary bladder. Therefore, in this study, we systematically investigated the
      receptive field characteristics of the pelvic single unit innervating the rat
      bladder wall. MATERIALS AND METHODS: Functional single unit recordings were made
      from the pelvic nerve afferent filaments of anesthetized rats. A von Frey device
      was used for quantitative mechanical stimulation of the bladder surface. In
      addition, electrical stimulation was used for estimating conduction velocities of
      the nerve fibers in the receptive field. RESULTS: The threshold value for
      mechanical stimulation was statistically lower at the caudal portion of the
      bladder body (sites IV and V) than the other bladder sites. The bladder neck
      (site I) had the highest mechanical stimulation threshold value for the bladder
      stretch-insensitive mechanoreceptors. In most cases, the pelvic nerve had
      bilateral receptive fields. The majority of the pelvic nerve afferents had
      conduction velocities in the slow A-delta or C fiber range. Mechanical
      stimulation threshold values were higher in males than in females in a portion of
      the bladder sites. DISCUSSION: The pelvic stretch-insensitive bladder
      mechanoreceptors are 1) higher threshold at the bladder base, 2) contain large
      bilateral receptive fields and 3) demonstrate relatively slow conduction
      velocities. These characteristics indicate a non-uniform distribution of stretch
      insensitive mechanoreceptors in the rat urinary bladder wall.

PMID- 22981189
TI  - The importance of therapeutic farriery in equine practice.
AB  - For an equine practice to offer therapeutic farriery as a professional service,
      that service must be founded in individual competence and cooperation between
      veterinarian and farrier. Inadequate farriery education and experience may result
      in substandard or even contraindicated therapeutic farriery prescriptions and
      farrier care. Within continuing education for equine practitioners, excellent
      opportunities to advance one's understanding of and clinical competence in
      therapeutic farriery are increasingly available. It is the obligation of the
      veterinarian to acquire and maintain a working understanding of both basic and
      therapeutic farriery to work effectively with the farrier and offer a valid
      service to the client.

PMID- 22981190
TI  - The biomechanics of the equine foot as it pertains to farriery.
AB  - Shoes were originally applied to horses' feet to protect against excessive wear.
      Over the years, countless types of shoes and farriery techniques have been
      developed not only as a therapeutic aid to treat lameness but also to maintain or
      enhance functionality. The past 3 decades have provided equine veterinarians and
      farriers with new information relating to limb biomechanics and the effects of
      various farriery methods. This article describes the principles of foot
      biomechanics and how they are affected by some of the more common farriery and
      shoeing techniques.

PMID- 22981191
TI  - Equine imaging: the framework for applying therapeutic farriery.
AB  - Radiographic evaluation of a horse's foot gives tremendous insight into the
      relationship between the structures within the foot and between the foot and
      distal limb. The information gained from a radiographic study is highly dependent
      on the quality of the radiographs. A systematic approach should be taken when
      planning a radiographic study of the foot. Taking the time to examine the foot
      and prepare it properly will avoid the need, risk, and expense of repeating
      images and will improve the quality and therefore the interpretation of your
      radiographic images. When evaluating the foot for podiatry reasons, it is crucial
      that the positioning of the patient, foot, and x-ray beam be flawless.

PMID- 22981192
TI  - The basics of farriery as a prelude to therapeutic farriery.
AB  - Domesticated horses need hoof care, because it is rare for wear and growth of the
      hooves to be in perfect equilibrium. During the shoeing interval, the hoof grows
      downwards and forward in the direction of the horn tubules, losing some degree of
      angle. Few horses have perfect limb conformation. The shape of a hoof of a limb
      with conformation defects adapts in a predictable way. If, for therapeutic or
      performance reasons, the hoof-shoe combination is modified, there is a not a lot
      of leeway in the trim of a particular foot, whereas the applied shoe type,
      placement, and adjustments provide endless possibilities.

PMID- 22981193
TI  - Therapeutic farriery: one veterinarian's perspective.
AB  - Therapeutic shoeing is best directed at a specific diagnosis, but in the absence
      of a specific diagnosis, it is frequently directed at a symptom. There are only
      so many ways to modify the function of the foot with trimming and shoeing. The
      design of a horse shoe may often be modified to improve one aspect of foot
      function. Modifying a horse shoe to improve one aspect of foot function almost
      invariably impacts another aspect of foot function. The application of horse
      shoes may be based on a specific diagnosis or directed at a symptom. The
      application of shoeing principles is best approached using theoretical reasoning
      based on the research data that are available and experience.

PMID- 22981194
TI  - Farriery for the hoof with low or underrun heels.
AB  - Underrun heels are common and involve hoof capsule distortion in which the horn
      tubules of the heels undergo bending and lengthening, resulting in decreased
      strength and functionality. The syndrome varies in clinical presentation,
      depending on duration, severity of distortion, presence of secondary problems,
      and presence of lameness. Primary treatment goals are to maintain soundness and
      functional integrity of the foot and to establish a normal hoof capsule.
      Resolution of the problem is generally not achieved in horses in a heavy work
      schedule, and realistic goals in this situation are to maintain function,
      alleviate lameness, and arrest progression of the distortion.

PMID- 22981195
TI  - Farriery for the hoof with a high heel or club foot.
AB  - A club foot or flexural deformity may affect a horse at any stage of life from
      neonate through adulthood. The emphasis of this article is on defining and
      recommending the appropriate farriery for flexural deformities involving the deep
      digital flexor tendon and the distal interphalangeal joint. Clinical management
      of the flexural deformity is influenced by the severity, duration, and etiology
      of the club foot as well as the degree and source of lameness. Also discussed is
      the management of mismatched hoof angles, which remains a controversial subject
      for both farrier and veterinarian.

PMID- 22981196
TI  - Farriery for the hoof with a sheared heel.
AB  - Sheared heels develop as an adaptation-distortion of the hoof capsule as a result
      of an abnormal strike and loading pattern of the foot, which is generally a
      consequence of limb conformation. The growth rate around the circumference of the
      hoof should be approximately uniform, but regional disturbances in growth rate
      can occur to either increase or decrease growth. The primary conformational trait
      that is observed in horses that develop sheared heels is a rotational deformity
      of the distal limb and a narrow chest. Farriery is directed toward improving the
      hoof capsule distortion and decreasing the forces on the displaced side of the
      foot.

PMID- 22981197
TI  - Farriery for hoof wall defects: quarter cracks and toe cracks.
AB  - Conditions that result in the loss of the structural integrity of the hoof wall,
      such as quarter and toe cracks, are not uncommon and usually manifest in
      lameness. The successful management of these problems involves identifying and
      addressing the underlying causes, stabilization of the foot, and committed follow
      up.

PMID- 22981198
TI  - Nonseptic diseases associated with the hoof complex: keratoma, white line
      disease, canker, and neoplasia.
AB  - This article addresses nonseptic diseases associated with the hoof complex,
      namely keratoma, white line disease, canker, and neoplasia. Keratoma is an
      uncommon cause of lameness, which may be surgically removed. White line disease,
      a keratolytic process on the solar surface of the hoof, is treated with
      therapeutic farriery and resection of the hoof wall when appropriate. Equine
      canker is an infectious process that results in development of a chronic
      hypertrophy of the horn-producing tissues. Neoplasia involving the equine foot is
      rare, and melanoma is the most common type of neoplasm reported.

PMID- 22981199
TI  - Septic diseases associated with the hoof complex: abscesses, punctures wounds,
      and infection of the lateral cartilage.
AB  - Hoof abscesses are probably the most common cause of acute severe lameness in
      horses encountered by veterinarians and farriers. Most affected horses show
      sudden, severe (acute) lameness; the degree of lameness varies from being subtle
      in the early stages to non-weight bearing. There is still debate between the
      veterinary and farrier professions as to who should treat a hoof abscess and the
      best method to resolve the abscess. Puncture wounds to the sole of the foot can
      introduce bacteria and debris to the solar surface of the distal phalanx and
      produce a fracture or a septic pedal osteitis.

PMID- 22981200
TI  - Treating laminitis: beyond the mechanics of trimming and shoeing.
AB  - Laminitis is typically classified into developmental or prodromal, acute,
      subacute, and chronic phases. Scientific evidence regarding the pathophysiology
      of laminitis does exist, but it is often conflicting and dependent on the
      clinician's interpretation/understanding of the study or the model used for
      inducing laminitis. The diagnosis of laminitis consists of obtaining an accurate
      history, performing a thorough physical examination, and taking good-quality
      radiographs. The use of radiographs for diagnosis and interpretation of laminitis
      is an absolute necessity for the clinician. Laminitis is one disease that
      requires the assembly of a team consisting of the veterinarian, the farrier, and
      the owner to be successfully treated.

PMID- 22981201
TI  - Therapeutic farriery.

PMID- 22981202
TI  - Therapeutic farriery.

PMID- 22981203
TI  - 7-epi-nemorosone from Clusia rosea induces apoptosis, androgen receptor down
      regulation and dysregulation of PSA levels in LNCaP prostate carcinoma cells.
AB  - The aim of this work was to characterize the antitumoral activity of the plant
      compound 7-epi-nemorosone in prostate carcinoma cell lines. Prostate cancer is
      the most frequently diagnosed malignancy and the second-leading cause of cancer
      death in men. In spite of the current therapeutic options for this cancer entity,
      many patients die due to metastases in distant organs and acquired chemotherapy
      resistance. Thus, approaches to provide improvements in outcome and quality of
      life for such patients are urgently needed. Recently, the polyisoprenylated
      benzophenone 7-epi-nemorosone, originally collected by honeybees from Clusia
      rosea and Clusia grandiflora (Clusiaceae), has been described to be a potent
      antitumoral agent. Here, its activity in prostate carcinoma is reported. 7-epi
      nemorosone was isolated from Caribbean propolis employing RP-HPLC techniques. Its
      cytotoxicity was assessed using the MTT proliferation assay in human androgen
      dependent prostate carcinoma LNCaP cells including an MDR1(+) sub-line. No cross
      resistance was detected. FACS-based cell cycle analysis revealed a significant
      increase in the sub-G0/G1, G1, and depletion in the S phase populations. A
      concomitant down-regulation of cyclins D1/D3 and CDK 4/6 in LNCaP cells was
      detected by Western blot. Annexin-V-FITC labeling and caspase-3 cleavage assays
      showed that 7-epi-nemorosone induced apoptotic events. Major signal transduction
      elements such as p38 MAPK and Akt/PKB as well as androgen receptor AR and PSA
      production were found to be down-regulated after exposure to the drug. ERK1/2
      protein levels and phosphorylation status were down-regulated accompanied by up
      regulation but inhibition of the activity of their immediate upstream kinases
      MEK1/2. Additionally, Akt/PKB enzymatic activity was effectively inhibited at a
      similar concentration as for MEK1/2. Here, we demonstrate for the first time that
      7-epi-nemorosone exerts cytotoxicity in an androgen-dependent prostate carcinoma
      entity by targeting the MEK1/2 signal transducer.

PMID- 22981204
TI  - Simultaneous determination of multiple cytokines reveals a pro-inflammatory and
      pro-angiogenic signature after major cardiothoracic surgery: potential role of C
      reactive protein.

PMID- 22981205
TI  - Combining gene expression microarray- and cluster analysis with sequence-based
      predictions to identify regulators of IL-13 in allergy.
AB  - The Th2 cytokine IL-13 plays a key role in allergy, by regulating IgE, airway
      hyper secretion, eosinophils and mast cells. In this study, we aimed to identify
      novel transcription factors (TFs) that potentially regulated IL-13. We analyzed
      Th2 polarized naive T cells from four different blood donors with gene expression
      microarrays to find clusters of genes that were correlated or anti-correlated
      with IL13. These clusters were further filtered, by selecting genes that were
      functionally related. In these clusters, we identified three transcription
      factors (TFs) that were predicted to regulate the expression of IL13, namely
      CEBPB, E2F6 and AHR. siRNA mediated knockdowns of these TFs in naive polarized T
      cells showed significant increases of IL13, following knockdown of CEBPB and
      E2F6, but not AHR. This suggested an inhibitory role of CEBPB and E2F6 in the
      regulation of IL13 and allergy. This was supported by analysis of E2F6, but not
      CEBPB, in allergen-challenged CD4+ T cells from six allergic patients and six
      healthy controls, which showed decreased expression of E2F6 in patients. In
      summary, our findings indicate an inhibitory role of E2F6 in the regulation of IL
      13 and allergy. The analytical approach may be generally applicable to elucidate
      the complex regulatory patterns in Th2 cell polarization and allergy.

PMID- 22981206
TI  - [Alcohol withdrawal delirium: a retrospective case series of 39 patients].
AB  - INTRODUCTION: Alcohol withdrawal delirium (AWD) is one of the most serious
      complications of alcohol withdrawal. The daily practice of linking activity in
      addiction shows that this condition is not uncommon. PATIENTS AND METHODS: We
      extracted from the hospital database patients' admissions for which a diagnosis
      of AWD (F104) was registered between 2004 and 2009. The review of discharge
      reports allowed to select the patients for which the medical records were
      analyzed. RESULTS: Thirty-nine patients admitted for DT were selected. Mean age
      was 48 years (male 89.7%). A majority of patients (89.7%) were admitted through
      the emergency department. In about a half of cases (51.3%), blood alcohol
      concentration was null at admission. The main reasons for the admission were
      alcohol withdrawal syndrome (17.9%), fall/malaise (15.4%), and generalized
      seizures (12.8%). Approximately one-third of the patients had a medical history
      of seizures and 23.1% of AWD. No patient had severe liver failure. Six patients
      (15.4%) were transferred to intensive care. Two patients developed AWD after
      surgery. No deaths have been observed. CONCLUSION: Improving medical knowledge of
      AWD is a way to make this complication even more uncommon.

PMID- 22981207
TI  - [HIV and noma in Burkina Faso].
AB  - INTRODUCTION: Noma is a "gangrenous" disease beginning in gums and spreading to
      other parts of the face. It usually occurs in undernourished children with bad
      orodental hygiene. Its incidence in adults is increasing. HIV infection is very
      common in African countries. We had for objective to compare noma characteristics
      in patients with, or without, HIV. MATERIAL AND METHODS: This retrospective and
      descriptive study included patients managed for noma in our unit from January
      1988 to December 2007. The clinical, epidemiological, and outcome data of
      patients treated for noma were compared according to HIV infection status.
      RESULTS: Two hundred and twelve patients were included and 14 (6.6%) among them
      were HIV positive. In the HIV positive group, there were a male predominance and
      patients were older (mean age 15.3 vs. 4.7 years in the other group). HIV
      positive patients were less frequently operated (35.7% vs. 76.3%) and their death
      rate was higher (37.5% vs. 5.6%). DISCUSSION: HIV infection during the course of
      noma impacts the clinical and epidemiological features of this condition. It
      worsens the prognosis. Noma could be considered as an opportunistic infection in
      the WHO disease staging system.

PMID- 22981208
TI  - Retrospective analysis of clinical outcomes with neoadjuvant cisplatin-based
      regimens for muscle-invasive bladder cancer.
AB  - BACKGROUND: The benefit of neoadjuvant methotrexate, vinblastine, doxorubicin
      (Adriamycin), and cisplatin (MVAC) for muscle-invasive bladder cancer (MIBC) has
      been prospectively demonstrated in a phase III study. Extrapolating from
      comparative data in the metastatic setting, platinum doublets such as cisplatin
      gemcitabine (CG) have been adopted. We sought to compare clinical outcomes in
      patients treated for MIBC with neoadjuvant CG and MVAC at our institution.
      PATIENTS AND METHODS: Patients with MIBC were identified from a prospectively
      maintained registry. Clinicopathologic information and clinical outcome data were
      obtained directly from the registry. When available, pharmacy records were
      reviewed to ascertain the use of growth factors and chemotherapy dose intensity
      (DI). Survival was compared in subgroups divided by the regimen of chemotherapy
      rendered (ie, CG vs. MVAC) using the Kaplan-Meier method. RESULTS: Median overall
      survival (OS) in the overall cohort (N = 61) was 23 months. OS was improved in
      patients receiving either MVAC or CG chemotherapy compared with patients
      receiving "other" chemotherapy (35.3 vs. 16.3 months; P = .055). Although the
      median OS associated with neoadjuvant CG numerically exceeded the survival
      associated with neoadjuvant MVAC (104.3 and 21.8 months, respectively), this was
      not statistically significant (P = .73). Pathologic downstaging predicted
      improved OS with both neoadjuvant CG and MVAC, and the rates of downstaging were
      similar with both regimens. CONCLUSIONS: Although warranting prospective
      validation, our data suggest that CG is a possible alternative neoadjuvant
      approach to traditional regimens such as MVAC for patients with MIBC.

PMID- 22981209
TI  - False positive 2-(18)Fluroro-deoxy-D-glucose positron emission tomography (FDG
      PET) in patients with disseminated seminoma and post-chemotherapy residual
      masses.

PMID- 22981210
TI  - Malignant degeneration within a fibroepithelial polyp of the glans penis: a case
      report and literature review.

PMID- 22981211
TI  - Applications of Tandem Mass Spectrometry (LC-MSMS) in estimating the post-mortem
      interval using the biochemistry of the vitreous humour.
AB  - It is widely accepted that the quantification of potassium concentrations ([K+])
      and hypoxanthine ([Hx]) in the vitreous humour is useful in estimating the time
      of death within a recent time interval. Despite all the advances made in this
      area, it is well recognized that difficulties in calibration, validation and the
      use of different methodologies and instrumentation from different laboratories
      may lead to obtaining different concentrations from the same sample. The
      extraction of the vitreous humour itself should also be carried out with a
      precise technique, taking care during the procedure to avoid causing any vascular
      injury that might lead to haematic contamination. Any fluid that is not clear
      could lead to erroneous results and should be discarded. We present a new LC-MSMS
      method developed for quantitative and qualitative analysis of [Hx] (valid also
      for guanine and xanthine), and qualitative determination of uric acid in vitreous
      humour. We also introduce a methodology to assess haematic contamination in order
      to improve the estimation of time since death. The method was fully validated in
      terms of linearity, sensitivity, imprecision, analytical recovery, extraction and
      process efficiency and matrix effect.

PMID- 22981212
TI  - Fatal diving accidents in western Norway 1983-2007.
AB  - Despite efforts to reduce their number, fatal diving accidents still occur. The
      circumstances and post-mortem findings in 40 fatal diving accidents in western
      Norway from 1983 through 2007 were investigated. Diving experience, medical
      history and toxicology reports were retrieved. The material consisted of
      recreational divers, professional saturation divers and professional divers
      without experience with saturation. In 33 cases the diving equipment was examined
      as part of the forensic investigation. In 27 cases defects in the diving
      equipment were found. For six divers such defects were responsible for the fatal
      accidents. Eighteen divers died on the surface or less than 10 m below surface.
      Five divers reached below 100 msw, and two of them died at this depth. The
      fatalities were not season-dependent. However, wave-height and strength of
      currents were influential factors in some cases. Twelve divers were diving alone.
      Twenty divers had one buddy, 9 of these divers were alone at the time of death.
      The cause of death was drowning in 31 out of 40 divers; one of them had a high
      blood-ethanol concentration, in two other divers ethanol was found in the urine,
      indicating previous ethanol consumption. Nine divers died from sudden
      decompression, pulmonary barotraumas, underwater trauma and natural causes. The
      study shows that most of the fatal diving accidents could be avoided if adequate
      diving safety procedures had been followed.

PMID- 22981213
TI  - Cocaine in sudden and unexpected death: a review of 49 post-mortem cases.
AB  - Cocaine is a potent sympathomimetic drug that is associated with cardiotoxicity,
      including ventricular arrhythmia, systemic hypertension, acute myocardial
      infarction and left ventricular hypertrophy. The use of cocaine in Australia has
      risen steadily since the late 1990s. What remains unclear in the literature is
      whether cocaine-associated death can occur in the absence of other contributing
      factors, such as concomitant drug use or natural disease. A search was conducted
      on the National Coroners Information System database, to identify all deaths
      occurring in Victoria, Australia, between January 2000 and December 2011, where
      cocaine or its metabolites were detected by post-mortem toxicological analysis.
      All cases were closed by the Coroner. These cases were examined with regards to
      case circumstances, pathology and toxicology results, and coronial findings, to
      determine the prevalence of cardiotoxicity and the involvement of cocaine in the
      deaths compared with other contributing factors. There were 49 cases where
      cocaine, benzoylecgonine, ecgonine methyl ester, methylecgonine or cocaethylene,
      were detected in the 11-year period. The individuals ranged in age from 16 to 70
      years (median 30). There were 36 males. In 22 cases the cause of death was
      determined to be drug toxicity, 22 were external injury and 5 were attributed to
      natural disease. The concentration of cocaine in the cases was relatively low
      (range 0.01-3 mg/L, median 0.1 mg/L). Cocaine metabolites were detected
      frequently in blood and urine: benzoylecgonine (46 cases); ecgonine methyl ester
      (12 cases); cocaethylene (8 cases); and methylecgonine (9 cases). Opioids were
      commonly detected (23 cases), in addition to amphetamines (15 cases), ethanol (17
      cases) and benzodiazepines (12 cases). Of the 43 cases receiving a full autopsy,
      there were 14 cases involving significant heart disease. This included coronary
      artery disease (11 cases), an enlarged heart (5 cases), myocarditis and
      contraction band necrosis. Cocaine is detected relatively infrequently in
      Victorian coronial cases. However it appears to be associated with a significant
      degree of cardiotoxicity, particularly coronary artery disease and ventricular
      hypertrophy, independent of cocaine concentration.

PMID- 22981214
TI  - Death by starvation. Seeking a forensic psychiatric understanding of a case of
      fatal child maltreatment by the parent.
AB  - In the Western world, cases of fatal child neglect due to starvation are
      extremely rare. When they do occur, particularly at the hands of a parent, such
      crimes are considered to be caused by mental disorders or personality disorders
      with severe affective impairment. The present report describes the peculiar case
      of a couple with a total of four children to care for, who starved a 16-month-old
      female to death, while all the other children were found to be healthy. After a
      forensic psychiatric assessment of their criminal responsibility, the couples
      were both judged guilty and sentenced to 30 years in prison. After a brief
      overview of the scientific knowledge about filicide, the authors propose a
      framework that may help to understand and explain the motivations underlying this
      dreadful crime that shocked the nation, and emphasize the role of the forensic
      psychiatric investigation into cases of filicide, which may contribute to gain a
      greater insight into the different motivational factors underlying this
      phenomenon.

PMID- 22981215
TI  - Risks of non-lethal weapon use: case studies of three French victims of stinger
      grenades.
AB  - The development of non-lethal weapons started in the 1960s. In France, they have
      been used by the police for about 10 years. We relate the cases of three French
      women, victims of stinger grenades, non-lethal weapons recently adopted by the
      French law enforcement to distract and disperse crowds. The three victims
      presented serious injuries requiring emergency surgical care. One lost her eye.
      Based on these cases, we discuss the lethal character of these weapons and
      propose measures to be taken to prevent their dramatic consequences. Although the
      danger is obviously less than for firearms, stinger grenades are nonetheless
      potentially lethal and cause serious physical injuries.

PMID- 22981218
TI  - 90Yttrium PET-CT images assessing radioisotopic knee synoviorthesis.

PMID- 22981217
TI  - Lung ventilation/perfusion scintigraphy in pulmonary capillary hemangiomatosis: a
      pattern to consider.
AB  - Pulmonary capillary hemangiomatosis is a rare disease, characterized by small
      capillaries proliferation, leading to pulmonary hypertension. The authors report
      a case of pulmonary capillary hemangiomatosis, and discuss its diagnostic
      difficulties. Special attention is presented to ventilation/perfusion
      scintigraphy, given both its importance to the evaluation of pulmonary
      hypertension, and its referred limited usefulness in pulmonary capillary
      hemangiomatosis. The few published cases of ventilation/perfusion scintigraphy on
      this entity have showed different patterns, which are discussed. This case
      presents a pattern with augmented perfusion on lung bases and normal ventilation,
      which has been described by other authors as typical for pulmonary capillary
      hemangiomatosis. The authors consider important to retain this pattern, when
      evaluating pulmonary hypertensive patients, given not only its possible ability
      to help on pulmonary capillary hemangiomatosis diagnosis, but also mainly its
      risk of misinterpretation as a decreased perfusion on upper lung lobes, leading
      to erroneous diagnostic hypotheses.

PMID- 22981216
TI  - Pharmacokinetics of the estrogen receptor subtype-selective ligands, PPT and DPN:
      quantification using UPLC-ES/MS/MS.
AB  - Estrogen receptor (ER) subtype specific agonists, diarylpropionitrile (DPN) for
      ERbeta and propylpyrazoletriol (PPT) for ERalpha, are pharmacological probes used
      frequently to define mechanisms for estrogen actions in vitro and in vivo.
      Quantitative analytical methodology was developed and validated for DPN and PPT,
      based on synthetic stable labeled analogs (DPN-d(4) and PPT-d(5)) using isotope
      dilution liquid chromatographic tandem electrospray mass spectrometric detection.
      The validated method produced high sensitivity, with detection limits of 0.04
      0.07ng/ml serum. Serum pharmacokinetics were evaluated in Long-Evans rats
      following a single subcutaneous injection (2mg/kg bw) of both compounds. The role
      of Phase II metabolism was evaluated using beta-glucuronidase and arylsulfatase
      hydrolysis to measure total DPN and PPT in addition to the parent compounds. The
      pharmacokinetic properties of DPN and PPT reported could facilitate experimental
      designs requiring specified levels of receptor occupancy for quantitative
      comparisons of ER subtype specificities for natural and synthetic estrogens in
      vivo.

PMID- 22981219
TI  - Sentinel node identification with a portable gamma camera in a case without
      visualization on conventional lymphoscintigraphy and SPECT/CT.

PMID- 22981220
TI  - Physiological simulation of blood flow in the aorta: comparison of hemodynamic
      indices as predicted by 3-D FSI, 3-D rigid wall and 1-D models.
AB  - Interest in patient-specific blood-flow circulation modeling has increased
      substantially in recent years. The availability of clinical data for geometric
      and elastic properties together with efficient numerical methods has now made
      model rendering feasible. This work uses 3-D fluid-structure interaction (FSI) to
      provide physiological simulation resulting in modeling with a high level of
      detail. Comparisons are made between results using FSI and rigid wall models. The
      relevance of wall compliance in determining parameters of clinical importance,
      such as wall shear stress, is discussed together with the significance of
      differences found in the pressure and flow waveforms when using the 1-D model.
      Patient-specific geometry of the aorta and its branches was based on MRI
      angiography data. The arterial wall was created with a variable thickness. The
      boundary conditions for the fluid domain were pressure waveform at the ascending
      aorta and flow for each outlet. The waveforms were obtained using a 1-D model
      validated by in vivo measurements performed on the same person. In order to mimic
      the mechanical effect of surrounding tissues in the simulation, a stress
      displacement relation was applied to the arterial wall. The temporal variation
      and spatial patterns of wall shear stress are presented in the aortic arch and
      thoracic aorta together with differences using rigid wall and FSI models. A
      comparison of the 3-D simulations to the 1-D model shows good reproduction of the
      pressure and flow waveforms.

PMID- 22981221
TI  - New insights into the understanding of flow dynamics in an in vitro model for
      abdominal aortic aneurysms.
AB  - An in vitro dynamics set-up of the flow in a compliant abdominal aortic aneurysm
      (AAA) model with an anterior posterior asymmetry, aorto-iliac bifurcation, and
      physiological inlet flow rate and outlet pressure waveforms was developed. The
      aims were first to show that the structural mechanical behavior of the used
      material to mimic the AAA wall was similar to this of patients with AAA and then
      to study the influence of the aorto-iliac bifurcation presence and to study the
      influence of the imbalanced flow rate in the iliac branches on the AAA flow
      field. 3D visualizations, never performed in the literature, have clearly put
      into evidence the development of a vortex ring generated at the AAA proximal neck
      during the decelerating phase of flow rate, which detaches and progresses
      downstream during the cardiac cycle, impinges on the anterior wall in the distal
      AAA region, breaks up, and separates into two vortices of which one rolls on
      upstream along the anterior wall. 2D particle image velocimetry measurements,
      swirling strength and enstrophy calculations allowed quantification of the
      vorticity, vortex trajectory and energy for the different geometrical and
      hydrodynamical conditions. The main results show that the instant and the
      intensity of the vortex ring impingement depend on the presence of the aorto
      iliac bifurcation, with higher intensity, by about 90%, for an AAA without
      bifurcation. The imbalance of the flow rates into the iliac branches induces
      different propagation velocities of the vortex ring and lowers the intensity of
      the vortex impact by about 60%. The potential influence of the AAA dynamics is
      discussed in terms of AAA remodeling and rupture.

PMID- 22981222
TI  - Development of pneumococcal mastoiditis due to multidrug-resistant serotype 19A
      despite three doses of 13-valent pneumococcal vaccine.
AB  - Acute mastoiditis is a potential complication of acute otitis media (AOM), with
      Streptococcus pneumoniae historically the most common pathogen isolated.
      Following the release of the 7-valent pneumococcal conjugate vaccine in 2000, a
      marked decline in invasive pneumococcal disease and a smaller reduction in
      pneumococcal AOM were observed, but data regarding its impact on acute
      mastoiditis are limited. With the recent introduction of the 13-valent
      pneumococcal conjugate vaccine (PCV13), it is anticipated that pneumococcal AOM
      and invasive disease will further diminish. We report a case of acute mastoiditis
      from a multidrug-resistant serotype 19A S. pneumoniae in an immunocompetent child
      who had received three PCV13 vaccinations.

PMID- 22981223
TI  - Inhibition of damage-regulated autophagy modulator-1 (DRAM-1) impairs neutrophil
      differentiation of NB4 APL cells.
AB  - The damage-regulator autophagy modulator 1 (DRAM-1) is a lysosomal protein that
      positively regulates autophagy in a p53-dependent manner. We aimed at analyzing
      the role of DRAM-1 in granulocytic differentiation of APL cells. We observed a
      significant increase of DRAM-1 expression during all-trans retinoic acid (ATRA)
      induced neutrophil differentiation of NB4 APL cells but not in ATRA-resistant NB4
      R2 cells. Next, knocking down DRAM-1 in NB4 APL cells was sufficient to impair
      neutrophil differentiation. Given that DRAM-1 is a transcriptional target of p53,
      we tested if DRAM-1 is regulated by the p53 relative p73. Indeed, inhibiting p73
      prevented neutrophil differentiation and DRAM-1 induction of NB4 cells. In
      conclusion, we show for the first time that p73-regulated DRAM-1 is functionally
      involved in neutrophil differentiation of APL cells.

PMID- 22981224
TI  - Intracellular superoxide dismutase activity defines invasiveness of the murine T
      lymphoma cell line L5187Y-ML25 in vitro and in vivo.
AB  - Superoxide anion in the tumor microenvironment promotes a malignant phenotype.
      Here, we examined superoxide in a murine T-lymphoma cell line L5187Y-ML25. Clones
      with high and low intracellular superoxide dismutase (SOD) activities were
      obtained from parental L5187Y-ML25 cells and were subjected to assays determining
      cell invasiveness, motility, and in vivo dissemination. Cells with lower SOD
      activity exhibited higher invasiveness in vitro and in vivo. NADPH oxidase
      inhibitor suppressed intracellular free radical levels and cell motility,
      suggesting NADPH oxidase as a source of superoxides that stimulates cell
      motility. These results implicate superoxide as a potential anti-metastatic
      therapy for hematopoietic cell malignancies.

PMID- 22981226
TI  - Subaortic right ventricular characteristics and relationship to exercise capacity
      in congenitally corrected transposition of the great arteries.
AB  - BACKGROUND: In congenitally corrected transposition of the great arteries (cc
      TGA), the morphologic right ventricle acts as the subaortic (systemic) ventricle,
      and deterioration of the ventricle over time is a well-known complication. The
      objective of this study was to characterize the right ventricle and explore
      factors that may be contributing to ventricular dilation and dysfunction and the
      relationship with exercise capacity. METHODS: This was a prospective study of
      adults with cc-TGA. All patients underwent cardiopulmonary stress testing,
      ventricular volume and fibrosis assessment by cardiac magnetic resonance imaging,
      and Velocity Vector Imaging strain echocardiography. RESULTS: Twenty-six patients
      were included (mean age, 38 +/- 16 years; 54% women). Exercise capacity was
      significantly reduced in patients with cc-TGA compared with normal subjects (20.9
      +/- 6.0 vs 30.8 +/- 9.2 mL/kg/min, P = .001). The majority of patients (61%) had
      right ventricular (RV) ejection fractions <= 40%. There was no evidence of
      fibrosis on cardiac magnetic resonance imaging. There was a significant
      difference in diastolic volumes among those with RV ejection fractions > 40%
      versus <= 40% (173 +/- 29mL vs 233 +/- 65 mL, P = .02) and moderate or severe
      versus no or mild tricuspid regurgitation (240 +/- 80mL vs 190 +/- 38mL, P =
      .04). RV apical longitudinal and mid free wall circumferential strain was
      decreased compared with these values in controls. CONCLUSIONS: In this relatively
      "well" cc-TGA population, subaortic RV dilation, dysfunction, and exercise
      intolerance are a common problem. Significant systemic tricuspid atrioventricular
      valvular regurgitation is an important contributor to the problem. In this study,
      subaortic RV myocardial deformation parameters were found to be abnormal,
      suggesting that there is a failure of the ventricle to adapt to systemic
      pressures, and therapies to reduce afterload should be explored. Recurrent
      ischemia resulting in fibrosis likely does not contribute to RV dilation or
      dysfunction as demonstrated by the magnetic resonance imaging findings in this
      study.

PMID- 22981225
TI  - A temporal chromatin signature in human embryonic stem cells identifies
      regulators of cardiac development.
AB  - Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular
      cells provides a model for studying molecular mechanisms of human cardiovascular
      development. Although it is known that chromatin modification patterns in ESCs
      differ markedly from those in lineage-committed progenitors and differentiated
      cells, the temporal dynamics of chromatin alterations during differentiation
      along a defined lineage have not been studied. We show that differentiation of
      human ESCs into cardiovascular cells is accompanied by programmed temporal
      alterations in chromatin structure that distinguish key regulators of
      cardiovascular development from other genes. We used this temporal chromatin
      signature to identify regulators of cardiac development, including the homeobox
      gene MEIS2. Using the zebrafish model, we demonstrate that MEIS2 is critical for
      proper heart tube formation and subsequent cardiac looping. Temporal chromatin
      signatures should be broadly applicable to other models of stem cell
      differentiation to identify regulators and provide key insights into major
      developmental decisions.

PMID- 22981227
TI  - Echocardiographic measures of myocardial deformation by speckle-tracking
      technologies: the need for standardization?
AB  - BACKGROUND: Multiple vendor-specific two-dimensional speckle-tracking
      echocardiographic algorithms with which to characterize myocardial mechanics are
      commercially available. The purpose of this study was to compare global
      longitudinal strain (GLS) results between two independent software vendors using
      a neutral image platform. METHODS: A convenience sample of 100 prospectively
      collected patients was evaluated. Subjects with more than two left ventricular
      endocardial segments poorly delineated were excluded. GLS was obtained from the
      apical four-chamber, three-chamber, and two-chamber views using two independent
      speckle-tracking echocardiographic software packages (EchoInsight version 1.5.0
      and Image-Arena version 4.5). Linear regression analysis and paired t tests were
      used to compare GLS results. Intraclass correlation coefficients and Bland-Altman
      plots were used for assessments of reliability. RESULTS: The "out-of-the-box"
      mean GLS was -12.99 +/- 2.38% using EchoInsight and -16.87 +/- 2.84% using Image
      Arena (mean difference, 3.87 +/- 2.42%; P = .0001). Agreement between the
      software packages was moderate (intraclass correlation coefficient, 0.43; 95%
      confidence interval, 0.32-0.55). Using uniform variables to derive GLS
      (Lagrangian strain measured in systole and diastole at the endocardium and
      averaging the peak segmental strain curves), EchoInsight GLS was -16.17 +/- 2.90%
      and Image-Arena GLS was -16.87 +/- 2.84% (mean difference, 0.70 +/- 2.75%; P =
      .02), with an intraclass correlation coefficient of 0.70 (95% confidence
      interval, 0.52-0.79). CONCLUSIONS: Image-Arena GLS results were consistently
      different (more negative) than EchoInsight measures out of the box but became
      similar when information used to derive GLS was uniform. The evolution of
      measures of myocardial mechanics into routine clinical practice will require
      vigilance and standardization of the various techniques, necessitating
      independent validation of commercially available speckle-tracking
      echocardiographic products.

PMID- 22981228
TI  - Variability of global left ventricular deformation analysis using vendor
      dependent and independent two-dimensional speckle-tracking software in adults.
AB  - BACKGROUND: Evaluation of myocardial deformation by two-dimensional speckle
      tracking is useful for clinical and research purposes. However, differences may
      exist among different ultrasound machines, software packages, frame rates, and
      observers. METHODS: Thirty patients underwent echocardiography on both GE (Vivid
      9; GE Vingmed Ultrasound AS, Horten, Norway) and Philips (iE33; Philips
      Ultrasound, Bothell, WA) ultrasound systems. From each study, two sets of images
      were stored in Digital Imaging and Communications in Medicine format, optimized
      for strain evaluation: one set of images at the acquisition frame rate (55-90
      frames/sec) and one set of images at a compressed frame rate of 30 frames/sec.
      Vendor-independent software (VIS; TomTec 2D Cardiac Performance Analysis, Munich,
      Germany) was used to measure strain in multiple directions and was compared with
      vendor-specific software (GE EchoPAC; GE Vingmed Ultrasound AS). RESULTS:
      Intraobserver and interobserver coefficients of variation ranged from 5.5% to
      8.7% for longitudinal strain, from 10.7% to 20.8% for circumferential, and from
      15.3% to 33.4% for radial and transverse strain. Strain values obtained using VIS
      were comparable with those obtained using vendor-specific software for
      longitudinal strain, regardless of ultrasound machine or frame rate. For
      circumferential strain, a consistent large bias was observed between VIS and
      vendor-specific software, with higher values using VIS. Slightly higher strain
      values were observed by analysis at the acquisition frame rate compared with the
      low frame rate, but no consistent bias was observed between images from different
      vendors. CONCLUSIONS: Global longitudinal strain consistently showed good
      reproducibility, while reproducibility was moderate for circumferential strain
      and poor in the radial direction. Retrospective analysis of legacy Digital
      Imaging and Communications in Medicine data at 30 frames/sec can be reliably
      performed for longitudinal strain.

PMID- 22981229
TI  - County-level determinants of dental utilization for Medicaid-enrolled children
      with chronic conditions: how does place affect use?
AB  - Little is known about how place affects childrens' access to dental care. We
      analyzed data for 25,908 Iowa Medicaid-enrolled children with chronic conditions
      to identify the county-level determinants of dental utilization. Our analyses
      suggest that higher levels of poverty and designation as a dental health
      professional shortage area at the county-level are associated with lower
      probability of child-level dental use. There are significant interactions between
      child-level race/ethnicity and county-level poverty as well as between child
      level disability and county-level unemployment. We present a new descriptive
      model on dental utilization that emphasizes county-level factors as well as
      interactions between county-level and child-level factors.

PMID- 22981230
TI  - Barrett's metaplasia as a paradigm for understanding the development of cancer.
AB  - The conversion of one cell type to another is defined as metaplasia (or sometimes
      it is referred to as transdifferentiation or cellular reprogramming). Metaplasia
      is important clinically and may predispose to the development of cancer.
      Barrett's metaplasia is one such example and is the focus of the present review.
      Barrett's is a pathological condition in which the normal oesophageal stratified
      squamous epithelium is replaced by intestinal-type columnar epithelium and is
      associated with gastro-oesophageal reflux disease. The appearance of columnar
      epithelium in the oesophagus predisposes to the development of adenocarcinoma.
      Herein we review the latest evidence on the cellular origin of Barrett's
      metaplasia. Until recently it was thought that the cellular origin of the
      columnar epithelium was from a pre-existing cell within the oesophagus. However,
      recent evidence suggests that this may not be the case. Instead two recent
      publications indicate that the columnar cells may migrate from a site distal to
      the oesophagus. These new data contravene our current understanding of metaplasia
      and raise important questions about the cellular origin of cancer.

PMID- 22981231
TI  - Anticancer activity of the cholesterol exporter ABCA1 gene.
AB  - The ABCA1 protein mediates the transfer of cellular cholesterol across the plasma
      membrane to apolipoprotein A-I. Loss-of-function mutations in the ABCA1 gene
      induce Tangier disease and familial hypoalphalipoproteinemia, both cardiovascular
      conditions characterized by abnormally low levels of serum cholesterol, increased
      cholesterol in macrophages, and subsequent formation of vascular plaque.
      Increased intracellular cholesterol levels are also frequently found in cancer
      cells. Here, we demonstrate anticancer activity of ABCA1 efflux function, which
      is compromised following inhibition of ABCA1 gene expression by oncogenic
      mutations or cancer-specific ABCA1 loss-of-function mutations. In concert with
      elevated cholesterol synthesis found in cancer cells, ABCA1 deficiency allows for
      increased mitochondrial cholesterol, inhibits release of mitochondrial cell death
      promoting molecules, and thus facilitates cancer cell survival, suggesting that
      elevated mitochondrial cholesterol is essential to the cancer phenotype.

PMID- 22981232
TI  - Roles of dom34:hbs1 in nonstop protein clearance from translocators for normal
      organelle protein influx.
AB  - Because messenger RNAs without a stop codon (nonstop mRNAs) generate stalled
      ribosomes, cells have developed a mechanism allowing degradation of nonstop mRNAs
      and their translation products (nonstop proteins) in the cytosol. Here, we
      observe the fate of nonstop proteins destined for organelles such as the
      endoplasmic reticulum (ER) and mitochondria. Nonstop mRNAs for secretory-pathway
      proteins in yeast generate nonstop proteins that become stuck in the
      translocator, the Sec61 complex, in the ER membrane. These stuck nonstop
      secretory proteins avoid proteasomal degradation in the cytosol, but are instead
      released into the ER lumen through stalled ribosome and translocator channels by
      Dom34:Hbs1. We also found that nonstop mitochondrial proteins are cleared from
      the mitochondrial translocator, the TOM40 complex, by Dom34:Hbs1. Clearance of
      stuck nonstop proteins from organellar translocator channels is crucial for
      normal protein influx into organelles and for normal cell growth, especially when
      nonstop mRNA decay does not function efficiently.

PMID- 22981234
TI  - Generation and characterization of severe combined immunodeficiency rats.
AB  - Severe combined immunodeficiency (SCID) mice, the most widely used animal model
      of DNA-PKcs (Prkdc) deficiency, have contributed enormously to our understanding
      of immunodeficiency, lymphocyte development, and DNA-repair mechanisms, and they
      are ideal hosts for allogeneic and xenogeneic tissue transplantation. Here, we
      use zinc-finger nucleases to generate rats that lack either the Prkdc gene (SCID)
      or the Prkdc and Il2rg genes (referred to as F344-scid gamma [FSG] rats). SCID
      rats show several phenotypic differences from SCID mice, including growth
      retardation, premature senescence, and a more severe immunodeficiency without
      "leaky" phenotypes. Double-knockout FSG rats show an even more immunocompromised
      phenotype, such as the abolishment of natural killer cells. Finally,
      xenotransplantation of human induced pluripotent stem cells, ovarian cancer
      cells, and hepatocytes shows that SCID and FSG rats can act as hosts for
      xenogeneic tissue grafts and stem cell transplantation and may be useful for
      preclinical testing of new drugs.

PMID- 22981235
TI  - Cell competition time line: winners kill losers, which are extruded and engulfed
      by hemocytes.
AB  - Cell competition is a mechanism that eliminates slow dividing cells from a
      growing population. It is believed that the genes wasp, psr, and draper are
      active in the cells that win the competition ("winner cells") and that they are
      essential in the winner cells for the induction of apoptosis and for the
      elimination of the "loser cells." Here, we show that lack of those genes in
      winner cells appears to be dispensable for cell-competition-induced apoptosis and
      during dmyc-induced supercompetition. Moreover, winner clones do not need those
      genes in order to preserve their growth advantage. Finally, we find that most of
      the clearance of the apoptotic debris is not performed by winners but by
      recruited hemocytes, which are required for the removal of the apoptotic corpses
      at the very end. Therefore, engulfment is a consequence-not a cause-of loser
      cells' death.

PMID- 22981233
TI  - Identification of the hemogenic endothelial progenitor and its direct precursor
      in human pluripotent stem cell differentiation cultures.
AB  - Hemogenic endothelium (HE) has been recognized as a source of hematopoietic stem
      cells (HSCs) in the embryo. Access to human HE progenitors (HEPs) is essential
      for enabling the investigation of the molecular determinants of HSC
      specification. Here, we show that HEPs capable of generating definitive
      hematopoietic cells can be obtained from human pluripotent stem cells (hPSCs) and
      identified precisely by a VE-cadherin(+)CD73(-)CD235a/CD43(-) phenotype. This
      phenotype discriminates true HEPs from VE-cadherin(+)CD73(+) non-HEPs and VE
      cadherin(+)CD235a(+)CD41a(-) early hematopoietic cells with endothelial and FGF2
      dependent hematopoietic colony-forming potential. We found that HEPs arise at the
      post-primitive-streak stage of differentiation directly from VE-cadherin-negative
      KDR(bright)APLNR(+)PDGFRalpha(low/-) hematovascular mesodermal precursors
      (HVMPs). In contrast, hemangioblasts, which are capable of forming endothelium
      and primitive blood cells, originate from more immature APLNR(+)PDGFRalpha(+)
      mesoderm. The demarcation of HEPs and HVMPs provides a platform for modeling
      blood development from endothelium with a goal of facilitating the generation of
      HSCs from hPSCs.

PMID- 22981236
TI  - Psychological, physical, social, and spiritual well-being similarities between
      Korean older adults and family caregivers.
AB  - There is a growing recognition that the similarities between older adults and
      family caregivers has both practical and research implications; caregivers' well
      being influences older adults' well-being and vice versa. There has been a
      paucity of studies that explore the similarities between Korean older adults and
      their caregivers. This study aims to examine psychological, physical, social, and
      spiritual well-being similarities among 157 older adult-caregiver dyads in Seoul,
      Korea. There was a significant degree of similarities between older adults and
      their caregivers with respect to psychological, social, and spiritual well-being,
      but not to physical well-being. Present findings suggest that nurses and other
      health care professionals should be involved and collaborate with family
      caregivers to take care of older adults; to understand the dynamic, caring
      relationships between older adults and their family caregivers; and to improve
      the well-being of older adults as well as their family caregivers.

PMID- 22981238
TI  - Possibly lifesaving, noninvasive, EEG-guided neuromodulation in anesthesia
      refractory partial status epilepticus.
AB  - This study aimed to investigate the effect of low frequency repetitive
      transcranial magnetic stimulation (rTMS) guided as to localization and effect by
      continuous EEG on a super-refractory status epilepticus unresponsive to
      conventional treatment for 44 days including repeated deep sedation. Repetitive
      transcranial magnetic stimulation was delivered for one-hour sessions to the most
      active of two EEG foci for 8 days. From the third day of stimulation, the EEG
      pathology markedly decreased in parallel to clinical improvement. The patient
      could be weaned off the respirator, transferred to an ordinary ward then to a
      rehabilitation clinic. This is the first report of a positive outcome of rTMS
      treatment in super-refractory status epilepticus. In the context of refractory
      partial status epilepticus, neuromodulation through rTMS is a safe treatment
      option. If performed along the lines herein described, it may also be more
      efficient than conventional treatment. Repetitive transcranial magnetic
      stimulation may be an underused treatment option for status epilepticus.

PMID- 22981237
TI  - Low-grade osteomyelitis of the fifth metatarsal with possible concomitant
      Freiberg's disease of the metatarsal head.
AB  - Freiberg's disease, metatarsal avascular necrosis, is most often seen in healthy
      athletic adolescent girls. Presenting symptoms include vague pain, swelling, and
      loss of motion in the involved metatarsophalangeal joints. Low-grade
      osteomyelitis often is difficult to identify. In this case report, we present a
      14-year-old girl with low-grade osteomyelitis of the fifth metatarsal accompanied
      by possible Freiberg's disease in the same metatarsal.

PMID- 22981239
TI  - The Du Bois key.

PMID- 22981240
TI  - Body composition changes after weight-loss interventions for overweight and
      obesity.
AB  - BACKGROUND & AIMS: Weight-loss interventions to correct overweight and obesity
      are very popular but often inappropriate and unsuccessful. METHODS: In this
      review we evaluated studies on body composition changes during and after
      different medical and surgical interventions aimed at achieving stable weight
      loss in overweight and obese individuals. RESULTS: Most of the available
      literature and good clinical practice observations deal mainly with post
      menopausal overweight and obese women, and, to a lesser extent adolescents and
      elderly, female and male, populations. These studies suggest that weight-loss
      maintenance interventions should have greater consideration and priority than
      simple weight-loss treatments. At a long term follow up (over one year),
      relatively high protein, moderately low calorie, low glycemic index diets,
      associated with a daily, moderate intensity, physical exercise (of at least 30
      min), appear to be more successful in limiting long term relapse, maintaining fat
      free mass and achieving the highest fat loss. Diet alone or physical exercise
      alone does not produce similar results. Health professional training and practice
      also appear a challenging target. CONCLUSIONS: Adequate dietetic advice plus
      regular physical exercise avoid the fat-free-mass loss usually observed in the
      relapse of the weight cycling syndrome and prevent the onset of sarcopenic
      obesity.

PMID- 22981241
TI  - The efficacy of zinc supplementation in young children with acute lower
      respiratory infections: a randomized double-blind controlled trial.
AB  - BACKGROUND & AIM: Acute lower respiratory infections are the most frequent
      illnesses globally in children less than 5 years old. The aim of this randomized
      double blind controlled trial is to assess the effectiveness of zinc gluconate
      supplementation for 2 months period compared to placebo in reducing respiratory
      morbidity in acute lower respiratory infected children up to 5 years of age
      living in zinc poor population. METHODS: Children were randomly assigned to
      receive either 10 mg zinc gluconate or placebo for 60 days. Demographic and
      clinical data were collected at baseline and every two weeks for 180 days.
      RESULTS: The final analysis included 96 children allocated equally to the two
      groups. The number of episodes of acute lower respiratory infections and severe
      acute lower respiratory infections were significantly lower in zinc group
      compared to placebo group (20.8% vs. 45.8% (P = 0.009) and 21.7% vs. 58.3% (P <
      0.001), respectively). The acute lower respiratory infections free days were
      higher in the zinc supplemented group (P < 0.001). The median recovery time of
      morbidity was significantly shorter in zinc group (P < 0.001). CONCLUSIONS: Zinc
      supplement may result in significant reduction in respiratory morbidity among
      children with acute lower respiratory infections in zinc poor population. This
      study was registered under ClinicalTrials.gov Identifier no. NCT00536133.

PMID- 22981243
TI  - Integration of retroviral vectors.
AB  - Retroviral vectors are unique in their ability to integrate their genome into the
      host genome of transduced cells. Several members of the retrovirus family show
      distinct pattern for preferential integration into the host genome. Despite many
      years of investigation, precise mechanisms of target site selection and the
      fundamental interplay of viral integrase and host cell proteins are still
      unknown. Improved methods to detect retroviral integrations genome-wide as well
      as recent advances on the retroviral integrase structure and integrase
      interacting proteins may lead to further uncover the process of retroviral target
      site selection. A better knowledge of these mechanisms and interactions will
      allow further improving safety of retroviral vectors for gene therapy by
      providing an opportunity to retarget retroviral integration into non-harmful
      genomic positions.

PMID- 22981242
TI  - Wavelet-transformed temporal cerebral blood flow signals during attempted
      inhibition of cue-induced cocaine craving distinguish prognostic phenotypes.
AB  - BACKGROUND: Cocaine addicted patients with positive cocaine urine status at
      treatment entry are far less likely to have a successful treatment outcome. This
      work aims to identify brain substrates that can distinguish this group of
      patients from their cocaine-negative counterparts in order to better understand
      this clinical phenotype. Going a step beyond conventional functional
      connectivity, we used wavelet transform coherence (WTC) to determine in which
      ways the temporal pattern of fMRI cerebral blood flow (CBF) signals during
      attempted inhibition of cue-induced cocaine craving may differ between these two
      groups. METHODS: Using a critical node in motivational circuitry, amygdala, as a
      seed, whole brain correlations for the entire sample revealed a functional
      connection with the dorsal cingulate. Next, WTC maps of CBF were constructed for
      each individual, characterizing the temporal patterns between these two regions
      during craving inhibition. RESULTS: As revealed by WTC, during attempted craving
      inhibition, the cocaine-negative subjects had significantly stronger and longer
      negative coherence between the amygdala and the dorsal cingulate, as compared to
      the cocaine-positive subjects. This relationship was neither evident in the
      resting state nor between two regions unrelated to inhibition processes.
      CONCLUSIONS: The duration and strength of negative coherence calculated from
      wavelet-transformed CBF provide an objective and well-defined way to characterize
      brain responses during attempted inhibition of cue-induced craving, at the level
      of the individual. The stronger and sustained negative coherence in CBF between
      motivational (amygdala) and modulatory (dorsal cingulate) regions in cocaine
      negative subjects may be a critical brain strength that fosters improved craving
      inhibition and thus, better clinical outcome.

PMID- 22981244
TI  - Comment to 'Nutritional therapy versus 6-mercaptopurine as maintenance therapy in
      patients with Crohn's disease'.

PMID- 22981245
TI  - A complex evaluation of the asymmetry of dermatoglyphs.
AB  - Altogether 20 traits of the fingers, 22 traits of the palm and 8 traits of the
      sole were taken into consideration, on both sides of the bodies of 1652 males and
      1628 females. Numbers of asymmetrical variants of the traits within the whole
      complex of 25 pairs of traits were determined individually. In the case of
      descriptive traits, asymmetry was deemed to be the occurrence on either side of
      the body of non-identical variants of the traits, and for quantitative traits,
      the absolute difference of at least two ridges was accepted. These differences
      were marked with the value 1 (additionally 0.5 on the fingers when the difference
      concerned only the direction of the pattern). The sum of these values constituted
      the total number of asymmetric traits, which was expressed by the index:
      IA=number of asymmetric traits*100/25. For individual traits, the frequency of
      asymmetric variants was determined, and here the measure of asymmetry was
      expressed as the relations of their sum to the total numbers. In both sexes, the
      lowest level of asymmetry concerns patterns of the II inter-digital area, the
      thenar, the IV, III and I areas of the sole, and fingers 5 and 3, while the
      highest level concerns patterns of finger 2, asymmetry of C-line and A-line
      exits, the ridge count on the fingers and in the inter-digital areas of the palm.
      The greatest dimorphism is demonstrated by the asymmetry of the patterns of the
      II inter-digital area of the palm, finger 4, the IV area of the sole, the thenar,
      finger 1, line B and the ridge count on finger 2. As a consequence, the mean of
      the asymmetry index (IA) in males (46.24) is higher than in females (44.43). The
      proposed index of dermatoglyphic asymmetry (IA) may be used for comparative
      purposes in population, clinical, auxological and genetic research.

PMID- 22981246
TI  - Survey finds that most meta-analysts do not attempt to collect individual patient
      data.
AB  - OBJECTIVE: To characterize current efforts and outcomes of individual patient
      data (IPD) collection among meta-analysts of randomized controlled clinical
      trials. STUDY DESIGN AND SETTING: Corresponding authors of meta-analyses of
      randomized controlled trials in general medicine with a binary endpoint were sent
      an e-mail survey inquiring about their efforts to obtain IPD. Descriptive
      statistics of each meta-analysis were extracted to evaluate their association
      with data seeking. RESULTS: Only 22 (4.2%) of the sampled meta-analyses included
      IPD. Of the 360 authors surveyed, 256 (71%) reported not seeking IPD: 48% thought
      that the undertaking would be too difficult, 30% thought that it was not
      necessary for their main analysis, 25% did not have sufficient time or resources,
      and 22% never considered it. Seeking IPD was not significantly associated with
      any trial characteristic examined, including whether subgroup analyses were
      performed. Authors who sought IPD obtained a median of two data sets
      (interquartile range=0-5). Unsuccessful contact (43%), refusal without
      explanation (21%), and lost or inaccessible data (20%) were the most common
      reasons why trial data could not be obtained. CONCLUSION: The infrequency of
      attempts made by meta-analysts to obtain participant data is an important
      contributor to the rarity of IPD meta-analyses.

PMID- 22981247
TI  - The withholding of test results as a means of assessing the effectiveness of
      treatment in test-positive persons.
AB  - In recent years, a number of studies have achieved randomization of patients to
      alternative management strategies by blinding some patients (and their providers
      of medical care) to the results of tests that guide such strategies. Although
      this research approach has the potential to be a powerful means of measuring
      treatment effectiveness, the interpretation of the results may not be
      straightforward if the treatment received by test-positive persons is variable or
      not well documented, or if the analysis is not restricted to outcomes in test
      positive persons. Studies in which the test results are withheld at random may
      face ethical issues that, to date, have received little discussion.

PMID- 22981248
TI  - Experience with GRADE.

PMID- 22981249
TI  - Testing the risk of bias tool showed low reliability between individual reviewers
      and across consensus assessments of reviewer pairs.
AB  - OBJECTIVES: To assess the reliability of the Cochrane Risk of Bias (ROB) tool
      between individual raters and across consensus agreements of pairs of reviewers
      and examine the impact of study-level factors on reliability. STUDY DESIGN AND
      SETTING: Two reviewers assessed risk of bias for 154 randomized controlled trials
      (RCTs). For 30 RCTs, two reviewers from each of four centers assessed risk of
      bias and reached consensus. We assessed interrater agreement using kappas and the
      impact of study-level factors through subgroup analyses. RESULTS: Reliability
      between two reviewers was fair for most domains (kappa=0.24-0.37), except
      sequence generation (kappa=0.79, substantial). Reliability results across
      reviewer pairs: sequence generation, moderate (kappa=0.60); allocation
      concealment and "other sources of bias," fair (kappa=0.37-0.27); and other
      domains, slight (kappa=0.05-0.09). Reliability was influenced by the nature of
      the outcome, nature of the intervention, study design, trial hypothesis, and
      funding source. Variability resulted from different interpretation of the tool
      rather than different information identified in the study reports. CONCLUSION:
      Low agreement has implications for interpreting systematic reviews. These
      findings suggest the need for detailed guidance in assessing the risk of bias.

PMID- 22981250
TI  - Calculating additive treatment effects from multiple randomized trials provides
      useful estimates of combination therapies.
AB  - OBJECTIVE: Many clinicians and decision makers want to know the combined effects
      of treatments that have not been evaluated in combination. It is possible to
      determine such treatment effects by making assumptions about the additive
      effects. We discuss here the prerequisites and methods of applying additivity
      assumptions in synthesizing the evidence from randomized trials and multiple
      treatment meta-analyses. STUDY DESIGN AND SETTING: Using statistical approaches,
      we demonstrate the utility of additivity of both pairwise randomized trials and
      multiple treatment comparison meta-analyses. RESULTS: We present illustratively
      an example on estimating the treatment effects of drug combinations for chronic
      obstructive pulmonary disease. We confirm the additive treatment effects by
      comparing with direct combination treatment trial results. CONCLUSION: Additive
      effects may be a useful tool to estimate the effectiveness of treatment
      combinations.

PMID- 22981251
TI  - Some but not all dyadic measures in shared decision making research have
      satisfactory psychometric properties.
AB  - OBJECTIVE: To assess the psychometric properties of dyadic measures for shared
      decision making (SDM) research. STUDY DESIGN AND SETTING: We conducted an
      observational cross-sectional study in 17 primary care clinics with physician
      patient dyads. We used seven subscales to measure six elements of SDM: (1)
      defining the problem, presenting options, and discussing pros and cons; (2)
      clarifying the patient's values and preferences; (3) discussing the patient's
      self-efficacy; (4) drawing on the doctor's knowledge; (5) verifying the patient's
      understanding; and (6) assessing the patient's uncertainty. We assessed the
      reliability and invariance of the factorial structure and considered a measure to
      be dyadic if the factorial structure of the patient version was similar to that
      of the physician version and if there was equality of loading (no significant chi
      square). RESULTS: We analyzed data for 264 physicians and 269 patients. All
      measures except one showed adequate reliability (Cronbach alpha, 0.70-0.93) and
      factorial validity (root mean square error of approximation, 0.000-0.06).
      However, we found only four measures to be dyadic (P>0.05): the values
      clarification subscale, perceived behavioral subscale, information-verifying
      subscale, and uncertainty subscale. CONCLUSION: The subscales for values
      clarification, perceived behavioral control, information verifying, and
      uncertainty are appropriate dyadic measures for SDM research and can be used to
      derive dyadic indices.

PMID- 22981252
TI  - Active case finding for pulmonary tuberculosis using mobile digital chest
      radiography: an observational study.
AB  - BACKGROUND: Mobile digital chest radiography (CXR) is used routinely to screen
      for pulmonary tuberculosis (PTB) in London among homeless populations, persons
      accessing drug treatment services and prisoners. OBJECTIVE: 1) To establish the
      sensitivity and specificity of mobile digital  CXR, and 2) to test the hypothesis
      that actively identified cases have reduced odds of sputum smear positivity vs.
      those presenting passively to health care services from the same populations.
      METHODS: Sensitivity and specificity were calculated using a gold standard
      comparator of culture-confirmed  cases of PTB reported to the national
      surveillance system within 90 days of screening. Logistic regression was used to
      determine whether actively detected cases had reduced odds of smear positivity
      compared to passively detected cases after adjustment for confounding. RESULTS:
      The intervention  had a sensitivity of 81.8% (95%CI 64.5-93.0) and a specificity
      of 99.2% (95%CI 99.1-99.3). After adjusting for confounding, there was evidence
      that cases identified through screening were less likely to be smear-positive
      than passively identified cases (OR 0.34, 95%CI 0.14-0.85;  likelihood ratio test
      P = 0.022). CONCLUSION: Digital CXR achieves a high level of sensitivity and
      specificity in an operational setting; targeted mobile radiographic screening can
      reduce the risk of onward transmission by identifying cases before they become
      infectious.

PMID- 22981253
TI  - Mild residual pulmonary stenosis in tetralogy of fallot reduces risk of pulmonary
      valve replacement.
AB  - BACKGROUND: Current surgical strategies that aim at preventing pulmonary
      regurgitation in patients with corrected tetralogy of Fallot (cToF) may result in
      a certain grade of residual pulmonary stenosis (PS). The clinical implications of
      a postoperative residual PS in cToF patients remain unclear. Pulmonary valve
      replacement (PVR) is frequently needed during follow-up of cToF patients. The aim
      of the current study was to determine the role of residual PS in the need for PVR
      during follow-up in cToF patients. METHODS: cToF patients were included if
      clinical follow-up after primary surgical correction had taken place for a
      minimum of 5 years. Patient characteristics, surgical factors, and postoperative
      factors were reviewed, with a special focus on the transpulmonic systolic
      gradient. Cox proportional hazards regression analysis was performed to identify
      predictors of PVR. RESULTS: Of 171 cToF patients, 71 (41.5%) underwent PVR after
      24.2 years (interquartile range, 16.8-31.6 years). Year of birth, older age at
      corrective operation, and patch use significantly predicted PVR during follow-up.
      By contrast, a mild residual PS in cToF patients (peak systolic gradient, 15-30
      mm Hg) independently reduced the risk of PVR, as compared with patients without
      PS (hazard ratio, 0.47; p=0.02) and with moderate-to-severe PS (hazard ratio,
      0.35; p=0.01). CONCLUSIONS: In addition to the known risks factors for PVR, a
      postoperative mild residual PS reduces the risk of PVR during follow-up of cToF
      patients. This finding provides clinical evidence for a conservative PS relief
      during correction of ToF.

PMID- 22981254
TI  - Bronchial carcinoid tumors causing Cushing's syndrome: more aggressive behavior
      and the need for early diagnosis.
AB  - BACKGROUND: The aim of this study was to revisit the characteristics and outcomes
      of adrenocorticotropin-secreting bronchial carcinoid tumor (BCT) responsible for
      Cushing's syndrome (CS). METHODS: We conducted a single-institution retrospective
      review of 14 patients who underwent pulmonary resection for BCT that presented as
      CS from October 1993 to November 2011. RESULTS: The group consisted of 8 male
      patients (57%) and 6 female patients. The mean age was 40 years (range, 16-63
      years). Three patients (21%) underwent unnecessary adrenalectomy or
      hypophysectomy, or both, before diagnosis of the main cause. The mean interval
      between clinical presentation and the chest operation was 33 months (range, 3-136
      months). Operations included 12 lobectomies (86%), 1 segmentectomy, and 1 wedge
      excision. All patients underwent radical lymph node dissection. Histologic
      examination showed 11 typical carcinoids (79%) and 3 atypical carcinoids. Twelve
      patients were classified pT1 (86%) and 2 patients were classified pT3 because of
      the presence of 2 tumors in the same lobe. Lymph node metastases were found in 7
      patients (50%) (3 pN1 and 4 pN2). The mean follow-up was 59 months (range, 3-174
      months). No recurrence was observed. CONCLUSIONS: Early detection of
      adrenocorticotropin-secreting BCTs is challenging. However, it avoids
      adrenalectomy and unnecessary hypophysectomy, limits the deleterious effects of
      chronic hypercortisolism, and reduces the risk of metastasis. The high prevalence
      of lymph node involvement confirms the aggressiveness of these tumors and
      justifies anatomic resection and radical lymph node dissection. Under these
      circumstances, the prognosis remains favorable, even in cases of N2 disease.

PMID- 22981255
TI  - Material properties of CorCap passive cardiac support device.
AB  - BACKGROUND: Myocardial function deteriorates during ventricular remodeling in
      patients with congestive heart failure (HF). Ventricular restraint therapy using
      a cardiac support device (CSD) is designed to reduce the amount of stress inside
      the dilated ventricles, which in turn halts remodeling. However, as an open mesh
      surrounding the heart, it is unknown what the mechanical properties of the CSD
      are in different fiber orientations. METHODS: Composite specimens of CorCap
      (Acorn Cardiovascular, Inc, St. Paul, MN) CSD fabric and silicone were
      constructed in different fiber orientations and tested on a custom-built biaxial
      stretcher. Silicone controls were made and stretched to detect the parameters of
      the matrix. CSD coefficients were calculated using the composite and silicone
      matrix stress-strain data. Stiffness in different fiber orientations was
      determined. RESULTS: Silicone specimens exerted a linear behavior, with stiffness
      of 2.57 MPa. For the composites with 1 fiber set aligned with respect to the
      stretch axes, stiffness in the direction of the aligned fiber set was higher than
      that in the cross-fiber direction (14.39 MPa versus 5.66 MPa), indicating greater
      compliance in the cross-fiber direction. When the orientation of the fiber sets
      in the composite were matched to the expected clinical orientation of the
      implanted CorCap, the stiffness in the circumferential axis (with respect to the
      heart) was greater than in the longitudinal axis (10.55 MPa versus 9.70 MPa).
      CONCLUSIONS: The mechanical properties of the CorCap demonstrate directionality
      with greater stiffness circumferentially than longitudinally. Implantation of the
      CorCap clinically should take into account the directionality of the biomechanics
      to optimize ventricular restraint.

PMID- 22981256
TI  - Computational analysis of hybrid Norwood circulation with distal aortic arch
      obstruction and reverse Blalock-Taussig shunt.
AB  - BACKGROUND: The hemodynamics characteristics of the hybrid Norwood (HN) procedure
      differ from those of the conventional Norwood and are not fully understood. We
      present a multiscale model of HN circulation to understand local hemodynamics and
      effects of aortic arch stenosis and a reverse Blalock-Taussig shunt (RBTS) on
      coronary and carotid perfusion. METHODS: Four 3-dimensional models of four HN
      anatomic variants were developed, with and without 90% distal preductal arch
      stenosis and with and without a 4-mm RBTS. A lumped parameter model of the
      circulation was coupled to a local 3-dimensional computational fluid dynamics
      model. Outputs from the lumped parameter model provided waveform boundary
      conditions for the computational fluid dynamics model. RESULTS: A 90% distal arch
      stenosis reduced pressure and net flow-rate through the coronary and carotid
      arteries by 30%. Addition of the RBTS completely restored pressure and flow rate
      to baseline in these vessels. Zones of flow stagnation, flow reversal, and
      recirculation in the presence of stenosis were rendered more orderly by addition
      of the RBTS. In the absence of stenosis, presence of the shunt resulted in
      extensive zones of disturbed flow within the RBTS and arch. CONCLUSIONS: We found
      that a 4-mm * 21-mm RBTS completely compensated for the effects of a 90% discrete
      stenosis of the distal aortic arch in the HN. Placed preventatively, the RBTS and
      arch displayed zones with thrombogenic potential showing recirculation and
      stagnation that persist for a substantial fraction of the cardiac cycle,
      indicating that anticoagulation should be considered with a prophylactic RBTS.

PMID- 22981257
TI  - Arterial switch operation: early and late outcome for intramural coronary
      arteries.
AB  - BACKGROUND: Intramural coronary artery course (IMCA) is associated with an
      increased risk of coronary event and mortality after the arterial switch
      operation (ASO). We describe early and late outcomes at our institution from 1996
      to 2006. METHODS: Operation notes for all patients who underwent ASO within 60
      days of birth were reviewed, and those with IMCA were identified. Mortality and
      morbidity were obtained from discharge summary, predischarge electrocardiogram,
      and echocardiogram. Follow-up included clinical review, electrocardiogram,
      echocardiography, dobutamine stress echocardiography, and angiography. RESULTS:
      Eighteen patients of 215 in the cohort (8.4%) had IMCA. Intramural coronary
      artery course was more common in patients from French Polynesia (6 of 17; 35.3%
      versus 12 of 198; 6.1%; p=0.001). Early mortality for patients with IMCA was 1 of
      18 (5.6%) compared with 6 of 197 (3%) for those without IMCA (p=0.46). One IMCA
      patient was lost to follow-up. The remaining 16 are alive and asymptomatic. Of
      the 13 who underwent angiography, 2 had minor coronary artery stenoses at initial
      nonselective aortic root angiography. Both stenoses resolved at subsequent
      selective coronary angiography. None of the 11 who underwent dobutamine stress
      echocardiography had inducible ischemia. CONCLUSIONS: We report a high prevalence
      of IMCA in an ASO population, particularly among patients referred from French
      Polynesia. Intramural coronary artery course was not a risk factor for mortality
      after ASO. Angiography demonstrated excellent short-term and long-term structural
      outcome for IMCA.

PMID- 22981258
TI  - The conditional role of inflammation in pregnancy and cancer.
AB  - Cancer growth is characterized by proliferation of tumor cells in conjunction
      with invasion of all different immune cells that also invade healing wounds. This
      inflammatory response is necessary for cell proliferation but a second purpose of
      the inflammatory process is so that a low Th1/Th2 ratio is present with
      overexpression of IL-10, TGF-beta and IFN-gamma. Down regulation of NO activity
      also shifts the balance between M1 and M2 macrophages. Both aspects allow the
      antigenous nature of the tumor to escape anti-tumor effects of the host. Support
      for this view comes from observations in pregnancy in which the placenta exhibits
      identical immune responses and downregulation of NO production to allow
      trophoblast cells to invade the uterine tissues without being rejected. Cell
      proliferation requires a metabolic set-up in which the organism produces adequate
      substrate for growth. This also bears the characteristics of a systemic
      inflammatory response delivering a similar substrate mix required for cancer and
      fetal growth. This arrangement is clearly beneficial in pregnancy and therefore
      supports the view that cancer growth is facilitated by the organism: the
      cancerous tumor elicits an immunological response opposing anti-tumor effects and
      induces the host to produce building blocks for growth.

PMID- 22981259
TI  - Clinical spectrum of the pseudotumor cerebri in children: etiological, clinical
      features, treatment and prognosis.
AB  - OBJECTIVE: Pseudotumor cerebri (PTC) is a clinical condition characterized by
      signs and symptoms of increased intracranial pressure, such as headache and
      papilledema. Our aim was to investigate the etiological and clinical features of
      pseudotumor cerebri (PTC) in children. MATERIALS AND METHOD: We performed a
      comprehensive analysis of epidemiology, diagnostic work-up, therapy, and clinical
      follow-up in 42 consecutive patients. RESULTS: Totally 42 patients diagnosed with
      PTC [27 (64.3%) females and 15 (35.7%) males] were included in the study. The
      average age of the symptoms onset was 10.79+/-3.43 years (range from 12 months to
      17 years). Obesity was found in eleven (26.2%) of them. Two of the patients had
      familial mediterranean fever, two of them had posttraumatic PTC. The following
      diseases were one patient, respectively; mycophenolate mofetil-induced PTC,
      hypervitaminosis A induced PTC, corticosteroid induced withdrawal due to
      nephritic syndrome, use of oral contraceptives, Guillain-Barre syndrome, urinary
      tract infection, varicella-zoster virus infection and dural venous sinus
      thrombosis associated with otitis media. The most common symptom was headache,
      recorded in 76.2% of the patients. All patients were treated medically. Three
      patients in our group also required a ventriculoperitoneal shunt. CONCLUSION:
      Pseudotumor cerebri is an avoidable cause of visual loss, both in adults and
      children. Pre-pubertal obese girls are more common. Medical therapy appeared to
      be successful in treating pediatric PTC in most patients. Nevertheless, despite
      adequate treatment, children can rarely experience loss of visual field and
      acuity; thus, prompt diagnosis and management are important.

PMID- 22981260
TI  - Late-onset Leigh syndrome with myoclonic epilepsy with ragged-red fibers.
AB  - We report the case of a boy with myoclonic epilepsy with ragged-red fibers
      (MERRF) who had astatic seizures since 2 years of age and later developed ataxia,
      absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of
      mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed
      late-onset Leigh syndrome (LS) when he contracted pneumonia at 6 years. He
      developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem,
      basal ganglia, and cerebral cortex. Three similar cases have been reported; two
      carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These
      suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype
      of MERRF in the early stage and late-onset Leigh syndrome in the late course of
      the disease.

PMID- 22981261
TI  - Clinical features and varieties of non-motor fluctuations in Parkinson's disease:
      a Japanese multicenter study.
AB  - OBJECTIVE: This multicenter cross-sectional study aimed to investigate the
      clinical features and varieties of non-motor fluctuation in Parkinson's disease
      (PD). METHODS: To identify motor and non-motor fluctuation, we employed the
      wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared
      the frequency of levodopa-related fluctuation as identified by the WOQ-19 with
      recognition by neurologists. We compared patients with both motor and non-motor
      fluctuations with those who only had motor fluctuations. Non-motor fluctuations
      were separated into psychiatric, autonomic, and sensory categories for further
      analysis. RESULTS: The patients' average age was 70.8 +/- 8.4 years (mean +/- SD)
      and disease duration was 6.6 +/- 5.0 years. The frequency of motor fluctuations
      was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with
      motor fluctuations also had non-motor fluctuations, whereas 93% of patients with
      non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a
      sensitivity of 82% but a specificity of only 40%. The patients with both non
      motor and motor fluctuations exhibited more severe motor symptoms, more non-motor
      symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly
      higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms
      than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of
      patients with non-motor fluctuations exhibited more than one type of non-motor
      fluctuation. CONCLUSION: Forty percent of PD patients presented with non-motor
      fluctuations, and almost half of these exhibited more than one type. Appropriate
      recognition of levodopa-related fluctuations, both motor and non-motor, can lead
      to treatment modifications in PD patients.

PMID- 22981262
TI  - Subthalamic deep brain stimulation for Parkinson's disease: correlation between
      locations of oscillatory activity and optimal site of stimulation.
AB  - Subthalamic nucleus deep brain stimulation (STN DBS) is an effective surgical
      treatment for Parkinson's disease (PD). Recent studies demonstrated that
      pathological oscillations are seen largely within the dorsolateral portion of the
      STN, which is the same location that predicts optimal therapeutic benefit with
      DBS; however, the precise nature of the relationship between these two phenomena
      remains unclear. The purpose of this study was to explore localization of
      oscillatory activity in relation to the optimal contacts of DBS which results in
      the best motor improvement. We studied 23 PD patients who underwent electrode
      implantation into the STN for motor symptoms. Microelectrode recordings were
      taken from the STN during surgery and neuronal activity was analyzed offline.
      Spectral characteristics were calculated. Clinical outcomes were evaluated pre-
      and post-STN DBS implantation using the Unified Parkinson's Disease Rating Scale
      (UPDRS III). The position of optimal electrode contacts was assessed by
      postoperative magnetic resonance imaging (MRI) and was compared to the location
      of oscillatory activity within the STN as well as its dorsal margin (where STN
      neuronal activity was first detected). Of the total 188 neurons obtained, 51
      (27.1%) neurons showed significant oscillatory activity. Of those, 47 (92.2%)
      were localized in the dorsal portion of the STN. Furthermore, there was no
      significant difference between the averaged coordinates of the position of 40
      optimal contacts and the coordinates of the dorsal margin of the STN. The data
      indicate that the positions of the best contacts correlate with the locations of
      the oscillatory neurons supporting the prediction that stimulation of the
      dorsolateral oscillatory region leads to an effective clinical outcome for STN
      DBS surgery.

PMID- 22981263
TI  - Usefulness of soluble urokinase plasminogen activator receptor to predict repeat
      myocardial infarction and mortality in patients with ST-segment elevation
      myocardial infarction undergoing primary percutaneous intervention.
AB  - The plasma level of the inflammatory biomarker soluble urokinase plasminogen
      activator receptor (suPAR) is an independent predictor of cardiovascular disease
      and all-cause mortality in healthy subjects. The prognostic capability of suPAR,
      its temporal course, and its relation to plasma C-reactive protein (CRP) in
      patients with ST-segment elevation myocardial infarction undergoing primary
      percutaneous intervention (PCI) is unknown. Therefore, the plasma suPAR and CRP
      levels were measured in 296 consecutive patients with ST-segment elevation
      myocardial infarction admitted for primary PCI at baseline and every 6 to 8 hours
      thereafter until the cardiac biomarker levels had peaked. The end points were all
      cause mortality and fatal or nonfatal recurrent myocardial infarction (MI).
      During a median follow-up period of 5.75 years, 69 deaths and 48 nonfatal and 14
      fatal recurrent MIs occurred. All-cause mortality increased significantly from
      8.1% to 41.5% across increasing quartiles of suPAR levels at the end of follow-up
      (log-rank p <0.0001). After adjustment for other independent prognostic factors,
      a highly significant increase was seen in all-cause mortality (hazard ratio 1.45,
      95% confidence interval, 1.19 to 1.76; p <0.001) and recurrent MI (hazard ratio
      1.53, 95% confidence interval 1.16 to 2.01; p <0.01) for each standard deviation
      increment of suPAR levels). In contrast to plasma CRP, the suPAR levels remained
      stable after primary PCI. Furthermore, CRP did not predict mortality or
      reinfarction after adjustment for age and gender (p = 0.34). In conclusion, suPAR
      is a stable plasma biomarker after ST-segment elevation myocardial infarction
      treated with primary PCI that predicts all-cause mortality and recurrent MI.

PMID- 22981264
TI  - Comparison of frequency of postoperative stroke in off-pump coronary artery
      bypass grafting versus on-pump coronary artery bypass grafting versus
      percutaneous coronary intervention.
AB  - The stroke rate after coronary artery bypass grafting (CABG) compared to
      percutaneous coronary intervention (PCI) is generally considered high because
      cardiopulmonary bypass and aortic manipulations are often associated with
      cerebrovascular complications. However, an increasing number of CABGs performed
      without cardiopulmonary bypass (OPCAB) may improve those outcomes. Of 6,323
      patients with multivessel and/or left main coronary artery disease, 3,877
      patients underwent PCI, 1,381 conventional on-pump CABG, and 1,065 OPCAB. Median
      follow-up was 3.4 years. Stroke types were classified as early (onset of stroke
      within 24 hours after revascularization), delayed (within 30 days), and late
      (after 30 days). Propensity score analysis showed that the incidences of early,
      delayed, and late stroke did not differ between PCI and OPCAB (0.65, 95%
      confidence interval 0.08 to 5.45, p = 1.00; 0.36, 0.10 to 1.29, p = 0.23; 0.81,
      0.52 to 1.27, p = 0.72, respectively). In contrast, incidence of early stroke
      after on-pump CABG was higher than after OPCAB (7.22, 1.67 to 31.3, p = 0.01),
      but incidences of delayed and late stroke were not different (1.66, 0.70 to 3.91,
      p = 0.50; 1.18, 0.83 to 1.69, p = 0.73). In conclusion, occurrence of stroke was
      not found to differ in patients after PCI versus OPCAB regardless of onset of
      stroke. Occurrence of early stroke after OPCAB was lower than that after on-pump
      CABG, yet occurrences of delayed and late strokes were similar for the 3
      revascularization strategies.

PMID- 22981265
TI  - Utility of combined assessment of baseline dyssynchrony and its acute improvement
      to predict long-term outcomes after cardiac resynchronization therapy.
AB  - Although left ventricular (LV) mechanical dyssynchrony can predict the response
      to cardiac resynchronization therapy (CRT), the presence of baseline LV
      dyssynchrony might not be the only determinant of the response to CRT. The
      objectives of the present study were to test the hypothesis that a combined
      assessment of baseline LV dyssynchrony and its acute improvement can produce a
      more accurate prediction of the long-term outcomes after CRT. We studied 121
      patients with heart failure undergoing CRT. LV dyssynchrony was determined by
      measuring the anteroseptal-to-posterior wall time delay using the speckle
      tracking radial strain (>=130 ms was predefined as significant) and was assessed
      at baseline and 7 +/- 3 days after CRT. Long-term unfavorable outcome events were
      tracked for 5 years. Acute improvement in LV dyssynchrony of >=33% was predictive
      of the long-term outcome with an area under the curve of 0.67 (p = 0.0024). Using
      this cutoff value, the Kaplan-Meier curve showed that patients with acute
      improvement in LV dyssynchrony experienced fewer cardiovascular events than those
      without (log-rank p = 0.0002). The event-free survival of patients whose baseline
      LV dyssynchrony was >=130 ms and whose acute improvement in LV dyssynchrony was
      >=33% was greater than that of the patients with baseline LV dyssynchrony of
      >=130 ms but with acute improvement in LV dyssynchrony of <33% (88% vs 65%, p =
      0.012). In conclusion, the combined assessment of baseline LV dyssynchrony and
      its acute improvement after CRT produced a more accurate prediction of long-term
      outcomes after CRT.

PMID- 22981266
TI  - Reliability of peak exercise testing in patients with heart failure with
      preserved ejection fraction.
AB  - Exercise intolerance is the primary symptom in patients with heart failure and
      preserved ejection fraction (HFpEF), a major determinant of their decreased
      quality of life, and an important outcome in clinical trials. Although
      cardiopulmonary exercise testing (CPET) provides peak and submaximal diagnostic
      indexes, the reliability of peak treadmill CPET in patients >55 years of age with
      HFpEF has not been examined. Two CPETs were performed in 52 patients with HFpEF
      (70 +/- 7 years old). The 2 tests were separated by an average of 23 +/- 13 days
      (median 22) and performed under identical conditions, with no intervention or
      change in status between visits except for initiation of a placebo run-in. A
      multistep protocol for patient screening, education, and quality control was
      used. Mean peak oxygen consumption was similar on tests 1 and 2 (14.4 +/- 2.4 vs
      14.3 +/- 2.3 ml/kg/min). Correlation coefficients and intraclass correlations
      from the testing days were determined (oxygen consumption, r = 0.85, p <0.001,
      intraclass correlation 0.855; ventilatory anaerobic threshold, r = 0.79, p
      <0.001, intraclass correlation 0.790; ventilation per carbon dioxide slope, r =
      0.87, p <0.001, intraclass correlation 0.864; heart rate, r = 0.94, p <0.001,
      intraclass correlation 0.938). These results challenge conventional wisdom that
      serial baseline testing is required in clinical trials with exercise-capacity
      outcomes. In conclusion, in women and men with HFpEF and severe physical
      dysfunction, key submaximal and peak ET variables exhibited good reliability and
      were not significantly altered by a learning effect or placebo administration.

PMID- 22981267
TI  - Relation of serum lactate dehydrogenase to coronary artery disease.
AB  - Serum lactate dehydrogenase (LDH) is known pathologic marker for a diversity of
      diseases, including myocardial ischemia. Strenuous and enduring physical activity
      can transiently induce a greater total LDH level, still within its normal range.
      To date, however, it has not been determined whether normal-range LDH might be
      inversely associated with coronary artery disease (CAD) in the low-cardiovascular
      risk, physically active, adult population. We conducted a retrospective cohort
      analysis. A total of 5,519 healthy adults aged 34 to 86 years were followed up
      for a mean period of 4.2 years. The cohort incidence of CAD was 6.1% (338 cases)
      from 2001 to 2009. In the present cohort, greater mean LDH levels were
      significantly associated with a greater number of years, days/week, and
      minutes/week of leisure time activity (p = 0.02, p = 0.04, and p = 0.01,
      respectively). These associations were externally validated successfully by
      analysis of all 5,064 healthy participants aged >=40 years with normal-range LDH
      from the 2007 to 2010 National Health and Nutrition Examination Surveys combined.
      For instance, the mean LDH level was significantly greater in those engaged in 6
      to 7 versus 1 to 5 days/wk of vigorous-intensity work activity (138.0 +/- 20.7
      IU/L vs 133.3 +/- 21.7 IU/L, respectively, p = 0.007). In our cohort, the hazard
      ratio for CAD according to the normal total serum LDH tertiles, adjusted for
      multiple risk and protective CAD factors in a Cox proportional hazards model, was
      0.70 (95% confidence interval 0.54 to 0.92) in the greater versus lower tertile
      (p for trend = 0.01). In conclusion, we suggest that increased normal-range total
      serum LDH is associated with reduced short-term risk of CAD outcome in this low
      risk, physically active population.

PMID- 22981269
TI  - Social cognition and the superior temporal sulcus: implications in autism.
AB  - The most common clinical sign of autism spectrum disorders (ASD) is social
      interaction impairment, which is associated with communication deficits and
      stereotyped behaviors. Based on brain-imaging results, our hypothesis is that
      abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD.
      These abnormalities are characterized by decreased grey matter concentration,
      rest hypoperfusion and abnormal activation during social tasks. STS
      anatomofunctional anomalies occurring early across brain development could
      constitute the first step in the cascade of neural dysfunctions underlying
      autism. It is known that STS is highly implicated on social perception
      processing, from perception of biological movements, such as body movements or
      eye gaze, to more complex social cognition processes. Among the impairments that
      can be described in social perception processing, eye gaze perception is
      particularly relevant in autism. Gaze abnormalities can now be objectively
      measured using eye-tracking methodology. In the present work, we will review
      recent data on STS contributions to normal social cognition and its implication
      in autism, with particular focus on eye gaze perception.

PMID- 22981270
TI  - Idiopathic intracranial hypertension: Diagnosis, monitoring and treatment.
AB  - INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a disorder typically
      affecting young, obese women, producing a syndrome of increased intracranial
      pressure without identifiable cause. STATE OF THE ART: Despite a large number of
      hypotheses and publications over the past decade, the etiology of IIH is still
      unknown. There continues to be no evidence-based consensus or formal guidelines
      regarding management and treatment of the disease. Treatment studies show that
      the diagnostic lumbar puncture is a valuable intervention beyond its diagnostic
      importance, and that weight management is critical. However, many questions
      remain, regarding the efficacy of acetazolamide, cerebrospinal fluid (CSF)
      shunting procedures, optic nerve sheath fenestration, and cerebral transverse
      venous sinus stenting. Identification of subgroups of patients at high-risk for
      irreversible visual loss, such as black patients, men, morbidly obese patients,
      and patients with fulminant IIH, helps determine management approaches and refine
      follow-up strategies. PERSPECTIVE: Better understanding of the pathophysiology
      and ongoing clinical trials will hopefully help inform treatment strategies over
      the next few years.

PMID- 22981268
TI  - Rehabilitation of damage to the visual brain.
AB  - Homonymous visual field loss is a common consequence of stroke and traumatic
      brain injury. It is associated with an adverse functional prognosis and has
      implications on day-to-day activities such as driving, reading, and safe
      navigation. Early recovery is expected in around half of cases, and may be
      associated with a return in V1 activity. In stable disease, recovery is unlikely
      beyond 3 and certainly 6 months. Rehabilitative approaches generally target three
      main areas, encompassing a range of techniques with variable success: visual aids
      aim to expand or relocate the affected visual field; eye movement training builds
      upon compensatory strategies to improve explorative saccades; visual field
      restitution aims to improve visual processing within the damaged field itself.
      All these approaches seem to offer modest improvements with repeated practice,
      with none clearly superior to the rest. However, a number of areas are
      demonstrating particular promise currently, including simple web-based training
      initiatives, and work on neuroimaging and learning. The research interest in this
      area is encouraging, and it is to be hoped that future trials can better untangle
      and control for the number of complicated confounds, so that we will be in a much
      better position to evaluate and select the most appropriate therapy for patients.

PMID- 22981271
TI  - Contribution of imaging to the diagnosis of optic neuropathies.
AB  - Magnetic resonance imaging is the modality of choice to investigate patients with
      central nervous system diseases. In patients with optic neuritis, early MRI
      allows positive and differential diagnosis, and gives arguments for prognosis.
      The technique should be adapted for the exploration of visual pathways.
      Inflammatory optic neuritis is characterized by an early signal abnormality
      within the optic nerve, whereas optic nerve MRI is normal in the early phase of
      ischemic optic neuropathy. MRI also detects compressive and infiltrative lesions.
      Meningiomas are characterized by abnormalities within the peri-optical spaces,
      whereas a global increase in the size of the optic nerve is in favor of a glioma.

PMID- 22981272
TI  - When does multiple sclerosis start? Three case reports and a review of the
      literature.
AB  - When does multiple sclerosis start? Multiple sclerosis (MS) is a major cause of
      disability in young adults. Its pathogenesis is not fully understood, although a
      large body of evidence suggests an autoimmune pattern. Autoreactive immune cells
      cross the blood-brain barrier to attack myelin and axons, thus leading to MS
      lesions. Considering the uncertainty concerning the mechanisms, however, it is
      hardly surprising that it is still not possible to pinpoint exactly when the
      disease starts. Yet, the question is of major importance for both patients and
      physicians. Faced with the impossibility of detecting the actual time of disease
      onset, the scientific community has nonetheless made great efforts to diagnose
      the disease as early as possible. In 1983, Poser defined relapsing-remitting MS
      as a chronic disease with at least two relapses. Further criteria (McDonald)
      allowed even earlier diagnosis. In the present review, which also includes three
      case reports, the earliest possible timepoint for making the MS diagnosis is
      discussed.

PMID- 22981273
TI  - Prevalence of ex vivo high on-treatment platelet reactivity on antiplatelet
      therapy after transient ischemic attack or ischemic stroke on the PFA-100((r))
      and VerifyNow((r)).
AB  - BACKGROUND: The prevalence of ex vivo high on-treatment platelet reactivity
      (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic
      attack (TIA) or ischemic stroke is uncertain. METHODS: Platelet function
      inhibition was simultaneously assessed with modified light transmission
      aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately
      high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions
      USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic
      stroke patients. Patients were assessed on aspirin-dipyridamole combination
      therapy (n = 51) or clopidogrel monotherapy (n = 25). RESULTS: On the VerifyNow,
      HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole
      combination therapy (>= 550 aspirin reaction units on the aspirin cartridge).
      Eleven of 25 (44%) patients had HTPR on clopidogrel (>= 194 P2Y12 reaction units
      on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin
      dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI)
      cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the
      collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with
      antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both
      regimens (P < .001). CONCLUSIONS: The prevalence of ex vivo antiplatelet HTPR
      after TIA or ischemic stroke is markedly influenced by the method used to assess
      platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting
      the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with
      the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y
      cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of
      platelet function are warranted to assess whether platelet function monitoring
      predicts clinical outcome in ischemic cerebrovascular disease.

PMID- 22981274
TI  - Benzoic acid and specific 2-oxo acids activate hepatic efflux of glutamate at
      OAT2.
AB  - The liver is the principal source of glutamate in blood plasma. Recently we have
      discovered that efflux of glutamate from hepatocytes is catalyzed by the
      transporter OAT2 (human gene symbol SLC22A7). Organic anion transporter 2 (OAT2)
      is an integral membrane protein of the sinusoidal membrane domain; it is
      primarily expressed in liver and much less in kidney, both in rats and humans.
      Many years ago, Haussinger and coworkers have demonstrated in isolated perfused
      rat liver that benzoic acid or specific 2-oxo acid analogs of amino acids like
      e.g. 2-oxo-4-methyl-pentanoate ('2-oxo-leucine') strongly stimulate release of
      glutamate (up to 7-fold); '2-oxo-valine' and the corresponding amino acids were
      without effect. The molecular mechanism of efflux stimulation has remained
      unclear. In the present study, OAT2 from human and rat were heterologously
      expressed in 293 cells. Addition of 1 mmol/l benzoic acid to the external medium
      increased OAT2-specific efflux of glutamate up to 20-fold; '2-oxo-leucine' was
      also effective, but not '2-oxo-valine'. Similar effects were seen for efflux of
      radiolabeled orotic acid. Expression of OAT2 did not increase uptake of benzoic
      acid; thus, benzoic acid is no substrate, and trans-stimulation can be excluded.
      Instead, further experiments suggest that increased efflux of glutamate is caused
      by direct interaction of benzoic acid and specific 2-oxo acids with OAT2. We
      propose that stimulators bind to a distinct extracellular site and thereby
      accelerate relocation of the empty substrate binding site to the intracellular
      face. Increased glutamate efflux at OAT2 could be the main benefit of benzoate
      treatment in patients with urea cycle defects.

PMID- 22981276
TI  - Rest heart rate and mortality: more physical exercise for the rabbit?

PMID- 22981277
TI  - The heart rate response to adenosine: a simple predictor of adverse cardiac
      outcomes in asymptomatic patients with type 2 diabetes.
AB  - BACKGROUND: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study
      demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted
      heart rate response (HRR, maximum percent change) to adenosine, a simple marker
      of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk.
      METHODS: In DIAD, 518 participants were randomized to screening adenosine
      myocardial perfusion imaging (MPI) and had available data. HRR <20% was
      considered abnormal. The primary endpoint was a composite of nonfatal myocardial
      infarction and cardiac death. RESULTS: During 4.7 +/- 0.9 years of follow-up 15
      (3%) participants experienced the primary outcome. Participants with lower HRR
      experienced more events than those with higher HRR (8%, 3%, 1%, for HRR <20%
      (n=79), 20-39% (n=182) and >= 40% (n=257), respectively, p=0.01). In a Cox
      proportional regression model that included MPI abnormalities and HRR, both were
      independently associated with cardiac events (p for model <0.001). HRR <20% was
      associated with 9-fold increased risk (p=0.007) and moderate/large abnormal MPI
      was associated with 6-fold increased risk (p=0.004). Participants with both
      abnormal MPI and HRR (n=8) were at highest risk for cardiac events (38%) whereas
      those with HRR >= 40%, irrespective of MPI abnormalities (n=234), were at
      extremely low risk (<=1%, log-rank p<0.001). CONCLUSIONS: In DIAD, abnormal HRR
      to adenosine infusion is an independent predictor of cardiac events. This easily
      obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients
      with type 2 diabetes mellitus at increased risk, particularly when associated
      with abnormal MPI, who may warrant further testing and more aggressive
      cardiovascular risk factor management.

PMID- 22981278
TI  - MSCs transfected with hepatocyte growth factor or vascular endothelial growth
      factor improve cardiac function in the infarcted porcine heart by increasing
      angiogenesis and reducing fibrosis.
AB  - BACKGROUND: Cell transplantation and gene therapy have been demonstrated to have
      beneficial effects after a myocardial infarction (MI). Here, we used a large
      animal model of MI to investigate the beneficial effects of mesenchymal stem
      cells (MSCs) transfected with hepatocyte growth factor (HGF) or vascular
      endothelial growth factor (VEGF) genes. METHODS: A porcine MI model was created
      by balloon occlusion of the distal left anterior descending artery for 90 min
      followed by reperfusion. At 1 week after MI, the pigs were infused via the
      coronary vein with saline (n=8), MSCs + AdNull(n=8), MSC+VEGF(n=10), or
      MSC+HGF(n=10). Cardiac function and myocardial perfusion were evaluated by using
      echocardiography and gated cardiac perfusion imaging before and 4 weeks after
      transplantation. Morphometric and histological analyses were performed. RESULTS:
      All cell-implanted groups had better cardiac function than the saline control
      group. There were further functional improvements in the MSC+HGF group,
      accompanied by smaller infarct sizes, increased cell survival, and less collagen
      deposition. Blood vessel densities in the damaged area and cardiac perfusion were
      significantly greater in the MSC+AdNull group than in the saline control group,
      and further increased in the MSC+VEGF/HGF groups. Tissue fibrosis was
      significantly less extensive in the MSC and MSC+VEGF groups than in the saline
      control group and was most reduced in the MSC+HGF group. CONCLUSION: MSCs (alone
      or transfected with VEGF/HGF) delivered into the infarcted porcine heart via the
      coronary vein improved cardiac function and perfusion, probably by increasing
      angiogenesis and reducing fibrosis. MSC+HGF was superior to MSC+VEGF, possibly
      owing to its enhanced antifibrotic effect.

PMID- 22981275
TI  - Structure and function of the beta subunit of voltage-gated Ca2+ channels.
AB  - The voltage-gated Ca2+ channel beta subunit (Ca(v)beta) is a cytosolic auxiliary
      subunit that plays an essential role in regulating the surface expression and
      gating properties of high-voltage activated (HVA) Ca2+ channels. It is also
      crucial for the modulation of HVA Ca2+ channels by G proteins, kinases, Ras
      related RGK GTPases, and other proteins. There are indications that Ca(v)beta may
      carry out Ca2+ channel-independent functions. Ca(v)beta knockouts are either non
      viable or result in a severe pathophysiology, and mutations in Ca(v)beta have
      been implicated in disease. In this article, we review the structure and various
      biological functions of Ca(v)beta, as well as recent advances. This article is
      part of a Special Issue entitled: Calcium channels.

PMID- 22981279
TI  - Early clinical presentation of diffuse, severe, multi-district atherosclerosis
      after radiation therapy for Hodgkin lymphoma.

PMID- 22981280
TI  - Is a score of 10 or greater on the Beck Depression Inventory equivalent to
      clinically diagnosed depression?

PMID- 22981281
TI  - Clinical implications of biological markers in Pancreatic Ductal Adenocarcinoma.
AB  - Pancreatic Ductal Adenocarcinoma (PDAC) is a malignant neoplasm and is the fourth
      leading cause of cancer-related deaths in US with a 5-year survival rate less
      than 5%. Surgery is the only potentially curative treatment even though the
      result is a palliation in the majority of cases and the majority of lesions are
      lately diagnosed. Progression from normal pancreatic epithelium to metastatic
      disease is now a well-characterized sequence of events. Research has shown that
      pancreatic cancer is fundamentally a genetic disease with several biological
      pathway implied in apoptosis, cell proliferation and self-sufficiency in growth
      signaling, but how those findings could be applied in daily clinical practice
      remain unknown. Several studies tried to characterize diagnostic and prognostic
      biomarkers in PDAC to make it possible an earlier diagnosis, guarantee a more
      effective treatment and reach a better prognosis even though the results remain
      contrasting. The main limit of the published researches is the small number of
      patients studied, but even the heterogeneity of the used methods of analysis.
      Examining critically the research of the last years future trials may be
      addressed toward a translational models integrating "the bench and the bed" with
      the clinical experience and drive the basic research toward the clinical
      applications.

PMID- 22981282
TI  - [Validation of a questionnaire to assess patient safety culture in Spanish
      Primary Health Care professionals].
AB  - OBJECTIVE: [corrected] To validate a tool to measure patient safety culture in
      Spanish primary care professionals. METHODS: Medical Office Survey on Patient
      Safety Culture (MOSPSC), from the Agency for Healthcare and Research in Quality
      (AHRQ). The process has been performed in five steps: original version
      traslation, conceptual equivalence evaluation, acceptability and viability
      assessment, content validity and questionnaire test and response analysis and
      psichometric properties assessment. SETTING: Primary care. SUBJECTS: 185 Primary
      care professionals from different Spanish regions represented the sample test.
      MAIN OUTCOME MEASURES: Frecuency, response pattern and discrimination power of
      each item. Cronbach's alpha coefficient and dimensions obtained through factor
      analysis. RESULTS: 17, 8% of respondents answered all the items and 28, 7% of
      them did not answer, or answered the option "Don't know/Does not apply", to one
      to four items. All the sentences, with only one exception, present discrimination
      capacity. Cronbach's alpha coefficient results 0,96 and information is sumarized
      in 15 factors obtaining the same items in 7 of the total 12 factors in the
      original questionnaire. CONCLUSIONS: Traslated, adapted, extended and validated
      AHRQ questionnaire is, in this setting, a reliable and useful instrument and it
      must be used for international comparisons.

PMID- 22981283
TI  - [Universal health cover, fairness and sympathy. Three cases to observe].

PMID- 22981284
TI  - Room temperature ionic liquids enhanced the speciation of Cr(VI) and Cr(III) by
      hollow fiber liquid phase microextraction combined with flame atomic absorption
      spectrometry.
AB  - A new method for the speciation of Cr(VI) and Cr(III) based on enhancement effect
      of room temperature ionic liquids (RTILs) for hollow fiber liquid phase
      microextraction (HF-LPME) combined with flame atomic absorption spectrometry
      (FAAS) was developed. Room temperature ionic liquids (RTILs) and
      diethyldithiocarbamate (DDTC) were used enhancement reagents and chelating
      reagent, respectively. The addition of room temperature ionic liquids led to 3.5
      times improvement in the determination of Cr(VI). In this method, Cr(VI) reacts
      with DDTC yielding a hydrophobic complex, which is subsequently extracted into
      the lumen of hollow fiber, whereas Cr(III) is remained in aqueous solutions. The
      extraction organic phase was injected into FAAS for the determination of Cr(VI).
      Total Cr concentration was determined after oxidizing Cr(III) to Cr(VI) in the
      presence of KMnO(4) and using the extraction procedure mentioned above. Cr(III)
      was calculated by subtracting of Cr(VI) from the total Cr. Under optimized
      conditions, a detection limit of 0.7 ng mL(-1) and an enrichment factor of 175
      were achieved. The relative standard deviation (RSD) was 4.9% for Cr(VI) (40 ng
      mL(-1), n=5). The proposed method was successfully applied to the speciation of
      chromium in natural water samples with satisfactory results.

PMID- 22981285
TI  - Degradation of gamma-HCH spiked soil using stabilized Pd/Fe0 bimetallic
      nanoparticles: pathways, kinetics and effect of reaction conditions.
AB  - This study investigates the degradation pathway of gamma-hexachlorocyclohexane
      (gamma-HCH) in spiked soil using carboxymethyl cellulose stabilized Pd/Fe(0)
      bimetallic nanoparticles (CMC-Pd/nFe(0)). GC-MS analysis of gamma-HCH degradation
      products showed the formation of pentachlorocyclohexene, tri- and di
      chlorobenzene as intermediate products while benzene was formed as the most
      stable end product. On the basis of identified intermediates and final products,
      degradation pathway of gamma-HCH has been proposed. Batch studies showed complete
      gamma-HCH degradation at a loading of 0.20 g/L CMC-Pd/nFe(0) within 6h of
      incubation. The surface area normalized rate constant (k(SA)) was found to be 7.6
      * 10(-2) L min(-1)m(-2). CMC-Pd/nFe(0) displayed ~ 7-fold greater efficiency for
      gamma-HCH degradation in comparison to Fe(0) nanoparticles (nFe(0)), synthesized
      without CMC and Pd. Further studies showed that increase in CMC-Pd/nFe(0) loading
      and reaction temperature facilitates gamma-HCH degradation, whereas a declining
      trend in degradation was noticed with the increase in pH, initial gamma-HCH
      concentration and in the presence of cations. The data on activation energy (33.7
      kJ/mol) suggests that gamma-HCH degradation is a surface mediated reaction. The
      significance of the study with respect to remediation of gamma-HCH contaminated
      soil using CMC-Pd/nFe(0) has been discussed.

PMID- 22981286
TI  - Removal of boron from wastewater by the hydroxyapatite formation reaction using
      acceleration effect of ammonia.
AB  - The mechanism was discussed for the removal of boron by the hydroxyapatite (HAp)
      formation reaction using Ca(OH)(2) and (NH(4))(2)HPO(4) in room temperature. Time
      required to remove boron was 20 min by adding Ca(OH)(2) and (NH(4))(2)HPO(4) for
      the remaining boron to below 1mg/L. The removal rate of boron was controlled by
      the HAp precipitate formation and the presence of ammonia. From the XRD patterns
      and SEM images, HAp could be confirmed in the precipitate product. The reaction
      between borate ions and calcium hydroxide was accelerated by dehydration with
      ammonia; the borate-calcium hydroxide compound coprecipitated with resulting HAp.
      Although the removal of boron decreased in the presence of sulfate, phosphate,
      and aluminum, these effects could be prevented by adding excess Ca(OH)(2).
      Interference of fluoride ions was eliminated by adding Al(3+). Sodium alpha
      olefin sulfonate was the most effective coagulant for HAp precipitation. The
      proposed boron removal method has several advantages about treating time and
      ability of boron removal. The method was successfully applied to the real hot
      spring wastewater.

PMID- 22981287
TI  - Novel Hg2+-imprinted polymers based on thymine-Hg2+-thymine interaction for
      highly selective preconcentration of Hg2+ in water samples.
AB  - A novel functional monomer T-IPTS, 3-isocyanatopropyltriethoxysilane (IPTS)
      bearing thymine (T) bases, was synthesized for imprinting Hg(2+). Then a novel
      Hg(2+) ionic imprinted polymers (IIPs) based on thymine-Hg(2+)-thymine (T-Hg(2+)
      T) interactions, i.e. Hg-IIPs-T, were prepared by sol-gel process for the first
      time in this work. The Hg-IIPs-T exhibited excellent selectivity towards Hg(2+)
      over Cd(2+), Zn(2+) Pb(2+), Co(2+), Mn(2+), Mg(2+) and Ca(2+), due to the
      specific T-Hg(2+)-T interactions with high selectivity and high affinity.
      Accordingly, Hg-IIPs-T were used as solid-phase extraction (SPE) sorbents for
      preconcentration of trace Hg(2+) in water samples, and satisfactory recoveries
      ranging from 95.2 to 116.3% were obtained. Also, under optimized conditions,
      preconcentration factor and detection limit were achieved of 200 and 0.03 MUg L(
      1), respectively. The IIPs-T-SPE proved to be a rapid and high-effective cleanup
      and enrichment method for trace Hg(2+) in water samples. More importantly, these
      results indicated that devising and synthesizing new functional monomers tailor
      made for template would become a general promising way to improve the selectivity
      and stability of IIPs.

PMID- 22981288
TI  - Interleukin 24: mechanisms and therapeutic potential of an anti-cancer gene.
AB  - Interleukin 24 (mda-7/IL-24) has been classified as an anti-cancer gene for its
      ability to selectively induce cell death in cancer cells while having little to
      no effect on normal cells. Although the exact mechanisms by which IL-24 functions
      have not been completely elucidated, several pathways have consistently been
      identified: endoplasmic reticulum stress, ceramide-mediated events, and the
      generation of reactive oxygen species. In addition to these mechanistic analyses,
      significant progress has also been reported regarding the clinical potential of
      this anti-cancer gene. For example, many groups are utilizing mda-7/IL-24 in
      combination with other cancer therapies. This review examines the current
      research and potential future of this important anti-cancer gene.

PMID- 22981289
TI  - Oxidative stress in patients with essential hypertension: a comparison of dippers
      and non-dippers.
AB  - BACKGROUND: Oxidative stress seems to play an important role in the
      pathophysiology of essential hypertension. We aimed to examine serum MDA, NO, 8
      OHdG, ADMA, NT, CoQ10 and TAC as biomarkers of oxidative stress in dipper and non
      dipper hypertensive patients. METHODS: Eighteen dipper hypertensives, 20 non
      dipper hypertensives and 22 healthy control subjects were included in the study.
      Clinical assessment and ambulatory blood pressure monitoring were performed in
      patients. Serum MDA, TAC and NO levels were measured by using spectrophotometric
      methods. CoQ10 levels were measured by HPLC method. 8-OHdG, ADMA and NT were
      quantitated by ELISA methods. RESULTS: MDA levels were significantly higher in
      dipper and non-dipper groups compared to controls (p<0.05 and p<0.01,
      respectively). TAC levels were found at low level in patients dipper and non
      dipper patients compared to control group (p<0.01). Higher ADMA and NT levels but
      lower CoQ10 levels were found in non-dipper group compared to healthy controls
      (p<0.01, p<0.05, and p<0.05, respectively). ADMA levels were found higher in non
      dipper group than those of dipper group (p<0.01). DISCUSSION: Increased ADMA, NT
      levels and decreased CoQ10 levels in non-dipper hypertensive patients might
      indicate more severe oxidative stres compared with dipper hypertensive patients,
      which plays an important role in the development of cardiovascular diseases.
      Increased MDA and reduced TAC levels might be considered as prospective
      prognostic markers of the development of cardiovascular diseases in dipper and
      non-dipper hypertensive patients.

PMID- 22981290
TI  - The impact of a vaccination campaign against hepatitis B on the further decrease
      of hepatitis B virus infection in a southern Italian town over 14 years.
AB  - BACKGROUND: Hepatitis B virus infection has decreased in Italy. The aims of this
      study were to identify changes, if any, in the epidemiological pattern of HBV
      infection in a southern Italian town first surveyed in 1996 and to assess the
      effectiveness of vaccination campaign against hepatitis B. METHODS: In 2010,
      subjects were selected from the census by a systematic 1:4 random sampling
      procedure. Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core
      antigen (anti-HBc) were detected by ELISA. Associations (odds ratios) linking
      exposure to hepatitis B virus infection to potential risk factors were estimated
      by univariate and multivariate analyses. RESULTS: Of the 1100 eligible subjects,
      1020 (92.0%) agreed to participate. The prevalences of HBsAg (0.6%) and anti-HBc
      (15.2%) were significantly lower than in 1996 (0.8% and 21.5%) (p<0.01). No
      subject below 30 years of age (those that had been targeted for compulsory
      immunization) had been exposed to HBV infection. At multiple logistic regression
      analysis, age>45 years (OR=9.8; 95% CI=5.1-18.7) and past use of glass syringes
      (OR=1.9; 95% CI=1.2-3.1) independently predicted the likelihood of anti-HBc
      positivity. CONCLUSIONS: These results, albeit obtained in a small town and thus
      not generalizable, confirm the continuous decreasing trend of HBV infection and
      demonstrate the effectiveness of the Italian hepatitis B vaccination program.

PMID- 22981291
TI  - Increasing prevalence of hypertension in low income residents within Louisiana
      State University Health Care Services Division Hospital System.
AB  - BACKGROUND: Hypertension risk in local areas may vary from national estimates;
      however, the data on the prevalence of hypertension in some local areas are
      limited. We investigate the trend in the prevalence of hypertension in Louisiana
      from 2000 to 2009. METHODS: We conducted a retrospective study among the subjects
      aged >= 20 years who received medical care from the Louisiana State University
      Health Care Services Division (LSUHCSD) hospital system during 2000-2009.
      Hypertensive cases were identified by using ICD-9 codes. The annual hypertension
      prevalence was calculated as the number of unique hypertensive individuals during
      the year divided by the number of unique individuals visiting the LSUHCSD
      hospital during the year. RESULTS: The age-standardized prevalence of
      hypertension in LSUHCSD hospital patients aged >= 20 years increased by 49.4%
      during 2000-2009, from 24.1% in 2000 to 36.0% in 2009. The rise in age
      standardized prevalence of hypertension from 2000 to 2009 occurred in both men
      (from 20.1% to 32.8%) and women (from 26.8 % to 38.3%), and in White (from 20.1%
      to 33.0%), African (from 27.4% to 37.6%) and other race Americans (from 14.9% to
      22.3%). The age-standardized prevalence of hypertension was higher in women than
      in men, and higher in African Americans than in White and other race Americans.
      CONCLUSION: The annual prevalence of hypertension has dramatically increased from
      2000 to 2009 in both men and women and in all races of the population served by
      the LSUHCSD hospitals.

PMID- 22981292
TI  - Early nutrition patterns and diseases of adulthood: a plausible link?
AB  - In the last decades several studies tested the hypothesis that at early
      development stages certain foods or nutrients, in specific amounts, fed during
      limited sensitive periods, may determine an endocrine metabolic asset leading to
      clinical alterations that take place decades later (early nutritional programming
      of long term health). Evidence is mounting for programming effects of infant
      feeding. Observational studies indicate that breast feeding, relative to formula
      feeding, reduces the risk for obesity at school age by about 20% even after
      adjustment for biological and sociodemographic confounders. Moreover,
      breastfeeding is constantly associated with increased neurodevelopmental scores
      up to early adulthood, while its outcome in terms of delayed decay of brain
      function is still unknown. Besides the environment surrounding breastfeeding,
      specific nutrients within human milk may play a direct role. With the
      introduction of solids the major changes in diet are represented by the sudden
      decrease of fat intake from 50 to 30% of total energy. A protein excess, commonly
      found throughout all European Countries, has been associated to a higher risk of
      adiposity in early childhood, as confirmed by first reports from a large European
      trial. The amount of fat does not seem to be associated with later adiposity,
      while its quality may affect blood lipoproteins, blood pressure and
      neurodevelopmental performance. Early intake of dietary fibers might also have
      beneficial effects. Epidemiologic data show that episodes of rapid growth (growth
      acceleration hypothesis), whichever the dietary habits, are associated with later
      unfavorable health conditions and should be prevented.

PMID- 22981293
TI  - Poor growth in an infant with cystic fibrosis due to an antenatal perforation and
      incomplete bowel obstruction.

PMID- 22981294
TI  - Growth retardation and reduced growth hormone secretion in cystic fibrosis.
      Clinical observations from three CF centers.
AB  - OBJECTIVE: Growth delay in cystic fibrosis is frequent and is usually the result
      of several interacting causes. It most often derives from severe respiratory
      impairment and severe malabsorption. There are however patients whose clinical
      condition is not severe enough to be held accountable for this phenomenon. We
      aimed at describing patients who showed growth delay, who were not affected by
      severe pulmonary disease or malabsorption and who, when tested, showed a reduced
      GH secretion after stimulation with conventional agents. We noticed a
      disproportionately large prevalence of growth hormone (GH) release deficit (GHRD)
      in pediatric cystic fibrosis (CF) patients. PATIENTS AND METHODS: We examined all
      patients under our care in the period 2006-11, who were older than 5 and younger
      than 16 years old. We focussed on those who fell below the 3rd height percentile,
      or whose growth during the previous 18 months faltered by >2SD, and who did not
      present clinical conditions that could reasonably explain their failure to
      thrive. These patients were subjected to standard GH provocative tests. RESULTS:
      Out of 285 who matched the age criterion, 33 patients also matched the height
      percentile criterion. While 15/33 suffered clinical conditions that could
      reasonably explain their failure to thrive, 18/33 underwent GH release
      provocative tests and 12/18 showed a release deficit. CONCLUSIONS: We conclude
      that impaired GH secretion is more frequent among CF patients compared to the
      prevalence of GH deficiency in the general population and that GH release
      impairment may be an independent cause of growth delay in CF. Our findings are in
      agreement with recent studies that have described low GH levels in CF piglets and
      in neonates with CF [1].

PMID- 22981295
TI  - [Idiopathic intracranial hypertension: stent or not].
AB  - The pathogenesis and treatment paradigm for idiopathic intracranial hypertension
      (IIH) are controversial. Transverse sinus stenosis is seen in the majority of
      patients with IIH and appears to play a role in the disease process. The debate
      continues as to whether transverse sinus stenosis is a primary or secondary
      process relative to raised intracranial pressure. While the role of transverse
      sinus stenosis in IIH pathogenesis remains controversial, modeling studies
      suggest that stent placement within a transverse sinus stenosis with a
      significant pressure gradient should decrease cerebral venous pressure, improve
      CSF resorption in the venous system, and thereby reduce intracranial (CSF)
      pressure, improving the symptoms of IIH and reducing papilledema. Beside the
      classical surgical treatments, venous sinus stenting could be a treatment option
      for many patients with IIH. However, additional work, preferably controlled
      prospective studies, needs to be performed to prove its safety and efficacy. The
      goal of this article is to review the current literature on dural venous sinus
      stenting.

PMID- 22981297
TI  - [POEMS syndrome revealed unusually early with unexplained hepatic and peritoneal
      granulomas: to an associated malignant lymphoma?].

PMID- 22981296
TI  - The bedside examination of the vestibulo-ocular reflex (VOR): an update.
AB  - Diagnosing dizzy patients remains a daunting challenge to the clinician in spite
      of modern imaging and increasingly sophisticated electrophysiological testing.
      Here we review the major bedside tests of the vestibulo-ocular reflex and how,
      when combined with a proper examination of the other eye movement systems, one
      can arrive at an accurate vestibular diagnosis.

PMID- 22981298
TI  - When does Parkinson's disease begin? From prodromal disease to motor signs.
AB  - Cardinal motor features of Parkinson's disease (PD) appear when about half of the
      nigral dopamine neurons have disappeared. Based on extrapolations from post
      mortem and imaging studies, the delay between the onset of dopamine denervation
      and the appearance of motor signs ranges from 5 to 20years. According to Braak
      and co-workers, motor symptoms only appear at stage III of PD, while the
      neurodegenerative process begins earlier in the olfactory bulb and lower brain
      stem. In addition to the cardinal motor features, non-motor signs are
      increasingly being recognized in PD. Some of them, mainly olfactory disturbances,
      rapid-eye-movement sleep behaviour disorder and autonomic dysfunction, are
      already present in the early disease stages and may precede the onset of motor
      signs by up to four decades. These non-motor signs are related to widespread
      extranigral and even extracerebral degeneration, and have been considered risk
      factors for many years. Indeed, recent evidence suggests that they may be
      prodromal manifestations of PD. From the perspective of future disease-modifying
      or neuroprotective treatments, combining prodromal non-motor signs and
      paraclinical investigations may help to further develop reliable tools for early
      diagnosis of PD before the onset of its cardinal motor features.

PMID- 22981299
TI  - Designing primate models to assess the prodromal phase of Huntington's disease.
AB  - Huntington's disease (HD) is an inherited autosomal-dominant neurodegenerative
      disorder characterized by frontal-type cognitive deficits, involuntary choreiform
      movements and progressive neuronal degeneration, primarily affecting the caudate
      putamen complex. There is currently no effective therapy for this disorder.
      Numerous efforts are directed towards the search and validation of new therapies
      to prevent or slow down disease progression. To this end, different animal
      models, including in nonhuman primates, have been developed to mimic the early
      phase of neuronal dysfunction that precedes degeneration in this pathology. The
      present manuscript provides a critical evaluation of existing and currently
      developed primate models of Huntington's disease. Their pertinence and
      predictability for the evaluation of innovative therapeutic strategies are also
      discussed.

PMID- 22981300
TI  - Atypical forms of optic neuritis.
AB  - Inflammatory optic neuritis (ON) represents a frequent clinical situation in
      neurology and ophthalmology. The most current etiology is multiple sclerosis (MS)
      but, when MRI and Cerebrospinal fluid (CSF) analyses are normal, ON is usually
      considered as "idiopathic" with a suspected viral etiology. In rare cases, a
      systemic disease such as sarcoidosis, lupus or Sjogren syndrome may be diagnosed.
      In several cases either a recurrence or a myelitis may occur without any argument
      for MS. In the first case, it corresponds to relapsing inflammatory optic
      neuritis (RION) and in the second case to neuromyelitis optica (NMO). In the
      present paper, the author successively presents the various clinical situations
      and complementary findings (infectious, vasculitis, NMO or idiopathic) that can
      lead to a differential diagnosis of MS in a context of ON.

PMID- 22981301
TI  - Cortical and sub-cortical control of saccades and clinical application.
AB  - Saccades allow object of interest that are perceived by the peripheral retina to
      be displayed on the fovea, a small central retinal area of maximum visual
      accuracy. Saccades may be generated under a large variety of circumstances, from
      reflexive like saccades (e.g. towards a threatening visual cue) to highly
      volitional saccades (e.g. towards the memorized location of a no longer present
      visual cue). These different contexts correspond to different complexities of
      decision-making processes and, on a behavioral aspect, to saccades with different
      latencies, and to the involvement of different cortical areas. However, whatever
      their type, saccades need to be fast, in order to avoid any persaccadic visual
      blur, and accurate since the fovea represents less than 1 degrees  of visual
      angle. This combination of accuracy and velocity is achieved thanks to a
      collaboration of brainstem and cerebellar oculomotor structures. The basic neural
      structures involved in these processes are reviewed, a special emphasis being
      given to clinically relevant mechanisms.

PMID- 22981302
TI  - [Suspected adverse events to measles, mumps and rubella vaccine reported to the
      Community of Valencia Pharmacovigilance Centre].
AB  - INTRODUCTION: A Pharmacovigilance system is an important tool for post-marketing
      monitoring on vaccine safety. Measles, mumps, rubella (MMR) vaccine is a combined
      vaccine of live attenuated virus. Since its approval, and although the adverse
      events are considered generally mild, the vaccine has been widely questioned for
      the controversies arising around its safety. Our objective was to describe
      suspected adverse events related to MMR vaccine reported to the Valencian
      Pharmacovigilance Centre. MATERIAL AND METHODS: Descriptive study from cases
      reported between May 15th, 2005 and May 15th, 2010. After grouping the suspected
      adverse events by diagnostic criteria, a descriptive analysis of variables was
      performed. RESULTS: After 545,830 doses administered, 96 notifications were
      reported (1.76 notifications/100,000 doses) including 181 adverse events. Fever
      (42.7%) and local inflammation (36.5%) were the most reported events. There were
      8.3% notifications classified as severe. Recovery was complete in all cases.
      CONCLUSIONS: The suspected adverse events reported coincided with those described
      in the Summary of Product Characteristics of the vaccine. The frequency of
      reports was lower than previously published estimates. Despite the limitations,
      the data obtained allowed us to conclude that MMR vaccine has a good safety
      profile, according to previously published studies.

PMID- 22981303
TI  - High-precision control of LSRM based X-Y table for industrial applications.
AB  - The design of an X-Y table applying direct-drive linear switched reluctance motor
      (LSRM) principle is proposed in this paper. The proposed X-Y table has the
      characteristics of low cost, simple and stable mechanical structure. After the
      design procedure is introduced, an adaptive position control method based on
      online parameter identification and pole-placement regulation scheme is developed
      for the X-Y table. Experimental results prove the feasibility and its priority
      over a traditional PID controller with better dynamic response, static
      performance and robustness to disturbances. It is expected that the novel two
      dimensional direct-drive system find its applications in high-precision
      manufacture area.

PMID- 22981304
TI  - Evaluation of reliability of computerized neurobehavioral tests in Korean
      children.
AB  - Neurobehavioral tests are among the most efficient methods of identifying the
      adverse health effects of neurotoxicants. The reliability of neurobehavioral
      tests may be affected by racial or cultural backgrounds, but the widely used
      computerized neurobehavioral tests have been developed and standardized for
      Western children. It is thus necessary to assess the reliability of the existing
      computerized neurobehavioral tests for Korean children. For this reason, 254
      healthy 7- to 8-year-old Korean children completed a neurobehavioral test-retest,
      with the test and retest held two months apart. Six neurobehavioral test items
      adapted from Korean Computerized Neurobehavioral Tests (KCNT) and modified to
      match the children's ability levels: Simple Reaction Time, Choice Reaction Time,
      Color Word Vigilance, Addition, Symbol Digit, and Finger Tapping Speed. The test
      reliability was assessed using the Pearson product-moment correlation coefficient
      (r) and the intraclass correlation coefficient (ICC). The ICCs ranged from 0.46
      to 0.84 and were very similar to the Pearson coefficients. High reliability was
      detected in Symbol Digit (r=0.84, ICC=0.83), followed by the Finger Tapping Speed
      of the dominant hand (r=0.67, ICC=0.67) and of the non-dominant hand (r=0.65,
      ICC=0.65). The study findings suggest that the reliability of most computerized
      neurobehavioral tests is appropriate for epidemiological researches on Korean
      children, and that Symbol Digit and Finger Tapping Speed are more satisfactory
      bases for the periodic examination of neurobehavioral performance. These findings
      can also be useful in the future assembly of a neurobehavioral test battery, by
      providing more stable neurobehavioral test items for Korean children.

PMID- 22981305
TI  - Pain in the air: successful computed tomography-guided aspiration in a case of
      spontaneous pneumorrhachis.

PMID- 22981306
TI  - Development of a cross-over randomized trial method to determine the
      acceptability and safety of novel ready-to-use therapeutic foods.
AB  - OBJECTIVE: To develop a method for determining the acceptability and safety of
      ready-to-use therapeutic foods (RUTF) before clinical trialing. Acceptability was
      defined using a combination of three consumption, nine safety, and six preference
      criteria. These were used to compare a soy/maize/sorghum RUTF (SMS-RUTFh),
      designed for the rehabilitation of human immunodeficiency virus/tuberculosis
      (HIV/TB) wasted adults, with a peanut-butter/milk-powder paste (P-RUTF; brand:
      Plumpy'nut) designed for pediatric treatment. METHODS: A cross-over, randomized,
      controlled trial was conducted in Kenya. Ten days of repeated measures of product
      intake by 41 HIV/TB patients, >18 y old, body mass index (BMI) 18-24 kg . m(-2),
      250 g were offered daily under direct observation as a replacement lunch meal.
      Consumption, comorbidity, and preferences were recorded. RESULTS: The study arms
      had similar age, sex, marital status, initial BMI, and middle upper-arm
      circumference. No carryover effect or serious adverse events were found. SMS
      RUTFh energy intake was not statistically different from the control, when
      adjusted for BMI on day 1, and the presence of throat sores. General preference,
      taste, and sweetness scores were higher for SMS-RUTFh compared to the control (P
      < 0.05). Most consumption, safety, and preference criteria for SMS-RUTFh were
      satisfied except for the average number of days of nausea (0.16 versus 0.09 d)
      and vomiting (0.04 versus 0.02 d), which occurred with a higher frequency (P <
      0.05). CONCLUSION: SMS-RUTFh appears to be acceptable and can be safely
      clinically trialed, if close monitoring of vomiting and nausea is included. The
      method reported here is a useful and feasible approach for testing the
      acceptability of ready-to-use foods in low income countries.

PMID- 22981307
TI  - [Role of French hospital claims databases from care units in epidemiological
      studies: the example of the "Cohorte Enfant Scanner" study].
AB  - BACKGROUND: The "Cohorte Enfant Scanner", a study designed to investigate the
      risk of radiation-induced cancer after childhood exposure to CT (computed
      tomography) examinations, used clinical information contained in the "programme
      de medicalisation des systemes d'information" (PMSI) database, the French
      hospital activities national program based upon diagnosis related groups (DRG).
      However, the quality and adequacy of the data for the specific needs of the study
      should be verified. The aim of our work was to estimate the percentage of the
      cohort's children identified in the PMSI database and to develop an algorithm to
      individualize the children with a cancer or a disease at risk of cancer from
      medical diagnoses provided by the DRGs database. METHODS: Of the 1519 children
      from the "Cohorte Enfant Scanner", who had had a CT scan in the radiology
      department of a university hospital in 2002, a cross linkage was performed with
      the DRGs database. All hospitalizations over the period 2002-2009 were taken into
      account. An algorithm was constructed for the items "cancer" and "disease at risk
      for cancer" on a sample of 150 children. The algorithm was then tested on the
      entire population. RESULTS: Overall, 74% of our population was identified in the
      DRGs database. The algorithm individualized cancer diagnoses with 91% sensitivity
      (95% confidence interval [95%CI]: 86%; 97%) and 98% specificity (95%CI: 97%; 99%)
      and 86% positive predictive value (95%CI: 80%; 93%). For the diagnosis of disease
      at risk for cancer, the sensitivity, specificity and positive predictive value
      were respectively 91% (95%CI: 84%; 98%), 94% (95%CI: 92%; 95%) and 52% (95%CI:
      43%; 61%). CONCLUSION: The DRG database identified with excellent sensitivity and
      specificity children with diagnoses of cancer or disease at risk for cancer.
      Hence, potential confounding factors related to the disease of the child can be
      taken into account for analyses performed with the cohort.

PMID- 22981308
TI  - [Haematological malignancies (HM) in Basse-Normandie (BN): incidence and clinical
      and biological characteristics over the period 1997-2005 in patients less than 25
      years old].
AB  - BACKGROUND: The study was designed to present the incidence of all the
      haematological malignancies (HM) in Basse-Normandie (BN) over the period 1997 to
      2005 in patients less than 25 years old. BN is an administrative region in the
      North-West of France, composed of three departments: Calvados, Manche and Orne.
      We extracted data from the Registre regional des hemopathies malignes de Basse
      Normandie, a French registry which belongs to the Association of the French
      Cancer Registries (Francim). METHODS: All the HM were coded using the third
      edition of the International classification for oncologic diseases (ICD-O-3). We
      compared the clinical and biological descriptive data in patients less than 15
      years old to those of young adults (15-24 years old). RESULTS: A total of 305 new
      cases of HM were recorded over the period 1997 to 2005. HM were more frequent in
      men (168 cases) than in women (137 cases). Patients less than 25 years old
      accounted for 4.1% of all HM cases, whereas patients less than 15 years old and
      young adults (15-24 years old) represented 2.2% and 1.9% of all cases,
      respectively. In patients less than 25 years old, the overall world-standardized
      incidence rates (WSR) were 7.67/100,000 (95% CI: 6.31-9.04) in BN (8.08 [6.15
      10.02] for men and 7.24 [5.31-9.17] for women). In patients less than 15years,
      the overall WSR was 7.38/100,000 (6.23-8.52), with no difference between boys
      (7.57) and girls (7.17). Acute lymphoblastic leukaemia (ALL) was the most
      frequent HM, WSR=4.02/100,000 (3.16-4.88) (4.30 [3.08-5.53] in men, 3.73 [2.52
      4.93] in women), with similar clinical and biological criteria between patients
      less than 15 years and young adults. In young adults, the overall WSR was
      8.21/100,000 (7.47-8.96), similar between men and women (9.02 [7.93-10.12] and
      7.37 [6.35-8.38], respectively). Their highest WSR was obtained for Hodgkin
      lymphomas (HL): 3.37/100,000 (2.89-3.85), similar between men (3.49 [2.8-4.17])
      and women (3.25 [2.58-3.93]). The study did not show any significant difference
      between the Calvados, Manche and Orne departments (except for HL, which seems
      more frequent in Manche department for 15-24 years old cases). There was no
      evidence of an increased risk for ALL in the subdistricts Beaumont-Hague and Les
      Pieux, which respectively have a nuclear waste reprocessing plant and a nuclear
      power plant on their territory. The subtype of HM was dependent on age whereas
      clinical and biological data were the same, whatever the age. CONCLUSION: These
      results contribute to HM monitoring in an area where the nuclear industry is
      present and to improve the organization and follow-up of medical care.

PMID- 22981309
TI  - Consumption of psychoactive substances among 535 women entering a Lyon prison
      (France) between June 2004 and December 2008.
AB  - BACKGROUND: In France, recent data on the consumption of psychoactive substances
      (PASs) among women entering prison are virtually nonexistent. The objective of
      this study was to describe the characteristics of female entrants at Montluc
      prison in Lyon (France) and to estimate their PAS consumption. METHODS: Between
      June 1, 2004 and December 31, 2008, of 841 women entering the Lyon correctional
      facility, 535 had an entrance interview, conducted by a nurse, during which a
      questionnaire was systematically proposed; 306 detainees did not have this
      interview and could not be included in the study because of an immediate transfer
      to another prison or emergency hospitalization. Socioeconomic and incarceration
      characteristics, PAS consumption, as well as consumption level (occasional,
      regular, abusive or dependence) and psychological distress of the 535 interviewed
      detainees were systematically noted. This psychological distress was defined by
      the presence in the entrant talks or behavior suggesting clinical symptoms such
      as anxiety, depression, delusion, delirium, and mood or behavior disorders.
      Descriptive analysis was undertaken with the Chi(2) test and Fisher's exact test
      for differences between the proportions observed. RESULTS: The average age of the
      534 responding detainees was 31.5 years; 59.2% had had no ongoing professional
      activity in the 12 months prior to incarceration, and 21.6% had already been
      imprisoned before; 37.5% of the entrants reported dependence on tobacco and 13.7%
      on alcohol; 6.6% reported regular, abusive use or dependence on cannabis, 20.4%
      on psychotropic medications, and 7.7% on other drugs (heroin, cocaine, synthetic
      drugs) in the 6 months preceding their incarceration; 39.2% of the consumers at
      risk reported using at least two substances; 7.1% of detainees were on opioid
      substitution treatment. A multiple correspondence factor analysis was used to
      note specific characteristics of three groups of PAS consumers. CONCLUSIONS: More
      frequent among young women detainees, overall PAS consumption was quite close to
      that of male entrants, was greater than in the general female population, and was
      very often accompanied by psychological distress. Effective screening upon entry
      into detention should be carried out so that female consumers can be offered
      psychological and/or psychiatric care adapted to a prison environment.

PMID- 22981310
TI  - Oropharyngeal dysphagia in Parkinson's disease: comments on paper by Kalf et al.

PMID- 22981311
TI  - Independent validation of the non motor symptoms scale for Parkinson's disease in
      Brazilian patients.
AB  - OBJECTIVE: Independent validation of the Non motor Symptoms Scale in Parkinson's
      disease (NMSS) based on a cross-culturally adapted Brazilian version. METHODS:
      Parkinson's disease (PD) patients were evaluated by means of the Scales for
      Outcomes in Parkinson's disease-Motor (SCOPA-M), Autonomic, Cognition, and
      Psychosis; Hoehn and Yahr staging (H&Y); Berg Balance Scale; PD Sleep Scale;
      Clinical Impression of Severity Index for PD (CISI-PD); PDQ-39; and EQ-5D. The
      following clinimetric attributes were explored for the NMSS: acceptability,
      scaling assumptions, reliability, construct validity, and precision. RESULTS: 150
      patients were assessed (mean age 63.1 years; 56.7% males; mean duration of
      illness 8.7 years; HY median: 2). Mean NMSS was 48.9 (SD 36.3; median 42;
      skewness 1.3). Neither floor nor ceiling effect was observed on the NMSS total
      score. For domains, the Cronbach's alpha coefficient ranged from 0.40 to 0.82.
      The NMSS total score correlated significantly with SCOPA-AUT (r(S) = 0.65) and
      with those scales measuring related constructs (r(S) = 0.46-0.57). NMSS
      significantly increased as the H&Y stage increased (Kruskal-Wallis, p < 0.0001).
      These values were quite close to those from the original validation studies.
      CONCLUSIONS: The NMSS is a reliable and valid measure to evaluate non motor
      symptoms in Brazilian PD patients.

PMID- 22981312
TI  - Prepro-thyrotropin releasing hormone expressing neurons in the
      juxtaparaventricular region of the lateral hypothalamus are activated by leptin
      and altered by prenatal glucocorticoid exposure.
AB  - The neuropeptide thyrotropin-releasing hormone (TRH) is recognized to play an
      important role in controlling energy balance through direct effects on the CNS,
      although mechanisms explaining the phenomenon are poorly understood. To begin to
      understand the effects of TRH on CNS control of energy balance, we first mapped
      neurons expressing the TRH precursor peptide, prepro-TRH (ppTRH) in the
      paraventricular nucleus of the rat hypothalamus and the surrounding regions. We
      identified a population of ppTRH-expressing neurons in the juxtaparaventricular
      region of the lateral hypothalamus (LHAjp) which were stimulated by the satiety
      signal leptin (2.5MUg/kg, IP). Using a model of fetal glucocorticoid (GC)
      exposure in which pregnant rats were treated with the synthetic GC dexamethasone
      (DEX) during gestational days 18-21, it was observed that such exposure resulted
      in reduced numbers of ppTRH-ir neurons in the LHAjp in adult male and female
      rats, and was accompanied by increased food intake. Our data provide further
      insight into the biological role of the LHAjp, as well as the potential
      involvement of TRH neurons within this region in metabolic disease associated
      with fetal glucocorticoid exposure.

PMID- 22981314
TI  - Improving multi-tasking ability through action videogames.
AB  - The present study examined whether action videogames can improve multi-tasking in
      high workload environments. Two groups with no action videogame experience were
      pre-tested using the Multi-Attribute Task Battery (MATB). It consists of two
      primary tasks; tracking and fuel management, and two secondary tasks; systems
      monitoring and communication. One group served as a control group, while a second
      played action videogames a minimum of 5 h a week for 10 weeks. Both groups
      returned for a post-assessment on the MATB. We found the videogame treatment
      enhanced performance on secondary tasks, without interfering with the primary
      tasks. Our results demonstrate action videogames can increase people's ability to
      take on additional tasks by increasing attentional capacity.

PMID- 22981315
TI  - Use of inducible Atg5 deletion and expression cell lines in study of the pro
      survival function of autophagy under starvation.
AB  - At present the role of autophagy in cell death and cell survival remains
      controversial, partly owning to the contradictory results from the immortalized
      mouse embryonic fibroblasts (MEFs) with knockout of different autophagy-related
      genes (Atg). Here we aimed to reexamine the role of autophagy in cell death under
      starvation and other stress conditions. First, different clones of Atg5 knockout
      MEFs had different susceptibility to stress-mediated cell death, indicating that
      it is the clonal variation, rather than the deficiency of Atg5 or autophagy per
      se that determines the susceptibility. Next, we tested two cell lines with
      inducible Atg5 deletion or expression and demonstrated that cells without Atg5
      expression were more sensitive to starvation-induced apoptosis. Finally, we found
      that chloroquine was only effective in sensitizing starvation-induced cell death
      in Atg5-expressing cells, but not in Atg5-deficient cells. Such observations thus
      provide unequivocal evidence supporting the pro-survival function of autophagy
      under starvation. Moreover, our data demonstrate the usefulness of cells with
      inducible deletion or expression of Atg in the study of autophagy in cell death
      and cell survival.

PMID- 22981313
TI  - Might different cytokine trends in depressed patients receiving duloxetine
      indicate differential biological backgrounds.
AB  - BACKGROUND: Correlational studies investigating neurohormonal-cytokine modulation
      by antidepressants suggest, among others, variations in cytokines balances as
      state markers of different biological subtypes of major depressive disorder (MDD)
      and response predictors to specific treatments. Objective of the study was to
      investigate cytokines modulation by duloxetine, a relatively newer SNRI with
      "clean" dual serotonin/norepinephrine mechanism. METHODS: 30 MDD patients and 32
      healthy controls were assessed using Hamilton Depression Scale (HAM-D) and
      monitored for levels of IL-1beta, IL-2, IL-4, IL-10, IL-12, IFN-gamma and TNF
      alpha, at baseline, week 6 and week 12 of duloxetine treatment (60mg/day) and at
      baseline, respectively. RESULTS: Early responders (ER: defined at week 6 by
      reduction >50% of baseline HAM-D score) and early non-responders (ENR) showed
      opposite trends in cytokine levels during duloxetine treatment: ENR were
      characterized by baseline Th2 shift compared to controls (lower IL-1beta, IFN
      gamma and TNF-alpha) with increase in Th1 cytokines levels during treatment
      (increase of IL-1beta, IL-12, IFN-gamma, IL-1beta/IL-10 and TNF-alpha/IL-10,
      decrease of IL-10), achieving clinical response at week 12; ER were characterized
      by baseline Th2-to-Th1 relative switch compared to ENR (higher IL-1beta, IL
      1beta/IL-10 and TNF-alpha/IL-10) with reduction in Th1 cytokines levels during
      treatment (decrease of TNF-alpha and TNF-alpha/IL-10), achieving clinical
      response at week 6. LIMITATIONS: Small sample size. CONCLUSIONS: In accordance to
      early clinical response, duloxetine treatment could divide depressed patients
      into at least 2 subgroups characterized by clinical and laboratory differentiated
      behavior, suggesting different neurobiological background within depressive
      syndrome differentially sensitive to different drug components: pro-serotonergic
      effect and increase in Th1 cytokines in ENR vs. pro-noradrenergic effect and
      decrease in Th1 cytokines in ER.

PMID- 22981316
TI  - Identification of lipohemarthrosis with point-of-care emergency ultrasonography:
      case report and brief literature review.
AB  - BACKGROUND: Traumatic knee pain is a common complaint in the emergency department
      (ED). Conventional radiographs are often ordered as the initial screening study,
      but might not be readily available or always identify significant fractures.
      Ultrasonography has been shown to be useful in the evaluation of knee fractures
      not identified by radiography. OBJECTIVES: To discuss and briefly review the
      literature regarding the use of suprapatellar bursal ultrasonography to detect
      lipohemarthrosis (LH) as a surrogate marker for an intraarticular knee fracture.
      CASE REPORT: A 37-year-old man presented to the ED after a traumatic knee injury.
      Bedside ultrasonography demonstrated the characteristic triple layer sign of LH,
      raising the suspicion for an intraarticular fracture. The diagnosis was later
      confirmed with radiography and computed tomography (CT). CONCLUSIONS: The
      sonographic finding of LH may be used as a sensitive surrogate marker for
      intraarticular knee fracture in the ED. Ultrasound can be considered as an
      adjunct modality in ED patients with suspicion for fracture and negative knee
      radiographs.

PMID- 22981317
TI  - New MRI grading system for the diagnosis and management of mycetoma.
AB  - The management of patients with mycetoma depends on accurate identification of
      the causative organisms and of the extent of disease involvement along the
      different tissue planes. Disease involvement cannot accurately be assessed with
      the available diagnostic tools, so in this study we set out to evaluate the
      effectiveness of MRI in the diagnosis and management of mycetoma. Forty-two
      patients with confirmed mycetoma had MRI examination of the affected parts. A
      grading system, The Mycetoma Skin, Muscle, Bone Grading System (MSMBS), was used
      to describe and grade disease severity on the basis of MRI findings. The logistic
      regression test was used to correlate the clinical and MRI findings. The study
      showed that MRI can help in the diagnosis and management of mycetoma patients.
      The dot-in-circle sign, conglomerated foci with low signal intensity and macro-
      and micro-abscesses on a background of a hypointense matrix are all diagnostic of
      mycetoma. In patients with mycetoma, the MSMBS can grade disease severity,
      compare patients and help to manage them. Further studies are needed to determine
      to what extent the grading system can be used to determine a patient's prognosis.

PMID- 22981318
TI  - Strange-face illusions during inter-subjective gazing.
AB  - In normal observers, gazing at one's own face in the mirror for a few minutes, at
      a low illumination level, triggers the perception of strange faces, a new visual
      illusion that has been named 'strange-face in the mirror'. Individuals see huge
      distortions of their own faces, but they often see monstrous beings, archetypal
      faces, faces of relatives and deceased, and animals. In the experiment described
      here, strange-face illusions were perceived when two individuals, in a dimly lit
      room, gazed at each other in the face. Inter-subjective gazing compared to mirror
      gazing produced a higher number of different strange-faces. Inter-subjective
      strange-face illusions were always dissociative of the subject's self and
      supported moderate feeling of their reality, indicating a temporary lost of self
      agency. Unconscious synchronization of event-related responses to illusions was
      found between members in some pairs. Synchrony of illusions may indicate that
      unconscious response-coordination is caused by the illusion-conjunction of
      crossed dissociative strange-faces, which are perceived as projections into each
      other's visual face of reciprocal embodied representations within the pair. Inter
      subjective strange-face illusions may be explained by the subject's embodied
      representations (somaesthetic, kinaesthetic and motor facial pattern) and the
      other's visual face binding. Unconscious facial mimicry may promote inter
      subjective illusion-conjunction, then unconscious joint-action and response
      coordination.

PMID- 22981319
TI  - Infertility patients' knowledge of the effects of obesity on reproductive health
      outcomes.
AB  - OBJECTIVE: The objective of the study was to assess the infertility patient
      knowledge of reproductive outcomes affected by obesity. STUDY DESIGN: This was a
      prospective survey study of 150 female infertility patients in an academic
      medical center. Subjects were administered the Rapid Estimate of Adult Literacy
      in Medicine-Short Form and a questionnaire on the health risks of obesity, and
      investigators obtained height and weight measurements. RESULTS: Subjects' age
      ranged from 21 to 45 years (mean 34.8 +/- 4.94 SD) and body mass index ranged
      from 17.9 to 62.9 kg/m(2) (mean 26.5 +/- 7.54 SD). The following percentages of
      women were aware that obesity increases the risk of infertility (82.7%),
      irregular periods (70.0%), miscarriage (60.7%), cesarean section (48.7%), breast
      cancer (38.7%), birth defects (29.3%), stillbirth (22.7%), and endometrial cancer
      (20.7%). CONCLUSION: Among women with infertility, there is limited knowledge of
      reproductive outcomes affected by obesity. Public education is needed to increase
      awareness. Women undergoing fertility treatment are motivated for reproductive
      success and may be uniquely receptive to obesity education and weight loss
      intervention.

PMID- 22981320
TI  - Longitudinal evaluation of predictive value for preeclampsia of circulating
      angiogenic factors through pregnancy.
AB  - OBJECTIVE: The purpose of this study was to examine whether longitudinally
      sampled maternal angiogenic concentrations predict preeclampsia. STUDY DESIGN:
      Plasma sFlt-1 and placental growth factor (PlGF) concentrations in healthy
      pregnant women were quantified at 10, 17, 25, and 35 weeks' gestation.
      Preeclampsia was diagnosed with criteria from the American College of
      Obstetricians and Gynecologists. RESULTS: In the first trimester,
      sensitivity/specificity for PlGF and sFlt-1 were 55/43% and 57/40%, respectively,
      and did not improve appreciably as the pregnancy progressed. Among pregnancies
      that later experienced preeclampsia, median PlGF was lower beginning in the
      second trimester, but sFlt-1 was not higher until the third trimester. Analyte
      positive predictive values approached 10% in the third trimester. Negative
      predictive values were >90% for the entire pregnancy. CONCLUSION: Prediction of
      preeclampsia in early pregnancy was not possible with the use of maternal
      angiogenic protein concentrations. Even in late pregnancy, positive predictive
      values were not useful clinically. Negative predictive values are similarly
      unlikely to prove useful as a tool with which to a rule out suspected disease.

PMID- 22981321
TI  - The effect of human antibacterial peptide LL-37 in the pathogenesis of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Previous research has shown that innate immune system was more
      important than the acquired immune system in the pathogenesis of COPD. LL-37 is
      the only human cathelicidin identified so far. As an integral part of the innate
      immune system, besides antibacterial activity, its chemotactic activity, damage
      repairing, influencing apoptosis and its cytotoxicity are attracting people's
      attention. The aim of the present study was to evaluate role of LL-37 in the
      pathogenesis of COPD. METHODS: ELISA and immunohistochemistry were applied to
      investigate the expression of LL-37 in induced sputum and lung tissue of COPD
      patients. Bronchial epithelial cell (BEP2D) and alveolar epithelial cell (A549)
      were treated with LL-37 synthesis polypeptide in vitro to assess the role of LL
      37 in inflammation and apoptosis. RESULTS: We found that increased induced sputum
      levels of LL-37 in COPD patients were associated with airflow limitation, health
      status and exercise tolerance and the expressing intensity of LL-37 in both
      airway district and pulmonary alveoli area in COPD group significantly increased
      compared with control group. Through stimulation by CSE and LPS, the expression
      of LL-37 was increased in bronchial epithelial cell and alveolar epithelial cell.
      LL-37 synthesis polypeptide can promote the releasing of inflammatory factor IL-8
      and induce apoptosis of bronchial epithelial cell and alveolar epithelial cell.
      CONCLUSION: This study suggested that LL-37 may play important role in the
      pathogenesis of COPD and may be a possible novel therapeutic target in COPD.

PMID- 22981322
TI  - Outcomes in elderly Danish citizens admitted with community-acquired pneumonia.
      Regional differencties, in a public healthcare system.
AB  - OBJECTIVES: To evaluate regional differences in and risk factors for admission,
      length of stay, mortality, and readmission for community-acquired pneumonia in
      elderly Danish patients. METHODS: National registry study on elderly Danish
      citizens with an acute admission in 2009 owing to community-acquired pneumonia.
      We studied differences among hospitals in length of stay, in-hospital mortality,
      mortality within 30 days of discharge, and readmission within 30 days after
      discharge using Cox regression models with adjustments for age, sex, ventilatory
      support, and co-morbidity by Charlson's index score. RESULTS: A total of 11,332
      elderly citizens were admitted with community-acquired pneumonia. Mortality
      during admission and 30-days from discharge were 11.6% and 16.2%, respectively.
      Readmission rates within 30 days of discharge were 12.3%. There were
      significantly differences between hospitals in length of stay. A high Charlson
      index score and advanced age were significantly risk factors for death during
      admission and within 30 days of discharge. Male sex and high Charlson index score
      were significant risk factors for readmission. Admission to large bed capacity
      hospital was a significant risk factor for death and readmission within 30 days
      of discharge. CONCLUSIONS: Length of stay, rate of admission, mortality and
      readmission in elderly Danish patients with community-acquired pneumonia follows
      international findings. There are regional differences between hospitals. In
      depth investigation in regional differences could reveal potential feasible
      clinical interventions with an improvement of readmission-, mortality rates and
      cost.

PMID- 22981323
TI  - [Cardiovascular risk and human immunodeficiency virus infection].

PMID- 22981324
TI  - [Incomplete Kawasaki disease concomitant with influenza A H1N1 virus and
      rotavirus coinfection].

PMID- 22981325
TI  - [Unusual cestodiasis in a Spanish infant].

PMID- 22981326
TI  - [Pythium insidiosum ocular infection].

PMID- 22981327
TI  - Comparison of an intermittent and continuous forearm muscles fatigue protocol
      with motorcycle riders and control group.
AB  - Motorcycle races' long duration justify the study of forearm muscles fatigue,
      especially knowing the frequently associated forearm discomfort pathology.
      Moreover, while continuous fatigue protocols yield unequivocal results, EMG
      outcomes from an intermittent protocol are quite controversial. This study
      examined the forearm muscle fatigue patterns produced during these two protocols,
      comparing riders with a control group, and relating maximal voluntary contraction
      with EMG parameters (amplitude - NRMS and median frequency - NMF) of both
      protocols to the forearm discomfort among motorcycle riders. Twenty riders and 39
      controls performed in separate days both protocols simulating the braking gesture
      and posture of a rider. EMG of flexor digitorum superficialis (FS) and carpi
      radialis (CR) were monitored. CR revealed more differences among protocols and
      groups compared to FS. The greater CR activation in riders could be interpreted
      as a neuromotor strategy to improve braking precision. When FS fatigue increased,
      the control group progressively shift toward a bigger CR activation, adopting an
      intermuscular activation pattern closer to riders. Despite the absence of NMF
      decrement throughout the intermittent protocol, which suggest that we should have
      shorten the recovery times from the actual 1 min, the superior number of rounds
      performed by the riders proved that this protocol discriminates better riders
      against controls and is more related to forearm discomfort.

PMID- 22981328
TI  - Synthesis, characterization and biological evaluation of some novel 2,4
      thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic
      agents.
AB  - A series of some novel 2,4-thiazolidinediones (TZDs) (2a-x) have been synthesized
      and characterized by FTIR, (1)H NMR, (13)C NMR and LC mass spectral analysis. All
      the synthesized compounds were evaluated for their cytotoxicity, antimicrobial
      and in vivo antihyperglycemic activities. Among the tested compounds for
      cytotoxicity using Brine Shrimp Lethality assay, compound 2t ((Z)-5-(4-((E)-3-oxo
      3-(thiophen-2-yl)prop-1-enyl)benzylidene)-1,3-thiazolidine-2,4-dione) exhibited
      significant inhibitory activity at ED(50) value 4.00+/-0.25 MUg/mL and this level
      of activity was comparable to that of the reference drug podophyllotoxin with
      ED(50) value 3.61+/-0.17 MUg/mL. Antimicrobial activity was screened using agar
      well diffusion assay method against selected Gram-positive, Gram-negative and
      fungal strains and the activity expressed as the minimum inhibitory concentration
      (MIC) in MUg/mL. From the results of antimicrobial activity compound 2s ((Z)-5-(4
      ((E)-3-(3,5-bis(benzyloxy)phenyl)-3-oxoprop-1-enyl)benzylidene)-1,3-thiazolidine
      2,4-dione) was found to be the most active against all the tested strains of
      microorganisms with MIC value 16 MUg/mL. In vivo antihyperglycemic effect of
      twenty four TZDs (2a-x) at different doses 10, 30 and 50mg/kg b.w (oral) were
      assessed using percentage reduction of plasma glucose (PG) levels in
      streptozotocin-induced type II diabetic rat models. From the results, the novel
      compound 2x ((Z)-5-(4-((E)-3-(9H-fluoren-2-yl)-3-oxoprop-1-enyl)benzylidene)-1,3
      thiazolidine-2,4-dione) exhibited considerably potent blood glucose lowering
      activity than that of the standard drug rosiglitazone and it could be a
      remarkable starting point to evaluate structure-activity relationships and to
      develop new lead molecules with potential cytotoxicity, antimicrobial and
      antihyperglycemic activities. In addition molecular docking studies were carried
      out against PPARgamma molecular target using Molegro Virtual Docker v 4.0 to
      accomplish preliminary confirmation of the observed in vivo antihyperglycemic
      activity.

PMID- 22981329
TI  - Synthesis and pharmacological evaluation of a novel series of 3-aryl-2-(2
      substituted-4-methylthiazole-5-yl)thiazolidin-4-one as possible anti-inflammatory
      and antimicrobial agents.
AB  - A new series of 3-aryl-2-(2-aryl/benzyl-4-methylthiazole-5-yl)thiazolidin-4-one
      was synthesized by condensation of 2-aryl/benzyl-4-methylthiazole-5-carbaldehyde,
      aromatic amines and thioglycolic acid in toluene. All the synthesized compounds
      are characterized by IR, NMR and elemental or mass analysis. Sixteen out of the
      newly synthesized compounds were screened for in vivo anti-inflammatory activity
      using carrageenan-induced rat paw edema method. Some of the synthesized compounds
      exhibited good anti-inflammatory activity compared with indomethacin. The
      synthesized compounds were also evaluated for their in vitro antimicrobial
      activity. Some of the compounds showed mild antibacterial activity while most of
      the compounds showed good antifungal activity.

PMID- 22981330
TI  - Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4
      disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry.
AB  - We have synthesized and evaluated a series of 1,4-disubstituted-triazole
      derivatives for inhibition of the rat Na(V)1.6 sodium channel isoform, an isoform
      thought to play an important role in controlling neuronal firing. Starting from a
      series of 2,4(1H)-diarylimidazoles previously published, we decided to extend the
      SAR study by replacing the imidazole with a different heterocyclic scaffold and
      by varying the aryl substituents on the central aromatic ring. The 1,4
      disubstituted 1,2,3-triazoles were prepared employing the copper-catalyzed azide
      alkyne cycloaddition (CuAAC). Many of the new molecules were able to block the
      rNa(v)1.6 currents at 10 MUM by over 20%, displaying IC(50) values ranging in the
      low micromolar, thus indicating that triazole can efficiently replace the central
      heterocyclic core. Moreover, the introduction of a long chain at C4 of the
      central triazole seems beneficial for increased rNa(v)1.6 current block, whereas
      the length of N1 substituent seems less crucial for inhibition, as long as a
      phenyl ring is not direcly connected to the triazole. These results provide
      additional information on the structural features necessary for block of the
      voltage-gated sodium channels. These new data will be exploited in the
      preparation of new compounds and could result in potentially useful AEDs.

PMID- 22981331
TI  - Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid
      hybrids as multi-targeted compounds against Alzheimer's disease.
AB  - A novel series of tacrine-caffeic acid hybrids (5a-f) were designed and
      synthesized by combining caffeic acid (CA) with tacrine. The antioxidant study
      revealed that all the hybrids have much more antioxidant capacities compared to
      CA. Among these compounds, 5e showed the highest selectivity in inhibiting
      acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Enzyme kinetic
      study had suggested that 5e binds to both catalytic (CAS) and peripheral anionic
      sites (PAS) of AChE. Moreover, compound 5e also inhibited self- or AChE-induced
      beta-amyloid(1-40) aggregation, as well as had potent neuroprotective effects
      against H(2)O(2)- and glutamate- induced cell death with low toxicity in HT22
      cells.

PMID- 22981332
TI  - Optimization of an ether series of mGlu5 positive allosteric modulators:
      molecular determinants of MPEP-site interaction crossover.
AB  - We report the optimization of a series of non-MPEP site metabotropic glutamate
      receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) based on a simple
      acyclic ether series. Modifications led to a gain of MPEP site interaction
      through incorporation of a chiral amide in conjunction with a nicotinamide core.
      A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent
      model of psychosis. These studies suggest that potent PAMs within topologically
      similar chemotypes can be developed to preferentially interact or not interact
      with the MPEP allosteric binding site.

PMID- 22981333
TI  - Preparation and optimization of new 4-(morpholin-4-yl)-(6-oxo-1,6
      dihydropyrimidin-2-yl)amide derivatives as PI3Kbeta inhibitors.
AB  - From a HTS campaign, a new series of pyrimidone anilides exemplified by compound
      1 has been identified with good inhibitory activity for the PI3Kbeta isoform. The
      structure of compound 1 in PI3Kgamma was solved revealing a binding mode in
      agreement with the SAR observed on PI3Kbeta. These compounds displayed inhibition
      in the nanomolar range in the biochemical assay and were also potent p-Akt
      inhibitors in a PTEN-deficient PC3 prostate cancer cell line. Optimization of in
      vitro pharmocokinetic properties led to compound 25 exhibiting 52%
      bioavailability in mice and target engagement in an acute PK/PD study.

PMID- 22981334
TI  - Synthesis and biological evaluation of novel piperazine derivatives of flavone as
      potent anti-inflammatory and antimicrobial agent.
AB  - A series of novel 6-methoxy-2-(piperazin-1-yl)-4H-chromen-4-one and 5,7-dimethoxy
      2-(piperazin-1-ylmethyl)-4H-chromen-4-one derivatives of biological interest were
      prepared and screened for their pro-inflammatory cytokines (TNF-alpha and IL-6)
      and antimicrobial activity (antibacterial and antifungal). Among all the compound
      screened (5a-j and 10k-t), the compounds 5c, 5g, 5h, 10l, 10m, 10n and 10r found
      to have promising anti-inflammatory activity (up to 65-87% TNF-alpha and 70-93%
      IL-6 inhibitory activity) at concentration of 10 MUM with reference to standard
      dexamethasone (71% TNF-a and 84% IL-6 inhibitory activities at 1 MUM) while the
      compounds 5b, 5i, 5j, 10s and 10t found to be potent antimicrobial agent showing
      even 2 to 2.5-fold more potency than that of standard ciprofloxacin and
      miconazole at the same MIC value of 10 MUg/mL.

PMID- 22981335
TI  - Pyrrolo[2,3-b]quinoxalines as inhibitors of firefly luciferase: their Cu-mediated
      synthesis and evaluation as false positives in a reporter gene assay.
AB  - 2-Substituted pyrrolo[2,3-b]quinoxalines having free NH were prepared directly
      from 3-alkynyl-2-chloroquinoxalines in a single pot by using readily available
      and inexpensive methane sulfonamide (or p-toluene sulfonamide) as an ammonia
      surrogate. The reaction proceeded in the presence of Cu(OAc)(2) affording the
      desired product in moderate yield. The crystal structure analysis of a
      representative compound and its supramolecular interactions are presented. Some
      of the compounds synthesized exhibited inhibitory activities against luciferase
      that was supported by the predictive binding mode of these compounds with
      luciferase enzyme through molecular docking studies. The key observations
      disclosed here can alert users of luciferase reporter gene assays for possible
      false positive results due to the direct inhibition of luciferase.

PMID- 22981336
TI  - Effects of the patient's age and the size of the primary lesion on the speed of
      shrinkage after marsupialisation of keratocystic odontogenic tumours, dentigerous
      cysts, and radicular cysts.
AB  - Marsupialisation, by which a surgical window is created in the cavity of a cystic
      lesion, has been recommended to avoid the formation of a bony defect in the jaw
      and a reduction in a patient's quality of life. However, information about the
      factors that affect the reduction in the size of a cyst after marsupialisation is
      limited. We have studied the effects of the patient's age and the size of the
      primary lesion on the speed of shrinkage after marsupialisation of keratocystic
      odontogenic tumours (KCOTs), dentigerous cysts, and radicular cysts. The speed of
      shrinkage (mm(2)/month) was evaluated by measuring the radiolucent area on
      panoramic radiographs taken before and after marsupialisation for KCOT (n=28),
      dentigerous cysts (n=26), and radicular cysts (n=18) in the mandibular molar
      regions. The mean duration of marsupialisation for each type of cyst was 11 (5),
      8 (5), and 5 (2) months, respectively. The radiolucent area decreased linearly in
      the 3 types depending on the time after marsupialisation: r=-0.86 (p<0.01), r=
      0.73 (p<0.01), and r=-0.72 (p<0.01), respectively. The relative speed of
      shrinkage did not correlate with the age of the patients, though it did correlate
      with the size of the radiolucent area before marsupialisation in KCOT (r=0.69,
      p<0.01) and radicular cysts (r=0.73, p<0.01). These results suggest that the size
      of a cyst before marsupialisation may affect the speed of shrinkage in KCOT and
      radicular cysts, while the age of the patient does not.

PMID- 22981337
TI  - Epidemiology of epilepsy in New Valley Governorate, Al Kharga District, Egypt.
AB  - Epilepsy is one of the serious neurological disorders which results in profound
      morbidity and mortality. Although epilepsy has no geographical boundaries,
      understanding cultural, social, and economic backgrounds is a very important step
      for interpretation of its epidemiological characteristics. This work aims to
      study the epidemiological profile of epilepsy in New Valley Governorate and to
      estimate its magnitude of treatment gap. It was conducted in a door to door
      survey, including all inhabitants (62,583 subjects), by 3 neurologists to detect
      any suspected case of focal or generalized epilepsy. All suspected cases were
      subjected to detailed history, clinical examination, EEG, neuroimaging studies,
      and estimation of serum drug level if needed. The study revealed that life time
      prevalence of epilepsy in Al Kharga district is 6.76/1000, with highest peak
      during early child hood, while that of active epilepsy is 4.99/1000 population.
      The annual incidence rate is 43.14/100,000, and age specific incidence rate has a
      U-shaped pattern with two peaks of incidence at early infancy and elderly.
      Localization-related epilepsy is the most frequently encountered type (53.7%).
      However the treatment gap of epilepsy in New Valley is similar to that in
      developing countries (61.5%). CONCLUSION: Prevalence and Incidence Rate of
      epilepsy in New Valley are similar to that in industrialized countries.

PMID- 22981338
TI  - Bioavailability of intranasal vs. rectal diazepam.
AB  - There remains an unmet medical need in the out-of-hospital management of seizure
      emergencies because older children and adults often refuse treatment with
      diazepam rectal gel due to social objections. We have previously reported that
      intranasal diazepam (DZP) administration is feasible, with maximum plasma
      concentrations (C(max)) and time to maximum concentration (T(max)) that are
      comparable to rectal DZP; but tolerability was poor. In the present study, the
      tolerability and pharmacokinetics of two investigational nasal formulations were
      compared with DZP rectal gel. Twelve healthy volunteers were enrolled into an
      active-control, double-blind, four-period, crossover pharmacokinetic and
      tolerability study. Three intranasal treatments (Nas-A 10mg, Nas-B 10mg and Nas-B
      13.4 mg) were compared to a 10mg dose of the rectal gel. A single dose of each
      formulation was administered followed by at least a 14 day washout period. Blood
      samples for plasma DZP concentration-time characterization were collected pre
      dose and at regular intervals to 240 h post-dose. Tolerability and sedation were
      assessed using visual analog scales. Mean DZP C(max) (+/-SD) was 181.8 +/- 84.16,
      151.3 +/- 108.1 and 180.7 +/- 82.1 ng/mL for Nas-A 10mg, Nas-B 10 and Nas-B 13.4
      mg respectively; in comparison the C(max) for the rectal gel was 160.9 +/- 109.4
      ng/mL. Median T(max) was 0.75 h for all treatments. Both intranasal formulations
      were well tolerated and exhibited relatively rapid, but variable, absorption with
      bioavailability of 70-90% relative to DZP rectal gel. This study shows that the
      development of a well-tolerated nasal formulation is possible and that the rate
      and extent of absorption approximates that of DZP rectal gel. We conclude that
      intranasal DZP offers a viable alternative to rectal administration, but
      enhancement of formulations is needed to improve the extent and consistency of
      absorption.

PMID- 22981339
TI  - Epilepsy and driving: current status of research.
AB  - In many parts of the world, licensing guidelines state that drivers with medical
      conditions such as epilepsy are restricted or prohibited from driving. These
      guidelines are sometimes subjective and not strongly evidence-based, rendering
      the task of assessing fitness to drive a complex one. Determining fitness to
      drive is not only essential for maintaining the safety of individual drivers but
      has implications for the community at large. It is therefore important to review
      the current state of knowledge regarding epilepsy and driving in order to aid
      health professionals required to assess fitness to drive and to guide future
      research directions. This review outlines the functional impairments related to
      epilepsy and driving, treatment and management issues, motor vehicle crash risk
      for drivers with epilepsy, estimates of predicted seizure occurrence and
      concludes with a discussion of the international licensing guidelines and
      relevant legal issues. More comprehensive research, including investigation into
      the effects of antiepileptic medication on driving, could aid in the development
      of policies and guidelines for assessing fitness to drive.

PMID- 22981340
TI  - Age at menarche, menstrual patterns, and menstrual characteristics in Jordanian
      adolescent girls.
AB  - OBJECTIVE: To estimate the distribution of age at menarche and investigate
      menstrual patterns and symptoms among adolescent Jordanian girls. METHODS:
      Menstrual status data were collected from 596 secondary-school students from the
      Amman area via a self-administered questionnaire. Descriptive statistics, cross
      tabulation, and correlation coefficient calculations were used where appropriate,
      and probit analysis was applied to estimate mean +/- SD age at menarche. RESULTS:
      The students' mean age was 15.7 +/- 1.5 years. Mean age at menarche was 13.1 +/-
      1.1 years for those who recalled it and 12.8 +/- 1.4 years per the probit
      analysis. Menstruation duration was 4 to 7 days for 73.6% of the students, and it
      was more than 7 days for 2.2%. Mid-cycle pain was reported by 30.9% and
      dysmenorrhea by 37.6% of the students, 8% of whom needed to miss school 1 day per
      cycle. Body mass index was correlated with age at menarche (P=0.002). CONCLUSION:
      The mean age at menarche was close to that reported in studies from Europe and
      the USA, but it was younger than the age reported in studies from Africa.

PMID- 22981341
TI  - Novel mithramycins abrogate the involvement of protein factors in the
      transcription of cell cycle control genes.
AB  - The effects of mithramycin SK (MSK) and demycarosyl-3D-beta-D-digitoxosyl
      mithramycin SK (DIG-MSK; EC-8042), two novel analogs of the antitumor antibiotic
      mithramycin A, on gene transcription were examined in human HCT116 colon
      carcinoma cells by quantitative real-time PCR of 89 genes mainly involved in cell
      cycle control. Each one of the analogs down-regulated a different set of genes,
      while only five genes were down-regulated by both compounds. Moreover, other
      genes were significantly up-regulated, among them p21(WAF1)/CDKN1A which is
      involved in halting cells at the G1 and G2/M checkpoints. These results are
      rationalized in terms of MSK or DIG-MSK competition with various transcription
      factors for binding to consensus C/G-rich tracts encompassed in gene promoters.
      Changes in cell cycle distribution and protein levels after treatment with every
      analog were consistent with changes observed in gene expression.

PMID- 22981342
TI  - The role of postoperative prophylactic antibiotics in the treatment of facial
      fractures: a randomised, double-blind, placebo-controlled pilot clinical study.
      Part 1: orbital fractures in 62 patients.
AB  - The aim of this study was to evaluate the difference between the effects of a 5
      day and a 1-day course of antibiotics on the incidence of postoperative infection
      after displaced fractures of the orbit. A total of 62 patients with orbital blow
      out fractures were randomly assigned to two groups, both of which were given
      amoxicillin/clavulanic acid 1.2g intravenously every 8h from the time of
      admission to 24h postoperatively. The 5-day group were then given
      amoxicillin/clavulanic acid 625 mg orally every 8h for 4 further days. The 1-day
      group were given placebo orally at the same time intervals. Follow up
      appointments were 1, 2, 4, 6, and 12 weeks, and 6 months, postoperatively. An
      infection in the orbital region was the primary end point. Sixty of the 62
      patients completed the study. Two of the 29 patients in the 5-day group (6.8%)
      and 1/31 patients in the 1-day group (3.2%) developed local infections. In the 5
      day group 1 patient developed diarrhoea. In the 1-day group 1 patient developed a
      rash on the trunk. There were no significant differences in the incidence of
      infection or side effects between the groups. We conclude that in displaced
      orbital fractures a postoperative 1-day course of antibiotics is as effective in
      preventing infective complications as a 5-day regimen.

PMID- 22981343
TI  - Finite element analysis of three patterns of internal fixation of fractures of
      the mandibular condyle.
AB  - The most stable pattern of internal fixation for fractures of the mandibular
      condyle is a matter for ongoing discussion. In this study we investigated the
      stability of three commonly used patterns of plate fixation, and constructed
      finite element models of a simulated mandibular condylar fracture. The completed
      models were heterogeneous in the distribution of bony material properties,
      contained about 1.2 million elements, and incorporated simulated jaw-adducting
      musculature. Models were run assuming linear elasticity and isotropic material
      properties for bone. This model was considerably larger and more complex than
      previous finite element models that have been used to analyse the biomechanical
      behaviour of differing plating techniques. The use of two parallel 2.0 titanium
      miniplates gave a more stable configuration with lower mean element stresses and
      displacements over the use of a single miniplate. In addition, a parallel
      orientation of two miniplates resulted in lower stresses and displacements than
      did the use of two miniplates in an offset pattern. The use of two parallel
      titanium plates resulted in a superior biomechanical result as defined by mean
      element stresses and relative movement between the fractured fragments in these
      finite element models.

PMID- 22981344
TI  - The nature and scope of moonlighting by radiology trainees.
AB  - RATIONALE AND OBJECTIVES: The practice of moonlighting by trainees is a
      longstanding controversy; however, the resident point of view remains distinctly
      underrepresented in the radiology literature. We report the resident perspective
      on the moonlighting practices of radiology trainees. METHODS: Survey data were
      collected from resident members of the Association of University Radiologists
      representing 84 training programs in the United States to assess their routine
      and extracurricular clinical responsibilities. Descriptive statistics were used
      to analyze these data. RESULTS: Moonlighting is practiced by radiology trainees
      at nearly three-fourths of the programs represented in this survey. Interpreting
      diagnostic imaging (85.5%) and monitoring contrast administrations (72.6%) are
      the most common duties performed. Twenty-one percent of moonlighting trainees
      perform procedures (excluding diagnostic fluoroscopy) in their extracurricular
      positions; of these, most (61.5%) are without attending supervision. Most
      trainees that moonlight spend 1 to 10 hours weekly doing so while averaging a 59
      hour workweek at their primary jobs. CONCLUSIONS: The clinical duties of
      moonlighting trainees may be more diverse than has been previously recognized.
      Although major discrepancies between overnight radiology trainee interpretations
      and attending final interpretations have been shown to be infrequent, the
      consequences of trainees performing procedures and monitoring adverse contrast
      reactions without attending supervision are unknown. The financial and
      professional benefits of moonlighting must be weighed against the potential for
      harm. Our data suggest that most moonlighting radiology trainees operate within
      the Accreditation Council for Graduate Medical Education-mandated 80-hour weekly
      work limit; the mandatory 8-hour break between shifts and 24-hour continuous duty
      limit may pose logistical challenges.

PMID- 22981345
TI  - Origin and evolution of PIN auxin transporters in the green lineage.
AB  - Polarized auxin transport is crucial for many developmental processes in
      flowering plants and requires the PIN-FORMED (PIN) family of auxin efflux
      carriers. However, the impact of polar auxin transport and PIN proteins on the
      development of non-seed plant species and green algal lineages is largely
      unknown. Using recently available sequence information from streptophyte algae
      and other non-seed plant species, we have constructed a preliminary phylogenetic
      framework and present several hypotheses for PIN protein evolution. We postulate
      that PIN proteins originated in streptophyte algae at the endoplasmic reticulum
      (ER) and that plasma membrane localization was acquired during land plant
      evolution. We also suggest that PIN proteins are evolutionarily distinct from
      another family of auxin transporters at the ER, the PIN-LIKES (PILS) proteins.

PMID- 22981346
TI  - Simultaneous determination of eight corticosteroids in bovine tissues using
      liquid chromatography-tandem mass spectrometry.
AB  - This paper describes a newly developed method for the simultaneous determination
      of eight corticosteroid residues in bovine muscle, liver and kidney samples using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). The determination of
      methylprednisone, the main metabolite of methylprednisolone, in bovine tissues
      using LC-MS/MS is carried out for the first time. The method development
      demonstrates that the pH is important in optimizing the sample preparation. Tests
      performed using different solid-phase extraction (SPE) cartridges were enabled to
      produce conditions for reducing the matrix effects (ion suppression and
      enhancement) of analysis. Acidic condition and mixed-mode cation exchange SPE
      columns resulted in the most suitable clean-up for muscle and liver, and also
      yielded acceptable results for kidney. The enhanced sample clean-up resulted in
      excellent clear baselines of ion transitions, and therefore, a higher delta
      electron multiplier voltage (DeltaEMV) could be set in the MS/MS detector. The
      application of 500 V of DeltaEMV improved the signal responses, however, the
      noise level did not change, and consequently, the overall sensitivity and
      analytical limits (limit of detection, limit of quantification) could be
      enhanced. In the HPLC separation, the recently introduced Kinetex phenyl-hexyl
      core-shell type column was used that enabled baseline separation for
      dexamethasone and its beta-epimer, betamethasone. Dexamethasone and betamethasone
      were eluted within 12 min and such reduced retention, obtained with core-shell
      HPLC type column, further enhanced the sensitivity. The method was validated
      according to the European Union (EU) 2002/657/EC Decision; the studied parameters
      met the EU standards. The decision limits and limit of detections were calculated
      in each matrix for all corticosteroids and varied from 0.01 to 13.3MUg/kg and
      from 0.01 to 0. 1 MUg/kg, respectively.

PMID- 22981347
TI  - Whole-cell recording from Kenyon cells in silkmoths.
AB  - Kenyon cells (KCs), which are present in the mushroom bodies (MBs) of the insect
      brain, play an important role in olfactory information processing and associative
      learning. However, the intrinsic electrophysiological properties of KCs in
      silkmoth (Bombyx mori) MBs remain unknown. Here, we use whole-cell patch-clamp
      recordings to elucidate the functional parameters of membrane voltage and voltage
      activated ionic currents of KCs in silkmoth MBs. KCs generated action potentials
      in response to stepping pulses of depolarizing current, and application of GABA
      receptor blocker abolished inhibitory synaptic inputs and depolarized resting
      membrane potential. Pharmacological isolation of KC voltage-gated ionic currents
      revealed that KCs express a range of voltage-activated channels, including
      transient and non-inactivating potassium, sodium, and calcium channels. Our
      results provide the first electrophysiological characterization of KCs in
      silkmoth MBs and represent an important step toward understanding neuronal
      computation that underlies olfactory information processing in silkmoths.

PMID- 22981348
TI  - Development of a guideline on reading CT images of malignant pleural mesothelioma
      and selection of the reference CT films.
AB  - PURPOSE: International experts developed a guideline on reading CT images of
      malignant pleural mesothelioma for radiologists and physicians. It is intended
      that it act as a supplement to the current International Classification of HRCT
      for Occupational and Environmental Respiratory Diseases. METHODS: The research
      literatures on mesothelioma CT features were systematically reviewed. Ten
      mesothelioma CT features were adopted into the guideline prepared according to
      experts' opinion. The terminology of mesothelioma CT features and mesothelioma
      probability were agreed by consensus of experts. The CT reference films for each
      mesothelioma feature were selected based on agreement by experts from 22 definite
      mesothelioma cases confirmed pathologically and immunohistochemically. To support
      the validity of the mesothelioma probability, 4 experts' readings of CT films
      from 57 cases with or without mesothelioma were analyzed by kappa statistics
      between the experts; sensitivity and specificity for mesothelioma were also
      assessed. RESULTS: The mesothelioma CT Guideline was developed, providing the
      terminology of CT features and the mesothelioma probability, the judgement of
      severity, the distribution of mesothelioma, and the revised CT reading sheet
      including mesothelioma items. The CT reference films with ten mesothelioma
      typical features were selected. The average linearly and quadratically weighted
      kappa of the agreement on the 4-point scale mesothelioma probability were 0.58
      and 0.71, respectively. The average sensitivity and specificity for mesothelioma
      were 93.2% and 65.6%, respectively. CONCLUSION: The evidence-based mesothelioma
      CT Guideline developed may serve as a good educational tool to facilitate
      physicians in recognising mesothelioma and improve their proficiency in diagnosis
      of mesothelioma.

PMID- 22981349
TI  - Interleukin-15 is a major regulator of the cell-microenvironment interactions in
      human renal homeostasis.
AB  - Experiments in IL-15(-/-) and IL-15Ralpha(-/-) mice show that intra-renal IL-15,
      through IL-15Ralpha behaves as an epithelial survival factor. Recent data
      highlight new functions of IL-15 in renal homeostasis mediated by IL-15Rgamma
      (CD132). Indeed, in CD132+ renal epithelial tubular cells IL-15 preserves E
      cadherin expression inhibiting epithelial-mesenchymal transition (EMT). By
      contrast, during allograft rejection, the increased intra-graft IL-15 expression
      favors tubular destruction facilitating the intraepithelial recruitment of CD8 T
      cells expressing the E-cadherin ligand CD103. In renal cancer, loss of CD132 by
      epithelial cells defines a tumoral microenvironment where IL-15 triggers E
      cadherin down-regulation and EMT. Finally, in CD132+ renal cancer stem cells IL
      15 induces the generation of non-tumorigenic epithelial cells sensitive to
      cytotoxic drugs. These findings are discussed in the light of IL-15-based
      immunotherapy for renal cancer.

PMID- 22981350
TI  - Nuclear survivin expression is associated with a poor prognosis in Caucasian non
      small cell lung cancer patients.
AB  - BACKGROUND: The role of the nuclear protein survivin in non-small cell lung
      cancer (NSCLC) remains controversial. To clarify the association of survivin with
      survival in NSCLC, we performed a meta-analysis of the literature with meta
      analysis. METHODS: Trials were selected for further analysis if they provided an
      independent assessment of nuclear survivin in NSCLC and reported the survival
      data in the context of survivin status. A total of 7 trials, which comprised 823
      patients, were included in the meta-analysis. Sensitivity analyses were conducted
      using the patient's disease stage, IHC cutoff value, and ethnicity. RESULTS: The
      combined hazard ratio (HR) of 1.54 [95% CI, 0.79-3.02; test for heterogeneity
      p<0.001] suggests that high nuclear survivin expression has no impact on patient
      survival. However, when the studies were restricted to Caucasian patients, high
      levels of nuclear survivin expression were correlated with reduced survival (HR
      2.38, 95% CI=1.60-3.52; p=0.189 for heterogeneity). In addition, the
      heterogeneity disappeared when the analysis was restricted to Caucasians.
      CONCLUSION: Nuclear survivin expression is associated with poor prognosis for
      Caucasian NSCLC patients.

PMID- 22981351
TI  - Identification of a xanthinuria type I case with mutations of xanthine
      dehydrogenase in an Afghan child.
AB  - Xanthinuria due to xanthine dehydrogenase (XDH) deficiency is a rare genetic
      disorder characterized by hypouricemia and the accumulation of xanthine in the
      urine. We have identified an Afghan girl whose xanthinuria could be classified as
      type I xanthinuria based on an allopurinol loading test. Three mutations were
      identified in the XDH gene, 141insG, C2729T (T910M) and C3886T (R1296W). Site
      directed mutagenesis followed by expression analysis in Escherichia coli revealed
      that not only the frame shift mutation 141insG impairs XDH activity, but also the
      missense mutation C2729T, while C3886T resulted in major residual activity of
      about 50% of the wild type. In this report, a case of xanthinuria type I with
      mutations of XDH was identified and characterized by expression studies.

PMID- 22981352
TI  - Premature cystic lesions in shoulders of elite junior javelin and volleyball
      athletes: a comparative evaluation using 3.0 Tesla MRI.
AB  - BACKGROUND: The purpose of this study was to evaluate clinical and magnetic
      resonance imaging (MRI) findings in the shoulders of high performance competitive
      junior javelin athletes and volleyball players. The hypothesis was that
      structural lesions already exist in young and asymptomatic overhead athletes.
      METHODS: Thirty-one healthy high performance junior elite athletes were included.
      Group 1 consisted of 15 male javelin throwers (mean age, 17.7 +/- 0.8 years) and
      group 2 of 16 male volleyball players (16.9 +/- 1.0 years). Questionnaire-based
      interviews, comprehensive clinical examination, and shoulder scoring systems
      (visual analog scale [VAS] and Constant-Murley Score) were completed. Bilateral
      shoulder imaging was performed using a 3.0 Tesla MRI. RESULTS: The Constant
      Murley Score of group 1 was 95.5 +/- 3.6 and 94.7 +/- 4.6 points for group 2.
      Group 1 demonstrated a mean VAS of 0.9 +/- 1.6 and group 2 a mean of 0.6 +/- 0.8
      points. Postero-superior intraosseous cysts of the humeral head were detected in
      73.3% of all javelin throwers in the dominant shoulder, but only in 13.3% in the
      nondominant shoulder (P = .008). In the volleyball group, such cyst formation was
      rarely seen in 12.5% in the dominant versus 6.3% in the nondominant shoulder (P =
      .66). CONCLUSION: A high percentage of junior elite athletes already demonstrate
      osseus signs of overloading especially in the group of javelin athletes, although
      none had a history of prior shoulder pathology. Therefore, junior overhead
      athletes might be at risk for the early development of structural lesions at the
      insertion of the posterior rotator cuff similar to lesions already known for
      adult athletes, even though they do not present clinical signs of overuse at that
      age.

PMID- 22981353
TI  - Reconstruction for anterior sternoclavicular joint dislocation and instability.
AB  - BACKGROUND: Sternoclavicular joint (SCJ) instability is relatively rare. Surgical
      treatment may be considered for severely displaced dislocations or symptomatic
      recurrent anterior instability. The purpose of this study was to describe an SCJ
      ligament reconstruction technique and retrospectively evaluate its safety and
      effectiveness for treating anterior SCJ dislocations and instability. MATERIALS
      AND METHODS: A retrospective review of demographics, medical history, injury
      characteristics, and pretreatment pain and functional levels was performed. A
      soft-tissue graft woven in a Roman numeral X pattern through clavicular and
      sternum subcortical bone tunnels was used. Patients were evaluated with
      postoperative visual analog scale (VAS) and functional scores, and their ability
      to return to normal preoperative sports and activities was determined. RESULTS:
      Six patients were evaluated with a mean follow-up of 40 months (range, 24.5-58
      months). Injury mechanisms included acute trauma (3 patients), minor trauma (1
      patient), and chronic atraumatic instability (2 patients). The mean preoperative
      symptom duration was 11 months (range, 0.5-27.5 months). Autograft hamstring
      graft was used in all cases with no resulting surgical complications. All 6
      patients had full range of motion with no instability after treatment. Five
      patients had no pain (0 of 10 on VAS), whereas one patient had mild pain (1 to 3
      of 10 on VAS). All 6 patients had improved functional scores. All returned to
      preoperative activities and participation in sports. No recurrent instability
      occurred. In 1 case, failure occurred at 4 years with recurrent pain, and
      revision was performed. CONCLUSIONS: The results of our study indicate that
      reconstruction for anterior SCJ dislocation is safe with results comparable to
      previously described surgical stabilization techniques. This technique provides a
      surgical treatment option for symptomatic anterior SCJ dislocation and
      instability.

PMID- 22981354
TI  - Post-arthroscopic elbow chondrolysis after continuous intra-articular ropivacaine
      infusion.

PMID- 22981355
TI  - Hypercholesterolemia increases supraspinatus tendon stiffness and elastic modulus
      across multiple species.
AB  - BACKGROUND: More than one-quarter of Americans have hypercholesterolemia and/or
      are being treated with cholesterol-lowering medications. Given the systemic
      nature of hypercholesterolemia and remaining questions regarding its effect on
      tendons at a local level, we sought to assess the utility of small versus large
      animal model systems for translational studies by exploring the effect of
      hypercholesterolemia on supraspinatus tendon elastic mechanical properties in
      mice, rats, and monkeys. We hypothesized that stiffness and elastic modulus would
      be increased in tendons across species due to hypercholesterolemia. MATERIALS AND
      METHODS: Supraspinatus tendons from normal (control) and high-cholesterol (HC)
      mice, rats, and monkeys were used in this study. After dissection, tendons were
      geometrically measured and tensile tested with tissue strain measured optically.
      RESULTS: Overall, HC animals had significantly altered plasma lipid profiles.
      Biomechanical testing showed a significant increase in stiffness compared with
      control in HC mice and rats, as well as a nonsignificant trend for HC monkeys.
      Elastic modulus was also significantly increased in HC mice and monkeys, with HC
      rats showing a trend. CONCLUSIONS: The consistency of our findings across species
      and between small and large animals, combined with the fact that the aged mice
      were exposed to lifelong hypercholesterolemia (compared with rats and nonhuman
      primates, which were fed HC diets), suggests that these increased properties may
      be inherent to the effect of hypercholesterolemia on supraspinatus tendon rather
      than due to an effect of cumulative exposure time to the effects of HC. Further
      investigation is needed to confirm this concept.

PMID- 22981356
TI  - Histopathologic evaluation of passive stabilizers in shoulder instability.
AB  - BACKGROUND: The macroscopic pathomorphology in recurrent shoulder instability has
      been described. However, less is known regarding the histopathologic details of
      the affected structures. This study evaluates different histopathologic stages of
      shoulder instability by assessing biopsy specimens of static stabilizers for
      possible correlations with clinical parameters. Our hypothesis was that clinical
      parameters of shoulder instability correlate with histopathologic findings.
      MATERIALS AND METHODS: Passive shoulder stabilizers (labrum, anterior bundle of
      the inferior glenohumeral ligament) were biopsied during arthroscopic shoulder
      stabilization. Samples were submitted to immunohistochemistry, in situ
      hybridization, and blinded evaluation. Clinical data, comprising age (<30 years
      or >=30 years), total number of dislocations (1, 2-3, or >3), and period since
      initial dislocation (<6 months, 6 months to 6 years, or >6 years), were tested
      for statistical correlation with the following histopathologic parameters:
      inflammation, lipomatous changes, vascular proliferation, tissue fragmentation,
      and cellularity. RESULTS: Standardized biopsies were performed in 30 consecutive
      patients (4 women and 26 men; mean age, 32.6 years) with anterior shoulder
      instability. Microscopic evaluation showed only small variations in histologic
      changes among all samples. Only limited variations in cell density, matrix
      swelling, and collagen fiber disruptions were found. Immunohistochemical analysis
      showed a similar expression of decorin in all samples. Clinical parameters (age,
      total number of dislocations, and period since initial dislocation) were
      statistically independent from histopathologic parameters (inflammation,
      lipomatous changes, vascular proliferation, tissue fragmentation, and
      cellularity). No correlation was found in patients with 1 dislocation versus
      those with more than 1 dislocation. CONCLUSIONS: In contrast to macroscopic
      findings among different grades of shoulder instability, this study detected no
      correlation between clinical items (age, total number of dislocations, and period
      since initial dislocation) and histopathologic parameters. These clinical items
      seem to be independent from the tissue status of static stabilizers of the
      shoulder.

PMID- 22981357
TI  - Distal humeral coronal plane fractures: management, complications and outcome.
AB  - BACKGROUND: Coronal plane fractures of the distal humerus have special
      characteristics in classification, imaging, surgical approaches, materials used,
      treatment modalities, and complications. The purpose of this study is to comment
      on these topics. MATERIALS AND METHODS: A retrospective analysis was done for
      patients with distal humeral coronal plane fractures. They were classified
      according to Dubberley and functionally evaluated by Mayo Elbow Performance Index
      (MEPI). The long-term complications were evaluated. RESULTS: There were 15
      patients, with type 1 fractures in 2, type 2 in 6, and type 3 in 7. All patients
      were treated by open reduction and internal fixation either by lateral or
      posterior approach. The average MEPI score was 83.3 (range, 60-100) points with 7
      excellent, 2 good, and 6 fair results. The MEPI scores of type 3 fractures were
      significantly lower than those of types 1 and 2 fractures (P = .037 and P = .002,
      respectively). The complications were avascular necrosis in 4 (27%) patients,
      degenerative arthritis in 6 (40%), joint step-off in 6 (40%), heterotopic
      ossification in 7 (47%), nonunion in 1 (7%), and implant failure in 1 (7%). The
      presence of avascular necrosis and joint step-off were significantly associated
      with degenerative arthritis (P = .004 and P = .005, respectively). Heterotopic
      ossification was significantly associated with presence of lateral epicondyle
      fracture (P = .004). CONCLUSION: Type 1A and 2A coronal plane fractures typically
      had an excellent outcome. However, type 3 and subtype B fractures are prone to
      developing complications which are primarily avascular necrosis, degenerative
      arthritis and heterotopic ossification.

PMID- 22981358
TI  - Long-term results after ulnar collateral ligament reconstruction of the elbow in
      European athletes with interference screw technique and triceps fascia autograft.
AB  - BACKGROUND: In the last decade, there has been increasing interest in medial
      ulnar collateral ligament (MUCL) reconstruction techniques for MUCL insufficiency
      of the elbow. All case series are based on American and Asian Athletes and use
      primarily a palmaris longus tendon or gracilis tendon as an autograft in
      reconstructions. A new technique is the interference screw fixation. Evidence
      that supports the use of this technique is mainly from controlled laboratory
      studies. The purpose was to evaluate the interference screw technique for MUCL
      reconstructions in a European, clinical setting, with a triceps tendon fascia
      autograft. METHODS: Twenty consecutive athletes with diagnosed MUCL insufficiency
      who underwent a MUCL reconstruction using the interference screw technique were
      reviewed retrospectively. Indications for reconstruction were medial elbow pain
      and/or instability caused by insufficiency of the MUCL that prevented the athlete
      from sport activity after a minimum of 3 months of conservative treatment.
      RESULTS: At a mean follow-up of 55 months (range, 36-94), the mean Mayo Elbow
      Performance Index (MEPI) score improved from 82 to 91 points (range, 80-100); P <
      .001. In the end, 6 patients (30%) quit the sport activities they were
      preoperatively participating in, all because of reasons unrelated to the MUCL
      reconstruction. There were excellent results on the Conway scale in 18 patients.
      CONCLUSION: Good results are reported based on the postoperative MEPI and Conway
      scores with clinically stable MUCL reconstructions without signs of break-out or
      fractures on radiographic follow-up. However, the dropout, even after successful
      reconstruction in European athletes, is high.

PMID- 22981359
TI  - Organizing probabilistic models of perception.
AB  - Probability has played a central role in models of perception for more than a
      century, but a look at probabilistic concepts in the literature raises many
      questions. Is being Bayesian the same as being optimal? Are recent Bayesian
      models fundamentally different from classic signal detection theory models? Do
      findings of near-optimal inference provide evidence that neurons compute with
      probability distributions? This review aims to disentangle these concepts and to
      classify empirical evidence accordingly.

PMID- 22981360
TI  - Characterisation of dental pulp stem cells: a new horizon for tissue
      regeneration?
AB  - Stem cells possess multipotent properties that allow them to differentiate into
      various cells, which may be potentially useful in tissue regeneration. Stem cell
      populations are reported to be present in various tissues of hematopoietic,
      neural and mesenchymal lineages, with the presence of stem cell populations in
      dental pulp tissue first described more than 10 years ago. The main components of
      dental pulp tissue are dental pulp cells, which are mesenchymal cells derived
      from the neural crest.(1,2) Some of these cells demonstrate high growth potential
      and possess multiple differentiation properties, and have been designated dental
      pulp stem cells (DPSCs). These cell populations are present not only in adult
      pulp tissue, but also in deciduous tooth pulp and apical papilla. DPSCs isolated
      by different methods, such as high growth potential, using various surface
      markers, and high efflux of a fluorescent nuclear stain (Hoechst 33342), all show
      multipotency, however their surface marker expression is somewhat different from
      each other. In vivo studies have revealed the possibility use of DPSCs in the
      regeneration of various tissue. DPSCs are of dental pulp origin, and dental pulp
      tissue is regenerated from DPSCs. Many researchers have focused on the dentine-
      and bone-forming properties of DPSCs, but their neuronal and muscular
      differentiation capacity suggests they may have a wider clinical application.

PMID- 22981361
TI  - Efficacy and morbidity of surgical therapy in late-stage encapsulating peritoneal
      sclerosis.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but devastating
      complication of peritoneal dialysis composed of chronic abdominal pain, chronic
      ileus, and severe malnutrition. Operative therapy for EPS is a complex procedure,
      including perionectomy and enterolysis (PEEL). In contrast to simple
      adhesiolysis, PEEL comprises a restitution of intestinal passage and prevention
      of recurrent disease by decapsulation and partial deserosation. METHODS: We
      reviewed the treatment of patients with EPS at our referral center regarding
      perioperative morbidity, mortality, and long-term outcome. Only patients who
      underwent PEEL were included. Preoperative general status was ascertained by
      APACHE-II score and body mass index. Postoperative morbidity was stratified into
      minor and major complications. RESULTS: Between the years 2003 and 2010, 26 of 45
      patients with late-stage EPS underwent PEEL. Median age was 54 years, APACHE-II
      score was 15, and body mass index was 21 kg/m2. To achieve intestinal function, 9
      bowel resections with immediate anastomoses were necessary. Eleven patients (37%)
      received a complete parietal peritonectomy. Overall morbidity was 44%, with minor
      complications in 2 patients (7%) and major complications in 11 patients (31%).
      Three patients (10%) died within the first year after operative treatment.
      CONCLUSION: PEEL is a treatment option that can be performed with low mortality
      and acceptable morbidity. It is a precondition that these patients are treated in
      specialized referral centers.

PMID- 22981362
TI  - Long-term functional results from a randomized clinical study of transverse
      coloplasty compared with colon J-pouch after low anterior resection for rectal
      cancer.
AB  - BACKGROUND: The colonic pouch is considered as an alternative to the standard
      straight low anastomosis after resection for rectal cancer. The aim of this
      prospective randomized trial was to compare short- and long-term functional
      results of colonic J-pouch (CJP) and transverse coloplasty (TCP) after low
      anterior resection for rectal cancer. METHODS: Between 2000 and 2005, patients
      with mid or low rectal cancer scheduled for an elective sphincter-preserving
      resection were eligible. The primary end point was to compare bowel functional
      results 6 months and 3 years after ileostomy closure. Fecal incontinence score
      and a questionnaire that included items for clinical evaluation of bowel function
      were used. RESULTS: One-hundred six patients were randomized; 54 patients were
      allocated to the CJP group and 52 in the TCP group. There were no differences
      between the 2 groups in terms of demographic and clinical data. Overall,
      postoperative complication rate was 19.8% without differences between the groups.
      Two patients (1.9%; one in each group) presented with anastomotic dehiscence.
      Long-term incomplete evacuation rates were 29.2% in the CPT group and 33.3% in
      the CJP group, without substantial differences. Overall, short- and long-term
      functional outcomes of both procedures were comparable. No differences were
      observed in terms of fecal incontinence or in all the items included in the
      questionnaire. CONCLUSION: TCP reconstruction after rectal cancer resection and
      coloanal anastomosis is functionally similar to CJP both in short- and long-term
      outcomes. The TCP technique does not seem to improve significantly the incomplete
      defecation symptom respect to CJP. REGISTRATION NUMBER: NCT01396928;
      http://register.clinicaltrial.gov.

PMID- 22981363
TI  - Effects of amino acid substitutions at positions 33 and 37 on UDP
      glucuronosyltransferase 1A9 (UGT1A9) activity and substrate selectivity.
AB  - UGT1A9 contributes to the glucuronidation of numerous drugs and xenobiotics.
      There is evidence to suggest that the Met33Thr substitution, as occurs in the
      polymorphic variant UGT1A9*3, variably affects xenobiotic glucuronidation. The
      equivalent position in UGT1A4 is also known to influence enzyme activity, whilst
      an N-terminal domain histidine (His37 in UGT1A9) is believed to function as the
      catalytic base in most UGT enzymes. To elucidate the roles of key amino acids and
      characterise structure-function relationships, we determined the effects of amino
      acid substitutions at positions 33 and 37 of UGT1A9 on the kinetics of 4
      methylumbelliferone (4-MU), mycophenolic acid (MPA), propofol (PRO),
      sulfinpyrazone (SFZ), frusemide (FSM), (S)-naproxen (NAP) and retigabine (RTB)
      glucuronidation, compounds that undergo glucuronidation at either a phenolic (4
      MU, MPA, PRO), carboxylate (FSM, NAP), acidic carbon (SFZ) or amine (RTB)
      function. Substitution of Met33 with Val, Ile, Thr, and Gln, as occur in UGT1A1,
      UGT1A3, UGT1A4 and UGT1A6 respectively, variably affected kinetics and catalytic
      efficiency. Whilst K(m) values were generally higher and V(max) and CL(int)
      values were generally lower than for wild-type UGT1A9 with most substrate-mutant
      pairs, the pattern and the magnitude of the changes in each parameter differed
      substantially. Moreover, exceptions occurred; CL(int) values for MPA and FSM
      glucuronidation by the position-33 mutants were the same as or higher than that
      of UGT1A9. Mutation of His37 abolished activity towards all substrates, except
      RTB N-glucuronidation. The data confirm the importance of single amino acids for
      UGT enzyme activity and substrate selectivity, and support a pivotal role for
      residue-33 in facilitating substrate binding to UGT1A9.

PMID- 22981364
TI  - Japonicone A antagonizes the activity of TNF-alpha by directly targeting this
      cytokine and selectively disrupting its interaction with TNF receptor-1.
AB  - Anti-TNF biologics are effective therapies for various inflammatory diseases.
      Unfortunately, their clinical use is associated with an increased risk of
      infections. Selectively inhibiting TNF receptor-1 (TNFR1)-mediated signaling
      while preserving TNFR2 signaling may reduce inflammation yet maintain host immune
      response to pathogens. However, few small molecules that selectively target the
      TNF/TNFR system have been discovered. In the present study, we identified
      Japonicone A (Jap A), a nature compound derived from Inula japonica Thunb, as a
      novel TNF-alpha antagonist, as it reduced the TNF-alpha-mediated cytotoxicity on
      L929 cells and inhibited the binding of (125)I-labeled TNF-alpha to L929 cell
      surface. Furthermore, Jap A could directly bind to TNF-alpha rather than TNFR1 as
      determined by surface plasmon resonance. More importantly, Jap A could
      effectively inhibit the binding of TNF-alpha to TNFR1, while displaying only
      marginal inhibitory effects on that to TNFR2. Jap A also could block TNFR1
      mediated signaling as it inhibited TNF-alpha-induced NF-kappaB activation in 293
      cells. In addition, Jap A suppressed TNF-alpha-induced expressions of adhesion
      molecules (ICAM-1, VCAM-1) and chemokine (MCP-1) in the endothelial cells by
      blocking TNF-alpha-triggered multiple signaling pathways. Data from in vivo
      experiments demonstrated that Jap A protected mice from acute hepatitis induced
      by TNF-alpha/d-galactosamine, but did not compromise host antiviral immunity in
      adenovirus-infected mice. These results indicate that Jap A can directly target
      TNF-alpha, selectively disrupt its interaction with TNFR1, and antagonize its pro
      inflammatory activities without compromising host defense against virus, thus
      emphasizing the potential of Jap A as an interesting lead compound for
      development of new anti-inflammatory drugs.

PMID- 22981365
TI  - Evaluation of fluocinolone acetonide sustained release implant (Retisert)
      dissociation during implant removal and exchange surgery.
AB  - PURPOSE: To characterize the phenomenon of dissociation of the 2 components of
      the sustained-release fluocinolone acetonide implant (Retisert; Bausch & Lomb)
      during removal or exchange procedures, or both, and to evaluate outcomes after
      these events. DESIGN: Retrospective, observational case series. METHODS:
      Retrospective review of 27 consecutive sustained-release fluocinolone acetonide
      implant (Retisert) exchanges or removals between 2001 and 2010 at the Cole Eye
      Institute. All patients had received the implant as treatment for noninfectious
      uveitis. Preoperative and postoperative characteristics were analyzed, and
      operative reports were reviewed to characterize the effects of intraoperative
      implant dissociation. RESULTS: Twenty-seven sustained-release fluocinolone
      acetonide implant (Retisert) exchange or removal surgeries were performed by 3
      surgeons in 20 eyes of 19 patients. Of these 27 procedures, dissociation of the
      implant strut from the drug-containing cup occurred in 11 eyes (40.7%). Retrieval
      of the dislocated cup led to intraoperative complications, including posterior
      retinal tear (n = 1) and limited suprachoroidal hemorrhage (n = 1). The length of
      time that the implant resided in the eye correlated significantly with cup
      dissociation. Dissociated implants resided a mean of 47.4 months, whereas intact
      implants resided a mean of 32.5 months (P = .0032). There was no long-term or
      short-term vision loss attributed to intraoperative implant dissociation.
      CONCLUSIONS: Sustained-release fluocinolone acetonide implant (Retisert)
      dissociation is a common occurrence in exchange or removal procedures, or both.
      The longer an implant resided in the eye, the greater the tendency toward
      dissociation. Preparation for this complication should be contemplated in any
      implant removal or exchange procedure.

PMID- 22981366
TI  - Suture slippage in knotless suture anchors as a potential failure mechanism in
      rotator cuff repair.
AB  - PURPOSE: To quantify the strength of suture fixation of knotless suture anchors
      in relation to the anchors' pullout strength and to compare these results with
      the static friction between different sutures and anchor materials. METHODS:
      Suture slippage within the anchor and pullout strength of 4 different knotless
      suture anchor models were assessed in a bovine bone model. Furthermore, the peak
      force before onset of slippage of different sutures trapped between increasingly
      loaded 4-mm rods made of commonly used anchor material (polyetheretherketone,
      poly-L-lactide acid, metal) was assessed. RESULTS: In all but 1 of the tested
      anchors, there was a relevantly lower load needed for slippage of the sutures
      than to pull out the anchor from bone. The mean load to anchor pullout ranged
      between 156 and 269 N. The load to suture slippage ranged between 66 and 109 N.
      All sutures were better held between the metal rods (mean, 21; 95% confidence
      interval [CI], 19.2 to 23.3) than with polyetheretherketone rods (mean, 17; 95%
      CI, 15.7 to 18.1) or poly-L-lactide acid rods (mean, 18; 95% CI, 17.6 to 18.4).
      CONCLUSIONS: In the case of suture anchors that hold the sutures by clamping, the
      hold of the suture in the anchor may be far lower than the pullout strength of
      the anchor from bone, because the sutures just slip out from the anchor through
      the clamping mechanism. This is well explained by the low static friction
      achieved between the tested sutures and the test rods made of anchor materials.
      CLINICAL RELEVANCE: The use of knotless suture anchors appears quick and easy to
      perform; however, most of the anchor systems could not even reach half of the
      anchor pullout strength from bone before suture slippage occurred.

PMID- 22981368
TI  - Mapping Abbreviated Injury Scale data from 1990 to 1998 versions: a stepping
      stone in the contemporary evaluation of trauma.
AB  - INTRODUCTION: Many trauma registries have used the 1990 revision of the
      Abbreviated Injury Scale (AIS; AIS90) to code injuries sustained by trauma
      patients. Due to changes made to the AIS codeset since its release, AIS90-coded
      data lacks currency in the assessment of injury severity. The ability to map
      between the 1998 revision of AIS (AIS98) and the current (2008) AIS version
      (AIS08) already exists. The development of a map for transforming AIS90-coded
      data into AIS98 would therefore enable contemporary injury severity estimates to
      be derived from AIS90-coded data. METHODS: Differences between the AIS90 and
      AIS98 codesets were identified, and AIS98 maps were generated for AIS90 codes
      which changed or were not present in AIS98. The effectiveness of this map in
      describing the severity of trauma using AIS90 and AIS98 was evaluated using a
      large state registry dataset, which coded injury data using AIS90 over several
      years. Changes in Injury Severity Scores (ISS) calculated using AIS90 and mapped
      AIS98 codesets were assessed using three distinct methods. RESULTS: Forty-nine
      codes (out of 1312) from the AIS90 codeset changed or were not present in AIS98.
      Twenty-four codes required the assignment of maps to AIS98 equivalents. AIS90
      coded data from 78,075 trauma cases were used to evaluate the map. Agreement in
      calculated ISS between coded AIS90 data and mapped AIS98 data was very high
      (kappa=0.971). The ISS changed in 1902 cases (2.4%), and the mean difference in
      ISS across all cases was 0.006 points. The number of cases classified as major
      trauma using AIS98 decreased by 0.8% compared with AIS90. A total of 3102 cases
      (4.0%) sustained at least one AIS90 injury which required mapping to AIS98.
      CONCLUSIONS: This study identified the differences between the AIS90 and AIS98
      codesets, and generated maps for the conversion process. In practice, the
      differences between AIS90- and AIS98-coded data were very small. As a result,
      AIS90-coded data can be mapped to the current AIS version (AIS08) via AIS98, with
      little apparent impact on the functional accuracy of the mapped dataset produced.

PMID- 22981367
TI  - Anxioselective anxiolytics: on a quest for the Holy Grail.
AB  - The discovery of benzodiazepine receptors provided the impetus to discover and
      develop anxioselective anxiolytics ('Valium without the side effects'). The
      market potential for an anxioselective based on the gamma-aminobutyric acid A
      (GABA(A)) receptor resulted in clinical trials of multiple compounds. In contrast
      to the anxioselective profile displayed in preclinical models, compounds such as
      bretazenil, TPA023, and MRK 409 produced benzodiazepine-like side effects
      (sedation, dizziness) in Phase I studies, whereas alpidem and ocinaplon exhibited
      many of the characteristics of an anxioselective in the clinic. Alpidem was
      briefly marketed for the treatment of anxiety, but was withdrawn because of liver
      toxicity. Reversible elevations in liver enzymes halted development of ocinaplon
      in Phase III. The clinical profiles of these two molecules demonstrate that it is
      possible to develop GABA(A) receptor-based anxioselectives. However, despite the
      formidable molecular toolbox at our disposal, we are no better informed about the
      GABA(A) receptors responsible for an anxioselective profile in the clinic. Here,
      I discuss the evolution of a quest, spanning four decades, for molecules that
      retain the rapid and robust anti-anxiety actions of benzodiazepines without the
      side effects that limit their usefulness.

PMID- 22981369
TI  - Plant stanols induce intestinal tumor formation by up-regulating Wnt and EGFR
      signaling in Apc Min mice.
AB  - The rate of APC mutations in the intestine increases in middle-age. At the same
      period of life, plant sterol and stanol enriched functional foods are introduced
      to diet to lower blood cholesterol. This study examined the effect of plant
      stanol enriched diet on intestinal adenoma formation in the Apc(Min) mouse.
      Apc(Min) mice were fed 0.8% plant stanol diet or control diet for nine weeks.
      Cholesterol, plant sterols and plant stanols were analyzed from the caecum
      content and the intestinal mucosa. Levels of beta-catenin, cyclin D1, epidermal
      growth factor receptor (EGFR) and extracellular signal-regulated kinase 1/2
      (ERK1/2) were measured from the intestinal mucosa by Western blotting. Gene
      expression was determined from the intestinal mucosa using Affymetrix and the
      data were analyzed for enriched categories and pathways. Plant stanols induced
      adenoma formation in the small intestine, however, the adenoma size was not
      affected. We saw increased levels of nuclear beta-catenin, phosphorylated beta
      catenin (Ser675 and Ser552), nuclear cyclin D1, total and phosphorylated EGFR and
      phosphorylated ERK1/2 in the intestinal mucosa after plant stanol feeding. The
      Affymetrix data demonstrate that several enzymes of cholesterol synthesis pathway
      were up-regulated, although the cholesterol level in the intestinal mucosa was
      not altered. We show that plant stanols induce adenoma formation by activating
      Wnt and EGFR signaling. EGFR signaling seems to have promoted beta-catenin
      phosphorylation and its translocation into the nucleus, where the expression of
      cyclin D1 was increased. Up-regulated cholesterol synthesis may partly explain
      the increased EGFR signaling in the plant stanol-fed mice.

PMID- 22981371
TI  - Mevalonate-suppressive dietary isoprenoids for bone health.
AB  - Osteoclastogenesis and osteoblastogenesis, the balancing acts for optimal bone
      health, are under the regulation of small guanosine triphosphate-binding proteins
      (GTPases) including Ras, Rac, Rho and Rab. The activities of GTPases require post
      translational modification with mevalonate-derived prenyl pyrophosphates.
      Mevalonate deprivation induced by competitive inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG CoA) reductase (e.g., statins) prevents the
      activation of GTPases, suppresses the expression of the receptor for activation
      of nuclear factor kappa B (NFkappaB) ligand (RANKL) and activation of NFkappaB
      and, consequently, inhibits osteoclast differentiation and induces osteoclast
      apoptosis. In contrast, statin-mediated inactivation of GTPases enhances alkaline
      phosphatase activity and the expression of bone morphogenetic protein-2, vascular
      epithelial growth factor, and osteocalcin in osteoblasts and induces osteoblast
      proliferation and differentiation. Animal studies show that statins inhibit bone
      resorption and increase bone formation. The anabolic effect of statins and other
      mevalonate pathway-suppressive pharmaceuticals resembles the anti
      osteoclastogenic and bone-protective activities conferred by dietary isoprenoids,
      secondary products of plant mevalonate metabolism. The tocotrienols, vitamin E
      molecules with HMG CoA reductase-suppressive activity, induce mevalonate
      deprivation and concomitantly suppress the expression of RANKL and cyclooxygenase
      2, the production of prostaglandin E2 and the activation of NFkappaB.
      Accordingly, tocotrienols inhibit osteoclast differentiation and induce
      osteoclast apoptosis, impacts reminiscent of those of statins. In vivo studies
      confirm the bone protective activity of tocotrienols at nontoxic doses. Blends of
      tocotrienols, statins and isoprenoids widely found in fruits, vegetables, grains,
      herbs, spices, and essential oils may synergistically suppress osteoclastogenesis
      while promoting osteoblastogenesis, offering a novel approach to bone health that
      warrants clinical studies.

PMID- 22981370
TI  - Increased inflammatory response in aged mice is associated with age-related zinc
      deficiency and zinc transporter dysregulation.
AB  - Aging is a complex process associated with physiological changes in numerous
      organ systems. In particular, aging of the immune system is characterized by
      progressive dysregulation of immune responses, resulting in increased
      susceptibility to infectious diseases, impaired vaccination efficacy and systemic
      low-grade chronic inflammation. Increasing evidence suggest that intracellular
      zinc homeostasis, regulated by zinc transporter expression, is critically
      involved in the signaling and activation of immune cells. We hypothesize that
      epigenetic alterations and nutritional deficits associated with aging may lead to
      zinc transporter dysregulation, resulting in decreases in cellular zinc levels
      and enhanced inflammation with age. The goal of this study was to examine the
      contribution of age-related zinc deficiency and zinc transporter dysregulation on
      the inflammatory response in immune cells. The effects of zinc deficiency and age
      on the induction of inflammatory responses were determined using an in vitro cell
      culture system and an aged mouse model. We showed that zinc deficiency,
      particularly the reduction in intracellular zinc in immune cells, was associated
      with increased inflammation with age. Furthermore, reduced Zip 6 expression
      enhanced proinflammatory response, and age-specific Zip 6 dysregulation
      correlated with an increase in Zip 6 promoter methylation. Furthermore, restoring
      zinc status via dietary supplementation reduced aged-associated inflammation. Our
      data suggested that age-related epigenetic dysregulation in zinc transporter
      expression may influence cellular zinc levels and contribute to increased
      susceptibility to inflammation with age.

PMID- 22981373
TI  - Rapid, severe neurological impairment associated with paraneoplastic cerebellar
      degeneration and anti-Yo antibodies.

PMID- 22981372
TI  - Cultural adaptation of an evidence-based nursing intervention to improve
      medication adherence among people living with HIV/AIDS (PLWHA) in China.
AB  - BACKGROUND: Adapting nursing interventions to suit the needs and culture of a new
      population (cultural adaptation) is an important early step in the process of
      implementation and dissemination. While the need for cultural adaptation is
      widely accepted, research-based strategies for doing so are not well articulated.
      Non-adherence to medications for chronic disease is a global problem and cultural
      adaptation of existing evidence-based interventions could be useful. OBJECTIVES:
      This paper aims to describe the cultural adaptation of an evidence-based nursing
      intervention to improve medication adherence among people living with HIV/AIDS
      and to offer recommendations for adaptation of interventions across cultures and
      borders. SITE: The intervention, which demonstrated efficacy in a randomized
      controlled trial in North America, was adapted for the cultural and social
      context of Hunan Province, in south central China. SOURCES OF DATA: The
      adaptation process was undertaken by intervention stakeholders including the
      original intervention study team, the proposed adaptation team, and members of a
      Community Advisory Board, including people living with HIV/AIDS, family members,
      and health care workers at the target clinical sites. PROCEDURES: The adaptation
      process was driven by quantitative and qualitative data describing the new
      population and context and was guided by principles for cultural adaptation drawn
      from prevention science research. RESULTS: The primary adaptation to the
      intervention was the inclusion of family members in intervention activities, in
      response to the cultural and social importance of the family in rural China. In a
      pilot test of the adapted intervention, self-reported medication adherence
      improved significantly in the group receiving the intervention compared to the
      control group (p=0.01). Recommendations for cultural adaptation of nursing
      interventions include (1) involve stakeholders from the beginning; (2) assess the
      population, need, and context; (3) evaluate the intervention to be adapted with
      attention to details of the original studies that demonstrated efficacy; (4)
      compare important elements of the original intervention with those of the
      proposed new population and context to identify primary points for adaptation;
      (5) explicitly identify sources of tension between intervention fidelity and
      cultural adaptive needs; (6) document the process of adaptation, pilot the
      adapted intervention, and evaluate its effectiveness before moving to
      dissemination and implementation on a large scale.

PMID- 22981374
TI  - [Respect for dementia patients' autonomy and the need for interdisciplinary
      cooperation].

PMID- 22981375
TI  - ?

PMID- 22981376
TI  - Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a
      randomised controlled trial in patients with schizophrenia and healthy controls.
AB  - The objective of this study was to examine exercise effects on global brain
      volume, hippocampal volume, and cortical thickness in schizophrenia patients and
      healthy controls. Irrespective of diagnosis and intervention, associations
      between brain changes and cardiorespiratory fitness improvement were examined.
      Sixty-three schizophrenia patients and fifty-five healthy controls participated
      in this randomised controlled trial. Global brain volumes, hippocampal volume,
      and cortical thickness were estimated from 3-Tesla MRI scans. Cardiorespiratory
      fitness was assessed with a cardiopulmonary ergometer test. Subjects were
      assigned exercise therapy or occupational therapy (patients) and exercise therapy
      or life-as-usual (healthy controls) for six months 2h weekly. Exercise therapy
      effects were analysed for subjects who were compliant at least 50% of sessions
      offered. Significantly smaller baseline cerebral (grey) matter, and larger third
      ventricle volumes, and thinner cortex in most areas of the brain were found in
      patients versus controls. Exercise therapy did not affect global brain and
      hippocampal volume or cortical thickness in patients and controls.
      Cardiorespiratory fitness improvement was related to increased cerebral matter
      volume and lateral and third ventricle volume decrease in patients and to
      thickening in the left hemisphere in large areas of the frontal, temporal and
      cingulate cortex irrespective of diagnosis. One to 2h of exercise therapy did not
      elicit significant brain volume changes in patients or controls. However,
      cardiorespiratory fitness improvement attenuated brain volume changes in
      schizophrenia patients and increased thickness in large areas of the left cortex
      in both schizophrenia patients and healthy controls.

PMID- 22981377
TI  - Quantifying errors in the estimation of tuberculosis mortality in a population of
      South African miners.
AB  - BACKGROUND: All-cause mortality, based on national tuberculosis programme (NTP)
      register deaths, may under- or overestimate tuberculosis (TB) specific mortality
      in the population. OBJECTIVE: To assess the factors influencing this measurement
      in a single large population with high TB prevalence and mortality. METHODS:
      Routinely collected data on TB cases and treatment outcomes were linked to
      population data from a cohort of South African miners from 1995 to 2008. Vital
      status and cause of death were determined from multiple sources, including the TB
      programme, death register and autopsy. RESULTS: The TB mortality rate, based on
      430 deaths on the TB register, was 192/100,000 person-years (py). Many of these
      deaths (57%) were not caused by TB, and 483 TB deaths were identified outside the
      programme. Overall, there were 674 TB-specific deaths; the TB-specific mortality
      rate was 302/100,000 py. These deaths included 191 (28%) on the TB register, 23
      (3%) among defaulters/transfers, 153 (23%) after anti-tuberculosis treatment and
      307 (46%) in men who had never been on the programme. CONCLUSIONS: This study
      highlights methodological issues in estimating TB mortality. In this population,
      a method using the product of TB incidence and case fatality consistently
      underestimated TB mortality. Accurate estimates of TB-specific mortality are
      crucial for the proper evaluation of TB control programmes.

PMID- 22981378
TI  - Functional significance of the copper transporter ATP7 in peptidergic neurons and
      endocrine cells in Drosophila melanogaster.
AB  - The Drosophila ATP7 copper transporter has sequence homology to the human copper
      transporters ATP7A and ATP7B, which are defective in Menkes and Wilson disease,
      respectively. We show here that in Drosophila ATP7 is expressed by many
      peptidergic neurons. As C-terminal amidation of neuropeptides depends on the
      copper-containing enzyme PHM, it seemed likely that in the absence of ATP7 the
      activity of PHM might be compromised. Indeed, inhibition of ATP7 expression by
      RNAi led to a decrease in mature amidated neuropeptides and the appearance of C
      terminally Gly-extended neuropeptides. The strength of this effect differed from
      one cell type to another; it was very pronounced for AKH and corazonin, but much
      less so for SIFamide and myosuppressin. Nevertheless, down-regulation of ATP7
      specifically in the SIFamide-expressing neurons resulted in male-male courtship
      behavior.

PMID- 22981379
TI  - Response to Rawlins et al.: 'Reproductive health services in Malawi: an
      evaluation of a quality improvement intervention'.

PMID- 22981380
TI  - Struggling for motherhood with an intellectual disability--a qualitative study of
      women's experiences in Sweden.
AB  - OBJECTIVE: to gain a deeper understanding of the experiences of childbearing in
      women with intellectual disabililty (ID). DESIGN/SETTING: ten women with ID, who
      had given birth within seven years, were interviewed twice and data were analysed
      with content analysis. FINDINGS: the overarching theme was: Struggling for
      motherhood with an ID. The significance of having an intellectual disability
      became evident when the women encountered mixed reactions from partners and
      relatives, who sometimes suggested an induced abortion. The women disclosed their
      diagnosis if they believed it was beneficial for them. Throughout the process the
      women also felt anxious and distressed about the custody of the child. Women
      experienced the pregnancy as a physical and psychological transition. It was
      mostly a happy and responsible life event, and the women were aware of physical
      signs in their bodies and contact with the unborn child. Parent education was
      considered important but not adequately adapted to their needs. The women
      described the delivery as hard and painful work, sometimes difficult to
      understand and they had different strategies to handle the pain and strain of
      labour. The child was welcomed with warmth and curiosity by the women, who cared
      for and breast fed the child even if the hospital environment could be confusing
      and continued custody not taken for granted. CONCLUSIONS: women with ID struggle
      for motherhood and fear losing custody of the child. Professionals need to
      identify and support these women, who may not always disclose their diagnosis.
      Since pregnancy, delivery and the transition into motherhood can be difficult to
      understand, information and support should be better tailored to their needs.

PMID- 22981381
TI  - Diallyl trisulfide induces apoptosis in human breast cancer cells through ROS
      mediated activation of JNK and AP-1.
AB  - Multiple lines of evidence support an inverse association between consumption of
      garlic and the risk of cancer. Chemopreventive effects of garlic have been
      attributed to its oil-soluble sulfur ingredients, such as diallyl sulfide (DAS),
      diallyl disulfide (DADS), and diallyl trisulfide (DATS), but their underlying
      molecular mechanisms remain largely unresolved. In the present study, we found
      that DATS showed the most potent anti-proliferative effects in human breast
      cancer MCF-7 cells. MCF-7 cells treated with DATS underwent apoptotic death as
      revealed by a progressive increase in the proportion of the sub-G0/G1 cell
      population and a typical pattern of annexin V/propidium iodide staining. DATS
      induced phosphorylation of the antiapoptotic Bcl-2 and proteolytic cleavage of
      poly(ADP-ribose)polymerase (PARP) in MCF-7 cells. DATS treatment activated c-Jun
      N-terminal kinase (JNK). DATS-induced apoptosis was blunted in MCF-7 cells
      treated with a specific JNK inhibitor SP600125 or transiently transfected with
      dominant negative JNK. DATS treatment resulted in accumulation of reactive oxygen
      species (ROS). DATS-induced apoptosis as well as activation of JNK was abrogated
      by N-acetyl-l-cysteine (NAC). Furthermore, DATS induced phosphorylation and
      expression of c-Jun, which were attenuated by NAC. MCF-7 cells treated with DATS
      also exhibited increased DNA binding activity of AP-1, which was blocked by NAC
      and the JNK inhibitor. Proteolytic cleavage of PARP induced by DATS was abrogated
      in the cells transfected with c-jun siRNA. Oral administration of 5MUmol/kg DATS
      to female Balb/c mice inhibited the growth of human MCF-7 cell tumor xenografts.
      These results suggest that DATS-induced apoptosis is mediated through ROS
      generation and subsequent activation of JNK and AP-1.

PMID- 22981382
TI  - Molecular insight in the multifunctional activities of Withaferin A.
AB  - Herbal medicine which involves the use of plants for their medicinal value, dates
      as far back as the origin of mankind and demonstrates an array of applications
      including cardiovascular protection and anti-cancer activities, via antioxidant,
      anti-inflammatory and metabolic activities. Even today the popularity of
      medicinal herbs is still growing like in traditional medicines such as the Indian
      medicine, Ayurveda. One of the Ayurvedic medicinal plants is Withania somnifera
      Dunal, of which the important constituents are the withanolides. Among them,
      Withaferin A is one of the most bioactive compounds, exerting anti-inflammatory,
      pro-apoptotic but also anti-invasive and anti-angiogenic effects. In the context
      of modern pharmacology, a better insight in the underlying mechanism of the broad
      range of bioactivities exerted by Withaferin A is compulsory. Therefore, a lot of
      effort was made to explore the intracellular effects of Withaferin A and to
      characterize its target proteins. This review provides a decisive insight on the
      molecular basis of the health-promoting potential of Withaferin A.

PMID- 22981383
TI  - Endogenously synthesized n-3 polyunsaturated fatty acids in fat-1 mice ameliorate
      high-fat diet-induced non-alcoholic fatty liver disease.
AB  - Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have well-documented
      protective effects against obesity-induced insulin resistance and hepatic
      steatosis. Here, we investigated the effects of endogenous n-3 PUFAs on diet
      induced fatty liver disease using fat-1 transgenic mice (fat-1) capable of
      converting n-6 to n-3 PUFAs. Wild-type (WT) and fat-1 mice were maintained on a
      high-fat diet (HFD) for 5months. HFD-induced weight gain and fatty liver were
      more prominent in WT mice than fat-1 mice. Histological analysis indicated that
      WT mice fed the HFD developed moderate-to-severe macrovesicular steatosis,
      whereas fat-1 mice developed very mild steatosis. In addition, HFD-induced
      hepatocyte ballooning and fibrosis were ameliorated in fat-1 mice. Serum alanine
      transaminase (ALT) and aspartate transaminase (AST) levels were within the
      respective normal ranges in HFD-fed fat-1 mice, whereas both were significantly
      elevated in HFD-fed WT mice. The fat-1 mice showed significantly decreased serum
      lipid levels, including triglycerides, total cholesterol (TC), HDL-C, and LDL-C,
      compared to WT mice regardless of diet. Specifically, the increases in very low
      density lipoprotein cholesterol (VLDL-C) and chylomicrons detected in HFD-fed WT
      mice were completely blunted in HFD-fed fat-1 mice. Gene expression analysis
      showed that hepatic Cyp7a1 mRNA and protein expression levels were markedly
      increased in HFD-fed fat-1 mice. In addition, genes involved in cholesterol
      uptake (Ldlr) and bile acid excretion (Abcg5 and Abcg8) were increased in the
      livers of fat-1 mice. These data suggest that n-3 PUFAs ameliorate diet-induced
      hyperlipidemia and fatty liver through induction of CYP7A1 expression and
      activation of cholesterol catabolism to bile acid.

PMID- 22981384
TI  - The foreskin advancement flap: an alternative technique for reconstruction of
      penile burns.
AB  - Penile burns are devastating injuries and are frequently associated with
      significant functional and psychological sequelae. The goals of penile
      reconstruction after burn injury include: 1) skin coverage, 2) preservation of
      penile length, sensation and erectile function, 3) esthetic integrity, and 4)
      permissive for penile growth in the pediatric patient. A multitude of different
      techniques have been proposed, including skin grafts, local, regional, and free
      flaps, each of which fail to address all goals of reconstruction. We introduce
      the foreskin advancement flap that, when available, successfully addresses these
      key challenges and as such provides for an ideal reconstruction.

PMID- 22981385
TI  - Use of adjunctive palmaris longus abductorplasty (Camitz) tendon transfer in
      pediatric median nerve injury.
AB  - A number of tendon transfers have been described for opponensplasty. Transfer of
      the palmaris longus (PL) tendon with a palmar fascial extension was initially
      described by Camitz. This technique has mostly been combined with carpal tunnel
      release in patients with long standing median neuropathy with atrophy of the
      thenar muscles. However, the Camitz transfer has not been previously described in
      the setting of pediatric median nerve injury. We report 4 cases of Camitz
      transfer in pediatric patients with median nerve injuries. Four children (all
      female; age range 3-15 yrs) underwent PL tendon transfer following median nerve
      injury. The causes of injury included trauma, iatrogenic injury, and neuritis of
      the brachial plexus. The Camitz procedure was performed at the time of median
      nerve decompression and/or reconstruction. All patients had excellent early
      return of function. Transfer of the palmaris longus tendon reliably restores
      palmar abduction, with minimal to no additional morbidity, in carefully selected
      pediatric patients with median nerve injury undergoing release of the carpal
      tunnel.

PMID- 22981386
TI  - A quantitative analysis of the venous outflow of the deep inferior epigastric
      flap (DIEP) based on the perforator veins and the efficiency of superficial
      inferior epigastric vein (SIEV) supercharging.
AB  - BACKGROUND: While the arterial perfusion of the anterior abdominal wall has been
      extensively described in the literature, little has been published on the venous
      drainage of the deep inferior epigastric flap (DIEP). The present study was
      performed to further clarify the venous drainage of DIEP flap, which remains a
      common vascular complication of this flap. METHODS: We assessed the efficiency of
      venous outflow on 19 patients undergoing DIEP flap breast reconstruction,
      determining relative haemoglobin concentration (rHB) as an indicator of venous
      congestion. After the flap had been isolated on the perforator vessels, a
      selective clamping and declamping of the single lateral and medial perforator was
      performed and several measurements were carried out using a micro-lightguide
      spectrophotometer device (O2C: Oxygen to See; LEA Medizintechnik, Giebetaen,
      Germany). In addition, the efficacy of venous supercharging with ipsilateral and
      contralateral superficial inferior epigastric veins (SIEVs) was quantified.
      RESULTS: For the sake of simplicity, we applied the classic perfusion zones of
      the lower abdomen as suggested by Hartrampf (1983). Regardless of lateral or
      medial DIEP perforator veins, zone IV showed the least venous outflow, while we
      observed the highest drainage in zone I. There was no significant difference
      between the venous drainage of the two immediately adjacent zones II and III.
      Supercharging with the contralateral SIEV showed a significantly better venous
      drainage in the contralateral zones II and IV, whereas the ipsilateral SIEV did
      not present any significant improvement in the venous drainage of any zone.
      CONCLUSION: This study evaluated the characteristics of the venous outflow of the
      DIEP flap, based on the single perforator and the SIEVs. Our findings revealed
      that zones II and III have a similar venous drainage regardless of the perforator
      veins used. The supercharging of the contralateral SIEV leads to an improved
      venous outflow compared to the ipsilateral SIEV. This may support surgeons in
      minimising venous complications and may improve the degree of DIEP flap survival.

PMID- 22981387
TI  - A novel way to repair the earlobe after ear-gauging.

PMID- 22981388
TI  - The future of induction chemotherapy for head and neck squamous cell carcinoma.

PMID- 22981389
TI  - Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem
      cells for amelioration of post-irradiation salivary gland damage.
AB  - OBJECTIVES: External irradiation in head and neck cancers may induce irreversible
      hyposalivation and consequent xerostomia, stemming from radiation damage to
      salivary glands (SGs). As cell-based therapy has been reported to be able to
      repair or restore damaged SG tissues, we attempted to determine whether bone
      marrow-derived clonal mesenchymal stem cells (BM-cMSCs) can ameliorate
      irradiation-induced salivary gland damage via a murine model. METHODS: External
      irradiation at a dose of 15Gy was delivered to the neck fields of C57BL/6 mice.
      We directly administered either homologous mouse BM-cMSCs labeled with PKH26
      (treatment group) or PBS (control group) into SGs 24h after irradiation. Salivary
      flow rate (SFR) and lag time of salivation were measured at 12weeks after
      transplantation. At 4 and 12weeks post-transplantation, we performed
      morphological, histological, and immunofluorescent examinations.
      Transdifferentiation of administered BM-cMSCs into salivary epithelial cells was
      observed by confocal microscopy. RESULTS: SFR was significantly increased in BM
      cMSCs-transplanted mice compared with PBS-injected mice at 12weeks after
      transplantation. Administration of BM-cMSCs preserved the microscopic
      morphologies of SGs, with more functional acini in BM-cMSC-transplanted SGs than
      in PBS-injected SGs. Immunofluorescent staining revealed less apoptotic cells and
      increased microvessel density in BM-cMSC-transplanted SGs compared with PBS
      injected SGs. PKH-26 labeled BM-cMSCs were detected in transplanted SGs at 4weeks
      after transplantation and in vivo transdifferentiation of BM-cMSCs into acinar
      cells was also observed. CONCLUSION: This study suggests that BM-cMSCs can
      ameliorate salivary damage following irradiation and can be used as a source of
      cell-based therapy for restoration of irradiation-induced salivary hypofunction.

PMID- 22981390
TI  - Microfiltration method of removal of bacterial contaminants and their monitoring
      by nitric oxide and Limulus assays.
AB  - Similar to lipopolysaccharide (LPS), a product of Gram-negative bacteria, the
      signal macromolecules of Gram-positive bacteria lipoteichoic acid (LTA) and
      peptidoglycan (PGN) possess multiple biological activities. They may be a source
      of misinterpretation of experimental findings. We have found that not only LPS
      but also LTA and PGN can be detected by the Limulus amebocyte lysate (LAL) assay.
      All of them stimulate the high output in vitro nitric oxide (NO) production of in
      rat peritoneal cells. The onset of the NO enhancement was observed with 25
      100pg/ml of LPS and 25-100ng/ml of PGN and LTA. Polymyxin B (PMX), if applied at
      concentration 10,000-fold higher than that of LPS, can completely inhibit the NO
      and LAL binding responses of LPS. The NO-stimulatory and LAL-binding properties
      of LTA and PGN are not eliminated by PMX. Handling of LPS contamination with PMX
      may be associated with serious problems because it possesses intrinsic biological
      activity and becomes cytotoxic at concentration >25MUg/ml. The present findings
      suggest a convenient alternative avoiding these issues. As monitored by the NO
      and LAL assays, even high amounts of LPS as well as PGN and LTA can be removed by
      molecular mass cutoff microfiltration. All types of the filters (3kDa to 100kDa)
      are equally effective. It is suggested that the microfiltration procedure may be
      considered as a preferable, general and easy method of sample decontamination.

PMID- 22981391
TI  - Multilocus sequence analysis of the actinobacterial genus Kribbella.
AB  - Multilocus sequence analysis (MLSA) was used to refine the phylogenetic analysis
      of the genus Kribbella, which currently contains 17 species with validly
      published names. Sequences were obtained for the 16S rRNA, gyrB, rpoB, recA, relA
      and atpD genes for 16 of the 17 type strains of the genus plus seven non-type
      strains. A five-gene concatenated sequence of 4099 nt was used to examine the
      phylogenetic relationships between the species of the genus Kribbella. Using the
      concatenated sequence of the gyrB-rpoB-recA-relA and atpD genes, most Kribbella
      type strains can be distinguished by a genetic distance of >0.04. Each single
      gene tree had an overall topology similar to that of the concatenated sequence
      tree. The single-gene relA tree, used here for the first time in MLSA of
      actinobacteria, had good bootstrap support, comparable to the rpoB and atpD gene
      trees, which had topologies closest to that of the concatenated sequence tree.
      This illustrates that relA is a useful addition in MLSA studies of the genus
      Kribbella. We propose that concatenated gyrB-rpoB-recA-relA-atpD gene sequences
      be used for examining the phylogenetic relationships within the genus Kribbella
      and for determining the closest phylogenetic relatives to be used for taxonomic
      comparisons.

PMID- 22981392
TI  - Vaccines and antibiotic resistance.
AB  - Vaccines and antibiotics have significantly contributed to improve health and
      also to increase the longevity of human beings. The fast-acting effect of
      antibiotics makes them indispensable to treat infected patients. Likewise, when
      the causative agent of the infection is unknown and in cases of superinfections
      with different species of bacteria, antibiotics appear to be the only therapeutic
      option. On the contrary, vaccines are usually not efficacious in people already
      infected and their action is generally limited to a much narrowed range of
      pathogens. However, vaccines have contributed to the eradication of some of the
      most deadly infectious agents worldwide, can generate immunity to infections
      lasting for several years or life-long, and are able to induce herd immunity.
      Nonetheless, infectious diseases are still among the leading causes of morbidity
      and mortality worldwide. This is mainly owing to the emergence of bacterial
      resistance to antibiotics and the lack of efficacious medications to treat
      several other infectious diseases. Development of new vaccines appears to be a
      promising solution to these issues. Indeed, with the advent of new discovery
      approaches and adjuvants, today is possible to make vaccines virtually against
      every pathogen. In addition, while vaccine-resistant bacteria have never been
      reported, accumulating literature is providing evidence that vaccination can
      reduce the raise of antibiotic resistant strains by decreasing their use.

PMID- 22981393
TI  - Uniportal endoscopic gastrocnemius recession for treatment of gastrocnemius
      equinus with a dedicated EGR system with retractable blade.
AB  - This study examined the effectiveness and safety of a uniportal endoscopic
      gastrocnemius recession with a specifically designed uniportal endoscopic system.
      Fifty-three patients underwent 60 endoscopic gastrocnemius recessions. Their mean
      range of ankle dorsiflexion changed from a preoperative value of -2.9 degrees  +/
      1.9 degrees  to a postoperative value of 12.8 degrees  +/- 1.7 degrees , for a
      total increase of 15.7 degrees  +/- 1.8 degrees  of ankle dorsiflexion (p <
      .001). The average time from skin incision to closure was 4 minutes and 19 +/-
      33.6 seconds. Overall, 4 (6.67%) cases (procedures) were associated with a
      complication, including 1 (1.67%) case of triceps surae weakness that resolved
      after physical therapy. Three (5%) cases developed nerve complications, with 2
      (3.33%) cases of transient neuritis that spontaneously resolved at 5 and 8 weeks
      postoperatively, respectively, and 1 (1.67%) that experienced persistent
      cutaneous anesthesia in the distribution of the sural nerve along the lateral
      aspect of the foot up to 4 months postoperatively. There were no cases of wound
      dehiscence or delayed healing, painful scar formation, infection at the surgical
      site, hematoma, or deep venous thrombosis. Endoscopic gastrocnemius recession
      with a uniportal system appears to be safe and effective.

PMID- 22981394
TI  - Plant science: the key to preventing slow cadmium poisoning.
AB  - Practically all human populations are environmentally exposed to cadmium (Cd),
      mostly through plant-derived food. A growing body of epidemiological evidence
      suggests that there is no margin of safety between current Cd exposure levels and
      the threshold for adverse health effects and, hence, there is an urgent need to
      lower human Cd intake. Here we review recent studies on rice (Oryza sativa) and
      Cd-hyperaccumulating plants that have led to important insights into the
      processes controlling the passage of Cd from the soil to edible plant organs. The
      emerging molecular understanding of Cd uptake, root retention, root-to-shoot
      translocation and grain loading will enable the development of low Cd
      accumulating crops.

PMID- 22981395
TI  - Plastid non-coding RNAs: emerging candidates for gene regulation.
AB  - Recent advances in transcriptomics and bioinformatics, specifically strand
      specific RNA sequencing, have allowed high-throughput, comprehensive detection of
      low-abundance transcripts typical of the non-coding RNAs studied in bacteria and
      eukaryotes. Before this, few plastid non-coding RNAs (pncRNAs) had been
      identified, and even fewer had been investigated for any functional role in gene
      regulation. Relaxed plastid transcription initiation and termination result in
      full transcription of both chloroplast DNA strands. Following this, post
      transcriptional processing produces a pool of metastable RNA species, including
      distinct pncRNAs. Here we review pncRNA biogenesis and possible functionality,
      and speculate that this RNA class may have an underappreciated role in plastid
      gene regulation.

PMID- 22981396
TI  - The relationship between plasma aluminum content, lymphocyte DNA damage, and
      oxidative status in persons using aluminum containers and utensils daily.
AB  - OBJECTIVES: The aim of this study was to explore the in vivo effect of the plasma
      aluminum content on lymphocyte DNA damage, the plasma protein carbonyl (PC)
      content, and malondialdehyde (MDA) and total antioxidative capacity (TAC) levels
      in aluminum exposed and non-exposed humans. DESIGN AND METHODS: Peripheral blood
      samples were collected from in vivo aluminum exposed and non-exposed humans and
      the above parameters were measured. RESULTS: The mean values of lymphocyte DNA
      damage, plasma MDA, PC levels, and aluminum concentrations were found to be
      significantly higher in the aluminum exposed group than within the control group
      (p<0.01). On the other hand, plasma TAC levels were found to be significantly
      lower in the aluminum exposed group than in the control group (p<0.001).
      Significant positive correlations were found to exist between lymphocyte DNA
      damage and the aluminum concentration (r=0.643, p<0.001), DNA damage and MDA
      (r=0.491, p<0.001), and DNA damage and PC (r=0.548, p<0.01). A negative
      correlation was found between TAC and DNA damage (r=-0.600 p<0.001) in the
      aluminum exposed group. CONCLUSION: Findings from the study revealed that an
      increased plasma aluminum concentration was associated with increased oxidative
      stress and increased DNA damage in aluminum exposed humans.

PMID- 22981397
TI  - Vitamin B(12) in type 2 diabetic patients treated with metformin.
AB  - OBJECTIVE: To test vitamin B12 plasma levels in type 2 diabetic patients treated
      with metformin in our area. METHODS: A cross-sectional, observational study of
      consecutive type 2 diabetic patients on drug treatment attending an internal
      medicine outpatient clinic. RESULTS: One hundred and nine patients (81 treated
      with metformin) were enrolled into the study. Mean time on metformin treatment
      was 43.5 months and mean drug dose was 1,779 mg/day. Patients treated with
      metformin had significantly lower vitamin B(12) plasma levels (393.5 vs. 509
      pg/mL, P = .0008). Seven (8.6%) of 81 patients treated with metformin and none of
      the 28 patients not treated with the drug had vitamin B(12) plasma levels lower
      than 197 pg/mL. No correlation was found between vitamin B12 plasma levles and
      metformin treatment time or dosage. CONCLUSIONS: In type 2 diabetic patients,
      treatment with metformin is associated to lower vitamin B12 plasma levels.
      Vitamin B12 deficiency associated with metformin is relatively common in our
      area.

PMID- 22981398
TI  - Intraocular schwannoma.
AB  - Schwannoma is a proliferation of neoplastic Schwann cells. Whereas schwannomas of
      the head and neck region are common, intraocular tissues are rarely affected.
      Uveal schwannoma has been aptly called a "pseudomelanoma", reflecting the
      difficulty in its clinical distinction from uveal malignant melanoma. Most of our
      current knowledge on intraocular schwannoma is limited to case reports, short
      case series, and non-comprehensive literature reviews. Three isolated reports of
      uveal schwannoma with extrascleral extension exist in literature, but the
      prognostic significance of this growth pattern is unknown. We present a patient
      with choroidal schwannoma with extrascleral extension and review 46 previously
      reported cases of uveal schwannomas to delineate clinical and pathologic
      characteristics of these intraocular tumors with a specific emphasis on
      schwannoma with extraocular extension.

PMID- 22981399
TI  - Capillary versus arterial blood glucose testing in the operating room.

PMID- 22981401
TI  - Both NMDA and non-NMDA receptors mediate glutamate stimulation induced cofilin
      rod formation in cultured hippocampal neurons.
AB  - Cofilin is the major actin-depolymerizing factor in the CNS for the regulation of
      actin dynamics. Neurodegenerative stimuli can induce the formation of cofilin
      rod, a pathological structure composed of cofilin and actin. The formation of
      cofilin rod was found to disrupt synapse function and cause neurite loss. The aim
      of the present study is to study the whole process of cofilin rod formation
      pattern in cultured hippocampal neurons under excitotoxic stimulation and to
      explore its underlying pharmacological mechanism. By using live cell imaging of
      neurons overexpressing EGFP-tagged wild type cofilin, we found a two-phase
      pattern of rod formation induced by glutamate stimulation. The early phase of rod
      formation occurred shortly after stimulation (~0.5h) but quickly dissolved within
      2h. The second phase happened within a much longer time window, 8h after
      stimulation. Immunostaining of endogenous cofilin in neurons also confirmed this
      glutamate stimulation induced two-phase rod formation pattern. The first phase
      was co-related with intracellular calcium concentration and pH increase while the
      second phase was not. These two phases of cofilin rod formation induced by
      glutamate stimulation was antagonized by both non-NMDA and NMDA receptor
      antagonist DNQX and AP5, respectively. Our results for the first time demonstrate
      the dynamic cofilin rod formation pattern under stress stimulation in detail by
      time lapse imaging. These findings reveal a novel time course of excitotoxicity
      induced neuronal damage and indicate a potential target of neuropathy treatment
      of neurodegenerative diseases.

PMID- 22981400
TI  - Top-down approach to vestibular compensation: translational lessons from
      vestibular rehabilitation.
AB  - This review examines vestibular compensation and vestibular rehabilitation from a
      unified translational research perspective. Laboratory studies illustrate
      neurobiological principles of vestibular compensation at the molecular, cellular
      and systems levels in animal models that inform vestibular rehabilitation
      practice. However, basic research has been hampered by an emphasis on
      'naturalistic' recovery, with time after insult and drug interventions as primary
      dependent variables. The vestibular rehabilitation literature, on the other hand,
      provides information on how the degree of compensation can be shaped by specific
      activity regimens. The milestones of the early spontaneous static compensation
      mark the re-establishment of static gaze stability, which provides a common
      coordinate frame for the brain to interpret residual vestibular information in
      the context of visual, somatosensory and visceral signals that convey
      gravitoinertial information. Stabilization of the head orientation and the eye
      orientation (suppression of spontaneous nystagmus) appear to be necessary by not
      sufficient conditions for successful rehabilitation, and define a baseline for
      initiating retraining. The lessons from vestibular rehabilitation in animal
      models offer the possibility of shaping the recovery trajectory to identify
      molecular and genetic factors that can improve vestibular compensation.

PMID- 22981402
TI  - Naringenin and quercetin reverse the effect of hypobaric hypoxia and elicit
      neuroprotective response in the murine model.
AB  - Exposure to high-altitude results in hypobaric hypoxia which is considered as an
      acute physiological stress. This condition often leads to high-altitude illnesses
      such as high-altitude cerebral edema, high altitude pulmonary edema and hypoxic
      muscle weakness. Hypoxic injuries can be prevented by either preconditioning with
      cobalt chloride or treatment with drugs. The aim of current investigation was to
      evaluate the effect of naringenin (NGEN) and quercetin (QUR) against behavioral
      impairment and neuronal damage in hypoxia induced murine model. An oral
      administration of NGEN or QUR (10mg/kg each) was given to the animal prior to
      every hypoxic treatment. Behavioral changes were evaluated along with the hypoxia
      exposure for all the groups. After hypoxia exposure and drug administration, the
      mice were euthanized; brains were harvested and stored for further analysis.
      Expressions of hypoxia induced proteins were ensured by Western blotting. Our
      results demonstrate expression of hypoxia inducible factor 1alpha (HIF1alpha),
      vascular endothelial growth factor (VEGF), active caspase 3 and ubiquitin levels
      were significantly reduced upon drug treatment. However, expressions of
      chaperones (Hsp70, Hsp90 and C-terminus Hsp70 interacting protein) were
      moderately changed. We established our findings based on behavioral test,
      hematoxylin and eosin as well as amino-cupric silver stainings. In addition, the
      protective nature of these drugs was corroborated with immunoblot and
      immunofluorescence results, where we confirmed the down regulation of caspase 3
      and ubiquitinated proteins. To conclude, treatment with NGEN and QUR alone
      substantially ameliorated hypoxia induced brain dysfunction and acts like a
      neuroprotectant.

PMID- 22981403
TI  - Beneficial effects of sulindac in focal cerebral ischemia: a positive role in
      Wnt/beta-catenin pathway.
AB  - BACKGROUND: Accumulated evidences have established that inflammatory damage plays
      an important role in cerebral ischemic pathogenesis and may represent a target
      for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug.
      However, little is known regarding the effect of sulindac in acute cerebral
      ischemia. Here, we designed this study to investigate the potential protective
      effects of sulindac in focal cerebral ischemia and the mechanisms underlying in
      vivo. METHODS: Focal cerebral ischemia was induced in male Sprague-Dawley rats by
      permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at
      dose of 4, 10, or 20mg/kg at 30 min before the operation. Neurological deficit
      scores, brain water content and infarct volumes were measured at 24h after pMCAO.
      Immunohistochemistry, western blot and reverse transcription-polymerase chain
      reaction were used for examining the mediators involved in Wnt/beta-catenin
      signaling pathway, including the positive regulators dishevelled (Dvl) and beta
      catenin, the negative regulators adenomatous polyposis coli (APC), and P-beta
      catenin, as well as the downstream targets Bcl-2, Bax and claudin-5. RESULTS:
      Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits,
      brain water content and infarct volumes. The same dose of sulindac upregulated
      the expression of Dvl, beta-catenin, Bcl2 and claudin-5, and downregulated APC, P
      beta-catenin and Bax compared with Vehicle group. CONCLUSIONS: These results
      showed that sulindac had a significant beneficial effect in cerebral ischemia;
      this effect may be correlated with the activation of the Wnt/beta-catenin
      signaling.

PMID- 22981404
TI  - Caregiver assistance among Medicare beneficiaries with atrial fibrillation and
      factors associated with anticoagulant treatment.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac
      arrhythmia and disproportionately affects the elderly. OBJECTIVE: This study
      describes patient characteristics and caregiver assistance among Medicare
      beneficiaries with AF and examines factors associated with receiving
      anticoagulant treatment. METHODS: Patients with AF and age/gender-matched
      controls were identified from Medicare Current Beneficiary Survey data from 2001
      to 2006. A logistic regression model was used to assess factors associated with
      receiving anticoagulants in a subgroup of patients with AF whose treatment
      pattern was established for 2 consecutive years. Sample weights were applied to
      obtain nationally representative estimates. RESULTS: A total of 2990 patients
      with AF and 5980 control patients were included in the burden of disease
      analysis, and 1481 patients with AF were included in the anticoagulant predictor
      analysis. Patients with AF had a higher level of comorbidity (Charlson
      Comorbidity Index: 3.3 vs 1.5; P < 0.05), worse self-perceived health status (P <
      0.001), and greater level of disability (P < 0.001) than their matched
      counterparts. A greater proportion of patients with AF required caregiver
      assistance (62.8% vs 51.5%; P < 0.001). Logistic regression found that higher
      Charlson Comorbidity Index scores, difficulty in obtaining necessary health care,
      older age, being widowed, a history of psychiatric disorders, and being
      underweight decreased the likelihood of receiving anticoagulant therapy.
      CONCLUSIONS: In a Medicare population, a greater need for caregiver assistance
      was observed in patients with AF. Subgroups characterized by frailty or inability
      for self-care were identified as being less likely to receive anticoagulant
      therapy. The need for caregiver assistance among patients with AF, as well as the
      patient subgroups identified as less likely to receive anticoagulant therapy,
      should be considered when making treatment decisions.

PMID- 22981405
TI  - The role of protein-bound uremic toxins on peripheral artery disease and vascular
      access failure in patients on hemodialysis.
AB  - OBJECTIVE: p-Cresyl sulfate (PCS) and indoxyl sulfate (IS) have been reported to
      predict poor clinical outcomes in hemodialysis (HD) patients. However, little is
      known about the effect of the two toxins on peripheral arterial disease (PAD) and
      vascular access dysfunction. Our objective was to explore the association between
      the two toxins and PAD and vascular access failure (VAF) in a hemodialysis-based
      cohort. METHODS: We enrolled 100 stable and eligible HD patients from a single
      medical center. These patients were screened for PAD by machine and recorded as
      ABI (ankle brachial index) and brachial-ankle PWV (pulse wave velocity). Serum
      levels of PCS, IS and biochemical data were also collected concurrently. In
      addition, we also recorded the first event of VAF and frequency of PTA and
      thrombectomy during 3-year follow-up. RESULTS: Total and free PCS were correlated
      to right and left ABI and PWV (p < 0.01), and total IS was associated with right
      and left ABI (p < 0.01) by Pearson's analysis. Repeated measuring by mixed model
      analysis revealed that serum albumin (p = 0.003), cholesterol (p = 0.01) and
      total PCS (p = 0.031) had significant correlation with ABI after adjusting other
      confounding factors. As for brachial-ankle PWV, serum triglyceride (p = 0.002),
      total IS (p = 0.04) and total PCS (p = 0.050) reached significance finally. In
      addition, multivariate Cox regression analysis revealed dialysis length and total
      PCS were related to AV-shunt failure event (Hazard Ratio: 1.14, p = 0.01, and
      Hazard Ratio: 1.04, p = 0.04, respectively). Both of total and free PCS and IS
      were also positively linked to numbers of PTA and thrombectomy. Further, the
      Kaplan-Meier analysis showed only total PCS was significantly associated with
      vascular access failure event (log rank P = 0.02). CONCLUSION: This study shows
      that the serum levels of PCS and IS were associated with PAD and total PCS could
      be a valuable determinant of access viability other than traditional or
      nontraditional risk factors in HD patients.

PMID- 22981407
TI  - Comparison of parasite-specific immunoglobulin levels in two chicken lines during
      sustained infection with Ascaridia galli.
AB  - Increasingly large numbers of poultry are held in production systems with access
      to outdoor areas. In these systems intestinal helminths are found with flock
      prevalences of up to 100%. Helminth infections influence chicken health
      negatively, which is why the following investigation has been performed. In the
      present experiment, 20 chickens of two inbred chicken lines containing the major
      histocompatibility complex (MHC) haplotypes, B14 and R5, were inoculated with 500
      embryonated Ascaridia galli eggs. The A. galli-specific IgG titres of serum
      samples and the excretion of A. galli eggs in chicken faeces were measured for a
      period of 81 weeks. The level of excreted A. galli eggs measured as eggs per gram
      chicken faeces (EPG) varied greatly between chickens in each line. Significant
      differences were found between the two lines and with the R5 chickens reaching
      the highest levels. Likewise, the A. galli-specific IgG titres in serum differed
      significantly between the two lines, and an inverse relationship between
      infection level (EPG) and antibody titres was found. Although this inverse
      relationship suggests that humoral immunity may be involved in protection against
      A. galli infection, the high antibody titres did not prevent continued infection.

PMID- 22981406
TI  - Statins use and coronary artery plaque composition: results from the
      International Multicenter CONFIRM Registry.
AB  - OBJECTIVE: The effect of statins on coronary artery plaque features beyond
      stenosis severity is not known. Coronary CT angiography (CCTA) is a novel non
      invasive method that permits direct visualization of coronary atherosclerotic
      features, including plaque composition. We evaluated the association of statin
      use to coronary plaque composition type in patients without known coronary artery
      disease (CAD) undergoing CCTA. METHODS: From consecutive individuals, we
      identified 6673 individuals (2413 on statin therapy and 4260 not on statin
      therapy) with no known CAD and available statin use status. We studied the
      relationship between statin use and the presence and extent of specific plaque
      composition types, which was graded as non-calcified (NCP), mixed (MP), or
      calcified (CP) plaque. RESULTS: The mean age was 59 +/- 11 (55% male). Compared
      to the individuals not taking statins, those taking statins had higher prevalence
      of risk factors and obstructive CAD. In multivariable analyses, statin use was
      associated with increased the presence of MP [odds ratio (OR) 1.46, 95%
      confidence interval (CI) 1.27-1.68), p < 0.001] and CP (OR 1.54, 95% CI 1.36
      1.74, p < 0.001), but not NCP (OR 1.11, 95% CI 0.96-1.29, p = 0.1). Further, in
      multivariable analyses, statin use was associated with increasing numbers of
      coronary segments possessing MP (OR 1.52, 95% CI 1.34-1.73, p < 0.001) and CP (OR
      1.52, 95% CI 1.36-1.70, p < 0.001), but not coronary segments with NCP (OR 1.09,
      95% CI 0.94-1.25, p = 0.2). CONCLUSION: Statin use is associated with an
      increased prevalence and extent of coronary plaques possessing calcium. The
      longitudinal effect of statins on coronary plaque composition warrants further
      investigation.

PMID- 22981408
TI  - [Vitamin D supplementation: A iatrogenic hypercalcemia concerning an HIV-infected
      patient with disseminated tuberculosis].

PMID- 22981409
TI  - Risk models for mortality following elective open and endovascular abdominal
      aortic aneurysm repair: a single institution experience.
AB  - OBJECTIVES: To develop and validate an "in house" risk model for predicting
      perioperative mortality following elective AAA repair and to compare this with
      other models. DESIGN: Multivariate logistics regression analysis was used to
      identify risk factors for perioperative-day mortality from one tertiary
      institution's prospectively maintained database. MATERIALS AND METHODS:
      Consecutive elective open (564) and endovascular (589) AAA repairs (2000-2010)
      were split randomly into development (810) and validation (343) data sets. The
      resultant model was compared to Glasgow Aneurysm Score (GAS), Modified Customised
      Probability Index (m-CPI), CPI, the Vascular Governance North West (VGNW) model
      and the Medicare model. RESULTS: Variables associated with perioperative
      mortality included: increasing age (P = 0.034), myocardial infarct within last 10
      years (P = 0.0008), raised serum creatinine (P = 0.005) and open surgery (P =
      0.0001). The areas under the receiver operating characteristic curve (AUC) for
      predicted probability of 30-day mortality in development and validation data sets
      were 0.79 and 0.82 respectively. AUCs for GAS, m-CPI and CPI were poor (0.63,
      0.58 and 0.58 respectively), whilst VGNW and Medicare model were fair (0.73 and
      0.79 respectively). CONCLUSIONS: In this study, an "in-house" developed and
      validated risk model has the most accurate discriminative value in predicting
      perioperative mortality after elective AAA repair. For purposes of comparative
      audit with case mix adjustments, national models such as the VGNW or Medicare
      models should be used.

PMID- 22981410
TI  - Detection of odorant molecules via surface acoustic wave biosensor array based on
      odorant-binding proteins.
AB  - In this paper, we present an array of biosensors for vapour phase detection of
      odorant molecules based on surface acoustic wave (SAW) resonators coated with
      odorant-binding proteins (OBPs). For the first time, the sensing capabilities of
      three different OBPs, as sensitive layers for SAW devices, are studied and
      compared. The SAW biosensor array is composed of three SAW devices coated by the
      droplet method with the wild-type OBP from cow (wtbOBP), a double mutant of the
      OBP from cow (dmbOBP) and the wild-type OBP from pig (wtpOBP). An uncoated device
      is used to compensate the variations of the environmental parameters. The SAW
      devices consist of two-port resonators fabricated on quartz (ST-cut, x
      propagation) with electrodes made of aluminium covered with a thin gold film (2
      nm thick). The obtained surface densities of OBP layers are between 1.18*10(-6)
      kg/m(2) and 2.31*10(-6) kg/m(2) and were calculated measuring the resonant
      frequency shift of the SAW devices after the coating. The SAW biosensor array was
      tested in nitrogen upon exposure to vapours of R-(-)-1-octen-3-ol (octenol), in
      the range of concentration between 13 and 61 ppm, and R-(-)-carvone (carvone), in
      the range between 9 and 80 ppm. The highest sensitivity for detection of octenol
      (25.9 Hz/ppm) was obtained using the wtpOBP-based SAW biosensor, while the
      highest sensitivity for detection of carvone (9.2 Hz/ppm) was obtained using the
      dmbOBP-based SAW biosensor.

PMID- 22981411
TI  - A modular cell-based biosensor using engineered genetic logic circuits to detect
      and integrate multiple environmental signals.
AB  - Cells perceive a wide variety of cellular and environmental signals, which are
      often processed combinatorially to generate particular phenotypic responses.
      Here, we employ both single and mixed cell type populations, pre-programmed with
      engineered modular cell signalling and sensing circuits, as processing units to
      detect and integrate multiple environmental signals. Based on an engineered
      modular genetic AND logic gate, we report the construction of a set of scalable
      synthetic microbe-based biosensors comprising exchangeable sensory, signal
      processing and actuation modules. These cellular biosensors were engineered using
      distinct signalling sensory modules to precisely identify various chemical
      signals, and combinations thereof, with a quantitative fluorescent output. The
      genetic logic gate used can function as a biological filter and an amplifier to
      enhance the sensing selectivity and sensitivity of cell-based biosensors. In
      particular, an Escherichia coli consortium-based biosensor has been constructed
      that can detect and integrate three environmental signals (arsenic, mercury and
      copper ion levels) via either its native two-component signal transduction
      pathways or synthetic signalling sensors derived from other bacteria in
      combination with a cell-cell communication module. We demonstrate how a modular
      cell-based biosensor can be engineered predictably using exchangeable synthetic
      gene circuit modules to sense and integrate multiple-input signals. This study
      illustrates some of the key practical design principles required for the future
      application of these biosensors in broad environmental and healthcare areas.

PMID- 22981412
TI  - Intermolecular G-quadruplex structure-based fluorescent DNA detection system.
AB  - Adopting multi-donors to pair with one acceptor could improve the performance of
      fluorogenic detection probes. However, common dyes (e.g., fluorescein) in close
      proximity to each other would self-quench the fluorescence, and the fluorescence
      is difficult to restore. In this contribution, we constructed a novel "multi
      donors-to-one acceptor" fluorescent DNA detection system by means of the
      intermolecular G-quadruplex (IGQ) structure-based fluorescence signal enhancement
      combined with the hairpin oligonucleotide. The novel IGQ-hairpin system was
      characterized using the p53 gene as the model target DNA. The proposed system
      showed an improved assay performance due to the introduction of IGQ-structure
      into fluorescent signaling probes, which could inhibit the background
      fluorescence and increase fluorescence restoration amplitude of fluoresceins upon
      target DNA hybridization. The proof-of-concept scheme is expected to provide new
      insight into the potential of G-quadruplex structure and promote the application
      of fluorescent oligonucleotide probes in fundamental research, diagnosis, and
      treatment of genetic diseases.

PMID- 22981413
TI  - Highly sensitive and selective chemiluminescent imaging for DNA detection by
      ligation-mediated rolling circle amplified synthesis of DNAzyme.
AB  - A highly sensitive DNA biosensing method down to sub-femtomolar level with
      excellent selectivity was proposed by designing an amplified synthesis of
      horseradish peroxidase mimicking DNAzyme and introducing the amplified DNAzyme to
      chemiluminescent (CL) imaging. The amplified synthesis was achieved by combining
      a target DNA related ligase reaction with rolling circle amplification (RCA),
      which produced thousands of repeated sequences to bind hemin and form a mass of
      horseradish peroxidase-mimicing DNAzyme units. The amplification strategy greatly
      enhanced the CL emission of the luminol-H(2)O(2) system. The genotyping method
      displayed highly specific biochemistry in allele discrimination. The novel CL
      imaging strategy based on ligation-mediated RCA synthesis of DNAzyme showed high
      fidelity in discriminating single-base mismatch and efficiently facilitated
      signal amplification for sensitive target DNA detection. It could detect DNA
      ranging from 1*10(-15) M to 1*10(-11) M with a detection limit of 0.26 fM. The
      proposed approach provided a robust, cost-efficient, highly sensitive and
      specific platform for genetic target analysis in bioanalysis and clinic
      biomedical application.

PMID- 22981415
TI  - Development of the dorsal ramus of the spinal nerve in the chick embryo: a close
      relationship between development and expression of guidance cues.
AB  - The spinal nerve, which is composed of dorsal root ganglion (DRG) axons and
      spinal motor axons, divides into ventral and dorsal rami. Although the
      development of the ventral ramus has been examined in considerable detail, that
      of the dorsal ramus has not. Therefore, we first examined the spatial-temporal
      pattern of the dorsal ramus formation in the chick embryo, with special reference
      to the projection to the dermamyotome and its derivatives. Next, we focused on
      two guidance molecules, chick semaphorin 3A (SEMA3A) and fibroblast growth factor
      8 (FGF8), because these are the best candidates as molecules for controlling the
      dorsal ramus formation. Using in situ hybridization and immunohistochemistry
      methods, we clearly showed a close relationship between the spatial-temporal
      expression of SEMA3A/FGF8 and the projection of dorsal ramus fibers to the dorsal
      muscles. We further examined the axonal response of motor and DRG neurons to
      SEMA3A and FGF8. We showed that motor axons responded to both SEMA3A-induced
      repulsion and FGF8-induced attraction. On the other hand, DRG axons responded to
      SEMA3A-induced repulsion but not to FGF8-induced attraction. These findings
      suggest that FGF8-induced attraction may guide early motor axons beneath the
      myotome and that SEMA3A-induced repulsion may prevent these early motor axons
      from entering the myotome. Our results also imply that the loss of SEMA3A
      expression in the dorsal muscles may lead to the gross projection of the dorsal
      ramus fibers into the dorsal muscles. Together, SEMA3A and FGF8 may contribute to
      the proper formation of the dorsal ramus.

PMID- 22981414
TI  - Maternal intake of Omega-3 essential fatty acids improves long term potentiation
      in the dentate gyrus and Morris water maze performance in rats.
AB  - Omega-3 fatty acid deprivation during development reduces performance in learning
      tasks, and dietary DHA supplementation improves learning ability and enhances
      long term memory in both young and old animals. However, little attention has
      been paid to the effect of maternal intake of Omega-3 fatty acids on hippocampal
      function in their pups. Randomly some of the pregnant dams were supplemented with
      Omega-3 essential fatty acid, others with tap-water, during pregnancy and breast
      feeding by gavage daily. Spatial learning and memory was tested in Morris water
      maze. Field potentials from the dentate gyrus were recorded in response to medial
      perforant pathway in urethane-anesthetized pups. Omega-3-treated rats found the
      platform less traveled and closer to platform than control animals. However the
      pups from both groups show the same performance in retrieval task. No differences
      were found between corresponding animal groups in the input-output curves of the
      field potential slopes, suggesting no effect of Omega-3 supplementation on basal
      synaptic efficacy. Potentiation of population spike amplitude was much higher in
      pups of Omega-3 treated dams than control. Up to now Omega 3 fatty acid has been
      shown to be beneficial on the synaptic plasticity only under some pathological
      conditions. For the first time, we showed improved dentate gyrus-LTP and enhanced
      Morris water maze performance in healthy pups from healthy dams treated with
      Omega-3 fatty acids during pregnancy and breast-feeding period. Molecular studies
      are needed to explain Omega-3 effect on hippocampal synaptic plasticity.

PMID- 22981416
TI  - Cerebral antioxidant enzyme increase associated with learning deficit in type 2
      diabetes rats.
AB  - In this study, we examined alterations in the enzymatic antioxidant defenses
      associated with learning deficits induced by type 2 diabetes, and studied the
      effects of the peroxisome proliferator-activated receptor gamma agonist
      pioglitazone on these learning deficits. Learning ability was assessed by visual
      discrimination tasks in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a
      model of spontaneous type 2 diabetes. Levels of the antioxidant enzymes
      glutathione peroxidase (GPx), Cu(2+)-Zn(2+) superoxide dismutase (CuZn-SOD) and
      manganese SOD were measured in the cortex, hippocampus and striatum. Half the
      rats received oral pioglitazone (20mg/kg/day) from the early stage of diabetes
      (22 weeks old) to 27 weeks old. OLETF rats showed learning deficits compared with
      control, Long-Evans Tokushima Otsuka (LETO) rats. GPx levels in the cortex and
      hippocampus were increased in OLETF rats compared with LETO rats, with an inverse
      correlation between GPx in the hippocampus and learning score. CuZn-SOD levels
      were also increased in the hippocampus in OLETF rats. Pioglitazone reduced blood
      glucose and increased serum adiponectin levels, but had no effect on learning
      tasks or antioxidant enzymes, except for CuZn-SOD. These results suggest that an
      oxidative imbalance reflected by increased brain antioxidant enzymes plays an
      important role in the development of learning deficits in type 2 diabetes. Early
      pioglitazone administration partly ameliorated diabetic symptoms, but was unable
      to completely recover cerebral oxidative imbalance and functions. These results
      suggest that diabetes-induced brain impairment, which results in learning
      deficits, may have occurred before the appearance of the symptoms of overt
      diabetes.

PMID- 22981417
TI  - Straub tail reaction in mice treated with sigma(1) receptor antagonist in
      combination with methamphetamine.
AB  - Straub tail reaction (STR) was observed in male ddY mice after simultaneous
      administration with BMY 14802 (a non-specific sigma receptor antagonist) and
      methamphetamine (METH). The intensity and duration of STR depended on the dose of
      BMY 14802. The tail reaction was inhibited completely by (+)-SKF 10,047 (a
      putative sigma(1) receptor agonist) and partially by PB 28 (a putative sigma(2)
      receptor agonist). The STR was mimicked in mice treated with BD 1047 (a putative
      sigma(1) receptor antagonist), but not SM-21, a putative sigma(2) receptor
      antagonist, in combination with METH. STR evoked with BD 1047 plus METH was
      inhibited by (+)-SKF 10,047. STR induced by BMY 14802 and METH was abolished by
      naloxone (a relatively non-selective opioid receptor antagonist) or U-50,488H (a
      selective kappa-agonist), suggesting that the STR may be mediated by activation
      of opioid receptor system.

PMID- 22981418
TI  - Factors associated to experienced continuity of care between primary and
      outpatient secondary care in the Catalan public healthcare system.
AB  - OBJECTIVE: To analyze patient's reported elements of relational, informational
      and managerial (dis)continuity between primary and outpatient secondary care and
      to identify associated factors. METHODS: Cross-sectional study by means of a
      survey of a random sample of 1500 patients attended in primary and secondary care
      for the same condition. The study settings consisted of three health areas of the
      Catalan health system. Data were collected in 2010 using the CCAENA
      questionnaire, which identifies patients' experiences of continuity of care.
      Descriptive analyses and multivariable logistic regression models were carried
      out. RESULTS: Elements of continuity of care were experienced by most patients.
      However, elements of discontinuity were also identified: 20% and 15% were seen by
      more than one primary or secondary care physician, respectively. Their secondary
      care physician or both professionals were identified as responsible for their
      care by 40% and 45% of users, respectively. Approximately 20% reported a lack of
      information transfer. Finally, 72% of secondary care consultations were due to
      primary care referral, whilst only 36% reported a referral back to primary care.
      Associated factors were healthcare setting, age, sex, perceived health status and
      disease duration. CONCLUSION: Users generally reported continuity of care,
      although elements of discontinuity were also identified, which can be partially
      explained by the healthcare setting and some individual factors. Elements of
      discontinuity should be addressed to better adapt care to patients' needs.

PMID- 22981420
TI  - Elder abuse in the emergency department.
AB  - Elder abuse is an important challenge in global societies. Detection of and
      intervention in elder abuse is crucial to the well-being of older people. Older
      people are high consumers of health care services and the consequences of elder
      abuse may provide a catalyst to attendance in the emergency department. This
      paper considers the topic of elder abuse and examines issues pertaining to
      understandings, recognition, screening and care in the emergency department
      environment.

PMID- 22981419
TI  - nSTAT: open-source neural spike train analysis toolbox for Matlab.
AB  - Over the last decade there has been a tremendous advance in the analytical tools
      available to neuroscientists to understand and model neural function. In
      particular, the point process - generalized linear model (PP-GLM) framework has
      been applied successfully to problems ranging from neuro-endocrine physiology to
      neural decoding. However, the lack of freely distributed software implementations
      of published PP-GLM algorithms together with problem-specific modifications
      required for their use, limit wide application of these techniques. In an effort
      to make existing PP-GLM methods more accessible to the neuroscience community, we
      have developed nSTAT--an open source neural spike train analysis toolbox for
      Matlab(r). By adopting an object-oriented programming (OOP) approach, nSTAT
      allows users to easily manipulate data by performing operations on objects that
      have an intuitive connection to the experiment (spike trains, covariates, etc.),
      rather than by dealing with data in vector/matrix form. The algorithms
      implemented within nSTAT address a number of common problems including
      computation of peri-stimulus time histograms, quantification of the temporal
      response properties of neurons, and characterization of neural plasticity within
      and across trials. nSTAT provides a starting point for exploratory data analysis,
      allows for simple and systematic building and testing of point process models,
      and for decoding of stimulus variables based on point process models of neural
      function. By providing an open-source toolbox, we hope to establish a platform
      that can be easily used, modified, and extended by the scientific community to
      address limitations of current techniques and to extend available techniques to
      more complex problems.

PMID- 22981421
TI  - Innovative ED older persons' care: a report on an initiative developed in
      Southampton Hospital ED.
AB  - This paper reports on the development of an innovative project-the Older Persons'
      Outreach and Support Team' (OPOST) - within University Hospital of Southampton's
      Emergency Department. The achievements of this Team are benchmarked against the
      'quality, innovation, productivity, prevention' (QIPP) agenda. The demographic
      changes resulting in the UK's ageing patient population are also discussed in
      this context.

PMID- 22981422
TI  - Hyponatremia in older adults presenting to the emergency department.
AB  - Hyponatremia is a common disorder seen in the emergency department and is more
      prevalent in older adults than in other adult populations (Miller, 2009). Though
      often discovered by accident, through routine bloodwork, even mild hyponatremia
      has been shown to have potentially dangerous consequences for older adults,
      increasing their risks for falls, altered mental status, osteoporosis and
      fractures, and gastrointestinal disturbances (Soiza and Talbot, 2011). Optimal
      management of older adults with hyponatremia in the ED involves not only
      treatment of serum sodium levels and the immediate consequence of the disorder,
      but exploration and reversal of the causes of the hyponatremia to avoid
      recurrence. This case study illustrates the clinical presentation, complications
      and management of hyponatremia in the setting of the emergency department.

PMID- 22981423
TI  - Emerging airway smooth muscle targets to treat asthma.
AB  - Asthma is characterized in part by variable airflow obstruction and non-specific
      hyperresponsiveness to a variety of bronchoconstrictors, both of which are
      mediated by the airway smooth muscle (ASM). The ASM is also involved in the
      airway inflammation and airway wall remodeling observed in asthma. For all these
      reasons, the ASM provides an important target for the treatment of asthma.
      Several classes of drugs were developed decades ago which targeted the ASM -
      including beta-agonists, anti-cholinergics, anti-histamines and anti-leukotrienes
      - but no substantially new class of drug has appeared recently. In this review,
      we summarize the on-going work of several laboratories aimed at producing novel
      targets and/or tools for the treatment of asthma. These range from receptors and
      ion channels on the ASM plasmalemma, to intracellular effectors (particularly
      those related to cyclic nucleotide signaling, calcium-homeostasis and
      phosphorylation cascades), to anti-IgE therapy and outright destruction of the
      ASM itself.

PMID- 22981424
TI  - Salivary cortisol and immunoglobulin A: responses to stress as predictors of
      health complaints reported by caregivers of offspring with autistic spectrum
      disorder.
AB  - In the caregiving model of chronic stress, few studies have been conducted with
      young middle-aged samples and no data exists about acute stress response in this
      population. To extend knowledge in this issue, health complaints and
      psychological, endocrine, and immunological responses to stress have been
      assessed in a cross-sectional sample of 41 parents of offspring with autistic
      spectrum disorder (ASD) in comparison with 37 non-caregiver parents. Salivary
      cortisol and immunoglobulin A (IgA) levels were measured before, during, and
      after a mental psychosocial stressor, while mood and state anxiety were evaluated
      before and after the stress. Health complaints, personality traits, socio
      economic status, and characteristics of the care recipient were assessed.
      Caregivers reported more health complaints showing buffered cortisol and IgA
      responses and greater increases in fatigue to acute stress than the controls. In
      terms of predictive power of health complaints, IgA levels, care status, and
      severity of the care recipient are especially relevant for caregivers. Results
      strongly suggest a dysregulation in the immune and hormonal stress-induced
      responses in middle-aged caregivers, with immune component and care
      characteristics as the main modulators of health complaints. A deficit in the
      adaptive capability of stress response is plausible in this population,
      emphasizing the need to consider family approaches when planning protocols for
      assistance to ASD patients.

PMID- 22981425
TI  - Burden of allergic rhinitis: allergies in America, Latin America, and Asia
      Pacific adult surveys.
AB  - Allergic rhinitis (AR; also nasal allergies or "hay fever") is a chronic upper
      airway inflammatory disease that affects ~60 million adults and children in the
      United States. The duration and severity of AR symptoms contribute to a
      substantial burden on patients' quality  of life (QoL), sleep, work productivity,
      and activity. This study was designed to examine symptoms, QoL, productivity,
      comorbidities, disease management, and pharmacologic treatment of AR in United
      States and ex-U.S. sufferers. Allergies in America was a comprehensive telephone
      based survey  of 2500 adults with AR. These data are compared and contrasted with
      findings from the Pediatric Allergies in America, Allergies in Latin America, and
      Allergies in Asia-Pacific telephone surveys. The prevalence of physician
      diagnosed AR was 14% in U.S. adults, 7% in Latin America adults, and  9% in Asia
      Pacific adults. Nasal congestion is the most common and bothersome symptom for
      adults. Approximately two-thirds of adults rely on medication to relieve
      intolerable AR symptoms. Incomplete relief, slow onset, <24-hour relief, and
      reduced efficacy with sustained use were commonly  reported with AR medications,
      including intranasal corticosteroids. One in seven U.S. adults reported achieving
      little to no relief with AR medications. Bothersome adverse effects of AR
      medications included drowsiness, a drying feeling, medication dripping down the
      throat, and bad taste. Perception  of inadequate efficacy was the leading cause
      of medication discontinuation or change and contributed to treatment
      dissatisfaction. These findings support the assertion that AR burden has been
      substantially underestimated and identify several important challenges to
      successful management of  AR.

PMID- 22981427
TI  - Plants and pathogens: putting infection strategies and defence mechanisms on the
      map.
AB  - All plant organs are vulnerable to colonisation and molecular manipulation by
      microbes. When this interaction allows proliferation of the microbe at the
      expense of the host, the microbe can be described as a pathogen. In our attempts
      to understand the full nature of the interactions that occur between a potential
      pathogen and its host, various aspects of the molecular mechanisms of infection
      and defence have begun to be characterised. There is significant variation in
      these mechanisms. While previous research has examined plant-pathogen
      interactions with whole plant/organ resolution, the specificity of infection
      strategies and changes in both gene expression and protein localisation of immune
      receptors upon infection suggest there is much to be gained from examination of
      plant-microbe interactions at the cellular level.

PMID- 22981428
TI  - Supervised quality assessment of medical image registration: application to intra
      patient CT lung registration.
AB  - A novel method for automatic quality assessment of medical image registration is
      presented. The method is based on supervised learning of local alignment
      patterns, which are captured by statistical image features at distinctive
      landmark points. A two-stage classifier cascade, employing an optimal multi
      feature model, classifies local alignments into three quality categories:
      correct, poor or wrong alignment. We establish a reference registration error set
      as basis for training and testing of the method. It consists of image
      registrations obtained from different non-rigid registration algorithms and
      manually established point correspondences of automatically determined landmarks.
      We employ a set of different classifiers and evaluate the performance of the
      proposed image features based on the classification performance of corresponding
      single-feature classifiers. Feature selection is conducted to find an optimal
      subset of image features and the resulting multi-feature model is validated
      against the set of single-feature classifiers. We consider the setup generic,
      however, its application is demonstrated on 51 CT follow-up scan pairs of the
      lung. On this data, the proposed method performs with an overall classification
      accuracy of 90%.

PMID- 22981429
TI  - 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside ameliorates vascular
      senescence and improves blood flow involving a mechanism of p53 deacetylation.
AB  - BACKGROUND AND AIMS: 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside (THSG), a
      resveratrol analog with glucoside, has been shown in various studies to inhibit
      proliferation of vascular smooth muscle cells, attenuate inflammation, and
      prevent vascular endothelial dysfunction. In the study, we examined the effects
      of THSG on vascular senescence and blood flow. METHODS AND RESULTS: Oral
      administration of THSG for 14 weeks, resulted in notable increases in blood flow
      in spontaneously hypertensive rats (SHRs); and effective inhibition of vascular
      senescence as indicated by senescence-associated beta-galactosidase (SA-beta-gal)
      staining, phosphorylation of gammaH2AX observed by stain analysis of
      immunofluorescence, and K373 acetylation of p53 in the aortic arches of SHRs.
      Oral administration of THSG also induced eNOS expression and urinary NOx
      production. THSG weekly activated SIRT1 activity, stimulated eNOS promoter
      reporter gene activity, and ameliorated H(2)O(2)-induced cellular senescence and
      K373 acetylation of p53 in cultured human umbilical vein endothelial cells
      (HUVECs). CONCLUSIONS: THSG improves blood flow and ameliorates vascular
      senescence by increasing eNOS expression and Sirt1 activity and decreasing
      acetylation of p53 at K373 site, at least in part, both in vitro and in vivo.

PMID- 22981426
TI  - Neurometabolites in schizophrenia and bipolar disorder - a systematic review and
      meta-analysis.
AB  - This meta-analysis evaluates alterations of neurometabolites in schizophrenia and
      bipolar disorder. PubMed was searched to find controlled studies evaluating N
      acetylaspartate (NAA), Choline (Cho) and Creatine (Cr) assessed with ((1))H-MRS
      (proton magnetic resonance spectroscopy) in patients with schizophrenia and
      bipolar disorder up to September 2010. Random effects meta-analyses were
      conducted to estimate pooled standardized mean differences. The statistic was
      used to quantify inconsistencies. Subgroup analyses were conducted to explore
      potential explanations for inconsistencies. The systematic review included 146
      studies with 5643 participants. NAA levels were affected in schizophrenia and
      bipolar disorder. Decreased levels in the basal ganglia and frontal lobe were the
      most consistent findings in schizophrenia; decreased levels in the basal ganglia
      were the most consistent findings in bipolar disorder. Cho and Cr levels were not
      altered in either disorder. Findings for Cr were most consistent in the thalamus,
      frontal lobe and dorsolateral prefrontal cortex in schizophrenia and the basal
      ganglia and frontal lobe in bipolar disorder. Findings for Cho were most
      consistent in the thalamus, frontal lobe and anterior cingulate cortex in
      schizophrenia and basal ganglia in bipolar disorder. Large, carefully designed
      studies are needed to better estimate the extent of alterations in
      neurometabolites.

PMID- 22981430
TI  - Endogenous sex hormones impact the progression of subclinical atherosclerosis in
      women during the menopausal transition.
AB  - OBJECTIVE: To determine whether endogenous sex hormones (estradiol (E2),
      testosterone (T), sex hormone binding globulin (SHBG), and follicle stimulating
      hormone (FSH)) are longitudinally associated with progression of atherosclerosis
      among women at midlife. METHODS: 249 Pre- or early peri-menopausal women (42-57
      years) from the Study of Women's Health Across the Nation (SWAN) were followed
      for up to 9 years (median = 3.7 years) and had up to 5 repeated measures of
      common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear
      mixed models were used for statistical analysis. Final models included age at
      baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI,
      insulin resistance index, lipids, C-reactive protein and co-morbidity. RESULTS:
      In final models for IMT, each one log unit decrease in SHBG was associated with a
      0.005 mm/year increase in IMT progression (P = 0.003). E2, T, and FSH were not
      associated with level or progression of IMT. For AD, each one log unit decrease
      in E2 was associated with a 0.012 mm/year increase in AD progression (P = 0.04)
      and each one log unit increase in FSH was associated with a 0.016 mm/year
      increase in AD progression (P = 0.003). T and SHBG were not associated with
      progression or level of AD. CONCLUSIONS: Independent of SBP, BMI, lipids and
      other covariates, lower E2 and SHBG, and higher FSH were associated with
      increased subclinical atherosclerosis progression in women at midlife.

PMID- 22981432
TI  - A systematic review: treatment and prognosis of patients with fibrolamellar
      hepatocellular carcinoma.
AB  - BACKGROUND: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver
      tumor presenting earlier in life than nonfibrolamellar hepatocellular carcinoma
      (NFL-HCC), with distinct epidemiologic and clinical characteristics. Although FLC
      is believed to have a better prognosis than NFL-HCC, data on treatment and
      prognosis are scarce. We performed a systematic review to investigate treatment
      options and clinical outcomes of patients with FLC. STUDY DESIGN: The study is a
      systematic review of the literature and pooled analysis of individual patient
      data. RESULTS: A total of 35 series were analyzed, reporting on 575 patients (52%
      female, elevated alpha-fetoprotein in 10%, cirrhosis in 3%, hepatitis B in 2%),
      most of whom were treated with partial hepatectomy (55%) or orthotopic liver
      transplantation (23%). Nineteen studies provided data on 206 individual patients
      with a median age of 21 years and tumor size of 12 cm. Median overall survival
      (OS) was 39 months; 1-year, 3-year, and 5-year OS rates were 85%, 53%, and 44%,
      respectively. For patients treated with liver resection, median OS was 18.5 years
      and 1-year, 3-year, and 5-year OS were 93%, 80%, and 70%, respectively. Based on
      data from 15 studies, FLC appeared to follow a relatively indolent course
      compared with NFL-HCC. CONCLUSIONS: Patients with FLC treated with partial
      hepatectomy have excellent long-term survival, with 5-year overall survival
      reaching 70%. Patients fared worse with the use of other therapeutic options
      including chemotherapy, intra-arterial therapy, and transplantation, although
      data directly comparing resection vs transplantation were limited.

PMID- 22981431
TI  - Protective role of clusterin in preserving endothelial function in AL
      amyloidosis.
AB  - Misfolded immunoglobulin light chain proteins (LC) in light chain amyloidosis
      (AL) are toxic to vascular tissues. We tested the hypothesis that chaperone
      protein clusterin preserves endothelial function and cell survival during LC
      exposure. METHODS: LC (20 MUg/mL) were given to human aortic endothelial cells
      (EC) for 24-h and clusterin protein/gene expression and secretion were measured.
      DNA fragmentation was measured with/without recombinant clusterin (Clu, 300
      ng/mL). Adipose arterioles (non-AL subjects) were tested for dilator responses to
      acetylcholine/papaverine at baseline and after 1-h of LC +/- Clu. RESULTS: LC
      reduced EC clusterin secretion, protein and gene expression while increasing DNA
      fragmentation. Clu attenuated LC-induced DNA fragmentation and restored dilator
      response to acetylcholine (logEC50: control -7.05 +/- 0.2, LC + Clu -6.53 +/-
      0.4, LC -4.28 +/- 0.7, p < 0.05 versus control, LC + Clu). CONCLUSIONS: LC
      induced endothelial cell death and dysfunction while reducing clusterin
      protein/gene expression and secretion. Exogenous clusterin attenuated LC
      toxicity. This represents a new pathobiologic mechanism and therapeutic target
      for AL amyloidosis.

PMID- 22981433
TI  - A histopathologic basis for surgical debridement to promote healing of venous
      ulcers.
AB  - BACKGROUND: Pathologic analysis of deep tissue obtained during debridement of
      venous ulcers is often unnoticed in its importance. We previously reported
      pathologic findings on 139 patients with venous ulcers. The objective of this
      study was to correlate the pathologic findings in venous ulcers with wound
      healing to establish a negative margin for debridement. STUDY DESIGN: Consecutive
      patients with a lower extremity venous ulcer present for at least 4 weeks,
      presenting to a single wound healing center, were included. Wounds underwent
      aggressive surgical debridement beyond the subcutaneous level until judged to
      have a viable base. Specimens were scored based on cellularity, vascularity,
      collagen composition, inflammation, and dense fibrosis, with a highest possible
      score of 13. Healing was the primary outcome for analysis. RESULTS: Of the 26
      patients who met inclusion criteria, only 50% of them (13 patients) with a total
      of 18 venous ulcers underwent surgical debridement available for pathologic
      analysis. Mean ulcer area was 34.7 cm(2) at initial presentation, and 89% of
      patients had a continuous positive healing curve as measured by decreasing wound
      area (from 34.7 cm(2) to 14.3 cm(2)). However, specimens with dense fibrosis,
      decreased cellularity, mature collagen, and pathology score less than 10 were
      predominantly nonhealing ulcers. CONCLUSIONS: Presence of dense fibrosis and high
      levels of mature collagen in deep tissue specimens are significant correlative
      factors in nonhealing of venous ulcers. We recommend deep debridement on all
      venous ulcers that are refractory to healing until the level of absence of dense
      fibrosis and mature collagen is reached to promote venous ulcer healing.

PMID- 22981434
TI  - Dissociation of porcine reproductive and respiratory syndrome virus
      neutralization from antibodies specific to major envelope protein surface
      epitopes.
AB  - Glycoprotein 5 (GP5) and membrane (M) protein are the major proteins in the
      envelope of porcine reproductive and respiratory syndrome virus (PRRSV). Although
      viral neutralization epitopes are reported in GP5 and M of type 2 PRRSV, their
      significance as targets of porcine humoral immunity is not well described. Thus,
      we constructed recombinant polypeptides containing ectodomain neutralization
      epitopes to examine their involvement in porcine antibody neutralization and
      antiviral immunity. PRRSV infection elicited ectodomain-specific antibodies,
      whose titers did not correlate with the neutralizing antibody (NA) response.
      Ectodomain-specific antibodies from PRRSV-neutralizing serum bound virus but did
      not neutralize infectivity. Furthermore, immunization of pigs with ectodomain
      polypeptides raised specific antibodies and provided partial protection without a
      detectable NA response. Finally the polypeptides did not block infection of
      porcine macrophages. These results suggest that the GP5/M ectodomain peptide
      epitopes are accessible for host antibody recognition, but are not associated
      with antibody-mediated virus neutralization.

PMID- 22981435
TI  - Targeted integration of a rAAV vector into the AAVS1 region.
AB  - Adeno-associated virus (AAV) has been reported to integrate in a site-specific
      manner into chromosome 19 (a site designated AAVS1), a phenomenon that could be
      exploited for ex vivo targeted gene therapy. Recent studies employing LM-PCR to
      determine AAV integration loci; however, have, contrary to previous results with
      less reliable methods, concluded that the proclivity for AAV integration at AAVS1
      is minimal. We tested this conclusion employing LM-PCR protocols designed to
      avoid bias. Hep G2 cells were infected with rAAV2-GFP and coinfected with wt AAV2
      to supply Rep in trans. Sorted cells were cloned and cultured. In 26 clones that
      retained fluorescence, DNA was extracted and AAV-genomic junctions amplified by
      two LM-PCR methods. Sequencing was performed without bacterial cloning. Of these
      26 clones it was possible to assign a genomic integration site to 14, of which 9
      were in the AAVS1 region. In three additional clones, rAAV integration junction
      were to an integrated wt AAV genome while two were to an rAAV genome. We also
      show that integration of the AAV-GFP genome can be achieved without cointegration
      of the AAV genome. Based on the pattern of integrants we propose, for potential
      use in ex vivo targeted gene therapy, a simplified PCR method to identify clones
      that have rAAV genomes integrated into AAVS1.

PMID- 22981436
TI  - Computer simulation of the activity of the elderly person living independently in
      a Health Smart Home.
AB  - We propose a simulator of human activities collected with presence sensors in our
      experimental Health Smart Home "Habitat Intelligent pour la Sante (HIS)". We
      recorded 1492 days of data on several experimental HIS during the French national
      project "AILISA". On these real data, we built a mathematical model of the
      behavior of the data series, based on "Hidden Markov Models" (HMM). The model is
      then played on a computer to produce simulated data series with added flexibility
      to adjust the parameters in various scenarios. We also tested several methods to
      measure the similarity between our real and simulated data. Our simulator can
      produce large data base which can be further used to evaluate the algorithms to
      raise an alarm in case of loss in autonomy.

PMID- 22981437
TI  - Effects of 4,4'-dichloro-diphenyl diselenide (ClPhSe)2 on toxicity induced by
      mercuric chloride in mice: a comparative study with diphenyl diselenide (PhSe)2.
AB  - The effects of 4,4'-dichloro-diphenyl diselenide (ClPhSe)(2) on the toxicity
      induced by mercuric chloride (HgCl(2)) were investigated and compared with
      diphenyl diselenide (PhSe)(2). Mice received HgCl(2) for three days and, on the
      third day, received (PhSe)(2) or (ClPhSe)(2). The results verified that the
      administration of (ClPhSe)(2) in mice exposed to HgCl(2) increased renal delta
      aminolevulinate dehydratase (delta-ALA-D), Na(+), K(+)-ATPase activities and non
      protein thiol (NPSH) levels and also decreased thiobarbituric acid-reactive
      substances (TBARS) and ascorbic acid levels, when compared to mice exposed to
      HgCl(2)+(PhSe)(2). Plasma and urinary protein, hemoglobin and hematocrit levels
      and histological parameters were also ameliorated in mice exposed to
      HgCl(2)+(ClPhSe)(2). In addition, the hepatic damage in mice exposed to
      HgCl(2)+(PhSe)(2) was reduced in animals exposed to (ClPhSe)(2). To sum up, the
      introduction of a functional group (chloro) in the aromatic ring of diaryl
      diselenide reduced the toxicity of this compound in liver and kidney of mice
      exposed to HgCl(2).

PMID- 22981438
TI  - SDS3 interacts with ARNT in an AhR ligand-specific manner regulating expression
      of cKrox and S100A4 in CD4+CD8+ DPK thymocytes differentiation.
AB  - To study mechanisms underlying differential effects of 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) and benzo(a)pyrene (B(a)P) on thymocyte differentiation, we
      examined effects of AhR ligands on the differentiation of DPK cells, a
      CD4(+)CD8(+) thymic lymphoma cell line which can differentiate into CD4(+)CD8(-)
      thymocytes. In contrast to TCDD, which inhibited the differentiation, B(a)P
      showed little effect. Antigen-mediated up-regulation of S100A4, S100A6, galectin
      1, and TRAF5-like protein was remarkably suppressed by TCDD, but slightly by
      B(a)P. Immunoprecipitation using anti-ARNT Ab revealed that SDS3, a component of
      the Sin3/HDAC repressor complex, was associated with ARNT only when DPK cells
      were incubated with TCDD. Expression of cKrox S100A4 was derepressed when SDS3
      protein was reduced. These results indicate that although it is generally known
      that many AhR ligands such as TCDD and B(a)P function mainly by the AhR/ARNT
      complex, ligand-specific interaction between SDS3 and ARNT exerts differential
      effects on the expression of genes associated with thymocyte differentiation.

PMID- 22981439
TI  - A simple controller for the prediction of three-dimensional gait.
AB  - The objective of this study is to investigate the potential of forward dynamic
      modeling in predicting the functional outcome of complicated orthopedic
      procedures involving relocation or removal of muscles or correction osteotomies
      in the lower extremities. For this purpose, we developed a torque actuated
      forward dynamics based three-dimensional model of gait, that extends the previous
      reported work of Van der Kooij et al. (2003). The mechanical properties are
      scaled to the subject and lateral stability is provided by an 'offset plus
      proportional' controller (Hof, 2008). Kinematic constraints are formulated based
      on three independent gait descriptors and implemented in an optimization
      algorithm. The computational effort is small (1min per gait cycle on a 1GHz
      processor) and the control scheme generates symmetric and cyclic gait based on
      the desired gait descriptors. An interface with the inverse dynamics based
      AnyBody Modeling System, a musculoskeletal modeling tool, provides insight in
      muscle activities. The proposed control scheme is robust against mediolateral
      perturbations. The predictive capacity of the model is evaluated by simulating
      pathological gait by means of weakening the hip abductors, and the model is able
      to predict some of the trends of compensatory strategies in such a perturbed
      mechanical system.

PMID- 22981440
TI  - Quantification of red blood cell deformation at high-hematocrit blood flow in
      microvessels.
AB  - The deformation of red blood cells in microvessels was investigated numerically
      for various vessel diameters, hematocrits, and shear rates. We simulated blood
      flow in circular channels with diameters ranging from 9 to 50 MUm, hematocrits
      from 20% to 45%, and shear rates from 20 to 150 s(-1) using a particle-based
      model with parallel computing. The apparent viscosity predicted by the simulation
      was in good agreement with previous experimental results. We quantified the
      deformation of red blood cells as a function of radial position. The numerical
      results demonstrated that because of the shape transition in response to local
      shear stress and the wall effect, the radial variation of red blood cell
      deformation in relatively large microvessels could be classified into three
      different regions: near-center, middle, and near-wall regions. Effects of the
      local shear stress and wall varied with vessel diameter, hematocrit, and shear
      rate.

PMID- 22981441
TI  - [Carcinoid heart - case report].
AB  - We describe the case of a 76-year-old woman, diagnosed with a neuroendocrine
      tumor of the cecum in 2004, with liver metastases and carcinoid syndrome since
      September 2010. The patient had been treated intermittently with chemotherapy
      cycles, and remained symptomatic, with worsening secondary lesions. In June 2011
      she began to present signs and symptoms of right heart failure and was
      hospitalized in September 2011. Transthoracic two- and three-dimensional
      echocardiography revealed enlarged right atrium and ventricle and thickened and
      fixed tricuspid and pulmonary valve leaflets, causing severe tricuspid
      regurgitation and mild pulmonary regurgitation and stenosis, suggestive of
      carcinoid heart disease. The authors discuss the clinical importance of
      transthoracic echocardiography, and the more recent three-dimensional
      echocardiography, as the diagnostic exam of choice in these cases, as it is
      especially suitable for assessing the valves and subvalvular apparatus.

PMID- 22981442
TI  - Drop of residual plasmatic activity of ADAMTS13 to undetectable levels during
      acute disease in a patient with adult-onset congenital thrombotic
      thrombocytopenic purpura.

PMID- 22981443
TI  - Type 3 hereditary hemochromatosis in a patient from sub-Saharan Africa: is there
      a link between African iron overload and TFR2 dysfunction?

PMID- 22981444
TI  - Impact of patient selection, disease progression, and adverse events on
      esophageal cancer outcomes after trimodality therapy.
AB  - BACKGROUND: Neoadjuvant chemoradiation followed by surgery (NeoCRT) has been
      advocated as standard therapy for resectable esophageal cancer. Our objective was
      to compare oncologic outcomes between NeoCRT and upfront surgical resection
      (SURG). METHODS: We conducted a single-institution, retrospective review of all
      potentially resectable esophageal cancer patients treated with NeoCRT or SURG.
      RESULTS: From 2003 to 2010, 151 patients had NeoCRT (n = 48; 31.8%) or SURG (n =
      103; 68.1%). Histology was mostly adenocarcinoma (77.5%) or squamous carcinoma
      (19.2%). Mean radiation dose was 44 +/- 0.1 Gy, and 80.8% received platinum-based
      doublet chemotherapy. There were more women in the SURG group (23.3% vs 4.2%; p <
      0.01) and more cardiovascular comorbidity in the NeoCRT group (39.6% vs 21.4%; p
      = 0.027). There was no difference in age, histology, R0 resection rate, and
      treatment-related mortality (NeoCRT = 4.2%; SURG = 3.9%; p = 0.15). Failure to
      undergo resection after NeoCRT (n = 11; 22.9%) was mainly due to disease
      progression (n = 6) or treatment-related mortality (n = 4). Resection could not
      be performed in 4 SURG patients (3.9%; p < 0.001; unresectable = 2; occult
      metastases = 2). NeoCRT did not improve median survival (NeoCRT = 29 +/- 6; SURG
      = 26 +/- 3 months; p = 0.376) or recurrence-free interval (NeoCRT = 25.8 +/- 5;
      SURG = 19.4 +/- 2 months; p = 0.19). Complete pathologic response (n = 8; 21.6%)
      was not associated with improved survival. If we exclude from analysis NeoCRT
      patients who did not undergo surgery, survival was significantly improved after
      NeoCRT (NeoCRT = 41 +/- 15; SURG = 24 +/- 8 months; p = 0.0082). CONCLUSIONS:
      Patient selection and early assessment of treatment response may be key factors
      in identifying the best candidates for trimodality therapy.

PMID- 22981445
TI  - Solanaceae-free diet for scar pruritus.

PMID- 22981446
TI  - Computed tomography osteoabsorptiometry for assessing the density distribution of
      subchondral bone as a measure of long-term mechanical stress in the "rugby
      shoulder".
AB  - BACKGROUND: Rugby is a collision sport with a high risk of shoulder injury.
      Although traumatic anterior shoulder instability is common, the long-term effects
      of rugby and joint instability on the shoulder have not been described; thus,
      this study assessed the effects of rugby itself, and joint instability, on the
      glenoid cavity. MATERIALS AND METHODS: Both sides of the shoulders from 25 rugby
      players and 17 control patients with unilateral shoulder instability were
      prospectively evaluated by means of computed tomography osteoabsorptiometry,
      which represents the distribution of mineralization in subchondral bone plate
      (DMSB) as a marker of the long-term loading history of a joint. For the
      quantitative analysis, intergroup differences of maximum Hounsfield unit (HU)
      values in 7 areas on the glenoid were assessed in the uninjured intact shoulder
      to characterize the influence of rugby. Side-to-side differences of the HUs in
      each area were assessed in each participant to characterize the effects of
      shoulder instability. For the qualitative analysis, associations between the
      patterns of each DMSB and each group were assessed by means of correspondence
      analysis. RESULTS: All examined areas on the glenoid had a significantly higher
      HUs in rugby players. Shoulder instability affected the HUs in both groups. A
      qualitative analysis demonstrated that the maximum HU tended to be shifted more
      inferiorly in rugby players and in the unstable shoulders. CONCLUSIONS: Rugby
      affects the shoulder joint, regardless of any history of instability, suggesting
      that "rugby shoulder" tends to involve degenerative changes, such as
      osteoarthritis or labral tears.

PMID- 22981447
TI  - Propionibacterium acnes: an underestimated etiology in the pathogenesis of
      osteoarthritis?
AB  - BACKGROUND: Propionibacterium acnes is a common pathogen in infections after
      shoulder surgery. Recent reports found positive P acnes cultures in a high
      percentage of patients who had revision shoulder arthroplasty for "aseptic
      loosening" without any overt signs of infection. Isolation of P acnes is
      difficult, and by use of conventional microbiological protocols of 48-hour
      incubation, a considerable proportion of patients with possible P acnes infection
      may remain unidentified. We recently noted P acnes in shoulder joint cultures in
      patients undergoing primary shoulder replacement for glenohumeral arthropathy
      without any signs of infection. METHODS: We collected aspirates and biopsy
      specimens from 55 consecutive patients with arthritic shoulders undergoing
      primary joint replacement and examined them for the presence of P acnes. Special
      measures were taken to ensure that the specimens were carefully taken from within
      the joint to reduce the risk of contamination to minimal. RESULTS: In 23 of 55
      consecutive patients (41.8%) undergoing primary shoulder joint replacement, P
      acnes was found in the joint fluid and tissues taken before the insertion of the
      implants. All these patients were treated early postoperatively with pathogen
      directed specific dual oral antibiotic treatment for 4 weeks. In none have any
      signs of infection developed. DISCUSSION AND CONCLUSION: This finding of a high
      incidence of P acnes in joints before arthroplasty may suggest a role of P acnes
      in the pathogenesis of glenohumeral arthropathy. In addition, it raises the
      question of whether development of painful joint replacement later on and
      presumed aseptic loosening do, in fact, comprise an unrecognized low-grade
      infection that has been present since before the index operation.

PMID- 22981448
TI  - Clinical meaning of unexpected positive cultures (UPC) in revision shoulder
      arthroplasty.
AB  - PURPOSE: This study analyzed the prevalence and clinical meaning of unexpected
      positive cultures (UPCs) in revision shoulder arthroplasty for causes different
      than infection. METHODS: Between 1976 and 2007, 107 consecutive patients with
      UPCs, no previous suspicion of infection, and fulfilling inclusion criteria were
      identified. Forty-five partial (PSA) and 62 total shoulder arthroplasties (TSA)
      with different preoperative diagnoses were reviewed. Cases were classified as
      true infections, possible infections, contaminants, and undetermined. Mean follow
      up was 5.6 +/- 5.3 years. RESULTS: The prevalence of UPC was 15%. Male sex was a
      risk factor for UPC. Results of preoperative blood tests and intraoperative
      pathology were negative in 94 and 97 cases, respectively. Most prevalent bacteria
      were Propionibacterium acnes (n = 68) and Staphylococcus epidermidis (n = 21).
      Fifty-three patients received treatment with antibiotics and 54 did not. In 11
      patients, a postoperative arthroplasty infection during follow-up was diagnosed
      by culture and was produced by the same microorganism as the one isolated on the
      UPC (true infection). Risk factors for true infection vs contamination included
      revision of a TSA vs a PSA and the number of previous surgeries. Antibiotic use
      and number of positive cultures did not influence the rate of true infections.
      CONCLUSIONS: UPCs are a prevalent condition in revision shoulder arthroplasty for
      causes different than infection. In at least 25% of cases, UPC had no clinical
      relevance. In 10% of cases, a persistent infection was demonstrated.

PMID- 22981449
TI  - Theophylline regulates inflammatory and neurotrophic factor signals in functional
      recovery after C2-hemisection in adult rats.
AB  - Recovery of respiratory activity in an upper cervical hemisection model (C2H) of
      spinal cord injury (SCI) can be induced by systemic theophylline administration
      24-48 h after injury. The objectives in the present study are (1) to identify pro
      inflammatory and neurotrophic factors expressed after C2H and (2) molecular
      signals involved in functional recovery. Four groups of adult female rats
      classified as (i) sham (SH) controls, (ii) subjected to a left C2 hemisection
      (C2H) only, (iii) C2H rats administered theophylline for 3 consecutive days 2
      days after C2H (C2H-T day 5) and (iv) C2H rats treated with theophylline for 3
      consecutive days 2 days after C2H and then weaned for 12 days (C2H-T day 17)
      prior to assessment of respiratory function and molecular analysis were employed.
      Corresponding sham controls, C2H untreated (vehicle only controls) and C2H
      treated (theophylline) rats were sacrificed, C3-C6 spinal cord segments quickly
      dissected and left (ipsilateral) hemi spinal cord and right (contralateral) hemi
      spinal cord were separately harvested 2 days post surgery. Sham operated and C2H
      untreated-controls corresponding to C2H-T day 5 and C2H-T day 17 rats,
      respectively, were prepared similarly. Messenger RNA levels for pro-inflammatory
      genes (TXNIP, IL-1beta, TNF-alpha and iNOS) and neurotrophic and survival factors
      (BDNF, GDNF, and Bcl2) were analyzed by real time quantitative PCR. Gene
      expression pattern was unaltered in SH rats. TXNIP, iNOS, BDNF, GDNF and Bcl2
      mRNA levels were significantly increased in the ipsilateral hemi spinal cord in
      C2H rats. BDNF, GDNF and Bcl2 levels remained elevated in the ipsilateral hemi
      spinal cord in C2H-T day 5 rats. In this same group, there was further
      enhancement in TXNIP and IL-1beta while iNOS returned to basal levels.
      Theophylline increased DNA binding activity of transcription factors - cyclic AMP
      responsive element (CRE) binding protein (CREB) and pro-inflammatory NF-kappaB.
      Messenger RNA levels for all genes returned to basal levels in C2H-T day 17 rats.
      However, BDNF mRNA levels remained significantly elevated after weaning from the
      drug. Our results suggest that enhanced resolution of early inflammatory
      processes and expression of pro-survival factors may underlie theophylline
      induced respiratory recovery. The results identify potential targets for gene and
      drug therapies.

PMID- 22981451
TI  - Modulating the modulators: interaction of brain norepinephrine and cannabinoids
      in stress.

PMID- 22981450
TI  - Cytokines that promote nerve regeneration.

PMID- 22981452
TI  - Increased glucose availability does not restore prolonged spreading depression
      durations in hypotensive rats without brain injury.
AB  - Maintenance of transmembrane ionic gradients and their restoration after cortical
      spreading depression (CSD) are energy dependent. We recently showed an inverse
      relationship between blood pressure and CSD duration that is independent of
      tissue oxygenation. Here, we tested the alternative hypothesis that glucose
      availability becomes rate-limiting for CSD recovery upon reduced blood pressure
      in anesthetized rats under full systemic physiological monitoring. Hypotension
      induced by controlled exsanguination significantly prolonged CSD durations,
      reduced propagation speeds, and diminished the blood flow response. Hyperglycemia
      failed to restore the prolonged CSD durations in hypotensive rats and did not
      significantly alter the propagation speed or the blood flow response. These data
      suggest that prolonged CSD durations during reduced cerebral perfusion pressure
      are independent of tissue energy status, and implicate alternative mechanisms of
      CSD recovery such as vascular clearance of extracellular K(+).

PMID- 22981454
TI  - Gait characteristics when walking with rounded soft sole shoes.

PMID- 22981453
TI  - Modulation of acetylcholine release by cholecystokinin in striatum: receptor
      specificity; role of dopaminergic neuronal activity.
AB  - Cholecystokinin, a neuroactive peptide functioning as a neurotransmitter and
      neuromodulator in the central nervous system, mediates a number of processes and
      is implicated in neurological and psychiatric disorders such as Parkinson's
      disease, anxiety and schizophrenia. Striatum is one of the brain structures with
      the highest concentrations of CCK in the brain, rich in CCK receptors as well.
      The physiological effect of CCK on cholinergic interneurons, which are the major
      interneurons in striatum and the modulatory interactions which exist between
      dopamine, acetylcholine and cholecystokinin in this brain structure are still
      unclear. We studied the effect of cholecystokinin octapeptide (CCK-8) on the
      release of acetylcholine (ACh) from striatal slices of the rat brain. CCK-8 (0.01
      0.1MUM) showed no statistically significant effect on the basal but enhanced dose
      dependently the electrically (2Hz)-evoked release of [(3)H]ACh. When slices were
      preperfused with 100MUM sulpiride, a selective dopamine D(2) receptor antagonist,
      the CCK-8 (0.01MUM) effect on electrically stimulated ACh release was increased
      nearly 2-fold. A similar increase was observed after depletion of endogenous
      dopamine (DA) from nigro-striatal dopaminergic neurons with 6-hydroxydopamine (6
      OHDA) (2* 250MUg/animal, i.c.v.). Furthermore in the presence of dopamine
      (100MUM) or apomorphine (10MUM), the prototypical DA receptor agonist, CCK-8
      (0.01MUM) failed to enhance the stimulation-evoked release of [(3)H]ACh. The D(2)
      receptor agonist quinpirol (1MUM) abolished the CCK-8 effect on electrically
      stimulated ACh release as well. The increase in electrically induced [(3)H]ACh
      release produced by 0.01MUM CCK-8 was antagonized by d,l loxiglumide (CR 1505),
      10MUM, a non-peptide CCK-A receptor antagonist and by Suc-Tyr-(OSO3)-Met-Gly-Trp
      Met-Asp-beta-phenethyl-amide (GE-410), 1MUM, a peptide CCK-A receptor antagonist.
      The antagonistic effect of GE-410 on the CCK-8-potentiated, electrically induced
      release of [(3)H]ACh was studied in striatum for the first time. CAM 1028
      (10MUM), a CCK-B receptor antagonist, also prevented the potentiating effect of
      CCK-8 (0.01MUM) on electrically stimulated release of [(3)H]ACh. The presented
      results indicate that (i) CCK-8 is capable of increasing ACh elicited by field
      electrical stimulation in striatum; (ii) CCK-8 is more effective in its ACh
      stimulating effect when dopaminergic activity in striatum is blocked i.e. CCK-8
      facilitated release of electrically induced ACh from cholinergic interneurons in
      the striatum is under the inhibitory control of the tonic activity of dopamine
      from the nigrostriatal pathway; (iii) the enhancing effect of CCK-8 on
      electrically evoked ACh release is mediated through both CCK-A and CCK-B
      cholecystokinin receptors located most likely on the cell bodies of cholinergic
      interneurons in striatum.

PMID- 22981455
TI  - Why the uptake of change and innovation is slow amongst the medical fraternity
      and how these can be overcome.

PMID- 22981456
TI  - Percutaneous transluminal septal myocardial ablation performed via the right
      coronary artery rather than the left anterior descending artery for the treatment
      of hypertrophic obstructive cardiomyopathy.

PMID- 22981457
TI  - Evaluation of normalization strategies for qPCR quantitation of intracellular
      viral DNA: the example of Vaccinia virus.
AB  - Quantitation of intracellular viral genomes is critical in both clinical and
      fundamental virology. Quantitative real time PCR (qPCR) is currently the gold
      standard to detect and monitor virus infections, due to its high sensitivity and
      reproducibility. The reliability of qPCR data depends primarily on the technical
      process. Normalization, which corrects inter-sample variations related to both
      pre-analytical and qPCR steps, is a key point of an accurate quantitation. Total
      DNA input and qPCR-measured standards were evaluated to normalize intracellular
      Vaccinia virus (VACV) genomes. Three qPCR assays targeting either a single-copy
      chromosomic gene, a repeated chromosomic DNA sequence, or a mitochondrial DNA
      sequence were compared. qPCR-measured standards, unlike total DNA input, allowed
      for accurate normalization of VACV genome, regardless of the cell number. Among
      PCR-measured standards, chromosomic DNA and mitochondrial DNA were equivalent to
      normalize VACV DNA and multi-copy standards displayed lower limits of
      quantitation than single-copy standards. The combination of two qPCR-measured
      standards slightly improved the reliability of the normalization. Using one or
      two multi-copy standards must be favored for relative quantitation of
      intracellular VACV DNA. This concept could be applied to other DNA viruses.

PMID- 22981458
TI  - Estimation of the sensitivity and specificity of assays for screening antibodies
      to HIV: a comparison between the frequentist and Bayesian approaches.
AB  - Bayesian and frequentist methods have been applied rarely to the same sets of
      data for evaluating assays for screening antibodies to HIV, especially for assays
      with relatively high sensitivities and/or specificities of 100% compared with
      reference assays. In this study, 95% confidence intervals and 95% Bayesian
      credible intervals were calculated for sensitivity and specificity for the
      evaluation of the accuracy of HIV antibody assays using data from China, WHO
      UNAIDS, USA, Australia, Tanzania, and India. When the sensitivity and/or
      specificity were 100%, a Bayesian approach obtained reasonable interval estimates
      of assays for screening antibodies to HIV, whereas frequentist methods express
      objectively the accuracy of each individual assay. It is suggested that the two
      types of estimates be reported simultaneously to evaluate more comprehensively a
      set of highly accurate antibodies for HIV assays.

PMID- 22981459
TI  - Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of
      nerve agent poisoning.
AB  - Potent organophosphorous (OP) agents, such as VX, are hazardous by absorption
      through the skin and are resistant to conventional pharmacological antidotal
      treatments. The residence time of a stoichiometric bioscavenger, human
      butyrylcholinesterase (huBuChE), in the plasma more closely matches that of VX
      than do the residence times of conventional therapy drugs (oxime, anti
      muscarinic, anticonvulsant). Intramuscular (i.m.) huBuChE afforded almost
      complete protection when administered prior to the onset of observable
      cholinergic signs of VX poisoning, but once signs of poisoning became evident the
      efficacy of i.m. huBuChE decreased. A combination of nerve agent therapy drugs
      (oxime, anti-muscarinic, anticonvulsant) with huBuChE (i.m.) protected 100% (8/8)
      of guinea-pigs from a lethal dose of VX (0.74 mg/kg) to 48 h, even when
      administered on signs of poisoning. Survival was presumed to be due to immediate
      alleviation of the cholinergic crisis by the conventional pharmacological
      treatment drugs, in conjunction with bioscavenger that prevented further absorbed
      agent reaching the AChE targets. Evidence to support this proposed mechanism of
      action was obtained from PKPD experiments in which multiple blood samples and
      microdialysate samples were collected from individual conscious ambulatory
      animals. Plasma concentrations of intramuscularly-administered atropine, diazepam
      and HI-6 reached a peak within 15 min and were eliminated rapidly within 4h.
      Plasma concentrations of huBuChE administered by the i.m. route took
      approximately 24h to reach a peak, but were well-maintained over the subsequent
      7days. Thus, the pharmacological therapy rapidly treated the initial signs of
      poisoning, whilst the bioscavenger provided prolonged protection by neutralising
      further nerve agent entering the bloodstream and preventing it from reaching the
      target organs.

PMID- 22981460
TI  - Physiologically based pharmacokinetic model for rats and mice orally exposed to
      chromium.
AB  - A multi-compartment physiologically based pharmacokinetic (PBPK) model was
      developed to describe the behavior of Cr(III) and Cr(VI) in rats and mice
      following long-term oral exposure. Model compartments were included for GI lumen,
      oral mucosa, forestomach/stomach, small intestinal mucosa (duodenum, jejunum,
      ileum), blood, liver, kidney, bone, and a combined compartment for remaining
      tissues. Data from ex vivo Cr(VI) reduction studies were used to characterize
      reduction of Cr(VI) in fed rodent stomach fluid as a second-order, pH-dependent
      process. For model development, tissue time-course data for total chromium were
      collected from rats and mice exposed to Cr(VI) in drinking water for 90 days at
      six concentrations ranging from 0.1 to 180 mg Cr(VI)/L. These data were used to
      supplement the tissue time-course data collected in other studies with oral
      administration of Cr(III) and Cr(VI), including that from recent NTP chronic
      bioassays. Clear species differences were identified for chromium delivery to the
      target tissue (small intestines), with higher concentrations achieved in mice
      than in rats, consistent with small intestinal tumor formation, which was
      observed upon chronic exposures in mice but not in rats. Erythrocyte:plasma
      chromium ratios suggest that Cr(VI) entered portal circulation at drinking water
      concentrations equal to and greater than 60 mg/L in rodents. Species differences
      are described for distribution of chromium to the liver and kidney, with
      liver:kidney ratios higher in mice than in rats. Overall, the PBPK model provides
      a good description of chromium toxicokinetics, with model predictions for tissue
      chromium within a factor of 3 for greater than 80% of measurements evaluated. The
      tissue data and PBPK model predictions indicate a concentration gradient in the
      small intestines (duodenum > jejunum > ileum), which will be useful for assessing
      the tumor response gradient observed in mouse small intestines in terms of target
      tissue dose. The rodent PBPK model presented here, when used in conjunction with
      a human PBPK model for Cr(VI), should provide a more robust characterization of
      species differences in toxicokinetic factors for assessing the potential risks
      associated with low-dose exposures of Cr(VI) in human populations.

PMID- 22981461
TI  - Process for purification of monoclonal antibody expressed in transgenic Lemna
      plant extract using dextran-coated charcoal and hexamer peptide affinity resin.
AB  - The production of therapeutic proteins using transgenic plants offers several
      advantages, including low production cost, absence of human pathogens, presence
      of glycosylation mechanisms, and the ability to fold complex therapeutic proteins
      into their proper conformation. However, impurities such as phenolic compounds
      and pigments encountered during purification are quite different from those faced
      during purification from mammalian cell culture supernatants. This paper deals
      with the development of a pretreatment and affinity separation process for the
      purification of a monoclonal antibody from transgenic Lemna plant extract. A
      pretreatment step is described using dextran-coated charcoal for the removal of
      pigments and phenolic compounds without reducing the antibody concentration.
      Then, the peptide affinity ligand HWRGWV coupled to a commercial polymethacrylate
      resin is used for the capture and purification of MAb from the pretreated plant
      extract. The final yield and purity of the MAb obtained were 90% and 96%
      respectively. The performance of the hexamer peptide resin after the pretreatment
      step was found to be similar to that obtained with a commercial Protein A resin.

PMID- 22981462
TI  - Coupling of microextraction by packed sorbents with gas chromatography with ionic
      liquid stationary phases for the determination of haloanisoles in wines.
AB  - A new method based on the coupling of microextraction by packed sorbents (MEPS)
      and gas chromatography with ionic liquid stationary phases for the determination
      of four haloanisoles in wine matrices is proposed. The analytes were concentrated
      in a C18 barrel insert and needle (BIN), desorbed with a small volume of an
      organic solvent, and determined by gas chromatography with electron-capture
      detection (GC-MUECD). The influence of several factors on the efficiency of
      extraction, washing and elution steps was investigated. Additionally, ionic
      liquid stationary phases of very different polarities were evaluated in terms of
      efficiency. Under optimized conditions, the analytes were first extracted in the
      sorbent material and, after an adequate washing step, eluted with 50 MUL of
      ethanol. An aliquot of 5 MUL of this extract was further injected, using a
      programmed temperature vaporizer (PTV), into the chromatographic system. The
      yield of the overall procedure ranged from 48 to 60%; the reproducibility of the
      method, calculated as the relative standard deviation (RSD), was below 10% for
      all compounds, and the limits of detection ranged from 1.2 to 4.8 ng L(-1).
      External calibration was used in the determination of the target compounds in
      wine samples.

PMID- 22981463
TI  - [Geophagia: progress toward understanding its causes and consequences].
AB  - Geophagia is an ancient practice subject to many prejudices. Recent animal
      experiments have shed light on its causes and consequences. Geophagia, a form of
      pica, may be induced by various factors. Clay, the material preferentially
      ingested by geophagic subjects, interacts with the food bolus and the digestive
      mucosa. Its capacity to form colloids and to adsorb and exchange ions results in
      both beneficial and harmful effects. In a less civilized age, the ingestion of
      clay may have reinforced digestive barriers against alkaloids and toxins,
      conferring a selective advantage on individuals practicing geophagia. However, in
      the modern Western world, complex interactions of clay with metals and ions are
      likely to generate low-level poisoning and deficiencies, potentially damaging the
      health of geophagic individuals and their offspring.

PMID- 22981464
TI  - [Unexplained paresthesias in a 28-year-old woman].

PMID- 22981465
TI  - Expression of metallothionein isoforms in peripheral blood leukocytes from Thai
      population residing in cadmium-contaminated areas.
AB  - Metallothionein (MT) is a group of proteins with high cadmium (Cd) affinity and
      with a potential role in Cd transportation and detoxification. The aim of the
      present study was to investigate the relationship between MT (MT-1A, MT-2A, and
      MT-3 isoforms) gene expression level in peripheral blood leukocytes and Cd
      associated renal injury in non-occupational exposed Thai population. The study
      was conducted in adult subjects residing in Cd-contaminated areas of Mae Sot
      District, Thailand. The basal levels of MT-1A, MT-2A, and MT-3 mRNA expression
      were determined in leukocytes by quantitative RT-PCR. MT-1A and MT-2A
      expressions, particularly MT-1A, were found to be significantly increased with
      elevated levels of blood and urinary Cd levels. In subjects with high urinary Cd
      levels, negative correlations between MT-1A and microalbumin, and between MT-2A
      and beta(2)-MG, were observed. These results suggest that MT gene expression may
      reflect susceptibility of the exposed population to Cd-induced renal dysfunction.
      MT-1A mRNA expression in leukocytes might be developed as a potential biomarker
      of Cd exposure and Cd-induced renal dysfunction.

PMID- 22981466
TI  - [Elderly severe chronic kidney disease patients: a difficult balance between
      benefits and risks].

PMID- 22981467
TI  - Purification and characterization of cellulase from North Pacific krill
      (Euphausia pacifica). Analysis of cleavage specificity of the enzyme.
AB  - Krill are filter feeders that consume algae, plankton and detritus, indicating
      that krill possess an adequate cellulose digesting system. However, less is known
      about the enzymatic properties of crustacean cellulases compared to termite
      cellulases. In the present study, 48 kDa-cellulase was highly purified from krill
      (Euphausia pacifica) in an effort to determine the cleavage specificity of the
      enzyme. The most notable characteristic of the enzyme was its high activity
      against both lichenan and carboxymethyl cellulose. The enzyme hydrolyzed internal
      beta-1,4 glycosidic bonds within lichenan as well as carboxymethyl cellulose to
      release oligosaccharides and glucose. The effects of pH and temperature on the
      activity and stability of both enzyme activities were almost identical. Cello
      oligosaccharides with a degree of polymerization of 4-6 were hydrolyzed by the
      enzyme, and the same endo-products, cellotriose, cellobiose and glucose, were
      produced from these oligosaccharides. Neither cellotriose nor cellobiose was
      hydrolyzed by the enzyme. The enzyme digested filter paper and sea lettuce to
      produce cellobiose, cellotriose and glucose as major products. Although amino
      acid sequence homology of the enzyme with termite cellulases and the presence of
      oligosaccharides in the enzyme suggested that the enzyme is produced by krill
      itself, further analysis is necessary.

PMID- 22981468
TI  - The intermediate disturbance hypothesis should be abandoned.
AB  - A leading idea about how disturbances and other environmental fluctuations affect
      species diversity is the intermediate disturbance hypothesis (IDH). The IDH
      states that diversity of competing species is, or should be expected to be,
      maximized at intermediate frequencies and/or intensities of disturbance or
      environmental change. I argue that the IDH has been refuted on both empirical and
      theoretical grounds, and so should be abandoned. Empirical studies only rarely
      find the predicted humped diversity-disturbance relationship. Theoretically, the
      three major mechanisms thought to produce humped diversity-disturbance
      relationships are logically invalid and do not actually predict what they are
      thought to predict. Disturbances and other environmental fluctuations can affect
      diversity, but for different reasons than are commonly recognized.

PMID- 22981469
TI  - Assessment of psychosocial risks faced by workers in Almeria-type greenhouses,
      using the Mini Psychosocial Factor method.
AB  - This work reports the use of the Mini Psychosocial Factor (MPF) method for
      assessing the psychosocial risks faced by agricultural workers in the greenhouses
      of Almeria (Spain) with the aim of improving their health. The variables Rhythm,
      Mobbing, Relationships, Health, Recognition, Autonomy, Emotional Involvement,
      Support, Compensation, Control, Demands, and Mental Load were recorded using a
      pre-validated questionnaire containing 15 questions. The sex, age, and
      nationality of the respondents (n = 310) were also recorded, as were the type of
      greenhouse in which each worked, the size of the greenhouse, and the crop grown.
      The results showed psychosocial risks to exist for the workers. Multiple
      correspondence analysis, however, showed that moderate risks can be offset by new
      prevention programmes that improve Spanish legislation in terms of workers'
      salaries, worker-employer social days, work timetables to facilitate family life,
      and training courses. This could improve the work environment and health of
      Almeria's greenhouse workers as well as their productivity.

PMID- 22981470
TI  - Muscle activation during the Pack Hike test and a critical wildfire fighting
      task.
AB  - The aim of this study was to examine the muscle activation of six global muscles
      during the successful completion of the Pack Hike test (PHT) and compare this to
      muscle activations during a critical wildfire fighting task. In-field surface
      electromyography was recorded from eight male wildfire fighters during the PHT
      and the rakehoe task - a critical wildfire suppression activity. All participants
      successfully completed the PHT within the 45-min time limit. No significant
      changes in peak muscle activation levels as well as no significant shifts in
      median frequency in the six muscle analysed were recorded during the 4.83-km
      hike. Significantly different peak muscle activation levels were recorded in four
      of the six muscles tested when the PHT was compared to the rakehoe task. These
      results suggest the PHT should not be administered in isolation and other tests
      that specifically challenge upper body muscle endurance should be incorporated
      into a battery that accurately assesses the job-specific fitness of wildfire
      fighters.

PMID- 22981471
TI  - Two new nonacosanetriols from Ginkgo biloba sarcotesta.
AB  - Two new fatty alcohols named as (7S,8R,11S)-nonacosanetriol (1) and (10R,12R,15S)
      nonacosanetriol (2), along with eight known compounds including ginkgolic acid
      (3), hydroginkgolic acid (4), sciadopitysin (5), ginkgetin (6), isoginkgetin (7),
      ginkgolide A (8), ginkgolide B (9) and ginkgolide C (10) have been isolated from
      the petroleum ether extract of Ginkgo biloba sarcotesta. Their structures were
      elucidated by means of chemical and extensive spectroscopic analysis. The
      absolute stereochemistry of compounds 1 and 2 was elucidated on the spectroscopic
      analysis of the R- and S-MTPA esters. Compounds 1 and 2 exhibited slight activity
      of antithrombin and moderate activity of antiplatelet aggregation in vitro. This
      was the first report regarding the anticoagulative activities of biflavonoids in
      G. biloba, and isoginkgetin (7) showed significant antithrombin and antiplatelet
      aggregation activity.

PMID- 22981472
TI  - [Long-term quality of life after pediatric liver transplantation].
AB  - We assessed quality of life in children after liver transplantation (LT) for at
      least 5years and in their parents, taking into account the physical,
      psychological, and social components, then compared the results of the patients
      with those of the general population and investigated the association between
      quality of life and somatic and psychosocial factors. Thirty-three patients, aged
      8 to 18years and with a mean follow-up of 11.4years were included. Quality of
      life was assessed using generic self-administered questionnaires in 3 versions
      depending on age (pre-teens, teens, parents): the AUQUEI, OK Ado, and SQLP,
      respectively. Patient quality of life improved with age for all components and
      adolescent patients could exceed that of the general population. There was a
      negative impact of LT on parental quality of life, but family cohesion was
      strengthened. The parameters associated with patient quality of life were
      primarily psychosocial parameters, with special consideration for siblings and
      school. The somatic parameters related to LT had little impact on the quality of
      life of the patients but were strongly correlated with parental scores,
      especially when there were complications related to LT or immunosuppression.
      Quality-of-life assessment is complementary to clinical and laboratory data and
      is essential to optimize patient monitoring. Parental assessment is essential
      because of the long-term impact of LT on these families. A regular assessment of
      the quality of life of young liver transplant recipients is necessary to
      determine whether the encouraging results are confirmed on a larger cohort.

PMID- 22981473
TI  - [Fulminant pneumonia during varicella in an immunocompetent 16-month-old girl].
AB  - Varicella is a cosmopolitan communicable disease caused by varicella-zoster virus
      (VZV) characterized by papulovesicular rash and fever. Management of fever and
      pruritus and prevention of bacterial infection are the main aspects of treatment.
      Severe complications and death may occur in pregnancy, in newborns, in adults,
      and in immunocompromised children. Contrary to immunocompetent adults in whom
      pneumonia occurs in 50% of cases during varicella, this complication in children
      is rare. We report a fatal case of pneumonia with severe hypoxemia during
      varicella in an immunocompetent 16-month-old child. Based on a literature review,
      we discuss the main aspects of diagnosis, treatment, and prognosis of varicella.
      Active immunization of children after 12 months of age is the primary prevention
      of varicella.

PMID- 22981474
TI  - [Clinical prediction tools: when epidemiologists help clinicians in the decision
      making process].

PMID- 22981475
TI  - [A rare cause of respiratory failure in infants: distal spinal-muscular atrophy 1
      (DSMA1 or SMARD1)].
AB  - Distal spinal-muscular atrophy 1 (DSMA1) or spinal-muscular atrophy with
      respiratory distress type 1 (SMARD1) is a rare neuromuscular disorder resulting
      from IGHMBP2 mutations. It is an autosomal recessive disease. We present the case
      of a 1-year-old girl admitted for respiratory failure associated with pneumonia.
      Right hemidiaphragmic elevation on the chest radiograph and distal retractions
      suggested the diagnosis of DSMA1. It was confirmed by muscle biopsy and molecular
      analysis. This unrecognized diagnosis should be considered when respiratory
      failure develops in the first year of life and is associated with diaphragmatic
      paralysis and distal muscle atrophy. Electromyography with measurement of nerve
      conduction velocity and muscle biopsy suggest the diagnosis, which must be
      confirmed by genetic analysis. After identifying the mutations, it is possible to
      perform prenatal diagnosis.

PMID- 22981476
TI  - [Peritonitis following gastroduodenal ulcer perforation disease in children:
      report of 4 cases].
AB  - Peritonitis due to gastroduodenal ulcer perforation disease is a rare entity in
      pediatric surgery. In Senegal, no study has been dedicated to ulcer complications
      in children. The aim of this study was to describe the epidemiology, diagnosis,
      and treatment of perforated peptic ulcer in patients less than 15 years old. This
      retrospective study was conducted in the Surgical Emergencies and Paediatric
      Surgery Department at Aristide Le Dantec University Hospital Center in Dakar,
      Senegal, during a period of 11 years (January 1999 to December 2010). We found 4
      children who presented perforated gastroduodenal ulcer: 3 females and 1 male. The
      average age of these patients was 9 years (range, 7-14 years). No family history
      was found. We noted 3 cases of perforated duodenal ulcer and one perforated
      gastric ulcer. The clinical diagnosis was suspected based on a peritoneal
      irritation syndrome. A plain x-ray of the abdomen was taken in all patients,
      which objectified a pneumoperitoneum image in 3 cases. The leukocytosis was
      constant. Treatment in all patients consisted on pre-, intra-, and postoperative
      intensive care, supra- and infraumbilical midline laparotomy, which allowed us to
      perform a debridement-suture of the gap followed by epiploplasty and extensive
      washing with lukewarm physiologic serum. Adjuvant therapy based on anti-ulcer and
      antibiotic therapy was initiated. Bacteriological examination of peritoneal fluid
      isolated a polymicrobial flora. Helicobacter pylori was not isolated.
      Histological examination of the biopsied perforation edges showed a benign ulcer
      in all cases. The follow-up endoscopy was performed 4 weeks after surgery and
      showed cicatrization of the ulcer in all patients. After a mean of 2 years, no
      recurrence was noted. The gastric or duodenal ulcer in children is rare. It is
      often discovered at the stage of perforation, a complication for which the
      essential treatment is surgery. Routine screening would certainly help to reduce
      the risk of this complication.

PMID- 22981477
TI  - [Epidemiology of equestrian injuries in children].
AB  - PURPOSE: Children increasingly participate in horseback riding, especially young
      girls, with more and more accidents during this activity. The severity of the
      injuries caused by horses seems to be higher than in other sports. METHODS: In a
      retrospective study, we reviewed 303 accidents of children younger than 15 years
      of age during the past 13 years. Our study only investigated children who were
      hospitalized after their accident. RESULTS: Eighty-two percent of the injured
      children were girls, but there was no difference between girls and boys in terms
      of severity. In most cases, children were hurt by falling from the horse (87 %).
      In the other cases, they were kicked or bitten by the animal. The most frequent
      trauma sustained was fracture (50 %). The upper extremity was injured in 40 % of
      the traumas followed by the head (32 %). The lower limbs, the abdomen, the spine,
      or the thorax were injured in less than 10 % of the incidents. The severity of
      the accidents was studied with the Injury Severity Score and we compared groups
      of children. Children younger than 11 years old were more severely injured than
      older children (P=0.0002). CONCLUSION: The youngest horseback riders should be
      supervised carefully to avoid severe injuries during this activity.

PMID- 22981479
TI  - [Acute leukemia in children in Brazzaville].

PMID- 22981480
TI  - T1-weighted MRI imaging features of pathologically proven non-pedal
      osteomyelitis.
AB  - RATIONALE AND OBJECTIVES: The objective of our study was to determine if the T1
      weighted magnetic resonance imaging (MRI) features associated with diabetic pedal
      osteomyelitis are present in histopathologically proven cases of non-pedal
      osteomyelitis. MATERIALS AND METHODS: Seventy-five patients with a
      histopathologically proven diagnosis of non-pedal osteomyelitis and a
      preoperative MRI were identified between 2000 and 2007. The MRIs were
      retrospectively reviewed for signal characterization of T1-weighted images,
      including the signal intensity compared with skeletal muscle, distribution of
      abnormal signal intensity, and pattern of abnormal signal intensity. A subsequent
      chart review was performed to identify potential clinical factors that were more
      associated with atypical T1 features of osteomyelitis. Fisher's exact test was
      performed to determine if there was a statistically significant difference in the
      T1-weighted imaging features of the hematogenous and nonhematogenous mechanisms
      of infection. RESULTS: Seventy of 75 cases demonstrated T1-weighted imaging
      features typical of pedal osteomyelitis with a confluent region of decreased
      signal intensity, hypointense, or isointense relative to skeletal muscle in a
      geographic pattern with medullary distribution. Of the 5 cases that did not
      demonstrate the typical T1 features associated with pedal osteomyelitis, 4 were
      considered to have a hematologic mechanism of infection given the absence of
      surgery, skin ulceration, or a penetrating injury. CONCLUSION: The majority of
      cases of non-pedal osteomyelitis in our study demonstrate the typical T1-weighted
      imaging features previously documented to correlate with the diagnosis of pedal
      osteomyelitis. The cases in our series that did not demonstrate the typical T1
      weighted features were predominantly secondary to a hematologic mechanism of
      infection.

PMID- 22981481
TI  - Vessel specific coronary artery calcium scoring: an automatic system.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to automatically detect and
      quantify calcium lesions for the whole heart as well as per coronary artery on
      non-contrast-enhanced cardiac computed tomographic images. MATERIALS AND METHODS:
      Imaging data from 366 patients were randomly selected from patients who underwent
      computed tomographic calcium scoring assessments between July 2004 and May 2009
      at Erasmum MC, Rotterdam. These data included data sets with 1.5-mm and 3.0-mm
      slice spacing reconstructions and were acquired using four different scanners.
      The scores of manual observers, who annotated the data using commercially
      available software, served as ground truth. An automatic method for detecting and
      quantifying calcifications for each of the four main coronary arteries and the
      whole heart was trained on 209 data sets and tested on 157 data sets. Statistical
      testing included determining Pearson's correlation coefficients and Bland-Altman
      analysis to compare performance between the system and ground truth. Wilcoxon's
      signed-rank test was used to compare the interobserver variability to the
      system's performance. RESULTS: Automatic detection of calcified objects was
      achieved with sensitivity of 81.2% per calcified object in the 1.5-mm data set
      and sensitivity of 86.6% per calcified object in the 3.0-mm data set. The system
      made an average of 2.5 errors per patient in the 1.5-mm data set and 2.2 errors
      in the 3.0-mm data set. Pearson's correlation coefficients of 0.97 (P < .001) for
      both 1.5-mm and 3.0-mm scans with respect to the calcium volume score of the
      whole heart were found. The average R values over Agatston, mass, and volume
      scores for each of the arteries (left circumflex coronary artery, right coronary
      artery, and left main and left anterior descending coronary arteries) were 0.93,
      0.96, and 0.99, respectively, for the 1.5-mm scans. Similarly, for 3.0-mm scans,
      R values were 0.94, 0.94, and 0.99, respectively. Risk category assignment was
      correct in 95% and 89% of the data sets in the 1.5-mm and 3-mm scans.
      CONCLUSIONS: An automatic vessel-specific coronary artery calcium scoring system
      was developed, and its feasibility for calcium scoring in individual vessels and
      risk category classification has been demonstrated.

PMID- 22981482
TI  - Comparison of FilmArray Respiratory Panel and laboratory-developed real-time
      reverse transcription-polymerase chain reaction assays for respiratory virus
      detection.
AB  - The FilmArray Respiratory Panel (Idaho Technology) is a highly multiplexed
      respiratory virus real-time polymerase chain reaction (PCR) assay. Eighty-four
      respiratory viruses identified by laboratory-developed real-time reverse
      transcription-PCR assays (LDA) or by viral cultures were mixed and tested by
      FilmArray to assess its performance. FilmArray identified 72 (90%) of 80 viruses
      also detected by LDA. Six of the 8 viruses not detected by FilmArray had PCR
      cycle threshold values >35. Compared to LDA, FilmArray showed comparable
      sensitivity when used to test serial dilutions of virus mixtures and good
      agreement with negative samples. With the use of 1 FilmArray instrument, 7
      clinical samples could be analyzed and reported in an 8-h shift compared to 20
      using LDA and 1 real-time detection instrument. While the FilmArray was rapid and
      easy to use, its low throughput and qualitative results may be a disadvantage in
      some clinical settings.

PMID- 22981483
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a
      Spanish hospital over a 4-year period: clonal replacement, decreased
      antimicrobial resistance, and identification of community-acquired and livestock
      associated clones.
AB  - This study was carried out on 189 methicillin-resistant Staphylococcus aureus
      (MRSA) clinical isolates collected in a third-level hospital in Valladolid,
      Spain, between 2005 and 2008 in order to investigate the changes in molecular
      epidemiology and genetic backgrounds associated with the changes in resistance
      phenotypes produced over time. The MRSA isolates were classified as belonging to
      10 different clones, including the identification of a novel MRSA clone, ST2422
      MRSA-IV, belonging to CC121; 1 CA-MRSA strain from a USA300 clone; another from
      ST97-MRSA-IV, associated with clones adapted to livestock (LA-MRSA); and 2
      strains belonging to a new spa type (t10258) related to the ST8-MRSA-IV clone.
      Sixty-two percent of the strains belonging to Spanish-prevalent MRSA sequence
      type ST125 harboured composite or multiple SCCmec elements including SCCmec type
      IV plus ccrA/B4 (ST125-SCCmec IV/VI). In the years studied, it was observed that
      ST125-SCCmec IV/VI replaced the multiresistant ST228-SCCmec I previously
      prevalent, and, as a consequence, decreased gentamicin and clindamycin resistance
      was further observed.

PMID- 22981484
TI  - Guided wave propagation in uncertain elastic media.
AB  - In this paper, the authors present a numerical approach to study the guided
      elastic wave propagation in uncertain elastic media. Stochastic wave finite
      element method (S.W.F.E.M) formulation with consideration of spatial variability
      of material and geometrical properties is developed for probabilistic analysis of
      structures. The uncertain material properties are modelled as a set of random
      fields. The idea is to consider the random fields as a supplementary dimension of
      the problem through the spatial discretisation using the finite elements process.
      The stochastic forced response is formulated to study the stochastic dynamical
      behavior of the structure using the appropriate boundary conditions. In this
      work, a SWFE approach is employed in order to analyse the stochastic wave
      propagation and the numerical accuracy. The computational efficiency of the
      method is demonstrated by comparison with Monte Carlo simulations.

PMID- 22981485
TI  - Effects of foot posture on fifth metatarsal fracture healing: a finite element
      study.
AB  - The goal of this study was to evaluate the effects of maintaining different foot
      postures during healing of proximal fifth metatarsal fractures for each of 3
      common fracture types. A 3-dimensional (3D) finite element model of a human foot
      was developed and 3 loading situations were evaluated, including the following:
      (1) normal weightbearing, (2) standing with the affected foot in dorsiflexion at
      the ankle, and (3) standing with the affected foot in eversion. Three different
      stages of the fracture-healing process were studied, including: stage 1, wherein
      the material interposed between the fractured edges was the initial connective
      tissue; stage 2, wherein connective tissue had been replaced by soft callus; and
      stage 3, wherein soft callus was replaced by mature bone. Thus, 30 3D finite
      element models were analyzed that took into account fracture type, foot posture,
      and healing stage. Different foot postures did not statistically significantly
      affect the peak-developed strains on the fracture site. When the fractured foot
      was everted or dorsiflexed, it developed a slightly higher strain within the
      fracture than when it was in the normal weightbearing position. In Jones
      fractures, eversion of the foot caused further torsional strain and we believe
      that this position should be avoided during foot immobilization during the
      treatment of fifth metatarsal base fractures. Tuberosity avulsion fractures and
      Jones fractures seem to be biomechanically stable fractures, as compared with
      shaft fractures. Our understanding of the literature and experience indicate that
      current clinical observations and standard therapeutic options are in accordance
      with the results that we observed in this investigation, with the exception of
      Jones fractures.

PMID- 22981486
TI  - Changing perceptions of transtibial amputation.

PMID- 22981487
TI  - Prediction of acute mountain sickness by pulse oximetry: what are the right
      questions?

PMID- 22981488
TI  - Application of empirical predictive modeling using conventional and alternative
      fecal indicator bacteria in eastern North Carolina waters.
AB  - Coastal and estuarine waters are the site of intense anthropogenic influence with
      concomitant use for recreation and seafood harvesting. Therefore, coastal and
      estuarine water quality has a direct impact on human health. In eastern North
      Carolina (NC) there are over 240 recreational and 1025 shellfish harvesting water
      quality monitoring sites that are regularly assessed. Because of the large number
      of sites, sampling frequency is often only on a weekly basis. This frequency,
      along with an 18-24 h incubation time for fecal indicator bacteria (FIB)
      enumeration via culture-based methods, reduces the efficiency of the public
      notification process. In states like NC where beach monitoring resources are
      limited but historical data are plentiful, predictive models may offer an
      improvement for monitoring and notification by providing real-time FIB estimates.
      In this study, water samples were collected during 12 dry (n = 88) and 13 wet (n
      = 66) weather events at up to 10 sites. Statistical predictive models for
      Escherichiacoli (EC), enterococci (ENT), and members of the Bacteroidales group
      were created and subsequently validated. Our results showed that models for EC
      and ENT (adjusted R(2) were 0.61 and 0.64, respectively) incorporated a range of
      antecedent rainfall, climate, and environmental variables. The most important
      variables for EC and ENT models were 5-day antecedent rainfall, dissolved oxygen,
      and salinity. These models successfully predicted FIB levels over a wide range of
      conditions with a 3% (EC model) and 9% (ENT model) overall error rate for
      recreational threshold values and a 0% (EC model) overall error rate for
      shellfish threshold values. Though modeling of members of the Bacteroidales group
      had less predictive ability (adjusted R(2) were 0.56 and 0.53 for fecal
      Bacteroides spp. and human Bacteroides spp., respectively), the modeling approach
      and testing provided information on Bacteroidales ecology. This is the first
      example of a set of successful statistical predictive models appropriate for
      assessment of both recreational and shellfish harvesting water quality in
      estuarine waters.

PMID- 22981489
TI  - Solar disinfection of wastewater to reduce contamination of lettuce crops by
      Escherichia coli in reclaimed water irrigation.
AB  - Low-cost disinfection methods to allow safe use of recycled wastewater for
      irrigation can have important beneficial implications in the developing world.
      This study aims to assess the efficiency of solar disinfection to reduce
      microbial contamination of lettuce crops when solar-treated wastewater effluents
      are used for irrigation. The irrigation study was designed as a complete
      experimental loop, including (i) the production of irrigation water through solar
      disinfection of real municipal wastewater treatment plant effluents (WWTPE), (ii)
      the watering of cultivated lettuce crops at the end of solar treatment, and (iii)
      the detection of microbial contamination on the irrigated crops 24 h after
      irrigation. Solar disinfection was performed using two types of reactors: (i) 20
      L batch borosilicate glass reactors equipped with CPC to optimize solar
      irradiation, and (ii) 1.5-L PET bottles, i.e. the traditional SODIS recipients
      commonly used for disinfection of drinking water in developing communities. Both
      solar and H(2)O(2)-aided solar disinfection processes were tested during <=5 h
      exposure of WWTPE, and Escherichia coli inactivation was analysed. A
      presence/absence detection method was developed to analyse lettuce leaves sampled
      24 h after watering for the detection of E. coli. Results of inactivation assays
      show that solar disinfection processes can bring down bacterial concentrations of
      >10(3)-10(4)E. coli CFU mL(-1) in real WWTPE to <2 CFU/mL (detection limit). The
      absence of E. coli on most lettuce samples after irrigation with solar
      disinfected effluents (26 negative samples/28) confirmed an improved safety of
      irrigation practices due to solar treatment, while crops irrigated with raw WWTPE
      showed contamination.

PMID- 22981490
TI  - A framework for identifying characteristic odor compounds in municipal wastewater
      effluent.
AB  - Municipal wastewater often contains trace amounts of organic compounds that can
      compromise aesthetics of drinking water and undermine public confidence if a
      small amount of effluent enters the raw water source of a potable water supply.
      To efficiently identify compounds responsible for odors in wastewater effluent,
      an analytical framework consisting of gas chromatography with mass spectrometry
      (GC-MS) and gas chromatography with olfactometry detection (GC-Olf) coupled with
      flavor profile analysis (FPA) was used to identify and monitor compounds that
      could affect the aesthetics of drinking water. After prioritizing odor peaks
      detected in wastewater effluent by GC-Olf, the odorous components were
      tentatively identified using retention indices, mass spectra and odor
      descriptors. Wastewater effluent samples were typically dominated by earthy-musty
      odors with additional odors in the amine, sulfidic and fragrant categories. 2,4,6
      trichloroanisole (246TCA), geosmin and 2-methylisoborneol (2MIB) were the main
      sources of the earthy/musty odors in wastewater effluent. The other odors were
      attributable to a suite of compounds, which were detected in some but not all of
      the wastewater effluents at levels well in excess of their odor thresholds. In
      most cases, the identities of odorants were confirmed using authentic standards.
      The fate of these odorous compounds, including 2-pyrrolidone, methylnaphthalenes,
      vanillin and 5-hydroxyvanillin (5-OH-vanillin), should be considered in future
      studies of water systems that receive effluent from upstream sources.

PMID- 22981491
TI  - Chlorine disinfection by-products in wastewater effluent: Bioassay-based
      assessment of toxicological impact.
AB  - The potential ecological impact of disinfection by-products (DBPs) present in
      chlorinated wastewater effluents is not well understood. In this study, the
      chlorinated effluent of traditional wastewater treatment plants (WWTPs) and
      advanced water reclamation plants (AWRPs) supplying highly-treated recycled water
      were analyzed for nitrosamines and trihalomethanes (THMs), and a battery of
      bioassays conducted to assess effluent toxicity. An increase in general toxicity
      from DBPs was revealed for all wastewaters studied using an in vitro
      bioluminescence assay. Examples of androgenic activity and estrogenic activity
      arising from DBPs at specific sampling sites were also observed. The in vivo
      model (Artemia franciscana) was generally not adversely affected by exposure to
      DBPs from any of the chlorinated wastewaters studied. The observed toxicity could
      not be related to the concentrations of THMs and nitrosamines present, indicating
      that DBPs not monitored in this study were responsible for this. This work
      highlights the complexity of DBPs mixtures formed in chlorinated wastewaters,
      illustrating that toxicity of wastewater DBPs cannot be predicted by chemical
      monitoring of THMs and nitrosamines. The results suggest bioassays may be
      particularly useful monitoring tools in assessing toxicity arising from DBPs of
      these complex waters. The research concludes that DBPs formed in the chlorinated
      wastewaters studied can be toxic and may have a deleterious impact on aquatic
      organisms that are exposed to them, and therefore, that chlorination or
      chlorination/dechlorination may not be adequate treatment strategies for the
      protection of receiving waters. Chlorinated wastewater toxicity (from DBPs) is
      not well-understood in the Australian context, and this study serves to advise
      regulators on this issue.

PMID- 22981492
TI  - Differentiating sources of anthropogenic loading to impaired water bodies
      utilizing ratios of sucralose and other microconstituents.
AB  - Previous studies have suggested the use of sucralose, a synthetic non-nutritive
      sweetener, as an indicator of domestic wastewater loading to surface waters. This
      paper presents a novel flow schematic approach for quantifying volumetric load
      contributions from different water sources by utilizing sucralose as a master
      diagnostic variable in combination with other trace compounds. This conceptual
      approach was validated through demonstration of sucralose presence at positive
      field sites susceptible to either water reuse or septic infiltration and its
      absence at negative field sites. Differences in the ratios of carbamazepine to
      sucralose and gadolinium anomaly to sucralose were demonstrated for eight septic
      and water reuse effluents. Utilization of these ratios as a means of
      distinguishing septic and water reuse loading to water bodies merits additional
      study. In the absence of sustained loading, the use of carbamazepine might be
      hindered by photolysis and gadolinium anomaly might be hindered when volumetric
      loading is less than 20%.

PMID- 22981493
TI  - Influence of novel naphthalimide-based organoselenium on genotoxicity induced by
      an alkylating agent: the role of reactive oxygen species and selenoenzymes.
AB  - OBJECTIVE: The protection conferred by a series of synthetic organoselenium
      compounds against genotoxicity and oxidative stress induced by a reference
      mutagen cyclophosphamide (CP) was assessed. METHOD: Genotoxicity was induced in
      mice by CP treatment (25 mg/kg b.w.) for 10 consecutive days. Organoselenium
      compounds (3 mg/kg b.w.) were administered orally in a concomitant and
      pretreatment schedule. DNA damage in peripheral blood lymphocytes and frequency
      of chromosomal aberration in the bone marrow cells were measured. Liver tissues
      were collected for analysis of the activity of antioxidant and detoxifying
      enzymes, lipid peroxidation (LPO) level, glutathione content, and histopathology.
      RESULTS: Exposure to CP not only led to a significant increase in the percent of
      chromosomal aberration and DNA damage, but also enhanced generation of hepatic
      reactive oxygen species (ROS) and LPO level. The organoselenium compounds
      demonstrated marked functional protection against CP-induced genotoxicity. DNA
      damage and chromosomal aberration along with ROS generation were attenuated in
      the organoselenium-treated mice compared with the CP-treated control mice. CP
      caused marked depression in the activities of the selenoenzymes (glutathione
      peroxidase (GPx) and thioredoxin reductase (TRxR)) and other detoxifying and
      antioxidant enzymes, while treatment with organoselenium compounds restored all
      these activities towards normal. DISCUSSION: The protective effect of these
      compounds may be primarily associated with the improvement of the activity of
      antioxidant and detoxifying enzymes (including the selenoenzymes, GPx, and TRxR)
      that are known to protect the DNA and other cellular components from oxidative
      damage.

PMID- 22981496
TI  - A supermicrosurgical magnification enhancer for lymphaticovenular anastomosis.

PMID- 22981497
TI  - Increments in ischaemia time induces microvascular complications in the DIEP flap
      for breast reconstruction.
AB  - BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is
      currently one of the preferred methods of autologous breast reconstruction. As a
      microsurgical flap, it is subjected to ischaemia-reperfusion injury and no reflow
      phenomenon, both of which are influenced by prolonged ischaemia times. In this
      work, we review the rates of microvascular complications according to ischaemia
      times in patients submitted to DIEP flap breast reconstruction. METHODS: A
      retrospective review of 182 patients submitted to breast reconstruction with DIEP
      flap was conducted. Patients were first classified according to ischaemia time
      percentiles 25, 50, 75 and 100 comparing the rates of microvascular complications
      using Fisher's exact test. Next, patients were separated in two groups above and
      below P(50). Using Student's t-test and Fisher's exact test, univariate analysis
      was conducted to compare all demographic and surgical variables as well as
      complications between these groups. Finally, multivariate analysis using binary
      logistic regression was performed to determine whether or not ischaemia time was
      an independent risk factor for microvascular complications. RESULTS: Flap success
      rate was 97%. Eighteen flaps (9.5%) presented some form of microvascular event.
      Higher rates of complications were observed as ischaemia time increased (p <
      0.05). On multivariate analysis, ischaemia time was found to be an independent
      risk factor for microvascular complications (odds ratio (OR) 3.81, p = 0.03).
      Flaps with ischaemia longer than 1.5-2 h were observed to be at higher risk of
      developing some form of vascular compromise. CONCLUSIONS: Ischaemia time is an
      independent risk factor for microvascular complications in the DIEP flap for
      breast reconstruction. Keeping such time to the minimum necessary and avoiding
      needless delays is likely to improve flap survival.

PMID- 22981498
TI  - Panobinostat activity in both bexarotene-exposed and -naive patients with
      refractory cutaneous T-cell lymphoma: results of a phase II trial.
AB  - BACKGROUND: Panobinostat is a potent, oral pan-deacetylase inhibitor (pan-DACi)
      that increases the acetylation of proteins involved in multiple oncogenic
      pathways. Here, panobinostat is studied in bexarotene-exposed and -naive patients
      with refractory cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: Patients
      with CTCL subtypes mycosis fungoides and Sezary syndrome who received ?2 prior
      systemic therapy regimens received panobinostat (20mg) three times every week.
      The primary objective was overall response rate (ORR) as determined by a combined
      evaluation of skin disease and involvement of lymph node and viscera. Disease
      progression was defined as an unconfirmed, ?25% increase in modified Severity
      Weighted Assessment Tool (mSWAT) compared with nadir. RESULTS: Seventy-nine
      bexarotene-exposed and 60 bexarotene-naive patients were enrolled. Reductions in
      baseline mSWAT scores were observed in 103 patients (74.1%). The ORR was 17.3% in
      all patients in the primary analysis (15.2% and 20.0% in the bexarotene-exposed
      and -naive groups, respectively). The median progression-free survival was 4.2
      and 3.7 months in the bexarotene-exposed and -naive groups, respectively. The
      median duration of response was 5.6 months in the bexarotene-exposed patients and
      was not reached at data cutoff in the bexarotene-naive patients. Additional
      responses were observed when less-stringent progression criteria were used. The
      most common adverse events were thrombocytopenia, diarrhoea, fatigue and nausea.
      Thrombocytopenia and neutropenia were the only grade 3/4 adverse events in >5% of
      patients and were manageable. CONCLUSION: Despite a very conservative definition
      of disease progression, panobinostat demonstrated activity with a manageable
      safety profile in bexarotene-exposed and -naive CTCL patients. ClinicalTrials.gov
      Identifier: NCT00425555.

PMID- 22981499
TI  - Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by
      radiotherapy with cetuximab for locally advanced squamous cell carcinoma of the
      head and neck.
AB  - PURPOSE: To determine the efficacy and feasibility of induction chemotherapy
      (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and
      cetuximab (C) in patients with locally advanced head and neck cancer. PATIENTS
      AND METHODS: Forty-nine previously untreated patients with local advanced stage
      III and IV squamous cell carcinoma of the head and neck (SCCHN) received three
      courses of ICT consisting of docetaxel 75mg/m(2) day 1, cisplatin 75mg/m(2) day 1
      and infusional 5-fluorouracil 750mg/m(2)/day on days 1-5 followed by radiotherapy
      plus C at 250mg/m(2)/week (after an initial loading dose of 400mg/m(2)). RESULTS:
      After completion of ICT 44 of 49 patients received radiotherapy plus C. Three
      months after therapy completion tumour response was observed in 33 patients and
      after two years, 25 patients were in complete remission (CR). The most common
      grade 4 toxicity during the whole treatment period was dermatitis (30%), followed
      by mucositis (27%) and neutropenia (17%) without fever. One toxic related death
      was observed during ICT. Two-year progression-free survival (PFS) rate was 59%
      and two-year overall survival (OS) rate was 63%, respectively. CONCLUSION:
      Concurrent radiotherapy plus C after three courses of ICT was feasible and was
      associated with promising CR, PFS and OS rates. Further optimisation of dose and
      sequence is warranted.

PMID- 22981500
TI  - (18)F-labelled fluorodeoxyglucose-positron emission tomography (FDG-PET)
      heterogeneity of response is prognostic in dabrafenib treated BRAF mutant
      metastatic melanoma.
AB  - BACKGROUND: Little is known about the prevalence and clinical significance of
      heterogeneity of positron emission tomography with (18)F-labelled
      fluorodeoxyglucose-positron emission tomography (FDG-PET) response. We aim to
      determine the prevalence, and clinicopathologic correlates of intra-patient
      heterogeneity of FDG-PET response in metastatic melanoma treated with dabrafenib,
      and to determine whether heterogeneity predicts clinical outcome. METHODS:
      Patients with BRAF mutant metastatic melanoma and >= 2 FDG avid lesions treated
      on the Phase I trial of dabrafenib at a single institution (n=23) were included.
      FDG-PET response was assessed by comparing baseline PET scans with scans at day
      15. A heterogeneous response was defined as responding and new or metabolically
      progressing lesion(s) in a patient, or >10% of lesions with a stable metabolic
      response and responding lesions in a patient. RESULTS: Six (26%) patients had a
      heterogeneous PET response. The median time to progression (TTP) was 7.4 months
      (95% confidence interval (CI): 6.5-8.3) for PET homogeneous responders and 3.0
      months (95%CI: 0.6-5.4) for PET heterogeneous responders. There were no
      homogeneous non-responders. Age, BRAF mutation genotype, dose, and lactate
      dehydrogenase, did not predict for heterogeneity of PET response. Heterogeneity
      did not correlate with tumour response. Lung metastases were more likely to
      respond than other visceral metastatic sites. CONCLUSIONS: Heterogeneous FDG-PET
      responses are common in metastatic melanoma treated with dabrafenib, and
      heterogeneity is associated with a shorter TTP. FDG-PET heterogeneity may predict
      molecular heterogeneity, and FDG-PET directed biopsies may facilitate
      investigation into mechanisms of resistance to signal pathway inhibitors.

PMID- 22981501
TI  - Diagnosis and treatment of melanoma. European consensus-based interdisciplinary
      guideline--Update 2012.
AB  - Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and
      causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary
      experts from the European Dermatology Forum (EDF), the European Association of
      Dermato-Oncology (EADO) and the European Organization of Research and Treatment
      of Cancer (EORTC) was formed to make recommendations on CM diagnosis and
      treatment, based on systematic literature reviews and the experts' experience.
      Diagnosis is made clinically and staging is based upon the AJCC system. CMs are
      excised with one to two centimetre safety margins. Sentinel lymph node dissection
      (SLND) is routinely offered as a staging procedure in patients with tumours more
      than 1mm in thickness, although there is as yet no clear survival benefit for
      this approach. Interferon-alpha treatment may be offered to patients with stage
      II and III melanoma as an adjuvant therapy, as this treatment increases at least
      the disease-free survival (DFS) and less clear the overall survival (OS) time.
      The treatment is however associated with significant toxicity. In distant
      metastasis, all options of surgical therapy have to be considered thoroughly. In
      the absence of surgical options, systemic treatment is indicated. BRAF inhibitors
      like vemurafenib for BRAF mutated patients as well as the CTLA-4 antibody
      ipilimumab offer new therapeutic opportunities apart from conventional
      chemotherapy. Therapeutic decisions in stage IV patients should be primarily made
      by an interdisciplinary oncology team ('tumour board').

PMID- 22981502
TI  - The effect of Astragaloside IV on immune function of regulatory T cell mediated
      by high mobility group box 1 protein in vitro.
AB  - High mobility group box 1 protein (HMGB1), a potent pro-inflammatory cytokine,
      contributes to the pathogenesis of diverse inflammatory and infectious disorders.
      Some studies have illustrated the potential effect of HMGB1 on regulatory T cells
      (Tregs). Astragaloside IV (AST IV) isolated from a Chinese herb, Astragalus
      mongholicus, is known to have a variety of immunomodulatory activities. However,
      it is not yet clear whether AST IV possesses potential regulatory effect on the
      pro-inflammatory ability of HMGB1 with subsequent activation of Tregs. This study
      was carried out to investigate the antagonistic effects of different doses of AST
      IV on the immune function of Tregs mediated by HMGB1 in vitro. Tregs isolated
      from the spleens of mice were co-cultured with HMGB1 and/or AST IV. Cell
      phenotypes of Tregs were analyzed, and the contents of various cytokines in the
      cell supernatants as a result of co-culture and the proliferation of CD4(+)CD25(
      ) T cells were determined. Results showed that HMGB1 stimulation resulted in
      significantly down-regulation of expressions of Tregs cell phenotypes. However,
      AST IV can rival the suppressing effect of HMGB1 on immune function of Tregs with
      a dose-dependent in vitro. These results indicate that AST IV has the potential
      therapeutic action on inflammation augmented by HMGB1.

PMID- 22981503
TI  - Extract of Magnoliae Flos inhibits ovariectomy-induced osteoporosis by blocking
      osteoclastogenesis and reducing osteoclast-mediated bone resorption.
AB  - Bone homeostasis is maintained by a balance between bone resorption by
      osteoclasts and bone formation by osteoblasts. Osteoporosis occurs when
      osteoclast activity surpasses osteoblast activity. Pro-inflammatory cytokines
      stimulate osteoclast differentiation and activity by increasing production of
      macrophage-colony stimulating factor and receptor activator of nuclear factor
      kappaB ligand (RANKL). In this study, we investigated whether Magnoliae Flos
      (MF), one of the most commonly used Chinese medicinal herbs for managing
      rhinitis, sinusitis and headache, could effectively inhibit osteoporosis. In
      ovariectomized (OVX) mice compared to sham mice, the body weight increased and
      serum levels of alkaline phosphatase (ALP), tartrate resistant acid phosphatase
      5b, calcium, and osteocalcin were significantly elevated. However, orally
      administrated MF extract substantially inhibited the increased body weight and
      serum levels of bone turnover markers, without any evidence of tissue toxicity.
      MF extract treatment significantly reversed the morphometric parameters of
      ovariectomy-induced bone loss, including trabecular bone volume, thickness,
      number, separation, and bone density, to almost the same levels of the sham mice.
      Furthermore, MF extract reduced the RANKL-mediated osteoclast differentiation and
      bone resorption by inhibiting the activities of matrix metalloproteinases (MMPs)
      and cathepsin K in mouse bone marrow macrophages. MF extract appeared to increase
      ALP activity in murine osteoblastic cells. Taken together, MF extract may be a
      beneficial supplement for the blockade of osteoporosis progression, particularly
      for the management of postmenopausal osteoporosis.

PMID- 22981504
TI  - Prenylated phloroglucinol derivatives from Hypericum sampsonii.
AB  - Six new acylphloroglucinol derivatives, sampsonols A-F (1-6), were isolated from
      the petroleum ether extract of the aerial parts of Hypericum sampsonii. The
      structures and relative configurations of sampsonols A-F were elucidated by
      extensive spectroscopic analyses. All these compounds were tested for their in
      vitro cytotoxic and anti-inflammatory activities. Sampsonols A and B (1 and 2)
      showed significant cytotoxicity against four human tumor cell lines with IC(50)
      values in the range of 13-28MUM, whereas sampsonols C and F (3 and 6) showed
      potent inhibitory activities against LPS-induced NO production in RAW 264.7
      macrophages with IC(50) values of 27.3 and 29.3MUM, respectively.

PMID- 22981505
TI  - Cytotoxic alkoxylated xanthones from the resin of Garcinia hanburyi.
AB  - Three new xanthones, garcinolic acid (1), 10alpha-ethoxy-9,10-dihydromorellic
      acid (2), and 10alpha-ethoxy-9,10-dihydrogambogenic acid (3), along with six
      known compounds were isolated from the resin of Garcinia hanburyi. These
      compounds were tested for their cytotoxicities against A549, HCT116, SK-BR-3 and
      HepG2, and showed high inhibitory effects on the cell lines.

PMID- 22981506
TI  - Optimization of a reversed-phase-high-performance thin-layer chromatography
      method for the separation of isoniazid, ethambutol, rifampicin and pyrazinamide
      in fixed-dose combination antituberculosis tablets.
AB  - This paper presents the development of a new RP-HPTLC method for the separation
      of pyrazinamide, isoniazid, rifampicin and ethambutol in a four fixed-dose
      combination (4 FDC) tablet formulation. It is a single method with two steps in
      which after plate development pyrazinamide, isoniazid and rifampicin are detected
      at an UV wavelength of 280 nm. Then ethambutol is derivatized and detected at a
      VIS wavelength of 450 nm. Methanol, ethanol and propan-1-ol were evaluated
      modifiers to form alcohol-water mobile phases. Systematic optimization of the
      composition of each alcohol in the mobile phase was carried out using the window
      diagramming concept to obtain the best separation. Examination of the Rf
      distribution of the separated compounds showed that separation of the compounds
      with the mobile phase containing ethanol at the optimal fraction was almost
      situated within the optimal Rf-values region of 0.20-0.80. Therefore, ethanol was
      selected as organic modifier and the optimal mobile phase composition was found
      to be ethanol, water, glacial acetic acid (>99% acetic acid) and 37% ammonia
      solution (70/30/5/1, v/v/v/v). The method is new, quick and cheap compared to the
      actual method in the International Pharmacopoeia for the assay of the 4 FDC
      tablets, which involves the use of two separate HPLC methods.

PMID- 22981507
TI  - Planar solid phase extraction clean-up for pesticide residue analysis in tea by
      liquid chromatography-mass spectrometry.
AB  - Efficient clean-up is indispensable for preventing matrix effects in multi
      residue analysis of pesticides in food by liquid and gas chromatography (LC and
      GC) coupled to mass spectrometry (MS). High-throughput planar solid phase
      extraction (HTpSPE) was recently introduced as a new clean-up concept in residue
      analysis of pesticides in fruit and vegetables (C. Oellig, W. Schwack, 2011
      [45]). Thin-layer chromatography (TLC) was used to completely separate pesticides
      from matrix compounds and to focus them into a sharp zone, followed by extraction
      of the target zone by the TLC-MS interface. As rather challenging matrices, tea
      samples were chosen in this study. Besides chlorophylls and polyphenols, high
      amount of caffeine is co-extracted resulting in strong matrix effects both in LC
      MS and GC-MS. The former HTpSPE procedure was adapted to initial extracts of
      green and black tea resulting in colorless extracts nearly free of matrix effects
      and interferences, as shown for seven chemically representative pesticides
      (acetamiprid, penconazole, azoxystrobin, chlorpyrifos, pirimicarb, fenarimol, and
      mepanipyrim). LC-MS/MS calibration curves obtained in the range of 0.002-0.5
      mg/kg from matrix-matched standards and solvent standards were nearly identical
      and demonstrated the effectiveness of clean-up by HTpSPE. Mean recoveries
      determined by LC-MS/MS against solvent standards at spiking levels of 0.01 and
      0.1 mg/kg ranged between 72 and 114% with relative standard deviations (RSDs) of
      0.7-4.7% (n=4), while LC-MS measurements of tea samples spiked at 1 mg/kg
      provided recoveries of 81-104% with RSDs of 1.2-4.9% (n=6). Using LC-MS/MS, the
      method showed high sensitivity with signal-to-noise ratios>10 for concentrations
      below 0.002 mg/kg. HTpSPE of one sample was done in a few minutes, while numerous
      samples were cleaned in parallel at minimal costs with very low sample and
      solvent consumption.

PMID- 22981509
TI  - Skin regeneration scaffolds: a multimodal bottom-up approach.
AB  - Skin wounds are a major social and financial burden. However, current treatments
      are suboptimal. The gradual comprehension of the finely orchestrated nature of
      intercellular communication has stimulated scientists to investigate growth
      factor (GF) or stem cell (SC) incorporation into suitable scaffolds for local
      delivery into wound beds in an attempt to accelerate healing. This review
      provides a critical evaluation of the status quo of current research into GF and
      SC therapy and subsequent future prospects, including benefits and possible long
      term dangers associated with their use. Additionally, we stress the importance of
      a bottom-up approach in scaffold fabrication to enable controlled factor
      incorporation as well as production of complex scaffold micro- and nanostructures
      resembling that of natural extracellular matrix.

PMID- 22981508
TI  - Oxidized high-density lipoprotein is associated with increased plasma glucose in
      non-diabetic dyslipidemic subjects.
AB  - BACKGROUND: Oxidized high-density lipoprotein (oxHDL) has reduced capacity for
      cholesterol efflux and some of other anti-atherogenic properties of HDL, but the
      role of oxHDL in the pathogenesis of cardiometabolic disease has not been fully
      demonstrated. This study investigated the association of oxHDL with plasma
      glucose (PG) and the other atherosclerotic risk variables in non-diabetic
      dyslipidemic subjects. METHODS: Conventional atherosclerotic markers and LDL
      particle size (LDL-PS), as determined by gel electrophoresis, were measured in
      155 non-diabetic subjects (mean age of 57 years) with dyslipidemia. Serum oxHDL
      levels were quantified using an antibody against oxidized human apoA-I in a
      sandwich ELISA format. RESULTS: Multiple regression analysis adjusted for
      possible confounders revealed that HDL-cholesterol was independently,
      significantly and positively correlated with LDL-PS and oxHDL. By multiple
      regression analysis, oxHDL was independently, significantly and positively
      correlated with fasting PG (beta=0.19, P=0.01). Subjects in the highest PG
      tertile group had approximately 30% higher oxHDL levels than the lowest PG
      tertile group. CONCLUSIONS: These results suggest that high PG levels may
      contribute to the HDL oxidation, irrespective of HDL-cholesterol levels, even in
      non-diabetic subjects with dyslipidemia, and that the measurement of oxHDL may be
      a useful marker of dysfunctional HDL.

PMID- 22981510
TI  - Prostanoids and inflammatory pain.
AB  - Prostanoids play pivotal roles in inflammation and pain. Cyclooxygenase (COX)
      inhibitors, the nonsteroidal anti-inflammatory drugs (NSAIDs), depress prostanoid
      formation and are widely used to treat inflammatory pain. However, their
      therapeutic benefit is offset by serious side-effects, primarily gastrointestinal
      and cardiovascular complications. Pathway elements downstream of the COX enzymes,
      particularly the terminal synthases and receptors of prostaglandin E2, have been
      proposed as alternative targets for the development of novel NSAID like drugs.
      Here, we summarize the current knowledge on the roles of individual prostanoids
      in modulating inflammatory pain. 

PMID- 22981512
TI  - Fluoroalkyl end-capped vinyltrimethoxysilane oligomer/anatase titanium oxide
      nanocomposites possessing photocatalytic activity even after calcination at 1000
      degrees C.
AB  - Fluoroalkyl end-capped vinyltrimethoxysilane oligomer [R(F)-(VM)(n)-R(F)]
      underwent the sol-gel reaction under alkaline conditions in the presence of
      anatase titanium oxide nanoparticles (an-TiO(2)) in tetrahydrofuran to give the
      corresponding fluorinated oligomer/anatase titanium oxide nanocomposites [R(F)
      (VM-SiO(2))(n)-R(F)/an-TiO(2)]. Crystalline structure of an-TiO(2) in the
      nanocomposites thus obtained was found to keep completely its structure without
      phase transformation to rutile even after calcination at 1000 degrees C, although
      crystalline structure of the original an-TiO(2) nanoparticles underwent a
      complete phase transformation to the rutile under similar conditions.
      Interestingly, R(F)-(VM-SiO(2))(n)-R(F)/an-TiO(2) nanocomposites before and after
      calcination at 1000 degrees C exhibited the similar photocatalytic activity for
      the decolorization of methylene blue under UV light irradiation.

PMID- 22981513
TI  - Self organization of inorganic nanocrystals: unexpected chemical and physical
      properties.
AB  - Here we point out that the nanocrystals well ordered in compact hexagonal
      networks are highly stable compared to the same nanocrystals either isolated on a
      substrate or ordered in a less compact manner. The emergence of unexpected
      collective physical intrinsic properties results in the nanocrystals being
      ordered over a long distance in colloidal crystals called supracrystals. Some
      morphologies of nanocrystals ordered, at the micrometer scale, in 3D
      superlattices called supracrystals are similar to those obtained with atoms in
      nanocrystals. From a comparison between vibrational and magnetic properties of
      supracrystals and aggregates composed of the same nanocrystals, it is proposed
      that nanocrystals in a supracrystal could behave as atoms in a nanocrystal. From
      these data a possible analogy between nanocrystals in a supracrystal and atoms in
      nanocrystals is proposed.

PMID- 22981511
TI  - An emerging link in stem cell mobilization between activation of the complement
      cascade and the chemotactic gradient of sphingosine-1-phosphate.
AB  - Under steady-state conditions, hematopoietic stem/progenitor cells (HSPCs) egress
      from bone marrow (BM) and enter peripheral blood (PB) where they circulate at low
      levels. Their number in PB, however, increases significantly in several stress
      situations related to infection, organ/tissue damage, or strenuous exercise.
      Pharmacologically mediated enforced egress of HSPCs from the BM microenvironment
      into PB is called "mobilization", and this phenomenon has been exploited in
      hematological transplantology as a means to obtain HSPCs for hematopoietic
      reconstitution. In this review we will present the accumulated evidence that
      innate immunity, including the complement cascade and the granulocyte/monocyte
      lineage, and the PB plasma level of the bioactive lipid sphingosine-1-phosphate
      (S1P) together orchestrate this evolutionarily conserved mechanism that directs
      trafficking of HSPCs. 

PMID- 22981514
TI  - Spectroscopic and theoretical studies on the nucleophilic substitution of 2,3
      dichloronaphthoquinone with para-substituted anilines in solid state via initial
      charge transfer complexation.
AB  - Various spectroscopy techniques (UV-Vis, DRS, FT-IR, (1)H NMR, LC-MS) and
      theoretical computations have been employed to investigate the mechanism of the
      nucleophilic substitution reaction of 2,3-dichloronaphthoquinone (DCNQ) with para
      substituted anilines in solid state under base- and solvent-free conditions
      against traditional synthetic routes. The initial formations of electron donor
      acceptor (EDA) adduct between DCNQ and aniline was found to be the driving force
      for the substitution reaction to occur in solid phase.

PMID- 22981515
TI  - Recurrent endobronchial diffuse large B-cell lymphoma. Diagnosed by cryoprobe.
AB  - The bronchial involvement of diffuse large B-cell lymphoma (DLBCL) is an
      exceptional finding. Histological diagnosis is done with lung tissue samples. In
      these cases, the need for immunohistochemistry studies in order to establish the
      diagnosis requires obtaining tissue samples of adequate size and quality.
      Sometimes, endoscopic explorations may be repeated to obtain further biopsies. We
      present the first documented case of recurrent endobronchial DLBCL that was
      diagnosed from a bronchial biopsy taken with a cryoprobe.

PMID- 22981516
TI  - Passed without a stroke: a UK mixed method study exploring student nurses'
      knowledge of stroke.
AB  - AIMS AND OBJECTIVES: To evaluate third year student nurses' knowledge and
      experiences of stroke education. To identify how student nurses can develop their
      understanding of stroke and its application to clinical nursing practice.
      BACKGROUND: Stroke is an international health issue and a major cause of
      morbidity and mortality in many countries throughout the world. Nurses have a
      significant role to play in reducing death and disability in people who have
      suffered a stroke and it has been suggested that some nurses may not be
      educationally prepared to meet the challenges of this complex condition. DESIGN:
      This evaluative study was based on a mixed method evaluative design. These
      quantitative and qualitative approaches involved the implementation of focus
      groups and questionnaires. METHOD: The following outcomes were measured during
      students' final year of their nursing studies: students' profiles and an
      assessment of students' knowledge of stroke. RESULTS: There was a mixed picture
      of student nurses' knowledge of stroke; a lack of awareness of some fundamental
      aspects of stroke including common symptoms, complications, risk factors and the
      long term treatment. Reassuringly, students expressed decisively the importance
      for nurses to be equipped with a sound foundation of stroke knowledge for
      clinical practice. CONCLUSIONS: All nursing students should have experience of
      being in contact with people who have had a stroke - and at present this does not
      always happen. A national intervention study is now suggested with a view to
      providing stroke education which is proportionate to its significance as a major
      health issue. RELEVANCE TO CLINICAL PRACTICE: Nurses draw upon their fundamental
      clinical skills to care and treat patients who have survived a stroke.
      Additionally, stroke survivors also require enhanced knowledge and this is
      recognised in the growth of specialist stroke nurses. Improving stroke mortality
      and morbidity is the responsibility of all of us involved in nurse education -
      introducing creative evaluative interventions could hold the most promising way
      forward.

PMID- 22981517
TI  - A mixed methods study to develop and pilot a competency assessment tool to
      support midwifery care of women with intellectual disabilities.
AB  - BACKGROUND: Recent reports have highlighted the poor quality of health care
      received by people with intellectual disabilities (otherwise known as 'learning
      disabilities') in the United Kingdom (UK). UK Confidential Enquiries into
      maternal deaths have highlighted adverse pregnancy outcomes for women with
      intellectual disabilities and need for timely and appropriate clinical care.
      OBJECTIVES: To develop and test a competency assessment tool to support midwifery
      care of women with intellectual disabilities. DESIGN: A mixed methods study.
      SETTING: Large inner city maternity unit. PARTICIPANTS: Midwives and key experts
      in intellectual disabilities, maternity policy and midwifery education. METHODS:
      Phase one comprised a systematic narrative review of the literature. Evidence
      identified informed phase two which included focus groups and interviews.
      Emergent themes informed the development of a competency assessment tool which
      was piloted in phase three. RESULTS: Phase one: Four primary research papers and
      two systematic reviews met the review inclusion criteria. Support to develop
      parenting skills of women with intellectual disabilities was highlighted as was
      the need to optimise organisation of maternity services. No studies specifically
      considered midwifery competencies to support women with intellectual
      disabilities. Phase two: 23 midwives attended three focus groups and individual
      interviews were conducted with national leaders in intellectual disability (n=6)
      and midwifery policy and education (n=7). Themes identified included need for
      individualised care provided by a known midwife, the importance of effective
      communication skills and need for clear knowledge and understanding of the
      legislative framework relevant to intellectual disability. Phase three: A
      convenience sample of 60 midwives was asked to participate in a pilot study to
      test the tool, 46 (77%) of whom responded. Thirty midwives (65%) felt competent
      in their ability to recognise intellectual disability and 37 (80%) competent or
      expert in understanding women have the right to be offered choice and make
      informed decisions. A high proportion (n=40, 87%) reported little or no knowledge
      regarding consent issues. CONCLUSION: Work to inform timely and appropriate care
      of women with intellectual disability has been neglected in the UK maternity
      services. Use of a tool could aid assessment of midwifery competencies to support
      women with intellectual disability and highlight where further midwifery
      education and development are needed. Evidence of optimal care for women with
      intellectual disabilities and their families across the continuum of pregnancy
      and birth is required.

PMID- 22981518
TI  - Morphological changes in the crown of mandibular molars with an additional
      distolingual root.
AB  - OBJECTIVE: The mandibular molars typically have two roots placed mesiodistally,
      but they occasionally have an additional distolingual (DL) root. This study was
      to determine the morphological characteristics of the crown of such mandibular
      molars. DESIGN: Radiographic records and study models were collected from a
      Korean population (n=86 patients). Each molar was assigned to either the
      experimental group (i.e. with a DL root) or the control group (i.e. without a DL
      root; n=41 patients) based on the radiographic findings. The intercuspal
      distances of the first permanent molars (total, n=100; control/experimental,
      n=50/50) and primary second molars (46, 23/23), and the largest
      buccolingual/mesiodistal widths of those molars and primary first molars (42,
      21/21) were measured for molars with and without a DL root. In addition, the
      correlation between the existence of a sixth cusp and a DL root was examined.
      RESULTS: The crowns of first permanent and primary second molars with DL roots
      had significantly larger intercuspal distances between the distobuccal
      distolingual cusp tips and a larger distal-area buccolingual width than those
      without the DL root (t-test; p<0.05). There was no significant correlation
      between the existence of a sixth cusp and the presence of a DL root. CONCLUSIONS:
      The existence of a DL root was associated with larger buccolingual dimensions,
      especially in the distal area.

PMID- 22981519
TI  - [Kearns-Sayre syndrome: a case report].
AB  - Kearns-Sayre syndrome (KSS), first described in 1958, is a multisystem disease
      defined by a characteristic triad of progressive external ophthalmoplegia,
      pigmentary retinopathy and atrioventricular block. These signs are frequently
      associated with increased cerebrospinal fluid protein level and cerebellar
      ataxia. This syndrome is caused by deletions in mitochondrial DNA, the age of
      onset is generally below 20, and the degree of severity differs between patients,
      as well as the prognosis, which may be fatal. The ocular manifestations include:
      bilateral ptosis, progressive external ophthalmoplegia and atypical pigmentary
      retinopathy. By way of this case report, the authors discuss the epidemiologic,
      clinical and therapeutic aspects of KSS, including the difficulty in managing
      ptosis in these cases.

PMID- 22981520
TI  - [Distribution of central corneal thickness in a melanoderm population].
AB  - PURPOSE: To describe characteristics of central corneal thickness in a defined
      melanoderm population. PATIENTS AND METHODS: A retrospective study was performed
      on patients with and without glaucoma followed on the ophthalmology service of
      Tokoin teaching hospital in Lome from January to September 2005. All subjects
      underwent central corneal thickness measurement by ultrasonic pachymetry between
      8:00 and 11:00 am by the same operator. RESULTS: A total of 1205 subjects (609
      men and 596 women) were included in the study, corresponding to 2410 eyes. The
      participants were 3 to 85years old. Mean central corneal thickness was 532.94+/
      34.82MUm for the entire population, 532.56+/-36.25MUm for the right eye, 533.44+/
      35.96MUm for the left eye, 536.38+/-34.67MUm in men and 529.41+/-34.64MUm in
      women. Central corneal thickness was greater (542.94MUm) in the 6- to 10-year-old
      group and gradually decreased after 35years. CONCLUSION: Melanoderm subjects have
      thinner central corneas, which may be related to the higher prevalence of ocular
      hypertension and glaucoma in our populations. Incorporation of corneal pachymetry
      with intraocular pressure measurements is essential in the early management of
      ocular hypertension and glaucoma, particularly in melanoderm subjects.

PMID- 22981521
TI  - [Results of scleral buckling for rhegmatogenous retinal detachment in phakic
      eyes].
AB  - PURPOSE: To report the results of primary scleral buckling in the treatment of
      uncomplicated rhegmatogenous retinal detachment in phakic eyes and to determine
      risk factors for failure. PATIENTS AND METHODS: Retrospective study of 100
      consecutive phakic eyes undergoing surgery for uncomplicated retinal detachment.
      All patients underwent cryopexy, scleral buckling with hard silicone explant type
      287 and in selected cases, drainage of subretinal fluid and gas tamponnade with
      air or SF6. RESULTS: The primary anatomic success rate was 84% and 99%
      respectively after one or multiple procedures. The causes of failure were new
      breaks (50%), proliferative vitreoretinopathy (31.2%) and malposition of the
      scleral buckle (18.8%). Mean visual acuity improved from 0.77+/-0.75 logMar to
      0.21+/-0.19 logMar (P<0.00001). Predictive risk factors for failure included
      extent of the detachment beyond one quadrant and multiple breaks (P=0.03).
      Horseshoe tears had a worse prognosis than oral dialysis or atrophic round holes
      (P=0.04). CONCLUSION: Scleral buckling remains safe and effective for the
      treatment of uncomplicated rhegmatogenous retinal detachments in phakic eyes,
      especially when the extent of the detachment was less than one quadrant or in the
      presence of a single tear, an atrophic round hole or an oral dialysis.

PMID- 22981522
TI  - [Ocular involvement in polyarteritis nodosa: two cases].
AB  - INTRODUCTION: Polyarteritis nodosa (PAN) is a systemic vasculitis with
      polymorphic manifestations. Ocular involvement is rare; we report two such cases.
      CASES: The first case was a 56-year-old man with PAN treated with
      corticosteroids. A year and a half later, during a disease outbreak associated
      with decreased visual acuity, ocular examination objectified a localized pigment
      epithelial detachment in the right eye. The outcome was favorable with corticoid
      bolus followed by azathioprine. The second case was a 41-year-old man presenting
      with PAN and decreased visual acuity. Ophthalmologic examination showed
      inferotemporal branch vein occlusion in the right eye with serous retinal
      detachments in the left eye. The outcome was favorable with intravenous
      cyclophosphamide followed by azathioprine. DISCUSSION: The incidence of ocular
      involvement in PAN varies from 10 to 20%. It is most often associated with
      vasculitis of retinal and choroidal arteries. Fluorescein angiography is the gold
      standard of diagnosis. Multifocal acute ischemia of the choriocapillaris is very
      pathognomonic. Immunosuppressant drugs are effective and should be reserved for
      severe forms.

PMID- 22981523
TI  - [Acute sectoral choroidal ischemia: a case report].
AB  - Sectoral choroidal ischemia is a classic sign of giant cell arteritis, although
      the latter is more typically associated with anterior ischemic optic neuropathy
      or central retinal artery occlusion. We report the case of an acute choroidal
      ischemia in a 68-year-old, one-eyed patient, who presented with deterioration of
      visual acuity and metamorphopsia in his left eye (his right eye was counting
      fingers due to high myopia). Fundus examination revealed retinal pigment
      epithelium (RPE) alterations and slow choroidal perfusion on fluorescein
      angiography. Macular Optical Coherence Tomography (OCT) showed a total disruption
      of the photoreceptor layer. Although prompt corticosteroid therapy preserved some
      vision, secondary macular retinal pigment epithelial changes limited the visual
      outcome. No other ophthalmological signs were observed in follow-up.

PMID- 22981524
TI  - [Demographic evolution of acute primary angle closure between 2001-2003 and 2008
      2010: impact of modern cataract surgery].
AB  - PURPOSE: To study the demographic evolution of acute primary angle closure.
      MATERIALS AND METHODS: Retrospective study of patients with acute primary angle
      closure treated between 2001-2003 and 2008-2010. For each period, a comparison
      was made of demographic data (number of cases, age at diagnosis, sex), clinical
      data (biometry, presence or absence of iris plateau or cataract) and therapeutic
      data (iridotomy, phacoemulsification, trabeculectomy). RESULTS: Fifty-two cases
      of acute primary angle closure were treated in the University Hospital of Nantes,
      France: 34 eyes in 2001-2003 and 18 in 2008-2010, representing a decrease of 47%
      in acute primary angle closure cases in 7years. The incidence of acute primary
      angle closure attacks significantly decreased from 0.0596% in 2001-2003 to
      0.0224% in 2008-2010. Acute angle closure attacks secondary to cataract decreased
      significantly from 82% in 2001-2003 to 50% in 2008-2010. In cataractous cases
      with ocular hypertension persisting after peripheral iridotomy, cataract
      extraction was performed. Early phacoemulsification less than 10days was
      significantly more common in 2008-2010 than in 2001-2003 (40% versus 10%).
      CONCLUSION: This study confirms the recent decrease in acute primary angle
      closure attacks. The consistent increase in cataract surgery in the elderly has
      probably played a preventive role, since the highest decrease in acute primary
      angle closure cases was observed among the 70-80-year-old population. Recently,
      acute primary angle closure cases are less often due to cataract than to primary
      pupillary block or iris plateau. The prevention of acute primary angle closure by
      gonioscopic monitoring in patients at risk is indispensable.

PMID- 22981525
TI  - [Ballistic trauma resulting in carotid-cavernous fistula].
AB  - Post-traumatic carotid-cavernous fistula is an abnormal communication between the
      internal carotid artery in its intracavernous portion and the cavernous sinus,
      resulting from a tear in the arterial wall connecting the internal carotid artery
      with the cavernous sinus. Direct gunshot trauma is unusual. Clinically, the
      symptoms most often include a classic triad: red eye, chemosis and proptosis.
      Cross-sectional imaging including CT angiography allows for positive diagnosis by
      showing pathognomonic signs. Arteriography remains the procedure of choice for
      proper mapping of the lesion and accurate specification of the type of fistula,
      and at the same time serves as a means of embolization.

PMID- 22981526
TI  - [Epidemiological aspects of keratoconus in children].
AB  - PURPOSE: To study the epidemiological aspects of keratoconus in children.
      METHODS: We conducted a retrospective study of patients with keratoconus
      diagnosed prior to age 15 or after age 27. Age, gender, reason for consultation,
      ethnicity, personal and family history, allergic history, eye rubbing, optical
      and surgical treatment, and educational and professional background were
      identified. Data from each group were compared by Chi(2) testing. RESULTS: Forty
      nine children and 167 adults were studied. The majority of patients were
      Caucasian. Children were more frequently male (P=0.0386) and allergic (67.35%
      versus 47.31% in adults, P=0.0136). Eye rubbing was found in 91.84% of children
      and 70.06% of adults (P=0.002). In total, 12.24% of children had a family history
      of keratoconus versus 14.97% of adults (P=0.6324). Totally, 68.09% of children
      were fitted with rigid contact lenses versus 15.66% of adults (P=0.0909). In all,
      80.5% of surgically treated children underwent corneal collagen cross-linking
      versus 30% of adults. DISCUSSION: Younger patients are more often male, with
      women being older at time of diagnosis. Allergy is a frequent association.
      However, 25% of children in the general population display allergies. In any
      event, eye rubbing is a common feature, whether due to itching or induced
      ametropia. CONCLUSION: In order to detect the disease early, corneal topography
      could be performed routinely in all young, allergic boys with a history of eye
      rubbing and recent-onset corneal astigmatism.

PMID- 22981527
TI  - Calculation of the capnographic index based on expiratory molar mass-volume
      curves--a suitable tool to screen for cystic fibrosis lung disease.
AB  - BACKGROUND: Volumetric capnography reflecting the course of CO2-exhalation is
      used to assess ventilation inhomogeneity. Calculation of the slope of expiratory
      phase 3 and the capnographic index (KPIv) from expirograms allows quantification
      of extent and severity of small airway impairment. However, technical limitations
      have hampered more widespread use of this technique. Using expiratory molar mass
      volume-curves sampled with a handheld ultrasonic flow sensor during tidal
      breathing is a novel approach to extract similar information from expirograms in
      a simpler manner possibly qualifying as a screening tool for clinical routine.
      The aim of the present study was to evaluate calculation of the KPIv based on
      molar mass-volume-curves sampled with an ultrasonic flow sensor in patients with
      CF and controls by assessing feasibility, reproducibility and comparability with
      the Lung Clearance Index (LCI) derived from multiple breath washout (MBW) used as
      the reference method. METHODS: Measurements were performed in patients with CF
      and healthy controls during a single test occasion using the EasyOne Pro, MBW
      Module (ndd Medical Technologies, Switzerland). RESULTS: Capnography and MBW were
      performed in 87/96 patients with CF and 38/42 controls, with a success rate of
      90.6% for capnography. Mean age (range) was 12.1 (4-25) years. Mean (SD) KPIv was
      6.94 (3.08) in CF and 5.10 (2.06) in controls (p=0.001). Mean LCI (SD) was 8.0
      (1.4) in CF and 6.2 (0.4) in controls (p=<0.001) and correlated significantly
      with the KPIv (p=<0.001). CONCLUSION: Calculation of the KPIv based on molar mass
      volume-curves is feasible. KPIv is significantly different between patients with
      CF and controls and correlates with the LCI. However, individual data revealed a
      relevant overlap between patients and controls requiring further evaluation,
      before this method can be recommended for clinical use.

PMID- 22981528
TI  - Hematopoietic stem and progenitor cell populations in MoMuLV-ts-1 induced
      lymphoma in a murine model.
AB  - During self-renewal of the hematopoietic stem cells there is a potential for
      these new cells to develop into abnormal malignant cells due to environmental,
      chemical or microbial challenges. This may lead to blood malignancies, including
      leukemia and lymphoma. Our laboratory was the first to develop a mouse model to
      study the development of lymphoma among pups of retrovirus infected mothers. We
      have established that if the newborn pups suckle breast milk from the mothers
      infected with a temperature sensitive Moloney Murine Leukemia Virus (MoMuLV-ts1),
      they develop lymphoma. Stem and progenitor cell populations were determined from
      blood, spleen, and thymus samples in infected mice with and without lymphoma
      using flow cytometry and specific protein markers, including CD117+/CD34+;
      CD117+/Sca-1+; CD135+/Sca-1+; Ter119+/CD71+ and CD117+/CD45+. Some stem cell
      populations were increased in infected mice with lymphoma. These stem cells
      appear to be involved in the development of lymphoma in our mouse model.

PMID- 22981529
TI  - Elevated plasma fibrinogen, psychological distress, antidepressant use, and
      hospitalization with depression: two large population-based studies.
AB  - OBJECTIVES: Low-grade systemic inflammation may contribute to the development of
      depression. We tested the hypothesis that elevated plasma levels of the
      inflammatory marker fibrinogen are associated with psychological distress, use of
      antidepressant medication, and with hospitalization with depression in the
      general population. METHODS: We examined 73,367 20-100 year old men and women
      from two large population-based studies, the Copenhagen General Population Study
      and the Copenhagen City Heart Study. We measured plasma fibrinogen and recorded
      symptoms of psychological distress, use of antidepressant medication, and
      hospitalization with depression in both cross-sectional and prospective studies.
      RESULTS: In cross-sectional analyses, a stepwise increase in fibrinogen
      percentile categories was associated with a stepwise increase in risk of
      psychological distress, use of antidepressant medication, and hospitalization
      with depression (p-trend 2*10(-11) to 5*10(-95)). Furthermore, when different
      classes of antidepressant medication were examined, a stepwise increase in
      fibrinogen percentile categories was associated with a stepwise increase in risk
      of use of Selective Serotonin Reuptake Inhibitors and Tricyclic Antidepressants
      (p-trend 7*10(-18) and 6*10(-7), respectively). In prospective analyses, stepwise
      increasing fibrinogen percentile categories also associated with stepwise
      increasing risk of hospitalization with depression (p-trend=7*10(-6)): age and
      gender adjusted hazard ratios were 1.13 (95% confidence interval 0.70-1.83) for
      the 25.1-50th percentiles, 1.53 (0.97-2.42) for the 50.1-75th percentiles, 1.82
      (1.11-2.97) for the 75.1-90th percentiles, 2.10 (1.12-3.95) for the 90.1-95th
      percentiles, and 3.23 (1.79-5.85) for the >95th percentiles, versus the 0-25th
      percentiles. CONCLUSION: Elevated levels of fibrinogen were associated with
      psychological distress, use of antidepressant medication, and with
      hospitalization with depression in 73,367 individuals from the general
      population, in cross-sectional studies and in prospective studies for
      hospitalization with depression.

PMID- 22981530
TI  - A critical appraisal of the accuracy of the RIFLE and AKIN classifications in
      defining "acute kidney insufficiency" in critically ill patients.
AB  - PURPOSE: The lack of a consensus definition for acute kidney injury (AKI) has led
      to a great deal of discrepancies and confusion in the literature in this field.
      Thus, the RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure of
      kidney function, Loss of kidney function and End-stage renal disease) and Acute
      Kidney Injury Network (AKIN) classifications were developed by multidisciplinary
      collaborative groups and were validated by experts in an international consensus
      conference in 2007 under an umbrella "acute kidney insufficiency" definition.
      METHODS: Search in the MEDLINE and PUBMED databases for relevant literature from
      January 2000 to June 2011 was performed to assess the accuracy of the novel
      consensus definitions for AKI. CONCLUSIONS: Both systems are based on serum
      creatinine level and urine output criteria and are staged in 3 severity levels. A
      major difference between these 2 classifications is that smaller and more rapid
      changes in serum creatinine are considered in the AKIN stage 1. Each AKI
      classification has demonstrated its ability to stratify patients according to
      their AKI severity and to predict outcomes. No classification system has been
      shown to be superior over the others. Their application in clinical studies would
      benefit from standardization and the new Kidney Disease Improving Global Outcomes
      definition of AKI was recently proposed to achieve this aim. Because these
      classifications do not allow earlier AKI diagnosis and do not optimize the timing
      of RRT initiation, they remain of moderate utility from the patient's point of
      view.

PMID- 22981531
TI  - Interstitial cortisol obtained by microdialysis in mechanically ventilated septic
      patients: correlations with total and free serum cortisol.
AB  - PURPOSE: The aim of this study was to measure subcutaneous tissue cortisol
      obtained by microdialysis (MD) in 35 mechanically ventilated septic patients.
      MATERIALS AND METHODS: Upon intensive care unit admission, an MD catheter was
      inserted into the subcutaneous tissue of the thigh. Cortisol (CORT) was
      determined in a 5:00 to 9:00 am microdialysate sample collected within 72 hours.
      Concurrently, serum total (T-CORT) and free CORT (F-CORT) were measured. The
      Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ
      Failure Assessment scores were calculated. Both T-CORT less than 10 MUg/dL and F
      CORT less than 0.8 MUg/dL were considered as indicating critical illness-related
      corticosteroid insufficiency. Adrenal adequacy was defined as T-CORT greater than
      20 MUg/dL or F-CORT greater than 2.0 MUg/dL. RESULTS: Total CORT correlated
      significantly with F-CORT (rs = +0.8, P < .0001). Microdialysis CORT had a lower
      correlation with T-CORT (rs = +0.6, P < .0001) and F-CORT (rs = +0.7, P < .0001)
      and a weak correlation with APACHE II score (rs = +0.4, P < .01). On the basis of
      MD-CORT, the patients were divided in quartiles. Although the median F-CORT and T
      CORT levels were significantly different (P < .001) among the MD-CORT quartiles,
      there was a considerable overlap between the subgroups. All patients with T-CORT
      less than 10 MUg/dL and all but 3 patients with F-CORT less than 0.8 MUg/dL had
      tissue CORT in the lower quartile. However, only 50% and 58% of patients with
      adequate T-CORT and F-CORT levels, respectively, had concordant MD-CORT in the
      highest quartile. CONCLUSIONS: Microdialysis CORT levels correlate moderately
      with circulating T-CORT and F-CORT. Of note, several patients presented with
      discrepant measurements between interstitial and circulating CORT concentrations.
      Thus, interstitial CORT measurements represent an additional tool to investigate
      the tissue CORT availability in critically ill patients.

PMID- 22981532
TI  - Barriers to feeding critically ill patients: a multicenter survey of critical
      care nurses.
AB  - PURPOSE: The aims of this study were to describe the barriers to enterally
      feeding critically ill patients from a nursing perspective and to examine whether
      these barriers differ across centers. MATERIALS AND METHODS: A cross-sectional
      survey was conducted in 5 hospitals in North America. A 45-item questionnaire was
      administered to critical care nurses to evaluate the barriers to enterally
      feeding patients. RESULTS: A total of 138 of 340 critical care nurses completed
      the questionnaire (response rate of 41%). The 5 most important barriers to nurses
      were as follows: (1) other aspects of patient care taking priority over
      nutrition, (2) not enough feeding pumps available, (3) enteral formula not
      available on the unit, (4) difficulties in obtaining small bowel access in
      patients not tolerating enteral nutrition, and (5) no or not enough dietitian
      coverage during weekends and holidays. For 18 (81%) of 22 potential barriers, the
      rated magnitude of importance was similar across the 5 intensive care units.
      CONCLUSION: Nurses in our multicenter survey identified important barriers to
      providing adequate enteral nutrition to their critically ill patients. The
      importance of these barriers does not appear to differ significantly across
      different clinical settings. Future research is required to evaluate if tailoring
      interventions to overcome these identified barriers is an effective strategy of
      improving nutrition practice.

PMID- 22981533
TI  - Nonpharmacologic interventions for prevention of catheter-related thrombosis: a
      systematic review.
AB  - PURPOSE: The aim of this study was to summarize randomized controlled trials
      (RCTs) of nonpharmacologic interventions for prevention of catheter-related
      thromboses (CRTs). METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane Central
      Register of Controlled Trials were systematically searched for RCTs examining any
      nonpharmacologic intervention to prevent symptomatic or asymptomatic CRT. Titles
      and abstracts were screened by a single reviewer, followed by full-text screening
      by 2 independent reviewers. Data were extracted and quality assessed by a single
      analyst and audited by a second analyst. Strength of the evidence for each
      intervention was assessed using the Grading of Recommendations Assessment,
      Development and Evaluation. RESULTS: Ten RCTs enrolling 1,378 patients were
      included. Moderate- to high-quality evidence suggested peripherally inserted
      central catheters and insertion of central venous catheters (CVCs) at the femoral
      site increased CRT when compared with other catheter types or insertion sites,
      respectively. Evidence comparing CRT in CVCs inserted at the jugular vs the
      subclavian site as well as the placement of the CVC tip was of low quality and
      inconclusive. Low-quality evidence suggested that valved ports and silver-coated
      catheters had no effect on CRT. No RCT evidence was identified for other
      interventions. CONCLUSIONS: Peripherally inserted central catheters and femoral
      insertion of CVCs should be avoided if possible. Randomized controlled trials are
      needed to ascertain the effects of other nonpharmacologic interventions to
      prevent CRT.

PMID- 22981534
TI  - Do-not-resuscitate order: a view throughout the world.
AB  - Resuscitation has the ability to reverse premature death. It can also prolong
      terminal illness, increase discomfort, and consume resources. The do-not
      resuscitate (DNR) order and advance directives are still a debated issue in
      critical care. This review will focus on several aspects, regarding withholding
      and/or withdrawing therapies and advance directives in different continents. It
      is widely known that there is a great diversity of cultural and religious beliefs
      in society, and therefore, some critical ethical and legal issues have still to
      be solved. To achieve a consensus, we believe in the priority of continuing
      education and training programs for health care professionals. It is our opinion
      that a serious reflection on ethical values and principles would be useful to
      understand the definition of medical professionalism to make it possible to
      undertake the best way to avoid futile and aggressive care. There is evidence of
      the lack of DNR order policy worldwide. Therefore, it appears clear that there is
      a need for standardization. To improve the attitude about the DNR order, it is
      necessary to achieve several goals such as: increased communication, consensus on
      law, increased trust among patients and health care systems, and improved
      standards and quality of care to respect the patient's will and the family's
      role.

PMID- 22981535
TI  - Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for
      natural helper cell development and allergic inflammation.
AB  - Natural helper (NH) cells are innate lymphoid cells (ILCs) that produce T helper
      2 (Th2)-cell-type cytokines in the lung- and gut-associated lymphoid tissues.
      Currently, the lineage relationship between NH cells in different tissues and
      between NH cells and interleukin-22 (IL-22)-producing retinoic-acid-receptor
      related orphan receptor (ROR)gammat-positive ILCs is unclear. Here, we report
      that NH cells express RORalpha, but not RORgammat. RORalpha-deficient, but not
      RORgammat-deficient, mice lacked NH cells in all tissues, whereas all other
      lymphocytes, including RORgammat(+) ILCs, were unaffected. NH-cell-deficient mice
      generated by RORalpha-deficient bone-marrow transplantation had normal Th2 cell
      responses but failed to develop acute lung inflammation in response to protease
      allergen, thus confirming the essential role of NH cells in allergic lung
      inflammation. We have also identified RORalpha-dependent NH cell progenitors in
      the bone marrow. Thus, all NH cells belong to a unique RORalpha-dependent cell
      lineage separate from other lymphoid cell lineages.

PMID- 22981536
TI  - Cell volume regulation modulates NLRP3 inflammasome activation.
AB  - Cell volume regulation is a primitive response to alterations in environmental
      osmolarity. The NLRP3 inflammasome is a multiprotein complex that senses pathogen
      and danger-associated signals. Here, we report that, from fish to mammals, the
      basic mechanisms of cell swelling and regulatory volume decrease (RVD) are sensed
      via the NLRP3 inflammasome. We found that a decrease in extracellular osmolarity
      induced a K(+)-dependent conformational change of the preassembled NLRP3-inactive
      inflammasome during cell swelling, followed by activation of the NLRP3
      inflammasome and caspase-1, which was controlled by transient receptor potential
      channels during RVD. Both mechanisms were necessary for interleukin-1beta
      processing. Increased extracellular osmolarity prevented caspase-1 activation by
      different known NLRP3 activators. Collectively, our data identify cell volume
      regulation as a basic conserved homeostatic mechanism associated with the
      formation of the NLRP3 inflammasome and reveal a mechanism for NLRP3 inflammasome
      activation.

PMID- 22981537
TI  - The cytokines interleukin 27 and interferon-gamma promote distinct Treg cell
      populations required to limit infection-induced pathology.
AB  - Interferon-gamma (IFN-gamma) promotes a population of T-bet(+) CXCR3(+)
      regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology.
      Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T
      bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar
      population emerged that limited T cell responses and was dependent on IFN-gamma
      in the periphery but on IL-27 at mucosal sites. Transfer of Treg cells
      ameliorated the infection-induced pathology observed in Il27(-/-) mice, and this
      was dependent on their ability to produce IL-10. Microarray analysis revealed
      that Treg cells exposed to either IFN-gamma or IL-27 have distinct
      transcriptional profiles. Thus, IFN-gamma and IL-27 have different roles in Treg
      cell biology and IL-27 is a key cytokine that promotes the development of Treg
      cells specialized to control Th1 cell-mediated immunity at local sites of
      inflammation.

PMID- 22981540
TI  - Commentary on 'The best conditions for parallel stenting during EVAR: an in vitro
      study'.

PMID- 22981538
TI  - Adipose tissue invariant NKT cells protect against diet-induced obesity and
      metabolic disorder through regulatory cytokine production.
AB  - Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T
      cells that influence inflammatory responses. We have shown that iNKT cells,
      previously thought to be rare in humans, were highly enriched in human and murine
      adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were
      depleted, correlating with proinflammatory macrophage infiltration. iNKT cell
      numbers were restored in mice and humans after weight loss. Mice lacking iNKT
      cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin
      resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or
      in vivo activation of iNKT cells via their lipid ligand, alpha
      galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty
      liver and improved insulin sensitivity through anti-inflammatory cytokine
      production by adipose-derived iNKT cells. This finding highlights the potential
      of iNKT cell-targeted therapies, previously proven to be safe in humans, in the
      management of obesity and its consequences.

PMID- 22981539
TI  - Compromised intestinal epithelial barrier induces adaptive immune compensation
      that protects from colitis.
AB  - Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit
      enhanced intestinal epithelial permeability, bacterial translocation, and
      elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate
      the contribution of adaptive immune compensation in response to increased
      intestinal epithelial permeability, we examined the susceptibility of F11r(-/
      )Rag1(-/-) mice to acute colitis. Although negligible contributions of adaptive
      immunity in F11r(+/+)Rag1(-/-) mice were observed, F11r(-/-)Rag1(-/-) mice
      exhibited increased microflora-dependent colitis. Elimination of T cell subsets
      and cytokine analyses revealed a protective role for TGF-beta-producing CD4(+) T
      cells in F11r(-/-) mice. Additionally, loss of JAM-A resulted in elevated mucosal
      and serum IgA that was dependent upon CD4(+) T cells and TGF-beta. Absence of IgA
      in F11r(+/+)Igha(-/-) mice did not affect disease, whereas F11r(-/-)Igha(-/-)
      mice displayed markedly increased susceptibility to acute injury-induced colitis.
      These data establish a role for adaptive immune-mediated protection from acute
      colitis under conditions of intestinal epithelial barrier compromise.

PMID- 22981541
TI  - Transcriptional regulation of human novel gene SPATA12 promoter by AP-1 and HSF.
AB  - Human SPATA12 is a spermatogenesis associated gene and is supposed to function as
      an inhibitor during male germ cell development. SPATA12 is specifically expressed
      in spermatocytes, spermatids, and spermatozoa of human testis. In order to
      understand the regulation mechanism of SPATA12 gene expression, we identified and
      characterized the SPATA12 gene core promoter region and transcription factor
      binding sites by using reporter gene assays. AP-1 is founded to be a potential
      transcriptional activator of SPATA12. The promoter activity of SPATA12 was
      drastically declined after AP-1 binding site mutation or deletion. We also
      demonstrated that AP-1 combined with Smad3/4 contributes to the transcriptional
      regulation of SPATA12 in response to TGF-beta1. The expression of SPATA12 could
      be induced by TGF-beta1 in a dose-dependent manner, suggesting that AP-1 as an
      activator plays a role in the regulation of SPATA12 promoter. We have also shown
      that heat shock treatment could activate the expression of SPATA12 and
      transcription factor HSF binding sites in the SPATA12 promoter might be
      responsible for this heat-induction. These results suggested that AP-1 and HSF
      may play an important role in regulating SPATA12 promoter activity.

PMID- 22981542
TI  - Exploratory data analysis for the interpretation of low template DNA mixtures.
AB  - The interpretation of DNA mixtures has proven to be a complex problem in forensic
      genetics. In particular, low template DNA samples, where alleles can be missing
      (allele drop-out), or where alleles unrelated to the crime-sample are amplified
      (allele drop-in), cannot be analysed with classical approaches such as random man
      not excluded or random match probability. Drop-out, drop-in, stutters and other
      PCR-related stochastic effects, create uncertainty about the composition of the
      crime-sample, making it difficult to attach a weight of evidence when (a)
      reference sample(s) is (are) compared to the crime-sample. In this paper, we use
      a probabilistic model to calculate likelihood ratios when there is uncertainty
      about the composition of the crime-sample. This model is essentially exploratory
      in the sense that it allows the exploration of LRs when two key-parameters, drop
      out and drop-in are varied within their plausible ranges of variation. We build
      on the work of Curran et al., and improve their probabilistic model to allow more
      flexibility in the way the model parameters are applied. Two new main
      modifications are brought to their model: (i) different drop-out probabilities
      can be applied to different contributors, and (ii) different parameters can be
      used under the prosecution and the defence hypotheses. We illustrate how the LRs
      can be explored when the drop-out and drop-in parameters are varied, and suggest
      the use of Monte Carlo simulations to derive plausible ranges for the probability
      of drop-out. Although the model is suited for both high and low template samples,
      we illustrate the advantages of the exploratory approach through two DNA mixtures
      (involving two and at least three individuals) with low template components.

PMID- 22981543
TI  - Hepatic lipase activity is decreased in Japanese patients with type III
      hyperlipoproteinemia.
AB  - BACKGROUND: Type III hyperlipoproteinemia (HLP), a disorder associated with a
      high incidence of premature cardiovascular diseases, is characterized by the
      accumulation of remnant lipoproteins in the plasma. The primary genetic defect in
      patients with type III HLP is the presence of apolipoprotein E2 (apoE2), an
      isoform of apoE, and accumulation of remnant lipoproteins in the plasma has been
      thought to be attributable to the presence of apoE2, which bind poorly to low
      density lipoprotein receptors, resulting in defective remnant lipoprotein
      clearance. On the other hand, the activity of hepatic lipase (HL), the enzyme
      that plays a pivotal role in the removal of remnant lipoproteins, in type III HLP
      has not been investigated. METHODS: We examined post-heparin plasma lipoprotein
      lipase (LPL) and HL activities in 7 patients with type III HLP. The activities of
      HL and LPL in post-heparin plasma were measured separately by an immunochemical
      method using antiserum specifically directed against HL. RESULTS: The post
      heparin plasma HL activity was significantly reduced, while the LPL activity was
      normal. CONCLUSIONS: Reduced HL activity may account, at least in part, for the
      accumulation of remnant lipoproteins in the plasma, a characteristic feature of
      type III HLP.

PMID- 22981544
TI  - Successful salvage reimplantation of penile prosthesis after reservoir erosion
      into continent urinary reservoir.

PMID- 22981545
TI  - Training in clinical oncology: results of the Royal College of Radiologists'
      survey of new consultants.
AB  - AIMS: To seek the views of consultants appointed less than 2 years ago on the
      appropriateness of their training in fitting them to carry out their present
      posts, the FRCR examination, experience of research and the prevalence and value
      of out of programme experience and acting up as a consultant. MATERIALS AND
      METHODS: All the consultants identified from the Royal College of Radiologists'
      database as having been appointed to a consultant post in the last 2 years were
      emailed inviting them to take part in a web-based survey. RESULTS: The response
      rate was 60% (32 of 53 consultants). Ninety-four per cent agreed or strongly
      agreed that training had equipped them for clinical work as a consultant, but
      only 44% agreed or strongly agreed that training had equipped them to fulfil the
      management roles. Free text answers stressed the importance of management skills,
      getting involved with trial set-up and producing publications early in their
      career. Ninety-four per cent agreed or strongly agreed that they had adequate
      opportunity to develop skills in systemic therapy and radiotherapy planning, but
      only 56% thought this was the case for intensity-modulated radiotherapy and image
      guided radiotherapy. Although 87% agreed or strongly agreed they had sufficient
      opportunity to develop teaching skills, this was only the case in 62% with regard
      to research skills. They published a median number of three papers in peer
      reviewed journals. Twenty-five per cent of respondents studied for research
      degrees; 69% of consultants had undertaken out of programme experience and 50%
      had acted up as a consultant and these were generally found to be valuable
      experiences. There was strong support for the FRCR examination. CONCLUSIONS:
      Consultants appointed in the last 2 years are generally satisfied with their
      training. Training in intensity-modulated radiotherapy and image-guided
      radiotherapy should be improved and the advanced specialist training requires
      reviewing to better fit consultants for subspecialisation, management and
      research.

PMID- 22981546
TI  - Epithelial mesenchymal transition in colorectal cancer: Seminal role in promoting
      disease progression and resistance to neoadjuvant therapy.
AB  - BACKGROUND: Epithelial mesenchymal transition (EMT) may be physiological as part
      of embryological development, or pathological as part of cancer development. It
      is one of the key initiating events in the metastatic cascade. EMT has profound
      effects on tumour cell invasiveness, proliferation and motility. In the present
      article we aimed to review the potential role of EMT as a process to explain
      colorectal cancer progression and resistance to neoadjuvant therapy. METHODS:
      Extensive literature searches were performed in Pubmed, EMBASE and Google Scholar
      databases to identify relevant articles published before March 2012. RESULTS:
      There is adequate evidence to support the complex upstream signalling alterations
      needed for EMT to occur in colorectal cancers. Changes of EMT are likely to be
      found at the tumour invasive front: the deepest, growing tumour margin. Loss of E
      cadherin at the cell membrane causes loss of cellular integrity, with subsequent
      migration of malignant cells and tumour budding. These processes are associated
      with metastases and recurrence of colorectal cancer. There is early evidence from
      a limited number of studies that resistance to neoadjuvant therapy in colorectal
      cancer is associated with changes of EMT. However, there is a lack of supporting
      evidence originating from human colorectal cancer tissues. CONCLUSIONS: Emerging
      evidence demonstrates that development of EMT in colorectal cancer leads to an
      aggressive phenotype that may promote metastatic spread, and augment treatment
      resistance during neoadjuvant therapy. A clearer understanding of the processes
      and role of EMT in colorectal cancer may also highlight novel therapeutic
      strategies.

PMID- 22981547
TI  - Cost-effectiveness and clinical effectiveness of catheter-based renal denervation
      for resistant hypertension.
AB  - OBJECTIVES: The purpose of this study was to assess cost-effectiveness and long
      term clinical benefits of renal denervation in resistant hypertensive patients.
      BACKGROUND: Resistant hypertension affects 12% of hypertensive persons. In the
      Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation
      (RDN) lowered systolic blood pressure by 32 +/- 23 mm Hg from 178 +/- 18 mm Hg at
      baseline. METHODS: A state-transition model was used to predict the effect of RDN
      and standard of care on 10-year and lifetime probabilities of stroke, myocardial
      infarction, all coronary heart disease, heart failure, end-stage renal disease,
      and median survival. We adopted a societal perspective and estimated an
      incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life
      year, both discounted at 3% per year. Robustness and uncertainty were evaluated
      using deterministic and probabilistic sensitivity analyses. RESULTS: Renal
      denervation substantially reduced event probabilities (10-year/lifetime relative
      risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart
      disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81).
      Median survival was 18.4 years for RDN versus 17.1 years for standard of care.
      The discounted lifetime incremental cost-effectiveness ratio was $3,071 per
      quality-adjusted life-year. Findings were relatively insensitive to variations in
      input parameters except for systolic blood pressure reduction, baseline systolic
      blood pressure, and effect duration. The 95% credible interval for incremental
      cost-effectiveness ratio was cost-saving to $31,460 per quality-adjusted life
      year. CONCLUSIONS: The model suggests that catheter-based renal denervation, over
      a wide range of assumptions, is a cost-effective strategy for resistant
      hypertension that might result in lower cardiovascular morbidity and mortality.

PMID- 22981548
TI  - Hospital patterns of use of positive inotropic agents in patients with heart
      failure.
AB  - OBJECTIVES: This study sought to determine hospital variation in the use of
      positive inotropic agents in patients with heart failure. BACKGROUND: Clinical
      guidelines recommend targeted use of positive inotropic agents in highly selected
      patients, but data are limited and the recommendations are not specific. METHODS:
      We analyzed data from 376 hospitals including 189,948 hospitalizations for heart
      failure from 2009 through 2010. We used hierarchical logistic regression models
      to estimate hospital-level risk-standardized rates of inotrope use and risk
      standardized in-hospital mortality rates. RESULTS: The risk-standardized rates of
      inotrope use ranged across hospitals from 0.9% to 44.6% (median: 6.3%,
      interquartile range: 4.3% to 9.2%). We identified various hospital patterns based
      on the type of agents: dobutamine-predominant (29% of hospitals), dopamine
      predominant (25%), milrinone-predominant (1%), mixed dobutamine and dopamine
      pattern (32%), and mixed pattern including all 3 agents (13%). When studying the
      factors associated with interhospital variation, the best model performance was
      with the hierarchical generalized linear models that adjusted for patient case
      mix and an individual hospital effect (receiver operating characteristic curves
      from 0.77 to 0.88). The intraclass correlation coefficients of the hierarchical
      generalized linear models (0.113 for any inotrope) indicated that a noteworthy
      proportion of the observed variation was related to an individual institutional
      effect. Hospital rates or patterns of use were not associated with differences in
      length of stay or risk-standardized mortality rates. CONCLUSIONS: We found marked
      differences in the use of inotropic agents for heart failure patients among a
      diverse group of hospitals. This variability, occurring in the context of little
      clinical evidence, indicates an urgent need to define the appropriate use of
      these medications.

PMID- 22981549
TI  - Tiara: a novel catheter-based mitral valve bioprosthesis: initial experiments and
      short-term pre-clinical results.

PMID- 22981550
TI  - Type 2 diabetes mellitus and risk of incident atrial fibrillation in women.
AB  - OBJECTIVES: The purpose of this study was to assess whether changes of major
      atrial fibrillation (AF) risk factors and/or intercurrent cardiovascular events
      could explain the relationship between type 2 diabetes mellitus (T2D) and
      incident AF. BACKGROUND: Previous studies found an increased risk of incident AF
      among individuals with T2D, but few, if any, of these studies took into account
      changes of AF risk factors over time. METHODS: A total of 34,720 female health
      professionals who participated in the Women's Health Study, and who were free of
      cardiovascular disease and AF at baseline were followed for a median of 16.4
      years. Cox proportional-hazards models were constructed to assess the
      relationship between T2D and incident AF, using either information at baseline or
      time-varying covariates for both T2D and potential confounders. RESULTS: At
      baseline, 937 (2.7 %) women had T2D. Compared with women without T2D, women with
      T2D had an age-adjusted hazard ratio (HR) for new-onset AF of 1.95 (95%
      confidence interval [CI]: 1.49 to 2.56; p<0.0001). In multivariable analyses
      adjusting for baseline confounders, this HR was substantially attenuated, but
      baseline T2D remained a significant predictor of incident AF (HR: 1.37, 95% CI:
      1.03 to 1.83; p=0.03). In time-updated models that adjusted for changes in AF
      risk factors and intercurrent cardiovascular events, the HR for T2D was
      attenuated further and became nonsignificant (HR: 1.14; 95% CI: 0.93 to 1.40;
      p=0.20). CONCLUSIONS: Although this study confirms a significant relationship
      between baseline T2D and incident AF, our data suggest that the increased risk
      associated with T2D is mainly mediated by changes of other AF risk factors.

PMID- 22981551
TI  - Post-dilation of superficial femoral artery stents with cryoplasty: does the
      COBRA Trial take a bite out of diabetic restenosis?

PMID- 22981552
TI  - Ivabradine: a ray of hope for inappropriate sinus tachycardia.

PMID- 22981553
TI  - Adolescence risk factors are predictive of coronary artery calcification at
      middle age: the cardiovascular risk in young Finns study.
AB  - OBJECTIVES: The purpose of this study was to examine the roles of adolescence
      risk factors in predicting coronary artery calcium (CAC). BACKGROUND: Elevated
      coronary heart disease risk factor levels in adolescence may predict subsequent
      CAC independently of change in risk factor levels from adolescence to adulthood.
      METHODS: CAC was assessed in 589 subjects 40 to 46 years of age from the
      Cardiovascular Risk in Young Finns Study. Risk factor levels were measured in
      1980 (12 to 18 years) and in 2007. RESULTS: The prevalence of any CAC was 19.2%
      (27.9% in men and 12.2% in women). Age, levels of systolic blood pressure (BP),
      total cholesterol, and low-density lipoprotein cholesterol (LDL-C) in
      adolescence, as well as systolic BP, total cholesterol, diastolic BP, and pack
      years of smoking in adulthood were higher among subjects with CAC than those
      without CAC. Adolescence LDL-C and systolic BP levels predicted CAC in adulthood
      independently of 27-year changes in these risk factors. The multivariable odds
      ratios were 1.34 (95% confidence interval: 1.05 to 1.70; p=0.02) and 1.38 (95%
      confidence interval: 1.08 to 1.77; p=0.01), for 1-SD increase in adolescence LDL
      C and systolic BP, respectively. Exposure to both of these risk factors in
      adolescence (defined as values at or above the age- and sex-specific 75th
      percentile) substantially increased the risk of CAC (multivariable odds ratio:
      3.5 [95% confidence interval: 1.7 to 7.2; p=0.007]) between groups with no versus
      both risk factors. CONCLUSIONS: Elevated adolescence LDL-C and systolic BP levels
      are independent predictors of adulthood CAC, indicating that adolescence risk
      factor levels play an important role in the pathogenesis of coronary heart
      disease.

PMID- 22981554
TI  - "The child is father of the man" (William Wordsworth, 1802).

PMID- 22981555
TI  - Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia:
      a prospective, randomized, placebo-controlled, double-blind, crossover
      evaluation.
AB  - OBJECTIVES: The purpose of this study was to investigate the role of ivabradine
      in the treatment of symptomatic inappropriate sinus tachycardia using a double
      blind, placebo-controlled, crossover design. BACKGROUND: Due to its I(f) blocking
      properties, ivabradine can selectively attenuate the high discharge rate from
      sinus node cells, causing inappropriate sinus tachycardia. METHODS: Twenty-one
      patients were randomized to receive placebo (n=10) or ivabradine 5 mg twice daily
      (n=11) for 6 weeks. After a washout period, patients crossed over for an
      additional 6 weeks. Each patient underwent symptom evaluation and heart rate
      assessment at the start and finish of each phase. RESULTS: After taking
      ivabradine, patients reported elimination of >70% of symptoms (relative risk:
      0.25; 95% CI: 0.18 to 0.34; p<0.001), with 47% of them experiencing complete
      elimination. These effects were associated with a significant reduction of heart
      rate at rest (from 88+/-11 beats/min to 76+/-11 beats/min, p=0.011), on standing
      (from 108+/-12 beats/min to 92+/-11 beats/min, p<0.0001), during 24 h (from 88+/
      5 beats/min to 77+/-9 beats/min, p=0.001), and during effort (from 176+/-17
      beats/min to 158+/-16 beats/min, p=0.001). Ivabradine administration was also
      associated with a significant increase in exercise performance. No cardiovascular
      side effects were observed in any patients while taking ivabradine. CONCLUSIONS:
      In this cohort, ivabradine significantly improved symptoms associated with
      inappropriate sinus tachycardia and completely eliminated them in approximately
      half of the patients. These findings suggest that ivabradine may be an important
      agent for improving symptoms in patients with inappropriate sinus tachycardia.

PMID- 22981556
TI  - Cardiac arrest in a long-distance ski race (Vasaloppet) in Sweden.

PMID- 22981557
TI  - Cardiac outcomes with submaximal normal stress echocardiography: a meta-analysis.
AB  - OBJECTIVES: The aim of the study was to evaluate the risk of cardiac events in
      patients with normal stress echocardiography (SE) who attained maximal age
      predicted heart rate (APHR) compared with those who did not in the setting of
      both normal and abnormal SE. BACKGROUND: SE is an important tool in the risk
      stratification and prognosis of patients with known or suspected coronary artery
      disease (CAD). The prognostic value of a normal but submaximal SE (<85% of
      maximal APHR) is conflicting. METHODS: PubMed, EMBASE, and CENTRAL were searched
      from 1980 to September 2011 for SE studies reporting cardiac outcomes in patients
      with known or suspected CAD stratified by achieved APHR. Both hard events
      (cardiac death and myocardial infarction) and total cardiac events
      (revascularization procedures in addition to hard events) were analyzed
      separately. Data on all-cause mortality were obtained when available. RESULTS:
      Fourteen studies with 11,542 patients followed up for a mean duration of 32
      months fulfilled the inclusion criteria. In 8 studies with 4,577 patients, the
      risk of hard events with normal SE (both exercise and dobutamine) was 70% higher
      in patients who achieved submaximal compared with those with maximal APHR
      (annualized event rate 2.08% vs. 0.77%; p=0.0008; 95% confidence interval [CI]:
      1.25 to 2.31). In 7 studies with 5,798 patients, the risk of total cardiac events
      with normal SE (both exercise and dobutamine) was 127% higher in patients who
      achieved submaximal compared with those with maximal APHR (annualized event rate
      1.87% vs. 1.02%; p<0.0001; 95% CI: 1.54 to 3.34). The risk of total cardiac
      events was 278% higher in patients with abnormal SE with submaximal APHR compared
      with those with normal SE with submaximal APHR (p<0.0001; 95% CI: 2.81 to 5.08).
      There was a trend toward increased all-cause mortality in patients with normal SE
      with submaximal compared with maximal APHR (relative risk: 1.36; p=0.15; 95% CI:
      0.89 to 2.09). CONCLUSIONS: Patients with submaximal APHR in the setting of
      normal SE have a higher risk of cardiovascular events than those who attained
      maximal stress test. Thus, the results of submaximal APHR in the setting of
      normal SE should be taken into consideration for more accurate risk
      stratification and prognosis.

PMID- 22981558
TI  - Pilot trial of cryoplasty or conventional balloon post-dilation of nitinol stents
      for revascularization of peripheral arterial segments: the COBRA trial.
AB  - OBJECTIVES: The purpose of this study is to compare post-dilation strategies of
      nitinol self-expanding stents implanted in the superficial femoral artery of
      diabetic patients with peripheral arterial disease. BACKGROUND: Endovascular
      treatment of superficial femoral artery disease with nitinol self-expanding
      stents is associated with high rates of in-stent restenosis in patients with
      diabetes mellitus. METHODS: We conducted a prospective, multicenter, randomized,
      controlled clinical trial of diabetic patients to investigate whether post
      dilation of superficial femoral artery nitinol self-expanding stents using a
      cryoplasty balloon reduces restenosis compared to a conventional balloon.
      Inclusion criteria included diabetes mellitus, symptomatic peripheral arterial
      disease, and superficial femoral artery lesions requiring implantation of
      stents>5 mm in diameter and >60 mm in length. Primary endpoint was binary
      restenosis at 12 months, defined as >=2.5-fold increase in peak systolic velocity
      by duplex ultrasonography. RESULTS: Seventy-four patients, with 90 stented
      superficial femoral artery lesions, were randomly assigned to post-dilation using
      cryoplasty (n=45 lesions) or conventional balloons (n=45 lesions). Mean lesion
      length was 148+/-98 mm, mean stented length was 190+/-116 mm, mean stent diameter
      was 6.1+/-0.4 mm, and 50% of the lesions were total occlusions. Post-dilation
      balloon diameters were 5.23+/-0.51 mm versus 5.51+/-0.72 mm in the cryoplasty and
      conventional balloon angioplasty groups, respectively (p=0.02). At 12 months,
      binary restenosis was significantly lower in the cryoplasty group (29.3% vs.
      55.8%, p=0.01; odds ratio: 0.36, 95% confidence interval: 0.15 to 0.89).
      CONCLUSIONS: Among diabetic patients undergoing implantation of nitinol self
      expanding stents in the superficial femoral artery, post-dilation with cryoplasty
      balloon reduced binary restenosis compared to conventional balloon angioplasty.
      (Study Comparing Two Methods of Expanding Stents Placed in Legs of Diabetics With
      Peripheral Vascular Disease [COBRA]; NCT00827853).

PMID- 22981559
TI  - Gender, health ambiguity, and depression among survivors of first stroke: a pilot
      study.
AB  - OBJECTIVE: To investigate the association between health ambiguity and depressive
      symptoms among stroke survivors and whether survivor gender moderates this
      association. DESIGN: Cross-sectional survey study. SETTING: General community.
      PARTICIPANTS: Survivors of first stroke (N=36) recruited through provider
      referral, support groups, and print and Web-based sources. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Depressive symptoms as measured by the Patient
      Health Questionnaire-9. RESULTS: Health ambiguity (beta=.984, P<.001), gender
      (beta=1.010, P<.01), and the interaction of the 2 variables (beta=-1.269, P<.05)
      were significantly associated with depressive symptoms. Simple slopes tests
      indicated that the association between health ambiguity and depressive symptoms
      was stronger for male versus female survivors. CONCLUSIONS: Gender and health
      ambiguity impact survivor depressive symptoms, independently and in conjunction
      with one another. Results are promising, and further research with larger samples
      and more comprehensive statistical models is needed to confirm these findings.

PMID- 22981560
TI  - Chemotherapy drug thioTEPA exacerbates stress-induced anhedonia and
      corticosteroid responses but not impairment of hippocampal cell proliferation in
      adult mice.
AB  - Cancer patients often suffer long-lasting affective and cognitive impairments as
      a result of chemotherapy treatment. Previous work in our lab has shown deficits
      in learning and memory and hippocampal cell proliferation in mice lasting up to
      20 weeks following acute administration of thioTEPA. In this study, the effects
      of thioTEPA in conjunction with effects of chronic stress on depression-related
      behavior were examined in C57BL/6J mice, 12 weeks following thioTEPA
      administration. Chemotherapy-treated mice showed a diminished sucralose
      preference compared to controls that was further exacerbated after 2 weeks of
      daily restraint stress. This intensifying effect was not observed in the Porsolt
      forced swim test. Moreover, stress-induced corticosteroid responses were
      exaggerated in thioTEPA-treated mice. Cell proliferation in the dentate gyrus of
      the hippocampus was also impaired similarly by prior thioTEPA treatment and by
      daily restraint stress, with no additive effect. Results suggest that some
      depression-related impairments may be exacerbated by chemotherapy treatment
      through altered corticosteroid regulation.

PMID- 22981561
TI  - Activity-based anorexia is associated with reduced hippocampal cell proliferation
      in adolescent female rats.
AB  - Activity-based anorexia (ABA) is an animal model of anorexia nervosa that mimics
      core features of the clinical psychiatric disorder, including severe food
      restriction, weight loss, and hyperactivity. The ABA model is currently being
      used to study starvation-induced changes in the brain. Here, we examined
      hippocampal cell proliferation in animals with ABA (or the appropriate control
      conditions). Adolescent female Sprague-Dawley rats were assigned to 4 groups:
      control (24h/day food access), food-restricted (1h/day food access), exercise
      (24h/day food and wheel access), and ABA (1h/day food access, 24h/day wheel
      access). After 3 days of ABA, 5-bromo-2'-deoxyuridine (BrdU; 200mg/kg, i.p.) was
      injected and the rats were perfused 2h later. Brains were removed and
      subsequently processed for BrdU and Ki67 immunohistochemistry. The acute
      induction of ABA reduced cell proliferation in the dentate gyrus. This effect was
      significant in the hilus region of the dentate gyrus, but not in the subgranular
      zone, where adult neurogenesis occurs. Marked decreases in cell proliferation
      were also observed in the surrounding dorsal hippocampus and in the corpus
      callosum. These results indicate a primary effect on gliogenesis rather than
      neurogenesis following 3 days of ABA. For each brain region studied (except SGZ),
      there was a strong positive correlation between the level of cell proliferation
      and body weight/food intake. Future studies should examine whether these changes
      are maintained following long-term weight restoration and whether alterations in
      neurogenesis occur following longer exposures to ABA.

PMID- 22981562
TI  - The neural correlates of affect reading: an fMRI study on faces and gestures.
AB  - As complex social beings, people communicate, in addition to spoken language,
      also via nonverbal behavior. In social face-to-face situations, people readily
      read the affect and intentions of others in their face expressions and gestures
      recognizing their meaning. Importantly, the addressee further has to discriminate
      the meanings of the seen communicative motor acts in order to be able to react
      upon them appropriately. In this functional magnetic resonance imaging study 15
      healthy non-alexithymic right-handers observed video-clips that showed the
      dynamic evolution of emotional face expressions and gestures evolving from a
      neutral to a fully developed expression. We aimed at disentangling the cerebral
      circuits related to the observation of the incomplete and the subsequent
      discrimination of the evolved bodily expressions of emotion which are typical for
      everyday social situations. We show that the inferior temporal gyrus and the
      inferior and dorsal medial frontal cortex in both cerebral hemispheres were
      activated early in recognizing faces and gestures, while their subsequent
      discrimination involved the right dorsolateral frontal cortex. Interregional
      correlations showed that the involved regions constituted a widespread circuit
      allowing for a formal analysis of the seen expressions, their empathic processing
      and the subjective interpretation of their contextual meanings. Right-left
      comparisons revealed a greater activation of the right dorsal medial frontal
      cortex and the inferior temporal gyrus which supports the notion of a right
      hemispheric dominance for processing affective body expressions. These novel data
      provide a neurobiological basis for the intuitive understanding of other people
      which is relevant for socially appropriate decisions and intact social
      functioning.

PMID- 22981563
TI  - Mismatch responses to lexical tone, initial consonant, and vowel in Mandarin
      speaking preschoolers.
AB  - The present study investigates how age, phonological saliency, and deviance size
      affect the presence of mismatch negativity (MMN) and positive mismatch response
      (P-MMR). This work measured the auditory mismatch responses to Mandarin lexical
      tones, initial consonants, and vowels in 4- to 6-year-old preschoolers using the
      multiple-deviant oddball paradigm. The data showed the coexistence of MMN and P
      MMR in the same age group when responding to the three types of syllabic features
      in Mandarin. The transition from a predominantly positive response to a
      predominantly negative response supported the multiple MMN mechanisms. Congruent
      with the phonological saliency hypothesis and the phonetic acquisition order of
      Mandarin in behavioral studies, for the compulsory elements of Mandarin
      syllables, lexical tones, and vowels, the larger deviants elicited adult-like
      MMNs, whereas the smaller deviants elicited P-MMRs. The optional elements of the
      Mandarin syllables, the initial consonant, only elicited P-MMR in preschoolers.
      These findings suggest that MMN and P-MMR index different functional
      characteristics and may provide information on when and how children's speech
      perception becomes automatic at different developmental stages.

PMID- 22981564
TI  - Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles
      and doxorubicin for combined gene therapy and chemotherapy.
AB  - We have designed and evaluated a dual anticancer delivery system to provide
      combined gene therapy and chemotherapy. Double-walled microspheres consisting of
      a poly(d,l-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(lactic acid)
      (PLA) shell were fabricated via the precision particle fabrication (PPF)
      technique. We make use of the advantages of double-walled microspheres to deliver
      chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor
      protein (chi-p53) and/or doxorubicin (Dox), loaded in the shell and core phases,
      respectively. Different molecular weights of PLA were used to form the shell
      layer for each formulation. The microspheres were monodisperse with a mean
      diameter of 65 to 75 MUm and uniform shell thickness of 8 to 17 MUm. Blank and
      Dox-loaded microspheres typically exhibited a smooth surface with relatively few
      small pores, while chi-microspheres containing p53 nanoparticles, with and
      without Dox, presented rough and porous surfaces. The encapsulation efficiency of
      Dox was significantly higher when it was encapsulated alone compared to co
      encapsulation with chi-p53 nanoparticles. The encapsulation efficiency of chi-p53
      nanoparticles, on the other hand, was not affected by the presence of Dox. As
      desired, chi-p53 nanoparticles were released first, followed by simultaneous
      release of chi-p53 nanoparticles and Dox at a near zero-order rate. Thus, we have
      demonstrated that the PPF method is capable of producing double-walled
      microspheres and encapsulating dual agents for combined modality treatment, such
      as gene therapy and chemotherapy.

PMID- 22981565
TI  - Amphiphilic HPMA-LMA copolymers increase the transport of Rhodamine 123 across a
      BBB model without harming its barrier integrity.
AB  - The successful non-invasive treatment of diseases associated with the central
      nervous system (CNS) is generally limited by poor brain permeability of various
      developed drugs. The blood-brain barrier (BBB) prevents the passage of
      therapeutics to their site of action. Polymeric drug delivery systems are
      promising solutions to effectively transport drugs into the brain. We recently
      showed that amphiphilic random copolymers based on the hydrophilic p(N-(2
      hydroxypropyl)-methacrylamide), pHPMA, possessing randomly distributed
      hydrophobic p(laurylmethacrylate), pLMA, are able to mediate delivery of
      domperidone into the brain of mice in vivo. To gain further insight into
      structure-property relations, a library of carefully designed polymers based on
      p(HPMA) and p(LMA) was synthesized and tested applying an in vitro BBB model
      which consisted of human brain microvascular endothelial cells (HBMEC). Our model
      drug Rhodamine 123 (Rh123) exhibits, like domperidone, a low brain permeability
      since both substances are recognized by efflux transporters at the BBB. Transport
      studies investigating the impact of the polymer architecture in relation to the
      content of hydrophobic LMA revealed that random p(HPMA)-co-p(LMA) having 10mol%
      LMA is the most auspicious system. The copolymer significantly increased the
      permeability of Rh123 across the HBMEC monolayer whereas transcytosis of the
      polymer was very low. Further investigations on the mechanism of transport showed
      that integrity and barrier function of the BBB model were not harmed by the
      polymer. According to our results, p(HPMA)-co-p(LMA) copolymers are a promising
      delivery system for neurological therapeutics and their application might open
      alternative treatment strategies.

PMID- 22981566
TI  - Effects of dietary betaine on milk yield and milk composition of mid-lactation
      Holstein dairy cows.
AB  - Betaine, naturally found in plants and an oxidative product of choline, is
      converted to acetate in the rumen, which may be used for milk fat synthesis. The
      objective of this study was to determine the effect of supplemental dietary
      betaine on milk yield and milk composition. Eighteen Holstein dairy cows (126+/-5
      d in milk; mean +/- SD) were randomly assigned to a sequence of treatments of
      rumen-unprotected betaine at 0, 25, 50, and 100 g/d added to a standard lactation
      ration in a 4*4 Latin square design. Animals were fed individually with feed
      intake and milk yield recorded daily. Body condition score and body weight were
      recorded on the last day of each period that lasted 16 d, with milk sampled on
      the last 2 d of each period. Milk composition was determined by a Dairy Herd
      Improvement Association laboratory and milk fatty acids were determined by gas
      chromatography. Data collected over the last 2 to 3 d were analyzed using the
      MIXED procedure in SAS (SAS Institute Inc., Cary, NC). Milk yield (mean +/- SEM)
      was increased by betaine when fed at 100g/d (22.4, 22.5, 22.8, 24.1+/-1.19 kg/d
      for 0, 25, 50, and 100g of betaine/d, respectively). No effect of dietary betaine
      was detected on dry matter intake, feed efficiency, body weight, or body
      condition score. Percentages of milk fat, lactose, solids-not-fat, and somatic
      cell count were not altered; however, protein concentration was decreased by
      betaine supplementation as compared with the control (3.35, 3.28, 3.27, and
      3.28+/-0.07% for 0, 25, 50, and 100 g of betaine/d, respectively). Daily yields
      of milk protein, fat, lactose, energy-corrected milk, and 3.5% fat-corrected milk
      did not differ with betaine supplementation. Overall, inclusion of dietary
      betaine at 100 g/d increased milk yield, whereas all levels of betaine
      supplementation decreased milk protein percent and slightly altered milk fatty
      acid profile. Further studies are needed to determine the ruminal fermentation
      characteristics and the optimum rate of supplemental betaine for dairy cows.

PMID- 22981567
TI  - Survival of microencapsulated probiotic Lactobacillus paracasei LBC-1e during
      manufacture of Mozzarella cheese and simulated gastric digestion.
AB  - An erythromycin-resistant strain of probiotic Lactobacillus paracasei ssp.
      paracasei LBC-1 (LBC-1e) was added to part-skim Mozzarella cheese in alginate
      microencapsulated or free form at a level of 10(8) and 10(7)cfu/g, respectively.
      Survival of LBC-1e and total lactic acid bacteria (LAB) was investigated through
      the pasta filata process of cheese making (in which the cheese curd was heated to
      55  degrees C and stretched in 70  degrees C-hot brine), followed by storage at 4
      degrees C for 6 wk and simulated gastric and intestinal digestion. This included
      incubation in 0.1 M and 0.01 M HCl, 0.9 M H(3)PO(4), and a simulated intestinal
      juice consisting of pancreatin and bile salts in a pH 7.4 phosphate buffer. Some
      reductions were observed in both free and encapsulated LBC-1e during heating and
      stretching, with encapsulated LBC-1e surviving slightly better. Changes in total
      LAB losses during heating and stretching did not reach statistical significance.
      During storage, a decrease was observed in total LAB, but no statistically
      significant decrease was observed in LBC-1e. Survival during gastric digestion in
      HCl was dependent on the extent of neutralization of HCl by the cheese, with more
      survival in the weaker acid, in which pH increased to 4.4 after cheese addition.
      The alginate microcapsules did not provide any protection against the HCl. It is
      interesting that survival of the encapsulated LBC-1e was greater during
      incubation in H(3)PO(4) than in the HCl gastric juices. Proper selection of
      simulated gastric digestion media is important for predicting the delivery of
      probiotic bacteria into the human intestinal tract. Neither free nor encapsulated
      LBC-1e was affected by incubation in the pancreatin-bile solution. Based on the
      level of probiotic bacteria in cheese needed to provide a health benefit and its
      survival during simulated gastric digestion, as determined in this study, it
      should theoretically be possible to lower the amount that needs to be ingested in
      cheese by up to a factor of 10(3) compared with other fermented dairy foods or
      when consumed as supplements.

PMID- 22981568
TI  - Hot topic: association of telomere length with age, herd, and culling in
      lactating Holsteins.
AB  - Telomere length variation may provide a quantitative measure of the effects of
      dairy management and selection practices on animal stress and welfare. The
      objective of this study was to evaluate the association between telomere length
      in Holstein cattle with age, herd, and survival. A multiplex quantitative PCR
      (qPCR) procedure was utilized to estimate telomere length for 201 Holstein cows
      from 10 herds following DNA extraction from blood. Primers were designed to
      amplify a 79-bp telomere product and a 144-bp product of a standard reference
      gene (beta-globin). Both primer sets were included in the same reaction well to
      enable the analysis of relative quantity (qT) of telomere product compared with
      beta-globin product. Triplicate samples were run for each cow, and mixed models
      were used to analyze the qPCR results. Younger cows were significantly associated
      with higher qT, and significant variation was observed among herds for qT. Cows
      with short telomeres were more likely to be culled in the subsequent year than
      cows with above-average telomere lengths. Multiplex qPCR provides a cost
      effective method of assessing telomere length. Variation in telomere length might
      provide insights into how management practices and genetic selection influence
      cow stress and physiological responses to stress.

PMID- 22981569
TI  - Relationship between body condition score and health traits in first-lactation
      Canadian Holsteins.
AB  - The objective of this research was to estimate daily genetic correlations between
      longitudinal body condition score (BCS) and health traits by using a random
      regression animal model in first-lactation Holsteins. The use of indicator traits
      may increase the rate of genetic progress for functional traits relative to
      direct selection for functional traits. Indicator traits of interest are those
      that are easier to record, can be measured early in life, and are strongly
      genetically correlated with the functional trait of interest. Several BCS records
      were available per cow, and only 1 record per health trait (1=affected; 0=not
      affected) was permitted per cow over the lactation. Two bivariate analyses were
      performed, the first between BCS and mastitis and the second between BCS and
      metabolic disease (displaced abomasum, milk fever, and ketosis). For the first
      analysis, 217 complete herds were analyzed, which included 28,394 BCS records for
      10,715 cows and 6,816 mastitis records for 6,816 cows. For the second analysis,
      350 complete herds were analyzed, which included 42,167 BCS records for 16,534
      cows and 13,455 metabolic disease records for 13,455 cows. Estimation of variance
      components by a Bayesian approach via Gibbs sampling was performed using 400,000
      samples after a burn-in of 150,000 samples. The average daily heritability
      (posterior standard deviation) of BCS was 0.260 (0.026) and the heritabilities of
      mastitis and metabolic disease were 0.020 (0.007) and 0.041 (0.012),
      respectively. Heritability estimates were similar to literature values. The
      average daily genetic correlation between BCS and mastitis was -0.730 (0.110).
      Cows with a low BCS during the lactation are more susceptible to mastitis, and
      mastitic cows are likely to have low BCS. Daily estimates of genetic correlations
      between BCS and mastitis were moderate to strong throughout the lactation,
      becoming stronger as the lactation progressed. The average daily genetic
      correlation between BCS and metabolic disease was -0.438 (0.125), and was
      consistent throughout the lactation. A lower BCS during the lactation is
      genetically associated with the occurrence of mastitis and metabolic disease.

PMID- 22981570
TI  - Composite beta-kappa-casein genotypes and their effect on composition and
      coagulation of milk from Estonian Holstein cows.
AB  - The objective of this study was to estimate the effect of composite beta-kappa-CN
      genotypes on milk coagulation and composition traits, and on the additive genetic
      variation of these traits in Estonian Holstein dairy cattle. A total of 23,970
      milk samples, repeated measurements from the first to third lactation from 2,859
      Estonian Holstein cows from 78 herds across the country, were analyzed for milk
      yield, milk fat and protein percentages, somatic cell count, and milk coagulation
      properties (milk coagulation time and curd firmness). Each cow had at least 3
      measurements per lactation. Two single-trait random regression animal models were
      fitted for the traits studied. The first model considered fixed effects of year
      season of sampling and year-season of calving, calving age (nested within
      lactation), sample age (only for milk coagulation traits) and days in milk, and
      random herd, additive genetic, and permanent environmental effects. The animal
      and permanent environmental effects were modeled over the lactation period by
      using Legendre polynomials. The second model had the additional fixed beta-kappa
      casein effect in the form of a third-order Legendre polynomial. The 2 most
      frequent beta-kappa-casein composite genotypes were A2A2AA and A1A2AA, both with
      prevalence greater than 20%. Percentages of the remaining 31 genotypes were less
      than 8%, including 20 genotypes with percentages less than 1%. The beta-kappa
      casein genotype-specific lactation curves were significantly different for milk
      coagulation traits and milk protein percentage. The B variant of kappa-casein
      showed a favorable effect on both milk coagulation traits, whereas the IB
      haplotype had an increasing effect on curd firmness and protein percentage.
      Inclusion of the beta-kappa-casein genotype effects in the model resulted in
      decreases in the mean additive genetic variations for milk coagulation time and
      curd firmness of 12.9 and 51.1%, respectively.

PMID- 22981571
TI  - Usefulness of a large field of view sensor for physicochemical, textural, and
      yield predictions under industrial goat cheese (Murcia al Vino) manufacturing
      conditions.
AB  - The applicability of a light backscatter sensor with a large field of view was
      tested for on-line monitoring of coagulation and syneresis in a goat cheese
      (Murcia al Vino) manufactured under industrial conditions. Cheesemaking was
      carried out concurrently in a 12-L pilot vat and a 10,000-L industrial vat
      following the normal cheesemaking protocol. Cheese moisture, whey fat content,
      hardness, springiness, and adhesiveness were measured during syneresis. The
      results obtained show that cutting time is best predicted by considering the
      coagulation ratio at the inflection point and the percentage increase in the
      ratio during coagulation, with no need for the first derivative. The large field
      of view reflectance ratio provided good results for the prediction of moisture
      content, yield, hardness, springiness, and adhesiveness of the final cheese.

PMID- 22981573
TI  - Effect of exogenous protease enzymes on the fermentation and nutritive value of
      corn silage.
AB  - The objective of this study was to evaluate the effects of adding experimental
      formulations of exogenous protease enzymes on the fermentation and nutritive
      value of whole-plant corn ensiled in laboratory silos. Chopped and processed
      whole-plant corn (36.8% DM) was ensiled without enzymes or treated with 1 of 2
      experimental proteases (E85 or E86; AB Vista, Wiltshire, UK) at 20 or 2,000 mg/kg
      (wet-weight basis). Forages were packed in vacuumed and heat-sealed bags and
      ensiled for 45 and 150 d at 23+/-1 degrees C. When compared with untreated
      silage, addition of proteases and length of ensiling time had no effect on silage
      pH or concentration of crude protein. The results were similar for the
      concentrations of acid detergent fiber, neutral detergent fiber, and starch,
      although protease * time interactions were observed for these components, which
      were biologically minor. When compared with untreated silages, only treatment
      with the 2,000-mg/kg application amount of E 0425 resulted in lower neutral
      detergent fiber after 45 d of ensiling. Proteases did not affect NDF
      digestibility after 150 d of ensiling when compared with untreated silage.
      Similarly, treatment with enzymes did not affect the concentrations of lactic and
      acetic acids or ethanol when compared with untreated silage. Concentrations of
      NH(3)-N and soluble protein (% of crude protein) increased with storage time
      compared with concentrations at harvest and were greater for the 2,000-mg/kg
      doses of proteases when compared with untreated silage at both 45 and 150 d. In
      vitro ruminal digestibility of starch after 7 h of incubation was 66.3% for
      freshly chopped corn plants. After 45 d of ensiling, starch digestion was greater
      for E 0430 applied at the 2,000-mg/kg dose (80.6%) than in all other treatments,
      with the exception that it was similar to the 2,000-mg/kg dose of E85. After 150
      d of ensiling, the 20-mg/kg dose of E 0425 (81.9%), the 2,000-mg/kg dose of E
      0425 (82.9%), and the 2,000-mg/kg dose of E 0430 (88.6%) had greater starch
      digestibility than untreated silage (74.0%). To the best of our knowledge, this
      is the first study to show that addition of exogenous proteases added to corn
      forage at the time of harvest can increase in vitro ruminal starch digestibility
      during silage fermentation. Data suggests that adding exogenous sources of
      protease enzymes at ensiling may be a method to obtain a high degree of ruminal
      starch digestibility in corn silage that would normally require longer periods of
      time to obtain from prolonged storage.

PMID- 22981572
TI  - Oxidative stability of an extended shelf-life dairy-based beverage system
      designed to contribute to heart health.
AB  - Skim milk, butter-derived aqueous phase, butter oil, and fish oil (3 levels) were
      used to produce UHT pasteurized n-3 fatty acid-fortified beverages (3.1% fat,
      3.9% protein, and 11.5% total solids) with targeted deliveries of 200, 500, and
      800 mg of eicosapentaenoic acid and docosahexaenoic acid (combined total) per 250
      mL (8 fl oz) serving. Microbial quality, emulsion stability, and oxidation of
      lipids over 35 d of storage at 4  degrees C were evaluated. Conjugated diene
      hydroperoxides were below 1% throughout storage and were found at highest
      concentrations around d 21 of storage for all formulations. Volatile analysis
      indicated an increase in 1-penten-3-ol in the n-3 fortified dairy-based beverage
      systems during storage. Triangle tests were conducted to determine if consumers
      could detect a difference in aroma, compared with commercially processed
      aseptically packaged milk. The beverage system with targeted delivery of 500 mg
      of eicosapentaenoic acid + docosahexaenoic acid per 250-mL serving was not
      different in aroma compared with commercially available UHT processed milk. This
      formulation delivered 432 mg of heart-healthy n-3 fatty acids per 250-mL serving
      on d 35 and was microbiologically and physically stable throughout the 35-d
      refrigerated storage period.

PMID- 22981574
TI  - Technical note: validating a dynamometer for noninvasive measuring of udder
      firmness in dairy cows.
AB  - Most measurements of udder pressure are based on devices connected to the gland
      cistern via cannulas. These devices are either inserted in the teat canal or
      surgically implanted into the udder tissue. In this study, instead of invasively
      measuring intramammary udder pressure, we measured the udder firmness
      noninvasively on the udder surface via a dynamometer. These are commonly used in
      food research to determine crispiness and firmness of fruits. The objective of
      this study was to validate a hand-held dynamometer for measuring udder firmness
      in dairy cows. Specifically we set out to determine inter-investigator
      repeatability considering potential confounders such as investigator, location,
      and cow. Through modifications in the standard operating procedure for the
      measurements, inter-investigator repeatability increased from correlation
      coefficient=0.80 (n=275) to correlation coefficient=0.94 (n=634). Measurements in
      different locations within the left hind quarter revealed a firmness gradient
      from the upper to the lower measuring point. Measurements between the 4 quarters
      within a cow displayed differences, except between both hind quarters. In 94.8%
      of the udders, firmness decreased due to milking. The correlation coefficient,
      however, between firmness changes and milk yield was low (r=0.42, n=153). Our
      data provide evidence that the dynamometer, although imperfect, does provide a
      reasonable measure of udder firmness and can be a useful tool in research related
      to animal health and welfare. However, a standardized operating protocol should
      be followed to minimize confounding by investigator, location, and quarter.

PMID- 22981575
TI  - Effect of the high-pressure-release phase on the protein composition of the
      soluble milk fraction.
AB  - This paper describes a study on the influence of the high-pressure-release rate
      on the protein distribution between the soluble and colloidal fractions of milk.
      Skim milk, without or with sulfhydryl-blocking agents, was pressure treated at
      250 and 350 MPa for 5 to 15 min at 25  degrees C, applying different pressure
      release rates (pressure-release times between 0.07 to 10 min). The liberation of
      caseins to the soluble phase and the denaturation of whey proteins were assessed.
      A significantly higher increase in the content of soluble casein took place
      during the pressure-release phase as compared with a pressure-holding phase.
      Denaturation of beta-lactoglobulin mainly took place by -SH-S-S exchange
      reactions during the holding phase. The present results, thus, show a negligible
      influence of whey proteins on the increase in the content of nonsedimentable
      casein in pressure-treated milk and provide evidence for the importance of the
      pressure-release rate in this process, so that the slower the pressure release
      rate, the higher the level of soluble casein.

PMID- 22981576
TI  - Effect of abomasal emptying rate on the apparent efficiency of colostral
      immunoglobulin G absorption in neonatal Holstein-Friesian calves.
AB  - Inadequate absorption of colostral IgG in calves increases the risk of morbidity
      and death and is an important source of economic loss to the dairy industry. We
      hypothesized that an increased rate of abomasal emptying in colostrum-fed calves
      would be associated with an increased apparent efficiency of absorption (AEA) of
      colostral IgG. This is because an increase in abomasal emptying rate causes IgG
      to reach the site of absorption in the small intestine earlier and at a higher
      luminal concentration. The main objective was, therefore, to determine the
      association between the AEA of colostral IgG and abomasal emptying rate in
      neonatal calves. Twenty-four neonatal Holstein-Friesian calves were randomly
      assigned to one of the following treatments: control, 2 mL of 0.9% NaCl
      intramuscularly; erythromycin, 8.8 mg/kg of body weight intramuscularly;
      ivermectin, 200 MUg/kg intravenously; and gentamicin, 6.6 mg/kg intramuscularly.
      These treatments were selected because we have previously demonstrated that
      erythromycin and ivermectin increase, and gentamicin decreases, the rate of
      abomasal emptying in milk-fed calves. Calves were fed 3 L of pooled cow colostrum
      containing acetaminophen (50mg/kg of body weight) by oroesophageal intubation at
      1h of age and 30 min after each treatment was administered. Jugular venous blood
      samples were obtained periodically after the start of feeding. Abomasal emptying
      rate was assessed by the time to maximal plasma acetaminophen concentration.
      Erythromycin increased and gentamicin decreased the abomasal emptying rate and
      AEA of colostral IgG compared with control, respectively, whereas ivermectin had
      no effect. Using data from all 24 calves, the AEA of colostral IgG was linearly
      and negatively associated with abomasal emptying rate (R(2)=0.22). We conclude
      that the abomasal emptying rate is an important determinant of the AEA of
      colostral IgG. Identifying a non-antimicrobial method for increasing abomasal
      emptying rate will provide a practical and effective method for facilitating
      transfer of passive immunity in colostrum-fed dairy calves.

PMID- 22981577
TI  - Factors determining milk quality and implications for production structure under
      somatic cell count standard modification.
AB  - Consumer and processor demand for high-quality milk has placed increasing
      pressure on US milk producers to achieve higher product standards. International
      standards for somatic cell count (SCC) are becoming more stringent, but in May
      2011, the United States National Conference on Interstate Milk Shipments chose to
      retain the 750,000 cells/mL standard. Using ordinary least squares and quantile
      regressions on US Department of Agriculture Agricultural Resource Management
      Survey Dairy Costs and Returns Report data for 2005, we model producer and farm
      level characteristics associated with SCC. Quantile regression analysis allows
      for a more parsed inquiry into statistical associations. Dairy Costs and Returns
      Report data provide cross-sectional information on the physical structure, input
      expenses, demographics, and outputs for farms in selected states. Location
      outside the Southeast, lower herd age, full-time farming status, use of
      biosecurity guidelines, good milking facilities and operations management, and
      application of related quality tests are all associated with lower SCC levels.
      Size of operation had little effect on SCC levels after controlling for other
      factors. Many of the operations that did not attain a more demanding SCC standard
      of 400,000 cells/mL had older operators, operators who expressed intention to
      exit within 10 yr, smaller size, and location in the Southeast when compared with
      those meeting the tighter standard. The results suggest that the stricter scheme
      favors larger farms that are more committed to production and are less likely to
      be sole or family proprietorships.

PMID- 22981578
TI  - Commensal symbiosis between a Lactococcus lactis strain and an Enterococcus
      mundtii strain increases cell yield in constituted broth.
AB  - To exert their beneficial effects, probiotics need to survive in the stringent
      conditions of the gastrointestinal tract. Symbiosis between different bacteria is
      a potential way of enhancing this survival. In developing new probiotic cultures,
      we investigated the synergic effect between Enterococcus mundtii IFO 13712 and 7
      strains of Lactococcus lactis, many of which are widely used as starter bacteria
      for making dairy products and have probiotic properties. The growth yield of a
      mixed culture of L. lactis strain Y and IFO 13712 in de Man, Rogosa, and Sharpe
      broth was greater than that of a single culture. Supernatant from culture of
      strain IFO 13712 enhanced the growth of strain Y, but that of strain Y did not
      enhance the growth of strain IFO 13712. This commensalism phenomenon was
      confirmed by using a simpler tryptone-yeast extract-glucose (TYG) broth.
      Increased cell yield in mixed culture of the 2 strains compared with single
      cultures was observed in TYG broth in the presence of both Tween 80 and citrate
      but not in TYG broth alone or TYG broth containing either Tween 80 or citrate.
      Thus, the Tween 80 and citrate in the broth contributed to the commensalism.
      Metabolite analysis revealed that ethanol production in the co-metabolism of
      glucose and citrate by strain Y was suppressed by mixed culture in TYG broth
      containing Tween 80 and citrate, compared with that in TYG broth containing
      citrate alone. The mechanism supporting the observed commensal symbiosis between
      strains Y and IFO 13712 was the increase in availability of glucose for lactate
      production by strain Y because, in glycolysis, the pathway from glucose to
      lactate is energic, whereas the pathway from glucose to ethanol is not. Whether
      growth stimulation of strain Y by mixing it with IFO 13712 in milk products will
      enhance the survival of strain Y in the intestine remains to be elucidated.

PMID- 22981579
TI  - Bayesian estimation of the diagnostic accuracy of a multiplex real-time PCR assay
      and bacteriological culture for 4 common bovine intramammary pathogens.
AB  - Bacteriological culture (BC) is the traditional method for intramammary infection
      diagnosis but lacks sensitivity and is time consuming. Multiplex real-time PCR
      (mr-PCR) enables testing the presence of several bacteria and reduces diagnosis
      time. Our objective was to estimate bacterial species-specific sensitivity (Se)
      and specificity of both BC and mr-PCR tests for detecting bacteria in milk
      samples from clinical mastitis cases and from apparently normal quarters, using a
      Bayesian latent class model. Milk samples from 1,014 clinical mastitis cases and
      1,495 samples from apparently normal quarters were analyzed by BC and mr-PCR. Two
      positive culture definitions were used: >=1 cfu/0.01 mL and >=10 cfu/0.01 mL of
      the specified bacteria. The mr-PCR was designed to simultaneously detect
      Staphylococcus aureus, Streptococcus uberis, Escherichia coli, and Streptococcus
      agalactiae. The priors used in our Bayesian model were weakly informative, with
      BC priors using the best available error data. Results were compared with those
      obtained using uniform priors for mr-PCR to test robustness. Weak and uniform
      priors gave about the same posterior distributions except for Strep. uberis from
      normal quarters and Strep. agalactiae. Multiplex real-time PCR Se on milk from
      clinical mastitis were lower than mr-PCR Se on milk from normal quarters.
      Multiplex real-time PCR Se was higher than BC on milk from normal quarters.
      Multiplex real-time PCR Se was generally lower than BC on milk from clinical
      mastitis and it varied by clinical severity. The estimate specificities of
      detection for all pathogens were >=99%, regardless of sample type. The effect of
      milk sample preservation before testing was evaluated and may have been a factor
      that affected our observed results. A significant association was observed
      between sample age and mr-PCR results leading to reduced detection of E. coli and
      Strep. agalactiae in nonclinical samples. Differences in sample age between
      conduct of BC and of mr-PCR did not concur with any apparent differences between
      Se estimates of the 2 tests. Further work should be done to extend these results
      to other PCR-based tests for detecting bacterial species in milk samples, for
      which presented results could be used as prior parameter distributions. Limits of
      sample handling and storage and the potential existence of substances in clinical
      case samples that may interfere with PCR reactions also are worth further
      investigation.

PMID- 22981580
TI  - Bovine milk fat globule membrane affects virulence expression in Escherichia coli
      O157:H7.
AB  - The aim of this study was to examine the effect of the bovine milk fat globule
      membrane (MFGM) on the virulence of Escherichia coli O157:H7. The MFGM was
      extracted from raw or heat-treated milk, resulting in 2 preparations differing in
      protein composition. Both heated and raw MFGM exerted an inhibitory effect on
      Shiga toxin gene expression by E. coli O157:H7 (ratios of -7.69 and -5.96,
      respectively). Interestingly, the effect was stronger with heated MFGM, with a
      larger decrease in expression of the virulence gene fliC (ratio of -9.43). The
      difference in effect observed between heated and raw MFGM could be explained by
      the difference in protein composition between the 2 preparations. These results
      show, for the first time, a specific effect of MFGM on expressionof Shiga toxin
      genes as well as genes involved in the motility of E. coli O157:H7. This may
      offer a new approach to mitigate the adverse health effects caused by E. coli
      O157:H7 infections.

PMID- 22981581
TI  - The effect of incomplete milking or nursing on milk production, blood
      metabolites, and immune functions of dairy cows.
AB  - During the transition from pregnancy to lactation, the sudden increase in
      nutrient demand for milk production causes metabolic perturbations and is
      associated with immunosuppression and a high incidence of metabolic and
      infectious diseases in high-yielding cows. In this study, we examined whether
      limiting milk harvest postpartum while maintaining milking stimulus could improve
      the metabolic status of cows without reducing overall milk production. Forty
      seven Holstein cows were milked completely twice a day from calving (control);
      milked incompletely (about one-third of expected milk production was collected)
      twice a day until d 5 after calving (incomplete); or left to nurse their calf
      until d 5 and milked once a day from d 3 to d 5 (nursing). All cows were milked
      twice a day from d 6 to the end of the experiment (d 61). During the treatment
      period (d 1 to 5), milk production averaged 27.3 and 9.7 kg/d for the control and
      incomplete treatments, respectively. We observed no residual effect of treatment
      on milk production, which averaged 47.8, 45.7, and 46.4 kg/d for the control,
      incomplete, and nursing treatments, respectively, between wk 2 and 9. The dry
      matter intake of the cows was similar during and after treatment. From wk 2 to 9,
      milk protein and lactose percentage were not affected by treatments, but milk fat
      tended to be higher in control cows than in cows milked partially (incomplete +
      nursing). Blood concentrations of glucose and phosphorus were lower and
      concentrations of nonesterified fatty acids and beta-hydroxybutyrate were higher
      in control cows than in partially milked cows during the treatment period. The
      positive effects on glucose and beta-hydroxybutyrate remained significant up to d
      28. Peripheral blood mononuclear cell (PBMC) proliferation and secretion of IL-4
      were depressed during the postpartum period, and proliferation tended to be
      greater for cells incubated in serum from cows in the incomplete treatment on d 5
      but lower on d 61. We observed no effect of treatments on polymorphonuclear
      neutrophilic leukocyte chemotaxis or phagocytosis. Proliferation and IL-4
      secretion of PBMC were negatively correlated with concentration of serum
      nonesterified fatty acids. Reducing milk harvest postpartum while maintaining
      milking stimuli reduced metabolic stress without compromising productivity of
      high-yielding dairy cows.

PMID- 22981582
TI  - Examining the effect of intramammary infections with minor mastitis pathogens on
      the acquisition of new intramammary infections with major mastitis pathogens--a
      systematic review and meta-analysis.
AB  - Major mastitis pathogens such as Staphylococcus aureus, Streptococcus agalactiae,
      Streptococcus uberis, Streptococcus dysgalactiae, and the coliforms are usually
      considered more virulent and damaging to the udder than minor mastitis pathogens
      such as Corynebacterium bovis and coagulase-negative staphylococci (CNS). The
      current literature contains several studies detailing analyses with conflicting
      results as to whether intramammary infection (IMI) with the minor pathogens
      decreases, increases, or has no effect on the risk of a quarter acquiring a new
      intramammary infection (NIMI) with a major pathogen. To investigate the available
      scientific evidence regarding the effect of IMI with minor pathogens on the
      acquisition of NIMI with major pathogens, a systematic review and meta-analysis
      were conducted. The total extant English- and French-language literature in
      electronic databases was searched and all publications cited by relevant papers
      were investigated. Results from 68 studies were extracted from 38 relevant
      papers. Random-effects models were used to investigate the effects of CNS and C.
      bovis on acquisition of new IMI with any of the major pathogens, as well as
      individually for the minor pathogens and Staph. aureus. Significant heterogeneity
      among studies exists, some of which could be accounted for by using meta
      regression. Overall, observational studies showed no effect, whereas challenge
      studies showed strong and significant protective effects, specifically when major
      pathogens were introduced into the mammary gland via methods bypassing the teat
      end. Underlying risk can account for several unmeasured factors, and studies with
      higher underlying risk found more protective effects of minor pathogens. Larger
      doses of challenge organisms reduced the protective effect of minor pathogens,
      and studies with more stringent diagnostic criteria for pathogen IMI identified
      less protection. Smaller studies (those utilizing fewer than 40 cows) also showed
      a greater protective effect than larger studies.

PMID- 22981583
TI  - Invited review: anaerobic fermentation of dairy food wastewater.
AB  - Dairy food wastewater disposal represents a major environmental problem. This
      review discusses microorganisms associated with anaerobic digestion of dairy food
      wastewater, biochemistry of the process, factors affecting anaerobic digestion,
      and efforts to develop defined cultures. Anaerobic digestion of dairy food
      wastewater offers many advantages over other treatments in that a high level of
      waste stabilization is achieved with much lower levels of sludge. In addition,
      the process produces readily usable methane with low nutrient requirements and no
      oxygen. Anaerobic digestion is a series of complex reactions that broadly involve
      2 groups of anaerobic or facultative anaerobic microorganisms: acidogens and
      methanogens. The first group of microorganisms breaks down organic compounds into
      CO(2) and volatile fatty acids. Some of these organisms are acetogenic, which
      convert long-chain fatty acids to acetate, CO(2), and hydrogen. Methanogens
      convert the acidogens' products to methane. The imbalance among the different
      microbial groups can lead not only to less methane production, but also to
      process failure. This is due to accumulation of intermediate compounds, such as
      volatile fatty acids, that inhibit methanogens. The criteria used for evaluation
      of the anaerobic digestion include levels of hydrogen and volatile fatty acids,
      methane:carbon ratio, and the gas production rate. A steady state is achieved in
      an anaerobic digester when the pH, chemical oxygen demand of the effluent, the
      suspended solids of the effluent, and the daily gas production remain constant.
      Factors affecting efficiency and stability of the process are types of
      microorganisms, feed C:N ratio, hydraulic retention time, reactor design,
      temperature, pH control, hydrogen pressure, and additives such as manure and
      surfactants. As anaerobic digesters become increasingly used in dairy plants,
      more research should be directed toward selecting the best cultures that maximize
      methane production from dairy food waste.

PMID- 22981584
TI  - Producer survey of bird-livestock interactions in commercial dairies.
AB  - The objective of this producer survey was to identify and estimate damage caused
      by bird-livestock interactions in commercial dairies. The interactions between
      birds and livestock have previously been implicated in causing economic damage
      while contributing to the environmental dissemination of microorganisms
      pathogenic to livestock and humans. Very little research exists to help producers
      understand what bird species use dairies, why they use dairies, or the scope and
      nature of damage created as a result of bird-livestock interactions. To better
      characterize these interactions, we surveyed dairy operators within Pennsylvania,
      New York, and Wisconsin. Survey results suggest that the most common and
      destructive bird species found on commercial dairies are invasive to North
      America, and their use of dairies is associated with the loss of cattle feed,
      increased operating costs, and an increase in dairies self-reporting Salmonella
      spp. and Mycobacterium avium ssp. paratuberculosis. Cattle feed loss estimates
      generated from this survey were used to parameterize an input-output (IO)
      economic model using data from 10 counties in the state of Pennsylvania (Bedford,
      Berks, Blair, Bradford, Chester, Cumberland, Franklin, Lancaster, Lebanon, and
      Somerset). This IO model allowed us to estimate direct, indirect, and induced
      economic effects of feed loss from bird damage to dairies within these counties.
      The IO model output suggests that feed loss costs Pennsylvania between $4.11 and
      $12.08 million (mean $10.6 million) in total economic damage, with approximately
      43 to 128 jobs (mean 112) forgone statewide in 2009.

PMID- 22981585
TI  - Individual animal variability in ruminal bacterial communities and ruminal
      acidosis in primiparous Holstein cows during the periparturient period.
AB  - The purpose of this study was to investigate variability among individual cows in
      their severity of ruminal acidosis (RA) pre- and postpartum, and determine
      whether this variability was related to differences in their ruminal bacterial
      community composition (BCC). Variability in the severity of RA among individual
      cows was characterized based on ruminal fermentation variables. Effects of
      prepartum dietary treatment on the severity of RA were also examined. Fourteen
      Holstein heifers paired by expected calving date and BCS were allotted to 1 of 2
      prepartum dietary treatments: low-concentrate or high-concentrate diets. All cows
      received the same lactation diet postpartum. Microbial DNA extracted from 58
      ruminal digesta samples in total collected prepartum (d -50, -31, and -14; 27
      samples) and postpartum (d +14 and +52; 31 samples) and amplified by PCR were
      subjected to automated ribosomal intergenic spacer analysis. Changes in ruminal
      variables over time [pH, volatile fatty acids (VFA), and acidosis indicators,
      including duration and area under the rumen pH curve below 5.8, 5.5, and 5.2,
      measured on d -54, -35, -14, -3, +3, +17, +37, and +58] were analyzed using
      principal components analysis. Based on the shift (defined as the distance of the
      mean loadings) between the prepartum and postpartum period for each cow, the 14
      cows were classified into 3 groups: least acidotic (n=5), most acidotic (n=5),
      and intermediate (n=4). Cows in the most acidotic group had greater severity of
      RA (measured as duration of total RA, mild RA, moderate RA, and acute RA; area
      under the pH curve for total RA, mild RA, and moderate RA) postpartum than
      prepartum, and this difference between periods was greater than for the least
      acidotic cows. Similarly, the RA index (total area of pH <5.8 normalized to
      intake) showed an interaction between severity of RA and period. The variation in
      the severity of RA was independent of intake, total VFA concentration, and
      individual VFA proportions. Production variables (milk yield, fat percentage, fat
      yield, fat-corrected milk, and efficiency of milk production) were not influenced
      by the severity of RA. Ruminal BCC was not influenced by dietary treatment or
      period. However, some cows experienced greater shift in BCC than other cows
      across the periods. Based on the magnitude of the shift in BCC (distance between
      mean ordination values across the periods for each cow), cows were grouped into 3
      BCC profile categories: stable (5 cows with lesser shift), unstable (5 cows with
      greater shift), and intermediate (4 cows with average shift). Cows demonstrating
      a greater shift in BCC were not necessarily those in the most acidotic group and
      vice versa. The shift in ruminal fermentation variables (principal components
      analysis rankings) and the shift in BCC (automated ribosomal intergenic spacer
      analysis rankings) between pre- and postpartum were not related (n=14;
      R(2)=0.00). It was concluded that not all cows are equally susceptible to RA and
      postpartum shifts in BCC appear to be independent of the differences in the
      severity of RA postpartum.

PMID- 22981586
TI  - Influences of sample interference and interference controls on quantification of
      enterococci fecal indicator bacteria in surface water samples by the qPCR method.
AB  - A quantitative polymerase chain reaction (qPCR) method for the detection of
      enterococci fecal indicator bacteria has been shown to be generally applicable
      for the analysis of temperate fresh (Great Lakes) and marine coastal waters and
      for providing risk-based determinations of water quality at recreational beaches.
      In this study we further examined the applicability of the method for analyses of
      diverse inland waters as well as tropical marine waters from Puerto Rico based on
      the frequencies of samples showing presumptive PCR interference. Interference was
      assessed by salmon DNA sample processing control (SPC) and internal amplification
      control (IAC) assay analysis results and pre-established acceptance criteria of
      <3.0 and <1.5 cycle threshold (Ct) offsets from control samples, respectively.
      SPC assay results were accepted in analyses of 93% of the inland water samples
      whereas the criterion was met at frequencies of 60% and 97% in analyses of
      samples from Puerto Rico in two different years of sampling. The functionality of
      the control assays and their acceptance criteria was assessed on the basis of
      relative recovery estimates of spiked enterococci target organisms extracted in
      the presence of water sample filters and sample-free control filters and was
      supported by observations that recovery estimates from the water sample and
      control filters were substantially different for samples that failed these
      criteria. Through the combined use of the SPC and IAC assays, two presumptive
      types of interference were identified. One type, observed in the tropical marine
      water samples, appeared to primarily affect the availability of the DNA templates
      for detection. The second type, observed in river water samples, appeared to
      primarily affect PCR amplification efficiency. In the presence of DNA template
      interference, adjustments from SPC assay results by the DeltaDeltaCt comparative
      Ct calculation method decreased the variability of spiked enterococci recovery
      estimates and increased the similarity with control filters as compared to
      unadjusted recovery estimates obtained by the DeltaCt calculation method. Use of
      a higher salmon DNA concentration in the extraction buffer also reduced this type
      of interference. The effects of amplification interference were largely reversed
      by dilution of the DNA extracts and even more effectively by the use of an
      alternative, commercial PCR reagent, designed for the analysis of environmental
      samples.

PMID- 22981587
TI  - Low-energy formation of edible nanoemulsions: factors influencing droplet size
      produced by emulsion phase inversion.
AB  - Nanoemulsions can be used for the encapsulation and oral delivery of bioactive
      lipophilic components, such as nutraceuticals and pharmaceuticals. There is
      growing interest in the utilization of low-energy methods to produce edible
      nanoemulsions. In this study, we examined the influence of system composition and
      preparation conditions on the formation of edible nanoemulsions by the emulsion
      phase inversion (EPI) method. The EPI method involves titrating an aqueous phase
      (water) into an organic phase (oil+hydrophilic surfactant). The influence of oil
      type, surfactant type, surfactant-to-oil ratio (SOR), and initial surfactant
      location on the particle size distributions of the emulsions was studied. The
      droplet size produced by this method depended on: (i) oil type: medium chain
      triglycerides (MCT)<flavor oils (orange and limonene)<long chain triglycerides
      (olive, grape, sesame, peanut and canola oils); (ii) surfactant type: Tween
      80<Tween 20<Tween 85; (iii) surfactant concentration: smaller droplets were
      produced at higher SOR; (iv) surfactant location: surfactant initially in
      oil<surfactant initially in water. The low energy method (EPI) was also compared
      to a high energy method (microfluidization). Small droplets (d<160 nm) could be
      produced by both methods, but much less surfactant was needed for the high energy
      method (SOR>=0.1) than the low energy method (SOR>=0.7).

PMID- 22981588
TI  - In situ synthesis of gold nanoparticles in exponentially-growing layer-by-layer
      films.
AB  - In situ synthesis of inorganic nanoparticles (NPs) in polyelectrolytes
      multilayers (PEMs) has recently gained much attention. Due to the versatility of
      their composition, PEMs offer a unique opportunity to synthesize a variety of
      NPs. So far, mostly cationic precursors have been used and only few studies have
      investigated the possibility of using amine groups to bind anionic precursors.
      Here, we use exponentially growing poly(L-lysine)/hyaluronan (PLL/HA) films as a
      nanoreservoir to bind and sequester aurochlorate (AuCl(4)(-)) anions thanks to
      the large number of free amine groups. The polypeptide-polysaccharide reactive
      template enabled the formation in a spatially-confined environment of gold NP at
      a very high yield. The synthesized gold NPs were homogenous and well-dispersed in
      the nanocomposite. Importantly, there was no particular effect of the film-ending
      layer (either PLL or HA). The largest particles of ~9 nm and the largest amount
      of gold were obtained at acidic pH of 3. When the pH was increased, smaller and
      more numerous NPs were synthesized but the total amount of gold was lower. Based
      on UV-visible spectrometry, FTIR and TEM data, we finally propose a scheme for
      the mechanism of gold NPs formation, in which several groups of PLL and HA
      contribute to the binding of gold ions, the nucleation and growth of NPs, and
      their stabilization in the "bulk" of the film.

PMID- 22981589
TI  - Comment on: "FT-IR, FT-Raman and UV spectral investigation; computed frequency
      estimation analysis and electronic structure calculations on 1-nitronaphthalene"
      by M. Govindarajan and M. Karabacak [Spectrochim. Acta A 85 (2012) 251-260].
AB  - The title paper [1] incorrectly establishes that, in gas phase the global minimum
      energy structure of 1-nitronaphthalene is planar (C(s) symmetry). By contrast,
      present calculations indicate that the planar C(s) form is an unstable structure
      on the potential energy surface, exhibiting an imaginary vibrational wavenumber
      value corresponding to the torsional mode of the nitro group around the C-N bond.
      At the B3LYP/6-311++G(d,p) level of calculation the global minimum energy
      structure of 1-nitronaphthalene in gas phase has a non-planar geometry,
      characterized by O-N-C-C dihedral angles of ca. 30 degrees  and lying 0.35
      kcal/mol below the C(s) form.

PMID- 22981590
TI  - Testing a new analytical approach for determination of vibrational transition
      moment directions in low symmetry planar molecules: 1-D- and 2-D-naphthalene.
AB  - A new analytical approach for improving the precision in determination of
      vibrational transition moment directions of low symmetry molecules (lacking
      orthogonal axes) is discussed in this paper. The target molecules are partially
      uniaxially oriented in nematic liquid crystalline solvent and are studied by IR
      absorption spectroscopy using polarized light. The fundamental problem addressed
      is that IR linear dichroism measurements of low symmetry molecules alone cannot
      provide sufficient information on molecular orientation and transition moment
      directions. It is shown that computational prediction of these quantities can
      supply relevant complementary data, helping to reveal the hidden information
      content and achieve a more meaningful and more precise interpretation of the
      measured dichroic ratios. The combined experimental and theoretical/computational
      method proposed by us recently for determination of the average orientation of
      molecules with C(s) symmetry has now been replaced by a more precise analytical
      approach. The new method introduced and discussed in full detail here uses a
      mathematically evaluated angle between two vibrational transition moment vectors
      as a reference. The discussion also deals with error analysis and estimation of
      uncertainties of the orientational parameters. The proposed procedure has been
      tested in an analysis of the infrared linear dichroism (IR-LD) spectra of 1-D-
      and 2-D-naphthalene complemented with DFT calculations using the scaled quantum
      mechanical force field (SQM FF) method.

PMID- 22981591
TI  - A modified Delphi translation strategy and challenges of International
      Classification for Nursing Practice (ICNP(r)).
AB  - BACKGROUND AND OBJECTIVES: Standardized terminology is an important
      infrastructure component of the electronic health record. ICNP((r)) is a systemic
      coding system that can support the development of nursing information systems.
      Translation of the standardized terminology preferred terms into local terms is
      an important first step in the translation process. The purpose of this case
      report is to describe the translation strategy used and challenges faced in
      translating ICNP((r)) Version 2 preferred terms from English to traditional
      Chinese. METHODS: A modified Delphi strategy using forward translation and expert
      consensus was conducted to facilitate semantic and cultural translation and
      validation of the ICNP((r)) and to make the process generalizable. A nursing
      informatics expert completed the initial forward translation. Five nursing
      experts with rich clinical and academic experiences joined this process and
      validated the initial translation. The nursing experts' consensus was then used
      to finalize the traditional Chinese terms. RESULTS: A total of 1863 preferred
      terms from the ICNP((r)) Version 2 were translated from English into traditional
      Chinese. Majority agreement from two or more nursing experts was achieved for
      98.3% (n=1832) of the preferred term translations. Less than 2% (n=31) of terms
      had no majority agreement. Translation challenges include the following: (1)
      changes in code structure of preferred terms from the ICNP((r)) beta2 version to
      Verson 2, (2) inability to identify resources to complete the translation that
      fully met ICNP recommendations for terminology translators, (3) ambiguous
      preferred term descriptions, and (4) ambiguous preferred term names. CONCLUSIONS:
      Most of the ICNP((r)) Version 2 preferred terms were translated from English into
      traditional Chinese with majority consensus. For the terms without consensus, we
      recommend that all synonyms be included in the ICNP((r)) translation. In
      countries like Taiwan where nursing education occurs in English, it is
      recommended that English terms are displayed along with the translated official
      language to help nurses to interpret and use the terminology correctly.

PMID- 22981592
TI  - The translaminar pressure gradient in sustained zero gravity, idiopathic
      intracranial hypertension, and glaucoma.
AB  - Papilledema has long been associated with elevated intracranial pressure.
      Classically, tumors, idiopathic intracranial hypertension, and obstructive
      hydrocephalus have led to an increase in intracranial pressure causing optic
      nerve head edema and observable optic nerve swelling. Recent reports describe
      astronauts returning from prolonged space flight on the International Space
      Station with papilledema (Mader et al., 2011) [1]. Papilledema has not been
      observed in shorter duration space flight. Other recent work has shown that the
      difference in intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFp)
      may be very important in the pathogenesis of diseases of the optic nerve,
      especially glaucoma (Berdahl and Allingham, 2009; Berdahl, Allingham, et al.,
      2008; Berdahl et al., 2008; Ren et al., 2009; Ren et al., 2011) [2-6]. The
      difference in IOP and CSFp across the lamina cribrosa is known as the
      translaminar pressure difference (TLPD). We hypothesize that in zero gravity, CSF
      no longer pools in the caudal spinal column as it does in the upright position on
      earth. Instead, CSF diffuses throughout the subarachnoid space resulting in a
      moderate but persistently elevated cranial CSF pressure, including the region
      just posterior to the lamina cribrosa known as the optic nerve subarachnoid space
      (ONSAS). This small but chronically elevated CSFp could lead to papilledema when
      CSFp is greater than the IOP. If the TLPD is the cause of optic nerve head edema
      in astronauts subjected to prolonged zero gravity, raising IOP and/or orbital
      pressure may treat this condition and protect astronauts in future space travels
      from the effect of zero gravity on the optic nerve head. Additionally, the same
      TLPD concept may offer a deeper understanding of the pathogenesis and treatment
      options of idiopathic intracranial hypertension (IIH), glaucoma and other
      diseases of the optic nerve head.

PMID- 22981593
TI  - Possible link between the synthesis of GR alpha isoforms and eIF2 alpha
      phosphorylation state.
AB  - Glucocorticoid hormones regulate numerous physiological processes and are widely
      used in the treatment of inflammation, autoimmune disease and cancer.
      Glucocorticoid receptor (GR) - a transcription factor, derived from a single
      gene, is responsible for the diverse actions of glucocorticoids. It was shown
      that GR gene gives rise a variety of mRNA species that produces several protein
      isoforms, among them GRalpha is the most abundant. In addition, GRalpha N-end
      truncated protein isoforms (A, B, C, D) are generated by translational
      mechanisms. As it was found that the ratio between the translational isoforms
      amounts varied in different tissues and cell lines and distinct isoforms could
      control transcription of different sets of genes, molecular mechanisms
      underlining the synthesis of translational GRalpha isoforms are of great
      interest. It was considered that GRalpha isoform A is translated by a
      conventional linear scanning, isoform B is translated by leaky scanning, isoform
      C is translated by leaky scanning and ribosomal shunt whereas translation of
      isoform D occurs through ribosomal shunt only. Since the sequence organization of
      GRalpha mRNA strongly resembles the cases of ATF4 or ATF5, the well-known
      examples of reinitiation-dependent synthesis of functional isoforms, we
      hypothesize that translation of isoform C could be controlled by reinitiation
      mechanism also. If this assumption is correct, the ratio between GRalpha N-end
      isoforms could depend on the eIF2alpha phosphorylation state that could provide
      an additional connection between the GR and cellular stresses. We believe that
      this hypothesis could be of interest to plan more robust experiments or for
      better interpretation of available data.

PMID- 22981594
TI  - Reciprocal influence of masticatory apparatus, craniofacial structure and whole
      body homeostasis.
AB  - There are evidences that the evolution into Homo erectus was partially induced by
      masticatory muscular dystrophy caused by a gene mutation, which in turn increased
      brain capacity and led to bipedalism. It is generally accepted that the
      morphology and function of mammalian skull are partially controlled by epigenetic
      mechanisms. Archeologic evidences support that the masticatory apparatus have
      influenced the mechanical stress distribution in hominin skull, and consequently
      changed craniofacial morphology and function. Even after evolution into H.
      erectus, alterations in food properties by civilization and cultural preferences
      have caused modification of human masticatory pattern and accordingly
      craniofacial structure. Since there are evidences that prehuman and human
      masticatory apparatus has been influenced the craniofacial and whole body
      morphology and function, this apparatus in turn might influence whole body
      homeostasis. Plausible reciprocal influencing mechanisms of the masticatory
      apparatus on the whole body homeostasis might be (1) direct mechanical influence
      on the craniofacial structure, (2) distortion of cerebrospinal fluid circulation,
      and/or (3) several neural/humoral routes. Based on these backgrounds, the
      hypothesis of the present study is that the morphology and function of
      masticatory apparatus influence the whole body homeostasis and these interactions
      are reciprocal. Therefore, human masticatory apparatus, at the present time,
      should be kept in its physiological status to maintain the whole body
      homeostasis. We recommend basic and clinical approaches to confirm this
      hypothesis.

PMID- 22981595
TI  - Could cheese be the missing piece in the French paradox puzzle?
AB  - The low rates of cardiovascular mortality which have existed in France for
      decades despite high saturated fat consumption constitute an epidemiological
      phenomenon called the "French paradox". This phenomenon was originally attributed
      to consumption of red wine and its major constituent resveratrol. However, recent
      studies have revealed the limitations of this link outside France. These
      observations indicate that consumption of red wine alone cannot explain the
      paradox and perhaps some other constituents of the typical French diet could be
      responsible for reduced cardiovascular mortality. We hypothesize that cheese
      consumption, especially of molded varieties, may contribute to the occurrence of
      the "French paradox". This assumption is well supported by newly discovered facts
      revealing the positive effect of cheese ingestion on lipoprotein turnover and
      plasma lipid profile, haemorheological parameters and inflammatory status. Recent
      advances in cheese proteomics have allowed the identification and isolation of
      novel peptides capable of inhibiting the angiotensin-converting enzyme which
      controls systemic blood pressure. A complex time-dependent enzymatic
      transformation of the cheese core controlled by probiota, temperature and
      humidity during the ripening process has been shown to result in the formation of
      substances reducing major pro-inflammatory markers and cytokines (C-reactive
      protein, interleukin 6, tumor necrosis factor alpha). Molded cheeses, including
      Roquefort, may be even more favorable to cardiovascular health due to the
      presence of secondary metabolites produced by Penicillium roqueforti and other
      fungi. Among them are andrastins A-D and roquefortine, whose ability to inhibit
      cholesterol biosynthesis and bacterial growth may be a key mechanism in the
      prevention of cardiovascular disease.

PMID- 22981596
TI  - Impaired autophagy leads to abnormal dendritic cell-epithelial cell interactions.
AB  - BACKGROUND AND AIMS: Dendritic cells (DC) are key players in intestinal immunity,
      as these cells can direct the immune response to either a tolerogenic or an
      immunogenic phenotype. In the intestine, DC sample and process luminal antigens
      by protruding dendrites through the epithelial cell layer. At the same time
      barrier integrity is maintained through the continuous formation of tight
      junctions. Aberrations in these interactions may lead to altered antigen sampling
      and improper immune responses. We have recently shown that autophagy, a process
      implicated in the pathogenesis of Crohn's disease, regulates cellular
      interactions in the context of DC and T cells. In this study we aimed to
      determine whether autophagy also regulates DC-epithelial cell interactions and
      whether this influences the ensuing immune response. METHODS: DC were generated
      from peripheral blood monocytes of healthy volunteers. For interaction studies,
      DC were co-cultured with intestinal epithelial cells on the baso-lateral side of
      a transwell insert. Modulation of autophagy was achieved using atg16l1 specific
      siRNA or pharmacological inhibitors. Intraepithelial protrusion of dendrites was
      determined by confocal microscopy. Luminal sampling and DC activation status were
      analyzed by flow cytometry. Protein expression was measured by immunoblotting and
      cytometric bead assay. RESULTS: Adhesion molecules E-cadherin and occludin partly
      localized to autophagosomes and increased autophagy resulted in decreased levels
      of these proteins. Reduced autophagy in either DC, epithelial cells or both
      resulted in the decreased formation of transepithelial protrusions by DC as well
      as a reduction in antigen sampling. Moreover, when autophagy was inhibited in the
      co-culture model, DC expressed increased levels of HLA-DR and costimulatory
      molecule CD86. Furthermore, decreased levels of autophagy resulted in lower IL-10
      production by DC and these cells induced significantly more T-cell proliferation
      in an allogeneic mixed lymphocyte reaction. CONCLUSIONS: In intestinal DC
      epithelial cell interactions, autophagy deficiency leads to decreased antigen
      sampling, increased DC maturation and a more pro-inflammatory type of DC.

PMID- 22981597
TI  - Rapid resolution liquid chromatography (RRLC) analysis of amino acids using pre
      column derivatization.
AB  - A rapid resolution liquid chromatography (RRLC) method was developed for the
      simultaneous determination of 23 amino acids in rat serum after pre-column
      derivatization with 2,4-dinitrofluorobenzene (DNFB). The amino acid derivatives
      were separated on an Agilent Zorbax Eclipse Plus C(18) (4.6 mm*50 mm, 1.8 MUm)
      column at 45 degrees C. Ultraviolet (UV) detection was set at 360 nm. Good
      separation of 23 amino acids was achieved within 10 min with a ternary gradient
      elution of mobile phase at a flow rate of 1.5 mLmin(-1). Calibration curves were
      linear over the range from 1 to 500 MUmolL(-1) with coefficients 0.9962 or better
      for each amino acid. The lower limits of quantification (LLOQ) of all 23 amino
      acids were 1MUmolL(-1) with signal-to-noise (S/N) ratio >=4. Intra- and Inter-day
      precisions, expressed as relative standard deviation (RSD) percentages, were
      ranged from 0.32% to 3.09% and 0.67% to 5.82%, respectively. Finally, it was
      successfully applied to the determination of amino acids in rat serum with
      recoveries ranged from 90.8% to 106.0% and RSD percentages ranged from 1.78% to
      4.68%, respectively. The results showed that the proposed method provided a
      shorter elution time, better resolution and sharper peak shapes for all amino
      acids. Compared with the conventional high performance liquid chromatography
      (HPLC) methods, even some ultra-performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS), the established RRLC method was superior performance.

PMID- 22981598
TI  - Screening for psychosocial distress in patients with long-term home parenteral
      nutrition.
AB  - BACKGROUND & AIMS: Long-term home parenteral nutrition (HPN) may cause distress
      and negatively affect quality of life (QoL). The HPN version of the Distress
      Thermometer and Problem List (DT/PL) was developed to evaluate distress during
      HPN. This study validates the DT/PL, examines referral wish for additional care,
      assesses opinions on the DT/PL, and studies risk factors for distress and
      referral wish. METHODS: Dutch and Scottish patients completed questions on socio
      demographic and HPN-related general characteristics, the DT/PL, referral wish,
      the Hospital Anxiety and Depression Scale, and opinions on the DT. RESULTS: The
      HPN version of the DT/PL seemed valid and the PL sufficiently reliable. Cut-off
      score appeared to be 6. Consequently, 45% of patients were diagnosed as
      clinically distressed. Fifty-three percent had a referral wish. Emotional and
      physical problems were most strongly associated with distress. Not being able to
      work related to elevated distress. Female gender and co-morbidity related to
      referral wish. Opinions on the DT were generally positive. CONCLUSION: The DT/PL
      appears to be a good instrument to regularly gain insight into distress and
      referral wish in HPN patients. Use of the DT/PL facilitates support to patients
      who most need and want it, thus improving quality of care and QoL.

PMID- 22981599
TI  - V-ATPase-mediated phagosomal acidification is impaired by Streptococcus pyogenes
      through Mga-regulated surface proteins.
AB  - Streptococcus pyogenes, a significant bacterial pathogen in humans, interferes
      with the membrane traffic of human neutrophils and survives following
      phagocytosis. The mechanism(s) behind this property is not known, but in contrast
      to wild-type bacteria, mutant bacteria lacking virulence factors regulated by the
      transcriptional regulator Mga, are phagocytosed and killed. In the present work
      we investigated whether differences in phagosomal acidification may contribute to
      this difference. Phagosomal pH in neutrophil-differentiated HL-60 cells was
      studied by fluorescence ratio imaging, and phagosomes containing wild-type S.
      pyogenes bacteria of the M1 serotype exhibited little or no acidification,
      whereas Mga mutant bacteria were found in more acidic phagosomes. With phagosomes
      containing these bacteria, proton delivery was inhibited by adding folimycin, a
      vacuolar-type adenosine triphosphatase (V-ATPase) inhibitor. This inhibitor had
      no effect on phagosomes containing wild-type bacteria, indicating either
      inactivation or removal of V-ATPases by the bacteria. Analysis of isolated
      bacteria-containing phagosomes confirmed the latter scenario and showed a more
      efficient delivery of V-ATPases to phagosomes containing Mga mutant bacteria. The
      results demonstrate that V-ATPase-mediated phagosomal proton delivery is reduced
      during phagocytosis of wild-type S. pyogenes, leading to impaired acidification,
      and that surface proteins of the mga regulon are responsible for this effect.

PMID- 22981600
TI  - Translocon-independent intracellular replication by Pseudomonas aeruginosa
      requires the ADP-ribosylation domain of ExoS.
AB  - Pseudomonas aeruginosa, a significant cause of human morbidity and mortality,
      uses a type 3 secretion system (T3SS) to inject effector toxins into host cells.
      We previously reported that P. aeruginosa uses ADP-ribosyltransferase (ADPr)
      activity of the T3SS effector ExoS for intracellular replication. T3SS translocon
      (DeltapopB)-mutants, which can export, but not translocate effectors across host
      membranes, retained intracellular replication. We hypothesized that secreted
      effectors mediate translocon-independent intracellular replication. Translocon
      mutants of PAO1 lacking one or more of its three known effectors (ExoS, ExoT and
      ExoY) were used. All translocon mutants, irrespective of effectors expressed,
      localized to intracellular vacuoles. Translocon-effector null mutants and
      translocon-exoS mutants showed defective intracellular replication. Mutants in
      exoT, exoY or both replicated as efficiently as translocon mutants expressing all
      effectors. Complementation of translocon-effector null mutants with native exoS
      or a membrane localization domain mutant of exoS, but not the ADPr mutant exoS
      (pUCPexoSE381D), restored intracellular replication, correlating with increased
      bacteria per vacuole. Thus, P. aeruginosa is capable of intravacuolar replication
      that requires ExoS ADPr activity, but not the translocon. These data suggest that
      T3SS effectors can participate in pathogenesis without translocon-mediated
      translocation across host membranes, and that intracellular bacteria can
      contribute to P. aeruginosa pathogenesis within epithelial cells.

PMID- 22981601
TI  - Recombinant trehalose-6-phosphate phosphatase of Brugia malayi cross-reacts with
      human Wuchereria bancrofti immune sera and engenders a robust protective outcome
      in mice.
AB  - Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an
      attractive vaccine candidate because it is present in all the major life stages
      of parasite, but is absent in mammals. We have previously cloned, purified and
      biochemically characterized Bm-TPP. In the present study, we investigated the
      cross-reactivity of recombinant Bm-TPP (r-Bm-TPP) with the sera of human
      bancroftian patients belonging to different disease categories. In silico study
      using bioinformatics tool demonstrated that Bm-TPP is highly immunogenic in
      nature. BALB/c mice administered with r-Bm-TPP alone or in combination with
      Freund's complete adjuvant (FCA) generated a strong IgG response. Further
      investigations on the antibody isotypes showed generation of a mixed T helper
      cell response which was marginally biased towards Th1 phenotype. r-Bm-TPP with or
      without adjuvant lead to significantly increased accumulation of CD4+ and CD8+ T
      cells in the spleen of infected mice and increased the activation of peritoneal
      macrophages. Additionally, r-Bm-TPP enhanced the production of both
      proinflammatory (IL-2, IFN-gamma) and anti-inflammatory (IL-4, IL-10) cytokines
      and mice immunized with r-Bm-TPP alone or in combination with FCA showed 54.5%
      and 67% protection respectively against B. malayi infective larvae challenge.
      Taken together, our findings suggest that Bm-TPP is protective in nature and
      might be a potential candidate for development of vaccine against lymphatic
      filarial infections.

PMID- 22981602
TI  - Shielding artificially increases the attenuation of water: study of CT gradient
      attenuation induced by shielding (CT GAINS).
AB  - RATIONALE AND OBJECTIVES: Quantitatively analyze the computed tomography (CT)
      attenuation effects caused by bismuth shields, which are used to reduce
      superficial organ dose. MATERIALS AND METHODS: The solid water uniformity section
      of the American College of Radiology CT phantom was scanned with a modified chest
      CT protocol. Scans were performed with a bismuth breast shield in multiple
      configurations, emphasizing three clinically relevant orientations. Attenuation
      effects were measured as changes in mean Hounsfield unit (HU) values of equal
      midsagittal regions of interest (ROI). Multiple statistical techniques were used
      in regression analysis. RESULTS: Bismuth shielding resulted in significant
      positive shifts of the expected Hounsfield unit values. The mean nonshielded CT
      attenuation was -0.16 +/- 0.75 HU. Based on the clinically relevant ROI distance
      from the shield (~3-16 cm), the shielded values ranged from 43.8-4 HU, 45.8-10.1
      HU, and 50.6-4.5 HU for shields 1, 2, and 3, respectively. All shield
      configurations displayed a statistically significant shift (P < .0001) at all
      distance ranges. The best fitting regression model was a quadratic function of
      distance versus logarithmic function of HU. A prediction table of the approximate
      shift in water HU values as a function of ROI distance from the shield was
      generated per shield type from their respective close-fitting regressions.
      CONCLUSIONS: The data support the claim that bismuth shields increase the
      attenuation of water, which can cause inaccurate characterization of simple
      fluid, giving the appearance of complex fluid or even solid density. However,
      there is potential for anticipation of the attenuation effects to validate
      continued use of these shields for dose reduction.

PMID- 22981603
TI  - Preoperative CT findings of thymoma are correlated with postoperative Masaoka
      clinical stage.
AB  - RATIONALE AND OBJECTIVES: Both preoperative computed tomography (CT) staging and
      postoperative surgical Masaoka clinical staging are of great clinical importance
      for diagnosing thymomas. Our study aimed to investigate the relationships between
      these two staging systems. MATERIALS AND METHODS: This was a retrospective review
      of 129 patients who had undergone thymoma surgery. Helical CT and 16-slice CT
      were performed preoperatively. Surgical findings were evaluated according to the
      Masaoka clinical staging system. RESULTS: A significant association was shown
      between Masaoka clinical staging and CT staging, especially of features including
      tumor size (P = .004), tumor shape (P < .001), tumor density (P < .001), capsule
      completeness (P < .001), and involvement of surrounding tissues (P < .001). Based
      on the CT findings, there were 35.09% of Masaoka stage I patients who had a tumor
      size <5 cm as compared to 14.81% of stage IV patients. Only 8.77% of Masaoka
      stage I patients had a tumor size >=10 cm as compared to 40.74% of stage IV
      patients. In stages III and IV, most tumors were irregularly shaped with an
      uneven density and incomplete capsule. Invasive tumors were more frequently found
      in stages III (81.48%) and IV (88.89%) than in stages I (0%) and II (38.89%). The
      incidence of myasthenia gravis was comparable in different stages. Consistency
      between CT and Masaoka clinical stages was higher in stage I (37.98%) than other
      stages (approximately 10%). CONCLUSION: This study documented a close
      relationship between preoperative CT thymoma staging and postoperative Masaoka
      clinical staging. Thus, preoperative CT findings can be beneficial for
      determining the proper management and prognosis of thymoma patients.

PMID- 22981604
TI  - Comparison of T1rho, dGEMRIC, and quantitative T2 MRI in preoperative ACL rupture
      patients.
AB  - RATIONALE AND OBJECTIVES: T1rho, inversion recovery sequence with a gadolinium
      contrast agent (dGEMRIC), and T2 mapping have shown sensitivity toward different
      osteoarthritic-associated compositional changes after joint injury, but have not
      been studied concomitantly in vivo. We hypothesized that these magnetic resonance
      imaging sequences can be used to measure early glycosaminoglycan (GAG) losses and
      collagen disruption in cartilage of anterior cruciate ligament (ACL) rupture
      patients. MATERIALS AND METHODS: Thirteen acute ACL rupture patients were each
      imaged during a 4-hour presurgery workup to acquire a fast-spin-echo-based T1rho
      sequence, a multi-echo spin-echo T2 sequence, and T1-weighted dGEMRIC an average
      of 55.7 days after injury. After acquisition, the three sequences' relaxation
      times were analytically compared. RESULTS: Site-specific differences were
      evinced, but nonsignificant differences in mean relaxation time between layers of
      the same region and sequence were observed (analysis of variance, P < .05).
      Spearman's correlation coefficients of 0.542 (T1rho vs. T2, P < .05), -0.026
      (T1rho vs. dGEMRIC, P = .585) and -0.095 (T2 vs. dGEMRIC, P < .05) were found.
      CONCLUSION: No appreciable focal GAG loss was detected by dGEMRIC, and T2 was
      generally elevated in the early acute phase of blunt trauma injury. In contrast,
      both general and focal elevations in T1rho relaxation times were identified,
      indicating an acute increase in unbound water in the matrix after blunt trauma,
      and show that patient-specific cartilage changes occur within otherwise healthy,
      young patients. Further investigation into each sequence's long-term significance
      is warranted to help clinicians decide which sequence(s) will be the most useful
      for osteoarthritis prognosis given the challenge of concomitantly acquiring all
      three in a busy clinical setting.

PMID- 22981605
TI  - Slits and Robo-2 regulate the coalescence of subsets of olfactory sensory neuron
      axons within the ventral region of the olfactory bulb.
AB  - Olfactory sensory neurons (OSNs) project their axons to second-order neurons in
      the olfactory bulb (OB) to form a precise glomerular map and these stereotypic
      connections are crucial for accurate odorant information processing by animals.
      To form these connections, olfactory sensory neuron (OSN) axons respond to axon
      guidance molecules that direct their growth and coalescence. We have previously
      implicated the axon guidance receptor Robo-2 in the accurate coalescence of OSN
      axons within the dorsal region of the OB (Cho et al., 2011). Herein, we have
      examined whether Robo-2 and its ligands, the Slits, contribute to the formation
      of an accurate glomerular map within more ventral regions of the OB. We have
      ablated expression of Robo-2 in OSNs and assessed the targeting accuracy of axons
      expressing either the P2 or MOR28 olfactory receptors, which innervate two
      different regions of the ventral OB. We show that P2-positive axons, which
      express Robo-2, coalesce into glomeruli more ventrally and form additional
      glomeruli in the OB of robo-2(lox/lox);OMP-Cre mice. We also demonstrate that
      Robo-2-mediated targeting of P2 axons along the dorsoventral axis of the OB is
      controlled by Slit-1 and Slit-3 expression. Interestingly, although MOR28
      positive OSNs only express low levels of Robo-2, a reduced number of MOR28
      positive glomeruli is observed in the OB of robo-2(lox/lox);OMP-Cre mice. Taken
      together, our results demonstrate that Slits and Robo-2 are required for the
      formation of an accurate glomerular map in the ventral region of the OB.

PMID- 22981607
TI  - Effects of SiC nanoparticles orally administered in a rat model: biodistribution,
      toxicity and elemental composition changes in feces and organs.
AB  - BACKGROUND: Silicon carbide (SiC) presents noteworthy properties as a material
      such as high hardness, thermal stability, and photoluminescent properties as a
      nanocrystal. However, there are very few studies in regard to the toxicological
      potential of SiC NPs. OBJECTIVES: To study the toxicity and biodistribution of
      silicon carbide (SiC) nanoparticles in an in vivo rat model after acute (24h) and
      subacute (28days) oral administrations. The acute doses were 0.5, 5, 50, 300 and
      600mg.kg(-1), while the subacute doses were 0.5 and 50mg.kg(-1). RESULTS: SiC
      biodistribution and elemental composition of feces and organs (liver, kidneys,
      and spleen) have been studied by Particle-Induced X-ray Emission (PIXE). SiC and
      other elements in feces excretion increased by the end of the subacute
      assessment. SiC did not accumulate in organs but some elemental composition
      modifications were observed after the acute assessment. Histopathological
      sections from organs (stomach, intestines, liver, and kidneys) indicate the
      absence of damage at all applied doses, in both assessments. A decrease in the
      concentration of urea in blood was found in the 50mg.kg(-1) group from the
      subacute assessment. No alterations in the urine parameters (sodium, potassium,
      osmolarity) were found. CONCLUSION: This is the first study that assesses the
      toxicity, biodistribution, and composition changes in feces and organs of SiC
      nanoparticles in an in vivo rat model. SiC was excreted mostly in feces and low
      traces were retrieved in urine, indicating that SiC can cross the intestinal
      barrier. No sign of toxicity was however found after oral administration.

PMID- 22981606
TI  - Id2a functions to limit Notch pathway activity and thereby influence the
      transition from proliferation to differentiation of retinoblasts during zebrafish
      retinogenesis.
AB  - During vertebrate retinogenesis, the precise balance between retinoblast
      proliferation and differentiation is spatially and temporally regulated through a
      number of intrinsic factors and extrinsic signaling pathways. Moreover, there are
      complex gene regulatory network interactions between these intrinsic factors and
      extrinsic pathways, which ultimately function to determine when retinoblasts exit
      the cell cycle and terminally differentiate. We recently uncovered a cell non
      autonomous role for the intrinsic HLH factor, Id2a, in regulating retinoblast
      proliferation and differentiation, with Id2a-deficient retinae containing an
      abundance of proliferative retinoblasts and an absence of terminally
      differentiated retinal neurons and glia. Here, we report that Id2a function is
      necessary and sufficient to limit Notch pathway activity during retinogenesis.
      Id2a-deficient retinae possess elevated levels of Notch pathway component gene
      expression, while retinae overexpressing id2a possess reduced expression of Notch
      pathway component genes. Attenuation of Notch signaling activity by DAPT or by
      morpholino knockdown of Notch1a is sufficient to rescue both the proliferative
      and differentiation defects in Id2a-deficient retinae. In addition to regulating
      Notch pathway activity, through a novel RNA-Seq and differential gene expression
      analysis of Id2a-deficient retinae, we identify a number of additional intrinsic
      and extrinsic regulatory pathway components whose expression is regulated by
      Id2a. These data highlight the integral role played by Id2a in the gene
      regulatory network governing the transition from retinoblast proliferation to
      terminal differentiation during vertebrate retinogenesis.

PMID- 22981608
TI  - Remission of psoriasis after allogeneic, but not autologous, hematopoietic stem
      cell transplantation.
AB  - Hematopoietic stem-cell transplantation (HSCT) has emerged as an effective
      immunotherapy for several severe autoimmune diseases. A comprehensive search of
      the existing literature was performed for patients with psoriasis and HSCT.
      Nineteen patients have been reported to have psoriasis resolution after
      allogeneic or autologous HSCT. In the allogeneic setting, 10 of 13 were noted to
      have durable remission of their psoriasis with a mean follow-up of 49 months. Two
      cases that did reoccur were only transient. Six patients underwent autologous
      transplantation. Of these, 5 of 6 developed a recurrence of their psoriasis
      within 2 years. Based on a limited number of patients, psoriasis is likely to
      remit after allogeneic HSCT, but it is likely to recur after autologous HSCT.

PMID- 22981609
TI  - Increased treatment-related mortality with additional cisplatin-based
      chemotherapy in patients with nasopharyngeal carcinoma treated with standard
      radiotherapy.
AB  - BACKGROUND AND PURPOSES: We performed a meta-analysis of randomized controlled
      trials (RCTs) to determine the overall risk of treatment-related death associated
      with additional cisplatin-based chemotherapy in patients with nasopharyngeal
      carcinoma treated with standard radiotherapy. MATERIAL AND METHODS: Eligible
      studies included RCTs in which cisplatin-based chemotherapy in combination with
      radiotherapy was compared with radiotherapy alone. Statistical analyses were
      conducted to calculate the summary incidence rates, relative risks (RRs), and 95%
      confidence intervals (CIs) using fixed- or random-effects models based on the
      heterogeneity of included studies. RESULTS: A total of 2829 patients from 13 RCTs
      were included in this study. The overall incidence for treatment-related death in
      chemoradiotherapy and radiotherapy treated patients was 1.7% and 0.8%. Compared
      to radiotherapy alone, radiotherapy plus cisplatin-based chemotherapy
      significantly increased the risk of treatment-related mortality. On subgroup
      analyses, no difference was found in treatment-related mortality between
      different timings of chemotherapy and chemotherapeutic agents. Adding cisplatin
      based chemotherapy was associated with higher incidences of severe acute
      toxicity. CONCLUSIONS: Cisplatin-based chemotherapy plus radiotherapy increased
      the risk of treatment-related death and severe acute toxicity, compared with
      radiotherapy alone. Better management of treatment toxicity might improve the
      therapeutic gain in patients with nasopharyngeal carcinoma.

PMID- 22981610
TI  - Patterns of regional recurrence after curative D2 resection for stage III (N3)
      gastric cancer: implications for postoperative radiotherapy.
AB  - BACKGROUND AND PURPOSE: To analyze patterns of regional recurrence after curative
      gastrectomy and D2 lymph node dissection in patients with stage III (N3) gastric
      cancer. MATERIALS AND METHODS: Between 2004 and 2008, 2918 patients with primary
      gastric cancer underwent D2 resection at a single institution. A retrospective
      review was performed on 382 patients in stage III with N3 disease. Of these, 357
      patients (93.5%) received adjuvant chemotherapy. None of the patients received
      pre- or postoperative radiotherapy. RESULTS: Median follow-up was 56.3 months.
      The 5-year regional failure free-survival (RFFS) rate was 63.6%. Regional failure
      (RF) as any component of first recurrence occurred in 91 patients (23.8%), with
      isolated regional failure occurring in 49 (12.8%). The most commonly involved
      lymph nodes were the No. 16b, No. 16a, No. 12, No. 14, No. 13, and No. 9 nodes.
      RFFS was adversely affected by advanced nodal stage (N3b vs. N3a). The 5-year
      progression-free survival rate was 32.1% and overall survival was 41.5%.
      CONCLUSION: The most prevalent nodal recurrence in patients with advanced gastric
      cancer was in the nodal basin outside the D2 dissection field. Our findings may
      help physicians construct a lymph node target volume for radiation treatment of
      gastric cancer after D2 dissection.

PMID- 22981611
TI  - Association between adult otitis media and nasopharyngeal cancer: a nationwide
      population-based cohort study.
AB  - PURPOSE: To determine whether the diagnosis of otitis media (OM) in adults is
      associated with an increased risk for the subsequent development of
      nasopharyngeal cancer (NPC) using a nationwide population-based retrospective
      study. METHODS AND MATERIALS: We selected 13,513 adult patients that had been
      previously diagnosed with OM between 2000 and 2005 from the Taiwan Longitudinal
      Health Insurance Database 2000 as the study cohort, and randomly extracted the
      data of 135,130 participants matched by sex, age, and baseline year for the
      comparison cohort. The follow-up period was terminated upon developing NPC,
      withdrawal from the national health insurance system, or the end of 2009.
      Cumulative incidences and hazard ratios (HRs) of NPC development were determined.
      RESULTS: The subsequent NPC incidence rates in the OM and comparison cohorts were
      6.41 and 0.58 per 10000 person-years, respectively (adjusted HR, 11.04; 95% CI,
      7.68-5.87; P<0.0001). The NPC risk for males was significantly higher than that
      for females (adjusted HR=3.24; 95% CI, 2.16-4.85). In both female and male
      patients, the diagnosis of OM was associated with a significantly increased risk
      for NPC (adjusted HR, 11.91 vs. 10.78, respectively). Among the OM cohort, 62
      participants were subsequently diagnosed with NPC, with 71% of them occurring
      within 1 year following the diagnosis of OM. However, even after 5-year follow
      up, the OM cohort still displayed a higher risk for NPC (adjusted HR=2.50).
      Stratified by the frequency of OM episodes, more than one episode per year had a
      significantly greater risk of developing NPC, compared with the comparison cohort
      (HR=29.22; 95% CI, 20.19-42.27). CONCLUSION: We found that adult OM is a warning
      sign for the development of NPC in Taiwan, with approximately an 11-fold higher
      risk for adult OM patients. We recommend that OM patients undergo follow-up
      examinations for at least 5 years. To extrapolate our findings, further studies
      are warranted in other areas in which NPC is endemic.

PMID- 22981612
TI  - Small-incision lenticule extraction for moderate to high myopia: Predictability,
      safety, and patient satisfaction.
AB  - PURPOSE: To present initial clinical experience with small-incision lenticule
      extraction for the treatment of moderate to high myopia. SETTING: Department of
      Ophthalmology, Aarhus University Hospital, Aarhus, Denmark. DESIGN: Prospective
      clinical study. METHODS: For small-incision lenticule extraction, an intrastromal
      lenticule was cut with a femtosecond laser and manually extracted without
      creation of a flap. Patients were treated and followed for 3 months. Only 1
      randomly chosen eye of each patient was used in the statistical analyses.
      RESULTS: The study enrolled 144 patients. The mean preoperative spherical
      equivalent was -7.18 diopters (D) +/- 1.57 (SD). Of eyes with emmetropia as
      target refraction, 40% had an uncorrected distance visual acuity of 0.1 logMAR or
      less 1 day after surgery; this increased to 73% at 3 months. The mean corrected
      distance visual acuity (CDVA) improved significantly from -0.01 (logMAR)
      preoperatively to -0.03 3 months postoperatively. None of the 127 eyes lost 2
      lines or more of CDVA and 6 eyes lost 1 line of CDVA after 3 months. In contrast,
      1 eye gained 2 lines and 24 eyes gained 1 line of CDVA. The achieved refraction
      was a mean of -0.09 +/- 0.45 D from the attempted refraction. Of the eyes, 77%
      were within +/-0.50 D and 95% were within +/-1.00 D. Ninety-five percent of the
      patients would recommend the procedure to others. CONCLUSIONS: The refractive
      predictability, safety, and patient satisfaction 3 months after small-incision
      lenticule extraction were high and comparable to results in previous studies of
      femtosecond laser-assisted techniques. FINANCIAL DISCLOSURE: Drs. Hjortdal and
      Asp received travel reimbursement from Carl Zeiss Meditec AG, Jena, Germany. No
      other author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 22981613
TI  - Early clinical outcomes, including efficacy and endothelial cell loss, of
      refractive lenticule extraction using a 500 kHz femtosecond laser to correct
      myopia.
AB  - PURPOSE: To assess the early clinical outcomes, including the efficacy and the
      endothelial cell loss, of femtosecond lenticule extraction using a 500 kHz
      femtosecond laser system to correct myopia. SETTING: Department of Ophthalmology,
      Kitasato University, Kanagawa, Japan. DESIGN: Case series. METHODS: This study
      evaluated eyes with a spherical equivalent of -4.26 diopters (D) +/- 1.39 (SD)
      that had femtosecond lenticule extraction for myopia. Before surgery and 1 week
      and 1, 3, and 6 months after surgery, the safety, efficacy, predictability,
      stability, and adverse events of the surgery were assessed. RESULTS: The study
      enrolled 38 eyes of 20 patients. The uncorrected distance visual acuity and
      corrected distance visual acuity 6 months after surgery were -0.14 +/- 0.10
      logMAR and -0.21 +/- 0.09 logMAR, respectively. The safety index was 0.96 +/-
      0.19 and the efficacy index, 0.82 +/- 0.17. At 6 months, all eyes were within +/
      0.50 D of the targeted correction. The mean manifest refraction change from 1
      week to 6 months was 0.02 +/- 0.28 D. The endothelial cell density was 2814 +/-
      199 cells/mm(2) preoperatively and 2762 +/- 213 cells/mm(2) postoperatively; the
      change was not significant (P = .32, Wilcoxon signed-rank test). No vision
      threatening complications occurred during the observation period. CONCLUSIONS:
      Femtosecond lenticule extraction performed well in the correction of myopia.
      Neither significant endothelial cell loss nor serious complications occurred
      throughout the 6-month follow-up, suggesting femtosecond lenticule extraction is
      a viable surgical option to treat myopic eyes. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 22981614
TI  - Scheimpflug photography-based clinical characterization of the correlation of the
      corneal shape between the anterior and posterior corneal surfaces in the normal
      human eye.
AB  - PURPOSE: To evaluate the correlation of the mean curvature and shape factors
      between both corneal surfaces for different corneal diameters measured with a
      Scheimpflug photography-based system. SETTING: Vissum Corporation, Alicante,
      Spain. DESIGN: Case series. METHODS: Randomly selected healthy normal eyes had a
      comprehensive ophthalmologic examination including anterior segment analysis with
      the Sirius system as follows: anterior and posterior mean corneal radius for 3.0
      mm, 5.0 mm, and 7.0 mm; anterior and posterior mean shape factor for 4.5 mm and
      8.0 mm; central (CCT) and minimum corneal thickness; and anterior chamber depth
      (ACD). RESULTS: The study enrolled 117 eyes (117 subjects; aged 7 to 80 years).
      The mean anterior mean corneal radius:posterior mean corneal radius ratio was
      1.19 (range 1.12 to 1.27) for all corneal diameters (P = .86). The correlation
      coefficient between the anterior and posterior mean corneal radius was 0.85 or
      more for all corneal diameters. The anterior mean shape factor:posterior mean
      shape factor ratio for the 2 corneal diameters analyzed was approximately 1
      (range 0.45 to 4.03). The correlations between anterior and posterior mean shape
      factors were extremely poor and not significant. Multiple regression analysis
      showed that the central posterior mean corneal radius was significantly
      correlated with the anterior mean corneal radius, CCT, and spherical equivalent
      (R(2) = 0.77, P<.01). CONCLUSIONS: Central posterior corneal curvature could be
      predicted from the anterior corneal curvature, pachymetry, and the refractive
      status of the eye but not from the corneal shape factor. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 22981615
TI  - Elemental diet therapy for pouchitis following restorative proctocolectomy for
      ulcerative colitis.

PMID- 22981616
TI  - Infliximab for treatment of pyoderma gangrenosum with ulcerative colitis.

PMID- 22981617
TI  - High frequency of antiviral drug resistance and non-B subtypes in HIV-1 patients
      failing antiviral therapy in Cuba.
AB  - BACKGROUND: Emergence of HIV-1 drug resistance may limit the sustained benefits
      of antiretroviral therapy (ART) in settings with limited laboratory monitoring
      and drug options. OBJECTIVES: Surveillance of drug resistance and subtypes in HIV
      1 patients failing ART in Cuba. STUDY DESIGN: This study compiled data of ART
      experienced HIV-1 patients attending a clinical center in Havana in 2003 and 2009
      2011. The first period included results of a cross-sectional study, whereas in
      the second period genotyping was performed as part of routine care. Drug
      resistance mutations and levels were determined using HIVdb version 6.0.9.
      RESULTS: Seventy-six percent received solely ART containing at least 3 drugs, of
      which 79.1% ever receiving unboosted protease inhibitors (PI). Patients from 2009
      to 2011 were longer treated and exposed to more ART regimens. Subtype B (39%) and
      CRF19_cpx (18%) were the most prevalent genetic forms. Subtype distribution did
      not change significantly between both periods, except for BG recombinants that
      increased from 6% to 14%. Nucleoside reverse transcriptase inhibitor (NRTI), non
      nucleoside RTI (NNRTI) and PI mutations were present in 69.5%, 54.8% and 44.4%.
      Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR)
      were detected in 31.8%, 37.9%, 18.5% and 15.4%. FCR to NRTI, NNRTI, PI and MDR
      were present in 9.8%, 14.1%, 0%, 0% after first-line failure and in 19.8%, 20.8%,
      2.9% and 2.9% after second-line failure. CONCLUSIONS: Our study found a high
      prevalence of drug resistance and supports the need for appropriate laboratory
      monitoring in clinical practice and access to drug options in case of virological
      failure.

PMID- 22981618
TI  - An outbreak of HIV-1 BC recombinants in Southern Italy.
AB  - BACKGROUND: In Western Europe, a previously subtype B HIV-1 restricted area, BC
      recombinants have been rarely reported. OBJECTIVE: To describe an outbreak of HIV
      1 BC recombinants in southern Italy. STUDY DESIGN: We analyzed pol
      (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1
      infected patients during the years 2009-2011. For phylogenetic relationships,
      sequences were aligned to the most recent reference data set from the Los Alamos
      database using BioEdit (version 7.1.3). The resulting alignment was analyzed with
      the Phylip package (version 3.67) building a neighbor-joining tree based on the
      Kimura two-parameter substitution model. The reliability of the tree topology was
      assessed through bootstrapping using 1000 replicates. The recombination pattern
      was characterized using SimPlot 3.5.1 and SplitsTree 4. RESULTS: At phylogenetic
      analysis, 22 (16.2%) isolates whose sequences were not unequivocally assigned to
      a pure subtype or known CRF, formed a distinct monophyletic clade (100% of
      bootstrap value). For these isolates, the recombination analysis identified a BC
      mosaic pattern with two breakpoints at positions 2778+/-5 and 3162+/-8 (HXB2
      numbering) which differed from those of known BC CRFs. All patients from whom
      these sequences were derived were highly educated youth Italians, 91% males and
      82% MSM. Sequences of pol integrase, gp120 and gp41 from these same patients were
      classified as C subtype. CONCLUSIONS: This outbreak which further reflects the
      increasing heterogeneity of HIV epidemic in our country is the first report of an
      Italian outbreak of a BC recombinant, possibly a novel candidate CRF.

PMID- 22981619
TI  - Down-regulation of Poleta expression leads to increased DNA damage, apoptosis and
      enhanced S phase arrest in L-02 cells exposed to hydroquinone.
AB  - DNA polymerase eta (Poleta), the product of the xeroderma pigmentosum variant
      gene, is required for translesion DNA synthesis, and plays a pivotal role in
      preventing genome instability after DNA damage induced by genotoxic agents.
      Studies have previously suggested a link between Poleta and susceptibility to
      hydroquinone (HQ)-induced toxicity. To further address the role of Poleta in the
      response of L-02 cells to HQ, we employed RNA interference to silence Poleta
      expression in L-02 cells and examined the susceptibility of these Poleta
      deficient cells to the toxic effects of HQ. In this study, cell survival rate was
      determined using the MTT assay, DNA damage was determined by the Comet assay,
      apoptosis and cell cycle distribution were determined using flow cytometry, the
      mRNA expression levels of Poleta were determined by real-time PCR, and the
      protein expression levels of Poleta and gamma-H2AX were determined by Western
      blot, gamma-H2AX foci were visualized by confocal laser scanning fluorescence
      microscopy after cells were exposed to HQ at various concentrations for 24h in
      vitro. The results showed that stable Poleta-knockdown cells were successfully
      constructed and more than 80% inhibition of Poleta expression was confirmed. The
      results also showed that down-regulation of Poleta led to a decrease in cell
      proliferation and an enhanced susceptibility to HQ-induced cytotoxicity. Poleta
      deficient cells were 2-fold more sensitive to HQ when compared with nonspecific
      siRNA control cells. Moreover, Poleta-silenced L-02 cells treated with HQ
      displayed an increased level of DNA double-strand breaks as measured by olive
      tail moment, and an elevated DNA damage response as indicated by the induction of
      gamma-H2AX. In addition, knockdown of Poleta resulted in more enhanced apoptosis
      and more pronounced S phase arrest following HQ treatment. Together, these
      results show that Poleta plays an important role in the response of L-02 cells to
      HQ-induced DNA damage.

PMID- 22981620
TI  - Real-time concurrent monitoring of apoptosis, cytosolic calcium, and mitochondria
      permeability transition for hypermulticolor high-content screening of drug
      induced mitochondrial dysfunction-mediated hepatotoxicity.
AB  - A quantitative high-content screening (HCS) was suggested for the real-time
      monitoring of drug-induced mitochondrial dysfunction-mediated hepatotoxicity.
      This HCS is very advantageous in that it allows simultaneous observation of drug
      induced activations of hepatotoxic pathways using hypermulticolor cellular
      imaging. The mitochondrial permeability transition (MPT), cytosolic calcium, and
      caspase-3 were selected as functional markers to verify drug-induced
      hepatotoxicity and were concurrently monitored in HepG2 cells in a real-time
      manner. Nefazodone, tolcapone, and troglitazone caused mitochondrial dysfunction
      and subsequent apoptotic HepG2 cell death in addition to marked cytosolic calcium
      increase. On the other hand, extrinsic pathway-mediated apoptotic cell death was
      monitored when HepG2 cells were treated with piroxicam. It was found that
      piroxicam-treated HepG2 cells showed apoptotic cell death without the MPT
      formation, while a cytosolic calcium increase was clearly observed. This finding
      was confirmed by the caspase-8 inhibition assay. These results demonstrated the
      unique potential of real-time hypermulticolor HCS to screen hepatotoxic drugs at
      the in vitro stage rather than the later in vivo stage based on an animal model
      and to ultimately reduce the probability of drug failure.

PMID- 22981621
TI  - Improved cellulase production via disruption of PDE01641 in cellulolytic fungus
      Penicillium decumbens.
AB  - To investigate the function of PDE01641, the homologue of Neurospora crassa
      NCU05137, during cellulase production in Penicillium decumbens, the PDE01641
      encoding gene was knocked out in the present work. The PDE01641 deletion mutant
      showed enhanced cellobiohydrolase activity and beta-glucosidase activity compared
      to the parental strain 114-2. Increased transcription of the main cellulase and
      hemicellulase genes in DeltaPDE01641 gave evidence that PDE01641 might affect the
      process associated with the regulation of cellulolytic enzymes expression.
      Furthermore, the deletion of PDE01641 from the genome of hypercellulolytic
      industrial strain JU-A10-T resulted in 36% and 80% increase in cellulase activity
      and hemicellulase activity respectively. These results revealed that PDE01641
      plays an important role in the regulation of cellulolytic enzyme production in P.
      decumbens, and the engineering strain constructed in this work could be
      potentially used in bioenergy production.

PMID- 22981622
TI  - Analysis of Vis-NIR spectra changes to measure the inflammatory response in the
      nasal mucosal region of influenza A and B virus-infected patients.
AB  - BACKGROUND: Human influenza A and B viruses cause severe seasonal respiratory
      tract infections, especially in infants and young children. Influenza A and B
      viruses have been reported to produce different symptoms and/or severity in
      infected patients, although these remain inconclusive. OBJECTIVES AND STUDY
      DESIGN: In this study, non-invasive visible and near-infrared (Vis-NIR)
      spectroscopy was used for comparative analysis of the inflammatory response to
      influenza A and B virus infections, by measuring changes in water peak (970 nm)
      spectra collected from patient nasal mucosal regions. RESULTS: The results
      suggested that infection with influenza B virus induced more severe inflammatory
      responses in the nasal mucosal region than influenza A virus. CONCLUSIONS: These
      are the first data showing different inflammatory responses to influenza A and B
      viruses at the sites of virus infection.

PMID- 22981623
TI  - First WHO International Reference Panel containing hepatitis B virus genotypes A
      G for assays of the viral DNA.
AB  - BACKGROUND: WHO International Standards (IS) are provided for the calibration and
      validation of diagnostic and screening assays, e.g. for hepatitis B virus (HBV).
      HBV forms numerous subgenotypes and the current IS for HBV DNA reflects
      subgenotype A2. OBJECTIVE: A reference panel with the most prevalent subgenotypes
      should facilitate evaluation of genotype-specific detection efficiencies. STUDY
      DESIGN: 215 HBV positive plasma samples collected worldwide were characterized
      for HBV markers and sequenced. Fifteen subgenotype A1, A2, B2, B4, C2, D1, D3, E,
      F2 and G samples were selected for the panel. The lyophilized samples were tested
      in parallel with the IS in an international collaborative study with 16
      laboratories using 13 different nucleic acid amplification techniques (NATs).
      RESULTS: Eight of 13 NAT had a HBV DNA detection efficiency which was independent
      of the genotype and consistent with the IS, while with five assays, certain
      deviations were noted, particularly with genotype F which was under quantitated
      or even missed by three assays. The panel was accepted by the WHO as the "1st WHO
      International Reference Panel for HBV Genotypes for HBV NAT-Based Assays".
      CONCLUSIONS: The evaluation of HBV DNA assays should include many different
      genotypes. The WHO Reference Panel is universally available for manufacturers of
      HBV DNA assays, diagnostic laboratories and control authorities to facilitate
      standardized validation of HBV genotype specific detection efficiency of both
      diagnostic (quantitative and qualitative) and screening NAT assays.

PMID- 22981624
TI  - Confirmation of endotracheal tube position during resuscitation by bedside
      ultrasonography.

PMID- 22981625
TI  - The authors respond.

PMID- 22981626
TI  - Patient anxiety may influence the efficacy of ED pain management.
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence of anxiety and
      rates of anxiety treatment in emergency department (ED) patients presenting with
      pain-related complaints. METHODS: We prospectively evaluated patients in an urban
      academic tertiary care hospital ED from 2000 through 2010. We enrolled a
      convenience sample of adult patients presenting with pain and recorded patient
      complaint, medication administration, satisfaction, and pain and anxiety scores
      throughout their stay. We stratified patients into 4 different groups according
      to anxiety score at presentation (0, none; 1-4, mild; 5-7, moderate; 8-10,
      severe). RESULTS: We enrolled 10 664 ED patients presenting with pain-related
      complaints. Patients reporting anxiety were as follows: 25.7%, none; 26.1%, mild;
      23.7%, moderate; and 24.5%, severe. Although 48% of patients described moderate
      to severe anxiety at ED presentation and 60% were willing to take a medication
      for anxiety, only 1% received anxiety treatment. Thirty-five percent of patients
      still reported moderate/severe anxiety at discharge. Severe anxiety at ED
      presentation was associated with increased demand for pain medication (odds ratio
      [OR], 1.40; 95% confidence interval [CI], 1.10-1.79) and anxiety medication (OR,
      4.34; 95% CI, 3.68-5.11) during the ED stay and decreased satisfaction with the
      treatment of pain (beta coefficient = -0.328; P < .001). After adjusting for age,
      sex, and presentation pain scores, patients who reported severe anxiety were more
      likely to receive an analgesic (OR, 1.33; 95% CI, 1.19-1.50) and an opioid (OR,
      1.25; 95% CI, 1.11-1.41) during the ED stay. CONCLUSION: Anxiety may be
      underrecognized and undertreated in patients presenting with pain-related
      complaints. Patients reporting severe anxiety were less likely to report
      satisfaction with the treatment of their pain, despite higher rates of analgesic
      administration.

PMID- 22981628
TI  - Fungal contribution to nitrous oxide emissions from cattle impacted soils.
AB  - Microscopic soil fungi isolated from arable, grassland and forest soils have been
      suggested as producers of nitrous oxide (N(2)O). The aim of this work was to
      screen the capabilities for N(2)O production of microscopic fungi originating in
      the pasture soils of a cattle overwintering area with three levels of cattle
      impact intensity. In total, 36 fungal species from 11 genera were isolated during
      a 2-year study, and production of N(2)O under laboratory conditions was confirmed
      in 23 species (64%). Species belonging to the genera Fusarium, Penicillium,
      Monographella, Acremonium, Gibberella, Eurotium, and Pseudallescheria were found
      to be the most potent N(2)O-producers. Different N(2)O production patterns and
      wide variations in production rates, ranging from 1 to 150 MUg N(2)O-Nd(-1), were
      observed, resulting in the transformation of 0.2-18.4% of the initial NO(2)(-)-N
      present in the cultivation medium. The data revealed distinct soil fungal
      communities in the different sections of the cattle overwintering area, and
      indicate a significant effect of cattle overwintering on the composition of soil
      fungal consortia. These observations confirm the importance of soil fungi in
      total N(2)O fluxes from grazed grassland ecosystems.

PMID- 22981629
TI  - Occurrence of arsenic species in algae and freshwater plants of an extreme arid
      region in northern Chile, the Loa River Basin.
AB  - This study reports data on arsenic speciation in two green algae species
      (Cladophora sp. and Chara sp.) and in five aquatic plants (Azolla sp.,
      Myriophyllum aquaticum, Phylloscirpus cf. desserticola, Potamogeton pectinatus,
      Ruppia filifolia and Zannichellia palustris) from the Loa River Basin in the
      Atacama Desert (northern Chile). Arsenic content was measured by Mass
      spectrometry coupled with Inductively Coupled Plasma (ICP-MS), after acidic
      digestion. Liquid chromatography coupled to ICP-MS was used for arsenic
      speciation, using both anionic and cationic chromatographic exchange systems.
      Inorganic arsenic compounds were the main arsenic species measured in all
      samples. The main arsenic species in the extracts of freshwater algae and plants
      were arsenite and arsenate, whereas glycerol-arsenosugar (gly-sug),
      dimethylarsinic acid (DMA) and methylarsonic acid (MA) were present only as minor
      constituents. Of the samples studied, algae species accumulated more arsenic than
      aquatic plants. Total arsenic content ranged from 182 to 11100 and from 20 to 248
      mg As kg(-1) (d.w.) in algae and freshwater plants, respectively. In comparison
      with As concentration in water samples, there was hyper-accumulation (>0.1% d.w.)
      in Cladophora sp.

PMID- 22981627
TI  - The future of human DNA vaccines.
AB  - DNA vaccines have evolved greatly over the last 20 years since their invention,
      but have yet to become a competitive alternative to conventional protein or
      carbohydrate based human vaccines. Whilst safety concerns were an initial
      barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when
      compared to protein vaccines. A wide variety of strategies have been developed to
      optimize DNA vaccine immunogenicity, including codon optimization, genetic
      adjuvants, electroporation and sophisticated prime-boost regimens, with each of
      these methods having its advantages and limitations. Whilst each of these methods
      has contributed to incremental improvements in DNA vaccine efficacy, more is
      still needed if human DNA vaccines are to succeed commercially. This review
      foresees a final breakthrough in human DNA vaccines will come from application of
      the latest cutting-edge technologies, including "epigenetics" and "omics"
      approaches, alongside traditional techniques to improve immunogenicity such as
      adjuvants and electroporation, thereby overcoming the current limitations of DNA
      vaccines in humans.

PMID- 22981630
TI  - Attenuation of acute nitrogen mustard-induced lung injury, inflammation and
      fibrogenesis by a nitric oxide synthase inhibitor.
AB  - Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the
      respiratory tract. Injury is associated with increased expression of inducible
      nitric oxide synthase (iNOS). In these studies we analyzed the effects of
      transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary
      toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control.
      Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d-28 d later
      and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in
      progressive histopathological changes in the lung including multifocal lesions,
      perivascular and peribronchial edema, inflammatory cell accumulation, alveolar
      fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This
      was correlated with trichrome staining and expression of proliferating cell
      nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese
      superoxide dismutase (Mn-SOD) was also increased in the lung following NM
      exposure, along with levels of protein and inflammatory cells in BAL, consistent
      with oxidative stress and alveolar-epithelial injury. Both classically activated
      proinflammatory (iNOS+ and cyclooxygenase-2+) and alternatively activated
      profibrotic (YM-1+ and galectin-3+) macrophages appeared in the lung following NM
      administration; this was evident within 1d, and persisted for 28 d. AG
      administration (50 mg/kg, 2*/day, 1d-3 d) abrogated NM-induced injury, oxidative
      stress and inflammation at 1d and 3d post exposure, with no effects at 7 d or 28
      d. These findings indicate that nitric oxide generated via iNOS contributes to
      acute NM-induced lung toxicity, however, transient inhibition of iNOS is not
      sufficient to protect against pulmonary fibrosis.

PMID- 22981631
TI  - Signal transduction via the T cell antigen receptor in naive and effector/memory
      T cells.
AB  - T cells play an indispensable role in immune defense against infectious agents,
      but can also be pathogenic. These T cells develop in the thymus, are exported
      into the periphery as naive cells and participate in immune responses. Upon
      recognition of antigen, they are activated and differentiate into effector and
      memory T cells. While effector T cells carry out the function of the immune
      response, memory T cells can last up to the life time of the individual, and are
      activated by subsequent antigenic exposure. Throughout this life cycle, the T
      cell uses the same receptor for antigen, the T cell Receptor, a complex multi
      subunit receptor. Recognition of antigen presented by peptide/MHC complexes on
      antigen presenting cells unleashes signaling pathways that control T cell
      activation at each stage. In this review, we discuss the signals regulated by the
      T cell receptor in naive and effector/memory T cells.

PMID- 22981633
TI  - Effect of S-allylcysteine, a sulphur containing amino acid on iron metabolism in
      streptozotocin induced diabetic rats.
AB  - It is suggested that iron may play a role in the pathogenesis of diabetes. Iron
      is not only chaperoned through its essential functional pathways, but it also
      causes damage to biological systems by catalyzing the production of reactive
      oxygen species. So, the parenchymal tissues of several organs are subject to cell
      injury and functional insufficiency due to excess deposition of iron. The present
      study investigated the effects of S-allylcysteine (SAC), a sulphur containing
      amino acid derived from garlic on the changes in iron metabolism induced by
      oxidative stress in tissues, as well as on serum biochemical parameters of
      streptozotocin (STZ)-induced diabetic rats. SAC was administered orally for
      45days to control and experimental diabetic rats. The effects of SAC on glucose,
      insulin, serum iron, ferritin, transferrin, serum bilirubin, heart heme oxygenase
      activity (HO) and delta-aminolevulinicacid dehydratase activity (delta-ALA-D) in
      liver and kidneys were studied. The levels of glucose, iron, ferritin, bilirubin
      and HO in liver were increased significantly (p<0.05) whereas the levels of
      insulin, transferrin and delta-ALA-D in tissues were decreased in diabetic rats.
      Administration of SAC to diabetic rats showed a decrease in blood glucose, iron,
      ferritin, bilirubin and HO. In addition, the levels of insulin, transferrin and
      delta-ALA-D activity in tissues were increased in SAC treated diabetic rats.
      These findings suggest that S-allylcysteine could have a protective effect
      against alterations in oxidative stress induced iron metabolism in the diabetic
      state which was evidenced by the capacity of this natural antioxidant to modulate
      parameters of iron metabolism.

PMID- 22981632
TI  - Cancer stem cells.
AB  - Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with
      capabilities of self-renewal, differentiation, and tumorigenicity when
      transplanted into an animal host. A number of cell surface markers such as CD44,
      CD24, and CD133 are often used to identify and enrich CSCs. A regulatory network
      consisting of microRNAs and Wnt/beta-catenin, Notch, and Hedgehog signaling
      pathways controls CSC properties. The clinical relevance of CSCs has been
      strengthened by emerging evidence, demonstrating that CSCs are resistant to
      conventional chemotherapy and radiation treatment and that CSCs are very likely
      to be the origin of cancer metastasis. CSCs are believed to be an important
      target for novel anti-cancer drug discovery. Herein we summarize the current
      understanding of CSCs, with a focus on the role of miRNA and epithelial
      mesenchymal transition (EMT), and discuss the clinical application of targeting
      CSCs for cancer treatment.

PMID- 22981634
TI  - Classification of herbal mixtures on the basis of some metals content using
      pattern recognition techniques.
AB  - The purpose of this study was to investigate the content of trace elements in
      relation to the composition of domestic herbal mixtures. Cluster analysis,
      principal components analysis, and self-organizing maps were applied to identify
      existing relationships. The concentrations of Ni, Pb, Cd, Cr, Cu, Fe, Mn, Zn in
      81 samples of herbal mixtures were determined with application of FAAS. The study
      showed that the levels of trace elements in some herbal mixtures of the same
      composition were comparable. The projection of herbal samples onto topological
      maps of adjustable sizes allowed recognition of the identical herbal preparations
      characterized by dissimilar levels of trace elements. The elements which played
      the most important role in recognition of the herbal samples were Mn, Ni, Zn and
      partly Cu, Fe and Cd.

PMID- 22981635
TI  - On-line preconcentration/determination of zinc from water, biological and food
      samples using synthesized chelating resin and flame atomic absorption
      spectrometry.
AB  - An on-line flow injection pre-concentration-flame atomic absorption spectrometry
      method was developed to determine trace zinc in water (tap, dam, and well water),
      biological (hair and nail), and liver samples. As a solid phase extractant, a
      synthesized new chelating resin, poly(2-thiozylmethacrylamide-co-divinylbenzene
      co-2-acrylamido-2-methyl-1-propane sulfonic acid) was used. The resin was
      characterized by Fourier transform infrared spectroscopy, elemental analysis, and
      surface area by nitrogen sorption. A pre-concentration factor of 40-fold for a
      sample volume of 12.6 mL was obtained by using the time-based technique. The
      detection limit for the pre-concentration method was found to be 2.2 MUg L(-1).
      The precision (as RSD,%) for 10 replicate determinations at the 0.04 MUg mL(-1)
      Zn concentration was 1.2%. The calibration graph using the pre-concentration
      system for zinc was linear with a correlation coefficient of 0.998 in the
      concentration range from 0.005 to 0.05 MUg mL(-1). The applicability and accuracy
      of the developed method were estimated by the analysis spiked water, biological,
      liver samples (83-105%), and also certified reference material TMDA-70 (fortified
      lake water) and SPS-WW1 Batch 111-Wastewater. The results were in agreement with
      the certified values.

PMID- 22981636
TI  - Neonatal vocal cord paralysis-an early presentation of hereditary neuralgic
      amyotrophy due to a mutation in the SEPT9 gene.
AB  - Hereditary neuralgic amyotrophy is a rare autosomal dominant disorder involving
      recurrent episodes of painful brachial plexus neuropathies. Involvement of other
      nerves has been described in some families. The age of onset is from infancy to
      adulthood. Mutations in the SEPT9 gene were identified in approximately half of
      the hereditary neuralgic amyotrophy families. We evaluated a family with six
      affected members from three generations with a point mutation in the SEPT9 gene.
      One of the patients presented in the neonatal period with vocal cord paralysis
      necessitating intubation and prolonged ventilation. The neonatal presentation of
      vocal cord paralysis broadens the phenotypic spectrum of hereditary neuralgic
      amyotrophy. The identification of a SEPT9 mutation in a neonate with respiratory
      distress due to vocal cord paralysis expands the differential diagnosis in these
      patients.

PMID- 22981638
TI  - Infectious risk of endovaginal and transrectal ultrasonography: systematic review
      and meta-analysis.
AB  - BACKGROUND: Appropriate endovaginal/rectal ultrasound transducer disinfection has
      been an ongoing and vexed question in gynaecology, obstetrics and urology.
      However, the routine use of probe covers followed by low-level disinfection
      (wipes/spray) is usually applied between patients in some countries (e.g.
      France). AIM: To perform a systematic review and meta-analysis of the scientific
      literature in order to identify case reports of contamination following
      endovaginal/rectal probe use, and to estimate the infection prevalence related to
      the use of these probes in common daily practice. METHODS: Systematic review and
      meta-analysis. RESULTS: From the 867 potentially eligible references, 32 articles
      were finally included. Very few cases with an established route of contamination
      had been reported. Indeed, apart from occurrence of outbreaks, it is difficult if
      not impossible to detect viral contamination through the use of
      endovaginal/rectal ultrasound probes. However, there was a pooled prevalence of
      12.9% (95% confidence interval: 1.7-24.3) for pathogenic bacteria, and 1.0% (0.0
      10.0) for frequently occurring virus (human papillomavirus, herpes simplex virus,
      and cytomegalovirus) for endovaginal/rectal probes, both after low-level
      disinfection. The pooled prevalence of infected patients after transrectal
      ultrasound and guided biopsies was estimated to be 3.1% (1.6-4.3). CONCLUSIONS:
      There appears to be a risk of transmitting bacterial or viral infections via
      endovaginal/rectal ultrasound transducer, and the present meta-analysis provides
      an estimate of this risk. Further research with sophisticated modelling is
      warranted to quantify the risk.

PMID- 22981637
TI  - Palm reversal errors in native-signing children with autism.
AB  - Children with autism spectrum disorder (ASD) who have native exposure to a sign
      language such as American Sign Language (ASL) have received almost no scientific
      attention. This paper reports the first studies on a sample of five native
      signing children (four deaf children of deaf parents and one hearing child of
      deaf parents; ages 4;6 to 7;5) diagnosed with ASD. A domain-general deficit in
      the ability of children with ASD to replicate the gestures of others is
      hypothesized to be a source of palm orientation reversal errors in sign. In Study
      1, naturalistic language samples were collected from three native-signing
      children with ASD and were analyzed for errors in handshape, location, movement
      and palm orientation. In Study 2, four native-signing children with ASD were
      compared to 12 typically developing deaf children (ages 3;7 to 6;9, all born to
      deaf parents) on a fingerspelling task. In both studies children with ASD showed
      a tendency to reverse palm orientation on signs specified for inward/outward
      orientation. Typically developing deaf children did not produce any such errors
      in palm orientation. We conclude that this kind of palm reversal has a perceptual
      rather than a motoric source, and is further evidence of a "self-other mapping"
      deficit in ASD.

PMID- 22981639
TI  - [The introduction of clinical guidelines: could their computerisation help us?].

PMID- 22981640
TI  - [High-dose daptomycin use in methicillin-resistant Staphylococcus aureus
      disseminated infection].
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
      infections are an increasing problem in our country. Daptomycin is a bactericidal
      antibiotic with activity against CA-MRSA. Experience using high-dose daptomycin
      is reviewed in three paediatric patients with severe-disseminated CA-MRSA
      infection with a favourable microbiological and clinical response.

PMID- 22981641
TI  - In vitro and in vivo pharmacological characterization of the main metabolites of
      nalfurafine hydrochloride.
AB  - Pharmacological characterization of the main metabolites of nalfurafine
      hydrochloride ((E)-N-[17-(cyclopropylmethyl)-4,5alpha-epoxy-3,14
      dihydroxymorphinan-6beta-yl]-3-(furan-3-yl)-N-methylprop-2-enamide
      monohydrochloride; a selective kappa-opioid receptor agonist and an antipruritic
      for uremic pruritus in hemodialysis patients in Japan) such as 17
      decyclopropylmethylated nalfurafine (de-CPM), 3-glucuronide of nalfurafine (NFA
      G) and 3-glucuronide of 17-decyclopropylmethylated nalfurafine (de-CPM-G) was
      performed in vitro (human opioid receptor radioligand binding assay and forskolin
      stimulated cyclic adenosine monophosphate (cAMP) assay) and in vivo (substance P
      induced scratching behavior in mice). These main metabolites of nalfurafine
      showed the low affinities for human kappa-, MU- and delta-opioid receptors except
      for the affinity of de-CPM to kappa-opioid receptor (inhibition constant (Ki)
      values: 5.95nmol/l), which was 24 times lower than that of nalfurafine. Moreover,
      the main metabolites of nalfurafine had much lower agonistic activities than that
      of nalfurafine for three opioid receptors in forskolin-stimulated cAMP assays. In
      the substance P-induced mouse scratching behavior, the subcutaneous
      administration of each metabolite did not statistically significantly reduce the
      scratching behavior at doses up to 1000MUg/kg which was 100 times higher than the
      effective dose of nalfurafine. These findings suggest that the main metabolites
      of nalfurafine do not make any contribution to its pharmacological actions
      including antipruritic effects in vivo.

PMID- 22981642
TI  - Spontaneous brachial pseudo-aneurysm in a 12-year-old with kyphoscoliosis-type
      Ehlers-Danlos Syndrome.
AB  - The Ehlers-Danlos Syndrome (EDS) is a rare connective tissue disorder
      characterised by fragility of the soft connective tissues and widespread
      manifestations in skin, ligaments, joints, blood vessels and internal organs. We
      report a case of a 12-year-old boy, previously diagnosed with kyphoscoliosis-type
      EDS (type VI), presenting with a left brachial artery pseudo-aneursym with
      history of multiple spontaneous and post-traumatic arterial ruptures. Surgical
      management of this patient was performed successfully by primary repair of
      brachial artery lesion.

PMID- 22981643
TI  - Classification of complications after progressive long bone lengthening: proposal
      for a new classification.
AB  - INTRODUCTION: Long bone lengthening surgery using progressive surgical methods
      has been the source of frequent complications. Some authors have classified these
      complications either descriptively, according to the date of onset after the
      operation, or based on their severity. The Caton classification (1985) has had
      the virtue of contributing the notion of the treatment contract stipulating the
      objective to reach in treatment. Within the context of the preoperative
      information delivered to patients and their family, this contract can be improved
      by adding a notion of maximum treatment duration. The objective of this study was
      therefore to propose a classification that includes honoring a triple contract
      associating the planned gain in bone length, the duration of treatment, and the
      occurrence of sequelae. MATERIALS AND METHODS: The classification of
      complications proposed includes four grades: grade I: triple contract honored,
      including a few treatments without general anesthesia; grade II: triple contract
      fulfilled, but with unplanned interventions under general anesthesia; grade III:
      the time stipulated was not honored because the time to obtain bone union was too
      long or because the program was interrupted; grade IV: sequelae are present. This
      classification was assessed based on a consecutive series of 34 surgical
      procedures in 32 patients (two patients underwent two lengthening procedures
      during this period) at 43 bone segments associating progressive lengthening with
      external fixation or with nail lengthening. The grade of each complication was
      determined by each of the authors according to the classification proposed and
      other classifications reported in the literature (Caton, Paley, Popkov, and
      Donnan). RESULTS: Approximately one-third (10) of the 34 lengthening procedures
      did not present any complications. Two-thirds (24) presented 30 complications.
      Consensus was obtained between all the authors on the grades proposed for our
      classification and the Caton classification, but consensus was not reached with
      the other classifications in which part of the interpretation was subjective
      (Paley, Popkov, and Donnan). DISCUSSION: The classification proposed required
      respecting predetermined objectives during limb lengthening surgery based on a
      triple contract: gain, duration, and function. It is reliable and reproducible by
      different operators because the criteria are objective. It can also be applied to
      diverse surgical techniques, whether with external fixation and/or internal
      osteosynthesis. LEVEL OF EVIDENCE: Level IV: retrospective study or historical
      series.

PMID- 22981644
TI  - Osteoid osteoma transformation into osteoblastoma: fact or fiction?
AB  - BACKGROUND: Osteoid osteoma and osteoblastoma are rare, benign, bone-forming
      tumours. The clinical presentation, imaging study findings, and course indicate
      clearly that these two tumours are distinct entities. CLINICAL REPORTS: We report
      two cases suggesting transformation of osteoid osteoma into osteoblastoma and
      therefore inviting a discussion of the links between these two tumours. An 11
      year-old girl with a small metaphyseal lesion of the proximal tibia was given a
      diagnosis of osteoid osteoma. Over the next few weeks, worsening pain and marked
      tumour growth prompted a biopsy, which was consistent with an aggressive
      osteoblastoma. A review of the case suggested primary osteoblastoma at the
      earliest stage of development. In a 14-year-old boy, en-bloc excision was
      performed to remove a 1cm defect located within the femoral shaft cortex and
      typical for osteoid osteoma. An asymptomatic recurrence measuring 20mm along the
      long axis was removed 18 months later. Reassessment of the histological slides
      indicated recurrence of an incompletely excised osteoid osteoma. DISCUSSION: The
      histological similarities between osteoid osteoma and osteoblastoma, together
      with the lesion size criterion, may result in confusion. Collaboration between
      the clinician and pathologist is crucial and should take the tempo of evolution
      into account. CONCLUSION: The histopathological differences between these two
      tumour types deserve to be emphasized. The data reported here challenge the
      concept that osteoid osteoma can transform into osteoblastoma. These two tumours
      are distinct entities that should no longer be differentiated based on size, as
      was long done in the past.

PMID- 22981645
TI  - Addressing critical issues in the development of an Oncology Information System.
AB  - PURPOSES: This paper presents the experience on the design and implementation of
      a user-centered Oncology Information System developed for the Medical Oncology
      Department at the "Hospital Universitario Virgen de la Victoria", in Malaga,
      Spain. The project focused on the aspects considered in the literature as
      critical factors for a successful deployment and usage of a health information
      system. METHODS: System usability, adequate technology, integration of clinical
      routines, real-time statistical analysis of data, information confidentiality and
      standard protocol-based external interconnection were the key aspects considered.
      RESULTS: The developed system is based on a web application with a modular and
      layered architecture accounting for usability, ease of maintenance and further
      system development. Evaluation of system usability was carried at three and
      fifteen months after system deployment to analyze the advantages/disadvantages
      experienced by the end-users. CONCLUSIONS: A thorough prior analysis of clinical
      activities and workflows, the use of the adequate technology, and the
      availability of data analysis tools will almost guarantee success in the
      deployment of an Oncology Information System.

PMID- 22981646
TI  - Measurement of meat color using a computer vision system.
AB  - The limits of the colorimeter and a technique of image analysis in evaluating the
      color of beef, pork, and chicken were investigated. The Minolta CR-400
      colorimeter and a computer vision system (CVS) were employed to measure
      colorimetric characteristics. To evaluate the chromatic fidelity of the image of
      the sample displayed on the monitor, a similarity test was carried out using a
      trained panel. The panelists found the digital images of the samples visualized
      on the monitor very similar to the actual ones (P<0.001). During the first
      similarity test the panelists observed at the same time both the actual meat
      sample and the sample image on the monitor in order to evaluate the similarity
      between them (test A). Moreover, the panelists were asked to evaluate the
      similarity between two colors, both generated by the software Adobe Photoshop CS3
      one using the L, a and b values read by the colorimeter and the other obtained
      using the CVS (test B); which of the two colors was more similar to the sample
      visualized on the monitor was also assessed (test C). The panelists found the
      digital images very similar to the actual samples (P<0.001). As to the similarity
      (test B) between the CVS- and colorimeter-based colors the panelists found
      significant differences between them (P<0.001). Test C showed that the color of
      the sample on the monitor was more similar to the CVS generated color than to the
      colorimeter generated color. The differences between the values of the L, a, b,
      hue angle and chroma obtained with the CVS and the colorimeter were statistically
      significant (P<0.05-0.001). These results showed that the colorimeter did not
      generate coordinates corresponding to the true color of meat. Instead, the CVS
      method seemed to give valid measurements that reproduced a color very similar to
      the real one.

PMID- 22981647
TI  - Natural deletion of L35Y36 in p6 gag eliminate LYPXnL/ALIX auxiliary virus
      release pathway in HIV-1 subtype C.
AB  - Natural loss of L35Y36 residues in ALIX binding site of HIV-1 subtype C was found
      to prevent the p6 gag-ALIX interaction. Over expression of ALIX 364-716 (V
      domain) unlike pNL4.3 (subtype B), also did not inhibit the release of chimeric
      pNL4.3 expressing subtype C p6 late domain. Loss of V domain binding consequently
      affected the ALIX mediated particle release in the absence of PTAP/TSG101
      pathway. Our data indicated absence of LYPXnL/ALIX pathway in HIV-1 subtype C.

PMID- 22981648
TI  - Imidazo-benzothiazoles a potent microRNA modulator involved in cell
      proliferation.
AB  - MicroRNAs are endogenously expressed tiny non-coding RNAs that control gene
      expression at the post-transcriptional level and regulate processes of cell
      growth, differentiation, proliferation and apoptosis. Aberrant expression of
      microRNAs correlates with various cancers. Our experiments demonstrated that
      imidazo-benzothiazole conjugates caused apoptosis in colon cancer cells by
      modulating the expression of microRNAs. In vivo study in Drosophila melanogaster
      has exhibited inhibitory action on bantam microRNA, the homolog of human miR-542
      5p that is involved in deciding the cellular cues that regulate the balance
      between proliferation and apoptosis. The expression of direct targets of bantam
      such as Hid and HDAC-6 were affected upon compound treatment. Interestingly,
      these conjugates downregulate the genes involved in microRNA biogenesis such as
      Drosha, Pasha and Dicer-1. Our findings have elucidated the microRNA inhibitory
      role of imidazo-benzothiazole conjugates.

PMID- 22981649
TI  - Oxytocin and vasopressin in rodent behaviors related to social dysfunctions in
      autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) and social anxiety disorder involve various forms
      of social deficits like impaired affiliative behavior, social cognition and
      social approach. Although the neurobiological underpinnings of these disorders
      are largely unknown, rodent and human studies suggest an involvement of the
      evolutionary highly conserved oxytocin (OXT) and vasopressin (AVP), as these
      neuropeptides modulate various aspects of mammalian social behaviors. In this
      review we summarize the current knowledge regarding the involvement of brain OXT
      and AVP in rodent social behaviors related to social dysfunctions in ASD.
      Starting with an introduction into the neurobiology of the central OXT and AVP
      systems (neuroanatomy, central release, receptor distribution) we describe the
      distinct roles OXT and AVP play in basic social behaviors in rodents, i.e.
      affiliative behavior (pair-bonding and maternal behavior), social cognition
      (social memory), and social approach (social preference or social avoidance). The
      regulatory capacity of OXT and AVP to modulate social behaviors in various rodent
      species implies a high translational potential, in particular that dys
      regulations in the brain neuropeptide systems may underlie social dysfunctions in
      ASD. It also suggests that the brain OXT and AVP systems are promising
      pharmacotherapeutic targets to improve social behaviors and to reverse social
      deficits. 

PMID- 22981650
TI  - Left auditory cortex dysfunction in hallucinating patients with schizophrenia: an
      MEG study.

PMID- 22981651
TI  - Multiple mechanisms for distal axonal loss in Guillain-Barre syndrome.

PMID- 22981652
TI  - Anterior pituitary cell networks.
AB  - Both endocrine and non-endocrine cells of the pituitary gland are organized into
      structural and functional networks which are formed during embryonic development
      but which may be modified throughout life. Structural mapping of the various
      endocrine cell types has highlighted the existence of distinct network motifs and
      relationships with the vasculature which may relate to temporal differences in
      their output. Functional characterization of the network activity of growth
      hormone and prolactin cells has revealed a role for cell organization in gene
      regulation, the plasticity of pituitary hormone output and remarkably the ability
      to memorize altered demand. As such, the description of these endocrine cell
      networks alters the concept of the pituitary from a gland which simply responds
      to external regulation to that of an oscillator which may memorize information
      and constantly adapt its coordinated networks' responses to the flow of
      hypothalamic inputs.

PMID- 22981654
TI  - Estrogens facilitate memory processing through membrane mediated mechanisms and
      alterations in spine density.
AB  - Estrogens exert sustained, genomically mediated effects on memory throughout the
      female life cycle, but here we review new studies documenting rapid effects of
      estradiol on memory, which are exerted through membrane-mediated mechanisms. Use
      of recognition memory tasks in rats shows that estrogens enhance memory
      consolidation within 1h. 17alpha-Estradiol is more potent than 17beta-estradiol,
      and the dose response relationship between estrogens and memory is an inverted U
      shape. Use of specific estrogen receptor (ER) agonists suggests mediation by an
      ERbeta-like membrane receptor. Enhanced memory is associated with increased spine
      density and altered noradrenergic activity in the medial prefrontal cortex and
      hippocampus within 30 min of administration. The environmental chemical,
      bisphenol-A, rapidly antagonizes enhancements in memory in both sexes possibly
      through actions on spines. Thus, estradiol and related compounds exert rapid
      alterations in cognition through non-genomic mechanisms, a finding which may
      provide a basis for better understanding and treating memory impairments.

PMID- 22981655
TI  - Cholinergic blockade frees fear extinction from its contextual dependency.
AB  - BACKGROUND: Fears that are maladaptive or inappropriate can be reduced through
      extinction training. However, extinction is highly context-sensitive, resulting
      in the renewal of fear after shifts in context and limiting the clinical efficacy
      of extinction training. Lesion and inactivation studies have shown that the
      contextualization of extinction depends on the hippocampus. Parallel studies have
      found that intrahippocampal scopolamine (Scop) blocks contextual fear
      conditioning. Importantly, this effect was replicated with a noninvasive
      technique in which a low dose of Scop was administered systemically. We aimed to
      transfer the effects of this noninvasive approach to block the contextualization
      of fear extinction. METHODS: Rats were tone fear conditioned and extinguished
      under various systemic doses of Scop or the saline vehicle. They were
      subsequently tested (off drug) for tone fear in a context that was the same
      (control subjects) or shifted (renewal group) with respect to the extinction
      context. RESULTS: The lowest dose of Scop produced a significant attenuation of
      fear renewal when renewal was tested either in the original training context or a
      novel context. The drug also slowed the rate of long-term extinction memory
      formation, which was readily overcome by extending extinction training.
      Scopolamine only gave this effect when it was administered during but not after
      extinction training. Higher doses of Scop severely disrupted extinction learning.
      CONCLUSIONS: We discovered that disrupting contextual processing during
      extinction with the cholinergic antagonist Scop blocked subsequent fear renewal.
      Low doses of Scop might be a clinically promising adjunct to exposure therapy by
      making extinction more relapse-resistant.

PMID- 22981656
TI  - Prefrontal cortex modulates desire and dread generated by nucleus accumbens
      glutamate disruption.
AB  - BACKGROUND: Corticolimbic circuits, including direct projections from prefrontal
      cortex to nucleus accumbens (NAc), permit top-down control of intense motivations
      generated by subcortical circuits. In rats, localized disruptions of glutamate
      signaling within medial shell of NAc generate desire or dread, anatomically
      organized along a rostrocaudal gradient analogous to a limbic keyboard. At
      rostral locations in shell, these disruptions generate appetitive eating, but at
      caudal locations the disruptions generate progressively fearful behaviors
      (distress vocalizations, escape attempts, and antipredator reactions). Here, we
      asked whether medial prefrontal cortex can modulate intense motivations generated
      by subcortical NAc disruptions. METHODS: We used simultaneous microinjections in
      medial prefrontal cortex regions and in NAc shell to examine whether the desire
      or dread generated by NAc shell disruptions is modulated by activation/inhibition
      of three specific regions of prefrontal cortex: medial orbitofrontal cortex,
      infralimbic cortex (homologous to area 25 or subgenual anterior cingulate in the
      human), or prelimbic cortex (midventral anterior cingulate). RESULTS: We found
      that activation of medial orbitofrontal cortex biased intense bivalent motivation
      in an appetitive direction by amplifying generation of eating behavior by middle
      to caudal NAc disruptions, without altering fear. In contrast, activation of
      infralimbic prefrontal cortex powerfully and generally suppressed both appetitive
      eating and fearful behaviors generated by NAc shell disruptions. CONCLUSIONS:
      These results suggest that corticolimbic projections from discrete prefrontal
      regions can either bias motivational valence or generally suppress subcortically
      generated intense motivations of desire or fear.

PMID- 22981657
TI  - Magnetic transfer contrast accurately localizes substantia nigra confirmed by
      histology.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has multiple contrast mechanisms.
      Like various staining techniques in histology, each contrast type reveals
      different information about the structure of the brain. However, it is not always
      clear how structures visible in MRI correspond to structures previously
      identified by histology. The purpose of this study was to determine if magnetic
      transfer contrast (MTC) or T2 contrast MRI was better at delineating the
      substantia nigra (SN). METHODS: MRI scans were acquired in vivo from two nonhuman
      primates (NHPs). The NHPs were subsequently euthanized, perfused, and their
      brains sectioned for histologic analyses. Each slice was photographed before
      sectioning. Each brain was sectioned into approximately 500 sections, 40 MUm
      each, encompassing most of the cortex, midbrain, and dorsal parts of the
      hindbrain. Levels corresponding to anatomic MRI images were selected. From these,
      adjacent sections were stained using Kluver-Barrera (myelin and cell bodies) or
      tyrosine hydroxylase (dopaminergic neurons) immunohistochemistry. The resulting
      images were coregistered to the block-face images using a moving least squares
      algorithm with similarity transformations. MR images were similarly coregistered
      to the block-face images, allowing the structures on MRI to be identified with
      structures on the histologic images. RESULTS: We found that hyperintense (light)
      areas in MTC images were coextensive with the SN as delineated histologically.
      The hypointense (dark) areas in T2-weighted images were not coextensive with the
      SN but extended partially into the SN and partially into the cerebral peduncles.
      CONCLUSIONS: MTC is more accurate than T2-weighting for localizing the SN in
      vivo.

PMID- 22981658
TI  - A case of near-fatal flecainide overdose in a neonate successfully treated with
      sodium bicarbonate.
AB  - BACKGROUND: Flecainide is a class IC antidysrhythmic primarily indicated for
      ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC
      antidysrhythmic overdose has a reported mortality of 22%, and death results from
      dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide
      overdose in an 18-day-old treated successfully with sodium bicarbonate. CASE
      REPORT: An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high
      heart rates (220-240 beats/min) and electrocardiographic changes consistent with
      SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a
      transthoracic echocardiogram showed no underlying structural abnormality. The
      patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the
      fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40
      beats/min with no palpable pulse. The patient was given 0.1 mg of atropine
      intravenously, with an increase of the heart rate to 160 beats/min. The child's
      cardiac monitor revealed a wide-complex tachycardia with left bundle branch
      morphology, with associated pallor and poor capillary refill. Sodium bicarbonate
      was administered intravenously due to suspected flecainide toxicity.
      Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium
      bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum
      flecainide concentration was 1360 MUg/L (therapeutic, 200-1000 MUg/L) drawn 1 h
      before the cardiac arrest. It was later discovered that a twofold dosing error
      occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses.
      CONCLUSION: Flecainide toxicity in children is rare, especially in neonates. It
      is important for clinicians to be able to identify and treat this uncommon
      poisoning.

PMID- 22981659
TI  - Applying the Boston syncope criteria to near syncope.
AB  - BACKGROUND: We recently demonstrated that near-syncope patients are as likely as
      syncope patients to experience adverse outcomes. The Boston Syncope Criteria
      (BSC) identify patients with syncope unlikely to have adverse outcomes and reduce
      hospitalizations. It is unclear whether these guidelines could reduce
      hospitalization in near syncope as well. OBJECTIVE: To determine if BSC
      accurately predict which near-syncope patients require hospitalization. METHODS:
      A prospective observational study enrolled from August 2007 to October 2008
      consecutive emergency department (ED) patients (aged > 18 years) with near
      syncope. BSC were first employed assuming that any patient with risk factors for
      adverse outcomes should be admitted, and then utilized using a modified rule: if
      the etiology of near syncope is dehydration or vasovagal, and ED work-up is
      normal, patients may be discharged even with risk factors. Outcomes were
      identified by chart review and 30-day follow-up calls. RESULTS: Of 244 patients
      with near syncope, 111 were admitted, with 49 adverse outcomes. No adverse
      outcomes occurred among discharged patients. If BSC had been followed strictly,
      another 41 patients with risk factors would have been admitted and 34 discharged,
      a 3% increase in admission rate. However, using the modified criteria, only 68
      patients would have required admission, a 38% reduction in admission, with no
      missed adverse outcomes on follow-up. CONCLUSION: Although near-syncope patients
      may have risk factors for adverse outcomes similar to those with syncope, if the
      etiology of near syncope is dehydration or vasovagal, and ED work-up is normal,
      these patients may be discharged even with risk factors.

PMID- 22981660
TI  - Painful ophthalmoplegia of the right eye in a 20-year-old man.
AB  - BACKGROUND: Painful ophthalmoplegia is an infrequent but very important
      presentation in the acute care setting and requires a thorough neurologic
      evaluation to determine its cause. This clinical sign has a large differential
      and generally indicates a serious cerebrovascular process. CASE REPORT: We
      describe a patient with a subacute presentation of painful ophthalmoplegia,
      ultimately diagnosed as Tolosa-Hunt syndrome, a rare inflammatory process of the
      cavernous sinus. CONCLUSION: This case highlights the importance for the
      Emergency Physician to quickly recognize painful ophthalmoplegia and rapidly
      elucidate the cause to prevent further complications for the patient.

PMID- 22981653
TI  - Estradiol signaling in the regulation of reproduction and energy balance.
AB  - Our knowledge of membrane estrogenic signaling mechanisms and their interactions
      that regulate physiology and behavior has grown rapidly over the past three
      decades. The discovery of novel membrane estrogen receptors and their signaling
      mechanisms has started to reveal the complex timing and interactions of these
      various signaling mechanisms with classical genomic steroid actions within the
      nervous system to regulate physiology and behavior. The activation of the various
      estrogenic signaling mechanisms is site specific and differs across the estrous
      cycle acting through both classical genomic mechanisms and rapid membrane
      initiated signaling to coordinate reproductive behavior and physiology. This
      review focuses on our current understanding of estrogenic signaling mechanisms to
      promote: (1) sexual receptivity within the arcuate nucleus of the hypothalamus,
      (2) estrogen positive feedback that stimulates de novo neuroprogesterone
      synthesis to trigger the luteinizing hormone surge important for ovulation and
      estrous cyclicity, and (3) alterations in energy balance.

PMID- 22981661
TI  - Predicting peripheral venous access difficulty in the emergency department using
      body mass index and a clinical evaluation of venous accessibility.
AB  - BACKGROUND: Peripheral venous (PV) cannulation, one of the most common technical
      procedures in Emergency Medicine, may prove challenging, even to experienced
      Emergency Department (ED) staff. Morbid obesity (body mass index [BMI] >= 40) has
      been reported as a risk factor for PV access failure in the operating room.
      OBJECTIVES: We investigated PV access difficulty in the ED, across BMI
      categories, focusing on patient-related predicting factors. METHODS: Prospective,
      observational study including adult patients requiring PV lines. Operators were
      skilled nurses and physicians. PV accessibility was clinically evaluated before
      all cannulation attempts, using vein visibility and palpability. Patient and PV
      placement characteristics were recorded. Primary outcome was failure at first
      attempt. Outcome frequency and comparisons between groups were examined.
      Predictors of difficult cannulation were explored using logistic regression. A p
      value <0.05 was considered significant. RESULTS: PV lines were placed in 563
      consecutive patients (53 +/- 23 years, BMI: 26 +/- 7 kg/m(2)), with a success
      rate of 98.6%, and a mean attempt of 1.3 +/- 0.7 (range 1-7). Failure at the
      first attempt was recorded in 21% of patients (95% confidence interval [CI] 17.6
      24.4). Independent risk factors were: a BMI >= 30 (odds ratio [OR] 1.98, 95% CI
      1.09-3.60), a BMI < 18.5 (OR 2.24; 95% CI 1.07-4.66), an unfavorable (OR 1.66,
      95% CI 1.02-2.69), and very unfavorable clinical assessment of PV accessibility
      (OR 2.38, 95% CI 1.15-4.93). CONCLUSION: Obesity, underweight, an unfavorable,
      and a very unfavorable clinical evaluation of PV accessibility are independent
      risk factors for difficult PV access. Early recognition of patients at risk could
      help in planning alternative approaches for achieving rapid PV access.

PMID- 22981662
TI  - Ultrasound diagnosis of traumatic lens dislocation.

PMID- 22981663
TI  - Foot compartment syndrome: a rare presentation to the Emergency Department.
AB  - BACKGROUND: Compartment syndrome of the foot is a rare but life- and limb
      threatening condition that is often difficult to diagnose. The common signs and
      symptoms of compartment syndrome are pain out of proportion to the injury, pain
      with passive stretch of the compartment, paresis, paresthesias, and often, intact
      pulses. Foot compartment syndrome is often caused by traumatic injuries, and the
      clinical presentation may be confusing in this setting. The foot contains nine
      compartments, which should all be assessed for elevated compartment pressures.
      Definitive management is fasciotomy. Prompt recognition, diagnosis, and treatment
      are essential to prevent devastating complications. OBJECTIVES: This article
      discusses the key components of presentation, diagnosis, and management of foot
      compartment syndrome. CASE REPORT: A patient presented to the Emergency
      Department (ED) with a crush injury of his foot. He had significant swelling and
      pain in his foot, but no fractures were identified on X-ray study. Given the
      severity of his injury and pain, foot compartment pressures were measured to
      accurately diagnose foot compartment syndrome. The patient underwent fasciotomies
      of the foot within 3 h of presentation to the ED and suffered no sequelae at the
      time of follow-up in clinic. CONCLUSION: Foot compartment syndrome is a surgical
      emergency that can be difficult to diagnose. Early diagnosis with compartment
      pressure measurements is crucial, as definitive management with fasciotomies can
      prevent long-term sequelae.

PMID- 22981664
TI  - The effect of nimodipine on memory impairment during spontaneous morphine
      withdrawal in mice: Corticosterone interaction.
AB  - Effects of the nimodipine, L-type calcium channel antagonist, has been studied on
      memory loss caused by spontaneous morphine withdrawal in mice. Mice were made
      dependent by increasing doses of morphine over three days. Memory was evaluated
      using object recognition task, which is based on tendency of rodents to
      exploration of new objects. The test was comprised of three sections: 15 min
      habitation, 12 min first trial and 5 min test trial. Recognition index was
      evaluated 4h after the last dose of morphine. Nimodipine was administrated either
      in chronic form (1, 5 and 10mg/kg) with daily doses of morphine or it was given
      as a single injection (5 and 10mg/kg) on the last day. Nimodipine in both
      treatment forms prevented the memory impairment following spontaneous morphine
      withdrawal. Corticosterone concentration was increased in brain and blood of mice
      during abstinence phase and pretreatment with nimodipine prevented the increase
      in brain and blood corticosterone concentration. The results show that blockade
      of L-type calcium channels improves memory deficits caused by morphine
      withdrawal. This indicates that some kind of treatments, such as nimodipine,
      administrated over the acute withdrawal phase, can prevent memory deficit during
      withdrawal.

PMID- 22981665
TI  - The vascular-disrupting agent, combretastatin-A4-phosphate, enhances neurogenic
      vasoconstriction in rat small arteries.
AB  - Combretastatin-A4-phosphate (CA4P/CA4), an anti-cancer drug, induces tumour
      hypoxia by destabilizing the cytoskeleton in tumour endothelial cells.
      Hypertensive side effects have been observed. We hypothesized that CA4P/CA4 lead
      to endothelial dysfunction followed by increased vasoconstriction. Mesenteric
      small arteries and femoral arteries isolated from male Wistar rats were mounted
      in microvascular myographs for isometric tension recordings and electrical field
      stimulation (EFS). Immunoblotting of endothelial nitric oxide synthase (eNOS) was
      performed on human umbilical vein endothelial cells (HUVECs). CA4P failed per se
      to change vascular tone. In femoral arteries, endothelial cell removal, l-nitro
      arginine (l-NNA, an inhibitor of eNOS) and CA4P enhanced phenylephrine-induced
      vasoconstriction, while in mesenteric arteries only l-NNA leftward shifted
      concentration-response curves for phenylephrine. CA4P enhanced vasoconstriction
      induced by low frequency (0.5-4Hz) EFS in femoral arteries, but not in mesenteric
      arteries. Neurogenic contractions were inhibited by prazosin, an alpha(1)
      adrenoceptor antagonist. In mesenteric arteries, CA4P and l-NNA inhibited
      vasorelaxation induced by vanadate, a tyrosine phosphatase inhibitor. CA4P did
      not affect acetylcholine-induced relaxation. In HUVECs, CA4P increased
      phosphorylation at eNOS-Thr(495), a negative regulatory site, while the positive
      phosphorylation site eNOS-Ser(1177) was not affected. CA4 neither influenced the
      actions of phenylephrine, vanadate nor acetylcholine in femoral and mesenteric
      arteries. In conclusion, our findings suggest that CA4P, but not CA4, enhances
      sympathetic adrenergic vasoconstriction probably by increasing eNOS-Thr(495)
      phosphorylation, in a tissue selective manner. These findings encourage further
      investigation to show that the hypertension and regional organ ischemia induced
      by CA4P can be avoided by concomitant treatment with an alpha(1)-adrenoceptor
      antagonist.

PMID- 22981666
TI  - Escitalopram improves memory deficits induced by maternal separation in the rat.
AB  - Maternal separation (MS) induces depressive-like behavior and long-term changes
      in cognition in rats. Escitalopram is an antidepressant drug shown to reverse the
      depressive-like features caused by this stress model. However, it is not known if
      it can ameliorate the affected cognition. We now characterized the effect of
      escitalopram on hippocampal-dependent memory in rats submitted to the MS
      protocol. Male Wistar rats were assigned either to control (CTR) or maternal
      separated (MS) group. MS were separated from their dams between 2-14 postnatal
      days (PND) for 180min daily. Escitalopram was given in food pellets (0.34g/kg/day
      first 2 weeks and 0.41g/kg/day the subsequent period, average dose 25mg/kg) from
      PND 43 onwards, during 1 month. Depressive behavior was assessed in the forced
      swimming test (FST), and memory performance in the Morris water maze (MWM).
      Escitalopram significantly improved the FST's latency to despair in the MS group
      (n=6), but did not change the immobility time. All groups showed a significant
      learning effect in the MWM over time, but no differences have been found upon
      treatment (n=6). However, escitalopram treatment significantly increased the time
      spent on the platform quadrant in the probe trial in the MS group. We report here
      that chronic treatment with escitalopram is able to improve hippocampal dependent
      memory in a chronic stress model, while not changing the learning ability.
      Moreover, this is accompanied by an amelioration of the depressive like behavior.
      These results support the use of escitalopram to tackle underlying cognitive
      deficits caused by stress in early-life.

PMID- 22981667
TI  - Oral delivery of anticancer drugs III: formulation using drug delivery systems.
AB  - In the past few years, the growth of nanometric size drug delivery systems (DDS)
      has burst into challenging innovations enabling real progresses to achieve oral
      delivery of anticancer drugs. DDS, such as polymeric nanoparticles, micelles,
      dendrimers and lipid-based formulations enable physico-chemical properties of
      cytotoxic agents to be improved and oral bioavailability to be enhanced. In this
      review we highlight current DDS used for the oral delivery of anticancer drugs.

PMID- 22981668
TI  - Orphan drugs: the regulatory environment.
AB  - The definition of a rare disease is not universal and depends on the legislation
      and policies adopted by each region or country. The main objective of this
      article is to describe and discuss the legal framework and the regulatory
      environment of orphan drugs worldwide. Some reflections and discussions on the
      need for specific orphan drug legislation or policies are described at length.
      Furthermore, some aspects of the history of each region in respect of the orphan
      drug legislation evolution are outlined. This article describes and compares the
      orphan drug legislation or policies of the following countries or regions: United
      Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan
      and Canada. The incentives described in the orphan drug legislations or policies,
      the criteria for designation of orphan status and the authorisation process of an
      orphan drug are also described and compared. The legislations and policies are to
      some extent similar but not the same. It is important to understand the main
      differences among all available legislative systems to improve the international
      collaboration in the field of orphan drugs and rare diseases.

PMID- 22981669
TI  - Strabismus surgery in a patient with a Boston K-pro keratoprosthesis.
AB  - We report the case of a 33-year-old woman with sensory exotropia who developed
      diplopia following implantation of a Boston K-pro keratoprosthesis. She underwent
      uneventful, successful strabismus surgery with recovery of stereopsis. To the
      best of our knowledge, surgical treatment of diplopia related to sensory
      exotropia in a K-pro patient has not been previously reported.

PMID- 22981670
TI  - Fundoplication and the pediatric surgeon: implications for shared decision-making
      and the medical home.
AB  - OBJECTIVE: Almost one-half of all pediatric gastrostomy tube insertions are
      accompanied by a fundoplication, yet little is understood about the surgical
      decision-making for these procedures. The objective of this study was to examine
      the decision-making process of surgeons about whether to perform a fundoplication
      in children already scheduled to have a gastrostomy tube placed. METHODS: A
      written questionnaire of all pediatric surgeons at a major children's hospital
      was completed for each planned gastrostomy procedure over the course of 1 year;
      the questionnaire asked about various influences on the fundoplication decision:
      primary care and subspecialty physicians' opinions, patient characteristics, and
      parent opinions. Patient demographics and clinical characteristics from the
      medical record, as well as questionnaire responses, were summarized for each
      gastrostomy occurrence. We modeled the association of questionnaire responses and
      patient characteristics with the outcome of having a fundoplication. RESULTS: We
      received questionnaires on 161 of 169 eligible patients (95%). A total of 52% of
      patients had fundoplication. Primary care physicians were involved in 44% of
      decisions, and when involved had "a lot" of influence on the fundoplication
      decision only 28% of time, compared with neonatologists (61%), hospitalists
      (44%), pediatric pulmonologists (42%), and pediatric gastroenterologists (40%). A
      total of 86% of patients had a subspecialist involved, and 28% had >1
      subspecialist. A pH probe was performed in 7.5% of cases, and failed
      pharmacotherapy was noted by the surgeons in only 26.5% of the fundoplications
      performed. CONCLUSIONS: The decision to do a fundoplication was rarely based on
      definitive testing or failed medical treatment. From the surgeon's perspective,
      subspecialists were more influential than primary care physicians, which is at
      odds with current concepts of the medical home.

PMID- 22981671
TI  - Serum levels of glutathione peroxidase 3 in overweight and obese subjects from
      central Mexico.
AB  - BACKGROUND AND AIMS: Overweight and obesity are considered complex entities in
      which there are alterations in the concentration of antioxidant enzymes. It has
      been reported that glutathione peroxidase 3 (GPx3), an extracellular enzyme
      involved in the reduction of both hydro- and lipoperoxides, shows changes both in
      gene expression and protein concentration in animal models for type 2 diabetes
      (T2D) and obesity, but the variability of GPx3 levels in different human
      populations and under different health conditions are currently unclear. We
      undertook this study to determine the GPx3 levels in overweight and obese
      subjects from central Mexico. METHODS: Biochemical profile (serum glucose,
      insulin and lipid profile) and GPx3 concentrations were determined in 28 healthy
      subjects (control) and 133 subjects who were overweight or obese (OW-OB).
      RESULTS: The OW-OB group had a higher concentration of triacylglycerides (TAG)
      compared with the control group (201.2 +/- 88.7 vs. 100.3 +/- 46.4 mg/dL, p
      <0.05) and the TAG/high density lipoprotein-cholesterol (HDL-C) index (5.6 +/-
      2.8 vs. 2.1 +/- 1.2, p <0.05), whereas the concentration of HDL-C decreased (38.2
      +/- 8.7 vs. 50.1 +/- 14.5 mg/dL, p <0.05). Serum GPx3 was significantly higher in
      the OW-OB group than in the control group (175.4 +/- 25.4 vs. 143.5 +/- 23.1
      ng/dL). GPx3 concentration correlated with insulin sensitivity (IS) and the
      TAG/HDL-C index (Rho = -0.2336 and Rho = 0.2275) (p <0.01). CONCLUSIONS: The
      TAG/HDL-C index and serum GPx3 concentration increased in the OW-OB group. In
      addition, GPx3 had a significant correlation with IS, weight, and the TAG/HDL-C
      index.

PMID- 22981672
TI  - ICUD-EAU International Consultation on Bladder Cancer 2012: Non-muscle-invasive
      urothelial carcinoma of the bladder.
AB  - CONTEXT: Our aim was to present a summary of the Second International
      Consultation on Bladder Cancer recommendations on the diagnosis and treatment
      options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an
      evidence-based approach. OBJECTIVE: To critically review the recent data on the
      management of NMIBC to arrive at a general consensus. EVIDENCE ACQUISITION: A
      detailed Medline analysis was performed for original articles addressing the
      treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy,
      and follow-up. Proceedings from the last 5 yr of major conferences were also
      searched. EVIDENCE SYNTHESIS: The major findings are presented in an evidence
      based fashion. We analyzed large retrospective and prospective studies.
      CONCLUSIONS: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in
      situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly
      demanding challenges to urologic care. On the one hand, the high recurrence rate
      and low progression rate with Ta low-grade demand risk-adapted treatment and
      surveillance to provide thorough care while minimizing treatment-related burden.
      On the other hand, the propensity of Ta high-grade, T1, and CIS to progress
      demands intense care and timely consideration of radical cystectomy.

PMID- 22981673
TI  - Costs of radical prostatectomy for prostate cancer: a systematic review.
AB  - CONTEXT: Robot-assisted laparoscopic radical prostatectomy (RALP) has been
      rapidly adopted as a new approach for radical prostatectomy (RP) in patients with
      prostate cancer (PCa). The use of new technology may increase costs for RP.
      OBJECTIVE: To summarize data on direct costs of various approaches to RP and to
      discuss the consequences of cost differences. EVIDENCE ACQUISITION: A systematic
      literature search was performed in March 2012 using the PubMed, Web of Science,
      and Cochrane Library databases. A complex search strategy was applied. Articles
      were selected according to the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses criteria. Articles reporting on direct costs of RP (open
      retropubic [RRP], radical perineal [RPP], laparoscopic [LRP], RALP) in men with
      clinically localized PCa were eligible for study inclusion. EVIDENCE SYNTHESIS:
      Of 1218 articles initially screened by title, the multistep, systematic search
      identified 11 studies presenting direct costs of different approaches to RP. Of
      the 11 studies, 7 compared the costs of different RP approaches. Minimally
      invasive RP (MIRP) (ie, LRP or RALP) was more expensive than RRP in most studies,
      mainly due to increased surgical instrumentation costs. In the comparative
      studies, costs ranged from (in US dollars) $5058 to $11,806 for MIRP and from
      $4075 to $6296 for RRP, with RALP having the highest direct costs. In one study
      applying standardized, health economic-evaluation criteria, RALP was not found to
      be cost effective. Limitations of this review include significant differences in
      observational study designs and an absence of prospective comparative studies.
      Moreover, there are limited post-RP data on the costs of adjuvant treatments and
      other health care-related expenses after PCa surgery. CONCLUSIONS: Few studies
      compared direct costs of different approaches to RP. The use of new technology,
      particularly RALP, results in added costs for the procedure. Cost effectiveness
      of new technologies should be assessed before widespread adoption. To date, in
      the lone study to evaluate this, RALP was not found to be cost effective from a
      health care, economic standpoint. However, longer follow-up of patients is
      required to better evaluate its impact on overall costs and quality of PCa care.

PMID- 22981674
TI  - In-hospital mortality and failure to rescue after cytoreductive nephrectomy.
AB  - BACKGROUND: The risk of in-hospital mortality after cytoreductive nephrectomy
      (CNT) is non-negligible and may vary widely according to various patient and
      hospital characteristics and clinical contexts. OBJECTIVE: To better elucidate
      the mechanisms underlying variability in operative mortality after CNT. DESIGN,
      SETTING, AND PATIENTS: Using the US-based Nationwide Inpatient Sample registry, a
      weighted estimate of 16 285 patients with metastatic renal cell carcinoma (mRCC)
      treated with CNT between 1998 and 2007 was made retrospectively. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Failure to rescue (FTR), defined as the
      number of deaths in patients who developed an adverse outcome during
      hospitalization. Univariable and multivariable logistic regression models were
      used. RESULTS: Of all 16 285 mRCC patients who underwent a CNT, 31% had an
      occurrence of one complication or more. The overall FTR rate was 5% and differed
      significantly according to age (>= 75 yr vs <75 yr: 7.9% vs 4.3%) and
      comorbidities (>= 3 vs 0: 7.7% vs 4.8%), as well as hospital bed size (small vs
      large: 7.2% vs 5.3%, all p <= 0.03). Patients who had an occurrence of infections
      (19.3%), cardiac- (15.7%), respiratory- (11.4%), or vascular-related
      complications (16.5%) had significantly higher FTR rates. It is noteworthy that
      increasing hospital volume and number of hospital beds also corresponded to lower
      rates of FTR after adjusting for other covariates. CONCLUSIONS: Following CNT for
      mRCC, the occurrence of infections, cardiac-, respiratory-, or vascular-related
      complications resulted in higher FTR rates. Hospitals with greater number of beds
      and higher annual hospital volume had lower FTR rates, confirming the concepts
      that support FTR as an indicator for better quality of care following a high-risk
      surgical procedure.

PMID- 22981677
TI  - Effects of mirabegron, a novel beta3-adrenoceptor agonist, on primary bladder
      afferent activity and bladder microcontractions in rats compared with the effects
      of oxybutynin.
AB  - BACKGROUND: Mirabegron is the first beta3-adrenoceptor agonist that is clinically
      effective for overactive bladder. OBJECTIVE: The effects of mirabegron on primary
      bladder mechanosensitive single-unit afferent activities (SAAs) and bladder
      microcontractions were evaluated and compared with the effects of oxybutynin.
      DESIGN, SETTING, AND PARTICIPANTS: Female Sprague-Dawley rats were anesthetized.
      The SAAs generated from left L6 dorsal roots were identified by electrical
      stimulation of the left pelvic nerve and bladder distension. Nerves with
      conduction velocities (CVs) >2.5 m/s were designated as Adelta-fibers, and nerves
      with CVs<2.5 m/s were designated as C-fibers. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Two measurements were performed in separate animals. First,
      after measuring the baselines of SAA during constant filling cystometry, the
      procedure was repeated with each intravenous administration of mirabegron at
      three doses-0.1, 0.3, and 1.0mg/kg-cumulatively. Second, the bladder was filled
      with saline until the intravesical pressure reached 30 cm H(2)O and was kept
      under an isovolumetric condition; then the recording was performed for 5 min with
      vehicle and mirabegron or oxybutynin administrated intravenously. RESULTS AND
      LIMITATIONS: A total of 74 single-unit afferent fibers were isolated from 55 rats
      (Adelta-fibers: n=34; C-fibers: n=40). SAAs of both Adelta-fibers and C-fibers in
      response to bladder filling significantly decreased after mirabegron
      administration in a dose-dependent manner, which was more remarkable for Adelta
      fibers. During an isovolumetric condition of the bladder, the mean bladder
      pressure and the number of microcontractions decreased after mirabegron
      administration, whereas these parameters did not change with oxybutynin
      administration. SAAs of Adelta-fibers were significantly decreased by mirabegron
      administration at both 0.3 and 1mg/kg, whereas SAAs of C-fibers decreased only at
      1mg/kg. In contrast, oxybutynin (1mg/kg) did not alter either type of SAA.
      CONCLUSIONS: The present study demonstrates that mirabegron can inhibit
      mechanosensitive bladder afferent activity, especially of Adelta-fibers, which
      may be related to suppression of bladder microcontractions.

PMID- 22981675
TI  - Targeted next-generation sequencing of advanced prostate cancer identifies
      potential therapeutic targets and disease heterogeneity.
AB  - BACKGROUND: Most personalized cancer care strategies involving DNA sequencing are
      highly reliant on acquiring sufficient fresh or frozen tissue. It has been
      challenging to comprehensively evaluate the genome of advanced prostate cancer
      (PCa) because of limited access to metastatic tissue. OBJECTIVE: To demonstrate
      the feasibility of a novel next-generation sequencing (NGS)-based platform that
      can be used with archival formalin-fixed paraffin-embedded (FFPE) biopsy tissue
      to evaluate the spectrum of DNA alterations seen in advanced PCa. DESIGN,
      SETTING, AND PARTICIPANTS: FFPE samples (including archival prostatectomies and
      prostate needle biopsies) were obtained from 45 patients representing the
      spectrum of disease: localized PCa, metastatic hormone-naive PCa, and metastatic
      castration-resistant PCa (CRPC). We also assessed paired primaries and metastases
      to understand disease heterogeneity and disease progression. INTERVENTION: At
      least 50 ng of tumor DNA was extracted from FFPE samples and used for
      hybridization capture and NGS using the Illumina HiSeq 2000 platform. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: A total of 3320 exons of 182 cancer
      associated genes and 37 introns of 14 commonly rearranged genes were evaluated
      for genomic alterations. RESULTS AND LIMITATIONS: We obtained an average
      sequencing depth of >900X. Overall, 44% of CRPCs harbored genomic alterations
      involving the androgen receptor gene (AR), including AR copy number gain (24% of
      CRPCs) or AR point mutation (20% of CRPCs). Other recurrent mutations included
      transmembrane protease, serine 2 gene (TMPRSS2):v-ets erythroblastosis virus E26
      oncogene homolog (avian) gene (ERG) fusion (44%); phosphatase and tensin homolog
      gene (PTEN) loss (44%); tumor protein p53 gene (TP53) mutation (40%);
      retinoblastoma gene (RB) loss (28%); v-myc myelocytomatosis viral oncogene
      homolog (avian) gene (MYC) gain (12%); and phosphatidylinositol-4,5-bisphosphate
      3-kinase, catalytic subunit alpha gene (PIK3CA) mutation (4%). There was a high
      incidence of genomic alterations involving key genes important for DNA repair,
      including breast cancer 2, early onset gene (BRCA2) loss (12%) and ataxia
      telangiectasia mutated gene (ATM) mutations (8%); these alterations are
      potentially targetable with poly(adenosine diphosphate-ribose)polymerase
      inhibitors. A novel and actionable rearrangement involving the v-raf murine
      sarcoma viral oncogene homolog B1 gene (BRAF) was also detected. CONCLUSIONS:
      This first-in-principle study demonstrates the feasibility of performing in-depth
      DNA analyses using FFPE tissue and brings new insight toward understanding the
      genomic landscape within advanced PCa.

PMID- 22981678
TI  - Ante- and postpartum redox status of blood in women with inherited thrombophilia
      treated with heparin.

PMID- 22981679
TI  - Coordination of the non-paretic leg during hemiparetic gait: expected and novel
      compensatory patterns.
AB  - BACKGROUND: Post-stroke hemiparesis is usually considered a unilateral motor
      control deficit of the paretic leg, while the non-paretic leg is assumed to
      compensate for paretic leg impairments and have minimal to no deficits. While the
      non-paretic leg electromyography (EMG) patterns are clearly altered, how the non
      paretic leg acts to compensate remains to be established. METHODS: Kinesiological
      data were recorded from sixty individuals with chronic hemiparesis (age: 60.9,
      SD=12.6 years, 21 females, 28 right hemiparetic, time since stroke: 4.5 years, SD
      3.9 years), divided into three speed-based groups, and twenty similarly aged
      healthy individuals (age: 65.1, SD=10.4 years, 15 females). All walked on an
      instrumented split-belt treadmill at their self-selected speed and control
      subjects also walked at slower speeds matching those of the persons with
      hemiparesis. We determined the differences in magnitude and timing of non-paretic
      EMG activity relative to healthy control subjects in four pre-defined regions of
      stance phase of the gait cycle. FINDINGS: Integrated EMG activity and EMG timing
      in the non-paretic leg were different in many muscles. Multiple compensatory
      patterns identified included: increased EMG output when the muscle was typically
      active in controls and novel compensatory EMG patterns that appeared to provide
      greater propulsion or support with little evidence of impaired motor performance.
      INTERPRETATION: Most novel compensations were made possible by altered kinematics
      of the paretic and non-paretic leg (i.e., early stance plantarflexor activity
      provided propulsion due to the decreased advancement of the non-paretic foot)
      while others (late single limb stance knee extensor and late stance hamstring
      activity) appeared to be available mechanisms for increasing propulsion.

PMID- 22981680
TI  - In vitro biomechanical study of femoral torsion disorders: effect on femoro
      tibial kinematics.
AB  - BACKGROUND: Gonarthrosis is a degenerative disease mainly found in elderly
      persons. Frontal plane deviations are known to induce lateral and medial
      gonarthrosis. Nevertheless, patients suffer from gonarthrosis without frontal
      deviations. Lower limb torsions disorders have been considered as a factor
      inducing lateral and medial gonarthrosis. This paper reports an in vitro study
      aiming at quantifying the relationships between experimental femoral torsion
      disorders and femoro-tibial kinematics. METHODS: Five fresh-frozen lower limbs
      were used. Specimens were fixed on an experimental jig and muscles were loaded. A
      six-degree-of-freedom Instrumented Spatial Linkage was used to measure femoro
      tibial kinematics. Experimental femoral osteotomies were performed to simulate
      various degrees of medial and lateral torsion. Internal tibial rotation,
      abduction/adduction and proximo-distal, medio-lateral and antero-posterior
      translations were measured during knee flexion. FINDINGS: Internal tibial
      rotation and abduction/adduction were significantly influenced (P<0.001) by
      femoral torsion disorder conditions. Medial femoral torsion increased tibial
      adduction and decreased internal rotation during knee flexion. Opposite changes
      were observed during lateral femoral torsion. Concerning translations, medial
      femoral torsion induced a significant (P<0.05) decrease of medial translation and
      inversely for lateral femoral torsion. No interactions between femoral torsion
      disorders and range of motion were observed. INTERPRETATION: Our results showed
      that medial and lateral femoral torsion disorders induced alterations of femoro
      tibial kinematics when applied in normally aligned lower limbs. These results
      highlight a potential clinical relevance of the effect of femoral torsion
      alterations on knee kinematics that may be related to the development of long
      term knee disease.

PMID- 22981681
TI  - Gene therapy for primary immunodeficiencies: Part 1.
AB  - Over 60 patients affected by SCID due to IL2RG deficiency (SCID-X1) or adenosine
      deaminase (ADA)-SCID have received hematopoietic stem cell gene therapy in the
      past 15 years using gammaretroviral vectors, resulting in immune reconstitution
      and clinical benefit in the majority of them. However, the occurrence of
      insertional oncogenesis in the SCID-X1 trials has led to the development of new
      clinical trials based on integrating vectors with improved safety design as well
      as investigation on new technologies for highly efficient gene targeting and site
      specific gene editing. Here we will present the experience and perspectives of
      gene therapy for SCID-X1 and ADA-SCID and discuss the pros and cons of gene
      therapy in comparison to allogeneic transplantation.

PMID- 22981682
TI  - Eosinophil extracellular DNA traps: molecular mechanisms and potential roles in
      disease.
AB  - Eosinophil extracellular traps (EETs) are part of the innate immune response and
      are seen in multiple infectious, allergic, and autoimmune eosinophilic diseases.
      EETs are composed of a meshwork of DNA fibers and eosinophil granule proteins,
      such as major basic protein (MBP) and eosinophil cationic protein (ECP).
      Interestingly, the DNA within the EETs appears to have its origin in the
      mitochondria of eosinophils, which had released most their mitochondrial DNA, but
      were still viable, exhibiting no evidence of a reduced life span. Multiple
      eosinophil activation mechanisms are represented, whereby toll-like, cytokine,
      chemokine, and adhesion receptors can all initiate transmembrane signal
      transduction processes leading to the formation of EETs. One of the key signaling
      events required for DNA release is the activation of the NADPH oxidase. Here, we
      review recent progress made in the understanding the molecular mechanisms
      involved in DNA and granule protein release, discuss the presence of EETs in
      disease, speculate on their potential role(s) in pathogenesis, and compare
      available data on other DNA-releasing cells, particularly neutrophils.

PMID- 22981683
TI  - Development of asthma is determined by the age-dependent host response to
      respiratory virus infection: therapeutic implications.
AB  - Lower respiratory tract virus infections are the major cause of asthma
      exacerbations. Severity of infection and age at initial encounter with virus
      appear to be major determinants of the risk for allergic asthma later in life. In
      animal models, reinfection of mice initially infected as neonates leads to
      markedly enhanced alterations in airway function and inflammation, unlike
      reinfection of older mice. Both innate and adaptive immune responses contribute
      to this susceptibility with lung dendritic cells showing marked differences in
      phenotype and function in young compared to older mice, and these differences are
      further enhanced following virus infection. These findings have implications for
      therapeutic targeting, for example, of RSV G and F surface proteins at different
      stages of the response to infection.

PMID- 22981684
TI  - Development of nuclease-mediated site-specific genome modification.
AB  - Genome engineering is an emerging strategy to treat monogenic diseases that
      relies on the use of engineered nucleases to correct mutations at the nucleotide
      level. Zinc finger nucleases can be designed to stimulate homologous
      recombination-mediated gene targeting at a variety of loci, including genes known
      to cause the primary immunodeficiencies (PIDs). Recently, these nucleases have
      been used to correct disease-causing mutations in human cells, as well as to
      create new animal models for human disease. Although a number of hurdles remain
      before they can be used clinically, engineered nucleases hold increasing promise
      as a therapeutic tool, particularly for the PIDs.

PMID- 22981685
TI  - Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely
      agitated patient: a multicenter, randomized, double-blind, placebo-controlled
      clinical trial.
AB  - STUDY OBJECTIVE: Parenteral benzodiazepines or antipsychotics are often used to
      manage acute agitation in emergency department (ED) settings in which alternative
      strategies have failed or are not feasible. There are scant data comparing
      parenteral medication regimens. We aim to determine the efficacy and safety of
      intravenous droperidol or olanzapine as an adjunct to intravenous midazolam for
      rapid patient sedation. METHODS: We undertook a randomized, double-blind, placebo
      controlled, double-dummy, clinical trial in 3 EDs (August 2009 to March 2011).
      Adult patients (n=336) requiring intravenous drug sedation for acute agitation
      were randomized to receive a saline solution (control), droperidol (5 mg), or
      olanzapine (5 mg) bolus. This was immediately followed by incremental intravenous
      midazolam boluses (2.5 to 5 mg) until sedation was achieved. The primary outcome
      was time to sedation. Secondary outcomes were need for "rescue" drugs and adverse
      events. RESULTS: Three hundred thirty-six patients were randomized to the 3
      groups. Baseline characteristics were similar across groups. The differences in
      medians for times to sedation between the control and droperidol and control and
      olanzapine groups were 4 minutes (95% confidence interval [CI] 1 to 6 minutes)
      and 5 minutes (95% CI 1 to 6 minutes), respectively. At any point, patients in
      the droperidol and olanzapine groups were approximately 1.6 times more likely to
      be sedated compared with controls: droperidol and olanzapine group hazard ratios
      were 1.61 (95% CI 1.23 to 2.11) and 1.66 (95% CI 1.27 to 2.17), respectively.
      Patients in the droperidol and olanzapine groups required less rescue or
      alternative drug use after initial sedation. The 3 groups' adverse event profiles
      and lengths of stay did not differ. CONCLUSION: Intravenous droperidol or
      olanzapine as an adjunct to midazolam is effective and decreases the time to
      adequate sedation compared with midazolam alone.

PMID- 22981686
TI  - Boys affiliate more than girls with a familiar same-sex peer.
AB  - Evidence from ethnographic, observational, and experimental studies with humans
      converges to suggest that males affiliate more than females with unrelated,
      familiar same-sex peers, but this has never been examined directly. With this
      aim, we compared frequency of affiliation with a single, randomly chosen,
      familiar same-sex peer for the two sexes during early childhood. A focal child
      was brought to a room with three play areas-one containing a same-sex peer, one
      containing an adult, and one empty-and time spent with the peer was tabulated.
      Results demonstrated that boys visited the play area with the same-sex peer more
      frequently than girls did, and more boys than girls spent significant amounts of
      time with the peer. Human males' greater willingness to affiliate with randomly
      chosen familiar peers likely contributes to sex differences in a number of
      characteristics of humans' social interactions.

PMID- 22981687
TI  - Competitive molecular interaction among paeonol-loaded liposomes: differential
      scanning calorimetry and synchrotron X-ray diffraction studies.
AB  - Thermotropic phase behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)
      liposomes containing 5 mol% cholesterol, or 5 mol% stigmasterol, or 5 mol%
      paeonol have been investigated by differential scanning calorimetry (DSC) and
      synchrotron X-ray diffraction (XRD) techniques, to investigate the competitive
      molecular interaction among paeonol-loaded liposomes. The results show that both
      sterol and paeonol can incorporate into hydrophobic region and interact with acyl
      chains of DPPC. Both 5 mol% sterols and 5 mol% paeonol can promote the formation
      of rippled gel phase of DPPC liposomes at room temperature. 5 mol% paeonol can
      induce the occurrence of phase separation in DPPC liposomes, but 5 mol%
      cholesterol or 5 mol% stigmasterol cannot induce this phenomenon. Both the repeat
      distance and the correlation length of paeonol-poor domain are larger than those
      of coexisted paeonol-rich domain. Both calorimetric data and SAXS patterns show
      that sterols have more favorable, stabilizing interactions with DPPC than
      paeonol, implying that high concentrations of sterols will have a negative effect
      on the loading of paeonol. In addition, calorimetric data show that cholesterol
      have a little more favorable, stabilizing interactions with DPPC than
      stigmasterol. The results of this study will play an important role in optimizing
      the formulation of paeonol-loaded liposomes.

PMID- 22981688
TI  - Electrospun drug-loaded core-sheath PVP/zein nanofibers for biphasic drug
      release.
AB  - Core-sheath nanofibers prepared using coaxial electrospinning were investigated
      for providing biphasic drug release profiles. With ketoprofen (KET) as the model
      drug, polyvinylpyrrolidone and zein as the sheath polymer and core matrix,
      respectively, the coaxial process could be carried out smoothly and continuously
      without any clogging of the spinneret. Scanning electron microscopy and
      transmission electron microscopy observations demonstrated that the nanofibers
      were linear with homogeneous structure and had a clear core-sheath structure with
      an average diameter of 730 +/- 190 nm, in which the sheath had a thickness of ca.
      90 nm. Differential scanning calorimetric and X-ray diffraction analyses verified
      that all the components in the core-sheath nanofibers were present in an
      amorphous state. Attenuated total reflectance Fourier transform infrared spectra
      demonstrated both the sheath and core matrix had good compatibility with KET
      owing to hydrogen bonding. In vitro dissolution tests showed that the nanofibers
      could provide an immediate release of 42.3% of the contained KET, followed by a
      sustained release over 10h of the remaining drug. The present study exhibited a
      simple and useful approach to systematically design and fabricate nanostructures
      using coaxial electrospinning for providing biphasic drug release profiles.

PMID- 22981689
TI  - Preparation and evaluation of liposome-encapsulated codrug LMX.
AB  - A novel codrug (LMX) consisting of Lamivudine and Ursolic acid has been shown to
      possess the dual action of anti-hepatitis B virus activity and hepatoprotective
      effects against acute liver injury in vivo. Because of the limited water
      solubility of LMX, our aims were to design and optimize a liposomal formulation
      that could facilitate its in vivo administration, and to estimate the potential
      of LMX-loaded liposomes as oral or intravenous delivery system. In this work, LMX
      loaded liposomes were prepared by the thin film hydration method coupled with
      sonication. LMX-loaded liposomes showed spherical morphology under transmission
      electron microscope (TEM) analysis. The mean particle size of liposomes was about
      210 nm, and the drug entrapment efficiency was more than 90%. Stability data
      indicated that lyophilized liposomes were stable for at least 6 months at 4 
      degrees C. In vitro drug release profile of LMX-loaded liposomes showed a
      sustained release profile of LMX and an initial mild burst was observed. The
      relative bioavailability of LMX-loaded liposomes was 1074.8% compared with LMX
      suspension after oral administration, and 135.2% relative to 50% alcohol solution
      after intravenous (i.v.) administration. These results indicated that LMX-loaded
      liposomes were valued to develop as a practical preparation for oral or i.v.
      administration.

PMID- 22981690
TI  - Effects of metallic cranioplasty on electroencephalographic recordings: an
      illustrative case.

PMID- 22981691
TI  - Indoleamine 2,3-dioxygenase activity and expression in patients with chronic
      lymphocytic leukemia.
AB  - Indoleamine 2,3-dioxygenase (IDO) activity and expression is increased in many
      hematological malignancies, but has not been previously studied in chronic
      lymphocytic leukemia (CLL). We determined IDO activity and expression in 49
      patients with CLL. We found that IDO activity is increased in CLL. This may have
      some influence on CLL progression. BACKGROUND: Indoleamine 2,3-dioxygenase (IDO)
      is an enzyme involved in the catabolism of tryptophan, suppressing T-cell
      activity. IDO activity and expression are increased in many malignant diseases,
      including hematological malignancies. IDO expression can mediate immunotolerance
      to tumors. IDO activity and expression have not previously been studied in
      chronic lymphocytic leukemia (CLL). METHODS: We measured IDO activity by
      calculating the kynurenine-tryptophan (kyn-trp) ratio. IDO and IDO2 gene
      expression was determined by using real-time polymerase chain reaction (PCR).
      RESULTS: In patients with CLL, the serum kyn-trp ratio--reflecting increased IDO
      activity--was significantly higher compared with controls, but in peripheral
      blood mononuclear cells (PBMCs)--mainly representing malignant B cells--the
      expression of genes encoding IDO and IDO2 enzymes was reduced. CONCLUSIONS:
      Increased IDO activity in patients with CLL may affect disease progression,
      although it originates from cells other than malignant B cells.

PMID- 22981693
TI  - Neonatal domoic acid treatment produces alterations to prepulse inhibition and
      latent inhibition in adult rats.
AB  - Schizophrenia is a complex and severe mental disorder characterized by positive,
      negative and cognitive symptoms. Characteristic behavioral alterations reflecting
      these categories of symptoms have been observed in many animal models of this
      disorder, and are consistent with those manifested in the clinical population.
      The purpose of this study was to determine whether early alterations in glutamate
      signaling would result in alterations to prepulse inhibition (PPI) and latent
      inhibition (LI); two assessments used for evaluating putative novel animal models
      with relevance to schizophrenia. In the present experiment, daily subcutaneous
      (s.c.) injections of 20MUg/kg of domoic acid (DOM) were administered to rat pups
      from postnatal days (PND) 8-14. When tested as adults, DOM treated rats displayed
      deficits in PPI that were dependant on both sex and time of day. No differences
      in startle amplitude, habituation, or movement were found during any test,
      indicating that the PPI deficits seen could not be attributed to baseline startle
      differences. Deficits in LI were also apparent when adult rats were tested using
      a conditioned taste aversion task, with DOM-treated animals displaying a
      significantly suppressed LI. These results suggest that early treatment with DOM
      may serve as a useful tool to model schizophrenia which in turn may lead to a
      better understanding of the contribution of glutamate, and in particular, kainate
      receptors, to the development and/or manifestation of schizophrenia or
      schizophrenia-like symptoms in the clinical population.

PMID- 22981692
TI  - Dynamic and coordinated epigenetic regulation of developmental transitions in the
      cardiac lineage.
AB  - Heart development is exquisitely sensitive to the precise temporal regulation of
      thousands of genes that govern developmental decisions during differentiation.
      However, we currently lack a detailed understanding of how chromatin and gene
      expression patterns are coordinated during developmental transitions in the
      cardiac lineage. Here, we interrogated the transcriptome and several histone
      modifications across the genome during defined stages of cardiac differentiation.
      We find distinct chromatin patterns that are coordinated with stage-specific
      expression of functionally related genes, including many human disease-associated
      genes. Moreover, we discover a novel preactivation chromatin pattern at the
      promoters of genes associated with heart development and cardiac function. We
      further identify stage-specific distal enhancer elements and find enriched DNA
      binding motifs within these regions that predict sets of transcription factors
      that orchestrate cardiac differentiation. Together, these findings form a basis
      for understanding developmentally regulated chromatin transitions during lineage
      commitment and the molecular etiology of congenital heart disease.

PMID- 22981694
TI  - The effect of intra-nucleus accumbens administration of allopregnanolone on delta
      and gamma2 GABA(A) receptor subunit mRNA expression in the hippocampus and on
      depressive-like and grooming behaviors in rats.
AB  - Alterations in GABA(A) receptor expression have been associated with the
      allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; 3alpha,5alpha-THP)
      antidepressant-like effect in rats. The present study aimed to verify the effect
      of bilateral, intra-nucleus accumbens core (intra-AcbC) administration of the
      neurosteroid allopregnanolone on behaviors in the forced swim and grooming
      microstructure tests and in the delta and gamma2 GABA(A) receptor subunit mRNA
      expression in right and left hippocampus of rats. The results of this study
      showed that bilateral, intra-AcbC allopregnanolone administration (5MUg/rat)
      presented antidepressant-like activity in the forced swim test concomitant with
      an increase in climbing. Allopregnanolone at doses of 1.25 and 5MUg/rat also
      decreased the percentage of correct transitions in the grooming microstructure
      test. Both delta and gamma2 GABA(A) subunit expressions increased in the rat
      hippocampus after allopregnanolone intra-AcbC treatment. Our findings point to
      asymmetrical GABA(A) receptor expression changes in the hippocampus of animals
      treated with allopregnanolone. Further investigation should evaluate the
      antidepressant-like effect of allopregnanolone not only in other directly infused
      regions but also with respect to changes in other brain areas of the limbic
      system to understand allopregnanolone's mechanism of action.

PMID- 22981695
TI  - Distinct regions within fibulin-1D modulate interactions with hemicentin.
AB  - Fibulins are evolutionarily conserved extracellular matrix (ECM) proteins that
      assemble in elastic fibers and basement membranes. Caenorhabditis elegans has a
      single fibulin gene that produces orthologs of vertebrate fibulin-1 C and D
      splice forms. In a structure-function analysis of fibulin-1 domains, a series of
      deletion constructs show that EGF repeats 4 and 5 are required for the hemicentin
      dependent assembly and function of fibulin-1D in native locations. In contrast,
      constructs missing the second EGF repeat of fibulin-1D (EGF2D) assemble in
      ectopic locations in a hemicentin dependent manner. Constructs that contain EGF2D
      are cleaved into two fragments, but constructs with EGF2D missing are not,
      suggesting that a protease binds and/or cleaves fibulin-1D at a site that is
      likely within EGF2D. Together, the data suggests that EGF repeats 4 and 5 promote
      interaction with hemicentin while a region within EGF2D suppresses ectopic
      interactions with hemicentin and this suppression may be protease dependent.

PMID- 22981696
TI  - History of blood transfusion in sub-saharan Africa.
AB  - The adequacy and safety of blood transfusion in sub-Saharan Africa is the subject
      of much concern, yet there have been very few studies of its history. An overview
      of that record finds that transfusions were first reported in Africa (sub-Saharan
      and excluding South Africa) in the early 1920s, and organized transfusion
      practices were established before the Second World War. Blood transfusion grew
      rapidly after 1945, along with the construction of new hospitals and expanded
      health services in Africa. Significant differences existed between colonial
      powers in the organization of transfusion services, but these converged after
      independence as their use continued to grow and decentralized and hospital-based
      practices were adopted. It was only after the oil crisis in the mid-1970s that
      health spending declined and the collection, testing, and transfusion of blood
      began to level off. Thus, when the AIDS crisis hit transfusion services, they
      were already struggling to meet the needs of patients. At this time, foreign
      assistance as well as the World Health Organization and the League of Red Cross
      Societies helped respond to both the immediate problem of testing blood, and for
      some countries, support existed for the broader reorganization of transfusion.
      Overall, the history shows that transfusion was adopted widely and quickly,
      limited mainly by the availability of knowledgeable doctors and hospital
      facilities. There was less resistance than expected by Africans to receive
      transfusions, and the record shows a remarkable flexibility in obtaining blood.
      The dangers of disease transmission were recognized from an early date but were
      balanced against the potential lifesaving benefits of transfusion.

PMID- 22981697
TI  - Spinal muscular atrophy at the crossroads of basic science and therapy.

PMID- 22981698
TI  - When does change begin following screening and brief intervention among depressed
      problem drinkers?
AB  - Brief interventions are effective for problem drinking and reductions are known
      to occur in association with screening and assessment. The present study sought
      to assess, among participants (N=202) in a clinical trial, how much change
      occurred between baseline assessment and a one-session brief intervention (S1),
      and the predictors of early change. The primary focus was on changes in the Beck
      Depression Inventory Fast Screen scores and alcohol consumption (standard drinks
      per week) prior to random allocation to nine further sessions addressing either
      depression, alcohol, or both problems. There were large and clinically
      significant reductions between baseline and S1, with the strongest predictors
      being baseline scores in the relevant domain and change in the other domain.
      Client engagement was also predictive of early depression changes. Monitoring
      progress in both domains from first contact, and provision of empathic care,
      followed by brief intervention appear to be useful for this high prevalence
      comorbidity.

PMID- 22981699
TI  - The oxidative denitrosylation mechanism and nitric oxide release from human fetal
      and adult hemoglobin, an experimentally based model simulation study.
AB  - Generation of unbound nitric oxide (NO) via the oxidative denitrosylation (ODN)
      mechanism is proposed to involve the simultaneous reaction of nitrite with oxy
      and deoxy hemoglobin (Hb(O2) (k1) and Hb (k13)) to yield respectively, *NO2 and
      Hb(+2)(NO). These two reaction pathways are coupled when *NO2 reacts with
      Hb(+2)(NO) to yield Hb(+3)(NO) (k22), a species that releases NO rapidly. Here, I
      have constructed an experimentally based molecular model of the ODN mechanism (k1
      k31), focusing on the high nitrite reductase activity of R-state hemoglobin. This
      model was used to test the hypothesis that human fetal hemoglobin (HbF) can
      generate unbound NO faster and to a greater extent than HbA, consequent to a 25
      fold larger value of k1, which was determined in an earlier study. The results
      show that despite the use of identical values for k22, there was a 44-fold larger
      apparent rate of reaction of *NO2 with HbF(NO) compared to HbA(NO), for reactions
      simulated at 410 MUM nitrite and 100 MUM hemoglobin (heme basis), 50% oxygen
      saturation at pH 7.4 and 37 degrees C. This faster reaction was associated with
      the generation of about 11 MUM peak unbound NO. In contrast, HbA failed to
      generate unbound NO rapidly under the same conditions. However, raising the
      concentration of nitrite into the millimolar range did generate unbound NO in the
      HbA simulation, in agreement with the experimental literature, and that result
      was associated with acceleration in the rate of reaction of NO2 with HbA(NO).
      Unbound NO could be generated at 410 MUM nitrite in the HbA simulation by
      lowering the pH. This too was associated with an acceleration in the rate of
      reaction of NO2 with HbA(NO). Furthermore, generation of unbound NO could be
      assigned to the pH-dependent increase in k1, independent of the associated
      increase in k(13). Finally, selective exchange of the HbA value of k1 for the HbF
      value, keeping all other constants and conditions unchanged, generated kinetic
      patterns for the various species of the "k1-modified" HbA simulation, which were
      virtually indistinguishable from those seen in the HbF simulation. Taken
      together, these findings show that rapid and extensive generation of unbound NO
      within the ODN mechanism is controlled by the value of k1. The faster and more
      extensive generation of unbound NO by HbF at micromolar nitrite concentration
      suggests a possible second function for HbF in sickle cell disease, namely
      enhanced vasodilation. The failure of 410 MUM nitrite to generate unbound NO in
      the HbA simulation at pH 7.4, contrasts with evidence in the literature showing
      that exposure of intact red cells to 100 to 200 MUM nitrite in PBS, promoted NO
      release into the gas phase. I point out that this difference in outcome may be
      due to the higher activity of HbA when bound to the cytoplasmic domain of the red
      cell membrane anion transport protein SLC4A1 (band 3) and to the demonstrated
      capacity of band 3 to transport nitrite.

PMID- 22981701
TI  - Quantitative evaluation of a hydrophilic matrix intravaginal ring for the
      sustained delivery of tenofovir.
AB  - In vitro testing and quantitative analysis of a matrix, hydrophilic polyether
      urethane (HPEU) intravaginal ring (IVR) for sustained delivery of the anti-HIV
      agent tenofovir (TFV) are described. To aid in device design, we employed a
      pseudo-steady-state diffusion model to describe drug release, as well as an
      elastic mechanical model for ring compression to predict mechanical properties.
      TFV-HPEU IVRs of varying sizes and drug loadings were fabricated by hot-melt
      extrusion and injection molding. In vitro release rates of TFV were measured at
      37  degrees C and pH 4.2 for 30 or 90 days, during which times IVR mechanical
      properties and swelling kinetics were monitored. Experimental data for drug
      release and mechanical properties were compared to model predictions. IVRs loaded
      with 21% TFV (w/w) released greater than 2mg TFV per day for 90 days. The
      diffusion model predicted 90 day release data by extrapolating forward from the
      first 7 days of data. Mechanical properties of IVRs were similar to NuvaRing,
      although the matrix elastic modulus decreased up to three-fold following
      hydration. This is the first vaginal dosage form to provide sustained delivery of
      milligram quantities of TFV for 90 days. Drug release and mechanical properties
      were approximated by analytical models, which may prove useful for the continuing
      development of IVRs for HIV prevention or other women's health indications.

PMID- 22981700
TI  - Transfusion immunomodulation--the case for leukoreduced and (perhaps) washed
      transfusions.
AB  - During the last three decades, a growing body of clinical, basic science and
      animal model data has demonstrated that blood transfusions have important effects
      on the immune system. These effects include: dysregulation of inflammation and
      innate immunity leading to susceptibility to microbial infection, down-regulation
      of cellular (T and NK cell) host defenses against tumors, and enhanced B cell
      function that leads to alloimmunization to blood group, histocompatibility and
      other transfused antigens. Furthermore, transfusions alter the balance between
      hemostasis and thrombosis through inflammation, nitric oxide scavenging, altered
      rheologic properties of the blood, immune complex formation and, no doubt,
      several mechanisms not yet elucidated. The net effects are rarely beneficial to
      patients, unless they are in imminent danger of death due to exsanguination or
      life threatening anemia. These findings have led to appeals for more conservative
      transfusion practice, buttressed by randomized trials showing that patients do
      not benefit from aggressive transfusion practices. At the risk of hyperbole, one
      might suggest that if the 18th and 19th centuries were characterized by
      physicians unwittingly harming patients through venesection and bleeding, the
      20th century was characterized by physicians unwittingly harming patients through
      current transfusion practices. In addition to the movement to more parsimonious
      use of blood transfusions, an effort has been made to reduce the toxic effects of
      blood transfusions through modifications such as leukoreduction and saline
      washing. More recently, there is early evidence that reducing the storage period
      of red cells transfused might be a strategy for minimizing adverse outcomes such
      as infection, thrombosis, organ failure and mortality in critically ill patients
      particularly at risk for these hypothesized effects. The present review will
      focus on two approaches, leukoreduction and saline washing, as means to reduce
      adverse transfusion outcomes.

PMID- 22981702
TI  - Compared outcomes after percutaneous pinning versus open reduction in paediatric
      supracondylar elbow fractures.
AB  - BACKGROUND: Supracondylar fractures of the elbow are common in children. Their
      treatment is controversial when displacement has occurred, although percutaneous
      pinning is usually advocated. HYPOTHESIS: In paediatric extension-type
      supracondylar fractures of the elbow, percutaneous pinning and crossed K-wire
      fixation after open reduction via the medial approach produce similar functional
      outcomes and complication rates. MATERIALS AND METHODS: We retrospectively
      reviewed the medical charts of 58 children aged 2 to 15 years who underwent
      surgery for extension-type supracondylar elbow fractures between 2004 and 2008.
      Closed reduction and percutaneous pinning was used in 33 patients with a mean age
      of 7 years and 11 months; open reduction with cross-wiring in 25 patients with a
      mean age of 7 years. Functional outcomes were assessed using Flynn's criteria.
      Baumann's angle was determined and postoperative complications and sequelae were
      recorded. RESULTS: Outcomes were satisfactory in 30 (90.9%) patients treated with
      percutaneous pinning and in 23 (92%) patients treated with open reduction and
      cross-wiring. Mean Baumann's angle at last follow-up was 73.9+/-5.74 degrees 
      after percutaneous pinning and 74.76+/-4.07 degrees  after open reduction and
      cross-wiring. Postoperative complications consisted of reoperation in six (10.3%)
      patients and iatrogenic nerve injury in two (3.4%) patients. Cubitus varus
      occurred in two (6.06%) patients after closed treatment and in one (4%) patient
      after open treatment. In each group, three (5.1%) patients had greater than 15
      degrees  of motion range limitation. DISCUSSION: In children with extension-type
      supracondylar elbow fractures, outcomes are similar with percutaneous pinning and
      with open reduction via the medial approach followed by cross-wiring. LEVEL OF
      EVIDENCE: Level IV, retrospective study.

PMID- 22981703
TI  - Arthroscopic release of shoulder contracture secondary to obstetric brachial
      plexus palsy: retrospective study of 18 children with an average follow-up of 4.5
      years.
AB  - INTRODUCTION: Children affected by obstetric brachial plexus palsy have an
      internal rotation contracture of the shoulder and a deformed glenohumeral joint.
      In 2003, Pearl proposed doing an arthroscopic release of the shoulder to restore
      external rotation and allow the glenohumeral joint to remodel. The goal of the
      current study was to evaluate the active and passive shoulder external rotation
      range of motion and glenohumeral joint remodelling in children treated with
      arthroscopic-directed release. MATERIALS AND METHODS: Between 2004 and 2010, 18
      children with passive external rotation under 10 degrees  were treated with
      shoulder arthroscopy to release the anterior capsule and ligaments and perform a
      subscapularis tenotomy; no tendon transfer was performed. The average age was 4
      years, 2 months. Nine children had an injury at C5C6, four had an injury at
      C5C6C7 and five had a complete injury. The average follow-up was 4.5 years. The
      clinical evaluation consisted of active and passive external rotation (ER) with
      elbow at the side, active internal rotation, and the modified Mallet score. One
      child who required an external rotation osteotomy of the proximal humerus was
      excluded from the clinical outcomes. An MRI was performed on both shoulders to
      assess glenoid retroversion, glenoid type, degree of posterior subluxation
      (measured by the percentage of humeral head anterior to the middle glenoid fossa)
      and humeral head hypoplasia. RESULTS: At the latest follow-up, passive ER was 58
      degrees  on average and active ER was 42 degrees . Eleven children had regained
      more than 30 degrees  of active ER. The average internal rotation had decreased
      after the release. The MRI assessment showed that the glenohumeral joint had
      remodelled in 66% of cases; the glenoid type had improved, the glenoid
      retroversion had diminished and the humeral head was recentred. Humeral head
      hypoplasia was found in 28% of cases. DISCUSSION AND CONCLUSION: Arthroscopic
      release of the shoulder results in more external rotation and allows for
      glenohumeral joint remodelling. Tendon transfer is not always necessary to
      restore active external rotation. LEVEL OF EVIDENCE: Level IV - Retrospective
      study.

PMID- 22981704
TI  - Comparison of metabolic profiles of acutely ill and short-term weight recovered
      patients with anorexia nervosa reveals alterations of 33 out of 163 metabolites.
AB  - Starvation represents an extreme physiological state and entails numerous
      endocrine and metabolic adaptations. The large-scale application of metabolomics
      to patients with acute anorexia nervosa (AN) should lead to the identification of
      state markers characteristic of starvation in general and of the starvation
      specifically associated with this eating disorder. Novel metabolomics technology
      has not yet been applied to this disorder. Using a targeted metabolomics
      approach, we analysed 163 metabolite concentrations in 29 patients with AN in the
      acute stage of starvation (T0) and after short-term weight recovery (T1). Of the
      163 metabolites of the respective kit, 112 metabolites were quantified within
      restrictive quality control limits. We hypothesized that concentrations are
      different in patients in the acute stage of starvation (T0) and after weight gain
      (T1). Furthermore, we compared all 112 metabolite concentrations of patients at
      the two time points (T0, T1) with those of 16 age and gender matched healthy
      controls. Thirty-three of the metabolite serum levels were found significantly
      different between T0 and T1. At the acute stage of starvation (T0) serum
      concentrations of 90 metabolites differed significantly from those of healthy
      controls. Concentrations of controls mostly differed even more strongly from
      those of AN patients after short-term weight recovery than at the acute stage of
      starvation. We conclude that AN entails profound and longer lasting alterations
      of a large number of serum metabolites. Further studies are warranted to
      distinguish between state and trait related alterations and to establish
      diagnostic sensitivity and specificity of the thus altered metabolites.

PMID- 22981705
TI  - Fingerprinting of the TLR4-induced acute inflammatory response.
AB  - Intensive scientific efforts in the past decades have helped shed light into the
      pathogenesis of endotoxin-induced inflammation. We have used multiplexing bead
      based assays to characterize the responses in two models of in vivo LPS
      challenge. C57BL/6 mice were either injected intraperitoneally (endotoxemia) or
      intratracheally (acute lung injury; ALI) with lipopolysaccharide (LPS). The time
      courses (1h-24h) of the following 20 inflammatory mediators in plasma or broncho
      alveolar lavages were simultaneously analyzed: IL-1alpha, IL-1beta, IL-2, IL-3,
      IL-4, IL-5, IL-6, IL-9, IL-12(p40), IL-13, Eotaxin (CCL11), G-CSF, GM-CSF, IFN
      gamma, KC (CXCL1), MCP-1 (CCL2), MIP-1alpha (CCL3), MIP-1beta (CCL4), RANTES
      (CCL5) and TNF-alpha. While significant inductions of all mediators were found,
      substantial differences in their absolute concentrations, time points of maximal
      concentrations and clearances were observed. There were also notable variations
      in the patterns of several cytokines/chemokines when samples from endotoxemia and
      LPS-ALI were compared. These data may be helpful in defining analytic strategies
      including selection of optimal time points for studying the host immune response
      to endotoxin.

PMID- 22981706
TI  - Subtype specific risk factor analyses for sporadic human salmonellosis: a case
      case comparison in Lower Saxony, Germany.
AB  - With the intention to deepen the knowledge of the vertical transmission of
      particular subtypes of Salmonella enterica from "the stable to the table" a case1
      case2 analysis in Lower Saxony, Germany, was conducted. The data collection was
      based on standardised telephone interviews with 1741 Salmonella case persons.
      Single-factor-analyses revealed statistically significant associations between S.
      Typhimurium infections and animal keeping (odds ratio (OR): 1.4; 95%-Confidence
      interval (CI): 1.2-1.7), especially rodents (OR 1.5; CI 1.2-2.1), and with
      consumption of meat (OR 1.9; CI 1.3-2.8), raw ground pork (OR 3.0; CI 2.1-4.2)
      and uncooked pork sausage (OR 2.1; CI 1.6-2.9). The S. Typhimurium phage type DT
      104 was associated most with consumption of uncooked pork sausage (OR 3.6; CI 1.3
      8.5). Multiple logistic regression analyses confirmed the associations between S.
      Typhimurium infection and consumption of raw ground pork and with animal contact.
      The results circumstantiate the assumption of raw pork products still being a
      relevant source for S. Typhimurium infections in Germany. Therefore, it is
      recommended to intensify efforts to reduce salmonella infections caused by raw
      pork products. S. Enteritidis infection was associated statistically
      significantly with travelling abroad (OR 2.1; CI 1.6-3.3), consumption of raw
      tomatoes (OR 1.8; CI 1.5-2.1), dried herbs (OR 2.1; CI 1.0-1.8), and undercooked
      eggs (OR 1.3; CI 1.1-1.6) compared with other serovars. These results were
      confirmed in multiple logistic regression analyses, as well.

PMID- 22981707
TI  - Relative Biologic Effectiveness (RBE) of 50 kV X-rays measured in a phantom for
      intraoperative tumor-bed irradiation.
AB  - PURPOSE: Intraoperative radiation therapy (IORT) with low-energy x-rays is used
      to treat the tumor bed during breast-conserving surgery. The purpose was to
      determine the relative biologic effectiveness (RBE) of 50-kV x-rays for
      inactivation of cells irradiated in a tumor-bed phantom. METHODS AND MATERIALS:
      The RBE was determined for clonogenic inactivation of human tumor and normal
      cells (MCF7, human umbilical vein endothelial cells, normal skin fibroblasts),
      and hamster V79 cells. The 50-kV x-rays from the Intrabeam machine (Carl Zeiss
      Surgical) with a spherical 4-cm applicator were used. Cells were irradiated in a
      water-equivalent phantom at defined distances (8.1-22.9 mm) from the applicator
      surface. The 50-kV x-rays from a surface therapy machine (Dermopan, Siemens) were
      included for comparison; 6-MV x-rays were used as reference radiation. RESULTS:
      At 8.1-mm depth in the phantom (dose rate 15.1 Gy/h), mean RBE values of 50-kV x
      rays from Intrabeam were 1.26 to 1.42 for the 4 cell types at doses yielding
      surviving fractions in the range of 0.01 to 0.5. Confidence intervals were in the
      range of 1.2 and 1.5. Similar RBE values were found for 50-kV x-rays from
      Dermopan for V79 (1.30, CI 1.25-1.36, P=.74) and GS4 (1.42, CI 1.30-1.54, P=.67).
      No significant dependence of RBE on dose was found for Intrabeam, but RBE
      decreased at a larger distance (12.7 mm; 9.8 Gy/h). CONCLUSIONS: An increased
      clinically relevant RBE was found for cell irradiation with Intrabeam at depths
      in the tumor bed targeted by IORT. The reduced RBE values at larger distances may
      be related to increased repair of sublethal damage during protracted irradiation
      or to hardening of the photon beam energy.

PMID- 22981708
TI  - Targeted radiosensitization by the Chk1 inhibitor SAR-020106.
AB  - PURPOSE: To explore the activity of a potent Chk1 inhibitor (SAR-020106) in
      combination with radiation. METHODS AND MATERIALS: Colony and mechanistic in
      vitro assays and a xenograft in vivo model. RESULTS: SAR-020106 suppressed
      radiation-induced G2/M arrest and reduced clonogenic survival only in p53
      deficient tumor cells. SAR-020106 promoted mitotic entry following irradiation in
      all cell lines, but p53-deficient cells were likely to undergo apoptosis or
      become aneuploid, while p53 wild-type cells underwent a postmitotic G1 arrest
      followed by subsequent normal cell cycle re-entry. Following combined treatment
      with SAR-020106 and radiation, homologous-recombination-mediated DNA damage
      repair was inhibited in all cell lines. A significant increase in the number of
      pan-gammaH2AX-staining apoptotic cells was observed only in p53-deficient cell
      lines. Efficacy was confirmed in vivo in a clinically relevant human head-and
      neck cell carcinoma xenograft model. CONCLUSION: The Chk1 inhibitor SAR-020106 is
      a potent radiosensitizer in tumor cell lines defective in p53 signaling.

PMID- 22981709
TI  - Short-term androgen-deprivation therapy improves prostate cancer-specific
      mortality in intermediate-risk prostate cancer patients undergoing dose-escalated
      external beam radiation therapy.
AB  - PURPOSE: We investigated the benefit of short-term androgen-deprivation therapy
      (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose
      escalated external beam radiation therapy. METHODS AND MATERIALS: The present
      retrospective study comprised 710 intermediate-risk PC patients receiving
      external beam radiation therapy with doses of >=81 Gy at a single institution
      from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent
      ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant
      metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional
      hazards models. PC-specific mortality (PCSM) was assessed using competing-risks
      analysis. RESULTS: The median follow-up was 7.9 years. Despite being more likely
      to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National
      Comprehensive Cancer Network intermediate-risk factors, and older age (P<=.001
      for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio
      [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424;
      95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032)
      on univariate analysis. Using multivariate analysis, ADT was an even stronger
      predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739;
      P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95%
      CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and >=50% positive biopsy cores
      were other independent predictors of PCSM. CONCLUSIONS: Short-term ADT improves
      PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose
      escalated external beam radiation therapy.

PMID- 22981710
TI  - Molecular markers predict distant metastases after adjuvant chemoradiation for
      rectal cancer.
AB  - PURPOSE: The outcomes of adjuvant chemoradiation for locally advanced rectal
      cancer are nonuniform among patients with matching prognostic factors. We
      explored the role of molecular markers for predicting the outcome of adjuvant
      chemoradiation for rectal cancer patients. METHODS AND MATERIALS: The study
      included 68 patients with stages II to III rectal adenocarcinoma who were treated
      with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on
      5-fluorouracil and leucovorin was intravenously administered each month for 6-12
      cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions.
      Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase
      (TS), and Raf kinase inhibitor protein (RKIP) was performed. RESULTS: The median
      follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%)
      recurrences occurred. Five-year locoregional failure-free survival (LRFFS),
      distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall
      survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%,
      respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of
      the molecular markers. VEGF overexpression was significantly correlated with
      decreased DMFS (P=.045), while RKIP-positive results were correlated with
      increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2
      (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent
      prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021,
      .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of
      both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased
      DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong
      correlations with improved DFS compared with the rest of the patients (P=.001 and
      <.0001, respectively). CONCLUSIONS: Molecular markers can be valuable in
      predicting treatment outcome of adjuvant chemoradiation for rectal cancer
      patients.

PMID- 22981711
TI  - Combined exercise for people with type 2 diabetes mellitus: a systematic review.
AB  - Type 2 diabetes mellitus has emerged as a major non-communicable chronic diseases
      in many countries. The importance of exercise in the prevention and management of
      this disease is evident. This paper briefly reviews the effects of combining
      aerobic and resistance exercises on glycemic control, and details the training
      and characteristics of various interventions in adults with type 2 diabetes
      mellitus. Literature searches were performed using electronic databases between
      the 1st of January 1950 and the 15th of September 2011. Of the 403 articles
      retrieved, 28 studies met our inclusion criteria. Combined exercise protocols
      seem to improve glycemic control to a greater extent than isolated forms of
      exercise. Nevertheless, length, duration, intensity, mode, number of exercises,
      sets and repetitions varied markedly among studies. Supervised training sessions,
      recommended structured exercises, and splitting aerobic and resistance training
      in separate sessions may be relevant for best results. Future studies should
      analyze the effects of different aerobic and resistance training modes, different
      training and progression methods, and whether one type of exercise is optimal, as
      these issues are likely to convey greater knowledge on type 2 diabetes mellitus
      management through combined exercise.

PMID- 22981712
TI  - Allogeneic hematopoietic cell transplantation for MDS: for whom, when and how?
AB  - Hematopoietic cell transplantation (HCT) is currently the only treatment with
      curative potential for patients with myelodysplastic syndrome (MDS). However,
      treatment-related mortality and relapse have remained major barriers to uniform
      success. Therefore, important questions remain to be answered, such as whom to
      transplant, when and how. With reduced intensity conditioning (RIC) regimens,
      patients in their 70s and patients with comorbid conditions have been
      transplanted successfully, although the relapse incidence with this approach
      tends to be increased in comparison to high intensity regimens. Success rates are
      higher in patients transplanted at an early stage of their disease. Encouraging
      is the fact, that results with unrelated donors who are HLA-matched by high
      resolution typing are comparable to those achieved with HLA genotypically
      identical siblings. The establishment of cord blood as a source of stem cells,
      and the recent success with HLA-haploidentical related donors will allow the
      offering of HCT to virtually all patients. Dependent upon disease stage and
      characteristics, some 25% to 75% of transplanted patients will be cured. While
      20%-30% of patients experience chronic medical problems after HCT, 70% report a
      "good to excellent" quality of life. New studies must focus on further reducing
      GVHD for all patients and on overcoming high relapse rates in patients with high
      risk disease.

PMID- 22981713
TI  - The influence of reactive oxygen species on cell cycle progression in mammalian
      cells.
AB  - Cell cycle regulation is performed by cyclins and cyclin dependent kinases
      (CDKs). Recently, it has become clear that reactive oxygen species (ROS)
      influence the presence and activity of these enzymes and thereby control cell
      cycle progression. In this review, we first describe the discovery of enzymes
      specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery
      led to the recognition of ROS as essential players in many cellular processes,
      including cell cycle progression. ROS influence cell cycle progression in a
      context-dependent manner via phosphorylation and ubiquitination of CDKs and cell
      cycle regulatory molecules. We show that ROS often regulate ubiquitination via
      intermediate phosphorylation and that phosphorylation is thus the major
      regulatory mechanism influenced by ROS. In addition, ROS have recently been shown
      to be able to activate growth factor receptors. We will illustrate the diverse
      roles of ROS as mediators in cell cycle regulation by incorporating
      phosphorylation, ubiquitination and receptor activation in a model of cell cycle
      regulation involving EGF-receptor activation. We conclude that ROS can no longer
      be ignored when studying cell cycle progression.

PMID- 22981715
TI  - Measuring apparent trabecular density and bone structure using peripheral
      quantitative computed tomography at the tibia: precision in participants with and
      without spinal cord injury.
AB  - The objective of the study was to investigate the precision of standard outcomes
      obtained using peripheral quantitative computed tomography as well as apparent
      trabecular structure measures in adults with and without spinal cord injury
      (SCI). Twelve individuals with SCI, mean (standard deviation [SD]) 20 (13)yrs
      postinjury and mean (SD) age 44 (9)yrs, and 21 individuals without SCI (mean [SD]
      age: 27 [5]yrs) participated. Repeat scans of tibia epiphysis (4%) and shaft
      (66%) were performed using a Stratec XCT-2000 (Stratec Medizintechnik, Pforzheim,
      Germany). Bone mineral density and geometry variables (e.g., cortical thickness,
      bone area, polar moment of inertia) were derived with manufacturer's software.
      The following apparent trabecular structure variables were determined using
      custom software: average trabecular thickness (TrTh) (mm), trabecular spacing
      (TrSp) (mm), and trabecular number (TrN) (1/mm); average hole size (HA) and
      maximum hole size (HM) (mm(2)); connectivity index (CI); cortical thickness (CTh)
      (mm); bone volume to total volume (BVTV) ratio. Root mean square standard
      deviation and root mean square coefficient of variation (RMSCV; root mean square
      coefficient of variation percent [RMSCV%]) were calculated. The RMSCV% for all
      standard bone mineral density and geometry variables was <=2% except for total
      area (4% site), where precision was 3.8%. RMSCV% for bone structure variables
      were as follows: CTh 5.1, TrTh 1.7, TrN 1.9, TrSp 2.6, HA 9.5, HM 20.1, CI 5.1,
      and BVTV 1.4. Precision for bone density and geometry was excellent across a
      range of bone mineral densities. RMSCVs for some apparent trabecular structure
      variables were comparable to that of standard variables. The RMSCV for others may
      necessitate larger studies to detect between-group differences.

PMID- 22981714
TI  - Phosphatidic acid synthesis in bacteria.
AB  - Membrane phospholipid synthesis is a vital facet of bacterial physiology.
      Although the spectrum of phospholipid headgroup structures produced by bacteria
      is large, the key precursor to all of these molecules is phosphatidic acid
      (PtdOH). Glycerol-3-phosphate derived from the glycolysis via glycerol-phosphate
      synthase is the universal source for the glycerol backbone of PtdOH. There are
      two distinct families of enzymes responsible for the acylation of the 1-position
      of glycerol-3-phosphate. The PlsB acyltransferase was discovered in Escherichia
      coli, and homologs are present in many eukaryotes. This protein family primarily
      uses acyl-acyl carrier protein (ACP) endproducts of fatty acid synthesis as acyl
      donors, but may also use acyl-CoA derived from exogenous fatty acids. The second
      protein family, PlsY, is more widely distributed in bacteria and utilizes the
      unique acyl donor, acyl-phosphate, which is produced from acyl-ACP by the enzyme
      PlsX. The acylation of the 2-position is carried out by members of the PlsC
      protein family. All PlsCs use acyl-ACP as the acyl donor, although the PlsCs of
      the gamma-proteobacteria also may use acyl-CoA. Phospholipid headgroups are
      precursors in the biosynthesis of other membrane-associated molecules and the
      diacylglycerol product of these reactions is converted to PtdOH by one of two
      distinct families of lipid kinases. The central importance of the de novo and
      recycling pathways to PtdOH in cell physiology suggest that these enzymes are
      suitable targets for the development of antibacterial therapeutics in Gram
      positive pathogens. This article is part of a Special Issue entitled
      Phospholipids and Phospholipid Metabolism.

PMID- 22981716
TI  - Functional imaging of the thalamus in language.
AB  - Herein, the literature regarding functional imaging of the thalamus during
      language tasks is reviewed. Fifty studies met criteria for analysis. Two of the
      most common task paradigms associated with thalamic activation were generative
      tasks (e.g. word or sentence generation) and naming, though activation was also
      seen in tasks that involve lexical decision, reading and working memory.
      Typically, thalamic activation was seen bilaterally, left greater than right,
      along with activation in frontal and temporal cortical regions. Thalamic
      activation was seen with perceptually challenging tasks, though few studies
      rigorously correlated thalamic activation with measures of attention or task
      difficulty. The peaks of activation loci were seen in virtually all thalamic
      regions, with a bias towards left-sided and midline activation. These analyses
      suggest that the thalamus may be involved in processes that involve manipulations
      of lexical information, but point to the need for more systematic study of the
      thalamus using language tasks.

PMID- 22981717
TI  - Behavior in the open field predicts the number of KCl-induced cortical spreading
      depressions in rats.
AB  - Anxiety disorders are known to be comorbid with migraine, and cortical spreading
      depression (CSD) is the most likely cause of the migraine aura. To search for
      possible correlations between susceptibility to CSD and anxiety we used the open
      field test in male Sprague-Dawley rats chronically treated with the preventive
      anti-migraine drugs valproate or riboflavin. Animals avoiding the central area of
      the open field chamber and those with less exploratory activity (i.e. rearing)
      were considered more anxious. After 4 weeks of treatment CSDs were elicited by
      application of 1M KCl over the occipital cortex and the number of CSDs occurring
      over a 2h period was compared to the previously assessed open field behavior.
      Higher anxiety-like behavior was significantly correlated with a higher frequency
      of KCl-induced CSDs. In saline-treated animals, fewer rearings were found in
      animals with more frequent CSDs (R=-1.00). The duration of ambulatory episodes in
      the open field center correlated negatively with number of CSDs in the valproate
      group (R=-0.83; p<0.005) and in riboflavin treated group (R=-0.69; p<0.05) as
      well as total time spent in the open field center in both groups (R=-0.75; p<0.05
      and R=-0.58; p<0.1 respectively). These results suggest that anxiety symptoms are
      associated with susceptibility to CSD and might explain why it can be an
      aggravating factor in migraine with aura.

PMID- 22981718
TI  - Biochemistry detection of acetylcholinesterase activity in Trypanosoma evansi and
      possible functional correlations.
AB  - Several chemical and immunohistochemical techniques can be used for the detection
      of acetylcholinesterase (AChE) activity. In this experiment we aimed to detect
      AChE activity in Trypanosoma evansi. For this, the parasites were isolated from
      the blood of experimentally infected rats using a DEA-cellulose column. Enzymatic
      activity was determined in trypomastigote forms at 0, 0.2, 0.4, 0.8 and 1.2 mg/mL
      of protein concentrations by a standard biochemical protocol. At all
      concentrations tested, the study showed that T. evansi expresses the enzyme AChE
      and its activity was proportional to the concentration of protein, ranging
      between 0.64 and 2.70 MUmol of AcSCh/h. Therefore, we concluded that it is
      possible to biochemically detect AChE in T. evansi, an enzyme that may be
      associated with vital functions of the parasite and also can be related to
      chemotherapy treatments, as further discussed in this article.

PMID- 22981719
TI  - Leishmanicidal activity of an alkenylphenol from Piper malacophyllum is related
      to plasma membrane disruption.
AB  - Leishmaniasis and Chagas disease are parasitic protozoan infections that affect
      the poorest population in the world, causing high mortality and morbidity. As a
      result of highly toxic and long-duration treatments, novel, safe and more
      efficacious drugs are essential. In this work, the methanol (MeOH) extract from
      the leaves of Piper malacophyllum (Piperaceae) was fractioned to afford one
      alkenylphenol, which was characterized as 4-[(3'E)-decenyl]phenol (gibbilimbol B)
      by spectroscopic methods. Anti-protozoan in vitro assays demonstrated for the
      first time that Leishmania (L.) infantum chagasi was susceptible to gibbilimbol
      B, with an in vitro EC(50) of 23 MUg/mL against axenic promastigotes and an
      EC(50) of 22 MUg/mL against intracellular amastigotes. Gibbilimbol B was also
      tested for anti-trypanosomal activity (Trypanosoma cruzi) and showed an EC(50)
      value of 17 MUg/mL against trypomastigotes. To evaluate the cytotoxic parameters,
      this alkenylphenol was tested in vitro against NCTC cells, showing a CC(50) of 59
      MUg/mL and absent hemolytic activity at the highest concentration of 75 MUg/mL.
      Using the fluorescent probe SYTOX Green suggested that the alkenylphenol
      disrupted the Leishmania plasma membrane upon initial incubation. Further drug
      design studies aiming at derivatives could be a promising tool for the
      development of new therapeutic agents for leishmaniasis and Chagas disease.

PMID- 22981720
TI  - Preferential growth of skeletal myoblasts and fibroblasts in co-culture on a
      dendrimer-immobilized surface.
AB  - Co-culture of human skeletal muscle myoblasts and fibroblasts was performed on a
      dendrimer-immobilized surface. Morphological changes by cytoskeletal variation
      were observed, compared with culture on a conventional tissue culture surface,
      and preferential growth of myoblasts can be achieved by inhibition of fibroblast
      growth.

PMID- 22981721
TI  - The effectiveness of a single-stage versus traditional three-staged protocol of
      hospital disinfection at eradicating vancomycin-resistant Enterococci from
      frequently touched surfaces.
AB  - BACKGROUND: Environmental contamination is a reservoir for vancomycin-resistant
      enterococcus (VRE) in hospitals. METHODS: Environmental sampling of surfaces was
      undertaken anytime before disinfection and 1 hour after disinfection utilizing a
      sodium dichloroisocyanurate-based, 3-staged protocol (phase 1) or benzalkonium
      chloride-based, single-stage clean (phase 2). VRE colonization and infection
      rates are presented from 2010 to 2011, and audits of cleaning completeness were
      also analyzed. RESULTS: Environmental samples collected before disinfection were
      significantly more likely to be contaminated with VRE during phase 1 than phase
      2: 25.2% versus 4.6%, respectively; odds ratio (OR), 7.01 (P < .01).
      Environmental samples collected after disinfection were also significantly more
      likely to yield VRE during phase 1 compared with phase 2: 11.2% versus 1.1%,
      respectively; OR, 11.73 (P < .01). Rates of VRE colonization were higher during
      2010 than 2011. Cleaning audits showed similar results over both time periods.
      CONCLUSION: During use of a chlorine-based, 3-staged protocol, significantly
      higher residual levels of VRE contamination were identified, compared with levels
      detected during use of a benzalkonium chloride-based product for disinfection.
      This reduction in VRE may be due to a new disinfection product, more attention to
      the thoroughness of cleaning, or other supplementary efforts in our institution.

PMID- 22981722
TI  - Antiurolithiatic activity of saponin rich fraction from the fruits of Solanum
      xanthocarpum Schrad. & Wendl. (Solanaceae) against ethylene glycol induced
      urolithiasis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A well-known traditional herb Solanum
      xanthocarpum is widely used in India for the management of different ailments
      including urolithiasis. This study was designed to rationalize the use of Solanum
      xanthocarpum in kidney stone and to investigate its mechanism of action.
      MATERIALS AND METHODS: The saponin rich fraction prepared from fruits of Solanum
      xanthocarpum (SXS) was evaluated for antiurolithiatic activity by in vitro and in
      vivo studies. In ethylene glycol (EG, 0.75% in drinking water for 28 days)
      induced urolithiasis model, two different experimental doses (20 mg/kg and 40
      mg/kg, p.o., for 28 days) of saponin rich fraction were selected by dose fixation
      study. After 28 days, various biochemical parameters were measured in urine,
      serum and kidney homogenate. Kidneys were also subjected to histopathological
      analysis. RESULTS: In vitro calcium oxalate crystal (CaOx) nucleation as well as
      aggregation was inhibited in artificial urine solution by SXS. The lithogenic
      treatment caused polyuria, damage renal function and oxidative stress, manifested
      as increased malondialdehyde, depleted reduced glutathione and decreased
      antioxidant enzyme catalase activities of the kidneys, which were prevented by
      simultaneous administration with SXS. Lithogenic treatment also caused
      crystalluria, hyperoxaluria, hypercalciuria, hypocitrauria, and hypomagnesaemia.
      Deposition of CaOx in renal tissue and cellular injury were seen in
      histopathology. Co-administration of SXS had potential to prevent these
      pathological changes due to lithogenic treatment. Moreover, SXS raised level of
      glycosaminoglycan, a stone inhibitor macromolecule found in urine which
      decreased. CONCLUSION: The antiurolithiatic activity in Solanum xanthocarpum is
      mediated possibly through the inhibition of CaOx crystal formation and its effect
      on the urinary concentration of stone-forming constituents and nephrolithiasis
      inducing factors and this study rationalizes its medicinal use in urolithiasis.

PMID- 22981723
TI  - Inhibitory activity of Dodonaea viscosa var. angustifolia extract against
      Streptococcus mutans and its biofilm.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Dodonaea viscosa var. angustifolia
      (DVA) are traditionally used for the treatment of fever, colds, oral thrush,
      toothaches and related problems. Streptococcus mutans is implicated in many oral
      infections. This study investigated the inhibitory activity of DVA extract
      against Streptococcus mutans and its biofilm. MATERIALS AND METHODS: Crude
      extract of the leaves was prepared using methanol. The time-kill curve for
      Streptococcus mutans at different concentrations of methanol extract after 6 and
      24 h was determined. Biofilms of Streptococcus mutans were grown in the presence
      of subinhibitory concentration of extract (0.78 mg/ml) for 30 h and the bacterial
      counts were obtained after 6, 24 and 30 h. The chemical profile of the crude
      extract was obtained using gas chromatography-mass spectrometry (GC-MS). RESULTS:
      The reduction of Streptococcus mutans was concentration and exposure time
      dependent. The crude extract killed 48% of S. mutans at a lowest concentration of
      0.1 mg/ml and 100% at 25 mg/ml after 6h. Biofilm formation was reduced by 95, 97
      and 99% after 6, 24 and 30 h of exposure to the subinhibitory concentration of
      crude extract respectively. GC-MS analyses revealed the presence of polyphenols
      such as catechin or chromene groups, chalcones with trimethoxyphenyl group and
      tannin with 4-O-beta-D-xylopyranoside. At high concentration the crude extract
      was bactericidal to Streptococcus mutans but subinhibitory concentration
      significantly reduced the planktonic cells and biofilm formation. CONCLUSIONS:
      These results suggest that this plant has the potential to be used to control S.
      mutans and its biofilm which are responsible for oral infections.

PMID- 22981724
TI  - Effect of decursin on the pharmacokinetics of theophylline and its metabolites in
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Decursin is used as a traditional Asian medicine
      to treat various women's diseases. AIM OF THE STUDY: Herb-drug interaction has
      become a serious problem since herbal medicine is extensively used in the modern
      world. This study investigates effects of decursin, on the pharmacokinetics of
      theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats.
      MATERIALS AND METHODS: After decursin pretreatment for 3 days, on the fourth day
      rats were administered decursin and theophylline concomitantly. The blood
      theophylline and its major metabolites (1-methylxanthine (1-MX), 3-methylxanthine
      (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (1,3-DMU)) levels
      were monitored with LC-MS/MS. RESULTS: The results indicated that the clearance,
      elimination rate constant (K(el)) of theophylline was significantly decreased and
      area under concentration-time curve (AUC), C(max), half-life was increased in
      decursin (25mg/kg) pretreatment when theophylline (10mg/kg) was given. In the
      presence of decursin, the pharmacokinetic parameters of three metabolites (1-MX,
      1,3-DMU, and 1-MU) were affected and the differences were statistically
      significant about AUC(24)(h) parameter. CONCLUSION: Our results suggest that
      patients who want to use CYP1A2-metabolized drugs such as caffeine and
      theophylline should be advised of the potential herb-drug interaction, to reduce
      therapeutic failure or increased toxicity of conventional drug therapy.

PMID- 22981725
TI  - The binding of resveratrol to monomer and fibril amyloid beta.
AB  - As currently understood, Alzheimer's disease (AD) is a chronic neurodegenerative
      disorder that is driven by the aggregation of amyloid beta (Abeta) protein. It
      has been shown that resveratrol (RES) may attenuate amyloid beta peptide-induced
      toxicity, promote Abeta clearance and reduce senile plaques. However, it remains
      to be determined whether RES could interact directly with Abeta. The aim of the
      present study was to examine the direct binding of RES to monomer and fibril
      Abeta. Using surface plasmon resonance (SPR) and proton nuclear magnetic
      resonance ((1)H NMR), our results identified the direct binding of RES to Abeta.
      The ability of RES to bind to both fibril and monomer Abeta(1-40 and 1-42) was
      further analyzed by SPR. The binding response of RES to fAbeta(1-42) was higher
      than that to monomer Abeta(1-42), whereas the binding response of RES to fAbeta(1
      40) was lower than that to monomer Abeta(1-40). The K(D) of RES for fibril
      Abeta(1-40 or 1-42) was higher than that for the corresponding monomer Abeta.
      Compared to the control compound Congo red (CR), the binding responses of RES to
      monomer Abeta(1-42) and Abeta(1-40) were stronger, but binding to fibril Abeta(1
      42) was weaker, and the K(D)s of RES with both monomer and fibril Abeta(1-40) and
      Abeta(1-42) were higher than that of CR. When Abeta(1-40 or 1-42) was co
      incubated with RES (50MUM), the thioflavin T fluorescence of the mixture was
      weakened, and the number and length of amyloid fibrils were decreased.
      Furthermore, the results of staining in consecutive brain slices from AD patients
      showed that RES (10(-4)M) could stain senile plaques. These results indicated
      that RES could bind directly to Abeta in different states, which may provide new
      insight into the protective properties of RES against AD.

PMID- 22981726
TI  - Characterizing hepatocellular carcinoma using multi-breath-hold two-dimensional
      susceptibility-weighted imaging: comparison to conventional liver MRI.
AB  - AIM: To characterize the imaging manifestations of hepatocellular carcinoma (HCC)
      using multi-breath-hold two-dimensional susceptibility-weighted imaging (SWI) and
      compare to conventional liver magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: Forty-three patients with histopathologically confirmed HCC underwent
      conventional liver MRI, multi-breath-hold two-dimensional SWI, and contrast
      enhanced CT preoperatively. The T1-weighted imaging (WI), T2WI, and SWI images
      were evaluated in consensus by two experienced radiologists. The tumour
      boundaries, blood products in the tumour, venous vessels, and non-tumour liver
      parenchyma were compared. RESULTS: SWI demonstrated significantly better tumour
      boundary detection than T1WI and T2WI imaging (67.4 and 25.6%, respectively). The
      detection rate for intra-tumoural blood products using SWI was higher than that
      of T1WI and T2WI (76.7 and 16.3%, respectively). The detection rate for tumour
      venous vessels using SWI was 72.1%, while none was detected with conventional
      T1WI and T2WI. The detection rate for siderotic nodules in non-tumour liver
      parenchyma using SWI was higher than that of conventional T1WI and T2WI (65.1 and
      20.9%, respectively). CONCLUSIONS: SWI can provide more detailed information than
      conventional liver MRI in evaluation of tumour boundaries, blood products, venous
      vasculature, and non-tumour liver parenchyma. SWI is a valuable complement to
      conventional liver MRI.

PMID- 22981727
TI  - Prognostic significance of 18-FDG PET/CT and EUS-defined tumour characteristics
      in patients with oesophageal cancer.
AB  - AIM: To determine the correlation between 2-[(18)F]-fluoro-2-deoxy-d-glucose
      (FDG) positron-emission tomography/computed tomography (PET/CT) defined maximum
      standardized uptake value (SUVmax) and endoluminal ultrasound-defined tumour
      volume (EDTV) in patients with oesophageal cancer (OC) and their relative
      prognostic significance. MATERIALS AND METHODS: One hundred and eighty-five
      consecutive patients with OC were staged using CT, endoscopic ultrasound (EUS),
      and PET/CT. The maximum potential EDTV was calculated (pir(2)L, where r = tumour
      thickness and L = total length of disease including proximal and distal lymph
      node metastases). Primary outcome measure was survival from diagnosis. RESULTS:
      Ninety-one percent of patients (168/185) had FDG-avid tumours on PET/CT. SUVmax
      correlated positively and significantly with EDTV (Spearman's rho = 0.339, p =
      0.001). On univariate analysis, survival was inversely related to the PET/CT
      lymph node metastasis count (LNMC, p = 0.015), EUS N stage (p = 0.002), EDTV (<48
      cm(3), p = 0.001), EUS total length of disease (p = 0.001), SUVmax (p = 0.002),
      PET/CT N stage (p < 0.0001), and EUS LNMC (p < 0.0001). On multivariate analysis
      two factors were significantly and independently associated with survival: EDTV
      (HR, 3.118; 95% CI: 1.357-7.167; p = 0.007), and PET/CT N stage (HR, 0.496; 95%
      CI: 0.084-1.577; p = 0.022). CONCLUSION: EDTV and PET/CT N stage were important
      predictors of survival and further research is needed to identify critical
      prognostic values.

PMID- 22981728
TI  - Diffusion-weighted MRI of the liver-Interpretative pearls and pitfalls.
AB  - Diffusion-weighted magnetic resonance imaging (DW MRI) is an established
      technique in neuroradiology and more recently has emerged as a useful adjunct to
      various oncological applications of MRI. It has an expanding role in the
      evaluation of liver lesions, offers higher detection rates for small lesions, and
      can increase confidence in differentiating between benign and malignant lesions.
      Other applications include assessment of tumour response to therapy,
      differentiating tumour from bland thrombus, and assessment of liver fibrosis. DW
      sequences can be performed on most modern MRI machines with relative ease, in a
      short time period and without the need for contrast medium. DW MRI can be of
      value in the detection and characterization of hepatic lesions but there are
      pitfalls, which can potentially cause interpretative difficulty. This article
      will review the rationale for DW MRI in liver imaging, demonstrate the clinical
      utility of the technique in a spectrum of hepatic diseases, and illustrate key
      interpretative pearls and pitfalls.

PMID- 22981729
TI  - Impact of delay after biopsy and post-biopsy haemorrhage on prostate cancer
      tumour detection using multi-parametric MRI: a multi-reader study.
AB  - AIM: To assess impact of haemorrhage and delay after biopsy on prostate tumour
      detection using multi-parametric (MP) magnetic resonance imaging (MRI)
      assessment. MATERIALS AND METHODS: Forty-four patients underwent prostate MRI at
      1.5 T using a pelvic phased-array coil, including T1-weighted imaging (T1WI), T2
      weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast
      enhanced (DCE) imaging, before prostatectomy. Three radiologists independently
      reviewed images during four sessions [T2WI, DWI, DCE, and all parameters combined
      (MP-MRI)] to assess for tumour in each sextant. In a separate session, readers
      reviewed T1WI to score the extent of haemorrhage per sextant. Accuracy was
      assessed using logistic regression for correlated data. RESULTS: There was no
      significant difference in accuracy between readers for any session (p >= 0.166),
      and results were averaged across the three readers for remaining comparisons.
      Accuracy was significantly greater for MP-MRI than for any parameter alone (p <=
      0.020). For T2WI alone, there was a trend toward decreased sensitivity in
      sextants with extensive haemorrhage (p = 0.072). However, accuracy, sensitivity,
      and specificity were otherwise similar for sextants with and without extensive
      haemorrhage for all sessions (p = 0.192-0.934). No session showed a significant
      improvement in accuracy, sensitivity, or specificity in cases with delay after
      biopsy of over 4 weeks compared with shorter delay. CONCLUSION: Extensive
      haemorrhage and short delay after biopsy did not negatively impact accuracy for
      tumour detection using MP-MRI. Further studies using MP-MRI protocols and
      interpretation schemes from other institutions are required to confirm these
      observations.

PMID- 22981730
TI  - CO2 microbubble contrast enhancement in x-ray angiography.
AB  - AIM: To demonstrate that carbon dioxide (CO2) microbubble contrast enhancement
      depicts blood vessels when used for x-ray examinations. MATERIALS AND METHODS:
      Microbubbles were generated by cavitation of physiological saline to which CO2
      gas had been added using an ejector-type microbubble generator. The input
      pressure values for CO2 gas and physiological saline that produced a large
      quantity of CO2 microbubbles were obtained in a phantom. In an animal study,
      angiography was performed in three swine using three types of contrast: CO2
      microbubbles, conventional CO2 gas, and iodinated contrast medium. For CO2
      microbubble contrast enhancement, physiological saline, and CO2 gas were supplied
      at the input pressures calculated in the phantom experiment. Regions of interest
      were set in the abdominal aorta, external iliac arteries, and background. The
      difference in digital values between each artery and the background was
      calculated. RESULTS: The input pressures obtained in the phantom experiment were
      0.16 MPa for physiological saline and 0.5 MPa for CO2 gas, with physiological
      saline input volume being 8.1 ml/s. Three interventional radiologists all
      evaluated the depictions of all arteries as "present" in the CO2 microbubble
      contrast enhancement, conventional CO2 contrast enhancement, and iodinated
      contrast enhancement performed in three swine. Digital values for all vessels
      with microbubble CO2 contrast enhancement were higher than background values.
      CONCLUSIONS: In x-ray angiography, blood vessels can be depicted by CO2
      microbubble contrast enhancement, in which a large quantity of CO2 microbubbles
      is generated within blood vessels.

PMID- 22981731
TI  - CT coronary angiography: image quality with sinogram-affirmed iterative
      reconstruction compared with filtered back-projection.
AB  - AIM: To investigate image quality and potential for radiation dose reduction
      using sinogram-affirmed iterative reconstruction (SAFIRE) at computed tomography
      (CT) coronary angiography (CTCA) compared with filtered back-projection (FBP)
      reconstruction. MATERIALS AND METHODS: A water phantom and 49 consecutive
      patients were scanned using a retrospectively electrocardiography (ECG)-gated
      CTCA protocol on a dual-source CT system. Image reconstructions were performed
      with both conventional FBP and SAFIRE. The SAFIRE series were reconstructed image
      data from only one tube, simulating a 50% radiation dose reduction. Two blinded
      observers independently assessed the image quality of each coronary segment using
      a four-point scale and measured image noise (the standard deviation of Hounsfield
      values, SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR).
      Radiation dose estimates were calculated. RESULTS: In the water phantom, image
      noise decreased at the same ratio as the tube current increased for both
      reconstruction algorithms. Despite an estimated radiation dose reduction from 7.9
      +/- 2.8 to 4 +/- 1.4 mSv, there was no significant difference in the SD and SNR
      within the aortic root and left ventricular chamber between the two
      reconstruction methods. There was also no significant difference in the image
      quality between the FBP and SAFIRE series. CONCLUSION: Compared with traditional
      FBP, there is potential for substantial radiation dose reduction at CTCA with use
      of SAFIRE, while maintaining similar diagnostic image quality.

PMID- 22981732
TI  - Heterogeneity of risk within racial groups, a challenge for public health
      programs.
AB  - Targeting high-risk populations for public health interventions is a classic tool
      of public health promotion programs. This practice becomes thornier when racial
      groups are identified as the at-risk populations. I present the particular
      ethical and epistemic challenges that arise when there are low-risk
      subpopulations within racial groups that have been identified as high-risk for a
      particular health concern. I focus on two examples. The black immigrant
      population does not have the same hypertension risk as US-born African Americans.
      Similarly, Finnish descendants have a far lower rate of cystic fibrosis than
      other Caucasians. In both cases the exceptional nature of these subpopulations
      has been largely ignored by the designers of important public health efforts,
      including the recent US government dietary recommendations. I argue that amending
      the publicly-disseminated risk information to acknowledge these exceptions would
      be desirable for several reasons. First, recognizing low-risk subpopulations
      would allow more efficient use of limited resources. Communicating this valuable
      information to the subpopulations would also promote truth-telling. Finally,
      presenting a more nuanced empirically-supported representation of which groups
      are at known risk of diseases (not focusing on mere racial categories) would
      combat harmful biological race essentialist views held by the public.

PMID- 22981733
TI  - Relationship between physical activity and general mental health.
AB  - PURPOSE: We investigated the relationship between physical activity and mental
      health and determined the optimal amount of physical activity associated with
      better mental health. METHOD: Self-reported data from a national random sample of
      7674 adult respondents collected during the 2008 U.S. Health Information National
      Trends 2007 Survey (HINTS) were analyzed in 2012. Mental health was plotted
      against the number of hours of physical activity per week using a fractional 2
      degree polynomial function. Demographic and physical health factors related to
      poorer mental health were examined. The optimal range of physical activity
      associated with poorer mental health was examined by age, gender, and physical
      health. RESULTS: A curvilinear association was observed between physical activity
      and general mental health. The optimal threshold volume for mental health
      benefits was of 2.5 to 7.5h of weekly physical activity. The associations varied
      by gender, age, and physical health status. Individuals who engaged in the
      optimal amount of physical activity were more likely to have reported better
      mental health (odds ratio=1.39, p=0.006). CONCLUSIONS: This study established a
      hyperbolic dose-response relationship between physical activity and general
      mental health, with an optimal range of 2.5 to 7.5h of physical activity per
      week.

PMID- 22981734
TI  - Native type IV collagen induces an epithelial to mesenchymal transition-like
      process in mammary epithelial cells MCF10A.
AB  - Basement membrane (BM) is a complex network of interacting proteins, including
      type IV collagen (Col IV) that acts as a scaffold that stabilizes the physical
      structures of tissues and regulates cellular processes. In the mammary gland, BM
      is a continuous deposit that separates epithelial cells from stroma, and its
      degradation is related with an increased potential for invasion and metastasis.
      Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells
      are transdifferentiated to one mesenchymal state, and is a normal process during
      embryonic development, tissue remodeling and wound healing, as well as it has
      been implicated during cancer progression. In breast cancer cells, native Col IV
      induces migration and gelatinases secretion. However, the role of native Col IV
      on the EMT process in human mammary epithelial cells remains to be investigated.
      In the present study, we demonstrate that native Col IV induces down-regulation
      of E-cadherin expression, accompanied with an increase of Snail1, Snail2 and Sip1
      transcripts. Native Col IV also induces an increase in N-cadherin and vimentin
      expression, an increase of MMP-2 secretion, the activation of FAK and NFkappaB,
      cell migration and invasion in MCF10A cells. In summary, these findings
      demonstrate, for the first time, that native Col IV induces an EMT-like process
      in MCF10A human mammary non-tumorigenic epithelial cells.

PMID- 22981735
TI  - Variation in foot conformation in lame horses with different foot lesions.
AB  - Foot conformation in the horse is commonly thought to be associated with lameness
      but scientific evidence is scarce although it has been shown in biomechanical
      studies that foot conformation does influence the forces acting on the deep
      digital flexor tendon (DDFT) and the navicular bone (NB). The aim of this study
      was to determine the relationships between foot conformation and different types
      of lesion within the foot in lame horses. It was hypothesised that certain
      conformation parameters differ significantly between different types of foot
      lesions. Conformation parameters were measured on magnetic resonance images in
      the mid-sagittal plane of 179 lame horses with lesions of their deep digital
      flexor tendon (DDFT), navicular bone (NB), collateral ligaments of the distal
      interphalangeal joints and other structures. Conformation parameters differed
      significantly between lesion groups. A larger sole angle was associated with
      combined DDFT and NB lesions, but not with NB lesions alone. A more acute angle
      of the DDFT round the NB was associated with DDFT and NB lesions, and a lower
      heel height index with DDFT injury. The larger the sole angle the smaller the
      likelihood of a DDFT or NB lesion with odds ratios of 0.86 and 0.90,
      respectively. This study shows an association between foot conformation and
      lesions but it does not allow the identification of conformation as causative
      factor since foot conformation may change as a consequence of lameness. Future
      studies will investigate foot-surface interaction in lame vs. sound horses, which
      may open a preventative and/or therapeutic window in foot lame horses.

PMID- 22981736
TI  - Sensitivity and specificity of a hand-held milk electrical conductivity meter
      compared to the California mastitis test for mastitis in dairy cattle.
AB  - Screening tests for mastitis can play an important role in proactive mastitis
      control programs. The primary objective of this study was to compare the
      sensitivity and specificity of milk electrical conductivity (EC) to the
      California mastitis test (CMT) in commercial dairy cattle in South Africa using
      Bayesian methods without a perfect reference test. A total of 1848 quarter milk
      specimens were collected from 173 cows sampled during six sequential farm visits.
      Of these samples, 25.8% yielded pathogenic bacterial isolates. The most
      frequently isolated species were coagulase negative Staphylococci (n=346),
      Streptococcus agalactiae (n=54), and Staphylococcus aureus (n=42). The overall
      cow-level prevalence of mastitis was 54% based on the Bayesian latent class (BLC)
      analysis. The CMT was more accurate than EC for classification of cows having
      somatic cell counts >200,000/mL and for isolation of a bacterial pathogen. BLC
      analysis also suggested an overall benefit of CMT over EC but the statistical
      evidence was not strong (P=0.257). The Bayesian model estimated the sensitivity
      and specificity of EC (measured via resistance) at a cut-point of >25 mOmega/cm
      to be 89.9% and 86.8%, respectively. The CMT had a sensitivity and specificity of
      94.5% and 77.7%, respectively, when evaluated at the weak positive cut-point. EC
      was useful for identifying milk specimens harbouring pathogens but was not able
      to differentiate among evaluated bacterial isolates. Screening tests can be used
      to improve udder health as part of a proactive management plan.

PMID- 22981737
TI  - Specific binding of collagen Q to the neuromuscular junction is exploited to cure
      congenital myasthenia and to explore bases of myasthenia gravis.
AB  - Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to
      the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of
      asymmetric AChE (AChE/ColQ). The C-terminal domain of ColQ binds to MuSK, the
      muscle-specific receptor tyrosine kinase, that mediates a signal for
      acetylcholine receptor (AChR) clustering at the NMJ. ColQ also binds to heparan
      sulfate proteoglycans including perlecan. Congenital defects of ColQ cause
      endplate AChE deficiency. A single intravenous administration of adeno-associated
      virus serotype 8 (AAV8)-COLQ to Colq-/- mice rescued motor functions, synaptic
      transmission, and the ultrastructure of NMJ. We also injected AAV1-COLQ-IRES-EGFP
      to the left tibialis anterior and observed colocalization of AChE/ColQ at all the
      examined NMJs of the non-injected limbs. Additionally, injection of purified
      recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in
      non-injected forelimbs. These observations suggest that the tissue-targeting
      signal of ColQ can be exploited to specifically deliver the transgene product to
      the target tissue. MuSK antibody-positive myasthenia gravis (MG) accounts for 5
      15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase
      inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if
      the patient's MuSK-IgG interferes with binding of ColQ to MuSK. In vitro overlay
      of AChE/ColQ to muscle sections of Colq-/- mice revealed that MuSK-IgG blocks
      binding of ColQ to the NMJ. In vitro plate-binding of MuSK to ColQ disclosed that
      MuSK-IgG exerts a dose-dependent block of MuSK-ColQ interaction. In addition,
      passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ~10%
      of controls and had a lesser effect on the sizes and densities of AChR and MuSK.
      Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ
      enabled us to ameliorate devastating myasthenic symptoms of Colq-/- mice and to
      reveal bases of anti-MuSK MG.

PMID- 22981738
TI  - Association between common risk factors and molecular subtypes in breast cancer
      patients.
AB  - BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women
      worldwide and characterized its by molecular and clinical heterogeneity. Gene
      expression profiling studies have classified breast cancers into five subtypes:
      luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like.
      Although clinical differences between subtypes have been well described in the
      literature, etiologic heterogeneity have not been fully studied. The aim of this
      study was to assess the associations between several hormonal and nonhormonal
      risk factors and molecular subtypes of breast cancer. METHODS: This cross
      sectional study consisted of 1884 invasive breast cancer cases. Variables studied
      included family history, age at first full-term pregnancy, number of children,
      duration of lactation, menstruation history, menopausal status, blood type,
      smoking, obesity, oral contraceptive use, hormone replacement therapy and in
      vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were
      estimated using multivariate logistic regression analysis. RESULTS: Thousand two
      hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2
      overexpressing and 232 had triple negative breast cancer. The age of >=40 years
      was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15-1.74; p=0.001)
      and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01-2.25; p=0.04). Women who
      were nulliparous (OR 1.48, 95% CI 1.03-2.13; p=0.03) or who had their first full
      term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83-1.88; p=0.04) were
      at increased risk of luminal breast cancer, whereas women with more than two
      children had a decreased risk (OR 0.68, 95% CI 0.47-0.97; p=0.03). Breast-feeding
      was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53-1.04;
      p=0.04) when compared to non-luminal breast cancer. We found increased risks for
      postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93-5.17;
      p=0.04) and luminal A (OR 1.87, 95% CI 0.93-3.90, p=0.02) breast cancers, who
      used hormone replacement therapy for 5 years or more. Overweight and obesity
      significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06
      3.37; p=0.04 and OR 1.90 95% CI 1.00-3.61; p=0.03), on the contrary, decreased
      the risk of luminal breast cancer (OR 0.63 95% CI 0.43-0.95; p=0.02 and OR 0.50
      95% CI 0.32-0.76; p=0.002, respectively) in premenopausal women. There were no
      significant differences between risk of breast cancer subtypes and early
      menarche, late menopause, family history, postmenopausal obesity, oral
      contraseptive use, smoking, in vitro fertilization, blood groups and use of
      hands. CONCLUSIONS: Reproductive and hormonal characteristics (breastfeeding,
      parity, age at first full-term birth, hormone replacement therapy) were
      associated with luminal subtype, compared to non-luminal breast cancer, as
      consistent with previous studies. Obesity and overweight increased the risk of
      triple negative subtype, particularly in premenopausal women. Older age and use
      of hormone replacement therapy were related to the risk of HER-2 overexpressing
      breast cancer. Our data suggest a significant heterogeneity in association of
      traditional breast cancer risk factors and tumor subtypes.

PMID- 22981739
TI  - Regulation of adhesion site dynamics by integrin traffic.
AB  - The dynamic control of integrin-mediated cell adhesion to extracellular matrix
      proteins is crucial for several physiological and pathological phenomena as
      diverse as embryonic morphogenesis, muscle contraction, tissue repair, and cancer
      cell dissemination. On one hand, the intrinsic conformational plasticity of
      integrins, which can be bidirectionally modulated by their ligands and cytosolic
      adaptors in combination with physical forces, is a key regulatory parameter. On
      the other hand, endo-exocytic integrin traffic logistics represent an additional
      important mode of control. Herein, we highlight how these two apparently parallel
      and independent strategies for tuning integrin function appear instead to be
      indissolubly intermingled, as eukaryotic cells have evolved distinct molecular
      strategies and endosomal pathways to traffic ligand-bound and ligand-free
      integrins.

PMID- 22981740
TI  - Commentary on: "Temporary rapid bowel ligation as a damage control adjunct".

PMID- 22981741
TI  - The effects of PPAR-gamma agonist pioglitazone on renal ischemia/reperfusion
      injury in rats.
AB  - BACKGROUND: Acute renal failure due to renal ischemia/reperfusion (IR) injury is
      a significant clinical problem in cardiovascular surgery. Reactive oxygen species
      and inflammation play essential roles in the pathophysiology of IR injury. Matrix
      metalloproteinases (MMPs) are enzymes that play important roles in inflammation
      and mediate extracellular matrix degradation. It is known that peroxisome
      proliferator-activated receptor-gamma agonists have antiinflammatory and
      antioxidant effects. In the present study, we aimed to investigate the effects of
      pioglitazone, a synthetic peroxisome proliferator-activated receptor-gamma
      agonist, on MMPs and oxidative stress in a renal IR injury model in rats.
      MATERIALS AND METHODS: Male Wistar albino rats were divided into three groups:
      control (n = 7), placebo (n = 7; saline/p.o.), and pioglitazone (n = 7; 5
      mg/kg/day/p.o.). In the control group, a right nephrectomy was conducted without
      left renal IR injury. In the placebo and pioglitazone groups, pretreatments were
      started 3 d before operation. In both groups, left renal pedicles were clamped
      for 60 min and then reperfused for 60 min. Paraffinized renal sections were
      evaluated histopathologically. Furthermore, expressions of MMP-2, MMP-9, tissue
      inhibitor of metalloproteinase (TIMP)-2, superoxide dismutase 1 (SOD1), and p47
      phox/p67-phox subunits of NADPH oxidase were determined by immunostaining and
      scoring. RESULTS: In the placebo group, renal IR injury induced diffuse tubular
      necrosis and intense acute inflammation, but pioglitazone inhibited these
      effects. MMP-2, MMP-9, and TIMP-2 expression increased in the placebo group.
      However, while MMP-2 and -9 expression decreased, TIMP-2 expression did not
      change in the pioglitazone group. p47-phox/p67-phox expression increased in the
      placebo group, but SOD1 expression did not change. Pioglitazone diminished p47
      phox/p67-phox expression, whereas it enhanced SOD1 expression. CONCLUSION: Our
      results suggest that pioglitazone might be helpful to reduce renal IR injury
      because of its antiinflammatory and antioxidant effects.

PMID- 22981742
TI  - Effects of Mg2+ on the bivalent mercury reduction behaviors in simulated wet FGD
      absorbents.
AB  - This paper studied the bivalent mercury reduction behaviors after Mg(2+) addition
      in the simulated Ca-based and Dual-Alkali flue gas desulfurization (FGD)
      absorbents. Experimental results showed that the reduction of bivalent mercury
      was increased in the Ca-based FGD absorbent and inhibited in the Dual-Alkali FGD
      absorbent. It was proposed that the former was mainly attributed to the enhanced
      dissolution and recrystallization of CaSO(3) particles by Mg(2+) addition, which
      provided more active surface for mercury adsorption and reduction, whilst the
      latter was mainly due to the formation of neutral MgSO(3)(0) ion pair, which
      tended to lower the active sulfite concentration in the simulated solution.

PMID- 22981743
TI  - A method of identifying priority spatial patterns for the management of potential
      ecological risks posed by heavy metals.
AB  - An approach of identifying priority spatial patterns in response to different
      ecological risk levels associated with heavy metals (HM) is proposed. First,
      ecological hotspots (EH) are delineated by integrating NDVI-based assessment with
      the impact assessment of anthropogenic impact sources. Second, the HM potential
      ecological risks index (PERI) is calculated and spatially interpolated. Finally,
      the EH with different PERI values are identified through logic calculation. Study
      results show that 45.2% of the study region has low HM risks, 53.2% with moderate
      HM risks, and only 1.6% with high HM risks. In addition, the percentage of EH
      with low HM risks is 6.5%; the percentage with moderate HM risks is 5.4%; and the
      percentage with high HM risks is 0.4%. The EH with low and moderate HM ecological
      risks are proposed to be the regions in priority for management. This approach is
      potentially useful to HM ecological risk assessment and HM contamination
      management around the world.

PMID- 22981744
TI  - Efficient removal of Cd2+ from aqueous solutions using by-product of biodiesel
      production.
AB  - In this study, chemically modified radish cake, a by-product of biodiesel
      production, was used to remove Cd(2+) from aqueous solutions. The chemical
      modification was carried out by treating the radish cake with citric acid (CRC),
      NaOH (NRC) or the combination of citric acid and NaOH (CNRC). The sorbents were
      characterized by elemental analysis, surface area analysis, infrared spectroscopy
      (FTIR), potentiometric titration (PT), scanning electron microscopy-energy
      dispersive spectroscopy (SEM-EDS), and thermogravimetric analysis (TGA). The
      effect of the chemical treatment and contact time on cadmium sorption was
      evaluated. The equilibrium data were analyzed using Freundlich and Langmuir
      models. The maximum sorption capacity obtained by the Langmuir isotherm was
      58.5mg/g and 64.10mg/g for the CRC, and CNRC sorbents, respectively. Complete
      desorption of Cd(2+) was achieved using 0.1 mol/L HNO(3). The results obtained
      demonstrate that chemically modified radish cake has potential as a sorbent for
      Cd(2+) removal from aqueous solutions.

PMID- 22981745
TI  - Metabolic ability and individual characteristics of an atrazine-degrading
      consortium DNC5.
AB  - A stable four-member bacterial consortium, DNC5 that was capable of metabolizing
      atrazine was isolated from corn-planted soil. The main objective of this paper is
      to characterize the individual metabolic characteristics and the mutualism of the
      cultivable members in the consortium DNC5. Substrates utilizing character of each
      community member indicate that the primary organism in this consortium is
      Arthrobacter sp. DNS10, which was the only strain capable of mineralizing
      atrazine to cyanuric acid. Two secondary strains (Bacillus subtilis DNS4 and
      Variovorax sp. DNS12) utilized cyanuric acid during the atrazine degradation
      process. Meanwhile, we found that a metabolite (isopropylamine) inhibited the
      atrazine degrading species Arthrobacter sp. DNS10. The last strain (Arthrobacter
      sp. DNS9) of this consortium played a role in reducing this inhibition by
      utilizing isopropylamine for its growth. Altogether this is a new combination of
      isolates in an atrazine degrading consortium. The growth and the degradation rate
      of consortium DNC5 were faster than that of the single strain DNS10. The high
      degradation ability of the consortium showed good potential for atrazine
      biodegradation. This study will contribute toward a better understanding about
      metabolic activities of atrazine degrading consortium, which are generally
      considered to be responsible for atrazine mineralization in the natural
      environment.

PMID- 22981746
TI  - Relevance of the measure of perceived exertion for the rehabilitation of obese
      patients.
AB  - The most common tool used for measuring effort perception is the rating scale of
      perceived exertion (RPE) developed by Borg. This scale is also used for various
      outcomes in the general population. The validity and reliability of this scale
      have already been reported in obese patients. However, the relevance of measuring
      perceived exertion in obese patients is still poorly known. This review of the
      literature presents the Borg RPE scale (i.e., validity, reliability and
      recommendations) and its main advantages during graded exercise tests (e.g.,
      comparison of physical capacity, predicting physiological variables, verifying
      exhaustion and exercise safety) and rehabilitation programs (e.g., individualized
      exercise intensity, evaluation of the impact of a rehabilitation program and even
      determining the perceptual preference) in obese patients. This review of the
      literature underlines the relevance and usefulness of the Borg RPE scale, which
      is still underused in obese patients. However, additional studies are still
      necessary before using this scale routinely in all obese patients (regardless of
      the severity of their obesity or associated complications).

PMID- 22981747
TI  - Development of a Lactobacillus specific T-RFLP method to determine lactobacilli
      diversity in complex samples.
AB  - Terminal restriction fragment length polymorphism (T-RFLP) analysis has been
      widely used for studying microbial communities. However, most T-RFLP assays use
      16S rDNA as the target and are unable to accurately characterize a microbial
      subpopulation. In this study, we developed a novel T-RFLP protocol based on
      Lactobacillus hsp60 to rapidly characterize and compare lactobacilli composition.
      The theoretical terminal restriction fragment (TRF) profiles were calculated from
      769 Lactobacillus hsp60 sequences from online databases. In silico digestion with
      restriction endonucleases AluI and TacI on hsp60 amplicons generated 83 distinct
      TRF patterns, of which, 70 were species specific. To validate the assay, five
      previously sequenced lactobacilli were cultured independently, mixed at known
      concentrations and subjected to analysis by T-RFLP. All five strains generated
      the predicted TRFs and a qualitative consistent relationship was revealed. We
      performed the T-RFLP protocol on fecal samples from mice fed 6 different diets
      (n=4). Principal component analysis and agglomerative hierarchical clustering
      revealed that the lactobacilli community was strongly connected to dietary
      supplementation. Our study demonstrates the potential for using Lactobacillus
      specific T-RFLP to characterize lactobacilli communities in complex samples.

PMID- 22981748
TI  - Early mobilization after ilio-inguinal lymph node dissection for melanoma does
      not increase the wound complication rate.
AB  - AIM: Ilio-inguinal lymph node dissection for stage III melanoma is accompanied by
      a substantial amount of wound complications. Our treatment protocols changed in
      time in terms of postoperative bed rest prescriptions, being in chronological
      order Group A: 10 days with a Bohler Braun splint, Group B: 10 days without
      splint, and Group C: 5 days without splint. The aim of this study was to evaluate
      the effect of bed rest prescriptions on wound complications. METHODS: For this
      study, we included all patients who underwent ilio-inguinal dissection for stage
      III melanoma in the period 1989-2011. Both univariate and multivariable analysis
      were performed to identify factors that were associated with occurrence of wound
      complications defined as wound infection, wound necrosis, and seroma. RESULTS: Of
      the 204 patients analyzed, 99 suffered one or more wound complications: 51 wound
      infection, 29 wound necrosis, and 39 seroma. A wound complication occurred in 26
      out of 64, 51 out of 89, and 22 out of 51 patients for Group A, B, and C,
      respectively. Univariate analysis showed age >55 (p = 0.001) and presence of
      comorbidity (p = 0.002) to be associated with higher incidence of wound
      complications. The 5 day bed rest protocol used in group C did not significantly
      increase the incidence of wound complications (ref = Group A: OR = 1.18; 95%CI =
      0.52-2.68, p = 0.698). CONCLUSION: Early mobilization did not significantly
      increase the overall wound complication rate after ilio-inguinal lymph node
      dissection for melanoma. Age >55 and comorbidity were risk factors in univariate
      analysis.

PMID- 22981749
TI  - A short-term follow-up of implant based breast reconstruction using a titanium
      coated polypropylene mesh (TiLoop((r)) Bra).
AB  - INTRODUCTION: A new approach for implant based breast reconstruction (IBBR) is
      the use of a titanium-coated polypropylene mesh (TCPM) as an alternative to
      acellular dermal matrix (ADM). This TCPM has a good biocompatibility and can be
      used similarly to ADM. The aim of this study is to discuss indications,
      limitations and complications of TCPM in IBBR. METHODS: A retrospective analysis
      of 42 patients undergoing immediate or delayed IBBR using a TCPM was performed.
      Primary endpoints were incidence of infection and expander/implant with mesh
      removal due to infected fluid collection or extrusion. RESULTS: In two patients,
      mild hematoma, seroma or infection occurred. Skin necrosis or capsular
      contraction was observed in one patient. Mesh explantation was needed in 3 cases.
      These events were higher among the first cases and in patients with postoperative
      skin infection (p = 0.003). CONCLUSION: In selected patients with adequate soft
      tissue cover TCPM seems to be a helpful tool for implant stabilization in terms
      of lateral stabilization and fixation of the musculus pectoralis major. In
      comparison to ADM, TCPM is cheaper and initial results are promising, but further
      follow-up data are necessary. In patients with poor soft tissue cover ADM should
      be used.

PMID- 22981750
TI  - A comparison of three methods for non-palpable breast cancer excision.

PMID- 22981751
TI  - Caspase 9 promoter polymorphisms confer increased susceptibility to breast
      cancer.
AB  - Caspases (CASPs), play a crucial role in the development and progression of
      cancer. We evaluated the association between two polymorphisms (rs4645978 and
      rs4645981) of the CASP9 gene and the risk of breast cancer (BC). Genotypes and
      allelic frequencies for the two polymorphisms were determined in 261 patients
      with breast cancer and 480 healthy controls. Polymerase chain reaction
      restriction fragment length polymorphisms were used, and statistical significance
      was determined by the chi(2) test. Carriers of the rs4645978G allele (AG and GG
      genotypes) were at higher risk for BC than individuals with other genotypes (odds
      ratio (OR) 1.59, 95% confidence interval (CI) 1.07-2.37, P = 0.022). The
      rs4645978GG genotype, in particular, was associated with the highest risk for BC
      development (OR 2.25, 95% CI 1.45-3.49, P = 0.0003). Similarly, individuals with
      at least one rs4645981T allele were at a significantly increased risk of
      developing BC compared with those harboring the CC genotype (OR 2.75, 95% CI 1.99
      3.78, P < 0.0001), and the risk of BC increased with increasing numbers of
      rs4645981T alleles (OR 2.66, 95% CI 1.91-3.69, P < 0.0001 for the CT genotype; OR
      3.95, 95% CI 1.58-9.88, P = 0.004 for the TT genotype). The CASP9 promoter
      polymorphisms rs4645978 and rs4645981 are associated with BC susceptibility and
      suggest that CASP9 transcriptional regulation is an important factor during BC
      development.

PMID- 22981752
TI  - A simple bone cyst of the distal humerus with a t(7;12)(q21;q24.3) in a patient
      with hypophosphatemic rickets.
AB  - Few studies describe karyotypic abnormalities in simple bone cysts. We report the
      results of cytogenetic analysis of a case of simple bone cyst of the distal
      humerus in a patient with hypophosphatemic rickets with a t(7;12)(q21;q24.3) as
      the sole abnormality. To our knowledge, this is the third report of a
      cytogenetically characterized tumor of this type.

PMID- 22981753
TI  - Polymer therapeutics-prospects for 21st century: the end of the beginning.
AB  - The term "polymer therapeutics" was coined to describe polymeric drugs, polymer
      conjugates of proteins, drugs and aptamers, together with those block copolymer
      micelles and multicomponent non-viral vectors which contain covalent linkages.
      These often complex, multicomponent constructs are actually "drugs" and
      "macromolecular prodrugs" in contrast to drug delivery systems that simply entrap
      (non-covalently) therapeutic agents. They have also been described as
      nanomedicines. First polymer-protein conjugates entered routine clinical use in
      1990 and a growing number of polymeric drugs/sequestrants and PEGylated
      proteins/aptamers have since come into the market. Valuable lessons have been
      learnt over >3 decades of clinical development, especially in relation to
      critical product attributes governing safety and efficacy, the validated methods
      needed for product characterisation. Not least there has been improved
      understanding of polymer therapeutic-specific biomarkers that will in future
      enable improved selection of patients for therapy. Advances in synthetic polymer
      chemistry (including control of 3D architecture), the move towards greater use of
      biodegradable polymers, polymers delivering combination therapy, increased
      understanding of polymer therapeutic critical product attributes to guide
      pharmaceutical development, and advances in understanding of endocytosis and
      intracellular trafficking pathways in health and disease are opening new
      opportunities for design and clinical use of polymer-based therapeutics in the
      decades to come.

PMID- 22981754
TI  - Inorganic nanosystems for therapeutic delivery: status and prospects.
AB  - Inorganic nanomaterials have an array of structural and physical properties that
      can be used in therapeutic delivery systems. The sizes, shapes, and surfaces of
      inorganic nanomaterials can be tailored to produce distinct interactions with
      biological systems both in vitro and in vivo. Nanoparticle cores can likewise be
      engineered to possess unique opticophysical properties, including upconversion,
      size-dependent absorbance/emission as well as magnetic properties such as
      superparamagnetism. These properties make inorganic nanomaterials as useful
      imaging agents for noninvasive diagnostics and remotely activated theragnostics.
      Taken together, these unique properties of inorganic nanomaterials make them
      promising delivery systems.

PMID- 22981756
TI  - Design of new quantum dot materials for deep tissue infrared imaging.
AB  - Near infrared fluorescence offers several advantages for tissue and in vivo
      imaging thanks to deeper photon penetration. In this article, we review a
      promising class of near infrared emitting probes based on semiconductor quantum
      dots (QDs), which have the potential to considerably improve in vivo fluorescence
      imaging thanks to their high brightness and stability. We discuss in particular
      the different criteria to optimize the design of near infrared QDs. We present
      the recent developments in the synthesis of novel QD materials and their
      different in vivo imaging applications, including lymph node localization,
      vasculature imaging, tumor localization, as well as cell tracking and QD-based
      multimodal probes.

PMID- 22981755
TI  - Emerging microtechnologies for the development of oral drug delivery devices.
AB  - The development of oral drug delivery platforms for administering therapeutics in
      a safe and effective manner across the gastrointestinal epithelium is of much
      importance. A variety of delivery systems such as enterically coated tablets,
      capsules, particles, and liposomes have been developed to improve oral
      bioavailability of drugs. However, orally administered drugs suffer from poor
      localization and therapeutic efficacy due to various physiological conditions
      such as low pH, and high shear intestinal fluid flow. Novel platforms combining
      controlled release, improved adhesion, tissue penetration, and selective
      intestinal targeting may overcome these issues and potentially diminish the
      toxicity and high frequency of administration associated with conventional oral
      delivery. Microfabrication along with appropriate surface chemistry, provide a
      means to fabricate these platforms en masse with flexibility in tailoring the
      shape, size, reservoir volume, and surface characteristics of microdevices.
      Moreover, the same technology can be used to include integrated circuit
      technology and sensors for designing sophisticated autonomous drug delivery
      devices that promise to significantly improve point of care diagnostic and
      therapeutic medical applications. This review sheds light on some of the
      fabrication techniques and addresses a few of the microfabricated devices that
      can be effectively used for controlled oral drug delivery applications.

PMID- 22981757
TI  - Wunderlich syndrome from lupus-associated vasculitis.
AB  - Spontaneous perinephric hemorrhage is a clinically rare life-threatening
      condition, also known as Wunderlich syndrome. Presentations can be variable, but
      patients typically display symptoms and signs including flank or abdominal pain,
      abdominal mass, and hypovolemia. It is important to diagnose the syndrome early
      because untreated cases carry a high mortality risk, and prompt intervention with
      an endovascular procedure or surgery is life saving. Causes range from anatomical
      anomalies, including vascular diseases (vasculitides and aneurysms) and renal
      tumors, to functional coagulation defect (bleeding tendency). The most common
      causes of Wunderlich syndrome are renal angiomyolipoma and renal cell carcinoma,
      constituting 60%~70% of cases. Vascular causes of Wunderlich syndrome are
      infrequent, and the culprit most frequently is vasculitis resulting from
      polyarteritis nodosa. Other vasculitides presenting as Wunderlich syndrome are
      infrequent. We describe a 39-year-old woman with end-stage renal disease from
      lupus nephritis and spontaneous renal hemorrhage, ascribed to lupus-related
      vasculitis after serologic testing, computed tomography, and angiographic
      studies.

PMID- 22981758
TI  - Relationship between mean platelet volume and coronary blood flow in patients
      with atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is associated with impaired coronary flow
      by means of Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC). Mean
      platelet volume (MPV) is elevated in patients with AF. In the present study we
      aimed to investigate the relationship between MPV and TFC in patients with AF in
      the absence of obstructive coronary artery disease (CAD). METHODS: This
      observational study enrolled 185 AF patients and 189 control subjects, all with
      angiographically documented normal coronary arteries. MPV was measured at
      baseline and mean TFC was assessed after diagnostic coronary angiography.
      RESULTS: The MPV was 9.95+/-1.32 in the AF group and 9.02+/-1.16 in the control
      group (p<0.001). In AF patients, MPV was significantly correlated with mean TFC
      (r=0.419, p<0.001), AF duration (r=0.407, p<0.001), AF classification (r=0.378,
      p<0.001), systemic hypertension (r=0.165, p=0.024), diabetes mellitus (r=0.233,
      p=0.001), left ventricular ejection fraction (r=-0.347, p<0.001), and baseline
      use of diuretics (r=0.177, p=0.016). In linear regression analysis, mean TFC,
      left ventricular ejection fraction and diabetes mellitus were found to be
      independently associated with MPV (p<0.001, p=0.028 and p=0.045 respectively).
      CONCLUSION: Mean platelet volume seems to be independently associated with
      coronary blood flow in patients with atrial fibrillation in the absence of
      obstructive coronary artery disease.

PMID- 22981759
TI  - Aortic stiffness in heritable aortopathies: relationship to aneurysm growth rate.
AB  - OBJECTIVE: This study compared aortic biomechanics in different heritable
      aortopathy syndromes and examined the clinical utility of aortic stiffness
      measurements. METHODS AND RESULTS: In 218 patients (55 Marfan, 47 bicuspid aortic
      valve (BAV), 47 isolated familial thoracic aneurysm (FTAD) and 69 matched
      controls) aortic biomechanics were measured by echocardiography with simultaneous
      blood pressure measurements. Patients were stratified by age as <=40 years or >40
      years. Aortic stiffness increased with age and aortic biomechanics were abnormal
      in all aortopathies, particularly in BAV and FTAD. Increased stiffness and pulse
      wave velocity were seen in BAV and FTAD in both age cohorts (p<0.001) and both
      were stiffer than Marfan patients (p<0.01). Marfan patients aged <=40 years had
      stiffer aortas than controls, but those >40 years were similar to controls.
      Multivariate regression identified age as the dominant correlate with increased
      stiffness, and also aortic diameter and mean blood pressure (R(2)=0.64; p<0.001).
      Aortopathy patients with stiffness index>16 had lower rate of increase in aortic
      diameter (0.25+/-0.30 mm/year) than those with normal stiffness (0.68+/-0.39
      mm/year, p<0.001). Whilst positive predictive value of increased stiffness for
      detection of aortopathy was high (93% in age<=40 years, 87%, in age>40 years),
      negative predictive accuracy was low (55% and 34% respectively). CONCLUSION:
      Abnormal biomechanics are common to all aortopathies, with greater abnormality in
      BAV and FTAD than in Marfan. Increased aortic stiffness is associated with slower
      rate of aneurysm progression.

PMID- 22981760
TI  - Sampling methods for the study of pneumococcal carriage: a systematic review.
AB  - Streptococcus pneumoniae is an important pathogen worldwide. Accurate sampling of
      S. pneumoniae carriage is central to surveillance studies before and following
      conjugate vaccination programmes to combat pneumococcal disease. Any bias
      introduced during sampling will affect downstream recovery and typing. Many
      variables exist for the method of collection and initial processing, which can
      make inter-laboratory or international comparisons of data complex. In February
      2003, a World Health Organisation working group published a standard method for
      the detection of pneumococcal carriage for vaccine trials to reduce or eliminate
      variability. We sought to describe the variables associated with the sampling of
      S. pneumoniae from collection to storage in the context of the methods
      recommended by the WHO and those used in pneumococcal carriage studies since its
      publication. A search of published literature in the online PubMed database was
      performed on the 1st June 2012, to identify published studies that collected
      pneumococcal carriage isolates, conducted after the publication of the WHO
      standard method. After undertaking a systematic analysis of the literature, we
      show that a number of differences in pneumococcal sampling protocol continue to
      exist between studies since the WHO publication. The majority of studies sample
      from the nasopharynx, but the choice of swab and swab transport media is more
      variable between studies. At present there is insufficient experimental data that
      supports the optimal sensitivity of any standard method. This may have
      contributed to incomplete adoption of the primary stages of the WHO detection
      protocol, alongside pragmatic or logistical issues associated with study design.
      Consequently studies may not provide a true estimate of pneumococcal carriage.
      Optimal sampling of carriage could lead to improvements in downstream analysis
      and the evaluation of pneumococcal vaccine impact and extrapolation to
      pneumococcal disease control therefore further in depth comparisons would be of
      value.

PMID- 22981761
TI  - Rabies vaccine standards: comparison of the 5th and 6th WHO international
      reference standards to the USDA veterinary reference standard.
AB  - Ensuring rabies vaccines are potent and effective is paramount in preventing
      transmission of this deadly disease and safeguarding public health. Efficacy of
      human and veterinary vaccines is ensured by evaluating relative potency estimates
      of the vaccine compared to a rabies reference standard using the National
      Institutes of Health (NIH) test. Reference vaccines are based on the
      International Standard for Rabies Vaccine provided by the World Health
      Organization (WHO). A comparison study was conducted to determine the relative
      potency of the 5th WHO, 6th WHO, and United States Department of Agriculture's
      (USDA) 08-14 reference standards using the NIH test. Results from the study
      demonstrate that the 6th WHO reference standard is approximately twice as potent
      as the 5th WHO reference when reconstituted to contain 1 IU per ml. Based on
      these results, the Center for Veterinary Biologics (CVB) doubled the
      reconstitution volume of USDA veterinary reference 08-14 from 13 ml to 26 ml, for
      an initial use dilution of 0.7 IU per ml for use by veterinary biologics
      manufacturers in the NIH test. This study emphasizes the importance of reference
      standard calibration for use in the National Institutes of Health test.

PMID- 22981762
TI  - The importance of pertussis in older adults: a growing case for reviewing
      vaccination strategy in the elderly.
AB  - Pertussis or whooping cough is increasingly being shown to be a respiratory
      infection affecting the elderly and a significant percentage of older people
      infected with Bordetella pertussis experience considerable morbidity and even
      mortality. However, current knowledge of burden of disease is limited largely to
      passive surveillance data with little well-designed active surveillance to better
      ascertain the true burden of pertussis in the elderly, to inform vaccination
      strategies. The current review aims to identify gaps in knowledge to inform
      policy considerations relating to pertussis vaccination among the elderly.

PMID- 22981763
TI  - Differences in avidity of IgG antibodies to pertussis toxin after acellular
      pertussis booster vaccination and natural infection.
AB  - BACKGROUND: Pertussis toxin (PT) is a specific virulence factor of Bordetella
      pertussis and it is included in all acellular pertussis vaccines (aP). Although
      immunity after infection seems to persist longer than that after vaccination, the
      exact mechanism(s) is not known. Primary aim of this study was to develop an
      ELISA method for measuring avidity index (AI) of IgG-anti-PT antibodies and to
      compare antibody responses after booster vaccination and infection. Secondary aim
      was to evaluate if the AI-ELISA has potential in the serodiagnosis of pertussis.
      MATERIAL: Serum samples from a total of 409 subjects were included in the study.
      Paired sera were taken from 97 adolescents who received booster vaccine ten years
      ago (dTpa-004) and from 80 young adults who received a second booster dose ten
      years after the previous booster vaccine (dTpa-040). Thirty-two paired sera from
      culture-confirmed pertussis patients, 161 single sera from serologically
      diagnosed patients and 39 single sera from healthy controls were included. AI of
      IgG-anti-PT antibodies were determined with newly developed ELISA using
      diethylamine (DEA) as a bond breaking agent. The IgG-anti-PT antibodies were
      measured by standardized ELISA. RESULTS: A significant increase was found in
      antibody concentrations and AI between PRE and one month POST vaccination ten
      years ago [GMC for antibody: 7.9 IU/ml vs. 98.3 IU/ml (p=0.0001); for AI: 40.4%
      vs. 56.1% (p=0.0001)]. Similar result was observed after the second booster dose
      [GMC for antibody: 9.2 IU/ml vs. 92.4 IU/ml (p=0.0001); for AI: 36.1% vs. 59.5%
      (p=0.0001)] and between the first and second sera of culture-confirmed patients
      [GMC for antibody: 6.9 IU/ml vs. 285.1 IU/ml (p=0.0001); for AI: 40.5% vs. 68.4%
      (p=0.0001)]. Healthy controls showed lower levels of both antibodies and AI.
      CONCLUSIONS: Our results suggest that there may be difference in quality and
      quantity of antibodies to PT after vaccination and after infection. Furthermore,
      AI could be a help for vaccine studies.

PMID- 22981764
TI  - Multi-antigenic vaccine against the cattle tick Rhipicephalus (Boophilus)
      microplus: a field evaluation.
AB  - The tick Rhipicephalus (Boophilus) microplus is a blood-sucking ectoparasite of
      cattle that severely impairs livestock production. Studies on tick immunological
      control address mostly single-antigen vaccines. However, from the commercial
      standpoint, so far no single-antigen vaccine has afforded appropriate protection
      against all R. microplus populations. In this context, multi-antigen cocktails
      have emerged as a way to enhance vaccine efficacy. In this work, a multi
      antigenic vaccine against R. microplus was analyzed under field conditions in
      naturally infested cattle. The vaccine was composed by three tick recombinant
      proteins from two tick species that in previous single-vaccination reports
      provided partial protection of confined cattle against R. microplus infestations:
      vitellin-degrading cysteine endopeptidase (VTDCE) and boophilus yolk pro
      cathepsin (BYC) from R. microplus, and glutathione S-transferase from
      Haemaphysalis longicornis (GST-Hl). Increased antibody levels against three
      proteins were recorded after immunizations, with a distinct humoral immune
      response dynamics for each protein. Compared to the control group, a
      statistically significant lower number of semi-engorged female ticks were
      observed in vaccinated cattle after two inoculations. This reduction persisted
      for 3 months, ranging from 35.3 to 61.6%. Furthermore, cattle body weight gain
      was significantly higher in vaccinated animals when compared to control cattle.
      Compared to the single-antigen vaccines composed by VTDCE, BYC or GST-Hl, this
      three-antigen vaccine afforded higher protection levels against R. microplus
      infestations.

PMID- 22981765
TI  - Volume sweeping and bodyline matching for automated prealignment in volumetric
      medical image registration.
AB  - For an automated image registration to converge to a good registration, it is
      crucial that the initial registration is within the capture range of the true
      registration, as local optimization methods are frequently employed. The ways to
      set an initial registration in current practice are not ideal and it is highly
      desirable to automate this initial registration (prealignment). Two automatic
      prealignment methods are reported here. In the volume sweeping approach, one
      volume is swept through the other, the overlapping volumes are coarsely aligned
      in the x and y directions, and a similarity measure is calculated at each
      sweeping position. Once sweeping is done, the position that gives the best
      similarity measure is chosen as the prealignment. In the second bodyline matching
      approach, patient bodyline profiles (the furthest anterior or posterior body
      boundary points) are extracted from two volumes and objectively matched. A
      prealignment is then derived from the matched bodylines. Both methods are tested
      on 19 PET/CT alignments of five patients with known ground truths acquired on
      hybrid PET/CT scanners. The absolute differences in the three translational
      parameters between the volume sweeping prealignment and the ground truth are 6.1
      +/- 3.9, 2.2 +/- 2.7, and 4.2 +/- 6.1mm, and between the bodyline matching and
      the ground truth are 5.2 +/- 3.0, 3.3 +/- 3.0, and 3.3 +/- 4.1mm, which are
      within the capture range of automatic registration algorithms. The volume
      sweeping and bodyline matching can thus be used as a preprocessing step for
      automatic registration, making it possible to run an automatic registration
      algorithm without user intervention.

PMID- 22981766
TI  - Self-expanding aortic valve stent-material optimization.
AB  - Vascular support structures are important devices for treating valve stenosis.
      Large population of patients is treated for valvular disease and the principal
      mode of treatment is the use of percutaneous valvuloplasty. Stent devices are
      proving to be an improved technology in minimal invasive cardiac surgery. This
      technology now accounts for 20% of treatments in Europe. This new technology
      provides highly effective results at minimal cost and short duration of
      hospitalization. During the development process, a number of specific designs and
      materials have come and gone, and a few have remained. Many design changes were
      successful, and many were not. This paper discusses the physical behavior of a
      hooked percutaneous aortic valve stent design using a finite element analysis.
      Specifically, the effects of crimping was simulated and analyzed for two types of
      realistic but different Nitinol materials (NITI-1 and NITI-2). The results show
      that both NITI-1 and NITI-2 had good crimping performance. The analysis performed
      in this paper may aid in understanding the stent's displacement ranges when
      subjected to physiological pressures exerted by the heart and cardiac blood flow
      during abnormal cardiovascular conditions. It may also help to evaluate the
      suitability of a Nitinol for fabrication purposes.

PMID- 22981767
TI  - The influence of the number of cells scored on the sensitivity in the comet
      assay.
AB  - The impact on the sensitivity of the in vitro comet assay by increasing the
      number of cells scored has only been addressed in a few studies. The present
      study investigated whether the sensitivity of the assay could be improved by
      scoring more than 100 cells. Two cell lines and three different chemicals were
      used: Caco-2 cells were exposed to ethylmethane sulfonate and hydrogen peroxide
      in three concentrations, and HepG2 cells were exposed to ethylmethane sulfonate,
      hydrogen peroxide and benzo[a]pyrene in up to four concentrations, in four to
      five independent experiments. The scoring was carried out by means of a fully
      automated scoring system and the results were analyzed by evaluating the % tail
      DNA of 100-700 randomly selected cells for each slide consisting of two gels. By
      increasing the number of cells scored, the coefficients of variance decreased,
      leading to an improved sensitivity of the assay. A two-way ANOVA analysis of
      variance showed that the contribution from the two variables "the number of cells
      scored" and "concentration" on the total variation in the coefficients of
      variance dataset was statistically significant (p<0.05). The increase in
      sensitivity was demonstrated by the possibility to detect an increase in % tail
      DNA with statistical significance at lower concentrations. The results indicated
      that for low levels of DNA damage, below 9% tail DNA, scoring of 600 cells
      increased the sensitivity compared with scoring of 100 cells. For relatively low
      levels of DNA damage, about 9-16% tail DNA, scoring of 300 cells increased the
      sensitivity. Thus, the recommendation for the optimum number of cells scored
      would be 600 and 300 for low and relatively low levels of DNA damage,
      respectively. The findings from this study could be particularly important for
      bio-monitoring studies where small differences in DNA-damage levels could be
      relevant.

PMID- 22981768
TI  - Intake of a resveratrol-containing dietary supplement has no impact on DNA
      stability in healthy subjects.
AB  - It has been postulated that the beneficial health effects of dietary supplements
      and of red wines which contain resveratrol (RES) are due to the anti-oxidative
      properties of this phenolic compound, but evidence for protection against
      reactive oxygen species is mainly based on results of in vitro experiments and
      high-dose animal experiments. Aim of this study was to find out if intake of a
      RES-containing supplement protects healthy humans against oxidative DNA-damage
      and alters their redox status. Therefore, an intervention trial was conducted in
      which the participants (n=12) consumed a RES-containing supplement over a period
      of five days. At the start, after one day and after five days of consumption, and
      after a washout period DNA stability was measured in single cell gel
      electrophoresis (SCGE) assays with peripheral blood lymphocytes. These tests were
      conducted (a) under standard conditions, which reflect single- and double-strand
      DNA breaks, (b) after treatment of the cells with hydrogen peroxide, which
      enables detection of alterations of the ROS sensitivity, and (c) by use of
      formamidopyrimidine DNA-glycosylase (FPG), which provides information on
      formation of oxidatively damaged bases (pyrimidines). Furthermore, the
      biochemical parameters TAC (total antioxidant capacity) and oxLDL (oxidized low
      density lipoprotein), which reflect the redox status, and C-reactive protein
      (CRP), a marker of inflammation, were monitored. The intake of the supplement had
      no significant impact on the DNA stability parameters and on the different
      biomarkers of the redox status. Our results indicate that intake of 6mg RES per
      day via the supplement does not cause DNA-protective or antioxidant effects. This
      amount is equivalent to or lower than that reached after intake of many (ca. 50%)
      of the RES-containing preparations which are currently on the market in Middle
      Europe, and is contained in 0.3-2L red wine.

PMID- 22981769
TI  - Assessing LINE-1 retrotransposition activity in neuroblastoma cells exposed to
      extremely low-frequency pulsed magnetic fields.
AB  - Mobile genetic elements represent an important source of mutation and genomic
      instability, and their activity can be influenced by several chemical and
      physical agents. In this research we address the question whether exposure to
      extremely low-frequency pulsed magnetic fields (EMF-PMF) could affect the
      mobility of the human LINE-1(RP) retrotransposon. To this purpose, an in vitro
      retrotransposition assay was used on human neuroblastoma BE(2) cells exposed for
      48h to 1mT, 50Hz PMF, or sham-exposed. Moreover, since it is well known that
      retrotransposition causes DNA double-strand breaks (DSB), an estimation of gamma
      H2AX foci, which is a marker of DNA DSB, was carried out on PMF- and sham-exposed
      samples. The results show that PMF-exposed cells had a lower number of both
      retrotransposition events and DNA DSB compared with sham-exposed samples. These
      results suggest that exposure to PMF can interfere with retrotransposition
      activity by inducing a decrease of retrotransposition events.

PMID- 22981770
TI  - SID-5 is an endosome-associated protein required for efficient systemic RNAi in
      C. elegans.
AB  - In the nematode C. elegans, RNAi silencing signals are efficiently taken up from
      the environment and transported between cells and tissues. Previous studies
      implicating endosomal proteins in systemic RNAi lack conclusive evidence. Here,
      we report the identification and characterization of SID-5, a C. elegans endosome
      associated protein that is required for efficient systemic RNAi in response to
      both ingested and expressed double-stranded RNA (dsRNA). SID-5 is detected in
      cytoplasmic foci that partially colocalize with GFP fusions of late endosomal
      proteins RAB-7 and LMP-1. Furthermore, knockdown of various endosomal proteins
      similarly relocalizes both SID-5 and LMP-1::GFP. Consistent with a non-cell
      autonomous function, intestine-specific SID-5 expression restored body wall
      muscle (bwm) target gene silencing in response to ingested dsRNA. Finally, we
      show that sid-5 is required for the previously described sid-1-independent
      transport of ingested RNAi triggers across the intestine. Together, these data
      demonstrate that an endosome-associated protein, SID-5, promotes the transport of
      RNAi silencing signals between cells. Furthermore, SID-5 acts differently than
      the previously described SID-1, SID-2, and SID-3 proteins, thus expanding the
      systemic RNAi pathway.

PMID- 22981771
TI  - Specialization of mutualistic interaction networks decreases toward tropical
      latitudes.
AB  - Species-rich tropical communities are expected to be more specialized than their
      temperate counterparts. Several studies have reported increasing biotic
      specialization toward the tropics, whereas others have not found latitudinal
      trends once accounting for sampling bias or differences in plant diversity. Thus,
      the direction of the latitudinal specialization gradient remains contentious.
      With an unprecedented global data set, we investigated how biotic specialization
      between plants and animal pollinators or seed dispersers is associated with
      latitude, past and contemporary climate, and plant diversity. We show that in
      contrast to expectation, biotic specialization of mutualistic networks is
      significantly lower at tropical than at temperate latitudes. Specialization was
      more closely related to contemporary climate than to past climate stability,
      suggesting that current conditions have a stronger effect on biotic
      specialization than historical community stability. Biotic specialization
      decreased with increasing local and regional plant diversity. This suggests that
      high specialization of mutualistic interactions is a response of pollinators and
      seed dispersers to low plant diversity. This could explain why the latitudinal
      specialization gradient is reversed relative to the latitudinal diversity
      gradient. Low mutualistic network specialization in the tropics suggests higher
      tolerance against extinctions in tropical than in temperate communities.

PMID- 22981772
TI  - Faster perceptual learning through excitotoxic neurodegeneration.
AB  - Glutamatergic neural transmission is involved in both neural plasticity and
      neurodegeneration. This combination of roles could result in ambivalent effects
      in which excitotoxic neurodegeneration augments neural plasticity in parallel.
      Neural plasticity can be induced by exposure-based learning (EBL) that resembles
      timing properties of long-term potentiation (LTP) protocols (i.e., LTP-like
      learning). Even though it has not been demonstrated so far in animal models that
      perceptual effects of such stimulation protocols are mediated by typical LTP
      mechanisms, it has been shown that exposure-based learning exerts strong effects
      on cognitive brain functioning and is modulated by glutamatergic neural
      transmission. We reveal that exposure-based perceptual learning is more efficient
      in a human model of excitotoxic neurodegeneration than in healthy participants.
      Premanifest Huntington's disease gene mutation carriers showed faster increases
      in perceptual sensitivities than controls. This in turn changed attentional
      processing in extrastriate visual areas objectified using electroencephalogram
      data. The emergence of faster learning correlated positively with genetic disease
      load. Our results confirm an ambivalent action of increased glutamatergic
      transmission, implying that the process of excitotoxic neurodegeneration is
      associated with enhanced perceptual learning, which can be used to improve
      attentional and behavioral control via the alteration of perceptual
      sensitivities.

PMID- 22981773
TI  - A genome-wide functional screen shows MAGI-1 is an L1CAM-dependent stabilizer of
      apical junctions in C. elegans.
AB  - BACKGROUND: In multicellular organisms, cell-cell junctions are involved in many
      aspects of tissue morphogenesis. alpha-catenin links the cadherin-catenin complex
      (CCC) to the actin cytoskeleton, stabilizing cadherin-dependent adhesions.
      RESULTS: To identify modulators of cadherin-based cell adhesion, we conducted a
      genome-wide RNAi screen in C. elegans and uncovered MAGI-1, a highly conserved
      protein scaffold. Loss of magi-1 function in wild-type embryos results in
      disorganized epithelial migration and occasional morphogenetic failure. MAGI-1
      physically interacts with the putative actin regulator AFD-1/afadin; knocking
      down magi-1 or afd-1 function in a hypomorphic alpha-catenin background leads to
      complete morphogenetic failure and actin disorganization in the embryonic
      epidermis. MAGI-1 and AFD-1 localize to a unique domain in the apical junction
      and normal accumulation of MAGI-1 at junctions requires SAX-7/L1CAM, which can
      bind MAGI-1 via its C terminus. Depletion of MAGI-1 leads to loss of spatial
      segregation and expansion of apical junctional domains and greater mobility of
      junctional proteins. CONCLUSIONS: Our screen is the first genome-wide approach to
      identify proteins that function synergistically with the CCC during epidermal
      morphogenesis in a living embryo. We demonstrate novel physical interactions
      between MAGI-1, AFD-1/afadin, and SAX-7/L1CAM, which are part of a functional
      interactome that includes components of the core CCC. Our results further suggest
      that MAGI-1 helps to partition and maintain a stable, spatially ordered apical
      junction during morphogenesis.

PMID- 22981774
TI  - Circadian rhythm of temperature preference and its neural control in Drosophila.
AB  - A daily body temperature rhythm (BTR) is critical for the maintenance of
      homeostasis in mammals. Whereas mammals use internal energy to regulate body
      temperature, ectotherms typically regulate body temperature behaviorally [1].
      Some ectotherms maintain homeostasis via a daily temperature preference rhythm
      (TPR) [2], but the underlying mechanisms are largely unknown. Here, we show that
      Drosophila exhibit a daily circadian clock-dependent TPR that resembles mammalian
      BTR. Pacemaker neurons critical for locomotor activity are not necessary for TPR;
      instead, the dorsal neuron 2 s (DN2s), whose function was previously unknown, is
      sufficient. This indicates that TPR, like BTR, is controlled independently from
      locomotor activity. Therefore, the mechanisms controlling temperature
      fluctuations in fly TPR and mammalian BTR may share parallel features. Taken
      together, our results reveal the existence of a novel DN2-based circadian neural
      circuit that specifically regulates TPR; thus, understanding the mechanisms of
      TPR will shed new light on the function and neural control of circadian rhythms.

PMID- 22981776
TI  - Ethics for end-of-life treatments: metastatic colorectal cancer is one example.
AB  - The number of biological agents (BAs) registered with an indication related to
      cancer treatment is flourishing and the cost of these treatments is rising
      dramatically, making the situation potentially unsustainable for healthcare
      systems. Here we focus on the examples of bevacizumab (BV) and cetuximab (CX),
      two BAs approved for metastatic colorectal cancer (mCRC). The first clinical
      trials show an increase in median overall survival of a few months, though these
      results could not always be repeated in subsequent studies. We reviewed full
      economic evaluations (FEEs) on BV or CX and despite frequently arguable estimates
      based on indirect efficacy, only one estimated the addition of CX was cost
      effective in a virtual subgroup of patients, albeit with flawed methods. Most
      Western European countries reimburse BV and CX for mCRC, though clinical evidence
      seems weak and economic evidence even absent. The underlying question is whether
      national health authorities are prepared to spend an increasing share of
      healthcare budgets on very expensive end-of-life treatments, their impact on life
      expectancy (a few additional months at best) and QoL (enhanced mainly by
      patients' hopes) being doubtful and their cost-effectiveness hardly ever proved.
      Further research is needed to explore how ethics could be included and thus
      assessed under these circumstances.

PMID- 22981775
TI  - The centrosome regulates the Rab11- dependent recycling endosome pathway at
      appendages of the mother centriole.
AB  - The recycling endosome localizes to a pericentrosomal region via microtubule
      dependent transport. We previously showed that Sec15, an effector of the
      recycling endosome component, Rab11-GTPase, interacts with the mother centriole
      appendage protein, centriolin, suggesting an interaction between endosomes and
      centrosomes. Here we show that the recycling endosome associates with the
      appendages of the mother (older) centriole. We show that two mother centriole
      appendage proteins, centriolin and cenexin/ODF2, regulate association of the
      endosome components Rab11, the Rab11 GTP-activating protein Evi5, and the exocyst
      at the mother centriole. Development of an in vitro method for reconstituting
      endosome protein complexes onto isolated membrane-free centrosomes demonstrates
      that purified GTP-Rab11 but not GDP-Rab11 binds to mother centriole appendages in
      the absence of membranes. Moreover, centriolin depletion displaces the
      centrosomal Rab11 GAP, Evi5, and increases mother-centriole-associated Rab11;
      depletion of Evi5 also increases centrosomal Rab11. This indicates that
      centriolin localizes Evi5 to centriolar appendages to turn off centrosomal Rab11
      activity. Finally, centriolin depletion disrupts recycling endosome organization
      and function, suggesting a role for mother centriole proteins in the regulation
      of Rab11 localization and activity at the mother centriole.

PMID- 22981777
TI  - Cervical spine mobility analysis on radiographs: a fully automatic approach.
AB  - Conventional X-ray radiography remains nowadays the most common method to analyze
      spinal mobility in two dimensions. Therefore, the objective of this paper is to
      develop a framework dedicated to the fully automatic cervical spine mobility
      analysis on X-ray images. To this aim, we propose an approach based on three main
      steps: fully automatic vertebra detection, vertebra segmentation and angular
      measurement. The accuracy of the method was assessed for a total of 245
      vertebrae. For the vertebra detection, we proposed an adapted version of two
      descriptors, namely Scale-invariant Feature Transform (SIFT) and Speeded-up
      Robust Features (SURF), coupled with a multi-class Support Vector Machine (SVM)
      classifier. Vertebrae are successfully detected in 89.8% of cases and it is
      demonstrated that SURF slightly outperforms SIFT. The Active Shape Model approach
      was considered as a segmentation procedure. We observed that a statistical shape
      model specific to the vertebral level improves the results. Angular errors of
      cervical spine mobility are presented. We showed that these errors remain within
      the inter-operator variability of the reference method.

PMID- 22981778
TI  - A protein delivery system using 30Kc19 cell-penetrating protein originating from
      silkworm.
AB  - Cell-penetrating protein and its protein transduction domain have been used to
      deliver drugs and proteins into the cells via receptor-independent endocytosis. A
      number of cell-penetrating proteins including TAT derived from HIV-1 virus, VP22
      from herpes simplex virus and Antennapedia from drosophila have been discovered.
      Here, we report a cell-penetrating protein, 30Kc19, originating from the
      hemolymph of silkworm, Bombyx mori. The 30Kc19 is the first cell-penetrating
      protein that has been found in insect hemolymph. When the 30Kc19 protein produced
      from recombinant Escherichia coli was supplemented into the medium for mammalian
      cell culture, 30Kc19 efficiently penetrated into various types of cells and
      localized at subcellular compartments including mitochondria and cytoplasm.
      30Kc19 also delivered cargo proteins such as green fluorescence protein into the
      cells even though cargo proteins are not able to penetrate into cells by
      themselves. In addition to the in vitro system, 30Kc19 exhibited the protein
      transduction property in vivo. When 30Kc19 was intraperitoneally injected into
      mice, 30Kc19 delivered cargo proteins into various organ tissues of model animals
      without producing toxicity. Therefore, 30Kc19 has a great potential as a cell
      penetrating protein that can be used as a medicinal tool to deliver cargo
      molecules including proteins into the target organ tissues in the body.

PMID- 22981779
TI  - Angiogenic and osteogenic potential of platelet-rich plasma and adipose-derived
      stem cell laden alginate microspheres.
AB  - Improving vascularization of tissue-engineered bone can advance cell performance
      in vivo and further promote bone regeneration. How to achieve a functional
      vascular network within the construct is one of the biggest challenges so far. We
      hypothesized that a mixture of platelet-rich plasma (PRP) and adipose-derived
      stem cells (ADSCs) could endue the alginate microspheres with osteogenic and
      angiogenic potential. In vitro and in vivo studies were performed to investigate
      the potential of the PRP-ADSC-laden microspheres. Two intriguing observations
      were made in this study. First, we demonstrated that PRP sustained cell viability
      and meanwhile promoted cell migration from the interior of alginate microspheres
      to the surface. This phenomenon indicated that encapsulated cells have the
      potential to directly and actively participate into the regeneration process.
      Second, in vivo, a blood vessel network was found within the 10% PRP and 15% PRP
      ADSC implants, which was associated with a significant increase in
      mineralization. It suggested that the PRP-ADSC-laden microspheres did enhance the
      vascularization and mineralization. In summary, this strategy not only provides a
      micro-invasive therapy for bone regeneration, but also could be incorporated with
      other matrices for extended application.

PMID- 22981780
TI  - Cardiovascular epigenetics: from DNA methylation to microRNAs.
AB  - Epigenetic phenomena are defined as heritable mechanisms that establish and
      maintain mitotically stable patterns of gene expression without modifying the
      base sequence of DNA. The major epigenetic features of mammalian cells include
      DNA methylation, post-translational histone modifications and RNA-based
      mechanisms including those controlled by small non-coding RNAs (miRNAs). The
      impact of epigenetic mechanisms in cardiovascular pathophysiology is now emerging
      as a major player in the interface between genotype to phenotype variability.
      This topic of research has strict implications on disease development and
      progression, and opens up possible novel preventive strategies in cardiovascular
      disease. An important aspect of epigenetic mechanisms is that they are
      potentially reversible and may be influenced by nutritional-environmental factors
      and through gene-environment interactions, all of which have an important role in
      complex, multifactorial diseases such as those affecting the cardiovascular
      system. Gene expression regulation through the interplay of DNA methylation and
      histone modifications is well-established, although the knowledge about the
      function of epigenetic signatures in cardiovascular disease is still largely
      unexplored. The study of epigenetic markers is, therefore, a very promising
      frontier of science which may aid in a deeper understanding of molecular
      mechanisms underlying the modulation of gene expression in the biomolecule
      pathways linked to cardiovascular diseases. This review focuses on up-to-date
      knowledge pertaining to the role of epigenetics, from DNA methylation to miRNAs,
      in major cardiovascular diseases such as ischemic heart disease, hypertension,
      heart failure and stroke.

PMID- 22981781
TI  - Effects of chemical composition of fly ash on efficiency of metal separation in
      ash-melting of municipal solid waste.
AB  - In the process of metal separation by ash-melting, Fe and Cu in the incineration
      residue remain in the melting furnace as molten metal, whereas Pb and Zn in the
      residue are volatilized. This study investigated the effects of the chemical
      composition of incineration fly ash on the metal-separation efficiency of the ash
      melting process. Incineration fly ash with different chemical compositions was
      melted with bottom ash in a lab-scale reactor, and the efficiency with which Pb
      and Zn were volatilized preventing the volatilization of Fe and Cu was evaluated.
      In addition, the behavior of these metals was simulated by thermodynamic
      equilibrium calculations. Depending on the exhaust gas treatment system used in
      the incinerator, the relationships among Na, K, and Cl concentrations in the
      incineration fly ash differed, which affected the efficiency of the metal
      separation. The amounts of Fe and Cu volatilized decreased by the decrease in the
      molar ratio of Cl to Na and K in the ash, promoting metal separation. The
      thermodynamic simulation predicted that the chlorination volatilization of Fe and
      Cu was prevented by the decrease in the molar ratio, as mentioned before. By
      melting incineration fly ash with the low molar ratio in a non-oxidative
      atmosphere, most of the Pb and Zn in the ash were volatilized leaving behind Fe
      and Cu.

PMID- 22981782
TI  - Phosphaturic mesenchymal tumor: a report of 6 patients treated at a single
      institution and comparison with reported series.
AB  - Osteogenic osteomalacia (OO)-associated phosphaturic mesenchymal tumors (PMTs)
      might represent a single histopathologic paraneoplastic entity. These tumors are
      largely misunderstood, ignored, or unknown by pathologists and clinicians. To
      elucidate the characteristics of OO-associated PMTs, we retrospectively analyzed
      the clinicopathologic features of PMTs from 6 patients, with either known OO or
      features suggestive of PMT-mixed connective tissue variant, who were studied and
      managed at a single center during the period from 1993 to 2011. Histologically,
      the tumor showed proliferation of spindle cells with focal areas of matrix
      production that showed distinct calcification, ossification, and osteoid-like
      matrix. Two patients had no evidence of disease and normal biochemical values;
      the other 2 patients each had multiple surgeries for multiple recurrences. In
      conclusion, PMT is histologically a benign lesion, with the malignant and
      metastatic variant being extremely rare. Infiltration of surrounding tissue is a
      frequent feature that is best managed with complete surgical removal of all
      involved tissue, which dramatically resolves the tumor-associated osteomalacia. 

PMID- 22981783
TI  - Histological examination of ulcer margin for diagnosing Helicobacter pylori
      infection in patients with gastric ulcers.
AB  - Biopsy of ulcer margin is routinely performed to exclude malignancy in patients
      with gastric ulcers, but its utility in diagnosing Helicobacter pylori infection
      has not yet been fully studied. A cohort of 50 patients with gastric ulcer was
      prospectively examined. Three tests including histology, rapid urease test, and
      urea breath test were performed in all patients for diagnosing H pylori
      infection. Six biopsied specimens from the margin of the gastric ulcer and 1 each
      specimen from antrum and body of non-ulcer part were obtained for histology using
      hematoxylin-eosin (H&E) stain. The criterion used for defining H pylori infection
      was a positive result in at least 2 of the 3 tests. H pylori infection was
      diagnosed in 27 (54%) of the patients. The diagnostic sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of the
      histological examination of the ulcer margin were 92.6%, 95.7%, 96.2%, 91.7%, and
      94%, respectively. The addition of 1 specimen from the antrum or body or a
      combination of the 2 specimens did not increase the diagnostic yields of those
      for histological examination of ulcer margin alone. The diagnostic sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      for the rapid urease test were 96.3%, 100%, 100%, 95.8%, and 98%, respectively,
      and the corresponding values for the urea breath test were 88.9%, 87%, 88.9%,
      87%, and 88%. We performed Giemsa stain for the 3 patients with false-negative
      and false-positive results of histological examination of ulcer margin using H&E
      stain, and all were positive for H pylori infection. In conclusion, histological
      examination of the ulcer margin using hematoxylin-eosin stain was quite accurate
      and useful for diagnosing H pylori infection in patients with gastric ulcers. A
      special stain is required when the diagnosis of H pylori infection is
      questionable on routine H&E staining.

PMID- 22981784
TI  - Intractable hiccups: a rare presentation of phrenic nerve schwannoma.
AB  - INTRODUCTION: Schwannoma rarely involves the phrenic nerve. We report a unique
      case of schwannoma as a cause of chronic hiccups due to the involvement of
      phrenic nerve. CASE PRESENTATION: A 72-year-old male presented with 20-year
      history of hiccups. He underwent multiple esophagogastroduodenoscopy procedures,
      all of which were negative. A computed tomography (CT-scan) of soft tissue of the
      neck was remarkable for left retrosternal mass with central calcification,
      located adjacent to the thyroid gland. He underwent surgery and this mass was
      found to be originating from the left phrenic nerve. Resection of the portion of
      phrenic nerve with mass was performed. Grossly, the specimen was a pale-tan piece
      of soft tissue, 4.8 cm in maximum dimension with an attached portion of nerve.
      Microscopically, it showed a well-circumscribed spindle cell lesion with
      hypercellular and hypocellular areas and multiple Verocay bodies. There was no
      atypia or significant mitotic activity. On immunohistochemical staining, the
      spindle cells were positive for S-100, supporting the diagnosis of schwannoma.
      CONCLUSION: Postoperatively, the patient showed marked improvement in his
      symptoms and the hiccups were almost completely resolved. Although they are very
      rare, schwannomas of the phrenic nerve should be considered in the differential
      diagnosis of chronic hiccups.

PMID- 22981785
TI  - Commutability of two JCTLM-listed secondary reference materials for two
      commercial lithium assays.

PMID- 22981786
TI  - Characterization of three new deletions in the beta-globin gene cluster during a
      screening survey in two French urban areas.
AB  - BACKGROUND: Deletions represent about 5% of the mutations in the beta-globin gene
      cluster. We report here the screening for such deletions in the two French urban
      areas of Paris and Lyon between 2003 and 2010. METHODS: Semi-quantitative PCR
      methods were used for the first screening of deletions. Thereafter, a specific
      gap-PCR, eventually followed by DNA sequencing, was used for precise
      identification. RESULTS: 285 patients bore a deletion or recombination event in
      the beta-globin gene cluster. Hbs Lepore or anti-Lepore were detected in 99
      patients. Among the remaining 186 patients, 132 bore a deletion that could be
      fully identified. The most prevalent deletions were the Ghanaian HPFH-2 (n=46),
      the Sicilian (deltabeta)(0)-thal (n=22) and the Spanish (deltabeta)(0)-thal
      (n=12). The other characterized deletions were the: HPFH-3, HPFH-1, Filipino,
      Senegalese, Corfu, Kabilian, -1.39 kb, Indian -619 bp and -468 bp. Interestingly,
      three new deletions were fully characterized: a -7719 bp deletion, a -27,825 bp
      deletion with a 25 bp insertion and a -125 bp deletion. CONCLUSIONS: The present
      study emphasizes the importance to detect deletions in the beta-globin gene
      cluster, particularly for at risk couples. The new -27,825 bp deletion
      illustrates the complexity to understand the transcriptional regulation of fetal
      to adult hemoglobin switch.

PMID- 22981787
TI  - Fel d 1-derived peptide antigen desensitization shows a persistent treatment
      effect 1 year after the start of dosing: a randomized, placebo-controlled study.
AB  - BACKGROUND: Allergic rhinoconjunctivitis is an increasingly common source of
      morbidity, with sensitivity to cats accounting for 10% to 15% of disease burden.
      Allergy to cats is also a major risk factor for the development of asthma.
      OBJECTIVES: We sought to probe the persistence of the treatment effect of a novel
      F el d 1-derived peptide antigen desensitization (Cat-PAD) 1 year after the start
      of treatment in subjects with cat allergy-induced rhinoconjunctivitis after
      standardized allergen challenge. METHODS: In a randomized, double-blind, placebo
      controlled, parallel-group clinical trial, subjects attended an environmental
      exposure chamber in which they were exposed to cat allergen before and after
      treatment with 2 different regimens of Cat-PAD over a 3-month period. Clinical
      efficacy was assessed as a change in total rhinoconjunctivitis symptom scores 18
      to 22 weeks and 50 to 54 weeks after the start of treatment. RESULTS: Treatment
      with Cat-PAD showed greater efficacy with 4 administrations of a 6-nmol dose 4
      weeks apart than with 8 administrations of a 3-nmol dose 2 weeks apart. The
      treatment effect of 6 nmol persisted 1 year after the start of treatment and was
      significantly different from that of 3 nmol (P = .0342) and placebo (P = .0104).
      The treatment effect was apparent on both nasal and ocular symptoms at 1 year.
      CONCLUSIONS: A short course of Cat-PAD improves the ocular and nasal components
      of rhinoconjunctivitis symptoms in subjects with cat allergy, with the treatment
      effect persisting 1 year after the start of treatment.

PMID- 22981789
TI  - Challenges of genetic counseling in patients with autosomal dominant diseases,
      such as the hyper-IgE syndrome (STAT3-HIES).

PMID- 22981788
TI  - Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected
      airway epithelial cells and promotes a type 2 response to infection.
AB  - BACKGROUND: Respiratory viral infection, including respiratory syncytial virus
      (RSV) and rhinovirus, has been linked to respiratory disease in pediatric
      patients, including severe acute bronchiolitis and asthma exacerbation.
      OBJECTIVE: The study examined the role of the epithelial-derived cytokine thymic
      stromal lymphopoietin (TSLP) in the response to RSV infection. METHODS: Infection
      of human airway epithelial cells was used to examine TSLP induction after RSV
      infection. Air-liquid interface cultures from healthy children and children with
      asthma were also tested for TSLP production after infection. Finally, a mouse
      model was used to directly test the role of TSLP signaling in the response to RSV
      infection. RESULTS: Infection of airway epithelial cells with RSV led to the
      production of TSLP via activation of an innate signaling pathway that involved
      retinoic acid induced gene I, interferon promoter-stimulating factor 1, and
      nuclear factor-kappaB. Consistent with this observation, airway epithelial cells
      from asthmatic children a produced significantly greater levels of TSLP after RSV
      infection than cells from healthy children. In mouse models, RSV-induced TSLP
      expression was found to be critical for the development of immunopathology.
      CONCLUSION: These findings suggest that RSV can use an innate antiviral signaling
      pathway to drive a potentially nonproductive immune response and has important
      implications for the role of TSLP in viral immune responses in general.

PMID- 22981790
TI  - LRBA gene deletion in a patient presenting with autoimmunity without
      hypogammaglobulinemia.

PMID- 22981791
TI  - Deficient antiviral immune responses in childhood: distinct roles of atopy and
      asthma.
AB  - BACKGROUND: Impaired immune response to viral infections in atopic asthmatic
      patients has been recently reported and debated. Whether this condition is
      present in childhood and whether it is affected by atopy per se deserves further
      investigation. OBJECTIVE: We sought to investigate airway interferon production
      in response to rhinovirus infection in children who are asthmatic, atopic, or
      both and its correlation with the airway inflammatory profile. METHODS: Bronchial
      biopsy specimens and epithelial cells were obtained from 47 children (mean age, 5
      +/- 0.5 years) undergoing bronchoscopy. The study population included asthmatic
      children who were either atopic or nonatopic, atopic children without asthma, and
      children without atopy or asthma. Rhinovirus type 16 induction of IFN-lambda and
      IFN-beta mRNA and protein levels was assessed in bronchial epithelial cell
      cultures. The immunoinflammatory profile was evaluated by means of
      immunohistochemistry in bronchial biopsy specimens. RESULTS: Rhinovirus type 16
      induced interferon production was significantly reduced in atopic asthmatic,
      nonatopic asthmatic, and atopic nonasthmatic children compared with that seen in
      nonatopic nonasthmatic children (all P < .05). Increased rhinovirus viral RNA
      levels paralleled this deficient interferon induction. Additionally, IFN-lambda
      and IFN-beta induction correlated inversely with the airway T(H)2
      immunopathologic profile (eosinophilia and IL-4 positivity: P < .05 and r = -0.38
      and P < .05 and r = -0.58, respectively) and with epithelial damage (P < .05 and
      r = -0.55). Furthermore, total serum IgE levels correlated negatively with
      rhinovirus-induced IFN-lambda mRNA levels (P < .05 and r = -0.41) and positively
      with rhinovirus viral RNA levels (P < .05 and r = 0.44). CONCLUSIONS: Deficient
      interferon responses to rhinovirus infection are present in childhood in
      asthmatic subjects irrespective of their atopic status and in atopic patients
      without asthma. These findings suggest that deficient immune responses to viral
      infections are not limited to patients with atopic asthma but are present in
      those with other T(H)2-oriented conditions.

PMID- 22981792
TI  - Spleen tyrosine kinase inhibition attenuates airway hyperresponsiveness and
      pollution-induced enhanced airway response in a chronic mouse model of asthma.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease characterized by airways
      hyperresponsiveness (AHR), reversible airflow obstruction, airway remodeling, and
      episodic exacerbations caused by air pollutants, such as particulate matter (PM;
      PM <2.5 MUm in diameter [PM(2.5)]) and ozone (O(3)). Spleen tyrosine kinase
      (Syk), an immunoregulatory kinase, has been implicated in the pathogenesis of
      asthma. OBJECTIVE: We sought to evaluate the effect of Syk inhibition on AHR in a
      chronic mouse model of allergic airways inflammation and pollutant exposure.
      METHODS: We used a 12-week chronic ovalbumin (OVA) sensitization and challenge
      mouse model of airways inflammation followed by exposure to PM(2.5) plus O(3).
      Respiratory mechanics and methacholine (MCh) responsiveness were assessed by
      using the flexiVent system. The Syk inhibitor NVP-QAB-205 was nebulized
      intratracheally by using a treatment-based protocol 15 minutes before assessment
      of MCh responsiveness. RESULTS: Syk expression increased significantly in the
      airway epithelia of OVA-sensitized and OVA-challenged (OVA/OVA) mice compared
      with OVA-sensitized but PBS-challenged (OVA/PBS) control mice. OVA/OVA mice
      exhibited AHR to MCh, which was attenuated by a single administration of NVP-QAB
      205 (0.3 and 3 mg/kg). PM(2.5) plus O(3) significantly augmented AHR to MCh in
      the OVA/OVA mice, which was abrogated by NVP-QAB-205. Total inflammatory cell
      counts were significantly higher in the bronchoalveolar lavage fluid from OVA/OVA
      than OVA/PBS mice and were unaffected by PM(2.5) plus O(3) or NVP-QAB-205.
      CONCLUSION: NVP-QAB-205 reduced AHR and the enhanced response to PM(2.5) plus
      O(3) to normal levels in an established model of chronic allergic airways
      inflammation, suggesting that Syk inhibitors have promise as a therapy for
      asthma.

PMID- 22981794
TI  - [Combined approach of laparoscopic and open surgery for complex renal lesions].
AB  - OBJECTIVE: To develop a combined surgical approach (laparoscopic and open) that
      allows an increased vascular control and decreased ischemia time, maintaining the
      advantages of pure laparoscopic partial nephrectomy (LPN). MATERIAL AND METHODS:
      During the laparoscopic phase, dissection of the kidney and its pedicle is
      achieved. Then, an open approach is initiated through a mini-laparotomy, with the
      kidney being brought to the incision, improving the identification and exposition
      of the tumors. Following tumor identification by ultrasound, exeresis of the
      lesion is performed with or without vascular clamping. RESULTS: Through this
      approach we performed the excision of complex lesions in 6 patients. Mean
      surgical time was 192 minutes (range 180-210) and mean warm ischemia time was 13
      minutes (0-22), with a mean blood loss of 267 mL (100-500). Average pre and
      postoperative glomerular filtration rate was 51.5 (28-90) and 48.8 mL/min/1.73
      m(2) (19-90), respectively. In one patient, suture repair of the pelvicaliceal
      system was needed, with no other perioperative morbidities being reported.
      CONCLUSIONS: This combined approach is a minimally invasive surgical alternative,
      reproducible and safe which preserves the virtues of pure LPN. It allows a better
      control of the vascular pedicle, reducing the risk of hemorrhage and the warm
      ischemia time. This technique may be either considered in the treatment of renal
      masses with indication for partial nephrectomy but of complex laparoscopic
      approach or as a surgical approach in the early learning curve of the LPN.

PMID- 22981793
TI  - Phenotypic characterization of lung macrophages in asthmatic patients:
      overexpression of CCL17.
AB  - BACKGROUND: Studies with monocyte-derived macrophages (MDMs) and animal models
      have suggested a role for alternatively activated (M2) macrophages in asthmatic
      inflammation, but in vivo evidence for this phenotype in human asthma is lacking.
      OBJECTIVE: To characterize the phenotype of lung macrophages from asthmatic
      patients in relation to disease severity and treatment. METHODS: M2 biomarkers
      were first identified by using MDMs exposed to T(H)2 cytokines and then used to
      phenotype sputum and bronchoalveolar lavage (BAL) macrophages from 12 healthy
      control subjects, 12 patients with mild asthma, and 14 patients with moderate
      asthma and to assess the effects of corticosteroids and phosphatidylinositol 3
      kinase (PI3K) inhibitors. RESULTS: Sputum macrophages from asthmatic patients
      expressed significantly more CCL17 mRNA but less CD163 than macrophages from
      healthy subjects. However, none of the other M2 biomarkers were differentially
      expressed in asthmatic patients, and ex vivo BAL cells spontaneously produced
      similar amounts of M2 cytokines/chemokines (IL-10, CCL17, and CCL22). CCL17 mRNA
      overexpression correlated weakly but significantly with sputum eosinophilia (P =
      .0252) and was also observed in macrophages from patients with moderate asthma
      treated with inhaled steroids, suggesting relative insensitivity to inhibition by
      corticosteroids. The PI3K inhibitor LY294002 inhibited basal CCL17 release from
      BAL cells and IL-4-stimulated release from MDMs. CONCLUSIONS: This study does not
      support the existence in human asthma of the full M2 phenotype described to date
      but points to upregulation of CCL17 in both patients with mild and those with
      moderate asthma, providing a further source for this ligand of CCR4(+) cells that
      contributes to airways inflammation. CCL17 expression is corticosteroid resistant
      but suppressed by PI3K enzyme inhibitors.

PMID- 22981795
TI  - In situ high throughput method for H(2)S detection during micro-scale wine
      fermentation.
AB  - An in situ high throughput method for the detection of H(2)S during fermentation
      was developed. The method utilizes a redox reaction in which sulfide ion reduces
      methylene blue, leading to its decolourisation. Incorporation of methylene blue
      into the fermentation media allows real-time detection of H(2)S during
      fermentation and the generation of an H(2)S production profile. Kinetic
      parameters extracted from the H(2)S production profile can be used to
      characterise genetic factors affecting H(2)S production and differentiate between
      environmental conditions affecting it. The method, validated here for
      Saccharomyces cerevisiae, is suited for high throughput screening purposes by
      virtue of its simplicity and the ability to detect H(2)S in micro-scale
      fermentations.

PMID- 22981797
TI  - Development of a porcine deep partial thickness burn model.
AB  - Swine are the preferred animal models to study the effects of burns on dermal
      wound healing. Various studies have been published in which little emphasis was
      placed on minimizing burn variability and inconsistency. We developed a novel
      method to create deep partial thickness burns that are highly consistent. A
      custom-made burn device was fabricated to control the pressure applied on the
      swine skin during burn creation. Cylindrical brass blocks, measuring 3 cm in
      diameter, are used to create the burns. A stainless steel post extends from the
      block for insertion into the device holder. In this study, burns were created in
      four female Yorkshire swine. Heating of the brass blocks was conducted using a
      boiling azeotropic solution of 80% polyethylene glycol (PEG) and 20% water and
      boiling water alone. Contact times ranging from 12 to 20 s were used. At 24 h and
      7 d post-injury, two swine were euthanized and tissues collected for digital
      image evaluation and histological assessment using Gomori trichrome staining.
      Digital image analysis showed inconsistent healing in burns created using boiling
      water as compared to the boiling PEG:H(2)O solution. Additionally, histological
      analyses showed that burns created using boiling water were superficial and more
      variable compared to those created using the boiling PEG:H(2)O solution. With a
      burn contact time of 20 s, 48.5+/-5.7% tissue damage was demonstrated at 24 h
      when the PEG:H(2)O solution was used, whereas only 11.9+/-1.3% was observed with
      boiling water.

PMID- 22981796
TI  - Validation of an in vitro exposure system for toxicity assessment of air
      delivered nanomaterials.
AB  - To overcome the limitations of in vitro exposure of submerged lung cells to
      nanoparticles (NPs), we validated an integrated low flow system capable of
      generating and depositing airborne NPs directly onto cells at an air-liquid
      interface (ALI). The in vitro exposure system was shown to provide uniform and
      controlled dosing of particles with 70.3% efficiency to epithelial cells grown on
      transwells. This system delivered a continuous airborne exposure of NPs to lung
      cells without loss of cell viability in repeated 4h exposure periods. We
      sequentially exposed cells to air-delivered copper (Cu) NPs in vitro to compare
      toxicity results to our prior in vivo inhalation studies. The evaluation of
      cellular dosimetry indicated that a large amount of Cu was taken up, dissolved
      and released into the basolateral medium (62% of total mass). Exposure to Cu NPs
      decreased cell viability to 73% (p<0.01) and significantly (p<0.05) elevated
      levels of lactate dehydrogenase, intracellular reactive oxygen species and
      interleukin-8 that mirrored our findings from subacute in vivo inhalation studies
      in mice. Our results show that this exposure system is useful for screening of NP
      toxicity in a manner that represents cellular responses of the pulmonary
      epithelium in vivo.

PMID- 22981798
TI  - Factors associated with mortality and length of stay in the Oporto burn unit
      (2006-2009).
AB  - Retrospective studies are essential to evaluate and improve the efficiency of
      care of burned patients. This study analyses the work done in the burn unit of
      Hospital de S. Joao in the north of Portugal. A retrospective review was
      performed in patients admitted from 2006 to 2009. The study population was
      characterised regarding patient demographics, admissions profile, burn aetiology,
      burn site, extension and treatment. Multiple linear and logistic regression
      models were done in order to elucidate which of these factors influenced the
      mortality and length of stay. The characteristics before and after the creation
      of the burn unit, as well as the similarities and differences with the published
      data of other national and international burn units, are analysed.

PMID- 22981799
TI  - A survey on the current status of burn rehabilitation services in China.
AB  - BACKGROUND: In China, there is a very long history of burn wound treatment, but
      the specialised burn care units were set up only from 1958. With more than 50
      years of practice, great achievements have been made in burn wound care and
      operations in the country. However, in terms of burn rehabilitation, the
      development appears to be slow. In order to determine the current status of burn
      rehabilitation services in China, a survey was conducted to various burn centres
      in China. METHODS: A comprehensive survey was conducted as well as to collect
      data related to (1) the admissions and staffing of the burn centres; (2)
      availability of rehabilitation services, number and educational background of
      specialised personnel dedicated in burn rehabilitation therapy; and (3) the
      difficulties leading to the lag of the burn rehabilitation services. The survey
      was sent to the chiefs of 87 burn centres via e-mail and they were requested to
      fill out the survey questionnaire and to send it back. For those who did not
      respond within 1 month, a reminder was sent. RESULTS: There are totally 39
      (44.8%) burn centres responding to our survey. These centres were geographically
      distributed in nearly 70% of the administrative provinces in China; hence, the
      results could well represent the current burn care system. Most centres have
      recognised the importance of rehabilitation therapy and remarkable improvements
      of outcome in burn patients have been achieved. There are a very huge number of
      burn patients that need rehabilitation therapy, but most centres face the
      problems of shortage of rehabilitation therapists, which apparently could lead to
      the difficulties in delivering a quality rehabilitation programme for patients.
      Although the time of rehabilitation therapy is instituted far earlier than
      before, it is still not widely accepted in the acute burn care stage. There are
      more specialists joining the burn centre and becoming members of the professional
      burn team. However, professional education and training in the burn specialty
      appear to be sparse. There is room for improvement. Problems that impede the
      progress of rehabilitation therapy are: lack of rehabilitation knowledge in
      medical staff as well as the public, the shortage of specialised personnel and
      relatively low educational background of this team, lack of standard guidelines
      for rehabilitation treatment instructions and lack of funding from the
      government. CONCLUSION: After 20 years of clinical practice, rehabilitation
      concepts are well accepted and many forms of rehabilitation techniques are
      carried out in most burn centres that responded to the survey. Yet, the results
      also indicate that there is a short history of rehabilitation practice among the
      burn centres. There is a burning need to enhance the development of
      rehabilitation services so as to meet the demands of management of severely
      burned patients in China. Some suggestions are made to improve the current burn
      rehabilitation services which would include: (1) provide rehabilitation education
      programmes for burn surgeons, therapists, nurses, as well as patients, families
      and the public; (2) set up standard guidelines for clinical instruction of
      rehabilitation therapy; (3) build an interdisciplinary burn team; (4) more
      investigation and research on the physical and psychological outcomes of burn
      patients; and (5) implement administrative measures in terms of staffing, funding
      and offering insurance to burn survivors.

PMID- 22981800
TI  - The effect of TLR4/7 on the TGF-beta-induced Smad signal transduction pathway in
      human keloid.
AB  - BACKGROUND: Keloid formation is closely related with transforming growth factor
      (TGF)-beta-induced Smad signal transduction. Recent studies have shown that toll
      like receptor4 (TLR4) may mediate liver and kidney fibrosis, and activation of
      TLR7 has anti-scarring effect. The role of TLR4/7 signalling in keloid formation,
      however, remains unknown. Our previous tests have found that mute Smad4 inhibited
      scar. We then speculated that keloid may be affected by TLR4/7 through TGF-beta
      induced Smad signal transduction. OBJECTIVES: The aim of this study was to
      evaluate effects of TLR4/7 on the TGF-beta-induced Smad signal transduction
      pathway in human keloid, and provide information for the mechanism and therapy of
      keloid. METHODS: Normal scar samples with normal fibroblasts (NFs) served as
      control samples and keloid samples with keloid fibroblasts (KFs) served as
      experiment samples. Expression of collagen, connective tissue growth factor
      (CTGF), Smad4 and Smad7 and TLR4/7 were tested by immunohistochemistry, reverse
      transcription polymerase chain reaction (PCR) (RT-PCR) and Western blotting,
      respectively. RESULTS: Expression of collagen, CTGF, Smad4 and TLR4 increased
      significantly while expression of Smad7 and TLR7 decreased in KFs while compared
      to NFs in keloid scar group (KFs), which were decreased in the normal scar group
      (NFs). However, expression of Smad7 and TLR7 decreased in the keloid scar group
      (KFs) while compared to the NFs. CONCLUSIONS: TLRs participate in fibrosis of
      scar tissue through the TLRs-TGF-beta-Smads signal pathway. Higher expression of
      TLR4 in keloid increased expression of TGF-beta, CTGF and collagen through the
      Smad4 signal pathway. Activation of TLR7 or Smad7 may inhibit scar formation.

PMID- 22981801
TI  - Roles of exosomes and microvesicles in disease pathogenesis.
AB  - A variety of cells release membrane vesicles, such as exosomes and microvesicles
      (MVs), that are thought to play key roles in cell-cell communication, antigen
      presentation, and the spread of infectious agents throughout the body. There have
      been considerable efforts to use MVs as diagnostic or prognostic markers because
      their composition is reflective of minor physiological changes. Furthermore,
      recent studies demonstrate that MVs derived from infected cells and tumors
      contribute to disease pathogenesis. This review presents an overview of the
      potential roles of MVs with respect to clinical diagnosis and disease
      pathogenesis.

PMID- 22981802
TI  - Clinical outcomes of remnant-preserving augmentation versus double-bundle
      reconstruction in the anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to analyze differences in the clinical
      results between a remnant-preserving augmentation and a double-bundle
      reconstruction. METHODS: Between March 2008 and February 2009, we prospectively
      analyzed 100 cases of anterior cruciate ligament reconstruction with a minimum
      follow-up period of 2 years. There were 55 cases of remnant-preserving
      augmentation and 45 cases of double-bundle reconstruction. We clinically compared
      the preoperative and postoperative range of motion, visual analog scale score,
      Lysholm score, Tegner score, International Knee Documentation Committee knee
      evaluation form score, anterior drawer test, Lachman test, pivot-shift test, KT
      1000 arthrometer (MEDmetric, San Diego, CA) test, and anterior translation on
      Telos stress radiographs (Telos, Weiterstadt, Germany). RESULTS: There were no
      significant differences in the postoperative range of motion, visual analog scale
      score, Lysholm score, Tegner score, and International Knee Documentation
      Committee knee evaluation form score between the 2 groups (P > .05). The anterior
      drawer test was significantly better in the remnant-preserving augmentation group
      than the double-bundle reconstruction group (P = .038). However, there were no
      significant differences in the Lachman test, pivot-shift test, anterior
      translation on Telos stress radiographs, and KT-1000 arthrometer test between the
      2 groups (P > .05). CONCLUSIONS: Clinical outcomes of a remnant-preserving
      augmentation and a double-bundle reconstruction showed similar results in terms
      of anterior and rotary stability and clinical scores. LEVEL OF EVIDENCE: Level
      IV, therapeutic case series.

PMID- 22981803
TI  - Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid
      isolated from Angelica decursiva.
AB  - AIMS OF THE STUDY: We recently reported the potential antioxidant and anti
      inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from
      the whole plants of Angelica decursiva. In this study, we elucidated the anti
      inflammatory mechanisms of UMC in vitro and in vivo. METHODS: The inhibitory
      effects of UMC on the production of nitric oxide (NO), prostaglandin E(2)
      (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha), the expression of nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear
      factor kappa B (NF-kappaB) were evaluated using lipopolysaccharide (LPS)
      stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation
      inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)
      induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of
      UMC was evaluated using carrageenan induced mouse paw edema model. RESULTS: UMC
      dose-dependently inhibited NO and PGE(2) production by down-regulating iNOS and
      COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also
      suppressed the production of the proinflammatory cytokine TNF-alpha in LPS
      stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC
      dose-dependently prevented LPS-induced nuclear translocation of NF-kappaB in RAW
      264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t
      BHP-induced ROS generation in RAW 264.7 cells with an IC(50) value of 705.1
      MUg/ml. Moreover, UMC inhibited lambda-carrageenan induced mouse paw edema by
      70.40 and 60.20% at doses of 50 and 25 mg/kg body weight, respectively.
      CONCLUSION: The combined results of this study indicate that UMC is an important
      anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect
      was due to its ability to inhibit the production of inflammatory mediators via
      inhibition of NF-kappaB activation pathway.

PMID- 22981804
TI  - Benign fibro-osseous lesions: clinicopathologic features from 143 cases diagnosed
      in an oral diagnosis setting.
AB  - OBJECTIVE: The aim of this study was to report the clinicopathologic and
      radiologic features of 143 benign fibro-osseous lesions (BFOLs). STUDY DESIGN:
      Clinical and radiologic information were retrieved from the patients files, and
      histologic features were reviewed from hematoxylin and eosin-stained histologic
      slides. RESULTS: There were 22 ossifying fibromas (OFs), 21 fibrous dysplasias
      (FDs) and 100 osseous dysplasias (ODs; 65 florid, 18 focal, and 17 periapical).
      The mean age of the FD/OF patients was a decade lower than those with OD. The
      mandible was more affected than the maxilla, except in FDs. All FDs and OFs
      presented local swelling, whereas this was observed in <40% of the ODs.
      Radiologic images of the florid/periapical ODs and OFs were predominantly mixed,
      whereas FDs and focal ODs were predominantly radiopaque. CONCLUSIONS: Florid OD,
      OF, and FD were the most common diagnoses, and the clinicopathologic and
      radiologic features were somewhat distinct from the characteristics of other
      populations.

PMID- 22981805
TI  - In silico identification of novel hevein-like peptide precursors.
AB  - Lectins are proteins with ability to bind reversibly and non-enzymatically to a
      specific carbohydrate. They are involved in numerous biological processes and
      show enormous biotechnological potential. Among plant lectins, the hevein domain
      is extremely common, being observed in several kinds of lectins. Moreover, this
      domain is also observed in an important class of antimicrobial peptides named
      hevein-like peptides. Due to higher cysteine residues conservation, hevein-like
      peptides could be mined among the sequence databases. By using the pattern
      CX(4,5)CC[GS]X(2)GXCGX[GST]X(2,3)[FWY]C[GS]X[AGS] novel hevein-like peptide
      precursors were found from three different plants: Oryza sativa, Vitis vinifera
      and Selaginella moellendorffii. In addition, an hevein-like peptide precursor
      from the phytopathogenic fungus Phaeosphaeria nodorum was also identified. The
      molecular models indicate that they have the same scaffold as others, composed of
      an antiparallel beta-sheet and short helices. Nonetheless, the fungal hevein-like
      peptide probably has a different disulfide bond pattern. Despite this difference,
      the complexes between peptide and N,N,N-triacetylglucosamine are stable,
      according to molecular dynamics simulations. This is the first report of an
      hevein-like peptide from an organism outside the plant kingdom. The exact role of
      an hevein-like peptide in the fungal biology must be clarified, while in plants
      they are clearly involved in plant defense. In summary, data here reported clear
      shows that an in silico strategy could lead to the identification of novel hevein
      like peptides that could be used as biotechnological tools in the fields of
      health and agribusiness.

PMID- 22981806
TI  - Neuropeptide FF activates ERK and NF kappa B signal pathways in differentiated SH
      SY5Y cells.
AB  - Neuropeptide FF (NPFF) has been reported to play important roles in regulating
      diverse biological processes. However, little attention has been focused on the
      downstream signal transduction pathway of NPFF. Here, we used the differentiated
      neuroblastoma cell line, dSH-SY5Y, which endogenously expresses hNPFF2 receptor,
      to investigate the signal transduction downstream of NPFF. In particular we
      investigated the regulation of the extracellular signal-regulated protein kinase
      (ERK) and the nuclear factor kappa B (NF-kappaB) pathways by NPFF in these cells.
      NPFF rapidly and transiently stimulated ERK. H89, a selective inhibitor of cyclic
      AMP-dependent protein kinase A (PKA), inhibited the NPFF-activated ERK pathway,
      indicating the involvement of PKA in the NPFF-induced ERK activation. Down
      regulation of nitric oxide synthases also attenuated NPFF-induced ERK activation,
      suggesting that a nitric oxide synthase-dependent pathway is involved. Moreover,
      the core upstream components of the NF-kappaB pathway were also significantly
      activated in response to NPFF, suggesting that the NF-kappaB pathway is involved
      in the signal transduction pathway of NPFF. Collectively, these data demonstrate
      that nitric oxide synthases are involved in the signal transduction pathway of
      NPFF, and provide the first evidence for the interaction between NPFF and the NF
      kappaB pathway. These advances in our interpretation of the NPFF pathway
      mechanism will aid the comprehensive understanding of its function and provide
      novel molecular insight for further study of the NPFF system.

PMID- 22981807
TI  - Evaluation of intraocular pressure elevation in a modified laser-induced glaucoma
      rat model.
AB  - The main drawbacks of currently described pressure induced glaucoma animal models
      are, that intraocular pressure (IOP) either rises slowly, leading to a
      heterogeneous onset of glaucoma in the treated animals or that IOP normalizes
      before significant damage occurs, necessitating re-treatment. Furthermore, a
      variable magnitude of IOP increase often results when particles are introduced
      into the anterior chamber. In order to develop a simple and reproducible rat
      glaucoma model with sustained IOP elevation after a single treatment we induced
      occlusion of the chamber angle by anterior chamber paracentesis and subsequent
      laser coagulation of the limbal area with 35, 40 or 45 laser burns. Right eyes
      served as controls. IOP was measured three times weekly using TonoLab rebound
      tonometry in awake animals. After four weeks, retinal tissue was harvested and
      processed for whole mount preparation. The number of prelabeled, fluorogold
      positive retinal ganglion cells (RGCs) was analyzed under a fluorescence
      microscope. The eyes were further analyzed histologically. Results are expressed
      as means and standard deviation. Amplitude and duration of the IOP elevation
      increased with the number of laser burns. Two weeks after 35, 40 or 45
      translimbal laser burns the IOP difference between treated and control eye was
      7.5 +/- 5, 14 +/- 8 or 19 +/- 9 mmHg, respectively; the RGC density/mm(2) 28 days
      after treatment was 1488 +/- 238 for control eyes (n = 31) and 1514 +/- 287 (n =
      10), 955 +/- 378 (n = 10) or 447 +/- 350 (n = 11) for the respective laser
      groups. Mean IOP of all control eyes over the observation period was 12.4 +/- 0.8
      mmHg. The chamber angle showed pigment accumulation in the trabecular meshwork of
      all laser groups and confluent peripheral anterior synechia after 40 and 45 laser
      burns. Histologic examination of the retina revealed increasing glia activation
      in a pressure dependant manner. In this study, >91% of laser treated rats
      developed secondary glaucoma with sustained IOP elevation for at least 2 weeks.
      The amount of IOP elevation and RGC loss correspond with the number of laser
      burns applied. This relatively high success rate after a single procedure may
      constitutes an advantage over established glaucoma models, as this decreases the
      risk of complications (e.g. corneal decompensation, intraocular bleeding or
      inflammation) and, thus, improves the outcome.

PMID- 22981808
TI  - Brain involvement in glaucoma: advanced neuroimaging for understanding and
      monitoring a new target for therapy.
AB  - On the basis of a large body of experimental data the notion that glaucoma
      damages retinal ganglion cells and central areas of the visual system has been
      put forward. The mechanisms underlying glaucomatous involvement of the central
      areas are not known: the most likely hypothesis is that this event is the result
      of an anterograde transynaptic neurodegeneration triggered by ganglion cells'
      death. However, it is possible that in some cases it may be the consequence of a
      neurodegenerative disease of the central nervous system. In any event, novel
      mechanisms leading to cell demise might be implicated. The development of
      powerful neuroimaging techniques in conjunction with sophisticated analysis has
      recently provided compelling support to the involvement of central stations of
      the visual pathway in patients suffering of glaucoma. Diffusion Tensor-MRI allows
      the central damage associated with glaucoma to be assessed and therapeutic
      efficacy of novel neuroprotective interventions to be quantified.

PMID- 22981809
TI  - Mirror-touch synaesthesia in the phantom limbs of amputees.
AB  - In mirror-touch synaesthesia merely observing another person being touched will
      cause the observers to experience a touch sensation on their own body. The
      current study investigates whether this, normally a developmental condition,
      might be acquired following amputation. Twenty-eight amputees observed 67 videos
      of touch events and indicated a) whether the video elicited tactile sensations,
      b) where on the body this was located, c) the intensity of the sensation, and d)
      whether it was painful. Almost a third of amputees report a tactile sensation on
      their amputated phantom limb when watching someone else being touched. In this
      particular group the sensations tend to be localised on the phantom limb or
      stump, but are rarely reported elsewhere on the body. This occurs irrespective of
      the body part seen. The synaesthetic sensations were more intense when real
      bodies were observed relative to dummies or objects, and when the observed touch
      is mildly painful relative to non-painful. Although frequency, intensity and
      cause of phantom limb pain do not appear to determine whether an amputee will
      report mirror-touch sensations, those who do report it show greater empathic
      emotional reactivity. These results suggest that acquired synaesthesia may be
      linked with sensory loss, arising after amputation, and that highly empathic
      individuals could be predisposed to strengthening existing pathways between
      observed touch and felt touch.

PMID- 22981810
TI  - Developmental differences in hippocampal and cortical contributions to episodic
      retrieval.
AB  - Episodic memory, or the ability to form and retrieve conscious memories about
      specific past events, improves during childhood. Previous adult neuroimaging
      results indicate a central role of the hippocampus in episodic retrieval, but it
      is not clear whether the contribution of the hippocampus changes during
      development. Traditionally, developmental improvements in episodic retrieval have
      been thought to depend on strategic processes mediated by the prefrontal cortex
      (PFC), a region that is considered to have a protracted course of development
      relative to the hippocampus. The primary goal of the present study was to test
      the hypothesis that the development of episodic retrieval is also associated with
      changes in hippocampal function. Children ages 8- to 11-years-old and adults ages
      18-25 (N = 41) encoded black and white line drawings surrounded by either a green
      or red border. Functional magnetic resonance imaging (fMRI) data were acquired
      while participants attempted to recall which colour was originally paired with
      each drawing. Correct recall of item-colour pairings indicated successful
      episodic retrieval. Activity in the anterior hippocampus, but not in the
      posterior hippocampus, was associated with episodic retrieval in adults, whereas
      activity in the posterior, but not in the anterior hippocampus, was associated
      with episodic retrieval in children. Developmental differences were also found in
      regions in anterior lateral PFC and posterior parietal cortex. Overall, these
      results support the view that the development of episodic memory is supported by
      functional changes in the hippocampus as well as in other critical cortical
      regions.

PMID- 22981811
TI  - Abnormal topological organization of structural brain networks in schizophrenia.
AB  - Schizophrenia is a debilitating mental disorder characterized by disturbances of
      thought and emotion as well as neurocognitive deficits. It is hypothesized that
      the core symptoms of schizophrenia arise from the inability to integrate neural
      processes segregated across distributed brain regions. Graph theory allows us to
      verify this hypothesis at large-scale structural network level. In this study, a
      sample of 101 schizophrenic patients and 101 healthy controls was included. We
      sought to investigate the abnormality of network topological organization in
      patients with schizophrenia by using the cortical thickness measurement from
      magnetic resonance imaging. Brain networks were constructed by thresholding
      cortical thickness correlation matrices of 78 regions and analyzed using graph
      theoretical approaches. Compared to healthy controls, patients showed increased
      characteristic path length and clustering coefficient in the structural cortical
      networks. Moreover, schizophrenia patients were associated with reduced nodal
      centrality in several regions of the default network and increased nodal
      centrality mainly in primary cortex and paralimbic cortex regions. These findings
      suggest that the structural networks of schizophrenic patients have a less
      optimal topological organization, resulting in reduced capacity to integrate
      information across brain regions.

PMID- 22981812
TI  - A meta-analysis of the polyunsaturated fatty acid composition of erythrocyte
      membranes in schizophrenia.
AB  - BACKGROUND: Membrane abnormalities in polyunsaturated fatty acids (PUFAs) have
      been reported in schizophrenia and have been associated with brain tissue loss in
      normal ageing. Therefore PUFA may be involved in the excessive brain tissue loss
      reported in schizophrenia. METHODS: A systematic MEDLINE database search was
      conducted to identify studies that compared PUFAs in erythrocyte membranes in
      patients and controls. Patients were categorized by medication regime in
      medication naive first-episode patients, and patients receiving typical or
      atypical antipsychotics. SAMPLE: Fourteen studies were included, comprising a
      total of 429 patients with schizophrenia and 444 healthy control subjects.
      Cohen's d effect sizes were calculated for PUFAs in erythrocyte membranes using
      the random-effects model. Combined Cohen's d was calculated separately for
      patients on different medication regime. RESULTS: Medication-naive patients and
      patients taking typical antipsychotics showed significantly (p<0.01) decreased
      concentrations of arachidonic (AA), docosahexaenoic (DHA), and docosapentaenoic
      (DPA) acid. In addition, patients taking typical antipsychotics showed decreased
      linoleic (LA), dihomo-gamma-linolenic acid (DGLA), eicosapentaenoic (EPA) and
      docosatetraenoic (DTA) acid (p<0.01). Patients taking atypical antipsychotics
      showed decreased DHA (p<0.01) only. CONCLUSIONS: PUFA concentrations in
      erythrocyte membranes are decreased in schizophrenia. Of particular importance in
      patients are lower concentrations of DHA and AA, two fatty acids that are
      abundant in the brain and important precursors in the cell-signalling cascade.

PMID- 22981813
TI  - An assessment of the skin sensitisation hazard of a group of polyfunctional
      silicones using a weight of evidence approach.
AB  - Discordant results were observed when testing five prototype polyfunctional
      silicone materials for skin sensitization potential in the murine local lymph
      node assay (LLNA) and in the guinea pig maximization test (GPMT). While all five
      silicone materials were consistently negative in the GPMT, the testing in the
      LLNA revealed weak to moderate skin sensitisation potential for four of the five
      test materials. Neither study quality nor other known chemical factors could
      explain these findings. Further analysis did not provide sufficient evidence for
      a link between the LLNA responses and the irritancy of the test substances. Only
      in the case of one of the test materials, the occurrence of an excessive level of
      irritation could be linked to the positive LLNA result. Considering all existing
      information including physico-chemical and structure activity and animal data as
      well as existing human experience from silicone exposures at the workplace or
      their use in cosmetic products, the weight of evidence suggests that none of the
      examined silicone materials represents a significant skin sensitization hazard to
      humans. The suitability of the LLNA appears questionable for this class of
      materials. In case of any additional data needs for other or new silicone
      materials, the skin sensitization testing strategy will require careful
      evaluation and will need to be set up on a case by case basis.

PMID- 22981814
TI  - Intravital microscopy: new insights into cellular interactions.
AB  - Inflammation is the body's way of combating invading pathogens or noxious
      stimuli. Under normal conditions, the complex host response of rubor, dolor,
      calor, tumor, and functio laesa is essential for survival and the return to
      homeostasis. However, unregulated inflammation is all too often observed in
      diseases such as rheumatoid arthritis, stroke, and cancer. The host inflammatory
      response is governed by a number of tightly regulated processes that enable
      cellular trafficking to occur at the sites of damage to ultimately ensure the
      resolution of inflammation. Intravital microscopy (IVM) provides quantitative,
      qualitative, and dynamic insights into cell biology and these cellular
      interactions. This review highlights the pros and cons of this specialized
      technique and how it has evolved to help understand the physiology and
      pathophysiology of inflammatory events in a number of different disease states,
      leading to a number of potential therapeutic targets for drug discovery.

PMID- 22981815
TI  - A novel type of paramyxovirus found in Hungary in a masked water snake
      (Homalopsis buccata) with pneumonia supports the suggested new taxonomy within
      the Ferlavirus genus.
AB  - During the course of a longitudinal survey on the occurrence of viruses in
      Hungarian exotic reptile collections a dead masked water snake (Homalopsis
      buccata) was submitted for virologic examination in September 2009. Based on
      history, gross pathological and histopathological findings paramyxovirus
      infection was suspected and later confirmed by RT-PCR and sequencing of the RNA
      dependent RNA polymerase (L), the hemaggluitinin-neuraminidase (HN) and the
      unknown (U) genes. Sequence analyses revealed that the detected virus, HoBuc
      HUN09, belongs to the recently described "group C" within the genus Ferlavirus.
      Our paper presents the first description of this novel reptilian paramyxovirus
      from a homalopsid snake with mucopurulent pneumonia in Hungary.

PMID- 22981816
TI  - The role of galU and galE of Haemophilus parasuis SC096 in serum resistance and
      biofilm formation.
AB  - In our previous study, an ompP2 mutant of a Haemophilus parasuis SC096 strain
      showed sensitivity to serum bactericidal activity. In this study, we inactivated
      two gal genes, galU and galE, and these mutants were found to be serum sensitive
      to porcine sera. Furthermore, the galE mutant exhibited greater sensitivity than
      the galU mutant in serum sensitivity assays. Biofilm formation ability was also
      investigated. The galU mutant is unable to form biofilms, while more biofilm mass
      was produced by the galE mutant compared with SC096. Lack of expression of GalU
      protein by the galU mutant increased its tendency to autoagglutinate. The results
      indicated that the galU plays a role in autoagglutination and biofilm formation,
      while galE may affect the biofilm production indirectly. Both genes are
      significant for serum resistance in the H. parasuis SC096 strain.

PMID- 22981818
TI  - Preparation of chitooligosaccharides from Clanis bilineata larvae skin and their
      antibacterial activity.
AB  - Clanis bilineata larvae are widely consumed in China. In this study,
      chitooligosaccharides were prepared from C. bilineata larvae skin by
      demineralisation, deproteination, washing, drying, deacetylation, hydrolysis
      using commercial alpha-amylase, filtration, setting the preparation at
      approximately 15% (w/v), precipitation with 6 volumes of ethanol, and drying at
      60 degrees C for 2 h. The optimal hydrolysis conditions were determined as
      follows: pH 5.5; temperature, 55 degrees C; enzyme amount, 40 mg/(g chitosan);
      reaction time, 4 h. The Fourier transform infrared spectra revealed that
      chitooligosaccharides with a degree of polymerisation in the range of 2-8 were
      the main component of the resulting product, with the chitooligosaccharide
      content and yield being 95.8% and 96.2% (w/w), respectively. The resulting
      product showed high antibacterial activity compared with the original chitosan.

PMID- 22981817
TI  - Al3+ ion cross-linked interpenetrating polymeric network microbeads from tailored
      natural polysaccharides.
AB  - Interpenetrating network (IPN) microbeads of sodium carboxymethyl locust bean gum
      (SCMLBG) and sodium carboxymethyl cellulose (SCMC) containing diclofenac sodium
      (DS), a non steroidal anti-inflammatory drug were prepared by single water-in
      water (w/w) emulsion gelation process using AlCl(3) as cross-linking agent in a
      complete aqueous environment. The influence of different variables like total
      polymer concentration, gelation time and crosslinker content on in vitro physico
      chemical characteristics and drug release rate in different media was
      investigated. Drug loaded microbeads were evaluated through Fourier transform
      infra-red (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry
      (DSC) analyses. Scanning electron microscopy (SEM) micrograph of the beads
      suggested the formation of spherical particles. FTIR analysis indicated the
      stable nature of the drug in the blend microbeads. DSC and XRD analysis revealed
      amorphous state of drug after encapsulation. The drug release profile in acidic
      medium was considerably less in comparison to alkaline media. Formulations showed
      non-Fickian type transport mechanism. These tri-valent ion crosslinked beads not
      only improve drug encapsulation efficiency but also enhance drug release in
      phosphate buffer.

PMID- 22981819
TI  - Synthesis of thermo-sensitive CS-g-PNIPAM/CMC complex nanoparticles for
      controlled release of 5-FU.
AB  - In this paper, self-assembled thermo-sensitive polyelectrolyte complex
      nanoparticles formed from chitosan-graft-poly(N
      isopropylacrylamide)/carboxymethyl cellulose (CS-g-PNIPAM/CMC) were prepared for
      entrapment and release of 5-fluorouracil (5-FU). The morphology and size of the
      nanoparticles were observed by transmission electron microscopy (TEM) and dynamic
      light scattering (DLS). The polyelectrolyte complex nanoparticles showed a narrow
      distribution with an average diameter of about 200 nm. The hydrogen bonding
      interaction between nanoparticles and 5-FU was determined by Fourier-transformed
      infrared spectroscopy (FTIR). Increasing temperature or pH of the solutions, a
      sustained and controlled drug release was observed. The chemical cross-linking
      was an efficient way to decrease the drug release rate at the initial stage. The
      novel complex nanoparticles with environmentally sensitive properties are
      expected to be used in the field of intelligent drug delivery system.

PMID- 22981820
TI  - Altered serum stress neuropeptide levels in critically ill individuals and
      associations with lymphocyte populations.
AB  - OBJECTIVE: Potential physiological correlates of stress and the role of stress
      neuropeptides, other than those of the hypothalamic-pituitary-adrenal axis, in
      critical illness have not been addressed. We investigated: (a) serum levels of
      stress neuropeptides (ACTH, substance P (SP), neuropeptide Y (NPY), cortisol,
      prolactin) in critically ill individuals compared to matched controls, (b)
      associations with lymphocyte counts, (c) associations among stress neuropeptide
      levels, and (d) associations with perceived intensity of stress, critical illness
      severity and survival. METHODS: Correlational design with repeated measures.
      Thirty-six critically ill patients were followed up for 14 days compared to 36
      healthy matched controls. Stress was assessed by the ICUESS scale. Correlations,
      cross-sectional comparisons and multiple regression models were pursued. RESULTS:
      For the first time, we report lower SP (Difference of means (DM) = 2928-3286
      ng/ml, p < 0.001) and NPY (DM = 0.77-0.83 ng/ml, p < 0.0001) levels in critically
      ill individuals compared to controls. Cortisol levels were higher (DM = 140-173
      ng/ml, p<0.0001) and lymphocyte population counts (p < 0.002) were lower in
      patients throughout the study. NPY levels associated with lymphocyte (r = 0.411
      0.664, p < 0.04), T-lymphocyte (r = 0.403-0.781, p< 0.05), T-helper (r = 0.492
      0.690, p < 0.03) and T-cytotoxic cell populations (r = 0.39-0.740, p < 0.03). On
      day 1, cortisol levels exhibited associations with lymphocyte (r = -0.452, p =
      0.01), T-cell (r = -0.446, p = 0.02), T-helper (r = -0.428, p = 0.026) and T
      cytotoxic cells ( r = -0.426, p = 0.027). ACTH levels associated with NK cell
      counts (r = 0.326-0.441, p < 0.05). Associations among stress neuropeptides
      levels were observed throughout (p < 0.05). ACTH levels associated with disease
      severity (r = 0.340-0.387, p < 0.005). A trend for an association between ACTH
      levels and intensity of stress was noted (r = 0.340, p = 0.057). CONCLUSION: The
      significantly lowered NPY and SP levels and the associations with cortisol, ACTH
      and lymphocytes suggest that the role of these peptides in critical illness merit
      further investigation. Future studies need to address associations between these
      neuropeptides and functional immune cell responses and inflammatory markers in
      critical illness.

PMID- 22981821
TI  - Fat and carbohydrate metabolism during exercise in late-onset Pompe disease.
AB  - Pompe disease is caused by absence of the lysosomal enzyme acid alpha
      glucosidase. It is generally assumed that intra-lysosomal hydrolysis of glycogen
      does not contribute to skeletal muscle energy production during exercise.
      However, this hypothesis has never been tested in vivo during exercise. We
      examined the metabolic response to exercise in patients with late-onset Pompe
      disease, in order to determine if a defect in energy metabolism may play a role
      in the pathogenesis of Pompe disease. We studied six adult patients with Pompe
      disease and 10 healthy subjects. The participants underwent ischemic forearm
      exercise testing, and peak work capacity was determined. Fat and carbohydrate
      metabolism during cycle exercise was examined with a combination of indirect
      calorimetry and stable isotope methodology. Finally, the effects of an IV glucose
      infusion on heart rate, ratings of perceived exertion, and work capacity during
      exercise were determined. We found that peak oxidative capacity was reduced in
      the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002).
      There were no differences in the rate of appearance and rate of oxidation of
      palmitate, or total fat and carbohydrate oxidation, between the patients and the
      healthy subjects. None of the subjects improved exercise tolerance by IV glucose
      infusion. In conclusion, peak oxidative capacity is reduced in Pompe disease.
      However, skeletal muscle fat and carbohydrate use during exercise was normal. The
      results indicate that a reduced exercise capacity is caused by muscle weakness
      and wasting, rather than by an impaired skeletal muscle glycogenolytic capacity.
      Thus, it appears that acid alpha-glucosidase does not play a significant role in
      the production of energy in skeletal muscle during exercise.

PMID- 22981822
TI  - Carotid artery image segmentation using modified spatial fuzzy c-means and
      ensemble clustering.
AB  - Disease diagnosis based on ultrasound imaging is popular because of its non
      invasive nature. However, ultrasound imaging system produces low quality images
      due to the presence of spackle noise and wave interferences. This shortcoming
      requires a considerable effort from experts to diagnose a disease from the
      carotid artery ultrasound images. Image segmentation is one of the techniques,
      which can help efficiently in diagnosing a disease from the carotid artery
      ultrasound images. Most of the pixels in an image are highly correlated.
      Considering the spatial information of surrounding pixels in the process of image
      segmentation may further improve the results. When data is highly correlated, one
      pixel may belong to more than one clusters with different degree of membership.
      In this paper, we present an image segmentation technique namely improved spatial
      fuzzy c-means and an ensemble clustering approach for carotid artery ultrasound
      images to identify the presence of plaque. Spatial, wavelets and gray level co
      occurrence matrix (GLCM) features are extracted from carotid artery ultrasound
      images. Redundant and less important features are removed from the features set
      using genetic search process. Finally, segmentation process is performed on
      optimal or reduced features. Ensemble clustering with reduced feature set
      outperforms with respect to segmentation time as well as clustering accuracy.
      Intima-media thickness (IMT) is measured from the images segmented by the
      proposed approach. Based on IMT measured values, Multi-Layer Back-Propagation
      Neural Networks (MLBPNN) is used to classify the images into normal or abnormal.
      Experimental results show the learning capability of MLBPNN classifier and
      validate the effectiveness of our proposed technique. The proposed approach of
      segmentation and classification of carotid artery ultrasound images seems to be
      very useful for detection of plaque in carotid artery.

PMID- 22981824
TI  - Chitin extraction from shrimp shell waste using Bacillus bacteria.
AB  - The ability of six protease-producing Bacillus species (Bacillus pumilus A1,
      Bacillus mojavencis A21, Bacillus licheniformis RP1, Bacillus cereus SV1,
      Bacillus amyloliquefaciens An6 and Bacillus subtilis A26) to ferment media
      containing only shrimp shell waste, for chitin extraction, was investigated. More
      than 80% deproteinization was attained by all the strains tested. However,
      demineralization rates not exceeding 67% were registered. Cultures conducted in
      media containing shrimp shell waste supplemented with 5% (w/v) glucose were found
      to remarkably promote demineralization efficiency, without affecting
      deproteinization rates. The antioxidant activities of hydrolysates, at different
      concentrations, produced during fermentation in medium supplemented with glucose,
      were determined using different tests: 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical-scavenging method, reducing power assay and chelating activity. All
      hydrolysates showed varying degrees of antioxidant activity. Hydrolysate produced
      by B. pumilus A1 exhibited the highest DPPH radical scavenging activity, with an
      IC(50) value of 0.3 mg/ml. Highest reducing power (DO 700 nm=1.55 at 1.5 mg/ml)
      and metal chelating activity (98% at 5mg/ml) were obtained with B. pumilus A1 and
      B. licheniformis RP1 hydrolysates, respectively.

PMID- 22981823
TI  - Epigenomic annotation of enhancers predicts transcriptional regulators of human
      neural crest.
AB  - Neural crest cells (NCC) are a transient, embryonic cell population characterized
      by unusual migratory ability and developmental plasticity. To annotate and
      characterize cis-regulatory elements utilized by the human NCC, we coupled a hESC
      differentiation model with genome-wide profiling of histone modifications and of
      coactivator and transcription factor (TF) occupancy. Sequence analysis predicted
      major TFs binding at epigenomically annotated hNCC enhancers, including a master
      NC regulator, TFAP2A, and nuclear receptors NR2F1 and NR2F2. Although many TF
      binding events occur outside enhancers, sites coinciding with enhancer chromatin
      signatures show significantly higher sequence constraint, nucleosomal depletion,
      correlation with gene expression, and functional conservation in NCC isolated
      from chicken embryos. Simultaneous co-occupancy by TFAP2A and NR2F1/F2 is
      associated with permissive enhancer chromatin states, characterized by high
      levels of p300 and H3K27ac. Our results provide global insights into human NC
      chromatin landscapes and a rich resource for studies of craniofacial development
      and disease.

PMID- 22981825
TI  - Enhanced delivery of baicalein using cinnamaldehyde cross-linked chitosan
      nanoparticle inducing apoptosis.
AB  - The chitosan (CS) nanoparticles, baicalein loaded chitosan nanoparticles were
      prepared by crosslinking method in a W/O emulsion system, using cinnamaldehyde as
      crosslinking agent. The FT-IR result showed the binding of anticancer compound
      baicalein to the nanoparticles. The TEM analysis revealed that the particles are
      spherical in nature. Zeta potential revealed negative charge of the particles.
      Ultraviolet spectrum analysis described that higher loading efficiency and
      encapsulation efficiency as 9.1% and 97.2%, respectively. In vitro baicalein
      release profile demonstrated the delivery of baicalein from the CS nanoparticles
      is a two stage process. RT-PCR and cell culture was carried out accordingly.

PMID- 22981826
TI  - Physiochemical and optical study of chitosan-terephthaldehyde derivative for
      biomedical applications.
AB  - The chitosan-terephthaldehyde derivative was prepared by conversion of the
      chitosan gels through the extraction of the solvent, filtration and drying, a
      greener technique used for processing the materials. The identity of Schiff base
      was confirmed by UV-vis and Fourier-transform infrared (FTIR) spectroscopy. The
      chitosan-terephthaldehyde derivative was evaluated by X-ray diffraction (XRD),
      thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),
      scanning electron microscopy (SEM), photoluminescence (PL) and rheological study.
      Photoluminescence (PL) spectrum had shown red shifted at excitation wavelength
      254 nm. The rheological study revealed satisfactory behaviour which demonstrates
      better fluidity as well as moderate viscoelastic strength of the prepared gel.
      These results suggest that the chitosan-terephthaldehyde derivative material may
      open a new perspective in biomedical applications.

PMID- 22981827
TI  - Enhancement of poly(3-hydroxybutyrate) thermal and processing stability using a
      bio-waste derived additive.
AB  - Poly(3-hydroxybutyrate) (PHB) is a biodegradable polymer, whose applicability is
      limited by its brittleness and narrow processing window. In this study a pomace
      extract (EP), from the bio-waste of winery industry, was used as thermal and
      processing stabilizer for PHB, aimed to engineer a totally bio-based system. The
      results showed that EP enhanced the thermal stability of PHB, which maintained
      high molecular weights after processing. This evidence was in agreement with the
      slower decrease in viscosity over time observed by rheological tests. EP also
      affected the melt crystallization kinetics and the overall crystallinity extent.
      Finally, dynamic mechanical and tensile tests showed that EP slightly improved
      the polymer ductility. The results are intriguing, in view of the development of
      sustainable alternatives to synthetic polymer additives, thus increasing the
      applicability of bio-based materials. Moreover, the reported results demonstrated
      the feasibility of the conversion of an agro-food by-product into a bio-resource
      in an environmentally friendly and cost-effective way.

PMID- 22981829
TI  - [Comment to the work "Are there differences in the neurosurgical management of
      intracranial lesions in pregnant patients? Outcomes of our experience and
      literature review" by Caminero-Canas et al].

PMID- 22981828
TI  - HIV-1 antibodies from infection and vaccination: insights for guiding vaccine
      design.
AB  - Attempts to formulate a protective HIV-1 vaccine through classic vaccine design
      strategies have not been successful. Elicitation of HIV-1-specific broadly
      neutralizing antibodies (bnAbs) at high titers that are present before exposure
      might be required to achieve protection. Recently, the application of new
      technologies has facilitated the study of clonal lineages of HIV-1 envelope (Env)
      antibodies, which have provided insights into HIV-1 antibody development during
      infection and upon vaccination. Strategies are being developed for the analysis
      of infection and vaccine candidate-induced antibodies, their gene usage, and
      their maturation pathways such that this information can be used to attempt to
      guide rational vaccine design.

PMID- 22981830
TI  - The effects of bisphenol A (BPA) exposure on fat mass and serum leptin
      concentrations have no impact on bone mineral densities in non-obese
      premenopausal women.
AB  - OBJECTIVES: Bisphenol A (BPA) exposure may promote obesity, but its effect on
      bone mineral density (BMD) has not been reported in humans. We aimed to examine
      the relationships between BPA exposure, body composition, serum estradiol,
      leptin, osteocalcin levels and BMDs in healthy premenopausal women. DESIGN AND
      METHODS: In this cross-sectional study, a total of 246 healthy premenopausal
      women aged 20 years and older with regular menstrual cycles were investigated.
      Body mass index (BMI), fat mass, fat-free mass and BMDs were measured by DXA.
      Serum estradiol, leptin, osteocalcin, urinary BPA and NTx levels were also
      tested. RESULTS: Urinary BPA levels were positively associated with fat mass
      (r=0.193, p=0.006) and leptin (r=0.236, p=0.001) but not with fat-free mass after
      adjusting for age and BMI. BPA was not associated with serum estradiol levels,
      BMDs, or bone resorption marker NTx and bone formation parameter osteocalcin,
      either. A multivariate stepwise regression analysis confirmed that serum leptin
      levels were positively influenced by fat mass (beta=0.746, p<0.001) and BPA
      (beta=0.127, p=0.01) but negatively correlated with fat-free mass (beta=-0.196,
      p<0.001). However, the changes of BMDs at the lumbar spine (beta=0.298, p<0.001)
      and femoral neck (beta=0.305, p<0.001) were primarily explained by fat-free mass,
      and were irrelevant of the fat mass, leptin or BPA exposure. CONCLUSIONS:
      Although BPA exposure is related with increased amount of fat mass and elevated
      serum leptin levels, it has neutral effect on BMDs in premenopausal women,
      possibly due to the exclusive role of fat-free mass, which is unrelated to BPA in
      determining BMDs.

PMID- 22981831
TI  - Antioxidative properties of hydrogen sulfide may involve in its antiadhesive
      action on blood platelets.
AB  - BACKGROUND: Hydrogen sulfide (H(2)S) is a signaling molecule in different
      systems, including the cardiovascular system. However, mechanisms involved in the
      relationship between the action of H(2)S and hemostasis process are still
      unclear. OBJECTIVE AND METHODS: The present work was designed to study the
      effects of hydrogen sulfide on adhesion of blood platelets in vitro. Platelet
      suspensions were preincubated (5-30 min) with NaHS as a hydrogen sulfide donor at
      the final concentrations of 0.00001-10 mM. Then, for platelet activation thrombin
      (0.1 U/mL) or TRAP, peptide with the sequence Ser-Phe-Leu-Leu-Arg-Asn (SFLLRN; 20
      MUM) was used. We also measured the effects of H(2)S on superoxide anion radicals
      (O(2)(-*)) production in blood platelets. RESULTS: We observed that adhesion to
      collagen and to fibrinogen of resting platelets preincubated with NaHS was
      changed, and this process was statistically significant (for 0.00001-5mM NaHS,
      p<0.05; 10 mM, p<0.01). The inhibitory effect of NaHS on adhesion of thrombin -
      or TRAP - stimulated platelets to collagen was found (for 0.00001 and 0.0001 mM
      NaHS, p<0.05; 0.001-1 mM NaHS, p<0.01; 5 and 10 mM NaHS, p<0.001). Hydrogen
      sulfide reduced also the thrombin- or TRAP-induced platelet adhesion to
      fibrinogen (for 0.00001 and 0.0001 mM NaHS, p<0.05; 0.001-1 mM NaHS, p<0.01; 5
      and 10 mM NaHS, p<0.001). Moreover, H(2)S caused a dose-dependent reduction of
      O(2)(-*) produced in platelets (p<0.05). CONCLUSION: The results obtained that
      the antioxidative activity of H(2)S may involve in its antiadhesive properties on
      blood platelets.

PMID- 22981833
TI  - A new controlled concept of immune-sensing platform for specific detection of
      Alzheimer's biomarkers.
AB  - We propose a concept of very specific immune-sensing platform dedicated to the
      quantification of biomarkers of Alzheimer disease (AD) in biological fluids. High
      sensitivity is required for the earliness of AD diagnostic, mainly based on
      clinical evaluation at present time. Accordingly, a controlled and adaptative
      surface functionalization of a silicon wafer with carboxylated
      alkyltrichlorosilane has been developed. The surface has extensively been
      characterized by AFM and X-ray Photoemissive Spectroscopy. The surface
      modification has been chemically assessed by XPS at each functionalization step.
      The survey spectra of silicon surface, after, 1, 3, 6 and 24 h of silanisation,
      highlight a significant enhancement of the functionalization efficiency upon
      time. The oxidation reaction has also been investigated by XPS and showed
      components related to the carboxylic group. AFM measurements pointed out a
      morphological modification consistent with a homogenous development of the
      carboxylic group and an almost protein monolayer on the surface. Moreover, we
      evaluated the biological activity of the grafted antibodies involved in (AD)
      biomarker detection onto this silanized surface by fluorescent microscopy. A
      sandwich immunoassay dedicated to the sensitive detection of one biomarker of
      Alzheimer disease (AD), the amyloid peptide 1-42 (Abeta 1-42), was carried out.
      The results demonstrated that the controlled silanized surface provides a novel
      and viable way to detect biomarkers with high specificity and open the route to
      an original development of immune-sensing applications on such surfaces.

PMID- 22981832
TI  - Effects of salinity acclimation on the pesticide-metabolizing enzyme flavin
      containing monooxygenase (FMO) in rainbow trout (Oncorhynchus mykiss).
AB  - Thioether-containing pesticides are more toxic in certain anadromous and
      catadromous fish species that have undergone acclimation to hypersaline
      environments. Enhanced toxicity has been shown to be mediated through the
      bioactivation of these xenobiotics by one or more flavin-containing
      monooxygenases (FMOs), which are induced by hyperosmotic conditions. To better
      understand the number of FMO genes that may be regulated by hyperosmotic
      conditions, rainbow trout (Oncorhynchus mykiss) were maintained and acclimated to
      freshwater (<0.5 g/L salinity) and to 18 g/L salinity. The expression of 3
      different FMO transcripts (A, B and C) and associated enzymatic activities methyl
      p-tolyl sulfoxidation (MTSO) and benzydamine N-oxigenation (BZNO) were measured
      in four tissues. In freshwater-acclimated organisms FMO catalytic activities were
      as follows: liver>kidney>gills=olfactory tissues; in hypersaline-acclimated
      animals activities were higher in liver>gills>olfactory tissues>kidney.
      Acclimation to 18 g/L caused a significant induction in the stereoselective
      formation of R-MTSO in gill. In olfactory tissues, stereoselective (100%)
      formation of S-MTSO was observed and was unaltered by acclimation to hypersaline
      water. When specific transcripts were evaluated, salinity-acclimation increased
      FMO A in liver (up to 2-fold) and kidney (up to 3-fold) but not in olfactory
      tissues and gills. FMO B mRNA was significantly down-regulated in all tissues,
      and FMO C was unchanged by hypersaline acclimation. FMO B and C failed to
      correlate with any FMO catalytic activity, but FMO A mRNA expression linearly
      correlated to both FMO catalytic activities (MTSO and BZNO) in liver (r(2)=0.92
      and r(2)=0.88) and kidney microsomes (r(2)=0.93 and r(2)=90). FMO A only
      correlated with MTSO activity in gills (r(2)=0.93). These results indicate unique
      tissue specific expression of FMO genes in salmonids and are consistent with
      salinity-mediated enhancement of thioether-containing pesticide bioactivation by
      FMO which may occur in liver or kidney after salinity acclimation.

PMID- 22981834
TI  - Predicting PTSD: pre-existing vulnerabilities in glucocorticoid-signaling and
      implications for preventive interventions.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder that may develop in
      response to a traumatic event. Approximately 10% of trauma-exposed individuals
      subsequently develop PTSD. It is hypothesized that the development of PTSD is
      associated with biological vulnerability factors, which are already present prior
      to the onset of symptoms. In this review we present an overview of currently
      identified vulnerability factors in the glucocorticoid (GC) signaling pathway for
      the development of PTSD. In addition, the implications of the identified
      vulnerability factors for potential preventive intervention strategies, including
      glucocorticoid receptor (GR) agonists and oxytocin, are discussed. Summarized,
      the findings of these studies indicate that individuals vulnerable for
      development of PTSD have dysregulations on various levels of the GC-signaling
      cascade: i.e. low levels of circulating levels of cortisol shortly after trauma,
      high GR number in peripheral blood mononuclear cells (PBMCs), high GILZ mRNA
      expression and low FKBP5 expression in PBMCs prior to trauma, and high
      sensitivity of T-cells for regulation by GCs prior to trauma. Furthermore, single
      nucleotide polymorphisms in the GR and FKBP5 genes have been found to be
      associated with increased risk for PTSD. Collectively, the identified
      vulnerability factors tentatively suggest that the development of PTSD may be
      preceded by a high sensitivity of various cells for regulation by GCs. The
      identification of these vulnerability factors may ultimately aid selective
      targeting of preventive interventions towards individuals at risk for PTSD. In
      addition, the identification of these vulnerability factors may eventually result
      in new preventive pharmacological strategies for PTSD.

PMID- 22981836
TI  - Dissecting the different biological effects of oncogenic Ras isoforms in cancer
      cell lines: could stimulation of oxidative stress be the one more weapon of H
      Ras? Regulation of oxidative stress and Ras biological effects.
AB  - Ras proteins are small GTPase functioning as molecular switches that, in response
      to particular extracellular signalling, as growth factors, activate a diverse
      array of intracellular effector cascades regulating cell proliferation,
      differentiation and apoptosis. Human tumours frequently express Ras proteins (Ha
      , Ki-, N-Ras) activated by point mutations which contribute to malignant
      phenotype, including invasiveness and angiogenesis. Despite the common signalling
      pathways leading to similar cellular responses, studies clearly demonstrate
      unique roles of the Ras family members in normal and pathological conditions and
      the lack of functional redundancy seems to be explainable, at least in part, by
      the ability of Ras isoforms to localize in different microdomains to plasma
      membrane and intracellular organelles. This different intracellular
      compartmentalization could help Ras isoforms to contact different downstream
      effectors finally leading to different biological outcomes. Interestingly, it has
      also been shown that Ha- and Ki-Ras exert an opposite role in regulating
      intracellular redox status. In this regard we suggest that H-Ras specific
      induction of ROS (reactive oxygen species) production could be one of the main
      determinants of the invasive phenotype which characterize cancer cells harbouring
      H-Ras mutations. In our hypothesis then, while K-Ras (not able to promote
      oxidative stress) could mainly contribute to cancer progression and invasiveness
      through activation of MAPK and PI3K, H-Ras-mediated oxidative stress could play a
      unique role in modulation of intercellular contacts leading to a loss of cell
      adhesion and eventually also to a metastatic spread.

PMID- 22981835
TI  - Educational attainment and late life telomere length in the Health, Aging and
      Body Composition Study.
AB  - Morbidity and mortality are greater among socially disadvantaged racial/ethnic
      groups and those of lower socioeconomic status (SES). Greater chronic stress
      exposure in disadvantaged groups may contribute to this by accelerating cellular
      aging, indexed by shorter age-adjusted telomere length. While studies
      consistently relate shorter leukocyte telomere length (LTL) to stress, the few
      studies, mostly from the UK, examining associations of LTL with SES have been
      mixed. The current study examined associations between educational attainment and
      LTL among 2599 high-functioning black and white adults age 70-79 from the Health,
      Aging and Body Composition Study. Multiple regression analyses tested
      associations of race/ethnicity, educational attainment and income with LTL,
      adjusting for potential confounders. Those with only a high school education had
      significantly shorter mean LTL (4806 basepairs) than those with post-high school
      education (4926 basepairs; B=125, SE=47.6, p=.009). A significant interaction of
      race and education (B=207.8, SE=98.7, p=.035) revealed more beneficial effects of
      post-high school education for blacks than for whites. Smokers had shorter LTL
      than non-smokers, but the association of education and LTL remained significant
      when smoking was covaried (B=119.7, SE=47.6, p=.012). While higher income was
      associated with longer LTL, the effect was not significant (p>.10). This study
      provides the first demonstration of an association between educational attainment
      and LTL in a US population where higher education appears to have a protective
      effect against telomere shortening, particularly in blacks.

PMID- 22981837
TI  - Bodies of risk: constructing motherhood in a Mexican public hospital.
AB  - This article addresses the connection between risk and motherhood at an urban
      obstetrics hospital in Mexico. It primarily aims to explore the ways that
      clinicians define risk as well as how they conflate risk with bad motherhood. It
      discusses how clinicians' perceptions of their patients' social lives shape their
      interactions and decisions about the women's health. The study was based on
      interviews and participant observation in June 2008 and June-July 2011 with 71
      obstetrical patients, 30 physicians, 9 nurses, and 12 midwives in the city of
      Puebla. Results show that birth itself was defined as a risky event, clinicians
      conflated social factors with biological factors in their management of risk, and
      the patients were a priori classified as bad mothers. This article proposes a
      reproductive habitus to explain the connection between health institutions,
      class, responsibility, blame, and clinical decision-making to analyze how risk is
      managed and blame enacted upon women's bodies.

PMID- 22981838
TI  - The impact of migratory separation from parents on the health of adolescents in
      the Philippines.
AB  - In the Philippines, as in several other low and middle-income countries in the
      world, it is usual for parents to leave the country to work abroad in order to
      improve the situation of their children who remain behind. However, stressful
      life events such as the separation from a parent are known to have a severe
      impact on physical and mental health of children. This study, conducted in 2008
      2009, explored health consequences of migratory separation for remaining-behind
      adolescent children, comparing them with those whose parents remained at home.
      Participants were 205 high school students from the Philippines. It was found
      that adolescents with a parent abroad, particularly the mother, reported poorer
      physical health than those with both parents at home, while socioeconomic status
      did not have impact. The parent-abroad adolescents reported a high level of
      missing their parent(s) and felt emotionally lonelier than the parent-at-home
      group. Emotional loneliness and stress due to parental absence were associated
      with poorer health. Avoidant coping appeared to moderate the parental absence
      health relationship. Paradoxically, it seems that, although many parents work
      abroad to improve the lot of their children, the latter suffer emotional stress
      and physical health detriments. While Lazarus and Folkman's (1984) cognitive
      stress model is generally applicable for migratory separation, cultural aspects
      need attention, both in theoretical implementation and interpretation.
      Limitations and implications are further discussed.

PMID- 22981839
TI  - Housing instability and health: findings from the Michigan Recession and Recovery
      Study.
AB  - The recession of the late 2000s has increased interest in the consequences of
      housing instability. Previous research has shown poorer health among those
      experiencing housing instability, but extant studies generally have focused on
      selected populations (e.g., homeowners or renters) or studied only one type of
      housing instability (e.g. homelessness). Using new data from the Michigan
      Recession and Recovery Study, a population-based sample of working-aged adults
      from Southeastern Michigan, U.S.A., in late 2009-early 2010, we found that about
      one-third of respondents recently experienced some type of housing instability.
      Many, but not all, types of instability were associated with health. Even after
      adjustment for sociodemographic characteristics and earlier health, individuals
      who had moved for cost reasons in the past three years were more likely than
      those with no housing instability to report a recent anxiety attack, while those
      who experienced homelessness in the past year had a higher likelihood of
      reporting fair/poor self-rated health and of meeting criteria for major or minor
      depression. Renters behind on rental payments were more likely to meet criteria
      for depression, while mortgage-holders behind on their mortgage or in foreclosure
      had a higher likelihood of reporting fair/poor self-rated health or a recent
      anxiety attack. Among respondents who had ever owned a home, those who completed
      a foreclosure recently were more likely to report major or minor depression or an
      anxiety attack. However, frequent moves were not associated with poorer health,
      and doubling up and eviction were not associated with poorer health after
      adjustment for characteristics that sort people into different housing
      instability experiences. Our findings suggest the importance of considering
      multiple types of housing instability and using appropriate risk groups and
      comparison categories.

PMID- 22981840
TI  - Embedded gender and social changes underpinning inequalities in health: an
      ethnographic insight into a local Spanish context.
AB  - Despite growing interest in the social determinants of health and contributions
      from studies focussing on the analysis of explanations to enhance our
      understanding of the interactions between gender identities, embodied experiences
      and structural inequalities between men and women, few research papers have
      devoted attention to this perspective in the Spanish context. This study is an
      empirical exploration of lay knowledge, for an enhanced understanding of health
      inequalities in this context, from an ethnographic standpoint based on a
      phenomenological approach. Specifically, our aim is to study the lay perceptions
      of men and women regarding their gender identity and living conditions as health
      determinants within different "contexts" of their everyday lives, namely: the
      personal context; the home context; and the neighbourhood context. Fifty eight in
      depth interviews and three focus groups were held between January 2005 and
      January 2007, and analysed using a hermeneutic method. Our findings show how
      disease-coping strategies or the perceived loss of social cohesion are linked to
      the gender system. They also point to how the dynamics of social change have
      developed around a strong division between the productive and reproductive
      arenas. Approaching these issues from different "contexts" provides insights into
      the explanations for the gendered patterning of mortality and morbidity, as well
      as furthering our understanding of the basis for social embodiment of gender
      differences and health inequalities in the context studied. In the discussion of
      our findings, we place emphasis on the implications that informal caring has for
      these processes and also take into account contributions of the "lay approach" to
      study and understand social determinants and health inequalities.

PMID- 22981841
TI  - MEG studies of sensorimotor rhythms: a review.
AB  - The human sensorimotor cortex demonstrates a variety of oscillatory activity that
      is strongly modulated by movement and somatosensory input. Studies using scalp
      EEG and intracranial electrical recordings have provided much of our current
      knowledge regarding the frequency and temporal specificity of these sensorimotor
      rhythms and their relationship to various movement parameters, however with
      limitations in identifying the underlying neural sources, and the variety of
      motor behaviors that can be studied, respectively. Magnetoencephalography (MEG)
      recordings, combined with spatial filtering source reconstruction methods,
      provide an ideal non-invasive method for the localization of sensorimotor rhythms
      and for describing their precise time course during a variety of motor tasks.
      This review describes the application of MEG to the study of oscillatory activity
      in the human sensorimotor cortex, including advances in localization techniques
      and recent contributions of MEG to our understanding of the functional role of
      these oscillations in both adult and developmental populations.

PMID- 22981842
TI  - The myth of the 'unaffected' side after unilateral stroke: is reorganisation of
      the non-infarcted corticospinal system to re-establish balance the price for
      recovery?
AB  - BACKGROUND: Bilateral changes in the hemispheric reorganisation have been
      observed chronically after unilateral stroke. Our hypotheses were that activity
      dependent competition between the lesioned and non-lesioned corticospinal systems
      would result in persisting asymmetry and be associated with poor recovery.
      METHODS: Eleven subjects (medium 6.5 years after stroke) were compared to 9 age
      matched controls. The power spectral density (PSD) of the sensorimotor
      electroencephalogram (SM1-EEG) and electromyogram (EMG) and corticomuscular
      coherence (CMC) were studied during rest and isometric contraction of right or
      left opponens pollicis (OP). Global recovery was assessed using NIH score.
      FINDINGS: There was bilateral loss of beta frequency activity in the SM1-EEGs and
      OP-EMGs in strokes compared to controls. There was no difference between strokes
      and controls in symmetry indices estimated between the two corticospinal systems
      for SM1-EEG, OP-EMG and CMC. Performance correlated with preservation of beta
      frequency power in OP-EMG in both hands. Symmetry indices for the SM1-EEG, OP-EMG
      and CMC correlated with recovery. INTERPRETATION: Significant changes occurred at
      both cortical and spinomuscular levels after stroke but to the same degree and in
      the same direction in both the lesioned and non-lesioned corticospinal systems.
      Global recovery correlated with the degree of symmetry between corticospinal
      systems at all three levels - cortical and spinomuscular levels and their
      connectivity (CMC), but not with the absolute degree of abnormality. Re
      establishing balance between the corticospinal systems may be important for
      overall motor function, even if it is achieved at the expense of the non-lesioned
      system.

PMID- 22981843
TI  - Evidence of community structure in biomedical research grant collaborations.
AB  - Recent studies have clearly demonstrated a shift towards collaborative research
      and team science approaches across a spectrum of disciplines. Such collaborative
      efforts have also been acknowledged and nurtured by popular extramurally funded
      programs including the Clinical Translational Science Award (CTSA) conferred by
      the National Institutes of Health. Since its inception, the number of CTSA
      awardees has steadily increased to 60 institutes across 30 states. One of the
      objectives of CTSA is to accelerate translation of research from bench to bedside
      to community and train a new genre of researchers under the translational
      research umbrella. Feasibility of such a translation implicitly demands multi
      disciplinary collaboration and mentoring. Networks have proven to be convenient
      abstractions for studying research collaborations. The present study is a part of
      the CTSA baseline study and investigates existence of possible community
      structure in Biomedical Research Grant Collaboration (BRGC) networks across data
      sets retrieved from the internally developed grants management system, the
      Automated Research Information Administrator (ARIA) at the University of Arkansas
      for Medical Sciences (UAMS). Fastgreedy and link-community community-structure
      detection algorithms were used to investigate the presence of non-overlapping and
      overlapping community-structure and their variation across years 2006 and 2009. A
      surrogate testing approach in conjunction with appropriate discriminant
      statistics, namely: the modularity index and the maximum partition density is
      proposed to investigate whether the community-structure of the BRGC networks were
      different from those generated by certain types of random graphs. Non-overlapping
      as well as overlapping community-structure detection algorithms indicated the
      presence of community-structure in the BRGC network. Subsequent, surrogate
      testing revealed that random graph models considered in the present study may not
      necessarily be appropriate generative mechanisms of the community-structure in
      the BRGC networks. The discrepancy in the community-structure between the BRGC
      networks and the random graph surrogates was especially pronounced at 2009 as
      opposed to 2006 indicating a possible shift towards team-science and formation of
      non-trivial modular patterns with time. The results also clearly demonstrate
      presence of inter-departmental and multi-disciplinary collaborations in BRGC
      networks. While the results are presented on BRGC networks as a part of the CTSA
      baseline study at UAMS, the proposed methodologies are as such generic with
      potential to be extended across other CTSA organizations. Understanding the
      presence of community-structure can supplement more traditional network analysis
      as they're useful in identifying research teams and their inter-connections as
      opposed to the role of individual nodes in the network. Such an understanding can
      be a critical step prior to devising meaningful interventions for promoting team
      science, multi-disciplinary collaborations, cross-fertilization of ideas across
      research teams and identifying suitable mentors. Understanding the temporal
      evolution of these communities may also be useful in CTSA evaluation.

PMID- 22981844
TI  - Mechanical stress meets autophagy: potential implications for physiology and
      pathology.
AB  - Changes in the mechanical environment are a universal challenge for cells, and
      mechanical cues regulate tissue structure and cell physiology throughout life.
      Autophagy is an important degradative pathway, fulfilling a wide range of roles
      in survival, homeostasis and adaptation. The two are connected, and in vitro,
      autophagy is rapidly induced in cells exposed to mechanical compression. In vivo,
      autophagy is also induced in several medically relevant circumstances that are
      also under mechanical stress such as bone and muscle homeostasis and tissue
      injury. The induction of autophagy has wide-ranging effects on cells. In this
      article, I propose that the autophagic response to mechanical stress is an
      important factor in a wide range of both physiological and pathological settings.

PMID- 22981846
TI  - Proteomic analysis of boar spermatozoa and quantity changes of superoxide
      dismutase 1, glutathione peroxidase, and peroxiredoxin 5 during epididymal
      maturation.
AB  - Mammalian spermatozoa and their various proteins undergo various modifications
      during maturation in the epididymis. To characterize proteins that change in
      quantity during this maturational process, boar spermatozoa were collected from
      various regions of the epididymis, and extracts were analyzed by two-dimensional
      gel electrophoresis (2-DE). A number of proteins were identified as changing in
      quantity, and MALDI-MS analysis revealed that superoxide dismutase 1 (SOD1) from
      the acrosomal proteins of spermatozoa, and glutathione peroxidase (GPX) and
      peroxiredoxin 5 from the membranous fraction increased during the epididymal
      transit of spermatozoa. These proteins are antioxidants that remove reactive
      oxygen species (ROS); they are presumed to protect spermatozoa during epididymal
      transit and storage. Western blot analysis of SOD1, GPX and peroxiredoxin 5
      showed that these protein levels increased as the spermatozoa traveled from the
      caput to the cauda epididymis. Activity analysis showed that total SOD activity
      also increased. Therefore, we conclude that several antioxidant proteins increase
      during the transit of boar spermatozoa through the epididymis, ultimately
      contributing to the maturation and/or survival of sperm.

PMID- 22981847
TI  - Levels of organochlorine contaminants in organic and conventional cheeses and
      their impact on the health of consumers: an independent study in the Canary
      Islands (Spain).
AB  - In the present work we have evaluated the levels of polychlorinated biphenyls
      (PCBs) and organochlorine pesticides (OCPs) in 61 commercially available brands
      of cheese (54 conventional and 7 organic) to estimate their relevance as a source
      of organochlorines. Our results showed that hexachlorobenzene, alpha-HCH,
      dieldrin, p,p'-DDE, and PCBs 153 and 180 were present in most of the samples
      independent of the cheese type. The concentration of OCPs was low for both types
      of cheese, although organic had lower concentrations than conventional. The
      estimated daily intake (EDI) of OCPs was lower than the tolerable daily intake
      (TDI). The levels of PCBs in cheese were also low; however, there were higher
      levels of PCBs in organic than in conventional brands. Levels of dioxin- like
      PCBs (DL-PCBs) in both types of cheese reached concentrations in the 75th
      percentile higher than 3 pg WHO-TEQ/g fat, and above 100% of the levels
      established by the EU. People consuming the most contaminated brands could have
      an EDI well above the recommended TDI (2 pg WHO-TEQ/kg bw/day). These results are
      of concern as the adverse health effects exerted by dioxin-like compounds are
      well known.

PMID- 22981848
TI  - Revaccination with Fendrix(r) or HBVaxPro(r) results in better response rates
      than does revaccination with three doses of Engerix-B(r) in previous non
      responders.
AB  - Because non-response (<10 IU/l anti-HBs) after revaccination for hepatitis B
      occurs frequently (50%), this study aimed to provide evidence for a more
      effective revaccination regimen by comparing four different revaccinations: (1)
      three revaccinations with Engerix-B((r)) (n=201); (2) one revaccination with
      Engerix-B((r)) (n=37); (3) one revaccination with HBVaxPro-40((r)) (n=108); (4)
      one revaccination with Fendrix((r)) (n=39). The level of anti-HBs antibodies was
      determined with the AXSYM-MEIA system (Abbott, Chicago, USA). Using linear and
      logistic regression, the efficacy (antibody response) after the four
      revaccinations was compared. Analyses were corrected for age, sex, primary titre
      and time lag between last revaccination and the titre measurement. The height of
      the primary titre independently predicted antibody response. Compared to the
      revaccination scheme using three Engerix-B((r)) doses, revaccination with a
      single dose of HBVaxPro-40((r)) or Fendrix((r)) performed significantly better.
      The use of these highly potent vaccines should be considered when revaccinating
      hepatitis B vaccine non-responders.

PMID- 22981845
TI  - The outdoor air pollution and brain health workshop.
AB  - Accumulating evidence suggests that outdoor air pollution may have a significant
      impact on central nervous system (CNS) health and disease. To address this issue,
      the National Institute of Environmental Health Sciences/National Institute of
      Health convened a panel of research scientists that was assigned the task of
      identifying research gaps and priority goals essential for advancing this growing
      field and addressing an emerging human health concern. Here, we review recent
      findings that have established the effects of inhaled air pollutants in the
      brain, explore the potential mechanisms driving these phenomena, and discuss the
      recommended research priorities/approaches that were identified by the panel.

PMID- 22981849
TI  - Maternal antibody parameters of cattle and calves receiving EG95 vaccine to
      protect against Echinococcus granulosus.
AB  - Cattle may act as hosts for the transmission of the cestode parasite Echinococcus
      granulosus and play a role in transmission of the parasite leading to human
      cystic echinococcosis (CE). The recombinant EG95 vaccine has been shown to be
      able to protect cattle and other intermediate host species against CE. Ideally
      the immunisation of bovines against E. granulosus, using EG95 vaccine, should
      occur early in life so as to provide maximum protection against the establishment
      of hydatid cysts. Maternally derived antibody from vaccinated cows may provide
      some protection for the neonate, but may also interfere with the active response
      to vaccination. Experiments were undertaken to determine the optimal regime for
      protection of young cattle against CE. One group of pregnant cattle received 2
      vaccinations of EG95 antigen+Quil A adjuvant two months and one month prior to
      calving. The control group of pregnant cattle were not vaccinated. Calves were
      either challenged with E. granulosus eggs at 4, 9, 13 or 17 weeks post-birth or
      were given their first vaccination at 8, 12 or 16 weeks post-birth. Sera obtained
      at regular intervals were tested by ELISA to assess the immunological response.
      All calves were experimentally challenged with E. granulosus eggs and subsequent
      necropsy confirmed the levels of protection. Maternal antibody was shown to
      protect calves to some extent for at least 17 weeks. Calves from vaccinated cows
      responded well serologically if the first vaccination was given at 8 or 12 weeks,
      but full protection against a challenge infection was achieved only if the first
      vaccination was delayed until 16 weeks after birth. Calves from non-vaccinated
      cattle also were not fully protected if the first vaccination was at 8 or 12
      weeks, but were fully protected if the first vaccination was given when they were
      16 weeks old. This suggests that immunological maturity is not acquired in calves
      until 4 or 5 months of age. No safety problems were observed following two
      vaccinations of 40 pregnant cows or 30 suckling calves.

PMID- 22981850
TI  - Report of the 5th meeting on influenza vaccines that induce broad spectrum and
      long-lasting immune responses, World Health Organization, Geneva, 16-17 November
      2011.
AB  - On 16-17 November 2011, the Initiative for Vaccine Research of the World Health
      Organization convened jointly with the Wellcome Trust the fifth meeting on
      'Influenza vaccines that induce broad spectrum and long-lasting immune
      responses'. The goals of the meeting were to examine new influenza vaccine
      research developments related to increased duration and breadth of protection,
      including immune responses against novel strains that may present zoonotic and
      pandemic threats; improved delivery and administration; and safety issues related
      to novel vaccine approaches. A number of investigational vaccines based on unique
      antigens, adjuvants, and/or modes of delivery were presented. The challenges for
      feasible regulatory pathways to approval of such vaccines were discussed.

PMID- 22981851
TI  - Topical tacrolimus treatment does not facilitate photocarcinogenesis in cancer
      prone mice.

PMID- 22981853
TI  - [Metabolic syndrome in workers in a university hospital].
AB  - INTRODUCTION: Metabolic syndrome (MS) is a major health problem, and has economic
      effects on enterprises. The workplace is thus an important environment for
      primary prevention of risk factors for cardiovascular disease. OBJECTIVE: To
      determine the prevalence of MS and variables related to its development in
      hospital workers. METHODS: We performed a cross-sectional study of 740 workers in
      a large university hospital. Socioeconomic variables, anthropometric and blood
      pressure measurements, and laboratory exams were analyzed. MS was defined
      according to the criteria of the International Diabetes Federation. RESULTS: Of
      the 740 workers, 72.4% were female and mean age was 34.9+/-9.5 years; 27.8%
      worked the morning shift, 20.3% the afternoon shift, 34.1% office hours, and
      17.8% the night shift. As to educational level, 86.6% had finished high school or
      college. Waist circumference was high in 55.4%. Overall MS prevalence was 12.8%,
      16.2% in males and 11.6% in females. Logistic regression analysis showed an
      independent association between MS and the following variables: elementary
      education, period of employment >10 years, office hours shift, and age group.
      CONCLUSION: A diagnosis of MS was affected by age, educational level, work shift,
      and prolonged period of employment. Hospital workers do not differ from other
      populations and also need stimuli to make preventive changes to their behavior to
      modify cardiovascular risk factors.

PMID- 22981852
TI  - Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal
      pneumonia through reduced cellular senescence.
AB  - Rapamycin, a potent immunomodulatory drug, has shown promise in the amelioration
      of numerous age-associated diseases including cancer, Alzheimer's disease and
      cardiac hypertrophy. Yet the elderly, the population most likely to receive
      therapeutic rapamycin, are already at increased risk for infectious disease; thus
      concern exists that rapamycin may exacerbate age-associated immune dysfunctions
      and worsen infection outcomes. Herein, we examined the impact of enteric
      delivered rapamycin monotherapy (eRapa) on the susceptibility of aged (22
      24month) C57BL/6 mice to Streptococcus pneumoniae, the leading bacterial cause of
      community-acquired pneumonia. Following challenge with S. pneumoniae,
      administration of eRapa conferred modest protection against mortality. Reduced
      mortality was the result of diminished lung damage rather than reduced bacterial
      burden. eRapa had no effect on basal levels of Interleukin (IL)-1alpha, IL-6, IL
      10, IL-12p70, KC, Interferon-gamma, Tumor necrosis factor alpha and Monocyte
      chemotactic protein-1 in whole lung homogenates or during pneumococcal pneumonia.
      Previously we have demonstrated that cellular senescence enhances permissiveness
      for bacterial pneumonia through increased expression of the bacterial ligands
      Laminin receptor (LR), Platelet-activating factor receptor (PAFr) and Cytokeratin
      10 (K10). These proteins are co-opted by S. pneumoniae and other respiratory
      tract pathogens for host cell attachment during lung infection. UM-HET3 mice on
      eRapa had reduced lung cellular senescence as determined by levels of the
      senescence markers p21 and pRB, but not mH2A.1. Mice on eRapa also had marked
      reductions in PAFr, LR, and K10. We conclude that eRapa protected aged mice
      against pneumonia through reduced lung cellular senescence, which in turn,
      lowered bacterial ligand expression.

PMID- 22981854
TI  - AdaptiveIterative Dose Reduction in coronary CT angiography using 320-row CT:
      assessment of radiation dose reduction and image quality.
AB  - BACKGROUND: Several methods have been developed to reduce the radiation dose in
      coronary computed tomography angiography (CTA). OBJECTIVE: The objective of our
      study was to evaluate the effects of Adaptive Iterative Dose Reduction (AIDR) on
      objective and subjective image quality as well as the radiation dose, compared
      with conventional filtered back projection (FBP), in coronary CTA. METHODS: We
      retrospectively reviewed 100 consecutive patients who underwent coronary CTA. In
      the first 50 patients, a higher tube current was used, and images were
      reconstructed with FBP. In the last 50 patients, a lower tube current was used,
      and images were reconstructed with AIDR. Subjective and objective image quality
      (noise, signal-to-noise ratio, contrast-to-noise ratio) were assessed. RESULTS:
      The median radiation dose of the AIDR group was 22% lower than that of the FBP
      group (4.2 vs 5.4 mSv; P = 0.0001). No significant difference was found in
      subjective image quality, noise, signal-to-noise ratio, or contrast-to-noise
      ratio between the 2 groups. CONCLUSION: AIDR reduced the tube current which
      resulted in reduction of radiation dose in coronary CTA while maintaining
      subjective and objective image quality compared with coronary CTA reconstructed
      with FBP.

PMID- 22981855
TI  - Gerbode-type left ventricular outflow tract to right atrial fistula complicating
      prosthetic aortic valve replacement identified by cardiac computed tomographic
      angiography.
AB  - Acquired left ventricular-right atrial communication (Gerbode-type defect) is a
      rare complication of infective endocarditis. Although transesophageal
      echocardiography remains the technique of choice for the evaluation of
      complications of endocarditis this case highlights the usefulness of cardiac
      computed tomography in this scenario, particularly in cases where assessment of
      coronary anatomy is required before surgery.

PMID- 22981857
TI  - Where we have been and the way forward.

PMID- 22981856
TI  - Risk stratification of non-contrast CT beyond the coronary calcium scan.
AB  - Coronary artery calcification (CAC) is a well-known marker for coronary artery
      disease and has important prognostic implications. CAC is able to provide
      clinicians with a reliable source of information related to cardiovascular
      atherosclerosis, which carries incremental information beyond Framingham risk.
      However, non-contrast scans of the heart provide additional information beyond
      the Agatston score. These studies are also able to measure various sources of
      fat, including intrathoracic (eg, pericardial or epicardial) and hepatic, both of
      which are thought to be metabolically active and linked to increased incidence of
      subclinical atherosclerosis as well as increased prevalence of type 2  diabetes.
      Testing for CAC is also useful in identifying extracoronary sources of
      calcification. Specifically, aortic valve calcification, mitral annular
      calcification, and thoracic aortic calcium (TAC) provide additional risk
      stratification information for cardiovascular events. Finally, scanning for CAC
      is able to evaluate myocardial scaring due to myocardial infarcts, which may also
      add incremental prognostic information. To ensure the benefits outweigh the risks
      of a scanning for CAC for an appropriately selected asymptomatic patient, the
      full utility of the scan should be realized. This review describes the current
      state of the art interpretation of non-contrast cardiac CT, which clinically
      should go well beyond coronary artery Agatston scoring alone.

PMID- 22981858
TI  - Single injection, inspiratory/expiratory high-pitch dual-source CT angiography
      for median arcuate ligament syndrome: novel technique for a classic diagnosis.
AB  - This article discusses a novel technique for dynamic imaging of median arcuate
      ligament syndrome utilizing low dose CT technology and a single contrast
      injection.

PMID- 22981859
TI  - Left ventricular noncompaction: a proposal of new diagnostic criteria by
      multidetector computed tomography.
AB  - BACKGROUND: Left ventricular noncompaction (LVNC) is a cardiomyopathy
      characterized by a noncompacted myocardial layer in the left ventricle, primarily
      diagnosed by echocardiographic and magnetic resonance criteria. Multidetector
      computed tomography (MDCT) is an imaging method that has been increasingly used
      in cardiac evaluation. However, tomographic criteria to diagnose LVNC have not
      been determined. OBJECTIVES: We assessed the structural characteristics of LVNC
      with MDCT and proposed tomographic criteria that may differentiate LVNC from
      healthy subjects and patients with other cardiomyopathies that might be
      associated with increased myocardial trabeculation. METHODS: Between March 2007
      and June 2009 we studied 10 consecutive patients with LVNC diagnosed by
      echocardiogram and/or magnetic resonance imaging who underwent electrocardiogram
      gated coronary CT angiography. We evaluated the ratio of noncompacted to
      compacted myocardium (NC/C ratio) in end diastole in each of the 17 segments
      established by the American Heart Association (excluding the apex). The results
      were compared with 9 healthy subjects, 14 patients with hypertrophic
      cardiomyopathy, and 17 patients with dilated cardiomyopathy to determine the
      cutoff that would distinguish patients with LVNC. RESULTS: When considering
      involvement of more than 1 segment, the NC/C ratio of 2.2 distinguished
      pathologic noncompaction, with sensitivity and specificity of 100% and 95%,
      respectively. In addition, the involvement of >=2 segments allows the distinction
      of all patients with LVNC from other cardiomyopathies and from healthy subjects.
      CONCLUSIONS: LVNC can be accurately diagnosed with MDCT when using a cutoff NC/C
      ratio of 2.2 at end diastole involving >=2 segments.

PMID- 22981860
TI  - Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of
      viability and stress resistance.
AB  - Cells constantly adjust their metabolism in response to environmental conditions,
      yet major mechanisms underlying survival remain poorly understood. We discover a
      posttranscriptional mechanism that integrates starvation response with GTP
      homeostasis to allow survival, enacted by the nucleotide (p)ppGpp, a key player
      in bacterial stress response and persistence. We reveal that (p)ppGpp activates
      global metabolic changes upon starvation, allowing survival by regulating GTP.
      Combining metabolomics with biochemical demonstrations, we find that (p)ppGpp
      directly inhibits the activities of multiple GTP biosynthesis enzymes. This
      inhibition results in robust and rapid GTP regulation in Bacillus subtilis, which
      we demonstrate is essential to maintaining GTP levels within a range that
      supports viability even in the absence of starvation. Correspondingly, without
      (p)ppGpp, gross GTP dysregulation occurs, revealing a vital housekeeping function
      of (p)ppGpp; in fact, loss of (p)ppGpp results in death from rising GTP, a severe
      and previously unknown consequence of GTP dysfunction.

PMID- 22981862
TI  - Circadian Dbp transcription relies on highly dynamic BMAL1-CLOCK interaction with
      E boxes and requires the proteasome.
AB  - The transcription factors BMAL1 and CLOCK drive the circadian transcription of
      clock and clock-controlled genes, such as Dbp. To investigate the kinetics of
      BMAL1 binding to target genes in real time, we generated a cell line harboring
      tandem arrays of Dbp repeats and monitored the binding of a fluorescent BMAL1
      fusion protein to these arrays by time-lapse microscopy. BMAL1 occupancy at the
      Dbp locus was highly circadian and strictly dependent on CLOCK. Moreover, BMAL1
      CLOCK associations with Dbp were extremely unstable and displayed stochastic,
      proteasome-dependent fluctuations. Proteasome inhibition prolonged the residence
      time of BMAL1-CLOCK but resulted in an immediate attenuation of Dbp
      transcription. In cells harboring a single Dbp-luciferase reporter gene copy,
      this silencing was shown to be caused by a decrease in both the frequencies and
      sizes of transcriptional bursts. Thus, BMAL1 and CLOCK may act as Kamikaze
      activators, in that they are rapidly degraded once bound to Dbp chromatin.

PMID- 22981861
TI  - Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion
      and noncanonical scurvy in mice.
AB  - Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to
      oxidatively fold secreted proteins. We found that combined loss-of-function
      mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta, and PRDX4
      compromised the extracellular matrix in mice and interfered with the
      intracellular maturation of procollagen. These severe abnormalities were
      associated with an unexpectedly modest delay in disulfide bond formation in
      secreted proteins but a profound, 5-fold lower procollagen 4-hydroxyproline
      content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue
      ascorbic acid content was lower in mutant mice, and ascorbic acid supplementation
      improved procollagen maturation and lowered sulfenic acid content in vivo. In
      vitro, the presence of a sulfenic acid donor accelerated the oxidative
      inactivation of ascorbate by an H(2)O(2)-generating system. Compromised ER
      disulfide relay thus exposes protein thiols to competing oxidation to sulfenic
      acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4
      hydroxylation, and a noncanonical form of scurvy.

PMID- 22981863
TI  - LAT-independent Erk activation via Bam32-PLC-gamma1-Pak1 complexes: GTPase
      independent Pak1 activation.
AB  - In T cells, the adaptor Bam32 is coupled to Erk activation downstream of the TCR
      by an unknown mechanism. We characterized in Jurkat cells and primary T
      lymphocytes a pathway dependent on Bam32-PLC-gamma1-Pak1 complexes, in which Pak1
      kinase activates Raf-1 and Mek-1, both upstream of Erk. In the Bam32-PLC-gamma1
      Pak1 complex, catalytically inactive PLC-gamma1 is used as a scaffold linking
      Bam32 to Pak1. PLC-gamma1(C-SH2) directly binds S141 of Bam32, preventing LAT
      mediated activation of Ras by PLC-gamma1. The Bam32-PLC-gamma1 interaction
      enhances the binding of the SH3 domain of the phospholipase with Pak1. The PLC
      gamma1(SH3)-Pak1 interaction activates Pak1 independently of the small GTPases
      Rac1/Cdc42, previously described as being the only activators of Pak1 in T cells.
      Direct binding of the SH3 domain of PLC-gamma1 to Pak1 dissociates inactive Pak1
      homodimers, a mechanism required for Pak1 activation. We have thus uncovered a
      LAT/Ras-independent, Bam32-nucleated pathway that activates Erk signaling in T
      cells.

PMID- 22981864
TI  - Genome-wide measurement of RNA folding energies.
AB  - RNA structural transitions are important in the function and regulation of RNAs.
      Here, we reveal a layer of transcriptome organization in the form of RNA folding
      energies. By probing yeast RNA structures at different temperatures, we obtained
      relative melting temperatures (Tm) for RNA structures in over 4000 transcripts.
      Specific signatures of RNA Tm demarcated the polarity of mRNA open reading frames
      and highlighted numerous candidate regulatory RNA motifs in 3' untranslated
      regions. RNA Tm distinguished noncoding versus coding RNAs and identified mRNAs
      with distinct cellular functions. We identified thousands of putative RNA
      thermometers, and their presence is predictive of the pattern of RNA decay in
      vivo during heat shock. The exosome complex recognizes unpaired bases during heat
      shock to degrade these RNAs, coupling intrinsic structural stabilities to gene
      regulation. Thus, genome-wide structural dynamics of RNA can parse functional
      elements of the transcriptome and reveal diverse biological insights.

PMID- 22981867
TI  - Biological variation of free light chains in serum.

PMID- 22981865
TI  - Tet2 facilitates the derepression of myeloid target genes during CEBPalpha
      induced transdifferentiation of pre-B cells.
AB  - The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic
      differentiation and the formation of myeloid malignancies when mutated. An ideal
      system to study the role of Tet2 in myelopoeisis is CEBPalpha-induced
      transdifferentiation of pre-B cells into macrophages. Here we found that
      CEBPalpha binds to upstream regions of Tet2 and that the gene becomes activated.
      Tet2 knockdowns impaired the upregulation of macrophage markers as well as
      phagocytic capacity, suggesting that the enzyme is required for both early and
      late stage myeloid differentiation. A slightly weaker effect was seen in primary
      cells with a Tet2 ablation. Expression arrays of transdifferentiating cells with
      Tet2 knockdowns permitted the identification of a small subset of myeloid genes
      whose upregulation was blunted. Activation of these target genes was accompanied
      by rapid increases of promoter hydroxy-methylation. Our observations indicate
      that Tet2 helps CEBPalpha rapidly derepress myeloid genes during the conversion
      of pre-B cells into macrophages.

PMID- 22981868
TI  - High expression of interleukin 10 might predict poor prognosis in early stage
      oral squamous cell carcinoma patients.
AB  - BACKGROUND: Interleukin 10 (IL10) plays an important role in immunosuppression
      and suppression of antitumor immunity. This study examined the IL10 expression of
      tumor cells and assessed its significance in patients with oral squamous cell
      carcinoma (OSCC). METHODS: Tumor tissues and adjacent normal tissues were
      obtained from 325 patients with OSCC and were arranged in a tissue microarray. We
      examined 325 surgical specimens for associations between IL10 expression in tumor
      cells and clinical parameters of oral cancer. RESULTS: High IL10 expression in
      OSCC patients was significantly associated with male gender (P<0.001), smoking
      (P=0.015), alcohol consumption (P=0.018), betel quid chewing (P=0.003), poor
      relapse free survival (P=0.012), and poor overall survival (P=0.001). Patients
      with high IL10 expression, and particularly early stage OSCC patients, had
      significantly worse overall survival as defined by the log-rank test (P=0.014 for
      all cases; P=0.004 for early stage patients). In early stage patients, high IL10
      expression in tumor cells was associated with poor prognosis (P=0.018) and a 1.99
      fold higher death risk, as determined by Cox regression. CONCLUSION: High IL10
      expression is significantly associated with aggressive clinical manifestations
      and might be an independent survival predictor, particularly in early stage OSCC
      patients.

PMID- 22981869
TI  - Lipid metabolism in microalgae distinguishes itself.
AB  - Microalgae are attracting renewed interest from both the scientific and public
      communities owing to their potential applications as sustainable feed stocks for
      the production of biofuels and high value compounds, and environmental
      remediation. Recent advances in molecular and biochemical analyses of microalgae
      point toward interesting differences in lipid metabolism between algal species
      and in comparison to plants. These differences range from distinct acyl groups
      present in algal lipids, to a possible more direct role of plastids in the
      assembly of TAGs with consequences for the overall subcellular organization of
      glycerolipid metabolism. Thus, studying lipid metabolism in microalgae points to
      new possible avenues of genetic engineering of lipid metabolism in this organism
      group, and may also inform studies of lipid metabolism in plants.

PMID- 22981870
TI  - Bioavailability of pollutants and chemotaxis.
AB  - The exposure of bacteria to pollutants induces frequently chemoattraction or
      chemorepellent reactions. Recent research suggests that the capacity to degrade a
      toxic compound has co-evolved in some bacteria with the capacity to
      chemotactically react to it. There is an increasing amount of data which show
      that chemoattraction to biodegradable pollutants increases their bioavailability
      which translates into an enhancement of the biodegradation rate. Pollutant
      chemoreceptors so far identified are encoded on degradation or resistance
      plasmids. Genetic engineering of bacteria, such as the transfer of chemoreceptor
      genes, offers thus the possibility to optimize biodegradation processes.

PMID- 22981871
TI  - The Zebrafish Anatomy Portal: a novel integrated resource to facilitate zebrafish
      research.
AB  - Zebrafish is a common model organism in research and yet, despite its widespread
      use, anatomical resources for this species are incomplete or lacking in
      functionality. There remains a need for a single reference resource that
      integrates user-friendly tools to facilitate the identification of structures,
      display of reference images, provides data on gene expression, links to relevant
      literature, and covers the complete range of zebrafish developmental stages. To
      fulfill this need, we have designed the Zebrafish Anatomy Portal (www.zfap.org),
      containing annotated three-dimensional images of zebrafish at stages throughout
      development and adulthood, acquired by optical projection tomography. ZFAP
      combines functionalities to allow scanning through 3D data sets, searching of
      images by anatomical terms, predictions of gene expression from literature
      analysis, and facilitation of the identification of relevant literature through
      assisted searching of the NCBI PubMed resource. ZFAP provides a highly functional
      anatomical resource that will aid future education and research in the zebrafish
      model system.

PMID- 22981872
TI  - Letter regarding "Keloid formation after circumcision and its treatment".

PMID- 22981873
TI  - Potentiation of amyloid-beta peptide neurotoxicity in human dental-pulp neuron
      like cells by the membrane lipid peroxidation product 4-hydroxynonenal.
AB  - Lipid peroxidation is generally considered as primarily implicated in the
      pathogenesis of Alzheimer's disease (AD); one of its more reactive end products,
      4-hydroxynonenal (HNE), has been shown to cause neuron dysfunction and
      degeneration. HNE production in the brain is stimulated by the amyloid-beta
      peptide (Abeta), whose excessive accumulation in specific brain areas is a
      hallmark of AD. Conversely, Abeta production is up-regulated by this
      multifunctional aldehyde. Findings reported here point to the ability of HNE and
      Abeta to interact, with consequent potentiation of Abeta's cytotoxicity as
      determined in vitro using neuron-like cells derived from human dental-pulp
      progenitor cells. Preincubation of cells with the aldehyde markedly up-regulated
      Abeta uptake and intracellular accumulation, by overexpressing two of the three
      components of the plasma membrane multireceptor complex CD36/CD47/beta1-integrin:
      experimental and clinical data indicate that intraneuronal accumulation of Abeta
      is an early event possibly playing a primary role in AD pathogenesis. That HNE
      mediated overexpression of CD36 and beta1-integrin, which plays a key role in
      HNE's potentiating Abeta neurotoxicity, in terms of necrosis, was confirmed when
      this effect was prevented by specific antibodies against the two receptors.

PMID- 22981874
TI  - The incidence of medulloblastomas and primitive neurectodermal tumours in adults
      and children.
AB  - Medulloblastomas (MB) and primitive neurectodermal tumours (PNET) are known to
      affect children more than adults. To estimate the magnitude of the differences
      between the incidence of adults and children, the incidence rates, ratios and
      time trends of MB and PNET in children and adults are measured using data from
      the Surveillance, Epidemiology and End-Results (SEER) database. Between 1973 and
      2007 in the SEER 9 registries, 1372 people were diagnosed with a MB and 530 with
      a PNET. The overall incidence rate of MB and PNET is approximately 1.5 and 0.62
      per million population in the USA. Children (1-9 years of age) with MB had an
      incidence rate of 6.0, compared to 0.6 in adults, and therefore children are 10
      times more likely to be affected by an MB than adults. Children are 4.6 times as
      likely to be afflicted by a PNET than adults. The difference in incidence rates
      based on sex existed only in children. Our study confirmed that the incidence
      rates of MB has not changed over time.

PMID- 22981878
TI  - Implicit and explicit categorization: a tale of four species.
AB  - Categorization is essential for survival, and it is a widely studied cognitive
      adaptation in humans and animals. An influential neuroscience perspective
      differentiates in humans an explicit, rule-based categorization system from an
      implicit system that slowly associates response outputs to different regions of
      perceptual space. This perspective is being extended to study categorization in
      other vertebrate species, using category tasks that have a one-dimensional, rule
      based solution or a two-dimensional, information-integration solution. Humans,
      macaques, and capuchin monkeys strongly dimensionalize perceptual stimuli and
      learn rule-based tasks more quickly. In sharp contrast, pigeons learn these two
      tasks equally quickly. Pigeons represent a cognitive system in which the
      commitment to dimensional analysis and category rules was not strongly made.
      Their results may reveal the character of the ancestral vertebrate categorization
      system from which that of primates emerged. The primate results establish
      continuity with human cognition, suggesting that nonhuman primates share aspects
      of humans' capacity for explicit cognition. The emergence of dimensional analysis
      and rule learning could have been an important step in primates' cognitive
      evolution.

PMID- 22981879
TI  - Theriogenology. Foreword.

PMID- 22981881
TI  - Increased dimerization of alpha-synuclein in erythrocytes in Gaucher disease and
      aging.
AB  - Gaucher disease (GD) patients and carriers of glucocerebrosidase mutations are at
      an increased risk for Parkinson's disease (PD). The presynaptic protein alpha
      synuclein (AS) is linked to PD. In the current work we examined biochemical
      properties of AS in GD patients. We generated membrane-enriched lysates from
      erythrocytes of 27 patients with GD and 32 age- and sex-matched controls and
      performed Western immunoblotting with antibodies against AS. Levels of monomeric
      AS did not differ between GD patients and controls and did not change as a
      function of age. However, the ratio of dimeric to monomeric AS was significantly
      increased in GD patients, and showed a significant positive correlation with age.
      Therefore, two major risk factors for PD, aging and GD status, are associated
      with an increased AS dimer to monomer ratio in erythrocytes. This ratio needs to
      be validated in further studies as a potential biomarker for PD risk.

PMID- 22981882
TI  - Temporal auditory processing at 17 months of age is associated with preliterate
      language comprehension and later word reading fluency: an ERP study.
AB  - Dyslexia is heritable and associated with auditory processing deficits. We
      investigate whether temporal auditory processing is compromised in young children
      at-risk for dyslexia and whether it is associated with later language and reading
      skills. We recorded EEG from 17 months-old children with or without familial risk
      for dyslexia to investigate whether their auditory system was able to detect a
      temporal change in a tone pattern. The children were followed longitudinally and
      performed an intelligence- and language development test at ages 4 and 4.5 years.
      Literacy related skills were measured at the beginning of second grade, and word-
      and pseudo-word reading fluency were measured at the end of second grade. The EEG
      responses showed that control children could detect the temporal change as
      indicated by a mismatch response (MMR). The MMR was not observed in at-risk
      children. Furthermore, the fronto-central MMR amplitude correlated with
      preliterate language comprehension and with later word reading fluency, but not
      with phonological awareness. We conclude that temporal auditory processing
      differentiates young children at risk for dyslexia from controls and is a
      precursor of preliterate language comprehension and reading fluency.

PMID- 22981880
TI  - Genome resource banking of biomedically important laboratory animals.
AB  - Genome resource banking is the systematic collection, storage, and redistribution
      of biomaterials in an organized, logistical, and secure manner. Genome cryobanks
      usually contain biomaterials and associated genomic information essential for
      progression of biomedicine, human health, and research. In that regard,
      appropriate genome cryobanks could provide essential biomaterials for both
      current and future research projects in the form of various cell types and
      tissues, including sperm, oocytes, embryos, embryonic or adult stem cells,
      induced pluripotent stem cells, and gonadal tissues. In addition to cryobanked
      germplasm, cryobanking of DNA, serum, blood products, and tissues from
      scientifically, economically, and ecologically important species has become a
      common practice. For revitalization of the whole organism, cryopreserved
      germplasm in conjunction with assisted reproductive technologies, offer a
      powerful approach for research model management, as well as assisting in animal
      production for agriculture, conservation, and human reproductive medicine.
      Recently, many developed and developing countries have allocated substantial
      resources to establish genome resources banks which are responsible for
      safeguarding scientifically, economically, and ecologically important wild type,
      mutant, and transgenic plants, fish, and local livestock breeds, as well as
      wildlife species. This review is dedicated to the memory of Dr. John K. Critser,
      who has made profound contributions to the science of cryobiology and
      establishment of genome research and resources centers for mice, rats, and swine.
      Emphasis will be given to application of genome resource banks to species with
      substantial contributions to the advancement of biomedicine and human health.

PMID- 22981883
TI  - An ERP study on the understanding of the distinction between real and apparent
      emotions.
AB  - To ensure successful social interactions, we must appropriately understand the
      distinction between apparent and real emotions. Here, we used event-related
      potential (ERP) methodology to examine the neural correlates of adults' decoding
      of another's apparent and real emotions. Participants were asked to judge whether
      the protagonist's apparent emotion (facial expression) was consistent with the
      real emotion (inner experience). The "false happiness" and "real sadness" stimuli
      elicited smaller P2 amplitudes than "real happiness" and "false sadness".
      Similarly, compared to "real happiness" and "false sadness", "false happiness"
      and "real sadness" stimuli elicited more negative deflections on the N200 and
      N300 components. These results indicate that the human brain does not simply
      detect emotion by facial expressions, but is capable of evaluating the context
      and deducing that person's true state of mind.

PMID- 22981884
TI  - P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in
      mice.
AB  - Ectopic pain in other orofacial regions develops with local inflammation in
      separated orofacial structures. However, the basis for the spreading of pain to
      adjacent orofacial areas after local inflammation is still unknown. In the
      present study, we determined if the P2X(3) receptor (P2X(3)R) was associated with
      altered mechanical sensitivity of the whisker pad skin following complete
      Freund's adjuvant (CFA) injection into the lower lip. Mice with local
      inflammation induced by CFA injection into the lower lip demonstrated significant
      mechanical allodynia of whisker pad skin. The mechanical allodynia was reversed
      by P2X(3)R antagonist, A-317491 administration into whisker pad skin. The number
      of P2X(3)R and calcitonin gene-related peptide (CGRP) positive trigeminal
      ganglion (TG) neurons that innervates the whisker pad skin and lower lip was
      increased after CFA injection into the lower lip. CGRP protein expression in TG
      ipsilateral to CFA injection was also significantly greater than that of the
      saline-injected mice. The present findings suggest that induced CGRP by local
      inflammation in the lower lip increases P2X(3)R in TG neurons, the increased
      P2X(3)Rs are involved in the sensitization of primary afferent neurons in the
      whisker pad skin. This P2X(3)R overexpression may underlie ectopic mechanical
      allodynia in the whisker pad skin after CFA injection into the lower lip.

PMID- 22981885
TI  - Cutaneous silent period in hand muscles is lengthened by tramadol: Evidence for
      monoaminergic modulation?
AB  - The purpose of this study was to shed light on the neurochemical modulatory
      mechanisms of the noxious spinal inhibitory cutaneous silent period (CSP). We
      study the effects of 100mg of oral tramadol in 11 healthy volunteers. Tramadol
      has low affinity for opioid receptors and has the ability to inhibit serotonin
      and noradrenaline reuptake. We elicited CSPs in the first dorsal interosseus
      muscle and noxious withdrawal flexor reflexes (NWR) in the right biceps femoris
      muscle before, 30 min and each hour up to the 6th after tramadol. Subjective pain
      sensation was checked on an 11-point numerical scale. Tramadol increased duration
      of CSP, and reduced the NWR area under the curve maximally 2h after tramadol and
      paralleled the reduction of subjective pain perception. We suggest that the
      monoaminergic action of tramadol reinforces the activity of spinal inhibitory
      interneurons on alpha-motoneurons for the hand muscles.

PMID- 22981886
TI  - An evaluation of polymorphisms in casein kinase 1 delta and epsilon genes in
      major psychiatric disorders.
AB  - Disturbances of the circadian rhythm are involved in the pathophysiology of
      bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD).
      Specifically, because clock gene dysfunction is good candidate for enhancing the
      susceptibility to these psychiatric disorders, we selected two circadian rhythm
      related genes (CSNK1D and CSNK1E) and investigated genetic associations of the
      genes with these three disorders. None of the SNPs showed a significant
      association with MDD, but a SNP (rs2075984) in CSNK1E and SNP (rs6502097) in
      CSNK1D were associated with SCZ (P=0.0091, uncorrected) and BD (P=0.030,
      uncorrected), respectively. To confirm these findings, we analyzed an independent
      dataset (maximum N=3815) but found a lack of association (P=0.63 for rs2075984
      and P=0.61 for rs6502097). The final meta-analysis showed no association between
      these SNPs with SCZ (P=0.21) and BD (P=0.53). These results do not support that
      genetic variation in CSNK1D and CSNK1E is a susceptibility factor for major
      psychiatric disorders in the Japanese population.

PMID- 22981887
TI  - Putting culture in the curriculum: a European project.
AB  - The purpose of this paper is to describe the rationale for and the method of
      designing a framework for a European curriculum to promote intercultural
      competence in health care students. The background relating to the migration of
      people into and across Europe is cited as the factor driving the need for such a
      project. The project group emerged from the European organisation known as
      COHEHRE (Consortium of Higher Education Institutes in Health and Rehabilitation
      in Europe). Composed of a group of nurse educators from 5 European countries it
      charts the process which led them to create a curriculum framework. The completed
      work is available in the form of a CD-ROM. The paper describes the steps taken to
      reach the project outcomes over 4 years. The methods of dissemination of the
      project outcomes are included. The discussion considers the journey of the group
      towards the outcomes of the project and identifies the need to discover how
      effective the framework is in achieving the aims of the group. In conclusion it
      articulates the hope that this work will improve the care which is shown to all
      recipients of health care whatever their cultural background.

PMID- 22981888
TI  - Should we individualize breast cancer screening?
AB  - Publicly organized population breast cancer screening is presently hotly debated.
      Indeed, population screening is poorly effective, induces harms in a healthy
      population and is costly. However, stopping all kind of screening of low- and
      average-risk women would be problematic as about 70% of breast cancers are
      diagnosed in those subgroups, and maintaining current population screening in
      high-risk women would be insufficient. We propose herein a review about the
      advantages and the inconvenience of individualized screening. The latter could be
      a more efficient strategy. The principles of individualized screening are (a) to
      start from the age at which the breast cancer risk is equal to that for an
      average women aged 50 years, (b) to stop when the risk of co-mortality exceeds
      the risk of breast cancer mortality, (c) to adapt the exams frequency and the
      imaging modalities to the individual risk and to the breast density, (d) to
      reassess regularly and individually the screening strategy, and (e) to discuss
      honestly with each woman in order to help her to decide if she participates or
      not.

PMID- 22981889
TI  - Enhanced expression of IL-10 in contrast to IL-12B mRNA in poultry with
      experimental coccidiosis.
AB  - Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with an antagonistic
      effect on the T-helper (Th)1/Th2 cytokine balance and they provide a functional
      link between innate resistance and the adaptive immune response. This
      investigation was conducted to determine the expression of IL-10 and IL-12B mRNA
      levels in chickens' gut mucosa infected with Eimeria tenella and in
      sulfachlorpyrazine-sodium treated animals after infection. Broiler chickens were
      randomly allocated in three groups: healthy untreated control; infected untreated
      animals and infected, treated with sulfachlorpyrazine sodium chickens 6 days
      after the challenge with an E. tenella. Quantitative real time PCR analysis was
      performed using specific primer pairs and probes for IL-10 and IL-12B. The
      expression of IL-10 mRNA was greater in the duodenum then in the caecum and the
      liver of healthy chickens. E. tenella infection led to significant up-regulation
      of IL-10 mRNA in the caecum, followed by mRNA in the liver. A significant down
      regulation was observed mainly in the caecum after the treatment with
      sulfachlorpyrazine. In contrast, IL-12B expression in all investigated tissues
      remained insignificantly affected in the studied groups of animals. Distinct up
      regulation of IL-10 mRNA, after the challenge with E. tenella, in the caecum can
      be attributed to the tissue tropism of Eimeria spp. The production of IL-12 is
      regulated by negative feedback through IL-10 which explains lack of increase in
      IL-12B mRNA. Sulfonamide treatment resulted in clinical improvement and
      restoration of IL-10 mRNA to the levels observed in healthy chickens.

PMID- 22981890
TI  - An investigation of implicit memory through left temporal lobectomy for epilepsy.
AB  - Temporal lobe epilepsy patients have demonstrated a relative preservation in the
      integrity of implicit memory procedures. We examined performance in a verbal
      implicit and explicit memory task in left anterior temporal lobectomy patients
      (LATL) and healthy normal controls (NCs) while undergoing fMRI. We hypothesized
      that despite the relative integrity of implicit memory in both the LATL patients
      and normal controls, the two groups would show distinct functional neuroanatomic
      profiles during implicit memory. LATLs and NCs performed Jacoby's Process
      Dissociation Process (PDP) procedure during fMRI, requiring completion of word
      stems based on the previously studied words or new/unseen words. Measures of
      automaticity and recollection provided uncontaminated indices of implicit and
      explicit memory, respectively. The behavioral data showed that in the face of
      temporal lobe pathology implicit memory can be carried out, suggesting implicit
      verbal memory retrieval is non-mesial temporal in nature. Compared to NCs, the
      LATL patients showed reliable activation, not deactivation, during implicit
      (automatic) responding. The regions mediating this response were cortical (left
      medial frontal and precuneus) and striatal. The active regions in LATL patients
      have the capacity to implement associative, conditioned responses that might
      otherwise be carried out by a healthy temporal lobe, suggesting this represented
      a compensatory activity. Because the precuneus has also been implicated in
      explicit memory, the data suggests this structure may have a highly flexible
      functionality, capable of supporting implementation of either explicit memory, or
      automatic processes such as implicit memory retrieval. Our data suggest that a
      healthy mesial/anterior temporal lobe may be needed for generating the posterior
      deactivation perceptual priming response seen in normals.

PMID- 22981891
TI  - The value of comparative effectiveness research: projected return on investment
      of the RxPONDER trial (SWOG S1007).
AB  - OBJECTIVE: The objective of this study was to assess the value of research of the
      RxPONDER study, an ongoing comparative effectiveness RCT designed to evaluate a
      21-gene profile in early stage, node-positive breast cancer. METHODS: We
      developed a disease-based decision-analytic model to compare use of the 21-gene
      profile versus standard care. Key clinical data were derived from SWOG-8814, an
      RCT of chemotherapy in lymph node-positive breast cancer. Other model parameters
      were obtained from published sources. Probabilistic simulations and value of
      information calculations were used to assess the expected value of sample
      information (EVSI) and the expected value of sample parameter information
      (EVSPI). RESULTS: The cost of the RxPONDER trial is expected to be at least $27
      million. The expected value of research of the RxPONDER trial ranged from $450
      million to $1 billion, representing a return of 17 to 39 times the projected cost
      of the trial. The primary objective of RxPONDER, to assess survival, had the
      largest estimated value relative to other model inputs. The value of RxPONDER
      increased by $50 million to $100 million after stakeholder input on additional
      data collection. CONCLUSION: The RxPONDER study appears to represent a good
      investment of public research funds. Stakeholder engagement and assessment of the
      return on investment should be considered to optimize and quantify the value of
      comparative effectiveness studies.

PMID- 22981892
TI  - Effect of low-dose thalidomide on dopaminergic neuronal differentiation of human
      neural progenitor cells: a combined study of metabolomics and morphological
      analysis.
AB  - Thalidomide is increasingly used in anticancer and anti-inflammation therapies.
      However, it is known for its teratogenicity and ability to induce peripheral
      neuropathy, although the mechanisms underlying its neurological effect in humans
      are unclear. In this study, we investigated the effect of thalidomide on the
      metabolism and neuronal differentiation of human neural progenitor cells. We
      found that levels of tyrosine, phenylalanine, methionine and glutathione, which
      are involved in dopamine and methionine metabolism, were decreased following
      thalidomide treatment. Morphological analysis revealed that treatment with 100 nM
      thalidomide, which is much lower than clinical doses, significantly decreased the
      number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with
      control cells. Our results suggest that these adverse neurological effects of
      thalidomide should be taken into consideration prior to its use for the treatment
      of neurodegenerative and other diseases.

PMID- 22981893
TI  - Characterization of the antibody response elicited by immunization with
      pneumococcal surface protein A (PspA) as recombinant protein or DNA vaccine and
      analysis of protection against an intranasal lethal challenge with Streptococcus
      pneumoniae.
AB  - Pneumococcal surface protein A (PspA) is an important candidate for a vaccine
      against pneumococcal infections. DNA vaccines expressing PspA were shown to
      protect mice against intraperitoneal and colonization challenge models in mice.
      We now show that a DNA vaccine expressing PspA from clade 4 (pSec-pspA4Pro) is
      also able to elicit protection against an intranasal lethal challenge model at
      levels similar to the recombinant protein PspA4Pro adjuvanted with alum. PspA4Pro
      + alum induced an IgG response characterized by a high IgG1/IgG2a ratio, leading
      to a lack of binding of anti-PspA IgG2a antibodies to intact pneumococci in
      vitro, which is in contrast to the response elicited by pSec-pspA4Pro. Epitopes
      recognized by the sera were mapped and antibodies induced by immunization with
      PspA4Pro + alum showed positive reaction with several synthetic peptides, mostly
      located in the first half of the protein. On the other hand, antibodies induced
      by the DNA vaccine showed reactivity with only two peptides. Though both
      strategies were protective against the intranasal lethal challenge model, the
      elicited humoral responses differ significantly, with the detection of important
      differences in the Fc (IgG1/IgG2a ratios) and Fab (recognized epitopes) regions
      of the induced antibodies.

PMID- 22981894
TI  - Long-term high frequency deep brain stimulation of the nucleus accumbens drives
      time-dependent changes in functional connectivity in the rodent limbic system.
AB  - Deep brain stimulation of the ventral striatum is an effective treatment for a
      variety of treatment refractory psychiatric disorders yet the mechanism of action
      remains elusive. We examined how five days of stimulation affected rhythmic brain
      activity in freely moving rats in terms of oscillatory power within, and
      coherence between, selected limbic regions bilaterally. Custom made bipolar
      stimulating/recording electrodes were implanted, bilaterally, in the nucleus
      accumbens core. Local field potential (LFP) recording electrodes were implanted,
      bilaterally in the prelimbic and orbitofrontal cortices and mediodorsal thalamic
      nucleus. Stimulation was delivered bilaterally with 100 MUs duration constant
      current pulses at a frequency of 130 Hz delivered at an amplitude of 100 MUA
      using a custom-made stimulation device. Synchronized video and LFP data were
      collected from animals in their home cages before, during and after stimulation.
      Signals were processed to remove movement and stimulation artifacts, and analyzed
      to determine changes in spectral power within, and coherence between regions.
      Five days stimulation of the nucleus accumbens core yielded temporally dynamic
      modulation of LFP power in multiple bandwidths across multiple brain regions.
      Coherence was seen to decrease in the alpha band between the mediodorsal thalamic
      nucleus and core of the nucleus accumbens. Coherence between each core of the
      nucleus accumbens bilaterally showed rich temporal dynamics throughout the five
      day stimulation period. Stimulation cessation revealed significant "rebound"
      effects in both power and coherence in multiple brain regions. Overall, the
      initial changes in power observed with short-term stimulation are replaced by
      altered coherence, which may reflect the functional action of DBS.

PMID- 22981895
TI  - Feasibility study of B16 melanoma therapy using oxidized ATP to target purinergic
      receptor P2X7.
AB  - The P2X7 receptor is not only involved in cell proliferation, but also acts as an
      adenosine 5'-triphosphate (ATP)-gated non-selective channel, and its expression
      is increased in human melanoma. An irreversible antagonist of P2X7, such as
      oxidized ATP (oxATP), might block P2X7 receptor-mediated ATP release and
      proliferative signaling. Therefore, we carried out basic studies to test this
      idea and to examine the feasibility of using oxATP to treat B16 melanoma. We
      first found that low-pH conditions (mimicking the hypoxia and acidosis commonly
      seen in solid tumors) induced P2X7 receptor-mediated ATP release from B16
      melanoma cells. Then, we compared the proliferation rates of B16 melanoma wild
      type cells and B16 P2X7 receptor-knockdown clone (P2X7-KDC) cells in the presence
      of P2X7 agonists. The proliferation rate, as well as the ATP release, of agonist
      treated P2X7-KDC cells was lower than that of agonist-treated wild-type cells.
      Next, the effect of P2X7 antagonist oxATP on B16 melanoma cell growth was
      examined in vitro and in vivo. oxATP significantly decreased B16 melanoma cell
      proliferation in vitro, and also significantly inhibited tumor growth in B16
      melanoma-bearing mice. These data indicate that extracellularly released ATP may
      serve as an intercellular signaling molecule. We propose that the P2X7 receptor
      is a promising target for treatment of solid tumors.

PMID- 22981896
TI  - Reactive oxygen species sources and biomolecular oxidative damage induced by
      aflatoxin B1 and fumonisin B1 in rat spleen mononuclear cells.
AB  - Aflatoxin B1 (AFB(1)) and fumonisin B1 (FB(1)) are mycotoxins widely found as
      cereal contaminants. Their immunotoxicities predispose to infectious diseases and
      may alter the tumor immunosurveillance of human and animals, but the mechanisms
      underlying have not been fully elucidated, and the induction of oxidative stress
      has been proposed as a probable mechanism. This work was aimed at evaluating in
      spleen mononuclear cells (SMC) from Wistar rats the effects of the exposure, in
      vitro for up to 48 h, to 20 MUM AFB(1), 10 MUM FB(1) and AFB(1)-FB(1) mixture
      (MIX), over cellular oxidative status, as well as at elucidating the contribution
      of different reactive oxygen species (ROS) to biomolecular oxidative damage, the
      biochemical pathways involved, and the probable interaction of both toxins to
      induce oxidative stress. All the treatments increased total ROS and oxidation of
      biomolecules, with MIX having the greatest effects. However, only MIX increased
      superoxide anion radical. The main ROS involved in oxidation of proteins, lipids
      and DNA appear to be hydrogen peroxide and hydroxyl radical. The mitochondrial
      complex I and CYP450 were involved in the ROS generation induced by all
      treatments. The NADPH oxidase system was induced by FB1 and MIX. The arachidonic
      acid metabolism contributed to the ROS formation induced by AFB(1) and MIX. These
      results demonstrate that an interaction between AFB(1) and FB(1) occur in the
      oxidative stress induction, and show the biochemical pathways involved in ROS
      generation in SMC. The oxidative stress could mediate the AFB(1) and FB(1)
      individual and combined immunotoxicities.

PMID- 22981897
TI  - Response monitoring and cognitive control in childhood obesity.
AB  - The ability to discern when actions deviate from goals and adjust behavior
      accordingly is crucial for efforts at self-regulation, including managing one's
      weight. We examined whether children with obesity differed from controls in
      response monitoring, an aspect of cognitive control that involves registering
      one's errors. Participants performed a cognitive interference task, responding to
      the colors of arrows while ignoring their orientations, and error-related neural
      activity was indexed via response-locked event-related potentials (ERPs).
      Compared to controls, participants with obesity exhibited significantly blunted
      "error-related negativity", an ERP component linked to response monitoring.
      Participants with obesity also exhibited a marginally blunted "error-related
      positivity", an ERP component linked to late-stage error processing, as well as
      in behavioral indices of cognitive control. These results suggest that childhood
      obesity may be associated with reduced response monitoring and that this aspect
      of cognitive control may play an important role in health-related self-regulatory
      behavior.

PMID- 22981898
TI  - Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase
      2 (CALERIE Phase 2) screening and recruitment: methods and results.
AB  - The Comprehensive Assessment of the Long-term Effects of Reducing Intake of
      Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25%
      calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3
      clinical sites, one coordinating center), parallel group, randomized controlled
      trial. Participants were recruited, screened, and randomized to the CR or control
      group with a 2:1 allocation. Inclusion criteria included ages 21-50 years for men
      and 21-47 years for women, and a body mass index (BMI) of 22.0 <= BMI < 28.0
      kg/m(2). Exclusion criteria included abnormal laboratory markers, significant
      medical conditions, psychiatric/behavioral problems, and an inability to adhere
      to the rigors of the evaluation/intervention schedule. A multi-stage screening
      process (telephone screen and 3 in-clinic visits) was applied to identify
      eligible participants. Recruitment was effective and enrollment targets were met
      on time. 10,856 individuals contacted the clinical sites, of whom 9787 (90%)
      failed one or more eligibility criteria. Of the 1069 volunteers who started the
      in-clinic screening, 831 (78%) were either ineligible or dropped. 238 volunteers
      were enrolled (i.e., initiated the baseline evaluations), 220 were randomized,
      and 218 started the assigned intervention (2% from the first screening step).
      This study offered lessons for future multi-center trials engaging non-disease
      populations. Recruitment strategies must be tailored to specific sites. A multi
      disciplinary screening process should be applied to address medical, physical,
      and psychological/behavioral suitability of participants. Finally, a multi-step
      screening process with simple criteria first, followed by more elaborate
      procedures has the potential to reduce the use of study resources.

PMID- 22981899
TI  - Risk stratification and prognosis of acute cardiac events in hospitalized adults
      with community-acquired pneumonia.
AB  - OBJECTIVE: To determine the risk factors and the prognosis of acute cardiac
      events in patients with community-acquired pneumonia (CAP). METHODS:
      Observational analysis of a prospective cohort of hospitalized adults with CAP
      (1995-2010). A logistic regression analysis was performed to identify predictors
      for acute cardiac events and mortality. RESULTS: Of 3921 patients with CAP, 315
      (8%) had one or more acute cardiac events during hospitalization (199 new-onset
      or worsening cardiac arrhythmias, 118 new-onset or worsening congestive heart
      failure and/or 30 myocardial infarction). In the multivariate analysis, factors
      associated with these events were age >65 years, chronic heart disease, chronic
      kidney disease, tachycardia, septic shock, multilobar pneumonia, hypoalbuminemia,
      and pneumococcal pneumonia. A rule based on these variables had an area under ROC
      curve of 0.73 (95% CI 0.70-0.76) to predict acute cardiac events. These
      complications occurred in 2.8% of patients classified in the low-risk (<=3
      points), 9.7% in the intermediate-risk (4-5 points) and 21.2% in the high-risk
      (>=6 points) groups (P < .001). The overall case fatality rate was higher in
      patients who had acute cardiac events (19.4% vs. 6.4%; P < .001). CONCLUSION:
      Acute cardiac events occur frequently during hospitalization for CAP and are
      associated with poor prognosis. A simple rule based on demographic and clinical
      features may help identify patients at higher risk of these complications.

PMID- 22981900
TI  - High association of peroxiredoxins with lung cancer.

PMID- 22981901
TI  - Tobacco control: learning from Uruguay.

PMID- 22981902
TI  - Job strain as a measure of exposure to psychological strain.

PMID- 22981904
TI  - Tobacco control campaign in Uruguay: a population-based trend analysis.
AB  - BACKGROUND: In 2005, Uruguay initiated a series of comprehensive anti-smoking
      measures. We aimed to assess the effect of Uruguay's anti-tobacco campaign.
      METHODS: We did a population-based trend analysis, using neighbouring Argentina,
      which has not instituted such extensive anti-tobacco measures, as a control. We
      assessed three key endpoints in both countries: per-person consumption of
      cigarettes, as measured by tax records; the prevalence of tobacco use in
      adolescents, as measured by school-based surveys; and the prevalence of tobacco
      use in adults, as measured by nationwide household-based surveys. FINDINGS:
      During 2005-11, per-person consumption of cigarettes in Uruguay decreased by 4.3%
      per year (95% CI 2.4 to 6.2), whereas per-person consumption in Argentina
      increased by 0.6% per year (-1.2 to 2.5; p=0.002 for difference in trends).
      During 2003-09, the 30-day prevalence of tobacco use in Uruguayan students aged
      13 years, 15 years, and 17 years decreased by an estimated 8.0% per year (4.5 to
      11.6), compared with a decrease of 2.5% annually (0.5 to 4.5) in Argentinian
      students during 2001-09 (p=0.02 for difference in trends). From 2005 to 2011, the
      prevalence of current tobacco use in Uruguay decreased annually by an estimated
      3.3% (2.4 to 4.1), compared with an annual decrease in Argentina of 1.7% (0.8 to
      2.6; p=0.02 for difference in trends). INTERPRETATION: Uruguay's comprehensive
      tobacco-control campaign has been associated with a substantial, unprecedented
      decrease in tobacco use. Decreases in tobacco use in other low-income and middle
      income countries of the magnitude seen in Uruguay would have a substantial effect
      on the future global burden of tobacco-related diseases. FUNDING: J William
      Fulbright Foreign Scholarship Board and the US Department of State.

PMID- 22981903
TI  - Job strain as a risk factor for coronary heart disease: a collaborative meta
      analysis of individual participant data.
AB  - BACKGROUND: Published work assessing psychosocial stress (job strain) as a risk
      factor for coronary heart disease is inconsistent and subject to publication bias
      and reverse causation bias. We analysed the relation between job strain and
      coronary heart disease with a meta-analysis of published and unpublished studies.
      METHODS: We used individual records from 13 European cohort studies (1985-2006)
      of men and women without coronary heart disease who were employed at time of
      baseline assessment. We measured job strain with questions from validated job
      content and demand-control questionnaires. We extracted data in two stages such
      that acquisition and harmonisation of job strain measure and covariables occurred
      before linkage to records for coronary heart disease. We defined incident
      coronary heart disease as the first non-fatal myocardial infarction or coronary
      death. FINDINGS: 30,214 (15%) of 197,473 participants reported job strain. In
      1.49 million person-years at risk (mean follow-up 7.5 years [SD 1.7]), we
      recorded 2358 events of incident coronary heart disease. After adjustment for sex
      and age, the hazard ratio for job strain versus no job strain was 1.23 (95% CI
      1.10-1.37). This effect estimate was higher in published (1.43, 1.15-1.77) than
      unpublished (1.16, 1.02-1.32) studies. Hazard ratios were likewise raised in
      analyses addressing reverse causality by exclusion of events of coronary heart
      disease that occurred in the first 3 years (1.31, 1.15-1.48) and 5 years (1.30,
      1.13-1.50) of follow-up. We noted an association between job strain and coronary
      heart disease for sex, age groups, socioeconomic strata, and region, and after
      adjustments for socioeconomic status, and lifestyle and conventional risk
      factors. The population attributable risk for job strain was 3.4%.
      INTERPRETATION: Our findings suggest that prevention of workplace stress might
      decrease disease incidence; however, this strategy would have a much smaller
      effect than would tackling of standard risk factors, such as smoking. FUNDING:
      Finnish Work Environment Fund, the Academy of Finland, the Swedish Research
      Council for Working Life and Social Research, the German Social Accident
      Insurance, the Danish National Research Centre for the Working Environment, the
      BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical
      Research Council, the Wellcome Trust, and the US National Institutes of Health.

PMID- 22981906
TI  - Benefit-risk assessment of plant sterols in margarine: a QALIBRA case study.
AB  - This paper presents the benefit-risk assessment of adding plant sterols to
      margarine as an illustration of the QALIBRA method and software. With the QALIBRA
      tool health effects, risks as well as benefits are expressed in a common metric
      (DALY) which allows quantitative balancing of benefits and risks of food intake.
      The QALIBRA software can handle uncertainties in a probabilistic simulation. This
      simple case study illustrates the data need and assumptions that go into a
      quantitative benefit-risk assessment. The assessment shows that the benefits of
      plant sterols added to margarine outweigh the risks, if any.

PMID- 22981905
TI  - TAK1 ubiquitination regulates doxorubicin-induced NF-kappaB activation.
AB  - Chemotherapeutic agents- and radiation therapy-induced NF-kappaB activation in
      cancer cells contributes to aggressive tumor growth and resistance to
      chemotherapy and ionizing radiation during cancer treatment. TAK1 has been shown
      to be required for genotoxic stress-induced NF-kappaB activation. However,
      whether TAK1 ubiquitination is involved in genotoxic stress-induced NF-kappaB
      activation remains unknown. Herein, we demonstrate that TAK1 ubiquitination plays
      an important role in the positive and negative regulation of doxorubicin (Dox)
      induced NF-kappaB activation. We found that TAK1 was required for Dox-induced NF
      kappaB activation. At the early stage of Dox treatment, Dox induced Lys63-linked
      TAK1 polyubiquitination at lysine 158 residue. USP4 inhibited Dox-induced TAK1
      Lys63-linked polyubiquitination and knockdown of USP4 enhanced Dox-induced NF
      kappaB activation. At the late stage of Dox treatment, Dox induced Lys48-linked
      TAK1 polyubiquitination to promote TAK1 degradation. ITCH inhibited Dox-induced
      NF-kappaB activation by promoting Lys48-linked TAK1 polyubiquitination and its
      subsequent degradation. Our study indicates that TAK1 ubiquitination plays
      critical roles in the regulation of Dox-induced NF-kappaB activation. Thus,
      intervention of TAK1 kinase activity or TAK1 Lys63-linked polyubiquitination
      pathways might greatly enhance the therapeutic efficacy of Dox.

PMID- 22981907
TI  - Estimation of cancer risks and benefits associated with a potential increased
      consumption of fruits and vegetables.
AB  - The current paper provides an analysis of the potential number of cancer cases
      that might be prevented if half the U.S. population increased its fruit and
      vegetable consumption by one serving each per day. This number is contrasted with
      an upper-bound estimate of concomitant cancer cases that might be theoretically
      attributed to the intake of pesticide residues arising from the same additional
      fruit and vegetable consumption. The cancer prevention estimates were derived
      using a published meta-analysis of nutritional epidemiology studies. The cancer
      risks were estimated using U.S. Environmental Protection Agency (EPA) methods,
      cancer potency estimates from rodent bioassays, and pesticide residue sampling
      data from the U.S. Department of Agriculture (USDA). The resulting estimates are
      that approximately 20,000 cancer cases per year could be prevented by increasing
      fruit and vegetable consumption, while up to 10 cancer cases per year could be
      caused by the added pesticide consumption. These estimates have significant
      uncertainties (e.g., potential residual confounding in the fruit and vegetable
      epidemiologic studies and reliance on rodent bioassays for cancer risk). However,
      the overwhelming difference between benefit and risk estimates provides
      confidence that consumers should not be concerned about cancer risks from
      consuming conventionally-grown fruits and vegetables.

PMID- 22981908
TI  - Comparative study of different Portuguese samples of propolis: pollinic,
      sensorial, physicochemical, microbiological characterization and antibacterial
      activity.
AB  - The aim of this work was to study four propolis samples from Tras-os-Montes
      region of Portugal. The propolis samples' color was different, which pollen
      analysis showed to be due to different botanical sources: Populus sp., Pinus sp.,
      Quercus sp. and Castanea sativa. The data from physicochemical analysis
      (moisture, soluble and insoluble solids content, pH, conductivity, ash content,
      wax, total phenolics and flavonoids content) was treated using multivariate
      statistical tools as cluster heat map, principal components analysis and linear
      discriminant analysis with the purpose of classifying the sample accordingly to
      the botanical/geographical origin. The discriminant analysis was applied with
      stepwise to select the variables that most contribute to sample identification
      accordingly to pollinic profile. The cross-validation technique was applied,
      using the leave-one-out procedure, which showed good prediction capabilities of
      the samples. Microbiologically, the commercial quality was satisfactory, since
      the samples didn't contain deterioration or pathogenic microorganisms. All the
      samples studied presented antimicrobial activity against Methicillin-resistant
      Staphylococcus aureus, in a dose dependent way. The antimicrobial activity was
      strictly related to the physicochemical composition. This work will allow
      connecting a particular chemical propolis type to a specific type of biological
      activity, what is essential for the use in therapeutic applications.

PMID- 22981909
TI  - Acute and 30-day oral toxicity studies of administered carnosic acid.
AB  - PURPOSE: Increasing interest in carnosic acid (CA) is due to its pharmacological
      properties. The aim of this study was to evaluate the acute and 30-day oral
      toxicity of CA. METHODS: The acute oral toxicity study in Kuming mice design
      followed the OECD-guidelines 423, and a 30-day chronic oral toxicity study in
      Wistar rats based on the enhanced OECD test guideline 407 were performed.
      RESULTS: The oral lethal dose (LD50) for mice was 7100 mg/kg of body weight in
      the acute toxicity study. The histopathological changes were observed in the
      heart, liver and kidney for the survival mice treated with a single dose CA. For
      the sub chronic toxicity study, CA administered for 30 days produced slightly
      reductions in the weight gain pattern, which did not reach the significant level
      when compared with the control values. With respect to serum biochemistry test,
      decreased total serum protein levels, but conversely increased aspartate
      aminotransferase (AST) levels were detected in the high-dose and moderate-dose
      groups. Histopathologically, light pathological changes were observed in the
      heart, liver, and kidney of rats treated with the high-dose CA. CONCLUSION: The
      present work suggests that a short-term oral administration of CA has a
      relatively low toxicity profile.

PMID- 22981910
TI  - Temporal dynamics, spatial range, and transcriptional interpretation of the
      Dorsal morphogen gradient.
AB  - Dorsoventral pattern of Drosophila embryo is specified by the nuclear
      localization gradient of the transcription factor Dorsal. Genetic and genomic
      studies of this morphogen gradient provided important insights into spatial
      control of gene expression in development. Recent live imaging experiments
      revealed hitherto unappreciated dynamics of the Dorsal gradient and posed new
      questions about the mechanisms of its transcriptional interpretation. Some of
      these questions can be answered by models in which the morphogenetic capacity of
      the Dorsal gradient is potentiated by spatially uniform factors, such as Zelda, a
      transcription factor that plays a key role in the activation of zygotic
      transcription. Combinatorial effects of uniform and graded factors play an
      important role in the transcriptional and signaling cascades initiated by Dorsal
      and may explain differential positioning of gene expression borders by other
      morphogen gradients.

PMID- 22981911
TI  - Signal transduction pathways involving phosphatidylinositol 4-phosphate and
      phosphatidylinositol 4,5-bisphosphate: convergences and divergences among
      eukaryotic kingdoms.
AB  - Phosphoinositides are minor constituents of eukaryotic membranes but participate
      in a wide range of cellular processes. The most abundant and best characterized
      phosphoinositide species are phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)
      and its main precursor, phosphatidylinositol 4-phosphate (PI4P). PI4P and
      PI(4,5)P2 regulate various structural and developmental functions but are also
      centrally involved in a plethora of signal transduction pathways in all
      eukaryotic models. They are not only precursors of second messengers but also
      directly interact with many protein effectors, thus regulating their localisation
      and/or activity. Furthermore, the discovery of independent PI(4,5)P2 signalling
      functions in the nucleus of mammalian cells have open a new perspective in the
      field. Striking similarities between mammalian, yeast and higher plant
      phosphoinositide signalling are noticeable, revealing early appearance and
      evolutionary conservation of this intracellular language. However, major
      differences have also been highlighted over the years, suggesting that organisms
      may have evolved different PI4P and PI(4,5)P2 functions over the course of
      eukaryotic diversification. Comparative studies of the different eukaryotic
      models is thus crucial for a comprehensive view of this fascinating signalling
      system. The present review aims to emphasize convergences and divergences between
      eukaryotic kingdoms in the mechanisms underlying PI4P and PI(4,5)P2 roles in
      signal transduction, in response to extracellular stimuli.

PMID- 22981912
TI  - Fabrication of organic electrochemical transistor arrays for biosensing.
AB  - BACKGROUND: Organic electrochemical transistors (OECT) have been used as various
      types of biosensors with very high sensitivity. The OECTs show advantages of easy
      fabrication, low operational voltage, excellent flexibility and biocompatibility.
      METHODS: OECT arrays based on poly(3,4-ethylenedioxythiophene):poly(styrene
      sulfonate) (PEDOT:PSS) were fabricated in poly(ethylene glycol) (PEG) microwells
      by physical delamination. RESULTS: The OECTs show fast response time, stable
      channel current and excellent transistor characteristics. The PEG microwells can
      be used to trap cells on top of the OECTs, which will be important for the
      application of the OECT arrays as cell-based biosensors. GENERAL SIGNIFICANCE:
      This technique provides a feasible way for high-throughput cell analysis based on
      transistor arrays. This article is part of a Special Issue entitled Organic
      Bioelectronics-Novel Applications in Biomedicine.

PMID- 22981913
TI  - Photochemical internalization (PCI) of HER2-targeted toxins: synergy is dependent
      on the treatment sequence.
AB  - BACKGROUND: Photochemical internalization (PCI) is a modality for cytosolic
      release of drugs trapped in endocytic vesicles. The method is based upon
      photosensitizers localized in the membranes of endocytic vesicles which create
      membrane rupture upon light exposure by generating reactive oxygen species (ROS),
      predominantly singlet oxygen ((1)O(2)). METHODS: The human epidermal growth
      factor receptor 2 (HER2)-targeted immunotoxin (IT), trastuzumab-saporin, was
      evaluated in combination with PCI using TPCS(2a) (Amphinex(r)), a new
      photosensitizer approved for clinical use. RESULTS: PCI synergistically enhanced
      the cytotoxicity of trastuzumab-saporin on trastuzumab-resistant HER2(+) Zr-75-1
      cells. The PCI effect was only observed when the IT was administered prior to the
      photochemical treatment ("light after" strategy), while administration of a non
      targeted drug may equally well be performed after light exposure. Mechanistic
      studies showed reduced ligand-induced HER2 phosphorylation and receptor-mediated
      endocytosis after TPCS(2a)-PDT. Photochemical disruption of the cytoplasmic
      domain of HER2 was found to be induced by (1)O(2) generated both by
      photosensitizer located in the endocytic vesicles and in the outer leaflet of the
      plasma membrane. CONCLUSIONS: Administration of the HER2-targeted toxin prior to
      light exposure is a prerequisite for successful PCI-mediated delivery of HER2
      targeted toxins. GENERAL SIGNIFICANCE: PCI of HER2-targeted toxins is
      demonstrated as a highly effective treatment modality which may overcome
      trastuzumab resistance. The mechanistic studies of the lack of PCI effect of the
      "light first" procedure is of outermost importance when designing a clinical PCI
      treatment protocol for delivery of HER2-targeted therapies.

PMID- 22981914
TI  - Nodavirus infection induces a great innate cell-mediated cytotoxic activity in
      resistant, gilthead seabream, and susceptible, European sea bass, teleost fish.
AB  - Viral nervous necrosis (VNN) virus produces great mortalities in fish having
      susceptible and reservoir species between the most important marine aquaculture
      species. Cell-mediated cytotoxicity (CMC) is considered, towards the interferon
      (IFN), the most important mechanism of the immune response to fight against viral
      infections but it has been very scarcely evaluated. We aimed to evaluate the
      effects of VNNV infection in the reservoir gilthead seabream (Sparus aurata) and
      susceptible European sea bass (Dicentrarchus labrax). Firstly, after experimental
      infection we found mortalities in the sea bass (55%) but no in the seabream.
      Moreover, VNN virus replicates in the brain of both species as it was reflected
      by the high up-regulation of the Mx gene expression. Interestingly, the head
      kidney leucocyte cell-mediated cytotoxic activity was significantly increased in
      both species reaching highest activity at 7 days: 3.65- and 2.7-fold increase in
      seabream and sea bass, respectively. This is supported by the significant up
      regulation of the non-specific cytotoxic cell receptor (NCCRP-1) in the two fish
      species. By contrast, phagocytosis was unaffected in both species. The
      respiratory burst was increased in seabream 7 days post-infection whilst in sea
      bass this activity was significantly decreased at days 7 and 15. Our results
      demonstrate the significance of the CMC activity in both gilthead seabream and
      European sea bass against nodavirus infections but further studies are still
      needed to understand the role of cytotoxic cells in the antiviral immune response
      and the mechanisms involved in either reservoir or susceptible fish species.

PMID- 22981915
TI  - Functional characterization of TNF-alpha in grass carp head kidney leukocytes:
      induction and involvement in the regulation of NF-kappaB signaling.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent regulatory cytokine, which
      serves as a key mediator of inflammation, immunity and apoptosis in mammals.
      Identification, expression and regulatory effects of TNF-alpha have been reported
      in various fish species, showing the structural and functional similarity or
      discrepancy between each other. In this study, TNF-alpha was identified from
      grass carp (Ctenopharyngodon idella) and the deduced grass carp TNF-alpha (gcTNF
      alpha) protein possessed the TNF family signature motifs, a protease cleavage
      site, a transmembrane domain and two conserved cysteine residues. Further studies
      showed that gcTNF-alpha expression was induced with a rapid kinetics by immune
      challenge in vitro and in vivo. To characterize the function of gcTNF-alpha,
      recombinant gcTNF-alpha (rgcTNF-alpha) was prepared by using the Escherichia coli
      expression system. It was shown to enhance the mRNA expression of gcTNF-alpha and
      gcIL-1beta in head kidney leukocytes (HKLs), confirming the biological activity
      of rgcTNF-alpha. In the same model, NF-kappaB inhibitor (PDTC) was able to
      attenuate rgcTNF-alpha-induced gcTNF-alpha mRNA expression, implying the
      involvement of NF-kappaB pathway in fish TNF-alpha action. This notion was
      reinforced by the finding that rgcTNF-alpha could induce the phosphorylation of
      IkappaBalpha in a time-dependent oscillation in HKLs, indicating a dynamical
      variation of NF-kappaB activity as seen in mammals. In addition, rgcTNF-alpha
      could up-regulate the expression of two TNF receptor-associated factors (TRAF),
      TRAF1 and TRAF2, in a time- and dose-dependent manner, suggesting that gcTNF
      alpha may function as a regulator of fish NF-kappaB pathway. These results for
      the first time reveal the link of gcTNF-alpha to the NF-kappaB pathway and
      provide a better understanding of TNF-alpha signaling in teleost immunity.

PMID- 22981916
TI  - [The role of a systematic second look at 48-72 hours in high-pressure injection
      injuries to the hand: a retrospective study].
AB  - OBJECTIVES: Poorly standardized, the management of high pressure injections (HPI)
      is frequently too late and inadequate, some teams reporting up to 50% of
      amputations. HPI causes inoculation of toxic particles in depth, particularly
      difficult to remove surgically. The persistence of this foreign material
      maintains local inflammation and increases the risk of infection. The objective
      of this article is to validate the benefit of a systematic "second look" at 48-72
      hours in HPI. METHODS: We conducted a retrospective study from 2006 to 2010, of
      patients who had a HPI into the hand. All patients had initial debridement
      surgery and a "second look" was systematically performed at 48-72 hours. RESULTS:
      During this period, six patients were treated for a HPI of paint (n=4) or oil
      (n=2). The time between the accident and surgery was 12.4 hours (2-24). Four
      patients had good functional outcome with no disabling sequelae. We performed two
      amputations. At six months, five patients returned to work. CONCLUSIONS: Early
      management determines the prognosis of the HPI. Extended debridement within six
      hours showed a better functional outcome than later treatment. Performing a
      systematic "second look" allows further washing/debridement and gives the
      possibility to be more conservative during the initial procedure. This second
      debridement allows excision of the newly formed necrosis and to evacuate the
      remaining toxic residues. Finally, patients reported good functional outcome.

PMID- 22981917
TI  - ANN multiplexing model of drugs effect on macrophages; theoretical and flow
      cytometry study on the cytotoxicity of the anti-microbial drug G1 in spleen.
AB  - Multiplexed biological assays provide multiple measurements of cellular
      parameters in the same test. In this work, we have trained and tested an
      Artificial Neural Network (ANN) model for the first time, in order to perform a
      multiplexing prediction of drugs effect on macrophage populations. In so doing,
      we have used the TOPS-MODE approach to calculate drug molecular descriptors and
      the software STATISTICA to seek different ANN models such as: Linear Neural
      Network (LNN), Radial Basis Function (RBF), Probabilistic Neural Networks (PNN)
      and Multi-Layer Perceptrons (MLP). The best model found was the LNN, which
      correctly classified 8258 out of 9000 (Accuracy = 93.0%) multiplexing assay
      endpoints of 7903 drugs (including both training and test series). Each endpoint
      corresponds to one out of 1418 assays, 36 molecular or cellular targets, 46
      standard type measures, in two possible organisms (human and mouse). Secondly, we
      have determined experimentally, for the first time, the values of EC(50) = 11.41
      MUg/mL and Cytotoxicity = 27.1% for the drug G1 over Balb/C mouse spleen
      macrophages using flow cytometry. In addition, we have used the LNN model to
      predict the G1 activity in 1265 multiplexing assays not measured experimentally
      (including 152 cytotoxicity assay endpoints). Both experimental and theoretical
      results point out a low macrophage cytotoxicity of G1. This work breaks new
      ground for the 'in silico' multiplexing screening of large libraries of
      compounds. The results obtained are very significant because they complement the
      immunotoxicology studies of this important anti-microbial/anti-parasite drug.

PMID- 22981918
TI  - On the pulmonary toxicity of oxygen. 5. Electronic structure and the paramagnetic
      property of oxygen.
AB  - Oxygen uptake by the pulmonary circulation is a chemical reaction. The
      physicochemical attributes of oxygen are critical when studying pulmonary oxygen
      toxicity. Extent of lung injury depends on the percentage of oxygen in an oxygen
      nitrogen mix in polybaric circumstances (Shanklin, 1969). Further change in
      extent of lesion follows when other gases are used in the inhalant mix instead of
      nitrogen (Shanklin and Lester, 1972), with oxygen at 21-100% of the mix.
      Comparative subatmospheric oxygen levels down to 3% in hydrogen, helium,
      nitrogen, argon, or sulfur hexafluoride, were run with and without ventilatory
      distress by the Farber (1937) model, bilateral cervical vagotomy (BCV). This
      yielded coherent results indicating a need to consider molecular characteristics
      at the atomic level. Molecular mass and size, gas viscosity, and thermal
      conductivity yielded no obvious correlates to lung injury. Saturation of the
      outer electron shells of the diluents fit the empiric data, prospectively an
      interaction between oxygen and nitrogen from their electronegativity and closely
      approximate molecular mass, size, and shape. The lesion is essentially eliminated
      at 7% oxygen in nitrogen. At 3% oxygen, the least lesion is found with N(2),
      H(2), and SF(6), all gases with incomplete outer electron shells, allowing for
      transient, possibly polarized, covalent bonding with oxygen as the significant
      minority component in the mix. Argon and helium do not interfere with oxygen.
      With 3% oxygen in argon without BCV, the experiments ran so long (>70hours) they
      were terminated once the point had been made. 3% oxygen in argon after BCV
      yielded a mean survival more than twice that of BCV in air, indicating a
      remarkable degree of nitrogen interference with oxygen in the respiratory medium
      of terrestrial animal life. Argon displayed other advantages for the lung
      compared to nitrogen. Hydrogen, nitrogen, and oxygen are diatomic molecules, a
      feature which does relate to the extent of lung injury, but only oxygen is
      paramagnetic. Magnetic effects on lesion formation were tested: [1] with
      ventilatory distress induced in newborn rabbits, and [2] in young adult female
      white mice exposed to 100% oxygen without added mechanical distress. A
      noninvasive model for ventilatory distress, thoracic restraint (TR), with longer
      mean survivals of 40-50hours, was employed rather than the Farber model. Parallel
      runs with TR, one subset receiving 100% oxygen in a plastic chamber resting on
      six strong ring magnets with measured fields up to +1200 gauss, the other plain
      100% oxygen, were performed. Both subsets developed moderate metabolic acidosis
      with average weight losses circa 25%, but over different time courses, 82.89+/
      4.91hours in magnetized oxygen, 55.4% longer than the 53.34+/-9.82hours in plain
      oxygen (p<0.001). The longer survival in magnetized oxygen meant extensive lung
      injury (99.57+/-0.42% pleural surface, versus 83.86+/-14.03%), but the rate of
      lesion formation was 30.89% faster in plain oxygen (1.5722% per hour) than in
      magnetized oxygen (1.2012% per hour), a difference significant at p<0.001. The
      effect of oxygen without mechanical ventilatory distress was examined in female
      adult white mice exposed to oxygen or magnetized oxygen. Similar survivals and
      weight losses were achieved. The rate of lung lesion formation was different,
      1.2617% per hour in plain oxygen, 46.13% faster than 0.8634% per hour in
      magnetized oxygen. A variable magnetic field, with animals moving and breathing
      in chambers flooded with oxygen, has both systemic and pulmonary effects which
      alter the rate of lesion formation due to oxygen toxicity. Paramagnetic oxygen in
      a magnetic field influences the effect of oxygen toxicity on the lung but at
      these strengths of field it does not overcome significant mechanical disturbance.

PMID- 22981919
TI  - MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria
      parva infected lymphocytes.
AB  - Our efforts are concerned with identifying features of incomplete malignant
      transformation caused by non viral pathogens. Theileria parva (T. parva) is a
      tick-transmitted protozoan parasite that can cause a fatal lymphoproliferative
      disease in cattle. The T. parva-infected lymphocytes display a transformed
      phenotype and proliferate in culture media like the other tumor cells, however
      those cells will return to normal after antiprotozoal treatment reflecting the
      incomplete nature of transformation. To identify signaling pathways involved in
      this form of transformation of T. parva-infected cells, we screened a library of
      anticancer compounds. Among these, TIBC, a specific inhibitor of MDM2, markedly
      inhibited proliferation of T. parva-infected lymphocytes and promoted apoptosis.
      Therefore we analyzed MDM2 function in T. parva-infected cells. Several T. parva
      infected cell lines showed increased expression level of MDM2 with alternatively
      spliced isoforms compared to the lymphoma cells or ConA blasts. In addition,
      buparvaquone affected MDM2 expression in T. parva transformed cells. Moreover,
      p53 protein accumulation and function were impaired in T. parva-infected cells
      after cisplatin induced DNA damage despite the increased p53 transcription level.
      Finally, the treatment of T. parva-infected cells with boronic-chalcone
      derivatives TIBC restored p53 protein accumulation and induced Bax expression.
      These results suggest that the overexpression of MDM2 is closely linked to the
      inhibition of p53-dependent apoptosis of T. parva-infected lymphocytes. Aberrant
      expression of host lymphocyte MDM2 induced by cytoplasmic existence of T. parva,
      directly and/or indirectly, is associated with aspects of this type of
      transformation of T. parva-infected lymphocytes. This form of transformation
      shares features of oncogene induced malignant phenotype acquisition.

PMID- 22981920
TI  - KCNIP4 as a candidate gene for personality disorders and adult ADHD.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      in children with striking persistence into adulthood and a high co-morbidity with
      other psychiatric disorders, including personality disorders (PD). The 4p15.31
      region was shown to be associated with ADHD in several genome wide association
      studies (GWAS). In the present study we also report association of the 4p15.31
      locus with Cluster B and Cluster C PD as identified by a pooled genome-wide
      association study in 400 individuals suffering from PD. The gene coding for the
      Kv channel-interacting protein 4 (KCNIP4) is located in this region. KCNIP4 is an
      interaction partner of presenilin and plays a role in a negative feedback loop in
      the Wnt/beta-catenin pathway. Thus, we reasoned it to be a promising candidate
      gene for ADHD as well as for PD. To clarify the role of KCNIP4 in those
      disorders, we conducted candidate gene based association studies in 594 patients
      suffering from adult ADHD and 630 PD patients as compared to 974 healthy control
      individuals. In the adult ADHD sample, six single markers and one haplotype block
      revealed to be associated with disease (p values from 0.0079 to 0.049). Seven
      markers within the KCNIP4 gene showed an association with PD (p values from
      0.0043 to 0.0437). The results of these studies suggest a role of KCNIP4 in the
      etiology of ADHD, PD and other co-morbid disorders.

PMID- 22981921
TI  - A simple spatiotemporal rabies model for skunk and bat interaction in northeast
      Texas.
AB  - We formulate a simple partial differential equation model in an effort to
      qualitatively reproduce the spread dynamics and spatial pattern of rabies in
      northeast Texas with overlapping reservoir species (skunks and bats). Most
      existing models ignore reservoir species or model them with patchy models by
      ordinary differential equations. In our model, we incorporate interspecies rabies
      infection in addition to rabid population random movement. We apply this model to
      the confirmed case data from northeast Texas with most parameter values obtained
      or computed from the literature. Results of simulations using both our skunk-only
      model and our skunk and bat model demonstrate that the model with overlapping
      reservoir species more accurately reproduces the progression of rabies spread in
      northeast Texas.

PMID- 22981922
TI  - The impact and interplay of long and short branches on phylogenetic information
      content.
AB  - In molecular systematics, evolutionary trees are reconstructed from sequences at
      the tips under simple models of site substitution. A central question is how much
      sequence data is required to reconstruct a tree accurately? The answer depends on
      the lengths of the branches (edges) of the tree, with very short and very long
      edges requiring long sequences for accurate tree inference, particularly when
      these branch lengths are arranged in certain ways. For four-taxon trees, the
      sequence length question has been investigated for the case of a rapid speciation
      event in the distant past. Here, we generalize results from this earlier study,
      and show that the same sequence length requirement holds even when the speciation
      event is recent, provided that at least one of the four taxa is distantly related
      to the others. However, this equivalence disappears if a molecular clock applies,
      since the length of the long outgroup edge becomes largely irrelevant in the
      estimation of the tree topology for a recent divergence. We also discuss briefly
      some extensions of these results to models in which substitution rates vary
      across sites and to settings where more than four taxa are involved.

PMID- 22981923
TI  - Wind effects on bounding flight.
AB  - The effects of the wind on the energy expenditure of bounding flight and on the
      travelling speed are dealt with. For this purpose, a mathematical model of
      bounding flight in moving air is developed. Introducing an appropriate non
      dimensionalization, results and findings of generally valid nature are derived.
      It is shown that bounding flight yields a flight mechanical advantage in
      headwinds when compared with continuous flapping flight. This is because the
      minimum energy expenditure is lower and the associated travelling speed is
      higher. The body lift in the bound phase has an advantageous influence. The
      effects of tailwinds yield less differences between bounding flight and
      continuous flapping flight.

PMID- 22981924
TI  - Neutrophil dynamics after chemotherapy and G-CSF: the role of pharmacokinetics in
      shaping the response.
AB  - Chemotherapy has profound effects on the hematopoietic system, most notably
      leading to neutropenia. Granulocyte colony stimulating factor (G-CSF) is often
      used to deal with this neutropenia, but the response is highly variable. In this
      paper we examine the role of pharmacokinetics and delivery protocols in shaping
      the neutrophil responses to chemotherapy and G-CSF. Neutrophil responses to
      different protocols of chemotherapy administration with varying dosages, infusion
      times, and schedules are studied through a mathematical model. We find that a
      single dose of chemotherapy produces a damped oscillation in neutrophil levels,
      and short-term applications of chemotherapy can induce permanent oscillations in
      neutrophil level if there is a bistability in the system. In addition, we confirm
      previous findings [Zhuge et al., J. Theor. Biol., 293(2012), 111-120] that when
      periodic chemotherapy is given, there is a significant period of delivery that
      induces resonance in the system and exacerbates the corresponding neutropenia.
      The width of this resonant period peak increases with the recovery rate after a
      single chemotherapy, which is given by the real part of the dominant eigenvalue
      pair at the steady state, and both are determined by a single cooperativity
      coefficient in the feedback function for the neutrophils. Our numerical studies
      show that the neutropenia caused by chemotherapy can be overcome if G-CSF is
      given early after chemotherapy but can actually be worsened if G-CSF is given
      later, consistent with results reported in Zhuge et al. (2012). The nadir in
      neutrophil level is found to be more sensitive to the dosage of chemotherapy than
      that of the G-CSF. Furthermore, dependence of our results with changes in key
      pharmacokinetic parameters as well as initial functions are studied. Thus, this
      study illuminates the potential for destructive resonance leading to neutropenia
      in response to periodic chemotherapy, and explores and explains why the timing of
      G-CSF is so crucial for successful reversal of chemotherapy induced neutropenia.

PMID- 22981926
TI  - Extensive intra-host genetic diversity uncovered in Cryptosporidium parvum using
      Next Generation Sequencing.
AB  - The theory about the Cryptosporidium life cycle predicts genetic diversity of
      sporozoites within the host. Nevertheless, the Cryptosporidium intra-host genetic
      diversity is difficult to study using conventional Sanger sequencing or
      electrophoretic resolution of amplicons, due to the methods' inability to resolve
      mixtures of templates. We analysed the within-isolate genetic diversity of two
      Cryptosporidium parvum isolates sharing common descent, by combining the use of
      Next Generation Sequencing and cloning of PCR amplicons with database searches.
      The analysis focused on the single-copy 70 kDa heat shock protein (HSP70) and the
      60kDa surface glycoprotein (gp60) genes, which allowed any diversity to be
      ascribed to the presence of a heterogeneous population of sporozoites. The
      results indicated an unprecedented intra-host genetic diversity, with two HSP70
      and 10 gp60 alleles in these isolates, in spite of the initial resolution of one
      allele per locus using Sanger sequencing. At both loci, the predominant alleles
      were those initially identified by Sanger sequencing. A significant (p<0.01)
      overrepresentation of gp60 alleles previously reported in New Zealand was
      observed. These results further our understanding of the genetic structure of C.
      parvum populations, and expose the limitations of the use of non-axenic isolates
      as operational taxonomic units of genetic studies of cryptosporidiosis.

PMID- 22981927
TI  - Genetic characterisation of Cryptosporidium and Giardia from dairy calves:
      discovery of species/genotypes consistent with those found in humans.
AB  - Cryptosporidium and Giardia are important genera of parasitic protists that can
      cause significant diarrhoeal diseases in humans and other animals. Depending on
      the species/genotype of parasite, human infection may be acquired via
      anthroponotic or zoonotic transmission routes. Here, we undertook a molecular
      epidemiological investigation of these two genera of parasites in pre- and post
      weaned calves from eight locations in Canterbury, New Zealand, by PCR-coupled
      sequencing and phylogenetic analysis of sequence data for regions in the 60 kDa
      glycoprotein (pgp60) gene of Cryptosporidium and/or the triose-phosphate
      isomerase (ptpi) gene of Giardia. The pgp60 and ptpi regions were specifically
      amplified from 15 (8.3%) and 11 (6.1%) of the 180 individual faecal samples,
      respectively. The sequences derived from all of the amplicons were aligned with
      homologous reference sequences and subjected to phylogenetic analysis by Bayesian
      inference. For Cryptosporidium, three samples contained Cryptosporidium parvum
      genotype IIa, subgenotypes IIaA15G3R1, IIaA19G3R1 and IIaA23G4. Twelve samples
      contained Cryptosporidium hominis genotype Ib, subgenotype IbA10G2R2. While
      subgenotypes IIaA15G3R1 and IIaA23G4 are new records, IIaA19G3R1 and IbA10G2R2
      are commonly found in humans in various countries. For Giardia, two samples
      contained Giardia duodenalis assemblage A, also common in humans. In contrast,
      nine samples contained G. duodenalis assemblage E, which is the first report of
      this assemblage in cattle in New Zealand. Therefore, the present results indicate
      that dairy calves on the South Island of New Zealand harbour 'zoonotic' genotypes
      of Cryptosporidium and Giardia, which is likely to have significant public health
      implications.

PMID- 22981928
TI  - Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug
      resistance and to improve therapeutic efficacy.
AB  - Leprosy remains a major public health problem, since single and multi-drug
      resistance has been reported worldwide over the last two decades. In the present
      study, we report the novel multi-targeted therapy for leprosy to overcome multi
      drug resistance and to improve therapeutic efficacy. If multiple enzymes of an
      essential metabolic pathway of a bacterium were targeted, then the therapy would
      become more effective and can prevent the occurrence of drug resistance. The
      MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were
      selected for multi targeted therapy. The conserved or class specific active site
      residues important for function or stability were predicted using evolutionary
      trace analysis and site directed mutagenesis studies. Ten such residues which
      were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and
      MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered
      based on their position in MurC) were found to be conserved in all the four Mur
      enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234
      and Y329 (numbered based on their position in MurE) were significant in binding
      substrates and/co-factors needed for the functional events in any three of the
      Mur enzymes. These are the probable residues for designing newer anti-leprosy
      drugs in an attempt to reduce drug resistance.

PMID- 22981929
TI  - Cationic influenza virosomes as an adjuvanted delivery system for CTL induction
      by DNA vaccination.
AB  - DNA vaccines have emerged as an attractive approach to induce CTL responses
      against cancer and infectious agents in recent years. Although CTL induction by
      DNA vaccination would be a valuable strategy for controlling viral infections,
      increasing the potency of DNA vaccines is mandatory before DNA vaccines can make
      it to the clinic. In this study, we developed and characterized a new and safe
      adjuvanted delivery system for DNA vaccination using cationic influenza virosomes
      (CIV). CIV were produced by reconstitution of detergent-solubilized influenza
      virus membranes in the presence of cationic lipids. Plasmid DNA (pDNA) mixed with
      these virosomes was efficiently transfected into cells of a mouse macrophage cell
      line (RAW-Blue cells). Moreover, the cells were effectively activated as
      demonstrated by production of an NFkappaB/AP-1-inducible reporter enzyme.
      Following three intradermal immunizations, CIV-delivered epitope-encoding pDNA
      induced equal numbers of IFNgamma- and granzyme B-producing T cells than a 10
      fold higher dose of naked pDNA. Virosomes without cationic lipids also improved
      induction of cellular immunity by pDNA but to a significantly lower extent than
      CIV. These findings suggest that pDNA-CIV complexes could be an efficacious
      delivery system suitable for CTL induction by DNA vaccination.

PMID- 22981930
TI  - Development of an Au/ZnO thin film surface plasmon resonance-based biosensor
      immunoassay for the detection of carbohydrate antigen 15-3 in human saliva.
AB  - OBJECTIVE: To evaluate a novel surface plasmon resonance (SPR) system for the
      direct measurement of tumor marker carbohydrate antigen 15-3 (CA15-3) in human
      saliva. DESIGN AND METHODS: We measured the presence of the tumor marker
      carbohydrate antigen 15-3 (CA15-3) in human saliva using 2 different surface
      plasmon resonance (SPR) systems. To compare the sensitivity of an SPR biosensor
      based on thin-film Au/ZnO and the Biacore SPR system, we prepared CA15-3 samples
      in saliva and analyzed intensity responses to the samples at various
      concentrations of CA15-3. RESULTS: The linear detection range of CA15-3 in human
      saliva with the SPR system based on thin-film Au/ZnO was 2.5-20 U/mL (the cut-off
      point in cancer patients is around 4 U/mL). The linear range with the Biacore SPR
      system was 40-300 U/mL. CONCLUSIONS: These results show that thin-film Au/ZnO
      based SPR systems have higher sensitivity and can be used for measuring the
      levels of CA15-3 in human saliva without concentrating the samples.

PMID- 22981931
TI  - Diagnostic power of the mid-regional pro-atrial natriuretic peptide for heart
      failure patients with dyspnea: a meta-analysis.
AB  - OBJECTIVE: To evaluate the diagnostic performance of the mid-regional portion of
      the pro-atrial natriuretic peptide (MR-proANP) for heart failure (HF) in dyspnea
      patients. DESIGN AND METHODS: We performed a systematic review of English
      language studies published during the past three decades. The performance
      characteristics (diagnostic sensitivity, specificity, and other measures of
      accuracy) were pooled and examined by random-effects models. RESULTS: Five
      studies met the inclusion criteria, which included 1153 patients with HF and 1904
      non-HF patients. The summary estimates for MR-proANP in HF diagnosis had a
      diagnostic sensitivity of 0.90 (95% confidence interval (CI), 0.88-0.92), a
      specificity of 0.68 (95% CI, 0.66-0.70), and a diagnostic odds ratio (DOR) of
      22.89 (95% CI, 12.54-41.77). The area under the curve (AUC) and Q value for the
      summary receiver operating characteristic (sROC) curves were 0.88 and 0.81,
      respectively. CONCLUSION: MR-proANP showed a high diagnostic accuracy for HF in
      dyspnea patients.

PMID- 22981932
TI  - Prognostic value of miR-29a expression in pediatric acute myeloid leukemia.
AB  - OBJECTIVES: As a member of miR-29 family, miR-29a can act as either oncogene or
      tumor suppressor. However, its expression patterns in acute myeloid leukemia
      (AML) are controversial according to previous studies. Thus, the aim of this
      study was to determine the expression and clinical significance of miR-29a in
      pediatric AML. METHODS: Expression levels of miR-29a in bone marrow mononuclear
      cells were detected by real-time quantitative PCR in a cohort of 106 patients
      with newly diagnosed pediatric AML. The prognostic values of miR-29a in pediatric
      AML were also analyzed. RESULTS: Compared with normal controls, we demonstrated a
      significantly decreased expression of miR-29a in the bone marrow of pediatric AML
      patients (P<0.001). The expression levels of miR-29a were significantly lower in
      French-American-British classification subtype M7 than in other subtypes
      (P<0.001) and differed significantly across cytogenetic risk groups (P=0.002)
      with high miR-29a expression among those with favorable karyotypes. Moreover, low
      miR-29a expression was significantly associated with shorter relapse-free
      (P<0.001) and overall (P=0.008) survival in pediatric AML patients. Cox
      proportional hazards multivariate analysis of the univariate predictors
      identified cytogenetic risk and miR-29a expression as independent prognostic
      factors for relapse-free survival and overall survival. More interestingly, the
      prognostic value of miR-29a expression was more obvious in the subgroup of
      patients with intermediate-risk cytogenetics. CONCLUSION: Our data indicate for
      the first time that the down-regulation of miR-29a was associated with advanced
      clinical features and poor prognosis of pediatric AML patients, suggesting that
      miR-29a down-regulation may be used as an unfavorable prognostic marker in
      pediatric AML.

PMID- 22981934
TI  - Notch signals contribute to preserve the multipotentiality of human CD34(+)CD38(
      )CD45RA(-)CD90(+) hematopoietic progenitors by maintaining T cell lineage
      differentiation potential.
AB  - Notch signals are critical for T-cell development, limiting the differentiation
      potential of multipotent progenitors arriving in the thymus via the bloodstream.
      Notch ligands Delta-like and Jagged are expressed in the bone marrow and,
      consequently, a role in the regulation of early events of adult hematopoiesis has
      been proposed. However, mice with disruptions in the Notch pathway do not show
      gross defects in the hematopoietic stem cell compartment, limiting Notch effects
      at later stages of development. In this study, we identify cord blood
      CD34(+)CD38(-)CD45RA(-)CD90(+) cells, a recently described population of
      hematopoietic stem cells, as one of the earliest targets of Notch in human
      hematopoiesis. Upon Notch activation, CD34(+)CD38(-) cells are blocked in their
      differentiation at the CD34(+)CD38(-)CD45RA(-)CD90(+) stage. Importantly,
      population and clonal analysis demonstrate that Delta-like-1 exposure does not
      affect lymphoid vs myeloid decisions. However, Notch signaling is required before
      lymphoid commitment to preserve T-cell potential of CD34(+)CD38(-)CD45RA(
      )CD90(+) cells. Our experiments also show that in terms of differentiation
      potential, CD34(+)CD38(-)CD45RA(-)CD90(+) cells cultured in the presence of Notch
      signals, resemble cells directly isolated from cord blood. These results could
      have implications for translational efforts in the design of strategies aimed to
      accelerate immune reconstitution after transplantation.

PMID- 22981933
TI  - Differential roles of cAMP and cGMP in megakaryocyte maturation and platelet
      biogenesis.
AB  - The cyclic nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine
      monophosphate (cGMP) regulate the activity of protein kinase A (PKA) and protein
      kinase G (PKG), respectively. This process helps maintain circulating platelets
      in a resting state. Here we studied the role of cAMP and cGMP in the regulation
      of megakaryocyte (MK) differentiation and platelet formation. Cultured, platelet
      producing MKs were differentiated from fetal livers harvested from 13.5 days
      postcoital mouse embryos. MK development was accompanied by a dramatic increase
      in cAMP production and expression of soluble guanylate cyclase, PKG, and PKA as
      well as their downstream targets vasodilator-stimulated phosphoprotein (VASP) and
      MENA. Stimulation of prostaglandin E(1) receptor/adenylyl cyclase or soluble
      guanylate cyclase/PKG in cultured MKs increased VASP phosphorylation, indicating
      that these components share a common signaling pathway. To dissect out the role
      of cyclic nucleotides in MK differentiation, cAMP/PKA and cGMP/PKG signaling were
      alternately blocked in cultured MKs. Down-regulation of cAMP pathway effectors
      decreased MK numbers and ploidy. Notably, cGMP levels increased at the beginning
      of MK development and returned to basal levels in parallel with MK maturation.
      However, inhibition of cGMP pathway effectors had no effect on MK development. In
      addition, platelet release from mature MKs was enhanced by cGMP and inhibited by
      cAMP. Our data suggest that cAMP plays an important role in MK differentiation,
      while cAMP and cGMP have opposite effects on platelet production. Identifying the
      signaling pathways that underpin MK development and proplatelet formation will
      provide greater insights into thrombopoiesis and may potentially yield useful
      therapeutic targets.

PMID- 22981935
TI  - Classical and novel approaches to the preclinical testing of anxiolytics: A
      critical evaluation.
AB  - Over 80% of current anxiety studies employ one of the tests that were developed
      earlier than, or concurrently with the elevated plus-maze, i.e. before 1985.
      Considering 1985 as a historical reference point, we briefly review here 115 new
      tests and models of anxiety, the development of which was likely prompted by the
      poor predictive validity of classical tests as shown here by the comparison of
      preclinical and clinical findings with putative novel anxiolytics. The new
      approaches comprise major innovations to classical tests, the pre-test
      application of manipulations that mimic etiological factors of anxiety disorders,
      and entirely new approaches including anxiety disorder-specific tests. Thus,
      intensive test development over the last 27 years created a large pool of novel
      approaches. However, these are infrequently used and as such, their impact on
      anxiolytic drug development remains low. We suggest here that test/model
      development should step over the intensive phase when several new methods are
      proposed each year and should start selecting and establishing the methodologies
      that would successfully replace or complement classical tests. We propose here a
      novel strategy for improving the validity of anxiety testing that includes the
      retrospective analysis of the predictive validity of new procedures (as opposed
      to classical pharmacological validation), and a call for concerted international
      efforts at both the conceptual and practical levels. Similar endeavors proved
      recently successful with other psychiatric disorders.

PMID- 22981936
TI  - MRI-guided volume reconstruction of mouse brain from histological sections.
AB  - A method is presented for three-dimensional reconstruction of the mouse brain
      from histological sections with the guidance of magnetic resonance images (MRI).
      A major focus of the method is dealing with sections in which anatomical
      structures have been separated or distorted as a result of histological
      processing. Although histology has superb resolution with the ability to
      discriminate cell types and anatomical structures, misalignment between sections
      and distortion within sections renders 3D reconstruction of the histology volume
      simply by stacking 2D sections inadequate. In contrast, MRI preserves the spatial
      and geometric information about structures at a cost of cellular detail. To
      utilize the information from MRI in reconstructing volumetric histological data,
      we developed a procedure consisting of a series of segmentation and registration
      operations. The method is iterative and first identifies the corresponding MRI
      slices for each histological section. Piecewise rigid registration is then
      employed to deal with tissue distortion caused by histological processing.
      Quantitative validation of the method's accuracy was performed on four
      reconstructed mouse brains by comparing a set of manually selected anatomical
      landmarks on pairs of MRI and histological volumes. The procedure is highly
      automated and amenable to high throughput.

PMID- 22981937
TI  - FAT10 knock out mice livers fail to develop Mallory-Denk bodies in the DDC mouse
      model.
AB  - Mallory-Denk bodies (MDBs) are aggresomes composed of undigested ubiqutinated
      short lived proteins which have accumulated because of a decrease in the rate of
      their degradation by the 26s proteasome. The decrease in the activity of the
      proteasome is due to a shift in the activity of the 26s proteasome to the
      immunoproteasome triggered by an increase in expression of the catalytic subunits
      of the immunoproteasome which replaces the catalytic subunits of the 26s
      proteasome. This switch in the type of proteasome in liver cells is triggered by
      the binding of IFNgamma to the IFNgamma sequence response element (ISRE) located
      on the FAT10 promoter. To determine if either FAT10 or IFNgamma are essential for
      the formation of MDBs we fed both IFNgamma and FAT10 knock out (KO) mice DDC
      added to the control diet for 10weeks in order to induce MDBs. Mice fed the
      control diet and Wild type mice fed the DDC or control diet were compared. MDBs
      were located by immunofluorescent double stains using antibodies to ubiquitin to
      stain MDBs and FAT10 to localize the increased expression of FAT10 in MDB forming
      hepatocytes. We found that MDB formation occurred in the IFNgamma KO mice but not
      in the FAT10 KO mice. Western blots showed an increase in the ubiquitin smears
      and decreases beta 5 (chymotrypsin-like 26S proteasome subunit) in the Wild type
      mice fed DDC but not in the FAT10 KO mice fed DDC. To conclude, we have
      demonstrated that FAT10 is essential to the induction of MDB formation in the DDC
      fed mice.

PMID- 22981938
TI  - A patient with metastatic breast cancer 15 years after bilateral prophylactic
      total mastectomy and oophorectomy.

PMID- 22981939
TI  - A mother and daughter with phyllodes tumors of the breast.

PMID- 22981940
TI  - The Society of Pediatric Nurses: position statement on child welfare.

PMID- 22981941
TI  - Concussion: the hidden injury.

PMID- 22981942
TI  - Oxytocin-induced yawning: sites of action in the brain and interaction with
      mesolimbic/mesocortical and incertohypothalamic dopaminergic neurons in male
      rats.
AB  - Oxytocin (80 ng) induces yawning when injected into the caudal part of the
      ventral tegmental area, the hippocampal ventral subiculum and the posteromedial
      nucleus of the amygdala of male rats. The behavioural response occurred
      concomitantly with an increase in the concentration of extracellular dopamine and
      its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the dialysate
      obtained from the shell of the nucleus accumbens and of the prelimbic medial
      prefrontal cortex by means of intracerebral microdialysis. Both oxytocin
      responses were significantly reduced by d(CH2)5Tyr(Me)2-Orn8-vasotocin, a
      selective oxytocin receptor antagonist, injected in the above brain areas 15 min
      before oxytocin. Similar results were obtained by activating central
      oxytocinergic neurons originating in the paraventricular nucleus of the
      hypothalamus and projecting to the ventral tegmental area, the hippocampus and
      the amygdala, with the dopamine agonist apomorphine given at a dose that induces
      yawning when injected into the paraventricular nucleus. Since oxytocin is
      considered a key regulator of emotional and social reward that enhances amygdala
      dependent, socially reinforced learning and emotional empathy, mesolimbic and
      mesocortical dopamine neurons play a key role in motivation and reward, and
      yawning in mammals is considered a primitive, unconscious form of empathy, the
      present results support the hypothesis that oxytocinergic neurons originating in
      the paraventricular nucleus of the hypothalamus and projecting to the above brain
      areas and mesolimbic and mesocortical dopaminergic neurons participate in the
      complex neural circuits that play a role in the above mentioned functions.

PMID- 22981943
TI  - Act your age: tuning cell behavior to tissue requirements in interfollicular
      epidermis.
AB  - In all tissues the balance of cell proliferation and differentiation needs to be
      tuned to match the varying requirements of embryonic development and adult life.
      This is well illustrated by the interfollicular epidermis (IFE), which undergoes
      expansion and remodeling in utero, significant post natal growth and is then
      maintained in homeostasis. In addition to sustaining a high daily turnover of
      cells, the epidermis is able to re-populate areas of tissue damage due to common
      environmental stresses such as wounding. Here recent insights into proliferating
      cell behavior in IFE and how this changes through development and into adulthood
      are discussed.

PMID- 22981944
TI  - Elements of ribosomal drug resistance and specificity.
AB  - The structures of ribosomes in complex with inhibitors of translation have not
      only shed light on the interactions of antibiotics with the ribosome but also on
      the underlying mechanisms by which they interfere with the ribosome function.
      Several recent papers [1(*),2(**),3,4] have correlated the available ribosome
      structures with the wealth of biochemical data [5(*)]. In this review we shall
      focus on the lessons learned for drug specificity rather than presenting a
      comprehensive survey of the known structures of ribosome complexes with
      antibiotics.

PMID- 22981945
TI  - Longitudinal assessment of gait abnormalities following penetrating ballistic
      like brain injury in rats.
AB  - Traumatic brain injury (TBI) results in enduring motor and cognitive dysfunction.
      Although gait disturbances have been documented among TBI patients, few studies
      have profiled gait abnormalities in animal models of TBI. We sought to obtain a
      comprehensive longitudinal analysis of gait function following severe penetrating
      ballistic-like brain injury (PBBI) in rats. Rats were subjected to either
      unilateral frontal PBBI, probe insertion alone, or sham surgery. Sensorimotor
      performance was assessed using the CatWalk automated gait analysis system.
      Baseline measurements were taken 3 days prior to injury and detailed analysis of
      gait was performed at 1, 3, 7, 14, and 28 days post-injury. Both PBBI and probe
      inserted rats displayed altered static and dynamic gait parameters that were
      primarily evident during the early (<7 days) post-injury phase and were resolved
      by 1 month post-injury. PBBI produced more severe deficits compared to probe
      alone which were reflected in the number, magnitude, and resolution time of
      abnormal gait parameters. While altered parameters were detected in all four
      paws, they were more apparent on the contralateral side. Gait parameters
      including paw pressure, print area, swing speed, and stride length were
      significantly decreased whereas stance, swing, and step cycle duration were
      increased compared to sham. Overall, altered gait patterns detected using the
      CatWalk system in the PBBI model were injury-severity dependent, resolved at
      later time points, and appeared similar to those reported in severe TBI patients.
      These results indicate that the CatWalk may be most useful for neuroprotection
      studies that focus on the acute/subacute recovery period after TBI.

PMID- 22981946
TI  - POT1-TPP1 regulates telomeric overhang structural dynamics.
AB  - Human telomeres possess a single-stranded DNA (ssDNA) overhang of TTAGGG repeats,
      which can self-fold into a G-quadruplex structure. POT1 binds specifically to the
      telomeric overhang and partners with TPP1 to regulate telomere lengthening and
      capping, although the mechanism remains elusive. Here, we show that POT1 binds
      stably to folded telomeric G-quadruplex DNA in a sequential manner, one
      oligonucleotide/oligosaccharide binding fold at a time. POT1 binds from 3' to 5',
      thereby unfolding the G-quadruplex in a stepwise manner. In contrast, the POT1
      TPP1 complex induces a continuous folding and unfolding of the G-quadruplex. We
      demonstrate that POT1-TPP1 slides back and forth on telomeric DNA and also on a
      mutant telomeric DNA to which POT1 cannot bind alone. The sliding motion is
      specific to POT1-TPP1, as POT1 and ssDNA binding protein gp32 cannot recapitulate
      this activity. Our results reveal fundamental molecular steps and dynamics
      involved in telomere structure regulation.

PMID- 22981947
TI  - Allosteric mechanism controls traffic in the chaperone/usher pathway.
AB  - Many virulence organelles of Gram-negative bacterial pathogens are assembled via
      the chaperone/usher pathway. The chaperone transports organelle subunits across
      the periplasm to the outer membrane usher, where they are released and
      incorporated into growing fibers. Here, we elucidate the mechanism of the usher
      targeting step in assembly of the Yersinia pestis F1 capsule at the atomic level.
      The usher interacts almost exclusively with the chaperone in the
      chaperone:subunit complex. In free chaperone, a pair of conserved proline
      residues at the beginning of the subunit-binding loop form a "proline lock" that
      occludes the usher-binding surface and blocks usher binding. Binding of the
      subunit to the chaperone rotates the proline lock away from the usher-binding
      surface, allowing the chaperone-subunit complex to bind to the usher. We show
      that the proline lock exists in other chaperone/usher systems and represents a
      general allosteric mechanism for selective targeting of chaperone:subunit
      complexes to the usher and for release and recycling of the free chaperone.

PMID- 22981948
TI  - The crystal structure of the intact E. coli RelBE toxin-antitoxin complex
      provides the structural basis for conditional cooperativity.
AB  - The bacterial relBE locus encodes a toxin-antitoxin complex in which the toxin,
      RelE, is capable of cleaving mRNA in the ribosomal A site cotranslationally. The
      antitoxin, RelB, both binds and inhibits RelE, and regulates transcription
      through operator binding and conditional cooperativity controlled by RelE. Here,
      we present the crystal structure of the intact Escherichia coli RelB2E2 complex
      at 2.8 A resolution, comprising both the RelB-inhibited RelE and the RelB
      dimerization domain that binds DNA. RelE and RelB associate into a V-shaped
      heterotetrameric complex with the ribbon-helix-helix (RHH) dimerization domain at
      the apex. Our structure supports a model in which relO is optimally bound by two
      adjacent RelB2E heterotrimeric units, and is not compatible with concomitant
      binding of two RelB2E2 heterotetramers. The results thus provide a firm basis for
      understanding the model of conditional cooperativity at the molecular level.

PMID- 22981950
TI  - Differentiating the associations of black carbon and fine particle with daily
      mortality in a Chinese city.
AB  - There is only limited monitoring data of black carbon for epidemiologic analyses.
      In the current study, we used the distributed lag models to evaluate the
      association between mortality outcomes (both total and cause-specific) and
      exposure to black carbon and fine particle (PM(2.5)) in Shanghai, China. During
      our research period, the mean daily concentrations of black carbon and PM(2.5)
      were 3.9 MUg/m3 and 53.9 MUg/m3, respectively. The regression results showed that
      black carbon was significantly associated with total and cardiovascular
      mortality, but not with respiratory mortality. An inter-quartile range increase
      (2.7 MUg/m3) of black carbon corresponded to a 2.3% (95% confidence interval
      [CI]: 0.6-4.1), 3.2% (95% CI: 0.6-5.7), and 0.6% (95% CI: -4.5 to 5.7) increase
      in total, cardiovascular and respiratory mortality, respectively. When adjusted
      for PM(2.5), the effects of black carbon increased and remained statistically
      significant; in contrast, the associations of PM(2.5) with daily mortality
      decreased and became statistically insignificant after adjustment for black
      carbon. To our knowledge, this is the first study in China, or even in Asian
      developing countries, to report the acute effect of black carbon and PM(2.5) on
      daily mortality simultaneously. Our findings suggest that black carbon is a
      valuable additional air quality indicator to evaluate the health risks of ambient
      particles.

PMID- 22981951
TI  - Seminal fluid proteins differ in abundance between genetic lineages of honeybees.
AB  - Seminal fluid is transferred to the females' reproductive tract as part of the
      ejaculate and contains highly complex molecular machinery that is of central
      importance for male and female reproductive success. Interspecific studies
      suggest rapid evolutionary changes in the sequences of some seminal fluid
      proteins and also highlight the importance of specific seminal fluid proteins for
      sperm function and paternity success. Much less work has been conducted to study
      if variation in the steady-state abundance of seminal fluid proteins occurs
      within a species, which could provide a foundation for future selection to act
      upon. Here we used a unique breeding program of the honeybee Apis mellifera to
      provide evidence for quantified differences in seminal fluid protein abundances
      between three genetic lineages that have been bred for ~20 generations. We found
      the same subset of seminal fluid proteins to be present in all lines, but protein
      abundance or protein modification state varied significantly for 16% of the
      protein spots investigated. Protein spots with changed abundances were identified
      using mass spectrometry, with the abundance of a number documented from other
      species to be correlated with male fertility, reproductive success or immune
      competence. We conclude that significant alterations in the abundance or
      modification state of specific proteins in seminal fluid can be linked to
      different genotypes in honeybees.

PMID- 22981952
TI  - Lactobacillus reuteri DSM 17938 for the management of infantile colic in
      breastfed infants: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether administration of Lactobacillus reuteri (L
      reuteri) DSM 17938 is beneficial in breastfed infants with infantile colic. STUDY
      DESIGN: Eighty infants aged <5 months with infantile colic (defined as crying
      episodes lasting 3 or more hours per day and occurring at least 3 days per week
      within 7 days prior to enrollment), who were exclusively or predominantly (>50%)
      breastfed were randomly assigned to receive L reuteri DSM 17938 (10(8) colony
      forming units) (n = 40) or an identically appearing and tasting placebo (n = 40),
      both orally, in 5 drops, 1 time daily, for 21 days. The primary outcome measures
      were the treatment success, defined as the percentage of children achieving a
      reduction in the daily average crying time >= 50%, and the duration of crying
      (minutes per day) at 7, 14, 21, and 28 days after randomization. RESULTS: The
      rate of responders to treatment was significantly higher in the probiotic group
      compared with the placebo group at day 7 (P = .026), at day 14 (relative risk
      (RR) 4.3, 95% CI 2.3-8.7), at day 21 (RR 2.7, 95% CI 1.85-4.1), and at day 28 (RR
      2.5, 95% CI 1.8-3.75). In addition, throughout the study period, the median
      crying time was significantly reduced in the probiotic group compared with the
      control group. CONCLUSION: Exclusively or predominantly breastfed infants with
      infantile colic benefit from the administration of L reuteri DSM 17938 compared
      with placebo.

PMID- 22981949
TI  - The involvement of Reelin in neurodevelopmental disorders.
AB  - Reelin is a glycoprotein that serves important roles both during development
      (regulation of neuronal migration and brain lamination) and in adulthood
      (maintenance of synaptic function). A number of neuropsychiatric disorders
      including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's
      disease and lissencephaly share a common feature of abnormal Reelin expression in
      the brain. Altered Reelin expression has been hypothesized to impair neuronal
      connectivity and synaptic plasticity, leading ultimately to the cognitive
      deficits present in these disorders. The mechanisms for abnormal Reelin
      expression in some of these disorders are currently unknown although possible
      explanations include early developmental insults, mutations, hypermethylation of
      the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP
      underexpression and Reelin processing abnormalities. Increasing Reelin expression
      through pharmacological therapies may help ameliorate symptoms resulting from
      Reelin deficits. This article is part of the Special Issue entitled
      'Neurodevelopmental Disorders'.

PMID- 22981953
TI  - Preterm birth and airway inflammation in childhood.

PMID- 22981955
TI  - On the article titled "estimating species trees using approximate Bayesian
      computation" (Fan and Kubatko, Molecular Phylogenetics and Evolution 59:354-363).

PMID- 22981956
TI  - [Susceptibility genes, HLA and diabetic retinopathy in the Algerian population].
AB  - BACKGROUND: Diabetic retinopathy (DR) is the most frequent microvascular
      complication of type I diabetes (T1D). Some well-controlled type I diabetics may
      develop DR, while other poorly-controlled diabetics do not develop DR. This might
      be explained by certain susceptibility genes or protective genes. The purpose of
      our study is to search for any association between the HLA class I and II markers
      and DR in the Algerian population. PATIENTS AND METHODS: This study was carried
      out in 52 T1D subjects with and without DR compared to 140 healthy controls. HLA
      typing was performed using the "microlymphocytotoxicity" technique. RESULTS: The
      frequency of HLA-A29 and HLA-DR9 antigens is higher in T1D with DR compared to
      T1D without DR and to controls with frequencies of HLA-A29 (59.26% vs. 0%,
      OR=infinity, pc=4.6*10(-7)), (59.26% vs. 5.66%, OR=24.24, pc=7.6*10-10) and HLA
      DR9 (29.63% vs. 0%, OR=infinity, pc=1.310(-3)), (29.63% vs. 4.29%, OR=9.40,
      pc=7.010(-5)) respectively. However, the frequency of HLA-B49 antigen is
      significantly lower in T1D with DR than in T1D without DR (3.7% vs. 28%, OR=0.10,
      pc=8.8*10(-3)) and compared to controls (3.7% vs. 22.64%, OR=0.13, pc=0.011).
      CONCLUSION: HLA-A29 and HLA-DR9 antigens are probably markers of susceptibility
      for DR while HLA-B49 antigen is probably associated with a protective effect in
      the Algerian population.

PMID- 22981957
TI  - Excluded, not dismissed: enhancing benefit in clinical research.
AB  - Participation in clinical research projects may allow an opportunity for early
      detection of covert diseases and subclinical disorders in asymptomatic volunteers
      from study-specific screening process. Exclusion of a potential participant due
      to failure to meet inclusion criteria eliminates any possibility of potential for
      research related benefit, as may exist for those that are deemed eligible and
      allowed to proceed with participation in the specific research study. Although
      the institutional bodies overseeing conduct of clinical research strive to ensure
      an ongoing scrutiny and prioritization of participants' wellbeing, we perceive
      that these mechanisms fall short as regards the interests of those volunteers who
      are subsequently excluded from participation in clinical research of relevance.
      While provision of ancillary care to address health concerns that are unmasked
      during the screening process may be an optimal strategy, the likelihood of
      successfully implementing this latter concept in current times of fiscal
      constraints is slim to nonexistent. Through this submission, we hope to initiate
      a dialogue within the research community regarding whether the current paradigm
      of conduct of clinical research be modified to include some degree of
      consideration for the screened out. We herein propose that for those volunteering
      for disease/disorder specific clinical research, some added degree of benefit can
      be assured to the screened out population through the provision of targeted
      health education or counseling.

PMID- 22981958
TI  - The neuroethology of electrocommunication: how signal background influences
      sensory encoding and behaviour in Apteronotus leptorhynchus.
AB  - Weakly-electric fish are a well-established model system for neuroethological
      studies on communication and aggression. Sensory encoding of their electric
      communication signals, as well as behavioural responses to these signals, have
      been investigated in great detail under laboratory conditions. In the wave-type
      brown ghost knifefish, Apteronotus leptorhynchus, transient increases in the
      frequency of the generated electric field, called chirps, are particularly well
      studied, since they can be readily evoked by stimulating a fish with artificial
      signals mimicking conspecifics. When two fish interact, both their quasi
      sinusoidal electric fields (called electric organ discharge, EOD) superimpose,
      resulting in a beat, an amplitude modulation at the frequency difference between
      the two EODs. Although chirps themselves are highly stereotyped signals, the
      shape of the amplitude modulation resulting from a chirp superimposed on a beat
      background depends on a number of parameters, such as the beat frequency,
      modulation depth, and beat phase at which the chirp is emitted. Here we review
      the influence of these beat parameters on chirp encoding in the three primary
      stages of the electrosensory pathway: electroreceptor afferents, the hindbrain
      electrosensory lateral line lobe, and midbrain torus semicircularis. We then
      examine the role of these parameters, which represent specific features of
      various social contexts, on the behavioural responses of A. leptorhynchus. Some
      aspects of the behaviour may be explained by the coding properties of early
      sensory neurons to chirp stimuli. However, the complexity and diversity of
      behavioural responses to chirps in the context of different background parameters
      cannot be explained solely on the basis of the sensory responses and thus suggest
      that critical roles are played by higher processing stages. 

PMID- 22981959
TI  - Detection of buphedrone in biological and non-biological material--two case
      reports.
AB  - Buphedrone (2-(methylamino)-1-phenylbutan-1-one, alpha-methylamino-butyrophenone,
      MABP) is a positional isomer of mephedrone. In Poland, it was marketed in the
      second half of 2010 after the banning of mephedrone. Buphedrone is a stimulant
      that is snorted, smoked or taken orally. This substance was identified in 15
      products seized by law enforcement after August 2010 and analysed in the
      Institute of Forensic Research (IFR). Buphedrone was the sole psychoactive
      substance in only 5 products. It was mixed mainly with 4-MEC and MDPV. This paper
      presents two cases in which both biological and non-biological materials were
      delivered to the IFR for toxicological analysis. In the first case, a passenger
      car crashed into a truck. The car driver suffered severe injuries resulting in
      his death. During external inspection of the deceased the police discovered
      several packages containing a white powder. In the second case, a man was
      arrested for possession of illicit drugs. Analysis of powders was carried out
      using gas chromatography-mass spectrometry (GC-MS) and high-pressure liquid
      chromatography with diode array detection (HPLC-DAD). The purity of buphedrone
      found in powder samples was in the range of 58-68%. Analyses of blood were
      carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Buphedrone was found in the blood of the deceased at a concentration of 127 ng/mL
      and of the drug user/seller at 3 ng/mL.

PMID- 22981960
TI  - Bitemarks: distortion and covariation of the maxillary and mandibular dentition
      as impressed in human skin.
AB  - In bitemark analysis the extent of distortion of both maxillary and mandibular
      arches and how one affects the other has not been studied. A single dentition was
      used to create 49 bites on unembalmed cadavers. Landmarks were placed on digital
      images of the bitemarks and scanned images of the biting dentition. A sample of
      297 randomly acquired dental models was used for comparison purposes. Geometric
      morphometric techniques were utilized to statistically describe size and shape
      change, as well as the correlation between the two arches. Results indicate that
      the predominant distortion seen was in arch width, at 7-28 times as large as
      measurement error in the biting dentition and roughly 50% of the variation seen
      in the random population of dentitions. The correlation of arch width distortion
      between arches was very low (~0.03). However, the principal patterns of all shape
      variation did co-vary in the bitemarks produced by the maxillary and mandibular
      dentition, an effect indicating independence of size and shape distortion. In
      conclusion, bitemark analysis should be approached with caution when the
      principal difference between suspects is arch width.

PMID- 22981961
TI  - Post-mortem development of conjunctival petechiae following temporary prone
      position.
AB  - Conjunctival petechiae are an important diagnostic finding in external
      examination of forensic cases, being a sign of possible mechanical compression of
      the neck and jugular veins (e.g. choking, strangulation). Nevertheless, it is
      well known, that strong congestion of the conjunctival blood vessels might lead
      to the development of petechiae in the perimortal and early post mortem period,
      e.g. due to a head down position of the body. By now it remains unclear, whether
      a short term horizontal prone position of a body can lead to the development of
      conjunctival petechiae in the early post mortem period, a situation that might
      occur in everyday forensic casework. Therefore, we investigated the occurrence of
      conjunctival petechiae in 20 deceased at <12 h after death following a prone
      position of 2 h. Petechiae developed in 8 cases. Therefore, our results for the
      first time give evidence that conjunctival petechiae can be observed after a
      short-term horizontal prone position of a body in the early post mortem period,
      influencing the assessment of future forensic cases. Furthermore, statistical
      analysis revealed significant correlations with the examination method used to
      ectropionise the eyelids (forceps vs. cotton swab) and preceding resuscitation
      attempts. The latter observations should be considered in future research on the
      phenomenon.

PMID- 22981962
TI  - Soy isoflavones (daidzein & genistein) inhibit 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced cutaneous inflammation via modulation of COX-2 and NF
      kappaB in Swiss albino mice.
AB  - It is well established that aberrant production of inflammatory mediators has
      been associated with most the toxic manifestations and the genesis of different
      chronic diseases including cancer. The basic aim of the present study is to
      investigate the effects of soy isoflavones (SIF) on 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced cutaneous inflammatory responses and to explore the
      underlying molecular mechanisms. We have studied the protective effects of SIF
      against TPA induced oxidative stress, pro-inflammatory cytokines level,
      activation of NF-kappaB, expression of COX-2 and ki-67 in mouse skin. Animals
      were divided into five groups I-V (n=6). Groups II, III and IV received topical
      application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day, for 2
      days. Animals of the groups III and IV were pre-treated with SIF 1.0 MUg (D1) and
      2.0 MUg (D2) topically 30 min prior to each TPA administration, while groups I
      and V were given acetone (0.2 ml) and SIF (D2), respectively. We have found that
      SIF pretreatment significantly inhibited TPA induced oxidative stress,
      proinflammatory cytokines production and activation of NF-kappaB. SIF also
      inhibited the expression of COX-2 and ki-67. Histological findings further
      supported the protective effects of SIF against TPA-induced cutaneous damage.
      Thus, our results suggest that inhibitory effect of SIF on TPA-induced cutaneous
      inflammation includes inhibition of proinflammatory cytokines, attenuation of
      oxidative stress, activation of NF-kappaB and expression of COX-2.

PMID- 22981963
TI  - Treatment of hairy cell leukemia during pregnancy: are purine analogues and
      rituximab viable therapeutic options.

PMID- 22981964
TI  - Superior long-term outcome of patients with early transformation of non-Hodgkin
      lymphoma undergoing stem cell transplantation.
AB  - In this study, we discuss the results of patients with transformed lymphoma (TL)
      undergoing stem cell transplantation (SCT). Because of the paucity of literature
      on the treatment of TL, deciding on the optimal evidence-based treatment is a
      challenge. Herein, our results indicate that patients with early transformation
      may benefit the most from SCT. BACKGROUND: Transformed non-Hodgkin's lymphoma
      arising from follicular lymphoma (TL) carries a poor prognosis with a median
      survival time after transformation reported to be approximately 1 year. PATIENTS
      AND METHODS: Fifty-one consecutive patients with TL received SCT between January
      2000 and December 2010 (autologous SCT, n = 44, allogeneic SCT, n = 7). RESULTS:
      Thirty-six (70.5%) patients had an early transformation, defined as histologic
      evidence of transformation at the time of initial diagnosis or transformation
      within 1 year of follicular lymphoma. Fifteen patients had early stage disease
      (29%) and 36 (71%) had advanced stage disease on presentation. At the time of
      analysis, 37 patients were alive with an estimated 5-year overall survival (OS)
      and event free survival (EFS) of 61.8% and 45%, respectively. OS and EFS were not
      significantly different between types of transplant procedure. The major cause of
      transplant failure was disease recurrence, with estimated 2-year relapse rate of
      37.4%. Importantly, early transformation was independently associated with
      improved OS (hazard ratio [HR] 3.29; P = .028) and EFS (HR 2.49; P = .029).
      CONCLUSION: Our results indicate that an aggressive transplant approach should be
      considered first in patients with TL and emphasize the need to incorporate novel
      strategies (eg, immunomodulation) early post-SCT to prevent relapses as disease
      recurrence remains the major cause of failure in heavily pretreated patients.

PMID- 22981965
TI  - Solid, low-attenuation splenic lesions on computed tomography in patients with
      indolent lymphoma often signal transformation: a series of ten patients.

PMID- 22981966
TI  - Assessment of vulnerability measures and their effect on survival in a real-life
      population of multiple myeloma patients registered at Marche Region Multiple
      Myeloma Registry.
AB  - Multiple myeloma (MM) therapy should be tailored according to patient
      characteristics although we do not know which ones to use. By studying the
      characteristics of 266 real-life patients, we found performance status (PS) and
      Charlson Comorbidity Index (CCI) as factors affecting survival of MM patients
      regardless of their disease characteristics. This study might help to select
      patients for tailoring therapy in clinical practice. BACKGROUND: Multiple myeloma
      is a typical disease of the elderly but how many and which patients can be
      considered 'vulnerable' and how this may affect patient outcome remain unsolved
      issues. PATIENTS AND METHODS: Data from 266 symptomatic MM patients registered at
      Marche MM registry from 2007 to 2010 were evaluated retrospectively.
      Vulnerability was defined as age > 75 years, PS (World Health Organization) >= 2,
      renal insufficiency (RI), bone fracture, cytopenias, and CCI score >= 1. Kaplan
      Meier method and Cox regression were used to assess survival and associated
      factors. A vulnerability score (VS) incorporating significant vulnerability
      features was pursued to predict survival. RESULTS: Thirty-eight percent of
      patients were older than 75 years, 39% had PS = 2-4, 35% had at least 2
      cytopenias, 40% had bone fracture, 14% RI, and 51% had CCI score >= 1. Cox
      regression selected international staging system (ISS) = III (hazard ratio [HR] =
      1.6; P = .033), PS = 2-4 (HR = 2.5; P = .007), and CCI = 1-3 (HR = 2.1; P = .028)
      as factors associated with a worse overall survival. A VS including PS and CCI
      predicted median survival of 27 months in the 63 patients having a VS = 2 (both
      PS = 2-4 and CCI = 1-3) versus not reached (NR) in the 203 patients with VS = 0-1
      (HR = 4.0; P < .0001). In younger patients multivariate analysis selected ISS =
      III (HR = 5.2; P = .006) and VS = 2 (HR = 5.5; P = .024) as factors associated
      with shorter survival whereas only VS = 2 (HR = 3.5; P = .002) affected worse
      survival in elderly. CONCLUSION: Such VS proved to be a powerful prognostic
      factor for survival of MM patients and it might be useful to identify true
      vulnerable patients regardless of age.

PMID- 22981967
TI  - Biochemical analysis of the epitope specificities of anti-C1q autoantibodies
      accompanying human lupus nephritis reveals them as a dynamic population in the
      course of the disease.
AB  - We analyzed the epitope specificities of the polyclonal anti-C1q antibodies,
      present in human LN sera, searching to deduce the structural characteristics of
      C1q associated with its transition to an autoantigen. We screened 78 serum
      samples from LN patients distributed in three clinical groups - non-active,
      moderately active and severely active. We found three classes of C1q
      autoepitopes: (a) neo-epitopes, exposed upon immobilization due to conformational
      changes; (b) epitopes formed by sequences that are brought together by the
      conformation of the whole molecule; (c) cryptic epitopes that become exposed only
      after fragmentation of C1q. The latter suggest that the immunogen involved in the
      initiation of anti-C1q autoantibodies might be an extrinsic molecule that shares
      some degree of structural similarity to C1q. None of the tested epitope
      specificities was associated with active LN. We found a prevalence of anti-gC1q
      antibodies among the non-active LN patients suggesting that they might be the
      fraction of the polyclonal anti-C1q, preceding the initiation of autoimmunity to
      C1q, or alternatively, preceding LN flare.

PMID- 22981968
TI  - Structure and function of ionocytes in the freshwater fish gill.
AB  - Freshwater fishes lose ions to the external medium owing to the steep
      concentration gradients between the body fluids and the water. To maintain
      homeostasis, they use ionocytes to actively extract Na(+), Cl(-), and Ca(2+) from
      the dilute external medium and excrete acidic (H(+)) or basic (HCO(3)(-))
      equivalents by specialized cells termed ionocytes that are responsible for
      transport of ions. Freshwater fishes have evolved diverse approaches to solving
      these similar ionic and acid-base problems. In the few well-studied species,
      there are clearly different patterns in the physiology and morphology for
      ionocytes in the gill. In this review, we describe the varying nomenclature of
      ionocytes that have been used in the past 80 years to allow direct comparison of
      ionocytes and their common functions in different species. We focus on the recent
      advancement in our understanding of the molecular mechanisms of ion and acid-base
      regulation as represented by ionocyte subtypes found in rainbow trout, killifish,
      tilapia and zebrafish gill.

PMID- 22981969
TI  - A single test for the determination of parameters of the speed-time relationship
      for running.
AB  - A validated expeditious method is needed to determine critical speed (CS) and the
      finite distance that can be covered above CS (D'). We tested the hypothesis that
      a single all-out 3-min running test would accurately determine CS and D'. Seven
      healthy subjects completed three constant-speed runs on a treadmill for the
      determination of CS and D', as well as an all-out 3-min test on a track for the
      determination of end-test speed (ES) and the distance above end-test speed (DES).
      ES (13.4 +/- 2.8 km h(-1)) was not significantly different from the speed-1/time
      model CS (13.3 +/- 2.8 km h(-1)). While DES (141 +/- 34 m) was not significantly
      different from D' (204 +/- 103 m), it underestimated D' in 5 of 7 subjects. Thus,
      the speed-1/time model CS can be accurately determined using a single 3-min test,
      while caution should be used in relating DES to D'.

PMID- 22981970
TI  - Organ-sparing Intensity-modulated radiotherapy for anal cancer using the ACTII
      schedule: a comparison of conventional and intensity-modulated radiotherapy
      plans.
AB  - AIMS: Conventional external beam radiotherapy for anal cancer is associated with
      a high rate of treatment-related morbidity. The purpose of this retrospective
      study was to compare the dosimetric advantages of three intensity-modulated
      radiotherapy (IMRT) plans with the conventional plan with regards to organs at
      risk avoidance delivering the ACTII schedule of 50.4 Gy in 1.8 Gy/fraction: 17
      fractions for phase 1 and 11 fractions for phase 2. MATERIALS AND METHODS: Ten
      anal cancer patients (T1-3 N0-3) treated with the conventional plan using four
      fields and conformal boost were identified. The phase 1 planning target volume
      (PTV) included tumour, anal canal and inguinal, peri-rectal and internal/external
      iliac nodes. Phase 2 included identifiable disease only. Three step-and-shoot
      IMRT plans were generated: IMRT1: phase 1 inverse-planned IMRT with two- to four
      field conformal phase 2; IMRT2: both phase 1 and phase 2 inverse-planned IMRT;
      IMRT3: phase 1 IMRT and phase 2 forward-planned IMRT. All IMRT plans were then
      compared against the conventional plan on PTV coverage, small bowel, genitalia,
      femoral heads, bladder and healthy tissue dose volume information. RESULTS: While
      achieving similar PTV coverage compared with the conventional plan, significant
      dose reductions were observed for IMRT plans in external genitalia, small bowel
      and healthy tissue. Reductions were also observed in the femoral heads and
      bladder. CONCLUSIONS: IMRT significantly reduces the dose to organs at risk while
      maintaining excellent PTV coverage in anal cancer radiotherapy.

PMID- 22981971
TI  - A single exposure to bisphenol A alters the levels of important neuroproteins in
      adult male and female mice.
AB  - Bisphenol A (BPA) is widely used in polymer products in food and beverage
      containers, baby bottles, dental sealants and fillings, adhesives, protective
      coatings, flame retardants, water supply pipes, and compact discs, and is found
      in the environment and in placental tissue, fetuses and breast milk. We have
      recently reported that a single neonatal exposure to bisphenol A can induce
      persistent aberrations in spontaneous behavior, in a dose-dependent manner, and
      affect the adult response to the cholinergic agent nicotine. Furthermore, other
      recent reports indicate that pre- and perinatal exposure to bisphenol A can
      induce neurotoxic effects. The present study indicates that a single neonatal
      exposure to bisphenol A, on postnatal day 10, during the peak of the brain growth
      spurt, can alter the adult levels of proteins important for normal brain
      development (CaMKII and synaptophysin). These alterations are induced in both
      male and female mice and effects are seen in both hippocampus and cerebral
      cortex. These results further support our recent study showing that neonatal
      exposure to bisphenol A can act as a developmental neurotoxicant and the effects
      are similar to effects seen after a single postnatal exposure to other POPs, such
      as PBDEs, PCBs and PFCs.

PMID- 22981973
TI  - [Prevention of mother-to-child transmission of toxoplasmosis: perspectives].
AB  - In France, screening for toxoplasmosis is mandatory during pregnancy, whereas it
      is not performed in most other countries. The rationale for prenatal screening is
      to allow for several levels of intervention: primary prevention by health
      education; in case of seroconversion, prophylactic therapy; prenatal diagnosis
      using amniocentesis; the possibility of termination of pregnancy (TOP) in case of
      severe cerebral lesions at ultrasound; in most cases of fetal infection,
      antiparasitic therapy prenatally as well as postnatally. The French Health
      Authority (Haute Autorite de sante [HAS]) called into question the screening
      policy, but maintained it for 5 years pending randomized clinical trials. Recent
      data is available to answer some of the questions, but not the place of prenatal
      therapy. The sensitivity of prenatal diagnosis has progressed, while the place of
      TOP has decreased. The incidence of toxoplasmosis in the French population has
      fallen. Some studies have shown evidence in favor of prenatal therapy for
      infected fetuses. However, studies of prophylactic therapy are disappointing.
      These studies are purely observational and concern mostly spiramycine. For the
      first time, a multicenter randomized clinical trial of prevention of mother-to
      child transmission of Toxoplasma gondii is underway (the TOXOGEST study). The HAS
      guidelines are that any suspected toxoplasmosis seroconversion should be
      confirmed in a reference laboratory, and that patients should be referred to
      expert centers without delay. It is not recommeded to start therapy before such
      expert consultation. The reference centers should provide counseling and access
      to prenatal diagnosis and therapy options.

PMID- 22981972
TI  - Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in essential tremor
      cases in Spain.
AB  - BACKGROUND: Environmental correlates for essential tremor (ET) are largely
      unexplored. The search for such environmental factors has involved the study of a
      number of neurotoxins. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent
      tremor-producing toxin. In two prior case-control studies in New York, we
      demonstrated that blood harmane concentration was elevated in ET patients vs.
      controls, and especially in familial ET cases. These findings, however, have been
      derived from a study of cases ascertained through a single tertiary referral
      center in New York. OBJECTIVE: Our objective was to determine whether blood
      harmane concentrations are elevated in familial and sporadic ET cases,
      ascertained from central Spain, compared to controls without ET. METHODS: Blood
      harmane concentrations were quantified by a well-established high performance
      liquid chromatography method. RESULTS: The median harmane concentrations were:
      2.09 g(-10)/ml (138 controls), 2.41 g(-10)/ml (68 sporadic ET), and 2.90 g(
      10)/ml (62 familial ET). In an unadjusted logistic regression analysis, log blood
      harmane concentration was not significantly associated with diagnosis (familial
      ET vs. control): odds ratio=1.56, p=0.26. In a logistic regression analysis that
      adjusted for evaluation start time, which was an important confounding variable,
      the odds ratio increased to 2.35, p=0.049. CONCLUSIONS: Blood harmane levels were
      slightly elevated in a group of familial ET cases compared to a group of controls
      in Spain. These data seem to further extend our observations from New York to a
      second cohort of ET cases in Spain. This neurotoxin continues to be a source of
      interest for future confirmatory research.

PMID- 22981974
TI  - [Breast cancers and gene expression signatures: here and now].

PMID- 22981975
TI  - [Predictive factors for fetal tolerance to cordocentesis: a monocentric
      retrospective study].
AB  - OBJECTIVES: Indications for fetal blood sampling (FBS) are getting more limited.
      In this context, we aimed to evaluate fetal loss and morbidity associated with
      FBS and to precise the predictive parameters for fetal complications. More than a
      retrospective evaluation of our practices, the final end point of our study was
      to better inform the patients coming to our centre. PATIENTS AND METHODS:
      Retrospective monocentric cohort (Canadian Task Force classification II-2) of the
      99 FBS performed between April 2004 and June 2010 on 80 fetuses, after excluding
      the procedures done for termination of pregnancy. The main clinical outcome was a
      composite outcome criteria for fetal tolerance including cesarean section for
      abnormal non stress test within the 24 hours, or any event responsible of a
      modified obstetrical management during the 14 day following FBS. RESULTS: Mean
      maternal age at FBS was 30 years +/- 5.13 SD and parity was 2.49 +/- 1.38 SD. FBS
      was performed by an experienced operator in 86.5% of cases (CI 95%, 78-92.6);
      with a single insertion in 83.3% of circumstances (CI 95%, 74.4-90.2). The mean
      duration was 11 min +/- 6.37 SD. The total rate of intrauterine death, in our
      series, was 7.1% (CI 95%, 2.9-14), including all reported fetal demise within the
      14 days after FBS, whatever the relation with the procedure. Our study
      demonstrated a 9.1% occurrence of post-FBS altered CTG fetal testing (CI 95%, 4.2
      16.6), half of it with spontaneous resolution. The rate of severe complications
      (main clinical outcome) was 11.1% (CI 95%, 5.7-19) including one fetal death
      liable to FBS and 10 emergency caesarean sections: 5.1% for fetal bradycardia (CI
      95%, 1.7-11.4), 2% for placental abruption (CI 95%, 0.2-7.1), 2% for premature
      preterm rupture of membranes (CI 95%, 0.2-7.1) and 1% for significative umbilical
      cord bleeding (CI 95%, 0-5.5). Univariate factor analysis highlights 4 parameters
      for impaired fetal tolerance; a prolonged procedure, presence of low fetal
      platelets (<30.10(9)/L); and FBS performed for fetal anaemia during Parvovirus
      B19 infection or allo-immune thrombocytopenia. DISCUSSION AND CONCLUSION: FBS
      remains a tricky procedure with a substantial risk of fetal loss or complications
      especially when performed on high-risk foetuses. The length of the procedure
      should be shortened as much as possible (trained operator, postponed procedure
      when all favourable condition are not available). Fetal thrombocytopenia is a
      meaningful risk factor encouraging carefulness when exploring allo-immune fetal
      thrombocytopenia.

PMID- 22981976
TI  - Effect of the exposure to methyl-beta-cyclodextrin prior to chilling or
      vitrification on the viability of bovine immature oocytes.
AB  - The present study aimed to evaluate the effect of methyl-beta-cyclodextrin
      (MbetaCD) as a cholesterol loader to change oocyte plasma membrane and increase
      its tolerance toward cryopreservation. The first and second experiments were
      conducted to investigate if MbetaCD could improve nuclear and cytoplasmic
      maturation after oocyte exposure to cold stress for 10 or 30 min, respectively.
      No differences (P>0.05) in either experiment in the metaphase II (MII) rate of
      oocytes exposed to MbetaCD and cold stress; but these oocytes presented lower
      maturation rates than control groups. In the second experiment, a lower
      percentage of oocytes showed degenerated chromatin (P<0.05) after exposure to
      2mg/mL of MbetaCD compared to the group exposed to 0mg/mL. However, no
      differences among treatments were observed in cytoplasmic maturation. Groups
      exposed to cold stress demonstrated a lower (P<0.05) capacity for embryonic
      development compared to the control groups. In the third experiment immature
      oocytes were exposed to MbetaCD and then, vitrified (cryotop). After warming, we
      observed that the ability to reach MII and chromatin degeneration were altered
      (P<0.05) by MbetaCD. The blastocysts rate (P<0.05) on D7 was higher in the 2
      mg/mL MbetaCD group, but an identical finding was not observed on D8 (P>0.05).
      Chromatin degeneration was higher in the vitrification groups. We conclude that
      MbetaCD improved nuclear maturation by reducing oocyte degeneration after cold
      stress or vitrification; however, more studies are required to clarify the
      usefulness of MbetaCD use in oocyte cryopreservation.

PMID- 22981977
TI  - The immunosuppressant cyclosporin A inhibits recurrent seizures in an
      experimental model of temporal lobe epilepsy.
AB  - The immunosuppressant, cyclosporin A (CsA), is neuroprotective following brain
      injury. Previous studies suggest that CsA treatment ameliorates seizure severity
      during status epilepticus (SE) or cell death following SE. The antiepileptic
      effects of CsA on recurrent seizures, however, have not been investigated. In the
      present study, the effects of CsA on spontaneous recurrent seizures (SRSs) in a
      kainate (KA)-induced mouse model of mesial temporal lobe epilepsy (TLE) were
      examined. Moreover, the effects of CsA on epileptiform activity in a 4
      aminopyridine (4-AP)-induced in vitro seizure model were investigated. A mesial
      TLE mouse model was generated with a unilateral intrahippocampal injection of KA.
      SRSs were determined in the ipsilateral hippocampal CA1 region with a long-term
      video-EEG. CsA was systemically administrated to the epileptic mice exhibiting a
      stable occurrence of SRSs. A 1-mg/kg dose of CsA did not have any effect on SRSs
      in the epileptic mice. However, a 5-mg/kg dose of CsA significantly reduced the
      number of SRSs and decreased the severity of the seizures in the epileptic mice.
      Additionally, CsA treatment inhibited spontaneous burst discharges in 4-AP
      treated hippocampal slices. The results of the present study demonstrate that CsA
      inhibits recurrent seizures in a mouse model of mesial TLE and suggest that CsA
      may afford both neuroprotection against SE and antiepileptic effects during the
      chronic period of epilepsy.

PMID- 22981978
TI  - Neuropathic pain and reactive gliosis are reversed by dialdehydic compound in
      neuropathic pain rat models.
AB  - The role of the purinergic system in the modulation of pain mechanisms suggests
      that it might be promising target for treating neuropathic pain. In this study we
      evaluated the effects of two different dialdehydic compounds: a modified stable
      adenosine (2-[1-(6-amminopurin-9-il)-2-osso-etossi]prop-2-enale, named MED1101),
      and oxidized ATP (Ox-ATP), in two different neuropathic pain rat models: the
      sciatic spared nerve injury (SNI) and paclitaxel evoked painful peripheral
      neuropathy (pPPN). Neuropathic animals were divided in groups as follows: (a)
      treated with intraperitoneal (i.p.) MED1101 or Ox-ATP for 21 days; (b) receiving
      vehicle (VEH) and (c) control (CTR) rats. The allodynic and hyperalgesic behavior
      was investigated by Von Frey filament test and thermal Plantar test,
      respectively. We evaluated by immunocytochemistry the astrocytic (GFAP) and
      microglial (Iba1) response on lumbar spinal cord sections. In either experimental
      models and using either substances, treated animals showed reduced allodynia and
      thermal hyperalgesia paralleled by a significant reduction of glial reaction in
      the spinal cord. These data prompt to hypothesize a potential role of dialdehydes
      as analgesic agent in chronic neuropathic pain and a possible role as anti
      gliotic molecules.

PMID- 22981979
TI  - An indirect role for oncomir-519b in the expression of truncated neurokinin-1 in
      breast cancer cells.
AB  - Neurokinin 1 (NK1) encodes full-length (NK1-FL) and truncated (NK1-Tr) receptors,
      with distinct 3' UTR. NK1-Tr exerts oncogenic functions and is increased in
      breast cancer (BC). Enhanced transcription of NK1 resulted in higher level of NK1
      Tr. The 3' UTR of these two transcripts are distinct with NK1-Tr terminating at a
      premature stop codon. NK1-Tr mRNA gained an advantage over NK1-FL with regards to
      translation. This is due to the ability of miR519B to interact with sequences
      within the 3' UTR of NK1-FL, but not NK1-Tr since the corresponding region is
      omitted. MiR519b suppressed the translation of NK1-FL in T47D and MDA-MB-231
      resulting in increased NK1-Tr protein. Cytokines can induce the transcription of
      NK1. However, our studies indicated that translation appeared to be independent
      of cytokine production by the BC cells (BCCs). This suggested that transcription
      and translation of NK1 might be independent. The findings were validated in vivo.
      MiR-519b suppressed the growth of MDA-MB-231 in 7/10 nude BALB/c. In total,
      increased NK1-Tr in BCCs is due to enhanced transcription and suppressed
      translation of NK1-FL by miR-519b to reduced tumor growth. In summary, we report
      on miRNA as a method to further regulate the expression of a spiced variant to
      promote oncogenesis. In addition, the findings have implications for therapy with
      NK1 antagonists. The oncogenic effect of NK1-Tr must be considered to improve the
      efficacy of current drugs to NK1.

PMID- 22981980
TI  - Design and heterologous expression of dengue virus envelope protein (E) peptides
      and their use for serological diagnosis.
AB  - Viruses belonging to the Flaviviridae family are found and distributed in most of
      the tropical and sub-tropical regions of the world. The genus has more than 56
      members, most of which cause clinical symptoms in humans. The clinical diagnosis
      of dengue requires laboratory confirmation because of the similarity of symptoms
      with a series of other acute fevers and the primary use antibodies or antigens
      for detection. In this work, peptides E(1) and E(2) of the envelope protein (E)
      of the dengue virus were mapped using bioinformatics methods. These peptides were
      then expressed in a prokaryotic system and purified. An indirect ELISA for
      antibodies IgG and IgM from laboratory samples previously characterised was then
      used with the peptides to detect anti-dengue antibodies. For IgG using the
      peptide E(1), the sensitivity of the indirect ELISA was 88.3% and the specificity
      was 56%; using the peptide E(2), the sensitivity was 90% and the specificity was
      59%; and using a combination of both peptides, the sensitivity was 93.3% and the
      specificity was 78%. For IgM using the peptide E(1), the sensitivity was 88% and
      the specificity was 66%; using the peptide E(2), the sensitivity was 88% and the
      specificity was 69%; and when used in combination, the peptides E(1)/E(2)
      demonstrated a sensitivity of 90% and a specificity of 86%. These results
      indicate that the use of the E(1) and E(2) peptides of the E protein are an
      alternative for serological diagnosis of dengue fever.

PMID- 22981981
TI  - Indirect-blocking ELISA for detecting antibodies against glycoprotein B (gB) of
      porcine cytomegalovirus (PCMV).
AB  - The major epitope region of the glycoprotein B (gB) gene of the porcine
      cytomegalovirus (PCMV), with a length of 270 bp, was cloned and expressed in
      Escherichia coli Rosetta (DE3). The major gB epitope was detected using an agar
      gel precipitation and Western blot analysis with the polyclonal antibodies
      specific for the major epitope. An indirect-blocking enzyme-linked immunosorbent
      assay (ELISA) was developed using the expressed major gB epitope as a coating
      antigen for the detection of PCMV antibodies. The results of the tests show that
      the indirect-blocking ELISA has 98% specificity and 97.8% sensitivity. No cross
      reactions were observed between the major gB epitope and the antibodies against
      other virus, which indicates that the gB epitope is specific for PCMV antibodies.
      The indirect-blocking ELISA is a highly specific, sensitive method for detecting
      anti-PCMV gB antibodies.

PMID- 22981982
TI  - Adenovirus-vectored type Asia1 foot-and-mouth disease virus (FMDV) capsid
      proteins as a vehicle to display a conserved, neutralising epitope of type O
      FMDV.
AB  - The objective of this study was to explore the immunogenicity of an adenovirus
      construction expressing a type O foot and mouth disease virus neutralising
      epitope (8E8) in the context of heterologous capsid proteins. Adenoviruses
      expressing four chimeric type Asia1 FMDV capsid proteins were constructed by
      inserting the type O FMDV 8E8 epitope into the G-H loop from the type Asia1 VP1
      at amino acid residues 139/140, 150/151, 134/140 or at both 139/140 and 150/151.
      These recombinant proteins were recognised by antibodies against the type O 8E8
      epitope and type Asia1 FMDV. When inoculated in mice, all of the recombinant
      chimeric capsid proteins for each single epitope insertion induced the production
      of anti-type O FMDV neutralising antibodies. The recombinant chimeric capsid
      proteins with a foreign insertion at position 139/140 or 150/151 induced high
      levels of anti-type Asia1 FMDV neutralising antibodies as the recombinant type
      Asia1 capsid proteins without any foreign epitope, suggesting that the foreign
      insertion did not affect the immunogenicity of the type Asia1 FMDV capsid
      proteins. This study suggests that a foreign epitope displayed on the surface of
      the FMDV capsid proteins could induce an epitope-specific response. Therefore,
      the adenovirus-vectored FMDV capsid proteins could be used as a vehicle for the
      development of an epitope-based vaccine.

PMID- 22981983
TI  - Evaluation of the Tetracore Orthopox BioThreat(r) antigen detection assay using
      laboratory grown orthopoxviruses and rash illness clinical specimens.
AB  - The commercially available Orthopox BioThreat(r) Alert assay for orthopoxvirus
      (OPV) detection is piloted. This antibody-based lateral-flow assay labels and
      captures OPV viral agents to detect their presence. Serial dilutions of cultured
      Vaccinia virus (VACV) and Monkeypox virus (MPXV) were used to evaluate the
      sensitivity of the Tetracore assay by visual and quantitative determinations;
      specificity was assessed using a small but diverse set of diagnostically relevant
      blinded samples from viral lesions submitted for routine OPV diagnostic testing.
      The BioThreat(r) Alert assay reproducibly detected samples at concentrations of
      10(7)pfu/ml for VACV and MPXV and positively identified samples containing
      10(6)pfu/ml in 4 of 7 independent experiments. The assay correctly identified 9
      of 11 OPV clinical samples and had only one false positive when testing 11 non
      OPV samples. Results suggest applicability for use of the BioThreat(r) Alert
      assay as a rapid screening assay and point of care diagnosis for suspect human
      monkeypox cases.

PMID- 22981984
TI  - Molecular cloning and characterization of three cDNAs encoding allatostatin-like
      neurosecretory peptides from Pandalopsis japonica.
AB  - Three cDNAs encoding allatostatin-like peptides (two myoinhibitory peptides; Paj
      MIPI and Paj-MIPII, and one C-type AST; Paj-ASTC) were identified from
      Pandalopsis japonica through a combination of bioinformatic analysis and PCR
      based gene cloning strategy. Paj-MIPI and Paj-MIPII encoded proteins with 189 and
      117 amino acid residues, respectively, and a total of 10 mature peptides are
      putatively produced from the two MIP cDNAs (seven from Paj-MIPI and three from
      Paj-MIPII). Among the MIPs from various arthropods, their size and organization
      varied and it was unable to establish the monophyletic evolutionary relationship,
      which is mainly due to difference in the number and location of the mature
      peptide W(X(6))W motif of each MIP gene. Based on the sequence similarity of six
      residues flanked by two conserved tryptophan (W) residues, crustacean MIPs could
      be further classified into at least four groups. Paj-ASTC cDNA (648bp) encoded a
      protein with 143 amino acid residues. The prepropeptide of Paj-ASTC showed
      conserved C-type AST characteristics including a signal sequence, two dibasic
      cleavage sites, and a mature peptide sequence with two cysteine residues at the
      7th and 14th positions, creating a disulfide bridge. Based on the sequence
      similarity in the mature peptides, the ASTCs in arthropods could be further
      classified into two subgroups, AVSCF-ASTC and PISCF-ASTC. Phylogenetic and
      sequence similarity analysis showed that Paj-ASTC belonged to the PISCF-ASTC
      subgroup. Expression studies revealed that AST-like peptides from P. japonica
      were mainly expressed in neuronal tissues, and the expression of Paj-ASTC was
      also detected in the intestine. Eyestalk ablation (ESA) altered the mRNA
      expression levels of both Paj-MIPs and Paj-ASTC, suggesting that factors from the
      sinus gland/X organ complex had a transient effect on AST-like peptide
      transcription. Correlation analysis of three allatostatin-like peptides revealed
      a strong positive correlation in brain tissues, suggesting that transcriptional
      regulation of three allatostatin-like peptides from P. japonica is influenced by
      the similar physiological condition.

PMID- 22981985
TI  - Mechanistic basis for the effects of process parameters on quality attributes in
      high shear wet granulation.
AB  - Three model compounds were used to study the effect of process parameters on in
      process critical material attributes and a final product critical quality
      attribute. The effect of four process parameters was evaluated using design of
      experiment approach. Batches were characterized for particle size distribution,
      density (porosity), flow, compaction, and dissolution rate. The mechanisms of the
      effect of process parameters on primary granule properties (size and density)
      were proposed. Water amount showed significant effect on granule size and
      density. The effect of impeller speed was dependent on the granule mechanical
      properties and efficiency of liquid distribution in the granulator. Blend density
      was found to increase rapidly during wet massing. Liquid addition rate was the
      least consequential factor and showed minimal impact on granule density and
      growth. Correlations of primary properties with granulation bulk powder
      properties (compaction and flow) and tablet dissolution were also identified. The
      effects of the process parameters on the bulk powder properties and tablet
      dissolution were consistent with their proposed link to primary granule
      properties. Understanding the impact of primary granule properties on bulk powder
      properties and final product critical quality attributes provides the basis for
      modulating granulation parameters in order to optimize product performance.

PMID- 22981986
TI  - Preliminary validation of varicella zoster virus thymidine kinase as a novel
      reporter gene for PET.
AB  - INTRODUCTION: Imaging of gene expression with positron emission tomography (PET)
      has emerged as a powerful tool for biomedical research during the last decade.
      The prototypical herpes simplex virus type 1 thymidine kinase (HSV1-TK) PET
      reporter gene (PRG) is widely used and many other PRGs have also been validated.
      We investigated varicella zoster virus thymidine kinase (VZV-tk) as new PRG with
      radiolabeled bicyclic nucleoside analogues (BCNAs) as PET tracers. METHODS: The
      uptake and washout of four different radiolabeled BCNAs was evaluated in cells
      expressing VZV-tk after lentiviral vector (LV) transduction and in control cells.
      Metabolism of the tracers was assayed by high pressure liquid chromatography
      (HPLC). Mice bearing VZV-TK expressing xenografts were imaged with PET. RESULTS:
      High uptake in VZV-tk expressing cells was seen for 3 of the 4 tracers tested.
      The uptake of the tracers could be blocked by the presence of excess thymidine in
      the incubation solution. Cellular retention was variable, with one tracer showing
      an acceptable half-life of ~1 hour. The amount of intracellular tracer correlated
      with the titer of LV used to transduce the cells. VZV-TK dependent conversion
      into metabolites was shown by HPLC. No specific accumulation was observed in
      cells expressing a fusion protein containing an HSV1-TK moiety. VZV-tk expression
      in xenografts resulted in a 60% increase in uptake in vivo as measured with PET.
      CONCLUSIONS: We have validated the combination of VZV-tk and radiolabeled BCNAs
      as new PRG/PRP system. Further optimization of the PRPs and the PRG are warranted
      to increase the signal.

PMID- 22981987
TI  - Synthesis and preclinical evaluation of the radiolabeled P-glycoprotein inhibitor
      [(11)C]MC113.
AB  - OBJECTIVES: With the aim to develop a PET tracer to visualize P-glycoprotein
      (Pgp) expression levels in different organs, the Pgp inhibitor MC113 was labeled
      with (11)C and evaluated using small-animal PET. METHODS: [(11)C]MC113 was
      synthesized by reaction of O-desmethyl MC113 with [(11)C]methyl triflate. Small
      animal PET was performed with [(11)C]MC113 in FVB wild-type and Mdr1a/b((-/-))
      mice (n=3 per group) and in a mouse model of high (EMT6Ar1.0) and low (EMT6) Pgp
      expressing tumor grafts (n=5). In the tumor model, PET scans were performed
      before and after administration of the reference Pgp inhibitor tariquidar
      (15mg/kg). RESULTS: Brain uptake of [(11)C]MC113, expressed as area under the
      time-activity curve from time 0 to 60min (AUC(0-60)), was moderately but not
      significantly increased in Mdr1a/b((-/-)) compared with wild-type mice (mean+/-SD
      AUC(0-60), Mdr1a/b((-/-)): 88+/-7min, wild-type: 62+/-6min, P=0.100, Mann Whitney
      test). In the tumor model, AUC(0-60) values were not significantly different
      between EMT6Ar1.0 and EMT6 tumors. Neither in brain nor in tumors was activity
      concentration significantly changed in response to tariquidar administration.
      Half-maximum effect concentrations (IC(50)) for inhibition of Pgp-mediated
      rhodamine 123 efflux from CCRFvcr1000 cells were 375+/-60nM for MC113 versus
      8.5+/-2.5nM for tariquidar. CONCLUSION: [(11)C]MC113 showed higher brain uptake
      in mice than previously described Pgp PET tracers, suggesting that [(11)C]MC113
      was only to a low extent effluxed by Pgp. However, [(11)C]MC113 was found
      unsuitable to visualize Pgp expression levels presumably due to insufficiently
      high Pgp binding affinity of MC113 in relation to Pgp densities in brain and
      tumors.

PMID- 22981988
TI  - The BAR domain protein Arfaptin-1 controls secretory granule biogenesis at the
      trans-Golgi network.
AB  - BAR domains can prevent membrane fission through their ability to shield necks of
      budding vesicles from fission-inducing factors. However, the physiological role
      of this inhibitory function and its regulation is unknown. Here we identify a
      checkpoint involving the BAR-domain-containing protein Arfaptin-1 that controls
      biogenesis of secretory granules at the trans-Golgi network (TGN). We demonstrate
      that protein kinase D (PKD) phosphorylates Arfaptin-1 at serine 132, which
      disrupts the ability of Arfaptin-1 to inhibit the activity of ADP ribosylation
      factor, an important component of the vesicle scission machinery. The
      physiological significance of this regulatory mechanism is evidenced by loss of
      glucose-stimulated insulin secretion due to granule scission defects in
      pancreatic beta cells expressing nonphosphorylatable Arfaptin-1. Accordingly,
      depletion of Arfaptin-1 leads to the generation of small nonfunctional secretory
      granules. Hence, PKD-mediated Arfaptin-1 phosphorylation is necessary to ensure
      biogenesis of functional transport carriers at the TGN in regulated secretion.

PMID- 22981989
TI  - A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia.
AB  - Vertebrate Hedgehog (Hh) signaling is initiated at primary cilia by the ligand
      triggered accumulation of Smoothened (Smo) in the ciliary membrane. The
      underlying biochemical mechanisms remain unknown. We find that Hh agonists
      promote the association between Smo and Evc2, a ciliary protein that is defective
      in two human ciliopathies. The formation of the Smo-Evc2 complex is under strict
      spatial control, being restricted to a distinct ciliary compartment, the EvC
      zone. Mutant Evc2 proteins that localize in cilia but are displaced from the EvC
      zone are dominant inhibitors of Hh signaling. Disabling Evc2 function blocks Hh
      signaling at a specific step between Smo and the downstream regulators protein
      kinase A and Suppressor of Fused, preventing activation of the Gli transcription
      factors. Our data suggest that the Smo-Evc2 signaling complex at the EvC zone is
      required for Hh signal transmission and elucidate the molecular basis of two
      human ciliopathies.

PMID- 22981990
TI  - Development and validation of a real-time RT-PCR assay for generic detection of
      pospiviroids.
AB  - In many countries phytosanitary regulations apply to Potato spindle tuber viroid,
      because it can cause serious diseases in potato and tomato crops. Other
      pospiviroids, some of which are distributed widely in ornamental crops, can cause
      similar diseases. Consequently, there is a need for a reliable and cost-effective
      generic testing method. An assay was developed that detects all known species of
      the genus Pospiviroid, using real-time RT-PCR based on TaqMan technology. This
      GenPospi assay consists of two reactions running in parallel, the first targeting
      all pospiviroids, except Columnea latent viroid, the second specifically
      targeting the latter viroid (already published). To monitor the RNA extraction a
      nad5 internal control was included. Method validation on tomato leaves showed
      that the GenPospi assay detects all pospiviroids up to a relative infection rate
      of 0.13% (equals 770 times dilution). The assay was specific because no cross
      reactivity was observed with other viroids, viruses or nucleic acid from plant
      hosts. Repeatability and reproducibility were 100% and the assay appeared robust
      in an inter-laboratory comparison. The GenPospi assay has been shown to be a
      suitable tool for large-scale screening for all known pospiviroids. Although it
      has been validated for tomato leaves it can potentially be used for any crop.

PMID- 22981991
TI  - Clinical characteristics and mortality of heart failure. INCAex study.
AB  - BACKGROUND AND OBJECTIVES: Heart failure is responsible for a major part of
      hospital health expenditure and the third cause of cardiovascular death. To
      describe the evolution of clinical features, and factors related to prognosis of
      patients admitted due to decompensated heart failure in a region of Extremadura
      during a period 10 years. PATIENTS AND METHODS: Observational, retrospective and
      single centre study of consecutive patients admitted due to decompensated heart
      failure in a general hospital in the province of Badajoz, during the period
      2000/2009. RESULTS: A total of 2220 patients with mean age of 76.3 (SD+/-10.1),
      being 54% female were included in the study. Stratified into four periods (30
      months each), a significant increase in patients over 75 years was observed (55
      vs. 71%; P<.001), as well as an increase in the prescription of beta blockers at
      discharge (12 vs. 34%, P<.001), statins (8 vs. 31%; P<.001), and oral
      anticoagulants (13 vs. 25%; P<.001). Hospital mortality significantly decreased
      from 13 to 8% (P<.01), and from 30 to 23% (P<.01) at one year follow-up. Age (HR
      per year=1.04 [95% CI: 1.02 to 1.05]), diabetes (HR=1.35 [95% CI: 1.11 to 1.66])
      and chronic renal failure (HR=1.49 [95% CI: 1.18 to 1.87]) were identified as
      independent predictors of all-cause mortality at one year of follow-up.
      CONCLUSIONS: Total mortality in patients with decompensated heart failure has
      declined significantly over the last decade, despite the increasing age. Age,
      diabetes and chronic renal failure were independent predictors of total mortality
      at one year. Oral anticoagulation was a protective factor.

PMID- 22981992
TI  - Osteoarthritis year 2012 in review.

PMID- 22981993
TI  - Peptide reactivity assay using spectrophotometric method for high-throughput
      screening of skin sensitization potential of chemical haptens.
AB  - Haptens must react with cellular proteins to be recognized by antigen presenting
      cells. Therefore, monitoring reactivity of chemicals with peptide/protein has
      been considered an in vitro skin sensitization testing method. The reactivity of
      peptides with chemicals (peptide reactivity) has usually been monitored by
      chromatographic methods like HPLC or LC/MS, which are robust tools for monitoring
      common chemical reactions but are rather expensive and time consuming. Here, we
      examined the possibility of using spectrophotometric methods to monitor peptide
      reactivity. Two synthetic peptides, Ac-RWAACAA and Ac-RWAAKAA, were reacted with
      48 chemicals (34 sensitizers and 14 non-sensitizers). Peptide reactivity was
      measured by monitoring unreacted peptides with UV-Vis spectrophotometer using
      5,5'-dithiobis-2-nitrobenzoic acid as a detection reagent for the free thiol
      group of cysteine-containing peptide or fluorometer using fluorescamineTM as a
      detection reagent for the free amine group of lysine-containing peptide.
      Chemicals were categorized as sensitizers when they induced more than 10%
      depletion of cysteine-containing peptide or 20% depletion of lysine-containing
      peptide. The sensitivity, specificity, and accuracy of this method were 82.4%,
      85.7%, and 83.3%, respectively. These results demonstrate that spectrophotometric
      methods can be easy, fast, and high-throughput screening tools for the prediction
      of the skin sensitization potential of chemical haptens.

PMID- 22981994
TI  - Ovavesicula popilliae (Microsporidia: Ovavesiculidae) spore production in
      naturally infected adult Japanese beetles (Coleoptera: Scarabaeidae).
AB  - Ovavesicula popilliae is a microsporidian that infects both Japanese beetle
      larvae and adults. This is the first study quantifying the number of O. popilliae
      spores produced by Japanese beetle adults. Mean spore production per adult
      Japanese beetle was 2.67 * 10(7) (SE +/- 4.65 * 10(6)) spores with a range of
      1.46 * 10(6)-1.02 * 10(8). The number of spores produced per host is similar to
      other microsporidian species and may help explain the speed with which this
      pathogen has spread from introduction sites to surrounding areas.

PMID- 22981995
TI  - Perezia Microsporidia vs. Perezia Viridiplantae: Homonymy under the ICN with
      comments on jurisdiction of the ICN or ICZN over nomenclature of the
      Microsporidia and a brief discussion of this microsporidian genus and its
      species.
AB  - Until recently, the taxon PereziaLeger and Duboscq (1909) (Fungi: Microsporidia)
      (non-La Gasca, 1811, Viridiplantae: Asteraceae) was a preoccupied name because
      both it and its senior homonym were regulated under the International Code of
      Nomenclature of Algae, Fungi, and Plants. This meant that the microsporidian
      genus name required replacement, as did Pereziidae Loubes [sic], Loubes et al.
      (1977), as that name was based on a homonymous genus name and therefore
      illegitimate. However, a recent decision by the ICN to return microsporidians to
      the auspices of the International Code of Zoological Nomenclature removes this
      homonymy, but causes a potential problem because current language of the ICZN is
      not written in a way that allows microsporidians to return to its jurisdiction.
      Language in the ICZN requires modification in order to avoid microsporidians
      becoming "code orphans." The species of Perezia Leger and Duboscq are reviewed.

PMID- 22981996
TI  - Deletion of egt is responsible for the fast-killing phenotype of natural deletion
      genotypes in a Spodoptera frugiperda multiple nucleopolyhedrovirus population.
AB  - A Nicaraguan population of Spodoptera frugiperda multiple nucleopolyhedrovirus,
      SfMNPV-NIC, includes fast-killing genotypes with deletions in the egt region.
      Four bacmid based recombinants were constructed to determine the role of egt in
      this phenotype. SfdelF bacmid encompassed the deletion found in the NIC-F
      genotype. Sfdel3AP2 bacmid was constructed using the deletion reported in SfMNPV
      3AP2 (Missouri, fast-killing isolate), whereas Sfdelegt and Sfdel27 bacmids
      lacked the single genes egt and the adjacent sf27 gene, respectively. No
      significant differences were observed in occlusion body (OB) concentration
      mortality metrics (LC(50) values) among the viruses. Larvae infected by NIC-B (a
      natural genotype with the largest genome), Sfbac (a bacmid with NIC-B genome) and
      Sfdel27 survived significantly longer than insects infected by NIC-F, SfdelF,
      SfMNPV-3AP2, Sfdel3AP2 or Sfdelegt. Fast-killing viruses produced ~6-13-fold
      fewer OBs/larva compared to other viruses tested. We conclude that
      deletion/disruption of egt is responsible for the fast-killing phenotypes of
      naturally-occurring genotypes in SfMNPV populations from Missouri and Nicaragua.

PMID- 22981997
TI  - The pleiotropic effects of vitamin D in bone.
AB  - A current controversial question related to vitamin D supplementation is what
      level of serum 25-hydroxyvitamin D3 (25(OH)D3) is required to reduce the
      incidence of osteoporotic fractures. The reasoning behind vitamin D
      supplementation has been mostly derived from the role of vitamin D to promote
      intestinal calcium absorption and reduce bone resorption. While minimum 25(OH)D3
      levels of 20nmol/L are required for sufficient intestinal calcium absorption to
      prevent osteomalacia, the mechanistic details of how higher 25(OH)D3 levels, well
      beyond that required for optimal calcium absorption, are able to prevent
      fractures and increase bone mineral density is unclear. Substantial evidence has
      arisen over the past decade that conversion of 25(OH)D3 to 1,25(OH)2D3via the 1
      alpha hydroxylase (CYP27B1) enzyme in osteoblasts, osteocytes, chondrocytes and
      osteoclasts regulates processes such as cell proliferation, maturation and
      mineralization as well as bone resorption, which are all dependent on the
      presence the of the vitamin D receptor (VDR). We and others have also shown that
      increased vitamin D activity in mature osteoblasts by increasing levels of VDR or
      CYP27B1 leads to improved bone mineral volume using two separate transgenic mouse
      models. While questions remain regarding activities of vitamin D in bone to
      influence the anabolic and catabolic processes, the biological importance of
      vitamin D activity within the bone is unquestioned. However, a clearer
      understanding of the varied mechanisms by which vitamin D directly and indirectly
      influences mineral bone status are required to support evidence-based
      recommendations for vitamin D supplementation to reduce the risk of fractures.
      This article is part of a Special Issue entitled 'Vitamin D workshop'.

PMID- 22981998
TI  - The first identification of rare human group A rotavirus strain G3P[10] with
      severe infantile diarrhea in eastern India.
AB  - During an ongoing surveillance for diarrheal pathogens, an unusual human group A
      rotavirus strain G3P[10] (RVA/Human-wt/IND/mcs60/2011/G3P[10]) was detected in a
      stool sample of a 14 months old girl child with acute diarrhea in Kolkata,
      eastern India. The VP7 nucleotide sequence of this strain revealed a close
      phylogenetic relationship to the prototype G3 strain AU-1 and Australian feline
      strain Cat2, whereas, the VP4 gene segment was closely related to the G8P[10]
      rotavirus 69M from Indonesia. Analysis of 11 gene segments of this unusual
      G3P[10] strain demonstrates a complex evolutionary pattern, with genes possibly
      derived from the group A rotaviruses of human DS-1-like and AU-1-like strains of
      simian and caprine host species. To our knowledge, this is the first complete
      genotyping report of any G3P[10] rotavirus, worldwide.

PMID- 22981999
TI  - Evolutionary and ecological factors underlying the tempo and distribution of
      yellow fever virus activity.
AB  - Yellow fever virus (YFV) is historically one of the most important viruses to
      affect human populations. Despite the existence of highly effective vaccines for
      over 70 years, yellow fever remains a significant and re-emerging cause of
      morbidity and mortality in endemic and high-risk regions of South America and
      Africa. The virus may be maintained in sylvatic enzootic/epizootic, transitional
      and urban epidemic transmission cycles with geographic variation in terms of
      levels of genetic diversity, the nature of transmission cycles and patterns of
      outbreak activity. In this review we consider evolutionary and ecological factors
      underlying YFV emergence, maintenance and spread, geographic distribution and
      patterns of epizootic/epidemic activity.

PMID- 22982000
TI  - Neurocysticercosis presenting as a vertical one-and-a-half syndrome with
      associated contralesional horizontal gaze paresis.
AB  - We describe a patient presenting with vertical one-and-a-half syndrome and
      concomitant contralesional horizontal gaze paresis as the result of a solitary
      neurocysticercosis (NCC) lesion in the right midbrain extending into the
      thalamomesencephalic junction. The patient received an albendazole-dexamethasone
      course which resulted in resolution of his symptoms. The neuro-ophthalmological
      complications of NCC are reviewed and the clinical topography of the neuro
      ophthalmological findings of this unusual observation are discussed.

PMID- 22982002
TI  - Late-onset epilepsy in children with acute febrile encephalopathy with prolonged
      convulsions: A clinical and encephalographic study.
AB  - The aim of this study is to analyze the characteristics of epilepsies as the
      sequelae of acute febrile encephalopathy with prolonged convulsions during
      childhood. Sixteen patients (M:F=9:7) aged 2-13years (mean 6.1years) with history
      of febrile acute encephalopathy were retrospectively reviewed. These patients
      experienced febrile encephalopathy at the age of 11months to 4years, with 11
      individuals presenting with findings of a biphasic clinical course (n=5), frontal
      predominant (n=8) lesions, and/or reduced diffusivity in the cerebral white
      matter on magnetic resonance imaging (MRI; n=3). The remaining 5 patients had
      unilateral lesions that manifested the phenotype of hemiconvulsion-hemiplegia
      epilepsy syndrome (HHES). Epilepsy emerged with a latent period of 2months to
      2years after the acute phase of febrile encephalopathy. Head nodding or spasm
      with subsequent motion arrest and brief tonic seizures were the main seizure
      phenotypes. Ictal records of epileptic seizures were available in 9 patients.
      Epileptiform discharges with a focal or uneven distribution appeared at the
      seizure onset and lasted less than 1s in all patients; these were followed by
      either generalized attenuation or fast activity in 8 patients with head nodding,
      spasm, or brief tonic seizures, and by localized fast activity in 1 patient with
      versive tonic seizures. Notably, the seizure onset area was often located outside
      the severe lesions on MRI, i.e., in the parietal areas in patients with frontal
      predominant lesions, and in the spared hemisphere of HHES. Although
      phenobarbital, zonisamide, carbamazepine, clobazam, clonazepam, and clorazepate
      were partially effective in some patients, daily seizures persisted in 11
      patients. Callosotomy was performed in 2 patients, and beneficial effects were
      observed in both. These characteristics suggested a broad distribution of
      augmented excitability in these patients, resulting in the rapid propagation of
      epileptic activity in the initial phase of ictal phenomena. Thus, this study
      investigates the most severe subgroup of epilepsy following febrile acute
      encephalopathy and provides the basis for further exploration of the pathogenesis
      and treatment of characteristic seizures in this population.

PMID- 22982003
TI  - Experimental contributions to cognitive neuroscience theories of memory: a
      special issue in recognition of the contribution of Andrew Mayes.

PMID- 22982001
TI  - Association between variations in coagulation system genes and carotid plaque.
AB  - OBJECTIVE: Genetic variation in coagulation and fibrinolysis may affect the
      development of subclinical atherosclerosis modifying the risk of stroke and
      cardiovascular disease. However, data on the relationship between subclinical
      atherosclerosis and genes involved in the coagulation system are sparse. The
      objective of this study is to examine the association between single nucleotide
      polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque
      phenotypes. METHODS: From the Genetic Determinants of Subclinical Carotid Disease
      Study, 287 Dominicans were examined for carotid plaque presence, thickness, and
      surface irregularity by high-resolution B-mode carotid ultrasound. Logistic
      regression was used to test for association between 101 SNPs in 23 coagulation
      system genes and plaque phenotypes while controlling for age, sex, smoking,
      hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions
      between genes were examined. A follow-up of SNPs in moderate to high (r(2)>0.25)
      linkage disequilibrium (LD) with those implicated in the discovery analysis (p <=
      0.01) was performed in an independent sample of 301 Dominicans. RESULTS: The
      prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean
      age (65 +/- 8 discovery; 65 +/- 9 follow-up) of the participants was similar in
      both datasets. Two genes (vWF and THBS1) were associated (p <= 0.01) with plaque
      size and surface irregularity. In follow-up, 5 SNPs in vWF were associated (p <=
      0.05) with plaque size. SERPINE1 was an additional gene of interest in the
      haplotype and interaction analyses. CONCLUSIONS: Variation in the vWF, THBS1, and
      SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic
      plaque.

PMID- 22982004
TI  - New recommendations for the categorization of cutaneous features of congenital
      melanocytic nevi.
AB  - BACKGROUND: The diameter of congenital melanocytic nevi (CMN) has served as the
      lone criterion for determining risks of adverse outcomes such as melanoma. A
      standardized description of additional morphologic features is needed. OBJECTIVE:
      We sought to develop a consensus-based standardized categorization of cutaneous
      features of CMN and to test agreement among experts on the proposed scheme.
      METHODS: An interdisciplinary group of experts in the field of CMN was surveyed
      using a detailed questionnaire. Applicability of the expert consensus-based
      scheme was tested for interobserver agreement. RESULTS: The principal variable of
      the consensus-based categorization is CMN size, based on maximal diameter the CMN
      is projected to attain by adulthood. CMN size categories include: small (<1.5
      cm); medium (M1: 1.5-10 cm, M2: >10-20 cm); large (L1: >20-30 cm, L2: >30-40 cm);
      and giant (G1: >40-60 cm, G2: >60 cm). In addition, number of satellite nevi in
      the first year of life is categorized into none, 1 to 20, more than 20 to 50, and
      more than 50 satellites. Additional descriptors of CMN include anatomic
      localization, color heterogeneity, surface rugousity and presence of
      hypertrichosis (described as none, moderate, marked), and presence of dermal or
      subcutaneous nodules (none, scattered, extensive). Assessment of consistency
      among 3 experts showed moderate to excellent interobserver agreement for
      categorization of the clinical descriptors (kappa values 0.54-0.93). LIMITATIONS:
      Applicability of the proposed scheme was tested in a virtual setting and only
      among experts. CONCLUSION: The proposed categorization scheme for CMN was agreed
      upon by experts and showed good interobserver agreement. Such standardized
      reporting of patients with CMN facilitates the development of an international
      clinical database for the study of large and giant CMN.

PMID- 22982006
TI  - Effect of geometry of hydrodynamically cavitating device on degradation of orange
      G.
AB  - In this research work, we have carried out geometric optimization of different
      cavitating devices using degradation of orange-G dye [OG] as a model pollutant.
      Three different cavitating devices viz. orifice plate, circular venturi and slit
      venturi were optimized and the degradation of orange-G dye was studied. The
      optimization of all three cavitating devices was done in terms of fluid inlet
      pressure to the cavitating devices and cavitation number. The effect of pH and
      initial concentration of the dye on the degradation rate was also studied. The
      geometry of cavitating device (flow cross sectional area, perimeter, shape, etc.)
      was found to be an important parameter in getting the maximum cavitational effect
      using hydrodynamic cavitation. The cavitational yield of all three cavitating
      devices were compared on the basis of mg of total organic carbon (TOC) reduction
      per unit energy supplied. The slit venturi gives almost 50% higher degradation
      rate and cavitational yield among all three cavitating devices studied for the
      same amount of energy supplied.

PMID- 22982005
TI  - Microarray, gene sequencing, and reverse transcriptase-polymerase chain reaction
      analyses of a cryptic PML-RARA translocation.
AB  - Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myeloid
      leukemia (AML) specifically characterized by the t(15;17)(q22;q12) translocation.
      The t(15;17) results in the fusion of the promyelocytic leukemia (PML) and
      retinoic acid receptor alpha (RARA) genes. Rare cryptic fusions often associated
      with small genomic insertions can best be detected by reverse transcriptase
      polymerase chain reaction (RT-PCR) although conventional chromosomal studies or
      even fluorescence in situ hybridization (FISH) analyses appear normal. We report
      here an APL clone with a cryptic PML-RARA fusion that returned negative results
      by both karyotyping and fluorescence in situ hybridization (FISH), but returned
      positive results by RT-PCR analysis. A single nucleotide polymorphism (SNP)
      microarray analysis was used in this case to help resolve the discordance,
      revealing a 49-kilobase intragenic PML gene duplication. A dual color dual fusion
      PML-RARA FISH probe set identified a small, extra PML signal in a chromosome
      other than 15 or 17. Although coinsertion of a RARA sequence could be detected by
      neither FISH nor array, the RT-PCR positivity is consistent with this fusion
      "ectopic" to the natural gene loci. The findings highlight the clinical utility
      of microarray in cases of cryptic PML-RARA fusion.

PMID- 22982007
TI  - Ultrasound-assisted coating of silk yarn with sphere-like Mn3O4 nanoparticles.
AB  - The growth of sphere-like trimanganese tetraoxide (Mn(3)O(4)) nanoparticles on
      silk fiber was achieved by sequential dipping in an alternating bath of potassium
      hydroxide and manganese(II) nitrate under ultrasound irradiation. Some parameters
      such as the effect of pH, numerous sequential dipping and ultrasonic irradiation
      on growth of the nanoparticles have been studied. The samples were characterized
      with powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and
      wavelength dispersive X-ray (WDX).

PMID- 22982008
TI  - Ultrasound effects on the degradation kinetics, structure and rheological
      properties of apple pectin.
AB  - The effects of ultrasound on the molecular weight of apple pectin were
      investigated. The structure and rheological properties of the degradation
      products were also tentatively identified by High Performance Liquid
      Chromatography-Photodiode Array Detector (HPLC-PAD), Infrared spectroscopy (IR),
      Nuclear Magnetic Resonance spectroscopy (NMR) and Rheometer. The results
      indicated that the weight-average molecular weight of apple pectin decreased
      obviously after ultrasound treatment. The molecular weight of degradation
      products had a uniform and narrow distribution. Ultrasound intensity and
      temperature play an important role in the degradation reaction. Degradation
      kinetics model of apple pectin fitted to 1/M(t) - 1/M(0) = kt from 5 to 45 
      degrees C. The degree of methylation of apple pectin reduced according to IR
      analysis when ultrasound was applied. Ultrasound treatment could not alter the
      primary structure of apple pectin according to the results determined by HPLC, IR
      and NMR. Meanwhile, the viscosity of apple pectin was 10(3) times as large as
      that of ultrasound-treated apple pectin. The ultrasound-treated apple pectin
      showed predominantly viscous responses (G' < G") over the same frequency range.
      The results suggested that ultrasound provided a viable alternative method for
      the modification of pectin.

PMID- 22982009
TI  - Functional MRI evidence for a role of ventral prefrontal cortex in tinnitus.
AB  - It has long been known that subjective tinnitus, a constant or intermittent
      phantom sound perceived by 10 to 15% of the adult population, is not a purely
      auditory phenomenon but is also tied to limbic-related brain regions. Supporting
      evidence comes from data indicating that stress and emotion can modulate
      tinnitus, and from brain imaging studies showing functional and anatomical
      differences in limbic-related brain regions of tinnitus patients and controls.
      Recent studies from our lab revealed altered blood oxygen level-dependent (BOLD)
      responses to stimulation at the tinnitus frequency in the ventral striatum
      (specifically, the nucleus accumbens) and gray-matter reductions (i.e.,
      anatomical changes) in ventromedial prefrontal cortex (vmPFC), of tinnitus
      patients compared to controls. The present study extended these findings by
      demonstrating functional differences in vmPFC between 20 tinnitus patients and 20
      age-matched controls. Importantly, the observed BOLD response in vmPFC was
      positively correlated with tinnitus characteristics such as subjective loudness
      and the percent of time during which the tinnitus was perceived, whereas
      correlations with tinnitus handicap inventory scores and other variables known to
      be affected in tinnitus (e.g., depression, anxiety, noise sensitivity, hearing
      loss) were weaker or absent. This suggests that the observed group differences
      are indeed related to the strength of the tinnitus percept and not to an
      affective reaction to tinnitus. The results further corroborate vmPFC as a region
      of high interest for tinnitus research.This article is part of a Special Issue
      entitled: Tinnitus Neuroscience.

PMID- 22982010
TI  - Electrically tunable organic bioelectronics for spatial and temporal manipulation
      of neuron-like pheochromocytoma (PC-12) cells.
AB  - BACKGROUND: Organic bioelectronic devices consisting of alternating poly(3,4
      ethylenedioxythiophene) (PEDOT) and reduced graphite oxide (rGO) striped
      microelectrode arrays were fabricated by lithography technology. It has been
      demonstrated that the organic bioelectronic devices can be used to spatially and
      temporally manipulate the location and proliferation of the neuron-like
      pheochromocytoma cells (PC-12 cells). METHODS: By coating an electrically labile
      contact repulsion layer of poly(l-lysine-graft-ethylene glycol) (PLL-g-PEG) on
      the PEDOT electrode, the location and polarity of the PC-12 cells were confined
      to the rGO electrodes. RESULTS: The outgrowth of spatially confined bipolar
      neurites was found to align along the direction of the 20MUm wide electrode. The
      location of the PC-12 cells can also be manipulated temporally by applying
      electrical stimulation during the neurite differentiation of PC-12 cells,
      allowing the PC-12 cells to cross over the boundary between the PEDOT and the rGO
      regions and construct neurite networks in an unconfined manner where the contact
      repulsive coating of PLL-g-PEG was removed. CONCLUSIONS: This adsorption and
      desorption of the PLL-g-PEG without and with electrical stimulation can be
      attributed to the tunable surface properties of the PEDOT microelectrodes, whose
      surface charge can switch from being negative to positive under electrical
      stimulation. GENERAL SIGNIFICANCE: The electrically tunable organic
      bioelectronics reported here could potentially be applied to tissue engineering
      related to the development and regeneration of mammalian nervous systems. The
      spatial and temporal control in this device would also be used to study the
      synapse junctions of neuron-neuron contacts in both time and space domains. This
      article is part of a Special Issue entitled Organic Bioelectronics - Novel
      Applications in Biomedicine.

PMID- 22982011
TI  - Evaluation of the antimycobacterium activity of the constituents from Ocimum
      basilicum against Mycobacterium tuberculosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum basilicum belongs to the genus Ocimum
      (Lamiaceae). Many species of this genus including O. basilicum have been
      traditionally used for the treatment of a variety of diseases including
      respiratory diseases and symptoms of tuberculosis. AIM OF STUDY: The aim of the
      study was to evaluate the activity of pure constituents of O. basilicum, a plant
      used in traditional medicine to treat respiratory diseases including symptoms of
      tuberculosis, against Mycobacterium tuberculosis H37Rv. MATERIALS AND METHODS:
      The crude methanolic extract from the aerial parts (leaves, fruits and flowers)
      of the plant was separated into EtOAc and water subextracts and the EtOAc
      subextract was further divided into acidic and neutral fractions. Each of these
      was subjected to fractionation through column chromatography followed by prep.
      TLC. Several pure compounds were thus isolated and their activity was determined
      against M. tuberculosis H37Rv using MABA assay. RESULTS: Nine compounds were
      assayed for antituberculosis activity which exhibited upto 49% inhibition of M.
      tuberculosis H37Rv at 6.25 MUg/mL. These include one new compound bacilicin, the
      structure of which was elucidated based on 2D-NMR (HSQC, HMBC, COSY and NOESY)
      and Ms spectral analysis. The known compounds were identified on the basis of
      comparison of their spectral data with those reported earlier. CONCLUSIONS:
      Inhibition of M. tuberculosis by pure compounds from O. basilicum supports the
      use of this plant in ethnomedicine as a remedy for symptoms of tuberculosis. The
      results also suggest that the activity of the plant may be due to a synergistic
      effect of active compounds including those investigated in the present studies,
      and hence this plant is a potential candidate for obtaining further new
      antituberculosis natural products.

PMID- 22982012
TI  - Prolonged subcutaneous high dose (1 g bid) of Ertapenem as salvage therapy in
      patients with difficult-to-treat bone and joint infection.

PMID- 22982013
TI  - Microbiological markers suggesting high inoculum size at time of surgery are risk
      factors for relapse in patients with Staphylococcus aureus prosthetic joint
      infection.

PMID- 22982015
TI  - The maximum potential market for dengue drugs V 1.0.
AB  - Drugs offer a complementary approach to vaccines for preventing the progression
      of symptoms and onset of the severe manifestations of dengue. Despite the rapid
      maturation of the research and development infrastructure for dengue drugs and
      the increasing frequency of dengue inhibitors reported in the scientific
      literature, the potential size of the market for dengue drugs has not been
      articulated. In the present work, extrapolating from publicly available
      information, we explored the economic burden attributable to dengue, the impact
      of dengue vaccines on clinical case loads, a possible alternative to tiered
      pricing for products for neglected diseases, and defined the maximum potential
      market for a dengue drug. Our projections suggest that in 2006, the annual global
      burden of dengue was US $1.7billion. Our proposed alternative to existing tiered
      pricing structures is that during a temporary period of market exclusivity,
      individual countries would pay 50% of the per-case equivalent of economic costs
      saved through the use of a dengue drug. This would yield prices per case of US
      $13-$239 depending on drug effectiveness and cost of medical and indirect costs
      and lost productivity in different countries. Assuming that such a pricing scheme
      was embraced, the maximum potential market for a dengue drug or drugs that on
      average reduced 40% of economic costs might be as high as US $338million
      annually. Our simulations suggest that dengue vaccines will begin to reduce the
      clinical case load of dengue in 2022, but that the number of cases will not
      decrease below 2006 levels and the proportion vaccinated will remain well below
      that required for the onset of herd immunity during the period of market
      exclusivity after the licensure of the first wave of dengue drugs.

PMID- 22982014
TI  - Impact of cigarette smoking on rates and clinical prognosis of pulmonary
      tuberculosis in Southern Mexico.
AB  - OBJECTIVES: To examine the relationship between cigarette smoking and incidence
      and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes.
      MATERIALS: From 1995 to 2010, we analyzed data from 1062 patients with TB and
      from 2001 to 2004, 2951 contacts in Southern Mexico. Patients with acid-fast
      bacilli or Mycobacterium tuberculosis in sputum samples underwent
      epidemiological, clinical and mycobacteriological evaluation and received
      treatment by the local DOTS program. RESULTS: Consumers of 1-10 (LS) or 11 or
      more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS, 17.74)
      smoker-non-smoker rate ratios were significantly higher for smokers. Smoker
      population was more likely to experience unfavorable treatment outcomes (HS,
      adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and
      2.37). Contacts that smoked had a higher probability of developing active TB (HR
      2.38) during follow up. CONCLUSIONS: Results indicate the need of incorporating
      smoking prevention and cessation, especially among men, into international TB
      control strategies.

PMID- 22982016
TI  - Association between chemerin rs17173608 and vaspin rs2236242 gene polymorphisms
      and the metabolic syndrome, a preliminary report.
AB  - Metabolic syndrome (MeS) is associated with increased risk for type 2 diabetes
      mellitus (T2DM) and cardiovascular disease. There is some evidence indicating
      that adipokines play a role in the development of MeS. The present study was
      aimed to investigate the impact of chemerin rs17173608 and vaspin rs2236242 gene
      polymorphisms with the risk of MeS in a sample of Iranian population. This case
      control study was done on 151 subjects with MeS and 149 without MeS, as defined
      by NCEP-ATPIII. Tetra amplification refractory mutation system-polymerase chain
      reaction (T-ARMS-PCR) was designed to detect the polymorphisms. Our finding
      showed that there are significant differences in genotype frequencies between the
      groups regarding vaspin rs2236242 polymorphism (chi(2)=18.74, p<0.0001). A
      significant protection against MeS was found for vaspin rs2236242 in allele and
      genotypes (Odd Ratio [OR]=0.52; 95% confidence interval [CI]=0.37-0.72; p=0.0001,
      T vs A; OR=0.49; 95%CI=0.29-0.82; p=0.007, TT vs TA and OR=0.17; 95%CI=0.07-0.40;
      p<0.0001, TT vs AA). Our finding showed positive association between chemerin
      rs17173608 polymorphism and risk of MeS (chi(2)=7.70, p=0.021). The G allele
      increased the risk of MeS (OR=1.78; 95% CI=1.14-2.78; p=0.012) as compared to the
      T allele. In conclusion, our data suggest for the first time a significant
      association between vaspin rs2236242 and chemerin rs17173608 polymorphisms and
      the MeS in Zahedan, southeast Iran. Further studies with large sample size and
      different ethnicities are required to confirm our findings.

PMID- 22982017
TI  - Functional characterization and gene expression profiling of superoxide dismutase
      from plant pathogenic phytoplasma.
AB  - The rapid production of huge amounts of reactive oxygen species (ROS) is one of
      the responses of animal and plant cells induced under stress conditions, such as
      pathogenic bacterial infection. To protect against the cytotoxic ROS, it is
      important for pathogenic bacteria to inactivate ROS by employing their
      antioxidant enzymes like superoxide dismutase (SOD). Here, we cloned and
      characterized the sodA gene from the plant pathogenic bacterium, 'Candidatus
      Phytoplasma asteris' OY-W strain. This is the first description of gene
      expression and antioxidant enzymatic activity of SOD from a phytoplasma. We also
      demonstrated the sodA gene product (OY-SOD) functions as Mn-type SOD. Since other
      Mollicutes bacteria such as mycoplasmas do not possess sodA probably due to
      reductive evolution, it is intriguing that phytoplasmas possess sodA despite
      their lack of many metabolic genes, suggesting that OY-SOD may play an important
      role in the phytoplasma colonization of plants and insects. Moreover, Western
      blot analysis and real-time PCR revealed that OY-SOD is expressed when the
      phytoplasma is grown in both plant and insect hosts, suggesting it is functioning
      in both hosts. Possible role of SOD in protection against damage by host-derived
      ROS is discussed.

PMID- 22982018
TI  - Oral bioavailability and gender-related pharmacokinetics of celastrol following
      administration of pure celastrol and its related tablets in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Celastrol is a natural compound extracted from
      the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its
      potential anti-inflammatory and antitumor effects, celastrol has been considered
      as a promising candidate for drug development. AIM OF THE STUDY: To establish a
      sensitive LC-MS/MS method to investigate the pharmacokinetic properties of
      celastrol in rats. Key pharmacokinetic issues of celastrol including oral
      bioavailability, comparative pharmacokinetics between pure compound and tablet
      preparation, as well as gender-related pharmacokinetic difference are to be
      addressed for the first time. MATERIALS AND METHODS: Sprague-Dawley rats were
      administrated an intravenous dose (100 MUg kg(-1)) of pure celastrol and an oral
      dose (1000 MUg kg(-1)) of pure celastrol and TGV tablets (corresponding to 534
      MUg kg(-1) of celastrol), respectively. At different time points, the
      concentration of celastrol in rat plasma was determined by a sensitive and well
      validated LC-MS/MS method. Main pharmacokinetic parameters including area under
      the plasma concentration-time curve (AUC), maximal plasma concentration (Cmax),
      the time for maximal concentration (Tmax) and mean residence time (MRT) were
      estimated by Drug and Statistic1.0 pharmacokinetic software (Chinese
      Pharmacological Association, Anhui, PR China). Statistical analysis was performed
      using two one-side t test with p-values less than 0.05 as the level of
      significance. RESULTS: The standard curve of celastrol showed good linearity in
      the concentration range of 0.11~54.3 ng mL(-1) in our current method, with
      acceptable selectivity, precision, recovery, and stability. The oral absolute
      bioavailability of celastrol significantly increased from 17.06% for pure
      celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral
      administration of TGV tablets, the Cmax and AUC values of celastrol in female
      rats were (32.03+/-8.41) MUg L(-1) and (379.49+/-118.19) MUg h L(-1), which were
      significantly higher (p<0.01) than that in males with the values of (14.31+/
      7.33) MUg L(-1) and (188.17+/-92.33) MUg h L(-1). CONCLUSION: Celastrol
      administered orally in the rat was poorly absorbed into the systemic circulation.
      However, the poor absorption of celastrol could be greatly improved when
      celastrol-containing TGV tablets orally administered, and thereby the oral
      bioavailability of celastrol was significantly increased. As for gender
      difference, female rats showed significantly better absorption of celastrol than
      males.

PMID- 22982019
TI  - Fertility and pregnancy.

PMID- 22982020
TI  - GOAT induced ghrelin acylation regulates hedonic feeding.
AB  - Ghrelin is an orexigenic hormone that regulates homeostatic and reward-related
      feeding behavior. Recent evidence indicates that acylation of ghrelin by the gut
      enzyme ghrelin O-acyl transferase (GOAT) is necessary to render ghrelin maximally
      active within its target tissues. Here we tested the hypothesis that GOAT
      activity modulates food motivation and food hedonics using behavioral
      pharmacology and mutant mice deficient for GOAT and the ghrelin receptor (GHSR).
      We evaluated operant responding following pharmacological administration of acyl
      ghrelin and assessed the necessity of endogenous GOAT activity for operant
      responding in GOAT and GHSR-null mice. Hedonic-based feeding behavior also was
      examined in GOAT-KO and GHSR-null mice using a "Dessert Effect" protocol in which
      the intake of a palatable high fat diet "dessert" was assessed in calorically
      sated mice. Pharmacological administration of acyl-ghrelin augmented operant
      responding; notably, this effect was dependent on intact GHSR signaling. GOAT-KO
      mice displayed attenuated operant responding and decreased hedonic feeding
      relative to controls. These behavioral results correlated with decreased
      expression of the orexin-1 receptor in reward-related brain regions in GOAT-KO
      mice. In summary, the ability of ghrelin to stimulate food motivation is
      dependent on intact GHSR signaling and modified by endogenous GOAT activity.
      Furthermore, GOAT activity is required for hedonic feeding behavior, an effect
      potentially mediated by forebrain orexin signaling. These data highlight the
      significance of the GOAT-ghrelin system for the mediation of food motivation and
      hedonic feeding.

PMID- 22982022
TI  - Complexome profiling identifies TMEM126B as a component of the mitochondrial
      complex I assembly complex.
AB  - Macromolecular complexes are essential players in numerous biological processes.
      They are often large, dynamic, and rather labile; approaches to study them are
      scarce. Covering masses up to ~30 MDa, we separated the native complexome of rat
      heart mitochondria by blue-native and large-pore blue-native gel electrophoresis
      to analyze its constituents by mass spectrometry. Similarities in migration
      patterns allowed hierarchical clustering into interaction profiles representing a
      comprehensive analysis of soluble and membrane-bound complexes of an entire
      organelle. The power of this bottom-up approach was validated with well
      characterized mitochondrial multiprotein complexes. TMEM126B was found to
      comigrate with known assembly factors of mitochondrial complex I, namely CIA30,
      Ecsit, and Acad9. We propose terming this complex mitochondrial complex I
      assembly (MCIA) complex. Furthermore, we demonstrate that TMEM126B is required
      for assembly of complex I. In summary, complexome profiling is a powerful and
      unbiased technique allowing the identification of previously overlooked
      components of large multiprotein complexes.

PMID- 22982023
TI  - Multidrug resistance-associated protein 1 and lung function decline with or
      without long-term corticosteroids treatment in COPD.
AB  - Multidrug resistance-associated protein-1 (MRP1) reduces the oxidative stress
      generated by smoking, a risk factor for Chronic Obstructive Pulmonary Disease
      (COPD). We previously showed that MRP1 variants are associated with the level and
      decline of annual forced expiratory volume in one second (FEV(1)) in the general
      population. Moreover, we showed that MRP1 variants are also associated with
      FEV(1) level and inflammatory markers in COPD patients.We investigate in the
      current study the association of MRP1 protein expression in bronchial biopsies
      with FEV(1) decline in COPD patients using placebo, or inhaled corticosteroids
      (ICS) with or without long-acting beta2-agonists. Additionally we investigate the
      association of MRP1 variants with FEV(1) decline. MRP1 variants (rs212093,
      rs4148382, rs504348, rs4781699, rs35621) were genotyped in 110 COPD patients.
      Associations of MRP1 variants and MRP1 protein expression in bronchial biopsies
      (obtained at baseline, 6 and 30 months) with FEV(1) decline were analyzed using
      linear mixed-effect models. During 30-month ICS treatment, subjects with a
      moderate staining for MRP1 had less FEV(1) decline than those with a weak
      staining. In subjects stopping ICS after 6 months followed by 24-month placebo,
      moderate staining for MRP1 was associated with faster FEV(1) decline than in
      those with a weak staining. None of the variants was associated with FEV(1)
      decline. Our unique study suggests a role of MRP1 protein expression in bronchial
      biopsies in FEV(1) decline occurring selectively in COPD patients with long-term
      (30-month) ICS therapy.

PMID- 22982021
TI  - Sphingolipid signaling in metabolic disorders.
AB  - Sphingolipids, ubiquitous membrane lipids in eukaryotes, carry out a myriad of
      critical cellular functions. The past two decades have seen significant advances
      in sphingolipid research, and in 2010 a first sphingolipid receptor modulator was
      employed as a human therapeutic. Furthermore, cellular signaling mechanisms
      regulated by sphingolipids are being recognized as critical players in metabolic
      diseases. This review focuses on recent advances in cellular and physiological
      mechanisms of sphingolipid regulation and how sphingolipid signaling influences
      metabolic diseases. Progress in this area may contribute to new understanding and
      therapeutic options in complex diseases such as atherosclerosis, diabetes,
      metabolic syndromes, and cancer.

PMID- 22982024
TI  - Changes in solvent accessibility of wild-type and deamidated betaB2-crystallin
      following complex formation with alphaA-crystallin.
AB  - Aberrant protein interactions can lead to aggregation and insolubilization, such
      as occurs during cataract formation. Deamidation, a prevalent age-related
      modification in the lens of the eye, decreases stability of the major lens
      proteins, crystallins. The mechanism of deamidation altering interactions between
      alphaA-crystallin and betaB2-crystallin was investigated by detecting changes in
      solvent accessibility upon complex formation during heating. Solvent
      accessibility was determined by measuring hydrogen/deuterium exchange levels of
      backbone amides by high-resolution mass spectrometry. Deuterium levels in wild
      type betaB2-crystallin increased 50-60% in both domains following complex
      formation with alphaA-crystallin. This increased solvent accessibility indicated
      a general loosening along the backbone amides. Peptides with the greatest
      deuterium increases were located at the buried monomer-monomer interface,
      suggesting that the betaB2 dimer was disrupted. The only region where the
      deuterium levels decreased was in betaB2 peptide 123-139, containing an outside
      loop, and may be a potential site of interaction with alphaA. Mimicking
      deamidation at the betaB2 dimer interface prevented complex formation with
      alphaA. When temperatures were lowered, an alphaA/betaB2 Q70E/Q162E complex
      formed with similar solvent accessibilities as alphaA/WT betaB2. Deamidation did
      not disrupt specific alphaA/betaB2 interactions but favored aggregation before
      complex formation with alphaA. We conclude that deamidation contributes to
      cataract formation through destabilization of crystallins before they can be
      rescued by alpha-crystallin.

PMID- 22982025
TI  - MicroRNA-204 is required for differentiation of human-derived cardiomyocyte
      progenitor cells.
AB  - Human cardiomyocyte progenitor cells (hCMPCs) are cardiac progenitor cells that
      are unique for their efficient differentiation into beating cardiomyocytes
      without requiring co-culture with neonatal cardiomyocytes. hCMPCs have shown
      great potential in preserving the function of infarcted mouse myocardium. MiRNA
      204 has been reported to be up-regulated in differentiated hCMPCs, however, its
      biological significance is unclear. In this study, hCMPC proliferation,
      viability, apoptosis and necrosis were determined using the ELISA Kit
      (colorimetric BrdU detection), Cell Counting Kit-8, and Annexin V and propidium
      iodide staining, respectively. MiRNA-204 inhibition promoted hCMPC proliferation
      without affecting cell viability and the level of apoptosis and necrosis,
      indicating that miRNA-204 might be required for hCMPC differentiation.
      Quantitative reverse transcriptase-polymerase chain reactions were used to detect
      the expression profile of cardiac genes, including MEF2C, GATA-4, Nkx-2.5, TropT,
      betaMHC, and cActin. Cardiac alpha-actin staining was used to quantify the degree
      of differentiation. MiRNA-204 inhibition significantly down-regulated TropT,
      betaMHC, and cActin and reduced differentiation by 47.81% after 2 weeks of
      differentiation induction. Interestingly, miRNA-204 mimics (30 nM) did not
      promote hCMPC proliferation and differentiation. The bioinformatic tool GOmir
      identified the activating transcription factor 2 (ATF-2) as a potential target,
      which was confirmed by Western blot and a luciferase reporter assay. ATF-2
      overexpression promoted hCMPC proliferation, further demonstrating the role
      played by ATF-2 as a target gene of miRNA-204. Therefore, miRNA-204 is required
      for hCMPC differentiation and ATF-2 is a target gene of miRNA-204 in hCMPCs. This
      study indicates that miRNA-204 is among the regulators that drive hCMPC
      proliferation and differentiation, and miRNA-204 might be used to influence cell
      fate.

PMID- 22982026
TI  - Maternal obesity, lipotoxicity and cardiovascular diseases in offspring.
AB  - Maternal obesity has risen dramatically over the past 20 years, by nearly 42% in
      African-Americans and 29% in Caucasians. Maternal obesity is afflicted with many
      maternal obstetric complications in the offspring including high blood pressure,
      obesity, gestational diabetes and increased perinatal morbidity. Maternal
      nutritional environment plays a rather important role in the programming of the
      health set-points in the offspring such as glucose and insulin metabolism, energy
      balance and predisposition to metabolic disorders. In particular, maternal
      obesity is associated with elevated prevalence of cardiovascular diseases in the
      offspring. Evidence from human and experimental studies including rodents and
      nonhuman primates has indicated that maternal obesity or overnutrition programs
      offspring for an increased risk of adult obesity. Maternal obesity or fat diet
      exposure predisposes the onset and development of obesity, insulin resistance,
      cardiac hypertrophy and myocardial contractile anomalies in the offspring. A
      number of mechanisms including elevated hormones (leptin, insulin), nutrients
      (fatty acids, triglycerides and glucose) and inflammatory cytokines have been
      postulated to play a key role in maternal obesity-induced postnatal
      cardiovascular sequelae. In addition, lipotoxicity (accumulation of lipid
      metabolites) resulting from maternal obesity is capable of activating a number of
      stress signaling cascades including pro-inflammatory cytokines and oxidative
      stress to exacerbate maternal obesity-induced cardiovascular complications later
      on in adult life. This mini-review summarizes the recent knowledge with regard to
      the role of lipotoxicity in maternal obesity-induced change in cardiovascular
      function in the offspring. This article is part of a Special Issue entitled
      "Focus on Cardiac Metabolism".

PMID- 22982029
TI  - Development of a serum biomarker panel predicting recurrence in stage I non-small
      cell lung cancer patients.
AB  - OBJECTIVE: Molecular diagnostics capable of prognosticating disease recurrence in
      stage I non-small cell lung cancer (NSCLC) patients have implications for
      improving survival. The objective of the present study was to develop a
      multianalyte serum algorithm predictive of disease recurrence in stage I NSCLC
      patients. METHODS: The Luminex immunobead platform was used to evaluate 43
      biomarkers against 79 patients with resectable NSCLC, with the following cohorts
      represented: stage I (T(1)-T(2)N(0)M(0)) NSCLC without recurrence (n = 37), stage
      I (T(1)-T(2)N(0)M(0)) NSCLC with recurrence (n = 15), and node-positive (T(1)
      T(2)N(1)-N(2)M(0)) NSCLC (n = 27). Peripheral blood was collected before surgery,
      with all patients undergoing anatomic resection. Univariate statistical methods
      (receiver operating characteristics curves and log-rank test) were used to
      evaluate each biomarker with respect to recurrence and outcome. Multivariate
      statistical methods were used to develop a prognostic classification panel for
      disease recurrence. RESULTS: No relationship was found between recurrence and
      age, gender, smoking history, or histologic type. Analysis for all stage I
      patients revealed 28 biomarkers significant for recurrence. Of these, the log
      rank test identified 10 biomarkers that were strongly (P < .01) prognostic for
      recurrence. The Random Forest algorithm created a 6-analyte panel for
      preoperative classification that accurately predicted recurrence in 77% of stage
      I patients tested, with a sensitivity of 74% and specificity of 79%. CONCLUSIONS:
      We report the development of a serum biomarker algorithm capable of
      preoperatively predicting disease recurrence in stage I NSCLC patients.
      Refinement of this panel might stratify patients for adjuvant therapy or
      aggressive recurrence monitoring to improve survival.

PMID- 22982027
TI  - Distinct contributions of Galgt1 and Galgt2 to carbohydrate expression and
      function at the mouse neuromuscular junction.
AB  - At the mammalian neuromuscular junction (NMJ), the CT (cytotoxic T cell)
      carbohydrate antigen [GalNAcbeta1,4[Neu5Ac/Gcalpha2,3]Galbeta1,4GlcNAc-] is a
      unique synaptic cell surface carbohydrate present in both the presynaptic and
      postsynaptic membranes. Here we show that Galgt1, which synthesizes the
      beta1,4GalNAc linkage of the CT carbohydrate on gangliosides, is required for
      presynaptic expression of the CT carbohydrate at the NMJ, while Galgt2, which can
      synthesize the beta1,4GalNAc of the CT carbohydrate on glycoproteins, is required
      for postsynaptic expression. Proper postsynaptic localization of the CT
      carbohydrate also required muscle expression of dystroglycan, a known muscle
      substrate for Galgt2. Transgenic overexpression of Galgt2 in skeletal myofibers
      altered the expression of synaptic muscle proteins and altered neuromuscular
      topography, which was partially NCAM-dependent, while an increase in postsynaptic
      AChR-rich domains was observed in both neuron- and skeletal muscle-specific
      Galgt2 transgenic mice. By contrast, overexpression of Galgt1 in muscle did not
      allow for increased expression of CT carbohydrate on the sarcolemmal membrane and
      instead caused muscle pathology. Loss of Galgt2 increased intracellular
      accumulation of acetylcholine receptors and acetylcholinesterase within skeletal
      myofibers, suggesting an additional role for Galgt2 in neuromuscular stability.
      These experiments demonstrate that Galgt1 and Galgt2 contribute in distinct ways
      to the expression and function of synaptic betaGalNAc-containing carbohydrates at
      the NMJ.

PMID- 22982030
TI  - Aortic dimensions in patients with bicuspid and tricuspid aortic valves.
AB  - OBJECTIVE: Whether patients with bicuspid aortic valves are susceptible not only
      to ascending aortic dilatation but also to dilatation of the remaining aorta is
      uncertain. This study evaluated the possible correlation between ascending aortic
      dilatation and dilatation of the remaining aorta in patients with bicuspid and
      tricuspid aortic valves, respectively. METHODS: The entire aortas of 97 patients
      (bicuspid in 62, tricuspid in 35) undergoing replacement of the ascending aorta
      because of ascending aortic pathology (78 with and 19 without concurrent valve
      pathology) were preoperatively evaluated using computed tomography scanning.
      RESULTS: Aortic dimensions distal to the ascending aorta were smaller in patients
      with bicuspid aortic valves than in patients with tricuspid aortic valves (P <
      .001): proximal arch: 3.20 +/- 0.60 cm/3.80 +/- 0.68 cm; distal arch: 2.90 +/-
      0.60 cm/3.40 +/- 0.50 cm; isthmus, 2.95 +/- 0.60 cm/3.50 +/- 0.60 cm; descending
      aorta: 2.70 +/- 0.50 cm/3.20 +/- 0.65 cm; suprarenal aorta: 2.30 +/- 0.40 cm/2.70
      +/- 0.43 cm; infrarenal aorta: 1.90 +/- 0.48 cm/2.20 +/- 0.35 cm, respectively.
      Concomitant pathologic dilatation of the descending aorta was more common in
      patients with tricuspid aortic valves (37%) than in patients with bicuspid aortic
      valves (5%) (P < .001). Neither valvular pathology nor bicuspid aortic valve
      phenotype influenced the aortic dimensions in the bicuspid group (P > .2).
      CONCLUSIONS: Patients with bicuspid aortic valves and dilatation of the ascending
      aorta consistently had smaller dimensions of the remaining aorta compared with
      patients with tricuspid aortic valves. Concomitant dilatation of the descending
      aorta was predominantly found in patients with tricuspid aortic valves.

PMID- 22982031
TI  - Quantifying the incidence and impact of postoperative prolonged alveolar air leak
      after pulmonary resection.
AB  - OBJECTIVE: Prolonged alveolar air leak (PAAL) is a frequent occurrence after
      lobectomy or lesser resections. The resulting complications and their impact are
      not well understood. Our aims are to prospectively determine the incidence and
      severity of PAAL after pulmonary resection using the Thoracic Morbidity &
      Mortality classification system and to identify risk factors. METHODS: A
      prospective collection of Thoracic Morbidity & Mortality data was performed for
      all consecutive pulmonary resections (n = 380; January 2008 to April 2010).
      Demographics, comorbidities, and preoperative cardiopulmonary assessment were
      retrospectively identified. The incidence and severity (grades I-V) of burden
      from PAAL were quantified using the Ottawa Thoracic Morbidity & Mortality system.
      Risk factors for PAAL and severe PAAL (defined as leading to major intervention,
      organ failure, or death) were sought with univariate and multivariate analyses.
      RESULTS: The incidences of PAAL and severe PAAL were 18% and 4.8%, respectively.
      PAAL prolonged the median hospital stay by 4 days. The majority of complications
      associated with PAAL were limited to pulmonary and pleural categories (90%).
      Significant predictors of PAAL from multivariate analysis include severe
      radiologic emphysema (odds ratio [OR], 2.8; confidence interval [CI], 1.2-6.2),
      histopathologic emphysema (OR, 1.9; CI, 1.1-3.6), percentage of predicted value
      for forced expiratory volume in 1 second less than 80% (OR, 1.9; CI, 1.1-3.3),
      and lobectomy (OR, 4.9; CI, 1.-14.1). Risk factors for severe PAAL include
      radiologic emphysema, percentage of predicted value for forced expiratory volume
      in 1 second less than 80%, forced expiratory volume in 1 second/forced vital
      capacity ratio less than 70%, and intraoperative difficulties (P < .05).
      CONCLUSIONS: PAAL leads to longer hospital stays, and approximately 4.8% of
      patients undergoing pulmonary resection experience PAAL that necessitates
      placement of additional chest drains, bronchoscopy, reoperation, or life support.
      Further study is required to assess the cost-effectiveness of measures to reduce
      PAAL.

PMID- 22982032
TI  - Recurrent catamenial hemopneumothorax treated by coverage with polyglycolic acid
      sheets.

PMID- 22982033
TI  - Extracorporeal life support in patients with severe trauma: an advanced treatment
      strategy for refractory clinical settings.
AB  - OBJECTIVES: Major trauma is a leading cause of death, particularly among young
      patients. New strategies in management are needed to improve poor outcomes in
      cases of severe trauma. Extracorporeal life support (ECLS) has proven to be
      effective in acute cardiopulmonary failure of different causes, even when
      conventional therapies fail. We report our initial experience with ECLS as a
      rescue therapy in severely polytraumatized patients in a refractory clinical
      setting. This study identifies the pre-ECLS characteristics of patients to
      predict the appropriateness of ECLS treatment. METHODS: From December 2008 to May
      2012, 375 patients with polytrauma were treated in the Careggi Teaching Hospital,
      a tertiary-level referral trauma center. Our ECLS team was alerted on 30 patients
      and applied ECLS in 18 adult patients with trauma. We adopted venoarterial ECLS
      in 14 patients with cardiopulmonary failure with refractory shock and venovenous
      ECLS in 4 patients with isolated refractory acute respiratory failure. RESULTS:
      ECLS was initiated at a mean of 359.176 +/- 216.606 (145-950) minutes from
      trauma. In 4 patients, the ECLS treatment failed because of an incapability to
      maintain adequate ECLS flow and perfusion. In 14 patients, efficiently supported
      by ECLS, the cardiac index, mean arterial pressure, blood lactate concentration,
      arterial oxygen tension, arterial carbon dioxide tension, and pH showed
      significant improvement, with normal values reached at 3.5 +/- 1.5 hours.
      CONCLUSIONS: From our data, ECLS seems to be a valuable option to resuscitate
      patients with severe trauma when conventional therapies are insufficient. ECLS is
      safe, feasible, and effective in providing hemodynamic support and blood gas
      exchange.

PMID- 22982034
TI  - Does the Society of Thoracic Surgeons risk score accurately predict operative
      mortality for patients with pulmonary hypertension?
AB  - OBJECTIVE: This study assessed the impact of pulmonary hypertension (PH) on
      morbidity and mortality after the most common cardiac operations and evaluated
      the accuracy of the Society of Thoracic Surgeons (STS) risk model for patients
      with PH. METHODS: At a single center between 1994 and 2010, all adult cardiac
      operations performed with recorded preoperative mean pulmonary arterial pressure
      (MPAP) and STS predicted mortality were reviewed. MPAP was defined as normal (<25
      mm Hg) or as mild (25-34 mm Hg), moderate (35-44 mm Hg), or severe (>= 45 mm Hg)
      PH. Multivariate analysis was performed to elucidate the contribution of PH to
      morbidity and mortality. RESULTS: In all, 3343 patient records were reviewed.
      Coronary artery bypass grafting (CABG) was the most common procedure (67.5%),
      followed by aortic valve replacement (24.9%) and mitral valve procedures (6.3%).
      Postoperative complications and mortality increased with increasing MPAP.
      Multivariable analysis found that both moderate (odds ratio, 7.17; P < .001) and
      severe (odds ratio, 13.73; P < .001) PH were significantly associated with
      increased mortality, even after accounting for STS risk. A subset analysis of
      isolated CABG cases revealed markedly increased mortality for all categories of
      PH (mild odds ratio, 1.99; moderate odds ratio, 11.5; severe odds ratio, 38.9; P
      < .001). CONCLUSIONS: Morbidity and mortality were independently associated with
      PH. Observed mortality was significantly higher than predicted by the STS model
      for patients with moderate and severe PH, particularly in isolated CABG. Addition
      of PH to the STS risk model should be considered, or alternative tools should be
      used to assess risk in these patients.

PMID- 22982035
TI  - The role of methylene blue in serotonin syndrome following cardiac
      transplantation: a case report and review of the literature.

PMID- 22982036
TI  - Two-stage surgical strategy for aortoesophageal fistula: emergent thoracic
      endovascular aortic repair followed by definitive open aortic and esophageal
      reconstruction.

PMID- 22982038
TI  - Effects of single swim stress on changes in TRPV1-mediated plasticity in the
      amygdala.
AB  - By examining the involvement of transient receptor potential vanilloid type 1
      (TRPV1) in the stress modulation of learning and memory processes in mice, we
      evaluated the effects of endovanilloid N-oleoyldopamine (OLDA) on the long-term
      potentiation (LTP) of the lateral nucleus of the amygdala (LA). After high
      frequency stimulation of external capsule fibers we found that LA-LTP is reduced
      in OLDA-treated slices derived from adult C57BL/6 control mice. The specificity
      of the TRPV1 receptor activation by OLDA was confirmed by blocking the OLDA
      induced inhibitory effect on LA-LTP with the specific TRPV1 receptor antagonist
      AMG 9810. The specificity of OLDA was further supported by using TRPV1 deficient
      mice, where the effect of OLDA on LA-LTP was missing. Following exposure to a
      forced swim test (FST) OLDA enhanced LA-LTP in control but not TRPV1-deficient
      mice. The results also show that a short period of acute stress significantly
      impairs LA-LTP. Since we have recently shown the involvement of cannabinoid CB1
      receptors in the mediation of capsaicin-induced inhibitory effects on LA-LTP
      ([23] Zschenderlein et al., 2011), it is reasonable to assume that the OLDA
      induced enhancement of LA-LTP after the forced swim test can be attributed to the
      up-regulation of TRPV1 and the action of ligands such as anandamide on TRPV1. As
      a result, stimulation of TRPV1 receptors rescues LTP in slices derived from swim
      stressed mice.

PMID- 22982039
TI  - Epigenetics.

PMID- 22982037
TI  - Mineralocorticoid receptor antagonism inhibits vein graft remodeling in mice.
AB  - OBJECTIVE: Vein graft failure rates resulting from adverse graft remodeling
      remain high with no effective therapy. The mineralocorticoid receptor (MR) plays
      a role in pathologic arterial remodeling. We demonstrated recently that the MR is
      upregulated in venous tissues after grafting and hypothesized that MR inhibition
      would reduce vein graft remodeling. METHODS: Reverse transcription polymerase
      chain reaction and immunoblotting were used to examine the expression of the MR
      and other components of the renin-angiotensin-aldosterone system in human vein
      and primary human saphenous vein smooth muscle cells (HSVSMC). Adenoviral
      reporter gene assays were used to explore MR transcriptional activity in HSVSMC.
      The effect of MR inhibition on vein graft remodeling in vivo was characterized in
      a mouse vein graft model. RESULTS: Messenger RNAs encoding the MR, 11-beta
      hydroxysteroid dehydrogenase 2, angiotensin type 1 receptor, and the angiotensin
      converting enzyme are expressed in whole HSVSMC. MR and 11-beta-hydroxysteroid
      dehydrogenase 2 protein expression is confirmed, and MR-dependent transcriptional
      regulation is demonstrated at physiologic aldosterone concentrations in HSVSMC.
      Treatment of mice with the MR antagonist spironolactone, at doses that do not
      lower blood pressure (20 mg/kg per day), reduces maximal vein graft intima-media
      thickness by 68%, with an associated reduction in graft inflammatory cell
      infiltration and fibrosis. CONCLUSIONS: MR is expressed in human venous tissue
      and cells and modulates gene expression in HSVSMC in response to physiologic
      aldosterone concentrations. In vivo, MR inhibition reduces vein graft thickening
      and inflammation. These preclinical data support the potential to use MR
      antagonists as novel treatments to preserve vein graft patency.

PMID- 22982040
TI  - TanshinoneIIA ameliorates inflammatory microenvironment of colon cancer cells via
      repression of microRNA-155.
AB  - TanshinoneIIA, an active component derived from a traditional Chinese medicine,
      has anti-inflammatory and anti-cancer effect. However, the mechanisms underlying
      the interaction between anti-inflammation and anti-cancer of TanshinoneIIA remain
      elusive. In the present study, a cell model of inflammation between macrophages
      and colon cancer cells was used. The results showed that TanshinoneIIA inhibited
      the proliferation of inflammation-related colon cancer cells HCT116 and HT-29 by
      decreasing the production of inflammatory cytokines tumor necrosis factor alpha
      (TNF-alpha) and interleukin 6 (IL-6), which generated by macrophage RAW264.7 cell
      line. We identified Phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1
      (SHIP1) was a bona fide target of miR-155. TanshinoneIIA restored the down
      regulated level of SHIP1 protein after lipopolysaccharide (LPS)-stimulation in
      RAW264.7 cells. MicroRNA-155 (miR-155) was up-regulated in macrophages, possibly
      due to the concomitant increase of PU.1, a transcriptional activator of miR-155,
      accounting for decreased SHIP1. Treatment with TanshinoneIIA prevented increased
      PU.1 and hence increased miR-155, whereas aspirin could not. These findings
      support that the interruption of signal conduction between activated macrophages
      and colon cancer cells could be considered as a new therapeutic strategy and miR
      155 could be a potential target for the prevention of inflammation-related
      cancer.

PMID- 22982041
TI  - Lactobacillus reuteri CRL1098 soluble factors modulate tumor necrosis factor
      alpha production in peripheral blood mononuclear cells: involvement of lipid
      rafts.
AB  - The aim of the present study was to evaluate the capacity of Lactobacillus
      reuteri CRL1098 soluble factors (Lr-S) to modulate TNF-alpha production in
      peripheral blood mononuclear cells (PBMC) and to study lipid rafts participation
      in this response. PBMC treated with Lr-S showed a reduced production of TNF
      alpha. In addition, Lr-S treatment activated ERK and p38 MAPK pathways in PBMC.
      Lipid rafts participation in the reduced production of TNF-alpha by PBMC induced
      by Lr-S was verified by lipid rafts disruption with methyl-beta-cyclodextrin and
      the reduction of the Src-tyrosine kinase Lck localization in rafts. Moreover,
      PBMC pre-treatment with Lck inhibitors blocked the effect of Lr-S on TNF-alpha
      production suggesting that activation and mobilization of Lck from lipid rafts
      would be involved in the modulatory effect of L. reuteri CRL1098. A secreted
      peptide of 5785 Da would be responsible of the modulatory effect of CRL1098
      strain. This study demonstrated for the first time the lipid rafts participation
      in a response induced by a beneficial bacterium. Also, these results open new
      possibilities for investigating the molecular mechanisms involved in the
      interaction of probiotic bacterial extracellular compounds with immune cells.

PMID- 22982042
TI  - Anaerostipes hadrus comb. nov., a dominant species within the human colonic
      microbiota; reclassification of Eubacterium hadrum Moore et al. 1976.
AB  - Recent molecular analyses suggest that bacteria related to strains SS2/1 and
      SSC/2, previously reported to be distantly related to Anaerostipes caccae NCIMB
      13811(T), represent one of the ten most abundant phylotypes detected in adult
      human faecal samples. These two strains were isolated as d-lactate-utilizing
      bacteria from faecal samples of a healthy individual. We show here that they
      share >99.9% similarity in 16S rRNA gene sequence with a new butyrate-producing
      isolate recovered from a colonic biopsy of a Crohn's disease patient, and also
      with the sequence reported recently for Eubacterium hadrum ATCC 29173(T).
      Biochemical profiling using API Rapid ID 32A and API ZYM test systems confirmed a
      close phenotypic similarity to E. hadrum ATCC 29173(T), but also indicated that
      the description of this species should be expanded to include the ability to
      produce butyrate from d-lactate and acetate. Phylogenetic analysis confirmed an
      affinity between E. hadrum and members of the genus Anaerostipes (92.3-94.2%
      sequence similarity) belonging to the family Lachnospiraceae (formerly
      Clostridium cluster XIVa). Based on phylogenetic, phenotypic and chemotaxonomic
      evidence it is proposed that E. hadrum be transferred to the genus Anaerostipes
      with the name Anaerostipes hadrus comb. nov. The type strain of A. hadrus comb.
      nov. is =ATCC 29173(T) (=DSM 3319(T) = VP 82-52(T)).

PMID- 22982043
TI  - Identification of a lambda toxin-negative Clostridium perfringens strain that
      processes and activates epsilon prototoxin intracellularly.
AB  - Clostridium perfringens type B and D strains produce epsilon toxin (ETX), which
      is one of the most potent clostridial toxins and is involved in enteritis and
      enterotoxemias of domestic animals. ETX is produced initially as an inactive
      prototoxin that is typically then secreted and processed by intestinal proteases
      or possibly, for some strains, lambda toxin. During the current work a unique C.
      perfringens strain was identified that intracellularly processes epsilon
      prototoxin to an active form capable of killing MDCK cells. This activated toxin
      is not secreted but instead is apparently released upon lysis of bacterial cells
      entering stationary phase. These findings broaden understanding of the
      pathogenesis of type B and D infections by identifying a new mechanism of ETX
      activation.

PMID- 22982044
TI  - Dietary patterns are associated with plasma F2-isoprostanes in an observational
      cohort study of adults.
AB  - Associations between individual foods or nutrients and oxidative markers have
      been reported. Comprehensive measures of food intake may be uniquely informative,
      given the complexity of oxidative systems and the possibility of antioxidant
      synergies. We quantified associations over a 20-year history between three food
      based dietary patterns (summary measures of whole diet) and a plasma biomarker of
      lipid peroxidation, F2-isoprostanes, in a cohort of Americans ages 18-30 at year
      0 (1985-1986). We assessed diet at years 0, 7, and 20 through a detailed history
      of past-month food consumption and supplement use and measured plasma F2
      isoprostanes at years 15 and 20. We created three dietary patterns: (1) a priori
      ("a priori diet quality score") based on hypothesized healthfulness of foods, (2)
      an empirical pattern reflecting high fruit and vegetable intake ("fruit-veg"),
      and (3) an empirical pattern reflecting high meat intake ("meat"). We used linear
      regression to estimate associations between each dietary pattern and plasma F2
      isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7
      average diet and year 15/20 average F2-isoprostanes, n=2718), adjusting for age,
      sex, race, total energy intake, education, smoking, body mass index, waist
      circumference, physical activity, and supplement use. In multivariable-adjusted
      cross-sectional analysis, the a priori diet quality score and the fruit-veg diet
      pattern were negatively, and the meat pattern was positively, associated with F2
      isoprostanes (all p values <0.001). These associations remained statistically
      significant in prospective analysis. Our findings suggest that long-term
      adherence to a diet rich in fruits and vegetables and low in red meat may
      decrease lipid peroxidation.

PMID- 22982045
TI  - Ankaflavin, a novel Nrf-2 activator for attenuating allergic airway inflammation.
AB  - The role of inflammation-induced oxidative stress in the pathogenesis and
      progression of chronic inflammatory airways diseases has received increasing
      attention in recent years. Nuclear factor-erythroid 2 related factor 2 (Nrf-2) is
      the primary transcription factor that regulates the expression of antioxidant and
      detoxifying enzymes. In this study, yellow pigment ankaflavin (AK), derived from
      Monascus-fermented products, elevated nuclear Nrf-2 protein translocation in both
      the A549 lung cell line and the lungs of ovalbumin (OVA)-challenged mice.
      Furthermore, AK increased the mRNA expression of antioxidant enzymes regulated by
      Nrf-2, leading to a reduction in allergen-driven airway inflammation, mucus cell
      hyperplasia, and eosinophilia in OVA-challenged mice. Additionally, AK prevented
      T-cell infiltration and Th2 cytokines including interleukin (IL)-4, IL-5, and IL
      13 generation in bronchial alveolar lavage fluid. The adhesion molecules ICAM-1,
      VCAM-1, and eotaxin were substantially reduced by AK treatment. Importantly, the
      inhibitory effect of AK on adhesion molecule production and immune cell
      infiltration was abolished by Nrf-2 small interfering RNA. This is the first
      study to illustrate that AK acts as a novel Nrf-2 activator for modulating the
      oxidative stress pathway to improve the lung injury and ameliorate the
      development of airway inflammation.

PMID- 22982046
TI  - A compensatory mechanism protects retinal mitochondria from initial insult in
      diabetic retinopathy.
AB  - In the pathogenesis of diabetic retinopathy, an increase in retinal oxidative
      stress precedes mitochondrial dysfunction and capillary cell apoptosis. This
      study is designed to understand the mechanism responsible for the protection of
      mitochondria damage in the early stages of diabetic retinopathy. After 15 days-12
      months of streptozotocin-induced diabetes in rats, retina was analyzed for
      mitochondria DNA (mtDNA) damage by extended length PCR. DNA repair enzyme and
      replication machinery were quantified in the mitochondria, and the binding of
      mitochondrial transcriptional factor A (TFAM) with mtDNA was analyzed by ChIP.
      Key parameters were confirmed in the retinal endothelial cells incubated in 20mM
      glucose for 6-96h. Although reactive oxygen species (ROS) were increased within
      15 days of diabetes, mtDNA damage was observed at 6 months of diabetes. After 15
      days of diabetes DNA repair/replication enzymes were significantly increased in
      the mitochondria, but at 2 months, their mitochondrial accumulation started to
      come down, and mtDNA copy number and binding of TFAM with mtDNA became
      significantly elevated. However, at 6 months of diabetes, the repair/replication
      machinery became subnormal and mtDNA copy number significantly decreased. A
      similar temporal relationship was observed in endothelial cells exposed to high
      glucose. Thus, in the early stages of diabetes, increased mtDNA biogenesis and
      repair compensates for the ROS-induced damage, but, with sustained insult, this
      mechanism is overwhelmed, and mtDNA and electron transport chain (ETC) are
      damaged. The compromised ETC propagates a vicious cycle of ROS and the
      dysfunctional mitochondria fuels loss of capillary cells by initiating their
      apoptosis.

PMID- 22982047
TI  - The peroxidase activity of mitochondrial superoxide dismutase.
AB  - Manganese superoxide dismutase (MnSOD) is an integral mitochondrial protein known
      as a first-line antioxidant defense against superoxide radical anions produced as
      by-products of the electron transport chain. Recent studies have shaped the idea
      that by regulating the mitochondrial redox status and H(2)O(2) outflow, MnSOD
      acts as a fundamental regulator of cellular proliferation, metabolism, and
      apoptosis, thereby assuming roles that extend far beyond its proposed antioxidant
      functions. Accordingly, allelic variations of MnSOD that have been shown to
      augment levels of MnSOD in mitochondria result in a 10-fold increase in prostate
      cancer risk. In addition, epidemiologic studies indicate that reduced glutathione
      peroxidase activity along with increases in H(2)O(2) further increase cancer risk
      in the face of MnSOD overexpression. These facts led us to hypothesize that, like
      its Cu,ZnSOD counterpart, MnSOD may work as a peroxidase, utilizing H(2)O(2) to
      promote mitochondrial damage, a known cancer risk factor. Here we report that
      MnSOD indeed possesses peroxidase activity that manifests in mitochondria when
      the enzyme is overexpressed.

PMID- 22982049
TI  - Transitory phases of autophagic death and programmed necrosis during superoxide
      induced neuronal cell death.
AB  - Neurons can undergo a diverse range of death responses under oxidative stress,
      encompassing apoptosis (caspase-dependent, programmed cell death) to various
      forms of caspase-independent death, including necrosis. We recently showed that
      primary murine cortical neurons exposed acutely to hydrogen peroxide undergo
      caspase-independent death, both autophagic cell death and programmed necrosis. To
      determine how oxidative stress induced by superoxide affects the route to
      cellular demise, we exposed primary cortical neurons to extended superoxide
      insult (provided by exogenous xanthine and xanthine oxidase in the presence of
      catalase). Under these conditions, over 24h, the nitroblue tetrazolium-reducing
      activity (indicative of superoxide) rose significantly during the first 4 to 8h
      and then declined to background levels. As with hydrogen peroxide, this
      superoxide insult failed to activate downstream caspases (-3, -7, and -9).
      Substantial depolarization of mitochondria occurred after 1h, and nuclear
      morphology changes characteristic of oxidative stress became maximal after 2h.
      However, death indicated by plasma membrane permeabilization (cellular uptake of
      propidium iodide) approached maximal levels only after 4h, at which time
      substantial redistribution to the cytosol of death-associated mitochondrial
      intermembrane space proteins, notably endonuclease G, had occurred. Applying
      established criteria for autophagic death (knockdown of Atg7) or programmed
      necrosis (knockdown of endonuclease G), cells treated with the relevant siRNA
      showed significant blockade of each type of cell death, 4h after onset of the
      superoxide flux. Yet at later times, siRNA-mediated knockdown failed to prevent
      death, monitored by cellular uptake of propidium iodide. We conclude that
      superoxide initially invokes a diverse programmed caspase-independent death
      response, involving transient manifestation in parallel of autophagic death and
      programmed necrosis. Ultimately most neurons become overwhelmed by the
      consequences of severe oxidative stress and die. This study reveals the multiple
      phases of neuronal cell death modalities under extended oxidative stress.

PMID- 22982048
TI  - Lipofuscin is formed independently of macroautophagy and lysosomal activity in
      stress-induced prematurely senescent human fibroblasts.
AB  - In the current literature, the lysosomal system is considered to be involved in
      the intracellular formation and accumulation of lipofuscin, a highly oxidized and
      covalently cross-linked aggregate of proteins that fills the lysosomal volume
      during aging. In contrast, our experimental results presented here suggest that
      both the autophagosomes and the lysosomal system are not mandatory for the
      formation of lipofuscin, since that material accumulates in the cytosolic volume
      if autophagy or lysosomal activity is inhibited. However, such an inhibition is
      accompanied by an enhanced toxicity of the formed protein aggregates.
      Furthermore, it could be proven that macroautophagy is responsible for the uptake
      of lipofuscin into the lysosomes.

PMID- 22982050
TI  - NOX1/NADPH oxidase is involved in endotoxin-induced cardiomyocyte apoptosis.
AB  - The functional significance of NOX1/NADPH oxidase in the heart has not been
      explored due to its low expression relative to other NOX homologs identified so
      far. We aimed to clarify the role of NOX1/NADPH oxidase in the septic heart by
      utilizing mice deficient in the Nox1 gene (Nox1(-/Y)). Sepsis was induced by
      intraperitoneal administration of lipopolysaccharides (LPS: 25mg/kg) or cecal
      ligation and puncture (CLP) surgery. A marked elevation of NOX1 mRNA was
      demonstrated in cardiac tissue, which was accompanied by increased production of
      reactive oxygen species (ROS). In Nox1(-/Y) treated with LPS, cardiac dysfunction
      and survival were significantly improved compared with wild-type mice (Nox1(+/Y))
      treated with LPS. Concomitantly, LPS-induced cardiomyocyte apoptosis and
      activation of caspase-3 were alleviated in Nox1(-/Y). The level of phosphorylated
      Akt in cardiac tissue was significantly lowered in Nox1(+/Y) but not in Nox1(-/Y)
      treated with LPS or that underwent CLP surgery. Increased oxidation of cysteine
      residues of Akt and enhanced interaction of Akt with protein phosphatase 2A
      (PP2A), a major phosphatase implicated in the dephosphorylation of Akt, were
      demonstrated in LPS-treated Nox1(+/Y). These responses to LPS were significantly
      attenuated in Nox1(-/Y). Taken together, ROS derived from NOX1/NADPH oxidase play
      a pivotal role in endotoxin-induced cardiomyocyte apoptosis by increasing
      oxidation of Akt and subsequent dephosphorylation by PP2A. Marked up-regulation
      of NOX1 may affect the risk of mortality under systemic inflammatory conditions.

PMID- 22982052
TI  - Nitro-fatty acids as novel electrophilic ligands for peroxisome proliferator
      activated receptors.
AB  - Lipid nitration has been observed during oxidative/nitrative stress conditions
      generating a variety of biomolecules capable of modulating cellular responses.
      This concept has grown as a result of studies with nitro-derivatives of long
      chain unsaturated fatty acids containing a nitroalkene group (nitro-fatty acids).
      This review focuses on the interactions of nitro-fatty acids with members of the
      peroxisome proliferator-activated receptors (PPARs) family. These nuclear
      receptors belong to a superfamily of ligand-activated transcription factors,
      which serve as sensors of lipophilic molecules and regulate the expression of a
      set of genes involved in glucose and lipid metabolism. Here we discuss how nitro
      fatty acids bind and activate PPARs, including the current knowledge of the
      molecular interactions and cell signaling events involved as well as their
      therapeutic potential associated with chronic inflammation and metabolic
      disorders.

PMID- 22982051
TI  - Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular
      endothelial cell dysfunction in vitro.
AB  - 2-Chlorohexadecanal (2-ClHDA), a chlorinated fatty aldehyde, is formed via attack
      on ether-phospholipids by hypochlorous acid (HOCl) that is generated by the
      myeloperoxidase-hydrogen peroxide-chloride system of activated leukocytes. 2
      ClHDA levels are elevated in atherosclerotic lesions, myocardial infarction, and
      neuroinflammation. Neuroinflammatory conditions are accompanied by accumulation
      of neutrophils (an ample source of myeloperoxidase) in the brain. Microvessel
      damage by inflammatory mediators and/or reactive oxidants can induce blood-brain
      barrier (BBB) dysfunction, a pathological condition leading to cerebral edema,
      brain hemorrhage, and neuronal death. In this in vitro study we investigated the
      impact of 2-ClHDA on brain microvascular endothelial cells (BMVEC), which
      constitute the morphological basis of the BBB. We show that exogenously added 2
      ClHDA is subject to rapid uptake and metabolism by BMVEC. Using C16 structural
      analogues of 2-ClHDA we found that the cytotoxic potential decreases in the
      following order: 2-ClHDA>hexadecanal>palmitic acid>2-ClHDA-dimethylacetal. 2
      ClHDA induces loss of barrier function, mitochondrial dysfunction, apoptosis via
      activation of caspase 3, and altered intracellular redox balance. Finally we
      investigated potential protective effects of several natural polyphenols on in
      vitro BBB function. Of the compounds tested, phloretin almost completely
      abrogated 2-ClHDA-induced BMVEC barrier dysfunction and cell death. These data
      suggest that 2-ClHDA has the potential to induce BBB breakdown under inflammatory
      conditions and that phloretin confers protection in this experimental setting.

PMID- 22982053
TI  - Differential effects of developmental hypo- and hyperthyroidism on
      acetylcholinesterase and butyrylcholinesterase activity in the spinal cord of
      developing postnatal rat pups.
AB  - The plasticity and vulnerability of the rat spinal cord (SC) during postnatal
      development has been less investigated compared to other CNS structures. In this
      study, we determined the effects of thyroid hormonal (TH) deficiency and excess
      on postnatal growth and neurochemical development of the rat SC. The growth as
      well as the specific and total activity of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and
      hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and
      were compared to age-matched untreated normal controls. AChE is a cholinergic
      synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and
      neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic
      neurons and associated interneurons. Daily subcutaneous injection of pups with
      thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU)
      in the litter's drinking water were used to induce hyper- and hypothyroidism,
      respectively. Enzyme assays were carried out spectrophotometrically at the above
      mentioned ages, using SC homogenates with acetylthiocholine-chloride as the
      substrate, together with specific cholinesterase inhibitors, which specifically
      target AChE and BuChE. SC weights were significantly lower at P10 and P21 in
      hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism
      significantly reduced both specific and total AChE activity in SC of P10 and P21
      rat pups, while having no effects on the BuChE activity, although total BuChE
      activity was decreased due to reduced total tissue weight. In contrast both
      specific and total AChE activities were markedly and significantly increased
      (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity
      was unaffected by this treatment. The results indicate that hypothyroid condition
      significantly reduces, while hyperthyroidism increases, the postnatal development
      of cholinergic synapses, thereby influencing the functional development of this
      major sensory and motor structure. However, the neurochemical development of glia
      and other non-neuronal cells, where BuChE is mainly localized, is comparatively
      unaffected in these abnormal developmental conditions.

PMID- 22982054
TI  - Dicer is essential for neuronal polarity.
AB  - Dicer, an RNase III endonuclease, is the enzyme which cleaves microRNA (miRNA)
      and small interfering RNA (siRNA) precursors into 21-25 nucleotide species. This
      cleavage is an essential step in the biogenesis of these small noncoding RNA
      molecules. In their mature forms, siRNA and miRNAs function to regulate gene
      expression through different mechanisms (Bartel, 2004). To investigate the role
      of Dicer and microRNAs in neuronal polarity development, we used mice in which
      the RNase III domain of Dicer was conditionally floxed. To knockout Dicer gene,
      hippocampal neurons were electroporated with Cre together with pmaxGFP((r))
      plasmid by Amaxa((r)) Mouse Neuron Nucleofector((r)) Kit. Neuronal polarity was
      analyzed at 3 days in vitro (DIV). Neurons expressing pmaxGFP((r)) showed normal
      polarity. In contrast, the majority of neurons transfected with Cre developed
      multiple axons. We found multiple axons were significantly increasing. Here we
      explore Dicer function in neuronal polarity by inactivating it in the hippocampal
      neuron using the Cre/loxP approach. Neurons which lack Dicer have multiple axons,
      demonstrating that Dicer is essential for neuron polarity, providing evidence
      that Dicer function is required to neuronal development.

PMID- 22982056
TI  - Phytochemicals and their impact on adipose tissue inflammation and diabetes.
AB  - Type 2 diabetes mellitus is an inflammatory disease and the mechanisms that
      underlie this disease, although still incompletely understood, take place in the
      adipose tissue of obese subjects. Concurrently, the prevalence of obesity caused
      by Western diet's excessive energy intake and the lack of exercise escalates, and
      is believed to be causative for the chronic inflammatory state in adipose tissue.
      Overnutrition itself as an overload of energy may induce the adipocytes to
      secrete chemokines activating and attracting immune cells to adipose tissue. But
      also inflammation-mediating food ingredients like saturated fatty acids are
      believed to directly initiate the inflammatory cascade. In addition, hypoxia in
      adipose tissue as a direct consequence of obesity, and its effect on gene
      expression in adipocytes and surrounding cells in fat tissue of obese subjects
      appears to play a central role in this inflammatory response too. In contrast,
      revisiting diet all over the world, there are also some natural food products and
      beverages which are associated with curative effects on human health. Several
      natural compounds known as spices such as curcumin, capsaicin, and gingerol, or
      secondary plant metabolites catechin, resveratrol, genistein, and quercetin have
      been reported to provide an improved health status to their consumers, especially
      with regard to diabetes, and therefore have been investigated for their anti
      inflammatory effect. In this review, we will give an overview about these
      phytochemicals and their role to interfere with inflammatory cascades in adipose
      tissue and their potential for fighting against inflammatory diseases like
      diabetes as investigated in vivo.

PMID- 22982055
TI  - Alpha(1)-adrenergic-mediated eNOS phosphorylation in intact arteries.
AB  - Activation of arterial smooth muscle alpha(1)-adrenergic receptors results in
      vasoconstriction, as well as a secondary release of nitric oxide and slow
      vasodilation, presumably through gap junction communication from smooth muscle to
      endothelium. We hypothesized that this slow vasodilation is due to activation of
      eNOS through phosphorylation at Ser1179 and dephosphorylation at Thr495.
      Phosphorylation was measured by western blot using mouse mesenteric arteries that
      were cannulated and pressurized (75 mm Hg) and treated either by 1) 5 min of
      phenylephrine superfusion (10(-5)M) (PE5), 2) 15 min of phenylephrine (PE15), 3)
      15 min phenylephrine followed by acetylcholine (10(-4)M) (PE+ACh), or 4) 20 min
      time control with no treatment (NT) [4-5 arteries pooled per treatment per blot;
      5 blots performed]. These treatments allowed correlation between vasomotor
      changes, namely maximal constriction (PE5), slow vasodilation (PE15), and maximal
      dilation (PE+ACh), and relative phosphorylation changes. Phosphorylation of eNOS
      at Ser1179 was increased relative to NT by more than 2-fold at PE5 and remained
      similarly increased at PE15 and PE+ACh. Phosphorylation of eNOS at Thr495 was
      less in all treatments relative to NT, but not significantly. Treatment with L
      NAME (10(-4)M) or endothelial denudation indicated that the slow dilation in
      response to phenylephrine was completely due to nitric oxide synthase and was
      endothelial dependent. These results indicate that eNOS phosphorylation at
      Ser1179 occurs before the slow dilation and is not actively involved in this
      vasodilation or dilation to acetylcholine, but may play a permissive role in eNOS
      activation by other mechanisms. It is not yet known what mechanism is responsible
      for Ser1179 phosphorylation with phenylephrine stimulation.

PMID- 22982057
TI  - Cyclic guanosine monophosphate signalling pathway in pulmonary arterial
      hypertension.
AB  - During the last decade, it emerged that cyclic guanosine monophosphate (cGMP) is
      a novel drug target for the treatment of pulmonary arterial hypertension (PAH).
      cGMP regulates many cellular functions, ranging from contractility to growth, of
      relevance to the disease. Generated from guanylyl cyclases in response to
      natriuretic peptides or nitric oxide (NO), cGMP transduces its effects through a
      number of cGMP effectors, including cGMP-regulated phosphodiesterases and protein
      kinases. Furthermore, the cGMP concentration is modulated by cGMP-degrading
      phosphodiesterases. Data to date demonstrate that increasing intracellular cGMP
      through stimulation of GCs, inhibition of PDEs, or both is a valid therapeutic
      strategy in drug development for PAH. New advances in understanding of cGMP are
      unravelled, as well as the pathobiology of PAH. cGMP remains an attractive future
      PAH drug target. This review makes a more detailed examination of cGMP signalling
      with particular reference to PAH.

PMID- 22982058
TI  - Binding of DC-SIGN to glycoproteins expressed in glycoengineered Pichia pastoris.
AB  - Previous studies have shown that glycoproteins expressed in wild-type Pichia
      pastoris bind to Dendritic cell-SIGN (DC-Specific Intercellular adhesion molecule
      3 Grabbing Nonintegrin), a mannose-binding receptor found on dendritic cells in
      peripheral tissues which is involved in antigen presentation and the initiation
      of an immune response. However, the binding of DC-SIGN to glycoproteins purified
      from P. pastoris strains engineered to express humanized N- and O-linked glycans
      has not been tested to date. In this study, the binding of glycoproteins with
      specific high-mannose or human N- and O-linked glycan structures to DC-SIGN was
      tested. Proteins with humanized N-glycans including Man5 structures and O-glycans
      (up to as many as 24) with single mannose chain length showed DC-SIGN binding
      that was comparable to that measured for a CHO-produced IgG1 which lacks O-linked
      mannose. Glycoproteins with wild-type N-glycans and mannotriose and higher O
      glycans bound to DC-SIGN in a manner that was strongly inhibited by either the
      use of enzymatic N-deglycosylation or sodium meta-periodate oxidation. Mannan
      purified from humanized P. pastoris also showed lower ability to inhibit DC-SIGN
      binding to glycoproteins with wild type fungal glycosylation than mannan purified
      from wild type strains. This study shows that humanized P. pastoris can produce
      glycoproteins that do not bind to DC-SIGN.

PMID- 22982059
TI  - Circulating insulin-like growth factors may contribute substantially to insulin
      receptor isoform A and insulin receptor isoform B signalling.
AB  - BACKGROUND: Only a fraction of circulating insulin-like activity is due to
      insulin itself. The aim of this study was to determine total serum insulin-like
      activity mediated via the insulin receptor isoform A (IR-A) and isoform B (IR-B)
      by using kinase receptor activation (KIRA) assays specific for the IR-A and IR-B.
      METHODS: The IR-A and IR-B KIRA assays use human embryonic kidney cells which
      have been transfected with the human IR-A or IR-B gene and quantify serum
      mediated phosphorylation of the IR. RESULTS: Both IR KIRA assays were sensitive
      (detection limit 32 pmol/L) and precise (intra- and inter assay CV: <12% and
      <15%). The EC50s of insulin, IGF-I and IGF-II were 1.4, 11.2 and 6.7 nmol/L for
      the IR-A KIRA assay, and 1.3, 31.0 and 15.7 nmol/L for the IR-B KIRA assay. The
      operational range of both assays allowed for determination of total insulin-like
      activity in human serum. Analysis of serum samples showed that there was a
      significant positive correlation between serum insulin-like and immunoreactive
      insulin concentrations (IR-A: r = 0.56, p = 0.01, IR-B: r = 0.68, p = 0.001).
      Importantly, addition of IGF-I or IGF-II antibodies to human serum samples could
      substantially decrease the endpoint signal in both KIRA assays. CONCLUSIONS: We
      showed that serum IGF-I and IGF-II may substantially contribute to IR signalling.
      Since IR isoform specific KIRA assays also take into account the contribution of
      IGFs present in serum on IR signalling, they may help to gain more insight into
      the roles of IGF mediated IR-A and IR-B activation in health and disease.

PMID- 22982061
TI  - Mechanism of capsaicin receptor TRPV1-mediated toxicity in pain-sensing neurons
      focusing on the effects of Na(+)/Ca(2+) fluxes and the Ca(2+)-binding protein
      calretinin.
AB  - Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is a pain
      sensing, ligand-gated, non-selective cation channel expressed in peripheral
      sensory neurons. Prolonged activation of TRPV1 by capsaicin leads to cell
      swelling and formation of membrane blebs in rat dorsal root ganglion (DRG)
      neurons. Similar results were obtained in NIH3T3 fibroblast cells stably
      expressing TRPV1. Here, we assessed the contribution of Ca(2+) and Na(+) ions to
      TRPV1-mediated changes. Cell swelling was caused by a substantial influx of
      extracellular Na(+) via TRPV1 channels, causing concomitant transport of water.
      In the absence of extracellular Na(+), the membrane blebbing was completely
      inhibited, but Ca(2+) influx did not change under these conditions. Na(+) influx
      was modulated by the intracellular Ca(2+) concentration ([Ca(2+)]i). Elevation of
      [Ca(2+)]i by ionomycin sensitized/activated TRPV1 channels causing cell swelling
      in TRPV1-positive cells. In the absence of extracellular Ca(2+), capsaicin caused
      only little increase in [Ca(2+)]i indicating that the increase in [Ca(2+)]i
      observed after capsaicin application is derived essentially from extracellular
      Ca(2+) and not from internal Ca(2+) stores. In the absence of extracellular
      Ca(2+) also the process of cell swelling was considerably slower. Calretinin is a
      Ca(2+) buffer protein, which is expressed in a subset of TRPV1-positive neurons.
      Calretinin decreased the amplitude, but slowed down the decay of Ca(2+) signals
      evoked by ionomycin. Cells co-expressing TRPV1 and calretinin were less sensitive
      to TRPV1-mediated, capsaicin-induced volume increases. In TRPV1-expressing NIH3T3
      cells, calretinin decreased the capsaicin-induced Ca(2+) and Na(+) influx.
      Swelling and formation of membrane blebs resulted in impaired plasma membrane
      integrity finally leading to cell death. Our results hint towards a mechanistic
      explanation for the apoptosis-independent capsaicin-evoked neuronal loss and
      additionally reveal a protective effect of calretinin; we propose that the Ca(2+)
      buffering capacity of calretinin reduces the susceptibility of calretinin
      expressing DRG neurons against cell swelling/death caused by overstimulation of
      TRPV1 channels. This article is part of a Special Issue entitled:12th European
      Symposium on Calcium.

PMID- 22982060
TI  - Estradiol, acting through estrogen receptor alpha, restores dimethylarginine
      dimethylaminohydrolase activity and nitric oxide production in oxLDL-treated
      human arterial endothelial cells.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide
      (NO) synthase. ADMA accumulation, mainly due to a decreased dimethylarginine
      dimethylaminohydrolase (DDAH) activity, has been related to the development of
      cardiovascular diseases. We investigate whether estradiol prevents the changes
      induced by oxidized low density lipoprotein (oxLDL) on the DDAH/ADMA/NO pathway
      in human umbilical artery endothelial cells (HUAEC). HUAEC were exposed to
      estradiol, native LDL (nLDL), oxLDL and their combinations for 24 h. In some
      experiments, cells were also exposed to the unspecific estrogen receptor (ER)
      antagonist ICI 182780, the specific ERalpha antagonist MPP or specific agonists
      for ERalpha, ERbeta and GPER. ADMA concentration was measured by HPLC and
      concentration of NO by amperometry. Protein expression and DDAH activity were
      measured by immunoblotting and an enzymatic method, respectively. oxLDL, but not
      nLDL, increased ADMA concentration with a concomitant decrease on DDAH activity.
      oxLDL reduced eNOS protein and NO production. Estradiol alone had no effects on
      DDAH/ADMA/NO pathway, but increased the attenuated endothelial NO production
      induced by oxLDL by reduction in ADMA and preventing loss of eNOS protein levels.
      ICI 182780 and MPP completely abolished these effects of estradiol on oxLDL
      exposed cells. ERalpha agonist, but not ERbeta and GPER agonists, mirrored
      estradiol effects on NO production. In conclusion, estradiol restores (1) DDAH
      activity, and therefore ADMA levels, and (2) NO production impaired by oxLDL in
      HUAEC acting through ERalpha.

PMID- 22982062
TI  - Transposable elements and human cancer: a causal relationship?
AB  - Transposable elements are present in almost all genomes including that of humans.
      These mobile DNA sequences are capable of invading genomes and their impact on
      genome evolution is substantial as they contribute to the genetic diversity of
      organisms. The mobility of transposable elements can cause deleterious mutations,
      gene disruption and chromosome rearrangements that may lead to several
      pathologies including cancer. This mini-review aims to give a brief overview of
      the relationship that transposons and retrotransposons may have in the genetic
      cause of human cancer onset, or conversely creating protection against cancer.
      Finally, the cause of TE mobility may also be the cancer cell environment itself.

PMID- 22982063
TI  - Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from
      diabetes.
AB  - Reduced glucose metabolism is an invariant feature of Alzheimer's Disease (AD)
      and an outstanding biomarker of disease progression. Glucose metabolism may be an
      attractive therapeutic target, whether the decline initiates AD pathophysiology
      or is a critical component of a cascade. The cause of cerebral regional glucose
      hypometabolism remains unclear. Thiamine-dependent processes are critical in
      glucose metabolism and are diminished in brains of AD patients at autopsy.
      Further, the reductions in thiamine-dependent processes are highly correlated to
      the decline in clinical dementia rating scales. In animal models, thiamine
      deficiency exacerbates plaque formation, promotes phosphorylation of tau and
      impairs memory. In contrast, treatment of mouse models of AD with the thiamine
      derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and
      reverses memory deficits. Diabetes predisposes to AD, which suggests they may
      share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in
      diabetic humans and animals. In diabetes, benfotiamine induces key thiamine
      dependent enzymes of the pentose shunt to reduce accumulation of toxic
      metabolites including advanced glycation end products (AGE). Related mechanisms
      may lead to reversal of plaque formation by benfotiamine in animals. If so, the
      use of benfotiamine could provide a safe intervention to reverse biological and
      clinical processes of AD progression. This article is part of a Special Issue
      entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

PMID- 22982065
TI  - A role of DNA-dependent protein kinase for the activation of AMP-activated
      protein kinase in response to glucose deprivation.
AB  - The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) plays an
      essential role in double-strand break repair by initially recognizing and binding
      to DNA breaks. Here, we show that DNA-PKcs interacts with the regulatory gamma1
      subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme that has
      been proposed to function as a "fuel gauge" to monitor changes in the energy
      status of cells and is controlled by the upstream kinases LKB1 and
      Ca2+/calmodulin-dependent kinase kinase (CaMKK). In co-immunoprecipitation
      analyses, DNA-PKcs and AMPKgamma1 interacted physically in DNA-PKcs-proficient
      M059K cells but not in DNA-PKcs-deficient M059J cells. Glucose deprivation
      stimulated phosphorylation of AMPKalpha on Thr172 and of acetyl-CoA carboxylase
      (ACC), a downstream target of AMPK, is substantially reduced in M059J cells
      compared with M059K cells. The inhibition or down-regulation of DNA-PKcs by the
      DNA-PKcs inhibitors, wortmannin and Nu7441, or by DNA-PKcs siRNA caused a marked
      reduction in AMPK phosphorylation, AMPK activity, and ACC phosphorylation in
      response to glucose depletion in M059K, WI38, and IMR90 cells. In addition, DNA
      DNA-PKcs(-/-) mouse embryonic fibroblasts (MEFs) exhibited decreased AMPK
      activation in response to glucose-free conditions. Furthermore, the knockdown of
      DNA-PKcs led to the suppression of AMPK (Thr172) phosphorylation in LKB1
      deficient HeLa cells under glucose deprivation. Taken together, these findings
      support the positive regulation of AMPK activation by DNA-PKcs under glucose
      deprived conditions in mammalian cells.

PMID- 22982066
TI  - Silver nanoparticles effects on epididymal sperm in rats.
AB  - The motivation of our study was to examine the acute effects of intravenously
      administered a single bolus dose of silver nanoparticles (AgNPs) on rat
      spermatogenesis and seminiferous tubules morphology. In the treated rats compared
      to the vehicle treated control animals, the experiments revealed a size-dependent
      (20nm and 200nm), dose-dependent (5 and 10mg/kg body mass) and time-dependent
      (24h, 7 and 28days) decrease the epididymal sperm count measured by histological
      methods. In parallel AgNPs injection increased the level of DNA damage in germ
      cells, as measured by alkaline comet assay. Histological examination of the
      testes showed change in the testes seminiferous tubule morphometry in 200nm Ag
      NPs treated rats. No change of body weight, adipose tissue distribution and the
      frequency of abnormal spermatozoa was observed. Twenty nanometers AgNP appeared
      to be more toxic than 200nm ones.

PMID- 22982064
TI  - Fibroblasts in post-infarction inflammation and cardiac repair.
AB  - Fibroblasts are the predominant cell type in the cardiac interstitium. As the
      main matrix-producing cells in the adult mammalian heart, fibroblasts maintain
      the integrity of the extracellular matrix network, thus preserving geometry and
      function. Following myocardial infarction fibroblasts undergo dynamic phenotypic
      alterations and direct the reparative response. Due to their strategic location,
      cardiac fibroblasts serve as sentinel cells that sense injury and activate the
      inflammasome secreting cytokines and chemokines. During the proliferative phase
      of healing, infarct fibroblasts undergo myofibroblast transdifferentiation
      forming stress fibers and expressing contractile proteins (such as alpha-smooth
      muscle actin). Mechanical stress, transforming growth factor (TGF)-beta/Smad3
      signaling and alterations in the composition of the extracellular matrix induce
      acquisition of the myofibroblast phenotype. In the highly cellular and growth
      factor-rich environment of the infarct, activated myofibroblasts produce matrix
      proteins, proteases and their inhibitors regulating matrix metabolism. As the
      infarct matures, "stress-shielding" of myofibroblasts by the cross-linked matrix
      and growth factor withdrawal may induce quiescence and ultimately cause apoptotic
      death. Because of their critical role in post-infarction cardiac remodeling,
      fibroblasts are promising therapeutic targets following myocardial infarction.
      However, the complexity of fibroblast functions and the pathophysiologic
      heterogeneity of post-infarction remodeling in the clinical context discourage
      oversimplified approaches in clinical translation. This article is part of a
      Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of
      Differentiation, Metabolism and Contraction.

PMID- 22982067
TI  - Tickling stimulation causes the up-regulation of the kallikrein family in the
      submandibular gland of the rat.
AB  - We recently showed that tactile stimulation (tickling) accompanied by positive
      emotion altered the expression of many genes in the rat hypothalamus (Hori et
      al., 2009 [15]). In this study, the effect of repeated tickling on gene
      expressions of the rat salivary gland was examined. After 4-week stimulation,
      several genes of the kallikrein (Klk) family were remarkably up-regulated and the
      alpha-amylase (amylase) gene was down-regulated in DNA microarray analysis. In
      quantitative analysis using real-time PCR of the submandibular gland of the rats
      tickled for 2 weeks, mRNAs of Klk1, Klk2 (Klk1c2, Tonin), Klk7 (Klk1l), Klk1b3
      (Nerve growth factor, gamma), Klk1c10, Klks3 (Klk1c9) and GK11 were significantly
      2-5-fold increased among 18 members of the Klk gene family examined and the
      submandibular amylase was decreased compared with the lightly touched and
      untouched control rats. In immunoblot analysis the increase in Klk7 protein was
      observed in the whole cell lysate fraction of the submandibular gland. In
      immunohistochemical analysis with anti-Klk7 polyclonal antibody, the immunostain
      was increased in duct cells of the submandibular gland of the tickled rat when
      compared with the lightly touched and untouched control rats. These results
      suggest that tactile sensory processing in the central nervous system affects the
      gene expression in the peripheral tissue probably via hormonal and/or autonomic
      neural activities. Submandibular Klks may be biochemical markers indicating
      positive emotional states.

PMID- 22982068
TI  - Differential responses to distinct psychotropic agents of selectively bred
      dominant and submissive animals.
AB  - Dominance and submissiveness are two opposite poles of behavior representing
      important functional elements in the development of social interactions. We
      previously demonstrated the inheritability of these traits by selective breeding
      based upon the dominant-submissive relationships (DSR) food competition paradigm.
      Continued multigenerational behavioral selection of Sabra mice yielded animal
      populations with strong and stable features of dominance and submissiveness. We
      found that these animals react differentially to stressogenic triggers,
      antidepressants and mood stabilizing agents. The anxiolytic compound diazepam
      (1.5mg/kg, i.p.) reduced anxiety-like behavior of submissive animals, but showed
      anxiogenic effects among dominant animals. In the Forced Swim test, the
      antidepressant paroxetine (1, 3 and 10mg/kg, i.p.) markedly reduced immobility of
      submissive animals, demonstrating antidepressant-like effect. In contrast, when
      administered to dominant animals, paroxetine caused extreme (frenetic) activity.
      The mood stabilizer lithium (0.4%, p.o.) selectively influenced dominant mice,
      without affecting the behavior of submissive animals. In summary, we describe
      here two distinct animal populations possessing strong dominant and submissive
      phenotypes. We suggest that these populations hold potential as tools for
      studying the molecular basis and pharmacogenetics of dominant and submissive
      behavior.

PMID- 22982069
TI  - Event-related potential correlates of emergent inference in human arbitrary
      relational learning.
AB  - Two experiments investigated the functional-anatomical correlates of cognition
      supporting untrained, emergent relational inference in a stimulus equivalence
      task. In Experiment 1, after learning a series of conditional relations involving
      words and pseudowords, participants performed a relatedness task during which EEG
      was recorded. Behavioural performance was faster and more accurate on untrained,
      indirectly related symmetry (i.e., learn AB and infer BA) and equivalence trials
      (i.e., learn AB and AC and infer CB) than on unrelated trials, regardless of
      whether or not a formal test for stimulus equivalence relations had been
      conducted. Consistent with previous results, event related potentials (ERPs)
      evoked by trained and emergent trials at parietal and occipital sites differed
      only for those participants who had not received a prior equivalence test.
      Experiment 2 further replicated and extended these behavioural and ERP findings
      using arbitrary symbols as stimuli and demonstrated time and frequency
      differences for trained and untrained relatedness trials. Overall, the findings
      demonstrate convincingly the ERP correlates of intra-experimentally established
      stimulus equivalence relations consisting entirely of arbitrary symbols and offer
      support for a contemporary cognitive-behavioural model of symbolic categorisation
      and relational inference.

PMID- 22982070
TI  - Development of home cage social behaviors in BALB/cJ vs. C57BL/6J mice.
AB  - BALB/cJ and C57BL/6J inbred mouse strains have been proposed as useful models of
      low and high levels of sociability (tendency to seek social interaction),
      respectively, based primarily on behaviors of ~30-day-old mice in the Social
      Approach Test (SAT). In the SAT, approach and sniffing behaviors of a test mouse
      toward an unfamiliar stimulus mouse are measured in a novel environment. However,
      it is unclear whether such results generalize to a familiar environment with a
      familiar social partner, such as with a littermate in a home cage environment. We
      hypothesized that C57BL/6J mice would show higher levels of social behaviors than
      BALB/cJ mice in the home cage environment, particularly at 30 days-of-age. We
      measured active and passive social behaviors in home cages by pairs of BALB/cJ or
      C57BL/6J littermates at ages 30, 41, and 69 days. The strains did not differ
      robustly in their active social behaviors. C57BL/6J mice were more passively
      social than BALB/cJ mice at 30 days, and C57BL/6J levels of passive social
      behaviors declined to BALB/cJ levels by 69 days. The differences in passive
      social behaviors at 30 days-of-age were primarily attributable to differences in
      huddling. These results indicate that different test conditions (SAT conditions
      vs. home cage conditions) elicit strain differences in distinct types of
      behaviors (approach/sniffing vs. huddling behaviors, respectively). Assessment of
      the more naturalistic social interactions in the familiar home cage environment
      with a familiar littermate will provide a useful component of a comprehensive
      assessment of social behaviors in mouse models relevant to autism.

PMID- 22982071
TI  - Acute ethanol intake induces superoxide anion generation and mitogen-activated
      protein kinase phosphorylation in rat aorta: a role for angiotensin type 1
      receptor.
AB  - Ethanol intake is associated with increase in blood pressure, through unknown
      mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative
      stress and induces vascular dysfunction through renin-angiotensin system (RAS)
      activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in
      male Wistar rats. The transient decrease in blood pressure induced by ethanol was
      not affected by the previous administration of losartan (10 mg/kg; p.o. gavage),
      a selective AT1 receptor antagonist. Acute ethanol intake increased plasma renin
      activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin
      I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and
      vascular oxidative stress, evidenced by increased plasma thiobarbituric acid
      reacting substances (TBARS) levels, NAD(P)H oxidase-mediated vascular generation
      of superoxide anion and p47phox translocation (cytosol to membrane). These
      effects were prevented by losartan. Isolated aortas from ethanol-treated rats
      displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited
      ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake
      decreased acetylcholine-induced relaxation and increased phenylephrine-induced
      contraction in endothelium-intact aortas. Ethanol significantly decreased plasma
      and aortic nitrate levels. These changes in vascular reactivity and in the end
      product of endogenous nitric oxide metabolism were not affected by losartan. Our
      study provides novel evidence that acute ethanol intake stimulates RAS activity
      and induces vascular oxidative stress and redox-signaling activation through AT1
      dependent mechanisms. These findings highlight the importance of RAS in acute
      ethanol-induced oxidative damage.

PMID- 22982072
TI  - In vivo corrosion, tumor outcome, and microarray gene expression for two types of
      muscle-implanted tungsten alloys.
AB  - Tungsten alloys are composed of tungsten microparticles embedded in a solid
      matrix of transition metals such as nickel, cobalt, or iron. To understand the
      toxicology of these alloys, male F344 rats were intramuscularly implanted with
      pellets of tungsten/nickel/cobalt, tungsten/nickel/iron, or pure tungsten, with
      tantalum pellets as a negative control. Between 6 and 12 months, aggressive
      rhabdomyosarcomas formed around tungsten/nickel/cobalt pellets, while those of
      tungsten/nickel/iron or pure tungsten did not cause cancers. Electron microscopy
      showed a progressive corrosion of the matrix phase of tungsten/nickel/cobalt
      pellets over 6 months, accompanied by high urinary concentrations of nickel and
      cobalt. In contrast, non-carcinogenic tungsten/nickel/iron pellets were minimally
      corroded and urinary metals were low; these pellets having developed a surface
      oxide layer in vivo that may have restricted the mobilization of carcinogenic
      nickel. Microarray analysis of tumors revealed large changes in gene expression
      compared with normal muscle, with biological processes involving the cell cycle
      significantly up-regulated and those involved with muscle development and
      differentiation significantly down-regulated. Top KEGG pathways disrupted were
      adherens junction, p53 signaling, and the cell cycle. Chromosomal enrichment
      analysis of genes showed a highly significant impact at cytoband 7q22 (chromosome
      7) which included mouse double minute (MDM2) and cyclin-dependant kinase (CDK4)
      as well as other genes associated with human sarcomas. In conclusion, the
      tumorigenic potential of implanted tungsten alloys is related to mobilization of
      carcinogenic metals nickel and cobalt from corroding pellets, while gene
      expression changes in the consequent tumors are similar to radiation induced
      animal sarcomas as well as sporadic human sarcomas.

PMID- 22982073
TI  - Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated
      proteins is responsible for the intestinal disposition and poor bioavailability
      of emodin.
AB  - Emodin is a poorly bioavailable but promising plant-derived anticancer drug
      candidate. The low oral bioavailability of emodin is due to its extensive
      glucuronidation in the intestine and liver. Caco-2 cell culture model was used to
      investigate the interplay between UDP-glucuronosyltransferases (UGTs) and efflux
      transporters in the intestinal disposition of emodin. Bidirectional transport
      assays of emodin at different concentrations were performed in the Caco-2
      monolayers with or without multidrug resistance-associated protein (MRP) and
      breast cancer resistance protein (BCRP) efflux transporter chemical inhibitors.
      The bidirectional permeability of emodin and its glucuronide in the Caco-2
      monolayers was determined. Emodin was rapidly metabolized to emodin glucuronide
      in Caco-2 cells. LTC4, a potent inhibitor of MRP2, decreased the efflux of emodin
      glucuronide and also substantially increased the intracellular glucuronide level
      in the basolateral-to-apical (B-A) direction. MK-571, chemical inhibitor of MRP2,
      MRP3, and MRP4, significantly reduced the efflux of glucuronide in the apical-to
      basolateral (A-B) and B-A directions in a dose-dependent manner. However,
      dipyridamole, a BCRP chemical inhibitor demonstrated no effect on formation and
      efflux of emodin glucuronide in Caco-2 cells. In conclusion, UGT is a main
      metabolic pathway for emodin in the intestine, and the MRP family is composed of
      major efflux transporters responsible for the excretion of emodin glucuronide in
      the intestine. The coupling of UGTs and MRP efflux transporters causes the
      extensive metabolism, excretion, and low bioavailability of emodin.

PMID- 22982074
TI  - Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid
      hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid
      receptors beta.
AB  - Several recent reports suggested that hydroxylated polybrominated diphenyl ethers
      (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural
      features for thyroid hormone activity of HO-PBDEs and the binding mode between HO
      PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO
      PBDEs to thyroid receptors beta was studied based on the combination of 3D-QSAR,
      molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor
      based 3D-QSAR models were obtained using Comparative Molecular Similarity Index
      Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded
      satisfactory statistical results: leave-one-out cross-validation correlation
      coefficient (q2) was 0.571 and non-cross-validation correlation coefficient (r2)
      was 0.951. Furthermore, the results of internal validation such as bootstrapping,
      leave-many-out cross-validation, and progressive scrambling as well as external
      validation indicated the rationality and good predictive ability of the best
      model. In addition, molecular docking elucidated the conformations of compounds
      and key amino acid residues at the docking pocket, MD simulation further
      determined the binding process and validated the rationality of docking results.

PMID- 22982075
TI  - Detection and genotyping of human papillomavirus by five assays according to
      cytologic results.
AB  - Five assays for the detection of human papillomavirus (HPV) with different assay
      principles were evaluated. A total of 230 cervical swab specimens were collected
      from subjects according to the cytologic results. All specimens were tested by
      the following assays: hybrid capture 2 (HC2), two real-time PCR assays (Abbott
      RealTime HR and AdvanSure RealTime), liquid beads microarray (GeneFinder) and
      peptide nucleic acid-based array (PANArray). The HPV DNA of 99 samples was
      sequenced to identify genotypes. Concordance rates between the results for the
      identification of 14 high risk HPV genotypes by any two of the evaluated assays,
      except for AdvanSure RealTime, ranged from 83.0% to 88.3%, and those for the
      identification of genotypes 16 and 18, except for HC2, were 93.0% and 96.1%,
      respectively. The results for the evaluation of high risk HPV genotypes by HC2
      agreed with those of the other assays in 76.5-86.5% of cases. Identification of
      HPV genotype by GeneFinder and PANArray corresponded with that by direct
      sequencing in 88.9% and 84.8% of sequenced samples. This study demonstrated that
      HC2 and the two real-time PCR assays could be used for routine HPV screening, and
      the other genotyping assays can be applied for epidemiologic surveillance.

PMID- 22982076
TI  - A strand specific real-time RT-PCR method for the targeted detection of the three
      species (vRNA, cRNA and mRNA) of infectious salmon anaemia virus (ISAV)
      replicative RNA.
AB  - Three species of viral-derived RNA (vRNA, cRNA and mRNA) are produced during an
      infectious salmon anaemia virus (ISAV) infection. Conventional real-time RT-PCR
      (RT-qPCR) targeting ISAV segment 8 provides a very sensitive method for the
      detection of ISAV RNA, however it does not differentiate between these three
      individual RNA species. In this study, strand-specific tagged primers have been
      utilised in the RT reaction to specifically produce cDNA corresponding to each of
      the 3 viral RNA types produced from ISAV segment 8 for the subsequent detection
      by real-time PCR. The RNA species-specific assay was successfully used to
      specifically distinguish synthetic T7-produced RNA transcripts representing the 3
      species of ISAV RNA at levels up to approximately 10(5)-fold higher than the
      other types. In addition, the method was applied to investigate the production of
      segment 8 RNA in time-course tissue culture experiments performed at optimal (15
      degrees C), sub-optimal (20 degrees C) and inadequate (25 degrees C) temperatures
      for replication or in the presence of a chemical inhibitor to vary the RNA
      populations and investigate its effectiveness. Variation in RNA production was
      observed between the optimal and sub-optimal temperatures and in the presence of
      the chemical inhibitor. Production of all RNA species was completely inhibited at
      25 degrees C indicating the potential usefulness of the assay as a tool in the
      understanding of ISAV replication and transcription dynamics.

PMID- 22982077
TI  - Lim mineralization protein is involved in the premature calvarial ossification in
      sporadic craniosynostoses.
AB  - Sporadic mono-sutural craniosynostosis represents a highly prevalent regional
      bone disorder, where a single cranial suture undergoes premature ossification due
      to a generally unclear etiopathogenesis. The LIM mineralization protein (LMP) was
      recently described as an efficient osteogenic molecule involved in osteoblast
      differentiation, expressed in calvarial tissues upon corticosteroid-osteogenic
      induction and used as a potent inducer of bone formation in several animal
      models. In this study, calvarial cells isolated from both prematurely fused and
      physiologically patent sutures of children with sporadic craniosynostosis, were
      used as an in vitro paradigmatic model for the study of the molecular events
      involved in calvarial osteogenesis, focusing on the possible role of the LMP
      related osteogenic signaling. Calvarial cells isolated from both patent and fused
      sutures expressed a mesenchymal-like immunophenotype. Cells isolated from fused
      sutures displayed an increased osteogenic potential, being able to undergo
      spontaneous mineralization and premature response to osteogenic induction,
      leading to in vitro bone nodule formation. The expression of LMP and its target
      genes (bone morphogenetic protein-2, osteocalcin and Runt-related transcription
      factor 2) was significantly up-regulated in cells derived from the fused sutures.
      Upon silencing the expression of LMP in fused suture-derived cells, the
      osteogenic potential along with the expression of osteo-specific transcription
      factors decreased, restoring the "physiologic" cell behavior. These results
      suggested that: 1. mesenchymal cells residing in fused sutures display a
      constitutionally active osteogenic disposition leading to the premature suture
      ossification; 2. the molecular basis of the overactive osteogenic process may at
      least in part involve a deregulation of the LMP-related pathway in calvarial
      cells.

PMID- 22982078
TI  - Delineating the 17q24.2-q24.3 microdeletion syndrome phenotype.
AB  - We present an 11-year-old girl with a 2.3 Mb de novo interstitial deletion in
      chromosome 17q24.2-q24.3 identified by array CGH. The phenotype in this case
      includes skeletal malformations (lower limb bowing, progressive scoliosis and
      dental abnormalities), feeding problems, mild learning difficulties, and a
      characteristic facial appearance. Much of the phenotype is attributable to the
      deletion of KCNJ2, which causes Andersen Tawil Syndrome (ATS), but the facial
      appearance is not typical. We hypothesise that the presence of mild channelopathy
      related features seen in ATS may be explained by haplo-insufficiency, leading to
      a reduced number of functionally normal Kir2.1 channels. Comparison is made to
      previous reports describing overlapping 17q deletions, and potential candidate
      genes which account for the specific phenotypic similarities with this case are
      highlighted.

PMID- 22982079
TI  - Beauveria brongniartii on white grubs attacking sugarcane in South Africa.
AB  - Beauveria brongniartii (Saccardo) Petch fungal infections were observed on the
      melolonthid Hypopholis sommeri Burmeister (Coleoptera: Scarabaeidae) at two sites
      (Harden Heights and Canema) in the sugarcane producing area of the northern
      KwaZulu-Natal Midlands of South Africa. To initially identify the disease-causing
      fungus, 17 different fluorescently-labelled microsatellite PCR primers were used
      to target 78 isolates of Beauveria spp. DNA. Microsatellite data resolved two
      distinct clusters of Beauveria isolates which represented the Beauveria bassiana
      s.s. (Balsamo) Vuillemin (17 isolates) and B. brongniartii (60 isolates) species
      groups. These groupings were supported by two gene regions, the nuclear ribosomal
      Internal Transcribed Spacer (ITS) and the nuclear Bloc gene of which 23 exemplar
      Beauveria isolates were represented and sequenced. When microsatellite data were
      analysed, 26 haplotypes among 58 isolates of B. brongniartii were distinguished.
      Relatively low levels of genetic diversity were detected in B. brongniartii and
      isolates were shown to be closely related. No genetic differentiation was
      observed between the Harden Heights and Canema populations; they thus may be
      considered one, structured and fragmented population over a distance of 5.5 km.
      Historically high levels of gene flow from swarming H. sommeri beetles is the
      proposed mechanism for this observed lack of genetic differentiation between
      populations. Microsatellite analyses also showed that B. brongniartii conidia
      were being cycled from arboreal forest to subterranean sugarcane habitats and
      vice versa in the environment by H. sommeri life stages. This is the first record
      of this species of fungus infecting H. sommeri larvae and adults in South Africa.

PMID- 22982080
TI  - The Buried in Treasures Workshop: waitlist control trial of facilitated support
      groups for hoarding.
AB  - Hoarding is a serious form of psychopathology that has been associated with
      significant health and safety concerns, as well as the source of social and
      economic burden (Tolin, Frost, Steketee, & Fitch, 2008; Tolin, Frost, Steketee,
      Gray, & Fitch, 2008). Recent developments in the treatment of hoarding have met
      with some success for both individual and group treatments. Nevertheless, the
      cost and limited accessibility of these treatments leave many hoarding sufferers
      without options for help. One alternative is support groups that require
      relatively few resources. Frost, Pekareva-Kochergina, and Maxner (2011) reported
      significant declines in hoarding symptoms following a non-professionally run 13
      week support group (The Buried in Treasures [BIT] Workshop). The BIT Workshop is
      a highly structured and short term support group. The present study extended
      these findings by reporting on the results of a waitlist control trial of the BIT
      Workshop. Significant declines in all hoarding symptom measures were observed
      compared to a waitlist control. The treatment response rate for the BIT Workshop
      was similar to that obtained by previous individual and group treatment studies,
      despite its shorter length and lack of a trained therapist. The BIT Workshop may
      be an effective adjunct to cognitive behavior therapy for hoarding disorder, or
      an alternative when cognitive behavior therapy is inaccessible.

PMID- 22982081
TI  - Passive coping response to depressive symptoms among low-income homebound older
      adults: does it affect depression severity and treatment outcome?
AB  - Due to their homebound state, lack of financial resources, and/or other life
      demands, a significant proportion of depressed, low-income homebound older adults
      experience depression. Because of their limited access to psychotherapy, most of
      these older adults self-manage their depressive symptoms. The purposes of this
      study were to examine (1) the relationship between homebound older adults' coping
      responses to depressed mood and the severity of their depressive symptoms at
      baseline (n = 121), and (2) the moderating effect of passive coping responses on
      the relationship between participation in problem-solving therapy (PST: in-person
      or telehealth delivery) and depressive symptoms at 12- and 24-week follow-ups.
      Controlling for the effects of demographic and disability characteristics,
      cognitive passive coping was significantly associated with baseline depressive
      symptoms, while behavioral passive coping was not. The main effect of baseline
      cognitive passive coping response was also significant in mixed-effects
      regression analysis, but the interaction between coping pattern and group was not
      significant. The results point to a possibility that cognitive passive copers may
      have benefited as much from PST as the rest of the PST participants. Further
      research needs to examine the moderating effect of coping responses to depressive
      symptoms on treatment efficacy of PST and other psychosocial interventions for
      late-life depression.

PMID- 22982082
TI  - A randomized controlled trial evaluating the efficacy of Triple P Online with
      parents of children with early-onset conduct problems.
AB  - OBJECTIVE: This study examined the efficacy of Triple P Online (TPOL), an eight
      module intensive online positive parenting program for parents of children with
      early-onset disruptive behavior problems. METHOD: One hundred and sixteen parents
      with 2-9-year-old children displaying early-onset disruptive behavior
      difficulties were randomly assigned to either the intervention condition (N = 60)
      or an internet-use-as-usual control group (N = 56). RESULTS: At post-intervention
      assessment, parents receiving the internet intervention TPOL had significantly
      better outcomes on measures of problem child behavior, dysfunctional parenting
      styles, parents' confidence in their parenting role, and parental anger. At 6
      month follow-up assessment intervention gains were generally maintained, and in
      some cases enhanced. Consumer satisfaction ratings for the program were high.
      CONCLUSIONS: Internet-delivered self-help parenting programs appear to make a
      valuable contribution to a comprehensive public health approach to parenting
      support.

PMID- 22982084
TI  - Investigating the effect of intolerance of uncertainty on catastrophic worrying
      and mood.
AB  - Intolerance of uncertainty (IU) is a construct known to influence catastrophic
      worry and is often observed in Generalized Anxiety Disorder (GAD). Research into
      the psychological manifestations of GAD suggests IU is associated with worry, but
      has not confirmed a causal link. The current study investigated the relationship
      between catastrophic worry and IU in a non-clinical undergraduate and
      postgraduate population (n = 46), with a mean age of 26.8 (SD = 5.52 years),
      where 71.74% were women. Participants received either a high or low IU
      manipulation, mood was measured throughout the study on 100 point visual analogue
      scales (VAS), and worry was measured using the catastrophising interview (CI).
      The high IU group generated significantly more catastrophising steps than the low
      IU group. Increased levels of sadness and anxiety were observed in the high as
      compared to the low IU group post IU manipulation, and this difference was
      maintained throughout the CI interview. A mediation analysis revealed that
      sadness and anxiety did not significantly mediate the relationship between IU and
      number of CI steps. These findings have implications for GAD treatment, as they
      suggest that manipulating IU affects measures of worry and its associated
      emotional and behavioural symptoms.

PMID- 22982085
TI  - The compensation and capitalization models: a test of two approaches to
      individualizing the treatment of depression.
AB  - Despite long-standing calls for the individualization of treatments for
      depression, modest progress has been made in this effort. The primary objective
      of this study was to test two competing approaches to personalizing cognitive
      behavioral treatment of depression (viz., capitalization and compensation).
      Thirty-four adults meeting criteria for Major Depressive Disorder (59% female,
      85% Caucasian) were randomized to 16-weeks of cognitive-behavioral treatment in
      which strategies used were selected based on either the capitalization approach
      (treatment matched to relative strengths) or the compensation approach (treatment
      matched to relative deficits). Outcome was assessed with a composite measure of
      both self-report (i.e., Beck Depression Inventory) and observer-rated (i.e.,
      Hamilton Rating Scale for Depression) depressive symptoms. Hierarchical linear
      modeling revealed a significant treatment approach by time interaction indicating
      a faster rate of symptom change for the capitalization approach compared to the
      compensation approach (d = .69, p = .03). Personalizing treatment to patients'
      relative strengths led to better outcome than treatment personalized to patients'
      relative deficits. If replicated, these findings would suggest a significant
      change in thinking about how therapists might best adapt cognitive-behavioral
      interventions for depression for particular patients.

PMID- 22982086
TI  - WITHDRAWN: Aminoglycoside phosphotransferase II gene as primary selection marker
      for Pichia pastoris producing full-length monoclonal antibody.
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- 22982083
TI  - Comparative effectiveness of CBT interventions for co-morbid chronic pain &
      insomnia: a pilot study.
AB  - INTRODUCTION: Chronic pain is difficult to treat and often precedes or
      exacerbates sleep disturbances such as insomnia. Insomnia, in turn, can amplify
      the pain experience. Both conditions are associated with inflammatory processes,
      which may be involved in the bi-directional relationship between pain and sleep.
      Cognitive behavioral therapy (CBT) for pain and CBT for insomnia are evidence
      based interventions for, respectively, chronic pain and insomnia. The study
      objectives were to determine the feasibility of combining CBT for pain and for
      insomnia and to assess the effects of the combined intervention and the stand
      alone interventions on pain, sleep, and mood outcomes compared to a control
      condition. METHODS: Twenty-one adults with co-occurring chronic pain and chronic
      insomnia were randomized to either CBT for pain, CBT for insomnia, combined CBT
      for pain and insomnia, or a wait-list control condition. RESULTS: The combined
      CBT intervention was feasible to deliver and produced significant improvements in
      sleep, disability from pain, depression and fatigue compared to the control
      condition. Overall, the combined intervention appeared to have a strong advantage
      over CBT for pain on most outcomes, modest advantage over both CBT for insomnia
      in reducing insomnia severity in chronic pain patients. DISCUSSION: CBT for pain
      and CBT for insomnia may be combined with good results for patients with co
      occurring chronic pain and insomnia.

PMID- 22982087
TI  - HSP27 expression in primary colorectal cancers is dependent on mutation of KRAS
      and PI3K/AKT activation status and is independent of TP53.
AB  - Colorectal adenomas display features of senescence, but these are often lost upon
      progression to carcinoma, indicating that oncogene induced senescence (OIS) could
      be a roadblock in colorectal cancer (CRC) development. Heat shock proteins (HSPs)
      have been implicated in the prognosis of CRC and HSP based therapy is a current
      interest for drug development. Recent cell culture studies have suggested that in
      the absence of a TP53 mutation, OIS mediated by PI3K/AKT activation can be
      circumvented by high expression of HSPs. Furthermore, while PI3K/AKT activation
      and KRAS mutations are independent inducers of OIS, PI3K/AKT activation can
      suppress KRAS-induced OIS when both are present in cultured cells. As KRAS
      mutations, PI3K/AKT activation and TP53 mutations are all common features of CRC,
      it is possible that the requirement for HSP to inhibit OIS in CRC is dependent on
      the mutation spectrum of a tumour. However, work on HSP that utilised mutation
      profiled human tumour tissues has been limited. Here, we characterised the
      expression of two major HSP proteins (HSP27 and 72) by immunohistochemistry
      (IHC), the mutation status of TP53, KRAS and PIK3CA genes by direct sequencing
      and the activation status of AKT by IHC in a cohort of unselected primary CRC
      (n=74). We compare our data with findings generated from cell-based studies.
      Expression of HSP27 and HSP72 was correlated to clinicopathological and survival
      data but no significant association was found. We also established the mutation
      status of TP53, KRAS and PIK3CA genes and the activation status of AKT in our CRC
      panel. We did not detect any associations between HSP27 or HSP72 expression with
      TP53 mutation status. However, HSP27 expression in CRCs was strongly associated
      with the co-presence of wildtype KRAS and activated PI3K/AKT (p=0.004),
      indicating a possible role of HSP27 in overcoming PI3K/AKT induced OIS in
      tumours. Our studies suggest a role for using archival tissues in validating
      hypotheses generated from cell culture based investigations.

PMID- 22982088
TI  - Primary and secondary metabolism regulates lipolysis in appressoria of
      Colletotrichum orbiculare.
AB  - The conidia of Colletotrichum orbiculare, the causal agent of cucumber
      anthracnose, develop appressoria that are pigmented with melanin for host plant
      infection. Premature appressoria contain abundant lipid droplets (LDs), but these
      disappear during appressorial maturation, indicating lipolysis inside the
      appressorial cells. The lipolysis and melanization in appressoria require the
      peroxin PEX6, suggesting the importance of peroxisomal metabolism in these
      processes. To investigate the relationships between appressorial lipolysis and
      fungal metabolic pathways, C. orbiculare knockout mutants of MFE1, which encodes
      a peroxisomal multifunctional enzyme, were generated in this study, and the
      phenotype of the mfe1 mutants was investigated. In contrast to the wild-type
      strain, which forms melanized appressoria, the mfe1 mutants formed colorless
      nonmelanized appressoria with abundant LDs, similar to those of pex6 mutants.
      This indicates that fatty acid beta-oxidation in peroxisomes is critical for the
      appressorial melanization and lipolysis of C. orbiculare. Soraphen A, a specific
      inhibitor of acetyl-CoA carboxylase, inhibited appressorial lipolysis and
      melanization, producing phenocopies of the mfe1 mutants. This suggests that the
      conversion of acetyl-CoA, derived from fatty acid beta-oxidation, to malonyl-CoA
      is required for the activation of lipolysis in appressoria. Surprisingly, we
      found that genetically blocking PKS1-dependent polyketide synthesis, an initial
      step in melanin biosynthesis, also impaired appressorial lipolysis. In contrast,
      genetically or pharmacologically blocking the steps in melanin synthesis
      downstream from PKS1 did not abolish appressorial lipolysis. These findings
      indicate that melanin biosynthesis, as well as fatty acid beta-oxidation, is
      involved in the regulation of lipolysis inside fungal infection structures.

PMID- 22982089
TI  - Cellular retinoic acid binding protein I mediates rapid non-canonical activation
      of ERK1/2 by all-trans retinoic acid.
AB  - All-trans retinoic acid (atRA), one of the active ingredients of vitamin A,
      exerts canonical activities to regulate gene expression mediated by nuclear RA
      receptors (RARs). AtRA could also elicit certain non-canonical activities
      including, mostly, rapid activation of extracellular signal regulated kinase 1/2
      (ERK1/2); but the mechanism was unclear. In this study, we have found that
      cellular retinoic acid binding protein I (CRABPI) mediates the non-canonical, RAR
      and membrane signal-independent activation of ERK1/2 by atRA in various cellular
      backgrounds. In the context of embryonic stem cells (ESCs), atRA/CRABPI-dependent
      ERK1/2 activation rapidly affects ESC cell cycle, specifically to expand the G1
      phase. This is mediated by ERK stimulation resulting in dephosphorylation of
      nuclear p27, which elevates nuclear p27 protein levels to block G1 progression to
      S phase. This is the first study to identify CRABPI as the mediator for non
      canonical activation of ERK1/2 by atRA, and demonstrate a new functional role for
      CRABPI in modulating ESC cell cycle progression.

PMID- 22982090
TI  - Upregulation of sestrin 2 expression via JNK pathway activation contributes to
      autophagy induction in cancer cells.
AB  - JNK signaling functions to induce defense mechanisms that protect organisms
      against a variety of different situations. The sestrin 2 gene, a p53-regulated
      member of the sestrins family, which lead to AMPK-dependent inhibition of TOR
      signaling, emerges as a novel player in autophagy induction. However, the
      relationship between JNK pathway, autophagy induction and sestrin 2 expression
      remains elusive. In the present study, we identify JNK as a regulator of
      autophagy in nasopharyngeal carcinoma cell lines CNE1 and CNE2 exposed to
      excisanin A or serum deprivation and demonstrate that activation of JNK can cause
      upregulation of sestrin 2 expression, which could be blocked by specific siRNAs
      directed against JNK1/2 or c-Jun. Chromatin immunoprecipitation and luciferase
      reporter analysis revealed that c-Jun was transcriptionally involved in the
      regulation of sestrin 2. Furthermore, knockdown of sestrin 2 by siRNAs similarly
      inhibited autophagy induction. Moreover, silencing the expression of autophagy
      related gene ATG5 or sestrin 2 significantly decreases cell death induced by
      excisanin A. Our results therefore identify JNK as a novel mediator of sestrin 2
      expression, which plays a key role in autophagy induction following anticancer
      therapies in cancers.

PMID- 22982091
TI  - Advanced glycation end products and lipofuscin deposits share the same location
      in cardiocytes of the failing heart.
AB  - BACKGROUND: Disturbed glucose metabolism, particularly in diabetes type 2 (DM2),
      may result in advanced glycation end product (AGE) formation. One of the possible
      targets for this reaction is lipofuscin (LF), an intracytoplasmic garbage
      presumed to be a marker of physiologic and preterm aging of cells. The study was
      performed to seek for a relationship between AGE and LF in cardiocytes of the
      failing hearts. MATERIAL AND METHODS: Archived tissue samples from 136 hearts
      explanted before transplantation (in 14 pts. with ischemic cardiomyopathy (CM)
      and DM2; 8 pts. with dilated CM and DM2; 67 non-diabetic pts. with ischemic CM;
      47 non-diabetic pts. with dilated CM), 14 autopsy cases with DM2, and 20 heart
      donors (control group) were involved in the study. Immunohistochemical
      localization of AGE was applied. The coexistence of lipofuscin and AGE was
      studied by LF autofluorescence in AGE-positive slides. RESULTS: LF granules
      inside AGE deposits were present in all studied groups with varying frequencies,
      but the differences were non-significant. LF granules joined significantly with
      dispersed patterns of AGE i.e. diffuse and mixed, whereas coincidence of LF and
      AGE forming granular pattern was rare. CONCLUSIONS: We demonstrate that LF may
      belong to the components of the AGE deposits. The frequency of this phenomenon is
      dependent on the AGE dispersion grade, but neither on diabetes nor cardiomyopathy
      presence.

PMID- 22982092
TI  - An amino acid substitution in Fasciola hepatica P-glycoprotein from
      triclabendazole-resistant and triclabendazole-susceptible populations.
AB  - Control of fasciolosis is threatened by the development of anthelmintic
      resistance. Enhanced triclabendazole (TCBZ) efflux by ABC transporters such as P
      glycoprotein (Pgp) has been implicated in this process. A putative full length
      cDNA coding for a Pgp expressed in adult Fasciola hepatica has been constructed
      and used to design a primer set capable of amplifying a region encoding part of
      the second nucleotide binding domain of Pgp when genomic DNA was used as a
      template. Application of this primer set to genomic DNA from TCBZ-resistant and 
      susceptible field populations has shown a significant difference in the alleles
      present. Analysis of an allele occurring at a three-fold higher frequency in the
      "resistant" population revealed that it was characterised by a serine to arginine
      substitution at residue 1144. Homology modelling studies have been used to locate
      this site in the Pgp structure and hence assess its potential to modify
      functional activity.

PMID- 22982093
TI  - Human gait recognition via deterministic learning.
AB  - Recognition of temporal/dynamical patterns is among the most difficult pattern
      recognition tasks. Human gait recognition is a typical difficulty in the area of
      dynamical pattern recognition. It classifies and identifies individuals by their
      time-varying gait signature data. Recently, a new dynamical pattern recognition
      method based on deterministic learning theory was presented, in which a time
      varying dynamical pattern can be effectively represented in a time-invariant
      manner and can be rapidly recognized. In this paper, we present a new model-based
      approach for human gait recognition via the aforementioned method, specifically
      for recognizing people by gait. The approach consists of two phases: a training
      (learning) phase and a test (recognition) phase. In the training phase, side
      silhouette lower limb joint angles and angular velocities are selected as gait
      features. A five-link biped model for human gait locomotion is employed to
      demonstrate that functions containing joint angle and angular velocity state
      vectors characterize the gait system dynamics. Due to the quasi-periodic and
      symmetrical characteristics of human gait, the gait system dynamics can be
      simplified to be described by functions of joint angles and angular velocities of
      one side of the human body, thus the feature dimension is effectively reduced.
      Locally-accurate identification of the gait system dynamics is achieved by using
      radial basis function (RBF) neural networks (NNs) through deterministic learning.
      The obtained knowledge of the approximated gait system dynamics is stored in
      constant RBF networks. A gait signature is then derived from the extracted gait
      system dynamics along the phase portrait of joint angles versus angular
      velocities. A bank of estimators is constructed using constant RBF networks to
      represent the training gait patterns. In the test phase, by comparing the set of
      estimators with the test gait pattern, a set of recognition errors are generated,
      and the average L(1) norms of the errors are taken as the similarity measure
      between the dynamics of the training gait patterns and the dynamics of the test
      gait pattern. Therefore, the test gait pattern similar to one of the training
      gait patterns can be rapidly recognized according to the smallest error
      principle. Finally, experiments are carried out on the NLPR and UCSD gait
      databases to demonstrate the effectiveness of the proposed approach.

PMID- 22982094
TI  - Exponential state estimation for Markovian jumping neural networks with time
      varying discrete and distributed delays.
AB  - This paper is concerned with the exponential state estimation for Markovian
      jumping neural networks with time-varying discrete and distributed delays. The
      parameters of the neural networks are subject to the switching from one mode to
      another according to a Markov chain. By constructing a novel Lyapunov-Krasovskii
      functional and developing a new convex combination technique, a new delay
      dependent exponential stability condition is proposed, such that for all
      admissible delay bounds, the resulting estimation error system is mean-square
      exponentially stable with a prescribed noise attenuation level in the H(infinity)
      sense. It is also shown that the design of the desired state estimator is
      achieved by solving a set of linear matrix inequalities (LMIs). The obtained
      condition implicitly establishes the relations among the maximum delay bounds,
      H(infinity) noise attenuation level and the exponential decay rate of the
      estimation error system. Finally, a numerical example is given to show the
      effectiveness of the proposed result.

PMID- 22982095
TI  - Annual incidence of hepatocellular carcinoma among patients with alcoholic
      cirrhosis and identification of risk groups.
AB  - BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) and associated
      risk factors in patients with alcoholic cirrhosis are not well defined.
      Surveillance for HCC among patients with cirrhosis who do not have hepatitis B is
      cost effective only if the expected risk of HCC exceeds 1.5% per year. We
      performed a prospective study to determine the incidence of HCC among patients
      with alcoholic cirrhosis and to identify risk factors. METHODS: We analyzed data
      from a surveillance program of 450 patients, aged 40 to 75 years, with alcoholic
      cirrhosis of Child-Pugh class A or B; patients were enrolled at the liver unit of
      a tertiary center from September 1992 through March 2010. Data were collected on
      20 demographic, clinical, and laboratory variables at the start of the study.
      Patients were examined every 3 to 6 months for 5 years to identify risk factors
      for HCC; incidence was determined from a median follow-up time of 42 months.
      RESULTS: Over the follow-up period, 62 patients developed HCC (43 in the first 5
      y of follow-up evaluation), with an annual incidence of 2.6%. By using
      multivariate analysis, age 55 years and older (hazard ratio, 2.39; 95% confidence
      interval, 1.27-4.51) and platelet counts less than 125 * 10(3)/mm(3) (hazard
      ratio, 3.29; 95% confidence interval, 1.39-7.85) were associated independently
      with the development of HCC. These variables were used to define 3 risk groups.
      The annual incidence of HCC in the group without either of these factors was 0.3%
      (n = 93), the annual incidence with 1 factor was 2.6% (n = 228), and the annual
      incidence with both factors was 4.8% (n = 129) (P < .0001). CONCLUSIONS: The
      annual incidence of HCC among patients with alcoholic cirrhosis of Child-Pugh
      class A or B is around 2.5%. Age and platelet count can be used to classify the
      patients in 3 different risk groups for HCC development within the next 5 years.

PMID- 22982097
TI  - Effects of birth cohort on long-term trends in mortality from colorectal cancer.
AB  - BACKGROUND & AIMS: The decrease in mortality from colorectal cancer might have
      begun before widespread use of screening colonoscopy and sigmoidoscopy
      examinations. We examined long-term time trends in colorectal cancer mortality in
      6 European countries to determine when the reduction began. METHODS: We analyzed
      mortality data from the national statistical offices of the United Kingdom
      (England and Wales), France, Italy, The Netherlands, Sweden, and Switzerland
      during the past 66 to 107 years. The data were made available by the national
      statistical offices of the 6 countries. Age-specific rates of death were plotted
      against the period of death, as period-age contours, and against the period of
      birth, as cohort-age contours. RESULTS: Long-term time trends in mortality from
      cancers of the rectum and colon each increased among generations born from 1800
      to 1880, and then decreased among all subsequent generations, in all 6 countries
      analyzed. Similar temporal patterns also were observed when data from men and
      women were analyzed separately. The birth cohort patterns of colorectal cancer
      mortality resemble those of gastric cancer and peptic ulcer. CONCLUSIONS: Time
      trends of mortality from colorectal cancer, in 6 European countries, are
      associated with birth cohort patterns: colorectal cancer mortality decreased
      among all generations since 1880. These patterns indicate that in addition to the
      use of screening colonoscopy, other factors, such as changes in Helicobacter
      pylori infection, may have affected mortality.

PMID- 22982096
TI  - Statins and colorectal cancer.
AB  - The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, more commonly
      referred to as statins, comprise a family of lipid-lowering drugs that are
      prescribed on a global scale on account of their proven safety and efficacy in
      reducing mortality from cardiovascular disease. Beyond their potent pharmacologic
      inhibition of cholesterol biosynthesis, statins appear to have pleiotropic
      effects, including modulation of cell growth, apoptosis, and inflammation.
      Through modulation of these pathways, statins have the potential to influence a
      wide range of disease processes, including cancer. Much attention has focused on
      the association between statins and colorectal cancer, raising the prospect that
      these well-tolerated compounds could form the basis of future chemopreventive
      strategies. Herein, we review the epidemiologic, clinical, and preclinical data
      relevant to statins and colorectal neoplasia, and discuss the current status and
      future potential of statins as chemopreventive agents.

PMID- 22982098
TI  - Porphyria cutanea tarda: treatment options revisited.

PMID- 22982099
TI  - Systemic sclerosis in small bowel.

PMID- 22982101
TI  - Management of belching, hiccups, and aerophagia.
AB  - Although belching and hiccups are regarded as normal behaviors, they can occur at
      high frequency or become persistent, becoming bothersome and requiring medical
      care. Patients with excessive belching frequently have supragastric belches.
      Excessive belching should be treated as a behavioral disorder. Persistent
      hiccups, however, can be the first presentation of a serious disorder that
      requires extensive diagnostic testing. When no cause is found, only the symptoms
      can be treated. Aerophagia is an episodic or chronic disorder in which patients
      (children and adults) swallow large quantities of air, which accumulate in the
      gastrointestinal tract to cause abdominal distention and bloating. These patients
      should not undergo explorative laparotomy because they do not have ileus. New
      treatment approaches are needed for patients with aerophagia.

PMID- 22982100
TI  - Classification, diagnosis, and management of cholangiocarcinoma.
AB  - Cholangiocarcinomas (CCAs) are tumors that develop along the biliary tract.
      Depending on their site of origin, they have different features and require
      specific treatments. Classification of CCAs into intrahepatic, perihilar, and
      distal subgroups has helped standardize the registration, treatment, and study of
      this lethal malignancy. Physicians should remain aware that cirrhosis and viral
      hepatitis B and C are predisposing conditions for intrahepatic CCA. Treatment
      options under development include locoregional therapies and a chemotherapy
      regimen of gemcitabine and cisplatin. It is a challenge to diagnose perihilar
      CCA, but an advanced cytologic technique of fluorescence in situ hybridization
      for polysomy can aid in diagnosis. It is important to increase our understanding
      of the use of biliary stents and liver transplantation in the management of
      perihilar CCA, as well as to distinguish distal CCAs from pancreatic cancer,
      because of different outcomes from surgery. We review advances in the
      classification, diagnosis, and staging of CCA, along with treatment options.

PMID- 22982102
TI  - A multiblock PLS model of cortico-cortical and corticomuscular interactions in
      Parkinson's disease.
AB  - Electroencephalography (EEG) and simultaneously-recorded electromyography (EMG)
      data are a means to assess integrity of the functional connection between the
      cortex and the muscle during movement. EEG-EMG coupling is typically assessed
      with pair-wise squared coherence, resulting in a small, but statistically
      significant coherence between a single EEG and a single EMG channel. However, a
      means to combine results across subjects is not straightforward with this
      approach because the exact frequency of maximal EEG-EMG coupling may vary between
      individuals, and it emphasizes the role of an individual locus in the brain in
      driving the muscle activity, when interactions between head regions may in fact
      be more influential on ongoing EMG activity. To deal with these issues, we
      implemented a multiblock Partial Least Squares (mbPLS) procedure, previously
      proposed in chemical applications, which incorporates a hierarchical structure
      into the ordinary two-block PLS often used in neuroimaging studies. In the
      current implementation, each subject's data features are collected in individual
      data blocks on a sub-level, while simultaneously aggregating the sub-level
      information to obtain a super-level group "consensus". We further extended the
      mbPLS model to include 3-dimensional matrices: time-frequency-EEG channel and a
      time-frequency-connection utilizing Partial Directed Coherence (PDC). We applied
      the proposed method to concurrent EEG and EMG data collected from ten normal
      subjects and nine patients with mild-moderate Parkinson's disease (PD) performing
      a dynamic motor task-that of sinusoidal squeezing. The results demonstrate that
      connections between EEG electrodes, rather than activity at individual
      electrodes, correspond more closely to ongoing EMG activity. In PD subjects,
      there was enhanced connectivity to and from occipital regions, likely related to
      the previously-described enhanced use of visual information during motor
      performance in this group. The proposed mbPLS framework is a promising technique
      for performing multi-subject, multi-modal data analysis and it allows for robust
      group inferences even in the face of large inter-subject variability.

PMID- 22982103
TI  - Articulatory movements modulate auditory responses to speech.
AB  - Production of actions is highly dependent on concurrent sensory information. In
      speech production, for example, movement of the articulators is guided by both
      auditory and somatosensory input. It has been demonstrated in non-human primates
      that self-produced vocalizations and those of others are differentially processed
      in the temporal cortex. The aim of the current study was to investigate how
      auditory and motor responses differ for self-produced and externally produced
      speech. Using functional neuroimaging, subjects were asked to produce sentences
      aloud, to silently mouth while listening to a different speaker producing the
      same sentence, to passively listen to sentences being read aloud, or to read
      sentences silently. We show that that separate regions of the superior temporal
      cortex display distinct response profiles to speaking aloud, mouthing while
      listening, and passive listening. Responses in anterior superior temporal
      cortices in both hemispheres are greater for passive listening compared with both
      mouthing while listening, and speaking aloud. This is the first demonstration
      that articulation, whether or not it has auditory consequences, modulates
      responses of the dorsolateral temporal cortex. In contrast posterior regions of
      the superior temporal cortex are recruited during both articulation conditions.
      In dorsal regions of the posterior superior temporal gyrus, responses to mouthing
      and reading aloud were equivalent, and in more ventral posterior superior
      temporal sulcus, responses were greater for reading aloud compared with mouthing
      while listening. These data demonstrate an anterior-posterior division of
      superior temporal regions where anterior fields are suppressed during motor
      output, potentially for the purpose of enhanced detection of the speech of
      others. We suggest posterior fields are engaged in auditory processing for the
      guidance of articulation by auditory information.

PMID- 22982104
TI  - Nonparametric inference of the hemodynamic response using multi-subject fMRI
      data.
AB  - Estimation and inferences for the hemodynamic response functions (HRF) using
      multi-subject fMRI data are considered. Within the context of the General Linear
      Model, two new nonparametric estimators for the HRF are proposed. The first is a
      kernel-smoothed estimator, which is used to construct hypothesis tests on the
      entire HRF curve, in contrast to only summaries of the curve as in most existing
      tests. To cope with the inherent large data variance, we introduce a second
      approach which imposes Tikhonov regularization on the kernel-smoothed estimator.
      An additional bias-correction step, which uses multi-subject averaged
      information, is introduced to further improve efficiency and reduce the bias in
      estimation for individual HRFs. By utilizing the common properties of brain
      activity shared across subjects, this is the main improvement over the standard
      methods where each subject's data is usually analyzed independently. A fast
      algorithm is also developed to select the optimal regularization and smoothing
      parameters. The proposed methods are compared with several existing
      regularization methods through simulations. The methods are illustrated by an
      application to the fMRI data collected under a psychology design employing the
      Monetary Incentive Delay (MID) task.

PMID- 22982105
TI  - Identification of gene pathways implicated in Alzheimer's disease using
      longitudinal imaging phenotypes with sparse regression.
AB  - We present a new method for the detection of gene pathways associated with a
      multivariate quantitative trait, and use it to identify causal pathways
      associated with an imaging endophenotype characteristic of longitudinal
      structural change in the brains of patients with Alzheimer's disease (AD). Our
      method, known as pathways sparse reduced-rank regression (PsRRR), uses group
      lasso penalised regression to jointly model the effects of genome-wide single
      nucleotide polymorphisms (SNPs), grouped into functional pathways using prior
      knowledge of gene-gene interactions. Pathways are ranked in order of importance
      using a resampling strategy that exploits finite sample variability. Our
      application study uses whole genome scans and MR images from 99 probable AD
      patients and 164 healthy elderly controls in the Alzheimer's Disease Neuroimaging
      Initiative (ADNI) database. 66,182 SNPs are mapped to 185 gene pathways from the
      KEGG pathway database. Voxel-wise imaging signatures characteristic of AD are
      obtained by analysing 3D patterns of structural change at 6, 12 and 24 months
      relative to baseline. High-ranking, AD endophenotype-associated pathways in our
      study include those describing insulin signalling, vascular smooth muscle
      contraction and focal adhesion. All of these have been previously implicated in
      AD biology. In a secondary analysis, we investigate SNPs and genes that may be
      driving pathway selection. High ranking genes include a number previously linked
      in gene expression studies to beta-amyloid plaque formation in the AD brain
      (PIK3R3,PIK3CG,PRKCAandPRKCB), and to AD related changes in hippocampal gene
      expression (ADCY2, ACTN1, ACACA, and GNAI1). Other high ranking previously
      validated AD endophenotype-related genes include CR1, TOMM40 and APOE.

PMID- 22982106
TI  - Distribution of protocadherin 9 protein in the developing mouse nervous system.
AB  - Protocadherin 9 (Pcdh9) is a member of the protocadherin family, which includes
      many members involved in various phenomena, such as cell-cell adhesion, neural
      projection, and synapse formation. Here, we identified Pcdh9 protein in the mouse
      brain and examined its distribution during neural development. Pcdh9, with a
      molecular weight of approximately 180 kDa, was localized at cell-cell contact
      sites in COS-1 cells transfected with Pcdh9 cDNA. In cultured neurons, it was
      detected at the growth cone and at adhesion sites along neurites. In the E13.5
      brain, prominent Pcdh9 immunoreactivity was detected in the dorsal thalamus along
      with other regions including the vestibulocochlear nerve. As development
      proceeded (E15.5-P1), Pcdh9 immunoreactivity became observable in various brain
      regions but was restricted to certain fiber tracts and brain nuclei.
      Interestingly, many Pcdh9-positive brain nuclei and fascicles belonged to the
      vestibular (e.g. vestibulocochlear nerve, vestibular nuclei, and the
      vestibulocerebellum) and oculomotor systems (medial longitudinal fascicles,
      oculomotor nucleus, trochlear nucleus, and interstitial nucleus of Cajal). In
      addition, we examined the distribution of Pcdh9 protein in the olfactory bulb,
      retina, spinal cord, and dorsal root ganglion. In these regions, Pcdh9 and OL
      protocadherin proteins were differentially distributed, with the difference
      highlighted in the olfactory bulb, where they were enriched in different subsets
      of glomeruli. In the mature retina, Pcdh9 immunoreactivity was detected in
      distinct sublaminae of the inner and outer plexiform layers. In the dorsal root
      ganglion, only certain subsets of neurons showed Pcdh9 immunoreactivity. These
      results suggest that Pcdh9 might be involved in formation of specific neural
      circuits during neural development.

PMID- 22982107
TI  - Cytoprotective effect of the small GTPase RhoB expressed upon treatment of
      fibroblasts with the Ras-glucosylating Clostridium sordellii lethal toxin.
AB  - Mono-glucosylation of (H/K/N)Ras by Clostridium sordellii lethal toxin (TcsL)
      blocks critical survival signaling pathways, resulting in apoptosis. In this
      study, TcsL and K-Ras knock-down by siRNA are presented to result in expression
      of the cell death-regulating small GTPase RhoB. TcsL-induced RhoB expression is
      based on transcriptional activation involving p38(alpha) MAP kinase. Newly
      synthesized RhoB protein is rapidly degraded in a proteasome- and a caspase
      dependent manner, providing first evidence for caspase-dependent degradation of a
      Rho family protein. Although often characterised as a pro-apoptotic protein, RhoB
      suppresses caspase-3 activation in TcsL-treated fibroblasts. The finding on the
      cytoprotective activity of RhoB in TcsL-treated cells re-enforces the concept
      that RhoB exhibits cytoprotective rather than pro-apoptotic activity in a
      cellular background of inactive Ras.

PMID- 22982108
TI  - Glycine decarboxylase controls photosynthesis and plant growth.
AB  - Photorespiration makes oxygenic photosynthesis possible by scavenging 2
      phosphoglycolate. Hence, compromising photorespiration impairs photosynthesis. We
      examined whether facilitating photorespiratory carbon flow in turn accelerates
      photosynthesis and found that overexpression of the H-protein of glycine
      decarboxylase indeed considerably enhanced net-photosynthesis and growth of
      Arabidopsis thaliana. At the molecular level, lower glycine levels confirmed
      elevated GDC activity in vivo, and lower levels of the CO(2) acceptor ribulose
      1,5-bisphosphate indicated higher drain from CO(2) fixation. Thus, the
      photorespiratory enzyme glycine decarboxylase appears as an important feed-back
      signaller that contributes to the control of the Calvin-Benson cycle and hence
      carbon flow through both photosynthesis and photorespiration.

PMID- 22982109
TI  - Inhibition of a cold-active alkaline phosphatase by imipenem revealed by in
      silico modeling of metallo-beta-lactamase active sites.
AB  - We demonstrate the inhibition of the native phosphatase activity of a cold active
      alkaline phosphatase from Vibrio (VAP) (IC(50) of 44+/-4 (n=4)MUM at pH 7.0 after
      a 30min preincubation) by a specific beta-lactam compound (only by imipenem, and
      not by ertapenem, meropenem, ampicillin or penicillin G). The homologous scaffold
      was detected by an in silico analysis that established the spatial and
      electrostatic congruence of the active site of a Class B2 CphA metallo-beta
      lactamase from Aeromonas hydrophila to the active site of VAP. The tested beta
      lactam compounds did not inhibit Escherichia coli or shrimp alkaline phosphatase,
      which could be ascribed to the lower congruence indicated by CLASP. There was no
      discernible beta-lactamase activity in the tested alkaline phosphatases. This is
      the first time a scaffold recognizing imipenem in an alkaline phosphatase (VAP)
      has been demonstrated.

PMID- 22982110
TI  - Synthetic rates of key stored fatty acids in the biosynthesis of sex pheromone in
      the moth Heliothis virescens.
AB  - Using a tracer-tracee approach, we fed 1-d-old virgin Heliothis virescens U-(13)C
      glucose and analyzed the key labeled fatty acids, (Z)-11-hexadecenoate,
      hexadecanoate and octadecanoate, known to be intermediates in pheromone
      biosynthesis, by mass isotopomer distribution analysis. This method allowed
      determination of enrichment, and fractional (FSR) and absolute (ASR) synthetic
      rates. As expected, FSRs and ASRs for all three moieties were greater in the
      scotophase than photophase. However, in whole gland extracts, FSRs and ASRs of
      (Z)-11-hexadecenoate and hexadecanoate were much lower than those of the major
      pheromone component, (Z)-11-hexadecenal, determined previously. Since pheromone
      is made via these acids, we postulated that pheromone was produced directly and
      very rapidly via a small pool of acyl CoA thioesters of these acids and that the
      pool of acids we analyzed in our whole gland extract was largely a 'dead end'
      pool of excess acids (i.e., not converted directly to pheromone) stored in
      glycerolipids. We tested this by fractionating the whole glandular extract and
      analyzing the glycerolipid fraction. FSRs and ASRs for the two acids in the
      glycerolipid fraction were similar to those for the whole gland extract,
      confirming our postulate. Thus, most acetate produced in the pheromone gland is
      converted rapidly and directly to pheromone, while excess fatty acids are stored
      in glycerolipids and remain relatively inaccessible for pheromone production, at
      least over the two periods studied. Precursor enrichment of octadecanoate was
      substantially lower than that determined for the two 16-carbon acids and
      pheromone component. This suggests that hexadecanoate is the principal product of
      the multi-enzyme complex fatty acid synthase in the gland, and that octadecanoate
      is formed by subsequent chain elongation of hexadecanoate.

PMID- 22982111
TI  - Discovery of potential bladder cancer biomarkers by comparative urine proteomics
      and analysis.
AB  - OBJECTIVE: We searched for bladder tumor markers by analyzing urine samples from
      patients with bladder cancer and from normal controls. METHODS: Proteins in urine
      samples of patients with bladder cancer and with normal controls were
      systematically examined by 2-dimensional electrophoresis combined with matrix
      assisted laser desorption ionization time-of-flight mass spectrometry. The
      expression of the protein apolipoprotein A-I (apoA-I) was confirmed by Western
      blot analysis and further evaluated. RESULTS: We successfully obtained the 2
      dimensional electrophoresis gel maps of urinary proteins in patients with bladder
      cancer and in normal controls. Thirty differentially expressed protein spots were
      successfully matched by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry. Combined with the SWISS-PROT database, only 14 proteins
      (beta-2-microglobulin, fatty acid-binding protein adipocyte, gelsolin, isoform 1
      of gelsolin, myoglobin, isoform 2 of fibrinogen alpha chain, apoA-I,
      prostaglandin D(2) synthase 21 kDa [brain], protein AMBP, transthyretin, keratin
      type II cytoskeletal 1, type II cytoskeletal 8, putative uncharacterized protein
      ALB, putative uncharacterized protein MASP2 [fragment]) were identified,
      including 2 putative proteins. Furthermore, apoA-I was confirmed by Western blot
      analysis, and the high level of apoA-I was found in urine samples from patients
      with bladder tumors compared with normal controls. CONCLUSIONS: Analysis of
      urinary proteome may be a feasible, noninvasive, and efficient strategy for
      searching for potential bladder tumor biomarkers. A significant relationship of
      expressed apoA-I was established between bladder cancer and normal controls. We
      concluded that 14 differential spots included the apoA-I and would be potential
      urinary biomarkers for the diagnosis and surveillance of bladder cancer.

PMID- 22982112
TI  - Nucleic acid delivery: roles in biogerontological interventions.
AB  - Prolongation of longevity is a history-long desire of humans. Driven by the
      genetic contribution to longevity and the remarkable plasticity of healthy
      lifespan as demonstrated in animal models, arduous efforts have been directed to
      aging and longevity research over the years. Today, our understanding of lifespan
      determination is much greater than it was in the past, but administrable
      interventions for longevity enhancement are still virtually absent. The aim of
      this article is to highlight the technical gap between basic biogerontological
      research and intervention development, and to explore the importance of nucleic
      acid (NA) delivery technologies in bridging the gap. It is hoped that this
      article can engender more awareness of the roles of NA delivery technologies in
      biogerontological interventions, particularly NA therapy.

PMID- 22982113
TI  - Occlusal adjustment associated with periodontal therapy--a systematic review.
AB  - OBJECTIVES: Occlusal adjustment as part of periodontal therapy has been
      controversial for years, mostly because the literature does not provide enough
      evidence regarding the influence of trauma from occlusion (TfO) on periodontitis.
      The need for occlusal adjustment in periodontal therapy is considered uncertain
      and requires investigation. The aim of this systematic review was to identify and
      analyse those studies that investigated the effects of occlusal adjustment,
      associated with periodontal therapy, on periodontal parameters. DATA: A protocol
      was developed that included all aspects of a systematic review: search strategy,
      selection criteria, selection methods, data collection and data extraction.
      SOURCES: A literature search was conducted using MEDLINE via PubMed, the Cochrane
      Central Register of Controlled Trials, and EMBASE. STUDY SELECTION: Three
      reviewers screened the titles and abstracts of articles according to the
      established criteria. Every article that indicated a possible match, or could not
      be excluded based on the information given in the title or abstract, was
      considered and evaluated. On final selection, four articles were included.
      CONCLUSIONS: Although the selected studies suggest an association between
      occlusal adjustment and an improvement in periodontal parameters, their
      methodological issues (explored in this review) suggest the need for new trials
      of a higher quality. There is insufficient evidence at present to presume that
      occlusal adjustment is necessary to reduce the progression of periodontal
      disease. CLINICAL SIGNIFICANCE: Although it is still not possible to determine
      the role of occlusal adjustment in periodontal treatment, adverse effects have
      not been related to occlusal adjustment. This means that the decision made by
      clinicians whether or not to use occlusal adjustment in conjunction with
      periodontal therapy hinges upon clinical evaluation, patient comfort, and tooth
      function.

PMID- 22982114
TI  - Reduced CD26 expression is associated with improved cardiac function after acute
      myocardial infarction: insights from the REPERATOR study.
AB  - Peripheral blood mononuclear cells (MNC) enhance cardiac recovery and repair
      after myocardial infarction (MI). The SDF-1alpha/CXCR4 axis plays a major role in
      cell homing to infarcted myocardium and is negatively regulated by CD26.
      Therefore, we studied the expression of CD26 during MI and its effects on cardiac
      function. Blood samples from forty-two patients who underwent a primary
      percutaneous coronary intervention (PCI) for a first ST-elevated MI were
      collected during primary PCI, 1 week and 3 months after MI. Soluble CD26 (sCD26)
      and membrane bound CD26 expression on MNCs (mncCD26) were determined. Left
      ventricular function and infarct size were measured within 1 day, 1 week and 3
      months follow up by magnetic resonance imaging. One week post MI, sCD26 was down
      regulated compared to baseline, while mncCD26 was higher at baseline and 1 week
      compared to 3 months. Increased mncCD26 expression at 1 week after MI was
      associated with decreased overall recovery of left ventricular function as
      measured by left ventricular end systolic volume index. Furthermore, the in vitro
      migration capacity of MNCs to SDF-1alpha was decreased 1 week post MI and the
      migration capacity to SDF-1alpha was negatively correlated with mncCD26
      expression. CD26 inhibition with sitagliptin - a drug currently used in diabetic
      patients - resulted in improved in vitro migration capacities of MNCs. In
      conclusion, our preliminary results suggest that high cellular CD26 expression
      decreases the migration of MNCs towards SDF-1alpha and high cellular CD26
      expression negatively influences cardiac function post MI. Treating patients
      shortly post MI with sitagliptin to inhibit CD26 may therefore increase MNC
      homing to the infarct area and could improve cardiac recovery and repair.

PMID- 22982115
TI  - Using metabolomics to assess myocardial metabolism and energetics in heart
      failure.
AB  - There is a long history of investigation into the metabolism of the failing
      heart. Congestive heart failure is marked both by severe disruptions in
      myocardial energy supply and an inability of the heart to efficiently uptake and
      oxidize fuels. Despite the many advancements in our understanding, there are
      still even more outstanding questions in the field. Metabolomics has the power to
      assist our understanding of the metabolic derangements which accompany myocardial
      dysfunction. Metabolomic investigations in animal models of heart failure have
      already highlighted several novel, potentially important pathways of substrate
      selection and toxicity. Metabolomic biomarker studies in humans, already
      successfully applied to other forms of cardiovascular disease, have the potential
      to improve diagnosis and patient care. This article is part of a Special Issue
      entitled "Focus on Cardiac Metabolism".

PMID- 22982116
TI  - Isolation of single chain variable fragment (scFv) specific for Cry1C toxin from
      human single fold scFv libraries.
AB  - As bioinsecticides Bacillus thuringiensis Cry1C delta-endotoxins also have been
      used in genetically modified crops worldwide since last century. In this study,
      single chain variable fragments (scFvs), which could specifically recognize and
      detect Cry1C in food samples, were isolated from naive phage displayed human
      antibody libraries (Tomlinson I + J) by iterative affinity selection procedure
      instead of immunization process. With increasing selection pressure, after four
      rounds of panning, three individual scFvs were obtained and sequenced. The
      antibodies were characterized by enzyme-linked immunosorbent assay (ELISA).
      Thereafter, a conformed novel anti-Cry1C scFv, namely scFv-H6, was expressed in
      Escherichia coli (E. coli) HB2151 and purified by Ni metal ion affinity
      chromatography. An indirect competitive ELISA assay (ic-ELISA) of scFv-H6 was
      developed for the determination of Cry1C toxin in the range from 0.023 MUg mL-1
      to 4.35 MUg mL-1, and 50% inhibition concentration (IC50) was 0.39 MUg mL-1. This
      approach showed ignorable cross-reactivity with toxin Cry1Ac and Cry1B (3.51% and
      7.28%, respectively). This ic-ELISA approach was exploited for the determination
      of Cry1C in spiked ground rice samples with a mean recovery rate of 92.5% and
      coefficient of variation (C.V.) less than 5.0%. This study proves that phage
      display libraries provide a valuable system for the low-cost, rapid and
      continuous generation of specific antibody fragments directed against toxin
      targets and develop a simple detection method. Our results show that anti-Cry1C
      scFv could be a valuable tool for detection of Cry1C in food and agricultural
      samples.

PMID- 22982117
TI  - Identification, cDNA cloning and heterologous expression of a hyaluronidase from
      the tarantula Brachypelma vagans venom.
AB  - Hyaluronidases (Hyal) present in the venom of poisonous animals have been
      considered as "spreading factors" that facilitate a fast penetration of the venom
      in the prey. We have found that hyaluronidase from the tarantula Brachypelma
      vagans venom (BvHyal) displays a substrate-specific Hyal activity against
      hyaluronan. By using a combined strategy based on peptide sequencing and RT-PCR,
      we have cloned a BvHyal cDNA. Active recombinant BvHyal was efficiently expressed
      in a baculovirus system in insect cell.

PMID- 22982118
TI  - Design and synthesis of pinanamine derivatives as anti-influenza A M2 ion channel
      inhibitors.
AB  - The adamantanes are a class of anti-influenza drugs that inhibit the M2 ion
      channel of the influenza A virus. However recently, the clinical effectiveness of
      these drugs has been called into question due to the emergence of adamantane
      insensitive A/M2 mutants. Although we previously reported (1R,2R,3R,5S)-3
      pinanamine 3 as a novel inhibitor of the wild type influenza A virus M2 protein
      (WT A/M2), limited inhibition was found for adamantane-resistant M2 mutants. In
      this study, we explored whether newly synthesized pinanamine derivatives were
      capable of inhibiting WT A/M2 and selected adamantane-resistant M2 mutants.
      Several imidazole and guanazole derivatives of pinanamine were found to inhibit
      WT A/M2 to a comparable degree as amantadine and one of these compounds 12
      exhibits weak inhibition of A/M2-S31N mutant and it is marginally more effective
      in inhibiting S31NM2 than amantadine. This study provides a new insight into the
      structural nature of drugs required to inhibit WT A/M2 and its mutants.

PMID- 22982119
TI  - Synthesis and biological activity of obatoclax derivatives as novel and potent
      SHP-1 agonists.
AB  - Obatoclax is a linear oligopyrrole compound which antagonizes the antiapoptotic
      effects of the Bcl-2 family. Herein we describe the synthesis of obatoclax
      derivatives by replacement of the pyrrole and indole ring of obatoclax with
      thiophene, furan and thiazolidinedione. The in vitro cytotoxicity of the newly
      synthesized compounds is evaluated against hepatocellular carcinoma cells.
      Pyrrole and indole substituents of obatoclax analogues exhibited potent
      inhibition of cell growth. Among the tested compounds, 5d and 5e were active at
      6.3 and 13.2 MUM against PLC5 cells. Further assays confirmed a correlation
      between cell death, and p-STAT3 inhibition and SHP-1 activation by these
      analogues.

PMID- 22982120
TI  - Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and
      eugenol.
AB  - The present works deals with simple and efficient method of improving therapeutic
      efficacy of racemic ibuprofen by retarding gastrointestinal side effects through
      masking of carboxylic group chemically. This is achieved by synthesis and
      evaluation of ester derivatives of ibuprofen as mutual prodrugs with naturally
      occurring phenolic and alcoholic compounds. Promoieties like menthol; thymol and
      eugenol were selected with the aim of getting synergistic effect as these are
      natural analgesic having traditional medicinal values. Prodrugs are found to be
      highly lipophilic as compared to parent drug. All the prodrugs are found to be
      highly stable at acidic pH while undergoes hydrolysis at neutral and alkaline pH
      as indicated by their t(1/2) values. Synthesized prodrugs derivatives show
      increased anti-inflammatory activity that might be attributed to synergistic
      effect as ibuprofen conjugates to natural analgesics. Ulcer index shows much
      reduction in gastric ulceration compared to ibuprofen concluding the successful
      masking of acidic group.

PMID- 22982121
TI  - Understanding the binding of daunorubicin and doxorubicin to NADPH-dependent
      cytosolic reductases by computational methods.
AB  - The anthracycline anticancer agents daunorubicin (DAUN) and doxorubicin (DOX) are
      reduced by different NADPH-dependent cytosolic reductases into their
      corresponding alcohol metabolites daunorubicinol (DAUNol) and doxorubicinol
      (DOXol), which have been implicated in the development of chronic cardiomyopathy.
      To better understand the individual importance of each enzyme in the reduction
      and to provide deeper insight into the binding at atomic level we performed
      molecular docking and dynamics simulations of DAUN and DOX into the active sites
      of human carbonyl reductase 1 (CBR1) and human aldehyde reductase (AKR1A1). Such
      simulations evidenced a different behavior between the reductases with respect to
      DAUN and DOX suggesting major contribution of CBR1 in the reduction. The results
      are in agreement with available experimental data and for each enzyme and
      anthracycline pair provided the identification of key residues involved in the
      interactions. The structural models that we have derived could serve as a useful
      tool for structure-guided drug design studies.

PMID- 22982122
TI  - Synthesis and biological evaluation of combretastatin-amidobenzothiazole
      conjugates as potential anticancer agents.
AB  - A series of combretastatin-amidobenzothiazole conjugates have been synthesized
      and evaluated for their anticancer activity. All these compounds exhibited
      significant anticancer activity and the most potent compound (11a) showed GI(50)
      values ranging 0.019-11 MUM. Biological studies such as cell cycle distribution,
      effect on tubulin polymerization and effect on ERK signalling pathway have been
      examined in MCF-7 cell line. FACS analysis revealed that these compounds induced
      cell cycle arrest at G2/M phase. Compound 11a showed significant effect on
      tubulin polymerization and affected the ERK signalling pathway that result in the
      decreased levels of ERK1/2, p-ERK and c-Jun proteins. Docking experiments have
      shown that the active molecules interact and bind well in the ATP binding pocket
      of ERK protein.

PMID- 22982123
TI  - Synthesis, antimicrobial and cytotoxicity study of 1,3-disubstituted-1H
      naphtho[1,2-e][1,3]oxazines.
AB  - A series of new 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines (3 and 7) was
      synthesized in good yields and the structure was determined with the help of NMR,
      2D-NMR, HRMS studies and X-ray crystallography. These compounds were tested in
      vitro for their antibacterial activity against Gram-positive and Gram-negative
      bacteria and as well as for antifungal activity. The compounds 3c, 3e, 7a, 7d and
      7k showed significant antibacterial activity and 7l showed moderate antifungal
      activity. The cytotoxicity of 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines
      showed that 3e and 7e are more effective against breast, lung and colon cell
      proliferation.

PMID- 22982124
TI  - Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted
      rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4
      thiazolidinone.
AB  - Four novel series of compounds, including the l-phenylalanine-derived C5
      substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing
      thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been
      designed, synthesized, characterized, and evaluated for their antibacterial
      activity. Some of these compounds showed significant antibacterial activity
      against Gram-positive bacterias, especially against the strains of multidrug
      resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q
      exhibiting high levels of antimicrobial activity against Staphylococcus aureus
      RN4220 with minimum inhibitory concentration (MIC) values of 2 MUg/mL. Compound
      6q showed the most potent activity of all of the compounds against all of the
      test multidrug-resistant clinical isolates tested. Unfortunately, however, none
      of the compounds were active against Gram-negative bacteria at 64 MUg/mL.

PMID- 22982125
TI  - A comparison of four sputum pre-extraction preparation methods for identifying
      and characterising Mycobacterium tuberculosis using GCxGC-TOFMS metabolomics.
AB  - In many pulmonary diseases, sputum is a valuable sample material for use in
      disease characterisation and diagnostics. However, due to its high viscosity and
      uneven consistency (lumpiness), it is difficult to obtain reproducible/repeatable
      results during compound extraction and analysis. We subsequently investigated and
      compared four sputum pre-extraction preparation methods using: 1) Sputolysin; 2)
      a combination of N-acetyl-l-cysteine and sodium hydroxide (NALC-NaOH); 3) NaOH
      alone, and 4) a simple ethanol homogenisation method, prior to sputum extraction
      and metabolomics analyses. The simple ethanol homogenisation approach proved to
      be the comparatively superior sputum pre-extraction preparation method,
      considering its repeatability, the number of characteristic compounds extracted,
      its ability to extract those compounds best differentiating the sample groups
      (Mycobacterium tuberculosis-spiked and clinically confirmed TB-positive patient
      samples from each of the controls respectively), and its detection limit. This
      developed methodology subsequently allows for accurate GC based analyses of
      sputum, and hence, could contribute significantly to the better characterisation
      or diagnostics of not only tuberculosis, but also potentially other pulmonary
      diseases, including, interstitial lung disease, cystic fibrosis, lung cancer,
      pneumonia and any other bacterial induced pulmonary diseases producing sputum.

PMID- 22982126
TI  - [Screening practices for hepatitis B virus prior to viral reactivation risk
      therapies among different medical specialties. HEBRA Project].

PMID- 22982127
TI  - [Transparency in clinical research: registration of clinical trials and
      publication of results].

PMID- 22982128
TI  - [Prioritization of health interventions according to their effectiveness: an
      intermediate step in the road towards a more efficient medicine].

PMID- 22982129
TI  - [Stroke in the very old: myths and realities].

PMID- 22982130
TI  - [Trends in the prevalence of extended-spectrum beta-lactamase-producing gram
      negative bacilli in a teaching hospital in Madrid, Spain].
AB  - BACKGROUND AND OBJECTIVE: The pprevalence of extended-spectrum beta-lactamase
      (ESBL) producing gram-negative bacilli has increased in recent years. The aim of
      this study is to estimate the prevalence of infection/colonization due to theses
      microorganisms per 100 admissions and its trend during the period 2007-2010.
      PATIENTS AND METHODS: Prospective observational study of all patients admitted
      from January 2007 to December 2010 infected or colonized with ESBL-producing gram
      negative bacilli at Hospital Universitario Ramon y Cajal. The prevalence of
      infection/colonization of ESBL-producing gram-negative rods was calculated
      according to the recommendations for metrics for multidrug-resistant organisms in
      healthcare settings of The Society for Healthcare Epidemiology of America and the
      Healthcare Infection Control Practices Advisory Committee. To analyse trends,
      Poisson regression was used (Joinpoint Regression Program Version 3.4.3, U.S.
      National Institutes of Health). RESULTS: Through the study period there was an
      upward trend of prevalence of all the ESBL-producing gram-negative bacilli. The
      Poisson trend analysis indentified a significant inflection point in August 2009
      (p=0.014). CONCLUSION: The inflection point in the prevalence of the ESBL
      producing gram-negative bacilli trend can be explained by a slowdown in the
      prevalence of some microorganisms such as ESBL-producing Klebsiella pneumoniae.

PMID- 22982131
TI  - [Update of the usefulness of alpha-blockers in the treatment of different
      urologic pathologies].
AB  - OBJECTIVE: To review the role of alpha-blockers in various urological conditions
      such as benign prostatic hyperplasia, overactive bladder, chronic prostatitis,
      and erectile dysfunction and as expulsive treatment of distal ureteral stones.
      MATERIAL AND METHODS: We reviewed the latest scientific evidence in all the
      fields mentioned above, performing a critical analysis. CONCLUSION: alpha
      blockers are now considered first-line treatment in lower urinary tract symptoms
      secondary to benign prostatic hyperplasia, but the indications go beyond, and are
      able to improve, alone or in combination with other drugs, the previously
      mentioned pathologies. The uroselective properties of some alpha-blockers make
      them a highly safe medication.

PMID- 22982132
TI  - [Predictors of reversion to sinus rhythm previous to electrical cardioversion in
      patients with persistent atrial fibrillation treated with anti-arrhythmic drugs].
AB  - BACKGROUND: Some patients with persistent atrial fibrillation treated
      pharmacologically revert to sinus rhythm prior to electrical cardioversion.
      Knowledge of factors predicting this effect may be clinically useful.
      METHODOLOGY: Data were obtained from patients enrolled in the study REgistro
      sobre la cardioVERSion en Espana (REVERSE) and treated with antiarrhythmic drugs
      that potentially may cause pharmacological reversal. We analized by means of
      logistic regression predictive factors related to reversion to sinus rhythm
      precardioversion. RESULTS: Of the 752 patients treated with antiarrhythmic drugs,
      160 (21%) reverted to sinus rhythm without electrical cardioversion. Amiodarone
      was the most widely used active compound (82%) and apparently the most effective.
      However, differences with other antiarrhythmic drugs were not significant
      (amiodarone 22% versus other antiarrhythmic drugs 17%, P = .22). Lack of obesity
      (body mass index < 30 kg/m(2)) (odds ratio [OR] = 1.9; P = .006), duration of
      atrial fibrillation < 1 year (OR 3.4; P=.02) and the absence of structural heart
      disease (OR 1,59; P = .01) were identified as independent variables with
      predictive value of pharmacological reversal to sinus rhythm. Among patients
      treated with amiodarone who met these criteria, the frequency of successful
      treatment increased up to 31%. CONCLUSION: In patients with persistent atrial
      fibrillation treated with anti-arrhythmic drugs, lack of obesity, duration of
      atrial fibrillation < 1 year and the absence of structural heart disease are
      predictors of reversion to sinus rhythm before electrical cardioversion.

PMID- 22982135
TI  - Updating JPROT's publication standards for large-scale proteomic studies: towards
      hypothesis-driven interpretation of predictive biological models.

PMID- 22982136
TI  - Systems biology of stored blood cells: can it help to extend the expiration date?
AB  - With increasingly stringent regulations regarding deferral and elimination of
      blood donors it will become increasingly important to extend the expiration date
      of blood components beyond the current allowed storage periods. One reason for
      the storage time limit for blood components is that platelets and red blood cells
      develop a condition called storage lesions during their storage in plastic blood
      containers. Systems biology provides comprehensive bio-chemical descriptions of
      organisms through quantitative measurements and data integration in mathematical
      models. The biological knowledge for a target organism can be translated in a
      mathematical format and used to compute physiological properties. The use of
      systems biology represents a concrete solution in the study of blood cell storage
      lesions, and it may open up new avenues towards developing better storage methods
      and better storage media, thereby extending the storage period of blood
      components. This article is part of a Special Issue entitled: Integrated omics.

PMID- 22982137
TI  - Modelling the spread of diseases in clustered networks.
AB  - It is now well appreciated that population structure can have a major impact on
      disease dynamics, outbreak sizes and epidemic thresholds. Indeed, on some
      networks, epidemics occur only for sufficiently high transmissibility, whereas in
      others (e.g. scale-free networks), no such threshold effect exists. While the
      effects of variability in connectivity are relatively well known, the effects of
      clustering in the population on disease dynamics are still debated. We develop a
      simple and intuitive model for calculating the reproductive number R(0) on
      clustered networks with arbitrary degree distribution. The model clearly shows
      that in general, clustering impedes epidemic spread; however, its effects are
      usually small and/or coupled with other topological properties of the network.
      The model is generalized to take into account degree-dependent transmissibility
      (e.g., relevant for disease vectors). The model is also used to easily rederive a
      known result concerning the formation of the giant component.

PMID- 22982138
TI  - Bayesian statistical analysis of circadian oscillations in fibroblasts.
AB  - Precise determination of a noisy biological oscillator's period from limited
      experimental data can be challenging. The common practice is to calculate a
      single number (a point estimate) for the period of a particular time course.
      Uncertainty is inherent in any statistical estimator applied to noisy data, so
      our confidence in such point estimates depends on the quality and quantity of the
      data. Ideally, a period estimation method should both produce an accurate point
      estimate of the period and measure the uncertainty in that point estimate. A
      variety of period estimation methods are known, but few assess the uncertainty of
      the estimates, and a measure of uncertainty is rarely reported in the
      experimental literature. We compare the accuracy of point estimates using six
      common methods, only one of which can also produce uncertainty measures. We then
      illustrate the advantages of a new Bayesian method for estimating period, which
      outperforms the other six methods in accuracy of point estimates for simulated
      data and also provides a measure of uncertainty. We apply this method to analyze
      circadian oscillations of gene expression in individual mouse fibroblast cells
      and compute the number of cells and sampling duration required to reduce the
      uncertainty in period estimates to a desired level. This analysis indicates that,
      due to the stochastic variability of noisy intracellular oscillators, achieving a
      narrow margin of error can require an impractically large number of cells. In
      addition, we use a hierarchical model to determine the distribution of intrinsic
      cell periods, thereby separating the variability due to stochastic gene
      expression within each cell from the variability in period across the population
      of cells.

PMID- 22982139
TI  - The molecular basis for the distinct host and tissue tropisms of coccidian
      parasites.
AB  - The phylum Apicomplexa is home to a variety of parasites of significant medical
      and economic relevance, including the coccidian species Toxoplasma gondii,
      Neospora caninum and Eimeria tenella. In spite of their shared ancestry, the
      aforementioned coccidian species exhibit highly variable host and tissue
      tropisms; whilst T. gondii invades a broad spectrum of cell types and host
      organisms, E. tenella infection is restricted to the caecum in chicken.
      apicomplexans are obligatory intracellular parasites, and are uniquely adapted
      for host cell invasion via several conserved features. The process of initial
      host cell recognition and attachment is governed by the regulated deployment of
      surface microneme proteins (MICs), which therefore are likely to be major
      determinants of the host and tissue tropism of each parasite. Structural and
      functional data are now available for several coccidian MICs, providing insights
      into their receptor specificities and modes of recognition in atomic detail.
      Here, detailed analysis of these data has been performed, encouraging
      rationalization of the marked differences in the host and tissue tropism. We have
      observed that T. gondii expresses a wide repertoire of MICs, binding a broad
      range of oligosaccharide epitopes, including a unique preference for a alpha2,9
      disialyl terminated receptor. By contrast, the MIC repertoire of Neospora caninum
      appears to be more restrictive, and even further so in E. tenella, correlating
      with the reduced tropisms of these parasites.

PMID- 22982140
TI  - Essential role of toll-like receptor 4 in Acinetobacter baumannii-induced immune
      responses in immune cells.
AB  - TLR4 is a membrane sensor for lipopolysaccharide (LPS), a major cell wall
      component of gram-negative bacteria. In this study, we investigated the role of
      TLR4 on innate immune responses in immune cells against Acinetobacter baumannii.
      Bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) were isolated
      from WT and TLR4-deficient mice and infected with A. baumannii ATCC 15150. ELISA
      assay revealed that the production of IL-6 and TNF-alpha by A. baumannii was
      impaired in TLR4-deficient macrophages. However, absence of TLR2 did not affect
      A. baumannii-induced cytokines production in BMDMs. In addition, TLR4 was
      required for the optimal production of IL-6, TNF-alpha, and IL-12 in BMDCs in
      response to A. baumannii. Western blot analysis showed that A. baumannii leads to
      the activation of NF-kappaB and MAPKs (p38, ERK, and JNK) in macrophages via TLR4
      dependent pathway. mRNA expression of iNOS and NO production was elicited in WT
      BMDMs in response to A. baumannii, which was abolished in TLR4-deficienct cells.
      Bacterial killing ability against A. baumannii was impaired in TLR4-deficient
      BMDMs. In addition, A. baumannii induced apoptosis in BMDMs via TLR4-independent
      pathway. Our results demonstrate that TLR4 is essential for initiating innate
      immune response of macrophages against A. baumannii infection.

PMID- 22982141
TI  - Arterial stiffness and novel biomarkers in patients with abdominal aortic
      aneurysms.
AB  - OBJECTIVES: Pulse wave velocity (PWV) constitutes a valid index of arterial
      stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established
      vascular calcification inhibitors, highly correlated with inflammation, and
      cardiovascular events incidence. We investigated the association of PWV with the
      aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA).
      METHODS: We enrolled 108 men with AAA (AAA group) candidates for endovascular
      repair. We excluded patients with Marfan syndrome or other collagen-related
      disorders. Forty-one age-matched men, with stable coronary artery disease (CAD),
      but without AAA, served as controls (CO group). PWV, clinical parameters and
      serum levels of osteoprotegerin (OPG), osteopontin (OPN), interleukin-6 (IL-6)
      and IL-10 were determined. RESULTS: With the exception of higher smoking rate and
      the lower statin's usage in the AAA group, there were non-significant differences
      in the rest of demographic and clinical parameters (p>0.05). We found
      significantly higher levels of PWV in AAA than CO group (12.99+/-3.75 m/s vs
      10.03+/-1.57 m/s, p<0.001). In parallel, serum OPG, OPN, IL-6 levels were
      considerably increased, while IL-10 levels were downregulated (p<0.001) in AAA
      group. PWV positively correlated with mean blood pressure, OPG concentrations and
      AAA diameter in univariate and multivariate analysis (R(2)=0.498, p=0.008).
      Finally, age and OPG remained independent determinants of AAA presence in the
      whole study cohort. CONCLUSIONS: Arterial stiffness, circulating vascular
      calcification inhibitors and inflammatory mediators seem to be significantly
      upregulated in patients with AAA. An independent association of PWV with mean
      blood pressure, OPG and AAA diameter is of clinical importance which requires
      further investigation.

PMID- 22982142
TI  - Activation of vagus nerve by semapimod alters substance P levels and decreases
      breast cancer metastasis.
AB  - Chronic inflammation is involved in initiation as well as in progression of
      cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493,
      inhibits the release of inflammatory cytokines from activated macrophages and
      this effect is partly mediated by the vagus nerve. Our previous findings
      demonstrated that inactivation of vagus nerve activity as well sensory neurons
      enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by
      activating vagus nerve may inhibit breast cancer metastasis. Here, effects of
      semapimod on breast cancer metastasis, the role of vagal sensory neurons on this
      effect and changes in mediators of the neuroimmune connection, such as substance
      P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed
      on half of the control animals that were treated with semapimod following
      orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and
      liver metastases in control but not in vagotomized animals with an associated
      increased SP levels in sensory nerve endings. Semapimod also increased neprilysin
      like activity in lung tissue of control animals but not in tumor-bearing animals.
      This is the first report demonstrating that semapimod enhances vagal sensory
      nerve activity and may have anti-tumoral effects under in-vivo conditions.
      Further studies, however, are required to elucidate the conditions and the
      mechanisms involved in anti-tumoral effects of semapimod.

PMID- 22982143
TI  - Neural tracts injuries in patients with hypoxic ischemic brain injury: diffusion
      tensor imaging study.
AB  - Many studies have reported on vulnerable areas of the brain in hypoxic ischemic
      brain injury (HI-BI). However, little is known about the involvement of neural
      tracts following HI-BI. We investigated neural tract injuries in adult patients
      with HI-BI, using diffusion tensor tractography (DTT). Twelve consecutive
      patients with HI-BI and 12 control subjects were recruited for this study. We
      classified the patients into two subgroups according to the preservation of
      alertness: subgroup A-5 patients who had intact alertness and subgroup B-7
      patients who had impaired alertness. DTI-Studio software was used for evaluation
      of seven neural tracts: corticospinal, cingulum, fornix, superior longitudinal
      fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital
      fasciculus, and optic radiation. We measured the DTT parameters (fractional
      anisotropy, apparent diffusion coefficient and voxel number) of each neural
      tract. In the individual analysis, all 12 patients showed injuries in all 24
      neural tracts in terms of both DTT parameters and integrity, except for the
      corticospinal tract (75.0% injury). In the group analysis, the patient group
      showed neural injuries in all 24 neural tracts. In comparison of subgroups A and
      B, subgroup B showed more severe injuries: subgroup B showed a higher rate of
      disruption (39.8%) than subgroup A (12.9%) on individual DTTs and subgroup B had
      more severe injuries in both the cingulum and superior longitudinal fasciculus.
      In conclusion, we found that extensive injuries in the neural tracts were
      accompanied by HI-BI. Patients with impaired alertness appeared to show more
      severe injuries of neural tracts.

PMID- 22982144
TI  - Methylation mediated silencing of miR-23b expression and its role in glioma stem
      cells.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate
      gene expression at a post-transcriptional level. Some miRNAs harboring CGIs
      undergo methylation mediated silencing, a characteristic of many tumor suppressor
      genes. To identify such miRNAs in glioma stem cells (GSCs), we first showed that
      miR-23b is frequently methylated in GSCs but not in parallel U87 cells.
      Meanwhile, miR-23b expression was also markedly reduced in GSCs compared with
      matching U87 cells. Furthermore, treatment with 5-aza can increase miR-23b
      expression in GSCs. In addition, ectopic expression of miR-23b in GSCs induces
      cell cycle arrest and proliferation inhibition. Further analysis showed that miR
      23b could enhance the sensitivity of U87 GSCs to TMZ. Our results suggest that
      miR-23b is epigenetically down-regulated and restoration of miR-23b can
      effectively suppress cell growth in GSCs.

PMID- 22982145
TI  - Protective effect of N,N'-dialkylated analogs of 4,4'-diaminodiphenylsulfone in a
      model of intrastriatal quinolinic acid induced-excitotoxicity.
AB  - The bacteriostatic agent 4,4'-diaminodiphenylsulfone or dapsone (DDS) and some of
      its N,N'-dialkylated analogs have shown anticonvulsant and neuroprotective
      properties in different experimental models. In this study, we tested the ability
      of five DDS analogs (N,N'-dimethyldapsone, N,N'-diethyldapsone, N,N'
      dipropyldapsone, N,N'-dibutyldapsone and N,N'-ditosyldapsone) to attenuate
      quinolinic acid-induced toxicity in vivo. Male Wistar rats were treated with
      either DDS or analogs (12.5mg/kg and equimolar doses respectively) 30 min before
      quinolinic acid intrastriatal stereotaxic injection (240 nmol/MUl). Six days
      after injury, circling behavior was evaluated by counting ipsilateral turns for
      1h after apomorphine challenge (1mg/kg, sc). Twenty-four hours later, rats were
      sacrificed and their corpora striata were dissected out to determine GABA
      content. Hemotoxicity of the analogs was assessed as the ability to produce
      methemoglobin (MHb) in vivo. Blood was sampled from tail vein within 18 h after
      drugs administration. Methemoglobin levels were determined by visible
      spectrophotometry and mean profiles of MHb-percentage versus time were obtained.
      All of the analogs tested decreased the number of ipsilateral turns/hour,
      reducing up to 67% the turns counting (p<0.05) when compared to those induced in
      animals receiving quinolinic acid with no treatment. N,N'-dimethylated, N,N'
      diethylated and N,N'-dibutylated analogs significantly prevented the decrease of
      intrastriatal GABA content (p<0.05). Methemoglobin produced by the administration
      of analogs was significantly lower than the levels of the group receiving dapsone
      (p<0.05). The neuroprotective effect of analogs and their diminished hemotoxicity
      make them potential candidates for therapeutic applications.

PMID- 22982146
TI  - Local administration of L-DOPA in the chicken ventromedial hypothalamus increases
      dopamine release in a dose-dependent manner.
AB  - L-DOPA induced extracellular dopamine (DA), norepinephrine (NE) and serotonin (5
      HT) in the ventromedial hypothalamus (VMH) of chickens were measured by in vivo
      microdialysis. Several doses of 3,4-dihydroxy-l-phenylalanine (l-DOPA) were
      administered locally through the microdialysis probe into the VMH of chickens for
      10 min. Local perfusion of l-DOPA increased the extracellular levels of DA. The
      increased DA was dose-related and was significantly higher compared to the
      baseline and control group. The maximal level of DA was 212% and 254%,
      respectively, of the baseline following administration of 1 and 2 MUg/ml l-DOPA.
      There were no changes in NE and 5-HT levels from baseline after l-DOPA perfusion.
      l-DOPA (1 MUg/ml) was mixed with Ca(2+)-free Ringer, tetrodotoxin (TTX) (2 MUM)
      and high K(+) and was perfused for 30 min into the chicken VMH. TTX and Ca(2+)
      free Ringer's solution inhibited the effectiveness of l-DOPA in increasing DA
      release. The NE and 5-HT levels were significantly lower than the baseline. After
      administration of K(+) a significant increase of DA, NE and 5-HT was observed.
      The microdialysis results are consistent with our objective that l-DOPA induced
      extracellular DA increases in the VMH in a dose-dependent manner and the released
      DA, NE and 5-HT within the dialysate were related to neuronal activity.

PMID- 22982147
TI  - Effects of intrahippocampal L-NAME treatment on the behavioral long-term
      potentiation in dentate gyrus.
AB  - Using a combination of electrophysiological recordings, behavioral tests and
      local pharmacological administration in hippocampus, we investigated in the
      present study the effects of nitric oxide (NO) synthase inhibitor N-nitro-l
      arginine methyl ester (l-NAME) on the behavioral long-term potentiation (LTP) and
      maze learning performance in freely moving rats. The results showed as follows:
      (1) intrahippocampal l-NAME administration led to a defect in maze learning
      performance of the animals; (2) l-NAME treatment also substantially impaired the
      induction of the behavioral LTP in perforant pathway to dentate gyrus (PP-DG)
      pathway induced by maze learning task, while it had no significant effects on
      basic synaptic transmission in PP-DG pathway; Collectively, these results
      indicate that NO synthesis may be critical for the behavioral LTP in PP-DG
      pathway and maze learning performance.

PMID- 22982148
TI  - Cushing's mechanism maintains cerebral perfusion pressure in experimental
      subarachnoid haemorrhage.
AB  - Mortality following subarachnoid haemorrhage (SAH) is high, especially within the
      first 48 h. Poor outcome is predicted by high intracranial pressure which causes
      diminished cerebral perfusion pressure unless a compensatory increase in mean
      arterial blood pressure occurs. Therefore blood pressure elevation can be
      protective following subarachnoid haemorrhage despite the potential for
      rebleeding. This study investigated blood pressure responses to SAH and the
      impact on cerebral perfusion pressure and outcome, as demonstrated by two
      experimental models. Various blood pressure responses were demonstrated, both at
      the ictus and within the following 5h. Elevated MABP at the ictus and at 2h
      following experimental SAH was associated with maintenance of CPP in the presence
      of raised ICP. Poor outcome (arrest of the cerebral circulation) was predicted by
      failure of MABP to increase significantly above sham levels within 2h of SAH. Rat
      SAH provides relatively inexpensive models to investigate physiological
      mechanisms that maintain cerebral perfusion in the presence of intracranial
      hypertension.

PMID- 22982150
TI  - Virulence factors of schistosomes.
AB  - This review considers whether the products of schistosomes in the mammalian host
      can be considered as virulence factors. These include: the cercarial secretions
      used in infection, those of the migrating schistosomulum, surface-exposed
      proteins of adult worms in the portal system and their gut vomitus in the context
      of immune evasion, secretions of the egg facilitating its escape from gut tissues
      and micro-exon gene products.

PMID- 22982149
TI  - cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons.
AB  - Proteasome impairment and accumulation of ubiquitinated proteins are implicated
      in neurodegeneration associated with different forms of spinal cord injury. We
      show herein that elevating cAMP in rat spinal cord neurons increases 26S
      proteasome activity in a protein kinase A-dependent manner. Treating spinal cord
      neurons with dibutyryl-cAMP (db-cAMP) also raised the levels of various
      components of the UPP including proteasome subunits Rpt6 and beta5, polyubiquitin
      shuttling factor p62/sequestosome1, E3 ligase CHIP, AAA-ATPase p97 and the
      ubiquitin gene ubB. Finally, db-cAMP reduced the accumulation of ubiquitinated
      proteins, proteasome inhibition, and neurotoxicity triggered by the endogenous
      product of inflammation prostaglandin J2. We propose that optimizing the effects
      of cAMP/PKA-signaling on the UPP could offer an effective therapeutic approach to
      prevent UPP-related proteotoxicity in spinal cord neurons.

PMID- 22982151
TI  - Molecular phylogenetics, species diversity, and biogeography of the Andean
      lizards of the genus Proctoporus (Squamata: Gymnophthalmidae).
AB  - The family Gymnophthalmidae comprises ca. 220 described species of Neotropical
      lizards distributed from southern Mexico to Argentina. It includes 36 genera,
      among them Proctoporus, which contains six currently recognized species occurring
      across the yungas forests and wet montane grasslands of the Amazonian versant of
      the Andes from central Peru to central Bolivia. Here, we investigate the
      phylogenetic relationships and species limits of Proctoporus and closely related
      taxa by analyzing 2121 base pairs of mitochondrial (12S, 16S, and ND4) and
      nuclear (c-mos) genes. Our taxon sampling of 92 terminals includes all currently
      recognized species of Proctoporus and 15 additional species representing the most
      closely related groups to the genus. Maximum parsimony, maximum likelihood and
      Bayesian phylogenetic analyses recovered a congruent, fully resolved, and
      strongly supported hypothesis of relationships that challenges previous
      phylogenetic hypotheses and classifications, and biogeographic scenarios. Our
      main results are: (i) discovery of a strongly supported clade that includes all
      species of Proctoporus and within which are nested the monotypic Opipeuter xestus
      (a genus that we consider a junior synonym of Proctoporus), and two species of
      Euspondylus, that are therefore transferred to Proctoporus; (ii) the paraphyly of
      Proctoporus bolivianus with respect to P. subsolanus, which is proposed as a
      junior synonym of P. bolivianus; (iii) the detection of seven divergent and
      reciprocally monophyletic lineages (five of them previously assigned to P.
      bolivianus) that are considered confirmed candidate species, which implies that
      more candidate species are awaiting formal description and naming than currently
      recognized species in the genus; (iv) rejection of the hypothesis that
      Proctoporus diversified following a south to north pattern parallel to the
      elevation of the Andes; (v) species diversity in Proctoporus is the result of in
      situ diversification through vicariance in the grasslands of the high Andes, with
      at least five dispersals contributing to montane forest species.

PMID- 22982152
TI  - BDNF: the career of a multifaceted neurotrophin in spinal cord injury.
AB  - Brain-derived neurotrophic factor (BDNF) has been identified as a potent promoter
      of neurite growth, a finding that has led to an ongoing exploration of this
      neurotrophin as a potential treatment for spinal cord injury. BDNF's many effects
      in the nervous system make it an excellent candidate for neuroprotective
      strategies as well as for promoting axonal regeneration, plasticity and re
      myelination. In addition, neuronal activity and physical exercise can modulate
      the expression of BDNF, suggesting that non-invasive means to increase BDNF
      levels might exist. Nonetheless, depending on the location, amount and duration
      of BDNF delivery, this potent neurotrophin can also have adverse effects, such as
      modulation of nociceptive pathways or contribution to spasticity. Taken together,
      the benefits and possible risks require careful assessment when considering this
      multifaceted neurotrophin as a treatment option for spinal cord injury.

PMID- 22982153
TI  - Androgen receptor in triple negative breast cancer.
AB  - The clinical management of triple negative breast cancer (TNBC) is challenging
      due to the relatively aggressive biological behaviour and paucity of specific
      targeted therapy. A subset of TNBC patients has been reported to express androgen
      receptor (AR) in carcinoma cells and the manipulation of androgen signalling or
      AR targeted therapies have been proposed. However, the biological significance of
      AR in TNBC has remained relatively unknown. Therefore, this review aims to
      summarise the reported studies assessing the rates of AR positivity in TNBC
      patients and androgenic effects in TNBC cell lines. The rates of AR positivity
      among TNBC cases varied depending on the study population (0-53% of all TNBC
      patients). This difference among the reported studies may be largely due to the
      methodological differences of analysing AR. While the majority of cell line
      studies suggest that androgen increase proliferation and preliminary clinical
      studies suggest that AR antagonists improve the prognosis of AR positive TNBC
      patients, cell line transfection experiments and survival analyses of
      histological samples suggest that the presence of AR in tumour is either benign
      or predicts better survival. Therefore further translational investigations
      regarding the mechanisms of androgen action in TNBC are required to explain this
      discrepancy between clinical and basic studies.

PMID- 22982154
TI  - Electrical and mechanical recovery of cardiac function following out-of-hospital
      cardiac arrest.
AB  - BACKGROUND: Compression pauses may be particularly harmful following the
      electrical recovery but prior to the mechanical recovery from cardiopulmonary
      arrest. METHODS AND RESULTS: A convenience sample of patients with out-of
      hospital cardiac arrest (OOHCA) were identified. Data were exported from
      defibrillators to define compression pauses, electrocardiogram rhythm, PetCO2,
      and the presence of palpable pulses. Pulse-check episodes were randomly assigned
      to a derivation set (one-third) and a validation set (two-thirds). Both an
      unweighted and a weighted receiver-operator curve (ROC) analysis were performed
      on the derivation set to identify optimal thresholds to predict ROSC using heart
      rate and PetCO2. A sequential decision guideline was generated to predict the
      presence of ROSC during compressions and confirm perfusion once compressions were
      stopped. The ability of this decision guideline to correctly identify pauses in
      which pulses were and were not palpated was then evaluated. A total of 145
      patients with 349 compression pauses were included. The ROC analyses on the
      derivation set identified an optimal pre-pause heart rate threshold of >40 beats
      min(-1) and an optimal PetCO2 threshold of >20 mmHg to predict ROSC. A sequential
      decision guideline was developed using pre-pause heart rate and PetCO2 as well as
      the PetCO2 pattern during compression pauses to predict and rapidly confirm ROSC.
      This decision guideline demonstrated excellent predictive ability to identifying
      compression pauses with and without palpable pulses (positive predictive value
      95%, negative predictive value 99%). The mean latency period between recovery of
      electrical and mechanical cardiac function was 78 s (95% CI 36-120 s).
      CONCLUSIONS: Heart rate and PetCO2 can predict ROSC without stopping
      compressions, and the PetCO2 pattern during compression pauses can rapidly
      confirm ROSC. Use of a sequential decision guideline using heart rate and PetCO2
      may reduce unnecessary compression pauses during critical moments during recovery
      from cardiopulmonary arrest.

PMID- 22982155
TI  - Hyperoxemic reperfusion after prolonged cardiac arrest in a rat cardiopulmonary
      bypass resuscitation model.
AB  - BACKGROUND: The effect of hyperoxygenation at reperfusion, particularly in the
      setting of cardiac arrest, remains unclear. This issue was studied in a prolonged
      cardiac arrest model consisting of 25 min cardiac arrest in a rat resuscitated
      with cardiopulmonary bypass (CPB). The objective of this study was to determine
      the effect of hyperoxygenation following prolonged cardiac arrest resuscitation
      on mitochondrial and cardiac function. METHODS: Male Sprague-Dawley rats (400-450
      g) were anesthetized with ketamine and xylazine and instrumented for closed chest
      cardiopulmonary bypass (CPB). Following a 25-min KCl-induced cardiac arrest, the
      animals were resuscitated by CPB with 100% oxygen. Three minutes after successful
      return of spontaneous circulation (ROSC), the animals received either normoxemic
      reperfusion (CPB with 40-50% oxygen) or hyperoxemic reperfusion (CPB with 100%
      oxygen) for 1 h. Post-resuscitation hemodynamics, cardiac function, mitochondrial
      function and immunostaining of 3-nitrotyrosine were compared between the two
      different treatment groups. RESULTS: At 1 h after ROSC, the hyperoxemic
      reperfusion group had a significant higher mean arterial pressure, less metabolic
      acidosis and better diastolic function than the normoxemic reperfusion group.
      Cardiac mitochondria from the hyperoxemic reperfusion group had a higher
      respiratory control ratio (RCR) and cardiac tissue showed less nitroxidative
      stress compared to the normoxemic reperfusion group. CONCLUSIONS: One hour of
      hyperoxemic reperfusion after 25 min of cardiac arrest in an in vivo CPB model
      resulted in significant short-term improvement in myocardial and mitochondrial
      function compared with 1h of normoxemic reperfusion. This myocardial response may
      differ from previously reported post-arrest hyperoxia mediated effects following
      shorter arrest times.

PMID- 22982156
TI  - Factors associated with genotype clustering of Mycobacterium tuberculosis
      isolates in an ethnically diverse region of southern California, United States.
AB  - Mycobacterium tuberculosis (Mtb) isolates with identical genotypes, found in
      different patients, are most likely the result of recent transmission. Mtb
      strains with closely related genotypes, called clonal complexes, are most likely
      derived from one another. We examined Mtb genotypes from southern California TB
      patients from 2005 through 2008 to complete the first comprehensive molecular
      epidemiology analysis of this complicated and ethnically diverse region. Mtb
      genotypes were characterized with spoligotype and MIRU-12 typing. MIRU-VNTRplus
      was utilized to assign genotypes to global lineages and complete cluster
      analyses. Associations between patient characteristics and genotype clustering
      and clonal complexes were evaluated using logistic regression and frequency
      analysis. Of 832 Mtb isolates analyzed, 480 (58%) fell into 94 strain clusters.
      The majority of isolates were identified as being in the EA1 (31%), LAM (17%) and
      Haarlem (15%) lineages, but 13 different lineages were found in this region. TB
      patients with clustered isolates were more likely to be homeless (AOR 3.44, 95%
      CI 1.65, 7.18) and male (AOR 1.57, 95% CI 1.17, 2.10). Of the 480 clustered
      strains, 388 aggregated into six clonal complexes. Over 45% of reported TB cases
      were clustered and likely resulted from recent transmission events. Patients with
      clustered Mtb isolates that were grouped into clonal complexes had unique socio
      demographic characteristics. These data suggest that TB is being transmitted in
      relatively insular community networks defined by race/ethnicity and country of
      origin. The addition of clonal complex analysis to simple cluster analysis
      provides important public health insights into the local transmission of TB in
      ethnically diverse regions with diverse Mtb genotypes.

PMID- 22982157
TI  - Scarce events of mitochondrial introgression in Trypanosoma cruzi: new case with
      a Bolivian strain.
AB  - Trypanosoma cruzi, the agent of Chagas disease, presents a predominantly clonal
      structure that has been shaped by recombination events leading to six genetic
      groups (DTUs, discrete typing units, TcI-TcVI). Several conventional and
      unconventional genetic exchange events have been described, including
      hybridization and mitochondrial introgression, which is explored here among
      Bolivian and Peruvian strains belonging to TcI because recombination events have
      been previously suspected by means of the MLMT method (multilocus microsatellite
      typing). We analyzed the variation of one nuclear (Gpi) and one mitochondrial
      (Nd1) gene among 60 TcI strains and 15 reference strains belonging to the six
      DTUs. The results clearly showed that one strain isolated from Triatoma infestans
      in the Cochabamba department (Bolivia) presented a genotype TcI for Gpi and a
      mitochondrial Nd1 genotype common to the DTUs TcIII, IV, V, and VI; this can be
      interpreted as a mitochondrial introgression event between distant DTUs. These
      kinds of events, although probably scarce, may have played an important role in
      the adaptive evolution of the species.

PMID- 22982158
TI  - Highlights on molecular identification of closely related species.
AB  - The term "complex" emerged in the literature at the beginning of the genomic era
      associated to taxonomy and grouping organisms that belong to different species
      but exhibited similar patterns according to their morphological, physiological
      and/or other phenotypic features. DNA-DNA hybridization values ~70% and high
      identity on 16S rRNA gene sequences were recommended for species delineation.
      Electrophoretic methods showed in some cases to be useful for species
      identification and population structure but the reproducibility was questionable.
      Later, the implementation of polyphasic approaches involving phenotypic and
      molecular methods brought new insights into the analysis of population structure
      and phylogeny of several "species complexes", allowing the identification of new
      closely related species. Likewise, the introduction of multilocus sequence typing
      and sequencing analysis of several genes offered an evolutionary perspective to
      the term "species complex". Several centres worldwide have recently released
      increasing genetic information on distinct microbial species. A brief review will
      be presented to highlight the definition of "species complex" for selected
      microorganisms, mainly the prokaryotic Acinetobacter calcoaceticus -Acinetobacter
      baumannii, Borrelia burgdorferi sensu lato, Burkholderia cepacia, Mycobacterium
      tuberculosis and Nocardia asteroides complexes, and the eukaryotic Aspergillus
      fumigatus, Leishmania donovani and Saccharomyces sensu stricto complexes. The
      members of these complexes may show distinct epidemiology, pathogenicity and
      susceptibility, turning critical their correct identification. Dynamics of
      prokaryotic and eukaryotic genomes can be very distinct and the term "species
      complex" should be carefully extended.

PMID- 22982159
TI  - Multiplexed microsatellite loci in American crow (Corvus brachyrhynchos): a
      severely affected natural host of West Nile virus.
AB  - Recent advances in high throughput molecular techniques have allowed the
      development of cost- and time-effective libraries of molecular markers, such as
      microsatellites, for population genetic studies in non-model species. The
      American crow, Corvus brachyrhynchos, is recognized to be one of the species that
      has been most negatively affected by the emergence of West Nile virus (WNV) in
      North America in 1999. Genetic monitoring of the process of a declining
      population after the introduction of an infectious disease can provide insights
      into the demographic and evolutionary impact of a pathogen in a natural host
      population over time. In this study, shotgun pyrosequencing and validation of
      previously published cross-species markers were the approaches used to identify
      and develop a set of 32 polymorphic loci for the C. brachyrhynchos. Since the
      American crow is morphologically similar to the sympatric species Fish crow
      (Corvus ossifragus), we also designed a real-time PCR protocol to rapidly
      differentiate these two species using a set of primers and probes that can
      discriminate a section of the COI gene at the mitochondrial DNA. These new
      markers together with a faster method for species verification will allow further
      detailed studies to characterize and compare genetic diversity of historic and
      contemporary C. brachyrhynchos populations.

PMID- 22982160
TI  - Complete genetic characterization of human G2P[6] and G3P[6] rotavirus strains.
AB  - During the 2008-2009 rotavirus season, 10 G3P[6] rotavirus strains were isolated
      for the first time in Belgium, while an outbreak of G2P[6] strains occurred in
      the USA in 2005-2006. Partial sequencing of the 11 genome segments of the 10
      Belgian G3P[6] strains revealed a clonal origin. Two of these strains, and a
      G2P[6] strain representative of the American outbreak, were selected and
      sequenced completely to analyze their evolutionary relationships. Genetic
      analysis revealed that all strains possessed a DS-1-like genotype constellation.
      The 2 Belgian G3P[6] strains showed >99% sequence identity at the nucleotide
      level and the American G2P[6] strain was phylogenetically closely related to the
      Belgian P[6] strains. These data suggest that reassortment(s) involving VP7
      occurred recently, and that the prevalence of DS-1-like P[6] rotavirus strains
      need to be closely monitored because the currently licensed RVA vaccines contain
      neither the P[6] genotype nor strains with a complete human DS-1 genotype
      constellation.

PMID- 22982162
TI  - The use of evidence-based outcomes in systems and organizations providing
      services and supports to persons with intellectual disability.
AB  - This article describes how evidence-based outcomes (EBOs) can be used to improve
      clinical, managerial, and policy decisions. As a component of evidence-based
      practices, EBOs are defined as measures obtained from the assessment of quality
      of life-related indicators that are based on a cross-culturally validated quality
      of life conceptual and measurement model, have utility in that they can be used
      for multiple purposes, and have robustness in reference to reliability and
      validity of the assessment strategy employed. A 5-component EBO model is
      described that provides a framework for the activities involved in selecting,
      developing, and implementing evidence-based outcomes. Three international
      examples based on the reliable, valid, and standardized assessment of individual
      quality of life outcomes are presented that demonstrate how EBOs can be used to
      improve clinical, managerial, and policy decision making. The article concludes
      with a discussion of guidelines for developing and using EBOs, and the challenges
      involved in their use.

PMID- 22982161
TI  - Population genetics of the malaria vector Anopheles aconitus in China and
      Southeast Asia.
AB  - Anopheles aconitus is a well-known vector of malaria and is broadly distributed
      in the Oriental Region, yet there is no information on its population genetic
      characteristics. In this study, the genetic differentiation among populations was
      examined using 140 mtDNA COII sequences from 21 sites throughout Southern China,
      Myanmar, Vietnam, Thailand, Laos and Sri Lanka. The population in Sri Lanka has
      characteristic rDNA D3 and ITS2, mtDNA COII and ND5 haplotypes, and may be
      considered a distinct subspecies. Clear genetic structure was observed with
      highly significant genetic variation present among population groups in Southeast
      Asia. The greatest genetic diversity exists in Yunnan and Myanmar population
      groups. All population groups are significantly different from one another in
      pairwise Fst values, except Northern Thailand with Central Thailand. Mismatch
      distributions and extremely significant F(s) values suggest that the populations
      passed through a recent demographic expansion. These patterns are discussed in
      relation to the likely biogeographic history of the region and compared to other
      Anopheles species.

PMID- 22982163
TI  - The influence of self-assembling supramolecular structures on the passive
      membrane transport of ion-paired molecules.
AB  - Weak ion-ion interactions, such as those associated with ion-pair formation, are
      difficult to isolate and characterise in the liquid state, but they have the
      potential to alter significantly the physicochemical behaviour of molecules in
      solution. The aim of this work was to gain a better understanding of how ion-ion
      interactions influenced passive membrane transport. The test system was composed
      of propylene (PG) glycol, water and diclofenac diethylamine (DDEA). Infrared
      spectroscopy was employed to determine the nature of the DDEA ion-pair
      interactions and the drug-vehicle association. Passive transport was assessed
      using homogeneous synthetic membranes. Solution-state analysis demonstrated that
      the ion-pair was unperturbed by vehicle composition changes, but the solvent-DDEA
      interactions were modified. DDEA-PG/water hydrogen bonding influenced the ion
      pair solubility (X(dev)) and the solvent interactions slowed transport rate in PG
      rich vehicles (0.84+/-0.05 MUg cm(-2) h(-1), at ln(X(dev))=0.57). In water-rich
      co-solvents, the presence of strong water structuring facilitated a significant
      increase (p<0.05) in transmembrane penetration rate (e.g. 4.33+/-0.92 MUg cm(-2)
      h(-1), at ln(X(dev))=-0.13). The data demonstrates that weak ion-ion interactions
      can result in the embedding of polar entities within a stable solvent complex and
      spontaneous supramolecular assembly should be considered when interpreting
      transmembrane transport processes of ionic molecules.

PMID- 22982164
TI  - Development of oral taste masked diclofenac formulations using a taste sensing
      system.
AB  - To achieve patient compliance, organoleptic aspects of drug substances play a key
      role in the development of oral pharmaceutical preparations. In this study, the
      ability of an electronic tongue to help in selecting a drug candidate and
      rationalize the development of oral taste masked formulations was evaluated. As
      drug, diclofenac, in the form of acid, sodium salt and potassium salt, was used.
      The taste sensing system Insent TS-5000Z was capable of differentiating
      diclofenac acid from its salts; and also distinguishing sodium and potassium
      salts eliciting similar taste modalities. Differences between qualities and
      intensities of sensor responses were mainly attributed to the different cations.
      Fewer taste and aftertaste stimuli were recorded for diclofenac acid. Based on
      this screening, the acid form was selected to formulate different diclofenac oral
      taste masked preparations further evaluated using electronic tongue data by
      comparing formulation prototypes against corresponding placebos. Output
      information demonstrated the ability of the taste sensors to detect and
      discriminate different formulation concepts and taste masking strategies.
      Comparative dissolution studies showed insufficient discrimination of formulation
      prototypes. Supported by these results, the electronic tongue proved to be a
      valuable additional tool for assessing and predicting the taste of active
      pharmaceutical ingredients in the early development stage.

PMID- 22982165
TI  - Interaction and destabilization of a monoclonal antibody and albumin to surfaces
      of varying functionality and hydrophobicity.
AB  - Protein products come into contact with many surfaces of differing wettability
      during bioprocessing, formulation and delivery, but corresponding data for the
      adsorbed conformations and the associated force of adhesion (F(ad)) is sparse.
      Here we have generated a series of hydrophilic and hydrophobic surfaces through
      silanization of silica with various terminal groups, characterizing the surface
      energies and droplet contact angles. F(ad) measured by atomic force microscopy
      for oriented monolayers of a human monoclonal antibody (mAb-1) clearly
      distinguished hydrophobic surfaces (low F(ad) values) from hydrophilic surfaces
      (high F(ad) values). High F(ad) for a methoxy capped polyethylene glycol (1000
      MW) surface supports the interaction of mAb-1 with buried ethylene oxide groups,
      consistent with mAb-1 compression into a distorted brush border. Solid state
      circular dichroism showed that mAb-1 (beta-sheet) or albumin (alpha-helical)
      adsorbed to bare silica beads largely retained their secondary structures.
      However, the extent of structural loss upon protein adsorption to functionalized
      silica beads could not be simply correlated to hydrophilic/hydrophobic surface
      interaction as seen for the F(ad) measurements. For example, of the hydrophilic
      surfaces mAb-1 unfolded notably more when adsorbed to the aminopropyl surface,
      and of the hydrophobic surfaces both mAb-1 and albumin retained most secondary
      structure when adsorbed to the perfluorooctyl surface (consistent with the
      lipophobic perfluorinated moiety limiting exposure of the protein hydrophobic
      core). The data show that F(ad) values are not necessarily predictive of the
      subsequent extent of structural relaxation, and that significant structural loss
      is evident for proteins adsorbed to both hydrophilic and hydrophobic surfaces.

PMID- 22982166
TI  - Real time and non-destructive analysis of tablet coating thickness using acoustic
      microscopy and infrared diffuse reflectance spectroscopy.
AB  - Tablet coating thicknesses were estimated using several techniques such as weight
      gain and scanning electron microscopy (SEM), in comparison with acoustic
      microscopy and diffuse reflectance spectroscopy. Acoustic microscopy, used for
      the first time in such an application, is based on the physical phenomenon of
      ultrasound propagation through the materials and the echoes generated by their
      interfaces. Based on the time of flights (TOFs) of the echoes from the coating
      surface and the tablet, it is possible to calculate the coating thickness. In
      order to evaluate the accuracy and robustness of these methods, drug tablets were
      coated with Kollicoat SR polymer for several times, so that to prepare tablets
      with different coating thicknesses. Tablets with 3, 6 and 9 wt% coating material
      have been prepared and based on SEM micrographs it was found that the tablet
      coating thickness is 71.99 +/- 1.2 MUm, 92.5 +/- 1.7 MUm and 132.3 +/- 2.1 MUm,
      respectively (SEM analysis). The tablet coating thicknesses measured with
      acoustic microscopy and infrared diffuse reflectance spectroscopy, were in
      agreement with those obtained using SEM. This verifies that both techniques can
      be successfully applied for real time and non-destructive thickness measurements
      of tablet coating. Furthermore, both techniques, compared with SEM and weight
      gained measurements, are fast and fully automated.

PMID- 22982167
TI  - Production of functional antibody fragments in a vesicle-based eukaryotic cell
      free translation system.
AB  - Cell-free protein synthesis is of increasing interest for the rapid and high
      throughput synthesis of many proteins, in particular also antibody fragments. In
      this study, we present a novel strategy for the production of single chain
      antibody fragments (scFv) in a eukaryotic in vitro translation system. This
      strategy comprises the cell-free expression, isolation and label-free interaction
      analysis of a model antibody fragment synthesized in two differently prepared
      insect cell lysates. These lysates contain translocationally active microsomal
      structures derived from the endoplasmic reticulum (ER), allowing for
      posttranslational modifications of cell-free synthesized proteins. Both types of
      these insect cell lysates enable the synthesis and translocation of scFv into ER
      derived vesicles. However, only the one that has a specifically adapted redox
      potential yields functional active antibody fragments. We have developed a new
      methodology for the isolation of functional target proteins based on the
      translocation of cell-free produced scFv into microsomal structures and
      subsequent collection of protein-enriched vesicles. Antibody fragments that have
      been released from these vesicles are shown to be well suited for label-free
      binding studies. Altogether, these results show the potential of insect cell
      lysates for the production, purification and selection of antibody fragments in
      an easy-to-handle and time-saving manner.

PMID- 22982168
TI  - Improving the thermostability of lipase Lip2 from Yarrowia lipolytica.
AB  - Yarrowia lipolytica lipase Lip2 (YlLip2) is a highly versatile biocatalyst.
      However, its practical use is often hampered by its low stability. Here three
      complementary protein engineering strategies were used to improve the
      thermostability of this enzyme. The first strategy was error-prone PCR based
      directed evolution, which resulted in a YlLip2 variant with a 2.5-fold longer
      half-life of thermal inactivation at 50 degrees C compared to the wild-type
      enzyme. The second strategy was semi-rational design using the so-called B-factor
      iterative test (B-FIT), which led to the discovery of two thermostable YlLip2
      variants that showed a half-life of thermal inactivation 2-fold and 5-fold longer
      than that of the wild-type enzyme, respectively, at 50 degrees C. The third
      strategy was to use site-directed mutagenesis to combinatorially combine all
      three thermostabilizing mutations identified in the first two strategies, which
      improved the half-life of thermal inactivation of YlLip2 by 7-fold compared to
      that of the wild-type enzyme. Such engineered lipases provide not only new
      insights on the protein structure and function relationship but also potentially
      useful catalysts for practical applications.

PMID- 22982169
TI  - Ground gamma-ray survey of the Solforata gas discharge area, Alban Hills-Italy: a
      comparison between field and laboratory measurements.
AB  - Measurements of environmental radioactivity by HPGe gamma-spectrometry were
      carried out with the aim of investigating the distribution of natural
      radionuclides in a volcanic area and to compare two different methodologies - an
      in situ gamma-survey of the area and high accuracy laboratory measurements of
      soil samples. Results demonstrate good performance of the in situ technique, also
      confirmed by a correlation analysis between the results obtained by the two
      methodologies. A volcanic gas discharge area was chosen as the test site for the
      presence of natural long-lived radionuclides such as (40)K and (238)U, (235)U and
      (232)Th, and their decay chain members. Clear evidence of (222)Rn degassing in
      the area was confirmed by (226)Ra values measured by the in situ technique.
      Higher (40)K values measured by the in situ technique may be attributed to the
      presence of vegetation in the study area.

PMID- 22982170
TI  - Reaction of glycal derivatives with alcohols in the presence of N
      bromosuccinimide and diphenyldiselenide: preparation of 2-deoxy-2-phenylselenyl
      glycosides.
AB  - Reaction of glycal derivatives with alcohols or glycosyl acceptors in the
      presence of N-bromosuccinimide (NBS) and diphenyldiselenide resulted in the
      formation of alkyl 2-deoxy-2-phenylselenyl glycosides or disaccharide derivatives
      in excellent yield. The reactions are reasonably fast and considerable stereo
      selectivity was observed in the preparation of disaccharide derivatives.

PMID- 22982171
TI  - Characterization of a laminaribiose phosphorylase from Acholeplasma laidlawii PG
      8A and production of 1,3-beta-D-glucosyl disaccharides.
AB  - We identified a glycoside hydrolase family 94 homolog (ACL0729) from Acholeplasma
      laidlawii PG-8A as a laminaribiose (1,3-beta-D-glucobiose) phosphorylase (EC
      2.4.1.31). The recombinant ACL0729 produced in Escherichia coli catalyzed
      phosphorolysis of laminaribiose with inversion of the anomeric configuration in a
      typical sequential bi bi mechanism releasing alpha-D-glucose 1-phosphate and D
      glucose. Laminaritriose (1,3-beta-D-glucotriose) was not an efficient substrate
      for ACL0729. The phosphorolysis is reversible, enabling synthesis of 1,3-beta-D
      glucosyl disaccharides by reverse phosphorolysis with strict regioselectivity
      from alpha-D-glucose 1-phosphate as the donor and suitable monosaccharide
      acceptors (D-glucose, 2-deoxy-D-arabino-hexopyranose, D-xylose, D-glucuronic
      acid, 1,5-anhydro-D-glucitol, and D-mannose) with C-3 and C-4 equatorial hydroxyl
      groups. The D-glucose and 2-deoxy-D-arabino-hexopyranose caused significantly
      strong competitive substrate inhibition compared with other glucobiose
      phosphorylases reported, in which the acceptor competitively inhibited the
      binding of the donor substrate. By contrast, none of the examined disaccharides
      served as acceptor in the synthetic reaction.

PMID- 22982172
TI  - Synthetic studies on glycosphingolipids from protostomia phyla: synthesis of
      glycosphingolipids and related carbohydrate moieties from the parasite
      Schistosoma mansoni.
AB  - Stereocontrolled syntheses of three neutral glycosphingolipids and six
      oligosaccharide derivatives found from the parasite Schistosoma mansoni have been
      accomplished. A pentasaccharide glycosphingolipid beta-D-Galp-(1->4)-[alpha-L
      Fucp-(1->3)]-beta-D-GlcpNAc-(1->3)-beta-D-GalpNAc-(1->4)-beta-D-Glcp-(1<->1)-Cer
      (1), two hexasaccharide glycosphingolipids alpha-L-Fucp-(1->3)-beta-D-Galp-(1->4)
      [alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc-(1->3)-beta-D-GalpNAc-(1->4)-beta-D-Glcp-(1<
      >1)-Cer (2) and beta-D-Galp-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc-(1->3)
      beta-D-GlcpNAc-(1->3)-beta-D-GalpNAc-(1->4)-beta-D-Glcp-(1<->1)-Cer (3), together
      with their non-reducing end tri- and tetrasaccharides, beta-D-Galp-(1->4)-[alpha
      L-Fucp-(1->3)]-beta-D-GlcpNAcOR (4) and alpha-L-Fucp-(1->3)-beta-D-Galp-(1->4)
      [alpha-L-Fucp-(1->3)]-beta-D-GlcpNAcOR (5), were synthesized by block synthesis.
      Moreover, non-reducing end oligosaccharides of schistosomal glycosphingolipids,
      beta-D-GalpNAc-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAcOR (6), alpha-L-Fucp-(1
      >3)-beta-D-GalpNAc-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAcOR (7), alpha-L
      Fucp-(1->3)-beta-D-GalpNAc-(1->4)-[alpha-L-Fucp-(1->2)-alpha-L-Fucp-(1->3)]-beta
      D-GlcpNAcOR (8) and alpha-L-Fucp-(1->3)-beta-D-GalpNAc-(1->4)-[alpha-L-Fucp-(1
      >2)-alpha-L-Fucp-(1->2)-alpha-L-Fucp-(1->3)]-beta-D-GlcpNAcOR (9) [R=2
      (trimethylsilyl)ethyl], were synthesized as probes to explore their diagnostic
      potential to detect schistosomiasis from patients' sera.

PMID- 22982173
TI  - Sildenafil provides sustained neuroprotection in the absence of learning recovery
      following the 4-vessel occlusion/internal carotid artery model of chronic
      cerebral hypoperfusion in middle-aged rats.
AB  - In this study, we tested whether the phosphodiesterase-5 inhibitor sildenafil
      protects against neurodegeneration and facilitates recovery from learning
      deficits examined long after chronic cerebral hypoperfusion (CCH) induced by the
      4-vessel occlusion/internal carotid artery (4-VO/ICA) model in middle-aged rats.
      Male Wistar rats (12-15 months of age) were subjected to permanent 3-stage 4
      VO/ICA with an interstage interval of 4 days. Sildenafil (3 mg/kg, p.o.) was
      administered at one dose per day for 10 days, beginning soon after the first
      occlusion stage. Three months later, learning in a non-food-rewarded, eight-arm
      radial maze task was tested. Learning performance is expressed as the latency to
      find a goal box and the number of reference or working memory errors.
      Histological examination was performed 1-3 days after behavioral testing. In the
      vehicle-treated group, permanent 4-VO/ICA markedly disrupted learning performance
      and caused moderate-to-severe neurodegeneration in the CA1-CA4 subfields of the
      hippocampus (56.2%), dentate gyrus (DG; 19.2%), retrosplenial cortex (RS cortex;
      47.4%), and parietal association cortex (PtA cortex; 38.2%). Sildenafil treatment
      did not prevent 4-VO/ICA-induced learning deficits, whereas neurodegeneration was
      significantly reduced in the CA1-CA4 subfields (30.5%), DG (7.2%), RS cortex
      (11.8%), and PtA cortex (6.5%). Advancing previous findings from our laboratory,
      this study suggests that while sildenafil can provide important neuroprotection
      in different brain regions of middle-aged rats subjected to CCH, such
      histological effect does not translate into cognitive recovery.

PMID- 22982174
TI  - Lupus nephritis: a critical review.
AB  - Lupus nephritis remains one of the most severe manifestations of systemic lupus
      erythematosus associated with considerable morbidity and mortality. A better
      understanding of the pathogenesis of lupus nephritis is an important step in
      identifying more targeted and less toxic therapeutic approaches. Substantial
      research has helped define the pathogenetic mechanisms of renal manifestations
      and, in particular, the complex role of type I interferons is increasingly
      recognized; new insights have been gained into the contribution of immune
      complexes containing endogenous RNA and DNA in triggering the production of type
      I interferons by dendritic cells via activation of endosomal toll-like receptors.
      At the same time, there have been considerable advances in the treatment of lupus
      nephritis. Corticosteroids have long been the cornerstone of therapy, and the
      addition of cyclophosphamide has contributed to renal function preservation in
      patients with severe proliferative glomerulonephritis, though at the cost of
      serious adverse events. More recently, in an effort to minimize drug toxicity and
      achieve equal effectiveness, other immunosuppressive agents, including
      mycophenolate mofetil, have been introduced. Herein, we provide a detailed review
      of the trials that established the equivalency of these agents in the induction
      and/or maintenance therapy of lupus nephritis, culminating in the recent
      publication of new treatment guidelines by the American College of Rheumatology.
      Although newer biologics have been approved and continue to be a focus of
      research, they have, for the most part, been relatively disappointing compared to
      the effectiveness of biologics in other autoimmune diseases. Early diagnosis and
      treatment are essential for renal preservation.

PMID- 22982175
TI  - Quantitative real-time PCR as a sensitive protein-protein interaction
      quantification method and a partial solution for non-accessible autoactivator and
      false-negative molecule analysis in the yeast two-hybrid system.
AB  - Many functional proteomic experiments make use of high-throughput technologies
      such as mass spectrometry combined with two-dimensional polyacrylamide gel
      electrophoresis and the yeast two-hybrid (Y2H) system. Currently there are even
      automated versions of the Y2H system available that can be used for proteome-wide
      research. The Y2H system has the capacity to deliver a profusion of Y2H positive
      colonies from a single library screen. However, subsequent analysis of these
      numerous primary candidates with complementary methods can be overwhelming.
      Therefore, a method to select the most promising candidates with strong
      interaction properties might be useful to reduce the number of candidates
      requiring further analysis. The method described here offers a new way of
      quantifying and rating the performance of positive Y2H candidates. The novelty
      lies in the detection and measurement of mRNA expression instead of proteins or
      conventional Y2H genetic reporters. This method correlates well with the direct
      genetic reporter readouts usually used in the Y2H system, and has greater
      sensitivity for detecting and quantifying protein-protein interactions (PPIs)
      than the conventional Y2H system, as demonstrated by detection of the Y2H false
      negative PPI of RXR/PPARG. Approximately 20% of all proteins are not suitable for
      the Y2H system, the so-called autoactivators. A further advantage of this method
      is the possibility to evaluate molecules that usually cannot be analyzed in the
      Y2H system, exemplified by a VDR-LXXLL motif peptide interaction.

PMID- 22982176
TI  - MicroRNA signatures of iPSCs and endoderm-derived tissues.
AB  - MicroRNAs (miRNAs), small non-coding RNAs that fine-tune gene expression, play
      multiple roles in the cell, including cell fate specification. We have analyzed
      the differential expression of miRNAs during fibroblast reprogramming into
      induced pluripotent stem cells (iPSCs) and endoderm induction from iPSCs upon
      treatment with high concentrations of Activin-A. The reprogrammed iPSCs assumed
      an embryonic stem cell (ESC)-like miRNA signature, marked by the induction of
      pluripotency clusters miR-290-295 and miR-302/367 and conversely the
      downregulation of the let-7 family. On the other hand, endoderm induction in
      iPSCs resulted in the upregulation of 13 miRNAs. Given that the liver and the
      pancreas are common derivatives of the endoderm, analysis of the expression of
      these 13 upregulated miRNAs in hepatocytes and pancreatic islets revealed a
      tendency for these miRNAs to be expressed more in pancreatic islets than in
      hepatocytes. These observations provide insights into how differentiation may be
      guided more efficiently towards the endoderm and further into the liver or
      pancreas. Moreover, we also report novel miRNAs enriched for each of the cell
      types analyzed.

PMID- 22982177
TI  - Evaluating insulin secretagogues in a humanized mouse model with functional human
      islets.
AB  - OBJECTIVE: To develop a rapid, easy and clinically relevant in vivo model to
      evaluate novel insulin secretagogues on human islets, we investigated the effect
      of insulin secretagogues on functional human islets in a humanized mouse model.
      MATERIALS/METHODS: Human islets were transplanted under the kidney capsule of
      streptozotocin (STZ)-induced diabetic mice with immunodeficiency. Human islet
      graft function was monitored by measuring non-fasting blood glucose levels. After
      diabetes was reversed, human islet transplanted mice were characterized
      physiologically by oral glucose tolerance and pharmacologically with clinically
      proven insulin secretagogues, glucagon-like peptide-1 (GLP-1), exenatide,
      glyburide, nateglinide and sitagliptin. Additionally, G protein-coupled receptor
      40 (GPR40) agonists were evaluated in this model. RESULTS: Long-term human islet
      graft survival could be achieved in immunodeficient mice. Oral glucose challenge
      in human islet transplanted mice resulted in an immediate incremental increase of
      plasma human C-peptide, while the plasma mouse C-peptide was undetectable.
      Treatments with GLP-1, exenatide, glyburide, nateglinide and sitagliptin
      effectively increased plasma human C-peptide levels and improved postprandial
      glucose concentrations. GPR40 agonists also stimulated human C-peptide secretion
      and significantly improved postprandial glucose in the human islet transplanted
      mice. CONCLUSIONS: Our studies indicate that a humanized mouse model with human
      islet grafts could mimic the in vivo characteristics of human islets and could be
      a powerful tool for the evaluation of novel insulin secretagogues or other
      therapeutic agents that directly and/or indirectly target human beta cells.

PMID- 22982178
TI  - Donor substrate binding and enzymatic mechanism of human core alpha1,6
      fucosyltransferase (FUT8).
AB  - BACKGROUND: Fucosylation is essential for various biological processes including
      tumorigenesis, inflammation, cell-cell recognition and host-pathogen
      interactions. Biosynthesis of fucosylated glycans is accomplished by
      fucosyltransferases. The enzymatic product of core alpha1,6-fucosyltransferase
      (FUT8) plays a major role in a plethora of pathological conditions, e.g. in
      prognosis of hepatocellular carcinoma and in colon cancer. Detailed knowledge of
      the binding mode of its substrates is required for the design of molecules that
      can modulate the activity of the enzyme. METHODS: We provide a detailed
      description of binding interactions of human FUT8 with its natural donor
      substrate GDP-fucose and related compounds. GDP-Fuc was placed in FUT8 by
      structural analogy to the structure of protein-O-fucosyltransferase (cePOFUT) co
      crystallized with GDP-Fuc. The epitope of the donor substrate bound to FUT8 was
      determined by STD NMR. The in silico model is further supported by experimental
      data from SPR binding assays. The complex was optimized by molecular dynamics
      simulations. RESULTS: Guanine is specifically recognized by His363 and Asp453.
      Furthermore, the pyrophosphate is tightly bound via numerous hydrogen bonds and
      contributes affinity to a major part. Arg365 was found to bind both the beta
      phosphate and the fucose moiety at the same time. CONCLUSIONS: Discovery of a
      novel structural analogy between cePOFUT and FUT8 allows the placement of the
      donor substrate GDP-Fuc. The positioning was confirmed by various experimental
      and computational techniques. GENERAL SIGNIFICANCE: The model illustrates details
      of the molecular basis of substrate recognition for a human fucosyltransferase
      for the first time and, thus, provides a basis for structure-based design of
      inhibitors.

PMID- 22982180
TI  - The non-neuronal cholinergic system as novel drug target in the airways.
AB  - The parasympathetic nervous system is a key regulator of the human organism
      involved in the pathophysiology of various disorders through cholinergic
      mechanisms. In the lungs, acetylcholine (ACh) released by vagal nerve endings
      stimulates muscarinic receptors thereby increasing airway smooth muscle tone.
      Contraction of airway smooth muscle cells leads to increased respiratory
      resistance and dyspnea. An additional branch of the cholinergic system is the non
      neuronal cholinergic system expressed in nearly all cell types present in the
      airways. Activation of this system may contribute to an increased cholinergic
      tone in the lungs, inducing pathophysiological processes like inflammation,
      remodeling, mucus hypersecretion and chronic cough. Selective muscarinic receptor
      antagonists specifically inhibit acetylcholine at the receptor inducing
      bronchodilation in patients with obstructive airway diseases. This paper reviews
      preclinical pharmacological research activities on anticholinergics including
      experimental models of asthma and chronic obstructive pulmonary disease, COPD. It
      discloses various options to follow up the non-neuronal cholinergic system as a
      novel drug target for the treatment of key aspects of obstructive airway
      diseases, in particular those of a chronic nature.

PMID- 22982181
TI  - Co-expression of estrogen receptor beta and aromatase in Japanese lung cancer
      patients: gender-dependent clinical outcome.
AB  - AIM: The potential gender differences in lung cancer development have been
      proposed on the basis of hormonal actions. We aimed to evaluate whether estrogen
      receptors (ERs) in non-small cell carcinoma (NSCLC) patients may primarily depend
      upon intratumoral estrogen produced via aromatase pathway. MAIN METHODS: We
      evaluated ER beta (ERbeta) and aromatase status in 169 Japanese NSCLC patients
      through immunohistochemistry analysis (IHC). Significance of IHC was further
      confirmed in NSCLC cell lines via in vitro assays. KEY FINDINGS: IHC analysis of
      NSCLC patients demonstrated that both ERbeta and aromatase were highly co
      expressed (p=0.032) in carcinoma cells. Overall survival in males was
      significantly worse than that in postmenopausal female among double positive
      NSCLC patients (p=0.010) but not in non-double positive patients. In addition,
      among double positive cases, overall survival of males was significantly worse
      than that of postmenopausal females in those with higher ERbeta Allred score >=5,
      (p=0.034), but not in those with lower ERbeta Allred score=3-4. In-vitro analysis
      demonstrated aromatase activity on testosterone treatment, which resulted in in
      situ estrogen production (p<0.0001) and increased proliferation of ERbeta
      overexpressing A549 cells (p<0.0001). Aromatase inhibitor i.e. letrozole
      abrogated this proliferation and also enhanced the androgenic activity
      (p<0.0001). Testosterone treatment resulted in estrogen responsive elements
      activation (p<0.0001) in ERbeta vector transfected A549 and LK87 cells whereas ER
      blocker i.e. fulvestrant abrogated this effect, (p<0.0001). SIGNIFICANCE: Our
      results suggest that co-expression of ERbeta and aromatase in NSCLCs of Japanese
      males may result in tumor progression and potential endocrine therapy may confer
      therapeutic benefits to these patients.

PMID- 22982182
TI  - Ginsenoside Rg1 attenuates tau phosphorylation in SK-N-SH induced by Abeta
      stimulated THP-1 supernatant and the involvement of p38 pathway activation.
AB  - AIM: In the present study we aimed to investigate the neuroprotective effect of
      ginsenoside Rg1 (GRg1) on neuronal damage examined in an adopted in vitro
      inflammatory neurodegeneration model and the involvement of p38 MAPK signal
      pathway. MAIN METHODS: The supernatant from Abeta(1-40)-stimulated THP-1
      monocytes was used as culture medium for SK-N-SH neuroblastoma cells which was
      used as target neuronal cells. The cell viability of SK-N-SH cells was assessed
      by detecting lactate dehydrogenase (LDH) leakage; the content of pro-inflammatory
      cytokine was measured by radioimmunoassay; the expressions of tau
      phosphorylation, p-38 and synaptophysin (SYN) were evaluated by western blot
      assay. The microtubule associated protein-2 (MAP-2) expression was confirmed by
      immunostaining. KEY FINDINGS: Our results showed that incubation of the
      supernatant from Abeta(1-40)-stimulated THP-1 cells with SK-N-SH neuroblastoma
      cells for 24h significantly increased LDH leakage, tau and p-38 phosphorylation
      in SK-N-SH cells with increased interleukin (IL)-1beta release into the
      supernatant of THP-1 cells. Pretreatment of THP-1 cells with GRg1 (50, 100 and
      150MUM) for 30min before Abeta(1-40)-stimulation inhibited THP-1 cell-mediated
      Abeta neurotoxicity towards SK-N-SH neuroblastoma and also decreased IL-1beta
      release into THP-1 supernatant dose-dependently. An inhibitor of p38 MAPK,
      SB203580, had the same effect. SIGNIFICANCE: These results suggested that
      activation of the p38 cell signal pathway may be involved in monocyte-mediated
      Abeta neurotoxicity towards SK-N-SH cells. Data obtained from this study
      demonstrated that GRg1 represented a potential treatment strategy for Alzheimer's
      disease (AD).

PMID- 22982183
TI  - Similar efficacies of biliary, with or without pancreatic, sphincterotomy in
      treatment of idiopathic recurrent acute pancreatitis.
AB  - BACKGROUND & AIMS: The role of sphincter of Oddi manometry (SOM) in the
      management of patients with idiopathic recurrent acute pancreatitis requires
      clarification. We evaluated the therapeutic effects of endoscopic sphincterotomy
      in patients with recurrent acute pancreatitis and the prognostic significance of
      pancreatic sphincter dysfunction (SOD). METHODS: We performed a randomized trial
      of endoscopic retrograde cholangiopancreatography with SOM for patients with
      idiopathic recurrent acute pancreatitis. Patients with pancreatic SOD (n = 69)
      were assigned randomly to groups that received only biliary sphincterotomy (BES)
      or a combination of biliary and pancreatic sphincterotomy (DES); patients who
      underwent normal SOM (n = 20) were assigned randomly to groups that received BES
      or a sham surgery. The primary outcome was incidence of recurrent acute
      pancreatitis during the follow-up period (minimum, 1 year; maximum, 10 years). We
      also determined the incidence of chronic pancreatitis and analyzed factors
      associated with recurrence of acute pancreatitis. RESULTS: Among the 69 patients
      with SOD, 48.5% who received BES and 47.2% who received DES had recurrent acute
      pancreatitis (95% confidence interval, -22.3 to 24.9; P = 1.0). In patients with
      normal SOM (n = 20), 27.3% of those who received BES and 11.1% of those who
      received the sham surgery had recurrent acute pancreatitis (95% confidence
      interval, -49.5 to 17.2; P = .59). Overall, 16.9% of subjects developed chronic
      pancreatitis during a median follow-up period of 78 months (interquartile range,
      35-108 mo). The odds of recurrent acute pancreatitis during follow-up evaluation
      were significantly greater among patients with SOD than those with normal SOM
      (unadjusted hazard ratio, 3.5; 95% confidence interval, 1.07-11.4; P < .04), and
      remained so after adjusting for potential confounders (hazard ratio, 4.3; 95%
      confidence interval, 1.3-14.5; P < .02). CONCLUSIONS: Among patients with
      pancreatic SOD, DES and BES have similar effects in preventing recurrence of
      acute pancreatitis. Pancreatic SOD is an independent prognostic factor,
      identifying patients at higher risk for recurrent acute pancreatitis. CLINICAL
      TRIALS REGISTRATION: Clinicaltrials.gov (NCT01583517).

PMID- 22982184
TI  - Teduglutide reduces need for parenteral support among patients with short bowel
      syndrome with intestinal failure.
AB  - BACKGROUND & AIMS: Teduglutide, a glucagon-like peptide 2 analogue, might restore
      intestinal structural and functional integrity by promoting growth of the mucosa
      and reducing gastric emptying and secretion. These factors could increase fluid
      and nutrient absorption in patients with short bowel syndrome with intestinal
      failure (SBS-IF). We performed a prospective study to determine whether
      teduglutide reduces parenteral support in patients with SBS-IF. METHODS: We
      performed a 24-week study of patients with SBS-IF who were given subcutaneous
      teduglutide (0.05 mg/kg/d; n = 43) or placebo (n = 43) once daily. Parenteral
      support was reduced if 48-hour urine volumes exceeded baseline values by >= 10%.
      The primary efficacy end point was number of responders (patients with >20%
      reduction in parenteral support volume from baseline at weeks 20 and 24).
      RESULTS: There were significantly more responders in the teduglutide group (27/43
      [63%]) than the placebo group (13/43 [30%]; P = .002). At week 24, the mean
      reduction in parenteral support volume in the teduglutide group was 4.4 +/- 3.8
      L/wk (baseline 12.9 +/- 7.8 L/wk) compared with 2.3 +/- 2.7 L/wk (baseline 13.2
      +/- 7.4 L/wk) in the placebo group (P < .001). The percentage of patients with a
      1-day or more reduction in the weekly need for parenteral support was greater in
      the teduglutide group (21/39 [54%]) than in the placebo group (9/39 [23%]; P =
      .005). Teduglutide increased plasma concentrations of citrulline, a biomarker of
      mucosal mass. The distribution of treatment-emergent adverse events that led to
      study discontinuation was similar between patients given teduglutide (n = 2) and
      placebo (n = 3). CONCLUSIONS: Twenty-four weeks of teduglutide treatment was
      generally well tolerated in patients with SBS-IF. Treatment with teduglutide
      reduced volumes and numbers of days of parenteral support for patients with SBS
      IF; ClinicalTrials.gov Number, NCT00798967.

PMID- 22982186
TI  - Measuring behaviour in rodents: towards translational neuropsychiatric research.
AB  - Rodent behavioural tasks are indispensable to advance the understanding of gene *
      environment interactions in neuropsychiatric disorders and the discovery of new
      therapeutic strategies. Yet, the actual translation of rodent data to humans, and
      thereby the understanding of the pathophysiology of neuropsychiatric disorders is
      limited. The main reason for the translational flaw is that many behavioural
      tasks for rodents are based on face or predictive validity, whereas these types
      of validity often lack a pathophysiological basis. Furthermore, many behavioural
      tasks for rodents do not implement human task parameters or use task parameters
      in a controlled manner, whereas they are parameters that provide the
      environmental challenges to test gene function. The aim of this perspective is to
      address the status quo of behavioural tasks for rodents, their limitations and
      their strengths, and the reasons why they could lead to suboptimal translational
      research. I also suggest an approach to come closer to neuropsychiatric
      behavioural tasks for rodents, namely a more careful implementation of human task
      parameters and subdivision of behaviour into perceptional, motivational,
      activational and switching domains. Finally, I will touch upon behavioural tasks
      for rodents that are currently lacking and needed to catch up neuropsychiatric
      research.

PMID- 22982185
TI  - GABAB receptor activation attenuates the stimulant but not mesolimbic dopamine
      response to ethanol in FAST mice.
AB  - Neural processes influenced by gamma-aminobutyric acid B (GABA(B)) receptors
      appear to contribute to acute ethanol sensitivity, including the difference
      between lines of mice bred for extreme sensitivity (FAST) or insensitivity (SLOW)
      to the locomotor stimulant effect of ethanol. One goal of the current study was
      to determine whether selection of the FAST and SLOW lines resulted in changes in
      GABA(B) receptor function, since the lines differ in sensitivity to the GABA(B)
      receptor agonist baclofen and baclofen attenuates the stimulant response to
      ethanol in FAST mice. A second goal was to determine whether the baclofen-induced
      reduction in ethanol stimulation in FAST mice is associated with an attenuation
      of the mesolimbic dopamine response to ethanol. In Experiment 1, the FAST and
      SLOW lines were found to not differ in GABA(B) receptor function (measured by
      baclofen-stimulated [(35)S]GTPgammaS binding) in whole brain or in several
      regional preparations, except in the striatum in one of the two replicate sets of
      selected lines. In Experiment 2, baclofen-induced attenuation of the locomotor
      stimulant response to ethanol in FAST mice was not accompanied by a reduction in
      dopamine levels in the nucleus accumbens, as measured by microdialysis. These
      data suggest that, overall, GABA(B) receptor function does not play an integral
      role in the genetic difference in ethanol sensitivity between the FAST and SLOW
      lines. Further, although GABA(B) receptors do modulate the locomotor stimulant
      response to ethanol in FAST mice, this effect does not appear to be due to a
      reduction in tonic dopamine signaling in the nucleus accumbens.

PMID- 22982187
TI  - AMPA receptor mediated behavioral plasticity in the isolated rat spinal cord.
AB  - Previous research has demonstrated that the spinal cord is capable of a simple
      form of instrumental learning. Spinally transected rats that receive shock to a
      hind leg in an extended position quickly learn to maintain the leg in a flexed
      position, reducing net shock exposure whenever that leg is flexed. Subjects that
      receive shock independent of leg position (uncontrollable shock) do not exhibit
      an increase in flexion duration and later fail to learn when tested with
      controllable shock (learning deficit). The present study examined the role of the
      ionotropic glutamate receptor alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) in spinal learning. Intrathecal application of the AMPA
      receptor antagonist CNQX disrupted performance of a spinal instrumental learning
      in a dose dependent fashion (Experiment 1). CNQX also disrupted the maintenance
      of the instrumental response (Experiment 2) and blocked the induction of the
      learning deficit (Experiment 3). Intrathecal application of the agonist AMPA had
      a non-monotonic effect, producing a slight facilitation of performance at a low
      dose and disrupting learning at a high concentration (Experiment 4). Within the
      dose range tested, intrathecal application of AMPA did not have a long-term
      effect (Experiment 5). The results suggest that AMPA-mediated transmission plays
      an essential role in both instrumental learning and the induction of the learning
      deficit.

PMID- 22982179
TI  - Role of the retinal vascular endothelial cell in ocular disease.
AB  - Retinal endothelial cells line the arborizing microvasculature that supplies and
      drains the neural retina. The anatomical and physiological characteristics of
      these endothelial cells are consistent with nutritional requirements and
      protection of a tissue critical to vision. On the one hand, the endothelium must
      ensure the supply of oxygen and other nutrients to the metabolically active
      retina, and allow access to circulating cells that maintain the vasculature or
      survey the retina for the presence of potential pathogens. On the other hand, the
      endothelium contributes to the blood-retinal barrier that protects the retina by
      excluding circulating molecular toxins, microorganisms, and pro-inflammatory
      leukocytes. Features required to fulfill these functions may also predispose to
      disease processes, such as retinal vascular leakage and neovascularization, and
      trafficking of microbes and inflammatory cells. Thus, the retinal endothelial
      cell is a key participant in retinal ischemic vasculopathies that include
      diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or
      infection, as occurs in posterior uveitis. Using gene expression and proteomic
      profiling, it has been possible to explore the molecular phenotype of the human
      retinal endothelial cell and contribute to understanding of the pathogenesis of
      these diseases. In addition to providing support for the involvement of well
      characterized endothelial molecules, profiling has the power to identify new
      players in retinal pathologies. Findings may have implications for the design of
      new biological therapies. Additional progress in this field is anticipated as
      other technologies, including epigenetic profiling methods, whole transcriptome
      shotgun sequencing, and metabolomics, are used to study the human retinal
      endothelial cell.

PMID- 22982188
TI  - Keloid disease can be inhibited by antagonizing excessive mTOR signaling with a
      novel dual TORC1/2 inhibitor.
AB  - Keloid disease (KD) is a fibroproliferative lesion of unknown etiopathogenesis
      that possibly targets the PI3K/Akt/mTOR pathway. We investigated whether
      PI3K/Akt/mTOR inhibitor, Palomid 529 (P529), which targets both mammalian target
      of rapamycin complex 1 (mTORC-1) and mTORC-2 signaling, could exert anti-KD
      effects in a novel KD organ culture assay and in keloid fibroblasts (KF).
      Treatment of KF with P529 significantly (P < 0.05) inhibited cell spreading,
      attachment, proliferation, migration, and invasive properties at a low
      concentration (5 ng/mL) and induced substantial KF apoptosis when compared with
      normal dermal fibroblasts. P529 also inhibited hypoxia-inducible factor-1alpha
      expression and completely suppressed Akt, GSK3beta, mTOR, eukaryotic initiation
      factor 4E-binding protein 1, and S6 phosphorylation. P529 significantly (P <
      0.05) inhibited proliferating cell nuclear antigen and cyclin D and caused
      considerable apoptosis. Compared with rapamycin and wortmannin, P529 also
      significantly (P < 0.05) reduced keloid-associated phenotypic markers in KF. P529
      caused tissue shrinkage, growth arrest, and apoptosis in keloid organ cultures
      and substantially inhibited angiogenesis. pS6, pAkt-Ser473, and mTOR
      phosphorylation were also suppressed in situ. P529 reduced cellularity and
      expression of collagen, fibronectin, and alpha-smooth muscle actin (substantially
      more than rapamycin). These pre-clinical in vitro and ex vivo observations are
      evidence that the mTOR pathway is a promising target for future KD therapy and
      that the dual PI3K/Akt/mTOR inhibitor P529 deserves systematic exploration as a
      candidate agent for the future treatment of KD.

PMID- 22982189
TI  - Loss of TIMP-3 promotes tumor invasion via elevated IL-6 production and predicts
      poor survival and relapse in HPV-infected non-small cell lung cancer.
AB  - Human papillomavirus (HPV) 16/18 E6 oncoprotein is expressed in lung tumors and
      is associated with p53 inactivation. The tissue inhibitor of metalloproteinase 3
      (TIMP-3) is essential for limiting inflammation; therefore, we expected that TIMP
      3 loss might induce chronic inflammation, thereby promoting tumor malignancy as
      well as poor survival and relapse in patients with HPV-infected non-small cell
      lung cancer. In this study, the loss of TIMP-3 by loss of heterozygosity and/or
      promoter hypermethylation was more frequent in HPV16/18 E6-positive tumors than
      in E6-negative tumors. To explore the possible underlying mechanism, E6-negative
      TL4 and CL1-0 cells were transfected with an E6 cDNA plasmid. A marked decrease
      in TIMP-3 expression was caused by promoter hypermethylation via increased DNA
      (cytosine-5-)-methyltransferase 1 (DNMT1) expression. Mechanistic studies
      indicated that TIMP-3 loss promoted interleukin-6 (IL-6) production, which led to
      cell invasion and anchorage-independent growth on soft agar plates. Kaplan-Meier
      and Cox regression models showed that patients with low-TIMP-3/high-IL-6 tumors
      had shorter overall survival and relapse-free survival periods when compared with
      patients with high-TIMP-3/low-IL-6 tumors. In summary, loss of TIMP-3 may
      increase IL-6 production via the tumor necrosis factor alpha/nuclear factor
      kappaB axis, thereby promoting tumor malignancy and subsequent relapse and poor
      survival in patients with HPV-infected non-small cell lung cancer.

PMID- 22982190
TI  - Molecular characterization of immunoglobulin gene rearrangements in diffuse large
      B-cell lymphoma: antigen-driven origin and IGHV4-34 as a particular subgroup of
      the non-GCB subtype.
AB  - The pathogenesis of diffuse large B-cell lymphoma (DLBCL) remains partially
      unknown. The analysis of the B-cell receptor of the malignant cells could
      contribute to a better understanding of the DLBCL biology. We studied the
      molecular features of the immunoglobulin heavy chain (IGH) rearrangements in 165
      patients diagnosed with DLBCL not otherwise specified. Clonal IGH rearrangements
      were amplified according to the BIOMED-2 protocol and PCR products were sequenced
      directly. We also analyzed the criteria for stereotyped patterns in all complete
      IGHV-IGHD-IGHJ (V-D-J) sequences. Complete V-D-J rearrangements were identified
      in 130 of 165 patients. Most cases (89%) were highly mutated, but 12 sequences
      were truly unmutated or minimally mutated. Three genes, IGHV4-34, IGHV3-23, and
      IGHV4-39, accounted for one third of the whole cohort, including an
      overrepresentation of IGHV4-34 (15.5% overall). Interestingly, all IGHV4-34
      rearrangements and all unmutated sequences belonged to the nongerminal center B
      cell-like (non-GCB) subtype. Overall, we found three cases following the current
      criteria for stereotyped heavy chain VH CDR3 sequences, two of them belonging to
      subsets previously described in CLL. IGHV gene repertoire is remarkably biased,
      implying an antigen-driven origin in DLBCL. The particular features in the
      sequence of the immunoglobulins suggest the existence of particular subgroups
      within the non-GCB subtype.

PMID- 22982191
TI  - The eukaryotic transcriptional machinery regulates mRNA translation and decay in
      the cytoplasm.
AB  - In eukaryotes, nuclear mRNA synthesis is physically separated from its
      cytoplasmic translation and degradation. Recent unexpected findings have revealed
      that, despite this separation, the transcriptional machinery can remotely control
      the cytoplasmic stages. Key to this coupling is the capacity of the
      transcriptional machinery to "imprint" the transcript with factors that escort it
      to the cytoplasm and regulate its localization, translation and decay. Some of
      these factors are known transcriptional regulators that also function in mRNA
      decay and are hence named "synthegradases". Imprinting can be carried out and/or
      regulated by RNA polymerase II or by promoter cis- and trans-acting elements.
      This article is part of a Special Issue entitled: RNA polymerase II Transcript
      Elongation.

PMID- 22982192
TI  - Single-molecule studies of RNAPII elongation.
AB  - Elongation, the transcriptional phase in which RNA polymerase (RNAP) moves
      processively along a DNA template, occurs via a fundamental enzymatic mechanism
      that is thought to be universally conserved among multi-subunit polymerases in
      all kingdoms of life. Beyond this basic mechanism, a multitude of processes are
      integrated into transcript elongation, among them fidelity control, gene
      regulatory interactions involving elongation factors, RNA splicing or processing
      factors, and regulatory mechanisms associated with chromatin structure. Many
      kinetic and molecular details of the mechanism of the nucleotide addition cycle
      and its regulation, however, remain elusive and generate continued interest and
      even controversy. Recently, single-molecule approaches have emerged as powerful
      tools for the study of transcription in eukaryotic organisms. Here, we review
      recent progress and discuss some of the unresolved questions and ongoing debates,
      while anticipating future developments in the field. This article is part of a
      Special Issue entitled: RNA Polymerase II Transcript Elongation.

PMID- 22982193
TI  - The many roles of the conserved eukaryotic Paf1 complex in regulating
      transcription, histone modifications, and disease states.
AB  - The Paf1 complex was originally identified over fifteen years ago in budding
      yeast through its physical association with RNA polymerase II. The Paf1 complex
      is now known to be conserved throughout eukaryotes and is well studied for
      promoting RNA polymerase II transcription elongation and transcription-coupled
      histone modifications. Through these critical regulatory functions, the Paf1
      complex participates in numerous cellular processes such as gene expression and
      silencing, RNA maturation, DNA repair, cell cycle progression and prevention of
      disease states in higher eukaryotes. In this review, we describe the historic and
      current research involving the eukaryotic Paf1 complex to explain the cellular
      roles that underlie its conservation and functional importance. This article is
      part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22982194
TI  - Mechanism of transcription through a nucleosome by RNA polymerase II.
AB  - Efficient maintenance of chromatin structure during passage of RNA polymerase II
      (Pol II) is critical for cell survival and functioning. Moderate-level
      transcription of eukaryotic genes by Pol II is accompanied by nucleosome
      survival, extensive exchange of histones H2A/H2B and minimal exchange of histones
      H3/H4. Complementary in vitro studies have shown that transcription through
      chromatin by single Pol II complexes is uniquely coupled with nucleosome survival
      via formation of a small intranucleosomal DNA loop (O-loop) containing the
      transcribing enzyme. In contrast, transient displacement and exchange of all core
      histones are observed during intense transcription. Indeed, multiple transcribing
      Pol II complexes can efficiently overcome the high nucleosomal barrier and
      displace the entire histone octamer in vitro. Thus, various Pol II complexes can
      remodel chromatin to different extents. The mechanisms of nucleosome survival and
      displacement during transcription and the role of DNA-histone interactions and
      various factors during this process are discussed. This article is part of a
      Special Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22982196
TI  - Plasmodium falciparum Prp16 homologue and its role in splicing.
AB  - Large numbers of Plasmodium genes have been predicted to have introns. However,
      little information exists on the splicing mechanisms in this organism. Here, we
      describe the DExD/DExH-box containing Pre-mRNA processing proteins (Prps),
      PfPrp2p, PfPrp5p, PfPrp16p, PfPrp22p, PfPrp28p, PfPrp43p and PfBrr2p, present in
      the Plasmodium falciparum genome and characterized the role of one of these
      factors, PfPrp16p. It is a member of DEAH-box protein family with nine collinear
      sequence motifs, a characteristic of helicase proteins. Experiments with the
      recombinantly expressed and purified PfPrp16 helicase domain revealed binding to
      RNA, hydrolysis of ATP as well as catalytic helicase activities. Expression of
      helicase domain with the C-terminal helicase-associated domain (HA2) reduced
      these activities considerably, indicating that the helicase-associated domain may
      regulate the PfPrp16 function. Localization studies with the PfPrp16 GFP
      transgenic lines suggested a role of its N-terminal domain (1-80 amino acids) in
      nuclear targeting. Immunodepletion of PfPrp16p, from nuclear extracts of parasite
      cultures, blocked the second catalytic step of an in vitro constituted splicing
      reaction suggesting a role for PfPrp16p in splicing catalysis. Further we show by
      complementation assay in yeast that a chimeric yeast-Plasmodium Prp16 protein,
      not the full length PfPrp16, can rescue the yeast prp16 temperature-sensitive
      mutant. These results suggest that although the role of Prp16p in catalytic step
      II is highly conserved among Plasmodium, human and yeast, subtle differences
      exist with regards to its associated factors or its assembly with spliceosomes.

PMID- 22982195
TI  - The Spt4-Spt5 complex: a multi-faceted regulator of transcription elongation.
AB  - In all domains of life, elongating RNA polymerases require the assistance of
      accessory factors to maintain their processivity and regulate their rate. Among
      these elongation factors, the Spt5/NusG factors stand out. Members of this
      protein family appear to be the only transcription accessory proteins that are
      universally conserved across all domains of life. In archaea and eukaryotes, Spt5
      associates with a second protein, Spt4. In addition to regulating elongation, the
      eukaryotic Spt4-Spt5 complex appears to couple chromatin modification states and
      RNA processing to transcription elongation. This review discusses the
      experimental bases for our current understanding of Spt4-Spt5 function and recent
      studies that are beginning to elucidate the structure of Spt4-Spt5/RNA polymerase
      complexes and mechanism of Spt4-Spt5 action. This article is part of a Special
      Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22982197
TI  - Transcription-associated quality control of mRNP.
AB  - Although a prime purpose of transcription is to produce RNA, a substantial amount
      of transcript is nevertheless turned over very early in its lifetime. During
      transcription RNAs are matured by nucleases from longer precursors and activities
      are also employed to exert quality control over the RNA synthesis process so as
      to discard, retain or transcriptionally silence unwanted molecules. In this
      review we discuss the somewhat paradoxical circumstance that the retention or
      turnover of RNA is often linked to its synthesis. This occurs via the association
      of chromatin, or the transcription elongation complex, with RNA degradation
      (co)factors. Although our main focus is on protein-coding genes, we also discuss
      mechanisms of transcription-connected turnover of non-protein-coding RNA from
      where important general principles are derived. This article is part of a Special
      Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22982199
TI  - Voxel-based morphometry of disgust proneness.
AB  - This voxel-based morphometry study investigated whether the personality trait
      disgust proneness is associated with gray matter volume (GMV) of distinct brain
      regions implicated in disgust processing. We analyzed brain structural data from
      99 healthy women, who had rated their tendency to experience disgust for
      different disgust domains (offensive food, death, poor hygiene, decay, and body
      secretions). Food-related disgust proneness was positively correlated with insula
      volume. The disgust domains decay and death showed negative correlations with GMV
      of the dorsomedial and the dorsolateral prefrontal cortex (DMPFC, DLPFC). Our
      data implicate that only core disgust shows an association with the GMV of the
      gustatory cortex, whereas the reactivity to other disgust areas is linked with
      cognitive control areas.

PMID- 22982200
TI  - Cerebrospinal fluid S100B levels reflect symptoms of depression in patients with
      non-inflammatory neurological disorders.
AB  - Recent findings document numerous interactions between neuronal and glial systems
      that likely play a role in the pathophysiology of depression. These findings
      suggest that glia-derived neurotrophic protein S100B may play a significant role
      in developing depression. To test the relationship between S100B and depressive
      symptoms we designed cross-sectional clinical study including S100B serum and CSF
      levels in neurological patients with non-inflammatory disorders (NIND), who
      undergone cerebrospinal fluid assessment for diagnostic purposes. The present
      study was focused on psychometric testing of depression (BDI-II), anxiety (SAS)
      and alexithymia (TAS-20), and neurochemical measure of cerebrospinal fluid (CSF)
      and serum levels of S100B in 40 NIND inpatients [mean age 41.67]. The main result
      shows that S100B in CSF is significantly negatively correlated with BDI-II
      (Spearman R=-0.51, p<0.0009) but not with SAS and TAS-20. The finding indicates
      that decreased level of S100B in CSF is related to increased symptoms of
      depression in the NIND patients.

PMID- 22982201
TI  - Mood congruent psychotic symptoms and specific cognitive deficits in carriers of
      the novel schizophrenia risk variant at MIR-137.
AB  - OBJECTIVE: The Schizophrenia Psychiatric Genome-wide Association (GWAS)
      Consortium recently reported on five novel schizophrenia susceptibility loci. The
      most significant finding mapped to a micro-RNA, MIR-137, which may be involved in
      regulating the function of other schizophrenia and bipolar disorder
      susceptibility genes. METHOD: We genotyped 821 patients with confirmed DSM-IV
      diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective
      disorder for the risk SNP (rs1625579) and investigated the clinical profiles of
      risk allele carriers using a within-case design. We also assessed neurocognitive
      performance in a subset of cases (n=399) and controls (n=171). RESULTS: Carriers
      of the risk allele had lower scores for an OPCRIT-derived positive symptom factor
      (p=0.04) and lower scores on a lifetime measure of psychosis incongruity
      (p=0.017). Risk allele carriers also had more cognitive deficits involving
      episodic memory and attentional control. CONCLUSION: This is the first evidence
      that the MIR-137 risk variant may be associated with a specific subgroup of
      psychosis patients. Although the effect of this single SNP was not clinically
      relevant, investigation of the impact of carrying multiple risk SNPs in the MIR
      137 regulatory network on diagnosis and illness profile may be warranted.

PMID- 22982202
TI  - Differential involvement of two cortical masticatory areas in modulation of the
      swallowing reflex in rats.
AB  - To clarify the functional role of cortical descending inputs involved in the
      swallowing reflex, the effect of electrical stimulation of two cortical
      masticatory areas (CMAs: A- and P-area) on rhythmic jaw movements (RJMs) and
      superior laryngeal nerve (SLN)-evoked swallows were studied. RJMs and swallowing
      reflex were elicited by repetitive electrical stimulation of CMAs and the SLN,
      respectively. The electromyographic activities of jaw-closer (masseter), jaw
      opener (digastric), and laryngeal-elevator (thyrohyoid) muscles were recorded to
      identify the RJMs and swallowing reflex. The number of evoked swallows was
      significantly lower, and swallowing interval was significantly longer during A
      area stimulation compared with those without stimulation. Conversely, these
      parameters were not significantly altered during P-area stimulation. The
      inhibition of swallows by A-area stimulation was not affected by an increase in
      sensory input by wooden stick application between upper and lower teeth, or A
      area stimulation preceding SLN stimulation. The present findings suggest that the
      swallowing reflex is inhibited by activation of the A-area, but not the P-area.
      Since no changes in swallows were seen after the increase in intraoral sensory
      input and prior activation of masticatory central pattern generator (CPG),
      swallowing inhibition may be mediated by direct inputs from the A-area or inputs
      via the masticatory CPG into the swallowing CPG.

PMID- 22982203
TI  - Recombinant mycobacterial HSP65 in combination with incomplete Freund's adjuvant
      induced rat arthritis comparable with that induced by complete Freund's adjuvant.
AB  - Complete Freund's adjuvant (CFA) containing the inactivated mycobacterium has
      been conventionally used to induce typical arthritis in rats. In comparison,
      incomplete Freund's adjuvant (IFA), lacking the mycobacterium, can only induce
      less severe arthritis. However, the key components responsible for the
      arthritogenic effect of the whole mycobacterium are rarely known. Although
      mycobacterial heat-shock protein 65 (MHSP65) specific humoral and cellular immune
      responses were detected in rats with arthritis induced by CFA, MHSP65 alone
      cannot induce arthritis. In this study, we replaced the whole mycobacterium in
      CFA with recombinant MHSP65 (rMHSP65), prepared rMHSP65-IFA emulsion by mixing
      rMHSP65 and IFA, and investigated whether rMHSP65-IFA could induce arthritis in
      rats as CFA did. We found that intradermal injection of the rMHSP65-IFA emulsion
      induced arthritic lesions in testing animals to the same degree as those induced
      by CFA, manifested by severe swelling in hind paws, and synovial thickening,
      cartilage erosion and lymphocytes infiltration in ankle joints. Notably, the
      rMHSP65-IFA recipe also induced the production of anti-dsDNA and -rMHSP65
      antibodies in rats. These results thus demonstrate that rMHSP65 can be used to
      substitute the inactivated mycobacteria in CFA to induce typical arthritis in
      rats.

PMID- 22982204
TI  - Identification of novel paramyxoviruses in insectivorous bats of the Southwest
      Indian Ocean.
AB  - Bats are reservoirs for many emerging zoonotic viruses. In this study, we
      screened 197 animals from 15 different bat species of the Southwest Indian Ocean
      for paramyxovirus infection and identified paramyxoviruses in five insectivorous
      bat-species from the Union of the Comoros (3/66), Mauritius (1/55) and Madagascar
      (4/76). Viral isolation was possible via cell culture and phylogenetic analysis
      revealed these viruses clustered in a Morbillivirus-related lineage, with
      relatively high nucleotide sequence similarity to other recently discovered
      insectivorous-bat paramyxoviruses but distinct from those known to circulate in
      frugivorous bats.

PMID- 22982198
TI  - Transcription-associated histone modifications and cryptic transcription.
AB  - Eukaryotic genomes are packaged into chromatin, a highly organized structure
      consisting of DNA and histone proteins. All nuclear processes take place in the
      context of chromatin. Modifications of either DNA or histone proteins have
      fundamental effects on chromatin structure and function, and thus influence
      processes such as transcription, replication or recombination. In this review we
      highlight histone modifications specifically associated with gene transcription
      by RNA polymerase II and summarize their genomic distributions. Finally, we
      discuss how (mis-)regulation of these histone modifications perturbs chromatin
      organization over coding regions and results in the appearance of aberrant,
      intragenic transcription. This article is part of a Special Issue entitled: RNA
      polymerase II Transcript Elongation.

PMID- 22982205
TI  - Cauliflower mosaic virus major inclusion body protein interacts with the aphid
      transmission factor, the virion-associated protein, and gene VII product.
AB  - The Cauliflower mosaic virus (CaMV) gene VI product (P6) is a multifunctional
      protein essential for viral infection. In order to perform its various tasks, P6
      interacts with both viral and host factors, as well as forming electron-dense
      cytoplasmic inclusion bodies. Here we investigate the interactions of P6 with
      three CaMV proteins: P2 (aphid transmission factor), P3 (virion-associated
      protein), and P7 (protein of unknown function). Based on yeast two-hybrid and
      maltose-binding protein pull-down experiments, P6 interacted with all three of
      these CaMV proteins. P2 helps to stabilize P6 inclusion bodies. Although the P2s
      from two CaMV isolates (W260 and CM1841) differ in the ability to stabilize
      inclusion bodies, both interacted similarly with P6. This suggests that inclusion
      body stability may not be dependent on the efficiency of P2-P6 interaction.
      However, neither P2 nor P3 interacted with P7 in yeast two-hybrid assays.

PMID- 22982206
TI  - Verrucarin A sensitizes TRAIL-induced apoptosis via the upregulation of DR5 in an
      eIF2alpha/CHOP-dependent manner.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the
      most promising candidates for new cancer therapeutics. However, resistance to
      TRAIL in some cancers remains a current problem in recent. The protein-folding
      compartment of the endoplasmic reticulum (ER) is particularly sensitive to
      disturbances, which, if severe, may trigger apoptosis. Therefore, we examined
      whether verrucarin A (VA) sensitize TRAIL-induced apoptosis in cancer cells by
      induction of ER stress. We first found that VA induces a major molecule of ER
      stress, CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5
      induction and subsequently increases TRAIL-induced cleavage of caspases and PARP
      in TRAIL-resistant Hep3B cells. Importantly, the transient knockdown using siRNA
      for CHOP abrogated VA-induced DR5 expression and attenuated TRAIL-induced
      apoptosis. Treatment with VA also increased the levels of phosphorylation of
      eukaryotic translation initiation factor-2alpha (eIF2alpha), which is a common
      cellular response of ER stress. Furthermore, salubrinal, a specific eIF2alpha
      phosphorylation-inducing agent, increased CHOP and DR5 expression in the presence
      of VA. In contrast, transfection of mutant-eIF2alpha significantly reversed VA
      induced apoptosis with downregulation of CHOP-dependent DR5 expression.
      Therefore, VA-induced eIF2alpha phosphorylation seemed to be important for CHOP
      and DR5 upregulation and TRAIL-induced apoptosis. In addition, generation of
      reactive oxygen species (ROS) is an effector molecular in sensitization of VA
      induced ER stress. We concluded that VA triggers TRAIL-induced apoptosis by
      eIF2alpha/CHOP-dependent DR5 induction via ROS generation.

PMID- 22982207
TI  - Synthesis and characterization of doxorubicin modified ZnO/PEG nanomaterials and
      its photodynamic action.
AB  - The aim of this study is to investigate a new strategy of combined application of
      ZnO/PEG nanospheres with anticancer drug of doxorubicin (DOX) in photodynamic
      therapy (PDT). We were able to fabricate ZnO/PEG nanospheres as the drug carrier
      of DOX in drug delivery system. The combination of DOX-ZnO/PEG nanocomposites
      induced the remarkable improvement in the anti-tumor activity, which has been
      demonstrated by antibacterial activity, drug release and DNA cleavage study.
      Furthermore, the possible mechanism was explored by optical spectroscopic studies
      and EPR - spin trapping technique. It was noted that the photodynamic activity of
      the non-cytotoxic DOX loaded ZnO/PEG nanocomposite could considerably increase
      cancer cell injury mediated by reactive oxygen species (ROS) under UV
      irradiation. In our observations demonstrated that ZnO/PEG nanosphere could
      obviously increase the intracellular concentration of DOX and enhance its
      potential anti-tumor efficiency, indicating that ZnO/PEG nanosphere could act as
      an efficient drug delivery carrier importing DOX into target cancer cells. Nearly
      91% of loaded drug was released within 26 h of incubation of conjugates in vitro
      in an acidic environment. It suggests that there is an efficient drug release of
      DOX from DOX-ZnO/PEG nanocomposite. DOX loaded on ZnO/PEG nanomaterials showed
      antibacterial activity was more pronounced with Gram-positive than Gram-negative
      bacteria under visible light. DOX-ZnO/PEG nanocomposites were effective against
      HeLa cell lines under in vitro condition and photocleavage of DNA. This result
      indicated that ZnO/PEG nanomaterials can be used as a nanocarrier for drug
      delivery system for PDT.

PMID- 22982208
TI  - Influence of blue light on Streptococcus mutans re-organization in biofilm.
AB  - Our aim was to examine the viability and structure of new biofilm formed by
      Streptococcus mutans that was previously exposed to blue light. S. mutans
      bacteria were grown to form a mature biofilm, that was exposed to blue light
      (wavelengths, 400-500 nm) for 1-10 min (equivalent to 68-680 J/cm(2)). Biofilm
      was dispersed by sonication, and then the suspended bacteria were grown to re
      organize as a new biofilm. Biofilm formation after 2, 4, and 6 h, was examined by
      viable counts and by confocal laser scanning microscopy using live/dead bacterial
      staining. A significant decrease in bacterial viability was found in the 6h
      biofilms formed by bacteria that had been previously exposed to blue light for 7
      or 10 min. Confocal microscopy images showed a decrease in the live/dead
      bacterial ratio after 3-10 min of light exposures. Dead bacteria were mainly at
      the outer layers of the biofilm. Exposure of S. mutans in biofilm to blue light
      affected the re-formation of a new biofilm, showing an increase in the amount of
      dead bacteria. This phenomenon suggests that blue light has a delayed
      antibacterial effect, although it does not interfere with bacterial capability to
      reform an initial biofilm.

PMID- 22982209
TI  - Keratinocyte ATP binding cassette transporter expression is regulated by
      ultraviolet light.
AB  - Many ATP binding cassette (ABC) transporters are important regulators of lipid
      homeostasis and have been implicated in keratinocyte lipid transport. Ultraviolet
      (UV) light exposure is a known epidermal stressor, which amongst other effects
      causes lipid alterations and defective lamellar body biogenesis. To elucidate the
      background of these lipid changes we studied the effect of UVB light on ABC
      transporter expression. The effect of UVB treatment on the levels of 47 known
      human ABC transporter mRNAs was analyzed in normal human epidermal keratinocytes.
      Immunoblots and promoter assays were carried out for ABCA1 and ABCG1. The mRNA
      levels of cholesterol transport regulators ABCA1 and ABCG1 were markedly
      downregulated by UVB, parallel to the lamellar ichthyosis related
      glucosylceramide transporter ABCA12 and the suspected sphingosine-1-phosphate and
      cholesterol sulfate transporter ABCC1. The long but not the short alternative
      splice variant of the ABCF2 was found to be markedly upregulated rapidly after
      UVB irradiation. Immunoblot confirmed ABCA1 and ABCG1 protein downregulation, and
      luciferase assays showed suppression of their promoters by UVB. These proteins
      mostly transport lipids, which account for the integrity of the epidermal
      barrier; therefore our findings on the UVB regulation of ABC transporters may
      explain the appearance of barrier dysfunction after UVB exposure.

PMID- 22982210
TI  - Susceptibilities of the dermatophytes Trichophyton mentagrophytes and T. rubrum
      microconidia to photodynamic antimicrobial chemotherapy with novel
      phenothiazinium photosensitizers and red light.
AB  - Photodynamic antimicrobial chemotherapy (PACT) is a promising alternative to
      conventional chemotherapy that can be used to treat localized mycosis. The
      development of PACT depends on identifying effective and selective PS for the
      different pathogenic species. The in vitro susceptibilities of Trichophyton
      mentagrophytes and Trichophyton rubrum microconidia to PACT with methylene blue
      (MB), toluidine blue O (TBO), new methylene blue N (NMBN), and the novel
      pentacyclic phenothiazinium photosensitizer S137 were investigated. The efficacy
      of each PS was determined based on its minimal inhibitory concentration (MIC).
      Additionally, we evaluated the effect of PACT with NMBN and S137 on the survival
      of the microconidia of both species. S137 showed the lowest MIC. MIC for S137 was
      2.5 MUM both for T. mentagrophytes and T. rubrum, when a light dose of 5 J cm(-2)
      was used. PACT with NMBN (10 MUM and 20 J cm(-2)) resulted in a reduction of 4
      logs in the survival of the T. rubrum and no survivor of T. mentagrophytes was
      observed. PACT with S137 at 1 MUM and 20 J cm(-2) resulted in a reduction of
      approximately 3 logs in the survival of both species. When a S137 concentration
      of 10 MUM was used, no survivor was observed for both species at all light doses
      (5, 10 and 20 J cm(-2)).

PMID- 22982211
TI  - Protective effect of low UVA irradiation against the action of lethal UVA on
      Pseudomonas aeruginosa: role of the relA gene.
AB  - The exposure of Pseudomonas aeruginosa cells to very low UVA fluences induces a
      growth delay, a phenomenon proposed in Escherichia coli as an adaptive mechanism
      related to protection against lethal and mutagenic effects of UVA. This paper
      reports that the treatment with low UVA irradiation fluences protects P.
      aeruginosa PAO1 strain from a subsequent lethal exposure. This phenomenon depends
      on the relA gene, coding for the main (p)ppGpp synthetase, and is unrelated to
      the induction of quorum sensing or catalase activity, two essential factors
      involved in the response of P. aeruginosa to UVA. Cross-protection between
      osmotic stress and UVA is observed when a great protective response to lethal UVA
      is caused by the induction of resistance to osmotic stress. The increase in
      resistance to osmotic shock observed in the pre-irradiated PAO1 strain but not in
      its relA derivative, unable to show photo-protection, leads us to hypothesize
      that the photo-protection could be attributed to an adaptive response to osmotic
      stress. It is concluded that the exposure of P. aeruginosa to low UVA doses
      induces a relA-dependent adaptive response that protects against cell death
      induced by high doses and causes an increase in the resistance to osmotic stress.

PMID- 22982212
TI  - A fluorescence parameter based analysis on the solubilization of carvedilol by
      bile salt media.
AB  - Carvedilol (CVL), a beta-adrenergic receptor, is insoluble under physiological
      conditions and hence its oral administration is difficult. Bile salts are widely
      used as drug delivery media for many hydrophobic drugs. CVL has a strong
      intrinsic fluorescence with a carbazole moiety. When excited at 320 nm, it
      exhibits dual emission at 347 and 357 nm. As the concentration of bile salt is
      increased there is an overall increase in the fluorescence intensity and also the
      ratio of the intensities at 347 and 357 nm (I(1)/I(2)) increases. This indicates
      that the CVL molecule can sense the non-polar nature of bile salts with
      increasing concentrations. It is showed that the new parameter (I(1)/I(2)) can be
      used as an indicative tool in determining the polarity of the medium. The
      increase in fluorescence anisotropy and fluorescence lifetimes is observed,
      indicating the micro-heterogeneity of the bile salt solutions as experienced by
      CVL molecules. The possibility of electrostatic interactions between CVL and bile
      salt micelles is ruled out in view of the results obtained here and their
      interaction is purely hydrophobic in nature. The results suggest that the CVL
      molecule associates with the steroidal moiety of bile salts through its carbazole
      moiety.

PMID- 22982213
TI  - Measurement of urinary catecholamines in small samples for mice.
AB  - INTRODUCTION: Analysis of catecholamines in small samples of urine is difficult
      and sensitive to stress. Current techniques require pooling of samples or
      expensive separation by double mass spectrometry. A method for extraction of
      unconjugated catecholamines in 20MUL urine samples has been developed using
      alumina extraction prior to separation by high performance liquid chromatography
      (HPLC) and electrochemical detection (ECD). METHODS: Three murine experiments
      tested the application of the procedure. In the first, collection occurred in the
      morning and evening prior to handling, and in the morning after three days of
      handling. In the second, passively obtained urine was compared to stressfully
      obtained urine in the same mice. Finally, basal collections were compared to
      urinary catecholamine levels 15 and 30min into novel cage stress. Urine was
      extracted alongside 2,3-dihydroxybenzoic acid (DHBA) internal standard via
      alumina and brought to pH 8.5 with tris buffer. The mixture underwent two wash
      steps for depuration and eluted with perchloric acid for analysis on HPLC with
      ECD. RESULTS: This novel extraction method using low amounts of urine yielded 48%
      recovery in the samples and 60% recovery in the standard extraction on average.
      With a signal to noise ratio of 3:1, the limit of detection (LOD) of a standard
      is 1.2pg/mL, which allows for the detection of 3.6pg/mL in urine or 72fg in a
      20MUL sample. Thus resting catecholamine levels are 216 times higher than the
      LOD. Unconjugated norepinephrine and epinephrine levels were significantly
      increased 15min after novel cage stress and epinephrine remained elevated after
      30min, but did not show significant differences when comparing collection time,
      handling exposure, or specific collection technique. DISCUSSION: The technique is
      an effective measure for sympathetic activity in micro samples, with a limit of
      detection in the attomole range for 20MUL samples.

PMID- 22982214
TI  - Epigenetic changes brought about by perinatal stressors: a brief review of the
      literature.
AB  - INTRODUCTION: Numerous studies employing various animal models have found that
      perinatal stress, encountered in utero during sensitive developmental stages or
      shortly after birth, disrupts both sexual differentiation and sexual behavior in
      offspring. The biochemical, cellular, genetic and epigenetic events which are
      involved in the organismal response to perinatal stress are currently under
      investigation. METHODS, RESULTS AND DISCUSSION: In this review, the reader is
      introduced to perinatal stressors as a toxicological phenomenon, and several
      recently characterized epigenetic responses to said stressors are discussed.

PMID- 22982215
TI  - Mixed lubrication after rewetting of blotted pleural mesothelium.
AB  - Coefficient of kinetic friction (MU) of pleural mesothelium blotted with filter
      paper, and rewetted with Ringer solution markedly increases; this increase is
      removed if a sufficient amount of sialomucin or hyaluronan is added to Ringer
      (Bodega et al., 2012. Respiratory Physiology and Neurobiology 180, 34-39). In
      this research we found that MU of pleural mesothelium blotted, rewetted, and
      sliding at physiological velocities and loads, decreased with increase of
      velocity, mainly at low velocities. Despite this decrease, MU at highest velocity
      was still double that before blotting. With small concentration of sialomucin or
      hyaluronan MU was markedly smaller at each velocity, decreased less with increase
      of velocity, and at highest velocity approached preblotting value. These findings
      indicate a regime of mixed lubrication in post-blotting Ringer, at variance with
      boundary lubrication occurring before blotting or postblotting with sufficient
      macromolecule addition. Greater roughness of mesothelial surface, caused by
      blotting, likely induces zones of elastohydrodynamic lubrication, which increase
      with velocity, while contact area decreases.

PMID- 22982217
TI  - Cellular reprogramming to reset epigenetic signatures.
AB  - The controlled differentiation of induced pluripotent stem cells (iPSC) towards
      clinically-relevant cell types has benefitted from epigenetic profiling of
      lineage-specific markers to confirm the phenotype of iPSC-derived cells. Mapping
      epigenetic marks throughout the genome has identified unique changes which occur
      in the DNA methylation profile of cells as they differentiate to specific cell
      types. Beyond characterizing the development of cells derived from pluripotent
      stem cells, the process of reprogramming cells to iPSC resets lineage-specific
      DNA methylation marks established during differentiation to specific somatic cell
      types. This property of reprogramming has potential utility in reverting aberrant
      epigenetic alterations in nuclear organization that are linked to disease
      progression. Since DNA methylation marks are reset following reprogramming, and
      contribute to restarting developmental programs, it is possible that DNA
      methylation marks associated with the disease state may also be erased in these
      cells. The subsequent differentiation of such cells could result in cell progeny
      that will function effectively as therapeutically-competent cell types for use in
      regenerative medicine. This suggests that through reprogramming it may be
      possible to directly modify the epigenetic memory of diseased cells and help to
      normalize their cellular phenotype, while also broadening our understanding of
      disease pathogenesis.

PMID- 22982216
TI  - Carotid chemoreceptor "resetting" revisited.
AB  - Carotid body (CB) chemoreceptors transduce low arterial O(2) tension into
      increased action potential activity on the carotid sinus nerves, which
      contributes to resting ventilatory drive, increased ventilatory drive in response
      to hypoxia, arousal responses to hypoxia during sleep, upper airway muscle
      activity, blood pressure control and sympathetic tone. Their sensitivity to O(2)
      is low in the newborn and increases during the days or weeks after birth to reach
      adult levels. This postnatal functional maturation of the CB O(2) response has
      been termed "resetting" and it occurs in every mammalian species studied to date.
      The O(2) environment appears to play a key role; the fetus develops in a low O(2)
      environment throughout gestation and initiation of CB "resetting" after birth is
      modulated by the large increase in arterial oxygen tension occurring at birth.
      Although numerous studies have reported age-related changes in various components
      of the O(2) transduction cascade, how the O(2) environment shapes normal CB
      prenatal development and postnatal "resetting" remains unknown. Viewing CB
      "resetting" as environment-driven (developmental) phenotypic plasticity raises
      important mechanistic questions that have received little attention. This review
      examines what is known (and not known) about mechanisms of CB functional
      maturation, with a focus on the role of the O(2) environment.

PMID- 22982218
TI  - The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic
      marks in thyroid cancer cell lines.
AB  - Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide
      symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34
      on several properties of thyroid cancer cell lines was investigated. In TPC1,
      BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels. In
      BCPAP and TPC1 cells also significant increase of radio-iodine uptake was
      induced. Accordingly, in transfection experiments performed in TPC1 cells,
      treatment with PJ34 increased NIS promoter activity without affecting PARP-1
      binding to the promoter sequence. We also investigated the epigenetic status of
      NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase
      of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we
      observed also an increase of H3K27me3, a classical repressive mark. Our data
      demonstrate that in various thyroid cancer cell lines PARP inhibition increases
      NIS gene expression through a particular modulation of transcriptional regulatory
      mechanisms. Therefore, we suggest that PARP inhibitors may deserve future
      investigations as tools for medical treatment of thyroid cancer.

PMID- 22982220
TI  - Dechlorane Plus in serum from e-waste recycling workers: influence of gender and
      potential isomer-specific metabolism.
AB  - Dechlorane Plus (DP) and its dechlorinated product, anti-Cl11-DP, were measured
      in serum of 70 occupationally exposed workers in an e-waste recycling region and
      13 residents of an urban area in South China. The DP levels were significantly
      higher in the workers (22-2200 ng/g with median of 150 ng/g lipid) than in the
      urban residents (2.7-91 ng/g with median of 4.6 ng/g lipid). The DP
      concentrations in females were found to be associated with their age but such
      relation was not found for males. Significant differences in DP levels and DP
      isomer composition were found between genders. The females had remarkably higher
      DP levels and f(anti) values (fraction of anti-DP to total DPs) in serum than the
      males. Anti-Cl11-DP was significantly correlated with anti-DP for both genders
      but with different slope of regression line. The ratios of anti-Cl11-DP to anti
      DP (mean of 0.017) in males were significantly higher than those (mean of 0.010)
      in females. Combining with the lower f(anti) values in males, it is likely that
      males have higher metabolic potential for DPs than females which resulted in the
      lower DP loading in serum. However, the different patterns of selective uptake
      and/or excretion of different compounds between genders cannot be eliminated as a
      possible reason for the observed gender differences. This study is the first to
      report on the gender difference in DP accumulation in human, and its mechanism is
      worth further investigation.

PMID- 22982219
TI  - Gene cloning, expression, and characterization of mutanase from Paenibacillus
      curdlanolyticus MP-1.
AB  - Mutanases hydrolyze d-glucosidic linkages of alpha-1,3-linked polysaccharides
      which are important components of dental plaque. Therefore, these enzymes can be
      useful in preventive oral hygiene. A gene encoding mutanase was cloned from soil
      isolated Paenibacillus curdlanolyticus MP-1 and expressed in Escherichia coli,
      and the resulting recombinant enzyme was characterized. The nucleotide sequence
      of the mutanase gene consisted of 3786 nucleotides encoding a protein of 1261
      amino acids with a theoretical molecular weight of 131.62kDa. The deduced amino
      acid sequence exhibited a high degree of similarity with mutanases of
      Paenibacillus sp. KSM-M126 and Paenibacillus humicus NA1123, with 84% and 80%
      identity, respectively. The recombinant enzyme was purified 17.5-fold to
      homogeneity with a recovery of 37%. The purified mutanase showed optimal activity
      at pH 6.0 and 45 degrees C, and was completely stable at pH 4.0-9.5 and up to 45
      degrees C. The enzyme was specific for alpha-1,3-glucosidic linkages and
      effectively solubilized fungal alpha-1,3-glucans and streptococcal mutans,
      releasing nigerooligosaccharides. The mutanase did not hydrolyze a synthetic
      substrate readily hydrolyzed by exoglucanases and the enzyme activity was not
      suppressed in the presence of deoxynojirimycin, an inhibitor of exo-type enzymes.
      These results suggest an endohydrolytic mode of action.

PMID- 22982221
TI  - Tools to study the degradation and loss of the N-phenyl carbamate chlorpropham--a
      comprehensive review.
AB  - Chlorpropham (CIPC) was introduced in 1951 and is a primary N-phenyl carbamate
      belonging to a group of pesticides known as carbamates which are estimated to
      account for 11% of the total insecticide sales worldwide. They were considered
      less toxic than organochlorines due to their easier breakdown but, subsequent
      concerns regarding the environmental impact and their breakdown products have
      shown them to be environmental toxins and toxic and/or carcinogenic for humans.
      CIPC is used in growing crops to control weeds and also as a sprout suppressant
      on crops during long-term storage and while its degradation has been studied and
      rates quoted these vary greatly. Here published rates of degradation by
      hydrolysis, biolysis, photolysis and thermal processes are reviewed as well as
      data on partitioning in air, water and soil. In addition the details of the
      experimental procedures are reviewed and compared showing how the half-lives and
      partitioning coefficients have been calculated leading to an understanding of how
      such vastly different values are achieved. The legislation regarding the use of
      CIPC and its maximum residue level is also discussed particularly in reference to
      recent European Commission (EC) legislation. In view of the fact that analytical
      data on the breakdown of CIPC play an important role in decision-making by
      regulatory agencies, the authors feel that it is time for an up-to-date review of
      the data available, including very recent developments in methodology.

PMID- 22982222
TI  - Evidence of DNA damage in humans inhabiting a volcanically active environment: a
      useful tool for biomonitoring.
AB  - The present study was designed to evaluate whether chronic exposure to a
      volcanically active environment might result in genotoxic and cytotoxic effects
      in human oral epithelial cells. A study group of 120 individuals inhabiting a
      volcanically active environment (exposed group; Furnas village) and a reference
      group of 122 individuals inhabiting a village without manifestations of volcanic
      activity (Santo Antonio village) were examined in this study. Individuals from
      Furnas village inhabit a volcanically active environment marked by several
      degassing manifestations, including fumarolic fields, thermal and cold CO2
      springs and soil diffuse degassing areas. For each individual, 1000 buccal
      epithelial cells were analyzed for the frequency of micronucleated cells (MNC)
      and the frequency of cells with other nuclear anomalies (ONA: pyknosis,
      karyolysis and karyorrhexis), by using the micronucleus assay. Information on
      life-style factors and an informed consent were obtained from each participant.
      The frequencies of MNC and of ONA per 1000 cells in the exposed group (4.30/00
      and 23.50/00, respectively) were significantly higher than in the reference group
      (1.70/00 and 7.70/00, respectively). The risk of having a high frequency of MNC
      or ONA was 2.4 and 3.1-fold higher in exposed individuals compared to reference
      group. The analyzed confounding factors (age, gender, smoking status, alcohol
      consumption, and mouthwash use) did not show any significant association with the
      frequency of MNC or ONA. The higher risk of DNA damage in individuals inhabiting
      a volcanically active environment is for the first time clearly highlighted with
      this biomonitoring study. Given that MNC in oral epithelia are recognized as a
      predictive biomarker of cancer risk within a population of healthy subjects,
      these findings could contribute to explain the high incidence rates of lip, oral
      cavity and pharynx cancers previously referred for Furnas village inhabitants.

PMID- 22982223
TI  - A novel abbreviation standard for organobromine, organochlorine and
      organophosphorus flame retardants and some characteristics of the chemicals.
AB  - Ever since the interest in organic environmental contaminants first emerged
      50years ago, there has been a need to present discussion of such chemicals and
      their transformation products using simple abbreviations so as to avoid the
      repetitive use of long chemical names. As the number of chemicals of concern has
      increased, the number of abbreviations has also increased dramatically, sometimes
      resulting in the use of different abbreviations for the same chemical. In this
      article, we propose abbreviations for flame retardants (FRs) substituted with
      bromine or chlorine atoms or including a functional group containing phosphorus,
      i.e. BFRs, CFRs and PFRs, respectively. Due to the large number of halogenated
      and organophosphorus FRs, it has become increasingly important to develop a
      strategy for abbreviating the chemical names of FRs. In this paper, a two step
      procedure is proposed for deriving practical abbreviations (PRABs) for the
      chemicals discussed. In the first step, structural abbreviations (STABs) are
      developed using specific STAB criteria based on the FR structure. However, since
      several of the derived STABs are complicated and long, we propose instead the use
      of PRABs. These are, commonly, an extract of the most essential part of the STAB,
      while also considering abbreviations previously used in the literature. We
      indicate how these can be used to develop an abbreviation that can be generally
      accepted by scientists and other professionals involved in FR related work.
      Tables with PRABs and STABs for BFRs, CFRs and PFRs are presented, including CAS
      (Chemical Abstract Service) numbers, notes of abbreviations that have been used
      previously, CA (Chemical Abstract) name, common names and trade names, as well as
      some fundamental physico-chemical constants.

PMID- 22982224
TI  - A methodology for evaluating the influence of diets and intergenerational dietary
      transitions on historic and future human exposure to persistent organic
      pollutants in the Arctic.
AB  - Concentrations of persistent organic pollutants (POPs) in Inuit populations have
      been observed to decrease over the last decade. The main objective of this study
      was to develop a methodology to quantify the potential influence of
      intergenerational dietary transitions on human exposure to organic contaminants
      in the Arctic environment using PCB-153 as a case study. Long-term (1930-2050)
      dynamic simulations using realistic emission estimates were conducted using
      linked chemical fate and bioaccumulation models. Female body burdens were
      calculated over time assuming five diets with varying proportions of traditional
      and imported food items and then used to illustrate the potential variability at
      a community/population level. At any given time point, individuals consuming a
      100% traditional diet (i.e. high intake of ringed seal blubber) have modelled
      body burdens approximately 15-150 times higher than individuals consuming a 100%
      imported food diet. Consumption of locally-harvested fish (e.g. Arctic cod) and
      seal meat are also associated with comparatively low body burdens. Decreased
      emissions are predicted to decrease the PCB-153 body burden of 30-year old
      females by 6 to 13-fold from 1980 to 2020 with dietary transitions accounting for
      an additional factor of 2-50 (i.e. 12-650 times lower in total) depending on the
      type of dietary transition and the origin of the imported food items. The model
      results indicate that dietary transitions are an important factor underlying the
      variability within and between subpopulations in addition to partially explaining
      the observed temporal trends. Specific information on the nature and timing of
      dietary transitions is highly valuable when interpreting biomonitoring data.

PMID- 22982225
TI  - Melatonin may play a role in modulation of bax and bcl-2 expression levels to
      protect rat peripheral blood lymphocytes from gamma irradiation-induced
      apoptosis.
AB  - The close relationship between free radicals effects and apoptosis process has
      been proved. Melatonin has been reported as a direct free radical scavenger. We
      investigated the capability of melatonin in the modification of radiation-induced
      apoptosis and apoptosis-associated upstream regulators expression in rat
      peripheral blood lymphocytes. Rats were irradiated with a single whole body
      Cobalt 60-gamma radiation dose of 8Gy at a dose rate of 101cGy/min with or
      without melatonin pretreatments at different concentrations of 10 and 100mg/kg
      body weight. The rats were divided into eight groups of control, irradiation
      only, vehicle-only, vehicle plus irradiation, 10mg/kg melatonin alone, 10mg/kg
      melatonin plus irradiation, 100mg/kg melatonin alone and 100mg/kg melatonin plus
      irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or
      the same volume of vehicle alone 1h prior to irradiation. Blood samples were
      taken 4, 24, 48 and 72h after irradiation for evaluation of flow cytometric
      analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax
      and bcl-2 expression using quantitative real-time PCR (RT(2)qPCR). Irradiation
      only and vehicle plus irradiation showed an increase in the percentage of
      apoptotic lymphocytes significantly different from control group (P<0.01), while
      melatonin pretreatments in a dose-dependent manner reduced it as compared with
      the irradiation-only and vehicle plus irradiation groups (P<0.01) in all time
      points. This reduced apoptosis by melatonin was related to the downregulation of
      bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our
      results suggest that melatonin in these doses may provide modulation of bax and
      bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood
      lymphocytes from gamma irradiation-induced apoptosis.

PMID- 22982226
TI  - Radioprotective role of H(2)S/CSE pathway in Chang liver cells.
AB  - Radiation-induced liver cell damage may be life-threatening. Here, we
      investigated whether hydrogen sulfide (H(2)S)/cystathionine gamma-lyase (CSE)
      pathway could serve the protective role toward radiation in normal human liver
      cells. Our data showed that pretreatment of cells with H(2)S donor, sodium
      hydrosulfide (NaHS) significantly attenuated radiation induced micronuclei
      formation and improved cell viability. However, the use of dl-propargylglycine
      (PPG), a potent inhibitor of CSE, markedly enhanced the cell-killing effect
      induced by radiation. Exposure of cells to 2Gy gamma-radiation led to significant
      increases of the endogenous H(2)S content. The mRNA and protein expressions of
      CSE also increased after radiation in a time-dependent manner, while the
      expression of cystathionine beta-synthase (CBS), another endogenous H(2)S
      synthetase, did not change significantly. Notably, radiation induced production
      of reactive oxygen species (ROS) was significantly reversed by the pretreatment
      of NaHS, while blockage of CSE activity resulted in an enhanced ROS production in
      irradiated cells. Moreover, NaHS markedly suppressed radiation-induced
      phosphorylation of P53, decrease of Bcl-2/Bax, and activity of nuclear factor
      kappaB (NF-kappaB). In conclusion, our finding demonstrates that H(2)S/CSE
      pathway plays a radioprotection role by inhibiting radiation-induced ROS
      production, P53 phosphorylation, NF-kappaB activation and decrease of Bcl-2/Bax,
      indicating that modulation of H(2)S may be a novel protection strategy for liver
      radiation injury in radiotherapy.

PMID- 22982227
TI  - Identification of amino acid residues essential to the activity of lyase CpcT1
      from Nostoc sp. PCC7120.
AB  - The phycocyanin lyase CpcT1 (encoded by gene all5339) and lyase CpcS1 (encoded by
      gene alr0617) are capable of catalyzing the phycocyanobilin (PCB) covalently
      bound to the different sites of phycocyanin's and phycoerythrocyanin's beta
      subunits, respectively. Lyase CpcS1, whose catalytic mechanism had been
      researched clearly, participates in the covalent coupling of phycobilin and
      apoprotein in the form of chaperone, and its important amino acids have been
      confirmed. In order to identify the functional amino acid residues of CpcT1,
      chemical modification was conducted to arginine, histidine, tryptophan, lysine
      and amino acid carboxyl of CpcT1. The results indicated that the catalytic
      activity of the CpcT1 was changed. After the modification of arginine, tryptophan
      and histidine, site-directed mutations were performed to those highly conserved
      amino acids which were selected by means of homologous comparison. The mutated
      lyase, apoprotein and the enzymes that synthesize the phycobilins were recombined
      in Escherichia coli (E. coli) and in vitro, yielding chromoproteins, which were
      detected by fluorescence and UV absorption spectrometry. The spectra were
      compared with that of the chromoprotein catalyzed by wild type lyase CpcT1,
      achieving relative specific activities of the various mutants. Meanwhile, the
      mutants were expressed in E. coli, and then circular dichroism structure of near
      UV region was determined. The results demonstrated that H33F, W175S, R97A, C137S
      and C116S influence the catalytic activity of CpcT1. Being different from wild
      CpcT1, a great deal of alpha helix was involved in the structure of circular
      dichroism of R97A and W13S. CpcT1 or its mutants and the enzymes that synthesize
      the phycobilins, were reconstituted in E. coli and detected by spectra to check
      the bounding of lyases and PCB. The results of spectra and SDS-PAGE confirm that
      CpcT1 and its mutants cannot bind phycobilin, differing from the catalytic
      mechanism of CpcS1.

PMID- 22982229
TI  - Large-scale production of soluble recombinant amyloid-beta peptide 1-42 using
      cold-inducible expression system.
AB  - Amyloid-beta peptide 1-42 (Abeta(1-42)), the predominant form in senile plaques,
      plays important roles in the pathogenesis of Alzheimer's disease. Because Abeta(1
      42) has aggregation-prone nature, it has been difficult to produce in a soluble
      state in bacterial expression systems. In this study, we modified our expression
      system to increase the soluble fraction of Abeta(1-42) in Escherichia coli (E.
      coli) cells. The expression level and solubility of recombinant Abeta(1-42)
      induced at the low temperature (16 degrees C) is highly increased compared to
      that induced at 37 degrees C. To optimize expression temperature, the coding
      region of Abeta(1-42) was constructed in a pCold vector, pCold-TF, which has a
      hexahistidine-tagged trigger factor (TF). Recombinant Abeta(1-42) was expressed
      primarily as a soluble protein using pCold vector system and purified with a
      nickel-chelating resin. When the toxic effect of recombinant Abeta(1-42) examined
      on human neuroblastoma SH-SY5Y cells, the purified Abeta(1-42) induced cell
      toxicity on SH-SY5Y cells. In conclusion, the system developed in this study will
      provide a useful method for the production of aggregation prone-peptide such as
      Abeta(1-42).

PMID- 22982228
TI  - Endoplasmic reticulum stress induces the expression of COX-2 through activation
      of eIF2alpha, p38-MAPK and NF-kappaB in advanced glycation end products
      stimulated human chondrocytes.
AB  - INTRODUCTION: During aging, advanced glycation end products (AGEs) accumulate in
      articular cartilage. In this study we determined whether AGEs induce endoplasmic
      reticulum (ER) stress and studied the ER stress-activated pathways that stimulate
      cyclooxygenase-2 (COX-2) expression in human chondrocytes. METHODS: Chondrocytes
      were stimulated with AGE-BSA. Gene expression was determined by quantitative PCR
      and protein expression was studied by immunoblotting. Studies to elucidate
      involved pathways were executed using siRNAs and specific inhibitors of
      eukaryotic initiation factor-2alpha (eIF2alpha), MAPKs and NF-kappaB. RESULTS:
      AGE-BSA induced expression of GRP78 with concomitant increase in COX-2 expression
      was observed in human chondrocytes. In addition, expression of Bag-1, an ER
      stress marker was also increased by AGE-BSA. RAGE knockdown inhibited AGE-BSA
      induced expression of GRP78 and COX-2. Treatment with eIF2alpha inhibitor or
      eIF2alpha knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2 with
      decreased PGE(2) production. Treatment with SB202190 inhibited AGE-BSA-induced
      expression of GRP78 and COX-2, while treatment with PD98051 inhibited AGE-BSA
      induced GRP78 protein expression but had no effect on COX-2 protein expression.
      SP600125 had no effect on either GRP78 or COX-2 protein expression. Bay 11-7082
      suppressed AGE-BSA-induced GRP78 and COX-2 expression. AGE-BSA-induced activation
      of NF-kappaB was inhibited by treatment with SB202190 and by eIF2alpha knockdown,
      but was not inhibited when chondrocytes were treated with SP600125 or PD98059.
      CONCLUSION: This study demonstrates that AGEs induce ER stress and stimulate the
      expression of COX-2 through eIF2alpha, p38-MAPK and NF-kappaB pathways in human
      chondrocytes. Our results provide important insights into cartilage degradation
      in osteoarthritis associated with latent ER stress.

PMID- 22982230
TI  - Cloning, expression, purification, and biochemical characterisation of the FIC
      motif containing protein of Mycobacterium tuberculosis.
AB  - The role of FIC (Filamentation induced by cAMP)(2) domain containing proteins in
      the regulation of many vital pathways, mostly through the transfer of NMPs from
      NTPs to specific target proteins (NMPylation), in microorganisms, higher
      eukaryotes, and plants is emerging. The identity and function of FIC domain
      containing protein of the human pathogen, Mycobacterium tuberculosis, remains
      unknown. In this regard, M. tuberculosis fic gene (Mtfic) was cloned,
      overexpressed, and purified to homogeneity for its biochemical characterisation.
      It has the characteristic FIC motif, HPFREGNGRSTR (HPFxxGNGRxxR), spanning 144th
      to 155th residue. Neither the His-tagged nor the GST-tagged MtFic protein,
      overexpressed in Escherichia coli, nor expression of Mtfic in Mycobacterium
      smegmatis, yielded the protein in the soluble fraction. However, the maltose
      binding protein (MBP) tagged MtFic (MBP-MtFic) could be obtained partly in the
      soluble fraction. The cloned, overexpressed, and purified recombinant MBP-MtFic
      showed conversion of ATP, GTP, CTP, and UTP into AMP, GMP, CMP, and UMP,
      respectively. Sequence alignment with several FIC motif containing proteins,
      complemented with homology modeling on the FIC motif containing protein, VbhT of
      Bartonella schoenbuchensis as the template, showed conservation and interaction
      of residues constituting the FIC domain. Site-specific mutagenesis of the His144,
      or Glu148, or Asn150 of the FIC motif, or of Arg87 residue that constitutes the
      FIC domain, or complete deletion of the FIC motif, abolished the NTP to NMP
      conversion activity. The design of NMP formation assay using the recombinant,
      soluble MtFic would enable identification of its target substrate for NMPylation.

PMID- 22982232
TI  - Binaural speech processing in individuals with auditory neuropathy.
AB  - Auditory neuropathy disrupts the neural representation of sound and may therefore
      impair processes contingent upon inter-aural integration. The aims of this study
      were to investigate binaural auditory processing in individuals with axonal
      (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A)
      auditory neuropathy and to evaluate the relationship between the degree of
      auditory deficit and overall clinical severity in patients with neuropathic
      disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and
      12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical
      evaluation of basic auditory processing (intensity discrimination/temporal
      resolution) and binaural speech perception assessment using the Listening in
      Spatialized Noise test. Age, gender and hearing-level-matched controls were also
      tested. Speech perception in noise for individuals with auditory neuropathy was
      abnormal for each listening condition, but was particularly affected in
      circumstances where binaural processing might have improved perception through
      spatial segregation. Ability to use spatial cues was correlated with temporal
      resolution suggesting that the binaural-processing deficit was the result of
      disordered representation of timing cues in the left and right auditory nerves.
      Spatial processing was also related to overall disease severity (as measured by
      the Friedreich Ataxia Rating Scale and Charcot-Marie-Tooth Neuropathy Score)
      suggesting that the degree of neural dysfunction in the auditory system
      accurately reflects generalized neuropathic changes. Measures of binaural speech
      processing show promise for application in the neurology clinic. In individuals
      with auditory neuropathy due to both axonal and demyelinating mechanisms the
      assessment provides a measure of functional hearing ability, a biomarker capable
      of tracking the natural history of progressive disease and a potential means of
      evaluating the effectiveness of interventions.

PMID- 22982231
TI  - Novel small molecule activators of the Trk family of receptor tyrosine kinases.
AB  - The Tropomyosin-related kinase (Trk) receptors are a subset of the receptor
      tyrosine kinase family with an important functionality in the regulation of
      neurotrophic signaling in the peripheral and central nervous system. As the
      receptors are able to mediate neuronal survival by associating with their
      respective neurotrophin ligands, many studies have focused on the therapeutic
      potential of generating small-molecule mimetic compounds that elicit agonistic
      effects similar to those of the natural protein ligands. To this end, various
      structure-based studies have led to the generation of bivalent peptide-based
      agonists and antibodies that selectively initiate Trk receptor signaling;
      however, these compounds do not possess the ideal characteristics of a potential
      drug. Additionally, the reliance of structure-based data to generate the compound
      libraries, limits the potential identification of novel chemical structures with
      desirable activity. Therefore, subsequent investigations utilized a cell-based
      apoptotic screen to facilitate the analysis of large, diverse chemical libraries
      of small molecules and quickly identify compounds with Trk-dependent anti
      apoptotic activity. Herein, we describe the Trk agonists that have been
      identified by this screening methodology and summarize their in vitro and in vivo
      neurotrophic activity as well as their efficacy in various neurological disease
      models, implicating their future utility as therapeutic compounds. This article
      is part of a Special Issue entitled: Emerging recognition and activation
      mechanisms of receptor tyrosine kinases. 

PMID- 22982233
TI  - Nosema ceranae infection intensity highly correlates with temperature.
AB  - Nosema ceranae, a microsporidian entomopathogen, was first reported from honey
      bees, Apis mellifera, in 2005 in Taiwan (Huang et al., 2007) and has become a
      major concern in apiculture worldwide. In Taiwan, we found one infection peak for
      N. ceranae during the winter months, compared to two peaks in spring and fall
      reported in 1980 for Nosema apis. N. ceranae infection intensity in apiaries
      reached a high level earlier than N. apis, a possible factor in replacement. We
      found a significant negative correlation of N. ceranae pathogen load with
      temperature; the highest spore counts were recorded at an average temperature of
      approximately 15  degrees C and infection intensity equaled the annual average at
      23.8  degrees C. This model corresponds with published results but is most
      reliable for subtropical to tropical climates.

PMID- 22982234
TI  - Determination of the critical residues responsible for cardiac myosin binding
      protein C's interactions.
AB  - Despite early demonstrations of myosin binding protein C's (MyBP-C) interaction
      with actin, different investigators have reached different conclusions regarding
      the relevant and necessary domains mediating this binding. Establishing the
      detailed structure-function relationships is needed to fully understand cMyBP-C's
      ability to impact on myofilament contraction as mutations in different domains
      are causative for familial hypertrophic cardiomyopathy. We defined cMyBP-C's N
      terminal structural domains that are necessary or sufficient to mediate
      interactions with actin and/or the head region of the myosin heavy chain (S2
      MyHC). Using a combination of genetics and functional assays, we defined the
      actin binding site(s) present in cMyBP-C. We confirmed that cMyBP-C's C1 and m
      domains productively interact with actin, while S2-MyHC interactions are
      restricted to the m domain. Using residue-specific mutagenesis, we identified the
      critical actin binding residues and distinguished them from the residues that
      were critical for S2-MyHC binding. To validate the structural and functional
      significance of these residues, we silenced the endogenous cMyBP-C in neonatal
      rat cardiomyocytes (NRC) using cMyBP-C siRNA, and replaced the endogenous cMyBP-C
      with normal or actin binding-ablated cMyBP-C. Replacement with actin binding
      ablated cMyBP-C showed that the mutated protein did not incorporate into the
      sarcomere normally. Residues responsible for actin and S2-MyHC binding are
      partially present in overlapping domains but are unique. Expression of an actin
      binding-deficient cMyBP-C resulted in abnormal cytosolic distribution of the
      protein, indicating that interaction with actin is essential for the formation
      and/or maintenance of normal cMyBP-C sarcomeric distribution.

PMID- 22982235
TI  - Neuropeptide Y improves myocardial perfusion and function in a swine model of
      hypercholesterolemia and chronic myocardial ischemia.
AB  - Pharmacologically induced angiogenesis could be a promising option in clinical
      situations with diffuse inoperable coronary artery disease e.g. metabolic
      syndrome and diabetes mellitus. The failure of focused cytokine, stem cell and
      gene therapies to achieve both perfusion and functional improvement in clinical
      trials suggests a more centralized control mechanism. Neuropeptide-Y (NPY) is one
      such natural neurotransmitter that is known to exert a multifaceted role during
      neo-angiogenesis and can possibly act as the central control. To date, the
      ability to harness the 'master switch' nature of NPY in a specific experimental
      model of metabolic syndrome and chronic myocardial ischemia has not been
      conclusively demonstrated. We hypothesized that infiltration of NPY into an area
      of chronic ischemia in a metabolic syndrome swine model would induce angiogenesis
      and improve myocardial perfusion and function. An osmotic pump was inserted three
      weeks after surgical induction of focal myocardial ischemia. We delivered either
      NPY or placebo for five weeks, after which the myocardial tissue was harvested
      for analysis. Assessments of myocardial perfusion and function were performed at
      each stage of the experiment. Local infiltration of NPY significantly improved
      collateral vessel formation, blood flow and myocardial function. We believe
      activation of NPY receptors may be a potential target therapy for patients with
      diffuse coronary artery disease.

PMID- 22982236
TI  - Targeted imaging of activated caspase-3 in the central nervous system by a dual
      functional nano-device.
AB  - The activation of caspase-3 mediated neuron death is a common process in
      neurodegenerative diseases. Efficient activated caspase-3 imaging in brain would
      be helpful to monitor the potential lesion and intervene promptly. However, the
      blood-brain barrier (BBB) is the major obstacle that hinders the delivery of
      diagnostic agents into the brain. Herein, the fluorescence resonance energy
      transfer (FRET) was successfully applied to detect in vivo activated caspase-3 in
      apoptotic neuron with a brain-targeted nano-device, which was based on
      dendrigraft poly-L-lysines (DGLs) and linked with a brain-targeted peptide RVG29
      as well as the caspase-3 cleavable peptide linker (DEVD). This nano-device could
      detect the level of caspase-3 activation in accordance with the degree of
      apoptosis in rat brain; meanwhile normal rat showed no fluorescence signal. The
      location of fluorescence signal was confirmed to accumulate more in caspase-3
      activated neurons. Taken together, our nano-device would help to image activated
      caspase-3 in vivo and hold great promise in early diagnosis of neurodegenerative
      diseases.

PMID- 22982237
TI  - Vascular-targeted nanotherapy for obesity: unexpected passive targeting mechanism
      to obese fat for the enhancement of active drug delivery.
AB  - We previously reported that nanoparticles (NPs) modified with a prohibitin-homing
      peptide ligand via a short PEG(2kDa)-spacer could deliver its pay-load into the
      cytoplasm of endothelial cells in murine adipose tissue and escape from
      endosomes/lysosomes in vitro. We herein report, for the first time, on a dual
      targeting strategy for mediating the enhanced targeting activity of NPs to
      adipose endothelial cells in diet-induced obesity (DIO). The targeted
      accumulation of prohibitin-targeted nanoparticles (PTNP), modified with a peptide
      ligand via a long PEG-linker, was significantly increased in white fat vessels of
      normal healthy mice compared to the other non-PEGylated targeted NPs, whereas the
      undesired accumulation of PTNP in the liver was considerably reduced. These
      results demonstrate that the PEGylation of targeted NPs is a critical factor in
      maximizing the in vivo targeted delivery of NPs and can be attributed to a
      significant decrease in recognition by the reticuloendothelial system. After
      systemic administration to DIO mice, PTNP exclusively accumulated in both adipose
      vessels and angiogenic clusters of obese fat cells. Surprisingly, PEGylated NPs
      with no active targeting moieties also accumulated in these clusters,
      demonstrating that the nanoscaled carriers passively accumulate in clusters via a
      mechanism similar to that for the enhanced permeability and retention effect, as
      has been well established in tumor targeting. Therefore, the enhanced delivery of
      PTNP appears to be mediated by both passive accumulation to angiogenic regions
      and active recognition by endothelial cells. Thus, the systemic administration of
      a proapoptotic peptide with the delivery via PTNP significantly reduced the body
      weight of DIO mice, as evidenced by the targeted ablation of adipose endothelial
      cells. These findings are potentially useful in terms of the design and
      development of vascular-targeted nanotherapy in the effective control of obesity.

PMID- 22982238
TI  - Modeling studies with Helicobacter pylori octaprenyl pyrophosphate synthase
      reveal the enzymatic mechanism of trans-prenyltransferases.
AB  - Octaprenyl pyrophosphate synthase (OPPs), an enzyme belonging to the trans
      prenyltransferases family, is involved in the synthesis of C40 octaprenyl
      pyrophosphate (OPP) by reacting farnesyl pyrophosphate (FPP) with five
      isopentenyl pyrophosphates (IPP). It has been reported that OPPs is essential for
      bacteria's normal growth and is a potential target for novel antibacterial drug
      design. Here we report the crystal structure of OPPs from Helicobacter pylori,
      determined by MAD method at 2.8 A resolution and refined to 2.0 A resolution. The
      substrate IPP was docked into HpOPPs structure and residues involved in IPP
      recognition were identified. The other substrate FPP, the intermediate GGPP and a
      nitrogen-containing bisphosphonate drug were also modeled into the structure. The
      resulting model shed some lights on the enzymatic mechanism, including (1)
      residues Arg87, Lys36 and Arg39 are essential for IPP binding; (2) residues
      Lys162, Lys224 and Gln197 are involved in FPP binding; (3) the second DDXXD motif
      may involve in FPP binding by Mg(2+) mediated interactions; (4) Leu127 is
      probably involved in product chain length determination in HpOPPs and (5) the
      intermediate products such as GGPP need a rearrange to occupy the binding site of
      FPP and then IPP is reloaded. Our results also indicate that the nitrogen
      containing bisphosphonate drugs are potential inhibitors of FPPs and other trans
      prenyltransferases aiming at blocking the binding of FPP.

PMID- 22982240
TI  - Biophysical signals controlling cell fate decisions: how do stem cells really
      feel?
AB  - Self-renewal and differentiation are fundamental stem cell fate decisions, which
      are essential for normal tissue development, homeostasis, and repair.
      Extracellular signals, including mechanical and biophysical forces, play an
      important role in directing the behaviour of a variety of stem and progenitor
      cells, and recent studies have provided new insights into the molecular
      mechanisms of these responses. While integrin receptors transmit forces from the
      extracellular matrix to the cell, the actin cytoskeleton and Rho-GTPases, mediate
      downstream signal transduction. To affect stem cell fate, however, these
      signalling cascades must ultimately be transduced into specific transcription
      responses. Serum response factor (SRF) and yes-associated protein (YAP) are two
      examples of mechano-sensitive transcription factors, which have recently been
      implicated in epidermal and mesenchymal stem cell differentiation. Significant
      challenges for future studies will likely include measuring the relevant
      biophysical forces experienced by cells in vivo and translating the current
      knowledge into regenerative therapies.

PMID- 22982239
TI  - A relatively low level of ribosome depurination by mutant forms of ricin toxin A
      chain can trigger protein synthesis inhibition, cell signaling and apoptosis in
      mammalian cells.
AB  - The A chain of the plant toxin ricin (RTA) is an N-glycosidase that inhibits
      protein synthesis by removing a specific adenine from the 28S rRNA. RTA also
      induces ribotoxic stress, which activates stress-induced cell signaling cascades
      and apoptosis. However, the mechanistic relationship between depurination,
      protein synthesis inhibition and apoptosis remains an open question. We
      previously identified two RTA mutants that suggested partial independence of
      these processes in a yeast model. The goals of this study were to establish an
      endogenous RTA expression system in mammalian cells and utilize RTA mutants to
      examine the relationship between depurination, protein synthesis inhibition, cell
      signaling and apoptosis in mammalian cells. The non-transformed epithelial cell
      line MAC-T was transiently transfected with plasmid vectors encoding precursor
      (pre) or mature forms of wild-type (WT) RTA or mutants. PreRTA was glycosylated
      indicating that the native signal peptide targeted RTA to the ER in mammalian
      cells. Mature RTA was not glycosylated and thus served as a control to detect
      changes in catalytic activity. Both pre- and mature WT RTA induced ribosome
      depurination, protein synthesis inhibition, activation of cell signaling and
      apoptosis. Analysis of RTA mutants showed for the first time that depurination
      can be reduced by 40% in mammalian cells with minimal effects on inhibition of
      protein synthesis, activation of cell signaling and apoptosis. We further show
      that protein synthesis inhibition by RTA correlates more linearly with apoptosis
      than ribosome depurination.

PMID- 22982241
TI  - Expression of CD20 reveals a new store-operated calcium entry modulator in
      skeletal muscle.
AB  - Among the scarce available data about the biological role of the membrane protein
      CD20, there is some evidence that this protein functions as a store-operated
      Ca(2+) channel and/or regulates transmembrane Ca(2+) trafficking. Recent findings
      indicate that store-operated Ca(2+) entry (SOCE) plays a central role in skeletal
      muscle function and development, but there remain a number of unresolved issues
      relating to SOCE modulation in this tissue. Here we describe CD20 expression in
      skeletal muscle, verifying its membrane localization in myoblasts and adult
      muscle fibers. Additionally, we show that inhibition of CD20 through antibody
      binding or gene silencing resulted in specific impairment of SOCE in C2C12
      myoblasts. Our results provide novel insights into the CD20 expression pattern,
      and suggest that functional CD20 is required for SOCE to consistently occur in
      C2C12 myoblasts. These findings may contribute to future identification of
      mechanisms and molecules involved in the fine regulation of store-operated Ca(2+)
      entry in skeletal muscle.

PMID- 22982242
TI  - Selenoprotein W promotes cell cycle recovery from G2 arrest through the
      activation of CDC25B.
AB  - Selenoprotein W (SelW) contains a highly reactive selenocysteine (Sec; U) in the
      CXXU motif corresponding to the CXXC motif in thioredoxin (Trx) and thus it
      appears to be involved in regulating the cellular redox state. Recent reports on
      the interaction between SelW and 14-3-3 suggest that SelW may be redox
      dependently involved in the cell cycle. However, the precise function of SelW has
      not yet been elucidated. Here, we show that SelW is involved in the G2-M
      transition, especially in the recovery from G2 arrest after deoxyribonucleic acid
      (DNA) damage. Knockdown of SelW significantly accumulated phosphorylated cyclin
      dependent kinase (Cdk1), which eventually led to a delay in recovery from G2
      arrest. We also found that inactive Cdk1 is caused by the sustained inactivation
      of CDC25B, which removes the inhibitory phosphate from Cdk1. Our observation from
      this study reveals that SelW activated CDC25B by promoting the dissociation of 14
      3-3 from CDC25B through the reduction of the intramolecular disulfide bond during
      recovery. We suggest that SelW plays an important role in the recovery from G2
      arrest by determining the dissociation of 14-3-3 from CDC25B in a redox-dependent
      manner.

PMID- 22982243
TI  - OmpA can form folded and unfolded oligomers.
AB  - The monomeric outer membrane protein OmpA from Escherichia coli has long served
      as a model protein for studying the folding and membrane insertion of beta-barrel
      membrane proteins. Here we report that when OmpA is refolded in limiting amounts
      of surfactant (close to the cmc), it has a high propensity to form folded and
      unfolded oligomers. The oligomers exist both in a folded and (partially) unfolded
      form which both dissociate under denaturing conditions. Oligomerization does not
      require the involvement of the periplasmic domain and is not strongly affected by
      ionic strength. The folded dimers can be isolated and show native-like secondary
      structure; they are resistant to proteolytic attack and do not dissociate in high
      surfactant concentrations, indicating high kinetic stability once formed.
      Remarkably, OmpA also forms significant amounts of higher order structures when
      refolding in the presence of lipid vesicles. We suggest that oligomerization
      occurs by domain swapping favored by the high local concentration of OmpA
      molecules congregating on the same micelle or vesicle. In this model, the
      unfolded oligomer is stabilized by a small number of intermolecular beta-strand
      contacts and subsequently folds to a more stable state where these intermolecular
      contacts are consolidated in a native-like fashion by contacts between
      complementary beta-strands from different molecules. Our model is supported by
      the ability of complementary fragments to associate with each other in vitro.
      Oligomerization is probably avoided in the cell by the presence of cellular
      chaperones which maintain the protein in a monomeric state.

PMID- 22982244
TI  - How phosphorylation activates the protein phosphatase-1 * inhibitor-2 complex.
AB  - Phosphorylation regulates activity of many proteins; however, atomic level
      details are known for very few examples. Inhibitor-2 (I2) squelches the
      ubiquitous protein phosphatase-1 (PP1) enzyme activity by blocking access to the
      metal-containing active site. I2 Thr74 phosphorylation results in PP1 activation
      without I2 dissociation from the PP1-I2 complex. The dynamic disordered structure
      of the 73-residue segment of I2 containing Thr74, prevented visualization by X
      ray crystallography of PP1-I2. In this work, I generated structures of this
      segment using simulated annealing to NMR restraints, fused them to the
      crystallographic PP1-I2 coordinates, and used molecular dynamics to study the
      impact of Thr74 phosphorylation on structural alterations leading to PP1
      activation. Frequencies of I2 Tyr149 displacement from the PP1 active site,
      rotation of the phenolic Tyr149 side chain to prevent its reinsertion, and
      repositioning the I2 inhibitory helix to expose the PP1 active site to solvent
      and substrates significantly increased upon I2 Thr74 phosphorylation. After these
      steps, a second metal bound to produce PP1-Mn(2)-I2, which held the
      phosphorylated form of I2 to its active site less tightly than it held
      dephosphorylated I2. I2 Thr74 lies on the edge of variable dynamic communities of
      residues where it forms various allosteric pathways that induce motions at the
      PP1 active site 20A away. These molecular dynamics simulations show how an
      unstructured region of I2 can harness enhanced rapid movements around
      phosphorylated Thr74 to pry I2 residues away from the PP1 active site in early
      steps of PP1-I2 activation.

PMID- 22982245
TI  - Normal hematopoiesis and hematologic malignancies: role of canonical Wnt
      signaling pathway and stromal microenvironment.
AB  - Wnts are a family of evolutionary-conserved secreted signaling molecules
      critically involved in a variety of developmental processes and in cell fate
      determination. A growing body of evidence suggests that Wnt signaling plays a
      crucial role in the influence of bone marrow stromal microenvironment on the
      balance between hematopoietic stem cell self-renewal and differentiation.
      Emerging clinical and experimental evidence also indicates Wnt signaling
      involvement in the disruption of the latter balance in hematologic malignancies,
      where the stromal microenvironment favors the homing of cancer cells to the bone
      marrow, as well as leukemia stem cell development and chemoresistance. In the
      present review, we summarize and discuss the role of the canonical Wnt signaling
      pathway in normal hematopoiesis and hematologic malignancies, with regard to
      recent findings on the stromal microenvironment involvement in these process and
      diseases.

PMID- 22982246
TI  - Coronal craniosynostosis and radial ray hypoplasia: a third report of Twist
      mutation in a 33 weeks fetus with diaphragmatic hernia.
AB  - We describe a multiple malformation syndrome comprising coronal craniosynostosis,
      unilateral radial ray hypoplasia and diaphragmatic hernia in a 33w female fetus
      born to a 46 y-old male with an alleged personal and family history of Crouzon
      syndrome. By identifying an already described c.445C>T TWIST missense mutation,
      we were able to reassign the diagnosis of the family condition to Saethre-Chotzen
      syndrome. The present report illustrates clinical variability of a dominantly
      inherited TWIST mutation and provides a third example of Baller-Gerold/Saethre
      Chotzen overlapping phenotype. We also add diaphragmatic hernia in the spectrum
      of TWIST-related malformations, although we couldn't prove the co-occurrence is
      not coincidental.

PMID- 22982247
TI  - Prenatal diagnosis of the duplication 17p11.2 associated with Potocki-Lupski
      syndrome in a foetus presenting with mildly dysmorphic features.
AB  - Duplication 17p11.2 (Potocki-Lupski syndrome (PTLS) MIM# 610883) is a genomic
      disorder with an estimated incidence of 1 in 25,000 births. As for other genomic
      disorders this duplication is typically de novo and is not associated with
      advanced maternal age or advanced paternal age. Herein we describe a prenatal
      diagnosis of duplication 17p11.2. This diagnosis was not suspected as the
      prenatal ultrasound findings were non-specific; however, BACs-on-BeadsTM
      technology and array comparative genomic hybridization (aCGH) confirmed the
      common ~3.7 Mb duplication. Evaluation of the foetus following termination of
      pregnancy revealed mildly dysmorphic features as well as congenital anomalies not
      previously reported in PTLS, specifically left pulmonary isomerism, an abnormally
      positioned left coronary orifice and nodular cerebellar heterotopia. This report
      exemplifies the utility of prenatal testing using new genomic technologies even
      when there are no multiple anomalies on foetal ultrasound. This report also
      exemplifies the utility of foetal autopsy in the identification of "occult"
      congenital anomalies.

PMID- 22982248
TI  - NMDA receptor signaling mediates the expression of protein inhibitor of activated
      STAT1 (PIAS1) in rat hippocampus.
AB  - Protein inhibitor of activated STAT1 (PIAS1) was shown to play an important role
      in inflammation and innate immune response, but how PIAS1 is regulated is not
      known. We have recently demonstrated that PIAS1 enhances spatial learning and
      memory performance in rats. In this study, we examined the signaling pathway and
      neural mechanism that regulate PIAS1 expression in the brain by using
      pharmacological and molecular approaches. Our results revealed that pias1 gene
      expression is rapidly induced upon NMDA receptor activation in rat hippocampus,
      but this effect is blocked by transfection of sub-threshold concentrations of
      ERK1 siRNA/ERK2 siRNA or CREB siRNA. Pias1 gene expression is similarly induced
      by overexpression of the ERK1/ERK2 plasmids in rat hippocampus, and this effect
      is also blocked by sub-threshold concentration of CREB siRNA transfection. On the
      other hand, transfection of ERK1 siRNA/ERK2 siRNA or CREB siRNA at a higher
      concentration is sufficient to down-regulate PIAS1 expression. Inhibition of PI-3
      kinase signaling and CaMKII signaling, which both result in CREB inactivation,
      similarly decreases PIAS1 expression. But NMDA and MK-801 do not affect the
      expression of IL-6 and TNFalpha. NMDA also did not affect the expression of
      PIAS2, PIAS3 and PIAS4. Further, pias1 mRNA has a similar degradation rate to
      that of the zif268 gene. These results together suggest that pias1 may function
      as an immediate early gene in an activity-dependent manner and PIAS1 expression
      is regulated by the NMDA-MAPK/ERK-CREB signaling pathway implicated in neuronal
      plasticity.

PMID- 22982249
TI  - Evidence for a role of a dopamine/5-HT6 receptor interaction in cocaine
      reinforcement.
AB  - The putative 5-HT6 receptor agonist ST1936 has been shown to increase
      extracellular dopamine (DA) in the n.accumbens (NAc) shell and in the medial
      prefrontal cortex (PFCX). These observations suggest that 5-HT6 receptors
      modulate DA transmission in mesolimbic and mesocortical terminal DA areas. To
      investigate the behavioral counterpart of this interaction we studied in rats 1)
      the ability of ST1936 to maintain i.v. self-administration in fixed ratio (FR)
      and progressive ratio (PR) schedules of reinforcement; 2) the effect of 5-HT6
      receptor blockade on cocaine stimulated overflow of DA in dialysates from the
      PFCX and from the NAc shell and on cocaine i.v. self-administration. ST1936 was
      i.v. self-administered at unitary doses of 0.5-1 mg/kg on an FR1 and PR schedule
      of reinforcement, with breaking point of about 4. Pretreatment with the 5-HT6
      antagonist SB271046 reduced by about 80% responding for ST1936. SB271046 also
      reduced cocaine-induced increase of dialysate DA in the NAc shell but not in the
      PFCX and impaired i.v. cocaine self-administration. These observations indicate
      that ST1936 behaves as a weak reinforcer and suggest that 5-HT6 receptors play a
      role in cocaine reinforcement via their facilitatory interaction with DA
      projections to the NAc shell. This novel 5-HT/DA interaction might provide the
      basis for a new pharmacotherapeutic strategy of cocaine addiction.

PMID- 22982250
TI  - The influence of cognitive processes on rural landholder responses to climate
      change.
AB  - Global climate change modelling has identified south-east Australia as a 'hot
      spot' for more frequent climatic extremes. Rural landholders may be vulnerable to
      the risks climate change presents. Australia's rural landholders are considered
      highly adaptable, with a history of responding to climatic uncertainty and
      variability. Yet it is possible that some of their adaptations will not be
      effective in reducing vulnerability, and may have downstream impacts. Rural
      landholder decision making is complex, and this is one of a limited number of
      papers examining rural landholder responses to climate change and the factors
      influencing their decisions. Data were gathered using semi-structured interviews
      and a mail survey of rural landholders in two districts. Established socio
      psychological scales were employed to measure beliefs, values and attitudes that
      are expected to shape landholder behaviour. Most of the rural landholders
      surveyed were not climate change 'deniers' with 70% agreeing that the climate is
      changing and that human activity is a major influence. Climate change was
      nominated as an influence on six adaptive behaviours by 50% or more of survey
      respondents. However, there were no significant relationships between belief in
      climate change and adaptive actions. Personal values and worldviews were found to
      be the most frequent factors linked to adaptive behaviour. These findings
      illustrate the complex nature of rural landholder decision making: suggesting
      that many rural landholders do not need convincing of the existence of climate
      change; and that efforts to motivate rural landholders to respond to climate
      change risks should be based on sound knowledge of their values and worldviews.

PMID- 22982253
TI  - The myosin interacting-heads motif is present in the relaxed thick filament of
      the striated muscle of scorpion.
AB  - Electron microscopy (EM) studies of 2D crystals of smooth muscle myosin molecules
      have shown that in the inactive state the two heads of a myosin molecule interact
      asymmetrically forming a myosin interacting-heads motif. This suggested that
      inactivation of the two heads occurs by blocking of the actin-binding site of one
      (free head) and the ATP hydrolysis site of the other (blocked head). This motif
      has been found by EM of isolated negatively stained myosin molecules of
      unregulated (vertebrate skeletal and cardiac muscle) and regulated (invertebrate
      striated and vertebrate smooth muscle) myosins, and nonmuscle myosin. The same
      motif has also been found in 3D-reconstructions of frozen-hydrated (tarantula,
      Limulus, scallop) and negatively stained (scallop, vertebrate cardiac) isolated
      thick filaments. We are carrying out studies of isolated thick filaments from
      other species to assess how general this myosin interacting-heads motif is. Here,
      using EM, we have visualized isolated, negatively stained thick filaments from
      scorpion striated muscle. We modified the iterative helical real space
      reconstruction (IHRSR) method to include filament tilt, and band-pass filtered
      the aligned segments before averaging, achieving a 3.3 nm resolution 3D
      reconstruction. This reconstruction revealed the presence of the myosin
      interacting-heads motif (adding to evidence that is widely spread), together with
      12 subfilaments in the filament backbone. This demonstrates that conventional
      negative staining and imaging can be used to detect the presence of the myosin
      interacting-heads motif in helically ordered thick filaments from different
      species and muscle types, thus avoiding the use of less accessible cryo-EM and
      low electron-dose procedures.

PMID- 22982252
TI  - Stabilization of sphingomyelin interactions by interfacial hydroxyls - a study of
      phytosphingomyelin properties.
AB  - D-ribo-phytosphingosines are biologically significant long-chain bases present in
      various sphingolipids from yeasts, fungi, plants and mammals. In this study we
      prepared phytopalmitoylsphingomyelin (phytoPSM) analogs based on the D-ribo
      phytosphingosine base. The N-linked acyl chains were either 16:0, 2OH(R)16:0
      (natural isomer), or 2OH(S)16:0. The gel-phase of phytoPSM was more stable than
      that of PSM (T(m) 48.6 degrees C and 41.0 degrees C, respectively). The gel
      liquid crystalline phase transition enthalpies were 9.1+/-0.4 and 6.1+/
      0.3kcal/mol for phytoPSM and PSM, respectively. An N-linked 2OH(R)16:0 in
      phytoPSM destabilized the gel phase relative to phytoPSM (by ~+6 degrees C, based
      on DPH anisotropy measurements), whereas 2OH(S)16:0 in phytoPSM stabilized it (by
      ~-6 degrees C). All phytoPSM analogs formed sterol-enriched ordered domains in a
      fluid ternary bilayer, and those containing phytoPSM or 2OH(S)phytoPSM were more
      thermostable than the domains containing 2OH(R)phytoPSM or PSM. The affinity of
      cholestatrienol for POPC bilayers containing 20mol% phytoPSM was higher than for
      comparable bilayers with an equal amount of PSM. The 2-hydroxylated acyl chains
      in phytoPSM did not markedly alter sterol affinity. We conclude that phytoPSM is
      a more ordered sphingolipid than PSM, and is fully capable of interacting with
      cholesterol.

PMID- 22982251
TI  - Protection against cardiac injury by small Ca(2+)-sensitive K(+) channels
      identified in guinea pig cardiac inner mitochondrial membrane.
AB  - We tested if small conductance, Ca(2+)-sensitive K(+) channels (SK(Ca))
      precondition hearts against ischemia reperfusion (IR) injury by improving
      mitochondrial (m) bioenergetics, if O(2)-derived free radicals are required to
      initiate protection via SK(Ca) channels, and, importantly, if SK(Ca) channels are
      present in cardiac cell inner mitochondrial membrane (IMM). NADH and FAD,
      superoxide (O(2)(-)), and m[Ca(2+)] were measured in guinea pig isolated hearts
      by fluorescence spectrophotometry. SK(Ca) and IK(Ca) channel opener DCEBIO (DCEB)
      was given for 10 min and ended 20 min before IR. Either TBAP, a dismutator of
      O(2)()(-), NS8593, an antagonist of SK(Ca) isoforms, or other K(Ca) and K(ATP)
      channel antagonists, were given before DCEB and before ischemia. DCEB treatment
      resulted in a 2-fold increase in LV pressure on reperfusion and a 2.5 fold
      decrease in infarct size vs. non-treated hearts associated with reduced O(2)(-)
      and m[Ca(2+)], and more normalized NADH and FAD during IR. Only NS8593 and TBAP
      antagonized protection by DCEB. Localization of SK(Ca) channels to mitochondria
      and IMM was evidenced by a) identification of purified mSK(Ca) protein by Western
      blotting, immuno-histochemical staining, confocal microscopy, and immuno-gold
      electron microscopy, b) 2-D gel electrophoresis and mass spectroscopy of IMM
      protein, c) [Ca(2+)]-dependence of mSK(Ca) channels in planar lipid bilayers, and
      d) matrix K(+) influx induced by DCEB and blocked by SK(Ca) antagonist UCL1684.
      This study shows that 1) SK(Ca) channels are located and functional in IMM, 2)
      mSK(Ca) channel opening by DCEB leads to protection that is O(2)(-) dependent,
      and 3) protection by DCEB is evident beginning during ischemia.

PMID- 22982254
TI  - Selective inhibition of monoamine oxidase A or B reduces striatal oxidative
      stress in rats with partial depletion of the nigro-striatal dopaminergic pathway.
AB  - Partial lesion (50%) of the nigro-striatal dopaminergic pathway induces
      compensatory increase in dopamine release from the remaining neurons and
      increased extracellular oxidative stress (OS(-ec)) in the striatum. The present
      study was designed to explore the role of monoamine oxidase types A and B (MAO-A,
      MAO-B) in producing this increased oxidative stress. Lesion of the dopaminergic
      pathways in the CNS was produced in rats by intra-cerebroventricular injection of
      6-hydroxydopamine (6-OHDA; 250 MUg) and striatal microdialysis was carried out 5
      weeks later. Striatal OS(ec) was determined by measurement of oxidized
      derivatives of the marker molecule N-linoleyl-tyrosine. Striatal tissue MAO-A
      activity was unchanged by 6-OHDA lesion but MAO-B activity was increased by 16%,
      together with a 45% increase in glial cell content. The selective MAO-B inhibitor
      rasagiline (0.05 mg/kg s.c. daily for 14 days) did not affect microdialysate
      dopamine concentration [DA(ec)] in sham-operated rats, but decreased OS(ec) by
      30%. In lesioned rats, rasagiline decreased [DA(ec)] by 42% with a 49% reduction
      in OS(ec). The decrease in [DA(ec)] was reversed by the dopamine D2 receptor
      antagonist sulpiride (10 mg/kg s.c.). The selective MAO-A inhibitor clorgyline
      (0.2 mg/kg s.c. daily for 14 days) increased striatal [DA(ec)] by 72% in sham
      operated rats with no change in OS(ec). In lesioned rats clorgyline increased
      [DA(ec)] by 66% and decreased OS(ec) by 44%. Rasagiline and clorgyline were
      effective to a similar extent in reduction of tissue levels of 7-ketocholesterol
      and the ratio GSSG/GSH, indicative of reduced intracellular oxidative stress
      level. This data implies that gliosis in our 6-OHDA animals together with
      inhibition of glial cell MAO-B by rasagiline causes an increase in local levels
      of dopamine at the presynaptic receptors, and a reduction in dopamine release
      (and in [DA(ec)]) by presynaptic inhibition. Moreover, inhibition of MAO-A or MAO
      B reduces the enhanced level of oxidative stress in the lesioned striatum, and
      while both clorgyline and rasagiline reduced DA oxidative metabolism, rasagiline
      possesses an additional antioxidant property, not only that resulting from MAO
      inhibition.

PMID- 22982255
TI  - Changes in ultra-structures and electrophysiological properties in HVC of
      untutored and deafened Bengalese finches relation to normally reared birds:
      implications for song learning.
AB  - Songbirds are increasingly used as an experimentally tractable system to study
      the neurobiological underpinnings of vocal learning. To gain additional insights
      into how birdsongs are learned, we compared the size of HVC, the high vocal
      center for song production, and its ultrastructural or electrophysiological
      properties between the normally reared Bengalese finches, and the untutored or
      deafened ones before the onset of sensory learning (around post-hatching day 20).
      Our results showed that HVC had more synapses and concave synaptic curvature, but
      fewer perforated synapse, in the untutored or deafened birds in comparison with
      those in the normally reared birds. Although there was no significant difference
      of the ratio of straight or compound synapses, there was an increasing tendency
      for the untutored and deafened birds to possess more straight and compound
      synapses. These data revealed that synapses in the isolated or deafened birds had
      lower synapse activity in relation to those with normal hearing. This was
      confirmed by our electrophysiological results to show significant decreases in
      the firing rates of spike or burst in the isolated or deafened birds in the three
      types of HVC neurons i.e., putative X-projecting neurons, RA-projecting neurons
      and interneurons. In addition, low firing frequency (<10Hz) occurred much more in
      the above three types of HVC neurons in the tutored or deafened birds than in the
      normally reared birds. These data suggest that all the three putative types of
      neurons in HVC might be involved in the activity of the production of adult
      normal songs.

PMID- 22982256
TI  - Wireless transmission of ultrasonic waveforms for monitoring drug tablet
      properties and defects.
AB  - The geometric and mechanical properties of pharmaceutical materials are crucial
      to their structural, functional and therapeutic effectiveness. The implementation
      of automated and convenient quality monitoring procedures is an attempt to
      balance control of quality against the level of testing; within acceptable levels
      of probability and costs. The capability of rapid/extensive inspections with
      minimal time and manufacturing interruption make non-contact quality monitoring
      systems a desirable approach to optimize this balance. In the current study, a
      wireless transceiver proof of concept system developed for the real-time quality
      monitoring of tablets during compaction is presented and demonstrated. The
      effectiveness of ultrasonic wave transmission through the punch-tablet interface
      is the boundary condition that dictates the viability of the acoustic in-die
      compaction monitoring approach. These measurements in the current experimental
      set-up can be used in determining various mechanical and geometric properties of
      a compact, such as the tablet thickness, mass density, elasticity and/or
      integrity of the tablet core, and bonding quality between layers depending on the
      given parameters, as it is compacted. In the current study, it is demonstrated
      that the reflection of an ultrasonic pulse generated by a transducer embedded in
      an upper punch from the lower punch-tablet interface can be acquired by the same
      transducer in the upper punch and the analog waveform can be transmitted to a
      computer by means of wireless communications for further signal processing and
      property extraction. The evolution of apparent Young's moduli of a powder bed
      during a full-compaction cycle is derived from the ultrasonic time of flight of
      an acoustic waveform acquired during compaction in-die.

PMID- 22982257
TI  - Design flexibility influencing the in vitro behavior of cationic SLN as a
      nonviral gene vector.
AB  - Several advanced in vitro and in vivo studies have proved the broad potential of
      cationic solid lipid nanoparticles (SLN) as nonviral vectors. However, a few data
      are available about the correlation between lipid component of the SLN structure
      and in vitro performance in terms of cell tolerance and transfection efficiency
      on different cell lines. In this paper SLN were prepared using stearic acid as
      main lipid component, stearylamine as cationic agent and protamine as
      transfection promoter and adding phosphatidylcholine (PC), cholesterol (Chol) or
      both to obtain three different multicomponent SLN (SLN-PC, SLN-Chol and SLN-PC
      Chol, respectively). Cytotoxicity and transfection efficiency of the obtained
      SLN:pDNA complexes were evaluated on three different immortalized cell lines: COS
      I (African green monkey kidney cell line), HepG2 (human hepatocellular liver
      carcinoma cell line) and Na1300 (murine neuroblastoma cell line). Samples were
      characterized for the exact quantitative composition, particle size, morphology,
      zeta potential and pDNA binding ability. All the three SLN samples were about 250
      300 nm in size with a positive zeta potential, whereas SLN:pDNA complexes were
      about 300-400 nm in size with a less positive zeta potential, depending on the
      SLN composition. Concerning the cell tolerance, the three samples showed a level
      of cytotoxicity lower than that of the positive control polyethylenimine (PEI),
      regardless of the cell lines. The best transfection performance was observed for
      SLN-PC-Chol on COS-I cells while a transfection level lower than PEI was observed
      on HepG2 cells, regardless the SLN composition. On Na1300 cells, SLN-Chol showed
      a double efficiency with respect to PEI. Comparing these results to those
      obtained with the same kind of SLN without PC and/or Chol, it is possible to
      conclude that the addition of Chol and/or PC to the composition of cationic SLN
      modify the cell tolerance and the transfection efficiency of the gene vector in a
      manner strictly dependent on the cell type and the internalization pathways.

PMID- 22982258
TI  - Quaternized chitosan-organic rectorite intercalated composites based
      nanoparticles for protein controlled release.
AB  - Organic rectorite (OREC) was added in the quaternized chitosan (QC)/alginate
      (ALG) nanoparticles using an ionic gelation method to fabricate a controllable
      release system for proteins for the first time. The morphology of nanoparticles,
      the intercalated structure of OREC, bovine serum albumin encapsulation efficiency
      and in vitro release properties were investigated. Fourier transform infrared
      spectra, energy dispersive X-ray, X-ray photoelectron spectroscopy, small angle X
      ray diffraction and size distribution analysis were performed to characterize the
      composite nanoparticles. With the addition of OREC, the encapsulation efficiency
      and the loading capacity of nanoparticles had increased from 21.2% to 44.9% and
      from 13.7% to 25.0%, respectively. In addition, the rapid initial release was
      inhibited successfully from 20.15% to 11.07% in stimulated gastric fluid and from
      14.69% to 4.52% in stimulated intestinal fluid. The results verified that the
      addition of OREC could make these nanoparticles effective carriers to encapsulate
      drug and slow the drug controlled release of nanoparticles.

PMID- 22982259
TI  - Rapid detection of sequence variation in Clostridium difficile genes using LATE
      PCR with multiple mismatch-tolerant hybridization probes.
AB  - A novel molecular assay for Clostridium difficile was developed using Linear
      After-The-Exponential polymerase chain reaction (LATE-PCR). Single-stranded DNA
      products generated by LATE-PCR were detected and distinguished by hybridization
      to fluorescent mismatch-tolerant probes, as the temperature was lowered after
      amplification in 5( degrees )C intervals between 65 degrees C and 25 degrees C.
      Single-tube multiplex reactions for tcdA, tcdB, tcdC, and cdtB (binary toxin)
      sequences were initially optimized using synthetic targets and were subsequently
      done using genomic DNA; each target was detected and characterized by
      hybridization to one or more probes of a different fluorescent color. In the case
      of tcdC, three probes, each labeled with a Quasar fluorophore, hybridize to
      different locations with known mutations, including the deletion at nucleotide
      117 in ribotype 027 strains and the premature stop codon mutation at nucleotide
      184 in ribotype 078 strains, each of which is associated with hypervirulent
      infections. These and other tcdC mutations were distinguished from the reference
      sequence, as well as from each other by changes in the fluorescent contour
      generated from the combined Quasar-labeled probes. Specific variations in tcdA
      and tcdB were also identified in the multiplex assay, including those that
      identified strains lacking toxin A production. This single closed-tube assay
      generates substantially more information about virulent C. difficile than
      currently available commercial assays and could be further expanded to provide
      strain typing.

PMID- 22982260
TI  - Disruption to the development of maternal responsiveness? The impact of prenatal
      depression on mother-infant interactions.
AB  - Both prenatal and postnatal maternal depression are independently associated with
      an increased risk of adverse infant development. The impact of postnatal
      depression on infants may be mediated through the effect of depression in
      reducing maternal responsiveness. However, the mechanisms underlying the effect
      of prenatal depression are unclear. Using longitudinal data from over 900 mother
      infant pairs in a UK birth cohort (ALSPAC), we found that women with high
      depressive symptom scores during mid pregnancy, but NOT when their infants were 8
      months, had a 30% increased risk of low maternal responsiveness when the infant
      was 12 months compared to women with consistently low depression. This may
      provide a mechanism to explain the independent association between prenatal
      depression and poorer infant development.

PMID- 22982261
TI  - Sticking out and fitting in: culture-specific predictors of 3-year-olds'
      autobiographical memories during joint reminiscing.
AB  - The present study investigates the relationship between mother-child interaction
      styles with 19 months and children's autobiographical memory with 3 years of age
      in two cultural contexts: New Delhi, India (n = 25) and Berlin, Germany (n = 33).
      Results demonstrate similarities as well as culture specificities. In both
      contexts, maternal elaborations during reminiscing were related to children's
      memory contributions. Over time, maternal support for toddlers' self-expression
      during free play at 19 months predicted their children's memory elaborations at 3
      years in the Berlin context. In the Delhi context, toddlers' willingness to carry
      out their mothers' requests at 19 months predicted their memory elaborations at 3
      years. These results suggest different motivational bases underlying children's
      autobiographical memory contributions during mother-child reminiscing related to
      different cultural orientations.

PMID- 22982262
TI  - Attention engagement in early infancy.
AB  - We report a longitudinal study investigating developmental changes in the
      structure of attention engagement during early infancy. Forty-three infants were
      observed monthly from 2 to 4 months. Attention engagement was assessed from play
      interactions with parents, using a coding system developed by Bakeman and Adamson
      (1984). The results indicated a developmental transition in attention engagement
      at 3 months: after this age infants engaged for longer periods and in a wider
      variety of states. Most infants displayed person engagement at 2 months, passive
      joint engagement at 3 months, and object engagement at 4 months. To address
      whether emerging abilities of attention engagement allow infants to follow the
      attention of social partners, we compared attention engagement to performance on
      an experimental measure of attention control (reported by Perra & Gattis, 2010).
      Analyses revealed a positive relation between passive joint engagement and
      checking back, suggesting that changes in passive joint engagement reflect the
      development in attention control.

PMID- 22982263
TI  - Perseveration in congenitally blind children: effects of luminous and acoustic
      targets on a modified A-not-B task.
AB  - The purpose of this study was to determine whether or not blind children
      perseverate during a modified Piagetian A-not-B reaching task, with conditions
      that employ luminous AB targets and acoustic AB targets. Ten congenitally blind
      children, ages 1-4 years, with residual vision for light, took part in this
      study. Behavioral and kinematic data were computed for participants' reaches,
      performed in six A trials and in two B trials, in both stimulus conditions. All
      of the children perseverated in the luminous condition, and none of them
      perseverated in the condition using acoustic targets. The children tilted their
      heads in the direction of the target as they reached towards it. However, this
      coupling action (head-reaching) occurred predominantly in the A trials in the
      acoustic condition. In the luminous condition, in contrast to the acoustic
      condition, the children took longer times to initiate the reaching movement.
      Also, in the luminous condition, the children explored the target surroundings,
      unlike the acoustic condition, in which they reached straight ahead. For these
      blind children, sound was more relevant to reaching than was the luminous
      stimulus. The luminous input caused perseveration in congenitally blind children
      in a similar way that has been reported in the literature for typically
      developing, sighted infants, ages 8-12 months, performing A-not-B tasks with
      visual inputs.

PMID- 22982264
TI  - Maternal depression and infant birth measures relate to how neonates respond to
      music.
AB  - Two-week-old full-term newborns (26 born to depressed mothers and 26 born to non
      depressed mothers) were videotaped for three 2-min intervals during: (1) a
      baseline silent period, (2) the playing of a musical lullaby and, (3) the lullaby
      with vocals added. More maternal depression symptoms were associated with more
      obstetric complications and newborns spending less time awake during the two
      music intervals. When the lullaby was played, infants born to mothers with more
      obstetric complications cried more and made more facial expressions. Infants who
      made more facial expressions at baseline spent more time awake during the musical
      lullaby with vocals but showed more distress, whereas fewer facial expressions
      indicated greater attention. Greater birthweight was related to sleeping longer
      during baseline, but spending more time awake and making fewer facial expressions
      during the musical lullaby without voice. The findings are discussed in terms of
      potential factors that may relate to infant music preferences in the very early
      weeks of human development.

PMID- 22982265
TI  - Locus of control and prenatal depression.
AB  - Prenatal depression is a significant predictor of postpartum depression and is
      detrimental to fetal development. Locus of control was examined in this study as
      a potential predictor of prenatal depression. One hundred and thirty-three rural
      pregnant women recruited from obstetricians' offices completed the Levenson Scale
      on Locus of Control and the Edinburgh Postnatal Depression Scale. Multiple
      regression analysis indicated that after controlling for previous or current
      mental health problems, the External Locus of Control-Chance Scale accounted for
      17% of the variance in depression scores.

PMID- 22982266
TI  - Mother-infant synchrony during infant feeding.
AB  - PURPOSE: The purpose of this study was to test a coding system, the Maternal
      Infant Synchrony Scale (MISS), for assessing synchrony of feeding interaction
      between a mother and her preterm infant. The secondary aim was to describe mother
      and preterm infant synchrony during feeding and the change over time. METHODS: A
      descriptive, longitudinal design using data collected during an earlier study was
      employed, using a sample dataset from 10 mother-infant dyads that completed three
      data collection points. The Noldus Observer XT 8.0 (Noldus Information Technology
      b.v., 2006) was used for data review and coding. The MISS was created from pilot
      data and definitions further refined. The frequency of occurrence for select
      behaviors and the percentage of time behaviors occurred during the feeding and
      the changes in behaviors over the three observations periods were calculated.
      RESULTS: The synchrony tool developed in this study demonstrates that changes
      occur in mother and infant behavior over time. Mothers were attentive and focused
      during feedings and monitored their infants' sucking intently but there was
      little interaction between the dyad. Infant attempts at interaction were greater
      than the mother attempts to engage her infant. The influence of infant maturation
      on feeding behaviors was evident across observations. CONCLUSION: This study
      revealed behaviors that are descriptive of the interaction and can be used to
      develop interventions that would support the developing relationship. Use of the
      MISS with a larger sample size and a cohort of healthy, term newborns is needed
      to establish the MISS as a valid and reliable measure of synchrony.

PMID- 22982267
TI  - Prematurity and parental self-efficacy: the Preterm Parenting & Self-Efficacy
      Checklist.
AB  - There is a lack of research investigating parental self-efficacy in parents of
      infants born preterm as well as a paucity of parental self-efficacy measures that
      are domain-specific and theoretically grounded. This study aimed to compare
      parental self-efficacy in parents of infants born term, preterm and very preterm
      as well as to test whether parental self-efficacy mediates the relationship
      between psychological symptoms and parental competence. In order to achieve this,
      a new measure of parental self-efficacy and parental competence relevant for the
      preterm population and consistent with Bandura's (1977, 1986, 1989)
      conceptualisation of self-efficacy was developed. Participants included 155
      parents, 83 of whom were parents of very preterm (GA<32 weeks), 40 parents of
      preterm (GA<37 weeks) and 32 parents of term born infants. Parents completed the
      Preterm Parenting & Self-Efficacy Checklist (the new measure), Family Demographic
      Questionnaire, Depression Anxiety Stress Scale and Self-Efficacy Questionnaire.
      This initial study indicates that the Preterm Parenting & Self-Efficacy Checklist
      has adequate content validity, construct validity, internal consistency and split
      half reliability. Contrary to expectations, parents of very preterm infants did
      not report significantly lower overall levels of parental self-efficacy or
      significantly higher levels of psychological symptoms compared to parents of
      preterm and term infants. Parental self-efficacy about parenting tasks mediated
      the relationship between psychological symptoms and self perceived parental
      competence as predicted. Clinical implications of the results and suggestions for
      future research are discussed.

PMID- 22982268
TI  - Dynamics of infant habituation: infants' discrimination of musical excerpts.
AB  - Schoner and Thelen (2006) summarized the results of many habituation studies as a
      set of generalizations about the emergence of novelty preferences in infancy. One
      is that novelty preferences emerge after fewer trials for older than for younger
      infants. Yet in habituation studies using an infant-controlled procedure, the
      standard criterion of habituation is a 50% decrement in looking regardless of he
      ages of the participants. If younger infants require more looking to habituate
      than do older infants, it might follow that novelty preferences will emerge for
      younger infants when a more stringent criterion is imposed, e.g., a 70% decrement
      in looking. Our earlier investigation of infants' discrimination of musical
      excerpts provides a basis and an opportunity for assessing this idea. Flom et al.
      (2008) found that 9-month-olds, but not younger infants, unambiguously
      discriminate "happy" and "sad" musical excerpts. The purpose of the current study
      was to examine younger infants' discrimination of happy and sad musical excerpts
      using a more stringent, 70% habituation criterion. In Experiment 1, 5- and 7
      month olds were habituated to three musical excerpts rated as happy or sad.
      Following habituation infants were presented with two musical excerpts from the
      other affect group. Infants at both ages showed significant discrimination. In
      Experiment 2, 5- and 7-month-olds were presented with two new excerpts from the
      same affective group as the habituation excerpts. The infants did not
      discriminate these novel, yet affectively similar excerpts. In Experiment 3, 5-
      and 7-month-olds discriminated individual happy and sad excerpts. These results
      replicate those for the older, 9-month-olds in the previous investigation. The
      results are important as they demonstrate that whether infants show
      discrimination using an infant-controlled procedure is affected by the
      researchers' chosen criterion of habituation.

PMID- 22982269
TI  - Infants' integration of featural and numerical information.
AB  - The current study examined the integration of non-numerical (featural) and
      numerical information in 9-, 11-, and 13-month-old infants' performance on a
      number discrimination task. Infants were habituated to pictures of objects (e.g.,
      bowl, shoe) either in groups of two or three. In the test phase, infants saw both
      new and old objects in both groups of two and three. Nine-month-old infants
      discriminated number independent of the familiarity of the object, 11-month-old
      infants discriminated between familiar and novel objects (but not the number of
      objects), and 13-month-old infants discriminated between the familiar and novel
      objects only in the context of a familiar number of objects. These data suggest
      that early number representations are dissociated from featural information, and
      that the integration of these stimulus properties is a developmental process that
      occurs across the first year.

PMID- 22982270
TI  - Infant visual attention and step responsiveness to optic flow during treadmill
      stepping.
AB  - This study examined infant treadmill stepping in two groups of pre-locomotor
      infants in response to terrestrial optic flow. The optic flow was provided via
      the treadmill belt for flow translation that was directionally consistent with
      the forward stepping of the infants. Twelve 2-5-month-old and twelve 7-10-month
      old infants participated. Visual attention (duration and direction) and step
      responsiveness (frequency and step types) were coded from digital video, and
      visuomotor coupling was examined by temporally juxtaposing the visual attention
      and step data. Longer durations of visual attention to the patterned belt with
      increased step frequencies during periods of visual attention were observed,
      suggesting that the visuotactile calibration afforded by the patterned treadmill
      belt, increased visuomotor coupling and enhanced the frequency and complexity of
      stepping in prelocomotor infants. The findings are discussed with regard to
      sensorimotor experiences that enhance treadmill stepping in infants and that may
      have application to clinical populations.

PMID- 22982271
TI  - Child and mother mental-state talk in shared pretense as predictors of children's
      social symbolic play abilities at age 3.
AB  - This study investigated relations between mother and child (N=49) mental-state
      talk during shared pretense and children's social symbolic play at age 3. Social
      symbolic play was not related to mothers' mental-state talk. In contrast,
      children's own use of desire-state talk in shared pretense was a better predictor
      of social symbolic play than their general use of mental-state talk, even after
      accounting for general verbal ability as well as mothers' use of desires terms.
      CONCLUSION: These results highlight for the first time a link between children's
      references to desires and their performance on social symbolic play at age 3
      years - a social cognitive ability thought to precede theory of mind.

PMID- 22982272
TI  - Are higher-frequency sounds brighter in color and smaller in size? Auditory
      visual correspondences in 10-month-old infants.
AB  - Previous research has shown that not only adults but also two-and-a-half-year-old
      children associate higher-frequency sounds with smaller objects and with objects
      of brighter colors, suggesting that these intersensory correspondences are based
      on neural connections present very early in life. The present research examined
      whether 10-month olds are sensitive to these intersensory correspondences using a
      violation-of-expectation procedure. The results of Experiment 1 indicated that 10
      month-olds associate a higher-frequency tone with an object of a brighter color
      and a lower-frequency tone with an object of a darker color. However, Experiment
      2 found that 10-month olds did not always associate a higher-frequency tone with
      a smaller object and a lower-frequency tone with a larger object. The results
      suggest that infants have an initial bias to associate pitch with brightness,
      whereas pitch-size correspondences may be learned after birth by observing
      statistical co-occurrence patterns in the real world.

PMID- 22982273
TI  - Attainment of sitting and walking predicts development of productive vocabulary
      between ages 16 and 28 months.
AB  - Productive vocabulary was measured every four months in 16- to 28-months-olds.
      Attainment of motor-milestones was also measured. An earlier age of sitting and
      walking predicted a higher intercept and a larger slope (growth) of productive
      vocabulary respectively, suggesting that attainment of walking propels linguistic
      development.

PMID- 22982274
TI  - Effects of familiarity and attentiveness of partner on 6-month-old infants'
      social engagement.
AB  - This study presents an ecological experiment investigating 6-month-olds' social
      engagement. Results show that infants look and smile more at a socially attending
      distant partner than at an inattentive partner and that their looking and smiling
      behavior is different when the inattentive partner is their mother.

PMID- 22982275
TI  - Is early manual preference in infants defined by intermanual performance
      asymmetry in reaching?
AB  - In the present study we evaluated the relationship between manual preference and
      intermanual performance asymmetry in reaching of 5-month-old infants. Manual
      preference was assessed through frequency of reaches toward toys presented at
      midline, left or right in egocentric coordinates. Intermanual performance
      asymmetry was evaluated through kinematic analysis. Results showed that
      performance was predominantly symmetric between hands. Lateral toy positions
      induced predominance of ipsilateral reaching, while the midline position led to
      equivalent distribution between right and left handed reaches. No significant
      correlation between manual preference and intermanual performance asymmetry was
      observed. These results converge against the notion that manual preference
      derives from a genetically determined advantage of movement control favoring the
      right hand.

PMID- 22982276
TI  - Discrimination and ordinal judgments of temporal durations at 3 months.
AB  - This study presents the first evidence that 3-month-old infants success in a
      timing matching task and in an ordinal timing task, when numerical information is
      controlled. Three-month-old infants discriminated brief temporal durations that
      differed by a 1:3 ratio, relying solely on temporal information. Moreover, at 3
      months of age infants were able to discriminate between monotonic and non
      monotonic time-based series, when numerical and temporal information were
      inconsistent. These findings strengthen the hypothesis that a magnitude
      representational system for temporal quantities is operating very early in the
      ontogenetic development.

PMID- 22982278
TI  - Twelve-month-olds' vocal production during pointing in naturalistic interactions:
      sensitivity to parents' attention and responses.

PMID- 22982277
TI  - The missing link: mothers' neural response to infant cry related to infant
      attachment behaviors.
AB  - This study addresses a gap in the attachment literature by investigating maternal
      neural response to cry related to infant attachment classifications and
      behaviors. Twenty-two primiparous mothers and their 18-month old infants
      completed the Strange Situation (SS) procedure to elicit attachment behaviors.
      During a separate functional MRI session, mothers were exposed to their own
      infant's cry sound, as well as an unfamiliar infant's cry and control sound.
      Maternal neural response to own infant cry related to both overall attachment
      security and specific infant behaviors. Mothers of less secure infants maintained
      greater activation to their cry in left parahippocampal and amygdala regions and
      the right posterior insula consistent with a negative schematic response bias.
      Mothers of infants exhibiting more avoidant or contact maintaining behaviors
      during the SS showed diminished response across left prefrontal, parietal, and
      cerebellar areas involved in attentional processing and cognitive control.
      Mothers of infants exhibiting more disorganized behavior showed reduced response
      in bilateral temporal and subcallosal areas relevant to social cognition and
      emotion regulation. No differences by attachment classification were found.
      Implications for attachment transmission models are discussed.

PMID- 22982279
TI  - Full-term and very-low-birth-weight preterm infants' self-regulating behaviors
      during a Still-Face interaction: influences of maternal touch.
AB  - The present study was designed to examine maternal touch and infants' self
      regulating behavior in full-term and very-low-birth-weight preterm (VLBW/PT)
      infant-mother dyads. Mothers and their 51/2-month-old full-term (n=40) and
      VLBW/PT (n=40) infants participated in a Still-Face (SF) procedure. Mothers used
      high levels of touching (82% of the interaction) and the functions of touch
      changed across periods. More attention-getting touch was used during the Normal
      period and more nurturing and playful touch during the Reunion Normal period.
      Mothers of VLBW/PT infants engaged in more playful touch across periods. Similar
      amounts of self-regulatory behaviors were observed for both groups across all
      three periods; however, full-term infants exhibited greater self-comfort
      regulatory behaviors during the Reunion Normal period. Finally, for both groups
      the presence and quality of maternal touch were associated with infants' self
      regulating behavior; thus providing evidence for the regulatory roles of maternal
      touch. These findings underscore how both maternal touch and infants' self
      regulating behaviors are important and effective components of infants' emotion
      regulation.

PMID- 22982280
TI  - Individual differences in what 2-year-old children look at: observations in a
      daycare.
AB  - The directions of gazes of six children were observed at the ages of 24, 30 and
      36 months during free-time play in a group nursing situation. The study found
      that there were two types of looking behaviour among children. One type of
      looking behaviour was characterized by a tendency not to focus and gazing on
      people, whereas the other type characterized by a preference to focus and gaze at
      both objects and people. Considering the fact that looking tendencies of young
      children are related to social behaviours, individual differences in looking
      behaviour among children that were observed in this study could influence their
      interactions with surrounding people.

PMID- 22982281
TI  - Infant humor perception from 3- to 6-months and attachment at one year.
AB  - Infancy is a critical time for the development of secure attachment, which is
      facilitated by emotionally synchronous interactions with parents. Humor
      development, which includes shared laughter and joint attention to an event,
      emerges concurrently with attachment, but little is known regarding the
      relationship, if any, between humor development and attachment in the first year.
      Thirty 3-month-old infants were videoed at home each month until they were 6
      months old while their parents attempted to amuse them. Frequency of infants'
      smiles and laughs served as a measure of "state humor", and the smiling/laughing
      subscale of the Infant Behavior Questionnaire-Revised served as a measure of
      "trait humor". State and trait humor were not correlated. Lower trait humor as 6
      months predicted higher attachment security on the Attachment Q-sort at 12-months
      (r=.46), suggesting that less good-humored infants elicit greater parental
      engagement, which works to the benefit of attachment, or vice versa. Future
      studies should examine the importance of smiling and laughter as they relate to
      other developmental phenomena in the first year.

PMID- 22982282
TI  - Maternal depression and sex differences shape the infants' trajectories of
      cognitive development.
AB  - The effect of maternal depression on the trajectories of cognitive development
      was studied in 26 infants with depressed mothers as compared to a group of 24
      infants with non-depressed mothers. The infants were tested on Mullen Scales of
      Early Learning when they were 6, 12 and 18 months old. Mothers reported their
      depressive symptoms over the follow ups. The study also investigated if there
      were sex differences in the cognitive trajectories. Multilevel modeling analyses
      revealed that infants of depressed mothers had a stable lower cognitive score
      over the period 6-18 months of age as compared to the infants of non-depressed
      mothers, and that the girls tended to increase their cognitive scores as compared
      to the boys over the same time period. The results are discussed in light of the
      stability of depression symptoms over the follow up and sex differences in
      cognitive development.

PMID- 22982283
TI  - Short-term experience increases infants' sensitivity to audiovisual asynchrony.
AB  - The present study explored the effects of short-term experience with audiovisual
      asynchronous stimuli in 6-month-old infants. Results revealed that, in contrast
      with adults (usually showing temporal recalibration under similar circumstances),
      a brief exposure to asynchrony increased infants' perceptual sensitivity to
      audiovisual synchrony.

PMID- 22982284
TI  - Differential distribution and lateralization of infant gestures and their
      relation to maternal gestures in the Face-to-Face Still-Face paradigm.
AB  - We examined whether there are differences in the lateralization of expressive
      gestures in infants during normal and stressful interactions with their mothers
      and the relations between their gestures. Thirty full-term 6-12 month-old infants
      were videotaped during the Face-to-Face Still-Face paradigm. We coded the
      occurrence and lateralization of infant self-directed and other-directed gestures
      and maternal proximal and distal gestures. Infant self-directed gestures
      increased from the Play to Still-Face episode and decreased from the Still-Face
      to Reunion episode. Other-directed gestures decreased from the Play to Still-Face
      and increased from the Still-Face to Reunion episode. During the Still-Face, self
      directed gestures were predominantly performed with the left side of the body.
      Maternal gestures were not lateralized, but there was a prevalence of distal
      gestures in the Play and Reunion episodes of the paradigm. Left-sided infant
      other-directed gestures and left-sided maternal gestures were associated with
      each other. The findings highlight a differential utilization and lateralization
      of self- and other-directed gestures related to context and the stress
      experienced by the infant as well as to maternal gestures. These results are
      suggestive of a brain asymmetry, but an asymmetry related to emotional engagement
      and stress regulation.

PMID- 22982286
TI  - Individual differences in the prevalence of words and gestures in the second year
      of life: developmental trends in Italian children.
AB  - This longitudinal study investigated individual differences in the relationship
      between words and representational gestures in a sample of 104 Italian children
      between 12 and 23 months of age, using two parent-report questionnaires.
      Multivariate analyses reached three main conclusions. First, a high gesture
      frequency did not enhance language development when word production was equated
      and children showing a prevalence of words over gestures outperformed those
      showing a prevalence of gestures over words at all ages. Second, an early
      predominance of gestures at 12 months did not hamper the acquisition of verbal
      abilities, while the persistence of a gestural advantage at 16 and 20 months was
      related to a slower language development at 23 months. Finally, for infants with
      small gestural repertoires at 12 months, a high frequency of gesture use
      benefitted the process of lexical learning. These findings support the hypothesis
      that representational gestures bridge the transition from pre-linguistic to
      symbolic communication. However, they also suggest that the role of
      representational gestures might be less critical than previously proposed, being
      mostly evident in the earlier phases of the second year of life.

PMID- 22982285
TI  - Relation between early motor delay and later communication delay in infants at
      risk for autism.
AB  - BACKGROUND: Motor delays have been reported in retrospective studies of young
      infants who later develop Autism Spectrum Disorders (ASDs). OBJECTIVE: In this
      study, we prospectively compared the gross motor development of a cohort at risk
      for ASDs; infant siblings of children with ASDs (AU sibs) to low risk typically
      developing (LR) infants. METHODS: 24 AU sibs and 24 LR infants were observed at 3
      and 6 months using a standardized motor measure, the Alberta Infant Motor Scale
      (AIMS). In addition, as part of a larger study, the AU sibs also received a
      follow-up assessment to determine motor and communication performance at 18
      months using the Mullen Scales of Early Learning. RESULTS: Significantly more AU
      sibs showed motor delays at 3 and 6 months than LR infants. The majority of the
      AU sibs showed both early motor delays and later communication delays.
      LIMITATIONS: Small sample size and limited follow-up. CONCLUSIONS: Early motor
      delays are more common in AU sibs than LR infants. Communication delays later
      emerged in 67-73% of the AU sibs who had presented with early motor delays.
      Overall, early motor delays may be predictive of future communication delays in
      children at risk for autism.

PMID- 22982287
TI  - Differential ethnic associations between maternal flexibility and play
      sophistication in toddlers born very low birth weight.
AB  - Children born very low birth weight (<1500 g, VLBW) are at increased risk for
      developmental delays. Play is an important developmental outcome to the extent
      that child's play and social communication are related to later development of
      self-regulation and effective functional skills, and play serves as an important
      avenue of early intervention. The current study investigated associations between
      maternal flexibility and toddler play sophistication in Caucasian, Spanish
      speaking Hispanic, English speaking Hispanic, and Native American toddlers (18-22
      months adjusted age) in a cross-sectional cohort of 73 toddlers born VLBW and
      their mothers. We found that the association between maternal flexibility and
      toddler play sophistication differed by ethnicity (F(3,65) = 3.34, p = .02). In
      particular, Spanish speaking Hispanic dyads evidenced a significant positive
      association between maternal flexibility and play sophistication of medium effect
      size. Results for Native Americans were parallel to those of Spanish speaking
      Hispanic dyads: the relationship between flexibility and play sophistication was
      positive and of small-medium effect size. Findings indicate that for Caucasians
      and English speaking Hispanics, flexibility evidenced a non-significant (negative
      and small effect size) association with toddler play sophistication. Significant
      follow-up contrasts revealed that the associations for Caucasian and English
      speaking Hispanic dyads were significantly different from those of the other two
      ethnic groups. Results remained unchanged after adjusting for the amount of
      maternal language, an index of maternal engagement and stimulation; and after
      adjusting for birth weight, gestational age, gender, test age, cognitive ability,
      as well maternal age, education, and income. Our results provide preliminary
      evidence that ethnicity and acculturation may mediate the association between
      maternal interactive behavior such as flexibility and toddler developmental
      outcomes, as indexed by play sophistication. Addressing these association
      differences is particularly important in children born VLBW because interventions
      targeting parent interaction strategies such as maternal flexibility must account
      for ethnic-cultural differences in order to promote toddler developmental
      outcomes through play paradigms.

PMID- 22982288
TI  - Dynamics of N-person snowdrift games in structured populations.
AB  - In many real-life situations, the completion of a task by a group toward
      achieving a common goal requires the cooperation of at least some of its members,
      who share the required workload. Such cases are conveniently modeled by the N
      person snowdrift game, an example of a Public Goods Game. Here we study how an
      underlying network of contacts affects the evolutionary dynamics of collective
      action modeled in terms of such a Public Goods Game. We analyze the impact of
      different types of networks in the global, population-wide dynamics of
      cooperators and defectors. We show that homogeneous social structures enhance the
      chances of coordinating toward stable levels of cooperation, while heterogeneous
      network structures create multiple internal equilibria, departing significantly
      from the reference scenario of a well-mixed, structureless population.

PMID- 22982289
TI  - Reduction techniques for network validation in systems biology.
AB  - The rapidly increasing amount of experimental biological data enables the
      development of large and complex, often genome-scale models of molecular systems.
      The simulation and analysis of these computer models of metabolism, signal
      transduction, and gene regulation are standard applications in systems biology,
      but size and complexity of the networks limit the feasibility of many methods.
      Reduction of networks provides a hierarchical view of complex networks and gives
      insight knowledge into their coarse-grained structural properties. Although
      network reduction has been extensively studied in computer science, adaptation
      and exploration of these concepts are still lacking for the analysis of
      biochemical reaction systems. Using the Petri net formalism, we describe two
      local network structures, common transition pairs and minimal transition
      invariants. We apply these two structural elements for network reduction. The
      reduction preserves the CTI-property (covered by transition invariants), which is
      an important feature for completeness of biological models. We demonstrate this
      concept for a selection of metabolic networks including a benchmark network of
      Saccharomyces cerevisiae whose straightforward treatment is not yet feasible even
      on modern supercomputers.

PMID- 22982290
TI  - The reconstructed evolutionary process with the fossil record.
AB  - Using the fossil record yields more detailed reconstructions of the evolutionary
      process than what is obtained from contemporary lineages only. In this work, we
      present a stochastic process modeling not only speciation and extinction, but
      also fossil finds. Next, we derive an explicit formula for the likelihood of a
      reconstructed phylogeny with fossils, which can be used to estimate the
      speciation and extinction rates. Finally, we provide a comparative simulation
      based evaluation of the accuracy of estimations of these rates from complete
      phylogenies (including extinct lineages), from reconstructions with contemporary
      lineages only and from reconstructions with contemporary lineages and the fossil
      record. Results show that taking the fossil record into account yields more
      accurate estimates of speciation and extinction rates than considering only
      contemporary lineages.

PMID- 22982291
TI  - A spatial physiological model for p53 intracellular dynamics.
AB  - In this paper we design and analyse a physiologically based model representing
      the accumulation of protein p53 in the nucleus after triggering of ATM by DNA
      damage. The p53 protein is known to have a central role in the response of the
      cell to cytotoxic or radiotoxic insults resulting in DNA damage. A reasonable
      requirement for a model describing intracellular signalling pathways is taking
      into account the basic feature of eukaryotic cells: the distinction between
      nucleus and cytoplasm. Our aim is to show, on a simple reaction network
      describing p53 dynamics, how this basic distinction provides a framework which is
      able to yield expected oscillatory dynamics without introducing either positive
      feedbacks or delays in the reactions. Furthermore we prove that oscillations
      appear only if some spatial constraints are respected, e.g. if the diffusion
      coefficients correspond to known biological values. Finally we analyse how the
      spatial features of a cell influence the dynamic response of the p53 network to
      DNA damage, pointing out that the protein oscillatory dynamics is indeed a
      response that is robust towards changes with respect to cellular environments.
      Even if we change the cell shape or its volume or better its ribosomal
      distribution, we observe that DNA damage yields sustained oscillations of p53.

PMID- 22982292
TI  - Structural analysis of the quaking homodimerization interface.
AB  - Quaking (QkI) is a prototypical member of the STAR (signal transducer and
      activator of RNA) protein family, which plays key roles in posttranscriptional
      gene regulation by controlling mRNA translation, stability and splicing. QkI-5
      has been shown to regulate mRNA expression in the central nervous system, but
      little is known about its roles in other tissues. STAR proteins function as
      dimers and bind to bipartite RNA sequences; however, the structural and
      functional roles of homodimerization and heterodimerization are still unclear.
      Here, we present the crystal structure of the QkI dimerization domain, which
      adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 (germ
      line development defective-1) and Sam68 (Src-associated protein during mitosis,
      68kDa) but differs by an additional helix inserted in the dimer interface.
      Variability of the dimer interface residues likely ensures selective
      homodimerization by preventing association with non-cognate STAR family proteins
      in the cell. Mutations that inhibit dimerization also significantly impair RNA
      binding in vitro, alter QkI-5 protein levels and impair QkI function in a
      splicing assay in vivo. Together, our results indicate that a functional Qua1
      homodimerization domain is required for QkI-5 function in mammalian cells.

PMID- 22982293
TI  - Ligand-induced structural changes in the Escherichia coli ferric citrate
      transporter reveal modes for regulating protein-protein interactions.
AB  - Outer-membrane TonB-dependent transporters, such as the Escherichia coli ferric
      citrate transporter FecA, interact with the inner-membrane protein TonB through
      an energy-coupling segment termed the Ton box. In FecA, which regulates its own
      transcription, the Ton box is preceded by an N-terminal extension that interacts
      with the inner-membrane protein FecR. Here, site-directed spin labeling was used
      to examine the structural basis for transcriptional signaling and Ton box
      regulation in FecA. EPR spectroscopy indicates that regions of the N-terminal
      domain are in conformational exchange, consistent with its role as a protein
      binding element; however, the local fold and dynamics of the domain are not
      altered by substrate or TonB. Distance restraints derived from pulse EPR were
      used to generate models for the position of the extension in the apo, substrate-,
      and TonB-bound states. In the apo state, this domain is positioned at the
      periplasmic surface of FecA, where it interacts with the Ton box and blocks
      access of the Ton box to the periplasm. Substrate addition rotates the
      transcriptional domain and exposes the Ton box, leading to a disorder transition
      in the Ton box that may facilitate interactions with TonB. When a soluble
      fragment of TonB is bound to FecA, the transcriptional domain is displaced to one
      edge of the barrel, consistent with a proposed beta-strand exchange mechanism.
      However, neither substrate nor TonB displaces the N-terminus further into the
      periplasm. This result suggests that the intact TonB system mediates both
      signaling and transport by unfolding portions of the transporter.

PMID- 22982294
TI  - Epitope-specific immune tolerization ameliorates experimental autoimmune
      encephalomyelitis.
AB  - The availability of glatiramer acetate (GA) for inducing immune tolerance is a
      significant advancement in the treatment of multiple sclerosis (MS). However, a
      sizable proportion of patients maintain active disease, regardless of treatment.
      Another approach to induce T-cell tolerance is therefore still an unmet medical
      need. We hypothesized that induction of mucosal tolerance toward a pro
      inflammatory T-cell epitope derived from a heat shock protein (HSP) (RatP2) could
      translate into clinical benefit. We found that treatment of experimental
      autoimmune encephalomyelitis (EAE, a model of MS) with the peptide RatP2
      determined a significant clinical improvement, which was comparable to the
      standard tolerization treatment (an MBP-derived peptide pool) and superior to GA.
      Histological analysis demonstrated a reduction of brain and spinal cord
      inflammatory lesions in treated animals. Moreover, with immunological analysis we
      identified biomarkers associated with clinical response. This work provides proof
      of-concept to support the further testing of this approach as a possible
      complement to currently available therapies for MS.

PMID- 22982295
TI  - Hepatic veno-occlusive disease with immunodeficiency (VODI): first reported case
      in the U.S. and identification of a unique mutation in Sp110.
AB  - Familial hepatic veno-occlusive disease with immunodeficiency (VODI, OMIM:
      235550), a rare form of severe combined immune deficiency, was first described in
      Australian Lebanese patients as being associated with homozygous mutations in
      SP110, a gene encoding a PML nuclear body-associated protein. We present the
      first case of confirmed VODI in the United States, and identify the first novel
      missense mutation in SP110. The 3-year-old daughter of Hispanic parents without
      known consanguinity presented at age 5 months with fever, hepatomegaly, and
      pancytopenia. Her brother died at age 3 months from hepatic failure of
      undetermined etiology. Initial T- and B-cell counts were low, but eventually
      normalized. Serum IgG and IgM levels were low for age. Lymphoproliferation to
      mitogens and allogenic B-cells was normal, but absent to tetanus and candida
      antigens. Serum antibody levels against pneumococcal, Hib and tetanus antigens
      were low. Liver biopsies at ages 5 and 9 months were consistent with hepatic veno
      occlusive disease or hVOD (also known as sinusoidal obstruction syndrome or SOS)
      and broncho-alveolar lavage detected Pneumocystis jiroveci. The patient recovered
      from her acute disease and has been clinically stable on immunoglobulin
      replacement therapy and trimethoprim-sulfamethoxazole prophylaxis. T-Cell
      receptor excision circle (TREC) analysis suggests that VODI will not be detected
      by newborn screening for severe combined immunodeficiency that relies on this
      assay. DNA was obtained from the patient, 4 siblings, and both parents, and SP110
      was sequenced. The first missense mutation, a homozygous deletion/insertion
      variation in exon 2 (NM_080424.2 (SP110):c.78_79delinsAT) was detected in the
      patient. This novel mutation segregated in the heterozygous state in other living
      unaffected family members. The mechanism by which this SP110 mutation associates
      with VODI is consistent with the normal length mutated SP110 protein being
      subject to enhanced proteosome degradation resulting in marked reductions in
      SP110 protein.

PMID- 22982297
TI  - Assessment of MDA efficiency for genotyping using cloned embryo biopsies.
AB  - The possibility to genotype embryos prior to implantation would have advantages
      for increasing the speed of selection of cattle. Reliable genotyping requires
      more DNA than can be obtained from biopsies of embryos, if they are to remain
      viable. Multiple displacement amplification (MDA) is a whole genome amplification
      technique used to increase the amount of DNA from biopsies for analysis. Reduced
      genome coverage resulting in Allele Drop Out (ADO) at heterozygous loci or
      missing genotypes are drawbacks of MDA. The present article describes the
      correlation between the input DNA quantity or embryo biopsy size and MDA success.
      Missing genotypes and ADO drastically increased when fewer than 30-40 cells or
      the genomic equivalents were used. However, embryo viability was found to be
      reduced if biopsied with more than 10 cells. Therefore, in vitro cell culture was
      investigated as a means to increase the number of cells available and the
      genotyping reliability.

PMID- 22982296
TI  - Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic
      serum nephritis.
AB  - Previously it was shown that the TNF superfamily member TWEAK (TNFSF12) acts
      through its receptor, Fn14, to promote proinflammatory responses in kidney cells,
      including the production of MCP-1, RANTES, IP-10 and KC. In addition, the
      TWEAK/Fn14 pathway promotes mesangial cell proliferation, vascular cell
      activation, and renal cell death. To study the relevance of the TWEAK/Fn14
      pathway in the pathogenesis of antibody-induced nephritis using the mouse model
      of nephrotoxic serum nephritis (NTN), we induced NTN by passive transfer of
      rabbit anti-glomerular antibodies into Fn14 knockout (KO) and wild type (WT)
      mice. Severe proteinuria as well as renal histopathology were induced in WT but
      not in Fn14 KO mice. Similarly, a pharmacologic approach of anti-TWEAK mAb
      administration into WT mice in the NTN model significantly ameliorated
      proteinuria and improved kidney histology. Anti-TWEAK treatment did not affect
      the generation of mouse anti-rabbit antibodies; however, within the kidney there
      was a significant decrease in glomerular immunoglobulin deposition, as well as
      macrophage infiltrates and tubulointerstitial fibrosis. The mechanism of action
      is most likely due to reductions in downstream targets of TWEAK/Fn14 signaling,
      including reduced renal expression of MCP-1, VCAM-1, IP-10, RANTES as well as
      Fn14 itself, and other molecular pathways associated with fibrosis in anti-TWEAK
      treated mice. Thus, TWEAK/Fn14 interactions are instrumental in the pathogenesis
      of nephritis in the NTN model, apparently mediating a cascade of pathologic
      events locally in the kidney rather than by impacting the systemic immune
      response. Disrupting TWEAK/Fn14 interactions may be an innovative kidney
      protective approach for the treatment of lupus nephritis and other antibody
      induced renal diseases.

PMID- 22982298
TI  - Upregulation of anti-apoptotic factors in upper motor neurons after spinal cord
      injury in adult zebrafish.
AB  - Unlike mammals, fish motor function can recover within 6-8weeks after spinal cord
      injury (SCI). The motor function of zebrafish is regulated by dual control; the
      upper motor neurons of the brainstem and motor neurons of the spinal cord. In
      this study, we aimed to investigate the framework behind the regeneration of
      upper motor neurons in adult zebrafish after SCI. In particular, we investigated
      the cell survival of axotomized upper motor neurons and its molecular machinery
      in zebrafish brain. As representative nuclei of upper motor neurons, we
      retrogradely labeled neurons in the nucleus of medial longitudinal fasciculus
      (NMLF) and the intermediate reticular formation (IMRF) using a tracer injected
      into the lesion site of the spinal cord. Four to eight neurons in each thin
      sections of the area of NMLF and IMRF were successfully traced at least 1-15days
      after SCI. TUNEL staining and BrdU labeling assay revealed that there was no
      apoptosis or cell proliferation in the axotomized neurons of the brainstem at
      various time points after SCI. In contrast, axotomized neurons labeled with a
      neurotracer showed increased expression of anti-apoptotic factors, such as Bcl-2
      and phospho-Akt (p-Akt), at 1-6days after SCI. Such a rapid increase of Bcl-2 and
      p-Akt protein levels after SCI was quantitatively confirmed by western blot
      analysis. These data strongly indicate that upper motor neurons in the NMLF and
      IMRF can survive and regrow their axons into the spinal cord through the rapid
      activation of anti-apoptotic molecules after SCI. The regrowing axons from upper
      motor neurons reached the lesion site at 10-15days and then crossed at 4-6weeks
      after SCI. These long-distance descending axons from originally axotomized
      neurons have a major role in restoration of motor function after SCI.

PMID- 22982299
TI  - Metal dyshomeostasis and oxidative stress in Alzheimer's disease.
AB  - Alzheimer's disease is the leading cause of dementia in the elderly and is
      defined by two pathological hallmarks; the accumulation of aggregated amyloid
      beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's
      disease progression is still debated, however, increased oxidative stress is an
      early and sustained event that underlies much of the neurotoxicity and consequent
      neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron
      promote amyloid beta oligomer formation. Additionally, copper and iron are redox
      active and can generate reactive oxygen species via Fenton (and Fenton-like
      chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally
      abundant in the brain but Alzheimer's disease brain contains elevated
      concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta
      can become pro-oxidant and when complexed to copper or iron it can generate
      hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron
      homeostasis may become perturbed in Alzheimer's disease and could underlie an
      increased oxidative stress burden. In this review we discuss
      oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that
      metals play in this process. Recent studies have started to elucidate molecular
      links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we
      discuss metal binding compounds that are designed to cross the blood brain
      barrier and restore metal homeostasis as potential Alzheimer's disease
      therapeutics.

PMID- 22982300
TI  - Astrocyte functions in the copper homeostasis of the brain.
AB  - Copper is an essential element that is required for a variety of important
      cellular functions. Since not only copper deficiency but also excess of copper
      can seriously affect cellular functions, the cellular copper metabolism is
      tightly regulated. In brain, astrocytes appear to play a pivotal role in the
      copper metabolism. With their strategically important localization between
      capillary endothelial cells and neuronal structures they are ideally positioned
      to transport copper from the blood-brain barrier to parenchymal brain cells.
      Accordingly, astrocytes have the capacity to efficiently take up, store and to
      export copper. Cultured astrocytes appear to be remarkably resistant against
      copper-induced toxicity. However, copper exposure can lead to profound
      alterations in the metabolism of these cells. This article will summarize the
      current knowledge on the copper metabolism of astrocytes, will describe copper
      induced alterations in the glucose and glutathione metabolism of astrocytes and
      will address the potential role of astrocytes in the copper metabolism of the
      brain in diseases that have been connected with disturbances in brain copper
      homeostasis.

PMID- 22982301
TI  - Molecular characteristics of Chinese patients with Rett syndrome.
AB  - OBJECTIVE: Rett syndrome (RTT) is a neurodevelopmental disorder which affects
      1/10,000 girls. The aim of this study is to delineate the molecular
      characteristics of Rett syndrome in China based on the largest group of Chinese
      patients ever studied. METHODS: In all, 365 Chinese patients with Rett syndrome
      were recruited. Clinical information including the family reproductive history
      was collected through interviewing patients and their parents as well as
      questionnaires. MECP2, CDKL5, FOXG1 mutational analysis was performed using
      polymerase chain reaction (PCR), direct sequencing and multiplex ligation
      dependent probe amplification (MLPA). The parental origin of mutated MECP2 gene,
      the MECP2 gene mutation rate in the patients' mothers, and the X-chromosome
      inactivation pattern of the mothers who carry the mutation were also analyzed.
      RESULTS: Almost all of the patients were sporadic cases except one pair of twins.
      The pregnancy loss in probands' mothers and sex ratio of offspring in probands(')
      generation were available in 352 families and were comparable to the general
      population. Out of the 365 cases, 315 had MECP2 gene mutations and 3 had de novo
      CDKL5 gene mutations. No patients had FOXG1 mutation. Among the 315 cases with
      MECP2 mutations, 274 were typical cases and 41 were atypical cases. All the 3
      cases with CDKL5 gene mutations were atypical RTT with early-onset seizures. The
      analysis of parental origin of mutated MECP2 gene were performed on 139 cases, 90
      (64.7%) cases were informative for the study. The result showed 94.4% cases with
      mutations from paternal origin and 5.6% from maternal origin. Among the cases
      with paternal mutation, 90.6% had point mutations. C > T was the most common one,
      accounting for 85.7% of the point mutations. Only one normal phenotype mother
      (0.41%) carried the same p.R133C mutation of MECP2 gene as her daughter with mild
      phenotype. The different patterns of X-chromosome inactivation in the mother and
      the daughter may explain their different phenotypes. CONCLUSION: The high rate of
      paternal origin of the mutated MECP2 gene may explain the high occurrence of RTT
      in female gender. The family cases of RTT are rare and the recurrence risk of RTT
      is very low in China. Only 0.41% (1/244) mothers carry the pathogenic gene. FOXG1
      mutations were not found in this group of Chinese patients.

PMID- 22982302
TI  - A chemistry wiki to facilitate and enhance compound design in drug discovery.
AB  - At AstraZeneca a focus on hypothesis-driven design and the formation of drug
      design teams has placed a greater emphasis on collaboration in the drug discovery
      process. We have created a novel software tool based on the principles of wikis
      and social networks to facilitate collaborative working, visual planning and
      incorporation of predictive science to improve design capability. Monitoring the
      design and make process via the tool enabled the identification of bottlenecks
      and delays. Solutions to these problems were implemented, reducing the time taken
      from the initial idea stage to the generation of the synthesised compound by more
      than 50%.

PMID- 22982304
TI  - Are alsin and spartin novel interaction partners?
AB  - Mutations in ALS2 gene/alsin are associated with recessive forms of motor neuron
      disorders including Juvenile Amyotrophic Lateral Sclerosis (JALS), Infantile
      onset Ascending Hereditary Spastic Paraplegia (IAHSP) and Juvenile Primary
      Lateral Sclerosis (JPLS). In this study, we show that alsin and another MND
      linked protein, spartin are related to each other both at mRNA and protein levels
      in Neuro2a cells. We observed significant alterations in spartin expression in
      alsin knock-down conditions. We further found that both proteins colocalize in
      N2a cells and spartin isoform-a precipitates with alsin in the same protein
      complex. In the light of these results we suggest that alsin and spartin may
      interact each other physically.

PMID- 22982305
TI  - Cooperation between two ClpB isoforms enhances the recovery of the recombinant
      beta-galactosidase from inclusion bodies.
AB  - Bacterial ClpB is a molecular chaperone that solubilizes and reactivates
      aggregated proteins in cooperation with the DnaK chaperone system. The mechanism
      of protein disaggregation mediated by ClpB is linked to translocation of
      substrates through the central channel within the ring-hexameric structure of
      ClpB. Two isoforms of ClpB are produced in vivo: the full-length ClpB95 and the
      truncated ClpB80 (ClpBDeltaN), which does not contain the N-terminal domain. The
      functional specificity of the two ClpB isoforms and the biological role of the N
      terminal domain are still not fully understood. Recently, it has been
      demonstrated that ClpB may achieve its full potential as an aggregate
      reactivating chaperone through the functional interaction and synergistic
      cooperation of its two isoforms. It has been found that the most efficient
      resolubilization and reactivation of stress-aggregated proteins occurred in the
      presence of both ClpB95 and ClpB80. In this work, we asked if the two ClpB
      isoforms functionally cooperate in the solubilization and reactivation of
      proteins from insoluble inclusion bodies (IBs) in Escherichia coli cells. Using
      the model beta-galactosidase fusion protein (VP1LAC), we found that
      solubilization and reactivation of enzymes entrapped in IBs occurred more
      efficiently in the presence of ClpB95 with ClpB80 than with either ClpB95 or
      ClpB80 alone. The two isoforms of ClpB chaperone acting together enhanced the
      solubility and enzymatic activity of beta-galactosidase sequestered into IBs.
      Both ClpB isoforms were associated with IBs of beta-galactosidase, what
      demonstrates their affinity to this type of aggregates. These results demonstrate
      a synergistic cooperation between the two isoforms of ClpB chaperone. In
      addition, no significant recovery of the beta-galactosidase from IBs in DeltaclpB
      mutant cells suggests that ClpB is a key chaperone in IB protein release.

PMID- 22982303
TI  - Biomarkers of Parkinson's disease: current status and future perspectives.
AB  - This review summarizes major advances in biomarker discovery for diagnosis,
      differential diagnosis and progression of Parkinson's disease (PD), with emphasis
      on neuroimaging and biochemical markers. Potential strategies to develop
      biomarkers capable of predicting PD in the prodromal stage before the appearance
      of motor symptoms or correlating with nonmotor symptoms, an active area of
      research, are also discussed.

PMID- 22982306
TI  - Estrogen induced beta-1,4-galactosyltransferase 1 expression regulates
      proliferation of human breast cancer MCF-7 cells.
AB  - Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose beta-1,4-N
      acetylglucosamine (Galbeta1-4GlcNAc) groups on N-linked sugar chains of
      glycoproteins, which play important roles in many biological events, including
      the proliferation and migration of cancer cells. A previous microarray study
      reported that this gene is expressed by estrogen treatment in breast cancer. In
      this study, we examined the regulatory mechanisms and biological functions of
      estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced
      expression of B4GALT1 is localized in intracellular compartments and in the
      plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the
      production of the Galbeta1-4GlcNAc structure. The result from a promoter assay
      and chromatin immunoprecipitation revealed that 3 different estrogen response
      elements (EREs) in the B4GALT1 promoter are critical for responsiveness to
      estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-alpha-ERE
      binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However,
      the inhibition of signal molecules relating to the extra-nuclear pathway,
      including the G-protein coupled receptors, Ras, and mitogen-activated protein
      kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the
      B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the
      significant inhibition of estrogen-induced proliferation of MCF-7 cells.
      Considering these results, we propose that estrogen regulates the expression of
      B4GALT1 through the direct binding of ER-alpha to ERE and that the expressed
      B4GALT1 plays a crucial role in the proliferation of MCF-7 cells through its
      activity as a membrane receptor.

PMID- 22982307
TI  - Macrophage inflammatory protein-2 (MIP-2)/CXCR2 blockade attenuates acute graft
      versus-host disease while preserving graft-versus-leukemia activity.
AB  - Allogenic bone marrow transplantation (BMT), an important treatment for
      hematological malignancies, is often complicated by graft-versus-host disease
      (GVHD). Suppression of GVHD is associated with the unwanted diminishment of the
      graft-versus-leukemia (GVL) response. The aim of this study was to maintain the
      benefits of GVL during GVHD suppression through isolated blockade of T-cell
      migration factors. To this end, we developed a murine model of B-cell leukemia,
      which was treated with BMT to induce GVHD. Within this model, functional blockade
      of MIP-2/CXCR2 was analyzed by observing proteomic, histologic and clinical
      variables of GVHD manifestation. Luminex assay of collected tissue identified
      several cytokines [granulocyte colony-stimulating factor (G-CSF), keratinocyte
      derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2), and
      interleukin-23 (IL-23)] that were upregulated during GHVD, but reduced by
      neutralizing the MIP-2/CXCR2 axis. In addition, donor T-cell blockade of CXCR2
      combined with recipient administration of anti-MIP-2 caused a significant
      decrease in GVHD while preserving the GVL response. We propose that blocking the
      MIP-2/CXCR2 axis represents a novel strategy to separate the toxicity of GVHD
      from the beneficial effects of GVL after allogenic BMT.

PMID- 22982308
TI  - SiRNAs conjugated with aromatic compounds induce RISC-mediated antisense strand
      selection and strong gene-silencing activity.
AB  - Short interference RNA (siRNA) is a powerful tool for suppressing gene expression
      in mammalian cells. In this study, we focused on the development of siRNAs
      conjugated with aromatic compounds in order to improve the potency of RNAi and
      thus to overcome several problems with siRNAs, such as cellular delivery and
      nuclease stability. The siRNAs conjugated with phenyl, hydroxyphenyl, naphthyl,
      and pyrenyl derivatives showed strong resistance to nuclease degradation, and
      were thermodynamically stable compared with unmodified siRNA. A high level of
      membrane permeability in HeLa cells was also observed. Moreover, these siRNAs
      exhibited enhanced RNAi efficacy, which exceeded that of locked nucleic acid
      (LNA)-modified siRNAs, against exogenous Renilla luciferase in HeLa cells. In
      particular, abundant cytoplasmic localization and strong gene-silencing efficacy
      were found in the siRNAs conjugated with phenyl and hydroxyphenyl derivatives.
      The novel siRNAs conjugated with aromatic compounds are promising candidates for
      a new generation of modified siRNAs that can solve many of the problems
      associated with RNAi technology.

PMID- 22982309
TI  - Modeling the Zn(2+) and Cd(2+) metalation mechanism in mammalian metallothionein
      1a.
AB  - Mammalian metallothioneins (MTs) are a family of small cysteine rich proteins
      believed to have a number of physiological functions, including both metal ion
      homeostasis and toxic metal detoxification. Mammalian MTs bind 7 Zn(2+) or Cd(2+)
      ions into two distinct domains: an N-terminal beta-domain that binds 3 Zn(2+) or
      Cd(2+), and a C-terminal alpha-domain that binds 4 Zn(2+) or Cd(2+). Although
      stepwise metalation to the saturated M(7)-MT (where M=Zn(2+) or Cd(2+)) species
      would be expected to take place via a noncooperative mechanism involving the 20
      cysteine thiolate ligands, literature reports suggest a cooperative mechanism
      involving cluster formation prior to saturation of the protein. Electrospray
      ionization mass spectrometry (ESI-MS) provides this sensitivity through
      delineation of all species (M(n)-MT, n=0-7) coexisting at each step in the
      metalation process. We report modeled ESI-mass spectral data for the stepwise
      metalation of human recombinant MT 1a (rhMT) and its two isolated fractions for
      three mechanistic conditions: cooperative (where the binding affinities are:
      K(1)<K(2)<K(3)<...<K(7)), weakly cooperative (where K(1)=K(2)=K(3)=...=K(7)), and
      noncooperative, (where K(1)>K(2)>K(3)>...>K(7)). Detailed ESI-MS metalation data
      of human recombinant MT 1a by Zn(2+) and Cd(2+) are also reported. Comparison of
      the experimental data with the predicted mass spectral data provides conclusive
      evidence that metalation occurs in a noncooperative fashion for Zn(2+) and Cd(2+)
      binding to rhMT 1a.

PMID- 22982310
TI  - Sulforaphane induced adipolysis via hormone sensitive lipase activation,
      regulated by AMPK signaling pathway.
AB  - Sulforaphane, an aliphatic isothiocyanate derived from cruciferous vegetables, is
      known for its antidiabetic properties. The effects of sulforaphane on lipid
      metabolism in adipocytes are not clearly understood. Here, we investigated
      whether sulforaphane stimulates lipolysis. Mature adipocytes were incubated with
      sulforaphane for 24h and analyzed using a lipolysis assay which quantified
      glycerol released into the medium. We investigated gene expression of hormone
      sensitive lipase (HSL), and levels of HSL phosphorylation and AMP-activated
      protein kinase on sulforaphane-mediated lipolysis in adipocytes. Sulforaphane
      promoted lipolysis and increased both HSL gene expression and HSL activation.
      Sulforaphane suppressed AMPK phosphorylation at Thr-172 in a dose-dependent
      manner, which was associated with a decrease in HSL phosphorylation at Ser-565,
      enhancing the phosphorylation of HSL Ser-563. Taken together, these results
      suggest that sulforaphane promotes lipolysis via hormone sensitive lipase
      activation mediated by decreasing AMPK signal activation in adipocytes.

PMID- 22982311
TI  - Establishment of adipose-derived mesenchymal stem cell lines from a p53-knockout
      mouse.
AB  - Mesenchymal stem cells (MSCs) can differentiate into a variety of cell types.
      MSCs exist in several tissues such as the bone marrow, adipose, muscle,
      cartilage, and tendon. This differentiation potential makes MSCs candidates for
      cell-based therapeutic strategies for mesenchymal tissue injuries. MSCs can be
      prepared from bone marrow (BM-MSCs) and adipose (AD-MSCs); however, these MSCs
      exhibit senescence-associated growth arrest and display inevitable heterogeneity.
      We established several AD-MSC cell lines from a p53-knockout (KO) mouse. These
      cell lines were immortalized, but no cell lines grew anchorage-independently,
      suggesting that they are not cancerous. They differentiated into adipocytes,
      osteoblasts, and chondrocytes by treatment with certain stimuli. Moreover,
      following injection into the tail vein, the cells migrated into the wounded
      region of the liver and differentiated into hepatocytes. We succeeded in
      establishing several AD-MSC clonal cell lines that maintain the tissue-specific
      markers and characteristics of the developmental phase. These clonal cell lines
      will serve as important tools to study the mechanism of differentiation of MSCs.

PMID- 22982312
TI  - A mutation in Arabidopsis BSK5 encoding a brassinosteroid-signaling kinase
      protein affects responses to salinity and abscisic acid.
AB  - As the most recently characterized group of plant hormones, brassinosteroids (BR)
      are involved in a number of physiological responses. Although many key components
      of the BR signaling pathway have been isolated and characterized, there is little
      information on detailed characterization of brassinosteroid-signaling kinase
      (BSK) proteins. In this study, Arabidopsis BSK5 was isolated and functionally
      analyzed. BSK5 transcripts were detected in various tissues, and were induced by
      abiotic stresses including salt and drought, as well as phytohormones of BR and
      abscisic acid (ABA). Arabidopsis loss-of-function mutant bsk5 exhibited
      sensitivity to salinity and ABA. Mutations of the BSK5 gene also altered the
      expression of several stress-regulated genes. We suggest that BSK5 responds to
      other signals as well as BR.

PMID- 22982313
TI  - CUG binding protein 1 binds to a specific region within the human albumin 3'
      untranslated region.
AB  - 3' Untranslated regions (3'UTRs) of messenger RNAs have important roles in post
      transcriptional regulation of gene expression and this is partly achieved through
      binding of specific proteins to sequences or structures within these regions.
      Previously, replacement of a native luciferase 3'UTR with the human albumin 3'UTR
      has been found to lead to a 10-fold increase in luciferase reporter activity. In
      this work we investigated protein binding to the human albumin 3'UTR.
      Electrophoretic mobility shift and UV cross-linking assays indicate that a ~50kDa
      protein from Chinese Hamster Ovary (CHO) cells binds to the albumin 3'UTR, and
      affinity experiments followed by proteomics identified this protein as CUG
      binding protein 1 (CUG-BP1, also known as CELF1). Deletion analysis of the
      albumin 3'UTR showed that nucleotides 1-50 and nucleotides 101-150 are not
      required for binding but that removal of nucleotides 51-100 caused a loss in
      binding. The results suggest that CUG-BP1 binds to nucleotides 51-100 of the
      human albumin 3'UTR. In human cells CUG-BP1 binding may thus play a role in
      regulation of albumin expression and, additionally, it may have a function in
      post-transcriptional control in CHO cells.

PMID- 22982314
TI  - ATP activates P2X receptors to mediate gap junctional coupling in the cochlea.
AB  - ATP is an important extracellular signaling molecule and can activate both
      ionotropic (P2X) and metabotropic purinergic (P2Y) receptors to influence
      cellular function in many aspects. Gap junction is an intercellular channel and
      plays a critical role in hearing. Here, we report that stimulation of ATP reduced
      gap junctional coupling between cochlear supporting cells. This uncoupling effect
      could be evoked by nanomolar physiological levels of ATP. A P2X receptor agonist
      benzoylbenzoyl-ATP (BzATP) but not a P2Y receptor agonist UTP stimulated this
      uncoupling effect. Application of P2X receptor antagonists pyridoxalphosphate-6
      azophenyl-2',4'-disulfonic acid (PPADS, 50MUM) or oxidized ATP (oATP, 0.1mM)
      eliminated this uncoupling effect. We further found that ATP activated P2X
      receptors in the cochlear supporting cells allowing Ca(2+) influxing, thereby
      increasing intracellular Ca(2+) concentration to mediate gap junctions. These
      data suggest that ATP can mediate cochlear gap junctions at the physiological
      level by the activation of P2X receptors rather than P2Y receptors. This P2X
      receptor-mediated purinergic control on the cochlear gap junctions may play an
      important role in the regulation of K(+)-recycling for ionic homeostasis in the
      cochlea and the reduction of hearing sensitivity under noise stress for
      protection.

PMID- 22982315
TI  - Identification of the TaBTF3 gene in wheat (Triticum aestivum L.) and the effect
      of its silencing on wheat chloroplast, mitochondria and mesophyll cell
      development.
AB  - The full-length cDNA (882bp) and DNA (1742bp) sequences encoding a basic
      transcription factor 3, designated as TaBTF3, were first isolated from common
      wheat (Triticum aestivum L.). Subcellular localization studies revealed that the
      TaBTF3 protein was mainly located in the cytoplasm and nucleus. In TaBTF3
      silenced transgenic wheat seedlings obtained using the Virus-induced gene
      silencing (VIGS) method, the chlorophyll pigment content was markedly reduced.
      However, the malonaldehyde (MDA) and H(2)O(2) contents were enhanced, and the
      structure of the wheat mesophyll cell was seriously damaged. Furthermore,
      transcripts of the chloroplast- and mitochondrial-encoded genes were
      significantly reduced in TaBTF3-silenced transgenic wheat plants. These results
      suggest that the TaBTF3 gene might function in the development of the wheat
      chloroplast, mitochondria and mesophyll cell. This paper is the first report to
      describe the involvement of TaBTF3 in maintaining the normal plant mesophyll cell
      structure.

PMID- 22982316
TI  - Fibroblast growth factor 2 enhances the kinetics of mesenchymal stem cell
      chondrogenesis.
AB  - Treatment of mesenchymal stem cells (MSCs) with fibroblast growth factor 2 (FGF
      2) during monolayer expansion leads to increased expression of cartilage-related
      molecules during subsequent pellet chondrogenesis. This may be due to faster
      differentiation and/or a durable change in phenotype. In order to evaluate
      changes over time, we assessed chondrogenesis of human MSCs at early and late
      time points during pellet culture using real-time PCR, measurement of
      glycosaminoglycan accumulation, and histology. Marked enhancement of
      chondrogenesis was seen early compared to controls. However, the differences from
      controls in gene expression dramatically diminished over time. Depending on
      conditions, increases in glycosaminoglycan accumulation were maintained. These
      results suggest that FGF-2 can enhance the kinetics of MSC chondrogenesis,
      leading to early differentiation, possibly by a priming mechanism.

PMID- 22982317
TI  - Activation of AMP kinase plays a role in the increased apoptosis in the renal
      proximal tubule in cystinosis.
AB  - In cystinosis, renal proximal tubule (RPT) function is compromised, due to
      mutations in ctns, which encodes for the transporter cystinosin, which removes
      cystine from lysosomes. Altered RPT function in cystinosis has been attributed to
      decreased ATP, as well as increased apoptosis. In this report, the role of AMPK
      was examined. AMPK was activated in primary rabbit RPT cells with a cystinosin
      knockdown, using cystinosin siRNA. The activation of AMPK was associated with a
      50% decrease in ATP and a 1.7-fold increase in the ADP/ATP level. Cisplatin
      induced apoptosis also increased in primary RPT cells with a cystinosin
      knockdown. The role of AMPK in the increased sensitivity to cisplatin was
      examined. The increased sensitivity to cisplatin was prevented in primary RPT
      cells with a cystinosin knockdown by the AMPK inhibitor Compound C. The effect of
      siRNAs against AMPKalpha1 and AMPKalpha2 was also studied. The siRNAs knocked
      down AMPKalpha, and prevented AMPKalpha activation by 5-aminoimidazole-4
      carboxamide-1-beta-d-ribofuranoside (AICAR). The siRNAs against AMPKalpha1 and
      AMPKalpha2 also prevented the increased sensitivity to cisplatin in the primary
      RPT cells with a cystinosin knockdown. These results suggest that signaling
      through AMPK plays a role in the enhanced apoptosis in the RPT in cystinosis.

PMID- 22982318
TI  - Role of the Na(+)/Ca(2+) exchanger on the development of diabetes mellitus and
      its chronic complications.
AB  - Diabetes mellitus (DM) is a serious metabolic disorder with micro- and
      macrovascular complications that results in significant morbidity and mortality.
      It is well established that cytosolic Ca(2+) play an important role in
      controlling insulin secretion in pancreatic beta-cells. The Na(+)/Ca(2+)
      exchanger (NCX), an ion transport protein, is expressed in the plasma membrane of
      virtually all animal cells. NCX is a reversible carrier that can mediate the
      transport of Ca(2+) across the plasma membrane in both directions. Therefore,
      great efforts have been made to identify NCX associated with DM. NCX is expressed
      in several tissues, and acts in the protection against intracellular calcium
      overload; in the regulation of insulin secretion by beta cells, and in improving
      vascular endothelium-dependent relaxation. All these mechanisms are associated
      with DM pathogenesis and its chronic complications. Therefore, NCX is a candidate
      protein for the development of these disorders. Only a few studies investigated
      NCX in relation to chronic complications of diabetes, with inconclusive results.

PMID- 22982319
TI  - Band 4.1 proteins regulate integrin-dependent cell spreading.
AB  - Integrins link the extracellular matrix (ECM) to the cytoskeleton to control cell
      behaviors including adhesion, spreading and migration. Band 4.1 proteins contain
      4.1, ezrin, radixin, moesin (FERM) domains that likely mediate signaling events
      and cytoskeletal reorganization via integrins. However, the mechanisms by which
      Band 4.1 proteins and integrins are functionally interconnected remain enigmatic.
      Here we have investigated roles for Band 4.1 proteins in integrin-mediated cell
      spreading using primary astrocytes as a model system. We demonstrate that
      Proteins 4.1B and 4.1G show dynamic patterns of sub-cellular localization in
      astrocytes spreading on fibronectin. During early stages of cell spreading
      Proteins 4.1B and 4.1G are enriched in ECM adhesion sites but become more
      diffusely localized at later stages of spreading. Combinatorial inactivation of
      Protein 4.1B and 4.1G expression leads to impaired astrocyte spreading.
      Furthermore, in exogenous expression systems we show that the isolated Protein
      4.1 FERM domain significantly enhances integrin-mediated cell spreading. Protein
      4.1B is dispensable for reactive astrogliosis in experimental models of cortical
      injury, likely due to functional compensation by related Protein 4.1 family
      members. Collectively, these findings reveal that Band 4.1 proteins are important
      intracellular components for integrin-mediated cell spreading.

PMID- 22982320
TI  - IGF-1 prevents oxidative stress induced-apoptosis in induced pluripotent stem
      cells which is mediated by microRNA-1.
AB  - Oxidative stress contributes to tissue injury and cell death during the
      development of various diseases. The present study aims at investigating whether
      oxidative stress triggered by the exposure to hydrogen peroxide (H(2)O(2)) can
      induce apoptosis of induced pluripotent stem cells (iPS cells) in a mechanism
      mediated by insulin-like growth factor (IGF-1) and microRNA-1 (miR-1). iPS cells
      treated with H(2)O(2) showed increases in miR-1 expression, mitochondria
      dysfunction, cytochrome-c release and apoptosis, Addition of IGF-1 into the iPS
      cell cultures reduced the H(2)O(2) cytotoxicity. Prediction algorithms showed
      that 3'-untranslated regions of IGF-1 gene as a target of miR-1. Moreover, miR-1
      mimic, but not miR-1 mimic negative control, diminished the protective effect of
      IGF-1 on H(2)O(2)-induced mitochondrial dysfunction, cytochrome-c release and
      apoptosis in iPS cells. In conclusion, IGF-1 inhibits H(2)O(2)-induced
      mitochondrial dysfunction, cytochrome-c release and apoptosis. IGF-1's effect is,
      at least partially, regulated by miR-1 in iPS cells.

PMID- 22982321
TI  - Biohydrogels with magnetic nanoparticles as crosslinker: characteristics and
      potential use for controlled antitumor drug-delivery.
AB  - Hybrid magnetic hydrogels are of interest for applications in biomedical science
      as controlled drug-delivery systems. We have developed a strategy to obtain novel
      hybrid hydrogels with magnetic nanoparticles (NPs) of CoFe(2)O(3) and Fe(3)O(4)
      as crosslinker agents of carboxymethylcellulose (CMC) or hyaluronic acid (HYAL)
      polymers and we have tested these systems for controlled doxorubicin release. The
      magnetic NPs are functionalized with (3-aminopropyl)trimethoxysilane (APTMS) in
      order to introduce amino groups on the surface. The amino coating is determined
      and quantified by standard Fourier transform infrared spectroscopy and X-ray
      photoelectron spectroscopy methods, and by cyclic voltammetry, a novel approach
      that permits us to look at the solution properties of the functionalized NPs. The
      gel formation involves the creation of an amide bond between the carboxylic
      groups of CMC or HYAL and the amine groups of functionalized NPs, which work as
      crosslinking agents of the polymer chains. The hybrid hydrogels are chemically
      and morphologically characterized. The rheological and the water uptake
      properties of the hydrogels are also investigated. Under the application of an
      alternating magnetic field, the CMC-HYAL hybrid hydrogel previously loaded with
      doxorubicin shows a drug release greater than that showed by the CMC-HYAL
      hydrogel crosslinked with 1,3-diaminopropane. In conclusion, the presence of
      magnetic NPs makes the synthesized hybrid hydrogels suitable for application as a
      drug-delivery system by means of alternating magnetic fields.

PMID- 22982322
TI  - Extracellular matrix protein adsorption to phosphate-functionalized gels from
      serum promotes osteogenic differentiation of human mesenchymal stem cells.
AB  - One of the primary goals for tissue engineering is to induce new tissue formation
      by stimulating specific cell function. Human mesenchymal stem cells (hMSCs) are a
      particularly important cell type that has been widely studied for differentiation
      down the osteogenic (bone) lineage, and we recently found that simple phosphate
      functional groups incorporated into poly(ethylene glycol) (PEG) hydrogels could
      induce osteogenesis without using differentiation medium by unknown mechanisms.
      Here, we aimed to determine whether direct or indirect cell/materials
      interactions were responsible for directing hMSCs down the osteogenic lineage on
      phosphate (PO(4))-functionalized PEG hydrogels. Our results indicated that serum
      components adsorbed onto PO(4)-PEG hydrogels from medium in a presoaking step
      were sufficient for attachment and spreading of hMSCs, even when seeded in serum
      free conditions. Blocking antibodies for collagen and fibronectin (targeted to
      the hydrogel), as well as beta1 and beta3 integrin blocking antibodies (targeted
      to the cells), each reduced attachment of hMSCs to PO(4)-PEG hydrogels,
      suggesting that integrin-mediated interactions between cells and adsorbed matrix
      components facilitate attachment and spreading. Outside-in signaling, and not
      merely shape change, was found to be required for osteogenesis, as alkaline
      phosphatase activity and expression of CBFA1, osteopontin and collagen-1 were
      each significantly down regulated upon inhibition of focal adhesion kinase
      phosphorylation even though the focal adhesion structure or cell shape was
      unchanged. Our results demonstrate that complex function (i.e. osteogenic
      differentiation) can be controlled using simple functionalization strategies,
      such as incorporation of PO(4), but that the role of these materials may be due
      to more complex influences than has previously been appreciated.

PMID- 22982323
TI  - Identification of flotillin-1 as a novel biomarker for lymph node metastasis and
      prognosis of lung adenocarcinoma by quantitative plasma membrane proteome
      analysis.
AB  - To identify a novel lung adenocarcinoma (AdC) biomarker, iTRAQ-tagging combined
      with 2D LC-MS/MS analysis was used to identify differentially expressed plasma
      membrane (PM) proteins in primary lung AdCs and paraneoplastic normal lung
      tissues (PNLTs). As a result, 36 differentially expressed membrane proteins were
      identified. Two differential PM proteins flotillin-1 and caveolin-1 were
      selectively validated by Western blotting. As there has been no report on the
      association of flotillin-1 with lung AdC, immunohistochemistry was further
      performed to detect the expression of flotillin-1 in the archival tissue
      specimens including 42 cases of PNLTs, 62 cases of primary lung AdCs with lymph
      node metastasis (LNM AdCs), and 46 cases of primary lung AdCs without lymph node
      metastasis (non-LNM AdCs), and the correlation of flotillin-1 expression levels
      in lung AdCs with clinicopathological features and clinical outcomes were
      evaluated. The results showed that up-regulation of flotillin-1 expression in
      lung AdCs was significantly correlated with advanced clinical stage, lymph node
      metastasis, increased postoperative relapse and decreased overall survival. Cox
      regression analysis revealed that the expressional level of flotillin-1 was an
      independent prognostic factor. The data suggest that flotillin-1 is a potential
      novel biomarker for lymph node metastasis and prognosis of lung AdC, and
      flotillin-1 up-regulation might play an important role in the pathogenesis of
      lung AdC.

PMID- 22982324
TI  - Construction of a modular plasmid family for chromosomal integration in Bacillus
      subtilis.
AB  - The investigation of molecular processes involves the generation of knockout
      strains, the determination of promoter strength and protein overexpression. Here,
      we report the construction of the multifunctional pMG expression vector family
      for integration into the Bacillus subtilis chromosome that allows gene expression
      under single copy conditions. The pMG family enables a rapid exchange of all
      features for integration, selection and gene expression with or without N
      terminal strep-tags. This modular architecture increases the applicabilities for
      these plasmids tremendously, permitting the construction of pMG derivatives for
      chromosomal integration at versatile loci and in different Bacillus species under
      control of natural or heterologous constitutive or inducible promoters.
      Additionally, the possible replacement of the antibiotic resistance cassettes
      helps circumvent problems that arise when the use of more than three antibiotics
      is required. Furthermore, the high copy number and structural stability of the
      pUC19-based pMG vectors in Escherichia coli facilitates template production for
      target host transformation.

PMID- 22982325
TI  - Differential expression analysis of nuclear oligomerization domain proteins NOD1
      and NOD2 in orange-spotted grouper (Epinephelus coioides).
AB  - Nucleotide-binding oligomerization domain-containing proteins-1 and -2 (NOD1 and
      NOD2) are members of the NOD-like receptors (NLRs) family. They are both
      cytoplasmic receptors, and sense microbial infections/danger molecules to induce
      host innate immune response. In this study, the full-length ORF sequences of NOD1
      and NOD2 were cloned, and the putative amino acid sequences were identified in
      orange-spotted grouper (Epinephelus coioides). The complete open reading frame
      (ORF) of grouper NOD1 contained 2823 bp encoding a 940 amino acid protein.
      Grouper NOD2 cDNA contained a 2967 bp ORF, encoding a protein of 988 amino acid
      residues. Both grouper NOD1 and NOD2 had similar domains to human and fish
      counterparts. Phylogenetic tree analysis showed that grouper NOD1 clustered with
      grass carp, zebrafish and channel catfish, while NOD2 was most closely related to
      fugu. Expression patterns of grouper NOD1 and NOD2 were next studied. NOD1 had
      the highest level of expression in skin while NOD2 in trunk kidney. Post Vibrio
      alginolyticus (strain EcGS020401), lipopolysaccharide (LPS) or PolyI:C
      challenges, gene expression of grouper NOD1 and NOD2 was stimulated to different
      extents. NOD1 showed a significant enhancement after LPS stimulation, but NOD2
      increased more significantly after PolyI:C invasion, indicating that NOD1 and
      NOD2 may exert different effects on the eradication of bacteria and virus. The
      adaptor protein RIP-like-interacting CLARP kinase (RICK) and downstream molecule
      interleukin-8 (IL-8) were also induced at different levels after stimulation,
      which indicated that NOD1 and NOD2 signal transduction was involved in grouper
      innate immune protection against bacterial and viral infections.

PMID- 22982326
TI  - Salinity change impairs pipefish immune defence.
AB  - Global change is associated with fast and severe alterations of environmental
      conditions. Superimposed onto existing salinity variations in a semi-enclosed
      brackish water body such as the Baltic Sea, a decrease in salinity is predicted
      due to increased precipitation and freshwater inflow. Moreover, we predict that
      heavy precipitation events will accentuate salinity fluctuations near shore.
      Here, we investigated how the immune function of the broad-nosed pipefish
      (Syngnathus typhle), an ecologically important teleost with sex-role reversal, is
      influenced by experimentally altered salinities (control: 18 PSU, lowered: 6 PSU,
      increased: 30 PSU) upon infection with bacteria of the genus Vibrio. Salinity
      changes resulted in increased activity and proliferation of immune cells.
      However, upon Vibrio infection, individuals at low salinity were unable to mount
      specific immune response components, both in terms of monocyte and lymphocyte
      cell proliferation and immune gene expression compared to pipefish kept at
      ambient salinities. We interpret this as resource allocation trade-off, implying
      that resources needed for osmoregulation under salinity stress are lacking for
      subsequent activation of the immune defence upon infection. Our data suggest that
      composition of small coastal fish communities may change due to elevated
      environmental stress levels and the incorporated consequences thereof.

PMID- 22982327
TI  - A piscidin-like antimicrobial peptide from the icefish Chionodraco hamatus
      (Perciformes: Channichthyidae): molecular characterization, localization and
      bactericidal activity.
AB  - Antimicrobial peptides (AMPs) are considered one of the most ancient components
      of the innate immune system. They are able to exert their protection activity
      against a variety of microorganisms, and are widely distributed in both
      vertebrates and invertebrates. In this paper we focused on an AMP identified in
      the Antarctic teleost Chionodraco hamatus, an icefish species. The cDNA sequence
      of the AMP, named chionodracine, is comprised of 515 bp and translates for a
      putative protein precursor of 80 amino acids, with a signal peptide of 22 amino
      acids. The structural features evidenced in the primary sequence of chionodracine
      lead to the inclusion of the peptide in the antimicrobial family of piscidins.
      The analysis by real-time PCR of the basal gene transcripts of chionodracine in
      different icefish tissues showed that the highest expression was found in gills,
      followed by head kidney. The chionodracine expression levels in head kidney
      leukocytes were up-regulated in vitro both by LPS and poly I:C, and in vivo by
      LPS. A putative chionodracine mature peptide was synthesized and employed to
      obtain a polyclonal antiserum, which was used in immunohistochemistry of gills
      sections and revealed a significant positivity associated with mast cells. The
      bactericidal activity of the peptide was investigated and found significant
      against Antarctic psychrophilic bacteria strains (Psychrobacter sp. TAD1 and
      TA144), the Gram-positive Bacillus cereus, and at a lesser extent against the
      Gram-negative Escherichia coli. Interestingly, the haemolytic activity of
      chionodracine was tested in vitro on human erythrocytes and no significant lysis
      occurred until peptide concentration of 50 MUM.

PMID- 22982328
TI  - Cloning, characterization and expression analysis of a cold shock domain family
      member YB-1 in turbot Scophthalmus maximus.
AB  - The Y-box proteins are a family of highly conserved nucleic acid binding
      proteins. In this report we have identified a new member, YB-1 from turbot
      (Scophthalmus maximus) spleen cDNA library. The full-length cDNA sequence of
      turbot YB-1 was obtained and then the expression at transcriptional level was
      researched by qRT-PCR. In normal organs, the expression of YB-1 was higher in
      liver, brain, gill and heart, respectively. YB-1 had the highest expression level
      at gastrula stage during the early stages of embryo development. In the liver,
      kidney and spleen, the turbot YB-1 expression level was the highest at 72 h after
      challenge with lymphocystis disease virus (LCDV) and the highest at 12 h after
      challenge with Vibrio anguillarum (V. anguillarum). Furthermore, the expression
      of turbot YB-1 also distinctly increased in turbot kidney cells (TK) at 24 h
      after challenge with V. anguillarum and LCDV. These results indicated that the
      turbot YB-1 protein may play a significant role in the immune response of turbot.

PMID- 22982329
TI  - Malaysianol B, an oligostilbenoid derivative from Dryobalanops lanceolata.
AB  - A new oligostilbenoid tetramer, malaysianol B (1), was isolated from the acetone
      extract of the stem bark of Dryobalanops lanceolata along with seven
      oligostilbenoids tetramers; hopeaphenol (2), stenophyllol A (3), nepalensinol B
      (4), vaticanol B (5) and C (6), upunaphenol D (7), and flexuosol A (8). The
      structures of the isolated compounds were established on the basis of their
      spectroscopic data evidence. The antibacterial activity of the isolated compounds
      was evaluated using resazurin microtitre-plate assay.

PMID- 22982330
TI  - Isolation and free radical scavenging activities of a novel biflavonoid from the
      shells of Camellia oleifera Abel.
AB  - Oil production from the seeds of Camellia oleifera Abel. causes a great waste of
      shells which contain a lot of bioactive components. The aim of this research was
      to isolate flavonoid from the shells of C. oleifera Abel. and evaluate its uses.
      The shells were extracted by 70% methanol, hydrolyzed by 2M hydrochloric acid,
      and further crystallized in acetone, the corresponding yield of flavonoid was up
      to 2.1% (purity: 93.8%). The procedure is concise, quick and proper for
      industrial utilization of the shells. Flavonoid was identified as bimolecular
      kaempferol structure by UV, MS, (1)H NMR and (13)C NMR spectra, which is a new
      biflavonoid and first found in C. oleifera Abel. It showed stronger scavenging
      activity of DPPH and ABTS radicals than kaempferol. MDA decreased, and SOD and
      GSH-Px activities increased significantly in serum (P<0.01) and brain tissue
      (P<0.05) of mice after intragastric administration of biflavonoid at 200mg/kg/d
      for 30d. Its effects in vivo are superior to vitamin C and similar to kaempferol.
      Thus biflavonoid can be used as a prospective antioxidant to protect brain cells
      against damage from free radicals.

PMID- 22982331
TI  - Structure and antioxidant activity of polysaccharide POJ-U1a extracted by
      ultrasound from Ophiopogon japonicus.
AB  - An ultrasonic technique was employed to extract polysaccharides from Ophiopogon
      japonicus. The ultrasonic extracted polysaccharides (POJ-U) were purified, and
      POJ-U1a (a homogeneous fraction) was obtained. The structural characteristics of
      POJ-U1a were investigated by infrared spectra, gas chromatography, high
      performance liquid chromatography, periodate oxidation, Smith degradation,
      methylation analysis, gas chromatography-mass spectrometry and nuclear magnetic
      resonance spectroscopy. The results indicated that the relative molecular weight
      of POJ-U1a was 4.02*10(3)Da. POJ-U1a was an alpha-configuration polysaccharide
      with a highly branched structure, and consisted of pyranoside and funanside. The
      backbone of POJ-U1a consisted of 1,6-alpha-d-glucopyranose and 1,3,6-alpha-d
      glucofuranose in the molar ratio of 7:3, while the branched chains were mainly
      composed of 1,3-alpha-d-glucopyranose and 1-alpha-d-glucopyranose in the molar
      ratio of 1:3. The branched structure of POJ-U1a was proved intuitively by AFM.
      Significant antioxidant activity of POJ-U1a has been proved as shown by its DPPH
      radical scavenging, hydrogen radical scavenging and superoxide anion scavenging
      activities, which indicated that POJ-U1a showed strong antioxidant activity.

PMID- 22982332
TI  - Geraniin and amariin, ellagitannins from Phyllanthus amarus, protect liver cells
      against ethanol induced cytotoxicity.
AB  - Ethanol mediated free radical generation plays an important role in the
      pathogenesis of liver injuries and alcoholic liver diseases. In the present study
      two ellagitannins namely geraniin and amariin isolated from Phyllanthus amarus
      were examined for their ability to protect mouse liver slices against ethanol
      induced toxicity and possible mechanism of its protection. Oxidative stress
      markers such as, lipid peroxidation, protein carbonyl formation, amount of 8
      hydroxy-2-deoxyguanosine and antioxidant enzymes levels were measured using
      specific biochemical assays. Poly (ADP-ribose) polymerase (PARP), Bax and Bcl2
      were checked to assess the induction of apoptosis using western blots. The
      results showed that geraniin and amariin protected mouse liver slices against
      ethanol induced cytotoxicity. Both compounds inhibited oxidation of lipid,
      protein and formation of 8-hydroxy-2-deoxyguanosine, all of which were found to
      be elevated on exposure to ethanol. These compounds restored the antioxidant
      enzymes altered on ethanol exposure. Compounds also inhibited the cleavage of
      PARP and bax and restored Bcl2, induced on exposure to ethanol. In summary, both
      ellagitannins effectively protected mouse liver slices against ethanol induced
      cytotoxicity and apoptosis by reducing oxidative damage to biological molecules
      and modulating Bax/Bcl-2 ratio respectively, thus minimizing liver injury.

PMID- 22982333
TI  - Quantum-like model of diauxie in Escherichia coli: operational description of
      precultivation effect.
AB  - In this paper we apply the quantum-like (QL) approach to microbiology to present
      an operational description of the complex process of diauxie in Escherichia coli.
      We take as guaranteed that dynamics in cells is adaptive, i.e., it depends
      crucially on the microbiological context. This very general assumption is
      sufficient to appeal to quantum and more general QL probabilistic models. The
      next step is to find the operational representation - by operators in complex
      Hilbert space (as in quantum physics). To determine QL operators, we used the
      statistical data from Inada et al. (1996). To improve the QL-representation, we
      needed better experimental data. Corresponding experiments were recently done by
      two of the authors and in this paper we use these new data. In these data we
      found that bio-chemical context of precultivation of populations of E. coli plays
      a crucial role in E. coli preferences with respect to sugars. Hence, the form of
      the QL operator representing lactose operon activation also depends crucially on
      precultivation. One of our results is decomposition of the lactose operon
      activation operator to extract the factor determined by precultivation. The QL
      operational approach developed in this paper can be used not only for description
      of the process of diauxie in E. coli, but also other processes of gene
      expression. However, new experimental statistical data are demanded.

PMID- 22982334
TI  - Associations between stress and hearing problems in humans.
AB  - Hearing problems are a public health issue with prevalence figures far more
      common than previously estimated. There are well-established risk factors of
      hearing problems such as age, sex and noise exposure history. Here, we
      demonstrate additional risk factors, i.e. socioeconomic status and long-term
      stress exposure that are found to increase the risk of hearing problems. In order
      to proactively intervene and prevent hearing problems, these newly recognized
      risk factors need to be taken into consideration. When taking these new risk
      factors into account, sex differences become even more apparent than previously
      found. The aim of this review is to summarize our recent findings about the
      associations between stress and hearing problems.

PMID- 22982335
TI  - Molecular and biological characterization of interferon-gamma-inducible-lysosomal
      thiol reductase gene in zebrafish (Danio rerio).
AB  - In mammals, interferon-gamma-inducible-lysosomal thiol reductase (GILT) has been
      demonstrated to play a key role in the processing and presentation of MHC class
      II-restricted antigen (Ag) by catalyzing disulfide bond reduction, thus unfolding
      native protein Ag and facilitating subsequent cleavage by proteases. Here, we
      reported the cloning of a GILT gene homologue from zebrafish (zGILT), a tropical
      freshwater fish. The full-length cDNA of zGILT gene is 768 nucleotides (nt)
      encoding a protein of 255 amino acids (aa), with a putative molecular weight of
      28.33 kDa. The deduced protein is highly homologous to that of fish and mammalian
      GILTs and shares 57.1% sequence identity to that of Atlantic salmon and 55.7
      21.6% sequence identity to that of various mammals. The deduced protein possesses
      all the main features characteristic of known GILT proteins including the
      signature sequence CQHGX2ECX2NX4C spanning residues 117-132, CXXC motif at
      residues 72-75, one potential sites for N-linked glycosylation at residual
      positions 54. The zGILT expression is obviously up-regulated in spleen and kidney
      after immunization with LPS although it also is constitutively expressed in
      heart, liver, muscle and intestine, suggesting that zGILT may be involved in the
      immune response to bacterial challenge. The soluble recombinant protein was
      successfully purified using Ni-nitrilotriacetic acid resin. Recombinant His
      zsGILT appeared on SDS-PAGE in the ranges of their estimated size of 18.94-kDa.
      After purification, further study revealed that zsGILT was capable of catalyzing
      the reduction of the interchain disulfide bonds intact IgG. These results will
      allow for further investigation to unravel the role of this key enzyme in class
      II MHC-restricted antigen processing and to use zebrafish as an in vivo model for
      related studies.

PMID- 22982336
TI  - Two novel short C-type lectin from Chinese mitten crab, Eriocheir sinensis, are
      induced in response to LPS challenged.
AB  - The basic mechanism of host fighting against pathogens is pattern recognition
      receptors recognized pathogen-associated molecular patterns. However, the
      specificity of recognition within the innate immune molecular of invertebrates
      remains largely unknown. For this reason, we investigated the immune
      functionality of two pattern recognition receptors, C-type lectin EsLecA and
      EsLecG, post lipopolysaccharides (LPS) challenge in Chinese mitten crab
      (Eriocheir sinensis), which is a commercially important and disease vulnerable
      aquaculture species. The cloning of full-length EsLecA and EsLecG cDNA were based
      on the initial expressed sequence tags (EST) isolated from a hepatopancreatic
      cDNA library via PCR. The EsLecA cDNA contained a 480-bp open reading frame that
      encoded a putative 159-amino-acid protein, while EsLecG cDNA contained a 465-bp
      open reading frame that encoded a putative 154-amino-acid protein. Comparison,
      with other reported invertebrate and vertebrate sequences, revealed the presence
      of carbohydrate recognition domains that were common among C-type lectin
      superfamilies. EsLecA and EsLecG mRNA expression in E. sinensis were (a) both
      detected in all tissues, including the hepatopancreas, gills, hemocytes, testis,
      accessory gland, ovary, muscle, stomach, intestine, heart, thoracic ganglia and
      brain, and (b) responsive in hepatopancreas, gill, hemocytes post-LPS immuno
      challenge all appeared dramatically variation. Collectively, the data presented
      here demonstrate the successful isolation of two novel C-type lectins from the
      Chinese mitten crab, and their role in the innate immune system of an
      invertebrate.

PMID- 22982337
TI  - Consistent activation of the beta-catenin pathway by Salmonella type-three
      secretion effector protein AvrA in chronically infected intestine.
AB  - Salmonella infection is a common public health problem that can become chronic
      and increase the risk of cancer. Live, mutated Salmonella is used to target
      cancer cells. However, few studies have addressed chronic Salmonella infection in
      vivo. AvrA is a Salmonella type-three secretion effector that is multifunctional,
      inhibiting intestinal inflammation and enhancing proliferation. beta-catenin is a
      key player in intestinal renewal, inflammation, and tumorigenesis. We hypothesize
      that in Salmonella-infected intestine, AvrA chronically activates the beta
      catenin pathway and increases cell proliferation, thus deregulating the
      intestinal responses to bacterial infection. We followed mice with Salmonella
      infection for 27 wk and investigated the physiological effects and role of AvrA
      on beta-catenin in chronically infected intestine. We found that AvrA
      persistently regulated beta-catenin posttranslational modifications, including
      phosphorylation and acetylation. Moreover, the upstream regulator Akt,
      transcription factors, T cell factors, nuclear beta-catenin, and beta-catenin
      target genes were enhanced in mice infected with Salmonella-expressing AvrA. AvrA
      has a chronic functional role in promoting intestinal renewal. In summary, we
      have uncovered an essential role of Salmonella AvrA in chronically activating
      beta-catenin and impacting intestinal renewal in small intestine and colon. Our
      study emphasizes the importance of AvrA in chronic bacterial infection.

PMID- 22982338
TI  - A novel nutrient sensing mechanism underlies substrate-induced regulation of
      monocarboxylate transporter-1.
AB  - Monocarboxylate transporter isoform-1 (MCT1) plays an important role in the
      absorption of short-chain fatty acids (SCFAs) in the colon. Butyrate, a major
      SCFA, serves as the primary energy source for the colonic mucosa, maintains
      epithelial integrity, and ameliorates intestinal inflammation. Previous studies
      have shown substrate (butyrate)-induced upregulation of MCT1 expression and
      function via transcriptional mechanisms. The present studies provide evidence
      that short-term MCT1 regulation by substrates could be mediated via a novel
      nutrient sensing mechanism. Short-term regulation of MCT1 by butyrate was
      examined in vitro in human intestinal C2BBe1 and rat intestinal IEC-6 cells and
      ex vivo in rat intestinal mucosa. Effects of pectin feeding on MCT1, in vivo,
      were determined in rat model. Butyrate treatment (30-120 min) of C2BBe1 cells
      increased MCT1 function {p-(chloromercuri) benzene sulfonate (PCMBS)-sensitive
      [(14)C]butyrate uptake} in a pertussis toxin-sensitive manner. The effects were
      associated with decreased intracellular cAMP levels, increased V(max) of butyrate
      uptake, and GPR109A-dependent increase in apical membrane MCT1 level. Nicotinic
      acid, an agonist for the SCFA receptor GPR109A, also increased MCT1 function and
      decreased intracellular cAMP. Pectin feeding increased apical membrane MCT1
      levels and nicotinate-induced transepithelial butyrate flux in rat colon. Our
      data provide strong evidence for substrate-induced enhancement of MCT1 surface
      expression and function via a novel nutrient sensing mechanism involving GPR109A
      as a SCFA sensor.

PMID- 22982339
TI  - IL-1beta stimulation of CCD-18co myofibroblasts enhances repair of epithelial
      monolayers through Wnt-5a.
AB  - Subepithelial myofibroblasts are involved in the initiation and coordination of
      intestinal epithelial repair, but the molecular signaling pathways are largely
      unknown. The cellular adaptations that occur during repair range from
      dedifferentiation and migration to proliferation and redifferentiation, in a way
      that is strongly reminiscent of normal crypt-to-villus epithelial maturation. We
      therefore hypothesized that Wnt/beta-catenin signaling may have a pivotal role in
      intestinal epithelial wound repair. We used the established scratch wound method
      in Caco-2 cells and in nontransformed NCM460 cells to monitor the effects of IL
      1beta-stimulated colonic myofibroblasts (CCD-18co) on intestinal epithelial
      repair, with immunoblotting and immunodepletion to examine the conditioned media.
      Conditioned media from IL-1beta-stimulated, but not -untreated, myofibroblasts
      increased Caco-2 wound closure twofold over 24 h. IL-1beta-stimulated
      myofibroblasts downregulated the differentiation marker sucrase-isomaltase in the
      Caco-2 cells, whereas the proliferation marker c-myc was upregulated. Array
      expression profiling identified Wnt-5a as the Wnt-related gene that was most
      upregulated (28-fold) by IL-1beta stimulation of CCDs. Recombinant Wnt-5a
      enhanced proliferation of Caco-2 and NCM460 cells. In scratch assays, it
      increased migration of the leading edge in both cell lines. Wnt-5a
      immunodepletion of the IL-1beta-CCD conditioned media abrogated the ability to
      enhance the repair. Wnt-5a often acts through a noncanonical signal transduction
      pathway. Further experiments supported this pathway in epithelial wound healing:
      IL-1beta-CCD-mediated repair was not affected by the addition of the canonical
      Wnt antagonist Dickkopf-1. Furthermore, media from stimulated myofibroblasts (but
      not Wnt-5a-depleted media) increased c-jun in Caco-2 cell nuclear extracts.
      Myofibroblast-mediated noncanonical Wnt-5a signaling is therefore important in
      the dedifferentiation and migration stages of epithelial wound repair.

PMID- 22982340
TI  - Inflammation and symptoms of depression and anxiety in patients with acute
      coronary heart disease.
AB  - Depression following an acute coronary syndrome (ACS, including myocardial
      infarction or unstable angina) is associated with recurrent cardiovascular
      events, but the depressive symptoms that are cardiotoxic appear to have
      particular characteristics: they are 'incident' rather than being a continuation
      of prior depression, and they are somatic rather than cognitive in nature. We
      tested the hypothesis that the magnitude of inflammatory responses during the ACS
      would predict somatic symptoms of depression 3 weeks and 6 months later,
      specifically in patients without a history of depressive illness. White cell
      count and C-reactive protein were measured on the day after admission in 216 ACS
      patients. ACS was associated with very high levels of inflammation, averaging
      13.23*10(9)/l and 17.06 mg/l for white cell count and C-reactive protein
      respectively. White cell count during ACS predicted somatic symptom intensity on
      the Beck Depression Inventory 3 weeks later (beta=0.122, 95% C.I. 0.015-0.230,
      p=0.025) independently of age, sex, ethnicity, socioeconomic status, marital
      status, smoking, cardiac arrest during admission and clinical cardiac risk, but
      only in patients without a history of depression. At 6 months, white cell count
      during ACS was associated with elevated anxiety on the Hospital Anxiety and
      Depression Scale independently of covariates including anxiety measured at 3
      weeks (adjusted odds ratio 1.08, 95% C.I. 1.01-1.15, p=0.022). An unpredicted
      relationship between white cell count during ACS and cognitive symptoms of
      depression at 6 months was also observed. The study provides some support for the
      hypothesis that the marked inflammation during ACS contributes to later
      depression in a subset of patients, but the evidence is not conclusive.

PMID- 22982341
TI  - Postnatal administration of IL-1Ra exerts neuroprotective effects following
      perinatal inflammation and/or hypoxic-ischemic injuries.
AB  - New therapeutic strategies are needed to protect neonates, especially premature
      newborns, against brain injury and associated neurobehavioral deficits. The role
      of pro-inflammatory cytokines, especially IL-1beta, in the pathophysiological
      pathway leading to neonatal brain damage is increasingly recognized and
      represents an attractive therapeutic target. We investigated the therapeutic
      potential of postnatal systemic administration of the interleukin (IL)-1 receptor
      antagonist (IL-1Ra) in an animal model of perinatal brain injury using the
      insults most common to human neonates, i.e. prenatal exposure to inflammation
      and/or postnatal hypoxia-ischaemia (HI). We found that postnatal administration
      of IL-1Ra preserved motor function and exploratory behavior after either prenatal
      exposure to inflammatory agent lipopolysaccharide (LPS) or postnatal HI insult.
      The deleterious effect of combined prenatal LPS and postnatal HI on brain
      development was also alleviated by administration of IL-1Ra, as seen by the
      protected neural stem cell population, prevention of myelin loss in the internal
      capsule, decreased gliosis, and decreased neurobehavioral impairment. This study
      showed the distinct pattern of functional deficits induced by prenatal
      inflammation as compared to postnatal HI and the therapeutic potential of IL-1Ra
      administration against neonatal brain injury. Furthermore, our results highlight
      the potential for postnatal treatment of prenatal inflammatory stressors.

PMID- 22982342
TI  - Identifying and collecting pertinent medical records for centralized abstraction
      in a multi-center randomized clinical trial: the model used by the American
      College of Radiology arm of the National Lung Screening Trial.
AB  - BACKGROUND: In clinical trials and epidemiologic studies, information on medical
      care utilization and health outcomes is often obtained from medical records. For
      multi-center studies, this information may be gathered by personnel at individual
      sites or by staff at a central coordinating center. We describe the process used
      to develop a HIPAA-compliant centralized process to collect medical record
      information for a large multi-center cancer screening trial. METHODS: The
      framework used to select, request, and track medical records incorporated a
      participant questionnaire with unique identifiers for each medical provider. De
      identified information from the questionnaires was sent to the coordinating
      center indexed by these identifiers. The central coordinating center selected
      specific medical providers for abstraction and notified sites using these
      identifiers. The site personnel then linked the identifiers with medical provider
      information. Staff at the sites collected medical records and provided them for
      central abstraction. RESULTS: Medical records were successfully obtained and
      abstracted to ascertain information on outcomes and health care utilization in a
      study with over 18,000 study participants. Collection of records required for
      outcomes related to positive screening examinations and lung cancer diagnosis
      exceeded 90%. Collection of records for all aims was 87.32%. CONCLUSIONS: We
      designed a successful centralized medical record abstraction process that may be
      generalized to other research settings, including observational studies. The
      coordinating center received no identifying data. The process satisfied
      requirements imposed by the Health Insurance Portability and Accountability Act
      and concerns of site institutional review boards with respect to protected health
      information.

PMID- 22982343
TI  - Opto-fMRI analysis for exploring the neuronal connectivity of the hippocampal
      formation in rats.
AB  - In recent years, optical stimulation of neurons that bear a light-gated cation
      channel, "Optogenetics", has opened a new avenue for exploring neuronal
      connectivity of the nervous system. In this study, we applied a technique, "Opto
      fMRI", which combined optogenetics with blood oxygenation level-dependent (BOLD)
      functional MRI (fMRI), for examining the neuronal connectivity of the hippocampal
      formation in rats. Although the hippocampal formation is very important for
      memory formation and retrieval, there is little information on its neuronal
      connectivity, especially on its longitudinal axis of connection. For this
      purpose, we utilized a transgenic rat strain, expressing the light-gated cation
      channel channelrhodopsin-2 (ChR2) under the regulation of the Thy1.2 promoter
      which permits the expression of the integrated gene in neurons. After optical
      stimulation targeting the dentate gyrus of the transgenic rat, we detected BOLD
      response of not only the dentate gyrus (DG) but also at the CA3 area. In
      addition, we detected the longitudinal-axis activation of the hippocampus after
      optical stimulation. Our study suggests that Opto-fMRI could be a tool for
      exploring the neuronal connectivity of the hippocampal formation, to understand
      the neural basis of memory formation and retrieval.

PMID- 22982344
TI  - Structural and biochemical alterations during the healing process of tendons
      treated with Aloe vera.
AB  - AIMS: The tendon is composed of highly organized collagen fibers that form a
      complex supramolecular structure. After lesions, the organization and composition
      of the tendon are not completely restored. Our purpose was to evaluate if the
      application of Aloe vera improves tendon healing, considering the effectiveness
      in the stimulus of collagen synthesis. MAIN METHODS: The calcaneal tendon of male
      Wistar rats was partially transected with subsequent topical application of A.
      vera ointment at the injury. The animals were separated into groups with tendons
      treated with the A. vera extract for 7days and excised on the 7th, 14th and 21st
      days after surgery; control rats received only ointment base without plant
      extract. KEY FINDINGS: Morphological analysis using polarization microscopy
      showed that the entire tendon undergoes a remodeling process, with disorganized
      collagen fibers by days 7 and 14 in plant-treated and non-treated groups and with
      a higher birefringence in tendons of the plant-treated group on the 21st day. A
      higher concentration of hydroxyproline was found in plant-treated tendons on days
      7 and 14 compared with their controls. Western blots showed lower amounts of type
      I collagen in the plant-treated group on day 14 compared with the control. MMP-9
      diminished 14days after lesion and the active isoform of MMP-2 increased on day
      21 in plant-treated groups. SIGNIFICANCE: The present study indicates a
      beneficial effect of A. vera in the tissue reorganization in the transected
      region of the tendon 21days after injury and is supported by an increase of
      active MMP-2.

PMID- 22982345
TI  - Cardioprotection from remote preconditioning involves spinal opioid receptor
      activation.
AB  - AIMS: Remote preconditioning is a powerful and potentially clinically viable mode
      of cardioprotection. The mechanisms underlying its transmission process have not
      been extensively studied. The aim of this study was to test the hypothesis that
      spinal opioid receptors are involved with signal transmission of remote cardiac
      preconditioning. MAIN METHODS: Two established models of remote preconditioning
      were used, one using intermittent ischaemia of the lower limb (remote ischaemic
      preconditioning, RIPC) and the other by stimulation of cutaneous pain fibres via
      an abdominal incision (remote preconditioning of trauma, RPOT). Classic ischaemic
      preconditioning (IPC) was used as positive control. Selective blockade of spinal
      opioid receptors was achieved through intrathecal injection of naloxone
      methiodide, a compound not known to cross the blood-brain barrier. KEY FINDINGS:
      The prior introduction of naloxone methiodide abolished the cardioprotective
      effects of RIPC, RPOT but not IPC, as assessed by infarct size as a percentage of
      area at risk following 30min of ischaemia and 120min reperfusion. Of the specific
      receptor antagonists, only that specific for the mu receptor subtype, and not
      delta or kappa receptor, block the protective response. SIGNIFICANCE: These
      results suggest that the central nervous system at the spinal cord level is
      involved with the relaying of signals between the afferent and efferent arms of
      remote preconditioning.

PMID- 22982346
TI  - Regeneration in heart disease-Is ECM the key?
AB  - The heart possesses a regeneration potential derived from endogenous and
      exogenous stem and progenitor cell populations, though baseline regeneration
      appears to be sub-therapeutic. This limitation was initially attributed to a lack
      of cells with cardiomyogenic potential following an insult to the myocardium.
      Rather, recent studies demonstrate increased numbers of cardiomyocyte progenitor
      cells in diseased hearts. Given that the limiting factor does not appear to be
      cell quantity but rather repletion of functional cardiomyocytes, it is crucial to
      understand potential mechanisms inhibiting progenitor cell differentiation. One
      of the extensively studied areas in heart disease is extracellular matrix (ECM)
      remodeling, with both the composition and mechanical properties of the ECM
      undergoing changes in diseased hearts. This review explores the influence of ECM
      properties on cardiomyogenesis and adult cardiac progenitor cells.

PMID- 22982347
TI  - Oxygen delivery during extreme anemia with ultra-pure earthworm hemoglobin.
AB  - AIM: Lumbricus terrestris (earthworm) erythrocruorin (LtEc) is a naturally
      occurring extracellular hemoglobin (Hb) with high molecular weight (3.6MDa), low
      autoxidation rate, and limited nitric oxide (NO) dioxygenation activity. These
      properties make LtEc a potential candidate for use as red blood cell (RBC)
      substitute, i.e. Hb-based oxygen carrier (HBOC). Previous studies have shown that
      small amounts of LtEc can be safely transfused into mice, rats, and hamsters
      without eliciting major side effects. Therefore, this study was designed to
      understand oxygen (O(2)) transport to tissues and systemic/microvascular
      hemodynamics induced by LtEc during anemic conditions. MAIN METHODS: Hamsters
      fitted with dorsal window chambers were hemodiluted to 18% hematocrit (Hct) using
      6g/dL dextran 70kDa (Dex70). Hemodilution was then continued to 11% Hct using
      10g/dL LtEc, 6g/dL Dex70 or 10g/dL human serum albumin (HSA). Blood pressure,
      heart rate, blood gas parameters, microvascular hemodynamics, microvascular blood
      flow, functional capillary density (FCD), intravascular pO(2) and perivascular
      pO(2) were studied. KEY FINDINGS: LtEc maintained blood pressure without inducing
      vasoconstriction while increasing microvascular perfusion and FCD relative to
      Dex70 and HSA. LtEc increased blood O(2) carrying capacity and maintained
      systemic and microvascular parameters without decreasing arteriolar diameter or
      increasing vascular resistance with during extreme anemia. LtEc increased O(2)
      delivery compared to conventional plasma expanders. SIGNIFICANCE: LtEc or
      synthetic molecules that replicate the characteristics of LtEc could be effective
      O(2) carriers with potential to be used in transfusion medicine to prevent tissue
      anoxia resulting from severe anemia.

PMID- 22982348
TI  - Ingestion of cocoa ameliorates endothelial dysfunction in mesentery arterioles
      induced by high fat diet in rats: an in vivo intravital microscopy study.
AB  - AIMS: Numerous clinical studies have reported that ingestion of cocoa has a
      therapeutic effect on hypertension. However, there is only limited information on
      the mechanism of ingestion of cocoa on arterioles, vessels that have a major role
      in determining blood pressure. In this study, we used intravital video-microscopy
      to evaluate the effect of cocoa consumption on the mesentery microcirculation of
      rats fed a high fat diet. MAIN METHODS: The animals were allocated to 3 groups,
      and fed either a control diet, a high fat diet containing 15% lard, or the HFD
      with 2% cocoa (HFD-C) for 6 weeks. At the end of the experimental period, the
      mesentery was spread in a chamber, and the vessels were treated topically with
      phenylephrine, acetylcholine, or papaverine. The vascular responses to
      phenylephrine, acetylcholine-dependent vasodilatation and endothelium-independent
      vasodilatation were calculated by the diameter of the mesentery artery with each
      treatment. KEY FINDINGS: Topical treatment of mesenteric arterioles with
      acetylcholine caused a significantly greater response in the control compared
      with the HFD group. In the HFD-C group, acetylcholine-dependent vasodilatation
      was decreased marginally. Similarly, rats in the HFD group showed a significant
      reduction in vascular sensitivity to phenylephrine compared with the control
      group. However, there was no significant difference between the control and HFD-C
      groups. The induction of endothelial-independent artery dilation was reduced
      slightly in the HFD group. SIGNIFICANCE: Our results suggest that one of the
      hypotensive mechanisms of cocoa is due to amelioration of endothelial dysfunction
      in arterioles induced by an inappropriate diet.

PMID- 22982349
TI  - Protective effects of alpha-pinene in mice with cerulein-induced acute
      pancreatitis.
AB  - AIMS: Acute pancreatitis (AP) is a complicated inflammatory disease that has an
      unknown underlying pathogenesis. Because alpha-pinene can modulate inflammation,
      we examined whether alpha-pinene plays a role in AP. MAIN METHODS: Alpha-pinene
      was administered intraperitoneally 1h prior to the first injection of cerulein.
      Once AP developed, cerulein, a stable cholecystokinin analog, was injected hourly
      over a 6-h period. Blood samples were taken 6h later to determine serum amylase
      and lipase levels. The pancreas and lungs were rapidly removed for morphological
      examination, myeloperoxidase assay, and real-time reverse transcription
      polymerase chain reaction. We also isolated the pancreatic acinar cells using a
      collagenase solution. Cell viability, and cytokine productions were measured in
      pancreatic acini. KEY FINDINGS: Intraperitoneal administration of alpha-pinene
      reduced the pancreatic weight (PW) to body weight (BW) ratio and the serum levels
      of amylase and lipase. Alpha-pinene treatment also reduced histological damage
      and myeloperoxidase activity in the pancreas and lungs. Furthermore, alpha-pinene
      pretreatment reduced the production of pancreatic tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, and IL-6 during cerulein-induced AP. In vitro,
      alpha-pinene inhibited cerulein-induced cell death and cytokine production in
      isolated cerulein-treated pancreatic acinar cells. SIGNIFICANCE: These findings
      suggest that alpha-pinene has an anti-inflammatory effect during cerulein-induced
      AP.

PMID- 22982351
TI  - Advanced scanning transmission stereo electron microscopy of structural and
      functional engineering materials.
AB  - Stereo transmission electron microscopy (TEM) provides a 3D impression of the
      microstructure in a thin TEM foil. It allows to perform depth and TEM foil
      thickness measurements and to decide whether a microstructural feature lies
      inside of a thin foil or on its surface. It allows appreciating the true three
      dimensional nature of dislocation configurations. In the present study we first
      review some basic elements of classical stereo TEM. We then show how the method
      can be extended by working in the scanning transmission electron microscope
      (STEM) mode of a modern analytical 200 kV TEM equipped with a field emission gun
      (FEG TEM) and a high angle annular dark field (HAADF) detector. We combine two
      micrographs of a stereo pair into one anaglyph. When viewed with special colored
      glasses the anaglyph provides a direct and realistic 3D impression of the
      microstructure. Three examples are provided which demonstrate the potential of
      this extended stereo TEM technique: a single crystal Ni-base superalloy, a 9%
      Chromium tempered martensite ferritic steel and a NiTi shape memory alloy. We
      consider the effect of camera length, show how foil thicknesses can be measured,
      and discuss the depth of focus and surface effects.

PMID- 22982350
TI  - Resveratrol attenuates oxidative damage and ameliorates cognitive impairment in
      the brain of senescence-accelerated mice.
AB  - AIMS: Resveratrol (Res) which is a polyphenolic phytoalexin, has various
      biological properties. In the present study, we investigated whether Res
      extracted from Polygonum cuspidatum can reduce oxidative damage and cognitive
      impairment in senescence-accelerated mouse (SAM). MAIN METHODS: Senescence
      accelerated mice were administered with Res (25, 50, 100mg.kg(-1).d(-1)) for
      8weeks. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px) and the content of malondialdehyde (MDA) in mice brain were determined. The
      gene expression of SOD in mice brain was investigated by real time reverse
      transcriptase-polymerase chain reaction (RT-PCR). KEY FINDINGS: The results
      showed that resveratrol significantly improved learning and memory ability in
      Morris water maze test and neuromuscular coordination and sensorimotor capacity
      in tightrope test. Meanwhile, Res increased the activities of antioxidant enzymes
      with a reduction in lipid peroxidation. And real time RT-PCR analysis also
      indicated that the change of SOD mRNA was the same as the modification of SOD
      activity in mice brain. Furthermore, Res could prevent cerebral mitochondrial DNA
      deletions which might be one of the causes resulting in learning and memory
      impairment. SIGNIFICANCE: These results suggest that the pharmacological action
      of Res may offer a novel therapeutic strategy for the treatment of age-related
      conditions.

PMID- 22982352
TI  - Structural basis of transcription elongation.
AB  - For transcription elongation, all cellular RNA polymerases form a stable
      elongation complex (EC) with the DNA template and the RNA transcript. Since the
      millennium, a wealth of structural information and complementary functional
      studies provided a detailed three-dimensional picture of the EC and many of its
      functional states. Here we summarize these studies that elucidated EC structure
      and maintenance, nucleotide selection and addition, translocation, elongation
      inhibition, pausing and proofreading, backtracking, arrest and reactivation,
      processivity, DNA lesion-induced stalling, lesion bypass, and transcriptional
      mutagenesis. In the future, additional structural and functional studies of
      elongation factors that control the EC and their possible allosteric modes of
      action should result in a more complete understanding of the dynamic molecular
      mechanisms underlying transcription elongation. This article is part of a Special
      Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22982353
TI  - Increased impact of a contraceptive vaginal ring with ethinyl estradiol and
      nestorone on C-reactive protein.
AB  - OBJECTIVE & STUDY DESIGN: In a parallel design, 23 and 22 healthy pre-menopausal
      women were randomly administered a contraceptive vaginal ring (CVR) delivering
      150/15 MUg Nestorone(r)/ethinyl estradiol (EE) daily or an oral contraceptive
      (OC) containing levonorgestrel and EE (150/30 MUg) for three cycles, to compare
      the effects on C-reactive protein and other markers of inflammation. ANCOVA was
      performed with baseline values as covariate. RESULTS: The CVR caused [estimate of
      difference (95% CI), 109% (16-275%)] higher levels of CRP than the OC, while no
      difference was observed for leukocyte 1% (-13/+17%) and monocyte counts 6% (
      9/+23%). The greater increase in CRP was confined to CVR recipients exhibiting
      low pre-treatment CRP-levels, whereas no difference was observed in the increases
      for recipients in the highest tertile of pre-treatment CRP levels. CONCLUSION:
      The difference in CRP rise in CVR and OC users does not correspond with the
      effects on other markers of inflammation and is most likely due to a specific
      difference in the effect of ethinyl-estradiol combined with nestorone in cases
      with low CRP.

PMID- 22982354
TI  - No association between striatal dopamine transporter binding and body mass index:
      a multi-center European study in healthy volunteers.
AB  - INTRODUCTION: Dopamine is one among several neurotransmitters that regulate food
      intake and overeating. Thus, it has been linked to the pathophysiology of obesity
      and high body mass index (BMI). Striatal dopamine D(2) receptor availability is
      lower in obesity and there are indications that striatal dopamine transporter
      (DAT) availability is also decreased. In this study, we tested whether BMI and
      striatal DAT availability are associated. METHODS: The study included 123 healthy
      individuals from a large European multi-center database. They had a BMI range of
      18.2-41.1 kg/m(2) and were scanned using [(123)I]FP-CIT SPECT imaging. Scans were
      analyzed with both region-of-interest and voxel-based analysis to determine the
      binding potential for DAT availability in the caudate nucleus and putamen. A
      direct relation between BMI and DAT availability was assessed and groups with
      high and low BMI were compared for DAT availability. RESULTS: No association
      between BMI and striatal DAT availability was found. CONCLUSION: The lack of an
      association between BMI and striatal DAT availability suggests that the
      regulation of striatal synaptic dopamine levels by DAT plays no or a limited role
      in the pathophysiology of overweight and obesity.

PMID- 22982355
TI  - Reinforcement learning signals in the anterior cingulate cortex code for others'
      false beliefs.
AB  - The ability to recognise that another's belief is false is a hallmark of our
      capacity to understand others' mental states. It has been suggested that the
      computational and neural mechanisms that underpin learning about others' mental
      states may be similar to those that underpin first-person Reinforcement Learning
      (RL). In RL, unexpected decision-making outcomes constitute prediction errors
      (PE), which are coded for by neurons in the Anterior Cingulate Cortex (ACC). Does
      the ACC signal the PEs (false beliefs) of others about the outcomes of their
      decisions? We scanned subjects using fMRI while they monitored a third-person's
      decisions and similar responses made by a computer. The outcomes of the trials
      were manipulated, such that the actual outcome was unexpectedly different from
      the predicted outcome on 1/3 of trials. We examined activity time-locked to
      privileged information which indicated the actual outcomes only to subjects.
      Activity in the gyral ACC was found when the outcomes of the third-person's
      decisions were unexpectedly positive. Activity in the sulcal ACC was found when
      the third-person's or computer's outcomes were unexpectedly positive. We suggest
      that a property of the ACC is that it codes PEs, with a portion of the gyral ACC
      specialised for processing the PEs of others.

PMID- 22982356
TI  - Dissociation between process-based and data-based limitations for conscious
      perception in the human brain.
AB  - Successful performance of a cognitive task depends upon both the quality of the
      sensory information and the processing resources available to perform that task.
      Thus, task performance can either be data-limited or process-limited (D. A.
      Norman and D. G. Bobrow, 1975). Using fMRI, we show that these conceptual
      distinctions are neurally dissociable: A parieto-frontal network involved in
      conscious perception is modulated by target interference manipulations that
      strain attentional processing, but not by equally difficult manipulations that
      limit the quality of target information. These results suggest that limitations
      imposed by processing capacity have distinct neural effects from those arising
      from the quality of sensory input, and provide empirical support for an
      influential neurobiological theory of consciousness (S. Dehaene, J.-P. Changeux,
      L. Naccache, J. Sackur, and C. Sergent, 2006).

PMID- 22982358
TI  - Binary classification of 18F-flutemetamol PET using machine learning: comparison
      with visual reads and structural MRI.
AB  - (18)F-flutemetamol is a positron emission tomography (PET) tracer for in vivo
      amyloid imaging. The ability to classify amyloid scans in a binary manner as
      'normal' versus 'Alzheimer-like', is of high clinical relevance. We evaluated
      whether a supervised machine learning technique, support vector machines (SVM),
      can replicate the assignments made by visual readers blind to the clinical
      diagnosis, which image components have highest diagnostic value according to SVM
      and how (18)F-flutemetamol-based classification using SVM relates to structural
      MRI-based classification using SVM within the same subjects. By means of SVM with
      a linear kernel, we analyzed (18)F-flutemetamol scans and volumetric MRI scans
      from 72 cases from the (18)F-flutemetamol phase 2 study (27 clinically probable
      Alzheimer's disease (AD), 20 amnestic mild cognitive impairment (MCI), 25
      controls). In a leave-one-out approach, we trained the (18)F-flutemetamol based
      classifier by means of the visual reads and tested whether the classifier was
      able to reproduce the assignment based on visual reads and which voxels had the
      highest feature weights. The (18)F-flutemetamol based classifier was able to
      replicate the assignments obtained by visual reads with 100% accuracy. The voxels
      with highest feature weights were in the striatum, precuneus, cingulate and
      middle frontal gyrus. Second, to determine concordance between the gray matter
      volume- and the (18)F-flutemetamol-based classification, we trained the
      classifier with the clinical diagnosis as gold standard. Overall sensitivity of
      the (18)F-flutemetamol- and the gray matter volume-based classifiers were
      identical (85.2%), albeit with discordant classification in three cases.
      Specificity of the (18)F-flutemetamol based classifier was 92% compared to 68%
      for MRI. In the MCI group, the (18)F-flutemetamol based classifier distinguished
      more reliably between converters and non-converters than the gray matter-based
      classifier. The visual read-based binary classification of (18)F-flutemetamol
      scans can be replicated using SVM. In this sample the specificity of (18)F
      flutemetamol based SVM for distinguishing AD from controls is higher than that of
      gray matter volume-based SVM.

PMID- 22982357
TI  - Development of brain structural connectivity between ages 12 and 30: a 4-Tesla
      diffusion imaging study in 439 adolescents and adults.
AB  - Understanding how the brain matures in healthy individuals is critical for
      evaluating deviations from normal development in psychiatric and
      neurodevelopmental disorders. The brain's anatomical networks are profoundly re
      modeled between childhood and adulthood, and diffusion tractography offers
      unprecedented power to reconstruct these networks and neural pathways in vivo.
      Here we tracked changes in structural connectivity and network efficiency in 439
      right-handed individuals aged 12 to 30 (211 female/126 male adults, mean
      age=23.6, SD=2.19; 31 female/24 male 12 year olds, mean age=12.3, SD=0.18; and 25
      female/22 male 16 year olds, mean age=16.2, SD=0.37). All participants were
      scanned with high angular resolution diffusion imaging (HARDI) at 4 T. After we
      performed whole brain tractography, 70 cortical gyral-based regions of interest
      were extracted from each participant's co-registered anatomical scans. The
      proportion of fiber connections between all pairs of cortical regions, or nodes,
      was found to create symmetric fiber density matrices, reflecting the structural
      brain network. From those 70 * 70 matrices we computed graph theory metrics
      characterizing structural connectivity. Several key global and nodal metrics
      changed across development, showing increased network integration, with some
      connections pruned and others strengthened. The increases and decreases in fiber
      density, however, were not distributed proportionally across the brain. The
      frontal cortex had a disproportionate number of decreases in fiber density while
      the temporal cortex had a disproportionate number of increases in fiber density.
      This large-scale analysis of the developing structural connectome offers a
      foundation to develop statistical criteria for aberrant brain connectivity as the
      human brain matures.

PMID- 22982359
TI  - Convolution models for induced electromagnetic responses.
AB  - In Kilner et al. [Kilner, J.M., Kiebel, S.J., Friston, K.J., 2005. Applications
      of random field theory to electrophysiology. Neurosci. Lett. 374, 174-178.] we
      described a fairly general analysis of induced responses-in electromagnetic brain
      signals-using the summary statistic approach and statistical parametric mapping.
      This involves localising induced responses-in peristimulus time and frequency-by
      testing for effects in time-frequency images that summarise the response of each
      subject to each trial type. Conventionally, these time-frequency summaries are
      estimated using post-hoc averaging of epoched data. However, post-hoc averaging
      of this sort fails when the induced responses overlap or when there are multiple
      response components that have variable timing within each trial (for example
      stimulus and response components associated with different reaction times). In
      these situations, it is advantageous to estimate response components using a
      convolution model of the sort that is standard in the analysis of fMRI time
      series. In this paper, we describe one such approach, based upon ordinary least
      squares deconvolution of induced responses to input functions encoding the onset
      of different components within each trial. There are a number of fundamental
      advantages to this approach: for example; (i) one can disambiguate induced
      responses to stimulus onsets and variably timed responses; (ii) one can test for
      the modulation of induced responses-over peristimulus time and frequency-by
      parametric experimental factors and (iii) one can gracefully handle confounds
      such as slow drifts in power-by including them in the model. In what follows, we
      consider optimal forms for convolution models of induced responses, in terms of
      impulse response basis function sets and illustrate the utility of deconvolution
      estimators using simulated and real MEG data.

PMID- 22982360
TI  - Quantitative MRI in the very preterm brain: assessing tissue organization and
      myelination using magnetization transfer, diffusion tensor and T1 imaging.
AB  - Magnetization transfer ratio (MTR), diffusion tensor imaging (DTI) parameters and
      T(1) relaxometry values were used to create parametric maps characterizing the
      tissue microstructure of the neonatal brain in infants born very premature (24-32
      gestational weeks) and scanned at preterm and term equivalent age. Group-wise
      image registration was used to determine anatomical correspondence between
      individual scans and the pooled parametric data at the preterm and term ages.
      These parametric maps showed distinct contrasts whose interrelations varied
      across brain regions and between the preterm and term period. Discrete patterns
      of regional variation were observed for the different quantitative parameters,
      providing evidence that MRI is sensitive to multiple independent aspects of brain
      maturation. MTR values showed a marked change in the pattern of regional
      variation at term equivalent age compared to the preterm period such that the
      ordinal ranking of regions by signal contrast changed. This was unlike all other
      parameters where the regional ranking was preserved at the two time points.
      Interpreting the data in terms of myelination and structural organization, we
      report on the concordance with available histological data and demonstrate the
      value of quantitative MRI for tracking brain maturation over the neonatal period.

PMID- 22982361
TI  - WITHDRAWN: Simple-statistical and composite-statistical scrutinizers to optimize
      metabolome coverage.
AB  - This article has been withdrawn at the request of the author 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- 22982362
TI  - An ion-current-based, comprehensive and reproducible proteomic strategy for
      comparative characterization of the cellular responses to novel anti-cancer
      agents in a prostate cell model.
AB  - Proteome-level investigation of the molecular targets in anticancer action of
      promising pharmaceutical candidates is highly desirable but remains challenging
      due to the insufficient proteome coverage, limited capacity for biological
      replicates, and largely unregulated false positive biomarker discovery of current
      methods. This study described a practical platform strategy to address these
      challenges, using comparison of drug response proteomic signatures by two
      promising anti-cancer agents (KX01/KX02) as the model system for method
      development/optimization. Drug-treated samples were efficiently extracted
      followed by precipitation/on-pellet-digestion procedure that provides high,
      reproducible peptide recovery. High-resolution separations were performed on a 75
      cm-long, heated nano-LC column with a 7-h gradient, with a highly reproducible
      nano-LC/nanospray configuration. An LTQ Orbitrap hybrid mass spectrometer with a
      charge overfilling approach to enhance sensitivity was used for detection.
      Analytical procedures were optimized and well-controlled to achieve high run-to
      run reproducibility that permits numerous replicates in one set, and an ion
      current-based approach was utilized for quantification. The false positives of
      biomarker discovery arising from technical variability was controlled based on
      FBDR measurement by comparing biomarker numbers in each drug-treated group vs.
      "sham samples", which were analyzed in an order randomly interleaved with the
      analysis drug-treated samples. More than 1500 unique protein groups were
      quantified under stringent criteria, and of which about 30% displayed
      differential expression with FBDR of 0.3-2.1% across groups. Comparison of drug
      response proteomic signatures and the subsequent immunoassay revealed that the
      action mechanisms of KX01/KX02 are similar but significantly different from
      vinblastine, which correlates well with clinical and pre-clinical observations.
      Furthermore, the results strongly supported the hypothesis that KX01/KX02 are
      dual-action agents (through inhibition of tubulin and Src). Moreover, informative
      insights into the drug-actions on cell cycle, growth/proliferation, and apoptosis
      were obtained. This platform technology provides extensive evaluation of drug
      candidates and facilitates in-depth mechanism studies.

PMID- 22982363
TI  - Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription.
AB  - The eukaryotic RNA polymerase II (RNAPII) catalyzes the transcription of all
      protein encoding genes and is also responsible for the generation of small
      regulatory RNAs. RNAPII has evolved a unique domain composed of heptapeptide
      repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the C
      terminus (CTD) of its largest subunit (Rpb1). Dynamic phosphorylation patterns of
      serine residues in CTD during gene transcription coordinate the recruitment of
      factors to the elongating RNAPII and to the nascent transcript. Recent studies
      identified threonine 4 and tyrosine 1 as new CTD modifications and thereby
      expanded the "CTD code". In this review, we focus on CTD phosphorylation and its
      function in the RNAPII transcription cycle. We also discuss in detail the
      limitations of the phosphospecific CTD antibodies, which are used in all studies.
      This article is part of a Special Issue entitled: RNA Polymerase II Transcript
      Elongation.

PMID- 22982364
TI  - Promoter clearance by RNA polymerase II.
AB  - Many changes must occur to the RNA polymerase II (pol II) transcription complex
      as it makes the transition from initiation into transcript elongation. During
      this intermediate phase of transcription, contact with initiation factors is lost
      and stable association with the nascent transcript is established. These changes
      collectively comprise promoter clearance. Once the transcript elongation complex
      has reached a point where its properties are indistinguishable from those of
      complexes with much longer transcripts, promoter clearance is complete. The
      clearance process for pol II consists of a number of steps and it extends for a
      surprisingly long distance downstream of transcription start. This article is
      part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

PMID- 22982366
TI  - Propionic acid production in a plant fibrous-bed bioreactor with immobilized
      Propionibacterium freudenreichii CCTCC M207015.
AB  - A plant fibrous-bed bioreactor (PFB) was constructed for propionic acid
      production. Sugar cane bagasse was applied to the PFB as immobilizing material.
      Starting at a concentration of 80g/L of glucose, Propionibacterium freudenreichii
      CCTCC M207015 produced 41.20+/-2.03g/L of propionic acid at 108h in the PFB. The
      value was 21.07% higher than that produced by free cell fermentation.
      Intermittent and constant fed-batch fermentations were performed in the PFB to
      optimize the fermentation results. The highest propionic acid concentration
      obtained from constant fed-batch fermentation was 136.23+/-6.77g/L, which is 1.40
      times higher than the highest concentration (97.00g/L) previously reported.
      Scanning electron microscopy analysis showed that cells exhibited striking
      changes in morphology after PFB domestication. Compared with free cell
      fermentation, the fluxes of propionic acid synthesis and the pentose phosphate
      pathway in PFB fermentation increased by 84.65% and 227.62%, respectively. On the
      other hand, a decrease in succinic and acetic acid fluxes was also observed. The
      metabolic flux distributions of the two PFB fed-batch fermentation strategies
      also demonstrated that constant fed-batch fermentation is a more beneficial
      method for the immobilized production of propionic acid. The relevant key enzyme
      activities and metabolic flux variations of the batch cultures showed good
      consistency. These results suggest that the PFB was effective in high
      concentration propionic acid production.

PMID- 22982365
TI  - Basic mechanism of transcription by RNA polymerase II.
AB  - RNA polymerase II-like enzymes carry out transcription of genomes in Eukaryota,
      Archaea, and some viruses. They also exhibit fundamental similarity to RNA
      polymerases from bacteria, chloroplasts, and mitochondria. In this review we take
      an inventory of recent studies illuminating different steps of basic
      transcription mechanism, likely common for most multi-subunit RNA polymerases.
      Through the amalgamation of structural and computational chemistry data we
      attempt to highlight the most feasible reaction pathway for the two-metal
      nucleotidyl transfer mechanism, and to evaluate the way catalysis can be linked
      to translocation in the mechano-chemical cycle catalyzed by RNA polymerase II.
      This article is part of a Special Issue entitled: RNA polymerase II Transcript
      Elongation.

PMID- 22982367
TI  - Ameliorative effect of yokukansan on vacuous chewing movement in haloperidol
      induced rat tardive dyskinesia model and involvement of glutamatergic system.
AB  - Effects of yokukansan (YKS) on vacuous chewing movement (VCM), which is an index
      for tardive dyskinesia, were investigated in haloperidol decanoate-treated rats.
      Haloperidol decanoate was injected to a thigh muscle once every four weeks for 18
      weeks. The rats which exhibited VCM eight times or more in 3min were selected on
      the 12th week, and examined. A significant increase in VCM on the 12th week
      continued until the 18th week. Oral administration of YKS (0.1 and 0.5g/kg) once
      a day for three weeks (21 days) from the 12th week to 15th week ameliorated the
      haloperidol decanoate-induced increase in VCM in a dose-dependent manner. The
      significant ameliorative effect observed in 0.5g/kg YKS-treated rats was
      abolished by stopping administration for three weeks from the 15th week to the
      18th week. The extracellular glutamate concentration and glutamate transporter
      mRNA expression in the striatum were evaluated by microdialysis and real-time
      reverse-transcription polymerase chain reaction assays at the 15th week. The
      striatal glutamate level increased in haloperidol-treated rats, and the increase
      was inhibited by treatment with YKS. The striatal GLT-1 mRNA level showed a
      tendency to decrease in the haloperidol-treated rats. The GLT-1 mRNA level after
      treatment with YKS (0.5g/kg) was greater than the control level. These results
      suggest the effect of YKS may be involved in the extracellular glutamate level
      and GLT-1 mRNA expression in the striatum.

PMID- 22982368
TI  - C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from
      transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced
      impairment.
AB  - Oxidative stress and mitochondrial impairment are essential in the ischemic
      stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has
      previously been shown to have strong antioxidant and neuroprotective actions. In
      the present study, we assessed the effects of C-PC on oxidative injury induced by
      tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia
      in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat
      brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant
      reduction of cell viability as assessed by an MTT assay, and the reduction was
      effectively prevented by treatment with C-PC in the low micromolar concentration
      range. Transient ischemia in rat retinas was induced by increasing the
      intraocular pressure to 120mmHg for 45min, which was followed by 15min of
      reperfusion. This event resulted in a cell density reduction to lower than 50% in
      the inner nuclear layer (INL), which was significantly prevented by the
      intraocular pre-treatment with C-PC for 15min. In the RBM exposed to 3mM
      phosphate and/or 100MUM Ca(2+), C-PC prevented in the low micromolar
      concentration range, the mitochondrial permeability transition as assessed by
      mitochondrial swelling, the membrane potential dissipation, the increase of
      reactive oxygen species levels and the release of the pro-apoptotic cytochrome c.
      In addition, C-PC displayed a strong inhibitory effect against an
      electrochemically-generated Fenton reaction. Therefore, C-PC is a potential
      neuroprotective agent against ischemic stroke, resulting in reduced neuronal
      oxidative injury and the protection of mitochondria from impairment.

PMID- 22982370
TI  - Using crowdsourcing to examine relations between delay and probability
      discounting.
AB  - Although the extensive lines of research on delay and/or probability discounting
      have greatly expanded our understanding of human decision-making processes, the
      relation between these two phenomena remains unclear. For example, some studies
      have reported robust associations between delay and probability discounting,
      whereas others have failed to demonstrate a consistent relation between the two.
      The current study sought to clarify this relation by examining the relation
      between delay and probability discounting in a large sample of internet users
      (n=904) using the Amazon Mechanical Turk (AMT) crowdsourcing service. Because AMT
      is a novel data collection platform, the findings were validated through the
      replication of a number of previously established relations (e.g., relations
      between delay discounting and cigarette smoking status). A small but highly
      significant positive correlation between delay and probability discounting rates
      was obtained, and principal component analysis suggested that two (rather than
      one) components were preferable to account for the variance in both delay and
      probability discounting. Taken together, these findings suggest that delay and
      probability discounting may be related, but are not manifestations of a single
      construct (e.g., impulsivity).

PMID- 22982369
TI  - Mitochondria in cardiac hypertrophy and heart failure.
AB  - Heart failure (HF) frequently is the unfavorable outcome of pathological heart
      hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in
      response to exercise and leads to full adaptation of contractility to the
      increased wall stress, pathological hypertrophy occurs in response to volume or
      pressure overload, ultimately leading to contractile dysfunction and HF. Because
      cardiac hypertrophy impairs the relationship between ATP demand and production,
      mitochondrial bioenergetics must keep up with the cardiac hypertrophic phenotype.
      We review data regarding the mitochondrial proteomic and energetic remodeling in
      cardiac hypertrophy, as well as the temporal and causal relationships between
      mitochondrial failure to match the increased energy demand and progression to
      cardiac decompensation. We suggest that the maladaptive effect of sustained
      neuroendocrine signals on mitochondria leads to bioenergetic fading which
      contributes to the progression from cardiac hypertrophy to failure. This article
      is part of a Special Issue entitled "Focus on Cardiac Metabolism".

PMID- 22982371
TI  - Adrenal nodular hyperplasia in hereditary leiomyomatosis and renal cell cancer.
AB  - PURPOSE: The condition hereditary leiomyomatosis and renal cell carcinoma is
      characterized by cutaneous leiomyomas, uterine fibroids and aggressive papillary
      renal cell carcinoma. A number of our patients with hereditary leiomyomatosis and
      renal cell carcinoma had atypical adrenal nodules, which were further evaluated
      to determine whether these nodules were associated with hereditary leiomyomatosis
      and renal cell carcinoma. MATERIALS AND METHODS: Patients with hereditary
      leiomyomatosis and renal cell carcinoma underwent a comprehensive clinical and
      genetic evaluation. We reviewed the clinical presentation, anatomical and
      functional imaging, endocrine evaluation, pathological examination and germline
      mutation testing results. RESULTS: Of 255 patients with hereditary leiomyomatosis
      and renal cell carcinoma 20 (7.8%) had primary adrenal lesions, including 4 with
      bilateral adrenal lesions and 4 with multiple nodules. Two patients had
      adrenocorticotropic hormone independent hypercortisolism. A total of 27 adrenal
      lesions were evaluated. The imaging characteristics of 5 of these lesions (18.5%)
      were not consistent with adenoma by noncontrast computerized tomography criteria.
      Positron emission tomography was positive in 7 of 10 cases (70%). A total of 12
      nodules were surgically resected from 10 adrenal glands. Pathological examination
      revealed macronodular adrenal hyperplasia in all specimens. CONCLUSIONS:
      Unilateral and bilateral adrenal nodular hyperplasia was detected in a subset of
      patients with hereditary leiomyomatosis and renal cell carcinoma. A functional
      endocrine evaluation is recommended when an adrenal lesion is discovered. Imaging
      frequently reveals lesions that are not typical of adenomas and positron emission
      tomography may be positive. To date no patient has had adrenal malignancy, and
      active surveillance of hereditary leiomyomatosis and renal cell carcinoma adrenal
      nodules appears justified.

PMID- 22982372
TI  - Pharmacological modulation of brain activity in a preclinical model of
      osteoarthritis.
AB  - The earliest stages of osteoarthritis are characterized by peripheral pathology;
      however, during disease progression chronic pain emerges-a major symptom of
      osteoarthritis linked to neuroplasticity. Recent clinical imaging studies
      involving chronic pain patients, including osteoarthritis patients, have
      demonstrated that functional properties of the brain are altered, and these
      functional changes are correlated with subjective behavioral pain measures.
      Currently, preclinical osteoarthritis studies have not assessed if functional
      properties of supraspinal pain circuitry are altered, and if these functional
      properties can be modulated by pharmacological therapy either by direct or
      indirect action on brain systems. In the current study, functional connectivity
      was first assessed in order to characterize the functional neuroplasticity
      occurring in the rodent medial meniscus tear (MMT) model of osteoarthritis-a
      surgical model of osteoarthritis possessing peripheral joint trauma and a
      hypersensitive pain state. In addition to knee joint trauma at week 3 post-MMT
      surgery, we observed that supraspinal networks have increased functional
      connectivity relative to sham animals. Importantly, we observed that early and
      sustained treatment with a novel, peripherally acting broad-spectrum matrix
      metalloproteinase (MMP) inhibitor (MMPi) significantly attenuates knee joint
      trauma (cartilage degradation) as well as supraspinal functional connectivity
      increases in MMT animals. At week 5 post-MMT surgery, the acute pharmacodynamic
      effects of celecoxib (selective cyclooxygenase-2 inhibitor) on brain function
      were evaluated using pharmacological magnetic resonance imaging (phMRI) and
      functional connectivity analysis. Celecoxib was chosen as a comparator, given its
      clinical efficacy for alleviating pain in osteoarthritis patients and its
      peripheral and central pharmacological action. Relative to the vehicle condition,
      acute celecoxib treatment in MMT animals yielded decreased phMRI infusion
      responses and decreased functional connectivity, the latter observation being
      similar to what was detected following chronic MMPi treatment. These findings
      demonstrate that an assessment of brain function may provide an objective means
      by which to further evaluate the pathology of an osteoarthritis state as well as
      measure the pharmacodynamic effects of therapies with peripheral or peripheral
      and central pharmacological action.

PMID- 22982373
TI  - EEG indices of reward motivation and target detectability in a rapid visual
      detection task.
AB  - A large corpus of data has demonstrated the sensitivity of behavioral and neural
      measures to variation in the availability of reward. The present study aimed to
      extend this work by exploring reward motivation in an RSVP task using complex
      satellite imagery. We found that reward motivation significantly influenced
      neural activity both in the preparatory period and in response to target images.
      Pre-stimulus alpha activity and, to a lesser degree, P3 and CNV amplitude were
      found to be significantly predictive of reward condition on single trials. Target
      locked P3 amplitude was modulated both by reward condition and by variation in
      target detectability inherent to our task. We further quantified this exogenous
      influence, showing that P3 differences reflected single-trial variation in P3
      amplitude for different targets. These findings provide theoretical insight into
      the neural indices of reward in an RSVP task, and have important applications in
      the field of satellite imagery analysis.

PMID- 22982374
TI  - Quantitative proteomic analysis reveals that antioxidation mechanisms contribute
      to cold tolerance in plantain (Musa paradisiaca L.; ABB Group) seedlings.
AB  - Banana and its close relative, plantain are globally important crops and there is
      considerable interest in optimizing their cultivation. Plantain has superior cold
      tolerance compared with banana and a thorough understanding of the molecular
      mechanisms and responses of plantain to cold stress has great potential value for
      developing cold tolerant banana cultivars. In this study, we used iTRAQ-based
      comparative proteomic analysis to investigate the temporal responses of plantain
      to cold stress. Plantain seedlings were exposed for 0, 6, and 24 h of cold stress
      at 8  degrees C and subsequently allowed to recover for 24 h at 28  degrees C. A
      total of 3477 plantain proteins were identified, of which 809 showed differential
      expression from the three treatments. The majority of differentially expressed
      proteins were predicted to be involved in oxidation-reduction, including oxylipin
      biosynthesis, whereas others were associated with photosynthesis,
      photorespiration, and several primary metabolic processes, such as carbohydrate
      metabolic process and fatty acid beta-oxidation. Western blot analysis and enzyme
      activity assays were performed on seven differentially expressed, cold-response
      candidate plantain proteins to validate the proteomics data. Similar analyses of
      the seven candidate proteins were performed in cold-sensitive banana to examine
      possible functional conservation, and to compare the results to equivalent
      responses between the two species. Consistent results were achieved by Western
      blot and enzyme activity assays, demonstrating that the quantitative proteomics
      data collected in this study are reliable. Our results suggest that an increase
      of antioxidant capacity through adapted ROS scavenging capability, reduced
      production of ROS, and decreased lipid peroxidation contribute to molecular
      mechanisms for the increased cold tolerance in plantain. To the best of our
      knowledge, this is the first report of a global investigation on molecular
      responses of plantain to cold stress by proteomic analysis.

PMID- 22982375
TI  - Single-cell-type proteomics: toward a holistic understanding of plant function.
AB  - Multicellular organisms such as plants contain different types of cells with
      specialized functions. Analyzing the protein characteristics of each type of cell
      will not only reveal specific cell functions, but also enhance understanding of
      how an organism works. Most plant proteomics studies have focused on using
      tissues and organs containing a mixture of different cells. Recent single-cell
      type proteomics efforts on pollen grains, guard cells, mesophyll cells, root
      hairs, and trichomes have shown utility. We expect that high resolution proteomic
      analyses will reveal novel functions in single cells. This review provides an
      overview of recent developments in plant single-cell-type proteomics. We discuss
      application of the approach for understanding important cell functions, and we
      consider the technical challenges of extending the approach to all plant cell
      types. Finally, we consider the integration of single-cell-type proteomics with
      transcriptomics and metabolomics with the goal of providing a holistic
      understanding of plant function.

PMID- 22982376
TI  - Lipocalin 2 is a novel regulator of angiogenesis in human breast cancer.
AB  - Lipocalin 2 (Lcn2), a member of the lipocalin family, is up-regulated in a
      variety of epithelial cancers. We have previously reported that Lcn2 induces the
      epithelial to mesenchymal transition in breast cancer through the estrogen
      receptor alpha/Slug axis and that it is a potential noninvasive biomarker of this
      disease. Here, we report the novel finding that Lcn2 regulates breast cancer
      angiogenesis. Vascular endothelial growth factor (VEGF), a key angiogenic
      activator, was significantly increased with Lcn2 expression in MCF-7 human breast
      cancer cells as well as in an angiogenic line derived from MDA-MB-436 cells.
      Treatment with a VEGF-neutralizing antibody demonstrates that VEGF is essential
      for the angiogenic activity of Lcn2. We further demonstrate that Lcn2-induced
      VEGF is mediated through hypoxia-inducible factor 1alpha (HIF-1alpha) and that
      Lcn2 regulates HIF-1alpha through extracellular signal-regulated kinase (Erk).
      The regulation of HIF-1alpha and VEGF by Lcn2 was also demonstrated in the
      aggressive MDA-MB-231 cell line. Using the mouse corneal pocket assay, we found
      that Lcn2 significantly enhanced the angiogenesis induced by VEGF. Taken
      together, these results are the first to demonstrate that Lcn2 promotes
      angiogenesis in vitro and in vivo and suggest a novel mechanism through which
      Lcn2 may promote tumor progression.

PMID- 22982378
TI  - The hepatic phosphatidylcholine transporter ABCB4 as modulator of glucose
      homeostasis.
AB  - The hepatic phosphatidylcholine (PC) transporter ATP-binding cassette (ABC) B4
      flops PC from hepatocytes into bile, and its dysfunction causes chronic
      cholestasis and fibrosis. Because a nuclear receptor-dependent PC pathway has
      been determined to exert antidiabetic effects, we now analyzed the role of ABCB4
      in glucose metabolism. We bred congenic Abcb4-knockout (Abcb4(-/-)) mice on the
      fibrosis-susceptible BALB/cJ background. Knockout mice and wild-type controls
      were phenotyped by measuring plasma glucose concentrations, intraperitoneal
      glucose tolerance, hepatic RNA expression profiles, and liver histology. In
      addition, 4 procholestatic ABCB4 gene variants were correlated with blood glucose
      levels in 682 individuals from 2 independent European cohorts. Systemic glucose
      levels differ significantly between Abcb4(-/-) mice and wild-type controls, and
      knockout mice display improved glucose tolerance with significantly lower area
      under the curve values on intraperitoneal glucose challenge. Of note, hepatic
      expression of the antidiabetic nuclear receptor 5A2 (LRH-1) is induced
      consistently in Abcb4(-/-) mice, and its specific rare PC ligands are detected in
      liver by mass spectrometry imaging. In humans, serum glucose levels are
      associated significantly with the common ABCB4 variant c.711A>T. In summary,
      ABCB4 might play a critical role in glucose homeostasis in mice and humans. We
      speculate that the effects could be mediated via LRH-1-dependent PC pathways.

PMID- 22982377
TI  - A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase
      activity in nonhuman primates.
AB  - In nonhuman primates, we previously demonstrated that a maternal high-fat diet
      (MHFD) induces fetal nonalcoholic fatty liver disease (NAFLD) and alters the
      fetal metabolome. These changes are accompanied by altered acetylation of histone
      H3 (H3K14ac). However, the mechanism behind this alteration in acetylation
      remains unknown. As SIRT1 is both a lysine deacetylase and a crucial sensor of
      cellular metabolism, we hypothesized that SIRT1 may be involved in fetal
      epigenomic alterations. Here we show that in utero exposure to a MHFD, but not
      maternal obesity per se, increases fetal H3K14ac with concomitant decreased SIRT1
      expression and diminished in vitro protein and histone deacetylase activity. MHFD
      increased H3K14ac and DBC1-SIRT1 complex formation in fetal livers, both of which
      were abrogated with diet reversal despite persistent maternal obesity. Moreover,
      MHFD was associated with altered expression of known downstream effectors
      deregulated in NAFLD and modulated by SIRT1 (e.g., PPARAlpha, PPARG, SREBF1,
      CYP7A1, FASN, and SCD). Finally, ex vivo purified SIRT1 retains deacetylase
      activity on an H3K14ac peptide substrate with preferential activity toward
      acetylated histone H3; mutagenesis of the catalytic domain of SIRT1 (H363Y)
      abrogates H3K14ac deacetylation. Our data implicate SIRT1 as a likely molecular
      mediator of the fetal epigenome and metabolome under MHFD conditions.

PMID- 22982379
TI  - Allosteric interaction between 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4
      isomerase and cytochrome b5 influences cofactor binding.
AB  - The biosynthesis of steroid hormones, essential to the survival of all mammals,
      is dependent on the activity of 3beta-hydroxysteroid dehydrogenase/Delta(5)
      Delta(4) isomerase (3betaHSD). 3betaHSD activity is, in turn, influenced by
      cytochrome-b(5) (Cyt-b(5)). However, the mechanism through which this occurs is
      unknown. In this study, we investigated this mechanism by evaluating the
      influence of Cyt-b(5) on the dehydrogenase and isomerase activities of 3betaHSD.
      Capra hircus 3betaHSD was overexpressed in SF-9 cells, using a baculovirus
      expression system, and purified. Substrate and cofactor kinetics were determined
      spectrophotometrically in the presence and absence of purified Ovis aries liver
      Cyt-b(5). Nonspecific enzyme activity was evaluated by zero-enzyme, -substrate,
      and -cofactor blanks. Fusion proteins, 3betaHSD-eCFP, and Cyt-b(5)-eYFP were
      subsequently coexpressed in COS-1 cells and analyzed for FRET. A CFP-YFP fusion
      protein served as positive control, while coexpression of 3betaHSD-eCFP and
      cytochrome P450 17alpha-hydroxylase/17,20 lyase-eYFP (CYP17A1-eYFP) served as
      negative control. Results showed Cyt-b(5) to decrease the K(m,)(NAD(+)) value of
      3betaHSD ~3.5-fold while increasing the V(max,app) of the dehydrogenase reaction
      ~17%. FRET analysis showed COS-1 cells coexpressing 3betaHSD-eCFP and Cyt-b(5)
      eYFP to exhibit a FRET signal ~9-fold greater than that of the negative control.
      These results indicate that Cyt-b(5) augments 3betaHSD activity via an allosteric
      mechanism by increasing the affinity of the enzyme toward NAD(+).

PMID- 22982380
TI  - Molecular structure and vibrational spectra of Irinotecan: a density functional
      theoretical study.
AB  - The solid phase FTIR and FT-Raman spectra of Irinotecan have been recorded in the
      regions 400-4000 and 50-4000 cm(-1), respectively. The spectra were interpreted
      in terms of fundamentals modes, combination and overtone bands. The structure of
      the molecule was optimized and the structural characteristics were determined by
      density functional theory (DFT) using B3LYP method with 6-31G(d) as basis set.
      The vibrational frequencies were calculated for Irinotecan by DFT method and were
      compared with the experimental frequencies, which yield good agreement between
      observed and calculated frequencies. The infrared spectrum was also simulated
      from the calculated intensities. Besides, molecular electrostatic potential
      (MEP), frontier molecular orbitals (FMO) analysis were investigated using
      theoretical calculations.

PMID- 22982381
TI  - Studies on synthesis, growth, structural, thermal, linear and nonlinear optical
      properties of organic picolinium maleate single crystals.
AB  - Picolinium maleate (PM), an organic material has been synthesised and single
      crystals were grown by slow evaporation technique. The structure of the grown
      crystal was elucidated by using single crystal X-ray diffraction analysis. PM
      crystal belongs to the monoclinic crystallographic system with space group
      P2(1)/c. The crystalline perfection of the grown crystals was analyzed by high
      resolution X-ray diffraction rocking curve measurements. The presence of
      functional groups in PM was identified by FTIR and FT-NMR spectral analyses.
      Thermal behaviour and stability of picolinium maleate were studied by TGA/DTA
      analyses. UV-Vis spectral studies reveal that PM crystals are transparent in the
      wavelength region 327-1100 nm. The laser damage threshold value of PM crystal was
      found to be 4.3 GW/cm(2) using Nd:YAG laser. The Kurtz and Perry powder second
      harmonic generation technique confirms the nonlinear optical property of the
      grown crystal.

PMID- 22982382
TI  - Fe(3+)-selective fluorescent probe based on aminoantipyrine in aqueous solution.
AB  - A novel and simple Schiff base composed with 9-anthraldehyde and 4
      aminoantipyrine was synthesized and characterized as a fluorescent probe. In the
      presence of Fe(3+), the fluorescent intensity has a dramatic enhancement over
      other examined metal ions in aqueous solution. The method of Job's plot indicated
      the formation of 1:1 complex between probe and Fe(3+), and the possible binding
      mode of the system was also proposed. Moreover, other examined metal ions had no
      effect on the detection of Fe(3+).

PMID- 22982383
TI  - In search of the thermo/halochromism of the E(T)(30) pyridinium-N-phenolate
      betaine dye.
AB  - The thermohalochromic behavior of Reichardt's E(T)(30) betaine - the temperature
      dependent variation of its halochromic band in the presence of a cation - was
      investigated for the first time in NaI solutions of HBD- (methanol, ethanol, 1
      propanol, 1-butanol) and non-HBD-solvents (acetonitrile, dimethylformamide) at 15
      and 55  degrees C. The solvent-dependent thermohalochromism of the pyridinium-N
      phenolate betaine dye was interpreted in terms of the effect of the temperature
      on the dye-cation association in solution.

PMID- 22982384
TI  - Modulation of synthetic parameters of cobalt nanoparticles: TEM, EDS, spectral
      and thermal studies.
AB  - The study focuses on the modulation of synthetic parameters in order to influence
      the size, structure, composition and arrangement of nanoparticles of cobalt.
      Cobalt nanoparticles were synthesized by ethanolic solution of
      benzildiethylenetriamine in cobalt nitrate solution at 60  degrees C with
      stirring and refluxing leads to nanoparticles of cobalt. The morphology and
      structure of the synthesized nanoparticles of cobalt were characterized by
      Transmission Electron Microscopy (TEM), Powder X-ray Diffraction (XRD), Thermal
      Gravimetric Analysis (TGA), QELS Data and Infrared Spectroscopy (IR). Crystalline
      size was 20 nm determined from the sharp peak at 2theta=25  degrees C from the
      powder XRD. TEM images of cobalt nanoparticles without reducing agent having the
      diameter 20 nm with spherical shape and black color.

PMID- 22982385
TI  - A DFT/TDDFT study on spectral effects of metal ion interactions with benzofurazan
      based fluorescent probes.
AB  - CAM-B3LYP DFT/TDDFT calculations have been performed on two fluorescent
      benzofurazan derivatives and their complexes with metal ions (Zn(2+), Na(+),
      K(+), Mg(2+) and Ca(2+)). Optimized structures of complexes and binding energies
      have been determined. Calculated vertical transition energies have been compared
      to available experimental data. Only one ligand binds effectively Zn(2+) ion
      allowing metal orbitals to participate in frontier molecular orbitals which
      results in significant shifts in absorption and emission spectra. Modified
      structure of the other ligand makes ion binding less effective. It has been shown
      that proper reproduction of transition energies requires accounting for state
      specific solvation.

PMID- 22982386
TI  - Synthesis and characterization of VO(II), Co(II), Ni(II), Cu(II) and Zn(II)
      complexes of chromone based azo-linked Schiff base ligand.
AB  - Azo-Schiff-base complexes of VO(II), Co(II), Ni(II), Cu(II) and Zn(II) have been
      synthesized and characterized by elemental analysis, IR, UV-Vis, (1)H NMR, mass
      spectra, molar conductance, magnetic susceptibility measurement, electron spin
      resonance (EPR), CV, fluorescence, NLO and SEM. The conductance data indicate the
      nonelectrolytic nature of the complexes, except VO(II) complex which is
      electrolytic in nature. On the basis of electronic spectra and magnetic
      susceptibility octahedral geometry has been proposed for the complexes. The EPR
      spectra of copper and oxovanadium complexes in DMSO at 300 and 77K were recorded
      and its salient features are reported. The redox behavior of the copper(II)
      complex was studied using cyclic voltammetry. The in vitro antimicrobial activity
      against Staphylococcus aureus, Escherichia coli, Salmonella enterica typhi,
      Bacillus subtilis and Candida strains was studied and compared with that of free
      ligand by well-diffusion technique. The azo Schiff base exhibited fluorescence
      properties originating from intraligand (pi-pi(*)) transitions and metal-mediated
      enhancement is observed on complexation and so the synthesized complexes can
      serve as potential photoactive materials as indicated from their characteristic
      fluorescence properties. On the basis of the optimized structures, the second
      order nonlinear optical properties (NLO) are calculated by using second-harmonic
      generation (SHG) and also the surface morphology of the complexes was studied by
      SEM.

PMID- 22982387
TI  - Spectroscopic isotope ratio measurement of doubly-substituted methane.
AB  - We have determined the isotope ratios of (13)CH(3)D /(12)CH(3)D as well as
      (13)CH(3)D /(12)CH(4) with an uncertainty of ~200/00 using a sensitive difference
      frequency-generation spectrometer in the 3.4 MUm region. Cooling the absorption
      cell drastically reduces overlap of the (13)CH(3)D lines with the other abundant
      isotopic lines, and the extensive tunability of the spectrometer enables us to
      access transition pairs appropriate for isotope ratio measurements. We measure
      the intensity of the (13)CH(3)D nu(4)(R)P (7, 0) line, the (12)CH(3)D 2nu(5)(R)Q
      (9, 0) line, and the (12)CH(4)nu(2)+nu(4) R(10) F(2) line at 2953 cm(-1) as well
      as the (13)CH(3)D nu(4)(P)P (6, 3) line and the (12)CH(4)nu(3) P (6) E line at
      2955 cm(-1) because they have similar transition frequencies, absorption
      strengths, and low state energies.

PMID- 22982388
TI  - Near-infrared spectroscopy study for determination of adsorbed acetochlor in the
      organic and inorganic bentonites.
AB  - NIR spectroscopy is used to determine acetochlor herbicide adsorption on Na
      montmorillonite (NaP) and organically modified montmorillonite (NaOM). Both
      montmorillonites NIR spectra shows bands at 7061 and 6791 cm(-1). Organo
      montmorillonite is characterised by two emphasized bands at 5871 and 5667 cm(-1)
      that are attributed to the fundamental overtones of the mid-IR bands at 2916 and
      2850 cm(-1). Bands at 6017 and 6013 cm(-1) are attributed to acetochlor adsorbed
      to organo-montmorillonite and Na-montmorillonite, which is confirmed by X-ray
      powder diffraction (XRPD). Greater quantity of acetochlor is adsorbed to organo
      clays compared to non-modified montmorillonite. Acetochlor poses high risk to
      environmental contamination. Organo-clays are the most useful for removing
      acetochlor from water and soil.

PMID- 22982389
TI  - Metal based new triazoles: their synthesis, characterization and
      antibacterial/antifungal activities.
AB  - A series of new triazoles and their oxovanadium(IV) complexes have been
      synthesized, characterized and evaluated for antibacterial/antifungal properties.
      The new Schiff bases ligands (L(1))-(L(5)) were prepared by the condensation
      reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2
      carboxaldehyde, pyridine-2-carboxaldehyde, 2-acetyl pyridine and 2-methoxy
      benzaldehyde. The structures of the ligands have been established on the basis of
      their physical, spectral (IR, (1)H and (13)C NMR and mass spectrometry) and
      elemental analytical data. The prepared ligands were used to synthesize their
      oxovanadium(IV) complexes (1)-(5) which were also characterized by their
      physical, spectral and analytical data and proposed to have a square pyramidal
      geometry. The ligands and their complexes were screened for in vitro
      antibacterial activity against six bacterial species such as, Escherichia coli,
      Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus
      aureus, and Bacillus subtilis and for in vitro antifungal activity against six
      fungal strains, Trichophyton longifusus, Candida albicans, Aspergillus flavus,
      Microsporum canis, Fusarium solani, and Candida glabrata. Cytotoxic nature of the
      compounds was also reported using brine shrimp bioassay method against Artemia
      salina.

PMID- 22982390
TI  - Dinuclear triple-stranded complexes of Re(V) with bis(benzene-o-dithiolato)
      ligands.
AB  - The reaction of K(2)ReCl(6) with 1,2-bis(2,3-dimercaptobenzamido)ethane (H(4)-1),
      and 1,2-bis(2,3-dimercaptobenzamido)benzene (H(4)-2) in the presence of
      Na(2)CO(3) in methanol affords dinuclear complexes of Re(V). Experimental
      evidence supports the presence of self-assembled complexes with two
      {Re(S(2)C(6)H(3))(3)} units connected in a triple-stranded fashion. Density
      Functional Theory (DFT) studies on geometry and electronic properties were
      conducted employing the hybrid B3LYP and PBE1PBE functionals. The helical
      (DeltaDelta and LambdaLambda) and meso-helical (DeltaLambda) isomers were
      considered. For the helicate complexes included in this study, differences in the
      stability of the isomers were observed originating in different steric and strain
      interactions between the three ligand strands. The geometries at the minimum
      exhibit a distorted trigonal-prismatic coordination environment at the metal
      centers. Natural bond orbitals (NBO) analysis indicates the presence of Re-S
      bonds which are strongly polarized toward the non-metal. Time-Dependent DFT (TD
      DFT) calculations were performed for a further understanding of the optical
      spectra. The calculations show the occupied 5d orbitals of the rhenium lying
      beneath occupied sulfur-based MOs. The general features of the electronic spectra
      in the visible region are reasonably reproduced by the calculations. The analysis
      of molecular orbitals also allows the assignment of the origin for all
      experimentally detected absorption bands. In the high-energy region of the
      spectrum the absorptions are attributed to ligand-to-metal-ligand charge transfer
      (LMLCT), in which sulfur-based orbitals and unoccupied orbitals at the rhenium
      atom and the benzene-o-dithiolato groups are involved. Also in the blue region,
      shoulders originating from LMLCT are observed.

PMID- 22982391
TI  - Optical spectroscopy studies of the complexation of bis(azophenol)calix[4]arene
      possessing chromogenic donors with Ni2+, Co2+, Cu2+, Pb2+ and Hg2+.
AB  - Due to their potential applicability as selective receptors in electrochemical or
      optical sensors, a bis(azophenol)calix[4]arene derivative H(2)L has been
      investigated. The complexation properties of this molecule towards Ni(2+) and
      Co(2+) metal ions has been studied. It is revealed that this ligand exhibits
      tetradentate with N(2)O(2) core when bound to Ni (II) or Co (II) metal ion. The
      optical response of azo groups of H(2)L towards Ni(2+), Co(2+), Cu(2+), Pb(2+)
      and Hg(2+) metal ions has been investigated in DMSO by UV-vis spectroscopy. The
      absorption spectra of calix[4]arene with cations show marked changes, especially
      for Co(2+) ion. Furthermore, Job's plot indicate 1:1 binding-stiochiometry for
      calix[4]arene with Co(2+) ion and Benson-Hilderbrand plot is used for the
      determination of its association constant. The investigation of UV-vis spectra of
      chromogenic calix[4]arene in different solvents shows that cis-trans
      isomerization of azo groups probably depends on kind of solvent. Also the
      different between the polarity and viscosity of organic solvents used is likely
      responsible for the changes of the band shape of the spectra.

PMID- 22982392
TI  - Ethnopharmacology guided screening of traditional Indian herbs for selective
      inhibition of Plasmodium specific lactate dehydrogenase.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants traditionally used to treat
      malaria can provide quality leads towards identifying novel anti-malarial drugs.
      Here we combined this approach with target based drug discovery and explored
      Plasmodium specific lactate dehydrogenase (LDH) inhibitory activity of 8 Indian
      plants which are ethnically used to treat malaria. METHODS: LDH from Indian
      Plasmodium falciparum and Plasmodium vivax strains, were cloned and expressed in
      Escherichia coli, followed by purification of recombinant enzymes (rPfLDH and
      rPvLDH respectively). Extracts of 8 plants in different organic and aqueous
      solvents, were screened for their inhibitory activity on rPfLDH, rPvLDH and
      mammalian LDHs. Phyllanthus amarus aqueous extract was further tested for in
      vitro parasiticidal activity. RESULTS: Aqueous extract of Phyllanthus amarus
      Schum. and Thonn. and chloroform extract of Murraya koenigii (L.) Spreng.
      exhibited profound and exclusive inhibitory effect on Plasmodium falciparum LDH
      (IC(50)=11.2 MUg/ml +/- 0.4) and Plasmodium vivax LDH (IC(50)=6.0 MUg/ml +/- 0.6)
      respectively. Moreover, Phyllanthus amarus aqueous extract also demonstrated
      antiplasmodial activity in vitro, on Chloroquine sensitive and resistant strains
      of Plasmodium falciparum (IC(50)=7.1 MUg/ml +/- 0.5 and 6.9 MUg/ml +/- 0.7
      respectively). CONCLUSION: Target specific screening of traditional herbs used in
      malaria treatment has proffered Phyllanthus amarus and Murraya koenigii extracts
      as hits which can optimistically provide novel antimalarial drugs.

PMID- 22982393
TI  - Chicken embryo extracts enhance spleen lymphocyte and peritoneal macrophages
      function.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, chicken embryo eggs are widely
      considered as an immunomodulatory health product in China and southeast Asia.
      Besides that, Compendium of Materia Medica, the most famous Chinese
      pharmacopoeia, has recorded that chicken embryo eggs contributed to the appetite
      increase and immune function enhancement, especially for the pregnant and aged.
      AIM OF THE STUDY: Through assessing the immune efficacy of the chicken embryo
      extracts on immunocompetent cells, the immunomodulatory mechanism and components
      were explored preliminarily. MATERIALS AND METHODS: The raw material was
      subjected to in vitro gastric and pancreatic digestion successively, and then
      ligarine was added to separate the digested mixture to water-soluble fraction
      (WS) and lipid-soluble fraction (LS). Employing in vitro cell models, the
      immunomodulating activities of the extracts on immunosuppressed mouse were
      examined, at concentrations ranging from 10 to 500 MUg/ml. The cell experiments
      consisted of the following experiments: spleen lymphocyte proliferation and IL-2
      secretion, peritoneal macrophage phagocytosis and NO production. Before cell
      experiments, Kjeldal method and phenol-sulfuric acid method were employed
      respectively to determine the total protein and polysaccharide content of WS, and
      gas chromatography to analyze the fatty acid composition of LS. RESULTS: LS
      significantly enhanced the spleen lymphocyte proliferation and IL-2 secretion,
      while peritoneal macrophage phagocytosis and NO production activity were elevated
      by WS. Both extracts exhibited an immunomodulatory effect with a dose-effect
      relationship. CONCLUSION: The findings confirmed the chicken embryo eggs as a
      potent immunopotentiator on the immunosuppressed mouse, which would be useful for
      the fruitful application of the chicken embryo eggs to serve as a superior
      immunostimulatory tonic. Furthermore, the two extracts exhibited a different
      bioactivity tendency which makes it a significative work to screen the bioactive
      component for further study.

PMID- 22982394
TI  - Hepatoprotective and antiviral properties of isochlorogenic acid A from Laggera
      alata against hepatitis B virus infection.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this study was to determine the anti
      hepatitis B effect of isochlorogenic acid A isolated from Laggera alata
      (Asteraceae), a traditional Chinese herbal medicine. MATERIALS AND METHODS: The
      anti-hepatitis B activity of isochlorogenic acid A was evaluated by the D
      galactosamine (D-GalN)-induced HL-7702 hepatocyte damage model and the HBV
      transfected HepG2.2.15 cells. RESULTS: Isochlorogenic acid A significantly
      improved HL-7702 hepatocyte viability and markedly inhibited the productions of
      HBsAg and HBeAg. The inhibitory rates of isochlorogenic acid A on the HBsAg and
      HBeAg expressions were 86.9% and 72.9%, respectively. In addition, isochlorogenic
      acid A declined markedly the content of hepatitis B virus covalently closed
      circular DNA (HBV cccDNA) and induced significantly the heme oxygenase-1 (HO-1)
      expression in HepG2.2.15 cells. CONCLUSIONS: Isochlorogenic acid A was verified
      to possess the potent anti-hepatitis B activity. The anti-HBV target of
      isochlorogenic acid A is probably associated with blocking the translation step
      of the HBV replication. Overexpression of HO-1 may contribute to the anti-HBV
      activity of isochlorogenic acid A by reducing the stability of the HBV core
      protein and thus blocking the refill of nuclear HBV cccDNA. Additionally, the
      hepatoprotective effect of isochlorogenic acid A could be achieved by its
      antioxidative property and induction of HO-1.

PMID- 22982395
TI  - Investigation into the anti-thrombosis effect and contents of total saponins and
      flavonoids in the bioactive fraction of Naodesheng prescription.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Naodesheng prescription is a widely used
      traditional Chinese medicine (TCM), and mainly applied in clinics to treat
      cerebral arteriosclerosis, ischemic stroke, sequelae of cerebral hemorrhage etc.
      AIM OF THE STUDY: The present study was designed to investigate the anti
      thrombosis effects of this prescription, and to search its bioactive fraction.
      MATERIALS AND METHODS: We evaluated the anti-thrombotic effects by measuring
      platelet aggregation in rats, and the clotting time and protection rate in mice.
      The contents of total saponins and flavonoids in the bioactive fraction were
      determined by UV-vis spectrophotometry. RESULTS: The results showed that
      Naodesheng has significant anti-thrombotic and anticoagulation effects. The
      contents of total saponins and flavonoids in the bioactive fraction were 7.885%
      and 8.434%, respectively. CONCLUSIONS: Such study will contribute to further
      exploration of Naodesheng in the therapy of thrombosis diseases and to its re
      development based on the bioactive fraction and ingredients.

PMID- 22982396
TI  - Oncogene Ras/phosphatidylinositol 3-kinase signaling targets histone H3
      acetylation at lysine 56.
AB  - It is well established that the small GTPase Ras promotes tumor initiation by
      activating at least three different mediators: Raf, PI3K, and Ras-like (Ral)
      guanine nucleotide exchange factors. However, the exact mechanisms that underlie
      these different Ras signaling pathways, which are involved in tumor progression,
      remain to be elucidated. In this study, we report that the Ras-PI3K pathway, but
      not Raf or the Ral guanine nucleotide exchange factors, specifically targets the
      acetylation of H3 at lysine 56 (H3K56ac), thereby regulating tumor cell activity.
      We demonstrate that the Ras-PI3K-induced reduction in H3K56ac is associated with
      the proliferation and migration of tumor cells by targeting the transcription of
      tumor-associated genes. The depletion of the histone deacetyltransferases Sirt1
      and Sirt2 rescues the Ras-PI3K-induced decrease in H3K56ac, gene transcription,
      tumor cell proliferation, and tumor cell migration. Furthermore, we demonstrate
      that the Ras-PI3K-AKT pathway regulates H3K56ac via the MDM2-dependent
      degradation of CREB-binding protein/p300. Taken together, the results of this
      study demonstrate that the Ras-PI3K signaling pathway targets specific epigenetic
      modifications in tumor cells.

PMID- 22982398
TI  - Drug pipeline in neurodegeneration based on transgenic mice models of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is one of the most important neurodegenerative
      disorders, bringing about huge medical and social burden in the elderly
      worldwide. Many aspects of its pathogenesis have remained unclear and no
      effective treatment exists for it. Within the past 20 years, various mice models
      harboring AD-related human mutations have been produced. These models imitate
      diverse AD-related pathologies and have been used for basic and therapeutic
      investigations in AD. In this regard, there are a wide variety of preclinical
      trials of potential therapeutic modalities using AD mice models which are of
      paramount importance for future clinical trials and applications. This review
      summarizes more than 140 substances and treatment modalities being used in
      transgenic AD mice models from 2001 to 2011. We also discuss advantages and
      disadvantages of each model to be used in therapeutic development for AD.

PMID- 22982397
TI  - T-cell acute leukemia 1 (TAL1) regulation of erythropoietin receptor and
      association with excessive erythrocytosis.
AB  - During erythropoiesis, erythropoietin stimulates induction of erythroid
      transcription factors that activate expression of erythroid genes including the
      erythropoietin receptor (EPO-R) that results in increased sensitivity to
      erythropoietin. DNA binding of the basic helix-loop-helix transcription factor,
      TAL1/SCL, is required for normal erythropoiesis. A link between elevated TAL1 and
      excessive erythrocytosis is suggested by erythroid progenitor cells from a
      patient that exhibits unusually high sensitivity to erythropoietin with
      concomitantly elevated TAL1 and EPO-R expression. We found that TAL1 regulates
      EPO-R expression mediated via three conserved E-box binding motifs (CAGCTG) in
      the EPO-R 5' untranslated transcribed region. TAL1 increases association of the
      GATA-1.TAL1.LMO2.LDB1 transcription activation complex to the region that
      includes the transcription start site and the 5' GATA and 3' E-box motifs
      flanking the EPO-R transcription start site suggesting that TAL1 promotes
      accessibility of this region. Nucleosome shifting has been demonstrated to
      facilitate TAL1 but not GATA-1 binding to regulate target gene expression.
      Accordingly, we observed that with induced expression of EPO-R in hemotopoietic
      progenitor cells, nucleosome phasing shifts to increase the linker region
      containing the EPO-R transcription start site and TAL1 binds to the flanking 5'
      GATA and 3' E-box regions of the promoter. These data suggest that TAL1 binds to
      the EPO-R promoter to activate EPO-R expression and provides a potential link to
      elevated EPO-R expression leading to hypersensitivity to erythropoietin and the
      resultant excessive erythrocytosis.

PMID- 22982399
TI  - Improved processing of secretory proteins in Hansenula polymorpha by sequence
      variation near the processing site of the alpha mating factor prepro sequence.
AB  - The literature as well as databases are ambiguous about the exact start of human
      interleukin-6 (IL-6)--three possibilities for the initiation of the mature
      protein are described. These three variants of IL-6, different in the exact
      initiation of the mature protein (A28, P29, or V30), were expressed in Hansenula
      polymorpha using the Saccharomyces cerevisiae MFalpha prepro sequence instead of
      the homologous pre sequence. All three IL-6 variants were secreted but the
      processing by the Kex2 protease showed significant differences. V30-IL-6 showed
      correctly processed material but also a molecule species of higher molecular
      weight indicating incomplete processing of the MFalpha pro peptide. P29-IL-6 did
      not yield any correctly processed IL-6, instead only the unprocessed pro form was
      found in the culture supernatant. Only A28-IL-6 led to 100% correctly processed
      material. N-terminal sequencing of this material revealed a start at V30-
      obviously the first two amino acids (Ala28-Pro29) have been removed by a so far
      unknown protease. Thus expression of both A28-IL-6 and V30-IL-6 as MFalpha prepro
      fusion proteins resulted in the very same mature V30-IL-6, however, the ratio of
      correctly processed molecules was significantly higher in the case of A28-IL-6.
      The expression of an MFalpha prepro-interferon alpha-2a (IFNalpha-2a) fusion
      protein in H. polymorpha leads to about 50% correctly processed molecules and 50%
      misprocessed forms which contain part of the pro peptide at the N-termini. The
      insertion of A28 and P29 of IL-6 between the pro peptide and the start of the
      mature IFNalpha-2a led to correct processing and elimination of all high
      molecular weight isoforms observed in earlier experiments.

PMID- 22982400
TI  - Towards the in vivo production of tocotrienol compounds: engineering of a plasmid
      free Escherichia coli strain for the heterologous synthesis of 2-methyl-6
      geranylgeranyl-benzoquinol.
AB  - The vitamin E family consists of 4 tocopherol and 4 tocotrienol compounds. During
      recent years, tocotrienols have gained increased interest due to their biological
      activities that are beyond the vitamin E activity. Here we report the engineering
      of plasmid-free Escherichia coli strains for an efficient synthesis of 2-methyl-6
      geranylgeranyl-benzoquinol (MGGBQ), the central precursor for all four natural
      tocotrienol compounds. Heterologous genes needed for the in vivo synthesis of
      MGGBQ in E. coli (crtE, hpd, and hpt) were individually integrated into the
      chromosome of E. coli. The yield of MGGBQ after cultivation of the plasmid-free
      recombinant E. coli strain was significantly higher (604MUg/gcdw) compared to an
      E. coli strain that carries these biosynthesis genes on a multi-copy expression
      plasmid (325MUg/gcdw). Further chromosomal integration of an additional copy of
      the isopentenyl-diphosphate isomerase gene (idi) and a subsequent increase in
      expression level of the deoxy-xylulose synthase gene (dxs) increased the MGGBQ
      yield by 80% (1110MUg/gcdw) and 135% (1425MUg/gcdw), respectively. MGGBQ which
      accumulated in the membrane fraction of the recombinant E. coli cells was
      isolated and its structure was completely elucidated by 1D and 2D NMR and MS
      measurements. The engineered, plasmid-free E. coli strain is a promising host for
      the heterologous in vivo production of tocotrienol and its derivatives.

PMID- 22982401
TI  - High-throughput screening with a miniaturized radioligand competition assay
      identifies new modulators of human alpha2-adrenoceptors.
AB  - Human alpha(2)-adrenoceptors (alpha(2)-ARs) are rhodopsin-like G-protein coupled
      receptors, and potential drug targets. The three different human alpha(2)-AR
      subtypes alpha(2A), alpha(2B) and alpha(2C) are widely distributed in tissues,
      but so far only a few subtype-selective ligands have been identified. In this
      project, we set off to conduct a large chemical screen for activity on the human
      alpha(2B)-AR and studied the selectivity of the active compounds towards the
      human alpha(2A)- and alpha(2C)-AR subtypes. We employed a radioligand competition
      binding assay that was optimized and miniaturized into a robotic environment.
      Membrane fractions containing recombinant human receptor subtypes were prepared
      from stably transfected Chinese hamster ovary (CHO) cell lines. Initially
      identified hits were followed up and characterized, and chemoinformatics tools
      were applied to gain better understanding of the relevance of the results. After
      a primary screen against alpha(2B)-AR, 176 compounds of the 17,952 included in
      the library were declared as active at 10 MUM, of which 89 compounds were further
      selected for potency and affinity determinations using the three human alpha(2)
      AR subtypes. One of the identified positive hits was 2",2""-Bisepigallocatechin
      digallate, which was found to have high affinity at all three human alpha(2)-AR
      subtypes. This represents the first non-protonable molecule identified as able to
      interact with these receptors. Additionally, results obtained with a functional
      assay (agonist-induced stimulation of [(35)S]GTPgammaS binding) supported the
      identification of another positive hit, lysergol, as a partial agonist of the
      human alpha(2)-AR subtypes. The dataset of confirmed active chemical species
      represents a readily available, high quality source for follow-up studies.
      Altogether, these results provide novel research approaches for drug discovery of
      modulators of the alpha(2)-AR subtypes.

PMID- 22982402
TI  - A cell penetrating peptide-integrated and enediyne-energized fusion protein shows
      potent antitumor activity.
AB  - Arginine-rich peptides belong to a subclass of cell penetrating peptides that are
      taken up by living cells and can be detected freely diffusing inside the
      cytoplasm and nucleoplasm. This phenomenon has been attributed to either an
      endocytotic mode of uptake and a subsequent release from vesicles or a direct
      membrane penetration. Lidamycin is an antitumor antibiotic, which consists of an
      active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). In
      the present study, a fusion protein (Arg)(9)-LDP composed of cell penetrating
      peptide (Arg)(9) and LDP was prepared by DNA recombination, and the enediyne
      energized fusion protein (Arg)(9)-LDP-AE was prepared by molecular
      reconstitution. The data in fixed cells demonstrated that (Arg)(9)-LDP could
      rapidly enter cells, and the results based on fluorescence activated cell sorting
      indicated that the major route for (Arg)(9)-mediated cellular uptake of protein
      molecules was endocytosis. (Arg)(9)-LDP-AE demonstrated more potent cytotoxicity
      against different carcinoma cell lines than lidamycin in vitro. In the mouse
      hepatoma 22 model, (Arg)(9)-LDP-AE (0.3mg/kg) suppressed the tumor growth by
      89.2%, whereas lidamycin (0.05 mg/kg) by 74.6%. Furthermore, in the glioma U87
      xenograft model in nude mice, (Arg)(9)-LDP-AE at 0.2mg/kg suppressed tumor growth
      by 88.8%, compared with that of lidamycin by 62.9% at 0.05 mg/kg. No obvious
      toxic effects were observed in all groups during treatments. The results showed
      that energized fusion protein (Arg)(9)-LDP-AE was more effective than lidamycin
      and would be a promising candidate for glioma therapy. In addition, this approach
      to manufacturing fusion proteins might serve as a technology platform for the
      development of new cell penetrating peptides-based drugs.

PMID- 22982403
TI  - Role of convection and diffusion on DCE-MRI parameters in low leakiness KHT
      sarcomas.
AB  - The solid tumor is an abnormal environment that is resistant to systemically
      delivered drugs. Increased plasma leakiness and extracellular matrix density
      along with poor lymphatic function can result in interstitial flow that
      attenuates the effectiveness of therapeutics. This study expands upon a
      previously presented magnetic resonance (MR) imaging-based porous media model by
      investigating low permeability tumors, where interstitial flow may have increased
      effect on systemically delivered solutes. The solute transport of the porous
      media model is compared to that of experiment and the two-compartment model.
      Small non-necrotic tumors (n=3) were MR-imaged, serially, for 90 min after a
      bolus injection of Gd-based contrast agent (CA). These data provided for the
      calculation of experimental CA concentration over 90 min, while only early time
      points (15 min) were used to create vascular permeability, K(trans), maps for the
      porous media model. A K(trans) scale factor (range=1.3-2.5) in the porous media
      model was found to account for the reduction of permeability (measured by two
      compartment model) due to interstitial flow. The optimized porous media
      simulations showed: 1) better dynamic CA behavior agreement with the experimental
      data than the two-compartment model (>33% reduction of RMS error); 2) similar
      spatial CA distribution trends across tumor with increased uptake at the tumor
      boundary.

PMID- 22982404
TI  - Early Treg suppression by a listeriolysin-O-expressing E. coli vaccine in
      heterologous prime-boost vaccination against cancer.
AB  - Studies have shown that an enhanced CD8+ T cell response and better tumor
      protection can be achieved by heterologous prime-boost vaccination in mice. Such
      heterologous vaccination can be more immunogenic than the homologous setting. We
      previously demonstrated that a listeriolysin-O (LLO)-expressing E. coli vaccine
      can enhance CD8-cytotoxic T cell (CTL) responses by reducing regulatory T cell
      (Treg)-directed suppression. In the present study, we assessed the combination of
      this approach with plasmid DNA vaccination, in a prime-boost immunization
      strategy. E. coli-LLO bacteria expressing ovalbumin (OVA) and plasmid pcDNA
      encoding OVA were used to vaccinate naive or B16-OVA tumor-bearing C57B6 mice.
      The anticancer activity was measured in a tumor prevention or therapeutic model.
      Higher OVA-specific CD8+ T cell responses and greater tumor inhibition were seen
      in the bacterial-prime/plasmid-boost setting than with the homologous and
      reversed sequences. This tumor protection effect from heterologous prime-boost
      remained in the therapeutic model. When examining the Treg effect during the
      prime-boost immunization, we found that only early Treg-suppression/depletion
      could lead to better antigen-specific CTL and tumor response. Our studies offer
      the first evidence that a listeriolysin-O E. coli vaccine can induce an enhanced
      antitumor effect in conjunction with DNA in a heterologous prime-boost protocol,
      and suggest that early Treg inhibition is crucial to a successful immunization
      against cancer.

PMID- 22982405
TI  - Pro-apoptotic or anti-apoptotic property of X protein of hepatitis B virus is
      determined by phosphorylation at Ser31 by Akt.
AB  - The X protein of hepatitis B virus (HBx) has been specifically implicated in
      either pro-apoptotic or anti-apoptotic activity in an experimental system, but
      the underlying mechanism is yet uncertain. Activations of survival and
      proliferation signaling pathways appear to account partly for its anti-apoptotic
      property. Change in mitochondrial membrane potential may be responsible for its
      apoptotic property. In this study, we isolated two HBx isoforms from an HBV
      carrier, one of which contains Akt phosphorylation site at Ser31 and functions as
      an anti-apoptotic protein (designated HBx-S31). The other does not contain Akt
      phosphorylation site and functions as an apoptotic protein (designated HBx-L31).
      HBx-S31 can activate Akt, whereas HBx-L31 cannot; the former enhances tumor
      growth, whereas the latter suppresses tumorigenesis. Our study provides evidence
      that HBx plays dual roles, namely pro-apoptotic and anti-apoptotic, through
      different isoforms in which HBx with Ser31 transduces survival signal.

PMID- 22982406
TI  - Liposome imaging agents in personalized medicine.
AB  - In recent years the importance of molecular and diagnostic imaging has increased
      dramatically in the treatment planning of many diseases and in particular in
      cancer therapy. Within nanomedicine there are particularly interesting
      possibilities for combining imaging and therapy. Engineered liposomes that
      selectively localize in tumor tissue can transport both drugs and imaging agents,
      which allows for a theranostic approach with great potential in personalized
      medicine. Radiolabeling of liposomes have for many years been used in preclinical
      studies for evaluating liposome in vivo performance and has been an important
      tool in the development of liposomal drugs. However, advanced imaging systems now
      provide new possibilities for non-invasive monitoring of liposome biodistribution
      in humans. Thus, advances in imaging and developments in liposome radiolabeling
      techniques allow us to enter a new arena where we start to consider how to use
      imaging for patient selection and treatment monitoring in connection to
      nanocarrier based medicines. Nanocarrier imaging agents could furthermore have
      interesting properties for disease diagnostics and staging. Here, we review the
      major advances in the development of radiolabeled liposomes for imaging as a tool
      in personalized medicine.

PMID- 22982408
TI  - Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells.
AB  - Exosomes are small extracellular vesicles released to the extracellular milieu
      through fusion of multivesicular bodies with the plasma membrane. These vesicles
      contain microRNAs and might therefore be vehicles transferring genetic
      information between cells. The aim of this study was to investigate whether there
      was a sorting of microRNAs into exosomes in the prostate cancer cell line PC-3.
      In addition, microRNAs in PC-3 cells and in the non-cancerous prostate cell line
      RWPE-1 were compared. Exosomes were isolated from the conditioned media from PC-3
      cells by ultracentrifugation and inspected by electron microscopy. Total RNA was
      isolated and microRNAs were analyzed by microarray analysis and real time RT-PCR.
      MicroRNA microarray analysis revealed that the microRNA profile of PC-3 released
      exosomes was similar to the profile of the corresponding parent cells.
      Nevertheless, a sorting of certain microRNAs into exosomes was observed, and low
      number microRNAs (microRNAs with a low number in their name) were found to be
      underrepresented in these vesicles. Moreover, the miRNA profile of PC-3 cells
      resembled the miRNA profile of RWPE-1 cells, though some miRNAs were found to be
      differently expressed in these cell lines. These results show that exosomes from
      PC-3 cells, in agreement with previous reports from other cell types, contain
      microRNAs. Furthermore, this study supports the idea that there is a sorting of
      microRNAs into exosomes and adds a new perspective by pointing at the
      underrepresentation of low number miRNAs in PC-3 released exosomes.

PMID- 22982409
TI  - Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal
      muscle by hypoxia preconditioning with cobalt chloride.
AB  - High altitude/hypoxia training is known to improve physical performance in
      athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream
      genes that facilitate hypoxia adaptation in muscle to increase physical
      performance. Cobalt chloride (CoCl2), a hypoxia mimetic, stabilizes HIF-1, which
      otherwise is degraded in normoxic conditions. We studied the effects of hypoxia
      preconditioning by CoCl2 supplementation on physical performance, glucose
      metabolism, and mitochondrial biogenesis using rodent model. The results showed
      significant increase in physical performance in cobalt supplemented rats without
      (two times) or with training (3.3 times) as compared to control animals. CoCl2
      supplementation in rats augmented the biological activities of enzymes of TCA
      cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of
      glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by
      aerobic respiration. There was also an increase in mitochondrial biogenesis in
      skeletal muscle observed by increased mRNA expressions of mitochondrial
      biogenesis markers which was further confirmed by electron microscopy. Moreover,
      nitric oxide production increased in skeletal muscle in cobalt supplemented rats,
      which seems to be the major reason for peroxisome proliferator activated receptor
      gamma coactivator-1alpha (PGC-1alpha) induction and mitochondrial biogenesis.
      Thus, in conclusion, we state that hypoxia preconditioning by CoCl2
      supplementation in rats increases mitochondrial biogenesis, glucose uptake and
      metabolism by aerobic respiration in skeletal muscle, which leads to increased
      physical performance. The significance of this study lies in understanding the
      molecular mechanism of hypoxia adaptation and improvement of work performance in
      normal as well as extreme conditions like hypoxia via hypoxia preconditioning.

PMID- 22982407
TI  - The combined effect of acetylation and glycation on the chaperone and anti
      apoptotic functions of human alpha-crystallin.
AB  - N(epsilon)-acetylation occurs on select lysine residues in alpha-crystallin of
      the human lens and alters its chaperone function. In this study, we investigated
      the effect of N(epsilon)-acetylation on advanced glycation end product (AGE)
      formation and consequences of the combined N(epsilon)-acetylation and AGE
      formation on the function of alpha-crystallin. Immunoprecipitation experiments
      revealed that N(epsilon)-acetylation of lysine residues and AGE formation co
      occurs in both alphaA- and alphaB-crystallin of the human lens. Prior acetylation
      of alphaA- and alphaB-crystallin with acetic anhydride (Ac(2)O) before glycation
      with methylglyoxal (MGO) resulted in significant inhibition of the synthesis of
      two AGEs, hydroimidazolone (HI) and argpyrimidine. Similarly, synthesis of
      ascorbate-derived AGEs, pentosidine and N(epsilon)-carboxymethyl lysine (CML),
      was inhibited in both proteins by prior acetylation. In all cases, inhibition of
      AGE synthesis was positively related to the degree of acetylation. While prior
      acetylation further increased the chaperone activity of MGO-glycated alphaA
      crystallin, it inhibited the loss of chaperone activity by ascorbate-glycation in
      both proteins. BioPORTER-mediated transfer of alphaA- and alphaB-crystallin into
      CHO cells resulted in significant protection against hyperthermia-induced
      apoptosis. This effect was enhanced in acetylated and MGO-modified alphaA- and
      alphaB-crystallin. Caspase-3 activity was reduced in alpha-crystallin transferred
      cells. Glycation of acetylated proteins with either MGO or ascorbate produced no
      significant change in the anti-apoptotic function. Collectively, these data
      demonstrate that lysine acetylation and AGE formation can occur concurrently in
      alpha-crystallin of human lens, and that lysine acetylation improves anti
      apoptotic function of alpha-crystallin and prevents ascorbate-mediated loss of
      chaperone function.

PMID- 22982410
TI  - Association between apolipoprotein E gene polymorphism and the risk of multiple
      sclerosis: a meta-analysis of 6977 subjects.
AB  - Epidemiological studies have evaluated the association between apolipoprotein E
      (ApoE) gene polymorphism and multiple sclerosis (MS) risk. However, the results
      remain conflicting. Therefore, in order to derive a more precise association of
      ApoE gene polymorphism with MS risk, we performed this meta-analysis. Systematic
      searches of electronic databases PubMed, Embase and Web of Science, as well as
      hand searching of the references of identified articles were performed. Twenty
      studies were identified, covering a total of 4080 MS cases and 2897 controls. The
      results showed evidence for significant association between ApoE epsilon2
      mutation and MS risk (for epsilon2/epsilon4 versus epsilon3/epsilon3: OR=1.74,
      95% CI=1.12-2.71, p=0.01; for epsilon2 allele versus epsilon3 allele: OR=1.16,
      95% CI=1.01-1.35, p=0.04). In the subgroup analysis by ethnicity, the similar
      results were obtained among Europeans (for epsilon2/epsilon4 versus
      epsilon3/epsilon3: OR=1.81, 95% CI=1.14-2.87, p=0.01; for epsilon2 allele versus
      epsilon3 allele: OR=1.19, 95% CI=1.02-1.38, p=0.03). After excluding the outlier
      studies by observing Galbraith plot, marginal association was found between ApoE
      epsilon3/epsilon4 genotype and the protective factor for MS (for
      epsilon3/epsilon4 versus epsilon3/epsilon3: OR=0.86, 95% CI=0.75-0.99, p=0.04).
      In summary, the present meta-analysis provides evidence that ApoE epsilon2
      mutation is associated with MS risk. In addition, ApoE epsilon3/epsilon4 genotype
      appears to be a protective factor for MS.

PMID- 22982411
TI  - No association between MTHFR C677T polymorphism and completed suicide.
AB  - MTHFR C677T polymorphism (rs1801133) was associated with numerous psychiatric
      conditions but no prior study investigated whether it predisposes to completed
      suicide. We typed rs1801133 in 692 suicide victims and 3257 controls
      representative of a Polish adult population (the WOBASZ cohort). Although we had
      a power of 0.8 to detect (at alpha 0.05) an allelic OR=1.19, we did not find
      significant difference among suicides vs. controls in the prevalence of the MTHFR
      677T allele (OR=1.02, p=0.759) or the TT genotype (OR=1.01, p=0.926). Since among
      controls we found an association between TT and depression defined by Beck
      Depression Inventory (BDI, OR=1.61, p=0.049) we also compared suicides with
      controls without signs of depression (BDI <= 11) but found no association
      (OR=1.0, p=0.976). Analyses within suicides showed trends (not significant after
      Bonferroni correction) for correlations between the dose of the T allele and age
      at death among males and blood ethanol concentration among females, who committed
      suicide under the influence of alcohol. We conclude that MTHFR C677T polymorphism
      is not a risk factor for completed suicide. The sex-specific trends for
      correlations between rs1801133 and age at death, and blood ethanol concentration
      should be studied further.

PMID- 22982412
TI  - Sense transcripts originated from an internal part of the human retrotransposon
      LINE-1 5' UTR.
AB  - L1 (LINE-1) is one of the most abundant families of human transposable elements.
      Full-length human L1 has an ~900 bp long 5' untranslated region (5' UTR) which
      harbors an internal promoter for the RNA polymerase II. It is generally accepted
      that the first 100 bp of the 5' UTR function as a "minimal promoter" which
      directs transcription of the entire LINE-1 unit from the extreme 5' terminus. We
      re-investigated promoter activities of the different DNA fragments that cover the
      whole L1 5' UTR in cultured human cells by using the luciferase reporter system.
      Analysis of both mRNA expression and luciferase activity levels indicated that
      the very important region for the effective transcription is located within the
      internal part of the L1 5' UTR between nucleotide positions +390 and +526. 5'
      RACE analysis revealed that in the context of the complete 5' UTR, this part
      drives mRNA synthesis both from the canonical 5'-terminal transcription start
      site (TSS) and from within the internal region. In the absence of the first 100
      bp, the L1 5' UTR efficiently directed transcription from aberrant TSSs located
      within its 3' proximal part or the ORF1. Finally, we analyzed transcripts
      originated from endogenous (genomic) L1 elements and identified two novel TSSs
      located at positions +525 and +570. We propose a model in which the internal part
      (390-526) of the L1 5' UTR plays a key role for recruitment of transcription
      initiation complex, which then may be either positioned onto the 5' terminally
      located "minimal promoter", or used proximately to direct 5' truncated RNA copy.
      Intriguingly, this internal regulatory element substantially overlaps with the
      region of the L1 5' UTR that is known to drive transcription in the opposite
      direction suggesting the existence of a common core for the bidirectional
      transcription.

PMID- 22982413
TI  - The role of chemokine and chemokine receptor gene variants on the susceptibility
      and clinicopathological characteristics of bladder cancer.
AB  - The gene variants of the chemokine and chemokine receptor genes associated with
      inflammation may be involved in cancer initiation and progression. The aim of
      this study was to explore the possible association of monocyte chemoattractant
      protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3'A and chemokine
      receptors CCR2A V64I, CCR5 Delta32, CCR5 59029 and CXCR4 gene polymorphisms with
      the risk and clinicopathological characteristics of bladder cancer (BC) in a
      Turkish population. The genotyping was done by PCR and PCR-Restriction Fragment
      Length Polymorphism (RFLP) methods in 142 histologically confirmed BC patients
      and 197 controls. The SDF-1 3'AA genotype conferred significantly increased
      susceptibility to BC. The carriers with AA genotype or at least one A allele of
      CCR2 had an increased risk of developing BC. CCR5 wt/Delta32 genotype and CCR5
      Delta32 allele were also observed to be involved in the susceptibility to BC.
      Additionally, the combination of CCR2 V64I and CCR5 Delta32 (i.e., GG-wt/Delta32)
      was found to be associated with BC risk. With respect to the stage of BC, the AA
      genotype of SDF-1 and at least one T allele of CXCR4 were significantly
      associated with high T stage as compared to GG genotype of SDF-1 and CC genotype
      of CXCR4. Furthermore, BC patients with AA genotype or at least one A allele of
      CCR2 had an increased risk of high grade and stage tumors as compared to those
      with GG genotype. Our results suggest that the genetic variants of SDF-1 3'A,
      CCR2A V64I and CCR5 Delta32 gene polymorphisms may modify the BC risk.
      Furthermore, SDF-1 3'A, CCR2A V64I and CXCR4 gene polymorphisms may contribute to
      the muscle invasive BC in a Turkish population.

PMID- 22982414
TI  - Meta-analysis on association between the ATP-binding cassette transporter A1 gene
      (ABCA1) and Alzheimer's disease.
AB  - PURPOSE: In the past decade, a number of case-control studies have been carried
      out to investigate the relationship between ABCA1 polymorphisms and Alzheimer's
      disease (AD). However, these studies have yielded contradictory results. To
      investigate this inconsistency, a meta-analysis was performed. METHODS: Databases
      including PubMed, Web of Science, EMBASE and CNKI were searched to find relevant
      studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      assess the strength of association. RESULTS: A total of 13 case-control studies,
      involving 6214 patients and 6034 controls for ABCA1 polymorphisms were included.
      In a combined analysis, the summary per-allele odds ratio for AD of the 219K was
      1.03 (95% CI: 0.93-1.14, p=0.56). A meta-analysis of studies on the 883M and
      1587K variant showed no significant overall association with AD, yielding a per
      allele odds ratio of 1.10 (95% CI: 0.96-1.26, p=0.16), and 1.09 (95% CI: 0.97
      1.24, p=0.16) respectively. Similar results were also found for heterozygous and
      homozygous. In the subgroup analysis by ethnicity, sample size, APOE status and
      onset type, no significant associations were found in almost all genetic models.
      CONCLUSIONS: In summary, there was no significant association detected between
      ABCA1 R219K, I883M and R1587K polymorphisms and risk for AD.

PMID- 22982415
TI  - Transrepression activity of T-box1 in a gene regulation network in mouse cells.
AB  - T-box1 (TBX1) has been identified as a candidate disease-causing gene in DiGeorge
      syndrome/conotruncal anomaly face syndrome (DGS/CAFS). Tbx1 can function as a
      transcriptional transactivator as well as a transrepressor. Although the
      transactivating role of Tbx1 has been the focus of a number of published studies,
      its transrepression activity has been largely unexplored. Thus, this study
      centers on the identification of potential transrepressed targets of Tbx1. By
      subtractive hybridization, we compared the expression profiles of control mouse
      P19 cells and P19 cells depleted of Tbx1 via RNA interference. We identified 127
      genes that were potentially transrepressed by Tbx1. Of the transrepressed genes,
      we focused on Ywhae and C1qbp and carried out promoter assays. The results showed
      that Tbx1 potentially transrepresses the promoter activities of these genes via
      palindromic sequences, including 5'-CCACAG-3' and 5'-(C/G)TGTG(C/G)-3', harbored
      within the promoters. Electromobility shift assays also showed that Tbx1
      specifically interacts with certain portions of these promoter sequences.
      Moreover, the construction of Tbx1 mutants containing known human TBX1 mutations
      showed that these mutations result in the loss of Tbx1 transrepression activity.
      These results indicate that Tbx1 functions as a transrepressor in a gene
      regulation network, wherein Ywhae and C1qbp are 2 of the targets transrepressed
      by Tbx1 via T-box binding elements. Hence, the loss of TBX1 transrepression
      activity could be associated with the disease phenotypes of patients with
      DGS/CAFS.

PMID- 22982416
TI  - Promoter polymorphisms in DNA repair gene ERCC5 and susceptibility to gastric
      cancer in Chinese.
AB  - Genetic variations in excision repair cross-complementing group 5 (ERCC5) might
      influence individual vulnerability to gastric cancer (GC). We investigated
      effects of two putatively functional polymorphisms in ERCC5 promoter region,
      rs751402 (+25A>G) and rs2296147 (+202C>T), and their potential interaction with
      environment factors on the risk of developing GC. We performed a sex- and age
      matched case-control design with 400 GC cases and 400 healthy controls for
      rs751402 and 403 GC cases and 403 healthy controls for rs2296147. Our results
      showed that rs751402 were associated with increased GC risk (AA vs. GG: OR=1.99,
      95%CI: 1.20-3.31, P=0.008; AG+AA vs. GG: OR=1.41, 95%CI: 1.07-1.86, P=0.016), and
      rs2296147 was also associated with increased cancer risk (CC vs. TT: OR=2.17,
      95%CI: 1.04-4.54, P=0.039; CC vs. CT+TT: OR=2.26, 95%CI: 1.09-4.69, P=0.028). In
      a stratified analysis, rs751402 (AG+AA vs. GG: OR=1.44, 95%CI: 1.02-2.02,
      P=0.037) and rs2296147 (CC vs. CT+TT: OR=2.33, 95%CI: 1.00-5.44, P=0.050) were
      also found to be associated with diffuse-type GC risk. The most common GT
      haplotype (rs751402-rs2296147) showed protective effect for GC development
      (OR=0.73, 95%CI: 0.58-0.91, P=0.005), and especially for diffuse-type GC
      (OR=0.68, 95%CI: 0.52-0.90, P=0.006). Genetic effects on increased GC risk seemed
      to be enhanced by Helicobacter pylori infection, smoking and alcohol drinking,
      with corresponding adjusted ORs of 4.57, 2.42 and 2.50 for the rs751402 AG/AA
      variants, and of 5.32, 3.20 and 6.87 for the rs2296147 CC variant, but their
      interaction effects on GC risk didn't reach statistically significance. ERCC5
      rs751402 and rs2296147 polymorphisms might alter the risk of developing GC and
      especially the diffuse subtype. Further validation of our results in larger
      populations and additional studies evaluating their function impact are required.

PMID- 22982417
TI  - Impaired c-src activation and motility defects in PEA3-null fibroblasts.
AB  - Null mutations in the pea3 allele compromise the capacity of mammary tumors to
      metastasize in MMTV-Neu/ErbB2/HER2 transgenic mice, indicating a motility defect
      in PEA3-null cells. Cellular and biochemical analyses of established PEA3-null
      fibroblasts show impaired motility and aberrant localization of adhesion proteins
      in spreading cells. Our results show that PEA3-/- cells express normal levels of
      key adhesion components, but that spreading PEA3-null cells fail to activate c
      src and to downregulate phospho-FAK(Y397), suggesting that focal adhesion
      signaling is impaired. Supporting this, biochemical analysis revealed that
      adhesion complex-associated proteins such as p130Cas failed to undergo tyrosine
      phosphorylation and dissociated from the adhesion complex with delayed kinetics.
      Overall our data show that the motility defects observed in PEA3-null cells are
      due to altered adhesion signaling.

PMID- 22982418
TI  - Modulation of TRPV1-dependent contractility of normal and diabetic bladder smooth
      muscle by analgesic toxins from sea anemone Heteractis crispa.
AB  - AIMS: TRPV1-expressing, capsaicin (CAP)-sensitive afferent fibers innervating
      bladder in addition to sensory function also exhibit "efferent" features
      consisting in TRPV1-dependent release of tachykinins (TAC) affecting detrusor
      smooth muscle (DSM) contractions. Our aim was to investigate the effects of two
      novel polypeptide inhibitors of TRPV1 from the venom of tropical sea anemone
      Heteractis crispa, APHC1 and APHC3, on the contractions of DSM from bladders of
      normal and diabetic rats. MAIN METHODS: Experiments were conducted on urothelium
      devoid DSM strips from normal rats and rats 8weeks after streptozotocin-induced
      diabetes by means of contraction force measurements. KEY FINDINGS: Pre-exposure
      of DSM strips to APHC1 or APHC3 (200nM) specifically inhibited CAP-induced, TRPV1
      dependent contractions. Both peptides also transiently enhanced basal tone and
      spontaneous contractions of DSM strips followed by delayed suppression of
      electric field stimulation (EFS)-evoked nonadrenergic-noncholinergic (NANC)
      contractions. The decrease of the amplitude of EFS-evoked NANC contractions by
      ARNS1 or ARNS3 reached 38.5+/-3.4% and 25.1+/-1.6%, respectively, in normal DSM
      strips and 46.3+/-3.3% and 43.9+/-1.8%, respectively, in diabetic ones. APHC
      peptide-induced transient enhancement of basal tone could be mimicked by serine
      protease inhibitor, 4-(2-aminoethyl)bezenesulfonyl fluoride (300 MUM).
      SIGNIFICANCE: Our results demonstrate that ARNS1 and ARNS3 may be considered as
      effective inhibitors of bladder contractility especially during diabetic
      cystopathy. Modality of action of APHC-polypeptides via the mechanisms involving
      decreased TRPV1-dependent release of TAC from bladder afferents and suppression
      of TAC degradation due to their activity as endogenous proteases inhibitors is
      proposed.

PMID- 22982419
TI  - The effect of intrathecal gabapentin on neuropathic pain is independent of the
      integrity of the dorsolateral funiculus in rats.
AB  - AIM: This study evaluates the contribution of inhibitory pain pathways that
      descend to the spinal cord through the dorsolateral funiculus (DLF) on the effect
      of intrathecal gabapentin against spinal nerve ligation (SNL)-induced behavioral
      hypersensitivity to mechanical stimulation in rats. MAIN METHOD: Rats were
      submitted to a sham or complete ligation of the right L5 and L6 spinal nerves and
      a sham or complete DLF lesion. Next, the changes induced by intrathecal
      administration of gabapentin on the paw withdrawal threshold of rats to
      mechanical stimulation were evaluated electronically. KEY FINDINGS: Intrathecal
      gabapentin (200MUg/5MUl) that was injected 2 or 7days after surgery fully
      inhibited the SNL-induced behavioral hypersensitivity to mechanical stimulation
      in sham DLF-lesioned rats; gabapentin was effective against the SNL-induced
      behavioral hypersensitivity to mechanical stimulation also in DLF-lesioned rats.
      SIGNIFICANCE: The effect of intrathecally administered gabapentin against SNL
      induced behavioral hypersensitivity to mechanical stimulation in rats does not
      depend on the activation of nerve fibers that descend to the spinal cord via the
      DLF.

PMID- 22982420
TI  - Axial compression of a hollow cylinder filled with foam: a study of porcupine
      quills.
AB  - Porcupines use their lightweight quills, which are strong enough to support
      significant compression and flexure loads, for defense. Hystrix, with long and
      thick quills, belongs to the family of Hystricidae (Old World porcupines), while
      Erethizon, with smaller quills, belongs to the Erethizontidae family (New World
      porcupines). The objective of this work is to compare the structure and
      compressive properties of quills from Hystrix and Erethizon. Both quills have a
      thin keratinous cortex filled with closed-cell foam that has cell diameters
      decreasing from the center to the cortex. Hystrix quills have stiffeners that
      extend from the cortex towards the center. The local buckling strength is larger
      for Hystrix, and very good agreement is found between the predicted values and
      the experimental ones for both quills. The foam shows extensive deformation, both
      tensile and compressive, around the buckled cortex.

PMID- 22982421
TI  - Prospective evaluation and classification of ureteral wall injuries resulting
      from insertion of a ureteral access sheath during retrograde intrarenal surgery.
AB  - PURPOSE: The safety of using a ureteral access sheath during retrograde
      intrarenal surgery remains controversial. Using a novel classification, we
      prospectively evaluated the incidence and severity of ureteral access sheath
      driven ureteral wall injury after flexible ureteroscopy for retrograde intrarenal
      surgery. MATERIALS AND METHODS: Data on a total of 359 consecutive patients who
      underwent retrograde intrarenal surgery for kidney stone were prospectively
      collected at 2 academic centers. We propose what is to our knowledge a novel
      endoscopic classification of iatrogenic ureteral wall injury. Ureteral injuries
      after retrograde intrarenal surgery were assessed visually with a digital
      flexible ureterorenoscope. The primary outcome measure was the incidence and
      nature of ureteral injuries. We sought factors predisposing to such injuries.
      RESULTS: Ureteral wall injury was found in 167 patients (46.5%). Severe injury
      involving the smooth muscle layers was observed in 48 patients (13.3%). Males vs
      females (p = 0.024) and older vs younger patients (p = 0.018) were at higher risk
      for severe ureteral access sheath related ureteral injury. The most significant
      predictor of severe injury was absent ureteral Double-J(r) stenting before
      retrograde intrarenal surgery (p <0.0001). Pre-stenting vs no pre-stenting
      decreased the risk of severe injury by sevenfold. Body mass index, a history of
      diabetes mellitus, vascular disease or abdominopelvic radiation therapy and
      operative time were not associated with severe ureteral injury. CONCLUSIONS:
      Ureteral access sheath use for retrograde intrarenal surgery should involve
      systematic visual assessment of the entire ureter to recognize severe ureteral
      injury. The incidence of severe ureteral injury is largely decreased by
      preoperative Double-J stenting.

PMID- 22982422
TI  - Prophylactic effect of tadalafil on bladder function in a rat model of chronic
      bladder ischemia.
AB  - PURPOSE: We investigated the effect of tadalafil on chronic ischemia related
      bladder dysfunction. MATERIALS AND METHODS: Adult male Sprague-Dawley(r) rats
      were divided into control, arterial endothelial injury and arterial endothelial
      injury with tadalafil treatment groups. The arterial injury and arterial injury
      tadalafil groups underwent endothelial injury of the iliac arteries and received
      a 2% cholesterol diet after injury. Arterial injury-tadalafil rats received
      tadalafil (2 mg/kg per day) orally for 8 weeks after injury. The control group
      received a regular diet. At 8 weeks urodynamic investigation was performed.
      Bladder tissue was harvested for pharmacological studies, and histological
      examination of the iliac arteries and bladders was performed. RESULTS: Iliac
      arteries from arterial injury and arterial injury-tadalafil rats showed
      neointimal formation and luminal occlusion. In the arterial injury group the
      micturition interval was significantly shorter (mean +/- SEM 5.4 +/- 0.5 vs 11.1
      +/- 1.1 minutes), and bladder capacity and voided volume were less than in
      controls. Contractile responses of bladder strips to KCl, electrical field
      stimulation and carbachol were significantly less after arterial injury than in
      controls. The arterial injury group showed a significantly increased percent of
      collagen compared with controls (mean 37.4% +/- 1.8% vs 21.5% +/- 1.8%). In the
      arterial injury-tadalafil group intimal formation and luminal occlusion were not
      prevented. However, there were significant improvements in all functional and
      morphological parameters compared with the arterial injury group. CONCLUSIONS:
      Arterial occlusive disease may lead to chronic bladder ischemia and bladder
      hyperactivity. Chronic treatment with tadalafil protects bladder function and
      morphology, resulting in decreased bladder hyperactivity. If valid for humans,
      the data support phosphodiesterase 5 inhibition as treatment for chronic ischemia
      related bladder dysfunction.

PMID- 22982423
TI  - Development of diurnal micturition pattern in mice after weaning.
AB  - PURPOSE: The development of micturition in mice has been poorly studied because
      of the minute urine volume voided per micturition. We characterized development
      of the micturition pattern in young mice. MATERIALS AND METHODS: Micturition in
      young and adult C57BL/6 strain mice, including 5 males and 4 females at age 3
      weeks immediately after weaning, and 5 of each gender at ages 9 to 10 weeks,
      respectively, was recorded by the automated voided stain on paper method.
      Micturition data were obtained under 12-hour light/dark cycles in young mice for
      16 days and in adult mice for 4 days. Diurnal variations were assessed during 8
      hours until the first void after lights off and those until lights on. The 24
      hour rhythmicity of urinary frequency was calculated for 4-day data at the
      beginning and at the end on young mice, and for 4-day data on adult mice using a
      chi-square periodogram and relative power spectral density. RESULTS: Mean
      frequency was 20 to 30 times per day. Total daily urine volume and mean daily
      urine volume voided per micturition increased with age. The diurnal rhythm of
      frequency matured to adult levels with development, which was primarily achieved
      by maturation of the diurnal variation of urine volume in male mice, followed by
      female mice. Diurnal variation of urine volume voided per micturition was
      indistinct at the initial stage and gradually matured toward adult levels.
      CONCLUSIONS: The automated voided stain on paper method was used to record
      micturition development in young mice. This generated data corresponding to
      frequency-volume charts in humans. Our findings could lead to the establishment
      of a mouse model of developmental micturition disorders, such as nocturnal
      enuresis.

PMID- 22982424
TI  - Prebiopsy magnetic resonance imaging and prostate cancer detection: comparison of
      random and targeted biopsies.
AB  - PURPOSE: We compared the accuracy of visual targeted biopsies vs computerized
      transrectal ultrasound-magnetic resonance imaging registration using a rigid
      (Esaote(r), nondeformable) or elastic (Koelis(r), deformable) approach. MATERIALS
      AND METHODS: A total of 391 consecutive patients with suspected localized
      prostate cancer were prospectively included in analysis. All patients underwent
      prostate magnetic resonance imaging, followed by 10 to 12-core random prostate
      biopsies. When magnetic resonance imaging detected suspicious findings, targeted
      biopsy was performed, including visual, rigid system and elastic system targeted
      biopsies in the first 127 patients, the next 131 and the last 133, respectively.
      Cancer detection rates were assessed by conditional logistic regression. Targeted
      biopsies alone and random biopsies were further compared for the amount of tissue
      sampled and microfocal cancer detection, the latter defined as a single core with
      5 mm or less of Gleason 6 cancer. RESULTS: Patient characteristics and random
      biopsy detection rates were similar among the groups. Magnetic resonance imaging
      detected at least 1 suspicious area in 54 (42%), 78 (59%) and 82 patients (62%)
      in groups 1, 2 and 3, respectively. The cancer detection rates of rigid and
      elastic system targeted biopsies were significantly higher than the random biopsy
      rate (p = 0.0065 and 0.0016, respectively). Visual targeted biopsy did not
      perform better than random biopsy (p = 0.66). Rigid and elastic system targeted
      biopsies allowed for decreasing the number of cores and the detection of
      microfocal cancer, while increasing the detection of high grade cancer.
      CONCLUSIONS: When performed with computerized magnetic resonance imaging
      transrectal ultrasound image registration, targeted biopsy alone improved cancer
      detection over random biopsies, decreased the detection rate of microfocal cancer
      and increased the detection rate of cancer with a Gleason score of greater than
      6.

PMID- 22982426
TI  - Reduction in hospital admission rates due to post-prostate biopsy infections
      after augmenting standard antibiotic prophylaxis.
AB  - PURPOSE: We evaluated the incidence of infectious complications requiring
      hospitalization after transrectal ultrasound guided prostate biopsy, comparing an
      augmented regimen of antibiotic prophylaxis to the standard regimen, and
      established cost-effectiveness at our center. MATERIALS AND METHODS: Our standard
      antibiotic prophylaxis regimen consisted of 3 days of ciprofloxacin or BactrimTM
      DS in the perioperative period. An increase in hospital admissions related to
      infection after transrectal ultrasound guided biopsy from January 2010 through
      December 2010 led us to initiate an augmented regimen of 3 days of ciprofloxacin
      or Bactrim DS in addition to 1 dose of intramuscular gentamicin before biopsy
      from January 2011 to December 2011. Urine and blood cultures along with bacterial
      susceptibilities were obtained at admission and compared between the 2 groups.
      Cost analysis was done to determine the cost-effectiveness of standard and
      augmented regimens. RESULTS: The rate of hospitalization due to post-biopsy
      infections was 3.8% (11 patients among 290 biopsies) in 2010, which decreased to
      0.6% (2 patients among 310 biopsies) in 2011 (p <0.001). Of the admitted patients
      who received standard prophylaxis, 73% had fluoroquinolone resistant Escherichia
      coli urinary infection and/or bacteremia and only 9% had strains resistant to
      gentamicin. Multivariate analysis showed that the standard regimen was
      significantly associated with hospital admission due to post-biopsy infection (HR
      2.078 +/- 0.84, p = 0.013). The augmented regimen resulted in a cost savings of
      $15,700 per 100 patients compared to the standard regimen. CONCLUSIONS: The
      addition of gentamicin to current prophylactic regimens significantly reduced the
      rate of hospitalization for post-biopsy infectious complications and was shown to
      be cost-effective.

PMID- 22982425
TI  - The effect of urodynamic testing on clinical diagnosis, treatment plan and
      outcomes in women undergoing stress urinary incontinence surgery.
AB  - PURPOSE: We evaluated the influence of preoperative urodynamic studies on
      diagnoses, global treatment plans and outcomes in women treated with surgery for
      uncomplicated stress predominant urinary incontinence. MATERIALS AND METHODS: We
      performed a secondary analysis from a multicenter, randomized trial of the value
      of preoperative urodynamic studies. Physicians provided diagnoses before and
      after urodynamic studies and global treatment plans, defined as proceeding with
      surgery, surgery type, surgical modification and nonoperative therapy. Treatment
      plan changes and surgical outcomes between office evaluation and office
      evaluation plus urodynamic studies were compared by the McNemar test. RESULTS: Of
      315 subjects randomized to urodynamic studies after office evaluation 294 had
      evaluable data. Urodynamic studies changed the office evaluation diagnoses in 167
      women (56.8%), decreasing the diagnoses of overactive bladder-wet (41.6% to
      25.2%, p <0.001), overactive bladder-dry (31.4% to 20.8%, p = 0.002) and
      intrinsic sphincter deficiency (19.4% to 12.6%, p = 0.003) but increasing the
      diagnosis of voiding dysfunction (2.2% to 11.9%, p <0.001). After urodynamic
      studies physicians canceled surgery in 4 of 294 women (1.4%), changed the
      incontinence procedure in 13 (4.4%) and planned to modify mid urethral sling
      tension (more or less obstructive) in 20 women (6.8%). Nonoperative treatment
      plans changed in 40 of 294 women (14%). Urodynamic study driven treatment plan
      changes were not associated with treatment success (OR 0.96, 95% CI 0.41, 2.25, p
      = 0.92) but they were associated with increased postoperative treatment for urge
      urinary incontinence (OR 3.23, 95% CI 1.46, 7.14, p = 0.004). CONCLUSIONS:
      Urodynamic studies significantly changed clinical diagnoses but infrequently
      changed the global treatment plan or influenced surgeon decision to cancel,
      change or modify surgical plans. Global treatment plan changes were associated
      with increased treatment for postoperative urgency urinary incontinence.

PMID- 22982427
TI  - Is there a role of the enhancement degree of the lesion on computerized
      tomography for the characterization of renal tumors?
AB  - PURPOSE: We determined the role of tumor enhancement on dynamic enhanced
      computerized tomography for differentiating pathological characteristics.
      MATERIALS AND METHODS: A total of 149 patients with renal tumor underwent dynamic
      enhanced computerized tomography at our university from June 2007 to November
      2011. Tumors were treated surgically and pathological evaluation was done.
      Precontrast and postcontrast HU values, and the difference were recorded.
      Postcontrast HU evaluations were done at the nephrographic phase of the
      procedure. Tumor HU values were compared according to histological subtype, tumor
      grade and pathological stage. RESULTS: Mean +/- SD patient age was 57 +/- 13
      years and mean tumor size was 4.8 +/- 2.7 cm. Postcontrast HU and contrast
      difference values were significantly lower in the malignant group. A cutoff HU
      value of 138 HU (mean AUC 0.893 +/- 0.027, 95% CI 0.84-0.94) differentiated renal
      cell cancer from oncocytoma with 88% sensitivity and 87% specificity. Low and
      high grade cases demonstrated similar precontrast and postcontrast HU, and
      contrast difference values. These enhancement parameters were significantly lower
      for higher stage (pT2-3) renal cell cancer than for pT1. We detected higher
      postcontrast values (mean 62 +/- 14 vs 56 +/- 39 HU, p = 0.011) and contrast
      difference values (mean 92 +/- 15 vs 82 +/- 42 HU, p = 0.034) for high grade than
      for low grade renal cell cancer in patients with tumors 4 cm or less.
      CONCLUSIONS: The degree of enhancement on computerized tomography helps
      differentiate tumor characteristics. These outcomes may help the clinician with
      prognostic evaluation and may augment the role of computerized tomography in
      therapeutic planning.

PMID- 22982428
TI  - Effect of the American Urological Association Annual Review course on the results
      of the urology qualifying examination.
AB  - PURPOSE: In this study we assess the impact of a urology dedicated review course
      on the scores of the corresponding board qualifying examination for attendees of
      the urology review course. MATERIALS AND METHODS: The ABU (American Board of
      Urology) Qualifying Examination scores from 2009, 2010 and 2011 were categorized
      into group 1 candidates who attended the AUA (American Urological Association)
      Annual Review Course the same year, and group 2 candidates who did not attend the
      AUA Annual Review Course that same year, and were compared. The scores of the
      preceding year's In-Service Examination were also compared for the same groups of
      candidates and compared to their subsequent first time taken Qualifying
      Examination scores. RESULTS: There was no difference in Qualifying Examination
      scores of resident candidates attending vs not attending the AUA Annual Review
      Course in all 3 years. The overall failure rate was low, and essentially the same
      for all candidates in all years regardless of attendance at the AUA Annual Review
      Course at 2% in 2009, 2% in 2010 and 4% in 2011. Of group 1 candidates the
      majority (80% to 98%) considered the Annual Review Course helpful or very helpful
      in preparation for the Qualifying Examination. CONCLUSIONS: The majority of
      candidates are adequately prepared to pass their Qualifying Examination at the
      conclusion of their residency training program regardless of their attendance of
      the AUA Annual Review Course. This course may help bolster the confidence of the
      candidate preparing for their Qualifying Examination.

PMID- 22982429
TI  - Molecular analysis of erection regulatory factors in sickle cell disease
      associated priapism in the human penis.
AB  - PURPOSE: Priapism is a vasculopathy that occurs in approximately 40% of patients
      with sickle cell disease. Mouse models suggest that dysregulated nitric oxide
      synthase and RhoA/ROCK signaling as well as increased oxidative stress may
      contribute to the mechanisms of sickle cell disease associated priapism. We
      examined changes in the protein expression of nitric oxide synthase and ROCK
      signaling pathways, and a source of oxidative stress, NADPH oxidase, in penile
      erectile tissue from patients with a priapism history etiologically related and
      unrelated to sickle cell disease. MATERIALS AND METHODS: Human penile erectile
      tissue was obtained from 5 patients with sickle cell disease associated priapism
      and from 6 with priapism of other etiologies during nonemergent penile prosthesis
      surgery for erectile dysfunction or priapism management and urethroplasty. Tissue
      was also obtained from 5 control patients without a priapism history during
      penectomy for penile cancer. Samples were collected, immediately placed in cold
      buffer and then frozen in liquid nitrogen. The expression of phosphodiesterase 5,
      endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible
      nitric oxide synthase, RhoA, ROCK1, ROCK2, p47(phox), p67(phox), gp91(phox) and
      beta-actin were determined by Western blot analysis. Nitric oxide was measured
      using the Griess reaction. RESULTS: In the sickle cell disease group
      phosphodiesterase 5 (p <0.05), endothelial nitric oxide synthase (p <0.01) and
      RhoA (p <0.01) expression was significantly decreased, while gp91(phox)
      expression (p <0.05) was significantly increased compared to control values. In
      the nonsickle cell disease group endothelial nitric oxide synthase, ROCK1 and
      p47(phox) expression (each p <0.05) was significantly decreased compared to
      control values. Total nitric oxide levels were not significantly different
      between the study groups. CONCLUSIONS: Mechanisms of sickle cell disease
      associated priapism in the human penis may involve dysfunctional nitric oxide
      synthase and ROCK signaling, and increased oxidative stress associated with NADPH
      oxidase mediated signaling.

PMID- 22982430
TI  - Urodynamic testing--is it a useful tool in the management of children with
      cutaneous stigmata of occult spinal dysraphism?
AB  - PURPOSE: Lumbar cutaneous stigmata in infants may be associated with occult
      spinal dysraphism and often prompt urological evaluation, including urodynamic
      testing. We examined whether urodynamic testing is useful in this population by
      evaluating the association between abnormal urodynamic test results and need for
      tethered cord release. MATERIALS AND METHODS: We reviewed a historical cohort of
      children with cutaneous stigmata of spinal dysraphism referred to our hospital
      from 2002 to 2010. We evaluated patient characteristics, imaging, urodynamic
      studies and neurosurgical interventions. We analyzed the association between
      urodynamic testing and imaging studies, and neurosurgical intervention. RESULTS:
      We retrospectively studied 123 patients with a median age of 11 months (IQR 6.5
      15.5), including 112 nontoilet trained infants (91%). Of the patients 19% (23 of
      123) had abnormal urodynamics, 85% (99 of 116) had abnormal spinal magnetic
      resonance imaging and 96% (98 of 102) had an abnormal spinal ultrasound. Tethered
      cord release was performed in 40 of 121 patients (33%). A significant association
      was found between abnormal urodynamics and neurosurgical intervention (p =
      0.002). Abnormal spinal magnetic resonance imaging was also significantly
      associated with operative intervention (p = 0.05). Ultrasound of the spine (p =
      1.0), ultrasound of the abdomen/pelvis (p = 0.68), history of urinary tract
      infections (p = 1.0) and constipation (p = 0.67) were not associated with
      intervention for tethered cord release. CONCLUSIONS: Abnormal urodynamic studies
      in infants with cutaneous stigmata of spinal dysraphism are significantly
      associated with the requirement for neurosurgical intervention. Urodynamics are
      an important diagnostic modality aiding the neurosurgeon in determining the need
      for surgical intervention in this population.

PMID- 22982431
TI  - Multisystem neuroprosthetic training improves bladder function after severe
      spinal cord injury.
AB  - Severe spinal cord injury leads to neurogenic bladder dysfunction. We recently
      developed a multisystem neuroprosthetic training program that promotes plastic
      changes capable of restoring refined locomotion in rats with severe spinal cord
      injury. We investigated whether multisystem neuroprosthetic training would
      influence the development of posttraumatic bladder dysfunction. MATERIALS AND
      METHODS: Eight and 4 adult rats were randomly assigned to a spinal cord injury
      and an intact control group, respectively. Spinal cord injury consisted of 2
      opposite lateral hemisections (T7 and T11), thus, interrupting all direct
      supraspinal input. After spinal cord injury 4 rats were subjected to a
      multisystem neuroprosthetic training program and 4 were not trained. At 8 weeks
      we performed urodynamics and evaluated kidney function using creatinine and
      cystatin C. Bladder investigation included morphological, histological and
      immunohistochemical evaluations. RESULTS: Bladder capacity increased threefold in
      trained and sevenfold in nontrained rats compared to intact rats. During filling
      we found a mean +/- SEM of 2.7 +/- 1.1 vs 12.6 +/- 5.2 nonvoiding contractions in
      trained vs nontrained rats. Bladder morphology was similar in trained and intact
      rats. Nontrained rats showed detrusor hypertrophy, characterized by increased
      detrusor thickness and a decreased connective tissue-to-smooth muscle ratio. As
      labeled with protein gene product 9.5, general nerve density was significantly
      increased in trained and significantly decreased in nontrained rats. The relative
      proportion of neurofilament 200 positive afferent nerves was significantly lower
      in trained than in intact and nontrained rats. Neuropeptide Y positive fibers
      showed significantly lower density in nontrained rats. CONCLUSIONS: Multisystem
      neuroprosthetic training effectively counteracts the formation of neurogenic
      bladder dysfunction after severe spinal cord injury and might contribute to
      preserving bladder function and preventing long-term complications in patients
      with severe spinal cord injury.

PMID- 22982432
TI  - In vivo evaluation of the third generation biodegradable stent: a novel approach
      to avoiding the forgotten stent syndrome.
AB  - PURPOSE: Ureteral stents are prone to irritation, encrustation and infection, and
      they require additional procedures for removal. Furthermore, indwelling polymer
      stents are often forgotten with devastating consequences to the patient. We
      describe the degradation time, and physiological and histological responses
      elicited by a novel biodegradable ureteral stent in a porcine model. MATERIALS
      AND METHODS: A total of 16 female Yorkshire pigs were used in the study. Ten
      biodegradable UripreneTM stents and 6 biostable PolarisTM stents were
      cystoscopically inserted unilaterally in 2 groups of animals. Excretory urogram,
      and blood and urine tests were performed on different days until day 28.
      Biostable stents were removed on day 21. On day 28 all pigs underwent necropsy
      for microscopic and histological evaluation. RESULTS: Nine of the 10
      biodegradable stents (90%) degraded completely by 4 weeks, while 1 pig had 3
      fragments smaller than 1.5 cm in the bladder. Excretory urogram showed equivalent
      drainage and significantly less hydronephrosis in biodegradable stented kidneys.
      Blood and urine parameters were similar in the 2 groups. A transient increase in
      serum creatinine on day 7 in 40% of the pigs with a degradable stent resolved by
      day 10. There were significantly fewer abnormal histological findings in the
      degradable stent group. We evaluated drainage characteristics in an unobstructed
      ureter and results may not be representative of what develops in obstructed
      ureters. CONCLUSIONS: The third generation biodegradable stent is a safe,
      effective alternative to conventional polymer stents, resulting in equivalent
      drainage and less hydronephrosis.

PMID- 22982433
TI  - Connaught and Russian strains showed the highest direct antitumor effects of
      different Bacillus Calmette-Guerin substrains.
AB  - PURPOSE: Evolutionarily early and late bacillus Calmette-Guerin substrains are
      genetically distinct, showing different antigenic determinants. While it was
      suggested that this may influence the immunostimulatory effects of bacillus
      Calmette-Guerin as a vaccine in the context of tuberculosis, to our knowledge the
      impact of these genetic differences on the antitumor activity of bacillus
      Calmette-Guerin remains unknown. We compared the direct antitumor capacity and
      the ability to trigger cytokine production of 8 evolutionarily early and late BCG
      substrains in urothelial bladder cancer cell lines. MATERIALS AND METHODS: The
      T24, J82 and RT4 bladder tumor cell lines were cultured with different doses of 3
      evolutionarily early bacillus Calmette-Guerin substrains (Japan, Moreau and
      Russian) and 5 evolutionarily late strains (Connaught, Danish, Glaxo, Phipps and
      Tice). The inhibition of cell proliferation at different time points and the
      production of interleukin-6 and 8 in cell culture supernatants were measured.
      RESULTS: For T24 and J82 cells Russian and Connaught induced the highest
      inhibition of cell proliferation and cytokine production, triggering values up to
      threefold higher than the other bacillus Calmette-Guerin strains. In contrast,
      Glaxo and Phipps (for T24 cells) and Glaxo and Tice (for J82 cells) were the
      least efficacious. For RT4 all bacillus Calmette-Guerin strains inhibited cell
      proliferation to a similar extent and induced low levels of only interleukin-8
      except the Danish and Glaxo strains, which were less efficacious. CONCLUSIONS:
      Russian and Connaught, which are evolutionarily early and late substrains,
      respectively, are the most efficacious bacillus Calmette-Guerin strains for
      inhibiting cell proliferation and inducing cytokine production. Glaxo is the
      least efficacious strain.

PMID- 22982434
TI  - Using multiple analytical methods to improve phylogenetic hypotheses in Minaria
      (Apocynaceae).
AB  - Metastelmatinae is a neotropical subtribe of Asclepiadoideae (Apocynaceae),
      comprising 13 genera and around 260 species whose phylogenetic relationships are
      often unresolved or incongruent between plastid and nuclear datasets. The genus
      Minaria is one of the first lineages to emerge in the Metastelmatinae and is
      highly supported based on plastid markers. It comprises 21 species, most of which
      are endemic to small areas with open vegetation in the Espinhaco Range, Brazil.
      In the work presented here, we use plastid (rps16, trnH-psbA, trnS-trnG, and trnD
      trnT) and nuclear (ITS and ETS) datasets to investigate the relationships within
      Minaria. We show that the three methods mostly used in phylogenetic studies,
      namely, maximum parsimony, maximum likelihood, and Bayesian Inference, have
      different performances and that a pluralistic analytical approach combining
      results from them can increase tree resolution and clade confidence, providing
      valuable phylogenetic information.

PMID- 22982435
TI  - MITOS: improved de novo metazoan mitochondrial genome annotation.
AB  - About 2000 completely sequenced mitochondrial genomes are available from the NCBI
      RefSeq data base together with manually curated annotations of their protein
      coding genes, rRNAs, and tRNAs. This annotation information, which has
      accumulated over two decades, has been obtained with a diverse set of
      computational tools and annotation strategies. Despite all efforts of manual
      curation it is still plagued by misassignments of reading directions, erroneous
      gene names, and missing as well as false positive annotations in particular for
      the RNA genes. Taken together, this causes substantial problems for fully
      automatic pipelines that aim to use these data comprehensively for studies of
      animal phylogenetics and the molecular evolution of mitogenomes. The MITOS
      pipeline is designed to compute a consistent de novo annotation of the
      mitogenomic sequences. We show that the results of MITOS match RefSeq and MitoZoa
      in terms of annotation coverage and quality. At the same time we avoid biases,
      inconsistencies of nomenclature, and typos originating from manual curation
      strategies. The MITOS pipeline is accessible online at http://mitos.bioinf.uni
      leipzig.de.

PMID- 22982436
TI  - The lemur revolution starts now: the genomic coming of age for a non-model
      organism.
AB  - Morris Goodman was a revolutionary. Together with a mere handful of like-minded
      scientists, Morris established himself as a leader in the molecular phylogenetic
      revolution of the 1960s. The effects of this revolution are most evident in this
      journal, which he founded in 1992. Happily for lemur biologists, one of Morris
      Goodman's primary interests was in reconstructing the phylogeny of the primates,
      including the tooth-combed Lorisifomes of Africa and Asia, and the Lemuriformes
      of Madagascar (collectively referred to as the suborder Strepsirrhini). This
      paper traces the development of molecular phylogenetic and evolutionary genetic
      trends and methods over the 50-year expanse of Morris Goodman's career,
      particularly as they apply to our understanding of lemuriform phylogeny,
      biogeography, and biology. Notably, this perspective reveals that the lemuriform
      genome is sufficiently rich in phylogenetic signal such that the very earliest
      molecular phylogenetic studies - many of which were conducted by Goodman himself 
      have been validated by contemporary studies that have exploited advanced
      computational methods applied to phylogenomic scale data; studies that were
      beyond imagining in the earliest days of phylogeny reconstruction. Nonetheless,
      the frontier still beckons. New technologies for gathering and analyzing genomic
      data will allow investigators to build upon what can now be considered a nearly
      known phylogeny of the Lemuriformes in order to ask innovative questions about
      the evolutionary mechanisms that generate and maintain the extraordinary breadth
      and depth of biological diversity within this remarkable clade of primates.

PMID- 22982437
TI  - Phylogeny of halictine bees supports a shared origin of eusociality for Halictus
      and Lasioglossum (Apoidea: Anthophila: Halictidae).
AB  - The halictid bees are excellent models for the study of social evolution because
      greater social diversity and plasticity are observed in the tribe Halictini than
      in any other comparable taxonomic group. We examine the evolutionary
      relationships within the subfamily Halictinae ("sweat bees") to investigate the
      origins of social behaviour within the tribe Halictini. We present a new
      phylogeny of the subfamily Halictinae based on three nuclear genes (elongation
      factor-1 alpha, wingless, and long-wavelength rhodopsin) and one mitochondrial
      gene (cytochrome c oxidase 1) sequenced for 206 halictine bees. We use model
      based character reconstruction to infer the probability of a shared eusocial
      ancestor for the genera Halictus and Lasioglossum, the two genera of Halictini
      which display eusociality. Our results suggest a high probability for a single
      origin of eusociality for these two genera, contradicting earlier views of
      separate origins within each taxon. Fossil-calibrated divergence estimates place
      this ancestor at approximately 35 million years ago, about 14 million years
      earlier than previous estimates of eusocial origins in the halictid bees.

PMID- 22982438
TI  - Regulation of phosphorylation at Ser(1303) of GluN2B receptor in the postsynaptic
      density.
AB  - Neuronal N-methyl-D-aspartate subtype of ionotropic glutamate receptor (NMDAR)
      that plays essential roles in excitatory synaptic transmission is regulated by
      phosphorylation. However, the kinases and phosphatases involved in this
      regulation are not completely known. We show that the GluN2B subunit of NMDAR is
      phosphorylated at Ser(1303) by protein kinase C (PKC) and is dephosphorylated by
      protein phosphatase 1 (PP1), but not protein phosphatase 2A (PP2A) in isolated
      postsynaptic density (PSD). Although PSD is known to harbor PKC, PP1 and PP2A,
      their ability to regulate phosphorylation of GluN2B-Ser(1303) would depend on the
      accessibility of GluN2B-Ser(1303) to these proteins. Since PSD preparation is
      likely to maintain the organization of its component proteins as inside neurons,
      accessibility of kinases and phosphatases to GluN2B-Ser(1303)in vivo would be
      addressed by experiments using this system. Using an antibody specific for the
      phosphorylated state of GluN2B-Ser(1303) we demonstrate that PP1 is the major
      phosphatase in rat brain PSD that can dephosphorylate the GluN2B-Ser(1303)
      endogenous to PSD. We also show that PKC present in PSD can phosphorylate GluN2B
      Ser(1303). The events reported here might be important in regulating GluN2B
      Ser(1303) phosphorylation in vivo.

PMID- 22982439
TI  - Derivation of a chronic oral reference dose for cobalt.
AB  - Cobalt (Co) is an essential element in humans as a component of vitamin B12.
      However, at high levels Co exposure has been shown to have detrimental effects.
      This study was designed to identify a chronic oral reference dose (RfD) for Co.
      Currently available data indicate that non-cancer health effects associated with
      Co exposure may include hematological, neurological, immunological, reproductive,
      cardiovascular, and endocrine responses. This analysis employs the standard US
      EPA risk assessment methodology for establishing a chronic RfD. In this analysis,
      the Jaimet and Thode (1955) 10-week, multiple dose human study of thyroid effects
      (decreased iodine uptake) in children was determined to be the most robust and
      sensitive study for identifying a potential point of departure dose (POD). A dose
      of 0.9 mgCo/kg-day was chosen as the POD. Consistent with the US EPA's previous
      derivation of the perchlorate RfD, which is also based on decreased iodine uptake
      in humans, we considered several uncertainly factors (UFs), and determined that a
      factor of 10 for human variability was appropriate, as well as a factor of three
      for database adequacy. Applying an aggregate uncertainty factor of 30 to the POD
      yields a chronic oral RfD of 0.03 mg/kg-day. We believe this value would be
      protective of non-cancer health effects in the general population for a lifetime
      of daily exposure to Co.

PMID- 22982440
TI  - Immunophenotypic identification and characterization of tumor cells and
      infiltrating cell populations in meningiomas.
AB  - Meningiomas are primary tumors of the central nervous system composed of both
      neoplastic and other infiltrating cells. We determined the cellular composition
      of 51 meningioma samples by multiparameter flow cytometric (MFC)
      immunophenotyping and investigated the potential relationship between mRNA and
      protein expression levels of neoplastic cells. For immunophenotypic, morphologic,
      and cytogenetic characterization of individual cell populations, a large panel of
      markers was used together with phagocytic/endocytic functional assays and MFC
      sorting. Overall, our results revealed coexistence of CD45(-) neoplastic cells
      and CD45(+) immune infiltrating cells in all meningiomas. Infiltrating cells
      included tissue macrophages, with an HLA-DR(+)CD14(+)CD45(+)CD68(+)CD16(-/+)CD33(
      /+) phenotype and high phagocytic/endocytic activity, and a small proportion of
      cytotoxic lymphocytes (mostly T CD8(+) and natural killer cells). Tumor cells
      expressed multiple cell adhesion proteins, tetraspanins, HLA-I/HLA-DR molecules,
      complement regulatory proteins, cell surface ectoenzymes, and growth factor
      receptors. Noteworthy, the relationship between mRNA and protein levels was
      variable, depending on the proteins evaluated and the level of infiltration by
      immune cells. In summary, our results indicate that MFC immunophenotyping
      provides a reliable tool for the characterization of the patterns of protein
      expression of different cell populations coexisting in meningioma samples, with a
      more accurate measure of gene expression profiles of tumor cells at the
      functional/protein level than conventional mRNA microarray, independently of the
      degree of infiltration of the tumor by immune cells.

PMID- 22982441
TI  - Oncostatin M is a growth factor for Ewing sarcoma.
AB  - Primary bone tumors, osteosarcomas and chondrosarcomas, derive from mesenchymal
      stem cells committed into osteoblasts and chondrocytes; in Ewing sarcomas (ESs),
      the oncogenic fusion protein EWS-FLI1 prevents mesenchymal differentiation and
      induces neuroectodermic features. Oncostatin M (OSM) is a cytokine from the IL-6
      family that modulates proliferation and differentiation in numerous cells. The
      basis for inhibition versus induction of proliferation by this cytokine is
      obscure, although MYC was described as a potent molecular switch in OSM
      signaling. We show herein that, in contrast to osteosarcomas and chondrosarcomas,
      for which OSM was cytostatic, OSM induced proliferation of ES cell lines.
      Knockdown experiments demonstrated that growth induction by OSM depends on both
      types I [leukemia inhibitory factor receptor (LIFR)] and II [OSM receptor (OSMR)]
      receptors, high STAT3 activation, and induction of MYC to a high expression
      level. Indeed, ES cell lines, mice xenografts, and patient biopsy specimens
      poorly expressed LIF, precluding LIFR lysosomal degradation and OSMR
      transcriptional induction, thus leading to a high LIFR/OSMR ratio. Because other
      neuroectodermic tumors (ie, glioma, medulloblastoma, and neuroblastoma) had a
      similar expression profile, the main role of EWS-FLI1 could be through
      maintenance of stemness and neuroectodermic features, characterized by a low LIF,
      a high LIFR/OSMR ratio, and high MYC expression. Thus, this study on rare bone
      malignancies gives valuable insights on more common cancer regulatory mechanisms
      and could provide new therapeutic opportunities.

PMID- 22982442
TI  - Inhibition of NF-kappaB activation by 4-hydroxynonenal contributes to liver
      injury in a mouse model of alcoholic liver disease.
AB  - Long-term alcohol exposure sensitizes hepatocytes to tumor necrosis factor-alpha
      (TNF) cytotoxicity. 4-Hydroxynonenal (4-HNE) is one of the most abundant and
      reactive lipid peroxides. Increased hepatic 4-HNE contents present in both human
      alcoholics and alcohol-fed animals. In the present study, we investigated the
      effects of intracellular 4-HNE accumulation on TNF-induced hepatotoxicity and its
      potential implication in the pathogenesis of alcoholic liver disease. Male
      C57BL/6 mice were fed an ethanol-containing or a control diet for 5 weeks. Long
      term alcohol exposure increased hepatic 4-HNE and TNF levels. Cell culture
      studies revealed that 4-HNE, at nontoxic concentrations, sensitized hepatocytes
      to TNF killing, which was associated with suppressed NF-kappaB transactivity.
      Further investigation demonstrated that 4-HNE prevented TNF-induced inhibitor of
      kappaBalpha phosphorylation without affecting upstream IkappaB kinase activity.
      An immunoprecipitation assay revealed that increased 4-HNE content was associated
      with increased formation of 4-HNE-inhibitor of kappaBalpha adduction in both 4
      HNE-treated hepatocytes and in the livers of alcohol-fed mice. Prevention of
      intracellular 4-HNE accumulation by bezafibrate, a peroxisome proliferator
      activated receptor-alpha agonist, protected hepatocytes from TNF killing via NF
      kappaB activation. Supplementation of N-acetylcysteine, a glutathione precursor,
      conferred a protective effect on alcohol-induced liver injury in mice, was
      associated with decreased hepatic 4-HNE formation, and improved hepatic NF-kappaB
      activity. In conclusion, increased 4-HNE accumulation represents a potent and
      clinically relevant sensitizer to TNF-induced hepatotoxicity. These data support
      the notion that removal of intracellular 4-HNE can serve as a potential
      therapeutic option for alcoholic liver disease.

PMID- 22982443
TI  - miR-200c inhibits melanoma progression and drug resistance through down
      regulation of BMI-1.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs that play crucial roles in
      tumorigenesis and tumor progression. Melanoma is the most aggressive skin cancer
      that is resistant or rapidly develops resistance to a variety of chemotherapeutic
      agents. The role of miRNAs in melanoma progression and drug resistance has not
      been well studied. Herein, we demonstrate that miR-200c is down-regulated in
      melanomas (primary and metastatic) compared with melanocytic nevi. Overexpression
      of miR-200c in melanoma cells resulted in significantly decreased cell
      proliferation and migratory capacity as well as drug resistance. miR-200c
      overexpression resulted in significant down-regulation of BMI-1, ABCG2, ABCG5,
      and MDR1 expression and in a concomitant increase in E-cadherin levels. Knockdown
      of BMI-1 showed similar effects as miR-200c overexpression in melanoma cells. In
      addition, miR-200c overexpression significantly inhibited melanoma xenograft
      growth and metastasis in vivo, and this correlated with diminished expression of
      BMI-1 and reduced levels of E-cadherin in these tumors. The effects of miR-200c
      on melanoma cell proliferation and migratory capacity and on self-renewal were
      rescued by overexpression of Bmi-1, and the reversal of these phenotypes
      correlated with a reduction in E-cadherin expression and increased levels of
      ABCG2, ABCG5, and MDR1. Taken together, these findings demonstrate a key role for
      miR-200c in melanoma progression and drug resistance. These results suggest that
      miR-200c may represent a critical target for increasing melanoma sensitivity to
      clinical therapies.

PMID- 22982444
TI  - Insights into phylogeny, sex function and age of Fragaria based on whole
      chloroplast genome sequencing.
AB  - The cultivated strawberry is one of the youngest domesticated plants, developed
      in France in the 1700s from chance hybridization between two western hemisphere
      octoploid species. However, little is known about the evolution of the species
      that gave rise to this important fruit crop. Phylogenetic analysis of chloroplast
      genome sequences of 21 Fragaria species and subspecies resolves the western North
      American diploid F. vesca subsp. bracteata as sister to the clade of
      octoploid/decaploid species. No extant tetraploids or hexaploids are directly
      involved in the maternal ancestry of the octoploids. There is strong geographic
      segregation of chloroplast haplotypes in subsp. bracteata, and the gynodioecious
      Pacific Coast populations are implicated as both the maternal lineage and the
      source of male-sterility in the octoploid strawberries. Analysis of sexual system
      evolution in Fragaria provides evidence that the loss of male and female function
      can follow polyploidization, but does not seem to be associated with loss of self
      incompatibility following genome doubling. Character-state mapping provided
      insight into sexual system evolution and its association with loss of self
      incompatibility and genome doubling/merger. Fragaria attained its circumboreal
      and amphitropical distribution within the past one to four million years and the
      rise of the octoploid clade is dated at 0.372-2.05 million years ago.

PMID- 22982445
TI  - Leukotriene D4 induces cognitive impairment through enhancement of CysLT1 R
      mediated amyloid-beta generation in mice.
AB  - Amyloid plaques in the extracellular parenchyma mainly consist of amyloid-beta
      peptides (Abeta), one of the pathological hallmarks in Alzheimer's disease (AD).
      In the present study, we examined neuroinflammation, amyloidogenesis, and memory
      performance following intracerebral infusions of leukotriene D4 (LTD4) in mice.
      The results demonstrated that intracerebral infusions of LTD4 (1 ng/mouse)
      produced memory impairment as determined by Morris water maze test and Y-maze
      test in mice, and caused the accumulation of Abeta1-40 and Abeta1-42 in the
      hippocampus and cortex through increased activity of beta- and gamma-secretases
      accompanied with increased expression of amyloid precursor protein (APP). LTD4
      also induced expression of cysteinyl leukotriene receptor 1 (CysLT(1)R) and NF
      kappaB p65 in the hippocampus and cortex. Pretreatment with pranlukast (1.5
      ng/mouse, intracerebroventricularly), a CysLT(1)R antagonist, blocked LTD4
      induced amyloidogenesis, memory deficits. Pranlukast (0.6 MUM) also prevented
      LTD4 (20 nM)-induced amyloidogenesis in the cultured neurons in vitro. Moreover,
      LTD4-induced increases in CysLT(1)R and NF-kappaB p65 in the brain were also
      attenuated by pranlukast. These results suggest that LTD4 increases Abeta peptide
      burden via activation of CysLT(1)R, which further affects APP levels and activity
      of beta- and gamma-secretases via the NF-kappaB pathway. Our findings identify
      CysLT(1)R signaling as a novel proinflammatory and proamyloidogenic pathway, and
      suggest a rationale for development of therapeutics targeting the CysLT(1)R in
      neuroinflammatory diseases such as AD.

PMID- 22982446
TI  - Age-related changes in the acoustic startle reflex in Fischer 344 and Long Evans
      rats.
AB  - The behavioral consequences of age-related changes in the auditory system were
      studied in Fischer 344 (F344) rats as a model of fast aging and in Long Evans
      (LE) rats as a model of normal aging. Hearing thresholds, the strength of the
      acoustic startle responses (ASRs) to noise and tonal stimuli, and the efficiency
      of the prepulse inhibition (PPI) of ASR were assessed in young-adult, middle
      aged, and aged rats of both strains. Compared with LE rats, F344 rats showed
      larger age-related hearing threshold shifts, and the amplitudes of their startle
      responses were mostly lower. Both rat strains demonstrated a significant decrease
      of startle reactivity during aging. For tonal stimuli, this decrease occurred at
      an earlier age in the F344 rats: middle-aged F344 animals expressed similar
      startle reactivity as aged F344 animals, whereas middle-aged LE animals had
      similar startle reactivity as young-adult LE animals. For noise stimuli, on the
      other hand, a similar progression of age-related ASR changes was found in both
      strains. No significant relationship between the hearing thresholds and the ASR
      amplitudes was found within any age group. Auditory PPI was less efficient in
      F344 rats than in LE rats. An age-related reduction of the PPI of ASR was
      observed in rats of both strains; however, a significant reduction of PPI
      occurred only in aged rats. The results indicate that the ASR may serve as an
      indicator of central presbycusis.

PMID- 22982447
TI  - On the universal core of bioenergetics.
AB  - Living cells are able to harvest energy by coupling exergonic electron transfer
      between reducing and oxidising substrates to the generation of chemiosmotic
      potential. Whereas a wide variety of redox substrates is exploited by prokaryotes
      resulting in very diverse layouts of electron transfer chains, the ensemble of
      molecular architectures of enzymes and redox cofactors employed to construct
      these systems is stunningly small and uniform. An overview of prominent types of
      electron transfer chains and of their characteristic electrochemical parameters
      is presented. We propose that basic thermodynamic considerations are able to
      rationalise the global molecular make-up and functioning of these chemiosmotic
      systems. Arguments from palaeogeochemistry and molecular phylogeny are employed
      to discuss the evolutionary history leading from putative energy metabolisms in
      early life to the chemiosmotic diversity of extant organisms. Following the
      Occam's razor principle, we only considered for this purpose origin of life
      scenarios which are contiguous with extant life. This article is part of a
      Special Issue entitled: The evolutionary aspects of bioenergetic systems.

PMID- 22982448
TI  - Global and comparative proteomic profiling of overwintering and developing
      mountain pine beetle, Dendroctonus ponderosae (Coleoptera: Curculionidae),
      larvae.
AB  - BACKGROUND: Mountain pine beetles, Dendroctonus ponderosae Hopkins (Coleoptera:
      Curculionidae), are native to western North America, but have recently begun to
      expand their range across the Canadian Rocky Mountains. The requirement for
      larvae to withstand extremely cold winter temperatures and potentially toxic host
      secondary metabolites in the midst of their ongoing development makes this a
      critical period of their lives. RESULTS: We have uncovered global protein
      profiles for overwintering mountain pine beetle larvae. We have also
      quantitatively compared the proteomes for overwintering larvae sampled during
      autumn cooling and spring warming using iTRAQ methods. We identified 1507 unique
      proteins across all samples. In total, 33 proteins exhibited differential
      expression (FDR < 0.05) when compared between larvae before and after a cold snap
      in the autumn; and 473 proteins exhibited differential expression in the spring
      when measured before and after a steady incline in mean daily temperature.
      Eighteen proteins showed significant changes in both autumn and spring samples.
      CONCLUSIONS: These first proteomic data for mountain pine beetle larvae show
      evidence of the involvement of trehalose, 2-deoxyglucose, and antioxidant enzymes
      in overwintering physiology; confirm and expand upon previous work implicating
      glycerol in cold tolerance in this insect; and provide new, detailed information
      on developmental processes in beetles. These results and associated data will be
      an invaluable resource for future targeted research on cold tolerance mechanisms
      in the mountain pine beetle and developmental biology in coleopterans.

PMID- 22982449
TI  - Measurement and conceptual modelling of herbicide transport to field drains in a
      heavy clay soil with implications for catchment-scale water quality management.
AB  - Propyzamide and carbetamide are essential for blackgrass control in oilseed rape
      production. However, both of these compounds can contaminate surface waters and
      pose compliance problems for water utilities. The transport of propyzamide and
      carbetamide to an instrumented field drain in a small clay headwater tributary of
      the Upper Cherwell catchment was monitored over a winter season. Despite having
      very different sorption and dissipation properties, both herbicides were
      transported rapidly to the drain outlet in the first storm event after
      application, although carbetamide was leached more readily than propyzamide. A
      simple conceptual model was constructed to represent solute displacement from
      mobile pore water and preferential flow to drains. The model was able to
      reproduce the timing and magnitude of herbicide losses well, lending support to
      its conceptual basis. Measured losses in drainflow in the month following
      application were 1.1 and 8.1%, respectively, for propyzamide and carbetamide.
      Differences were due to a combination of differences in herbicide mobility and
      due to the fact that the monitoring period for carbetamide was hydrologically
      more active. For both compounds, losses were greater than those typically
      reported elsewhere for other herbicides. The data suggest that drainflow is the
      dominant pathway for the transfer of these herbicides to the catchment outlet,
      where water is abstracted for municipal supply. This imposes considerable
      constraints on the management options available to reduce surface water
      concentrations of herbicides in this catchment.

PMID- 22982450
TI  - Redox-sensitivity and mobility of selected pharmaceutical compounds in a low flow
      column experiment.
AB  - In this study a laboratory column experiment under water saturated conditions was
      conducted to investigate the transport behaviour of the pharmaceutical compounds
      sulfamethoxazole, carbamazepine, diclofenac, and ibuprofen under varying nitrate
      concentrations. Organic rich sediment (f(OC)=0.01) and surface water from a
      formerly investigated field site were used. The water was spiked with the four
      compounds and the specific redox conditions in the column (0.351 m height) were
      varied throughout the experiment by adding nitrate in the influent water.
      Stepwise controlled decreasing influent nitrate concentrations between 131 and 20
      mg L(-1) were applied in the course of the experiment which lasted 71 days. This
      established temporarily denitrifying conditions in the column during the
      reduction of nitrate. Sulfamethoxazole was severely influenced by this process.
      During denitrification sulfamethoxazole concentrations in the effluent water
      decreased rapidly and significantly. This experiment demonstrates the strong
      dependency of sulfamethoxazole transformation specifically on nitrate reducing
      redox conditions and therefore may help to explain the wide ranges of reported
      degradability for this compound. Ibuprofen was more stable under denitrifying
      redox conditions. Both for carbamazepine and diclofenac apparent retardation was
      observed. For carbamazepine this was attributed to sorption and also to
      degradation. For diclofenac nitrate controlled degradation seems the dominating
      process for the apparent retardation of this compound.

PMID- 22982451
TI  - Selenium and its species in the aquatic moss Fontinalis antipyretica.
AB  - The ability of the widely distributed aquatic moss Fontinalis antipyretica to
      take up Se from water was studied. Nine locations in the Notranjska region
      (Slovenia) with different land use in the catchment were sampled for water and
      moss in the year 2010 in spring, summer and autumn. The concentrations of Se in
      water at all locations did not exceed 0.2 ng mL(-1). F. antipyretica took up Se
      in the range between 345 and 2250 ng g(-1). All results for Se are expressed on
      dry matter basis. The Se content varied depending on the location and season. The
      highest concentration (2250 +/- 170 ng g(-1)) of Se was found in the Zerovniscica
      stream that flows through an agricultural area with dairy farming. The fraction
      of insoluble Se compounds in the residue after enzymatic hydrolysis using
      protease (XIV) was around 75%. Soluble Se compounds in the enzymatic extract of
      F. antipyretica were separated and measured using HPLC coupled to ICP-MS. Se(IV)
      and Se(VI) were found but no organic Se compounds were detected, even at the
      highest concentration.

PMID- 22982452
TI  - Potential extinction of Antarctic endemic fungal species as a consequence of
      global warming.
AB  - Cryomyces spp. are fungi adapted to the harsh conditions of the McMurdo Dry
      Valleys in the Antarctic. The structure of their cell wall is one of the main
      factors for their uncommon ability to survive external stressors. The cells are,
      in fact, embedded in a thick and strongly melanised cell wall encrusted with
      black rigid plaques giving a supplementary protection and making them practically
      impregnable and refractory even to commercial enzymes including chitinases and
      glucanases. The Antarctic fungus Lecanicillium muscarium CCFEE 5003, able to
      produce an arsenal of lytic enzymes, including chitinases and glucanases, is
      known for its ability to degrade the cell walls of different food spoiling and
      opportunistic fungi as well as plant pathogenic Oomycota. Active cells of
      Cryomyces spp. were cultivated in dual culture with the mycoparasitic fungus both
      in liquid and solid media. Light microscope observations revealed that the cell
      walls of Cryomyces were heavily decayed. This resulted in the release of
      protoplasts. Hyphae penetration was evident with both scanning and transmission
      electron microscope observations. Due to its ecological amplitude (i.e.
      temperature growth range 0-28  degrees C), the parasitic fungus could easily
      expand its area of distribution as a consequence of global warming by invading
      new areas towards the interior of the continent. The establishment of
      interactions with organisms living at present in border ecosystems may lead to
      extinction of extremely specialized and poorly competitive entities.

PMID- 22982453
TI  - Isolation of a new meroterpene and inhibitors of nitric oxide production from
      Psoralea corylifolia fruits guided by TLC bioautography.
AB  - A new meroterpene, psoracorylifol F (1), was isolated from Psoralea corylifolia
      fruits, along with two known meroterpenes (2 and 3), guided by TLC bioautography
      against O(2)(-) radicals. The structure of 1 was elucidated by means of NMR,
      HRESIMS, and X-ray crystallographic analysis. All the three metroterpenes
      possessed potential inhibitory activity against LPS-induced NO production in RAW
      264.7 cells with IC(50) values ranging from 7.71 to 27.63MUM.

PMID- 22982454
TI  - Preparation and evaluation of self-microemulsifying drug delivery system of
      baicalein.
AB  - The main object of this work is to prepare self-microemulsifying drug delivery
      system (SMEDDS) for oral bioavailability enhancement of a poorly water-soluble
      drug, baicalein. SMEDDS is the mixture of surfactants, cosurfactants, and oils,
      which are emulsified in aqueous media under conditions of gentle agitation or
      gastrointestinal motility. Solubility of baicalein was determined in various
      vehicles. Pseudo-ternary phase diagrams were constructed to identify the
      efficient self-emulsification region and droplet size distributions of the
      resultant microemulsions were determined using a particle size analyzer.
      Optimized SMEDDS formulations for baicalein were Cremophor RH40 (53.57%) as
      surfactant, Transcutol P (21.43%) as cosurfactant, and Caprylic capric
      triglyceride (ODO, 25%) as oil. The drug release rate of SMEDDS was significantly
      higher than that of the baicalein suspension. Comparison of the pharmacokinetics
      between baicalein-loaded SMEDDS and baicalein suspension was also performed in
      rats. The plasma concentrations of baicalein and baicalin, its mainly conjugated
      metabolite, were determined by HPLC method. The in vivo results showed that the
      absorption of baicalein from SMEDDS resulted in about 200.7% increase in relative
      bioavailability compared with that of the baicalein suspension. Our studies
      illustrated the potential use of SMEDDS for the delivery of hydrophobic
      compounds, such as baicalein by the oral route.

PMID- 22982456
TI  - A successful live donor kidney transplantation after large angiomyolipoma
      excision.
AB  - INTRODUCTION: Angiomyolipoma is the most common benign neoplasm of the kidney.
      Successful transplantation of an AML affected kidney has been reported. However
      it is still often seen as a contraindication to transplantation. PRESENTATION OF
      CASE: A 47-year-old female underwent assessment for a direct specified kidney
      donation to her husband who had end stage renal failure, due to adult polycystic
      kidney disease. Routine pre-operative CT angiography demonstrated a large 6cm*4cm
      AML arising from the upper pole of the right kidney. Right-side hand assisted
      retro-peritoneoscopic live donor nephrectomy with bench tumour excision was
      subsequently performed. Recipient implantation was unremarkable with no
      haemorrhage. DISCUSSION: Histology confirmed a 7cm AML. At 36 months follow up,
      the recipient's serum creatinine was 158MUmol/l and eGFR 40ml/min without the
      need for dialysis at any stage. CONCLUSION: AML should not be a contraindication
      for specified live kidney donation, despite a size of 7cm.

PMID- 22982455
TI  - Early embryonic lethality of mice with disrupted transcription cofactor
      PIMT/NCOA6IP/Tgs1 gene.
AB  - PIMT (also known as PIPMT/NCOA6IP/Tgs1), first isolated as a transcription
      coactivator PRIP (NCOA6)-interacting 96-kDa protein with RNA-binding property,
      possesses RNA methyltransferase activity. As a transcription coactivator binding
      protein, PIMT enhances the nuclear receptor transcriptional activity and its
      methyltransferase property is involved in the formation of the 2,2,7
      trimethylguanosine cap of non-coding small RNAs, but the in vivo functions of
      this gene have not been fully explored. To elucidate the biological functions, we
      used gene targeting to generate mice with a disrupted PIMT/Tgs1 gene. Disruption
      of PIMT gene results in early embryonic lethality due to impairment of
      development around the blastocyst and uterine implantation stages. We show that
      PIMT is expressed in all cells of the E3.5day blastocyst in the mouse. PIMT null
      mutation abolished PIMT expression in all cells of the blastocyst and caused a
      reduction in the expression of Oct4 and Nanog transcription factor proteins in
      the E3.5 blastocyst resulting in the near failure to form inner cell mass (ICM).
      With conditional deletion of PIMT gene, mouse embryonic fibroblasts (MEFs)
      exhibit defective wound healing in the scratch assay and a reduction in cell
      proliferation due to decreased G0/G1 transition and G2/M phase cell cycle arrest.
      We conclude that PIMT/NCOA6IP, which is expressed in all cells of the 3.5 day
      stage blastocyst, is indispensable for early embryonic development.

PMID- 22982457
TI  - eNOS gene polymorphisms modify the association of PM(10) with oxidative stress.
AB  - Previous studies have suggested that air pollution increases various health
      outcomes through oxidative stress and oxidative stress-related genes modify the
      relationship between air pollution and health outcomes. Therefore, we evaluated
      the effect of PM(10) on the levels of malondialdehyde (MDA), oxidative stress
      biomarker, and the effect modification by genetic polymorphisms of eNOS,
      oxidative stress-related gene, in the 560 Korean elderly. We obtained urine
      samples repeatedly from participants during five medical examinations between
      2008 and 2010 and all ambient air pollutant concentration data from the Korea
      National Institute of Environmental Research air quality monitoring system. We
      measured urinary levels of MDA to assess oxidative stress and genotyped eNOS
      (rs1799983, rs2853796, and rs7830). Mixed-effect model was used to estimate the
      effect of PM(10) on the level of oxidative stress biomarker and their
      modification by genotypes. PM(10) showed apparent positive effect on MDA level
      after adjusting for age, sex, BMI, cotinine level, temperature, dew point, levels
      of SO(2), O(3), NO(2), and CO, and season (p=0.0133). Moreover, the association
      of PM(10) with MDA was found only in participants with eNOS GG genotype for
      rs1799983 (p=0.0107), TT genotype for rs2853796 (p=0.0289), or GT genotype for
      rs7830 (p=0.0158) and in participants with a set of risky haplotypes (GTT, GTG,
      GGT, and TGT) (p=0.0093). Our results suggest that PM(10) affect oxidative stress
      in the elderly and eNOS genotype affect the oxidative stress level in regard of
      exposure to PM(10).

PMID- 22982458
TI  - Responses of yellow catfish (Pelteobagrus fulvidraco Richardson) exposed to
      dietary cyanobacteria and subsequent recovery.
AB  - A 120-day toxicity experiment was conducted to investigate the effect of dietary
      cyanobacteria on the growth and liver histopathology of yellow catfish, and
      subsequent recovery when the fish were free of cyanobacteria. Three experimental
      diets were formulated: the control (cyanobacteria-free diet), low-cyanobacteria
      diet (LCD, 32.3 MUg microsystins/g) and high-cyanobacteria diet (HCD, 71.96 MUg
      microsystins/g). Each diet was fed to fish for 60 days and then all fish were
      free of cyanobacteria for a further 60 days. The results showed that a
      significant decrease in the specific growth rate (SGR) was observed in both fish
      fed with the LCD and HCD after a 1st 30-day exposure period, however, no
      significant difference in the SGR between the LCD and control groups was observed
      after a 2nd 30-day exposure period. At the end of the 60 days exposure, all
      examined liver tissues in both doses exhibited what appeared as dose-dependent
      histopathological modifications. After a 60-day recovery, there were no
      significant differences in the SGR among groups, while no obvious
      histopathological alteration was observed in livers of fish previously fed with
      the LCD. The results indicate that the LCD-treated fish have a full recovery
      after a 60-day recovery, but the HCD-treated fish did not.

PMID- 22982461
TI  - Genotype-dependent impairment of hemoglobin clearance increases oxidative and
      inflammatory response in human diabetic atherosclerosis.
AB  - OBJECTIVE: Haptoglobin (Hp) protein is responsible for hemoglobin clearance after
      intra-plaque hemorrhage. Hp gene exists as Hp-1 and Hp-2 alleles and the
      phenotypes show important molecular heterogeneity. We tested the hypothesis that
      hemoglobin clearance may be deficient in diabetic atheroma from patients with Hp2
      2, triggering increased oxidative, inflammatory, and angiogenic patterns compared
      with controls. METHODS AND RESULTS: Forty patients with diabetes mellitus were
      genotyped and their peripheral plaques compared after atherectomy. Plaque
      hemorrhage, iron content, hemoglobin-binding protein CD163, and heme-oxygenase-1
      were quantified. Oxidative, inflammatory, and angiogenic patterns were evaluated
      by measuring myeloperoxidase, interleukin-10, macrophages, vascular cell adhesion
      molecule-1, smooth muscle actin, and plaque neovascularization (CD34/CD31).
      Plaques with Hp2-2 (n=7) had increased hemorrhage (P<0.005), iron content
      (P<0.001), and reduced CD163 expression (P<0.002) compared with controls (n=14).
      Hp2-2 plaques had increased heme-oxygenase-1 protein (P<0.02), myeloperoxidase
      gene (P<0.05), and protein (P<0.0001). Anti-inflammatory interleukin-10 gene
      (P<0.04), and protein expressions (P<0.0001) were decreased in Hp2-2. Finally,
      macrophage (P<0.0001), vascular cell adhesion molecule-1 (P=0.001), smooth muscle
      actin (P=0.002) scores, and neovessels density (P<0.0001) were increased in Hp2
      2. CONCLUSIONS: Genotype-dependent impairment of hemoglobin clearance after intra
      plaque hemorrhage is associated with increased oxidative, inflammatory, and
      angiogenic response in human diabetic atherosclerosis.

PMID- 22982459
TI  - Biglycan induces the expression of osteogenic factors in human aortic valve
      interstitial cells via Toll-like receptor-2.
AB  - OBJECTIVE: Although biglycan (BGN) and oxidized low-density lipoprotein (oxLDL)
      accumulation has been observed in calcific, stenotic aortic valves, their role in
      the pathogenesis of calcific aortic valve disease is poorly understood. We
      hypothesized that soluble BGN induces the osteogenic response in human aortic
      valve interstitial cells via Toll-like receptor (TLR) 2 and TLR4 and mediates the
      proosteogenic effect of oxLDL. METHODS AND RESULTS: Aortic valve interstitial
      cells of stenotic valves express higher levels of BGN. Stimulation of cells from
      normal valves with BGN increased the expression of bone morphogenetic protein-2
      (BMP-2) and alkaline phosphatase (ALP) among the chondrogenic/osteogenic markers
      examined and caused accumulation of calcium deposits. TLR2 silencing, but not
      TLR4 silencing, reduced BMP-2 and ALP levels after BGN stimulation although
      coimmunoprecipitation revealed that BGN interacts with both TLR2 and TLR4. BGN
      induced the phosphorylation of extracellular signal-regulated protein kinase-1/2,
      p38 mitogen-activated protein kinase and nuclear factor-kappaB. Inhibition of
      extracellular-regulated kinase-1/2 markedly reduced the upregulation of BMP-2 and
      ALP expression by BGN whereas inhibition of p38 mitogen-activated protein kinase
      or nuclear factor-kappaB had a moderate effect. Stimulation of aortic valve
      interstitial cells with oxLDL upregulated BGN expression and release. Knockdown
      and neutralization of BGN reduced the effect of oxLDL on BMP-2 and ALP
      expression. CONCLUSIONS: Extracellular soluble BGN induces the expression of BMP
      2 and ALP in human aortic valve interstitial cells primarily via TLR2 and
      contributes to the proosteogenic effect of oxLDL. These findings highlight the
      potential role of soluble BGN and oxLDL in the development of calcific aortic
      valve disease.

PMID- 22982460
TI  - Association of oxidative DNA damage and C-reactive protein in women at risk for
      cardiovascular disease.
AB  - OBJECTIVE: The aim of the current study was to examine the relationship between
      clinical markers of inflammation and 8-oxo-7,8-dihydro-2'deoxyguanosine (8
      oxodG), an oxidative stress marker, in middle-aged women drawn from the HANDLS
      study, a longitudinal epidemiological study. METHODS AND RESULTS: We examined
      commonly assayed markers of inflammation, the DNA base adduct 8-oxodG, a marker
      of oxidative stress, and cardiovascular risk factors in a cohort of women matched
      on age and race in 3 groups (n=39 per group) who had low (<3 mg/L) high
      sensitivity C-reactive protein (hsCRP), mid (>3-20 mg/L), and high (>20 mg/L)
      hsCRP. We found a significant relationship between hsCRP level and the oxidative
      stress marker, 8-oxodG. 8-oxodG was positively correlated with systolic blood
      pressure, pulse pressure, and interleukin-23. hsCRP was associated with obesity
      variables, high-density lipoprotein, serum insulin levels, interleukin-12p70 and
      intracellular adhesion molecule-1. Incubation of primary human endothelial cells
      with hsCRP generated reactive oxygen species in vitro. Furthermore, hsCRP
      specifically induced DNA base lesions, but not other forms of DNA damage,
      including single and double strand breaks. CONCLUSIONS: These data suggest that
      in women 8-oxodG is associated with hsCRP and is independently related to select
      cardiovascular risk factors. Our data in women suggest that hsCRP may contribute
      to cardiovascular disease by increasing oxidative stress.

PMID- 22982462
TI  - Regulation of pattern recognition receptors by the apolipoprotein A-I mimetic
      peptide 4F.
AB  - OBJECTIVE: The apolipoprotein A-I (apoA-I) mimetic peptide 4F favors the
      differentiation of human monocytes to an anti-inflammatory phenotype and
      attenuates lipopolysaccharide (LPS)-induced inflammatory responses. We
      investigated the effects of LPS on the Toll-like receptor (TLR) signaling pathway
      in 4F-differentiated monocyte-derived macrophages. METHODS AND RESULTS: Monocyte
      derived macrophages were pretreated with 4F or vehicle for 7 days. 4F
      downregulated cell-surface TLRs (4, 5, and 6) as determined by flow cytometry. 4F
      attenuated the LPS-dependent upregulation of genes encoding TLR1, 2, and 6 and
      genes of the MyD88-dependent (CD14, MyD88, TRAF6, interleukin-1 receptor
      associated kinase 4, and inhibitor of kappa light polypeptide gene enhancer in B
      cells, kinase beta) and MyD88-independent (interferon regulatory factor 3, TANK
      binding kinase 1, and Toll-interleukin 1 receptor domain-containing adaptor
      inducing interferon-beta) pathways as determined by microarray analysis and
      quantitative reverse transcriptase polymerase chain reaction. Functional analyses
      of monocyte-derived macrophages showed that 4F reduced LPS-dependent TLR4
      recycling, phosphorylation of nuclear factor of kappa light polypeptide gene
      enhancer in B-cells inhibitor, alpha, activation and translocation of nuclear
      factor-kappaB and inhibited the secretion of tumor necrosis factor-alpha and
      interleukin-6 induced by LPS or lipoteichoic acid. These changes were associated
      with depletion of cellular cholesterol and caveolin, components of membrane lipid
      rafts. CONCLUSIONS: These data suggest that disruption of rafts by 4F alters the
      assembly of TLR-ligand complexes in cell membranes and inhibits proinflammatory
      gene expression in monocyte-derived macrophages, thus attenuating the
      responsiveness of macrophages to LPS.

PMID- 22982463
TI  - Clinical and genetic association of serum paraoxonase and arylesterase activities
      with cardiovascular risk.
AB  - OBJECTIVE: Diminished serum paraoxonase and arylesterase activities (measures of
      paraoxonase-1 [PON-1] function) in humans have been linked to heightened systemic
      oxidative stress and atherosclerosis risk. The clinical prognostic use of
      measuring distinct PON-1 activities has not been established, and the genetic
      determinants of PON-1 activities are not known. METHODS AND RESULTS: We
      established analytically robust high-throughput assays for serum paraoxonase and
      arylesterase activities and measured these in 3668 stable subjects undergoing
      elective coronary angiography without acute coronary syndrome and were
      prospectively followed for major adverse cardiovascular events (MACE= death,
      myocardial infarction, stroke) over 3 years. Low serum arylesterase and
      paraoxonase activities were both associated with increased risk for MACE, with
      arylesterase activity showing greatest prognostic value (quartile 4 versus
      quartile 1; hazard ratio 2.63; 95% CI, 1.97-3.50; P<0.01). Arylesterase remained
      significant after adjusting for traditional risk factors, C-reactive protein, and
      creatinine clearance (hazard ratio, 2.20; 95% CI, 1.60-3.02; P<0.01), predicted
      future development of MACE in both primary and secondary prevention populations,
      and reclassified risk categories incrementally to traditional clinical variables.
      A genome-wide association study identified distinct single nucleotide
      polymorphisms within the PON-1 gene that were highly significantly associated
      with serum paraoxonase (1.18*10(-303)) or arylesterase (4.99*10(-116)) activity
      but these variants were not associated with either 3-year MACE risk in an
      angiographic cohort (n=2136) or history of either coronary artery disease or
      myocardial infarction in the Coronary Artery Disease Genome-Wide Replication and
      Meta-Analysis consortium (n~80 000 subjects). CONCLUSIONS: Diminished serum
      arylesterase activity, but not the genetic determinants of PON-1 functional
      measures, provides incremental prognostic value and clinical reclassification of
      stable subjects at risk of developing MACE.

PMID- 22982465
TI  - A set of discrete formulae for the performance of a tsetse population during
      aerial spraying.
AB  - A set of discrete formulae that calculates the hypothetical impact of aerial
      spraying on a tsetse population is derived and the work is thought to be novel.
      Both the original population and the subsequent generations which survive the
      aerial spraying, may ultimately be thought of as deriving from two, distinct
      sources. These origins are, however, neither distinct, nor relevant by the third
      generation. It is for this reason that the female population is considered to be
      composed of the following four categories for the purposes of derivation:
      Original flies which existed as such at the commencement of spraying; original
      pupae which existed as such at the commencement of spraying; the immediate
      descendants of both the aforementioned categories, during spraying; third and
      higher generation descendants. In theory, the latter category is a recurrence
      relation. In practice, the third generation's pupal stage has hardly come into
      existence, even by the end of a completed operation. Implicit in the formulae is
      the assumption of one, temperature-dependent mortality rate for the entire pupal
      stage, a second for the period between eclosion and ovulation and yet a third for
      the entire, adult life-span. Gravid female resistance to the insecticide is
      assumed to be inconsequential. A further assumption of the formulae is that at
      least one male is always available (degree of sterility variable).

PMID- 22982464
TI  - Fibroblast growth factor-2 is required for vasa vasorum plexus stability in
      hypercholesterolemic mice.
AB  - OBJECTIVE: Vasa vasorum are angiogenic in advanced stages of human
      atherosclerosis and hypercholesterolemic mouse models. Fibroblast growth factor-2
      (FGF-2) is the predominant angiogenic growth factor in the adventitia and plaque
      of hypercholesterolemic low-density lipoprotein receptor-deficient/apolipoprotein
      B(100/100) mice (DKO). FGF-2 seems to play a role in the formation of a distinct
      vasa vasorum network. This study examined the vasa vasorum structure and its
      relationship to FGF-2. METHODS AND RESULTS: DKO mice treated with saline,
      antiangiogenic recombinant plasminogen activator inhibitor-1(23) (rPAI-1(23)), or
      soluble FGF receptor 1 were perfused with fluorescein-labeled Lycopersicon
      esculentum lectin. Confocal images of FGF-2-probed descending aorta adventitia
      show that angiogenic vasa vasorum form a plexus-like network in saline-treated
      DKO similar to the FGF-2 pattern of distribution. Mice treated with rPAI-1(23)
      and soluble FGF receptor 1 lack a plexus; FGF-2 and vasa vasorum density and area
      are significantly reduced. A perlecan/FGF-2 complex is critical for plexus
      stability. Excess plasmin produced in rPAI-1(23)-treated DKO mice degrades
      perlecan and destabilizes the plexus. Plasmin activity and plaque size measured
      in DKO and DKO/plasminogen activator inhibitor-1(-)(/-) mice demonstrate that
      elevated plasmin activity contributes to reduced plaque size. CONCLUSIONS: An FGF
      2/perlecan complex is required for vasa vasorum plexus stability. Elevated
      plasmin activity plays a significant inhibitory role in vasa vasorum plexus and
      plaque development.

PMID- 22982466
TI  - Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma
      cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: a
      substudy from the BENEFIT trial.
AB  - Quantitative real-time PCR (qPCR) is an accurate method to quantify Trypanosoma
      cruzi DNA and can be used to follow-up parasitemia in Chagas disease (CD)
      patients undergoing chemotherapy. The Benznidazole Evaluation for Interrupting
      Trypanosomiasis (BENEFIT) study is an international, multicenter, randomized,
      double-blinded and placebo-controlled clinical trial to evaluate the efficacy of
      benznidazole (BZ) treatment in patients with chronic Chagas cardiomyopathy (CCC).
      One important question to be addressed concerns the effectiveness of BZ in
      reducing overall parasite load in CCC patients, even in the absence of
      parasitological cure. This report describes the evaluation of multiple procedures
      for DNA extraction and qPCR-based protocols aiming to establish a standardized
      methodology for the absolute quantification of T. cruzi DNA in Guanidine-EDTA
      blood (GEB) samples. A panel of five primer sets directed to the T. cruzi nuclear
      satellite DNA repeats (Sat-DNA) and to the minicircle DNA conserved regions
      (kDNA) was compared in either SYBR Green or TaqMan systems. Standard curve
      parameters such as, amplification efficiency, coefficient of determination and
      intercept were evaluated, as well as different procedures to generate standard
      samples containing pre-established T. cruzi DNA concentration. Initially, each
      primer set was assayed in a SYBR Green qPCR to estimate parasite load in GEB
      samples from chronic Chagas disease patients. The results achieved from Bayesian
      transmutability analysis elected the primer sets Cruzi1/Cruzi2 (p=0.0031) and
      Diaz7/Diaz8 (p=0.0023) coupled to the QIAamp DNA Kit extraction protocol (silica
      gel column), as the most suitable for monitoring parasitemia in these patients.
      Comparison between the parasite burden of 150 GEB samples of BENEFIT patients
      from Argentina, Brazil and Colombia, prior to drug/placebo administration, was
      performed using Cruzi1/Cruzi2 primers in a SYBR Green approach. The median
      parasitemia found in patients from Argentina and Colombia (1.93 and 2.31 parasite
      equivalents/mL, respectively) was around 20 times higher than the one estimated
      for the Brazilian patients (0.1 parasite equivalents/mL). This difference could
      be in part due to the complexity of T. cruzi genetic diversity, which is a factor
      possibly implicated in different clinical presentations of the disease and/or
      influencing parasitemia levels in infected individuals from different regions of
      Latin America. The results of SYBR Green qPCR assays herein presented prove this
      methodology to be more cost efficient than the alternative use of internal
      fluorogenic probes. In addition, its sensitivity and reproducibility are shown to
      be adequate to detect low parasitemia burden in patients with chronic Chagas
      disease.

PMID- 22982467
TI  - Learner-generated drawing for phonological and orthographic dyslexic readers.
AB  - This study presents an examination of learner-generated drawing for different
      reading comprehension subtypes of dyslexic students and control students. The
      participants were 22 phonological dyslexic students, 20 orthographic dyslexic
      students, 21 double-deficit dyslexic students, and 45 age-, gender-, and IQ
      matched control students. The major evaluation tools included word recognition
      task, orthographic task, phonological awareness task, and scenery texts and
      questions. Comparisons of the four groups of students showed differences among
      phonological dyslexia, orthographic dyslexia, double-deficit dyslexia, and the
      chronological age control groups in pre- and posttest performance of scenery
      texts. Differences also existed in relevant questions and the effect of the
      learner-generated drawing method. The pretest performance showed problems in the
      dyslexic samples in reading the scenery texts and answering relevant questions.
      The posttest performance revealed certain differences among phonological
      dyslexia, orthographic dyslexia, double-deficit dyslexia, and the chronological
      age control group. Finally, all dyslexic groups obtained a great effect from
      using the learner-generated drawing, particularly orthographic dyslexia. These
      results suggest that the learner-generated drawing was also useful for dyslexic
      students, with the potential for use in the classroom for teaching text reading
      to dyslexic students.

PMID- 22982468
TI  - Technology-based orientation programs to support indoor travel by persons with
      moderate Alzheimer's disease: impact assessment and social validation.
AB  - The present study (a) extended the assessment of an orientation program involving
      auditory cues (i.e., verbal messages automatically presented from the
      destinations) with five patients with Alzheimer's disease, (b) compared the
      effects of this program with those of a program with light cues (i.e., a program
      in which strobe lights were used instead of the verbal messages) with the same
      five patients, and (c) conducted a social validation assessment of the two
      programs with 70 university psychology students employed as social raters.
      Results confirmed the effectiveness of the program with auditory cues and showed
      an equally strong impact of the program with light cues with all five patients.
      The psychology students involved in the social validation assessment provided
      significantly higher scores for the program involving light cues on a six-item
      questionnaire. Those scores suggested that this program was perceived as a
      practically and socially preferable choice. The implications of the findings for
      daily contexts dealing with patients with Alzheimer's disease are discussed.

PMID- 22982469
TI  - Changes in NADPH oxidase mRNA level can be detected in blood at inhaled
      corticosteroid treated asthmatic children.
AB  - AIM: Oxidative stress, observed in the asthmatic airways, is not localized only
      to the bronchial system. It would be a great advantage to monitor the oxidative
      stress markers from blood especially in childhood asthma following the
      inflammation. Our aim was to measure the levels of antioxidants and the
      oxidatively damaged biomolecules. We were also interested in the gene expression
      alterations of the free radical source gp91(phox) subunit (CYBB) of the NADPH
      oxidase system, and the antioxidant heme oxygenase-1 (HMOX-1) isoenzyme in the
      blood. Our findings were also examined in the context of medical treatment. MAIN
      METHODS: Oxidative stress parameters via photometric methods, CYBB and HMOX-1
      expressions via real-time PCR were measured in 58 asthmatic and 30 healthy
      children. KEY FINDINGS: Higher blood thiobarbituric acid reactive substances
      (TBARS) (p<0.03) and carbonylated protein (p<0.05) levels were found in the
      asthmatic children than in the controls. The relative expression of CYBB was
      significantly lower (p<0.05) in patients treated with a low daily dose of inhaled
      corticosteroid (ICS), than in asthmatics not receiving ICS therapy. Higher ICS
      doses alone or combined with long acting beta2-receptor agonists did not
      influence the expression significantly. No similar tendency was found as regards
      to HMOX-1 expression. SIGNIFICANCE: Elevated levels of damaged lipid (TBARS) and
      protein (carbonylated) products corroborate the presence of oxidative stress in
      the blood during bronchial asthma and suggest the presence of chronic oxidative
      overload. Our findings also suggest that ICS treatment can influence the relative
      CYBB mRNA expression in circulating leukocytes in a dose dependent manner.

PMID- 22982470
TI  - Insulin receptor and IRS-1 co-immunoprecipitation with SOCS-3, and IKKalpha/beta
      phosphorylation are increased in obese Zucker rat skeletal muscle.
AB  - AIMS: We evaluated if selected pro-inflammatory cytokines and/or the protein
      suppressor of cytokine signaling 3 (SOCS-3) could account for decreased insulin
      stimulated phosphatidylinositol 3-kinase (PI3-K) activity in the skeletal muscle
      of the obese Zucker rat. MAIN METHODS: Eight lean and eight obese Zucker rats
      ~4weeks of age were obtained and allowed to feed ad libitum for 4weeks before
      undergoing hind limb perfusion in the presence of 500MUU/ml insulin. KEY
      FINDINGS: Insulin-stimulated skeletal muscle PI3-K activity and 3-O-methylglucose
      transport rates were reduced (P<0.05) in obese compared to lean animals. IRS-1
      concentration remained unchanged although IRS-1 tyrosine phosphorylation was
      decreased (P<0.05), and IRS-1 serine phosphorylation (pS) was increased (P<0.05)
      in obese animals compared to lean animals. IKKalpha/beta pS and JNK
      theronine/tyrosine phosphorylation was increased (P<0.05) in the obese animals.
      IkappaBalpha concentration was decreased (P<0.05) and IkappaBalpha pS was
      increased (P<0.05) in the obese compared to lean Zucker animals. SOCS-3
      concentration and SOCS-3 co-immunoprecipitation with both insulin receptor beta
      subunit (IR-beta) and IRS-1 were elevated (P<0.05) in obese compared to lean
      animals. IRS-1 co-immunoprecipitation with IR-beta was reduced 56% in the obese
      animals. SIGNIFICANCE: Increased IKKalpha/beta and JNK serine phosphorylation may
      contribute to increasing IRS-1 serine phosphorylation, while concurrent co
      localization of SOCS-3 with both IR-beta and IRS-1 may prevent IRS-1 from
      interacting with IR-beta. These two mechanisms thusly may independently
      contribute to impairing insulin-stimulated PI3-K activation in the skeletal
      muscle of the obese Zucker rat.

PMID- 22982471
TI  - Production, composition and toxicology studies of Enzogenol(r) Pinus radiata bark
      extract.
AB  - Enzogenol(r) pine bark extract is a dietary supplement and food ingredient
      produced by water extraction of Pinus radiata. We present production method,
      composition, and safety data from rat and dog toxicological and human clinical
      studies. The dry powder contains proanthocyanidins (>80%), taxifolin (1-2%),
      other flavonoids and phenolic acids (up to 8%), and carbohydrates (5-10%).
      Reverse mutation assays showed lack of mutagenic activity. Single and 14-day
      repeat dosing in rats and dogs had no influence on body weight, feed consumption,
      blood chemistry, and haematology at any dose level. There were no treatment
      related findings on gross and detailed necroscopy, organ weights, organ weight
      ratios and histology. The only adverse events were emesis and diarrhoea in dogs
      occurring mainly in un-fed condition and at the highest dose level in a total of
      18% of applications. The MTD and NOAEL in the present rat and dog studies were
      2500 and 750 mg/kg/day, respectively. Consumption of 480 mg/day for 6 months and
      960 mg/day for 5 weeks in two human studies showed Enzogenol(r) had no adverse
      influence on liver and kidney function, haematology, and did not cause any
      adverse events. Our studies indicate lack of toxicity of Enzogenol(r) and support
      safe use as a food ingredient.

PMID- 22982472
TI  - Levels of polychlorinated biphenyls and organochlorine pesticides in edible
      shellfish from Xiamen (China) and estimation of human dietary intake.
AB  - Xiamen is a representative coastal city in China. Shellfish is widely consumed by
      local people. A broad spectrum of polychlorinated biphenyls (PCBs) and
      organochlorine pesticides (OCPs) were measured in representative shellfish from
      Xiamen. Despite being banned many years ago, these chemicals were still detected
      at varying levels. The total PCB levels ranged from 0.48 to 3.28 ng/g wet wt. for
      the shellfish surveyed. The tetra-, penta- and hexa-PCB congeners were found to
      be predominant. The estimated WHO-TEQ PCB intakes through shellfish consumption
      ranged from 0.063 to 0.102 pg/kg body wt. for Xiamen adults and children, which
      were significantly lower than tolerable weekly intake. Among OCPs, DDTs were
      predominant, followed by aldrin-like chemicals and endosulfans. The increase in
      aldrin-like chemicals and endosulfans, and the decrease in DDTs were observed in
      this study when compared to historical data in Xiamen. HCHs, chlordanes, HCB,
      heptachlors and mirex were detected with low concentrations in the shellfish. The
      estimated intakes of OCPs were several orders lower than tolerable daily intakes.
      However, the high carcinogenic risk of aldrin and dieldrin were found in the
      measured shellfish species. p,p'-DDD, p'p-DDT, alpha-HCH and beta-HCH in certain
      species should also be concerned for their potential carcinogenic risks.

PMID- 22982473
TI  - The protective effect of Canova homeopathic medicine in cyclophosphamide-treated
      non-human primates.
AB  - BACKGROUND: Canova activates macrophages and indirectly induces lymphocyte
      proliferation. Here we evaluated the effects of Canova in cyclophosphamide
      treated non-human primates. METHODS: Twelve Cebus apella were evaluated. Four
      animals were treated with Canova only. Eight animals were treated with two doses
      of cyclophosphamide (50 mg/kg) and four of these animals received Canova. Body
      weight, biochemistry and hematologic analyses were performed for 40 days.
      Micronucleus and comet assays were performed for the evaluation of DNA damage.
      RESULTS: We observed that cyclophosphamide induced abnormal WBC count in all
      animals. However, the group treated with cyclophosphamide plus Canova presented a
      higher leukocyte count than that which received only cyclophosphamide.
      Cyclophosphamide induced micronucleus and DNA damage in all animals. The
      frequency of these alterations was significantly lower in the Canova group than
      in the group without this medicine. CONCLUSIONS: Our results demonstrated that
      Canova treatment minimizes cyclophosphamide myelotoxicity in C. apella.

PMID- 22982474
TI  - The manipulation of neural and cellular activities by ectopic expression of
      melanopsin.
AB  - Melanopsin (OPN4) is a photosensitive pigment originally found in a subtype of
      retinal ganglion cells and is a 7-transmembrane G-protein-coupled receptor
      (GPCR). Several previous reports showed that ectopic expression of OPN4 can be
      used as an optogenetic tool to control neural and cellular activities in various
      tissues. Compared with other optogenetic pigments, OPN4 is more sensitive to
      light, shows long-lasting activation, and can also control intracellular Ca(2+)
      dynamics. Here, we review how the ectopic expression of OPN4 enables the control
      of neural and cellular activities in vivo. In the retina, the ectopic expression
      of melanopsin in retinal ganglion cells successfully restored the vision of blind
      mice. It has also been reported that ectopic expression of melanopsin in
      orexin/hypocretin neurons enabled control of wakefulness in mice by blue light.
      In addition to neural activity, the ectopic expression of OPN4 has been reported
      to enable circuit control of the nuclear factor of activated T cells (NFAT) to
      enhance blood-glucose homeostasis in mice. We discuss the possibility of
      optogenetic control of other systems through the ectopic expression of OPN4.

PMID- 22982475
TI  - Arsenics as bioenergetic substrates.
AB  - Although at low concentrations, arsenic commonly occurs naturally as a local
      geological constituent. Whereas both arsenate and arsenite are strongly toxic to
      life, a number of prokaryotes use these compounds as electron acceptors or
      donors, respectively, for bioenergetic purposes via respiratory arsenate
      reductase, arsenite oxidase and alternative arsenite oxidase. The recent burst in
      discovered arsenite oxidizing and arsenate respiring microbes suggests the
      arsenic bioenergetic metabolisms to be anything but exotic. The first goal of the
      present review is to bring to light the widespread distribution and diversity of
      these metabolizing pathways. The second goal is to present an evolutionary
      analysis of these diverse energetic pathways. Taking into account not only the
      available data on the arsenic metabolizing enzymes and their phylogenetical
      relatives but also the palaeogeochemical records, we propose a crucial role of
      arsenite oxidation via arsenite oxidase in primordial life. This article is part
      of a Special Issue entitled: The evolutionary aspects of bioenergetic systems.

PMID- 22982476
TI  - Understanding the FMN cofactor chemistry within the Anabaena Flavodoxin
      environment.
AB  - The chemical versatility of flavin cofactors within the flavoprotein environment
      allows them to play main roles in the bioenergetics of all type of organisms,
      particularly in energy transformation processes such as photosynthesis or
      oxidative phosphorylation. Despite the large diversity of properties shown by
      flavoproteins and of the biological processes in which they are involved, only
      two flavin cofactors, FMN and FAD (both derived from the 7,8-dimethyl-10-(1'-D
      ribityl)-isoalloxazine), are usually found in these proteins. Using theoretical
      and experimental approaches we have carried out an evaluation of the effects
      introduced upon substituting the 7- and/or 8-methyls of the isoalloxazine ring in
      the chemical and oxido-reduction properties of the different atoms of the ring on
      free flavins and on the photosynthetic Anabaena Flavodoxin (a flavoprotein that
      replaces Ferredoxin as electron carrier from Photosystem I to Ferredoxin-NADP(+)
      reductase). In Anabaena Flavodoxin both the protein environment and the redox
      state contribute to modulate the chemical reactivity of the isoalloxazine ring.
      Anabaena apoflavodoxin is shown to be designed to stabilise/destabilise each one
      of the FMN redox states (but not of the analogues produced upon substitution of
      the 7- and/or 8-methyls groups) in the adequate proportions to provide Flavodoxin
      with the particular properties required for the functions in which it is involved
      in vivo. The 7- and/or 8-methyl groups of the ixoalloxazine can be discarded as
      the gate for electrons exchange in Anabaena Fld, but a key role in this process
      is envisaged for the C6 atom of the flavin and the backbone atoms of Asn58.

PMID- 22982477
TI  - Kinetic properties and physiological role of the plastoquinone terminal oxidase
      (PTOX) in a vascular plant.
AB  - The physiological role of the plastid terminal oxidase (PTOX) involved in
      plastoquinol oxidation in chloroplasts has been investigated in vivo in tomato
      leaves. Enzyme activity was assessed by non-invasive methods based on the
      analysis of the kinetics of chlorophyll fluorescence changes. In the dark, the
      maximum PTOX rate was smaller than 1 electron per second per PSII. This value was
      further decreased upon light acclimation, and became almost negligible upon
      inhibition of the photosynthetic performances by reducing the CO(2) availability.
      In contrast, prolonged exposure to high light resulted in an increase of the
      overall PTOX activity, which was paralleled by an increased protein accumulation.
      Under all the conditions tested the enzyme activity always remained about two
      orders of magnitude lower than that of electron flux through the linear
      photosynthetic electron pathway. Therefore, PTOX cannot have a role of a safety
      valve for photogenerated electrons, while it could be involved in acclimation to
      high light. Moreover, by playing a major role in the control of the stromal redox
      poise, PTOX is also capable of modulating the balance between linear and cyclic
      electron flow around PSI during the deactivation phase of carbon assimilation
      that follows a light to dark transition.

PMID- 22982478
TI  - G to T transversion at the first nucleotide of exon 26 of the MYH9 gene results
      in a novel missense mutation and abnormal splicing in platelets: comment on "A G
      to C transversion at the last nucleotide of exon 25 of the MYH9 gene results in a
      missense mutation rather than in a splicing defecton" by Vettore et al.

PMID- 22982479
TI  - Antidepressant-like properties of three new alpha2-adrenoceptor antagonists.
AB  - Evidence suggests that depression is associated with an increase in the high
      affinity conformation of the alpha2-adrenoceptors in human brain. Such enhanced
      alpha2-adrenoceptor activity could explain the deficit in central noradrenergic
      transmission described in the aetiology of depression. Thus, administration of
      alpha2-adrenoceptor antagonists augments noradrenaline levels and provides an
      effective therapeutic approach for the treatment of depressive disorders. In
      previous studies, we have characterized three new synthesized guanidine and 2
      aminoimidazoline aromatic derivatives (8b, 17b and 20b) as alpha2-adrenoceptor
      antagonists that are able to increase extracellular concentration of
      noradrenaline in rat brain. The purpose of the present study was to evaluate the
      in vivo antidepressant-like properties of these three new alpha2-adrenoceptor
      antagonists. For that aim, compounds were tested on the tail suspension test
      (TST) and forced swim test (FST), two classically widely-used behavioural
      paradigms for the evaluation of antidepressant-like activity. Compound 8b
      significantly reduced the immobility time at 10, 20 and 40 mg/kg doses in both
      TST and FST. Compound 17b reduced the immobility time at 40 mg/kg in both TST and
      FST. Compound 20b showed a significant decrease in the immobility time at 20
      mg/kg in the TST. As drugs of reference, fluoxetine induced a significant
      antidepressant-like effect in both TST and FST, while mirtazapine induced a
      significant antidepressant-like effect only in the FST. Additionally, none of the
      tested compounds increased locomotor activity or displayed anxiolytic-like
      properties. These results suggest that these new synthesized alpha2-adrenoceptor
      antagonists may be useful as potential antidepressant drugs.

PMID- 22982480
TI  - Monensin potentiates lead chelation efficacy of MiADMSA in rat brain post chronic
      lead exposure.
AB  - The present study evaluates combination therapy with a chelating agent, MiADMSA
      and a Na(+) ionophore, monensin against sub-chronic lead toxicity in rats.
      Animals were exposed to 0.1% lead in drinking water for 16 weeks and then treated
      with either MiADMSA at 50mg/kg body weight, or monensin at 10mg/kg, or both in
      combination for a period of 5 days was administered. Biomarkers indicative of
      oxidative stress like ROS, GSH, GSSG and TBARS demonstrated lead-induced toxic
      manifestations in blood, kidney and brain. Antioxidants like SOD, catalase and
      glutathione peroxidase along with specific lead biomarker, blood ALAD were also
      severely depleted in lead intoxicated animals. Serum parameters and
      histopathological findings supported the said results. MiADMSA treatment during
      both mono- and combination therapy with monensin, restored the antioxidant status
      and recovered biochemical and haematological variables due to lead. However,
      monensin alone was not found to be effective in the given scenario.
      Interestingly, combination therapy in its ability to revert lead-induced overall
      systemic toxicity was only found at par with the MiADMSA monotherapy except for
      its chelation potential. Monensin given in combination with MiADMSA potentiated
      its lead chelation ability especially from brain, along with maintaining the
      normal copper concentrations in the organ unlike MiADMSA monotherapy.

PMID- 22982481
TI  - The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs
      recognition memory formation through interaction with glutamatergic but not
      cholinergic receptor antagonists.
AB  - We previously reported that the selective nociceptin orphanin peptide (NOP)
      receptor agonist, Ro64-6198, impairs mnemonic function through glutamatergic
      dependent mechanisms. The aim of the current study was to determine whether the
      amnesic effects of Ro64-6198 involve a cholinergic component. The effects of
      systemic administration of Ro64-6198 (0.3 and 1 mg/kg, i.p.), the cholinergic
      nicotinic receptor antagonist, mecamylamine (0.1 and 1 mg/kg, s.c.), the
      cholinergic muscarinic receptor antagonist, scopolamine (0.1 and 0.3 mg/kg,
      s.c.), and the glutamatergic NMDA receptor antagonist, MK-801 (0.03 and 0.1
      mg/kg, s.c.), were studied in the mouse object recognition task. All compounds
      tested were effective in disrupting formation of long-term (24-h delay)
      recognition memory. Drug interaction studies were then conducted to reveal the
      existence of functional interactions between NOP receptors and cholinergic and/or
      NMDA receptors. Co-administration of silent doses of Ro64-6198 (0.3 mg/kg) and MK
      801 (0.01 mg/kg) produced clear-cut memory impairment. Similar synergistic
      effects were observed with the combination of mecamylamine (0.03 mg/kg) and
      scopolamine (0.1 mg/kg). In contrast, co-administration of Ro64-6198 (0.3 mg/kg)
      with either mecamylamine (0.03 and 0.1 mg/kg) or scopolamine (0.1 mg/kg) was
      without any effect on recognition memory. These findings suggest that NOP
      receptor may modulate memory formation through a functional interaction with
      glutamatergic but not cholinergic receptors.

PMID- 22982482
TI  - Autophagy, signaling and obesity.
AB  - Autophagy is a cellular pathway crucial for development, differentiation,
      survival and homeostasis. Autophagy can provide protection against aging and a
      number of pathologies such as cancer, neurodegeneration, cardiac disease and
      infection. Recent studies have reported new functions of autophagy in the
      regulation of cellular processes such as lipid metabolism and insulin
      sensitivity. Important links between the regulation of autophagy and obesity
      including food intake, adipose tissue development, beta cell function, insulin
      sensitivity and hepatic steatosis exist. This review will provide insight into
      the current understanding of autophagy, its regulation, and its role in the
      complications associated with obesity.

PMID- 22982483
TI  - Does delay impair localisation in blindsight?
AB  - The unconscious sensorimotor skills which survive compromise of the
      geniculostriate visual pathway have been linked with activity of the dorsal
      stream of extrastriate occipitoparietal cortex. These sensorimotor circuits are
      thought to operate in real time. Therefore, an introduction of a delay between
      visual stimulus presentation and the patient's subsequent motor response should
      severely compromise sensorimotor tasks such as localisation (moving hand or eye
      to the location of a previously presented visual target). We tested this
      hypothesis in patient DB, a well-studied case of blindsight whose localisation
      abilities were first documented in the 1970s. Using eye tracking and hand
      movement recording technologies, as well as stimuli that control for light
      scatter, we verified the original observations of DB's manual and saccadic
      localisation. Remarkably, the introduction of a 4s delay did not compromise his
      ability to localise with either eye or hand. A control experiment reveals that
      this skill does not depend on an opportunity to make a decision at the time of
      stimulus presentation, circumventing the delay using memory. These data suggest
      that DB's manual and saccadic localisation skills do not depend on the circuits
      of the dorsal stream, or that delay, contrary to theory, does not severely
      compromise dorsal sensorimotor skills.

PMID- 22982485
TI  - Foveational complexity in single word identification: contralateral visual
      pathways are advantaged over ipsilateral pathways.
AB  - Recognition of a single word is an elemental task in innumerable cognitive
      psychology experiments, but involves unexpected complexity. We test a
      controversial claim that the human fovea is vertically divided, with each half
      projecting to either the contralateral or ipsilateral hemisphere, thereby
      influencing foveal word recognition. We report a novel haploscope task: the two
      halves of a four-letter word were briefly presented to the two eyes in a Both
      condition (st|ep)(st|ep), a Contralateral condition (st|__)(__|ep), or an
      Ipsilateral condition (__|ep)(st|__), all yielding the same single word percept
      (step). The Both condition yielded superior perceptual recognition, followed by
      the contralateral projection, then the ipsilateral projection. These results
      demonstrate that the structure of the fovea influences even the recognition of
      short, foveally presented words. Projecting different parts of the same word to
      different hemispheres involves unforeseen complexities and opportunities for
      optimizing hemispheric coordination.

PMID- 22982484
TI  - Explaining the encoding/retrieval flip: memory-related deactivations and
      activations in the posteromedial cortex.
AB  - The posteromedial cortex (PMC) is strongly linked to episodic memory and age
      related memory deficits. The PMC shows deactivations during a variety of
      demanding cognitive tasks as compared to passive baseline conditions and has been
      associated with the default-mode of the brain. Interestingly, the PMC exhibits
      opposite levels of functional MRI activity during encoding (learning) and
      retrieval (remembering), a pattern dubbed the encoding/retrieval flip (E/R-flip).
      Yet, the exact role of the PMC in memory function has remained unclear. This
      review discusses the possible neurofunctional and clinical significance of the
      E/R-flip pattern. Regarding neurofunctional relevance, we will review four
      hypotheses on PMC function: (1) the internal orienting account, (2) the self
      referential processing account, (3) the reallocation account, and (4) the bottom
      up attention account. None of these accounts seem to provide a complete
      explanation for the E/R-flip pattern in PMC. Regarding clinical relevance, we
      review work on aging and Alzheimer's disease, indicating that amyloid deposits
      within PMC, years before clinical memory deficits become apparent. High amyloid
      burden within PMC is associated with detrimental influences on memory encoding,
      in particular, the attenuation of beneficial PMC deactivations. Finally, we
      discuss functional subdivisions within PMC that help to provide a more precise
      picture of the variety of signals observed within PMC. Collective data from
      anatomical, task-related fMRI and resting-state studies all indicate that the PMC
      is composed of three main regions, the precuneus, retrosplenial, and posterior
      cingulate cortex, each with a distinct function. We will conclude with a summary
      of the findings and provide directions for future research.

PMID- 22982486
TI  - Acitretin for treatment of familial porokeratosis palmaris et plantaris
      disseminate.

PMID- 22982487
TI  - Behavioural divergence, interfertility and speciation: a review.
AB  - Behavioural compatibility between mates is fundamental for maintaining species
      boundaries and is achieved through appropriate communication between males and
      females. A breakdown in communication will lead to behavioural divergence and
      reduced interfertility. In this review, we summarise the current knowledge on
      male signals and female perception of these signals, integrating the literature
      from several taxa. We advocate that signaller-perceiver coevolution, which is
      usually under strong stabilising selection to enable mating, forms the basis of
      species-specific mate recognition systems. The mechanisms (phylogeny, geography,
      ecology, biology) shaping signaller-perceiver systems are briefly discussed to
      demonstrate the factors underpinning the evolution of signaller-perceiver
      couplings. Since divergence and diversification of communication systems is
      driven by changes in the mechanical properties of sensory pathways and morphology
      of sensory organs, we highlight signal modalities (auditory, olfactory, visual,
      tactile) and their importance in communication, particularly in mate selection.
      Next, using available examples and generating a stylised model, we suggest how
      disruption (biological, ecological, stochastic) of signaller-perceiver systems
      drives behavioural divergence and consequently results in reduced interfertility
      and speciation. Future studies should adopt an integrative approach, combining
      multiple parameters (phylogeny, adaptive utility of communication systems,
      genetics and biomechanical/biochemical properties of signals and perception) to
      explore how disruption of signaller-perceiver systems results in behavioural
      divergence and reduced interfertility. Finally, we question the impact that rapid
      environmental change will have on disruption of communication systems,
      potentially interfering with signaller-perceiver couplings.

PMID- 22982488
TI  - Surfactant choice and the physical stability of nanosuspensions as a function of
      pH.
AB  - Nanosuspensions of the example compounds ketoconazole and itraconazole were shown
      to aggregate upon reducing the pH to levels comparable to that known to exist in
      the stomach. Manipulation of the surfactant/polymer ratio in the suspension
      vehicle did not elucidate the cause of the aggregation. X-ray diffraction on
      ketoconazole solids failed to identify a form change as causative. Ultimately,
      ketoconazole intrinsic dissolution rate experiments implicated surface salt
      formation between ketoconazole and the vehicle surfactant as the cause of the
      aggregation. The generality of the phenomenon is discussed.

PMID- 22982489
TI  - An engineering study on the enhanced control and operation of continuous
      manufacturing of pharmaceutical tablets via roller compaction.
AB  - A novel manufacturing strategy based on continuous processing integrated with
      online monitoring tools coupled with efficient automatic feedback control system
      is highly desired for efficient Quality by Design (QbD) based manufacturing of
      the next generation of pharmaceutical products with optimal consumption of time,
      space and resources. In this manuscript, an efficient plant-wide control strategy
      for an integrated continuous pharmaceutical tablet manufacturing process via
      roller compaction has been designed in silico. The designed control system
      consists of five cascade control loops and three single control loops resulting
      in 42 controller tuning parameters. An effective controller parameter tuning
      strategy involving an ITAE method coupled with an optimization strategy has been
      proposed and the designed control system has been implemented in a first
      principle model-based flowsheet that was simulated in gPROMS (Process System
      Enterprise). The advanced techniques (e.g. anti-windup) have been employed to
      improve the performance of the control system. The ability of the control system
      to reject the unknown disturbances as well as to track the set point has been
      analyzed. Results demonstrated enhanced performance of critical quality
      attributes (CQAs) under closed-loop control compared to open-loop operation thus
      illustrating the potential of closed-loop feedback control in improving
      pharmaceutical manufacturing operations.

PMID- 22982490
TI  - Approaches to suffering at the end of life: the use of sedation in the USA and
      Netherlands.
AB  - BACKGROUND: Studies describing physicians' experiences with sedation at the end
      of life are indispensible for informed palliative care practice, but they are
      scarce. We describe the accounts of physicians from the USA and the Netherlands,
      two countries with different regulations on end-of-life decisions regarding their
      use of sedation. METHODS: Qualitative face-to-face interviews were held in 2007
      2008 with 36 physicians (18 from the Netherlands, 18 from the USA), including
      primary care physicians and specialists. We applied purposive sampling and
      conducted constant comparative analyses. RESULTS: In both countries, the use of
      sedation was described in diverse terms, especially in the USA, and was often
      experienced as emotionally challenging. Respondents stated different and
      sometimes multiple intentions for their use of sedation. Besides alleviating
      severe suffering, most Dutch respondents justified its use by stating that it
      does not hasten death, while most American respondents indicated that it might
      hasten death but that this was justifiable as long as that was not their primary
      intention. While many Dutch respondents indicated that they initiated open
      discussions about sedation proactively to inform patients about their options and
      to allow planning, the accounts of American respondents showed fewer and less
      open discussions, mostly late in the dying process and with the patient's
      relatives. CONCLUSIONS: The justification for sedation and the openness with
      which it is discussed were found to differ in the accounts of respondents from
      the USA and the Netherlands. Further clarification of practices and research into
      the effect and effectiveness of the use of sedation is recommended to enhance
      informed reflection and policy making.

PMID- 22982491
TI  - Willingness to treat infectious diseases: what do students think?
AB  - INTRODUCTION: Outbreaks of serious communicable infectious diseases remain a
      major global medical problem and force healthcare workers to make hard choices
      with limited information, resources and time. While information regarding
      physicians' opinions about such dilemmas is available, research discussing
      students' opinions is more limited. METHODS: Medical students were surveyed about
      their willingness to perform medical procedures on patients with communicable
      diseases as students and as physicians. Students were asked about their opinions
      regarding the duty to treat in such cases. RESULTS: 74% of respondents felt that
      by deciding to enter medical school they were morally obliged to treat any
      patient despite the risks. Students' willingness to treat as physicians is
      significantly higher than their willingness to treat as students. HIV was
      significantly the most tolerated disease with respect to performing mouth to
      mouth resuscitation. Among preclinical students, we found that willingness to
      treat during the later years is significantly greater than during the earlier
      years. Among clinical students, the opposite was observed. DISCUSSION: Students'
      greater willingness to treat as physicians is mostly attributed to perceptions of
      higher obligations as a qualified doctor. There is greater but not total
      willingness to perform resuscitation on patients with HIV relative to other
      diseases. The increased willingness of preclinical students and the decreased
      willingness of clinical students both emphasise the importance of patient
      physician communication and ethics studies during medical school.

PMID- 22982492
TI  - How IRBs view and make decisions about coercion and undue influence.
AB  - INTRODUCTION: Scholars have debated how to define coercion and undue influence,
      but how institutional review boards (IRBs) view and make decisions about these
      issues in actual cases has not been explored. METHODS: I contacted the leadership
      of 60 US IRBs (every fourth one in the list of the top 240 institutions by
      National Institutes of Health funding), and interviewed 39 IRB leaders or
      administrators from 34 of these institutions (response rate=55%), and 7 members.
      RESULTS: IRBs wrestled with defining of 'coercion' and 'undue inducement', most
      notably in deciding about participant compensation. IRBs often use these terms
      synonymously and define undue inducement in varying ways, often wrestling with
      these issues, relying on 'gut feelings', and seeking compromises. Ambiguities
      arose, partly reflecting underlying tensions: whether subjects should 'get paid'
      versus 'volunteer' (ie, whether subjects should be motivated by compensation vs
      altruism), and whether subjects should be paid differently based on income, given
      possible resultant selection bias. Lack of consistent standards emerged between
      and even on single IRBs. Questions arose concerning certain aspects and types of
      studies; for example, how to view and weigh providing free care in research,
      whether and how recruitment flyers should mention compensation, and how to avoid
      coercion in paediatric, developing world, or students research. CONCLUSIONS:
      These data, the first to probe qualitatively how IRBs view and approach questions
      about coercion, undue influence and participant compensation, and to examine how
      IRBs have reviewed actual cases, reveal several critical ambiguities and
      dilemmas, and have vital implications for future practice, education, policy and
      research.

PMID- 22982494
TI  - Antimicrobial HPA3NT3 peptide analogs: placement of aromatic rings and positive
      charges are key determinants for cell selectivity and mechanism of action.
AB  - In an earlier study, we determined that HP(2-20) (residues 2-20 of parental HP
      derived from the N-terminus of the Helicobacter pylori ribosomal protein L1) and
      its analog, HPA3NT3, had potent antimicrobial effects. However, HPA3NT3 also
      showed undesirable cytotoxicity against HaCaT cells. In the present study, we
      designed peptide analogs including HPA3NT3-F1A (-F1A), HPA3NT3-F8A (-F8A),
      HPA3NT3-F1AF8A (-F1AF8A), HPA3NT3-A1 (-A1) and HPA3NT3-A2 (-A2) in an effort to
      investigate the effects of amino acid substitutions in reducing their
      hydrophobicity or increasing their cationicity, and any resulting effects on
      their selectivity in their interactions with human cells and pathogens, as well
      as their mechanism of antimicrobial action. With the exception of HPA3NT3-A1, all
      of these peptides showed potent antimicrobial activity. Moreover, substitution of
      Ala for Phe at positions 1 and/or 8 of the HPA3NT3 peptides (-F1A, -F8A and 
      F1AF8A) dramatically reduced their cytotoxicity. Thus the cytotoxicity of HPA3NT3
      appears to be related to its Phe residues (positions 1 and 8), which strongly
      interact with sphingomyelin in the mammalian cell membrane. HPA3NT3 exerted its
      bactericidal effects through membrane permeabilization mediated by pore
      formation. In contrast, fluorescent dye leakage and nucleic acid gel retardation
      assays showed that -A2 acted by penetrating into the cytoplasm, where it bound to
      nucleic acids and inhibited protein synthesis. Notably, Staphylococcus aureus did
      not develop resistance to -A2 as it did with rifampin. These results suggest that
      the -A2 peptide could potentially serve as an effective antibiotic agent against
      multidrug-resistant bacterial strains.

PMID- 22982495
TI  - Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of
      membrane targeting.
AB  - The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created
      the need for better therapeutic options. In this study, five natural xanthones
      were extracted and purified from the fruit hull of Garcinia mangostana and their
      antimicrobial properties were investigated. alpha-Mangostin was identified as the
      most potent among them against Gram-positive pathogens (MIC=0.78-1.56 MUg/mL)
      which included two MRSA isolates. alpha-Mangostin also exhibited rapid in vitro
      bactericidal activity (3-log reduction within 5 min). In a multistep (20 passage)
      resistance selection study using a MRSA isolated from the eye, no resistance
      against alpha-mangostin in the strains tested was observed. Biophysical studies
      using fluorescence probes for membrane potential and permeability, calcein
      encapsulated large unilamellar vesicles and scanning electron microscopy showed
      that alpha-mangostin rapidly disrupted the integrity of the cytoplasmic membrane
      leading to loss of intracellular components in a concentration-dependent manner.
      Molecular dynamic simulations revealed that isoprenyl groups were important to
      reduce the free energy for the burial of the hydrophobic phenyl ring of alpha
      mangostin into the lipid bilayer of the membrane resulting in membrane breakdown
      and increased permeability. Thus, we suggest that direct interactions of alpha
      mangostin with the bacterial membrane are responsible for the rapid concentration
      dependent membrane disruption and bactericidal action.

PMID- 22982496
TI  - Membrane composition influences the topology bias of bacterial integral membrane
      proteins.
AB  - Small multidrug resistance (SMR) protein family members confer bacterial
      resistance to toxic antiseptics and are believed to function as dual topology
      oligomers. If dual topology is essential for SMR activity, then the topology bias
      should change as bacterial membrane lipid compositions alter to maintain a
      "neutral" topology bias. To test this hypothesis, a bioinformatic analysis of
      bacterial SMR protein sequences was performed to determine a membrane protein
      topology based on charged amino acid residues within loops, and termini regions
      according to the positive inside rule. Three bacterial lipid membrane parameters
      were examined, providing the proportion of polar lipid head group charges at the
      membrane surface (PLH), the relative hydrophobic fatty acid length (FAL), and the
      proportion of fatty acid unsaturation (FAU). Our analysis indicates that
      individual SMR pairs, and to a lesser extent SMR singleton topology biases, are
      significantly correlated to increasing PLH, FAL and FAU differences validating
      the hypothesis. Correlations between the topology biases of SMR proteins
      identified in Gram+ compared to Gram- species and each lipid parameter
      demonstrated a linear inverse relationship.

PMID- 22982493
TI  - Ca(V)1.1: The atypical prototypical voltage-gated Ca2+ channel.
AB  - Ca(V)1.1 is the prototype for the other nine known Ca(V) channel isoforms, yet it
      has functional properties that make it truly atypical of this group.
      Specifically, Ca(V)1.1 is expressed solely in skeletal muscle where it serves
      multiple purposes; it is the voltage sensor for excitation-contraction coupling
      and it is an L-type Ca2+ channel which contributes to a form of activity
      dependent Ca2+ entry that has been termed Excitation-coupled Ca2+ entry. The
      ability of Ca(V)1.1 to serve as voltage-sensor for excitation-contraction
      coupling appears to be unique among Ca(V) channels, whereas the physiological
      role of its more conventional function as a Ca2+ channel has been a matter of
      uncertainty for nearly 50 years. In this chapter, we discuss how Ca(V)1.1
      supports excitation-contraction coupling, the possible relevance of Ca2+ entry
      through Ca(V)1.1 and how alterations of Ca(V)1.1 function can have
      pathophysiological consequences. This article is part of a Special Issue
      entitled: Calcium channels.

PMID- 22982497
TI  - Effect of Azadinium spinosum on the feeding behaviour and azaspiracid
      accumulation of Mytilus edulis.
AB  - Azadinium spinosum, a small toxic dinoflagellate, was recently isolated and
      identified as a primary producer of azaspiracid toxins (AZAs). Previous
      experiments related to AZA accumulation in blue mussels upon direct feeding with
      A. spinosum revealed increased mussel mortality and had negative effects on the
      thickness of the digestive gland tubules. Therefore we conducted follow up
      experiments in order to study effects of A. spinosum on mussel feeding behaviour.
      Individual assessment of mussel feeding time activity (FTA), clearance rate (CR),
      filtration rate (TFR), absorption rate (AR), faeces and pseudofaeces production
      were carried out on mussel fed either toxic (A. spinosum) or non-toxic
      (Isochrisis aff. galbana (T-Iso)) diets. Furthermore, AZA accumulation and
      biotransformation in mussels were followed using liquid chromatography coupled to
      tandem mass spectrometry (LC-MS/MS). A. spinosum had a significant effect on
      mussel feeding behaviour compared to T-Iso: CR was lower by a factor of 6, FTA by
      a factor of 5, TFR by a factor of 3 and AR even decreased to negative values for
      the last day of exposure. Even so, a rapid AZA accumulation was observed during
      the first hours of the trial; less than 6h of feeding were required to reach AZA
      concentration in mussel above regulatory level. In consistence with physiological
      observations, AZA concentration of about 200 MUg kg(-1) did not increase further
      until the end of the study. AZA bioconversion was also found to be a fast
      process: after 3h of exposure AZA17, -19 and AZA7-10 were already found, with a
      proportion of AZA17 equal to AZA2. These results show a negative effect of A.
      spinosum on blue mussel feeding activity and indicate a possible regulation of
      AZA uptake by decreasing filtration and increasing pseudofaeces production.

PMID- 22982498
TI  - Estrogen receptor-hijacking by dioxin-like 3,3'4,4',5-pentachlorobiphenyl
      (PCB126) in salmon hepatocytes involves both receptor activation and receptor
      protein stability.
AB  - Several hypotheses have been proposed explaining the interactions between
      estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) signaling pathways in
      both fish and mammalian systems. In both piscine and mammalian systems, ligand
      activated AhR may recruit basal ER (i.e. hijack) in the absence of ER ligand and
      bind to the estrogen responsive elements (ERE) to activate ER-responsive genes.
      We have evaluated, the roles of receptor activation and receptor-protein
      stability on dioxin-like [3,3'4,4',5-pentachlorobiphenyl: PCB 126] mediated ER
      hijacking in a salmon in vitro system. Primary salmon hepatocytes were exposed to
      PCB126 (1, 10 and 50 nM) with or without an ER-antagonist (ICI), putative AhR
      inhibitor (3',4'-dimethoxyflavone; DMF) or protein synthesis inhibitor
      (cycloheximide; CHX). Hepatocytes were exposed for 6, 12 and 24h. The expression
      of genes and proteins involved in ER (ERalpha, ERbeta and vitellogenin) and AhR
      (CYP1A1, AhR-repressor, AhR2-isotypes and cofactors) pathways were analysed using
      qPCR and immunochemical methods. PCB126 induced transcripts of ER and AhR
      signalling pathways that were variably influenced by protein synthesis and
      receptor inhibitors. CHX stimulated a coordinated recruitment of the proteasome
      complex, resulting in the ubiquitination and degradation of ER and AhR isoforms
      and downstream protein products. Interestingly, DMF produced differential effects
      on the AhR signalling pathway, in the presence or absence of PCB126. Overall, ER
      hijacking by dioxin-like compounds and subsequent activation of ER responsive
      genes involves both receptor activation/deactivation and receptor-protein
      degradation/destabilization (stability). Given that the Per-AhR/Arnt-Sim homology
      sequence of transcription factors usually associate with each other to form
      heterodimers and bind the XRE or ERE sequences in the promoter regions of target
      genes to regulate their expression, the complete mechanism of interactions
      between dioxin-like and estrogenic compounds in vertebrate systems may require
      additional characterization.

PMID- 22982499
TI  - Toxicity of atrazine and nonylphenol in juvenile rainbow trout (Oncorhynchus
      mykiss): effects on general health, disease susceptibility and gene expression.
AB  - Atrazine (ATZ) and nonylphenol (NP) are commonly identified contaminants in
      aquatic habitats; however, few studies have considered the impact of these
      endocrine disrupters on immune function and resistance to disease. This study
      examined the immunotoxicological effects of ATZ and NP at multiple levels of
      biological organization. Juvenile rainbow trout (Oncorhynchus mykiss) were
      exposed to a solvent control (0.00625%, v/v anhydrous ethanol), or sub-lethal
      concentrations of ATZ (59 MUg/L and 555 MUg/L) or NP (2.3 MUg/L or 18 MUg/L) for
      4d. At the end of exposure, fish were assessed for a number of physiological
      endpoints, including a host resistance challenge, and liver gene expression was
      assessed using a salmonid microarray (cGRASP, 32K version 1). While the low ATZ
      and low NP treatments had no measurable effects on the physiological endpoints
      measured, fish exposed to the high ATZ concentration (555 MUg/L) exhibited
      significantly elevated plasma cortisol, a decrease in SSI, and decreased
      lymphocytes and increased monocytes in peripheral blood, with suppression of
      early immune system processes apparent at the molecular level. In contrast, fish
      exposed to the high NP concentration (18 MUg/L) showed physiological (e.g.
      significantly elevated LSI) and gene expression changes (e.g. induction of
      vitellogenin) consistent with estrogenic effects, as well as decreased
      lymphocytes in the peripheral blood and more limited alterations in immune system
      related pathways in the liver transcriptome. Fish exposed to high ATZ or NP
      concentrations incurred higher mortality than control fish following a disease
      challenge with Listonella anguillarum, while fish exposed to the lower
      concentrations were unaffected. Microarray analysis of the liver transcriptome
      revealed a total of 211 unique, annotated differentially regulated genes (DRGs)
      following high ATZ exposure and 299 DRGs following high NP exposure. Functional
      (enrichment) analysis revealed effects on immune system function, metabolism,
      oxygen homeostasis, cell cycle, DNA damage, and other processes affected by ATZ
      or NP exposure. Overall, this study provides evidence at multiple levels of
      biological organization that both ATZ and NP are immunotoxic at sub-lethal
      concentrations and highlights the potential risk posed by these chemicals to wild
      fish populations.

PMID- 22982500
TI  - Estimating the capability of microalgae to physiological acclimatization and
      genetic adaptation to petroleum and diesel oil contamination.
AB  - There is increasing scientific interest in how phytoplankton reacts to petroleum
      contamination, since crude oil and its derivatives are generating extensive
      contamination of aquatic environments. However, toxic effects of short-term
      petroleum exposure are more widely known than the adaptation of phytoplankton to
      long-term petroleum exposure. An analysis of short-term and long-term effects of
      petroleum exposure was done using experimental populations of freshwater
      (Scenedesmus intermedius and Microcystis aeruginosa) and marine (Dunaliella
      tertiolecta) microalgae isolated from pristine sites without crude oil product
      contamination. These strains were exposed to increased levels of petroleum and
      diesel oil. Short-term exposure to petroleum or diesel oil revealed a rapid
      inhibition of photosynthetic performance and cell proliferation in freshwater and
      marine phytoplankton species. A broad degree of inter-specific variation in
      lethal contamination level was observed. When different strains were exposed to
      petroleum or diesel oil over the long-term, the cultures showed massive
      destruction of the sensitive cells. Nonetheless, after further incubation, some
      cultures were able to grow again due to cells that were resistant to the toxins.
      By means of a fluctuation analysis, discrimination between cells that had become
      resistant due to physiological acclimatization and resistant cells arising from
      rare spontaneous mutations was accomplished. In addition, an analysis was done as
      to the maximum capacity of adaptation to a gradual contamination process. An
      experimental ratchet protocol was used, which maintains a strong selection
      pressure in a temporal scale up to several months over very large experimental
      populations of microalgae. Microalgae are able to survive to petroleum
      contamination as a result of physiological acclimatization without genetic
      changes. However, when petroleum concentration exceeds the physiological limits,
      survival depends exclusively on the occurrence on mutations that confer
      resistance and subsequent selection of these mutants. Finally, it is certain that
      further mutations and selection will ultimately determine adaptation of
      microalgae to the environmental forcing.

PMID- 22982501
TI  - Dose- and time-related changes in aerobic metabolism, chorionic disruption, and
      oxidative stress in embryonic medaka (Oryzias latipes): underlying mechanisms for
      silver nanoparticle developmental toxicity.
AB  - Silver nanoparticles (AgNPs) are widely employed in commercial products, and are
      thus inevitably released into the aquatic environment. Many studies have
      indicated that AgNPs could induce toxicological effects on embryonic fish. To
      understand the mechanism of AgNP developmental toxicity, we determined the
      effects of AgNPs on the egg membrane, aerobic metabolism, antioxidant system,
      lipid peroxidation, as well as reactive oxygen species (ROS) and singlet oxygen
      ((1)O(2)) generation in early-life medaka fish (Oryzias latipes). AgNP treatment
      at 62.5-1000 MUg/L caused significant increase in retarded development and
      abnormalities. Destruction of the surface ornamentation and egg envelope was
      observed at a higher AgNP concentration (>=125 MUg/L) using light microscopy and
      scanning electron microscopy. A dose-dependent increase in lactate dehydrogenase
      activity, an indicator of anaerobic metabolism, and superoxide dismutase activity
      was observed in the treated embryos. In contrast, the total reduced glutathione
      level decreased. A high thiobarbituric acid reactive substance concentration was
      generated upon AgNP exposure from day 1 to day 7 postfertilisation. The
      biochemical parameters suggested that oxidative stress was induced by the AgNPs.
      Unexpectedly, a dose-dependent reduction in ROS and (1)O(2) generation upon high
      AgNP exposure (>=250 MUg/L) was observed. Although the morphological damages
      induced by the AgNPs were irreversible, restorable antioxidant defenses were
      noted in the well-developed embryos. This finding supported the idea that the
      stage of morphogenesis and organogenesis is a critical window to chemical
      exposure or environmental stress. Overall, the results suggested that hypoxia,
      disturbed egg chorion, and oxidative stress are mechanistically associated with
      AgNP toxicity in embryonic fish.

PMID- 22982502
TI  - N(1)-(quinolin-2-ylmethyl)butane-1,4-diamine, a polyamine analogue, attenuated
      injury in in vitro and in vivo models of cerebral ischemia.
AB  - It has been widely recognized that glutamate (Glu)-induced cytotoxicity,
      intracellular calcium overload and excessive free radical production are the key
      players in the development and progression of ischemic brain injury. Since MK
      801, an antagonist of N-methyl-d-aspartate (NMDA) receptor, showed many adverse
      reactions that hampered its clinical applications, development of safe and
      effective agent for the treatment of cerebral ischemia is eagerly required. This
      study was to investigate the effects of N(1)-(quinolin-2-ylmethyl)butane-1,4
      diamine (QMA), a polyamine analogue, on the in vitro and in vivo models of
      cerebral ischemic damage. The results revealed that pretreatment with QMA could
      attenuate Glu, putrescine (Put) and oxygen-glucose deprivation (OGD)-induced cell
      death, lipid peroxidation as well as the elevation of reactive oxygen species
      (ROS) and intracellular [Ca(2+)](i) in pheochromocytoma (PC12) cells and in rat
      primary cortical neurons. The results also demonstrated that QMA could inhibit
      NMDA-mediated intracellular [Ca(2+)](i) accumulation in rat primary cortical
      neurons and reduce brain infarct volume in middle cerebral artery occlusion
      (MCAO) rats. The present report suggested that polyamines played a crucial role
      in the pathological processes of cerebral ischemic damage and that QMA or other
      novel polyamine analogues could be promising therapeutic candidates for stroke by
      virtue of their anti-hypoxia and antioxidation property.

PMID- 22982503
TI  - Prepubertal exposure to glucocorticoid delays puberty independent of the
      hypothalamic Kiss1-GnRH system in female rats.
AB  - Secretion of glucocorticoids is widely known as a key endocrine response to
      stresses. Prenatal dexamethasone administration induces intrauterine growth
      retardation and delayed onset of puberty in female rats independent of the
      hypothalamic Kiss1-gonadotropin-releasing hormone (GnRH) system. The aim of this
      study was to evaluate the influence of chronic intracerebroventricular (central,
      CD) or subcutaneous (peripheral, PD) dexamethasone administration to prepubertal
      female rats on the onset of puberty and body weight change. Rats administered
      dexamethasone from day 25 to day 34 (CD and PD) showed significantly reduced body
      weight gain throughout the experimental period and delayed onset of vaginal
      opening compared with rats administered saline centrally (CS) or peripherally
      (PS). At 34 days old, hypothalamic Kiss1r mRNA levels were significantly lower
      with CD than with CS. No significant differences were seen between rats
      administered saline and rats administered dexamethasone with regard to
      hypothalamic Kiss1, GnRH and NPY mRNA levels or serum LH levels. Serum leptin
      concentrations were higher in CD and PD than in the controls (CS and PS). These
      results suggest that the delayed onset of puberty induced by prepubertal
      dexamethasone administration occurs independent of the hypothalamic Kiss1-GnRH
      system.

PMID- 22982504
TI  - Steroid hormones specifically modify the activity of organic anion transporting
      polypeptides.
AB  - Previously, the steroid hormone progesterone has been demonstrated to stimulate
      OATP2B1-mediated transport of estrone-3-sulphate (E(1)S), dehydroepiandrosterone
      sulphate (DHEAS) and pregnenolone sulphate (PS), which may influence the uptake
      of precursor molecules for steroid hormone synthesis. However, it is unclear
      whether OATP2B1 drug substrates like atorvastatin or glibenclamide are also
      affected by this phenomenon. In addition, it has not been studied so far if this
      stimulatory effect is specific for OATP2B1. To address these questions, we
      examined the influence of progesterone on OATP2B1-mediated atorvastatin and
      glibenclamide uptake and studied the impact of steroid hormones on the transport
      activity of OATP1A2, OATP1B1 and OATP1B3. Comparison of the substrate spectrum of
      the investigated OATPs revealed that DHEAS and atorvastatin are substrates of all
      transporters, while E(1)S was only significantly transported by OATP1A2, OATP2B1
      and OATP1B1. Glibenclamide uptake was limited to OATP1A2, OATP1B1 and OATP2'B1.
      Subsequent interaction studies indicated that progesterone only increases OATP2B1
      mediated E(1)S and DHEAS transport, whereas uptake of BSP, atorvastatin and
      glibenclamide was either inhibited or not affected. Moreover, the steroid hormone
      effect was specific for OATP2B1; neither OATP1B1, OATP1B3 nor OATP1A2 function
      was stimulated in the presence of progesterone. Similar to progesterone, the
      glucocorticoide dexamethasone stimulated OATP2B1-mediated transport of E(1)S and
      DHEAS (EC(50) for E(1)S: 10.2 +/- 5.6 MUM and 17.9 +/- 15.4 MUM for DHEAS). In
      conclusion, our data demonstrate that among the tested compounds the stimulatory
      effect of progesterone is specific for OATP2B1 and restricted to sulphated
      steroids like E(1)S and DHEAS while the OATP-mediated drug transport is not
      enhanced.

PMID- 22982506
TI  - A mass spectrometric method for quantifying C3 and C6 phosphorylation of starch.
AB  - The glucosyl residues comprising starch can be phosphorylated at either the C3 or
      the C6 position of the molecule because of the activities of two distinct
      dikinase enzymes. After hydrolysis of the starch, the C6 phosphorylation is easy
      to measure using a routine enzyme assay for glucose 6-phosphate, but the C3
      phosphorylation is more difficult to assay. A mass spectrometric (MS) method has
      been developed that, in a single run, can distinguish and quantify the glucose 3
      phosphate and glucose 6-phosphate produced by hydrolysis of starch and can also
      measure the glucose content to give an accurate estimate of the starting
      material. The MS method involves quantification by LC/MS with external standards,
      using normal-phase hydrophilic interaction liquid chromatography and selective
      reaction monitoring. The MS method has been used to determine degrees of starch
      phosphorylation in a diverse group of potato lines, revealing threefold
      differences in phosphorylation between high- and low-phosphate lines. The method
      was also used to show that cold storage of potato tubers for up to 24weeks had
      little substantive effect on the levels of starch phosphorylation. MS provided an
      effective and efficient means of determining both the C6 and the C3
      phosphorylation of starch.

PMID- 22982505
TI  - Method for microRNA isolation from clinical serum samples.
AB  - MicroRNAs are a group of intracellular noncoding RNA molecules that have been
      implicated in a variety of human diseases. Because of their high stability in
      blood, microRNAs released into circulation could be potentially utilized as
      noninvasive biomarkers for diagnosis or prognosis. Current microRNA isolation
      protocols are specifically designed for solid tissues and are impractical for
      biomarker development utilizing small-volume serum samples on a large scale.
      Thus, a protocol for microRNA isolation from serum is needed to accommodate these
      conditions in biomarker development. To establish such a protocol, we developed a
      simplified approach to normalize sample input by using single synthetic spike-in
      microRNA. We evaluated three commonly used commercial microRNA isolation kits for
      the best performance by comparing RNA quality and yield. The manufacturer's
      protocol was further modified to improve the microRNA yield from 200MUl of human
      serum. MicroRNAs isolated from a large set of clinical serum samples were tested
      on the miRCURY LNA real-time PCR panel and confirmed to be suitable for high
      throughput microRNA profiling. In conclusion, we have established a proven method
      for microRNA isolation from clinical serum samples suitable for microRNA
      biomarker development.

PMID- 22982507
TI  - Specific detection of N-glycolylneuraminic acid and Galalpha1-3Gal epitopes of
      therapeutic antibodies by partial-filling capillary electrophoresis.
AB  - The oligosaccharide structure is very important in biopharmaceuticals because of
      its effects on protein function, including efficacy and half-life. N
      glycolylneuraminic acid (Neu5Gc) and Galalpha1-3Gal (alpha-Gal) residues are
      known to show immunogenicity in humans. It is now understood that murine cell
      lines, such as NS0 or SP2, which are typically used for biopharmaceutical
      manufacture, produce proteins containing Neu5Gc and alpha-Gal residues. The
      expression of these specific residues is affected by the cell line and culture
      conditions. Therefore, monitoring and controlling the levels of these epitopes
      are important for the quality control of biopharmaceuticals. To detect the two
      epitopes on a therapeutic antibody produced by NS0 cells, we applied partial
      filling capillary electrophoresis using anti-Neu5Gc antibody and alpha
      galactosidase. In the anti-Neu5Gc antibody filling method, one minor glycan peak
      with Neu5Gc residues at the nonreducing end disappeared specifically from the
      electropherogram. In the alpha-galactosidase filling method, some minor peaks
      with alpha1,3-linked Gal residues disappeared. However, in a therapeutic antibody
      from Chinese hamster ovary cells, no peaks disappeared with the two methods.
      These results show this method can be used to specifically detect and quantify
      the two epitopes on biopharmaceuticals with high sensitivity.

PMID- 22982508
TI  - A direct extraction method for microRNAs from exosomes captured by immunoaffinity
      beads.
AB  - A direct extraction method was developed for exosomal microRNAs. After isolation
      of exosomes from human serum by immunoaffinity magnetic beads, microRNAs were
      extracted by just mixing beads with a lysis solution and heating without further
      purification. The lysis solution was composed of a nonionic detergent and salt
      (NaCl). The concentration of each component was optimized to maximize lysis
      efficiency and to inhibit adsorption of extracted microRNAs on beads. MicroRNAs
      extracted by this method could be quantitatively analyzed by qRT-PCR, indicating
      that the method could replace conventional methods for extracting microRNAs from
      immunobead-captured exosomes.

PMID- 22982509
TI  - Organism-induced habitat restoration leads to bi-stability in metapopulations.
AB  - Following Levins' patch occupancy model, we presented a differential-equation
      model, in which both the metapopulation dynamics and the dynamics of the fraction
      of suitable patches in the habitat are characterized. Habitat restoration induced
      by organism itself (internal restoration) and by other organisms or/and abiotic
      causes (external restoration) were incorporated in the model, together with
      habitat destruction. Stability analysis revealed the existence of alternative
      equilibriums (i.e., bi-stability) in the system. The internal restoration of
      habitat was identified as the trigger for the bi-stability, whereas the external
      restoration, in contrast, can eliminate the bi-stability from the system. The
      results, thus, emphasize the important role of the organism-environment feedback
      in biological conservation.

PMID- 22982510
TI  - Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced
      oxidative stress and activation of nuclear factor Kappa-B in rats.
AB  - Pulmonary fibrosis is one of the most common chronic interstitial lung diseases
      with high mortality rate after diagnosis and limited successful treatment. The
      present study was designed to assess the potential antifibrotic effect of
      thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress
      and inflammatory response during bleomycin-induced pulmonary fibrosis. Male
      Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3
      times a week for 4 weeks) and/or thymoquinone (5mg/kg/day, 1 week before and
      until the end of the experiment). Bleomycin significantly increased lung weight
      and the levels of Lactate dehydrogenase, total leucocytic count, total protein
      and mucin in bronchoalveolar lavage and these effects were significantly
      ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a
      significant increase in the levels of lipid peroxides and nitric oxide
      accompanied with a significant decrease in the antioxidant enzyme activity of
      superoxide dismutase and glutathione transferase. TQ treatment restored these
      markers toward normal values. TQ also counteracted emphysema in air alveoli,
      inflammatory cell infiltration, lymphoid hyperplastic cells activation
      surrounding the bronchioles and the over expression of activated form of nuclear
      factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was
      assessed by measuring hydroxyproline content, which increased markedly in the
      bleomycin group and significantly reduced by concurrent treatment with TQ.
      Furthermore, histopathological examination confirmed the antifibrotic effect of
      TQ. Collectively these findings indicate that TQ has potential antifibrotic
      effect beside its antioxidant activity that could be through NF-kappaB
      inhibition.

PMID- 22982511
TI  - Reactive oxygen species (ROS) and sensitization to TRAIL-induced apoptosis, in
      Bayesian network modelling of HeLa cell response to LY303511.
AB  - BACKGROUND: The compound LY303511 (LY30) has been proven to induce production of
      ROS and to sensitize cancer cells to TRAIL-induced apoptosis, but the mechanisms
      and mediators of LY30-induced effects are potentially complex. Bayesian networks
      are a modelling technique for making probabilistic inferences about complex
      networks of uncertain causality. METHODS: Fluorescent indicators for ROS,
      reactive nitrogen species (RNS), and free calcium were measured in time-series
      after LY30 treatment. This "correlative" dataset was used as input for Bayesian
      modelling to predict the causal dependencies among the measured species.
      Predictions were compared against a separate "causal" dataset, in which cells had
      been treated with FeTPPS to scavenge peroxynitrite, EGTA-am to chelate calcium,
      and Tiron to scavenge O(2)(-). Finally, cell viability measurements were
      integrated into an extended model of LY30 effects. RESULTS: LY30 treatment caused
      a rapid increase of ROS (measured by DCFDA) as well as a significant increase in
      RNS and calcium. Bayesian modelling predicted that Ca(2+)was a partial cause of
      the ROS induced by short incubations with LY30, and that RNS was strongly
      responsible for the ROS induced by long incubations with LY30. Validation
      experiments confirmed the predicted roles of RNS and calcium, and also
      demonstrated a causal role for O(2)(-). In cell viability experiments, the
      additive effects of calcium and peroxynitrite were responsible for 90% of LY30
      mediated sensitization to TRAIL-induced apoptosis. CONCLUSIONS: We conclude that
      LY30 induces interdependent pathways of reactive species and stress signalling,
      with peroxynitrite and calcium contributing most significantly to apoptosis
      sensitization.

PMID- 22982512
TI  - Discourse production following injury to the dorsolateral prefrontal cortex.
AB  - Individuals with damage to the prefrontal cortex, and the dorsolateral prefrontal
      cortex (DLPFC) in particular, often demonstrate difficulties with the formulation
      of complex language not attributable to aphasia. The present study employed a
      discourse analysis procedure to characterize the language of individuals with
      left (L) or right (R) DLPFC lesions. All participants were 30-35 years post-onset
      of injury and presented with persistent discourse impairments. The discourse
      performance of the R DLPFC group was not significantly different from either the
      L DLPFC group or the non-injured comparison group. Individuals from the L DLPFC
      group demonstrated specific difficulties with narrative coherence and inclusion
      of critical story components. Both measures were significantly different from the
      comparison group. The discourse ability of the DLPFC groups was significantly
      correlated with measures of working memory. Findings support the use of discourse
      analysis for examining language impairments in individuals with PFC lesions.

PMID- 22982513
TI  - "How to do things with words": role of motor cortex in semantic representation of
      action words.
AB  - Language, believed to have originated from actions, not only functions as a
      medium to access other minds, but it also helps us commit actions and enriches
      our social life. This fMRI study investigated the semantic and neural
      representations of actions and mental states. We focused mainly on language
      semantics (comprehending sentences with action words versus those with mental
      state words). While in an fMRI scanner, twenty-four healthy, right-handed adult
      volunteers read a series of sentences with a verb depicting either a mental state
      (e.g., deceive, persuade) or an action (e.g., punch, kick), and answered a
      comprehension question that followed. Overall, this task showed brain activation
      in the left inferior frontal gyrus and in the left posterior superior temporal
      sulci. While comprehending sentences with mental state terms, participants showed
      greater activation in left orbitofrontal, and in left precuneus areas. On the
      other hand, the action sentences recruited more primary motor, left inferior
      parietal, bilateral occipital, right superior temporal, and right inferior
      frontal areas. The findings of this study underscore the role of motor and
      visuospatial involvement in action word representation in the human brain.

PMID- 22982515
TI  - Acute psychosocial stress differentially influences salivary endocrine and immune
      measures in undergraduate students.
AB  - Undergraduate students routinely experience acute psychosocial stress when
      interviewing for post-collegiate employment. While numerous studies have
      demonstrated that acute stress can increase release of immune-relevant molecules
      in blood, fewer studies have examined if acute stress also increases immune
      relevant molecules into saliva. Saliva, and the biomolecules found in saliva
      often serve important immune defense roles and can be used to non-invasively
      screen for many systemic diseases. Therefore, the current study examined saliva
      concentrations of endocrine and immune molecules following exposure to an acute
      psychosocial stressor (mock job interview) in undergraduates. Heart rate, blood
      pressure, salivary cortisol, salivary immunoglobulin-A (S-IgA), and salivary C
      reactive protein (S-CRP) were compared in healthy college undergraduates (n=15)
      before and after completion of the Trier Social Stress Test (TSST). The TSST
      induced significant increases in heart rate, systolic blood pressure, and
      salivary cortisol. Additional analyses revealed a non-significant (p=0.1)
      increase in the level of S-IgA following the TSST. A significant decrease in S
      IgA was observed during the recovery period. No change in S-CRP was observed
      following the TSST. These results suggest that acute stress experienced by
      undergraduates when interviewing for a job activates the sympathetic nervous
      system and hypothalamic-pituitary-adrenal axis and that cortisol levels increase
      in saliva. Stress-induced elevations in cortisol might be responsible for the
      decreased S-IgA observed following the recovery period. Collectively, these data
      provide further insight into the interaction between psychosocial stress,
      endocrine, and immune functioning.

PMID- 22982514
TI  - Isolation rearing attenuates social interaction-induced expression of immediate
      early gene protein products in the medial prefrontal cortex of male and female
      rats.
AB  - Early life adversity and stress in humans have been related to a number of
      psychological disorders including anxiety, depression, and addiction. The present
      study used isolation rearing, a well-characterized animal model of early life
      adversity, to examine its effects on social behavior and immediate early gene
      (IEG) expression produced by exposure to a novel social experience. Male and
      female rats were housed in same-sex groups or in isolation for 4 weeks beginning
      at weaning and were tested during late adolescence. The protein products of the
      IEGs c-fos and Arc, as well as the neurotrophic factor BDNF were assessed in
      medial prefrontal cortex (mPFC) subregions (anterior cingulate, prelimbic and
      infralimbic) using immunohistochemistry. Aggressive and non-aggressive behaviors
      during novel social exposure were also assessed. Exposure to a novel conspecific
      produced increases in Arc and c-fos activation in the mPFC of group reared
      animals in a sex- and subregion-dependent fashion compared to no social exposure
      controls, but this increase was blunted or absent in isolated animals. Isolates
      engaged in more social interactions and more aggressive behavior than group
      reared rats. Sex differences in some behaviors as well as in Arc and BDNF
      expression were observed. These results indicate that isolation rearing alters
      IEG activation in the mPFC produced by exposure to a novel conspecific, in
      addition to changing social behavior, and that these effects depend in part on
      sex.

PMID- 22982516
TI  - A propionate-inducible expression system based on the Corynebacterium glutamicum
      prpD2 promoter and PrpR activator and its application for the redirection of
      amino acid biosynthesis pathways.
AB  - A novel expression system for Corynebacterium glutamicum, based on the
      transcriptional activator of propionate metabolism genes PrpR and its target
      promoter/operator sequence, was developed and tested. The activator PrpR is co
      activated by propionate added to the growth medium. In a minimal medium a
      propionate concentration of only 1 mg l-1 was found to be sufficient for full
      induction (up to 120-fold) of its native target, the propionate metabolism operon
      prpDBC2. Then, an artificial transcription and translation reporter system, using
      the cat gene encoding chloramphenicol acetyl transferase was constructed and
      tested. The induction was found to be as fast and as high as in the natural
      system, reaching its maximal transcriptional induction rate within 2 min and a
      significant accumulation of Cat protein at around 30 min. The duration of the
      induced transcription was found to be controllable by the propionate
      concentration applied. The prpD2 promoter and PrpR activator based expression
      system revealed very similar characteristics in minimal and complex media, making
      it ideal for applications in large scale industrial fermentations. As a proof-of
      principle, the expression system was employed for the propionate-inducible
      redirection of metabolites in a lysine-production C. glutamicum strain at the
      homoserine dehydrogenase (hom) branching point, which resulted in an up to 2.5
      fold increase of the concentrations of the three amino acids (threonine,
      homoserine and isoleucine) in the supernatant.

PMID- 22982517
TI  - Bacterial microcompartments moving into a synthetic biological world.
AB  - Bacterial microcompartments are proteinaceous organelles that are found in a
      broad range of bacteria. They are composed of an outer protein shell that encases
      a specific metabolic process. Examples include the carboxysome, which houses
      enzymes associated with carbon fixation, and the propanediol metabolosome, which
      contains enzymes linked with the catabolism of propanediol to propionic acid. In
      this article the molecular structure of bacterial microcompartments is examined
      and the potential to engineer these intriguing organelles for biotechnological
      applications is explored.

PMID- 22982518
TI  - Biomechatronics for designing bioprocess monitoring and control systems:
      application to stem cell production.
AB  - Stem cell production systems need elaborate monitoring and control for meeting
      requirements on the final cell product. In this article, the use of
      biomechatronic design methodology for supporting these efforts is described.
      Biomechatronic design, which is based on a fundamental systematical design
      approach originating from mechanical engineering, is here applied for
      investigating how monitoring and control systems can be configured in stem cell
      manufacturing processes. Results are provided that demonstrate how the
      biomechatronic design tools are used to compare different process analytical
      instrumentation resulting in a design layout for the monitoring system for
      derivation of hepatocytes from human embryonic stem cells. The results can be
      extrapolated to other stem cell production processes using the same methodology.

PMID- 22982519
TI  - Trait anxiety and post-learning stress do not affect perceptual learning.
AB  - While it is well established that stress can modulate declarative learning, very
      few studies have investigated the influence of stress on non-declarative
      learning. Here, we studied the influence of post-learning stress, which
      effectively modulates declarative learning, on perceptual learning of a visual
      texture discrimination task (TDT). On day one, participants trained for one
      session with TDT and were instructed that they, at any time, could be exposed to
      either a high stressor (ice-water; Cold Pressor Test; CPT) or a low stressor
      (warm water). Participants did not know when or which stressor they would be
      exposed to. To determine the impact of the stressor on TDT learning, all
      participants returned the following day to perform another TDT session. Only
      participants exposed to the high stressor had significantly elevated cortisol
      levels. However, there was no difference in TDT improvements from day one to day
      two between the groups. Recent studies suggested that trait anxiety modulates
      visual perception under anticipation of stressful events. Here, trait anxiety did
      neither modulate performance nor influence responsiveness to stress. These
      results do not support a modulatory role for stress on non-declarative perceptual
      learning.

PMID- 22982520
TI  - ELISA rescue protocol: recovery of sample concentrations from an assay with an
      unsuccessful standard curve.
AB  - The Enzyme-linked Immunosorbant Assay (ELISA) is a method commonly used to
      measure proteins in various biological matrices, due to its ease of performance
      and relatively low cost. In order for quantitative data to be generated, a
      reference standard curve must be prepared for each assay; however, due to
      investigator error or standard protein degradation, otherwise representative
      experimental sample data are rendered useless. Herein, we describe a protocol by
      which sample concentrations can be recovered from assays in which the standard
      curve fails. The DeltaOD values of the experimental samples are used to generate
      a new standard curve, which is applied back to the original plate. For validation
      of this method, experimental sample concentrations obtained using acceptable
      standard curves were potted against those calculated using this new method. Using
      linear regression analysis, we show a near 1:1 correlation between sample
      concentrations, with r(2) values between 0.98 and 0.99 and slopes between 0.97
      and 1.10. This method demonstrates that assays resulting in unusable standard
      curves do not require re-assay of all samples. Instead, the experimental sample
      concentrations can be retrieved saving the investigator the time and resources
      required to rerun samples or repeat entire experiments.

PMID- 22982521
TI  - [Polyneuropathies of pregnancy and the postpartum period in Burkina Faso].
AB  - Polyneuropathies of pregnancy and the postpartum period are considered rare but
      also understudied in Sub-Saharan Africa. They are usually related to a thiamine
      deficiency in under- or malnourished women. Our aim was to study the clinical and
      etiological factors of this disease in the Yalgado Ouedraogo University Hospital
      of Ouagadougou in Burkina Faso. Our prospective cross-sectional study lasted for
      20 months, from August 2008 to April 2010. During the period, 27 women received
      this diagnosis. Their mean age was 27.5 years (range: 20 to 38). All but two
      (92%) had no or a very small or a modest income. Their monotonous diet was based
      on local cereals and available irregularly. Almost all (24/27, 89%) had developed
      one or more diseases during pregnancy, primarily excessive vomiting (70%) and
      severe anorexia (89%). Sensory symptoms were present in 70% of cases, and
      sensorimotor symptoms in 30%. The cause was always a deficiency-related
      polyneuropathy. All patients were treated with vitamin B complex and all symptoms
      disappeared by the third month of treatment. We conclude that polyneuropathies
      during pregnancy and during the postpartum delivery occur in women eating an
      unbalanced diet and living in a deprived social and economic situation and that
      it is manifested by serious vomiting and anorexia.

PMID- 22982522
TI  - Comparative phosphoproteomics studies of macrophage response to bacterial
      virulence effectors.
AB  - Lipopolysaccharide (LPS) from Gram-negative bacteria and cell wall components
      from Gram-positive bacteria are pathogenic inducers of host cell innate immune
      systems. In this study, we adapted stable isotope labeling with amino acid in
      cell culture (SILAC) and Fe(3+)-IMAC phosphopeptide enrichment method to study
      phosphoproteomic changes in bacterial virulence factors induced macrophage RAW
      264.7 cells. In total, we quantified 2657 phosphopeptides and 1990
      phosphopeptides in LPS treated and heat-killed Staphylococcus aureus (HKSA)
      treated macrophage samples respectively. Functional bioinformatics analysis was
      followed to show differences between LPS and HKSA stimulated macrophage signaling
      pathways. We identified differences in immune-related signaling networks,
      including Erk1/2 signaling pathway, Jak/Stat signaling pathway, Jnk signaling
      pathway, and revealed differences in cytoskeleton reorganization, GTPase
      regulators and in phosphorylation motifs.

PMID- 22982523
TI  - Snake venomics across genus Lachesis. Ontogenetic changes in the venom
      composition of Lachesis stenophrys and comparative proteomics of the venoms of
      adult Lachesis melanocephala and Lachesis acrochorda.
AB  - We report the proteomic analysis of ontogenetic changes in venom composition of
      the Central American bushmaster, Lachesis stenophrys, and the characterization of
      the venom proteomes of two congeneric pitvipers, Lachesis melanocephala (black
      headed bushmaster) and Lachesis acrochorda (Chochoan bushmaster). Along with the
      previous characterization of the venom proteome of Lachesis muta muta (from
      Bolivia), our present outcome enables a comparative overview of the composition
      and distribution of the toxic proteins across genus Lachesis. Comparative
      venomics revealed the close kinship of Central American L. stenophrys and L.
      melanocephala and support the elevation of L. acrochorda to species status. Major
      ontogenetic changes in the toxin composition of L. stenophrys venom involves
      quantitative changes in the concentration of vasoactive peptides and serine
      proteinases, which steadily decrease from birth to adulthood, and age-dependent
      de novo biosynthesis of Gal-lectin and snake venom metalloproteinases (SVMPs).
      The net result is a shift from a bradykinin-potentiating and C-type natriuretic
      peptide (BPP/C-NP)-rich and serine proteinase-rich venom in newborns and 2-years
      old juveniles to a (PI>PIII) SVMP-rich venom in adults. Notwithstanding minor
      qualitative and quantitative differences, the venom arsenals of L. melanocephala
      and L. acrochorda are broadly similar between themselves and also closely mirror
      those of adult L. stenophrys and L. muta venoms. The high conservation of the
      overall composition of Central and South American bushmaster venoms provides the
      ground for rationalizing the "Lachesis syndrome", characterized by vagal
      syntomatology, sensorial disorders, hematologic, and cardiovascular
      manifestations, documented in envenomings by different species of this wide
      ranging genus. This finding let us predict that monospecific Lachesic antivenoms
      may exhibit paraspecificity against all congeneric species.

PMID- 22982524
TI  - Synthesis and evaluation of anticonvulsant and antidepressant activities of 5
      alkoxytetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives.
AB  - A series of 5-alkoxytetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives were
      synthesized and their anticonvulsant and antidepressant activities were
      evaluated. Pharmacological tests showed that four of the synthesized compounds
      had weak anticonvulsant activity, while most of the compounds had excellent
      antidepressant activity. The most active compound was 5-(2,4
      dichlorobenzyloxy)tetrazolo[1,5-c] thieno[2,3-e]pyrimidine, which decreased the
      immobility time by 51.62% at a dose of 100 mg/kg. The results of open-field tests
      of this compound indicated that it had no significant effects on the locomotor
      activity compared with the control group at the doses assayed in the forced
      swimming tests test. This means that the antidepressant activity detected in the
      FST for the compound is not the result of central nervous system stimulant
      properties, and further confirms its antidepressant-like effect.

PMID- 22982525
TI  - Synthesis and biological evaluation of selective and potent cyclin-dependent
      kinase inhibitors.
AB  - A new series of 2,6,9-trisubstituted purines, structurally related to the cyclin
      dependent kinase (CDK) inhibitor Roscovitine, has been synthesized. These
      compounds mainly differ by the substituent on the C-2 position which encompasses
      a diol group. These compounds were screened for kinase inhibitory activities and
      antiproliferative effects. They were shown to be potent inhibitors of cyclin
      dependent kinases but also, for some of them of casein kinase 1 (CK1) and dual
      specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). The inhibition
      of kinases was accompanied by an antiproliferative effect against several tumor
      cell-lines. The most potent derivatives inhibited SH-SY5Y (neuroblastoma) tumor
      cell line with an IC(50) < 0.5 MUM which means approximately a 30 fold increase
      compared to Roscovitine. A valine ester was also prepared from the most potent
      inhibitor to serve as a prodrug.

PMID- 22982526
TI  - Docking studies, synthesis, characterization of some novel oxazine substituted 9
      anilinoacridine derivatives and evaluation for their antioxidant and anticancer
      activities as topoisomerase II inhibitors.
AB  - A series of 9-anilinoacridines substituted with oxazine derivatives were
      synthesized to evaluate their antioxidant and anticancer activity against Daltons
      Lymphoma Ascites (DLA) cell growth by in vitro method. It was revealed that these
      conjugates exhibited significant antioxidant and anticancer activity (inhibition
      of DLA cell proliferation). Among these agents, compounds 5a, 5h, 5i, 5j were the
      most cytotoxic with CTC(50) value of 140-250 MUg/mL. The docking studies of the
      synthesized compounds were performed towards the key Topoisomerase II (1QZR) by
      using Schrodinger Maestro 9.2 version. The oxazine substituted 9-anilinoacridine
      derivatives 5a, 5h, 5i, 5j have significant anticancer activity as topoisomerase
      II inhibitors.

PMID- 22982527
TI  - Synthesis and biological activities of 4-substituted pyrrolo[2,3-a]carbazole Pim
      kinase inhibitors.
AB  - Pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in
      vitro antiproliferative activities. In the present study, we report the synthesis
      and biological activities (Pim kinase inhibition and in vitro antiproliferative
      potency) of new 4-substituted pyrrolo[2,3-a]carbazoles. The results demonstrated
      that the Pim kinase inhibitory potency (especially Pim-3) can be conserved for
      pyrrolo[2,3-a]carbazoles bearing a methoxycarbonyl group at the 4-position
      without a formyl at the 3-position. Moreover, compound 27 that was found to be
      active against Pim-1 and Pim-3 kinases showed antiproliferative activities in the
      micromolar range.

PMID- 22982529
TI  - Population structure and exotoxin gene content of methicillin-susceptible
      Staphylococcus aureus from Spanish healthy carriers.
AB  - The population structure of 111 methicillin-susceptible Staphylococcus aureus
      (MSSA), recovered in Spain from healthy and risk-free carriers was investigated
      using pulsed-field gel electrophoresis (PFGE), spa (staphylococcal protein A)
      typing, multi locus sequence typing (MLST) and the accessory gene regulator
      (agr). Results from the different techniques were highly concordant, and revealed
      twelve clonal complexes (CCs): CC30 (27%), CC5 (18.9%), CC45 (16.2%), CC15
      (11.7%), CC25 (8.1%), CC1, CC9 (3.6% each), CC59, CC97 and CC121 (2.7% each),
      CC72 (1.8%) and CC8 (0.9%). Isolates with genetic backgrounds of hospital
      acquired MSSA were detected and, consistent with the ability of diverse MSSA to
      act as recipients of the SCCmec cassette, a MSSA isolate from a healthy carrier
      shared the ST, spa-type and agr-type of a MRSA clone recovered in a hospital of
      the same region. All except two fragments of the PGFE-profiles of these isolates
      were identical, and the differential fragment of the MRSA carried mecA. Analyses
      of the exotoxin gene content of the nasal isolates revealed an increase in the
      number of exotoxin genes over time. This, together with the detection of lukPV
      and the high frequency of tst, exfoliatin and enterotoxin genes, is worrisome and
      requires further surveillance.

PMID- 22982528
TI  - Identifying human-rhesus macaque gene orthologs using heterospecific SNP probes.
AB  - We genotyped a Chinese and an Indian-origin rhesus macaque using the Affymetrix
      Genome-Wide Human SNP Array 6.0 and cataloged 85,473 uniquely mapping
      heterospecific SNPs. These SNPs were assigned to rhesus chromosomes according to
      their probe sequence alignments as displayed in the human and rhesus reference
      sequences. The conserved gene order (synteny) revealed by heterospecific SNP maps
      is in concordance with that of the published human and rhesus macaque genomes.
      Using these SNPs' original human rs numbers, we identified 12,328 genes annotated
      in humans that are associated with these SNPs, 3674 of which were found in at
      least one of the two rhesus macaques studied. Due to their density, the
      heterospecific SNPs allow fine-grained comparisons, including approximate
      boundaries of intra- and extra-chromosomal rearrangements involving gene
      orthologs, which can be used to distinguish rhesus macaque chromosomes from human
      chromosomes.

PMID- 22982530
TI  - Clinical evaluation of the incidence of prosthetic complications in implant
      crowns constructed with UCLA castable abutments. A cohort follow-up study.
AB  - OBJECTIVES: To evaluate the incidence of prosthetic complications in implant
      retained crowns made with UCLA castable abutments and to identify possible risk
      factors with a view to establishing recommendations to help predict the success
      of such restorations. METHODS: A cohort follow-up study was carried out in 71
      partially dentate patients rehabilitated with 93 implant-retained single crowns.
      Data regarding socio-demographic background, anatomical features, implant-, and
      prosthesis-related variables were recorded. The incidence rate (%), relative risk
      (RR) and odds ratio (OR) were applied for predictive risk factors. ANOVA and
      Student t-tests were used to compare quantitative variables, the chi-square test
      was used to compare proportions and also a logistic regression analysis was
      performed. The statistical significance was set at alpha = 0.05. RESULTS: Two
      implants (2.2%) were lost during the first year of function. The incidence of
      prosthetic complications in the observed mean period (26.2 +/- 15.4 months) was
      11.9%, consisting of screw loosening (10.8%) and ceramic fracture (1.1%). A
      higher tendency for prosthetic complications was noticed in posterior mandibular
      crowns restoring saddles longer than 10 mm with mesiodistal cantilevers longer
      than 6mm, having natural antagonists, after long-term use (>20 months), with
      initial torque values superior than 30 Ncm. CONCLUSIONS: Screw loosening is the
      most frequent complication in implant-retained crowns fabricated with UCLA
      abutments cast in cobalt-chromium. Nevertheless, the connection usually remains
      stable after retightening the screws. A high survival rate was recorded, and
      these prostheses may be a suitable treatment option. CLINICAL SIGNIFICANCE: Based
      on the study findings, the risk of prosthetic complications is expected to
      increase when long-span posterior edentulous areas are rehabilitated with single
      implant-supported crowns. The antagonist occlusal plane should be restored to
      prevent torsional forces and overloading. Implant systems with initial torque
      values less than 30 Ncm should be selected.

PMID- 22982531
TI  - Quinone- and nitroreductase reactions of Thermotoga maritima peroxiredoxin
      nitroreductase hybrid enzyme.
AB  - Thermotoga maritima peroxiredoxin-nitroreductase hybrid enzyme (Prx-NR) consists
      of a FMN-containing nitroreductase (NR) domain fused to a peroxiredoxin (Prx)
      domain. These domains seem to function independently as no electron transfer
      occurs between them. The reduction of quinones and nitroaromatics by NR proceeded
      in a two-electron manner, and follows a 'ping-pong' scheme with sometimes
      pronounced inhibition by quinone substrate. The comparison of steady- and
      presteady-state kinetic data shows that in most cases, the oxidative half
      reaction may be rate-limiting in the catalytic cycle of NR. The enzyme was
      inhibited by dicumarol, a classical inhibitor of oxygen-insensitive
      nitroreductases. The reduction of quinones and nitroaromatic compounds by Prx-NR
      was characterized by the linear dependence of their reactivity (logk(cat)/K(m))
      on their single-electron reduction potentials E(7)(1), while the reactivity of
      quinones markedly exceeded the one with nitroaromatics. It shows that NR lacks
      the specificity for the particular structure of these oxidants, except their
      single-electron accepting potency and the rate of electron self-exchange. It
      points to the possibility of a single-electron transfer step in a net two
      electron reduction of quinones and nitroaromatics by T. maritima Prx-NR, and to a
      significant diversity of the structures of flavoenzymes which may perform the two
      electron reduction of quinones and nitroaromatics.

PMID- 22982533
TI  - Significance of persistent cytogenetic abnormalities on myeloablative allogeneic
      stem cell transplantation in first complete remission.
AB  - Risk stratification is important to identify patients with acute myelogenous
      leukemia (AML) who might benefit from allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) in first complete remission. We retrospectively
      studied 150 patients with AML and diagnostic cytogenetic abnormalities who
      underwent myeloablative allo-HSCT while in first complete remission to evaluate
      the prognostic impact of persistent cytogenetic abnormalities at allo-HSCT. Three
      risk groups were identified. Patients with favorable/intermediate cytogenetics at
      diagnosis (n = 49) and patients with unfavorable cytogenetics at diagnosis but
      without a persistent abnormal clone at allo-HSCT (n = 83) had a similar 3-year
      leukemia-free survival of 58%-60% despite the higher 3-year relapse incidence
      (RI) in the latter group (32.3%, versus 16.8% in the former group). A third group
      of patients with unfavorable cytogenetics at diagnosis and a persistent abnormal
      clone at allo-HSCT (n = 15) had the worst prognosis, with a 3-year RI of 57.5%
      and 3-year leukemia-free survival of only 29.2%. These data suggest that patients
      with AML and unfavorable cytogenetics at diagnosis and a persistent abnormal
      clone at allo-HSCT are at high risk for relapse after allo-HSCT. These patients
      should be considered for clinical trials designed to optimize conditioning
      regimens and/or to use preemptive strategies in the posttransplantion setting
      aimed at decreasing RI.

PMID- 22982532
TI  - NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase
      family.
AB  - NADPH-cytochrome P450 oxidoreductase (CYPOR) and nitric oxide synthase (NOS), two
      members of the diflavin oxidoreductase family, are multi-domain enzymes
      containing distinct FAD and FMN domains connected by a flexible hinge. FAD
      accepts a hydride ion from NADPH, and reduced FAD donates electrons to FMN, which
      in turn transfers electrons to the heme center of cytochrome P450 or NOS
      oxygenase domain. Structural analysis of CYPOR, the prototype of this enzyme
      family, has revealed the exact nature of the domain arrangement and the role of
      residues involved in cofactor binding. Recent structural and biophysical studies
      of CYPOR have shown that the two flavin domains undergo large domain movements
      during catalysis. NOS isoforms contain additional regulatory elements within the
      reductase domain that control electron transfer through Ca(2+)-dependent
      calmodulin (CaM) binding. The recent crystal structure of an iNOS Ca(2+)/CaM-FMN
      construct, containing the FMN domain in complex with Ca(2+)/CaM, provided
      structural information on the linkage between the reductase and oxgenase domains
      of NOS, making it possible to model the holo iNOS structure. This review
      summarizes recent advances in our understanding of the dynamics of domain
      movements during CYPOR catalysis and the role of the NOS diflavin reductase
      domain in the regulation of NOS isozyme activities.

PMID- 22982534
TI  - T cell-depleted stem cell transplantation for adults with high-risk acute
      lymphoblastic leukemia: long-term survival for patients in first complete
      remission with a decreased risk of graft-versus-host disease.
AB  - Consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      provides a survival benefit to patients with acute lymphoblastic leukemia (ALL).
      We have previously reported comparable survival and relapse rates after T cell
      depleted (TCD) allo-HSCT compared with unmodified transplantations for acute
      myelogenous leukemia, myelodysplastic syndrome, and non-Hodgkin lymphoma with
      significantly decreased graft-versus-host disease (GVHD). We performed a 56
      patient retrospective study to evaluate TCD allo-HSCT for the treatment of ALL
      after myeloablative total body irradiation-based therapy. The 2-year and 5-year
      overall survival rates for patients with ALL after TCD allo-HSCT were 0.39 (95%
      confidence interval [CI], 0.26-0.52) and 0.32 (95% CI, 0.19-0.44), respectively,
      and the 2-year and 5-year disease-free survival rates were 0.38 (95% CI, 0.25
      0.50) and 0.32 (95% CI, 0.20-0.44). There was a trend toward improved survival of
      patients who underwent TCD allo-HSCT in first complete remission compared with
      those who did so in other remission states. The cumulative incidence of grade II
      IV acute GVHD at 1 year was 0.20 (95% CI, 0.10-0.31), and no patients developed
      grade IV acute GVHD. The cumulative incidence of chronic GVHD in 41 evaluable
      patients at 2 and 5 years was 0.15 (95% CI, 0.04-0.26), and that of extensive
      chronic GVHD at 2 and 5 years was 0.05 (95% CI, 0-11.6). We demonstrate OS and
      DFS rates that compare favorably to unmodified allo-HSCT with lower rates of
      GVHD.

PMID- 22982536
TI  - Prodigiosin activates endoplasmic reticulum stress cell death pathway in human
      breast carcinoma cell lines.
AB  - Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against
      diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated
      by accumulation of unfolded or misfolded proteins in the ER lumen and may induce
      cell death when irremediable. In this study, the role of ER stress in prodigiosin
      induced cytotoxicity was elucidated for the first time. Comparable to the ER
      stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers
      GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the
      unfolded protein response (UPR) in multiple human breast carcinoma cell lines,
      confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up
      regulated CHOP, as evidenced by its promoting effect on the CHOP promoter
      activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity
      to evoke PARP cleavage, reduce cell viability and suppress colony formation,
      highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress
      response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent
      manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced
      PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells,
      suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited
      cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant
      negative blockade of PERK-mediated eIF2alpha phosphorylation impaired prodigiosin
      induced CHOP up-regulation and PARP cleavage. Collectively, these results
      identified ER stress-mediated cell death as a mode-of-action of prodigiosin's
      tumoricidal effect. Mechanistically, prodigiosin engages the IRE1-JNK and PERK
      eIF2alpha branches of the UPR signaling to up-regulate CHOP, which in turn
      mediates BCL2 suppression to induce cell death.

PMID- 22982537
TI  - A novel mechanism of filaggrin induction and sunburn prevention by beta
      damascenone in Skh-1 mice.
AB  - Understanding how oral administration of aroma terpenes can prevent sunburn or
      skin cancer in mice could lead to more effective and safer ways of blocking sun
      damage to human skin. To establish sunburn preventive activity, female Skh-1 mice
      were given oral beta-damascenone followed by irradiation with UVR from
      fluorescent 'sunlamps'. The following endpoints were evaluated versus controls at
      various times between 1 and 12 days after the terpene: whole genome gene
      expression and in situ immunohistochemistry of PCNA, keratin 10, filaggrin and
      caspase 14, and sunburn was evaluated at 5 days. UVR-induced sunburn was
      prevented by a single oral beta-damascenone dose as low as 20 MUL (0.95 mg/g body
      weight). Microarray analysis showed sunburn prevention doses of beta-damascenone
      up-regulated several types of cornification genes, including keratins 1 and 10,
      filaggrin, caspase 14, loricrin, hornerin and 6 late cornified envelope genes.
      Immunohistochemical studies of PCNA labeling showed that beta-damascenone
      increased the proliferation rates of the following cell types: epidermal basal
      cells, follicular outer root sheath cells and sebaceous gland cells. Keratin 10
      was not affected by beta-damascenone in epidermis, and filaggrin and caspase 14
      were increased in enlarged sebaceous glands. The thickness of the cornified
      envelope plus sebum layer nearly doubled within 1 day after administration of the
      beta-damascenone and remained at or above double thickness for at least 12 days.
      beta-Damascenone protected against sunburn by activating a sebaceous gland-based
      pathway that fortified and thickened the cornified envelope plus sebum layer in a
      way that previously has been observed to occur only in keratinocytes.

PMID- 22982539
TI  - Inhibition of p53 transactivation functionally interacts with microtubule
      stabilization to suppress excitotoxicity-induced axon degeneration.
AB  - Axon degeneration is a hallmark of many neurological disorders, including
      Alzheimer's disease, motor neuron disease, and nerve trauma. Multiple factors
      trigger axon degeneration, and glutamate excitotoxicity is one of them. We have
      recently found that stabilization of microtubules and components of the dynein
      dynactin complex modulate the process of excitotoxicity-induced axon
      degeneration. However, the molecular mechanisms involving these microtubule-based
      functions remain poorly understood. Here, we used hippocampal cultures and find
      that inhibition of p53 transactivation and microtubule stabilization function
      cooperatively to suppress excitotoxicity-induced mitochondrial dysfunction.
      Inhibition of p53 association with mitochondria has no effect on excitotoxicity
      induced mitochondrial dysfunction, however, induces axon degeneration in normal
      condition. Association of p150Glued with mitochondria is significantly increased
      by simultaneously inhibiting p53 transactivation and microtubule stabilization
      under excitotoxic condition. Importantly, we find that inhibition of p53
      transactivation and microtubule stabilization function cooperatively to suppress
      excitotoxicity-induced axon degeneration. Overexpression of p150Glued does not
      improve the effect by inhibition of p53 transactivation on axon degeneration
      suggesting that p150Glued and p53 function in a linear pathway in the process of
      axon degeneration.

PMID- 22982538
TI  - Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK
      and z-IETD-FMK is independent of their caspase inhibition properties.
AB  - The caspase inhibitors, benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)
      fluoromethylketone (z-VAD-FMK) and benzyloxycarbonyl (Cbz)-Ile-Glu (OMe)-Thr-Asp
      (OMe)-FMK (z-IETD-FMK) at non-toxic doses were found to be immunosuppressive and
      inhibit human T cell proliferation induced by mitogens and IL-2 in vitro. Both
      caspase inhibitors were shown to block NF-kappaB in activated primary T cells,
      but have little inhibitory effect on the secretion of IL-2 and IFN-gamma during T
      cell activation. However, the expression of IL-2 receptor alpha-chain (CD25) in
      activated T cells was inhibited by both z-VAD-FMK and z-IETD-FMK, whereas the
      expression of the early activated T cell marker, CD69 was unaffected. During
      primary T cell activation via the antigen receptor, both caspase-8 and caspase-3
      were activated and processed to their respective subunits, but neither caspase
      inhibitors had any effect on the processing of these two caspases. In sharp
      contrast both caspase inhibitors readily blocked apoptosis and the activation of
      caspases during FasL-induced apoptosis in activated primary T cells and Jurkat T
      cells. Collectively, the results demonstrate that both z-VAD-FMK and z-IETD-FMK
      are immunosuppressive in vitro and inhibit T cell proliferation without blocking
      the processing of caspase-8 and caspase-3.

PMID- 22982540
TI  - HSP-1/2, a major protein of equine seminal plasma, exhibits chaperone-like
      activity.
AB  - The major bovine seminal plasma protein, PDC-109 exhibits chaperone-like activity
      (CLA) against a variety of target proteins. The present studies show that the
      homologous protein from equine seminal plasma, HSP-1/2 also exhibits CLA and
      inhibits the thermal aggregation of target proteins such as lactate
      dehydrogenase, and DTT-induced aggregation of insulin in a concentration
      dependent manner. Phosphorylcholine binding inhibited the CLA of HSP-1/2,
      suggesting that aggregation state of the protein is important for this activity.
      These results demonstrate that HSP-1/2 functions as a molecular chaperone in
      vitro, and suggest that it may protect other proteins of equine seminal plasma
      from unfolding/misfolding or aggregation. These results suggest that homologous
      proteins from the seminal plasma of other mammals also exhibit CLA, which will be
      physiologically relevant.

PMID- 22982541
TI  - Sterol analogues with diamide side chains interfere with the intracellular
      localization of viral glycoproteins.
AB  - The need to develop novel antiviral agents encouraged us to assess the antiviral
      activity of synthetic sterol analogues with a diamide side chains. Cytotoxicity
      and antiviral activity of a family of azasterol previously synthesized was
      evaluated against herpes simplex virus 1 (HSV-1) (KOS and B2006) and vesicular
      stomatitis virus (VSV). This family of compounds was extended by the synthesis of
      novel analogs using an Ugi multicomponent reaction and their ability to inhibit
      viral multiplication was also evaluated. The results show that some of the
      compounds tested exert an antiviral activity. Besides, the effect of the
      azasterols on the intracellular localization of viral glycoproteins was examined.
      Strikingly, alteration on the glycoprotein D (gD) of HSV-1 fluorescence pattern
      was observed with both the antiherpetic compounds and the inactive azasterols.

PMID- 22982542
TI  - Online chromatic and scale-space microvessel-tracing analysis for transmitted
      light optical images.
AB  - Limited contrast in transmitted light optical images from intravital microscopy
      is problematic for analysing tumour vascular morphology. Moreover, in some cases,
      changes in vasculature are visible to a human observer but are not easy to
      quantify. In this paper two online algorithms are presented: scale-space vessel
      tracing and chromatic decomposition for analysis of the vasculature of SW1222
      human colorectal carcinoma xenografts growing in dorsal skin-fold "window"
      chambers in mice. Transmitted light optical images of tumours were obtained from
      mice treated with the tumour vascular disrupting agent, combretastatin-A-4
      phosphate (CA4P), or saline. The tracing algorithm was validated against hand
      traced vessels with accurate results. The measurements extracted with the
      algorithms confirmed the known effects of CA4P on tumour vascular topology.
      Furthermore, changes in the chromaticity suggest a deoxygenation of the blood
      with a recovery to initial levels in CA4P-treated tumours relative to the
      controls. The algorithms can be freely applied to other studies through the
      CAIMAN website (CAncer IMage ANalysis: http://www.caiman.org.uk).

PMID- 22982535
TI  - The immune system and developmental programming of brain and behavior.
AB  - The brain, endocrine, and immune systems are inextricably linked. Immune
      molecules have a powerful impact on neuroendocrine function, including hormone
      behavior interactions, during health as well as sickness. Similarly, alterations
      in hormones, such as during stress, can powerfully impact immune function or
      reactivity. These functional shifts are evolved, adaptive responses that organize
      changes in behavior and mobilize immune resources, but can also lead to pathology
      or exacerbate disease if prolonged or exaggerated. The developing brain in
      particular is exquisitely sensitive to both endogenous and exogenous signals, and
      increasing evidence suggests the immune system has a critical role in brain
      development and associated behavioral outcomes for the life of the individual.
      Indeed, there are associations between many neuropsychiatric disorders and immune
      dysfunction, with a distinct etiology in neurodevelopment. The goal of this
      review is to describe the important role of the immune system during brain
      development, and to discuss some of the many ways in which immune activation
      during early brain development can affect the later-life outcomes of neural
      function, immune function, mood and cognition.

PMID- 22982543
TI  - Comparisons of different methods to train a young zebra finch (Taeniopygia
      guttata) to learn a song.
AB  - Like humans, oscine songbirds exhibit vocal learning. They learn their song by
      imitating conspecifics, mainly adults. Among them, the zebra finch (Taeniopygia
      guttata) has been widely used as a model species to study the behavioral,
      cellular and molecular substrates of vocal learning. Various methods using taped
      song playback have been used in the laboratory to train young male finches to
      learn a song. Since different protocols have been applied by different research
      groups, the efficiency of the studies cannot be directly compared. The purpose of
      our study was to address this problem. Young finches were raised by their mother
      alone from day post hatching (dph) 10 and singly isolated from dph 35. One week
      later, exposure to a song model began, either using a live tutor or taped
      playback (passive or self-elicited). At dph 100, the birds were transferred to a
      common aviary. We observed that one-to-one live tutoring is the best method to
      get a fairly complete imitation. Using self-elicited playback we observed high
      inter-individual variability; while some finches learned well (including good
      copying of the song model), others exhibited poor copying. Passive playback
      resulted in poor imitation of the model. We also observed that finches exhibited
      vocal changes after dph 100 and that the range of these changes was negatively
      related to their imitation of the song model. Taken together, these results
      suggest that social aspects are predominant in the success outcome of song
      learning in the zebra finch.

PMID- 22982545
TI  - Optimizing immuno-labeling for correlative fluorescence and electron microscopy
      on a single specimen.
AB  - Correlative fluorescence and electron microscopy has become an indispensible tool
      for research in cell biology. The integrated Laser and Electron Microscope (iLEM)
      combines a Fluorescence Microscope (FM) and a Transmission Electron Microscope
      (TEM) within one set-up. This unique imaging tool allows for rapid identification
      of a region of interest with the FM, and subsequent high resolution TEM imaging
      of this area. Sample preparation is one of the major challenges in correlative
      microscopy of a single specimen; it needs to be apt for both FM and TEM imaging.
      For iLEM, the performance of the fluorescent probe should not be impaired by the
      vacuum of the TEM. In this technical note, we have compared the fluorescence
      intensity of six fluorescent probes in a dry, oxygen free environment relative to
      their performance in water. We demonstrate that the intensity of some
      fluorophores is strongly influenced by its surroundings, which should be taken
      into account in the design of the experiment. Furthermore, a freeze-substitution
      and Lowicryl resin embedding protocol is described that yields excellent membrane
      contrast in the TEM but prevents quenching of the fluorescent immuno-labeling.
      The embedding protocol results in a single specimen preparation procedure that
      performs well in both FM and TEM. Such procedures are not only essential for the
      iLEM, but also of great value to other correlative microscopy approaches.

PMID- 22982544
TI  - Structural characterization and inhibition of the Plasmodium Atg8-Atg3
      interaction.
AB  - The autophagy-related proteins are thought to serve multiple functions in
      Plasmodium and are considered essential to parasite survival and development. We
      have studied two key interacting proteins, Atg8 and Atg3, of the autophagy
      pathway in Plasmodium falciparum. These proteins are vital for the formation and
      elongation of the autophagosome and essential to the process of macroautophagy.
      Autophagy may be required for conversion of the sporozoite into erythrocytic
      infective merozoites and may be crucial for other functions during asexual blood
      stages. Here we describe the identification of an Atg8 family interacting motif
      (AIM) in Plasmodium Atg3, which binds Plasmodium Atg8. We determined the co
      crystal structure of PfAtg8 with a short Atg3103-110 peptide, corresponding to
      this motif, to 2.2 A resolution. Our in vitro interaction studies are in
      agreement with our X-ray crystal structure. Furthermore they suggest an important
      role for a unique Apicomplexan loop absent from human Atg8 homologues. Prevention
      of the protein-protein interaction of full length PfAtg8 with PfAtg3 was achieved
      at low micromolar concentrations with a small molecule, 1,2,3-trihydroxybenzene.
      Together our structural and interaction studies represent a starting point for
      future antimalarial drug discovery and design for this novel protein-protein
      interaction.

PMID- 22982546
TI  - E1A expression might be controlled by miR-214 in cells with low adenovirus
      productivity.
AB  - In this study, we explored the differences in the human adenovirus type 5 (Ad5)
      production efficiencies of various cell types. The rate of virus production was
      higher in several cell lines, such as HeLa cells, than in Saos-2 cells. The
      expression level of the coxsackie and adenovirus receptor (CAR) protein, an
      adenovirus receptor, was very similar among these cell lines. Although no
      significant difference in the expression of early region 1A (E1A) mRNA was
      detected, the amount of E1A protein in the Saos-2 cells was markedly lower than
      that in HeLa cells. Proteasome inhibitor treatment did not rescue the quantity of
      E1A in the Saos-2 cells, suggesting that their decreased E1A protein expression
      is not due to protein decay. To examine the different expression of E1A protein,
      we employed a bioinformatics approach to identify miRNA that target the 3'
      untranslated region (3'-UTR) of E1A mRNA and identified miR-214 as a highly
      promising candidate. In Saos-2 cells, which have abundant levels of endogenous
      miR-214, the expression of luciferase was dramatically repressed, when the
      reporter gene was fused with the 3'-UTR of E1A mRNA including an miR-214 binding
      site. On the other hand, the activity from the same reporter was unchanged in
      HeLa cells, which display low-level miR-214 expression. Finally, we confirmed
      that the knockdown of the miR-214 upregulated the productive efficiency of the
      virus. These findings indicate that cellular miR-214 is capable of inhibiting
      adenovirus replication by regulating the translation of E1A protein.

PMID- 22982547
TI  - Total and differential white blood cell counts, high-sensitivity C-reactive
      protein, and the metabolic syndrome in non-affective psychoses.
AB  - The metabolic syndrome is highly prevalent in patients with schizophrenia, and is
      associated with a state of chronic, low-grade inflammation. Schizophrenia is also
      associated with increased inflammation, including aberrant blood levels of pro
      inflammatory cytokines and high-sensitivity C-reactive protein (hsCRP). The
      purpose of this study is to investigate the relationship between total and
      differential white blood cell (WBC) counts, hsCRP, and the metabolic syndrome in
      patients with schizophrenia and related non-affective psychoses. Fifty-nine
      inpatients and outpatients age 18-70 with non-affective psychotic disorders and
      22 controls participated in this cross-sectional study. Subjects had a fasting
      blood draw between 8 and 9 am for glucose, lipids, total and differential WBC
      counts, and hsCRP. Vital signs and anthropometric measures were obtained.
      Patients with non-affective psychosis and the metabolic syndrome had
      significantly higher total WBC counts, monocytes, and hsCRP levels than patients
      without the metabolic syndrome (p<=0.04 for each). In binary logistic regression
      analyses, after controlling for potential confounding effects of age, race, sex,
      age at first hospitalization for psychosis, parental history of diabetes,
      smoking, and psychotropic medications, total WBC count, monocytes, and hsCRP were
      significant predictors of metabolic syndrome in patients (p<=0.04 for each).
      hsCRP was also a significant predictor of increased waist circumference and
      triglycerides in patients (p<=0.05 for each). Our findings suggest that
      measurement of total and differential WBC counts and hsCRP blood levels may be
      germane to the clinical care of patients with schizophrenia and related
      disorders, and support an association between inflammation and metabolic
      disturbance in these patients.

PMID- 22982548
TI  - Gonadal abnormalities in frogs (Lithobates spp.) collected from managed wetlands
      in an agricultural region of Nebraska, USA.
AB  - Nebraska's Rainwater Basin (RWB) provides important wetland habitat for North
      American migratory birds. Concern exists that pesticide and nutrient runoff from
      surrounding row-crops enters wetlands degrading water quality and adversely
      affecting birds and wildlife. Frogs may be especially vulnerable. Plains leopard
      (Lithobates blairi) metamorphs from RWB wetlands with varying concentrations of
      pesticides were evaluated for a suite of biomarkers of exposure to endocrine
      active chemicals. Froglets had ovarian dysgenesis, high rates of testicular
      oocytes, and female-biased sex ratios however, there was no clear statistical
      association between pesticide concentrations and biomarkers. Data interpretation
      was hindered because timing and duration of exposures were unknown and due to an
      incomplete understanding of L. blairi sexual development. Emphasis is on
      describing the complex developmental biology of closely-related leopard frogs,
      how this understanding can explain RWB L. blairi anomalies, and the need for
      sampling at the appropriate life stage.

PMID- 22982549
TI  - Chemical stabilization of metals and arsenic in contaminated soils using oxides-
      a review.
AB  - Oxides and their precursors have been extensively studied, either singly or in
      combination with other amendments promoting sorption, for in situ stabilization
      of metals and As in contaminated soils. This remediation option aims at reducing
      the available fraction of metal(loid)s, notably in the root zone, and thus
      lowering the risks associated with their leaching, ecotoxicity, plant uptake and
      human exposure. This review summarizes literature data on mechanisms involved in
      the immobilization process and presents results from laboratory and field
      experiments, including the subsequent influence on higher plants and aided
      phytostabilization. Despite the partial successes in the field, recent knowledge
      highlights the importance of long-term and large-scale field studies evaluating
      the stability of the oxide-based amendments in the treated soils and their
      efficiency in the long-term.

PMID- 22982550
TI  - Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole exposure to the
      antioxidant system in Pseudokirchneriella subcapitata.
AB  - We tested antioxidant responses of the green microalga Pseudokirchneriella
      subcapitata exposed to different concentrations of the three antibiotics
      erythromycin (ETM), ciprofloxacin (CPF) and sulfamethoxazole (SMZ). Measurements
      included the level of lipid peroxidation, the total antioxidative capacity and
      three major antioxidant mechanisms: the ascorbate-glutathione cycle, the
      xanthophyll cycle and the enzyme activities of catalase (CAT), superoxide
      dismutase (SOD), guaiacol glutathione peroxidase (GPX) and glutathione-S
      transferase (GST). Three antibiotics significantly affect the antioxidant system
      of P. subcapitata, but in different ways the alga was more tolerant to CPF and
      SMZ exposures than to ETM exposure. ETM caused reductions in AsA and GSH
      biosynthesis, ascorbate-glutathione cycle, xanthophylls cycle and antioxidant
      enzyme activities. The toxicity of CPF seems to be mainly overcome via induction
      of the ascorbate-glutathione cycle and CAT, SOD and GPX activities, while the
      toxicity of SMZ on the photosynthetic apparatus is predominantly reduced by the
      xanthophyll cycle and GST activity.

PMID- 22982551
TI  - Bioaugmentation with a consortium of bacterial nitrophenol-degraders for
      remediation of soil contaminated with three nitrophenol isomers.
AB  - A consortium consisting of para-nitrophenol utilizer Pseudomonas sp. strain WBC
      3, meta-nitrophenol utilizer Cupriavidus necator JMP134 and ortho-nitrophenol
      utilizer Alcaligenes sp. strain NyZ215 was inoculated into soil contaminated with
      three nitrophenol isomers for bioaugmentation. Accelerated removal of all
      nitrophenols was achieved in inoculated soils compared to un-inoculated soils,
      with complete removal of nitrophenols in inoculated soils occurring between 2 and
      16 days. Real-time polymerase chain reaction (PCR) targeting nitrophenol
      degradation functional genes indicated that the three strains survived and were
      stable over the course of the incubation period. The abundance of total
      indigenous bacteria (measured by 16S rRNA gene real-time PCR) was slightly
      negatively impacted by the nitrophenol contamination. Denaturing gradient gel
      electrophoresis profiles of total and group-specific indigenous community
      suggested a dynamic change in species richness occurred during the
      bioaugmentation process. Furthermore, Pareto-Lorenz curves and Community
      organization parameters indicated that the bioaugmentation process had little
      impact on species evenness within the microbial community.

PMID- 22982552
TI  - Intra- and inter-basin mercury comparisons: Importance of basin scale and time
      weighted methylmercury estimates.
AB  - To assess inter-comparability of fluvial mercury (Hg) observations at
      substantially different scales, Hg concentrations, yields, and bivariate
      relations were evaluated at nested-basin locations in the Edisto River, South
      Carolina and Hudson River, New York. Differences between scales were observed for
      filtered methylmercury (FMeHg) in the Edisto (attributed to wetland coverage
      differences) but not in the Hudson. Total mercury (THg) concentrations and
      bivariate-relationships did not vary substantially with scale in either basin.
      Combining results of this and a previously published multi-basin study, fish Hg
      correlated strongly with sampled water FMeHg concentration (rho = 0.78; p =
      0.003) and annual FMeHg basin yield (rho = 0.66; p = 0.026). Improved correlation
      (rho = 0.88; p < 0.0001) was achieved with time-weighted mean annual FMeHg
      concentrations estimated from basin-specific LOADEST models and daily streamflow.
      Results suggest reasonable scalability and inter-comparability for different
      basin sizes if wetland area or related MeHg-source-area metrics are considered.

PMID- 22982553
TI  - Changes in Sb speciation with waterlogging of shooting range soils and impacts on
      plant uptake.
AB  - A pot experiment was conducted to investigate the solubility and redox species of
      antimony (Sb) in a relocated shooting range soil and its uptake by Lolium perenne
      L. and Holcus lanatus L. under different water regimes. After 1-week
      waterlogging, the total Sb concentration in soil solution decreased from ~110 MUg
      L(-1) to <20 MUg L(-1), and slowly increased over the following 4 weeks, with the
      dissolution of Fe and Mn (hydr)oxides. In this process, half of the Sb in soil
      solution was reduced to Sb(III), which greatly affected the plant uptake of Sb.
      Waterlogging increased shoot Sb concentrations of L. perenne by ~10 fold but
      decreased uptake in H. lanatus by 80%. Results indicate that Sb might primarily
      be taken up as Sb(III) by L. perenne and as Sb(V) by H. lanatus. Temporary
      waterlogging of soil may increase the risk of trace elements entering the food
      chain.

PMID- 22982554
TI  - Biomonitors of urban air pollution: Magnetic studies and SEM observations of
      corticolous foliose and microfoliose lichens and their suitability for magnetic
      monitoring.
AB  - This study explored the suitability of available lichen species as air pollution
      biomonitors and assessed their potential for magnetic monitoring in cities.
      Several lichens on tree bark were collected in urban and industrial sites from
      Tandil city, as well as control sites. The results showed that magnetite-like
      minerals were the main magnetic carriers in all sites and samples. However, the
      concentration varied between clean and polluted sites. In addition, magnetic
      grain size-distribution showed clear differences between sites. Observations by
      scanning electron microscopy showed different particles in a variety of shapes
      and grain sizes; moreover, the presence of iron oxides and several toxic elements
      was detected by energy dispersive spectroscopy analysis. Although eleven lichen
      species were identified that appeared suitable for use as air-pollution monitors,
      three of them, Parmotrema pilosum, Punctelia hipoleucites and Dirinaria picta,
      occurred more frequently in the area, thus constituting appropriate species for
      future monitoring in the study area.

PMID- 22982555
TI  - Measuring participation after stroke: a review of frequently used tools.
AB  - OBJECTIVE: To identify and critique the measures currently used to assess
      participation in clinical stroke studies. DATA SOURCES: Relevant articles
      published between January 2001 and April 2012 identified through Medline, CINAHL,
      and ProQuest Central databases. STUDY SELECTION: Published articles involving
      poststroke assessment of participation. Case studies, cohort studies, and
      randomized controlled trials were included. DATA EXTRACTION: The most frequently
      used measures were identified and the psychometric properties evaluated. Three
      raters independently evaluated each measure relative to the first and second
      coding levels of the International Classification of Functioning, Disability and
      Health (ICF) Activities and Participation domain categories. DATA SYNTHESIS:
      Thirty-six measures were identified. The Stroke Impact Scale (SIS), London
      Handicap Scale, Assessment of Life Habits (LIFE-H), Frenchay Activities Index,
      and Activity Card Sort (ACS) were used most frequently. No single measure met
      criteria across all psychometric indices, and not one covered all 9 of the ICF
      Activities and Participation domains. The SIS, LIFE-H, and ACS covered the widest
      range. The domains covered most frequently were Community, Social and Civic Life,
      Domestic Life, and Mobility. Learning and Applying Knowledge, General Tasks and
      Demands, and Communication were the domains less frequently covered. CONCLUSIONS:
      This review identified and evaluated the most frequently used participation
      measures in clinical stroke studies. The SIS, LIFE-H, and ACS covered the ICF
      Activities and Participation domain categories most comprehensively. However,
      none of the measures covered all the ICF Activities and Participation domain
      categories. The information provided in this systematic review can be used to
      guide the selection of participation measures to meet specific clinical and
      research purposes.

PMID- 22982556
TI  - Differential effects of osmotic and SSR149415 challenges in maternally separated
      and control rats: the role of vasopressin on spatial learning.
AB  - Maternal separation (MS) has been demonstrated to up-regulate the hypothalamic
      vasopressin (VP) system. Intracerebrally released VP has been demonstrated to
      affect several types of animal behaviour, such as active/passive avoidance,
      social recognition, and learning and memory. However, the role of VP in spatial
      learning remains unclear. In the present study, we investigated the effects of an
      osmotic challenge and a V1b receptor-specific (V1bR) antagonist, SSR149415, on
      spatial learning of maternally separated and animal facility reared (AFR) adult
      male Wistar rats. The osmotic challenge was applied by injecting a hypertonic
      saline solution, 1h before the Morris water maze test (MWM). V1bR antagonist
      SSR149415 (5mg/kg) was injected i.p. twice (1h and 30 min) previous to the MWM. A
      combined treatment with both osmotic challenge and the SSR149415 was applied to
      the third group whereas rats for basal condition were injected with isotonic
      saline. Under basal condition no differences between AFR and MS groups were
      observed. MS rats showed severe impairment during the MWM after the osmotic
      challenge, but not after the administration of SSR149415. For AFR rats, the
      opposite phenomenon was observed. The joint application of SSR149415 and osmotic
      challenge restored the spatial learning ability for both groups. The differential
      impairment produced by osmotic stress-induced up-regulation and SSR149415 induced
      V1bR blockage in MS and control rats suggested that VP involvement in spatial
      learning depends on the individual intrinsic ligand-receptor functional state.

PMID- 22982557
TI  - Physiological and proteomic responses to single and repeated hypoxia in juvenile
      Eurasian perch under domestication--clues to physiological acclimation and
      humoral immune modulations.
AB  - We evaluated the physiological and humoral immune responses of Eurasian perch
      submitted to 4-h hypoxia in either single or repeated way. Two generations (F1
      and F5) were tested to study the potential changes in these responses with
      domestication. In both generations, single and repeated hypoxia resulted in
      hyperglycemia and spleen somatic index reduction. Glucose elevation and lysozyme
      activity decreased following repeated hypoxia. Complement hemolytic activity was
      unchanged regardless of hypoxic stress or domestication level. A 2D-DIGE
      proteomic analysis showed that some C3 components were positively modulated by
      single hypoxia while C3 up- and down-regulations and over-expression of
      transferrin were observed following repeated hypoxia. Domestication was
      associated with a low divergence in stress and immune responses to hypoxia but
      was accompanied by various changes in the abundance of serum proteins related to
      innate/specific immunity and acute phase response. Thus, it appeared that the
      humoral immune system was modulated following single and repeated hypoxia
      (independently of generational level) or during domestication and that Eurasian
      perch may display physiological acclimation to frequent hypoxic disturbances.

PMID- 22982558
TI  - NMR as a tool to identify and characterize protein folding intermediates.
AB  - NMR spectroscopy is one of the few biophysical methods that can provide atomic
      level insight into the conformation of partially folded states and/or
      intermediates present along the protein folding pathway. Such studies are
      important not only within the context of the protein folding problem, but also to
      push forward the technique, due to the challenging nature of the systems studied.
      In fact, new NMR methods have been created, and applied, in an attempt to
      characterize the conformational features of the states along the folding pathway.
      Describing the structures along the folding landscape is of key importance to
      comprehend the folding reaction, design new proteins and to understand how
      several polypeptide chains are implicated in pathogenic amyloid states. The last
      advances in several approaches, which use NMR: (i) to monitor the protein folding
      pathway and/or, (ii) to characterize the structure of the intermediate states in
      such reaction are reviewed in this work.

PMID- 22982559
TI  - The invasion mode of GH(3) cells is conditioned by collagen subtype, and its
      efficiency depends on cell-cell adhesion.
AB  - The adaptation of GH(3) cells to different microenvironments is a consequence of
      a partial compromise with the tumor phenotype. A collagen type IV enriched
      microenvironment favors an invasive phenotype and increases the substrate
      adhesion capacity, whereas it decreases the phosphorylation of the regulatory
      myosin light chain and the aggregation capacity. In contrast, the higher internal
      tension and increased aggregation capacity induced by collagen type I/III are
      factors that reduce the invasion rate. Our results show, for the first time, the
      importance of collagen subtypes in determining the migratory strategy: collagen
      I/III favors mesenchymal-like motility, whereas collagen type IV induces an
      ameboid-type displacement. The reciprocal modulation of the myosin light chain
      kinase and the Rho-kinase determines the invasive capacity through changes in
      tissue cohesion, extracellular matrix affinity, regulatory myosin light chain
      phosphorylation and spatial distribution. The collagen subtype determines which
      of the mechano-transduction signaling pathways will regulate the tensional
      homeostasis and affect the invasion ability as well as the preferred migration
      strategy of the cells.

PMID- 22982560
TI  - Deposition of platinum on oxygen plasma treated carbon nanotubes by atomic layer
      deposition.
AB  - Platinum nanoparticles were deposited on oxygen plasma treated carbon nanotubes
      (CNTs) by atomic layer deposition (ALD). The treatment time with oxygen plasma
      generated by microwaves under a power of 600 W varied from 5 to 20 s. The number
      of ALD cycles was controlled at 5-125. X-ray photoelectron spectroscopic analysis
      indicated that oxygen plasma can graft oxygen-containing functional groups to the
      CNT surface to act as nucleation sites for growth of Pt nanoparticles. Formation
      of very uniform and well distributed Pt nanoparticles of a size of 1.60-4.80 nm
      was achieved. The growth rate of Pt nanoparticles could be controlled by the
      number of ALD cycles and oxygen plasma treatment time. This offers a dry process
      to deposit well-dispersed metallic nanoparticles on selected support materials.

PMID- 22982561
TI  - Insulin reduces LPS-induced lethality and lung injury in rats.
AB  - Insulin is a main glucose homeostatic hormone in the body. Previous reports
      showed that insulin also exerted anti-inflammatory actions and attenuated
      systemic inflammatory response. Here, we observed the effects and the underlying
      mechanisms of insulin on lipopolysaccharide (LPS)-induced acute lung injury
      (ALI). As revealed by survival study, insulin reduced mortality of rats and
      prolonged their survival time. Meanwhile, insulin significantly reduced the
      levels of inflammatory cytokines including tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and high mobility
      group box 1 (HMGB1) in bronchoalveolar lavage fluid (BALF). Besides, insulin
      markedly inhibited the expression of toll-like receptor 2 (TLR2), toll-like
      receptor 4 (TLR4) and nuclear factor-kappaB (NF-kappaB). Taken together, these
      data provided information that insulin attenuated LPS-induced ALI may attribute
      partly to the inhibition of the production of cytokines, and the expression of
      TLR2, TLR4 and NF-kappaB.

PMID- 22982562
TI  - Association of airway pentosidine levels with bronchodilator response mediated by
      salbutamol administration in asthmatic patients.
AB  - BACKGROUND: Recently, increased levels of pentosidine, an intermolecular cross
      linking type of advanced glycation end products, are observed in the airways of
      asthmatic patients. This study was designed to determine whether differences in
      bronchodilator response among individuals with asthma are attributable to
      pentosidine levels in their airways. METHODS: Fifty-six asthmatic patients (21
      with airway obstruction, 35 without airway obstruction) and 10 normal controls
      were included in this study. For asthmatic patients, we evaluated the spontaneous
      reversibility of airway obstruction or the reversibility that can be obtained
      after methacholine provocation. And we also measured pentosidine levels and
      percentage of sputum eosinophils in induced sputum, and exhaled nitric oxide (NO)
      levels. RESULTS: The pentosidine levels did not significantly differ between the
      two asthmatic subgroups with and without airway obstruction. In asthmatic
      patients without airway obstruction, airway hyperresponsiveness to methacholine
      (PC20 methacholine) was significantly correlated with sputum eosinophils and
      exhaled NO levels. In contrast, PC20 methacholine was not significantly
      correlated with pentosidine levels. In asthmatic patients with or without airway
      obstruction, bronchodilator response was not significantly correlated with sputum
      eosinophils and exhaled NO levels. However, bronchodilator response was closely
      correlated with pentosidine levels (asthmatics without airway obstruction: r = 
      0.54, p = 0.002; asthmatics with airway obstruction: r = -0.48, p = 0.03).
      CONCLUSIONS: Our results showed that pentosidine might be a potential biomarker
      reflecting the reduced bronchodilator response in asthma. This study will provide
      new insights into the mechanisms underlying persistent airway obstruction.

PMID- 22982563
TI  - Hydrogenation of ecdysteroids.
AB  - Catalytic hydrogenation is extensively used in steroid chemistry. The interest in
      transformations to the steroid skeleton of ecdysteroids has been increasing in
      the past years. Essential interest in the chemistry of ecdysteroids is caused by
      the selective reduction of Delta7 bond with the formation of 7,8-dihydro
      analogues, because this process allows one to obtain modified structures with new
      biological activity. Catalytic hydrogenation of isolated and conjugated double
      bonds and functional groups in ecdysteroids derivatives has been considered in
      review.

PMID- 22982565
TI  - Potent vasodilation effect of amurensin G is mediated through the phosphorylation
      of endothelial nitric oxide synthase.
AB  - Endothelial nitric oxide synthase (eNOS) has important regulatory functions in
      vascular tone, and impaired endothelium-dependent vasodilatation is a key event
      in diabetes and atherosclerosis. Vitis amurensis grapes containing resveratrol
      oligomers are consumed as wine and fruit and have antioxidative and
      neuroprotective effects. In this study, our goal was identify the most potent
      eNOS-activating compound among six stilbenes and oligostilbenes found in V.
      amurensis and to clarify its molecular mechanism. Among the six tested compounds,
      amurensin G most potently relaxed endothelium-intact aortic rings and increased
      eNOS phosphorylation and nitric oxide (NO) production. Amurensin G increased both
      estrogen receptor (ER) phosphorylation and ER-dependent gene transcription, and
      ERalpha or ERbeta inhibition suppressed amurensin G-mediated eNOS
      phosphorylation. Amurensin G enhanced the activities of phosphatidylinositol 3
      kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G
      stimulated eNOS phosphorylation. Moreover, amurensin G activated AMP-activated
      protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K
      activation were reversed by AMPK inhibition. ER inhibition reversed AMPK
      dependent PI3K activation in response to amurensin G. Amurensin G-mediated
      endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or
      PI3K. These results suggest that amurensin G enhances NO production via eNOS
      phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are
      required. Amurensin G would be applicable to prevent atherosclerosis.

PMID- 22982564
TI  - The cytochrome b5 dependent C-5(6) sterol desaturase DES5A from the endoplasmic
      reticulum of Tetrahymena thermophila complements ergosterol biosynthesis mutants
      in Saccharomyces cerevisiae.
AB  - Tetrahymena thermophila is a free-living ciliate with no exogenous sterol
      requirement. However, it can perform several modifications on externally added
      sterols including desaturation at C5(6), C7(8), and C22(23). Sterol desaturases
      in Tetrahymena are microsomal enzymes that require Cyt b(5), Cyt b(5) reductase,
      oxygen, and reduced NAD(P)H for their activity, and some of the genes encoding
      these functions have recently been identified. The DES5A gene encodes a C-5(6)
      sterol desaturase, as shown by gene knockout in Tetrahymena. To confirm and
      extend that result, and to develop new approaches to gene characterization in
      Tetrahymena, we have now, expressed DES5A in Saccharomyces cerevisiae. The DES5A
      gene was codon optimized and expressed in a yeast mutant, erg3Delta, which is
      disrupted for the gene encoding the S. cerevisiae C-5(6) sterol desaturase ERG3.
      The complemented strain was able to accumulate 74% of the wild type level of
      ergosterol, and also lost the hypersensitivity to cycloheximide associated with
      the lack of ERG3 function. C-5(6) sterol desaturases are expected to function at
      the endoplasmic reticulum. Consistent with this, a GFP-tagged copy of Des5Ap was
      localized to the endoplasmic reticulum in both Tetrahymena and yeast. This work
      shows for the first time that both function and localization are conserved for a
      microsomal enzyme between ciliates and fungi, notwithstanding the enormous
      evolutionary distance between these lineages. The results suggest that
      heterologous expression of ciliate genes in S. cerevisiae provides a useful tool
      for the characterization of genes in Tetrahymena, including genes encoding
      membrane protein complexes.

PMID- 22982566
TI  - Hypoxia, Mn-SOD and H(2)O(2) regulate p53 reactivation and PRIMA-1 toxicity
      irrespective of p53 status in human breast cancer cells.
AB  - Hypoxia is part of the tumor microenvironment favoring cancer resistance to
      chemotherapy mediated by mutations in the tumor suppressor p53 gene (TP53), or by
      conformational wt TP53 dysfunction. Since it is important to suppress tumor
      adaptation to hypoxia, irrespective of p53 status, we compared the efficacy of
      nutlin-3 which prevents MDM2-wt p53 interactions and PRIMA-1 which promotes
      mutant p53 reactivation and induction of massive apoptosis, under normoxia and
      hypoxia, against (a) SKBR3 breast carcinoma harboring a mutant p53R175H and over
      expressing erbB2; and (b) genetically matched breast cancer ERalpha positive MCF
      7 cells harboring either wt p53 or mutant p53 R175H. Under normoxia, PRIMA-1 was
      active against breast cancer cells harboring mutant p53. However, hypoxia further
      increased the susceptibility of mutant p53 breast cancer SKBR3 cells to lower
      PRIMA-1 levels, possibly through oxidative stress since this was counteracted by
      N-acetylcysteine. When using MCF-7 cells over-expressing mutant p53, PRIMA-1
      synergized with exogenous peroxidase to increase apoptosis concomitantly with
      induction of PUMA and Mn-SOD, under normoxia. Wt p53 MCF-7 cells responded to
      hypoxia by increasing superoxide dismutase and their reactivity with the PAb240
      antibody, known to recognize conformationally-inactive p53. This correlated with
      sensitization of wt p53 MCF-7 cells to PRIMA-1 but not to nutlin-3. PRIMA-1
      toxicity against normoxic wt p53 MCF-7 cells was also decreased by Mn-SOD over
      expression or when added with the glutathione antagonist, buthionine sulfoximine.
      This report shows for the first time that hypoxia increases PRIMA-1 toxicity in
      human breast cancer cells, partly by modulating p53 conformation and by inducing
      superoxide turnover. Our results suggest that PRIMA-1 may help to prevent hypoxia
      mediated tumor chemoresistance.

PMID- 22982567
TI  - Cytosolic lipid inclusions formed during infection by viral and bacterial
      pathogens.
AB  - Lipid inclusions play an important role in several pathological processes.
      Intracellular bacterial pathogens, such as members of the Mycobacterium and
      Chlamydia species are able to trigger the formation of lipid-laden foamy
      macrophages. Lipid droplet accumulation in the host constitutes a reservoir used
      by the bacilli for long-term persistence. Viruses need lipid droplets as assembly
      platform. We present the current knowledge about structural, functional and
      regulatory aspects of lipid inclusions.

PMID- 22982568
TI  - Thalamic glutamatergic afferents into the rat basolateral amygdala exhibit
      increased presynaptic glutamate function following withdrawal from chronic
      intermittent ethanol.
AB  - Amygdala glutamatergic neurotransmission regulates withdrawal induced anxiety
      like behaviors following chronic ethanol exposure. The lateral/basolateral
      amygdala receives multiple glutamatergic projections that contribute to overall
      amygdala function. Our lab has previously shown that rat cortical (external
      capsule) afferents express postsynaptic alterations during chronic intermittent
      ethanol exposure and withdrawal. However, thalamic (internal capsule) afferents
      also provide crucial glutamatergic input during behavioral conditioning, and they
      have not been studied in the context of chronic drug exposure. We report here
      that these thalamic inputs express altered presynaptic function during withdrawal
      from chronic ethanol exposure. This is characterized by enhanced release
      probability, as exemplified by altered paired-pulse ratios and decreased failure
      rates of unitary events, and increased concentrations of synaptic glutamate.
      Quantal analysis further implicates a withdrawal-dependent enhancement of the
      readily releasable pool of vesicles as a probable mechanism. These functional
      alterations are accompanied by increased expression of vesicle associated protein
      markers. These data demonstrate that chronic ethanol modulation of glutamate
      neurotransmission in the rat lateral/basolateral amygdala is afferent-specific.
      Further, presynaptic regulation of lateral/basolateral amygdala thalamic inputs
      by chronic ethanol may be a novel neurobiological mechanism contributing to the
      increased anxiety-like behaviors that characterize withdrawal.

PMID- 22982569
TI  - Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged
      leptin action in either region cross-desensitizes.
AB  - High-fat feeding or CNS leptin overexpression in chow-fed rats results in a
      region-specific cellular leptin resistance in medial basal hypothalamic regions
      and the ventral tegmental area (VTA). The present investigation examined the
      effects of targeted chronic leptin overexpression in the VTA as compared with the
      medial basal hypothalamus on long-term body weight homeostasis. The study also
      examined if this targeted intervention conserves regional leptin sensitivity or
      results in localized leptin resistance. Cellular leptin resistance was assessed
      by leptin-stimulated phosphorylation of signal transducers and activators of
      transcription 3 (STAT3). Tyrosine hydroxylase was measured in hypothalamus and
      VTA along with brown adipose tissue uncoupling protein 1. Leptin overexpression
      in VTA tempered HF-induced obesity, but to a slightly lesser extent than that
      with leptin overexpression in the hypothalamus. Moreover, the overexpression of
      leptin in the VTA stimulated cellular STAT3 phosphorylation in several regions of
      the medial basal hypothalamus, whereas verexpression in the hypothalamus did not
      activate STAT3 signaling in the VTA. This unidirectional trans-stimulation did
      not appear to involve migration of either the vector or the gene product. Long
      term leptin overexpression in either the medial basal hypothalamus or VTA caused
      desensitization of leptin signaling in the treated region and cross
      desensitization of leptin signaling in the untreated region. These results
      demonstrate a role of leptin receptors in the VTA in long-term body weight
      regulation, but the trans-activation of the hypothalamus following VTA leptin
      stimulation suggests that an integrative response involving both brain regions
      may account for the observed physiological outcomes.

PMID- 22982570
TI  - A panel of biological tests reveals developmental effects of pharmaceutical
      pollutants on late stage zebrafish embryos.
AB  - Standard toxicological assays using the zebrafish model system evaluate lethality
      and teratogenicity upon exposure during the first 2 days after fertilization. We
      tested the biological effects of several widely used drugs on zebrafish by acute
      treatment for 24 h starting at late embryonic stages, between 48 and 72 h post
      fertilization. For 4 out of 6 compounds, we observed a higher sensitivity of late
      stage zebrafish embryos for general toxicity (lethality) compared to younger
      embryos. Morphological defects such as edema, body curvature, delayed growth,
      decreased heart rate and locomotion were observed for each of the compounds
      tested, often at sublethal concentrations. Gene expression studies on a set of
      four selected genes revealed a specific regulatory pattern for the different
      compounds tested. Our results allow us to compare various toxicological endpoints
      and may contribute to the design of a rational high throughput approach using the
      zebrafish model.

PMID- 22982571
TI  - Expression in Pichia pastoris and characterization of echistatin, an RGD
      containing short disintegrin.
AB  - Echistatin (Ech) is a potent inhibitor of integrins and was isolated from snake
      Echis carinatus. To facilitate the study on the molecular determinants of
      integrin-ligand interactions, we expressed recombinant Ech and its mutants in the
      Pichia pastoris (P. pastoris) expression system and purified them to homogeneity
      with the yields of 2-7 mg/L. Ech produced in P. pastoris inhibited platelet
      aggregation with the IC(50) value of 210.5 nM. The sequential assignment and
      structure analysis of recombinant Ech were obtained by 2D and 3D (15)N-edited NMR
      spectra. These data suggests that Ech produced in P. pastoris retained its
      function and native fold. The results presented here provide the evidences that
      four disulfide-bonded peptide inhibitor of integrin, Ech, can be expressed in P.
      pastoris with correct fold and high yield. Platelet aggregation analysis of Ech
      mutants showed that the length of C-terminus and the K45 residue of Ech are
      important for interacting with integrin alphaIIbbeta3. We also found that
      recombinant Ech can inhibit the migration of human A375 melanoma cell. These
      findings may serve as the basis for understanding the activities of Ech.

PMID- 22982572
TI  - NetworkView: 3D display and analysis of protein.RNA interaction networks.
AB  - SUMMARY: NetworkView is an application for the display and analysis of
      protein.RNA interaction networks derived from structure and/or dynamics. These
      networks typically model individual protein residues and nucleic acid monomers as
      nodes and their pairwise contacts as edges with associated weights. NetworkView
      projects the network onto the underlying 3D molecular structure so that
      visualization and analysis of the network can be coupled to physical and
      biological properties. NetworkView is implemented as a plugin to the molecular
      visualization software VMD. AVAILABILITY AND IMPLEMENTATION: NetworkView is
      included with VMD, which is available at http://www.ks.uiuc.edu/Research/vmd/.
      Documentation, tutorials and supporting programs are available at
      http://www.scs.illinois.edu/schulten/software/. CONTACT:
      networkview@scs.illinois.edu

PMID- 22982573
TI  - DLRS: gene tree evolution in light of a species tree.
AB  - SUMMARY: PrIME-DLRS (or colloquially: 'Delirious') is a phylogenetic software
      tool to simultaneously infer and reconcile a gene tree given a species tree. It
      accounts for duplication and loss events, a relaxed molecular clock and is
      intended for the study of homologous gene families, for example in a comparative
      genomics setting involving multiple species. PrIME-DLRS uses a Bayesian MCMC
      framework, where the input is a known species tree with divergence times and a
      multiple sequence alignment, and the output is a posterior distribution over gene
      trees and model parameters. AVAILABILITY AND IMPLEMENTATION: PrIME-DLRS is
      available for Java SE 6+ under the New BSD License, and JAR files and source code
      can be downloaded from http://code.google.com/p/jprime/. There is also a slightly
      older C++ version available as a binary package for Ubuntu, with download
      instructions at http://prime.sbc.su.se. The C++ source code is available upon
      request. CONTACT: joel.sjostrand@scilifelab.se or jens.lagergren@scilifelab.se.
      SUPPLEMENTARY INFORMATION: PrIME-DLRS is based on a sound probabilistic model
      (Akerborg et al., 2009) and has been thoroughly validated on synthetic and
      biological datasets (Supplementary Material online).

PMID- 22982574
TI  - Efficient methods for identifying mutated driver pathways in cancer.
AB  - MOTIVATION: The first step for clinical diagnostics, prognostics and targeted
      therapeutics of cancer is to comprehensively understand its molecular mechanisms.
      Large-scale cancer genomics projects are providing a large volume of data about
      genomic, epigenomic and gene expression aberrations in multiple cancer types. One
      of the remaining challenges is to identify driver mutations, driver genes and
      driver pathways promoting cancer proliferation and filter out the unfunctional
      and passenger ones. RESULTS: In this study, we propose two methods to solve the
      so-called maximum weight submatrix problem, which is designed to de novo identify
      mutated driver pathways from mutation data in cancer. The first one is an exact
      method that can be helpful for assessing other approximate or/and heuristic
      algorithms. The second one is a stochastic and flexible method that can be
      employed to incorporate other types of information to improve the first method.
      Particularly, we propose an integrative model to combine mutation and expression
      data. We first apply our methods onto simulated data to show their efficiency. We
      further apply the proposed methods onto several real biological datasets, such as
      the mutation profiles of 74 head and neck squamous cell carcinomas samples, 90
      glioblastoma tumor samples and 313 ovarian carcinoma samples. The gene expression
      profiles were also considered for the later two data. The results show that our
      integrative model can identify more biologically relevant gene sets. We have
      implemented all these methods and made a package called mutated driver pathway
      finder, which can be easily used for other researchers. AVAILABILITY: A MATLAB
      package of MDPFinder is available at http://zhangroup.aporc.org/ShiHuaZhang.
      CONTACT: zsh@amss.ac.cn. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 22982575
TI  - Hereditary conjugated hyperbilirubinaemia: 37 years later.
AB  - Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted
      by the liver into bile. Failure of this system can lead to a buildup of
      conjugated bilirubin in the blood, resulting in jaundice. The mechanistic basis
      of bilirubin excretion and hyperbilirubinemia syndromes is largely understood,
      but that of Rotor syndrome, an autosomal recessive disorder characterized by
      conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake
      of anionic diagnostics, has remained enigmatic. Here, we analyzed 8 Rotor
      syndrome families and found that Rotor syndrome was linked to mutations predicted
      to cause complete and simultaneous deficiencies of the organic anion transporting
      polypeptides OATP1B1 and OATP1B3. These important detoxification-limiting
      proteins mediate uptake and clearance of countless drugs and drug conjugates
      across the sinusoidal hepatocyte membrane. OATP1B1 polymorphisms have previously
      been linked to drug hypersensitivities. Using mice deficient in Oatp1a/1b and in
      the multispecific sinusoidal export pump Abcc3, we found that Abcc3 secretes
      bilirubin conjugates into the blood, while Oatp1a/1b transporters mediate their
      hepatic re uptake. Transgenic expression of human OATP1B1 or OATP1B3 restored the
      function of this detoxification-enhancing liver-blood shuttle in Oatp1a/1b
      deficient mice. Within liver lobules, this shuttle may allow flexible transfer of
      bilirubin conjugates (and probably also drug conjugates) formed in upstream
      hepatocytes to downstream hepatocytes, thereby preventing local saturation of
      further detoxification processes and hepatocyte toxic injury. Thus, disruption of
      hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3
      deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3
      null mutations may confer substantial drug toxicity risks.

PMID- 22982576
TI  - Vascular peroxidase 1 catalyzes the formation of hypohalous acids:
      characterization of its substrate specificity and enzymatic properties.
AB  - The heme-containing peroxidase family comprises eight members in humans. The
      physiological and pathophysiological roles of heme-containing peroxidases are not
      well understood. Phagocyte-derived myeloperoxidase (MPO) utilizes chloride and
      bromide, in the presence of hydrogen peroxide (H(2)O(2)), to generate
      hypochlorous acid and hypobromous acid, potent oxidizing species that are known
      to kill invading pathogens. Vascular peroxidase 1 (VPO1) is a new member of the
      heme-containing peroxidase family; VPO1 is highly expressed in the cardiovascular
      system, lung, liver, pancreas, and spleen. However, functional roles of VPO1 have
      not been defined. In this report, we demonstrate the capacity for VPO1 to
      catalyze the formation of hypohalous acids, and characterize its enzymatic
      properties. VPO1, like MPO but unlike lactoperoxidase, is able to generate
      hypochlorous acid, hypobromous acid, and hypothiocyanous acid in the presence of
      H(2)O(2). Under physiological pH and concentrations of halides (100MUM KBr,
      100MUM KSCN, and 100mM NaCl), VPO1 utilizes approximately 45% of H(2)O(2) for the
      generation of hypobromous acid, 35% for hypothiocyanous acid, and 18% for
      hypochlorous acid. The specific activity of VPO1 is ~10- to 70-fold lower than
      that of MPO, depending on the specific substrate. These studies demonstrate that
      the enzymatic properties and substrate specificity of VPO1 are similar to MPO;
      however, significantly lower catalytic rate constants of VPO1 relative to MPO
      suggest the possibility of other physiologic roles for this novel heme-containing
      peroxidase.

PMID- 22982577
TI  - A decision rule for quantitative trait locus detection under the extended
      Bayesian LASSO model.
AB  - Bayesian shrinkage analysis is arguably the state-of-the-art technique for large
      scale multiple quantitative trait locus (QTL) mapping. However, when the
      shrinkage model does not involve indicator variables for marker inclusion, QTL
      detection remains heavily dependent on significance thresholds derived from
      phenotype permutation under the null hypothesis of no phenotype-to-genotype
      association. This approach is computationally intensive and more importantly, the
      hypothetical data generation at the heart of the permutation-based method
      violates the Bayesian philosophy. Here we propose a fully Bayesian decision rule
      for QTL detection under the recently introduced extended Bayesian LASSO for QTL
      mapping. Our new decision rule is free of any hypothetical data generation and
      relies on the well-established Bayes factors for evaluating the evidence for QTL
      presence at any locus. Simulation results demonstrate the remarkable performance
      of our decision rule. An application to real-world data is considered as well.

PMID- 22982578
TI  - Gene functional trade-offs and the evolution of pleiotropy.
AB  - Pleiotropy is the property of genes affecting multiple functions or characters of
      an organism. Genes vary widely in their degree of pleiotropy, but this variation
      is often considered a by-product of their evolutionary history. We present a
      functional theory of how pleiotropy may itself evolve. We consider genes that
      contribute to two functions, where contributing more to one function detracts
      from allocation to the second function. We show that whether genes become
      pleiotropic or specialize on a single function depends on the nature of trade
      offs as gene activities contribute to different traits and on how the
      functionality of these traits affects fitness. In general, when a gene product
      can perform well at two functions, it evolves to do so, but not when pleiotropy
      would greatly disrupt each function. Consequently, reduced pleiotropy should
      often evolve, with genes specializing on the trait that is currently more
      important to fitness. Even when pleiotropy does evolve, not all genes are
      expected to become equally pleiotropic; genes with higher levels of expression
      are more likely to evolve greater pleiotropy. For the case of gene duplicates, we
      find that perfect subfunctionalization evolves only under stringent conditions.
      More often, duplicates are expected to maintain a certain degree of functional
      redundancy, with the gene contributing more to trait functionality evolving the
      highest degree of pleiotropy. Gene product interactions can facilitate
      subfunctionalization, but whether they do so depends on the curvature of the
      fitness surface. Finally, we find that stochastic gene expression favors
      pleiotropy by selecting for robustness in fitness components.

PMID- 22982579
TI  - Epigenetic regulation of axonal growth of Drosophila pacemaker cells by histone
      acetyltransferase tip60 controls sleep.
AB  - Tip60 is a histone acetyltransferase (HAT) enzyme that epigenetically regulates
      genes enriched for neuronal functions through interaction with the amyloid
      precursor protein (APP) intracellular domain. However, whether Tip60-mediated
      epigenetic dysregulation affects specific neuronal processes in vivo and
      contributes to neurodegeneration remains unclear. Here, we show that Tip60 HAT
      activity mediates axonal growth of the Drosophila pacemaker cells, termed "small
      ventrolateral neurons" (sLNvs), and their production of the neuropeptide pigment
      dispersing factor (PDF) that functions to stabilize Drosophila sleep-wake cycles.
      Using genetic approaches, we show that loss of Tip60 HAT activity in the presence
      of the Alzheimer's disease-associated APP affects PDF expression and causes
      retraction of the sLNv synaptic arbor required for presynaptic release of PDF.
      Functional consequence of these effects is evidenced by disruption of the sleep
      wake cycle in these flies. Notably, overexpression of Tip60 in conjunction with
      APP rescues these sleep-wake disturbances by inducing overelaboration of the sLNv
      synaptic terminals and increasing PDF levels, supporting a neuroprotective role
      for dTip60 in sLNv growth and function under APP-induced neurodegenerative
      conditions. Our findings reveal a novel mechanism for Tip60 mediated sleep-wake
      regulation via control of axonal growth and PDF levels within the sLNv
      encompassing neural network and provide insight into epigenetic-based regulation
      of sleep disturbances observed in neurodegenerative diseases like Alzheimer's
      disease.

PMID- 22982580
TI  - Effectiveness of multidimensional cancer survivor rehabilitation and cost
      effectiveness of cancer rehabilitation in general: a systematic review.
AB  - INTRODUCTION: Many cancer survivors suffer from a combination of disease- and
      treatment-related morbidities and complaints after primary treatment. There is a
      growing evidence base for the effectiveness of monodimensional rehabilitation
      interventions; in practice, however, patients often participate in
      multidimensional programs. This study systematically reviews evidence regarding
      effectiveness of multidimensional rehabilitation programs for cancer survivors
      and cost-effectiveness of cancer rehabilitation in general. METHODS: The
      published literature was systematically reviewed. Data were extracted using
      standardized forms and were summarized narratively. RESULTS: Sixteen
      effectiveness and six cost-effectiveness studies were included. Multidimensional
      rehabilitation programs were found to be effective, but not more effective than
      monodimensional interventions, and not on all outcome measures. Effect sizes for
      quality of life were in the range of -0.12 (95% confidence interval [CI], -0.45
      0.20) to 0.98 (95% CI, 0.69-1.29). Incremental cost-effectiveness ratios ranged
      from -?16,976, indicating cost savings, to ?11,057 per quality-adjusted life
      year. CONCLUSIONS: The evidence for multidimensional interventions and the
      economic impact of rehabilitation studies is scarce and dominated by breast
      cancer studies. Studies published so far report statistically significant
      benefits for multidimensional interventions over usual care, most notably for the
      outcomes fatigue and physical functioning. An additional benefit of
      multidimensional over monodimensional rehabilitation was not found, but this was
      also sparsely reported on. Available economic evaluations assessed very different
      rehabilitation interventions. Yet, despite low comparability, all showed
      favorable cost-effectiveness ratios. Future studies should focus their designs on
      the comparative effectiveness and cost-effectiveness of multidimensional
      programs.

PMID- 22982581
TI  - The value of ultrasound in detecting extra-axillary regional node involvement in
      patients with advanced breast cancer.
AB  - Assessment of the regional lymphatics is important for accurate staging and
      treatment of breast cancer patients. We sought to determine the role of regional
      ultrasound in providing clinically relevant information. We retrospectively
      analyzed data from patients who were treated curatively in 1996-2006 at The
      University of Texas MD Anderson Cancer Center for clinical stage III breast
      cancer. We compared differences in regional lymph node staging based on
      ultrasound versus mammography and physical examination in the 865 of 1,200
      patients who had external-beam radiation as part of their treatment and regional
      ultrasound studies as part of their initial evaluation. Ultrasound uniquely
      identified additional lymph node involvement beyond the level I or II axilla in
      37% of the patients (325 of 865), leading to a change in clinical nodal stage.
      Ninety-one percent of these abnormalities that could be biopsied (266 or 293)
      were confirmed to contain disease. The sites of additional regional nodal disease
      were: infraclavicular disease, 32% (275 of 865); supraclavicular disease, 16%
      (140 of 865); and internal mammary disease, 11% (98 of 865). All patients with
      involvement in the extra-axillary regional nodal basins received a radiation
      boost to the involved areas >= 10 Gy. Thus, over one third of patients with
      advanced breast cancer had their radiation plan altered by the ultrasound
      findings. Regional ultrasound evaluation in patients with advanced breast cancer
      commonly revealed abnormalities within and beyond the axilla, which changed the
      clinical stage of disease and the radiation treatment strategy. Therefore,
      regional ultrasound is beneficial in the initial staging evaluation for such
      patients.

PMID- 22982582
TI  - Social cognition in borderline personality disorder: evidence for dichotomous
      thinking but no evidence for less complex attributions.
AB  - This experiment investigated social cognition in borderline personality disorder
      (BPD). We tested whether BPD-patients' evaluations of others were characterized
      by splitting, dichotomous thinking, or negativity; and whether they showed less
      complex understanding of others. Participants discussed a problem with three
      alleged mental health worker trainees, performing three interpersonal roles
      (rejecting, accepting and neutral). Participants evaluated trainees in a
      structured response format and in a semi-structured interview. BPD-patients (n =
      18) were compared to Cluster-C personality disorder patients (n = 18) and
      nonpatients (n = 18). From visual analog scales with opposite trait descriptions
      (structured response format) negativity, dichotomous thinking, and splitting
      scores were derived. The interviews were scored by an independent rater on affect
      tone, differentiation, and complexity of attributions. BPD-patients showed, in
      all conditions, and in both response formats, more dichotomous thinking than
      control groups. Evidence for splitting as specific BPD-characteristic was not
      convincing, and more negativity in BPD was only found with the rejecting role and
      structured responses. The interview-based evaluations by BPD-patients could not
      be discriminated from nonpatients in cognitive complexity. Results indicate that
      dichotomous thinking, and not so much splitting, negativity, or less complexity,
      is central in the interpretation of others by BPD-patients. Treatment might
      address dichotomous thinking to reduce BPD-patients' interpersonal problems.

PMID- 22982583
TI  - Unifying concepts in anaerobic respiration: insights from dissimilatory sulfur
      metabolism.
AB  - Behind the versatile nature of prokaryotic energy metabolism is a set of redox
      proteins having a highly modular character. It has become increasingly recognized
      that a limited number of redox modules or building blocks appear grouped in
      different arrangements, giving rise to different proteins and functionalities.
      This modularity most likely reveals a common and ancient origin for these redox
      modules, and is obviously reflected in similar energy conservation mechanisms.
      The dissimilation of sulfur compounds was probably one of the earliest biological
      strategies used by primitive organisms to obtain energy. Here, we review some of
      the redox proteins involved in dissimilatory sulfur metabolism, focusing on
      sulfate reducing organisms, and highlight links between these proteins and others
      involved in different processes of anaerobic respiration. Noteworthy are links to
      the complex iron-sulfur molybdoenzyme family, and heterodisulfide reductases of
      methanogenic archaea. We discuss how chemiosmotic and electron
      bifurcation/confurcation may be involved in energy conservation during sulfate
      reduction, and how introduction of an additional module, multiheme cytochromes c,
      opens an alternative bioenergetic strategy that seems to increase metabolic
      versatility. Finally, we highlight new families of heterodisulfide reductase
      related proteins from non-methanogenic organisms, which indicate a widespread
      distribution for these protein modules and may indicate a more general
      involvement of thiol/disulfide conversions in energy metabolism. This article is
      part of a Special Issue entitled: The evolutionary aspects of bioenergetic
      systems.

PMID- 22982584
TI  - On determining the intracranial sources of visual evoked potentials from scalp
      topography: a reply to Kelly et al. (this issue).
AB  - The cruciform model posits that if a Visual Evoked Potential component originates
      in cortical area V1, then stimuli placed in the upper versus lower visual field
      will generate responses with opposite polarity at the scalp. In our original
      paper (Ales et al., 2010b) we showed that the cruciform model provides an
      insufficient criterion for identifying V1 sources. This conclusion was reached on
      the basis of simulations that used realistic 3D models of early visual areas to
      simulate scalp topographies expected for stimuli of different sizes and shapes
      placed in different field locations. The simulations indicated that stimuli
      placed in the upper and lower visual field produce polarity inverting scalp
      topographies for activation of areas V2 and V3, but not for area V1. As a
      consequence of the non-uniqueness of the polarity inversion criterion, we
      suggested that past studies using the cruciform model had not adequately excluded
      contributions from sources outside V1. In their comment on our paper, Kelly et
      al. (this issue) raise several concerns with this suggestion. They claim that our
      initial results did not use the proper stimulus locations to constitute a valid
      test of the cruciform model. Kelly et al., also contend that the cortical source
      of the initial visually evoked component (C1) can be identified based on latency
      and polarity criteria derived from intracranial recordings in non-human primates.
      In our reply we show that simulations using the suggested critical stimulus
      locations are consistent with our original findings and thus do not change our
      conclusions regarding the use of the polarity inversion criterion. We further
      show that the anatomical assumptions underlying the putatively optimal locations
      are not consistent with available V1 anatomical data. We then address the non
      human primate data, describing how differences in stimuli across studies and
      species confound an effective utilization of the non-human primate data for
      interpreting human evoked potential responses. We also show that, considered more
      broadly, the non-human primate literature shows that multiple visual areas onset
      simultaneously with V1. We suggest several directions for future research that
      will further clarify how to make the best use of scalp data for inferring
      cortical sources.

PMID- 22982585
TI  - A left cerebellar pathway mediates language in prematurely-born young adults.
AB  - Preterm (PT) subjects are at risk for developmental delay, and task-based studies
      suggest that developmental disorders may be due to alterations in neural
      connectivity. Since emerging data imply the importance of right cerebellar
      function for language acquisition in typical development, we hypothesized that PT
      subjects would have alternate areas of cerebellar connectivity, and that these
      areas would be responsible for differences in cognitive outcomes between PT
      subjects and term controls at age 20 years. Nineteen PT and 19 term control young
      adults were prospectively studied using resting-state functional MRI (fMRI) to
      create voxel-based contrast maps reflecting the functional connectivity of each
      tissue element in the grey matter through analysis of the intrinsic connectivity
      contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects
      identified a region of interest that was used for subsequent seed-based
      connectivity analyses. Subjects underwent standardized language testing, and
      correlations with cognitive outcomes were assessed. There were no differences in
      gender, hand preference, maternal education, age at study, or Peabody Picture
      Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated
      increased tissue connectivity in the biventer, simple and quadrangular lobules of
      the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses
      from these regions demonstrated alterations in connectivity from L cerebellum to
      both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For
      PTs but not term controls, there were significant positive correlations between
      these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454,
      p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472,
      p=0.04). These data suggest the presence of a left cerebellar language circuit in
      PT subjects at young adulthood. These findings may represent either a delay in
      maturation or the engagement of alternative neural pathways for language in the
      developing PT brain.

PMID- 22982586
TI  - Encoding and recall of finger sequences in experienced pianists compared with
      musically naive controls: a combined behavioral and functional imaging study.
AB  - Long-term intensive sensorimotor training alters functional representation of the
      motor and sensory system and might even result in structural changes. However,
      there is not much knowledge about how previous training impacts learning transfer
      and functional representation. We tested 14 amateur pianists and 15 musically
      naive participants in a short-term finger sequence training procedure, differing
      considerably from piano playing and measured associated functional representation
      with functional magnetic resonance imaging. The conditions consisted of encoding
      a finger sequence indicated by hand symbols ("sequence encoding") and
      subsequently replaying the sequence from memory, both with and without auditory
      feedback ("sequence retrieval"). Piano players activated motor areas and the
      mirror neuron system more strongly than musically naive participants during
      encoding. When retrieving the sequence, musically naive participants showed
      higher activation in similar brain areas. Thus, retrieval activations of naive
      participants were comparable to encoding activations of piano players, who during
      retrieval performed the sequences more accurately despite lower motor
      activations. Interestingly, both groups showed primary auditory activation even
      during sequence retrieval without auditory feedback, supporting previous reports
      about coactivation of the auditory cortex after learned association with motor
      performance. When playing with auditory feedback, only pianists lateralized to
      the left auditory cortex. During encoding activation in left primary
      somatosensory cortex in the height of the finger representations had a predictive
      value for increased motor performance later on (error rates). Contrarily,
      decreased performance was associated with increased visual cortex activation
      during encoding. Our study extends previous reports about training transfer of
      motor knowledge resulting in superior training effects in musicians. Performance
      increase went along with activity in motor areas and the mirror neuron network
      during pattern encoding.

PMID- 22982588
TI  - The exclusive use of flow cytometry to evaluate the antibiotic-susceptibility.
AB  - BACKGROUND: Live and injured bacteria cannot be successfully discriminated using
      flow cytometric methods (FCM) with commercial live/dead staining agents because
      injured cells have intact cell membranes and are counted as live cells. We
      previously reported that photoactivated ethidium monoazide (EMA) directly cleaves
      bacterial DNA both in vivo and in vitro (Microbiol. Immunol. 51:763-775, 2007).
      METHODS: We report that EMA cleaves the chromosomal DNA of antibiotic-injured,
      but not live, Listeria monocytogenes. The combination of FCM and EMA treatment
      was evaluated as a rapid method to discriminate between live and antibiotic
      injured L. monocytogenes. Additionally, we evaluated our methodology using blood
      from pediatric patients infected with other gram-negative and gram-positive
      bacteria. RESULTS: For antibiotic-injured, but not live, L. monocytogenes in
      blood, photoactivated EMA suppressed SYTO9 staining, as the SYTO9 staining of the
      antibiotic-injured L. monocytogenes was weak compared with that of live cells.
      Similarly, the rapid and clear discrimination between live and injured bacteria
      (gram-negative and gram-positive) was performed using the blood of pediatric
      patients administered antibiotics. CONCLUSIONS: The combination of FCM with EMA
      treatment is a rapid method for evaluating the susceptibility of live pathogens
      in infants with bacteremia without the need for bacterial culture. GENERAL
      SIGNIFICANCE: This assay is more rapid than other currently available techniques
      due to the elimination of the time-consuming culture step and could be used in
      clinical settings to rapidly determine the success of antibiotic treatment in
      pediatric bacteremia through the discrimination of injured (i.e., susceptible to
      the administered antibiotics) and live pathogens.

PMID- 22982590
TI  - Creative cognition and the brain: dissociations between frontal, parietal
      temporal and basal ganglia groups.
AB  - The objective of the study was to investigate creativity in relation to brain
      function by assessing creative thinking in various neurological populations.
      Several measures were employed to assess different facets of creative thinking in
      clinical groups with frontal lobe, basal ganglia or parietal-temporal lesions
      relative to matched healthy control participants. The frontal group was
      subdivided into frontolateral, frontopolar and frontal-extensive groups.
      Hierarchical regression analyses were employed to assess the significance levels
      associated with the effects after accounting for IQ differences between the
      groups. Findings were only considered noteworthy if they at least suggested the
      presence of a strong trend and were accompanied by medium to large effect sizes.
      The parietal-temporal and frontolateral groups revealed poorer overall
      performance with the former demonstrating problems with fluency related measures,
      whereas the latter were also less proficient at producing original responses. In
      contrast, the basal ganglia and frontopolar groups demonstrated superior
      performance in the ability to overcome the constraints imposed by salient
      semantic distractors when generating creative responses. In summary, the
      dissociations in the findings reveal the selective involvement of different brain
      regions in diverse aspects of creativity. Lesion location posed selective
      limitations on the ability to generate original responses in different contexts,
      but not on the ability to generate relevant responses, which was compromised in
      most patient groups. The noteworthy findings from this exploratory study of
      enhanced performance in specific aspects of creative cognition following brain
      damage are discussed with reference to the generic idea that superior creative
      ability can result from altered brain function.

PMID- 22982589
TI  - Modulation of methamphetamine-induced nitric oxide production by neuropeptide Y
      in the murine striatum.
AB  - Methamphetamine (METH) is a potent stimulant that induces both acute and long
      lasting neurochemical changes in the brain including neuronal cell loss. Our
      laboratory demonstrated that the neuropeptide substance P enhances the striatal
      METH-induced production of nitric oxide (NO). In order to better understand the
      role of the striatal neuropeptides on the METH-induced production of NO, we used
      agonists and antagonists of the NPY (Y1R and Y2R) receptors infused via
      intrastriatal microinjection followed by a bolus of METH (30 mg/kg, ip) and
      measured 3-NT immunofluorescence, an indirect index of NO production. One
      striatum received pharmacological agent while the contralateral striatum received
      aCSF and served as control. NPY receptor agonists dose dependently attenuated the
      METH-induced production of striatal 3-NT. Conversely, NPY receptor antagonists
      had the opposite effect. Moreover, METH induced the accumulation of cyclic GMP
      and activated caspase-3 in approximately 18% of striatal neurons, a phenomenon
      that was attenuated by pre-treatment with NPY2 receptor agonist. Lastly, METH
      increased the levels of striatal preproneuropeptide Y mRNA nearly five-fold 16 h
      after injection as determined by RT-PCR, suggesting increased utilization of the
      neuropeptide. In conclusion, NPY inhibits the METH-induced production of NO in
      striatal tissue. Consequently, production of this second messenger induces the
      accumulation of cyclic GMP and activated caspase-3 in some striatal neurons, an
      event that may precede the apoptosis of some striatal neurons.

PMID- 22982591
TI  - Graph theoretical analysis of EEG functional connectivity during music
      perception.
AB  - The present study evaluated the effect of music on large-scale structure of
      functional brain networks using graph theoretical concepts. While most studies on
      music perception used Western music as an acoustic stimulus, Guqin music,
      representative of Eastern music, was selected for this experiment to increase our
      knowledge of music perception. Electroencephalography (EEG) was recorded from non
      musician volunteers in three conditions: Guqin music, noise and silence
      backgrounds. Phase coherence was calculated in the alpha band and between all
      pairs of EEG channels to construct correlation matrices. Each resulting matrix
      was converted into a weighted graph using a threshold, and two network measures:
      the clustering coefficient and characteristic path length were calculated. Music
      perception was found to display a higher level mean phase coherence. Over the
      whole range of thresholds, the clustering coefficient was larger while listening
      to music, whereas the path length was smaller. Networks in music background still
      had a shorter characteristic path length even after the correction for
      differences in mean synchronization level among background conditions. This
      topological change indicated a more optimal structure under music perception.
      Thus, prominent small-world properties are confirmed in functional brain
      networks. Furthermore, music perception shows an increase of functional
      connectivity and an enhancement of small-world network organizations.

PMID- 22982587
TI  - Signaling mechanisms regulating adult neural stem cells and neurogenesis.
AB  - BACKGROUND: Adult neurogenesis occurs throughout life in discrete regions of the
      mammalian brain and is tightly regulated via both extrinsic environmental
      influences and intrinsic genetic factors. In recent years, several crucial
      signaling pathways have been identified in regulating self-renewal,
      proliferation, and differentiation of neural stem cells, as well as migration and
      functional integration of developing neurons in the adult brain. SCOPE OF REVIEW:
      Here we review our current understanding of signaling mechanisms, including Wnt,
      notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic
      proteins, neurotransmitters, transcription factors, and epigenetic modulators,
      and crosstalk between these signaling pathways in the regulation of adult
      neurogenesis. We also highlight emerging principles in the vastly growing field
      of adult neural stem cell biology and neural plasticity. MAJOR CONCLUSIONS:
      Recent methodological advances have enabled the field to identify signaling
      mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading
      to a better characterization of both cell-intrinsic and environmental cues
      defining the neurogenic niche. Significant questions related to niche cell
      identity and underlying regulatory mechanisms remain to be fully addressed and
      will be the focus of future studies. GENERAL SIGNIFICANCE: A full understanding
      of the role and function of individual signaling pathways in regulating neural
      stem cells and generation and integration of newborn neurons in the adult brain
      may lead to targeted new therapies for neurological diseases in humans. This
      article is part of a Special Issue entitled Biochemistry of Stem Cells.

PMID- 22982592
TI  - Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta
      peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway.
AB  - One hallmark of Alzheimer's disease (AD) is amyloid-beta (Abeta) deposition,
      which can initiate a cascade of oxidative events that may result in neuronal
      death. The present study aimed to investigate the protective effects of
      gastrodin, a phenolic compound which shows antioxidant activity, on Abeta(1-42)
      induced neurotoxicity and the underlying mechanism for this neuroprotection.
      Results indicate that Abeta(1-42)-induced neuronal toxicity as measured by cell
      viability, which was correlated with decreased catalase (CAT) content and
      superoxide dismutase (SOD) activity. Pre-treatment of primary hippocampal neurons
      with gastrodin significantly attenuated Abeta(1-42)-induced neurotoxicity and
      changes in SOD and CAT, and upregulated gene expression of nuclear factor
      erythroid 2-related factor 2 (Nrf2) and extracellular signal-regulated kinases 1
      and 2 (ERK1/2) phosphorylation. Pharmacological blockade of ERK1/2 abrogation
      this action of gastrodin. The ERK1/2 pathway may be involved in the
      neuroprotective effect of gastrodin against Abeta(1-42)-induced oxidative in
      primary cultured rat hippocampal neurons. These findings suggest that gastrodin
      could be of importance for the treatment of AD and other oxidative stress-related
      diseases.

PMID- 22982593
TI  - Attenuation of axonal injury and oxidative stress by edaravone protects against
      cognitive impairments after traumatic brain injury.
AB  - Traumatic axonal injury (TAI), a feature of traumatic brain injury (TBI),
      progressively evolves over hours through impaired axonal transport and is thought
      to be a major contributor to cognitive dysfunction. In spite of various studies
      suggesting that pharmacologic or physiologic interventions might reduce TAI,
      clinical neuroprotective treatments are still unavailable. Edaravone, a free
      radical scavenger, has been shown to exert neuroprotective effects in animal
      models of several brain disorders. In this study, to evaluate whether edaravone
      suppresses TAI following TBI, mice were subjected to weight drop injury and had
      either edaravone (3.0mg/kg) or saline administered intravenously immediately
      after impact. Axonal injury and oxidative stress were assessed using
      immunohistochemistry with antibodies against amyloid precursor protein, a marker
      of impaired axonal transport, and with 8-hydroxy-2'-deoxyguanosine, a marker of
      oxidative DNA damage. Edaravone significantly suppressed axonal injury and
      oxidative stress in the cortex, corpus callosum, and hippocampus 24h after
      injury. The neuroprotective effects of edaravone were observed in mice receiving
      1.0, 3.0, or 10mg/kg of edaravone immediately after impact, but not after
      0.3mg/kg of edaravone. With treatment 1h after impact, axonal injury was also
      significantly suppressed and this therapeutic effect persisted up to 6h after
      impact. Furthermore, behavioral tests performed 9 days after injury showed memory
      deficits in saline-treated traumatized mice, which were not evident in the
      edaravone-treated group. These results suggest that edaravone protects against
      memory deficits following TBI and that this protection is mediated by suppression
      of TAI and oxidative stress.

PMID- 22982594
TI  - PPARdelta agonist GW501516 prevents uncoupling of endothelial nitric oxide
      synthase in cerebral microvessels of hph-1 mice.
AB  - Peroxisome proliferator-activated receptor delta (PPARdelta) is ubiquitously
      expressed in the vasculature, including cerebral circulation. The role of
      PPARdelta in metabolism of tetrahydrobiopterin (BH4) has not been studied in the
      cerebral microvasculature. In the present study, the effects of PPARdelta agonist
      GW501516 on uncoupling of endothelial nitric oxide synthase (eNOS) were
      determined in cerebral microvessels of BH4-deficient hph-1 mice. Wild-type
      (B6CBA) and hph-1 mice were orally gavaged with a selective PPARdelta activator,
      GW501516 (2 mg/kg/day) for 14 days, and thereafter, cerebral microvessels were
      isolated and studied. Treatment of hph-1 mice with GW501516 significantly reduced
      oxidation of BH4 and increased the ratio of BH4 to 7,8-BH2 (P<0.05, n=6-9).
      Attenuation of L-NAME-inhibitable superoxide anion levels by GW501516
      demonstrated that activation of PPARdelta might prevent uncoupling of endothelial
      nitric oxide synthase (eNOS, P<0.05, n=6-9). Western blotting studies
      demonstrated that GW501516 selectively increased the endothelial expressions of
      CuZn superoxide dismutase (P<0.05, n=6-9) and catalase (P<0.05, n=6-8). PPARdelta
      activation increased the total nitrite and nitrate (NO2+NO3) content in cerebral
      microvessels (P<0.05, n=6). Obtained results suggest that in vivo activation of
      PPARdelta prevents eNOS uncoupling, restores bioavailability of NO and may help
      preserve endothelial function in the BH4-deficient cerebral circulation.

PMID- 22982595
TI  - Morg1(+/-) heterozygous mice are protected from experimentally induced focal
      cerebral ischemia.
AB  - Focal cerebral ischemia (stroke) and reperfusion injury leads to acute and
      chronic brain damage. The increase of the hypoxia-inducible transcription factor
      alpha (HIF-alpha), an important transcription factor for several genes, may
      attenuate ischemic brain injury. We recently identified a new WD-repeat protein
      designated Morg1 (MAPK organizer 1) that interacts with prolyl hydroxylase 3
      (PHD3), an important enzyme involved in the regulation of HIF-1alpha and HIF
      2alpha expression. While homozygous Morg1(-/-) mice are embryonically lethal,
      heterozygous Morg1(+/-) mice have a normal phenotype. Brain vasculature as well
      as systolic blood pressure in Morg1(+/-) mice were indistinguishable from wild
      type (WT) animals. We show here that Morg1(+/-) mice were partially protected
      from cerebral ischemia/reperfusion injury in comparison to WT (Morg1(+/+))
      animals using the middle cerebral artery occlusion model (MCAO). Morg1(+/-) mice
      compared with WT animals revealed a significantly reduced infarct volume as
      detected by Nissl and Map 2 staining despite a similar restriction of blood flow
      in both mice genotypes as measured by laser Doppler flowmetry.
      Immunohistochemistry revealed specific Morg1 expression in reactive astrocytes in
      the ipsilateral (ischemic) hemisphere in Morg1(+/-) and WT mice, especially in
      the penumbral regions. In the contralateral hemisphere, Morg1 was not detectable.
      Furthermore, Morg1 mRNA expression was significantly enhanced in the ischemic
      brain of WT, but not in ischemic brain tissue obtained from Morg1(+/-) animals.
      However, HIF-1alpha was expressed with the same intensity in Morg1(+/-) and WT
      mice with no difference between the ipsilateral and contralateral hemispheres. No
      positive staining for HIF-2alpha was found in ischemic (ipsilateral) and non
      ischemic (contralateral) brain regions in Morg1(+/+) and Morg1(+/-) mice. Almost
      no PHD3 staining was found in the contralateral hemispheres of either WT or
      heterozygous Morg1(+/-) mice. Transcript expression for the HIF1alpha-dependent
      genes erythropoietin (Epo) and vascular endothelial growth factor 164 (VEGF 164)
      were significantly reduced in the ischemic brain from Morg1(+/-) mice. Positive
      staining for PHD3 in the ipsilateral hemisphere of WT mice was suggested to occur
      in astrocytes. A compensatory increase in Morg1 expression in astrocytes in the
      penumbra may negatively influence infarct volume. It appears that these effects
      are independent of the PHD3-HIF1alpha axis.

PMID- 22982596
TI  - Detection of reactive oxygen species derived from the family of NOX NADPH
      oxidases.
AB  - NADPH oxidases (NOX) are superoxide anion radical (O(2)(-*))-generating enzymes.
      They form a family of seven members, each with a specific tissue distribution.
      They function as electron transport chains across membranes, using NADPH as
      electron donor to reduce molecular oxygen to O(2)(-*). NOX have multiple
      biological functions, ranging from host defense to inflammation and cellular
      signaling. Measuring NOX activity is crucial in understanding the roles of these
      enzymes in physiology and pathology. Many of the methods used to measure NOX
      activity are based on the detection of small molecules that react with NOX
      generated O(2)(-*) or its direct dismutation product hydrogen peroxide (H(2)O(2))
      to form fluorescent, luminescent, or colored products. Initial techniques were
      developed to measure the activity of the phagocyte isoform NOX2 during the
      oxidative burst of stimulated polymorphonuclear leukocytes, which generate large
      quantities of O(2)(-*). However, other members of the NOX family generate much
      less O(2)(-*) and hence H(2)O(2), and their activity is difficult to distinguish
      from other sources of these reactive species. In addition, O(2)(-*) and H(2)O(2)
      are reactive molecules and most probes are prone to artifacts and therefore
      should be used with appropriate controls and the data carefully interpreted. This
      review gives an overview of current methods used to measure NOX activity and NOX
      derived O(2)(-*) and H(2)O(2) in cells, tissues, isolated systems, and living
      organisms, describing the advantages and caveats of many established methods with
      emphasis on more recent technologies and future perspectives.

PMID- 22982597
TI  - Nitroxides attenuate carrageenan-induced inflammation in rat paws by reducing
      neutrophil infiltration and the resulting myeloperoxidase-mediated damage.
AB  - Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) and other cyclic
      nitroxides have been shown to inhibit the chlorinating activity of
      myeloperoxidase (MPO) in vitro and in cells. To examine whether nitroxides
      inhibit MPO activity in vivo we selected acute carrageenan-induced inflammation
      on the rat paw as a model. Tempol and three more hydrophobic 4-substituted
      derivatives (4-azido, 4-benzenesulfonyl, and 4-(4-phenyl-1H-1,2,3-triazol-1-yl))
      were synthesized, and their ability to inhibit the in vitro chlorinating activity
      of MPO and carrageenan-induced inflammation in rat paws was evaluated. All of the
      tested nitroxides inhibited the chlorinating activity of MPO in vitro with
      similar IC(50) values (between 1.5 and 1.8 MUM). In vivo, the attenuation of
      carrageenan-induced inflammation showed some correlation with the lipophilicity
      of the nitroxide at early time points but the differences in the effects were
      small (<2-fold) compared with the differences in lipophilicity (>200-fold). No
      inhibition of MPO activity in vivo was evident because the levels of MPO activity
      in rat paws correlated with the levels of MPO protein. Likewise, paw edema,
      levels of nitrated and oxidized proteins, and levels of plasma exudation
      correlated with the levels of MPO protein in the paws of the animals that were
      untreated or treated with the nitroxides. The effects of the nitroxides in vivo
      were compared with those of 4-aminobenzoic hydrazide and of colchicine. Taken
      together, the results indicate that nitroxides attenuate carrageenan-induced
      inflammation mainly by reducing neutrophil migration and the resulting MPO
      mediated damage. Accordingly, tempol was shown to inhibit rat neutrophil
      migration in vitro.

PMID- 22982598
TI  - Glutathione redox cycle dysregulation in Huntington's disease knock-in striatal
      cells.
AB  - Huntington's disease (HD) is a CAG repeat disorder affecting the HD gene, which
      encodes for huntingtin (Htt) and is characterized by prominent cell death in the
      striatum. Oxidative stress was previously implicated in HD neurodegeneration, but
      the role of the major endogenous antioxidant system, the glutathione redox cycle,
      has been less studied following expression of full-length mutant Htt (FL-mHtt).
      Thus, in this work we analyzed the glutathione system in striatal cells derived
      from HD knock-in mice expressing mutant Htt versus wild-type cells. Mutant cells
      showed increased intracellular reactive oxygen species (ROS) and caspase-3
      activity, which were significantly prevented following treatment with glutathione
      ethyl ester. Interestingly, mutant cells exhibited an increase in intracellular
      levels of both reduced and oxidized forms of glutathione, and enhanced activities
      of glutathione peroxidase (GPx) and glutathione reductase (GRed). Furthermore,
      glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT)
      activities were also increased in mutant cells. Nevertheless, glutamate-cysteine
      ligase (GCL) and glutathione synthetase (GS) activities and levels of GCL
      catalytic subunit were decreased in cells expressing FL-mHtt, highly suggesting
      decreased de novo synthesis of glutathione. Enhanced intracellular total
      glutathione, despite decreased synthesis, could be explained by decreased
      extracellular glutathione in mutant cells. This occurred concomitantly with
      decreased mRNA expression levels and activity of the multidrug resistance protein
      1 (Mrp1), a transport protein that mediates cellular export of glutathione
      disulfide and glutathione conjugates. Additionally, inhibition of Mrp1 enhanced
      intracellular GSH in wild-type cells only. These data suggest that FL-mHtt
      affects the export of glutathione by decreasing the expression of Mrp1. Data
      further suggest that boosting of GSH-related antioxidant defense mechanisms
      induced by FL-mHtt is insufficient to counterbalance increased ROS formation and
      emergent apoptotic features in HD striatal cells.

PMID- 22982599
TI  - Stability and membrane interactions of an autotransport protein: MD simulations
      of the Hia translocator domain in a complex membrane environment.
AB  - Hia is a trimeric autotransporter found in the outer membrane of Haemphilus
      influenzae. The X-ray structure of Hia translocator domain revealed each monomer
      to consist of an alpha-helix connected via a loop to a 4-stranded beta-sheet,
      thus the topology of the trimeric translocator domain is a 12-stranded beta
      barrel containing 3 alpha-helices that protrude from the mouth of the beta-barrel
      into the extracellular medium. Molecular dynamics simulations of the Hia monomer
      and trimer have been employed to explore the interactions between the helices,
      beta-barrel and connecting loops that may contribute to the stability of the
      trimer. In simulations of the Hia monomer we show that the central alpha-helix
      may stabilise the fold of the 4-stranded beta-sheet. In simulations of the Hia
      trimer, a H-bond network involving residues in the beta-barrel, alpha-helices and
      loops has been identified as providing stability for the trimeric arrangement of
      the monomers. Glutamine residues located in the loops connecting the alpha
      helices to the beta-barrel are orientated in a triangular arrangement such that
      each forms 2 hydrogen bonds to each of the corresponding glutamines in the other
      loops. In the absence of the loops, the beta-barrel becomes distorted.
      Simulations show that while the trimeric translocator domain beta-barrel is
      inherently flexible, it is unlikely to accommodate the passenger domain in a
      folded conformation. Simulations of Hia in an asymmetric model of the outer
      membrane have revealed membrane-protein interactions that anchor the protein
      within its native membrane environment.

PMID- 22982600
TI  - Resistance to diamide insecticides in diamondback moth, Plutella xylostella
      (Lepidoptera: Plutellidae) is associated with a mutation in the membrane-spanning
      domain of the ryanodine receptor.
AB  - Diamide insecticides such as chlorantraniliprole and flubendiamide are a new
      class of insecticide that selectively target insect ryanodine receptors (RyR), a
      distinct class of homo-tetrameric calcium release channels which play a pivotal
      role in calcium homeostasis in numerous cell types. Resistance to these
      insecticides has recently been reported in the diamondback moth, Plutella
      xylostella (Lepidoptera: Plutellidae), a global lepidopteran pest of cruciferous
      crops. In the present study a region of the gene encoding the proposed diamide
      binding site of the RyR from P. xylostella collected from the Philippines and
      Thailand and found to be over 200-fold resistant to both chlorantraniliprole and
      flubendiamide compared to susceptible strains, were amplified by RT-PCR and
      sequenced. Comparison of the sequence with those from several susceptible
      reference strains revealed non-synonymous mutations in each of the resistant
      strains that in both cases lead to a glycine to glutamic acid substitution
      (G4946E) in the protein. The independent evolution of the same amino acid
      substitution within a highly conserved region of the proposed diamide binding
      site in two geographically separated resistant strains of P. xylostella strongly
      suggests a causal association with diamide resistance. Furthermore we designed a
      pyrosequencing-based diagnostic assay for resistance monitoring purposes that can
      be used to detect the G4946E mutation in field-collected samples of diamondback
      moth. The implications of the reported findings for resistance management
      strategies are discussed.

PMID- 22982601
TI  - Targeted mutagenesis of the Clostridium acetobutylicum acetone-butanol-ethanol
      fermentation pathway.
AB  - The production of the chemical solvents acetone and butanol by the bacterium
      Clostridium acetobutylicum was one of the first large-scale industrial processes
      to be developed, and in the first part of the last century ranked second in
      importance only to ethanol production. After a steep decline in its industrial
      use, there has been a recent resurgence of interest in the acetone-butanol
      ethanol (ABE) fermentation process, with a particular emphasis on butanol
      production. In order to generate strains suitable for efficient use on an
      industrial scale, metabolic engineering is required to alter the AB ratio in
      favour of butanol, and eradicate the production of unwanted products of
      fermentation. Using ClosTron technology, a large-scale targeted mutagenesis in C.
      acetobutylicum ATCC 824 was carried out, generating a set of 10 mutants,
      defective in alcohol/aldehyde dehydrogenases 1 and 2 (adhE1, adhE2), butanol
      dehydrogenases A and B (bdhA, bdhB), phosphotransbutyrylase (ptb), acetate kinase
      (ack), acetoacetate decarboxylase (adc), CoA transferase (ctfA/ctfB), and a
      previously uncharacterised putative alcohol dehydrogenase (CAP0059). However,
      inactivation of the main hydrogenase (hydA) and thiolase (thl) could not be
      achieved. Constructing such a series of mutants is paramount for the acquisition
      of information on the mechanism of solvent production in this organism, and the
      subsequent development of industrial solvent producing strains. Unexpectedly,
      bdhA and bdhB mutants did not affect solvent production, whereas inactivation of
      the previously uncharacterised gene CAP0059 resulted in increased acetone,
      butanol, and ethanol formation. Other mutants showed predicted phenotypes,
      including a lack of acetone formation (adc, ctfA, and ctfB mutants), an inability
      to take up acids (ctfA and ctfB mutants), and a much reduced acetate formation
      (ack mutant). The adhE1 mutant in particular produced very little solvents,
      demonstrating that this gene was indeed the main contributor to ethanol and
      butanol formation under the standard batch culture conditions employed in this
      study. All phenotypic changes observed could be reversed by genetic
      complementation, with exception of those seen for the ptb mutant. This mutant
      produced around 100 mM ethanol, no acetone and very little (7 mM) butanol. The
      genome of the ptb mutant was therefore re-sequenced, together with its parent
      strain (ATCC 824 wild type), and shown to possess a frameshift mutation in the
      thl gene, which perfectly explained the observed phenotype. This finding
      reinforces the need for mutant complementation and Southern Blot analysis (to
      confirm single ClosTron insertions), which should be obligatory in all further
      ClosTron applications.

PMID- 22982602
TI  - Postnatal mammalian retinal development: quantitative data and general rules.
AB  - This article is aimed at providing comparative quantitative data about postnatal
      mammalian retina development, and at searching for some general rules at both the
      descriptive and the mechanistic level. In mammals the eye continues to grow, and
      the retina continues to expand, much after the end of retinal cytogenesis. Thus,
      although the total number of retinal cells remains constant after cessation of
      mitotic activity (and the end of 'physiological cell death'), the retinal surface
      area increases by a factor of two or more. In most mammals, ocular growth exceeds
      retinal expansion: the neural retina lines 70-80% of the inner ocular surface at
      the beginning but only about 40-60% in adults. Differential local expansion of
      the retina (the peripheral area increases more than the central one) can be
      explained by 'passive stretching' of the retinal tissue by the growing eyeball;
      it depends on the different biomechanical properties of the peripheral vs.
      central retinal tissue. The increasing retinal surface area allows for a re
      distribution of cells such that the thickness of the (particularly, outer)
      nuclear layer(s) decreases proportional to the areal expansion. This causes a
      considerable developmental reduction of the number of cell nuclei 'stacked above
      each other' by a factor of more than two, and requires a translocation of the
      somata against their neighbors. We provide a physico-mathematical model of these
      oblique 'down-sliding' movements of the photoreceptor cell somata along the
      Muller cell process in the center of their columnar cell unit.

PMID- 22982603
TI  - Radiation hazard indices of soil and water samples in Northern Malaysian
      Peninsula.
AB  - The radioactivity quantity and quality were determined in soil and water samples
      in Northern Malaysian Peninsula (NMP) using HPGe spectroscopy and GR-135
      spectrometer. The (226)Ra, (232)Th and (40)K concentrations in soil samples are
      57+/-2, 68+/-4 and 427+/-17 Bq kg(-1), respectively, whereas in water samples
      were found to be 2.86+/-0.79, 3.78+/-1.73 and 152+/-12 Bq l(-1), respectively.
      These concentrations are within those reported from literature in other countries
      in the world. The radiological hazard indices of the samples were also
      calculated. The mean values obtained from soil samples are 186 Bq kg(-1), 88 nGy
      h(-1), 108 MUSv y(-1), 0.50 and 0.65 for Radium Equivalent Activity (Ra(eq)),
      Absorbed Dose Rates (D(R)), Annual Effective Dose Rates (ED), External Hazard
      Index (H(ex)) and Internal Hazard Index (H(in)) respectively, whereas, for water
      samples were found to be 20, 10, 13, 0.05 and 0.06, respectively. All the health
      hazard indices are well below their recommended limits, except in two soil
      sampling sites which were found to be (*)025 (1.1 H(ex)) and (*)026 (1.1 H(ex),
      1.6 H(in)). The calculated and the measured gamma dose rates had a good
      correlation coefficient, R=0.88. Moreover, the average value radon is 20 (in the
      range of 7-64) Bq m(-3), a positive correlation (R=0.81) was observed between the
      (222)Rn and (226)Ra concentrations in samples measured by the SNC continuous
      radon monitor (model 1029, Sun Nuclear Corporation) and HPGe detector,
      respectively. Some soils in this study with H(in) and H(ex)<1 are suitable for
      use in agriculture and as building materials. Also, in this study H(in) and
      H(ex)<1 for water samples, therefore, water after processing and filtration is
      safe and suitable for use in household and industrial purposes.

PMID- 22982604
TI  - The influence of emotional words on sentence processing: electrophysiological and
      behavioral evidence.
AB  - Whereas most previous studies on emotion in language have focussed on single
      words, we investigated the influence of the emotional valence of a word on the
      syntactic and semantic processes unfolding during sentence comprehension, by
      means of event-related brain potentials (ERP). Experiment 1 assessed how
      positive, negative, and neutral adjectives that could be either syntactically
      correct or incorrect (violation of number agreement) modulate syntax-sensitive
      ERP components. The amplitude of the left anterior negativity (LAN) to
      morphosyntactic violations increased in negative and decreased in positive words
      in comparison to neutral words. In Experiment 2, the same sentences were
      presented but positive, negative, and neutral adjectives could be either
      semantically correct or anomalous given the sentence context. The N400 to
      semantic anomalies was not significantly affected by the valence of the violating
      word. However, positive words in a sentence seemed to influence semantic
      correctness decisions, also triggering an apparent N400 reduction irrespective of
      the correctness value of the word. Later linguistic processes, as reflected in
      the P600 component, were unaffected in either experiment. Overall, our results
      indicate that emotional valence in a word impacts the syntactic and semantic
      processing of sentences, with differential effects as a function of valence and
      domain.

PMID- 22982605
TI  - Differential effects of amphetamine and haloperidol on temporal reproduction:
      dopaminergic regulation of attention and clock speed.
AB  - Healthy volunteers were tested on 7-s and 17-s peak-interval timing procedures
      following d-amphetamine (20mg-oral), haloperidol (2mg-oral), and placebo
      treatments in order to assess the dopaminergic regulation of temporal processing.
      Individual differences were observed in the drug effects such that two different
      patterns of timing behavior emerged. In the first pattern, d-amphetamine produced
      proportional leftward shifts of the timing functions while haloperidol produced
      proportional rightward shifts. This symmetrical pattern of results suggests that
      clock speed is regulated by the effective level of dopamine, i.e., d-amphetamine
      increases clock speed and haloperidol decreases clock speed. The second pattern
      was the opposite of the first pattern and was revealed by d-amphetamine producing
      proportional rightward shifts of the timing functions while haloperidol produced
      no reliable effect. This asymmetrical pattern of results is consistent with an
      explanation in which attention toward the stimulant-induced euphoria produced by
      d-amphetamine diminishes the attentional resources available for temporal
      processing, thereby diluting any drug-induced changes in clock speed. The result
      of increased competition and time-sharing between these two dimensions (e.g.,
      attention towards feelings of euphoria versus attention towards the passage of
      time) leads to the underestimation/overproduction of temporal intervals.
      Interestingly, participants that displayed the 'clock-speed' pattern liked d
      amphetamine significantly less than participants that displayed the 'attention'
      pattern and were more variable in a simple reaction time task than other
      participants. These results suggest that individuals with a higher degree of
      sensitivity to time are also more sensitive to their feelings of stimulant
      induced euphoria and drug liking-suggesting that internal clock and reward
      pathways share common dopaminergic pathways.

PMID- 22982606
TI  - Speech acoustic markers of early stage and prodromal Huntington's disease: a
      marker of disease onset?
AB  - Speech disturbances (e.g., altered prosody) have been described in symptomatic
      Huntington's Disease (HD) individuals, however, the extent to which speech
      changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The
      speech of individuals carrying the mutant HTT gene is a
      behavioural/motor/cognitive marker demonstrating some potential as an objective
      indicator of early HD onset and disease progression. Speech samples were acquired
      from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD)
      and 15 matched controls. Participants read a passage, produced a monologue and
      said the days of the week. Data were analysed acoustically for measures of
      timing, frequency and intensity. There was a clear effect of group across most
      acoustic measures, so that speech performance differed in-line with disease
      progression. Comparisons across groups revealed significant differences between
      the control and the early stage HD group on measures of timing (e.g., speech
      rate). Participants carrying the mutant HTT gene presented with slower rates of
      speech, took longer to say words and produced greater silences between and within
      words compared to healthy controls. Importantly, speech rate showed a significant
      correlation to burden of disease scores. The speech of early stage HD differed
      significantly from controls. The speech of PreHD, although not reaching
      significance, tended to lie between the performance of controls and early stage
      HD. This suggests that changes in speech production appear to be developing prior
      to diagnosis.

PMID- 22982607
TI  - Exploring the content and quality of episodic future simulations in semantic
      dementia.
AB  - Semantic dementia (SD) is a progressive neurodegenerative disorder characterised
      by the amodal loss of semantic knowledge in the context of relatively preserved
      recent episodic memory. Recent studies have demonstrated that despite relatively
      intact episodic memory the capacity for future simulation in SD is profoundly
      impaired, resulting in an asymmetric profile where past retrieval is
      significantly better than future simulation (referred to as a past>future
      effect). Here, we sought to identify the origins of this asymmetric profile by
      conducting a fine-grained analysis of the contextual details provided during past
      retrieval and future simulation in SD. Participants with SD (n=14), Alzheimer's
      disease (n=11), and healthy controls (n=14) had previously completed an
      experimental past-future interview in which they generated three past events from
      the previous year, and three future events in the next year, and provided
      subjective qualitative ratings of vividness, emotional valence, emotional
      intensity, task difficulty, and personal significance for each event described.
      Our results confirmed the striking impairment for future simulation in SD,
      despite a relative preservation of past episodic retrieval. Examination of the
      contextual details provided for past memories and future simulations revealed
      significant impairments irrespective of contextual detail type for future
      simulations in SD, and demonstrated that the future thinking deficit in this
      cohort was driven by a marked decline in the provision of internal (episodic)
      event details. In contrast with this past>future effect for internal event
      details, SD patients displayed a future>past effect for external (non-episodic)
      event details. Analyses of the qualitative ratings provided for past and future
      events indicated that SD patients' phenomenological experience did not differ
      between temporal conditions. Our findings underscore the fact that successful
      extraction of episodic elements from the past is not sufficient for the
      generation of novel future simulations in SD. The notable disconnect between
      objective task performance and patients' subjective experience during future
      simulation likely reflects the tendency of SD patients to recast entire past
      events into the future condition. Accordingly, the familiarity of the
      recapitulated details results in similar ratings of vividness and emotionality
      across temporal conditions, despite marked differences in the richness of
      contextual details as the patient moves from the past to the future.

PMID- 22982608
TI  - Expression of the DisA amino acid decarboxylase from Proteus mirabilis inhibits
      motility and class 2 flagellar gene expression in Escherichia coli.
AB  - In Proteus mirabilis, a putative phenylalanine decarboxylase (DisA) acts in a
      regulatory pathway to inhibit class 2 flagellar gene expression and motility. In
      this study, we demonstrate that DisA expression in Escherichia coli blocked
      motility and resulted in a 50-fold decrease in the expression of class 2 (fliA)
      and class 3 (fliC) flagellar genes. However, the expression of flhDC encoding the
      class 1 activator of the flagellar cascade was unchanged by DisA expression at
      both the transcriptional and translational levels. Phenethylamine, a
      decarboxylation product derived from phenylalanine, was able to mimic DisA
      overexpression and decrease both motility and class 2/3 flagellar gene
      expression. In addition, both DisA overexpression and phenethylamine strongly
      inhibited biofilm formation in E. coli. DisA overexpression and exogenous
      phenethylamine could also reduce motility in other enteric bacteria, but had no
      effect on motility in non-enteric Gram-negative bacteria. It is hypothesized that
      phenethylamine or a closely related compound formed by the DisA decarboxylation
      reaction inhibits the formation or activity of the FlhD(4)C(2) complex required
      for activation of class 2 genes.

PMID- 22982609
TI  - The novel peptide PACAP-TAT with enhanced traversing ability attenuates the
      severe lung injury induced by repeated smoke inhalation.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potential
      therapeutic peptide with anti-inflammatory and anti-oxidative effects. In order
      to increase the efficiency of traversing biological barriers, a novel fusion
      peptide PACAP-TAT was produced by tagging PACAP at its C-terminus with 11-amino
      acid TAT protein transduction domain. The results of characteristic assays showed
      that PACAP-TAT activated PACAP specific receptor PAC1 with the same potency as
      PACAP and PACAP-TAT crossed blood-brain barrier (BBB), blood-air barrier (BAB)
      and blood-testis barrier (BTB) with the efficiency about 2.5-fold higher than
      that of PACAP. Both PACAP-TAT and PACAP were used treat the mice with lung injury
      induced by repeated smoke inhalation. It was shown that both PACAP-TAT and PACAP
      decreased the mortality, increased the body weight and inhibited the edema and
      vascular permeability in the lungs of the mice received repeated smoke
      inhalation, while PACAP-TAT displayed more marked effects than PACAP. PACAP-TAT
      decreased myeloperoxidase (MPO) activity, increased catalase (CAT) activity and
      down-regulated interleukin 6 (IL-6) and malondialdehyde (MDA) levels in the lungs
      with a significantly higher efficiency than PACAP. The histopathological analysis
      also showed that PACAP-TAT attenuated the cell filtration and bronchi epithelial
      hyperplasia more significantly than PACAP. Moreover the leukocyte count in blood
      and the serum superoxide dismutase (SOD) activity in the mice treated with PACAP
      TAT were significantly different from that in mice treated with PACAP (p<0.05).
      All these data indicated that PACAP-TAT with increased traversing ability was
      more effective than PACAP in protecting the mice from the lung injury induced by
      repeated smoke inhalation.

PMID- 22982610
TI  - A surfactin cyclopeptide of WH1fungin used as a novel adjuvant for intramuscular
      and subcutaneous immunization in mice.
AB  - WH1fungin, a surfactin cyclopeptide from Bacillus amyloliquefaciens WH1, is
      firstly reported as a novel immunoadjuvant, which can markedly enhance the immune
      response when given in mixture with antigens. After intramuscular or subcutaneous
      immunization, WH1fungin can help to induce both of durable humoral and cellular
      immune response, even as strong as Freund's adjuvant. Both IgG1 and IgG2a antigen
      specific antibodies were elicited from the immunizations indicating a mixed
      Th1/Th2 response. Splenocytes from mice intramuscularly immunized with OVA plus
      WH1fungin responded to OVA CTL peptide stimulation resulting in an increase in
      CD8(+)TNF-alpha(+) and CD8(+)IFN-gamma(+) T cell populations, and also an
      increase in CD4(+)TNF-alpha(+) T cells and CD4(+)IFN-gamma(+) T cell populations
      was found from mice subcutaneously immunized with OVA plus WH1fungin when
      responded to OVA Th peptide stimulation. These results further suggest that
      WH1fungin helps to elicit humoral and cellular responses to OVA. The potential
      mechanism of WH1fungin as an immunoadjuvant was investigated. In vitro assays
      showed that WH1fungin could enter into RAW 264.7 cells, induce ROS accumulation,
      and increase the expression of cell surface markers and cytokines in cells.
      Further investigation suggested that WH1fungin might exert its adjuvant activity
      by ligating with TLR-2 in antigen present cells such as RAW 264.7. Taken
      together, WH1fungin is very potent as a novel adjuvant for development of
      vaccines in the future.

PMID- 22982611
TI  - Hemodynamic actions and mechanisms of systemically administered alpha-MSH analogs
      in mice.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) regulates important
      physiological functions including energy homeostasis and inflammation. Potent
      analogs of alpha-MSH, [Nle(4), D-Phe(7)]-alpha-MSH (NDP-alpha-MSH) and melanotan
      II (MT-II), are widely used in pharmacological studies, but the hemodynamic
      effects associated with their systemic administration have not been thoroughly
      examined. Therefore, we investigated the hemodynamic actions of these compounds
      in anesthetized and conscious C57Bl/6N mice using peripheral routes of
      administration. NDP-alpha-MSH and MT-II induced mild changes in blood pressure
      and heart rate in anesthetized mice compared to the effects observed in conscious
      mice, suggesting that anesthesia distorts the hemodynamic actions of alpha-MSH
      analogs. In conscious mice, NDP-alpha-MSH and MT-II increased blood pressure and
      heart rate in a dose-dependent manner, but the tachycardic effect was more
      prominent than the pressor effect. Pretreatment with the melanocortin (MC) 3/4
      receptor antagonist SHU9119 abolished these hemodynamic effects. Furthermore, the
      blockade of beta(1)-adrenoceptors with metoprolol prevented the pressor effect
      and partly the tachycardic action of alpha-MSH analogs, while the ganglionic
      blocker hexamethonium abrogated completely the difference in heart rate between
      vehicle and alpha-MSH treatments. These findings suggest that the pressor effect
      is primarily caused by augmentation of cardiac sympathetic activity, but the
      tachycardic effect seems to involve withdrawal of vagal tone in addition to
      sympathetic activation. In conclusion, the present results indicate that systemic
      administration of alpha-MSH analogs elevates blood pressure and heart rate via
      activation of MC(3/4) receptor pathways. These effects and the consequent
      increase in cardiac workload should be taken into account when using alpha-MSH
      analogs via peripheral routes of administration.

PMID- 22982612
TI  - Transport of Escherichia coli strains isolated from natural spring water.
AB  - We present a new methodology to scale up bacteria transport experiments carried
      out in the laboratory to practical field situations. The key component of the
      methodology is to characterize bacteria transport not by a constant sticking
      efficiency, but by a range of sticking efficiency values determined from
      laboratory column experiments. In this study, initially, we harvested six
      Escherichia coli strains from springs in Kampala, the capital of Uganda, and then
      we carried out a number of experiments with 1.5m high columns of quartz sand with
      various sampling ports in order to determine the fraction of bacteria as a
      function of sticking efficiency. Furthermore, we developed a simple mathematical
      formulation, based on the steady-state analytical solution for the transport of
      mass in the subsurface, to arrive at bacteria concentrations as a function of
      transport distance. The results of the quartz sand column experiments indicated
      that the fractional bacteria mass and sticking efficiency of most of the strains
      we harvested could be adequately described by a power law. When applying the
      power distributions to the field situation in Kampala, we found that the
      transport distance required to reduce bacteria concentrations with five log units
      ranged from 1.5 to 23m, and this was up to three times more than when using a
      constant sticking efficiency. The methodology we describe is simple, can be
      carried out in a spreadsheet, and in addition to parameters describing transport,
      like pore water flow velocity and dispersion, only two constants are required,
      which define the relation between sticking efficiency and percentage of bacteria
      mass.

PMID- 22982613
TI  - Comments on "More general capillary pressure and relative permeability models
      from fractal geometry" by Kewen Li.

PMID- 22982614
TI  - Wastewater treatment by soil infiltration: Long-term phosphorus removal.
AB  - Phosphorus (P) leaching from on-site wastewater treatment systems may contribute
      to eutrophication. In developed countries the most common on-site treatment
      technique is septic systems with soil infiltration. However, the current
      knowledge about long term P removal in soil treatment systems is not well
      developed and the data used for estimation of P losses from such systems are
      unreliable. In this study we sampled four filter beds from community-scale soil
      treatment systems with an age of between 14 and 22years to determine the long
      term P removal and to investigate the chemical mechanisms behind the observed
      removal. For one site the long-term P removal was calculated using a mass balance
      approach. After analysis of the accumulated P, it was estimated that on average
      12% of the long-term P load had been removed by the bed material. This indicates
      a low overall capacity of soil treatment systems to remove phosphorus. Batch
      experiments and chemical speciation modelling indicated that calcium phosphate
      precipitation was not an important long-term P removal mechanism, with the
      possible exception of one of the sites. More likely, the P removal was induced by
      AlPO(4) precipitation and/or sorption to poorly ordered aluminium compounds, as
      evidenced by strong relationships between oxalate-extractable Al and P.

PMID- 22982615
TI  - Structure and gene cluster of the O-antigen of Escherichia coli O102.
AB  - The O-polysaccharide (O-antigen) of Escherichia coli O102 was studied by sugar
      analysis along with one- and two-dimensional (1)H and (13)C NMR spectroscopy. The
      following structure of the branched pentasaccharide repeating unit was
      established: [formula: see text]. The O-antigen gene cluster of E. coli O102 was
      sequenced. The gene functions were tentatively assigned by comparison with
      sequences in the available databases and found to be in full agreement with the
      E. coli O102 O-polysaccharide structure.

PMID- 22982616
TI  - Role of estrogen receptor beta in gynecological cancer.
AB  - Estrogen receptor beta is expressed in normal and neoplastic ovarian and
      endometrial tissues. Recent studies indicate that levels of this receptor decline
      in ovarian tumorigenesis, like in breast or prostate cancer. Furthermore, ERbeta
      expression has been associated with good prognosis in ovarian cancer. In
      contrast, previous studies on the role of this receptor in endometrial cancer
      suggested that ERbeta might play different roles in the carcinogenesis of the
      ovary and endometrium. Besides its possible role as a prognostic factor, ERbeta
      might be a potential target for the treatment of ovarian and endometrial cancer.

PMID- 22982617
TI  - Reciprocal regulation of HIF-1alpha and 15-LO/15-HETE promotes anti-apoptosis
      process in pulmonary artery smooth muscle cells during hypoxia.
AB  - 15-Hydroxyeicosatetraenoic acid, a predominant metabolic product of arachidonic
      acid (AA) catalyzed by 15-lipoxygenase (15-LO), plays an important role in
      hypoxic pulmonary arterial hypertension (PAH). Hypoxia-inducible factor-1alpha
      (HIF-1alpha) as a critical oxygen-sensitive transcriptional factor participates
      in many physiological and pathological processes including PAH. Therefore, it is
      possible that there may be some connections between HIF-1alpha and 15-LO/15-HETE
      in hypoxic pulmonary artery smooth muscle cells. Our results showed that HIF
      1alpha inhibitor or siRNA reduced hypoxia-induced upregulation of 15-LO and
      endogenous 15-HETE, meanwhile HIF-1alpha expression and transcriptional activity
      were induced by 15-HETE under both normoxic and hypoxic conditions. It suggests
      there exists a potential positive feedback regulatory loop between HIF-1alpha and
      15-LO/15-HETE. Furthermore, cell viability assay and several cell apoptosis
      assays, including TUNEL assay, Western blot, nuclear morphology determination,
      mitochondrial potential analysis, indicated that blocking HIF-1alpha induced
      apoptosis, decreased cell viability and suppressed the anti-apoptosis effects of
      15-HETE. Taken together, our data indicate that upregulation of 15-LO/15-HETE in
      response to hypoxia may be partially mediated by HIF-1alpha which is also
      regulated by 15-HETE in a positive feedback manner, and HIF-1alpha can
      effectively inhibit pulmonary artery smooth muscle cells apoptosis which leads to
      vascular remodeling. The feedback loop between HIF-1alpha and 15-LO/15-HETE would
      obviously reinforce hypoxia-induced anti-apoptosis effect and may become a novel
      target of therapy in PAH.

PMID- 22982618
TI  - The effects of clobazam treatment in rats on the expression of genes and proteins
      encoding glucronosyltransferase 1A/2B (UGT1A/2B) and multidrug resistance
      associated protein-2 (MRP2), and development of thyroid follicular cell
      hypertrophy.
AB  - Clobazam (CLB) is known to increase hepatobiliary thyroxine (T4) clearance in
      Sprague-Dawley (SD) rats, which results in hypothyroidism followed by thyroid
      follicular cell hypertrophy. However, the mechanism of the acceleration of T4
      clearance has not been fully investigated. In the present study, we tried to
      clarify the roles of hepatic UDP-glucronosyltransferase (UGT) isoenzymes (UGT1A
      and UGT2B) and efflux transporter (multidrug resistance-associated protein-2;
      MRP2) in the CLB-induced acceleration of T4-clearance using two mutant rat
      strains, UGT1A-deficient mutant (Gunn) and MRP2-deficient mutant (EHBR) rats,
      especially focusing on thyroid morphology, levels of circulating hormones (T4 and
      triiodothyronine (T3)) and thyroid-stimulating hormone (TSH), and mRNA or protein
      expressions of UGTs (Ugt1a1, Ugt1a6, and Ugt2b1/2) and MRP2 (Mrp). CLB induced
      thyroid morphological changes with increases in TSH in SD and Gunn rats, but not
      in EHBR rats. T4 was slightly decreased in SD and Gunn rats, and T3 was decreased
      in Gunn rats, whereas these hormones were maintained in EHBR rats. Hepatic
      Ugt1a1, Ugt1a6, Ugt2b1/2, and Mrp2 mRNAs were upregulated in SD rats. In Gunn
      rats, UGT1A mRNAs (Ugt1a1/6) and protein levels were quite low, but UGT2B mRNAs
      (Ugt2b1/2) and protein were prominently upregulated. In SD and Gunn rats, MRP2
      mRNA and protein were upregulated to the same degree. These results suggest that
      MRP2 is an important contributor in development of the thyroid cellular
      hypertrophy in CLB-treated rats, and that UGT1A and UGT2B work in concert with
      MRP2 in the presence of MRP2 function to enable the effective elimination of
      thyroid hormones.

PMID- 22982619
TI  - Inhibition of glutathione synthesis eliminates the adaptive response of ascitic
      hepatoma 22 cells to nedaplatin that targets thioredoxin reductase.
AB  - Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer
      mechanism of cisplatin involves TrxR inhibition. We hypothesize that the
      anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second
      generation platinum complex, also targets TrxR. Furthermore, we investigate
      whether the therapeutic efficacy of NDP can be enhanced by simultaneous
      modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis
      inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22)
      cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was
      inhibited by NDP in a dose-dependent manner. A high correlation between the
      inhibition of TrxR activity at 6h and the inhibition of ascitic fluid volume at
      72h was established (r=0.978, p<0.01). As an adaptive response, the viable
      ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype,
      assembled with several-fold more antioxidant enzymes and GSH-predominant non
      protein free thiols. This adaptive response was largely eliminated when BSO was
      co-administered with NDP, leading to the decimation of the H22 cell population
      without enhancing renal toxicity, since at this dose, NDP did not inhibit renal
      TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR
      inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be
      efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on
      ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as
      compared with the single modulation of TrxR using NDP alone.

PMID- 22982620
TI  - Chemopreventive activity of compounds extracted from Casearia sylvestris
      (Salicaceae) Sw against DNA damage induced by particulate matter emitted by
      sugarcane burning near Araraquara, Brazil.
AB  - Ethanolic extract of Casearia sylvestris is thought to be antimutagenic. In this
      study, we attempted to determine whether this extract and casearin X (a clerodane
      diterpene from C. sylvestris) are protective against the harmful effects of
      airborne pollutants from sugarcane burning. To that end, we used the Tradescantia
      micronucleus test in meiotic pollen cells of Tradescantia pallida, the
      micronucleus test in mouse bone marrow cells, and the comet assay in mouse blood
      cells. The mutagenic compound was total suspended particulate (TSP) from air. For
      the Tradescantia micronucleus test, T. pallida cuttings were treated with the
      extract at 0.13, 0.25, or 0.50 mg/ml. Subsequently, TSP was added at 0.3mg/ml,
      and tetrads from the inflorescences were examined for micronuclei. For the
      micronucleus test in mouse bone marrow cells and the comet assay in mouse blood
      cells, Balb/c mice were treated for 15 days with the extract-3.9, 7.5, or 15.0
      mg/kg body weight (BW)-or with casearin X-0.3, 0.25, or 1.2 mg/kg BW-after which
      they received TSP (3.75 mg/kg BW). In T. pallida and mouse bone marrow cells, the
      extract was antimutagenic at all concentrations tested. In mouse blood cells, the
      extract was antigenotoxic at all concentrations, whereas casearin X was not
      antimutagenic but was antigenotoxic at all concentrations. We conclude that C.
      sylvestris ethanolic extract and casearin X protect DNA from damage induced by
      airborne pollutants from sugarcane burning.

PMID- 22982621
TI  - Movement patterns underlying first trial responses in human balance corrections.
AB  - BACKGROUND: We investigated whether the "first trial effect" (FTE) in responses
      to support surface tilt has directional characteristics, or is simply due to a
      startle-like response. The FTE is the difference between the first (unpractised)
      trial response (FTR) and subsequent responses. METHODS: Each group of 10 young
      adults received a series of identical support surface tilts (7.5 degrees , 60
      degrees /s) in one of five leftward tilt directions or pure backward or forward.
      These were followed by randomly selected tilts in at least eight equally spaced
      directions. Only in-place responses were possible as the feet were strapped to
      the support surface. Body kinematics were collected and EMG activity was recorded
      from several trunk, leg and arm muscles. RESULTS: The centre of mass (CoM) vector
      displacement showed a FTE in all tilt directions. It was equally large for all
      directions of backward tilt but smaller for forward and lateral tilts. A similar
      effect was noted for the CoM anterior-posterior FTE. FTRs of lateral CoM
      movements were small for all tilt directions except in the backward left
      direction. A constant amplitude trunk flexion FTE was observed in all tilt
      directions, and pelvis backward motion for backward tilts, preceded by a FTE in
      the abdominal muscles for forward (and lateral) tilts and in the soleus for
      backward (and lateral) tilts. Hip flexion FTEs were largest in backward left
      direction and preceded by increased gluteus medius and deltoid FTR activity. FTRs
      in sternocleidomastoideus muscles, generally associated with startle activity,
      were largest in lateral and forward tilt directions. CONCLUSIONS: FTRs appear to
      consist of either a forward, backward or lateral movement strategy each imposed
      on an adapted response strategy. Only the lateral response shows a strong
      directional sensitivity. We hypothesise that FTR amplitudes result from a failure
      of the CNS to weight properly the stimulus metrics present in lower leg
      proprioceptive and vestibular inputs.

PMID- 22982622
TI  - Short-term retrospective versus prospective memory processing as emergent
      properties of the mind and brain: human fMRI evidence.
AB  - The functional-neuroanatomical substrates for short-term retrospective versus
      prospective memory processing were examined in a delay task, in which associative
      choices were made conditionally based on the presenting discriminative/cue
      stimulus. Delay-period prospection could be of the intended choice and/or the
      expected response outcome, whereas delay-period retrospection would be of the
      just-presented cue stimulus. Previous results have shown that the spontaneous
      process of unique outcome prospection did not implicate the lateral prefrontal
      cortex (PFC) but instead implicated the lateral posterior parietal cortex (LPPC)
      in a modality-independent fashion (Mok et al., 2009). Spontaneous retrospection
      was more dependent on the medial temporal lobe (MTL). Nevertheless, it was
      anticipated that the more explicit process of prospecting an intended choice
      would implicate the lateral PFC. To verify this, Mok et al.'s data were further
      analyzed, with new control data. Healthy, young adults performed delayed
      discriminative choices under procedures that biased them toward different degrees
      of delay-period prospection: higher-using cue-unique, differential outcomes (DO);
      versus lower-using a non-unique, common outcome (CO), or unpredictable, non
      differential outcomes (NDO). Experimental participants performed the DO versus CO
      procedures concurrently, while undergoing event-related functional magnetic
      resonance imaging (fMRI). Separately, control participants provided data for: the
      NDO condition; related comparison tasks, which biased them toward different
      degrees of delay-period retrospection; and null-event trials. Expectedly, the
      more explicit process of prospecting an intended associative choice implicated
      the lateral PFC, as part of and together with other components of the multiple
      demand network. Comparisons against null-event trials indicated that the
      sustained delay activity observed in MTL and LPPC, respectively, was part of
      default brain activity. These results demonstrated that short-term retrospection
      and prospection may emerge without necessarily relying on working memory-specific
      brain networks. Furthermore, attention may not necessarily be recruited to
      realize working memory. When cognitive processes are spontaneously experienced,
      they may be facilitated by the default brain network.

PMID- 22982623
TI  - Expression of the core exon-junction complex factor eukaryotic initiation factor
      4A3 is increased during spatial exploration and striatally-mediated learning.
AB  - Regulation of dendritically localized mRNAs offers an important means by which
      neurons can sculpt precise signals at synapses. Arc is one such dendritically
      localized mRNA, and it has been shown to contain two exon-junction complexes
      (EJCs) within its 3'UTR. The EJC has been postulated to regulate cytoplasmic Arc
      mRNA availability through translation-dependent decay and thus contribute to
      synaptic plasticity. Core proteins of the EJC include eIF4A3, an RNA helicase,
      and Magoh, which stabilizes the interaction of eIF4A3 with target mRNAs. Arc mRNA
      expression is activity-regulated in numerous brain regions, including the dorsal
      striatum and hippocampus. Therefore in this study, the in vivo expression of
      these core EJC components was investigated in adult Sprague-Dawley rats to
      determine whether there are also behaviorally regulated changes in their
      expression. In the present work, there was no change in the expression of Magoh
      mRNA following spatial exploration, a paradigm previously reported to robustly
      and reliably upregulate Arc mRNA expression. Interestingly, however, there were
      increases in eIF4A3 mRNA levels in the dorsal striatum and hippocampus following
      spatial exploration, similar to previous reports for Arc mRNA. Furthermore, there
      were activity-dependent changes in eIF4A3 protein distribution and expression
      within the striatum following spatial exploration. Importantly, eIF4A3 protein
      colocalized with Arc mRNA in vivo. Like Arc mRNA expression, eIF4A3 mRNA
      expression in the dorsomedial striatum, but not dorsolateral striatum or
      hippocampus, significantly correlated with behavioral performance on a striatally
      mediated, response-reversal learning task. This study provides direct evidence
      that a core EJC component, eIF4A3, shows activity-dependent changes in both mRNA
      and protein expression in the adult mammalian brain. These findings thus further
      implicate eIF4A3 as a key mediator of Arc mRNA availability underlying learning
      and memory processes in vivo.

PMID- 22982624
TI  - Long-term exercise treatment reduces oxidative stress in the hippocampus of aging
      rats.
AB  - Exercise can exert beneficial effects on cognitive functions of older subjects
      and it can also play an important role in the prevention of neurodegenerative
      diseases. At the same time it is perceivable that limited information is
      available on the nature of molecular pathways supporting the antioxidant effects
      of exercise in the brain. In this study 12-month old, middle-aged female Wistar
      rats were subjected to daily moderate intensity exercise on a rodent treadmill
      for a period of 15weeks which covered the early aging period unmasking already
      some aging-related molecular disturbances. The levels of reactive oxygen species
      (ROS), the amount of protein carbonyls, the levels of antioxidant intracellular
      enzymes superoxide dismutases (SOD-1, SOD-2) and glutathione peroxidase (GPx)
      were determined in the hippocampus. In addition, to identify the molecular
      pathways that may be involved in ROS metabolism and mitochondrial biogenesis, the
      activation of 5'-AMP-activated protein kinase (AMPK), the protein level of
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription
      factor A (mtTFA) were measured. Our results revealed a lower level of ROS
      associated with a reduced amount of protein carbonyls in the hippocampus of
      physically trained rats compared to sedentary controls. Furthermore, exercise
      induced an up-regulation of SOD-1 and GPx enzymes, p-AMPK and PGC-1alpha, that
      can be related to an improved redox balance in the hippocampus. These results
      suggest that long-term physical exercise can comprises antioxidant properties and
      by this way protect neurons against oxidative stress at the early stage of aging.

PMID- 22982625
TI  - Upregulation of calcium binding protein, S100A6, in activated astrocytes is
      linked to glutamate toxicity.
AB  - S100A6 (calcyclin), an EF-hand calcium binding protein, is considered to exert
      various functions, e.g., cell proliferation and differentiation, calcium
      homeostasis, and neuronal degeneration. In this study, we aimed to investigate
      whether S100A6 might be linked to glutamate toxicity using three animal models
      and pharmacological interventions. We first examined the age-related changes in
      S100A6 immunoreactivity in the mouse hippocampus, considering that an important
      negative aspect of brain aging is linked to increased extracellular glutamate.
      The surface area of S100A6-positive (+) astrocytes was significantly larger in
      aged mice than in young mice, while the numbers of S100beta+ astrocytes did not
      change with age. In the second experiment, we examined the alterations in S100A6
      immunoreactivity in the injured hypoglossal nucleus, because glutamate toxicity
      is considered to contribute to neuronal death after axotomy. There was no
      apparent S100A6 immunoreactivity in the hypoglossal nucleus of sham control
      animals. However, intense labeling for S100A6 in activated astrocytes was
      observed in the axotomized hypoglossal nucleus of mice. Administration of
      ceftriaxone, an astrocyte glutamate transporter enhancer, to axotomized mice
      significantly decreased the immunoreactivity for S100A6. In the third experiment,
      we tested an animal model of epilepsy using kainic acid (KA), a glutamate analog.
      In the mouse hippocampus after KA injection, S100A6 immunoreactivity was
      significantly increased in astrocytes, and pyknotic changes were observed in CA3
      pyramidal neurons. Treatment of MK-801, an N-methyl-d-aspartate receptor
      antagonist, counteracted the KA-induced increase in S100A6 immunoreactivity, and
      reduced the numbers of pyknotic neurons. Our results indicate that upregulation
      of astrocytic S100A6 in response to extracellular glutamate may be involved in
      neuronal damage under pathophysiological conditions.

PMID- 22982626
TI  - Effects of sex and chronic neonatal nicotine treatment on Na2+/K+/Cl- co
      transporter 1, K+/Cl- co-transporter 2, brain-derived neurotrophic factor, NMDA
      receptor subunit 2A and NMDA receptor subunit 2B mRNA expression in the postnatal
      rat hippocampus.
AB  - Chronic exposure to nicotine during the first postnatal week in rats, a
      developmental period that corresponds to the third trimester of human gestation,
      results in sexually dimorphic long-term functional defects in the adult
      hippocampus. One potential cause could be the sex-specific differences in the
      maturation of GABA(A) receptor-mediated responses from excitatory to inhibitory,
      which depends on the expression of the Na(2+)/K(+)/Cl(-) co-transporter 1 (NKCC1)
      and the K(+)/Cl(-) co-transporter 2 (KCC2). In the rat hippocampus, this switch
      occurs during the first and second postnatal week in females and males,
      respectively, and is regulated by nicotinic receptor activation. Excitatory
      GABAergic signaling can increase brain-derived neurotrophic factor (BDNF)
      expression, which might exacerbate sex differences by impacting synaptogenesis.
      We hypothesized that chronic neonatal nicotine (CNN) exposure differentially
      regulates the expression of these co-transporters and BDNF in males and females.
      We use quantitative isotopic in situ hybridization to examine the expression of
      mRNAs for NKCC1, KCC2, BDNF, and NMDA receptor subunit 2A (NR2A) and NMDA
      receptor subunit 2B (NR2B) in the postnatal day (P) 5 and 8 rat hippocampi in
      both sexes that were either control-treated or with 6mg/kg/day nicotine in milk
      formula (CNN) via gastric intubation starting at P1. In line with prolonged
      GABAergic excitation, we found that at P5 males had significantly higher mRNA
      expression of NKCC1 and BDNF than females. CNN treatment resulted in a
      significant increase in KCC2 and BDNF mRNA expression in male but not female
      hippocampus (p<0.05). Males also had higher expression of NR2A and lower
      expression of NR2B at P5 compared to females (p<0.05). At P8, there were neither
      sex nor treatment effects on mRNA expression, indicating the end of a critical
      period for sensitivity to nicotine. These results suggest that differential
      maturation of GABA(A)R-mediated responses result in sex-specific sensitivity to
      nicotine during early postnatal development, potentially explaining the
      differential long-term effects of CNN on hippocampal function.

PMID- 22982627
TI  - Histone deacetylation mediates the rejuvenation of osteoblastogenesis by the
      combination of 25(OH)D3 and parathyroid hormone in MSCs from elders.
AB  - Vitamin D metabolites are important effectors of bone and mineral homeostasis.
      Human bone marrow stromal cells (hMSCs) are targets of 1alpha,25-dihydroxyvitamin
      D [1alpha,25(OH)2D] action to promote their differentiation to osteoblasts.
      Osteoblastogenesis is also stimulated by 25-hydroxyvitamin D [25(OH)D], an effect
      that requires conversion to 1alpha,25(OH)2D3 by 25-hydroxyvitamin D3 1alpha
      hydroxylase (CYP27B1). These findings support an autocrine/paracrine role of
      vitamin D metabolism in osteoblastogenesis of hMSCs. In this study, we assessed
      whether and by what mechanisms osteoblastogenesis could be rejuvenated with hMSCs
      from elders. First, knockdown studies with VDR-siRNA showed that both the pro
      differentiation and anti-proliferative effects of 1alpha,25(OH)2D3 required VDR.
      Second, 100nM 25(OH)D3 (p<0.01 vs. control, ANOVA) and 100nM PTH1-34 (p<0.05)
      significantly stimulated alkaline phosphatase (ALP) activity (a measure of
      osteoblastogenesis), with a synergistic effect when combined (p<0.001).
      Scriptaid, an inhibitor of histone deacetylase, blocked the effect of 25(OH)D3
      and PTH on osteoblastogenesis. Scriptaid alone downregulated VDR in hMSCs. These
      data demonstrate that histone deacetylation is required for the synergistic
      effect of 25(OH)D3 and PTH on osteoblastogenesis in hMSCs. Both VDR siRNA and
      Scriptaid dowregulated VDR mRNA and inhibited osteoblastogenesis. Thus,
      epigenetic regulation of the VDR may be central to rejuvenating
      osteoblastogenesis in hMSCs from elders. This article is part of a Special Issue
      entitled 'Vitamin D Workshop'.

PMID- 22982628
TI  - Prevention of preneoplastic lesions by dietary vitamin D in a mouse model of
      colorectal carcinogenesis.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer morbidity and
      mortality in Western countries. One of the risk factors for colorectal
      tumorigenesis is vitamin D insufficiency. The aim of this study was to establish
      whether increasing dietary vitamin D intake can prevent or delay development of
      chemically induced preneoplastic lesions in the colon of mice. We fed six weeks
      old female C57BL/6J mice (n=28) with increasing vitamin D3 concentrations (100,
      400, 1000, 2500, 5000IU/kg diet). To induce dysplasia, a preneoplastic lesion, we
      injected mice with the carcinogen azoxymethane (10mg/kg) intraperitoneally,
      followed by three cycles of 2% dextran sodium sulfate salt, a tumor promoter, in
      the drinking water. To test our hypothesis that high vitamin D intake prevents
      formation of preneoplastic lesions, we have investigated the effect of increasing
      dietary vitamin D on development of premalignant colorectal lesions, serum 25
      hydroxyvitamin D3 (25-D3) levels, and expression of renal vitamin D system genes.
      Dietary vitamin D concentration correlated inversely with dysplasia score
      (Spearman's correlation coefficient, rho: -0.579, p=0.002) and positively with
      serum 25-D3 levels (rho: 0.752, p=0.001). Increasing dietary vitamin D
      concentration beyond 1000IU/kg led to no further increase in circulating 25-D3
      levels, while the dysplasia score leveled out at >=2500IU/kg vitamin D. High
      dietary vitamin D intake led to increased renal mRNA expression of the vitamin D
      catabolizing enzyme cyp24a1 (rho: 0.518, p=0.005) and decreased expression of the
      vitamin D activating enzyme cyp27b1 (rho: -0.452, p=0.016), protecting the body
      from toxic serum levels of the active vitamin D metabolite 1,25-dihydroxyvitamin
      D3 (1,25-D3). Our data showed that increasing dietary vitamin D intake is able to
      prevent chemically induced preneoplastic lesions. The maximum impact was achieved
      when the mice consumed more than 2500IU vitamin D/kg diet. This article is part
      of a Special Issue entitled 'Vitamin D Workshop'.

PMID- 22982630
TI  - Isolation of rat adrenocortical mitochondria.
AB  - This report describes a relatively simple and reliable method for isolating
      adrenocortical mitochondria from rats in good, reasonably pure yield. These
      organelles, which heretofore have been unobtainable in isolated form from small
      laboratory animals, are now readily accessible. A high degree of mitochondrial
      purity is shown by the electron micrographs, as well as the structural integrity
      of each mitochondrion. That these organelles have retained their functional
      integrity is shown by their high respiratory control ratios. In general, the
      biochemical performance of these adrenal cortical mitochondria closely mirrors
      that of typical hepatic or cardiac mitochondria.

PMID- 22982629
TI  - 1,25(OH)(2)vitamin D(3) enhances myogenic differentiation by modulating the
      expression of key angiogenic growth factors and angiogenic inhibitors in
      C(2)C(12) skeletal muscle cells.
AB  - Vitamin D is mostly recognized for its regulation of calcium homeostasis in
      relation to the intestine, kidney, and bone. Although clinical studies have
      linked vitamin D with increased muscle function and strength, little is known of
      its underlying molecular mechanism. We recently demonstrated that 1,25-D3 exerts
      a direct pro-myogenic effect on skeletal muscle cells; this has provoked our
      investigation of 1,25-D's effect on angiogenesis, a vital process for new
      capillary development and tissue repair. In this study, we examined the mechanism
      by which 1,25-D3 modulates key angiogenic growth factors and angiogenic
      inhibitors. C(2)C(12) myoblasts were incubated with 100 nM 1,25-D3 or placebo for
      1, 4 and 10 days. At the end of the respective incubation time, total RNA was
      isolated for PCR arrays and for qRT-PCR. Total proteins were isolated for Western
      blots and proteome profiler arrays. The addition of 1,25-D3 to C(2)C(12)
      myoblasts increased VEGFa and FGF-1: two pro-angiogenic growth factors that
      promote neo-vascularization and tissue regeneration, and decreased FGF-2 and TIMP
      3: two myogenic and/or angiogenic inhibitors. Our previous study demonstrated
      that 1,25-D3 altered IGF-I/II expression, consistent with the observed changes in
      VEGFa and FGF-2 expression. These results extend our previous findings and
      demonstrate the modulation of angiogenesis which may be an additional mechanism
      by which 1,25-D3 promotes myogenesis. This study supports the mechanistic
      rationale for assessing the administration of vitamin D and/or vitamin D analogs
      to treat select muscle disorders and may also provide an alternative solution for
      therapies that directly manipulate VEGF and FGF's to promote angiogenesis.

PMID- 22982631
TI  - Fetal progenitor cell transplantation treats methylmalonic aciduria in a mouse
      model.
AB  - Methylmalonic aciduria is a rare disorder caused by an inborn error of organic
      acid metabolism. Current treatment options are limited and generally focus on
      disease management. We aimed to investigate the use of fetal progenitor cells to
      treat this disorder using a mouse model with an intermediate form of
      methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at
      embryonic day 15-17 and intravenously transplanted into sub-lethally irradiated
      mice. Liver donor cell engraftment was determined by PCR. Disease correction was
      monitored by urine and blood methylmalonic acid concentration and weight change.
      Initial studies indicated that pre-transplantation sub-lethal irradiation
      followed by transplantation with 5 million cells were suitable. We found that a
      double dose of 5 million cells (1 week apart) provided a more effective
      treatment. Donor cell liver engraftment of up to 5% was measured. Disease
      correction, as defined by a decrease in blood methylmalonic acid concentration,
      was effected in methylmalonic acid mice transplanted with a double dose of cells
      and who showed donor cell liver engraftment. Mean plasma methylmalonic acid
      concentration decreased from 810 +/- 156 (sham transplanted) to 338 +/- 157
      MUmol/L (double dose of 5 million cells) while mean blood C3 carnitine
      concentration decreased from 20.5 +/- 4 (sham transplanted) to 5.3 +/- 1.9
      MUmol/L (double dose of 5 million cells). In conclusion, higher levels of
      engraftment may be required for greater disease correction; however these studies
      show promising results for cell transplantation biochemical correction of a
      metabolic disorder.

PMID- 22982632
TI  - Survey of Paramecium duboscqui using three markers and assessment of the
      molecular variability in the genus Paramecium.
AB  - The genus Paramecium (phylum Ciliophora) is one of the best-known among protozoa.
      Nevertheless, the knowledge on the diversity and distribution of species within
      this genus was remarkably scarce until recent times. In the last years a
      constantly growing amount of data has formed, especially on the distribution of
      species and the characterization of molecular markers. Much effort has been made
      on detecting clades inside each morphospecies, which could suggest the presence
      of sibling species complexes as in the famous case of Paramecium aurelia. In this
      work we present new data on Paramecium duboscqui, one of the morphospecies that
      have not yet been surveyed employing DNA sequences as markers. We obtained data
      from nine strains sampled around the world, using the three most commonly
      employed markers (18S rRNA gene, ITS1-5.8S-ITS2 and COI gene sequences).
      Moreover, we compared our results with those already available for other
      Paramecium species, and performed phylogenetic analyses for the entire genus. We
      also expanded the knowledge on the ITS2 secondary structure and its usefulness in
      studies on Paramecium. Our approach, that considers the data of all the species
      together, highlighted some characteristic patterns as well as some ambiguities
      that should be further investigated.

PMID- 22982633
TI  - Phylogeny of bent-toed geckos (Cyrtodactylus) reveals a west to east pattern of
      diversification.
AB  - The Asian/Pacific genus Cyrtodactylus is the most diverse and among the most
      widely distributed genera of geckos, and more species are continually being
      discovered. Major patterns in the evolutionary history of Cyrtodactylus have
      remained largely unknown because no published study has broadly sampled across
      the geographic range and morphological diversity of the genus. We assembled a
      data set including sequences from one mitochondrial and three nuclear loci for 68
      Cyrtodactylus and 20 other gekkotan species to infer phylogenetic relationships
      within the genus and identify major biogeographic patterns. Our results indicate
      that Cyrtodactylus is monophyletic, but only if the Indian/Sri Lankan species
      sometimes recognized as Geckoella are included. Basal divergences divide
      Cyrtodactylus into three well-supported groups: the single species C. tibetanus,
      a clade of Myanmar/southern Himalayan species, and a large clade including all
      other Cyrtodactylus plus Geckoella. Within the largest major clade are several
      well-supported subclades, with separate subclades being most diverse in Thailand,
      Eastern Indochina, the Sunda region, the Papuan region, and the Philippines,
      respectively. The phylogenetic results, along with molecular clock and ancestral
      area analyses, show Cyrtodactylus to have originated in the circum-Himalayan
      region just after the Cretaceous/Paleogene boundary, with a generally west to
      east pattern of colonization and diversification progressing through the
      Cenozoic. Wallacean species are derived from within a Sundaland radiation, the
      Philippines were colonized from Borneo, and Australia was colonized twice, once
      via New Guinea and once via the Lesser Sundas. Overall, these results are
      consistent with past suggestions of a Palearctic origin for Cyrtodactylus, and
      highlight the key role of geography in diversification of the genus.

PMID- 22982634
TI  - Hormonal imprinting in the unicellular Tetrahymena: the proto-model of
      epigenetics.
AB  - The unicellular ciliate, Tetrahymena has a complete hormonal system. It has
      receptors for receiving hormones, produces, stores and secretes hormones, similar
      to mammalian ones and has signal transduction pathways, for transmitting the
      information given by the hormones. The first encounter with a hormone provokes
      the hormonal imprinting under the effect of which the further encounters with the
      same hormone induces altered (usually enhanced) reaction (hormone binding,
      hormone synthesis, chemoattraction, movement, growth etc.). The effect of
      imprinting is durable, it can be observed also after 1000 generations, or after
      one year in non-dividing cells. Receptors of the nuclear envelope also can be
      imprinted. The plasma membrane receptors provoked by imprinting are similar to
      the receptors of mammals. Although steroid hormones are not present in
      Tetrahymena, the production of them and their receptors can be induced by
      imprinting. The hormonal imprinting is an epigenetic process and inhibition of
      DNA-methylation alters the imprinting. Hormonal imprinting in Tetrahymena was
      likely the first epigenetic phenomenon which was justified at cellular level. It
      is very useful for the unicells, as it helps to avoid dangerous molecules more
      easily or to find useful ones and by this contributes to the permanence of the
      population's life.

PMID- 22982635
TI  - Seed mycoflora of Ephedra aphylla and amino acid profile of seed-borne
      Aspergillus flavus.
AB  - Twenty-seven seed samples of Ephedra aphylla were collected from different
      rangelands in Riyadh region, Saudi Arabia during seed production season of 2010.
      They were assessed to determine the incidence of seedborne fungal flora using
      both agar plate and blotter paper methods. The investigation of the seeds yielded
      thirty four fungal species belonging to twelve genera, which are new record to
      seed-brone mycoflora of E. aphylla in Saudi Arabia. The agar plate method was
      found superior over blotter methods. The genus Aspergillus was the most prevalent
      one followed by Fusarium, Penicillium, Alternaria, and Chaetomium. Only eighteen
      isolates of A. flavus (~ 28.6% of total isolates) were able to produce
      aflatoxins. Mycelial amino acids profile of selected aflatoxigenic isolates of A.
      flavus was investigated and five amino acids, namely cystein, lysine, praline,
      tryptophan and valine were common in mycelia and all of them were aflatoxins
      producers. Based on the dissimilarity coefficient between the isolates and their
      amino acids patterns, high diversity among the population of A. flavus has been
      recorded.

PMID- 22982636
TI  - Improvement of tea leaves fermentation through pectinases.
AB  - The pectinase enzymes isolated from Aspergillus niger, Byssochlamys fulva and
      Mucor circinelloides were used for fermentation of tea leaves from Camellia
      sinensis plant. The use of partially purified enzymes from Aspergillus niger and
      Mucor circinelloides resulted in significant (p < 0.001) increase in the phenolic
      compounds, hence, improvement in tea quality. Maximum increase in phenolic
      compounds was found in tea leaves treated with partially purified
      polygalacturonase (PGase) from Mucor circinelloides. Hence, purified
      polygalacturonase from Mucor circinelloides was used to study its effect on the
      improvement of tea leaves fermentation. The partially purified polygalacturonase
      from Mucor circinelloides was found to be most effective in tea fermentation,
      whereas pectin lyase from Byssochlamys fulva had little role in improvement of
      tea quality.

PMID- 22982637
TI  - Debilitating progressive encephalitis in a patient with BTK deficiency.
AB  - X-linked agammaglobulinemia (XLA), also known as Bruton's tyrosine kinase (BTK)
      deficiency, is a primary antibody deficiency, characterized by low number of B
      cells, agammaglobulinemia and increased susceptibility to a variety of
      infections. Herein, we report a case of XLA with confirmed BTK mutation that
      developed neurological deficits. While we could not detect any responsible
      microorganism in spite of comprehensive workup, brain magnetic resonance imaging
      revealed moderate brain atrophy. The diagnosis of progressive encephalitis was
      made for this patient. Patients with XLA have a higher chance of encephalitis
      compared with other primary antibody deficiencies. Given the violent nature of
      encephalitis, it is a concern among XLA patients.

PMID- 22982638
TI  - Autoimmune diseases detected in children with primary immunodeficiency diseases:
      results from a reference centre at middle anatolia.
AB  - Primary immunodeficiency diseases (PIDs) are a heterogeneous group of disorders
      that genetically affect distinct components of the immune system; thus,
      predispose individuals to recurrent infections, allergy, autoimmunity, and
      malignancies. In this retrospective study, autoimmune diseases (ADs), which
      developed during the course of PID in children, were discussed.Twenty-five
      patients were included in this study. Symptoms related to ADs, such as autoimmune
      thyroiditis, type 1 diabetes mellitus, coeliac disease, juvenile idiopathic
      arthritis, dermatomyositis, autoimmune haemolytic anaemia, leukocytoclastic
      vasculitis, Henoch-Schonlein purpura, hypoparathyroidism, alopecia areata,
      Addison's disease, vitiligo and systemic lupus erythematosus were detected in
      these patients, who have been followed with diagnosis of PID including common
      variable immunodeficiency, selective and partial IgA deficiency, Wiskott-Aldrich
      syndrome, ataxia telangiectasia, hyperimmunoglobulin E syndrome, chronic
      mucocutaneous candidiasis, Griscelli syndrome, and partial C4
      deficiency.Immunodeficiency and autoimmune phenomenon may concomitantly present
      in an individual, although they seem to be incompatible ends in the spectrum of
      the clinical immune response. Patients with primary immune deficiency should be
      closely monitored for development of autoimmune diseases.

PMID- 22982639
TI  - Hospital acquired pneumonia: comparison of culture and real-time PCR assays for
      detection of Legionella pneumophila from respiratory specimens at Tehran
      hospitals.
AB  - Legionella pneumophila is an important etiological agent in both hospital and
      community acquired pneumonia. The sensitivity of culture for isolation of L.
      pneumophila from clinical specimens is low and time consuming. Similar problem
      also exists when the method of direct immunofluorescence is used. To detect this
      organism quantitatively from respiratory specimens, a Taq Man based real-time PCR
      targeting the mip sequence was developed. Both real-time PCR and culture methods
      were applied on 262 respiratory specimens from 262 ICU patients with pneumonia
      admitted to 5 different hospitals in Tehran. The results of real-time PCR were
      compared with those obtained by culture. Real-time PCR and culture found 12 and 4
      specimens, respectively, as positive for L. pneumophila. Its technical
      specificity (100%) was checked against a panel of microorganisms consisting of
      both Gram-positive and Gram-negative bacteria. Our real-time PCR assay showed
      high sensitivity (100%) and specificity (96.9%) and could detect 200 organisms
      per ml from respiratory specimens. Using real-time PCR as a screening method, the
      frequency of nosocomial pneumonia with L. pneumophila at Tehran hospitals was
      estimated as 4.58%.

PMID- 22982640
TI  - Incidence of diarrhoeagenic Escherichia coli isolated from young children with
      diarrhoea in the west of Iran.
AB  - Diarrhoeagenic Escherichia coli (DEC) represents a main group of enteric
      pathogens that cause human diarrhoea. Because it is not simply distinguished from
      normal flora by simple laboratory methods, modern molecular diagnostic assays are
      necessary. Although it is neither necessary nor applicable to perform PCR for all
      patients, it is of many advantages to verify the prevalence of DEC in different
      areas by this method. Knowing the prevalence of DEC in an area, we can focus on
      few pathogens and narrow our antimicrobial treatment. The aim of this study is to
      evaluate the contribution of the different DEC categories in children diarrhoea
      in the west of Iran.The stool specimens of 251 children with diarrhoea were
      collected from June to September 2007. Polymerase chain reaction (PCR) was
      performed to determine the presence of enteropathogenic (EPEC), enterotoxigenic
      (ETEC), entero-invasive (EIEC), Shiga toxin-producing (STEC) and entero
      aggregative (EAEC) strains. ETEC strains were isolated from 13 and EAEC strains
      from 16 children. STEC was detected in 7 children, and no EIEC was isolated.
      Finally, EPEC strains were isolated in 41 cases. EAEC and EPEC are the most
      frequent DECs in children less than 10 years of age in West of Iran.

PMID- 22982641
TI  - The most common isolates from pleural infections.
AB  - Isolation and identification of the pathogens are important for appropriate
      treatment of pleural infections. Distribution of the most frequent causative
      agents varies throughout the world and may change in time.The objective of the
      study is to analyze the bacteriological isolates of pleural fluids in order to
      identify the most frequent infectious agents and assess their variability in
      time.The retrospective study included 272 patients with positive pleural fluid
      samples analyzed in 5-year period. The samples were examined using the
      conventional microbiological technique.Of 315 bacterial isolates the most common
      were streptococcal species, 105 (33%), of which 55 (17.3%) represented the
      Streptococcus milleri group. Gram-positive anaerobic cocci were detected in 56
      (17.6%) isolates. Enterobacteriaceae family included 27 (8.5%) isolates and
      Pseudomonas aeruginosa was registered in 13 (4.1%). No statistically significant
      difference was registered in pathogen distribution in the examined period (p =
      0.288).The most common agents of community-acquired pleural infections are the
      Streptococcus milleri group and anaerobic Gram-positive cocci. They differ from
      the most common pathogens of pneumonia. Among the hospital-acquired pleural
      infections, Pseudomonas species, Staphylococcus aureus and enterobacteria
      prevail. The distribution of bacterial agents isolated in the 5-year period
      exhibits no significant differences.

PMID- 22982642
TI  - Suppression of ConA-induced inflammatory ascites by lipopolysaccharide (LPS) in
      mice.
AB  - The effect of pre-treatment with Escherichia coli O83 lipopolysaccharide (LPS) on
      concanavalin A-induced ascites was examined. The LPS was injected
      intraperitoneally (i.p.) in different doses to mice, and then ascites was induced
      by i.p. administration of concanavalin A (ConA) (25 mg/kg b.w.). After 2.5 h the
      mice were killed and the ascitic fluid was collected and measured. The LPS
      produced a marked and dose-dependent inhibition of ConA-induced ascites and the
      effect of pre-treatment lasted up to almost a week. Complete inhibition could not
      be achieved. If administered alone, LPS did not produce ascites.It is well known
      that LPS enhances vascular permeability in several tissues, but the present work
      shows that peritoneal permeability is not enhanced by this agent. Suppression of
      ConA-induces ascites may be explained by the hypotonic effect of LPS.

PMID- 22982643
TI  - Genetic and phylogenetic analysis of avian extraintestinal and intestinal
      Escherichia coli.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) isolates of animals and man
      are known to carry specific virulence associated genes. The intestinal tract, it
      is primarily colonized by various strains of commensal E. coli but it may include
      ExPEC as well. Here we aimed to assess possible genetic and evolutionary linkages
      between extraintestinal pathogenic and intestinal (commensal) E. coli of poultry.
      For that purpose we analysed 71 ExPEC isolates, and 40 intestinal isolates
      assumed to be commensal E. coli (IntEC), from dead chickens and turkey poults for
      26 virulence related genes. Although the two groups shared several virulence
      determinants the genes pic, papC, and cdtIV were exclusively present in ExPEC and
      further five genes (colV, iss, kpsM, tsh and iutA), were significantly more
      frequent among ExPEC. Phylogenetic backgrounds of ExPEC and of IntEC isolates
      indicated significant differences. A 40% of ExPEC belonged to phylogroup A
      primarily containing strains of serogroup O78. Phylogroup D contained ExPEC
      strains of serogroups O53 (2 strains) and O115 (5 strains) characterized by the
      cdt-IV genes, suggesting the existence of new clones of avian ExPEC in
      phylogenetic group D. On the other hand, a 42.5% of IntEC belonged to phylogroup
      B1 with diverse serogroups. Our data provide insight into the clonal evolution of
      avian ExPEC especially in phylogenetic groups A and D, resulting avian ExPEC with
      similarities to human ExPEC.

PMID- 22982644
TI  - Novel NSP4 genotype in a camel G10P[15] rotavirus strain.
AB  - In this study a Kuwaiti camel rotavirus strain, RVA/Camel
      wt/KUW/s21/2010/G10P[15], is characterized by sequencing and phylogenetic
      analysis. The strain had multiple genes with high nucleotide sequence
      similarities to ovine and bovine strains (VP2, <= 96%; NSP2 and NSP5, <= 97%,
      NSP3, <= 94%), or, to porcine strains (VP1, <= 89%). Other genes had moderate
      sequence similarities (VP4, <= 87%; VP6, <= 81%; VP7, <= 82%) with reference
      strains from ruminants. The NSP4 gene shared limited sequence identity (<= 71%)
      with other mammalian and avian rotavirus NSP4 types, and was designated a novel
      genotype, E15. This study demonstrates genetic diversity in the outer capsid and
      some backbone genes of an old-world camelid rotavirus strain and uncovers its
      common evolutionary roots with strains from other ruminants.

PMID- 22982645
TI  - Changes in the serotypes of Hungarian pneumococci isolated mainly from invasive
      infections: a review of all available data between 1988 and 2011.
AB  - Streptococcus pneumoniae is responsible for a high level of morbidity and
      mortality, especially among children. For a long time, only the polysaccharide
      vaccine was available against pneumococcal infections, but in the last decade
      special conjugate vaccines were developed for paediatric use. These vaccines have
      made a deep impact on serotype distribution all over the world, by suppressing
      those serotypes included in the vaccines, while new, previously rare types
      emerged. These changes have been monitored closely in numerous publications all
      over the world. Nevertheless, data on pneumococcal serotypes in Hungary were
      mostly published in Hungarian, therefore not available in the international
      literature. In this meta-analysis, our aim was to collect and summarise all
      available data, and try to follow the changes observed after the introduction of
      the conjugate vaccines.

PMID- 22982646
TI  - A framework for modeling ocular drug transport and flow through the eye using
      micro-CT.
AB  - This study uses micro-computed tomography (micro-CT) imaging for assessment of
      concentration and transport mechanisms of ocular drug surrogates following
      intravitreal injection. Injections of an iodinated contrast agent were
      administered to enucleated porcine eyes prior to scanning over 192 min. Image
      analysis was performed using signal profiles and regions of interest that
      corresponded to specific iodine concentrations. Diffusion coefficients of the
      injected iodine solutions were calculated using nonlinear regression analysis
      with a diffusion model. There was a predominantly diffusive component in the
      movement of the contrast to the back of the eye in the horizontal (sagittal &
      coronal) directions, with ultimate retinal fate observed after 120 min. The
      diffusion coefficients were found to have a mean of 4.87 * 10(-4) mm(2) s(-1) and
      standard deviation of 8.39 * 10(-5) mm(2) s(-1) for 150 mg ml(-1) iodine
      concentration and 6.13 * 10(-4) +/- 1.83 * 10(-4) mm(2) s(-1) for 37.5 mg ml(-1)
      concentration. However, it should be noted that these coefficients were time
      dependent and were found to decay as the diffusion front interacted with the
      retinal wall. A real-time, accurate, non-invasive method of tracking a bolus and
      its concentration is achieved using a high spatial resolution and fast scanning
      speed micro-CT system.

PMID- 22982647
TI  - Beyond the usual suspects.

PMID- 22982648
TI  - Prognostic significance of tumor size in patients with stage III non-small-cell
      lung cancer: a surveillance, epidemiology, and end results (SEER) survey from
      1998 to 2003.
AB  - BACKGROUND: Increased tumor size is a known risk for poor outcomes in patients
      with stage I and II non-small cell lung cancer (NSCLC), who are treated with
      surgery or radiotherapy. However, there is limited information regarding the
      impact of tumor size on the outcomes of patients with mediastinal lymph node
      involvement. We conducted a Surveillance, Epidemiology, and End Results (SEER)
      database analysis to evaluate the prognostic significance of tumor size in
      patients with unresected stage III NSCLC. METHODS: The SEER registry was queried
      for patients with unresected NSCLC stage III and no malignant pleural effusion,
      aged 21 years or older, and diagnosed between 1998 and 2003. Tumor size was
      defined as S1 (0.1-3 cm), S2 (3.1-5 cm), S3 (5.1-7 cm), and S4 (7.1-20 cm).
      Demographic variables included age, sex, race and histology. Overall survival
      (OS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier
      method, and the Cox proportional hazard model was used to evaluate whether tumor
      size remained an independent risk factor in multivariable analysis. RESULTS: A
      total of 12,315 patients met the eligibility criteria. Median age at diagnosis
      was 70 years and most patients were men (58.7%) and white (81.3%). Tumor size was
      an independent predictor for both OS (p < 0.0001) and DSS (p < 0.001) in all
      subgroups of patients. CONCLUSION: Tumor size is an independent predictor for OS
      and DSS in patients with unresected stage III NSCLC, and should be considered in
      the stratification of patients treated in this setting after validation of this
      finding in additional studies.

PMID- 22982649
TI  - Prognostic impact of malignant pleural effusion at presentation in patients with
      metastatic non-small-cell lung cancer.
AB  - BACKGROUND: Despite its common occurrence, the influence of malignant pleural
      effusion (MPE) on the outcomes of patients with advanced non-small-cell lung
      cancer (NSCLC) with distant metastasis (M1b) is unknown. We evaluated the
      clinical characteristics associated with MPE at presentation and the prognostic
      impact of MPE at presentation in patients with stage M1b NSCLC. METHODS: We
      extracted data from the Surveillance Epidemiology and End Results (SEER) registry
      from patients with NSCLC diagnosed between 2004 and 2005. Odds-ratio estimates
      were calculated using logistic regression, and the Kaplan-Meier method was used
      to estimate the overall survival. Cox proportional hazard model was used to
      evaluate whether MPE was an independent risk for outcome. RESULTS: Among the
      57,685 patients, MPE was present in 9170 (15.9%), including 3944 out of 31,506
      (12.5%) without distant metastases and 5226 (20.0%) out of 26,179 with M1b. The
      probability of MPE was higher in patients with larger tumors, mediastinal lymph
      node involvement, and adenocarcinoma, NSCLC not otherwise specified, or large
      cell histology. In patients with stage M1b, median overall survival (3 months
      versus 5 months), estimated 1-year survival (12.6% versus 24.8%), and 2-year
      survival (5.4% versus 11.3%) were significantly lower in patients with MPE
      compared with those without MPE (hazards ratio 1.49, 95% confidence interval 1.44
      1.54, p < 0.0001). MPE was also an independent factor for worse survival in
      multivariate analysis (hazards ratio 1.36, 95% confidence interval1.30-1.43, p <
      0.001). CONCLUSIONS: MPE is a common complication in patients with NSCLC and is
      associated with decreased survival in patients with distant metastases. If these
      data are validated, subsequent studies in patients with advanced NSCLC may
      consider stratification according to the MPE status.

PMID- 22982650
TI  - Impact of systematic EGFR and KRAS mutation evaluation on progression-free
      survival and overall survival in patients with advanced non-small-cell lung
      cancer treated by erlotinib in a French prospective cohort (ERMETIC project--part
      2).
AB  - BACKGROUND: Epidermal growth factor and v-Ki-ras2 Kirsten ras sarcoma (KRAS)
      mutation status, although associated with EGFR- tyrosine kinase inhibitor (TKI)
      efficacy, has not been used in clinical practice until recently. The prospective
      Evaluation of the EGFR Mutation status for the administration of EGFR-TKIs in non
      small cell lung Carcinoma (ERMETIC) study aimed to implement these biomarkers in
      France. METHODS: Between March 2007 and April 2008, EGFR and KRAS were studied by
      sequencing DNA tumor specimens from 522 consecutive advanced non-small-cell lung
      cancer patients treated with EGFR-TKI, mostly in second- or third-line settings.
      Cox models were used to investigate the impact of patient characteristics and
      mutations on progression-free survival (PFS) and overall survival (OS). Added
      value from mutation status was evaluated using likelihood ratio (LR) tests.
      Classification and regression tree analysis aimed to identify homogeneous groups
      in terms of survival. RESULTS: Among the 522 patients, 87% were white, 32% were
      women, and 18% were never-smokers, with 65% presenting with adenocarcinoma.
      Biological data were available for 307 patients, showing 44 EGFR mutations (14%)
      and 42 KRAS (14%) mutations. Median PFS was 2.4 months (interquartile range, 1.4
      4.6) and median OS 5.6 months (interquartile range, 2.2-14.0). Factors
      independently associated with PFS were performance status 1 or 2 to 3 (hazards
      ratio [HR] = 1.5, 95% confidence interval [CI] 1.1-1.9; and HR = 2.3, CI 1.7-3.1,
      respectively; p < 0.001); former or current smoker status (HR = 1.8, CI 1.4-2.4
      and 2.0,CI 1.4-2.8, respectively; p < 0.001); nonadenocarcinoma histology
      (squamous cell: HR = 0.9 CI 0.7-1.2]; others: HR = 1.6, 1.3-2.1; p < 0.001); at
      least two metastatic sites (HR = 1.3, CI 1.1-1.6 and 1.6, CI 1.3-2.1,
      respectively; p < 0.001); prior taxane-based chemotherapy (HR = 1.3, CI 1.0-1.3,
      p = 0.01); non-white (HR = 0.7, CI 0.5-0.9, p = 0.009). Similar results were
      found for OS. In addition, EGFR and KRAS mutations were significantly associated
      with PFS (HR = 0.5, CI 0.3-0.7 and HR = 1.2, CI 0.8-1.8, respectively, versus no
      mutation; LR p = 0.001). In the OS model, adjusted HR was 0.7 (0.4-1.0) for EGFR
      mutation and 1.7 (1.1-2.4) for KRAS (LR p = 0.004). Classification and regression
      tree analysis revealed EGFR mutation to be the primary factor for identifying
      homogeneous patient subgroups in terms of PFS. CONCLUSIONS: EGFR and KRAS status
      independently impacts outcomes in advanced non-small-cell lung cancer patients
      treated with EGFR-TKI. However, EGFR status impacts both PFS and OS whereas KRAS
      only impacts OS. These findings support the nationwide use of EGFR status for
      patient selection before EGFR-TKI therapy. The role of KRAS mutations remains to
      be elucidated.

PMID- 22982651
TI  - Prediagnostic nonsteroidal anti-inflammatory drug use and lung cancer survival in
      the VITAL study.
AB  - INTRODUCTION: Inflammation is important for lung oncogenesis. Use of nonsteroidal
      anti-inflammatory drugs (NSAIDs) has been shown to improve colorectal cancer
      survival. However, few studies have examined the association in lung cancer
      patients. METHODS: The VITamins And Lifestyle (VITAL) cohort includes Washington
      State residents, aged 50 to 76 years, who completed a baseline questionnaire
      between 2000 and 2002. Participants responded on the frequency and duration of
      use of individual NSAIDs in the previous 10 years. Subjects of this study were
      785 members of the cohort, who were identified with incident lung cancer from
      baseline through 2007 through linkage to a population-based cancer registry.
      Participants were followed for lung cancer death through linkage to state records
      of death through 2009. Adjusted proportional hazards models estimated hazard
      ratios (HR) and 95% confidence intervals (CI) for the association between NSAIDs
      and lung cancer death. RESULTS: Five hundred and twenty-two participants (66%)
      died from lung cancer. Relative to nonuse, high (>= 4 days/week and >= 4 years)
      prediagnostic use of regular-strength or low-dose aspirin (HR 0.99, 95% CI: 0.74
      1.33 and HR 0.89, 95% CI: 0.67-1.17, respectively) or total nonaspirin NSAIDs (HR
      1.20, 95% CI: 0.79-1.83) did not reduce lung cancer death. However, high use of
      ibuprofen was associated with a 62% increased risk of lung cancer death (HR 1.62,
      95% CI: 1.01-2.58). CONCLUSIONS: Long-term, prediagnostic NSAID use does not
      improve lung cancer survival overall. Use of ibuprofen may reduce survival from
      lung cancer. Our results underscore the need for further study of the mechanisms
      of action for individual NSAIDs with regard to cancer survival.

PMID- 22982652
TI  - Loss of phosphatase and tensin homolog protein expression is an independent poor
      prognostic marker in lung adenocarcinoma.
AB  - INTRODUCTION: Phosphatase and tensin homolog (PTEN) has been established as a
      tumor suppressor gene with an important role in regulating the
      phosphatidylinositol-3-kinase/AKT antiapoptotic and survival pathway. The
      prognostic role of PTEN in non-small-cell lung carcinoma has not been evaluated
      completely in the context of other molecular information. METHODS: Tissue
      microarrays containing 152 resected non-small-cell lung cancer specimens were
      used to investigate PTEN and p53 by immunohistochemistry and PTEN by fluorescence
      in situ hybridization. DNA was isolated and subjected to mutational profiling
      using the Sequenom Oncocarta v1.0 panel. Clinicopathological features were
      correlated with PTEN expression, gene copy number, and mutation status. RESULTS:
      PTEN staining was absent in 63 (41.4%) of the cases. Significantly more squamous
      cell carcinomas compared with adenocarcinomas demonstrated loss of (negative)
      PTEN staining (26 of 44 [59%] versus 32 of 94 [34%]; p = 0.009). PTEN gene copy
      deletion was present in only seven of 124 evaluable cases (5.6%); all deleted
      cases were immunohistochemistry negative. In univariate and multivariate (MV)
      analyses adjusted for sex, age, histology, and stage, loss of PTEN protein
      expression was associated with significantly shorter disease-free survival (MV
      hazard ratio: 1.78, 95% confidence interval: 1.01-3.14, p = 0.048), whereas no
      significant associations were seen with p53 or KRAS and epidermal growth factor
      receptor (EGFR) mutation status. Importantly, the prognostic value of absent PTEN
      staining was limited to adenocarcinomas, with MV disease-free survival hazard
      ratio of 2.68 (95% confidence interval: 1.35-5.32, p = 0.005), whereas no such
      association was seen in squamous cell carcinomas. CONCLUSION: Absence of PTEN
      protein expression is an independent prognostic marker in early-stage resected
      lung adenocarcinoma.

PMID- 22982653
TI  - Negative NKX2-1 (TTF-1) as temporary surrogate marker for treatment selection
      during EGFR-mutation analysis in patients with non-small-cell lung cancer.
AB  - INTRODUCTION: In the past decade, major progress has been made toward
      personalized medical treatment of non-small-cell lung cancer (NSCLC) through the
      discovery of epithelial growth factor receptor (EGFR) mutations. However,
      mutation analysis takes extra time and additional costs in the diagnostic
      evaluation of lung cancer patients. It has been hypothesized that EGFR mutations
      are restricted to terminal respiratory unit -type adenocarcinoma expressing
      thyroid transcription factor-1 (official symbol NKX2-1) as determined by
      immunohistochemistry. The aim of the current study is to evaluate the potential
      of NKX2-1 immunohistochemistry as a prescreening test for EGFR mutation analysis.
      METHODS: From 2004 to December 2010, 810 consecutive NSCLC tumor specimens were
      tested for EGFR mutations in a routine diagnostic procedure. Immunohistochemistry
      for NKX2-1 was performed (clone 8G7G3/1 [Dako]) and the results were compared
      with tumor EGFR-mutation status and clinicopathological characteristics. RESULTS:
      EGFR mutations were detected in 114 specimens (14%). NKX2-1 expression was
      present in 68%. In the cases with EGFR mutation, NKX2-1 staining was positive in
      92%. NKX2-1 immunohistochemical (IHC) staining was significantly associated with
      the presence of EGFR mutations (p = 5.3*10). NKX2-1 increased the negative
      predictive value in NSCLC to more than 95%. CONCLUSIONS: In case of a negative
      NKX2-1 IHC staining, and only if clinically urgent, the high negative predictive
      value of more than 95% for EGFR mutations is a suitable temporary surrogate
      marker for the choice of starting with chemotherapy. In case of positive NKX2-1
      IHC, the best strategy is to wait for the outcome of EGFR-mutation analysis and
      then choose the appropriate treatment.

PMID- 22982654
TI  - A clinical model to estimate the pretest probability of lung cancer, based on
      1198 pedigrees in China.
AB  - INTRODUCTION: Computed tomography screening can detect lung cancer that is
      curable. However, some studies demonstrated that the risk for false-positives was
      about 50%. To make screening more efficient, we sought to create a forecasting
      model for individuals with different risks for lung cancer. METHODS: We used
      multiple logistic regression analysis to identify independent predictors and to
      develop a prediction model. The pathological diagnoses in Guangdong Lung Cancer
      Institute were consecutively chosen as probands. All first-degree relatives of
      probands and their spouses were included as subjects. We divided the probands and
      their spouses into three subgroups according to the odds ratios (ORs), and the
      accuracy of lung cancer predictions for patients within the subgroups increased
      synchronously. RESULTS: There were 633 proband pedigrees and 565 spouse
      pedigrees. Independent predictors of lung cancer included sex (OR, 1.6; 95%
      confidence interval [CI], 1.1-2.3), smoking history (light smoker: OR, 1.1; 95%
      CI, 0.7-1.8; heavy smoker: OR, 4.7; 95% CI, 3.1-7.1), lung disease history (OR,
      5.3; 95% CI, 2.8-10.0), occupational exposure (OR, 1.6; 95% CI, 1.1-2.2), and
      number of affected individuals among first-degree relatives (n = 1: OR, 2.1; 95%
      CI, 1.3-3.4; n >= 2: OR, 4.7; 95% CI, 0.5-41.2). The accuracy of the pretest
      probability increased for those with higher ORs: low-OR subgroup, 68.3%; mid-OR
      subgroup, 84.0%; and high-OR subgroup, 91.9%. CONCLUSIONS: Our prediction rule is
      recommended for estimating the pretest probability of lung cancer, thereby
      facilitating early screening.

PMID- 22982655
TI  - Radical treatment of non-small-cell lung cancer patients with synchronous
      oligometastases: long-term results of a prospective phase II trial (Nct01282450).
AB  - BACKGROUND: Stage IV non-small-cell lung cancer (NSCLC) patients with
      oligometastases (< 5 metastatic lesions) may experience long-term survival when
      all macroscopic tumor sites are treated radically, but no prospective data on
      NSCLCs with synchronous oligometastases are available. METHODS: A prospective
      single-arm phase II trial was conducted. The main inclusion criteria were
      pathologically proven NSCLC stage IV with less than five metastases at primary
      diagnosis, amendable for radical local treatment (surgery or radiotherapy). The
      study is listed in clinicaltrials.gov, number NCT01282450. RESULTS: Forty
      patients were enrolled, 39 of whom were evaluable (18 men, 21 women); mean age
      was 62.1 +/- 9.2 years (range, 44-81). Twenty-nine (74%) had local stage III; 17
      (44%) brain, seven (18%) bone, and four (10%) adrenal gland metastases. Thirty
      five (87%) had a single metastatic lesion. Thirty-seven (95%) of the patients
      received chemotherapy as part of their primary treatment. Median overall survival
      (OS) was 13.5 months (95% confidence interval 7.6-19.4); 1-, 2-, and 3-year OS
      was 56.4%, 23.3%, and 17.5%, respectively. Median progression-free survival (PFS)
      was 12.1 months (95% confidence interval 9.6-14.3); 1-year PFS was 51.3%, and
      both 2- and 3-year PFS was 13.6%. Only two patients (5%) had a local recurrence.
      No patient or tumor parameter, including volume and F-deoxyglucose uptake was
      significantly correlated with OS or PFS. The treatment was well tolerated.
      CONCLUSION: In this phase II study, long-term PFS was found in a subgroup of
      NSCLC patients with synchronous oligometastases when treated radically.
      Identification of this favorable subgroup before therapy is needed.

PMID- 22982656
TI  - Completion pneumonectomy in patients with cancer: postoperative survival and
      mortality factors.
AB  - OBJECTIVE: To describe postoperative complications and long-term outcomes of
      completion pneumonectomy and highlight prognostic factors. METHOD: We
      retrospectively reviewed the records of 46 patients (38 men, 8 women) who
      underwent completion pneumonectomy for lung cancer between 1995 and 2009 in one
      of two thoracic surgery departments. Most were current or former smokers (n = 41;
      89%) and did not undergo chemotherapy (n = 38; 83%) or radiotherapy (83%) before
      surgery. RESULTS: Complications after surgery were respiratory failure (n = 11;
      24.4%), bronchopleural fistula (n = 6; 13%, with no side preference), and empyema
      (n = 6; 13%). Blood transfusion was necessary for 43% of the cases (n = 20). The
      day 90 death rate was 15.2% (n = 7). Postoperative staging showed mostly limited
      disease. Ten patients (21.7%) underwent operation for a second primary cancer, 25
      for local recurrence (54.3%), five for microscopically incomplete resection, and
      six for other reasons. Median overall survival after completion surgery was 30
      months (median follow-up: 46.5 months). Among the 15 living patients (33%), 11
      are free of disease (24%). In a Cox regression model, factors negatively
      influencing overall survival were: age older than 65 years (odds ratio [OR] =
      2.47; p = 0.012), current smoker status (OR = 2.285; p = 0.033), postoperative
      pulmonary (OR = 5.144; p = 0.004), cardiac (OR = 3.404; p = 0.033), or parietal
      wound complications (OR = 5.439; p = 0.016). CONCLUSION: Despite its increased
      postoperative complications and mortality compared with standard pneumonectomy,
      completion pneumonectomy offers encouraging long-term results. Five main factors
      seem predictive of shorter overall survival.

PMID- 22982657
TI  - Quality of life evolution after pulmonary metastasectomy: a prospective study
      comparing isolated lung perfusion with standard metastasectomy.
AB  - OBJECTIVE: To prospectively evaluate quality of life (QoL) evolution after a
      classic pulmonary metastasectomy or after an isolated lung perfusion (ILuP)
      metastasectomy. METHODS: QoL was prospectively recorded in 35 consecutive
      patients (27 classic metastasectomy; 8 ILuP) The European Organisation for
      Research and Treatment of Cancer C30 and lung cancer -13 QoL Questionnaires were
      administered before surgery and 1, 3, 6 and 12 months postoperatively (MPO).
      RESULTS: After a classic metastasectomy, a temporary increase in dyspnea (1 MPO p
      = 0.03 3 MPO p = 0.01), coughing (3 MPO p = 0.01), fatigue (1 MPO p = 0.01, 3 MPO
      p = 0.02), thoracic pain (1 MPO, p = 0.02), shoulder dysfunction (1 MPO p = 0.03,
      3 MPO p = 0.02) as well as an impaired physical (1 MPO p = 0.01, 3 MPO p = 0.04)
      and role functioning (1 MPO p = 0.01, 3 MPO p = 0.01) was reported the first 3
      months after surgery. Six months after surgery, all domains returned to baseline.
      After ILuP metastasectomy, all QoL functioning and symptom scores, except for
      coughing complaints (1 MPO p = 0.03, 3 MPO p = 0.04) and shoulder dysfunction (1
      MPO p = 0.04, 6 MPO p = 0.04), returned to baseline at 1 month after surgery. No
      significant differences were seen when QoL evolution was compared between classic
      and ILuP metastasectomy with the exception of a higher burden of thoracic pain (6
      MPO p = 0.04, 12 MPO p = 0.01), shoulder dysfunction (6 MPO p = 0.04, 12 MPO p =
      0.02), and dysphagia (6 MPO p = 0.04, 12 MPO p = 0.02) 6 and12 months after ILuP.
      CONCLUSIONS: All QoL domains returned to baseline at 6 months after a classic
      metastasectomy. After ILuP, only increases in coughing and shoulder dysfunction
      were reported. In comparison classic metastasectomy patients, ILuP patients
      report more thoracic pain, shoulder dysfunction, and dysphagia.

PMID- 22982658
TI  - A double-blind randomized discontinuation phase-II study of sorafenib (BAY 43
      9006) in previously treated non-small-cell lung cancer patients: eastern
      cooperative oncology group study E2501.
AB  - INTRODUCTION: Sorafenib is a raf kinase and angiogenesis inhibitor with activity
      in multiple cancers. This phase-II study in heavily pretreated non-small-cell
      lung cancer (NSCLC) patients (>= 2 prior therapies) used a randomized
      discontinuation design. METHODS: Patients received 400 mg of sorafenib orally
      twice daily for two cycles (2 months) (step 1). Responding patients on step 1
      continued on sorafenib; progressing patients went off study, and patients with
      stable disease were randomized to placebo or sorafenib (step 2), with crossover
      from placebo allowed upon progression. The primary endpoint of this study was the
      proportion of patients having stable or responding disease 2 months after
      randomization. RESULTS: There were 299 patients evaluated for step 1; of these,
      81 eligible patients were randomized on step 2 and received sorafenib (n = 50) or
      placebo (n = 31). The 2-month disease control rates after randomization were 54%
      and 23% for patients initially receiving sorafenib and placebo, respectively, p =
      0.005. The hazard ratio for progression on step 2 was 0.51 (95% [confidence
      interval] CI 0.30, 0.87, p = 0.014) favoring sorafenib. A trend in favor of
      overall survival with sorafenib was also observed (13.7 versus 9.0 months from
      time of randomization), hazard ratio 0.67 (95% CI 0.40-1.11), p = 0.117. A
      dispensing error occurred, which resulted in the unblinding of some patients, but
      not before completion of the 8-week initial step 2 therapy. Toxicities were
      manageable and as expected. CONCLUSIONS: The results of this randomized
      discontinuation trial suggest that sorafenib has single-agent activity in a
      heavily pretreated, enriched patient population with advanced NSCLC. These
      results support further investigation with sorafenib as a single agent in larger,
      randomized studies in NSCLC.

PMID- 22982659
TI  - Effects of pharmacokinetic processes and varied dosing schedules on the dynamics
      of acquired resistance to erlotinib in EGFR-mutant lung cancer.
AB  - INTRODUCTION: Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor, which effectively targets EGFR-mutant driven non-small
      cell lung cancer. However, the evolution of acquired resistance because of a
      second-site mutation (T790M) within EGFR remains an obstacle to successful
      treatment. METHODS: We used mathematical modeling and available clinical trial
      data to predict how different pharmacokinetic parameters (fast versus slow
      metabolism) and dosing schedules (low dose versus high dose; missed doses with
      and without make-up doses) might affect the evolution of T790M-mediated
      resistance in mixed populations of tumor cells. RESULTS: We found that high-dose
      pulses with low-dose continuous therapy impede the development of resistance to
      the maximum extent, both pre- and post-emergence of resistance. The probability
      of resistance is greater in fast versus slow drug metabolizers, suggesting a
      potential mechanism, unappreciated to date, influencing acquired resistance in
      patients. In case of required dose modifications because of toxicity, little
      difference is observed in terms of efficacy and resistance dynamics between the
      standard daily dose (150 mg/d) and 150 mg/d alternating with 100 mg/d. Missed
      doses are expected to lead to resistance faster, even if make-up doses are
      attempted. CONCLUSIONS: For existing and new kinase inhibitors, this novel
      framework can be used to rationally and rapidly design optimal dosing strategies
      to minimize the development of acquired resistance.

PMID- 22982660
TI  - DNA repair polymorphisms and treatment outcomes of patients with malignant
      mesothelioma treated with gemcitabine-platinum combination chemotherapy.
AB  - INTRODUCTION: Genetic polymorphisms that affect DNA repair capacity can modulate
      the efficacy and toxicity of cytotoxic agents. Therefore, the aim of our study
      was to evaluate the influence of genetic variability in DNA repair genes on
      treatment outcome in patients with malignant mesothelioma (MM) treated with
      gemcitabine-platinum combination chemotherapy. METHODS: In total, 109 patients
      with MM were genotyped for 10 polymorphisms in XRCC1, NBN, RAD51, and XRCC3
      genes. The influence of selected polymorphisms on tumor response and occurrence
      of treatment-related toxicity was determined by logistic regression analysis,
      whereas their influence on survival was estimated by Cox proportional hazards
      model. RESULTS: There were no associations between the investigated polymorphisms
      and tumor response, but we observed a significant association between XRCC1
      399Gln allele and reduced overall survival (hazards ratio = 1.70; 95% confidence
      interval [CI] 1.06-2.73; p = 0.028). Interaction between XRCC1 399Gln allele and
      C-reactive protein levels revealed that carriers of at least one XRCC1 399Gln
      allele with C-reactive protein levels above median had significantly shorter
      overall survival time compared with other patients (12.9 months versus 25.3
      months, log-rank p < 0.001). We also observed an association between XRCC1 399Gln
      and lower frequency of leukopenia (odds ratio [OR] = 0.25; 95% CI 0.09-0.67; p =
      0.006), neutropenia (OR = 0.24; 95% CI 0.09-0.68; p = 0.007), and
      thrombocytopenia (OR = 0.27; 95% CI 0.09-0.84; p = 0.024). In addition, NBN
      3474A>C, XRCC3 -316A>G, and Thr241Met polymorphisms showed significant
      associations with treatment-related toxicity. CONCLUSIONS: Our results support
      the hypothesis that DNA repair gene polymorphisms, particularly XRCC1 Arg399Gln,
      may modify the response to gemcitabine-platinum combination chemotherapy and, for
      the first time, show this effect in patients with MM.

PMID- 22982661
TI  - Multicenter trial of EC145 in advanced, folate-receptor positive adenocarcinoma
      of the lung.
AB  - BACKGROUND: EC145 is a novel folate-receptor targeted agent consisting of a
      folate molecule linked to a vinca alkaloid. EC20 is a technetium-labeled folate
      that assesses the presence of folate receptors (FR) in vivo. The objective of
      this study was to determine the activity of EC145 in patients with chemotherapy
      refractory lung adenocarcinoma, whose tumors expressed the FR as determined by
      EC20 imaging. METHODS: Patients with advanced adenocarcinoma of the lung, Eastern
      Cooperative Oncology Group performance status 0 to 2, normal organ function,
      those who had progressed after at least two prior cytotoxic regimens, and with EC
      20 uptake in at least one index lesion were eligible. The primary objective of
      the study was the ability to receive four or more cycles of therapy. RESULTS:
      Sixty patients were screened and 43 patients were enrolled. Eleven patients (26%)
      received more than four cycles (95% confidence interval [CI] 14%, 41%), and one
      patient had partial response (response rate (RR) = 2.3%, 95% CI 0%, 12%).
      Patients in whom all target tumor lesions expressed FR by EC 20 scans had a trend
      toward superior results in terms of clinical benefit response (50% versus 14.3 %;
      p = 0.10) and survival (47.2 weeks versus 14.9 weeks [HR = 0.539, p = 0.101])
      compared with those in whom at least one but not all target lesions were positive
      for FR (FR+). CONCLUSION: EC145 demonstrated clinical activity with a good
      toxicity profile in this population. Uniform uptake of EC20 may predict activity
      of EC145 and be useful for prospective selection of patients in future trials.

PMID- 22982662
TI  - Bronchoesophageal fistula in a patient with stage IIIB non-small-cell lung
      cancer.

PMID- 22982663
TI  - EGFR delE709_T710insD: a rare but potentially EGFR inhibitor responsive mutation
      in non-small-cell lung cancer.

PMID- 22982664
TI  - Malignant pleural mesothelioma localized in the thoracic wall.

PMID- 22982665
TI  - Efficacy of positron emission tomography staging for small-cell lung cancer: a
      systematic review and cost analysis in the Australian setting.

PMID- 22982667
TI  - RhoA affects oral morphine analgesia depending on functional variation in
      intestinal P-glycoprotein induced by repeated etoposide treatment.
AB  - In early palliative care, drug-drug interactions between opioids and anticancer
      agents may be caused by combined treatment with these drugs. We previously
      reported that repeated administration of oral etoposide (ETP), an anticancer drug
      that is a substrate of P-glycoprotein (P-gp), caused attenuation of the analgesic
      effect of oral morphine through up-regulation of intestinal P-gp. Recent studies
      have revealed that RhoA, a small G-protein, is involved in the regulation of P-gp
      expression and activity. Moreover, RhoA is known to be involved in various
      signaling pathways in response to anticancer drugs. Here, we examined the
      involvement of RhoA in the changes in ileal P-gp protein expression and activity
      induced by repeated orally administered ETP. Ileal P-gp and RhoA protein
      expression levels were analyzed using western blot analysis. The efflux activity
      of ileal P-gp was measured using the in situ closed loop method. The analgesic
      effect of oral morphine was determined with a tail-flick test. Repeated oral ETP
      significantly increased the activity of RhoA in association with up-regulation of
      P-gp protein expression and activity in the ileum. Interestingly, inhibition of
      RhoA activation by rosuvastatin prevented these effects. Furthermore, ETP-induced
      attenuation of the analgesic effect of oral morphine was also suppressed by
      rosuvastatin. RhoA activation induced by repeated oral ETP administration may be
      involved in the up-regulation of ileal P-gp protein expression and activity,
      leading to a decrease in the analgesic effect of oral morphine.

PMID- 22982669
TI  - Loss of Drosophila A-type lamin C initially causes tendon abnormality including
      disintegration of cytoskeleton and nuclear lamina in muscular defects.
AB  - Lamins are the major components of nuclear envelope architecture, being required
      for both the structural and informational roles of the nuclei. Mutations of
      lamins cause a spectrum of diseases in humans, including muscular dystrophy. We
      report here that the loss of the A-type lamin gene, lamin C in Drosophila
      resulted in pupal metamorphic lethality caused by tendon defects, matching the
      characteristics of human A-type lamin revealed by Emery-Dreifuss muscular
      dystrophy (EDMD). In tendon cells lacking lamin C activity, overall cell
      morphology was affected and organization of the spectraplakin family cytoskeletal
      protein Shortstop which is prominently expressed in tendon cells gradually
      disintegrated, notably around the nucleus and in a manner correlating well with
      the degradation of musculature. Furthermore, lamin C null mutants were
      efficiently rescued by restoring lamin C expression to shortstop-expressing
      cells, which include tendon cells but exclude skeletal muscle cells. Thus the
      critical function of A-type lamin C proteins in Drosophila musculature is to
      maintain proper function and morphology of tendon cells.

PMID- 22982668
TI  - Rargb regulates organ laterality in a zebrafish model of right atrial isomerism.
AB  - Developmental signals determine organ morphology and position during
      embryogenesis. To discover novel modifiers of liver development, we performed a
      chemical genetic screen in zebrafish and identified retinoic acid as a positive
      regulator of hepatogenesis. Knockdown of the four RA receptors revealed that all
      receptors affect liver formation, however specific receptors exert differential
      effects. Rargb knockdown results in bilateral livers but does not impact organ
      size, revealing a unique role for Rargb in conferring left-right positional
      information. Bilateral populations of hepatoblasts are detectable in rargb
      morphants, indicating Rargb acts during hepatic specification to position the
      liver, and primitive endoderm is competent to form liver on both sides. Hearts
      remain at the midline and gut looping is perturbed in rargb morphants, suggesting
      Rargb affects lateral plate mesoderm migration. Overexpression of Bmp during
      somitogenesis similarly results in bilateral livers and midline hearts, and
      inhibition of Bmp signaling rescues the rargb morphant phenotype, indicating
      Rargb functions upstream of Bmp to regulate organ sidedness. Loss of rargb causes
      biliary and organ laterality defects as well as asplenia, paralleling symptoms of
      the human condition right atrial isomerism. Our findings uncover a novel role for
      RA in regulating organ laterality and provide an animal model of one form of
      human heterotaxia.

PMID- 22982670
TI  - Cytoprotective properties of traditional Chinese medicinal herbal extracts in
      hydrogen peroxide challenged human U373 astroglia cells.
AB  - Age is the leading risk factor for many of the most prevalent and devastating
      diseases including neurodegenerative diseases. A number of herbal medicines have
      been used for centuries to ameliorate the deleterious effects of ageing-related
      diseases and increase longevity. Oxidative stress is believed to play a role in
      normal ageing as well as in neurodegenerative processes. Since many of the
      constituents of herbal extracts are known antioxidants, it is believed that
      restoring oxidative balance may be one of the underlying mechanisms by which
      medicinal herbs can protect against ageing and cognitive decline. Based on the
      premise that astrocytes are key modulators in the progression of oxidative stress
      associated neurodegenerative diseases, 13 herbal extracts purported to possess
      anti-ageing properties were tested for their ability to protect U373 human
      astrocytes from hydrogen peroxide induced cell death. To determine the
      contribution of antioxidant activity to the cytoprotective ability of extracts,
      total phenol content and radical scavenging capacities of extracts were examined.
      Polygonum multiflorum, amongst others, was identified as possessing potent
      antioxidant and cytoprotective properties. Not surprisingly, total phenol content
      of extracts was strongly correlated with antioxidant capacity. Interestingly,
      when total phenol content and radical scavenging capacities of extracts were
      compared to the cytoprotective properties of extracts, only moderately strong
      correlations were observed. This finding suggests the involvement of multiple
      protective mechanisms in the beneficial effects of these medicinal herbs.

PMID- 22982671
TI  - Adipose-derived stem cells induced dendritic cells undergo tolerance and inhibit
      Th1 polarization.
AB  - Adipose tissue-derived stem cells (ADSC) have been shown to possess stem cell
      properties such as transdifferentiation, self-renewal and therapeutic potential.
      However, the property of ADSC to accommodate immune system is still unknown. In
      this study, ADSC were cocultured with allogenetic dendritic cells (DC), and then
      treated DC were mixed with allogenetic CD4+ T cells. The results demonstrated
      that ADSC could downregulate costimulatory molecules, including CD80, CD83, CD86,
      and cytokine secretion such as interleukin (IL)-12 and tumor necrosis factor
      (TNF)-alpha, while upregulate indoleamine-2,3-dioxygenase (IDO) of allogenetic
      DC. In addition, treated DC could inhibit CD4+ T cell activation and naive T
      cells toward Th1 polarization. The results suggest that ADSC could negatively
      modulate immunity and induce immune tolerance, which provide a promising strategy
      in transplantation or autoimmune disease.

PMID- 22982672
TI  - Sex ratio adjustment by sex-specific maternal cannibalism in hamsters.
AB  - Mammalian offspring sex ratios can be biased via prenatal and postnatal
      mechanisms, including sperm selection, sex-specific embryo loss, and differential
      postnatal investment in males and females. Syrian hamsters routinely cannibalize
      some of their pups in the first days after birth. We present evidence that short
      day lengths, typically predictive of poor autumn and winter field conditions, are
      associated with male-biased sex ratios, achieved in part through selective
      perinatal maternal infanticide of female offspring. Higher peak litter sizes were
      associated with increased cannibalism rates, decreased final litter counts, and
      increased body mass of pups surviving to weaning. To our knowledge this is the
      first report of sex ratio adjustment by offspring cannibalism.

PMID- 22982673
TI  - Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates
      tumor growth by inhibiting apoptosis of breast cancer cells and is associated
      with a poor prognosis in breast cancer patients.
AB  - BACKGROUND: Ubiquitous mitochondrial creatine kinase (uMtCK), a mitochondrial
      isoenzyme of creatine kinase (CK), is a central controller of cellular energy
      homeostasis. Overexpression of uMtCK has been reported to be associated with a
      poor prognosis for several tumors. The aim of this study was to assess its
      association with breast cancer (BCa) and to further investigate its underlying
      mechanisms. METHOD: We first detected uMtCK expression by immunohistochemistry in
      human BCa tissues and assessed the association with the prognosis of patients. We
      then evaluated uMtCK expression in crowded and normal condition cultures of
      several human BCa cell lines. After two stable clones of the MDA-MB-231 cell line
      with high expression of uMtCK were established, cell growth, apoptosis and
      mitochondrial apoptotic pathway protein expression were measured in these clones.
      Finally, tumorigenicity of the above cells was assessed using nude mice to
      explore the relationship between uMtCK expression and tumor progression. RESULTS:
      uMtCK expression was detected in 85.5% (47 of 55) of the invasive ductal
      carcinomas of breast tissue, not otherwise specified (IDC-NOS). Expression in BCa
      tissue was significantly associated with reduced progression-free survival (PFS;
      P=0.019) and overall survival (OS; P=0.022) of the patients. Up-regulation of
      uMtCK expression was identified in crowded BCa cells in culture, and the number
      of apoptotic cells was significantly decreased in uMtCK transfected MDA-MB-231
      cell clones (P<0.01). Stabilization of the mitochondrial membrane potential
      (DeltaPsim) and down regulation of cytochrome c (cyt c) and activated caspase 9,
      two components of mitochondrial apoptotic pathway proteins, were also identified
      in the same clones when cells were crowded in culture. In vivo studies revealed
      that the transfected tumor cells with uMtCK overexpression induced faster tumor
      growth in nude mice, along with accelerated animal body weight loss and a
      significantly lower tumor apoptotic index (AI) (P<0.001). CONCLUSION: The results
      indicated that uMtCK expression is associated with a poor prognosis in BCa and
      might serve as a tumor marker. In vivo and In vitro evidence suggests that uMtCK
      overexpression promotes tumor growth by inhibiting apoptosis of tumor cells
      through stabilizing DeltaPsim and down regulating mitochondrial apoptotic pathway
      proteins. Exploration of therapeutic agents targeting the expression of uMtCK may
      have practical value for BCa patients.

PMID- 22982674
TI  - High-expression of ZBP-89 correlates with distal metastasis and poor prognosis of
      patients in clear cell renal cell carcinoma.
AB  - ZBP-89, a Kruppel-type zinc-finger transcription factor, is found to participate
      in tumor development, invasion and metastasis. However, the expression status of
      ZBP-89 in clear cell renal cell carcinoma (CCRCC) remains elusive. Using
      quantitative real-time-PCR and Western Blot, we found that, in fresh cancer
      tissues, ZBP-89 was remarkably decreased in 79.2% (19/24) and 83.3% (5/6) of
      CCRCC at mRNA and protein level, respectively. Immunohistochemistry also revealed
      a significant decline of ZBP-89 expression in CCRCC, showing that low expression
      of ZBP-89 was present in 73.9% (105/142) of tumorous tissues but in 48.1%
      (52/108) of the corresponding adjacent kidney tissues. Furthermore, ZBP-89
      expression in CCRCC was significantly correlated with several clinicopathological
      features, including TNM stage (P=0.005) and distal metastasis (P=0.001). Further
      study confirmed that ZBP-89 expression was markedly higher in metastatic CCRCC
      than that in non-metastatic tissue (P=0.002). In addition, CCRCC patients with
      low ZBP-89 expression survived longer than those with high ZBP-89 expression, as
      indicated by the result of univariate analysis (P<0.0001). More importantly,
      multivariate analysis revealed that ZBP-89 was an independent predictor of
      overall survival (HR, 2.871; 95% CI, 1.409-5.853; P=0.004). Collectively, our
      study provides vigorous evidence that ZBP-89 was significantly downregulated in
      CCRCC and could be served as a promising biomarker for prediction of distal
      metastasis and prognosis of patient with CCRCC.

PMID- 22982675
TI  - Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal
      carcinoma Caki cells.
AB  - Withaferin A, the active component of Withania somnifera, causes cytotoxicity in
      a variety of tumor cell lines. In this study, we show that withaferin A inhibits
      constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705), but not IFN
      gamma-induced STAT1 phosphorylation. Withaferin A-induced down-regulation of
      STAT3 activation is associated with a reduction in Janus-activated kinase 2
      (JAK2) activity. Withaferin A also down-regulates the expression of STAT3
      regulated genes such as Bcl-xL, Bcl-2, cyclin D1 and survivin. The apoptotic
      effect of withaferin A in Caki human renal cancer cells was investigated.
      Withaferin A induced dose-dependent apoptotic cell death in Caki cells, as
      measured by FACS analysis and PARP cleavage. Furthermore, overexpression of STAT3
      attenuated withaferin A-induced apoptosis. Taken together, the present study
      provides strong evidence that down-regulation of the STAT3 signaling pathway
      mediates withaferin A-induced apoptosis.

PMID- 22982676
TI  - Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1 secreting
      cells.
AB  - BACKGROUND: Evidence is emerging that elevated serum free fatty acids
      (hyperlipidemia) contribute to the pathogenesis of type-2-diabetes, and
      lipotoxicity is observed in many cell types. We recently published data
      indicating lipotoxic effects of simulated hyperlipidemia also in GLP-1-secreting
      cells, where the antidiabetic drug metformin conferred protection from
      lipoapoptosis. The aim of the present study was to identify mechanisms involved
      in mediating lipotoxicity and metformin lipoprotection in GLP-1 secreting cells.
      These signaling events triggered by simulated hyperlipidemia may underlie reduced
      GLP-1 secretion in diabetic subjects, and metformin lipoprotection by metformin
      could explain elevated plasma GLP-1 levels in diabetic patients on chronic
      metformin therapy. The present study may thus identify potential molecular
      targets for increasing endogenous GLP-1 secretion through enhanced viability of
      GLP-1 secreting cells in diabetic hyperlipidemia and obesity. METHODS: We have
      studied molecular mechanisms mediating lipotoxicity and metformin-induced
      lipoprotection in GLP-1-secreting L-cells in vitro, using the murine GLUTag cell
      line as a model. Diabetic hyperlipidemia was simulated in this cell system by
      addition of the fatty acid palmitate. Caspase-3 activity was used as a measure of
      GLUTag cell apoptosis. ROS production was determined using a fluorescent probe,
      and the activation of intracellular signaling pathways was assessed by Western
      blotting. RESULTS: Palmitate increased ROS production in GLP-1 secreting cells,
      and the lipotoxic effects of palmitate were abolished in the presence of the
      antioxidant Trolox. Further, palmitate phosphorylated p38 and inhibition of p38
      using the p38 inhibitor SB203580 significantly reduced palmitate-induced caspase
      3 activity. Pre-incubation of palmitate with metformin further increased
      palmitate induced ROS production, while significantly reducing the expression of
      p38. CONCLUSION: This study demonstrates that palmitate induces ROS production
      and that the palmitate induced lipotoxicity is the result of increased ROS
      production, where the ROS sensitive MKK3/6-p38 pathway mediates lipoapoptosis of
      GLP-1-secreting cells. Further, in the presence of simulated hyperlipidemia,
      metformin increases ROS production. However, metformin significantly decreases
      the expression of p38, indicating that metformin mediated lipoprotection involves
      reduced activity of the p38 signaling pathway.

PMID- 22982677
TI  - Involvement of the transcription factor FoxM1 in contact inhibition.
AB  - Contact inhibition is a crucial mechanism regulating proliferation in vitro and
      in vivo. Although it is generally accepted that contact inhibition plays a
      pivotal role in maintaining tissue homeostasis, the molecular mechanisms of
      contact inhibition are still not fully understood. FoxM1 is known as a
      proliferation-associated transcription factor and is upregulated in many cancer
      types. Vice versa, anti-proliferative signals, such as TGF-beta and
      differentiation signals decrease FoxM1 expression. Here we investigated the role
      of FoxM1 in contact inhibition in fibroblasts. We show that protein expression of
      FoxM1 is severely and rapidly downregulated upon contact inhibition, probably by
      inhibition of ERK activity, which then leads to decreased expression of cyclin A
      and polo-like kinase 1. Vice versa, ectopic expression of FoxM1 prevents the
      decrease in cyclin A and polo-like kinase 1 and causes a two-fold increase in
      saturation density indicating loss of contact inhibition. Hence, we show that
      downregulation of FoxM1 is required for contact inhibition by regulating
      expression of cyclin A and polo-like kinase 1.

PMID- 22982678
TI  - New insights into Dok-4 PTB domain structure and function.
AB  - The seven members of the Dok adapter protein family share a highly conserved
      phosphotyrosine-binding (PTB) domain. In the case of Dok-1, 2 and 3, the PTB
      domain binds to the lipid phosphatase Ship1, a key component of their inhibitory
      signaling mechanisms in immune cells. In contrast to most other Dok family
      members, Dok-4 is expressed widely but is poorly understood, largely because of
      limited knowledge of its partner molecules. We previously showed that, in
      contrast to the Dok-1 PTB domain (defined as aa 107-260), the homologous sequence
      in Dok-4 (aa 100-233) bound very poorly to Ret, a known Dok-4 partner. In the
      current study, we show that binding of Dok-4 to Ret requires residues C-terminal
      to the previously defined PTB domain boundaries (up to aa 246). These residues
      are predicted to form an extension in a critical C-terminal alpha-helix. We show
      that the Dok-4 PTB domain also binds the phosphorylated NPXY motifs in Ship1 but
      not Ship2. Finally, we found that a rare human single nucleotide polymorphism
      causing a R186H substitution in the PTB domain abolishes tyrosine phosphorylation
      of Dok-4 by Ret. In addition to providing a clearer understanding of Dok-4 PTB
      domain structure and function, our findings point to a potential mechanism for
      Dok-4 inhibitory signaling in T-cells and to the possibility of a rare Dok-4
      related phenotype in humans.

PMID- 22982679
TI  - Selection of valid reference genes for expression studies of hepatic cell lines
      under IFN-alpha treatment.
AB  - The proper selection of reference genes to normalize the quantitative real-time
      PCR (RT-qPCR) results under particular experimental conditions is crucial for
      validation of the gene quantification data. Herein, using SYBR green RT-qPCR,
      five reference genes (GAPDH, ACTB, HMBS, HPRT-1 and TBP) were evaluated to
      determine the most stable reference genes in hepatic cell lines (Huh-7 and
      HepG(2)) under IFN-alpha treatment conditions. Analyses by geNorm program ranked
      GAPDH and HPRT-1 in Huh-7 and that of ACTB and HMBS in HepG(2) cells as the most
      stable reference genes under IFN-alpha treatment. While, same reference gene
      pairs were ranked by NormFinder program in Huh-7 cells, GAPDH was assessed as the
      most stable gene in HepG(2) group by this program, implying the importance of the
      employed algorithm in comparative interpretation of the data. Finally, cumulative
      analyses by one-way ANOVA, geNorm and NormFinder programs indicated that use of
      two reference genes (HMBS and GAPDH) in Huh-7 and three (HMBS, ACTB and GAPDH) in
      HepG(2) cells would greatly improve the normalization of the RT-qPCR data under
      IFN-alpha. Data presented in this paper will aid the selection of the most stable
      reference genes in RT-qPCR studies on evaluation of hepatic viral proteins and
      IFN pathway.

PMID- 22982680
TI  - Characterization of p75(+) ectomesenchymal stem cells from rat embryonic facial
      process tissue.
AB  - Several populations of stem cells, including those from the dental pulp and
      periodontal ligament, have been isolated from different parts of the tooth and
      periodontium. The characteristics of such stem cells have been reported as well.
      However, as a common progenitor of these cells, ectomesenchymal stem cells
      (EMSCs), derived from the cranial neural crest have yet to be fully
      characterized. The aim of this study was to better understand the characteristics
      of EMSCs isolated from rat embryonic facial processes. Immunohistochemical
      staining showed that EMSCs had migrated to rat facial processes at E11.5, while
      the absence of epithelial invagination or tooth-like epithelium suggested that
      any epithelial-mesenchymal interactions were limited at this stage. The p75
      neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select
      p75NTR-positive EMSCs (p75(+) EMSCs), which were found to show a homogeneous
      fibroblast-like morphology and little change in the growth curve, proliferation
      capacity, and cell phenotype during cell passage. They also displayed the
      capacity to differentiate into diverse cell types under chemically defined
      conditions in vitro. p75(+) EMSCs proved to be homogeneous, stable in vitro and
      potentially capable of multiple lineages, suggesting their potential for
      application in dental or orofacial tissue engineering.

PMID- 22982681
TI  - CAC1 negatively regulates RARalpha activity through cooperation with HDAC.
AB  - Retinoic acid (RA) plays pleiotropic roles in cellular differentiation and animal
      development. RA responses are mediated by transcriptional activation by the
      retinoic acid receptor (RAR) and retinoid X receptor (RXR) in cooperation with
      various types of coregulators at RA-responsive gene promoters. Here, we
      identified CDK2-associated cullin (CAC1) as a novel type of RARalpha coregulator
      that interacts with RARalpha and inhibits its transcriptional activity. The CoRNR
      box of CAC1 is required for the binding to and inactivation of RARalpha. In
      addition, CAC1 cooperates with histone deacetylases (HDACs) to suppress RARalpha,
      probably by associating with HDAC. Finally, depletion of CAC1 increases RA
      induced neuronal differentiation of P19 cells, a response accompanied by
      significant upregulation of the neuronal marker nestin. From these results, we
      suggest that CAC1 is a novel corepressor of RARalpha that cooperates with HDACs
      and is involved in the regulation of RA-induced cellular differentiation.

PMID- 22982682
TI  - Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self
      administration and cocaine-seeking behavior in rats.
AB  - Neuropeptide S (NPS) is a neuromodulatory peptide, acting via a G-protein-coupled
      receptor to regulate sleep, anxiety and behavioral arousal. Recent research has
      found that intracerebroventricular NPS can increase cocaine and alcohol self
      administration in rodents, suggesting a key role in reward-related
      neurocircuitry. It is hypothesized that antagonism of the NPS system might
      represent a novel strategy for the pharmacological treatment of cocaine abuse. To
      this end, a small-molecule NPSR antagonist (RTI-118) was developed and tested in
      animal models of cocaine seeking and cocaine taking. Male Wistar rats (n=54)
      trained to self-administer cocaine and food under a concurrent alternating FR4
      schedule exhibited specific dose-dependent decreases in cocaine intake when
      administered RTI-118. RTI-118 also decreased the reinstatement of extinguished
      cocaine-seeking behavior induced by conditioned cues, yohimbine and a priming
      dose of cocaine. These data support the hypothesis that antagonism of the
      neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and
      relapse.

PMID- 22982683
TI  - Incorporating biological, chemical, and toxicological knowledge into predictive
      models of toxicity.

PMID- 22982684
TI  - Comparative gene expression profiling in human-induced pluripotent stem cell-
      derived cardiocytes and human and cynomolgus heart tissue.
AB  - Cardiotoxicity is one of the leading causes of drug attrition. Current in vitro
      models insufficiently predict cardiotoxicity, and there is a need for alternative
      physiologically relevant models. Here we describe the gene expression profile of
      human-induced pluripotent stem cell-derived cardiocytes (iCC) postthaw over a
      period of 42 days in culture and compare this profile to human fetal and adult as
      well as adult cynomolgus nonhuman primate (NHP, Macaca fascicularis) heart
      tissue. Our results indicate that iCC express relevant cardiac markers such as
      ion channels (SCN5A, KCNJ2, CACNA1C, KCNQ1, and KCNH2), tissue-specific
      structural markers (MYH6, MYLPF, MYBPC3, DES, TNNT2, and TNNI3), and
      transcription factors (NKX2.5, GATA4, and GATA6) and lack the expression of stem
      cell markers (FOXD3, GBX2, NANOG, POU5F1, SOX2, and ZFP42). Furthermore, we
      performed a functional evaluation of contractility of the iCC and showed
      functional and pharmacological correlations with myocytes isolated from adult NHP
      hearts. These results suggest that stem cell-derived cardiocytes may represent a
      novel in vitro model to study human cardiac toxicity with potential ex vivo and
      in vivo translation.

PMID- 22982685
TI  - Speed change detection in foveal and peripheral vision.
AB  - Perception of constant motion has been extensively studied both psychophysically
      and physiologically, but the human ability to detect dynamic changes in motion,
      such as rapid speed changes, is only poorly characterized and understood. Yet,
      perception and representation of such dynamic changes is of strong behavioral
      relevance, as illustrated by their potential for attentional capture. In the
      present study, we measured and compared detection thresholds for instantaneous
      accelerations and decelerations of drifting Gabor patches at different retinal
      eccentricities. As a main result, we find that detection performance depends
      strongly on eccentricity. Under foveal viewing conditions, average thresholds
      were lower for accelerations than for decelerations. However, between 5 degrees 
      and 15 degrees  eccentricity, this relation is inverted, and deceleration
      detection becomes better than acceleration detection. Results of an additional
      experiment suggest that this can be explained by a fast eccentricity-dependent
      adaptation effect. Our findings are discussed with special emphasis on their
      relation to data from neurophysiological experiments.

PMID- 22982686
TI  - Influence of donor microbiota on the severity of experimental graft-versus-host
      disease.
AB  - The link between microbial flora and the shaping of immune responses is being
      increasingly appreciated, and recent data have uncovered a role for recipient
      microbiota in the severity of graft-versus-host disease (GVHD). The impact of
      donor microbiota on T cell-mediated alloresponses and GVHD is not known, however.
      Using multiple clinically relevant murine models, we analyzed the effect of donor
      microbiota on the severity of GVHD induced by T cells from specific pathogen-free
      and germ-free donors, and found that donor microbiota does not alter the
      expansion or differentiation of alloreactive T cells or the severity of GVHD.

PMID- 22982687
TI  - Putative genes mediating the effects of orexins in the posterior paraventricular
      thalamus on neuroendocrine and behavioral adaptations to repeated stress.
AB  - Exposure to repeated stress is often associated with psychopathology. However,
      our understanding of the underlying neural circuitry that regulates responses to
      repeated stress is limited. The posterior paraventricular thalamus (pPVT) is a
      brain region responsible for transmission of multimodal sensory information to
      limbic structures that regulate responses to both acute and repeated stress.
      Orexin-containing cells originating in the hypothalamus heavily innervate the
      pPVT. Our previous work has shown that activation of orexin1 receptors in the
      pPVT during repeated swim stress is important for facilitation of the
      hypothalamic-pituitary-adrenal (HPA) axis response to subsequent novel restraint.
      However, the genes responsible for these orexin-mediated adaptations to repeated
      stress are not known. Using a custom PCR array we examined the expression of 186
      specific mRNAs in the pPVT of animals exposed to repeated swim stress (4 days of
      15min swim/day) with or without direct pPVT microinfusion of the orexin1 receptor
      antagonist SB334867 prior to each daily swim stress. Tissue was collected the
      next morning under basal non stressed conditions. Repeated stress and/or orexin
      receptor blockade significantly altered expression of only 9 specific genes
      including growth factors (Vegfa, Bax and Mt3), G-protein coupled receptors
      (Adora2a, Grm2 and Crhr1), immune-related genes (Ptgs2 and Cx3cr1) and an
      epigenetic-related gene (Hdac5). These genes represent potential targets for
      further characterization of orexin-mediated adaptations to repeated stress in the
      pPVT.

PMID- 22982688
TI  - The role of peripheral inflammatory markers in dementia and Alzheimer's disease:
      a meta-analysis.
AB  - BACKGROUND: Studies that have investigated the association between markers of
      inflammation and risk of dementia are conflicting. Therefore, the researchers
      conducted a systematic review and meta-analysis of observational studies with the
      hypothesis that an increased level of peripheral proinflammatory markers would be
      associated with risk of all-cause dementia or Alzheimer's disease (AD). METHODS:
      The researchers conducted a literature search of observational studies indexed in
      the PubMed and PsycInfo databases. Selected studies included those with at least
      one peripheral inflammatory biomarker and its association with risk of all-cause
      dementia or AD. Random effects models were used to generate pooled hazard ratios
      (HRs) comparing the top versus bottom quantile of inflammatory marker level.
      Heterogeneity was assessed using the I (2) statistic. RESULTS: Seven studies were
      identified, combining for a total 5,717 participants, 746 cases of all-cause
      dementia and 565 cases of AD. An increased level of C-reactive protein was
      associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI:
      1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32%
      increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD
      alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95%
      CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06;
      95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta
      analyses (I (2) = 0%-40%, p >= .16). CONCLUSIONS: An increased peripheral level
      of inflammatory markers is associated with a modest increase in risk of all-cause
      dementia. Evidence for an association with risk of AD alone is limited.

PMID- 22982689
TI  - Cognitive effects of reducing anticholinergic drug burden in a frail elderly
      population: a randomized controlled trial.
AB  - BACKGROUND: Observational studies report a relationship between anticholinergic
      drug scale (ADS) score and cognitive function. This study investigated whether a
      reduced ADS score improved cognitive function in a frail elderly population.
      METHODS: This randomized, controlled, single-blinded trial, recruited long-term
      residents with an ADS score of greater than or equal to 3 from 22 nursing homes
      in Norway. The participants were randomly allocated (1:1) to intervention or
      control. The intervention was a pharmacist-initiated reduction of ADS score after
      multidisciplinary drug reviews. Primary end point was Consortium to Establish a
      Registry for Alzheimer's Disease 10-wordlist test for immediate recall. Secondary
      end points were Mini-Mental Sate Examination, delayed recall and recognition of
      words, saliva flow, and serum anticholinergic activity (SAA).The participants
      were retested after 4 and 8 weeks, and the study groups were compared after
      adjusting for baseline differences. RESULTS: Eighty-seven patients were included.
      The median ADS score was reduced by 2 units (p < .0001) in the intervention group
      and remained unchanged in the control group. After 8 weeks, the adjusted mean
      difference in immediate recall was 0.54 words between the intervention and
      control group (95% confidence interval [CI]: -0.91, 2.05; p = .48). The study
      groups did not differ significantly in any of the other cognitive end points,
      salvia flow, or SAA at either follow-up (p > .18). CONCLUSION: Pharmacist
      initiated drug changes significantly reduced ADS score but did not improve
      cognitive function in nursing home residents. Moreover, the drug changes did not
      reduce SAA or mouth dryness significantly, which might indicate limited
      applicability of the ADS score to prevent prescription risks in this population.

PMID- 22982691
TI  - [Diabetic foot: definitions].
AB  - Diabetes is a metabolic disorder characterized by chronic hyperglycemia
      associated with impaired glucose, lipid and protein metabolism. The purpose of
      our work is to provide a clear and precise definition of the disease and of his
      frequent complications: diabetic foot and diabetic foot infection.

PMID- 22982690
TI  - A population-based examination of the visual and ophthalmological characteristics
      of licensed drivers aged 70 and older.
AB  - BACKGROUND: Safe driving performance depends on visual skills yet little is known
      about the prevalence of vision impairments in older drivers and the eye
      conditions that cause them. This study is a population-based examination of the
      prevalence of vision impairment and major ophthalmological conditions among
      drivers aged 70 and older. METHODS: The source population was a random sample of
      2,000 licensed drivers aged 70 and older residing in north central Alabama. All
      had driven within the past 3 months. Binocular visual acuity and contrast
      sensitivity were assessed. The Useful Field of View subtest 2 and Trails B
      assessed visual processing speed. Ophthalmological diagnoses for cataract,
      intraocular lens placement, glaucoma, diabetic retinopathy, age-related macular
      degeneration, and diabetic retinopathy were obtained through medical records from
      the most recent eye examination. RESULTS: Ninety-two percent of drivers had
      visual acuity of 20/40 or better; only two drivers (0.1%) had acuity worse than
      20/100. Ninety-three percent had normal contrast sensitivity (>=1.5). About 40%
      had slowed visual processing speed (44%, Useful Field of View; 38%, Trails B).
      The most common eye condition was cataract, with more than half having cataract
      in one or both eyes (56%); yet by the 80s and 90s, the prevalence was low, with
      most drivers having undergone cataract surgery and intraocular lens placement.
      CONCLUSIONS: This population-based study suggests that serious impairment in
      central vision-visual acuity or contrast sensitivity-is rather uncommon in older
      drivers; however, slowed visual processing speed is common.

PMID- 22982692
TI  - [Epidemiology of diabetic foot].
AB  - Diabetes is one of the most common diseases and, in many developing and newly
      industrialized countries, the epidemic is growing at a dizzying rate. The main
      problems for diabetics are related to chronic complications of the disease. Among
      the complications of diabetes, the diabetic foot is gaining a new importance
      because it implies for diabetics the highest number of hospital admissions and
      considerable costs. In fact, about 15% of diabetics will experience in their life
      a foot ulcer. The greatest risk for these patients is the amputation. According
      to several studies, about 25-50% of diabetic patients receive immediate
      amputation at the time of the first visit due to the infection. Overall, it is
      estimated that approximately 50-70% of all lower limb amputations are due to
      diabetes. Therefore, diabetes is the leading cause of non-traumatic amputation of
      the lower limb in western countries, with a risk in diabetic patients 15 times
      higher than non-diabetics.

PMID- 22982693
TI  - [Infected lesions of diabetic foot].
AB  - The diabetic foot lesions are the result of a complex set of factors including
      peripheral neuropathy, trauma, joint deformities and perfusion abnormalities. The
      foot becomes vulnerable and insensitive to minor injuries caused by excessive
      pressure, mechanically or minimum thermal insults that can determine the primum
      movens of a foot ulcer. Due to the trauma, the subcutaneous tissues are exposed
      to bacterial colonization. Therefore, the wound can develop an infection. So, the
      first step in the treatment of the lesion is the evaluation of tissue damage, in
      order to guide therapy and prognosis. Wagner's classification, used by over 25
      years, is still one of the best known systems of lesion classification; however,
      it is giving way to the most recent Texas's classification. However, in both
      systems infection have a minority role. Therefore, the Infectious Diseases
      Society of America has developed a classification system that divides infections
      in mild, moderate and severe. The purpose of this classification is to recognize
      the severe patients because they require immediate hospitalization, parenteral
      antibiotic therapy and specific instrumental examinations.

PMID- 22982694
TI  - [Diabetic foot infections: microbiological aspects].
AB  - The diagnosis of wound infection is based on clinical signs and local and/or
      systemic inflammation. Therefore, the examination has a major role in the
      diagnosis of infected lesions of the foot. Once the clinical diagnosis of
      infection is made, the next step is to determine the etiology with the aim to
      undertake a rational and appropriate treatment. The most reliable method for
      assessing microbiological etiology is the specimen of material from infected
      lesion to perform a bacterioscopic examination and culture. The microorganisms
      involved in the etiology of diabetic foot depends on the type of injury and on
      specific patient features (antibiotic therapy, previous hospitalization). The
      most frequently detected pathogen is Staphylococcus aureus. Mild infections are
      mostly caused by Gram positive cocci, with a prevalence of S. aureus. Moderate
      infections are mostly supported by pyogenic Gram positive cocci, but also Gram
      negative bacteria can be involved. In severe infections the etiology is
      polymicrobial. As regards the involvement of fungi in diabetic foot infections
      data are few and mostly conflicting.

PMID- 22982695
TI  - [Management of diabetic foot infections].
AB  - All infected diabetic foot wounds require antibiotic treatment. Antibiotic
      treatment is influenced by the patient's features as the vascular status, the
      leukocyte function and the kidney activity. The initial antibiotic regimen is
      usually chosen empirically and it can be modified on the basis of the
      microbiological information obtained subsequently. The initial empiric therapy
      should be based, on one hand, on the grade of infected lesion and, secondly, on
      the epidemiological data. Almost all of the mild/moderate infected wounds can be
      treated with antibiotics with a spectrum of activity limited to Gram-positive
      cocci. Treatment with oral antibiotics is sufficient in most cases in patients
      with mild/moderate infections. With severe infections is more appropriate to use
      a broad-spectrum antibiotic therapy. Furthermore it is safer to start a
      parenteral therapy, possibly modifying it into an oral administration if the
      patient has stabilized. The most frequently pathogen observed in diabetic foot
      infections is Staphylococcus aureus. It is important to understand whether there
      are elements that may lead to the suspicion of MRSA infection in order to
      establish an appropriate antimicrobial therapy.

PMID- 22982696
TI  - [Adjuvant treatment of diabetic foot].
AB  - A diabetic infected foot with erythema and fluctuation can suspect that the
      infection has passed the fascial compartmental, a condition that requires
      surgical drainage. Elective amputation may be considered for patients who have
      recurrent ulcers, irreversible loss of function or injuries that require long
      term treatment in the hospital. If the diabetic infected foot appears ischemic it
      requires a treatment of revascularization. The outcome of revascularization is
      related with the extension of the damaged artery. The debridement removes the
      bacterial colonies, promotes granulation tissue and its reepithelialization, also
      facilitates the collection of samples for microbiological analyses. This
      procedure can be performed with the classic sharp instruments or with advanced
      autolytic dressings, maggots or ultrasonic equipment. The use of hyperbaric
      oxygen therapy in the treatment of infected diabetic foot is controversial
      because studies in this area are few and methodologically questionable. The same
      conclusion was reached also for the use of growth factors and skin substitutes.

PMID- 22982697
TI  - Implementation of a knowledge-based methodology in a decision support system for
      the design of suitable wastewater treatment process flow diagrams.
AB  - In light of rapid global change, the demand for wastewater treatment is
      increasing rapidly and will continue to do so in the near future. Wastewater
      management is a complex puzzle for which the proper pieces must be combined to
      achieve the desired solution, requiring the simultaneous consideration of
      technical, economic, social and environmental issues. In this context, a
      knowledge-based methodology (KBM) for the conceptual design of wastewater
      treatment plant (WWTP) process flow diagrams (PFDs) and its application for two
      scenarios is presented in this paper. The core of the KBM is composed of two
      knowledge bases (KBs). The first, a specification knowledge base (S-KB),
      summarizes the main features of the different treatment technologies: pollutants
      removal efficiency, operational costs and technical reliability. The second, a
      compatibility knowledge base (C-KB), contains information about the different
      interactions amongst the treatment technologies and determines their degree of
      compatibility. The proposed methodology is based on a decision hierarchy that
      uses the information contained in both KBs to generate all possible WWTP
      configurations, screening and selecting appropriate configurations based on user
      specified requirements and scenario characteristics. The design of the most
      adequate treatment train for small and medium sized wastewater treatment plants
      (2000 and 50,000 p.e. respectively) according to different restrictions (space
      constraints, operation simplicity and cost optimization) was the example in order
      to show the usefulness of the KBM.

PMID- 22982698
TI  - [First case report of catheter-related fungemia by Candida nivariensis in the
      Iberian Peninsula].
AB  - BACKGROUND: In recent years the incidence of candidemia caused by non-albicans
      Candida species has been increasing. Two cryptic species have been described
      within the Candida glabrata complex, Candida nivariensis and Candida bracarensis,
      which may be troublesome in laboratory identification and have lower
      susceptibility to fluconazole. AIMS: To describe the first isolation of C.
      nivariensis in the Iberian Peninsula from a patient suffering from a catheter
      related fungemia. CASE REPORT: An 81-year-old man was hospitalized for surgical
      treatment of an intestinal fistula that was associated to a severe malnutrition.
      Cultures of the patient's central venous catheter tip and blood yielded white
      colonies in BD CHROMagar Candida((r)) medium, which could not be identified by
      conventional microbiological methods. Although intravenous fluconazole was
      administered, blood cultures continued being positive 5 days later. The MIC
      values of the isolate were as follows: 1 MUg/ml for amphotericin B, 0.015 MUg/ml
      for anidulafungin, 0.125 MUg/ml for caspofungin, 0.015 MUg/ml for micafungin, 4
      MUg/ml for fluconazole, 0.25 MUg/ml for itraconazole, 0.25 MUg/ml for
      posaconazole, and 0.03 MUg/ml for voriconazole. Antifungal treatment was changed
      to intravenous caspofungin for 2 weeks. The intestinal fistula was surgically
      treated. There was no evidence of relapse during the following month, and the
      patient was discharged. The isolate was identified as C. nivariensis based on DNA
      sequencing of the ITS regions of rRNA. CONCLUSIONS: C. nivariensis should be
      regarded as an emerging pathogen which requires molecular methods for a
      definitive identification. Our patient was successfully treated with caspofungin.

PMID- 22982699
TI  - Translating policies into practice: a framework to prevent childhood obesity in
      afterschool programs.
AB  - Afterschool programs (3-6 p.m.) are positioned to play a critical role in
      combating childhood obesity. To this end, state and national organizations have
      developed policies related to promoting physical activity and guiding the
      nutritional quality of snacks served in afterschool programs. No conceptual
      frameworks, however, are available that describe the process of how afterschool
      programs will translate such policies into daily practice to reach eventual
      outcomes. Drawing from complex systems theory, this article describes the
      development of a framework that identifies critical modifiable levers within
      afterschool programs that can be altered and/or strengthened to reach policy
      goals. These include the policy environment at the national, state, and local
      levels; individual site, afterschool program leader, staff, and child
      characteristics; and existing outside organizational partnerships. Use of this
      framework and recognition of its constituent elements have the potential to lead
      to the successful and sustainable adoption and implementation of physical
      activity and nutrition policies in afterschool programs nationwide.

PMID- 22982700
TI  - Identifying health promotion needs among prison staff in three English prisons:
      results from a qualitative study.
AB  - Prisons are seen as a (temporary) home and community for offenders, yet they also
      have a dual role as a workplace for prison staff. This article explores how the
      "healthy settings" philosophy, commonly used in schools, applies in the prison
      environment. The article explores the concept of the health-promoting prison from
      the perspective of prison staff using semistructured interviews in three English
      prisons. Data were analyzed using Attride-Stirling's thematic network approach.
      The findings indicate that working in a prison can be highly stressful and can
      have a negative impact on physical and mental health. Staff perceived that the
      focus of health promotion efforts was in many cases exclusively focused on
      prisoners, and many suggested that prison staff needs were being overlooked. The
      article argues that the theory and practice of a health-promoting prison have
      developed rapidly in recent years but still lag behind developments in other
      organizations. The article suggests that health promotion policy and practice in
      prison settings may need to be reconfigured to ensure that the needs of all those
      who live and work there are recognized.

PMID- 22982702
TI  - Addressing the information gap: developing and implementing a cervical cancer
      prevention education campaign grounded in principles of community-based
      participatory action.
AB  - Despite significant advances in prevention, Mexican American women continue to
      experience disparities related to cervical cancer and access to current and
      relevant health information. To address this disparity a community-campus
      partnership initiated an outreach program to Latinas in Arizona as one part of an
      integrated approach. Promotoras (community health workers) provided the
      leadership in the development of a curriculum to (a) train promotoras on cervical
      cancer, (b) meet informational needs of community members, (c) address relevant
      social determinants of heath, and (d) promote access to health care. The purpose
      of this article is to describe the community-based participatory approach used in
      the development of the curriculum. Specifically, the article describes the
      leadership of promotoras, the curriculum development, and the use of continual
      feedback to inform the quality control. To address cervical cancer disparities
      for Mexican American women, the Pima County Cervical Cancer Prevention
      Partnership used principles of community-based participatory action.

PMID- 22982703
TI  - Lessons learned from exploratory research about viral hepatitis.
AB  - The Centers for Disease Control and Prevention conducted exploratory research as
      part of planning a national education campaign to raise awareness about viral
      hepatitis in the United States. The purpose of this qualitative research was to
      assess the baseline knowledge, attitudes, and screening behaviors of four
      population groups. Sixteen focus groups were conducted during a 6-week period in
      the fall of 2009, with a total of 119 adults aged 35 to 60 years in Boston,
      Massachusetts; Chicago, Illinois; and Houston, Texas. The groups were stratified
      by Asian Americans, African Americans, gay or bisexual men, and general
      population. Group size ranged from three to nine participants, and each session
      was approximately 90 minutes in length. Both awareness and knowledge of viral
      hepatitis were low among all participants, including those at increased risk for
      the disease. Little was known about the different types of hepatitis, risk
      factors, or how the viruses are transmitted. Regarding the last, many indicated
      that the disease was airborne. In addition, participants incorrectly assumed that
      if they had viral hepatitis, they would have symptoms and know they were
      infected. Many participants also believed that they had been tested for the
      disease since their health care providers routinely "test their blood." The
      findings indicate that significant and concerted educational efforts are needed
      to improve basic knowledge of viral hepatitis, as well as knowledge about
      transmission, risk factors, screening, and treatment. As a result, a general
      awareness and education campaign must precede and support efforts to encourage
      screening.

PMID- 22982704
TI  - Evaluation framework for translational research: case study of Australia's get
      healthy information and coaching service(R).
AB  - The Get Healthy Information and Coaching Service(r) (GHS), a free government
      funded telephone-delivered information and coaching service was launched in
      February 2009 by the Australian New South Wales state government. It represents
      the translation of research evidence applied in the real world (T4 or Phase 4
      translation), aimed at addressing the modifiable risk factors associated with the
      overweight and obesity. In controlled settings, it has been established that
      telephone-based lifestyle counseling programs are efficacious in reducing
      anthropometric and behavioral risk factors. This article presents the GHS case
      study as a population-wide intervention and describes the quasi-experimental
      evaluation framework used to evaluate both the process (statewide implementation)
      and impact (effectiveness) of the GHS in a real-world environment. It details the
      data collection, measures, and statistical analysis required in assessing the
      process of implementation-reach and recruitment, marketing and promotion, service
      satisfaction, intervention fidelity, and GHS setting up and operations costs-and
      in assessing the impact of GHS-increasing physical activity, improving dietary
      practices, and reducing body weight and waist circumference. The comprehensive
      evaluation framework designed for the GHS provides a method for building
      effectiveness evidence of a rare translation of efficacy trial evidence into
      population-wide practice.

PMID- 22982705
TI  - A toolkit to promote fidelity to health promotion interventions in afterschool
      programs.
AB  - Community-based obesity prevention efforts are an essential component of a public
      health approach to obesity and chronic disease risk reduction. Afterschool
      programs can participate by providing healthy snacks and regular physical
      activity. Although efficacious obesity prevention strategies have been
      identified, they have not been widely implemented. The authors describe the
      development of A+, a quality improvement (QI) toolkit designed to help YMCA
      afterschool programs implement healthy eating and physical activity guidelines.
      YMCA of the USA Health Promotion Standards for afterschool sites specify
      eliminating sugar-sweetened beverages and trans fats; providing fruits,
      vegetables, and water; and ensuring at least 30 minutes of physical activity
      daily. Field tests of A+ indicated that a QI toolkit for community-based
      afterschool programs can be implemented by a program director across multiple
      program sites, responds to programmatic needs, appropriately identifies barriers
      to improvement, and permits development of locally appropriate improvement plans.
      The QI approach holds promise for public health efforts and for field research to
      evaluate promising interventions by helping ensure full implementation of health
      promotion strategies.

PMID- 22982706
TI  - Dissemination of colorectal cancer screening by Filipino American community
      health advisors: a feasibility study.
AB  - BACKGROUND: Filipino Americans underutilize life-saving screening tests for
      colorectal cancer, resulting in late stage of diagnosis and poor survival
      relative to other racial/ethnic groups. Education regarding colorectal cancer
      screening and distribution of free fecal occult blood test (FOBT) kits are
      evidence-based interventions that can significantly increase screening. However,
      this community will only benefit if the intervention is broadly disseminated.
      METHODS: We assessed the feasibility of promoting colorectal cancer screening in
      Filipino American community settings working with community health advisors, and
      the practicality of conducting one-on-one or small group education, in addition
      to passing out free FOBT kits. RESULTS: Twenty community health advisors from 4
      organizations engaged in recruitment and education activities with 132
      participants. Community health advisors consistently completed screening
      questionnaires to establish eligibility and kept logs of FOBT distribution.
      However, they did not consistently record eligible participants who did not
      consent to participate. Process checklists that indicated what information was
      covered in each educational session and postsession follow-up logs were partially
      completed. Almost all participants reported receipt of intervention components
      and receipt of screening at 4-month follow-up and reported high acceptability of
      the program. DISCUSSION: The pilot study established the feasibility of working
      with community health advisors to promote colorectal cancer screening in Filipino
      American community settings. Findings informed the design of a dissemination
      trial that is currently ongoing with regards to monitoring recruitment,
      intervention implementation and follow-up and allowing flexibility regarding one
      on-one or small group education.

PMID- 22982707
TI  - Integrating health literacy and ESL: an interdisciplinary curriculum for Hispanic
      immigrants.
AB  - Adult Hispanic immigrants are at a greater risk of experiencing the negative
      outcomes related to low health literacy, as they confront cultural and language
      barriers to the complex and predominately monolingual English-based U.S. health
      system. One approach that has the potential for simultaneously addressing the
      health, literacy, and language needs of Hispanics is the combination of health
      literacy and English as a second language (ESL) instruction. The purpose of the
      project was to evaluate the feasibility of using ESL instruction as a medium for
      improving health literacy among Hispanic immigrants. Objectives included the
      development, implementation, and evaluation of an interdisciplinary health
      literacy/ESL curriculum that integrates theories of health literacy and health
      behavior research and practice, sociocultural theories of literacy and
      communication, and adult learning principles. This article describes the
      curriculum development process and provides preliminary qualitative data on
      learners' experiences with the curriculum. Results indicate that the curriculum
      was attractive to participants and that they were highly satisfied with both the
      format and content. The curriculum described here represents one example of an
      audience-centered approach designed to meet the specific health and literacy
      needs of the Hispanic population on the U.S.-Mexico border. The combination of
      ESL and health literacy contributed to a perceived positive learning experience
      among participants. Interdisciplinary approaches to health literacy are
      recommended.

PMID- 22982708
TI  - The relationship between local public health agency characteristics and
      performance of partnership-related essential public health services.
AB  - OBJECTIVE: The relationships between characteristics of local public health
      agencies and their self-reported scores on partnership-related indicators of the
      Ten Essential Public Health Services were examined. DESIGN: A retrospective cross
      sectional study using secondary data from the National Public Health Performance
      Standards Program (NPHPSP) and the 2005 Profile of Local Public Health Agencies
      from the National Association of City and County Health Organizations (NACCHO)
      was completed. Participants. Local public health systems that participated in
      both the NPHPSP and the NACCHO surveys. MAIN OUTCOME MEASURES: Partnership
      related elements from the NPHPSP data set were used as dependent variables,
      whereas combined focused elements from the NPHPSP and the NACCHO surveys served
      as independent variables. RESULTS: Local public health agencies' increase in
      partnerships over the preceding 3 years and involvement in a community health
      improvement process were significantly related to numerous partnership
      performance scores--more so than other agency characteristics. Involvement in the
      Mobilizing Action through Planning and Partnerships process was inversely related
      to some partnership performance scores. CONCLUSIONS: Future research must
      continue to identify and explore additional community- and agency-level
      predictors of partnership performance.

PMID- 22982709
TI  - Designing a community-based lay health advisor training curriculum to address
      cancer health disparities.
AB  - INTRODUCTION: Racial and ethnic minorities have disproportionately higher cancer
      incidence and mortality than their White counterparts. In response to this
      inequity in cancer prevention and care, community-based lay health advisors
      (LHAs) may be suited to deliver effective, culturally relevant, quality cancer
      education, prevention/screening, and early detection services for underserved
      populations. APPROACH AND STRATEGIES: Consistent with key tenets of community
      based participatory research (CBPR), this project engaged community partners to
      develop and implement a unique LHA training curriculum to address cancer health
      disparities among medically underserved communities in a tricounty area. Seven
      phases of curriculum development went into designing a final seven-module LHA
      curriculum. In keeping with principles of CBPR and community engagement, academic
      community partners and LHAs themselves were involved at all phases to ensure the
      needs of academic and community partners were mutually addressed in development
      and implementation of the LHA program. DISCUSSION AND CONCLUSIONS: Community
      based LHA programs for outreach, education, and promotion of cancer screening and
      early detection, are ideal for addressing cancer health disparities in access and
      quality care. When community-based LHAs are appropriately recruited, trained, and
      located in communities, they provide unique opportunities to link, bridge, and
      facilitate quality cancer education, services, and research.

PMID- 22982710
TI  - Dielectric properties of porcine glands, gonads and body fluids.
AB  - Dielectric properties of porcine glandular tissues and gonads (in vivo) and body
      fluids (in vitro) have been obtained in the frequency range of 50 MHz to 20 GHz.
      The experimental data were fitted to a two term Cole-Cole expression. The data
      presented complement the available dielectric properties of tissues in the
      literature and can be used in numerical simulations of the exposure of people to
      electromagnetic fields.

PMID- 22982712
TI  - Blood flow restriction: an evidence based progressive model (Review).
AB  - To remain independent and healthy, an important factor to consider is the
      maintenance of skeletal muscle mass. Inactivity leads to measurable changes in
      muscle and bone, reduces exercise capacity, impairs the immune system, and
      decreases the sensitivity to insulin. Therefore, maintaining physical activity is
      of great importance for skeletal muscle health. One form of structured physical
      activity is resistance training. Generally speaking, one needs to lift weights at
      approximately 70% of their one repetition maximum (1RM) to have noticeable
      increases in muscle size and strength. Although numerous positive effects are
      observed from heavy resistance training, some at risk populations (e.g. elderly,
      rehabilitating patients, etc.) might be advised not to perform high-load
      resistance training and may be limited to performance of low-load resistance
      exercise. A technique which applies pressure cuffs to the limbs causing blood
      flow restriction (BFR) has been shown to attenuate atrophy and when combined with
      low intensity exercise has resulted in an increase in both muscle size and
      strength across different age groups. We have provided an evidence based model of
      progression from bed rest to higher load resistance training, based largely on
      BFR literature concentrating on more at risk populations, to highlight a possible
      path to recovery.

PMID- 22982711
TI  - Glutamate biosensor imaging reveals dysregulation of glutamatergic pathways in a
      model of developmental cortical malformation.
AB  - Cortical malformations can cause intractable epilepsy, but the underlying
      epileptogenic mechanisms are poorly understood. We used high-speed glutamate
      biosensor imaging to ask how glutamatergic signaling is altered in cortical
      malformations induced by neonatal freeze-lesions (FL). In non-lesion neocortical
      slices from 2 to 8week old rats, evoked glutamate signals were symmetrical in the
      medio-lateral axis and monotonic, correlating with simple, brief (~50ms) local
      field potentials (LFPs). By contrast, in FL cortex glutamate signals were
      prolonged, increased in amplitude, and polyphasic, which paralleled a
      prolongation of the LFP. Using glutamate biosensor imaging, we found that
      glutamate signals propagated throughout large areas of FL cortex and were
      asymmetric (skewed toward the lesion). Laminar analysis demonstrated a shift in
      the region of maximal glutamate release toward superficial layers in FL cortex.
      The ability to remove exogenous glutamate was increased within the FL itself but
      was decreased in immediately adjacent regions. There were corresponding
      alterations in astrocyte density, with an increase within the lesion and a
      decrease in deep cortical layers surrounding the lesion. These findings
      demonstrate both network connectivity and glutamate metabolism are altered in
      this cortical malformation model and suggests that the regional ability of
      astrocytes to remove released glutamate may be inversely related to local
      excitability. 

PMID- 22982713
TI  - Effect of arterial carbon dioxide on ventilation during recovery from impulse
      exercises of various intensities.
AB  - To determine that whether arterial carbon dioxide (PaCO2) affects ventilation
      (VE) during recovery from impulse-like exercises of various intensities, subjects
      performed four impulse-like tests with different workloads. Each test consisted
      of a 20-sec impulse-like exercise at 80 rpm and 60-min recovery. Blood samples
      were collected at rest and during recovery to measure blood ions and gases. VE
      was measured continuously during rest, exercise and recovery periods. A
      significant curvilinear relationship was observed between VE and pH during
      recovery from the 300- and 400-watt tests in all subjects. VE was elevated during
      recovery from the 100-watt test despite no change in any of the humoral factors.
      Arterialized carbon dioxide (PaCO2) kinetics showed fluctuation, being increased
      at 1 min and decreased at 5 min during recovery, and this fluctuation was more
      enhanced with increase in exercise intensity. There was a significant
      relationship between VE and PaCO2 during recovery from the 300- and 400-watt
      tests in all subjects. The results of the present study demonstrate that pH and
      neural factors drive VE during recovery from impulse-like exercise and that
      fluctuation in PaCO2 controls VE as a feedback loop and this feedback function is
      more enhanced as the work intensity increases.

PMID- 22982714
TI  - The impact of water-floating and high-intensity exercise on rat's HPA axis and
      interleukins concentrations.
AB  - Our studies explore the changes of blood corticosterone (CORT),
      adrenocorticotropic hormone (ACTH), interleukin (IL)-1beta, IL-2, IL-6
      concentrations and the pituitary ACTH expression in rats after water floating in
      the presence or absence of following high-intensity exercise. The rats were
      randomly assigned into three groups. Group A served as control; Group B received
      180 minutes water floating and psychological (fear) stimulation; Group C received
      the same treatment as Group B in addition and 120-minutes non-stop running.
      Compared to Group A, Group B showed a significant increase of IL-2 (19.91 +/-
      2.52 vs. 13.09 +/- 3.13 ng/ml, P < 0.05), and IL-6 (0.18 +/- 0.08 vs. 0.12 +/-
      0.05 ng/ml, P < 0.05); Group C demonstrated a significant increase of CORT
      (977.22 +/- 207.36 ng/ml vs. 434.58 +/- 110.45 ng/ml, P <0.01) and IL-1beta (0.21
      +/- 0.04 vs. 0.16 +/- 0.06 ng/ml, P < 0.05), IL-2 (20.29 +/- 4.23 vs. 13.09 +/-
      3.13 ng/ml, P < 0.05), and IL-6 (0.19 +/- 0.03 vs. 0.12 +/- 0.05 ng/ml, P < 0.05)
      levels, and a significant decrease of ACTH (16.95 +/- 5.46 vs. 22.96 +/- 7.32
      pg/ml, P = 0.03). Immunohistochemical staining showed the decreased number of
      pituitary ACTH-positive cells in both Groups B and C (P < 0.05) as compared to
      Group A. These results have lead us to believe that acute psychological stress
      can activate the pituitary-adrenal axis and lead to elevation of serum IL-2, IL-6
      concentrations. Combined with high-intensity exercise, it can result in the
      increase of serum CORT, IL-1beta, IL-2, IL-6 levels, and the suppression of ACTH.

PMID- 22982715
TI  - Does increased aortic stiffness predict reduced coronary flow velocity reserve in
      patients with suspected coronary artery disease?
AB  - PURPOSE: In recent studies, reduction in coronary flow velocity reserve (CFR) has
      been demonstrated in patients with increased aortic stiffness. Stress
      transoesophageal echocardiography (TEE) is a suitable method for the simultaneous
      evaluation of CFR and aortic stiffness parameters. The present study was designed
      to test whether increased echocardiography-derived aortic elastic modulus [E(p)]
      predicts impaired CFR in patients with suspected coronary artery disease (CAD).
      RESULTS: The present study comprised 158 patients with suspected CAD. A CFR value
      < 2 was considered abnormal. Both men grade of aortic atherosclerosis (AA) (as a
      morphologic characteristic) (1.31 +/- 0.68 vs. 1.02 +/- 0.89, p < 0.05) and
      aortic distensibility (E(p) as a functional characteristic) (892 +/- 594 mmHg vs.
      723 +/- 495 mmHg, P < 0.05) were increased in subjects with CFR < 2. In ROC
      analysis, the cut-off value for E(p) to predict impaired CFR was >= 670 mmHg,
      with 61% sensitivity and 61% specificity (ROC area 0.60, p = 0.026). The logistic
      regression model identified higher AA grade (hazard ratio (HR) 2.01, p < 0.05)
      and increased E(p) as independent predictors of reduced CFR (HE 1.10, p < 0.05).
      CONCLUSION: Increased aortic stiffness predicts impaired CFR in patients with
      suspected CAD.

PMID- 22982716
TI  - Arteriolar biomechanics in a rat polycystic ovary syndrome model - effects of
      parallel vitamin D3 treatment.
AB  - To clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary
      syndrome (PCOS) on arteriolar biomechanics in a rat model and the possible
      modulatory role of vitamin D3. METHODS AND RESULTS: The PCOS model was induced in
      female Wistar rats by ten-weeks DHT treatment. Arteriolar biomechanics was tested
      in arterioles by pressure arteriography in control as well as DHT- and DHT with
      vitamin D3-treated animals in contracted and passive conditions. Increased wall
      stress and distensibility as well as increased vascular lumen were detected after
      DHT treatment. Concomitant vitamin D3 treatment lowered the mechanical load of
      the arterioles and restored the vascular diameter. CONCLUSION: The
      hyperandrogenic state resulted in more rigid, less flexible arteriolar walls with
      increased vascular lumen compared with controls. DHT treatment caused eutrophic
      remodelling of gracilis arteriole. These prehypertensive alterations caused by
      chronic DHT treatment were mostly reversed by concomitant vitamin D3
      administration.

PMID- 22982717
TI  - Pulmonary mechanical responses to intestinal ischaemia-reperfusion and endotoxin
      preconditioning.
AB  - During intestinal ischaemia-reperfusion, endotoxin can be translocated.
      Pretreatment with sublethal doses of endotoxin develops tolerance to ischaemia
      reperfusion in different organs; however, the tolerance to intestinal ischaemia
      reperfusion in the lung has rarely been investigated. Our aim was to study the
      role of endotoxin pretreatment in the mechanical responses and inflammatory
      activation induced by intestinal ischaemia-reperfusion in the lung. Wistar rats
      were preconditioned with a sublethal dose of endotoxin on day -3 or -1. On day 0,
      anesthetized, paralyzed and mechanically ventilated rats were subjected to a 60
      min occlusion of the superior mesenteric artery and a subsequent 240-min
      reperfusion. The low-frequency forced oscillation technique was employed to
      characterize the separate mechanical responses of the airways and respiratory
      tissues. Intestinal ischaemia-reperfusion caused a significant decrease in airway
      resistance and increases in tissue resistance and elastance, nitric oxide
      synthase and myeloperoxidase activities. Pretreatment with endotoxin modified
      both the pulmonary mechanical responses and the inflammatory markers in the lung
      during intestinal ischaemia-reperfusion. We conclude that endotoxin or the
      endotoxin-induced processes (and humoral mediators) have significant roles in the
      pathomechanism of the remote pulmonary effect of intestinal ischaemia
      reperfusion.

PMID- 22982718
TI  - Relation of circulating T cell profiles to airway inflammation and asthma control
      in asthmatic pregnancy.
AB  - Asthmatic inflammation during pregnancy poses a risk for maternal and fetal
      morbidities. Circulating T cell immune phenotype is known to correlate with
      airway inflammation (detectable by fractional concentration of nitric oxide
      present in exhaled breath (FENO)) in non-pregnant allergic asthmatics. The aim of
      this study was to assess the relationship of peripheral T cell phenotype to FENO
      and clinical variables of asthma during pregnancy.We examined 22 pregnant women
      with allergic asthma in the 2nd/3rd trimester. The prevalence of Th1, Th2,
      regulatory T (Treg) and natural killer (NK) cell subsets was identified with flow
      cytometry using cell-specific markers. FENO, Asthma Control Test (ACT) total
      score and lung function were evaluated.Peripheral blood Th1, Th2, Treg, and NK
      cell prevalence were not significantly correlated to airway inflammation assessed
      by FENO in asthmatic pregnant women (all cells p > 0.05; study power > 75%).
      However, an inverse correlation was detected between Th2 cell prevalence and ACT
      total scores (p = 0.03) in asthmatic pregnancy.Blunted relationship between T
      cell profile and airway inflammation may be the result of pregnancy induced
      immune tolerance in asthmatic pregnancy. On the other hand, increased Th2
      response impairs disease control that supports direct relationship between
      symptoms and cellular mechanisms of asthma during pregnancy.

PMID- 22982719
TI  - Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons
      during hypoxia/ischemia.
AB  - Berberine, a primary pharmacological active constitute of Coptidis Rhizoma, could
      inhibit neuronal apoptosis in cerebral ischemia. Here, we aimed to investigate
      whether and how HIF-1 is implicated in the anti-apoptosis effect of berberine on
      neurons under hypoxia/ischemia. Viability of PC12 cells treated with berberine
      prior to or following CoCl2-induced hypoxia was evaluated. Annexin V-PI staining
      was employed to analyse cell apoptosis ratio. HIF-1alpha and apoptosis-associated
      molecules were detected via Western blotting. TUNEL and immunohistochemistry were
      used to demonstrate apoptosis, HIF-1alpha and p53 levels in cerebral tissue of
      middle cerebral artery occlusion (MCAO) rats. Berberine pretreatment promoted
      PC12 cells survival and inhibited apoptosis under hypoxia condition. At the same
      time, it decreased cell viability and enhancement of apoptosis were observed with
      berberine treatment under hypoxia. Decreased HIF-1alpha, caspase 9, caspase 3 and
      increased Bcl-2/Bax ratio were responsible for the anti-apoptosis of berberine
      pretreatment. However, pro-apoptosis by berberine under hypoxia was indicated
      with opposing regulation of those molecules. Significant reduction of apoptosis,
      HIF-1alpha and p53 were found in cerebral tissue of MCAO rats treated with
      berberine. The present study suggests that berberine regulates neuronal apoptosis
      in cerebral ischemia, which might be dependent on the degree of cell injury. HIF
      1 and the followed apoptotic pathway are involved in those effects of berberine.

PMID- 22982720
TI  - Comparative study of PEP mask and Flutter on expectoration in cystic fibrosis
      patients.
AB  - The objective of the study was to investigate the effect of positive expiratory
      pressure (PEP) and Flutter on expectoration in cystic fibrosis (CF) patients.
      Data was gathered through 260 treatments with 10 patients (5 female; 19.2 years;
      BMI: 18.0). Two methods were used alternately, first the patients started with
      Flutter and proceeded with PEP, and the next occasion they exercised in the
      reverse order, starting with PEP then continuing with Flutter. During each phase,
      5 sets of 10 exhalations were performed. Sputum weight was measured after the use
      of the first device, and at the end of the treatment. During sessions starting
      with Flutter 4.0 +/- 4.0 g sputum was expectorated, continuing with PEP, an
      additional 5.2 +/- 5.0 g was produced, altogether 9.2 +/- 8.2 g. At sessions
      starting with PEP 7.4 +/- 3.7 g was expectorated, continuing with Flutter an
      additional 0.8 +/- 1.4 g, that is 8.2 +/- 4.1 g. Comparing the two devices by
      themselves, PEP proved to be significantly more efficient then Flutter. Comparing
      the two treatment types it is statistically not proven, which one is preferable
      using both devices. Conclusively, PEP is significantly more efficient than the
      Flutter in sputum expectoration among CF patients. The Flutter is a useful
      supplementary device.

PMID- 22982721
TI  - EEG effect of orexin A in freely moving rats.
AB  - Orexin A and orexin B are neuropeptides produced by a group of neurons located in
      the lateral hypothalamus which send widespread projections virtually to the whole
      neuraxis. Several studies indicated that orexins play a crucial role in the sleep
      wake regulation and in the pathomechanism of the sleep disorder narcolepsy. As no
      data are available related to the EEG effects of orexin A in healthy, freely
      moving rats, the aim of the present experiments was to analyze EEG power changes
      in the generally used frequency bands after intracerebroventricular orexin A
      administration.Orexin A administration (0.84 and 2.8 nM/rat) differently affected
      fronto-occipital EEG waves in the different frequency bands recorded for 24
      hours. Delta (1-4 Hz) and alpha (10-16 Hz) power decreased, while theta (4-10 Hz)
      and beta (16-48 Hz) power increased. Decrease of the delta power was followed by
      a rebound in case of the higher orexin A dose. This complex picture might be
      explained by the activation of several systems by the orexin A administration.
      Among these systems, cortical and thalamic circuits as well as the role of the
      neurons containing corticotrophin-releasing factor might be of significant
      importance.

PMID- 22982722
TI  - Organizer and regulatory role of colonic isolated lymphoid follicles in
      inflammation.
AB  - Gut-associated lymphoid tissue (GALT) is supposed to play an integral role in the
      organization of colonic repair mechanisms. Majority of the GALT is composed of
      isolated and aggregated lymphoid follicles distributed throughout the intestines.
      These lymphoid follicles, including Peyer's patches of the small, and isolated
      lymphoid follicles (ILFs) of both the small and large intestines, are composed of
      a specialised follicle associated epithelium overlying a subepithelial dome
      containing numerous dendritic cells, macrophages, T and B cells. Within
      inflammatory conditions the number, the diameter and the density of ILFs are
      increasing. Follicles are involved not just in immune surveillance, but their
      presence is also indispensable for normal colonic mucosal regeneration. Regarding
      mucosal repair the relation of ILFs to bone marrow derived stem cells, follicular
      dendritic cells, subepithelial myofibroblasts and crypt formations, and the
      putative organizer role of ILFs have not been clarified yet.

PMID- 22982723
TI  - Characterization of antinociceptive potency of endomorphin-2 derivatives with
      unnatural amino acids in rats.
AB  - This study reports on the in vivo effects of four endomorphin-2 (EM-2)
      derivatives (EMD1-4) containing unnatural amino acids, i.e. 2
      aminocyclohexanecarboxylic acid (Achc2), para-fluorophenylalanine (pFPhe4), beta
      methylphenylalanine (betaMePhe4) and/or 2',6'-dimethyltyrosine (Dmt1). After
      induction of osteoarthritis by monosodium iodoacetate into the ankle joint of
      male Wistar rats, a chronic intrathecal catheter was inserted for spinal drug
      delivery. The mechanical threshold was assessed by a dynamic aesthesiometer.
      Intrathecal injection of the original EM-2 and the ligands (0.3-10 MUg) caused
      dose-dependent antiallodynic effects. The comparison of the different substances
      revealed that EMD3 and EMD4 showed more prolonged antinociception than EM-2, and
      the effects of the highest dose of EMD4 were comparable to morphine, while EMD3
      caused paralysis at this dose. The potency of the different ligands did not
      differ from EM-2. The results show that the derivatives of EM-2 have similar in
      vivo potency to the original ligand, but their effects were more prolonged
      suggesting that these structural modifications may play a role in the development
      of novel endomorphin analogues with increased therapeutic potential.

PMID- 22982725
TI  - Changes in brain structure during learning: fact or artifact? Reply to Thomas and
      Baker.
AB  - In their review in this issue, Thomas and Baker question the validity of
      longitudinal human neuroimaging studies that have claimed to demonstrate
      structural plasticity. This commentary identifies problems with some of the
      arguments raised in their review and suggests that there is strong evidence, from
      both animal and human studies, that experience can alter brain structure.

PMID- 22982726
TI  - Neuromagnetic index of hemispheric asymmetry predicting long-term outcome in
      sudden hearing loss.
AB  - The neuromagnetic index of hemispheric asymmetry in terms of
      ipsilateral/contralateral ratio at acute stage was previously revealed to
      prognosticate the 1-month hearing outcome of acute unilateral idiopathic sudden
      sensorineural hearing loss (ISSNHL), showing a dynamic relationship between top-
      and down-levels of auditory pathway. However, the prognostic effect of
      reorganization pattern for the long-term results remained elusive. This study
      aimed to probe the prognosticating relevance of hemispheric asymmetry to the
      hearing at chronic stage of ISSNHL. Using magnetoencephalography (MEG), inter
      hemispheric differences in peak dipole of N100m responses to monaural tones were
      evaluated in 21 controls and 21 ISSNHL patients at initial and final (12 months
      later) stages. Predictive value of hemispheric asymmetry was assessed by
      correlating hearing level and ipsilateral/contralateral ratio (I/C) of N100m
      latency and amplitude. Healthy-side dominance of N100m was observed in ISSNHL
      initially, and remained in three final prognostic subgroups (complete, partial,
      and no recovery) of ISSNHL. The initial I/C(amplitude) on affected-ear
      stimulation strongly correlated with the hearing level of final stage in ISSNHL.
      However, there was no prognostic effect of hemispheric asymmetry pattern for the
      12-month hearing improvement. The heterogeneity between neuromagnetic index and
      hearing levels possibly echoed different pathogeneses of ISSNHL. Since a restored
      hearing status did not necessarily lead toward a normal functional organization,
      the dynamics of hemispheric asymmetry could actually index a central resilient
      reorganization in the brain for sound processing in ISSNHL. Our finding showed
      not only a clinically relevant measure to predict final hearing of ISSNHL, but
      also a linkage between central plasticity and cochlear lesion. This finding
      suggests a new perspective, and perhaps new interventions, to diagnose and treat
      unilateral ISSNHL.

PMID- 22982727
TI  - Variations in the temporal pattern of perforant pathway stimulation control the
      activity in the mesolimbic pathway.
AB  - Signal processing in the hippocampal formation and resultant signal propagation
      to cortical and subcortical structures during high frequency stimulation (i.e.
      100 Hz) of the perforant pathway was studied in medetomidine anesthetized rats by
      functional magnetic resonance imaging (fMRI) and electrophysiological recordings.
      The perforant pathway was stimulated with bursts of 20 pulses, one burst per
      second, or with continuously applied pulses. The stimulation duration was
      adjusted to 8 s (short) or 30 s (long). In general, extending the stimulation
      duration only caused a local spreading of the fMRI response, but no changes in
      the magnitude of the fMRI response. This was in agreement with the
      electrophysiological responses, which also remained unchanged. In contrast,
      increasing the number of pulses in one stimulus train (i.e. changing from burst
      to continuous stimulation), caused both spreading and an increase in local fMRI
      responses that were accompanied by an altered neuronal response pattern.
      Continuous stimulation also triggered additional fMRI responses in the septum,
      nucleus accumbens, anterior cingulate cortex/medial prefrontal cortex, and
      ventral tegmental area/substantia nigra. The appearance of fMRI responses outside
      the hippocampal formation required at least 3 consecutive stimulation trains,
      characterized by region specific hemodynamic response functions. Thus, once
      triggered, continuous stimulation caused a sequential appearance in fMRI
      responses starting in the hippocampal formation, followed by signal changes in
      the ventral tegmental area/substantia nigra and anterior cingulate cortex/medial
      prefrontal cortex and eventually in the nucleus accumbens. These results indicate
      that high frequency stimulation of the hippocampal formation can activate the
      mesolimbic pathway, provided that repetitive stimulations are applied.

PMID- 22982728
TI  - HES6 enhances the motility of alveolar rhabdomyosarcoma cells.
AB  - HES6, a member of the hairy-enhancer-of-split family of transcription factors,
      plays multiple roles in myogenesis. It is a direct target of the myogenic
      transcription factor MyoD and has been shown to regulate the formation of the
      myotome in development, myoblast cell cycle exit and the organization of the
      actin cytoskeleton during terminal differentiation. Here we investigate the
      expression and function of HES6 in rhabdomyosarcoma, a soft tissue tumor which
      expresses myogenic genes but fails to differentiate into muscle. We show that
      HES6 is expressed at high levels in the subset of alveolar rhabdomyosarcomas
      expressing PAX/FOXO1 fusion genes (ARMSp). Knockdown of HES6 mRNA in the ARMSp
      cell line RH30 reduces proliferation and cell motility. This phenotype is rescued
      by expression of mouse Hes6 which is insensitive to HES6 siRNA. Furthermore,
      expression microarray analysis indicates that the HES6 knockdown is associated
      with a decrease in the levels of Transgelin, (TAGLN), a regulator of the actin
      cytoskeleton. Knockdown of TAGLN decreases cell motility, whilst TAGLN
      overexpression rescues the motility defect resulting from HES6 knockdown. These
      findings indicate HES6 contributes to the pathogenesis of ARMSp by enhancing both
      proliferation and cell motility.

PMID- 22982729
TI  - Molecular determinants for the line tension of coexisting liquid phases in
      monolayers.
AB  - The line tension (lambda) in biphasic membranes has been determined in monolayers
      and bilayers using a variety of techniques. In this work we present a novel
      approach to the determination of lambda in monolayers with liquid/liquid phase
      coexistence, overcoming several of the drawbacks of current techniques. Using our
      method, we determined the line tension of liquid/liquid phases in binary mixtures
      of different lipids and a molecule similar to cholesterol but less oxidizable. We
      analyzed the effect of the hydrocarbon chain length and the polar head-group of
      the non-sterol lipid and found the latter to exert much more influence than the
      former. The presence of PE led to high lambda values, PG to low values and PS and
      PC to intermediate values. The line tension showed a strong correlation with the
      critical packing parameter of the phospholipid. The spontaneous curvature
      displayed by the phases constituted by a particular lipid appears to be an
      important parameter for determining the line tension in mixed films.

PMID- 22982730
TI  - Alpha-lipoic acid pre- and post-treatments provide protection against in vitro
      ischemia-reperfusion injury in cerebral endothelial cells via Akt/mTOR signaling.
AB  - Alpha-lipoic acid (ALA) is an endogenous short-chain fatty acid that has
      beneficial protective effects against various vascular diseases. In this study,
      we sought to determine whether ALA could induce pre- or post-treatment protective
      effects against simulated ischemia and reperfusion-induced cerebral endothelial
      cell (CEC) injury by activating the Akt/mTOR pathway. CECs are currently
      considered to be an important target for ischemia therapy. Mouse brain
      endothelial cells (bEnd.3) and primary cultures of CECs were subjected to 6h of
      oxygen glucose deprivation (OGD) followed by 4h of simulated reperfusion, either
      alone or together with ALA administration before (pre-treatment) or immediately
      after (post-treatment) OGD. We found that pre-treatment administration of ALA
      reduced the OGD and simulated reperfusion-induced lactate dehydrogenase (LDH)
      release in bEnd.3 cells in a dose-dependent manner and that 1mM ALA pre- and post
      treatments provided protection in both bEnd.3 cells and primary cultures of CECs.
      However, rapamycin, an mTOR inhibitor, was able to thoroughly abolish the
      protective effects of ALA. Western blotting showed that the ALA pre- and post
      treatments up-regulated the phosphorylation of Akt, mTOR, S6K and 4E-BP1 in both
      bEnd.3 cells and primary cultures. However, after pre-treatment with rapamycin,
      the level of Akt phosphorylation was decreased in primary cultures of CECs but
      could still be restored by ALA, whereas the levels of mTOR, S6K and 4E-BP1
      phosphorylation were significantly decreased and could not be restored. These
      results suggest that ALA pre- and post-treatments provide protective effects
      against simulated ischemia and reperfusion-induced CEC injury by promoting the
      Akt/mTOR pathway and that mTOR is required for ALA protection.

PMID- 22982731
TI  - Neuroprotective cyclopentenone prostaglandins up-regulate neurotrophic factors in
      C6 glioma cells.
AB  - In a previous study, we developed newly synthesized arylthio derivatives of
      cyclopentenone prostaglandins (GIF-0642, GIF-0643, GIF-0644, GIF-0745 and GIF
      0747), which are neuroprotective against both manganese toxicity in PC12 cells
      and glutamate toxicity in HT22 cells. In the present study, we showed that these
      compounds and their lead compound, NEPP11, are potent inducers of glial cell line
      derived neurotrophic factor (GDNF) expression in C6 glioma cells and primary
      astrocytes. These neuroprotective cyclopentenone prostaglandins also induced the
      gene expression of nerve growth factor and, to a lesser extent, brain-derived
      neurotrophic factor. The induction of GDNF mRNA was transcription-dependent, and
      the overexpression of dominant-negative Nrf2 attenuated the ability of the
      (arylthio)cyclopentenone prostaglandins to stimulate GDNF gene expression. These
      results suggest that (arylthio)cyclopentenone prostaglandins increase GDNF gene
      expression partly via the Keap1/Nrf2 pathway. A growing number of reports
      demonstrate the importance of increasing the amounts of neurotrophic factors,
      especially GDNF, in neuropathological states. Although the precise mechanisms by
      which the GIF compounds inhibit cell death are under investigation, an increase
      in neurotrophic factors may contribute to the diverse pharmacological properties
      of (arylthio)cyclopentenone prostaglandins in vivo and will make them potentially
      valuable in the treatment of neurodegenerative disorders.

PMID- 22982732
TI  - The ability of animal studies to detect serious post marketing adverse events is
      limited.
AB  - The value of animal studies to assess drug safety is unclear because many such
      studies are biased and have methodological shortcomings. We studied whether post
      marketing serious adverse reactions to small molecule drugs could have been
      detected on the basis of animal study data included in drug registration files.
      Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were
      identified in animal studies as a true positive outcome, which suggests that data
      from animal studies are of limited value to pharmacovigilance activities. Our
      study shows that drug registration files can be used to study the predictive
      value of animal studies and that the value of animal studies in all stages of the
      drug development should be investigated in a collaborative endeavour between
      regulatory authorities, industry, and academia.

PMID- 22982733
TI  - A novel dry powder inhalable formulation incorporating three first-line anti
      tubercular antibiotics.
AB  - Treatment for tuberculosis (TB) using the standard oral antibiotic regimen is
      effective but inefficient, requiring high drug dosing and lengthy treatment
      times. Three concurrent first-line antibiotics recommended by the World Health
      Organization (WHO) guidelines are pyrazinamide, rifampicin and isoniazid.
      Combining these antibiotics in a novel formulation for dry powder inhalation
      (DPI) may facilitate rapid and efficient resolution of local and systemic
      infection. However, spray-dried individually, these antibiotics were found to be
      physically unstable. A solution of the three antibiotics, at the WHO-recommended
      ratio, was spray-dried. The collected powder was assessed by a series of in vitro
      methods to investigate aerosol performance, particle physico-chemical
      characteristics and dissolution profile. Particles obtained were spherical with a
      surface composed primarily of rifampicin, as identified by TOF-SIMS. A mass
      median aerodynamic diameter of 3.5 +/- 0.1 MUm and fine particle fraction (<5
      MUm) of 45 +/- 3% indicated excellent aerosol performance. The combination powder
      was differentiated by the presence of rifampicin dihydrate and the delta
      polymorph of pyrazinamide. Quantitative analysis indicated individual particles
      contained the three antibiotics at the expected proportions (400:150:75 w/w).
      This excipient-free triple antibiotic DPI formulation could be used as a
      significant enhanced treatment for TB.

PMID- 22982734
TI  - Through the lens of implementation science: next steps in understanding the
      significance of organizational justice.

PMID- 22982735
TI  - The quality of advanced dementia care in the nursing home: the role of special
      care units.
AB  - BACKGROUND: The quality of nursing home care for residents with advanced dementia
      has been described as suboptimal. One relatively understudied factor is the
      impact of special care units (SCUs) for dementia for residents at the end stage
      of this disease. OBJECTIVE: To examine the association between residence in an
      SCU and the quality of end-of-life care for nursing home residents with advanced
      dementia. RESEARCH DESIGN: This study used longitudinal data on 323 nursing home
      residents with advanced dementia living in 22 Boston-area facilities. Using
      multivariate methods, we analyzed the association between residence in an SCU and
      measures of quality of end-of-life care including: treatment of pain and dyspnea,
      prevalence of pressure ulcers, hospitalization, tube feeding, antipsychotic drug
      use, advance care planning, and health care proxy (HCP) satisfaction with care.
      RESULTS: A total of 43.7% residents were cared for in an SCU. After multivariate
      adjustment, residents in SCUs were more likely to receive treatment for dyspnea,
      had fewer hospitalizations, were less likely to be tube fed, and more likely to
      have a do-not-hospitalize order, compared with non-SCU residents. However, non
      SCU residents were more likely to be treated for pain, had fewer pressure ulcers,
      and less frequent use of antipsychotic drugs than SCU residents. HCPs of SCU
      residents reported greater satisfaction with care than HCPs of non-SCU residents.
      CONCLUSIONS: Residence in an SCU is associated with some, but not all, markers of
      better quality end-of-life care among nursing home residents with advanced
      dementia.

PMID- 22982737
TI  - Limitations of using billing databases in an attempt to compare cataract surgery
      outcomes in Veterans Health Administration versus Medicare.

PMID- 22982736
TI  - Geographical access and the substitution of traditional healing for biomedical
      services in 2 American Indian tribes.
AB  - OBJECTIVES: American Indians who live in rural reservation communities face
      substantial geographic barriers to care that may limit their use of health
      services and contribute to their well-documented health disparities. The purpose
      of this study was to examine the impact of geographical access to care on the use
      of services for physical and mental health problems and to explore American
      Indians' use of traditional healing services in relation to use of biomedical
      services. METHODS: We analyzed survey data collected from 2 tribes (Southwest and
      Northern Plains). Geographical access to the closest biomedical service was
      measured using a Geographic Information System, including road travel distance,
      elevation gain, and reservation boundary crossing. RESULTS: Use of biomedical
      services was unaffected by geographical access for Northern Plains tribal members
      with mental health problems and for Southwest tribal members with physical or
      mental health problems. For members of the Northern Plains tribe with physical
      health problems, travel distance (P=0.007) and elevation gain (P=0.029)
      significantly predicted a lower likelihood of service use. The use of traditional
      healing was unrelated to biomedical service use for members of the Northern
      Plains tribe with physical or mental health problems and for members of the
      Southwest tribe with physical health problems. For members of the Southwest tribe
      with mental health problems, the use of biomedical services increased the
      likelihood of using traditional healing services. CONCLUSIONS: Findings suggest
      that biomedical services are geographically accessible to most tribal members and
      that tribal members are not substituting traditional healing for biomedical
      treatments because of poor geographical access.

PMID- 22982739
TI  - 5-HT(1A) receptor binding in the dorsal raphe nucleus is implicated in the
      anxiolytic-like effects of Cinnamomum cassia.
AB  - Previously we reported that the 50% EtOH extract of Cinnamomum cassia (C. cassia)
      possesses anxiolytic-like activity in the mouse elevated plus maze (EPM) test.
      This activity was blocked by the 5-HT(1A) receptor antagonist, WAY 100635.
      Therefore, in order to investigate the effect of C. cassia on 5-HT(1A) receptor
      binding, quantitative autoradiography of 5-HT(1A) receptors was carried out in
      brains of mice treated acutely and repeatedly with C. cassia. Binding of [(3)H]8
      OH-DPAT to the 5-HT(1A) receptor was investigated in the mouse brain. After a
      single treatment of C. cassia (750 mg/kg, p.o.), [(3)H]8-OH-DPAT binding showed a
      significant increase in the dorsal raphe nucleus (DRN). After repeated treatment
      with C. cassia (100mg/kg, once a day for 5 days, p.o.), [(3)H]8-OH-DPAT binding
      showed no significant change in any brain region. Taken together, the anxiolytic
      like effect of the 50% EtOH extract of C. cassia might be mediated by region
      specific change of 5-HT(1A) receptors in the dorsal raphe nucleus.

PMID- 22982740
TI  - Effects of caffeic acid on behavioral parameters and on the activity of
      acetylcholinesterase in different tissues from adult rats.
AB  - Acetylcholinesterase (AChE) is distributed throughout the body in both neuronal
      and non-neuronal tissues and plays an important role in the regulation of
      physiological events. Caffeic acid is a phenolic compound that has anti
      inflammatory and neuroprotective properties. The aim of this study was to
      investigate in vitro and in vivo whether caffeic acid alters the AChE activity
      and behavioral parameters in rats. In the in vitro study, the concentrations of
      0, 0.1, 0.5, 1.0, 1.5, and 2mM of caffeic acid were used. For the in vivo study,
      five groups were evaluated: group I (control); group II (canola oil), group III
      (10mg/kg of caffeic acid); group IV (50mg/kg of caffeic acid) and group V
      (100mg/kg of caffeic acid). Caffeic acid was diluted in canola oil and
      administered for 30 days. In vitro, the caffeic acid increased the AChE activity
      in the cerebral cortex, cerebellum, hypothalamus, whole blood, and lymphocytes at
      different concentrations. In muscle, this compound caused an inhibition in the
      AChE activity at concentrations of 0.5, 1.0, 1.5, and 2mM when compared to the
      control (P<0.05). In vivo, 50 and 100mg/kg of caffeic acid decreased the AChE
      activity in the cerebral cortex and striatum and increased the activity of this
      enzyme in the cerebellum, hippocampus, hypothalamus, pons, lymphocytes, and
      muscles when compared to the control group (P<0.05). The amount of 100mg/kg of
      caffeic acid improved the step-down latencies in the inhibitory avoidance. Our
      results demonstrated that caffeic acid improved memory and interfered with the
      cholinergic signaling. As a natural and promising compound caffeic acid should be
      considered potentially therapeutic in disorders that involve the cholinergic
      system.

PMID- 22982741
TI  - Effect of dexmedetomidine on ejaculatory behavior and sexual motivation in intact
      male rats.
AB  - Premature ejaculation is the most common sexual disorder in young men.
      Consequently, there is an intense search for efficient and safe pharmacological
      treatments. Insofar, almost no effective treatment with acute effects is
      available. In this study, we evaluated the effects of the noradrenergic alpha(2)
      receptor agonist dexmedetomidine on sexual incentive motivation and copulatory
      behavior in male rats. Sexual incentive motivation was tested in a large
      rectangular arena connected to two small incentive stimulus cages containing
      either a male or sexually receptive female rat. There was no sexual interaction
      possible between the experimental subjects and the incentives during this test.
      Approach to the incentives constituted the measure of sexual incentive
      motivation. After the sexual incentive motivation test, the subjects were tested
      for copulatory behavior in a regular copulation test for 30min. Doses of 0.1 and
      1MUg/kg of dexmedetomidine (i.p.) had no effect on any of the indices of
      locomotor activity or on parameters of sexual incentive motivation. With regard
      to copulatory behavior, it was found that the dose of 1MUg/kg prolonged the
      latency to the first ejaculation, while the latency to second ejaculation showed
      a tendency to increase. The absence of an effect on indices of sexual incentive
      motivation or general activity showed that the actions of dexmedetomidine in this
      study were limited to ejaculatory mechanisms. Insofar as the ejaculation latency
      in the male rat is predictive of prolonged ejaculation latency in men, it can be
      proposed that dexmedetomidine is of potential utility for the treatment of
      premature ejaculation.

PMID- 22982742
TI  - Energy-converting respiratory Complex I: on the way to the molecular mechanism of
      the proton pump.
AB  - In respiring organisms the major energy transduction flux employs the
      transmembrane electrochemical proton gradient as a physical link between
      exergonic redox reactions and endergonic ADP phosphorylation. Establishing the
      gradient involves electrogenic, transmembrane H(+) translocation by the membrane
      embedded respiratory complexes. Among others, Complex I (NADH:ubiquinone
      oxidoreductase) is the most structurally complex and functionally enigmatic
      respiratory enzyme; its molecular mechanism is as yet unknown. Here we highlight
      recent progress and discuss the catalytic events during Complex I turnover in
      relation to their role in energy conversion and to the enzyme structure.

PMID- 22982743
TI  - A re-assigned American mink (Neovison vison) map optimal for genome-wide studies.
AB  - Our previously published second generation genetic map for the American mink
      (Neovison vison) has been used and redesigned in its best for genome-wide studies
      with maximum of efficiency. A number of 114 selected markers, including 33 newly
      developed microsatellite markers from the CHORI-231 mink Bacterial Artificial
      Chromosome (BAC) library, have been genotyped in a two generation population
      composed of 1200 individuals. The outcome reassigns the position of some markers
      on the chromosomes and it produces a more reliable map with a convenient distance
      between markers. A total of 104 markers mapped to 14 linkage groups corresponding
      to the mink autosomes. Six markers are unlinked and four markers are allocated to
      the X chromosome by homology but no linkage was detected. The sex-average linkage
      map spans 1192 centiMorgans (cM) with an average intermarker distance of 11.4cM
      and 1648cM when the ends of the linkage groups and the autosomal unlinked markers
      are added. Sex-specific genetic linkage maps were also generated. The male sex
      specific map had a total length of 1014.6cM between the linked markers and an
      average inter-marker interval of 9.7cM. The female map has a corresponding length
      of 1378.6cM and an average inter-marker interval of 13.3cM. The study is
      complemented with additional anchorage for most of the chromosomes of the map by
      BAC in situ hybridization with clones containing microsatellites strategically
      selected from the various parts of the genome. This map provides an improved tool
      for genetic mapping and comparative genomics in mink, also useful for the future
      assembly of the mink genome sequence when this will be taken forward.

PMID- 22982744
TI  - A peculiar mutation in the DNA-binding/dimerization domain of NFIX causes Sotos
      like overgrowth syndrome: a new case.
AB  - The Nuclear Factor I-X (NFIX) is a member of the nuclear factor I (NFI) family
      proteins, which are implicated as site-specific DNA-binding proteins and is
      deleted or mutated in a subset of patients with Sotos-like overgrowth syndrome
      and in patients with Marshall-Smith syndrome. We evaluated an additional patient
      with clinical features of Sotos-like syndrome by sequencing analysis of the NFIX
      gene and identified a 21 nucleotide in frame deletion predicting loss of 7 amino
      acids in the DNA-binding/dimerization domain of the NFIX protein. The deleted
      residues are all evolutionally conserved amino acids. The present report further
      confirms that mutations in DNA-binding/dimerization domain cause
      haploinsufficiency of the NFIX protein and strongly suggests that in individuals
      with Sotos-like features unrelated to NSD1 changes genetic testing of NFIX should
      be considered.

PMID- 22982745
TI  - The updated beers criteria: promoting use of evidence-based medications in the
      elderly.
AB  - For more than two decades, the Beers criteria, which lists potentially
      inappropriate medications for use in older adults, has been a cornerstone to
      providing optimal pharmaceutical care to elderly patients. Updates to the Beers
      criteria were added in 2012. All practitioners caring for elderly patients should
      have a thorough understanding of the criteria, which are increasingly referenced
      and used by clinicians and policymakers alike.

PMID- 22982746
TI  - Diverticular disease: eat your fiber!
AB  - In industrialized nations, diverticular disease affects up to 70% of individuals
      by 60 years of age, with symptoms that can range from mild gastrointestinal
      disturbance to incapacitating pain. Diverticular disease appears to be related to
      increasing affluence and changed diet: Current theory holds that diverticular
      disease's origin is low-fiber diet. This explains why its incidence is highest
      and accelerating in the more prosperous countries where intake of fiber has
      decreased and intake of milled grains and refined sugars has increased over time.
      Not all patients develop symptoms, but if they do, the most frequent complaints
      associated with diverticulosis are cramping in the left-lower quadrant, bloating,
      constipation, and soiling. If diverticula perforate the gut's wall into the
      pericolic tissue, small and large abscesses, accompanied by bleeding, can form.
      Fistulization, when it occurs, most often penetrates to the bladder. Treatment
      addresses symptoms and may require hospitalization. During symptomatic periods,
      patients do best on low-fiber, bland diets. Once the acute episode or highly
      symptomatic period resolves or chronic disease is managed, patients should
      gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in
      the form of bulk stimulants like psyllium.

PMID- 22982747
TI  - The prevalence and recognition of chronic kidney disease and anemia in long-term
      care residents.
AB  - OBJECTIVE: To evaluate the prevalence of chronic kidney disease (CKD) and anemia
      in the long-term care facility, the rate of recognition of these conditions, and
      the specific interventions used to treat anemia. DESIGN: Retrospective cross
      sectional analysis. SETTING: Twenty-seven long-term care facilities in Colorado.
      PATIENTS, PARTICIPANTS: Had > 90-day residency in the long-term care facility;
      had index serum creatinine and hemoglobin (Hb) values +/- 90 days of the earliest
      (index) Minimum Data Set (MDS). Data were derived from the AnalytiCare(sm)
      database (January 1, 2007-September 15, 2008) containing laboratory results, MDS
      reports, and pharmacy fills. Residents with laboratory-defined CKD had estimated
      glomerular filtration rates < 60 mL/min/1.73 m(2). Those with laboratory-defined
      anemia had < 12 g/dL Hb females, < 13 g/dL Hb males. MDS reports indicated
      recognition of CKD and anemia. Prescription records identified anemia-related
      pharmacotherapy for anemic residents. MAIN OUTCOME MEASUREMENTS: Prevalence rates
      of laboratory-defined CKD and anemia, recognition rates of anemia and CKD, and
      rates of use of specific anemia pharmacotherapies. RESULTS: For 838 eligible
      residents, laboratory findings showed a prevalence rate of 43% for CKD and 46%
      for anemia. Only 2.8% and 14.6% of residents with laboratory defined CKD had CKD
      recognized on the index, or any index or postindex MDS, respectively. Anemia
      recognition rates were 9.6% and 39.9%, respectively. No single anemia
      prescription therapy class (erythropoiesis stimulating agents, iron, vitamin
      B(12), or folic acid) was used for more than 10% of all residents with laboratory
      or MDS-defined anemia. CONCLUSION: For CKD and anemia, the lack of concordance
      between laboratory- and MDS-identified disease should alert health care
      professionals of potential under-recognition within the long-term care facility.

PMID- 22982748
TI  - Understanding insurance coverage in the senior market: reimbursement and emerging
      trends.
AB  - Currently, Medicare Part D is the primary payer of pharmaceuticals and driver of
      formulary selection for most seniors, regardless of their care setting. This
      primer examines key issues in reimbursement for geriatric care from a historical
      perspective and how it has affected health care professionals in their clinical
      and distributive functions. Discussion on how reimbursement trends evolved for
      older adult patients across care settings such as nursing facilities, assisted
      living, hospice, and home health are included. Additionally, this primer
      identifies what is changing across the different care settings, the complexities
      of medication coverage today, and current trends that may have significant impact
      on medication cost in the near future if the Affordable Care Act is implemented
      as currently written. Finally, the primer identifies legislative and regulatory
      initiatives and reimbursement trends that will continue to pose a challenge in
      the coming years as Congress and the president address the number of individuals
      covered by publicly funded programs. This challenge will be amplified in part by
      a growing biotechnology pharmaceutical pipeline and a rapidly increasing genomics
      industry.

PMID- 22982749
TI  - Differentiating the treatment of asthma and chronic obstructive pulmonary disease
      in the elderly patient.
AB  - The focus of this case is a 70-year-old female who was admitted to an assisted
      living community following a hospitalization for a severe asthma exacerbation.
      The diagnosis of asthma in the geriatric patient is often under-recognized,
      misdiagnosed, and improperly managed. Several factors may explain the
      misclassification and the undertreatment of asthma in the older patient. This
      case discusses the pharmacotherapeutic management of asthma in the geriatric
      patient and differentiates the clinical features of asthma from that of chronic
      obstructive lung disease. The comprehensive management of asthma should include
      an interprofessional approach because the consultant pharmacist is an essential
      member of the health care team.

PMID- 22982750
TI  - Senior centers: traditional and evolving roles.
AB  - The first senior center in the United States, the William Hodson Community Center
      in New York City, opened its doors in 1943. Its purpose was to reach out to
      people who had retired but needed a place to gather to stay connected to others.
      Senior centers serve as an entry point for the aging service network and protect
      against social isolation. One popular perception-that senior centers are welfare
      programs-has inhibited many elders from seeking services, and it needs to be
      dispelled. These centers do not just offer low-cost meals, nor provide
      institution-like services; they are diverse and vital institutions. Recent
      studies indicate that participation in senior centers has been declining, and
      center personnel are looking for new ways to reach the "young-old" who have yet
      to participate and the "old-old" who may face challenges getting to the center.
      Pharmacists are in the ideal position to offer health and wellness programming
      and caregiver education in this setting. Senior centers are also good places to
      train students, who are often surprised at the range of seniors' interests and
      cognitive abilities.

PMID- 22982751
TI  - A novel 2D binary collimator for IMRT dose delivery: dosimetric characterization
      using Monte Carlo simulations.
AB  - We present a novel technical concept of a two-dimensional binary multileaf
      collimator (2D-bMLC) especially designed for fast dose delivery in rotational
      IMRT. The 2D-bMLC consists of individually controlled absorber channels, which
      are arranged side by side forming a 2D collimator aperture. In each channel three
      separate tungsten modules are arranged behind each other. To open and close an
      element, the central module is shifted between two positions. The purpose of this
      work is the presentation of the 2D-bMLC concept and its dosimetric evaluation. To
      determine the dosimetric properties, we designed a Monte Carlo model of an
      exemplary 2D-bMLC, consisting of 30 * 30 elements. A virtual source model of a
      flattening filter-free 7 MV linac was used to characterize the linac phase space.
      A primary radiation efficiency factor of 43% was calculated for the open 2D-bMLC
      by dividing the integral dose scored for a 2D-bMLC field by the integral dose
      scored for an open field with the same dimensions. The leakage calculated for the
      closed collimator was below 0.5%. Following the primary photon fluence
      distribution, the bixel intensity decreases with the distance of the element to
      the central axis of the treatment machine. From the collimator field's center
      toward its borders, the geometric bixel widths increase in a symmetric and
      predictable manner by up to 4%. The increase is explained by the specific design
      of the 2D-bMLC. Abutting element beams exhibit a slight tongue-and-groove effect
      if opened sequentially. This effect as well as the primary radiation efficiency
      is basically affected by the source size and the dimensions of the collimator
      elements. We successfully established and evaluated a dosimetric model of the 2D
      bMLC. The results are promising, and we will therefore investigate on real
      patient plans, if the concept could be advantageous for fast rotational IMRT
      treatments.

PMID- 22982752
TI  - Tailored real-time scaling of heteronuclear couplings.
AB  - Heteronuclear couplings are a valuable source of molecular information, which is
      measured from the multiplet splittings of an NMR spectrum. Radiofrequency
      irradiation on one coupled nuclear spin allows to modify the effective coupling
      constant, scaling down the multiplet splittings in the spectrum observed at the
      resonance frequency of the other nuclear spin. Such decoupling sequences are
      often used to collapse a multiplet into a singlet and can therefore simplify NMR
      spectra significantly. Continuous-wave (cw) decoupling has an intrinsic non
      linear offset dependence of the scaling of the effective J-coupling constant.
      Using optimal control pulse optimization, we show that virtually arbitrary off
      resonance scaling of the J-coupling constant can be achieved. The new class of
      tailored decoupling pulses is named SHOT (Scaling of Heteronuclear couplings by
      Optimal Tracking). Complementing cw irradiation, SHOT pulses offer an alternative
      approach of encoding chemical shift information indirectly through off-resonance
      decoupling, which however makes it possible for the first time to achieve linear
      J scaling as a function of offset frequency. For a simple mixture of eight
      aromatic compounds, it is demonstrated experimentally that a 1D-SHOT {(1)H}-(13)C
      experiment yields comparable information to a 2D-HSQC and can give full
      assignment of all coupled spins.

PMID- 22982753
TI  - Prostaglandin E2 inhibits IL-23 and IL-12 production by human monocytes through
      down-regulation of their common p40 subunit.
AB  - The heterodimeric cytokine IL-23 is important for the maintenance of Th17 cells,
      which are pivotal mediators of autoimmune diseases like rheumatoid arthritis,
      colitis, and multiple sclerosis. Prostaglandin E2 (PGE2) is a soluble regulator
      of inflammation that has both pro- and anti-inflammatory properties. PGE2 has
      been shown to elevate the IL-23 production by dendritic cells (DC). Monocytes are
      also producers of IL-23 but the effect of PGE2 on IL-23 production by human
      monocytes has hardly been investigated. We show here that PGE2 blocks the
      production of IL-23 by LPS-stimulated monocytes in an IL-10 and IL-1beta
      independent manner. This effect was due to the down-regulation of the p40 subunit
      of IL-23 on mRNA and protein level. The p40 subunit is shared by IL-12 and,
      consistently, PGE2 also lowered the IL-12 production by monocytes. These effects
      of PGE2 were cAMP-dependent since the cAMP enhancer forskolin strongly reduced IL
      23 and IL-12 production by monocytes. Taken together, PGE2 acts in an anti
      inflammatory manner by lowering IL-23 production by monocytes while it has the
      opposite effect in DC. Our data may help to reconcile controversial point of
      views on the pro- and anti-inflammatory nature of PGE2 by making a strong case
      for a cell type-dependent function.

PMID- 22982755
TI  - Expression, purification and characterization of a human single-chain Fv antibody
      fragment fused with the Fc of an IgG1 targeting a rabies antigen in Pichia
      pastoris.
AB  - Because the demand for rabies post exposure prophylaxis (PEP) treatment has
      increased exponentially in recent years, the limited supply of human and equine
      rabies immunoglobulin (HRIG and ERIG) has failed to provide an adequate amount of
      the required passive immune component in PEP in countries where canine rabies is
      endemic. The replacement of HRIG and ERIG with a potentially cheaper and
      efficacious alternative biological for the treatment of rabies in humans,
      therefore, remains a high priority. In this study, we set out to assess a human
      single-chain Fv antibody fragment fused with the Fc of an IgG1 targeting a rabies
      antigen to develop a product that can be used as a component of the PEP cocktail.
      We cloned the ScFv fragment from a human ScFv library that was established
      previously and inserted this fragment into the expression vector pPICZalphaC/Fc.
      An active recombinant ScFv-Fc fusion protein was successfully expressed in Pichia
      pastoris. The production of ScFv-Fc was optimized and scaled up in an 80L
      fermentor with yields exceeding 60mg/L. The ScFv-Fc protein was purified to more
      than 95% purity using a two-step scheme: ammonium sulfate fractionation and
      Protein A Sepharose CL-4B. The ScFv-Fc fusion protein neutralized rabies virus in
      a standard in vivo neutralization assay in which the virus was incubated with the
      ScFv-Fc molecules before intracranial inoculation in mice. Our results suggest
      that functional antibodies can be produced in P. pastoris and that ScFv-Fc fusion
      proteins have the potential to serve as therapeutic candidates.

PMID- 22982754
TI  - Subtle changes in TCRalpha CDR1 profoundly increase the sensitivity of CD4 T
      cells.
AB  - Changes in the peptide and MHC molecules have been extensively examined for how
      they alter T cell activation, but many fewer studies have examined the TCR.
      Structural studies of how TCR differences alter T cell specificity have focused
      on broad variation in the CDR3 loops. However, changes in the CDR1 and 2 loops
      can also alter TCR recognition of pMHC. In this study we focus on two mutations
      in the CDR1alpha loop of the TCR that increased the affinity of a TCR for agonist
      Hb(64-76)/I-E(k) by increasing the on-rate of the reaction. These same mutations
      also conferred broader recognition of altered peptide ligands. TCR transgenic
      mice expressing the CDR1alpha mutations had altered thymic selection, as most of
      the T cells were negatively selected compared to T cells expressing the wildtype
      TCR. The few T cells that escaped negative selection and were found in the
      periphery were rendered anergic, thereby avoiding autoimmunity. T cells with the
      CDR1alpha mutations were completely deleted in the presence of Hb(64-76) as an
      endogenous peptide. Interestingly, the wildtype T cells were not eliminated,
      identifying a threshold affinity for negative selection where a 3-fold increase
      in affinity is the difference between incomplete and complete deletion. Overall,
      these studies highlight how small changes in the TCR can increase the affinity of
      TCR:pMHC but with the consequences of skewing selection and producing an
      unresponsive T cell.

PMID- 22982756
TI  - Lamotrigine monotherapy does not provide protection against the loss of optic
      nerve axons in a rat model of ocular hypertension.
AB  - Sodium channel blocking agents such as lamotrigine are potent agents for
      neuroprotection in several animal models of neurodegenerative and
      neuroinflammatory disease. We therefore explored whether lamotrigine therapy was
      neuroprotective in a rat model of ocular hypertension characterized by axonal
      injury and selective loss of retinal ganglion cells. Twenty-seven male Wistar
      rats were injected subcutaneously twice daily with either lamotrigine (14
      mg/kg/day) or vehicle. Two weeks after the first injection, experimental ocular
      hypertension was induced in one eye by 532 nm trabecular laser treatment.
      Intraocular pressure (IOP) was monitored by rebound tonometry and four weeks
      after the elevation of IOP the loss of optic nerve axons was quantified relative
      to eyes without either IOP elevation or lamotrigine exposure. In other animals
      with ocular hypertension, the optic nerves were examined by immunohistochemistry
      for the expression of the inducible form of nitric oxide synthase (iNOS) at 7 and
      28 days. Four weeks after initiation of IOP elevation, no significant difference
      in axonal loss was observed between rats treated with lamotrigine (30.8% +/-
      10.5%) or vehicle (17.8% +/- 5.7%) (P = 0.19, T-test). There was no significant
      difference in mean IOP, peak IOP and integral IOP exposure. Furthermore, optic
      nerve axon counts per unit integral IOP exposure were similar in both groups (P =
      0.44). The optic nerves were not positive for the expression of iNOS. In
      conclusion, this study provides no evidence that lamotrigine is neuroprotective
      for RGC axons after four weeks of experimental ocular hypertension in the rat, in
      a model where axonal degeneration occurs in the absence of iNOS expression.

PMID- 22982757
TI  - Human cytochrome P450-dependent differential metabolism among three 2alpha
      substituted-1alpha,25-dihydroxyvitamin D(3) analogs.
AB  - Our previous studies revealed that C2alpha-substituted-1alpha,25(OH)(2)D(3)
      analogs had unique biological activities. For example, 19-nor-2alpha-(3
      hydroxypropyl)-1alpha,25(OH)(2)D(3) (MART-10), which has a high affinity for
      vitamin D receptor (VDR), is more bioavailable and more potent than
      1alpha,25(OH)(2)D(3) in inhibiting cancer cell growth and invasion because of its
      weaker binding to vitamin D binding protein (DBP), and more resistance to CYP24A1
      dependent metabolism. In this study, we examined the metabolism of MART-10 and
      two other 2alpha-substituted analogs, 2alpha-(3-hydroxypropoxy)
      1alpha,25(OH)(2)D(3) (O2C3) and 2alpha-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3)
      (O1C3) by using human liver microsomes and human P450s. We demonstrated that O2C3
      was converted to 1alpha,2alpha,25(OH)(3)D(3) in human liver microsomes, whereas
      both O1C3 and MART-10 were hardly metabolized. The metabolism of O2C3 was
      significantly inhibited by ketoconazole, and the recombinant human CYP3A4
      converted O2C3 to 1alpha,2alpha,25(OH)(3)D(3), which suggests that CYP3A4 is
      responsible for the metabolism of O2C3 in human liver. The k(cat)/K(m) values of
      CYP3A4 for O1C3 and MART-10 are much smaller than that for O2C3. The k(cat)/K(m)
      values of human CYP24A1 for the three analogs are 1% (MART-10), 3% (O2C3), and 4%
      (O1C3) of that for 1alpha,25(OH)(2)D(3), indicating that MART-10 is the most
      resistant to CYP24A1 hydroxylation. On the other hand,
      1alpha,2alpha,25(OH)(3)D(3), the metabolite of O2C3 by CYP3A4, was metabolized by
      CYP24A1 via multiple pathways similar to 1alpha,25(OH)(2)D(3), which suggests
      that O2C3 can be metabolized by two sequential hydroxylations, first by CYP3A4
      and then by CYP24A1 in human body. These results suggest that modification at C
      2alpha position and C-19 demethylenation markedly change metabolic profiles and
      biological activities of vitamin D analogs.

PMID- 22982758
TI  - Deep evolutionary lineages in a Western Mediterranean snake (Vipera
      latastei/monticola group) and high genetic structuring in Southern Iberian
      populations.
AB  - Phylogeographic studies during the last decade confirmed an internal complexity
      of the Iberian Peninsula and northern Maghreb as refugial areas during the
      Miocene to Pleistocene period. Species with low vagility that experienced the
      complex climatic and palaeogeographic processes occurred in the Western
      Mediterranean Basin are excellent candidates to study the extent of lineage
      diversification in this region. We applied phylogenetic analyses based on
      mitochondrial data to infer the evolutionary history of Vipera latastei/monticola
      and identify the major biogeographic events structuring the genetic diversity
      within this group. We obtained a well-resolved phylogeny, with four highly
      divergent lineages (one African and three Iberian) that originated in the
      Tertiary. Coalescence-based estimations suggest that the differentiation of the
      four major lineages in V. latastei/monticola corresponds to the Messinian
      salinity crisis and the reopening of the Strait of Gibraltar during the Miocene.
      Subsequent Pliocene and Pleistocene climatic oscillations continued to isolate
      both Iberian and Maghrebian populations and led to a high genetic structuring in
      this group, particularly in Southern Iberia, a complex palaeogeographic and
      topographic region with high endemism levels. This study does not support the
      current taxonomy of the group, thus suggesting that an integrative evaluation of
      Iberian and African populations is needed to resolve its systematics.

PMID- 22982759
TI  - Life history and biogeographic diversification of an endemic western North
      American freshwater fish clade using a comparative species tree approach.
AB  - The west coast of North America contains a number of biogeographic freshwater
      provinces which reflect an ever-changing aquatic landscape. Clues to
      understanding this complex structure are often encapsulated genetically in the
      ichthyofauna, though frequently as unresolved evolutionary relationships and
      putative cryptic species. Advances in molecular phylogenetics through species
      tree analyses now allow for improved exploration of these relationships. Using a
      comprehensive approach, we analyzed two mitochondrial and nine nuclear loci for a
      group of endemic freshwater fish (sculpin-Cottus) known for a wide ranging
      distribution and complex species structure in this region. Species delimitation
      techniques identified three novel cryptic lineages, all well supported by
      phylogenetic analyses. Comparative phylogenetic analyses consistently found five
      distinct clades reflecting a number of unique biogeographic provinces. Some
      internal node relationships varied by species tree reconstruction method, and
      were associated with either Bayesian or maximum likelihood statistical approaches
      or between mitochondrial, nuclear, and combined datasets. Limited cases of
      mitochondrial capture were also evident, suggestive of putative ancestral
      hybridization between species. Biogeographic diversification was associated with
      four major regions and revealed historical faunal exchanges across regions.
      Mapping of an important life-history character (amphidromy) revealed two separate
      instances of trait evolution, a transition that has occurred repeatedly in
      Cottus. This study demonstrates the power of current phylogenetic methods, the
      need for a comprehensive phylogenetic approach, and the potential for sculpin to
      serve as an indicator of biogeographic history for native ichthyofauna in the
      region.

PMID- 22982760
TI  - Estimating divergence dates and evaluating dating methods using phylogenomic and
      mitochondrial data in squamate reptiles.
AB  - Recently, phylogenetics has expanded to routinely include estimation of clade
      ages in addition to their relationships. Various dating methods have been used,
      but their relative performance remains understudied. Here, we generate and
      assemble an extensive phylogenomic data set for squamate reptiles (lizards and
      snakes) and evaluate two widely used dating methods, penalized likelihood in r8s
      (r8s-PL) and Bayesian estimation with uncorrelated relaxed rates among lineages
      (BEAST). We obtained sequence data from 25 nuclear loci (~500-1,000 bp per gene;
      19,020bp total) for 64 squamate species and nine outgroup taxa, estimated the
      phylogeny, and estimated divergence dates using 14 fossil calibrations. We then
      evaluated how well each method approximated these dates using random subsets of
      the nuclear loci (2, 5, 10, 15, and 20; replicated 10 times each), and using ~1
      kb of the mitochondrial ND2 gene. We find that estimates from r8s-PL based on 2,
      5, or 10 loci can differ considerably from those based on 25 loci (mean absolute
      value of differences between 2-locus and 25-locus estimates were 9.0 Myr).
      Estimates from BEAST are somewhat more consistent given limited sampling of loci
      (mean absolute value of differences between 2 and 25-locus estimates were 5.0
      Myr). Most strikingly, age estimates using r8s-PL for ND2 were ~68-82 Myr older
      (mean=73.1) than those using 25 nuclear loci with r8s-PL. These results show that
      dates from r8s-PL with a limited number of loci (and especially mitochondrial
      data) can differ considerably from estimates derived from a large number of
      nuclear loci, whereas estimates from BEAST derived from fewer nuclear loci or
      mitochondrial data alone can be surprisingly similar to those from many nuclear
      loci. However, estimates from BEAST using relatively few loci and mitochondrial
      data could still show substantial deviations from the full data set (>50 Myr),
      suggesting the benefits of sampling many nuclear loci. Finally, we found that
      confidence intervals on ages from BEAST were not significantly different when
      sampling 2 vs. 25 loci, suggesting that adding loci decreased errors but did not
      increase confidence in those estimates.

PMID- 22982761
TI  - Preparing promotoras to deliver health programs for Hispanic communities:
      training processes and curricula.
AB  - Training is an essential component of health programs that incorporate promotoras
      de salud (the Spanish term for community health workers) in the delivery of
      health education and behavioral interventions to Hispanics. During training
      sessions, promotoras are exposed to information and skill-building activities
      they need to implement the health programs. This analysis was one component of a
      broader study which explored program planners' approaches to recruiting and
      training promotoras to deliver and sustain health promotion programs for Hispanic
      women. The purpose of this study was to examine promotora-curriculum and training
      processes used to prepare promotoras to deliver health programs. The authors
      examined transcripts of 12 in-depth interviews with program planners and
      conducted a content analysis of seven different training materials used in their
      respective promotora programs. Interview themes and narratives included program
      planners' varying conceptualizations of promotora-training, including their
      personal definitions of "training the trainer," the practice of training a cadre
      of promotoras before selecting those best fit for the program, and the importance
      of providing goal-directed, in-depth training and supervision for promotoras. The
      content analysis revealed a variety of strategies used to make the training
      materials interactive and culturally competent. Study implications describe the
      importance of planners' provision of ongoing, goal-directed, and supervised
      training using both appropriate language and interactive methods to engage and
      teach promotoras.

PMID- 22982763
TI  - Gender differences in the liver micronucleus test in rats with partial
      hepatectomy.
AB  - The liver micronucleus test in rats with partial hepatectomy is a useful method
      to detect pro-clastogens such as diethylnitrosamine, the active metabolites of
      which do not reach the bone marrow due to their short lifespan. We have already
      reported that structural or numerical chromosome aberration inducers should be
      given before or after partial hepatectomy, respectively, to detect genotoxicity
      in the liver of rats. In the present study, we found that the percentage of
      binucleated cells in the liver from naive male rats is approximately 60% of that
      in female rats, which suggests a gender difference in the response to chromosome
      aberration inducers. Therefore, we investigated the responses to structural
      chromosome aberration inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and
      numerical chromosome aberration inducers (colchicine and carbendazim) in male and
      female rats. The chemicals were given to 8-week-old male and female F344 rats a
      day before or after partial hepatectomy and hepatocytes were isolated 4 days
      after the partial hepatectomy. As the results, diethylnitrosamine and 1,2
      dimethylhydrazine produced a significant increase in the frequency of
      micronucleated hepatocytes in both genders and the responses were comparable. In
      the case of colchicine and carbendazim, higher frequencies in the micronucleated
      hepatocytes were obtained in males than in females. Taken together, the response
      to chromosome aberration inducers in male rats was equal to or stronger than that
      in female rats. It seems that the use of only male rats in the liver micronucleus
      test is sufficient, unless existing data indicate a toxicologically meaningful
      gender difference in rats.

PMID- 22982762
TI  - The R-spondin family of proteins: emerging regulators of WNT signaling.
AB  - Recently, the R-spondin (RSPO) family of proteins has emerged as important
      regulators of WNT signaling. Considering the wide spectrum of WNT signaling
      functions in normal biological processes and disease conditions, there has been a
      significantly growing interest in understanding the functional roles of RSPOs in
      multiple biological processes and determining the molecular mechanisms by which
      RSPOs regulate the WNT signaling pathway. Recent advances in the RSPO research
      field revealed some of the in vivo functions of RSPOs and provided new
      information regarding the mechanistic roles of RSPO activity in regulation of WNT
      signaling. Herein, we review recent progress in RSPO research with an emphasis on
      signaling mechanisms and biological functions.

PMID- 22982764
TI  - An in vitro investigation of endocrine disrupting effects of trichothecenes
      deoxynivalenol (DON), T-2 and HT-2 toxins.
AB  - Trichothecenes are a large family of chemically related mycotoxins.
      Deoxynivalenol (DON), T-2 and HT-2 toxins belong to this family and are produced
      by various species of Fusarium. The H295R steroidogenesis assay, regulation of
      steroidogenic gene expression and reporter gene assays (RGAs) for the detection
      of androgen, estrogen, progestagen and glucocorticoid (ant)agonist responses,
      have been used to assess the endocrine disrupting activity of DON, T-2 and HT-2
      toxins. H295R cells were used as a model for steroidogenesis and gene expression
      studies and exposed with either DON (0.1-1000ng/ml), T-2 toxin (0.0005-5ng/ml) or
      HT-2 toxin (0.005-50ng/ml) for 48h. We observed a reduction in hormone levels in
      media of exposed cells following radioimmunoassay. Cell viability was determined
      by four colorimetric assays and we observed reduced cell viability with
      increasing toxin concentrations partly explaining the significant reduction in
      hormone levels at the highest toxin concentration of all three trichothecenes.
      Thirteen of the 16 steroidogenic genes analyzed by quantitative real time PCR (RT
      qPCR) were significantly regulated (P<0.05) by DON (100ng/ml), T-2 toxin
      (0.5ng/ml) and HT-2 toxin (5ng/ml) compared to the control, with reference genes
      (B2M, ATP5B and ACTB). Whereas HMGR and CYP19 were down-regulated, CYP1A1 and
      CYP21 were up-regulated by all three trichothecenes. DON further up-regulated
      CYP17, HSD3B2, CYP11B2 and CYP11B1 and down-regulated NR5A1. T-2 toxin caused
      down-regulation of NR0B1 and NR5A1 whereas HT-2 toxin induced up-regulation of
      EPHX and HSD17B1 and down-regulation of CYP11A and CYP17. The expressions of
      MC2R, StAR and HSD17B4 genes were not significantly affected by any of the
      trichothecenes in the present study. Although the results indicate that there is
      no evidence to suggest that DON, T-2 and HT-2 toxins directly interact with the
      steroid hormone receptors to cause endocrine disruption, the present findings
      indicate that exposure to DON, T-2 toxin and HT-2 toxin have effects on cell
      viability, steroidogenesis and alteration in gene expression indicating their
      potential as endocrine disruptors.

PMID- 22982766
TI  - It's time to stop using 20/20 in the clinic.

PMID- 22982767
TI  - Measuring the modulus of silicone hydrogel contact lenses.
AB  - PURPOSE: The purpose of this study is to demonstrate a novel method for measuring
      the modulus of contact lenses in their as-received, variable-thickness form and
      to determine whether modulus varies with location within commercial lenses and
      whether it is dependent on lens geometry and temperature. METHODS: The thickness
      profiles of lenses having powers from -8 diopters (D) to +4 D were measured using
      a Rehder electronic thickness gauge. Strip-shaped specimens having a width of 5.5
      mm were then cut from the lenses. Graphite particles were sprinkled on the
      specimen surface so that its motions could be tracked using digital image
      correlation techniques. The specimens were mounted in a BioTester test system
      using BioRakes (rather than clamps) and stretched uniaxially until all parts of
      the lens between the attachment points had elongated by at least 10%. This
      procedure allowed local modulus values to be determined at 110 locations over the
      surface of each lens and any property variations within the lenses to be
      characterized. Tests were performed at 5, 23, and 37 degrees C. RESULTS: Material
      modulus was found to be essentially constant within any given lens and was
      independent of the optical power of the lens. Young's Modulus values ranged from
      0.3 to 1.9 MPa, depending on the lens manufacturer and product, and some lens
      materials showed a decrease in modulus with temperature. For the materials
      tested, those with lower water content had a tendency to exhibit higher moduli.
      CONCLUSIONS: Testing of the kind reported here is important for assessing the
      efficacy of current and proposed contact lens materials and designs, especially
      if such designs make use of variable properties to enhance function or fit.

PMID- 22982765
TI  - Estrogenic effects of fusarielins in human breast cancer cell lines.
AB  - The fusarielins are a group of metabolites found in several Aspergillus and
      Fusarium species that have been reported to have with weak antifungal, antibiotic
      and cytotoxic effects. This study identifies fusarielin A, F, G and H isolated
      from Fusarium as mycoestrogens. Mycoestrogens are compounds from fungi that bind
      to the estrogen receptors and induce an estrogenic response in targeted cells.
      All four tested fusarielins stimulate MCF-7 cell proliferation with fusarielin H
      as the most potent, able to stimulate cell proliferation 4-fold in a resazurin
      metabolism assay at 25MUM. MDA-MB-231 cells without the estrogen receptor-alpha
      and MCF-10a cells without estrogen receptors were not stimulated by fusarielins.
      Furthermore, the stimulation was prevented in MCF-7 cells when fusarielins were
      incubated in the presence of the estrogen receptor antagonist fulvestrant. These
      observations suggest that fusarielins bind to the estrogen receptor and act as
      weak mycoestrogens.

PMID- 22982768
TI  - Exploring pre-school vision screening in primary care offices in Alabama.
AB  - PURPOSE: To investigate practices, barriers, and facilitators of universal pre
      school vision screening (PVS) at pediatric primary care offices. METHODS: Focus
      group sessions (FGS) were moderated on-site at nine pediatric practices. A semi
      structured topic guide was used to standardize and facilitate FGS. Discussions
      were audiotaped, and transcriptions were used to develop themes. All authors
      reviewed and agreed on the resultant themes. RESULTS: FGS included 13 physicians
      and 32 nurses/certified medical assistants (CMAs), of whom 82% personally
      conducted some facet of PVS. In all practices, nurses/CMAs tested visual acuity
      (most using a non-recommended test), and physicians completed vision screening
      with external observation, fix/follow, red reflex, and cover test. Facilitators
      included (1) accepting that PVS is a routine part of the well-child visit, and
      (2) using an electronic medical record with prompts to record acuity (eight of
      nine practices). Barriers were related to difficulty testing pre-schoolers,
      distractions in the office setting, time constraints, and limited reimbursement.
      CONCLUSIONS: Responsibility for PVS is shared by physicians and nurses/CMAs;
      thus, interventions to improve PVS should target both. Few practices are aware of
      new evidence-based PVS tests; thus, active translational efforts are needed to
      change current primary care practices.

PMID- 22982769
TI  - Smoking cessation and COPD mortality among Japanese men and women: the JACC
      study.
AB  - OBJECTIVE: To investigate an effect of smoking cessation on chronic obstructive
      pulmonary disease (COPD) mortality in Asians. METHODS: The data was obtained from
      the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study).
      A total of 41465 Japanese men and 52662 Japanese women aged 40-79 years who had
      no history of COPD, asthma, other chronic lung diseases, cardiovascular disease
      or cancer were followed between 1988 and 2008. RESULTS: During median 18-year of
      follow-up, there were 285 (251 men and 34 women) documented deaths from COPD.
      Multivariable-adjusted hazard ratios with 95% confidence intervals of COPD death
      were 4.46 (2.72-7.29) and 9.26 (4.19-20.5), respectively for current male and
      female smokers when compared to never smokers. Compared with current smokers, the
      multivariable HRs for 5-9 years and 10 years or more smoking cessation prior to
      baseline were 0.44 (0.22-0.87) and 0.36 (0.22-0.58) in men, respectively while
      the HR for never smokers was 0.30 (0.16-0.57). There were an insufficient number
      of COPD deaths in women to clarify this association. CONCLUSION: Smoking
      cessation for ten years or more prior to enrollment reverses the excess risk of
      COPD mortality to a level similar to that observed among never smokers in men.

PMID- 22982770
TI  - A modern in vivo pharmacokinetic paradigm: combining snapshot, rapid and full PK
      approaches to optimize and expedite early drug discovery.
AB  - Successful drug discovery relies on the selection of drug candidates with good in
      vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy
      and safety profiles. In vivo PK profiling is often a bottleneck in the discovery
      process. In this review, we focus on the tiered in vivo PK approaches implemented
      at the Genomics Institute of the Novartis Research Foundation (GNF), which
      includes snapshot PK, rapid PK and full PK studies. These in vivo PK approaches
      are well integrated within discovery research, allow tremendous flexibility and
      are highly efficient in supporting the diverse needs and increasing demand for in
      vivo profiling. The tiered in vivo PK studies expedite compound profiling and
      help guide the selection of more desirable compounds into efficacy models and for
      progression into development.

PMID- 22982771
TI  - Caffeic acid phenethyl ester ameliorates cadmium-induced kidney mitochondrial
      injury.
AB  - This study examined whether caffeic acid phenethyl ester (CAPE) can protect
      kidney mitochondria against cadmium toxicity. Kidney mitochondria isolated from
      Wistar rat were exposed to cadmium and/or CAPE at various concentrations.
      Mitochondrial function, ultrastructure and oxidative stress status were
      determined. Cadmium exposure resulted in mitochondrial swelling, dissipation of
      membrane potential, overproduction of reactive oxygen species, and impaired
      ultrastructure. The injury was accompanied by an increase in mitochondrial nitric
      oxide and malondialdehyde levels as well as a decrease in superoxide dismutase
      activity and antioxidant thiols. Pretreatment with CAPE ameliorated all the
      changes caused by cadmium. The results suggest a promising role for CAPE as
      mitochondria-targeted antioxidant to combat the renal toxicity of cadmium.

PMID- 22982772
TI  - Phenylalkyl isoselenocyanates vs phenylalkyl isothiocyanates: thiol reactivity
      and its implications.
AB  - Phenylalkyl isoselenocyanate (ISC) compounds were recently designed in our
      laboratory by incorporating the anticancer element selenium into a panel of
      phenylalkyl isothiocyanates (ITCs), known to have anticancer properties. A
      structural activity investigation was carried out to compare the ISC and ITC
      panels. Cell viability assay and Annexin V staining for apoptosis showed ISC
      compounds to be more potent in killing A549 lung adenocarcinoma cells. Both ITCs
      and ISCs were able to deplete reduced glutathione (GSH) in cells, ISCs more
      rapidly, but ITCs to a greater extent. ISC compounds had a higher rate of
      reaction to thiol (-SH) groups as determined by pseudo first order kinetics than
      the corresponding carbon chain length ITC. The equilibrium concentrations of the
      GSH and protein thiol conjugates did not differ significantly when comparing
      sulfur to selenium compounds of the same carbon chain length, and did follow the
      same trend of displaying decreasing reactivity with increasing carbon chain
      length for both ITCs and ISCs. Furthermore, only ITCs were able to induce cell
      cycle arrest, suggesting that protein targets inside the cell may differ for the
      S and Se panels. Finally, the panels were tested for their ability to redox cycle
      when reacted with GSH to form superoxide and other reactive oxygen species (ROS).
      ISC compounds showed a much greater ability to redox cycle than corresponding
      ITCs, and were able to induce higher levels of ROS in A549 cells. Also, the
      direct pro-apoptotic effects of ISCs and ITCs were inhibited by GSH and
      potentiated by depletion of intracellular GSH by buthionine sulfoximine. In
      conclusion, our studies suggest that the redox-cycling capabilities of ISCs and
      thus generation of higher levels of ROS may be contributing to the increased
      cytotoxicity of ISC compounds in A549 cells, compared to that of the
      corresponding ITCs.

PMID- 22982773
TI  - A common mechanism for resistance to oxime reactivation of acetylcholinesterase
      inhibited by organophosphorus compounds.
AB  - Administration of oxime therapy is currently the standard approach used to
      reverse the acute toxicity of organophosphorus (OP) compounds, which is usually
      attributed to OP inhibition of acetylcholinesterase (AChE). Rate constants for
      reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and
      obidoxime, can vary >100-fold between OP-AChE conjugates that are easily
      reactivated and those that are difficult to reactivate. To gain a better
      understanding of this oxime specificity problem for future design of improved
      reactivators, we conducted a QSAR analysis for oxime reactivation of AChE
      inhibited by OP agents and their analogues. Our objective was to identify common
      mechanism(s) among OP-AChE conjugates of phosphates, phosphonates and
      phosphoramidates that result in resistance to oxime reactivation. Our evaluation
      of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl
      isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl
      cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues
      was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or
      cyclosarin. In addition, AChE inhibited by an analogue of tabun (i.e., O-ethyl
      isopropylphosphonofluoridate) was nearly as resistant to reactivation as tabun
      inhibited AChE. QSAR analysis of oxime reactivation of AChE inhibited by these OP
      compounds and others suggested that the presence of both a large substituent
      (i.e., >= the size of dimethylamine) and an alkoxy substituent in the structure
      of OP compounds is the common feature that results in resistance to oxime
      reactivation of OP-AChE conjugates whether the OP is a phosphate, phosphonate or
      phosphoramidate.

PMID- 22982774
TI  - Pregnane X receptor mediated-transcription regulation of CYP3A by glycyrrhizin: a
      possible mechanism for its hepatoprotective property against lithocholic acid
      induced injury.
AB  - Licorice (LE) has been commonly used in traditional Chinese medicine (TCM) for
      over 4000 years to reconcile various drugs and for hepatic disorders.
      Glycyrrhizin is the main bioactive component isolated from LE herbs. In the
      present study we examined the effects of glycyrrhizin on pregnane X receptor
      (PXR)-mediated CYP3A expression and its hepatoprotective activity. Treatment of
      HepG2 cells with glycyrrhizin resulted in marked increase in both CYP3A4 mRNA and
      protein levels. The transcriptional activation of the CYP3A4 gene through
      glycyrrhizin is PXR-dependent, as shown in transient transfection experiments.
      Glycyrrhizin activates the DNA-binding capacity of the PXR for the CYP3A4 element
      responding to xenobiotic signals, as measured by the electrophoretic-mobility
      shift assay (EMSA). These results indicate that the induction of the hepatic
      CYP3A4 by glycyrrhizin is mediated through the activation of PXR. The next aim of
      the current study was to determine whether the activation of PXR and induction of
      CYP3A by glycyrrhizin prevents hepatotoxicity during cholestasis as a mechanism
      of hepatoprotection. Mice were pretreated with glycyrrhizin prior to induction of
      intrahepatic cholestasis using lithocholic acid (LCA). Pre-treatment with
      glycyrrhizin, as well as the PXR activator pregnenolone 16alpha-carbontrile
      (PCN), prevents the increase in plasma ALT and AST activity, multifocal necrosis
      and prevents an increase in a level of serum LCA level in mice, as compared with
      the results in the mice treated with LCA alone. Activation of the PXR by
      glycyrrhizin results in induction of CYP3A11 (CYP3A4 for human) expression and
      inhibition of CYP7A1 through an increase in small heterodimer partner (SHP)
      expression. Glycyrrhizin regulates the expression of the gene mentioned above to
      prevent toxic accumulation of bile acids in the liver and it also protects mouse
      livers from the harmful effects of LCA. In conclusion, PXR-mediated effects on
      CYP3A and CYP7A may contribute to the hepatoprotective property of glycyrrhizin
      against LCA-induced liver injury.

PMID- 22982775
TI  - On quantum mechanical--molecular mechanical (QM/MM) approaches to model
      hydrolysis of acetylcholine by acetylcholinesterase.
AB  - We re-visited the results of quantum mechanics--molecular mechanics (QM/MM)
      approaches aiming to construct the reaction energy profile for the acylation
      stage of acetylcholine hydrolysis by acetylcholinesterase. The main emphasis of
      this study was on the energy of the first tetrahedral intermediate (TI) relative
      to the level of the enzyme-substrate (ES) complex for which contradictory data
      from different works had been reported. A new series of stationary points on the
      potential energy surface was calculated by using electronically embedding QM/MM
      schemes when starting from the crystal structure mimicking features of the
      reaction intermediate (PDB ID: 2VJA). A thoughtful analysis allows us to conclude
      that the energy of TI should be lower than that of ES, and a proper treatment of
      contributions from the oxyanion hole residues accounts for their relative
      positions.

PMID- 22982776
TI  - Persistent and high-level expression of human liver prolidase in vivo in mice
      using adenovirus.
AB  - Human liver prolidase, a metal-dependent dipeptidase, is being tested as a
      potential catalytic bioscavenger against organophosphorus (OP) chemical warfare
      nerve agents. The purpose of this study was to determine whether persistent and
      high-levels of biologically active and intact recombinant human (rHu) prolidase
      could be introduced in vivo in mice using adenovirus (Ad). Here, we report that a
      single intravenous injection of Ad containing the prolidase gene with a 6*
      histidine-tag (Ad-prolidase) introduced high-levels of rHu prolidase in the
      circulation of mice which peaked on days 5-7 at 159 +/- 129 U/mL. This level of
      prolidase is ~120 times greater than that of the enzyme level in mice injected
      with Ad-null virus. To determine if all of Ad-prolidase-produced rHu prolidase
      was exported into the circulation, enzyme activity was measured in a variety of
      tissues. Liver contained the highest levels of rHu prolidase on day 7 (5647 +/-
      454 U/g) compared to blood or any other tissue. Recombinant Hu prolidase
      hydrolyzed DFP, a simulant of OP nerve agents, in vitro. In vivo, prolidase
      overexpression extended the survival of 4 out of 6 mice by 4-8h against exposure
      to two 1* LD(50) doses of DFP. In contrast, overexpression of mouse
      butyrylcholinesterase (BChE), a proven stoichiometric bioscavenger of OP
      compounds, protected 5 out of 6 mice from DFP lethality and surviving mice showed
      no symptoms of DFP toxicity. In conclusion, the results suggest that gene
      delivery using Ad is capable of introducing persistent and high levels of human
      liver prolidase in vivo. The gene-delivered prolidase hydrolyzed DFP in vitro but
      provided only modest protection in vivo in mice, delaying the death of the
      animals by only 4-8h.

PMID- 22982777
TI  - Purified mulberry leaf lectin (MLL) induces apoptosis and cell cycle arrest in
      human breast cancer and colon cancer cells.
AB  - Medicinal values of mulberry are known to humans from ancient ages. The white
      mulberry, Morus alba L. is a rich source of many bioactive phytochemicals.
      Earlier investigations in our laboratory lead to the purification and
      characterization of an anti-proliferative lectin (MLL) from the leaves of this
      plant. Further to that, here we have investigated the mechanism of cell death
      induction by MLL on human breast cancer (MCF-7) and colon cancer (HCT-15) cells.
      Cells were treated with GI(50) concentration (concentration of lectin required
      for 50% inhibition of cell growth) of MLL (8.5 MUg/ml for MCF-7 and 16 MUg/ml for
      HCT-15) for 24 h to induce cell death. The induction of apoptosis was studied by
      morphological analysis, DNA fragmentation, apoptotic cell staining and caspase 3
      activity assay. Apoptotic cells in sub G0-G1 phase were monitored using flow
      cytometry. MLL induced significant morphological changes and DNA fragmentation
      associated with apoptosis in MCF-7 and HCT-15 cells. Positive annexin V and
      acridine orange/ethidium bromide stained cells indicated apoptosis induction by
      MLL. Up-regulation of caspase 3 activity was also found in cells treated with
      MLL. Flow cytometry analysis showed an increase in the percentage of cells in sub
      G0-G1 phase confirming the MLL induced apoptosis. In conclusion, MLL induced
      apoptosis in MCF-7 and HCT-15 cells in a caspase dependent manner.

PMID- 22982778
TI  - Preconditioning protects the heart in a prolonged uremic condition.
AB  - Metabolic diseases such as hyperlipidemia and diabetes attenuate the
      cardioprotective effect of ischemic preconditioning. In the present study, we
      examined whether another metabolic disease, prolonged uremia, affects
      ischemia/reperfusion injury and cardioprotection by ischemic preconditioning.
      Uremia was induced by partial nephrectomy in male Wistar rats. The development of
      uremia was verified 29 wk after surgery. Transthoracic echocardiography was
      performed to monitor cardiac function. At week 30, hearts of nephrectomized and
      sham-operated rats were isolated and subjected to a 30-min coronary occlusion
      followed by 120 min reperfusion with or without preceding preconditioning induced
      by three intermittent cycles of brief ischemia and reperfusion. In nephrectomized
      rats, plasma uric acid, carbamide, and creatinine as well as urine protein levels
      were increased as compared with sham-operated controls. Systolic anterior and
      septal wall thicknesses were increased in nephrectomized rats, suggesting the
      development of a minimal cardiac hypertrophy. Ejection fraction was decreased and
      isovolumic relaxation time was shortened in nephrectomized rats demonstrating a
      mild systolic and diastolic dysfunction. Infarct size was not affected
      significantly by nephrectomy itself. Ischemic preconditioning significantly
      decreased infarct size from 24.8 +/- 5.2% to 6.6 +/- 1.3% in the sham-operated
      group and also in the uremic group from 35.4 +/- 9.5% to 11.9 +/- 3.1% of the
      area at risk. Plasma ANG II and nitrotyrosine were significantly increased in the
      uremic rats. We conclude that although prolonged experimental uremia leads to
      severe metabolic changes and the development of a mild myocardial dysfunction,
      the cardioprotective effect of ischemic preconditioning is still preserved.

PMID- 22982779
TI  - Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by
      anisomycin.
AB  - Transient activation of p38 through anisomycin is demonstrated to precondition
      the heart against myocardial injury. However, it remains unknown whether specific
      TNF-alpha receptor (TNFR) p55/p75 and Nox2, a subunit of NADPH oxidase, are
      involved in this event. We sought to investigate whether the genetic disruption
      of TNFRp55/p75 and Nox2 eliminated cardioprotection elicited by anisomycin and
      whether p38-dependent activation of Nox2 stimulated TNFR to ultimately achieve
      protective effects. Adult wild-type and TNFR p55/p75(-/-) and Nox2(-/-) mice
      received intraperitoneal injections of anisomycin (0.1 mg/kg), a potent activator
      of p38. The hearts were subjected to 30 min myocardial ischemia/30 min
      reperfusion in the Langendorff perfused heart after 24 h. Left ventricular
      function was measured, and infarct size was determined. Myocardial TNF-alpha
      protein, Nox2, and superoxides releases were detected. Gel kinase assay was
      employed to detect the effect of p38 on Nox2 phosphorylation. Activation of p38
      through anisomycin produces marked improvements in left ventricular functional
      recovery, and the reduction of myocardial infarction, which were abrogated by
      disruption of Nox2 and TNFR p55/p75. Disruption of Nox2 and TNFR p55/p75
      abolished the effect of anisomycin-induced reduction of infarct size. Anisomycin
      induced the production of TNF-alpha, which was abrogated in Nox2(-/-) mice and by
      treatment with SB203580, but not by disruption of p55/p75. Anisomycin treatment
      resulted in an increase in Nox2 protein and the phosphorylation of Nox2, which
      was blocked by inhibition of p38. Taken together, these results indicate that
      stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to
      anisomycin-induced cardioprotection.

PMID- 22982781
TI  - Cross talk between S-nitrosylation and S-glutathionylation in control of the Na,K
      ATPase regulation in hypoxic heart.
AB  - Oxygen-induced regulation of Na,K-ATPase was studied in rat myocardium. In rat
      heart, Na,K-ATPase responded to hypoxia with a dose-dependent inhibition in
      hydrolytic activity. Inhibition of Na,K-ATPase in hypoxic rat heart was
      associated with decrease in nitric oxide (NO) production and progressive
      oxidative stress. Accumulation of oxidized glutathione (GSSG) and decrease in NO
      availability in hypoxic rat heart were followed by a decrease in S-nitrosylation
      and upregulation of S-glutathionylation of the catalytic alpha-subunit of the
      Na,K-ATPase. Induction of S-glutathionylation of the alpha-subunit by treatment
      of tissue homogenate with GSSG resulted in complete inhibition of the enzyme in
      rat a myocardial tissue homogenate. Inhibitory effect of GSSG in rat sarcolemma
      could be significantly decreased upon activation of NO synthases. We have further
      tested whether oxidative stress and suppression of the Na,K-ATPase activity are
      observed in hypoxic heart of two subterranean hypoxia-tolerant blind mole species
      (Spalax galili and Spalax judaei). In both hypoxia-tolerant Spalax species
      activity of the enzyme and tissue redox state were maintained under hypoxic
      conditions. However, localization of cysteines within the catalytic subunit of
      the Na,K-ATPase was preserved and induction of S-glutathionylation by GSSG in
      tissue homogenate inhibited the Spalax ATPase as efficiently as in rat heart. The
      obtained data indicate that oxygen-induced regulation of the Na,K-ATPase in the
      heart is mediated by a switch between S-glutathionylation and S-nitrosylation of
      the regulatory thiol groups localized at the catalytic subunit of the enzyme.

PMID- 22982780
TI  - Sex differences in mesenteric endothelial function of streptozotocin-induced
      diabetic rats: a shift in the relative importance of EDRFs.
AB  - Several studies suggest that diabetes affects male and female vascular beds
      differently. However, the mechanisms underlying the interaction of sex and
      diabetes remain to be investigated. This study investigates whether there are 1)
      sex differences in the development of abnormal vascular responses and 2) changes
      in the relative contributions of endothelium-derived relaxing factors in
      modulating vascular reactivity of mesenteric arteries taken from streptozotocin
      (STZ)-induced diabetic rats at early and intermediate stages of the disease (1
      and 8 wk, respectively). We also investigated the mesenteric expression of the
      mRNAs for endothelial nitric oxide (NO) synthase (eNOS) and NADPH oxidase (Nox)
      in STZ-induced diabetes in both sexes. Vascular responses to acetylcholine (ACh)
      in mesenteric arterial rings precontracted with phenylephrine were measured
      before and after pretreatment with indomethacin (cyclooxygenase inhibitor),
      N(omega)-nitro-L-arginine methyl ester (NOS inhibitor), or barium chloride (K(ir)
      blocker) plus ouabain (Na(+)-K(+)-ATPase inhibitor). We demonstrated that ACh
      induced relaxations were significantly impaired in mesenteric arteries from both
      male and female diabetic rats at 1 and 8 wk. However, at 8 wk the extent of
      impairment was significantly greater in diabetic females than diabetic males. Our
      data also showed that in females, the levels of eNOS, Nox2, and Nox4 mRNA
      expression and the relative importance of NO to the regulation of vascular
      reactivity were substantially enhanced, whereas the importance of endothelium
      derived hyperpolarizing factor (EDHF) was significantly reduced at both 1 and 8
      wk after the induction of diabetes. This study reveals the predisposition of
      female rat mesenteric arteries to vascular injury after the induction of diabetes
      may be due to a shift away from a putative EDHF, initially the major vasodilatory
      factor, toward a greater reliance on NO.

PMID- 22982783
TI  - Necessity for long-term follow-up of patients with head and neck paraganglioma
      and mutation in the succinate dehydrogenase genes: an index case report and
      literature review.
AB  - OBJECTIVE: To describe a patient with hereditary head and neck paraganglioma
      (HNPGL) and to review the literature on these rare tumors. METHODS: We review the
      English-language literature regarding SDH mutations, HNPGL, hereditary
      paraganglioma-pheochromocytoma syndrome, and the role of functional imaging in
      the follow-up of these tumors. We also describe the clinical findings, imaging
      results, and follow-up of a man who initially presented with HNPGL and
      subsequently developed metastatic pheochromocytoma 20 years later. RESULTS: A 66
      year-old man presented with a history of hypertension, palpitations, sweating,
      and elevated urinary norepinephrine. Iodine-123-metaiodobenzylguanidine (123I
      MIBG) scan demonstrated a left suprarenal mass and multiple avid lesions in the
      abdomen, chest, and posterior cranial fossa. Histologic examination confirmed a
      metastatic pheochromocytoma, and molecular genetic testing revealed a mutation in
      the SDHD gene. The patient had had surgery 20 years earlier for HNPGL. Although
      most HNPGLs arise sporadically, susceptibility genes have been identified in
      approximately one-third of cases. Optimal follow-up remains controversial. We
      reiterate a need for long-term follow-up of patients with a mutation in an SDH
      gene. 123I-MIBG, highly specific for identifying ectopic neuroendocrine tissue,
      may have a role in long-term follow-up. CONCLUSIONS: Although HNPGLs rarely
      metastasize, their malignant potential is difficult to predict. Routine
      surveillance for at-risk patients is recommended. Patients with a mutation in an
      SDH gene should therefore undergo regular surveillance.

PMID- 22982782
TI  - Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation.
AB  - Fibrosis following myocardial infarction is associated with increases in
      arrhythmias and sudden cardiac death. Initial steps in the development of
      fibrosis are not clear; however, it is likely that cardiac fibroblasts play an
      important role. In immune cells, ATP release from pannexin 1 (Panx1) channels
      acts as a paracrine signal initiating activation of innate immunity. ATP has been
      shown in noncardiac systems to initiate fibroblast activation. Therefore, we
      propose that ATP release through Panx1 channels and subsequent fibroblast
      activation in the heart drives the development of fibrosis in the heart following
      myocardial infarction. We identified for the first time that Panx1 is localized
      within sarcolemmal membranes of canine cardiac myocytes where it directly
      interacts with the postsynaptic density 95/Drosophila disk large/zonula occludens
      1-containing scaffolding protein synapse-associated protein 97 via its carboxyl
      terminal domain (amino acids 300-357). Induced ischemia rapidly increased
      glycosylation of Panx1, resulting in increased trafficking to the plasma membrane
      as well as increased interaction with synapse-associated protein 97. Cellular
      stress enhanced ATP release from myocyte Panx1 channels, which, in turn, causes
      fibroblast transformation to the activated myofibroblast phenotype via activation
      of the MAPK and p53 pathways, both of which are involved in the development of
      cardiac fibrosis. ATP release through Panx1 channels in cardiac myocytes during
      ischemia may be an early paracrine event leading to profibrotic responses to
      ischemic cardiac injury.

PMID- 22982784
TI  - Clinical outcomes of concomitant therapy of exenatide twice daily and basal
      insulin in patients with type 2 diabetes mellitus: a retrospective database
      analysis in the United States.
AB  - OBJECTIVE: To examine the clinical effectiveness of concomitant therapy of
      exenatide twice daily and basal insulin in patients with type 2 diabetes mellitus
      in the United States. METHODS: Data from adults with type 2 diabetes were
      selected from an electronic medical record database. Concomitant therapy was
      defined as a basal insulin prescription within 6 months before or after an
      exenatide prescription between May 2005 and April 2009. Upon initiation, patients
      were treated with both medications. Clinical effectiveness was measured as mean
      changes in hemoglobin A1c (primary outcome), body weight, body mass index, blood
      pressure, and lipid values from a 6-month baseline to mean-adjusted values in a
      12-month follow-up period. These changes were assessed by a bootstrapping test.
      RESULTS: There were 1752 patients (mean age, 57 years) who initiated concomitant
      therapy (75% added exenatide to basal insulin, 25% added basal insulin to
      exenatide). Patients achieved significant mean reductions in hemoglobin A1c
      (0.5%), body weight (1.8 kg), body mass index (0.6 kg/m2), diastolic blood
      pressure (0.5 mm Hg), and various lipid measures (all P<.05). Hemoglobin A1c
      reduction was consistent irrespective of the treatment order. However, body
      weight, body mass index, and blood pressure reductions were observed in only
      patients who added exenatide to basal insulin. CONCLUSIONS: Overall, exenatide
      and basal insulin concomitant therapy was associated with significant reductions
      in hemoglobin A1c, body weight, body mass index, diastolic blood pressure, and
      lipids in a large, diverse patient population treated in ambulatory care settings
      in the United States. In the subgroup analysis, body weight, body mass index, and
      diastolic blood pressure reductions were observed in only patients who added
      exenatide to basal insulin.

PMID- 22982785
TI  - Feasibility of immediate assessment of fine needle aspirates of thyroid nodules
      by telecytopathology.
AB  - OBJECTIVE: In this study we discuss the diagnostic accuracy and unsatisfactory
      rate of onsite evaluation of ultrasound-guided fine needle aspiration (USGFNA) of
      thyroid nodules using telecytopathology and compare it to that of a control group
      without telecytopathology. METHODS: This was a retrospective analysis of USGFNA
      of thyroid nodules over a 9-month period with and without telecytopathology.
      There was no randomization for selection of the groups with and without
      telepathologist. A single provider performed all the procedures. Real-time images
      of Diff Quik-stained cytology smears were obtained with an Olympus Digital camera
      attached to an Olympus CX41 microscope and transmitted via the Internet by a
      cytotechnologist to a pathologist, who communicated the preliminary diagnosis and
      sample adequacy. The unsatisfactory specimen rate was compared between a group
      whose images were transmitted (n = 45) and another group without onsite adequacy
      assessment (nontransmitted) (n = 47). RESULTS: A total of 92 nodules in 67
      patients were aspirated with ultrasound guidance. The unsatisfactory sample rate
      in the transmitted group was 13% (6 out of 45) and that of the non-transmitted
      group was 23% (11 out of 47). In the transmitted group, the cytology specimens of
      3 patients that were initially deemed inadequate by the pathologist were
      considered adequate after 2 additional passes. In the transmitted group,
      preliminary diagnosis concurred with the final diagnosis in 96% of cases. Four
      passes were made in the non-transmitted group, versus 2 passes in the transmitted
      group. CONCLUSION: Immediate assessment of USGFNA via telecytopathology assures
      adequacy of the cytology sample and may reduce number of passes per nodule.
      Preliminary onsite telecytopathology diagnosis was highly accurate when compared
      to final diagnosis.

PMID- 22982786
TI  - Unchanged serum adipokine concentrations in the setting of short-term
      thyroidectomy-induced hypothyroidism.
AB  - OBJECTIVE: To investigate short-term effects of thyroidectomy-induced
      hypothyroidism on leptin, adiponectin, and resistin concentrations in association
      with anthropometric data. METHODS: Thirty premenopausal women with euthyroid
      nodular goiter-mean age, 44.0 +/- 11.6 years; mean body mass index (BMI), 28.6 +/
      5.9 kg/m2; 13 obese, 7 overweight, and 10 normal weight subjects-scheduled for
      total thyroidectomy were included in the study. Serum leptin, adiponectin,
      resistin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone,
      glucose, insulin, and C-reactive protein concentrations, lipid profile, and
      anthropometric variables were determined in the euthyroid state (preoperatively)
      and the hypothyroid state (postoperatively, with a thyroid-stimulating hormone
      concentration >30 mIU/L). RESULTS: Body weight, BMI, waist and hip
      circumferences, body fat mass, and serum lipid concentrations increased
      significantly after thyroidectomy. No significant difference was found between
      preoperative and postoperative serum leptin, adiponectin, and resistin
      concentrations. Fat tissue mass-corrected leptin, adiponectin, and resistin
      concentrations did not differ significantly between euthyroid and hypothyroid
      periods. Thyroid hormone concentrations showed no significant correlations with
      adipokine levels. CONCLUSION: Serum adipokine concentrations seem not to change
      significantly during short-term thyroidectomy-induced hypothyroidism despite
      significant increases in body weight, BMI, fat mass, and lipid concentrations.

PMID- 22982787
TI  - Significant attenuation of stimulated cortisol in early Graves disease without
      adrenal autoimmunity.
AB  - OBJECTIVE: To investigate cortisol responses to adrenocorticotropic hormone
      during thyrotoxic (G1) and euthyroid (G2) phases in patients with Graves disease
      (GD) who were without adrenal autoimmunity. METHODS: Fifteen patients with GD,
      who were thyrotropin receptor antibody positive and 21-hydroxylase antibody
      negative, were recruited to this prospective pilot study. A modified short
      Synacthen test (SST) was performed, in which cortisol was measured every 30
      minutes for 2 hours during G1 and G2. RESULTS: The median times to SST were 3
      weeks (G1) and 27 weeks (G2) after diagnosis of GD. Integrated stimulated
      cortisol levels were significantly lower at G1 in comparison with G2: mean +/-
      standard error of the mean for area under the curve was 78,091.6 +/- 4,462.1
      nmol/L (G1) versus 89,055 +/- 4,434 nmol/L at 120 minutes (G2), P = .017; and for
      delta area under the curve was 36,309.9 +/- 3,526 nmol/L (G1) versus 44,041.7 +/-
      2,147 nmol/L at 120 minutes (G2), P = .039. Mean cortisol levels were
      significantly lower for G1 versus G2 at 60, 90, and 120 minutes of the SST (P =
      .001 to .013). The cortisol level was abnormal in 2 patients (13%) at 30 minutes
      during G1 but in none during G2. There was no correlation of integrated cortisol
      with free thyroxine or thyrotropin receptor antibody. There was no significant
      difference in median adrenocorticotropic hormone level (17 versus 20.4 ng/mL at
      G1 and G2, respectively; P = .14). CONCLUSION: Significant attenuation of
      stimulated cortisol occurs in the early thyrotoxic phase in comparison with the
      euthyroid phase in patients with GD without adrenal autoimmunity. Clinicians
      treating patients with GD should have a low threshold for investigating symptoms
      suggestive of hypoadrenalism at times of "stress."

PMID- 22982788
TI  - Safety and feasibility of laparoscopic resection for large (>= 6 CM)
      pheochromocytomas without suspected malignancy.
AB  - OBJECTIVE: To determine whether laparoscopic adrenalectomy in patients without
      radiologic evidence of cancer compromises the perioperative and long-term
      outcomes in patients with large (>= 6 cm) pheochromocytomas. METHODS: We analyzed
      a prospective adrenal database of consecutive patients who underwent
      adrenalectomy at our institution between September 2000 and September 2010.
      Patients with diagnosed pheochromocytoma who underwent laparoscopic adrenalectomy
      were included. Patients with tumors smaller than 6 cm were compared with those
      presenting with tumors 6 cm or larger. RESULTS: One hundred fifty-seven patients
      underwent adrenalectomy, and there were 32 catecholamine-secreting tumors. Of the
      33, 7 were excluded from the study because of open surgery. Thus, 25 patients
      presented with 26 pheochromocytomas and underwent laparoscopic adrenalectomy.
      Thirteen of the 25 patients (52%) were women. Mean age (+/- standard error of the
      mean) was 53 +/- 3 years. Mean tumor size was 5.2 +/- 0.5 cm, and 11
      pheochromocytomas (42%) were 6 cm or larger. Tumor size was significantly
      different between the large pheochromocytoma and the small pheochromocytoma
      groups (7.6 +/- 0.4 vs 3.6 +/- 0.4 cm, P<.001), but there was no significant
      difference in intraoperative complications, estimated blood loss, cancer
      diagnosis, or recurrence. The length of stay was comparable between the 2
      cohorts, and there were no incidents of capsular invasion or adverse
      cardiovascular events. CONCLUSION: Laparoscopic adrenalectomy of
      pheochromocytomas larger than 6 cm is feasible and safe with comparable results
      to those achieved with laparoscopic adrenalectomy in patients with smaller
      pheochromocytomas.

PMID- 22982789
TI  - Changes in thyroid function in Ethiopian and non-Ethiopian Israeli patients with
      human immunodeficiency virus infection or acquired immunodeficiency syndrome.
AB  - OBJECTIVE: To investigate whether human immunodeficiency virus (HIV) infection or
      its treatment is a risk factor for thyroid dysfunction and whether thyroid
      function changes over time in 2 distinct subpopulations with HIV or acquired
      immunodeficiency syndrome (AIDS) in Israel: Ethiopian immigrants and Israeli
      patients. METHODS: Serum thyroid-stimulating hormone (TSH) and free thyroxine
      levels were determined in HIV carriers undergoing follow-up at the Hadassah
      Hebrew University Medical Center HIV clinic in Jerusalem, Israel, and these
      thyroid measurements were correlated with clinical and laboratory variables
      pertaining to their disease, including disease duration, drug therapy, viral
      load, CD4 count, low-density lipoprotein cholesterol, and creatine kinase. Serum
      samples stored at -20 degrees C from the time of referral were tested as well.
      RESULTS: We recruited 121 consecutive patients with HIV or AIDS for this study:
      60 Ethiopians and 61 Israeli patients. Of the 121 patients, 4 (3%) had abnormal
      thyroid function-subclinical hypothyroidism in 2, overt hypothyroidism in 1, and
      overt hyperthyroidism in 1. Previously stored serum samples were available for 60
      of the 121 patients and revealed 2 additional patients with subclinical
      hypothyroidism, whose TSH has normalized in the subsequent test. Throughout the
      follow-up period of 3.2 +/- 1.9 years, the mean TSH level remained unchanged in
      the Israeli cohort but significantly declined in the Ethiopian cohort.
      CONCLUSION: Thyroid function abnormalities were uncommon in these Israeli
      patients with HIV or AIDS. This finding does not support the need for routine
      thyroid function tests in this patient population. The decline in TSH level in
      the Ethiopian population over time probably represents a shift from an iodine
      deficient to an iodine-sufficient country.

PMID- 22982790
TI  - Performance of plasma fractionated free metanephrines by enzyme immunoassay in
      the diagnosis of pheochromocytoma and paraganglioma in children.
AB  - OBJECTIVE: To establish pediatric reference ranges for plasma fractionated free
      metanephrines by enzyme immunoassay (EIA) and to evaluate its performance in the
      diagnosis of catecholamine-secreting tumors in the pediatric population. METHODS:
      Normotensive children and children with suspected catecholamine-secreting tumors
      underwent measurement of plasma fractionated metanephrines by EIA to establish
      pediatric reference ranges. Children with suspected pheochromocytoma or
      paraganglioma also underwent magnetic resonance imaging or computed tomography
      from the neck to the pelvis and were followed up for a minimum of 1 year.
      Diagnosis of pheochromocytoma/paraganglioma was confirmed by histologic
      examination. Pheochromocytoma/paraganglioma was excluded in children who had a
      histologic diagnosis other than pheochromocytoma/paraganglioma and in those who
      had no imaging evidence of tumor and no progression on follow-up. RESULTS: Plasma
      fractionated metanephrines were measured in 78 normotensive children (age range,
      1.5-17 years) and in 38 children with suspected catecholamine-secreting tumors.
      Of the 38 children (age range, 6-17 years) with suspected
      pheochromocytoma/paraganglioma, 17 had a histopathologically proven catecholamine
      secreting tumor. The newly derived pediatric upper reference limit for
      metanephrine (128 pg/mL) was higher than in adults (90 pg/mL), whereas the
      pediatric upper reference limit for normetanephrine (149 pg/mL) was lower than in
      adults (180 pg/mL). The manufacturer's reference range for plasma fractionated
      metanephrines yielded a sensitivity of 100% and a specificity of 85.7%. Use of
      newly established pediatric reference ranges increased the specificity to 95.2%
      without altering the sensitivity (100%). CONCLUSIONS: Plasma fractionated
      metanephrines by EIA provide an accurate test with good sensitivity and
      specificity for the diagnosis of pheochromocytoma and paraganglioma in children.
      Use of pediatric reference ranges improves accuracy of the test.

PMID- 22982791
TI  - Danger of hypoglycemia due to acute tramadol poisoning.
AB  - OBJECTIVE: To report a case of prolonged hypoglycemia after acute tramadol
      poisoning. METHODS: We describe a patient's clinical presentation and outcome
      with prolonged hypoglycemia attributable to acute tramadol poisoning. In
      addition, the possible mechanism for the hypoglycemia is discussed, and a brief
      review of the pertinent literature is presented. RESULTS: A 54-year-old woman had
      previously undergone a partial hepatectomy because of involvement of her liver by
      a gastrointestinal stromal tumor. After ingestion of 3,000 mg of tramadol with
      suicidal intent, she developed prolonged hypoglycemia that necessitated treatment
      with continuous intravenous glucose infusion for 24 hours. Reports in the
      literature have described central nervous system depression, nausea, vomiting,
      tachycardia, seizures, and even death from tramadol overdoses. CONCLUSION: This
      report alerts clinicians to the potential danger of severe hypoglycemia in
      tramadol poisoning.

PMID- 22982793
TI  - Mucocolpos in a toddler: central precocious puberty with vaginal atresia.
AB  - OBJECTIVE: To report the first case of imperforate hymen and vaginal atresia in a
      patient with mucocolpos during toddlerhood who was found to have central
      precocious puberty. METHODS: We review the details of assessment of an 18-month
      old girl who had the presence of pubic hair and breast enlargement. She underwent
      biochemical evaluation with serum follicle-stimulating hormone, luteinizing
      hormone, and estradiol and radiologic evaluation with ultrasonography of the
      abdomen and pelvis as well as magnetic resonance imaging of the pelvis and brain.
      RESULTS: This young female patient had clinical and imaging findings suggestive
      of idiopathic central precocious puberty. Imaging also revealed imperforate
      hymen, vaginal atresia, and mucocolpos. She underwent surgical treatment to
      ensure an unobstructed vaginal opening before initiation of gonadotropin
      releasing hormone agonist therapy, since the latter may precipitate uterine
      bleeding and might have converted mucocolpos to a combination of mucocolpos and
      hematocolpos. CONCLUSION: This case highlights the need to suspect the presence
      of precocious puberty in all female patients in whom mucocolpos is detected
      beyond infancy but before adolescence.

PMID- 22982792
TI  - Prevalence and predictors of vitamin D deficiency in healthy adults.
AB  - OBJECTIVE: Vitamin D deficiency is highly prevalent in high-risk patient
      populations, but the prevalence among otherwise healthy adults is less well
      defined. The goal of this study was to determine the prevalence and predictors of
      low 25-hydroxyvitamin D [25(OH)D] levels in healthy younger adults. METHODS: This
      was a cross-sectional study of 634 healthy volunteers aged 18-50 years performed
      between January, 2006 and May, 2008. We measured serum 25(OH)D and parathyroid
      hormone and recorded demographic variables including age, sex, race, and use of
      multivitamin supplements. RESULTS: Thirty-nine percent of subjects had 25(OH)D <=
      20 ng/mL and 64% had 25(OH)D <= 30 ng/mL. Predictors of lower 25(OH)D levels
      included male sex, black or Asian race, and lack of multivitamin use (P<0.001 for
      each predictor). Seasonal variation in 25(OH)D levels was present in the overall
      cohort but was not observed in multivitamin users. Lower 25(OH)D levels were
      associated with increased risk of elevated parathyroid hormone. Regression models
      predicted 25(OH)D levels <= 20 or <= 30 ng/mL with areas under the receiver
      operating characteristic curves of 0.76 and 0.80, respectively. CONCLUSION: Low
      25(OH)D levels are prevalent in healthy adults and may confer risk of skeletal
      disease. Black and Asian adults are at increased risk of deficiency and
      multivitamin use appears partially protective. Our models predicting low 25(OH)D
      levels may guide decision-making regarding whom to screen for vitamin D
      deficiency.

PMID- 22982794
TI  - Use of insulin pump therapy in patients with type 2 diabetes after failure of
      multiple daily injections.
AB  - OBJECTIVE: To determine the effectiveness of insulin pump use (continuous
      subcutaneous insulin infusion; CSII) in patients with type 2 diabetes (DM2) who
      have failed multiple daily injection (MDI) therapy. METHODS: In this
      retrospective study, charts of patients with DM2 who were started on CSII after
      failure of MDI were reviewed. Patients were categorized as primarily manual
      (fixed) bolus users or calculated (using pump software) bolus users. The change
      in hemoglobin A1c (HbA1c), weight, and basal insulin dose from baseline to 6
      months was determined. RESULTS: Fifty-seven patients (20 men and 37 women)
      ranging in age from 13 to 71 were identified in the study. A significant
      reduction in HbA1c was observed from 8.75 to 7.69% (P<.001). There was an
      increase in body mass index (BMI) from a mean of 36.53 to a mean of 37.21. A
      decrease in basal insulin requirement per kilogram of weight (-0.10 U/kg) was
      noted (P = .03). Seven patients using U-500 insulin in the pump also had a
      significant decrease in HbA1C of 1.1 % (P<.001), along with a 0.071 U/kg drop in
      basal insulin requirements (P<.001). When comparing calculated bolus users to
      manual bolus users, there was no difference in HbA1C improvement (P = .58).
      CONCLUSION: We found that CSII improves glucose control in patients with DM2 who
      have failed MDI despite a decrease in overall insulin requirements. This includes
      patients with severe insulin resistance using U-500 insulin. Use of frequent
      bolus adjustment incorporating carbohydrate counting and current glucose level
      does not appear to be required for this benefit.

PMID- 22982795
TI  - Apoplexy of a microprolactinoma during pregnancy: case report and review of
      literature.
AB  - OBJECTIVE: To report a rare case of apoplexy in a microprolactinoma during
      pregnancy. METHODS: We present the initial clinical manifestations, laboratory
      results, radiologic findings, and management in a patient who had pituitary
      apoplexy during early pregnancy. The pertinent literature and management options
      are also reviewed. RESULTS: A 37-year-old woman with a history of a
      microprolactinoma presented during the 16th week of her first pregnancy with a
      sudden onset of severe headache, nausea, vomiting, and blurred vision. Magnetic
      resonance imaging showed a sellar heterogeneous mass with suprasellar extension
      and contact with the optic chiasm, compatible with adenoma apoplexy. The
      patient's visual fields were normal. Conservative management was followed by
      rapid clinical improvement and a notable regression of the sellar mass after 5
      weeks of cabergoline therapy. Uneventful pregnancy resulted in the delivery of a
      healthy baby. Repeated magnetic resonance imaging was performed 1 week after
      delivery and showed resolution of the microadenoma. At 3 months after delivery,
      the patient had recovered regular menses and had sustained normal prolactin
      levels without treatment. CONCLUSION: This case illustrates a rare occurrence of
      apoplexy in a microprolactinoma during pregnancy, which was managed
      conservatively and led to a complete regression of the pituitary tumor.

PMID- 22982796
TI  - The association of newer anticonvulsant medications and bone mineral density.
AB  - OBJECTIVE: Previous studies have shown an association between the use of
      traditional anticonvulsants (e.g. phenytoin, carbamazepine, valproate) and
      decreased bone mineral density (BMD). However, there are limited data regarding
      the effects of newer anticonvulsants (e.g. gabapentin, levetiracetam, topiramate)
      on BMD. The aim of this study was to examine the association between the duration
      of anticonvulsant exposure and BMD, focusing on newer anticonvulsants. METHODS:
      This is a retrospective cohort study of patients at a single Veterans Affairs
      (VA) Medical Center. Longitudinal prescription histories, medical comorbidities,
      vital statistics, and BMD assessments by dual-energy X-ray absorptiometry (DXA),
      were abstracted from the computerized medical record. Among 1779 individuals with
      a DXA scan within the study period, 560 were prescribed at least one
      anticonvulsant. RESULTS: After adjusting for multiple confounders (including age,
      gender, body mass index, medical comorbidities, and other medication use), higher
      duration of use of newer, nonenzyme-inducing anticonvulsants was associated with
      a higher T-score at the total hip (0.05 standard deviations [SD], p = 0.02) and
      lumbar (0.10 SD, p < 0.01), compared to non-users referred for BMD assessment. In
      contrast, higher duration of use of traditional anticonvulsants had a lower total
      hip T-score. Furthermore, patients prescribed newer, nonenzyme-inducing
      anticonvulsants were less likely to have a diagnosis of osteoporosis at the
      lumbar spine (OR 0.80, 95% CI: 0.68 - 0.95), femoral neck (OR 0.82, 95% CI: 0.69 
      0.98), and total hip (OR 0.74, 95% CI: 0.56 - 0.98). CONCLUSION: The results
      suggest that newer anticonvulsant medications are not associated with lower BMD.

PMID- 22982797
TI  - Cancer with diabetes: prevalence, metabolic control, and survival in an academic
      oncology practice.
AB  - OBJECTIVE: To determine the prevalence of diabetes mellitus, glycemic control,
      and impact of diabetes on overall survival in an academic oncology practice.
      METHODS: Data on cancer patients (1999 to 2008) were retrieved from the
      institutional cancer registry and linked to electronic files to obtain diabetes
      status and hemoglobin A1c (A1C) values within the first 6 months of cancer
      diagnosis. Overall survival by cancer type with and without diabetes was compared
      using Cox regression. RESULTS: Excluding skin and hematologic malignancies,
      15,951 cancer cases were identified. Overall diabetes prevalence was 6.8% (n =
      1,090), declining over time (P<0.001). Diabetes was common among patients with
      pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder
      cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70
      versus 66 years; P<0.001) and more likely to be male (66.3% [723 of 1,090] versus
      60.2% [8,949 of 14,858]; P<0.001). The mean A1C among diabetic cancer patients
      was 6.8% and did not differ across cancer types (P = 0.80). Only 58.6% (331 of
      565) of diabetic cancer patients had all A1C <7.0% during the first 6 months
      following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes
      had better overall survival than pancreatic cancer patients without diabetes
      (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P<0.001). Conversely,
      diabetic prostate cancer patients had worse overall survival than prostate cancer
      patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to
      1.76; P = 0.02). CONCLUSION: In this academic oncology practice, diabetes was
      common, glycemic control often was suboptimal, and survival varied by cancer
      type. Additional study is needed to optimize glucose management and investigate
      mechanisms underlying age, sex, and survival differences.

PMID- 22982798
TI  - Hypothyroidism as a cause of hyponatremia: fact or fiction?
AB  - OBJECTIVE: To illustrate that severe primary hypothyroidism alone may not be
      enough to cause hyponatremia in the otherwise healthy ambulatory patient.
      METHODS: A retrospective chart review was conducted using an academic health
      center enterprise-wide electronic health record to identify 10 patients with
      primary hypothyroidism and same-day serum thyroid-stimulating hormone (TSH),
      sodium, creatinine, and calculated glomerular filtration rate (GFR). Same-day
      free triiodothyronine or free thyroxine was also recorded if tested. Patients
      were included in our case series if they met the following inclusion criteria:
      TSH level >100 MUU/mL and same-day sodium and creatinine levels. All laboratory
      tests were collected on an outpatient basis. RESULTS: The 10 subjects (2 men and
      8 women) were ages 19 to 97 years (median, 51.5 years). Median TSH was 193 MUU/mL
      (range, 104.2 to 515.6 MUU/mL; normal, 0.40 to 5.50 MUU/mL) with median sodium of
      138 mmol/L (range, 136 to 142 mmol/L; normal, 135 to 146 mmol/L). The lowest
      sodium was 136 mmol/L with concurrent TSH of 469.7 MUU/mL, free triiodothyronine
      of 1.0 pg/mL (normal, 1.8 to 4.6 pg/mL), and free thyroxine of 0.2 ng/dL (normal,
      0.7 to 1.8 ng/dL). Median GFR was 67.5 mL/min/1.73 m2 (range, 44 to 114
      mL/min/1.73 m2; normal, 90 to 120 mL/min/1.73 m2). CONCLUSION: In our small
      series of patients with extreme TSH elevations, none had a serum sodium level
      below normal (<135 mmol/L), even in the presence of a reduced GFR. Hyponatremia
      can be a common occurrence in hospitalized and/or chronically ill patients;
      however, in an otherwise relatively healthy ambulatory patient, hypothyroidism,
      even when severely undertreated, may be a less clinically relevant cause of
      hyponatremia.

PMID- 22982799
TI  - Differential diagnosis of adrenocorticotropic hormone-independent Cushing
      syndrome: role of adrenal venous sampling.
AB  - OBJECTIVE: To outline the potential role for adrenal venous sampling in the
      diagnosis and management of adrenocorticotropic hormone (ACTH)-independent
      Cushing syndrome (CS). METHODS: We present a case description and discuss the
      management of a 59-year-old woman with an 8-year history of weight gain,
      centripetal obesity, a round plethoric face, skin thinning, easy bruising,
      hirsutism, and progressive muscle weakness. RESULTS: The patient reported a prior
      personal history of asthma, type 2 diabetes mellitus, hypertension, dyslipidemia,
      and bilateral leg ulcers, but she denied having any personal or family history of
      endocrinopathy and was not taking any corticosteroid medication. Elevated
      midnight serum cortisol, failure to suppress cortisol levels with a low-dose
      dexamethasone suppression test, and undetectable plasma ACTH all indicated ACTH
      independent CS. Additional investigations including dynamic tests and adrenal
      imaging were supported by adrenal venous sampling in order to make a diagnosis
      and formulate a management plan. She was ultimately noted to have bilateral
      functioning adrenal nodules (adenoma and adenolipoma) and underwent successful
      bilateral laparoscopic adrenalectomy, with postoperative glucocorticoid and
      mineralocorticoid replacement. CONCLUSION: Adrenal venous sampling may be an
      important step in the differential diagnosis of CS and localization of the source
      of cortisol excess. It may distinguish pheochromocytoma or benign nonfunctioning
      adrenal nodules from cortisol-secreting adenomas and may avoid unnecessary
      bilateral adrenalectomy. It can also ensure that the correct operation is
      completed, if required, and thus avoid the increased morbidity and mortality
      associated with repeated surgical interventions.

PMID- 22982800
TI  - Visual vignette.

PMID- 22982801
TI  - Association of Clinical Researchers and Educators a statement on relationships
      between physicians and industry.
AB  - Collaborations between physicians, particularly those in academic medicine, and
      industries that develop pharmaceutical products, medical devices, and diagnostic
      tests have led to substantial advances in patient care. At the same time, there
      is a strong awareness that these relationships, however beneficial they may be,
      should conform to established principles of ethical professional practice.
      Through a writing committee drawn from diverse disciplines across several
      institutions, the Association of Clinical Researchers and Educators (ACRE) has
      written a code of conduct to provide guidance to physicians in observing these
      principles. Our recommendations are not intended to be prescriptive or
      inflexible, but rather to be of assistance to physicians in making their own
      personal decisions on whether, or how, to be involved in research, education, or
      other collaborations with industry.

PMID- 22982802
TI  - Primary hyperparathyroidism.
AB  - OBJECTIVE: To review primary hyperparathyroidism and the key issues that are
      relevant to the practicing endocrinologist. METHODS: The latest information on
      the presentation, diagnosis, and traditional and nontraditional aspects of
      primary hyperparathyroidism is reviewed. RESULTS: The diagnosis of primary
      hyperparathyroidism is straightforward when the traditional hypercalcemic patient
      is documented to have an elevated parathyroid hormone (PTH) level. Commonly,
      patients are identified who have normal serum calcium levels but elevated PTH
      levels in whom no secondary causes for hyperparathyroidism can be confirmed.
      Traditional target organs of primary hyperparathyroidism-the skeleton and the
      kidneys-continue to be a focus in the patient evaluation. Bone mineral density
      shows a typical pattern of involvement with the distal one-third radius being
      selectively reduced compared with the lumbar spine in which bone mineral density
      is generally well maintained. Neurocognitive and cardiovascular aspects of
      primary hyperparathyroidism, while a focus of recent interest, have not been
      shown to definitively aid in the decision for or against surgery. The
      recommendation for surgery in primary hyperparathyroidism is based on guidelines
      that focus on the serum calcium level, renal function, bone mineral density, and
      age. In patients who do not meet guidelines, a nonsurgical management approach
      has merit. CONCLUSIONS: Primary hyperparathyroidism is continuing to show changes
      in its clinical profile, with normocalcemic primary hyperparathyroidism being a
      topic of great interest. Skeletal and renal features of primary
      hyperparathyroidism drive, in most cases, the decision to recommend surgery. In
      patients who do not meet any criteria for surgery, a conservative approach with
      appropriate monitoring is acceptable.

PMID- 22982803
TI  - Diagnostic use of molecular markers in the evaluation of thyroid nodules.
AB  - OBJECTIVE: To describe the molecular markers thus far evaluated for use in the
      care of patients with clinically relevant thyroid nodules. METHODS: We review the
      currently available molecular tests that have been applied to patients with
      thyroid nodules. RESULTS: In the United States, approximately 450 000 diagnostic
      fine-needle aspirates will be performed on patients with thyroid nodules this
      year in an effort to identify thyroid cancer. Unfortunately, this test is
      imprecise and, at times, inaccurate. Because of this, novel diagnostic testing
      modalities have been pursued, the most promising of which involve molecular
      analysis of thyroid tissue. Immunohistochemical staining, analysis for mutations
      and gene rearrangements, and microarray analysis have all been investigated with
      regard to their performance characteristics in targeted patient populations.
      CONCLUSIONS: Molecular tests to evaluate thyroid nodules demonstrate variable
      performance characteristics. Further evaluation of available and emerging
      molecular tests will necessarily rely on prospective real-world test validation
      in the clinical setting.

PMID- 22982804
TI  - Pomegranate pericarp extract enhances the antibacterial activity of ciprofloxacin
      against extended-spectrum beta-lactamase (ESBL) and metallo-beta-lactamase (MBL)
      producing Gram-negative bacilli.
AB  - A methanolic extract of Punica granatum (pomegranate) fruit pericarp (PGME) was
      tested in combination with ciprofloxacin against extended-spectrum beta-lactamase
      (ESBL) producing Escherichia coli, Klebsiella pneumoniae, and metallo-beta
      lactamase (MBL) producing Pseudomonas aeruginosa, which were screened for their
      resistance profile against fluoroquinolone antibiotics. The minimum inhibitory
      concentrations (MIC) of ciprofloxacin and PGME, alone, were determined, and
      synergy of ciprofloxacin-PGME combinations evaluated by checkerboard assay and
      fractional inhibitory concentration (FIC). Nineteen out of forty-nine strains
      exhibited synergy with ciprofloxacin (FIC of 0.125-0.5 for ciprofloxacin) further
      verified by agar-well assay. This could be due to the bacterial efflux pump
      inhibitor (EPI) activity of the polyphenolic constituents of PGME. However, the
      isolates exhibiting a high level of ciprofloxacin resistance did not respond to
      ciprofloxacin-PGME combinations, which could be due to target site modification
      not influenced further by EPI activity of PGME. Again, some strains were
      sensitive or weakly resistant to ciprofloxacin, which exhibited 'indifference' to
      the combination, probably due to a lack of over-expressed efflux mechanism. Thus,
      a synergy of a ciprofloxacin-PGME combination was demonstrated for the first time
      against ESBL- and MBL-producing Gram-negative bacilli, and the efficacy of an
      existing drug improved with the help of an inexpensive alternative therapy.

PMID- 22982805
TI  - Saucerneol D inhibits eicosanoid generation and degranulation through suppression
      of Syk kinase in mast cells.
AB  - Previously we reported that saucerneol D (SD), a naturally occurring sesquilignan
      isolated from Saururus chinensis (S. chinensis) suppressed lipopolysaccharide
      (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. The aim of this
      study was to elucidate whether SD modulates the generation of other inflammatory
      mediators in activated mast cells. We investigated the effects of SD on
      cyclooxygenase-2 (COX-2)-dependent prostaglandin D(2) (PGD(2)) and 5-lipoxygenase
      (5-LO)-dependent leukotriene C(4) (LTC(4)) generations as well as degranulation
      in cytokine-stimulated mouse bone marrow-derived mast cells (BMMCs). Biochemical
      analyses of the cytokine-mediated signaling pathways showed that SD suppressed
      the phosphorylation of Syk kinase and multiple downstream signaling processes
      including phospholipase Cgamma1 (PLCgamma1)-mediated intracellular Ca(2+) influx
      and activation of mitogen-activated protein kinases (MAPKs; including
      extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH(2)-terminal kinase
      (JNK) and p38) and the nuclear factor-kappaB (NF-kappaB) pathway. Taken together,
      the present study suggests that SD suppresses eicosanoid generation and
      degranulation through Syk-dependent pathway in BMMCs.

PMID- 22982806
TI  - The physics of wind-blown sand and dust.
AB  - The transport of sand and dust by wind is a potent erosional force, creates sand
      dunes and ripples, and loads the atmosphere with suspended dust aerosols. This
      paper presents an extensive review of the physics of wind-blown sand and dust on
      Earth and Mars. Specifically, we review the physics of aeolian saltation, the
      formation and development of sand dunes and ripples, the physics of dust aerosol
      emission, the weather phenomena that trigger dust storms, and the lifting of dust
      by dust devils and other small-scale vortices. We also discuss the physics of
      wind-blown sand and dune formation on Venus and Titan.

PMID- 22982807
TI  - The role of liposome size on the type of immune response induced in BALB/c mice
      against leishmaniasis: rgp63 as a model antigen.
AB  - To develop an efficient liposomal vaccine delivery system, the size of liposomes
      is critical to their adjuvant activities. In the present study, liposomes with
      different sizes (100, 400, 1000 nm) containing recombinant major surface
      glycoprotein of Leishmania (rgp63) were prepared, characterized, and inoculated
      subcutaneously into BALB/c mice to evaluate the rate of protection and the type
      of immune response generated against leishmaniasis. The lowest footpad lesion
      size and splenic parasite burden were seen in the mice immunized with large size
      (>=400 nm) liposomes after challenge with Leishmania major. The production of IFN
      gamma was only elevated in the spleen cells of mice immunized with large size
      (>=400 nm) liposomes. The highest IgG2a/IgG1 ratio was also seen in the sera of
      the mice immunized with large size (>=400 nm) liposomes before and 14 weeks after
      challenge. The results showed that immunization with small size (100 nm)
      liposomes induces a Th2 response, whereas immunization with large size (>=400 nm)
      liposomes induces a Th1 type of immune response. There was no significant
      difference in the type of induced immune response between the mice immunized with
      liposomes of 400 nm and those immunized with liposomes of 1000 nm or unextruded.
      The results of the current study demonstrated that the size of liposomes plays a
      significant role in the type of generated immune response.

PMID- 22982808
TI  - Functional characterization of TcCYC2 cyclin from Trypanosoma cruzi.
AB  - In eukaryotes, an oscillating network of protein kinase activities drives the
      order and timing of the cell cycle progression. Complexes formed by cyclins
      associated to cyclin-dependent kinases (CDKs) are the central components of this
      network. Cyclins act as the activating subunits and their abundance is regulated
      by different mechanisms in order to promote or prevent kinase activity. Protein
      synthesis, proteasomal degradation and/or differential subcellular
      compartmentalization modulate cyclin expression levels along the cell cycle. We
      describe in this work the characterization of Trypanosoma cruzi Cyclin 2
      (TcCYC2), which contributes to a better understanding of the cell cycle
      regulation in this protozoan parasite. We found TcCYC2 exhibited cyclin function
      in a yeast complementation assay and over-expression of hemagglutinin tagged
      TcCYC2-HA rendered shorter duplication times and smaller cell sizes in the
      epimastigote form of the parasite. Analysis of synchronized cultures showed that
      over-expression of TcCYC2-HA altered the timing epimastigotes pass through G2/M
      boundary or cytokinesis. Taken together, our results showed that TcCYC2 is a
      functional cyclin whose over-expression modifies the dynamics of the cell cycle
      as well as the morphology of epimastigote forms of T. cruzi, suggesting it plays
      an important role in the cell cycle regulation machinery.

PMID- 22982809
TI  - Antioxidant activities of lignin extracted from sugarcane bagasse via different
      chemical procedures.
AB  - Lignin was extracted from sugarcane bagasse via different chemical procedures
      with ethanol and alkaline solutions. The products (EL, AL) were characterized by
      UV, FT-IR, (13)C NMR, TGA, GPC and potentiometric titration. The results
      indicated AL had more phenolic hydroxyl (PhOH) and methoxyl groups (OCH(3)), and
      larger molecular mass and better thermal stability than EL. The lignins were
      further evaluated as potential antioxidants. The results demonstrated the radical
      scavenging activity (RSA) of AL was 79.0%, 91.3% higher than EL at the
      concentration of 300 mg L(-1). The stronger antioxidant activity of AL was due to
      its higher quantities of PhOH and OCH(3) groups.

PMID- 22982810
TI  - Antioxidant and hepatoprotective potential of endo-polysaccharides from Hericium
      erinaceus grown on tofu whey.
AB  - Three fractions of the endo-polysaccharides from the mycelium of Hericium
      erinaceus (HEP) grown on tofu whey were obtained by the fractional precipitation
      with gradient concentrations of ethanol (HEP40, HEP60 and HEP80). The chemical
      and physical characteristics of the three crude polysaccharides were investigated
      by the combination of chemical and instrumental analysis methods. The studies to
      evaluate the antioxidant potential and the hepatoprotective effects of the three
      polysaccharides showed that they had different activities in different evaluation
      system. HEP80 showed strong activity on antioxidant in vitro and potent
      hepatoprotective effect in vivo and the hepatoprotective effect may be due to its
      potent antioxidant capacity. The HEP could be exploited as antioxidant product
      and a supplement in the prevention of hepatic diseases. The study also opens an
      avenue for the efficient utilization of tofu whey, which is usually discarded in
      environment, causing concerns.

PMID- 22982811
TI  - Synthesis and characterization of novel nano-chitosan Schiff base and use of lead
      (II) sensor.
AB  - A new kind of nano-chitosan Schiff base ligand (CHNS) with particle size of 34 nm
      was formed by the reaction between the 2-amino groups of glucosamine residue of
      nano-chitosan and a 2,5-dihydroxybenzaldehyde. The chemical structures of the
      nano-chitosan and nano-chitosan Schiff base were characterized by FT-IR spectra,
      particle sizer, zeta potential, and elemental analysis. A new, simple and
      effective chemically modified carbon paste electrode with CHNS was prepared and
      used as a lead (II) sensor. The prepared electrode was characterized using
      scanning electronic microscopy (SEM-EDX) and cyclic voltammetry (CV). The
      modified electrode showed only one oxidation peak in the anodic scan at -0.34 V
      (vs. Ag/AgCl) for the oxidation of lead (II). The dedection limit (LOD) was
      calculated as 1.36*10(-7) for a 10-min preconcentration time at pH 6.0.

PMID- 22982812
TI  - Characterization and in vitro antitumor activity of polysaccharides from the
      mycelium of Sarcodon aspratus.
AB  - Polysaccharides extracted from mushrooms have shown a variety of medical
      activities, such as antitumor, immunostimulatory and hypoglycemic activity. In
      this study, characteristics and the antitumor activities of Sarcodon aspratus
      polysaccharides were investigated for the possibility of application of S.
      aspratus in health care and medicine. Two polysaccharide fractions (PSAN and
      PSAA) were extracted and isolated from the mycelium of S. aspratus. The average
      molecular weight of PSAN and PSAA were approximately 5.6*10(4) Da and 3.83*10(5)
      Da, respectively. PSAN was composed of L-rhamnose, D-xylose and D-mannose, with
      molar ratios of 1:10:21; PSAA consisted of L-rhamnose, D-xylose, D-mannose, D
      glucose and D-galactose, with molar ratios of 1:39:76:10:21. Both PSAN and PSAA
      presented high antitumor activity against Hela cells in vitro. At a concentration
      of 400 mg/L and an exposure time of 24h, the inhibition rates for PSAN and PSAA
      were 65% and 80%, respectively. PSAN and PSAA exhibited significantly lower
      cytotoxicity against human normal liver cell line L-02 than Hela tumor cells in
      comparison with 5-Fu. Polysaccharide extracted from an edible mushroom S.
      aspratus may be a potential candidate for developing a novel low toxicity
      antitumor agent.

PMID- 22982813
TI  - Room temperature tandem hydroamination and hydrosilation/protodesilation
      catalysis by a tricarbonylchromium-bound iridacycle.
AB  - A chromiumtricarbonyl-bound iridacycle displays novel catalytic virtues for the
      conversion of terminal aromatic alkynes into racemic N-phenyl, 1-arylethylamines
      by tandem hydro-amination and hydrosilation/protodesilation reactions under mild
      "one pot" conditions.

PMID- 22982814
TI  - Novel insights into cyclooxygenases, linoleate diol synthases, and lipoxygenases
      from deuterium kinetic isotope effects and oxidation of substrate analogs.
AB  - Cyclooxygenases (COX) and 8R-dioxygenase (8R-DOX) activities of linoleate diol
      synthases (LDS) are homologous heme-dependent enzymes that oxygenate fatty acids
      by a tyrosyl radical-mediated hydrogen abstraction and antarafacial insertion of
      O(2). Soybean lipoxygenase-1 (sLOX-1) contains non-heme iron and oxidizes 18:2n-6
      with a large deuterium kinetic isotope effect (D-KIE). The aim of the present
      work was to obtain further mechanistic insight into the action of these enzymes
      by using a series of n-6 and n-9 fatty acids and by analysis of D-KIE. COX-1
      oxidized C(20) and C(18) fatty acids in the following order of rates: 20:2n
      6>20:1n-6>20:3n-9>20:1n-9 and 18:3n-3>=18:2n-6>18:1n-6. 18:2n-6 and its
      geometrical isomer (9E,12Z)18:2 were both mainly oxygenated at C-9 by COX-1, but
      the 9Z,12E isomer was mostly oxygenated at C-13. A cis-configured double bond in
      the n-6 position therefore seems important for substrate positioning. 8R-DOX
      oxidized (9Z,12E)18:2 at C-8 in analogy with 18:2n-6, but the 9E,12Z isomer was
      mainly subject to hydrogen abstraction at C-11 and oxygen insertion at C-9 by 8R
      DOX of 5,8-LDS. sLOX-1 and 13R-MnLOX oxidized [11S-(2)H]18:2n-6 with similar D
      KIE (~53), which implies that the catalytic metals did not alter the D-KIE.
      Oxygenation of 18:2n-6 by COX-1 and COX-2 took place with a D-KIE of 3-5 as
      probed by incubations of [11,11-(2)H(2)]- and [11S-(2)H]18:2n-6. In contrast, the
      more energetically demanding hydrogen abstractions of the allylic carbons of
      20:1n-6 by COX-1 and 18:1n-9 by 8R-DOX were both accompanied by large D-KIE
      (>20).

PMID- 22982815
TI  - Integrating the puzzle pieces: the current atomistic picture of phospholipid-G
      protein coupled receptor interactions.
AB  - A compelling question of how phospholipids interact with their target receptors
      has been of interest since the first receptor-mediated effects were reported. The
      recent report of a crystal structure for the S1P(1) receptor in complex with an
      antagonist phospholipid provides interesting perspective on the insights that had
      previously been gained through structure-activity studies of the phospholipids,
      as well as modeling and mutagenesis studies of the receptors. This review
      integrates these varied lines of investigation in the context of their various
      contributions to our current understanding of phospholipid-receptor interactions.
      This article is part of a Special Issue entitled Advances in Lysophospholipid
      Research.

PMID- 22982816
TI  - The mental health of internally displaced persons: an epidemiological study of
      adults in two settlements in Central Sudan.
AB  - AIMS: There is a scarcity of data on mental health problems among Sudanese
      internally displaced persons (IDPs). This study aims to assess the prevalence of
      mental disorders of IDPs in Sudan, and to determine and compare the association
      between mental disorders and socio-demographic variables between the rural and
      urban long-term IDP populations. METHODS: This cross-sectional study was
      implemented in two IDP areas in Central Sudan. Data were collected during face-to
      face interviews using structured questionnaires to assess socio-demographic
      factors and the Mini International Neuropsychiatric Interview (MINI) to determine
      psychiatric diagnoses. A total of 1,876 adults were enrolled from both study
      areas. RESULTS: The overall prevalence of having any mental health disorder in
      the IDP population was 52.9%. The most common disorders were major depressive
      disorder (24.3%), generalized anxiety disorder (23.6%), social phobia (14.2%) and
      post-traumatic stress disorder (12.3%). Years of displacement and education were
      associated with different mental disorders between the two areas, and there were
      no gender differences in prevalence of mental disorders in either area.
      CONCLUSION: This study shows high prevalence rates of mental disorders in both
      urban and rural IDP populations in Sudan, indicating a need to explore the
      circumstances for these high rates and to develop appropriate responses.

PMID- 22982817
TI  - Forces driving change in medical diagnostics.
AB  - This article reviews the external forces that affect and shape the future of
      medical diagnostics. A PESTELI model is retrospectively used to highlight the
      factors that drive change at an operational and management level. The author
      describes the future picture of clinical laboratory diagnostics and proposes ways
      to overcome current and pending challenges on clinical laboratories and
      university curriculum. An international committee with broad expertise in
      clinical laboratory diagnostics is proposed to examine these changes and provide
      guidance.

PMID- 22982818
TI  - Inflexinol reduces severity of acute pancreatitis by inhibiting nuclear factor
      kappaB activation in cerulein-induced pancreatitis.
AB  - OBJECTIVES: To examine the effect of inflexinol on the development of acute
      pancreatitis (AP) and to investigate the mechanisms responsible for the
      protective effect against AP. METHODS: Acute pancreatitis was induced in mice by
      intraperitoneal injection of cerulein. Inflexinol was administered
      intraperitoneally 4 times every 6 hours from 1 hour before the first cerulein
      injection. Serum amylase activity and histology of the pancreas were measured.
      Determination of pancreatic nuclear factor-kappaB (NF-kappaB) p65 expression was
      conducted by Western blotting and immunohistochemistry to investigate the
      mechanisms responsible for the inflexinol effects. RESULTS: Serum amylase
      activity in the cerulein group was significantly higher than that in the control
      group (P < 0.05). Pancreatic histology revealed marked inflammatory changes in
      the cerulein group such as interstitial edema, vacuolization, necrosis, and
      infiltration of inflammatory cells; and Western blotting and immunohistochemistry
      showed marked NF-kappaB p65 expression. Treatment with inflexinol significantly
      attenuated the inflammatory changes in pancreatic histology at 24, 48, and 72
      hours (P < 0.05). Pancreatic NF-kappaB p65 expression decreased significantly
      after inflexinol treatment (P < 0.05). CONCLUSION: Inflexinol reduced the
      severity of cerulein-induced AP by inhibiting NF-kappaB activation.

PMID- 22982819
TI  - Ion transport in human pancreatic duct epithelium, Capan-1 cells, is regulated by
      secretin, VIP, acetylcholine, and purinergic receptors.
AB  - OBJECTIVES: The objective of the study was to establish a solid model of
      polarized epithelium for human pancreatic ducts, where electrical parameters
      could be measured as indicators of ion transport. Further, we aimed to determine
      functional expression of several receptors, in particular, purinergic receptors,
      and determine their effects on ion transport. METHODS: Human adenocarcinoma cell
      line Capan-1 cells were grown on permeable supports and set in Ussing chambers
      for electrophysiological recordings. Transepithelial voltage (Vte), resistance,
      and short-circuit currents (Isc) were measured in response to agonists. RESULTS:
      Secretin, vasoactive intestinal peptide (VIP), acetylcholine, forskolin,
      ionomycin, adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP), 3'-O
      (4-benzoyl)benzoyl ATP, and adenosine induced lumen negative Vte and Isc. These
      changes were consistent with anion secretion, as verified in forskolin-stimulated
      preparations. Extracellular nucleotides, ATP, and UTP, applied from luminal and
      basolateral sides, caused largest responses: Vte increased up to -5 mV, Isc
      increased to 20 to 30 MUA/cm, and resistance decreased by up to 200 Omega.cm.
      CONCLUSIONS: Transepithelial transport in human pancreatic duct epithelium, Capan
      1 cells, is regulated by secretin, VIP, acetylcholine, adenosine, and purinergic
      P2 receptors; and this human model has a good potential for studies of physiology
      and pathophysiology of pancreatic duct ion transport.

PMID- 22982820
TI  - Early hemodynamic variables and outcome in severe acute pancreatitis: a
      retrospective single-center cohort study.
AB  - OBJECTIVES: The aim of this study was to assess the association of hemodynamic
      factors with 90-day mortality in critically ill patients with severe acute
      pancreatitis (SAP). METHODS: One hundred fifty-nine consecutive patients with SAP
      admitted to the intensive care units between January 2005 and December 2008 were
      included in study. We assessed the association of hemodynamic variables during
      the first 24 hours in the intensive care unit with 90-day mortality using
      multivariate analysis for all patients with SAP and for a subgroup with
      circulatory shock. RESULTS: Advanced age (odds ratio [OR], 1.09; 95% confidence
      interval, 1.04-1.15 per year), higher serum creatinine (OR, 1.01; 95% confidence
      interval, 1.00-1.02 per unit), and lower mean arterial pressure (OR, 0.92; 95%
      confidence interval, 0.86-0.99 per mm Hg) were independently associated with 90
      day mortality. In the subgroup of SAP with shock, higher Acute Physiology and
      Chronic Health Evaluation II score (OR, 1.15; 95% confidence interval, 1.00-1.32
      per point), higher central venous pressure (OR, 1.25; 95% confidence interval,
      1.03-1.52 per mm Hg), and lower cardiac index (OR, 0.33; 95% confidence interval,
      0.11-0.98 per L/min per m2) were independent risk factors for 90-day mortality.
      CONCLUSIONS: Advanced age, higher serum creatinine, and lower mean arterial
      pressure are associated with 90-day mortality in patients with SAP. In the
      subgroup of patients with SAP and shock, higher Acute Physiology and Chronic
      Health Evaluation II score, higher central venous pressure, and lower cardiac
      index predicted 90-day mortality.

PMID- 22982821
TI  - Visual detection of filaria-specific IgG4 in urine using red-colored high density
      latex beads.
AB  - The use of urine for the immunodiagnosis of lymphatic filariasis has a definite
      advantage: the sample collection is not invasive and thus well accepted by
      people. Urine-based ELISA to detect filaria-specific IgG4 has been used
      successfully. However, ELISA requires equipment such as a microplate reader,
      which is often not available in most endemic areas. We have developed a new
      visual immunodiagnosis that detects urinary IgG4 using red-colored latex beads
      (bead test). The sensitivity was 87.2% when ICT antigen test positive people were
      regarded as the standard (136/156), and the specificity was 97.2% with the non
      endemic people in Japan and Bangladesh, and the urine ELISA negatives in Sri
      Lanka (1264/1300). In a prevalence study, the bead test could detect filarial
      infection more effectively than ICT test among young children in Sri Lanka,
      indicating the usefulness of the visual test in epidemiological studies.

PMID- 22982822
TI  - Symptomatic pulmonary embolism among stroke patients in Taiwan: a retrospective
      cohort study.
AB  - BACKGROUND: Stroke patients are at particular risk for developing pulmonary
      embolism (PE), which is a cardiovascular emergency associated with a high
      mortality rate. Little information is available on symptomatic PE in Asian stroke
      patients. OBJECTIVE: To determine the frequency of symptomatic PE in ischemic and
      hemorrhagic stroke patients; to identify common characteristics and risk factors
      of symptomatic PE in Taiwanese stroke patients; and to compare the difference
      between fatal PE and nonfatal PE among these stroke patients. METHODS: This is a
      retrospective cohort study of stroke patients admitted between January 2002 and
      December 2009 to a tertiary referral center in Northern Taiwan. We used the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes to identify eligible patients. We determined annual frequency and risk
      factors of symptomatic PE. We also compared the difference between ischemic
      stroke patients with fatal and nonfatal PE. RESULTS: Among the admitted stroke
      patients, 21,129 (78.87%) had ischemic strokes and 5,662 (21.13 %) had
      hemorrhagic strokes. There were 14 (0.066%) ischemic and 1 hemorrhagic stroke
      (0.018%) patients included in this study. Of the recruited stroke patients,
      64.29% had past heart disease history, especially atrial fibrillation (42.86%).
      Patients with fatal PE showed a significantly lower poststroke Glasgow Coma Scale
      (GCS) motor component than patients with nonfatal PE. CONCLUSIONS: Symptomatic PE
      is not common in stroke patients in Taiwan. Clinicians need to keep this fatal
      disease in mind, especially for persons with heart disease like atrial
      fibrillation. Stroke patients with impaired poststroke GCS motor components
      seemed to have a greater mortality risk if they have symptomatic PE.

PMID- 22982823
TI  - Physical factors associated with fatigue after stroke: an exploratory study.
AB  - OBJECTIVE: To look for a relationship between physical fatigue and physical
      parameters in patients at least 3 months post stroke. METHODS: We conducted a
      prospective cross-sectional study of 32 poststroke patients (average duration of
      stroke 40 months) who were recruited among in- and outpatients followed by the
      Department of Physical and Rehabilitation Medicine of a university hospital.
      Fatigue was defined as a Fatigue Severity Scale (FSS) score of 4 or more. The
      parameters studied were age, sex, time since stroke, Demeurisse Motor Index,
      Barthel Index score, new Functional Ambulation Category, Berg Balance Scale, 10
      meter walk test, 6-minute walk test, Dijon Physical Activity Score, Montgomery
      and Asberg Depression Rating Scale, Epworth Sleepiness Scale, presence of pain,
      and length and area of the center of pressure displacement obtained
      posturographically. RESULTS: Two-thirds of patients (65.6%) were fatigued. The
      mean FSS score was 4.3 +/- 1.8. Fatigue was not associated with the physical
      parameters studied; notably, there was no correlation with motor impairment,
      autonomy and walking capacity, or balance and physical activity. However, after
      multivariate analysis, we found an association between physical fatigue and time
      since the occurrence of stroke (P = .05). CONCLUSIONS: Our study revealed a
      relationship between pain and physical fatigue, as reported by 2 other studies.
      Poststroke fatigue management should include appropriate pain management. Further
      studies are necessary to determine the causes of physical fatigue after stroke.

PMID- 22982824
TI  - Effect of intensive rehabilitation on physical function and arterial function in
      community-dwelling chronic stroke survivors.
AB  - BACKGROUND: Atherothrombosis due to arteriosclerosis is a risk factor for
      recurrence of stroke. Although exercise therapy is essential to prevent
      progression of arteriosclerosis and to improve endothelial function, little is
      known about the effect of rehabilitation in chronic stroke survivors. OBJECTIVE:
      The purpose of this study was to investigate the effect of intensive
      rehabilitation on physical and arterial function among community-dwelling stroke
      survivors. METHODS: Forty-four community-dwelling stroke survivors participated
      in the study. The experimental group (n = 22) received primarily intensive
      strengthening exercise and the control group (n = 22) received standard physical
      therapy consisting mainly of stretching and gait training. Both groups underwent
      the rehabilitation program for 12 weeks. Physical function was evaluated using 10
      m gait velocity, the 30-s chair stand test, Timed Up and Go test, and grip
      strength. Arterial function of the affected and unaffected sides was evaluated
      using the cardio-ankle vascular index (CAVI) as an index of arterial stiffness
      and the ankle-brachial pressure index (ABI) as an index of arterial occlusion.
      RESULTS: After the 12-week rehabilitation period, improvement in physical
      function did not differ between the 2 groups; whereas with regard to arterial
      function, a significant improvement in the CAVI for the affected side was
      observed in the experimental group (P < .001). Also, the ABI for the unaffected
      side in the experimental group was significantly improved after intervention (P <
      .001). No significant differences were found for the unaffected-side CAVI and
      affected-side ABI between the 2 groups. CONCLUSIONS: These findings suggested
      that intensive rehabilitation for stroke patients during the chronic stage
      preserved physical function and improved arterial function.

PMID- 22982825
TI  - Complementary and alternative medicine treatments among stroke patients in India.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is commonly used by
      persons with stroke throughout the world, particularly in Asia. OBJECTIVE: The
      objectives of this study were to determine the frequency of CAM use and the
      factors that predict the use of CAM in stroke patients. METHODS: This study was
      carried out in the stroke units of Christian Medical College, Ludhiana, and Sree
      Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram,
      India, from June 2010 to December 2010. Participants were interviewed using a
      structured questionnaire (>= 6 months post stroke). Outcomes were assessed using
      a modified Rankin Scale (mRS). RESULTS: Three hundred fourteen stroke patients
      were interviewed; mean age was 57.4 +/- 12.9 years, and 230 (73.2%) patients were
      men. Of 314 patients, 114 (36.3%) had used the following CAM treatments:
      ayurvedic massage, 67 (59.3%); intravenous fluids, 22 (19.5%); herbal medicines,
      17 (15%); homeopathy, 15 (13.3%); witchcraft, 3 (2.7%); acupuncture, 3 (2.7%);
      opium intake, 10 (8.8%); and other nonconventional treatments, 10 (8.8%).
      Patients with severe stroke (P < .0001), limb weakness (P < .0001), dysphagia (P
      = .02), dyslipidemia (P = .007), hypertension (P = .03), or hemorrhagic stroke
      (P<.0001) and patients with poor outcome (mRS >2;P < .0001) often used CAM
      treatments. CONCLUSION: More than one-third of the patients in this study opted
      for CAM. Presence of limb weakness, dysphagia, dyslipidemia, hypertension,
      hemorrhagic stroke, severe stroke, and poor outcome predicted the use of CAM.

PMID- 22982826
TI  - Rehabilitation experts' experience of community rehabilitation services for
      stroke survivors in Iran.
AB  - PURPOSE: Successful stroke rehabilitation is a complex process involving teamwork
      by members of several professions. The aims of this study were to explore the
      experiences of Iranian rehabilitation experts concerning community rehabilitation
      services for stroke survivors and obtain their opinions on how to further develop
      and improve these services. METHOD: A qualitative research method with grounded
      theory was used, including purposive and theoretical sampling. A constant
      comparative analysis was conducted. Data were gathered from 2 focus group
      discussions including 10 Iranian rehabilitation experts and 4 in-depth individual
      interviews. RESULTS: Nonintegrated rehabilitation services emerged as the core
      concept of the study. The explored concepts were identified as deficiently
      allocated budget, inadequate public insurance, lack of availability of
      rehabilitative care, negative public opinion, lack of consistency in care, and
      split services and professional separation. Areas identified for potential
      improvement included need to change policymakers' attitudes, need to refine
      rehabilitation in the health care system, need to establish a registration
      system, need to provide information and skills, and need to see the family as a
      whole. CONCLUSION: Experts should participate in educational rehabilitation
      programs to become more aware of current rehabilitation services within the
      community. Stroke survivors and their families should also participate in the
      rehabilitation programs as this would allow them to gain knowledge and skills for
      dealing with stroke management. This can help reduce problems, change public
      opinion, and eliminate mistrust between health care providers and families.

PMID- 22982827
TI  - Physiotherapy practice in stroke rehabilitation: a cross-sectional survey of
      physiotherapists in the state of Kerala, India.
AB  - BACKGROUND: Physiotherapy, a major component of rehabilitation for stroke
      patients, has been shown to have a positive effect on outcome. However, there is
      debate over efficacy of different interventions related to stroke rehabilitation.
      PURPOSE: The purpose of this study was to compare knowledge and attitudes of
      physiotherapists working with stroke patients in Kerala, India, with emphasis on
      demographics, approach to treatment, and beliefs about stroke rehabilitation.
      METHODS: Two hundred one physiotherapists in Kerala were surveyed using
      questionnaires, which were sent by post. Questionnaires consisted of items
      related to stroke rehabilitation such as approaches to physiotherapy, use of
      walking aids, and discharge issues. Data analysis was done using percentage-wise
      comparisons. RESULTS: Examination of results showed variation in the beliefs held
      by physiotherapists about treatment of stroke patients. Of the 201 respondents,
      153 (76.1%) used a conventional treatment approach. There was a strong disparity
      among physiotherapists regarding use of walking aids by stroke patients: 119
      (59.2%) agreed that tripods or quadripods should be given to patients, but 55
      (27.4%) disagreed and 27 (13.4%) were unsure. In response to questions about
      discharge issues, 30 (14.9%) of the 118 respondents agreed that they were
      actively involved in discharge planning for stroke patients, and 158 (78.6%)
      agreed that skill of the physiotherapist influences outcomes. CONCLUSION: A great
      deal of variation among physiotherapists in treatment approaches and beliefs was
      revealed in this study, which indicates the need for development and
      implementation of a standardized protocol for stroke rehabilitation in Kerala.

PMID- 22982828
TI  - Functional self-efficacy and its determinants in Nigerian stroke survivors.
AB  - BACKGROUND: Self-efficacy enhances functional recovery and the overall outcome of
      rehabilitation after stroke. OBJECTIVE: The objective of this study was to
      identify factors influencing functional self-efficacy in stroke survivors in a
      regional medical center in northeastern Nigeria. METHODS: A cross-sectional study
      of 50 stroke survivors attending the physiotherapy clinic of the University of
      Maiduguri, Nigeria, was conducted. Information on the sociodemographic and
      clinical characteristics of participants was obtained. Functional ability and
      self-efficacy were assessed using the modified Rankin Scale and Functional
      Ability Confidence Scale, respectively. RESULTS: The mean functional self
      efficacy score of stroke survivors in this study was below average. Marital
      status and functional ability influenced functional self-efficacy. Very high
      functional efficacy scores were observed among those who reported no functional
      disability. CONCLUSION: The study shows a reciprocal relationship between
      functional ability and functional self-efficacy. It is expected that enhancement
      of functional ability in stroke rehabilitation will help boost functional self
      efficacy of stroke survivors and vice versa.

PMID- 22982829
TI  - Assessing the suitability of written stroke materials: an evaluation of the
      interrater reliability of the suitability assessment of materials (SAM)
      checklist.
AB  - PURPOSE: Written materials are frequently used to provide education to stroke
      patients and their carers. However, poor quality materials are a barrier to
      effective information provision. A quick and reliable method of evaluating
      material quality is needed. This study evaluated the interrater reliability of
      the Suitability Assessment of Materials (SAM) checklist in a sample of written
      stroke education materials. METHODS: Two independent raters evaluated the
      materials (n = 25) using the SAM, and ratings were analyzed to reveal total
      percentage agreements and weighted kappa values for individual items and overall
      SAM rating. RESULTS: The majority of the individual SAM items had high interrater
      reliability, with 17 of the 22 items achieving substantial, almost perfect, or
      perfect weighted kappa value scores. The overall SAM rating achieved a weighted
      kappa value of 0.60, with a percentage total agreement of 96%. CONCLUSION: Health
      care professionals should evaluate the content and design characteristics of
      written education materials before using them with patients. A tool such as the
      SAM checklist can be used; however, raters should exercise caution when
      interpreting results from items with more subjective scoring criteria.
      Refinements to the scoring criteria for these items are recommended. The value of
      the SAM is that it can be used to identify specific elements that should be
      modified before education materials are provided to patients.

PMID- 22982831
TI  - Bone mineral density in patients with stroke: relationship with motor impairment
      and functional mobility.
AB  - PURPOSE: Patients with stroke have a 2- to 4-fold increased risk of hip fracture
      compared to the general population, because of decreased bone mineral density
      (BMD) on the paretic side and the high incidence of accidental falls. However,
      the relationship between BMD and stroke-related motor impairment and functional
      mobility is not known. The purpose of this study was to investigate these
      relationships. METHOD: A convenience sample of 87 patients with stroke was
      recruited from an outpatient rehabilitation clinic. Demographics and clinical
      history were collected, and patients answered questionnaires regarding functional
      status. Motor impairment was assessed using motor items of the National
      Institutes of Health Stroke Scale (NIHSS), and BMD was measured using dual energy
      X-ray absorptiometry. RESULTS: Mean BMD measured at the total hip was lower on
      the paretic side relative to the contralateral side (0.883 +/- 0.148 g/cm2 vs
      0.923 +/- 0.136 g/cm2;P < .001). Compared to patients without limitations in
      walking, those reporting limitations had lower BMD at the paretic total hip
      (0.808 +/- 0.141 g/cm2 vs 0.917 +/- 0.139 g/cm2;P = .001) and lower BMDZ scores (
      0.282 +/- 0.888 vs -0.028 +/- 0.813;P = .035). A significant correlation was
      found between mean BMD and the BMDZ score at the total hip on the paretic side
      and motor impairment in that lower extremity (r = -0.326,P = .003;r = -0.312,P =
      .004, respectively). CONCLUSION: In patients with stroke, BMD at the paretic hip
      correlated with motor impairment. Furthermore, ability to ambulate was shown to
      be a simple yet useful test to determine which individuals had increased bone
      loss at the paretic versus nonparetichip.

PMID- 22982830
TI  - Functional assessment of spatial neglect: a review of the Catherine Bergego scale
      and an introduction of the Kessler foundation neglect assessment process.
AB  - Spatial neglect is a debilitating poststroke neurocognitive disorder associated
      with prolonged hospitalization and poor rehabilitation outcomes. The literature
      suggests a high prevalence of this disorder, but clinicians have difficulty
      reliably identifying affected survivors. This discrepancy may result from
      suboptimal use of validated neglect assessment procedures. In this article, we
      suggest use of a validated assessment tool that is sensitive to identification of
      neglect and its functional consequences - the Catherine Bergego Scale (CBS). We
      provide detailed item-by-item instructions for observation and scoring - the
      Kessler Foundation Neglect Assessment Process (KF-NAP). Rehabilitation
      researchers may be able to use the CBS via the KF-NAP to measure ecological
      outcomes and specific, separable perceptual-attentional and motor-exploratory
      spatial behaviors.

PMID- 22982832
TI  - Current and future interventions for glenohumeral subluxation in hemiplegia
      secondary to stroke.
AB  - Poststroke shoulder pain is a common issue and can be caused by glenohumeral
      subluxation. This entity hinders function and quality of life and is caused by
      changes in tone and loss of fi ne control of the shoulder joints' supporting
      structures after a stroke. Current treatments are limited in number and
      effectiveness and have significant problems and limitations to their use.
      Furthermore, prior to percutaneous implantable neuromuscular electrical
      stimulation, there was no evidence for any treatment to provide relief for
      chronic hemiplegic shoulder pain from glenohumeral subluxation. This clinical
      review provides a comprehensive review of the anatomy, pathogenesis, clinical
      features, management, and clinical efficacy of current treatment modalities.

PMID- 22982833
TI  - Special issue introduction: building a stronger science of community-engaged
      research.

PMID- 22982838
TI  - Connecting Boston's public housing developments to community health centers:
      who's ready for change?
AB  - BACKGROUND: Despite close proximity to community health centers, public housing
      residents are at increased risk of uncontrolled chronic disease, in part because
      of underutilization of routine health care. OBJECTIVES: To assist in program
      planning, the Partners in Health and Housing Prevention Research Center (PHH-PRC)
      used the Community Readiness Model to compare readiness of public housing
      developments and community health centers to address community-identified health
      priorities. The model assumes that program success to affect change depends on
      matching the community's level of readiness to address the issue. METHODS: Key
      respondent interviews were conducted across 15 communities: Eight housing
      developments and seven health centers. Interviews were scored across six
      dimensions on an anchored, 9-point scale and averaged to provide a composite
      readiness score. Higher scores indicate increasing levels of readiness. Interview
      transcripts were reviewed for consistent themes. RESULTS: Health centers scored
      significantly higher (mean, 5.88) than housing developments (mean, 3.33),
      corresponding with the Preparation stage of readiness compared with the Vague
      Awareness stage, respectively. Both scored highest in Existing Programs and
      Resources and lowest in Knowledge of Efforts. Qualitative analysis revealed a
      lack of existing partnerships between housing developments and health centers as
      well as significant social barriers preventing housing residents from engaging in
      care. CONCLUSION: We found a mismatch in readiness to address community health
      priorities. Although health centers have programs to address health issues,
      community awareness of programs is limited and barriers to engaging in care
      persist. The model provided a useful tool for engaging communities into shared
      program planning.

PMID- 22982839
TI  - Assessing an intervention to improve clinical trial perceptions among
      predominately African-American communities in South Carolina.
AB  - BACKGROUND: African Americans (AA) are not well-represented in cancer clinical
      trials despite having significantly higher cancer mortality rates than their
      European-American (EA) counterparts. OBJECTIVES: The purpose of this study was to
      evaluate a program to improve perceptions of cancer clinical trials among AA.
      METHODS: The program was conducted in a convenience sample of 195 participants
      (75.4% AA) who lived in counties with high racial disparities in cancer mortality
      rates and who were recruited by community partners. The 30-minute program, part
      of a larger 3.5-hour cancer education program, was developed by the National
      Institutes of Health (NIH)/National Cancer Institute (NCI). It was modified to
      include additional pictures of AA, AA-specific cancer mortality data, and
      information about the Tuskegee Syphilis Study and the resulting improved
      participant protection measures. MEASURES: The seven-item Attitudes to Randomized
      Trial Questionnaire (ARTQ) was used to evaluate changes in trial perceptions from
      pre- to posttest. Additional survey items assessed general demographic
      characteristics. RESULTS: Slightly more than half of the participants had at
      least a college diploma (54.4%), 45.1% were married/living as married, 53.3% were
      female, and 45.6% had an annual household income of less than $40,000. For each
      ARTQ item, most participants who had less favorable perceptions of trials at
      pretest changed to more positive perceptions at posttest (p < .001). CONCLUSIONS:
      Providing cancer clinical trial information led to more positive perceptions of
      cancer clinical trials. In future studies, the program could be used to help
      potential trial participants make informed decisions about participation; trial
      enrollment rates could then be evaluated.

PMID- 22982841
TI  - Leveraging community-academic partnerships to improve healthy food access in an
      urban, Kansas City, Kansas, community.
AB  - BACKGROUND: Americans can combat overweight (OW) and obesity by eating
      unprocessed, fresh foods. However, all Americans do not have equal access to
      these recommended foods. Low-income, minority, urban neighborhoods in particular
      often have limited access to healthy resources, although they are vulnerable to
      higher levels of OW and obesity. OBJECTIVE: This project used community-based
      participatory research (CBPR) principles to investigate the food needs of
      residents and develop a business plan to improve access to healthy food options
      in an urban, Kansas City, Kansas, neighborhood. METHODS: Partner community
      organizations were mobilized to conduct a Community Food Assessment survey. The
      surveys were accompanied by flyers that were part of the communication engagement
      strategy. Statistical analysis of the surveys was conducted. We engaged low
      income, minority population (40% Latino, 30% African American) urban communities
      at the household level. RESULTS: Survey results provided in-depth information
      about residents' food needs and thoughts on how to improve food access. Results
      were reported to community members at a town hall style meeting. LESSONS LEARNED:
      Developing a strategic plan to engage a community and develop trust is crucial to
      sustaining a partnership particularly when working with underserved communities.
      This project demonstrates that, if well managed, the benefits of academic and
      community partnerships outweigh the challenges thus such relationships should be
      encouraged and supported by communities, academic institutions, local and
      national government, and funders. CONCLUSION: A CBPR approach to understanding an
      urban community's food needs and opinions is important for comprehensive food
      access planning.

PMID- 22982840
TI  - Results from an intervention to improve rural home food and physical activity
      environments.
AB  - BACKGROUND: Ecological models of healthy eating and physical activity emphasize
      the influence of behavioral settings such as homes and worksites in shaping
      behavior. Research on home environments suggests that both social and physical
      aspects of the home may impact physical activity and healthy eating. OBJECTIVE:
      Using a community-based participatory research (CBPR) approach, the Emory
      Prevention Research Center (EPRC), Cancer Coalition of South Georgia, and the
      EPRC's Community Advisory Board (CAB) designed and tested a coach-based
      intervention to make the home environment more supportive of healthy eating and
      physical activity for rural adults. METHODS: The 6-week intervention consisted of
      a tailored home environment profile, goal-setting, and behavioral contracting
      delivered through two home visits and two telephone calls. The study used a quasi
      experimental design with data collected via telephone interviews at baseline, 2
      and 4 months post-baseline. Ninety households (n = 90) completed all three
      telephone interviews. RESULTS: Multilevel models indicated that intervention
      households reported significant improvements in household food inventories,
      purchasing of fruit and vegetables, healthier meal preparation, meals with the TV
      off, and family support for healthy eating, relative to comparison households.
      Intervention households also reported increased exercise equipment and family
      support for physical activity relative to comparison households. Percent of fat
      intake decreased significantly, but no changes were observed for fruit and
      vegetable intake, physical activity, or weight among intervention relative to
      comparison households, although trends were generally in a positive direction.
      CONCLUSION: Coaching combined with a focus on the home environment may be a
      promising strategy for weight gain prevention in adults.

PMID- 22982842
TI  - Evaluating community-based participatory research to improve community-partnered
      science and community health.
AB  - BACKGROUND: Since 2007, the National Congress of American Indians (NCAI) Policy
      Research Center (PRC) has partnered with the Universities of New Mexico and
      Washington to study the science of community-based participatory research (CBPR).
      Our goal is to identify facilitators and barriers to effective community-academic
      partnerships in American Indian and other communities, which face health
      disparities. OBJECTIVES: We have described herein the scientific design of our
      National Institutes of Health (NIH)-funded study (2009-2013) and lessons learned
      by having a strong community partner leading the research efforts. METHODS: The
      research team is implementing a mixed-methods study involving a survey of
      principal investigators (PIs) and partners across the nation and in-depth case
      studies of CBPR projects. RESULTS: We present preliminary findings on methods and
      measures for community-engaged research and eight lessons learned thus far
      regarding partnership evaluation, advisory councils, historical trust, research
      capacity development of community partner, advocacy, honoring each other,
      messaging, and funding. CONCLUSIONS: Study methodologies and lessons learned can
      help community-academic research partnerships translate research in communities.

PMID- 22982844
TI  - Community-researcher partnerships at NIAID HIV/AIDS clinical trials sites:
      insights for evaluation and enhancement.
AB  - BACKGROUND: Community engagement has been a cornerstone of National Institute of
      Allergy and Infectious Diseases (NIAID)'s HIV/AIDS clinical trials programs since
      1990. Stakeholders now consider this critical to success, hence the impetus to
      develop evaluation approaches. OBJECTIVES: The purpose was to assess the extent
      to which community advisory boards (CABs) at HIV/AIDS trials sites are being
      integrated into research activities. METHODS: CABs and research staff (RS) at
      NIAID research sites were surveyed for how each viewed (a) the frequency of
      activities indicative of community involvement, (b) the means for identifying,
      prioritizing, and supporting CAB needs, and (c) mission and operational
      challenges. RESULTS: Overall, CABs and RS share similar views about the frequency
      of community involvement activities. Cluster analysis reveals three groups of
      sites based on activity frequency ratings, including a group notable for CAB-RS
      discordance. CONCLUSIONS: Assessing differences between community and researcher
      perceptions about the frequency of and challenges posed by specific engagement
      activities may prove useful in developing evaluation tools for assessing
      community engagement in collaborative research settings.

PMID- 22982845
TI  - Engaging the Deaf American sign language community: lessons from a community
      based participatory research center.
AB  - BACKGROUND: Numerous publications demonstrate the importance of community-based
      participatory research (CBPR) in community health research, but few target the
      Deaf community. The Deaf community is understudied and underrepresented in health
      research despite suspected health disparities and communication barriers.
      OBJECTIVES: The goal of this paper is to share the lessons learned from the
      implementation of CBPR in an understudied community of Deaf American Sign
      Language (ASL) users in the greater Rochester, New York, area. METHODS: We review
      the process of CBPR in a Deaf ASL community and identify the lessons learned.
      RESULTS: Key CBPR lessons include the importance of engaging and educating the
      community about research, ensuring that research benefits the community, using
      peer-based recruitment strategies, and sustaining community partnerships. These
      lessons informed subsequent research activities. CONCLUSIONS: This report focuses
      on the use of CBPR principles in a Deaf ASL population; lessons learned can be
      applied to research with other challenging-to-reach populations.

PMID- 22982846
TI  - Let's Get Healthy! Health awareness through public participation in an education
      and research exhibit.
AB  - BACKGROUND: Health information technology (HIT) offers a resource for public
      empowerment through tailored information. OBJECTIVE: Use interactive community
      health events to improve awareness of chronic disease risk factors while
      collecting data to improve health. METHODS: Let's Get Healthy! is an education
      and research program in which participants visit interactive research stations to
      learn about their own health (diet, body composition, blood chemistry). HIT
      enables computerized data collection that presents participants with immediate
      results and tailored educational feedback. An anonymous wristband number links
      collected data in a population database. RESULTS AND LESSONS LEARNED: Communities
      tailor events to meet community health needs with volunteers trained to conduct
      research. Participants experience being a research participant and contribute to
      an anonymous population database for both traditional research purposes and open
      source community use. CONCLUSIONS: By integrating HIT with community involvement,
      health fairs become an interactive method for engaging communities in research
      and raising health awareness.

PMID- 22982847
TI  - Community-responsive research priorities: health research infrastructure.
AB  - THE PROBLEM: A disconnect exists between research resources and the health and
      health care needs of people those resources are designed to serve. While a great
      deal of research is being produced at academic institutions across the country,
      the topics investigated are often driven by researchers' interests or by funding
      announcements focused on specific research areas of interest to the funder.
      PURPOSE OF THE ARTICLE: The purpose of this article is to describe a process that
      connects community identified health priorities with research funds as well as
      capacity building efforts. KEY POINTS: The North Carolina Translational and
      Clinical Sciences Institute (NC TraCS) developed a process to identify the health
      priorities of North Carolina communities through a partnership with the network
      of county Healthy Carolinians partnerships. The priorities identified were
      obesity, youth issues, healthcare delivery/access, mental health/ substance
      abuse, specific chronic diseases, cancer/tobacco, and injury/ violence. NC TraCS
      then used these research priorities to guide pilot funding and facilitate
      research capacity building. CONCLUSIONS: Tapping into an established community
      based network and linking researchers to community-identified priorities ensures
      that NC TraCS addresses the most pressing health needs of North Carolina's
      residents.

PMID- 22982848
TI  - Community capacity building and sustainability: outcomes of community-based
      participatory research.
AB  - BACKGROUND: For communities, the value of community-based participatory research
      (CBPR) is often manifested in the outcomes of increased capacity and sustainable
      adoption of evidence-based practices for social change. Educational opportunities
      that promote discourse between community and academic partners can help to
      advance CBPR and better define these outcomes. OBJECTIVES: This paper describes a
      community-academic conference to develop shared definitions of community capacity
      building and sustainability related to CBPR and to identify obstacles and
      facilitators to both. METHODS: "Taking It to the Curbside: Engaging Communities
      to Create Sustainable Change for Health" was planned by five Clinical
      Translational Science Institutes and four community organizations. After a
      keynote presentation, breakout groups of community and academic members met to
      define community capacity building and sustainability, and to identify
      facilitators and barriers to achieving both. Groups were facilitated by
      researcher-community partner teams and conversations were recorded and
      transcribed. Qualitative analysis for thematic content was conducted by a subset
      of the planning committee. RESULTS: Important findings included learning that (1)
      the concepts of capacity and sustainability were considered interconnected; (2)
      partnership was perceived as both a facilitator and an outcome of CBPR; (3)
      sustainability was linked to "transfer of knowledge" from one generation to
      another within a community; and (4) capacity and sustainability were enhanced
      when goals were shared and health outcomes were achieved. CONCLUSIONS: Community
      capacity building and sustainability are key outcomes of CBPR for communities. Co
      learning opportunities that engage and mutually educate both community members
      and academics can be useful strategies for identifying meaningful strategies to
      achieve these outcomes.

PMID- 22982849
TI  - Quantitative assessment of participant knowledge and evaluation of participant
      satisfaction in the CARES training program.
AB  - BACKGROUND: The purpose of the Community Alliance for Research Empowering Social
      change (CARES) training program was to (1) train community members on evidence
      based public health, (2) increase their scientific literacy, and (3) develop the
      infrastructure for community-based participatory research (CBPR). OBJECTIVES: We
      assessed participant knowledge and evaluated participant satisfaction of the
      CARES training program to identify learning needs, obtain valuable feedback about
      the training, and ensure learning objectives were met through mutually beneficial
      CBPR approaches. METHODS: A baseline assessment was administered before the first
      training session and a follow-up assessment and evaluation was administered after
      the final training session. At each training session a pretest was administered
      before the session and a posttest and evaluation were administered at the end of
      the session. After training session six, a mid-training evaluation was
      administered. We analyze results from quantitative questions on the assessments,
      pre- and post-tests, and evaluations. RESULTS: CARES fellows knowledge increased
      at follow-up (75% of questions were answered correctly on average) compared with
      baseline (38% of questions were answered correctly on average) assessment; post
      test scores were higher than pre-test scores in 9 out of 11 sessions. Fellows
      enjoyed the training and rated all sessions well on the evaluations. CONCLUSIONS:
      The CARES fellows training program was successful in participant satisfaction and
      increasing community knowledge of public health, CBPR, and research methodology.
      Engaging and training community members in evidence-based public health research
      can develop an infrastructure for community-academic research partnerships.

PMID- 22982850
TI  - Creating a practice-based research network from scratch: where do I begin?
AB  - BACKGROUND: As of today, 50% of Clinical and Translational Science Award (CTSA)
      funded Academic Health Centers are engaging community clinicians through the
      practice-based research network (PBRN) mechanism, which has been identified as a
      best practice by the CTSA National Leadership. A PBRN is an organization of
      community clinicians who work together with researchers to answer meaningful
      questions that will improve patient care. METHODS: This paper outlines the steps
      that were led to success during the University of Texas Health Science Center at
      San Antonio's journey of developing four PBRNs over 3 years: (1) identifying
      network directors; (2) deciding who to include; (3) obtaining recruitment lists;
      (4) sending out mailers; (5) hosting the first PBRN meeting; (6) gaining
      institutional review board (IRB) approval; (7) launching a simple study; (8)
      returning the findings; and (9) formalizing the PBRN and moving forward. RESULTS:
      CTSAs will continue to seek ways to effectively engage community members in the
      clinical translation process. CONCLUSIONS: PBRNs are a promising laboratory for
      generating research questions directly from clinicians, conducting meaningful
      research, and then disseminating the findings to the larger community to
      accelerate positive change.

PMID- 22982851
TI  - A community translational research pilot grants program to facilitate community-
      academic partnerships: lessons from Colorado's clinical translational science
      awards.
AB  - BACKGROUND: National growth in translational research has increased the need for
      practical tools to improve how academic institutions engage communities in
      research. METHODS: One used by the Colorado Clinical and Translational Sciences
      Institute (CCTSI) to target investments in community-based translational research
      on health disparities is a Community Engagement (CE) Pilot Grants program.
      Innovative in design, the program accepts proposals from either community or
      academic applicants, requires that at least half of requested grant funds go to
      the community partner, and offers two funding tracks: One to develop new
      community-academic partnerships (up to $10,000), the other to strengthen existing
      partnerships through community translational research projects (up to $30,000).
      RESULTS AND CONCLUSION: We have seen early success in both traditional and
      capacity building metrics: the initial investment of $272,742 in our first cycle
      led to over $2.8 million dollars in additional grant funding, with grantees
      reporting strengthening capacity of their community- academic partnerships and
      the rigor and relevance of their research.

PMID- 22982854
TI  - Celiac disease:  a medical puzzle.
AB  - OVERVIEW: Celiac disease is a T-cell-mediated, autoimmune, genetic illness that
      targets the small intestine and typically resolves with removal of gluten from
      the diet. More widespread serologic testing indicates that celiac disease affects
      0.5% to 1% of the U.S. population, but presentation is highly variable and
      diagnosis is often missed or delayed. Strict adherence to a gluten-free diet
      remains the only treatment but can be challenging. This article outlines the
      pathophysiology of celiac disease, discusses signs and symptoms and the four
      disease types, describes testing, and addresses treatment and nursing
      implications.

PMID- 22982852
TI  - Partnership for implementation of evidence-based mental health practices in rural
      federally qualified health centers: theory and methods.
AB  - BACKGROUND: Mental health and substance abuse are among the most commonly
      reported reasons for visits to Federally Qualified Health Centers (CHCs), yet
      only 6.5% of encounters are with on-site behavioral health specialists. Rural
      CHCs are significantly less likely to have on-site behavioral specialists than
      urban CHCs. Because of this lack of mental health specialists in rural areas, the
      most promising approach to improving mental health outcomes is to help rural
      primary care (PC) providers deliver evidence-based practices (EBPs). Despite the
      scope of these problems, no research has developed an effective implementation
      strategy for facilitating the adoption of mental health EBPs for rural CHCs. We
      sought to describe the conceptual components of an implementation partnership
      that focuses on the adaption and adoption of mental health EBPs by rural CHCs in
      Arkansas. METHODS: We present a conceptual model that integrates seven separate
      frameworks: (1) Jones and Wells' Evidence-Based Community Partnership Model, (2)
      Kitson's Promoting Action on Research Implementation in Health Services (PARiHS)
      implementation framework, (3) Sackett's definition of evidence-based medicine,
      (4) Glisson's organizational social context model, (5) Rubenstein's Evidence
      Based Quality Improvement (EBQI) facilitation process, (6) Glasgow's RE-AIM
      evaluation approach, and (7) Naylor's concept of shared decision making.
      CONCLUSIONS: By integrating these frameworks into a meaningful conceptual model,
      we hope to develop a successful implementation partnership between an academic
      health center and small rural CHCs to improve mental health outcomes. Findings
      from this implementation partnership should have relevance to hundreds of clinics
      and millions of patients, and could help promote the sustained adoption of EBPs
      across rural America.

PMID- 22982855
TI  - Being young, female, and BRCA positive.
AB  - OBJECTIVE: Women who carry a BRCA1 or BRCA2 gene mutation face a risk of
      developing breast or ovarian cancer at an earlier age than women without such a
      mutation. Relatively little is known about the psychosocial consequences
      especially regarding marriage and childbearing-in young women who test positive
      for one of these mutations. METHODS: In 2006, participants were recruited from
      Web sites for women with breast cancer or BRCA gene mutations. Forty-four women
      ages 18 to 39 from 22 states and Canada who had had genetic testing and were
      found to carry a BRCA mutation were interviewed by phone or e-mail. A
      qualitative, grounded theory analysis was performed on the data, focusing on the
      participants' being young and having had genetic testing for the BRCA mutation.
      The findings reported here focus on three characteristics of the participants
      whether or not they were married, had children, or had a breast cancer diagnosis
      and how those characteristics were affected by the women's knowledge of their
      genetic risk. RESULTS: Among the 13 unmarried participants, issues of when to
      disclose information about their genetic risk in intimate relationships were
      discussed. Many of the 24 participants who had children reported "staying alive"
      for their children as a primary goal; the childless women reported an urgency to
      have children. Of the 21 who had a breast cancer diagnosis, the youngest was 24
      years old, and several said knowledge of their genetic risk influenced their
      decision to have the unaffected breast removed prophylactically. CONCLUSIONS: A
      sense of being different and not understood was expressed in these interviews.
      These findings suggest that nurses should be aware of psychosocial issues,
      especially those surrounding marriage and childbearing, in their interactions
      with young women who carry a BRCA1 or BRCA2 gene mutation.

PMID- 22982856
TI  - Rosiglitazone prevents graft-versus-host disease (GVHD).
AB  - The effect of rosiglitazone, an agonist of peroxisome proliferator-activated
      receptor-gamma (PPARgamma), was investigated in a mouse parent-to-F1 GVHD model.
      Rosiglitazone inhibited mixed lymphocyte reactions, inducing enhanced apoptosis
      in CD4+, CD8+, and B220+ cells, but not in NK1.1+, Mac-1+, CD4+/CD25+ and
      CD3+/NK1.1+ cells. Rosiglitazone administration prevented GVHD in the liver,
      skin, spleen and intestine. Rosiglitazone inhibited GVHD-induced increases in
      serum levels of tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)
      6, and IL-12, and the GVHD-induced decreases in transforming growth factor-beta
      and IL-10. Immunophenotyping of splenic leukocytes demonstrated that while
      rosiglitazone treatment increased the population percentages of both donor and
      host CD4+/CD25+ and CD3+/NK1.1+ cells, the treatment resulted in lower fractions
      of both donor and host CD8+ cells. Rosiglitazone inhibited the GVHD-induced
      decreases in the expression of phosphatase and tensin homologue deleted on
      chromosome 10 (PTEN), as well as the GVHD-induced increase in the splenic p-Akt
      and nuclear factor-kappa B expression. These results indicate that rosiglitazone
      and PPARgamma activation may be useful in protecting the host from GVHD.

PMID- 22982857
TI  - Glutathione promotes prostaglandin H synthase (cyclooxygenase)-dependent
      formation of malondialdehyde and 15(S)-8-iso-prostaglandin F2alpha.
AB  - Prostaglandin (PG) H synthases (PGHS) or cyclooxygenases (COX) catalyse the
      peroxidation of arachidonic acid (AA) to PGG(2) and PGH(2) which are further
      converted to a series of prostaglandins and thromboxane A(2). Here, we report
      that GSH promotes concomitant formation of the current oxidative stress
      biomarkers malondialdehyde (MDA) and 15(S)-8-iso-prostaglandin F(2alpha) from AA
      via PGHS. This illustrates an uncommon interplay of enzymatic and chemical
      reactions to produce species that are considered to be exclusively produced by
      free-radical-catalysed reactions. We propose mechanisms for the PGHS/AA/GSH
      dependent formation of MDA, 15(S)-8-iso-prostaglandin F(2alpha) and other F(2)
      isoprostanes. These mechanisms are supported by clinical observations.

PMID- 22982858
TI  - Enhanced phosphoserine insertion during Escherichia coli protein synthesis via
      partial UAG codon reassignment and release factor 1 deletion.
AB  - Genetically encoded phosphoserine incorporation programmed by the UAG codon was
      achieved by addition of engineered elongation factor and an archaeal aminoacyl
      tRNA synthetase to the normal Escherichia coli translation machinery (Park et
      al., 2011) Science 333, 1151). However, protein yield suffers from expression of
      the orthogonal phosphoserine translation system and competition with release
      factor 1 (RF-1). In a strain lacking RF-1, phosphoserine phosphatase, and where
      seven UAG codons residing in essential genes were converted to UAA, phosphoserine
      incorporation into GFP and WNK4 was significantly elevated, but with an
      accompanying loss in cellular fitness and viability.

PMID- 22982859
TI  - The FKBP families of higher plants: Exploring the structures and functions of
      protein interaction specialists.
AB  - The FK506-binding proteins (FKBPs) are known both as the receptors for
      immunosuppressant drugs and as prolyl isomerase (PPIase) enzymes that catalyse
      rotation of prolyl bonds. FKBPs are characterised by the inclusion of at least
      one FK506-binding domain (FKBd), the receptor site for proline and the active
      site for PPIase catalysis. The FKBPs form large and diverse families in most
      organisms, with the largest FKBP families occurring in higher plants. Plant FKBPs
      are molecular chaperones that interact with specific protein partners to regulate
      a diversity of cellular processes. Recent studies have found that plant FKBPs
      operate in intricate and coordinated mechanisms for regulating stress response
      and development processes, and discoveries of new interaction partners expand
      their cellular influences to gene expression and photosynthetic adaptations. This
      review presents an examination of the molecular and structural features and
      functional roles of the higher plant FKBP family within the context of these
      recent findings, and discusses the significance of domain conservation and
      variation for the development of a diverse, versatile and complex chaperone
      family.

PMID- 22982860
TI  - 2'-OH of mRNA are critical for the binding of its codons at the 40S ribosomal P
      site but not at the mRNA entry site.
AB  - The roles of 2'-OH groups in the binding of mRNA to human ribosomes were studied
      using site-directed cross-linking. We found that both mRNA and mDNA analogues
      bearing a cross-linker can modify ribosomal proteins (rps) S3e and S2e at the
      mRNA entry site independently on tRNA presence, but only mRNA analogues were
      capable of a tRNA(Phe)-dependent binding to human ribosomes and cross-linking to
      rpS26e in the mRNA binding centre. Thus, 2'-OH groups of mRNA are unimportant for
      binding at the entry site but they are crucial for codon-anticodon interactions
      at the P site, implying the existence of mRNA-ribosome contacts that do not occur
      in bacteria.

PMID- 22982861
TI  - Transcriptional repression of TWIST1 gene by Prospero-related homeobox 1 inhibits
      invasiveness of hepatocellular carcinoma cells.
AB  - Prospero-related homeobox 1 (PROX1) is important for liver development and down
      regulation of this transcription factor in hepatocellular carcinoma (HCC) is
      associated with poor prognosis. We find that PROX1 expression is inversely
      correlated with the expression of epithelial-mesenchymal regulator TWIST1 in HCC
      cell lines and tumor tissues. We demonstrate that PROX1 directly binds to
      proximal promoter of TWIST1 gene to repress its transcription and inhibits its
      downstream target gene AKT2 expression which leads to reduction of cell migration
      and invasion. Moreover, PROX1 attenuates lung metastasis of HCC in vivo. These
      results support an anti-metastatic role of PROX1 via inhibiting TWIST1.

PMID- 22982862
TI  - Structural insights into the calcium-dependent interaction between calbindin-D28K
      and caspase-3.
AB  - The regulation of apoptosis involves a complicated cascade requiring numerous
      protein interactions including the pro-apoptotic executioner protein caspase-3
      and the anti-apoptotic calcium-binding protein calbindin-D28K. Using isothermal
      titration calorimetry, we show that calbindin-D28K binds caspase-3 in a Ca(2+)
      dependent fashion. Molecular docking and conformational sampling studies of the
      Ca(2+)-loaded capase-3/calbindin-D28K interaction were performed in order to
      isolate potentially crucial intermolecular contacts. Residues in the active site
      loops of caspase-3 and EF-hands 1 and 2 of calbindin-D28K were shown to be
      critical to the interaction. Based on these studies, a model is proposed to help
      understand how calbindin-D28K may deactivate caspase-3 upon binding.

PMID- 22982863
TI  - Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat
      brains.
AB  - Growing evidence suggests that Alzheimer disease (AD) origins in vascular
      lesions. As the crucial mediator of vascular pathology, angiotensin II-induced
      significant amyloid production in our laboratory, although amyloid neurotoxicity
      depended on phosphorylated tau (p-tau) in recent studies. In the present study, p
      tau levels were significantly elevated by central angiotensin II via glycogen
      synthase kinase 3beta (GSK 3beta) and other tau kinases. Moreover, angiotensin II
      induced cognitive impairment and tau phosphorylation was attenuated by losartan
      and a GSK 3beta inhibitor. These findings implicate Ang II as a crucial mediator
      of AD pathology and a link between cardiovascular events and AD.

PMID- 22982864
TI  - EDC4 interacts with and regulates the dephospho-CoA kinase activity of CoA
      synthase.
AB  - Coenzyme A synthase (CoAsy) is a bifunctional enzyme which facilitates the last
      two steps of Coenzyme A biogenesis in higher eukaryotes. Here we describe that
      CoAsy forms a complex with enhancer of mRNA-decapping protein 4 (EDC4), a central
      scaffold component of processing bodies. CoAsy/EDC4 complex formation is
      regulated by growth factors and is affected by cellular stresses. EDC4 strongly
      inhibits the dephospho-CoA kinase activity of CoAsy in vitro. Transient
      overexpression of EDC4 decreases cell proliferation, and further co-expression of
      CoAsy diminishes this effect. Here we report that EDC4 might contribute to
      regulation of CoA biosynthesis in addition to its scaffold function in processing
      bodies.

PMID- 22982865
TI  - Short curcumin treatment modulates oxidative stress, arginase activity, aberrant
      crypt foci, and TGF-beta1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon
      carcinogenesis in mice.
AB  - This study investigated the effect of short curcumin treatment, a natural
      antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in
      mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 +/- 6 per
      colon, 10 weeks after the first DMH injection and reached 67 +/- 12 per colon
      after 12 weeks. A high level of undifferentiated goblet cells and a weak
      apoptotic activity were shown in dysplastic ACF. The morphological alterations of
      colonic mucosa were associated to severe oxidative stress ratio with 43% increase
      in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric
      synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase
      activity (296%), leading to nitrosative stress and cell proliferation. Curcumin
      treatment, starting at week 10 post-DMH injection for 14 days, reduced the number
      of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved
      redox status by approximately 46%, compared to DMH-treated mice. Moreover,
      curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells
      differentiation. Interestingly, curcumin induced a parallel increase in TGF-beta1
      and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective
      effect of curcumin was driven by the reduction of arginase activity and
      nitrosative stress. The up regulation of TGF-beta1 and HES-1 expression by
      curcumin suggests for the first time, a potential interplay between these
      signalling pathways in the chemoprotective mechanism of curcumin.

PMID- 22982866
TI  - Detoxification of tabun at physiological pH mediated by substituted beta
      cyclodextrin and glucose derivatives containing oxime groups.
AB  - The ability of 13 beta-cyclodextrin and 2 glucose derivatives containing
      substituents with oxime groups as nucleophilic components to accelerate the
      degradation of tabun at physiological pH has been evaluated. To this end, a
      qualitative and a quantitative enzymatic assay as well as a highly sensitive
      enantioselective GC-MS assay were used. In addition, an assay was developed that
      provided information about the mode of action of the investigated compounds. The
      results show that attachment of pyridinium-derived substituents with an aldoxime
      group in 3- or 4-position to a beta-cyclodextrin ring affords active compounds
      mediating tabun degradation. Activities differ depending on the structure, the
      number, and the position of the substituent on the ring. Highest activity was
      observed for a beta-cyclodextrin containing a 4-formylpyridinium oxime residue in
      6-position of one glucose subunit, which detoxifies tabun with a half-time of
      10.2 min. Comparison of the activity of this compound with that of an analog in
      which the cyclodextrin ring was replaced by a glucose residue demonstrated that
      the cyclodextrin is not necessary for activity but certainly beneficial. Finally,
      the results provide evidence that the mode of action of the cyclodextrin involves
      covalent modification of its oxime group rendering the scavenger inactive after
      reaction with the first tabun molecule.

PMID- 22982867
TI  - MicroRNA: a toolkit fine-tuning the dyadic "fuzzy space"?

PMID- 22982868
TI  - Heparin and bone marrow-derived cell therapy: friend or foe?

PMID- 22982869
TI  - Mitofusin 2 joins the sarcoplasmic reticulum and mitochondria at the hip to
      sustain cardiac energetics.

PMID- 22982870
TI  - Endothelial cardiac cell therapy: large-animal studies and the elephant in the
      room.

PMID- 22982871
TI  - Biased DNA segregation and cardiac stem cell therapies.

PMID- 22982872
TI  - Reprogrammed cardiac fibroblasts to the rescue of heart failure.

PMID- 22982873
TI  - Translational success stories: development of direct thrombin inhibitors.
AB  - Anticoagulants are the cornerstone of therapy for conditions associated with
      arterial and venous thrombosis. Direct thrombin inhibitors (DTIs) are
      anticoagulants that bind to thrombin and block its enzymatic activity. The
      bivalent parenteral DTIs hirudin and bivalirudin were based on the observation
      that the salivary extracts of medicinal leeches prevented blood from clotting.
      Key events that facilitated the subsequent development of small molecule active
      site inhibitors, such as argatroban, were the observation that fibrinopeptide A
      had antithrombotic properties and determination of the crystal structure of
      thrombin. Hirudin and argatroban have found their niche for the treatment of
      patients with heparin-induced thrombocytopenia, whereas bivalirudin is approved
      as an alternative to heparin for patients undergoing percutaneous coronary
      intervention. The development of orally active direct thrombin inhibitors was
      challenging because of the need to convert water-soluble, poorly absorbable,
      active site inhibitors into fat-soluble prodrugs that were then transformed back
      to the active drug after intestinal absorption. Dabigatran etexilate was the
      first new oral anticoagulant to be approved for long-term anticoagulant treatment
      in 6 decades. This Review highlights the development of DTIs as a translational
      success story; an example in which the combination of scientific ingenuity,
      structure-based design, and rigorous clinical trials has created a new class of
      anticoagulants that has improved patient care.

PMID- 22982876
TI  - The age-old tale of skeletal muscle vasodilation: new ideas regarding erythrocyte
      dysfunction and intravascular ATP in human physiology.

PMID- 22982874
TI  - Structural identification and cardiovascular activities of oxidized
      phospholipids.
AB  - Free radical-induced oxidation of membrane phospholipids generates complex
      mixtures of oxidized phospholipids (oxPLs). The combinatorial operation of a few
      dozen reaction types on a few dozen phospholipid structures results in the
      production of a dauntingly vast diversity of oxPL molecular species. Structural
      identification of the individual oxPL in these mixtures is a redoubtable
      challenge that is absolutely essential to allow determination of the biological
      activities of individual species. With an emphasis on cardiovascular
      consequences, this Review focuses on biological activities of oxPLs whose
      molecular structures are known and highlights 2 diametrically opposite approaches
      that were used to determine those structures, that is, (1) the classic approach
      from bioactivity of a complex mixture to isolation and structural
      characterization of the active molecule followed by confirmation of the structure
      by unambiguous chemical synthesis and (2) hypothesis of products that are likely
      to be generated by lipid oxidation, followed by synthesis, and then detection in
      vivo guided by the availability of authentic standards, and last,
      characterization of biological activities. Especially important for the
      application of the second paradigm is the capability of LC-MS/MS and
      derivatizations to selectively detect and quantify specific oxPL in complex
      mixtures, without the need for their isolation or complete separation. This
      technology can provide strong evidence for identity by comparisons with pure,
      well-characterized samples available by chemical syntheses. Those pure samples
      are critical for determining the biological activities attributable to specific
      molecular species of oxPLs in the complex mixtures generated in vivo as a
      consequence of oxidative stress.

PMID- 22982877
TI  - Formation of primary sperm conjugates in a haplogyne spider (Caponiidae, Araneae)
      with remarks on the evolution of sperm conjugation in spiders.
AB  - Sperm conjugation, where two or more sperm are physically united, is a rare but
      widespread pheno-menon across the animal kingdom. One group well known for its
      different types of sperm conjugation are spiders. Particularly, haplogyne spiders
      show a high diversity of sperm traits. Besides individual cleistospermia, primary
      (synspermia) and secondary (coenospermia, "spermatophore") sperm conjugation
      occurs. However, the evolution of sperm conjugates and sperm is not understood in
      this group. Here, we look at how sperm are transferred in Caponiidae (Haplogynae)
      in pursuit of additional information about the evolution of sperm transfer forms
      in spiders. Additionally, we investigated the male reproductive system and
      spermatozoa using light- and transmission electron-microscopy and provide a 3D
      reconstruction of individual as of well as conjugated spermatozoa. Mature
      spermatozoa are characterized by an extremely elongated, helical nucleus
      resulting in the longest spider sperm known to date. At the end of
      spermiogenesis, synspermia are formed by complete fusion of four spermatids.
      Thus, synspermia might have evolved early within ecribellate Haplogynae. The
      fused sperm cells are surrounded by a prominent vesicular area. The function of
      the vesicular area remains still unknown but might be correlated with the
      capacitation process inside the female. Further phylogenetic and functional
      implications of the spermatozoa and sperm conjugation are discussed.

PMID- 22982878
TI  - Giant and dwarf axons in a miniature insect, Encarsia formosa, (Hymenoptera,
      Calcididae).
AB  - Miniaturization effects in the central nervous system (CNS) of a very small
      calchicid wasp, Encarsia formosa (0.6 mm long), are obvious for the overall
      morphology and at the level of axon sizes. Parasagittal sections show that most
      ganglia are fused and leave connectives only in the neck and the petiole. The
      thoracic complex is partly squeezed between muscles, enwraps cuticular apodemes
      and protrudes laterally into the coxae of legs. Somata of neurons are similar in
      size and form a multiple layer around large neuropile regions of the CNS. In TEM
      sections of connectives the range of axon diameters lies between 0.045 and 3.8
      MUm. Extremely small axon diameters below 0.1 MUm are supposed to present spatial
      restrictions for ion channels and internal organelles. In theory, that can cause
      frequent spontaneous releases of action potentials (AP) which impede regular
      information transfer by normal APs. Therefore, axon sizes were studied in
      connectives between ganglia where longer distance information transfer requires
      action potentials even in the smallest axons. The diameters of many
      interganglionic axons below 0.08 MUm contradict the theory. The luxury of large
      axon diameters exceeding 2-3 MUm is reserved for several "giant" interneurons in
      the thoracic and in the abdominal ganglion complex. They should belong to rapid
      sensory alerting systems. The largest, a bilateral pair in the abdominal CNS,
      could integrate afferents from long wind sensitive hairs on the abdomen.

PMID- 22982880
TI  - Future research directions in sleep and ADHD: report of a consensus working
      group.
AB  - OBJECTIVE: To explore relationships between basic and translational science
      research regarding sleep and ADHD in children. METHOD: A multidisciplinary group
      of experts in pediatric sleep medicine and ADHD convened in November 2010 to
      summarize the current literature, delineate knowledge gaps, and formulate
      recommendations regarding future research directions and priorities. RESULTS: Six
      major research areas of interest were identified: (a) brain centers regulating
      sleep, arousal, and attention; (b) neurotransmitter systems involved in both
      sleep and attention regulation; (c) alterations of neural systems regulating
      sleep in ADHD; (d) phenotypic similarities between behavioral, mood, and
      cognitive manifestations of insufficient/disrupted sleep and ADHD; (e)
      hypoarousal and sleepiness in ADHD; and (f) external sleep-wake signals that
      affect sleep regulation in ADHD. CONCLUSION: An enhanced understanding of the
      complex mechanisms regulating sleep promotion, wakefulness, and attention may
      contribute to new insights regarding the core impairments in ADHD and lead to the
      development of new therapies.

PMID- 22982881
TI  - Characterization of a small cryptic plasmid pK50-2 isolated from Lactobacillus
      reuteri K50.
AB  - The complete nucleotide sequence of a cryptic plasmid, pK50-2, from Lactobacillus
      reuteri K50 had been determined. It consisted of an 1866 bp circular molecule
      with a G+C content of 35%, from which two putative open reading frames (orfs)
      could be predicted. Based on sequence similarity, the orf1 was not homologous to
      any known protein, while the N-terminus of the orf2 shared 56% and 64% identities
      with RepB proteins of plasmid pAR141 and an unnamed plasmid in L. reuteri strain
      PA-16, members of the rolling-circle replication (RCR) pMV158 family,
      respectively. Downstream of orf2, a sequence containing two conserved regions
      (i.e., bind and nick), possibly involved in the binding and nicking of Rep
      protein, similar to the dso (double strand origin) of RCR-pMV158 family was also
      identified. Furthermore, a sequence capable of forming the characteristic
      secondary structure of ssoT (single-strand origin type T) was subsequently
      determined upstream of the orf2 gene. Thus, the three elements essential for a
      RCR plasmid (i.e., dso, sso, and rep gene) were all deducible in the pK50-2.
      Noteworthy was that a conserved alpha helix-turn-alpha helix (HTH) motif, thus
      far only seen in theta-type plasmids, was for the first time identified in Rep
      protein of RCR plasmid, pK50-2. To estimate the pK50-2 could be an expression
      vector to deliver exogenous antigens, a shuttle vector pK50-S containing both
      pK50-2 and pUE80 (-) was used to analyze the segregational stability and copy
      number, which were shown that pK50-S in L. reuteri DSM 20016 were estimated to be
      98%, 77%, and 75% after 36, 72, and 100 generations and about 50 copies per
      chromosome equivalent by real-time PCR.

PMID- 22982882
TI  - Dynamic covalent templated-synthesis of [c2]daisy chains.
AB  - A couple of [c2]daisy chains have been assembled in each case from four
      components in quantitative yields at room temperature in acetonitrile as a result
      of the self-templated clippings of their [24]crown-8 rings by reversible imine
      bond formation around secondary dialkylammonium recognition sites in their
      stalks.

PMID- 22982883
TI  - Rare earth metal oxazoline complexes in asymmetric catalysis.
AB  - Polydentate oxazolines have been employed as highly effective stereodirecting
      ligands for asymmetric catalysis with metals from across most of the periodic
      table. Despite their highly versatile coordination chemistry, the use of these
      ligands tends to be polarised towards late transition metals; their use with
      early transition metals and the f-elements is significantly less developed. This
      current article aims to review the coordination chemistry and catalytic
      applications of Group 3 and lanthanide complexes supported by ligands possessing
      oxazoline moieties. Oxazoline-containing ligands were first employed in molecular
      lanthanide catalysis as early as 1997, yet there is still a significant void in
      the chemical literature in this respect. The ligands generally employed include
      bis(oxazolinyl)methane ("BOX"), 2,6-bis(oxazolinyl)pyridine ("pybox"), 1,1,1
      tris(oxazolinyl)ethane ("trisox"), and others. The complexes are employed in a
      wide-range of catalytic applications, especially in Lewis acid catalysis, but
      also in the stereospecific polymerisation of olefins.

PMID- 22982884
TI  - The effects of the urea-based herbicide linuron on reproductive endpoints in the
      fathead minnow (Pimephales promelas).
AB  - Linuron is a widely used urea-based herbicide that has anti-androgenic activity
      in both fish and rodents. To further elucidate the potential mode of action (MOA)
      of linuron on the vertebrate endocrine system, adult male and female fathead
      minnows were exposed for 21 days to dechlorinated water, a solvent control,
      17beta-estradiol (E2; 0.1 MUg/L), dihydrotestosterone (DHT; 100 MUg/L), linuron
      (1, 10, 100 MUg/L) and one co-treatment of DHT (100 MUg/L) and linuron (100
      MUg/L). There were no effects of linuron on egg hatching, 7 day egg survival,
      nuptial tubercle formation or gonadal histopathology. Administration of DHT and 1
      and 100 MUg/L linuron reduced plasma vitellogenin in females, while male plasma
      vitellogenin were induced after E2 exposure and co-exposure of DHT and linuron.
      Ovarian mRNA levels were examined for several genes involved in steroidogenesis
      (e.g. p450scc, cyp19a, star, tspo, hsd17b and hsd11b) and estrogen-mediated
      responses (esr1, esr2b, esr2a). Only p450scc mRNA was significantly decreased
      with DHT+linuron co-treatment. Clustering of steroidogenic mRNA transcript
      expression patterns revealed that patterns for linuron were more similar to E2
      compared to DHT. Collectively, this study supports the hypothesis that linuron
      may not be a pure anti-androgen and may have multiple MOAs that affect vertebrate
      reproduction.

PMID- 22982885
TI  - Multilocular cystic renal cell carcinoma: similarities and differences in
      immunoprofile compared with clear cell renal cell carcinoma.
AB  - Multilocular cystic renal cell carcinoma (RCC) is an uncommon renal neoplasm
      composed of thin fibrous septa lining multiple cystic spaces and associated with
      an excellent prognosis. Clear cells with generally low-grade nuclear features
      line the cystic spaces and may be present within the fibrous septa, although
      solid mass-forming areas are by definition absent. Despite the excellent
      prognosis, molecular-genetic alterations are similar to those of clear cell RCC.
      Immunohistochemical staining characteristics, however, have not been well
      elucidated. We studied 24 cases of multilocular cystic RCC, classified according
      to the 2004 World Health Organization System. Immunohistochemical analysis was
      performed using an automated immunostainer for CD10, cytokeratin 7 (CK7), alpha
      methylacyl-CoA-racemase, epithelial membrane antigen (EMA), cytokeratin CAM 5.2,
      carbonic anhydrase IX (CA-IX), estrogen/progesterone receptors, smooth muscle
      actin, PAX-2, and vimentin. Twenty-four cases of grade 1 to 2 clear cell RCC were
      stained for comparison. Multilocular cystic RCC and control cases of clear cell
      RCC showed the following results, respectively: CD10 (63%, 96%), CK7 (92%, 38%),
      alpha-methylacyl-CoA-racemase (21%, 67%), vimentin (58%, 33%), estrogen receptor
      (8%, 8%), CAM 5.2 (100%, 96%), EMA, CA-IX, PAX-2 (all 100%), and progesterone
      receptor (0%). Smooth muscle actin highlighted myofibroblastic cells within the
      septa of multilocular cystic RCC and the fine capillary vascular network of clear
      cell RCC. In summary, multilocular cystic RCC showed expression of common clear
      cell RCC markers CA-IX, EMA, and PAX-2, supporting the hypothesis that
      multilocular cystic RCC is a subtype of clear cell RCC. In contrast to clear cell
      RCC, tumors less frequently expressed CD10 (63% and often focal vs. 96% and
      diffuse) and more frequently expressed CK7 (92%), often diffusely (63%).
      Coexpression of CA-IX and CK7 represents a point of overlap with the recently
      described clear cell papillary RCC, which also may show a prominent cystic
      architecture. However, the latter lacks mutation of the VHL gene and deletion of
      chromosome 3p by molecular methodologies.

PMID- 22982886
TI  - Commercial molecular panels are of limited utility in the classification of
      pancreatic cystic lesions.
AB  - The PathfinderTG biomarker panel is useful in the evaluation of pancreatic cysts
      that have clinical features suspicious for malignancy, but its utility in
      classifying fine-needle aspiration biopsies from small pancreatic cystic lesions
      is yet to be proven. We used morphology to classify 20 pancreatic cyst cytology
      aspirates, all of which met radiographic criteria for close observation. Cases
      were cytologically classified as consistent with pseudocyst, serous cystadenoma,
      or mucinous neoplasm with low-grade, intermediate-grade, or high-grade dysplasia
      and analyzed for carcinoembryonic antigen. Redpath Integrated Pathology Inc.
      rendered diagnoses of nonmucinous (reactive/indolent or serous) or mucinous (low
      risk or at risk) cyst on the basis of results of the PathfinderTG panel (KRAS
      mutations, DNA content, and loss of heterozygosity at microsatellites linked to
      tumor suppressor genes). Cytologic and commercial laboratory diagnoses were
      concordant in only 7 (35%) cases. Seven cysts classified as mucinous with low
      grade dysplasia by cytology were interpreted as nonmucinous on the basis of the
      PathfinderTG panel, 2 of which were resected mucinous cysts. Two pancreatitis
      related pseudocysts were misdiagnosed as low-risk mucinous cysts; 1 mucinous cyst
      with low-grade dysplasia was considered at risk for neoplastic progression using
      the PathfinderTG panel. Only 1 cyst misclassified as pseudocyst by cytology, but
      low-risk mucinous cyst by molecular analysis, proved to be a mucinous cystic
      neoplasm with low-grade dysplasia after surgical resection. We conclude that the
      PathfinderTG panel may aid the classification of pancreatic lesions, but is often
      inaccurate and should not replace cytologic evaluation of these lesions.

PMID- 22982887
TI  - MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid
      fibrosarcoma: association with FUS gene rearrangement.
AB  - Sclerosing epithelioid fibrosarcoma (SEF) is a rare aggressive fibroblastic
      neoplasm composed of cords of epithelioid cells embedded in a dense collagenous
      stroma. The reported immunophenotype of SEF is nonspecific. Some SEF cases show
      morphologic and molecular overlap with low-grade fibromyxoid sarcoma (LGFMS),
      suggesting a relationship between these tumor types. MUC4 has recently been
      identified as a sensitive and specific marker for LGFMS; MUC4 expression was also
      observed in 2 tumors with hybrid features of SEF and LGFMS. We investigated MUC4
      expression in SEF and other epithelioid soft tissue tumors to determine (1) the
      potential diagnostic utility of MUC4 for SEF and (2) the association between MUC4
      expression and FUS rearrangement in SEF. Whole sections of 180 tumors were
      evaluated: 41 cases of SEF (including 29 "pure" SEF and 12 hybrid LGFMS-SEF), 20
      epithelioid sarcomas, 11 clear cell sarcomas, 11 metastatic melanomas, 10
      perivascular epithelioid cell tumors, 10 alveolar soft part sarcomas, 10
      epithelioid angiosarcomas, 10 epithelioid hemangioendotheliomas, 10 epithelioid
      gastrointestinal stromal tumors, 10 myoepithelial carcinomas, 17 ossifying
      fibromyxoid tumors, 10 leiomyosarcomas, and 10 biphasic synovial sarcomas.
      Immunohistochemical analysis was performed after antigen retrieval using a mouse
      anti-MUC4 monoclonal antibody. Fluorescence in situ hybridization (FISH) was
      performed on 33 SEF cases using FUS break-apart probes. A subset of cases was
      also evaluated for EWSR1 and CREB3L2/L1 rearrangements by FISH. Strong diffuse
      cytoplasmic staining for MUC4 was observed in 32 of 41 (78%) cases of SEF,
      including all 12 hybrid tumors. FUS rearrangement was detected in 8 of 21 (38%)
      MUC4-positive cases of SEF with successful FISH studies. The prevalence of FUS
      rearrangement was similar in hybrid LGFMS-SEF (2 of 6; 33%) and SEF without an
      LGFMS component (6 of 15; 40%). FUS rearrangement was not detected in any cases
      of MUC4-negative SEF. Two hybrid tumors had both EWSR1 and CREB3L1
      rearrangements. MUC4 expression was also seen in 9 of 10 (90%) biphasic synovial
      sarcomas, predominantly in the glandular component. All other tumor types were
      negative for MUC4, apart from focal reactivity in 5 ossifying fibromyxoid tumors,
      2 epithelioid gastrointestinal stromal tumors, and 1 myoepithelial carcinoma.
      MUC4 is a sensitive and relatively specific marker for SEF among epithelioid soft
      tissue tumors. MUC4 expression occurs more frequently than FUS rearrangement in
      SEF. The finding of EWSR1 and CREB3L1 rearrangements in 2 cases of hybrid LGFMS
      SEF suggests that SEFs are genetically heterogenous. MUC4-positive SEFs with FUS
      rearrangement are likely closely related to LGFMS. MUC4-positive SEFs that lack
      FUS rearrangement may be related to LGFMS but could have alternate fusion
      partners, including EWSR1. SEF without MUC4 expression may represent a distinct
      group of tumors. MUC4 expression correlates with glandular epithelial
      differentiation in biphasic synovial sarcoma and is very limited in other
      epithelioid soft tissue tumors.

PMID- 22982888
TI  - Massive neonatal adrenal enlargement due to cytomegaly, persistence of the
      transient cortex, and hyperplasia of the permanent cortex: findings in Cushing
      syndrome associated with hemihypertrophy.
AB  - Described in this article is the massive enlargement of both adrenal glands in 3
      newborns-2 girls and 1 boy. Two had hemihypertrophy and other congenital
      abnormalities but no identified genetic mutation; the third had genetically
      proven Beckwith-Wiedemann syndrome. Two had severe Cushing syndrome, the third
      had hypercortisolemia but no clinical Cushing syndrome. Bilateral adrenalectomy
      cured Cushing syndrome in the 2 with severe symptoms; total adrenal weight in
      these patients was 44 and 53 g, respectively. Unilateral adrenalectomy was
      performed in the third patient: the gland weighed 52 g; postoperatively, the
      patient's hypercortisolemia normalized, and, concomitantly, the enlarged
      contralateral adrenal gland had a 5-fold decrease in size with slight enlargement
      6 years postoperatively. Microscopically, the 3 patients had similar pathology:
      massive adrenal enlargement due to a combination of cytomegaly, persistence of
      the transient cortex, and hyperplasia of the permanent cortex. The pathologic
      findings were most likely the result of the genetic mutation identified in 1
      patient and of an unknown mutation in the remaining 2 patients.

PMID- 22982889
TI  - Identification of tissue contamination by polymorphic deletion probe fluorescence
      in situ hybridization.
AB  - Potential sources of error in surgical pathology include specimen
      misidentification, unidentified tissue, and tissue contamination of paraffin
      blocks and slides. Current molecular approaches to characterize unidentified or
      misidentified tissue include fluorescence in situ hybridization identification of
      sex chromosomes (XY FISH) and microsatellite analysis. Polymorphic deletion probe
      (PDP) FISH, a novel FISH assay based on copy number variants, can distinguish
      between cells and tissues from 2 individuals in situ, independent of gender.
      Using a panel of 3 PDPs, we compared the genotypes of potential tissue
      contaminants (n=19) and unidentified tissues (n=6) with patient tissues to
      determine the utility of PDP FISH in resolving specimen identity. XY FISH was
      added to increase the informative potential of the assay, and microsatellite
      analysis was used as a gold standard to confirm PDP FISH results. PDP FISH
      distinguished between putative contaminants and patient tissues in 13 of 14 cases
      and indicated a high likelihood of 2 tissues originating from the same source in
      11 of 11 cases. The assay has a sensitivity and specificity of 86% [6/7, exact
      95% confidence interval (CI): 42%, 97%] and 100% (9/9, exact 1-sided 97.5% CI:
      68%, 100%), respectively, and a positive predictive value and negative predictive
      value of 100% (6/6, exact 1-sided 97.5% CI: 54%, 100%) and 90% (9/10, exact 95%
      CI: 55%, 98%), respectively. PDP FISH is an accurate and practical molecular
      assay for the genetic characterization of potential tissue contaminants and
      unidentified tissues, especially in the setting of small sample size, and permits
      concomitant assessment of morphology.

PMID- 22982890
TI  - Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma
      from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix,
      anus, and lung.
AB  - Distinguishing invasive high-grade urothelial carcinoma (UC) from other
      carcinomas occurring in the genitourinary tract may be difficult. The
      differential diagnosis includes high-grade prostatic adenocarcinoma, spread from
      an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC. In
      terms of metastatic UC, the most common problem is differentiating spread of UC
      to the lung from a primary pulmonary SCC. Immunohistochemical analysis (IHC) for
      GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was
      performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade
      UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score
      >=8) prostatic adenocarcinomas, representative tissue sections from 15 invasive
      anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and
      TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with
      neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition,
      GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC
      metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell
      carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were
      positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC,
      respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases
      demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining.
      Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or
      uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high
      grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was
      present in occasional basal cells of benign prostate glands, in a few benign
      atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2
      (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining.
      Weak staining was also rarely observed in the benign anal squamous epithelium. Of
      the 31 uterine cervical carcinomas, 6 (19%) showed weak GATA3 staining (3
      nonfocal and 3 focal), and 2 (6%) demonstrated focal moderate staining. Twelve
      (80%) of the metastatic UCs to the lung were positive for GATA3, with 11 cases
      showing diffuse moderate or strong staining and 1 case showing focal moderate
      staining. None of the pulmonary SCCs or non-small cell carcinomas with squamous
      features was GATA3 positive. GATA3 IHC is a sensitive marker for UC, and positive
      staining in UC is typically nonfocal and moderate or strong in intensity. GATA3
      is also highly specific in excluding high-grade prostate adenocarcinoma. Although
      some cervical and anal SCCs can be GATA3 positive, unlike in UC, staining is more
      commonly focal and weak. GATA3 is also a useful maker when diagnosing metastatic
      UC to the lung.

PMID- 22982891
TI  - Tumor necrosis is a prognostic factor in thick cutaneous melanoma.
AB  - The significance of tumor necrosis in cutaneous melanoma has not been well
      elucidated. The purpose of this study was to explore the prognostic impact of
      necrosis in comparison with other known clinicopathologic factors in these
      tumors. Initially, 457 consecutive cases of nodular cutaneous melanoma (1981 to
      2008) were included in this series. Tumor necrosis was assessed on hematoxylin
      and eosin-stained sections and was recorded as significant when an area of at
      least a quarter of a high-power field (*400; 0.07 mm) was occupied by necrotic
      cells and as sparse when clusters of at least 5 necrotic cells were observed.
      Tumor necrosis (26% of the cases) was associated with increased tumor thickness,
      high mitotic count, presence of tumor ulceration, and decreased survival.
      Stratified analyses (univariate and multivariate) with standard microscopic
      variables indicated the strongest prognostic influence of necrosis in tumors
      thicker than 4 mm. Notably, in the stratum of pT4 tumors, presence of necrosis
      was a stronger prognostic predictor than was ulceration. Tumor necrosis was a
      significant prognostic indicator providing additional information to established
      predictors of patient outcome in this series of nodular cutaneous melanoma,
      predominantly among thick tumors (>4 mm). Presence of necrosis was a stronger
      indicator for worse outcome compared with ulceration in pT4 tumors.

PMID- 22982892
TI  - Evaluation of reliability of FISH versus brightfield dual-probe in situ
      hybridization (BDISH) for frontline assessment of HER2 status in breast cancer
      samples in a community setting: influence of poor tissue preservation.
AB  - AIMS: To evaluate the reliability of novel brightfield microscopy-based dual in
      situ hybridization (BDISH) methods for frontline HER2 status analysis in selected
      suboptimally preserved breast cancer tissue samples reflecting of the worst
      scenario in a community. METHODS AND RESULTS: A total of 320 morphologically
      poorly preserved breast invasive ductal carcinomas from the archives of 2
      tertiary institutions in Brazil were selected for a tissue microarray-based
      analysis. 4B5 antibody was used for immunohistochemistry. Fluorescence in situ
      hybridization (FISH), DuoCISH, ZytoDot CISH, and silver in situ hybridization
      (SISH) were performed and compared. The highest agreement was observed between
      SISH and FISH. In addition, SISH was easier to assess in both amplified and
      nonamplified cases when compared with the other chromogenic methods, due to the
      sharpness of its dots. DuoCISH produced false-positive results, associated with
      thicker ill-defined dots, causing poor distinction between nonamplification and
      low amplification. ZytoDot CISH showed lower sensitivity, with increased
      frequency of false-positive results. CONCLUSIONS: SISH is the most reliable of
      the BDISH methods, with sensitivity and specificity highly comparable with FISH.
      It is also less deleterious than other BDISH methods, producing signals that were
      more distinct and therefore more readily analyzable even in poorly preserved
      tissue.

PMID- 22982893
TI  - Chickenpox-related pulmonary granulomas in immunocompetent adults:
      clinicopathologic and molecular features of an underrated occurrence.
AB  - Pulmonary granulomas represent a common inflammatory reaction to several lung
      infective or noninfective diseases. However, little is known about the histology
      and clinical presentation of chickenpox-related granulomas in immunocompetent
      subjects. We collected a series of 8 adult patients (mean age, 40 y; range, 33 to
      53 y) with several bilateral pulmonary granulomas incidentally discovered after
      imaging studies. All patients were asymptomatic and had experienced a varicella
      zoster virus (VZV) infection as adults but were clinically suspected to have a
      metastatic neoplasm of unknown origin. Chest computed tomography scan revealed
      numerous, tiny (few millimeters to 1 cm in size) nodules randomly dispersed
      through the lungs. Positron emission tomography scan performed in 4 patients was
      negative. All patients underwent video-assisted thoracoscopic surgical resection
      and were still alive and well. At histology, granulomas consisted of well
      defined, rounded, small nodules centered by a deeply eosinophilic, acellular
      necrosis rimmed by lamellar dense collagen and a chronic inflammatory infiltrate
      with or without multinucleated giant cells. Chickenpox-related granulomas were
      included in the differential diagnosis along with several other granulomatous
      diseases. Polymerase chain reaction-based molecular analysis for VZV performed on
      paraffin sections detected VZV DNA in all 8 cases. By contrast, 85 cases of
      pulmonary granulomas of different etiologies were simultaneously studied by
      molecular analysis with negative results. Pathologists should be familiar with
      the peculiar morphologic appearance of chickenpox-related granulomas. A careful
      search for a history of VZV infection in adulthood and molecular studies may be
      very helpful in confirming the diagnosis.

PMID- 22982894
TI  - Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between
      mesotheliomas and pulmonary adenocarcinomas in clinical practice.
AB  - Most reports on antibodies that claimed to separate mesothelioma from pulmonary
      adenocarcinoma originated from academic centers or specialized
      immunohistochemistry laboratories, but little is known about how such stains
      perform in general practice laboratories. The Canadian Immunohistochemistry
      Quality Control program circulates tissue array slides to laboratories across
      Canada; these are stained and then interpreted by the local laboratory and by a
      set of experienced reviewers. For Canadian Immunohistochemistry Quality Control
      run 16, tissue array slides from 16 pulmonary adenocarcinomas and 6 mesotheliomas
      were stained in 36 different laboratories for CEA, CD15, CK5/6, and calretinin. A
      total of 736 results (cores) were interpretable. If 3 of 4 staining results
      concordant with the diagnosis was accepted as definitive, 166/192 (86.4%)
      mesothelioma cores and 461/544 (84.7%) adenocarcinoma cores were correctly
      diagnosed. However, if 4 of 4 concordant markers were required, then 93/192
      (48.4%) mesothelioma cores and 265/544 (48.7%) adenocarcinoma cores were
      correctly diagnosed. Only 3/192 (1.6%) mesothelioma cores were incorrectly
      classified as carcinomas and 8/544 (1.5%) of adenocarcinoma cores incorrectly
      classified as mesotheliomas on the basis of the immunoprofile (ie, 3 of 4 or 4 of
      4 marker results were discordant with the diagnosis). We conclude that, in a
      study based on results from nonspecialized laboratories, the combination of CEA,
      CD15, calretinin, and CK5/6, used as a panel, has a very low false-positive rate
      when separating pulmonary adenocarcinomas from mesotheliomas; however, single
      negative or incorrect results are common, therefore the panel is only useful
      diagnostically if 3 of 4 correct results are deemed acceptable for diagnosis.

PMID- 22982895
TI  - Fibrin-associated large B-cell lymphoma: part of the spectrum of cardiac
      lymphomas.
AB  - Cardiac lymphomas are rare, and the spectrum of pathologic features is not well
      defined. We encountered an unusual case of cardiac lymphoma residing within a
      presumed thrombus. To place such cases in context, we reviewed all cardiac
      lymphomas presenting to a large US cardiovascular medicine referral center during
      a 30-year period. A total of 14 cardiac lymphomas were identified, and these
      included 6 primary cardiac lymphomas (PCLs) and 8 lymphomas secondarily involving
      cardiac structures. Upon review, 3 of the PCLs were confirmed to be diffuse large
      B-cell lymphoma, not otherwise specified, involving the myocardium. The other 3
      cases of PCL lacked myocardial invasion and showed lymphoma cells embedded in
      fibrin thrombus. Acute inflammation was not evident. These lymphomas presented in
      immunocompetent male individuals and involved either a prolapsed myxomatous
      mitral valve, a pseudomyxoma from the left atrium, or a thrombus arising in a
      synthetic aortic root graft. All 3 consisted of large atypical lymphocytes
      expressing a nongerminal center B-cell immunophenotype. Two cases were positive
      for Epstein-Barr virus (latency type III), but none demonstrated human herpes
      virus-8 latent nuclear antigen. No systemic disease was found at presentation or
      during follow-up. In our experience, fibrin-associated large B-cell lymphoma
      arising in the heart represents a substantial proportion of PCL. These lymphomas
      appear to represent an underrecognized variant of diffuse large B-cell lymphoma
      with favorable outcome. Further study is needed to understand their natural
      history.

PMID- 22982896
TI  - alpha-Hemoglobin-stabilizing protein is a sensitive and specific marker of
      erythroid precursors.
AB  - alpha-Hemoglobin-stabilizing protein (AHSP) is an abundant erythroid-specific
      chaperone protein that facilitates incorporation of nascent alpha-globin into
      hemoglobin A. We characterized AHSP expression by immunohistochemistry in a panel
      of 100 neoplastic and reactive bone marrow biopsies and splenic tissue with
      extramedullary hematopoiesis and compared it with established erythroid markers
      CD71 and CD235a. In all cases, AHSP expression was limited to physiological
      nucleated erythroid precursors (EPs) and blasts in erythroid leukemias. Although
      CD71 also stained EPs, it additionally stained nonerythroid malignant cells to
      varying extents in acute leukemia, diffuse large B-cell lymphoma, metastatic
      carcinomas, and small round blue cell tumors. In contrast, CD235a staining was
      erythroid-specific but stained non-nucleated red blood cells in all specimens,
      limiting its utility. We conclude that AHSP is superior to CD71 and CD235a for
      detecting normal and neoplastic nucleated EPs.

PMID- 22982897
TI  - Diffuse pulmonary lymphatic disease presenting as interstitial lung disease in
      adulthood: report of 3 cases.
AB  - Diffuse pulmonary lymphatic diseases are typically diagnosed shortly after birth
      or in childhood, but rarely may become evident in adulthood. We report 3 adult
      patients who presented with diffuse interstitial lung disease clinically and
      radiologically but on biopsy were found to have diffuse pulmonary lymphatic
      disease (2 cases of pulmonary lymphangiectasis and 1 case of pulmonary
      lymphangiomatosis). These patients presented with the insidious onset of symptoms
      including shortness of breath and cough. Imaging studies of the chest showed
      diffuse pulmonary interstitial opacities, often with a perilymphatic
      distribution. The clinical differential diagnostic considerations before surgical
      lung biopsy included infection, neoplasm, and interstitial lung disease. The
      histopathologic features included abnormal vessels and associated fibrosis
      following lymphatic routes, namely visceral pleura, bronchovascular bundles, and
      interlobular septa. Lymphangiectasis was characterized by dilation of normally
      distributed lymphatic spaces, whereas lymphangiomatosis showed a complex
      anastamosing proliferation of lymphatic vascular spaces without significant
      dilatation. The dilated lymphatic spaces often had undergone muscularization,
      which could easily lead to misclassification as veins. Immunohistochemical
      staining for the lymphatic endothelial marker D2-40 was helpful in correctly
      classifying these lesions. Diffuse pulmonary lymphatic disease can rarely present
      in adulthood, wherein the histologic findings can be subtle and could be
      overlooked as nonspecific reactive changes or misdiagnosed as an idiopathic
      interstitial lung disease. Recognition of the characteristic lymphangitic
      distribution of abnormally dilated or reduplicated lymphatic spaces is key to the
      correct diagnosis.

PMID- 22982898
TI  - Sclerosing cholangitis with granulocytic epithelial lesion: a benign form of
      sclerosing cholangiopathy.
AB  - The association between autoimmune pancreatitis and sclerosing cholangitis has
      attracted considerable attention. In contrast to type 1 (IgG4-related) autoimmune
      pancreatitis, bile duct involvement is uncommon in type 2 autoimmune
      pancreatitis, a more benign condition characterized histologically by
      granulocytic epithelial lesions (GELs). Following our recent report on a child
      with GEL-positive sclerosing cholangitis and excellent response to steroids, we
      retrospectively reviewed the liver histology of a large number of patients with
      sclerosing cholangitis to investigate the possible role of type 2 autoimmune
      pancreatitis in this pathology. Liver biopsies of 103 children with autoimmune
      sclerosing cholangitis and 142 adults with primary sclerosing cholangitis were
      reviewed for the presence of neutrophilic bile duct injury. Histologic findings
      were correlated with clinical features, response to treatment, and outcome.
      Neutrophilic bile duct lesions similar to GEL were identified in 5 cases (4
      children and 1 adult; 4% of autoimmune sclerosing cholangitis and 0.7% of primary
      sclerosing cholangitis). GEL was more commonly seen in wedge biopsy specimens.
      One patient had concomitant pancreatitis. Cholangiograms showed diffuse
      stricturing of bile ducts in all cases. The number of liver tissue IgG4 plasma
      cells did not increase, and serum IgG4 levels were normal in 3 patients tested.
      All patients went into remission with prednisolone and/or ursodeoxycholic acid,
      and their liver function tests remained completely normal without relapses over a
      follow-up period of 6 to 16 years. Although rare, the diagnosis of sclerosing
      cholangitis with GEL is important in view of its excellent and apparently
      sustained response to immunosuppressive treatment.

PMID- 22982900
TI  - Cellular spindled histiocytic pseudotumor complicating mammary fat necrosis: a
      potential diagnostic pitfall.
AB  - Fat necrosis of the breast is a relatively common reactive/reparative process
      that may be either primary, often after trauma, or secondary to prior surgery or
      therapeutic irradiation. Mammary fat necrosis may closely mimic breast neoplasia,
      both clinically and radiographically, and is thus frequently biopsied. In the
      majority of cases fat necrosis in the breast shows classic morphologic features
      and is a straightforward diagnosis. However, over the past several years we have
      seen a number of more challenging cases of mammary fat necrosis complicated by a
      distinctive cellular, spindled proliferation of macrophages, mimicking various
      spindle cell neoplasms of the breast. Herein we report our experience with such
      lesions. A total of 118 cases of fat necrosis involving the breast were retrieved
      from our institutional and consultation archives for the period 1994 to 2011. The
      final study group of 20 cases included only (1) consultation cases submitted
      specifically with concern for a spindle cell neoplasm and (2) institutional cases
      presenting as a mass lesion and showing an identical spindle cell proliferation.
      The tumors occurred in 20 women (mean age 58 y; range, 24 to 70 y), involved both
      breasts (left, 11 cases; right, 9 cases), and ranged in size from 0.8 to 2.5 cm
      (mean 1.5 cm). Additional clinical information was available for 18 (90%)
      patients; a history of ipsilateral breast carcinoma and prior therapeutic
      irradiation were documented in 7 of 18 (39%) and 6 of 18 (33%) patients,
      respectively. Radiographic reports and/or imaging was available for 17 (85%)
      patients; radiographic impressions were "suspicious for malignancy" (10 cases,
      59%), "indeterminate" (2 cases, 12%), or "benign" (5 cases, 29%). The patients
      underwent core needle (14 cases, 70%) and excisional (6 cases, 30%) biopsies. The
      morphologic features of all cases were similar, showing a moderately cellular,
      fascicular proliferation of mitotically active, normochromatic, lightly
      eosinophilic spindled cells with mild nuclear variability, folded or grooved
      nuclei, and indistinct nucleoli. Chronic inflammatory cells and multinucleated
      giant cells were often admixed with the spindled cells, with more typical
      features of fat necrosis frequently present at the periphery. Immunohistochemical
      analysis performed at Mayo Clinic showed the lesional cells to express the
      histiocyte-associated markers CD163 (8 of 8, 100%), CD11c (8 of 8, 100%), and
      CD31 (4 of 8, 50%) and to be negative for keratins using the OSCAR monoclonal
      antibody (0 of 8, 0%). Studies conducted at outside institutions showed absent
      expression of various keratins, S100 protein, p63, and beta-catenin protein.
      Histochemical staining for mycobacterial and fungal organisms was negative.
      Follow-up (18 patients, 1 to 120 mo, mean 37 mo) showed all patients to be alive
      without disease. Additional surgical procedures (6 patients) showed only fat
      necrosis. We believe that these lesions represent an exaggerated histiocytic
      reaction to fat necrosis in the breast. Awareness of this distinctive pseudotumor
      should help to prevent its misdiagnosis as various other mammary spindle cell
      neoplasms.

PMID- 22982899
TI  - Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE
      FAM22 rearrangement.
AB  - Endometrial stromal sarcoma (ESS) characterized by YWHAE-FAM22 genetic fusion is
      histologically higher grade and clinically more aggressive than ESS with JAZF1
      SUZ12 or equivalent genetic rearrangements, hence it is clinically important to
      recognize this subset of ESS. To identify diagnostic immunomarkers for this
      biologically defined ESS subset, we compared gene expression profiles between
      YWHAE-FAM22 ESS and JAZF1-rearranged ESS. These studies showed consistent
      upregulation of cyclin D1 in YWHAE-FAM22 ESS compared with JAZF1-SUZ12 ESS.
      Immunohistochemically, the high-grade round cell component of all 12 YWHAE-FAM22
      ESS demonstrated diffuse (>=70%) moderate to strong nuclear cyclin D1 staining,
      and this diffuse positivity was not seen in 34 ESSs with JAZF1 and equivalent
      genetic rearrangements or in 21 low-grade ESS with no demonstrable genetic
      rearrangements. In a series of 243 non-ESS pure uterine mesenchymal and mixed
      epithelial-mesenchymal tumors, only 2 of 8 undifferentiated endometrial sarcomas
      with nuclear uniformity and 1 of 80 uterine leiomyosarcomas demonstrate diffuse
      cyclin D1 immunoreactivity. Both cyclin D1-positive undifferentiated endometrial
      sarcomas showed diffuse strong CD10 staining, which is consistently absent in the
      high-grade round cell component of YWHAE-FAM22 ESS. The low-grade spindle cell
      component of YWHAE-FAM22 ESS showed a spatially heterogenous cyclin D1 staining
      pattern that was weaker and less diffuse overall. Our findings indicate that
      cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22
      ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in
      the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS.

PMID- 22982901
TI  - Angiodysplastic lesions as a cause of colonic bleeding in patients with chronic
      renal disease: is there an association?
AB  - Gastrointestinal bleeding due to angiodysplastic lesions of the large bowel is a
      common problem among patients receiving hemodialysis and may sometimes be life
      threatening. Several hypotheses have been advanced in order to explain the
      increased incidence of these lesions in this cohort of patients, including
      degenerative, metabolic, circulatory and other systemic factors. In terms of
      diagnosis, several advances have been made with sophisticated techniques, but
      endoscopy seems to be the most effective, having a dual role in diagnosis and
      treatment. Although most bleeds stop spontaneously, conservative treatment may
      not be enough. Endoscopic treatment, embolization with infusion of vasopressin,
      surgical resection of the bleeding intestinal segment and hormone administration
      may be useful therapeutic tools.

PMID- 22982902
TI  - Attitude and willingness of high school students toward organ donation.
AB  - Public awareness of organ donation fundamentally affects the organ
      transplantation programs. This study was performed to assess the attitude and
      willingness of high school adolescents regarding organ donation. The study
      population consisted of 416 high school girls who were studying in four grades of
      three educational courses. Data were collected by a questionnaire and included
      demographic variables and attitude and willingness, which were assessed based on
      the Likert scale. The SPSS v.16 was used for data analysis. The mean age of the
      study subjects was 16.26 +/- 1.06 years, 31% studied in grade-1, 27% in grade-2
      (25% natural sciences, 27% mathematics and 48% humanities), 26% in grade-3 (30%
      natural sciences, 34% mathematics and 36% humanities) and 16% in pre-university
      stage (32% natural sciences, 42% mathematics and 26% humanities). The students
      had a highly positive attitude toward organ donation (mean score 4.2 +/- 0.54).
      The greatest willingness for organ donation was concerning the kidney (88%) and
      heart (84%), followed by the liver (83.4%), pancreas (79.6%), cornea (67.8%) and
      skin (51%). Willingness for deceased as well as living organ donation was
      indicated by 92% and 47%, respectively, of the participants. Organ donation was
      considered acceptable only to relatives by 5% of the participants when the donors
      were deceased donors and by 16% of the participants when the donors were living
      donors; donation to all needy persons from deceased donors was accepted by 87% of
      the participants and from living donors by 31%. The purpose of donation was
      stated as lending help to others by 89% and progression of science by 40.2% of
      the participants. Willingness for organ donation from a deceased relative was
      declared by 63% of the students. There was significant positive correlation
      between willingness for organ donation and attitude (P <0.001). In addition,
      attitude and willingness had positive correlation with educational levels, age
      and educational courses. Our study suggests that Iranian adolescents have a great
      attitude and willingness toward organ donation, which reflects favorable
      knowledge of transplantation. Further research on public awareness in both
      genders and various age ranges is needed.

PMID- 22982903
TI  - Comparison of efficacy of the phosphate binders nicotinic acid and sevelamer
      hydrochloride in hemodialysis patients.
AB  - Hyperphosphatemia is a significant risk factor for the development of ectopic
      calcification and coronary artery diseases in patients on hemodialysis (HD), and
      must be controlled with the use of phosphate binders. Studies comparing the
      effects of sevelamer and nicotinic acid, both similar non-calcium and non
      aluminum phosphate binders, are not available. In this study, 40 patients on HD
      with a serum phosphorus level of more than 6 mg/dL were enrolled. After a two
      week washout period without phosphate binders, the patients were randomly divided
      into two equal groups (n = 20) and were started on nicotinic acid or sevelamer
      for a period of four weeks. The dose of nicotinic acid used was 500 mg and that
      of sevelamer was 1600 mg daily. Blood samples were drawn for the measurement of
      the total calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), triglyceride
      (TG), total cholesterol (Chol), high-density lipoprotein (HDL), low-density
      lipoprotein (LDL), uric acid and parathyroid hormone (PTH). Patients receiving
      sevelamer showed a significant reduction in serum P level (2.2 +/- 0.69 mg/dL; P
      <0.0001) in comparison with the nicotinic acid group (1.7 +/- 1.06 mg/dL; P =
      0.004). Reduction in the Ca-P product was significantly different in the two
      groups; in the sevelamer group, it was 21 +/- 7; (P <0.0001) while in the
      nicotinic acid group, it was 16 +/- 11 (P = 0.007). Also, patients on sevelamer
      showed greater reduction in the mean TG level (38.9 +/- 92 mg/dL; P = 0.005). No
      significant changes were observed in the mean serum Ca, total Chol, HDL, LDL, ALP
      and iPTH levels in the two study groups. Our short-term study suggests that
      although nicotinic acid reduced hyperphosphatemia, sevelamer showed higher
      efficacy in controlling hyperphosphatemia as well as the Ca-P product.

PMID- 22982904
TI  - Predictive value of cardiac troponin T and I in hemodialysis patients.
AB  - Cardiac troponin T (cTnT) and I (cTnI) levels are considered as important
      diagnostic tools in acute coronary events. They could be of predictive value in
      hemodialysis (HD) patients. The aim of this study was to determine the prevalence
      of increased cTnI and cTnT in HD patients and their prognostic relevance to all
      cause mortality. We measured cTnT and cTnI at baseline in 145 asymptomatic HD
      patients. We used three different cut-off criteria to define elevated cardiac
      troponin levels as follows: the 99 th percentile of a reference population, the
      lowest concentration to give a 10% imprecision [10% coefficient of variation (10%
      CV)] and the relative operating characteristic (ROC) curve-determined value
      optimized for diagnostic sensitivity and specificity for detection of myocardial
      injury (MI). These concentrations were 0.01 ng/mL, 0.03 ng/mL and 0.1 ng/mL for
      cTnT and 0.2 ng/mL, 0.6 ng/mL and 1 ng/mL for cTnI, respectively. Patients were
      followed for all-cause mortality (median follow-up 551 days). Kaplan-Meier
      survival curves, log-rank test and Cox models were employed to determine whether
      baseline cTnT and cTnI levels were predictive of mortality. Greater percentages
      of patients had an increased cTnT versus cTnI at each cut-off as follows: 99 th
      percentile, 90.3% versus 35.2%; 10% CV, 73.1% versus 2.1%; and ROC, 20.7% versus
      0.7%. During follow-up, 40 patients died. Elevated cTnT levels above the ROC
      concentration were associated with increased mortality, although it was not
      significant after adjustment for other risk factors. Univariate and adjusted
      hazard ratios were 2.3 [confidence intervals (CI), 1.2-4.5; P = 0. 01] and 1.9
      (CI, 0.9-3.9; P = 0.07). No differences were found for cTnI levels. Diabetes
      mellitus was also an independent predictor of mortality. There is a high
      prevalence of positive cTnT and cTnI in asymptomatic HD patients, with a greater
      number of patients having an increased cTnT. Elevated troponin T, but not cTnI,
      seems to be associated with poor prognosis.

PMID- 22982905
TI  - Depression in patients on hemodialysis and their caregivers.
AB  - Depression is recognized as the most common psychiatric problem in patients with
      end-stage renal disease. Stress negatively affects the quality of life of not
      only the patients on hemodialysis but also their caregivers. The objective of
      this study was to measure and compare the frequency of depression in these
      patients and their attendants, and to assess the associated risk factors in both
      groups. A cross-sectional study was conducted at our hemodialysis unit from June
      to September 2009. A total of 180 patients and 180 caregivers were enrolled and
      the Beck's Depression Inventory (BDI-II) questionnaire was administered. Of the
      360 respondents, 201 (55.8%) were males and 264 (73.3) were married. According to
      the BDI scoring, 135 (75%) of the patients and 60 (33.4%) of the attendants were
      found to be moderately to severely depressed. Marriage (OR 1.817), low income
      status (OR 1.757) and unemployment (OR 4.176) correlated with increased
      depression grade, while gender and education level did not. Anemia was the only
      co-morbidity showing positive association with depression scores in the patients'
      group (P = 0.023). We conclude that the majority of the patients undergoing
      dialysis were depressed and were twice more likely to be depressed than their
      caregivers. In both groups, marriage and unemployment were associated with
      increased depressive symptoms, while household income showed negative association
      with depression. Gender and education level were not related to the depression
      scores.

PMID- 22982906
TI  - Assessment of quality of life in patients on hemodialysis and the impact of
      counseling.
AB  - Chronic renal failure is an irreversible progressive condition responsible for
      high morbidity and mortality. Because it requires life-long treatment in the form
      of renal replacement therapy, the quality of life (QOL) of patients may
      significantly impair. Studies have revealed that patient education can play a
      significant role in improving the QOL in these patients. The primary objective of
      this study was to assess the QOL of patients on hemodialysis by using the World
      Health Organization Quality of Life assessment scale and also to study the impact
      of patient counseling in these patients. Fifty patients were selected for the
      study and they were randomly divided into two groups, control and test;
      counseling was given to the test group of patients. There was an increase in
      score in all the four domains (physical, psychological, environmental and social)
      among the test group when compared with the control group. Also, we found that
      the psychological domain showed significant increase in score compared with
      others. Our findings demonstrate that patient counseling plays an important role
      in improving the QOL by changing their psychological thinking and bringing them
      toward spirituality.

PMID- 22982907
TI  - Perceived illness intrusions among continuous ambulatory peritoneal dialysis
      patients.
AB  - To study the perceived illness intrusion of continuous ambulatory peritoneal
      dialysis (CAPD) patients, to examine their demographics, and to find out the
      association among demographics, duration of illness as well as illness intrusion,
      40 chronic kidney disease stage V patients on CAPD during 2006-2007 were studied.
      Inclusion criteria were patients' above 18 years, willing, stable, and completed
      at least two months of dialysis. Those with psychiatric co-morbidity were
      excluded. Sociodemographics were collected using a semi-structured interview
      schedule. A 14-item illness intrusion checklist covering various aspects of life
      was administered. The subjects had to rate the illness intrusion in their daily
      life and the extent of intrusion. The data was analyzed using descriptive
      statistics and chi square test of association. The mean age of the subjects was
      56.05 +/- 10.05 years. There was near equal distribution of gender. 82.5% were
      married, 70.0% belonged to Hindu religion, 45.0% were pre-degree, 25.0% were
      employed, 37.5% were housewives and 30.0% had retired. 77.5% belonged to the
      upper socioeconomic strata, 95.0% were from an urban background and 65.0% were
      from nuclear families. The mean duration of dialysis was 19.0 +/- 16.49 months.
      Fifty-eight percent of the respondents were performing the dialysis exchanges by
      themselves. More than 95.0%were on three or four exchanges per day. All the 40
      subjects reported illness intrusion in their daily life. Intrusion was perceived
      to some extent in the following areas: health 47.5%, work 25.0%, finance 37.5%,
      diet 40.0%, and psychological 50.0%. Illness had not intruded in the areas of
      relationship with spouse 52.5%, sexual life 30.0%, with friends 92.5%, with
      family 85.5%, social functions 52.5%, and religious functions 75.0%.
      Statistically significant association was not noted between illness intrusion and
      other variables. CAPD patients perceived illness intrusion to some extent in
      their daily life. Elderly, educated married subjects were predominant. There was
      no statistically significant association between illness intrusion and other
      variables.

PMID- 22982908
TI  - Long-term outcome of the difficult nephrotic syndrome in children.
AB  - To determine the long-term outcome of nephrotic syndrome (NS) in children, we
      studied 48 patients with the NS aged seven months to 12 years at onset and
      followed for a long period (3-9 years). Consanguinity was positive in 31.2%.
      Patients' history of atopy was present in 25%, while family history of allergy
      was present in 18 (37.5%) patients. Renal impairment at initial presentation was
      observed in 12.5% of the patients. Among 32 biopsied patients, 11 (34.3%) had
      focal segmental glomerulosclerosis and eight (25%) revealed mesangial IgM
      nephropathy. Outcome at two years of presentation showed 41.6% patients as
      frequent relapsers, 39.5% as steroid dependent and 18.7% as steroid resistant.
      Forty-three patients were available for follow-up after ten years of
      presentation, 22 (51%) patients had complete remission, 15 (34.8%) were steroid
      dependent, two (4.6%) developed chronic renal failure and two (4.6%) died. Two
      patients (4.6%) developed insulin-dependent diabetes mellitus, two (4.6%) had
      cataract and one (2.3%) had documented peritonitis. In conclusion, the high
      incidence of steroid-dependent, frequent relapses and steroid resistance in
      children can be explained by different factors, including consanguinity, atopy
      and severe presentation at onset of disease. We suggest longer initial treatment
      at onset for this group of patients. The low incidence of infection in this group
      needs to be addressed in future studies.

PMID- 22982909
TI  - Rituximab in treatment of idiopathic glomerulopathy.
AB  - The aim of our study was to assess the role of rituximab (Mabthera) in the
      treatment of patients with corticosteroid-resistant and calcineurin-inhibitors +/
      cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients
      who had required the previous treatment for a minimum of two years were included
      in the study. Our protocol included the use of rituximab in four-weekly slow
      infusions. Five patients were excluded as they could not tolerate rituximab
      infusion for allergic reaction. As expected, none of the patients had a decline
      in the total circulating lymphocyte counts yet all had achieved decline of their
      initially normal CD20 to < 0.5% one month after infusion. The decline persisted
      for eight to ten months later. In the minimal change disease (MCD) group, 31 of
      the 32 patients had complete remission (CR) and were off any immunosuppressive
      therapy and one of the previous non-responders (NR) did not respond. Excluding
      two patients who had required retreatment, the others remained in CR (17 up to 28
      months and six up to 36 months). Treatment with rituximab resulted in
      amelioration of NS in 17 of the 18 patients with focal segmental
      glomerulosclerosis (FSGS), while only one patient remained NR. Although renal
      function remained stable, proteinuria reappeared by eight to 12 months.
      Retreatment with rituximab resulted in a similar response with stable kidney
      function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved
      CR. Two patients failed to respond and two had partial remission. By 12 months,
      all patients relapsed. The response was within one month following treatment in
      patient with MCD, but was gradual within three months in FSGS and MG. Relapsers
      in all groups responded in a similar pattern to repeat dosing with the drug
      subsequently. Our prospective study represents an adequate number of patients
      with biopsy-proven subgroups of INS in both children and adults with long-term
      follow-up of treatment with rituximab. The drug is effective and safe for
      treatment of patients refractory to the conventional agents.

PMID- 22982910
TI  - The clinical spectrum of idiopathic hyperuricosuria in children: isolated and
      associated with hypercalciuria/hyperoxaluria.
AB  - The clinical manifestations of hyperuricosuria (HU) are usually underestimated by
      the clinician. The aim of this study was to review the clinical spectrum of
      symptomatology of HU and to evaluate the presence of associated hypercalciuria
      (HC) and hyperoxaluria (HX). A retrospective review was done on 64 children with
      HU seen between January 2004 and December 2008. The patients were divided into HU
      19, HU + HC 4, HU + HX 21 and HU + HC + HX 20. The mean age at diagnosis was 80
      months (range six to 156 months). Duration of follow-up ranged was from six to 66
      months. There were 228 symptomatic episodes for 64 patients (males 31, females
      33). The relationship of symptomatology to age and gender were not significant.
      The most common symptoms were abdominal pain 67.2% (in 7/44 it was localized to
      the right lower quadrant, mimicking appendicitis), flank pain 59.4%, increased
      urinary frequency 43.4%, urgency 39%, enuresis 31.25%, oliguria 29.7%, dysuria
      25%, red urine 20.35%, vaginal itching 15.21%, dribbling 14.06%, orange urine
      12.5%, hesitancy 12.5% and penile pain 7.81%. To our knowledge, the vaginal
      itching and penile pain were not previously described. Family history was
      positive for stones and/or gout in 62.5%. The presence of a positive family
      history and red urine were significant (P-value <0.05) for the presence of an
      underlying HU. In the presence of recurrent abdominal/flank pain, hematuria
      without proteinuria or edema and urological symptomatology, especially in the
      presence of red urine, and a positive family history of gout or stones, a search
      for HU is in order. This will avoid unnecessary and invasive investigations.

PMID- 22982911
TI  - Value of renal resistive index as an early marker of diabetic nephropathy in
      children with type-1 diabetes mellitus.
AB  - Constant increase in the incidence of type-1 diabetes (T1-DM) has made it
      necessary to have new markers for the early detection of diabetic nephropathy
      (DN). One of the markers that could be helpful in detecting functional
      alterations in renal hemodynamics is assessment of the renal resistive index (RI)
      by using renal Doppler. We studied 25 patients with T1-DM (Group-A), which
      comprised of 15 females and 10 males, with a mean age of 10.8 +/- 2.2 years and
      duration of diabetes of 5 +/- 1.1 years. A control group (Group-B) comprising 20
      healthy children, 12 females and eight males with mean age of 11.6 +/- 2 years,
      was also studied. The following parameters were studied in the two groups: age,
      serum creatinine, albumin excretion rate (AER), glomerular filtration rate (GFR),
      glycosylated hemoglobin (HbA1c) and mean renal RI of both kidneys. We found an
      increase in the mean RI in diabetic patients versus healthy children; the mean RI
      in Group-A was 0.64 +/- 0.55 while it was 0.58 +/- 0.0.28 in Group-B (P <0.000).
      This increase in RI had a positive correlation with duration of the disease, GFR
      and HbA1c levels, but there was no correlation with serum creatinine or AER. We
      conclude that RI is increased early in TI-DM, and it can be a predictor of DN.

PMID- 22982912
TI  - Expression of angiotensin-converting enzyme mRNA gene in the kidneys of patients
      with glomerulonephrites.
AB  - A little is known about the behavior of the renin-angiotensin system (RAS) in
      glomerulo-nephritis (GN), although it is activated in other models of injury. To
      study renal angiotensin-converting enzyme (ACE) messenger ribonucleic acid (mRNA)
      gene expression in patients with GN to determine its role in the disease process
      and other factors that may influence the course of the disease and the prognosis,
      e.g. treatment with ACE inhibitor (ACEI) drugs, we studied 20 patients with GN
      allocated to two groups: ten patients received an ACEI drug and ten patients did
      not receive ACEI in addition to a control group of ten healthy subjects. Routine
      and special laboratory investigation, histopathological studies and quantitative
      polymerase chain reaction analysis for renal ACE mRNA were done for both the
      study and the control groups. There was a statistically significant increase in
      ACE mRNA gene expression in the GN groups than in control group, but no
      statistically significant difference in ACE mRNA gene expression between the
      patients group that received and the group that did not receive ACEI. A
      significant correlation was found between the ACE mRNA gene expression and the
      mean blood pressure, serum creatinine, blood urea nitrogen and 24-h urinary
      protein. In conclusion, a higher level of ACE mRNA gene expression in patients
      suffering from GN may suggest a role of the RAS in the process of GN, perhaps
      contributing to glomerular hypertrophy and matrix overproduction. The use of ACEI
      drugs possibly slows the rate of progression of renal failure and plays a role in
      controlling the pathophysiology.

PMID- 22982913
TI  - Non-diabetic renal disease in patients with type-2 diabetes mellitus.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in
      diabetics worldwide, yet most patients with type-2 diabetes mellitus are not
      formally evaluated with a renal biopsy. The diagnosis is almost always based on
      clinical grounds. A wide spectrum of non-diabetic renal disease (NDRD) is
      reported to occur in patients with type-2 diabetes. It has been estimated that up
      to one-third of all diabetic patients who present with proteinuria are suffering
      from NDRD. The aim of this analysis was to evaluate the prevalence and etiology
      of NDRD in patients with type-2 diabetes. We retrospectively reviewed the medical
      records of patients with type-2 diabetes who underwent kidney biopsy on clinical
      suspicion of NDRD (absence of diabetic retinopathy and/or neuropathy; short
      duration of diabetes, i.e. less than five years) from January 2003 through
      December 2007 at the Aga Khan University Hospital, Karachi. Based on the biopsy
      findings, patients were grouped as Group-I, isolated NDRD; Group-II, NDRD with
      underlying DN; and Group-III, isolated DN. Of 68 patients studied, 75% were males
      and the mean age was 56 years. The mean duration of diabetes was nine years.
      Group-I included 34 patients (52%), Group-II included 11 patients (17%) and Group
      III included 23 patients (31%). Among the Group-I patients, the mean age was 56
      years (41-77 years). The most common NDRDs were acute interstitial nephritis
      (32%), diffuse proliferative glomerulonephritis (17%); membranous nephropathy
      (12%) and crescentic glomerulonephritis (12%). Among Group-II, the mean age was
      60 years (46-71 years), and the most common lesion was interstitial nephritis
      superimposed on underlying DN (63% cases). Among Group-III, the mean age was 53
      years (42- 80 years). The mean proteinuria was 5, 6.3 and 7.3 g/24 h of urine
      collection in Groups I, II and III, respectively (P = NS). The mean duration of
      diabetes was 7.3, 11.7 and 10.7 years in Groups I, II and III, respectively. The
      duration of diabetes was significantly less in Group-I compared with Group-II and
      Group-III (P = 0.04). Our study suggests that the prevalence of NDRD (either
      isolated or superimposed on underlying DN) is high in appropriate clinical
      settings. Performing renal biopsy in diabetics with no extrarenal end organ
      damage other than nephropathy helps to diagnose and treat NDRD. This is the first
      report from Pakistan documenting the prevalence of NDRD in patients with type-2
      diabetes.

PMID- 22982914
TI  - Histomorphological classification of focal segmental glomerulosclerosis: a
      critical evaluation of clinical, histologic and morphometric features.
AB  - Primary focal segmental glomerulosclerosis (FSGS) has recently been divided into
      five subtypes by the Columbia classification. However, little is known about the
      incidence of these subtypes in the Indian population. In addition, there are very
      few studies evaluating the clinico-pathologic features with morphometric
      parameters in these subtypes. This study was aimed at evaluating the clinical,
      histopathological and morphometric parameters in various subtypes of FSGS at our
      referral center. Sixty-five (65) cases of idiopathic FSGS, diagnosed over two
      years (2006-2007), were included in the study. Detailed clinical and biochemical
      investigations were noted. Histological sections were reviewed and cases
      classified according to the Columbia classification and various glomerular and
      tubulo-interstitial features were noted. Glomerular morphometry on digitized
      images was performed using image analysis software. Renal biopsies with minimal
      change disease were used as controls for morphometric evaluation. In this study,
      FSGS not otherwise specified (NOS) was the most common subtype (44.6%), followed
      by perihilar FSGS (24.6%), collapsing (13.8%), tip (12.3%) and cellular FSGS
      (4.6%). Collapsing subtype showed significantly shorter duration of symptoms and
      higher degree of proteinuria, mean serum urea and creatinine compared with the
      other subtypes. On histologic analysis, features like glomerular hyalinosis,
      capsular adhesion, mesangial proliferation and visceral epithelial cell
      prominence (VEP) were frequently seen. The cases with VEP had a shorter duration
      of symptoms and a higher mean serum creatinine and 24-h urine protein excretion
      compared with those without VEP. The morphometric study revealed a significant
      higher mean glomerular area in the NOS, perihilar and collapsing variants as
      compared with the control biopsies. The present study highlights the differences
      in the prevalence in the FSGS subtypes in our population compared with the
      western data. Also, the significant differences in the clinical, biochemical and
      histological parameters reaffirm the utility of the Columbia classification of
      FSGS in routine reporting of renal biopsies. We found VEP (without causing
      collapse of the tuft) to be associated with higher serum creatinine at
      presentation. This feature needs to be evaluated in further studies for its
      potential significance.

PMID- 22982915
TI  - Tuberculosis of the arterio-venous graft in a renal transplant recipient.
AB  - A 44-year-old Pakistani lady with end-stage renal disease secondary to rapidly
      proliferative glomerulonephritis underwent successful renal transplantation.
      Three years later, she was referred to the surgeon with an abscess in the
      axillary region at the site of a previous arterio-venous (AV) graft. She
      underwent repeated incision and drainage of the abscess, which was constantly
      recurring. Nine months later, she presented with a tender swelling at the site of
      the AV graft with purulent discharge. The graft was removed; culture and
      histology confirmed the presence of tuberculosis (TB). This patient presents a
      rare case of TB infection in the AV graft.

PMID- 22982916
TI  - Severe pneumococcal hemolytic uremic syndrome in an 8-month-old girl.
AB  - The hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic
      anemia, thrombocytopenia and acute renal failure, represents one of the major
      causes of acute renal failure in infancy and childhood. The typical form
      occurring after an episode of diarrhea caused by Escherichia coli is the most
      frequent in children. Other microorganisms also may be responsible for HUS, such
      as Streptococcus pneumoniae, which causes more severe forms of the disease. We
      report an 8-month-old girl who presented with pneumonia and subsequently
      developed HUS. Renal biopsy showed characteristic lesion of thrombotic
      microangiopathy and extensive cortical necrosis. She was managed with peritoneal
      dialysis but did not improve and developed severe sepsis due to staphylococcal
      peritonitis, resulting in the death of the patient. Streptococcus pneumoniae
      induced HUS is uncommon, but results in severe disease in the young. There is a
      high risk of these patients developing end-stage kidney disease in the long term.

PMID- 22982917
TI  - Severe upper extremity polyneuropathy due to inferior brachial plexus compression
      as a result of left subclavian artery pseudoaneurysm.
AB  - In the present report, we describe the case of a 76-year-old hemodialysis patient
      who was admitted with clinical features of neurological thoracic exit syndrome
      due to subclavian artery pseudoaneurysm following the insertion of a dual lumen
      vascular internal jugular catheter (vascath) with excellent outcome after endo
      arterial stent placement.

PMID- 22982918
TI  - PEComa of the urinary bladder.
AB  - Perivascular epithelioid cell tumors are a family of related mesenchymal
      neoplasms that include angiomyolipoma, lymphangiomyomatosis, clear cell sugar
      tumor of the lung and a group of rare morphologically and immunophenotypically
      similar lesions that show immunoreactivity for both melanocytic (HMB-45 and/or
      melan-A) and smooth muscle (actin and/or desmin) markers. This case is presented
      for its rare occurrence and characteristic morphologic and immunohistochemical
      features.

PMID- 22982919
TI  - Distal renal tubular acidosis in a child with HIV infection.
AB  - Renal tubular acidosis (RTA) is not uncommon in HIV-infected children with
      advanced disease, and has been described mainly due to nephrotoxic anti
      retroviral therapy and in association with prophylaxis or treatment of
      Pneumocystis carinii pneumonia with co-trimoxazole. We describe an 8-year-old
      boy, newly diagnosed to have HIV infection, who presented with distal RTA. There
      were no features of chronic RTA in the form of rickets or nephrocalcinosis,
      making an inherited form unlikely.

PMID- 22982920
TI  - Resolving basal ganglia calcification in hereditary hypomagnesemia with secondary
      hypocalcemia due to a novel TRPM6 gene mutation.
AB  - Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare condition
      caused by mutations in the transient receptor potential melastatin 6 (TRPM6)
      gene. Patients usually present during early infancy with symptomatic
      hypocalcemia; however, intracranial calcification has not been previously
      reported in HSH. We report on a three-month-old Saudi girl who presented with
      hypocalcemic convulsions and was initially treated as nutritional rickets.
      However, further biochemical analysis of blood and urine were suggestive of HSH.
      This diagnosis was confirmed by mutation analysis, which identified a novel
      homozygous frame shift mutation (ins 2999T) of the TRPM6 gene. A computed
      tomography brain scan, done around the time of diagnosis, identified bilateral
      basal ganglia calcification (BGC). Her serum calcium and the BGC improved with
      magnesium replacement. BGC can be added as a new feature of HSH and the case
      highlights the importance of measuring serum Mg in patients with hypocalcemic
      convulsions, particularly in children of consanguineous parents.

PMID- 22982921
TI  - Forgotten long-term indwelling double "J" stent.
AB  - A poor, uneducated patient from a rural background presented to us with burning
      micturition and colicky pain in the loin. He had undergone surgery for pelvi
      ureteric junction (PUJ) obstruction on the right side four years earlier.
      Following surgery, the patient was irregular in his follow-up and, as such, he
      did not get the double "J" (DJ) stent, which was placed during surgery, removed.
      Ultrasonography performed during the present admission revealed mild
      hydronephrosis of the right kidney with a tiny calculus in the urinary bladder.
      Intravenous urography revealed mild hydronephrosis with the DJ stent in situ in
      the right kidney. After an unsuccessful attempt with cystoscopy, the stent was
      removed successfully by suprapubic cystostomy. The post-operative course was
      uneventful and the patient was discharged in seven days.

PMID- 22982922
TI  - Emphysematous pyelonephritis in a patient infected with the human
      immunodeficiency virus.
AB  - Emphysematous pyelonephritis (EPN) is a rapidly progressive and life-threatening
      infection that is seen most commonly in persons with diabetes. The infecting
      organisms usually consist of mixed flora, including Escherichia coli (68%),
      Klebsiella pneumoniae (9%) and Proteus mirabilis. Females are affected twice as
      often as men, and mortality rates can be as high as 80%. Obstructive uropathy,
      urinary calculi, calyceal stenosis and neoplasms are significant predisposing
      factors. We report a case of EPN in a patient with the human immunodeficiency
      virus infection, without diabetes mellitus or urinary tract obstruction, which
      responded remarkably to conservative management with antibiotics alone.

PMID- 22982923
TI  - Importance and process of feedback in undergraduate medical education in Saudi
      Arabia.
AB  - Feedback is an essential element in the process of students' learning and
      development. This study aimed to explore the views of medical students regarding
      the importance and process of feedback in their medical education. A cross
      sectional questionnaire-based study was conducted in our college of medicine. The
      questionnaire included questions to assess the students' views about the
      importance and the need of feedback in the learning process and whether feed-back
      should follow certain or all forms of assessment. In addition, the questionnaire
      contained questions that aimed to explore students' views about the contents and
      process of feedback. One hundred and eighty-six male medical students
      participated in this study. While the majority of students (85%) indicated that
      feedback was important for their learning and expressed their need for regular
      feedback during their study, only about 20% of them indicated receiving regular
      feed-back. Senior students perceived that they received feedback less frequently
      than their junior colleagues' (P <0.05). The majority of the participants
      expressed their interest into receiving an immediate feedback after their
      summative and formative assessment. Students think that feedback should be
      balanced and include a suggested plan for their future learning process. Senior
      students showed a higher preference to have feedback that also contained points
      related to their strengths more than juniors. Students also indicated their
      preference to have one-to-one and written feed-back more than feedback that was
      conveyed in groups and verbally. These issues are of high importance and should
      be considered for planning and implementing an effective feedback system.

PMID- 22982924
TI  - Hepatitis C virus core antigen testing in the monitoring of patients on dialysis.

PMID- 22982925
TI  - Unrecognized migration of an entire guide wire during hemodialysis catheter
      placement.

PMID- 22982926
TI  - Peritonitis in patients on peritoneal dialysis: a single-center experience from
      Dakar.

PMID- 22982927
TI  - The change in the spectrum of glomerulonephritis in Egypt over the past decade.

PMID- 22982928
TI  - Urinary tumor marker in bladder carcinoma in Upper Egypt, correlations with
      different clinicopathological features.

PMID- 22982929
TI  - Complement evaluation in atypical hemolytic uremic syndrome: current concepts.

PMID- 22982930
TI  - Renal transplantation with B cell-positive crossmatch.

PMID- 22982931
TI  - Metabolic syndrome in chronic renal failure.

PMID- 22982932
TI  - Spectrum of biopsy-proven glomerular disease in Al Qassim region: a single centre
      experience.

PMID- 22982933
TI  - Hematuria and renal involvement at presentation in acute lymphoblastic leukemia.

PMID- 22982935
TI  - Malaria incidence among kidney-transplanted recipients in an endemic malaria
      area, Sudan.
AB  - Malaria is endemic all over Sudan. The population are at risk of malaria
      infection to variable degrees. Kidney-transplanted patients on maintenance
      immunosuppressive therapy are known to be prone to infection, but there is not
      enough data in the medical literature as to whether they are more susceptible to
      malaria infection in endemic areas. This study was conducted in the Gezira
      Hospital for Renal Diseases and Surgery to assess the effect of maintenance
      immunosuppressive therapy in renal transplantation on malaria incidence. A total
      of 110 individuals were enrolled: 55 were renal-transplanted patients with end
      stage renal disease who received kidney transplantation at least one year earlier
      and were on maintenance immunosuppressive medications. The other 55 individuals
      were the compatible healthy group. Thorough follow-up was exercised for both
      groups for one year (January-December 2009). Following the World Health
      Organization criteria for malaria diagnosis, a total of 51 malarial attacks were
      reported in both the groups, 25 in the transplanted group and 26 in the controls.
      The incidence difference between both groups was statistically insignificant
      [0.76 (+/- 1.170) and 1.09 (+/- 1.917) P = 0.282 among transplanted group and
      control group, respectively]. Providing routine malaria prophylaxis is not
      required for renal transplant recipients on maintenance immunosuppressive.

PMID- 22982934
TI  - Clinical characterization and NPHP1 mutations in nephronophthisis and associated
      ciliopathies: a single center experience.
AB  - Nephronophthisis (NPHP) is a recessive disorder of the kidney that is the leading
      genetic cause of end-stage renal failure in children. Egypt is a country with a
      high rate of consanguineous marriages; yet, only a few studies have investigated
      the clinical and molecular characteristics of NPHP and related ciliopathies in
      the Egyptian population. We studied 20 children, from 17 independent families,
      fulfilling the clinical and the ultrasonographic criteria of NPHP. Analysis for a
      homozygous deletion of the NPHP1 gene was performed by polymerase chain reaction
      on the genomic DNA of all patients. Patients were best categorized as 75%
      juvenile NPHP, 5% infantile NPHP, and 20% Joubert syndrome-related disorders
      (JSRD). The mean age at diagnosis was 87.5 + 45.4 months, which was significantly
      late as compared with the age at onset of symptoms, 43.8 +/- 29.7 months (P
      <0.01). Homozygous NPHP1 deletions were detected in six patients from five of 17
      (29.4%) studied families. Our study demonstrates the clinical phenotype of NPHP
      and related disorders in Egyptian children. Also, we report that homozygous NPHP1
      deletions account for 29.4% of NPHP in the studied families in this cohort,
      thereby confirming the diagnosis of type-1 NPHP. Moreover, our findings confirm
      that NPHP1 deletions can indeed be responsible for JSRD.

PMID- 22982936
TI  - Post-transplantation diabetes mellitus.
AB  - To determine the prevalence of post-kidney transplantation diabetes (PTDM) and to
      assess its risk factors, we retrospectively studied 92 non-diabetic kidney
      transplant patients. The immunosuppressive drugs used to prevent rejection
      included prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus) and an
      antimetabolite (azathioprine or mycofenolate mofetil). Diabetes was defined
      according to the WHO criteria and the American Diabetes Association. The mean age
      of our patients was 35.8 +/- 10.5 years, and there was a clear male predominance
      (56 men and 36 women). The graft was from living related donor in 71/92 (76%)
      patients. The prevalence of diabetes in post-kidney transplant was 15.2%. The
      factors increasing the occurrence of PTDM included advanced age, high doses of
      steroids and cyclosporine. Management of PTDM included diet modification, oral
      anti-diabetic and insulin. We conclude that the prevalence of PTDM is significant
      in our transplant population and risk factors for its development are multiple
      and require aggressive multifaceted management.

PMID- 22982937
TI  - A retrospective review of diabetic nephropathy patients during referral to the
      sub-urban nephrology clinic.
AB  - Diabetic nephropathy (DN) has become the most common cause of end-stage renal
      failure. Early referral and specific nephrology treatment could delay the disease
      progression and should reduce the treatment cost, mortality and morbidity rate in
      these patients. This is a single-center, retrospective review of all DN patients
      referred to the nephrology clinic in Hospital Sultan Ahmad Shah, Temerloh, from
      2000 to 2009, to study and define the clinical characteristics of DN patients at
      the time of the referral to the nephrology clinic. A total of 75 patient case
      records were reviewed. Forty-three (57.3%) of them were males, with a median age
      of 64.3 +/- 8.5 years at the time of referral. Only 14.7% of them had blood
      pressure lower than 125/75 mmHg. Co-morbid and disease-related complications were
      also commonly diagnosed and 28.4% (n = 21) had ischemic heart disease, 23% (n =
      17) had diabetic retinopathy and 20.3% (n = 15) had diabetic neuropathy. The mean
      serum creatinine at the time of referral was 339.8 +/- 2.3 MUmol/L, gylcated
      hemoglobin A 1c (HbA1C) was 8.1 +/- 2.0 %, serum fasting glucose was 9.6 +/- 4.7
      mmol/L, serum cholesterol was 5.4 +/- 1.2 mmol/L and hemoglobin level was 10.6 +/
      2.9 g/dL. Although female patients were less frequently seen in the early stages
      of chronic kidney disease (CKD), they comprised at least 72.7% of CKD stage 5
      (male:female; 6:16, P <0.05). Twenty-nine percent (n=22) of them were referred at
      CKD stage 5, 48% (n=36) were at CKD stage 4, 17.3% (n=13) were at CKD stage 3, 4%
      (n=3) were at CKD stage 2 and 1.3% (n=1) was at CKD stage 1. Advanced CKD
      patients were frequently prescribed with more antihypertensives. CKD stage 5
      patients were prescribed with two-and-half types of antihypertensive as compared
      to two types of anti-hypertensive in CKD stage 2 and stage 3. Furthermore, ACE
      inhibitors (ACE-I) were less frequently prescribed to them. Only 22.7% (n=5) of
      CKD stage 5 patients received ACE-I and 30% (n=11) in CKD stage 4 patients as
      compared to 53.4% (n=7) in CKD patients stage 3. This review shows that DN
      patients were referred late to the nephrologists and the overall disease
      management was suboptimal. Antihypertensive requirement was also increased and
      ACEIs were less frequently prescribed in the advanced diabetic nephropathy
      patients.

PMID- 22982938
TI  - Analytical and computational modeling of fluctuation electron microscopy from a
      nanocrystal/amorphous composite.
AB  - A nanocrystal/amorphous composite is an idealized model of the medium-range order
      structure in a variety of amorphous materials. We have investigated the
      fluctuation electron microscopy (FEM) signal from such a model analytically and
      with computer simulations. In the analytical modeling, we improved the previous
      model by Stratton and Voyles (Ultramicroscopy 108, 727 (2008)) by introducing the
      partial occupancy of nanocrystals in a column, the effect of the deviation
      parameter on the diffracted intensity, and a distribution of nanocrystal sizes.
      The improved model no longer has a maximum in the FEM signal as a function of the
      volume fraction of nanocrystals. In the computer modeling, we compared the
      variance calculated using kinematic scattering and dynamical scattering and
      investigated the effects of disorder and strain inside the nanocrystals on the
      variance. The variance based on dynamical scattering is about 15% smaller than
      that based on kinematic scattering. Disorder introduced in the nanocrystal
      reduces the variance peaks at all scattering vectors, with a much larger
      reduction at longer scattering vector.

PMID- 22982939
TI  - Biomagnification of mercury through lake trout (Salvelinus namaycush) food webs
      of lakes with different physical, chemical and biological characteristics.
AB  - Mercury (Hg) biomagnification in aquatic ecosystems remains a concern because
      this pollutant is known to affect the health of fish-eating wildlife and humans,
      and the fish themselves. The "rate" of mercury biomagnification is being assessed
      more frequently using stable nitrogen isotope ratios (delta(15)N), a measure of
      relative trophic position of biota within a food web. Within food webs and across
      diverse systems, log-transformed Hg concentrations are significantly and
      positively related to delta(15)N and the slopes of these models vary from one
      study to another for reasons that are not yet understood. Here we compared the
      rates of Hg biomagnification in 14 lake trout lakes from three provinces in
      Canada to understand whether any characteristics of the ecosystems explained this
      among-system variability. Several fish species, zooplankton and benthic
      invertebrates were collected from these lakes and analyzed for total Hg (fish
      only), methyl Hg (invertebrates) and stable isotopes (delta(15)N; delta(13)C to
      assess energy sources). Mercury biomagnification rates varied significantly
      across systems and were higher for food webs of larger (surface area), higher
      nutrient lakes. However, the slopes were not predictive of among-lake differences
      in Hg in the lake trout. Results indicate that among-system differences in the
      rates of Hg biomagnification seen in the literature may be due, in part, to
      differences in ecosystem characteristics although the mechanisms for this
      variability are not yet understood.

PMID- 22982940
TI  - Effects of over-winter green cover on groundwater nitrate and dissolved organic
      carbon concentrations beneath tillage land.
AB  - Application of over-winter green cover (e.g. cover crops) as a measure for
      reducing nitrate losses from tillage land has been frequently investigated,
      especially in the unsaturated zone. Monitoring of groundwater is less common in
      these studies. Studies on groundwater responses to different land treatments can
      be challenging because they can be influenced by various conditions, such as
      recharge, seasonal variations, and aquifer properties, often occurring at
      different time scales than surface water processes. The aim of this study was to
      evaluate groundwater nitrate (NO(3)(-)N) and dissolved organic carbon (DOC)
      concentration responses to different over-winter green covers: mustard, natural
      regeneration and no cover. A field experiment was designed and run for three
      years on tillage land underlain by a vulnerable sand and gravel aquifer in the
      south-east of Ireland. Results showed that over-winter green cover growth on
      tillage land can be an effective measure to reduce groundwater NO(3)(-)N
      concentrations. A significant decrease in groundwater NO(3)(-)N concentrations
      was observed under the mustard cover compared to no cover. All treatments,
      including no cover, showed a decline in groundwater NO(3)(-)N concentrations over
      time. A significant increase in groundwater DOC was also observed under the
      mustard cover. Although the overall groundwater DOC concentrations were low, the
      increased DOC occurrence in groundwater should be accounted for in carbon
      balances and could potentially enhance groundwater denitrification in cases where
      aquifer conditions may favour it.

PMID- 22982941
TI  - Post-stimulation effect of electroacupuncture at Yintang (EX-HN3) and GV20 on
      cerebral functional regions in healthy volunteers: a resting functional MRI
      study.
AB  - Objective The aim of the present work was to observe the activation/deactivation
      of cerebral functional regions after electroacupuncture (EA) at Yintang (EX-HN3)
      and GV20 by functional MRI (fMRI). Design A total of 12 healthy volunteers were
      stimulated by EA at Yintang and GV20 for 30 min. Resting-state fMRI scans were
      performed before EA, and at 5 and 15 min after needle removal. Statistical
      parametric mapping was used to preprocess initial data, and regional homogeneity
      (ReHo) and amplitude of low-frequency fluctuation (ALFF) were analysed. Results
      ReHo at 5 min post stimulation showed increases in the left temporal lobe and
      cerebellum and decreases in the left parietal lobe, occipital lobe and right
      precuneus. At 15 min post stimulation, ReHo showed increases in the left fusiform
      gyrus; lingual gyrus; middle temporal gyrus; postcentral gyrus; limbic lobe;
      cingulate gyrus; paracentral lobule; cerebellum, posterior lobe, declive; right
      cuneus and cerebellum, anterior lobe, culmen. It also showed decreases in the
      left frontal lobe, parietal lobe, right temporal lobe, frontal lobe, parietal
      lobe and right cingulate gyrus. ALFF at 5 min post stimulation showed increases
      in the right temporal lobe, but decreases in the right limbic lobe and posterior
      cingulate gyrus. At 15 min post stimulation ALFF showed increases in the left
      frontal lobe, parietal lobe, occipital lobe, right temporal lobe, parietal lobe,
      occipital lobe and cerebellum, but decreases in the left frontal lobe, anterior
      cingulate gyrus, right frontal lobe and posterior cingulate gyrus. Conclusions
      After EA stimulation at Yintang and GV20, which are associated with psychiatric
      disorder treatments, changes were localised in the frontal lobe, cingulate gyrus
      and cerebellum. Changes were higher in number and intensity at 15 min than at 5
      min after needle removal, demonstrating lasting and strong after-effects of EA on
      cerebral functional regions.

PMID- 22982942
TI  - Rho GTPases in pulmonary vascular dysfunction.
AB  - Rho proteins, best known for their regulatory role in actin dynamics, stimulate a
      variety of processes important in the control of vascular function, including
      morphogenesis, migration, cell proliferation and adhesion, cell survival, gene
      expression, vesicle transport and microparticle formation. Rho GTPases have been
      implicated in several pulmonary vascular pathologies. Here we give an overview of
      the current knowledge of the role of Rho GTPases in vascular dysfunction, and
      pulmonary diseases such as pulmonary hypertension, pulmonary embolism, chronic
      obstructive pulmonary disease, acute lung injury and acute respiratory distress
      syndrome.

PMID- 22982943
TI  - Sterile inflammation in the liver.
AB  - Inflammation In the absence of pathogens occurs in all tissues in response to a
      wide range of stimuli that cause tissue stress and injury. Such sterile
      inflammation (SI) is a key process in drug-induced liver injury, nonalcoholic
      steatohepatitis, and alcoholic steatohepatitis and is a major determinant of
      fibrosis and carcinogenesis. In SI, endogenous damage-associated molecular
      patterns (DAMPS), which are usually hidden from the extracellular environment,
      are released on tissue injury and activate receptors on immune cells. More than
      20 such DAMPS have been identified and activate cellular pattern recognition
      receptors, which were originally identified as sensors of pathogen-associated
      molecular patterns. Activation of pattern recognition receptors by DAMPS results
      in a wide range of immune responses, including production of proinflammatory
      cytokines and localization of immune cells to the site of injury. DAMPS result in
      the assembly of a cytosolic protein complex termed the inflammasome, which
      activates the serine protease caspase-1, resulting in activation and secretion of
      interleukin-1beta and other cytokines. SI-driven liver diseases are responsible
      for the majority of liver pathology in industrially developed countries and lack
      specific therapy. Identification of DAMPS, their receptors, signaling pathways,
      and cytokines now provides a wide range of therapeutic targets for which many
      antagonists are already available.

PMID- 22982944
TI  - Effect of natural cross-linkers incorporation in a self-etching primer on dentine
      bond strength.
AB  - OBJECTIVES: The aim of this in vitro study was to investigate the effect of
      incorporation of natural cross-linkers into the primer of a self-etching adhesive
      on resin-dentine bond strength. METHODS: Flat dentine surfaces were prepared from
      extracted human molar teeth and were applied with the following self-etching
      primers. The 0.5% hesperidin (HPN), 0.5% chlorhexidine (CHX) or 0.5% grape seed
      extract (GSE) was incorporated into Clearfil SE primer (Kuraray Medical, Inc.) to
      formulate three experimental primers. The original SE primer served as control.
      Following primer application, the teeth were bonded with Clearfil SE bond,
      restored with resin composite and stored in water for 24 h at 37  degrees C. The
      bonded specimens were sectioned into beams and subjected to micro tensile bond
      testing (MUTBS). Failure analysis and morphological evaluation of the dentine
      surfaces were performed using a scanning electron microscope (SEM). Hardness (H)
      and elastic modulus (EM) were measured using nano-indentation technique to
      examine the mechanical properties of the bonded interfaces. RESULTS: One-way
      ANOVA showed significant differences in MUTBS, H and EM among the tested and
      control groups (p < 0.001). Tukey post hoc test revealed that incorporation of
      HPN significantly increased MUTBS, H and EM, when compared with the other groups
      (p < 0.006). The GSE-incorporated group significantly decreased MUTBS, H and EM,
      when compared with the other groups (p < 0.006); while CHX-incorporated group did
      not show any statistical significant difference when compared with the control
      group. CONCLUSION: Incorporation of HPN into Clearfil SE primer had a positive
      influence on the immediate MUTBS and mechanical properties of the bonded
      interface.

PMID- 22982945
TI  - The impact of inflammation to the antioxidant defense parameters in AMD patients.
AB  - BACKGROUND AND AIMS: Oxidative stress and inflammation are postulated to be
      involved in the pathogenesis of the age-related macular degeneration (AMD)
      although the mechanism linking the oxidation and inflammation is still unknown.
      The aim of this study was the analysis of the antioxidant capacity measured by
      levels of the antioxidant enzymes: superoxide dismutase (SOD), glutathione
      peroxidase (GPx), glutathione reductase (GR) and total antioxidant status (TAS)
      along with the inflammatory markers such as Creactive protein (CRP), interleukin
      6 (IL-6) and fibrinogen in AMD patients in order to analyze the relationship of
      the inflammatory markers with the antioxidant parameters and their association
      with AMD. METHODS: The cross-sectional study, carried out in the University
      clinical setting, included 84 patients with the age-related macular degeneration,
      aged 71.25+/-7.14 years and 84 aged-matched control subjects (CG). RESULTS:
      Statistical analysis revealed significantly lower GR (p=0.007) and TAS (p<0.000)
      values in the group of AMD patients compared to the controls. Logistic regression
      analysis showed that higher values of inflammatory markers (CRP>3 mg/L, IL>4.9
      pg/mL, fibrinogen>3.8 g/L) and lower values of antioxidative parameters (SOD<900
      U/gHb, GR<55 U/L and TAS<1.15 mmol/L) were significantly associated with AMD
      (ORCRP: 1.29, 95% CI 0.54-3.12, p<0.05; ORIL-6: 3.53, 95% CI 1.16-10.75, p=0.024;
      ORFIB: 3.06, 95% CI 1.78-7.92, p=0.019; ORSOD: 2.39, 95% CI 0.78-7.35, p<0.05;
      ORGR: 4.04, 95% CI 1.28-12.73, p=0.013; ORTAS: 2.9, 95% CI 1.4- 6.3, p=0.032).
      CONCLUSIONS: Based on the results obtained, it may be concluded that the
      antioxidant defense system was significantly reduced in patients with AMD and the
      probability to develop AMD was higher in older individuals with lower values of
      antioxidant parameters and higher values of inflammatory markers.

PMID- 22982946
TI  - Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure.
AB  - BACKGROUND: Esophageal achalasia is most commonly treated with laparoscopic
      myotomy or endoscopic dilation. Per-oral endoscopic myotomy (POEM), an
      incisionless selective myotomy, has been described as a less invasive surgical
      treatment. This study presents 6-month physiological and symptomatic outcomes
      after POEM for achalasia. METHODS: Data on single-institution POEMs were
      collected prospectively. Pre- and postoperative symptoms were quantified with
      Eckardt scores. Objective testing (manometry, endoscopy, timed-barium swallow)
      was performed preoperatively and 6 months postoperatively. At 6 months,
      gastroesophageal reflux was evaluated by 24-hour pH testing. Pre-/postmyotomy
      data were compared using paired nonparametric statistics. RESULTS: Eighteen
      achalasia patients underwent POEMs between October 2010 and October 2011. The
      mean age was 59 +/- 20 years and mean body mass index was 26 +/- 5 kg/m. Six
      patients had prior dilations or Botox injections. Myotomy length was 9 cm (7-12
      cm), and the median operating time was 135 minutes (90-260). There were 3
      intraoperative complications: 2 gastric mucosotomies and 1 full-thickness
      esophagotomy, all repaired endoscopically with no sequelae. The median hospital
      stay was 1 day and median return to normal activity was 3 days (3-9 days). All
      patients had relief of dysphagia [dysphagia score <= 1 ("rare")]. Only 2 patients
      had Eckardt scores greater than 1, due to persistent noncardiac chest pain. At a
      mean follow-up of 11.4 months, dysphagia relief persisted for all patients.
      Postoperative manometry and timed barium swallows showed significant improvements
      in lower esophageal relaxation characteristics and esophageal emptying,
      respectively. Objective evidence of gastroesophageal reflux was seen in 46%
      patients postoperatively. CONCLUSIONS: POEM is safe and effective. All patients
      had dysphagia relief, 83% having relief of noncardiac chest pain. There is
      significant though mild gastroesophageal reflux postoperatively in 46% of
      patients in 6-month pH studies. The lower esophageal sphincter shows normalized
      pressures and relaxation.

PMID- 22982947
TI  - Effectiveness of peer-led education on knowledge, attitude and risk behavior
      practices related to HIV among students at a Malaysian public university--a
      randomized controlled trial.
AB  - OBJECTIVE: Develop, implement and evaluate the effectiveness of a peer-led
      education program related to HIV/AIDS among university students. METHOD:  DESIGN:
      randomized controlled trial with 276 university students at Faculty of Medicine
      and Health Sciences University Putra Malaysia (UPM), Serdang in 2011.
      INTERVENTION: A peer-led education program on HIV prevention by university
      students. OUTCOME: differences in knowledge, attitude and risk behavior practices
      related to HIV between baselines, immediate follow-up after intervention and
      after three months. RESULTS: Significant improvement in sound knowledge in the
      intervention group as compared to the control group (Odds ratio, 1.75; 95% CI
      1.01, 3.00; p=0.04) and improvement in good attitude related to HIV (Odds ratio
      2.22; 95% CI 1.37, 3.61; p=0.01). The odds of high substance risk behavior was
      significantly reduced in the intervention group as compared to the control group
      (Odds ratio 0.07; 95% CI 0.02, 0.34; p=0.01). The association between good
      knowledge and intervention was modified by the different time points (baseline,
      immediately after intervention and 3 months after intervention), ethnicity and
      gender. CONCLUSION: Peer-led education program in HIV prevention improves
      knowledge, attitude and substance risk behavior. Changes in sexual risk behavior
      may require a longer follow-up.

PMID- 22982948
TI  - Take a walk in the park? A cross-over pilot trial comparing brisk walking in two
      different environments: park and urban.
AB  - OBJECTIVE: The objective of the present study is to investigate whether
      differences exist between a 30 minute brisk walk taken in two different
      environments in order to determine which environment best facilitates current
      physical activity guidelines: park or urban. METHODS: In this randomised cross
      over pilot study, participants performed a self-timed 30 minute brisk walk in two
      different environments, park and urban, in Glasgow, Scotland (October 2009 to
      January 2010). Cadence, recorded using the activPALTM activity monitor, was used
      to measure intensity. Outcome measures were: mean cadence; moderate-to-vigorous
      physical activity time accumulated in bouts lasting >= 10 min; number of walking
      breaks; and duration. RESULTS: A convenience sample of 40 healthy adults was
      recruited: 16 males, 24 females, mean age 22.9 (5.5) years. The mean cadence for
      the whole walk was higher in the park: 119.3 (8.3) vs. 110.9 (8.9) steps/min.
      Participants accumulated more moderate-to-vigorous physical activity in >= 10
      minute bouts during park walks: 25.5 (9.6) [median (interquartile range)] vs.
      14.0 (20.3) min. There was no difference in self-timed duration between
      locations. CONCLUSION: Participants accumulated more moderate-to-vigorous
      physical activity in bouts >= 10 min in duration on park walks due to the lack of
      interruptions in walking. Hence the park environment better facilitated the
      achievement of current physical activity guidelines. Further research involving a
      larger, more heterogeneous sample is recommended.

PMID- 22982950
TI  - 30th ESPID annual meeting in Thessaloniki, Greece: three decades of ESPID.

PMID- 22982951
TI  - A knee ulcer in a teenager with acute myeloid leukemia.

PMID- 22982952
TI  - Risk for invasive Kingella kingae infections and day-care facility attendance.

PMID- 22982953
TI  - Use of immature-to-total-neutrophil ratio in early neonatal sepsis.

PMID- 22982955
TI  - Reptile pets-associated Salmonella enterica subspecies diarizonae gastroenteritis
      in a neonate.

PMID- 22982956
TI  - High rates of ESBL-producing Escherichia coli in young children who traveled
      recently to India.

PMID- 22982958
TI  - Identifying the dynamic compressive stiffness of a prospective biomimetic
      elastomer by an inverse method.
AB  - Soft elastomeric materials that mimic real soft human tissues are sought to
      provide realistic experimental devices to simulate the human body's response to
      blast loading to aid the development of more effective protective equipment. The
      dynamic mechanical behavior of these materials is often measured using a Kolsky
      bar because it can achieve both the high strain rates (>100s(-1)) and the large
      strains (>20%) that prevail in blast scenarios. Obtaining valid results is
      challenging, however, due to poor dynamic equilibrium, friction, and inertial
      effects. To avoid these difficulties, an inverse method was employed to determine
      the dynamic response of a soft, prospective biomimetic elastomer using Kolsky bar
      tests coupled with high-speed 3D digital image correlation. Individual tests were
      modeled using finite elements, and the dynamic stiffness of the elastomer was
      identified by matching the simulation results with test data using numerical
      optimization. Using this method, the average dynamic response was found to be
      nearly equivalent to the quasi-static response measured with stress-strain curves
      at compressive strains up to 60%, with an uncertainty of +/-18%. Moreover, the
      behavior was consistent with the results in stress relaxation experiments and
      oscillatory tests although the latter were performed at lower strain levels.

PMID- 22982960
TI  - Stepwise construction of grid-type Cu(II)-Cd(II) heterometallic MOFs based on an
      imidazole-appended dipyrrin ligand.
AB  - An imidazole-appended dipyrrin ligand yields, upon coordination to Cu(II)
      cations, a linear metallatecton that self-assembles with Cd(II) salts to afford
      2D grid-type MOFs which, upon parallel stacking, lead to porous crystals offering
      1D channels.

PMID- 22982959
TI  - In situ mechanical behavior of mineral crystals in human cortical bone under
      compressive load using synchrotron X-ray scattering techniques.
AB  - It is of great interest to delineate the effect of orientation distribution of
      mineral crystals on the bulk mechanical behavior of bone. Using a unique
      synergistic approach combining a progressive loading scheme and synchrotron X-ray
      scattering techniques, human cortical bone specimens were tested in compression
      to examine the in situ mechanical behavior of mineral crystals aligned in
      different orientations. The orientation distribution was quantitatively estimated
      by measuring the X-ray diffraction intensity from the (002) plane in mineral
      crystals. In addition, the average longitudinal (c-axis), transverse (a-axis),
      and shear strains of the subset of mineral crystals aligned in each orientation
      were determined by measuring the lattice deformation normal to three distinct
      crystallographic planes (i.e. 002, 310, and 213) in the crystals. The
      experimental results indicated that the in situ strain and stress of mineral
      crystals varied with orientations. The normal strain and stress in the
      longitudinally aligned mineral crystals were markedly greater than those in the
      transversely oriented crystals, whereas the shear stress reached a maximum for
      the crystals aligned in +/-30 degrees  with respect to the loading direction. The
      maximum principal strain and stress were observed in the mineral crystals
      oriented along the loading axis, with a similar trend observed in the maximum
      shear strain and stress. By examining the in situ behavior, the contribution of
      mineral crystals to load bearing and the bulk behavior of bone are discussed.

PMID- 22982961
TI  - The monocyte chemotactic protein synthesis inhibitor bindarit prevents mesangial
      cell proliferation and extracellular matrix remodeling.
AB  - Glomerular expression of chemotactic protein-1/chemokine (C-C motif) ligand-2
      (MCP-1/CCL2) correlates with the degree of renal damage, suggesting a role of
      this chemokine in the pathogenesis of renal diseases. Bindarit is an original
      indazolic derivative able to inhibit MCPs synthesis and to significantly decrease
      MCP-1/CCL2 urinary excretion in patients with Lupus Nephritis, in correlation
      with reduction in albuminuria. Aim of the present work was to elucidate the
      effect of MCP-1/CCL2 synthesis inhibition on in vitro models of mesangial cell
      dysfunction. ET1 (10nM) and AngII (10nM) significantly stimulated MCP-1/CCL2
      release by human renal mesangial cells (HRMCs) after 3-12h stimulation. Bindarit
      (10-300 MUM) significantly inhibited MCP-1/CCL2 release in response to both
      stimuli within 12h. Bindarit also inhibited mRNA MCP-1/CCL2 expression,
      confirming an effect of the drug at transcriptional level. Bindarit significantly
      and concentration-dependently inhibited HRMC proliferation, measured as either
      cell duplication or total DNA/well, and impaired mRNA collagen IV expression,
      collagen deposition and fibronectin expression induced by AngII and ET1. Exposure
      of HRMCs to bindarit also impaired MMP2 activation in response to both stimuli,
      measured by means of gelatin zymography. These data confirm the important role of
      MCP-1/CCL2 synthesis in mesangial cell dysfunction and support the potential of
      therapeutic intervention targeting this chemokine in kidney disease.

PMID- 22982962
TI  - CaMKII and ryanodine receptor as new antiarrhythmic targets.

PMID- 22982963
TI  - To the Editor--Antitachycardia pacing reduces appropriate and inappropriate
      shocks in children and congenital heart disease patients.

PMID- 22982965
TI  - Temporary left ventricular stimulation in patients with refractory cardiogenic
      shock and asynchronous left ventricular contraction: a safety and feasibility
      study.
AB  - BACKGROUND: Despite modern treatment strategies, cardiogenic shock (CS) is still
      associated with high mortality. OBJECTIVE: To evaluate the feasibility and safety
      of temporary percutaneous left ventricular (LV) stimulation as rescue therapy in
      patients with CS refractory to standard clinical care. METHODS: Consecutive
      patients with deteriorating CS without further treatment options received
      transjugular placement of a temporary LV lead if they exhibited signs of
      asynchronous LV contraction. To maintain atrioventricular synchronous
      contraction, an additional right atrial lead was placed in patients with sinus
      rhythm. The leads were externally connected to a conventional pacemaker.
      Hemodynamic course, clinical outcome, and adverse events were assessed. RESULTS:
      A total of 15 patients [ischemic cardiomyopathy (n = 8), dilated cardiomyopathy
      (n = 6), and acute myocarditis (n = 1)] underwent successful lead placement.
      Median procedure and fluoroscopy times measured 60 minutes (interquartile range
      [IQR] 55-90) and 12 minutes (IQR 7-34), respectively. Ten patients (67%) acutely
      responded by improvement of hemodynamic parameters with simultaneous reduction of
      catecholamine support. Catecholamine therapy was discontinued after a median of
      28 hours (IQR 16-60). The temporary leads were removed after a median of 6 days
      (IQR 3-10). Total in-hospital mortality was 47%, measuring 80% in nonresponders
      and 30% in responders (P = .119). There was no therapy-related serious adverse
      event. CONCLUSIONS: Our data indicate that there may be a role for temporary LV
      stimulation as rescue therapy in selected patients with refractory CS. In
      clinical situations where aggressive therapies are used for urgent hemodynamic
      stabilization, temporary LV stimulation may evolve as a further and less invasive
      treatment option.

PMID- 22982966
TI  - Time to recurrence of atrial fibrillation influences outcome following catheter
      ablation.
AB  - BACKGROUND: Outcome after atrial fibrillation (AF) recurrence after ablation
      remains poorly characterized. OBJECTIVE: To determine whether the time to
      recurrence of AF after catheter ablation impacts outcome. METHODS: Four hundred
      thirty-nine consecutive patients with AF after catheter ablation were categorized
      as early recurrence (E) (3-6 months after ablation; n = 245 patients), late (L)
      (6-12 months; n = 118), and very late (VL) (>12 months; n = 76). Subsequent AF
      frequency (defined as rare if <= 2 episodes or <= 1 cardioversion per 6-month
      window), response to antiarrhythmic drugs (AADs), and long-term outcome after
      repeat ablation were evaluated. RESULTS: Subsequent AF episodes were rare in 9%
      of E, 42% of L, and 68% of VL groups (P<.001). AF was eliminated with AADs in 19%
      patients of E, 58% of L, and 72% of VL groups in whom AADs were tried (P<.001). A
      repeat ablation was performed in 75% patients of E, 59% of L, and 46% of VL
      recurrence groups (P<.001). With>1-year follow-up after repeat ablation, 49%
      patients of E, 70% of L, and 89% of VL groups (P<.001) had no or rare AF. In
      multivariate logistic regression, time to recurrence was an independent predictor
      of rare AF episodes, better response to AADs, and better outcome after repeat
      ablation. CONCLUSIONS: In patients with AF after ablation, time to recurrence is
      a major determinant of outcome. Patients with later recurrences are more likely
      to have sporadic episodes and respond better to AADs and repeat ablation. These
      results not only suggest pathophysiologic differences but also have implications
      for counseling patients regarding anticipated outcome.

PMID- 22982967
TI  - Transforming growth factor-beta1 level and outcome after catheter ablation for
      nonparoxysmal atrial fibrillation.
AB  - BACKGROUND: Atrial fibrosis plays a role in the development of a vulnerable
      substrate for atrial fibrillation (AF). Transforming growth factor (TGF)-beta(1)
      is related to the degree of atrial fibrosis and the recurrence of AF after
      surgical maze procedures. Whether TGF-beta(1) is associated with the outcome
      after catheter ablation for AF remains unclear. OBJECTIVE: The purpose of this
      study was to investigate whether plasma TGF-beta(1) was an independent predictor
      of AF recurrence after catheter ablation. METHODS: Two hundred consecutive AF
      patients (154 with paroxysmal AF and 46 with nonparoxysmal AF) underwent catheter
      ablation. Their TGF-beta(1) levels and clinical and echocardiographic data were
      collected before ablation. RESULTS: Thirty patients (65%) with nonparoxysmal AF
      and 57 (37%) with paroxysmal AF had AF recurrence after catheter ablation. Among
      patients with nonparoxysmal AF, those experiencing recurrence had higher TGF
      beta(1) levels than did those who did not experience recurrence (34.63 +/- 11.98
      ng/mL vs 27.33 +/- 9.81 ng/mL; P = .026). In patients with paroxysmal AF,
      recurrence was not associated with different TGF-beta(1) levels. In patients with
      nonparoxysmal AF, TGF-beta(1) levels and left atrial diameter (LAD) were
      independent predictors of AF recurrence after catheter ablation. Moreover, TGF
      beta(1) levels had an incremental value over LAD in predicting AF recurrence
      after catheter ablation (global chi(2) of LAD alone: 6.3; LAD and TGF-beta(1)
      levels: 11.9; increment in global chi(2) = 5.6; P = .013). Patients with small
      LAD and low TGF-beta(1) levels had the lowest AF recurrence rate at 11%.
      CONCLUSION: TGF-beta(1) level is an independent predictor of AF recurrence in
      patients with nonparoxysmal AF and might be useful for identifying those patients
      likely to have better outcomes after catheter ablation.

PMID- 22982968
TI  - There are lots of things about implantable cardioverter-defibrillators that
      should be eliminated: shocks are a good start.

PMID- 22982969
TI  - Noninvasive 3D mapping system guided ablation of anteroseptal pathway below the
      aortic cusp.

PMID- 22982971
TI  - HLA-class II disparity is necessary for effective T cell mediated Graft-versus
      Leukemia effects in NOD/scid mice engrafted with human acute lymphoblastic
      leukemia.

PMID- 22982970
TI  - Carvedilol analogue inhibits triggered activities evoked by both early and
      delayed afterdepolarizations.
AB  - BACKGROUND: Carvedilol and its analogues suppress delayed afterdepolarizations
      (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct
      action on the cardiac ryanodine receptor type 2 (RyR2). OBJECTIVE: To test a
      hypothesis that carvedilol analogue may also prevent triggered activities (TAs)
      through the suppression of early afterdepolarizations (EADs). METHODS:
      Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using
      optical mapping technique in Langendorff-perfused mouse and rabbit hearts to
      study the effect of carvedilol analogue VK-II-36, which does not have significant
      beta-blocking effects. RESULTS: Spontaneous intracellular Ca(2+) elevations
      (SCaEs) during diastole were induced by rapid ventricular pacing and
      isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs
      were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts
      after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and
      eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect
      of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in
      which phase 2 and phase 3 EADs were observed in association with systolic SCaEs.
      VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the
      dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36
      completely prevented EAD-mediated TAs in all ventricles studied. CONCLUSIONS: A
      carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact
      mouse and rabbit ventricles by the suppression of SCaEs, independent of beta
      blocking activity. The RyR2 may be a potential target for treating focal
      ventricular arrhythmias triggered by either EADs or DADs.

PMID- 22982972
TI  - Progressive and accelerated disability onset by race/ethnicity and education
      among late midlife and older adults.
AB  - OBJECTIVE: This study explores the pace of severe disability onset with an
      emphasis on the role of race/ethnicity and education. More specifically, this
      research examines whether race/ethnicity and educational attainment are
      independent predictors of progressive and accelerated disability onset. METHOD:
      Using the Health and Retirement Study (HRS) Waves 2 to 10 (1994-2010), a series
      of discrete-time Cox proportional hazards models with multiple competing events
      were created to ascertain whether respondents developed progressive or
      accelerated disability in subsequent waves. RESULTS: Black and Hispanic
      respondents were at an increased risk of developing progressive disability.
      Respondents without a high school degree were more likely to experience
      progressive or accelerated disability. DISCUSSION: Low educational attainment was
      a particularly strong predictor of accelerated disability onset and may represent
      an acute lack of resources over the life course. Race and ethnicity were
      important predictors of progressive disability onset, which may reflect
      racial/ethnic variations in the disabling process.

PMID- 22982973
TI  - Identification of ovarian gene expression patterns during vitellogenesis in
      Atlantic cod (Gadus morhua).
AB  - Follicular maturational competence and ovulatory competence in teleost fish refer
      to the ability of the ovarian follicle to undergo final oocyte maturation and
      ovulation, respectively, in response to gonadotropin stimulation and other
      external cues. Some gene products related to competence acquisition are likely
      synthesized during vitellogenic growth, as these follicles gain in vivo
      responsiveness to exogenous gonadotropin stimulation and can be induced to
      undergo maturation and ovulation. In Atlantic cod (Gadus morhua), gonadotropin
      responsiveness has been shown to be oocyte size-dependent, and only ovaries
      containing late-stage vitellogenic follicles can be induced to ovulate. The
      purpose of the present study was to compare gene expression patterns between mid
      (unresponsive) and late (responsive) vitellogenic ovaries to identify genes
      involved in gonadotropin responsiveness and the acquisition of maturational and
      ovulatory competencies. Representational difference analysis was conducted in two
      reciprocal comparisons using intact ovarian fragments and follicle wall-enriched
      tissues, and genes of interest were used in real time quantitative PCR to confirm
      differential expression. Few differences were detected in intact ovarian
      fragments, but type IV ice-structuring protein and gephyrin were upregulated
      later in development and may be involved in lipid and sulfur metabolism,
      respectively. Candidate gene assays for luteinizing hormone receptor and
      aromatase also exhibited significant upregulation during vitellogenesis. Many
      genes were differentially expressed in follicle wall-enriched tissues, including
      endocrine maturational regulators and smooth muscle genes. Overall, maturational
      and ovulatory competencies during vitellogenesis in Atlantic cod are associated
      with up- and downregulation of many genes involved in lipid metabolism, endocrine
      regulation, and ovulatory preparation.

PMID- 22982974
TI  - Identification and characterization of the chicken galanin receptor GalR2 and a
      novel GalR2-like receptor (GalR2-L).
AB  - In mammals, the neuropeptide galanin exerts a variety of physiological roles in
      the neuroendocrine system through its interactions with three galanin receptor
      subtypes (GalR1, GalR2 and GalR3). However, little is known about the
      characteristics of galanin receptors in birds, and it is only recently that avian
      GalR1 and a novel GalR1-like receptor were first identified in chickens. In this
      study, we report the cDNA cloning and characterization of the other two chicken
      galanin receptors, the galanin type II receptor (cGalR2) and a novel GalR2-like
      receptor (GalR2-L), which share high degrees of similarity in sequence identity,
      gene structure and signaling properties. cGalR2 and cGalR2-L cDNAs encode two
      putative receptors of 371 and 370 amino acids, in which they show considerable
      amino acid sequence identities (65-67%, and 53-55%, respectively) with the
      mammalian GalR2. RT-PCR assays revealed that cGalR2 and cGalR2-L mRNA were widely
      expressed in the adult chicken tissues including the whole brain, intestine,
      lung, ovary, pituitary and different regions of the oviduct. As assayed with
      different luciferase reporter systems, chicken galanin (cGal 1-29) and human
      galanin-like peptide (hGALP 1-60) were demonstrated to stimulate the luciferase
      activities in Chinese hamster ovary cells expressing cGalR2 and cGalR2-L through
      the activations of cAMP/PKA, Ca(2+)/calcineurin and MAPK/ERK signaling pathways,
      hence suggesting that both receptors are functionally coupled to the G(s) and
      G(q) proteins. Furthermore, the previously identified cGalR1 and cGalR1-L were
      found to be solely coupled to the G(i/o) proteins, and the hGALP (1-60) exhibited
      only a low potency to cGalR1, cGalR1-L, cGalR2 and cGalR2-L activations.

PMID- 22982975
TI  - Strong pituitary and hypothalamic responses to photoperiod but not to 6-methoxy-2
      benzoxazolinone in female common voles (Microtus arvalis).
AB  - The annual cycle of changing day length (photoperiod) is widely used by animals
      to synchronise their biology to environmental seasonality. In mammals, melatonin
      is the key hormonal relay for the photoperiodic message, governing thyroid
      stimulating hormone (TSH) production in the pars tuberalis (PT) of the pituitary
      stalk. TSH acts on neighbouring hypothalamic cells known as tanycytes, which in
      turn control hypothalamic function through effects on thyroid hormone (TH)
      signalling, mediated by changes in expression of the type II and III deiodinases
      (Dio2 and Dio3, respectively). Among seasonally breeding rodents, voles of the
      genus Microtus are notable for a high degree of sensitivity to nutritional and
      social cues, which act in concert with photoperiod to control reproductive
      status. In the present study, we investigated whether the TSH/Dio2/Dio3
      signalling pathway of female common voles (Microtus arvalis) shows a similar
      degree of photoperiodic sensitivity to that described in other seasonal mammal
      species. Additionally, we sought to determine whether the plant metabolite 6
      methoxy-2-benzoxazolinone (6-MBOA), described previously as promoting
      reproductive activation in voles, had any influence on the TSH/Dio2/Dio3 system.
      Our data demonstrate a high degree of photoperiodic sensitivity in this species,
      with no observable effects of 6-MBOA on upstream pituitary/hypothalamic gene
      expression. Further studies are required to characterise how photoperiodic and
      nutritional signals interact to modulate hypothalamic TH signalling pathways in
      mammals.

PMID- 22982976
TI  - Molluscan GnRH associated with reproduction.
AB  - Gonadotropin-releasing hormone (GnRH) is a neuropeptide that has an essential
      role in the neural regulation of vertebrate reproduction. Over the past two
      decades there has been increasing evidence strongly indicating that members of
      the GnRH superfamily, which includes GnRH, adipokinetic hormone (AKH), corazonin
      (Crz) and adipokinetic hormone/corazonin-related peptides (ACP), are almost
      ubiquitous amongst bilateral animals. Moreover GnRH possibly has origins in even
      more ancient, non-bilateral ancestors. Current knowledge about molluscan GnRH has
      been accumulated regarding immunological identification, physiological function
      and sequence analysis. In the present review we summarized a current status of
      molluscan GnRH research and focus on its role in the reproduction of the
      molluscs. In cephalopods and gastropods the presence of a GnRH-like peptide was
      detected with heterologous antibodies and the identified GnRH was suggested to be
      involved with behavior and reproduction. Reproductive roles for GnRH have been
      confirmed in both bivalve and cephalopod molluscs. These findings will provide
      useful insights into the evolution of reproductive endocrinology.

PMID- 22982977
TI  - NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized
      mouse lines and its effect on bioactivation of the carcinogen aristolochic acid
      I.
AB  - Aristolochic acid causes a specific nephropathy (AAN), Balkan endemic
      nephropathy, and urothelial malignancies. Using Western blotting suitable to
      determine protein expression, we investigated in several transgenic mouse lines
      expression of NAD(P)H:quinone oxidoreductase (NQO1)-the most efficient cytosolic
      enzyme that reductively activates aristolochic acid I (AAI). The mouse tissues
      used were from previous studies [Arlt et al., Chem. Res. Toxicol. 24 (2011) 1710;
      Stiborova et al., Toxicol. Sci. 125 (2012) 345], in which the role of microsomal
      cytochrome P450 (CYP) enzymes in AAI metabolism in vivo had been determined. We
      found that NQO1 levels in liver, kidney and lung of Cyp1a1-/-, Cyp1a2-/- and
      Cyp1a1/1a2-/- knockout mouse lines, as well as in two CYP1A-humanized mouse lines
      harboring functional human CYP1A1 and CYP1A2 and lacking the mouse Cyp1a1/1a2
      orthologs, differed from NQO1 levels in wild-type mice. NQO1 protein and enzymic
      activity were induced in hepatic and renal cytosolic fractions isolated from AAI
      pretreated mice, compared with those in untreated mice. Furthermore, this
      increase in hepatic NQO1 enzyme activity was associated with bioactivation of AAI
      and elevated AAI-DNA adduct levels in ex vivo incubations of cytosolic fractions
      with DNA and AAI. In conclusion, AAI appears to increase its own metabolic
      activation by inducing NQO1, thereby enhancing its own genotoxic potential.

PMID- 22982978
TI  - The risk of major elective vascular surgical procedures in patients with end
      stage renal disease.
AB  - OBJECTIVE: To examine the postoperative complications and death rate of major
      elective vascular surgery procedures in patients with end-stage renal disease
      (ESRD). BACKGROUND DATA: Patients with ESRD undergoing elective major vascular
      surgical procedures are thought to have a high rate of postoperative
      complications and death. METHODS: The American College of Surgeons-National
      Surgical Quality Improvement Program database was used to select ESRD and non
      ESRD patients who had elective major vascular surgical procedures between 2004
      and 2008. Multivariable logistic regression analysis was used to examine the
      impact of ESRD on 30-day surgical outcomes adjusted for age, race, sex, work
      relative value units, American Society of Anesthesiology class, and recent
      operations (within the past 30 days). RESULTS: ESRD patients undergoing elective
      major vascular surgery were significantly more likely than non-ESRD patients to
      develop surgical site infection, unplanned intubation, ventilator dependence,
      combined pulmonary outcome, and a need for reoperation within 30 days of surgery.
      Importantly, ESRD patients undergoing elective major vascular surgery were also
      at higher risk for composite outcome and death within 30 days from surgery. ESRD
      patients above age 65 years undergoing elective major vascular surgery had far
      worse 30-day outcomes when compared with the younger ESRD cohort. Examining these
      data by their anatomic site (carotid, aortic, and peripheral) demonstrated
      elevated rates of postoperative complications and death in patients with ESRD
      undergoing open abdominal aortic aneurysm repair, carotid endarterectomies, and
      peripheral vascular operations compared with the non-ESRD cohort. Endovascular
      abdominal aortic aneurysm repair in ESRD patients had complications and death
      rates comparable with non-ESRD patients. CONCLUSIONS: Patients with ESRD
      undergoing elective vascular surgery have a significantly elevated risk of
      postoperative complications and death after major vascular surgical operations-
      particularly in patients over age 65. These data, in combination with well
      established reduced survival for the older ESRD population, call into question
      the utility of most carotid and aortic operations in these patients in the
      absence of symptoms or a rapidly enlarging aneurysm.

PMID- 22982979
TI  - Coding region of adiponectin contains a silent intron reactivated by the adjacent
      intervening sequence of vector.
AB  - Precise splicing pre-mRNA into correct mRNA is a tightly orchestrated process
      involving both cis and trans factors. However, the regulatory mechanism
      underlying alternative splicing remain elusive. An alternative splicing was
      revealed by comparing RT-PCR products (cDNA) of human adiponectin gene (ADPN)
      genes and sequencing the corresponding cDNA recovered from CHO-K1 cells
      transfected with a pIRES-neo vector carrying the cDNA. We determined that an 88
      nt sequence in the original cDNA was missing from the adiponectin mRNA isolated
      from the transfected cells. After analyzing the flanking sequences and context of
      the 88-nt fragment, we discovered that it does have a typical intron
      configuration containing the splicing donor and acceptor, polypyrimidine tract,
      and branch site. A point mutation at the acceptor site (AG->TG) abolishes this
      splicing site indicating that it is a bona fide intron. The intron splicing
      defaulted again when the adjacent intervening sequence (IVS) of pIRES-neo was
      deleted or adiponectin 3'-UTR was present. We found that 3'-UTR segment contained
      several splicing silencers and IVS contained high density of splicing enhancers.
      It explained the reactivation of this silent intron. Our results elicited the
      possibility that a 3'-UTR-free cDNA may reactivate an otherwise silent intron in
      the coding region as it is cloned for expression in mammalian cells.

PMID- 22982980
TI  - Results from a prospective, international, epidemiologic study of invasive
      candidiasis in children and neonates.
AB  - BACKGROUND: Candida species are the third most common cause of pediatric health
      care-associated bloodstream infection in the United States and Europe. To our
      knowledge, this report from the International Pediatric Fungal Network is the
      largest prospective, multicenter observational study dedicated to pediatric and
      neonatal invasive candidiasis. METHODS: From 2007 to 2011, we enrolled 196
      pediatric and 25 neonatal patients with invasive candidiasis. RESULTS: Non
      albicans Candida species predominated in pediatric (56%) and neonatal (52%) age
      groups, yet Candida albicans was the most common species in both groups.
      Successful treatment responses were observed in pediatric (76%) and neonatal
      patients (92%). Infection with Candida parapsilosis led to successful responses
      in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida
      glabrata was associated with a lower successful outcome in pediatric patients
      (55%). The most commonly used primary antifungal therapies for pediatric invasive
      candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin
      (18%). Outcome of pediatric invasive candidiasis was similar in response to
      polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used
      primary antifungal therapies for neonatal invasive candidiasis were fluconazole
      (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%).
      Outcomes of neonatal candidiasis by antifungal class again revealed similar
      response rates among the classes. CONCLUSIONS: We found a predominance of non
      albicans Candida infection in children and similar outcomes based on antifungal
      class used. This international collaborative study sets the foundation for large
      epidemiologic studies focusing on the unique features of neonatal and pediatric
      candidiasis and comparative studies of therapeutic interventions in these
      populations.

PMID- 22982981
TI  - Microsporidia and coccidia as causes of persistence diarrhea among liver
      transplant children:  incidence rate and species/genotypes.
AB  - We determined species/genotype(s) of enteric microsporidia and coccidia causing
      diarrhea among 44 liver transplant children in Shiraz Nemazee hospital using acid
      fast-trichrome staining and polymerase chain reaction-sequencing techniques.
      Enterocytozoon bieneusi (genotype D), Cryptosporidium (parvum and meleagridis)
      were detected in 6.81% and 11.36% of the children, respectively.

PMID- 22982982
TI  - Fatal wild-type varicella-zoster virus encephalitis without a rash in a
      vaccinated child.
AB  - Encephalitis associated with varicella-zoster virus, rare among children in the
      varicella vaccine era, has generally been associated with a rash. We report fatal
      wild-type varicella-zoster virus encephalitis without a rash in a child who had
      received 1 dose of varicella vaccine. Varicella-zoster virus encephalitis should
      be considered in the differential diagnosis for children presenting with acute
      neurologic symptoms, even vaccine recipients.

PMID- 22982983
TI  - Biomimetic Fabrication of Genetically-Engineered Collagen Peptide-Assembled
      Freestanding Films Reinforced by Quantum Dot Joints.
AB  - Genetically-engineered collagen peptides were assembled into freestanding films
      when QDs are co-assembled as joints between collagen domains. These peptide based
      films show excellent mechanical properties with Young's modulus of ~20 GPa, much
      larger than most of multi-composite polymer films and previously reported
      freestanding nanoparticle-assembled sheets, and it is even close to the bone
      tissue in nature. These films show little permanent deformation under small
      indentation while the mechanical hysteresis becomes remarkable when the load
      approaches near and beyond the rupture point, which is also characteristic to the
      bone tissue.

PMID- 22982984
TI  - Connexin45 provides optimal atrioventricular nodal conduction in the adult mouse
      heart.
AB  - RATIONALE: The gap junctional protein connexin (Cx) 45 is strongly expressed in
      the early embryonic myocardium. In the adult hearts of mice and humans, the
      expression mainly is restricted to the cardiac conduction system. Cx45 plays an
      essential role for development and function of the embryonic heart because
      general and cardiomyocyte-directed deficiencies of Cx45 in mice lead to embryonic
      lethality attributable to morphological and functional cardiovascular defects.
      The function of Cx45 in the adult mouse has not yet been cleared. OBJECTIVE: To
      clarify the function of Cx45 in the adult mouse heart. METHODS AND RESULTS: To
      circumvent the embryonic lethality resulting from Cx45 deficiency, mice were
      generated in which deletion of Cx45 specifically was induced in cardiomyocytes of
      adult mice. These Cx45-deficient mice were viable but showed a decrease in
      atrioventricular nodal conductivity. In addition, the Cx30.2 protein that is
      coexpressed with Cx45 in the cardiac conduction system was posttranscriptionally
      reduced by 70% in mutant hearts. Furthermore, deletion of both Cx45 and Cx30.2
      resulted in viable mice that, however, showed stronger impairment of
      atrioventricular nodal conduction than the single Cx45-deficient mice.
      CONCLUSIONS: Cx45 is required for optimal impulse propagation in the
      atrioventricular node and stabilizes the level of the coexpressed Cx30.2 protein
      in the adult mouse heart. In contrast to the embryo, Cx45 is not essential for
      the viability of adult mice.

PMID- 22982985
TI  - Acute liver carnitine palmitoyltransferase I overexpression recapitulates reduced
      palmitate oxidation of cardiac hypertrophy.
AB  - RATIONALE: Muscle carnitine palmitoyltransferase I is predominant in the heart,
      but the liver isoform (liver carnitine palmitoyltransferase I [L-CPT1]) is
      elevated in hearts with low long chain fatty acid oxidation, such as fetal and
      hypertrophied hearts. OBJECTIVE: This work examined the effect of acute L-CPT1
      expression on the regulation of palmitate oxidation and energy metabolism in
      intact functioning rat hearts for comparison with findings in hypertrophied
      hearts. METHODS AND RESULTS: L-CPT1 was expressed in vivo in rat hearts by
      coronary perfusion of Adv.cmv.L-CPT1 (L-CPT1, n=15) vs. phosphate-buffered saline
      (PBS) infusion (PBS, n=7) or empty virus (empty, n=5). L-CPT1 was elevated 5-fold
      at 72 hours after Adv.cmv.L-CPT1 infusion (P<0.05), but muscle carnitine
      palmitoyltransferase I was unaffected. Despite similar tricarboxylic acid cycle
      rates, palmitate oxidation rates were reduced with L-CPT1 (1.12 +/- 0.29
      MUmol/min per gram of dry weight, mean+/-SE) vs. PBS (1.6 +/- 0.34). Acetyl CoA
      production from palmitate was reduced with L-CPT1 (69 +/- 0.02%; P<0.05; PBS=79
      +/- 0.01%; empty=81 +/- 0.02%), similar to what occurs in hypertrophied hearts,
      and with no difference in malonyl CoA content. Glucose oxidation was elevated
      with L-CPT1 (by 60%). Surprisingly, L-CPT1 hearts contained elevated atrial
      natriuretic peptide, indicating induction of hypertrophic signaling. CONCLUSIONS:
      The results link L-CPT1 expression to reduced palmitate oxidation in a
      nondiseased adult heart, recapitulating the phenotype of reduced long chain fatty
      acid oxidation in cardiac hypertrophy. The implications are that L-CPT1
      expression induces metabolic remodeling hypertrophic signaling and that
      regulatory factors beyond malonyl CoA in the heart regulate long chain fatty acid
      oxidation via L-CPT1.

PMID- 22982987
TI  - High prevalence of serrated polyposis syndrome in FIT-based colorectal cancer
      screening programmes.

PMID- 22982986
TI  - Novel role of HAX-1 in ischemic injury protection involvement of heat shock
      protein 90.
AB  - RATIONALE: Ischemic heart disease is characterized by contractile dysfunction and
      increased cardiomyocyte death, induced by necrosis and apoptosis. Increased cell
      survival after an ischemic insult is critical and depends on several cellular
      pathways, which have not been fully elucidated. OBJECTIVE: To test the hypothesis
      that the anti-apoptotic hematopoietic lineage substrate-1-associated protein X-1
      (HAX-1), recently identified as regulator of cardiac Ca cycling, also may
      ameliorate cellular injury with an ischemic insult. METHODS AND RESULTS: We
      report that cardiac ischemia/reperfusion injury is associated with significant
      decreases in HAX-1 levels ex vivo and in vivo. Accordingly, overexpression of HAX
      1 improved contractile recovery, coupled with reduced infarct size, plasma
      troponin I level, and apoptosis. The beneficial effects were associated with
      decreased endoplasmic reticulum (ER) stress response through specific inhibition
      of the inositol-requiring enzyme (IRE-1) signaling pathway, including its
      downstream effectors caspase-12 and the transcription factor C/EBP homologous
      protein. Conversely, HAX-1 heterozygous-deficient hearts exhibited increases in
      infarct size and IRE-1 activity. The inhibitory effects of HAX-1 were mediated by
      its binding to the N-terminal fragment of the heat shock protein 90 (Hsp90).
      Moreover, HAX-1 sequestered Hsp90 from IRE-1 to the phospholamban
      sarcoplasmic/endoplasmic reticulum calcium ATPase complex. The HAX-1 regulation
      was further supported by loss of IRE-1 inhibition in presence of the Hsp90
      inhibitor, 17-N-allylamino-17-demethoxygeldanamycin. CONCLUSIONS: Cardiac
      ischemia-reperfusion injury is associated with decreases in HAX-1 levels.
      Consequently, overexpression of HAX-1 promotes cardiomyocyte survival, mediated
      by its interaction with Hsp90 and specific inhibition of IRE-1 signaling at the
      ER/sarcoplasmic reticulum.

PMID- 22982988
TI  - A dramatic finding at colonoscopy: cause for concern? Diagnosis: Cat scratch
      colon.

PMID- 22982989
TI  - Studies on the regioselectivity and kinetics of the action of trypsin on
      proinsulin and its derivatives using mass spectrometry.
AB  - Human M-proinsulin was cleaved by trypsin at the R(31)R(32)-E(33) and K(64)R(65)
      G(66) bonds (B/C and C/A junctions), showing the same cleavage specificity as
      exhibited by prohormone convertases 1 and 2 respectively. Buffalo/bovine M
      proinsulin was also cleaved by trypsin at the K(59)R(60)-G(61) bond but at the
      B/C junction cleavage occurred at the R(31)R(32)-E(33) as well as the R(31)
      R(32)E(33) bond. Thus, the human isoform in the native state, with a 31 residue
      connecting C-peptide, seems to have a unique structure around the B/C and C/A
      junctions and cleavage at these sites is predominantly governed by the structure
      of the proinsulin itself. In the case of both the proinsulin species the cleavage
      at the B/C junction was preferred (65%) over that at the C/A junction (35%)
      supporting the earlier suggestion of the presence of some form of secondary
      structure at the C/A junction. Proinsulin and its derivatives, as natural
      substrates for trypsin, were used and mass spectrometric analysis showed that the
      k(cat.)/K(m) values for the cleavage were most favourable for the scission of the
      bonds at the two junctions (1.02+/-0.08*10(5)s(-1)M(-1)) and the cleavage of the
      K(29)-T(30) bond of M-insulin-RR (1.3+/-0.07*10(5)s(-1)M(-1)). However, the K(29)
      T(30) bond in M-insulin, insulin as well as M-proinsulin was shielded from attack
      by trypsin (k(cat.)/K(m) values around 1000s(-1)M(-1)). Hence, as the
      biosynthetic path follows the sequence; proinsulin->insulin-RR->insulin, the
      K(29)-T(30) bond becomes shielded, exposed then shielded again respectively.

PMID- 22982990
TI  - Cross-neutralization of influenza A viruses mediated by a single antibody loop.
AB  - Immune recognition of protein antigens relies on the combined interaction of
      multiple antibody loops, which provide a fairly large footprint and constrain the
      size and shape of protein surfaces that can be targeted. Single protein loops can
      mediate extremely high-affinity binding, but it is unclear whether such a
      mechanism is available to antibodies. Here we report the isolation and
      characterization of an antibody called C05, which neutralizes strains from
      multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and
      electron microscopy structures show that C05 recognizes conserved elements of the
      receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of
      the haemagglutinin receptor-binding site is dominated by a single heavy-chain
      complementarity-determining region 3 loop, with minor contacts from heavy-chain
      complementarity-determining region 1, and is sufficient to achieve nanomolar
      binding with a minimal footprint. Thus, binding predominantly with a single loop
      can allow antibodies to target small, conserved functional sites on otherwise
      hypervariable antigens.

PMID- 22982991
TI  - A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral
      responses.
AB  - Antiviral responses must be tightly regulated to defend rapidly against infection
      while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial
      mediators of antiviral responses and their transcription is regulated by a
      variety of transcription factors; principal among these is the family of
      interferon regulatory factors (IRFs). The IRF gene regulatory networks are
      complex and contain multiple feedback loops. The tools of systems biology are
      well suited to elucidate the complex interactions that give rise to precise
      coordination of the interferon response. Here we have used an unbiased systems
      approach to predict that a member of the forkhead family of transcription
      factors, FOXO3, is a negative regulator of a subset of antiviral genes. This
      prediction was validated using macrophages isolated from Foxo3-null mice. Genome
      wide location analysis combined with gene deletion studies identified the Irf7
      gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator
      of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I
      form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3
      IRF7 regulatory circuit represents a novel mechanism for establishing the
      requisite set points in the interferon pathway that balances the beneficial
      effects and deleterious sequelae of the antiviral response.

PMID- 22982993
TI  - Are the 2010 guidelines on cardiopulmonary resuscitation lost in translation? A
      call for increased focus on implementation science.
AB  - Despite significant resources spent on rigorous evidence review and resuscitation
      guideline development, an important gap remains in our understanding of effective
      strategies and tools for implementing resuscitation guidelines. The lack of
      evidence about effective guideline implementation for resuscitation is likely
      reducing the impact of the incredible amount of work that goes into the
      production of such guidelines. This commentary draws attention to knowledge
      translation learnings from other content areas and within the area of
      resuscitation science to support a call for increased attention and innovation in
      implementation science as an equally important investment for the future of
      resuscitation medicine.

PMID- 22982994
TI  - Exceptions to an absolute rule.

PMID- 22982996
TI  - Cell-autonomous circadian DNA damage response: is the case closed?

PMID- 22982997
TI  - Autophagy and tumor cell invasion.

PMID- 22982998
TI  - Transcriptional profiling of apoptosis: cell death classification moves toward
      the systems era.

PMID- 22982992
TI  - FTO genotype is associated with phenotypic variability of body mass index.
AB  - There is evidence across several species for genetic control of phenotypic
      variation of complex traits, such that the variance among phenotypes is genotype
      dependent. Understanding genetic control of variability is important in
      evolutionary biology, agricultural selection programmes and human medicine, yet
      for complex traits, no individual genetic variants associated with variance, as
      opposed to the mean, have been identified. Here we perform a meta-analysis of
      genome-wide association studies of phenotypic variation using ~170,000 samples on
      height and body mass index (BMI) in human populations. We report evidence that
      the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which
      is known to be associated with obesity (as measured by mean BMI for each
      rs7202116 genotype), is also associated with phenotypic variability. We show that
      the results are not due to scale effects or other artefacts, and find no other
      experiment-wise significant evidence for effects on variability, either at loci
      other than FTO for BMI or at any locus for height. The difference in variance for
      BMI among individuals with opposite homozygous genotypes at the FTO locus is
      approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard
      deviation of weight. Our results indicate that genetic variants can be discovered
      that are associated with variability, and that between-person variability in
      obesity can partly be explained by the genotype at the FTO locus. The results are
      consistent with reported FTO by environment interactions for BMI, possibly
      mediated by DNA methylation. Our BMI results for other SNPs and our height
      results for all SNPs suggest that most genetic variants, including those that
      influence mean height or mean BMI, are not associated with phenotypic variance,
      or that their effects on variability are too small to detect even with samples
      sizes greater than 100,000.

PMID- 22982999
TI  - p53-Aurora A mitotic feedback loop regulates cell cycle progression and genomic
      stability.

PMID- 22983000
TI  - Wee1-Hsp90 inhibitor combination treatment: molecular therapy with potentially
      broad applicability.

PMID- 22983001
TI  - Cisplatin-induced apoptosis and development of resistance are transcriptionally
      distinct processes.

PMID- 22983002
TI  - Packaging host RNAs in small RNA viruses: an inevitable consequence of an error
      prone polymerase?

PMID- 22983003
TI  - Restoring PML tumor suppression to combat cancer.

PMID- 22983004
TI  - Stress granules: the last refuge of TORC1?

PMID- 22983005
TI  - The cellular architecture of multiple myeloma.

PMID- 22983006
TI  - Role for caspase-2 during pore-forming toxin-mediated apoptosis.

PMID- 22983007
TI  - Loss of p53 exacerbates multiple myeloma phenotype by facilitating the
      reprogramming of hematopoietic stem/progenitor cells to malignant plasma cells by
      MafB.
AB  - Multiple myeloma (MM) is a serious, mostly incurable human cancer of malignant
      plasma cells. Chromosomal translocations affecting MAFB are present in a
      significant percentage of multiple myeloma patients. Genetically engineered Sca1
      MafB mice, in which MafB expression is limited to hematopoietic stem/progenitor
      cells (HS/P-Cs), display the phenotypic features of MM. Contrary to many other
      types of cancer, it is not yet known if the p53 gene plays any essential role in
      the pathogenesis of this disease. Here, we show, taking advantage of the Sca1
      MafB MM mouse model, that loss of p53 does not rescue the multiple myeloma
      disease, but instead accelerates its development and exacerbates the MM
      phenotype. Therefore, the efficiency of the MafB-induced MM reprogramming of
      normal HS/P-Cs to terminally differentiated malignant plasma cells is enhanced by
      p53 deficiency, in analogy to what happens in reprogramming to pluripotency.
      These results raise caution about interfering with p53 function when treating
      multiple myeloma.

PMID- 22983008
TI  - The transcription factor CREBZF is a novel positive regulator of p53.
AB  - CREBZF is a member of the mammalian ATF/CREB family of transcription factors.
      Here, we describe a novel functional interaction between CREBZF and the tumor
      suppressor p53. CREBZF was identified in a yeast two-hybrid screen using HEY1,
      recently characterized as an indirect p53 activator, as bait. CREBZF interacts in
      vitro with both HEY1 and p53, and CREBZF expression stabilizes and activates p53.
      Moreover, CREBZF cooperates synergistically with HEY1 to enhance p53
      transcriptional activity. On the other hand, partial depletion of endogenous
      CREBZF diminishes p53 protein levels and inhibits HEY1-mediated activation of
      p53. CREBZF-positive effects on p53 signaling may reflect, at least in part, an
      observed induction of posttranslational modifications in p53 known to prevent its
      degradation. CREBZF expression protects HCT116 cells from UV radiation-induced
      cell death. In addition, CREBZF expression confers sensitivity to 5-fluorouracil,
      a p53-activating chemotherapeutic drug. Our study suggests that CREBZF may
      participate in the modulation of p53 tumor suppressor function.

PMID- 22983009
TI  - The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation.
AB  - Rhabdomyosarcoma (RMS) is a pediatric tumor that arises from muscle precursor
      cells. RMS cells express several markers of early myogenic differentiation, but
      they fail to complete both differentiation program and cell cycle arrest,
      resulting in uncontrolled proliferation and incomplete myogenesis. Previous
      studies showed that EZH2, which is involved in both differentiation and cancer
      progression, is overexpressed in RMS, but a functional binding between its
      expression and its functional role in tumor formation or progression has not yet
      been demonstrated. We hypothesized that EZH2 is a key regulator of muscular
      differentiation program in RMS cells.   In this study, we demonstrated that EZH2
      directly binds muscle specific genes in RD cells. Silencing of EZH2 promotes the
      recruitment of a multiprotein complex at muscle-specific promoters, their
      transcriptional activation and protein expression. Moreover, we demonstrated that
      EZH2 is directly involved in transcriptional repression of MyoD, the main factor
      promoting myogenesis. EZH2 ablation induces MyoD activation the recovery of its
      binding on muscle-specific genes.

PMID- 22983011
TI  - Microdistribution of tetrodotoxin in two species of blue-ringed octopuses
      (Hapalochlaena lunulata and Hapalochlaena fasciata) detected by fluorescent
      immunolabeling.
AB  - Blue-ringed octopuses (genus Hapalochlaena) possess the potent neurotoxin
      tetrodotoxin (TTX). We examined the microdistribution of TTX in ten tissues of
      Hapalochlaena lunulata and Hapalochlaena fasciata by immunolabeling for
      fluorescent light microscopy (FLM). We visualized TTX throughout the posterior
      salivary gland, but the toxin was concentrated in cells lining the secretory
      tubules within the gland. Tetrodotoxin was present just beneath the epidermis of
      the integument (mantle and arms) and also concentrated in channels running
      through the dermis. This was suggestive of a TTX transport mechanism in the blood
      of the octopus, which would also explain the presence of the toxin in the blood
      rich brachial hearts, gills, nephridia, and highly vascularized Needham's sac
      (testes contents). We also present the first report of TTX in any cephalopod
      outside of the genus Hapalochlaena. A specimen of Octopus bocki from French
      Polynesia contained a small amount of TTX in the digestive gland.

PMID- 22983010
TI  - Novel transglutaminase-like peptidase and C2 domains elucidate the structure,
      biogenesis and evolution of the ciliary compartment.
AB  - In addition to their role in motility, eukaryotic cilia serve as a distinct
      compartment for signal transduction and regulatory sequestration of biomolecules.
      Recent genetic and biochemical studies have revealed an extraordinary diversity
      of protein complexes involved in the biogenesis of cilia during each cell cycle.
      Mutations in components of these complexes are at the heart of human ciliopathies
      such as Nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS), Bardet-Biedl
      syndrome (BBS) and Joubert syndrome (JBTS). Despite intense studies, proteins in
      some of these complexes, such as the NPHP1-4-8 and the MKS, remain poorly
      understood. Using a combination of computational analyses we studied these
      complexes to identify novel domains in them which might throw new light on their
      functions and evolutionary origins. First, we identified both catalytically
      active and inactive versions of transglutaminase-like (TGL) peptidase domains in
      key ciliary/centrosomal proteins CC2D2A/MKS6, CC2D2B, CEP76 and CCDC135. These
      ciliary TGL domains appear to have originated from prokaryotic TGL domains that
      act as peptidases, either in a prokaryotic protein degradation system with the
      MoxR AAA+ ATPase, the precursor of eukaryotic dyneins and midasins, or in a
      peptide-ligase system with an ATP-grasp enzyme comparable to tubulin-modifying
      TTL proteins. We suggest that active ciliary TGL proteins are part of a cilia
      specific peptidase system that might remove tubulin modifications or cleave cilia
      localized proteins, while the inactive versions are likely to bind peptides and
      mediate key interactions during ciliogenesis. Second, we observe a vast radiation
      of C2 domains, which are key membrane-localization modules, in multiple ciliary
      proteins, including those from the NPHP1-4-8 and the MKS complexes, such as
      CC2D2A/MKS6, RPGRIP1, RPGRIP1L, NPHP1, NPHP4, C2CD3, AHI1/Jouberin and CEP76,
      most of which can be traced back to the last common eukaryotic ancestor.
      Identification of these TGL and C2 domains aid in the proper reconstruction of
      the Y-shaped linkers, which are key structures in the transitional zone of cilia,
      by allowing precise prediction of the multiple membrane-contacting and protein
      protein interaction sites in these structures. These findings help decipher key
      events in the evolutionary separation of the ciliary and nuclear compartments in
      course of the emergence of the eukaryotic cell.

PMID- 22983012
TI  - PSP toxin release from the cyanobacterium Raphidiopsis brookii D9 (Nostocales)
      can be induced by sodium and potassium ions.
AB  - Paralytic shellfish poisoning (PSP) toxins are a group of naturally occurring
      neurotoxic alkaloids produced among several genera of primarily freshwater
      cyanobacteria and marine dinoflagellates. Although saxitoxin (STX) and analogs
      are all potent Na(+) channel blockers in vertebrate cells, the functional role of
      these compounds for the toxigenic microorganisms is unknown. Based upon the known
      importance of monovalent cations (such as sodium) in the maintenance of cellular
      homeostasis and ion channel function, we examined the effect of high
      extracellular concentrations of these ions on growth, cellular integrity, toxin
      production and release to the external medium in the filamentous freshwater
      cyanobacterium, Raphidiopsis brookii D9; a gonyautoxins (GTX2/3) and STX
      producing toxigenic strain. We observed a toxin export in response to high (17
      mM) NaCl and KCl concentrations in the growth medium that was not primarily
      related to osmotic stress effects, compared to the osmolyte mannitol. Addition of
      exogenous PSP toxins with the same compositional profile as the one produced by
      R. brookii D9 was able to partially mitigate this effect of high Na+ (17 mM). The
      PSP toxin biosynthetic gene cluster (sxt) in D9 has two genes (sxtF and sxtM)
      that encode for a MATE (multidrug and toxic compound extrusion) transporter. This
      protein family, represented by NorM in the bacterium Vibrio parahaemolyticus,
      confers resistance to multiple cationic toxic agents through Na+/drug
      antiporters. Conserved domains for Na+ and drug recognition have been described
      in NorM. For the D9 sxt cluster, the Na+ recognition domain is conserved in both
      SxtF and SxtM, but the drug recognition domain differs between them. These
      results suggest that PSP toxins are exported directly in response to the presence
      of monovalent cations (Na+, K+) at least at elevated concentrations. Thus, the
      presence of both genes in the sxt cluster from strain D9 can be explained as a
      selective recognition mechanism by the SxtF/M transporters for GTX2/3 and STX. We
      propose that these toxins in cyanobacteria could act extracellularly as a
      protective mechanism to ensure homeostasis against extreme salt variation in the
      environment.

PMID- 22983014
TI  - Recurrent erythema annulare centrifugum during ustekinumab treatment in a
      psoriatic patient.

PMID- 22983013
TI  - Toxicology, biodistribution and shedding profile of a recombinant measles vaccine
      vector expressing HIV-1 antigens, in cynomolgus macaques.
AB  - As a new human immunodeficiency virus type 1 (HIV-1) vaccine approach, the live
      attenuated measles virus (MV) Schwarz vaccine strain was genetically engineered
      to express the F4 antigen (MV1-F4). F4 is a fusion protein comprising HIV-1
      antigens p17 and p24, reverse transcriptase and Nef. This study assessed the
      toxicity, biodistribution and shedding profiles of MV1-F4. Cynomolgus macaques
      were intramuscularly immunized one or three times with the highest dose of MV1-F4
      intended for clinical use, the reference (Schwarz) measles vaccine or saline, and
      monitored clinically for 11 or 85 days. Toxicological parameters included local
      and systemic clinical signs, organ weights, haematology, clinical and gross
      pathology and histopathology. Both vaccines were well tolerated, with no
      morbidity, clinical signs or gross pathological findings observed. Mean spleen
      weights were increased after three doses of either vaccine, which corresponded
      with increased numbers and/or sizes of germinal centers. This was likely a result
      of the immune response to the vaccines. Either vaccine virus replicated
      preferentially in secondary lymphoid organs and to a lesser extent in epithelium
      rich tissues (e.g., intestine, urinary bladder and trachea) and the liver. At the
      expected peak of viremia, viral RNA was detected in some biological fluid samples
      from few animals immunized with either vaccine, but none of these samples
      contained infectious virus. In conclusion, no shedding of infectious viral
      particles was identified in cynomolgus monkeys after injection of MV1-F4 or
      Schwarz measles vaccines. Furthermore, no toxic effect in relation to the MV
      vaccination was found with these vaccines in this study.

PMID- 22983016
TI  - Combining magnifying prismatic lens with wide-angle viewing system to enhance
      view of peripheral retina during vitreous surgery.

PMID- 22983015
TI  - Phase I study of nelfinavir in liposarcoma.
AB  - PURPOSE: HIV protease inhibitors are associated with HIV protease inhibitor
      related lipodystrophy syndrome. We hypothesized that liposarcomas would be
      similarly susceptible to the apoptotic effects of an HIV protease inhibitor,
      nelfinavir. METHODS: We conducted a phase I trial of nelfinavir for liposarcomas.
      There was no limit to prior chemotherapy. The starting dose was 1,250 mg twice
      daily (Level 1). Doses were escalated in cohorts of three to a maximally
      evaluated dose of 4,250 mg (Level 5). One cycle was 28 days. Steady-state
      pharmacokinetics (PKs) for nelfinavir and its primary active metabolite, M8, were
      determined at Levels 4 (3,000 mg) and 5. RESULTS: Twenty subjects (13 males) were
      enrolled. Median (range) age was 64 years (37-81). One subject at Level 1
      experienced reversible, grade 3 pancreatitis after 1 week and was replaced. No
      other dose-limiting toxicities were observed. Median (range) number of cycles was
      3 (0.6-13.5). Overall best responses observed were 1 partial response, 1 minor
      response, 4 stable disease, and 13 progressive disease. Mean peak plasma levels
      and AUCs for nelfinavir were higher at Level 4 (7.3 mg/L; 60.9 mg/L * h) than 5
      (6.3 mg/L; 37.7 mg/L * h). The mean ratio of M8:nelfinavir AUCs for both levels
      was ~1:3. CONCLUSIONS: PKs demonstrate auto-induction of nelfinavir clearance at
      the doses studied, although the mechanism remains unclear. Peak plasma
      concentrations were within range where anticancer activity was demonstrated in
      vitro. M8 metabolite is present at ~1/3 the level of nelfinavir and may also
      contribute to the anticancer activity observed.

PMID- 22983017
TI  - Resolution of the diagnosis and maternal sensitivity among mothers of children
      with Intellectual Disability.
AB  - We examined mothers' resolution of their children's diagnosis of Intellectual
      Disability (ID) and its link to maternal sensitivity, and we hypnotized that
      mothers' who are "resolved" will show more sensitivity during their interactions
      with their children than "unresolved" mothers. We assessed maternal resolution
      using the Reaction to Diagnosis Interview and maternal sensitivity in three
      different play episodes using the Emotional Availability Scales. Our sample
      included 40 children between the ages of 2.5 and 5.5 with clinical diagnoses of
      non-syndromic ID and their mothers. Supporting our hypothesis we found that
      mothers who were resolved regarding the diagnosis of their children showed more
      maternal sensitivity to their children in two of the three play episodes. Another
      important finding was that resolution and sensitivity were associated even when
      we controlled for the child's responsiveness to and involvement with the mother,
      suggesting that the link between resolution and sensitivity cannot be accounted
      by the impact of the child's behavior on the mother.

PMID- 22983018
TI  - Impact of a structured template and staff training on compliance and quality of
      clinical handover.
AB  - INTRODUCTION: Change in junior doctors working pattern has brought effective and
      safe clinical handover into a central role to ensure the patient safety and high
      quality care. We investigated whether the compliance and quality of clinical
      handover could be improved through the use of a standardised and structured
      handover template. METHODS: A computerised template was developed in accordance
      with handover guidelines provided by the Royal College of Surgeons of England.
      Pre- and post-intervention audits against an eleven-point dataset pertaining to
      the handover of acute surgical admissions were undertaken. The results from the
      two discrete audits periods were compared to examine the impact of intervention.
      RESULTS: There were 137 acute surgical admissions during pre-intervention and 155
      admissions in post-intervention audit period. A significant improvement in
      overall handover practice was observed in post-intervention period. The
      documentation of patient hospital number (84 (61%) vs. 132 (85%) p<0.001), past
      medical history (39 (28%) vs. 75 (48%) p<0.001) and patient assessment by a
      senior member of the on-call team (3 (2%) vs. 125 (85%) p<0.001) all demonstrated
      significant improvements upon use of structured template. Compliance to effective
      handover improved following increased awareness of the importance of safe
      clinical handover among the junior doctors. CONCLUSION: Implementation of a
      standardised guideline-based structured handover template and training of junior
      doctors are likely to improve compliance to agreed standards, promote quality of
      care, and protect patient safety.

PMID- 22983019
TI  - Resident work hour reforms: implications regarding hip fracture surgery.
AB  - BACKGROUND: Resident work hour reforms were developed by Aga Khan University
      Postgraduate Medical education committee in the year 2005. These reforms were
      implemented by the section of Orthopedics in winter 2006. We designed this study
      to determine if there is a difference in morbidity and mortality following
      Dynamic Hip Screw (DHS) fixation for intertrochanteric fracture patients before
      and after implementation of work hour reforms. METHODS: Patients who underwent
      DHS fixation for inter-trochanteric fracture from January 2005 to December 2008
      were included. These patients were divided into two groups. Group A included
      those patients who underwent DHS fixation prior to the implementation of work
      hour reforms and Group B patients had their hip fracture surgery after the
      implementation of these reforms. RESULTS: The mean operative time was 1.6+/-0.6 h
      and 1.3+/-0 h for group A and B patients respectively (p<0.001). There was no
      change in the rates of wound infection, length of hospital stay, post operative
      ambulation status, inadequate fixation, repeat surgeries and mortality in the two
      groups. CONCLUSION: Resident work hour reform was associated with a significant
      decrease in the mean operative time for patients undergoing DHS fixation. However
      morbidity and mortality following DHS fixation for Intertrochanteric fractures
      has not decreased after implementation of these reforms. Further research
      evaluating patient outcomes in orthopedic surgery following work-hour
      restrictions are needed. Moreover, the impact of these reforms on the educational
      and research activities of the residents also needs to be determined.

PMID- 22983020
TI  - Rapid hydrothermal flow synthesis and characterisation of carbonate- and silicate
      substituted calcium phosphates.
AB  - A range of crystalline and nano-sized carbonate- and silicate-substituted
      hydroxyapatite has been successfully produced by using continuous hydrothermal
      flow synthesis technology. Ion-substituted calcium phosphates are better
      candidates for bone replacement applications (due to improved bioactivity) as
      compared to phase-pure hydroxyapatite. Urea was used as a carbonate source for
      synthesising phase pure carbonated hydroxyapatite (CO3-HA) with ~5 wt%
      substituted carbonate content (sample 7.5CO3-HA) and it was found that a further
      increase in urea concentration in solution resulted in biphasic mixtures of
      carbonate-substituted hydroxyapatite and calcium carbonate. Transmission electron
      microscopy images revealed that the particle size of hydroxyapatite decreased
      with increasing urea concentration. Energy-dispersive X-ray spectroscopy result
      revealed a calcium deficient apatite with Ca:P molar ratio of 1.45 (+/-0.04) in
      sample 7.5CO3-HA. For silicate-substituted hydroxyapatite (SiO4-HA) silicon
      acetate was used as a silicate ion source. It was observed that a substitution
      threshold of ~1.1 wt% exists for synthesis of SiO4-HA in the continuous
      hydrothermal flow synthesis system, which could be due to the decreasing yields
      with progressive increase in silicon acetate concentration. All the as
      precipitated powders (without any additional heat treatments) were analysed using
      techniques including Transmission electron microscopy, X-ray powder diffraction,
      Differential scanning calorimetry, Thermogravimetric analysis, Raman spectroscopy
      and Fourier transform infrared spectroscopy.

PMID- 22983021
TI  - Self-assembled photosensitizer-conjugated nanoparticles for targeted photodynamic
      therapy.
AB  - An effective tumor-targeted drug delivery system for photodynamic therapy was
      developed by designing ligand-mediated nanoparticles with stable formulations of
      a hydrophobic photosensitizer. Novel folic acid (FA)-conjugated amphiphilic block
      copolymers of polyethylene glycol (PEG) and poly-beta-benzyl-L-aspartate (PBLA)
      with the potential to act as pH-responsive drug release reservoirs were
      synthesized. The photosensitizer, 2,4-diacetyl deuteroporphyrin IX dimethyl ether
      (DD-PpIX), was conjugated to the copolymers through pH-sensitive hydrazone
      linkage. The syntheses and compositions of all copolymers were confirmed by 1H
      NMR measurement. Photosensitizer-conjugated amphiphilic copolymeric nanoparticles
      (FA-PEG-P(Asp-Hyd)-DD-PpIX) were prepared by micelle formation in aqueous
      solution. The particle sizes of the FA-PEG-PBLA and FA-PEG-P(Asp-Hyd)-DD-PpIX
      nanoparticles were determined by light-scattering measurements. The range was 105
      298 nm, depending on copolymer molecular weight and composition. Field emission
      scanning electron microscopy showed that the FA-PEG-P(Asp-Hyd)-DD-PpIX
      copolymeric nanoparticles were submicron in size and spherical in shape. The
      results of in vitro release tests showed that the release profiles of DD-PpIX
      from the nanoparticles were strongly pH-dependent and influenced by the amount of
      photosensitizer that was conjugated. In vitro tests using HeLa cells indicated
      that the FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticles had low dark-toxicity and showed
      more than 97% of cellular uptake. Based on our results, the FA-PEG-P(Asp-Hyd)-DD
      PpIX nanoparticle system could be a promising approach for developing novel
      photosensitizer delivery carriers for photodynamic therapy.

PMID- 22983022
TI  - CHADS(2) and CHA(2)DS (2)-VASc score of patients with atrial fibrillation or
      flutter and newly detected left atrial thrombus.
AB  - BACKGROUND: The risk of developing a stroke or systemic embolus due to a left
      atrial (LA) thrombus in patients with atrial fibrillation (AF) and/or atrial
      flutter (AFL) is estimated by the CHADS(2) score and more recently the
      CHA(2)DS(2)-VASc score. We aimed to further characterize AF/AFL patients who were
      found to have a LA thrombus on a transesophageal echocardiogram (TEE). METHODS
      AND RESULTS: Of 3,165 TEE between 2005 and 2011 for a broad spectrum of
      indications, we detected 65 AF patients with LA thrombus (2 %). There were 40 men
      and 25 women, mean age was 65 +/- 13 years (range 36-88 years). Mean CHADS(2)
      score was 1.8 +/- 1.1 and mean CHA(2)DS(2)-VASc score was 3.0 +/- 1.6. 11
      patients (17 %) had a CHADS(2) score of 0, 12 patients (18 %) of 1, 28 patients
      (43 %) of 2 and 12 patients (18 %) of 3. Hypertension was the most frequent risk
      factor (72 %), followed by congestive heart failure (32 %), diabetes (23 %) and
      age >=75 years (23 %). Mean difference between CHADS(2) and CHA(2)DS(2)-VASc was
      1.25 +/- 0.91. Of the 11 patients (17 %) with a LA thrombus despite a CHADS(2)
      score of 0, five had a CHA(2)DS(2)-VASc score of 0, four a CHA(2)DS(2)-VASc score
      of 1 and two a CHA(2)DS(2)-VASc score of 2. CONCLUSION: In an unselected TEE
      population with newly detected LA thrombus about one-third of patients fell into
      the low-risk group when classified based on the CHADS(2) score, while a much
      lower population fell in the same low-risk group when classified according to the
      CHA(2)DS(2)-VASc score. However, this does not prove clinical superiority of the
      CHA(2)DS(2)-VASc score over the established CHADS(2) score. Whether our
      observation has clinical implications (e.g. TEE prior to LA ablation irrespective
      of CHADS(2) score), or argues for use of the CHA(2)DS(2)-VASc score needs to be
      evaluated in prospective studies.

PMID- 22983023
TI  - Ductal plate malformation in patients with biliary atresia.
AB  - The presence of ductal plate malformation (DPM+) on liver histology in children
      with biliary atresia (BA) is a marker of early intrauterine disease onset and an
      indication of an unfavorable prognosis. We studied the prognostic value of DPM in
      infants with BA after hepatoportoenterostomy (HPE). We reviewed 28 BA patients
      who underwent HPE in a single medical center. We examined the time of jaundice
      onset after delivery (conjugated hyperbilirubinemia): early onset (fetal
      phenotype with no jaundice-free interval) vs. late onset (perinatal phenotype
      with jaundice-free interval) and the presence or absence of DPM (DPM+ or DPM-)
      histopathology. Primary outcome was jaundice clearance at 3 months after HPE and
      survival with native liver (SNL). Eight children had fetal and 20 had perinatal
      BA (8 DPM+, 12 DPM-). At 3 months after HPE, no patients with fetal BA had
      achieved jaundice clearance, while jaundice clearance was achieved in five
      patients with DPM+ perinatal disease and four patients with DPM- perinatal BA (P
      = 0.03, comparing all three groups; P = 0.36, comparing DPM+ vs. DPM- perinatal
      patients). Median SNL was 8.6 months for fetal BA patients, 148.2 months for DPM+
      perinatal BA patients, and 93.2 months for DPM- perinatal BA patients (log-rank
      test, P < 0.001, comparing all three groups; P = 0.59, comparing DPM+ vs. DPM-
      perinatal patients). After adjusting for BA type, age older than 2 months at HPE
      was associated with worse SNL [P = 0.03; hazard ratio = 4.0 (95 % CI, 1.1-14.2)].
      CONCLUSIONS: Early onset of jaundice, regardless of DPM histology, was the most
      ominous sign of poor outcome in infants with BA after HPE.

PMID- 22983024
TI  - The etiology of small and fresh rectal bleeding in not-sick neonates: should we
      initially suspect food protein-induced proctocolitis?
AB  - This study was performed to identify the cause and frequency of food protein
      induced proctocolitis (FPIPC) in not-sick neonates with small and fresh rectal
      bleeding and to verify the effectiveness of oral food elimination and challenge
      test (ECT) as a diagnostic method of FPIPC. We prospectively analyzed neonates
      with small and fresh rectal bleeding who were clinically normal. We investigated
      age at symptom onset, feeding at onset of bleeding, the time of bleeding
      disappearance, stool smear and culture, endoscopic findings, and histopathologies
      in the biopsy specimens of 16 not-sick neonates. We performed food ECT in cases
      with over 4 days of persistent rectal bleeding in the absence of any other
      etiology. In 16 not-sick neonates with rectal bleeding, the median age at symptom
      onset was 8.5 (1-43) days. Endoscopic abnormalities were observed in all 16
      patients, and in 10 cases satisfying the pathological guidelines for FPIPC, two
      (12.5 %) were confirmed as FPIPC by food ECT. In the other 14 (87.5 %) cases,
      rectal bleeding spontaneously disappeared after on average at 4 (1-8) days and
      thus was diagnosed as idiopathic neonatal transient colitis (INTC). CONCLUSIONS:
      FPIPC is rare as a cause of small and fresh rectal bleeding in not-sick newborns
      and most of cases proved to be INTC. Although clinical findings are suspected as
      its symptoms and histological results satisfy its diagnostic criteria, FPIPC
      should be carefully confirmed through food ECT.

PMID- 22983025
TI  - The socioeconomic and biological risk factors for developmental delay in early
      childhood.
AB  - To investigate the biological and socioeconomic factors associated with
      developmental attainment in socioeconomically disadvantaged children. This study
      was performed at the Dr. Sami Ulus Children's Health and Diseases Training and
      Research Hospital, between January and December 2010. The effects of biological,
      socioeconomic risk factors on developmental delay were investigated in 692
      children (3 months-5 years) using the Denver II. Low-level maternal education
      (odds ratio [OR], 11.118; 95 % CI, 4.211-29.351), low-level paternal education
      (OR, 2.107; 95 % CI, 1.333-3.331), low-level household income (OR, 2.673; 95 %
      CI, 1.098-2.549), and >= 3 children in the family (OR, 1.871; 95 % CI, 1.206
      2.903) were strongly associated with abnormal on Denver II; biological risk
      factors, including birth weight, gestational age at birth, and maternal age at
      birth <20 years, were correlated with suspect on Denver II results based on
      univariate analysis. Low-level maternal education (OR, 6.281; 95 % CI, 2.193
      17.989), premature birth (32-36 weeks of gestation; OR, 0.535; 95 % CI, 0.290
      0.989) were strongly associated with abnormal on Denver II results, and low-level
      paternal education (OR, 3.088; 95 % CI, 1.521-6.268), low-level household income
      (OR, 1.813; 95 % CI, 1.069-3.077), low birth weight (<1,500 g; OR, 3.003; 95 %
      CI, 1.316-6.854), premature birth (27-31 weeks of gestation; OR, 2.612; 95 % CI,
      1.086-6.286), and maternal age at birth <20 years (OR, 3.518; 95 % CI, 1.173
      10.547) were strongly associated with suspect on Denver II results based on
      multivariate analysis. CONCLUSION: Socioeconomic risk factors were observed to be
      as important as biological risk factors in the development of children aged 3
      months-5 years.

PMID- 22983026
TI  - Accelerometry-assessed sedentary behaviour and physical activity levels during
      the segmented school day in 10-14-year-old children: the HAPPY study.
AB  - The school day offers several different time periods that provide varying
      opportunities for sedentary time (SED) and engagement in physical activity (PA),
      yet little is known about the PA and sedentary behaviour patterns of boys and
      girls during these times. The volume, intensity and temporal distributions of SED
      and PA undertaken by 135 schoolchildren aged 10-14 years, during different
      segments of the school day: (a) school transport, (b) morning recess, (c) lunch
      break, (d) class time and (e) after school, were explored using triaxial
      accelerometry. PA was categorised into SED, light PA (LPA), moderate PA (MPA) and
      vigorous PA (VPA). Girls engaged in significantly more SED and LPA than boys
      during recess and lunch break (p < 0.05), while boys engaged in significantly
      higher levels of VPA during recess (p < 0.001) and MPA and VPA during lunch break
      (p < 0.001). PA engagement was similar between sexes during other segments of the
      day. CONCLUSION: PA patterns appear more beneficial for health in boys during
      less structured school-based time periods and interventions may therefore target
      opportunities for girls to be physically active during these times to overcome
      this observed sex deficit.

PMID- 22983028
TI  - Biological bulletin virtual symposium: discoveries in animal symbiosis in the
      "omics" age.

PMID- 22983029
TI  - Investigating bacterial-animal symbioses with light sheet microscopy.
AB  - Microbial colonization of the digestive tract is a crucial event in vertebrate
      development, required for maturation of host immunity and establishment of normal
      digestive physiology. Advances in genomic, proteomic, and metabolomic
      technologies are providing a more detailed picture of the constituents of the
      intestinal habitat, but these approaches lack the spatial and temporal resolution
      needed to characterize the assembly and dynamics of microbial communities in this
      complex environment. We report the use of light sheet microscopy to provide high
      resolution imaging of bacterial colonization of the intestine of Danio rerio, the
      zebrafish. The method allows us to characterize bacterial population dynamics
      across the entire organ and the behaviors of individual bacterial and host cells
      throughout the colonization process. The large four-dimensional data sets
      generated by these imaging approaches require new strategies for image analysis.
      When integrated with other "omics" data sets, information about the spatial and
      temporal dynamics of microbial cells within the vertebrate intestine will provide
      new mechanistic insights into how microbial communities assemble and function
      within hosts.

PMID- 22983030
TI  - Making the most of "omics" for symbiosis research.
AB  - Omics, including genomics, proteomics, and metabolomics, enable us to explain
      symbioses in terms of the underlying molecules and their interactions. The
      central task is to transform molecular catalogs of genes, metabolites, etc., into
      a dynamic understanding of symbiosis function. We review four exemplars of omics
      studies that achieve this goal, through defined biological questions relating to
      metabolic integration and regulation of animal-microbial symbioses, the genetic
      autonomy of bacterial symbionts, and symbiotic protection of animal hosts from
      pathogens. As omic datasets become increasingly complex, computationally
      sophisticated downstream analyses are essential to reveal interactions not
      evident from visual inspection of the data. We discuss two approaches,
      phylogenomics and transcriptional clustering, that can divide the primary output
      of omics studies-long lists of factors-into manageable subsets, and we describe
      how they have been applied to analyze large datasets and generate testable
      hypotheses.

PMID- 22983031
TI  - Exploring symbioses by single-cell genomics.
AB  - Single-cell genomics has advanced the field of microbiology from the analysis of
      microbial metagenomes where information is "drowning in a sea of sequences," to
      recognizing each microbial cell as a separate and unique entity. Single-cell
      genomics employs Phi29 polymerase-mediated whole-genome amplification to yield
      microgram-range genomic DNA from single microbial cells. This method has now been
      applied to a handful of symbiotic systems, including bacterial symbionts of
      marine sponges, insects (grasshoppers, termites), and vertebrates (mouse, human).
      In each case, novel insights were obtained into the functional genomic repertoire
      of the bacterial partner, which, in turn, led to an improved understanding of the
      corresponding host. Single-cell genomics is particularly valuable when dealing
      with uncultivated microorganisms, as is still the case for many bacterial
      symbionts. In this review, we explore the power of single-cell genomics for
      symbiosis research and highlight recent insights into the symbiotic systems that
      were obtained by this approach.

PMID- 22983032
TI  - Study of cnidarian-algal symbiosis in the "omics" age.
AB  - The symbiotic associations between cnidarians and dinoflagellate algae
      (Symbiodinium) support productive and diverse ecosystems in coral reefs. Many
      aspects of this association, including the mechanistic basis of host-symbiont
      recognition and metabolic interaction, remain poorly understood. The first
      completed genome sequence for a symbiotic anthozoan is now available (the coral
      Acropora digitifera), and extensive expressed sequence tag resources are
      available for a variety of other symbiotic corals and anemones. These resources
      make it possible to profile gene expression, protein abundance, and protein
      localization associated with the symbiotic state. Here we review the history of
      "omics" studies of cnidarian-algal symbiosis and the current availability of
      sequence resources for corals and anemones, identifying genes putatively involved
      in symbiosis across 10 anthozoan species. The public availability of candidate
      symbiosis-associated genes leaves the field of cnidarian-algal symbiosis poised
      for in-depth comparative studies of sequence diversity and gene expression and
      for targeted functional studies of genes associated with symbiosis. Reviewing the
      progress to date suggests directions for future investigations of cnidarian-algal
      symbiosis that include (i) sequencing of Symbiodinium, (ii) proteomic analysis of
      the symbiosome membrane complex, (iii) glycomic analysis of Symbiodinium cell
      surfaces, and (iv) expression profiling of the gastrodermal cells hosting
      Symbiodinium.

PMID- 22983033
TI  - Multi-partner interactions in corals in the face of climate change.
AB  - Recent research has explored the possibility that increased sea-surface
      temperatures and decreasing pH (ocean acidification) contribute to the ongoing
      decline of coral reef ecosystems. Within corals, a diverse microbiome exerts
      significant influence on biogeochemical and ecological processes, including food
      webs, organismal life cycles, and chemical and nutrient cycling. Microbes on
      coral reefs play a critical role in regulating larval recruitment, bacterial
      colonization, and pathogen abundance under ambient conditions, ultimately
      governing the overall resilience of coral reef systems. As a result, microbial
      processes may be involved in reef ecosystem-level responses to climate change.
      Developments of new molecular technologies, in addition to multidisciplinary
      collaborative research on coral reefs, have led to the rapid advancement in our
      understanding of bacterially mediated reef responses to environmental change.
      Here we review new discoveries regarding (1) the onset of coral-bacterial
      associations; (2) the functional roles that bacteria play in healthy corals; and
      (3) how bacteria influence coral reef response to environmental change, leading
      to a model describing how reef microbiota direct ecosystem-level response to a
      changing global climate.

PMID- 22983034
TI  - What hydra has to say about the role and origin of symbiotic interactions.
AB  - The Hydra holobiont involves at least three types of organisms that all share a
      long coevolutionary history and appear to depend on each other. Here I review how
      symbiotic algae and stably associated bacteria interact with the Hydra host and
      where in the tissue they are located. In particular I discuss the role of Toll
      like receptor (TLR) signaling in maintaining Hydra's species-specific microbiota.
      I also discuss studies in Hydra viridis and its symbiotic Chlorella algae which
      indicate that the symbiotic algae are critically involved in the control of
      sexual differentiation in green Hydra. Finally, I review the state of "omics" in
      this tripartite association and the fact that the functioning of this holobiont
      is also a tale of several genomes.

PMID- 22983036
TI  - Host/microbe interactions revealed through "omics" in the symbiosis between the
      Hawaiian bobtail squid Euprymna scolopes and the bioluminescent bacterium Vibrio
      fischeri.
AB  - The association between Euprymna scolopes, the Hawaiian bobtail squid, and Vibrio
      fischeri, a bioluminescent bacterium, has served as a model for beneficial
      symbioses for over 25 years. The experimental tractability of this association
      has helped researchers characterize many of the colonization events necessary for
      symbiosis. Recent technological advances, such as the sequenced genome of V.
      fischeri, DNA microarrays, and high-throughput transcriptomics and proteomics,
      have allowed for the identification of host and symbiont factors that are
      important in establishing and maintaining specificity in the association. We
      highlight some of these findings pertaining to quorum sensing, luminescence,
      responses to reactive oxygen and nitrogen species, recognition of microbe
      associated molecular patterns by the innate immune system of the host, and a diel
      rhythm that helps regulate the symbiont population. We also discuss how
      comparative genomics has allowed the identification of symbiont factors important
      for specificity and why sequencing the host's genome should be a priority for the
      research community.

PMID- 22983035
TI  - Nematode-bacterium symbioses--cooperation and conflict revealed in the "omics"
      age.
AB  - Nematodes are ubiquitous organisms that have a significant global impact on
      ecosystems, economies, agriculture, and human health. The applied importance of
      nematodes and the experimental tractability of many species have promoted their
      use as models in various research areas, including developmental biology,
      evolutionary biology, ecology, and animal-bacterium interactions. Nematodes are
      particularly well suited for the investigation of host associations with bacteria
      because all nematodes have interacted with bacteria during their evolutionary
      history and engage in a variety of association types. Interactions between
      nematodes and bacteria can be positive (mutualistic) or negative
      (pathogenic/parasitic) and may be transient or stably maintained (symbiotic).
      Furthermore, since many mechanistic aspects of nematode-bacterium interactions
      are conserved, their study can provide broader insights into other types of
      associations, including those relevant to human diseases. Recently, genome-scale
      studies have been applied to diverse nematode-bacterial interactions and have
      helped reveal mechanisms of communication and exchange between the associated
      partners. In addition to providing specific information about the system under
      investigation, these studies also have helped inform our understanding of genome
      evolution, mutualism, and innate immunity. In this review we discuss the
      importance and diversity of nematodes, "omics"' studies in nematode-bacterial
      systems, and the wider implications of the findings.

PMID- 22983038
TI  - Origins and evolutionary flexibility of chemosynthetic symbionts from deep-sea
      animals.
AB  - Bathymodiolin mussels dominate hydrothermal vent and cold seep communities
      worldwide. Symbiotic associations with chemosynthetic sulfur- and methane
      oxidizing bacteria that provide for their nutrition are the key to their
      ecological and evolutionary success. The current paradigm is that these symbioses
      evolved from two free-living ancestors, one methane-oxidizing and one sulfur
      oxidizing bacterium. In contrast to previous studies, our phylogenetic analyses
      of the bathymodiolin symbionts show that both the sulfur and the methane
      oxidizers fall into multiple clades interspersed with free-living bacteria, many
      of which were discovered recently in metagenomes from marine oxygen minimum
      zones. We therefore hypothesize that symbioses between bathymodiolin mussels and
      free-living sulfur- and methane-oxidizing bacteria evolved multiple times in
      convergent evolution. Furthermore, by 16S rRNA sequencing and fluorescence in
      situ hybridization, we show that close relatives of the bathymodiolin symbionts
      occur on hosts belonging to different animal phyla: Raricirrus beryli, a
      terebellid polychaete from a whale-fall, and a poecilosclerid sponge from a cold
      seep. The host range within the bathymodiolin symbionts is therefore greater than
      previously recognized, confirming the remarkable flexibility of these symbiotic
      associations.

PMID- 22983037
TI  - Strategies of genomic integration within insect-bacterial mutualisms.
AB  - Insects, the most diverse group of macroorganisms with 900,000 known species,
      have been a rich playground for the evolution of symbiotic associations.
      Symbionts of this enormous animal group include a range of microbial partners.
      Insects are prone to establishing relationships with intracellular bacteria,
      which include the most intimate, highly integrated mutualisms known in the
      biological world. In recent years, an explosion of genomic studies has offered
      new insights into the molecular, functional, and evolutionary consequences of
      these insect-bacterial partnerships. In this review, I highlight some insights
      from genome sequences of bacterial endosymbionts and select insect hosts.
      Notably, comparisons between facultative and obligate bacterial mutualists have
      revealed distinct genome features representing different stages along a shared
      trajectory of genome reduction. Bacteria associated with the cedar aphid offer a
      snapshot of a transition from facultative to obligate mutualism, illustrating the
      genomic basis of this key step along the symbiotic spectrum. In addition, genomes
      of stable, dual bacterial symbionts reflect independent instances of astonishing
      metabolic integration. In these systems, synthesis of key nutrients, and perhaps
      basic cellular processes, require collaboration among co-residing bacteria and
      their insect host. These findings provide a launching point for a new era of
      genomic explorations of bacterial-animal symbioses. Future studies promise to
      reveal symbiotic strategies across a broad ecological and phylogenetic range, to
      clarify key transitions along a spectrum of interaction types, and to fuel new
      experimental approaches to dissect the mechanistic basis of intimate host
      symbiont associations.

PMID- 22983039
TI  - 16S rDNA-based metagenomic analysis of bacterial diversity associated with two
      populations of the kleptoplastic sea slug Elysia chlorotica and its algal prey
      Vaucheria litorea.
AB  - The molluscan sea slug Elysia chlorotica is best known for its obligate
      endosymbiosis with chloroplasts (= kleptoplasty) from its algal prey Vaucheria
      litorea and its ability to sustain itself photoautotrophically for several
      months. This unusual photosynthetic sea slug also harbors an array of undescribed
      bacteria, which may contribute to the long-term success of the symbiosis. Here,
      we utilized 16S rDNA-based metagenomic analyses to characterize the microbial
      diversity associated with two populations of E. chlorotica from Halifax, Nova
      Scotia, Canada, and from Martha's Vineyard, Massachusetts, USA. Animals were
      examined immediately after collection from their native environments, after being
      starved of their algal prey for several months, and after being bred in the
      laboratory (second-generation sea slugs) to characterize the effect of varying
      environmental and culturing conditions on the associated bacteria. Additionally,
      the microbiome of the algal prey, laboratory-cultured V. litorea, was analyzed to
      determine whether the laboratory-bred sea slugs obtained bacteria from their
      algal food source during development. Bacterial profiles varied between
      populations and among all conditions except for the F2 laboratory-bred samples,
      which were similar in diversity and abundance, but not to the algal microbiome.
      Alpha-, beta-, and gamma-proteobacteria dominated all of the samples along with
      Actinobacteria, Bacilli, Flavobacteria, and Sphingobacteria. Bacteria capable of
      polysaccharide digestion and photosynthesis, as well as putative nitrogen
      fixation, vitamin B(12) production, and natural product biosynthesis were
      associated with the sea slug and algal samples.

PMID- 22983040
TI  - Investigation into the physiologies of Aeromonas veronii in vitro and inside the
      digestive tract of the medicinal leech using RNA-seq.
AB  - Host-associated microbial communities are widespread in nature and vital to the
      health and fitness of the host. Deciphering the physiology of the microbiome in
      vivo is critical to understanding the molecular basis of the symbiosis. Recently,
      the development and application of high-throughput sequencing techniques,
      particularly RNA-seq, for studying microbial communities has enabled researchers
      to address not only which microbes are present in a given community but also how
      the community functions. For microbes that can also be cultivated in the
      laboratory, RNA-seq provides the opportunity to identify genes that are
      differentially expressed during symbiosis by comparing in vitro to in vivo
      transcriptomes. In the current study, we used RNA-seq to identify genes expressed
      by the digestive-tract microbiome of the medicinal leech, Hirudo verbana, and by
      one of the two dominant symbionts, Aeromonas veronii, in a rich medium. We used a
      comparative approach to identify genes differentially expressed during symbiosis
      and gain insight into the symbiont's physiology in vivo. Notable findings include
      evidence for the symbionts experiencing environmental stress, performing arginine
      catabolism, and expressing noncoding RNAs that are implicated in stationary phase
      survival, a state in which A. veronii persists for months within the host.

PMID- 22983060
TI  - Limited featured-based attention to multiple features.
AB  - Attending to a feature (e.g., color or motion direction) can enhance the early
      visual processing of that feature. However, it is not known whether one can
      simultaneously enhance multiple features. We examined people's ability to attend
      to multiple features in a feature cueing paradigm. Each trial contained two
      intervals consisting of a random dot motion stimulus. One interval (noise) had 0%
      coherence (no net motion), while the other interval (signal) moved in a
      particular direction with varying levels of coherence. Participants reported
      which interval contained the signal in one of three cueing conditions. In the one
      cue condition, a line segment preceded the stimuli indicating the direction of
      the signal with 100% validity. In the two-cue condition, two lines preceded the
      stimuli, indicating the signal would move in one of the two cued directions. In
      the no-cue condition, no line segment appeared before the dot stimuli. In several
      experiments, we consistently observed a lower detection threshold in the one-cue
      condition than the no-cue condition, showing that participants can enhance
      processing of a single feature. However, detection threshold was consistently
      higher for the two-cue than one-cue condition, indicating that participants could
      not simultaneously enhance two motion directions as effectively as one direction.
      This finding revealed a severe capacity limit in our ability to enhance early
      visual processing for multiple features.

PMID- 22983061
TI  - Evaluation of candidate biomarkers to predict cancer cell sensitivity or
      resistance to PARP-1 inhibitor treatment.
AB  - Impaired DNA damage response pathways may create vulnerabilities of cancer cells
      that can be exploited therapeutically. One such selective vulnerability is the
      sensitivity of BRCA1- or BRCA2-defective tumors (hence defective in DNA repair by
      homologous recombination, HR) to inhibitors of the poly(ADP-ribose) polymerase-1
      (PARP-1), an enzyme critical for repair pathways alternative to HR. While
      promising, treatment with PARP-1 inhibitors (PARP-1i) faces some hurdles,
      including (1) acquired resistance, (2) search for other sensitizing, non-BRCA1/2
      cancer defects and (3) lack of biomarkers to predict response to PARP-1i. Here we
      addressed these issues using PARP-1i on 20 human cell lines from carcinomas of
      the breast, prostate, colon, pancreas and ovary. Aberrations of the Mre11-Rad50
      Nbs1 (MRN) complex sensitized cancer cells to PARP-1i, while p53 status was less
      predictive, even in response to PARP-1i combinations with camptothecin or
      ionizing radiation. Furthermore, monitoring PARsylation and Rad51 foci formation
      as surrogate markers for PARP activity and HR, respectively, supported their
      candidacy for biomarkers of PARP-1i responses. As to resistance mechanisms, we
      confirmed the role of the multidrug resistance efflux transporters and its
      reversibility. More importantly, we demonstrated that shRNA lentivirus-mediated
      depletion of 53BP1 in human BRCA1-mutant breast cancer cells increased their
      resistance to PARP-1i. Given the preferential loss of 53BP1 in BRCA-defective and
      triple-negative breast carcinomas, our findings warrant assessment of 53BP1 among
      candidate predictive biomarkers of response to PARPi. Overall, this study helps
      characterize genetic and functional determinants of cellular responses to PARP-1i
      and contributes to the search for biomarkers to exploit PARP inhibitors in cancer
      therapy.

PMID- 22983062
TI  - Quantifying the CDK inhibitor VMY-1-103's activity and tissue levels in an in
      vivo tumor model by LC-MS/MS and by MRI.
AB  - The development of new small molecule-based therapeutic drugs requires accurate
      quantification of drug bioavailability, biological activity and treatment
      efficacy. Rapidly measuring these endpoints is often hampered by the lack of
      efficient assay platforms with high sensitivity and specificity. Using an in vivo
      model system, we report a simple and sensitive liquid chromatography-tandem mass
      spectrometry assay to quantify the bioavailability of a recently developed novel
      cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose
      biological activity is enhanced via dansylation. We developed a rapid organic
      phase extraction technique and validated wide and functional VMY-1-103
      distribution in various mouse tissues, consistent with its enhanced potency
      previously observed in a variety of human cancer cell lines. More importantly, in
      vivo MRI and single voxel proton MR-Spectroscopy further established that VMY-1
      103 inhibited disease progression and affected key metabolites in a mouse model
      of hedgehog-driven medulloblastoma.

PMID- 22983064
TI  - Correlation between salivary urea level and dental caries.
AB  - OBJECTIVES: The aim of this study was to determine the values of salivary urea in
      subjects with different caries activity. MATERIAL AND METHOD: The planned trials
      were conducted in 80 children of both sexes, aged 16 years, with different caries
      activity. Based on the condition of teeth, the DMFT-index, respondents were
      divided into two groups: the first group consisted of 40 examinees with a low to
      very low index of caries (0-3), the second group consisted of 40 examinees with a
      high index of caries (>10). Material for biochemical testing of the saliva sample
      was taken from all subjects at different time intervals: 5, 30 and 60 minutes
      from the (daily) meal. The examined parameters were followed in the same
      examinees in a sample of saliva taken in the morning before consuming any food or
      implementation of oral hygiene: they represent basic information compared with
      the results of the examination. The concentration of urea in saliva was
      determined by the enzyme method of continuous measurement. This method is based
      on the principle of hydrolysis of urea, using the enzyme urease. RESULTS:
      Salivary concentration of urea, measured fasting in the morning (basic values) in
      examinees with a low caries index, ranging in limits from 5.50 to 9.10 mmol/l,
      and significantly lower values in examines with a high DMFT-index (from 3.40 to
      5.50 mmol/l). The same was done with the concentration of salivary urea at
      different time intervals after taking the meal - 5, 30 and 60 minutes in the
      examinees with a different DMFT-index. With the increasing time interval after
      taking a meal, the concentration of salivary urea continuously and significantly
      declines compared to its baseline concentration. The largest decrease of
      concentration of urea in terms of its basic value in all examinees with a
      different DMFT-index (with low and high) took place during the 60 minutes after
      having the meal. CONCLUSION: Saliva with its constituents plays an important role
      in maintaining oral, and exspecially dental health. Urea contributes in
      maintaining the acidobasic balance of saliva, and thus affects the incidence of
      caries. The positive effect of urea was confirmed by the values found in this
      study: the respondents with a lower DMFT-index present a higher concentration of
      urea than in the basic values, and in the values of stimulated (through the meal)
      saliva, followed in all intervals.

PMID- 22983063
TI  - dj-1beta regulates oxidative stress, insulin-like signaling and development in
      Drosophila melanogaster.
AB  - DJ-1 (or PARK-7) is a multifunctional protein implicated in numerous pathologies
      including cancer, sterility and Parkinson disease (PD). The popular genetic model
      Drosophila melanogaster has two orthologs, dj-1: alpha and beta. Dysfunction of
      dj-1beta strongly impairs fly mobility in an age-dependent manner. In this study,
      we analyze in detail the molecular mechanism underlying the dj-1beta mutant
      phenotype. Mitochondrial hydrogen peroxide production, but not superoxide
      production, was increased in mutant flies. An increase in peroxide leak from
      mitochondria causes oxidative damage elsewhere and explains the strong reduction
      in mobility caused by dj-1beta mutation. However, at the same time, increased
      levels of hydrogen peroxide activated a pro-survival program characterized by (1)
      an alteration in insulin-like signaling, (2) an increase in mitochondrial
      biogenesis and (3) an increase in the de-acetylase activity of sirtuins. The
      activation of this pro-survival program was associated with increased longevity
      under conditions of moderate oxidative stress. Additionally, the dj-1beta
      mutation unexpectedly accelerated development, a phenotype not previously
      associated with this mutation. Our results reveal an important role of dj-1beta
      in oxidative stress handling, insulin-like signaling and development in
      Drosophila melanogaster.

PMID- 22983065
TI  - Effectiveness of erlotinib as a second line therapy for patients with epidermal
      growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC): our
      clinical experience.
AB  - PURPOSE: The aim of this study was to evaluate tumour response, QoL and adverse
      effects of erlotinib, EGFR tyrosine kinase inhibitor (TKI), as a second line
      therapy for patients with EGFR mutation in NSCLC, after failure of previous first
      line therapy. METHODS: During the year 2010-11, 5 patients were enrolled in this
      study for testing EGFR mutations, after conditions for testing were created in
      Macedonia. We screened 5 patients for EGFR mutations by direct sequencing of
      exons 18 to 21, by retrospective analysis of their previous biopsy samples. Three
      of the patients were men and two of the patients were women. Two of the males
      were former smokers and one male and both females had never smoked. All the
      patients who were enrolled in the study had histologically proven
      adenocarcionoma. the patients started with erlotinib 150 mg, one tablet per day,
      after failure on previous first-line platinum-based chemotherapy, with or without
      surgery and radiotherapy. Assessment of tumour response was according to RECIST
      criteria at the follow-up visits every 4 weeks. We analysed tumour response from
      the beginning with erlotinib until tumuor progression or detection of severe
      toxicity. Assessment was performed only for those patients with EGFR mutations.
      Assessment of QoL was performed by patients' subjective answers, as subjective
      improvement and without subjective improvements. Adverse effects were applied
      according to WHO criteria. RESULTS: Tissue was available for all 5 cases, two
      (40%) of which were found to harbour an EGFR mutation, identified as exon 19
      deletions. Two patients responded to therapy. A complete response was seen in a
      female patient for 37 months. Progressive disease was the reason for stopping
      erlotinib after 37 months and starting third-line therapy. A partial response in
      one male patient was assessed for 30 months and is still in follow up. This
      patient is still alive and in good condition. The two patients reported
      subjective improvements during treatment with erlotinib. Skin rash was grade 2-3,
      and diarrhoea was grade 1-2. Both patients complained of hair loss, but without
      complete alopecia. CONCLUSIONS: Considering our clinical results, we recommend
      target therapy with erlotinib for patients with NSCLC and EGFR mutations as a
      second-line treatment. Our excellent results encouraged us to require prospective
      tissue procurement for all patients in Macedonia. This may in fact require a
      shift in diagnostic practice, from the current emphasis on fine-needle
      aspiration, which often provides insufficient material for molecular analysis, to
      obtaining more substantial biopsies and to provide this treatment as first-line
      for selected patients.

PMID- 22983066
TI  - Seizures after use and abuse of tramadol.
AB  - Seizures have been reported with tramadol monotherapy in animal and human
      studies, both at recommended and high doses. After tramadol abuse or overdose,
      neurotoxicity is speculated to be related to the reuptake inhibition of serotonin
      and norepinephrine, rather than its opioid effects. THE AIM OF THIS STUDY is to
      show three unusual cases of seizures provoked by tramadol. CASE REPORTS: A 56
      year-old female was hospitalized with intensive lumbosacral pain. Because the
      standard therapy with non steroid anti-inflammatory drugs and diazepam did not
      show enough pain release, Tramadol ampoules were applied. Fifteen minutes later
      generalized tonic clonic seizure was noticed. A 24 year-old female was admitted
      to the Toxicology Clinic, one hour after ingestion of 1000 mg Tramadol (20 pills
      of 50 mg) in a suicide attempt. Five hours later generalized tonic clonic seizure
      was noticed. A 27 year-old male was hospitalized for detoxification procedure
      with buprenorphine. The patient was a more than four years heroin abuser, and in
      the last two years he mixed the heroin with high doses of tramadol. 16 hours
      later, after application of the first 2 mg of Buprenorphine, generalized tonic
      clonic seizure was noticed. CONCLUSION: Tramadol prescription, use and abuse are
      connected with the risk of developing seizures. The neurotoxicity of tramadol
      commonly manifests as seizures.

PMID- 22983067
TI  - Contributions of doctors from Serbia to the establishment and initial development
      of the Faculty of Medicine in Skopje,  Republic of Macedonia.
AB  - AIM: To analyse and present the milestone activities and actors, with special
      emphasis on the contribution of doctors from Serbia to the establishment and
      initial development of the Faculty of Medicine in Skopje, Macedonia, in the
      period 1947-60 and beyond. METHOD: A retrospective study based on archive
      materials, encyclopedias and jubilee publications of the Faculty of Medicine and
      Faculty of Dentistry in Skopje, other relevant sources of information, and a
      review of the relevant literature. RESULTS: The Faculty of Medicine in Skopje was
      founded in 1947 and the first meeting of the Teachers' Council of the Faculty was
      held on March 17, 1947. The first generation of 153 students was enrolled in the
      autumn of 1947 and the first lecture was delivered on November 3, 1947. More than
      20 doctors from Serbia, half of them faculty staff, had joined the initiative of
      the Government of Macedonia for establishing the Faculty of Medicine in Skopje in
      1947. They played leading roles in creating a number of the faculty
      departments/chairs, establishing 6 institutes and 6 clinics within the newly
      established Faculty of Medicine in Skopje in 1947 and in the first 10-15 years of
      its development. CONCLUSION: The Faculty of Medicine in Skopje, founded in 1947,
      played a crucial role in the education of medical professionals, in improving the
      poor health status of the population and the overall further development of the
      health system and provision of health care to the population of Macedonia. The
      contribution of the doctors from Serbia to the establishment and initial
      development of the Faculty of Medicine in Skopje, during the period 1947-1960 and
      beyond, was remarkable and important.

PMID- 22983068
TI  - First scientific meeting of Yugoslav nephrologists, Struga, Republic of
      Macedonia, 26-28.IX 1977--introduction to the development of nephrology--in
      former Yugoslavia.
AB  - The first scientific meeting of nephrologists in Yugoslavia with international
      participation was held in Struga, Republic of Macedonia, on Lake Ohrid, 26 to 28
      September 1977. During the Third Symposium on Endemic Nephropathy, which was held
      in Nis on 5 to 8 November 1975 at the Radon Hotel, representatives of the
      nephrology sections of the republics founded the Yugoslav Society of Nephrology.
      Academician Vojislav Danilovic from Belgrade was elected as the Association's
      first President. It was decided that the first scientific meeting of Yugoslav
      Nephrologists be held in Struga, Macedonia, 1977, and the first Nephrology
      Congress in Belgrade in 1979. It was also agreed that congresses be held every
      four years, and to organize scientific meetings between congresses. In this way,
      the Nephrology Association of Yugoslavia gained the opportunity for a lot of
      activities every two years. The Proceedings of the First Scientific Meeting of
      Yugoslav Nephrologists contained 6 plenary lectures and 84 papers presented
      during the three sections of the scientific meeting, 31 about hypertension and
      kidneys, 19 about immunology in nephrology and 34 about dialysis. The first
      scientific meeting of Yugoslav nephrologists with international participation was
      the first major review of the achievements of Nephrology in Yugoslavia,
      assessment of its results, work incentives and the creation of a vision for
      future development. The meeting strengthened the ties among the colleagues, new
      acquaintances were created, and new ideas for further cooperation appeared.

PMID- 22983069
TI  - Disseminated subcutaneous phaeohyphomycosis caused by Exophiala oligosperma in a
      patient with Wegener's granulomatosis.

PMID- 22983072
TI  - Good efficacy of artemether-lumefantrine for uncomplicated falciparum malaria in
      eastern Sumba, East Nusatenggara, Indonesia.
AB  - AIM: to evaluate the safety and efficacy of a fixed combination of artemether
      lumefantrine for likely use against failures of the artesunate-amodiaquine first
      line therapy. METHODS: the study was an open label single arm uncontrolled trial.
      we evaluated the safety and efficacy of standard artemether-lumefantrine therapy
      in 59 subjects with uncomplicated malaria caused by Plasmodium falciparum on the
      island of Sumba in eastern Indonesia. No treatment failures occurred up to day
      35. One subject had recurrent parasitemia on day 42 that showed a genotype
      consistent with recrudescence. The efficacy of this therapy was thus estimated to
      be 98.3% (95% confidence interval=95%-100%). Descriptive analysis was done using
      the SPSS 12 computer software. RESULTS: two hundred and thirteen P. falciparum
      patients met the inclusion criteria for in vivo efficacy study, 79 were given
      artemether-lumefantrine and 134 were treated under another protocol with
      artesunate-amodiaquine or sulfadoxine-pyrimethamine. Among 79 eligible subjects,
      59 successfully completed the 42-day test. As expected, the mean PCT was longer
      than the mean FCT, i.e. 1.34 +/- 0.67 (95% CI 1.21-1.47) and 1.05 +/- 0.05 (95%
      CI 0.95-1.15) days, respectively. On day 3 of treatment, both fever and asexual
      stage of P. falciparum disappeared in all subjects. Observation until Day 35
      showed that all of the 59 subjects treated with artemether-lumefantrine were
      cured. CONCLUSION: the findings of this uncontrolled study suggest good safety
      and efficacy of artemether-lumefantrine for treatment of uncomplicated falciparum
      malaria on Sumba Island in the Lesser Sundas archipelago of eastern Indonesia.

PMID- 22983073
TI  - Potential cross-reactivity of severe acute respiratory syndrome-associated
      coronavirus (SARS-CoV) nucleocapsid (N)-based IgG ELISA assay for plasma samples
      from HIV-1 positive intravenous drug users (IDUs).
AB  - AIM: to evaluate the specificity of the SARS-CoV N protein-based IgG ELISA assay
      for detection of immunoglobulin G (IgG) in plasma samples obtained from HIV-1
      positive and HIV-1 negative intravenous drug users (IDUs). METHODS: the SARS-CoV
      N gene was cloned into pQE-80L vector, and the constructs were transformed into
      Escherichia coli BL21. The 6x His-tagged N protein was expressed by inducing the
      bacterial cells with isopropyl-1-thio-D-galactopyranoside (IPTG) and purified by
      Ni-NTA affinity resin. The 6x His-tagged N protein was used as antigen for ELISA
      assay and evaluated for the serum samples from patients with SARS positive and
      the plasma samples from the HIV-1 positive and negative IDUs. RESULTS: all sera
      samples from patients with SARS positive were the ELISA positive (100%
      sensitivity). The ELISA assay yielded no positive results of the total 61 HIV-1
      negative IDU samples (100% specificity) and two positive results of the total 68
      HIV-1 positive IDU samples (97.06% specificity). CONCLUSION: the specificity of
      the SARS-CoV N protein-based IgG ELISA assay for the detection of the SARS-CoV N
      specific IgG in plasma samples from IDUs with HIV-1 positive is, therefore,
      questionable.

PMID- 22983074
TI  - Insulin resistance as one of indicators for metabolic syndrome and its associated
      factors in Indonesian elderly.
AB  - AIM: to obtain factors that are associated with insulin resistance in Indonesian
      elderly. METHODS: a cross sectional study was conducted at the Geriatric
      Outpatient Clinic of Cipto Mangunkusumo Hopital in 172 elderly patients. Data on
      subject characteristics (age and sex), body mass index, total body fat,
      peripheral subcutaneous fat, trunk subcutaneous fat, waist circumference,
      carbohydrate and fiber intake, physical activity, and 25(OH)D concentration were
      collected. Sample size was calculated in accordance with the formula of sample
      size on hypothesis testing for difference of two proportions and hypothesis
      testing for difference of mean of two independent groups. Significance level of
      95% and power of 80% were used. Chi-square analysis and independent t-test were
      performed. Logistic regression analysis was conducted to recognize the most
      affecting variables for insulin resistance. P<0.05 was considered as the
      significance level. RESULTS: we found that the prevalence of insulin resistance
      among elderly in our study was 25%. Bivariate analysis showed that there was a
      significant association of age and body mass index with insulin resistance in
      elderly. There were also significant differences of mean on fat mass, fat mass
      (%), waist circumference, peripheral subcutaneous fat, trunk subcutaneous fat,
      which were significantly higher in insulin-resistance group compared to the non
      insulin resistance group. Results of multivariate analysis demonstrated that only
      several factors were correlated to insulin resistance in elderly, that were
      peripheral subcutaneous fat (OR 1.09; 95% CI 1.05-1.15) and trunk subcutaneous
      fat (OR 0.93; 95% CI 0.87-0.99). CONCLUSION: peripheral subcutaneous fat and
      trunk subcutaneous fat are associated with insulin resistance in elderly.

PMID- 22983075
TI  - Bone marrow involvement by lymphoproliferative disorders post liver
      transplantation: PTLD Int Survey.
AB  - AIM: to analyze cases of BM PTLD in liver transplant recipients to find any
      specific predictor or prognostic factor associated with this disease
      localization. METHODS: a comprehensive search of the existing literature was
      performed, and 173 liver recipients who had developed PTLD in their post
      transplant course from 19 studies were found and enrolled into analysis. 36 of
      the patients were BM PTLD cases and the remaining was used as controls. RESULTS:
      liver transplant recipients with BM PTLD were significantly more likely to
      represent in male patients (p=0.042) and the elderly (p=0.08). BM PTLD was
      significantly more likely to complicate liver allograft (p=0.027) and spleen
      (p=0.013). Histopathological evaluations showed that BM PTLD lesions were more
      likely of monomorphic type (p=0.025). Multi-organ and disseminated PTLD were
      significantly more prevalent among BM PTLD patients (p<0.001, both) The BM PTLD
      group represented relatively lower survival than patients with other
      localizations, although it did not reach significant level (p=0.1). CONCLUSION:
      our findings alert us to use more sensitive methods to find potential
      simultaneous metastatic lesions in the mentioned organs for liver recipients
      developing BM PTLD. Future studies with prospective approaches are needed to
      confirm our findings.

PMID- 22983076
TI  - Test - retest reliability of the Indonesian version of the Overactive Bladder
      Symptom Score (OABSS) and its correlation with standard assessment tools.
AB  - AIM: to evaluate the test-retest reliability of the Indonesian version of OABSS
      and its correlation with other validated assessment tools for OAB. METHODS:
      eligible patients aged 18 years with established OAB were instructed to complete
      3-day micturition diaries and the OABSS, International Prostate Symptom Score
      (IPSS) and Patient Perception of Bladder Condition (PPBC) on two separate visits:
      Week 0 and Week 2. Test-retest reliability was examined using the internal
      correlation coefficient (ICC) and weighted Kappa coefficients between first and
      second applications of the OABSS. Pearson or Spearman correlation coefficients
      were calculated to test the correlation of OABSS with IPSS, IPSS Quality of Life
      (QOL) item, PPBC and clinical variables of the 3-day voiding diary. RESULTS: ICC
      for the OABSS total score was 0.83. The weighted Kappa coefficients of individual
      scores in OABSS were 0.55-0.66. In the first and second applications of OABSS,
      the Pearson correlation coefficients were 0.46-0.56 and 0.36-0.53 between OABSS
      and three clinical variables of the 3-day voiding diary (frequencies of
      micturition, urgency and urge incontinence). At Visit 1, the Spearman correlation
      coefficients were 0.41 between OABSS and IPSS total score, 0.47 between OABSS and
      IPSS QOL, and 0.34 between OABSS and PPBC. At Visit 2, the Spearman correlation
      coefficients were 0.45 between OABSS and IPSS total score, 0.55 between OABSS and
      IPSS QOL, and 0.44 between OABSS and PPBC. CONCLUSION: the Indonesian version of
      OABSS showed excellent test-retest reliability in Indonesian OAB patients. A
      satisfactory correlation with IPSS total and QOL scores, PPBC and several
      clinical variables of the 3-day voiding diary was obtained, particularly with
      urgency frequency.

PMID- 22983077
TI  - White coat hypertension may be an initial sign of the metabolic syndrome.
AB  - AIM: to understand the role and significance of WCH in definition of the
      metabolic syndrome. METHODS: the study was performed in the Internal Medicine
      Polyclinic of the Dumlupinar University between August 2005 and March 2007. We
      took consecutive patients at and above the age of 20 years. Their medical
      histories including smoking habit, DM, dyslipidemia, and already used medications
      were learnt, and a routine check up procedure including fasting plasma glucose
      (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C), and an electrocardiography was
      performed. Comparison of proportions was used as the method of statistical
      analysis. RESULTS: the study included 1,068 cases. Prevalences of excess weight
      increased from the third (28.7%) up to the seventh decades (87.0%), gradually
      (p<0.05 nearly in all steps), and then decreased in the eighth (78.5%, p<0.05)
      decade of life. The most significant increase was seen during the passage from
      the third to the fourth decades (28.7% versus 63.6%, p<0.001) with a similar
      fashion to smoking. Hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia,
      impaired glucose tolerance (IGT), and WCH had a similar fashion with excess
      weight by increasing until the seventh decade and decreasing afterwards (p<0.05
      nearly in all steps). Whereas hypertension (HT), type 2 diabetes mellitus (DM),
      and coronary heart disease (CHD) always increased without any decrease by decades
      (p<0.05 nearly in all steps), indicating their irreversible natures. CONCLUSION:
      WCH may be an initial sign of the systemic atherosclerotic process that can be
      detected easily and prevented by a trend towards weight loss.

PMID- 22983078
TI  - Influence of the sorafenib patients assistance program on treatment compliance
      and overall survival  of unresectable hepatocellular carcinoma patients.
AB  - AIM: to evaluate treatment compliance and survival of patients receiving oral
      sorafenib in Indonesia. METHODS: a prospective cohort trial. Unresectable
      Hepatocelullar carcinoma patients receiving Sorafenib in NexPAP program were
      recruited between October 2008 and September 2011. A historical cohort from Cipto
      Mangunkusumo Hospital, between 1998 and 2000 was selected to serve as control
      group. Patients in the control group received symptomatic treatment. Survival
      analysis was done by the Kaplan-Meier survival curve analysis and the log-rank
      test. Median survival difference between the NexPAP and control group was tested
      using the Cox-regression hazard analysis. RESULTS: There were 48 patients in the
      NexPAP group and 40 patients in the control group. Treatment compliance was very
      good; no patient with drew from the study. Sorafenib generally could be tolerated
      by the patients. The most common adverse events are mild or moderate hand and
      foot skin reaction and diarrhea. The median survival was 49 weeks in NexPAP group
      (95% CI 37.9-60.1) vs. 20 weeks in the control group (95% CI 9.0-31.0). Cox
      regression analysis showed that sorafenib significantly prolonged overall
      survival with a hazard ratio (HR) of 0.339 (95% CI: 0.196-0.584). There was no
      survival difference between patients with Child-Pugh class A and class B in both
      NexPAP (median 49 vs. 52 weeks; HR 1.1; 95% CI 0.5-2.3; p=0.855) and control
      groups (27 vs. 20 weeks; HR 1.1; 95% CI 0.5-2.4; p=0.822). CONCLUSION: Sorafenib
      patient assistant program in unresectable hepatocellular carcinoma ensured
      compliance treatment and significantly prolonged overall survival over the
      historical cohort receiving palliative treatment.

PMID- 22983079
TI  - Serum bile acid: an alternative liver function marker in the obstructive jaundice
      patient.
AB  - AIM: to confirm the role of bile acid value as single marker for liver function
      test as compared to the conventional liver function tests on obstructive jaundice
      patients. METHODS: before and after study on severe obstructive jaundice patients
      was performed from December 2007 until January 2009. The liver function markers
      were measured before, 7th day and 14th day after bile duct decompression (BDD).
      Open Cholecystostomy as BDD was used as a model to observe the markers changes.
      Samples were collected by trained medical professionals and Automated clinical
      chemistry analyzer (ACA) TRX 7010 was used to measure the markers value. All
      continuous data were presented as mean (SD) and the variables were compared and
      analyzed by t-test and multiple measurements test using SPSS v.16 with a p-value
      of <0.05 considered to be statistically significant. RESULTS: twenty one patients
      were included. All patients suffered bile acid accumulation and impairment of all
      conventional liver functions tests. After decompression, the average serum bile
      acid decreased significantly (p<0.05). Significant decrease after decompression
      happened to serum total bilirubin (p<0.05) and serum ALP (p<0.05). A trend
      towards improvement in coagulation function was evident by the shortening of PT
      and APTT. The albumin level increased slightly from 2.8 to 2.9 mg/dL while CHE
      activity was fixed at low level. A decrease in average activity of transaminase
      enzyme (AST (p<0.05) and ALT) was also observed. CONCLUSION: the sBA level follow
      the pattern of changes of classic liver function markers. Serum bile acid could
      be considered to be used as alternative marker to evaluate liver function, which
      is simple and applicable.

PMID- 22983080
TI  - DRESS and Ischemic Stroke.
AB  - DRESS (drug rash eosinophilia and systemic symptoms) is a life threatening
      condition characterized by skin rash, fever, leucocytosis with eosinophilia or
      atypical lymphocytosis, lymphadenopathy, and internal organ involvement. This
      case report would like to describe an interesting case of DRESS coincidence with
      ischemic stroke. A 38 year old woman had been admitted with skin rash and fever
      since four days before. Four weeks before admission she received antibiotic and
      multivitamin for one week. The patient looked ill, with body temperature 38.0
      degrees C. Marked physical findings were cervical lymphadenopathy and
      hepatomegaly. Dermatological examination finding was generalized exanthema.
      Laboratory evaluation showed leucocytosis, eosinophilia, and increased level of
      ALT and AST. During hospitalization the patient also suffered from ischemic
      stroke. Treatments administered in this patient were oxygen, adequate intravenous
      fluid, parenteral nutrition, methyl prednisolone, cethirizin bid, ranitidin bid,
      and antibiotic. The antibiotic treatment in this case was performed with graded
      challenge or test dosing.

PMID- 22983081
TI  - Psychogenic unilateral ptosis with ipsilateral muscle spasm of orbicular oculi.
AB  - This report describes the rare case of a 27-year-old female patient with
      conversion disorder who presented unilateral ptosis with ipsilateral muscle spasm
      of orbicular oculi. The co-existing of ptosis and muscle spasm of orbicular oculi
      indicates that, in accord with prior reports, the overactivity of orbicular oculi
      is essential in psychogenic pseudoptosis.  The co-existing of unilateral ptosis
      and ipsilateral muscle spasm of orbicular oculi in the present case leads us to
      the conclusion that the overactivity of orbicular oculi is essential in
      psychogenic pseudoptosis.

PMID- 22983082
TI  - Acute Kidney Injury (AKI) biomarker.
AB  - The kidney has a remarkable capacity to withstand insults for an extended period
      of time. The sensitivities of individual renal cells to injury vary depending on
      their type, position in the nephron, local vascularization, and the nature of
      injury. The resulting kidney injury is a product of the interplay between cell
      dysfunction, cell death, proliferation, inflammation, and recovery.  The Acute
      Kidney Injury Network (AKIN) defined Acute Kidney Injury (AKI) as "functional and
      structural disorder or signs of renal damage including any defect from blood and
      urine test, or tissue imaging that is less than 3 months". RIFLE (Risk, Injury,
      Failure, Loss, End-Stage Kidney Disease) criteria is the most frequently used
      system. Ideal biomarker for AKI should be affordable, quick and measurable,
      precise and accurate, with prognostic ability to define severity of renal
      dysfunction, specific for renal, increase in the early stage dysfunction, with
      high sensitivity and specificity. Efforts to detect AKI in the earlier stage has
      resulted in some promising biomarkers such as KIM-1, NGAL, IL-18, Clusterin, etc.
      Cystatin C is a biomarker for glomerular filtration function, while 2
      microglobulin, 1-microglobulin, NAG, RBP, IL-18, NGAL, Netrin-1, KIM-1,
      Clusterin, Sodium Hydrogen Exchanger Isoform and Fetuin A are biomarkers for
      tubular reabsorption function.

PMID- 22983083
TI  - Infantile herpes zoster after intrauterine exposure to varicella infection.

PMID- 22983084
TI  - Update on the role of intrapleural fibrinolytic therapy  in the management of
      complicated parapneumonic effusions and empyema.
AB  - A parapneumonic effusion is the collection of exudative fluid in the pleural
      space associated with a concurrent pulmonary infection. Parapneumonic effusions
      account for approximately one-third of all effusions, and about 40% of patients
      with pneumonia develop a concomitant effusion. Patients with pneumonia who
      develop an effusion have an increased risk of morbidity and mortality. Some of
      the excess mortality is due to mismanagement of the parapneumonic effusion.
      Bacterial and white cell metabolism can rapidly turn a simple exudative
      parapneumonic effusion into a multiloculated purulent empyema with low pH and
      high lactate dehydrogenase levels. The optimal approach to treating parapneumonic
      effusions and pleural empyemas remains controversial. Accepted management
      consists of systemic antibiotics and drainage of the pleural cavity, which is
      achieved by either medical chest tube drainage or surgery. Several investigators
      have studied the efficacy and safety of intrapleural fibrinolytics in the
      treatment of pleural effusion and empyema. Intrapleural instillation of
      fibrinolytic agents is undertaken to dissolve fibrinous clots and membranes, to
      prevent fluid sequestration, and hence to improve drainage. Recombinant
      deoxyribonuclease has been reported to improve drainage in a single patient who
      did not respond to fibrinolytic therapy.

PMID- 22983085
TI  - New treatment policy of malaria as a part of malaria control program in
      Indonesia.
AB  - Malaria control program is one of the oldest program in the Ministry of Health
      (MoH) Republic of Indonesia. Started with effort to eradicate malaria in 1959
      through Malaria Eradication Command well known as KOPEM (Komando Pembasmian
      Malaria) then it evolves to Malaria Control Program, Roll Back Malaria Program,
      and the current Malaria Elimination Program. In terms of diagnostic and
      treatment, the policy has formulated by strictly follow evidence-based principles
      as well as technical guided from World Health Organization (WHO).  In 2004, based
      on numerous researches conducted in Indonesia the use of chloroquine was stopped
      and artemisinin-based combination therapy (ACT) was then initiated. For severe
      cases the use of intravenous (iv) Artesunate for cases treated in hospitals and
      intramuscular (im) Arthemeter for cases treated in the primary care setting were
      also introduced. ACT, Artesunate iv, and Artemether im, all are provided
      nationwide through the procurement system. For radical treatment, the
      recommendation in Indonesia is to add primaquine (PQ) to ACT for Plasmodium vivax
      and Plasmodium ovale infections to prevent relapses and for Plasmodium Falciparum
      infection to kill the gametocytes. These recommendations put hope to reduce
      malaria mortality to zero and eventually with other interventions will eliminate
      malaria from the country by 2030. The dissemination of this information is
      important for the policy to apply in practice across the country.

PMID- 22983087
TI  - Sulfate-templated self-assembly of new M4L6 tetrahedral metal organic cages.
AB  - Six equivalents of N,N'-bis(4-aminobenzyl)urea, 12 equivalents of 2
      formylpyridine and four equivalents of FeSO(4) or NiSO(4) undergo subcomponent
      self-assembly in aqueous solution to form tetrahedral cages around a single,
      encapsulated sulfate anion.

PMID- 22983086
TI  - The Mediator complex and transcription elongation.
AB  - BACKGROUND: Mediator is an evolutionarily conserved multisubunit RNA polymerase
      II (Pol II) coregulatory complex. Although Mediator was initially found to play a
      critical role in the regulation of the initiation of Pol II transcription, recent
      studies have brought to light an expanded role for Mediator at post-initiation
      stages of transcription. SCOPE OF REVIEW: We provide a brief description of the
      structure of Mediator and its function in the regulation of Pol II transcription
      initiation, and we summarize recent findings implicating Mediator in the
      regulation of various stages of Pol II transcription elongation. MAJOR
      CONCLUSIONS: Emerging evidence is revealing new roles for Mediator in nearly all
      stages of Pol II transcription, including initiation, promoter escape,
      elongation, pre-mRNA processing, and termination. GENERAL SIGNIFICANCE: Mediator
      plays a central role in the regulation of gene expression by impacting nearly all
      stages of mRNA synthesis. This article is part of a Special Issue entitled: RNA
      polymerase II Transcript Elongation.

PMID- 22983089
TI  - Synthetic two-way communication between mammalian cells.
AB  - The design of synthetic biology-inspired control devices enabling entire
      mammalian cells to receive, process and transfer metabolic information and so
      communicate with each other via synthetic multichannel networks may provide new
      insight into the organization of multicellular organisms and future clinical
      interventions. Here we describe communication networks that orchestrate behavior
      in individual mammalian cells in response to cell-to-cell metabolic signals. We
      engineered sender, processor and receiver cells that interact with each other in
      ways that resemble natural intercellular communication networks such as multistep
      information processing cascades, feed-forward-based signaling loops, and two-way
      communication. The engineered two-way communication devices mimicking natural
      control systems in the development of vertebrate extremities and vasculature was
      used to program temporal permeability in vascular endothelial cell layers. These
      synthetic multicellular communication systems may inspire future therapies or
      tissue engineering strategies.

PMID- 22983090
TI  - RNA processing enables predictable programming of gene expression.
AB  - Complex interactions among genetic components often result in variable systemic
      performance in designed multigene systems. Using the bacterial clustered
      regularly interspaced short palindromic repeat (CRISPR) pathway we develop a
      synthetic RNA-processing platform, and show that efficient and specific cleavage
      of precursor mRNA enables reliable and predictable regulation of multigene
      operons. Physical separation of linked genetic elements by CRISPR-mediated
      cleavage is an effective strategy to achieve assembly of promoters, ribosome
      binding sites, cis-regulatory elements, and riboregulators into single- and
      multigene operons with predictable functions in bacteria. We also demonstrate
      that CRISPR-based RNA cleavage is effective for regulation in bacteria, archaea
      and eukaryotes. Programmable RNA processing using CRISPR offers a general
      approach for creating context-free genetic elements and can be readily used in
      the bottom-up construction of increasingly complex biological systems in a plug
      and-play manner.

PMID- 22983092
TI  - Benzobisoxazole fluorophore vicariously senses amines, ureas, anions.
AB  - A benzobisoxazole-based cruciform fluorophore forms fluorescent complexes with
      simple boronic acids. Through the changes of their fluorescence emission colours,
      these complexes can sense and qualitatively distinguish among structurally
      similar organic nitrogen compounds (amines and ureas) and small organic and
      inorganic anions. Preliminary results suggest that the intensity of this hybrid
      sensor's fluorescent response to chloride anions can be quantitatively correlated
      to chloride concentration.

PMID- 22983091
TI  - Direct identification of ligand-receptor interactions on living cells and
      tissues.
AB  - Many cellular responses are triggered by proteins, drugs or pathogens binding to
      cell-surface receptors, but it can be challenging to identify which receptors are
      bound by a given ligand. Here we describe TRICEPS, a chemoproteomic reagent with
      three moieties--one that binds ligands containing an amino group, a second that
      binds glycosylated receptors on living cells and a biotin tag for purifying the
      receptor peptides for identification by quantitative mass spectrometry. We
      validated this ligand-based, receptor-capture (LRC) technology using insulin,
      transferrin, apelin, epidermal growth factor, the therapeutic antibody
      trastuzumab and two DARPins targeting ErbB2. In some cases, we could also
      determine the approximate ligand-binding sites on the receptors. Using TRICEPS to
      label intact mature vaccinia viruses, we identified the cell surface proteins
      AXL, M6PR, DAG1, CSPG4 and CDH13 as binding factors on human cells. This
      technology enables the identification of receptors for many types of ligands
      under near-physiological conditions and without the need for genetic
      manipulations.

PMID- 22983088
TI  - Rapid control of male typical behaviors by brain-derived estrogens.
AB  - Beside their genomic mode of action, estrogens also activate a variety of
      cellular signaling pathways through non-genomic mechanisms. Until recently,
      little was known regarding the functional significance of such actions in males
      and the mechanisms that control local estrogen concentration with a spatial and
      time resolution compatible with these non-genomic actions had rarely been
      examined. Here, we review evidence that estrogens rapidly modulate a variety of
      behaviors in male vertebrates. Then, we present in vitro work supporting the
      existence of a control mechanism of local brain estrogen synthesis by aromatase
      along with in vivo evidence that rapid changes in aromatase activity also occur
      in a region-specific manner in response to changes in the social or environmental
      context. Finally, we suggest that the brain estrogen provision may also play a
      significant role in females. Together these data bolster the hypothesis that
      brain-derived estrogens should be considered as neuromodulators.

PMID- 22983093
TI  - The transformative promise of aging science.

PMID- 22983095
TI  - The effect of labeling photo documents in wrist arthroscopies on intra- and
      interobserver reliability.
AB  - INTRODUCTION: The reproducibility of diagnoses based on photo documents in wrist
      arthroscopies is limited and is expected to improve if the photos are labeled
      with illustrated structures. AIM: The purpose of this study was to determine the
      effect of labeling photo documents on intra- and interobserver agreement and
      reliability of standard photo documentation in wrist arthroscopies. MATERIALS AND
      METHODS: Digital photographs of 50 arthroscopies were re-evaluated by the surgeon
      as well as by two independent hand surgeons. First the photos were presented
      unlabeled in a random order, then the labeled photos in a uniform order. Intra-
      and interobserver reliability was assessed, and expressed by kappa coefficients.
      RESULTS: Overall, labeling the photos resulted in a slight improvement in intra-
      and interobserver reliability (0.573/0.444/0.420 vs. 0.518/0.412/0.212). The time
      needed to conceive the photo documents, however, was shortened when the photos
      were labeled. The cartilage status was assessed considerably more accurately if
      the photos were labeled (0.556/0.560/0.422 vs. 0.459/0.326/0.240; t test: P =
      0.094). Whereas the SL ligament was assessed more accurately according to labeled
      photos (P = 0.100), the agreement rates for the assessment of other ligament
      structures (TFCC, LT and radiopalmar ligaments) were not substantially affected
      by labeling the photos. On re-evaluation of the unlabeled as well as the labeled
      photos, intraobserver reliability was better than interobserver reliability
      (0.518 vs. 0.412/0.212 and 0.573 vs. 0.444/0.420). CONCLUSION: Labeling
      simplifies but does not necessarily improve the reproducibility of photo
      documents in wrist arthroscopies. To display the cartilage status and the
      integrity of the SL ligament, digital photo documents should be labeled with the
      illustrated structure or joint surface.

PMID- 22983094
TI  - Glucose--a sweet way to die: metabolic switching modulates tumor cell death.
AB  - TRAIL, a putative anticancer cytokine, induces extrinsic cell death by activating
      the caspase cascade directly (Type I cells) via the death-inducing signaling
      complex (DISC) or indirectly (Type II cells) by caspase-8 cleavage of Bid and
      activation of the mitochondrial cell death pathway. Cancer cells are
      characterized by their dependence on aerobic glycolysis, which, although
      inefficient in terms of ATP production, facilitates tumor metabolism. Our studies
      show that TRAIL-induced cell death is significantly affected by the metabolic
      status of the cell. Inhibiting glycolysis with 2-deoxyglucose potentiates TRAIL
      induced cell death, whereas glucose deprivation can paradoxically inhibit
      apoptosis. These conflicting responses to glycolysis inhibition are modulated by
      the balance between the Akt and AMPK pathways and their subsequent downstream
      regulation of mTORC1. This results in marked changes in protein translation, in
      which the equilibrium between anti- and pro-apoptotic Bcl-2 family member
      proteins is decided by their individual degradation rates. This regulates the
      mitochondrial cell death pathway and alters its sensitivity not only to TRAIL,
      but to ABT-737, a Bcl-2 inhibitor. Taken together, our studies show that the
      sensitivity of cancer cells to apoptosis can be modulated by targeting their
      unique metabolism in order to enhance sensitivity to apoptotic agents.

PMID- 22983096
TI  - Is bipolar hemiarthroplasty a reliable option for Ficat stage III osteonecrosis
      of the femoral head? 15- to 24-year follow-up study.
AB  - PURPOSE: The long-term results of a bipolar hemiarthroplasty (BHA) for
      osteonecrosis (ON) of the femoral head have not been favorable. The causes have
      been attributed to cup migration and osteolysis or groin pain. The purpose of
      this study was to analyze the long-term outcomes and the survivorships of bipolar
      hemiarthroplasty applied to Ficat stage III ON. MATERIALS AND METHODS: Between
      1985 and 1993, 49 patients (63 hips) underwent cementless BHA for Ficat stage III
      ON. Of these 49 patients, 43 patients (55 hips) of mean age 42.2 years were
      available for follow-up review at a mean duration of 20.3 years post operation.
      Anteroposterior hip serial (including extreme abduction/adduction) radiographs
      were used to evaluate osteolysis, migration, cartilage wear rate, and the ratio
      of outer/inner bearing motion (O/I ratio) at the latest follow-up. RESULTS: The
      mean Harris hip score improved to 80.8 points at the latest follow-up.
      Survivorship at 24 years was 79 and 69 % with revision for any reason and
      development of acetabular osteolysis as the end point. Groin pain was present in
      20 (36.4 %) of the 55 hips, and isolated groin pain was not a reason for
      revision. The patients had revision surgery performed, which showed that the
      cartilage wear rate was significantly high, and that the O/I ratio was
      significantly low (p < 0.05). CONCLUSION: Survivorship determined in this study
      was more favorable than that of previous studies, and exceeded expectation. The
      BHA for Ficat stage III ON is not reliable option anymore, considering low
      survival rate and high osteolysis developmental rate.

PMID- 22983098
TI  - Photochemistry of 1-allyl-4-aryltetrazolones in solution; structural effects on
      photoproduct selectivity.
AB  - The photochemistry of tetrazolones derived from the carbocyclic allylic alcohols
      cyclohex-2-enol and 3-methylcyclohex-2-enol and from the natural terpene alcohol
      nerol was investigated in solution with the aim of assessing the effect of
      solvent and of structural constraints imposed by bulky allylic moieties on
      photoproduct selectivity and stability. Photolysis of tetrazolones derived from
      nerol and cyclohex-2-enol afforded the corresponding pyrimidinones as major
      products through a pathway that appears to be similar to that proposed for other
      1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones derived from acyclic and
      unhindered allylic alcohols previously investigated but photolysis of the
      tetrazolone derived from the bulkier 3-methylcyclohex-2-enol 4c leads to
      formation of a benzimidazolone, indicating that, in this case, cyclization of the
      biradical formed upon extrusion of N(2) involves the phenyl substituent and not
      the allylic moiety. Theoretical calculations (DFT(B3LYP)/3-21G*) were conducted
      to support the interpretation of the experimental results and mechanistic
      proposals. Laser flash photolysis experiments were conducted with the aim of
      clarifying the nature of the intermediate involved in the primary photocleavage
      process.

PMID- 22983097
TI  - Persistent effects of prior chronic exposure to corticosterone on reward-related
      learning and motivation in rodents.
AB  - BACKGROUND: Repeated or prolonged exposure to stress has profound effects on a
      wide spectrum of behavioral and neurobiological processes and has been associated
      with the pathophysiology of depression. The multifaceted nature of this disorder
      includes despair, anhedonia, diminished motivation, and disrupted cognition, and
      it has been proposed that depression is also associated with reduced reward
      motivated learning. We have previously reported that prior chronic corticosterone
      exposure to mice produces a lasting depressive-like state that can be reversed by
      chronic antidepressant treatment. METHODS: In the present study, we tested the
      effects of prior chronic exposure to corticosterone (50 MUg/ml) administered to
      rats or to mice in drinking water for 14 days followed by dose-tapering over 9
      days. RESULTS: The exposure to corticosterone produced lasting deficits in the
      acquisition of reward-related learning tested on a food-motivated instrumental
      task conducted 10-20 days after the last day of full dose corticosterone
      exposure. Rats exposed to corticosterone also displayed reduced responding on a
      progressive ratio schedule of reinforcement when tested on day 21 after exposure.
      Amitriptyline (200 mg/ml in drinking water) exposure for 14 days to mice produced
      the opposite effect, enhancing food-motivated instrumental acquisition and
      performance. Repeated treatment with amitriptyline (5 mg/kg, intraperitoneally;
      bid) subsequent to corticosterone exposure also prevented the corticosterone
      induced deficits in rats. CONCLUSIONS: These results are consistent with aberrant
      reward-related learning and motivational processes in depressive states and
      provide new evidence that stress-induced neuroadaptive alterations in cortico
      limbic-striatal brain circuits involved in learning and motivation may play a
      critical role in aspects of mood disorders.

PMID- 22983100
TI  - [Molecular pathology of gastric cancer].
AB  - Gastric cancer is one of the most common cancers worldwide. In recent decades,
      major advancements in the understanding of the epidemiology, pathology and
      pathogenesis of gastric cancer have been witnessed. Infections with Helicobacter
      pylori or Epstein-Barr virus, dietary and lifestyle factors contribute to the
      risk of developing gastric cancer. With respect to pathogenesis at least three
      distinct types of gastric cancer exist, (1) proximal, (2) distal diffuse and (3)
      distal non-diffuse types. Genetic and epigenetic alterations are related to
      oncogene mutations and tumor suppressor gene inactivation. Canonical oncogenic
      pathways such as the WNT/beta-catenin signaling pathway are de-regulated in
      gastric cancer. Hereditary and familial type gastric cancers are currently linked
      to CDH1 gene mutations and various genetic polymorphisms determining disease
      susceptibility. Molecular subtypes of gastric cancer have been identified which
      separate diffuse from intestinal type gastric cancer and are not entirely
      congruent with the histopathological phenotype according to Lauren but may
      influence chemosensitivity. Putative cancer stem cell markers of gastric cancer
      have been found (e.g. ADAM17, CD133, FZD7, LGR5) and correlate with patient
      prognosis. Thus, molecular phenotyping of gastric cancer is still in its infancy
      and the search for novel diagnostic, prognostic and predictive biomarkers
      continues.

PMID- 22983101
TI  - [Normal bone marrow and common reactive alterations].
AB  - Histological examination of bone marrow biopsies is an important and powerful
      diagnostic tool to assess various hematological and non-hematological disorders.
      Morphological examination of such biopsies requires knowledge of the composition
      of normal bone marrow and its variations, such as age-related changes. Diagnostic
      problems may arise due to poor specimen quality, insufficient sections or
      stainings and insufficient experience with reactive bone marrow changes which
      occasionally resemble neoplastic disorders. Reactive bone marrow processes can
      affect one or more hematopoietic cell lines, lead to disruption of the normal
      architecture and specifically affect the bone marrow stroma. Optimal bone marrow
      diagnosis requires adequately stained slides and, when needed, immunophenotyping
      and molecular examinations. Furthermore, rather than biopsy interpretation of
      other organs, pathologists routinely need clinical history information for
      correct interpretation and diagnosis of bone marrow changes. In this article, the
      normal features of bone marrow as well as the most frequent reactive bone marrow
      alterations are described.

PMID- 22983102
TI  - The effect of a small dose of ketamine  on postoperative analgesia and cytokine
      changes after laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: In this study we assesed the effect of a small dose of
      ketamine on the production of TNFalpha, IL-1beta and IL-6 and the postoperative
      pain in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients
      undergoing laparoscopic cholecystectomy were randomized in two equal groups.
      Patients in the ketamine group after induction in anesthesia received ketamine-
      025 mg/kg(-1). At the same time patients from the control group received sodium
      chloride. Postoperatively, the pain was assessed with VAS at periods of 30 min at
      1, 2, 4, 8, 18, 24 and 48 hours. TNFalpha, IL-1beta and IL-6 were evaluated
      before surgery at 4, 18 and 24h after the operation. RESULTS: Differences of mean
      values of TNFalpha and IL-1beta between the two groups in the postoperative
      period were not significant. Mean values of IL-6 in the investigated group A were
      significantly lower than the mean values of IL-6 in the investigated group B
      after the 4th hour (p=0.00990), after the 18th hour (p=0.00133) and as after the
      24th hour following surgery (p=000860). the difference in pain intensity
      according to the VAS scale was also statistically significantly smaller in group
      A after 30 min, 1,2,8 and 12 hours after surgery. CONCLUSIONS: The addition of a
      small-dose of ketamine in patiens undergoing laparoscopic cholecystectomy
      resulted in attenuation of secretion of TNFalpha, IL-1beta, IL-6 and reduction of
      postoperative pain.

PMID- 22983103
TI  - Comparative analysis of maxillary lateral human incisors in the middle ages and
      today.
AB  - Maxillary lateral incisors are teeth that attract great attention aestheticall
      because of their location in the dental arch. On the other hand, they are
      unstable teeth. Maxillary lateral incisors come in different shapes and sizes.
      Often, as a result of hereditary factors, there is a hypodontio in deciduous and
      permanent dentition. In professional literature, there are no precisely defined
      physiological dimensions for maxillary lateral incisors. As for making a
      comparative analysis, it is necessary to perform measurements of the same, taking
      a particular group of respondents from today and samples from people who lived in
      the Middle Ages on our territory (IX-XII, XIV, XVI and XVIII centuries). This
      research included two different groups of respondents: people from the 21st
      century and samples from people who lived in the Middle Ages from various sites
      on this territory (IX-XII, XIV, XVI and XVIII centuries). Both sexes were
      analysed, between the ages of 14 and 55. As for the analysis of the morphology of
      the teeth, we used methods of observation, photographing and comparing, and as
      for the dimensions, we used a counter. Making a comparative analysis of the
      morphology and size of maxillary lateral incisors to a human of the middle Ages
      and of today, one can come to the conclusion that there has been an increase in
      the width and a slight reduction in the length of the teeth in a human being of
      today. In terms of the sexes, spreading of the teeth was observed and concluded
      in both sexes, with a reduction in the length of teeth in females of today. There
      are no differences among males.

PMID- 22983104
TI  - Compressive strength and setting time determination of glass-ionomer cements
      incorporated with cetylpyridinium chloride  and benzalkonium chloride.
AB  - Because of the relatively frequent occurrence of recurrent caries after a
      restorative treatment, and because of the huge number of cariogenic
      microorganisms present in the oral cavity, which present a potential risk factor
      regarding the development of new carious lesions, attention has increasingly been
      directed towards the therapeutic antimicrobial effects of restorative materials.
      The glass ionomer cements distinguish themselves as the most acceptable
      restorative materials possessing the positive characteristics of fluorine in the
      processes of remineralisation and antimicrobial action. In addition to the
      release of fluoride ions, GICs can potentially be used as templates for the
      release of other active antimicrobial components. The addition of antimicrobial
      compounds in the glass ionomer cements and analysis of their physical
      characteristics are very important especially for use in the posterior region of
      milk teeth. The aim of this study was to analyse the physical characteristics of
      ChemFlex and Fuji IX, conventional glass ionomer cements incorporated with the
      antimicrobial components Cetylpyridinium Chloride and Benzalkonium Chloride,
      through measurements of their setting times, and determination of their
      compressive strengths. Five samples of each glass ionomer with no antimicrobial
      compounds added were prepared--to serve as a control group; and collections of
      five samples of each cement with different concentrations of Cetylpyridinium
      Chloride and Benzalkonium Chloride--1%, 2% and 3%--added to them were also
      prepared--a total of 60 samples. The results of the analysis point out that it is
      possible to incorporate these antimicrobial agents in conventional GICs, and this
      is especially true when the added amount of the antimicrobial agents is 1%.

PMID- 22983105
TI  - In vivo study of pulp reaction to glass ionomer cements and dentin adhesives.
AB  - The aim of this study was to evaluate histopathologically the pulp tissue
      response of the researched materials 7 and 30 days after their application. The
      reaction of pulp tissue has been examined on first upper molars in 24 Wistar
      rats, following the previously set parameters. For that purpose, 48 class V
      cavities were prepared with a high-speed handpiece using a diamond burr under
      copious water-cooling. The cavities were divided into four groups. In the
      cavities from the first group we applied Fuji Lining LC, and in the secound group
      cavities we applied Fuji IX as a base. In the third and fourth group cavities we
      applied Prime and Bond and G Bong as a base. All the cavities were restored with
      liquid light cured composite. Seven days after the application, 3 rats from each
      group were killed and the restored teeth were extracted and immersed in a
      fixative solution, Osteomol. After removing the Osteomol, the specimens were
      processed according to histological procedures. The histological evaluation was
      made using a light microscope connected to a video camera. Thirty days after the
      application of the dental materials we re-did the procedure with the other
      restored teeth. For Fuji Lining LC and Fuji IX most of the specimens exhibited no
      pulpal response or slight inflammatory reaction associated with slight tissue
      disorganization during a seven-day period. A slight to moderate inflammatory
      pulpal response occurred in the specimens restored with G Bond, while Prime and
      Bond exhibited the strongest toxic effect on the pulp tissue. After 30 days the
      pulp tissue in all groups recovered and displayed a normal appearance.

PMID- 22983106
TI  - The effect of various dental filling materials on artificially demineralized
      dentin.
AB  - The aim of this study was to determinate the influence of fluoride, released by
      all of the restorative materials in the process of remineralization. To achieve
      this, we measured the concentration of the incorporated fluoride and calcium in
      dentin. The research was done on 80 extracted third molars, in which we prepared
      first-class cavities. After the process of decalcination, we split the teeth into
      four differ-rent groups (with 20 in each). The teeth from each group were
      separated vertically, in two halves. On the experimental half we applied the
      examined material (Fiji IX, Fuji Lining LC, G Bond and Prime and Bond) and we
      used the other half as a control. Later, the specimens were put into a glass bowl
      together with remineralization solution and were incubated at a temperature of 37
      C. The incorporated fluoride and calcium concentration was determined by a
      significant increase of spectrometer. After applying the specimens in a
      remineralization solution, we perceived that the level of incorporated Ca2+ on
      the teeth restored with Fuji IX and Fuji Lining LC was significantly higher
      compared to the level of incorporated Ca2+ on the teeth, restored with dentin
      materials. Based on the results from this experiment, the conclusion shows that
      fluoride, released from the materials and incorporated into the dentin, speeds up
      the process of remineralization on hard dental tissues.

PMID- 22983107
TI  - Lymphopaenia, anti-Ro/anti-RNP autoantibodies, renal involvement and
      cyclophosphamide use correlate with increased risk of herpes zoster in patients
      with systemic lupus erythematosus.
AB  - Herpes zoster occurs with increased frequency in patients with systemic lupus
      erythematosus (SLE). The aim of this study was to identify and evaluate clinical
      and laboratory risk factors associated with development of herpes zoster in
      patients with SLE. A retrospective case-control study was performed in a
      population of patients with SLE. Patients were identified as cases if their first
      episode of herpes zoster occurred after diagnosis of SLE. Patients with SLE who
      never developed herpes zoster were enrolled as controls. Medical charts and
      laboratory data for both cases and control patients were comprehensively
      reviewed. A total of 65 cases and 105 controls were included. Risk factors
      associated with the development of herpes zoster in patients with SLE were found
      to be lymphopaenia, anti-Ro antibodies, anti-RNP antibodies, neuropsychiatric
      manifestations, renal involvement and cyclophosphamide use. Therefore, the
      presence of certain disease manifestations in patients with SLE represents risk
      factors for the development of herpes zoster.

PMID- 22983108
TI  - Heterogeneous asymmetric Henry-Michael one-pot reaction synergically catalyzed by
      grafted chiral bases and inherent achiral hydroxyls on mesoporous silica surface.
AB  - Highly efficient and enantioselective asymmetric Henry-Michael one-pot reaction
      has been achieved on bifunctional heterogeneous catalysts with inherent achiral
      hydroxyls as acidic sites and immobilized chiral amines as basic sites. Final
      products were afforded in yields of up to 85% and ee of 99%.

PMID- 22983110
TI  - Frequent detection and characterization of hepatitis E virus variants in wild
      rats (Rattus rattus) in Indonesia.
AB  - One hundred sixteen rats (Rattus rattus) captured in Indonesia from 2011 to 2012
      were investigated for the prevalence of hepatitis E virus (HEV)-specific
      antibodies and HEV RNA. Using an ELISA based on HEV genotype 4 with an ad hoc
      cutoff value of 0.500, 18.1 % of the rats tested positive for anti-HEV IgG. By
      nested RT-PCR, 14.7 % of the rats had rat HEV RNA, and none were positive for HEV
      genotype 1-4. A high HEV prevalence among rats was associated with lower sanitary
      conditions in areas with a high population density. Sixteen of the 17 HEV
      isolates obtained from infected rats showed >93.0 % nucleotide sequence identity
      within the 840-nucleotide ORF1-ORF2 sequence and were most closely related to a
      Vietnamese strain (85.9-87.9 % identity), while the remaining isolate differed
      from known rat HEV strains by 18.8-23.3 % and may belong to a novel lineage of
      rat HEV. These results suggest a wide distribution of rat HEV with divergent
      genomes.

PMID- 22983111
TI  - Predominance of tomato leaf curl Gujarat virus as a monopartite begomovirus:
      association with tomato yellow leaf curl Thailand betasatellite.
AB  - Tomato leaf curl is a serious malady in the state of Maharashtra, India, causing
      nearly 100 % yield loss. An extensive survey was done in the affected fields of
      tomato in the year 2008, and members of three species of begomoviruses were
      identified as causing the disease. More than 60 % of the samples from diseased
      plants were infected with tomato leaf curl Gujarat virus (ToLCGuV). Isolates
      collected from these fields differed from the Varanasi isolate of ToLCGuV in not
      having a DNA B component. Instead, they were like typical Old World monopartite
      begomoviruses in that they were associated with only one betasatellite, tomato
      yellow leaf curl Thailand betasatellite (TYLCTHB). ToLCGuV alone is readily
      infectious, expressing systemic symptoms in Nicotiana benthamiana and tomato. Co
      inoculation of ToLCGuV with TYLCTHB, increased symptom severity and reduced the
      incubation time required for symptom expression. ToLCGuV successfully interacted
      with heterologous DNA B component of ToLCNDV [IN:Pun:JID:08], and co-inoculation
      of these two resulted in yellow mottling symptoms that were typical of DNA B.

PMID- 22983112
TI  - Trypsin-dependent hemagglutination of erythrocytes of a variety of mammalian and
      avian species by Alkhumra hemorrhagic fever virus.
AB  - Alkhumra hemorrhagic fever virus (AHFV) is an emerging flavivirus that was
      discovered in 1994-1995 in Saudi Arabia. Clinical manifestations of AHFV
      infection include hemorrhagic fever, hepatitis, and encephalitis, with a reported
      mortality rate as high as 25 %. Biological characteristics of this virus have not
      been well defined. Agglutination of erythrocytes (hemagglutination) is a
      laboratory tool for studying the attachment of viruses to cellular receptors. The
      envelope protein contains sites for attachment to host receptors to initiate the
      process of infection and is thus an essential component of the virion. In the
      present study, we examined the ability of AHFV to agglutinate erythrocytes of 13
      mammalian and avian species (human group O+, camel, cow, sheep, goat, rabbit,
      guinea pig, mouse, rat, chicken, duck, goose and turkey) with and without trypsin
      treatment. Without trypsin treatment, AHFV failed to agglutinate erythrocytes of
      all examined species. Following trypsin treatment, AHFV agglutinated erythrocytes
      of five species, namely, goose, human group O+, rat, guinea pig, and mouse, in
      descending order of sensitivity. This trypsin-dependent hemagglutination test has
      potential for use in serological and functional studies of AHFV.

PMID- 22983113
TI  - Determination of 19 cardiac troponin I and T assay 99th percentile values from a
      common presumably healthy population.
AB  - BACKGROUND: Between-assay comparability of 99th percentiles for cardiac troponin
      concentrations has not been assessed systematically in a single population for a
      large number of assays. METHODS: We determined 99th percentiles for 19 cardiac
      troponin assays in heparin plasma samples from a population of 272 and 252
      presumably healthy males and females, respectively. The assays evaluated included
      1 cardiac troponin T (cTnT) assay from Roche and 18 cTnI assays from Abbott,
      Alere, Beckman, bioMerieux, Instrumentation Laboratory, Ortho-Clinical
      Diagnostics, Singulex, Siemens, and Roche. Five of these assays were categorized
      as high-sensitivity, 9 as sensitive-contemporary, and 5 as point-of-care (POC)
      assays. RESULTS: For high-sensitivity cTnI (hs-cTnI) assays 99th percentiles
      varied from 23 to 58 ng/L. At least 80% of individuals had measurable hs-cTnI,
      whereas only 25% had measurable high-sensitivity cTnT. All high-sensitivity
      cardic troponin assays had 99th percentiles that were 1.2-2.4-fold higher in
      males than females. For the 9 sensitive-contemporary cTnI assays, 99th
      percentiles varied from 12 to 392 ng/L, and only the Beckman assay gave
      measurable concentrations in a substantial portion of the population (35% vs <=6%
      for the others). Seven of these 9 assays had 1.3-5.0-fold higher 99th percentiles
      for males than females. For 5 cTnI POC assays, 99th percentiles varied from <10
      to 40 ng/L. The Instrumentation Laboratory assay gave measurable results in 27.8%
      of study participants vs <=6% for the others. Correlations were generally poor
      among assays. CONCLUSIONS: Among cardiac troponin assays 99th percentile
      concentrations appear to differ. High-sensitivity assays provide measurable
      cardiac troponin results in a substantially greater fraction of presumably
      healthy individuals.

PMID- 22983114
TI  - Active Wnt proteins are secreted on exosomes.
AB  - Wnt signalling has important roles during development and in many diseases. As
      morphogens, hydrophobic Wnt proteins exert their function over a distance to
      induce patterning and cell differentiation decisions. Recent studies have
      identified several factors that are required for the secretion of Wnt proteins;
      however, how Wnts travel in the extracellular space remains a largely unresolved
      question. Here we show that Wnts are secreted on exosomes both during Drosophila
      development and in human cells. We demonstrate that exosomes carry Wnts on their
      surface to induce Wnt signalling activity in target cells. Together with the
      cargo receptor Evi/WIs, Wnts are transported through endosomal compartments onto
      exosomes, a process that requires the R-SNARE Ykt6. Our study demonstrates an
      evolutionarily conserved functional role of extracellular vesicular transport of
      Wnt proteins.

PMID- 22983115
TI  - Auxin regulates aquaporin function to facilitate lateral root emergence.
AB  - Aquaporins are membrane channels that facilitate water movement across cell
      membranes. In plants, aquaporins contribute to water relations. Here, we
      establish a new link between aquaporin-dependent tissue hydraulics and auxin
      regulated root development in Arabidopsis thaliana. We report that most aquaporin
      genes are repressed during lateral root formation and by exogenous auxin
      treatment. Auxin reduces root hydraulic conductivity both at the cell and whole
      organ levels. The highly expressed aquaporin PIP2;1 is progressively excluded
      from the site of the auxin response maximum in lateral root primordia (LRP)
      whilst being maintained at their base and underlying vascular tissues. Modelling
      predicts that the positive and negative perturbations of PIP2;1 expression alter
      water flow into LRP, thereby slowing lateral root emergence (LRE). Consistent
      with this mechanism, pip2;1 mutants and PIP2;1-overexpressing lines exhibit
      delayed LRE. We conclude that auxin promotes LRE by regulating the spatial and
      temporal distribution of aquaporin-dependent root tissue water transport.

PMID- 22983117
TI  - Interaction of naphthalene derivatives with lipids in membranes studied by the 1H
      nuclear Overhauser effect and molecular dynamics simulation.
AB  - The location, orientation, and dynamics of hydrophobic small molecules in lipid
      membranes are studied through combined use of solution-state (1)H-NMR and MD
      simulation. 1-Naphthol and 1-methylnaphthalene were adopted as the small
      molecules with or without hydrophilic groups. The nuclear Overhauser effect (NOE)
      measurement was performed for large unilamellar vesicles (100 nm in diameter)
      composed of dimyristoylphosphatidylcholine (DMPC) and the naphthalene derivative.
      The transient NOE-SE (spin-echo) scheme previously reported (J. Phys. Chem. B,
      2011, 115, 9106-9115) was employed to quantitatively determine the NOE cross
      relaxation rate constant between DMPC and the naphthalene derivative. The
      observed NOE shows that both the naphthalene derivatives distribute over a wide
      domain across the normal of the essentially planar membrane ranging from the
      hydrophobic core to the hydrophilic headgroup. The experimental NOE information
      was further refined in combination with the analysis of time correlation
      functions in MD simulation. It was found that 1-naphthol exhibits a slight
      preference for pointing its OH group toward the hydrophilic domain of the
      membrane and that no definite preference can be concluded for the orientation of
      1-methylnaphthalene. When 1-naphthol and 1-methylnaphthalene are compared, the
      NOE is stronger for 1-naphthol due to the restricted motion of the OH group. The
      slowdown of the 1-naphthol motion is also evidenced by the (1)H spectral line
      width.

PMID- 22983116
TI  - Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to
      regulate insulin production and secretion.
AB  - Endoplasmic reticulum (ER) stress causes pancreatic beta-cell dysfunction and
      contributes to beta-cell loss and the progression of type 2 diabetes. Wolfram
      syndrome 1 (WFS1) has been shown to be an important regulator of the ER stress
      signalling pathway; however, its role in beta-cell function remains unclear. Here
      we provide evidence that WFS1 is essential for glucose- and glucagon-like peptide
      1 (GLP-1)-stimulated cyclic AMP production and regulation of insulin biosynthesis
      and secretion. Stimulation with glucose causes WFS1 translocation from the ER to
      the plasma membrane, where it forms a complex with adenylyl cyclase 8 (AC8), an
      essential cAMP-generating enzyme in the beta-cell that integrates glucose and GLP
      1 signalling. ER stress and mutant WFS1 inhibit complex formation and activation
      of AC8, reducing cAMP synthesis and insulin secretion. These findings reveal that
      an ER-stress-related protein has a distinct role outside the ER regulating both
      insulin biosynthesis and secretion. The reduction of WFS1 protein on the plasma
      membrane during ER stress is a contributing factor for beta-cell dysfunction and
      progression of type 2 diabetes.

PMID- 22983118
TI  - The neurotoxicity of hallucinogenic amphetamines in primary cultures of
      hippocampal neurons.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4
      iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with
      addictive properties. The hippocampus is involved in learning and memory and
      seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the
      neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus
      obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in
      culture were exposed for 24 or 48 h either to MDMA (100-800 MUM) or DOI (10-100
      MUM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based
      (MTT) assays revealed a concentration- and time-dependent neuronal death and
      mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a
      significant increase in caspase-8 and caspase-3 activities. At concentrations
      that produced similar levels of neuronal death, DOI promoted a higher increase in
      the activity of both caspases than MDMA. In the mitochondrial fraction of neurons
      exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of
      apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI
      promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons.
      Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an
      irreversible antagonist) greatly attenuated neuronal death promoted by 48 h
      exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted
      programmed neuronal death involving both the mitochondria machinery and the
      extrinsic cell death key regulators. Death was dependent, at least in part, on
      the stimulation of the 5-HT(2A)-receptors.

PMID- 22983119
TI  - Compound-specific effects of mutations at Val787 in DII-S6 of Nav 1.4 sodium
      channels on the action of sodium channel inhibitor insecticides.
AB  - Sodium channel inhibitor (SCI) insecticides are hypothesized to inhibit voltage
      gated sodium channels by binding selectively to the slow-inactivated state.
      Replacement of valine at position 787 in the S6 segment of homology domain II of
      the rat Na(v)1.4 sodium channel by lysine (V787K) enchances slow inactivation of
      this channel whereas replacement by alanine or cysteine (V787A and V787C)
      inhibits slow inactivation. To test the hypothesis that SCI insecticides bind
      selectively to the slow-inactivated state, we constructed mutated Na(v)1.4/V787A,
      Na(v)1.4/V787C, and Na(v)1.4/V787K cDNAs, expressed wildtype and mutated channels
      with the auxiliary beta1 subunit in Xenopus oocytes, and used the two-electrode
      voltage clamp technique to examine the effects of these mutations on channel
      inhibition by four SCI insecticides (indoxacarb, its bioactivated metabolite
      DCJW, metaflumizone, and RH3421). Mutations at Val787 affected SCI insecticide
      sensitivity in a manner that was independent of mutation-induced changes in slow
      inactivation gating. Sensitivity to inhibition by 10 MUM indoxacarb was
      significantly increased in all three mutated channels, whereas sensitivity to
      inhibition by 10 MUM metaflumizone was significantly reduced in Na(v)1.4/V787A
      channels and completely abolished in Na(v)1.4/V787K channels. The effects of
      Val787 mutations on metaflumizone were correlated with the hydrophobicity of the
      substituted amino acid rather than the extent of slow inactivation. None of the
      mutations at Val787 significantly affected the sensitivity to inhibition by DCJW
      or RH3421. These results demonstrate that the impact of mutations at Val787 on
      sodium channel inhibition by SCI insecticides depend on the specific insecticide
      examined and is independent of mutation-induced changes in slow inactivation
      gating. We propose that Val787 may be a unique determinant of metaflumizone
      binding.

PMID- 22983120
TI  - Course setting and selected biomechanical variables related to injury risk in
      alpine ski racing: an explorative case study.
AB  - BACKGROUND: Course setting has often been discussed as a potential preventative
      measure in the World Cup ski-racing community. However, there is limited
      understanding of how it is related to injury risk. OBJECTIVE: This study was
      undertaken to investigate the effect of increased horizontal gate distance on
      energy-related and injury mechanism-related variables. METHODS: During a video
      based three-dimensional (3D)-kinematic field measurement, a top world-class racer
      performed giant slalom runs at two course settings with different horizontal gate
      distances. A full-body segment model was reconstructed in 3D and selected
      biomechanical parameters were calculated. RESULTS: For the analysed turn, no
      significant differences were found in turn speed for increased horizontal gate
      distance. However, a large effect size was observed for speed reduction towards
      the end of the turn. Turn forces were by tendency higher at the beginning and
      significantly higher towards the end of the turn. Additionally, significant
      differences were found in higher inward leaning, and large effect sizes were
      observed for a decreased fore/aft position after gate passage. CONCLUSIONS: On
      the basis of the data of this study, no final conclusion can be made about
      whether, for a section of consecutive turns, increasing horizontal gate distance
      is an effective tool for speed reduction. However, this study pointed out two
      major drawbacks of this course setting modification: (1) it may increase fatigue
      as a consequence of loading forces acting over a longer duration; (2) it may
      increase the risk of out-of-balance situations by forcing the athlete to exhaust
      his backward and inward leaning spectrum.

PMID- 22983121
TI  - Greater trochanteric pain syndrome: defining the clinical syndrome.
AB  - BACKGROUND: Effective treatment of hip pain improves population health and
      quality of life. Accurate differential diagnosis is fundamental to effective
      treatment. The diagnostic criteria for one common hip problem, greater
      trochanteric pain syndrome (GTPS) have not been well defined. PURPOSE: To define
      the clinical presentation of GTPS. METHODS: Forty-one people with GTPS, 20 with
      hip osteoarthritis (OA), and 23 age-matched and sex-matched asymptomatic
      participants (ASC) were recruited. Inclusion and exclusion criteria ensured
      mutually exclusive groups. ASSESSMENT: the Harris hip score (HHS), a battery of
      clinical tests, and single leg stance (SLS). Participants identified the site of
      reproduced pain. ANALYSIS: Fisher's exact test, analysis of variance (ANOVA)
      informed recursive partitioning to develop two classification trees. RESULTS:
      Maximum walking distance and the ability to manipulate shoes and socks were the
      only HHS domains to differentiate GTPS from OA (ANOVA: p=0.010 and <0.001); OR
      (95% CI) of 3.47 (1.09 to 10.93) and 0.06 (0.00 to 0.26), respectively. The
      lateral hip pain (LHP) classification tree: (dichotomous LHP associated with a
      flexion abduction external rotation (FABER) test) had a mean (SE) sensitivity and
      specificity of 0.81 (0.019) and 0.82 (0.044), respectively. A non-specific hip
      pain classification tree had a mean (SE) sensitivity and specificity of 0.78
      (0.058) and 0.28 (0.080). CONCLUSIONS: Patients with LHP in the absence of
      difficulty with manipulating shoes and socks, together with pain on palpation of
      the greater trochanter and LHP with a FABER test are likely to have GTPS.

PMID- 22983123
TI  - Estimated glomerular filtration rate: why we need it.

PMID- 22983122
TI  - Biomechanical overload syndrome: defining a new diagnosis.

PMID- 22983124
TI  - Revised h index for biomedical research.
AB  - Proposed by Hirsch as a quantitative measure of the total output of a researcher,
      the h index does not work well in the field of life sciences, where an author's
      position on a paper typically depends on the author's contribution. We revise the
      h index by weighing first and last authorship papers four times heavier than
      middle authorship papers. The revised index (r) signifies a shift in how we
      evaluate the research output in biology and medicine: it places more value on
      conducting and directing original, independent investigations as compared with
      contributing to projects conducted and directed by others.

PMID- 22983127
TI  - Origin of DNA replication at the human lamin B2 locus: OBR or ABR?

PMID- 22983128
TI  - The role of rest.

PMID- 22983126
TI  - Putting the brakes on p53-driven apoptosis.
AB  - Following genotoxic stress, cells activate a complex, kinase-based signaling
      network to arrest the cell cycle and initiate DNA repair or apoptosis. The tumor
      suppressor p53 lies at the heart of this DNA damage response. p53 mediates the
      transactivation of both cell cycle-regulating and pro-apoptotic clusters of
      target genes. However, it remains incompletely understood which signaling
      molecules dictate the choice between these two opposing p53-dependent cellular
      outcomes. Over recent years, numerous regulatory mechanisms impacting on the
      cellular outcome of p53 signaling have been described. However, no single
      dominant mechanism has thus far been identified to regulate the cellular choice
      between p53-driven apoptosis or senescence. The transcriptional regulator AATF
      has recently emerged as a novel factor impacting on the cellular outcome of the
      p53 response. Upon genotoxic stress, cytoplasmic pools of MRLC-bound AATF are
      phosphorylated through the p38MAPK/MK2 checkpoint kinase complex. This AATF
      phosphorylation results in the disruption of cytoplasmic MRLC3:AATF complexes
      followed by rapid nuclear localization of AATF. Once in the nucleus, AATF binds
      to the PUMA, BAX and BAK promoters to repress the DNA damage-induced expression
      of these pro-apoptotic p53 target genes. Depletion of AATF in tumor cells results
      in a dramatically enhanced response to DNA-damaging chemotherapeutics, both in
      vitro and in vivo. Furthermore, focal copy number gains at the AATF locus in
      neuroblastoma correlate with adverse prognosis and reduced overall survival in
      this typically p53-proficient malignancy. These data identify the p38/MK2/AATF
      signaling pathway as a critical repressor of p53-driven apoptosis in tumor cells
      and implicate this signaling cascade as a novel target for chemotherapy
      sensitizing therapeutic efforts.

PMID- 22983125
TI  - Sirt1: def-eating senescence?
AB  - Sirt1, the closest mammalian homolog of the Sir2 yeast longevity protein, has
      been extensively investigated in the last few years as an avenue to understand
      the connection linking nutrients and energy metabolism with aging and related
      diseases. From this research effort the picture has emerged of an enzyme at the
      hub of a complex array of molecular interactions whereby nutrient-triggered
      signals are translated into several levels of adaptive cell responses, the
      failure of which underlies diseases as diverse as diabetes, neurodegeneration and
      cancer. Sirt1 thus connects moderate calorie intake to "healthspan," and a
      decline of Sirt-centered protective circuits over time may explain the
      "catastrophic" nature of aging.

PMID- 22983129
TI  - A yoga intervention for music performance anxiety in conservatory students.
AB  - Music performance anxiety can adversely affect musicians. There is a need for
      additional treatment strategies, especially those that might be more acceptable
      to musicians than existing therapies. This pilot study examined the effectiveness
      of a 9-week yoga practice on reducing music performance anxiety in undergraduate
      and graduate music conservatory students, including both vocalists and
      instrumentalists. The intervention consisted of fourteen 60-minute yoga classes
      approximately twice a week and a brief daily home practice. Of the 24 students
      enrolled in the study, 17 attended the post-intervention assessment. Participants
      who completed the measures at both pre- and post-intervention assessments showed
      large decreases in music performance anxiety as well as in trait anxiety.
      Improvements were sustained at 7- to 14-month follow-up. Participants generally
      provided positive comments about the program and its benefits. This study
      suggests that yoga is a promising intervention for music performance anxiety in
      conservatory students and therefore warrants further research.

PMID- 22983130
TI  - "You cannot perform music without taking care of your body": a qualitative study
      on musicians' representation of body and health.
AB  - OBJECTIVE: To identify professional musicians' representation of health and
      illness and to identify its perceived impact on musical performance. METHODS: A
      total of 11 professional musicians participated in this phenomenological study.
      Five of the musicians were healthy, and the others suffered debilitating physical
      health problems caused by playing their instruments. Semi-structured interviews
      were conducted, transcribed verbatim and analysed. Thematic analysis, including a
      six-step coding process, was performed (ATLAS-ti 6). RESULTS: Three major themes
      emerged from the data: music as art, the health of musicians, and learning
      through experience. The first theme, music as art, was discussed by both groups;
      they talked about such things as passion, joy, sense of identity, sensitivity,
      and a musician's hard life. Discussions of the second theme, the health of
      musicians, revealed a complex link between health and performance, including the
      dramatic impact of potential or actual health problems on musical careers. Not
      surprisingly, musicians with health problems were more concerned with
      dysfunctional body parts (mostly the hand), whereas healthy musicians focused on
      maintaining the health of the entire person. The third theme, learning through
      experience, focused on the dynamic nature of health and included the life-long
      learning approach, not only in terms of using the body in musical performance but
      also in daily life. CONCLUSIONS: The centre of a musician's life is making music
      in which the body plays an important part. Participants in this study evidenced a
      complex link between health and musical performance, and maintaining health was
      perceived by these musicians as a dynamic balance. Our results suggest that
      learning through experience might help musicians adapt to changes related to
      their bodies.

PMID- 22983131
TI  - Dance floors as injury risk: analysis and evaluation of acute injuries caused by
      dance floors in professional dance with regard to preventative aspects.
AB  - A dance floor is often the only support of movements in dance. A dance floor
      surface that shows deficiencies, can result in acute injuries and chronic
      problems. Although the significance of an adequate dance floor is well known,
      there is still a lack of differentiated analyses of dance floor-related acute
      injuries. OBJECTIVE: This study presents data on acute injuries exclusively
      caused by the dance floor. METHODS: The data were obtained from standardized work
      accident reports from consultants (F 1000), documentary accident records from all
      Berlin theatres, a state ballet school (n=2,281), and case records from the
      Berlin State Accident Insurance (UKB) covering a period of 17 years. All analyses
      and descriptive statistics were conducted with Excel 2007 and SPSS 18. RESULTS:
      Dance floor surfaces were the causative factor in 12.8% of all accidents (n=291,
      female 183, male 108). Almost two thirds (62.6%) of all accidents in professional
      dancers happened on stage, and almost half (49.5%) occurred during performances.
      As for causative factors, 53.1% of the professional dancers (P) and 42.5% of the
      dance students (S) claimed that the floor had been "too slippery," with "getting
      stuck" or (tripping) as the second most common problem (P 18.4%, S 11.3%). Of the
      injured dancers, 41.8% were older than 30 years and can therefore be categorized
      as experienced. CONCLUSION: Dance floors play a significant role in the
      occurrence of acute injuries, even in experienced dancers. Performances on stage
      seem to be a particular risk. However, injury prevention measures should include
      all work locations (P) as well as non-dance-specific locations (S).

PMID- 22983132
TI  - Electromyographic comparison of grand battement devant at the barre, in the
      center, and traveling.
AB  - This study examined utilization of the trunk and lower extremity muscles during
      grand battement devant in three conditions: at the barre (supported stationary
      condition in 1st position), in the center (unsupported stationary condition in
      1st position), and traveling through space. Forty dancers (age 30.0 +/- 13.0 yrs,
      height 1.63 +/- 0.06 m, weight 59.0 +/- 7.4 kg, and 13.9 +/- 13.3 yrs of training
      in ballet and/or modern dance) volunteered and were placed in three skill level
      groups: beginner (n = 12), intermediate (n = 14), and advanced (n = 14). Dancers
      executed five grand battement devant in each of the three conditions in
      randomized order. We examined muscle activation bilaterally in eight muscles
      (abdominals, abductor hallucis, erector spinae, gastrocnemius, gluteus maximus,
      hamstrings, quadriceps, and tibialis anterior) using surface electromyography, a
      three-dimensional video biomechanical tracking system to identify events, and
      force plates. All data were analyzed in four events: stance, initiation, peak,
      and end. Analysis was done using a linear mixed effects regression model with
      condition, event, muscle, level, and side as the fixed effects, and subject as
      the random effect. There were significant effects for muscle x event x condition
      (p<0.01) and for level x side x muscle (p<0.01). Muscle use varied according to
      the combination of event and condition that was executed, and these differences
      were also influenced by the level of training of the dancer and the side of the
      body used. It is recommended that dance educators consider the importance of
      allocating sufficient time to each of the three conditions (barre, center, and
      traveling) to ensure development of a variety of motor strategies and muscle
      activation levels for dance practice.

PMID- 22983133
TI  - Role of female reproductive hormones in musicians' dystonia.
AB  - Musicians' dystonia is an occupational focal dystonia affecting men more often
      than women. METHODS: We identified all patients presenting with musicians'
      dystonia and prospectively collected data on reproductive and menstrual history
      from the women with musician's dystonia and female musicians without dystonia.
      RESULTS: 149 men and 23 women (13.37%) with musician's dystonia where identified.
      We did not identify any effect of contraceptive hormones, pregnancy, or menstrual
      phases on dystonia symptoms, but as compared with women without dystonia, those
      with musician's dystonia reported oligomenorrhea and menometrorrhagia
      significantly less frequently. CONCLUSIONS: Our data reinforce the relation
      between sex hormones variations and musicians' dystonia. This link should be
      further explored to identify mechanisms and assess whether certain hormonal
      interventions might protect from the manifestation of dystonia.

PMID- 22983134
TI  - Core stability: implications for dance injuries.
AB  - Dancers experience a high incidence of injury due to the extreme physical demands
      of dancing. The majority of dance injuries are chronic in nature and occur in the
      lower extremities and low back. Researchers have indicated decreased core
      stability (CS) as a risk factor for these injuries. Although decreased CS is
      suggested to negatively affect lower extremity joint motion and lumbar control
      during activity, this relationship has not been extensively discussed in previous
      dance literature. Understanding the relationship between CS and injury risk is
      important to help reduce dance injury incidence and improve performance. The
      purposes of this review were to discuss: 1. the core and components of CS, 2. the
      relationship between CS and injury, 3. CS assessment techniques, and 4. future
      dance CS research areas. CS is the integration of passive (non-contractile),
      active (contractile), and neural structures to minimize the effects of external
      forces and maintain stability. CS is maintained by a combination of muscle power,
      strength, endurance, and sensory-motor control of the lumbopelvic-hip complex. CS
      assessments include measuring muscle strength and power using maximal voluntary
      isometric and isokinetic contractions and measuring endurance using the Biering
      Sorensen, plank, and lateral plank tests. Measuring sensory-motor control
      requires specialized equipment (e.g., balance platforms). Overall, limited
      research has comprehensively examined all components of CS together and their
      relationships to injury. Rather, previous researchers have separately examined
      core power, strength, endurance, or sensory-motor control. Future researchers
      should explore the multifactorial role of CS in reducing injury risk and
      enhancing performance in dancers.

PMID- 22983135
TI  - Voice rest and phonotrauma in singers.
AB  - Voice rest as first-line empiric treatment for singers has been widely accepted
      as appropriate therapy where obvious laryngeal pathology may not be readily
      apparent. Few guidelines regarding voice rest regimens for singers have been
      published in the literature, and no published recommendations consider
      phonotrauma as the key to predicting the short- and long-term benefit. As a short
      term solution to short-term, noncompounded phonotrauma, voice rest has a definite
      role. As an effective solution to compounded phonotraumatic hoarseness, voice
      rest may be analogous to crash diets in the morbidly obese. Any realized benefits
      are short-lived, and the underlying problem is rarely addressed. This article
      aims to clarify a reasonable role for voice rest in singers as utilized in a busy
      professional voice clinic. The concepts of noncompounded and compounded
      phonotrauma will be introduced and serve as a guide to predicting the success or
      failure of voice rest regimens by basing endpoints on reasonable expectations.

PMID- 22983136
TI  - Opinion of patients with ankylosing spondylitis on risk factors impairing their
      quality of life.
AB  - We studied 54 patients with ankylosing spondylitis with questionnaire in order to
      determine their view on threat to quality of their life related to the disease.
      We have show that pain and significant disability are the main threats associated
      with the disease in view of the patients. Social aspects (losing of job or
      decreasing of income) are also important for the patients, while management of
      the disease is not considered as arduous. The results of patients' opinion may be
      helpful in designing of educational programs for them. 

PMID- 22983137
TI  - The impact of chemical synovectomy with sodium morrhuate on human chondrocytes
      and cartilage in vitro.
AB  - The vessel sclerosing property of sodium morrhuate is useful in treatment of
      recurrent joint effusions particularly in cases of knee joint effusions. It also
      can be employed as an addition to surgical synovectomy. Little is known about the
      effects of this drug on cartilage. This study was designed to investigate the
      cytotoxic impact of sodium morrhuate on human chondrocytes and cartilage tissue
      in vitro. Primary chondrocytes from 13 patients were isolated and cultivated in
      three-dimensional alginate cultures. Furthermore, femoral cartilage explants of
      10 patients were cultivated in vitro. Both chondrocytes and cartilage explants
      were exposed to mixture of sodium morrhuate and mepivacaine in different
      concentrations simulating chemical synovectomy. After 48 h, cell proliferation,
      viability, and cytotoxicity were measured. The cartilage specimens were analyzed
      for apoptosis by immunohistochemistry. Up to a dilution of 1:600, cells were
      found to be 100 % viable with a proliferation rate of 74 % compared to controls.
      From 1:400 onwards, a significant increase in LDH release was measured which
      reached at dilution of 1:200 74 % of high control, whereas histological
      examination showed no proof of apoptosis or necrosis in cartilage tissue. The
      results of this in vitro study demonstrate that the cytotoxic effects of sodium
      morrhuate on human chondrocytes, which lack their original extracellular matrix,
      manifest between dilutions of 1:500 and 1:400 and increase with higher
      concentrations of the drug. This effect was not found for cartilage explants,
      though.

PMID- 22983138
TI  - Orange-brown chromonychia, a novel finding in Kawasaki disease.
AB  - Kawasaki disease (KD) is one of the commonest vasculitis of childhood, where
      diagnosis is clinical based on a plethora of signs and symptoms. One of the
      typical findings is the changes in the extremities including the nail changes.
      Orange-brown chromonychia is a colour change in the nails which has been observed
      in some cases of KD. Here, we report a series of 40 patients of KD, where a
      typical transverse orange-brown discolouration of nails or chromonychia was noted
      in 29 patients. Though chromonychia is noted in many other rheumatic and
      nonrheumatic diseases, the typical transverse orange-brown chromonychia observed
      in KD patients can be included as an additional clinical feature in diagnosis of
      KD.

PMID- 22983140
TI  - A regio- and diastereoselective palladium-catalyzed cyclopropanation of
      norbornene derivatives with molecular oxygen as the sole oxidant.
AB  - A mild and efficient Pd-catalyzed cyclopropanation of norbornene derivatives with
      tertiary propargylic alcohols using molecular oxygen as the sole oxidant is
      described. This process allows quick and atom-economical assembly of various
      1,2,3-trisubstituted cyclopropanes bearing alpha,beta-unsaturated ketone moieties
      in high yields as a single regio- and diastereoisomer.

PMID- 22983139
TI  - Influence of L1-CAM expression of breast cancer cells on adhesion to endothelial
      cells.
AB  - PURPOSE: Expression of the adhesion molecule L1-CAM (L1) has been shown to
      correlate with early recurrence in breast cancer. Here, we investigated whether
      L1-CAM expression of breast cancer cells might influence adherence to human
      pulmonary microvascular endothelial cells (HPMEC) and thus promote metastasis.
      METHODS: MDA-MB231-Fra2 breast cancer cells that express high levels of L1-CAM
      (L1(high) cells) were stably transfected to generate clones with strong L1-CAM
      downregulation. Adhesion to activated HPMEC was studied in dynamic cell flow and
      static assays. Potential binding partners on endothelial cells were identified by
      blocking experiments and adhesion assays after coating of the flow channels with
      recombinant proteins. RESULTS: Adhesion of L1(high) cells to activated HPMEC was
      significantly higher compared to L1l(ow) clones under flow conditions. Blocking
      experiments and adhesion assays with recombinant proteins identified activated
      leucocyte cell adhesion molecule (ALCAM) or L1 itself, but not ICAM-1, as
      potential binding partners on endothelial cells. E-selectin blocking antibodies
      strongly diminished the adherence of breast cancer cells irrespective of their L1
      CAM expression. CONCLUSIONS: Our experiments indicate that L1-CAM expression on
      breast cancer cells can promote adherence to activated endothelial cells by
      binding to endothelial L1-CAM or ALCAM. This mechanism might lead to increased
      metastasis and a poor prognosis in L1-CAM-positive carcinomas in vivo. Therefore,
      L1-CAM might be a suitable therapeutic target in breast cancers with a high L1
      CAM expression.

PMID- 22983141
TI  - Urban Early Adolescent Narratives on Sexuality: Accidental and Intentional
      Influences of Family, Peers, and the Media.
AB  - In this paper, we examine the ways that early adolescents talked, interacted, and
      made references to events in their individual and collective lives during
      photography-based focus groups about sexuality and relationships. Twenty-three
      participants (10 boys and 13 girls) were recruited from three urban schools
      participating in a comprehensive sex education impact evaluation in the
      Northeast. We analyzed conversational narratives that were elicited in a group
      process while sharing photos of important people, contexts, and situations,
      showcasing participants' exploration of sexuality and relationships. Our analysis
      revealed four main themes: (a) direct and indirect family communication about
      sexuality, (b) accidental and intentional Internet usage, (c) shared and
      contested peer knowledge, and (d) school as a direct and indirect learning
      context. Implications and future directions for practice, research, and policy
      are explored.

PMID- 22983142
TI  - Iron uptake and homeostasis related genes in potato cultivated in vitro under
      iron deficiency and overload.
AB  - Potato is one of the most important staple food in the world because it is a good
      source of vitamin C, vitamin B6 but also an interesting source of minerals
      including mainly potassium, but also magnesium, phosphorus, manganese, zinc and
      iron to a lesser extent. The lack of iron constitutes the main form of
      micronutrient deficiency in the world, namely iron deficiency anemia, which
      strongly affects pregnant women and children from developing countries. Iron
      biofortification of major staple food such as potato is thus a crucial issue for
      populations from these countries. To better understand mechanisms leading to iron
      accumulation in potato, we followed in an in vitro culture experiment, by qPCR,
      in the cultivar Desiree, the influence of media iron content on the expression of
      genes related to iron uptake, transport and homeostasis. As expected, plantlets
      grown in a low iron medium (1 mg L(-1) FeNaEDTA) displayed a decreased iron
      content, a strong induction of iron deficiency-related genes and a decreased
      expression of ferritins. Inversely, plantlets grown in a high iron medium (120 mg
      L(-1) FeNaEDTA) strongly accumulated iron in roots; however, no significant
      change in the expression of our set of genes was observed compared to control (40
      mg L(-1) FeNaEDTA).

PMID- 22983143
TI  - Comparison of the formation of nicotinic acid conjugates in leaves of different
      plant species.
AB  - There are three metabolic fates of nicotinic acid in plants: (1) nicotinic acid
      mononucleotide formation for NAD synthesis by the so-called salvage pathway of
      pyridine nucleotide biosynthesis; (2) nicotinic acid N-glucoside formation; and
      (3) trigonelline (N-methylnicotinic acid) formation. In the present study, the
      metabolism of [carbonyl-(14)C]nicotinamide was investigated in leaves of 23 wild
      plant species. All species readily converted nicotinamide to nicotinic acid, and
      only a fraction of nicotinic acid was utilised for NAD and NADP synthesis. The
      remaining nicotinic acid is converted to the nicotinic acid conjugates. Only one
      plant species, Cycas revoluta, produced both nicotinic acid N-glucoside and
      trigonelline; the other 22 species produced one or other of the conjugates. The
      nicotinic acid N-glucoside-forming plants are Cyathea lepifera, Arenga trewmula
      var. englri, Barringtonia racemosa, Ilex paraguariensis, Angelica japonica,
      Scaevola taccada and Farfugium japonicum. In contrast, trigonelline is formed in
      C. lepifera, Ginkgo biloba, Pinus luchuensis, Casuarina equisetifolia, Alocasia
      odora, Pandanus odoratissimus, Hylocereus undatus, Kalanchoe pinnata, Kalanchoe
      tubiflora, Populus alba, Garcinia subelliptica, Oxalis corymbosa, Leucaena
      leucocephala, Vigna marina, Hibiscus tiliaceus and Melicope triphylla. The
      diversity of nicotinic acid conjugate formation in plants is discussed using
      these results and our previous investigation involving a few model plants,
      various crops and ferns. Nicotinic acid N-glucoside formation was restricted
      mostly to ferns and selected orders of angiosperms, whereas other plants produce
      trigonelline. In most cases the formation of both nicotinic acid conjugates is
      incompatible, but some exceptions have been found.

PMID- 22983146
TI  - Predicting grip strength and key pinch using anthropometric data, DASH
      questionnaire and wrist range of motion.
AB  - PURPOSE: The objective of this study was to examine the influence of
      anthropometric data, occupational manual strain, DASH (disability of arm,
      shoulder and hand) score and range of motion (ROM) on grip strength and key
      pinch. An additional goal was to develop models that enable the prediction of
      hand strength using the aforementioned parameters. METHODS: Normative data
      generated from a healthy working population (n = 750) served as basis for the
      statistical analysis. Prediction models for hand strength were developed using
      multivariate regression analysis. RESULTS: Gender, body weight and height, BMI
      and extension ROM correlate positively, age and DASH score, however, correlate
      negatively with grip strength and key pinch. Occupational manual strain has no
      influence on hand strength. The predictive power of the developed models was 68.4
      % for grip strength and 57.1 % for key pinch. CONCLUSIONS: The developed models
      enable the prediction of hand strength using easily obtainable data points. The
      models will have application in clinical practice, physiological studies, medical
      evidence and rehab decisions.

PMID- 22983144
TI  - Enhancement of social novelty discrimination by positive allosteric modulators at
      metabotropic glutamate 5 receptors: adolescent administration prevents adult
      onset deficits induced by neonatal treatment with phencyclidine.
AB  - Metabotropic glutamate-5 receptors (mGluR5), which physically and functionally
      interact with N-methyl-D-Aspartate (NMDA) receptors, likewise control cognitive
      processes and have been proposed as targets for novel classes of antipsychotic
      agent. Since social cognition is impaired in schizophrenia and disrupted by NMDA
      receptor antagonists like dizocilpine, we evaluated its potential modulation by
      mGluR5. Acute administration (0.63-40 mg/kg) of the mGluR5 positive allosteric
      modulators (PAMs), 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and
      ADX47273, reversed a delay-induced impairment in social novelty discrimination
      (SND) in adult rats. The action of CDPPB was blocked by the mGluR5 antagonist, 2
      methyl-6-(phenylethynyl)-pyridine (2.5-10 mg/kg), and was also expressed upon
      microinjection into frontal cortex (0.63-10 MUg/side), but not striatum.
      Supporting an interrelationship between mGluR5 and NMDA receptors, enhancement of
      SND by CDPPB was blocked by dizocilpine (0.08 mg/kg) while, reciprocally,
      dizocilpine-induced impairment in SND was attenuated by CDPPB (10 mg/kg). The SND
      deficit elicited by post-natal administration of phencyclidine (10 mg/kg, days 7
      11) was reversed by CDPPB or ADX47273 in adults at week 8. This phencyclidine
      induced impairment in cognition emerged in adult rats from week 7 on, and
      chronic, pre-symptomatic treatment of adolescent rats with CDPPB over weeks 5-6
      (10 mg/kg per day) prevented the appearance of SND deficits in adults until at
      least week 13. In conclusion, as evaluated by a SND procedure, mGluR5 PAMs
      promote social cognition via actions expressed in interaction with NMDA receptors
      and exerted in frontal cortex. MGluR5 PAMs not only reverse but also (when given
      during adolescence) prevent the emergence of cognitive impairment associated with
      a developmental model of schizophrenia.

PMID- 22983145
TI  - Long-term cognitive impairments induced by chronic cannabinoid exposure during
      adolescence in rats: a strain comparison.
AB  - RATIONALE: During cerebral development, adolescence is a critical phase in which
      the endocannabinoid system plays an important role in regulating various
      neurotransmitters. Moreover, evidence from both human and animal studies suggests
      that chronic cannabinoid exposure during this vulnerable period can induce
      persistent brain and behavioural alterations. OBJECTIVES: The aim of this study
      was to compare the long-term cognitive consequences of chronic adolescence
      cannabinoid exposure between Lister Hooded rats and Wistar rats. METHODS: Rats of
      both strains were injected daily throughout their adolescent or adult periods
      with vehicle or with incremental doses of the synthetic cannabinoid CB1 receptor
      agonist CP55,940 (CP). Short-term and spatial working memories were assessed
      using the object recognition and object location, tasks respectively. For both
      tasks, the effect of a 30- or 120-min delay between the learning and the testing
      phase was investigated. RESULTS: In the object recognition task, adolescent CP
      exposure impaired short-term memory after both delays in both strains. In
      contrast, in the object location task, adolescent CP exposure impaired spatial
      working memory in the Wistar rats after a 30-min delay, whereas the Lister Hooded
      rats exhibited a similar effect only after a 120-min delay. In these tests, no
      long-term deleterious effects were found following adult CP exposure in either
      strain. CONCLUSIONS: Our results confirm that adolescence is a critical period
      for the deleterious effects of cannabinoids on cognition and that these
      deleterious effects on spatial working memory are more strain-dependent than the
      effects observed on short-term memory.

PMID- 22983147
TI  - Letter to the editor: "Role of the human erythrocyte in generation and storage of
      asymmetric dimethylarginine".

PMID- 22983148
TI  - Enhancement of gene silencing effect and membrane permeability by Peptide
      conjugated 27-nucleotide small interfering RNA.
AB  - Two different sizes of siRNAs, of which one type was 21-nucleotide (nt) siRNA
      containing 2-nt dangling ends and the other type was 27-nt siRNA with blunt ends,
      were conjugated with a nuclear export signal peptide of HIV-1 Rev at the 5'-sense
      end. Processing by Dicer enzyme, cell membrane permeability, and RNAi efficiency
      of the peptide-conjugated siRNAs were examined. Dicer cleaved the peptide
      conjugated 27-nt siRNA leading to the release of 21-nt siRNA, whereas the peptide
      conjugated 21-nt siRNA was not cleaved. High membrane permeability and
      cytoplasmic localization was found in the conjugates. Moreover, the peptide
      conjugated 27-nt siRNA showed increased potency of RNAi in comparison with the
      nonmodified 21-nt and 27-nt siRNAs, whereas the peptide-conjugated 21-nt siRNA
      showed decreased RNAi efficacy. This potent RNAi efficacy is probably owing to
      acceleration of RISC through recognition by Dicer, as well as to the improvement
      of cell membrane permeability and intracellular accumulation.

PMID- 22983149
TI  - A 3-D metal-organic framework constructed with manganese(IotaIota), 4,4'
      oxybis(benzoic acid) and 2,2'-biphenyl: synthesis, crystal structure and
      photoelectric property characterization.
AB  - Assembly of 4,4'-oxybis(benzoic acid) (H(2)L) with manganese chloride in the
      presence of 2,2'-biphenyl (2,2'-bpy) affords a new coordination polymer
      [Mn(3)L(3)(2,2'-bpy)(2)](n) (1), in which the [MnL(2)]n layers are extended by L
      bridges resulting in a three-dimensional (3-D) coordination framework. The
      network structure of 1 has unusual (2,6)-connectivity and represents a new type
      of (8(12) . 12(3))(8)(3) topology. These identical and complementary networks are
      entangled to generate a self-penetrating supramolecular lattice. Moreover, the
      fluorescence spectrum of 1 exhibits fluorescent emission in the solution of
      methanol at room temperature. Electrochemical investigation illustrates the
      electrochemical properties of the title compound. The structure
      (C(62)H(40)Mn(3)N(4)O(15))(n) is monoclinic with a = 14.2304(18), b = 17.019(2),
      c = 25.805(3) A, alpha = gamma = 90, beta = 92.932(2) degrees  and space group
      C2/c.

PMID- 22983151
TI  - Immediate early response genes and cell transformation.
AB  - Cancer has been described as not one disease, but several, each with unique
      characteristics, symptoms, prognostics and outcomes. Underlying this complexity
      is a differential expression of genes, leading to a motley of phenotypes which
      orchestrate the hallmarks of cancer. The idea of treating, suppressing or even
      preventing all forms of cancer with a single form of therapy seems untenable
      given the complexities of these gene expression profiles. However, recent
      advances in the study of immediate early genes, a family of genes that are
      rapidly and transiently upregulated following an external stimulus such as growth
      factors, hormones or stress, and their ubiquitous involvement in regulating
      oncogenomic responses may lend itself to new and unique therapies. At the very
      least, understanding and targeting immediate early gene expression and function
      remains an untapped area in cancer prevention research, and could very well
      provide new resources in cancer treatment and new perspectives in directed cancer
      suppression. In this review, we will discuss the critical role immediate early
      genes play in cancer progression, and provide specific examples of immediate
      early gene function and inhibition.

PMID- 22983152
TI  - New targets and approaches in osteosarcoma.
AB  - Osteosarcoma is the most common primary tumor of bone. Approximately 2/3 of
      patients who present with localized osteosarcoma can be expected to be cured of
      their disease with surgery and routine chemotherapy. Only 1/3 of patients with
      metastases detectable at presentation will be cured. These survival trends have
      stagnated over the past 20 years using conventional chemotherapy. New agents need
      to be rationally investigated to strive for improvement in the survival of
      patients diagnosed with osteosarcoma. This manuscript will review the rationale
      for conventional chemotherapy used in the treatment of osteosarcoma, as well as
      agents in varying stages of development that may have promise for treatment in
      the future.

PMID- 22983153
TI  - Endothelial function, uterine perfusion and central flow in pregnancies
      complicated by Preeclampsia.
AB  - BACKGROUND: The physiopathology of Preeclampsia (PE) is characterized by a
      deficiency in the process of placentation, systemic endothelial dysfunction and
      Central Nervous System (CNS) hyperflow. From a clinical point of view, it would
      be interesting to determine the occurrence of these phenomena before the onset of
      clinical manifestations of the disease, raising the possibility of new methods
      for predicting PE. OBJECTIVE: Compare the process of placentation, endothelial
      function and CNS hyperflow in pregnant women at high risk for the development of
      PE who subsequently developed or not the syndrome. METHODS: A total of 74
      pregnant women underwent the Flow-Mediated Dilation (FMD) of the brachial artery,
      Doppler study of uterine and ophthalmic arteries for the assessment of
      endothelial function, process of placentation and central hyperflow,
      respectively. The examinations were performed between 24 and 28 weeks of
      gestation and were followed until the postpartum period for data collection.
      RESULTS: Fifteen patients had PE and 59 remained normotensive until the
      puerperium. Patients who subsequently developed PE had between 24 and 28 weeks of
      gestation, higher pulsatility index of uterine arteries and lower values of FMD
      (p < 0.001 and p = 0.001, respectively). However, there was no difference in the
      values obtained in the resistive index in the ophthalmic artery (p = 0.08).
      CONCLUSION: The data obtained suggest that the deficiency in the process of
      placentation and endothelial dysfunction chronologically precede the clinical
      manifestations of PE, which does not occur with CNS hyperflow.

PMID- 22983154
TI  - Relationship between parathyroid hormone and depression in heart failure.
AB  - BACKGROUND: Depression has been found to be a predictor of rehospitalization and
      mortality in heart failure (HF). Parathyroid hormone (PTH) is a novel promising
      biomarker that can predict hospitalization, functional status and mortality in
      HF. OBJECTIVE: We aimed to investigate the association of depression with serum
      PTH levels in patients with systolic HF. METHODS: A total of consecutive 100
      outpatients with systolic HF having left ventricular ejection fraction (LVEF) <
      40%, were prospectively studied. All patients underwent laboratory tests,
      including brain natriuretic peptide (BNP) and PTH analyses. The patients were
      asked to complete the Beck Depression Inventory- II (BDI). RESULTS: Fifty-one
      patients (51%) were shown to have poor BDI score (BDIS > 18). Patients with poor
      BDI score had significantly higher PTH levels compared to those with good BDIS
      (133 +/- 46 pg/ml vs. 71 +/- 26 pg/ml, p < 0.001). In multivariable logistic
      regression model, PTH level (Odds ratio (OR) = 1.035, p = 0.003), LVEF (OR =
      0.854, p = 0.004), NYHA functional class III/IV (OR = 28.022, p = 0.005), C
      reactive protein (CRP) (OR = 1.088, p = 0.020), and presence of pretibial edema
      (OR = 12.341, p = 0.033) were found to be independent predictors of moderate to
      severe depression after adjustment of other potential confounders. CONCLUSION:
      Systolic HF patients with moderate to severe depression had higher serum levels
      of PTH and CRP, poor functional status and lower LVEF. The association of
      depression with such parameters might explain the contribution of depression to
      hospitalization and mortality in HF.

PMID- 22983155
TI  - Combined 5' UTR RFLP analysis and VP1 sequencing for epidemic investigation of
      enteroviruses.
AB  - Enteroviruses, the main cause of aseptic meningitis, consist of 100 serotypes,
      and many of them have been associated with large outbreaks. In the present study,
      a comparison of RFLP analysis of the 5' untranslated region (5'UTR) and
      sequencing of both the 5'UTR and VP1 regions was conducted for epidemiological
      linkage of 27 clinical enterovirus strains. The clinical enterovirus strains were
      clustered into five restriction profile groups. Even though the restriction
      profile clusters of clinical isolates were not related to those of the respective
      prototype strains, epidemiological relationships between the members of each
      cluster were observed. The restriction profile clusters in the 5'UTR corresponded
      to the phylogenetic clusters in the VP1 genomic region. The incongruence between
      the topology of Gior strain in 5'UTR and VP1 phylogenetic trees indicates a
      recombination event. The proposed RFLP assay in combination with VP1 sequencing
      can offer crucial epidemiological information about the circulating
      enteroviruses.

PMID- 22983156
TI  - Discovery and biological characterization of geranylated RNA in bacteria.
AB  - A general MS-based screen for unusually hydrophobic cellular small molecule-RNA
      conjugates revealed geranylated RNA in Escherichia coli, Enterobacter aerogenes,
      Pseudomonas aeruginosa and Salmonella enterica var. Typhimurium. The geranyl
      group is conjugated to the sulfur atom in two 5-methylaminomethyl-2-thiouridine
      nucleotides. These geranylated nucleotides occur in the first anticodon position
      of tRNA(Glu)(UUC), tRNA(Lys)(UUU) and tRNA(Gln)(UUG) at a frequency of up to 6.7%
      (~400 geranylated nucleotides per cell). RNA geranylation can be increased or
      abolished by mutation or deletion of the selU (ybbB) gene in E. coli, and
      purified SelU protein in the presence of geranyl pyrophosphate and tRNA can
      produce geranylated tRNA. The presence or absence of the geranyl group in
      tRNA(Glu)(UUC), tRNA(Lys)(UUU) and tRNA(Gln)(UUG) affects codon bias and
      frameshifting during translation. These RNAs represent the first reported
      examples of oligoisoprenylated cellular nucleic acids.

PMID- 22983158
TI  - Cascade functionalization of unsaturated bond-containing polymers using ambident
      agents possessing both nitrile N-oxide and electrophilic functions.
AB  - We developed a powerful and highly reliable cascade functionalization technique
      for constructing sophisticated macromolecular architectures. Central to the
      technique are the ambident agents having combined functions of a nitrile N-oxide
      group and an electrophile. The agents proved capable of facile catalyst- and
      solvent-free functionalization of polymers and further integrations involving
      cross-linking.

PMID- 22983157
TI  - The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK.
AB  - Liver kinase B1 (LKB1) has important roles in governing energy homeostasis by
      regulating the activity of the energy sensor kinase AMP-activated protein kinase
      (AMPK). The regulation of LKB1 function, however, is still poorly understood.
      Here we demonstrate that the orphan nuclear receptor Nur77 binds and sequesters
      LKB1 in the nucleus, thereby attenuating AMPK activation. This Nur77 function is
      antagonized by the chemical compound ethyl 2-[2,3,4-trimethoxy-6-(1
      octanoyl)phenyl]acetate (TMPA), which interacts with Nur77 with high affinity and
      at specific sites. TMPA binding of Nur77 results in the release and shuttling of
      LKB1 to the cytoplasm to phosphorylate AMPKalpha. Moreover, TMPA effectively
      reduces blood glucose and alleviates insulin resistance in type II db/db and high
      fat diet- and streptozotocin-induced diabetic mice but not in diabetic
      littermates with the Nur77 gene knocked out. This study attains a mechanistic
      understanding of the regulation of LKB1-AMPK axis and implicates Nur77 as a new
      and amenable target for the design and development of therapeutics to treat
      metabolic diseases.

PMID- 22983159
TI  - Pulmonary hypertension in systemic lupus erythematosus: a systematic review and
      analysis of 642 cases in Chinese population.
AB  - Pulmonary hypertension (PH) is an increasingly recognized complication of
      systemic lupus erythematosus (SLE). To develop a more comprehensive understanding
      of the clinical and pathological characteristics of pulmonary hypertension
      associated with systemic lupus erythematosus (PH/SLE) in the Chinese population,
      a systematic review of the literature up to 2012 was conducted. Six hundred and
      forty-two Chinese PH/SLE cases from 22 studies were identified as well documented
      and further analyzed. Transthoracic echocardiography (TTE), X-ray,
      electrocardiogram and right heart catheterization (RHC) were performed to
      diagnose PH in SLE patients. The mean age of subjects was 35.5 years, the male to
      female ratio was 1:14, and the mean duration of SLE when PH was diagnosed was
      10.7 years. The prevalence of PH in SLE was 2.8-23.3 %. Symptoms were usually
      nonspecific, and the observed clinical characteristics include Raynaud's
      phenomenon (41.4 %), serous effusion (27.7 %), positive RNP (51.5 %) and positive
      ACL (46.6 %). Gold standard RHC is strongly recommended, especially for those who
      had resting pulmonary arterial systolic pressure >30 mmHg on TTE with the
      aforementioned clinical characteristics. Corticosteroids, immunosuppressants and
      vasodilators were the most common medications employed in treatment. Early
      identification and standard PH treatment with intensive SLE treatment can improve
      the prognosis.

PMID- 22983161
TI  - Keratinocyte-based cell assays: their potential pitfalls.
AB  - As an in vitro model system, patient-derived epidermolysis bullosa simplex
      keratinocytes have had an immense impact on what we know today about keratin
      filament function and their role in disease development. In the absence of gene
      therapy, screening compound libraries for new or better drugs is another approach
      to improve existing treatments for genodermatoses. However in this study, we
      report of the potential pitfalls when using this type of cell lines as a
      "reporter" system. When cell lines with different genetic backgrounds are being
      used in cell-based assays, the greatest obstacle is to determine the most
      appropriate culture conditions (i.e., the composition of medium, number of cells
      plated and number of days in culture). We demonstrate how culture conditions can
      greatly interfere with the cellular response in cell-based assays (cell
      proliferation, metabolic activity and migration), potentially also giving rise to
      misleading data.

PMID- 22983162
TI  - High-throughput fragment screening by affinity LC-MS.
AB  - Fragment screening, an emerging approach for hit finding in drug discovery, has
      recently been proven effective by its first approved drug, vemurafenib, for
      cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon
      resonance, and isothemal titration calorimetry, with their own pros and cons,
      have been employed for screening fragment libraries. As an alternative approach,
      screening based on high-performance liquid chromatography separation has been
      developed. In this work, we present weak affinity LC/MS as a method to screen
      fragments under high-throughput conditions. Affinity-based capillary columns with
      immobilized thrombin were used to screen a collection of 590 compounds from a
      fragment library. The collection was divided into 11 mixtures (each containing 35
      to 65 fragments) and screened by MS detection. The primary screening was
      performed in <4 h (corresponding to >3500 fragments per day). Thirty hits were
      defined, which subsequently entered a secondary screening using an active site
      blocked thrombin column for confirmation of specificity. One hit showed selective
      binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM
      range. This study shows that affinity LC/MS is characterized by high throughput,
      ease of operation, and low consumption of target and fragments, and therefore it
      promises to be a valuable method for fragment screening.

PMID- 22983163
TI  - Development of a high-throughput cell-based assay for identification of IL-17
      inhibitors.
AB  - Human interleukin 17 (IL-17) is a proinflammatory cytokine derived mainly from
      activated T cells. Extensive evidence points to a significant role of IL-17 in
      many autoimmune and infectious diseases, as well as tumorigenesis and transplant
      rejection, and suggests that targeting IL-17 could be a promising therapeutic
      strategy. Robust cell-based assays would thus be essential for lead
      identification and the optimization of therapeutic candidates. Herein, we report
      a well-characterized two-step assay, consisting of (a) in vitro activation and
      stimulation of CD4(+) T lymphocytes by a defined complex of antibodies and
      cytokines, leading to T helper 17 (Th17) cell differentiation and IL-17
      production, and (b) IL-17 quantification in cell supernatants using a homogeneous
      time-resolved fluorescence (HTRF) assay. The system was optimized for and shown
      to be reliable in high-throughput compatible 96- and 384-well plate formats. The
      assay is robust (Z' > 0.5) and simple to perform, yields a stable response, and
      allows for sufficient discrimination of positive (IL-17-producing cells) and
      negative controls (uninduced cells). The assay was validated by performing dose
      response testing of rapamycin and cyclosporine A, which had previously been
      reported to inhibit IL-17, and determining, for the first time, their in vitro
      potencies (IC(50)s of 80 +/- 23 pM and 223 +/- 52 nM, respectively). Also, IKK
      16, a selective small-molecule inhibitor of IkappaB kinase, was found to inhibit
      IL-17 production, with an IC(50) of 315 +/- 79 nM.

PMID- 22983160
TI  - Autophagy and neuronal cell death in neurological disorders.
AB  - Autophagy is implicated in the pathogenesis of major neurodegenerative disorders
      although concepts about how it influences these diseases are still evolving. Once
      proposed to be mainly an alternative cell death pathway, autophagy is now widely
      viewed as both a vital homeostatic mechanism in healthy cells and as an important
      cytoprotective response mobilized in the face of aging- and disease-related
      metabolic challenges. In Alzheimer's, Parkinson's, Huntington's, amyotrophic
      lateral sclerosis, and other diseases, impairment at different stages of
      autophagy leads to the buildup of pathogenic proteins and damaged organelles,
      while defeating autophagy's crucial prosurvival and antiapoptotic effects on
      neurons. The differences in the location of defects within the autophagy pathway
      and their molecular basis influence the pattern and pace of neuronal cell death
      in the various neurological disorders. Future therapeutic strategies for these
      disorders will be guided in part by understanding the manifold impact of
      autophagy disruption on neurodegenerative diseases.

PMID- 22983164
TI  - A rapid screening for cytochrome P450 catalysis on new chemical entities:
      cytochrome P450 BM3 and 1,2,5-oxadiazole derivatives.
AB  - This work presents the validation of a rapid screening procedure for the
      catalysis of cytochrome P450 on new chemical entities. The assay is tested on the
      prototypical, catalytically self-sufficient and soluble cytochrome P450 BM3 from
      Bacillus megaterium that shares a high degree of homology with mammalian
      counterparts. The so-called alkali assay developed in our laboratory is validated
      here also by product formation and molecular modeling on a number of derivatives
      sharing the molecular scaffold of the 1,2,5-oxadiazole ring, a class of molecules
      very different from the long-chain fatty acids known to be oxidized by cytochrome
      P450 BM3. The alkali assay reveals the ability of this cytochrome to oxidize
      NADPH in the presence of nine out of thirteen 1,2,5-oxadiazole derivatives
      tested. The enzyme shows high affinity and coupling efficiencies when incubated
      with four 1,2,5-oxadiazole derivatives. The presence of oxidation products
      deriving from catalysis was also confirmed by high-performance liquid
      chromatography (HPLC). Molecular docking suggests that a key factor for the 1,2,5
      oxadiazole derivatives to enter the active site and induce catalysis is the
      presence of the -SO(2) moiety bridging the 1,2,5-oxadiazole and phenyl rings.
      These data indicate that the alkali assay is able to quickly and cheaply detect
      the recognition of new substrates by cytochrome P450. The assay is not intended
      to substitute HPLC-mass spectrometry analysis, but it is a preliminary screening
      that allows elimination of obvious nonsubstrates from the start.

PMID- 22983165
TI  - A phenotypic assay to identify Chikungunya virus inhibitors targeting the
      nonstructural protein nsP2.
AB  - Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen responsible for an
      acute infection of abrupt onset, characterized by high fever, polyarthralgia,
      myalgia, headaches, chills, and rash. In 2006, CHIKV was responsible for an
      epidemic outbreak of unprecedented magnitude in the Indian Ocean, stressing the
      need for therapeutic approaches. Since then, we have acquired a better
      understanding of CHIKV biology, but we are still missing active molecules against
      this reemerging pathogen. We recently reported that the nonstructural nsP2
      protein of CHIKV induces a transcriptional shutoff that allows the virus to block
      cellular antiviral response. This was demonstrated using various luciferase-based
      reporter gene assays, including a trans-reporter system where Gal4 DNA binding
      domain is fused to Fos transcription factor. Here, we turned this assay into a
      high-throughput screening system to identify small molecules targeting nsP2
      mediated shutoff. Among 3040 molecules tested, we identified one natural compound
      that partially blocks nsP2 activity and inhibits CHIKV replication in vitro. This
      proof of concept suggests that similar functional assays could be developed to
      target other viral proteins mediating a cellular shutoff and identify innovative
      therapeutic molecules.

PMID- 22983166
TI  - Development of a fluorescence intensity assay for the mitotic serine/threonine
      protein kinase Aurora-A.
AB  - The Aurora kinases are a group of serine/threonine protein kinases that regulate
      key steps during mitosis, and deregulation of these proteins (e.g., by gene
      amplification or overexpression) has been linked to a wide variety of tumor
      types. Thus, Aurora-A and Aurora-B have been intensely studied as targets for
      anticancer therapy and are now clinically validated targets. Here we report on
      the development of a novel fluorescence intensity binding assay for Aurora-A
      kinase inhibitors using a fluorescently labeled probe compound that shows
      intramolecular quenching when unbound but exhibits a dramatic increase in
      fluorescence when bound to Aurora-A.

PMID- 22983167
TI  - Molecular characterisation of Anisakidae larvae from fish in Adriatic Sea.
AB  - In the present study, anisakids from: tuna (Thunnus thynnus) fattened in the
      Croatian farm in middle Adriatic Sea, three different feral fish species caught
      near tuna farm (Trachurus trachurus, Scomber japonicus and Oblada melanura) and
      fish marketed in Croatia (T. trachurus) were analysed by morphology and molecular
      methods. Larvae were identified to the species level by PCR restriction fragment
      length polymorphism and characterised by sequencing of nuclear (internal
      transcribed spacer) and mitochondrial (cytochrome c oxidase subunit 2) markers.
      The results revealed diverse Anisakidae community consisting of: Anisakis
      pegreffi, Anisakis simplex (s.s.), Anisakis typica and Hysterothylacium aduncum.
      This is the first report of A. typica in Adriatic Sea, and also the first record
      of this species in T. thynnus as host in Mediterranean Sea. Molecular
      identification of H. aduncum found in co-infection with Anisakis larvae type I
      expands our knowledge of the occurrence of these taxa in the Adriatic Sea.
      Zoonotic Anisakidae worms found in fish from the Adriatic Sea could represent a
      risk to acquire parasitic infection/allergies in Croatia.

PMID- 22983169
TI  - Characterization and deposition of various light-harvesting antenna complexes by
      electrospray atomization.
AB  - Photosynthetic organisms have light-harvesting complexes that absorb and transfer
      energy efficiently to reaction centers. Light-harvesting complexes (LHCs) have
      received increased attention in order to understand the natural photosynthetic
      process and also to utilize their unique properties in fabricating efficient
      artificial and bio-hybrid devices to capture solar energy. In this work, LHCs
      with different architectures, sizes, and absorption spectra, such as chlorosomes,
      Fenna-Matthews-Olson (FMO) protein, LH2 complex, and phycobilisome have been
      characterized by an electrospray-scanning mobility particle-sizer system (ES
      SMPS). The size measured by ES-SMPS for FMO, chlorosomes, LH2, and phycobilisome
      were 6.4, 23.3, 9.5, and 33.4 nm, respectively. These size measurements were
      compared with values measured by dynamic light scattering and those reported in
      the literature. These complexes were deposited onto a transparent substrate by
      electrospray deposition. Absorption and fluorescence spectra of the deposited
      LHCs were measured. It was observed that the LHCs have light absorption and
      fluorescence spectra similar to that in solution, demonstrating the viability of
      the process.

PMID- 22983168
TI  - Prevalence and genotypes of Giardia duodenalis from dogs in Spain: possible
      zoonotic transmission and public health importance.
AB  - The prevalence of Giardia duodenalis was determinate in faecal samples from dogs
      and cats in Madrid, Spain and molecular characterisation of isolates. A total of
      604 and 144 faecal samples from dogs and cats, respectively, were analysed by
      routine coprological methods. The prevalence of G. duodenalis was 16.4 % (99/604)
      in dogs and 4.2 % (6/144) in cats. Sixty-four G. duodenalis isolates (63 from
      dogs and 1 from a cat) were characterised using glutamate dehydrogenase and beta
      giardin genes by PCR-RFLP. The single cat sample showed a mixed infection by
      assemblages A + F. The assemblages found in the dog samples were A, B, C, D and
      E, both as single and as mixed infections. The zoonotic assemblages A and B were
      found in 56 (88.8 %) G. duodenalis-positive samples with 15.9 % of samples having
      assemblage A (10/63) and 73 % of samples with assemblage B (46/63), indicating
      high potential zoonotic risk and public health significance.

PMID- 22983170
TI  - Differential immuno-kinetic assays of allergen-specific binding for peanut
      allergy serum analysis.
AB  - A label-free nanoparticle array platform has been used to detect total peanut
      allergen-specific binding from whole serum of patients suffering from peanut
      allergy. The serum from 10 patients was screened against a four-allergen panel of
      cat and dog dander, dust mite and peanut allergen protein Ara h1. The IgE and IgG
      contributions to the total specific-binding protein load to Ara h1 were
      identified using two secondary IgG- and IgE-specific antibodies and were found to
      contribute less than 50 % of the total specific protein load. The total mass of
      IgE, IgE and the unresolved specific-binding protein DeltasBP for Ara h1 provides
      a new serum profile for high-RAST-grade patients 5 and 6 with the IgG/IgE ratio
      of 4 +/- 2 and DeltasBP/IgE ratio of 17 +/- 11, neither of which is protective
      for the small patient cohort.

PMID- 22983172
TI  - Biolistic delivery of voltage-sensitive dyes for fast recording of membrane
      potential changes in individual neurons in rat brain slices.
AB  - Optical recording of membrane potential changes with fast voltage-sensitive dyes
      (VSDs) in neurons is one of the very few available methods for studying the
      generation and propagation of electrical signals to the distant compartments of
      excitable cells. The more lipophilic is the VSD, the better signal-to-noise ratio
      of the optical signal can be achieved. At present there are no effective ways to
      deliver water-insoluble dyes into the membranes of live cells. Here, we report a
      possibility to stain individual live neurons with highly lipophilic VSDs in acute
      brain slices using biolistic delivery. We tested four ANEP-based VSDs with
      different lipophilic properties and showed their ability to stain single neurons
      in a slice area of up to 150 MUm in diameter after being delivered by a biolistic
      apparatus. In the slices of neocortex and hippocampus, the two most lipophilic
      dyes, di-8-ANEPPS and di-12-ANEPPQ, showed cell-specific loading and Golgi-like
      staining patterns with minimal background fluorescence. Simultaneous patch-clamp
      and optical recording of biolistically stained neurons demonstrated a good match
      of optical and electrical signals both for spontaneous APs (action potentials)
      and stimulus-evoked events. Our results demonstrate the high efficiency of a fast
      and targeted method of biolistic delivery of lipophilic VSDs for optical signals
      recording from mammalian neurons in vitro.

PMID- 22983173
TI  - A comparison between automated detection methods of high-frequency oscillations
      (80-500 Hz) during seizures.
AB  - High-frequency oscillations (HFOs, ripples: 80-200 Hz, fast ripples: 250-500 Hz)
      recorded from the epileptic brain are thought to reflect abnormal network-driven
      activity. They are also better markers of seizure onset zones compared to
      interictal spikes. There is thus an increasing number of studies analysing HFOs
      in vitro, in vivo and in the EEG of human patients with refractory epilepsy.
      However, most of these studies have focused on HFOs during interictal events or
      at seizure onset, and few have analysed HFOs during seizures. In this study, we
      are comparing three different automated methods of HFO detection to two methods
      of visual analysis, during the pre-ictal, ictal and post-ictal periods on
      multiple channels using the rat pilocarpine model of temporal lobe epilepsy. The
      first method (method 1) detected HFOs using the average of the normalised period,
      the second (method 2) detected HFOs using the average of the normalised period in
      1s windows and the third (method 3) detected HFOs using the average of a
      reference period before seizure onset. Overall, methods 2 and 3 showed higher
      sensitivity compared to method 1. When dividing the analysed traces in pre-,
      ictal and post-ictal periods, method 3 showed the highest sensitivity during the
      ictal period compared to method 1, while method 2 was not significantly different
      from method 1. These findings suggest that method 3 could be used for automated
      and reliable detection of HFOs on large data sets containing multiple channels
      during the ictal period.

PMID- 22983174
TI  - Gene transfer of Chlorella vulgaris n-3 fatty acid desaturase optimizes the fatty
      acid composition of human breast cancer cells.
AB  - Chlorella vulgaris has the gene of n-3 fatty acid desaturase (CvFad3), which can
      synthesize the precursor of n-3 polyunsaturated fatty acids (PUFAs) or convert n
      6 to n-3 PUFAs. The objective of the present study was to examine whether the
      CvFad3 gene from C. vulgaris can be functionally and efficiently expressed in
      human breast cancer cells and whether its expression can exert a significant
      effect on cell fatty acid composition. We inserted the CvFad3 gene into the
      plasmid pEGFP-C3 to construct the eukaryotic expression vector pEGFP-C3-n-3 and
      to express the n-3 Fad gene in human breast cancer cells (MCF-7 cells).
      Transfection of MCF-7 cells with the recombinant vector resulted in a high
      expression of n-3 fatty acid desaturase. Lipid analysis indicated that the ratio
      of n-6/n-3 PUFAs was decreased from 6:1 in the control cells to about 1:1 in the
      cells expressing the n-3 fatty acid desaturase. Accordingly, the CvFad3 gene
      significantly decreased the ratio of n-6/n-3 PUFAs of the MCF-7 cell membrane.
      The expression of the CvFad3 gene can decrease cell proliferation and promote
      cell apoptosis. This study demonstrates that the CvFad3 gene can dramatically
      balance the ratio of n-6/n-3 PUFAs and may provide an effective approach to the
      modification of the fatty acid composition of mammalian cells, also providing a
      basis for potential applications of its transfer in experimental and clinical
      settings.

PMID- 22983175
TI  - Effect of the ketamine/xylazine anesthetic on the auditory brainstem response of
      adult gerbils.
AB  - The auditory brainstem response (ABR) is a test widely used to assess the
      integrity of the brain stem. Although it is considered to be an auditory-evoked
      potential that is influenced by the physical characteristics of the stimulus,
      such as rate, polarity and type of stimulus, it may also be influenced by the
      change in several parameters. The use of anesthetics may adversely influence the
      value of the ABR wave latency. One of the anesthetics used for e ABR assessment,
      especially in animal research, is the ketamine/xylazine combination. Our
      objective was to determine the influence of the ketamine/xylazine anesthetic on
      the ABR latency values in adult gerbils. The ABRs of 12 adult gerbils injected
      with the anesthetic were collected on three consecutive days, or a total of six
      collections, namely: pre-collection and A, B, C, D, and E collections. Before
      each collection the gerbil was injected with a dose of ketamine (100
      mg/kg)/xylazine (4 mg/kg). For the capture of the ABR, 2000 click stimuli were
      used with rarefaction polarity and 13 stimuli per second, 80 dBnHL intensity and
      in-ear phones. A statistically significant difference was observed in the latency
      of the V wave in the ABR of gerbils in the C and D collections compared to the
      pre-, A and E collections, and no difference was observed between the pre-, A, B,
      and E collections. We conclude that the use of ketamine/xylazine increases the
      latency of the V wave of the ABR after several doses injected into adult gerbils;
      thus clinicians should consider the use of this substance in the assessment of
      ABR.

PMID- 22983176
TI  - Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic
      liver disease in Wistar rats.
AB  - Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD).
      We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight)
      for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in
      male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile
      duct-ligated animals previously treated with pamidronate before and 1 month after
      surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month
      after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery.
      Immunohistochemical expression of IGF-I and GH receptor was determined in the
      proximal growth plate cartilage of the left tibia. Histomorphometric analysis was
      performed in the right tibia and the right femur was used for biomechanical
      analysis. Bone material volume over tissue volume (BV/TV) was significantly
      affected by CCLD (Sham = 18.1 +/- 3.2 vs Bi = 10.6 +/- 2.2%) and pamidronate
      successfully increased bone volume. However, pamidronate administered in a
      preventive regimen presented no additional benefit on bone volume compared to
      secondary treatment (BV/TV: Pr = 39.4 +/- 12.0; Tr = 41.2 +/- 12.7%). Moreover,
      the force on the momentum of fracture was significantly reduced in Pr rats (Sham
      = 116.6 +/- 23.0; Bi = 94.6 +/- 33.8; Pr = 82.9 +/- 22.8; Tr = 92.5 +/- 29.5 N; P
      < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone
      histomorphometric parameters and pamidronate was highly effective in increasing
      bone mass in CCLD; however, preventive therapy with pamidronate has no advantage
      regarding bone fragility.

PMID- 22983177
TI  - Impairment of the hematological response and interleukin-1beta production in
      protein-energy malnourished mice after endotoxemia with lipopolysaccharide.
AB  - The objectives of this study were to determine if protein-energy malnutrition
      (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the
      interleukin-1beta (IL-1beta) production, leukocyte migration, and blood leukocyte
      expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N
      = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20%
      protein in the control group (N = 30). The total cellularity of blood, bone
      marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus
      indicated reduced number of total cells in all compartments studied and different
      kinetics of migration in malnourished animals. The in vitro migration assay
      showed reduced capacity of migration after the LPS stimulus in malnourished
      animals (45.7 +/- 17.2 x 10(4) cells/mL) compared to control (69.6 +/- 7.1 x
      10(4) cells/mL, P <= 0.05), but there was no difference in CD11a/CD18 expression
      on the surface of blood leukocytes. In addition, the production of IL-1beta in
      vivo after the LPS stimulus (180.7 pg.h-1.mL-1), and in vitro by bone marrow and
      spleen cells (41.6 +/- 15.0 and 8.3 +/- 4.0 pg/mL) was significantly lower in
      malnourished animals compared to control (591.1 pg.h-1.mL-1, 67.0 +/- 23.0 and
      17.5 +/- 8.0 pg/mL, respectively, P <= 0.05). The reduced expression of IL-1beta,
      together with the lower number of leukocytes in the central and peripheral
      compartments, different leukocyte kinetics, and reduced leukocyte migration
      capacity are factors that interfere with the capacity to mount an adequate immune
      response, being partly responsible for the immunodeficiency observed in PEM.

PMID- 22983178
TI  - Participation of cannabinoid receptors in peripheral nociception induced by some
      NSAIDs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to
      control inflammatory pain. Several peripheral antinociceptive mechanisms have
      been described, such as opioid system and NO/cGMP/KATP pathway activation. There
      is evidence that the cannabinoid system can also contribute to the in vivo
      pharmacological effects of ibuprofen and indomethacin. However, there is no
      evidence of the involvement of the endocannabinoid system in the peripheral
      antinociception induced by NSAIDs. Thus, the aim of this study was to investigate
      the participation of the endocannabinoid system in the peripheral antinociceptive
      effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g;
      N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl)
      injection of prostaglandin E2 (PGE2, 2 MUg/paw) in the rat's hindpaw and measured
      by the paw pressure test 3 h after injection. The weight in grams required to
      elicit a nociceptive response, paw flexion, was determined as the nociceptive
      threshold. The hyperalgesia was calculated as the difference between the
      measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3
      +/- 4.505 g). AM-251 (80 MUg/paw) and AM-630 (100 MUg/paw) were used as CB1 and
      CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 MUg
      dipyrone (mean = 5.825 +/- 2.842 g), 20 MUg diclofenac (mean = 4.825 +/- 3.850 g)
      and 40 MUg indomethacin (mean = 6.650 +/- 3.611 g) elicited a local peripheral
      antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid
      antagonist to dipyrone (mean = 5.00 +/- 0.9815 g), diclofenac (mean = 2.50 +/-
      0.8337 g) and indomethacin (mean = 6.650 +/- 4.069 g) or CB2 cannabinoid
      antagonist to dipyrone (mean = 1.050 +/- 6.436 g), diclofenac (mean = 6.675 +/-
      1.368 g) and indomethacin (mean = 2.85 +/- 5.01 g). Thus, cannabinoid receptors
      do not seem to be involved in the peripheral antinociceptive mechanism of the
      NSAIDs dipyrone, diclofenac and indomethacin.

PMID- 22983180
TI  - Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat
      experimental tuberculosis.
AB  - In the last several years, the use of dendritic cells has been studied as a
      therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides
      or full-length protein, or they can be transfected with DNA or RNA. However,
      comparative studies suggest that transfecting dendritic cells with messenger RNA
      (mRNA) is superior to other antigen-loading techniques in generating
      immunocompetent dendritic cells. In the present study, we evaluated a new
      therapeutic strategy to fight tuberculosis using dendritic cells and macrophages
      transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells
      transfected with Hsp65 mRNA exhibit a higher level of expression of co
      stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory
      properties. We also demonstrated that spleen cells obtained from animals
      immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to
      generate a mixed Th1/Th2 response with production not only of IFN-gamma but also
      of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65
      mRNA-transfected macrophages were able to produce only IL-5. When mice were
      infected with Mycobacterium tuberculosis and treated with antigen-presenting
      cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect
      any decrease in the lung bacterial load or any preservation of the lung
      parenchyma, indicating the inability of transfected cells to confer curative
      effects against tuberculosis. In spite of the lack of therapeutic efficacy, this
      study reports for the first time the use of antigen-presenting cells transfected
      with mRNA in experimental tuberculosis.

PMID- 22983181
TI  - Pediatric pain: prevalence, assessment, and management in a teaching hospital.
AB  - The goal of this study was to examine the prevalence, assessment and management
      of pediatric pain in a public teaching hospital. The study sample consisted of
      121 inpatients (70 infants, 36 children, and 15 adolescents), their families, 40
      physicians, and 43 nurses. All participants were interviewed except infants and
      children who could not communicate due to their clinical status. The interview
      included open-ended questions concerning the inpatients' pain symptoms during the
      24 h preceding data collection, as well as pain assessment and
      pharmacological/non-pharmacological management of pain. The data were obtained
      from 100% of the eligible inpatients. Thirty-four children/adolescents (28%)
      answered the questionnaire and for the other 72% (unable to communicate), the
      family/health professional caregivers reported pain. Among these 34 persons, 20
      children/adolescents reported pain, 68% of whom reported that they received
      pharmacological intervention for pain relief. Eighty-two family caregivers were
      available on the day of data collection. Of these, 40 family caregivers (49%) had
      observed their child's pain response. In addition, 74% reported that the
      inpatients received pharmacological management. Physicians reported that only 38%
      of the inpatients exhibited pain signs, which were predominantly acute pain
      detected during clinical procedures. They reported that 66% of patients received
      pharmacological intervention. The nurses reported pain signs in 50% of the
      inpatients, which were detected during clinical procedures. The nurses reported
      that pain was managed in 78% of inpatients by using pharmacological and/or non
      pharmacological interventions. The findings provide evidence of the high
      prevalence of pain in pediatric inpatients and the under-recognition of pain by
      health professionals.

PMID- 22983182
TI  - In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen
      membranes treated with hyaluronic acid for cell therapy and tissue regeneration.
AB  - Support structures for dermal regeneration are composed of biodegradable and
      bioresorbable polymers, animal skin or tendons, or are bacteria products. The use
      of such materials is controversial due to their low efficiency. An important area
      within tissue engineering is the application of multipotent mesenchymal stromal
      cells (MSCs) to reparative surgery. The combined use of biodegradable membranes
      with stem cell therapy may lead to promising results for patients undergoing
      unsuccessful conventional treatments. Thus, the aim of this study was to test the
      efficacy of using membranes composed of anionic collagen with or without the
      addition of hyaluronic acid (HA) as a substrate for adhesion and in vitro
      differentiation of bone marrow-derived canine MSCs. The benefit of basic
      fibroblast growth factor (bFGF) on the differentiation of cells in culture was
      also tested. MSCs were collected from dog bone marrow, isolated and grown on
      collagen scaffolds with or without HA. Cell viability, proliferation rate, and
      cellular toxicity were analyzed after 7 days. The cultured cells showed uniform
      growth and morphological characteristics of undifferentiated MSCs, which
      demonstrated that MSCs successfully adapted to the culture conditions established
      by collagen scaffolds with or without HA. This demonstrates that such scaffolds
      are promising for applications to tissue regeneration. bFGF significantly
      increased the proliferative rate of MSCs by 63% when compared to groups without
      the addition of the growth factor. However, the addition of bFGF becomes
      limiting, since it has an inhibitory effect at high concentrations in culture
      medium.

PMID- 22983183
TI  - Effect of ATP and 2-oxoglutarate on the in vitro interaction between the NifA GAF
      domain and the GlnB protein of Azospirillum brasilense.
AB  - Azospirillum brasilense is a diazotroph that associates with important
      agricultural crops and thus has potential to be a nitrogen biofertilizer. The A.
      brasilense transcription regulator NifA, which seems to be constitutively
      expressed, activates the transcription of nitrogen fixation genes. It has been
      suggested that the nitrogen status-signaling protein GlnB regulates NifA activity
      by direct interaction with the NifA N-terminal GAF domain, preventing the
      inhibitory effect of this domain under conditions of nitrogen fixation. In the
      present study, we show that an N-terminal truncated form of NifA no longer
      required GlnB for activity and lost regulation by ammonium. On the other hand, in
      trans co-expression of the N-terminal GAF domain inhibited the N-truncated
      protein in response to fixed nitrogen levels. We also used pull-down assays to
      show in vitro interaction between the purified N-terminal GAF domain of NifA and
      the GlnB protein. The results showed that A. brasilense GlnB interacts directly
      with the NifA N-terminal domain and this interaction is dependent on the presence
      of ATP and 2-oxoglutarate.

PMID- 22983184
TI  - Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic
      data and phenotypic features.
AB  - Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly
      manifesting in females. Patients show ocular, facial, cardiac, and dental
      abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR
      gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian
      family with four female members (grandmother, mother and monozygotic female
      twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T
      (p.R1480*). They present high intrafamilial phenotypic variability with special
      regard to cardiac defect and cataract that showed more severe disease expression
      in successive generations. Clinical and radiographic examination of the mother of
      the twins revealed a talon cusp involving the permanent maxillary right central
      incisor. This is the first known report of a talon cusp in OFCD syndrome with a
      novel mutation in the BCOR gene.

PMID- 22983186
TI  - Professor Artur Czyzyk (1927-2012): an excellent doctor, outstanding researcher,
      and cofounder of Polish diabetology.

PMID- 22983185
TI  - Purified and highly aggregated chimeric protein DIIIC-2 induces a functional
      immune response in mice against dengue 2 virus.
AB  - It was previously reported that DIIIC-2 (a fusion protein composed of domain III
      of the envelope protein and the capsid protein from dengue 2 virus), as an
      aggregate antigen from a partially purified preparation, induced a functional
      protective immune response against dengue 2 virus in the mouse encephalitis
      model. In the present work, a purification procedure was developed for DIIIC-2,
      and soluble and aggregated fractions of the purified protein were characterized
      and evaluated in mice. The purification process rendered a protein preparation of
      91 % purity, and the remaining 9 % consisted of fragments and aggregates of the
      same recombinant protein. After the in vitro aggregation process, upon addition
      of oligodeoxynucleotides, 80 % of the protein formed aggregates, whereas 20 %
      remained as soluble protein. An immunological evaluation revealed the proper
      immunogenicity of the aggregated purified protein in terms of induction of
      antiviral and neutralizing antibodies, cell-mediated immunity and protection upon
      dengue 2 virus challenge in the mouse encephalitis model. Based on these results,
      we can assert that the purified protein DIIIC-2 is functional and could be used
      for further scalable steps and preclinical studies in non-human primates.

PMID- 22983187
TI  - Prevention of stroke and systemic embolization in atrial fibrillation: a Canadian
      perspective.
AB  - Atrial fibrillation (AF) has a prevalence of about 1% in the general population,
      but is much more common in the elderly. The annual overall risk of stroke is
      about 4.5% without antithrombotic therapy, but the risk in an individual patient
      varies from under 1% to about 20%, depending on the presence of well-recognized
      risk factors. The risk of stroke, usually followed by major neurological deficit
      or death, is reduced by about two-thirds by oral vitamin K antagonist (VKA)
      therapy and about 20% by aspirin. This risk reduction generally outweighs the
      risk of major hemorrhage caused by oral anticoagulation. New oral anticoagulants
      (dabigatran, rivaroxaban, and apixaban) obviate many of the difficulties
      experienced by patients and doctors in the use of oral VKAs. Comparisons with
      warfarin in recent large randomized clinical trials have demonstrated advantages
      of efficacy and safety, which vary somewhat from one agent to another but all
      offer excellent alternatives to VKAs for stroke prevention. Recent clinical
      practice guidelines recommend these agents as alternatives to VKAs.

PMID- 22983188
TI  - Management of patients who are receiving warfarin or a new oral anticoagulant and
      require urgent or emergency surgery.
AB  - An increasing number of patients are receiving long-term oral anticoagulant
      therapy and the availability of new oral anticoagulants (OACs), which are easier
      to use than warfarin, will further expand the population of anticoagulated
      patients. As a consequence, an increasing number of patients will need
      perioperative anticoagulant management because of elective or nonelective surgery
      or procedures. The perioperative management of such patients is pertinent to a
      broad spectrum of physicians, including anesthesiologists, internists, and
      surgeons. The objectives of this review are to provide a clinically-focused
      background on the pharmacology of warfarin and the new OACs and to suggest
      perioperative anticoagulant management strategies. This review will focus on the
      perioperative management of warfarin and new OACs who require urgent or emergent
      surgery or who require rapid anticoagulant reversal because of ongoing bleeding
      or high bleeding risk.

PMID- 22983189
TI  - Renal involvement in multiple myeloma.
AB  - In this paper, the spectrum of renal involvement in the course of multiple
      myeloma (MM) is discussed. We describe the most important pathophysiological
      mechanisms underlying the development of renal complications observed in MM. In
      particular, we focused on the correlations between morphological changes in the
      kidneys and clinical signs and symptoms. Physicochemical characteristics of light
      chains that are synthesized in excess are critically important in the development
      of different types of renal involvement. It seems that patients with MM should be
      actively treated regardless of the type of lesions because the current methods
      allow to reverse renal lesions and reduce the negative effect of renal damage on
      prognosis in these patients.

PMID- 22983190
TI  - To keep or not to keep: hemodialysis arteriovenous fistula following kidney
      transplantation.

PMID- 22983191
TI  - To close or not to close arteriovenous fistulas in kidney allograft recipients:
      that is the question.

PMID- 22983192
TI  - Molecular mechanisms of cancer cell-cell interactions: cell-cell adhesion
      dependent signaling in the tumor microenvironment.

PMID- 22983193
TI  - Wip1 phosphatase positively modulates dendritic spine morphology and memory
      processes through the p38MAPK signaling pathway.
AB  - Dendritic spine morphology is modulated by protein kinase p38, a mitogen
      activated protein (MAPK), in the hippocampus. Protein p38MAPK is a substrate of
      wip1, a protein phosphatase. The role of wip1 in the central nervous system (CNS)
      has never been explored. Here, we report a novel function of wip1 in dendritic
      spine morphology and memory processes. Wip1 deficiency decreases dendritic spine
      size and density in pyramidal neurons of the hippocampal CA1 region.
      Simultaneously, impairments in object recognition tasks and contextual memory
      occur in wip1 deficient mice, but are reversed in wip1/p38 double mutant mice.
      Thus, our findings demonstrate that wip1 modulates dendritic morphology and
      memory processes through the p38MAPK signaling pathway. In addition to the well
      characterized role of the wip1/p38MAPK in cell death and differentiation, we
      revealed the novel contribution of wip1 to cognition and dendritic spine
      morphology, which may suggest new approaches to treating neurodegenerative
      disorders.

PMID- 22983194
TI  - Functional significance of periostin in excisional skin repair: is the devil in
      the detail?
AB  - In the past year, three papers have been published exploring the role of the
      matricellular protein periostin in excisional skin repair. These papers all show
      a delay in wound closure and the kinetics of this delay are strikingly similar
      across the three reports. The similarities between these papers end, however,
      when each investigates the mechanism through which periostin influences skin
      repair. Three proposed mechanisms have been identified: (1) myofibroblast
      differentiation, (2) keratinocyte proliferation and (3) fibroblast proliferation
      and migration. The aim of this commentary is to compare and contrast the three
      studies performed to date in an attempt to decipher the role of periostin in the
      repair of full-thickness skin wounds.

PMID- 22983195
TI  - N-cadherin expression level as a critical indicator of invasion in non-epithelial
      tumors.
AB  - Cancer cell dissemination away from the primary tumor and their ability to form
      metastases remain the major causes of death from cancer. Understanding the
      molecular mechanisms triggering this event could lead to the design of new cancer
      treatments. The establishment and the maintenance of tissue architecture depend
      on the coordination of cell behavior within this tissue. Cell-cell interactions
      must form adhesive structures between neighboring cells while remaining highly
      dynamic to allow and control tissue renewal or remodeling. Among intercellular
      junctions, cadherin-based adherens junctions mediate strong physical interactions
      and transmit information from the cell microenvironment to the cytoplasm.
      Disruption of these cell-cell contacts perturbs the polarity of epithelial
      tissues leading to their disorganization and ultimately to aggressive carcinomas.
      In non-epithelial tissues, the role of cadherins in the development of cancer is
      still debated. We recently found that downregulation of N-cadherin in malignant
      glioma-the most frequent primary brain tumor-results in cell polarization defects
      leading to abnormal motile behavior with increased cell speed and decreased
      persistence in directionality. Re-expression of N-cadherin in glioma cells
      restores cell polarity and limits glioma cell migration, providing a potential
      therapeutic tool for diffuse glioma.

PMID- 22983196
TI  - IGF2BP1: a post-transcriptional "driver" of tumor cell migration.
AB  - The oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA binding protein 1) controls
      the cytoplasmic fate of specific target mRNAs including ACTB and CD44. During
      neural development, IGF2BPs promote neurite protrusion and the migration of
      neuronal crest cells. In tumor-derived cells, IGF2BP1 enhances the formation of
      lamellipodia and invadopodia. Accordingly, the de novo synthesis of IGF2BP1
      observed in primary malignancies was reported to correlate with increased
      metastasis and an overall poor prognosis. However, if and how the protein
      enhances metastasis remains controversial. In recent studies, we reveal that
      IGF2BP1 promotes the directed migration of tumor-derived cells in vitro by
      controlling the expression of MAPK4 and PTEN. The IGF2BP1-facilitated inhibition
      of MAPK4 mRNA translation interferes with MK5-directed phosphorylation of the
      heat shock protein 27 (HSP27). This limits G-actin sequestering by phosphorylated
      HSP27, enhances cell adhesion and elevates the velocity of tumor cell migration.
      Concomitantly, IGF2BP1 promotes the expression of PTEN by interfering with PTEN
      mRNA turnover. This results in a shift of cellular PtdIns(3,4,5)P 3/PtdIns(4,5)P
      2 ratios and enhances RAC1-dependent cell polarization which finally promotes the
      directionality of tumor cell migration. These findings identify IGF2BP1 as a
      potent oncogenic factor that regulates the adhesion, migration and invasiveness
      of tumor cells by modulating intracellular signaling.

PMID- 22983197
TI  - Integrin adhesions: who's on first? What's on second? Connections between FAK and
      talin.
AB  - Cell migration requires the coordination of adhesion site assembly and turnover.
      Canonical models for nascent adhesion formation postulate that integrin binding
      to extracellular matrix (ECM) proteins results in the rapid recruitment of
      cytoskeletal proteins such as talin and paxillin to integrin cytoplasmic domains.
      It is thought that integrin-talin clusters recruit and activate tyrosine kinases
      such as focal adhesion kinase (FAK). However, the molecular connections of this
      linkage remain unresolved. Our recent findings support an alternative model
      whereby FAK recruits talin to new sites of beta1 integrin-mediated adhesion in
      mouse embryonic fibroblasts and human ovarian carcinoma cells. This is dependent
      on a direct binding interaction between FAK and talin and occurs independently of
      direct talin binding to beta1 integrin. Herein, we discuss differences between
      nascent and mature adhesions, interactions between FAK, talin and paxillin,
      possible mechanisms of FAK activation and how this FAK-talin complex may function
      to promote cell motility through increased adhesion turnover.

PMID- 22983199
TI  - Probing electronic coupling between adenine bases in RNA strands from synchrotron
      radiation circular dichroism experiments.
AB  - Circular dichroism spectra (176-330 nm) of RNA adenine oligomers, (rA)(n) (n = 1
      10, 12, 15, and 20), reveal electronic coupling between two bases in short
      strands. The number of interacting bases in long strands is more and larger than
      that reported previously for the corresponding DNA strands.

PMID- 22983198
TI  - Comprehensive analysis of NAC domain transcription factor gene family in Vitis
      vinifera.
AB  - KEY MESSAGE : Genome-wide identification of grapevine NAC domain genes and
      investigation of their chromosome locations, gene structures, duplication,
      evolution, phylogeny and expression profiles. Grapevine is a widely used fruit
      crop. NAC (NAM, ATAF1/2 and CUC2) domain genes are plant-specific transcription
      factors (TFs) that comprise a conserved NAM domain in the N-terminus. Members of
      this gene family have been reported to contribute to plant development. During
      this study, 74 NAC genes were identified from 12* assembled grapevine genomic
      sequences. The duplication patterns, genomic structures and phylogeny of these 74
      grapevine NAC genes were investigated. To understand the roles of VvNAC during
      grapevine development, their expression profiles in different tissues including
      leaf, tendril, inflorescence, stem, root and veraison berry skin were tested
      using quantitative real-time PCR. Analysis revealed expression diversity of
      various VvNAC genes among different grapevine tissues. To identify candidate
      grapevine NAC genes with a role in response to stress, publicly available
      microarray data were obtained to calculate their expression change under abiotic
      and biotic treatments, with a number of VvNAC genes displaying up-regulation
      after stress induction. Therefore, this study has uncovered more knowledge
      relating to the gene structures, chromosome organizations, evolution, expression
      profiles and functions of VvNAC genes.

PMID- 22983200
TI  - Pulmonary fibrosis in workers exposed to non-asbestiform tremolite asbestos
      minerals.
AB  - BACKGROUND: Studies of the health effects of non-asbestiform asbestos minerals
      remain inconclusive. Nephrite is a type of non-asbestiform tremolite mineral. We
      assessed the risk for pulmonary fibrosis in workers who process nephrite.
      METHODS: A cross-sectional study that included 344 stone workers and their
      families was undertaken in Taiwan in 2010. The diagnostic criteria for pulmonary
      fibrosis included (1) radiographic fibrosis profusion of 1/1 or greater and (2)
      audible lung crackles confirmed by physician. The nephrite samples were analyzed
      using polarized light and transmission electron microscopy combined with selected
      area electron diffraction and energy-dispersive x-ray spectroscopy. RESULTS:
      After excluding 16 subjects with histories of tuberculosis or previous employment
      in metal casting and welding, as well as 23 family members who had not worked in
      the stone industry, we analyzed 305 subjects. Processing nephrite increased the
      risk for pulmonary fibrosis (odds ratio = 2.8 [95% confidence interval = 1.0-9.9]
      and unchanged after adjustment for age and smoking). Bulk sample analyses showed
      that the nephrite is a tremolite mineral composed of both asbestiform and non
      asbestiform components. The cat's-eye nephrite had the highest asbestiform
      fibrous content, and the average length and aspect ratio of elongated mineral
      particles were the highest of all the nephrite types. Compared with workers
      processing other types of nephrite, workers processing cat's-eye nephrite had the
      highest risk for pulmonary fibrosis. CONCLUSION: Processing non-asbestiform
      tremolite mineral may increase the risk for pulmonary fibrosis. Medical
      monitoring is warranted for workers with such exposure.

PMID- 22983201
TI  - Simultaneous preconcentration of copper and mercury in water samples by cloud
      point extraction and their determination by inductively coupled plasma atomic
      emission spectrometry.
AB  - A cloud-point extraction process coupled to ICP-OES by using 3-nitro benzaldehyde
      thiosemicarbazone (3-NBT) as complexing agent was developed for the simultaneous
      preconcentration and determination of copper and mercury in water samples. The
      variables affecting the complexation and extraction steps were optimized. Under
      the optimum conditions (i.e. 1.5*10(-5) mol L(-1) ligand, 0.3% (v/v) Triton X
      114, 55  degrees C equilibrium temperature, incubation time of 30 min) the
      calibration graphs were linear in the range of 5-120 and 10-100 ng mL(-1) with
      enhancement factor of 82.7 and 51.3 for Cu(2+) and Hg(2+), respectively. The
      preconcentration factors were 28.6 in both cases and detection limits were
      obtained 0.48 for Cu and 1.1 ng mL(-1) for Hg. The precisions (R.S.D.%) for five
      replicate determinations at 50 ng mL(-1) of copper and mercury were better than
      1.8% and 3.2%, respectively. The accuracy of the proposed method is validated by
      analyzing a certified reference material of water (RTC-QCI-049) with satisfactory
      results. Finally, the proposed method was utilized successfully for the
      determination of copper and mercury in surface water (river), tap water and
      bottled mineral water samples.

PMID- 22983202
TI  - The optical properties, synthesis and characterization of novel 5-aryl-3
      benzimidazolyl-1-phenyl-pyrazoline derivatives.
AB  - A series of novel 5-aryl-3-benzimidazolyl-1-phenyl-pyrazoline derivatives were
      synthesized by the reaction of benzimidazolyl chalcone and phenylhydrazine in 41
      72% yields. The compounds were characterized using IR, (1)H NMR and HRMS.
      Absorption and fluorescence spectra were measured in different organic solvent.
      An intense absorption maxima was noted at ca. 370 nm and emission maxima was
      noted at ca. 460 nm. The absorption spectra of the pyrazoline derivatives reveal
      that 5-aryl group attached to the pyrazoline ring hardly influenced the maximum
      absorption. The fluorescence spectra of these compounds indicated the emission
      wavelength was red shifted and the fluorescence intensity was decreased with the
      increase in solvent polarity.

PMID- 22983203
TI  - Efficient phyto-synthesis and structural characterization of rutile TiO2
      nanoparticles using Annona squamosa peel extract.
AB  - In the present study, the biosynthesis of rutile TiO(2) nanoparticles (TiO(2)
      NPs) was achieved by a novel, biodegradable and convenient procedure using fruit
      peel Annona squamosa aqueous extract. This is the first report on the new,
      simple, rapid, eco-friendly and cheaper methods for the synthesis of rutile
      TiO(2) NPs at lower temperature using agricultural waste. Rutile TiO(2) NPs were
      characterized by UV, XRD, SEM, TEM and EDS studies. The UV-Vis spectrophotometer
      results were promising and showed a rapid production of TiO(2) NPs with a surface
      plasmon resonance occurring at 284 nm. The formation of the TiO(2) NPs as
      observed from the XRD spectrum is confirmed to be TiO(2) particles in the rutile
      form as evidenced by the peaks at 2theta=27.42 degrees , 36.10 degrees , 41.30
      degrees  and 54.33 degrees  when compared with the literature. The TEM images
      showed polydisperse nanoparticles with spherical shapes and size 23+/-2 nm
      ranges.

PMID- 22983204
TI  - Vibrational spectroscopic, molecular structure, first hyperpolarizability and NBO
      studies of 4'-methylbiphenyl-2-carbonitrile.
AB  - The FT-IR, FT-Raman spectra and XRD of 4'-methylbiphenyl-2-carbonitrile were
      recorded and analyzed. The frequencies were computed at various density
      functional theoretical levels using Gaussian09 software package. The data
      obtained from theoretical calculations were used to assign vibrational bands
      obtained in infrared and Raman spectra of the studied molecule. Potential energy
      distribution of the normal modes of vibrations were done using GAR2PED program.
      The geometrical parameters of the title compound are in agreement with XRD
      crystal structure data. The first hyperpolarizability is comparable with the
      reported values of similar derivatives and is an attractive object for future
      studies of non linear optics. The stability of the molecule arising from hyper
      conjugative interaction and charge delocalization has been analyzed using NBO
      analysis. According to XRD data, the dihedral angles between the mean planes of
      the two benzene rings is 44.7 degrees  and the crystal packing is stabilized by
      weak intermolecular pi-pi stacking interactions.

PMID- 22983205
TI  - Spectroscopic investigations of Fe3+ doped poly vinyl alcohol (PVA) capped ZnSe
      nanoparticles.
AB  - Fe(3+) doped poly vinyl alcohol (PVA) capped ZnSe nanoparticles have been
      synthesized by using chemical method at room temperature. The prepared sample is
      characterized by X-ray diffraction, optical, photoluminescence (PL), electron
      paramagnetic resonance (EPR) and FT-IR techniques. Different physical parameters
      are evaluated by using measured values of refractive index and density. From the
      X-ray diffraction pattern, the average crystallite size is calculated by using
      Scherrer's formula and it is about 9 nm. Optical absorption spectrum reveals that
      the Fe(3+) ion enter into the lattice as octahedral symmetry. Crystal field (Dq)
      and inter-electronic repulsion parameters (B, C) are evaluated for Fe(3+) doped
      ZnSe nanoparticles as Dq=720, B=720 and C=2500 cm(-1). Photoluminescence spectrum
      of Fe(3+) doped ZnSe exhibits emission bands in UV and yellow regions. EPR
      spectrum showed various resonance signals at g=7.3, 3.5 and 2.0. FT-IR spectrum
      of Fe(3+) doped PVA capped ZnSe indicates the presence of O-H, C-H, C=C and C=O
      molecular groups.

PMID- 22983206
TI  - Synthetic chloride transporters with the binding mode observed in a ClC chloride
      channel.
AB  - A series of synthetic molecules bearing the same hydrogen bonding mode observed
      in StClC were prepared and their transport ability of chloride ion across a lipid
      membrane was systematically optimized.

PMID- 22983207
TI  - Molecular daisy chains.
AB  - This tutorial review summarizes the progress made towards mechanically
      interlocked daisy chains. Such materials can be seen as a further development in
      polymer science, where the conventional covalent interlinking bonds are replaced
      by supramolecular binding concepts. Materials in which the mechanical bond is an
      integral part of the polymeric backbone are expected to possess unique
      macroscopic properties and are therefore the synthetic aim in an ever growing
      research community. After introducing general considerations about daisy chains,
      the most common analytic methods to get insight into the aggregation behaviour of
      such self-complementary monomers are presented. Cyclodextrins/aromatic rods,
      crown ethers/cationic rods and pillararenes/alkyl chains are systems used to
      achieve daisy chain-like molecular arrays. By comparison of the reported systems,
      conclusions about an improved structural design are drawn.

PMID- 22983208
TI  - Motor circuits are required to encode a sensory model for imitative learning.
AB  - Premotor circuits help generate imitative behaviors and can be activated during
      observation of another animal's behavior, leading to speculation that these
      circuits participate in sensory learning that is important to imitation. Here we
      tested this idea by focally manipulating the brain activity of juvenile zebra
      finches, which learn to sing by memorizing and vocally copying the song of an
      adult tutor. Tutor song-contingent optogenetic or electrical disruption of neural
      activity in the pupil's song premotor nucleus HVC prevented song copying,
      indicating that a premotor structure important to the temporal control of
      birdsong also helps encode the tutor song. In vivo multiphoton imaging and neural
      manipulations delineated a pathway and a candidate synaptic mechanism through
      which tutor song information is encoded by premotor circuits. These findings
      provide evidence that premotor circuits help encode sensory information about the
      behavioral model before shaping and executing imitative behaviors.

PMID- 22983209
TI  - Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling.
AB  - Neurogenesis in the adult hippocampus involves activation of quiescent neural
      stem cells (NSCs) to yield transiently amplifying NSCs, progenitors, and,
      ultimately, neurons that affect learning and memory. This process is tightly
      controlled by microenvironmental cues, although a few endogenous factors are
      known to regulate neuronal differentiation. Astrocytes have been implicated, but
      their role in juxtacrine (that is, cell-cell contact dependent) signaling in NSC
      niches has not been investigated. We found that ephrin-B2 presented from rodent
      hippocampal astrocytes regulated neurogenesis in vivo. Furthermore, clonal
      analysis in NSC fate-mapping studies revealed a previously unknown role for
      ephrin-B2 in instructing neuronal differentiation. In addition, ephrin-B2
      signaling, transduced by EphB4 receptors on NSCs, activated beta-catenin in vitro
      and in vivo independently of Wnt signaling and upregulated proneural
      transcription factors. Ephrin-B2(+) astrocytes therefore promote neuronal
      differentiation of adult NSCs through juxtacrine signaling, findings that advance
      our understanding of adult neurogenesis and may have future regenerative medicine
      implications.

PMID- 22983210
TI  - Path integration: how the head direction signal maintains and corrects spatial
      orientation.
AB  - Head-direction cells have frequently been regarded as an internal 'compass' that
      can be used for navigation, although there is little evidence showing a link
      between their activity and spatial behavior. In a navigational task requiring the
      use of internal cues to return to a home location without vision (path
      integration), we found a robust correlation between head-direction cell activity
      and the rat's heading error in the rat's homing behavior. We observed two
      different correction processes that rats used to improve performance after an
      error. The more frequent one consists of 'resetting' the cell whenever the rat
      returns to the home location. However, we found that when large errors occur, the
      head-direction system has the ability to 'remap' and set a new reference frame,
      which is then used in subsequent trials. We also offer some insight into how
      these two correction processes operate when rats make an error.

PMID- 22983211
TI  - Reversible switching between epigenetic states in honeybee behavioral subcastes.
AB  - In honeybee societies, distinct caste phenotypes are created from the same
      genotype, suggesting a role for epigenetics in deriving these behaviorally
      different phenotypes. We found no differences in DNA methylation between
      irreversible worker and queen castes, but substantial differences between nurses
      and forager subcastes. Reverting foragers back to nurses reestablished
      methylation levels for a majority of genes and provides, to the best of our
      knowledge, the first evidence in any organism of reversible epigenetic changes
      associated with behavior.

PMID- 22983212
TI  - Longitudinal change in bone mineral density in a population-based cohort of
      patients with inflammatory bowel disease.
AB  - Persons with inflammatory bowel disease (IBD) are reported to have a high
      prevalence of osteoporosis and reduced bone mineral density (BMD) and to be at
      higher risk of fracture. The course of BMD loss over time is poorly characterized
      in persons with IBD. Eighty-six persons, stratified by age, were enrolled from a
      population-based longitudinal IBD cohort study to undergo BMD testing at
      baseline, with final BMD testing a mean of 4.3 years later. The proportion of
      subjects with significant change in BMD at the lumbar spine, total hip, and
      femoral neck was assessed, as were clinical, biochemical, and anthropomorphic
      changes. Vertebral radiographs were also obtained at baseline and at the end of
      follow-up in those aged 50 years and above to detect vertebral fractures. The
      change in BMD seen in this cohort of IBD patients was similar to the expected
      rate of BMD loss in the general population. Age >50 years, decreasing body mass
      index (BMI), and corticosteroid use were most notably correlated with BMD loss.
      Subjects aged <50 years did not have statistically significant declines in BMD.
      IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures
      were uncommon, with only two subjects out of 41 >50 years old developing a
      definite radiographic fracture over the course of follow-up. No major
      nonvertebral fractures were observed. Patients with IBD do not appear to have
      significantly accelerated BMD loss. Older age, decreasing BMI, and corticosteroid
      use may identify IBD patients at greater risk for BMD loss.

PMID- 22983213
TI  - Relationship between joint passive stiffness and hip lateral rotator concentric
      torque.
AB  - BACKGROUND: Adequate passive stiffness of the hip joint can prevent the
      occurrence of excessive transverse plane lower limb movement during functional
      activities. Strength training of the hip lateral rotator muscles can be used to
      increase the stiffness of this joint. However, the relationship between hip joint
      passive stiffness and muscle strength remains undocumented in the literature.
      OBJECTIVE: To investigate the association between hip passive stiffness measured
      during medial rotation and hip lateral rotator concentric torque in healthy young
      adults. METHOD: Twenty-six individuals with mean age of 24.42+/-2.77 years
      participated in the present study. To quantify hip stiffness, the passive
      resistance torque during medial rotation was measured using an isokinetic
      dynamometer. Stiffness was determined by the mean slope of the passive torque
      curve obtained in the first 20 degrees  of motion. Electromyography was used to
      ensure inactivity of the hip muscles during this procedure. The isokinetic
      dynamometer was also used for assessment of hip lateral rotator peak torque and
      work in a range of motion of 55 degrees  of rotation. RESULTS: Linear regressions
      demonstrated correlation coefficients of r=0.70 (R2=0.50/p<0.001) and r=0.77
      (R2=0.59/p<0.001) between hip passive stiffness and the measures of lateral
      rotator peak torque and work, respectively. CONCLUSIONS: There is a moderate to
      good association between hip passive stiffness and lateral rotator concentric
      torque. This association suggests that lateral rotator strength training can
      increase hip stiffness.

PMID- 22983214
TI  - Heart rate assessment during maximal static expiratory pressure and Valsalva
      maneuver in healthy young men.
AB  - BACKGROUND: The measure of the maximal expiratory pressure (MEP) has some
      contraindications, as it is believed that the responses obtained in this measure
      are similar to the Valsalva maneuver (VM). OBJECTIVE: The main purpose of this
      study was to evaluate the heart rate responses (HR) during the MEP and the VM
      measures in healthy young men into different postures aiming to identify whether
      and in which situation the MEP reproduces the responses obtained in the VM.
      Additionally we aim to estimate the workload realized during the maneuvers.
      METHOD: Twelve healthy young men were evaluated, instructed and familiarized with
      the maneuvers. The VM was characterized by an expiratory effort (40 mmHg) against
      a manometer for 15 seconds. The MEP measure has been performed according to the
      American Thoracic Society. Both measures were performed at sitting and supine
      positions. ANOVA two-way with Holm-Sidak post-hoc test (p<0.05) was used to
      analyse the heart rate variation (?HR); Valsalva index (VI); MEP index (MEPI),
      and the estimated workload of the maneuvers (Wtotal, Wisotime, Wtotal/?HRtotal
      and Wisotime/?HRisotime ). RESULTS: The ?HR during the maneuvers was not
      influenced by the supine and sitting positions. However, the ?HR during the VM
      and VI were higher (supine: 47+/-9 bpm, 2.3+/-0.2; sitting: 41+/-10 bpm, 2.0+/
      0.2, respectively) than ?HR during the MEP and MEPI values (supine: 23+/-8 bpm,
      1.5+/-0.2; sitting 24+/-8 bpm, 1.6+/-0.3, respectively) (p<0.001). The estimated
      workload of the maneuvers was statistically different (p<0.001) between the
      maneuvers, except to Wtotal/?HR. CONCLUSIONS: In the studied conditions the MEP
      does not reproduces the HR response observed in the VM in healthy young men.

PMID- 22983215
TI  - Association between sarcopenia, sarcopenic obesity, muscle strength and quality
      of life variables in elderly women.
AB  - OBJECTIVE: To investigate the association between sarcopenia, sarcopenic obesity
      and muscle strength and variables related to quality of life in elderly women.
      METHOD: The sample consisted of 56 female volunteers who underwent body
      composition analysis (BMI and x-ray absorptiometry dual-energy DXA). Handgrip
      strength was measured using a Jamar dynamometer. We used the SF-36 health
      questionnaire to analyze quality of life. The data were analyzed with descriptive
      statistics and the Pearson correlation coefficient; SPSS 15.0 was used to perform
      the statistical analysis. RESULTS: The mean age of the subjects was 64.92+/-5.74
      years; of the 56 volunteers evaluated, 19.64% (n=11) were classified as
      sarcopenic obese and 45 (80.36%) were not. Thirteen volunteers (23.21%) were
      classified as sarcopenic while 43 (76.78%) were not. Although there were no
      statistically significant differences between the studied parameters and quality
      of life among those with sarcopenia or sarcopenic obesity, the values were lower
      in affected individuals. Interestingly, handgrip strength correlated positively
      and significantly with all of the SF-36 dimensions except VIT (p=0.08) and SM
      (p=0.25). CONCLUSIONS: Seeing that handgrip strength is a determining factor in
      quality of life aspects in this population, the screening and identification of
      small functional changes using simple clinical measures may facilitate early
      intervention and help prevent disability. In contrast, neither sarcopenia nor
      sarcopenic obesity were found to be associated with quality of life.

PMID- 22983216
TI  - Corticospinal control strategies underlying voluntary and involuntary wrist
      movements.
AB  - The difference between voluntary and involuntary motor actions has been
      recognized since ancient times, but the nature of this difference remains
      unclear. We compared corticospinal influences at wrist positions established
      before and after voluntary motion with those established before and after
      involuntary motion elicited by sudden removal of a load (the unloading reflex).
      To minimize the effect of motoneuronal excitability on the evaluation of
      corticospinal influences, motor potentials from transcranial magnetic stimulation
      of the wrist motor cortex area were evoked during an EMG silent period produced
      by brief muscle shortening. The motoneuronal excitability was thus equalized at
      different wrist positions. Results showed that the unloading reflex was generated
      in the presence of a corticospinal drive, rather than autonomously by the spinal
      cord. Although the tonic EMG levels were substantially different, the
      corticospinal influences remained the same at the pre- and post-unloading wrist
      positions. These influences however changed when subjects voluntarily moved the
      wrist to another position. Previous studies showed that the corticospinal system
      sets the referent position (R) at which neuromuscular posture-stabilizing
      mechanisms begin to act. In self-initiated actions, the corticospinal system
      shifts the R to relay these mechanisms to a new posture, thus converting them
      from mechanisms resisting to those assisting motion. This solves the classical
      posture-movement problem. In contrast, by maintaining the R value constant, the
      corticospinal system relies on these posture-stabilizing mechanisms to allow
      involuntary responses to occur after unloading. Thus, central control strategies
      underlying the two types of motor actions are fundamentally different.

PMID- 22983217
TI  - The effect of apamin, a small conductance calcium activated potassium (SK)
      channel blocker, on a mouse model of neurofibromatosis 1.
AB  - Neurofibromatosis 1 (NF1) is a common genetic disorder known to cause a variety
      of physiological symptoms such as the formation of both benign and malignant
      tumors, and is also known to cause visuospatial learning deficits. Mouse models
      of NF1 show increased GTP activation of ras which may alter K+ channels. One
      candidate K+ channel that may contribute to deficits in NF1 is the SK (small
      conductance calcium-activated potassium) channel due to its role in regulation of
      long term potentiation (LTP), a mechanism of learning which has been shown to be
      impaired in Nf1(+/-) mice. We found that administration of apamin (SK antagonist)
      either through i.p. injection or micro-osmotic pump to Nf1(+/-) mice
      significantly improved performance on the water maze task in comparison to saline
      treated Nf1(+/-) mice on the third day of training and on the corresponding probe
      test. In this study we demonstrate a possible mechanism for the learning deficits
      seen in Nf1(+/-) mice and a possible drug therapy for rescuing these deficits.

PMID- 22983218
TI  - Ancyrocephalidae (Monogenea) of Lake Tanganyika: III: Cichlidogyrus infecting the
      world's biggest cichlid and the non-endemic tribes Haplochromini, Oreochromini
      and Tylochromini (Teleostei, Cichlidae).
AB  - Lake Tanganyika is the deepest and oldest African Great Lake and of economic
      importance. While the diversity of its endemic cichlid radiations yielded
      scientific interest, a number of cichlid tribes have few representatives in the
      lake. Some of those, namely Oreochromini (ex-Tilapiini), Haplochromini and
      Tylochromini, reach higher species numbers in riverine systems. Conversely, the
      phylogenetic position of the monospecific and endemic Boulengerochromini is
      unclear. The oreochromines Oreochromis tanganicae and Oreochromis niloticus, the
      haplochromine Astatotilapia burtoni, the tylochromine Tylochromis polylepis and
      the boulengerochromine Boulengerochromis microlepis, the largest cichlid species
      worldwide, were surveyed for ancyrocephalid monogenean gill parasites. Five new
      species are proposed. Cichlidogyrus gillardinae sp. n. is described from A.
      burtoni, Cichlidogyrus mbirizei sp. n. from O. tanganicae and Cichlidogyrus
      nshomboi sp. n. from B. microlepis. T. polylepis harbours Cichlidogyrus mulimbwai
      sp. n., Cichlidogyrus muzumanii sp. n. and a third, presently undescribed
      species. Four species known from outside the Tanganyika Basin were retrieved on
      the oreochromines. The host species are scientific models or important in the
      sectors of fisheries or ornamental fish trade. Moreover, their phylogenetic
      positions render them well-suited to help elucidate the historic relationships
      between riverine and lacustrine African cichlids. In this framework, their
      Cichlidogyrus fauna is compared to congeners known from African rivers and to the
      few Tanganyika representatives described. While the parasites of Oreochromis, A.
      burtoni and T. polylepis are reminiscent of those infecting related hosts
      throughout Africa, B. microlepis hosts a Cichlidogyrus morphotype typical of Lake
      Tanganyika. This supports its placement within an endemic cichlid radiation.

PMID- 22983219
TI  - Chemical composition and acaricidal activity of essential oil from Lippia
      sidoides on larvae of Dermacentor nitens (Acari: Ixodidae) and larvae and
      engorged females of Rhipicephalus microplus (Acari: Ixodidae).
AB  - The aim of this work was to identify the compounds and to investigate the
      acaricidal activity of the essential oil from the leaves of Lippia sidoides on
      Rhipicephalus microplus and Dermacentor nitens. The oil was obtained by
      hydrodistillation and analyzed by gas chromatography (GC/FID) and gas
      chromatography/mass spectrometry. In total, 15 compounds comprising 99.97 % of
      the total peak area were identified. The main constituent of the essential oil
      was thymol (67.60 %). The acaricidal activity was assessed by the modified larval
      packet test, with oil concentrations of 2.5, 5.0, 10.0, 15.0, and 20.0 MUl/ml,
      and by the female immersion test with concentrations of 10.0, 20.0, 40.0, 60.0,
      and 80.0 MUl/ml. The mortality of the R. microplus and D. nitens larvae was
      greater than 95 % starting at concentrations of 10.0 and 20.0 MUl/ml,
      respectively. In the test with the engorged females, the L. sidoides essential
      oil starting at a concentration of 40.0 MUl/ml caused a significant reduction (p
      < 0.05) in the values of the egg mass weight and egg production index. The
      viability of the eggs was affected in all the treated groups, with significantly
      lower hatching rates (p < 0.05) in relation to the control group. The control
      percentages at concentrations of 10.0, 20.0, and 30.0 MUl/ml were 54, 57, and 72
      %, and reached 100 % at the highest two concentrations (60.0 and 80.0 MUl/ml).
      Therefore, it can be concluded that the essential oil from the leaves of L.
      sidoides has acaricidal activity on R. microplus and D. nitens.

PMID- 22983220
TI  - The sources and metabolic dynamics of Schistosoma japonicum DNA in serum of the
      host.
AB  - The polymerase chain reaction (PCR) assay has turned out to be one of the most
      potential tools for diagnosis of schistosomiasis. However, the source and
      metabolic dynamics of Schistosoma japonicum DNA in the blood of hosts is not
      clear. In this study, rabbit models with monosexual and mixed sexual cercariae
      infection were established to interpret the source of the parasite DNA in serum
      of the hosts. Following administration of praziquantel at 7 weeks postinfection,
      the metabolic mechanism of S. japonicum DNA in serum of the hosts was studied.
      The findings showed that, for the monosexual cercariae infection, the parasite
      DNA was detectable in serum of the host from day 3 to week 3 postinfection, while
      for the mixed sexual cercariae infection, the detection results were continually
      positive during the 7 weeks after infection. After treatment with praziquantel,
      detection of S. japonicum DNA in rabbit sera became positive at the second day
      posttreatment, and the positive period lasted 3 weeks in the monosexual cercariae
      infection group. However, with the mixed sexual cercariae infection group, the
      PCR results remained positive for 16 weeks after treatment. We conclude that the
      S. japonicum DNA in host serum primarily comes from the residual body of dead
      schistosomula and/or tegument shedding of worm growing in the first 4 weeks
      postinfection, while during the spawning stage of the female schistosome, the
      parasite DNA mainly comes from the disintegration of inactive eggs. The duration
      from treatment to total elimination of worm origin DNA in serum is not exceeding
      3 weeks. However, the DNA release from inactive eggs can last for more than 16
      weeks. Further studies are needed to address the sources and metabolic dynamics
      of S. japonicum DNA in human serum.

PMID- 22983221
TI  - Fat graft myringoplasty with the newly developed surgical technique for chronic
      tympanic membrane perforation.
AB  - The purpose of this prospective clinical trial was to evaluate the success rate
      of our newly developed surgical technique for fat graft myringoplasty (FGM). We
      also aimed to assess the correlations between the size of perforations and
      closure rates, as well as the results of re-gained hearing in successful cases
      with respect to sizes of perforations. Thirty consecutive patients with
      persistent tympanic membrane perforation were included in this study. All
      patients underwent fat graft myringoplasty with a newly developed technique.
      Treatment success was defined as an intact tympanic membrane (TM) at the 3-month
      follow-up visit. Bone conduction (BC) and air conduction (AC) thresholds at the
      frequencies of 0.5, 1, 2, 3, and 4 kHz were recorded preoperatively and at the
      3rd month postoperatively. The range of perforation sizes among the 30 patients
      was 7 mm in 13 of the patients (43 %), 6 mm in 8 of the patients (27 %), and 5 mm
      in nine of the patients (30 %). Closure of tympanic membrane perforations with
      this new technique was achieved in 27 out of the 30 patients, with a success rate
      of 90 %. The average of the air-bone gap (dB) was similar in preoperative and
      postoperative periods for 5- and 6-mm sized perforation groups (p = 0.09 and p =
      0.49). However, in the 7-mm sized perforation group, the average of the air-bone
      gap (dB) was higher in the preoperative period than the postoperative period (p =
      0.004). The average of the air-bone gap (dB) for all patients was higher in the
      preoperative period than the postoperative period (p = 0.001). In conclusion, FGM
      performed with this technique may be used as an alternative for the closure of
      tympanic membrane perforations larger than 5 mm.

PMID- 22983222
TI  - Prognostic biological features in neck dissection specimens.
AB  - The superior prognostic value offered by routine histopathological staging of
      neck dissections, as compared to clinical staging using palpation and modern
      imaging techniques, is well established in the literature concerning the
      management of squamous cell carcinoma of the head and neck. In this review, we
      discuss the definitions and criteria used in standardised routine
      histopathological reporting and explore additional potential nodal prognostic
      features. In addition, we critically appraise the value of immunohistochemistry,
      histochemistry, molecular and other non-morphological techniques and suggest
      tumour and host features that merit further investigations.

PMID- 22983225
TI  - [The syndrome of undifferentiated dysplasia of the connective tissue].

PMID- 22983223
TI  - On the genetic control of planar growth during tissue morphogenesis in plants.
AB  - Tissue morphogenesis requires extensive intercellular communication. Plant organs
      are composites of distinct radial cell layers. A typical layer, such as the
      epidermis, is propagated by stereotypic anticlinal cell divisions. It is
      presently unclear what mechanisms coordinate cell divisions relative to the plane
      of a layer, resulting in planar growth and maintenance of the layer structure.
      Failure in the regulation of coordinated growth across a tissue may result in
      spatially restricted abnormal growth and the formation of a tumor-like
      protrusion. Therefore, one way to approach planar growth control is to look for
      genetic mutants that exhibit localized tumor-like outgrowths. Interestingly,
      plants appear to have evolved quite robust genetic mechanisms that govern these
      aspects of tissue morphogenesis. Here we provide a short summary of the current
      knowledge about the genetics of tumor formation in plants and relate it to the
      known control of coordinated cell behavior within a tissue layer. We further
      portray the integuments of Arabidopsis thaliana as an excellent model system to
      study the regulation of planar growth. The value of examining this process in
      integuments was established by the recent identification of the Arabidopsis AGC
      VIII kinase UNICORN as a novel growth suppressor involved in the regulation of
      planar growth and the inhibition of localized ectopic growth in integuments and
      other floral organs. An emerging insight is that misregulation of central
      determinants of adaxial-abaxial tissue polarity can lead to the formation of
      spatially restricted multicellular outgrowths in several tissues. Thus, there may
      exist a link between the mechanisms regulating adaxial-abaxial tissue polarity
      and planar growth in plants.

PMID- 22983227
TI  - [The role of arteriovenous interrelations in the formation of clinical
      pathogenetic variants of hypertonic encephalopathy].
AB  - We studied 209 patients with chronic brain ischemia due to arterial hypertension
      (hypertonic encephalopathy). 93 patients (44.5%) had clinical-anamnestic features
      of constitutional phlebopathy and 116 (55.5%) had not. Based on the conception of
      5 functional-morphological levels of the vascular brain system, a complex
      ultrasound study was conducted. The control group included 30 people without
      cerebrovascular pathology. In hypertonic encephalopathy, pathological processes
      developing in the 1st and 2nd structural-functional levels (extra- and
      intracerebral arteries) correspond to remodeling, that is characteristic of
      arterial hypertension, and do not depend on the presence of the constitutional
      venous insufficiency. Changes in parameters of the blood flow in the 3rd, 4th and
      5th structural-functional levels of the brain's blood supply (microcirculatory
      bed, head venous system, jugular and spine veins) form a dopplerographic pattern
      of the cerebral venous dyscirculation which is mostly pronounced in
      constitutional phlebopathy in patients with hypertonic encephalopathy. This
      pattern includes the reduction of linear blood flow velocity in nitroglycerine
      test, lower values of the resistance index and the increase in the linear blood
      flow velocity in the sinus transversus and Rosenthal vein, lack of ostial valves
      of the inner jugular veinas well as the decrease of linear and increase in the
      volume blood flow velocity along it. The methodology of the system approach based
      on using clinical and instrumental method in the study of cerebral hemodynamics
      is important for treatment optimization in patients with chronic brain ischemia.

PMID- 22983226
TI  - [Focal features of idiopathic generalized epilepsy].
AB  - Idiopathic generalized epilepsies (IGE), in some cases, have focal features in
      the kinematic of seizures and in the EEG. The aim of the paper was to study these
      clinical phenomena using video-EEG monitoring. We studied 180 patients (80 men
      and 100 women) with different forms of IGE with epileptic seizures recorded with
      this method. The effect of the "superposition" of focal electro-clinical features
      on the kinematic matrix and EEG pattern of the generalized myo- (clonic)-tonic
      clonic seizures was noted. The authors suggest to discuss the definition of the
      "phenomenon of secondary focalization". This is the
      clinical/electroencephalographic phenomenon developed in IGE and presented by the
      appearance of secondary focal features (clinical and electroencephalographic) in
      the structure of the generalized epileptic seizure. The evidence for the
      secondary generalization of the seizure with the presence of the regional
      cortical ictogenic source as well as the diagnosis of focal epilepsy are the
      exclusion criteria for the phenomenon of secondary focalization.

PMID- 22983224
TI  - Short- and long-term consequences of nicotine exposure during adolescence for
      prefrontal cortex neuronal network function.
AB  - More than 70% of adolescents report to have smoked a cigarette at least once. At
      the adolescent stage the brain has not completed its maturation. The prefrontal
      cortex (PFC), the brain area responsible for executive functions and attention
      performance, is one of the last brain areas to mature and is still developing
      during adolescence. Smoking during adolescence increases the risk of developing
      psychiatric disorders and cognitive impairment in later life. In addition,
      adolescent smokers suffer from attention deficits, which aggravate with the years
      of smoking. Recent studies in rodents reveal the molecular changes induced by
      adolescent nicotine exposure that alter the functioning of synapses in the PFC
      and that underlie the lasting effects on cognitive function. Here we provide an
      overview of these recent findings.

PMID- 22983228
TI  - [Focal characteristics in the clinical examination and EEG in children with
      idiopathic generalized epilepsy].
AB  - The aim of the study was to determine the prevalence of focal characteristics in
      the clinical symptoms of seizures and in EEG in children with different clinical
      variants of generalized idiopathic epilepsy. We studied 71 patients, 29 boys and
      42 girls, aged from 2 to 18 years. Video-EEG-monitoring and MRI were performed in
      all cases. The results provided further evidence fort the continuum between focal
      and generalized epilepsy supported by the presence of focal characteristics in
      the semiology of seizures and in EEG as well.

PMID- 22983229
TI  - ["Moral mysophobia" phenomenon in schizophrenia].
AB  - Mysophobia - fear of contamination is one of the most prevalent types of the
      obsessive-compulsive disorder (OCD). "Moral mysophobia" is a ritual of
      cleanliness and avoidant behavior due to unpleasant obsessive thoughts. The
      presence of "moral" component in this subtype of contamination fear is supposed
      to cause high level of treatment resistance. The study included 16 patients with
      "moral mysophobia". The psychopathological structure of the phenomenon was
      described. Delusional symptoms and mental automatisms were found to contribute to
      its development. The analysis of schizophrenia course suggested that the
      development of "moral mysophobia" in schizophrenia was based on prominent
      negative symptoms.

PMID- 22983230
TI  - [Effects of mexidol on the functional state of the central nervous system in post
      stroke patients].

PMID- 22983231
TI  - [Atypical absences: prevalence, electroclinical and neuroimaging
      characteristics].
AB  - The study included 1261 patients with different forms of epilepsy. Ages at onset
      of disease varied from the first days of life to 18 years old. Absence seizures
      were identified in 231 (18.3%) patients, atypical absences (AA) in 129 (10.2%) of
      patients, with the frequency of absence seizures 55.8% in the total group.
      Patients with AA had different forms of epilepsy with the prevalence of
      cryptogenic/symptomatic forms with the phenomenon of secondary bilateral
      synchronization in the EEG. If epilepsy manifested itself at the age above 12
      years old, AA were not noted. The study demonstrated the relevance of using video
      EEG monitoring for diagnosis of epilepsy with AA. The antiepileptic treatment was
      effective in 53.5% of patients.

PMID- 22983232
TI  - [The use of reamberini in acute poisonings with psychopharmacological drugs in
      children].

PMID- 22983233
TI  - [Efficasy and safety of the use of risperidone (rispoluxe) in demented patients
      with psychotic and behavioural disorders].
AB  - Based on the comparison of international and Russian studies, authors present a
      review on the epidemiology, clinical features, diagnosis and treatment of
      psychotic and behavioral disorders in patients with dementia. Results of the own
      study on the efficacy of risperidone (rispolux) in dosage 102 mg daily in
      patients with dementia with psychotic and behavioral disorders are presented. It
      has been shown that rispolux reduces psychotic and behavioral disorders, improves
      cognitive functions. It is well-tolerated and rather safe for elderly patients.

PMID- 22983234
TI  - [The course and treatment of epilepsy in children with tuberose sclerosis].
AB  - Tuberous sclerosis complex is a multisystem genetic disorder. Epilepsy is very
      common in tuberous sclerosis and occurs in 75-92% of affected individuals during
      their life-time. Onset usually occurs during childhood and up to one third of
      children with tuberous sclerosis will develop infantile spasms. Of all the
      possible manifestations of this complex disorder the resistant epilepsy, the
      cognitive and behavioral problems represent the area of greatest concern to
      parents, caregivers and physicians. Treatment of epilepsy in tuberous sclerosis
      is similar to epilepsy resulting from other cases and includes anticonvulsant
      medications, the epilepsy surgery, the vagus nerve stimulation and the ketogenic
      diet. Vigabatrin has been shown to be particularly effective in treating
      infantile spasms in the setting of tuberous sclerosis.

PMID- 22983235
TI  - [Branded drugs and generics: an ambiguity of choice].
AB  - In Russia, the problem of choice between branded drugs and generics is extremely
      urgent because funding should be spent efficiently in conditions of strict
      financial restrictions. However the seeming economy in using generics which are
      not therapeutically equivalent to branded drugs leads to the decrease of clinical
      of treatment effectiveness and to the increase of treatment costs as well. The
      authors analyze the problem in respect to the Russian pharmaceutical market. It
      is concluded that the choice of the generic is reasonable if there is evidence
      for its therapeutic equivalence with the branded drugs. To improve the quality of
      medical care, one should pay special attention to the quality of generics in the
      market.

PMID- 22983236
TI  - [Efficacy of the specific prolonged form of valproic acid (in the form of
      granules) in children with different forms of epilepsy].

PMID- 22983237
TI  - [Ischemic cochlear vestibular syndromes].

PMID- 22983238
TI  - [Complex therapy of idiopathic forms of epilepsy with small doses of valproates
      and levetiracetam].
AB  - A combination of valproates in dose 15-25 mg per day and levetiracetam in dose 20
      25 mg per day was used in the treatment of 23 patients with different forms of
      epilepsy (juvenile myoclonic epilepsy, juvenile absence epilepsy, convulsive
      idiopathic generalized epilepsy and children absence epilepsy). The use of these
      drugs was effective in all forms of epilepsy. There were positive changes in the
      frequency of seizures and epileptic activity in the EEG.

PMID- 22983239
TI  - [The assessment of prognosis of carotid endarterectomy by clinisal-mathematical
      method].
AB  - We examined 127 patients with atherosclerotic stenosis of carotid arteries who
      underwent carotid endarterectomy (CEAE). In the most of patients (85%), CEAE
      slowed the progression of chronic cerebral ischemia leading to the stabilization
      or improvement of neurologic and/or neuropsychological status. The analysis of
      the data allowed to suggest a mathematical model for predicting the outcome of
      the surgery.

PMID- 22983240
TI  - [The results of the use of levetiracetam (keppra) in post-stroke epilepsy].

PMID- 22983241
TI  - [A complex study of the movement biomechanics in patients with post-stroke
      hemiparesis].
AB  - The authors present results of a pilot study on biomechanics of non-cyclic
      movements of the human consequent verticalization in the ontogenesis of patients
      with post-stroke hemiparesis (10 patients in the acute stage of cerebral stroke)
      and 10 healthy volunteers without neurologic and orthopedic pathology. Some
      movements of therapeutic exercises Balance (a model of ontogenetic kinesitherapy)
      have been selected for the study. Cinematic parameters have been recorded using a
      system of motion 3D video analysis, a kinematic model was build in accordance to
      standard protocols. The skin (native and straightened) electromyogram (EMG) was
      recorded synchronously with kinematic data using 16-channel electromyography from
      the following pairs of muscles: mm. sternocleido-mastoideus, trapezius
      (gorizeontal?naya portsiya), biceps brachii, triceps brachii, rectus femoris,
      adductor magnus. Major differences in the EMG picture between patients and
      controls were: 1) the EMG "monotony" with the involvement of multiple additional
      muscles in locomotions with the prevalence of the peculiar "tonic" muscle
      activity (low amplitudes without distinct peaks), stretching along the whole
      cycle of movement. In controls, EMG demonstrated variability and had mostly
      "phasic" character with distinct 1 or 2 peaks; 2) the asymmetry of EMG profile in
      symmetric movements. i.e. when performed simultaneously from the right and from
      the left sides. The latter feature may be considered as predictive because it was
      never found in healthy people. It allows to identify objectively weak muscles
      even in the absence of visible parethis during the routine neurological
      examination.

PMID- 22983242
TI  - [Idiopathic generalized epilepsy in young women: choise of treatment strategy].
AB  - We studied 279 women, aged 18-40 years old, with epilepsy. The study included the
      evaluation of anamnesis, clinical and neurological examination, routine EEG
      and/or video-EEG-monitoring, MRI of the brain. The period of observation was 6
      months - 8 years. Idiopathic generalized epilepsy (IGE) was diagnosed in 85
      cases, cryptogenic focal epilepsy in 107 cases, symptomatic focal epilepsy in 51
      cases, unclassified epilepsy in 32 cases. In the end of study, remission was
      achieved in 70.8% of patients of the IGE group, the substantial reduction in the
      number of seizures was identified in 13.8%, no effect was seen in 15.4%. Adverse
      events were found in 22 of 63 (34.9%) patients treated with valproates, 9 of 25
      (36%) patients treated with topiramate, 5 of 39 (1.8%) patients treated with
      carbamazepine, 3 of 7 (42.9%) patients treated with levetiracetam and in 2 of 5
      (40%) patients treated with lamotrigine. The aggravation of absences with
      carbamazepine was diagnosed in 2 cases, myoclonic seizures - in 2 cases.
      Therapeutic strategies of young women with juvenile forms of IGE were described
      and analyzed.

PMID- 22983243
TI  - [The role of sex hormones in the development of affective disorders in women with
      epilepsy].
AB  - The objective of this study was the comprehensive assessment of the association
      between the level of hormones, reproductive disorders, symptoms of epilepsy and
      psychopathological symptoms in female patients with epilepsy and affective
      disorders. We studied 101 women using clinical and psychopathological
      examination, hormone measurement and statistical analysis. The data analysis
      showed correlations between scores on the scales measuring the mental health
      status and the level of hormones in the blood of patients. It has been concluded
      that the effect of female sex hormones on affective symptoms depends on
      characteristics of depressive affect.

PMID- 22983244
TI  - [Amino acids content in the blood serum of patients with multiple sclerosis].
AB  - Content of amino acids in the blood serum using ion-exchange chromatography and a
      quantitative crystalloscopic "closed drop" method was measured in 105 patients
      with multiple sclerosis of different severity. The relation between the dynamics
      of content of glutamic, asparagine acids and glycine and the disease severity was
      determined. The highest level of glutamic acid was found in the patients with
      severe disease course. The dynamics of quantitative changes in the amino acid
      content was accompanied by the disturbance of blood serum structuration and
      appearance of selective micromorphotypes. The positive correlation between the
      severity of motor and coordination disorders and the increase in levels of
      glutamic acid and glycine in the severe cases was detected.

PMID- 22983245
TI  - [Clinical-genetic analysis of limb-girdle muscular dystrophy 2 type I].
AB  - Seventy four patients with clinical presentation of LGMD and probably autosomal
      recessive type of inheritance were examined. Five different mutations of FKRP
      gene responsible for LGMD2 type I were detected in eight (10.8%) patients. Two of
      them s.341C>G, c.826C>A were described before and three c.229C>T, s.265C>T,
      s.1078G>C were found for the first time. The significant clinical polymorphism
      due to the difference in age of manifestation and severity of clinical
      presentation was identified.

PMID- 22983246
TI  - [Pharmacotherapy of epilepsy: the use of topiramate in initial and additional
      treatment].
AB  - Topiramate (topamax) is an antiepileptic drug of the new generation that was
      first registered and introduced in clinical practice in 1995. Due to its
      effective clinical properties, the drug is used widely all over the world
      including Russia where it has been using since 1999. Topamax is a principally new
      antiepileptic drug (AED) with the unique mechanism of action, favorable
      pharmacokinetics, high efficacy and safety. During its existence, it is widely
      accepted as an AED of first choice for additional and initial treatment of many
      forms of epilepsy in children over 2 years old and adults including old patients
      of both sexes. The drug can be successfully used as monotherapy and as well as
      polytherapy in treatment of most severe and "catastrophic" epilepsies resistant
      to any previous treatment.

PMID- 22983247
TI  - [The models for some indicators of assessment of Russian health services
      performance].

PMID- 22983248
TI  - [Focal cortical atrophies].

PMID- 22983249
TI  - [Lacosamide in the treatment of epilepsy].
AB  - The new antiepileptic drug (AED) lacosamide (vimpat, "UCB Pharma") with a new
      mechanism of action was registered in Russia in 2010. The drug should be used as
      add-on treatment in patients over 16 years and older with non-controlled focal
      seizures with- or without secondary localization. The authors review the data of
      literature and the results of trials on efficacy and safety of lacosamide for
      peroral and intravenous introduction. Randomized clinical trials of the peroral
      form of this drug provide evidence that lacosamide is a prospective preparation
      for complex treatment of drug-resistant epilepsy in the view of its safety and
      tolerability. The availability of the infusion form is advantageous compared to
      other AED making it possible to continue treatment in cases when the peroral
      intake of AED is temporary impossible.

PMID- 22983250
TI  - [Autonomic, anxiety-depressive disorders and quality of life in women kept in
      penitentiary institutions].

PMID- 22983251
TI  - [Chronic disorders of brain blood circulation and possibilities of their
      pharmacological correction].

PMID- 22983252
TI  - [Pathology of collagen and cerebrovascular disorders].

PMID- 22983253
TI  - [Age aspects of quality of life research in patients with epilepsy].
AB  - In spite of the fact that patients of advanced age are the fastest growing
      population of patients with epilepsy, there is no sufficient data on quality of
      life (QOL) questionnaires sensitivity in the elderly patients. The aim of this
      study was to evaluate correlations between QOLIE-31 and QOLIE-10 scores in the
      elderly and young patients with epilepsy before and after antiepileptic therapy
      optimization. Twenty-seven elderly (average age 65.36+/-3.88 years) and 30 young
      (average age 25.05+/-3.06 years) patients completed questionnaires QOLIE-31 and
      QOLIE-10 The analysis of QOL indicators was conducted at the following control
      points: 1) before the beginning or correction of antiepileptic therapy; 2) 6
      months after the beginning of therapy or its optimization. In young patients
      after the beginning or optimization of therapy, the statistically significant
      negative correlation between the majority QOLIE-31 subscales and a total QOLIE-10
      score, with the exception of the "Emotional well-being", was revealed. In the
      elderly patients, the positive correlations with the "Energy/fatigue" (r=0.46)
      and the "Medications effect" (r=0.20) subscales were noted. Considering the score
      estimation in QOLIE-31 and QOLIE-10 questionnaires, the revealed positive
      correlations could testify smaller sensitivity of questions in the brief version
      (QOLIE-10) in the elderly patients with epilepsy in comparison with young
      patients. According to the data received, the validity of QOLIE-10 appeared to be
      insufficient in the elderly patients, with the QOLIE-31 questionnaire being
      preferred. In young patients, the QOLIE-10 can be recommended as a screening QOL
      tool at the beginning of antiepileptic therapy, and later for estimation of AEDs
      efficiency.

PMID- 22983254
TI  - [Nonmotor symtoms in Parkinson disease].

PMID- 22983255
TI  - [Neurovisualization in the differential diagnosis of dementia].

PMID- 22983256
TI  - [Possibilities in using sulpiride in the treatment of psychotic disorders].

PMID- 22983257
TI  - [The results of the clinical and epidemiological study of epilepsy in urban and
      rural areas of the Dagestan Republic].
AB  - The results of the clinical and epidemiological study of epilepsy in the Soviet
      region of Makhachkala city and the Khasavurt region of the Dagestan Republic are
      presented. The sample size was 139.115 in the Soviet region and 101.278 in the
      Khasavurt region, The samples included 344 and 338 patients with epilepsy,
      respectively. The age- and sex- standardized prevalence of epilepsy was 2.06
      (CI95% 1.80-2.32) cases per 1000 population in the Soviet region and 2.98 (CI95%
      2.60-3.35) cases per 1000 population in the Khasavurt region (p=0.05). The
      prevalence of epilepsy was higher in men. Focal (location-related) forms of
      epilepsy were most frequent, with the highest frequency of partial seizures with
      secondary generalization. Cranial-brain injury, intra- and perinatal pathology
      and cerebral vascular diseases were the main causes of the development of focal
      epilepsies. Seizure frequency greater than 12 per year was noted in more than a
      half of patients. The study of social aspects showed that only small portion of
      patients worked, most of patients received disability pensions. Differences in
      the education level were identified as well.

PMID- 22983258
TI  - Cardiovascular magnetic resonance imaging and transthoracic echocardiography in
      the assessment of stenotic aortic valve area: a comparative study.
AB  - BACKGROUND: Magnetic resonance (MR) imaging and echocardiography both allow
      assessment of aortic valve stenosis. In MR the aortic valve area (AvA) is
      measured using planimetry while in transthoracic echocardiography (TTE) AvA is
      usually calculated by applying the continuity equation. PURPOSE: To compare the
      measured stenotic aortic valve areas using five different MR-acquisition
      alternatives with the corresponding area values calculated by TTE. MATERIAL AND
      METHODS: The aortic valve was imaged in 14 patients, with diagnosed aortic valve
      stenosis, using balanced steady state free precession (bSSFP) gradient echo (GE)
      and phase contrast imaging (PC). Three adjacent slices were planned to encompass
      the aortic valve and the aortic valve area was measured using planimetry. The two
      sets of complex valued images generated by the PC sequence formed three kinds of
      images that could be used for aortic valve area measurements: the magnitude image
      (PC/Mag), the modulus (PCA/M), and phase difference (PCA/P) between the two
      complex images, respectively. The valve area from TTE was calculated using the
      continuity equation. A cut-off of <1.0 cm(2) was used as a criteria for severe
      stenosis. RESULTS: The mean area differences between the different MR
      acquisitions and TTE method were -0.05 +/- 0.37 cm(2) (GE), -0.18 +/- 0.46 cm(2)
      (bSSFP), 0.27 +/- 0.43 cm(2) (PC/Mag), 0.15 +/- 0.32 cm(2) (PCA/P), and 0.26 +/-
      0.27 cm(2) (PCA/M). The valve area was significantly overestimated using PCA/M
      that, in turn, implied a significant underestimation of the aortic valve stenosis
      severity compared to the assessments using TTE. CONCLUSION: The smallest area
      valve difference between TTE and an MR-acquisition alternative is obtained with
      gradient echo images. The use of PCA/M leads to significant differences in
      planimetry measurements of the aortic valve orifice and the gradation of the
      stenosis severity compared to TTE.

PMID- 22983259
TI  - An observational study to evaluate the efficiency and safety of ioversol pre
      filled syringes compared with ioversol bottles in contrast-enhanced examinations.
AB  - BACKGROUND: The use of pre-filled syringes for contrast media (CM) administration
      allows efficient and optimized workflow during radiologic diagnostic procedures,
      and reduces the risk of contamination, providing benefits for both patients and
      healthcare workers. PURPOSE: To compare the efficiency and safety of ioversol
      (Optiray(TM)) bottles and pre-filled syringes in clinical practice. MATERIAL AND
      METHODS: This was an observational, non-interventional, prospective, multicenter
      study conducted at 72 centers in Germany. Patients undergoing contrast-enhanced
      computed tomography (CT) examinations with ioversol were enrolled. The use of
      ioversol bottles and pre-filled syringes in the diagnostic procedure was recorded
      in terms of efficiency (residual volume, re-use of CM) and safety (adverse events
      [AEs]). RESULTS: A total of 10,836 patients were enrolled and included in this
      study. Ioversol bottles and syringes were used in 72% and 28% of cases,
      respectively. Analysis of the volume of CM in bottles before and after
      examinations, together with the volume used during the examination, suggested
      that in 22.5% of cases a new bottle was connected during the procedure. Further
      analysis revealed that in 80.2% of cases, the remaining volume of CM in the
      bottles could potentially be used for subsequent investigations, compared with
      <1% of cases for pre-filled syringes. For the total study population, AEs and
      serious AEs were reported in 30 (0.28%) and four (0.037%) patients, respectively,
      with no significant difference observed between ioversol bottles and syringes.
      CONCLUSION: Administration of ioversol for contrast-enhanced CT examinations is
      associated with a low incidence of AEs and is generally safe and well tolerated.
      Ioversol pre-filled syringes were associated with lower residual volumes and less
      potential re-use compared with bottles.

PMID- 22983260
TI  - Characteristic CT and MRI findings of intracranial chondroma.
AB  - BACKGROUND: Intracranial chondromas are rare benign tumors. To date, few data are
      available on their neuroradiological features. PURPOSE: To describe a series of
      patients with intracranial chondroma and to analyze and discuss the computed
      tomography (CT) and magnetic resonance imaging (MRI) features that may
      distinguish chondromas from other intracranial neoplasms. MATERIAL AND METHODS:
      We retrospectively analyzed clinical and medical imaging data of six patients who
      had pathologically confirmed intracranial chondromas in our two institutions
      between July 2006 and September 2011. Both CT and MRI scanning were performed in
      all six cases. RESULTS: Five tumors were located at the skull base and one
      originated from the falx. CT images revealed well-demarcated, irregular lobulated
      and variable density masses with obvious calcification (6/6), no or slight
      enhancement, without peritumoral edema, and frequently accompanied by erosion and
      destruction of surrounding bone (5/6). Tumor parenchyma appeared heterogeneously
      hypointense on T1WI, and hyperintense or mixed hyperintense and hypointense on
      T2WI, while the calcification appeared hypointense on T1WI and T2WI in five
      cases, demonstrating significant inhomogeneous enhancement on postcontrast MRI,
      which revealed the typical "punica granatum seeds" sign. Only one case showed
      homogeneous low signal intensity on T1WI and high signal intensity on T2WI, and
      relatively uniform obvious enhancement on postcontrast scans. CONCLUSION: These
      characteristic CT and MR findings, combined with the location of the lesions and
      the history of a long duration of clinical symptoms, may prove helpful in
      differentiating intracranial chondromas from other more common tumors.

PMID- 22983261
TI  - RNA2DMap: A Visual Exploration Tool of the Information in RNA's Higher-Order
      Structure.
AB  - A new and emerging paradigm in molecular biology is revealing that RNA is
      implicated in nearly every aspect of the metabolism in the cell. To enhance our
      understanding of the function of these RNA molecules in the cell, it is essential
      that we have a complete understanding of their higher-order structures. While
      many computational tools have been developed to predict and analyse these higher
      order RNA structures, few are able to visualize them for analytical purposes. In
      this paper, we present an interactive visualization tool of the secondary
      structure of RNA, named RNA2DMap. This program enables multiple-dimensions of
      information about RNA structure to be selected, customized and displayed to
      visually identify patterns and relationships. RNA2DMap facilitates the
      comparative analysis and understanding of RNAs that cannot be readily obtained
      with other graphical or text output from computer programs. Three use cases are
      presented to illustrate how RNA2DMap aids structural analysis.

PMID- 22983263
TI  - An efficient labeling strategy of drug like molecules with functionalized alkyl
      linkers using CH-activation.
AB  - Heterocyclic drugs can be cross-coupled with functionalized thiophene derivatives
      under dehydrogenative conditions using Pd-catalysts. Upon reductive
      desulfurization an alkyl linker is introduced with a functional group at its
      terminus, which will allow the immobilization of the drug molecule onto a solid
      support for chemical proteomics.

PMID- 22983262
TI  - Novel target genes and a valid biomarker panel identified for cholangiocarcinoma.
AB  - Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate
      is high due to late clinical presentation. CpG island promoter methylation is
      frequently seen in cancer development. In the present study, we aimed at
      identifying novel epigenetic biomarkers with the potential to improve the
      diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of
      cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated
      counterparts were compared with previously published gene expression profiles of
      primary tumors and with non-malignant controls. Genes responding to the
      epigenetic treatment that were simultaneously downregulated in primary
      cholangiocarcinoma compared with controls (n = 43) were investigated for their
      promoter methylation status in cancer cell lines from the gastrointestinal tract.
      Genes commonly methylated in cholangiocarcinoma cell lines were subjected to
      quantitative methylation-specific polymerase chain reaction in a total of 93
      clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1,
      SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and
      were unmethylated in controls. At least one of these four biomarkers was positive
      in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel
      methylation-based biomarker panel showed high sensitivity and specificity for
      cholangiocarcinoma. The potential of these markers in early diagnosis of this
      cancer type should be further explored.

PMID- 22983265
TI  - Relationship between self-reported high-heeled shoe use and bone mineral density
      using quantitative ultrasound at a community health fair.
AB  - This is the first known study to examine the relationship between high-heel use
      and bone mineral density (BMD). Because women are disproportionately affected by
      osteoporosis, it is important to identify possible modifiable behaviors of women
      that may adversely affect bone health. Many studies have shown changes in body
      mechanics when wearing high-heeled shoes in comparison to normal gait. Because
      the composition of bone changes according to mechanical load and muscle activity,
      this study investigates whether wearing high heels may alter BMD. Two hundred and
      twenty-one participants at a community health fair in Lansing, Michigan, were
      surveyed on high-heel use and bone health risk (gender, thin/small frame, fair
      skin, family history of fracture, smoking history, walking, dairy consumption,
      and early menopause or oopherectomy at <45 years old). Quantitative ultrasound
      (QUS) of the heel by Hologic's Sahara Sonometer was used to measure BMD. The mean
      age was 45.2 (SD 13.7) years, and the majority of participants were female (208,
      94 %). A significant difference between mean BMD and high-heel use was not found.
      Independent correlations existed between fair skinned/sunburn easily and BMD,
      r(212) = -0.14, p = 0.038, as well as history of smoking and BMD, r(212) = -0.14,
      p = 0.042. Bone health risk score was strongly correlated with heel use binary
      variable "yes/no," r(210) = 0.21, p = 0.003. Our study suggests that wearing high
      heeled shoes does not lead to appreciable differences in BMD among community
      health fair participants as assessed by QUS.

PMID- 22983264
TI  - Dysfunctional pain inhibition in patients with chronic whiplash-associated
      disorders: an experimental study.
AB  - Inefficient endogenous pain inhibition, in particular impaired conditioned pain
      modulation (CPM), may disturb central pain processing in patients with chronic
      whiplash-associated disorders (WAD). Previous studies revealed that abnormal
      central pain processing is responsible for a wide range of symptoms in patients
      with chronic WAD. Hence, the present study aimed at examining the functioning of
      descending pain inhibitory pathways, and in particular CPM, in patients with
      chronic WAD. Thirty-five patients with chronic WAD and 31 healthy controls were
      subjected to an experiment evaluating CPM. CPM was induced by an inflated
      occlusion cuff and evaluated by comparing temporal summation (TS) of pressure
      pain prior to and during cuff inflation. Temporal summation was provoked by means
      of 10 consecutive pressure pulses at upper and lower limb location. Pain
      intensity of first, fifth, and 10th pressure pulse was rated. During heterotopic
      noxious conditioning stimulation, TS of pressure pain was significantly depleted
      among healthy controls. In contrast, TS was quite similar prior to and during
      cuff inflation in chronic WAD, providing evidence for dysfunctional CPM in
      patients with chronic WAD. The present study demonstrates a lack of endogenous
      pain inhibitory pathways, and in particularly CPM, in patients with chronic WAD,
      and hence provides additional evidence for the presence of central sensitization
      in chronic WAD.

PMID- 22983267
TI  - The value of criterion-based surgical education.

PMID- 22983266
TI  - Increased circulating fibrinogen-like protein 2 in patients with systemic
      sclerosis.
AB  - Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen-related superfamily
      of proteins, is expressed on the surface of macrophages, T cells, and endothelial
      cells and directly cleaves prothrombin to thrombin. The aim of this study is to
      determine the serum FGL2 level and its association with clinical parameters in
      patients with systemic sclerosis (SSc). Serum FGL2 level was examined by enzyme
      linked immunosorbent assay in 61 patients with SSc, 24 patients with systemic
      lupus erythematosus, and 24 healthy individuals. In a retrospective longitudinal
      study, sera from 13 patients with SSc were analyzed. The serum FGL2 level was
      increased in patients with SSc compared with healthy individuals (P < 0.001) and
      patients with systemic lupus erythematosus (P < 0.01). Among patients with SSc,
      there were no differences in serum FGL2 level between limited cutaneous SSc and
      diffuse cutaneous SSc. In the longitudinal study, the FGL2 level was generally
      unchanged at follow-up. The results show that the serum FGL2 level was increased
      in patients with SSc but not in patients with systemic lupus erythematosus or
      healthy individuals. Therefore, FGL2 possibly contribute to the development of
      SSc.

PMID- 22983268
TI  - Urogynecological causes of pain and the effect of pain on sexual function in
      women.
AB  - Female Sexual Dysfunction (FSD) is a complex biopsychosocial phenomenon.
      Screening, identifying and managing urogenital and sexual symptoms often result
      in significant improvement in women's quality of life. Providers must proactively
      question patients about possible presence of FSD. When a sexual problem is
      present, identify the type of FSD, counsel patients on the appropriate approaches
      to treatment. No single therapeutic approach is effective in treating all types
      of FSD.

PMID- 22983269
TI  - Improving resident competence and knowledge regarding tension-free vaginal tape
      procedure:  an educational module.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of a
      teaching module using simulation for the tension-free vaginal tape (TVT)
      procedure on procedural knowledge and skill. METHODS: Twenty-five gynecology
      residents participated in a teaching module about the TVT procedure and urinary
      incontinence, which included a simulated insertion on a training model.
      Questionnaires using 10-point scales for self-rated competence and knowledge and
      a written examination were administered before and after the module. A simulated
      TVT insertion was evaluated at an examination at 7 weeks and at 7 months.
      RESULTS: A significant median improvement of 44% on the written examination and
      at least one point on each of the self-rated competence and knowledge scales were
      observed after the teaching module. Residents performed the insertion well at
      both examinations (89% and 90%), regardless of surgical experience. More than 94%
      agreed the module was useful and improved their understanding of the procedure.
      CONCLUSION: A short teaching module and simulation session can effectively teach
      residents and improve their perceived competence with the TVT procedure.

PMID- 22983270
TI  - Major postoperative complications after benign gynecologic surgery:  a clinical
      prediction tool.
AB  - OBJECTIVE: The objective of this study was to create a clinical prediction tool
      to differentiate women at risk for postoperative complications after benign
      gynecologic surgery. METHODS: We utilized the 2005 to 2009 American College of
      Surgeons National Surgical Quality Improvement Program participant use data files
      to perform a secondary data-set analysis of women older than 16 years who
      underwent benign gynecologic procedures. We then temporally divided women into 2
      similar cohorts. Our derivation cohort included all women undergoing benign
      gynecologic procedures in 2005 to 2008. Our validation cohort included all women
      undergoing benign gynecologic procedures in 2009. The primary outcome, composite
      30-day major postoperative complications, was analyzed as a dichotomous variable.
      A prediction tool was then constructed to predict the occurrence of postoperative
      complications built from the logistic regression model by rounding the value of
      each estimated beta coefficient to the nearest integer. An individual's risk
      score was then computed by summing the number of points based on her preoperative
      characteristics. This risk score was then used to categorize women into low-,
      medium-, and high-risk groups. RESULTS: A prediction tool for benign gynecologic
      procedures identified women at low (2.7% and 2.4%), medium (6.3% and 6.8%), and
      high (29.5% and 23.8%) risk of complications in the derivation and validation
      cohorts, respectively. CONCLUSIONS: A prediction tool can differentiate women at
      risk for postoperative complications after benign gynecologic surgery.

PMID- 22983271
TI  - Surgeon practice patterns for antibiotic prophylaxis in gynecologic surgery.
AB  - OBJECTIVE: To assess surgeon practice patterns for antibiotic prophylaxis in
      gynecologic surgery. METHODS: A survey was distributed at the 2011 annual
      scientific meeting of the Society of Gynecologic Surgeons regarding antibiotic
      prophylaxis practices. RESULTS: The response rate was 51%. Most surgeons did not
      use antibiotic prophylaxis for dilation and curettage without products of
      conception, hysteroscopy, and loop electrocautery excision procedure/cone biopsy.
      For laparoscopy without graft placement, 45.9% did not use prophylaxis.
      Prophylaxis was common for hysterectomy. For midurethral slings, 8.2% did not use
      prophylaxis. When graft material was used in prolapse surgery, at least 93% of
      surgeons administered some form of antibiotic prophylaxis. Only 70% of
      respondents prescribe antibiotic prophylaxis for hysterectomy consistent with
      recommendations from the American College of Obstetricians and Gynecologists,
      whereas 78% are consistent with specifications from the Joint Commission.
      CONCLUSIONS: Wide variability exists in antibiotic prophylaxis in gynecologic
      surgery. Surgeon preference or local hospital policies affect choice of
      prophylaxis less than 14.9% of the time.

PMID- 22983272
TI  - Abdominal sacral hysteropexy:  a pilot study comparing sacral hysteropexy to
      sacral colpopexy with hysterectomy.
AB  - OBJECTIVES: Treatment of pelvic prolapse with uterine conservation using the
      sacral hysteropexy may be associated with less patient morbidity but has
      uncertain subjective and objective outcomes. We sought to compare abdominal
      sacral hysteropexy (ASH) with sacral colpopexy/total abdominal hysterectomy
      (ASC/TAH). METHODS: This is an ambispective (retrospective/prospective) cohort
      pilot study comparing ASH to ASC/TAH. The primary outcome was global impression
      of improvement. Secondary outcomes were based on validated quality-of-life
      questionnaires and surgical complications. RESULTS: Eighteen ASHs were compared
      to 9 ASC/TAHs after a mean follow-up of 19 months. Whereas subjective outcomes
      did not differ, anterior failure (55%) and subsequent uterine pathology (22%)
      were higher in the ASH cohort. Graft erosion occurred in 33% of the ASC/TAH
      group. CONCLUSIONS: The ASH offers advantages and disadvantages that warrant
      further investigation with a prospective study.

PMID- 22983274
TI  - Long-term self-assessment of urinary continence after stress urinary incontinence
      surgery.
AB  - OBJECTIVES: To evaluate the long-term subjective urinary continence status and
      quality of life after 3 types of primary operation for stress urinary
      incontinence. METHODS: One hundred thirty-four consecutive patients who underwent
      anti-incontinence surgery (laparoscopic colposuspension, classic tension-free
      vaginal tape procedure, or open colposuspension) 6 to 9 years ago were mailed
      short-form questionnaires of the International Consultation on Incontinence
      Questionnaire-Urinary Incontinence. For statistical analysis, the Student t test,
      the chi test, and the analysis-of-variance test were used. RESULTS: Eighty-seven
      patients (64.9%) returned the questionnaire. The mean follow-up was 7.48 years
      (range, 6-9 years). Patients in the tension-free vaginal tape group were
      significantly older (P < 0.001). After primary operation, 7.4% (2 of the 27
      patients) in the laparoscopic colposuspension group, 23.53% (8/34) in the classic
      tension-free vaginal tape group, and 11.5% (3/26) in the open colposuspension
      group were continent. Repeated operative treatment was more frequent in the
      laparoscopic colposuspension (18.5%) and open colposuspension (30%) groups
      compared with the tension-free vaginal tape group (0%; P <= 0.003). Calculated
      scores from the questionnaire from all 3 groups indicated moderate to severe
      recurrent urinary incontinence with equal prevalence of symptoms of stress, urge,
      or mixed urinary incontinence. CONCLUSIONS: Subjective urinary continence 6 to 9
      years after primary operative treatment was low for all analyzed procedures.

PMID- 22983273
TI  - Condition-specific quality of life 24 months after retropubic and transobturator
      sling surgery for stress urinary incontinence.
AB  - AIMS: To compare quality of life (QoL) and factors associated with QoL change
      after retropubic (RMUS) and transobturator midurethral slings (TMUS) using the
      Incontinence Impact Questionnaire (IIQ) and the International Consultation on
      Incontinence Questionnaire (ICIQ). METHODS: Five hundred ninety-seven women in a
      multicenter randomized trial of RMUS versus TMUS were examined. The IIQ and the
      ICIQ were obtained at baseline and at 12 and 24 months. Repeated-measures
      analysis of variance tested for differences by treatment group over time.
      Multivariable analysis identified factors associated with QoL change at 12 months
      postoperative, controlling for treatment group and baseline QoL. RESULTS:
      Improvement in IIQ was associated with the following: treatment success, younger
      age, improvement in stress urinary incontinence (SUI) symptom severity, and
      bother (all P < 0.05). Improvement in ICIQ was associated with treatment success,
      younger age, improvement in SUI symptom severity and bother, lower body mass
      index, and no reoperation (all P < 0.05). Improvement of the IIQ was stable over
      time (P = 0.35) for both treatment groups (P = 0.66), whereas the ICIQ showed a
      small but clinically insignificant decline (P = 0.03) in both treatment groups (P
      = 0.51). CONCLUSIONS: Postoperative QoL was improved after RMUS and TMUS.
      Measures of QoL functioned similarly, although more surgically modifiable urinary
      incontinence factors predicted improvement with the IIQ.

PMID- 22983275
TI  - Characterizing the phenotype of advanced pelvic organ prolapse.
AB  - OBJECTIVE: Genetic studies require a clearly defined phenotype to reach valid
      conclusions. Our aim was to characterize the phenotype of advanced prolapse by
      comparing women with stage III to IV prolapse with controls without prolapse.
      METHODS: Based on the pelvic organ prolapse quantification examination, women
      with stage 0 to stage I prolapse (controls) and those with stage III to stage IV
      prolapse (cases) were prospectively recruited as part of a genetic epidemiologic
      study. Data regarding sociodemographics; medical, obstetric, and surgical
      history; family history; and body mass index were obtained by a questionnaire
      administered by a trained coordinator and abstracted from electronic medical
      records. RESULTS: There were 275 case patients with advanced prolapse and 206
      controls with stage 0 to stage I prolapse. Based on our recruitment strategy, the
      women were younger than the controls (64.7 +/- 10.1 vs 68.6 +/- 10.4 years;
      P<0.001); cases were also more likely to have had one or more vaginal deliveries
      (96.0% vs 82.0%; P<0.001). There were no differences in race, body mass index,
      and constipation. Regarding family history, cases were more likely to report that
      either their mother and/or sister(s) had prolapse (44.8% vs 16.9%, P<0.001). In a
      logistic regression model, vaginal parity (odds ratio, 4.05; 95% confidence
      interval, 1.67-9.85) and family history of prolapse (odds ratio, 3.74; 95%
      confidence interval, 2.16-6.46) remained significantly associated with advanced
      prolapse. CONCLUSIONS: Vaginal parity and a family history of prolapse are more
      common in women with advanced prolapse compared to those without prolapse. These
      characteristics are important in phenotyping advanced prolapse, suggesting that
      these data should be collected in future genetic epidemiologic studies.

PMID- 22983276
TI  - Delayed presentation of pseudoabscess secondary to injection of pyrolytic carbon
      coated beads bulking agent.
AB  - BACKGROUND: Periurethral masses after injection of Durasphere bulking material
      have been previously reported to occur within 12 to 18 months of administration
      of the agent. METHODS: We present a case report of an anterior vaginal wall mass
      resulting from a pseudoabscess containing Durasphere agent 5 years after
      injection. A literature review of urethral bulking agent complications and
      imaging is also provided. RESULTS: The patient's anterior vaginal wall mass was
      thought to be due to a pseudoabscess secondary to injection of bulking agent.
      Pelvic imaging was helpful both in identifying the mass and in surgical planning.
      The patient was successfully treated by outpatient transvaginal resection of the
      material. CONCLUSIONS: Urethral bulking agents, although generally safe and
      effective in the treatment of stress urinary incontinence, can lead to formation
      of pseudoabscesses. Although these are usually recognized within the first 18
      months after injection, they may not be identified until several years later.

PMID- 22983277
TI  - Vaginal approach to vesicovaginal fistula and vaginal vault prolapse preserving
      sexual function by Latzko repair and sacrospinous suspension.
AB  - The combination of vesicovaginal fistula and complete vaginal vault prolapse is
      rare. The only published treatment recommendations concern partial colpocleisis,
      an option that precludes intercourse. In this case report, we describe successful
      repair of this problem with a Latzko fistula repair and a concomitant Michigan 4
      wall sacrospinous ligament suspension: instead of curing the fistula, correcting
      the prolapse, and preserving sexual function.

PMID- 22983278
TI  - Use of a tissue expander to aid in a second urethrolysis:  a case report.
AB  - OBJECTIVES: To describe a novel approach of retropubic urethrolysis using
      placement of a tissue expander to prevent rescarring after previously failed
      vaginal urethrolysis in a patient with known extensive scar tissue.

PMID- 22983279
TI  - Urethral mesh erosion after single-incision mid-urethral sling.
AB  - BACKGROUND: This report aims to describe urethral mesh erosion after a single
      incision synthetic midurethral sling placement and to discuss possible causes for
      this complication. CASE: A 41-year-old woman presented with recurrent stress
      urinary incontinence after an anchored single-incision midurethral sling
      placement. Cystourethroscopy and translabial pelvic ultrasonography demonstrated
      the size and location of the injury. Mesh removal, urethral reconstruction, and
      Martius transposition flap were performed. The entire mesh removed was 24%
      shorter than the product before insertion. CONCLUSION: Mesh contraction may play
      an important role in delayed urinary tract injury especially after anchored
      synthetic midurethral sling placements.

PMID- 22983280
TI  - The second ESGAR consensus statement on CT colonography.
AB  - OBJECTIVE: To update quality standards for CT colonography based on consensus
      among opinion leaders within the European Society of Gastrointestinal and
      Abdominal Radiology (ESGAR). MATERIAL AND METHODS: A multinational European panel
      of nine members of the ESGAR CT colonography Working Group (representing six EU
      countries) used a modified Delphi process to rate their level of agreement on a
      variety of statements pertaining to the acquisition, interpretation and
      implementation of CT colonography. Four Delphi rounds were conducted, each at 2
      months interval. RESULTS: The panel elaborated 86 statements. In the final round
      the panelists achieved complete consensus in 71 of 86 statements (82 %).
      Categories including the highest proportion of statements with excellent
      Cronbach's internal reliability were colon distension, scan parameters, use of
      intravenous contrast agents, general guidelines on patient preparation, role of
      CAD and lesion measurement. Lower internal reliability was achieved for the use
      of a rectal tube, spasmolytics, decubitus positioning and number of CT data
      acquisitions, faecal tagging, 2D vs. 3D reading, and reporting. CONCLUSION: The
      recommendations of the consensus should be useful for both the radiologist who is
      starting a CTC service and for those who have already implemented the technique
      but whose practice may need updating.

PMID- 22983281
TI  - Fully automated derivation of coronary artery calcium scores and cardiovascular
      risk assessment from contrast medium-enhanced coronary CT angiography studies.
AB  - OBJECTIVES: Performance evaluation of a fully automated system for calculating
      computed tomography (CT) coronary artery calcium scores from contrast medium
      enhanced coronary CT angiography (cCTA) studies. METHODS: One hundred and twenty
      seven patients (58 +/- 11 years, 71 men) who had undergone cCTA as well as an
      unenhanced CT calcium scoring study where included. Calcium scores were computed
      from cCTA by an automated image processing algorithm and compared with calcium
      scores obtained by standard manual assessment of unenhanced CT calcium scoring
      studies. Results were compared vis-a-vis (1) absolute calcium score values, (2)
      age-, gender- and race-dependent percentiles, and (3) commonly used calcium score
      risk classification categories. RESULTS: One hundred and nineteen out of 127
      (93.7%) studies were successfully processed. Mean Agatston calcium score values
      obtained by traditional non-contrast CT calcium scoring studies and derived from
      contrast medium-enhanced cCTA did not significantly differ (235.6 +/- 430.5 vs
      262.0 +/- 499.5; P > 0.05). Calcium score risk categories and Multi-Ethnic Study
      of Atherosclerosis (MESA) percentiles showed very high correlation (Spearman rank
      correlation coefficient = 0.97, P < 0.0001/0.95, P < 0.0001) between the two
      approaches. CONCLUSIONS: Calcium score values automatically computed from cCTA
      are highly correlated with standard unenhanced CT calcium scoring studies. These
      results suggest a radiation dose- and time-saving potential when deriving calcium
      scores from cCTA studies without a preceding unenhanced CT calcium scoring study.

PMID- 22983282
TI  - Pre-treatment differences and early response monitoring of neoadjuvant
      chemotherapy in breast cancer patients using magnetic resonance imaging: a
      systematic review.
AB  - OBJECTIVES: To assess whether magnetic resonance imaging (MRI) can identify pre
      treatment differences or monitor early response in breast cancer patients
      receiving neoadjuvant chemotherapy. METHODS: PubMed, Cochrane library, Medline
      and Embase databases were searched for publications until January 1, 2012. After
      primary selection, studies were selected based on predefined inclusion/exclusion
      criteria. Two reviewers assessed study contents using an extraction form.
      RESULTS: In 15 studies, which were mainly underpowered and of heterogeneous study
      design, 31 different parameters were studied. Most frequently studied parameters
      were tumour diameter or volume, K(trans), K(ep), V(e), and apparent diffusion
      coefficient (ADC). Other parameters were analysed in only two or less studies.
      Tumour diameter, volume, and kinetic parameters did not show any pre-treatment
      differences between responders and non-responders. In two studies, pre-treatment
      differences in ADC were observed between study groups. At early response
      monitoring significant and non-significant changes for all parameters were
      observed for most of the imaging parameters. CONCLUSIONS: Evidence on
      distinguishing responders and non-responders to neoadjuvant chemotherapy using
      pre-treatment MRI, as well as using MRI for early response monitoring, is weak
      and based on underpowered study results and heterogeneous study design. Thus, the
      value of breast MRI for response evaluation has not yet been established. KEY
      POINTS: Few well-validated pre-treatment MR parameters exist that identify
      responders and non-responders. Eligible studies showed heterogeneous study
      designs which hampered pooling of data. Confounders and technical variations of
      MRI accuracy are not studied adequately. Value of MRI for response evaluation
      needs to be established further.

PMID- 22983283
TI  - Image quality of ultra-low radiation exposure coronary CT angiography with an
      effective dose <0.1 mSv using high-pitch spiral acquisition and raw data-based
      iterative reconstruction.
AB  - OBJECTIVES: We evaluated the potential of prospectively ECG-triggered high-pitch
      spiral acquisition with low tube voltage and current in combination with
      iterative reconstruction to achieve coronary CT angiography with sufficient image
      quality at an effective dose below 0.1 mSv. METHODS: Contrast-enhanced coronary
      dual source CT angiography (2 * 128 * 0.6 mm, 80 kV, 50 mAs) in prospectively ECG
      triggered high-pitch spiral acquisition mode was performed in 21 consecutive
      individuals (body weight <100 kg, heart rate <=60/min). Images were reconstructed
      with raw data-based filtered back projection (FBP) and iterative reconstruction
      (IR). Image quality was assessed on a 4-point scale (1 = no artefacts, 4 =
      unevaluable). RESULTS: Mean effective dose was 0.06 +/- 0.01 mSv. Image noise was
      significantly reduced in IR (128.9 +/- 46.6 vs. 158.2 +/- 44.7 HU). The mean
      image quality score was lower for IR (1.9 +/- 1.1 vs. 2.2 +/- 1.0, P < 0.0001).
      Of 292 coronary segments, 55 in FBP and 40 in IR (P = 0.12) were graded
      "unevaluable". In patients with a body weight <=75 kg, both in FBP and in IR, the
      rates of fully evaluable segments were significantly higher in comparison to
      patients >75 kg. CONCLUSIONS: Coronary CT angiography with an estimated effective
      dose <0.1 mSv may provide sufficient image quality in selected patients through
      the combination of high-pitch spiral acquisition and raw data-based iterative
      reconstruction.

PMID- 22983284
TI  - Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics
      of the P-glycoprotein substrate talinolol in healthy volunteers.
AB  - PURPOSE: To investigate the effects of repeated glycyrrhizin ingestion on the
      oral pharmacokinetics of talinolol, a probe drug for P-glycoprotein (P-gp)
      activity in humans. METHODS: Fourteen healthy adult male subjects were enrolled
      in a two-phase randomized crossover-design study. In each phase the volunteers
      received placebo or compound glycyrrhizin tablets (75 mg glycyrrhizin three times
      daily) for 6 days. On the seventh day, a single oral dose of 100 mg talinolol was
      administered, and blood samples were obtained to determine plasma talinolol
      concentrations, measured in plasma by high-performance liquid chromatography with
      an ultraviolet detector. Non-compartmental analysis was used to characterize
      talinolol plasma concentration-time profiles. All pharmacokinetics parameters
      were calculated using DAS ver. 2.1 software, and statistical analyses were
      performed with SPSS ver. 13.0 software. Analysis of variance was used to check
      the difference of the means of the pharmacokinetic parameters between the two
      treatments at a significance level of 0.05. RESULTS: All treatments were well
      tolerated during the study period. The geometric mean +/- standard deviation of
      the AUC(0-infinity) for talinolol treated by glycyrrhizin and talinolol treated
      by placebo was 2,218.3 +/- 724.3 and 1,988.2 +/- 649.2 ng.h/mL, respectively. The
      90 % confidence intervals for the ratio of adjusted geometric means
      (glycyrrhizin:placebo) for AUC(0-infinity) and C (max) fell wholly within the
      interval [80, 125]. Six days of glycyrrhizin treatment resulted in no significant
      alterations in the pharmacokinetic parameters (AUC(0-infinity), AUC(0-24), C
      (max), t (max), t (1/2)) for talinolol. CONCLUSIONS: Continuous glycyrrhizin
      administration had no induction effect on the expression of P-gp in our trial.
      Further research is needed to study the direct inhibition effect of glycyrrhizin
      on the function of P-gp with the simultaneous administration of both glycyrrhizin
      and P-gp substrate.

PMID- 22983285
TI  - Case-control study of an outbreak of acute toxoplasmosis in an industrial plant
      in the state of Sao Paulo, Brazil.
AB  - Foodborne diseases represent operational risks in industrial restaurants. We
      described an outbreak of nine clustered cases of acute illness resembling acute
      toxoplasmosis in an industrial plant with 2300 employees. These patients and
      another 36 similar asymptomatic employees were diagnosed with anti-T. gondii IgG
      titer and avidity by ELISA. We excluded 14 patients based on high IgG avidity and
      chronic toxoplasmosis: 13 from controls and one from acute disease other than T.
      gondii infection. We also identified another three asymptomatic employees with
      T.gondii acute infection and also anti-T. gondii IgM positive as remaining acute
      cases. Case control study was conducted by interview in 11 acute infections and
      20 negative controls. The ingestion of green vegetables, but not meat or water,
      was observed to be associated with the incidence of acute disease. These data
      reinforce the importance of sanitation control in industrial restaurants and also
      demonstrate the need for improvement in quality control regarding vegetables at
      risk for T. gondii oocyst contamination. We emphasized the accurate diagnosis of
      indexed cases and the detection of asymptomatic infections to determine the
      extent of the toxoplasmosis outbreak.

PMID- 22983286
TI  - Two sequential PCR amplifications for detection of Schistosoma mansoni in stool
      samples with low parasite load.
AB  - Schistosomiasis constitutes a major public health problem, with an estimated 200
      million individuals infected worldwide and 700 million people living in risk
      areas. In Brazil there are areas of high, medium and low endemicity. Studies have
      shown that in endemic areas with a low prevalence of Schistosoma infection the
      sensitivity of parasitological methods is clearly reduced. Consequently diagnosis
      is often impeded due to the presence of false-negative results. The aim of this
      study is to present the PCR reamplification (Re-PCR) protocol for the detection
      of Schistosoma mansoni in samples with low parasite load (with less than 100 eggs
      per gram (epg) of feces). Three methods were used for the lysis of the envelopes
      of the S. mansoni eggs and two techniques of DNA extraction were carried out.
      Extracted DNA was quantified, and the results suggested that the extraction
      technique, which mixed glass beads with a guanidine
      isothiocyanate/phenol/chloroform (GT) solution, produced good results. PCR
      reamplification was conducted and detection sensitivity was found to be five eggs
      per 500 mg of artificially marked feces. The results achieved using these methods
      suggest that they are potentially viable for the detection of Schistosoma
      infection with low parasite load.

PMID- 22983287
TI  - Acute respiratory viral infections in children in Rio de Janeiro and Teresopolis,
      Brazil.
AB  - The frequency of viral pathogens causing respiratory infections in children in
      the cities of Rio de Janeiro and Teresopolis was investigated. Nasal swabs from
      children with acute respiratory illnesses were collected between March 2006 and
      October 2007. Specimens were tested for viral detection by conventional (RT)-PCR
      and/or real time PCR. Of the 205 nasal swabs tested, 64 (31.2%) were positive for
      at least one of the viral pathogens. Single infections were detected in 56
      samples, 50 of those were caused by RNA viruses: 33 samples tested positive for
      rhinovirus, five for influenza A, five for metapneumovirus, four for coronavirus
      and, three for respiratory syncytial virus. For the DNA viruses, five samples
      were positive for bocavirus and one for adenovirus. Co-infections with these
      viruses were detected in eight samples. Our data demonstrate a high frequency of
      viral respiratory infections, emphasizing the need for a more accurate diagnosis
      particularly for the emerging respiratory viruses. The fact that the emerging
      respiratory viruses were present in 9.2% of the tested samples suggests that
      these viruses could be important respiratory pathogens in the country.

PMID- 22983288
TI  - Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in
      Sao Paulo city, Brazil.
AB  - TB is currently considered to be the most important infectious disease among HIV
      1-infected subjects in developing countries, such as Brazil. A retrospective
      analysis of TB cases was performed, occurring from January 1995 to December 2010
      in our cohort of 599 HIV positive patients. The primary outcome was the
      occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16
      years, among 599 HIV positive patients in an open cohort setting in the city of
      Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB
      diagnosis was 146 and 186 cells/mm3, respectively. The mean HIV viral load was
      5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was
      1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The
      probability of surviving up to 10 years after diagnosis was 75% for TB patients
      as opposed to 96% for patients with other, non-TB opportunistic diseases (p =
      0.03). TB can be considered a public health problem among people living with HIV
      in Brazil despite of the widespread use of antiretrovirals for the treatment of
      HIV infection/AIDS.

PMID- 22983289
TI  - Spatial distribution of dengue in the city of Cruzeiro, Sao Paulo State, Brazil:
      use of geoprocessing tools.
AB  - The aim of this article is to identify patterns in spatial distribution of cases
      of dengue fever that occurred in the municipality of Cruzeiro, State of Sao
      Paulo, in 2006. This is an ecological and exploratory study using the tools of
      spatial analysis in the preparation of thematic maps with data from Sinan-Net. An
      analysis was made by area, taking as unit the IBGE census, the analysis included
      four months in 2006 which show the occurrence of the disease in the city. The
      thematic maps were constructed by TerraView 3.3.1 software, the same software
      provided the values of the indicators of Global Moran (I M) every month and the
      Kernel estimation. In the year 2006, 691 cases of dengue were georeferenced (with
      a rate of 864.2 cases/100,000 inhabitants); the indicators of Moran and p-values
      obtained were I M = 0.080 (March) p = 0.11; I M = 0.285 (April) p = 0.01; I M =
      0.201 (May) p = 0.01 and I M = 0.002 (June) p = 0.57. The first cases were
      identified in the Northeast and Central areas of Cruzeiro and the recent cases,
      in the North, Northeast and Central. It was possible to identify census tracts
      where the epidemic began and how it occurred temporally and spatially in the
      city.

PMID- 22983290
TI  - Contamination of public parks and squares from Guarulhos (Sao Paulo State, Brazil
      ) by Toxocara spp. and Ancylostoma spp.
AB  - The contaminated soil with mammal feces is an important factor of risk to
      infection with zoonotic diseases. Amongst these zoonoses are visceral larva
      migrans and cutaneous larva migrans caused by Toxocara spp. and Ancylostoma spp.,
      respectively. The aim of this study was to assess the environmental contamination
      by Toxocara spp. eggs and hookworms (Ancylostoma spp.) in public parks and
      squares in the city of Guarulhos, a metropolitan area of Sao Paulo, Sao Paulo
      State, Brazil. Soil samples were collected, between September and December 2010,
      and examined using the centrifugal flotation technique with sodium dichromate and
      zinc sulphate as well as the modified Baermann method. Notably, 35 (74.5%) of the
      47 districts surveyed in Guarulhos possessed samples contaminated with Toxocara
      spp. and/or eggs or larvae of Ancylostoma spp. The frequency of Toxocara spp. and
      Ancylostoma spp. in the samples from public areas was 68.1% and 46.8%,
      respectively. Overall, the eastern side of Guarulhos is the region with the
      highest occurrence of causative agents of larva migrans. In all collection sites,
      the presence of feces from dogs and cats accompanied by their owners and stray
      animals were observed. Notably, it is important to adopt measures to control dog
      and cat breeding, to treat infected animals, and provide health education to the
      population.

PMID- 22983291
TI  - Pharmacological effects of Sapindus mukorossi.
AB  - Sapindus mukorossi is an extremely valuable medicinal plant, distributed in
      tropical and sub-tropical regions of Asia. The aim of present review is to form a
      short compilation of the phytochemical composition and pharmacological properties
      of this multipurpose tree. The main phytoconstituents isolated and identified
      from different parts of this plant are triterpenoidal saponins of oleanane,
      dammarane and tirucullane type. The structure and chemical names of all the types
      of triterpenoidal saponins reported in Sapindus mukorossi are included in this
      review. Many research studies have been conducted to prove the plant's potential
      as being spermicidal, contraceptive, hepatoprotective, emetic, anti-inflammatory
      and anti-protozoal. The present review highlights some of the salient
      pharmacological uses of Sapindus mukorossi.

PMID- 22983292
TI  - Molluscicidal and Mosquitocidal activities of the essential oils of Thymus
      capitatus Hoff. et Link. and Marrubium vulgare L.
AB  - Steam distillation of essential oils of aerial parts of Thymus capitatus and
      Marrubium vulgare L. collected at North cost of Egypt yielded 0.5% and 0.2%,
      respectively. Results of Gas chromatography-mass spectrometry analyses of the two
      samples identified 96.27% and 90.19% of the total oil composition for T.
      capitatus and M. vulgare, respectively. The two oil samples appeared dominated by
      the oxygenated constituents (88.22% for T. capitatus and 57.50% for M. vulgare),
      composed of phenols, mainly carvacrol (32.98%) and thymol (32.82%) in essential
      oil of T. capitatus, and thymol (34.55%) in essential oil of M. vulgare. It was
      evaluated the molluscicidal activity of T. capitatus and M. vulgare essential
      oils on adult and eggs of Biomphalaria alexandrina as well as their mosquitocidal
      activity on Culex pipiens. The LC50 and LC90 of T. capitatus essential oil
      against adult snails was 200 and 400 ppm/3hrs, respectively, while for M. vulgare
      it was 50 and 100 ppm/3hrs, respectively. Moreover, M. vulgare showed LC100
      ovicidal activity at 200 ppm/24 hrs while T. capitatus oil showed no ovicidal
      activity. It was verified mosquitocidal activity, with LC50 and LC90 of 100 and
      200 ppm/12hrs respectively for larvae, and 200 and 400 ppm/12hrs respectively for
      pupae of C. pipiens.

PMID- 22983293
TI  - Genetic control of mosquitoes: population suppression strategies.
AB  - Over the last two decades, morbidity and mortality from malaria and dengue fever
      among other pathogens are an increasing Public Health problem. The increase in
      the geographic distribution of vectors is accompanied by the emergence of viruses
      and diseases in new areas. There are insufficient specific therapeutic drugs
      available and there are no reliable vaccines for malaria or dengue, although some
      progress has been achieved, there is still a long way between its development and
      actual field use. Most mosquito control measures have failed to achieve their
      goals, mostly because of the mosquito's great reproductive capacity and genomic
      flexibility. Chemical control is increasingly restricted due to potential human
      toxicity, mortality in no target organisms, insecticide resistance, and other
      environmental impacts. Other strategies for mosquito control are desperately
      needed. The Sterile Insect Technique (SIT) is a species-specific and
      environmentally benign method for insect population suppression, it is based on
      mass rearing, radiation mediated sterilization, and release of a large number of
      male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers
      a solution to many of the drawbacks of traditional SIT that have limited its
      application in mosquitoes while maintaining its environmentally friendly and
      species-specific utility. The self-limiting nature of sterile mosquitoes tends to
      make the issues related to field use of these somewhat less challenging than for
      self-spreading systems characteristic of population replacement strategies. They
      also are closer to field use, so might be appropriate to consider first. The
      prospect of genetic control methods against mosquito vectored human diseases is
      rapidly becoming a reality, many decisions will need to be made on a national,
      regional and international level regarding the biosafety, social, cultural and
      ethical aspects of the use and deployment of these vector control methods.

PMID- 22983295
TI  - Analogies in medicine: picture frame and tapir's nose.

PMID- 22983294
TI  - Whipple's disease: rare disorder and late diagnosis.
AB  - Whipple's disease is a rare systemic infectious disorder caused by the bacterium
      Tropheryma whipplei. We report the case of a 61-year-old male patient who
      presented to emergency room complaining of asthenia, arthralgia, anorexia,
      articular complaints intermittent diarrhea, and a 10-kg weight loss in one year.
      Laboratory tests showed the following results: Hb = 7.5 g/dL, albumin = 2.5
      mg/dL, weight = 50.3 kg (BMI 17.4 kg/m2). Upper gastrointestinal endoscopy
      revealed areas of focal enanthema in the duodenum. An endoscopic biopsy was
      suggestive of Whipple's disease. Diagnosis was confirmed based on a positive
      serum polymerase chain reaction. Treatment was initiated with intravenous
      ceftriaxone followed by oral trimethoprim-sulfamethoxazole. After one year of
      treatment, the patient was asymptomatic, with Hb = 13.5 g/dL, serum albumin = 5.3
      mg/dL, and weight = 70 kg (BMI 24.2 kg/m2). Whipple's disease should be
      considered a differential diagnosis in patients with prolonged constitutional
      and/or gastrointestinal symptoms. Appropriate antibiotic treatment improves the
      quality of life of patients.

PMID- 22983296
TI  - Reactions of platinum(IV)-bound nitriles with isomeric nitroanilines: addition
      vs. substitution.
AB  - The platinum(IV) complex trans-[PtCl(4)(EtCN)(2)] reacts smoothly and under mild
      conditions with isomeric o-, m- and p-nitroanilines (NAs) yielding two different
      types of products depending on the NA isomer, viz. the nitroaniline complexes
      cis/trans-[PtCl(4)(NA)(2)] (cis/trans-1-3) and the amidine species trans
      [PtCl(4){NH=C(Et)NHC(6)H(4)NO(2)-m}(EtCN)] (4), trans
      [PtCl(4){NH=C(Et)NHC(6)H(4)NO(2)-m}(2)] (5) and trans
      [PtCl(4){NH=C(Et)NHC(6)H(4)NO(2)-p}(EtCN)] (6). Complexes 4 and 5 undergo
      cyclometalation, furnishing mer-[PtCl(3){NH=C(Et)NHC(6)H(3)NO(2)-m}(EtCN)] (7)
      and mer-[PtCl(3){NH=C(Et)NHC(6)H(4)NO(2)-m}{NH=C(Et)NHC(6)H(3)NO(2)-m}] (8),
      respectively. Moreover, 8 both in the solid state and in solution undergoes the
      second step of the cyclometalation, generating [PtCl(2){NH=C(Et)NHC(6)H(3)NO(2)
      m}(2)] (9). In 4, the nitrile ligand is highly reactive toward nucleophilic
      addition and it undergoes facile hydration accompanied by the elimination of the
      nitrile, thus producing cis-[PtCl(4)(NH(2)C(6)H(4)NO(2)-m){NH=C(OH)Et}] (10), or
      methanol addition providing trans-[PtCl(4){NH=C(Et)NHC(6)H(4)NO(2)
      m}{NH=C(Et)OMe}] (11). All compounds, besides 9, were characterized by C, H, and
      N elemental analyses, high-resolution ESI-MS, IR, (1)H and (13)C{(1)H} NMR
      spectroscopic techniques. Complex 9, which was not isolated as a pure compound,
      was identified in the reaction mixture by ESI-MS and (1)H and (13)C{(1)H} NMR
      spectroscopies. Complexes trans-1, trans-2, 4, 5, 6, 8, 10, and 11 were
      additionally studied by X-ray diffraction.

PMID- 22983297
TI  - Combined hyoid bone flap in laryngeal reconstruction after extensive partial
      laryngectomy for laryngeal cancer.
AB  - Patients undergoing extensive partial laryngectomy require laryngeal
      reconstruction to restore function. Several techniques have been described, but
      they are associated with complications such as laryngeal stenosis. The aim of
      this study was to describe a new technique of combined hyoid bone and thyrohyoid
      membrane flap in laryngeal reconstruction after tumor resection, and to evaluate
      outcome. Eight patients requiring an extensive vertical or frontal partial
      laryngectomy for cancer were enrolled. Following radical tumor resection,
      laryngeal reconstruction was performed using the hyoid bone with a thyrohyoid
      membrane flap. Postoperative recovery time, complications, vocal quality, and
      cancer outcome were evaluated. The procedure was successful in all patients.
      There were no deaths, and no reports of postoperative dyspnea or dysphagia.
      Decannulation was performed in all patients after a median duration of 3 days
      (range 2-5 days). Swallowing and respiratory function were satisfactory and
      laryngeal stenosis did not occur during the mean follow-up period of 30.5 months.
      One patient had a local recurrence and required a salvage operation. A combined
      hyoid bone and thyrohyoid membrane flap is a reliable and relatively safe
      procedure that can be successfully performed for laryngeal reconstruction after
      extensive vertical or frontal partial laryngectomy.

PMID- 22983299
TI  - Complex impacts of an invasive omnivore and native consumers on stream
      communities in California and Hawaii.
AB  - The effects of invasive species on native communities often depend on the
      characteristics of the recipient community and on the food habits of the invasive
      species, becoming complicated when the invader is omnivorous. In field enclosure
      experiments, we assessed the direct and interactive effects of an invasive
      omnivorous crayfish (Procambarus clarkii) and either native herbivorous snails
      (Physella gyrina) or shrimp (Atyoida bisulcata) on stream communities in
      California and Hawaii, respectively. Based on literature data and the
      characteristics of each study site, we predicted that crayfish would affect
      primarily algal-based trophic linkages in an open California stream but detritus
      based trophic linkages in a shaded Hawaiian stream, with trophic cascades
      mediated through crayfish effects on primary consumers being observed in both
      systems. As predicted, crayfish in California directly reduced periphyton,
      filamentous algae, sediment, and snail levels, but generated a cascade by
      decreasing snail densities and increasing periphyton biomass. Contrary to
      prediction, crayfish did not reduce total invertebrate biomass. As predicted,
      crayfish in Hawaii reduced leaf litter, filamentous algae, and benthic
      invertebrate biomass. Contrary to our predictions, however, a trophic cascade was
      not observed because shrimp did not affect periphyton levels, crayfish did not
      reduce shrimp abundance, and crayfish had greater negative impacts on filamentous
      algae than did shrimp. Our findings highlight that the same invasive species can
      generate different effects on disparate systems, probably as mediated through the
      availability of different food types, flexibility in the invasive species' food
      habits, and complex pathways of trophic interaction.

PMID- 22983300
TI  - Bayesian coalescent analysis of pandemic H1N1 influenza A virus circulating in
      the South American region.
AB  - The first influenza pandemic of this century was declared in April of 2009, with
      the emergence of a novel H1N1 influenza A virus strain (H1N1pdm). Understanding
      the evolution of H1N1pdm populations within the South American region is
      essential for studying global diversification, emergence, resistance and vaccine
      efficacy. In order to gain insight into these matters, we have performed a
      Bayesian coalescent Markov Chain Monte Carlo analysis of hemagglutinin (HA) and
      neuraminidase (NA) gene sequences of all available and comparable HA and NA
      sequences obtained from H1N1pdm IAV circulating in the South American region.
      High evolutionary rates and fast population growths characterize the population
      dynamics of H1N1pdm strains in this region of the world. A significant
      contribution of first codon position to the mean evolutionary rate was found for
      both genes studied, revealing a high contribution of non-synonymous substitutions
      to the mean substitution rate. In the 178days period covered by these studies,
      substitutions in all HA epitope regions can be observed. HA substitutions D239G/N
      and Q310H have been observed only in Brazilian patients. While substitution
      D239G/N is not particularly associated to a specific genetic lineage, all strains
      bearing substitution Q310H were assigned to clade 6, suggesting a founder effect.
      None of the substitutions found in the NA proteins of H1N1pdm strains isolated in
      South America appears sufficiently close to affect the drug binding pocket for
      the three NA inhibitor antivirals tested. A more detailed analysis of NA proteins
      revealed epitope differences among 2010 vaccine and H1N1pdm IAV strains
      circulating in the South American region.

PMID- 22983298
TI  - Caloric restriction: is mammalian life extension linked to p53?
AB  - Caloric restriction, that is limiting food intake, is recognized in mammals as
      the best characterized and most reproducible strategy for extending lifespan,
      retarding physiological aging and delaying the onset of age-associated diseases.
      The aim of this mini review is to argue that p53 is the connection in the
      abilities of both the Sirt-1 pathway and the TOR pathway to impact on longevity
      of cells and organisms. This novel, lifespan regulating function of p53 may be
      evolutionarily more ancient than its relatively recent role in apoptosis and
      tumour suppression, and is likely to provide many new insights into lifespan
      modulation.

PMID- 22983301
TI  - Rapid variance components-based method for whole-genome association analysis.
AB  - The variance component tests used in genome-wide association studies (GWAS)
      including large sample sizes become computationally exhaustive when the number of
      genetic markers is over a few hundred thousand. We present an extremely fast
      variance components-based two-step method, GRAMMAR-Gamma, developed as an
      analytical approximation within a framework of the score test approach. Using
      simulated and real human GWAS data sets, we show that this method provides
      unbiased estimates of the SNP effect and has a power close to that of the
      likelihood ratio test-based method. The computational complexity of our method is
      close to its theoretical minimum, that is, to the complexity of the analysis that
      ignores genetic structure. The running time of our method linearly depends on
      sample size, whereas this dependency is quadratic for other existing methods.
      Simulations suggest that GRAMMAR-Gamma may be used for association testing in
      whole-genome resequencing studies of large human cohorts.

PMID- 22983303
TI  - On the role of the mitochondrial 2-oxoglutarate dehydrogenase complex in amino
      acid metabolism.
AB  - Mitochondria are tightly linked to cellular nutrient sensing, and provide not
      only energy, but also intermediates for the de novo synthesis of cellular
      compounds including amino acids. Mitochondrial metabolic enzymes as generators
      and/or targets of signals are therefore important players in the distribution of
      intermediates between catabolic and anabolic pathways. The highly regulated 2
      oxoglutarate dehydrogenase complex (OGDHC) participates in glucose oxidation via
      the tricarboxylic acid cycle. It occupies an amphibolic branch point in the
      cycle, where the energy-producing reaction of the 2-oxoglutarate degradation
      competes with glutamate (Glu) synthesis via nitrogen incorporation into 2
      oxoglutarate. To characterize the specific impact of the OGDHC inhibition on
      amino acid metabolism in both plant and animal mitochondria, a synthetic analog
      of 2-oxoglutarate, namely succinyl phosphonate (SP), was applied to living
      systems from different kingdoms, both in situ and in vivo. Using a high
      throughput mass spectrometry-based approach, we showed that organisms possessing
      OGDHC respond to SP by significantly changing their amino acid pools. By
      contrast, cyanobacteria which lack OGDHC do not show perturbations in amino acids
      following SP treatment. Increases in Glu, 4-aminobutyrate and alanine represent
      the most universal change accompanying the 2-oxoglutarate accumulation upon OGDHC
      inhibition. Other amino acids were affected in a species-specific manner,
      suggesting specific metabolic rearrangements and substrate availability mediating
      secondary changes. Strong perturbation in the relative abundance of amino acids
      due to the OGDHC inhibition was accompanied by decreased protein content. Our
      results provide specific evidence of a considerable role of OGDHC in amino acid
      metabolism.

PMID- 22983302
TI  - Exome sequencing identifies MVK mutations in disseminated superficial actinic
      porokeratosis.
AB  - Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly
      inherited epidermal keratinization disorder whose etiology remains unclear. We
      performed exome sequencing in one unaffected and two affected individuals from a
      DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene
      located in previously defined linkage regions after filtering against existing
      SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into
      consideration the functional implications of the mutations. Sanger sequencing in
      57 individuals with familial DSAP and 25 individuals with sporadic DSAP
      identified MVK mutations in 33% and 16% of these individuals (cases),
      respectively. All 14 MVK mutations identified in our study were absent in 676
      individuals without DSAP. Our functional studies in cultured primary
      keratinocytes suggest that MVK has a role in regulating calcium-induced
      keratinocyte differentiation and could protect keratinocytes from apoptosis
      induced by type A ultraviolet radiation. Our results should help advance the
      understanding of DSAP pathogenesis.

PMID- 22983304
TI  - Metabolic chiral inversion of brivanib and its relevance to safety and
      pharmacology.
AB  - Brivanib alaninate is an orally administered alanine prodrug of brivanib, a dual
      inhibitor of the vascular endothelial growth factor (VEGF) and fibroblast growth
      factor (FGF) signaling pathways. It is currently in clinical trials for the
      treatment of hepatocellular carcinoma and colorectal cancer. Brivanib has a
      single asymmetric center derived from a secondary alcohol. The potential for
      chiral inversion was investigated in incubations with liver subcellular fractions
      and in animals and humans after oral doses of brivanib alaninate. Incubations of
      [14C]brivanib alaninate with liver microsomes and cytosols from rats, monkeys,
      and humans followed by chiral chromatography resulted in two radioactive peaks,
      corresponding to brivanib and its enantiomer. The percentage of the enantiomeric
      metabolite relative to brivanib in microsomal and cytosolic incubations of
      different species in the presence of NADPH ranged from 11.6 to 15.8 and 0.8 to
      3.1%, respectively. The proposed mechanism of inversion involves the oxidation of
      brivanib to a ketone metabolite, which is subsequently reduced to brivanib and
      its enantiomer. After oral doses of brivanib alaninate to rats and monkeys, the
      enantiomeric metabolite was a prominent drug-related component in plasma, with
      the percentages of area under the curve (AUC) at 94.7 and 39.7%, respectively,
      relative to brivanib. In humans, the enantiomeric metabolite was a minor
      circulating component, with the AUC <3% of brivanib. Pharmacological studies
      indicated that brivanib and its enantiomer had similar potency toward the
      inhibition of VEGF receptor-2 and FGF receptor-1 kinases. Because of low plasma
      concentration in humans, the enantiomeric metabolite was not expected to
      contribute significantly to target-related pharmacology of brivanib. Moreover,
      adequate exposure in the toxicology species suggested no specific safety concerns
      with respect to exposure to the enantiomeric metabolite.

PMID- 22983305
TI  - A gas phase perspective on the Lewis acidity of metal ions in aqueous solution.
AB  - A pattern of instability exhibited by solvated metal dications in the gas phase
      shows a remarkable correlation (covering 10 orders of magnitude) with the ability
      of the same metal ions to promote the release of protons in aqueous solution.

PMID- 22983306
TI  - Implications of the prostate intervention versus observation trial (PIVOT).

PMID- 22983307
TI  - Acute hydrocephalus following heroin induced leukoencephalopathy.

PMID- 22983308
TI  - Obstructive hydrocephalus mimicking a normal pressure condition as unusual
      presentation of basilar artery aneurysm: a case report.

PMID- 22983309
TI  - Decline in genetic influence on the co-occurrence of alcohol, marijuana, and
      nicotine dependence symptoms from age 14 to 29.
AB  - OBJECTIVE: Cross-sectional studies have demonstrated high rates of comorbidity
      among substance use disorders. However, few studies have examined the
      developmental course of incident comorbidity and how it changes from adolescence
      to adulthood. The authors examine patterns of comorbidity among substance use
      disorders to gain insight into the effect of shared versus specific etiological
      influences on measures of substance abuse and dependence. METHOD: The authors
      evaluated the pattern of correlations among nicotine, alcohol, and marijuana
      abuse and dependence symptom counts as well as their underlying genetic and
      environmental influences in a community-representative twin sample (N=3,762).
      Symptoms were assessed at ages 11, 14, 17, 20, 24, and 29 years. A single common
      factor was used to model the correlations among symptom counts at each age. The
      authors examined age-related changes in the influence of this general factor by
      testing for differences in the mean factor loading across time. RESULTS: Mean
      levels of abuse or dependence symptoms increased throughout adolescence, peaked
      around age 20, and declined from age 24 to age 29. The influence of the general
      factor was highest at ages 14 and 17, but decreased from age 17 to age 24.
      Genetic influences of the general factor declined considerably with age alongside
      an increase in nonshared environmental influences. CONCLUSIONS: Adolescent
      substance abuse or dependence is largely a function of shared etiology. As young
      people age, their symptoms are increasingly influenced by substance-specific
      etiological factors. Heritability analyses revealed that the generalized risk is
      primarily influenced by genetic factors in adolescence, but nonshared
      environmental influences increase in importance as substance dependence becomes
      more specialized in adulthood.

PMID- 22983310
TI  - Placebo? no thanks, it might be bad for me!
AB  - OBJECTIVE: To assess the potential damage to patients from the inappropriate use
      of placebo. METHODS: Pivotal clinical trials of new drugs were evaluated for the
      treatment of multiple sclerosis following effective treatment with beta
      interferons and glatiramer acetate. The differences in the relapse rate between
      the experimental arms of the trials with interferons and glatiramer and the
      placebo groups were calculated. RESULTS: In ten pivotal trials, 2,752 patients
      were given placebo instead of the best proven treatments. The annualized relapse
      rate was reported for 2,405 of these patients. Patients receiving placebo
      suffered 630 more relapses than those treated with interferons or glatiramer.
      CONCLUSIONS: The inappropriate use of placebo in clinical trials unduly harms
      patients. The use of standard active comparators would preserve patients' rights
      and better define the respective clinical value of new medicines.

PMID- 22983311
TI  - Treatment discontinuation with methylphenidate in adults with attention deficit
      hyperactivity disorder: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) in adulthood is
      increasingly diagnosed and treated. Methylphenidate is frequently advocated as a
      first-line pharmacological treatment. PURPOSE: The aim of our study was to
      compare all-cause discontinuation rate of methylphenidate and its pharmaceutical
      presentations with placebo in adults with ADHD. METHODS: This was a systematic
      review and meta-analysis of randomized controlled trials comparing
      methylphenidate with placebo in adults with ADHD. All-cause treatment
      discontinuation was the primary endpoint. The efficacy in reducing ADHD symptoms
      and safety were the secondary endpoints. RESULTS: Twelve studies (2,496 patients)
      met the inclusion criteria. Four racemic methylphenidate and one
      dexmethylphenidate presentations were investigated. The rate of all-cause
      treatment discontinuation was greater with methylphenidate than with placebo, but
      this difference was not statistically significant [odds ratio (OR) 1.19, 95 %
      confidence interval (95 % CI) 0.82-1.74, P = 0.37, I(2) = 64 %] This finding
      reached the conventional threshold of statistical significance after one outlier
      study was excluded (OR 1.44, 95 % CI 1.14-1.82, P = 0.002, I(2) = 0).
      Methylphenidate was more efficacious than placebo for reducing ADHD symptoms and
      it was associated with a higher proportion of patients dropping out due to
      adverse effects. CONCLUSIONS: Despite reducing ADHD symptoms, methylphenidate
      showed no advantage over placebo in terms of treatment discontinuation. More
      attention should be given in the future to the endpoint "all-cause treatment
      discontinuation" when making regulatory decisions and developing clinical
      guidelines involving the treatment of ADHD in adulthood.

PMID- 22983313
TI  - Letter to the editor.

PMID- 22983312
TI  - Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of
      peritoneal carcinomatosis.
AB  - PURPOSE: Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has
      not previously been measured with a selective technique. The primary aims were to
      examine the pharmacokinetics of active cisplatin and its monohydrated complex
      (MHC) during HIPEC using a specific measuring technique, to compare cisplatin's
      systemic absorption with oxaliplatin, and to compare active cisplatin levels to
      that of total platinum. METHODS: Ten patients treated with cytoreductive surgery
      and HIPEC (cisplatin 50 mg/m(2),doxorubicin 15 mg/m(2)) were recruited. Blood and
      perfusate samples were drawn during and after HIPEC. Cisplatin analysis was
      conducted using liquid chromatography (LC) with post-column derivatization with
      diethyldithiocarbamate and compared with inductively coupled plasma-mass
      spectrometry (ICP-MS). RESULTS: The mean half-life (t1/2) of perfusate cisplatin
      was 18.4 min, with area under the time-concentration curve (AUC) 0-90 min of 2.87
      mM.min and estimated 0-60 min of 2.45 mM.min. The absorption t1/2 was 9.0 min for
      cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active
      cisplatin increased in a linear manner by time of perfusion. CONCLUSIONS:
      Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60
      min does not significantly change the pharmacokinetics of cisplatin, and is
      therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS
      technique does not adequately reflect active cisplatin levels in the perfusate.

PMID- 22983314
TI  - Early implant bone loss:  preventable or inevitable?
AB  - Early implant bone loss (EIBL) is defined as the periimplant crestal bone loss
      occurring from fixture installation to 1 year after loading. This phenomenon has
      been suggested to be associated with biologic and biomechanical factors.
      Minimizing EIBL at every treatment step is preferable because this may improve
      implant health, aesthetics, and overall success. This review presents the host
      related factors, implant design characteristics, and the surgical and restorative
      protocol modifiers that should be evaluated during therapy. Host-related factors
      may involve the healing capacity, periodontal status, and occlusal function.
      Implant design features to be considered include the control of biologic width,
      microgap, and crestal stress distribution. Finally, surgical and restorative
      factors to be considered are implant site development, minimally invasive
      surgical approach, implant positioning, and the restorative design and occlusal
      scheme. Rationale and strategies to control the modifiable factors are also
      proposed.

PMID- 22983315
TI  - Labial bone thickness in area of anterior maxillary implants associated with
      crestal labial soft tissue thickness.
AB  - OBJECTIVE: To explore the relationship between implant's labial bone thickness
      (ILBT) and crestal labial soft tissue thickness (CLSTT). MATERIALS AND METHODS:
      This retrospective study used records of 32 (22 females and 10 males) patients
      who had 2 implants placed in their maxillary arch (64 implants; diameter range,
      3.3-4.6 mm) between the canines at either maxillary lateral incisor (7 and 10) or
      central incisor (8 and 9) region. All patients had diagnostic and postoperative
      cone beam computed tomography scans; the ILBT at the crestal and midimplant
      levels were recorded. CLSTT was measured approximately 4 months after the
      placement of implants using a digital caliper at the crestal level. RESULTS: Mean
      (standard deviation) CLSTT and ILBT at crestal and at midimplant levels were 2.45
      (0.88), 1.79 (0.68), and 2.33 (1.01) mm, respectively. Overall, 26 implants had
      prior bone augmentation. Significant relationships between the CLSTT and ILBT at
      crestal (Spearman's rho = 0.720) and midimplant levels (Spearman's rho = 0.707)
      were observed (P < 0.001). The determination coefficients (R) between CLSTT and
      ILBT at crestal and midimplant levels were 0.649 and 0.542, respectively.
      Following regression equations were produced: CLSTT = 1.043 * ILBT (crestal
      level) + 0.586 and CLSTT = 0.955 * ILBT (midimplant level) + 0.955. CONCLUSION:
      Based on this study, CLSTT and ILBT were highly associated in the anterior
      maxillary region.

PMID- 22983316
TI  - Placement of retrievable self-expandable metallic stents with barbs into patients
      with obstructive prostate cancer.
AB  - OBJECTIVES: To evaluate the technical feasibility and clinical effectiveness of
      retrievable self-expandable metallic stents with barbs in patients with
      obstructive prostate cancer. METHODS: Retrievable self-expandable metallic stents
      with eight barbs each were inserted into eight consecutive patients with
      obstructive prostate cancer. Patient ages ranged from 55 to 76 years (mean, 69
      years). All eight patients had previously received hormone therapy, and three had
      undergone palliative transurethral prostatectomy. Stents were removed using a 21
      F stent removal set if they caused complications. RESULTS: Stent placement was
      technically successful and well tolerated in all patients. One had severe
      incontinence, which improved spontaneously, and two had gross haematuria, which
      disappeared spontaneously within 4 days. Peak urine flow rates and post-void
      residual urine volumes 1 month after stent placement were 5.6-10.2 ml/s (mean,
      8.3 ml/s), and 5-45 ml (mean, 27 ml), respectively. During a mean follow-up of
      192 days (range, 39-632 days), one patient required stent removal after 232 days
      because of stone formation within the stent. No further intervention was required
      because the mass improved after stent removal. CONCLUSIONS: These preliminary
      results suggest that retrievable stents with eight barbs are both feasible to
      place and effective in patients with obstructive prostate cancer.

PMID- 22983317
TI  - Novel technology of multimodal ultrasound tomography detects breast lesions.
AB  - OBJECTIVES: To introduce a new three-dimensional (3D) diagnostic imaging
      technology, termed "multimodal ultrasonic tomography" (MUT), for the detection of
      breast cancer without ionising radiation or compression. METHODS: MUT performs 3D
      tomography of the pendulant breast in a water-bath using transmission ultrasound
      in a fixed-coordinate system. Specialised electronic hardware and signal
      processing algorithms are used to construct multimodal images for each coronal
      slice, corresponding to measurements of refractivity and frequency-dependent
      attenuation and dispersion. In-plane pixel size is 0.25 mm * 0.25 mm and the
      inter-slice interval can vary from 1 to 4 mm, depending on clinical requirements.
      MUT imaging was performed on 25 patients ("off-label" use for research purposes
      only), presenting lesions with sizes >10 mm. Histopathology of biopsy samples,
      obtained from all patients, were used to evaluate the MUT outcomes. RESULTS: All
      lesions (21 malignant and four benign) were clearly identified on the MUT images
      and correctly classified into benign and malignant based on their respective
      multimodal information. Malignant lesions generally exhibited higher values of
      refractivity and frequency-dependent attenuation and dispersion. CONCLUSION:
      Initial clinical results confirmed the ability of MUT to detect and differentiate
      all suspicious lesions with sizes >10 mm discernible in mammograms of 25 female
      patients.

PMID- 22983318
TI  - Structure and stability range of a hexanuclear Th(IV)-glycine complex.
AB  - A hexanuclear Th(IV)-glycine complex was observed by Th L(3)-edge EXAFS
      measurements in an aqueous solution. Within the stability range of this complex
      the positively charged hexanuclear species [Th(6)(MU(3)-O)(4)(MU(3)
      OH)(4)(H(2)O)(6)(Gly)(6)(HGly)(6)](6+) was preserved in a crystal with the
      composition [Th(6)(MU(3)-O)(4)(MU(3)
      OH)(4)(H(2)O)(6)(Gly)(6)(HGly)(6)].(NO(3))(3)(ClO(4))(3)(H(2)O)(3). This complex
      appears as a result of a competing reaction between hydrolysis and ligation by
      glycine. At a pH value below the stability range of the hexanuclear complex,
      crystals with the composition [Th(H(2)O)(3)(HGly)(3)].(ClO(4))(4)H(2)O were
      obtained from the solution. Three water molecules in the thorium coordination
      sphere indicate that this complex occurs prior to the onset of Th(IV) hydrolysis.

PMID- 22983319
TI  - Optimization, purification and characterization of novel thermostable,
      haloalkaline, solvent stable protease from Bacillus halodurans CAS6 using marine
      shellfish wastes: a potential additive for detergent and antioxidant synthesis.
AB  - A protease producing marine bacterium, Bacillus halodurans CAS6 isolated from
      marine sediments, was found to produce higher enzyme by utilizing shrimp shell
      powder. Optimum culture conditions for protease production were 50  degrees C, pH
      9.0, 30 % NaCl and 1 % shrimp shell powder (SSP) and the protease purified with a
      specific activity of 509.84 U/mg. The enzyme retained 100 % of its original
      activity even at 70  degrees C, pH 10.0 and 30 % NaCl for 1 h. The purified
      protease exhibited higher stability when treated with ionic, non-ionic (72-94 %)
      and commercial detergents (76-88 %), and organic solvents (88-126 %). Significant
      blood stain removal activity was found with the enzyme in washing experiments.
      The culture supernatant supplemented with 1 % SSP showed 93.67 +/- 2.52 %
      scavenging activity and FT-IR analysis of the reaction mixture confirmed the
      presence of antioxidants such as cyclohexane and cyclic depsipeptide with
      aliphatic amino groups. These remarkable qualities found with this enzyme
      produced by Bacillus halodurans CAS6 could make this as an ideal candidate to
      develop the industrial process for bioconversion of marine wastes and antioxidant
      synthesis.

PMID- 22983333
TI  - Personalized nanomedicine: paving the way to the practical clinical utility of
      genomics and nanotechnology advancements.

PMID- 22983351
TI  - Cigarette smoke and its component acrolein augment IL-8/CXCL8 mRNA stability via
      p38 MAPK/MK2 signaling in human pulmonary cells.
AB  - Interleukin-8 (IL-8/CXCL8) is an important neutrophil chemoattractant known to be
      elevated in the airways of cigarette smokers and in patients with chronic
      obstructive pulmonary disease (COPD). We examined the acute effect of aqueous
      cigarette smoke extract (CSE) on IL-8 expression in primary human pulmonary
      cells, in particular in normal human bronchial smooth muscle cells (HBSMCs). IL-8
      mRNA levels increased upon CSE exposure in a concentration- and time-dependent
      manner, and such an effect was accompanied by IL-8 secretion. CSE-evoked
      elevation of IL-8 mRNA was mimicked by its component acrolein. Both CSE and
      acrolein induced p38 mitogen-activated protein kinase (MAPK) phosphorylation,
      accompanied by the phosphorylation of MAPK-activated kinase 2 (MK2), a known
      downstream substrate of the p38 MAPK, both in HBSMCs and in human airway
      epithelial cells. Furthermore, pharmacological inhibition of p38 MAPK or MK2
      strongly accelerated the decay of IL-8 mRNA levels upon stimulation with CSE or
      acrolein and subsequent blockade of mRNA neosynthesis with actinomycin D in
      pulmonary structural cells (HBSMCs and airways epithelial cells) as well as in
      human alveolar macrophages. Conversely, pharmacological inhibition of ERK1/2
      signaling inhibited CSE-induced steady-state levels of IL-8 mRNA without
      affecting mRNA stability, thus suggesting inhibition at the transcriptional
      level. In sum, p38 MAPK/MK2 signaling is an important posttranscriptional
      mechanism underlying upregulation of IL-8 mRNA levels elicited by CSE and
      acrolein. Given the pivotal role of IL-8 in neutrophil chemotaxis and activation,
      our results shed light on the mechanisms through which cigarette smoke can
      initiate inflammation in the lung.

PMID- 22983350
TI  - delta ENaC: a novel divergent amiloride-inhibitable sodium channel.
AB  - The fourth subunit of the epithelial sodium channel, termed delta subunit (delta
      ENaC), was cloned in human and monkey. Increasing evidence shows that this unique
      subunit and its splice variants exhibit biophysical and pharmacological
      properties that are divergent from those of alpha ENaC channels. The widespread
      distribution of epithelial sodium channels in both epithelial and nonepithelial
      tissues implies a range of physiological functions. The altered expression of
      SCNN1D is associated with numerous pathological conditions. Genetic studies link
      SCNN1D deficiency with rare genetic diseases with developmental and functional
      disorders in the brain, heart, and respiratory systems. Here, we review the
      progress of research on delta ENaC in genomics, biophysics, proteomics,
      physiology, pharmacology, and clinical medicine.

PMID- 22983352
TI  - Maternal allergen exposure reprograms the developmental lung transcriptome in
      atopic and normoresponsive rat pups.
AB  - The "fetal origins hypothesis" argued that physiological changes consequent to in
      utero exposures ultimately contribute to disease susceptibility in later life.
      The dramatic increase in asthma prevalence is attributed to early exposures
      acting on preexisting asthma-susceptible genotypes. We showed previously that
      distinct transcriptome signatures distinguish the developmental respiratory
      phenotype of atopic (Brown Norway, BN) and normoresponsive (Lewis) rats. We aimed
      to determine whether maternal allergen exposure would influence asthma
      pathogenesis by reprogramming primary patterns of developmental lung gene
      expression. Postnatal offspring of dams sensitized to ovalbumin before mating and
      challenged during pregnancy were assessed for lung function, inflammatory
      biomarkers, and respiratory gene expression. Although maternal ovalbumin exposure
      resulted in characteristic features of an allergic response (bronchoalveolar
      lavage neutrophils, IgE, methacholine-induced lung resistance) in offspring of
      both strains, substantial strain-specific differences were observed in
      respiratory gene expression. Of 799 probes representing the top 5% of
      transcriptomic variation, only 112 (14%) were affected in both strains. Strain
      specific gene signatures also exhibited marked differences in enrichment for gene
      ontologies, with immune regulation and cell proliferation being prominent in the
      BN strain, cell cycle and microtubule assembly gene sets in the Lewis strain.
      Multiple ovalbumin-specific probes in both strains were also differentially
      expressed in lymphoblastoid cell lines from human asthmatic vs. nonasthmatic
      sibling pairs. Our data point to the existence of distinct, genetically
      programmed responses to maternal exposures in developing lung. These different
      response patterns, if recapitulated in human fetal development, can contribute to
      long-term pulmonary health including interindividual susceptibility to asthma.

PMID- 22983353
TI  - TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary
      emphysema.
AB  - Toll-like receptors (TLRs) exert important nonimmune functions in lung
      homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role
      of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and
      emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD)
      patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and
      their respective control strains were exposed to chronic CS or air. Human or
      mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were
      exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for
      autophagic or apoptotic proteins by Western blot analysis or confocal imaging.
      Chronic obstructive lung disease lung tissues and human pulmonary epithelial
      cells exposed to CSE displayed increased TLR4 expression, and increased
      autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic
      (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed
      increased expression of LC3B relative to control cells, basally and after
      exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved
      caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient
      mice. Wild-type mice subjected to chronic CS-exposure displayed airspace
      enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked
      increase in airspace relative to wild-type mice after CS-exposure. The Tlr4
      mutated or Tlr4-deficient mice showed higher levels of LC3B under basal
      conditions and after CS exposure. The expression of cleaved caspase-3 was
      markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective
      regulatory function of TLR4 against emphysematous changes of the lung in response
      to CS.

PMID- 22983354
TI  - Genetic disruption of protein kinase Cdelta reduces endotoxin-induced lung
      injury.
AB  - The pathogenesis of acute lung injury and acute respiratory distress syndrome is
      characterized by sequestration of leukocytes in lung tissue, disruption of
      capillary integrity, and pulmonary edema. PKCdelta plays a critical role in RhoA
      mediated endothelial barrier function and inflammatory responses. We used mice
      with genetic deletion of PKCdelta (PKCdelta(-/-)) to assess the role of PKCdelta
      in susceptibility to LPS-induced lung injury and pulmonary edema. Under baseline
      conditions or in settings of increased capillary hydrostatic pressures, no
      differences were noted in the filtration coefficients (k(f)) or wet-to-dry weight
      ratios between PKCdelta(+/+) and PKCdelta(-/-) mice. However, at 24 h after
      exposure to LPS, the k(f) values were significantly higher in lungs isolated from
      PKCdelta(+/+) than PKCdelta(-/-) mice. In addition, bronchoalveolar lavage fluid
      obtained from LPS-exposed PKCdelta(+/+) mice displayed increased protein and cell
      content compared with LPS-exposed PKCdelta(-/-) mice, but similar changes in
      inflammatory cytokines were measured. Histology indicated elevated LPS-induced
      cellularity and inflammation within PKCdelta(+/+) mouse lung parenchyma relative
      to PKCdelta(-/-) mouse lungs. Transient overexpression of catalytically inactive
      PKCdelta cDNA in the endothelium significantly attenuated LPS-induced endothelial
      barrier dysfunction in vitro and increased k(f) lung values in PKCdelta(+/+)
      mice. However, transient overexpression of wild-type PKCdelta cDNA in PKCdelta(-/
      ) mouse lung vasculature did not alter the protective effects of PKCdelta
      deficiency against LPS-induced acute lung injury. We conclude that PKCdelta plays
      a role in the pathological progression of endotoxin-induced lung injury, likely
      mediated through modulation of inflammatory signaling and pulmonary vascular
      barrier function.

PMID- 22983356
TI  - Comment on "Synthesis, functionalization and bioimaging applications of highly
      fluorescent carbon nanoparticles" by Sourov Chandra et al., Nanoscale, 2011, 3,
      1533.
AB  - A recent paper in this journal reported the synthesis of highly fluorescent
      crystalline carbon nanoparticles by microwave irradiation of sucrose with
      phosphoric acid. The emission wavelengths reported in this investigation are
      always twice the corresponding excitation wavelengths and the full widths at half
      maximum are extremely small (15-20 nm). We suggest that their results and
      discussions are questionable. Detailed analysis indicates that the fluorescence
      may not be real fluorescence, but the second order diffraction of excitation
      light.

PMID- 22983355
TI  - Individualized rTMS neuronavigated according to regional brain metabolism
      ((18)FGD PET) has better treatment effects on auditory hallucinations than
      standard positioning of rTMS: a double-blind, sham-controlled study.
AB  - Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of the left
      temporo-parietal cortex (LTPC) has been proposed as a useful therapeutic method
      for auditory hallucinations (AHs). Stereotactic neuronavigation enables the
      magnetic coil to be targeted according to the individual parameters obtained from
      neuroimaging. Individualized rTMS neuronavigated according to 18
      fluorodeoxyglucose positron emission tomography ((18)FDG PET) allows us to focus
      the coil explicitly on a given area with detected maxima of specific
      abnormalities, thus presuming a higher therapeutic effect of the method. The
      objective of this study is to test clinical efficacy of neuronavigated LF-rTMS
      administered according to the local maxima of (18)FDG PET uptake of LTPC and to
      compare it with treatment effects of standard and sham rTMS. In a double-blind,
      sham-controlled design, patients with AHs underwent a 10-day series of LF-rTMS
      using (1) (18)FDG PET-guided "neuronavigation," (2) "standard" anatomically
      guided positioning, and (3) sham coil. The effect of different rTMS conditions
      was assessed by the Auditory Hallucinations Rating Scale (AHRS) and the Positive
      and Negative Syndrome Scale (PANSS). Fifteen patients were randomized to a
      treatment sequence and ten of them completed all three treatment conditions. The
      intention-to-treat analysis of AHRS score change revealed superiority of the
      (18)FDG PET-guided rTMS over both the standard and the sham rTMS. The analyses of
      the PANSS scores failed to detect significant difference among the treatments.
      Our data showed acute efficacy of (18)FDG PET-guided rTMS in the treatment of
      AHs. Neuronavigated rTMS was found to be more effective than standard,
      anatomically guided rTMS. 

PMID- 22983357
TI  - Validation of the Patient Health Questionnaire (PHQ)-9 for prenatal depression
      screening.
AB  - The study was designed to validate the Patient Health Questionnaire (PHQ-9) for
      depression risk identification among pregnant women. Pregnant women were
      routinely administered the Prenatal Risk Overview, a comprehensive psychosocial
      screening interview, which included the PHQ-9, at their prenatal intake
      appointment at three community clinics. Study participants completed the
      Structured Clinical Interview for DSM-IV (SCID) at a later appointment. PHQ-9
      risk classifications were cross-tabulated with SCID diagnostic categories to
      examine concordance, sensitivity, specificity, and positive and negative
      predictive values. The study sample included 745 women. Prevalence of a current
      major depressive episode was 3.6 %; an additional 7.0 % were classified as
      meeting subdiagnostic criteria of three or more depressive symptoms. A PHQ-9
      score cutoff of 10 yielded sensitivity and specificity rates of 85 and 84 %,
      respectively, for a depression diagnosis and 75 and 88 % for a subdiagnosis,
      respectively. Positive predictive value was higher for the expanded group (43 %)
      than that of the diagnosis-only group (17 %). The PHQ-9, embedded within a
      multidimensional risk screening interview, effectively identified pregnant women
      who met criteria for current depression. The moderate risk score cutoff also
      identified women with subdiagnostic symptom levels who may benefit from
      interventions to alleviate their distress and improve pregnancy outcomes.

PMID- 22983358
TI  - A facile and versatile approach to biocompatible "fluorescent polymers" from
      polymerizable carbon nanodots.
AB  - Highly fluorescent polymerizable carbon nanodots (PCNDs), synthesized by
      microwave assisted pyrolysis and subsequent surface vinylation, were
      copolymerized with several model monomers to form different functional
      fluorescent polymeric materials in solution or the solid-state, indicating a
      simple and versatile approach to novel fluorescent polymer materials.

PMID- 22983359
TI  - The influence of age, sex, bulb position, visual feedback, and the order of
      testing on maximum anterior and posterior tongue strength and endurance in
      healthy belgian adults.
AB  - This study collected data on the maximum anterior and posterior tongue strength
      and endurance in 420 healthy Belgians across the adult life span to explore the
      influence of age, sex, bulb position, visual feedback, and order of testing.
      Measures were obtained using the Iowa Oral Performance Instrument (IOPI). Older
      participants (more than 70 years old) demonstrated significantly lower strength
      than younger persons at the anterior and the posterior tongue. Endurance remains
      stable throughout the major part of life. Gender influence remains significant
      but minor throughout life, with males showing higher pressures and longer
      endurance. The anterior part of the tongue has both higher strength and longer
      endurance than the posterior part. Mean maximum tongue pressures in this European
      population seem to be lower than American values and are closer to Asian results.
      The normative data can be used for objective assessment of tongue weakness and
      subsequent therapy planning of dysphagic patients.

PMID- 22983362
TI  - Pulse pressure, blood flow, and atherosclerosis.

PMID- 22983360
TI  - Monocytes-macrophages that express alpha-smooth muscle actin preserve primitive
      hematopoietic cells in the bone marrow.
AB  - Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone
      marrow stromal cell types. Here we identified rare activated bone marrow
      monocytes and macrophages with high expression of alpha-smooth muscle actin
      (alpha-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs.
      These myeloid cells resisted radiation-induced cell death and further upregulated
      COX-2 expression under stress conditions. COX-2-derived prostaglandin E(2)
      (PGE(2)) prevented HSPC exhaustion by limiting the production of reactive oxygen
      species (ROS) via inhibition of the kinase Akt and higher stromal-cell expression
      of the chemokine CXCL12, which is essential for stem-cell quiescence. Our study
      identifies a previously unknown subset of alpha-SMA(+) activated monocytes and
      macrophages that maintain HSPCs and protect them from exhaustion during alarm
      situations.

PMID- 22983366
TI  - Novel C,N-chelate rhodium(III) and iridium(III) antitumor complexes incorporating
      a lipophilic steroidal conjugate and their interaction with DNA.
AB  - The novel steroidal conjugates [M(eta(5)-C(5)Me(5))Cl(LEV-ppy)] (M = Rh (1) and
      Ir (2)) bearing the lipophilic levonorgestrel group 17-alpha-[2-phenylpyridyl-4
      ethynyl]-19-nortestosterone (LEV-ppy), where the chelating ligand is N and C
      bound, have been prepared and characterized. Both compounds are more active than
      cisplatin (about 6-fold) in T47D (breast cancer) at 48 h incubation time. On the
      other hand, very low resistance factors (RF) of 1 and 2 in A2780cisR (cisplatin
      resistant ovarian carcinoma) at 48 h were observed (RF = 0.9 and 1.1,
      respectively). The iridium steroidal compound 2 is twice as active as the non
      steroidal analogue 2', whose promising anticancer activity has recently been
      reported by Sadler. Theoretical DFT calculations on complexes 1 and 2 at the
      B3LYP-D/def2-TZVP-ecp level of theory show that the strongest bond to the metal
      atom is the eta(5)-interaction to the Cp* ligand and that both of them feature a
      rather strong metal-chlorine bond. The new steroidal conjugates 1 and 2 are able
      to bind to DNA according to Hoechst 33258 displacement experiments and ESI-TOF MS
      spectrometry studies. Complexes 1 and 2 are also cathepsin B inhibitors, an
      enzyme implicated in a number of cancer related events.

PMID- 22983367
TI  - Does body mass index in childhood predict restraint eating in early adolescence?
AB  - The aim of this study was (1) to examine whether childhood BMI is a significant
      predictor of restrained eating in preadolescents, (2) to investigate gender
      differences in restrained and emotional eating, and (3) to determine whether
      emotional problems, and body esteem were related to eating problems of
      preadolescents. In this longitudinal study with two measurement points, data from
      428 children (50% female) were used. At time 1 (t1) children were on average
      5.9years old. BMI was assessed using objective measures. At time 2 (t2)
      participants were 12years old. The adolescents and their parents completed
      questionnaires assessing restrained and emotional eating, body esteem, emotional
      problems, and BMI. Multiple regression analysis showed that restrained eating was
      significantly predicted by t1 BMI, by change in BMI between t1 and t2, and t2
      body esteem. Emotional eating was, as expected, not predicted by t1 BMI, but
      associated with t2 body esteem and t2 emotional problems. Gender was not a
      significant predictor. The stability of BMI between childhood and preadolescence
      and its ability to predict restrained eating suggests that it is important to
      start prevention of overweight, body dissatisfaction and disordered eating at an
      early age.

PMID- 22983368
TI  - Hervey, Harris, and the parabiotic search for lipostatic signals.
AB  - This paper is an introduction to the papers by Hervey and Harris that describe
      their experimental use of parabiosis in rats and mice to search for circulating
      lipostatic signals. Beginning in 1959 with Hervey's foundational paper, they
      detected three parabiotic signals: the Hervey signal decreases food intake and
      fat mass in rats; the antilipogenic factor (ALF) decreased fat mass, but not food
      intake in rats; and the leptin-dependent signal in lean partners of ob/ob mice
      decreased fat mass, but not food intake. The known lipostatic signals, leptin and
      insulin, have been candidates for the Hervey and ALF signals, but insulin has
      been excluded and the evidence for leptin is inconclusive. The site of production
      of the three parabiotic signals and their molecular structure are not known and
      specific mechanisms of their lipostatic control are incompletely understood.
      Given their potential importance for understanding the physiology of lipostatic
      controls and for developing new therapies for obesity, Hervey and Harris make a
      strong argument for further research on the three parabiotic signals.

PMID- 22983370
TI  - Acute infectious diarrhea lessons learned from the past?

PMID- 22983369
TI  - Plasma cortisol levels in response to a cold pressor test did not predict
      appetite or ad libitum test meal intake in obese women.
AB  - Heightened cortisol response to stress due to hyperactivation of the hypothalamic
      pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this
      study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as
      appetite ratings and subsequent test meal intake (TMI) in obese women. Following
      an overnight fast on two counterbalanced days, 20 obese women immersed their non
      dominant hand for 2min in ice water (CPT) or warm water (WW) as a control. Plasma
      cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress,
      pain, and appetite, were serially acquired. An ad libitum liquid meal was offered
      at 45min and intake measured covertly. Fasting cortisol was higher at 15min (mean
      peak cortisol) following the CPT compared to WW. Higher stress was reported at 2
      and 15min for the CPT compared to WW. Pain, an indirect marker of the acute
      stress, systolic and diastolic blood pressure increased following the CPT at 2min
      compared to WW. Hunger decreased after the CPT at 2 and 15min, and desire to eat
      ratings were lower following CPT compared to WW. Subjects did not have greater
      test meal intake (TMI) following CPT compared to WW. There was also no
      significant relationship between cortisol levels following stress and TMI,
      indicating that cortisol did not predict subsequent intake in obese women.

PMID- 22983371
TI  - World perspective on celiac disease.

PMID- 22983372
TI  - Viral hepatitis in children.

PMID- 22983373
TI  - Drug development: The use of unlicensed/off-label medicines in pediatrics.

PMID- 22983375
TI  - Hepatitis B and C:  Report of the FISPGHAN Working Group.

PMID- 22983376
TI  - Introduction to the FISPGHAN Working Group reports.

PMID- 22983377
TI  - Frequency of celiac disease in attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Although it is well known that celiac disease (CD) is associated with
      neurologic disorders, association with psychiatric problems is not well defined.
      In this report, we aimed to detect CD prevalence in patients with attention
      deficit hyperactivity disorder (ADHD). METHODS: A total of 362 patients between
      the ages 5 and 15 years with the diagnosis of ADHD according to the Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV
      TR) diagnostic criteria and 390 sex- and age-matched healthy children were
      included in the present study. Serum levels of tissue transglutaminase (tTg)
      immunoglobulin (Ig) A and IgG were studied in both groups. Serum IgA levels were
      also studied in patients with positive tTG IgG for the exclusion of selective IgA
      deficiency. Endoscopic duodenal biopsy was provided in seropositive patients,
      whose parents approved the procedure. Biopsy samples were evaluated according to
      Marsh-Oberhuber classification. RESULTS: tTg IgA was positive in 4 patients with
      ADHD (1.1%). Endoscopic duodenal biopsy was suggestive of CD in one of them
      (0.27%). tTg IgA was positive in 3 of control group patients (0.8%). Duodenal
      biopsy of the only patient from control group, who underwent upper
      gastrointestinal endoscopy, revealed normal intestinal mucosa. CONCLUSIONS: The
      seropositivity rates for CD were found similar in ADHD and control groups. Thus,
      neither routine screening for CD nor empirical recommendation of gluten-free diet
      seems necessary in children with ADHD.

PMID- 22983378
TI  - Serum retinol-binding protein 4 is independently associated with pediatric NAFLD
      and fasting triglyceride level.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is identified as a major
      liver disease in children. The present study aimed to identify the prevalence and
      predictors of pediatric NAFLD and the correlation between serum retinol-binding
      protein 4 (RBP4) levels and metabolic characteristics in children. METHODS: A
      total of 748 schoolchildren, ages 6 to 12 years, were enrolled in 2009. The body
      weight and height were measured in the morning before intake. Laboratory tests
      included overnight fasting serum lipids, insulin, liver enzymes, and RBP4 levels.
      Hepatic steatosis was determined by ultrasound in 219 volunteers. RESULTS: The
      rates of NAFLD were 3% in the normal-weight, 25% in the overweight, and 76% in
      the obese children. Twenty (22%) of obese children had abnormal alanine
      aminotransferase (ALT) levels. In children with NAFLD, younger age and higher
      body mass index (BMI), insulin/homeostasis model of assessment, and male sex rate
      were associated with abnormal liver function. Stepwise increments in BMI,
      insulin, homeostasis model of assessment, and ALT were found in children with
      normal livers to simple steatosis, and to steatosis with abnormal ALT. Multiple
      logistic regression analysis confirmed that serum RBP4 levels (P = 0.048), ALT (P
      = 0.048), and BMI (P < 0.001) were independently predictors of pediatric NAFLD.
      Moreover, multiple linear regression analysis revealed that only serum
      triglycerides levels were positively related to RBP4 levels (P < 0.001).
      CONCLUSIONS: Higher RBP4 and ALT levels as well as BMI are independently
      associated with pediatric NAFLD in Taiwan. In addition, an increment in RBP4
      levels was positively correlated to hypertriglyceridemia in children.

PMID- 22983379
TI  - Acute gastroenteritis disease: Report of the FISPGHAN Working Group.

PMID- 22983380
TI  - Malnutrition: Report of the FISPGHAN Working Group.

PMID- 22983381
TI  - Increased prevalence of antibodies against dietary proteins in children and young
      adults with cerebral palsy.
AB  - OBJECTIVES: Undernourishment is common in children with cerebral palsy (CP), but
      the reasons are unknown. We previously reported elevated levels of immunoglobulin
      (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG)
      in 99 children and young adults with CP without characteristic findings of gluten
      enteropathy in small bowel biopsies. Our aim was to perform a case-control study
      of IgG antibodies against other dietary antigens, AGA, anti-tTG, and IgE
      antibodies against wheat and gluten. METHODS: Sera from 99 cases with CP and 99
      healthy, age- and sex-matched controls were analysed with fluorescence enzyme
      linked immunosorbent assay for detection of IgG antibodies against beta
      lactoglobulin, casein, egg white, IgG- and IgA-AGA, IgA-anti-tTG, and IgE
      antibodies against gluten and wheat. RESULTS: Compared with controls, the odds
      ratio in cases with CP for having elevated levels of IgG antibodies against beta
      lactoglobulin was 17.0 (95% confidence interval [CI] 2.3-128), against casein
      11.0 (95% CI 2.6-46.8), and against egg white 7.0 (95% CI 1.6-30.8). The IgE
      responses for wheat/gluten were generally low. The tetraplegic and dyskinetic CP
      subtypes had significantly higher frequencies of elevated levels for all of the
      tested antibodies except IgG against egg white, and IgA-anti-tTG. A significantly
      lower weight was seen in cases with CP with positive versus negative serology.
      CONCLUSIONS: Elevated levels of IgG against dietary antigens were more frequent
      in the CP group compared with controls, and particularly in the tetraplegic and
      dyskinetic CP subtypes with the most severe neurologic handicap and
      undernourishment. Hypothetically, malnourishment may cause increased intestinal
      permeability and thus immunization against dietary antigens.

PMID- 22983382
TI  - Targeting lentiviral vectors for cancer immunotherapy.
AB  - Delivery of tumour-associated antigens (TAA) in a way that induces effective,
      specific immunity is a challenge in anti-cancer vaccine design. Circumventing
      tumour-induced tolerogenic mechanisms in vivo is also critical for effective
      immunotherapy. Effective immune responses are induced by professional antigen
      presenting cells, in particular dendritic cells (DC). This requires presentation
      of the antigen to both CD4(+) and CD8(+) T cells in the context of strong co
      stimulatory signals. Lentiviral vectors have been tested as vehicles, for both ex
      vivo and in vivo delivery of TAA and/or activation signals to DC, and have been
      demonstrated to induce potent T cell mediated immune responses that can control
      tumour growth. This review will focus on the use of lentiviral vectors for in
      vivo gene delivery to DC, introducing strategies to target DC, either targeting
      cell entry or gene expression to improve safety of the lentiviral vaccine or
      targeting dendritic cell activation pathways to enhance performance of the
      lentiviral vaccine. In conclusion, this review highlights the potential of
      lentiviral vectors as a generally applicable 'off-the-shelf' anti-cancer
      immunotherapeutic.

PMID- 22983383
TI  - Control by a hair's breadth: the role of microRNAs in the skin.
AB  - MicroRNAs have continued to attract enormous interest in the scientific community
      ever since their discovery. Their allure stems from their unique role in
      posttranscriptional gene expression control as well as their potential
      application as therapeutic targets in various disease pathologies. While much is
      known concerning their general biological function, such as their interaction
      with RNA-induced silencing complexes, many important questions still remain
      unanswered, especially regarding their functions in the skin. In this review, we
      summarize our current knowledge of the role of microRNAs in the skin in order to
      shine new light on our understanding of cutaneous biology and emphasize the
      significance of these small, single-stranded RNA molecules in the largest organ
      of the human body. Key events in epidermal and hair follicle biology, including
      differentiation, proliferation, and pigmentation, all involve microRNAs. We
      explore the role of microRNAs in several cutaneous processes, such as appendage
      formation, wound-healing, epithelial-mesenchymal transition, carcinogenesis,
      immune response, and aging. In addition, we discuss current trends in research
      and offer suggestions for future studies.

PMID- 22983385
TI  - Effects of MACPF/CDC proteins on lipid membranes.
AB  - Recent work on the MACPF/CDC superfamily of pore-forming proteins has focused on
      the structural analysis of monomers and pore-forming oligomeric complexes. We set
      the family of proteins in context and highlight aspects of their function which
      the direct and exclusive equation of oligomers with pores fails to explain.
      Starting with a description of the distribution of MACPF/CDC proteins across the
      domains of life, we proceed to show how their evolutionary relationships can be
      understood on the basis of their structural homology and re-evaluate models for
      pore formation by perforin, in particular. We furthermore highlight data showing
      the role of incomplete oligomeric rings (arcs) in pore formation and how this can
      explain small pores generated by oligomers of proteins belonging to the family.
      We set this in the context of cell biological and biophysical data on the
      proteins' function and discuss how this helps in the development of an
      understanding of how they act in processes such as apicomplexan parasites gliding
      through cells and exiting from cells.

PMID- 22983384
TI  - The exportomer: the peroxisomal receptor export machinery.
AB  - Peroxisomes constitute a dynamic compartment of almost all eukaryotic cells.
      Depending on environmental changes and cellular demands peroxisomes can acquire
      diverse metabolic roles. The compartmentalization of peroxisomal matrix enzymes
      is a prerequisite to carry out their physiologic function. The matrix proteins
      are synthesized on free ribosomes in the cytosol and are ferried to the
      peroxisomal membrane by specific soluble receptors. Subsequent to cargo release
      into the peroxisomal matrix, the receptors are exported back to the cytosol to
      facilitate further rounds of matrix protein import. This dislocation step is
      accomplished by a remarkable machinery, which comprises enzymes required for the
      ubiquitination as well as the ATP-dependent extraction of the receptor from the
      membrane. Interestingly, receptor ubiquitination and dislocation are the only
      known energy-dependent steps in the peroxisomal matrix protein import process.
      The current view is that the export machinery of the receptors might function as
      molecular motor not only in the dislocation of the receptors but also in the
      import step of peroxisomal matrix protein by coupling ATP-dependent removal of
      the peroxisomal import receptor with cargo translocation into the organelle. In
      this review we will focus on the architecture and function of the peroxisomal
      receptor export machinery, the peroxisomal exportomer.

PMID- 22983386
TI  - Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies.
AB  - OBJECTIVE: The authors performed a comprehensive meta-analysis of task-based
      functional MRI studies of attention deficit hyperactivity disorder (ADHD).
      METHOD: The authors searched PubMed, Ovid, EMBASE, Web of Science, ERIC, CINAHAL,
      and NeuroSynth for studies published through June 30, 2011. Significant
      differences in brain region activation between individuals with ADHD and
      comparison subjects were detected using activation likelihood estimation meta
      analysis. Dysfunctional regions in ADHD were related to seven reference neuronal
      systems. The authors performed a set of meta-analyses focused on age groups
      (children and adults), clinical characteristics (history of stimulant treatment
      and presence of psychiatric comorbidities), and specific neuropsychological tasks
      (inhibition, working memory, and vigilance/attention). RESULTS: Fifty-five
      studies were included (39 for children and 16 for adults). In children,
      hypoactivation in ADHD relative to comparison subjects was observed mostly in
      systems involved in executive function (frontoparietal network) and attention
      (ventral attentional network). Significant hyperactivation in ADHD relative to
      comparison subjects was observed predominantly in the default, ventral attention,
      and somatomotor networks. In adults, ADHD-related hypoactivation was predominant
      in the frontoparietal system, while ADHD-related hyperactivation was present in
      the visual, dorsal attention, and default networks. Significant ADHD-related
      dysfunction largely reflected task features and was detected even in the absence
      of comorbid mental disorders or a history of stimulant treatment. CONCLUSIONS: A
      growing literature provides evidence of ADHD-related dysfunction in multiple
      neuronal systems involved in higher-level cognitive functions but also in
      sensorimotor processes, including the visual system, and in the default network.
      This meta-analytic evidence extends early models of ADHD pathophysiology that
      were focused on prefrontal-striatal circuits.

PMID- 22983387
TI  - Significant variation of resected meso-esophageal tissue volume in two-stage
      subtotal esophagectomy specimens: a retrospective morphometric study.
AB  - BACKGROUND: Differences in the extent and quality of surgical resection for
      esophageal cancer may influence the pathological staging and patient outcome.
      There are no data in the literature qualitatively and/or quantitatively
      characterizing esophagectomy specimens. METHODS: Macroscopic images of 161
      esophagectomy specimens were analyzed retrospectively. The extent of resection
      was qualitatively classified as "muscularis propria," "intra-meso-esophageal," or
      "meso-esophageal." The volume of meso-esophageal tissue was quantified
      morphometrically. The number of muscle defects per specimen was counted. Results
      were related to clinicopathological variables, including survival. RESULTS: Sixty
      two (39%) specimens were classified as "muscularis propria," 65 (40%) as "intra
      meso-esophageal," and 34 (21%) as "meso-esophageal." The morphometrically
      measured meso-esophageal tissue volume was different between the three types (P <
      0.001). The specimen type was related to the total number of lymph nodes (P =
      0.02), number of metastatic lymph nodes (P = 0.024), and depth of tumor invasion
      (P = 0.013), but not related to extramural tumor volume, circumferential
      resection margin status, or the surgeon performing the resection. The number of
      muscle defects per specimen was similar in all resection types. The resection
      specimen classification was related to survival in patients treated by surgery
      alone (P = 0.027). CONCLUSIONS: This is the first study to quantify and classify
      the volume of tissue resected during esophagectomy. Our study shows significant
      variation of the resected tissue volume impacting pathological tumor staging.
      This variation was not associated with individual surgeon performance. A
      prospective, multicenter study is needed to validate our results and to
      investigate the potential biological mechanisms influencing the resectable volume
      of meso-esophageal tissue in cancer patients.

PMID- 22983388
TI  - Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC
      patients receiving cisplatin-based chemotherapy.
AB  - AIM: To investigate the expression profile of microRNAs in inoperable advanced
      non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the
      potential relevance of microRNAs to clinicopathological characteristics and
      prognosis. METHODS: Serum samples were taken from 260 inoperable advanced NSCLC
      patients and 260 healthy individuals. All the patients received cisplatin-based
      chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The
      serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were
      determined by quantitative real-time PCR. RESULTS: Serum levels of the 4
      microRNAs examined in NSCLC patients were significantly increased as compared
      with healthy individuals. The levels of miR-125b and miR-155 were changed in a
      similar pattern: the patients with stage IV disease had the highest one, while
      the patients with stage III A and stage III B disease showed similar increased
      levels. The levels of miR-10b and miR-34a in the patients with different stages
      were increased to similar extent. The level of miR-125b in poorly differentiated
      cancer was significantly higher than those in well and moderately differentiated
      cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly
      differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b
      was significantly associated with therapeutic response, exhibiting higher
      expression levels in non-responsive patients. Furthermore, the high level of miR
      125b was significantly correlated with poor patient survival. A multivariate Cox
      regression analysis showed that the expression level of miR-125b was an
      independent prognostic marker in NSCLC patients. CONCLUSION: Our results suggest
      that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This
      finding has important implications for development of targeted therapeutics to
      overcome chemotherapeutic resistance in NSCLC.

PMID- 22983390
TI  - Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro.
AB  - AIM: Filamin binding LIM protein 1, also known as migfilin, is a skeleton
      organization protein that binds to mitogen-inducible gene 2 at cell-extracellular
      matrix adhesions. The aim of this study was to investigate the role of migfilin
      in cisplatin-induced apoptosis in human glioma cells, to determine the functional
      domains of migfilin, and to elucidate the molecular mechanisms underlying the
      regulation of cisplatin-related chemosensitivity. METHODS: The human glioma cell
      lines Hs683, H4, and U-87 MG were transfected with pEGFP-C2-migfilin to elevate
      the expression level of migfilin. RNA interference was used to reduce the
      expression of migfilin. To determine the functional domains of migfilin, U-87 MG
      cells were transfected with plasmids of migfilin deletion mutants. After
      treatment with cisplatin (40 MUmol/L) for 24 h, the cell viability was assessed
      using the MTS assay, and the cell apoptotic was examined using the DAPI staining
      assay and TUNEL analysis. Expression levels of apoptosis-related proteins were
      detected by Western blot analysis. RESULTS: Overexpression of migfilin
      significantly enhanced cisplatin-induced apoptosis in Hs683, H4, and U-87 MG
      cells, whereas downregulation of migfilin expression inhibited the
      chemosensitivity of these cell lines. The N-terminal region of migfilin alone was
      able to enhance the cisplatin-induced apoptosis. However, despite the existence
      of the N-terminal region, mutants of migfilin with any one of three LIM domains
      deleted led to a function loss. Furthermore, apoptotic proteins (PARP and caspase
      3) and the anti-apoptotic protein Bcl-xL were modulated by the expression level
      of migfilin in combination with cisplatin. CONCLUSION: The LIM1-3 domains of
      migfilin play a key role in sensitizing glioma cells to cisplatin-induced
      apoptosis through regulation of apoptosis-related proteins.

PMID- 22983392
TI  - Luteolin reduces the invasive potential of malignant melanoma cells by targeting
      beta3 integrin and the epithelial-mesenchymal transition.
AB  - AIM: To investigate whether luteolin, a highly prevalent flavonoid, reverses the
      effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to
      determine the mechanisms underlying this reversal. METHODS: Murine malignant
      melanoma B16F10 cells were exposed to 1% O(2) for 24 h. Cellular mobility and
      adhesion were assessed using Boyden chamber transwell assay and cell adhesion
      assay, respectively. EMT-related proteins, such as E-cadherin and N-cadherin,
      were examined using Western blotting. Female C57BL/6 mice (6 to 8 weeks old) were
      injected with B16F10 cells (1*10(6) cells in 0.2 mL per mouse) via the lateral
      tail vein. The mice were treated with luteolin (10 or 20 mg/kg, ip) daily for 23
      d. On the 23rd day after tumor injection, the mice were sacrificed, and the lungs
      were collected, and metastatic foci in the lung surfaces were photographed.
      Tissue sections were analyzed with immunohistochemistry and HE staining. RESULTS:
      Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like
      to mesenchymal-like strips, which was accompanied by increased cellular adhesion
      and invasion. Luteolin (5-50 MUmol/L) suppressed the hypoxia-induced changes in
      the cells in a dose-dependent manner. Hypoxia significantly decreased the
      expression of E-cadherin while increased the expression of N-cadherin in the
      cells (indicating the occurrence of EMT-like transformation), which was reversed
      by luteolin (5 MUmol/L). In B16F10 cells, luteolin up-regulated E-cadherin at
      least partly via inhibiting the beta3 integrin/FAK signal pathway. In
      experimental metastasis model mice, treatment with luteolin (10 or 20 mg/kg)
      reduced metastatic colonization in the lungs by 50%. Furthermore, the treatment
      increased the expression of E-cadherin while reduced the expression of vimentin
      and beta3 integrin in the tumor tissues. CONCLUSION: Luteolin inhibits the
      hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the
      regulation of beta3 integrin, suggesting that luteolin may be applied as a
      potential anticancer chemopreventative and chemotherapeutic agent.

PMID- 22983391
TI  - Effects of propofol on ischemia-induced ventricular arrhythmias and mitochondrial
      ATP-sensitive potassium channels.
AB  - AIM: To investigate the potential of propofol in suppressing ventricular
      arrhythmias and to examine whether mitochondrial ATP-sensitive potassium channels
      are involved. METHODS: Male Sprague-Dawley rats were pretreated with intravenous
      infusion of propofol (Prop), a selective mitochondrial KATP channel inhibitor 5
      hydroxydecanoate (5-HD), propofol plus 5-HD (Prop+5-HD), a potent mitochondrial
      K(ATP) channel opener diazoxide (DZ) or NS, respectively. The dosage of each drug
      was 10 mg/kg. The animals then underwent a 30 min-ligation of the left anterior
      descending artery. The severity of arrhythmias, the incidence of ventricular
      fibrillation (VF), and the time of the first run of ventricular arrhythmias were
      documented using an arrhythmia scoring system. Mitochondrial membrane potential
      (DeltaPsim) was measured in freshly isolated rat cardiomyocytes with a
      fluorescence microscope. RESULTS: The arrhythmia scores in the Prop and DZ group
      were 2.6(0-5) and 2.4(0-5), respectively, which were significantly lower than
      that in the control group [4.9(2-8)]. VF was not observed in both Prop and DZ
      groups. The first run of ventricular arrhythmias was significantly postponed in
      the Prop group (10.5+/-2.2 vs 7.3+/-1.9 min). Bracketing of propofol with 5-HD
      eliminated the anti-arrhythmic effect of propofol. In isolated rat
      cardiomyocytes, propofol (50 MUmol/L) significantly decreased DeltaPsim, but when
      propofol was co-administered with 5-HD, the effect on DeltaPsim was reversed.
      CONCLUSION: Propofol preconditioning suppresses ischemia-induced ventricular
      arrhythmias in the rat heart, which are proposed to be caused by opening of
      mitochondrial K(ATP) channels.

PMID- 22983393
TI  - Toll-like receptor 3 agonist Poly I:C protects against simulated cerebral
      ischemia in vitro and in vivo.
AB  - AIM: To examine the neuroprotective effects of the Toll-like receptor 3 (TLR3)
      agonist Poly I:C in acute ischemic models in vitro and in vivo. METHODS: Primary
      astrocyte cultures subjected to oxygen-glucose deprivation (OGD) were used as an
      in vitro simulated ischemic model. Poly I:C was administrated 2 h before OGD.
      Cell toxicity was measured using MTT assay and LDH leakage assay. The levels of
      TNFalpha, IL-6 and interferon-beta (IFNbeta) in the media were measured using
      ELISA. Toll/interleukin receptor domain-containing adaptor-inducing IFNbeta
      (TRIF) protein levels were detected using Western blot analysis. A mouse middle
      cerebral artery occlusion (MCAO) model was u sed for in vivo study. The animals
      were administered Poly I:C (0.3 mg/kg, im) 2 h before MCAO, and examined with
      neurological deficit scoring and TTC staining. The levels of TNFalpha and IL-6 in
      ischemic brain were measured using ELISA. RESULTS: Pretreatment with Poly I:C (10
      and 20 MUg/mL) markedly attenuated OGD-induced astrocyte injury, and
      significantly raised the cell viability and reduced the LDH leakage. Poly I:C
      significantly upregulated TRIF expression accompanied by increased downstream
      IFNbeta production. Moreover, Poly I:C significantly suppressed the pro
      inflammatory cytokines TNFalpha and IL-6 production. In mice subjected to MCAO,
      administration of Poly I:C significantly attenuated the neurological deficits,
      reduced infarction volume, and suppressed the increased levels of TNFalpha and IL
      6 in the ischemic striatum and cortex. CONCLUSION: Poly I:C pretreatment exerts
      neuroprotective and anti-inflammatory effects in the simulated cerebral ischemia
      models, and the neuroprotection is at least in part due to the activation of the
      TLR3-TRIF pathway.

PMID- 22983389
TI  - PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes.
AB  - The PI3K-Akt pathway is a vital regulator of cell proliferation and survival.
      Alterations in the PIK3CA gene that lead to enhanced PI3K kinase activity have
      been reported in many human cancer types, including cancers of the colon, breast,
      brain, liver, stomach and lung. Deregulation of PI3K causes aberrant Akt
      activity. Therefore targeting this pathway could have implications for cancer
      treatment. The first generation PI3K-Akt inhibitors were proven to be highly
      effective with a low IC(50), but later, they were shown to have toxic side
      effects and poor pharmacological properties and selectivity. Thus, these
      inhibitors were only effective in preclinical models. However, derivatives of
      these first generation inhibitors are much more selective and are quite effective
      in targeting the PI3K-Akt pathway, either alone or in combination. These second
      generation inhibitors are essentially a specific chemical moiety that helps to
      form a strong hydrogen bond interaction with the PI3K/Akt molecule. The goal of
      this review is to delineate the current efforts that have been undertaken to
      inhibit the various components of the PI3K and Akt pathway in different types of
      cancer both in vitro and in vivo. Our focus here is on these novel therapies and
      their inhibitory effects that depend upon their chemical nature, as well as their
      development towards clinical trials.

PMID- 22983394
TI  - Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular
      coagulation (DIC).
AB  - AIM: To evaluate the effects of tanshinone IIA (Tan IIA), a lipophilic diterpene
      from the Chinese herb Salvia miltiorrhiza, on lipopolysaccharide (LPS)-induced
      disseminated intravascular coagulation (DIC) in rabbits. METHODS: LPS-induced DIC
      model was made in adult male New Zealand rabbits by continuous intravenous
      infusion of LPS (0.5 mg/kg) via marginal ear vein for 6 h. The animals were
      simultaneously administered with Tan IIA (1, 3 and 10 mg/kg) or heparin (500 000
      IU/kg) through continuous infusion via the contralateral marginal ear vein for 6
      h. Before and 2 and 6 h after the start of LPS infusion, blood samples were taken
      for biochemical analyses. RESULTS: Continuous infusion of LPS into the rabbits
      gradually impaired the hemostatic parameters, damaged renal and liver functions,
      increased the plasma TNF-alpha level, and led to a high mortality rate (80%).
      Treatment of the rabbits with Tan IIA dose-dependently attenuated the increase in
      activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin
      fibrinogen degradation products (FDP); ameliorated the decrease in plasma levels
      of fibrinogen and platelets; and reversed the decline in activity of protein C
      and antithrombin III. Meanwhile, the treatment significantly suppressed the
      increase in the plasma levels of aminotransferase, creatinine and TNF-alpha, and
      led to much lower mortality (46.7% and 26.7% for the medium- and high-dose
      groups). Treatment of the rabbits with the high dose of heparin also effectively
      improved the hemostatic parameters, ameliorated liver and renal injuries, and
      reduced the plasma level of TNF-alpha, and significantly reduced the mortality
      (33.3%). CONCLUSION: Tan IIA exerts a protective effect against DIC in rabbits.

PMID- 22983395
TI  - Endothelial PI3K-C2alpha, a class II PI3K, has an essential role in angiogenesis
      and vascular barrier function.
AB  - The class II alpha-isoform of phosphatidylinositol 3-kinase (PI3K-C2alpha) is
      localized in endosomes, the trans-Golgi network and clathrin-coated vesicles;
      however, its functional role is not well understood. Global or endothelial-cell
      specific deficiency of PI3K-C2alpha resulted in embryonic lethality caused by
      defects in sprouting angiogenesis and vascular maturation. PI3K-C2alpha knockdown
      in endothelial cells resulted in a decrease in the number of PI3-phosphate
      enriched endosomes, impaired endosomal trafficking, defective delivery of VE
      cadherin to endothelial cell junctions and defective junction assembly. PI3K
      C2alpha knockdown also impaired endothelial cell signaling, including vascular
      endothelial growth factor receptor internalization and endosomal RhoA activation.
      Together, the effects of PI3K-C2alpha knockdown led to defective endothelial cell
      migration, proliferation, tube formation and barrier integrity. Endothelial PI3K
      C2alpha deficiency in vivo suppressed postischemic and tumor angiogenesis and
      diminished vascular barrier function with a greatly augmented susceptibility to
      anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in
      response to angiotensin II infusion. Thus, PI3K-C2alpha has a crucial role in
      vascular formation and barrier integrity and represents a new therapeutic target
      for vascular disease.

PMID- 22983396
TI  - Oncogenic NRAS signaling differentially regulates survival and proliferation in
      melanoma.
AB  - The discovery of potent inhibitors of the BRAF proto-oncogene has revolutionized
      therapy for melanoma harboring mutations in BRAF, yet NRAS-mutant melanoma
      remains without an effective therapy. Because direct pharmacological inhibition
      of the RAS proto-oncogene has thus far been unsuccessful, we explored systems
      biology approaches to identify synergistic drug combination(s) that can mimic RAS
      inhibition. Here, leveraging an inducible mouse model of NRAS-mutant melanoma, we
      show that pharmacological inhibition of mitogen-activated protein kinase kinase
      (MEK) activates apoptosis but not cell-cycle arrest, which is in contrast to
      complete genetic neuroblastoma RAS homolog (NRAS) extinction, which triggers both
      of these effects. Network modeling pinpointed cyclin-dependent kinase 4 (CDK4) as
      a key driver of this differential phenotype. Accordingly, combined
      pharmacological inhibition of MEK and CDK4 in vivo led to substantial synergy in
      therapeutic efficacy. We suggest a gradient model of oncogenic NRAS signaling in
      which the output is gated, resulting in the decoupling of discrete downstream
      biological phenotypes as a result of incomplete inhibition. Such a gated
      signaling model offers a new framework to identify nonobvious coextinction
      target(s) for combined pharmacological inhibition in NRAS-mutant melanomas.

PMID- 22983397
TI  - In vivo photodynamic therapy using upconversion nanoparticles as remote
      controlled nanotransducers.
AB  - Conventional photodynamic therapy (PDT) is limited by the penetration depth of
      visible light needed for its activation. Here we used mesoporous-silica-coated
      upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert
      deeply penetrating near-infrared light to visible wavelengths and a carrier of
      photosensitizers. We also used the multicolor-emission capability of the UCNs at
      a single excitation wavelength for simultaneous activation of two
      photosensitizers for enhanced PDT. We showed a greater PDT efficacy with the dual
      photosensitizer approach compared to approaches using a single photosensitizer,
      as determined by enhanced generation of singlet oxygen and reduced cell
      viability. In vivo studies also showed tumor growth inhibition in PDT-treated
      mice by direct injection of UCNs into melanoma tumors or intravenous injection of
      UCNs conjugated with a tumor-targeting agent into tumor-bearing mice. As the
      first demonstration, to the best of our knowledge, of the photosensitizer-loaded
      UCN as an in vivo-targeted PDT agent, this finding may serve as a platform for
      future noninvasive deep-cancer therapy.

PMID- 22983398
TI  - Highly electrically conductive layered carbon derived from polydopamine and its
      functions in SnO2-based lithium ion battery anodes.
AB  - Thin carbonized polydopamine (C-PDA) coatings are found to have similar
      structures and electrical conductivities to those of multilayered graphene doped
      with heteroatoms. Greatly enhanced electrochemical properties are achieved with C
      PDA-coated SnO(2) nanoparticles where the coating functions as a mechanical
      buffer layer and conducting bridge.

PMID- 22983400
TI  - People with unhealthy lifestyle behaviours benefit from remote coaching via
      mobile technology.

PMID- 22983399
TI  - Critical review and synthesis of the epidemiologic evidence on formaldehyde
      exposure and risk of leukemia and other lymphohematopoietic malignancies.
AB  - PURPOSE: Recent epidemiologic studies indicate elevated risks for some
      lymphohematopoietic malignancies (LHM) related to formaldehyde exposure. We
      performed a systematic review of literature to assess the strength and
      consistency of associations. METHODS: We summarized published literature in the
      PubMed database of the National Library of Medicine during 1966-2012. Literature
      was categorized according to study design and population: industrial cohort
      studies, professional cohort studies, and population-based case-control studies.
      RESULTS: Findings from occupational cohort and population-based case-control
      studies were very inconsistent for LHM, including myeloid leukemia. Apart from
      some isolated exceptions, relative risks were close to the null, and there was
      little evidence for dose-response relations for any of the LHM. CONCLUSIONS: At
      present, there is no consistent or strong epidemiologic evidence that
      formaldehyde is causally related to any of the LHM. The absence of established
      toxicological mechanisms further weakens any arguments for causation. To be
      informative, future epidemiologic research should improve on formaldehyde
      exposure assessment and apply modern diagnostic schemes for specific LHM.

PMID- 22983401
TI  - Approaching the quality of antibiotic prescriptions in primary care using
      reimbursement data.
AB  - Our objectives for this investigation were: (i) to design quality measures of
      outpatient antibiotic use that could be calculated at the individual general
      practitioner (GP) level using reimbursement data only; and (ii) to analyse the
      variability in antibiotic prescriptions between GPs regarding these measures in
      south-eastern France. Based on the literature and international therapeutic
      guidelines, we designed a set of quality measures in an exploratory attempt to
      assess the quality of antibiotic prescriptions. We performed a cross-sectional
      study of antibiotic prescriptions in adults in south-eastern France in 2009,
      using data from the outpatient reimbursement database of the French National
      Health Insurance (NHI). We carried out a cluster analysis to group GPs according
      to their antibiotic prescribing behaviour. Six quality measures were calculated
      at the GP level, with wide variations in practice regarding all these measures. A
      six-cluster solution was identified, with one cluster grouping 56 % of the sample
      and made up of GPs having the most homogeneous pattern of prescription for all
      six quality measures, probably reflecting better antibiotic prescribing. Total
      pharmaceutical expenses (per patient), penicillin combinations use, quinolone use
      and seasonal variation of quinolone use were all positively associated with a
      more heterogeneous and possibly less appropriate use of antibiotics in a
      multivariate analysis. These quality measures could be useful to assess GPs'
      antibiotic prescribing behaviour in countries where no information system
      provides easy access to data linking drug use to a clinical condition.

PMID- 22983404
TI  - Apparatus for in situ monitoring of copper in coastal waters.
AB  - Apparatus is designed and tested to determine metals in situ in seawater.
      Voltammetry with a vibrating gold microwire electrode (VGME) is combined with a
      battery powered potentiostat and a processor board and is tested for in situ
      monitoring of copper (Cu) in coastal waters. The VGME was combined with solid
      state reference and counter electrodes to make a single vibrating probe which was
      rated up to a depth of 40 m. The measuring mode for Cu was square-wave anodic
      stripping voltammetry whilst dissolved oxygen (DO) was monitored by a linear
      sweep scan in a negative potential direction. The working electrode was
      reactivated between measurements using a suitable potential sequence. The
      novelties of this work are the field-testing of apparatus incorporating a VGME
      for copper monitoring, which eliminates the need for pumping and reagents, but
      has sufficient sensitivity for low ambient levels of copper, and the use of a
      novel potential sequence to stabilise the response over a long time period. The
      apparatus has a measuring time of about 6 weeks and a measuring frequency of 12
      h(-1). Measurement is reagent-free and power use is low as no pump is required.
      Experiments are carried out to test the stability of response of the system at
      various temperatures and its robustness with respect to long-term copper
      monitoring. Preliminary data were obtained during autonomous deployment over
      several weeks on a buoy in the Irish Sea. Vertical movement of the buoy caused
      individual measurements to have a variability of about 15%. It was found that
      longer term variability of the electrode could be minimised by normalisation of
      the Cu response over that of DO as the response was related to diffusion through
      the electrode surface which was similarly affected. The detected fraction of Cu
      (labile Cu) amounted to 1.5-4 nM during different deployments at a total Cu
      concentration of ~10 nM. The same ratio was found by voltammetry in samples taken
      to the laboratory. The new apparatus has demonstrated that metals in coastal
      waters can be monitored at trace level, much facilitating the monitoring of
      outfalls and local water contamination. Because of its sensitivity the apparatus
      would be of use in estuarine as well as coastal waters, with the aim of
      monitoring intermittent variability in the copper concentration.

PMID- 22983402
TI  - Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with
      liver disease among patients coinfected with human immunodeficiency virus and
      hepatitis C virus.
AB  - Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially
      related to liver diseases. The aim of the study was to quantify TTV and TTMV in
      human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to
      study the relationship between the TTV and TTMV viral loads and the severity of
      liver disease. We carried out a cross-sectional study in 245 patients coinfected
      with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group),
      and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV
      and TTMV by quantitative real-time polymerase chain reaction (PCR). The
      prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group
      were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and
      TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 %
      (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p <= 0.05).
      HIV/HCV-coinfected patients with HIV viral load >=50 copies/mL and patients with
      severe activity grade had the highest viral loads of TTV and TTMV (p <= 0.05).
      HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/MUL) had
      increased odds of having advanced fibrosis or severe necroinflammatory activity
      grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV
      load (>1.88 log copies/MUL) had decreased odds of having no/minimal fibrosis and
      no/mild activity grade, and increased odds of having a high fibrosis progression
      rate. In conclusion, TTV and TTMV might play a role in the development of liver
      disease in immunodeficiency patients, such as the patients coinfected with HIV
      and HCV.

PMID- 22983405
TI  - Asymmetric synthesis of a structurally and stereochemically complex spirooxindole
      pyran scaffold through an organocatalytic multicomponent cascade reaction.
AB  - A novel and convenient organocatalytic tandem reaction has been developed for the
      asymmetric assembly of saturated aldehydes (or enals), nitroolefins and isatins
      to produce six-membered oxa-spirooxindole backbones bearing four contiguous
      stereogenic centers and multiple functional groups with high stereoselectivity.

PMID- 22983406
TI  - Recent progress of n-type organic semiconducting small molecules for organic
      field-effect transistors.
AB  - Substantial improvement of n-channel organic semiconductors has been realized
      after the research focus turned from hole transporting (p-type) organic
      semiconductors to electron-transporting (n-type) and ambipolar-transporting
      organic semiconductors. In this review, several novel n-type semiconducting small
      molecules, as well as promising developments of traditional systems, which were
      reported to exhibit high electron-transport performance in the last three years
      will be summarized.

PMID- 22983407
TI  - Randomized trial of partial vs. stepwise caries removal: 3-year follow-up.
AB  - This randomized, multicenter clinical trial evaluated the effectiveness of 2
      treatments for deep caries lesions - partial caries removal (PCR) and stepwise
      excavation (SW) - with respect to the primary outcome of pulp vitality for a 3
      year follow-up period. Inclusion criteria were as follows: patients with
      permanent molars presenting deep caries lesions (lesion affecting >= 1/2 of the
      dentin on radiographic examination), positive response to a cold test, absence of
      spontaneous pain, negative sensitivity to percussion, and absence of periapical
      lesions (radiographic examination). Teeth randomly assigned to PCR (test)
      received incomplete caries removal and filling in a single session. Outcome
      success was evaluated by assessment of pulp vitality, determined by pulp
      sensitivity to a cold test and the absence of periapical lesions. Data were
      analyzed by a Weibull regression model with shared frailty term (survival
      analysis). At baseline, 299 treatments were executed: PCR, 152 and SW, 147. By
      the end of the 3-year follow-up period, 213 teeth had been evaluated. Adjusted
      survival rates were 91% for PCR and 69% for SW (p = 0.004). These results suggest
      that there is no need to re-open a cavity and perform a second excavation for
      pulp vitality to be preserved (Clinical trials registration NCT00887952).

PMID- 22983408
TI  - Effectiveness of maternal counseling in reducing caries in Cree children.
AB  - This cluster-randomized pragmatic (effectiveness) trial tested maternal
      counseling based on Motivational Interviewing (MI) as an approach to control
      caries in indigenous children. Nine Cree communities in Quebec, Canada were
      randomly allocated to test or control. MI-style counseling was delivered in test
      communities to mothers during pregnancy and at well-baby visits. Data on outcomes
      were collected when children were 30 months old. Two hundred seventy-two mothers
      were recruited from the 5 test and 4 control communities. Baseline
      characteristics were comparable but not equivalent for both groups. At trial's
      end, 241 children had follow-up. The primary analysis outcome was enamel caries
      with substance loss (d2); no statistically significant treatment effect was
      detected. Prevalence of treated and untreated caries at the d2 level was 76% in
      controls vs. 65% in test (p = 0.17). Exploratory analyses suggested a substantial
      preventive effect for untreated decay at or beyond the level of the dentin, d3
      (prevalences: 60% controls vs. 35% test), and a particularly large treatment
      effect when mothers had 4 or more MI-style sessions. Overall, these results
      provide preliminary evidence that, for these young, indigenous children, an MI
      style intervention has an impact on severity of caries (clinical trial
      registration ISRCTN41467632).

PMID- 22983409
TI  - Effect of a calcium-silicate-based restorative cement on pulp repair.
AB  - In cases of pulp injury, capping materials are used to enhance tertiary dentin
      formation; Ca(OH)(2) and MTA are the current gold standards. The aim of this
      study was to evaluate the capacity of a new calcium-silicate-based restorative
      cement to induce pulp healing in a rat pulp injury model. For that purpose,
      cavities with mechanical pulp exposure were prepared on maxillary first molars of
      27 six-week-old male rats, and damaged pulps were capped with either the new
      calcium-silicate-based restorative cement (Biodentine), MTA, or Ca(OH)(2).
      Cavities were sealed with glass-ionomer cement, and the repair process was
      assessed at several time-points. At day 7, our results showed that both the
      evaluated cement and MTA induced cell proliferation and formation of
      mineralization foci, which were strongly positive for osteopontin. At longer time
      points, we observed the formation of a homogeneous dentin bridge at the injury
      site, secreted by cells displaying an odontoblastic phenotype. In contrast, the
      reparative tissue induced by Ca(OH)(2) showed porous organization, suggesting a
      reparative process different from those induced by calcium silicate cements.
      Analysis of these data suggests that the evaluated cement can be used for direct
      pulp-capping.

PMID- 22983410
TI  - Construct validity of Locker's global oral health item.
AB  - With clinical oral examinations not always possible in health surveys,
      researchers may instead be invited to add questions to a wider health survey. In
      such situations, an item is needed which adequately represents both clinical and
      self-reported oral health. This study investigated the clinical validity of
      Locker's global self-reported oral health item among young middle-aged adults in
      populations in New Zealand and Australia. Clinical examination and self-report
      data (including the OHIP-14) were obtained from recent national dental surveys in
      NZ and Australia, and from age-38 assessments in the Dunedin Multidisciplinary
      Health and Development Study. National dataset analyses involved 35- to 44-year
      olds. Caries and tooth-loss experience showed mostly consistent, statistically
      significant gradients across the Locker item responses; those responding
      'Excellent' had the lowest scores, and those responding 'Poor' the highest.
      Periodontitis experience gradients in the NZ national sample were mainly as
      hypothesized; those rating their oral health as 'Poor' had the highest disease
      experience. OHIP-14 gradients across the Locker item responses were consistent
      and as hypothesized. The proportion of disease in the population borne by those
      'Fair' or 'Poor' ranged from 26% to 72%. These findings provide preliminary
      support for the measure's validity as a global self-reported oral health measure
      in young middle-aged adults.

PMID- 22983411
TI  - The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis.
AB  - Uncoupled bone resorption leads to net alveolar bone loss in periodontitis. The
      deficiency of LL-37, the only human antimicrobial peptide in the cathelicidin
      family, in patients with aggressive periodontitis suggests that LL-37 may play a
      pivotal role in the inhibition of alveolar bone destruction in periodontitis. We
      aimed to investigate a novel function of LL-37 in osteoimmunity by blocking
      osteoclastogenesis in vitro. Human osteoclast progenitor cells were isolated from
      a buffy coat of blood samples. The cells were cultured in the presence of various
      concentrations of LL-37 during an in vitro induction of osteoclastogenesis. Non
      toxic doses of LL-37 could block multinuclear formation of the progenitor cells
      and significantly diminish the number of tartrate-resistant acid-phosphatase
      positive cells and the formation of resorption pits (p < 0.05), whereas these
      concentrations induced cellular proliferation, as demonstrated by increased
      expression of proliferating cell nuclear antigen. Expression of several
      osteoclast genes was down-regulated by LL-37 treatment. It was demonstrated that
      nuclear translocation of nuclear-factor-activated T-cells 2 (NFAT2) was blocked
      by LL-37 treatment, consistent with a significant reduction in the calcineurin
      activity (p < 0.005). Collectively, our findings demonstrate that LL-37 inhibits
      the in vitro osteoclastogenesis by inhibiting the calcineurin activity, thus
      preventing nuclear translocation of NFAT2.

PMID- 22983414
TI  - Pneumocystis jiroveci pneumonia revealing de novo mutation causing X-linked hyper
      IgM syndrome in an infant male. The first case reported from French Guiana.
AB  - BACKGROUND: The X-linked hyper-IgM (XHIM) syndrome is a rare form of primary
      immunodeficiency disorder characterized by hypogammaglobulinemia and impaired
      cell immunity. OBSERVATION: We report history of Guianese family affected by XHIM
      syndrome. The eldest boy died at 7 months from pneumonia. The 5-month-old
      youngest boy presented with a potentially fatal episode of Pneumocystis jiroveci
      pneumonia. The diagnosis was done in the Pediatric Unit of Immunohematology of
      Hopital Necker in Paris. CONCLUSIONS: This report points to the importance of
      diagnosis of XHIM to allow early treatment to minimize serious infections and to
      detect carriers in XHIM families for genetic counseling.

PMID- 22983413
TI  - Neurogenic stunned myocardium after embolization in two children with vein of
      Galen aneurysmal malformation.
AB  - INTRODUCTION: This study reports the first cases of neurogenic stunned myocardium
      in two children with vein of Galen aneurysmal malformation after interventional
      treatment. PATIENTS: Two newborns with vein of Galen aneurysmal malformation and
      high output cardiac failure developed a severe reversible left ventricular
      dysfunction shortly after embolization, concurrently with acute hydrocephalus.
      RESULTS: There was a resolution of the cardiac symptoms of left ventricular
      dysfunction within a few days under treatment with milrinone and dobutamine.
      CONCLUSIONS: Reversible left ventricular dysfunction is observed in adult
      patients mainly after subarachnoid hemorrhage and is called neurogenic stunned
      myocardium (NSM). Other forms of brain injuries have also been identified
      accounting for this condition in adults. In pediatric population especially with
      specific cerebral diseases, NSM may be underdiagnosed.

PMID- 22983415
TI  - Significance of interleukin-6 (IL-6) and C-reactive protein (CRP) in children and
      young adults with febrile neutropenia during chemotherapy for cancer: a
      prospective study.
AB  - OBJECTIVES: We evaluated the usefulness of interleukin-6 (IL-6) and C-reactive
      protein (CRP) at the onset of febrile neutropenia and 72 hours later, in
      identifying risk groups and assessing response to antibiotic therapy. METHODS:
      All episodes of febrile neutropenia were divided in 3 study groups
      microbiologically documented infection (MDI), clinically documented infection
      (CDI), and fever of unknown origin (FUO). Three outcome groups were defined as
      those responding to first-line antibiotics (R1), those responding to second-line
      antibiotics (R2), and those requiring antifungal therapy (RAF). Median values of
      IL-6 and CRP were compared between the groups. RESULTS: There were 57 episodes of
      febrile neutropenia among 26 patients younger than 25 years during 1 year of
      study period. On day 1, median IL-6 level was significantly lower in FUO group
      compared with CDI+MDI groups combined (P < 0.001). Rise in CRP on day 3 was
      highly significant to differentiate MDI group from other 2 groups (P < 0.001).
      The CRP also increased significantly on day 3 in RAF (P < 0.001) and R2 (P =
      0.002) groups than in R1 group. CONCLUSIONS: Low level of IL-6 may help
      differentiate patients with FUO from those with documented infections. A rising
      CRP is indicative of serious infection.

PMID- 22983416
TI  - Molecular analysis and clinical findings of Griscelli syndrome patients.
AB  - Griscelli syndrome (GS) is a rare autosomal recessive disorder associated with
      skin or hair hypopigmentation, hepatosplenomegaly, pancytopenia, and immunologic
      and central nervous system abnormalities. GS type II is caused by RAB27A
      mutations. We present RAB27A mutation analysis of 6 cases diagnosed as GS type
      II. Missense mutations (L26P and L130P) in 2 cases, deletion of 5 bases
      (514delCAAGC) in 2 cases, and 1 base deletion (148delA) in 2 cases were detected.
      This report has importance in phenotype-genotype correlation of different types
      of mutations including missense mutations and deletions within the RAB27A gene in
      GSII syndrome.

PMID- 22983417
TI  - Views of childhood cancer survivors and their families on the provision and
      format of a treatment summary.
AB  - INTRODUCTION: Summaries of diagnosis, treatments, and their potential late
      adverse health effects (treatment summaries) are increasingly being provided
      routinely to survivors of childhood cancer. There is relatively little research
      into opinions of service users on the provision and format of treatment
      summaries. METHODS: Semistructured interviews were conducted with 24 survivors of
      childhood cancer, and 25 parents of 20 of these survivors (n=49) were asked to
      explore these issues. Survivors were aged 4 to 22 years, with a range of previous
      oncological diagnoses. The mean (range) interval since treatment completion was
      4.5 (0.5 to 13) years. RESULTS: Twelve survivors (50%) and 16 parents (64%) fully
      supported the use of treatment summaries as: a memory aid, a reference tool for
      planned and emergency medical situations, life and financial planning, and to
      promote ownership of health. Four survivors felt they did not want, or did not
      need, a reminder of their medical past. Most participants (63% of survivors)
      desired a verbal explanation plus a written A4 paper treatment summary. However,
      other formats (wallet sized, audio guides) were suggested to address practical
      and individual needs raised by participants. CONCLUSIONS: Most service users
      would benefit from treatment summaries, although notably not all. The format and
      timing of the provision need to be carefully considered.

PMID- 22983418
TI  - Prognostic factors and survival patterns in pediatric low-grade gliomas over 4
      decades.
AB  - BACKGROUND: This study reports changes in long-term survival after the
      introduction of modern imaging in pediatric patients with low-grade gliomas
      (LGGs). METHODS: Records from 351 consecutive pediatric patients diagnosed with
      LGG between 1970 and 2009 at Mayo Clinic Rochester were reviewed and divided into
      diagnosis before (group I: 1970 to 1989) and after (group II: 1990 to 2009)
      postoperative magnetic resonance imaging became regularly used in pediatric LGG.
      RESULTS: Median progression-free survival (PFS) and overall survival (OS) were
      not reached. Overall, 10-year PFS was 62% and OS was 90%. On multivariate
      analysis, improved PFS was associated with gross total resection (GTR; P<0.0001)
      and postoperative radiation therapy (RT; P<0.0001). In those undergoing less than
      GTR, PFS was improved with RT, nearing rates of patients receiving GTR (P=0.12).
      On multivariate analysis, higher OS was associated with GTR (P<0.0001) and
      pilocytic histology (P=0.03). Group II had fewer headaches, fewer sensory/motor
      symptoms, less postoperative RT, and more GTRs. OS and PFS were not different
      between the groups. CONCLUSIONS: This large series of pediatric LGG patients with
      long-term follow-up found no significant changes in OS or PFS over time. Overall,
      GTR was associated with improved OS and PFS. RT was associated with an
      improvement in PFS, with the greatest benefit seen in patients undergoing less
      than GTR.

PMID- 22983419
TI  - Hydroxyurea treatment can avoid the need for aggressive surgery in pediatric
      fibromatosis.
AB  - Aggressive fibromatosis is a rare tumor of borderline malignancy with a marked
      local aggressiveness. Surgery is the mainstay of treatment but complete tumor
      resection is often not easy to achieve without functional and cosmetic sequelae.
      We report a case of a pretreated child with aggressive fibromatosis who responded
      to hydroxyurea, avoiding the need for demolitive surgery.

PMID- 22983420
TI  - Acute megakaryoblastic leukemia with increased hematogones in children.
AB  - We describe 2 patients, a 4-month-old male and a 17-month-old female, with de
      novo acute megakaryoblastic leukemia with increased number of hematogones at
      diagnosis. Both children were admitted in the hospital with thrombocytopenia. The
      bone marrow smears in the first child revealed the presence of 60% cells with
      morphologic features consistent with acute megakaryoblastic leukemia. In the
      other, the initial bone marrow aspirate was dry tap but on the following aspirate
      10% cells with lymphoblastic morphology could be seen. The bone marrow flow
      cytometry showed the presence of hematogones-38% in the first case and 20% in the
      second-with absence of blasts. Repeated bone marrow aspirates, trephines, and
      immunophenotypic as well as molecular studies, confirmed the diagnosis of M7.
      Both children were treated according to the Berlin-Frankfurt-Munster 2004
      protocol.

PMID- 22983421
TI  - Creating a standardized process to offer the standard of care: continuous process
      improvement methodology is associated with increased rates of sperm
      cryopreservation among adolescent and young adult males with cancer.
AB  - BACKGROUND: There is limited literature on strategies to overcome the barriers to
      sperm banking among adolescent and young adult (AYA) males with cancer. By
      standardizing our process for offering sperm banking to AYA males before cancer
      treatment, we aimed to improve rates of sperm banking at our institution.
      MATERIALS AND METHODS: Continuous process improvement is a technique that has
      recently been applied to improve health care delivery. We used continuous process
      improvement methodologies to create a standard process for fertility preservation
      for AYA males with cancer at our institution. We compared rates of sperm banking
      before and after standardization. RESULTS: In the 12-month period after
      implementation of a standardized process, 90% of patients were offered sperm
      banking. We demonstrated an 8-fold increase in the proportion of AYA males' sperm
      banking, and a 5-fold increase in the rate of sperm banking at our institution.
      DISCUSSION: Implementation of a standardized process for sperm banking for AYA
      males with cancer was associated with increased rates of sperm banking at our
      institution. This study supports the role of standardized health care in
      decreasing barriers to sperm banking.

PMID- 22983422
TI  - Are exposure-based cognitive behavioral therapies safe during pregnancy?
AB  - Anxiety disorders during pregnancy are highly prevalent and associated with
      serious and enduring consequences for both mother and child. Exposure-based
      cognitive behavioral (CBT) and behavioral therapies (BT) represent the most
      empirically supported psychosocial treatments for anxiety disorders in general
      adult samples. Pregnant women, however, generally have been excluded from this
      body of research. Evidence that pregnant women inhabit a unique biological
      context combined with untested assumptions that exposure would unduly stress or
      harm the fetus have likely prohibited inquiry. This paper seeks to remedy this
      gap by integrating findings from obstetric, psychiatric, and psychological
      research to inform central questions regarding exposure-based treatment of
      anxiety disorders during pregnancy. Based on available evidence, we consider the
      potential risks and benefits of CBT/BT for anxiety disorders during pregnancy
      relative to other currently available treatment options. From a multidisciplinary
      research perspective, we argue that exposure-based therapies are likely to be
      safe during pregnancy, particularly relative to the alternatives. However, we
      also highlight critical questions for future research to directly test the
      biopsychological impact of exposure-based therapies among pregnant women.

PMID- 22983423
TI  - FGF23 production by osteocytes.
AB  - Fibroblast growth factor 23 (FGF23), a known regulator of phosphate homeostasis,
      is produced by cells residing in bone, namely, osteocytes, to target a distant
      organ, the kidney. Elevated FGF23 levels have recently been found systemically
      and in osteocytes in patients and animal models of chronic kidney disease.
      Associations between serum FGF23 level and vascular dysfunction, vascular
      calcification, and increased risk of cardiovascular disease have also been
      observed. In this review we discuss FGF23 expression in osteocytes and the
      potential means to regulate expression and function of this protein at the
      osteocyte level.

PMID- 22983425
TI  - Determination of the thermal and physical properties of black tattoo ink using
      compound analysis.
AB  - Despite the widespread use of laser therapy in the removal of tattoos,
      comparatively little is known about its mechanism of action. There is a need for
      an improved understanding of the composition and thermal properties of the tattoo
      ink in order that simulations of laser therapy may be better informed and
      treatment parameters optimised. Scanning electron microscopy and time-of-flight
      secondary ion mass spectrometry identified that the relative proportions of the
      constituent compounds of the ink likely to exist in vivo are the following:
      carbon black pigment (89 %), carvacrol (5 %), eugenol (2 %), hexenol (3 %) and
      propylene glycol (1 %). Chemical compound property tables identify that changes
      in phase of these compounds lead to a considerable reduction in the density and
      thermal conductivity of the ink and an increase in its specific heat as
      temperature increases. These temperature-dependent values of density, thermal
      conductivity and specific heat are substantially different to the constant
      values, derived from water or graphite at a fixed temperature, which have been
      applied in the simulations of laser therapy as previously described in the
      literature. Accordingly, the thermal properties of black tattoo ink described in
      this study provide valuable information that may be used to improve simulations
      of tattoo laser therapy. 

PMID- 22983424
TI  - Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical
      and intravitreal applications.
AB  - The next-generation ophthalmic anti-VEGF therapeutics must aim at being superior
      to the currently available agents with regard to potency and improved drug
      delivery, while still being stable and safe to use at elevated concentrations. We
      show here the generation of a set of highly potent VEGF-A antagonistic DARPins
      (designed ankyrin repeat proteins) delivering these properties. DARPins with
      single-digit picomolar affinity to human VEGF-A were generated using ribosome
      display selections. Specific and potent human VEGF-A binding was confirmed by
      ELISA and endothelial cell sprouting assays. Cross-reactivity with VEGF-A of
      several species was confirmed by ELISA. Intravitreally injected DARPin penetrated
      into the retina and reduced fluorescein extravasation in a rabbit model of
      vascular leakage. In addition, topical DARPin application was found to diminish
      corneal neovascularization in a rabbit suture model, and to suppress laser
      induced neovascularization in a rat model. Even at elevated doses, DARPins were
      safe to use. The fact that several DARPins are highly active in various assays
      illustrates the favorable class behavior of the selected binders. Anti-VEGF-A
      DARPins thus represent a novel class of highly potent and specific drug
      candidates for the treatment of neovascular eye diseases in both the posterior
      and the anterior eye chamber.

PMID- 22983426
TI  - Letter regarding "Clinical and histologic effects from CO2 laser treatment of
      keloids".

PMID- 22983429
TI  - Progress in neuro-otology research in the last year.
AB  - Herein, we summarize articles in the field of neuro-otology published in the
      Journal of Neurology over the last year. Topics included acute and chronic
      vertigo as well as auditory and ocular motor disorders. Characteristic lesion
      locations in Pusher syndrome are reported and the usefulness of bedside ocular
      motor tests in vertebrobasilar stroke is revisited. Probing the vestibular system
      and its value in predicting the outcome in vegetative state is discussed. Several
      articles address new diagnostic and therapeutic approaches in different disorders
      associated with chronic vestibular, auditory or gait deficits. In a series of
      case reports, we focus on different eye movement disorders in the vertical plane,
      which are often difficult to assess.

PMID- 22983427
TI  - Paraneoplastic and non-paraneoplastic autoimmunity to neurons in the central
      nervous system.
AB  - Autoimmune central nervous system (CNS) inflammation occurs both in a
      paraneoplastic and non-paraneoplastic context. In a widening spectrum of clinical
      disorders, the underlying adaptive (auto) immune response targets neurons with a
      divergent role for cellular and humoral disease mechanisms: (1) in encephalitis
      associated with antibodies to intracellular neuronal antigens, neuronal antigen
      specific CD8(+) T cells seemingly account for irreversible progressive neuronal
      cell death and neurological decline with poor response to immunotherapy. However,
      a pathogenic effect of humoral immune mechanisms is also debated. (2) In
      encephalitis associated with antibodies to synaptic and extrasynaptic neuronal
      cell surface antigens, potentially reversible antibody-mediated disturbance of
      synaptic transmission and neuronal excitability occurs in the absence of
      excessive neuronal damage and accounts for a good response to immunotherapy.
      However, a pathogenic effect of cellular immune mechanisms is also debated. We
      provide an overview of entities, clinical hallmarks, imaging features,
      characteristic laboratory, electrophysiological, cerebrospinal fluid and
      neuropathological findings, cellular and molecular disease mechanisms as well as
      therapeutic options in these two broad categories of inflammatory CNS disorders.

PMID- 22983428
TI  - Role of intestinal peptides and the autonomic nervous system in postprandial
      hypotension in patients with multiple system atrophy.
AB  - Postprandial hypotension (PPH) is a major clinical problem in patients with
      autonomic failure such as that observed in multiple system atrophy (MSA). The
      pathophysiology of PPH remains unclear, although autonomic dysfunction and
      gastrointestinal vasoactive peptides have been suspected to participate in its
      pathogenesis. We measured blood pressure and plasma levels of glucose, insulin,
      noradrenaline, neurotensin, glucagon-like peptide (GLP)-1 and GLP-2 before and
      after meal ingestion in 24 patients with MSA to reveal the roles of the autonomic
      nervous system and gastrointestinal vasoactive peptides in PPH. We performed a
      second meal-ingestion test by administering acarbose to evaluate the effects of
      acarbose (an alpha-glucosidase inhibitor) on PPH and vasoactive peptides in 14
      patients with MSA and PPH. We also evaluated blood pressure responses to the head
      up tilt test and heart rate variability in all the patients. Severities of PPH
      and orthostatic hypotension were significantly correlated. Patients with PPH had
      significantly worse orthostatic hypotension and lower heart rate variability than
      those without PPH. Postprandial GLP-1 secretion was higher in patients with PPH
      than in those without PPH. No significant differences were observed in the
      postprandial increases in plasma levels of glucose, insulin, noradrenaline,
      neurotensin or GLP-2. Acarbose significantly attenuated postprandial hypotension
      and tended to decrease GLP-2 secretion. Our results indicate that autonomic
      failure is involved in the pathogenesis of PPH and confirm that acarbose has a
      preventive effect against PPH in patients with MSA. Decreased postprandial
      secretion of GLP-2, which increases intestinal blood pooling, may attenuate PPH
      in patients with MSA.

PMID- 22983430
TI  - Au(III)-promoted polyaniline gold nanospheres with electrocatalytic recycling of
      self-produced reactants for signal amplification.
AB  - A novel and redox-active nanocatalyst, Au(III)-promoted polyaniline gold
      nanosphere (GPANG), was designed as the nanolabel for highly efficient
      electrochemical immunoassay of human IgG by coupling with electrocatalytic
      recycling of self-produced reactants.

PMID- 22983431
TI  - A ferroelectric memristor.
AB  - Memristors are continuously tunable resistors that emulate biological synapses.
      Conceptualized in the 1970s, they traditionally operate by voltage-induced
      displacements of matter, although the details of the mechanism remain under
      debate. Purely electronic memristors based on well-established physical phenomena
      with albeit modest resistance changes have also emerged. Here we demonstrate that
      voltage-controlled domain configurations in ferroelectric tunnel barriers yield
      memristive behaviour with resistance variations exceeding two orders of magnitude
      and a 10 ns operation speed. Using models of ferroelectric-domain nucleation and
      growth, we explain the quasi-continuous resistance variations and derive a simple
      analytical expression for the memristive effect. Our results suggest new
      opportunities for ferroelectrics as the hardware basis of future neuromorphic
      computational architectures.

PMID- 22983432
TI  - Heterogeneous nucleation of organic crystals mediated by single-molecule
      templates.
AB  - Fundamental understanding of how crystals of organic molecules nucleate on a
      surface remains limited because of the difficulty of probing rare events at the
      molecular scale. Here we show that single-molecule templates on the surface of
      carbon nanohorns can nucleate the crystallization of two organic compounds from a
      supersaturated solution by mediating the formation of disordered and mobile
      molecular nanoclusters on the templates. Single-molecule real-time transmission
      electron microscopy indicates that each nanocluster consists of a maximum of
      approximately 15 molecules, that there are fewer nanoclusters than crystals in
      solution, and that in the absence of templates physisorption, but not crystal
      formation, occurs. Our findings suggest that template-induced heterogeneous
      nucleation mechanistically resembles two-step homogeneous nucleation.

PMID- 22983433
TI  - Cancer-testis antigen expression and immunogenicity in AL amyloidosis.
AB  - Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to
      multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7
      (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In
      this study, we investigated the expression and immunogenicity of several CTAs in
      patients with AL amyloidosis in a total of 38 bone marrow specimens by employing
      standard immunohistochemistry techniques on paraffin-embedded archival tissues.
      Plasma samples from 35 patients (27 with matched bone marrow samples) were also
      analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7
      was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38
      AL amyloid cases. The expression pattern was mostly focal. There were no
      significant differences with regard to organ involvement, response to treatment,
      or prognosis in CTA positive compared to negative cases. None of the specimens
      showed spontaneous humoral immunity to CT7, but sero reactivity was observed in
      individual patients to other CTAs. This study identifies CT7 as the prevalent CTA
      in plasma cells of patients with AL amyloidosis. Further analyses determining the
      biology of CTAs in AL amyloidosis and their value as potential targets for
      immunotherapy are warranted.

PMID- 22983434
TI  - Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete
      for the HSC niche?
AB  - In the adult mammal, normal haematopoiesis occurs predominantly in the bone
      marrow, where primitive haematopoietic stem cells (HSC) and their progeny reside
      in specialised microenvironments. The bone marrow microenvironment contains
      specific anatomical areas (termed niches) that are highly specialised for the
      development of certain blood cell types, for example HSCs. The HSC niche provides
      important cell-cell interactions and signalling molecules that regulate HSC self
      renewal and differentiation processes. These same signals and interactions are
      also important in the progression of haematological malignancies, such as
      multiple myeloma (MM). This review provides an overview of the bone marrow
      microenvironment and its involvement in normal, physiological HSC maintenance and
      plasma cell growth throughout MM disease progression.

PMID- 22983435
TI  - Deficits in transcriptional regulators of cortical parvalbumin neurons in
      schizophrenia.
AB  - OBJECTIVE: In schizophrenia, alterations within the prefrontal cortical GABA
      system appear to be most prominent in neurons that contain parvalbumin or
      somatostatin but not calretinin. The transcription factors Lhx6 and Sox6 play
      critical roles in the specification, migration, and maturation of parvalbumin and
      somatostatin neurons, but not calretinin neurons, and continue to be strongly
      expressed in this cell type-specific manner in the prefrontal cortex of adult
      humans. The authors investigated whether Lhx6 and/or Sox6 mRNA levels are
      deficient in schizophrenia, which may contribute to cell type-specific
      disturbances in cortical parvalbumin and somatostatin neurons. METHOD: The
      authors used quantitative PCR and in situ hybridization with film and grain
      counting analyses to quantify mRNA levels in postmortem samples of prefrontal
      cortex area 9 of 42 schizophrenia subjects and 42 comparison subjects who had no
      psychiatric diagnoses in life, as well as antipsychotic-exposed monkeys. RESULTS:
      In schizophrenia subjects, the authors observed lower mRNA levels for Lhx6,
      parvalbumin, somatostatin, and glutamate decarboxylase (GAD67; the principal
      enzyme in GABA synthesis), but not Sox6 or calretinin. Cluster analysis revealed
      that a subset of schizophrenia subjects consistently showed the most severe
      deficits in the affected transcripts. Grain counting analyses revealed that some
      neurons that normally express Lhx6 were not detectable in schizophrenia subjects.
      Finally, lower Lhx6 mRNA levels were not attributable to psychotropic medications
      or illness chronicity. CONCLUSIONS: These data suggest that in a subset of
      individuals with schizophrenia, Lhx6 deficits may contribute to a failure of some
      cortical parvalbumin and somatostatin neurons to successfully migrate or develop
      a detectable GABA-ergic phenotype.

PMID- 22983437
TI  - Sterically demanding imidazolinium salts through the activation and cyclization
      of formamides.
AB  - A new protocol was developed for the synthesis of sterically demanding
      imidazolinium salts. This procedure was adopted for the synthesis of seven NHC
      salts, including ones that were demonstrated to be inaccessible using the
      conventional orthoformate ester type cyclization method.

PMID- 22983436
TI  - Capture, isolation and release of cancer cells with aptamer-functionalized glass
      bead array.
AB  - Early detection and isolation of circulating tumor cells (CTC) can enable better
      prognosis for cancer patients. A Hele-Shaw device with aptamer functionalized
      glass beads is designed, modeled, and fabricated to efficiently isolate cancer
      cells from a cellular mixture. The glass beads are functionalized with anti
      epidermal growth factor receptor (EGFR) aptamer and sit in ordered array of pits
      in polydimethylsiloxane (PDMS) channel. A PDMS encapsulation is then used to
      cover the channel and to flow through cell solution. The beads capture cancer
      cells from flowing solution depicting high selectivity. The cell-bound glass
      beads are then re-suspended from the device surface followed by the release of
      92% cells from glass beads using combination of soft shaking and anti-sense RNA.
      This approach ensures that the cells remain in native state and undisturbed
      during capture, isolation and elution for post-analysis. The use of highly
      selective anti-EGFR aptamer with the glass beads in an array and subsequent
      release of cells with antisense molecules provide multiple levels of binding and
      release opportunities that can help in defining new classes of CTC enumeration
      devices.

PMID- 22983438
TI  - Corneal microprojections in coleoid cephalopods.
AB  - The cornea is the first optical element in the path of light entering the eye,
      playing a role in image formation and protection. Corneas of vertebrate simple
      camera-type eyes possess microprojections on the outer surface in the form of
      microridges, microvilli, and microplicae. Corneas of invertebrates, which have
      simple or compound eyes, or both, may be featureless or may possess
      microprojections in the form of nipples. It was previously unknown whether
      cephalopods (invertebrates with camera-type eyes like vertebrates) possess
      corneal microprojections and, if so, of what form. Using scanning electron
      microscopy, we examined corneas of a range of cephalopods and discovered nipple
      like microprojections in all species. In some species, nipples were like those
      described on arthropod compound eyes, with a regular hexagonal arrangement and
      sizes ranging from 75 to 103 nm in diameter. In others, nipples were nodule
      shaped and irregularly distributed. Although terrestrial invertebrate nipples
      create an antireflective surface that may play a role in camouflage, no such
      optical function can be assigned to cephalopod nipples due to refractive index
      similarities of corneas and water. Their function may be to increase surface-area
      to-volume ratio of corneal epithelial cells to increase nutrient, gas, and
      metabolite exchange, and/or stabilize the corneal mucous layer, as proposed for
      corneal microprojections of vertebrates.

PMID- 22983439
TI  - Visual flight control in naturalistic and artificial environments.
AB  - Although the visual flight control strategies of flying insects have evolved to
      cope with the complexity of the natural world, studies investigating this
      behaviour have typically been performed indoors using simplified two-dimensional
      artificial visual stimuli. How well do the results from these studies reflect the
      natural behaviour of flying insects considering the radical differences in
      contrast, spatial composition, colour and dimensionality between these visual
      environments? Here, we aim to answer this question by investigating the effect of
      three- and two-dimensional naturalistic and artificial scenes on bumblebee flight
      control in an outdoor setting and compare the results with those of similar
      experiments performed in an indoor setting. In particular, we focus on
      investigating the effect of axial (front-to-back) visual motion cues on ground
      speed and centring behaviour. Our results suggest that, in general, ground speed
      control and centring behaviour in bumblebees is not affected by whether the
      visual scene is two- or three dimensional, naturalistic or artificial, or whether
      the experiment is conducted indoors or outdoors. The only effect that we observe
      between naturalistic and artificial scenes on flight control is that when the
      visual scene is three-dimensional and the visual information on the floor is
      minimised, bumblebees fly further from the midline of the tunnel. The findings
      presented here have implications not only for understanding the mechanisms of
      visual flight control in bumblebees, but also for the results of past and future
      investigations into visually guided flight control in other insects.

PMID- 22983440
TI  - Low circulating IGF-I bioactivity is associated with human longevity: findings in
      centenarians' offspring.
AB  - Centenarians' offspring represent a suitable model to study age-dependent
      variables (e.g. IGF-I) potentially involved in the modulation of the lifespan.
      The aim of the present study was to investigate the role of the IGF-I in human
      longevity. We evaluated circulating IGF-I bioactivity measured by an innovative
      IGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, total IGF
      II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians' offspring and 80
      offspring-controls of which both parents died relatively young. Both groups were
      well-matched for age, gender and BMI with the centenarians' offspring. IGF-I
      bioactivity (p<0.01), total IGF-I (p<0.01) and the IGF-I/IGFBP-3 molar ratio
      (p<0.001) were significantly lower in centenarians' offspring compared to
      offspring matched-controls. Serum insulin, glucose, HOMA2-B% and HOMA2-S% values
      were similar between both groups. In centenarians' offspring IGF-I bioactivity
      was inversely associated to insulin sensitivity. IN CONCLUSION: 1) centenarians'
      offspring had relatively lower circulating IGF-I bioactivity compared to
      offspring matched-controls; 2) IGF-I bioactivity in centenarians' offspring was
      inversely related to insulin sensitivity. These data support a role of the IGF
      I/insulin system in the modulation of human aging process.

PMID- 22983441
TI  - Glaucoma progression associated with Leber's hereditary optic neuropathy.
AB  - The purpose of this article is to describe a case of open-angle glaucoma
      progression associated with Leber's hereditary optic neuropathy. Single case
      analysis method is used. A 53-year-old woman with a previous diagnosis of
      glaucoma presented with progressive visual field loss. Complete ophthalmological
      examination and blood tests were negative for other concomitant diseases. Genetic
      counseling revealed mitochondrial DNA mutation compatible with the diagnosis of
      Leber's hereditary optic neuropathy. In conclusion, the case describes the
      concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We
      hypothesize that the two diseases may have a cumulative effect on oxidative
      stress and retinal ganglion cell death with the consequent rapid progression of
      visual impairment. Screening for mitochondrial DNA mutations may be requested in
      patients with glaucoma who, despite pharmacologically controlled intraocular
      pressure, show rapid progression of the disease.

PMID- 22983442
TI  - Cytokine activation induces human memory-like NK cells.
AB  - Natural killer (NK) cells are lymphocytes that play an important role in the
      immune response to infection and malignancy. Recent studies in mice have shown
      that stimulation of NK cells with cytokines or in the context of a viral
      infection results in memory-like properties. We hypothesized that human NK cells
      exhibit such memory-like properties with an enhanced recall response after
      cytokine preactivation. In the present study, we show that human NK cells
      preactivated briefly with cytokine combinations including IL-12, IL-15, and IL-18
      followed by a 7- to 21-day rest have enhanced IFN-gamma production after
      restimulation with IL-12 + IL-15, IL-12 + IL-18, or K562 leukemia cells. This
      memory-like phenotype was retained in proliferating NK cells. In CD56(dim) NK
      cells, the memory-like IFN-gamma response was correlated with the expression of
      CD94, NKG2A, NKG2C, and CD69 and a lack of CD57 and KIR. Therefore, human NK
      cells have functional memory-like properties after cytokine activation, which
      provides a novel rationale for integrating preactivation with combinations of IL
      12, IL-15, and IL-18 into NK cell immunotherapy strategies.

PMID- 22983443
TI  - ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation
      by AML1-ETO in acute myeloid leukemia.
AB  - ERG and FLI1 are closely related members of the ETS family of transcription
      factors and have been identified as essential factors for the function and
      maintenance of normal hematopoietic stem cells. Here genome-wide analysis
      revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO in
      t(8;21) AMLs and identified ERG/FLI1 as proteins that facilitate binding of
      oncofusion protein complexes. In addition, we demonstrate that ERG and FLI1 bind
      the RUNX1 promoter and that shRNA-mediated silencing of ERG leads to reduced
      expression of RUNX1 and AML1-ETO, consistent with a role of ERG in
      transcriptional activation of these proteins. Finally, we identify H3 acetylation
      as the epigenetic mark preferentially associated with ETS factor binding. This
      intimate connection between ERG/FLI1 binding and H3 acetylation implies that one
      of the molecular strategies of oncofusion proteins, such as AML1-ETO and PML-RAR
      alpha, involves the targeting of histone deacetylase activities to ERG/FLI1 bound
      hematopoietic regulatory sites. Together, these results highlight the dual
      importance of ETS factors in t(8;21) leukemogenesis, both as transcriptional
      regulators of the oncofusion protein itself as well as proteins that facilitate
      AML1-ETO binding.

PMID- 22983444
TI  - Loss of kindlin-3 alters the threshold for NK cell activation in human leukocyte
      adhesion deficiency-III.
AB  - Recent evidence suggests that kindlin-3 is a major coactivator, required for
      most, if not all, integrin activities. Here we studied the function of kindlin-3
      in regulating NK cell activation by studying a patient with kindlin-3 deficiency
      (leukocyte adhesion deficiency-III). We found that kindlin-3 is required for NK
      cell migration and adhesion under shear force. Surprisingly, we also found that
      kindlin-3 lowers the threshold for NK cell activation. Loss of kindlin-3 has a
      pronounced effect on NK cell-mediated cytotoxicity triggered by single activating
      receptors. In contrast, for activation through multiple receptors, kindlin-3
      deficiency is overcome and target cells killed. The realization that NK cell
      activity is impaired, but not absent in leukocyte adhesion deficiency, may lead
      to the development of more efficient therapy for this rare disease.

PMID- 22983445
TI  - Protein kinase D-HDAC5 signaling regulates erythropoiesis and contributes to
      erythropoietin cross-talk with GATA1.
AB  - In red cell development, the differentiation program directed by the
      transcriptional regulator GATA1 requires signaling by the cytokine
      erythropoietin, but the mechanistic basis for this signaling requirement has
      remained unknown. Here we show that erythropoietin regulates GATA1 through
      protein kinase D activation, promoting histone deacetylase 5 (HDAC5) dissociation
      from GATA1, and subsequent GATA1 acetylation. Mice deficient for HDAC5 show
      resistance to anemic challenge and altered marrow responsiveness to
      erythropoietin injections. In ex vivo studies, HDAC5(-/-) progenitors display
      enhanced entry into and passage through the erythroid lineage, as well as
      evidence of erythropoietin-independent differentiation. These results reveal a
      molecular pathway that contributes to cytokine regulation of hematopoietic
      differentiation and offer a potential mechanism for fine tuning of lineage
      restricted transcription factors by lineage-specific cytokines.

PMID- 22983446
TI  - ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial
      ischemia/reperfusion injury in mice.
AB  - Epidemiologic studies suggest that elevated VWF levels and reduced ADAMTS13
      activity in the plasma are risk factors for myocardial infarction. However, it
      remains unknown whether the ADAMTS13-VWF axis plays a causal role in the
      pathophysiology of myocardial infarction. In the present study, we tested the
      hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial
      ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration,
      and myocyte apoptosis in the left ventricular area were quantified after 30
      minutes of ischemia and 23.5 hours of reperfusion injury. Adamts13(-/-) mice
      exhibited significantly larger infarcts concordant with increased neutrophil
      infiltration and myocyte apoptosis compared with wild-type (WT) mice. In
      contrast, Vwf(-/-) mice exhibited significantly reduced infarct size, neutrophil
      infiltration, and myocyte apoptosis compared with WT mice, suggesting a
      detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13(-/-)
      mice with neutralizing Abs to VWF significantly reduced infarct size compared
      with control Ig-treated mice. Finally, myocardial I/R injury in Adamts13(-/
      )/Vwf(-/-) mice was similar to that in Vwf(-/-) mice, suggesting that the
      exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency
      is VWF dependent. These findings reveal that ADAMTS13 and VWF are causally
      involved in myocardial I/R injury.

PMID- 22983448
TI  - The ikyoku system of university orthopedic surgery departments: an in-hospital
      organizational system unique to Japan--its significance for advancement of basic
      medical science related to orthopedic surgery.

PMID- 22983447
TI  - Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells.
AB  - miRs play a critical role in tumor pathogenesis as either oncogenes or tumor
      suppressor genes. However, the role of miRs and their regulation in response to
      proteasome inhibitors in multiple myeloma (MM) is unclear. In the current study,
      miR profiling in proteasome inhibitor MLN2238-treated MM.1S MM cells shows up
      regulation of miR33b. Mechanistic studies indicate that the induction of miR33b
      is predominantly via transcriptional regulation. Examination of miR33b in patient
      MM cells showed a constitutively low expression. Overexpression of miR33b
      decreased MM cell viability, migration, colony formation, and increased apoptosis
      and sensitivity of MM cells to MLN2238 treatment. In addition, overexpression of
      miR33b or MLN2238 exposure negatively regulated oncogene PIM-1 and blocked PIM-1
      wild-type, but not PIM-1 mutant, luciferase activity. Moreover, PIM-1
      overexpression led to significant abrogation of miR33b- or MLN2238-induced cell
      death. SGI-1776, a biochemical inhibitor of PIM-1, triggered apoptosis in MM.
      Finally, overexpression of miR33b inhibited tumor growth and prolonged survival
      in both subcutaneous and disseminated human MM xenograft models. Our results show
      that miR33b is a tumor suppressor that plays a role during MLN2238-induced
      apoptotic signaling in MM cells, and these data provide the basis for novel
      therapeutic strategies targeting miR33b in MM.

PMID- 22983449
TI  - [Traumatic abruption of the placenta with disseminated intravascular
      coagulation].
AB  - Trauma in pregnancy is infrequent and a systematic primary strategy constitutes a
      real challenge for the interdisciplinary team. With a high fetal mortality rate
      and a substantial maternal mortality rate traumatic placental abruption is a
      severe emergency which every anesthetist should be aware of. After hemodynamic
      stabilization of the mother and control of the viability of the fetus the therapy
      of traumatic placental abruption consists mostly of an immediate caesarean
      section. Coagulopathy by depletion of coagulation factors as well as disseminated
      intravascular coagulation (DIC) have to be expected and consequently a massive
      blood loss must be anticipated. Thrombelastography provides assistance for fast
      differential diagnosis and goal-directed treatment of the disturbed sections of
      the coagulation cascade.

PMID- 22983451
TI  - [Evidence in palliative medicine : on the way to therapy recommendations in
      palliative medicine].

PMID- 22983450
TI  - [Treatment of nausea and vomiting with 5HT3 receptor antagonists, steroids,
      antihistamines, anticholinergics, somatostatinantagonists, benzodiazepines and
      cannabinoids in palliative care patients : a systematic review].
AB  - BACKGROUND: Various recommendations exist for the treatment of nausea and
      vomiting in palliative care but only few studies and even less systematic reviews
      look into antiemetic therapy for patients receiving palliative care. OBJECTIVES:
      This systematic review aims to analyze the current evidence for antiemetic
      treatment with 5HT3 receptor antagonists, steroids, antihistamines,
      anticholinergics, somatostatin analogs, benzodiazepines and cannabinoids in
      palliative care patients with far advanced cancer not receiving chemotherapy or
      radiotherapy, acquired immune deficiency syndrome (AIDS), chronic obstructive
      pulmonary disease (COPD), progressive heart failure, amyotrophic lateral
      sclerosis (ALS) or multiple sclerosis (MS). Results regarding evidence of
      treatment with prokinetic and neuroleptic agents will be published separately.
      METHODS: The electronic databases PubMed and EmBase were systematically searched
      for studies (published 1966-2011) dealing with antiemetic therapy in palliative
      care and electronic retrieval was completed by manual searching. Studies with
      patients undergoing chemotherapy or radiotherapy, pediatric studies and studies
      published in languages other than English or German were excluded. Studies
      addressing therapy with 5HT3 receptor antagonists, steroids, antihistamines,
      anticholinergics, somatostatin analogs, benzodiazepines or cannabinoids were
      identified and selected for this systematic review. RESULTS: In the general
      search 75 relevant studies were found. Of those 36 addressed 5HT3 receptor
      antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs,
      benzodiazepines and cannabinoids, 13 considered 5HT3 receptor antagonists, 10
      somatostatin antagonists, 9 steroids, 5 cannabinoids, 4 anticholinergics, 1
      antihistamines and none benzodiazepines. Furthermore six systematic reviews
      exist. Evidence for any drug used as an antiemetic is low. Concerning 5HT3
      receptor antagonists data are insufficient for recommendations on the treatment
      of patients with AIDS and MS due to the small size of included patient groups.
      For patients with cancer contradictory results were published: the larger studies
      showed a positive effect of 5HT3 receptor antagonists and better efficacy, as
      compared to metoclopramide, dexamethasone and neuroleptics. Heterogeneous results
      were found for steroids, with a positive trend for patients with cancer. Data are
      insufficient for antihistamines. Studies prove effectiveness of
      butylscopolammonium in the treatment of nausea and vomiting caused by malignant
      gastrointestinal obstruction, whereas octreotide is superior to
      butylscopolammonium. Regarding benzodiazepines for symptom control of nausea and
      vomiting in palliative care patients no studies were detected. Cannabinoids were
      found to relieve nausea and vomiting in patients with cancer and AIDS but with
      notable side effects. Furthermore, the studies compared cannabinoids to less
      recent antiemetic drugs but not, for example to 5HT3 receptor antagonists.
      Regarding symptom control of nausea and vomiting in patients with COPD,
      progressive heart failure and ALS no studies were undertaken in patients
      receiving palliative care. CONCLUSIONS: In palliative care patients with nausea
      and vomiting 5HT3 receptor antagonists can be used if treatment with other
      antiemetics, such as metoclopramide and neuroleptics is not sufficient. There is
      a trend that steroids in combination with other antiemetics improve symptom
      relief. Cannabinoids rather have a status as a second line antiemetic. In cases
      of nausea and vomiting caused by malignant gastrointestinal obstruction
      octreotide showed the best and butylscopolammonium bromide the second best
      results. Concerning antihistamines and benzodiazepines insufficient data was
      found. Recommendations in the literature are mainly based on studies in patients
      with cancer. The overall strength of evidence is low. More well designed studies
      in palliative care patients are needed in order to provide evidence-based
      therapy. The English full text version of this article will be available in
      SpringerLink as of November 2012 (under "Supplemental").

PMID- 22983452
TI  - Imbalance of circulating endothelial cells and progenitors in idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Fibrogenesis during idiopathic pulmonary fibrosis (IPF) is strongly
      associated with abnormal vascular remodeling. Respective abundance of circulating
      endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the
      balance between vascular injury and repair and potentially serve as biomarkers of
      the disease. OBJECTIVES AND METHODS: We postulated that CEC and EPC subtypes
      might be differently modulated in IPF. Sixty-four consecutive patients with newly
      diagnosed IPF were prospectively enrolled and compared to thirteen healthy
      volunteers. CEC were counted with immunomagnetic CD146-coated beads; progenitors
      CD34+45(dim)/CD34+133+/CD34+KDR+were assessed through flow cytometry and EPC
      (colony-forming-units-Endothelial Cells, CFU-EC, and endothelial colonies forming
      cells, ECFC) were quantified by cell culture assays. RESULTS: IPF patients were
      characterized by a marked increase in CEC associated to an EPC defect: both
      CD34(+)KDR(+) cells and CFU-EC were decreased versus controls. Moreover, in IPF
      subjects with a low diffusing capacity of the lung for carbon monoxide (DL(CO)) <
      40 %, CFU-EC and ECFC were higher compared to those with DL(CO) > 40 %. Finally,
      ECFC were negatively correlated with DL(CO). During an 18 month follow up, CEC
      levels increased in patients with exacerbation, including those who died during
      follow up. Finally, ECFC from patients with exacerbation proliferative potential
      was strongly increased. CONCLUSION: IPF is basically associated with both a
      vascular injury and a repair defect. This study highlights an adaptative process
      of EPC mobilization in the most severe forms of IPF, that could reflect enhanced
      homing to the pulmonary vasculature, which clinical consequences remain to be
      determined.

PMID- 22983453
TI  - Prevalence of viral infections in Norwegian cats with and without feline lower
      urinary tract disease.
AB  - The prevalence of various viral infections was examined in primary accession
      cases of feline lower urinary tract disease (FLUTD) and healthy control cats in
      Norway. Urine samples from 102 cats with clinical signs of FLUTD and 73 healthy
      control cats were tested for the presence of feline calicivirus (FCV), feline
      coronavirus (FCoV) and feline herpesvirus-1 (FHV-1) by polymerase chain reaction.
      All urinary samples were negative for FCV and FCoV. One (1%) of the FLUTD cats
      was found to be positive for FHV-1. The results did not indicate an association
      between the viral infections examined and signs of FLUTD in the study sample.

PMID- 22983454
TI  - Xenotransfusion with canine blood in the feline species: review of the
      literature.
AB  - Xenotransfusion (the transfusion of blood from another species) of canine blood
      to cats has been historically performed commonly and is still performed nowadays
      in some countries. Considering the current lack of commercial availability of
      haemoglobin-based oxygen carrier solution (Oxyglobin), there may be rare
      occasions when treating an anaemic cat when compatible feline blood cannot be
      obtained, and where a transfusion with canine blood may need to be considered as
      a life-saving procedure. This article reviews the published evidence about feline
      xenotransfusion with canine blood and the results that can be expected with this
      procedure. Published evidence in a limited number of cases (62 cats) indicates
      that cats do not appear to have naturally-occurring antibodies against canine red
      blood cell antigens: compatibility tests prior to the first transfusion did not
      demonstrate any evidence of agglutination or haemolysis of canine red cells in
      feline serum or plasma. No severe acute adverse reactions have been reported in
      cats receiving a single transfusion with canine whole blood. Anaemic cats
      receiving canine blood are reported to improve clinically within hours. However,
      antibodies against canine red blood cells are produced rapidly and can be
      detected within 4-7 days of the transfusion, leading to the destruction of the
      transfused canine red cells in a delayed haemolytic reaction. The average
      lifespan of the transfused canine red cells is less than 4 days. Any repeated
      transfusion with canine blood later than 4-6 days after the first transfusion
      causes anaphylaxis, which is frequently fatal.

PMID- 22983455
TI  - Omentum-preserving gastrectomy for advanced gastric cancer: a propensity-matched
      retrospective cohort study.
AB  - BACKGROUND AND OBJECTIVES: We clarified the impact of omentectomy for advanced
      gastric cancer on patient survival from the surgical results of a high-volume
      center in Japan. METHODS: Patients who received curative gastrectomy were divided
      into two groups based on whether they underwent omentectomy. The propensity score
      matching method was used to assemble a well-balanced cohort, and relapse-free
      survival and the pattern of recurrence were compared. RESULTS: For this study,
      330 patients who fulfilled the inclusion criteria participated and were divided
      into two groups: group R, patients who received omentectomy, and group P,
      patients who received omentum-preserving gastrectomy. After performing score
      matching, 196 patients were selected. The 3- and 5-year relapse-free survival
      rates were 72.9% (95% confidence interval, 64.1-81.7) and 66.2% (56.6-75.8%) in
      group R, and 76.7% (67.9-81.2) and 67.3% (55.1-79.5) in group P, which were not
      significantly different (P = 0.750). Regarding sites of relapses, no differences
      were observed between the groups (P = 0.863). CONCLUSIONS: In this series,
      omentum-preserving gastrectomy for advanced gastric cancer did not increase the
      peritoneal relapse rate or affect patient survival compared to conventional
      gastrectomy. The non-inferiority of the omission of omentectomy should be
      evaluated by a randomized controlled trial.

PMID- 22983456
TI  - A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam
      for acute childhood seizures.
AB  - The objective of this study is to compare the safety and efficacy of midazolam
      given intranasally with diazepam given intravenously in the treatment of acute
      childhood seizures. A randomized controlled study was conducted in a pediatric
      emergency department in a tertiary general hospital. Fifty children aged from 1
      month to 12 years presenting with acute seizures of at least 10 min duration were
      enrolled during a 12 month period. Intranasal midazolam (0.2 mg/kg) and
      intravenous diazepam (0.3 mg/kg) were administered. The main outcome measures
      were interval between arrival at hospital and starting treatment and interval
      between arrival at hospital and cessation of seizures. Intranasal midazolam and
      intravenous diazepam were equally effective. Overall 18 of 27 seizures were
      controlled with midazolam and 15 of 23 with diazepam. The mean interval between
      arrival at hospital and starting treatment was significantly shorter in the
      midazolam group [3.37 min (SD 2.46)] as compared to the diazepam group [14.13 min
      (SD 3.39)]. The mean interval between cessation of seizures and arrival at
      hospital was significantly shorter in the midazolam group [6.67 min (SD 3.12)] as
      compared to the diazepam group [17.18 min (SD 5.09)]. The mean interval between
      control of seizures and administration of the drug was shorter in the diazepam
      group [2.67 min (SD 2.31)] as compared to the midazolam group [3.01 min (SD
      2.79)]. No significant side effects were observed in either group. Seizures were
      controlled more quickly with intravenous diazepam than with intranasal midazolam.
      Midazolam was as safe and effective as diazepam. The overall interval between
      arrival at hospital and cessation of seizures was shorter with intranasal
      midazolam than with intravenous diazepam. The intranasal route can be possibly
      used not only in medical centres, but with appropriate instruction by the parents
      of children with acute seizures at home.

PMID- 22983457
TI  - TGFalpha shedding assay: an accurate and versatile method for detecting GPCR
      activation.
AB  - A single-format method to detect multiple G protein-coupled receptor (GPCR)
      signaling, especially Galpha(12/13) signaling, presently has limited throughput
      and sensitivity. Here we report a transforming growth factor-alpha (TGFalpha)
      shedding assay, in which GPCR activation is measured as ectodomain shedding of a
      membrane-bound proform of alkaline phosphatase-tagged TGFalpha (AP-TGFalpha) and
      its release into conditioned medium. AP-TGFalpha shedding response occurred
      almost exclusively downstream of Galpha(12/13) and Galpha(q) signaling. Relying
      on chimeric Galpha proteins and promiscuous Galpha(16) protein, which can couple
      with Galpha(s)- and Galpha(i)-coupled GPCRs and induce Galpha(q) signaling, we
      used the TGFalpha shedding assay to detect 104 GPCRs among 116 human GPCRs. We
      identified three orphan GPCRs (P2Y10, A630033H20 and GPR174) as Galpha(12/13)
      coupled lysophosphatidylserine receptors. Thus, the TGFalpha shedding assay is
      useful for studies of poorly characterized Galpha(12/13)-coupled GPCRs and is a
      versatile platform for detecting GPCR activation including searching for ligands
      of orphan GPCRs.

PMID- 22983458
TI  - Reversible labeling of native and fusion-protein motifs.
AB  - The reversible covalent attachment of chemical probes to proteins has long been
      sought as a means to visualize and manipulate proteins. Here we demonstrate the
      full reversibility of post-translational custom pantetheine modification of
      Escherichia coli acyl carrier protein for visualization and functional studies.
      We use this iterative enzymatic methodology in vitro to reversibly label acyl
      carrier protein variants and apply these tools to NMR structural studies of
      protein-substrate interactions.

PMID- 22983460
TI  - Re: Re: The efficacy and safety of ureteroscopy for ureteral calculi in
      pregnancy: our experience in 32 patients.

PMID- 22983462
TI  - Addressing stigma to strengthen psychiatric education.

PMID- 22983461
TI  - The technical details of treatment of kidney stone in children.

PMID- 22983463
TI  - The unspoken tyranny of regulatory agencies: a commentary on the ACGME Resident
      Survey.

PMID- 22983464
TI  - Opportunities to enhance prevention-related competencies in graduate medical
      education in psychiatry: a position statement of the Prevention Committee of the
      Group for the Advancement of Psychiatry.

PMID- 22983465
TI  - Professionalism and the internet in psychiatry: what to teach and how to teach
      it.

PMID- 22983466
TI  - Clinical skills verification in general psychiatry: recommendations of the ABPN
      Task Force on Rater Training.
AB  - OBJECTIVE: The American Board of Psychiatry and Neurology (ABPN) announced in
      2007 that general psychiatry training programs must conduct clinical skills
      verification (CSV), consisting of observed clinical interviews and case
      presentations during residency, as one requirement to establish graduates'
      eligibility to sit for the written certification examination. To facilitate
      implementation of these requirements, the ABPN convened a task force to prepare
      training materials for faculty and programs to guide them in the CSV process.
      This article reviews the specific requirements for the CSV experience within
      general residency programs, and briefly describes the recommendations of the task
      force for faculty training and program implementation. METHODS: Materials
      prepared by the ABPN Task Force include background information on the intent of
      the observed interview, a literature review on assessment methods, aids to train
      faculty in direct observation of clinical work, directions for effective
      feedback, notes regarding special issues for cross-cultural trainees,
      clarification of performance standards, and recommendations for structuring and
      conducting the assessments. RESULTS: Recommendations of the task force include
      the use of a variety of clinical settings for CSV assessments, flexibility in the
      duration of CSV interviews, use of formative and summative feedback after each
      CSV assessment, and frequent use of the CSV across all years of training. Formal
      faculty training is recommended to help establish performance parameters,
      increase interrater reliability, and improve the quality of feedback.
      CONCLUSIONS: The implementation of the CSV process provides psychiatry training
      programs with an excellent opportunity to assess how interviewing skills are
      taught and evaluated. In the process, psychiatry educators have an opportunity to
      establish performance parameters that will guide the training of residents in
      patient interaction and evaluation.

PMID- 22983467
TI  - Trends in psychotherapy training: a national survey of psychiatry residency
      training.
AB  - OBJECTIVE: The authors sought to determine current trends in residency training
      of psychiatrists. METHOD: The authors surveyed U.S. general-psychiatry training
      directors about the amount of didactic training, supervised clinical experience,
      and numbers of patients treated in the RRC-mandated models of psychotherapy
      (psychodynamic, cognitive-behavioral therapy [CBT], and supportive). Questions
      regarding other models of psychotherapy and about challenges in training were
      also included. RESULTS: The results demonstrate a wide range of experiences in
      psychotherapy education. Psychodynamic training is the most robust, but has the
      greatest variability. CBT training has advanced significantly over the past
      decade. Supportive psychotherapy is the most widely practiced, but receives the
      least amount of didactic time and supervision. CONCLUSION: The authors discuss
      next steps in the evolution of psychotherapy education for psychiatrists.

PMID- 22983468
TI  - Patients' appraisal of psychiatric trainee interview skills.
AB  - OBJECTIVE: The aim of this pilot project was to explore the extent to which
      judgments made by psychiatrist examiners accord with those of patients in
      postgraduate clinical examinations, so as to inform further consideration of the
      role of patients in such assessments. METHOD: Senior psychiatrist examiners (N=8)
      and patients (N=30) rated 16 aspects of trainee psychiatrist interviewing style
      and performance during 30 observed clinical interviews (OCIs) conducted in the
      format of official examinations. RESULTS: Significant differences were apparent
      in the judgments of examiners and patients regarding 7 of 16 rated aspects of
      trainee performance. Differences were evident largely in domains in which
      patients could be expected to be "expert," reflecting their subjective experience
      of the interviewer. By contrast, there was little difference in the judgments of
      patients and examiners on the more technical criteria. CONCLUSION: These
      preliminary findings provide some challenge to the assumption that psychiatrists
      are the best judges of the "technical" skills and knowledge required by the
      profession. They support previous findings, with simulated patients, of the
      discrepancy between patient and examiner judgments of the more subjective
      elements of the examination. Psychiatric patients could contribute to clinical
      examinations as co-examiners, rather than merely constituting the substrate for
      the examination.

PMID- 22983469
TI  - Psychiatry in the Harvard Medical School-Cambridge Integrated Clerkship: an
      innovative, year-long program.
AB  - OBJECTIVE: The authors present what is to their knowledge the first description
      of a model for longitudinal third-year medical student psychiatry education.
      METHOD: A longitudinal, integrated psychiatric curriculum was developed,
      implemented, and sustained within the Harvard Medical School-Cambridge Integrated
      Clerkship. Curriculum elements include longitudinal mentoring by attending
      physicians in an outpatient psychiatry clinic, exposure to the major
      psychotherapies, psychopharmacology training, acute psychiatry "immersion"
      experiences, and a variety of clinical and didactic teaching sessions. RESULTS:
      The longitudinal psychiatry curriculum has been sustained for 8 years to-date,
      providing effective learning as demonstrated by OSCE scores, NBME shelf exam
      scores, written work, and observed clinical work. The percentage of students in
      this clerkship choosing psychiatry as a residency specialty is significantly
      greater than those in traditional clerkships at Harvard Medical School and
      greater than the U.S. average. CONCLUSION: Longitudinal integrated clerkship
      experiences are effective and sustainable; they offer particular strengths and
      opportunities for psychiatry education, and may influence student choice of
      specialty.

PMID- 22983470
TI  - Emotional intelligence and selection to administrative chief residency.
AB  - OBJECTIVE: The authors sought to determine whether emotional intelligence, as
      measured by the BarOn emotional quotient inventory (EQ-i), is associated with
      selection to administrative chief resident. METHOD: Authors invited senior-year
      residents at the University of Texas Health Science Center at Houston to
      participate in an observational cross-sectional study using the BarOn EQ-i. In
      October 2009 they sent an invitation e-mail to 66 senior residents, with a
      reminder e-mail 1 month later. The study was designed to detect a 15-point
      difference in EQ-i scores with 80% power. RESULTS: Of the 66 invited residents,
      69.6% participated in the study. Average total EQ-I score was 104.9. Among senior
      year residents, there were no statistically significant differences in EQ-i
      scores between administrative chief residents (at 109) and non-administrative
      chief residents (at 103.2). CONCLUSION: Administrative chief residents do not
      demonstrate higher Emotional Intelligence, as measured by the EQ-i, than other
      senior-year residents.

PMID- 22983471
TI  - Associate residency training directors in psychiatry: demographics, professional
      activities, and job satisfaction.
AB  - OBJECTIVE: The purpose of this study was to characterize associate training
      director (ATD) positions in psychiatry. METHOD: An on-line survey was e-mailed in
      2009 to all ATDs identified through the American Association of Directors of
      Psychiatric Residency Training (AADPRT). Survey questions elicited information
      regarding demographics, professional activities, job satisfaction, and goals.
      RESULTS: Of 170 ATDs surveyed, 73 (42.9%) completed the survey. Most respondents
      (71.3%) had been in their positions for 3 years or less. Many ATDs indicated that
      they were involved in virtually all aspects of residency training; 75% of
      respondents agreed that they were happy with their experience. However, specific
      concerns included inadequate time and compensation for the ATD role in addition
      to a lack of mentorship and unclear job expectations. CONCLUSIONS: Thoughtful
      attention to the construction of the ATD role may improve job satisfaction.

PMID- 22983472
TI  - Do they stay or do they go? Residents who become faculty at their training
      institutions.
AB  - OBJECTIVE: Few data exist on the topic of internal hiring of trainees in academic
      medicine. This study examines nationally representative data to determine the
      frequency of faculty psychiatrists who are employed in the same department in
      which they completed their residency training. METHOD: Estimates of internal
      faculty hiring were obtained by reviewing a random sample of publically available
      psychiatry department websites in the United States. RESULTS: Among the 26
      departments reviewed, there was wide variation in the rates of psychiatrists who
      received training in the same department in which they were currently employed as
      faculty members, with a median of 45.5%, ranging from 0% to 71%. CONCLUSION:
      Results suggest that departmental hiring of one's own graduates is common
      practice in academic psychiatry, and there is wide variation in this practice
      across psychiatry departments in the United States.

PMID- 22983473
TI  - Virtual patients as novel teaching tools in psychiatry.

PMID- 22983474
TI  - Exploring benefits of audience-response systems on learning: a review of the
      literature.

PMID- 22983475
TI  - A comprehensive national telemental health training program.

PMID- 22983476
TI  - Evaluation of a collaborative mental health program in residency training.

PMID- 22983477
TI  - Psychiatry resident/fellow-initiated and -designed multi-modal psychopharmacology
      curriculum for major depression.

PMID- 22983478
TI  - Revitalization of research education in psychiatry: implications for training
      during residency.

PMID- 22983479
TI  - Why I like being an academic psychiatrist.

PMID- 22983480
TI  - Highly sensitive microscale in vivo sensor enabled by electrophoretic assembly of
      nanoparticles for multiple biomarker detection.
AB  - This paper describes a microscale in vivo sensor platform device for the
      simultaneous detection of multiple biomarkers. We designed the polymer-based
      biosensors incorporating multiple active isolated areas, as small as 70 MUm * 70
      MUm, for antigen detection. The fabrication approach involved conventional micro-
      and nano-fabrication processes followed by site-specific electrophoretic directed
      assembly of antibody-functionalized nanoparticles. To ensure precise and large
      scale manufacturing of these biosensors, we developed a semi-automated system for
      the attachment of the 250-MUm biosensor to a 300-MUm catheter probe. Our
      fabrication and post-processing procedures should enable large-scale production
      of such biosensor devices at lower manufacturing cost. The principle of detection
      with these biosensors involved a simple fluorescence-based enzyme-linked
      immunosorbent assay. These biosensors exhibit high selectivity (ability to
      selectively detect multiple biomarkers of different diseases), specificity
      (ability to target generic to specific disease biomarkers), rapid antigen uptake,
      and low detection limits (for carcinoembryonic antigen, 31.25 pg mL(-1); for
      nucleosomes, 62.5 pg mL(-1)), laying the foundation for potential early detection
      of various diseases.

PMID- 22983481
TI  - Development of an intervention for foster parents of young foster children with
      externalizing behavior: theoretical basis and program description.
AB  - Foster parents are often faced with serious externalizing behaviors of their
      foster child. These behavioral problems may induce family stress and are related
      to less effective parenting and often increase. Foster children with behavioral
      problems are also more at risk of placement breakdown. An intervention to support
      foster parents of young foster children with externalizing behaviors is necessary
      to improve the effectiveness of foster placements. Based on research on effective
      parenting interventions and special needs of foster children, a treatment
      protocol was developed. This paper describes theoretical foundations for the
      content and form of the intervention and gives an overview of the modular
      treatment protocol. Preliminary outcomes of this intervention as well as
      challenges and future developments and research activities are discussed.

PMID- 22983482
TI  - Involving parents in indicated early intervention for childhood PTSD following
      accidental injury.
AB  - Accidental injuries represent the most common type of traumatic event to which a
      youth is likely to be exposed. While the majority of youth who experience an
      accidental injury will recover spontaneously, a significant proportion will go on
      to develop Post-Traumatic Stress Disorder (PTSD). And yet, there is little
      published treatment outcome research in this area. This review focuses on two key
      issues within the child PTSD literature--namely the role of parents in treatment
      and the timing of intervention. The issue of parental involvement in the
      treatment of child PTSD is a question that is increasingly being recognized as
      important. In addition, the need to find a balance between providing early
      intervention to at risk youth while avoiding providing treatment to those youth
      who will recover spontaneously has yet to be addressed. This paper outlines the
      rationale for and the development of a trauma-focused CBT protocol with separate
      parent and child programs, for use with children and adolescents experiencing
      PTSD following an accidental injury. The protocol is embedded within an indicated
      intervention framework, allowing for the early identification of youth at risk
      within a medical setting. Two case studies are presented in order to illustrate
      key issues raised in the review, implementation of the interventions, and the
      challenges involved.

PMID- 22983483
TI  - Complementary roles of mitochondrial respiration and ROS signaling on cellular
      aging and longevity.
AB  - Although it is widely accepted that mitochondria play fundamental roles in the
      mechanisms of cellular and organismal aging and lifespan extension, some open
      questions remain concerning the requirements for aerobic energy production and
      the effect of the potentially hazardous reactive oxygen species (ROS) byproducts
      as well as their interplay with nutrition and caloric intake.

PMID- 22983485
TI  - Hibernation patterns of Turkish hamsters: influence of sex and ambient
      temperature.
AB  - Turkish hamsters (Mesocricetus brandti) are a model organism for studies of
      hibernation, yet a detailed account of their torpor characteristics has not been
      undertaken. This study employed continuous telemetric monitoring of body
      temperature (T(b)) in hibernating male and female Turkish hamsters at ambient
      temperatures (T(a)s) of 5 and 13  degrees C to precisely characterize torpor bout
      depth, duration, and frequency, as well as rates of entry into and arousal from
      torpor. Hamsters generated brief intervals of short (<12 h), shallow test bouts
      (T(b) > 20  degrees C), followed by deep torpor bouts lasting 4-6 days at T(a) =
      5  degrees C and 2-3 days at T(a) = 13  degrees C. Females at T(a) = 5  degrees C
      had longer bouts than males, but maintained higher torpor T(b); there were no sex
      differences at T(a) = 13  degrees C. Neither body mass loss nor food intake
      differed between the two T(a)s. Hamsters entered torpor primarily during the
      scotophase (subjective night), but timing of arousals was highly variable.
      Hamsters at both T (a)s generated short, shallow torpor bouts between deep bouts,
      suggesting that this species may be capable of both hibernation and daily torpor.

PMID- 22983484
TI  - 12/15-lipoxygenase during the regulation of inflammation, immunity, and self
      tolerance.
AB  - 12/15-Lipoxygenase (12/15-LO) catalyzes the oxidation of free and esterified
      fatty acids thereby generating a whole spectrum of bioactive lipid mediators.
      This enzyme is involved in the regulation of various homeostatic processes as
      well as in the pathogenesis of multiple diseases. During the innate and adaptive
      immune response, 12/15-LO and its products exert both pro- and anti-inflammatory
      effects. Likewise, this enzyme has been implicated in the pathogenesis of
      autoimmune disease as well as in the maintenance of self-tolerance. This review
      will summarize our current knowledge about the role of 12/15-LO and will try to
      examine the two faces of this enzyme within the context of inflammation and
      immunity.

PMID- 22983486
TI  - Optimized imaging techniques for testicular masses: fast and with high accuracy.
AB  - OBJECTIVE: The purpose of this study is to determine the effectiveness of the
      diffusion-weighted magnetic resonance imaging (DWI) of the differentiation of
      benign and malignant testicular masses. METHODS: Fifteen male patients who
      admitted to our clinic with the diagnosis of testicular mass detected by
      ultrasound were enrolled to this study. The patients were between 20 and 61 years
      old (mean 25.7). Apparent diffusion coefficient (ADC) values were measured from
      ADC maps of lesion and normal testicular tissue. In addition, mean signal
      intensity (SI) measurements were obtained by using b: 1,000 of normal testicular
      tissue and lesion with three regions of interest (ROI). SI ratio values are
      obtained by dividing the value lesion SI to the normal testicular parenchyma SI.
      Histopathology of orchiectomy materials and ADC values and lesion SI rates were
      compared statistically. RESULTS: There were no significant correlation (p = 0.97)
      between ADC values of benign and malign lesions and histopathological diagnosis
      in Student's t test. There were statistically significant relationship with the
      histopathology of the lesion and the SI ratio in Student's t test (p = 0.027).
      CONCLUSIONS: DWI is an effective method in differentiation of benign and
      malignant testicular masses. Important information can be obtained about nature
      of testis masses with quantitative measurements of the ADC and ratio of SI.

PMID- 22983487
TI  - Retrobulbar vasculature using 7-T magnetic resonance imaging with dedicated eye
      surface coil.
AB  - PURPOSE: To determine the resolution and utility of using a dedicated, single
      loop eye coil at 7 T to image the posterior ocular structures and vascular
      anatomy. METHODS: Imaging was performed on eight subjects (age range 26-54 years,
      four female, four male) with 7 T using a transmit head coil for excitation and a
      dedicated 5-cm eye surface receive coil. Acquisition parameters at 7 T for 3D
      spoiled gradient echo (3D-SPGR) sequences were optimized. RESULTS: It was
      possible to delineate the retina, sclera, and choroid, and fine details within
      the anterior and posterior segments of the eye. Retro-orbital and posterior
      ocular anatomy remained well visualized despite motion and susceptibility
      artifacts of anterior ocular structures. The ophthalmic arteries and their first
      order branches were consistently visualized and improved with registration and
      summation of repeat scans. Furthermore, the central retinal vessels could be
      visualized. Intravenous gadolinium contrast reagent did not noticeably improve
      image quality. CONCLUSIONS: High-resolution 7-T MRI with a dedicated eye coil can
      provide unique high-resolution noninvasive images of retro-orbital and posterior
      ocular structural and vascular anatomy and is able to resolve structures as small
      as the central retina vein.

PMID- 22983490
TI  - Computational design of a Diels-Alderase from a thermophilic esterase: the
      importance of dynamics.
AB  - A novel computational Diels-Alderase design, based on a relatively rare form of
      carboxylesterase from Geobacillus stearothermophilus, is presented and
      theoretically evaluated. The structure was found by mining the PDB for a suitable
      oxyanion hole-containing structure, followed by a combinatorial approach to find
      suitable substrates and rational mutations. Four lead designs were selected and
      thoroughly modeled to obtain realistic estimates of substrate binding and
      prearrangement. Molecular dynamics simulations and DFT calculations were used to
      optimize and estimate binding affinity and activation energies. A large quantum
      chemical model was used to capture the salient interactions in the crucial
      transition state (TS). Our quantitative estimation of kinetic parameters was
      validated against four experimentally characterized Diels-Alderases with good
      results. The final designs in this work are predicted to have rate enhancements
      of ~ 10(3)-10(6) and high predicted proficiencies. This work emphasizes the
      importance of considering protein dynamics in the design approach, and provides a
      quantitative estimate of the how the TS stabilization observed in most de novo
      and redesigned enzymes is decreased compared to a minimal, 'ideal' model. The
      presented design is highly interesting for further optimization and applications
      since it is based on a thermophilic enzyme (T (opt) = 70  degrees C).

PMID- 22983491
TI  - Extraction and validation of substructure profiles for enriching compound
      libraries.
AB  - Compounds known to be potent against a specific protein target may potentially
      contain a signature profile of common substructures that is highly correlated to
      their potency. These substructure profiles may be useful in enriching compound
      libraries or for prioritizing compounds against a specific protein target. With
      this objective in mind, a set of compounds with known potency against six
      selected kinases (2 each from 3 kinase families) was used to generate binary
      molecular fingerprints. Each fingerprint key represents a substructure that is
      found within a compound and the frequency with which the fingerprint occurs was
      then tabulated. Thereafter, a frequent pattern mining technique was applied with
      the aim of uncovering substructures that are not only well represented among
      known potent inhibitors but are also unrepresented among known inactive compounds
      and vice versa. Substructure profiles that are representative of potent
      inhibitors against each of the 3 kinase families were thus extracted. Based on
      our validation results, these substructure profiles demonstrated significant
      enrichment for highly potent compounds against their respective kinase targets.
      The advantages of using our approach over conventional methods in analyzing such
      datasets and its application in the mining of substructures for enriching
      compound libraries are presented.

PMID- 22983492
TI  - M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate
      cancer.
AB  - Molecular imaging allows clinicians to visualize the progression of tumours and
      obtain relevant information for patient diagnosis and treatment. Owing to their
      intrinsic optical, electrical and magnetic properties, nanoparticles are
      promising contrast agents for imaging dynamic molecular and cellular processes
      such as protein-protein interactions, enzyme activity or gene expression. Until
      now, nanoparticles have been engineered with targeting ligands such as antibodies
      and peptides to improve tumour specificity and uptake. However, excessive loading
      of ligands can reduce the targeting capabilities of the ligand and reduce the
      ability of the nanoparticle to bind to a finite number of receptors on cells.
      Increasing the number of nanoparticles delivered to cells by each targeting
      molecule would lead to higher signal-to-noise ratios and would improve image
      contrast. Here, we show that M13 filamentous bacteriophage can be used as a
      scaffold to display targeting ligands and multiple nanoparticles for magnetic
      resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide
      magnetic nanoparticles assemble along the M13 coat, and its distal end is
      engineered to display a peptide that targets SPARC glycoprotein, which is
      overexpressed in various cancers. Compared with nanoparticles that are directly
      functionalized with targeting peptides, our approach improves contrast because
      each SPARC-targeting molecule delivers a large number of nanoparticles into the
      cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged
      for others, making this platform attractive for in vivo high-throughput screening
      and molecular detection.

PMID- 22983493
TI  - Upregulation of vascular endothelial growth factor receptor-3 in the spinal cord
      of Lewis rats with experimental autoimmune encephalomyelitis.
AB  - We investigated the spatiotemporal expression of vascular endothelial growth
      factor receptor-3 (VEGFR-3) in the spinal cord of Lewis rats with experimental
      autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. VEGFR
      3 mRNA and protein were constitutively expressed in gray matter neurons and in a
      few white matter astrocytes. Induction of VEGFR-3 occurred predominantly in
      perivascular infiltrated macrophages in the spinal cord white matter during the
      inductive phase of EAE. VEGFR-3 expression was also induced in activated
      microglial cells in the gray and white matter, mainly in the peak phase. In
      addition, reactive astrocytes in the white matter, but not in the gray matter,
      expressed VEGFR-3 as disease severity increased. These data suggest that VEGFR-3
      is involved in the recruitment of monocytic macrophages and in glial reactions
      during EAE.

PMID- 22983494
TI  - Maternal pre-pregnancy body mass index and offspring temperament and behavior at
      1 and 2 years of age.
AB  - Recent research suggests that fetal exposure to increased maternal body mass
      index (BMI) during pregnancy may be associated with psychopathology later in
      life. When this link first emerges, and if it is due to intrauterine exposures or
      confounding variables is not known. We therefore assessed associations between
      maternal pre-pregnancy BMI and: (1) temperament at 1 year of age, and (2) Child
      Behavior Checklist internalizing and externalizing scales at age 2 in the 2900
      mothers and infants enrolled in the Western Australian Pregnancy Study. Pre
      pregnancy BMI was positively associated with externalizing scores (beta = 0.131,
      95 % CI 0.013-0.249) at age 2, even after adjustment for confounders, but not
      with internalizing scores or an increased risk of difficult temperament. These
      data suggest that fetal exposure to increased maternal BMI is associated with
      elevated levels of behavior problems as early as age 2, and that this may be
      linked to the intrauterine environment.

PMID- 22983495
TI  - Combining features from ERP components in single-trial EEG for discriminating
      four-category visual objects.
AB  - Categorization of images containing visual objects can be successfully recognized
      using single-trial electroencephalograph (EEG) measured when subjects view
      images. Previous studies have shown that task-related information contained in
      event-related potential (ERP) components could discriminate two or three
      categories of object images. In this study, we investigated whether four
      categories of objects (human faces, buildings, cats and cars) could be mutually
      discriminated using single-trial EEG data. Here, the EEG waveforms acquired while
      subjects were viewing four categories of object images were segmented into
      several ERP components (P1, N1, P2a and P2b), and then Fisher linear discriminant
      analysis (Fisher-LDA) was used to classify EEG features extracted from ERP
      components. Firstly, we compared the classification results using features from
      single ERP components, and identified that the N1 component achieved the highest
      classification accuracies. Secondly, we discriminated four categories of objects
      using combining features from multiple ERP components, and showed that
      combination of ERP components improved four-category classification accuracies by
      utilizing the complementarity of discriminative information in ERP components.
      These findings confirmed that four categories of object images could be
      discriminated with single-trial EEG and could direct us to select effective EEG
      features for classifying visual objects.

PMID- 22983497
TI  - Organic layer serves as a hotspot of microbial activity and abundance in Arctic
      tundra soils.
AB  - Tundra ecosystem is of importance for its high accumulation of organic carbon and
      vulnerability to future climate change. Microorganisms play a key role in carbon
      dynamics of the tundra ecosystem by mineralizing organic carbon. We assessed both
      ecosystem process rates and community structure of Bacteria, Archaea, and Fungi
      in different soil layers (surface organic layer and subsurface mineral soil) in
      an Arctic soil ecosystem located at Spitsbergen, Svalbard during the summer of
      2008 by using biochemical and molecular analyses, such as enzymatic assay,
      terminal restriction fragment length polymorphism (T-RFLP), quantitative
      polymerase chain reaction (qPCR), and pyrosequencing. Activity of hydrolytic
      enzymes showed difference according to soil type. For all three microbial
      communities, the average gene copy number did not significantly differ between
      soil types. However, archaeal diversities appeared to differ according to soil
      type, whereas bacterial and fungal diversity indices did not show any variation.
      Correlation analysis between biogeochemical and microbial parameters exhibited a
      discriminating pattern according to microbial or soil types. Analysis of the
      microbial community structure showed that bacterial and archaeal communities have
      different profiles with unique phylotypes in terms of soil types. Water content
      and hydrolytic enzymes were found to be related with the structure of bacterial
      and archaeal communities, whereas soil organic matter (SOM) and total organic
      carbon (TOC) were related with bacterial communities. The overall results of this
      study indicate that microbial enzyme activity were generally higher in the
      organic layer than in mineral soils and that bacterial and archaeal communities
      differed between the organic layer and mineral soils in the Arctic region.
      Compared to mineral soil, peat-covered organic layer may represent a hotspot for
      secondary productivity and nutrient cycling in this ecosystem.

PMID- 22983498
TI  - Aldehyde dehydrogenase protein superfamily in maize.
AB  - Maize (Zea mays ssp. mays L.) is an important model organism for fundamental
      research in the agro-biotechnology field. Aldehydes were generated in response to
      a suite of environmental stresses that perturb metabolism including salinity,
      dehydration, desiccation, and cold and heat shock. Many biologically important
      aldehydes are metabolized by the superfamily of NAD(P)(+)-dependent aldehyde
      dehydrogenases. Here, starting from the database of Z. mays, we identified 28
      aldehyde dehydrogenase (ALDH) genes and 48 transcripts by the in silico cloning
      method using the ALDH-conserved domain amino acid sequence of Arabidopsis and
      rice as a probe. Phylogenetic analysis shows that all 28 members of the ALDH gene
      families were classified to ten distinct subfamilies. Microarray data and
      quantitative real-time PCR analysis reveal that ZmALDH9, ZmALDH13, and ZmALDH17
      genes involve the function of drought stress, acid tolerance, and pathogens
      infection. These results suggested that these three ZmALDH genes might be
      potentially useful in maize genetic improvement.

PMID- 22983496
TI  - Detection of metals and metalloproteins in the plasma of stroke patients by mass
      spectrometry methods.
AB  - Stroke is the leading cause of adult disability, worldwide. Metalloproteins and
      metals play key roles in epigenetic events in living organisms, including
      hypertension, the most important modifiable risk factor for stroke. Thus,
      metalloproteins may be important target biomarkers for disease diagnosis. The
      primary goal of this study was to assess metal containing proteins in blood
      plasma, detected by ICP-MS, followed by ESIMS for peptide/protein identification.
      We then compared the relative concentration differences between samples from
      patients with ischemic stroke, hemorrhagic stroke and stroke mimics. In 29 plasma
      samples (10 stroke mimics, 10 ischemic stroke and 9 hemorrhagic stroke patients)
      previously collected from patients who presented to the University of Cincinnati
      Emergency Department within 12 hours of symptom onset for a plasma banking
      project. For the metal associated protein study, Mg, Mn, Cu, Se concentrations
      were statistically different when compared between stroke mimics vs. ischemic
      stroke patients and ischemic stroke patients vs. hemorrhagic stroke patients. Pb
      concentrations were statistically different when compared between stroke mimics
      vs. ischemic stroke patients and Mo levels were statistically the same among the
      three groups. In addition, we also report concentration levels and preliminary
      correlation studies for total elemental analysis among the three sets of
      patients. This pilot study demonstrates that mass spectrometry methods may be
      highly valuable in detecting novel stroke biomarkers in blood plasma. Expanded
      studies are warranted to confirm these findings.

PMID- 22983499
TI  - Correlation between hand/wrist and panoramic radiographs in severe secondary
      hyperparathyroidism.
AB  - OBJECTIVES: Hand/wrist and dental radiographs are important for osteoporosis
      analysis in secondary hyperparathyroidism (SHPT). This study evaluated whether a
      correlation exists between the effects of the disease on the hands and jaws, and
      investigated the association between osteoporosis progression in the hands and
      parathyroid hormone (PTH) levels in chronic kidney disease (CKD) patients.
      MATERIALS AND METHODS: Four panoramic radiographic parameters (mental index,
      mandibular cortical index, trabecular bone pattern, and calcification/resorption)
      and four corresponding hand/wrist radiographic parameters (metacarpal cortical
      thickness, phalangeal cortical index, trabecular bone pattern, and
      calcification/resorption) were applied to investigate possible correlation
      between the effects of SHPT on the jaws and hands/wrists, by Spearman's
      correlation coefficient. PTH levels and the hand/wrist radiographic parameters
      were also tested by spearman's correlation coefficient (p < 0.05). The presence
      of brown tumors, vascular calcifications, and acroosteolysis on the hands was
      also evaluated. RESULTS: Mandibular cortical index was strongly correlated with
      the phalangeal cortical index (p = 0.000). Phalangeal cortical index and
      trabecular bone pattern of hand/wrist correlated with PTH levels (0.002 and
      0.000, respectively). Brown tumors occurred in four CKD patients, while both
      vascular calcifications and acroosteolysis were observed in 19 patients.
      CONCLUSION: There is a significant correlation between the morphological changes
      caused by secondary hyperparathyroidism in hand and jaw bones. The morphological
      status can be assessed using the mandibular cortical index, besides the
      phalangeal cortical index. The latter correlates well with parathyroid hormone
      levels of advanced chronic kidney disease. CLINICAL RELEVANCE: Panoramic images
      reveal morphological changes in the jaw bone, indicating likewise changes in the
      hand/wrist in severe secondary hyperparathyroidism. The severity of the bone
      changes may be a reflection of the parathyroid hormone levels in advanced chronic
      kidney disease.

PMID- 22983500
TI  - Accuracy of HIV-related risk behaviors reported by female sex workers, Iran: a
      method to quantify measurement bias in marginalized populations.
AB  - We quantified discrepancies in reported behaviors of female sex workers (FSW) by
      comparing 63 face-to-face interviews (FTFI) to in-depth interviews (IDI), with
      corroboration of the directions and magnitudes of reporting by a panel of
      psychologists who work with FSW. Sensitivities, specificities, positive and
      negative predictive values (PPV and NPV) were assessed for FTFI responses using
      IDI as a "gold standard". Sensitivities were lowest in reporting symptoms of
      sexually transmitted infections (63.9 %), finding sex partners in venues (52.4 %)
      and not receiving HIV test results (66.7 %). Specificities (all >83 %) and PPVs
      (all >74.0 %) were higher than NPV. FSW significantly under-reported number of
      clients, sexual contacts and non-condom use sex acts with clients and number of
      days engaging in sex work in the preceding week. This study provides a quantified
      gauge of reporting biases in FSW behaviors. Such estimates and methods help
      better understand true HIV risk in marginalized populations and calibrate survey
      estimates accordingly.

PMID- 22983501
TI  - HIV testing among patients infected with Neisseria gonorrhoeae: STD Surveillance
      Network, United States, 2009-2010.
AB  - We used data from the STD Surveillance Network to estimate HIV testing among
      patients being tested or treated for gonorrhea. Of 1,845 gonorrhea-infected
      patients identified through nationally notifiable disease data, only 51% were
      tested for HIV when they were tested or treated for gonorrhea. Among the 10
      geographic sites in this analysis, the percentage of patients tested for HIV
      ranged from 22-63% for men and 20-79% for women. Nearly 33% of the un-tested
      patients had never been previously HIV-tested. STD clinic patients were more
      likely to be HIV-tested than those in other practice settings.

PMID- 22983502
TI  - Individual, network, and neighborhood correlates of exchange sex among female non
      injection drug users in Baltimore, MD (2005-2007).
AB  - The "HIV risk environment" has been characterized as a dynamic interplay between
      structural and network factors. However, most HIV prevention research has not
      examined the independent and combined impact of network and structural factors.
      We aimed to identify individual, network, and neighborhood correlates of exchange
      sex (>=1 exchange sex partner, past 90 days) among female non-injection drug
      users (NIDUs). We used baseline data from 417 NIDUs enrolled in a randomized HIV
      prevention trial in Baltimore (2005-2007). Surveys ascertained demographic
      variables, drug/sex risk behaviors, neighborhood perceptions, and social/sexual
      network characteristics. Correlates of exchange sex were identified with
      descriptive statistics and log-binomial regression. Our findings suggest that sex
      and drug relationships among female NIDUs are interlinked and may be difficult to
      modify without altering social norms. Strengthening ties that provide social
      support but not drug support and reducing ties that provide both drug and social
      support may facilitate reductions in individual-level HIV-risk behaviors.

PMID- 22983504
TI  - A BINOL-based chiral polyammonium receptor for highly enantioselective
      recognition and fluorescence sensing of (S,S)-tartaric acid in aqueous solution.
AB  - A chiral ditopic polyammonium receptor featuring two [9]aneN(3) moieties
      separated by a (S)-BINOL linker is able to selectively bind and sense in water
      (S,S)-tartaric acid over its (R,R)/meso forms.

PMID- 22983503
TI  - Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell
      activation and IFN-gamma production in mice.
AB  - IL-33, a recently described member of the IL-1 family, has been identified as a
      cytokine endowed with pro-Th2 type functions. To date, there are only limited
      data on its role in physiological and pathological hepatic immune responses. In
      this study, we examined the role of IL-33 in immune-mediated liver injury by
      exploring the model of concanavalin A (Con A)-induced hepatitis. We observed that
      the level of IL-33 expression in the liver was dramatically increased at 12 h
      after Con A injection. Meanwhile, ST2L, the receptor of IL-33, was significantly
      up-regulated in lymphocytes including T and natural killer T (NKT) cells,
      especially in NKT cells. Moreover, administration of recombinant IL-33
      exacerbated Con A-induced hepatitis, while pretreatment of IL-33-blocking
      antibody or psST2-Fc plasmids showed a protective effect probably by inhibiting
      the activation of late stage of T cells and NKT cells and also decreasing the
      production of the cytokine IFN-gamma. Furthermore, depletion of NKT cells
      abolished the protective effect of IL-33-blocking antibody, and IL-33 failed to
      exacerbate Con A-induced hepatitis in IFN-gamma(-/-) mice. These data suggested
      the critical roles of NKT cells and IFN-gamma in the involvement of IL-33 in Con
      A-induced hepatitis. Blockade of IL-33 may represent a novel therapeutic strategy
      through IL-33/ST2L signal to prevent immune-mediated liver injury.

PMID- 22983505
TI  - Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound
      guided fine-needle aspiration specimens from patients with unresectable
      pancreatic cancer.
AB  - BACKGROUND: Although recent reports indicate that K-ras mutation status is a
      biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation
      subtypes have been published. In addition, there are no reports that analyze
      overall survival and prognostic factors according to K-ras mutation status and
      subtypes in only unresectable pancreatic cancer (PC) determined from tissues
      obtained by endoscopic ultrasound-guided fine-needle aspiration. METHODS: We
      retrospectively analyzed 242 patients who were diagnosed as having unresectable
      PC with available histological diagnosis. Clinical data collected included sex,
      age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen
      (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM
      staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V,
      and G12R), and overall survival. We analyzed the negative prognostic factors for
      reduced overall survival in unresectable PC patients using these data. RESULTS:
      From multivariate analysis, CA19-9 >=1000 U/ml (hazard ratio [HR] 1.78, 95 %
      confidence interval [CI] 1.28-2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI
      1.58-3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03-3.01, P = 0.04)
      were negative prognostic factors, indicating a reduced survival. Among the
      patients who had K-ras mutation subtypes, CA19-9 >=1000 U/ml (HR 1.65, 95 % CI
      1.12-2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44-3.14, P < 0.01),
      and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11-2.28) were
      negative prognostic factors for overall survival. CONCLUSIONS: K-ras mutation
      status and subtypes may be associated with survival duration in pancreatic cancer
      patients.

PMID- 22983506
TI  - The prevalences [correction] and patient characteristics of primary
      immunodeficiency diseases in Turkey--two centers study.
AB  - PURPOSE: Primary immunodeficiency diseases (PIDs) are inherited disorders of the
      immune system resulting in increased susceptibility to unusual infections and
      predisposition to autoimmunity and malignancies. The European Society for
      Immunodeficiencies (ESID) has developed an internet-based database for clinical
      and research data on patients with PID. This study aimed to provide a minimum
      estimate of the prevalence of each disorder and to determine the clinical
      characteristics and outcomes of patients with PID in Turkey. METHODS: Clinical
      features of 1435 patients with primary immunodeficiency disorders are registered
      in ESID Online Patient Registry by the Pediatric Immunology Departments of the
      Medical Faculties of Uludag University and Ege University Between 2004 and 2010.
      These two centers are the major contributors reporting PID patients to ESID
      database from Turkey. RESULTS: Predominantly antibody immunodeficiency (73.5 %)
      was the most common category followed by autoinflammatory disorders (13.3 %),
      other well defined immunodeficiencies (5.5 %), congenital defects of phagocyte
      number, function or both 3.5 %), combined T and B cell immunodeficiencies (2 %),
      defects in innate immunity (1 %), and diseases of immune dysregulation (0.7 %).
      Patients between 0 and 18 years of age constitued 94 % of total and the mean age
      was 9.2 +/- 6 years. The consanguinity rate within the registered patients was
      14.3 % (188 of 1130 patients). The prevalance of all PID cases ascertained from
      the registry was 30.5/100.000. The major cause of the mortality was severe
      infection which was seen in forty-two of seventy five deceased patients. The
      highest mortality was observed in patients with severe combined
      immunodeficiencies and ataxia-telangiectasia. CONCLUSION: Promoting the awareness
      of PID among the medical professionals and the general public is required if
      premature death and serious morbidity occurs due to late diagnosis of the wider
      spectrum of PID are to be avoided.

PMID- 22983507
TI  - Clinical variability of family members with the C104R mutation in transmembrane
      activator and calcium modulator and cyclophilin ligand interactor (TACI).
AB  - PURPOSE: Common Variable Immunodeficiency Disorder (CVID) is a complex disorder
      that predisposes patients to recurrent and severe infections. The C104R mutation
      in the transmembrane activator and calcium modulator and cyclophilin ligand
      interactor (TACI) is the most frequent mutation identified in patients with CVID.
      We carried out a detailed immunological and molecular study in a family with a
      C104R mutation. METHODS: We have undertaken segregation analysis of a kindred
      with C104R mutations of the TACI gene. Detailed immunological and molecular
      investigations were carried out for this kindred and the clinical phenotype was
      compared to the genotype. RESULTS: Segregation analysis of our kindred showed
      that inheriting single or double copy of the C104R mutation does not consign an
      individual to CVID. All heterozygotes in the family were phenotypically
      different, ranging from asymptomatic to ill-health. A family member with a wild
      type TACI variant had CVID-related phenotype including IgA deficiency and type 1
      diabetes. Interestingly, a family member with the homozygous C104R/C104R variant
      did not meet the criteria for CVID because he had excellent, albeit unsustained,
      vaccine responses to T cell dependent and T cell independent vaccine antigens
      despite profound hypogammaglobulinemia. CONCLUSION: The C104R mutation does not
      correlate with the clinical phenotypes in this family.

PMID- 22983511
TI  - Funny bones.

PMID- 22983512
TI  - Sexual health and contraception.
AB  - Sexual health encompasses 'sexual development and reproductive health, as well as
      the ability to develop and maintain meaningful interpersonal relationships;
      appreciate one's own body; interact with both genders in respectful and
      appropriate ways; express affection, love and intimacy in ways consistent with
      one's own values'. The 2008 WHO Consensus Statement additionally noted that
      'responsible adolescent intimate relationships' should be 'consensual, non
      exploitative, honest, pleasurable and protected against unintended pregnancy and
      STDs if any type of intercourse occurs'. Young people (YP) must, therefore, be
      able to access sexual health information and services that meet their needs. For
      most YP, interest in sexual activity begins with puberty, and this is associated
      with increasingly sexualised behaviour, including exploration of themselves and
      others. Most YP find this a confusing time, and so it is important that health
      professionals are able to offer advice regarding the wide range of sexual health
      issues, including sexuality, choice of partner, contraception, risk and
      management of sexually transmitted infections (STI) in a confident and
      approachable manner. YP have never had so much choice or information available to
      them, and this can be confusing for them. There is good evidence that YP who get
      information from their parents are likely to initiate sexual activity later than
      their peers who access information from their friends. However, there is also
      evidence that some YP would prefer to get sexual health information from health
      professionals. It is therefore imperative that all health professionals who see
      YP have an awareness of sexual health issues, and know where to signpost YP
      should they need more specialist sexual health advice and/or treatment. Where
      appropriate, one-to-one sexual health advice should be provided to YP on how to
      prevent and get tested for STIs, and how to prevent unwanted pregnancies. Advice
      should also be given on all methods of reversible contraception, including long
      acting reversible contraception, emergency contraception and other reproductive
      issues.

PMID- 22983508
TI  - High trefoil factor 1 (TFF1) expression in human retinoblastoma cells correlates
      with low growth kinetics, increased cyclin-dependent kinase (CDK) inhibitor
      levels and a selective down-regulation of CDK6.
AB  - Trefoil factor family (TFFs) peptides facilitate epithelial restitution, but also
      effect cell proliferation and apoptosis of normal and various cancer cell lines.
      In a recent study by our group, TFF2 expression was demonstrated in the murine
      retina, where it exhibits pro-proliferative and pro-apoptotic effects. In the
      present study, we investigated the expression and function of TFF peptides in
      eight human retinoblastoma cell lines. TFF1 was the only TFF peptide expressed at
      detectable levels in immunoblots of retinoblastoma cells. TFF1 expression levels
      were highly variable in different retinoblastoma cell lines and negatively
      correlated with cell growth curves. Recombinant human TFF1 had a negative effect
      on cell viability and caused a reduction in cell proliferation. Retinoblastoma
      cell lines with high TFF1 expression levels exhibited a selective down-regulation
      of cyclin-dependent kinase (CDK) 6, whereas CDK4 and CDK2 seem to be unaffected
      by TFF1 expression. In immunocytochemical studies, we observed a nuclear co
      localization of TFF1 and CDK2 in Cajal bodies (CBs). In high TFF1 expressing
      human retinoblastoma cell lines CBs were smaller and higher in number compared to
      retinoblastoma lines with low TFF1 expression, indicating differences in cell
      cycle status between the different retinoblastoma cell lines. Our data further
      support the notion for a potential tumor suppressor function of TFF1. The nuclear
      localization of TFF1 in CBs--considered to play a role in cell cycle progression,
      potentially acting as a platform for CDK-cyclin function-offers a new impetus in
      the ongoing search for potential TFF1 interacting proteins.

PMID- 22983513
TI  - Electric pulse training aids: more evidence needed, says CAWC.

PMID- 22983514
TI  - Call for views on strengthening TB eradication programme in England.

PMID- 22983517
TI  - 'State-of-the-nation' report identifies top cattle health and welfare issues.

PMID- 22983518
TI  - Tackling enterohaemorrhagic E coli at source.

PMID- 22983519
TI  - Reinforcing the message of good antibiotic use.

PMID- 22983520
TI  - Toxoplasmosis: BVA says risk from cats should not be overplayed.

PMID- 22983521
TI  - Maintaining momentum on welfare issues of dog breeding.

PMID- 22983522
TI  - Neonatal calves affected by haemorrhages unrelated to BNP.

PMID- 22983523
TI  - Keeping track of swine influenza viruses.

PMID- 22983524
TI  - Distribution of West Nile virus vector, Culex modestus, in England.

PMID- 22983525
TI  - Suicide and attitudes to animal euthanasia.

PMID- 22983527
TI  - Canine health awards.

PMID- 22983528
TI  - Regulation of disinfectants.

PMID- 22983529
TI  - Aberrant methylation and loss expression of RKIP is associated with tumor
      progression and poor prognosis in gastric cardia adenocarcinoma.
AB  - Raf kinase inhibitory protein (RKIP) has been identified as a member of a novel
      class of molecules which implicated in cancer progression and suppress the
      metastatic spread of tumors. The aim of this study was to investigate the
      promoter methylation and expression of RKIP, determine the prognostic
      significance of RKIP in gastric cardia adenocarcinoma (GCA). MSP approach and
      immunohistochemistry methods were used respectively to examine methylation status
      and protein expression of RKIP in GCA tissues. The frequency of RKIP methylation
      in GCA tumor tissues (62.1 %) was significantly higher than that in corresponding
      normal tissues (4.1 %) and was associated with TNM stage, histological
      differentiation, depth of invasion, LN metastasis, distant metastasis or
      recurrence, and upper gastrointestinal cancers (UGIC) family history. Positive
      staining of RKIP in GCA tumor tissues (34.5 %) was significantly decreased than
      that in corresponding normal tissues (84.1 %) and was associated with RKIP
      methylation. RKIP may act as a tumor suppressor gene in GCA by regulation of the
      Raf-1/MEK/ERK signaling pathway. GCA patients in stage III and IV, with positive
      UGIC family history, and hypermethylation and down-expression of RKIP were most
      likely to develop metastatic disease and also showed the worse survival. RKIP
      methylation in GCA was an independent prognostic marker for survival using
      multivariate Cox regression analysis (P = 0.04). In all, aberrant
      hypermethylation of RKIP may be one of the mechanisms that lead to loss or down
      expression of the gene in GCA especially in individuals with UGIC family history.
      Additionally, hypermethylation and loss of RKIP expression may be used as a
      marker to predict clinical outcome of GCA.

PMID- 22983530
TI  - Manifest for evidence-based child psychiatry in France.

PMID- 22983531
TI  - Reporting and analysis of trials using stratified randomisation in leading
      medical journals: review and reanalysis.
AB  - OBJECTIVES: To assess how often stratified randomisation is used, whether
      analysis adjusted for all balancing variables, and whether the method of
      randomisation was adequately reported, and to reanalyse a previously reported
      trial to assess the impact of ignoring balancing factors in the analysis. DESIGN:
      Review of published trials and reanalysis of a previously reported trial.
      SETTING: Four leading general medical journals (BMJ, Journal of the American
      Medical Association, Lancet, and New England Journal of Medicine) and the second
      Multicenter Intrapleural Sepsis Trial (MIST2). PARTICIPANTS: 258 trials published
      in 2010 in the four journals. Cluster randomised, crossover, non-randomised,
      single arm, and phase I or II trials were excluded, as were trials reporting
      secondary analyses, interim analyses, or results that had been previously
      published in 2010. MAIN OUTCOME MEASURES: Whether the method of randomisation was
      adequately reported, how often balanced randomisation was used, and whether
      balancing factors were adjusted for in the analysis. RESULTS: Reanalysis of MIST2
      showed that an unadjusted analysis led to larger P values and a loss of power.
      The review of published trials showed that balanced randomisation was common,
      with 163 trials (63%) using at least one balancing variable. The most common
      methods of balancing were stratified permuted blocks (n=85) and minimisation
      (n=27). The method of randomisation was unclear in 37% of trials. Most trials
      that balanced on centre or prognostic factors were not adequately analysed; only
      26% of trials adjusted for all balancing factors in their primary analysis.
      Trials that did not adjust for balancing factors in their analysis were less
      likely to show a statistically significant result (unadjusted 57% v adjusted 78%,
      P=0.02). CONCLUSION: Balancing on centre or prognostic factors is common in
      trials but often poorly described, and the implications of balancing are poorly
      understood. Trialists should adjust their primary analysis for balancing factors
      to obtain correct P values and confidence intervals and to avoid an unnecessary
      loss in power.

PMID- 22983532
TI  - Cosmetic approval.

PMID- 22983533
TI  - Good medicine: homeopathy.

PMID- 22983534
TI  - Terminally ill people shouldn't have to travel abroad for assisted dying.

PMID- 22983535
TI  - Associations between partner-venue specific personal responsibility beliefs and
      transmission risk behavior by HIV-positive men who have sex with men (MSM).
AB  - Personal responsibility beliefs of HIV-positive individuals to protect sex
      partners are an important determinant of engagement in transmission risk
      behavior. However, the degree to which such beliefs vary across different
      partners is unknown. HIV-positive men who have sex with men (n = 248) completing
      an online survey rated their personal responsibility beliefs for partners met in
      up to four different ways: (a) in a bar; (b) through the internet; (c) in a
      public sex environment (PSE); or (d) through friends or family. For those
      reporting two or more partner-meeting venues in the prior 3 months (n = 98),
      about a third reported variation in responsibility ratings. Means among the
      venues were compared in pairwise fashion, with the strongest beliefs accruing to
      partners met through friends or family and the least with partners met in PSEs.
      These results provide further evidence that identifying ways to increase personal
      responsibility beliefs is an important goal, as well as is the application of
      Bandura's theory of moral agency to HIV transmission risk behavior.

PMID- 22983536
TI  - Effect of a clinic-wide social marketing campaign to improve adherence to
      antiretroviral therapy for HIV infection.
AB  - This demonstration study tested the impact of a 5-month clinic-wide social
      marketing campaign at improving adherence to antiretroviral therapy (ART). The
      intervention included a video, posters, pens, mugs, and lapel buttons with the
      campaign slogan "Live the Solution: Take Your Pills Every Day." Participants self
      reported adherence over a 4-week interval, the primary outcome, with a visual
      analogue scale. Pre- and post-intervention surveys were completed by 141
      participants. Adherence did not change over time (absolute mean change -2.02 %,
      paired t test P = 0.39). Among the 39.7 % of participants who correctly
      identified the campaign slogan on the post-intervention survey, adherence
      increased by 3.3 %, while it decreased in the other participants by 5.5 % (paired
      t test P = 0.07). The well-received campaign did not increase short-term
      adherence to ART, but adherence tended to increase in participants who were more
      engaged with the intervention. Future interventions should engage patients more
      completely and have a more potent effect on adherence.

PMID- 22983537
TI  - Understanding of norms regarding sexual practices among gay men: literature
      review.
AB  - Since there is little evidence about gay community norms across the world, we
      reviewed published literature in this area and discuss implications for
      prevention and research. Eight databases were searched for articles and 16 were
      considered suitable for analysis. All used quantitative methodology and seven
      were based on a published theoretical framework. The most common theory employed
      by four out of the seven papers was the Theory of Reasoned Action. All papers
      reviewed examined norms on condom use but norms on other risk reduction practices
      were not explored in these papers. Seven (44 %) studies found those men who
      perceived strong social support from their peers, were less likely to engage in
      unprotected anal intercourse. This finding suggests that social support from
      partners and community members plays a role in shaping safe sex norms. Better
      understanding of norms may help to redress HIV behaviour change programmes,
      particularly at the time when HIV diagnoses rates are increasing in most gay
      communities across the world.

PMID- 22983538
TI  - Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1beta-induced
      IL-2 production in T-cells.
AB  - Mild zinc deficiency in humans negatively affects IL-2 production resulting in
      declined percentages of cytolytic T cells and decreased NK cell lytic activity,
      which enhances the susceptibility to infections and malignancies. T-cell
      activation is critically regulated by zinc and the normal physiological zinc
      level in T-cells slightly lies below the optimal concentration for T-cell
      functions. A further reduction in zinc level leads to T-cell dysfunction and
      autoreactivity, whereas high zinc concentrations (100 MUM) were shown to inhibit
      interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this
      study, we investigated the molecular mechanism by which zinc regulates the IL
      1beta-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient
      T-cells increased intracellular zinc levels by altering the expression of zinc
      transporters, particularly Zip10 and Zip12. A zinc signal was observed in the
      murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1beta, measured by
      specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the
      phosphorylation of MAPK p38 and NF-kappaB subunit p65, which triggers the
      transcription of IL-2 and strongly increases its production. These results
      indicate that short-term zinc supplementation to zinc-deficient T-cells leads to
      a fast rise in zinc levels which subsequently enhance cytokine production. In
      conclusion, low and excessive zinc levels might be equally problematic for zinc
      deficient subjects, and stabilized zinc levels seem to be essential to avoid
      negative concentration-dependent zinc effects on T-cell activation.

PMID- 22983539
TI  - Association of AFF1 rs340630 and AFF3 rs10865035 polymorphisms with systemic
      lupus erythematosus in a Chinese population.
AB  - The aim of this study was to evaluate whether two single-nucleotide polymorphisms
      (SNPs), AF4/FMR2 family, member 1 (AFF1) rs340630 and AF4/FMR2 family, member 3
      (AFF3) rs10865035, show significant evidence for association with systemic lupus
      erythematosus (SLE) in a Chinese population. A total of 868 Chinese patients with
      SLE and 975 geographically and ethnically matched healthy control subjects were
      enrolled in the current study. The genotypes of these two SNPs were determined by
      Sequenom MassArray technology. Significant evidence for association of AFF3
      rs10865035 with SLE was detected (for A versus G, P = 4.81 * 10(-4), odds ratio
      (OR) 1.26, 95% confidence interval (95% CI) 1.11-1.44). However, no association
      between AFF1 rs340630 and SLE was found in the Chinese population (for A versus
      G, P = 0.79, OR 0.98, 95% CI 0.86-1.12). No significant evidence for association
      of AFF3 rs10865035 polymorphism with any clinical features was detected. By
      targeting a variant with convincing evidence for association with rheumatoid
      arthritis, significant association of AFF3 rs10865035 with SLE was detected in
      the Chinese population, indicating that AFF3 might be a common autoimmunity gene.
      Further case-control studies based on larger sample sizes in diverse ethnic
      populations are required to clarify the role of AFF1 rs340630 in SLE.

PMID- 22983540
TI  - Chimney technique in the endovascular management of complex aortic disease.
AB  - The objective of this study was to systematically review the literature reporting
      on the chimney technique and perform an analysis of the outcomes. A search of
      electronic databases was undertaken to identify all studies reporting on the
      outcome of the chimney technique. The selected articles were divided into those
      reporting on the treatment of aortic pathology involving the visceral and those
      involving the supra-aortic branches. Twenty-one articles reporting on the
      treatment of juxta/supra-renal aorta and aortic arch disease in 102 and 37
      patients, respectively, were identified. In the visceral group, an overall
      technical success rate of 91% was achieved, the perioperative major morbidity and
      mortality rates were 17 and 5%, respectively, and an early type I endoleak
      developed in 13 patients (13%). During follow-up, one patient died of intestinal
      ischemia. In the supra-aortic group, the technical success rate was recorded in
      95%, and three patients (8%) developed an early type I endoleak. Three patients
      (13%) required conversion to open surgery during follow-up. In conclusion, this
      technique may be viewed as a complementary technique in high-surgical-risk
      patients.

PMID- 22983541
TI  - Incisional hernia postrepair of abdominal aortic occlusive and aneurysmal
      disease: five-year incidence.
AB  - The aim of this study was to report the five-year incidence of incisional hernia
      after vascular repair of abdominal aortic occlusive (AOD) and aneurysmal disease
      (AAA), and to determine the factors associated with the development of this
      complication. Consecutive patients who underwent AAA and AOD at the University of
      Manitoba, Canada, between January 1999 and December 2002, were recruited and
      evaluated by clinical examination one week, one month and six months after the
      surgery, and through medical records review thereafter. The development of
      postoperative incisional hernia was recorded and analyzed. Two-hundred four
      patients, with a mean age of 70.1 years, provided consent for the study. The
      overall five-year incidence of incisional hernia was 69.1% and the overall median
      failure time was 48 months. The median failure time was 48 months for AOD and 36
      months for AAA (P < 0.01). The urgent and ruptured AAA repair had a higher five
      year incidence of incisional hernia as compared with AOD or elective AAA repair
      (P < 0.01). A history of bilateral inguinal hernia was significantly associated
      with incisional hernia (P < 0.05). Men and patients who were 65 years and older
      had a higher five-year incidence of incisional hernia (P < 0.01). Age >=65 years,
      male gender, hypertension and past bilateral inguinal hernia repair double the
      risk for the development of incisional hernia (hazard ratio = 2.1. 2.2, 1.7 and
      2.8, respectively). In conclusion, the five-year incidence of incisional hernia
      after vascular repair of AOD or AAA is 69.1%, and tends to occur late after
      vascular repair.

PMID- 22983542
TI  - PROPATEN graft: an unlikely heparin-induced thrombocytopenia culprit.

PMID- 22983543
TI  - Subacute anterior spinal cord ischemia with lower limb monoplegia: a clinical
      dilemma and challenging scenario.
AB  - A 70-year-old woman presented with crescendo right lower limb monoplegia.
      Magnetic resonance imaging depicted anterior spinal artery syndrome with an 8.5
      cm Crawford type II thoracoabdominal aortic aneurysm (TAAA). A staged hybrid
      procedure was performed, following which she had total exclusion of her TAAA and
      full resolution of her monoplegia. Clinical presentations of TAAAs can be diverse
      and require detailed clinical knowledge and lateral thinking to unearth
      unorthodox presentations. This erratic presentation of a TAAA with anterior
      spinal artery syndrome outlines particular challenges with management and
      portrays the need for tailored utilization of contemporary techniques to deal
      with the growing complexity of TAAAs.

PMID- 22983544
TI  - Successful endovascular treatment of a ruptured gigantic pseudoaneurysm of the
      common iliac artery secondarily complicated by infection.
AB  - We report our experience with a case of emergent endovascular treatment of a
      large ruptured pseudoaneurysm of the common iliac artery. A 65-year-old male was
      admitted to the surgical department in hypovolemic shock, due to active
      retroperitoneal bleeding. A computerized tomography scan with intravenous
      contrast revealed a ruptured gigantic pseudoaneurysm of the right common iliac
      artery, with a maximal diameter of 7 cm and retroperitoneal hematoma. An
      intraoperative angiogram revealed active extravasation through the neck of the
      pseudoaneurysm, which was successfully sealed with the placement of a stent graft
      (Medtronic Endurant((r)))limb component. Infection of the pseudoaneurysm sac
      after one month was successfully treated with catheter drainage. No shortterm
      relapse occurred. Endovascular management should be part of the basic surgical
      armamentarium on emergent basis, since it provides a fast and safe solution,
      especially when a patient's co-morbitities preclude open management and
      hemodynamic and anatomical status allows endovascular treatment.

PMID- 22983545
TI  - Endovascular treatment of an anastomotic iliac pseudoaneurysm after surgical
      aortic repair using a Cardiatis multilayer stent.
AB  - The Cardiatis multilayer stent (Cardiatis, Isnes, Belgium) is a cobalt, self
      expandable bare stent made of two interconnected layers without any covering that
      allows a pressure decrease and thrombus formation into an aneurysmal sac, while
      improving laminar flow in the main artery and surrounding vital branches. We
      report a case of an anastomotic iliac pseudoaneurysm successfully treated with
      the deployment of a Cardiatis multilayer stent.

PMID- 22983546
TI  - A clampless and sutureless aortic anastomosis technique using an endograft
      connector for aortoiliac occlusive disease in which the aorta cannot be clamped
      or sewn due to calcification or scarring.
AB  - Bypass surgery in aortoiliac or aortofemoral occlusive disease can be technically
      demanding and hazardous due to huge calcifications and/or patient co-morbidities.
      We report about mid-term results of a telescoping sutureless aortic anastomosis
      technique using endografts as connectors to address such challenging situations.
      This is a single-center experience (2004-2011) in seven patients (63 +/- 6 years)
      requiring aortoiliac (three) or aortofemoral (four) bypass surgery. In six cases,
      an aortic stent graft was telescoped into the infrarenal aorta and partly
      deployed within the aorta and partly outside the aorta. In the first case, a
      bifurcated stent graft was deployed and the iliac legs were prolonged extra
      anatomically with surgical grafts to reach the femoral bifurcation. In the
      following five cases, a tapered tubular stent graft was deployed through the
      aortic wall, landing inside a bifurcated surgical graft that was extra
      anatomically connected to the iliac or femoral arteries. In the last case, which
      presented a hostile abdomen and high-risk for extensive surgery, a similar
      technique was used, but on the iliac artery level. In that case, an iliac stent
      graft re-loaded 'upside down' was deployed through the left common iliac wall,
      landing distally inside a hand-made 10 * 10 mm bifurcated surgical graft that was
      extra-anatomically connected to the left external iliac artery and to the right
      femoral artery. The distal anastomoses on the seven cases were performed either
      with running sutures (ten) or with VORTEC (four). Telescoping aortic and/or iliac
      anastomosis was successful in all patients. There was no perioperative mortality.
      One patient developed postoperative hyperperfusion of the left leg and
      necessitated fasciotomy. During a mean follow-up of 1.8 +/- 2 years (minimum: 270
      days, maximum: 7.1 years), all of the grafts remained patent and there was
      neither stent-graft migration nor stenosis on the level of the aortic or
      iliofemoral connection. One patient showed disease progression and required
      percutaneous transluminal angioplasty on the external iliac artery during follow
      up. The uneventful perioperative course in these seven patients, with a follow-up
      of up to six years, underscores that this new technique can be considered in
      patients with aortoiliac or aortofemoral occlusive disease and in whom clamping
      and/or anastomosis is expected to be cumbersome or impossible.

PMID- 22983547
TI  - Pathophysiology and treatment of edema following femoropopliteal bypass surgery.
AB  - Substantial lower-limb edema affects the majority of patients who undergo
      peripheral bypass surgery. Edema has impairing effects on the microvascular and
      the macrovascular circulation, causes discomfort and might delay the
      rehabilitation process of the patient. However, the pathophysiology of this edema
      is not well understood. The Cochrane Library and Medline were used to retrieve
      literature on edema following peripheral bypass surgery. Factors other than local
      wound healing alone are suggested in the literature to play a role, given the
      severity and duration of this edema. Hyperemia, microvascular permeability,
      reperfusion-associated inflammation and lymphatic disruptions are likely to
      facilitate the development of edema. Preventive methods could be lymphatic
      sparing surgery, intraoperative antioxidative therapy and postoperative
      elevation. Successful treatment strategies to reduce postoperative edema are
      based on lymph massage and external compression. In conclusion, the
      pathophysiology of edema following peripheral surgery is not fully understood,
      although reperfusion-associated inflammation and lymphatic disruptions are likely
      to play a crucial role. When future less-invasive techniques prove to be
      successful, postoperative edema might be minimized. Until then, a careful
      lymphatic-sparing dissection should be executed when performing a peripheral
      bypass reconstruction. Postoperatively, the use of compression stockings and leg
      elevation are currently the golden standards.

PMID- 22983548
TI  - Compression of the dorsalis pedis artery: a novel cause of blue toe syndrome.
AB  - Blue toe syndrome (BTS) is an important vascular condition characterized by
      painful blue discoloration of one or more digits. It is frequently due to emboli
      and is important because of the risk of progressive ischemia and tissue loss. A
      53-year-old male presented with recurrent episodes of painful blue discoloration
      and blistering of the skin of the right hallux. On examination, the patient was
      found to have a cool, blue-purple great toe; all peripheral pulses were present.
      The patient was investigated for coagulopathy and potential sources of emboli,
      but the only abnormality was significant stenosis of the dorsalis pedis artery
      due to extrinsic compression by the extensor hallucis brevis tendon. In the
      absence of any other embolic source or abnormality, we believe that this case
      presents a novel and potentially remediable cause of BTS and indicates the need
      for a careful search for an underlying lesion when common causes of BTS have been
      excluded.

PMID- 22983549
TI  - On the evolutionary significance of the size and planarity of the proline ring.
AB  - Proline is a proteinogenic amino acid in which the side chain forms a ring, the
      pyrrolidine ring. This is a five-membered ring made up of four carbons and one
      nitrogen. Here, we study the evolutionary significance of this ring size. It is
      shown that the size of the pyrrolidine ring has the advantage of being nearly
      planar and strain-free, based on a general mathematical assertion saying that the
      angular sum of a polygon is maximum if it is planar and convex. We also provide a
      sketch of the proof to this assertion. The optimality of the ring size of proline
      can be derived from a triangle inequality for angles. Quasi-planarity is
      physiologically significant because it allows an easier and evolutionarily old
      type of fit into binding grooves of proteins with which proline-rich proteins
      interact. Finally, we present a comparison with other planar, nearly planar and
      non-planar biomolecules such as neurotransmitters, hormones and toxins,
      involving, for example, aromatic rings, cyclopentanone and 1,3-dioxole.

PMID- 22983551
TI  - Ano-coccygeal support in the treatment of idiopathic chronic posterior anal
      fissure: a prospective non-randomised controlled pilot trial.
AB  - BACKGROUND: Idiopathic chronic anal fissure is believed to be a consequence of a
      traumatic acute anodermal tear followed by recurrent inflammation and poor
      healing due to relative tissue ischaemia secondary to internal sphincter spasm.
      This pilot trial compared the efficacy of a novel manufactured ano-coccygeal
      support attached to a standard toilet seat (Colorec) to the standard procedure of
      lateral internal sphincterotomy (LIS) for chronic anal fissure. METHODS: Fifty
      three patients with confirmed chronic anal fissures were enrolled and assigned,
      based on their preference, to the test group and the control group. Each patient
      was reviewed after therapy, and follow-up was scheduled at 4, 6 and 8 weeks and
      at 6 months. RESULTS: The fissure healing rate was 100% in both groups. There
      were no statistically significant differences between the test group (n = 30,
      median age 42 years; range 20-71 years) and the control group (n = 22, median age
      38 years; range 23-60 years) with regards to resolution of rectal bleeding at
      defaecation after 4 weeks (86.6 vs. 72.7%, p = 0.698), and by week 6, bleeding
      had resolved in 100% of patients in both groups. There was no statistically
      significant difference between the test group and the control group with regards
      to pain scores at 4, 6 and 8 weeks (4.30 +/- 0.79, 2.03 +/- 0.80, 0.43 +/- 0.50
      vs. 3.50 +/- 0.74, 1.68 +/- 0.56, 0.50 +/- 0.51, p = 0.054) and to time until
      complete healing of fissures (5.60 +/- 1.52 weeks vs. 5.91 +/- 1.57 weeks, p =
      0.479). After continuous use of the ano-coccygeal support over 6 months, no
      patients in the test group had recurrent fissures. No complications were observed
      during the trial. CONCLUSIONS: Results of both methods were comparable and
      demonstrated that the ano-coccygeal support is at least as effective as LIS,
      without any short-term complications. Larger and randomised trials on the use of
      ano-coccygeal support for chronic anal fissures are awaited.

PMID- 22983552
TI  - Introducing the revised WEBbook of Biologics.

PMID- 22983553
TI  - Do work-related factors affect care-seeking in general practice for back pain or
      upper extremity pain?
AB  - OBJECTIVES: Musculoskeletal pain conditions remain a major cause of care-seeking
      in general practice. Not all patients with musculoskeletal pain (MP) seek care at
      their general practitioner (GP), but for those who do, the GP's knowledge of what
      work-related factors might have influenced the patient's decision to seek care
      could be important in order to give more well-founded advice to our patients. The
      objective of this study was to elucidate the effects of workloads on care-seeking
      for back pain or upper extremity pain during an eighteen-month follow-up period.
      METHODS: This is a prospective study with a baseline questionnaire and eighteen
      month follow-up. Among the registered patients of 8 GPs, we identified 8,517
      persons between 17 and 65 years of age, who all received the questionnaire. A
      total of 5,068 (59.5 %) persons answered. During the eighteen months of follow
      up, we used the International Classification for Primary Care (ICPC) to identify
      all care-seekers with either back pain or upper extremity pain. Of these, all
      currently employed persons were included in our analysis, in all 4,325 persons.
      For analysis, we used Cox proportional hazards regression analysis. Analyses were
      stratified by gender. RESULTS: High levels of heavy lifting, defined as the upper
      tertile on a categorical scale, were associated with care-seeking for back pain
      (HR 1.90 [95 % CI: 1.14-3.15]) and upper extremity pain (HR 2.09 [95 % CI: 1.30
      3.38]) among males, but not in a statistically significant way among females.
      Repetitive work and psychosocial factors did not have any statistically
      significant impact on care-seeking for neither back pain nor upper extremity
      pain. CONCLUSION: Work-related factors such as heavy lifting do, to some extent,
      contribute to care-seeking with MP. We suggest that asking the patient about
      physical workloads should be routinely included in consultations dealing with MP.

PMID- 22983555
TI  - Setting sail for glucose homeostasis with the AKAP150-PP2B-anchor.
AB  - Glucose-stimulated insulin secretion, controlled by multiple protein
      phosphorylation events, is critical for the regulation of glucose homeostasis.
      Protein kinase A (PKA) is known to play a role in beta cell physiology, but the
      role of its anchoring protein is not fully understood. Hinke et al (2012)
      illustrate the significance of A-kinase anchoring protein 150 in tethering
      protein phosphatase 2B to mediate nutrient-stimulated insulin secretion and thus
      modulate glucose homeostasis.

PMID- 22983556
TI  - Molecular recognition driven self-assembly and chiral induction in naphthalene
      diimide amphiphiles.
AB  - Naphthalene diimide amphiphiles functionalized with the dipicolylethylenediamine
      motif self-assemble with tunable chirality upon molecular recognition with
      various adenosine phosphates and competitive guest binding leads to the dynamic
      helix reversal of these assemblies.

PMID- 22983554
TI  - The Arf GAP ASAP1 provides a platform to regulate Arf4- and Rab11-Rab8-mediated
      ciliary receptor targeting.
AB  - Dysfunctional trafficking to primary cilia is a frequent cause of human diseases
      known as ciliopathies, yet molecular mechanisms for specific targeting of sensory
      receptors to cilia are largely unknown. Here, we show that the targeting of
      ciliary cargo, represented by rhodopsin, is mediated by a specialized system, the
      principal component of which is the Arf GAP ASAP1. Ablation of ASAP1 abolishes
      ciliary targeting and causes formation of actin-rich periciliary membrane
      projections that accumulate mislocalized rhodopsin. We find that ASAP1 serves as
      a scaffold that brings together the proteins necessary for transport to the cilia
      including the GTP-binding protein Arf4 and the two G proteins of the Rab family-
      Rab11 and Rab8--linked by the Rab8 guanine nucleotide exchange factor Rabin8.
      ASAP1 recognizes the FR ciliary targeting signal of rhodopsin. Rhodopsin FR-AA
      mutant, defective in ASAP1 binding, fails to interact with Rab8 and translocate
      across the periciliary diffusion barrier. Our study implies that other rhodopsin
      like sensory receptors may interact with this conserved system and reach the
      cilia using the same platform.

PMID- 22983557
TI  - Air-liquid interface biofilm formation by psychrotrophic pseudomonads recovered
      from spoilt meat.
AB  - The ability to colonise the surface of liquids has obvious advantages for
      bacteria and biofilm formation at the meniscus and air-liquid (A-L) interface is
      common amongst environmental pseudomonads. Bacteria from this genus also colonise
      raw meat and in this work the ability of these to produce biofilms was assessed.
      Sixty isolates were recovered from vacuum-packed venison, phenotypically
      characterised and shown by hierarchical cluster analysis to represent a diverse
      collection of psychrotrophic spoilt venison-associated pseudomonads. Of these, 12
      % were found to produce biofilms limited to the meniscus region of the microcosm
      walls, 31 % produced attached biofilms with significant extensions across the A-L
      interface and 45 % produced unattached 'floating' biofilms. A combined
      statistical analysis of growth, biofilm strength and attachment levels revealed
      that growth affected strength but not attachment, and that there was a
      significant relationship between attachment and strength. Some environmental
      pseudomonads are known to utilise cellulose as a biofilm matrix component and
      here 28 % of the SVP isolates were found to express cellulose by epifluorescent
      microscopy. This survey suggests that biofilm formation may be more common in
      psychrotrophic meat-associated isolates than amongst the wider pseudomonad
      community from which spoilage bacteria might be recruited. This may reflect a
      selective advantage of bacterial aggregations such as biofilms in environments
      subject to high levels of physical disturbance. Aggregations may be more
      resistant to competition and dehydration stress than individual bacteria, whilst
      fragments of these aggregations may prove more effective in the colonisation of
      new habitats.

PMID- 22983559
TI  - Improving the characteristics of an organic nano floating gate memory by a self
      assembled monolayer.
AB  - We demonstrate a novel approach to improve the characteristics of the gold
      nanoparticle-based organic transistor memory devices by using self-assembled
      monolayers (SAM) with different functional groups as interfacial modifier. SAM
      based interfacial engineering significantly improved the hysteresis, memory
      window, and on/off ratio of a nano floating gate memory (NFGM) at zero gate
      voltage. This NFGM showed a large memory window of up to 190 V and on/off current
      ratio of 10(5) during writing and erasing with an operation voltage of 100 V of
      gate bias in a short time, less than 1 s. Furthermore, the devices show excellent
      nonvolatile behavior for bistable switching. The ON and OFF state can be stably
      maintained for 10(3) s with an I(on)/I(off) current ratio of 10(6) for a
      pentafluorophenyl trimethoxysilane modified device. The results suggested the
      importance of SAM-modified interface for the memory performance of NFGMs.

PMID- 22983558
TI  - A web-delivered care management and patient self-management program for recurrent
      depression: a randomized trial.
AB  - OBJECTIVE This study assessed the impact of an Internet-delivered care management
      and patient self-management program, eCare for Moods, on patients treated for
      recurrent or chronic depression. METHODS Patients with recurrent or chronic
      depression were randomly assigned to eCare (N=51) or usual specialty mental
      health care (N=52). The 12-month eCare program integrates with ongoing depression
      care, links to patients' electronic medical records, and provides clinicians with
      panel management and decision support. Participants were interviewed at baseline
      and six, 12, 18, and 24 months after enrollment. Telephone interviewers blind to
      treatment used a timeline follow-back method to estimate depression severity on a
      6-point scale for each of the 105 study weeks (including the baseline).
      Differences between groups in weekly severity over two years were examined by
      generalized estimating equations. RESULTS Participants in eCare experienced more
      reduction in depressive symptoms (estimate=-.74 on the 6-point scale over two
      years; 95% confidence interval [CI]=-1.38 to -.09, p=.025) and were less often
      depressed (-.24 over two years; CI=-.46 to -.03, p=.026). At 24 months, 43% of
      eCare and 30% of usual-care participants were depression free; the number needed
      to treat to attain one additional depression-free participant was 8. eCare
      participants had other favorable outcomes: improved general mental health
      (p=.002), greater satisfaction with specialty care (p=.003) and with learning new
      coping skills (p<.001), and more confidence in managing depression (p=.006).
      CONCLUSIONS Internet-delivered care management can help improve outcomes of
      patients treated for recurrent or chronic depression.

PMID- 22983560
TI  - From bedside to bench: reverse engineering medical progress.

PMID- 22983561
TI  - Season of birth effect on psychotic-like experiences in Japanese adolescents.
AB  - A number of studies have investigated seasonality of birth in schizophrenia. Most
      of the studies have consistently observed an excess of winter births, often
      associated with decreased summer births. We postulated that psychotic-like
      experiences (PLEs), subclinical hallucinatory and delusional experiences, may
      also be affected by birth season. In the present study, we assessed the season of
      birth effect on the prevalence of PLEs using data from the cross-sectional survey
      of 19,436 Japanese adolescents. As a result, significant excess of winter births
      was observed in the prevalence of PLEs, accompanied by a decreased proportion of
      summer births. The odds ratios for the prevalence of PLEs were estimated to be
      1.11, which was on the same order with those for the development of schizophrenia
      in the previous meta-analytic studies. To our knowledge, this is the first to
      show the seasonality of birth in the prevalence of PLEs and implicate the winter
      birth effect on subclinical stage of schizophrenia.

PMID- 22983562
TI  - How spectroscopy and microspectroscopy of degraded wood contribute to understand
      fungal wood decay.
AB  - Nuclear magnetic resonance, mid and near infrared, and ultra violet (UV) spectra
      of wood contain information on its chemistry and composition. When solid wood
      samples are analysed, information on the molecular structure of the
      lignocellulose complex of wood e.g. crystallinity of polysaccharides and the
      orientation of the polymers in wood cell walls can also be gained. UV and
      infrared spectroscopy allow also for spatially resolved spectroscopy, and state
      of-the-art mapping and imaging systems have been able to provide local
      information on wood chemistry and structure at the level of wood cells (with IR)
      or cell wall layers (with UV). During the last decades, these methods have also
      proven useful to follow alterations of the composition, chemistry and physics of
      the substrate wood after fungi had grown on it as well as changes of the
      interactions between the wood polymers within the lignocellulose complex caused
      by decay fungi. This review provides an overview on how molecular spectroscopic
      methods could contribute to understand these degradation processes and were able
      to characterise and localise fungal wood decay in its various stages starting
      from the incipient and early ones even if the major share of research focussed on
      advanced decay. Practical issues such as requirements in terms of sample
      preparation and sample form and present examples of optimised data analysis will
      also be addressed to be able to detect and characterise the generally highly
      variable microbial degradation processes within their highly variable substrate
      wood.

PMID- 22983564
TI  - Intronic splicing enhancers, cognate splicing factors and context-dependent
      regulation rules.
AB  - Most human genes produce multiple splicing isoforms with distinct functions. To
      systematically understand splicing regulation, we conducted an unbiased screen
      and identified >100 intronic splicing enhancers (ISEs), clustered by sequence
      similarity. All ISEs functioned in multiple cell types and in heterologous
      introns, and patterns of distribution and conservation across pre-mRNA regions
      were similar to those of exonic splicing silencers. Consistently, all ISEs
      inhibited use of splice sites from exons. Putative trans-factors of each ISE
      group were identified and validated. Five distinct groups were recognized by
      hnRNP H and hnRNP F, whose C-terminal domains were sufficient to render context
      dependent activities of ISEs. The sixth group was controlled by factors that
      either activate or suppress splicing. We provide a comprehensive picture of
      general ISE activities and suggest new models of how single elements can function
      oppositely, depending on locations and binding factors.

PMID- 22983563
TI  - A transcription factor-based mechanism for mouse heterochromatin formation.
AB  - Heterochromatin is important for genome integrity and stabilization of gene
      expression programs. We have identified the transcription factors Pax3 and Pax9
      as redundant regulators of mouse heterochromatin, as they repress RNA output from
      major satellite repeats by associating with DNA within pericentric
      heterochromatin. Simultaneous depletion of Pax3 and Pax9 resulted in dramatic
      derepression of major satellite transcripts, persistent impairment of
      heterochromatic marks and defects in chromosome segregation. Genome-wide analyses
      of methylated histone H3 at Lys9 showed enrichment at intergenic major satellite
      repeats only when these sequences retained intact binding sites for Pax and other
      transcription factors. Additionally, bioinformatic interrogation of all histone
      methyltransferase Suv39h-dependent heterochromatic repeat regions in the mouse
      genome revealed a high concordance with the presence of transcription factor
      binding sites. These data define a general model in which reiterated arrangement
      of transcription factor binding sites within repeat sequences is an intrinsic
      mechanism of the formation of heterochromatin.

PMID- 22983565
TI  - Conception through build of an automated liquids processing system for compound
      management in a low-humidity environment.
AB  - Boehringer Ingelheim's Automated Liquids Processing System (ALPS) in Ridgefield,
      Connecticut, was built to accommodate all compound solution-based operations
      following dissolution in neat DMSO. Process analysis resulted in the design of
      two nearly identical conveyor-based subsystems, each capable of executing 1400 *
      384-well plate or punch tube replicates per batch. Two parallel-positioned
      subsystems are capable of independent execution or alternatively executed as a
      unified system for more complex or higher throughput processes. Primary ALPS
      functions include creation of high-throughput screening plates, concentration
      response plates, and reformatted master stock plates (e.g., 384-well plates from
      96-well plates). Integrated operations included centrifugation,
      unsealing/piercing, broadcast diluent addition, barcode print/application,
      compound transfer/mix via disposable pipette tips, and plate sealing. ALPS key
      features included instrument pooling for increased capacity or fail-over
      situations, programming constructs to associate one source plate to an array of
      replicate plates, and stacked collation of completed plates. Due to the
      hygroscopic nature of DMSO, ALPS was designed to operate within a 10% relativity
      humidity environment. The activities described are the collaborative efforts that
      contributed to the specification, build, delivery, and acceptance testing between
      Boehringer Ingelheim Pharmaceuticals, Inc. and the automation integration vendor,
      Thermo Scientific Laboratory Automation (Burlington, ON, Canada).

PMID- 22983566
TI  - The use of cold plasma technology to reduce carryover in screening assays.
AB  - The accurate transfer of biological reagents represents a fundamental step in the
      drug screening process, and the elimination of carryover is critical for the
      generation of accurate measurements of biological activity. The introduction of
      automated liquid robotics into screening laboratories has transformed the drug
      screening process, enabling accurate and reproducible transfer of liquids to
      become a high-throughput activity, but has also introduced a new challenge for
      drug discoverers: to establish screening workflows that limit analyte carryover
      for the generation of high-quality screening data. The widespread use of
      pipetting tips on automated liquid handlers often necessitates the use of
      optimized wash protocols for removing contaminants and frequently requires the
      use and disposal of large quantities of organic solvents. Furthermore, many
      chemical and biological reagents are recalcitrant to removal from pipetting tips
      by treatment with organic solvents. The use of cold atmospheric plasma technology
      provides an alternative approach for removal of contaminants and offers many
      advantages over traditional decontamination protocols commonly used during
      biological screening. This report describes the evaluation of a cold plasma tip
      cleaning system for reducing carryover in a range of biological screening assays
      requiring the transfer of low molecular weight compound, nucleic acid, and
      bacterial liquid transfers. The validation of this technology for biological
      screening assays is presented, and the impact of this technology for screening
      workflows is discussed. 

PMID- 22983567
TI  - Quality of core collections for effective utilisation of genetic resources
      review, discussion and interpretation.
AB  - Definition of clear criteria for evaluation of the quality of core collections is
      a prerequisite for selecting high-quality cores. However, a critical examination
      of the different methods used in literature, for evaluating the quality of core
      collections, shows that there are no clear guidelines on the choices of quality
      evaluation criteria and as a result, inappropriate analyses are sometimes made
      leading to false conclusions being drawn regarding the quality of core
      collections and the methods to select such core collections. The choice of
      criteria for evaluating core collections appears to be based mainly on the fact
      that those criteria have been used in earlier publications rather than on the
      actual objectives of the core collection. In this study, we provide insight into
      different criteria used for evaluating core collections. We also discussed
      different types of core collections and related each type of core collection to
      their respective evaluation criteria. Two new criteria based on genetic distance
      are introduced. The consequences of the different evaluation criteria are
      illustrated using simulated and experimental data. We strongly recommend the use
      of the distance-based criteria since they not only allow the simultaneous
      evaluation of all variables describing the accessions, but they also provide
      intuitive and interpretable criteria, as compared with the univariate criteria
      generally used for the evaluation of core collections. Our findings will provide
      genebank curators and researchers with possibilities to make informed choices
      when creating, comparing and using core collections.

PMID- 22983569
TI  - Determinants of muscle metaboreflex and involvement of baroreflex in boys and
      young men.
AB  - This study aimed to assess the arterial pressure (AP) determinants during the
      muscle metaboreflex in boys and men and to investigate the contribution of
      baroreflex and sympathovagal function to the metaboreflex-induced responses.
      Fourteen pre-adolescent boys and 13 men performed a protocol involving: baseline,
      isometric handgrip exercise, circulatory occlusion, and recovery. The same
      protocol was repeated without occlusion. During baseline, boys had lower beat-to
      beat AP, higher heart rate (HR), and lower low/high frequency HR variability.
      During exercise, a parasympathetic withdrawal was evident in both groups. In
      adults, HR was the key contributor to the pressure response, with no changes in
      stroke volume, whereas in boys, the lower HR increase was counterbalanced by an
      increase in stroke volume, resulting in similar relative increases in AP in both
      groups. In recovery, boys exhibited a faster rate of HR-decay, rapid vagal
      reactivation, and greater decrease in TPR than men. An overshoot in baroreceptor
      sensitivity was observed in men. The isolated metaboreflex resulted in a similar
      AP elevation in both age groups (by ~15 mmHg), and attenuated spontaneous
      baroreceptor sensitivity. However, during the metaboreflex, pre-adolescent males
      exhibited a lower increase in peripheral resistance and a greater bradycardic
      response than adults, and a fast restoration of vagal activity to non-occlusion
      levels. During metaboreflex, boys were capable of eliciting a pressure response
      similar to the one elicited by men; however, the interplay of the mechanisms
      underlying the rise in AP differed between the two groups with the vagal
      contribution being greater in the younger participants.

PMID- 22983570
TI  - Transient ischemic attacks from arterial gas embolism induced by glossopharyngeal
      insufflation and a possible method to identify individuals at risk.
AB  - Breath-hold divers report transient, severe neurological symptoms that could be
      caused by arterial gas embolism after glossopharyngeal insufflation. This
      technique is often used to overinflate the lungs and stretch the chest prior to
      breath-holding and can increase the transpulmonary pressure to around 7-8 kPa, so
      introducing risk of pulmonary barotrauma. Airway pressure, blood pressure and
      static spirometry (nitrogen dilution) were measured simultaneously in ten
      subjects attempting to identify individuals at risk. Compared to baseline, total
      lung capacity (TLC) after glossopharyngeal insufflation increased by 19 % along
      with increased vital capacity (23 %) and residual volume (6 %) (P < 0.05), while
      mean relaxed airway pressure (P (aw)) at TLC increased from 3.62 +/- 0.93 to 7.26
      +/- 2.04 kPa as a result of performing glossopharyngeal insufflation (P =
      0.0001). Blood pressure fell during glossopharyngeal insufflation and attained
      relaxed airway pressure correlated positively to baseline mean arterial pressure
      in the subjects. Two of the subjects had glossopharyngeal insufflation-related
      accidents before the study and two subjects (with the highest P (aw) during GI; 9
      and 10.3 kPa respectively) suffered glossopharyngeal insufflation-related
      accidents within 6 months after our study, with one suffering a non-fatal
      drowning accident. The principal finding of this study was that some subjects
      were able to use GI to reach P (aw) high enough to suggest a risk of pulmonary
      barotrauma, while other subjects would lose consciousness due to hypotension
      while still within safe limits of pulmonary pressure. This mechanism could offer
      an alternative explanation to drowning in breath-hold divers, and indicates that
      glossopharyngeal insufflation should be avoided or done with extreme caution.

PMID- 22983571
TI  - Evolutionary paths to mammalian cochleae.
AB  - Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to
      humans) in mammals has been a subject of research for many years. Recent advances
      in paleontological techniques, especially the use of micro-CT scans, now provide
      important new insights that are here reviewed. True mammals arose more than 200
      million years (Ma) ago. Of these, three lineages survived into recent geological
      times. These animals uniquely developed three middle ear ossicles, but these
      ossicles were not initially freely suspended as in modern mammals. The earliest
      mammalian cochleae were only about 2 mm long and contained a lagena macula. In
      the multituberculate and monotreme mammalian lineages, the cochlea remained
      relatively short and did not coil, even in modern representatives. In the lineage
      leading to modern therians (placental and marsupial mammals), cochlear coiling
      did develop, but only after a period of at least 60 Ma. Even Late Jurassic
      mammals show only a 270  degrees  cochlear coil and a cochlear canal length of
      merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state
      of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not
      realized until the early Cretaceous (~125 Ma). At that time, therian mammals
      arose and possessed a fully coiled cochlea. The evolution of modern features of
      the middle ear and cochlea in the many later lineages of therians was, however, a
      mosaic and different features arose at different times. In parallel with cochlear
      structural evolution, prestins in therian mammals evolved into effective
      components of a new motor system. Ultrasonic hearing developed quite late-the
      earliest bat cochleae (~60 Ma) did not show features characteristic of those of
      modern bats that are sensitive to high ultrasonic frequencies.

PMID- 22983573
TI  - The relationship between the severity of hemolysis, clinical manifestations and
      risk of death in 415 patients with sickle cell anemia in the US and Europe.
AB  - The intensity of hemolytic anemia has been proposed as an independent risk factor
      for the development of certain clinical complications of sickle cell disease,
      such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A
      composite variable derived from several individual markers of hemolysis could
      facilitate studies of the underlying mechanisms of hemolysis. In this study, we
      assessed the association of hemolysis with outcomes in sickle cell anemia. A
      hemolytic component was calculated by principal component analysis from
      reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and
      total bilirubin concentrations in 415 hemoglobin SS patients. Association of this
      component with direct markers of hemolysis and clinical outcomes was assessed. As
      primary validation, both plasma red blood cell microparticles and cell-free
      hemoglobin concentration were higher in the highest hemolytic component quartile
      compared to the lowest quartile (P<=0.0001 for both analyses). The hemolytic
      component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha
      thalassemia (P<=0.0005); it was higher with higher systemic pulse pressure, lower
      oxygen saturation, and greater values for tricuspid regurgitation velocity, left
      ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two
      year follow-up analysis showed that a high hemolytic component was associated
      with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval,
      CI: 1.2-9.5; P=0.02). The hemolytic component reflects direct markers of
      intravascular hemolysis in patients with sickle cell disease and allows for
      adjusted analysis of associations between hemolytic severity and clinical
      outcomes. These results confirm associations between hemolytic rate and pulse
      pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic
      pressures and mortality (Clinicaltrials.gov identifier: NCT00492531).

PMID- 22983574
TI  - Transcriptional regulation of miR-10a/b by TWIST-1 in myelodysplastic syndromes.
AB  - The transcription factor TWIST-1 is up-regulated in CD34(+) cells in
      myelodysplastic syndrome and is involved in resistance to apoptosis. There is
      evidence that TWIST-1 affects apoptosis via microRNAs (miRs). Expression of miRs
      was determined in myeloid cell lines and primary CD34(+) marrow cells from
      patients with myelodysplastic syndrome and healthy donors using NanoString/array
      and validated by real-time-polymerase chain reaction. Expression levels of miR10a
      and miR10b were significantly higher in CD34(+) marrow cells from 28 patients
      with myelodysplastic syndrome than in CD34(+) cells from healthy donors (P=0.05
      and P=0.012, respectively). Levels of miR10a/b correlated with TWIST-1 miR levels
      in CD34(+) myelodysplastic marrow cells (miR10a, R=+0.69, P<0.0001; miR10b,
      R=+0.56, P=0.0008). Inhibition of miR10a/10b in clonal cells interfered with
      proliferation and enhanced sensitivity to apoptosis, which involved NF-kappaB
      dependent p53 activation. These data support a role for miR10a/10b in the
      regulation of apoptosis in myelodysplastic syndrome and suggest the TWIST
      1/miR10a/b-axis as a therapeutic target in myelodysplastic syndrome.

PMID- 22983575
TI  - A prospective study of nutritional status in immunoglobulin light chain
      amyloidosis.
AB  - Weight loss is common in systemic immunoglobulin light chain amyloidosis but
      there are limited data on the impact of nutritional status on outcome. Using the
      Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively
      examined nutritional status in 110 consecutive newly-diagnosed, treatment-naive
      patients with immunoglobulin light chain amyloidosis attending the UK National
      Amyloidosis Centre. At study entry, 72 of 110 (66%) patients had a PG-SGA score
      of 4 or over, indicating malnutrition requiring specialist nutritional
      intervention. Number of amyloidotic organs, elevated alkaline phosphatase,
      presence of autonomic neuropathy and advanced Mayo disease stage were
      independently associated with poor nutritional status (P<0.05). Quality of life
      was substantially poorer among those with higher PG-SGA scores (P<0.001).
      Furthermore, PG-SGA score was a powerful independent predictor of patient
      survival (P=0.02). Malnutrition is prevalent and is associated with poor quality
      of life and reduced survival among patients with systemic immunoglobulin light
      chain amyloidosis. The PG-SGA score would be an appropriate tool to evaluate
      whether nutritional intervention could improve patient outcomes.

PMID- 22983576
TI  - Outcome of patients with low-risk myelodysplasia after azacitidine treatment
      failure.

PMID- 22983577
TI  - Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in
      adults.
AB  - A diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency
      during adulthood is unusual. We analyzed 17 cases of autoimmune
      lymphoproliferative syndrome caused by FAS deficiency diagnosed during adulthood
      in French reference centers for hereditary immunodeficiencies and for immune
      cytopenias. Twelve of the 17 patients had developed their first symptoms during
      childhood. The diagnosis of autoimmune lymphoproliferative syndrome had been
      delayed for a variety of reasons, including unusual clinical manifestations, late
      referral to a reference center, and the occurrence of somatic FAS mutations. The
      5 other patients presented their first symptoms after the age of 16 years. In
      these patients, three germline heterozygous FAS mutations were predicted to be
      associated with haploinsufficiency and a somatic event on the second FAS allele
      was observed in 2 cases. Autoimmune lymphoproliferative syndrome may well be
      diagnosed in adulthood. The occurrence of additional genetic events may account
      for the delayed disease onset.

PMID- 22983578
TI  - In utero and early postnatal presentation of autoimmune lymphoproliferative
      syndrome in a family with a novel FAS mutation.

PMID- 22983579
TI  - Plerixafor and granulocyte colony-stimulating factor for first-line steady-state
      autologous peripheral blood stem cell mobilization in lymphoma and multiple
      myeloma: results of the prospective PREDICT trial.
AB  - In Europe, the combination of plerixafor + granulocyte colony-stimulating factor
      is approved for the mobilization of hematopoietic stem cells for autologous
      transplantation in patients with lymphoma and myeloma whose cells mobilize
      poorly. The purpose of this study was to further assess the safety and efficacy
      of plerixafor + granulocyte colony-stimulating factor for front-line mobilization
      in European patients with lymphoma or myeloma. In this multicenter, open label,
      single-arm study, patients received granulocyte colony-stimulating factor (10
      MUg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given
      plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5
      after a morning dose of granulocyte colony-stimulating factor. The primary study
      objective was to confirm the safety of mobilization with plerixafor. Secondary
      objectives included assessment of efficacy (apheresis yield, time to
      engraftment). The combination of plerixafor + granulocyte colony-stimulating
      factor was used to mobilize hematopoietic stem cells in 118 patients (90 with
      myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment
      emergent plerixafor-related adverse events were reported in 24 patients. Most
      adverse events occurred within 1 hour after injection, were grade 1 or 2 in
      severity and included gastrointestinal disorders or injection-site reactions. The
      minimum cell yield (>= 2 * 10(6) CD34(+) cells/kg) was harvested in 98% of
      patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median
      of one apheresis. The optimum cell dose (>= 5 * 10(6) CD34(+) cells/kg for non
      Hodgkin's lymphoma or >= 6 * 10(6) CD34(+) cells/kg for myeloma) was harvested in
      89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this
      prospective, multicenter European study, mobilization with plerixafor +
      granulocyte colony-stimulating factor allowed the majority of patients with
      myeloma or non-Hodgkin's lymphoma to undergo transplantation with minimal
      toxicity, providing further data supporting the safety and efficacy of plerixafor
      + granulocyte colony-stimulating factor for front-line mobilization of
      hematopoietic stem cells in patients with non-Hodgkin's lymphoma or myeloma.

PMID- 22983580
TI  - Diagnosis and treatment of mucormycosis in patients with hematological
      malignancies: guidelines from the 3rd European Conference on Infections in
      Leukemia (ECIL 3).
AB  - Mucormycosis is an emerging cause of infectious morbidity and mortality in
      patients with hematologic malignancies. However, there are no recommendations to
      guide diagnosis and management. The European Conference on Infections in Leukemia
      assigned experts in hematology and infectious diseases to develop evidence-based
      recommendations for the diagnosis and treatment of mucormycosis. The guidelines
      were developed using the evidence criteria set forth by the American Infectious
      Diseases Society and the key recommendations are summarized here. In the absence
      of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or
      detection of the organism by culture from involved sites with identification of
      the isolate at the species level (no grading). Antifungal chemotherapy, control
      of the underlying predisposing condition, and surgery are the cornerstones of
      management (level A II). Options for first-line chemotherapy of mucormycosis
      include liposomal amphotericin B and amphotericin B lipid complex (level B II).
      Posaconazole and combination therapy of liposomal amphotericin B or amphotericin
      B lipid complex with caspofungin are the options for second line-treatment (level
      B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease
      (level A II). Reversal of underlying risk factors (diabetes control, reversal of
      neutropenia, discontinuation/taper of glucocorticosteroids, reduction of
      immunosuppressants, discontinuation of deferroxamine) is important in the
      treatment of mucormycosis (level A II). The duration of antifungal chemotherapy
      is not defined but guided by the resolution of all associated symptoms and
      findings (no grading). Maintenance therapy/secondary prophylaxis must be
      considered in persistently immunocompromised patients (no grading).

PMID- 22983581
TI  - Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced
      apoptosis in leukemia cells.
AB  - The multiple cellular targets affected by proteasome inhibition implicate a
      potential role for bortezomib, a first-in-class proteasome inhibitor, in
      enhancing antitumor activities in hematologic malignancies. Here, we examined the
      antitumor activity and drug targets of bortezomib in leukemia cells. Human
      leukemia cell lines were used for in vitro studies. Drug efficacy was evaluated
      by apoptosis assays and associated molecular events assessed by Western Blot.
      Gene silencing was performed by small interference RNA. Drug was tested in vivo
      in xenograft models of human leukemia cell lines and in primary leukemia cells.
      Clinical samples were assessed by immunohistochemical staining. Bortezomib
      differentially induced apoptosis in leukemia cells that was independent of its
      proteasome inhibition. Cancerous inhibitor of protein phosphatase 2A, a cellular
      inhibitor of protein phosphatase 2A, mediated the apoptotic effect of bortezomib.
      Bortezomib increased protein phosphatase 2A activity in sensitive leukemia cells
      (HL-60 and KG-1), but not in resistant cells (MOLT-3 and K562). Bortezomib's
      downregulation of cancerous inhibitor of protein phosphatase 2A and phospho-Akt
      correlated with its drug sensitivity. Furthermore, cancerous inhibitor of protein
      phosphatase 2A negatively regulated protein phosphatase 2A activity. Ectopic
      expression of CIP2A up-regulated phospho-Akt and protected HL-60 cells from
      bortezomib-induced apoptosis, whereas silencing CIP2A overcame the resistance to
      bortezomib-induced apoptosis in MOLT3 and K562 cells. Importantly, bortezomib
      exerted in vivo antitumor activity in HL-60 xenografted tumors and induced cell
      death in some primary leukemic cells. Cancerous inhibitor of protein phosphatase
      2A was expressed in leukemic blasts from bone marrow samples. Cancerous inhibitor
      of protein phosphatase 2A plays a major role in mediating bortezomib-induced
      apoptosis in leukemia cells.

PMID- 22983582
TI  - Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone
      B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the
      Arbeitsgemeinschaft Medikamentose Tumortherapie.
AB  - Currently, there is no standard systemic treatment for extranodal marginal zone B
      cell lymphoma of the mucosa-associated lymphoid tissue. Both rituximab and
      cladribine have shown some activity in this disease, but the combination has not
      been tested so far. In view of this, we initiated a phase II study to assess the
      activity and safety of rituximab and cladribine in patients with histologically
      verified mucosa-associated lymphoid tissue lymphoma. Treatment consisted of
      rituximab 375 mg/m(2) i.v. day 1 and cladribine 0.1 mg/kg s.c. days 1 - 4 every
      21 days. In case of complete remission after two courses, another two cycles of
      therapy were administered, while patients with a partial response or stable
      disease were scheduled to receive six cycles of treatment. Out of 40 evaluable
      patients (14 female, 26 male), 39 received treatment as scheduled while one
      patient died before initiation of therapy and was rated as having progressive
      disease in the intent-to-treat analysis. Twenty-one patients had gastric
      lymphoma, while 19 suffered from extragastric mucosa-associated lymphoid tissue
      lymphoma. Side effects consisted mainly of hematologic toxicity including
      leukopenia, lymphopenia, anemia and thrombocytopenia. Twenty-three patients had a
      complete remission (58%) and nine had a partial remission (23%) for an overall
      response rate of 81%, while five had stable disease (13%) and two progressed
      during therapy. After a median follow-up of 16.7 months (interquartile range:
      15.9 - 18.7 months), 35 patients are alive (88%) while four patients have died
      and one patient withdrew consent and did not allow further follow up. Our data
      demonstrate that rituximab plus cladribine is active and safe in patients with
      mucosa-associated lymphoid tissue lymphoma.

PMID- 22983584
TI  - The murine growth differentiation factor 15 is not essential for systemic iron
      homeostasis in phlebotomized mice.
AB  - In conditions of increased erythropoiesis, expression of hepcidin, the master
      regulator of systemic iron homeostasis, is decreased to allow for the release of
      iron into the blood stream from duodenal enterocytes and macrophages. It has been
      suggested that hepcidin suppression is controlled by growth differentiation
      factor 15 (GDF15), a member of the transforming growth factor-beta superfamily of
      cytokines that is secreted from developing erythroblasts. In this study, we
      analyzed iron-related parameters in mice deficient for GDF15 under steady-state
      conditions and in response to increased erythropoietic activity induced by blood
      loss. We demonstrate that GDF15 suppresses the hepatic mRNA expression of some
      BMP/TGFbeta target genes but not of hepcidin, and show that GDF15 is not required
      to balance iron homeostasis in response to blood loss.

PMID- 22983583
TI  - A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in
      previously treated patients with AL amyloidosis.
AB  - Immune-modulatory drugs are active in immunoglobulin light-chain amyloidosis and
      the addition of alkylating agents can potentiate their action. In this phase II
      prospective trial we used cyclophosphamide, lenalidomide and dexamethasone in the
      treatment of 21 patients who were refractory (n=13, 62%) or relapsed (n=8, 38%)
      after prior treatment including melphalan in all cases, bortezomib in 4 and
      thalidomide in 6. Median number of cycles administered was 4 (range 2-9 cycles).
      Severe adverse events were observed in 57% of patients, most common being
      neutropenia (29%). The hematologic response rate was 62%, with one complete
      response and 5 very good partial responses. Overall median survival was three
      years. The achievement of CR/VGPR was associated with a significant survival
      advantage. The combination of cyclophosphamide, lenalidomide and dexamethasone is
      an effective treatment for relapsed/refractory AL amyloidosis, and good quality
      hematologic response should be the aim of treatment in this setting.
      (clinicaltrials.gov identifier: NCT00607581).

PMID- 22983585
TI  - Identification of molecular and functional patterns of p53 alterations in chronic
      lymphocytic leukemia patients in different phases of the disease.
AB  - We analyzed TP53 mutations in 483 chronic lymphocytic leukemia patients at
      different phases of the disease and found a higher incidence of mutations at the
      later phases and a distinctive mutation profile in each phase. p53 function
      evaluated by immunoblotting and flow cytometry after cell irradiation was
      impaired in 28 of 109 cases. Three phenotypically different dysfunctions were
      observed: type I, associated with heterozygous missense TP53 mutations (typically
      present at diagnosis) and partially resistant to radiation-induced killing; types
      II and III, with a higher incidence of microdeletions, nonsense mutations and bi
      allelic TP53 defects (common in progressive and chemoresistant cases) and a
      complete radioresistance. Furthermore, in 4 of 28 patients, all chemoresistant,
      we found p53 dysfunctions without TP53 mutations. In chronic lymphocytic leukemia
      patients, a disease phase-specific variability in the p53 mutation profile and
      function takes place, and both analyses could be useful to guide treatment
      choices.

PMID- 22983586
TI  - Bone metabolism, growth rate and pubertal development in children with chronic
      myeloid leukemia treated with imatinib during puberty.

PMID- 22983587
TI  - Autologous blood cell transplantation versus HLA-identical sibling
      transplantation for acute myeloid leukemia in first complete remission: a
      registry study from the Center for International Blood and Marrow Transplantation
      Research.
AB  - The optimal post-remission treatment for acute myeloid leukemia in first complete
      remission remains uncertain. Previous comparisons of autologous versus allogeneic
      hematopoietic cell transplantation noted higher relapse, but lower treatment
      related mortality though using bone marrow grafts, with treatment-related
      mortality of 12-20%. Recognizing lower treatment-related mortality using
      autologous peripheral blood grafts, in an analysis of registry data from the
      Center for International Blood and Transplant Research, we compared treatment
      related mortality, relapse, leukemia-free survival, and overall survival for
      patients with acute myeloid leukemia in first complete remission (median ages 36
      44, range 19-60) receiving myeloablative HLA-matched sibling donor grafts (bone
      marrow, n=475 or peripheral blood, n=428) versus autologous peripheral blood
      (n=230). The 5-year cumulative incidence of treatment-related mortality was 19%
      (95% confidence interval, 16-23%), 20% (17-24%) and 8% (5-12%) for allogeneic
      bone marrow, allogeneic peripheral blood and autologous peripheral blood stem
      cell transplant recipients, respectively. The corresponding figures for 5-year
      cumulative incidence of relapse were 20% (17-24%), 26% (21-30%) and 45% (38-52%),
      respectively. At 5 years, leukemia-free survival and overall survival rates were
      similar: allogeneic bone marrow 61% (56-65%) and 64% (59-68%); allogeneic
      peripheral blood 54% (49-59%) and 59% (54-64%); autologous peripheral blood 47%
      (40-54%) and 54% (47-60%); P=0.13 and P=0.19, respectively. In multivariate
      analysis the incidence of treatment-related mortality was lower after autologous
      peripheral blood transplantation than after allogeneic bone marrow/peripheral
      blood transplants [relative risk 0.37 (0.20-0.69); P=0.001], but treatment
      failure (death or relapse) after autologous peripheral blood was significantly
      more likely [relative risk 1.32 (1.06-1.64); P=0.011]. The 5-year overall
      survival, however, was similar in patients who received autologous peripheral
      blood (n=230) [relative risk 1.23 (0.98-1.55); P=0.071] or allogeneic bone
      marrow/peripheral blood (n=903). In the absence of an HLA-matched sibling donor,
      autologous peripheral blood may provide acceptable alternative post-remission
      therapy for patients with acute myeloid leukemia in first complete remission.

PMID- 22983588
TI  - Influence of molecular subgroups on outcome of acute myeloid leukemia with normal
      karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation
      in primary induction failure or beyond first relapse.
AB  - Based on molecular aberrations, in particular the NPM1 mutation (NPM1(mut)) and
      the FLT3 internal tandem duplication (Flt3-ITD), prognostic subgroups have been
      defined among patients with acute myeloid leukemia with normal karyotype. Whereas
      these subgroups are known to play an important role in outcome in first complete
      remission, and also in the indication for allogeneic stem cell transplantation,
      data are limited on their role after transplantation in advanced disease. To
      evaluate the role of molecular subgroups of acute myeloid leukemia with normal
      karyotype after allogeneic stem cell transplantation beyond first complete
      remission, we analyzed the data from 141 consecutive adults (median age: 51.0
      years, range 18.4-69.3 years) who had received an allogeneic transplant either in
      primary induction failure or beyond first complete remission. A sequential
      regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine)
      followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for
      conditioning. After a median follow up of three years, overall survival from
      transplantation was 64 +/- 4%, 53 +/- 4% and 44 +/- 5% at one, two and four
      years, respectively. Forty patients transplanted in primary induction failure
      achieved an encouraging 2-year survival of 69%. Among 101 patients transplanted
      beyond first complete remission, 2-year survival was 81% among patients with the
      NPM1(mut)/FLT3(wt) genotype in contrast to 43% in other genotypes. Higher numbers
      of transfused CD34(+) cells (hazard ratio 2.155, 95% confidence interval 0.263
      0.964, P=0.039) and favorable genotype (hazard ratio 0.142, 95% confidence
      interval: 0.19-0.898, P=0.048) were associated with superior overall survival in
      multivariate analysis. In conclusion, patients with acute myeloid leukemia with
      normal karyotype can frequently be rescued after primary induction failure by
      allogeneic transplantation following FLAMSA-RIC. The prognostic role of
      NPM1(mut)/FLT3-ITD based subgroups was carried through after allogeneic stem cell
      transplantation beyond first complete remission.

PMID- 22983590
TI  - Pulmonary hypertension in POEMS syndrome.
AB  - POEMS syndrome is a rare clonal plasma cell disease. Patients with POEMS syndrome
      are at risk of developing pulmonary hypertension, but the data on its incidence
      and impact on outcome are limited. We reviewed records of 154 POEMS syndrome
      patients with complete duplex echocardiography data for estimation of pulmonary
      artery systolic pressure (sPAP) at the time of diagnosis. Forty-two (27%) of 154
      patients with pulmonary hypertension (estimated sPAP >=50 mmHg) were identified.
      Median age was 46 years (range 31-71 years). Patients with pulmonary hypertension
      were more likely to have peripheral edema (P=0.04), ascites (P=0.02), pleural
      effusion (P=0.005), and have longer time from onset to diagnosis (P=0.004) when
      compared with those without pulmonary hypertension. Restrictive abnormalities and
      decreased diffusion capacity of carbon monoxide were observed in 83% and 96%
      patients with pulmonary hypertension, compared with 50% and 72% in patients
      without pulmonary hypertension, respectively. Reversibility of pulmonary
      hypertension was observed after treatment of POEMS syndrome. After median follow
      of 32 months, survival of patients with pulmonary hypertension was worse than
      those without (median overall survival 54 months vs. median not reached,
      P=0.021). In conclusion, pulmonary hypertension is a common feature of POEMS
      syndrome, and is associated with signs of extravascular volume overload. Although
      active treatment of POEMS syndrome can reverse pulmonary hypertension, survival
      of these patients is worse than those without pulmonary hypertension.

PMID- 22983589
TI  - Survival of European patients diagnosed with myeloid malignancies: a HAEMACARE
      study.
AB  - Population-based information on the survival of patients with myeloid
      malignancies is rare mainly because some entities were not recognized as
      malignant until the publication of the third revision of the International
      Classification of Diseases for Oncology and World Health Organization
      classification in 2000. In this study we report the survival of patients with
      myeloid malignancies, classified by updated criteria, in Europe. We analyzed
      58,800 cases incident between 1995 to 2002 in 48 population-based cancer
      registries from 20 European countries, classified into HAEMACARE myeloid
      malignancy groupings. The period approach was used to estimate 5-year relative
      survival in 2000-2002. The relative overall survival rate was 37%, but varied
      significantly between the major groups: being 17% for acute myeloid leukemia, 20%
      for myelodysplastic/myeloproliferative neoplasms, 31% for myelodysplastic
      syndromes and 63% for myeloproliferative neoplasms. Survival of patients with
      individual disease entities ranged from 90% for those with essential
      thrombocythemia to 4% for those with acute myeloid leukemia with multilineage
      dysplasia. Regional European variations in survival were conspicuous for
      myeloproliferative neoplasms, with survival rates being lowest in Eastern Europe.
      This is the first paper to present large-scale, European survival data for
      patients with myeloid malignancies using prognosis-based groupings of entities
      defined by the third revision of the International Classification of Diseases for
      Oncology/World Health Organization classifications. Poor survival in some parts
      of Europe, particularly for treatable diseases such as chronic myeloid leukemia,
      is of concern for hematologists and public health authorities.

PMID- 22983591
TI  - Mosaic segmental uniparental isodisomy and progressive clonal selection: a common
      mechanism of late onset beta-thalassemia major.
AB  - Genomic DNA of 3 patients, born as healthy carriers and developing a late-onset
      severe transfusion-dependent beta-thalassemia major was studied by high-density
      genome wide SNP array analysis. A mosaic loss of heterozygosity for almost the
      entire 11p was found, not attributable to deletions but involving mosaicism for
      segmental paternal isodisomy of 11p. Mitotic recombination leading to mosaic
      segmental uniparental isodisomy on chromosome 11p in multiple tissues has been
      described as a molecular disease mechanism for a subset of sporadic Beckwith
      Wiedemann syndrome cases. A similar mechanism also seems to be involved in
      causing late-onset disease in carriers of recessive mutations in other genes
      located in 11p, such as late-onset beta-thalassemia major and sickle cell
      disease. We suggest that the loss of maternally imprinted IGF-2 and H19 genes may
      account for the selective advantage of hematopoietic cells containing this
      segmental paternal isodisomy of 11p carrying the beta-thalassemia mutation.

PMID- 22983592
TI  - Targeting etoposide to acute myelogenous leukaemia cells using nanostructured
      lipid carriers coated with transferrin.
AB  - The aim of the present study was to evaluate the diverse properties of
      transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using
      three different fatty amines, including stearylamine (SA), dodecylamine (DA) and
      spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs
      were prepared by an emulsion-solvent evaporation method followed by probe
      sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage
      between the surface-exposed amino group of the fatty amine and the carboxyl group
      of the protein. The physical coating was performed in a Ringer-Hepes buffer
      medium. NLCs were characterized by their particle size, zeta potential,
      polydispersity index, drug entrapment percentage, drug release profiles and Tf
      coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia
      cells was studied by MTT assay, and their cellular uptake was studied by a flow
      cytometry method. SA-containing NLCs showed the lowest particle size, the highest
      zeta potential and the largest coupling efficiency values. The drug entrapment
      percentage and the zeta potential decreased after Tf coupling, but the average
      particle size increased. SP-containing formulations released their drug contents
      comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released
      moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced
      cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors
      resulted in a significantly higher cell survival rate for Tf-NLCs. The highest
      cytotoxic activity was observed in the chemically coupled SA-containing
      nanoparticles, with an IC(50) value of 15-fold lower than free etoposide.

PMID- 22983593
TI  - Intubation time required for tracheal intubation with low-dose rocuronium in
      children with and without atropine.
AB  - PURPOSE: The purpose of this study was to determine the intubation time needed to
      facilitate tracheal intubation (Time(EI)) with a low dose of rocuronium (0.3
      mg/kg) during propofol induction, and to determine whether this time was reduced
      by the administration of atropine. METHODS: Forty-six children, aged 3-10 years,
      were randomly assigned to receive either saline (control group) or atropine 10
      MUg/kg (atropine group). Anesthesia was induced with alfentanil 10 MUg/kg,
      propofol 2.5 mg/kg, and rocuronium 0.3 mg/kg. Each Time(EI) at which tracheal
      intubation was attempted was predetermined according to the up-and-down method.
      The values of Time(EI) that provided excellent intubation conditions in 50 and 95
      % of patients were defined as Time(EI)50 and Time(EI)95, respectively. RESULTS:
      Time(EI)50 +/- SD was 160 +/- 26.2 and 150 +/- 13.7 s in the control and atropine
      groups, respectively. Using isotonic regression, Time(EI)95 in the control and
      atropine groups was 199 s (95 % CI 198.8-200.7 s) and 171 s (95 % CI 171.3-172.1
      s), respectively. Time(EI)95 was significantly higher in the control group than
      in the atropine group (P < 0.001). HR was significantly higher in the atropine
      group than in the control group during the study period. CONCLUSIONS: This study
      demonstrated that the Time(EI)95 of a low dose of rocuronium (0.3 mg/kg) required
      for excellent tracheal intubation was 199 s during i.v. anesthesia induction
      using propofol and alfentanil in children. Also, i.v. atropine (10 MUg/kg) before
      anesthesia induction was able to reduce Time(EI)95 by 28 s.

PMID- 22983594
TI  - Biological self-assembly of injectable hydrogel as cell scaffold via specific
      nucleobase pairing.
AB  - A biological hydrogel was self-assembled via Watson-Crick base pairing of thymine
      and adenine from functionalized star poly(ethylene glycol). Our work should
      provide a novel methodology to generate robust injectable scaffolds with
      tailorable properties for biomedical applications.

PMID- 22983595
TI  - Strategies for strain improvement in Fusarium fujikuroi: overexpression and
      localization of key enzymes of the isoprenoid pathway and their impact on
      gibberellin biosynthesis.
AB  - The rice pathogen Fusarium fujikuroi is known to produce a wide range of
      secondary metabolites, such as the pigments bikaverin and fusarubins, the
      mycotoxins fusarins and fusaric acid, and the phytohormones gibberellic acids
      (GAs), which are applied as plant growth regulators in agri- and horticulture.
      The development of high-producing strains is a prerequisite for the efficient
      biotechnological production of GAs. In this work, we used different molecular
      approaches for strain improvement to directly affect expression of early
      isoprenoid genes as well as GA biosynthetic genes. Overexpression of the first GA
      pathway gene ggs2, encoding geranylgeranyl diphosphate synthase 2, or additional
      integration of ggs2 and cps/ks, the latter encoding the bifunctional ent
      copalyldiphosphate synthase/ent-kaurene synthase, revealed an enhanced production
      level of 150%. However, overexpression of hmgR and fppS, encoding the key enzymes
      of the mevalonate pathway, hydroxymethylglutaryl coenzyme A reductase, and
      farnesyldiphosphate synthase, resulted in a reduced production level probably due
      to a negative feedback regulation of HmgR. Subsequent deletion of the
      transmembrane domains of HmgR and overexpression of the remaining catalytic
      domain led to an increased GA content (250%). Using green fluorescent protein and
      mCherry fusion constructs, we localized Cps/Ks in the cytosol, Ggs2 in small
      point-like structures, which are not the peroxisomes, and HmgR at the
      endoplasmatic reticulum. In summary, it was shown for the first time that
      amplification or truncation of key enzymes of the isoprenoid and GA pathway
      results in elevated production levels (2.5-fold). Fluorescence microscopy
      revealed localization of the key enzymes in different compartments.

PMID- 22983596
TI  - Sweet-taste-suppressing compounds: current knowledge and perspectives of
      application.
AB  - Sweet-tasting compounds are recognized by a heterodimeric receptor composed of
      the taste receptor, type 1, members 2 (T1R2) and 3 (T1R3) located in the mouth.
      This receptor is also expressed in the gut where it is involved in intestinal
      absorption, metabolic regulation, and glucose homeostasis. These metabolic
      functions make the sweet taste receptor a potential novel therapeutic target for
      the treatment of obesity and related metabolic dysfunctions such as diabetes.
      Existing sweet taste inhibitors or blockers that are still in development would
      constitute promising therapeutic agents. In this review, we will summarize the
      current knowledge of sweet taste inhibitors, including a sweet-taste-suppressing
      protein named gurmarin, which is only active on rodent sweet taste receptors but
      not on that of humans. In addition, their potential applications as therapeutic
      tools are discussed.

PMID- 22983597
TI  - Effect of W-TiO2 composite to control microbiologically influenced corrosion on
      galvanized steel.
AB  - Microorganisms tend to colonize on solid metal/alloy surface in natural
      environment leading to loss of utility. Microbiologically influenced corrosion or
      biocorrosion usually increases the corrosion rate of steel articles due to the
      presence of bacteria that accelerates the anodic and/or cathodic corrosion
      reaction rate without any significant change in the corrosion mechanism. An
      attempt was made in the present study to protect hot-dip galvanized steel from
      such attack of biocorrosion by means of chemically modifying the zinc coating. W
      TiO2 composite was synthesized and incorporated into the zinc bath during the hot
      dipping process. The surface morphology and elemental composition of the hot-dip
      galvanized coupons were analyzed by scanning electron microscopy and energy
      dispersive X-ray spectroscopy. The antifouling characteristics of the coatings
      were analyzed in three different solutions including distilled water, seawater,
      and seawater containing biofilm scrapings under immersed conditions. Apart from
      electrochemical studies, the biocidal effect of the composite was evaluated by
      analyzing the extent of bacterial growth due to the presence and absence of the
      composite based on the analysis of total extracellular polymeric substance and
      total biomass using microtiter plate assay. The biofilm-forming bacteria formed
      on the surface of the coatings was cultured on Zobell Marine Agar plates and
      studied. The composite was found to be effective in controlling the growth of
      bacteria and formation of biofilm thereafter.

PMID- 22983598
TI  - Attributing intentions to random motion engages the posterior superior temporal
      sulcus.
AB  - The right posterior superior temporal sulcus (pSTS) is a neural region involved
      in assessing the goals and intentions underlying the motion of social agents.
      Recent research has identified visual cues, such as chasing, that trigger animacy
      detection and intention attribution. When readily available in a visual display,
      these cues reliably activate the pSTS. Here, using functional magnetic resonance
      imaging, we examined if attributing intentions to random motion would likewise
      engage the pSTS. Participants viewed displays of four moving circles and were
      instructed to search for chasing or mirror-correlated motion. On chasing trials,
      one circle chased another circle, invoking the percept of an intentional agent;
      while on correlated motion trials, one circle's motion was mirror reflected by
      another. On the remaining trials, all circles moved randomly. As expected, pSTS
      activation was greater when participants searched for chasing vs correlated
      motion when these cues were present in the displays. Of critical importance, pSTS
      activation was also greater when participants searched for chasing compared to
      mirror-correlated motion when the displays in both search conditions were
      statistically identical random motion. We conclude that pSTS activity associated
      with intention attribution can be invoked by top-down processes in the absence of
      reliable visual cues for intentionality. 

PMID- 22983599
TI  - The beta-barrel assembly machinery (BAM) is required for the assembly of a
      primitive S-layer protein in the ancient outer membrane of Thermus thermophilus.
AB  - The ancient bacterial lineage Thermus spp has a primitive form of outer membrane
      attached to the cell wall through SlpA, a protein that shows intermediate
      properties between S-layer proteins and outer membrane (OM) porins. In E. coli
      and related Proteobacteria, porins are secreted through the BAM (beta-barrel
      assembly machinery) pathway, whose main component is BamA. A homologue to this
      protein is encoded in all the Thermus spp so far sequenced, so we wondered if
      this pathway could be responsible for SlpA secretion in this ancient bacterial
      model. To analyse this hypothesis, we attempted to get mutants on this BamA(th)
      of T. thermophilus HB27. Knockout and deletion mutants lacking the last 10 amino
      acids were not viable, whereas its depletion by means of a BamA antisense RNA
      lead defective attachment to the cell wall of its OM-like envelope. Such defects
      were related to defective folding of the SlpA protein that was more sensitive to
      proteases than in a wild-type strain. A similar phenotype was found in mutants
      lacking the terminal Phe of SlpA. Further protein-protein interaction assays
      confirmed the existence of specific binding between SlpA and BamA(th). Taking
      together, these data suggest that SlpA is secreted through a BAM-like pathway in
      this ancestral bacterial lineage, supporting an ancient origin of this pathway
      before the evolution of the Proteobacteria.

PMID- 22983600
TI  - Work-related outcomes among female veterans and service members after treatment
      of posttraumatic stress disorder.
AB  - OBJECTIVE: This study examined the effect of treatment for posttraumatic stress
      disorder (PTSD) on work-related quality-of-life outcomes and the relationship
      between clinically significant change during treatment and work-related outcomes.
      Additional analyses explored whether current depression and employment status
      moderated the effects of treatment and clinically significant change. METHODS:
      Participants were 218 female veterans and soldiers with current PTSD who
      participated in a randomized clinical trial of treatment for PTSD. They received
      ten weekly sessions of prolonged exposure or present-centered therapy and were
      assessed before and after treatment and at three- and six-month follow-ups.
      Outcomes were clinician-rated and self-rated occupational impairment and self
      rated satisfaction with work. RESULTS: Both treatment groups had improvements in
      occupational impairment, and the degree of improvement by the two groups was
      similar. There was no pre- to posttreatment change in work satisfaction. At the
      end of treatment, participants who no longer met diagnostic criteria for PTSD had
      greater improvements in all domains of work-related quality of life than
      participants who still had PTSD. CONCLUSIONS: Although prolonged exposure
      resulted in better PTSD symptom outcomes than present-centered therapy in the
      randomized clinical trial, it did not result in better work-related quality-of
      life outcomes. The improvement in occupational impairment associated with loss of
      diagnosis suggests the importance of continuing treatment until clinically
      meaningful change has been attained.

PMID- 22983601
TI  - Characterization of a diffuse intrinsic pontine glioma cell line: implications
      for future investigations and treatment.
AB  - Diffuse intrinsic pontine gliomas arise almost exclusively in children, and
      despite advances in treatment, the majority of patients die within 2 years after
      initial diagnosis. Because of their infiltrative nature and anatomic location in
      an eloquent area of the brain, most pontine gliomas are treated without a
      surgical biopsy. The corresponding lack of tissue samples has resulted in a
      limited understanding of the underlying genetic and molecular biologic
      abnormalities associated with pontine gliomas, and is a substantial obstacle for
      the preclinical testing of targeted therapeutic agents for these tumors. We have
      established a human glioma cell line that originated from surgical biopsy
      performed on a patient with a pontine glioma. To insure sustainable in vitro
      propagation, tumor cells were modified with hTERT (human telomerase
      ribonucleoprotein reverse transcriptase), and with a luciferase reporter to
      enable non-invasive bioluminescence imaging. The hTERT modified cells are
      tumorigenic in athymic rodents, and produce brainstem tumors that recapitulate
      the infiltrative growth of brainstem gliomas in patients.

PMID- 22983603
TI  - Removal of Cr(VI) onto Ficus carica biosorbent from water.
AB  - The utilization of sustainable and biodegradable lignocellulosic fiber to
      detoxify the noxious Cr(VI) from wastewater is considered a versatile approach to
      clean up a contaminated aquatic environment. The aim of the present research is
      to assess the proficiency and mechanism of biosorption on Ficus carica bast fiber
      via isotherm models (Langmuir, Freundlich, Temkin, Harkin's-Jura, and Dubinin
      Radushkevich), kinetic models, and thermodynamic parameters. The biomass
      extracted from fig plant was characterized by scanning electron microscopy and
      Fourier-transform infrared spectroscopy. To optimize the maximum removal
      efficiency, different parameters like effect of initial concentration, effect of
      temperature, pH, and contact time were studied by batch method. The equilibrium
      data were best represented by the Langmuir isotherm model, and the maximum
      adsorption capacity of Cr(VI) onto biosorbent was found to be 19.68 mg/g. The
      pseudo-second-order kinetic model adequately described the kinetic data. The
      calculated values of thermodynamic parameters such as enthalpy change (?H(0)),
      entropy change (?S(0)), and free energy change (?G(0)) were 21.55 kJ/mol, 76.24
      J/mol K, and -1.55 kJ/mol, respectively, at 30  degrees C which accounted for
      spontaneous and endothermic processes. The study of adsorbent capacity for Cr(VI)
      removal in the presence of Na(+), Mg(2+), Ca(2+), SO 4 (2-) , HCO 3 (-) and Cl(-)
      illustrated that the removal of Cr(VI) increased in the presence of HCO(3-) ions;
      the presence of Na(+), SO 4 (2-) or Cl(-) showed no significant influence on
      Cr(VI) adsorption, while Ca(2+) and Mg(2+) ions led to an insignificant decrease
      in Cr(VI) adsorption. Further, the desorption studies illustrated that 31.10% of
      metal ions can be removed from an aqueous system, out of which 26.63% of metal
      ions can be recovered by desorption in first cycle and the adsorbent can be
      reused. The results of the scale-up study show that the ecofriendly
      detoxification of Cr(VI) from aqueous systems was technologically feasible.

PMID- 22983602
TI  - Overview of passive Chemcatcher sampling with SPE pretreatment suitable for the
      analysis of NPEOs and NPs.
AB  - The European Union Water Framework Directive (WFD; 2000/60/EC) is an important
      piece of environmental legislation that protects rivers, lakes, coastal waters
      and groundwaters (EC 2000). The implementation of the WFD requires the
      establishment and use of novel and low-cost monitoring programmes, and several
      methods, e.g. passive sampling, have been developed to make the sampling process
      more representative compared to spot sampling. This review considers passive
      sampling methods focusing mainly on a passive sampler named Chemcatcher(r), which
      has been used for monitoring several harmful compounds in aquatic environments.
      Also, the sample treatment and analysis of nonylphenol ethoxylates (NPEOs) and
      nonylphenol (NPs) from water using solid phase extraction (SPE) is briefly
      summarized. The procedure of Chemcatcher passive sampling is quite similar to
      that of the SPE extraction since it concentrates the studied compounds from water
      as well. After sampling, the accumulated substances are extracted from the
      receiving phase of the sampler. The concentrations of NPEOs and NPs are currently
      monitored by taking conventional spot samples; SPE can be successfully used as a
      pretreatment procedure. Chemcatcher(r) passive sampling technique is a simple and
      useful monitoring tool and can be applied to new chemicals, such as NPEOs and NPs
      in aquatic environments.

PMID- 22983604
TI  - In vitro Cr(VI) reduction by cell-free extracts of chromate-reducing bacteria
      isolated from tannery effluent irrigated soil.
AB  - Four efficient Cr(VI)-reducing bacterial strains were isolated from rhizospheric
      soil of plants irrigated with tannery effluent and investigated for in vitro
      Cr(VI) reduction. Based on 16S rRNA gene sequencing, the isolated strains SUCR44,
      SUCR140, SUCR186, and SUCR188 were identified as Bacillus sp. (JN674188),
      Microbacterium sp. (JN674183), Bacillus thuringiensis (JN674184), and Bacillus
      subtilis (JN674195), respectively. All four isolates could completely reduce
      Cr(VI) in culture media at 0.2 mM concentration within a period of 24-120 h;
      SUCR140 completely reduced Cr(VI) within 24 h. Assay with the permeabilized cells
      (treated with Triton X-100 and Tween 80) and cell-free assay demonstrated that
      the Cr(VI) reduction activity was mainly associated with the soluble fraction of
      cells. Considering the major amount of chromium being reduced within 24-48 h,
      these fractions could have been released extracellularly also during their
      growth. At the temperature optima of 28  degrees C and pH 7.0, the specific
      activity of Cr(VI) reduction was determined to be 0.32, 0.42, 0.34, and 0.28
      MUmol Cr(VI)min(-1)mg(-1) protein for isolates SUCR44, SUCR140, SUCR186, and
      SUCR188, respectively. Addition of 0.1 mM NADH enhanced the Cr(VI) reduction in
      the cell-free extracts of all four strains. The Cr(VI) reduction activity in cell
      free extracts of all the isolates was stable in presence of different metal ions
      tested except Hg(2+). Beside this, urea and thiourea also reduced the activity of
      chromate reduction to significant levels.

PMID- 22983605
TI  - Albumin prevents reactive oxygen species-induced mitochondrial damage, autophagy,
      and apoptosis during serum starvation.
AB  - Aberrant levels of reactive oxygen species (ROS) rapidly generated from NADPH
      oxidase (NOX) activation can be cytotoxic due to activating pro-apoptotic
      signals. However, ROS also induce pro-survival autophagy through the engulfment
      of damaged mitochondria. This study is aimed at investigating the cytoprotective
      role of albumin against NOX/ROS-induced autophagy and apoptosis under serum
      starvation. Serum starvation induced apoptosis following a myeloid cell leukemia
      sequence 1 (Mcl-1)/Bax imbalance, loss of the mitochondrial transmembrane
      potential, and caspase activation accompanied by pro-survival autophagy following
      canonical inhibition of mammalian target of rapamycin complex 1 (mTORC1).
      Aberrant ROS generation, initially occurring through NOX, facilitated
      mitochondrial damage, autophagy, and apoptosis. Autophagy additionally regulated
      the accumulation of ROS-generating mitochondria. NOX/ROS permitted p38 mitogen
      activated protein kinase (p38 MAPK)-regulated mitochondrial apoptosis,
      accompanied by non-canonical induction of autophagy. In addition, activation of
      glycogen synthase kinase (GSK)-3beta by NOX/ROS-inactivated Akt facilitated a
      decrease in Mcl-1, followed by mitochondrial apoptosis as well as autophagy.
      Restoring albumin conferred an anti-oxidative effect against serum starvation
      deregulated NOX, p38 MAPK, and Akt/GSK-3beta/Mcl-1/caspase-3 signaling. Albumin
      also prevented autophagy by sustaining mTORC1. These results indicate an anti
      oxidative role for albumin via preventing NOX/ROS-mediated mitochondrial
      signaling to stimulate apoptosis as well as autophagy. Autophagy, initially
      induced by canonical inhibition of mTORC1 and enhanced by non-canonical
      mitochondrial damage, acts physically as a pro-survival mechanism.

PMID- 22983606
TI  - Comparison of morphological and functional adaptations of the heart in highly
      trained triathletes and long-distance runners using cardiac magnetic resonance
      imaging.
AB  - "Athlete's heart" is characterized by an increase in ventricular chamber sizes
      and myocardial mass (MM), and is mainly observed in endurance athletes. At
      present, it remains unclear whether cardiac adaptations in long-distance runners
      differ from those in triathletes. Twenty male triathletes (mean age 38.7 +/- 6.2
      years) and 20 male marathon runners (mean age 44.1 +/- 7.9) underwent cardiac
      magnetic resonance imaging to calculate left and right ventricular end-diastolic
      volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction
      (EF), and MM. Late-enhancement (LE) imaging was used to exclude structural
      alterations or myocardial scarring. EDV, ESV, SV, and EF for the left and right
      ventricles, as well as MM, did not differ between long-distance runners and
      triathletes, although the weekly training volume was significantly higher in
      triathletes (17.05 vs 9.95 h/week, P < 0.0001). There was a significant
      correlation between weekly training volume and right and left EDV, right and left
      ESV as well as MM within the study group. Myocardial LE was absent in all
      athletes. Highly trained male long-distance runners and triathletes have
      comparable cardiac parameters. However, the extent of physical training seems to
      be associated with the degree of cardiac adaptation in endurance athletes. The
      absence of LE supports the idea that athlete's heart is a nonpathological
      adaptation of the cardiovascular system. 

PMID- 22983607
TI  - Depletion of homeodomain-interacting protein kinase 3 impairs insulin secretion
      and glucose tolerance in mice.
AB  - AIMS/HYPOTHESIS: Insufficient insulin secretion and reduced pancreatic beta cell
      mass are hallmarks of type 2 diabetes. Here, we focused on a family of serine
      threonine kinases known as homeodomain-interacting protein kinases (HIPKs). HIPKs
      are implicated in the modulation of Wnt signalling, which plays a crucial role in
      transcriptional activity, and in pancreas development and maintenance. The aim of
      the present study was to characterise the role of HIPKs in glucose metabolism.
      METHODS: We used RNA interference to characterise the role of HIPKs in regulating
      insulin secretion and transcription activity. We conducted RT-PCR and western
      blot analyses to analyse the expression and abundance of HIPK genes and proteins
      in the islets of high-fat diet-fed mice. Glucose-induced insulin secretion and
      beta cell proliferation were measured in islets from Hipk3 ( -/- ) mice, which
      have impaired glucose tolerance owing to an insulin secretion deficiency. The
      abundance of pancreatic duodenal homeobox (PDX)-1 and glycogen synthase kinase
      (GSK)-3beta phosphorylation in Hipk3 ( -/- ) islets was determined by
      immunohistology and western blot analyses. RESULTS: We found that HIPKs regulate
      insulin secretion and transcription activity. Hipk3 expression was most
      significantly increased in the islets of high-fat diet-fed mice. Furthermore,
      glucose-induced insulin secretion and beta cell proliferation were decreased in
      the islets of Hipk3 ( -/- ) mice. Levels of PDX1 and GSK-3beta phosphorylation
      were significantly decreased in Hipk3 ( -/- ) islets. CONCLUSIONS/INTERPRETATION:
      Depletion of HIPK3 impairs insulin secretion and glucose tolerance. Decreased
      levels of HIPK3 may play a substantial role in the pathogenesis of type 2
      diabetes.

PMID- 22983608
TI  - Reading disability and adult attained education and income: evidence from a 30
      year longitudinal study of a population-based sample.
AB  - This study examined the impact of childhood reading disability (RD) on adult
      educational attainment and income. Participants' (N = 1,344) RD was assessed at
      age 7, and adult educational attainment and income were assessed in midlife using
      categorical variables. Participants with RD at age 7 were 74% (95% CI: 0.18,
      0.37) less likely to attain a higher level of education and 56% (95% CI: 0.32,
      0.61) less likely to attain a higher level of income as an adult than
      participants with average or above reading achievement at age 7. Attained
      education was found to mediate the relationship between RD and attained income. 

PMID- 22983609
TI  - Wafer-scale MoS2 thin layers prepared by MoO3 sulfurization.
AB  - Atomically thin molybdenum disulfide (MoS(2)) layers have attracted great
      interest due to their direct-gap property and potential applications in
      optoelectronics and energy harvesting. Meanwhile, they are extremely bendable,
      promising for applications in flexible electronics. However, the synthetic
      approach to obtain large-area MoS(2) atomic thin layers is still lacking. Here we
      report that wafer-scale MoS(2) thin layers can be obtained using MoO(3) thin
      films as a starting material followed by a two-step thermal process, reduction of
      MoO(3) at 500  degrees C in hydrogen and sulfurization at 1000  degrees C in the
      presence of sulfur. Spectroscopic, optical and electrical characterizations
      reveal that these films are polycrystalline and with semiconductor properties.
      The obtained MoS(2) films are uniform in thickness and easily transferable to
      arbitrary substrates, which make such films suitable for flexible electronics or
      optoelectronics.

PMID- 22983610
TI  - Assessment of potential health risk for arsenic and heavy metals in some herbal
      flowers and their infusions consumed in China.
AB  - Herbal tea is consumed widely in China due to their therapeutic efficacy, mild
      features, and relatively low cost. To assess the health risk associated with
      drinking herbal tea, arsenic and seven heavy metals, namely Cu, Zn, Fe, Mn, Cd,
      Ni, and Pb in eight different types of herbal flowers and their infusions were
      determined by inductively coupled-mass spectrometry after microwave digestion.
      The accuracy and precision of the analytical method were confirmed by the
      certified reference material (GBW 07605). The results suggested that significant
      differences existed in all metal concentrations determined among different
      varieties of herbal flowers and their infusions. In general, the concentration of
      iron was higher than those of seven other metals in the investigated herbal
      flowers and their infusions. The hazard quotient (HQ) and hazard index (HI) were
      calculated to evaluate the noncarcinogenic health risk from individual metal and
      combined metals due to the dietary intakes via consumption of herbal infusions.
      Both the HQ and HI levels were far below one, suggesting that the dietary intakes
      of the eight metals determined from daily consumption 4.5 g of the investigated
      herbal flowers for a normal adult should pose no potential risk to human health.

PMID- 22983611
TI  - Monitoring of soil and groundwater contamination following a pipeline explosion
      and petroleum product spillage in Ijegun, Lagos Nigeria.
AB  - In May 2008, an accidental damage of a Nigerian National Petroleum Corporation
      (NNPC) pipeline occurred in Ijegun area of Lagos, Nigeria, resulting in oil
      spillage and consequent contamination of the environment. The residual
      concentration of the total hydrocarbon (THC) and benzene, toluene, ethylbenzene,
      and xylene (BTEX) in the groundwater and soil was therefore investigated between
      March 2009 and July 2010. Results showed elevated THC mean levels in groundwater
      which were above the World Health Organization maximum admissible value of 0.1
      mg/l. THC values as high as 757.97 mg/l in groundwater and 402.52 mg/l in soil
      were observed in March 2009. Pronounced seasonal variation in the concentration
      of THC in groundwater and soil samples show that there was significant (P < 0.05)
      difference in the measured concentration of THC between each season (dry and
      wet), with the highest being in the dry season and between the years 2009 and
      2010. Significant hydrocarbon contamination, 500 m beyond the explosion site and
      25 months after the incident, was observed revealing the extent of the spillage
      of petroleum products. The highest concentrations of 16.65 MUg/l (benzene), 2.08
      MUg/l (toluene), and 4864.79 MUg/l (xylene) were found in stations within the 100
      m buffer zone. Most of the samples of groundwater taken were above the target
      value of 0.2 MUg/l set for BTEX compounds by the Environmental Guidelines and
      Standards for Petroleum Industry in Nigeria. The level of hydrocarbon in the
      impacted area calls for concern and remediation of the area is urgently needed to
      reduce further negative impact on the ecosystem.

PMID- 22983612
TI  - Predicting copper concentrations in acid mine drainage: a comparative analysis of
      five machine learning techniques.
AB  - Acid mine drainage (AMD) is a global problem that may have serious human health
      and environmental implications. Laboratory and field tests are commonly used for
      predicting AMD, however, this is challenging since its formation varies from site
      to-site for a number of reasons. Furthermore, these tests are often conducted at
      small-scale over a short period of time. Subsequently, extrapolation of these
      results into large-scale setting of mine sites introduce huge uncertainties for
      decision-makers. This study presents machine learning techniques to develop
      models to predict AMD quality using historical monitoring data of a mine site.
      The machine learning techniques explored in this study include artificial neural
      networks (ANN), support vector machine with polynomial (SVM-Poly) and radial base
      function (SVM-RBF) kernels, model tree (M5P), and K-nearest neighbors (K-NN).
      Input variables (physico-chemical parameters) that influence drainage dynamics
      are identified and used to develop models to predict copper concentrations. For
      these selected techniques, the predictive accuracy and uncertainty were evaluated
      based on different statistical measures. The results showed that SVM-Poly
      performed best, followed by the SVM-RBF, ANN, M5P, and KNN techniques. Overall,
      this study demonstrates that the machine learning techniques are promising tools
      for predicting AMD quality.

PMID- 22983613
TI  - Application of DET (diffusive equilibrium in thin films) and DGT (diffusive
      gradients in thin films) techniques in the study of the mobility of sediment
      bound metals in the outer section of Songkhla Lake, Southern Thailand.
AB  - The techniques of diffusive equilibrium in thin films (DET) and diffusive
      gradients in thin films (DGT) were used in the outer section of Songkhla Lake,
      Thailand in order to obtain high-resolution profiles of total dissolved and
      labile trace metals in the sediment pore water and investigate benthic fluxes.
      Six DET probes and six DGT probes were deployed at the mouths of the Phawong,
      Samrong and U-Taphao canals. A close correspondence could be observed between the
      high-resolution profiles of Fe and As, revealing a close link between the
      reductive remobilization of Fe oxides and the reduction of As(V). Co and Ni DGT
      profiles showed a close correspondence with Mn, but a narrow mobilization zone.
      Reductive mobilization of Mn oxides and associated metals and sulfide
      precipitation control the behaviour of these metals. The DGT profiles of Cu, Zn,
      Cd and Pb show surface maximum, probably linked to organic matter degradation.
      Important benthic fluxes, especially for As, were found at the mouths of the U
      Taphao and Phawong canals.

PMID- 22983614
TI  - Polycyclic aromatic hydrocarbons in river sediments from the western and southern
      catchments of the Bohai Sea, China: toxicity assessment and source
      identification.
AB  - The concentration, distribution, and origin of 16 USEPA priority polycyclic
      aromatic hydrocarbons (PAHs) were investigated in river sediments from the
      western and southern catchments of the Bohai Sea, China. A toxicity assessment of
      28 sediment samples collected from 15 main rivers was conducted by utilizing
      threshold and probable effect concentrations (TEC and PEC, respectively) derived
      from consensus-based sediment quality guidelines. The concentrations of total
      PAHs (?PAH(16)) ranged from 0.14 to 10,757 MUg/kg dry weight (mean = 1,368.6
      MUg/kg). The high concentrations of PAHs found in Binhai New Area of Tianjin and
      Binzhou City are likely the result of rapid population and heavy industry growth,
      resulting in elevated point and nonpoint source inputs of PAHs. Of the samples
      collected, samples 1 and 10 (7.1 % of the total) were categorized as toxic since
      some of the PAH concentrations exceeded the corresponding PECs. Twenty samples
      were classified as nontoxic, with both the individual PAH and the ?PAH(16)
      concentrations falling below the corresponding TECs. Analyses of selected PAH
      isomer ratios aided in the identification of PAH origins, allowing for a
      discrimination between pyrogenic and petrogenic sources. Spatial variability
      confirmed source heterogeneity within the study area. The most significant PAH
      associated contamination was found in the Beitang River and Ji Canal, which are
      located in Binhai New Area. The magnitude of contamination and the likelihood of
      an ongoing influx of PAHs support the need for a better understanding of
      pollution sources and methods for both control and sediment restoration.

PMID- 22983615
TI  - Bioaccumulation of HCH isomers in selected macroinvertebrates from the Elbe
      River: sources and environmental implications.
AB  - Sediments of the Elbe River have been extremely polluted by contaminants
      originating from previous large-scale hexachlorocyclohexane (HCH) production and
      the application of gamma-HCH (lindane) in its catchment in the second half of the
      twentieth century. In order to gain knowledge on bioaccumulation processes at
      lower trophic levels, field investigations of HCHs in macroinvertebrates were
      carried out along the longitudinal profile of the Elbe and tributary. Among the
      sites studied, concentrations in macroinvertebrates ranged within five orders of
      magnitude (0.01-100 MUg/kg). In general, lower values of HCH isomers were
      observed at all Czech sites (mostly <1 MUg/kg) compared with those in Germany. At
      the most contaminated site, Spittelwasser brook (a tributary of the Mulde),
      extremely high concentrations were measured (up to 234 MUg/kg alpha-HCH and 587
      MUg/kg beta-HCH in Hydropsychidae). In contrast, the Obristvi site, though also
      influenced by HCH production facilities, showed only negligibly elevated values
      (mostly <1 MUg/kg). Results showed that fairly high levels of alpha-HCH and beta
      HCH compared to gamma-HCH can still be detected in aquatic environments of the
      Elbe catchment, and these concentrations are decreasing over time to a lesser
      extent than gamma-HCH. Higher HCH concentrations in sediments in the springtime
      are considered to be the result of erosion and transport processes during and
      after spring floods, and lower concentrations at sites downstream are thought to
      be caused by the time lapse involved in the transportation of contaminated
      particles from upstream. In addition, comparison with fish (bream) data from the
      literature revealed no increase in tissue concentrations between invertebrates
      and fish.

PMID- 22983616
TI  - Moderate and heavy metabolic stress interval training improve arterial stiffness
      and heart rate dynamics in humans.
AB  - Traditional continuous aerobic exercise training attenuates age-related increases
      of arterial stiffness, however, training studies have not determined whether
      metabolic stress impacts these favourable effects. Twenty untrained healthy
      participants (n = 11 heavy metabolic stress interval training, n = 9 moderate
      metabolic stress interval training) completed 6 weeks of moderate or heavy
      intensity interval training matched for total work and exercise duration. Carotid
      artery stiffness, blood pressure contour analysis, and linear and non-linear
      heart rate variability were assessed before and following training. Overall,
      carotid arterial stiffness was reduced (p < 0.01), but metabolic stress-specific
      alterations were not apparent. There was a trend for increased absolute high
      frequency (HF) power (p = 0.10) whereas both absolute low-frequency (LF) power (p
      = 0.05) and overall power (p = 0.02) were increased to a similar degree following
      both training programmes. Non-linear heart rate dynamics such as detrended
      fluctuation analysis [Formula: see text] also improved (p > 0.05). This study
      demonstrates the effectiveness of interval training at improving arterial
      stiffness and autonomic function, however, the metabolic stress was not a
      mediator of this effect. In addition, these changes were also independent of
      improvements in aerobic capacity, which were only induced by training that
      involved a high metabolic stress.

PMID- 22983617
TI  - The clinicopathologic characteristics of granulomatosis with polyangiitis
      (Wegener's): a retrospective study of 45 patients in Korea.
AB  - OBJECTIVES: The aim of this study was to determine the clinicopathologic
      characteristics of granulomatosis with polyangiitis (Wegener's) (GPA) in Korean
      patients. METHODS: The medical records of 45 patients with GPA treated in a
      single tertiary referral hospital were retrospectively analyzed with respect to
      clinical manifestations, including histology, ANCA positivity, disease stage, and
      disease activity. Patients were categorized into granulomatous, vasculitic, or
      mixed form based on an immunopathologic scoring system of granulomatous
      vasculitic activity. RESULTS: Thirty-one patients (68.9 %) showed ANCA positivity
      (C-ANCA/P-ANCA, 42.2 %/20.0 %, proteinase-3 (PR3) ANCA/myeloperoxidase (MPO)
      ANCA, 44.1 %/16.1 %), and these patients (female 48.4 %) were found to be
      associated with a higher frequency of renal involvement (51.6 vs. 7.1 %, p =
      0.004), elevated serum creatinine (29.0 vs. 0 %, p = 0.018), and higher mortality
      (29 vs. 7.1 %, p = 0.041) than ANCA-negative patients. Thirty-three patients
      (73.3 %, female 60.6 %) had the granulomatous form, whereas 8.9 and 17.8 % had
      the vasculitic and mixed forms, respectively. Patients with the granulomatous
      form were diagnosed earlier in their lives (mean age 51.2 vs. 62.3, p = 0.002)
      and had a lower frequency of renal involvement (21.2 vs. 100 %, p = 0.005)
      compared with those with the vasculitic form. Initial remission (69.7 vs. 25.0 %)
      and relapse (60.8 vs. 0 %) rates were higher for the granulomatous than for the
      vasculitic form. CONCLUSIONS: Taken together, in Korean patients with GPA, the
      granulomatous form was predominant and associated with a younger age at diagnosis
      and a lower frequency of renal involvement than the vasculitic form. ANCA
      positivity was found in 68.9 % and associated with renal involvement and higher
      mortality.

PMID- 22983618
TI  - Damage assessment in ANCA-associated vasculitis.
AB  - Antineutrophil cytoplasm antibody associated vasculitis has been transformed from
      life-threatening conditions to chronic relapsing long-term diseases as a result
      of significant advances in immunosuppressive therapy. Although mortality still
      occurs, it is much less frequent, with an average 5-year survival of over 70 %.
      In the setting of chronic conditions, it becomes increasingly important to
      monitor the burden of disease in terms of both active inflammation requiring
      immunosuppression and chronic damage (scarring) from vasculitis and its treatment
      and associated comorbidity. The damage that accumulates in patients with
      vasculitis does not respond to immunosuppressive treatment. It is important to
      distinguish disease activity from disease damage to prevent unnecessary
      immunosuppression, but it is equally important to recognize damage for what it
      is, so that it can be addressed appropriately. Damage is an inevitable
      consequence of long-term vasculitis for over 80 % of patients, which should not
      surprise us given the severity of the original illness. There is potential value
      in measuring damage as a means of providing prognostic information. Using a
      quantified score such as the Vasculitis Damage Index (VDI) allows us to predict
      mortality. Patients with at least five items of damage on the VDI score have
      substantially worse mortality (7- to 11-fold worse risk), as compared with those
      with lesser amounts of damage. These findings should be taken into context when
      planning the management of patients with vasculitis, as well as in clinical
      trials of vasculitis. Disease damage is an important surrogate for long-term
      outcome in vasculitis, and studies should be designed to limit the amount of
      damage accumulating as a result of therapeutic intervention, rather than simply
      controlling disease activity, as is currently the aim in recent randomized
      controlled trials in vasculitis. Furthermore, careful cataloguing of damage, as
      well as disease activity items, provides much greater detail in describing and
      observing the long-term natural history of primary systemic vasculitis in
      patients treated with immunosuppressive agents who survive their initial disease
      process.

PMID- 22983619
TI  - Endogenous content and release of [(3)H]-GABA and [(3)H]-glutamate in the spinal
      cord of chronically undernourished rat.
AB  - The aim of this study was to determine the effect of chronic undernutrition on
      the content and release of gamma-amino butyric acid (GABA) and glutamate (GLU)
      transmitters in the rat spinal cord. The release of [(3)H]-GABA and [(3)H]-GLU
      was determined by radioactive liquid scintillation techniques, and the
      concentrations of GABA and GLU in spinal cord preparations from control and
      undernourished young rats (50-60 days old) were measured by reverse-phase HPLC.
      The GABA and GLU contents in the lumbar spinal dorsal horn (L6 segment) were
      significantly lower in undernourished rats relative to control rats (22.2 +/- 3.7
      and 10.7 +/- 1.9 %, respectively; P < 0.05). Spinal cord blocks from
      undernourished animals also showed lower rates of [(3)H]-GABA and [(3)H]-GLU
      release than controls (27.6 +/- 3.5 and 12.8 +/- 2.5 %, respectively; P < 0.01).
      We propose that the decreases in GLU content and release are consistent with a
      reduced activation of either afferent fibers, spinal glutaminergic neurons, or
      both. Furthermore, we propose that the decreased content and release of GABA in
      undernourished animals are related to a depression in pre- and post-synaptic
      inhibition. In addition, we hypothesize that the reductions in GABA content and
      release serve as compensatory mechanisms to counterbalance decreases in sensory
      transmission and GLU content in the spinal cord of the chronically undernourished
      rat.

PMID- 22983621
TI  - ChIP-Seq and the complexity of bacterial transcriptional regulation.
AB  - Transcription factors (TFs) play a central role in regulating gene expression in
      all bacteria. Yet, until recently, studies of TF binding were limited to a small
      number of factors at a few genomic locations. Chromatin immunoprecipitation
      followed by sequencing enables mapping of binding sites for TFs in a global and
      high-throughput fashion. The NIAID funded TB systems biology project
      http://www.broadinstitute.org/annotation/tbsysbio/home.html aims to map the
      binding sites for every transcription factor in the genome of Mycobacterium
      tuberculosis (MTB), the causative agent of human TB. ChIP-Seq data already
      released through TBDB.org have provided new insight into the mechanisms of TB
      pathogenesis. But in addition, data from MTB are beginning to challenge many
      simplifying assumptions associated with gene regulation in all bacteria. In this
      chapter, we review the global aspects of TF binding in MTB and discuss the
      implications of these data for our understanding of bacterial gene regulation. We
      begin by reviewing the canonical model of bacterial transcriptional regulation
      using the lac operon as the standard paradigm. We then review the use of ChIP-Seq
      to map the binding sites of DNA-binding proteins and the application of this
      method to mapping TF binding sites in MTB. Finally, we discuss two aspects of the
      binding discovered by ChIP-Seq that were unexpected given the canonical model:
      the substantial binding outside the proximal promoter region and the large number
      of weak binding sites.

PMID- 22983620
TI  - Extracellular superoxide dismutase induced by dopamine in cultured astrocytes.
AB  - Under some pathological conditions in brain, a large amount of superoxide anion
      (O(2)(-)) is produced, causing various cellular damages. Among three isozymes of
      superoxide dismutase (SOD), extracellular (EC)-SOD should play a role to detoxify
      O(2)(-) in extracellular space; however, a little is known about EC-SOD in brain.
      Although dopamine (DA) stored in the synaptic vesicle is stable, the excess
      leaked DA is spontaneously oxidized to yield O(2)(-) and reactive DA quinones,
      causing damages of dopaminergic neurons. In the present study, we examined the
      effects of DA on SOD expression in cultured rat cortical astrocytes. By means of
      RT-PCR, all mRNA of three isozymes of SOD could be detected; however, only EC-SOD
      was increased by DA exposure for 24 h, dose-dependently. The expression of EC-SOD
      protein and the cell-surface SOD activity in astrocytes also increased with 100
      MUM DA exposure. The increase of EC-SOD mRNA by DA was inhibited by a DA
      transporter inhibitor, GBR12909, whereas it was not changed by DA receptor
      antagonists, SKF-83566 (D1) and haloperidol (D2). Furthermore, a monoamine
      oxidase inhibitor, pargyline, and antioxidants, N-acetyl-L-cysteine and
      glutathione, also did not affect the DA-induced expression of EC-SOD mRNA. On the
      other hand, an inhibitor of nuclear factor kappaB (NF-kappaB), ammonium
      pyrrolidine-1-carbodithioate, suppressed the DA-induced expression of EC-SOD
      mRNA. These results suggest that DA incorporated into the cells caused the
      induction of EC-SOD mRNA followed by the enhancements of EC-SOD protein level and
      the enzyme activity, and that NF-kappaB activation is involved in the mechanisms
      of the EC-SOD induction. The regulation of EC-SOD in astrocytes surrounding
      dopaminergic neurons may contribute to the defensive mechanism against oxidative
      stress in brain.

PMID- 22983622
TI  - Worry about cancer progression and low perceived social support: implications for
      quality of life among early-stage breast cancer patients.
AB  - BACKGROUND: Worry about cancer progression and perceived social support can
      affect cancer survivors' quality of life (QOL). METHODS: In 480 early-stage
      breast cancer survivors, we examined how worry about cancer progression and
      perceived social support 6 months after definitive surgery were associated with
      QOL (RAND 36-item Health Survey) at 6-, 12-, and 24-month follow-up. RESULTS: At
      6 months post-surgery, higher worry was associated with worse QOL for five of
      eight subscales. Lower social support was associated with worse QOL for four
      subscales. The negative effects of worry and limited social support dissipated
      for four subscales (worry) and two subscales (social support) by 12-month follow
      up and for all subscales by 24-month follow-up. Social support at 6 months
      moderated the relationship between T2 worry and T4 emotional well-being; post hoc
      tests did not clarify the nature of the interaction. CONCLUSION: Early-stage
      breast cancer survivors who worry about cancer progression and/or have low social
      support may experience lower levels of QOL that can take several months to
      resolve.

PMID- 22983623
TI  - It only gets better: a comment on Schlam et Al.

PMID- 22983624
TI  - Risk assessment of herbicides and booster biocides along estuarine continuums in
      the Bay of Vilaine area (Brittany, France).
AB  - A 2-year study was implemented to characterize the contamination of estuarine
      continuums in the Bay of Vilaine area (NW Atlantic Coast, Southern Brittany,
      France) by 30 pesticide and biocide active substances and metabolites. Among
      these, 11 triazines (ametryn, atrazine, desethylatrazine, desethylterbuthylazine,
      desisopropyl atrazine, Irgarol 1051, prometryn, propazine, simazine,
      terbuthylazine, and terbutryn), 10 phenylureas (chlortoluron, diuron, 1-(3,4
      dichlorophenyl)-3-methylurea, fenuron, isoproturon, 1-(4-isopropylphenyl)-3
      methylurea, 1-(4-isopropylphenyl)-urea, linuron, metoxuron, and monuron), and 4
      chloroacetanilides (acetochlor, alachlor, metolachlor, and metazachlor) were
      detected at least once. The objectives were to assess the corresponding risk for
      aquatic primary producers and to provide exposure information for connected
      studies on the responses of biological parameters in invertebrate sentinel
      species. The risk associated with contaminants was assessed using risk quotients
      based on the comparison of measured concentrations with original species
      sensitivity distribution-derived hazardous concentration values. For EU Water
      Framework Directive priority substances, results of monitoring were also compared
      with regulatory Environmental Quality Standards. The highest residue
      concentrations and risks for primary producers were recorded for diuron and
      Irgarol 1051 in Arzal reservoir, close to a marina. Diuron was present during
      almost the all survey periods, whereas Irgarol 1051 exhibited a clear seasonal
      pattern, with highest concentrations recorded in June and July. These results
      suggest that the use of antifouling biocides is responsible for a major part of
      the contamination of the lower part of the Vilaine River course for Irgarol 1051.
      For diuron, agricultural sources may also be involved. The presence of
      isoproturon and chloroacetanilide herbicides on some dates indicated a
      significant contribution of the use of plant protection products in agriculture
      to the contamination of Vilaine River. Concentration levels and associated risk
      were always lower in estuarine sites than in the reservoir, suggesting that Arzal
      dam reduces downstream transfer of contaminants and favors their degradation in
      the freshwater part of the estuary. Results of the additional monitoring of two
      tidal streams located downstream of Arzal dam suggested that, although some
      compounds may be transferred to the estuary, their impact was probably very low.
      Dilution by marine water associated with tidal current was also a major factor of
      concentration reduction. It is concluded that the highest risks associated to
      herbicides and booster biocides concerned the freshwater part of the estuary and
      that its brackish/saltwater part was exposed to a moderate risk, although some
      substances may sometimes exhibit high concentration but mainly at low tide and on
      an irregular basis.

PMID- 22983625
TI  - Identification of rice cultivar with exclusive characteristic to Cd using a field
      polluted soil and its foreground application.
AB  - Using low-accumulative plant, especially excluder crop, to safely produce food is
      one of the very important technologies of phytoremediation, which is practical to
      safe production and long-term remediation of heavy metal-contaminated soil. A pot
      experiment using field cadmium (Cd)-contaminated soil (Cd concentration was 0.75
      mg kg(-1)) was conducted to compare Cd accumulation differences among 39 normal
      rice cultivars (Japonica) in Shenyang region of China for food safety and high
      grain yield aim. The results showed that brown grain Cd concentration in 12 rice
      cultivars of a total of 39 tested cultivars was lower than 0.2 mg kg(-1)
      (Agricultural Trade Standard of Nonpollution Food for Rice of China, NY 5115
      2008). In these 12 cultivars, Cd enrichment factors (Cd concentration ratio in
      shoot to that in soil) of nine cultivars were lower than 1. Likewise, Cd
      translocation factors (Cd concentration ratio in shoot to that in root) of eight
      cultivars were lower than the 0.28 average. Furthermore, grain yield per pot of
      seven cultivars were higher than the average 18.4 g pot(-1). Four cultivars,
      i.e., Shendao 5, Tianfu 1, Fuhe 90, and Yanfeng 47 showed Cd-exclusive
      characteristic and better foreground application.

PMID- 22983626
TI  - X-shaped quasi-3D plasmonic nanostructure arrays for enhancing electric field and
      Raman scattering.
AB  - We propose and demonstrate strongly enhancing electric field and Raman scattering
      with a large tolerance to the light incident angle and polarization by using x
      shaped quasi-3D plasmonic nanostructure arrays (X-Q3D-PNAs). The finite
      difference time-domain simulations were used to study the reflectance spectra and
      electric field profiles of X-Q3D-PNAs. Results show that both surface plasmon
      polaritons and localized surface plasmon polaritons (LSPPs) can be generated at
      the metal/dielectric interfaces of the top gold thin film with square grating x
      shaped nanoholes. The resonance of the LSPPs generated at the gold islands formed
      between x-shaped nanoholes at the top gold thin film greatly enhance the electric
      fields at the tips of the cross-sectors of the x-shaped nanoholes. Both plasmon
      resonances and electric field enhancements are affected by the structural
      dimensions. The strong electric field enhancement and the large tolerance to the
      laser polarization were demonstrated by surface-enhanced Raman scattering
      experiments. This unique plasmonic property of X-Q3D-PNAs could be attractive for
      photovoltaics and biosensing applications.

PMID- 22983627
TI  - The effects of fungal root endophytes on plant growth: a meta-analysis.
AB  - Fungal root endophytes are plant associates that colonize root tissue internally
      without causing any obvious harm to their host. Although ubiquitous, this
      relationship is not well understood. Our objectives were to determine the effects
      of fungal root endophyte inoculation on plant biomass and nitrogen concentration
      by conducting an extensive meta-analysis. We also explored the effects of
      experimental conditions on the host-endophyte relationship. We performed analyses
      weighted with non-parametric variance on plant response to root endophytes from
      the Ascomycetes (excluding the Clavacipitaceae), including categorical analyses
      of 21 experimental factors, ranging from the identity of the host and the
      endophyte, to the composition of the growing medium. The response of total
      biomass to endophyte inoculation was 18% lower than non-inoculated controls,
      while individually, root biomass, shoot biomass, and nitrogen concentration
      responses to endophyte inoculation were neutral. The identities of both the host
      and the endophyte had an influence, as did the original source of the endophyte
      (whether or not the isolate used originated from the same host species).
      Experimental conditions also influenced the plant-endophyte relationship, with
      the most important being the availability and sources of carbon and organic
      nitrogen, particularly peat moss. Although our analysis demonstrates that overall
      plant biomass and nitrogen concentration responses to ascomycetous root endophyte
      inoculation is neutral to negative, these results are somewhat confounded by
      among-study differences in experimental conditions, which undoubtedly contribute
      to the high levels of variability in plant response seen in the literature.

PMID- 22983628
TI  - siRNA as a tool to delineate pathway channelization in H(2)O(2) induced apoptosis
      of primary Leydig cells in vitro.
AB  - Using siRNA as a tool, the channelization of pathway in H(2)O(2) induced
      apoptosis of primary Leydig cells was investigated in vitro. Exposure (4 h) to
      H(2)O(2) (250 MUM) induced maximum apoptosis but affected Leydig cell viability
      significantly. Therefore, expression of apoptotic marker genes, caspase-8, -9, -3
      and polyadenosine ribose polymerase was subsequently investigated using the same
      concentration post 1 h exposure. Incubation with siRNA (20 nM) either for caspase
      8 or -9, inhibited their individual expressions by 55-60 % and activity, 50-55 %.
      The inhibition efficiency using siRNA was comparable with post- or pre-H(2)O(2)
      treatment of cells. Like siRNA, Eugenia jambolana (100 MUg/ml) plant extract too,
      effectively countered over-expression of all apoptotic marker proteins. Silencing
      expressions of caspase 8 but not 9 through siRNA leads to a profound inhibition
      of caspase 3 implying that H(2)O(2) induced Leydig cell apoptosis is preferably
      channeled through extrinsic and later extending to other pathways.

PMID- 22983629
TI  - Cochrane review says telephone follow-up of heart failure patients is effective.

PMID- 22983630
TI  - University College London issues new research standards but says it won't
      investigate Wakefield.

PMID- 22983631
TI  - Deadline approaches to claim funding in England for continuing healthcare needs.

PMID- 22983632
TI  - Child mortality falls, but 19 000 under 5s still die every day.

PMID- 22983633
TI  - Congenital giant craniopharyngioma.
AB  - PURPOSE: Congenital intracranial tumors are extremely rare and the most common is
      teratoma. Craniopharyngioma is a rare neonatal tumor with only eight cases
      reported. The management of this tumor in the neonatal period is still
      controversial, with the best results obtained when radical resection is
      performed. We present the case of a patient who received the diagnosis of a
      suprasellar tumor during the prenatal period and reviewed literature regarding
      the management. METHODS: We report a case of neonatal craniopharyngioma treated
      surgically. RESULTS: The routine ultrasound at 29 weeks of gestation showed a
      suprasellar echogenic image measuring 44 mm in diameter with polyhydramnios and
      macrocephaly. The patient was born at 38 weeks of gestation and underwent a
      surgical treatment on its 32nd day of life and the excision of almost 80 % of the
      lesion was achieved. He developed a subdural hygroma and on the 51st day of life,
      a subduroperitoneal shunt was installed to treat it. This patient died at 8
      months of life due to complications of a shunt infection. CONCLUSION: The present
      case is the ninth diagnosed during the prenatal period and the literature is
      controversial on the management of this rare tumor. The complete excision of the
      lesion using the microsurgical technique is the gold standard treatment for these
      patients; however, there are many factors that limit this approach in neonates.
      Usually, the resected tumors were smaller than 6 cm. Tumors larger than 8 cm have
      a worse prognosis, with a short survival time.

PMID- 22983634
TI  - Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively
      activated M2 macrophages and ameliorates insulin resistance and fatty liver in
      lipoatrophic diabetic A-ZIP transgenic mice.
AB  - AIMS/HYPOTHESIS: Monocyte chemoattractant protein-1 (MCP-1)/chemokine (C-C motif)
      ligand (CCL) 2 (CCL2) secreted from white adipose tissue (WAT) in obesity has
      been reported to contribute to tissue macrophage accumulation and insulin
      resistance by inducing a chronic inflammatory state. MCP-1 has been shown to be
      elevated in the fatty liver of lipoatrophic A-ZIP-transgenic (A-ZIP-Tg) mice.
      Treatment of these mice with the CC chemokine receptor (CCR) 2 antagonist has
      been shown to ameliorate the hyperglycaemia, hyperinsulinaemia and hepatomegaly,
      in conjunction with reducing liver inflammation. However, since CCR2 antagonists
      can block not only MCP-1 but also MCP-2 (CCL8) and MCP-3 (CCL7), it remains
      unclear whether MCP-1 secreted from the liver could contribute to hyperglycaemia,
      hyperinsulinaemia and hepatomegaly in conjunction with liver inflammation, as
      well as to the M1 and M2 states of macrophage polarisation. METHODS: To address
      these issues, we analysed the effects of targeted disruption of MCP-1 in A-ZIP-Tg
      mice. RESULTS: MCP-1 deficiency alone or per se resulted in a significant
      amelioration of insulin resistance in A-ZIP-Tg mice, which was associated with a
      suppression of extracellular signal-regulated protein kinase (ERK)-1/2 and p38
      mitogen-activated protein kinase (p38MAPK) phosphorylation in liver. Although MCP
      1 deficiency did not reduce the expression of macrophage markers, it increased
      the expression of the genes encoding M2 macrophage markers such as Arg1 and
      Chi3l3, as well as significantly reducing the triacylglycerol content of livers
      from A-ZIP-Tg mice. CONCLUSIONS/ INTERPRETATION: Our data clearly indicated that
      MCP-1 deficiency improved insulin resistance and hepatic steatosis in A-ZIP-Tg
      mice and was associated with switching macrophage polarisation and suppressing
      ERK-1/2 and p38MAPK phosphorylation.

PMID- 22983635
TI  - Enterovirus-induced gene expression profile is critical for human pancreatic
      islet destruction.
AB  - AIMS/HYPOTHESIS: Virally induced inflammatory responses, beta cell destruction
      and release of beta cell autoantigens may lead to autoimmune reactions
      culminating in type 1 diabetes. Therefore, viral capability to induce beta cell
      death and the nature of virus-induced immune responses are among key determinants
      of diabetogenic viruses. We hypothesised that enterovirus infection induces a
      specific gene expression pattern that results in islet destruction and that such
      a host response pattern is not shared among all enterovirus infections but varies
      between virus strains. METHODS: The changes in global gene expression and
      secreted cytokine profiles induced by lytic or benign enterovirus infections were
      studied in primary human pancreatic islet using DNA microarrays and viral strains
      either isolated at the clinical onset of type 1 diabetes or capable of causing a
      diabetes-like condition in mice. RESULTS: The expression of pro-inflammatory
      cytokine genes (IL-1-alpha, IL-1-beta and TNF-alpha) that also mediate cytokine
      induced beta cell dysfunction correlated with the lytic potential of a virus.
      Temporally increasing gene expression levels of double-stranded RNA recognition
      receptors, antiviral molecules, cytokines and chemokines were detected for all
      studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also
      downregulated genes involved in glycolysis and insulin secretion.
      CONCLUSIONS/INTERPRETATION: The results suggest a distinct, virus-strain
      specific, gene expression pattern leading to pancreatic islet destruction and pro
      inflammatory effects after enterovirus infection. However, neither viral
      replication nor cytotoxic cytokine production alone are sufficient to induce
      necrotic cell death. More likely the combined effect of these and possibly
      cellular energy depletion lie behind the enterovirus-induced necrosis of islets.

PMID- 22983637
TI  - National trends in pediatric use of anticonvulsants.
AB  - OBJECTIVE: This research study aimed to assess national trends in pediatric use
      of anticonvulsants for seizures and psychiatric disorders. METHODS: In a cross
      sectional design, data from the National Ambulatory Medical Care Survey and the
      National Hospital Ambulatory Medical Care Survey were analyzed. Outpatient visit
      information for youths (ages 0-17 years) was grouped by year for 1996-1997, 2000
      2001, 2004-2005, and 2008-2009. Six of the most common anticonvulsant drugs used
      for psychiatric conditions were examined. Psychiatric diagnoses and seizure or
      convulsion diagnoses were identified with ICD-9-CM codes. The primary outcome
      measure was percentage prevalence of visits for anticonvulsants that included a
      psychiatric diagnosis as a proportion of total youth visits for an
      anticonvulsant. Total, diagnosis-stratified, and drug-specific visits, as well as
      visits for concomitant anticonvulsants and psychotropics, were analyzed. RESULTS:
      As a proportion of total youth visits for anticonvulsants, visits with a
      psychiatric diagnosis increased 1.7 fold (p<.001), whereas the proportion of
      seizure-related visits did not change significantly. Regardless of diagnosis,
      anticonvulsant use significantly increased, from .33% to .68% of total youth
      visits in the 14-year period. There were significant increases in anticonvulsant
      use to treat pediatric bipolar disorder and disruptive behavior disorders. Visits
      noting divalproex decreased while visits noting lamotrigine increased among
      visits involving a psychiatric diagnosis. The concomitant use of stimulants and
      anticonvulsants significantly increased in visits noting a psychiatric diagnosis.
      CONCLUSIONS: Whereas anticonvulsant use for seizure disorders across the 14-year
      period was stable, the use of these drugs for psychiatric conditions rose to a
      dominant position. The growth of concomitant and off-label use to treat
      behavioral disorders raises questions about effectiveness and safety in community
      populations of youths.

PMID- 22983636
TI  - Association between dietary meat consumption and incident type 2 diabetes: the
      EPIC-InterAct study.
AB  - AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk
      of type 2 diabetes. The present study aims to investigate the association between
      meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large
      prospective case-cohort study nested within the European Prospective
      Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years
      of follow-up, 12,403 incident cases of type 2 diabetes were identified among
      340,234 adults from eight European countries. A centre-stratified random
      subsample of 16,835 individuals was selected in order to perform a case-cohort
      design. Prentice-weighted Cox regression analyses were used to estimate HR and
      95% CI for incident diabetes according to meat consumption. RESULTS: Overall,
      multivariate analyses showed significant positive associations with incident type
      2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08;
      95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR
      1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron
      intake. Effect modifications by sex and class of BMI were observed. In men, the
      results of the overall analyses were confirmed. In women, the association with
      total and red meat persisted, although attenuated, while an association with
      poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations
      were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This
      prospective study confirms a positive association between high consumption of
      total and red meat and incident type 2 diabetes in a large cohort of European
      adults.

PMID- 22983639
TI  - Clinical practice guidelines (CPGs) reduce costs in the management of isolated
      splenic injuries at pediatric trauma centers.
AB  - PURPOSE: The American Pediatric Surgical Association Trauma Committee proposed
      the use of a clinical practice guideline (CPG) for the non-operative management
      of isolated splenic injuries in 1998. An analysis was conducted to determine the
      financial impact of CPGs on the management of these injuries. METHODS: The
      Pediatric Health Information System database, which contains data from 44
      children's hospitals, was used to identify children who sustained a graded
      isolated splenic injury between June 2005 and June 2010. Demographics, length of
      stay (LOS), readmission rates, and laboratory, imaging, procedural, and total
      cost data were determined for all hospitals verified as a pediatric trauma center
      by the American College of Surgeons and/or designated by their local authority.
      Comparisons were made between facilities self-identifying as having a splenic
      injury management CPG and those without a CPG. RESULTS: Children (1,154) with
      isolated splenic injuries (grades 1-4) were cared for in 26 pediatric trauma
      centers: 20 with a CPG and 6 without (non-CPG). Median costs were significantly
      lower at CPG than non-CPG centers for imaging (US $163 vs. US $641, P < .001),
      laboratory (US $629 vs. US $1,044, P < .001), and total hospital stay (US $9,868
      vs. US $10,830, P < .001). The median LOS for CPG and non-CPG centers were
      similar (3 vs. 2 days, P = .38), as were readmission rates within 90 days (3.1
      vs. 5.1 %, P = .21). Multiple linear regression indicated that LOS (P < .001) and
      utilization of a CPG (P = .007) are significant independent predictors of total
      cost. CONCLUSIONS: Utilization of a CPG to manage children with isolated splenic
      injuries at a pediatric trauma center results in significantly reduced imaging,
      laboratory, and total hospital costs independent of patient age, gender, grade,
      and LOS.

PMID- 22983640
TI  - Tailoring groundwater quality monitoring to vulnerability: a GIS procedure for
      network design.
AB  - Monitoring networks aiming to assess the state of groundwater quality and detect
      or predict changes could increase in efficiency when fitted to vulnerability and
      pollution risk assessment. The main purpose of this paper is to describe a
      methodology aiming at integrating aquifers vulnerability and actual levels of
      groundwater pollution in the monitoring network design. In this study carried out
      in a pilot area in central Italy, several factors such as hydrogeological
      setting, groundwater vulnerability, and natural and anthropogenic contamination
      levels were analyzed and used in designing a network tailored to the monitoring
      objectives, namely, surveying the evolution of groundwater quality relating to
      natural conditions as well as to polluting processes active in the area. Due to
      the absence of an aquifer vulnerability map for the whole area, a proxi
      evaluation of it was performed through a geographic information system (GIS)
      methodology, leading to the so called "susceptibility to groundwater quality
      degradation". The latter was used as a basis for the network density assessment,
      while water points were ranked by several factors including discharge, actual
      contamination levels, maintenance conditions, and accessibility for periodical
      sampling in order to select the most appropriate to the network. Two different
      GIS procedures were implemented which combine vulnerability conditions and water
      points suitability, producing two slightly different networks of 50 monitoring
      points selected out of the 121 candidate wells and springs. The results are
      compared with a "manual" selection of the points. The applied GIS procedures
      resulted capable to select the requested number of water points from the initial
      set, evaluating the most confident ones and an appropriate density. Moreover, it
      is worth underlining that the second procedure (point distance analysis [PDA]) is
      technically faster and simpler to be performed than the first one (GRID + PDA).

PMID- 22983641
TI  - Calibration and verification of a dissolved oxygen management model for a highly
      polluted river with extreme flow variations in Pakistan.
AB  - A dissolved oxygen (DO) model is calibrated and verified for a highly polluted
      River Ravi with large flow variations. The model calibration is done under medium
      flow conditions (431.5 m(3)/s), whereas the model verification is done using the
      data collected during low flow conditions (52.6 m(3)/s). Biokinetic rate
      coefficients for carbonaceous biochemical oxygen demand (CBOD) and nitrogenous
      biochemical oxygen demand (NBOD) (i.e, K(cr) and K(n)) are determined through the
      measured CBOD and ammonia river profiles. The calculated values of K cr and K n
      are 0.36 day(-1) and 0.34 day(-1), respectively. The close agreement between the
      DO model results and the field values shows that the verified model can be used
      to develop DO management strategies for the River Ravi. The biokinetic
      coefficients are known to vary with degree of treatment (DOT) and therefore need
      to be adjusted for a rational water quality management model. The effect of this
      variation on level of treatment has been evaluated by using the verified model to
      attain a DO standard of 4 mg/L in the river using the biokinetic rate
      coefficients as determined during the model calibration and verification process.
      The required DOT in this case is found to be 96 %, whereas the DOT is 86 % if
      adjusted biokinetic rate coefficients are used to reflect the effect of
      wastewater treatment. The cost of wastewater treatment is known to increase
      exponentially as the removal efficiency increases; therefore, the use of
      appropriate biokinetic coefficients to manage the water quality in rivers is
      important.

PMID- 22983642
TI  - Pseudo-pseudo Meigs' syndrome in a patient with systemic lupus erythematosus.
AB  - Pseudo-pseudo Meigs' syndrome (PPMS) is a rare manifestation of patients with
      systemic lupus erythematosus (SLE), defined by the presence of ascites, pleural
      effusions and an elevated CA-125 level. We describe a patient with longstanding
      lupus who presented with localized lymphadenopathy and subsequently developed
      massive chylous ascites with marked hypoalbuminemia. A brief historical overview
      of Meigs' syndrome and related entities is presented, along with a discussion of
      the differential diagnosis of hypoalbuminemia and ascites in an SLE patient. In
      addition, we speculate on the optimal therapeutic intervention in such a patient.

PMID- 22983643
TI  - Insights into the role of polymer-surfactant complexes in drug
      solubilisation/stabilisation during drug release from solid dispersions.
AB  - PURPOSE: To evaluate the role of polymer-surfactant interactions in drug
      solubilisation/stabilisation during the dissolution of spray-dried solid
      dispersions and their potential impact on in vivo drug solubilisation and
      absorption. METHODS: Dissolution/precipitation tests were performed on spray
      dried HPMC-Etravirine solid dispersions to demonstrate the impact of different
      surfactants on the in vitro performance of the solid dispersions. Interactions
      between HPMC and bio-relevant and model anionic surfactants (bile salts and SDS
      respectively) were further characterised using surface tension measurements,
      fluorescence spectroscopy, DLS and SANS. RESULTS: Fast and complete dissolution
      was observed in media containing anionic surfactants with no drug
      recrystallisation within 4 h. The CMCs of bile salts and SDS were dramatically
      reduced to lower CACs in the presence of HPMC and Etravirine. The maximum
      increases of the apparent solubility of Etravirine were with the presence of HPMC
      and SDS/bile salts. The SANS and DLS results indicated the formation of HPMC
      SDS/bile salts complexes which encapsulated/solubilised the drug. CONCLUSIONS:
      This study has demonstrated the impact HPMC-anionic surfactant interactions have
      during the dissolution of non-ionic hydrophilic polymer based solid dispersions
      and has highlighted the potential relevance of this to a fuller understanding of
      drug solubilisation/stabilisation in vivo.

PMID- 22983644
TI  - Effect of PEGylation on biodistribution and gene silencing of siRNA/lipid
      nanoparticle complexes.
AB  - PURPOSE: To determine the influence of physicochemical properties of lipid
      nanoparticles (LNPs) carrying siRNA on their gene silencing in vivo. Mechanistic
      understanding of how the architecture of the nanoparticle can alter gene
      expression has also been studied. METHODS: The effect of 3-N-[(omega
      methoxypoly(ethylene glycol)2000)carbamoyl]-1,2-dimyristyloxy-propylamine (PEG-C
      DMA) on hepatic distribution and FVII gene silencing was determined. FVII mRNA in
      hepatocytes and liver tissues was determined by Q-PCR. Hepatic distribution was
      quantified by FACS analysis using Cy5 labeled siRNA. RESULTS: Gene silencing was
      highly dependent on the amount of PEG-C-DMA present. FVII gene silencing
      inversely correlated to the amount of PEG-C-DMA in LNPs. High FVII gene silencing
      was obtained in vitro and in vivo when the molar ratio of PEG-C-DMA to lipid was
      0.5 mol%. Surprisingly, PEGylation didn't alter the hepatic distribution of the
      LNPs at 5 h post administration. Instead the amount of PEG present in the LNPs
      has an effect on red blood cell disruption at low pH. CONCLUSION: Low but
      sufficient PEG-C-DMA amount in LNPs plays an important role for efficient FVII
      gene silencing in vivo. PEGylation did not alter the hepatic distribution of
      LNPs, but altered gene silencing efficacy by potentially reducing endosomal
      disruption.

PMID- 22983645
TI  - Development of meloxicam salts with improved dissolution and pharmacokinetic
      behaviors in rats with impaired gastric motility.
AB  - PURPOSE: Because of its poor solubility in acidic solution, oral absorption and
      efficacy of meloxicam (MEL) may be reduced in severe pain patients with impaired
      gastric motility. The present study aimed to develop salt forms to overcome these
      drawbacks. METHOD: Upon MEL salt screening with eight counterions, five MEL salts
      were obtained. The physicochemical properties of these MEL salts were
      characterized with a focus on morphology, crystallinity, thermal behavior,
      dissolution, and chemical/photo-stability. Pharmacokinetic profiling of an orally
      administered MEL salt was also carried out in both normal rats and rats treated
      with propantheline for the suppression of gastric motility. RESULTS: Dissolution
      behaviors for all obtained MEL salts were markedly better than that of
      crystalline MEL; in particular, the initial dissolution rate of arginine MEL
      dihydrate (MEL/Arg) was ca. 14-fold higher than that of crystalline MEL. MEL/Arg
      was found to be chemically and physically stable. There was ca. 18-fold reduction
      of AUC(0-4) for orally dosed crystalline MEL (1.0 mg-MEL/kg) in propantheline
      treated rats compared with that in normal rats. In contrast, there was only a ca.
      3-fold difference in AUC(0-4) between normal and propantheline-treated rats after
      oral administration of MEL/Arg (1.0 mg-MEL/kg). CONCLUSION: From these findings,
      MEL/Arg may provide improved oral absorption in severe pain patients.

PMID- 22983646
TI  - Sequential monitoring of serum IL-6, TNF-alpha, and IFN-gamma levels in a CAEBV
      patient treated by plasma exchange and immunochemotherapy.
AB  - We report the case of a female patient with chronic active Epstein-Barr virus
      infection (CAEBV) accompanied by hemophagocytic syndrome (HPS). On admission, she
      presented with severe liver dysfunction and disseminated intravascular
      coagulation with elevation of serum IL-6, TNF-alpha, and IFN-gamma levels. Plasma
      exchange (PE) followed by immunochemotherapy with prednisolone, cyclosporine A,
      and VP16 was performed. PE decreased serum cytokine levels dramatically and
      improved liver function. Following immunochemotherapy, CAEBV became inactive.
      Four months after discharge, however, CAEBV relapsed with HPS, and serum cytokine
      levels were extremely elevated again. There was no response to
      immunochemotherapy, and the patient died 1 day after admission. We examined the
      cytokines in five additional untreated-CAEBV patients and determined that they
      were elevated above the normal level in all patients. These results suggest that
      inflammatory cytokines may have roles in the development of CAEBV, and that their
      depletion can be an effective treatment for this disease.

PMID- 22983647
TI  - Acquired ichthyosis as a presenting finding of Hodgkin's lymphoma.

PMID- 22983648
TI  - Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the
      treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type:
      13-year follow-up in 135 patients.
AB  - We conducted a retrospective study of 135 patients of stage IE/IIE extranodal
      natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction
      chemotherapy to find some valuable prognostic factors and analyze the usefulness
      of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in
      predicting prognosis. Most of the patients were in the low-risk group (IPI score
      0-1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 %
      of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10
      year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients
      with better performance status (ECOG 0-1), normal serum LDH level, without local
      invasiveness, low KPI scores, and IPI score of 0 had significantly better overall
      survival (P < 0.05) in univariate analysis. Using multivariate analysis, we
      identified serum LDH level, ECOG PS score and local invasiveness to be
      independent prognostic factors. In conclusion, ENKTL is an aggressive lymphoma
      that shows heterogeneity. The IPI and KPI score systems should be improved
      further to classify patients into different groups, and should be validated in
      larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL,
      CHOP is no longer the state of art and novel drugs should be incorporated into
      future treatments.

PMID- 22983649
TI  - Graphene nanoribbon-guided fluid channel: a fast transporter of nanofluids.
AB  - In this work, we present a conceptual design of nanofluid channels using graphene
      sheets as the container and nanoribbons as flow guiders. Using molecular dynamics
      simulations, we demonstrate that water molecules confined in such nanochannels
      can be well guided by the nanoribbons and form a regular shaped water stream. The
      viscosity of water transported along such nanochannels is found to be orders of
      magnitude lower than that of bulk water. Several unconventional structural and
      flow characteristics are revealed to be responsible for the fast transport
      phenomenon comparable to that in carbon nanotubes. The proposed nanoribbon-guided
      fluid channel is promising for use in next-generation integrated material systems
      for transporting fluids at high volumetric flow rates with considerably low
      driving forces.

PMID- 22983650
TI  - Minimally invasive double approach (anterior and posterior) to the lumbar spine
      in revision surgery.

PMID- 22983652
TI  - A DFT study on the initial stage of thermal degradation of Poly(methyl
      methacrylate)/carbon nanotube system.
AB  - DFT calculations, with VWN exchange correlation functional and double numeric
      basis set, were used to evaluate the energies required for the scission reactions
      taking place in the initial stage of the thermal degradation of Poly(methyl
      methacrylate) (PMMA) in the presence of a carbon nanotube (CNT). Side group and
      main chain scissions were investigated. The results averaged from five
      configurations of pure PMMA (DP=5) were used as references and compared to the
      results obtained for the five same configurations of PMMA grafted on three carbon
      nanotubes of similar diameter (1.49 nm). The bond dissociation energies (BDE) of
      main chain scission evaluated for grafted PMMA was 4 % less endothermic than for
      pure PMMA. These results seemed independent of the tested chirality (11,11);
      (12,10) and (16,5) of the carbon nanotubes. Comparisons with the BDE of the
      weakest bonds due to intrinsic defaults (head to head and unsaturated end chain)
      were performed.

PMID- 22983651
TI  - Epidemiological survey of ossification of the ligamentum flavum in thoracic
      spine: CT imaging observation of 993 cases.
AB  - OBJECTIVE: To investigate the characteristics of epidemiological distribution of
      the ossification of the ligamentum flavum (OLF) in the thoracic spine including
      the incidence, segmental distribution, and shape. METHODS: Chest spiral computed
      tomography scans of 993 cases (male 506, female 487, mean age 60 years, range 5
      102 years) who presented due to chest symptoms were analyzed with axial slices
      combined with sagittal slices. The conditions of OLF in the thoracic spine,
      including segments, thickness, location, and dural sac compression, were
      recorded. Prevalence was standardized according to the "Age Structure of
      Population in Beijing 2008". RESULTS: Among the population investigated, the
      standardized prevalence rate was 63.9 %. The standardized prevalence rate for
      males (68.5 %) was higher than that for females (59.0 %). The highest prevalence
      rate of OLF was in the 50-59 years age group (79.2 %); however, high density
      originated it can be found in individuals aged 10-19 years. The comparison of
      different thoracic segments showed that T10-11 (44.0 %) and T11-12 (41.6 %) had
      the highest prevalence rates. CONCLUSION: The prevalence of ossification of the
      ligamentum flavum was highest in the 50-59 years group, but also occurred in
      early years. OLF occurs more frequently in the lower than in the upper and middle
      thoracic regions and its prevalence increases with aging.

PMID- 22983653
TI  - Molecular docking and dynamics simulations of A.niger RNase from Aspergillus
      niger ATCC26550: for potential prevention of human cancer.
AB  - The aim of the present research was to study the anticancer effects of
      Aspergillus niger (A.niger) RNase. We found that RNase (A.niger RNase)
      significantly and dose dependently inhibited invasiveness of breast cancer cell
      line MDA MB 231 by 55 % (P<0.01) at 1 MUM concentration. At a concentration of 2
      MUM, the anti invasive effect of the enzyme increased to 90 % (P<0.002). Keeping
      the aim to determine molecular level interactions (molecular simulations and
      protein docking) of human actin with A.niger RNase we extended our work in-vitro
      to in-silico studies. To gain better relaxation and accurate arrangement of
      atoms, refinement was done on the human actin and A.niger RNase by energy
      minimization (EM) and molecular dynamics (MD) simulations using 43A(2) force
      field of Gromacs96 implemented in the Gromacs 4.0.5 package, finally the
      interaction energies were calculated by protein-protein docking using the HEX.
      These in vitro and in-silico structural studies prove the effective inhibition of
      actin activity by A.niger RNase in neoplastic cells and thereby provide new
      insights for the development of novel anti cancer drugs.

PMID- 22983654
TI  - Cyclo-hexa-peptides at the water/cyclohexane interface: a molecular dynamics
      simulation.
AB  - Molecular dynamic (MD) simulations have been performed to study the behaviors of
      ten kinds of cyclo-hexa-peptides (CHPs) composed of amino acids with the diverse
      hydrophilic/hydrophobic side chains at the water/cyclohexane interface. All the
      CHPs take the "horse-saddle" conformations at the interface and the
      hydrophilicity/hydrophobicity of the side chains influences the backbones'
      structural deformations. The orientations and distributions of the CHPs at the
      interface and the differences of interaction energies (DeltaDeltaE) between the
      CHPs and the two liquid phases have been determined. RDF analysis shows that the
      H-bonds were formed between the O(C) atoms of the CHPs' backbones and H(w) atoms
      of water molecules. N atoms of the CHPs' backbones formed the H-bonds or van der
      Waals interactions with the water solvent. It was found that there is a parallel
      relationship between DeltaDeltaE and the lateral diffusion coefficients (D ( xy
      )) of the CHPs at the interface. The movements of water molecules close to the
      interface are confined to some extent, indicating that the dynamics of the CHPs
      and interfacial water molecules are strongly coupled.

PMID- 22983655
TI  - Modeling agricultural nonpoint source pollution using a geographic information
      system approach.
AB  - Agricultural non-point source (NPS) pollution, primarily sediment and nutrients,
      is the leading source of water-quality impacts to surface waters in North
      America. The overall goal of this study was to develop geographic information
      system (GIS) protocols to facilitate the spatial and temporal modeling of changes
      in soils, hydrology, and land-cover change at the watershed scale. In the first
      part of this article, we describe the use of GIS to spatially integrate watershed
      scale data on soil erodibility, land use, and runoff for the assessment of
      potential source areas within an intensively agricultural watershed. The
      agricultural non-point source pollution (AGNPS) model was used in the Muddy
      Creek, Ontario, watershed to evaluate the effectiveness of management strategies
      in decreasing sediment and nutrient [phosphorus (P)] pollution. This analysis was
      accompanied by the measurement of water-quality parameters (dissolved oxygen, pH,
      hardness, alkalinity, and turbidity) as well as sediment and P loadings to the
      creek. Practices aimed at increasing year-round soil cover would be most
      effective in decreasing sediment and P losses in this watershed. In the second
      part of this article, we describe a method for characterizing land-cover change
      in a dynamic urban fringe watershed. The GIS method we developed for the
      Blackberry Creek, Illinois, watershed will allow us to better account for
      temporal changes in land use, specifically corn and soybean cover, on an annual
      basis and to improve on the modeling of watershed processes shown for the Muddy
      Creek watershed. Our model can be used at different levels of planning with
      minimal data preprocessing, easily accessible data, and adjustable output scales.

PMID- 22983658
TI  - Outcomes of a group intensive peer-support model of case management for supported
      housing.
AB  - OBJECTIVE: Community-based intensive case management may be more intense than
      necessary and may be socially isolating for persons living in supported housing.
      This study evaluated a group intensive peer-support (GIPS) model of case
      management that was implemented in a supported housing program for homeless
      veterans with a broad range of psychiatric,substance use, and general medical
      problems. Group meetings led by case managers are the default mode of case
      management support, and individual intensive case management is provided only
      when clinically necessary. METHODS: GIPS was implemented by the U.S. Department
      of Housing and Urban Development-Veterans Affairs Supportive Housing(HUD-VASH)
      program at one demonstration site in April 2010. The study used administrative
      data to compare outcomes, service delivery, and timing of housing acquisition
      among clients of the demonstration site one year before (N=102) and after (N=167)
      GIPS implementation and among clients of other HUD-VASH sites across the country
      before (N=9,659) and after (N=21,318) implementation of GIPS at the demonstration
      site. RESULTS: After adjustment for differences in baseline characteristics, the
      analyses found that GIPS implementation was associated with a greater increase in
      social integration ratings, a greater number of case manager services, and faster
      acquisition of Section 8 housing vouchers after program admission compared with
      outcomes at the same site before GIPS implementation and at the other sites
      before and after implementation. CONCLUSIONS: GIPS may be a viable service model
      of supported housing that represents a recovery-oriented approach that can be
      scaled up to address homelessness.

PMID- 22983656
TI  - Gastroprotective mechanisms of the chloroform and ethyl acetate phases of
      Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae).
AB  - Flavonoid-rich Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae)
      is a native plant of South America. This study evaluates the gastroprotective
      activity and possible mechanisms for both the chloroform (CHCl3P) and ethyl
      acetate phases (AcOEtP) obtained from aerial parts of the plant. The activity was
      investigated using acute models of gastric ulcer. Gastric secretion biochemical
      parameters were determined after pylorus ligature. The participation of
      cytoprotective factors such as mucus, nitric oxide (NO), sulfhydryl (SH) groups,
      prostaglandin E2 (PGE2), reduced glutathione (GSH), superoxide dismutase (SOD),
      glutathione peroxidase (GPx), glutathione reductase (GR), reduction of lipid
      peroxidation (malondialdehyde level), and polymorphonuclear infiltration
      (myeloperoxidase activity), was also investigated. CHCl3P (125, 250, and 500
      mg/kg) and AcOEtP (62.5, 125, and 250 mg/kg) showed significant gastroprotective
      activity, reducing the ulcerative index by 75, 83, 88% and 66, 66, 81% for
      ethanol; 67, 67, 56% and 56, 53, 58% for a non-steroidal anti-inflammatory drug
      (NSAID); and 74, 58, 59% and 64, 65, 61% for stress-induced gastric ulcer,
      respectively. CHCl3P (125 mg/kg) and AcOEtP (62.5 mg/kg) significantly reduced
      the ulcerative area by 78 and 83%, respectively, for the ischemia-reperfusion
      model. They also did not alter the biochemical parameters of gastric secretion,
      the GSH level or the activities of SOD, GPx or GR. They increased the quantity of
      gastric mucus, not dependent on NO, yet dependent on SH groups, and maintained
      PGE2 levels. The P. clematidea phases demonstrated gastroprotective activity
      related to cytoprotective factors.

PMID- 22983657
TI  - Gastroprotective activity of the ethanolic extract and hexane phase of Combretum
      duarteanum Cambess. (Combretaceae).
AB  - Combretum duarteanum Cambess. is found in South America, particularly in Bolivia,
      Paraguay, and Brazil. In Paraiba state (Brazil), the species usually occurs in
      the Caatinga biome. It is popularly known as mofumbo, cipiuba, or cipauba. This
      work aims to evaluate the gastroprotective activity and the cytoprotective
      mechanisms of the ethanolic extract (Cd-EtOHE) and hexane phase (Cd-HexP)
      obtained from the leaves of C. duarteanum. Doses at 62.5, 125, 250, and 500 mg/kg
      of Cd-EtOHE and Cd-HexP were tested in models of gastric ulcers induced by
      HCl/ethanol, absolute ethanol, stress, non-steroidal anti-inflammatory drugs, and
      pylorus ligation in male rats or mice. Cd-EtOHE and Cd-HexP significantly reduced
      gastric injuries induced in all models. Cd-EtOHE and Cd-HexP did not alter
      gastric juice parameters such as pH, [H(+)], or volume after pylorus ligation.
      Cytoprotective mechanisms of Cd-EtOHE and Cd-HexP in relation to mucus, nitric
      oxide (NO), and sulfhydryl (SH) groups were evaluated. Neither product increased
      the mucus, and they both showed dependence on NO and SH groups to prevent gastric
      ulcer. Both Cd-EtOHE and Cd-HexP demonstrated gastroprotective activity.

PMID- 22983659
TI  - Marked increase in serum KL-6 and surfactant protein D levels during the first 4
      weeks after treatment predicts poor prognosis in patients with active
      interstitial pneumonia associated with polymyositis/dermatomyositis.
AB  - OBJECTIVE: The aim of this study is to determine whether serum KL-6 and
      surfactant protein D (SP-D) levels predict the prognosis of patients with
      interstitial pneumonia (IP) in cases of polymyositis (PM) and dermatomyositis
      (DM). PATIENTS AND METHODS: Fifty consecutive patients with PM (n = 17) or DM (n
      = 33) and active IP, 6 of whom died of respiratory failure, were enrolled in this
      study. Serum KL-6 and SP-D levels were measured every 2-4 weeks. Medical records
      were reviewed retrospectively. Univariate analyses and multivariate analyses with
      a logistic regression model were conducted. RESULTS: Serum KL-6 and SP-D levels
      were elevated in patients with active IP. At the time of diagnosis of active IP,
      the serum KL-6 level was within the normal range in 28 % of patients and the SP-D
      level was within the normal range in 46 % of patients. Serum KL-6 level increased
      up to 3 months after starting treatment and then decreased gradually to baseline,
      whereas SP-D level peaked within the first 4 weeks after treatment and decreased
      rapidly to normal levels. Patients with poor prognosis showed increases in KL-6
      and SP-D levels during the first 4 weeks after treatment, which was confirmed by
      uni- and multivariate analyses. Comparing the marker levels at 2-4 weeks after
      treatment with those at 0 weeks, an increase in the ratio over 1.70 for KL-6 and
      over 1.75 for SP-D, and an increase in KL-6 over 850 U/ml during the first 4
      weeks after treatment, were poor prognostic factors. CONCLUSIONS: Increases in
      serum KL-6 and SP-D levels during the first 4 weeks after starting therapy, but
      not their levels at any one time point, predict poor prognosis in patients with
      PM/DM. When marked increases of KL-6 and SP-D levels during the first 4 weeks are
      found or are predicted by serial measurement of the markers, patients have risks
      of poor prognosis and additional therapy should be considered.

PMID- 22983660
TI  - Chemical composition of metapleural gland secretions of fungus-growing and non
      fungus-growing ants.
AB  - The metapleural gland is exclusive to ants, and unusual among exocrine glands in
      having no mechanism for closure and retention of secretion. As yet, no clear
      conclusion has been reached as to the function of metapleural gland secretion.
      Metapleural gland secretions were investigated for fungus-growing ants
      representing the derived attines Trachymyrmex fuscus, Atta laevigata, and
      Acromyrmex coronatus, the basal attines Apterostigma pilosum and Mycetarotes
      parallelus, and non-fungus-growing ants of the tribes Ectatommini (Ectatomma
      brunneum) and Myrmicini (Pogonomyrmex naegeli). Our results showed that the
      secretions of leaf-cutting ants (A. laevigata and A. coronatus) and the derived
      attine, T. fuscus, contain a greater variety and larger quantities of volatile
      compounds than those of myrmicine and ectatommine ants. The most abundant
      compounds found in the metapleural glands of A. laevigata and A. coronatus were
      hydroxyacids, and phenylacetic acid (only in A. laevigata). Indole was present in
      all groups examined, while skatole was found in large quantities only in attines.
      Ketones and aldehydes are present in the secretion of some attines. Esters are
      present in the metapleural gland secretion of all species examined, although
      mainly in A. laevigata, A. coronatus, and T. fuscus. Compared with basal attines
      and non-fungus-growing ants, the metapleural glands of leaf-cutting ants produce
      more acidic compounds that may have an antibiotic or antifungal function.

PMID- 22983661
TI  - Cardiac sarcoidosis: diagnosis and management.
AB  - OPINION STATEMENT: Cardiac sarcoidosis can be life threatening if not promptly
      diagnosed and treated appropriately and aggressively. The diagnosis of myocardial
      disease is often difficult and circumstantial because there are no reliable
      diagnostic tests. Except for the finding of noncaseating granulomas on
      endomyocardial biopsy, most tests are limited and nonspecific. Therefore, the
      decision of initiating treatment is based on the patient's symptoms and the
      course of the disease, rather than on the presence of histologic confirmation.
      The goal of therapy is to prevent irreversible cardiomyopathy and to thwart the
      progression to heart transplantation. The mainstay of treatment is
      corticosteroids, although there are no large randomized trials analyzing
      corticosteroid use. The combination with other immunosuppressant agents, such as
      Methotrexate and Azathioprine, is initiated on the patient's failing or
      experiencing severe side effects from corticosteroids. While there are small
      studies proving the efficacy of tumor necrosis factor-inhibitors in cardiac
      sarcoidosis, more experience with these agents is needed. Catheter ablation or
      placement of implantable devices is indicated prophylactically in patients with
      severe ventricular tachyarrhythmias. Heart transplantation should be considered
      in patients with severe heart failure refractory to medical therapy. This article
      focuses on the current diagnostic tests and treatment recommendations for cardiac
      sarcoidosis.

PMID- 22983662
TI  - Endocrine (plasma cortisol and glucose) and behavioral (locomotor and self
      feeding activity) circadian rhythms in Senegalese sole (Solea senegalensis Kaup
      1858) exposed to light/dark cycles or constant light.
AB  - The existence of daily rhythms under light/dark (LD) cycles in plasma cortisol,
      blood glucose and locomotor and self-feeding activities, as well as their
      persistence (circadian nature) under constant light (LL), was investigated in
      Senegalese sole (Solea senegalensis). For the cortisol and glucose rhythms study,
      48 soles were equally distributed in 8 tanks and exposed to a 12:12 LD cycle and
      natural water temperature (experiment 1). After an acclimation period, blood was
      sampled every 3 h until a 24-h cycle was completed. Blood glucose levels were
      measured immediately after sampling, while plasma cortisol was measured later by
      ELISA. In experiment 2, the fish were exposed to LL for 11 days, and after this
      period, the same sampling procedure was repeated. For the study of locomotor and
      self-feeding rhythms (experiment 3), two groups of sole were used: one exposed to
      LD and the other to LL. Each group was distributed within 3 tanks equipped with
      infrared photocells for the record of locomotor activity, and self-feeders for
      feeding behavior characterization. The results revealed a marked oscillation in
      cortisol concentrations during the daily cycle under LD, with a peak (35.65 +/-
      3.14 ng/ml) in the afternoon (15:00 h) and very low levels during the night (5.30
      +/- 1.09 ng/ml). This cortisol rhythm persisted under LL conditions, with lower
      values (mean cortisol concentration = 7.12 +/- 1.11 ng/ml) and with the peak
      shifted by 3 h. Both rhythms were confirmed by COSINOR analysis (p < 0.05). The
      synchronizing role of temperature and feeding schedule, in addition to light, is
      also discussed. Diel rhythms of glucose were not evident in LD or LL. As to
      locomotor and self-feeding activity, a very marked rhythm was observed under LD,
      with higher activity observed during the night, with acrophases located at 2:14
      and 3:37 h, respectively. The statistical significance of daily rhythms was
      confirmed by COSINOR analysis. Under LL, both feeding and locomotor rhythms
      persisted, with an endogenous period (tau) around 22.5 h. In short, our findings
      described for the first time the existence of circadian cortisol and behavioral
      circadian rhythms in flat fish. Such results revealed the importance of taking
      into account the time of day when assessing stress responses and evaluating
      physiological indicators of stress in fish.

PMID- 22983663
TI  - Sub-syndromal depression in adolescents attending primary care: frequency,
      clinical features and 6 months outcome.
AB  - BACKGROUND: The nature of adolescent sub-syndromal depression has not been
      investigated in primary care. AIMS: To document frequency, characteristics and 6
      month outcome of sub-syndromal depression amongst adolescent primary care
      attenders. METHOD: Primary care attenders (13-18 years) completed depression
      screening questionnaires (Mood and Feelings Questionnaires) at consultation and
      at 6 month follow-up. Those screening positive were interviewed with the K-SADS.
      Sub-syndromal depression was defined as high levels of depressive symptoms in the
      absence of depressive disorder. RESULTS: Two hundred and seventy four
      questionnaires were completed at consultation: the estimated rate of sub
      syndromal depression was 25 %. These young people were clinically intermediary
      between those without depressive symptoms and those with depressive disorder; at
      6-months follow-up 57 % had persistent depressive symptoms and 12 % had developed
      a depressive disorder. Negative life events during the follow-up period and a
      positive family history of depression were the strongest predictors of symptom
      persistence and the development of depressive disorder, respectively. CONCLUSION:
      Sub-syndromal depression is common and persistent, in adolescent primary care
      attenders and it deserves attention.

PMID- 22983664
TI  - Panic disorder among African Americans, Caribbean blacks and non-Hispanic whites.
AB  - INTRODUCTION: This study investigated co-morbidities, level of disability,
      service utilization and demographic correlates of panic disorder (PD) among
      African Americans, Caribbean blacks and non-Hispanic white Americans. METHODS:
      Data are from the National Survey of American Life (NSAL) and the National
      Comorbidity Survey-Replication (NCS-R). RESULTS: Non-Hispanic whites are the most
      likely to develop PD across the lifespan compared to the black subgroups.
      Caribbean blacks were found to experience higher levels of functional impairment.
      There were no gender differences found in prevalence of PD in Caribbean blacks,
      indicating that existing knowledge about who is at risk for developing PD
      (generally more prevalent in women) may not be true among this subpopulation.
      Furthermore, Caribbean blacks with PD were least likely to use mental health
      services compared to African Americans and non-Hispanic whites. CONCLUSION: This
      study demonstrates that PD may affect black ethnic subgroups differently, which
      has important implications for understanding the nature and etiology of the
      disorder.

PMID- 22983665
TI  - Sex differences in glucose and insulin trajectories prior to diabetes diagnosis:
      the Whitehall II study.
AB  - To examine sex differences in trajectories of glucose and insulin prior to the
      development of type 2 diabetes. Glucose and insulin levels from oral glucose
      tolerance tests performed every 5 years in the prospective Whitehall II cohort
      were analysed using mixed-effects models. Out of 6,712 White participants, 475
      men and 177 women developed diabetes during a median follow-up time of 14 years.
      Men who developed diabetes had higher fasting glucose levels than women over the
      entire follow-up period (P < 0.001), whereas trajectories of 2-h glucose did not
      differ between sexes (P = 0.34). Two-hour insulin levels tended to be higher
      among women than men developing diabetes (P = 0.05), but not after adjustment for
      height (P = 0.45). Men have higher fasting glucose levels than women many years
      before the diagnosis of diabetes and at time of diagnosis, indicating that the
      pathogenesis of diabetes may be different between sexes.

PMID- 22983666
TI  - Phylogenetic genomewide comparisons of the pentatricopeptide repeat gene family
      in indica and japonica rice.
AB  - More than 400 pentatricopeptide repeat (PPR) genes have been found in higher
      plants, but most of them have not been functionally analyzed and their origins
      are still obscure. In this study, we performed phylogenetic genomewide
      comparisons of the PPR gene family in indica and japonica rice to explore the
      expansion mechanisms of these genes in higher plants. The functions of PPR genes
      in plant CMS/Rf systems are also discussed. The results indicate that (1) unequal
      crossing over participated in the expansion of the newly evolved PPR genes in
      indica and japonica rice genomes, (2) CMS/Rf systems are different in monocots
      and dicots, (3) the BT-type CMS/Rf system exists in both indica and japonica
      rice, and (4) both the PPR gene family and the BT-type CMS/Rf system may have
      existed before the divergence of indica and japonica rice.

PMID- 22983669
TI  - Retraction. Belastungsmessungen nach der Miniplattenosteosynthese von
      Unterkieferwinkelfrakturen.

PMID- 22983667
TI  - Establishment and characterization of xenograft models of human neuroblastoma
      bone metastasis.
AB  - OBJECTS: To improve the therapy of advanced neuroblastoma (NB), it is critical to
      develop animal models that mimic NB bone metastases. Unlike the human disease, NB
      xenograft models rarely metastasize spontaneously to bone from the orthotopic
      site of primary tumor growth. METHODS: Single-cell suspensions of SY5Y, KCNR NB
      cells were injected directly into the femur of nude mice. Radiological and
      histological analyses and immunohistochemistry analyses were performed to
      characterize these osseous NB models. SY5Y and KCNR result in osteolytic
      responses. RESULTS: We have detected osteoprotegerin, receptor activator of
      nuclear factor kappa B ligand, parathyroid hormone-related protein, and
      endothelin-1, proteins associated with bone growth and osteolysis, and C-X-C
      chemokine receptor type 4 (CXCR4) involved in tumor growth and tumor cell
      migration in the NB cells grown in the bone. CONCLUSIONS: These animal models can
      be used to study biological interactions, pathways, and potential therapeutic
      targets and also to evaluate new agents for treatment and prevention of NB bone
      metastasis.

PMID- 22983670
TI  - Precise control of the size and noise of solid-state nanopores using high
      electric fields.
AB  - We present a methodology for preparing silicon nitride nanopores that provides in
      situ control of size with sub-nanometer precision while simultaneously reducing
      electrical noise by up to three orders of magnitude through the cyclic
      application of high electric fields in an aqueous environment. Over 90% of
      nanopores treated with this technique display desirable noise characteristics and
      readily exhibit translocation of double-stranded DNA molecules. Furthermore,
      previously used nanopores with degraded electrical properties can be rejuvenated
      and used for further single-molecule experiments.

PMID- 22983671
TI  - Cadmium inhibits the induction of high-affinity nitrate uptake in maize (Zea mays
      L.) roots.
AB  - Cadmium (Cd) detoxification involves glutathione and phytochelatins biosynthesis:
      the higher need of nitrogen should require increased nitrate (NO(3)(-)) uptake
      and metabolism. We investigated inducible high-affinity NO(3)(-) uptake across
      the plasma membrane (PM) in maize seedlings roots upon short exposure (10 min to
      24 h) to low Cd concentrations (0, 1 or 10 MUM): the activity and gene transcript
      abundance of high-affinity NO(3)(-) transporters, NO(3)(-) reductases and PM H(+)
      ATPases were analyzed. Exposure to 1 mM NO(3)(-) led to a peak in high-affinity
      (0.2 mM) NO(3)(-) uptake rate (induction), which was markedly lowered in Cd
      treated roots. Plasma membrane H(+)-ATPase activity was also strongly limited,
      while internal NO(3)(-) accumulation and NO(3)(-) reductase activity in extracts
      of Cd treated roots were only slightly lowered. Kinetics of high- and low
      affinity NO(3)(-) uptake showed that Cd rapidly (10 min) blocked the inducible
      high-affinity transport system; the constitutive high-affinity transport system
      appeared not vulnerable to Cd and the low-affinity transport system appeared to
      be less affected and only after a prolonged exposure (12 h). Cd-treatment also
      modified transcript levels of genes encoding high-affinity NO(3)(-) transporters
      (ZmNTR2.1, ZmNRT2.2), PM H(+)-ATPases (ZmMHA3, ZmMHA4) and NO(3)(-) reductases
      (ZmNR1, ZmNADH:NR). Despite an expectable increase in NO(3)(-) demand, a negative
      effect of Cd on NO(3)(-) nutrition is reported. Cd effect results in alterations
      at the physiological and transcriptional levels of NO(3)(-) uptake from the
      external solution and it is particularly severe on the inducible high-affinity
      anion transport system. Furthermore, Cd would limit the capacity of the plant to
      respond to changes in NO(3) (-) availability.

PMID- 22983672
TI  - Activity of the Arabidopsis RD29A and RD29B promoter elements in soybean under
      water stress.
AB  - The constitutive and drought-induced activities of the Arabidopsis thaliana RD29A
      and RD29B promoters were monitored in soybean (Glycine max (L.) Merr.] via
      fusions with the visual marker gene beta-glucuronidase (GUS). Physiological
      responses of soybean plants were monitored over 9 days of water deprivation under
      greenhouse conditions. Data were used to select appropriate time points to
      monitor the activities of the respective promoter elements. Qualitative and
      quantitative assays for GUS expression were conducted in root and leaf tissues,
      from plants under well-watered and dry-down conditions. Both RD29A and RD29B
      promoters were significantly activated in soybean plants subjected to dry-down
      conditions. However, a low level of constitutive promoter activity was also
      observed in both root and leaves of plants under well-watered conditions. GUS
      expression was notably higher in roots than in leaves. These observations suggest
      that the respective drought-responsive regulatory elements present in the RD29X
      promoters may be useful in controlling targeted transgenes to mitigate abiotic
      stress in soybean, provided the transgene under control of these promoters does
      not invoke agronomic penalties with leaky expression when no abiotic stress is
      imposed.

PMID- 22983673
TI  - Shoot to root communication is necessary to control the expression of iron
      acquisition genes in Strategy I plants.
AB  - Previous research showed that auxin, ethylene, and nitric oxide (NO) can activate
      the expression of iron (Fe)-acquisition genes in the roots of Strategy I plants
      grown with low levels of Fe, but not in plants grown with high levels of Fe.
      However, it is still an open question as to how Fe acts as an inhibitor and which
      pool of Fe (e.g., root, phloem, etc.) in the plant acts as the key regulator for
      gene expression control. To further clarify this, we studied the effect of the
      foliar application of Fe on the expression of Fe-acquisition genes in several
      Strategy I plants, including wild-type cultivars of Arabidopsis [Arabidopsis
      thaliana (L.) Heynh], pea [Pisum sativum L.], tomato [Solanum lycopersicon
      Mill.], and cucumber [Cucumis sativus L.], as well as mutants showing
      constitutive expression of Fe-acquisition genes when grown under Fe-sufficient
      conditions [Arabidopsis opt3-2 and frd3-3, pea dgl and brz, and tomato chln
      (chloronerva)]. The results showed that the foliar application of Fe blocked the
      expression of Fe-acquisition genes in the wild-type cultivars and in the frd3-3,
      brz, and chln mutants, but not in the opt3-2 and dgl mutants, probably affected
      in the transport of a Fe-related repressive signal in the phloem. Moreover, the
      addition of either ACC (ethylene precursor) or GSNO (NO donor) to Fe-deficient
      plants up-regulated the expression of Fe-acquisition genes, but this effect did
      not occur in Fe-deficient plants sprayed with foliar Fe, again suggesting the
      existence of a Fe-related repressive signal moving from leaves to roots.

PMID- 22983674
TI  - Therapeutic mammaplasty for breast cancer: oncological and aesthetic outcomes.
AB  - BACKGROUND: Therapeutic mammaplasty (TM) for breast cancer is a widely practiced
      oncoplastic technique. Patient selection criteria and method of margin assessment
      are not clearly established. The aim of our review was to analyse oncological and
      aesthetic outcomes over a 7 year period. METHODS: We conducted a retrospective
      review of 251 breast cancer patients who underwent TM from 2002 to 2009 at the
      Netcare Breast Care Centre, Johannesburg. Primary chemotherapy was used to
      downsize large tumours. Intraoperative margin assessment was performed.
      Statistical analysis was performed using Kaplan-Meier estimates. Cosmetic
      outcomes were assessed by an independent review panel using photographic
      material. RESULTS: Mean tumour size was 15.4 mm. Mean resection weight was 237 g.
      Sixty-four (25.5 %) patients received primary chemotherapy. Mean margin taken was
      15 mm. The back-to-theatre rate was 2 % (5 cases). A total of 222 patients
      underwent bilateral procedures. Contralateral occult disease was identified in
      six cases (2.4 %). The early (<2 months) complication rate was 3.2 %. Late
      complications were related to adjuvant radiotherapy (20.7 %). Mean follow-up was
      50 months. The recurrence rate was 4 %. Five of six patients with locoregional
      recurrence had DCIS at initial surgery. The mortality rate was 3.2 %. The overall
      survival rate was 96.4 % and the metastasis-free survival rate was 94.6 %.
      Acceptable aesthetic results were achieved in 96 % of the patients. CONCLUSIONS:
      Primary chemotherapy allowed for TM in patients with large tumours.
      Intraoperative margin assessment decreased reoperation rate. Contralateral
      matching procedures resulted in histological detection of occult disease. TM is
      an oncologically appropriate and cosmetically favourable technique.

PMID- 22983675
TI  - Microbial control of the cotton leafworm Spodoptera littoralis (Boisd.) by
      Egyptian Bacillus thuringiensis isolates.
AB  - Four local Bacillus thuringiensis (Bt) isolates that had been serologically
      identified as Bt var. kurstaki (Btk2, Btk3, and Btk66) and Bt var. mexicanensis
      (Btm27), in addition to two reference strains (4D20 and 4AC1), were laboratory
      assayed as microbial control agents against the Egyptian cotton leafworm
      Spodoptera littoralis (Boisd.). Polymerase chain reaction (PCR) amplification
      analysis revealed that each of the six experimental strains carries, at least, a
      cry1 type gene which expresses a protein toxin active against lepidopterous
      insects. Additionally, PCR amplification results demonstrated that 4D20 and Btk66
      contain the Lepidoptera- and Diptera-active cry2 type gene and that Btk66
      contains Coleoptera-active cry7 and cry8 genes. Among the six strains, Btk66 and
      Btm27 were the most promising microbial control agents against S. littoralis. The
      present findings were the first to report that Btm27 (classified as B.
      thuringiensis var. mexicanensis) is a very potent microbial control agent against
      S. littoralis-tested larvae. For more characterization of these two isolates, the
      sspO gene was investigated as a molecular chronometer. The DNA sequencing results
      proved that Btk66 and Btm27 carry sspO open reading frames with identical
      nucleotide sequences, suggesting a strong phylogenetic relationship between the
      two strains.

PMID- 22983676
TI  - Lumbar spine MRI in upright position for diagnosing acute and chronic low back
      pain: statistical analysis of morphological changes.
AB  - BACKGROUND: Patients with low back pain frequently demonstrate recumbent magnetic
      resonance imaging (MRI) alterations not always related to homogeneous clinical
      symptoms. The purpose of this study was to evaluate and quantify the statistical
      significance of variations of some anatomical parameters of the lumbosacral spine
      and reveal occult disc pathologies from recumbent to upright position in patients
      with acute and chronic low back pain. MATERIALS AND METHODS: Fifty-seven patients
      complaining of low back pain (27 women, 30 men) underwent dynamic lumbosacral MRI
      with a 0.25-T tilting system (G-scan Esaote). We settled five parameters for
      which variations have been evaluated: lumbosacral angle, lordosis angle, L3-L4
      intersomatic disc height, L3-L4 interspinous processes distance, and widest
      anteroposterior dural sac diameter. Images were obtained in both recumbent and
      upright positions. RESULTS: Statistically significant differences [one-way
      analysis of variance (ANOVA), p = 0.0043] were found between each pair of values
      of parameters sampled in recumbent and upright positions. In 70 % of patients, on
      visual qualitative analysis only, an increment of disc protrusions and/or
      spondylolisthesis was found in the upright position; in three cases, in the
      upright position only, an interarticular pseudocyst was found. CONCLUSIONS:
      Dynamic MRI with an open-configuration, low-field tilting MRI system is a
      feasible and promising tool to study degenerative pathology of the spine.
      Moreover, in cases of low back pain with negative MRI in the recumbent position
      or in patients with pain in the upright position only, tilting MRI permits
      visualization of occult spine and disc pathologies in patients with acute or
      chronic low back pain.

PMID- 22983677
TI  - Identification of high-risk communities for unattended out-of-hospital cardiac
      arrests using GIS.
AB  - Improving survival rates for out of hospital cardiac arrest (OHCA) at the
      neighborhood level is increasingly seen as priority in US cities. Since wide
      disparities exist in OHCA rates at the neighborhood level, it is necessary to
      locate neighborhoods where people are at elevated risk for cardiac arrest and
      target these for educational outreach and other mitigation strategies. This paper
      describes a GIS-based methodology that was used to identify communities with high
      risk for cardiac arrests in Franklin County, Ohio during the period 2004-2009.
      Prior work in this area used a single criterion, i.e., the density of OHCA
      events, to define the high-risk areas, and a single analytical technique, i.e.,
      kernel density analysis, to identify the high-risk communities. In this paper,
      two criteria are used to identify the high-risk communities, the rate of OHCA
      incidents and the level of bystander CPR participation. We also used Local
      Moran's I combined with traditional map overlay techniques to add robustness to
      the methodology for identifying high-risk communities for OHCA. Based on the
      criteria established for this study, we successfully identified several
      communities that were at higher risk for OHCA than neighboring communities. These
      communities had incidence rates of OHCA that were significantly higher than
      neighboring communities and bystander rates that were significantly lower than
      neighboring communities. Other risk factors for OHCA were also high in the
      selected communities. The methodology employed in this study provides for a
      measurement conceptualization of OHCA clusters that is much broader than what has
      been previously offered. It is also statistically reliable and can be easily
      executed using a GIS.

PMID- 22983678
TI  - Cross-species amplification of microsatellites reveals incongruence in the
      molecular variation and taxonomic limits of the Pilosocereus aurisetus group
      (Cactaceae).
AB  - The Pilosocereus aurisetus group contains eight cactus species restricted to
      xeric habitats in eastern and central Brazil that have an archipelago-like
      distribution. In this study, 5-11 microsatellite markers previously designed for
      Pilosocereus machrisii were evaluated for cross-amplification and polymorphisms
      in ten populations from six species of the P. aurisetus group. The genotypic
      information was subsequently used to investigate the genetic relationships
      between the individuals, populations, and species analyzed. Only the Pmac101
      locus failed to amplify in all of the six analyzed species, resulting in an 88 %
      success rate. The number of alleles per polymorphic locus ranged from 2 to 12,
      and the most successfully amplified loci showed at least one population with a
      larger number of alleles than were reported in the source species. The population
      relationships revealed clear genetic clustering in a neighbor-joining tree that
      was partially incongruent with the taxonomic limits between the P. aurisetus and
      P. machrisii species, a fact which parallels the problematic taxonomy of the P.
      aurisetus group. A Bayesian clustering analysis of the individual genotypes
      confirmed the observed taxonomic incongruence. These microsatellite markers
      provide a valuable resource for facilitating large-scale genetic studies on
      population structures, systematics and evolutionary history in this group.

PMID- 22983679
TI  - The role of rotational stimulation in vestibular compensation.

PMID- 22983680
TI  - A unified treatment of the reference estimation problem in depth EEG recordings.
AB  - The starting point of this paper is the analysis of the reference problem in
      intra-cerebral electroencephalographic (iEEG) recordings. It is well accepted
      that both surface and depth EEG signals are always recorded with respect to some
      unknown time-varying signal called reference. This article discusses different
      methods for determining and reducing the influence of the reference signal for
      the iEEG signals. In particular, we derive optimal approaches for the estimation
      of the reference signal in iEEG recording setups and demonstrate their relation
      to the well-known minimum power/variance distortionless response approaches
      derived for general array and antenna signal processing applications. We show
      that the proposed approaches achieve optimal performance in terms of estimation
      error and that they outperform other reference identification methods proposed in
      the literature. The developed algorithms are illustrated on simulated examples
      and on real iEEG signals.

PMID- 22983681
TI  - Psychophysiological effects of stress management in patients with atopic
      dermatitis: a randomized controlled trial.
AB  - Atopic dermatitis leads to, and can be triggered by, stress. Psychological
      interventions have been shown to have positive effects on skin status, itch and
      scratching behaviour. However, it has not been analysed whether stress management
      leads to a change in physiological stress level and psychophysiological stress
      reaction under acute stress in this patient group. In this study 28 patients with
      atopic dermatitis were randomized to an experimental group (cognitive behavioural
      stress management) or a control group. The endocrine stress level and skin status
      were measured before and after the stress management programme. A public-speaking
      paradigm was used to induce acute stress. The study revealed that the
      experimental group had a tentatively reduced cortisol awakening response after
      the stress management programme. In addition, the experimental group remained
      calmer and showed lower salivary cortisol levels under acute stress. Thus, stress
      management might be a useful addition to standard treatment in patients with
      atopic dermatitis.

PMID- 22983682
TI  - Treating metastatic disease: Which survival model is best suited for the clinic?
AB  - BACKGROUND: To avoid complications associated with under- or overtreatment of
      patients with skeletal metastases, doctors need accurate survival estimates.
      Unfortunately, prognostic models for patients with skeletal metastases of the
      extremities are lacking, and physician-based estimates are generally inaccurate.
      QUESTIONS/PURPOSES: We developed three types of prognostic models and compared
      them using calibration plots, receiver operating characteristic (ROC) curves, and
      decision curve analysis to determine which one is best suited for clinical use.
      METHODS: A training set consisted of 189 patients who underwent surgery for
      skeletal metastases. We created models designed to predict 3- and 12-month
      survival using three methods: an Artificial Neural Network (ANN), a Bayesian
      Belief Network (BBN), and logistic regression. We then performed crossvalidation
      and compared the models in three ways: calibration plots plotting predicted
      against actual risk; area under the ROC curve (AUC) to discriminate the
      probability that a patient who died has a higher predicted probability of death
      compared to a patient who did not die; and decision curve analysis to quantify
      the clinical consequences of over- or undertreatment. RESULTS: All models
      appeared to be well calibrated, with the exception of the BBN, which
      underestimated 3-month survival at lower probability estimates. The ANN models
      had the highest discrimination, with an AUC of 0.89 and 0.93, respectively, for
      the 3- and 12-month models. Decision analysis revealed all models could be used
      clinically, but the ANN models consistently resulted in the highest net benefit,
      outperforming the BBN and logistic regression models. CONCLUSIONS: Our
      observations suggest use of the ANN model to aid decisions about surgery would
      lead to better patient outcomes than other alternative approaches to decision
      making. LEVEL OF EVIDENCE: Level II, prognostic study. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 22983683
TI  - Two-stage treatment of hip periprosthetic joint infection is associated with a
      high rate of infection control but high mortality.
AB  - BACKGROUND: Periprosthetic infection after total hip arthroplasty (THA) is a
      devastating complication. Reported rates of infection control range from 80% to
      95% but mortality rates associated with treatment of infected THA are also
      substantial and we suspect underreported. QUESTIONS/PURPOSES: For patients
      selected for two-stage treatment of infected THA we therefore determined (1)
      mortality; (2) rate of reimplantation; and (3) rate of reinfection. METHODS: We
      identified 202 patients (205 hips) with infected primary or revision THA treated
      with a two-stage protocol between 1996 and 2009 in our prospectively collected
      practice registry. Patients underwent two-stage treatment for infection,
      including removal of all implants and foreign material with implantation of an
      antibiotic-laden cement spacer in the first stage followed by intravenous culture
      specific antibiotics for a minimum of 6 weeks. Second-stage reimplantation was
      performed if erythrocyte sedimentation rate and C-reactive protein were trending
      toward normal and the wound was well healed. Thirteen patients (13 hips) were
      lost to followup before 24 months. The minimum followup in surviving patients was
      24 months or failure (average, 53 months; range, 24-180 months). RESULTS:
      Fourteen patients (7%; 14 hips) died before reimplantation and two were not
      candidates because of medical comorbidities. The 90-day mortality rate after the
      first-stage debridement was 4% (eight patients). Of the 186 patients (189 hips)
      who underwent reimplantation, 157 (83%) achieved control of the infection.
      Including all patients who underwent the first stage, survival and infection
      control after two-stage reimplantation was 76%. CONCLUSION: Two-stage treatment
      of deep infection in primary and revision THA is associated with substantial
      mortality and a substantial failure rate from both reinfection and inability to
      perform the second stage. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 22983684
TI  - Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and
      Raf-1 in the liver of diabetic rats.
AB  - Selenium and exendin-4 exert antidiabetic effects by unknown mechanisms. Herein,
      we investigated their effects on the expression of glucagon-like peptide-1
      receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers
      of rats with streptozotocin-induced diabetes. Diabetic rats were injected
      intraperitoneally with exendin-4 (0.03 MUg/kg body weight) twice daily or treated
      with 5 ppm selenium as sodium selenite in drinking water for 4 weeks. Both
      selenium and exendin-4 reduced the hyperglycemia in diabetic rats. Induction of
      diabetes mellitus resulted in decreased level of GLP-1R and increased levels of
      IRS-1 and Raf-1 in the liver. Treatment of diabetic rats with selenium or exendin
      4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1
      in the liver, compared with the levels in diabetic rats. Therefore, the
      antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R,
      IRS-1, and Raf-1 levels in the liver.

PMID- 22983685
TI  - Polyphyletic origin of the genus Amaurornis inferred from molecular phylogenetic
      analysis of rails.

PMID- 22983686
TI  - Comprehensive analysis of UGT1A1 genetic polymorphisms in Chinese Tibetan and Han
      populations.
AB  - The study of polymorphism of the UGT1A1 gene has not been reported in the Chinese
      Tibetan population, and there are no comparisons of genetic polymorphism in the
      gene between Chinese Han and Tibetan populations. In this study, we directly
      sequenced the functional regions of the UGT1A1 gene in 200 unrelated healthy
      Chinese volunteers, detecting 20 variations (including five novel ones). The
      distributions of allele and genotype frequencies differ between the two groups.
      UGT1A1*6 is the major reduced functional variant in the populations, and the *27
      allele was detected only in the Han group. Differences in the frequencies of the
      UGT1A1*6/*63 genotype between the Tibetan and Han populations were statistically
      significant (P = 0.009). Our genetic data might provide fundamental information
      for the advance of personalized medicine and will facilitate genotype-phenotype
      studies in larger populations.

PMID- 22983687
TI  - Use of the LigaSure device and the Stapler for closure of the small bowel: a
      comparative ex vivo study.
AB  - PURPOSE: To evaluate the feasibility and effectiveness of the LigaSure device in
      closing divisions of the small bowel in an ex vivo porcine model. METHODS: Two
      types of closure were performed: stumps created by "muco-mucosa" fusion and
      stumps created by "sero-serosa" fusion. For each type of closure, different power
      levels of the LigaSure system were tested in combination with different numbers
      of applications and then compared with the Stapler group. RESULTS: With both
      types of intestinal closure, the highest value of burst pressure was obtained
      with the application of a power level of three bars and one frequency
      application. The high burst pressure of the muco-mucosa stump group was
      significantly lower than that of the Stapler group (41.8 +/- 5.9 vs. 75.8 +/-
      5.9, respectively, p < 0.01). No differences were found between the high burst
      pressure of the sero-serosa stump group and the Stapler group (74.1 +/- 5.5 vs.
      75.8 +/- 5.9, respectively, p = 0.2). CONCLUSIONS: Our preliminary results showed
      that the LigaSure is an efficient tool for closing the intestines when sero
      serosa stumps are created. The second step of our work will be to evaluate the
      feasibility of this tool in creating intestinal anastomoses.

PMID- 22983688
TI  - Effect of temperature on toxicity of deltamethrin and oxygen consumption by
      Porcellio scaber Latr (Isopoda).
AB  - This study describes the toxicity of deltamethrin, in relation to its LD50 value,
      as well as variation in respiratory metabolism of the isopod species Porcellio
      scaber Latr kept at 3 temperature values (10, 22 and 30oC). The low LD50 values
      obtained indicate that deltamethrin is a highly toxic pyrethroid for the
      crustacean tested, particularly at 10oC. We also observed that, in all the 3
      experimental temperatures, the deltamethrin toxicity was lower in females than in
      males. Particularly distinct differences between both sexes were visible at 10
      and 30oC, i.e. temperatures that are too low and too high for the species
      studied. Oxygen uptake measurement showed an increase in respiratory metabolism
      directly after intoxication. The most substantial increase, 64% in males and 80%
      in females, was observed at the temperature 10oC, whereas at the other
      temperatures, it did not exceed 20%. During the successive experimental days, the
      respiratory consumption in P. scaber had a tendency to decrease, which was more
      visible at 10 and 30oC, compared to the optimal temperature 22oC.

PMID- 22983689
TI  - The impact of sleep apnea treatment on carbohydrate metabolism in patients with
      acromegaly.
AB  - Sleep Apnea is highly prevalent and may contribute to insulin resistance in
      patients with acromegaly. The primary aim of this study was to assess the impact
      of sleep apnea treatment with a continuous positive air pressure (CPAP) device on
      insulin resistance evaluated by hyperinsulinemic euglycemic clamp (HEC). A
      prospective, randomized, open label, placebo-controlled, crossover study was
      performed at a tertiary outpatient pituitary center. Twelve acromegalic subjects
      on somatostatin analogs (SA) with a recent diagnosis of moderate to severe sleep
      apnea were randomized to CPAP therapy or to nasal dilator adhesive (NDA) with
      placebo effect for 3 months and then crossed over for another 3 months period
      without washout. Assessment of HEC, mathematical insulin resistance indexes
      (HOMA, HOMA2 and QUICKI), GH, IGF-1, HbA1c and free fat acids were performed. A
      significant reduction on insulin resistance was demonstrated by HEC at the end of
      the study in patients on CPAP (HEC, pre- and post-CPAP: 4.27 vs. 6.10 mg/Kg/min,
      P = 0.032). This reduction was not observed in NDA group (HEC, pre- and post
      adhesive: 5.53 vs. 5.19 mg/Kg/min, P = 0.455). There was no significant
      difference on HbA1c or on peripheral insulin resistance indexes in both
      treatments. CPAP promoted a significant increase on peripheral insulin
      sensitivity in acromegalic patients with moderate to severe sleep apnea on SA
      use. Our results support the concept that sleep apnea plays an important role on
      glucose metabolism. Insulin resistance indexes were unable to detect this
      finding.

PMID- 22983690
TI  - Acute administration of alprazolam, a benzodiazepine activating GABA receptors,
      inhibits cortisol secretion in patients with subclinical but not overt Cushing's
      syndrome.
AB  - The purpose of this study is to verify whether acute pre-treatment with
      alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal
      subjects, could better characterize patients with subclinical Cushing's syndrome
      (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with
      overt Cushing's syndrome (CS), 11 with non-functioning adrenal incidentalomas
      (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300
      hours) on cortisol levels after 1-mg DST. Cortisol levels (mean +/- SEM) after
      DST were lower (P = 0.012) in SCS (3.9 +/- 0.3 MUg/dl) than in overt CS (10.4 +/-
      1.9 MUg/dl), while they were higher (P = 0.0005) than in NF (1.1 +/- 0.1 MUg/dl)
      and NS (1.5 +/- 0.1 MUg/dl). After ALP pre-treatment, cortisol levels further
      decreased (P = 0.004) in SCS (3.0 +/- 0.3 MUg/dl), but neither in CS (9.3 +/- 1.3
      MUg/dl) nor in NF (1.3 +/- 0.1 MUg/dl) and in NS (1.3 +/- 0.1 MUg/dl). In SCS,
      cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in
      CS, but higher (P = 0.0005) than those in NF and NS. Considering individual
      cases, ALP pre-treatment reduced cortisol levels < 3 and < 1.8 MUg/dl in 50 and
      23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted
      by 1-mg DST in patients with SCS but not in those with CS. The clinical
      usefulness of ALP to increase the sensitivity of 1-mg DST to identify true
      autonomous cortisol release in patients with adrenal incidentalomas as well as to
      predict different clinical outcomes remains to be clarified.

PMID- 22983691
TI  - Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship
      to tumor behavior.
AB  - The aim of the study was to evaluate the presence of aromatase cytochrome P450
      enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of
      patients with prolactinoma and to examine the impact of the P450AROM expression
      on clinical outcome. Twenty-six consecutive human pituitary tissue samples were
      obtained from autopsies performed at the Institute of Forensic Medicine. Sixty
      four patients who had an adenomectomy between 2000 and 2009 after prolactinoma
      diagnosis with histologically confirmed pituitary tumor tissues were
      retrospectively included in this study. The slices from the pituitary tissues
      were subjected to immunohistochemical staining for evaluation of P450AROM and
      estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were
      compared according to age, gender, remission rate, resistance and invasion status
      of the patients. Higher than normal P450AROM expression was found in the
      pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM
      intensity had no relation to resistance or remission in patients with
      prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed
      that compared to males without invasive adenoma, males with invasive adenoma had
      higher P450AROM expression (p = 0.048). ER beta was found to have an impact on
      resistance (p = 0.049). This study shows that P450AROM expression is present in
      the pituitary tissues of patients with prolactinoma and that this presence could
      be important in development and tumor behavior of prolactinomas.

PMID- 22983692
TI  - Wellbeing for homeless people: a Salutogenic approach.
AB  - Homelessness affects considerable numbers in the UK and is caused by poverty and
      social exclusion. Much of the literature on housing and health is disease
      centric, where the experience of homelessness is described as traumatic,
      disempowering and socially isolating. Based on the Salutogenic approach, which
      calls for a positive orientation on health, the aim of this study was to explore
      the subjective lived experiences of wellbeing in the situated context of homeless
      people's lives. Nine in-depth qualitative interviews with temporarily housed
      adults (>25 years) in a socio-economically deprived region of North-west England
      were held. Accounts of renewed self-confidence, perceived resourcefulness and
      continual personal participation are said to be supporting wellbeing. A strong
      belief, or sense of coherence, in internal and external general resistance
      resources was a critical enabling factor for those living in temporary
      accommodation. Wellbeing was consistently linked with both social and formal
      activities; keeping occupied and having a strong sense of purpose were essential
      to wellbeing. In utilizing a Salutogenic approach we demonstrate how the 'context
      and meaning' of health actions can improve the understanding about the kinds of
      factors influencing wellbeing. 

PMID- 22983693
TI  - Dealing with dilemmas in health campaigning.
AB  - Campaigners on public health issues face a number of dilemmas when tactical
      choices in public debating involve uncomfortable mixtures of benefits and costs.
      Key dilemmas for campaigners are whether to acknowledge weaknesses in their own
      position, whether to advocate research to address claims by opponents, whether to
      acknowledge vested interests on their own side, whether to debate with opponents,
      whether to launch attacks on opposition individuals and groups and whether to
      criticize extreme behaviour by those on their own side. Drawing on the literature
      on scientific controversies, these dilemmas are outlined, with illustrations from
      the Australian vaccination debate. Dilemmas in health campaigning warrant
      attention because choices made can affect both the success of policy initiatives
      and the image of professions, sometimes with trade-offs between these. However,
      dilemmas have been neglected because most studies of health controversies give
      little attention to campaigning tactics. Campaigners can choose options that seem
      to maximize the likelihood of winning in the short term. However, options for
      short-term advantage may establish a precedent for approaches to campaigning that
      undermine commitment to free and open debate to possible long-term disadvantage.

PMID- 22983695
TI  - Catalyst-assisted hydride vapor phase epitaxy of GaN nanowires: exceptional
      length and constant rod-like shape capability.
AB  - The hydride vapor phase epitaxy (HVPE) process exhibits unexpected properties
      when growing GaN semiconductor nanowires (NWs). With respect to the classical
      well-known methods such as metal organic vapor phase epitaxy and molecular beam
      epitaxy, this near-equilibrium process based on hot wall reactor technology
      enables the synthesis of nanowires with a constant cylinder shape over unusual
      length. Catalyst-assisted HVPE shows a record short time process (less than 20
      min) coupled to very low precursor consumption. NWs are grown at a fast
      solidification rate (50 MUm h(-1)), facilitated by the high decomposition
      frequency of the chloride molecules involved in the HVPE process as element III
      precursors. In this work growth temperature and V/III ratio were investigated to
      determine the growth mechanism which led to such long NWs. Analysis based on the
      Ni-Ga phase diagram and the growth kinetics of near-equilibrium HVPE is proposed.

PMID- 22983697
TI  - Selective internal radiotherapy (SIRT) of hepatic tumors: how to deal with the
      cystic artery.
AB  - PURPOSE: Selective internal radiotherapy (SIRT) with the beta emitter yttrium-90
      (Y90) is a rapidly developing therapy option for unresectable liver malignancies.
      Nontarget irradiation of the gallbladder is a complication of SIRT. Thus, we
      aimed to assess different strategies to avoid infusion of Y90 into the cystic
      artery (CA). METHODS: After hepatic digital subtraction angiography and
      administration of technetium-99m-labeled human serum albumin ((99)mTc-HSA), 295
      patients with primary or secondary liver tumors underwent single-photon emission
      computed tomography/computed tomography (SPECT/CT). Different measures were taken
      before repeated Y90 mapping and SIRT to avoid unintended influx into the CA where
      necessary. Clinical symptoms, including pain, fever, or a positive Murphy sign,
      were assessed during patient follow-up. RESULTS: A significant (99)mTc-HSA
      accumulation in the gallbladder wall (higher (99)mTc-HSA uptake than in normal
      liver tissue) was seen in 20 patients. The following measures were taken to avoid
      unintended influx into the CA: temporary/permanent occlusion of the CA with
      gelfoam (n = 5)/microcoil (n = 1), induction of vasospasm with a microwire (n =
      4), or altering catheter position (n = 10). Clinical signs of cholecystitis were
      observed in only one patient after temporary CA occlusion with gelfoam and were
      successfully treated by antibiotics. Cholecystectomy was not required for any
      patient. CONCLUSION: It is important to identify possible nontarget irradiation
      of the gallbladder. The risk for radiation-induced cholecystitis can be easily
      minimized by temporary or permanent CA embolization, vasospasm induction, or
      altering the catheter position.

PMID- 22983696
TI  - De Garengeot's hernia: a comprehensive review.
AB  - PURPOSE: Acute appendicitis within a femoral hernia is a rare condition that was
      first described by Rene Jacques de Garengeot. In the present study, we summarize
      the existing evidence on de Garengeot's hernia, with special emphasis on its
      clinical presentation and diagnostic approach. METHODS: A thorough search of the
      English-language literature published between 1980 and 2011 was performed.
      Studies reporting cases of de Garengeot's hernia were selected using specific
      inclusion criteria (description of femoral hernia appendicitis, statement of
      patient demographics and symptoms, and statement of diagnostic tests performed).
      RESULTS: Thirty-one studies that encompassed 36 patients (28 women, mean age 71.5
      years) with de Garengeot's hernia were included in our analysis. Patients
      presented with a right groin mass in 35 (97 %) cases. The mass was almost always
      painful (n = 35, 97 %), while 14 (39 %) of the patients were febrile. Mean
      duration of symptoms was 5.17 days. Fifty-six percent of the groin masses were
      erythematous. Leukocytosis was present in 67 % of the patients, and 25 patients
      underwent imaging investigation with X-ray (n = 11), Ultrasound (n = 5) or
      Computed Tomography (CT, n = 9). Twenty percent of the Ultrasound and 44 % of the
      CT studies were diagnostic, leading to an overall rate of 14 % of femoral hernia
      appendicitis preoperative diagnosis. Eighty-one percent of the patients underwent
      herniorrhaphy with sutures while a mesh was used in 19 %. Mean hospital stay was
      6.23 days. CONCLUSION: Preoperative diagnosis of de Garengeot's hernia is
      difficult due to its atypical clinical presentation. Further surgical treatment
      depends on the surgeon's sound clinical judgment.

PMID- 22983698
TI  - Everolimus-induced pneumonitis after drug-eluting stent implantation: a case
      report.
AB  - Despite the wide use of everolimus as an antineoplastic coating agent for
      coronary stents to reduce the rate of restenosis, little is known about the
      health hazards of everolimus-eluting stents (EES). We describe a case of
      pneumonitis that developed 2 months after EES implantation for angina. Lung
      pathology demonstrated an organizing pneumonia pattern that responded to
      corticosteroid therapy. Although the efficacy of EES for ischemic heart disease
      is well established, EES carries a risk of pneumonitis. 

PMID- 22983699
TI  - Alpha-momorcharin, a RIP produced by bitter melon, enhances defense response in
      tobacco plants against diverse plant viruses and shows antifungal activity in
      vitro.
AB  - Alpha-momorcharin (alpha-MMC) is type-1 ribosome inactivating proteins (RIPs)
      with molecular weight of 29 kDa and has lots of biological activity. Our recent
      study indicated that the alpha-MMC purified from seeds of Momordica charantia
      exhibited distinct antiviral and antifungal activity. Tobacco plants pre-treated
      with 0.5 mg/mL alpha-MMC 3 days before inoculation with various viruses showed
      less-severe symptom and less reactive oxygen species (ROS) accumulation compared
      to that inoculated with viruses only. Quantitative real-time PCR analysis
      revealed that the replication levels of viruses were lower in the plants treated
      with the alpha-MMC than control plants at 15 days post inoculation. Moreover, the
      coat protein expression of viruses was almost completely inhibited in plants
      which were treated with the alpha-MMC compared with control plants. Furthermore,
      the SA-responsive defense-related genes including non-expressor of pathogenesis
      related genes 1 (NPR1), PR1, PR2 were up-regulated and activities of some
      antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT),
      peroxidase (POD) were increased after the alpha-MMC treatment. In addition, the
      alpha-MMC (500 MUg/mL) revealed remarkable antifungal effect against
      phytopathogenic fungi, in the growth inhibition range 50.35-67.21 %, along with
      their MIC values ranging from 100 to 500 MUg/mL. The alpha-MMC had also a strong
      detrimental effect on spore germination of all the tested plant pathogens along
      with concentration as well as time-dependent kinetic inhibition of Sclerotinia
      sclerotiorum. The alpha-MMC showed a remarkable antiviral and antifungal effect
      and hence could possibly be exploited in crop protection for controlling certain
      important plant diseases.

PMID- 22983701
TI  - Primary yolk sac tumor in diaphragm.

PMID- 22983700
TI  - Dynamic expression of small RNA populations in larch (Larix leptolepis).
AB  - Small RNAs (sRNAs) are emerging as essential regulators of biological processes.
      However, several studies have reported that gymnosperms do not express
      appreciable amounts of 24-nt sRNAs, and conifers in particular may have a unique
      sRNA-silencing signature. Here, we compared the sRNA transcriptomes of Japanese
      larch somatic embryos (SE) and seedlings. SE sRNAs exhibited a length bias toward
      24 nt, while seedlings showed a bias toward a 21-nt length. We also confirmed
      that larch is capable of producing 24-nt sRNAs based on a polyacrylamide gel
      analysis. The sRNA expression patterns varied according to developmental stage,
      which might be associated with Dicer-like 3 and RNA-dependent RNA polymerase2
      (RDR2) levels. Our data suggest that many MIR loci that produce canonical
      microRNAs (miRNAs, 20-22 nt) and long sRNAs (23-26 nt) have dual functions; the
      latter were preferentially produced in SE compared to seedlings. However, the
      ratio of miRNAs to total sRNAs in seedlings was higher than in SE, and most
      miRNAs were upregulated in seedlings. Trans-acting small interfering RNAs (ta
      siRNAs) generated from TAS3 triggered by miR390 were identified, and levels of
      the three detected ta-siRNAs peaked in mature embryos, which was not consistent
      with the lowest RDR6 level. These findings indicate that larch, and possibly
      other gymnosperms, shares a common sRNA pathway with other land plants, and that
      the sRNA distribution pattern varies according to developmental stage, which may
      be attributable to the expression of sRNA pathway genes.

PMID- 22983702
TI  - Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by
      caveolae via VEGF/KDR pathway.
AB  - Endothelial hyperpermeability induced by hyperglycemia is the initial step in the
      development of atherosclerosis, one of the most serious cardiovascular
      complications in diabetes. In the present study, we investigated the effects of
      resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma
      polygonum cuspidatum, on permeability in vitro and the molecular mechanisms
      involved. Permeability was assessed by the efflux of fluorescein isothiocyanate
      (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA
      levels, protein expressions, and secretions were measured by quantitative real
      time PCR, western blot, and ELISA, respectively. Increased permeability and
      caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high
      glucose. Resveratrol treatment alleviated the hyperpermeability and the
      overexpression of cav-1 induced by high glucose in a dose-dependent manner. beta
      Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability
      caused by high glucose. Resveratrol also down-regulated the increased expressions
      of vascular endothelial growth factor (VEGF) and kinase insert domain receptor
      (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway
      by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability
      and the cav-1 overexpression induced by high glucose. The above results
      demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by
      high glucose via VEGF/KDR pathway.

PMID- 22983703
TI  - Atrial fibrillation pacing decreases intravascular shear stress in a New Zealand
      white rabbit model: implications in endothelial function.
AB  - Atrial fibrillation (AF) is characterized by multiple rapid and irregular atrial
      depolarization, leading to rapid ventricular responses exceeding 100 beats per
      minute (bpm). We hypothesized that rapid and irregular pacing reduced
      intravascular shear stress (ISS) with implication to modulating endothelial
      responses. To simulate AF, we paced the left atrial appendage of New Zealand
      White rabbits (n = 4) at rapid and irregular intervals. Surface electrical
      cardiograms were recorded for atrial and ventricular rhythm, and intravascular
      convective heat transfer was measured by microthermal sensors, from which ISS was
      inferred. Rapid and irregular pacing decreased arterial systolic and diastolic
      pressures (baseline, 99/75 mmHg; rapid regular pacing, 92/73; rapid irregular
      pacing, 90/68; p < 0.001, n = 4), temporal gradients ([Formula: see text] from
      1,275 +/- 80 to 1,056 +/- 180 dyne/cm(2) s), and reduced ISS (from baseline at
      32.0 +/- 2.4 to 22.7 +/- 3.5 dyne/cm(2)). Computational fluid dynamics code
      demonstrated that experimentally inferred ISS provided a close approximation to
      the computed wall shear stress at a given catheter to vessel diameter ratio,
      shear stress range, and catheter position. In an in vitro flow system in which
      time-averaged shear stress was maintained at [Formula: see text] , we further
      demonstrated that rapid pulse rates at 150 bpm down-regulated endothelial nitric
      oxide, promoted superoxide (O 2 (.-) ) production, and increased monocyte binding
      to endothelial cells. These findings suggest that rapid pacing reduces ISS and
      [Formula: see text] , and rapid pulse rates modulate endothelial responses. 

PMID- 22983704
TI  - Approaches to homozygosity mapping and exome sequencing for the identification of
      novel types of CDG.
AB  - In the past decade, the identification of most genes involved in Congenital
      Disorders of Glycosylation (CDG) (type I) was achieved by a combination of
      biochemical, cell biological and glycobiological investigations. This has been
      truly successful for CDG-I, because the candidate genes could be selected on the
      basis of the homology of the synthetic pathway of the dolichol linked
      oligosaccharide in human and yeast. On the contrary, only a few CDG-II defects
      were elucidated, be it that some of the discoveries represent wonderful
      breakthroughs, like e.g, the identification of the COG defects. In general, many
      rare genetic defects have been identified by positional cloning. However, only a
      few types of CDG have effectively been elucidated by linkage analysis and so
      called reverse genetics. The reason is that the families were relatively small
      and could-except for CDG-PMM2-not be pooled for analysis. Hence, a large number
      of CDG cases has long remained unsolved because the search for the culprit gene
      was very laborious, due to the heterogeneous phenotype and the myriad of
      candidate defects. This has changed when homozygosity mapping came of age,
      because it could be applied to small (consanguineous) families. Many novel CDG
      genes have been discovered in this way. But the best has yet to come: what we are
      currently witnessing, is an explosion of novel CDG defects, thanks to exome
      sequencing: seven novel types were published over a period of only two years. It
      is expected that exome sequencing will soon become a diagnostic tool, that will
      continuously uncover new facets of this fascinating group of diseases.

PMID- 22983705
TI  - Neutralization of B. anthracis toxins during ex vivo phagocytosis.
AB  - Glycoconjugates (GCs) are recognized as stimulation and signaling agents,
      affecting cell adhesion, activation, and growth of living organisms. Among GC
      targets, macrophages are considered ideal since they play a central role in
      inflammation and immune responses against foreign agents. In this context, we
      studied the effects of highly selective GCs in neutralizing toxin factors
      produced by B. anthracis during phagocytosis using murine macrophages. The
      effects of GCs were studied under three conditions: A) prior to, B) during, and
      C) following exposure of macrophages to B. anthracis individual toxin (protective
      antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF,
      PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis
      analysis including direct microscopic observation of macrophage viability, and
      macrophage activation. Our results demonstrated that macrophages are more prone
      to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion
      results in a higher phagocytosis rate and toxin complex neutralization during
      phagocytosis. In addition, GCs enhance macrophage viability, activate
      macrophages, and stimulate nitric oxide (NO) production. The present study may be
      helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating
      properties. In addition, our study could suggest GCs as new targets for existing
      vaccines and the prospective development of vaccines and immunomodulators used to
      combat the effects of B. anthracis.

PMID- 22983706
TI  - Photosensitizing properties of compounds related to benzophenone.
AB  - Benzophenone is a phototoxic compound with absorption maxima in the ultraviolet A
      (UVA) and ultraviolet B (UVB) range. Many benzophenone derivatives are known to
      be photosensitizing. On the other hand, 2-hydroxy-4-methoxybenzophenone is used
      as a photoprotective agent. The aim of the present study was to analyse a range
      of benzophenone derivatives and thus examine the effects of molecular changes in
      the benzophenone molecule on phototoxic behaviour. Phototoxicity was tested by an
      in vitro photohaemolysis test. The tested compounds were benzophenone itself and
      the derivatives 2-hydroxybenzophenone, 2-aminobenzophenone, 2-benzoylbenzoic
      acid, 3-hydroxybenzophenone, and 4-hydroxybenzo-phenone, as well as the
      structurally similar compounds 9-fluorenone, 9-fluorenone-2-carboxylic acid,
      cyclohexyl phenyl ketone, and 1,4-naphtho-quinone. It was shown that minor
      changes in molecular structure can result in highly different phototoxic
      characteristics.

PMID- 22983707
TI  - A genomic regulatory element that directs assembly and function of immune
      specific AP-1-IRF complexes.
AB  - Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and
      dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF
      composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells
      is enigmatic given the absence of specific Ets partners. Chromatin
      immunoprecipitation sequencing in T helper 17 (T(H)17) cells reveals that IRF4
      targets sequences enriched for activating protein 1 (AP-1)-IRF composite elements
      (AICEs) that are co-bound by BATF, an AP-1 factor required for T(H)17, B, and
      dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally
      divergent AICEs to promote gene activation and T(H)17 differentiation. The AICE
      motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in
      T(H)2, B, and dendritic cells. This genomic regulatory element and cognate
      factors appear to have evolved to integrate diverse immunomodulatory signals.

PMID- 22983708
TI  - Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of
      autism.
AB  - The genetic heterogeneity of autism poses a major challenge for identifying
      mechanism-based treatments. A number of rare mutations are associated with
      autism, and it is unclear whether these result in common neuronal alterations.
      Monogenic syndromes, such as fragile X, include autism as one of their
      multifaceted symptoms and have revealed specific defects in synaptic plasticity.
      We discovered an unexpected convergence of synaptic pathophysiology in a
      nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3
      knockout mice (a model for nonsyndromic autism) exhibited disrupted
      heterosynaptic competition and perturbed metabotropic glutamate receptor
      dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be
      rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the
      possibility of reverting neuronal circuit alterations in autism after the
      completion of development.

PMID- 22983709
TI  - Dynamics of DNA supercoils.
AB  - DNA in cells exhibits a supercoiled state in which the double helix is
      additionally twisted to form extended intertwined loops called plectonemes.
      Although supercoiling is vital to many cellular processes, its dynamics remain
      elusive. In this work, we directly visualize the dynamics of individual
      plectonemes. We observe that multiple plectonemes can be present and that their
      number depends on applied stretching force and ionic strength. Plectonemes moved
      along DNA by diffusion or, unexpectedly, by a fast hopping process that
      facilitated very rapid (<20 milliseconds) long-range plectoneme displacement by
      nucleating a new plectoneme at a distant position. These observations directly
      reveal the dynamics of plectonemes and identify a mode of movement that allows
      long-distance reorganization of the conformation of the genome on a millisecond
      time scale.

PMID- 22983711
TI  - Metagenome mining reveals polytheonamides as posttranslationally modified
      ribosomal peptides.
AB  - It is held as a paradigm that ribosomally synthesized peptides and proteins
      contain only l-amino acids. We demonstrate a ribosomal origin of the marine
      sponge-derived polytheonamides, exceptionally potent, giant natural-product
      toxins. Isolation of the biosynthetic genes from the sponge metagenome revealed a
      bacterial gene architecture. Only six candidate enzymes were identified for 48
      posttranslational modifications, including 18 epimerizations and 17 methylations
      of nonactivated carbon centers. Three enzymes were functionally validated, which
      showed that a radical S-adenosylmethionine enzyme is responsible for the
      unidirectional epimerization of multiple and different amino acids. Collectively,
      these complex alterations create toxins that function as unimolecular
      minimalistic ion channels with near-femtomolar activity. This study broadens the
      biosynthetic scope of ribosomal systems and creates new opportunities for peptide
      and protein bioengineering.

PMID- 22983710
TI  - Cilia at the node of mouse embryos sense fluid flow for left-right determination
      via Pkd2.
AB  - Unidirectional fluid flow plays an essential role in the breaking of left-right
      (L-R) symmetry in mouse embryos, but it has remained unclear how the flow is
      sensed by the embryo. We report that the Ca(2+) channel Polycystin-2 (Pkd2) is
      required specifically in the perinodal crown cells for sensing the nodal flow.
      Examination of mutant forms of Pkd2 shows that the ciliary localization of Pkd2
      is essential for correct L-R patterning. Whereas Kif3a mutant embryos, which lack
      all cilia, failed to respond to an artificial flow, restoration of primary cilia
      in crown cells rescued the response to the flow. Our results thus suggest that
      nodal flow is sensed in a manner dependent on Pkd2 by the cilia of crown cells
      located at the edge of the node.

PMID- 22983712
TI  - An exploratory study of social connections and drug usage among Filipino
      Americans.
AB  - This research reports information from semi-structured interviews with 14
      northern California Filipino Americans to explore how social connections are
      associated with methamphetamine use. The interviews examine how the social
      connections of Filipino American methamphetamine users are influenced by class
      and generational status. I hypothesize that drug users become involved in social
      networks that facilitate drug use and that cases of recovery occur among users
      when they change their social networks. Generational differences in age of first
      methamphetamine use suggest that drug usage among first generation users may be a
      way of coping with social class disadvantages. User social networks within social
      class groups generate ethnic solidarity and highlight the existence of a shared
      culture that plays an adaptive role in aiding survival, but such support does not
      appear to help Filipinos stop methamphetamine use. The realization by users that
      their networks have enabled and reinforced their drug usage serves as a major
      turning point in helping them "break free" from the social ties that foster
      continued usage. Those that maintain their ties to user networks tend to remain
      users. 

PMID- 22983714
TI  - A low-temperature-active alkaline pectate lyase from Xanthomonas campestris ACCC
      10048 with high activity over a wide pH range.
AB  - Alkaline pectate lyases are favorable for the textile industry. Here, we report
      the gene cloning and expression of a low-temperature-active alkaline pectate
      lyase (PL D) from Xanthomonas campestris ACCC 10048. Deduced PL D consists of a
      putative 27-residue signal peptide and a catalytic domain of 320 residues
      belonging to family PF09492. Recombinant PL D (r-PL D) produced in Escherichia
      coli was purified to electrophoretic homogeneity with a single step of Ni(2+)-NTA
      affinity chromatography and showed an apparent molecular weight of ~38 kDa. The
      pH and temperature optima of r-PL D were found to be 9.0  degrees C and 30 
      degrees C, respectively. Compared with its microbial counterparts, r-PL D had
      higher activity over a wide pH range (>45 % of the maximum activity at pH 3.0
      12.0) and at lower temperatures (>35 % of activity even at 0  degrees C). The
      K(m) and V(max) values of r-PL D for polygalacturonic acid were 4.9 gl(-1) and
      30.1 MUmolmin(-1) mg(-1), respectively. Compared with the commercial compound
      pectinase from Novozymes, r-PL D showed similar efficacy in reducing the
      intrinsic viscosity of polygalacturonic acid (35.1 % vs. 36.5 %) and in
      bioscouring of jute (10.25 % vs. 10.82 %). Thus, r-PL D is a valuable additive
      candidate for the textile industry.

PMID- 22983713
TI  - From models to ornamentals: how is flower senescence regulated?
AB  - Floral senescence involves an ordered set of events coordinated at the plant,
      flower, organ and cellular level. This review assesses our current understanding
      of the input signals, signal transduction and cellular processes that regulate
      petal senescence and cell death. In many species a visible sign of petal
      senescence is wilting. This is accompanied by remobilization of nutrients from
      the flower to the developing ovary or to other parts of the plant. In other
      species, petals abscise while still turgid. Coordinating signals for floral
      senescence also vary across species. In some species ethylene acts as a central
      regulator, in others floral senescence is ethylene insensitive and other growth
      regulators are implicated. Due to the variability in this coordination and
      sequence of events across species, identifying suitable models to study petal
      senescence has been challenging, and the best candidates are reviewed.
      Transcriptomic studies provide an overview of the MAP kinases and transcription
      factors that are activated during petal senescence in several species including
      Arabidopsis. Our understanding of downstream regulators such as autophagy genes
      and proteases is also improving. This gives us insights into possible signalling
      cascades that regulate initiation of senescence and coordination of cell death
      processes. It also identifies the gaps in our knowledge such as the role of
      microRNAs. Finally future prospects for using all this information from model to
      non-model species to extend vase life in ornamental species is reviewed. 

PMID- 22983715
TI  - Detoxification and fermentation of pyrolytic sugar for ethanol production.
AB  - The sugars present in bio-oil produced by fast pyrolysis can potentially be
      fermented by microbial organisms to produce cellulosic ethanol. This study shows
      the potential for microbial digestion of the aqueous fraction of bio-oil in an
      enrichment medium to consume glucose and produce ethanol. In addition to glucose,
      inhibitors such as furans and phenols are present in the bio-oil. A pure glucose
      enrichment medium of 20 g/l was used as a standard to compare with glucose and
      aqueous fraction mixtures for digestion. Thirty percent by volume of aqueous
      fraction in media was the maximum additive amount that could be consumed and
      converted to ethanol. Inhibitors were removed by extraction, activated carbon,
      air stripping, and microbial methods. After economic analysis, the cost of
      ethanol using an inexpensive fermentation medium in a large scale plant is
      approximately $14 per gallon.

PMID- 22983716
TI  - Scale-up of human embryonic stem cell culture using a hollow fibre bioreactor.
AB  - The commercialisation of human embryonic stem cell derived cell therapies for
      large patient populations is reliant on both minimising expensive and variable
      manual-handling methods whilst realising economies of scale. The Quantum Cell
      Expansion System, a hollow fibre bioreactor (Terumo BCT), was used in a pilot
      study to expand 60 million human embryonic stem cells to 708 million cells.
      Further improvements can be expected with optimisation of media flow rates
      throughout the run to better control the cellular microenvironment. High levels
      of pluripotency marker expression were maintained on the bioreactor, with 97.7 %
      of cells expressing SSEA-4 when harvested.

PMID- 22983717
TI  - Activity-guided screening of bioactive natural compounds implementing a new
      glucocorticoid-receptor-translocation assay and detection of new anti
      inflammatory steroids from bacteria.
AB  - Using an in vitro cell-based assay in a flow-design, we have applied activity
      guided screening to search for new bioactive compounds isolated from
      microorganisms. A first assay employs the stable expression of nuclear factor
      kappa B (NF-kappaB) while a second assay utilizes the glucocorticoid receptor
      (GR) coupled to green fluorescent protein. A specialized assay was implemented
      for both the translocation of NF-kappaB and to inhibit the translocation of
      cytokine-mediated NF-kappaB. In addition, we developed in a wide palette of cell
      lines used for a highly specialized GR-translocation assay to detect anti
      inflammatory effects. This approach demonstrates the straight-forward combination
      of cell-based assays arranged with an automated fluorescence microscope. This
      allows for the direct sorting of extracts which are acting in a pharmaceutically
      interesting way. Initial results using this technique have led to the detection
      of new anti-inflammatory steroids from bacterial crude extracts.

PMID- 22983718
TI  - Chlorophyllin abrogates canonical Wnt/beta-catenin signaling and angiogenesis to
      inhibit the development of DMBA-induced hamster cheek pouch carcinomas.
AB  - BACKGROUND: Chlorophyllin, a water soluble semi-synthetic food-grade derivative
      is reported to exhibit a wide range of beneficial health effects. We investigated
      the effect of chlorophyllin supplementation on Wnt/beta-catenin and vascular
      endothelial growth factor (VEGF) signaling in the 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model. METHODS AND
      RESULTS: Hamsters were divided into 4 groups. The right buccal pouches of group 1
      and 2 hamsters were painted with 0.5 % DMBA for 14 weeks. Group 2 animals
      received in addition chlorophyllin (4 mg/kg bw) in the diet. Group 3 animals
      received chlorophyllin alone and group 4 animals served as control. mRNA and
      protein expression of components of Wnt, VEGF, and PI3K/Akt signaling pathways
      were analyzed by RT-PCR and Western blot analysis. Dietary chlorophyllin
      administration suppressed the development of HBP carcinomas by altering the
      expression of several components of the Wnt/beta-catenin signaling pathway. This
      was associated with inhibition of angiogenesis as evidenced by decreased
      expression of the proangiogenic factors HIF-1alpha, VEGF, and VEGFR2.
      Chlorophyllin administration also downregulated the expression of histone
      deacetylases involved in epigenetic regulation of tumor angiogenesis. CONCLUSION:
      Dietary chlorophyllin that abrogates Wnt/beta-catenin and VEGF signaling by
      targeting a multitude of key signaling molecules is an attractive candidate for
      preventing tumor progression.

PMID- 22983719
TI  - Developing a model to estimate the potential impact of municipal investment on
      city health.
AB  - This article summarizes a process which exemplifies the potential impact of
      municipal investment on the burden of cardiovascular disease (CVD) in city
      populations. We report on Developing an evidence-based approach to city public
      health planning and investment in Europe (DECiPHEr), a project part funded by the
      European Union. It had twin objectives: first, to develop and validate a
      vocational educational training package for policy makers and political decision
      takers; second, to use this opportunity to iterate a robust and user-friendly
      investment tool for maximizing the public health impact of 'mainstream' municipal
      policies, programs and investments. There were seven stages in the development
      process shared by an academic team from Sheffield Hallam University and partners
      from four cities drawn from the WHO European Healthy Cities Network. There were
      five iterations of the model resulting from this process. The initial focus was
      CVD as the biggest cause of death and disability in Europe. Our original
      prototype 'cost offset' model was confined to proximal determinants of CVD,
      utilizing modified 'Framingham' equations to estimate the impact of population
      level cardiovascular risk factor reduction on future demand for acute hospital
      admissions. The DECiPHEr iterations first extended the scope of the model to
      distal determinants and then focused progressively on practical interventions.
      Six key domains of local influence on population health were introduced into the
      model by the development process: education, housing, environment, public health,
      economy and security. Deploying a realist synthesis methodology, the model then
      connected distal with proximal determinants of CVD. Existing scientific evidence
      and cities' experiential knowledge were 'plugged-in' or 'triangulated' to
      elaborate the causal pathways from domain interventions to public health impacts.
      A key product is an enhanced version of the cost offset model, named Sheffield
      Health Effectiveness Framework Tool, incorporating both proximal and distal
      determinants in estimating the cost benefits of domain interventions. A key
      message is that the insights of the policy community are essential in developing
      and then utilising such a predictive tool. 

PMID- 22983720
TI  - Are your asset data as good as you think? Conducting a comprehensive census of
      built assets to improve urban population health.
AB  - Secondary data sources are widely used to measure the built asset environment,
      although their validity for this purpose is not well-established. Using community
      engaged research methodology, this study conducted a census of public-facing,
      built assets via direct observation and then tested the performance of these data
      against widely used secondary datasets. After engaging community organizations, a
      community education campaign was implemented. Using web-enabled cell phones and a
      web-based application prepopulated with the secondary data, census workers
      verified, modified, and/or added assets using street-level observation,
      supplementing data with web searches and telephone calls. Data were uploaded to
      http://www.SouthSideHealth.org . Using direct observation as the criterion
      standard, the sensitivity of secondary datasets was calculated. Of 5,773 assets
      on the prepopulated list, direct observation of public-facing assets verified
      1,612 as operating; another 653 operating assets were newly identified.
      Sensitivity of the commercial list for nonresidential, operating assets was 61 %.
      Using the asset census as the criterion standard, secondary datasets were
      incomplete and inaccurate. Comprehensive, accurate built asset data are needed to
      advance urban health research, inform policy, and improve individuals' access to
      assets. 

PMID- 22983721
TI  - Epidemiology, sexual risk behavior, and HIV prevention practices of men who have
      sex with men using GRINDR in Los Angeles, California.
AB  - Young men who have sex with men (YMSM) are at alarming risk for HIV acquisition,
      demonstrating the highest rates of incident infection of any age-risk group.
      GRINDR is a global positioning service-based social networking application
      popular with YMSM for sexual partnering. To assess the characteristics of YMSM
      who use GRINDR, we conducted a computer-assisted self-interview-based survey of
      375 YMSM using GRINDR in metropolitan Los Angeles, recruited using the GRINDR
      platform. The median age was 25 (interquartile range, 22-27) years old, 42.4 %
      caucasian, 6.4 % African American, 33.6 % Latino, and 14.1 % Asian/Pacific
      Islander. Participants reported high rates of sexual partnering and unprotected
      anal intercourse (UAI). The majority (70 %) of those reporting unprotected anal
      intercourse reported low perception of HIV-acquisition risk. Of the participants,
      83.1 % reported HIV testing within the past 12 months; 4.3 % had never been HIV
      tested. Of the participants, 4.5 % reported HIV-positive serostatus; 51.7 %
      indicated that they would be interested in participating in a future HIV
      prevention trial. Latinos were more likely than either caucasians or African
      Americans to endorse trial participation interest (odds ratio, 1.9; 95 %
      confidence interval [1.1-3.3]). HIV-positive test results were associated with
      increased number of anal sex partners in the past 3 months (adjusted odds ratio
      (AOR), 1.53 [0.97-2.40]), inconsistent inquiry about partners' serostatus (AOR,
      3.63 [1.37-9.64]), reporting the purpose for GRINDR use including "friendship"
      (AOR, 0.17 [0.03-1.06), and meeting a sexual partner in a bookstore in the past 3
      months (AOR, 33.84 [0.99-1152]). Men recruited via GRINDR were high risk for HIV
      acquisition or transmission and interested in clinical trial participation,
      suggesting potential for this method to be used for recruitment of YMSM to HIV
      prevention trials. 

PMID- 22983722
TI  - Impact of HIV-1 replication on immunological evolution during long-term dual
      boosted protease inhibitor therapy.
AB  - To explore CD4-cell and viral evolution in relation to different levels of HIV-1
      replication, as observed during protease inhibitor (PI)-based antiretroviral
      therapy. Adult HIV-1 infected cohort patients, receiving historical salvage
      therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either
      lopinavir (800 mg) or atazanavir (300 mg) for >36 weeks were retrospectively
      analysed for highest detectable viral load up to week 96 and assigned to groups
      according to the viral load level: always <50 copies/ml (1), 50-199 copies/ml
      (2), 200-499 copies/ml (3) and >=500 copies/ml (4). A total of 126 patients were
      evaluated; at baseline, median CD4-cell count was 204/mm(3), HIV-1 RNA was 5.13
      Log10-copies/ml and duration of prior HIV-1 infection was 11.7 years. Patients
      were assigned by 43, 30, 7 and 20 % to groups 1-4. Median observation time was
      136 weeks (range: 38-304); at weeks 48/96, the CD4-cell gains for groups 1-4 were
      +88/+209, +209/+349, +67/+300 and +114.5/+ 128, respectively. After fitting data
      in a linear fixed effect model, ascending CD4 slopes were continuously increasing
      for group 1, similarly for 2 and clearly decreasing for 3-4 (p = 0.0006). Of 25
      individuals from group 4, patient number with major IAS-USA protease mutations
      increased from 5 to 10 before and after failing PI therapy, whereas minor
      mutations remained stable (n = 18). On double-boosted PI therapy, CD4-cell
      increases through week 96 were similar for patients at always undetectable or
      with detection of low viral load. Viral detection >200 copies/ml was associated
      with decreasing CD4-cell slopes and emergence of major mutations, supporting this
      as benchmark for virological failure definition on PI therapy.

PMID- 22983723
TI  - Dissipation of pendimethalin in soil and its residues in chickpea (Cicer
      arietinum L.) under field conditions.
AB  - Disappearance of pendimethalin in the soil of chickpea (Cicer arietinum L.) at 0
      110 days, and terminal residues in plant samples have been studied under field
      conditions. Pendimethalin was applied as pre-emergence herbicide at 750, 350 and
      180 g a.i. ha(-1) in winter, in chickpea crop. The dissipation of pendimethalin
      in the chickpea field soil conditions followed first order kinetics showing a
      half-life of 11.23 days averaged over all doses. Low pendimethalin residues were
      found in plant samples. 0.025, 0.015, <0.001 MUg g(-1) residues of pendimethalin
      were found in grains at 750, 350 and 185 g a.i. ha(-1) treatments, respectively.
      Much lower pendimethalin residues were found in straw viz. 0.015 to <0.001 MUg g(
      1) at 750, 350 and 185 g a.i. ha(-1) treatments, respectively.

PMID- 22983724
TI  - Determination of residual flubendiamide in the cabbage by QuEChERS-liquid
      chromatography-tandem mass spectrometry.
AB  - Flubendiamide, which belongs to the new chemical class of phthalic acid diamides,
      is widely used against lepidopteron pests in a variety of vegetable and rice
      pests. It provides superior plant protection against a broad range of
      economically important lepidopterous pests, including Spodoptera exigua and
      Plutella xylostella. A determination method of flubendiamide in the cabbage was
      established in this paper. Flubendiamide in the cabbage was extracted with
      acetonitrile and ultrasonic extraction, and was purified by QuEChERS and analyzed
      by LC-MS/MS (liquid chromatography-tandem mass spectrometry). The results
      indicated that the average recovery of flubendiamide in the cabbage was 81.27%
      91.45%, the coefficient of variation was 1.79%-4.81%, and the lowest detection
      concentration was 0.3 MUg/kg. The extraction of flubendiamide from the cabbage
      and its analysis was in accordance with the pesticide residue criterion, i.e.,
      simple, rapid, accurate, reproducible, stable, separatory, and convenient. It
      identifies and quantifies trace-level flubendiamide residues in the cabbage
      extracts using LC-MS/MS in the ESI negative mode coupled with the QuEChERS
      method.

PMID- 22983725
TI  - Dissipation and residues of flutriafol in wheat and soil under field conditions.
AB  - The dissipation and residues of flutriafol in wheat and soil under field
      conditions in Beijing, Anhui and Shandong in China were determined based on high
      performance liquid chromatography. Flutriafol were extracted with acetonitrile
      and cleaned up by solid-phase extraction with florisil cartridges before UV
      detection. The limits of detection and quantification of flutriafol were 0.04 ng
      and 0.01 mg/kg for both wheat and soil samples, respectively. The mean recoveries
      ranged from 93.4% to 96.4%, with relative standard deviation between 3.8% and
      6.8% at three spiked levels (0.01, 0.1, 1.0 mg/kg). Half-lives were 13.3, 9.9 and
      13.6 days in soil, while 15.2, 10.8 and 9.2 days in wheat plant in Beijing, Anhui
      and Shandong, respectively. The terminal residues of flutriafol were below the
      maximum residue limit 0.02 mg/kg set by Japan in wheat when pre-harvest interval
      were 35 days.

PMID- 22983727
TI  - QSAR of acute toxicity of halogenated phenol to green fluorescent protein by
      using density functional theory.
AB  - A novel approach was established to predict toxicity of environmental pollutants
      by using green fluorescent protein (GFP) as bio-marker. In the approach,
      recombinant Escherichia coli was constructed to express GFP. The toxicity values
      (-lgEC (50)) of 14 halogenated phenols to recombinant E. coli with GFP gene were
      measured. And optimized calculation was carried out at B3LYP/6-31G* level using
      density functional theory method. Based on the MTLSER model, the obtained
      parameters were taken as theoretical descriptors to establish the novel QSAR
      model for predicting -lgEC (50) (R (2) = 0.922). The model includes two variables
      (standard entropy (S (theta)) and the most negative atomic net charges of the
      molecule (q (-))). The results of cross-validation test (q (2) = 0.868) indicate
      the model of this study has optimum stability, which shows that it is feasible to
      predict to toxicity of chemistry utilizing recombinant E. coli with GFP gene.

PMID- 22983726
TI  - Metal contamination and the epidemic of congenital birth defects in Iraqi cities.
AB  - Between October 1994 and October 1995, the number of birth defects per 1,000 live
      births in Al Basrah Maternity Hospital was 1.37. In 2003, the number of birth
      defects in Al Basrah Maternity Hospital was 23 per 1,000 live births. Within less
      than a decade, the occurrence of congenital birth defects increased by an
      astonishing 17-fold in the same hospital. A yearly account of the occurrence and
      types of birth defects, between 2003 and 2011, in Al Basrah Maternity Hospital,
      was reported. Metal levels in hair, toenail, and tooth samples of residents of Al
      Basrah were also provided. The enamel portion of the deciduous tooth from a child
      with birth defects from Al Basrah (4.19 MUg/g) had nearly three times higher lead
      than the whole teeth of children living in unimpacted areas. Lead was 1.4 times
      higher in the tooth enamel of parents of children with birth defects (2,497 +/-
      1,400 MUg/g, mean +/- SD) compared to parents of normal children (1,826 +/- 1,819
      MUg/g). Our data suggested that birth defects in the Iraqi cities of Al Basrah
      (in the south of Iraq) and Fallujah (in central Iraq) are mainly folate
      dependent. This knowledge offers possible treatment options and remediation plans
      for at-risk Iraqi populations.

PMID- 22983728
TI  - Assessing estrogenic chemicals in anchovy and mussel samples from Karachi,
      Pakistan with the yeast estrogen screen bioassay.
AB  - Endocrine disrupting chemicals (EDCs) are introduced into the aquatic environment
      through industrial and municipal effluents along with urban and agricultural
      runoffs. Exposure of aquatic organisms to EDCs may lead to hormonal disruption
      and adverse health effects. The goals of our study were: to collect anchovy and
      mussel samples from the coastal region of Karachi, to use the yeast estrogen
      screen (YES) bioassay in estimating xeno-estrogen content in these samples, and
      to investigate if the bioassay could be used to quantify known amounts of 17beta
      estradiol (E2) injected into cod and salmon fillets. Results of the studies
      showed that mussel estrogenic activity in Karachi decreased in the order of
      Buleji point 1 (8.91 +/- 4.77, mean +/- SD) > Paradise point 1 (1.72 +/- 0.81) >
      Paradise point 2 (0.61 +/- 0.84) ng E2 equivalents/g wet wt (p < 0.05). By
      comparison, anchovy estrogenic activity at Korangi/Phitti Creek was much higher
      than at Manora. Together, these results confirmed previous reports that both
      Buleji point 1 and Korangi/Phitti Creek were the most contaminated areas of
      Karachi. The YES bioassay was only a semi-quantitative method in determining the
      contents of xeno-estrogens in aquatic organisms; it consistently overestimated
      the amounts of E2 injected into cod and salmon fillets due to additive and/or non
      additive interactions between E2 and endogenous estrogens. Nevertheless, the YES
      bioassay was able to identify the contaminated sites in the coastal region of
      Karachi.

PMID- 22983729
TI  - Anatomical and CT angiographic study of superior gluteal neurovascular pedicle:
      implications for hip surgery.
AB  - PURPOSE: To identify the site of incision with the lowest risk of injury of the
      superior gluteal neurovascular pedicle in the total hip arthroplasty with
      Hardinge's direct lateral approach. METHODS: Eight fresh donated bodies were
      dissected and the branches of the superior gluteal nerve (SGN) and superior
      gluteal artery (SGA) were dissected. The distance between the SGA and the apex of
      greater trochanter (GT) was also evaluated in vivo in 29 patients by CT
      angiography. RESULTS: We observed 12 spray pattern and 4 transverse neural trunk
      pattern of the SGN. In all cases the nerve runs inferiorly to the artery, with a
      mean distance of 0.5 cm. At the CT angiography the average distance between the
      main branch of SGA and the GT was 5.2 cm, indicating a mean distance of 4.7 cm
      from the SGN to the GT. Terminal branches of SGA are found until 2.7 cm from GT.
      CONCLUSIONS: This study analyzed the relationships between superior gluteal
      neurovascular pedicle and the GT in vivo (considering also the muscular tone),
      showing that during direct lateral access a safe area of 4.7 cm exists from the
      GT to the SGN and of 3.5 cm to its lower rami.

PMID- 22983730
TI  - The lumbar sympathetic trunk: its visibility and distance to two anatomical
      landmarks.
AB  - OBJECTIVE: The lumbar sympathetic trunk's (LST) distance to two anatomical
      landmarks, the costal process and medial margin of the psoas muscle, was assessed
      due to its use as landmarks for lumbar sympathetic blocks: the costal process for
      fluoroscopic guided techniques and the psoas major for CT- and MRI-guided
      techniques. Based on the measurements, we evaluate the trunk's visibility in MR
      and CT images for accurate positioning of the needle. METHODS: A total of 54
      cadavers embalmed with Thiel's method were investigated. The LST's distances to
      the psoas major's medial margin and to the base of the lumbar vertebrae's costal
      process were measured on the levels L2/3, L3/4 and L4/5. The measurements were
      compared to MR and CT images of 20 anonymous patients to identify the LST.
      RESULTS: LST's mean distance to the psoas major was 0.3 mm at L2/3, 3.1 mm at
      L3/4 and 4.6 mm at L4/5. The mean distance to the costal process was 31 mm at
      L2/3, 34 mm at L3/4 and 32.6 mm at L4/5. In both MR and CT imaging, a structure
      could be determined as the LST correlating to the measurements with decreasing
      possible identification from cephalad to caudad levels. CONCLUSIONS: The costal
      process is a usable landmark for fluoroscopic guidance and the psoas major for CT
      and MRI-guided techniques. The LST is clearly visible in MR and CT images, which
      gives both techniques a decisive advantage over fluoroscopy concerning the block
      of the LST due to a visible target.

PMID- 22983732
TI  - Selective self-assembly and characterization of GaN nanopyramids on m-plane
      InGaN/GaN quantum disks.
AB  - Semiconductor nanopyramids (NPs) provide advantages in the development of novel
      functional optoelectronic devices due to their unique size-dependent properties.
      Here we demonstrate a new method for the fabrication of selectively self
      assembled single-crystalline GaN NPs on the m-plane of periodically strained
      GaN/InGaN multiquantum disks embedded in the middle of GaN nanorods. The GaN NPs,
      which have ~100 nm diameters and heights, are observed by scanning electron
      microscopy and their crystalline structure is confirmed by high-resolution
      transmission electron microscopy. Experimental analysis directly reveals the
      strain distribution along the growth direction of the NPs. Cathodoluminescence
      measurements on a single NP show that its emission energy redshifts compared with
      that of bulk GaN, corroborating the results showing the formation of tensile
      strain in the NP. Observations of the uniform distribution and localization of
      these NPs show the possibility of further tuning their size and density by
      controlling periodically strained nanorod surfaces.

PMID- 22983731
TI  - A pathway-based classification of breast cancer integrating data on
      differentially expressed genes, copy number variations and microRNA target genes.
AB  - Breast cancer is a clinically heterogeneous disease characterized by distinct
      molecular aberrations. Understanding the heterogeneity and identifying subgroups
      of breast cancer are essential to improving diagnoses and predicting therapeutic
      responses. In this paper, we propose a classification scheme for breast cancer
      which integrates data on differentially expressed genes (DEGs), copy number
      variations (CNVs) and microRNAs (miRNAs)-regulated mRNAs. Pathway information
      based on the estimation of molecular pathway activity is also applied as a
      postprocessor to optimize the classifier. A total of 250 malignant breast tumors
      were analyzed by k-means clustering based on the patterns of the expression
      profiles of 215 intrinsic genes, and the classification performances were
      compared with existing breast cancer classifiers including the BluePrint and the
      625-gene classifier. We show that a classification scheme which incorporates
      pathway information with various genetic variations achieves better performance
      than classifiers based on the expression levels of individual genes, and propose
      that the identified signature serves as a basic tool for identifying rational
      therapeutic opportunities for breast cancer patients.

PMID- 22983733
TI  - Age-related probability of contralateral processus vaginalis patency in children
      with unilateral inguinal hernia.
AB  - PURPOSE: Contralateral groin exploration with closure of a patent processus
      vaginalis (PPV) in children with a unilateral inguinal hernia remains
      controversial. We aimed to generate precise, age-related probabilities of patency
      of the contralateral processus vaginalis (PV) in infants with a unilateral
      inguinal hernia to guide practice. METHODS: Retrospective review of all
      unilateral laparoscopic inguinal hernia repairs in 5 years to determine patency
      of contralateral PV. Using logistic binomial regression, age-adjusted odds ratio
      (OR), probability of contralateral PPV and number needed to explore (NNE) in
      order to close all PPVs were estimated. RESULTS: Data from 331 children [262
      male, median 3.8 months corrected gestational age (CGA)] were analysed; 160 (48
      %) had a contralateral PPV. In the regression model, CGA is linearly related to
      log[OR] such that for each month increase in CGA, the log[OR] of having a
      contralateral PPV decreased by 0.017 +/- 0.006 (mean +/- SEM; p = 0.005). Gender
      and side of hernia had no significant effect. The probability of contralateral
      PPV is 50 % (NNE = 2) at 8 m CGA, 33 % (NNE = 3) at 49 m and 25 % (NNE = 4) at 72
      m. CONCLUSIONS: These data contribute to our knowledge of the natural history of
      the PV and may help guide the need for contralateral groin exploration in infants
      with inguinal hernia.

PMID- 22983734
TI  - Criteria for the glucagon provocative test in the diagnosis of gastrinoma.
AB  - INTRODUCTION: The glucagon provocative test is useful for the diagnosis of
      gastrinoma. The aim of this study was to determine the criteria for the glucagon
      provocative test. METHODS: This study reviewed 8 patients that underwent the
      glucagon provocative test preoperatively and in whom the diagnosis was confirmed
      as gastrinoma histologically. The glucagon provocative test was performed by
      administering glucagon (20 MUg/kg) intravenously, followed by 20 MUg/kg h for the
      next 30 min, and plasma gastrin levels were measured 3 and 1 min before and 3, 5,
      7, 10, 15, 20, and 30 min after the administration of glucagon. This study
      evaluated the peak value of plasma gastrin and the time required to reach the
      peak. RESULTS: Two of the 8 patients had multiple endocrine neoplasm type 1. The
      basal plasma gastrin levels ranged from 524 to 10,300 pg/ml. The time required to
      reach the peak was 3-10 min for all patients. The increase in the peak from the
      basal value was 235-8,920 pg/ml, and the percentage of increase was 38-337 %.
      CONCLUSIONS: These results suggest that a diagnosis of gastrinoma should thus be
      made when plasma gastrin levels peak within 10 min after glucagon administration,
      with an increase of greater than 200 pg/ml and greater than 35 % of the basal
      value.

PMID- 22983735
TI  - Open-stent grafting with a GORE TAG thoracic endoprosthesis for an extended
      severely atheromatous thoracic aortic aneurysm: report of a case.
AB  - An 82-year-old man with asthma and chronic obstructive pulmonary disease
      experienced sudden back pain. Chest computed tomography (CT) showed a thoracic
      aortic aneurysm (TAA) 63 mm in maximum diameter, with severe atheromas,
      representing "shaggy aorta", extending down to the level of the ninth thoracic
      vertebra. Emergency surgery was necessitated by the impending rupture of the
      aneurysm. The patient underwent successful total arch replacement with open-stent
      grafting using a GORE((r)) TAG((r)) thoracic endoprosthesis. His postoperative
      course was uneventful and there were no neurological complications. We discuss
      the advantages and disadvantages of using the GORE TAG system for an open-stent
      graft.

PMID- 22983736
TI  - Feasibility of laparoscopic gastrectomy for advanced gastric cancer with positive
      peritoneal cytology.
AB  - PURPOSE: The role of gastrectomy for patients with positive peritoneal cytology,
      but a negative macroscopic peritoneal implant (P-/cy+), remains unclear. The aim
      of this study was to evaluate laparoscopic gastrectomy for P-/cy+ patients.
      METHODS: This study reviewed a prospectively maintained gastric cancer database
      of gastric-cancer patients those underwent surgical resection. P-/cy+ gastric
      cancer that had invaded the subserosa, or deeper layers, of the stomach wall
      without distant organ metastases was considered operable in this institution. P
      /cy+ patients underwent either open or laparoscopic gastrectomy with D2
      lymphadenectomy. The short-term results were examined to assess differences in
      outcome between the two groups. RESULTS: Eighteen P-/cy+ patients without distant
      organ metastases underwent surgery between 2000 and 2010. Laparoscopic
      gastrectomy was performed in nine patients and open gastrectomy in nine patients.
      The estimated blood loss was significantly smaller, the resumption of food intake
      earlier, and the length of postoperative hospital stay shorter in the patients
      that underwent laparoscopic gastrectomy than in the patients that underwent open
      gastrectomy. There were no significant differences in the 2-year survival rates
      between the groups. CONCLUSION: Laparoscopic gastrectomy for P-/cy+ patients is a
      minimally invasive and safe oncologic procedure with good short-term results.

PMID- 22983737
TI  - Simple reproducible technique in treatment for osteopetrotic fractures.
AB  - Osteopetrosis is a rare skeletal condition first described by German radiologist
      Heinrich Albers-Schonberg. The most important technical difficulty is drilling
      due to hard bone in patients with osteopetrosis; recommendations have been made
      to use high-speed electric drill bits. But, the unavailability of this special
      drill bit in most of the centres makes the job more difficult. The study was
      conducted from 2009 to 2012; the cases are selected from Outpatients Department
      of Postgraduate Institute of Medical Education and Research. The patients were in
      the age group of 10-50 years with a mean age of 26 years. Five cases were
      included in the study: four patients had subtrochanteric fractures, and one had
      segmental fracture of the humerus. Open reduction and internal fixation was done
      in all the fractures using metal-cutting drill bit. The use of metal-cutting
      drill bit in osteopetrosis not only made our job easy but also prevented thermal
      necrosis of the bone to a large extent. The union rate was 100 % in our series,
      and there was no infection in any of our cases. In the treatment for fractures in
      osteopetrosis, the use of a metal-cutting drill bit along with careful attention
      to drilling technique can help avoid bit breakage and thermal bone injury that
      may produce ring sequestrum or destroy the already scant osteogenic cells.

PMID- 22983738
TI  - An experimental and computational investigation of the post-yield behaviour of
      trabecular bone during vertebral device subsidence.
AB  - Interbody fusion device subsidence has been reported clinically. An enhanced
      understanding of the mechanical behaviour of the surrounding bone would allow for
      accurate predictions of vertebral subsidence. The multiaxial inelastic behaviour
      of trabecular bone is investigated at a microscale and macroscale level. The post
      yield behaviour of trabecular bone under hydrostatic and confined compression is
      investigated using microcomputed tomography-derived microstructural models,
      elucidating a mechanism of pressure-dependent yielding at the macroscopic level.
      Specifically, microstructural trabecular simulations predict a distinctive yield
      point in the apparent stress-strain curve under uniaxial, confined and
      hydrostatic compression. Such distinctive apparent stress-strain behaviour
      results from localised stress concentrations and material yielding in the
      trabecular microstructure. This phenomenon is shown to be independent of the
      plasticity formulation employed at a trabecular level. The distinctive response
      can be accurately captured by a continuum model using a crushable foam plasticity
      formulation in which pressure-dependent yielding occurs. Vertebral device
      subsidence experiments are also performed, providing measurements of the
      trabecular plastic zone. It is demonstrated that a pressure-dependent plasticity
      formulation must be used for continuum level macroscale models of trabecular bone
      in order to replicate the experimental observations, further supporting the
      microscale investigations. Using a crushable foam plasticity formulation in the
      simulation of vertebral subsidence, it is shown that the predicted subsidence
      force and plastic zone size correspond closely with the experimental
      measurements. In contrast, the use of von Mises, Drucker-Prager and Hill
      plasticity formulations for continuum trabecular bone models lead to over
      prediction of the subsidence force and plastic zone. 

PMID- 22983740
TI  - Isolation and characterization of bacteria from mercury contaminated sites in Rio
      Grande do Sul, Brazil, and assessment of methylmercury removal capability of a
      Pseudomonas putida V1 strain.
AB  - Methylmercury (MeHg) is one of the most dangerous heavy metal for living
      organisms that may be found in environment. Given the crescent industrialization
      of Brazil and considering that mercury is a residue of several industrial
      processes, there is an increasing need to encounter and develop remediation
      approaches of mercury contaminated sites. The aim of this study was to isolate
      and characterize methylmercury resistant bacteria from soils and sludge sewage
      from Rio Grande do Sul, Brazil. Sixteen bacteria were isolated from these
      contaminated sites and some isolates were highly resistant to methylmercury (>8.7
      MUM). All the isolates were identified by 16S rDNA. Pseudomonas putida V1 was
      able to volatilize approximately 90 % of methylmercury added to growth media and
      to resist to copper, lead, nickel, chromate, zinc, cobalt, manganese and barium.
      In the presence of high concentrations of methylmercury (12 MUM), cell growth was
      limited, but P. putida V1 was still able to remove up to 29 % of this compound
      from culture medium. This bacterium removed an average of 77 % of methylmercury
      from culture medium with pH in the range 4.0-6.0. In addition, methylmercury was
      efficiently removed (>80 %) in temperature of 21-25  degrees C. Polymerase chain
      reactions indicated the presence of merA but not merB in P. putida V1. The growth
      and ability of P. putida V1 to remove methylmercury in a wide range of pH (4.0
      and 8.0) and temperature (10-35  degrees C), its tolerance to other heavy metals
      and ability to grow in the presence of up to 11.5 MUM of methylmercury, suggest
      this strain as a new potential resource for degrading methylmercury contaminated
      sites.

PMID- 22983739
TI  - Therapies and therapeutic approaches in Congenital Disorders of Glycosylation.
AB  - Inborn errors in glycoconjugate biosynthesis termed 'Congenital Disorders of
      Glycosylation' (CDG) comprise a rapidly expanding group of metabolic diseases in
      man. Up till now more than 60 different inherited disorders in N- and O
      glycosylation pathways have been identified. They affect the biosynthesis of
      glycan moieties linked to proteins as well as lipids. Due to failures in protein
      glycosylation, CDG patients suffer from multi systemic disorders, which mostly
      present with severe psychomotor and mental retardations, muscular impairment,
      ataxia, failure to thrive and developmental delay. Although improved biochemical
      and genetic investigations led to identification of a variety of new molecular
      defects in glycoconjugate biosynthesis, effective therapies for most types of the
      CDG are so far not available. Therefore, intensive investigations on treatment
      options for this group of diseases have been carried out in recent years.

PMID- 22983741
TI  - Polyamines induced by osmotic stress protect Synechocystis sp. PCC 6803 cells and
      arginine decarboxylase transcripts against UV-B radiation.
AB  - The effect of UV-B radiation on growth and polyamines content of Synechocystis
      sp. PCC 6803 subjected to either NaCl or sorbitol stress was investigated. Cells
      could not grow in the presence of 350 mM NaCl or 500 mM sorbitol under normal
      white light. However, cells grown in BG11 under osmotic stress imposed by NaCl or
      sorbitol followed by ultraviolet-B (UV-B) irradiation for 2 h showed higher cell
      density than those under the same condition but no osmotic stress. The
      chlorophyll fluorescence parameter (F(v)/F(m)) also showed an apparent decrease
      upon UV-B irradiation. Intracellular polyamines increased by about 2- and 4-fold
      in NaCl- and sorbitol-stressed cells, respectively. When these cells were
      irradiated with UV-B for 1 h, a further 3-fold increase in polyamines content was
      detected in NaCl-stressed but not sorbitol-stressed cells. Synechocystis cells
      contained adc1 and adc2 genes encoding arginine decarboxylase (ADC) with only
      adc1 showing upregulation by NaCl or sorbitol stress. NaCl- or sorbitol-stressed
      cells contained about 5-fold higher level of adc1 transcript than did the
      unstressed cells after 1-h irradiation with UV-B, suggesting the protection of
      adc1 transcript by accumulated polyamines, due to NaCl or sorbitol stress,
      against UV-B radiation damage. ADC levels as analyzed by Western blot showed
      upregulation by UV-B in NaCl-stressed but not sorbitol-stressed cells.

PMID- 22983742
TI  - Cunninghamella as a microbiological model for metabolism of histamine H(3)
      receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine.
AB  - The aim of the study was to analyze the ability of the microorganism
      Cunninghamella to carry out the biotransformation of 1-[3-(4-tert
      butylphenoxy)propyl]piperidine (DL76) and to compare the obtained results with in
      silico models. Biotransformation was carried out by three strains of filamentous
      fungus: Cunninghamella echinulata, Cunninghamella blakesleeana, and
      Cunninghamella elegans. Most probable direction of DL76 metabolic transition was
      the oxidation of the methyl group in the tert-butyl moiety leading to the
      formation of the metabolite with I degrees  alcohol properties. This kind of
      reaction was conducted by all three strains tested. However, only in the case of
      C. blakesleeana that biotransformation product had a structure of carboxylic
      acid. CYP2C19 was identified by Metasite software to be the isoform of major
      importance in the oxidation process in the tert-butyl moiety of DL76. In silico
      data coincide with the results of experiments conducted in vitro. It was
      confirmed that Cunninghamella fungi are a very good model to study the metabolism
      of xenobiotics. The computational methods and microbial models of metabolism can
      be used as useful tools in early ADME-Tox assays in the process of developing new
      drug candidates.

PMID- 22983743
TI  - Engineering glucosinolates in plants: current knowledge and potential uses.
AB  - Glucosinolates (GSL) and their derivatives are well known for the characteristic
      roles they play in plant defense as signaling molecules and as bioactive
      compounds for human health. More than 130 GSLs have been reported so far, and
      most of them belong to the Brassicaceae family. Several enzymes and transcription
      factors involved in the GSL biosynthesis have been studied in the model plant,
      Arabidopsis, and in a few other Brassica crop species. Recent studies in GSL
      research have defined the regulation, distribution, and degradation of GSL
      biosynthetic pathways; however, the underlying mechanism behind transportation of
      GSLs in plants is still largely unknown. This review highlights the recent
      advances in the metabolic engineering of GSLs in plants and discusses their
      potential applications.

PMID- 22983744
TI  - Effect of alkali pretreatment on the structural properties and enzymatic
      hydrolysis of corn cob.
AB  - An effective alkali pretreatment which affects the structural properties of
      cellulose (corn cob) has been studied. The pretreatment of corn cob was carried
      out with different combinations of alkali at varying temperatures. The most
      effective pretreatment of corn cob was achieved with 1 % alkali at 50  degrees C
      in 4 h. The crystallinity index (CrI) and specific surface area (SSA) of
      untreated corn cob was 39 % and 0.52 m(2)/g wherein after alkali pretreatment CrI
      decreased to 15 % and SSA increased to 3.32 m(2)/g. The fungal organism was
      identified as Penicillium pinophilum on the basis of ITS sequence. At 5 %
      substrate concentration using a complete cellulase from Penicillium pinophilum
      the hydrolysis of untreated corn cob with 5, 10 and 20 FPU/g enzyme loadings were
      11 %, 13 % and 16 %, whereas after alkali treatment the hydrolysis increased to
      78 %, 90 % and 100 %, respectively. Further hydrolytic potential of commercial
      cellulases viz. AccelleraseTM 1,000, Palkofeel-30 and Palkocel-40 were
      investigated under similar conditions.

PMID- 22983745
TI  - High temporal discounters overvalue immediate rewards rather than undervalue
      future rewards: an event-related brain potential study.
AB  - Impulsivity is characterized in part by heightened sensitivity to immediate
      relative to future rewards. Although previous research has suggested that "high
      discounters" in intertemporal choice tasks tend to prefer immediate over future
      rewards because they devalue the latter, it remains possible that they instead
      overvalue immediate rewards. To investigate this question, we recorded the reward
      positivity, a component of the event-related brain potential (ERP) associated
      with reward processing, with participants engaged in a task in which they
      received both immediate and future rewards and nonrewards. The participants also
      completed a temporal discounting task without ERP recording. We found that
      immediate but not future rewards elicited the reward positivity. High discounters
      also produced larger reward positivities to immediate rewards than did low
      discounters, indicating that high discounters relatively overvalued immediate
      rewards. These findings suggest that high discounters may be more motivated than
      low discounters to work for monetary rewards, irrespective of the time of arrival
      of the incentives.

PMID- 22983746
TI  - A call to address complexity in prevention science research.
AB  - The problems targeted by preventive interventions are often complex, embedded in
      multiple levels of social and environmental context, and span the developmental
      lifespan. Despite this appreciation for multiple levels and systems of influence,
      prevention science has yet to apply analytic approaches that can satisfactorily
      address the complexities with which it is faced. In this article, we introduce a
      systems science approach to problem solving and methods especially equipped to
      handle complex relationships and their evolution over time. Progress in
      prevention science may be significantly enhanced by applying approaches that can
      examine a wide array of complex systems interactions among biology, behavior, and
      environment that jointly yield unique combinations of developmental risk and
      protective factors and outcomes. To illustrate the potential utility of a systems
      science approach, we present examples of current prevention research challenges,
      and propose how to complement traditional methods and augment research objectives
      by applying systems science methodologies.

PMID- 22983748
TI  - Elastic rubber band migration into the common bile duct after C-tube drainage.

PMID- 22983747
TI  - Constitutive activation of smoothened leads to impaired developments of postnatal
      bone in mice.
AB  - Sonic hedgehog (Shh) signaling regulates patterning, proliferation, and stem cell
      self-renewal in many organs. Smoothened (Smo) plays a key role in transducing Shh
      signaling into the nucleus by activating a glioma family of transcription
      factors; however, the cellular and molecular mechanisms underlying the role of
      sustained Smo activation in postnatal development are still unclear. In this
      study, we explored the effects of Shh signaling on bone development using a
      conditional knock-in mouse model that expresses a constitutively activated form
      of Smo (SmoM2) upon osteocalcin (OCN)-Cre-mediated recombination (SmoM2; OCN-Cre
      mice). We also evaluated the expression pattern of bone formation-related factors
      in primary calvarial cultures of mutant and control mice. The SmoM2; OCN-Cre
      mutant showed growth retardation and reduction of bone mineral density compared
      to control mice. Constitutively activated SmoM2 also repressed mRNA expression of
      Runx2, osterix, type I collagen, and osteocalcin. Further, sustained SmoM2
      induction suppressed mineralization in calvarial primary osteoblasts cultures,
      whereas such induction did not affect cell proliferation in the mutant cultures
      as compared with SmoM2 only control cultures. These results suggest that
      sustained Smo activation inhibits postnatal development of bone by suppressing
      gene expression of bone formation regulatory factors in mice.

PMID- 22983749
TI  - Clinical and genetic characteristics of congenital sideroblastic anemia:
      comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS).
AB  - Sideroblastic anemia is characterized by anemia with the emergence of ring
      sideroblasts in the bone marrow. There are two forms of sideroblastic anemia,
      i.e., congenital sideroblastic anemia (CSA) and acquired sideroblastic anemia. In
      order to clarify the pathophysiology of sideroblastic anemia, a nationwide survey
      consisting of clinical and molecular genetic analysis was performed in Japan. As
      of January 31, 2012, data of 137 cases of sideroblastic anemia, including 72
      cases of myelodysplastic syndrome (MDS)-refractory cytopenia with multilineage
      dysplasia (RCMD), 47 cases of MDS-refractory anemia with ring sideroblasts
      (RARS), and 18 cases of CSA, have been collected. Hemoglobin and MCV level in CSA
      are significantly lower than those of MDS, whereas serum iron level in CSA is
      significantly higher than those of MDS. Of 14 CSA for which DNA was available for
      genetic analysis, 10 cases were diagnosed as X-linked sideroblastic anemia due to
      ALAS2 gene mutation. The mutation of SF3B1 gene, which was frequently mutated in
      MDS-RS, was not detected in CSA patients. Together with the difference of
      clinical data, it is suggested that genetic background, which is responsible for
      the development of CSA, is different from that of MDS-RS.

PMID- 22983750
TI  - Biological activity of lenalidomide in myelodysplastic syndromes with del5q:
      results of gene expression profiling from a multicenter phase II study.
AB  - In vitro studies suggest that haploinsufficiency is involved in the pathogenesis
      of myelodysplastic syndromes (MDS). In patients with del5q cytogenetic
      abnormality, RPS-14 and microRNAs (miRNAs) play a major role. In a multicenter
      phase II single-arm trial with lenalidomide in anemic primary del5q MDS patients
      with low- or int-1 risk IPSS, biological changes from baseline were investigated.
      Gene expression profiling of selected genes was performed (TaqMan(r) Low Density
      Array Fluidic card, Applied Biosystems PRISM(r) 7900HT) and normalized against
      the expression of the 18S housekeeping gene from a pool of healthy subjects.
      Thirty-two patients were evaluated at baseline and after 3 and 6 months of
      treatment. RPS-14, miR-145, and miR-146 were downregulated at baseline and
      significantly increased during treatment. Nuclear factor kappa B, IL-6,
      interferon regulatory factor-1, IFNgamma-R2, IL-2, and many genes in the
      apoptotic pathways (TNF, IL-1B, and IL-10) were upregulated at baseline and
      significantly downregulated during lenalidomide treatment, while forkhead box P3,
      FAS, IFNgamma, IL-12A, and IL-12B were downregulated at baseline and
      progressively upregulated during treatment. The crucial role of aberrant
      immunological pathways and haploinsufficiency in the pathogenesis of del5q MDS is
      confirmed in the present patient setting. Our results indicate that lenalidomide
      may act through defined immunological pathways in this condition.

PMID- 22983751
TI  - Adolescent patellar osteochondral fracture following patellar dislocation.
AB  - PURPOSE: Patellar dislocations in adolescents may cause osteochondral fractures
      of the patella. The aim of this study was to review the outcomes of adolescent
      patients who underwent surgical intervention for patellar osteochondral fracture
      following patellar dislocation. METHODS: Nine patients who underwent surgery for
      osteochondral fracture of the patella following dislocation were identified
      retrospectively. Following arthroscopic examination, if the fragment was large
      enough to support fixation, headless screws or bioabsorbable pins were used.
      Otherwise, the loose body was excised, and the donor site was managed with a
      microfracture. Postoperatively, patients were assessed using the International
      Knee Documentation Committee (IKDC) and Knee injury and Osteoarthritis Outcome
      Score (KOOS) outcome measures. RESULTS: The average age of the patients was 14.6
      with average follow-up 30.2 months. Four of the nine patients underwent fixation,
      while five patients underwent removal of loose body with microfracture. The
      average defect size in the nonfixation group was 1.2 cm(2) compared with 3.2
      cm(2) in the fixation group. The IKDC scores for fixation and nonfixation groups
      were 63.9 (SD = 18) and 76.1 (SD = 11.7), respectively. The KOOS subscale scores
      for symptoms, function in sports and recreation, and knee-related quality of life
      were higher for the nonfixation group when compared to the fixation group.
      CONCLUSIONS: This is the first known series examining surgical outcomes of
      osteochondral fractures of the patella following patellar dislocations in the
      adolescent population. While patients without fixation were less symptomatic in
      this series, this may be attributable to more severe injuries in patients
      undergoing fracture fixation. LEVEL OF EVIDENCE: Retrospective case series, Level
      IV.

PMID- 22983752
TI  - Anti-inflammatory cytokine profile in early human tendon repair.
AB  - PURPOSE: The aim of this study was to assess inflammation and the presence and
      relative levels of cytokines, which may be involved in regulating early human
      Achilles tendon healing. METHODS: Nine patients with acute Achilles tendon
      rupture were included, operated on and post-operatively immobilized. Two weeks
      post-operatively, microdialysis of the peritendinous interstitial compartment was
      performed in the healing and intact contralateral Achilles tendons.
      Quantification of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma,
      interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70 and IL-17A was accomplished
      using a cytometric bead array. Prostaglandin (PG) E2 levels were measured by
      enzyme immunoassay. RESULTS: None of the patients displayed detectable PGE2
      levels. Pro-inflammatory cytokines were below detection levels (IFNgamma, IL-12,
      and IL-17) or did not differ between injured and control tendons (IL-1beta and
      TNF). Notably, IL-6, IL-8 and IL-10 concentrations in the healing Achilles tendon
      were significantly elevated: 13-fold (p = 0.009), 28-fold (p = 0.02), and 3.7
      fold (p = 0.03), respectively. CONCLUSION: At 2 weeks post-human Achilles tendon
      rupture, healing is characterized by a resolving inflammatory phase and up
      regulation of IL-6, IL-8 and IL-10. The absence of inflammation suggests that at
      this time point, these cytokines may be associated with anti-inflammatory and
      regenerative effects on the tendon healing process.

PMID- 22983753
TI  - Community-responsive interventions to reduce cardiovascular risk in American
      Indians.
AB  - American Indian and Alaska Native (AI/AN) populations bear a heavy burden of
      cardiovascular disease (CVD), and they have the highest rates of risk factors for
      CVD, such as cigarette smoking, obesity, and diabetes, of any U.S. population
      group. Yet, few randomized controlled trials have been launched to test potential
      preventive interventions in Indian Country. Five randomized controlled trials
      were initiated recently in AI/AN communities to test the effectiveness of
      interventions targeting adults and/or children to promote healthy behaviors that
      are known to impact biological CVD risk factors. This article provides a context
      for and an overview of these five trials. The high burden of CVD among AI/AN
      populations will worsen unless behaviors and lifestyles affecting CVD risk can be
      modified. These five trials, if successful, represent a starting point in
      addressing these significant health disparities.

PMID- 22983755
TI  - Post-stroke pneumonia prevention by angiotensin-converting enzyme inhibitors:
      results of a meta-analysis of five studies in Asians.
AB  - INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) are reported to
      reduce the incidence of aspiration pneumonia in hypertensive patients. In this
      study, a metaanalysis was conducted to obtain statistically more reliable
      estimates of outcome. METHODS: The MEDLINE and JMEDICINE databases were searched
      and the following study selection criteria were applied: (1) comparative
      controlled studies identified with the following keywords: drug therapy, ACEI,
      hypertension, swallowing function, dysphagia, stroke, and pneumonia; (2) a
      minimum follow-up period of 6 months; and (3) a minimum number of patients of
      more than 100. Patients with hypertension and a history of stroke or transient
      ischemic attack (TIA) in five controlled studies that reported the incidence of
      pneumonia were included in the analysis. RESULTS: A total of 8,693 post-stroke
      patients were given ACEIs with another antihypertensive agent or placebo as a
      control. In all studies, ACEIs, particularly imidapril, exhibited preventive
      effects equating to a relative risk that ranged from 0.32 to 0.81 compared with
      controls. In the combined studies the overall relative risk of ACEI-treated
      patients versus controls was 0.61 (95% confidence intervals [CI] 0.51-0.75; P <
      0.001). Among Asian patients, the relative risk was 0.42 (95% CI 0.32-0.56; P <
      0.001). Among Japanese patients, an even greater preventive effect was found for
      ACEIs versus other antihypertensives (relative risk: 0.38 [95% CI 0.27-0.54; P <
      0.001]). CONCLUSION: ACEIs appear to be more effective than other
      antihypertensive agents or placebo in reducing pneumonia risk in post-stroke
      patients, especially in Asian populations.

PMID- 22983754
TI  - Dendritic cells in Leishmania major infections: mechanisms of parasite uptake,
      cell activation and evidence for physiological relevance.
AB  - Leishmaniasis is one of the most important infectious diseases worldwide; a
      vaccine is still not available. Infected dendritic cells (DC) are critical for
      the initiation of protective Th1 immunity against Leishmania major. Phagocytosis
      of L. major by DC leads to cell activation, IL-12 release and (cross-)
      presentation of Leishmania antigens by DC. Here, we review the role of Fcgamma
      receptor- and B cell-mediated processes for parasite internalization by DC. In
      addition, the early events after parasite inoculation that consist of mast cell
      activation, parasite uptake by skin-resident macrophages (MPhi), followed by
      neutrophil and monocyte immigration and DC activation are described. All these
      events contribute significantly to antigen processing in infected DC and
      influence resulting T cell priming in vivo. A detailed understanding of the role
      of DC for the development of efficient anti-Leishmania immunity will aid the
      development of potent anti-parasite drugs and/or vaccines.

PMID- 22983756
TI  - Single-agent therapy with sorafenib or 5-FU is equally effective in human
      colorectal cancer xenograft--no benefit of combination therapy.
AB  - BACKGROUND: We initiated this preclinical study in order to analyze the impact of
      sorafenib single treatment versus combination treatment in human colorectal
      cancer. METHODS: The effect of increasing sorafenib doses on proliferation,
      apoptosis, migration, and activation of signal cascades was analyzed in vitro.
      The effect of sorafenib single treatment versus 5-fluorouracil (5-FU) single
      treatment and combination therapy on in vivo proliferation and target cytokine
      receptor/ligand expression was analyzed in a human colon cancer xenograft mouse
      model using HT29 tumor cells. RESULTS: In vitro, SW480 and HT29 cell lines were
      sensitive to sorafenib, as compared to Caco2 and SW620 cell lines, independent of
      the mutation status of K-ras, Raf, PTEN, or PI3K. The effect on migration was
      marginal, but distinct differences in caspases activation were seen. Combination
      strategies were beneficial in some settings (sorafenib + 5-FU; irinotecan) and
      disadvantageous in others (sorafenib + oxaliplatin), depending on the
      chemotherapeutic drug and cell line chosen. Sensitive cell lines revealed a
      downregulation of AKT and had a weak expression level of GADD45beta. In resistant
      cell lines, pp53 and GADD45beta levels decreased upon sorafenib exposure. In
      vivo, the combination treatment of sorafenib and 5-FU was equally effective as
      the respective monotherapy concerning tumor proliferation. Interestingly,
      treatment with either sorafenib or 5-FU resulted in a significant decrease of
      VEGFR1 and PDGFRbeta expression intensity. CONCLUSIONS: In colorectal cancer, a
      sensitivity towards sorafenib exists, which seems similarly effective as a 5-FU
      monotherapy. A combination therapy, in contrast, does not show any additional
      effect.

PMID- 22983758
TI  - Straight needle with fingertip support technique reduces exclusion time during
      bypass (in vitro, in vivo animal study): a technical note.
AB  - BACKGROUND: The duration of exclusion time of recipient artery is an important
      factor in bypass surgery of cerebral revascularization. The longest period of
      exclusion is the suturing time. The fingertip support technique (first published
      in 2006) reduced the physiological tremor to speed up this extra-precise
      microsurgical procedure. The use of a straight needle proved to further decrease
      suturing time during the bypass procedure. METHODS: A straight micro needle was
      added to the fingertip support method for further reduction of exclusion time. A
      comparative study, measuring the duration of suturing time in vitro and in vivo
      for animal cases, was performed. This was a golden opportunity to examine how to
      simplify vascular transposition, using the fingertip support technique and
      straight needle. RESULTS: The average time of the bypass procedure by the novel
      considerations (fingertip support and straight needle) was significantly less
      than the average time by traditional microsurgical support. CONCLUSION: This in
      vitro/in vivo animal study provides evidence of the reduction of the suturing
      time, and thus the exclusion time, by using the fingertip support technique with
      a straight needle in the bypass procedure.

PMID- 22983757
TI  - Short-term outcomes after rehabilitation treatment in patients selected by a
      novel rehabilitation score system (Brusciano score) with or without previous
      stapled transanal rectal resection (STARR) for rectal outlet obstruction.
AB  - PURPOSE: The purpose of this study was to examine short-term outcomes of
      rehabilitation treatment in patients with or without previous stapled transanal
      resection (STARR) for rectal outlet obstruction by using a novel rehabilitation
      score system (Brusciano score). METHODS: This is a retrospective cohort study
      conducted at a single tertiary referral institution including all patients with
      chronic functional constipation admitted to the outpatient unit from 2004 to
      2009. RESULTS: Among 330 consecutive patients, 247 (74.8 %) (204 females and 43
      males) showing a significantly higher rehabilitation score (mean of 15.7 +/- 1.8;
      range, 7-25) than healthy controls (mean, 3.2 +/- 1.2; range 2-6) (p < .0001)
      were selected for rehabilitation. Of the 247 patients evaluated, group A (no
      previous surgery) consisted of 170 patients (53 males; mean age, 44.8 +/- 12.9
      years; range, 19-80) of which 38 presented mixed constipation, whereas group B
      (previous surgery) consisted of 77 patients (18 males; mean age, 47.0 +/- 11.2
      years; range, 22-81). The Brusciano score, Agachan-Wexner score and quality of
      life improved in both groups of patients after treatment. Better improvements of
      Brusciano and Agachan-Wexner scores were observed in patients with previous STARR
      (group B). CONCLUSIONS: The rehabilitation score system employed in this study
      seems to be a useful tool in selecting and assessing the outcome of patients who
      might benefit from rehabilitation treatment. Constipation and quality of life
      were significantly improved by the rehabilitation treatment. Further studies are
      needed to clarify either the impact of rehabilitation treatment on long-term
      outcome of patients treated for rectal outlet obstruction or its role in those
      who develop problems over time.

PMID- 22983759
TI  - Clinical significance and prevalence of anti-Saccharomyces cerevisiae antibody in
      Chinese patients with primary biliary cirrhosis.
AB  - Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) and its
      prevalence in Chinese primary biliary cirrhosis (PBC) patients have not been
      characterized and therefore needs to be defined. Enzyme-linked immunosorbent
      assay was used to test ASCA in sera from 198 PBC patients, 85 patients with other
      liver diseases (OLD) and 35 health controls (HC). Indirect immunofluorescence was
      used to detect anti-mitochondrial antibodies (AMA) in PBC. Results showed that
      the frequency of ASCA in PBC, 29.8 %, was higher than other disease groups. And
      ASCA occurred more frequently in PBC patients with positive anti-gp210 than the
      negative ones. Also, ASCA was detected in 7 out of 15 PBC negative for AMA. Some
      liver-related biochemical indices and inflammatory indices were significantly
      higher in PBC patients with positive ASCA (p < 0.05). In conclusion, the
      prevalence of ASCA in Chinese PBC patients is 29.8 %. PBC patients with positive
      ASCA are associated with more severe liver injury, and ASCA-IgA might be related
      to disease activity of PBC. 

PMID- 22983760
TI  - From Karen to Katie: using baby names to understand cultural evolution.
AB  - How do psychological processes shape how culture evolves? We investigated how a
      cultural item's popularity is shaped by the recent popularity of other items with
      features in common. Specifically, using more than 100 years of first-names data,
      we examined how a name's popularity is influenced by the popularity of that
      name's component phonemes in other names in the previous year. Building on mere
      exposure research, we found that names are more likely to become popular when
      similar names have been popular recently. These effects are nonlinear, however,
      and overpopularity hurts adoption. In addition, these effects vary with phoneme
      position. We demonstrate the causal impact of similarity on cultural success in a
      natural experiment using hurricane names. An exogenous shock to a phoneme's
      frequency, due to the presence of the phoneme in the names of prominent
      hurricanes, boosts the popularity of names that share that phoneme. Taken
      together, our results suggest how the similarity between cultural items affects
      how popular they become and how culture evolves more broadly.

PMID- 22983761
TI  - Basic characteristics of simultaneous color contrast revisited.
AB  - In this article, we present evidence supporting the hypothesis that the local
      mechanism of simultaneous color contrast is the same as the mechanism responsible
      for the crispening effect and the gamut expansion effect. A theoretically
      important corollary of this hypothesis is that the basic characteristics of
      simultaneous contrast are at odds with traditional laws. First, this hypothesis
      implies that the direction of the simultaneous contrast effect in color space is
      given by the vector from surround to target and not--as traditionally assumed--by
      the hue complementary to that of the surround. Second, it implies that the size
      of the simultaneous contrast effect depends on the difference between the target
      and surround colors in a way that challenges Kirschmann's fourth law. The
      widespread belief in the traditional laws, we argue, is due to the confounding
      influence of temporal adaptation.

PMID- 22983762
TI  - Ni(2+) effects on Nicotiana tabacum L. pollen germination and pollen tube growth.
AB  - To investigate the mechanisms of Ni(2+) effects on initiation and maintenance of
      polar cell growth, we used a well-studied model system-germination of angiosperm
      pollen grains. In liquid medium tobacco pollen grain forms a long tube, where the
      growth is restricted to the very tip. Ni(2+) did not prevent the formation of
      pollen tube initials, but inhibited their subsequent growth with IC(50) = 550
      MUM. 1 mM Ni(2+) completely blocked the polar growth, but all pollen grains
      remained viable, their respiration was slightly affected and ROS production did
      not increase. Addition of Ni(2+) after the onset of germination had a
      bidirectional effect on the tubes development: there was a considerable amount of
      extra-long tubes, which appeared to be rapidly growing, but the growth of many
      tubes was impaired. Studying the localization of possible targets of Ni(2+)
      influence, we found that they may occur both in the wall and in the cytoplasm, as
      confirmed by specific staining. Ni(2+) disturbed the segregation of transport
      vesicles in the tips of these tubes and significantly reduced the relative
      content of calcium in the aperture area of pollen grains, as measured by X-ray
      microanalysis. These factors are considered being critical for normal polar cell
      growth. Ni(2+) also causes the deposition of callose in the tips of the tube
      initials and the pollen tubes that had stopped their growth. We can assume that
      Ni(2+)-induced disruption of calcium homeostasis can lead to vesicle traffic
      impairment and abnormal callose deposition and, consequently, block the polar
      growth.

PMID- 22983764
TI  - Introduction: telos, culture, and enhancement technologies.

PMID- 22983763
TI  - Challenging the moral status of blood donation.
AB  - The World Health Organisation encourages that blood donation becomes voluntary
      and unremunerated, a system already operated in the UK. Drawing on public
      documents and videos, this paper argues that blood donation is regarded and
      presented as altruistic and supererogatory. In advertisements, donation is
      presented as something undertaken for the benefit of others, a matter attracting
      considerable gratitude from recipients and the collecting organisation. It is
      argued that regarding blood donation as an act of supererogation is wrongheaded,
      and an alternative account of blood donation as moral obligation is presented.
      Two arguments are offered in support of this position. First, the principle of
      beneficence, understood in a broad consequentialist framework obliges donation
      where the benefit to the recipient is large and the cost to the donor relatively
      small. This argument can be applied, with differing levels of normativity, to
      various acts of donation. Second, the wrongness of free riding requires
      individuals to contribute to collective systems from which they benefit. Alone
      and in combination these arguments present moral reasons for donation, recognised
      in communication strategies elsewhere. Research is required to evaluate the
      potential effects on donation of a campaign which presents blood donation as
      moral obligation, but of wider importance is the recognition that other-regarding
      considerations in relation to our own as well as others' health result in a range
      not only of choices but also of obligations. 

PMID- 22983765
TI  - In sport and social justice, is genetic enhancement a game changer?
AB  - The possibility of genetic enhancement to increase the likelihood of success in
      sport and life's prospects raises questions for accounts of sport and theories of
      justice. These questions obviously include the fairness of such enhancement and
      its relationship to the goals of sport and demands of justice. Of equal interest,
      however, is the effect on our understanding of individual effort, merit, and
      desert of either discovering genetic contributions to components of such effort
      or recognizing the influence of social factors on the development and exercise of
      individual effort. This paper analyzes arguments about genetic enhancement with
      the goal of raising questions about how sport and justice regard unchosen,
      undeserved inequalities and what is assumed to be their opposite-namely, the
      exercise and results of individual effort. It is suggested that contemplating
      enhancement of natural assets previously outside human control may reinforce
      recognition of responsibility to intervene with regard to social advantages so as
      to support individual effort and improve individuals' life prospects.

PMID- 22983766
TI  - Procreative liberty, enhancement and commodification in the human cloning debate.
AB  - The aim of this paper is to scrutinize a contemporary standoff in the American
      debate over the moral permissibility of human reproductive cloning in its
      prospective use as a eugenic enhancement technology. I shall argue that there is
      some significant and under-appreciated common ground between the defenders and
      opponents of human cloning. Champions of the moral and legal permissibility of
      cloning support the technology based on the right to procreative liberty provided
      it were to become as safe as in vitro fertilization and that it be used only by
      adults who seek to rear their clone children. However, even champions of
      procreative liberty oppose the commodification of cloned embryos, and, by
      extension, the resulting commodification of the cloned children who would be
      produced via such embryos. I suggest that a Kantian moral argument against the
      use of cloning as an enhancement technology can be shown to be already implicitly
      accepted to some extent by champions of procreative liberty on the matter of
      commodification of cloned embryos. It is in this argument against commodification
      that the most vocal critics of cloning such as Leon Kass and defenders of cloning
      such as John Robertson can find greater common ground. Thus, I endeavor to
      advance the debate by revealing a greater degree of moral agreement on some
      fundamental premises than hitherto recognized.

PMID- 22983767
TI  - Effect of freezing technology and storage conditions on folate content in
      selected vegetables.
AB  - Folates (B vitamins) are essential for the proper function of many bodily
      processes. Although a rich natural source are vegetables, the literature lacks
      data on the effect of the pre-treatment and freezing technologies used in
      vegetable processing and frozen storage time on the folate content in these
      materials. Moreover, since folates are very unstable nutrients, the amount
      available in processed and stored foods can be significantly lower than in raw
      products. In tested vegetables (green beans, yellow beans, peas, cauliflower,
      broccoli and spinach), one folate form was identified, 5-methyltetrahydrofolate
      (5-CH3-H4folate). It was observed that pre-treatment and freezing technology
      significantly (p < 0.05) decreased 5-CH3-H4folate content only in vegetables with
      the largest degree of fragmentation (cut and briquetted spinach) and the smallest
      size (peas). In all analyzed samples, the 5-CH3-H4folate content decreased with
      the time of frozen storage. In frozen cauliflower, the 5-CH3-H4folate loss
      exceeded 95 % compared to the fresh product just after the third month of frozen
      storage. Meanwhile, in green and yellow beans, significant 5-CH3-H4folate losses
      (at the level of 75 % and 95 %, respectively) were observed no earlier than after
      the 9th month of frozen storage.

PMID- 22983768
TI  - Evaluation of disease activity in rheumatoid arthritis by Routine Assessment of
      Patient Index Data 3 (RAPID3) and its correlation to Disease Activity Score 28
      (DAS28) and Clinical Disease Activity Index (CDAI): an Indian experience.
AB  - Serial objective assessment of disease activity in rheumatoid arthritis (RA) is
      imperative to achieve remission. Routine Assessment of Patient Index Data 3
      (RAPID3), an index without formal joint counts, appears attractive for evaluation
      of disease activity in RA patients in a busy clinical setting. This study aims to
      evaluate correlation and agreement of RAPID3 with Disease Activity Score 28
      (DAS28) and Clinical Disease Activity Index (CDAI) in RA patients. All patients
      completed a Multidimensional Health Assessment Questionnaire (MDHAQ) at each
      visit. A physician/assessor 28-joint count and erythrocyte sedimentation rate
      were completed in 200 literate patients with RA to score DAS28, CDAI, and RAPID3.
      RAPID3 includes the three MDHAQ patient self-report RA core dataset measures for
      physical function, pain, and patient global estimate. Proposed RAPID3 (range, 0
      30) severity categories of high (>12), moderate (6.1-12.0), low (3.1-6.0), and
      near remission (<=3) were compared to DAS28 (0-10) activity categories of high (>
      5.1), moderate (3.21-5.1), low (2.61-3.2), and remission (<= 2.6), and CDAI (0
      76) categories of >22, 10.1-22.0, 2.9-10.0, and <=2.8. Statistical significance
      was analyzed using Spearman correlations, cross-tabulations, and kappa
      statistics. Comparison of RAPID3 with DAS28 and CDAI indicated Spearman rank
      order correlation coefficients for DAS28 with RAPID3 of 0.910, and for CDAI with
      RAPID3 of 0.907, all highly significant (P < 0.001). There was substantial
      agreement between RAPID3 and DAS28 (kappa value = 0.634, P < 0.001) and also
      between RAPID3 and CDAI (kappa value = 0.690, P < 0.001). Overall, 89-94 % of
      patients who met DAS28 or CDAI moderate/high activity criteria met similar RAPID
      severity criteria and 84-88 % who met DAS28 or CDAI remission/low activity
      criteria also met similar RAPID criteria. RAPID3 scores provide similar
      quantitative information to DAS28 and CDAI, and hence, is an informative index
      for evaluation of disease activity in RA in busy clinical settings.

PMID- 22983769
TI  - Survival analysis of late-onset systemic lupus erythematosus: a cohort study in
      China.
AB  - The aim of this study is to explore the survival rate and risk factors of
      mortality in patients with late-onset systemic lupus erythematosus (SLE) in a
      large cohort. Clinical presentations, disease activity, organ damage scores,
      autoantibody profile, and mortality data were obtained retrospectively from late
      onset SLE patients (onset age >=50 years) diagnosed between 1995 and 2009. The
      risk factors of organ damage were evaluated by the chi-square test and logistic
      regression. The cumulative rate of survival was calculated by Kaplan-Meier
      method, and factors predictive of mortality were studied by Cox proportion hazard
      regression model. A total of 158 patients (132 female and 26 male) were studied.
      The average onset age was 58.66 +/- 6.38 years and mean disease duration was
      63.85 +/- 48.17 months. One hundred and four patients had organ damage at the
      time of data analysis. Hematological system and kidney involvement were most
      common. Central nervous system involvement was relatively rare. In univariate
      logistic analysis, associations were found between SLE disease activity index
      (SLEDAI) at diagnosis (OR = 1.133, P = 0.001); renal involvement (OR = 2.441, P =
      0.009) and edema (OR = 2.812, P = 0.003) were associated with organ damage. And
      SLEDAI at diagnosis (OR = 1.103, P = 0.034) was independent factor for organ
      damage in multivariate logistic regression. During the follow-up, 64 patients (51
      female and 13 male) died. Five-, 10-, and 15-year survival rates were 80.4, 56.5,
      and 31.7 %, respectively. Median survival time was 123 months. The analysis of
      Cox proportion hazard regression model showed that age at disease onset (OR =
      1.069, P = 0.002), compliance of medical care (OR = 3.282, P = 0.001), and SLEDAI
      at diagnosis (OR = 1.091, P = 0.003) were independent risk factors of mortality.
      Late-onset SLE has a poor long-term prognosis. Infection is the major cause of
      death in patients with late-onset lupus. Disease activity, medical care, and
      onset age are strongly related to death of late-onset SLE.

PMID- 22983770
TI  - The longer-term effects of Roux-en-Y gastric bypass surgery on sodium excretion.
AB  - BACKGROUND: Obesity is an independent risk factor for hypertension and chronic
      kidney disease. During the first months after bariatric surgery, an improvement
      of sodium excretion has been described. The aim of this work was to study the
      influence of bariatric surgery on sodium excretion at more than a year after the
      intervention. METHODS: Patients who have undergone Roux-en-Y gastric bypass
      (RYGB) and who had collected a 24-h urine sample before surgery more than 12
      months ago were asked to participate. A second 24-h urine sample was collected.
      Blood pressure and weight were measured. The difference in sodium excretion
      before and after surgery was calculated, and the relationship with blood pressure
      and weight loss was investigated. RESULTS: We included 33 patients; the median
      follow-up time was 21 months (range 14-41). Sodium excretion was high before
      surgery (median 195 mmol/day, IQR range 167-247) and decreased by 18 % after
      surgery (median 160 mmol/day, IQR range 118-205, p = 0.015), while there were
      significant improvements in body weight (% EWL 80.9 +/- 21.8), systolic blood
      pressure (126 to 120 mmHg, p = 0.02), and diastolic blood pressure (84 to 77
      mmHg, p = 0.002), even with a reduced number of antihypertensive drugs.
      CONCLUSIONS: After RYGB and considerable weight loss, sodium excretion remains
      high in the longer term. The profound improvement in blood pressure cannot be
      explained by reductions in sodium excretion after RYGB.

PMID- 22983771
TI  - Attitudes towards bariatric surgery in the general public.
AB  - BACKGROUND: Prevalence rates of obesity are still rising. Weight loss surgery
      (WLS) is the most invasive but also most effective treatment option when
      behavioral modification has failed. Research indicates that health care
      professionals hold ambivalent views on bariatric surgery, while views of the
      general public have not yet been investigated. METHODS: In a German
      representative sample of n = 3,003 respondents in a computer-assisted telephone
      interview, n = 1,008 persons were interviewed on their views of the effectiveness
      of bariatric surgery and other interventions for obesity. Also, willingness to
      recommend a treatment was assessed. RESULTS: Lifestyle-based interventions were
      viewed as most effective in terms of weight loss. About 50 % of the population
      stated that WLS is "very effective" while still a quarter of respondents did not
      ascribe effectiveness to WLS. Higher age was associated with lower expectations
      of effectiveness while higher stigmatizing attitudes and genetic attributes for
      obesity were associated with higher expectations of effectiveness. Seventy-two
      percent would not recommend WLS or undergo it, if applicable, themselves. Higher
      educated respondents and those that viewed WLS as effective were more likely to
      recommend WLS. CONCLUSIONS: The German general public seems to be rather cautious
      regarding bariatric surgery. It may be assumed that false beliefs on the
      effectiveness and risk patterns of bariatric surgery are still very common,
      despite rising surgery numbers. Our results further emphasize the need for
      providing evidence-based information on bariatric surgery to the general public.

PMID- 22983772
TI  - Authorships, collaborations, and acknowledgments: on the increasing
      responsibility to report relative contributions.

PMID- 22983773
TI  - Zinc inhibits apoptosis and maintains NEP downregulation, induced by ropivacaine,
      in HaCaT cells.
AB  - Zinc (Zn), a cell-protective metal against various toxic compounds, is the key
      agent for neutral endopeptidase (NEP) functional structure. NEP is a zinc
      metalloenzyme which degrades endogenous opioids and is expressed in human
      keratinocytes (HaCaT). Ropivacaine, a widely used opiate local anaesthetic,
      exerts cell toxic and apoptotic effects against HaCaT cells. The aim of the
      present study is to investigate whether zinc modulates the effects of ropivacaine
      on proliferation, viability, apoptosis and NEP expression in HaCaT cells. To
      investigate the role of ropivacaine in NEP function, HaCaT cells overexpressing
      NEP were generated via cell transfection with plasmids carrying NEP cDNA.
      Ropivacaine's anti-proliferative effect was tested by Neubauer's chamber cell
      counting, and induction of cell death was demonstrated by trypan blue exclusion
      assay. Apoptosis due to ropivacaine was tested via DNA fragmentation and poly-ADP
      ribose-polymerase (PARP) cleavage. NEP and PARP expression was performed by
      western blot analysis. Results showed that zinc (15 MUMU) inhibited proliferation
      and cell death induction by ropivacaine (0.5, 1 and 2 mM) (p < 0.05) as well as
      apoptosis induced by the drug (0.5 and 1 mM) in HaCaT cells. Ropivacaine (1.0,
      2.0 and 5.0 mM) downregulated NEP expression in the presence of zinc (15 MUMU)
      while NEP overexpression enhanced ropivacaine's apoptotic effect. In conclusion,
      the abilities of zinc to inhibit the toxic and apoptotic effects of ropivacaine,
      to maintain NEP downregulation induced by the drug and, consequently, to enhance
      its anaesthetic result suggest that zinc may have a significant role in pain
      management and tissue protection.

PMID- 22983774
TI  - The effects of cobalt on the development, oxidative stress, and apoptosis in
      zebrafish embryos.
AB  - Metal-on-metal hip arthroplasty has been performed with increasing frequency
      throughout the world, particularly in younger and more active patients, including
      women of childbearing age. The potential toxicity of cobalt exposure on fetus is
      concerned since cobalt ions generated by metal-on-metal bearings can traverse the
      placenta and be detected in fetal blood and amniotic fluid. This study examined
      the effects of cobalt exposure on early embryonic development and the mechanisms
      underlying its toxicity. Zebrafish embryos were exposed to a range of cobalt
      concentrations (0-100 mg/L) between 1 and 144 h postfertilization. The survival
      and early development of embryos were not significantly affected by cobalt at
      concentrations <100 MUg/L. However, embryos exposed to higher concentrations
      (>100 MUg/L) displayed reduced survival rates and abnormal development, including
      delayed hatching, aberrant morphology, retarded growth, and bradycardia.
      Furthermore, this study examined oxidative stress and apoptosis in embryos
      exposed to cobalt at concentrations of 0-500 MUg/L. Lipid peroxidation levels
      were increased in cobalt-treated embryos at concentrations of 100 and 500 MUg/L.
      The mRNA levels of catalase, superoxide dismutase 2, p53, caspase-3, and caspase
      9 genes were upregulated in a dose-dependent manner. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling assays also revealed abnormal
      apoptotic signals in the brain, trunk, and tail when treated with 500 MUg/L
      cobalt. These data suggest that oxidative stress and apoptosis are associated
      with cobalt toxicity in zebrafish embryos.

PMID- 22983775
TI  - Pigeons' use of cues in a repeated five-trial-sequence, single-reversal task.
AB  - We studied behavioral flexibility, or the ability to modify one's behavior in
      accordance with the changing environment, in pigeons using a reversal-learning
      paradigm. In two experiments, each session consisted of a series of five-trial
      sequences involving a simple simultaneous color discrimination in which a
      reversal could occur during each sequence. The ideal strategy would be to start
      each sequence with a choice of S1 (the first correct stimulus) until it was no
      longer correct, and then to switch to S2 (the second correct stimulus), thus
      utilizing cues provided by local reinforcement (feedback from the preceding
      trial). In both experiments, subjects showed little evidence of using local
      reinforcement cues, but instead used the mean probabilities of reinforcement for
      S1 and S2 on each trial within each sequence. That is, subjects showed remarkably
      similar behavior, regardless of where (or, in Exp. 2, whether) a reversal
      occurred during a given sequence. Therefore, subjects appeared to be relatively
      insensitive to the consequences of responses (local feedback) and were not able
      to maximize reinforcement. The fact that pigeons did not use the more optimal
      feedback afforded by recent reinforcement contingencies to maximize their
      reinforcement has implications for their use of flexible response strategies
      under reversal-learning conditions.

PMID- 22983776
TI  - Seeking connections, creating movement: the power of altruistic action.
AB  - Participation of older people in designing and improving the care and services
      provided in residential care settings is limited. Traditional forms of democratic
      representation, such as client councils, and consumer models are management
      driven. An alternative way of involving older people in the decisions over their
      lives, grounded in notions of care ethics and deliberative democracy, was
      explored by action research. In line with this tradition older people engage in
      collective action to enhance the control over their lives and those of others. In
      this article the theoretical background of altruistic action is presented and
      illustrated by a case example of a group of older women who changed the food
      policies within their residential home. Altruistic action is the joint and
      coordinated action by a group of clients based on their agenda. Such action is
      given in by a shared dissatisfaction and search for connections. Altruistic
      action may enhance the sense of self, belonging and ownership, and create a
      transformative movement enhancing the wellbeing and community life in residential
      settings. 

PMID- 22983778
TI  - Temporary elimination of orthostatic hypotension by norepinephrine infusion.
AB  - A cardinal manifestation of chronic autonomic failure is neurogenic orthostatic
      hypotension (OH), which often is associated with supine hypertension, posing a
      therapeutic dilemma. We report here success in a first step toward development of
      a "prosthetic baroreceptor system" to maintain blood pressure during orthostasis
      without worsening supine hypertension. In all of four patients with neurogenic
      OH, titrated i.v. NE infusion kept directly recorded intra-arterial pressure at
      or above baseline during progressive head-up tilt. We conclude that titrated i.v.
      NE infusion temporarily eliminates OH.

PMID- 22983779
TI  - Management of gastric perforations during laparoscopic gastric banding.
AB  - BACKGROUND: Gastric perforations are one of the intraoperative complications of
      laparoscopic gastric banding (LAGB). Delayed diagnosis can increase the mortality
      and morbidity rates. METHODS: Retrospective analysis of surgery outcome and long
      term follow-up of the patients with gastric perforations during primary LAGB and
      revisional band procedures was performed. RESULTS: Twenty-four patients with
      gastric perforations were identified during 15 years of LAGB surgeries. Half of
      these had primary LAGB and half had revisional procedures (five emergent and
      seven elective). Gastric tear was found at surgery in 19 patients; the band was
      preserved and LAGB was completed in 18 of these. Five patients had delayed
      diagnosis and underwent re-exploration 24-72 h after surgery. During the surgery,
      23 anterior, 8 posterior, 1 esophageal, and 1 small bowel tears were found.
      Laparoscopic repair was successful in 19 (83%) cases. The mean surgery time and
      mean hospital stay were 56.3 min and 7.8 days, respectively. Morbidity and
      mortality rates were 25 and 4.1%, respectively. Two patients underwent later band
      replacement following removal. Band erosion was observed in one patient. At least
      17 patients had no complications during mean follow-up of 52.2 months.
      CONCLUSIONS: Band preservation is recommended following primary repair of gastric
      tear. Early intra- and postoperative diagnosis of gastric tear in LAGB is
      essential for successful management of this iatrogenic injury and decreases
      occurrence of complications.

PMID- 22983780
TI  - Measuring the health-related quality of life (HRQoL) of young children in
      resource-limited settings: a review of existing measures.
AB  - PURPOSE: This review sought to identify and summarize the instruments adapted or
      developed for measuring HRQoL among young children (<8 years) living in resource
      limited settings. METHODS: A review of the literature was conducted in two
      phases. Phase one searched the PubMed, PsycInfo, Web of Knowledge (Web of
      Science), African Index Medicus, and SocINDEX databases and identified widely
      used child HRQoL instruments. Phase two reviewed the articles using the selected
      HRQoL instruments and extracted information on their use in resource-limited
      settings including adaption processes. RESULTS: Seven instruments were identified
      that measured the HRQoL of young children. Six had been used in resource-limited
      settings. Of the 452 articles using these instruments, a total of 23 (5 %)
      studies used one of the identified HRQoL instruments in a resource-limited
      setting. Among these studies, 39 % employed an adaptation process for the use of
      that instrument. No instruments had been developed specifically for measuring the
      HRQoL of young children in resource-limited settings. CONCLUSIONS: If pediatric
      HRQoL instruments are to be used in resource-limited settings, it is critical
      that they be developed and adequately adapted to those settings. Only then will
      interventions lead to larger increases in the overall HRQoL and well-being of
      children.

PMID- 22983781
TI  - Validation of the WHOQOL-BREF quality of life questionnaire for general use in
      New Zealand: confirmatory factor analysis and Rasch analysis.
AB  - PURPOSE: The present study validated the abbreviated version of the World Health
      Organization Quality of Life (WHOQOL-BREF) questionnaire for general use in New
      Zealand. METHODS: A random postal sample from the national electoral roll was
      used, and 808 questionnaires were returned. Psychometric properties of the
      instrument were assessed, including tests of the four-domain factor structure
      using confirmatory factor analysis and Rasch analysis. RESULTS: Goodness-of-fit
      from the confirmatory factor analysis were good, and the overall conclusion of
      the Rasch analysis supported the confirmatory factor analysis (CFA) findings
      after dealing with problems of threshold ordering, local dependency, and
      differential item functioning (DIF). CONCLUSIONS: The WHOQOL-BREF is valid for
      general use in New Zealand. In the future work, the WHOQOL-BREF domain scores
      should either be analyzed using non-parametric statistics or data should be
      fitted to the Rasch model to derive interval person estimates.

PMID- 22983783
TI  - Deafness in children: a national survey of aetiological investigations.
AB  - OBJECTIVE: The aim of this study was to obtain national data regarding adherence
      to national guidelines for aetiological investigations for hearing loss in
      children and highlight any variations in practice. Information was also collected
      on possible factors affecting lack of adherence. DESIGN: An online questionnaire
      based on the national guidelines for aetiological investigations for deafness was
      designed. SETTING: The questionnaire was distributed to the leads of all the
      Newborn Hearing Screening Programme (NHSP) sites across England through the
      Medical Research Council Hearing & Communication Group. PARTICIPANTS: The
      questionnaire was sent to 100 recipients; from this 52 responses were obtained.
      OUTCOME MEASURES: Variability in the investigations offered for hearing loss.
      RESULTS: There was a 52% response rate. Analysis of the responses showed that
      audiovestibular physicians and paediatricians in audiology were more likely than
      other specialists to request level 1 investigations (investigations that are
      recommended to be offered in all cases). Respondents from London and the North
      West were more likely to request level 1 investigations compared with those from
      other regions. In all, 14 of the 19 audiovestibular physicians and paediatricians
      in audiology requested level 1 investigations routinely, but only 11 of 33 from
      other specialties did likewise. Of the 20 respondents from London and the
      Northwest, 15 requested level 1 investigations routinely, whereas only 10 of the
      32 respondents from the other regions did the same. The difference was
      statistically significant in both cases. The geographical variation was specially
      marked for family audiograms and MRI. CONCLUSIONS: There is significant variation
      from the national guidelines in requesting aetiological investigations for
      permanent hearing impairment (PHI) in children, depending on the specialty of the
      clinician and the geographical region, these variations appear partly to be due
      to the availability of local resources but also due to lack of awareness of the
      importance of some investigations.

PMID- 22983782
TI  - Early rehabilitation in critical care (eRiCC): functional electrical stimulation
      with cycling protocol for a randomised controlled trial.
AB  - INTRODUCTION: Intensive care-acquired weakness is a common problem, leads to
      significant impairment in physical functioning and muscle strength, and is
      prevalent in individuals with sepsis. Early rehabilitation has been shown to be
      safe and feasible; however, commencement is often delayed due to a patient's
      inability to co-operate. An intervention that begins early in an intensive care
      unit (ICU) admission without the need for patient volition may be beneficial in
      attenuating muscle wasting. The eRiCC (early rehabilitation in critical care)
      trial will investigate the effectiveness of functional electrical stimulation
      assisted cycling and cycling alone, compared to standard care, in individuals
      with sepsis. METHODS AND ANALYSIS: This is a single centre randomised controlled
      trial. Participants (n=80) aged >=18 years, with a diagnosis of sepsis or severe
      sepsis, who are expected to be mechanically ventilated for >=48 h and remain in
      the intensive care >=4 days will be randomised within 72 h of admission to (1)
      standard care or (2) intervention where participants will receive functional
      electrical muscle stimulation-assisted supine cycling on one leg while the other
      leg undergoes cycling alone. Primary outcome measures include: muscle mass
      (quadriceps ultrasonography; bioelectrical impedance spectroscopy); muscle
      strength (Medical Research Council Scale; hand-held dynamometry) and physical
      function (Physical Function in Intensive Care Test; Functional Status Score in
      intensive care; 6 min walk test). Blinded outcome assessors will assess measures
      at baseline, weekly, at ICU discharge and acute hospital discharge. Secondary
      measures will be evaluated in a nested subgroup (n=20) and will consist of
      biochemical/histological analyses of collected muscle, urine and blood samples at
      baseline and at ICU discharge. ETHICS AND DISSEMINATION: Ethics approval has been
      obtained from the relevant institution, and results will be published to inform
      clinical practice in the care of patients with sepsis to optimise rehabilitation
      and physical function outcomes. TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry ACTRN12612000528853.

PMID- 22983784
TI  - A metric-based analysis of structure and content of telephone consultations of
      final-year medical students in a high-fidelity emergency medicine simulation.
AB  - OBJECTIVES: In this study we aimed to analyse the structure and content of
      telephone consultations of final-year medical students in a high-fidelity
      emergency medicine simulation. The purpose was to identify any areas of
      deficiency within structure and content in the effective transfer of clinical
      information via the telephone of final-year medical students. DESIGN: An
      educational study. SETTING: Simulation centre in a medical school. PARTICIPANTS:
      113 final-year medical students. PRIMARY AND SECONDARY OUTCOMES: The primary
      outcome was to analyse the structure and content of telephone consultations of
      final-year medical students in a high-fidelity emergency medicine simulation. The
      secondary outcome was to identify any areas of deficiency within structure and
      content in the effective transfer of clinical information via the telephone of
      final-year medical students. RESULTS: During phone calls to a senior colleague
      30% of students did not positively identify themselves, 29% did not identify
      their role, 32% did not positively identify the recipient of the phone call, 59%
      failed to positively identify the patient, 49% did not read back the
      recommendations of their senior colleague and 97% did not write down the
      recommendations of their senior colleague. CONCLUSIONS: We identified a
      deficiency in our students skills to communicate relevant information via the
      telephone, particularly failure to repeat back and write down instructions. We
      suggest that this reflects a paucity of opportunities to practice this skill in
      context during the undergraduate years. The assumption that this skill will be
      acquired following qualification constitutes a latent error within the healthcare
      system. The function of undergraduate medical education is to produce graduates
      who are fit for purpose at the point of graduation.

PMID- 22983785
TI  - Do statins interfere with lifestyle intervention in the prevention of diabetes in
      primary healthcare? One-year follow-up of the FIN-D2D project.
AB  - OBJECTIVES: To examine whether the use of statins is associated with the
      incidence of type 2 diabetes (T2D) and changes in glucose metabolism among
      individuals at high risk for T2D participating in 1-year lifestyle intervention
      in primary healthcare setting. DESIGN: Prospective follow-up study. SETTING: In
      all, 400 primary healthcare centres and occupational healthcare clinics in
      Finland. PARTICIPANTS: We screened altogether 10 149 individuals at increased
      risk for T2D; of these, 2798 non-diabetic individuals verified by a 2 h glucose
      tolerance test participated in the 1-year follow-up. INTERVENTIONS: Lifestyle
      intervention (individual and/or group-based counselling). PRIMARY OUTCOME
      MEASURES: Incidence of T2D and fasting and 2 h glucose measured at baseline and
      follow-up. RESULTS: A total of 484 individuals (17.3%) used statins at the
      baseline. Of them 31 (7.5%) developed T2D during the follow-up, compared to 126
      (6.5%) of statin non-users (OR 1.17, 95% CI 0.78 to 1.76, p=0.442).
      Interestingly, fasting glucose increased by 0.08 mmol/l in statin users, but
      remained unchanged in non-users, the difference being 0.074 mmol/l (95% CI 0.014
      to 0.134) and remained significant even after adjustment for age, sex, baseline
      fasting glucose, the presence of cardiovascular disease (CVD), use of
      antihypertensive and/or coronary artery disease medication, weight and 1-year
      weight change (adjusted p=0.042). CONCLUSIONS: The incidence of T2D did not
      differ between the statin users and non-users. The finding that fasting glucose
      slightly increased in statin users in spite of lifestyle interventions suggests
      the view that the use of statins might have unfavourable effects on glucose
      metabolism and that statins might hamper beneficial effects of lifestyle
      intervention in people at high risk of T2D.

PMID- 22983786
TI  - Identifying early warning signs for diagnostic errors in primary care: a
      qualitative study.
AB  - OBJECTIVE: We investigate the mechanisms of diagnostic error in primary care
      consultations to detect warning signs for possible error. We aim to identify
      places in the diagnostic reasoning process associated with major risk indicators.
      DESIGN: A qualitative study using semistructured interviews with open-ended
      questions. SETTING: A 2-month study in primary care conducted in Oxfordshire, UK.
      PARTICIPANTS: We approached about 25 experienced general practitioners by email
      or word of mouth, 15 volunteered for the interviews and were available at a
      convenient time. INTERVENTION: Interview transcripts provided 45 cases of error.
      Three researchers searched these independently for underlying themes in relation
      to our conceptual framework. OUTCOME MEASURES: Locating steps in the diagnostic
      reasoning process associated with major risk of error and detecting warning signs
      that can alert clinicians to increased risk of error. RESULTS: Initiation and
      closure of the cognitive process are most exposed to risk of error. Cognitive
      biases developed early in the process lead to errors at the end. These warning
      signs can be used to alert clinicians to the increased risk of diagnostic error.
      Ignoring red flags or critical cues was related to processes being biased through
      the initial frame, but equally well, it could be explained by knowledge gaps.
      CONCLUSIONS: Cognitive biases developed at the initial framing of the problem
      relate to errors at the end of the process. We refer to these biases as warning
      signs that can alert clinicians to the increased risk of diagnostic error. We
      conclude that lack of knowledge is likely to be an important factor in diagnostic
      error. Reducing diagnostic errors in primary care should focus on early and
      systematic recognition of errors including near misses, and a continuing
      professional development environment that promotes reflection in action to
      highlight possible causes of process bias and of knowledge gaps.

PMID- 22983787
TI  - A clinical audit of changes in suicide ideas with internet treatment for
      depression.
AB  - OBJECTIVES: To examine reductions in suicidal ideation among a sample of patients
      who were prescribed an internet cognitive behavior therapy (iCBT) course for
      depression. DESIGN: Effectiveness study within a quality assurance framework.
      SETTING: Primary care. PARTICIPANTS: 299 patients who were prescribed an iCBT
      course for depression by primary care clinicians. INTERVENTION: Six lesson, fully
      automated cognitive behaviour therapy course delivered over the internet. PRIMARY
      OUTCOME: suicidal ideation as measured by question 9 on the Patient Health
      Questionnaire (PHQ-9). RESULTS: Suicidal ideation was common (54%) among primary
      care patients prescribed iCBT treatment for depression but dropped to 30% post
      treatment despite minimal clinician contact and the absence of an intervention
      focused on suicidal ideation. This reduction in suicidal ideation was evident
      regardless of sex and age. CONCLUSIONS: The findings do not support the exclusion
      of patients with significant suicidal ideation.

PMID- 22983788
TI  - Reducing postnatal depression, anxiety and stress using an infant sleep
      intervention.
AB  - OBJECTIVE: To examine the psychological well-being of mothers following
      participation in a behavioural modification programme previously shown to improve
      infant sleep. DESIGN, SETTING AND PARTICIPANTS: A 45 min consultation with either
      a general practitioner (GP) or trained nurse providing verbal and written
      information describing sleep physiology in infants and strategies to improve
      infant sleep. Eighty mothers of infants 6-12 months of age with established
      infant sleep problems at a single general practice, Adelaide, South Australia.
      MAIN OUTCOME MEASURES: The Depression Anxiety Stress Scale 21 (DASS21)
      immediately prior to the first consultation and again at follow-up approximately
      3 weeks later. The number of infant nocturnal awakenings requiring parental
      support was also reported by mothers on both occasions. RESULTS: All measures of
      maternal well-being and infant nocturnal awakenings improved significantly. The
      mean number of maximum nocturnal awakenings decreased from 5.0 to 0.5 (mean
      difference 4.4, 95% CI 3.4 to 5.5). All measures of DASS21 improved
      significantly. The mean total DASS21 decreased from 29.1 to 14.9 (mean decrease
      14.2, 95% CI 10.2 to 18.2); mean depression decreased from 7.9 to 2.8 (mean
      difference 5.2, 95% CI 3.7 to 6.7); mean anxiety decreased from 4.6 to 2.6 (mean
      difference 2.0, 95% CI 0.7 to 3.2); mean stress decreased from 16.6 to 9.5 (mean
      difference 7.0, 95% CI 5.1 to 9.0). The proportion of mothers assessed as having
      any degree of depression decreased by 85% from 26/80 (32.5%) to 4/80 (5%).
      CONCLUSIONS: The number of nocturnal awakenings requiring parental support among
      infants aged 6-12 months significantly decreased following a single consultation
      on infant sleep physiology and teaching behavioural strategies to improve sleep.
      Significant improvements in maternal stress, anxiety and depression were also
      observed.

PMID- 22983789
TI  - Neuroprotective effects of tert-butylhydroquinone on paraquat-induced
      dopaminergic cell degeneration in C57BL/6 mice and in PC12 cells.
AB  - The present study was aimed at determining the role of paraquat (PQ) in the
      activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway
      and the possible neuroprotective effects of tert-butylhydroquinone (tBHQ)
      pretreatment on PQ-induced neurodegeneration in vivo and in vitro. 7 mg/kg PQ
      treatment of male C57BL/6 mice caused decreased spontaneous locomotor activity,
      decreased tyrosine hydroxylase (TH)-positive neurons, increased terminal
      deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL)
      positive cells in the substantia nigra, as well as increased protein levels of
      both nuclear Nrf2 and HO-1. In PQ-treated mice, pretreatment with 1 % tBHQ (w/w)
      significantly attenuated impairments in behavioral performance, decreased TH
      positive neurons, and increased TUNEL-positive cells in the substantia nigra, as
      well as increased protein expression of both nuclear Nrf2 and HO-1. Pretreatment
      with 40 MUM tBHQ protected PC12 cells against 100 and 300 MUM PQ-mediated
      cytotoxicity. The dual-luciferase reporter gene also revealed that the
      transcriptional activation of HO-1 gene expression of the antioxidant responsive
      element via Nrf2 occurred as a consequence of 100 and 300 MUM PQ exposure.
      Collectively, these results clearly indicated for the first time that the Nrf2/HO
      1 pathway in the substantia nigra was activated by PQ, and pretreatment with tBHQ
      conferred neuroprotection against PQ-induced Parkinsonism presumably by
      increasing Nrf2 and HO-1 expression.

PMID- 22983790
TI  - Experiences of microsurgical reconstruction for variant hepatic artery in living
      donor liver transplantation.
AB  - There is an emergent need for improving the microsurgical technique of variant
      arterial anastomosis to reduce the often seen surgery-related complications. We
      describe in this article our experience in improving this technique, in 73 living
      donor liver grafts (64 right lobes, 9 left lobes) in patients with end-stage
      liver disease during living donor liver transplantation. The hepatic arteries
      were evaluated preoperatively with computed tomography and magnetic resonance
      angiography. In this series, 13 grafts (17.80 %) with variant hepatic artery were
      conducted arterioplasty on a back-table under a loupe or a high-power microscope,
      which included one recipient in situ interposition vessel graft of recipient
      proper hepatic artery for artery reconstruction. The back-table reconstruction
      time was 16 +/- 5.6 min. No arterial thrombosis was found in these cases during
      the 6-month postoperative follow-up. On the basis of our experience, we suggest
      that back-table microsurgical plasty for graft with arterial variation should be
      applied to minimize operative difficulties and to avoid arterial complications in
      living donor liver transplantation.

PMID- 22983791
TI  - Level of deprivation does not affect degree of discounting in pigeons.
AB  - Two experiments tested the effects of food deprivation on discounting in pigeons.
      An adjusting-amount procedure was used to estimate the subjective value of food
      at delays ranging from 1 to 24 s. Experiment 1 compared pigeons' discounting of
      delayed food reinforcers at 75 %-80 % and 90 %-95 % of free-feeding weight.
      Experiment 2 compared discounting under 1- and 23-h food deprivation. In both
      experiments at both deprivation levels, discounting was well described by the
      hyperboloid discounting function. No systematic effect of level of deprivation on
      degree of discounting was observed in either experiment. This finding is
      consistent with the view that pigeons' choices are controlled by the relative,
      rather than the absolute, value of reinforcers.

PMID- 22983792
TI  - Ultrasonic alignment of bio-functionalized magnetic beads and live cells in PDMS
      micro-fluidic channel.
AB  - In this work, we demonstrated the alignment of polystyrene latex microspheres
      (diameter of 1 ~45 MUm), bio-functionalized superparamagnetic beads (diameter 2.8
      MUm), and live cells (average diameter 1 ~2 MUm) using an ultrasonic standing
      wave (USW) in a PDMS microfluidic channel (330 MUm width) attached on a Si
      substrate for bio-medical applications. To generate a standing wave inside the
      channel, ultrasound of 2.25 MHz resonance frequency (for the channel width) was
      applied by two ultrasound transducers installed at both sides of the channel
      which caused the radiation force to concentrate the micro-particles at the single
      pressure nodal plane of USW. By increasing the frequency to the next resonance
      condition of the channel, the particles were concentrated in dual nodal planes.
      Migration time of the micro-particles towards the single nodal plane was recorded
      as 108 s, 17 s, and 115 s for polystyrene particles of 2 MUm diameter, bio
      functionalized magnetic beads, and live cells, respectively. These successful
      alignments of the bio-functionalized magnetic beads along the desired part of the
      channel can enhance the performance of a sensor which is applicable for the bio
      hybrid system and the alignment of live cells without any damage can be used for
      sample pre-treatment for the application of lab-on-a-chip type bioassays.

PMID- 22983793
TI  - Fibroblasts influence muscle progenitor differentiation and alignment in contact
      independent and dependent manners in organized co-culture devices.
AB  - Myoblasts are precursor muscle cells that lie nascent to mature skeletal muscle.
      Once muscle is damaged, these cells migrate, fuse, and regenerate the muscle
      tissue. It is known that skeletal muscle can partially regenerate in vivo after
      muscle tissue damage. However, this regeneration does not always occur,
      especially in more severe injuries. Cellular therapy using tissue-engineering
      approaches has been shown to improve organ repair and function. To exploit
      potential benefits of using cell therapy as an avenue for skeletal muscle repair,
      it is important to understand the cellular dynamics underlying skeletal myocyte
      formation and growth. Cardiac fibroblasts have been shown to have a major
      influence on cardiomyocyte function, repair, and overall spatial distribution.
      However, little is known regarding fibroblasts' role on skeletal myocyte
      function. In this study, we utilized a reconfigurable co-culture device to
      understand the contact and paracrine effects of fibroblasts on skeletal myocyte
      alignment and differentiation using murine myoblast and fibroblast cell lines. We
      demonstrate that myotube alignment is increased by direct contact with
      fibroblasts, while myotube differentiation is reduced both in the gap and contact
      configurations with fibroblasts after 6 days of co-culture. Furthermore,
      neutralizing antibodies to FGF-2 can block these effects of fibroblasts on
      myotube differentiation and alignment. Finally, bi-directional signaling is
      critical to the observed myoblast-fibroblast interactions, since conditioned
      media could not reproduce the same effects observed in the gap configuration.
      These findings could have direct implications on cell therapies for repairing
      skeletal muscle, which have only utilized skeletal myoblasts or stem cell
      populations alone.

PMID- 22983794
TI  - PET/MR for therapy response evaluation in malignant lymphoma: initial experience.
AB  - OBJECT: To evaluate the feasibility of positron emission tomography/magnetic
      resonance imaging (PET/MR) with (18)fluoro-2-deoxyglucose (FDG) for therapy
      response evaluation of malignant lymphoma. MATERIALS AND METHODS: Nine patients
      with malignant lymphoma who underwent FDG-PET/MR before and after chemotherapy
      were included in this retrospective study. Average time between the two scans was
      70 days. The scans were evaluated independently by two nuclear medicine
      physicians. The Ann Arbor classification was used to describe lymphoma stage.
      Furthermore, the readers also rated PET image quality using a five point scale.
      Weighted kappa (kappa) was used to calculate interrater agreement. RESULTS: The
      initial scan showed foci of increased FDG uptake in all patients, with Ann Arbor
      stage varying between I and IV. In the follow-up examination, all but one patient
      showed complete response to chemotherapy. PET image quality was rated as very
      good or excellent for all scans. Interrater agreement was excellent regarding Ann
      Arbor stage (kappa = 0.97) and good regarding image quality (kappa = 0.41).
      CONCLUSION: PET/MR shows promising initial results for therapy response
      evaluation in lymphoma patients.

PMID- 22983796
TI  - Redescription of Chabaudacuaria multispinosa (Perez Vigueras, 1938) n. g., n.
      comb. (Nematoda: Spirurida: Acuariidae) based on specimens from Ardea herodias L.
      and Nyctanassa violacea (L.) (Ardeidae) in Florida.
AB  - Chabaudacuaria n. g. is erected, as monotypic, for C. multispinosa (Perez
      Vigueras, 1938) n. comb. (Spirurida: Acuariidae) [syns Cheilospirura multispinosa
      Perez Vigueras, 1938; Acuaria multispinosa (Perez Vigueras, 1938) Yamaguti,
      1961]. This species, a parasite of various ardeid birds, is redescribed by means
      of light and scanning electron microscopy based on material from great blue
      herons Ardea herodias L. and yellow-crowned night herons Nyctanassa violacea (L.)
      in Florida, USA. Chabaudacuaria n. g. resembles Acuaria Bremser, 1811,
      Cheilospirura Diesing, 1861, Skrjabinocerca Schikhobalova, 1930 and Xenocordon
      Mawson, 1982 in its straight cordons which do not anastomose. However, it can be
      distinguished from them by the didelphic-prodelphic uterus and the absence of
      caudal alae in the males. In the pattern of its cordons (consisting of a row of
      plates and a longitudinal ridge) and the absence of an area rugosa, the new genus
      is similar to Chevreuxia Seurat, 1918, Syncuaria Gil'bert, 1927, Aviculariella
      Wehr, 1931, Skrjabinocara Kurashvili, 1940, Decorataria Sobolev, 1949 and
      Desportesius Chabaud & Campana, 1949, which are characterised by anastomosing
      cordons. The didelphic-prodelphic female reproductive system of Chabaudacuaria is
      intermediate between the didelphic-amphidelphic uterus of Chevreuxia and the
      monodelphic-prodelphic uterus of Syncuaria, Aviculariella, Skrjabinocara,
      Desportesius and Decorataria. Therefore, the straight and non-anastomosing
      cordons are considered to be autapomorphic for Chabaudacuaria.

PMID- 22983795
TI  - p53 contributes to quercetin-induced apoptosis in human rheumatoid arthritis
      fibroblast-like synoviocytes.
AB  - In the present study, we sought to explore the mechanism of quercetin-induced
      apoptosis in rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs). DNA
      fragmentation assay was used to detect quercetin-induced apoptosis in RAFLSs. The
      cleavages of caspase-3 and caspase-9 and the accumulation of cytosolic cytochrome
      C were measured by western blot in quercetin-treated RAFLSs. Mitochondrial
      membrane potential was tested by flow cytometry. Small interfering RNAs were used
      to knock down the expression of protein 53 (p53) and analyze the role of p53 in
      quercetin-induced apoptosis in RAFLSs. DNA fragmentation assay showed that
      quercetin dose-dependently elevated the apoptosis of RAFLSs, accompanying with
      enhanced caspase-3 and caspase-9 cleavages. Moreover, quercetin caused a
      concentration-dependent loss of mitochondrial membrane potential and cytochrome c
      release to cytosol and also decreased Bcl-2/Bax ratio, indicating that quercetin
      induced apoptosis is through mitochondrial pathway. Quercetin also elevated p53
      phosphorylation at ser15. Pretreatment with pifithrin-alpha, a p53 inhibitor,
      significantly diminished p53 phosphorylation at the concentration of 30 MUM and
      abrogated quercetin-induced apoptosis in a dose-dependent manner. Quercetin
      induced apoptosis was also significantly blocked by p53 silencing, further
      suggesting the involvement of p53 in quercetin-induced apoptosis in RAFLSs. Our
      study indicated that quercetin-induced apoptosis of RAFLSs is through
      mitochondrial pathway, in which p53 plays an important role.

PMID- 22983797
TI  - A checklist of new species of Henneguya Thelohan, 1892 (Myxozoa: Myxosporea,
      Myxobolidae) described between 2002 and 2012.
AB  - A checklist of the new species of Henneguya described since 2002 (43 species) is
      presented. Included are the main features of each species, the type-host, the
      type-locality and the original references. In addition, accession numbers to
      sequences in GenBank are indicated whenever possible.

PMID- 22983798
TI  - A revision of the chigger mite genus Paratrombicula Goff & Whitaker, 1984 (Acari:
      Trombiculidae), with the description of two new species.
AB  - The monotypic chigger mite genus Paratrombicula Goff & Whitaker, 1984 is expanded
      to include five species. Two new species of chiggers, parasitising iguanid
      lizards in Chile, Paratrombicula chilensis n. sp. and P. goffi n. sp., are
      described, and two species, P. neuquenensis (Goff & Gettinger, 1995) n. comb. and
      Paratrombicula plaumanni (Brennan & Jones, 1964) n. comb., are transferred to
      this genus from Parasecia Loomis, 1966 and Neotrombicula Hirst, 1925,
      respectively. A key to the species of Paratrombicula is presented.

PMID- 22983799
TI  - Female morphology of Philometra hyderabadensis Rasheed, 1963 (Nematoda:
      Philometridae), a little-known parasite of the catfish Wallago attu Bloch &
      Schneider in India, as revealed by SEM observations.
AB  - The female morphology of the nematode Philometra hyderabadensis Rasheed, 1963
      (Philometridae) is described based on subgravid specimens found in the abdominal
      cavity and intestine of the catfish (wallago) Wallago attu Bloch & Schneider from
      the Purna River and Yeldari Reservoir, Parbhani District, Maharashtra State,
      India collected in August 2010 and January 2011, respectively. Light and scanning
      electron microscopical examination made it possible to study in detail the
      morphology of this little-known species. In contrast to the original species
      description, the female cephalic end was found to bear 10 small cephalic
      papillae: four submedian double papillae of the external circle and six single
      papillae of the internal circle, of which two are lateral and four submedian. The
      anterior end of the oesophagus is only slightly inflated and there are three
      distinct oesophageal teeth protruding from the mouth. Previously, P.
      hyderabadensis had been known only from a single female specimen collected in
      Hyderabad, India and deposited in the Natural History Museum, London.
      Consequently, the present finding represents the second documented record of this
      species, 50 years after its original description. Philometra suraiyae Kalyankar,
      1971 is considered a junior synonym of P. hyderabadensis.

PMID- 22983800
TI  - Three new species of picobiine mites (Acari: Syringophilidae) parasitising
      African flycatchers (Aves: Muscicapidae).
AB  - Three new species of quill mites of the subfamily Picobiinae Johnston & Kethley,
      1973 (Acari: Syringophilidae) are described from African flycatchers
      (Passeriformes: Muscicapidae): Picobia cichladusa n. sp. on Cichladusa arquata
      Peters and P. myrmecocichla n. sp. on Myrmecocichla arnotti (Tristram), both from
      Tanzania, and P. echo n. sp. on Cossypha heuglini Hartlaub from the Democratic
      Republic of the Congo.

PMID- 22983801
TI  - A new species of Philometra Costa, 1845 (Nematoda: Philometridae) from the
      freshwater fish (red piranha) Pygocentrus nattereri Kner (Characidae) in
      Amazonia, Brazil.
AB  - A new nematode species, Philometra nattereri n. sp. (Philometridae), is described
      from female specimens found in the oculo-orbits and nasal cavity of the red
      piranha Pygocentrus nattereri Kner (Characiformes: Characidae) from five lakes in
      Central Amazonia, Brazil, collected in 2008 and 2009 (overall prevalence 12%,
      intensity 1-3 nematodes per fish). Based on light and scanning electron
      microscopical examination, the new species differs from most other congeners
      parasitising freshwater fishes in that its oesophageal gland extends anteriorly
      far anterior to the level of the nerve-ring, in the presence of 14 small cephalic
      papillae arranged in two circles and in having two minute caudal projections.
      This is the first species of Philometra Costa, 1845 reported from fishes of the
      family Characidae and the second valid species of this genus parasitic in
      freshwater fishes of Brazil and South America.

PMID- 22983802
TI  - A new species of Asthenocotyle Robinson, 1961 (Monogenea: Microbothriidae), a
      skin parasite of the great lanternshark Etmopterus princeps Collett from the
      Azores, with a redescription of A. kaikourensis Robinson, 1961 and observations
      on A. taranakiensis Beverley-Burton, Klassen & Lester, 1987.
AB  - Asthenocotyle azorensis n. sp. (Monogenea: Microbothriidae) is described from the
      dermal denticles of the great lanternshark Etmopterus princeps Collett off the
      Azores. The type-species of the genus, A. kaikourensis Robinson, 1961, is
      redescribed and additional observations are made on A. taranakiensis Beverley
      Burton, Klassen & Lester, 1987. The generic diagnosis is revised. The new species
      is distinguished from its two congeners by the large size of the pharynx and
      fewer testes. The ejaculatory bulb of A. kaikourensis is much larger than those
      of A. taranakiensis and A. azorensis and is supplied with many ducts from an
      extensive field of male accessory gland-cells located outside the genital pouch
      and extending posteriorly to the region of the germarium and external seminal
      vesicle. Asthenocotyle taranakiensis is distinguished from the other two species
      by its copulatory sclerite, which forms a double loop, although this may not be
      the case when the copulatory organ is extended. The bodies of A. azorensis and A.
      kaikourensis are similar in shape, with the maximum width approximately 37% and
      25%, respectively, of the total length from the anterior end. In addition to the
      relatively small size of the genital pouch and ejaculatory bulb in A. azorensis
      and A. taranakiensis, the vaginal opening is adjacent to the common genital
      opening. In A. kaikourensis, the vaginal opening is distant from and posterior to
      the common genital opening. The functional morphology of the copulatory organ of
      A. azorensis is considered. The relative importance, for the taxonomy of
      microbothriids, of the number of testes versus the anatomy of the copulatory
      complex is discussed.

PMID- 22983803
TI  - A monogenean fish parasite, Gyrodactylus chileani n. sp., belonging to a novel
      marine species lineage found in the South-Eastern Pacific and the Mediterranean
      and North Seas.
AB  - Gyrodactylus chileani n. sp. is the first Gyrodactylus species reported from
      Chile. It is an ectoparasite living on fins and skin of a small fish, the Chilean
      tidal pond dweller Helcogrammoides chilensis (Cancino) (Perciformes:
      Tripterygiidae). A phylogenetic analysis based on 5.8S+ITS2 of rDNA placed the
      new species close to marine Gyrodactylus species found in Europe: G. orecchiae
      Paladini, Cable, Fioravanti, Faria, Cave & Shinn, 2009 on gilthead seabream
      Sparus aurata L. from the Adriatic and Tyrrhenian Sea fish farms (Perciformes:
      Sparidae), and an undescribed species on the black goby Gobius niger L. from the
      North Sea (Perciformes: Gobiidae). A morphological description of the latter
      species is unavailable. These geographically distant parasite samples on
      different host families form a new well supported Gyrodactylus orecchiae lineage.
      Using molecular phylogenetics, it is shown that the marine species groups of
      Gyrodactylus may have a worldwide distribution.

PMID- 22983804
TI  - High serum palmitic acid is associated with low antiviral effects of interferon
      based therapy for hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection alters fatty acid synthesis and metabolism in
      association with HCV replication. The present study examined the effect of serum
      fatty acid composition on interferon (IFN)-based therapy. Fifty-five patients
      with HCV were enrolled and received IFN-based therapy. Patient characteristics,
      laboratory data (including fatty acids), and viral factors that could be
      associated with the anti-HCV effects of IFN-based therapy were evaluated. The
      effects of individual fatty acids on viral replication and IFN-based therapy were
      also examined in an in-vitro system. Multivariate logistic regression analysis
      showed that the level of serum palmitic acid before treatment and HCV genotype
      were significant predictors for rapid virological response (RVR), early
      virological response (EVR), and sustained virological response (SVR). High levels
      of palmitic acid inhibited the anti-HCV effects of IFN-based therapy. HCV
      replication assays confirmed the inhibitory effects of palmitic acid on anti-HCV
      therapy. The concentration of serum palmitic acid is an independent predictive
      factor for RVR, EVR, and SVR in IFN-based antiviral therapy. These results
      suggest that the effect of IFN-based antiviral therapy in patients with HCV
      infection might be enhanced by treatment that modulates palmitic acid levels.

PMID- 22983805
TI  - Relevance of motion-related assessment metrics in laparoscopic surgery.
AB  - INTRODUCTION: Motion metrics have become an important source of information when
      addressing the assessment of surgical expertise. However, their direct
      relationship with the different surgical skills has not been fully explored. The
      purpose of this study is to investigate the relevance of motion-related metrics
      in the evaluation processes of basic psychomotor laparoscopic skills and their
      correlation with the different abilities sought to measure. METHODS: A framework
      for task definition and metric analysis is proposed. An explorative survey was
      first conducted with a board of experts to identify metrics to assess basic
      psychomotor skills. Based on the output of that survey, 3 novel tasks for
      surgical assessment were designed. Face and construct validation was performed,
      with focus on motion-related metrics. Tasks were performed by 42 participants (16
      novices, 22 residents, and 4 experts). Movements of the laparoscopic instruments
      were registered with the TrEndo tracking system and analyzed. RESULTS: Time, path
      length, and depth showed construct validity for all 3 tasks. Motion smoothness
      and idle time also showed validity for tasks involving bimanual coordination and
      tasks requiring a more tactical approach, respectively. Additionally, motion
      smoothness and average speed showed a high internal consistency, proving them to
      be the most task-independent of all the metrics analyzed. CONCLUSION: Motion
      metrics are complementary and valid for assessing basic psychomotor skills, and
      their relevance depends on the skill being evaluated. A larger clinical
      implementation, combined with quality performance information, will give more
      insight on the relevance of the results shown in this study.

PMID- 22983806
TI  - Prediction of breast resection weight in reduction mammaplasty based on 3
      dimensional surface imaging.
AB  - Prediction of resection weight (RW) in reduction mammaplasty is helpful in
      achieving breast symmetry and in fulfilling the stringent reimbursement
      requirements of health insurance companies. Current breast volume estimations are
      largely based on surgeon's experience, which are partially unreliable and often
      cumbersome to obtain. Therefore, this study aims to develop a formula to predict
      RW based on 3D surface imaging. A total of 68 breasts were treated with bilateral
      T-scar, and 40 breasts were treated with bilateral or unilateral vertical-scar
      reduction mammaplasty. Linear distances and volume measurements were assessed 3
      dimensionally preoperatively and 6 months postoperatively. Significant
      correlations between the RW and the calculated preoperative breast volume (rho =
      0.804) and the sternal notch to nipple distance (rho = 0.839) were found in both
      techniques (P < .001). Regression equations with the RW were performed to derive
      prediction formulas. Surgeons may benefit from the formulas in terms of
      improvement in preoperative planning, dealing with insurance coverage questions,
      and optimizing patient consultation.

PMID- 22983807
TI  - Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and
      titanium dioxide (TiO(2)) nanoparticles.
AB  - The aim of this study is to uncover the size influence of poly (lactic-co
      glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles on their
      potential cytotoxicity. PLGA and TiO(2) nanoparticles of three different sizes
      were thoroughly characterized before in vitro cytotoxic tests which included
      viability, generation of reactive oxygen species (ROS), mitochondrial
      depolarization, integrity of plasma membrane, intracellular calcium influx and
      cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7
      cells and BEAS-2B cells after cells were incubated with PLGA or TiO(2)
      nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly
      lethal toxicity up to a concentration of 300 MUg/ml, the TNF-alpha release after
      the stimulation of PLGA nanoparticles should not be ignored especially in
      clinical applications. Relatively more toxic TiO(2) nanoparticles triggered cell
      death, ROS generation, mitochondrial depolarization, plasma membrane damage,
      intracellular calcium concentration increase and size-dependent TNF-alpha
      release, especially at a concentration higher than 100 MUg/ml. These cytotoxic
      effects could be due to the size-dependent interaction between nanoparticles and
      biomolecules, as smaller particles tend to adsorb more biomolecules. In summary,
      we demonstrated that the ability of protein adsorption could be an important
      paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for
      low toxic nanomaterials such as PLGA and TiO(2) nanoparticles.

PMID- 22983808
TI  - Antimicrobial prescribing in nursing homes in Finland: results of three point
      prevalence surveys.
AB  - PURPOSE: The purpose of this study was to analyse the Finnish European
      Surveillance of Antimicrobial Consumption (ESAC) nursing home (NH) point
      prevalence surveys' (PPSs) data in detail, i.e. to evaluate the variability in
      the prevalence of antimicrobial prescription between NHs and its relationship to
      resident characteristics. METHODS: All residents present in NHs for >= 24 h and
      receiving systemic antimicrobials on the day of the survey were included. Data on
      antimicrobials and their indications (prophylaxis or treatment, type of
      infection) were collected. RESULTS: Three PPSs were performed: eight NHs
      participated in April and November 2009 and nine in May-September 2010. In total,
      there were 5,691 eligible residents (range by survey, 1,706-2,320; range by NH,
      60-688), 716 (12.6 %; range by NH, 3.2-33.3 %) of which received at least one
      antimicrobial and 40 residents received two. The most common indication was
      prophylaxis (487/5,691, 8.6 %), mainly for urinary tract infection (UTI)
      (460/487, 94.5 %). Of the residents, 269/5,691 (4.7 %, range by NH, 1.5-6.0 %)
      were on antimicrobial treatment. UTI (119/269; 44.2 %) was the most common
      indication for treatment. Methenamine (306/756, 40.5 %) was the most commonly
      used antimicrobial, followed by trimethoprim (13.6 %) and pivmecillinam (11.0 %).
      In the eight NHs participating in all three surveys, the prevalence of residents
      receiving antimicrobials decreased from 16.6 to 9.7 %. CONCLUSIONS: Antimicrobial
      use was common in NHs in Finland and most were used for UTI prophylaxis and
      treatment. The usage, however, varied among NHs and tended to decrease during the
      surveys. NHs may benefit from antimicrobial stewardship interventions focused on
      UTI.

PMID- 22983809
TI  - Immune-related antigens, surface molecules and regulatory factors in human
      derived mesenchymal stromal cells: the expression and impact of inflammatory
      priming.
AB  - Based on their ability to regulate immune responses, MSCs are considered to be
      potential candidates for managing immune-mediated diseases in the context of
      immune therapy. AT and WJ are considered valuable alternatives for BM as a source
      of MSCs. A detailed and comparative characterization of the immunological profile
      of MSCs derived from different sources, as well as an understanding of their
      responsiveness under certain circumstances, such as inflammation, is required to
      facilitate efficient and well-designed clinical studies. Flow cytometric analyses
      revealed clear differences among MSC types concerning the expression of the
      endothelial (e.g., CD31, CD34, CD144 and CD309) and stromal (e.g., CD90 and
      CD105) associated markers. Regardless of their source, MSCs did not express any
      of the known hematopoietic markers. All MSCs were uniformly positive for HLA-ABC
      and lacked the expression of HLA-DR and the co-stimulatory molecules (e.g., CD40,
      CD80, CD86, CD134 and CD252) required for full T-cell activation. Tissue-specific
      MSCs presented a modulated expression of cell adhesion molecules that is
      important for their cellular interactions. MSCs exhibited several surface (e.g.,
      CD73, HLA-G, HO-1 and CD274) and soluble (e.g., HGF, PGE2 and IGFBP-3)
      immunoregulatory molecules. According to these immunological profiles, the
      present work provides evidence that the source from which MSCs are derived is
      important for the design of MSC-based immunointervention approaches. In light of
      these observations, we may suggest that WJ-MSCs appear to be the most attractive
      cell population to use in immune cellular therapy when immunosuppressive action
      is required.

PMID- 22983810
TI  - Socio-economic inequalities in health, habits and self-care during pregnancy in
      Spain.
AB  - Socioeconomic disadvantage can be harmful for mother's health and can influence
      child's health long term. The aim of this study is to analyse social inequalities
      between pregnant women from four INMA (INfancia y Medio Ambiente) cohorts. The
      analysis included 2,607 pregnant women recruited between 2004 and 2008 from four
      INMA cohorts. Data on maternal characteristics were collected through two
      questionnaires completed in the first and third trimester of pregnancy. The
      relationship between socioeconomic status (SES) and maternal health, dietary
      intake, lifestyle habits and self-care related variables was modelled using
      logistic regression analysis. 33.5 % of women had a university level of education
      and 47 % had high occupational class. Women with higher SES reported healthier
      habits, fewer complications during pregnancy, better weight gain control and
      attended more prenatal appointments than women with lower SES. The risk of
      sedentary behaviour and passive smoking was higher among women with a lower level
      of education (OR = 1.7, 95 % CI 1.3-2.2 and OR = 1.6, 95 % CI 1.2-2.3,
      respectively) and with less skilled occupations (OR = 1.7, 95 % CI 1.4-2.0 and OR
      = 1.2, 95 % CI 1.0-1.5, respectively). Although both SES indicators-occupation
      and education-act as social determinants of diet, occupation was a more powerful
      determinant than education. For other lifestyle and self-caring variables,
      education was a more powerful predictor than occupation. Social inequalities were
      observed in health, habits and self-care during pregnancy. Proper care during
      pregnancy requires the control of common clinical variables and the knowledge of
      socioeconomic conditions of the pregnant women. 

PMID- 22983811
TI  - Stress first myocardial perfusion imaging: is it time to put to rest the "rest
      first" strategy for most patients?

PMID- 22983812
TI  - Retroviral-vector-mediated gene therapy to mucopolysaccharidosis I mice improves
      sensorimotor impairments and other behavioral deficits.
AB  - Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to alpha-L
      iduronidase (IDUA) deficiency that results in the accumulation of
      glycosaminoglycans (GAG). Systemic gene therapy to MPS I mice can reduce
      lysosomal storage in the brain, but few data are available regarding the effect
      upon behavioral function. We investigated the effect of gene therapy with a long
      terminal-repeat (LTR)-intact retroviral vector or a self-inactivating (SIN)
      vector on behavioral function in MPS I mice. The LTR vector was injected
      intravenously to 6-week-old MPS I mice, and the SIN vector was given to neonatal
      or 6-week-old mice. Adult-LTR, neonatal-SIN, and adult-SIN-treated mice achieved
      serum IDUA activity of 235 +/- 20 (84-fold normal), 127 +/- 10, and 71 +/- 7
      U/ml, respectively. All groups had reduction in histochemical evidence of
      lysosomal storage in the brain, with the adult-LTR group showing the best
      response, while adult-LTR mice had reductions in lysosomal storage in the cristae
      of the vestibular system. Behavioral evaluation was performed at 8 months.
      Untreated MPS I mice had a markedly reduced ability to hold onto an inverted
      screen or climb down a pole. LTR-vector-treated mice had marked improvements on
      both of these tests, whereas neonatal-SIN mice showed improvement in the pole
      test. We conclude that both vectors can reduce brain disease in MPS I mice, with
      the LTR vector achieving higher serum IDUA levels and better correction.
      Vestibular abnormalities may contribute to mobility problems in patients with MPS
      I, and gene therapy may reduce symptoms.

PMID- 22983813
TI  - The effects of health shocks on employment and health insurance: the role of
      employer-provided health insurance.
AB  - Employment-contingent health insurance (ECHI) has been criticized for tying
      insurance to continued employment. Our research sheds light on two central issues
      regarding employment-contingent health insurance: whether such insurance "locks"
      people who experience a health shock into remaining at work; and whether it puts
      people at risk for insurance loss upon the onset of illness, because health
      shocks pose challenges to continued employment. We study how men's dependence on
      their own employer for health insurance affects labor supply responses and health
      insurance coverage following a health shock. We use the Health and Retirement
      Study (HRS) surveys from 1996 through 2008 to observe employment and health
      insurance status at interviews 2 years apart, and whether a health shock occurred
      in the intervening period between the interviews. All employed married men with
      health insurance either through their own employer or their spouse's employer,
      interviewed in at least two consecutive HRS waves with non-missing data on
      employment, insurance, health, demographic, and other variables, and under age 64
      at the second interview are included in the study sample. We then limited the
      sample to men who were initially healthy. Our analytical sample consisted of
      1,582 men of whom 1,379 had ECHI at the first interview, while 203 were covered
      by their spouse's employer. Hospitalization affected 209 men with ECHI and 36 men
      with spouse insurance. A new disease diagnosis was reported by 103 men with ECHI
      and 22 men with other insurance. There were 171 men with ECHI and 25 men with
      spouse employer insurance who had a self-reported health decline. Labor supply
      response differences associated with ECHI-with men with health shocks and ECHI
      more likely to continue working-appear to be driven by specific types of health
      shocks associated with future higher health care costs but not with immediate
      increases in morbidity that limit continued employment. Men with ECHI who have a
      self-reported health decline are significantly more likely to lose health
      insurance than men with insurance through a spouse. With the passage of health
      care reform, the tendency of men with ECHI as opposed to other sources of
      insurance to remain employed following a health shock may be diminished, along
      with the likelihood of losing health insurance.

PMID- 22983814
TI  - Vitamin B12 level in peripheral arterial disease.
AB  - Hyperhomocysteinemia is considered a risk factor for atherosclerosis.
      Methyltetrahydrofolate reductase (MTHFR) gene mutation and low level of plasma
      vitamin B12 and folate could take part in the etiology of peripheral arterial
      disease (PAD). We examined whether plasma vitamin B12 and folate levels and MTHFR
      C677T polymorphism are associated with the risk of PAD. The study comprised 293
      patients (107 females, 186 males, mean age of 66 +/- SEM0.7 years) and 293 sex
      matched control subjects (mean age of 62 +/- SEM0.8 years). We also determined
      plasma lipid profile, hs-CRP, creatinine, vitamin B12, folate and total
      homocysteine (tHcy) for all patients and controls. Odds ratios were non
      significant for different genotypes of MTHFR-C677T polymorphism. There was a
      significant lower level of vitamin B12 in PAD patients. 43 and 25 % of patient
      and control populations were in the lowest quartile of vitamin B12 (<188 pmol/L),
      respectively. Plasma level of vitamin B12 in the lowest quartile significantly
      increased tHcy level in PAD patients, and it was independent of plasma folate
      level. Low level of plasma vitamin B12 was independently associated with
      hyperhomocysteinemia in PAD patients. The prevalence of the MTHFR-C677T mutation
      was not significantly different in patients with PAD compared with controls.

PMID- 22983815
TI  - Participation of 47C>T SNP (Ala-9Val polymorphism) of the SOD2 gene in the
      intracellular environment of human peripheral blood mononuclear cells with and
      without lipopolysaccharides.
AB  - The outcome of sepsis occurs due to influence of environmental and genetic
      factors besides genes variants whose expression support its outcome or not.
      Oxidative stress is associated to the pathogenicity of sepsis, occurring when
      there is a reactive species overproduction associated with inflammation. The aim
      of this study was to characterize the cellular redox status of human peripheral
      blood mononuclear cells (PBMCs) with either -9Ala (AA) or -9Val (VV) SOD2
      genotypes and evaluate their response to oxidative stress induced by
      lipopolysaccharide (LPS). The PBMCs were isolated from the blood of 30 healthy
      human volunteers (15 volunteers for each allele) and the following assays were
      performed: antioxidant enzyme activities (superoxide dismutase; catalase;
      glutathione peroxidase), total radical-trapping antioxidant parameter, non
      enzymatic antioxidant capacity (total antioxidant reactivity), and quantification
      of conjugated dienes (lipid peroxidation). At basal conditions (i.e., not
      stimulated by LPS), cells from 47C allele carriers showed higher activities of
      CAT and SOD, as well as higher TAR compared to 47T allele. However, when 47CC
      cells were challenged with LPS, we observed a higher shift toward a pro-oxidant
      state compared to 47TT cells. The CAT activity and lipid peroxidation were
      increased in cells with both alleles, but SOD activity increased significantly
      only in 47TT cells. These results demonstrate that SOD2 polymorphisms are
      associated with different cellular redox environments at both basal and LPS
      stimulated states, and identification of this polymorphism may be important for a
      better understanding of pro-inflammatory conditions.

PMID- 22983817
TI  - Bupropion: efficacy and safety in the treatment of depression.

PMID- 22983816
TI  - eNOS polymorphism associated with metabolic syndrome in children and adolescents.
AB  - We investigated whether genetic polymorphisms in the endothelial nitric oxide
      (eNOS) gene (T(786)C in the promoter region, Glu298Asp in exon 7, and 4b/4a in
      intron 4) or eNOS haplotypes are associated with metabolic syndrome (MetS) in
      obese children and adolescents. We studied 242 subjects: 108 healthy (controls),
      64 normotensive obese, and 70 obese children and adolescents with MetS. Genotypes
      were determined by Taqman((r)) allele discrimination assay and real-time
      polymerase chain reaction (PCR), and PCR followed by fragment separation by
      electrophoresis. We compared the distribution of eNOS genotypes, alleles, and
      haplotypes in the three groups of subjects. The CC genotype for the T(786)C
      polymorphism was more common in the MetS group than in the control group (OR =
      3.27; CI 1.81-9.07; P < 0.05). However, we found no significant differences in
      the distribution of eNOS haplotypes (P > 0.00625; P for significance after
      correction for multiple comparisons). Our findings suggest that while eNOS
      haplotypes are not relevant, the CC genotype for the T(786)C polymorphism is
      associated with MetS in obese children and adolescents. Further studies examining
      interactions of eNOS haplotypes with environmental factors and other genetic
      markers are warranted.

PMID- 22983818
TI  - Human genome-specific real-time PCR method for sensitive detection and
      reproducible quantitation of human cells in mice.
AB  - Xenotransplantation of human cells into immunodeficiency mice has been frequently
      used to study stem cells in tissue repair and regeneration and cancer cell
      metastasis. However, a sensitive and reproducible method to quantify cell
      engraftment lacks. Here, we developed a Real-Time PCR-based method which
      facilitated consistent detection and quantification of small amounts of human
      cells distributed in mouse organs after infusion. The principle of the method was
      to directly detect a humans-specific sequence in the human-murine genomic DNA
      mixture. In a mouse myocardial infarction model, the Real-Time PCR-based method
      consistently determined the amounts of human mesenchymal stem cells (hMSCs)
      engrafted into the heart and other organs 7 days after infusion of as little as
      2.5 * 10(5) cells, indicating a high sensitivity, and the amounts of hMSCs
      detected in mice highly correlated to the numbers of hMSCs transplanted.
      Importantly, different from previous PCR-based methods, our method produced
      highly consistent and reproducible results. The reliability of the method was
      further proven by parallel analyses of DiI-labeled hMSCs in tissue sections and
      in single cell suspensions of mice. Our data show that the present human genomic
      DNA-specific primers-based Real-Time PCR method is sensitive and highly
      reproducible in determining the amount of xenotransplanted human cells in murine
      tissues.

PMID- 22983819
TI  - Total portal robotic pneumonectomy.
AB  - Robotic pulmonary lobectomies have been reported to be technically and
      oncologically achievable; however, only three robotic pneumonectomy cases have
      been described. Two of them used a mini thoracotomy. We describe one case of a
      total portal robotic pneumonectomy without utility incision. We describe the step
      by-step process. 

PMID- 22983820
TI  - Music therapy modulates fronto-temporal activity in rest-EEG in depressed
      clients.
AB  - Fronto-temporal areas process shared elements of speech and music.
      Improvisational psychodynamic music therapy (MT) utilizes verbal and musical
      reflection on emotions and images arising from clinical improvisation. Music
      listening is shifting frontal alpha asymmetries (FAA) in depression, and
      increases frontal midline theta (FMT). In a two-armed randomized controlled trial
      (RCT) with 79 depressed clients (with comorbid anxiety), we compared standard
      care (SC) versus MT added to SC at intake and after 3 months. We found that MT
      significantly reduced depression and anxiety symptoms. The purpose of this study
      is to test whether or not MT has an impact on anterior fronto-temporal resting
      state alpha and theta oscillations. Correlations between anterior EEG, Montgomery
      Asberg Depression Rating Scale (MADRS) and the Hospital Anxiety and Depression
      Scale-Anxiety Subscale (HADS-A), power spectral analysis (topography, means,
      asymmetry) and normative EEG database comparisons were explored. After 3 month of
      MT, lasting changes in resting EEG were observed, i.e., significant absolute
      power increases at left fronto-temporal alpha, but most distinct for theta (also
      at left fronto-central and right temporoparietal leads). MT differed to SC at F7
      F8 (z scored FAA, p < .03) and T3-T4 (theta, p < .005) asymmetry scores, pointing
      towards decreased relative left-sided brain activity after MT; pre/post increased
      FMT and decreased HADS-A scores (r = .42, p < .05) indicate reduced anxiety after
      MT. Verbal reflection and improvising on emotions in MT may induce neural
      reorganization in fronto-temporal areas. Alpha and theta changes in fronto
      temporal and temporoparietal areas indicate MT action and treatment effects on
      cortical activity in depression, suggesting an impact of MT on anxiety reduction.

PMID- 22983822
TI  - The employment costs of caregiving in Norway.
AB  - Informal eldercare is an important pillar of modern welfare states and the
      ongoing demographic transition increases the demand for it while social trends
      reduce the supply. Substantial opportunity costs of informal eldercare in terms
      of forgone labor opportunities have been identified, yet the effects seem to
      differ substantially across states and there is a controversy on the effects in
      the Nordic welfare states. In this study, the effects of informal care on the
      probability of being employed, the number of hours worked, and wages in Norway
      are analyzed using data from the Life cOurse, Generation, and Gender survey. New
      and previously suggested instrumental variables are used to control for the
      potential endogeneity existing between informal care and employment-related
      outcomes. In total, being an informal caregiver in Norway is found to entail
      substantially less costs in terms of forgone formal employment opportunities than
      in non-Nordic welfare states.

PMID- 22983821
TI  - The association of ACE, ACTN3 and PPARA gene variants with strength phenotypes in
      middle school-age children.
AB  - The aim of the study was to determine the association between ACE I/D, ACTN3
      R577X and PPARA intron 7 G/C gene polymorphisms and strength-related traits in
      457 middle school-age children (219 boys and 238 girls; aged 11 +/- 0.4 years).
      The assessment of different phenotypes was conducted with a number of performance
      tests. Gene polymorphisms were determined by PCR. The ACE D allele was associated
      with high results of standing long-jump test in boys [II 148.3 (16.3) cm, ID
      152.6 (19.6) cm, DD 158.2 (19.1) cm; P = 0.037]. The ACTN3 R allele was
      associated with high results of performance tests in males only in combination
      with other genes (standing long-jump test: P = 0.021; handgrip strength test: P <
      0.0001). Furthermore, the male carriers of the PPARA gene C allele demonstrated
      the best results of handgrip strength testing than GG homozygotes [GG 14.6 (4.0)
      kg, GC/CC 15.7 (4.3) kg; P = 0.048]. Thus, the ACE, ACTN3 and PPARA gene variants
      are associated with strength-related traits in physically active middle school
      age boys.

PMID- 22983823
TI  - Perceived impact of cancer treatment on diabetes self-management.
AB  - PURPOSE: The purpose of this study was to identify the impact that cancer and its
      treatment had on diabetes self-management and to identify common issues that
      individuals with diabetes encounter while undergoing chemotherapy. METHODS: This
      exploratory study utilized a baseline self-administered written survey and an 8
      week telephone follow-up survey that included 2 open-ended questions. Forty-three
      adults aged 50 or older with diabetes and a solid tumor cancer receiving
      chemotherapy were recruited from 8 community outpatient cancer centers in
      Michigan and Ohio. Descriptives, t tests, and correlations were utilized to
      analyze the data. Content analysis was used to analyze the data from the open
      ended questions. RESULTS: After a minimum of 8 weeks of chemotherapy, patients
      performed significantly fewer diabetes self-management behaviors. The majority of
      individuals experienced a moderate to high impact on their ability to perform
      diabetes self-management activities while receiving chemotherapy. Exercise,
      ability to eat and drink, and monitoring blood sugars were most affected. Three
      themes identifying patient issues were noted: self-management issues, health
      issues, and prioritization. CONCLUSIONS: Cancer treatment and cancer-related
      symptoms can have a negative impact on diabetes self-management behaviors in
      adults with diabetes who are undergoing chemotherapy. Diabetes self-management
      education is targeted to improve health outcomes in patients with diabetes and
      cancer and addresses the "cause" not just the "source" of the problem needs to be
      developed. Further research needs to be done to address issues related to
      glycemic control and health-related outcomes in this population.

PMID- 22983824
TI  - Mammary gland development is delayed in mice deficient for aminopeptidase N.
AB  - Development of the mammary gland requires the coordinated action of proteolytic
      enzymes during two phases of remodelling. Firstly, new ducts and side-branches
      thereof need to be established during pregnancy to generate an extensive ductal
      tree allowing the secretion and transport of milk. A second wave of remodelling
      occurs during mammary involution after weaning. We have analysed the role of the
      cell surface protease aminopeptidase N (Anpep, APN, CD13) during these processes
      using Anpep deficient and Anpep over-expressing mice. We find that APN deficiency
      significantly delays mammary gland morphogenesis during gestation. The defect is
      characterised by a reduction in alveolar buds and duct branching at mid
      pregnancy. Conversely over-expression of Anpep leads to accelerated ductal
      development. This indicates that Anpep plays a critical role in the proteolytic
      remodelling of mammary tissue during adult mammary development.

PMID- 22983825
TI  - Antioxidant properties of diorganoyl diselenides and ditellurides: modulation by
      organic aryl or naphthyl moiety.
AB  - Diorganoyl dichalcogenide compouds can have antioxidant activity in different in
      vitro and in vivo models. Here, we have compared the potential antioxidant
      activity of 1-dinaphthyl diselenide (1-NapSe)(2), 2-dinaphthyl diselenide (2
      NapSe)(2), 1-dinaphthyl distelluride (1-NapTe)(2), 2-dinaphthyl ditelluride (2
      NapTe)(2) with their well-studied analogs diphenyl diselenide ((PhSe)(2)) and
      diphenyl telluride ((PhTe)(2)). (PhSe)(2), (PhTe)(2), and naphthalene analogs
      inhibited Fe(II)-induced lipid peroxidation, catalytically decomposed hydrogen
      peroxide and oxidized thiols, such as dithiothreitol (DTT), Cysteine (CYS),
      dimercaptopropionic acid (DMPS), and thiophenol (PhSH). (PhSe)(2) was the less
      potent of the tested compounds against Fe(II)-induced lipid peroxidation in brain
      homogenates and the change in the organic moiety from an aryl to naphthyl group
      increased considerably the antioxidant potency of diselenide compounds. However,
      the change from aryl to naphthyl had little effect on the thio-peroxidase-like
      activity of diorganoyl dichalcogenides. These results suggest that minor changes
      in the organic moiety of aromatic diselenide compounds can modify profoundly
      their capacity to inhibit iron-induced lipid peroxidation. The pharmacological
      properties of organochalcogens are thought to be linked to their capacity of
      modulating oxidative stress. Consequently, it becomes important to explore the
      toxicological properties of dinaphthyl diselenides and ditellurides.

PMID- 22983826
TI  - Interleukin-22 protects rat PC12 pheochromocytoma cells from serum deprivation
      induced cell death.
AB  - Interleukin-22 (IL-22), an IL-10 family cytokine, mediates the crosstalk between
      leukocytes and epithelial cells. Previous studies reported that IL-22 expresses
      in mouse brain, and the rat PC12 cells are responsive to IL-22 stimulation.
      However, the biological roles of IL-22 in neuronal cells remain largely unknown.
      We show here that IL-22 activates Stat3, p38 mitogen-activated protein kinases
      (MAPK), and Akt pathways and inhibits Erk/MAPK pathway in naive PC12 cells. We
      further demonstrate that IL-22 protects naive PC12 cells from serum starvation
      induced cell death via the Jak1/Stat3 and Akt pathways. We also show that IL-22
      has no effects on naive PC12 cell proliferation and cannot protect naive PC12
      cells from 1-methyl-4-phenylpyridinium (MPP(+))-induced cytotoxicity. However, IL
      22 exerts a dose-dependent protective effect on MPP(+)-induced neurodegeneration
      in nerve growth factor-differentiated PC12 cells. Overall, our data suggest that
      IL-22 might play a role in neurological processes. To our knowledge, this is the
      first report showing that IL-22 confers a neuroprotective function, which may
      provide a new therapeutic option for treatment of neurodegenerative diseases.

PMID- 22983827
TI  - Association between polymorphisms of XRCC1 and ADPRT genes and ovarian cancer
      survival with platinum-based chemotherapy in Chinese population.
AB  - The role of DNA repair gene polymorphisms in cancer development, progression, and
      response to treatment has received increased attention. We conducted a
      prospective study to determine whether associations exist between two
      polymorphisms in XRCC1 and ADPRT and the outcomes of Chinese ovarian cancer
      patients treated with platinum-based chemotherapy. A total of 335 new cases of
      ovarian cancer were consecutively collected between May 2005 and May 2007. Follow
      up lasted for 4 years, and the outcome measure was survival time. Individuals
      carrying XRCC1 194Trp/Trp had a longer survival time than did those with the
      Arg/Arg genotype. Similarly, those carrying XRCC1 399 Gln/Gln genotypes had 0.44
      fold the risk of death than those with the Arg/Arg genotype. The combination of
      XRCC1 194 Trp allele and 399 Gln allele could decrease the death risk of ovarian
      cancer. In summary, this study is the first to evaluate the associations between
      polymorphisms in DNA repair gene polymorphism and the risk of ovarian cancer in
      Chinese population. Our study found a significant association between XRCC1
      Arg399Gln and XRCC1 Arg194Trp polymorphism and the clinical outcome of ovarian
      cancer. Furthermore, studies with larger sample sizes are still needed to confirm
      these associations in Chinese population.

PMID- 22983828
TI  - HuR-hnRNP interactions and the effect of cellular stress.
AB  - The heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute an important
      group of RNA-binding proteins (RBPs) that play an active role in post
      transcriptional gene regulation. Here, we focus on representative members of the
      hnRNP group of RBPs, namely hnRNP A1 and hnRNP C1/C2, which participate mainly in
      RNA splicing, as well as on HuR, a prototype of the AU-rich element-binding
      proteins (ARE-BP), which has an established role in regulating the stability and
      translation of target mRNAs. HuR and most hnRNPs are primarily localized in the
      nucleoplasm, and they can shuttle between the nucleus and the cytoplasm. Herein,
      we have extended our recently reported findings on the ability of HuR to
      associate with the immunopurified from mammalian cell extracts hnRNP and mRNP
      complexes by the application of an anti-HuR antibody that selects HuR-RNP
      complexes. We find that the protein components precipitated by the anti-HuR
      antibody are very similar to the hnRNP-HuR complexes reported previously. The in
      vivo association of HuR and hnRNP proteins is examined in the presence and the
      absence of thermal stress by confocal microscopy of intact cells and by in situ
      nuclear matrix preparation. We find notable heat-induced changes of HuR and of
      hnRNP A1, which exit the nucleus and co-localize to large cytoplasmic foci that
      represent heat-induced stress granules. The functional implications of HuR-hnRNP
      interactions in stressed and unstressed cells are discussed.

PMID- 22983829
TI  - Relationship of urinary isoprostanes to prostate cancer occurrence.
AB  - To estimate the oxidative stress in patients with prostate cancer and in a
      control group, we used the biomarker of lipid peroxidation-isoprostanes (8
      isoPGF(2)) and the level of selected antioxidants (glucose and uric acid [UA]).
      The level of urinary isoprostanes was determined in patients and controls using
      an immunoassay kit according to the manufacturer's instruction. The levels of UA
      and glucose were also determined in serum by the use of UA Assay Kit and Glucose
      Assay Kit. We observed a statistically increased the level of isoprostanes in
      urine of patients with prostate cancer in compared with a control group. The
      concentration of tested antioxidants in blood from patients with prostate cancer
      was also higher than in healthy subjects. Moreover, our experiments indicate that
      the correlation between the increased amount of UA and the lipid peroxidation
      exists in prostate cancer patients (in all tested groups). Prostate cancer risk
      by urinary isoprostanes level was analyzed, and a positive association was found
      (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95
      % confidence interval 1.2-2.4; p for trend = 0.03). We suggest that reactive
      oxygen species induce peroxidation of unsaturated fatty acid in patients with
      prostate cancer, and the level of isoprostanes may be used as a non-invasive
      marker for determination of oxidative stress. We also propose that UA may enhance
      the oxidative stress in patients with prostate cancer.

PMID- 22983830
TI  - Serum vitamin D levels are decreased in patients without remission of Graves'
      disease.

PMID- 22983831
TI  - Ectopic acromegaly due to growth hormone releasing hormone.
AB  - Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing
      hormone (GHRH) is rarely encountered. We review the literature on ectopic
      acromegaly and present the index report of ectopic acromegaly secondary to GHRH
      secretion from a mediastinal paraganglioma. Clinical and pathological
      manifestations and therapeutic management of 99 patients with ectopic acromegaly
      are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by
      a neuroendocrine tumor in the lung and pancreas. We report an additional cause of
      ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of
      ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of
      GHRH secretion and expression. Management of ectopic acromegaly consists of
      surgical resection of the primary tumor and biochemical normalization, with
      possible adjuvant use of somatostatin analogs. The review demonstrates that there
      are several tumor types, including paragangliomas which may secrete GHRH, leading
      to acromegaly. Clinical and laboratory manifestations of the syndrome and
      challenges in diagnosis and management of these rarely encountered patients
      require early diagnosis and appropriate treatment to prevent long-term morbidity
      and mortality with ectopic acromegaly.

PMID- 22983832
TI  - Racial differences in adiponectin and leptin in healthy premenopausal women.
AB  - The aim of this article is to longitudinally investigate racial differences in
      serum adiponectin and leptin in European-American (EA) and African-American (AA)
      women in the overweight and weight-reduced states. Sixty-two EA and 58 AA
      premenopausal women were weight reduced from body mass index (BMI) 27-30 kg/m(2)
      to BMI <= 24. Fasting serum adiponectin and leptin were determined; body
      composition and intra-abdominal adipose tissue (IAAT) were measured with dual
      energy X-ray absorptiometry and computed tomography, respectively. In repeated
      measure MANOVA, there was a significant race effect for IAAT and total fat mass;
      compared to AA women, EA women had higher IAAT and total fat mass (p < 0.0001 and
      p = 0.027, respectively). In the mixed-model for adiponectin that adjusted for
      IAAT, limb fat, and total fat, race was significantly associated with adiponectin
      (p = 0.046). AA women had significantly lower adjusted adiponectin compared to EA
      women at baseline [7.67 (6.85, 8.60) vs. 9.32 (8.34, 10.4) MUg/ml, p < 0.05] and
      following weight loss [9.75 (8.70, 10.9) vs. 11.8 (10.6, 13.2) MUg/ml, p < 0.05].
      In a mixed-model for leptin that adjusted for insulin, estradiol, and fat mass,
      race was significantly associated with leptin (p < 0.0001). AA women had
      significantly higher adjusted leptin compared to EA women at baseline [24.7
      (22.3, 27.4) vs. 19.9 (18.1, 21.8) ng/dl, p < 0.05] and following weight loss
      [11.7 (10.2, 13.3) vs. 8.48 (7.50, 9.57) ng/dl, p < 0.05]. Despite having a more
      favorable body fat distribution, AA women had lower adjusted adiponectin and
      higher leptin. Differences in body composition and fat distribution do not appear
      to be significant factors in explaining lower adiponectin and higher leptin in AA
      women.

PMID- 22983833
TI  - Safety of the paravertebral block in patients ineligible for epidural block
      undergoing pulmonary resection.
AB  - OBJECTIVE: We previously reported the noninferiority of paravertebral block (PVB)
      to epidural block. In this study, we assessed whether PVB via an intrathoracic
      approach was also safe for the patients ineligible for epidural block because of,
      for example, anticoagulation or antiplatelet therapy. METHODS: Patients admitted
      to our hospital for pulmonary resection between April 2010 and March 2012, and
      who were ineligible for epidural block for various reasons, were enrolled in this
      study. A catheter for PVB was inserted in the operative field by the surgeons
      just before closing the chest. Ropivacaine of 0.2 % was injected at 4 ml/h using
      an infuser pump for 5 days. Concurrent use of intravenous patient controlled
      analgesia (IVPCA) for 2 days with PVB was permitted as a post-operative analgesic
      at the discretion of anesthesiologists. We estimated the post-operative
      complications in these patients. RESULTS: A total of 35 (15.8 %) consecutive
      patients were enrolled in this study and successfully completed the study
      protocol. Thirty-two patients received concurrent IVPCA treatment. Post-operative
      complications due to PVB were not observed, but other complications included 1
      incidence of atrial fibrillation, 1 hypertension, 1 pleural fluid accumulation, 1
      respiratory failure requiring mechanical ventilation, and 1 of late chest pain
      requiring intercostal nerve block. CONCLUSION: This study suggests that PVB is
      safe in patients ineligible for epidural block and can contribute to their pain
      relief following pulmonary resection procedure including video-assisted thoracic
      surgery.

PMID- 22983834
TI  - The Gastro-Laryngeal Tube for interventional endoscopic biliopancreatic
      procedures in anesthetized patients.
AB  - The Gastro-Laryngeal Tube (G-LT) is a modification of the laryngeal tube which
      provides a dedicated channel for the insertion of an endoscope while acting as a
      supraglottic airway for ventilation. The aim of this study was to assess the
      safety and effectiveness of this device in patients undergoing anesthesia for
      interventional endoscopic biliopancreatic procedures (IEBPPs).A total of 22
      patients were included in the study. The G-LT was inserted successfully in all
      patients. Arterial oxygen saturation was stable; the mean value was 97.9%. The
      IEBPPs were performed successfully in all patients through the endoscopic
      channel, with a mean duration of 99 minutes. The maneuverability of the endoscope
      was considered good in all patients. There were two cases of sore throat after
      the procedures, two cases of asymptomatic erosion of the upper esophageal mucosa,
      one case of Mallory-Weiss syndrome, and one case of pancreatitis after endoscopic
      retrograde cholangiopancreatography.Our results suggest that the G-LT is an
      effective and secure device for airway management and for use during IEBPPs.

PMID- 22983835
TI  - The association between polymorphisms in the leptin receptor gene and risk of
      breast cancer: a systematic review and pooled analysis.
AB  - Many epidemiological studies have found that leptin correlates to body fat extent
      and breast cancer. Leptin exerts its physiological action through the leptin
      receptor (LEPR). However, published data on the association between LEPR alleles
      and breast cancer occurrence have led to in contradictory results. A total of 10
      studies were identified to the meta-analysis, including 4,644 cases and 5,485
      controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464
      controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and
      rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence
      intervals (CI) for breast cancer risk associated with LEPR genotypes were
      estimated. Elevated breast cancer risk was associated with LEPR rs1137101
      polymorphism when all studies were pooled in the meta-analysis (allele contrast
      model: OR = 0.71, 95 % CI = 0.551-0.997). In the stratified analysis by
      ethnicity, significantly increased risks were also found among Asians for allele
      contrast model (OR 0.414, 95 % CI 0.312-0.550) and dominant model (OR 0.537, 95 %
      CI 0.370-0.781); for Africans, significantly increased risks were also found for
      allele contrast model (OR 0.716, 95 % CI 0.595-0.861), homozygote codominant (OR
      0.537, 95 % CI 0.370-0.781) and dominant model (OR 1.595, 95 % CI 1.207-2.108).
      And significantly elevated breast cancer risk was associated with LEPR rs1137100
      polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603-0.720) and
      homozygote codominant models (OR = 0.344, 95 % CI = 0.282-0.421). For LEPR
      rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations
      were detected in all comparison models.  This pooled analysis suggested that
      rs1137101 and rs1137100 polymorphisms were significantly correlated with breast
      cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR
      rs1137100 variant were low-penetrant risk factors for developing breast cancer.
      Further, no significant associations existed between LEPR rs8179183, rs4655537,
      and rs3762274 polymorphisms and risk of breast cancer.

PMID- 22983836
TI  - Recombinant viral protein VP1 suppresses HER-2 expression and
      migration/metastasis of breast cancer.
AB  - Breast cancer is one of the most common cancers in women worldwide and metastasis
      is the major cause of breast cancer death. Development of new therapeutic agents
      for inhibiting breast cancer metastasis is therefore an urgent need. We
      previously demonstrated that recombinant DNA-derived viral capsid protein VP1
      (rVP1) of foot-and-mouth disease virus-induced apoptosis of MCF-7 breast cancer
      cells in vitro. Here, we investigated whether rVP1 exhibits any inhibitory
      effects on migration/metastasis and human epidermal growth factor receptor 2 (HER
      2), a well-known biomarker for poor prognosis of breast cancer. The effects of
      rVP1 on cancer cell migration/invasion and metastasis were evaluated using
      Transwell migration assay and animal cancer models of metastasis. Western
      blotting, RT-PCR, flow cytometry, immunohistochemistry, and immunofluorescence
      staining techniques were used to investigate the effects of rVP1 on HER-2 and
      signal transduction mediators. Non-cytotoxic concentrations of rVP1-induced
      mesenchymal-epithelial transition and significantly suppressed AP-2alpha and HER
      2 expression as well as the migration and invasion of a variety of breast cancer
      cell lines in a beta1-integrin-dependent manner in vitro. Gross and
      histopathologic examinations showed that rVP1 also suppressed metastasis of
      several breast cancer cell lines, including HER-2-overexpressing SK-BR-3 and BT
      474 cells to lung, liver, or peripheral lymph node in orthotopic
      allograft/xenograft murine models. In addition, rVP1 significantly prolonged
      survival in breast cancer-bearing mice. Notably, no apparent side effects of rVP1
      were detected, as shown by normal complete blood count levels and serum
      biochemistry profiles, including AST, ALT, BUN, and creatine. This study
      demonstrates that rVP1 suppresses the migration, invasion, and metastasis of
      breast cancer cells via binding to beta1 integrin receptor and down-regulation of
      AP-2alpha and HER-2 expression. The effectiveness of rVP1 on inhibiting
      migration/metastasis of breast cancer and HER-2 expression suggests that it may
      be suitable for serving as potential therapeutics for metastatic breast cancer
      particularly HER-2-overexpressing cancer.

PMID- 22983837
TI  - Cost effectiveness of new breast cancer radiotherapy technologies in diverse
      populations.
AB  - Accelerated partial breast radiotherapy (RT) strategies (3-D conformal external
      beam RT (3-D CRT) and brachytherapy with balloon catheter) reduce time and
      transportation burdens of whole breast RT for breast cancer. Long-term clinical
      trial evidence is unavailable for accelerated modalities, but uncertainty might
      be acceptable for patients likely to receive suboptimal whole breast RT. The
      objective of this study is to assess the cost effectiveness of accelerated
      partial breast RT compared to on-time and delayed whole breast RT. The design
      used in this study is decision analytic Markov model. The data sources are
      published literature; and national/federal sources. The target population of this
      study is a hypothetical cohort of 60 years old women previously treated with
      breast-conserving surgery for node-negative, estrogen receptor-positive breast
      cancer with tumors <1 cm. The time horizon is 15 years, and the perspective is
      societal. The interventions are whole breast RT, 3-D CRT, and brachytherapy
      breast irradiation. The outcome measures are costs (2008 US$), quality-adjusted
      life years (QALYs), and incremental cost-effectiveness ratios. The base-case
      results were: 3-D CRT was the preferred strategy, costing on average $10,800 and
      yielding 11.21 QALYs. On-time whole breast RT costs $368,000/QALY compared to 3-D
      CRT, above the $100,000/QALY WTP threshold. 3-D CRT was also preferred over
      delayed whole breast RT. Brachytherapy was never preferred. Sensitivity  analysis
      indicated that the results were sensitive to the rate of recurrence outside the
      initial tumor quadrant ("elsewhere failure") in one-way analysis. Probabilistic
      sensitivity analysis indicated that results were sensitive to parameter
      uncertainty, and that the elsewhere-failure rate and treatment preferences may
      drive results. The limitation of this study is that efficacy estimates are
      derived from studies that may not fully represent the population modeled. As a
      conclusion, 3-D CRT was preferred to whole breast RT and for women likely to
      delay RT, indicating that 3-D CRT could be targeted more efficiently before
      randomized trial evidence.

PMID- 22983838
TI  - Gastric volvulus in children: our experience.
AB  - Gastric volvulus is an extremely rare disorder in the pediatric age group. It is
      a complex entity as to the etiology and management. The study was conducted to
      evaluate etiology, mode of presentation, management, and outcome in our patients
      with gastric volvulus. It was a retrospective study of 10 patients with gastric
      volvulus managed during May 2006 and October 2010. The medical record of these
      patients including history, clinical examination, investigations, operative
      notes, and the outcome was reviewed. Of the ten patients, seven were males and
      three females. The mean age of presentation was 2.87 years. Half (50 %) of the
      patients showed typical Borchardt triad whereas in other patients the
      presentation was variable. In eight patients, the diagnosis was precisely made
      with the help of radiological investigations. At operation, three patients had
      primary gastric volvulus, and seven had secondary gastric volvulus. The
      predisposing factors leading to secondary gastric volvulus were eventration of
      diaphragm, hiatus hernia, congenital diaphragmatic hernia, malrotation, and
      traumatic diaphragmatic rupture. Seven patients had organoaxial volvulus and
      three showed mesenterioaxial. Gastropexy was performed in three patients (primary
      gastric volvulus). In seven patients (secondary gastric volvulus), the
      predisposing anatomical defects were corrected without adding gastropexy in the
      regime. One patient with traumatic rupture of the diaphragm died. There was no
      recurrence in any patient over a mean follow up of 3.7 years (SD +/- 1.27).
      Secondary gastric volvulus is prevalent with diaphragmatic defects sharing major
      contribution in the etiology. Classical Borchardt triad is seen in 50 % cases of
      pediatric gastric volvulus. Correction of predisposing factors alone is
      sufficient to manage secondary gastric volvulus in children.

PMID- 22983839
TI  - Narrow band imaging versus white light gastroscopy in detecting potentially
      premalignant gastric lesions: a randomized prospective crossover study.
AB  - BACKGROUND AND AIMS: Narrow band imaging (NBI) detects mucosal surface details
      (pit pattern) as well as the microvasculature pattern of mucosa. In premalignant
      conditions the pattern and regularity of pits and microvasculature are altered.
      We aimed to assess whether NBI is superior to conventional white light
      gastroscopy (WLG) in detecting potentially premalignant gastric lesions. PATIENTS
      AND METHODS: We conducted a randomized prospective crossover study from January
      2009 to July 2009. Patients above 45 years of age with dyspepsia in absence of
      alarm symptoms underwent gastric mucosal examination using WLG and NBI in the
      same session by different endoscopists who were blinded to each other's endoscopy
      findings. Biopsy was taken if required at the end of the second gastroscopy after
      a third observer reviewed reports of both scopists. The yield of gastric
      potentially premalignant lesions (atrophic gastritis, intestinal metaplasia,
      dysplasia, adenomatous polyp) was compared for both procedures. RESULTS: Two
      hundred [mean age 52.3 (6.4) years, males-66 %] patients participated in the
      study. Thirty-two patients were diagnosed to have potentially premalignant
      lesions using both modalities. No patient had early gastric cancer. WLG detected
      lesions in 17 patients (atrophic gastritis in 12, atrophic gastritis with
      intestinal metaplasia in 5) and NBI in 31 patients (atrophic gastritis in 22,
      atrophic gastritis with intestinal metaplasia in 9). The sensitivity of lesion
      detection by NBI was significantly higher than WLG (p = 0.001). CONCLUSIONS: NBI
      was superior to WLG for detection of atrophic gastritis and intestinal
      metaplasia.

PMID- 22983840
TI  - Esophageal adenocarcinoma versus squamous cell carcinoma: retrospective hospital
      based analysis of a 12-year temporal trend.
AB  - There is a paucity of literature from the Indian subcontinent looking at the
      prevalence of esophageal cancer by histological type. In our study, we
      ascertained the relative proportion and location of adenocarcinoma (AC) and
      squamous cell carcinoma (SCC) of the esophagus at a referral hospital in Mumbai,
      India over a 12-year period to assess whether a time-trend existed. A
      retrospective analysis was carried out on patients who were diagnosed with and/or
      treated for esophageal cancer at the P D Hinduja Hospital and Research Centre in
      Mumbai between January 1, 2000 and December 31, 2011. Data were procured from
      histopathology and oncology registers of the institute, the database of the
      Gastroenterology consultants, the Endoscopy Department records and from the
      Medical Records Department. Of the 445 cases of esophageal cancer with known
      histology, 104 (23 %) were AC and 314 (71 %) were SCC. Over the 12-year period,
      the proportions of AC compared to SCC did not show a statistically significant
      temporal change (p = 0.145). AC comprised nearly a quarter of esophageal
      carcinoma in Mumbai. There has been no significant change in the number and
      proportion of AC and SCC in the 12-year period.

PMID- 22983841
TI  - Acute and chronic inflammation studies of Strobilanthes callosus leaves extract
      on rat model.
AB  - AIM: To assess the protective efficacy of Strobilanthes callosus against the
      acute and chronic inflammation on rat model. METHODS: Inflammation was induced by
      carrageen and Freund's complete adjuvant in plantar surface of the rats. The
      ethanol, chloroform and petroleum ether extracts in three divided doses (100, 200
      and 400 mg/kg) were administered orally. Diclofenac sodium (10 mg/kg),
      prednisolone (5 mg/kg) and methotrexate (0.5 mg/kg) were used as standard. The
      statistical significance between means was analyzed using a one-way analysis of
      variance followed by Tukey's multiple comparison test. A p <0.005 was considered
      as statistically significant. RESULTS: Pet. ether (200 and 400 mg/kg) and ethanol
      extract (100 and 400 mg/kg) showed statistically significant (p < 0.001) effect
      in analgesic activity. In a carrageen-induced model, only pet. ether extract (100
      and 400 mg/kg) confirmed statistically significant effect (p < 0.001) at every
      interval (four in all) of 1 h. In Freund's adjuvant model, Pet ether and ethanol
      extract (200 and 400 mg/kg) have shown statistically significant effect (p <
      0.001) and in case of chloroform extract only single dose (400 mg/kg) were
      observed statistically significant results considered to be anti-arthritic
      effects. The histopathology pictures showed there was positive inhibition of
      arthritis at a certain level in different groups compared to positive control
      group. CONCLUSION: Pet. ether and ethanol extracts of S. callosus were observed
      to have a promising efficacy against acute and chronic inflammation.

PMID- 22983842
TI  - Dual promoter expression system with insulator ensures a stringent tissue
      specific regulation of two reporter genes in the transgenic fish.
AB  - The precise control of spatiotemporal expression of target genes is crucial when
      establishing transgenic animals, and the introduction of genes for fluorescent
      marker proteins is inevitable for accelerating research at molecular levels. To
      assist this, we constructed a novel dual promoter expression vector for two
      independent reporter genes, green fluorescent protein (GFP) and red fluorescent
      protein (mCherry). Their expression is designed under the control of two distinct
      tissue-specific promoters, e.g. zebrafish cardiac muscle-specific promoter
      (cmlc2) and medaka skeletal muscle-specific promoter (myl2) derived from the
      myosin light chain 2 genes, and they are placed in a head-to-head orientation.
      After microinjecting the dual promoter expression vector into fertilized eggs of
      medaka, the developing fish embryos and the resulting transgenic fish lines
      showed strong GFP signal in the whole body (skeletal muscle) and mCherry signal
      in the heart (cardiac muscle). However, weak GFP signal was observed in the
      heart, indicating a leakiness of the skeletal muscle promoter. To improve the
      stringency of dual promoter expression, we inserted two chicken-derived
      insulators, e.g. tandem copies of the core sequence (250 bp) of cHS4 (5'
      hypersensitive site-4 chicken beta-globin insulator), in the boundary of two
      promoters. The dual promoter expression vector with insulator now ensured the
      stringent tissue-specific expression in the transgenic fish lines. Thus, our dual
      promoter expression system with insulator is compatible to the conventional IRES
      and fused reporter gene systems and will be an alternative method to produce the
      transgenic fishes.

PMID- 22983843
TI  - Chemopreventive properties of dietary rice bran: current status and future
      prospects.
AB  - Emerging evidence suggests that dietary rice bran may exert beneficial effects
      against several types of cancer, such as breast, lung, liver, and colorectal
      cancer. The chemopreventive potential has been related to the bioactive
      phytochemicals present in the bran portion of the rice such as ferulic acid,
      tricin, beta-sitosterol, gamma-oryzanol, tocotrienols/tocopherols, and phytic
      acid. Studies have shown that the anticancer effects of the rice bran-derived
      bioactive components are mediated through their ability to induce apoptosis,
      inhibit cell proliferation, and alter cell cycle progression in malignant cells.
      Rice bran bioactive components protect against tissue damage through the
      scavenging of free radicals and the blocking of chronic inflammatory responses.
      Rice bran phytochemicals have also been shown to activate anticancer immune
      responses as well as affecting the colonic tumor microenvironment in favor of
      enhanced colorectal cancer chemoprevention. This is accomplished through the
      modulation of gut microflora communities and the regulation of carcinogen
      metabolizing enzymes. In addition, the low cost of rice production and the
      accessibility of rice bran make it an appealing candidate for global dietary
      chemoprevention. Therefore, the establishment of dietary rice bran as a practical
      food-derived chemopreventive agent has the potential to have a significant impact
      on cancer prevention for the global population.

PMID- 22983844
TI  - Online tools for bioinformatics analyses in nutrition sciences.
AB  - Recent advances in "omics" research have resulted in the creation of large
      datasets that were generated by consortiums and centers, small datasets that were
      generated by individual investigators, and bioinformatics tools for mining these
      datasets. It is important for nutrition laboratories to take full advantage of
      the analysis tools to interrogate datasets for information relevant to genomics,
      epigenomics, transcriptomics, proteomics, and metabolomics. This review provides
      guidance regarding bioinformatics resources that are currently available in the
      public domain, with the intent to provide a starting point for investigators who
      want to take advantage of the opportunities provided by the bioinformatics field.

PMID- 22983845
TI  - Copper imbalances in ruminants and humans: unexpected common ground.
AB  - Ruminants are more vulnerable to copper deficiency than humans because rumen
      sulfide generation lowers copper availability from forage, increasing the risk of
      conditions such as swayback in lambs. Molybdenum-rich pastures promote
      thiomolybdate (TM) synthesis and formation of unabsorbable Cu-TM complexes,
      turning risk to clinical reality (hypocuprosis). Selection pressures created
      ruminant species with tolerance of deficiency but vulnerability to copper
      toxicity in alien environments, such as specific pathogen-free units. By
      contrast, cases of copper imbalance in humans seemed confined to rare genetic
      aberrations of copper metabolism. Recent descriptions of human swayback and the
      exploratory use of TM for the treatment of Wilson's disease, tumor growth,
      inflammatory diseases, and Alzheimer's disease have created unexpected common
      ground. The incidence of pre-hemolytic copper poisoning in specific pathogen-free
      lambs was reduced by an infection with Mycobacterium avium that left them more
      responsive to treatment with TM but vulnerable to long-term copper depletion.
      Copper requirements in ruminants and humans may need an extra allowance for the
      "copper cost" of immunity to infection. Residual cuproenzyme inhibition in TM
      treated lambs and anomalies in plasma copper composition that appeared to depend
      on liver copper status raise this question "can chelating capacity be harnessed
      without inducing copper-deficiency in ruminants or humans?" A model of equilibria
      between exogenous (TM) and endogenous chelators (e.g., albumin, metallothionein)
      is used to predict risk of exposure and hypocuprosis; although risk of natural
      exposure in humans is remote, vulnerability to TM-induced copper deficiency may
      be high. Biomarkers of TM impact are needed, and copper chaperones for inhibited
      cuproenzymes are prime candidates.

PMID- 22983846
TI  - Biological determinants linking infant weight gain and child obesity: current
      knowledge and future directions.
AB  - Childhood obesity rates have reached epidemic proportions. Excessive weight gain
      in infancy is associated with persistence of elevated weight status and later
      obesity. In this review, we make the case that weight gain in the first 6 mo is
      especially predictive of later obesity risk due to the metabolic programming that
      can occur early postpartum. The current state of knowledge regarding the
      biological determinants of excess infant weight gain is reviewed, with particular
      focus on infant feeding choice. Potential mechanisms by which different feeding
      approaches may program the metabolic profile of the infant, causing the link
      between early weight gain and later obesity are proposed. These mechanisms are
      likely highly complex and involve synergistic interactions between endocrine
      effects and factors that alter the inflammatory and oxidative stress status of
      the infant. Gaps in current knowledge are highlighted. These include a lack of
      data describing 1) what type of infant body fat distribution may impart risk and
      2) how maternal metabolic dysfunction (obesity and/or diabetes) may affect milk
      composition and exert downstream effects on infant metabolism. Improved
      understanding and management of these early postnatal determinants of childhood
      obesity may have great impact on reducing its prevalence.

PMID- 22983847
TI  - Nutritional factors influencing intestinal health of the neonate.
AB  - Dietary nutrients are essential for gastrointestinal (GI) growth and function,
      and nutritional support of GI growth and development is a significant component
      of infant care. For healthy full-term neonates, nutritional provisions of the
      mother's milk and/or formula will support normal maturation of structure and
      function of the GI tract in most infants. The composition of breast milk affects
      GI barrier function and development of a competent mucosal immune system. The
      functional nutrients and other bioactive components of milk support a
      microenvironment for gut protection and maturation. However, premature infants
      struggle with feeding tolerance impairing normal GI function, leading to
      intestinal dysfunction and even death. The high prevalence worldwide of enteric
      diseases and dysfunction in neonates has led to much interest in understanding
      the role of nutrients and food components in the establishment and maintenance of
      a functioning GI tract. Neonates who do not receive enteral feeding as either
      mother's milk or formula are supported by total parental nutrition (TPN). The
      lack of enteral nutrition can compound intestinal dysfunction, leading to high
      morbidity and mortality in intestinally compromised infants. Reciprocally,
      enteral stimulation of an immature GI tract can also compound intestinal
      dysfunction. Therefore, further understanding of nutrient interactions with the
      mucosa is necessary to define nutritional requirements of the developing GI tract
      to minimize intestinal complications and infant morbidity. Piglet models of
      intestinal development and function are similar to humans, and this review
      summarizes recent findings regarding nutrient requirements for growth and
      maintenance of intestinal health. In particular, this article reviews the role of
      specific amino acids (arginine, glutamine, glutamate, and threonine), fatty acids
      (long chain polyunsaturated, medium chain, and short chain), various prebiotic
      carbohydrates (short-chain fructo-oligosaccharide, fructo--oligosaccharide, lacto
      N-neotetraose, human milk oligosaccharide, polydextrose, and galacto
      oligosaccharide), and probiotics that have been examined in the suckling piglet
      model of intestinal health.

PMID- 22983849
TI  - Institute of Medicine. 2012. Accelerating progress in obesity prevention: solving
      the weight of the nation. Washington, DC: the National Academies Press.

PMID- 22983848
TI  - The role of whole grains in body weight regulation.
AB  - Whole grain (WG)-rich diets are purported to have a variety of health benefits,
      including a favorable role in body weight regulation. Current dietary
      recommendations advocate substituting WG for refined grains (RG), because many of
      the beneficial bioactive components intrinsic to WG are lost during the refining
      process. Epidemiological studies consistently demonstrate that higher intakes of
      WG, but not RG, are associated with lower BMI and/or reduced risk of obesity.
      However, recent clinical trials have failed to support a role for WG in promoting
      weight loss or maintenance. Though the biochemical and structural characteristics
      of WG have been shown to modulate appetite, nutrient availability, and energy
      utilization, the capacity of WG foods to elicit these effects varies with the
      type and amount of grain consumed as well as the nature of its consumption. As
      such, WG foods differentially affect physiologic factors influencing body weight
      with the common practice of processing and reconstituting WG ingredients during
      food production likely mitigating the capacity for WG to benefit body weight
      regulation.

PMID- 22983851
TI  - Zinc nutrition from discovery to global health impact.

PMID- 22983850
TI  - Exploring the factors that affect blood cholesterol and heart disease risk: is
      dietary cholesterol as bad for you as history leads us to believe?
AB  - This paper summarizes presentations given at the 2011 Experimental Biology
      meetings about the latest research and a paleoanthropological perspective
      pertaining to the relationship between dietary cholesterol intake and
      cardiovascular disease risk. For much of the past 50 years, a great deal of the
      scientific literature regarding dietary fat and cholesterol intake has indicated
      a strong positive correlation with heart disease. In recent years, however, there
      have been a number of epidemiological studies that did not support a relationship
      between cholesterol intake and cardiovascular disease. Further, a number of
      recent clinical trials that looked at the effects of long-term egg consumption
      (as a vehicle for dietary cholesterol) reported no negative impact on various
      indices of cardiovascular health and disease. Coupled with data indicating that
      the impact of lowering dietary cholesterol intake on serum LDL levels is small
      compared with other dietary and lifestyle factors, there is a need to consider
      how otherwise healthy foods can be incorporated in the diet to meet current
      dietary cholesterol recommendations. Because eggs are a healthful food, it is
      particularly important that sensible strategies be recommended for inclusions of
      eggs in a healthy diet.

PMID- 22983852
TI  - Probiotics for optimal nutrition: from efficacy to guidelines.

PMID- 22983853
TI  - Establishing and evaluating health claims for probiotics.

PMID- 22983854
TI  - Frontiers in fiber nutrition: research and applications.

PMID- 22983855
TI  - Expanding the frontiers of nutrition research: new questions, new methods, and
      new approaches.

PMID- 22983856
TI  - Can weight management programs in worksites reduce the obesity epidemic?

PMID- 22983858
TI  - Adipose dysfunction, interaction of reactive oxygen species, and inflammation.

PMID- 22983857
TI  - Nutritional prevention of cognitive decline.

PMID- 22983859
TI  - The role of dietary components in leptin resistance.

PMID- 22983860
TI  - Fructose, sucrose, and high fructose corn syrup: modern scientific findings and
      health implications.

PMID- 22983861
TI  - Real-world nutritional translation blended with food science.

PMID- 22983862
TI  - Food insecurity and health across the lifespan.
AB  - Our symposium entitled, "Food Insecurity and Health across the Lifespan" explored
      the latest research from the economic, medical, pediatric, geriatric, and
      nutrition literature concerning the measurement, prevalence, predictors, and
      consequences of food insecurity across the lifespan, with a focus on chronic
      disease, chronic disease management, and healthcare costs. Consideration of the
      health impacts of food insecurity is a new and timely area of research, with a
      considerable potential for translation of the findings into public policy
      surrounding alleviation of food insecurity. Although it is widely acknowledged
      that food insecurity and hunger are morally unacceptable, strategies to develop
      national policies to alleviate hunger must also approach this problem by
      considering the economic impact of food insecurity on health and well-being. The
      goals of this symposium were to: 1) learn about the prevalence and severity of
      food insecurity in the US across the lifespan and how this is increasing with the
      continued economic downturn; 2) understand the growing body of research that
      documents the impact of varying degrees of food insecurity on physical and mental
      health across the lifespan; 3) examine how food insecurity is related to chronic
      disease; and 4) explore research methodology to determine the impact of food
      insecurity on healthcare costs and utilization. Our symposium provided new and
      novel understandings and research initiatives directed toward alleviating food
      insecurity in America.

PMID- 22983863
TI  - Adopting healthy and sustainable food service guidelines: emerging evidence from
      implementation at the United States Federal Government, New York City, Los
      Angeles County, and Kaiser Permanente.

PMID- 22983864
TI  - Nutritional regulation of epigenetic changes.

PMID- 22983865
TI  - Controversies regarding reported trends: has the obesity epidemic leveled off in
      the United States?

PMID- 22983867
TI  - Swim training of monosodium L-glutamate-obese mice improves the impaired insulin
      receptor tyrosine phosphorylation in pancreatic islets.
AB  - The goal of the present study was to investigate changes on glucose homoeostasis
      and of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1)
      signalling in pancreatic islets from MSG-obese mice submitted to or not submitted
      to swim training. Swim training of 90-day-old MSG mice was used to evaluate
      whether signalling pathways of the IR and IRS-1 in islets are involved with the
      insulin resistance and glucose intolerance observed in this obese animal model.
      The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in
      MSG-obese mice (MSG, 6.7 +/- 0.2 arbitrary units (a.u.); control, 11.5 +/- 0.4
      a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice
      without affecting control mice (MSG, 11.8 +/- 0.3; control, 12.8 +/- 0.2 a.u.).
      Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (pIRS-1)
      by 96 % (MSG, 17.02 +/- 0.6; control, 8.7 +/- 0.2 a.u.), exercise training also
      increased it in both groups (control, 13.6 +/- 0.1; MSG, 22.2 +/- 1.1 a.u.).
      Current research shows that the practice of swim training increases the tyrosine
      phosphorylation of IRS-1 which can modulate the effect caused by obesity in
      insulin receptors.

PMID- 22983868
TI  - Utility of bronchoalveolar lavage in the diagnosis of pulmonary infection in
      children with haematological malignancies.
AB  - BACKGROUND: Fibre-optic bronchoscopy with bronchoalveolar lavage (BAL) is a safe
      procedure and is associated with low morbidity and mortality in immunocompromised
      children. Although many studies have highlighted the advantages of positive BAL
      results in the diagnosis of pulmonary infections, there have been few reports
      examining the impact of a negative BAL result on clinical management in
      immunocompromised children on empiric broad-spectrum antimicrobial therapy. AIM:
      The aim of this study was to evaluate BAL in the diagnosis of pulmonary
      infections in children with haematological malignancies who develop pneumonia
      unresponsive to empiric antimicrobial therapy, and also to determine whether a
      negative BAL result contributed to the clinical management of these patients.
      MATERIALS AND METHODS: A retrospective review of 44 BAL procedures performed in
      33 children with haematological malignancy diagnosed and treated at Our Lady's
      Children Hospital, Crumlin, Dublin 12, Ireland, over a 10-year period was carried
      out. RESULTS: We identified a pathogen causing pneumonia in 24 of 44 BAL
      procedures (54.5 %). The BAL procedure resulted in modification of antimicrobial
      treatment after 20 of 24 procedures with positive results (83.3 %) in 16 of 20
      patients (80 %). Management was changed after 8 of 20 procedures with negative
      results (40 %) in 8 of 18 patients (44.4 %). The procedure was well tolerated in
      all patients. CONCLUSIONS: Our study supports the use of bronchoscopy with BAL as
      a diagnostic intervention in this patient population. We consider BAL a safe
      procedure from which both positive and negative results contribute to the
      patient's clinical management.

PMID- 22983869
TI  - Emmanuel Levinas and the face of Terri Schiavo: bioethical and phenomenological
      reflections on a private tragedy and public spectacle.
AB  - The controversial case of Terri Schiavo came to a close on March 31, 2005, with
      her death following the removal of a percutaneous endoscopic gastrostomy tube.
      This event followed years of controversy and social upheaval. Voices from across
      the entire political and cultural spectrums filled the airwaves and op-ed pages
      of major newspapers. Protests ensued outside of Ms. Schiavo's care facility. Ms.
      Schiavo's parents published videos of their daughter on the internet in an effort
      to prove that she was not in a vegetative state and could potentially recover.
      There is a certain mystery to the entire controversy given the fact that,
      legally, it was largely a matter of settled law. Precedent cases and legal
      statutes clearly set out the proper procedures and decisions to be followed in
      this case. Nonetheless, powerful challenges and virulent opposition to these
      standards arose. Through an investigation of this case as well as a comparative
      study of the case of Dax Cowart (in particular, the documentary depictions of Dax
      Cowart's case) and of a photograph by Joel-Peter Witkin, I plan to investigate
      the source of these social upheavals and hypothesize that they were largely the
      result of a phenomenological reaction to the human face.

PMID- 22983866
TI  - Methylglyoxal, obesity, and diabetes.
AB  - Methylglyoxal (MG) is a highly reactive compound derived mainly from glucose and
      fructose metabolism. This metabolite has been implicated in diabetic
      complications as it is a strong AGE precursor. Furthermore, recent studies
      suggested a role for MG in insulin resistance and beta-cell dysfunction. Although
      several drugs have been developed in the recent years to scavenge MG and inhibit
      AGE formation, we are still far from having an effective strategy to prevent MG
      induced mechanisms. This review summarizes the mechanisms of MG formation,
      detoxification, and action. Furthermore, we review the current knowledge about
      its implication on the pathophysiology and complications of obesity and diabetes.

PMID- 22983870
TI  - Close association between genotypes of the Val158Met polymorphism and pain
      perception in pain patients besides breast cancer patients.

PMID- 22983871
TI  - Bilateral simultaneous central serous chorioretinopathy in a teenage girl with
      systemic arterial hypertension.
AB  - We present a case of bilateral simultaneous central serous chorioretinopathy
      (CSCR) in a teenage girl with a history of systemic arterial hypertension. A 19
      year-old Caucasian female, with a history of systemic arterial hypertension,
      presented with gradual decrease in her central vision for 1 month. She was
      diagnosed with bilateral simultaneous CSCR, based on the findings of spectral
      domain optical coherence tomography (SD-OCT), indocyanine green angiography
      (ICG), fundus auto-fluorescence, fluorescein angiography and color fundus
      photographs, which are described. Blood pressure was 134/95 mmHg at presentation.
      Systemic evaluation failed to reveal a cause for the high blood pressure, and
      included a panel of blood tests, which were all normal. Her best-corrected visual
      acuity was 20/30 OD and 20/25 OS. Dilated fundus examination showed normal optic
      discs and retinal vasculature, with no evidence of hypertensive retinopathy.
      However, shallow retinal fluid associated with pigmentary changes was noted in
      the center of both maculae. OCT and ICG findings were consistent with the
      diagnosis of bilateral CSCR. CSCR can manifest in patients with demographics
      outside the range of those previously reported. This is the first report of CSCR
      occurring in a teenage girl, with a history of systemic arterial hypertension. It
      is important to consider this disease in any patient who has a clinically
      compatible presentation.

PMID- 22983872
TI  - Successful conservative management of coronary artery rupture: role of post
      pericardiotomy adhesions as a protective barrier.
AB  - Coronary artery rupture is a rare but potentially life-threatening complication
      of percutaneous coronary interventions (PCI). Grade III perforation and coronary
      artery rupture invariably results in pericardial effusion and tamponade requiring
      urgent pericardiocentesis. We report an elderly male with post coronary artery
      bypass status, who developed right coronary artery rupture during PCI with
      massive extravasation, however post pericardiotomy adhesions resulted in
      contained collection, thus preventing tamponade and need for pericardiocentesis.
      The coronary artery rupture was successfully manages with prolonged balloon
      dilatation followed by stenting.

PMID- 22983873
TI  - Factors associated with mortality and length of stay in hospitalised neonates in
      Eritrea, Africa: a cross-sectional study.
AB  - OBJECTIVE: To determine the factors associated with mortality in a hospitalised
      cohort of infants in Asmara, Eritrea. DESIGN: Retrospective cross-sectional
      review of all 2006 admissions to a specialised neonatal intensive care unit. Data
      on gestational age (prematurity), age at presentation, birth weight, gender, mode
      of delivery, Apgar score, maternal age, birth location, admission diagnosis,
      admission comorbidities, time of admission and outcome were collected. SETTING:
      Orotta Pediatric Hospital 'Specialised Neonatal Intensive Care Unit' (SNCU) in
      Orotta National Maternity Referral Hospital, the nation's only tertiary newborn
      centre. PRIMARY AND SECONDARY OUTCOME MEASURES: Factors associated with mortality
      and length of stay via multivariate regression analysis and the combined
      association of both hypothermia and pneumonia. Other outcome measures were
      determination of the association of admission hypothermia, time of admission and
      pneumonia on mortality. RESULTS: A total of 1502 infants were admitted to the
      SNCU with an average preterm gestational age of 35.9 weeks. 87 died (mortality
      8.2%). In bivariate analysis, the highest mortality rate (10.3%) was seen in
      patient's admitted <1 h after birth. Patients with hypothermia or pneumonia
      exhibited higher mortality rates (13.6% and 13.4%, respectively). In multivariate
      analysis, birth weight <2 kg (p<0.01), birth weight between 2.1 and 2.5 kg
      (p<0.01), Apgar score at 1 min (p<0.01), small for gestational age (p<0.01),
      hypothermia (p<0.04) and pneumonia (p<0.01) were associated with mortality.
      CONCLUSION: Hypothermia, pneumonia, younger gestational age, 1 min Apgar score
      and small size for gestational age are significantly associated with mortality
      and longer length of stay in the Eritrean SNCU.

PMID- 22983874
TI  - Mother's country of birth and prescription of psychotropic medication in Swedish
      adolescents: a life course approach.
AB  - OBJECTIVES: Besides medical needs, psychotropic medication use in adolescence
      might be conditioned by the cultural context of the family. This knowledge is
      relevant for both detecting inequities in healthcare, and identifying information
      bias in epidemiological studies using psychotropic medication as a proxy for
      impaired psychological health. Therefore, we investigated whether, independent of
      needs, the socioeconomic characteristics of the mother's country of birth are
      associated with psychotropic medication use in Swedish-born adolescents. DESIGN:
      Prospective cohort study. SETTING: The Swedish population. PARTICIPANTS: By
      linking the Swedish Medical Birth Registry to other national registers, we
      identified all 324 510 singletons born between 1988 and 1990 and who were alive
      and residing in Sweden until the age of 18 years (2006-2008). PRIMARY AND
      SECONDARY OUTCOME MEASURES: The primary outcome was participants' use of
      psychotropic medication in the year they turned 18. In the analyses, applying a
      life-course approach, we included both the mother's and the children's
      characteristics throughout pregnancy, delivery, infancy, childhood and
      adolescence when calculating a risk score (RS) to adjust for needs. We classified
      the mother's country of birth according to the gross national income (GNI) per
      capita of each country. RESULTS: Overall, the lower the income of the mother's
      birth country, the lower the probability of psychotropic medication use among
      children. When adjusting for needs, the association became even stronger.
      CONCLUSIONS: Besides medical needs, use of psychotropic medication by descendants
      of immigrants seems conditioned by the socioeconomic characteristics of the
      mothers' countries of birth. The threat of information bias must be considered if
      psychotropic medication is used a proxy for impaired psychological health in
      descendants of immigrants.

PMID- 22983876
TI  - Derivation and validation of a clinical prediction rule for delirium in patients
      admitted to a medical ward: an observational study.
AB  - OBJECTIVES: To develop and validate a simple clinical prediction rule, based on
      variables easily measurable at admission, to identify patients at high risk of
      developing delirium during their hospital stay on an internal medicine ward.
      DESIGN: Prospective study of two cohorts of patients admitted between 1 May and
      30 June 2008 (derivation cohort), and between 1 May and 30 June 2009 (validation
      cohort). SETTING: A tertiary hospital in Donostia-Gipuzkoa (Spain). PARTICIPANTS:
      In total 397 patients participated in the study. The mean age and incidence of
      delirium were 75.9 years and 13%, respectively, in the derivation cohort, and
      75.8 years and 25% in the validation cohort. MAIN OUTCOME MEASURES: The
      predictive variables analysed and finally included in the rule were: being aged
      85 years old or older, being dependent in five or more activities of daily
      living, and taking two or more psychotropic drugs (antipsychotics,
      benzodiazepines, antidepressants, anticonvulsant and/or antidementia drugs). The
      variable of interest was delirium as defined by the short Confusion Assessment
      Method, which assesses four characteristics: acute onset and fluctuating course,
      inattention, disorganised thinking and altered level of consciousness. RESULTS:
      We developed a rule in which the individual risk of delirium is obtained by
      adding one point for each criterion met (age>=85, high level of dependence, and
      being on psychotropic medication). The result is considered positive if the score
      is >=1. The rule accuracy was: sensitivity=93.4% (95% CI 85.5% to 97.2%),
      specificity=60.6% (95% CI 54.1% to 66.8%), positive predictive value=44.4% (95%
      CI 36.9% to 52.1%) and negative predictive value=96.5% (95% CI: 92% to 98.5%).
      The area under the receiver operator characteristic (ROC) curve was 0.85 for the
      validation cohort. CONCLUSIONS: The presence or absence of any of the three
      predictive factors (age>=85, high level of dependence and psychotropic
      medication) allowed us to classify patients on internal medicine wards according
      to the risk of developing delirium. The simplicity of the variables in our
      clinical prediction rule means that the data collection required is feasible in
      busy medicine units.

PMID- 22983875
TI  - Validation of prescribing appropriateness criteria for older Australians using
      the RAND/UCLA appropriateness method.
AB  - OBJECTIVE: To further develop and validate previously published national
      prescribing appropriateness criteria to assist in identifying drug-related
      problems (DRPs) for commonly occurring medications and medical conditions in
      older (>=65 years old) Australians. DESIGN: RAND/UCLA appropriateness method.
      PARTICIPANTS: A panel of medication management experts were identified consisting
      of geriatricians/pharmacologists, clinical pharmacists and disease management
      advisors to organisations that produce Australian evidence-based therapeutic
      publications. This resulted in a round-one panel of 15 members, and a round-two
      panel of 12 members. MAIN OUTCOME MEASURE: Agreement on all criteria. RESULTS:
      Forty-eight prescribing criteria were rated. In the first rating round via email,
      there was disagreement regarding 17 of the criteria according to median panel
      ratings. During a face-to-face second round meeting, discussion resulted in
      retention of 25 criteria after amendments, agreement for 14 criteria with no
      changes required and deletion of 9 criteria. Two new criteria were added,
      resulting in a final validated list of 41 prescribing appropriateness criteria.
      Agreement after round two was reached for all 41 criteria, measured by median
      panel ratings and the amount of dispersion of panel ratings, based on the
      interpercentile range. CONCLUSIONS: A set of 41 Australian prescribing
      appropriateness criteria were validated by an expert panel. Use of these
      criteria, together with clinical judgement and other medication review processes
      such as patient interview, is intended to assist in improving patient care by
      efficiently detecting potential DRPs related to commonly occurring medicines and
      medical conditions in older Australians. These criteria may also contribute to
      the medication management education of healthcare professionals.

PMID- 22983878
TI  - Use of reverse transcriptase polymerase chain reaction (RT-PCR) in molecular
      screening of Newcastle disease virus in poultry and free-living bird populations.
AB  - The aim of this study was to evaluate a simple molecular method of reverse
      transcriptase polymerase chain reaction (RT-PCR) to differentiate Newcastle
      disease virus strains according to their pathogenicity, in order to use it in
      molecular screening of Newcastle disease virus in poultry and free-living bird
      populations. Specific primers were developed to differentiate LaSota--LS-
      (vaccine strain) and Sao Joao do Meriti--SJM--strain (highly pathogenic strain).
      Chickens and pigeons were experimentally vaccinated/infected for an in vivo study
      to determine virus shedding in feces. Validation of sensitivity and specificity
      of the primers (SJM and LS) by experimental models used in the present study and
      results obtained in the molecular analysis of the primers by BLAST made it
      possible to generalize results. The development of primers that differentiate the
      level of pathogenicity of NDV stains is very important, mainly in countries where
      real-time RT-PCR is still not used as a routine test. These primers were able to
      determine the presence of the agent and to differentiate it according to its
      pathogenicity.

PMID- 22983879
TI  - Magnetic resonance imaging in the diagnosis and surveillance of thoracic aortic
      perigraft seroma and its complications.

PMID- 22983877
TI  - The Northern Manhattan Caregiver Intervention Project: a randomised trial testing
      the effectiveness of a dementia caregiver intervention in Hispanics in New York
      City.
AB  - OBJECTIVES: Dementia prevalence and its burden on families are increasing.
      Caregivers of persons with dementia have more depression and stress than the
      general population. Several interventions have proven efficacy in decreasing
      depression and stress in selected populations of caregivers. Hispanics in New
      York City tend to have a higher burden of dementia caregiving compared to non
      Hispanic whites (NHW) because Hispanics have a higher prevalence of dementia,
      tend to have high family involvement, and tend to have higher psychosocial and
      economic stressors. Thus, we chose to test the effectiveness of a dementia
      caregiving intervention, the New York University Caregiver Intervention (NYUCI),
      with demonstrated efficacy in spouse caregivers in Hispanic relative caregivers
      of persons with dementia. Including the community health worker (CHW)
      intervention in both arms alleviates general psychosocial stressors and allows
      the assessment of the effectiveness of the intervention. Compared to two original
      efficacy studies of the NYUCI, which included only spouse caregivers, our study
      includes all relative caregivers, including common law spouses, children,
      siblings, a nephew and nieces. This study will be the first randomised trial to
      test the effectiveness of the NYUCI in Hispanic caregivers including non-spouses.
      METHODS AND ANALYSIS: The design of the study is a randomised controlled trial
      (RCT). Participants are randomised to two arms: case management by a CHW and an
      intervention arm including the NYUCI in addition to case management by the CHW.
      The duration of intervention is 6 months. The main outcomes in the trial are
      changes in the Geriatric Depression Scale (GDS) and the Zarit Caregiver Burden
      Scale (ZCBS) from baseline to 6 months. ETHICS AND DISSEMINATION: This trial is
      approved by the Columbia University Medical Center Institutional Review Board
      (AAAI0022), and funded by the National Institute on Minority Health and Health
      Disparities. The funding agency has no role in dissemination. TRIAL REGISTRATION:
      www.ClinicalTrials.gov NCT01306695.

PMID- 22983880
TI  - Leiomyosarcoma of the inferior vena cava: radical surgery without vascular
      reconstruction.
AB  - Leiomyosarcoma of the inferior vena cava (IVC) is a rare tumor of mesenchymal
      origin, occurring most frequently in middle-aged women. Insidious complaints
      delay diagnosis, prognosis is poor, and the only curative modality remains an
      aggressive surgical resection yielding clear margins of disease. Commonly,
      radical tumor excision mandates caval repair or reconstruction, with significant
      related morbidity and mortality. We present a case of a 50-year-old woman with a
      leiomyosarcoma arising from the lower segment of the IVC, managed by surgical en
      bloc resection of the tumor and IVC segment without further caval repair or
      reconstruction. During 14 months of follow-up the patient is well, had not had
      any complications, and is disease free.

PMID- 22983881
TI  - An uncommon finding of subtle Simon's bleedings in a fatally injured skydiver.

PMID- 22983882
TI  - Dual diagnosis of sarcoidosis and lymphoma.
AB  - BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin
      with pulmonary and extrapulmonary manifestations. Worldwide it is most often
      diagnosed in the third and fourth decades and most often affects Swedish, Danish
      and black patients. The association between malignancy and sarcoidosis has not
      been conclusively proven. Cancer can eventually occur in patients who have an
      established diagnosis of sarcoidosis for example, in sarcoidosis-lymphoma
      syndrome. Sarcoidosis can also subsequently develop in an oncology patient. There
      are multiple obstacles to confirming epidemiologically the linkage between
      sarcoidosis and malignancy. Histological verification and clinical acumen are
      needed to avoid misdiagnosis. The 18 fluorodeoxyglucose (18-FDG) PET has failed
      to provide a non invasive diagnostic method to differentiate neoplasia from
      benign sarcoid lesions and tissue diagnosis is essential before commencing a new
      therapeutic intervention in patients with lymphoma. METHODS: We report 3 cases of
      co-diagnosis of sarcoidosis and lymphoma that were seen in an oncology unit in
      Drogheda, Co. Louth. RESULTS: Our patients varied in the temporal association
      between the diagnosis of sarcoidosis and lymphoma as well as their demographic
      characteristics. CONCLUSION: These cases help to demonstrate the need for careful
      clinical, histological and radiological assessment.

PMID- 22983883
TI  - Tandem synthesis of highly functionalized pyrazole derivatives from terminal
      alkynes, sulfonyl azides, diethyl azadicarboxylate, and sodium arylsulfinates.
AB  - The reaction between ketenimine intermediates [generated from terminal alkynes
      and sulfonyl azides], diethyl azadicarboxylate, and sodium arylsulfinates in N, N
      dimethylformamide at room temperature, affords ethyl 2,3-dihydro-3-oxo-4-phenyl-2
      tosyl-5-(tosylamino)pyrazole-1-carboxylates in moderate-to-good yields. When
      diisopropyl azadicarboxylate was used as the ester component, diisopropyl 1
      arylsulfonyl-2-{[aryl(alkyl)sulfonyl]-2-phenylethanimidoyl}-1,2
      hydrazinedicarboxylates were obtained.

PMID- 22983884
TI  - Current treatment of ST elevation acute myocardial infarction in Japan: door-to
      balloon time and total ischemic time from the J-AMI registry.
AB  - The door-to-balloon time and total ischemic time are important predictors of the
      outcome in patients with ST elevation myocardial infarction (STEMI) receiving
      primary angioplasty, but the current situation in Japan is unknown. The Japan
      Acute Myocardial Infarction registry is a prospective observational study of
      2,030 consecutive STEMI patients admitted to 213 Japanese institutions. The time
      from symptom onset to hospital arrival, door-to-balloon time, and in-hospital
      outcome were assessed. Data were compared between patients treated during regular
      hours or after hours. Percutaneous coronary angioplasty was done in 97.2 % of the
      patients, using drug-eluting stents in 30 % and bare metal stents in 63 % of the
      treated cases. The median symptom onset-to-door time (25th and 75th percentiles)
      was 135 min (64-305 min), median door-to-balloon time was 42 min (28-66 min), and
      mean procedural time was 98 +/- 51 min. The on-call catheterization team
      performed 48.5 % of the procedures. There was no significant difference of door
      to-balloon time between the patients treated after hours and those treated during
      regular hours. The cardiac mortality rate was 3.2 %, and it increased with longer
      door-to-balloon times (P = 0.03). The relationship between total ischemic time
      and cardiac mortality showed 2 peaks, with a trough at 5 h. Median door-to
      balloon time was <90 min and was not longer in after hours cases. These findings
      suggest that Japanese institutions can provide primary angioplasty within an
      acceptable time frame.

PMID- 22983886
TI  - Tamsulosin for voiding dysfunction in women.
AB  - PURPOSE: Lower urinary tract symptoms (LUTS) affect countless individuals
      worldwide with an increased prevalence among those>=60 years of age. As the
      world's population ages, the prevalence of LUTS will continue to increase,
      diminishing the quality of life of many men and women. For men, alpha-1
      adrenergic receptor (alpha1-AR) blockers are used as first-line therapy to
      mitigate bothersome LUTS, but for women with LUTS, few treatments have been
      adequately studied. However, new research has emerged evaluating the use of
      tamsulosin and other alpha1-AR blockers in female LUTS. Thus, the purpose of this
      review is to evaluate clinical trials using tamsulosin for the treatment of LUTS
      in women to determine if tamsulosin is an appropriate treatment option. METHODS:
      A comprehensive search of the MEDLINE (1966-May 2012) and EMBASE (1980-May 2012)
      databases was performed. Additional articles were retrieved by manual review of
      the references cited in publications from the database search. Five published
      clinical trials and two abstracts were identified. RESULTS: All seven trials
      presented in this review demonstrated statistically significant primary outcomes
      with use of tamsulosin in female LUTS, especially in women with predominant
      voiding dysfunction. Such efficacy measures included a reduction in urinary
      symptoms as well as improvements in quality of life and sleep quality. Tamsulosin
      was found to be safe and well tolerated in all studies reviewed. CONCLUSION:
      Consistent positive findings across multiple clinical studies suggest that in
      women with LUTS, particularly those with voiding dysfunction, tamsulosin may be
      an effective and safe treatment option.

PMID- 22983887
TI  - Penile vascular indices in surgically treated and conservatively treated penile
      fracture: does conventional immediate repair matter?
AB  - OBJECTIVE: To investigate the impact of immediate surgical repair and
      conservative treatment of penile fracture (PF) on penile vascular indices.
      METHODS: The study includes 146 surgically treated (group 1), and 56
      conservatively treated patients (group 2). All of the participants underwent
      penile duplex Doppler ultrasonography (PDDU), and Doppler parameters including
      the peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive
      index (RI) were measured in both corpora at baseline and after intracavernosal
      injection of 20 MUg prostaglandin E1. Univariable and multivariable Cox
      regression analysis addressed study variables. RESULTS: An increased number of
      men in group 2 (25.0%) compared with men in group 1 (19.2%) reported ED, but the
      difference did not reach statistical significance (P=0.06). In patients with ED
      the mean PSV did not differ significantly between the group 1 (30.1+/-4.02 cm/s)
      and group 2 (30.1+/-4.02 cm/s) (P=0.32). Also, in patients without ED, the mean
      PSV for group 1 (82.4+/-24.1 cm/s) subjects did not differ significantly from the
      means for the group 2 patients (79.4+/-27.2 cm/s) (P=0.21). Vascular hemodynamics
      in fractured corpus cavernosum did not differ significantly between two groups
      (P=0.08). CONCLUSIONS: Current method of surgical treatment does not provide
      better outcome in terms of erectile function and penile vascular hemodynamics.

PMID- 22983888
TI  - Variations in carbachol- and ATP-induced contractions of the rat detrusor:
      effects of gender, mucosa and contractile direction.
AB  - PURPOSE: Contractile characteristics of the bladder may depend on variables such
      as gender, mucosa (MU) and direction of the contractions. However, definitive
      information is not yet available despite earlier studies on the effects of one
      variable or another. Here, we explored the differences in the rat detrusor
      attributable to gender, mucosa and contractile direction. METHODS: K+, carbachol
      (CCh) and ATP were used as contractile stimuli on rat detrusor strips with and
      without MU. Contractility was monitored using a myograph system. Both tonic and
      phasic contractile activities were analyzed. RESULTS: MU-independent contractions
      induced by CCh were more potent in females, an effect specific to the
      longitudinal direction only. The maximal CCh response was larger also in females
      when MU was removed, suggesting a stronger MU-independent component in the
      contraction. The larger area under curves of the females under ATP stimulation
      showed dependence on MU and contractile direction as well. ATP-induced
      contractions in the males were affected more by MU in the transverse direction
      than in the females. Direction- and MU-dependent variability of ATP responses was
      also observed in the males but not in females. CONCLUSIONS: Findings here added
      new information to the understanding of bladder contractile physiology, providing
      insights into the quest for better drugs in managing bladder disorders.

PMID- 22983889
TI  - Giant basilar artery aneurysm and unexpected death.

PMID- 22983890
TI  - Mexican mestizo population sub-structure: effects on genetic and forensic
      statistical parameters.
AB  - Since Mexican mestizos are an admixed population, it is necessary to determine
      the effects that the substructure of the population has on genetic and forensic
      parameters. With this aim, a study was performed with 15 STR loci (CODIS plus
      D2S1338 and D19S433) on 1,640 unrelated Mexican mestizos. We determine allele and
      genotypic frequencies observing departure from Hardy-Weinberg expectation (12 out
      of 15 loci, with an excess of homozygotes, Fis > 0), as well as pairs of loci in
      an apparent linkage disequilibrium (13 of 92 loci). We conducted a test for
      genetic population stratification, the results show that the Mexican mestizo
      population is substructured into three subgroups, which are in HW and linkage
      equilibrium. The combination of the 15 loci in the whole population has high
      forensic efficiency with the capacity to genetically discriminate one individual
      in one quintillion (1/10(18)). Our data potentially validates the use of these 15
      STR loci to establish forensic identity and parentage testing for legal purposes,
      and offers a powerful tool for genetic variation analysis. However, given that
      the population is stratified, we highly recommend applying a correction with the
      inbreeding coefficient in calculations of paternity and forensic studies to avoid
      erroneous assumptions.

PMID- 22983891
TI  - Design of non-standard insulin analogs for the treatment of diabetes mellitus.
AB  - Structure-based protein design has enabled the engineering of insulin analogs
      with improved pharmacokinetic and pharmacodynamic properties. Exploiting
      classical structures of zinc insulin hexamers, the first insulin analog products
      focused on destabilization of subunit interfaces to obtain rapid-acting
      (prandial) formulations. Complementary efforts sought to stabilize the insulin
      hexamer or promote higher-order self-assembly within the subcutaneous depot
      toward the goal of enhanced basal glycemic control with reduced risk of
      hypoglycemia. Current products either operate through isoelectric precipitation
      (insulin glargine, the active component of Lantus; Sanofi-Aventis, Paris, France)
      or employ an albumin-binding acyl tether (insulin detemir, the active component
      of Levemir; Novo-Nordisk, Basvaerd, Denmark). In the past year second-generation
      basal insulin analogs have entered clinical trials in an effort to obtain ideal
      flat 24-hour pharmacodynamic profiles. The strategies employ non-standard protein
      modifications. One candidate (insulin degludec; Novo-Nordisk a/s) undergoes
      extensive subcutaneous supramolecular assembly coupled to a large-scale
      allosteric reorganization of the insulin hexamer (the TR transition). Another
      candidate (LY2605541; Eli Lilly and Co., Indianapolis, IN, USA) utilizes coupling
      to polyethylene glycol to delay absorption and clearance. On the other end of the
      spectrum, advances in delivery technologies (such as microneedles and
      micropatches) and excipients (such as the citrate/zinc-ion chelator combination
      employed by Biodel, Inc., Danbury, CT, USA) suggest strategies to accelerate
      PK/PD toward ultra-rapid-acting insulin formulations. Next-generation insulin
      analogs may also address the feasibility of hepatoselective signaling. Although
      not in clinical trials, early-stage technologies provide a long-range vision of
      "smart insulins" and glucose-responsive polymers for regulated hormone release.

PMID- 22983892
TI  - What will diabetes genomes tell us?
AB  - A new generation of genetic studies of diabetes is underway. Following from
      initial genome-wide association (GWA) studies, more recent approaches have used
      genotyping arrays of more densely spaced markers, imputation of ungenotyped
      variants based on improved reference haplotype panels, and sequencing of protein
      coding exomes and whole genomes. Experimental and statistical advances make
      possible the identification of novel variants and loci contributing to trait
      variation and disease risk. Integration of sequence variants with functional
      analysis is critical to interpreting the consequences of identified variants. We
      briefly review these methods and technologies and describe how they will continue
      to expand our understanding of the genetic risk factors and underlying biology of
      diabetes.

PMID- 22983893
TI  - "Safe and effective when used as directed": the case of chronic use of opioid
      analgesics.
AB  - Opioid analgesics have been used increasingly over the past 20 years for the
      management of chronic non-cancer pain in the USA under the assumption that they
      were safe and effective when used as directed. The accuracy of that assumption
      has not been tested against accumulated evidence. The safety of opioids used on a
      long-term basis has not been tested in clinical trials. Epidemiologic evidence
      from examinations of such use in the general population indicates that the risk
      of overdose increases in a dose-response manner. Such evidence also suggests
      increased risk of fractures and acute myocardial infarctions among elderly users
      of opioids for chronic pain. Experimental evidence supports short-term use of
      opioids, but trials of long-term use for chronic pain have not been conducted.
      Epidemiologic evidence suggests that long-term use does not result in improvement
      in function or quality of life while being associated with significant dropout
      rates and a high prevalence of adverse drug effects. Substantial fractions of
      patients are not using opioid analgesics as directed, while millions of US
      residents are using them without a prescription for nonmedical reasons. A prudent
      treatment approach consistent with the available evidence would be to reserve
      chronic opioid therapy for serious pain-related problems for which the
      effectiveness of opioids has been demonstrated and for patients whose use as
      directed is assured through close monitoring and for whom an explicit, informed
      calculation has been made that the benefits of opioids outweigh the risks.

PMID- 22983894
TI  - Complications of long-term opioid therapy for management of chronic pain: the
      paradox of opioid-induced hyperalgesia.
AB  - While opioids remain a valid and effective analgesic strategy for patients
      suffering from a wide variety of painful conditions, they are not a panacea.
      Increasingly, physicians must balance patient expectations of adequate pain
      control with known limitations of opioid pharmaceuticals including adverse
      effects, tolerance, addiction, withdrawal, and drug diversion. Further
      complicating the issue over the last decade is a growing body of evidence
      suggesting chronic opioid use may unexpectedly worsen the perception of pain in
      some individuals. This syndrome, termed opioid-induced hyperalgesia (OIH),
      fundamentally changes our understanding of opioid pharmacodynamics and may
      influence our approach to management of chronic pain. This manuscript describes
      the concept OIH and provides an overview of basic science and clinical research
      to date attempting to characterize this syndrome, as well as ascertain its
      clinical relevance. The potential existence of OIH in humans is framed within the
      context of our current understanding of opioids and our prescribing patterns so
      that physicians may begin to incorporate these ideas into their philosophy of
      pain management as further information develops. Animal studies reliably validate
      OIH in controlled models. Rigorous research protocols in humans are lacking, and
      we cannot yet confidently conclude that OIH manifests in clinically significant
      ways. However, clinicians should consider the possibility of OIH when evaluating
      outcomes of patients on chronic opioid therapy.

PMID- 22983895
TI  - Wound closure and wound monitoring in total hip arthroplasty. An overview.
AB  - Wound closure in primary and revision total hip arthroplasty is an essential and
      crucial step of the procedure. A recently published meta-analysis comparing
      metallic staples and sutures with stitches in hip procedures revealed that the
      risk of infection was four times greater when staples were used. This statement
      created concern among orthopaedic surgeons. The aim of this overview is to
      address the problem of THA wound closure and wound monitoring. Further well
      designed, randomised, controlled trials comparing staples vs traditional stitches
      and eventually vs skin adhesive are necessary in order to draw conclusions in
      elective THA, revision surgery and hip fractures. Orthopaedic surgeons need to
      have more evidence in order to be able to justify their method of wound closure.
      Monitoring of the wound by the surgeon in the postoperative period is
      recommended.

PMID- 22983896
TI  - Mutation rate in Velvet tobacco mottle virus varies between genomic region and
      virus variant but is not influenced by obligatory mirid transmission.
AB  - Genomic mutation in plant viruses of cultivated plants is known to be influenced
      by virus, host and vector, but the factors influencing mutation in viruses of
      native plants in natural ecosystems are rarely studied. We have tested the effect
      of mode of transmission on mutation in Velvet tobacco mottle virus (VTMoV), a
      mirid-vectored sobemovirus associated with Nicotiana velutina, an Australian
      native xerophyte growing in a region isolated from anthropogenic influences. Two
      variants of VTMoV (K1 and R17) were passaged monthly in the alternative
      experimental plant host, N. clevelandii, for 2 years, either by mechanical
      inoculation or by transmission with the mirid Cyrtopeltis nicotianae. Sequence
      variations were scored after 24 passages in regions of the genome containing the
      open reading frames (ORFs) for the P1 and coat protein (CP). The mean mutation
      rate was 6.83 * 10(-4) nt/site year, but a higher overall rate was observed for
      the K1 (satellite -) than the R17 (satellite +) variant. The P1 ORF showed a
      higher frequency of non-synonymous mutations than the CP. No clear association
      was found between either mutation site or mutation rate and the mode of
      transmission, indicating that obligatory mirid transmission had not exerted a
      specific bottle-neck effect on sequence variation during the experimental time
      frame. Failure to detect any sequence motifs linked to vector transmission
      suggests that a specific capsid-stylet interaction is not required for
      transmission by mirids.

PMID- 22983897
TI  - Structural basis of metal hypersensitivity.
AB  - Metal hypersensitivity is a common immune disorder. Human immune systems mount
      the allergic attacks on metal ions through skin contacts, lung inhalation and
      metal-containing artificial body implants. The consequences can be simple
      annoyances to life-threatening systemic illness. Allergic hyper-reactivities to
      nickel (Ni) and beryllium (Be) are the best-studied human metal
      hypersensitivities. Ni-contact dermatitis affects 10 % of the human population,
      whereas Be compounds are the culprits of chronic Be disease (CBD). alphabeta T
      cells (T cells) play a crucial role in these hypersensitivity reactions. Metal
      ions work as haptens and bind to the surface of major histocompatibility complex
      (MHC) and peptide complex. This modifies the binding surface of MHC and triggers
      the immune response of T cells. Metal-specific alphabeta T cell receptors (TCRs)
      are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous
      models have been proposed, yet the mechanisms and molecular basis of metal
      hypersensitivity remain elusive. Recently, we determined the crystal structures
      of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101,
      DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual
      features of MHCII molecules and shed light on how metal ions are recognized by T
      cells.

PMID- 22983899
TI  - Gastrin receptor pharmacology.
AB  - C-terminally amidated gastrins act at cholecystokinin-2 receptors (CCK2R), which
      are normally expressed by gastric parietal and enterochromaffin-like (ECL) cells
      and smooth muscle; there is also extensive expression in the CNS where the main
      endogenous ligand is cholecystokinin. A variety of neoplasms express CCK2R, or
      splice variants, including neuroendocrine, pancreatic, medullary thyroid and lung
      cancers. Other products of the gastrin gene (progastrin, the Gly-gastrins) may
      stimulate cell proliferation but are not CCK2R ligands. Depending on the cell
      type, stimulation of CCK2R evokes secretion, increases proliferation and cell
      migration, inhibits apoptosis, and controls the expression of various genes.
      These effects are mediated by increased intracellular calcium and activation of
      protein kinase C, MAPkinase and other protein kinase cascades. There has been
      recent progress in developing CCK2R ligands that can be used for imaging tumours
      expressing the receptor. New antagonists have also been developed, and there is
      scope for using these for suppression of gastric acid and for treatment of
      neuroendocrine and other CCK2R-expressing tumours.

PMID- 22983898
TI  - Differential effects of type I and II interferons on myeloid cells and resistance
      to intracellular bacterial infections.
AB  - The type I and II interferons (IFNs) play important roles in regulating immune
      responses during viral and bacterial infections and in the context of autoimmune
      and neoplastic diseases. These two IFN types bind to distinct cell surface
      receptors that are expressed by nearly all cells to trigger signal transduction
      events and elicit diverse cellular responses. In some cases, type I and II IFNs
      trigger similar cellular responses, while in other cases, the IFNs have unique or
      antagonistic effects on host cells. Negative regulators of IFN signaling also
      modulate cellular responses to the IFNs and play important roles in maintaining
      immunological homeostasis. In this review, we provide an overview of how IFNs
      stimulate cellular responses. We discuss the disparate effects of type I and II
      IFNs on host resistance to certain intracellular bacterial infections and provide
      an overview of models that have been proposed to account for these disparate
      effects. Mechanisms of antagonistic cross talk between type I and II IFNs are
      also introduced.

PMID- 22983900
TI  - In vitro antifungal activity of micafungin and caspofungin against dermatophytes
      isolated from China.
AB  - AIMS: The aims of this study are to investigate the in vitro activities of
      micafungin and caspofungin that are two new echinocandin antifungal drugs against
      clinically isolated dermatophytes in China and to define MEC (minimal effective
      concentration) as the reading endpoints of this study in accordance with
      (Clinical and laboratory Standards Institute) CLSI M38-A2 reference. METHODS:
      Minimal effective concentrations (MECs) of micafungin and caspofungin for 82
      dermatophyte strains were determined according to CLSI (formerly NCCLS) M38-A2
      broth microdilution methods. RESULTS: (1) The MEC(90s) of micafungin for
      Trichophyton violaceum and Trichophyton tonsurans were 0.25 MUg/mL, and for
      Microsporum canis and Trichophyton verrucosum were 0.06 MUg/mL. The MEC(90s) for
      Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum gypseum and
      Epidermophyton floccosum were 0.03 MUg/mL. (2) The MEC(90s) of caspofungin for T.
      rubrum, T. violaceum and T. tonsurans were 1 MUg/mL, and for T. mentagrophytes,
      M. canis, M. gypseum, E. floccosum and T. verrucosum were 0.5 MUg/mL. (3)
      Compared with caspofungin, micafungin demonstrated lower MEC value to
      dermatophytes (P < 0.05). CONCLUSIONS: Micafungin has stronger in vitro
      antifungal activity than caspofungin.

PMID- 22983901
TI  - Penicillium marneffei infection: an emerging disease in mainland China.
AB  - Penicillium marneffei is an emerging pathogenic fungus that can cause a life
      threatening systemic mycosis in immunocompromised hosts, especially in patients
      with AIDS. This infection is endemic in Southeast Asia. With the prevalence of
      AIDS in this area, the number of patients with systemic penicilliosis marneffei
      is found to be increasing rapidly in mainland China in recent years. We recently
      reviewed 668 cases of penicilliosis marneffei in mainland China from January 1984
      to December 2009 in cnki, cqvip, CBMdisc and PubMed. We analyzed epidemiological
      and clinical features, laboratory findings, reaction to therapy and prognosis of
      the disease. We found that 99.4% of the cases were reported in the southern part
      of China; among these cases, 42.8% were from Guangxi (286 cases) and 40.6% were
      from Guangdong province (271 cases). Five hundred and eighty-six cases (87.7%) of
      penicilliosis marneffei were reported with infection by the human
      immunodeficiency virus, 25 cases (3.8%) with other immunocompromised diseases,
      and 57 cases (8.5%) without any documented underlying diseases. Fever, weight
      loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs and skin
      lesions were the common clinical manifestations of P. marneffei infections. The
      569 cases received antifungal therapy with a mortality of 24.3% (138 cases), 99
      cases who had not received antifungal therapy had a mortality of 50.6%. P.
      marneffei was an emerging pathogenic fungus and become a medical and public
      health importance in mainland China. The immunocompromised patients should pay
      more attention to P. marneffei infection in the endemic areas.

PMID- 22983902
TI  - Suppression of GSK3beta by ERK mediates lipopolysaccharide induced cell migration
      in macrophage through beta-catenin signaling.
AB  - We investigate the role of beta-catenin signaling in the response of macrophage
      to lipopolysaccharide (LPS) using RAW264.7 cells. LPS rapidly stimulated
      cytosolic beta-catenin accumulation. beta-catenin-mediated transcription was
      showed to be required for LPS induced gene expression and cell migration.
      Mechanically, ERK activation-primed GSK3beta inactivation by Akt was demonstrated
      to mediate the LPS induced beta-catenin accumulation. Overall, our findings
      suggest that suppression of GSK3beta by ERK stimulates beta-catenin signaling
      therefore contributes to LPS induced cell migration in macrophage activation.

PMID- 22983903
TI  - HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and
      activation of downstream signaling pathways.
AB  - Dimerization among the EGFR family of tyrosine kinase receptors leads to
      allosteric activation of the kinase domains of the partners. Unlike other members
      in the family, the kinase domain of HER3 lacks key amino acid residues for
      catalytic activity. As a result, HER3 is suggested to serve as an allosteric
      activator of other EGFR family members which include EGFR, HER2 and HER4. To
      study the role of intracellular domains in HER3 dimerization and activation of
      downstream signaling pathways, we constructed HER3/HER2 chimeric receptors by
      replacing the HER3 kinase domain (HER3-2-3) or both the kinase domain and the C
      terminal tail (HER3-2-2) with the HER2 counterparts and expressed the chimeric
      receptors in Chinese hamster ovary (CHO) cells. While over expression of the
      intact human HER3 transformed CHO cells with oncogenic properties such as AKT/ERK
      activation and increased proliferation and migration, CHO cells expressing the
      HER3-2-3 chimeric receptor showed significantly reduced HER3/HER2 dimerization
      and decreased phosphorylation of both AKT and ERK1/2 in the presence of
      neuregulin-1 (NRG-1). In contrast, CHO cells expressing the HER3-2-2 chimeric
      receptor resulted in a total loss of downstream AKT activation in response to NRG
      1, but maintained partial activation of ERK1/2. The results demonstrate that the
      intracellular domains play a crucial role in HER3's function as an allosteric
      activator and its role in downstream signaling.

PMID- 22983904
TI  - Aptamer-based molecular imaging.
AB  - Molecular imaging has greatly advanced basic biology and translational medicine
      through visualization and quantification of single/multiple molecular events
      temporally and spatially in a cellular context and in living organisms. Aptamers,
      short single-stranded nucleic acids selected in vitro to bind a broad range of
      target molecules avidly and specifically, are ideal molecular recognition
      elements for probe development in molecular imaging. This review summarizes the
      current state of aptamer-based biosensor development (probe design and imaging
      modalities) and their application in imaging small molecules, nucleic acids and
      proteins mostly in a cellular context with some animal studies. The article is
      concluded with a brief discussion on the perspective of aptamer-based molecular
      imaging.

PMID- 22983905
TI  - Comparative antibacterial activity of a novel semisynthetic antibiotic: etimicin
      sulphate and other aminoglycosides.
AB  - Etimicin is a novel fourth generation semisynthetic aminoglycoside. It has good
      antimicrobial activity against both gram-positive and gram-negative bacterial
      infections and also against aminoglycoside resistant strains. In the present
      study, in vitro antibacterial activity of etimicin was determined by minimum
      inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time
      kill curve tests against type strains and 407 clinical isolates (obtained in a
      surveillance study), in comparison to other aminoglycosides. Test results
      revealed that etimicin has potential antimicrobial activity and MIC, MBC values
      for etimicin were low compared to other aminoglycosides. In MBC test etimicin has
      exhibited potential bactericidal effect ranging from 0.25 to 2 mg/L. The time
      kill-curve study further demonstrated the rapid, concentration dependent killing
      and comparative study showed etimicin to exhibit long and effective bactericidal
      activity over amikacin. The interesting fact is that most of the tested
      aminoglycoside resistant clinical isolates were susceptible to etimicin. In view
      of its potent in vitro antibacterial activity and efficacy profiles, it can be
      concluded that etimicin can be a potent injectable agent for the treatment of
      severe bacterial infections.

PMID- 22983906
TI  - Mapping I-A(g7) restricted epitopes in murine G6PC2.
AB  - G6PC2, also known as islet-specific glucose 6-phosphatase catalytic subunit
      related protein (IGRP), is a major target of autoreactive CD8(+) T cells in both
      diabetic human subjects and the non-obese diabetic (NOD) mouse. However, in
      contrast to the abundant literature regarding the CD8(+) response to this
      antigen, much less is known about the potential involvement of IGRP-reactive
      CD4(+) T cells in diabetogenesis. The single previous study that examined this
      question in NOD mice was based upon a candidate epitope approach and identified
      three I-A(g7)-restricted epitopes that each elicited spontaneous responses in
      these animals. However, given the known inaccuracies of MHC class II epitope
      prediction algorithms, we hypothesized that additional specificities might also
      be targeted. To address this issue, we immunized NOD mice with membranes from
      insect cells overexpressing full-length recombinant mouse IGRP and measured
      recall responses of purified CD4(+) T cells using a library of overlapping
      peptides encompassing the entire 355-aa primary sequence. Nine peptides
      representing 8 epitopes gave recall responses, only 1 of which corresponded to
      any of the previously reported sequences. In each case proliferation was blocked
      by a monoclonal antibody to I-A(g7), but not the appropriate isotype control.
      Consistent with a role in diabetogenesis, proliferative responses to 4 of the 9
      peptides (3 epitopes) were also detected in CD4(+) T cells purified from the
      pancreatic draining lymph nodes of pre-diabetic female animals, but not from
      peripheral lymph nodes or spleens of the same animals. Intriguingly, one of the
      newly identified spontaneously reactive epitopes (P8 [IGRP(55-72)]) is highly
      conserved between mice and man, suggesting that it might also be a target of HLA
      DQ8-restricted T cells in diabetic human subjects, an hypothesis that we are
      currently testing.

PMID- 22983907
TI  - Assessment of ventricular remodeling in heart failure clinical trials.
AB  - Adverse remodeling involves a complicated process of structural and functional
      changes in the left ventricle (LV). LV remodeling is progressive and, if left
      unchecked, culminates in heart failure that portends a poor prognosis. Clinical
      trials in heart failure have employed various techniques to assess ventricular
      remodeling while focusing on therapeutic-specific strategies to halt or reverse
      remodeling. These strategies include (1) those designed to reduce wall stress by
      limiting LV dilatation and reducing LV loading conditions (nitrates and
      epicardial restraint), (2) those designed to block neurohormonal activation,
      including angiotensin converting enzyme inhibitors, angiotensin receptor
      blockers, beta-adrenergic receptor blockers, and aldosterone receptor blockers,
      (3) ionotropic agents/cardiac glycosides, and (4) cardiac resynchronization
      therapy. Strategies in development include mechanical assist devices and
      myocardial regeneration. To date, trials have demonstrated a linkage between
      indices of remodeling and clinical outcomes measures. Indices of remodeling have
      facilitated identification of targets for novel pharmaceutical agents and new
      device therapies.

PMID- 22983908
TI  - Abbreviated course of radiation therapy with concurrent temozolomide for high
      grade glioma in patients of advanced age or poor functional status.
AB  - Elderly or frail patients with high-grade gliomas (HGG) can be effectively
      treated with an abbreviated course of radiation therapy (RT) consisting of 40 Gy
      in 15 fractions. Concurrent temozolomide (TMZ) improves survival in non-elderly
      patients with glioblastoma treated with standard schedule of 60 Gy in 30
      fractions. We describe our institutional experience of combining abbreviated RT
      with concurrent TMZ for treatment of HGG. Between 1/1/2004 and 2/5/2010 31
      patients were treated. Survival was estimated with the Kaplan-Meier method.
      Toxicity was scored according to CTCAE 3.0. Median age was 66 years (range 32
      90), and 17 patients had Karnofsky performance score <70. At the time of
      analysis, 30 patients (98 %) had died, with a followup of 14 months in the
      surviving patient. Median survival was 11 months (range 1-20), and 41 % of
      patients were alive at 12 months. Thirty patients (97 %) had a decreased
      corticosteroid requirement after completion of therapy. Only one new
      hospitalization for worsening neurologic status was required during therapy.
      Grade 3-4 hematologic toxicity occurred in 11 patients. Abbreviated RT with
      concurrent TMZ provides a clinical benefit, is safe and tolerable in patients of
      advanced age or poor functional status.

PMID- 22983909
TI  - Traumatic injuries of thigh and calf muscles in athletes: role and clinical
      relevance of MR imaging and ultrasound.
AB  - OBJECTIVES: Magnetic resonance (MR) imaging and ultrasound have become valuable
      tools for evaluation of traumatic muscle injuries in athletes. Common athletic
      injuries include strain, contusion and avulsion, which are characterised by
      muscle fibre disruption, intramuscular haemorrhagic dissection, haematoma at the
      musculotendinous junction, and perifascial blood or haematoma. METHODS: MR
      imaging may allow clinicians to predict the time required before athletes can
      return to competition and the risk of injury recurrence. RESULTS: Fluid-sensitive
      MR sequences, e.g., fat-suppressed T2-weighted or proton density-weighted turbo
      spin echo (TSE), and short-tau inversion recovery (STIR) sequences are suitable
      for detecting oedematous changes in the musculotendinous unit, and for
      delineating intramuscular or perifascial fluid collections or haematoma. T1
      weighted spin echo sequences are used to visualise atrophy and fatty infiltration
      and to differentiate between haemorrhage/haematoma and oedema. While ultrasound
      may play a role as an adjunctive imaging method, it is less accurate than MR
      images for assessing the extent of the injury and it cannot differentiate between
      new and old injuries. CONCLUSIONS: In this pictorial review, imaging features of
      lower extremity muscle injuries including strain, contusion and avulsion are
      reviewed, focusing on MR and ultrasound imaging findings after initial injury and
      during follow-up, and their relevance in clinical practice is discussed. TEACHING
      POINTS: * MR imaging may allow clinicians to predict time required before
      athletes can return to competition * Fluid-sensitive MR sequences are suitable
      for detecting oedematous changes in the muscles * T1-weighted sequences are used
      to differentiate between haemorrhage/haematoma and oedema. * Ultrasound can also
      be used but is less accurate than MR imaging for assessing the extent of the
      injury.

PMID- 22983910
TI  - Transcatheter Valve Treatment Pilot Registry: design and current status.

PMID- 22983911
TI  - Molecular imaging to identify the vulnerable plaque--from basic research to
      clinical practice.
AB  - Cardiovascular disease (CVD) is still the leading cause of death in the Western
      World. Adverse outcomes of CVD include stroke, myocardial infarction, and heart
      failure. Atherosclerosis is considered to be the major cause of CVD and is
      estimated to cause half of all deaths in developed countries. Atherosclerotic
      lesions of the vessel wall may obstruct blood flow mechanically through stenosis,
      but rupture of atherosclerotic plaques causing formation of occlusive thrombi is
      far more prevalent. Unfortunately, conventional diagnostic tools fail to assess
      whether a plaque is vulnerable to rupture. Research over the past decade
      identified the biological processes that are implicated in the course towards
      plaque rupture, like cell death and inflammation. Knowledge about plaque biology
      propelled the development of imaging techniques that target biologic processes in
      order to predict the vulnerable plaque. This paper discusses novel and existing
      molecular imaging targets and addresses advantages and disadvantages of these
      targets and respective imaging techniques in respect of clinical application and
      socio-economic impact.

PMID- 22983914
TI  - beta-Cell mass imaging with DTBZ positron emission tomography: is it possible?

PMID- 22983913
TI  - Epstein-barr virus and the pathogenesis of T and NK lymphoma: a mystery unsolved.
AB  - The potent growth-transforming properties of Epstein-Barr virus (EBV) and its
      role in pathogenesis of a range of B cell and epithelial malignancies are well
      established. By contrast, the association of this B lymphotropic virus with
      malignancies of T and NK cell origin was entirely unexpected. Although a number
      of mature T and NK lymphoma subtypes have been associated with EBV, evidence for
      a robust viral/tumour relationship is principally limited to extranodal NK/T
      lymphoma (ENKTL). Despite progress in diagnosis and classification, alongside an
      evolving understanding of ENKTL pathobiology, EBV's contribution to
      lymphomagenesis remains largely unresolved. Challenges relate to the rarity of
      this entity, a lack of clinical and biological correlative data and scarcity of
      fresh tissue for molecular and functional studies. Nonetheless, recent studies on
      viral and cellular gene expression have permitted new avenues of investigation
      into ENKTL pathobiology aiming to extend our understanding of disease biology and
      ultimately improve clinical outcomes.

PMID- 22983912
TI  - Microdomains in forebrain spines: an ultrastructural perspective.
AB  - Glutamatergic axons in the mammalian forebrain terminate predominantly onto
      dendritic spines. Long-term changes in the efficacy of these excitatory synapses
      are tightly coupled to changes in spine morphology. The reorganization of the
      actin cytoskeleton underlying this spine "morphing" involves numerous proteins
      that provide the machinery needed for adaptive cytoskeletal remodeling. Here, we
      review recent literature addressing the chemical architecture of the spine,
      focusing mainly on actin-binding proteins (ABPs). Accumulating evidence suggests
      that ABPs are organized into functionally distinct microdomains within the spine
      cytoplasm. This functional compartmentalization provides a structural basis for
      regulation of the spinoskeleton, offering a novel window into mechanisms
      underlying synaptic plasticity.

PMID- 22983917
TI  - Concomitant mitral valve surgery in patients undergoing surgical ventricular
      reconstruction for ischaemic cardiomyopathy.
AB  - OBJECTIVES: Ischaemic mitral valve regurgitation is associated with a significant
      reduction in survival and its treatment in patients undergoing surgical
      ventricular reconstruction is usually associated with higher perioperative
      morbidity and mortality. We evaluated our 11-year experience in this cohort of
      patients. METHODS: Between January 2000 and December 2010, a total of 282
      patients underwent surgical ventricular reconstruction, of which 45 (16%) had
      concomitant mitral valve surgery. The data was retrospectively analyzed to
      identify variables that could predict early mortality. RESULTS: Overall in
      hospital mortality was 6.4% (n = 18), of which 5.1% (n = 12) occurred in patients
      undergoing surgical ventricular reconstruction and 13.3% (n = 6) in patients
      undergoing surgical ventricular reconstruction + mitral valve surgery (P = 0.05).
      Patients undergoing surgical ventricular reconstruction + mitral valve surgery
      had poorer LV function (P < 0.01) and advanced NYHA class IV symptoms (P = 0.02)
      compared with patients undergoing surgical ventricular reconstruction. These
      patients had a higher requirement for postoperative inotropic (P < 0.01) and IABP
      support (P < 0.01) and were more likely to suffer from low cardiac output
      syndrome (P < 0.01). In patients undergoing surgical ventricular reconstruction +
      mitral valve surgery, 34 patients had mitral valve repair and 11 patients had
      mitral valve replacement. The mortality was 17.6% (n = 6) vs 0% (P = 0.31) in the
      mitral valve repair vs mitral valve replacement groups, respectively. The cohort
      of patients undergoing surgical ventricular reconstruction + mitral valve repair
      had poorer LV function and more advanced symptoms. CONCLUSIONS: Patients
      undergoing surgical ventricular reconstruction have excellent early outcomes.
      However, there are patients that are at an increased operative risk, such as
      those with concomitant ischaemic mitral regurgitation that might be better served
      with other surgical modalities, such as ventricular assist device or heart
      transplantation. The suggested algorithm based on current evidence provides a
      stepwise approach when dealing with patients with ischaemic mitral regurgitation
      +/- left ventricular remodelling.

PMID- 22983916
TI  - Function and dysfunction of alpha-synuclein: probing conformational changes and
      aggregation by single molecule fluorescence.
AB  - The aggregation and deposition of the neuronal protein alpha-synuclein in the
      substantia nigra region of the brain is a key pathological feature of Parkinson's
      disease. alpha-Synuclein assembles from a monomeric state in solution, which
      lacks stable secondary and tertiary contacts, into highly structured fibrillar
      aggregates through a pathway which involves the population of multiple oligomeric
      species over a range of time scales. These features make alpha-synuclein well
      suited for study with single-molecule techniques, which are particularly useful
      for characterizing dynamic, heterogeneous samples. Here, we review the current
      literature featuring single-molecule fluorescence studies of alpha-synuclein and
      discuss how these studies have contributed to our understanding of both its
      function and its role in disease.

PMID- 22983919
TI  - Circulating immunogenic cell death biomarkers HMGB1 and RAGE in breast cancer
      patients during neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy in breast cancer patients aims at preoperative reduction
      of tumor volume for better resection results and prognosis. As not all patients
      respond to neoadjuvant therapy, predictive biomarkers are needed for more
      efficient individual management. In prospectively collected sera of 51
      consecutive locally confined breast cancer (LBC) patients receiving preoperative,
      neoadjuvant chemotherapy, value level kinetics of soluble high mobility group box
      1 (HMGB1), soluble receptor for advanced glycation end products (sRAGE) as well
      as the established breast cancer biomarkers CA 15-3 and carcinoembryonic antigen
      (CEA) were investigated and correlated with therapy response objectified by
      pathological staging at surgery. In addition, biomarkers were measured in sera of
      30 healthy controls (HC), 13 patients with benign breast diseases, and 28
      metastatic breast cancer (MBC) patients. Pretherapeutic levels of soluble HMGB1
      were decreased in MBC, while sRAGE was already decreased in LBC. In contrast, CA
      15-3 and CEA were strongly elevated in MBC, but not in LBC. Combination of sRAGE
      and CA 15-3 enabled best discrimination of LBC from HC (AUC 78.2 %; sens 58 % at
      95 % spec), while CA15-3 and CEA discriminated best between MBC and all controls
      (AUC 90.9 %; sens 70 % at 95 % spec). In LBC patients undergoing neoadjuvant
      chemotherapy, nine patients achieved complete remission (CR), 29 achieved partial
      remission (PR), while 13 had no change of disease (NC). NC patients tended to
      have higher HMGB1 and lower sRAGE levels before therapy onset (p = 0.056 and p =
      0.054), while CA 15-3 and CEA did not predict therapeutic outcome. Furthermore,
      kinetics of HMGB1 during therapy correlated with efficacy of the treatment (p =
      0.053). Markers of immunogenic cell death are valuable for the diagnosis of MBC
      and early estimation of response to neoadjuvant therapy in LBC patients.

PMID- 22983920
TI  - PEBP4 enhanced HCC827 cell proliferation and invasion ability and inhibited
      apoptosis.
AB  - The purposes of this study were to investigate the effects of
      phosphatidylethanolamine-binding protein 4 (PEBP4) on the cell growth,
      proliferation, apoptosis, and invasion of non-small cell lung cancer (NSCLC)
      cells and to provide evidence for future treatment options for NSCLC. Western
      blot assays were performed to examine PEBP4 protein expression levels in NSCLC
      cell lines (HCC827, A549, NCI-H661, NCI-H292, and 95-D) and a normal human
      bronchial epithelial (HBE) cell line. A PEBP4 shRNA expression vector was
      constructed and transfected into HCC827 cells. Subsequently, the effects of PEBP4
      on the cell viability, cell cycle distribution, apoptosis levels, and invasion
      properties of HCC827 cells were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays, flow cytometry analyses, and transwell
      invasion assays. In addition, the effects of PEBP4 on the expression of proteins
      including cyclin D1, p53, Bcl-2, MMP-2, and MMP-9 were investigated. PEBP4 was
      highly expressed in lung cancer cells (HCC827, A549, NCI-H661, NCI-H292, and 95
      D), but its expression was low in HBE cells. Cell viability, cell proliferation,
      and invasion of HCC827 cells in the PEBP4 knockdown group were significantly
      lower than that in the negative control and blank control groups (p < 0.05), and
      there were no significant differences between the negative and blank control
      groups in terms of cell viability, cell proliferation, apoptosis, and invasion.
      In HCC827 cells, the expression levels of cyclin D1, Bcl-2, MMP-2, and MMP-9 in
      the PEBP4 knockdown group were significantly lower (p < 0.05), and the expression
      of p53 protein was significantly higher than that in the negative and blank
      control groups (p < 0.05). There were no significant differences between the
      negative and blank control groups in the expression levels of cyclin D1, p53, Bcl
      2, MMP-2, and MMP-9. In conclusion, PEBP4 enhanced HCC827 cell proliferation and
      invasion ability and inhibited apoptosis. Decreased PEBP4 expression may play a
      role in the reduced invasion ability and increased apoptosis of the human NSCLC
      cell line HCC827.

PMID- 22983915
TI  - Role of cholesterol in APP metabolism and its significance in Alzheimer's disease
      pathogenesis.
AB  - Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disorder
      believed to be initiated by accumulation of amyloid beta (Abeta)-related peptides
      derived from proteolytic processing of amyloid precursor protein (APP). Research
      over the past two decades provided a mechanistic link between cholesterol and AD
      pathogenesis. Genetic polymorphisms in genes regulating the pivotal points in
      cholesterol metabolism have been suggested to enhance the risk of developing AD.
      Altered neuronal membrane cholesterol level and/or subcellular distribution have
      been implicated in aberrant formation, aggregation, toxicity, and degradation of
      Abeta-related peptides. However, the results are somewhat contradictory and we
      still do not have a complete understanding on how cholesterol can influence AD
      pathogenesis. In this review, we summarize our current understanding on the role
      of cholesterol in regulating the production/function of Abeta-related peptides
      and also examine the therapeutic potential of regulating cholesterol homeostasis
      in the treatment of AD pathology.

PMID- 22983921
TI  - Spinal cord injury-induced osteoporosis: pathogenesis and emerging therapies.
AB  - Spinal cord injury causes rapid, severe osteoporosis with increased fracture
      risk. Mechanical unloading after paralysis results in increased osteocyte
      expression of sclerostin, suppressed bone formation, and indirect stimulation of
      bone resorption. At this time, there are no clinical guidelines to prevent bone
      loss after SCI, and fractures are common. More research is required to define the
      pathophysiology and epidemiology of SCI-induced osteoporosis. This review
      summarizes emerging therapeutics including anti-sclerostin antibodies, mechanical
      loading of the lower extremity with electrical stimulation, and mechanical
      stimulation via vibration therapy.

PMID- 22983922
TI  - p21-Activated kinase 1 is required for efficient tumor formation and progression
      in a Ras-mediated skin cancer model.
AB  - The RAS genes are the most commonly mutated oncogenes in human cancer and present
      a particular therapeutic dilemma, as direct targeting of Ras proteins by small
      molecules has proved difficult. Signaling pathways downstream of Ras, in
      particular Raf/Mek/Erk and PI3K/Akt/mTOR, are dominated by lipid and protein
      kinases that provide attractive alternate targets in Ras-driven tumors. As p21
      activated kinase 1 (Pak1) has been shown to regulate both these signaling
      pathways and is itself upregulated in many human cancers, we assessed the role of
      Pak1 in Ras-driven skin cancer. In human squamous cell carcinoma (SCC), we found
      a strong positive correlation between advanced stage and grade and PAK1
      expression. Using a mouse model of Kras-driven SCC, we showed that deletion of
      the mouse Pak1 gene led to markedly decreased tumorigenesis and progression,
      accompanied by near total loss of Erk and Akt activity. Treatment of Kras(G12D)
      mice with either of two distinct small molecule Pak inhibitors (PF3758309 and
      FRAX597) caused tumor regression and loss of Erk and Akt activity. Tumor
      regression was also seen in mice treated with a specific Mek inhibitor, but not
      with an Akt inhibitor. These findings establish Pak1 as a new target in KRAS
      driven tumors and suggest a mechanism of action through the Erk, but not the Akt,
      signaling pathway.

PMID- 22983924
TI  - Short-term topiramate treatment does not improve insulin sensitivity or secretion
      in obese insulin-resistant women.
AB  - OBJECTIVE: Long-term treatment with topiramate reduces body weight and improves
      insulin sensitivity in obese humans. Our aim was to evaluate the effect of
      topiramate treatment for 4 weeks on insulin sensitivity and secretion,
      independent of weight loss. DESIGN: Randomized, double-blind, crossover, placebo
      controlled study. METHODS: Thirteen obese (BMI 36.6 +/- 1.3 kg/m(2) (mean +/-
      s.e.m.)), insulin-resistant (homeostasis model of assessment-insulin resistance
      2.0 +/- 0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P)
      for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and beta
      cell function were assessed using a two-step hyperinsulinemic euglycemic clamp
      with stable isotopes and a hyperglycemic clamp. RESULTS: Hepatic and peripheral
      insulin sensitivities were not affected by topiramate treatment (glucose disposal
      rate (step 1 (insulin infusion rate 10 MU/M(2) per min) T: 17.5 +/- 0.8 vs P:
      18.5 +/- 1.0 MUmol/kg(LBM) per min, t=1.016, P=0.33; step 2 (insulin infusion
      rate 40 mU/m(2) per min) T: 27.9 +/- 3.2 vs P: 28.8 +/- 1.9 MUmol/kg(LBM) per
      min, t=0.418, P=0.68)). Subjects lost a small amount of weight during the
      topiramate period (T: -1.0 +/- 0.2 vs P: -0.1 +/- 0.2 kg, t=2842, P=0.15). There
      were no changes in body fat mass, blood pressure, and fasting glucose. beta-Cell
      function was not affected by topiramate as evidenced by an unaltered area under
      the curve of early (0-10 min; T: 1929.6 +/- 265.7 vs P: 2024.7 +/- 333.6 pmol/l,
      t=-0.357, P=0.73) and late (80-120 min; T: 28,017.7 +/- 5029.9 vs P: 31,567.7 +/-
      5376.2 pmol/l, t=-1.481, P=0.16) phase insulin levels during hyperglycemia. The
      use of topiramate was associated with significant side effects such as
      paresthesia, nausea, dizziness, and concentration problems. CONCLUSIONS: Low-dose
      topiramate treatment for 4 weeks, relative to placebo, had no significant effect
      on insulin sensitivity in overweight/obese adult females without established
      diabetes.

PMID- 22983925
TI  - Ghosal hematodiaphyseal dysplasia with myelofibrosis.
AB  - Diaphyseal dysplasia with refractory anemia requiring blood transfusion is a
      relatively new entity having possible autosomal recessive inheritance.
      Prednisolone therapy alleviates the need for repeated transfusion. One such case
      is being reported here. 

PMID- 22983926
TI  - Antrochoanal polyp presenting as obstructive sleep apnea.
AB  - Antrochoanal polyps (ACPS) are uncommon in children presenting to the pediatric
      clinic. They commonly present with unilateral nasal obstruction. ACPS presenting
      as obstructive sleep apnea (OSA) in a young child is an uncommon initial
      presentation. A high level of suspicion is needed to diagnose OSA in young
      children as the presenting symptoms may be nonspecific and sometimes misleading. 

PMID- 22983927
TI  - Which vitamin D oral supplement is best for postmenopausal women?
AB  - Next to a healthy calcium and protein rich diet and exercise, vitamin D
      supplementation is a key pillar of osteoporosis prevention among postmenopausal
      women. This article reviews the recent recommendations on vitamin D by the IOF
      (2010), the Institute of Medicine (2010), and the US Endocrine Society (2011),
      including the evidence to support these recommendations for fracture and fall
      prevention. The recent recommendations agree that supplementation should be
      performed with vitamin D3 or vitamin D2, and that a minimal serum 25
      hydroxyvitamin D threshold of 50 nmol/l (20 ng/ml)should be achieved to overcome
      vitamin D deficiency. In contrast to the Institute of Medicine, the IOF and the
      US Endocrine Society recommend vitamin D also for the prevention of falls, and
      state that for fracture prevention a higher serum 25-hydroxyvitamin D threshold
      of 75 nmol/l (30 ng/ml) should be targeted.

PMID- 22983928
TI  - Solid-state NMR 13C and 15N resonance assignments of a seven-transmembrane
      helical protein Anabaena Sensory Rhodopsin.
AB  - Anabaena Sensory Rhodopsin (ASR) is a unique microbial rhodopsin that displays
      photocromism, interacts with soluble transducer, and may be involved in gene
      regulation. Here we report nearly complete spectroscopic (13)C and (15)N
      assignments of ASR reconstituted in lipids, obtained using two- and three
      dimensional magic angle spinning solid state NMR spectroscopy on alternately
      (13)C labeled samples. The obtained chemical shifts are used to characterize the
      protein backbone conformation. They suggest that lipid-reconstituted ASR has a
      fold generally similar to that seen in earlier X-ray studies, but with a number
      of important differences. SSNMR detects double conformations for a number of
      residues on the cytoplasmic side. 

PMID- 22983930
TI  - Preoperative predictors for noncopers to pass return to sports criteria after ACL
      reconstruction.
AB  - Less than 50% of athletes pass criteria to return to sports (RTS) 6 months after
      ACL reconstruction (ACLR). Using data on 38 noncopers, we hypothesized that
      preoperative age, quadriceps strength index (QI), and knee flexion moments (KFM)
      during gait would predict the ability to pass/fail RTS criteria and that
      preoperative quadriceps strength gains would be predictive of passing RTS
      criteria. Gait analysis and strength data were collected before and after a
      preoperative intervention and 6 months after ACLR. Age, QI, and KFM each
      contributed to the predictability to pass or fail RTS criteria 6 months after
      ACLR. Collectively, the variables predict 69% who would pass and 82% who would
      fail RTS criteria 6 months after ACLR. Younger athletes who have symmetrical
      quadriceps strength and greater KFM were more likely to pass RTS criteria.
      Further, 63% of those who increased preoperative quadriceps strength passed RTS
      criteria, whereas 73% who did not failed. Increasing quadriceps strength in
      noncopers before ACLR seems warranted.

PMID- 22983942
TI  - Limb dominance related to the variability and symmetry of the vertical ground
      reaction force and center of pressure.
AB  - The notion of limb dominance has been commonly used in the upper extremity, yet
      the two lower extremities are often treated as equal for analytical purposes.
      Attempts to determine the effects of limb laterality on gait have produced
      conflicting results. The purpose of this study was to determine if limb dominance
      affects the vertical ground reaction force and center of pressure (COP) during
      able-bodied gait. The Parotec system (Paromed GmbH, Germany) was used to collect
      plantar foot pressure data. Fifteen subjects volunteered to participate in this
      study. The coefficient of variation of the COP displacement in the mediolateral
      direction and the variability of peak force beneath the lateral forefoot in the
      nondominant foot were significant greater than in the dominant foot. Moreover,
      COP velocity in the anterior-posterior direction during the terminal stance phase
      showed greater value in the dominant foot. Our study provides support for limb
      laterality by showing limb dominance affected the vertical ground reaction force
      and center of pressure during walking gait. This finding suggests it is an
      important issue in movement science for clinicians and would assist in improving
      sports performance and rehabilitation program.

PMID- 22983931
TI  - Unilateral stance strategies of athletes with ACL deficiency.
AB  - Aberrant movement strategies are characteristic of ACL-deficient athletes with
      recurrent knee instability (noncopers), and may instigate premature or accelerate
      joint degradation. Biomechanical evaluation of kinematic changes over time may
      elucidate noncopers' responses to neuromuscular intervention and ACL
      reconstruction (ACLR). Forty noncopers were randomized into a perturbation group
      or a strength training only group. We evaluated the effects of perturbation
      training, and then gender on knee angle and tibial position during a unilateral
      standing task before and after ACLR. No statistically significant interactions
      were found. Before surgery, the strength training only group demonstrated knee
      angle asymmetry, but 6 months after ACLR, both groups presented with similar knee
      flexion between limbs. Aberrant and asymmetrical tibial position was found only
      in females following injury and ACLR. Neither treatment group showed distinct
      unilateral standing strategies following intervention; however, males and female
      noncopers appear to respond uniquely to physical therapy and surgery.

PMID- 22983944
TI  - A very complex congenital heart anomaly: diagnosis through cardiac CT.

PMID- 22983943
TI  - Bipolar disorder and alcohol use disorder: a review.
AB  - Bipolar disorder and alcohol use disorder represent a significant comorbid
      population, which is significantly worse than either diagnosis alone in
      presentation, duration, co-morbidity, cost, suicide rate, and poor response to
      treatment. They share some common characteristics in relation to genetic
      background, neuroimaging findings, and some biochemical findings. They can be
      treated with separate care, or ideally some form of integrated care. There are a
      number of pharmacotherapy trials, and psychotherapy trials that can aid program
      development. Post-treatment prognosis can be influenced by a number of factors
      including early abstinence, baseline low anxiety, engagement with an aftercare
      program and female gender. The future development of novel therapies relies upon
      increased psychiatric and medical awareness of the co-morbidity, and further
      research into novel therapies for the comorbid group.

PMID- 22983950
TI  - One hundred twenty years of koala retrovirus evolution determined from museum
      skins.
AB  - Although endogenous retroviruses are common across vertebrate genomes, the koala
      retrovirus (KoRV) is the only retrovirus known to be currently invading the germ
      line of its host. KoRV is believed to have first infected koalas in northern
      Australia less than two centuries ago. We examined KoRV in 28 koala museum skins
      collected in the late 19th and 20th centuries and deep sequenced the complete
      proviral envelope region from five northern Australian specimens. Strikingly,
      KoRV env sequences were conserved among koalas collected over the span of a
      century, and two functional motifs that affect viral infectivity were fixed
      across the museum koala specimens. We detected only 20 env polymorphisms among
      the koalas, likely representing derived mutations subject to purifying selection.
      Among northern Australian koalas, KoRV was already ubiquitous by the late 19th
      century, suggesting that KoRV evolved and spread among koala populations more
      slowly than previously believed. Given that museum and modern koalas share nearly
      identical KoRV sequences, it is likely that koala populations, for more than a
      century, have experienced increased susceptibility to diseases caused by viral
      pathogenesis.

PMID- 22983951
TI  - Purifying selection in mammalian mitochondrial protein-coding genes is highly
      effective and congruent with evolution of nuclear genes.
AB  - The mammalian mitochondrial genomes differ from the nuclear genomes by maternal
      inheritance, absence of recombination, and higher mutation rate. All these
      differences decrease the effective population size of mitochondrial genome and
      make it more susceptible to accumulation of slightly deleterious mutations. It
      was hypothesized that mitochondrial genes, especially in species with low
      effective population size, irreversibly degrade leading to decrease of organismal
      fitness and even to extinction of species through the mutational meltdown. To
      interrogate this hypothesis, we compared the purifying selections acting on the
      representative set of mitochondrial (potentially degrading) and nuclear
      (potentially not degrading) protein-coding genes in species with different
      effective population size. For 21 mammalian species, we calculated the ratios of
      accumulation of slightly deleterious mutations approximated by Kn/Ks separately
      for mitochondrial and nuclear genomes. The 75% of variation in Kn/Ks is explained
      by two independent variables: type of a genome (mitochondrial or nuclear) and
      effective population size of species approximated by generation time. First, we
      observed that purifying selection is more effective in mitochondria than in the
      nucleus that implies strong evolutionary constraints of mitochondrial genome.
      Mitochondrial de novo nonsynonymous mutations have at least 5-fold more harmful
      effect when compared with nuclear. Second, Kn/Ks of mitochondrial and nuclear
      genomes is positively correlated with generation time of species, indicating
      relaxation of purifying selection with decrease of species-specific effective
      population size. Most importantly, the linear regression lines of mitochondrial
      and nuclear Kn/Ks's from generation times of species are parallel, indicating
      congruent relaxation of purifying selection in both genomes. Thus, our results
      reveal that the distribution of selection coefficients of de novo nonsynonymous
      mitochondrial mutations has a similar shape with the distribution of de novo
      nonsynonymous nuclear mutations, but its mean is five times smaller. The harmful
      effect of mitochondrial de novo nonsynonymous mutations triggers highly effective
      purifying selection, which maintains the fitness of the mammalian mitochondrial
      genome.

PMID- 22983953
TI  - Requirement and functional redundancy of Ib subgroup bHLH proteins for iron
      deficiency responses and uptake in Arabidopsis thaliana.
AB  - The Ib subgroup of the bHLH gene family in Arabidopsis contains four members
      (AtbHLH38, AtbHLH39, AtbHLH100, and AtbHLH101). AtbHLH38 and AtbHLH39 were
      previously confirmed to interact with FER-like iron deficiency induced
      transcription factor (FIT), directly functioning in activation of the expression
      of ferric-chelate reductase FRO2 and high-affinity ferrous iron transporter IRT1.
      In this work, we characterized the functions of AtbHLH100 and AtbHLH101 in the
      regulation of the iron-deficiency responses and uptake. Yeast two-hybrid analysis
      and bimolecular fluorescence complementation assay demonstrated that both
      AtbHLH100 and AtbHLH101 could interact with FIT. Dual expression of either
      AtbHLH100 or AtbHLH101 with FIT in yeast cells activated the GUS expression
      driven by promoters of FRO2 and IRT1. The plants overexpressing FIT together with
      AtbHLH101 showed constitutive expression of FRO2 and IRT1 in roots, and
      accumulated more iron in shoots. Further, the single, double, and triple knockout
      mutants of AtbHLH38, AtbHLH39, AtbHLH100, and AtbHLH101 were generated and
      characterized. The FRO2 and IRT1 expression in roots and the iron content in
      shoots were more drastically decreased in the triple knockout mutant of AtbHLH39,
      AtbHLH100, and AtbHLH101 than that of the other available double and triple
      mutants of the four genes. Comparison of the physiological responses as well as
      the expression of FRO2 and IRT1 in the multiple knockout mutants under iron
      deficiency revealed that AtbHLH100, AtbHLH38, AtbHLH101, and AtbHLH39 played the
      gradually increased important role in the iron-deficiency responses and uptake.
      Taken all together, we conclude that the four Ib subgroup bHLH proteins are
      required and possess redundant functions with differential significance for
      activation of iron-deficiency responses and uptake in Arabidopsis.

PMID- 22983952
TI  - Functional characterization of bitter-taste receptors expressed in mammalian
      testis.
AB  - Mammalian spermatogenesis and sperm maturation are susceptible to the effects of
      internal and external factors. However, how male germ cells interact with and
      respond to these elements including those potentially toxic substances is poorly
      understood. Here, we show that many bitter-taste receptors (T2rs), which are
      believed to function as gatekeepers in the oral cavity to detect and innately
      prevent the ingestion of poisonous bitter-tasting compounds, are expressed in
      mouse seminiferous tubules. Our in situ hybridization results indicate that Tas2r
      transcripts are expressed postmeiotically. Functional analysis showed that mouse
      spermatids and spermatozoa responded to both naturally occurring and synthetic
      bitter-tasting compounds by increasing intracellular free calcium concentrations,
      and individual male germ cells exhibited different ligand-activation profiles,
      indicating that each cell may express a unique subset of T2r receptors. These
      calcium responses could be suppressed by a specific bitter-tastant blocker or
      abolished by the knockout of the gene for the G protein subunit alpha-gustducin.
      Taken together, our data strongly suggest that male germ cells, like taste bud
      cells in the oral cavity and solitary chemosensory cells in the airway, utilize
      T2r receptors to sense chemicals in the milieu that may affect sperm behavior and
      fertilization.

PMID- 22983954
TI  - Kinetochore KMN network gene CASC5 mutated in primary microcephaly.
AB  - Several genes expressed at the centrosome or spindle pole have been reported to
      underlie autosomal recessive primary microcephaly (MCPH), a neurodevelopmental
      disorder consisting of an important brain size reduction present since birth,
      associated with mild-to-moderate mental handicap and no other neurological
      feature nor associated malformation. Here, we report a mutation of CASC5 (aka
      Blinkin, or KNL1, or hSPC105) in MCPH patients from three consanguineous
      families, in one of which we initially reported the MCPH4 locus. The combined
      logarithm of odds score of the three families was >6. All patients shared a very
      rare homozygous mutation of CASC5. The mutation induced skipping of exon 18 with
      subsequent frameshift and truncation of the predicted protein. CASC5 is part of
      the KMN network of the kinetochore and is required for proper microtubule
      attachment to the chromosome centromere and for spindle-assembly checkpoint (SAC)
      activation during mitosis. Like MCPH gene ASPM, CASC5 is upregulated in the
      ventricular zone (VZ) of the human fetal brain. CASC5 binds BUB1, BUBR1, ZWINT-1
      and interestingly it binds to MIS12 through a protein domain which is truncated
      by the mutation. CASC5 localized at the equatorial plate like ZWINT-1 and BUBR1,
      while ASPM, CEP152 and PCTN localized at the spindle poles in our patients and in
      controls. Comparison of primate and rodent lineages indicates accelerated
      evolution of CASC5 in the human lineage. Our data provide strong evidence for
      CASC5 as a novel MCPH gene, and underscore the role of kinetochore integrity in
      proper volumetric development of the human brain.

PMID- 22983955
TI  - Exome sequencing and complex disease: practical aspects of rare variant
      association studies.
AB  - Genetic association and linkage studies can provide insights into complex disease
      biology, guiding the development of new diagnostic and therapeutic strategies.
      Over the past decade, genetic association studies have largely focused on common,
      easy to measure genetic variants shared between many individuals. These common
      variants typically have subtle functional consequence and translating the
      resulting association signals into biological insights can be challenging. In the
      last few years, exome sequencing has emerged as a cost-effective strategy for
      extending these studies to include rare coding variants, which often have more
      marked functional consequences. Here, we provide practical guidance in the design
      and analysis of complex trait association studies focused on rare, coding
      variants.

PMID- 22983956
TI  - Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane
      potential and defective respiration in Pank2 knock-out mouse model.
AB  - Neurodegeneration with brain iron accumulation (NBIA) comprises a group of
      neurodegenerative disorders characterized by high brain content of iron and
      presence of axonal spheroids. Mutations in the PANK2 gene, which encodes
      pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A
      metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN
      is characterized by dystonia, dysarthria, rigidity and pigmentary retinal
      degeneration. The pathogenesis of this disorder is poorly understood and,
      although PANK2 is a mitochondrial protein, perturbations in mitochondrial
      bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN
      exhibits retinal degeneration and azoospermia, but lacks any neurological
      phenotype. The absence of a clinical phenotype has partially been explained by
      the different cellular localization of the human and murine PANK2 proteins. Here
      we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to
      its human orthologue. Moreover, we show that Pank2-defective neurons derived from
      KO mice have an altered mitochondrial membrane potential, a defect further
      corroborated by the observations of swollen mitochondria at the ultra-structural
      level and by the presence of defective respiration.

PMID- 22983957
TI  - Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long
      term continuous positive airway pressure treatment: a prospective observational
      study.
AB  - RATIONALE: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular
      death in middle-aged subjects, but it is not known whether it is also a risk
      factor in the elderly. OBJECTIVES: To investigate whether OSA is a risk factor
      for cardiovascular death and to assess whether continuous positive airway
      pressure (CPAP) treatment is associated with a change in risk in the elderly.
      METHODS: Prospective, observational study of a consecutive cohort of elderly
      patients (>=65 yr) studied for suspicion of OSA between 1998 and 2007. Patients
      with an apnea-hypopnea index (AHI) less than 15 were the control group. OSA was
      defined as mild to moderate (AHI, 15-29) or severe (AHI, >=30). Patients with OSA
      were classified as CPAP-treated (adherence >= 4 h/d) or untreated (adherence < 4
      h/d or not prescribed). Participants were monitored until December 2009. The end
      point was cardiovascular death. A multivariate Cox survival analysis was used to
      determine the independent impact of OSA and CPAP treatment on cardiovascular
      mortality. MEASUREMENTS AND MAIN RESULTS: A total of 939 elderly were studied
      (median follow-up, 69 mo). Compared with the control group, the fully adjusted
      hazard ratios for cardiovascular mortality were 2.25 (confidence interval [CI],
      1.41 to 3.61) for the untreated severe OSA group, 0.93 (CI, 0.46 to 1.89) for the
      CPAP-treated group, and 1.38 (CI, 0.73 to 2.64) for the untreated mild to
      moderate OSA group. CONCLUSIONS: Severe OSA not treated with CPAP is associated
      with cardiovascular death in the elderly, and adequate CPAP treatment may reduce
      this risk.

PMID- 22983958
TI  - Disparities in access to lung transplantation for patients with cystic fibrosis
      by socioeconomic status.
AB  - RATIONALE: Although previous studies suggest that access to care for patients
      with cystic fibrosis (CF) does not vary appreciably by socioeconomic status
      (SES), disparities with respect to access to lung transplantation for patients
      with CF are largely unknown. OBJECTIVES: To determine whether access to lung
      transplantation for patients with CF differs according to SES. METHODS:
      Observational study involving 2,167 adult patients with CF from the CF Foundation
      Patient registry who underwent their first lung transplant evaluation between
      2001 and 2009. The primary outcome was acceptance for lung transplant after
      initial evaluation. The main SES indicator was Medicaid status. Alternate SES
      indicators included race, educational attainment, ZIP code-level median household
      income, and driving time from residence to closest lung transplant center.
      MEASUREMENTS AND MAIN RESULTS: The odds that Medicaid recipients were not
      accepted for lung transplant were 1.56-fold higher (95% confidence interval [CI],
      1.27-1.92) than patients without Medicaid, after multivariate adjustment for
      demographic characteristics, disease severity, and potential contraindications to
      lung transplant, and before or after use of the lung allocation score. This
      association was independent of other SES indicators, including race, educational
      attainment, ZIP code-level median household income, and driving time to closest
      transplant center (odds ratio [OR] = 1.37; 95% CI, 1.10-1.72). Patients not
      completing high school (OR = 2.37; 95% CI, 1.49-3.79) and those residing in the
      lowest (vs. highest) ZIP code median household income category (OR = 1.39; 95%
      CI, 1.01-1.93) also experienced a higher odds of not being accepted for lung
      transplant in multivariate analysis. CONCLUSIONS: In this nationally
      representative study of adult patients with CF, multiple indicators of low SES
      were associated with higher odds of not being accepted for lung transplant.

PMID- 22983959
TI  - Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary
      disease.
AB  - RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have
      evidence of systemic inflammation that may be implicated in the development of
      comorbidities. OBJECTIVES: To test the hypothesis that elevated levels of three
      inflammatory biomarkers are associated with increased risk of comorbidities in
      COPD. METHODS: We examined 8,656 patients with COPD from two large Danish
      population studies and during a median 5 years' follow-up recorded hospital
      admissions due to major comorbidities as endpoints. MEASUREMENTS AND MAIN
      RESULTS: We measured baseline C-reactive protein (CRP), fibrinogen, and leukocyte
      count, and recorded admissions due to ischemic heart disease, myocardial
      infarction, heart failure, type II diabetes, lung cancer, pneumonia, pulmonary
      embolism, hip fracture, and depression for all participants. Multifactorially
      adjusted risk of ischemic heart disease was increased by a factor of 2.19 (95%
      confidence interval, 1.48-3.23) in individuals with three biomarkers elevated
      (CRP > 3 mg/L, fibrinogen > 14 MUmol/L, and leukocyte count > 9 * 10(9)/L) versus
      individuals with all three biomarkers at or below these limits. Corresponding
      hazard ratios were 2.32 (1.34-4.04) for myocardial infarction, 2.63 (1.71-4.04)
      for heart failure, 3.54 (2.03-6.19) for diabetes, 4.00 (2.12-7.54) for lung
      cancer, and 2.71 (2.03-3.63) for pneumonia. There were no consistent differences
      in risk of pulmonary embolism, hip fracture, or depression as a function of these
      three biomarkers. CONCLUSIONS: Simultaneously elevated levels of CRP, fibrinogen,
      and leukocyte count are associated with a two- to fourfold increased risk of
      major comorbidities in COPD. These biomarkers may be an additional tool for
      clinicians to conduct stratified management of comorbidities in COPD.

PMID- 22983960
TI  - Caring for children with drug-resistant tuberculosis: practice-based
      recommendations.
AB  - The management of children with drug-resistant tuberculosis (DR-TB) is
      challenging, and it is likely that in many places, the roll-out of molecular
      diagnostic testing will lead to more children being diagnosed. There is a limited
      evidence base to guide optimal treatment and follow-up in the pediatric
      population; in existing DR-TB guidelines, the care of children is often relegated
      to small "special populations" sections. This article seeks to address this gap
      by providing clinicians with practical advice and guidance. This is achieved
      through review of the available literature on pediatric DR-TB, including research
      studies and international guidelines, combined with consensus opinion from a team
      of experts who have extensive experience in the care of children with DR-TB in a
      wide variety of contexts and with varying resources. The review covers treatment
      initiation, regimen design and treatment duration, management of comorbid
      conditions, treatment monitoring, adverse events, adherence promotion, and
      infection control, all within a multidisciplinary environment.

PMID- 22983961
TI  - Evidence that Cryptosporidium parvum populations are panmictic and unstructured
      in the Upper Midwest of the United States.
AB  - Cryptosporidium parvum is a zoonotic protozoan parasite that causes
      cryptosporidiosis, an infectious diarrheal disease primarily affecting humans and
      neonatal ruminants. Understanding the transmission dynamics of C. parvum,
      particularly the specific contributions of zoonotic and anthroponotic
      transmission, is critical to the control of this pathogen. This study used a
      population genetics approach to better understand the transmission of C. parvum
      in the Upper Midwest United States. A total of 254 C. parvum isolates from cases
      of human cryptosporidiosis in Minnesota and Wisconsin and diarrheic calves in
      Minnesota, Wisconsin, and North Dakota were genotyped at eight polymorphic loci.
      Isolates with a complete profile from all eight loci (n = 212) were used to
      derive a multilocus genotype (MLT), which was used in population genetic
      analyses. Among the 94 MLTs identified, 60 were represented by a single isolate.
      Approximately 20% of isolates belonged to MLT 2, a group that included both human
      and cattle isolates. Population analyses revealed a predominantly panmictic
      population with no apparent geographic or host substructuring.

PMID- 22983962
TI  - Germination and amplification of anthrax spores by soil-dwelling amoebas.
AB  - While anthrax is typically associated with bioterrorism, in many parts of the
      world the anthrax bacillus (Bacillus anthracis) is endemic in soils, where it
      causes sporadic disease in livestock. These soils are typically rich in organic
      matter and calcium that promote survival of resilient B. anthracis spores.
      Outbreaks of anthrax tend to occur in warm weather following rains that are
      believed to concentrate spores in low-lying areas where runoff collects. It has
      been concluded that elevated spore concentrations are not the result of
      vegetative growth as B. anthracis competes poorly against indigenous bacteria.
      Here, we test an alternative hypothesis in which amoebas, common in moist soils
      and pools of standing water, serve as amplifiers of B. anthracis spores by
      enabling germination and intracellular multiplication. Under simulated
      environmental conditions, we show that B. anthracis germinates and multiplies
      within Acanthamoeba castellanii. The growth kinetics of a fully virulent B.
      anthracis Ames strain (containing both the pX01 and pX02 virulence plasmids) and
      vaccine strain Sterne (containing only pX01) inoculated as spores in coculture
      with A. castellanii showed a nearly 50-fold increase in spore numbers after 72 h.
      In contrast, the plasmidless strain 9131 showed little growth, demonstrating that
      plasmid pX01 is essential for growth within A. castellanii. Electron and time
      lapse fluorescence microscopy revealed that spores germinate within amoebal
      phagosomes, vegetative bacilli undergo multiplication, and, following demise of
      the amoebas, bacilli sporulate in the extracellular milieu. This analysis
      supports our hypothesis that amoebas contribute to the persistence and
      amplification of B. anthracis in natural environments.

PMID- 22983963
TI  - Phylogenetically novel LuxI/LuxR-type quorum sensing systems isolated using a
      metagenomic approach.
AB  - A great deal of research has been done to understand bacterial cell-to-cell
      signaling systems, but there is still a large gap in our current knowledge
      because the majority of microorganisms in natural environments do not have
      cultivated representatives. Metagenomics is one approach to identify novel quorum
      sensing (QS) systems from uncultured bacteria in environmental samples. In this
      study, fosmid metagenomic libraries were constructed from a forest soil and an
      activated sludge from a coke plant, and the target genes were detected using a
      green fluorescent protein (GFP)-based Escherichia coli biosensor strain whose
      fluorescence was screened by spectrophotometry. DNA sequence analysis revealed
      two pairs of new LuxI family N-acyl-L-homoserine lactone (AHL) synthases and LuxR
      family transcriptional regulators (clones N16 and N52, designated AubI/AubR and
      AusI/AusR, respectively). AubI and AusI each produced an identical AHL, N
      dodecanoyl-L-homoserine lactone (C(12)-HSL), as determined by nuclear magnetic
      resonance (NMR) and mass spectrometry. Phylogenetic analysis based on amino acid
      sequences suggested that AusI/AusR was from an uncultured member of the
      Betaproteobacteria and AubI/AubR was very deeply branched from previously
      described LuxI/LuxR homologues in isolates of the Proteobacteria. The
      phylogenetic position of AubI/AubR indicates that they represent a QS system not
      acquired recently from the Proteobacteria by horizontal gene transfer but share a
      more ancient ancestry. We demonstrated that metagenomic screening is useful to
      provide further insight into the phylogenetic diversity of bacterial QS systems
      by describing two new LuxI/LuxR-type QS systems from uncultured bacteria.

PMID- 22983964
TI  - Quantification of bacterial indicators and zoonotic pathogens in dairy wastewater
      ponds.
AB  - Zoonotic pathogens in land-applied dairy wastewaters are a potential health risk.
      The occurrence and abundance of 10 pathogens and 3 fecal indicators were
      determined by quantitative real-time PCR (qPCR) in samples from 30 dairy
      wastewaters from southern Idaho. Samples tested positive for Campylobacter
      jejuni, stx(1)- and eaeA-positive Escherichia coli, Listeria monocytogenes,
      Mycobacterium avium subsp. paratuberculosis, and Salmonella enterica, with mean
      recoveries of genomic DNA corresponding to 10(2) to 10(4) cells ml(-1)
      wastewater. The most predominant organisms were C. jejuni and M. avium, being
      detected in samples from up to 21 and 29 of 30 wastewater ponds, respectively.
      The qPCR detection limits for the putative pathogens in the wastewaters ranged
      from 16 cells ml(-1) for M. avium to 1,689 oocysts ml(-1) for Cryptosporidium.
      Cryptosporidium and Giardia spp., Yersinia pseudotuberculosis, and pathogenic
      Leptospira spp. were not detected by qPCR.

PMID- 22983965
TI  - Novel method for enumeration of viable Lactobacillus plantarum WCFS1 cells after
      single-droplet drying.
AB  - Survival of probiotic bacteria during drying is not trivial. Survival percentages
      are very specific for each probiotic strain and can be improved by careful
      selection of drying conditions and proper drying carrier formulation. An
      experimental approach is presented, comprising a single-droplet drying method and
      a subsequent novel screening methodology, to assess the microbial viability
      within single particles. The drying method involves the drying of a single
      droplet deposited on a flat, hydrophobic surface under well-defined drying
      conditions and carrier formulations. Semidried or dried particles were subjected
      to rehydration, fluorescence staining, and live/dead enumeration using
      fluorescence microscopy. The novel screening methodology provided accurate
      survival percentages in line with conventional plating enumeration and was
      evaluated in single-droplet drying experiments with Lactobacillus plantarum WCFS1
      as a model probiotic strain. Parameters such as bulk air temperatures and the
      carrier matrices (glucose, trehalose, and maltodextrin DE 6) were varied.
      Following the experimental approach, the influence on the viability as a function
      of the drying history could be monitored. Finally, the applicability of the novel
      viability assessment was demonstrated for samples obtained from drying
      experiments at a larger scale.

PMID- 22983966
TI  - Sequential use of nitrogen compounds by Saccharomyces cerevisiae during wine
      fermentation: a model based on kinetic and regulation characteristics of nitrogen
      permeases.
AB  - The efficiency of nitrogen use is a key determinant of the completion of
      alcoholic fermentation. We analyzed the kinetics of consumption of 18 nitrogen
      compounds by 14 Saccharomyces cerevisiae strains of various origins in a
      synthetic medium that mimicked a grape must. The kinetic profiles of total
      nitrogen consumption were diverse, but the order of nitrogen source consumption
      was similar for all strains. The nitrogen compounds could be classified into
      three groups, according to their order of use: prematurely consumed (Lys), early
      consumed (Asp, Thr, Glu, Leu, His, Met, Ile, Ser, Gln, and Phe), and late
      consumed (ammonium, Val, Arg, Ala, Trp, and Tyr). The initial concentrations of
      these compounds did not alter the order in which they were consumed, except for
      arginine and ammonium. Early consumed amino acids are transported by specific
      permeases under Ssy1p-Ptr3p-Ssy5 (SPS)-mediated control that are expressed at the
      beginning of consumption. Most nitrogen compounds consumed late are transported
      by permeases under nitrogen catabolite repression (NCR), and others (Val, Trp,
      and Tyr) are transported by SPS-regulated low-affinity permeases. Therefore, the
      kinetic characteristics of transporters, as well as SPS and NCR, are likely key
      factors controlling the temporal sequence of consumption of nitrogen compounds
      and constitute a system highly conserved in S. cerevisiae species. This work
      sheds new light on the mechanistic basis of the sequential use of different
      nitrogen compounds in complex environments.

PMID- 22983967
TI  - Novel system for efficient isolation of Clostridium double-crossover allelic
      exchange mutants enabling markerless chromosomal gene deletions and DNA
      integration.
AB  - Isolation of Clostridium mutants based on gene replacement via allelic exchange
      remains a major limitation for this important genus. Use of a heterologous
      counterselection marker can facilitate the identification of the generally rare
      allelic exchange events. We report on the development of an inducible
      counterselection marker and describe its utility and broad potential in quickly
      and efficiently generating markerless DNA deletions and integrations at any
      genomic locus without the need for auxotrophic mutants or the use of the mobile
      group II introns. This system is based on a codon-optimized mazF toxin gene from
      Escherichia coli under the control of a lactose-inducible promoter from
      Clostridium perfringens. This system is potentially applicable to almost all
      members of the genus Clostridium due to their similarly low genomic GC content
      and comparable codon usage. We isolated all allelic-exchange-based gene deletions
      (ca_p0167, sigF, and sigK) or disruptions (ca_p0157 and sigF) we attempted and
      integrated a 3.6-kb heterologous DNA sequence (made up of a Clostridium
      ljungdahlii 2.1-kb formate dehydrogenase [fdh] gene plus a FLP recombination
      target [FRT]-flanked thiamphenicol resistance marker) into the Clostridium
      acetobutylicum chromosome. Furthermore, we report on the development of a plasmid
      system with inducible segregational instability, thus enabling efficient
      deployment of the FLP-FRT system to generate markerless deletion or integration
      mutants. This enabled expeditious deletion of the thiamphenicol resistance marker
      from the fdh integrant strain as well as the sigK deletion strain. More
      generally, our system can potentially be applied to other organisms with
      underdeveloped genetic tools.

PMID- 22983968
TI  - Prevalence and genetic diversity of Bartonella spp. in small mammals from
      Southeastern Asia.
AB  - Among 1,341 blood samples from rodents that were trapped in Southeast Asia
      between 2008 and 2010, we found a prevalence of Bartonella infection ranging from
      9.6 to 11.9%. Bartonella species identified (143 isolates) included B.
      elizabethae, B. coopersplainsensis, B. phoceensis, B. queenslandensis, B.
      rattimassiliensis, B. tribocorum, and three new putative Bartonella species.

PMID- 22983969
TI  - Annotation of the modular polyketide synthase and nonribosomal peptide synthetase
      gene clusters in the genome of Streptomyces tsukubaensis NRRL18488.
AB  - The high G+C content and large genome size make the sequencing and assembly of
      Streptomyces genomes more difficult than for other bacteria. Many
      pharmaceutically important natural products are synthesized by modular polyketide
      synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The analysis of
      such gene clusters is difficult if the genome sequence is not of the highest
      quality, because clusters can be distributed over several contigs, and sequencing
      errors can introduce apparent frameshifts into the large PKS and NRPS proteins.
      An additional problem is that the modular nature of the clusters results in the
      presence of imperfect repeats, which may cause assembly errors. The genome
      sequence of Streptomyces tsukubaensis NRRL18488 was scanned for potential PKS and
      NRPS modular clusters. A phylogenetic approach was used to identify multiple
      contigs belonging to the same cluster. Four PKS clusters and six NRPS clusters
      were identified. Contigs containing cluster sequences were analyzed in detail by
      using the ClustScan program, which suggested the order and orientation of the
      contigs. The sequencing of the appropriate PCR products confirmed the ordering
      and allowed the correction of apparent frameshifts resulting from sequencing
      errors. The product chemistry of such correctly assembled clusters could also be
      predicted. The analysis of one PKS cluster showed that it should produce a
      bafilomycin-like compound, and reverse transcription (RT)-PCR was used to show
      that the cluster was transcribed.

PMID- 22983970
TI  - Comparison of methods for evaluation of the bactericidal activity of copper
      sputtered surfaces against methicillin-resistant Staphylococcus aureus.
AB  - Bacteria can survive on hospital textiles and surfaces, from which they can be
      disseminated, representing a source of health care-associated infections (HCAIs).
      Surfaces containing copper (Cu), which is known for its bactericidal properties,
      could be an efficient way to lower the burden of potential pathogens. The
      antimicrobial activity of Cu-sputtered polyester surfaces, obtained by direct
      current magnetron sputtering (DCMS), against methicillin-resistant Staphylococcus
      aureus (MRSA) was tested. The Cu-polyester microstructure was characterized by
      high-resolution transmission electron microscopy to determine the microstructure
      of the Cu nanoparticles and by profilometry to assess the thickness of the
      layers. Sputtering at 300 mA for 160 s led to a Cu film thickness of 20 nm (100
      Cu layers) containing 0.209% (wt/wt) polyester. The viability of MRSA strain ATCC
      43300 on Cu-sputtered polyester was evaluated by four methods: (i) mechanical
      detachment, (ii) microcalorimetry, (iii) direct transfer onto plates, and (iv)
      stereomicroscopy. The low efficacy of mechanical detachment impeded bacterial
      viability estimations. Microcalorimetry provided only semiquantitative results.
      Direct transfer onto plates and stereomicroscopy seemed to be the most suitable
      methods to evaluate the bacterial inactivation potential of Cu-sputtered
      polyester surfaces, since they presented the least experimental bias. Cu
      polyester samples sputtered for 160 s by DCMS were further tested against 10
      clinical MRSA isolates and showed a high level of bactericidal activity, with a 4
      log(10) reduction in the initial MRSA load (10(6) CFU) within 1 h. Cu-sputtered
      polyester surfaces might be of use to prevent the transmission of HCAI pathogens.

PMID- 22983971
TI  - Modeling the growth of Listeria monocytogenes in soft blue-white cheese.
AB  - The aim of this study was to develop a predictive model simulating growth over
      time of the pathogenic bacterium Listeria monocytogenes in a soft blue-white
      cheese. The physicochemical properties in a matrix such as cheese are essential
      controlling factors influencing the growth of L. monocytogenes. We developed a
      predictive tertiary model of the bacterial growth of L. monocytogenes as a
      function of temperature, pH, NaCl, and lactic acid. We measured the variations
      over time of the physicochemical properties in the cheese. Our predictive model
      was developed based on broth data produced in previous studies. New growth data
      sets were produced to independently calibrate and validate the developed model. A
      characteristic of this tertiary model is that it handles dynamic growth
      conditions described in time series of temperature, pH, NaCl, and lactic acid.
      Supplying the model with realistic production and retail conditions showed that
      the number of L. monocytogenes cells increases 3 to 3.5 log within the shelf life
      of the cheese.

PMID- 22983972
TI  - Cross-site soil microbial communities under tillage regimes: fungistasis and
      microbial biomarkers.
AB  - The exploitation of soil ecosystem services by agricultural management strategies
      requires knowledge of microbial communities in different management regimes. Crop
      cover by no-till management protects the soil surface, reducing the risk of
      erosion and nutrient leaching, but might increase straw residue-borne and
      soilborne plant-pathogenic fungi. A cross-site study of soil microbial
      communities and Fusarium fungistasis was conducted on six long-term agricultural
      fields with no-till and moldboard-plowed treatments. Microbial communities were
      studied at the topsoil surface (0 to 5 cm) and bottom (10 to 20 cm) by general
      bacterial and actinobacterial terminal restriction fragment length polymorphism
      (T-RFLP) and phospholipid fatty acid (PLFA) analyses. Fusarium culmorum soil
      fungistasis describing soil receptivity to plant-pathogenic fungi was explored by
      using the surface layer method. Soil depth had a significant impact on general
      bacterial as well as actinobacterial communities and PLFA profiles in no-till
      treatment, with a clear spatial distinction of communities (P < 0.05), whereas
      the depth-related separation of microbial communities was not observed in plowed
      fields. The fungal biomass was higher in no-till surface soil than in plowed soil
      (P < 0.07). Soil total microbial biomass and fungal biomass correlated with
      fungistasis (P < 0.02 for the sum of PLFAs; P < 0.001 for PLFA 18:2omega6). Our
      cross-site study demonstrated that agricultural management strategies can have a
      major impact on soil microbial community structures, indicating that it is
      possible to influence the soil processes with management decisions. The
      interactions between plant-pathogenic fungi and soil microbial communities are
      multifaceted, and a high level of fungistasis could be linked to the high
      microbial biomass in soil but not to the specific management strategy.

PMID- 22983973
TI  - New insight into the ochratoxin A biosynthetic pathway through deletion of a
      nonribosomal peptide synthetase gene in Aspergillus carbonarius.
AB  - Ochratoxin A (OTA), a mycotoxin produced by Aspergillus and Penicillium species,
      is composed of a dihydroisocoumarin ring linked to phenylalanine, and its
      biosynthetic pathway has not yet been completely elucidated. Most of the
      knowledge regarding the genetic and enzymatic aspects of OTA biosynthesis has
      been elucidated in Penicillium species. In Aspergillus species, only pks genes
      involved in the initial steps of the pathway have been partially characterized.
      In our study, the inactivation of a gene encoding a nonribosomal peptide
      synthetase (NRPS) in OTA-producing A. carbonarius ITEM 5010 has eliminated the
      ability of this fungus to produce OTA. This is the first report on the
      involvement of an nrps gene product in OTA biosynthetic pathway in an Aspergillus
      species. The absence of OTA and ochratoxin alpha, the isocoumaric derivative of
      OTA, and the concomitant increase of ochratoxin beta, the dechloro analog of
      ochratoxin alpha, were observed in the liquid culture of transformed strain. The
      data provide the first evidence that the enzymatic step adding phenylalanine to
      polyketide dihydroisocoumarin precedes the chlorination step to form OTA in A.
      carbonarius and that ochratoxin alpha is a product of hydrolysis of OTA, giving
      an interesting new insight into the biosynthetic pathway of the toxin.

PMID- 22983974
TI  - Interaction of operational and physicochemical factors leading to Gordonia amarae
      like foaming in an incompletely nitrifying activated sludge plant.
AB  - The overgrowth of Gordonia amarae-like bacteria in the mixed liquor of an
      incompletely nitrifying water reclamation plant was inversely correlated with
      temperature (r = -0.78; P < 0.005) and positively correlated with the solids
      retention time (SRT) obtained a week prior to sampling (r = 0.67; P < 0.005).
      Drops followed by spikes in the food-to-mass ratio (0.18 to 0.52) and biochemical
      oxygen demand concentrations in primary effluent (94 to 298 mg liter(-1))
      occurred at the initiation of G. amarae-like bacterial growth. The total
      bacterial concentration did not increase as concentrations of G. amarae-like
      cells increased, but total bacterial cell concentrations fluctuated in a manner
      similar to that of G. amarae-like bacteria in the pseudo-steady state. The
      ammonium ion removal rate (percent) was inversely related to G. amarae-like cell
      concentrations during accelerated growth and washout phases. The dissolved oxygen
      concentration decreased as the G. amarae-like cell concentration decreased. The
      concentrations of G. amarae-like cells peaked (2.47 * 10(9) cells liter(-1))
      approximately 1.5 months prior to foaming. Foaming occurred during the late
      pseudo-steady-state phase, when temperature declines reversed. These findings
      suggested that temperature changes triggered operational and physicochemical
      changes favorable to the growth of G. amarae-like bacteria. Fine-scale
      quantitative PCR (qPCR) monitoring at weekly intervals allowed a better
      understanding of the factors affecting this organism and indicated that frequent
      sampling was required to obtain statistical significance with factors changing as
      the concentrations of this organism increased. Furthermore, the early
      identification of G. amarae-like cells when they are confined to mixed liquor
      (10(7) cells liter(-1)) allows management strategies to prevent foaming.

PMID- 22983975
TI  - Synergistic effects of high hydrostatic pressure, mild heating, and amino acids
      on germination and inactivation of Clostridium sporogenes spores.
AB  - The synergistic effects of high hydrostatic pressure (HHP), mild heating, and
      amino acids on the germination of Clostridium sporogenes spores were examined by
      determining the number of surviving spores that returned to vegetative growth
      after pasteurization following these treatments. Pressurization at 200 MPa at a
      temperature higher than 40 degrees C and treatment with some of the 19 l-amino
      acids at 10 mM or higher synergistically facilitated germination. When one of
      these factors was omitted, the level of germination was insignificant. Pressures
      of 100 and 400 MPa were less effective than 200 MPa. The spores were effectively
      inactivated by between 1.8 and 4.8 logs by pasteurization at 80 degrees C after
      pressurization at 200 MPa at 45 degrees C for 120 min with one of the amino acids
      with moderate hydrophobicity, such as Leu, Phe, Cys Met, Ala, Gly, or Ser.
      However, other amino acids showed poor inactivation effects of less than 0.9
      logs. Spores in solutions containing 80 mM of either Leu, Phe, Cys, Met, Ala,
      Gly, or Ser were successfully inactivated by pasteurization by more than 5.4 logs
      after pressurization at 200 MPa at 70 degrees C for 15 to 120 min. Ala and Met
      reduced the spore viability by 2.8 and 1.8 logs, respectively, by pasteurization
      at a concentration of 1 mM under 200 MPa at 70 degrees C. These results indicate
      that germination of the spores is facilitated by a combination of high
      hydrostatic pressure, mild heating, and amino acids.

PMID- 22983976
TI  - Risk of repeat visits, hospitalisation and death after uncompleted and completed
      visits to the emergency department: a prospective observation study.
AB  - OBJECTIVES: The needs of patients with uncompleted visits to the emergency
      department (ED) are uncertain. The aim was to evaluate ED patients who leave
      against medical advice (AMA) and who leave without being seen (WBS) regarding
      repeat ED visits, hospitalisation and mortality within 30 days. METHODS: The
      National University Hospital operates the only ED for adults in the capital area
      of Reykjavik. The source of data was the electronic records for patients 18 years
      or older, who left AMA, who left WBS, who had the ICD-10 code Z53.2, or who
      completed their visits. ED visits, hospital admissions and the death registry are
      filed with the personal identification number, which enabled recognition of the
      index visit, and the outcomes, rates of return visits, hospitalisation and death.
      RESULTS: Of 107 119 patients, 77 left AMA, 4471 left WBS and 423 had code Z53.2.
      The HR for returning to the ED within 30 days was 4.79 for AMA patients, 4.84 for
      WBS patients and 3.67 for Z53.2 patients. The HR for hospitalisation within 30
      days was 6.90 for AMA patients, 1.09 for WBS patients and 1.07 for Z53.2
      patients. The HR for death within 30 days was 10.97 for AMA patients, 0.84 for
      WBS and no deaths occurred among Z53.2 patients. DISCUSSION: During 30 days
      follow-up, AMA and WBS patients had an increased rate of repeat ED visits
      compared with those patients who completed their ED visits. AMA patients also had
      an increased rate of hospitalisations.

PMID- 22983977
TI  - Exploring variation in emergency bed use by older people.

PMID- 22983978
TI  - Effectiveness of a five-level Paediatric Triage System: an analysis of resource
      utilisation in the emergency department in Taiwan.
AB  - OBJECTIVES: To examine the effectiveness of a five-level Paediatric Triage and
      Acuity System (Ped-TTAS) by comparing the reliability of patient prioritisation
      and resource utilisation with the four-level Paediatric Taiwan Triage System (Ped
      TTS) among non-trauma paediatric patients in the emergency department (ED).
      METHODS: The study design used was a retrospective longitudinal analysis based on
      medical chart review and a computer database. Except for a shorter list of
      complaints and some abnormal vital sign criteria modifications, the structure and
      triage process for applying Ped-TTAS was similar to that of the Paediatric
      Canadian Emergency Triage and Acuity Scale. Non-trauma paediatric patients
      presenting to the ED were triaged by well-trained triage nurses using the four
      level Ped-TTS in 2008 and five-level Ped-TTAS in 2010. Hospitalisation rates and
      medical resource utilisation were analysed by acuity levels between the
      contrasting study groups. RESULTS: There was a significant difference in patient
      prioritisation between the four-level Ped-TTS and five-level Ped-TTAS. Improved
      differentiation was observed with the five-level Ped-TTAS in predicting
      hospitalisation rates and medical costs. CONCLUSIONS: The five-level Ped-TTAS is
      better able to discriminate paediatric patients by triage acuity in the ED and is
      also more precise in predicting resource utilisation. The introduction of a more
      accurate acuity and triage system for use in paediatric emergency care should
      provide greater patient safety and more timely utilisation of appropriate ED
      resources.

PMID- 22983979
TI  - Role of routine pelvic radiography in initial evaluation of stable, high-energy,
      blunt trauma patients.
AB  - BACKGROUND: Pelvic fractures are among the most devastating traumatic injuries
      accompanied by high morbidity and mortality rate leading to catastrophic outcomes
      and haemodynamic consequences. Although Advanced Trauma Life Support (ATLS)
      recommends performing pelvic radiography in all major blunt trauma patients,
      several lines of evidence recommend that it can be limited to those blunt trauma
      patients who are haemodynamically unstable or have positive pelvic physical
      examination. Thus, we performed this study in order to evaluate the efficacy of
      routine pelvic radiography in haemodynamically stable, high-energy, blunt trauma
      patients. METHODS: This was a prospective cross-sectional study including all the
      haemodynamically stable, high-energy, blunt trauma patients with negative pelvic
      physical examination referring to our trauma centre during a 5-month period (May
      September 2010). Pelvic radiographies were performed and reviewed for
      abnormalities. In those who had negative pelvic physical examination and the
      radiography was not revealing enough, CT imaging was requested and reviewed.
      RESULTS: During the study period, 1679 high-energy blunt trauma patients referred
      to our centre out of which 389 were haemodynamically stable and had negative
      pelvic physical examination. Pelvic radiography was found to be normal in all the
      patients except one (0.25%) who had pelvic fracture. Only three patients required
      CT imaging out of which two (0.5%) were found to be normal. CONCLUSIONS: Pelvic
      radiography could be eliminated from the primary survey protocol of the patients
      with high-energy blunt trauma who are haemodynamically stable and have negative
      pelvic physical examination.

PMID- 22983980
TI  - Avoidable emergency admissions?
AB  - BACKGROUND: Use of specialist healthcare services is increasing. AIM: To evaluate
      whether alternative healthcare services could reduce the need for admissions to
      specialist care hospitals. DESIGN: Prospective observational study of emergency
      referrals for admission to specialist care. SETTING: A single out-of-hours
      primary care centre (OPCC) in Norway. METHOD: Out-of-hours physicians registered
      their referrals for hospital admission and stated whether the admission could
      have been avoided given the availability of six other healthcare services.
      RESULTS: Of 1083 registered encounters at the OPCC, 152 (14%) were referred for
      specialist care hospital admission. According to the referring physician, 32
      (21%) of these referrals could have been avoided. The most eligible alternatives
      to such referrals were next-day appointments at a specialist outpatient clinic
      (11 of 32 referrals), or admission to a community hospital (21 of 32 referrals),
      or a nursing home (nine of 32 referrals). Respiratory (eight of 32 referrals) and
      gastrointestinal problems (12 of 32 referrals) were the most common among
      avoidable admissions. CONCLUSIONS: The use of specialist care hospital admission
      can be reduced if appropriate alternatives are available.

PMID- 22983981
TI  - Facial petechia as a sign of strangulation in trauma victims.

PMID- 22983982
TI  - Oral anticoagulation improves the prognosis of octogenarian patients with atrial
      fibrillation undergoing percutaneous coronary intervention and stenting.
AB  - BACKGROUND: a significant proportion of octogenarian patients with atrial
      fibrillation (AF) undergo percutaneous coronary intervention (PCI) with stenting.
      Dual antiplatelet therapy is recommended in these patients, requiring a period of
      triple therapy with dual antiplatelet agent plus oral anticoagulation (OAC).
      Concerns remain regarding the appropriateness of OAC in octogenarians. METHODS:
      we reviewed 604 patients (15.7% >=80 years) with AF undergoing PCI. Clinical
      follow-up was performed, recording any bleeding episode, thrombo-embolism and
      major adverse cardiac events (MACE = death, acute myocardial infarction and/or
      revascularisation of target lesion). We compared octogenarian patients in
      relation to treatment with OAC at discharge. A secondary aim was to compare
      octogenarian patients with non-octogenarian patients in terms of their clinical
      and demographic characteristics, management and clinical outcome. RESULTS: among
      the 604 patients, 95(15.7%) were aged >=80 years. Octogenarians had a higher
      median CHADS2 score (2.78 versus 2.01; P < 0.001) and HAS-BLED score (3.05 versus
      2.84; P = 0.028). After a follow-up of 17 +/- 14 months, all-cause death occurred
      in 33%, MACE in 44%, and major bleeding in 21%. OAC was associated with less MACE
      (28.9 versus 58.3%; P = 0.012) and a similar rate of major bleeding. On
      multivariable analysis, non-use of OAC at discharge was associated with increased
      MACE (OR = 4.3; 95% CI = 1.3-14.6; P = 0.02). CONCLUSION: octogenarian AF
      patients undergoing PCI/stenting have a high mortality rate and MACE, which can
      be reduced by means of OAC therapy.

PMID- 22983983
TI  - The indirect antioxidant sulforaphane protects against thiopurine-mediated
      photooxidative stress.
AB  - Long-term treatment with thiopurines, such as the widely used anticancer,
      immunosuppressive and anti-inflammatory agent azathioprine, combined with
      exposure to ultraviolet (UV) radiation is associated with increased oxidative
      stress, hyperphotosensitivity and high risk for development of aggressive
      squamous cell carcinomas of the skin. Sulforaphane, an isothiocyanate derived
      from broccoli, is a potent inducer of endogenous cellular defenses regulated by
      transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2),
      including cytoprotective enzymes and glutathione, which in turn act as efficient
      indirect and direct antioxidants that have long-lasting effects. Treatment with 6
      thioguanine, a surrogate for azathioprine, leads to profound sensitization to
      oxidative stress and glutathione depletion upon exposure to UVA radiation, the
      damaging effects of which are primarily mediated by generation of reactive oxygen
      species. The degree of sensitization is greater for irradiation exposures
      spanning the absorption spectrum of 6-thioguanine, and is dependent on the length
      of treatment and the level of guanine substitution with 6-thioguanine, suggesting
      that the 6-thioguanine that is incorporated in genomic DNA is largely responsible
      for this sensitization. Sulforaphane provides protection against UVA, but not
      UVB, radiation without affecting the levels of 6-thioguanine incorporation into
      DNA. The protective effect is lost under conditions of Nrf2 deficiency, implying
      that it is due to induction of Nrf2-dependent cytoprotective proteins, and that
      this strategy could provide protection against any potentially photosensitizing
      drugs that generate electrophilic or reactive oxygen species. Thus, our findings
      support the development of Nrf2 activators as protectors against drug-mediated
      photooxidative stress and encourage future clinical trials in populations at high
      risk for cutaneous photodamage and photocarcinogenesis.

PMID- 22983984
TI  - Downregulation of miR-144 is associated with colorectal cancer progression via
      activation of mTOR signaling pathway.
AB  - The mammalian target of rapamycin (mTOR) is a downstream integrator of essential
      pathways. mTOR signaling is frequently dysregulated in a variety of human
      cancers, and in silico analysis has revealed two miR-144 binding sites in the
      mTOR 3' untranslated region. We investigated the clinicopathologic magnitude of
      the mTOR pathway regulating microRNA, miR-144 in colorectal cancer (CRC) cases.
      The regulation of mTOR by miR-144 was examined with inhibitor miR-144-transfected
      cells. We also investigated changes in sensitivity to the mTOR inhibitor,
      rapamycin, in inhibitor miR-144-transfected cells. Quantitative RT-PCR was used
      to evaluate the clinicopathologic significance of miR-144 expression in 137 CRC.
      Furthermore, we assessed the correlation between CRC prognosis and the expression
      of 16 genes in the Akt/mTOR pathway. In vitro assays showed that mTOR is a direct
      target of miR-144, and downregulation of miR-144 facilitated proliferation of CRC
      cell line, HT29. In addition, the viability of HT29 cells with downregulated miR
      144 expression was significantly reduced with rapamycin treatment. Low expression
      levels of miR-144 were associated with enhanced malignant potential such as
      venous invasion (P = 0.0013), liver metastasis (P = 0.08), liver recurrence (P =
      0.0058) and poor prognosis (P = 0.0041). Multivariate analysis indicated that low
      miR-144 expression was an independent prognostic factor for survival. Among many
      genes consisting of the mTOR pathway, only high expression of Rictor was
      associated with poor prognosis of CRC. miR-144 is a meaningful prognostic marker.
      Downregulation of miR-144 leads to poor prognosis of CRC patients via activation
      of the mTOR signaling pathway.

PMID- 22983985
TI  - Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating
      expression of the let-7 and miR-200 microRNA family.
AB  - Colorectal cancer (CRC) is a complex disease with genetic and epigenetic
      alterations in many key oncogenes and tumor suppressor genes. The active
      principle of a gum resin from Boswellia serrata, 3-acetyl-11-keto-beta-boswellic
      acid (AKBA), has recently gained attention as a chemopreventive compound due to
      its ability to target key oncogenic proteins such as 5-lipoxygenase and nuclear
      factor-kappaB. AKBA has been shown to inhibit the growth of CRC cells; however,
      the precise molecular mechanisms underlying its anticancer activities in CRC
      remain unclear. We hypothesized that boswellic acids may achieve their
      chemopreventive effects by modulating specific microRNA (miRNA) pathways. We
      found that AKBA significantly up-regulated expression of the let-7 and miR-200
      families in various CRC cell lines. Both let-7 and miR-200 are putative tumor
      suppressive miRNAs. AKBA modulated the expression of several downstream targets
      of the let-7 and miR-200 families, such as CDK6, vimentin and E-cadherin. These
      data were further strengthened by miRNA knockdown studies, which revealed that
      inhibition of let-7i facilitated enhanced cancer cell proliferation, migration
      and invasion. In addition, AKBA also induced similar modulation of the let-7 and
      miR-200 downstream genes in CRC tumors orthotopically implanted in nude mice.
      These results indicate that AKBA-induced antitumor effects in CRC occur, at least
      partly through the up-regulation of specific miRNA pathways. Our data provide
      novel evidence that anticancer effects of boswellic acids are due in part to
      their ability to regulate cellular epigenetic machinery and further highlight the
      promise for this phytochemical in the preventative and therapeutic applications
      of CRC.

PMID- 22983986
TI  - The pmr gene, encoding a Ca2+-ATPase, is required for calcium and manganese
      homeostasis and normal development of hyphae and conidia in Neurospora crassa.
AB  - The pmr gene is predicted to encode a Ca(2+)-ATPase in the secretory pathway. We
      examined two strains of Neurospora crassa that lacked PMR: the Deltapmr strain,
      in which pmr was completely deleted, and pmr(RIP), in which the gene was
      extensively mutated. Both strains had identical, complex phenotypes. Compared to
      the wild type, these strains required high concentrations of calcium or manganese
      for optimal growth and had highly branched, slow-growing hyphae. They conidiated
      poorly, and the shape and size of the conidia were abnormal. Calcium accumulated
      in the Deltapmr strains to only 20% of the wild-type level. High concentrations
      of MnCl(2) (1 to 5 mM) in growth medium partially suppressed the morphological
      defects but did not alter the defect in calcium accumulation. The Deltapmr
      Deltanca-2 double mutant (nca-2 encodes a Ca(2+)-ATPase in the plasma membrane)
      accumulated 8-fold more calcium than the wild type, and the morphology of the
      hyphae was more similar to that of wild-type hyphae. Previous experiments failed
      to show a function for nca-1, which encodes a SERCA-type Ca(2+)-ATPase in the
      endoplasmic reticulum (B. J. Bowman, S. Abreu, E. Margolles-Clark, M. Draskovic,
      and E. J. Bowman, Eukaryot. Cell 10:654-661, 2011). The pmr(RIP) Deltanca-1
      double mutant accumulated small amounts of calcium, like the Deltapmr strain, but
      exhibited even more extreme morphological defects. Thus, PMR can apparently
      replace NCA-1 in the endoplasmic reticulum, but NCA-1 cannot replace PMR. The
      morphological defects in the Deltapmr strain are likely caused, in part, by
      insufficient concentrations of calcium and manganese in the Golgi compartment;
      however, PMR is also needed to accumulate normal levels of calcium in the whole
      cell.

PMID- 22983987
TI  - Stable transfection of the diplomonad parasite Spironucleus salmonicida.
AB  - Eukaryotic microbes are highly diverse, and many lineages remain poorly studied.
      One such lineage, the diplomonads, a group of binucleate heterotrophic
      flagellates, has been studied mainly due to the impact of Giardia intestinalis,
      an intestinal, diarrhea-causing parasite in humans and animals. Here we describe
      the development of a stable transfection system for use in Spironucleus
      salmonicida, a diplomonad that causes systemic spironucleosis in salmonid fish.
      We designed vectors in cassette format carrying epitope tags for localization
      (3*HA [where HA is hemagglutinin], 2* Escherichia coli OmpF linker and mouse
      langerin fusion sequence [2*OLLAS], 3*MYC) and purification of proteins (2* Strep
      Tag II-FLAG tandem-affinity purification tag or streptavidin binding peptide
      glutathione S-transferase [SBP-GST]) under the control of native or constitutive
      promoters. Three selectable gene markers, puromycin acetyltransferase (pac),
      blasticidin S-deaminase (bsr), and neomycin phosphotransferase (nptII), were
      successfully applied for the generation of stable transfectants. Site-specific
      integration on the S. salmonicida chromosome was shown to be possible using the
      bsr resistance gene. We epitope tagged six proteins and confirmed their
      expression by Western blotting. Next, we demonstrated the utility of these
      vectors by recording the subcellular localizations of the six proteins by laser
      scanning confocal microscopy. Finally, we described the creation of an S.
      salmonicida double transfectant suitable for colocalization studies. The
      transfection system described herein and the imminent completion of the S.
      salmonicida genome will make it possible to use comparative genomics as an
      investigative tool to explore specific, as well as general, diplomonad traits,
      benefiting research on both Giardia and Spironucleus.

PMID- 22983990
TI  - Evolutionary aspects of animal models.

PMID- 22983991
TI  - "Autopsy".

PMID- 22983988
TI  - Effects of carvedilol on heart failure with preserved ejection fraction: the
      Japanese Diastolic Heart Failure Study (J-DHF).
AB  - AIMS: The therapeutic strategy for heart failure with preserved ejection fraction
      (HFPEF) has not been established. The Japanese Diastolic Heart Failure Study (J
      DHF) is a multicentre, prospective, randomized, open, blinded-endpoint trial,
      designed to assess the effects of carvedilol in HFPEF patients. METHODS AND
      RESULTS: A total of 245 patients with heart failure and ejection fraction >40%
      were randomly assigned into those treated with (carvedilol group, n = 120) and
      without carvedilol (control group, n = 125). The primary outcome is a composite
      of cardiovascular death and unplanned hospitalization for heart failure. During a
      median follow-up of 3.2 years, the primary endpoint occurred in 29 patients in
      the carvedilol group and in 34 patients in the control group [adjusted hazard
      ratio (HR) 0.902, 95% confidence interval (CI) 0.546-1.488, P = 0.6854]. Another
      major composite endpoint, cardiovascular death and unplanned hospitalization for
      any cardiovascular causes, occurred in 38 patients of the carvedilol group and 52
      patients of the control group (HR 0.768, 95% CI 0.504-1.169; P = 0.2178). The
      target dose of carvedilol was 20 mg/day, but the median prescribed dose was 7.5
      mg/day. In the patients treated with standard doses (carvedilol >7.5 mg/day, n =
      58), this composite outcome was significantly less than in the controls (HR
      0.539, 95% CI 0.303-0.959; P = 0.0356), whereas it was comparable with the
      controls in the patients treated with carvedilol <=7.5 mg/day (n = 62, HR 1.070,
      95% CI 0.650-1.763; P = 0.7893). CONCLUSIONS: Carvedilol did not improve
      prognosis of HFPEF patients overall; however, the standard dose, not the low
      dose, prescription might be effective. This may facilitate further investigation.
      UMIN number: C000000318.

PMID- 22983992
TI  - Pathologic lesions?

PMID- 22983994
TI  - Endovascular retrieval of an embolized pacing electrode from a pulmonary artery
      following device extraction.

PMID- 22983995
TI  - Long-range correlations in motor unit discharge times at low forces are modulated
      by visual gain and age.
AB  - The purpose of this investigation was to examine the association between visual
      information and the size and temporal structure of the variability in index
      finger force and motor unit discharge times when young and old adults performed
      isometric contractions with a hand muscle. Single motor units (n = 32) in the
      first dorsal interosseus muscle were recorded as subjects [16 young (18-35 years
      old) and 16 old (>= 70 years old)] exerted a constant abduction force with the
      index finger during 60 s isometric contractions. The target force was displayed
      on a monitor in front of the subjects, and they were asked to match the index
      finger force to a target force. The amount of visual feedback, or gain of the
      signal, was varied between 24 (low gain) and 1175 pixels N(-1) (high gain). In
      addition, some trials were performed in the absence of visual feedback. The
      dependent variables were the variability (standard deviation and coefficient of
      variation) and the regularity (detrended fluctuation analysis self-similarity
      parameter, alpha) of motor unit discharge times and the abduction force. Motor
      unit discharge times became less regular with an increase in visual feedback gain
      for both young and old adults, whereas motor unit discharge variability was not
      influenced by changes in visual gain. The regularity of motor unit discharge
      times was less for old adults than for young adults, but the variability was
      greater for old adults. However, there was a significant association between the
      regularity of motor unit discharge times and the regularity of force for the old
      adults, but not the young adults. These observations suggest that adjustments in
      the synaptic inputs delivered to motor neurons with changes in the visual gain
      differed for young and old adults.

PMID- 22983996
TI  - Investigating cardiac energetics in heart failure.
AB  - The energetic requirements of the heart are, weight for weight, higher than for
      any other organ. The heart provides non-stop function for a lifetime, while
      maintaining energy in reserve in order to respond to increased demand. This
      demand is met by continuously recycling a relatively small pool of ATP, with the
      creatine kinase (CK) system acting as a spatial and temporal buffer. In the
      failing heart, key components of this system are downregulated, but whether these
      energetic changes are biomarkers or drivers of dysfunction and whether they
      represent therapeutic targets are the subjects of ongoing research. Key
      methodologies are now becoming available in vivo to help address these questions
      in mouse models, such as (31)P magnetic resonance spectroscopy to detect high
      energy phosphates and (1)H magnetic resonance spectroscopy to detect total
      creatine. This report briefly discusses the challenges involved in using these
      technologies, the application and pitfalls of murine surgical models of heart
      failure, and how this has contributed to our understanding of pathophysiology in
      recent years.

PMID- 22983997
TI  - Intestinal necrosis in young patient due to arterial tumour embolism.
AB  - A patient in the thirties, currently undergoing chemotherapy for metastatic
      osteosarcoma diagnosed 3 years earlier, was admitted with in the emergency
      department with abdominal pain. Laparoscopic surgery revealed severe inflammation
      and an abscess. 18 cm of small intestine was removed because of intestinal
      necrosis. Histological examination showed several arterial tumour emboli,
      morphologically similar to the primary sarcoma. The patient died 1 year after
      successful surgery. Because of the improved survival of patients with
      osteosarcoma, acute mesenteric ischaemia should be considered in acute abdomen in
      these patients.

PMID- 22983998
TI  - Epstein-Barr virus acute cholecystitis.

PMID- 22983999
TI  - A challenging case of epigastric pain: diagnosis and mini-invasive treatment of a
      large gastroduodenal artery pseudoaneurysm.
AB  - The authors present a case of a gastroduodenal artery pseudoaneurysm in a patient
      with a medical history of pancreatic surgery. The lesion was found and evaluated
      by ultrasound, CT-angiography and then treated with trans-catheter embolisation.
      This mini-invasive approach led to a complete resolution of the lesion.

PMID- 22984000
TI  - Appendicitis and uterine abscess: presentation of an unusual fistula between the
      gynaecological and gastrointestinal tracts.
AB  - The authors present the case of a 65-year-old woman with clinical and
      radiological evidence of pelvic sepsis and a medical history of endometrial
      ablation 20 years previously. She underwent laparotomy after failing to settle
      with a course of intravenous antibiotics and her appendix was found to have
      perforated into the uterus with abscess formation which had not discharged
      vaginally presumably due to widespread intrauterine synechia following her
      endometrial ablation. She underwent appendectomy and hysterectomy and made a full
      recovery with no complications. Macroscopic and microscopic examination suggested
      the appearances are those of an abscess of the uterine fundus with part of the
      appendix incorporating into the abscess mass.

PMID- 22984001
TI  - Dietzia species pacemaker pocket infection: an unusual organism in human
      infections.
AB  - An 87-year-old man presented 10 months following permanent pacemaker insertion
      with cellulitis-like inflammation around the impulse generator. Symptoms improved
      with oral flucloxacillin, but only days after stopping, the infection recurred,
      and he was admitted from clinic for intravenous antibiotics. Suspecting the
      source was likely Staphylococcal, intravenous flucloxacillin was started, and the
      patient's inflammatory markers responded adequately. Two samples of fluid were
      aspirated from the pacemaker site. These showed no bacterial growth using routine
      microbiological culture techniques. The samples were sent for 16S rDNA PCR and
      Dietzia species was detected in both samples. Dietzia species is an Actinomyces
      like organism, which is not commonly associated with human infection, but is
      reported to have been isolated from clinical specimens and thus presumptively
      associated with human disease. The pacemaker was explanted and the pocket
      debrided with no complications. He made a full recovery after a prolonged course
      of flucloxacillin.

PMID- 22984002
TI  - Gallbladder agenesis with midgut malrotation.
AB  - A 28-year-old female presented with a 4 year history of intermittent right upper
      quadrant pain. Clinical examination and ultrasound suggested a diagnosis of
      cholelithiasis and the patient was eventually booked for a laparoscopic
      cholecystectomy. Intraoperatively the patient was found to have gallbladder
      agenesis and small bowel malrotation with the duodenojejunal flexure to right of
      midline. The gallbladder fossa was filled with fibrous tissue. Both gallbladder
      agenesis and midgut malrotation are rare congenital abnormalities. Gallbladder
      agenesis has a similar presentation to more common gallbladder pathologies, such
      as cholecystitis. This case illustrates the limitations of and our over reliance
      on radiological imaging. Moreover, it highlights the need to have a high index
      suspicion of gallbladder agenesis when ultrasound is inconclusive. Further
      investigations and imaging with modalities such as MRI should be used to reduce
      the risks associated with unnecessary surgical intervention.

PMID- 22984003
TI  - A thrombus of the right upper pulmonary vein: detection by the use of a 64-MDCT.
AB  - Stroke is an important disease, because it is usually devastating and often
      fatal. Left atrial appendage (LAA) thrombi are well known as a cause for cerebral
      infarction, but pulmonary vein thrombi remain unknown. To detect LAA thrombi,
      transoesophageal echocardiography (TOE) is usually used. More recently, a 64
      slice multidetector CT (64-MDCT) has proved to be an option for identifying them.
      The patient was 77-year-old male, and had a lacuna infarction in pons. A 64-MDCT
      demonstrated a 3 to 4 mm thrombus at the proximal side of right upper pulmonary
      vein. After 2 months warfarin therapy, the thrombus disappeared. When assessing
      the possible cause for cerebral infarction, it is important to identify thrombi
      within the LAA, and in the left pulmonary vein. 64-MDCT seems to be more suitable
      and reliable than TOE to detect thrombi of the pulmonary vein, because of no
      influence of pulmonary air.

PMID- 22984004
TI  - Recent progress on type II diacylglycerol kinases: the physiological functions of
      diacylglycerol kinase delta, eta and kappa and their involvement in disease.
AB  - Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DAG) to produce
      phosphatidic acid (PA) and plays an important role in signal transduction by
      modulating the balance between these signalling lipids. To date, 10 mammalian DGK
      isozymes have been identified, and these isozymes are subdivided into five groups
      according to their structural features. The type II DGKs, consisting of delta1,
      delta2, eta1, eta2 and kappa isoforms, possess a pleckstrin homology (PH) domain
      at their N-termini in addition to the separate catalytic region. Moreover, DGKs
      delta1, delta2 and eta2 have a sterile alpha motif domain at their C-termini.
      Recent studies have revealed that type II DGKs play pivotal roles in a wide
      variety of mammalian signal transduction pathways for cell proliferation and
      differentiation and glucose metabolism and that the DGKs are involved in cancer,
      type II diabetes, seizures, hypospadias and bipolar disorder. This review
      summarizes the current knowledge on the properties and physiological functions of
      type II DGKs and their involvement in disease.

PMID- 22984005
TI  - Very long-chain fatty acids: elongation, physiology and related disorders.
AB  - Very long-chain fatty acids (VLCFAs) are fatty acids (FAs) with a chain-length of
      >=22 carbons. Mammals have a variety of VLCFAs differing in chain-length and the
      number of double bonds. Each VLCFA exhibits certain functions, for example in
      skin barrier formation, liver homeostasis, myelin maintenance, spermatogenesis,
      retinal function and anti-inflammation. These functions are elicited not by free
      VLCFAs themselves, but through their influences as components of membrane lipids
      (sphingolipids and glycerophospholipids) or precursors of inflammation-resolving
      lipid mediators. VLCFAs are synthesized by endoplasmic reticulum membrane
      embedded enzymes through a four-step cycle. The most important enzymes
      determining the tissue distribution of VLCFAs are FA elongases, which catalyze
      the first, rate-limiting step of the FA elongation cycle. Mammals have seven
      elongases (ELOVL1-7), each exhibiting a characteristic substrate specificity.
      Several inherited disorders are caused by mutations in genes involved in VLCFA
      synthesis or degradation. In this review, I describe the molecular mechanism of
      FA elongation and the responsible enzymes in mammals and yeast, as well as VLCFA
      related disorders in human.

PMID- 22984006
TI  - Conjugate eye deviation in acute intracerebral hemorrhage: stroke acute
      management with urgent risk-factor assessment and improvement--ICH (SAMURAI-ICH)
      study.
AB  - BACKGROUND AND PURPOSE: Conjugate eye deviation (CED) occurs frequently in
      patients with acute stroke. The purpose of this study was to elucidate the
      factors that correlate with CED as well as the relationship between CED and
      outcomes in patients with acute intracerebral hemorrhage. METHODS: A total of 211
      patients with acute supratentorial intracerebral hemorrhage were recruited in a
      multicenter, prospective study. CED was assessed with a National Institutes of
      Health Stroke Scale "best gaze" subscore of >=1. Hematoma location and volume
      were assessed on CT. RESULTS: Forty-five percent of the patients had CED. On
      multivariable analysis, right-sided lesion (OR, 2.36; 95% CI, 1.18-4.93),
      hematoma volume (OR, 1.07; 95% CI, 1.04-1.10 per 1 mL), and baseline Glasgow Coma
      Scale score (OR, 0.66; 95% CI, 0.53-0.80 per 1 point) were independently
      associated with CED. After adjusting for sex, age, intraventricular extension of
      the hematoma, baseline Glasgow Coma Scale score, and hematoma volume, the
      presence of CED both on admission and 72 hours later was an independent predictor
      of death or dependency at 3 months poststroke (OR, 5.77; 95% CI, 2.27-16.94). The
      optimal cutoff volume of hematoma related to CED was >=13.5 mL for patients with
      putaminal hemorrhage (sensitivity, 76%; specificity, 72%) and >=7.7 mL for
      patients with thalamic hemorrhage (sensitivity, 82%; specificity, 83%).
      CONCLUSIONS: The persistence of CED was a significant predictor of death or
      dependency after acute supratentorial intracerebral hemorrhage even after
      adjusting for initial severity and hematoma volume. CED can be evoked by a
      relatively smaller thalamic hematoma than a putaminal hematoma.

PMID- 22984007
TI  - CT interpretation in a telestroke network: agreement among a spoke radiologist,
      hub vascular neurologist, and hub neuroradiologist.
AB  - BACKGROUND AND PURPOSE: The American Stroke Association guidelines emphasized the
      need for further high-quality studies that assess agreement by radiologists and
      nonradiologists engaged in emergency telestroke assessments and decision-making.
      Therefore, the objective of this study was to determine the level of agreement of
      baseline brain CT scan interpretations of patients with acute stroke presenting
      to telestroke spoke hospitals between central reading committee neuroradiologists
      and each of 2 groups, spoke hospital radiologists and hub hospital vascular
      neurologists (telestrokologists). METHODS: The Stroke Team Remote Evaluation
      Using a Digital Observation Camera Arizona trial was a prospective, urban single
      hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site
      independent, audiovisual telemedicine and teleradiology system designed for
      remote evaluation of adult patients with acute stroke versus telephone
      consultation to assess eligibility for treatment with intravenous thrombolysis.
      In the telemedicine arm, the subjects' CT scans were interpreted by the hub
      telestrokologist and in the telephone arm by the spoke radiologist. All subjects'
      CT scans were subsequently interpreted centrally, independently, and blindly by 2
      hub neuroradiologists. The primary CT outcome was determination of a CT-based
      contraindication to thrombolytic treatment. Kappa statistics and exact agreement
      rates were used to analyze interobserver agreement. RESULTS: Fifty-four subjects
      underwent random assignment. The overall agreement for the presence of
      radiological contraindications to thrombolysis was excellent (0.91) and did not
      differ substantially between the hub telestrokologist to neuroradiologist and
      spoke radiologist to neuroradiologist (0.92 and 0.89, respectively). CONCLUSIONS:
      In the context of a telestroke network designed to assess patients with acute
      stroke syndromes, agreement over the presence or absence of radiological
      contraindications to thrombolysis was excellent whether the comparisons were
      between a telestrokologist and neuroradiologist or between spoke radiologist and
      neuroradiologist. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00623350.

PMID- 22984009
TI  - Higher stroke unit volume associated with improved quality of early stroke care
      and reduced length of stay.
AB  - BACKGROUND AND PURPOSE: Specialized stroke unit care improves outcome among
      patients with stroke, but it is unclear whether there are any scale advantages in
      costs and clinical outcome from treating a larger number of patients. We examined
      whether the case volume in stroke units was associated with quality of early
      stroke care, mortality, and hospital bed-day use. METHODS: In a nationwide
      population-based cohort study, we identified 63 995 patients admitted to stroke
      units in Denmark between 2003 and 2009. Data on exposure, outcome, and covariates
      were collected prospectively. Comparisons were clustered within stroke units and
      adjusted for patient and hospital characteristics. RESULTS: Patients in high
      volume stroke units overall had a better prognostic profile than patients in low
      volume stroke units. Patients in high-volume stroke units also received more
      processes of care in the early phase of stroke compared with patients in low
      volume stroke units (unadjusted difference, 9.84 percentage points; 95% CI, 3.98
      15.70). High stroke unit volume was associated with shorter length of the initial
      hospital stay (adjusted ratio, 0.49; 95% CI, 0.41-0.59) and reduced bed-day use
      in the first year after stroke (adjusted ratio, 0.79; 95% CI, 0.70-0.87). No
      association between volume and mortality was found. CONCLUSIONS: Patients
      admitted to high-volume stroke units received a higher quality of early stroke
      care and spent fewer days in the hospital compared with patients in low-volume
      units. We observed no association between volume and mortality.

PMID- 22984008
TI  - Detailed analysis of periprocedural strokes in patients undergoing intracranial
      stenting in Stenting and Aggressive Medical Management for Preventing Recurrent
      Stroke in Intracranial Stenosis (SAMMPRIS).
AB  - BACKGROUND AND PURPOSE: Enrollment in the Stenting and Aggressive Medical
      Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS)
      trial was halted due to the high risk of stroke or death within 30 days of
      enrollment in the percutaneous transluminal angioplasty and stenting arm relative
      to the medical arm. This analysis focuses on the patient and procedural factors
      that may have been associated with periprocedural cerebrovascular events in the
      trial. METHODS: Bivariate and multivariate analyses were performed to evaluate
      whether patient and procedural variables were associated with cerebral ischemic
      or hemorrhagic events occurring within 30 days of enrollment (termed
      periprocedural) in the percutaneous transluminal angioplasty and stenting arm.
      RESULTS: Of 224 patients randomized to percutaneous transluminal angioplasty and
      stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of
      these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had
      ischemic stroke, and 2 had cerebral infarcts with temporary signs within the
      periprocedural period. Ischemic events were categorized as perforator occlusions
      (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion
      (2). Multivariate analyses showed that higher percent stenosis, lower modified
      Rankin score, and clopidogrel load associated with an activated clotting time
      above the target range were associated (P <= 0.05) with hemorrhagic stroke.
      Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P
      <= 0.05) with ischemic events. CONCLUSIONS: Periprocedural strokes in SAMMPRIS
      had multiple causes with the most common being perforator occlusion. Although
      risk factors for periprocedural strokes could be identified, excluding patients
      with these features from undergoing percutaneous transluminal angioplasty and
      stenting to lower the procedural risk would limit percutaneous transluminal
      angioplasty and stenting to a small subset of patients. Moreover, given the small
      number of events, the present data should be used for hypothesis generation
      rather than to guide patient selection in clinical practice. Clinical Trial
      Registration Information- URL: http://clinicaltrials.gov. Unique Identifier:
      NCT00576693.

PMID- 22984010
TI  - Associations among vascular risk factors, carotid atherosclerosis, and cortical
      volume and thickness in older adults.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate whether the
      Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness
      are associated with cortical volume and thickness. METHODS: Consecutive subjects
      participating in a prospective cohort study of aging and mild cognitive
      impairment enriched for vascular risk factors for atherosclerosis underwent
      structural MRI scans at 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was
      used to obtain regional measures of neocortical volumes (mm3) and thickness (mm).
      Multiple linear regression was used to determine the association of Framingham
      Cardiovascular Risk Profile and carotid artery intima-media thickness with
      cortical volume and thickness. RESULTS: One hundred fifty-two subjects (82 men)
      were aged 78 (+/-7) years, 94 had a clinical dementia rating of 0, 58 had a
      clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was
      28+/-2. Framingham Cardiovascular Risk Profile score was inversely associated
      with total gray matter volume and parietal and temporal gray matter volume
      (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely
      associated with parietal and total cerebral gray matter thickness (adjusted
      P<0.03). Carotid artery intima-media thickness was inversely associated with
      thickness of parietal gray matter only (adjusted P=0.04). Including history of
      myocardial infarction or stroke and radiological evidence of brain infarction, or
      apolipoprotein E genotype did not alter relationships with Framingham
      Cardiovascular Risk Profile or carotid artery intima-media thickness.
      CONCLUSIONS: Increased cardiovascular risk was associated with reduced gray
      matter volume and thickness in regions also affected by Alzheimer disease
      independent of infarcts and apolipoprotein E genotype. These results suggest a
      "double hit" toward developing dementia when someone with incipient Alzheimer
      disease also has high cardiovascular risk.

PMID- 22984011
TI  - Mutant erythropoietin without erythropoietic activity is neuroprotective against
      ischemic brain injury.
AB  - BACKGROUND AND PURPOSE: Erythropoietin (EPO) confers potent neuroprotection
      against ischemic injury. However, treatment for stroke requires high doses and
      multiple administrations of EPO, which may cause deleterious side effects due to
      its erythropoietic activity. This study identifies a novel nonerythropoietic
      mutant EPO and investigates its potential neuroprotective effects and underlying
      mechanism in an animal model of cerebral ischemia. METHODS: We constructed a
      series of mutant EPOs, each containing a single amino acid mutation within the
      erythropoietic motif, and tested their erythropoietic activity. Using cortical
      neuronal cultures exposed to N-methyl-d-aspartate neurotoxicity and a murine
      model of transient middle cerebral artery occlusion, neuroprotection and
      neurofunctional outcomes were assessed as well as activation of intracellular
      signaling pathways. RESULTS: The serine to isoleucine mutation at position 104
      (S104I-EPO) completely abolished the erythropoietic and platelet-stimulating
      activity of EPO. Administration of S104I-EPO significantly inhibited N-methyl-d
      aspartate-induced neuronal death in primary cultures and protected against
      cerebral infarction and neurological deficits with an efficacy similar to that of
      wild-type EPO. Both S104-I-EPO and wild-type EPO activated similar prosurvival
      signaling pathways such as phosphatidylinositol 3-kinase/AKT, mitogen-activated
      protein kinase/extracellular signal-regulated kinase 1/2, and STAT5. Inhibition
      of phosphatidylinositol 3-kinase/AKT or mitogen-activated protein
      kinase/extracellular signal-regulated kinase 1/2 signaling pathways significantly
      attenuated the neuroprotective effects of S104-I-EPO, indicating that activation
      of these pathways underlies the neuroprotective mechanism of mutant EPO against
      cerebral ischemia. CONCLUSIONS: S104-I-EPO confers neuroprotective effects
      comparable to those of wild-type EPO against ischemic brain injury with the added
      benefit of lacking erythropoietic and platelet-stimulating side effects. Our
      novel findings suggest that the nonerythropoietic mutant EPO is a legitimate
      candidate for ischemic stroke intervention.

PMID- 22984012
TI  - Poststroke spasticity management.

PMID- 22984013
TI  - What causes disability after transient ischemic attack and minor stroke?: Results
      from the CT and MRI in the Triage of TIA and minor Cerebrovascular Events to
      Identify High Risk Patients (CATCH) Study.
AB  - BACKGROUND AND PURPOSE: Minor stroke and transient ischemic attack portend a
      significant risk of disability. Three possible mechanisms for this include
      disability not captured by the National Institutes of Health Stroke Scale,
      symptom progression, or recurrent stroke. We sought to assess the relative impact
      of these mechanisms on disability in a population of patients with transient
      ischemic attack and minor stroke. METHODS: Five hundred ten consecutive minor
      stroke (National Institutes of Health Stroke Scale<4) or patients with transient
      ischemic attack who were previously not disabled and had a CT/CT angiography
      completed within 24 hours of symptom onset were prospectively enrolled.
      Disability was assessed at 90 days using the modified Rankin Scale. Predictors of
      disability (modified Rankin Scale>=2) and the relative impact of the initial
      event versus recurrent events were assessed. RESULTS: Seventy-four of 499 (15%;
      95% CI, 12%-18%) patients had a disabled outcome. Baseline factors predicting
      disability were: age>=60 years, diabetes mellitus, premorbid modified Rankin
      Scale 1, ongoing symptoms, baseline National Institutes of Health Stroke Scale,
      CT/CT angiography-positive metric, and diffusion-weighted imaging positivity. In
      the multivariable analysis ongoing symptoms (OR, 2.4; 95% CI, 1.3-4.4; P=0.004),
      diabetes mellitus (OR, 2.3; 95% CI, 1.2-4.3; P=0.009), female sex (OR, 1.8; 95%
      CI, 1.1-3; P=0.025), and CT/CT angiography-positive metric (OR, 2.4; 95% CI, 1.4
      4; P=0.001) predicted disability. Of the 463 patients who did not have a
      recurrent event, 55 were disabled (12%). By contrast 19 of 36 (53%) patients were
      disabled after a recurrent event (risk ratio, 4.4; 95% CI, 3-6.6; P<0.0001).
      CONCLUSIONS: We found that a substantial proportion of patients with transient
      ischemic attack and minor stroke become disabled. In terms of absolute numbers,
      most patients have disability as a result of their presenting event; however,
      recurrent events have the largest relative impact on outcome.

PMID- 22984014
TI  - The spectroscopist's lament.

PMID- 22984015
TI  - Letter by Yeo et al regarding article, "Time-dependent test characteristics of
      head CT in patients suspected of nontraumatic subarachnoid hemorrhage".

PMID- 22984016
TI  - Monash transient ischemic attack triaging treatment: safety of a transient
      ischemic attack mechanism-based outpatient model of care.
AB  - BACKGROUND AND PURPOSE: Controversy surrounds the need for routine hospital
      admission for transient ischemic attack. The Monash Transient Ischemic Attack
      Triaging Treatment (M3T) model adopts rapid management in the emergency
      department followed by outpatient management prioritized by stroke mechanism. We
      compared safety and processes of care between M3T and the previous model of
      routine admission. METHODS: Study cohorts consisted of patients managed with M3T
      (2004-2007) and the previous model (2003-2004). We determined 90-day stroke
      outcome using clinical and medical record review and data linkage to the
      population level state-wide hospital discharge morbidity database. We compared
      models of care using risk difference analysis, followed by logistic regression to
      adjust for previous indicators of risk. Secondary outcomes were proportions
      admitted, proportions undergoing carotid ultrasound, times to ultrasound and
      revascularization, and medication prescription. RESULTS: In M3T (mean age, 64.7+/
      14.7) 85/488 (17.4%) patients were admitted compared with 117/169 (62.9%) in the
      previous model (mean age, 72.5+/-13.9). With near-complete follow-up, 90-day
      stroke outcome was 1.50% (95% confidence interval, 0.73%-3.05%) in M3T and 4.67%
      (95% confidence interval, 2.28%-9.32%) in the previous model (P=0.03). Compared
      with the previous model, the adjusted odds ratio of stroke for M3T was 0.46 (95%
      confidence interval, 0.12-1.68; P=0.24). M3T was associated with greater
      proportions undergoing carotid ultrasound (P<0.001) and receiving antiplatelet
      therapy (P=0.005). CONCLUSIONS: The M3T system was associated with low 90-day
      stroke outcome in transient ischemic attack patients, providing proof of concept
      that these patients may be managed safely without routine hospital admission
      using a closely supervised protocol in the emergency department.

PMID- 22984017
TI  - Rapid fingerprint analysis of Ligusticum chuanxiong by UFLC-DAD.
AB  - In the present study, a rapid fingerprint analysis of Ligusticum chuanxiong (L.
      chuanxiong) was developed based on ultra-fast liquid chromatography coupled with
      diode array detection (UFLC-DAD). The analysis time was shortened from
      approximately 75 min on conventional high-performance liquid chromatography
      (HPLC) to 40 min on UFLC. This method was validated in terms of stability [<4.40%
      relative standard deviation (RSD)], precision (<4.26% RSD) and repeatability
      (<2.82% RSD). Six batches of L. chuanxiong from different sources were analyzed
      by UFLC-DAD, and the results were systematically processed using professional
      analytical software that was recommended by the State Food and Drug
      Administration of China. The similarities of these six batches of samples were
      evaluated. Compared to conventional HPLC, the UFLC-DAD method was fast and
      sensitive and consumed less solvent, and is widely applicable for quality
      monitoring of traditional Chinese medicine.

PMID- 22984018
TI  - Surgery for primary CNS lymphoma? Challenging a paradigm.
AB  - The standard of care for primary central nervous system lymphoma (PCNSL) is
      systemic chemotherapy with or without whole brain radiotherapy or intrathecal
      chemotherapy. In contrast to treatment for other brain tumors, efforts at
      resection are discouraged. This is a secondary analysis of the German PCNSL Study
      Group-1 trial, a large randomized phase III study comprising 526 patients with
      PCNSL. Progression-free survival (hazard ratio [HR]: 1.39; 95% confidence
      interval [CI]: 1.10-1.74; P = .005) and overall survival (HR: 1.33; 95% CI: 1.04
      1.70; P = .024) were significantly shorter in biopsied patients compared with
      patients with subtotal or gross total resections. This difference in outcome was
      not due to age or Karnofsky performance status (KPS). When controlled for the
      number of lesions, the HR of biopsy versus subtotal or gross total resection
      remained unchanged for progression-free survival (HR = 1.37; P = .009) but was
      smaller for overall survival (HR = 1.27; P = .085). This analysis of the largest
      PCNSL trial ever performed challenges the traditional view that the extent of
      resection has no prognostic impact on this disease. Therefore, we propose to
      reconsider the statement that efforts at resection should be discouraged, at
      least if resection seems safe, as is often the case in treatment of single PCNSL
      lesions.

PMID- 22984019
TI  - Predicting new and persistent asthma.

PMID- 22984020
TI  - Is the best offense a good D-fense? Should we use vitamin D as adjunctive therapy
      for asthma?

PMID- 22984021
TI  - Leading neutrophils to the alveoli: who is the guider?

PMID- 22984022
TI  - Epigenomics of idiopathic pulmonary fibrosis: evaluating the first steps.

PMID- 22984023
TI  - Pentraxin 3 in primary graft dysfunction: the long and short of it.

PMID- 22984024
TI  - Mycobacterium avium complex lung disease therapy.

PMID- 22984025
TI  - Gastrobronchial fistula after a diagnosis of pneumonia.

PMID- 22984026
TI  - Metabolic syndrome biomarkers in prediction of lung function impairment.

PMID- 22984027
TI  - Airway smooth muscle hypertrophy and hyperplasia in asthma.

PMID- 22984029
TI  - Sleep-disordered breathing after combined heart-lung transplantation.

PMID- 22984030
TI  - An unusual case of hiatus hernia contributing to slow respiratory wean in the
      intensive care unit.

PMID- 22984031
TI  - The masterful description of pulmonary tuberculosis by Soranus of Ephesus (c. 98
      138 A.D.).

PMID- 22984032
TI  - Yellow nail syndrome.

PMID- 22984033
TI  - The dual-use conundrum.

PMID- 22984038
TI  - Archaeology. Time ticks away for ancient Afghan monasteries.

PMID- 22984039
TI  - Mass extinctions. Before the dinosaurs' demise, a clambake extinction?

PMID- 22984040
TI  - GM research. Charges fly, confusion reigns over golden rice study in Chinese
      children.

PMID- 22984041
TI  - Scientific misconduct. Government sanctions Harvard psychologist.

PMID- 22984042
TI  - U.S. elections. In a torrent of campaign rhetoric, hints of science policy.

PMID- 22984043
TI  - Particle physics. Who invented the Higgs boson?

PMID- 22984044
TI  - Particle physics. Why the 'Higgs'?

PMID- 22984045
TI  - Particle physics. Symmetries and forces.

PMID- 22984046
TI  - Particle physics. Spontaneous symmetry breaking decanted.

PMID- 22984047
TI  - Bioacoustics. The sound in the silence: discovering a fish's soundscape.

PMID- 22984048
TI  - Paying for tissue: the case of WI-38.

PMID- 22984049
TI  - Paying for tissue: net benefits.

PMID- 22984053
TI  - Comment on "Climate sensitivity estimated from temperature reconstructions of the
      Last Glacial Maximum".
AB  - Schmittner et al. (Reports, 9 December 2011, p. 1385) report a new, low estimate
      of equilibrium climate sensitivity based on a comparison of Last Glacial Maximum
      climate model simulations and paleoproxy data. Here, we show that exclusion of
      questionable comparison points and constructive changes to model design are both
      likely capable of altering the most probable value of equilibrium climate
      sensitivity suggested in Schmittner et al.

PMID- 22984055
TI  - Science and industry. Federal laboratory-business commercialization partnerships.

PMID- 22984056
TI  - Immunology. Orchestrating inflammasomes.

PMID- 22984057
TI  - Cell biology. Staging membrane fusion.

PMID- 22984058
TI  - Neuroscience. The emerging biology of autism spectrum disorders.

PMID- 22984059
TI  - Materials science. Building research equipment with free, open-source hardware.

PMID- 22984060
TI  - Ecology. When paths to cooperation converge.

PMID- 22984061
TI  - Chemistry. Discriminating chemical bonds.

PMID- 22984062
TI  - Retrospective. Sir Bernard Lovell (1913-2012).

PMID- 22984063
TI  - Rinderpest eradication: appropriate technology and social innovations.
AB  - Rinderpest is only the second infectious disease to have been globally
      eradicated. In the final stages of eradication, the virus was entrenched in
      pastoral areas of the Greater Horn of Africa, a region with weak governance, poor
      security, and little infrastructure that presented profound challenges to
      conventional control methods. Although the eradication process was a development
      activity rather than scientific research, its success owed much to several
      seminal research efforts in vaccine development and epidemiology and showed what
      scientific decision-making and management could accomplish with limited
      resources. The keys to success were the development of a thermostable vaccine and
      the application of participatory epidemiological techniques that allowed
      veterinary personnel to interact at a grassroots level with cattle herders to
      more effectively target control measures.

PMID- 22984064
TI  - Adaptive prolonged postreproductive life span in killer whales.
AB  - Prolonged life after reproduction is difficult to explain evolutionarily unless
      it arises as a physiological side effect of increased longevity or it benefits
      related individuals (i.e., increases inclusive fitness). There is little evidence
      that postreproductive life spans are adaptive in nonhuman animals. By using
      multigenerational records for two killer whale (Orcinus orca) populations in
      which females can live for decades after their final parturition, we show that
      postreproductive mothers increase the survival of offspring, particularly their
      older male offspring. This finding may explain why female killer whales have
      evolved the longest postreproductive life span of all nonhuman animals.

PMID- 22984065
TI  - Octet-line node structure of superconducting order parameter in KFe2As2.
AB  - In iron-pnictide superconductivity, the interband interaction between the hole
      and electron Fermi surfaces (FSs) is believed to play an important role. However,
      KFe(2)As(2) has three zone-centered hole FSs and no electron FS but still
      exhibits superconductivity. Our ultrahigh-resolution laser angle-resolved
      photoemission spectroscopy unveils that KFe(2)As(2) is a nodal s-wave
      superconductor with highly unusual FS-selective multi-gap structure: a nodeless
      gap on the inner FS, an unconventional gap with "octet-line nodes" on the middle
      FS, and an almost-zero gap on the outer FS. This gap structure may arise from the
      frustration between competing pairing interactions on the hole FSs causing the
      eightfold sign reversal. Our results suggest that the A(1g) superconducting
      symmetry is universal in iron-pnictides, in spite of the variety of gap
      functions.

PMID- 22984066
TI  - Oxidative aliphatic C-H fluorination with fluoride ion catalyzed by a manganese
      porphyrin.
AB  - Despite the growing importance of fluorinated organic compounds in drug
      development, there are no direct protocols for the fluorination of aliphatic C-H
      bonds using conveniently handled fluoride salts. We have discovered that a
      manganese porphyrin complex catalyzes alkyl fluorination by fluoride ion under
      mild conditions in conjunction with stoichiometric oxidation by iodosylbenzene.
      Simple alkanes, terpenoids, and even steroids were selectively fluorinated at
      otherwise inaccessible sites in 50 to 60% yield. Decalin was fluorinated
      predominantly at the C2 and C3 methylene positions. Bornyl acetate was converted
      to exo-5-fluoro-bornyl acetate, and 5alpha-androstan-17-one was fluorinated
      selectively in the A ring. Mechanistic analysis suggests that the
      regioselectivity for C-H bond cleavage is directed by an oxomanganese(V)
      catalytic intermediate followed by F delivery via an unusual manganese(IV)
      fluoride that has been isolated and structurally characterized.

PMID- 22984067
TI  - Bond-order discrimination by atomic force microscopy.
AB  - We show that the different bond orders of individual carbon-carbon bonds in
      polycyclic aromatic hydrocarbons and fullerenes can be distinguished by
      noncontact atomic force microscopy (AFM) with a carbon monoxide (CO)
      functionalized tip. We found two different contrast mechanisms, which were
      corroborated by density functional theory calculations: The greater electron
      density in bonds of higher bond order led to a stronger Pauli repulsion, which
      enhanced the brightness of these bonds in high-resolution AFM images. The
      apparent bond length in the AFM images decreased with increasing bond order
      because of tilting of the CO molecule at the tip apex.

PMID- 22984068
TI  - Glacier extent during the Younger Dryas and 8.2-ka event on Baffin Island, Arctic
      Canada.
AB  - Greenland ice cores reveal that mean annual temperatures during the Younger Dryas
      (YD) cold interval--about 12.9 to 11.7 thousand years ago (ka)--and the ~150-year
      long cold reversal that occurred 8.2 thousand years ago were ~15 degrees  and 3
      degrees  to 4 degrees C colder than today, respectively. Reconstructing ice-sheet
      response to these climate perturbations can help evaluate ice-sheet sensitivity
      to climate change. Here, we report the widespread advance of Laurentide Ice Sheet
      outlet glaciers and independent mountain glaciers on Baffin Island, Arctic
      Canada, in response to the 8.2-ka event and show that mountain glaciers during
      the 8.2-ka event were larger than their YD predecessors. In contrast to the
      wintertime bias of YD cooling, we suggest that cooling during the 8.2-ka event
      was more evenly distributed across the seasons.

PMID- 22984069
TI  - Initiation of cell wall pattern by a Rho- and microtubule-driven symmetry
      breaking.
AB  - A specifically patterned cell wall is a determinant of plant cell shape. Yet, the
      precise mechanisms that underlie initiation of cell wall patterning remain
      elusive. By using a reconstitution assay, we revealed that ROPGEF4 (Rho of plant
      guanine nucleotide exchange factor 4) and ROPGAP3 [ROP guanosine triphosphatase
      (GTPase)-activating protein 3] mediate local activation of the plant Rho GTPase
      ROP11 to initiate distinct pattern of secondary cell walls in xylem cells. The
      activated ROP11 recruits MIDD1 to induce local disassembly of cortical
      microtubules. Conversely, cortical microtubules eliminate active ROP11 from the
      plasma membrane through MIDD1. Such a mutual inhibitory interaction between
      active ROP domains and cortical microtubules establishes the distinct pattern of
      secondary cell walls. This Rho-based regulatory mechanism shows how plant cells
      initiate and control cell wall patterns to form various cell shapes.

PMID- 22984070
TI  - A killer-protector system regulates both hybrid sterility and segregation
      distortion in rice.
AB  - Hybrid sterility is a major form of postzygotic reproductive isolation that
      restricts gene flow between populations. Cultivated rice (Oryza sativa L.)
      consists of two subspecies, indica and japonica; inter-subspecific hybrids are
      usually sterile. We show that a killer-protector system at the S5 locus encoded
      by three tightly linked genes [Open Reading Frame 3 (ORF3) to ORF5] regulates
      fertility in indica-japonica hybrids. During female sporogenesis, the action of
      ORF5+ (killer) and ORF4+ (partner) causes endoplasmic reticulum (ER) stress.
      ORF3+ (protector) prevents ER stress and produces normal gametes, but ORF3-
      cannot prevent ER stress, resulting in premature programmed cell death and leads
      to embryo-sac abortion. Preferential transmission of ORF3+ gametes results in
      segregation distortion in the progeny. These results add to our understanding of
      differences between indica and japonica rice and may aid in rice genetic
      improvement.

PMID- 22984071
TI  - Structural probing of a protein phosphatase 2A network by chemical cross-linking
      and mass spectrometry.
AB  - The identification of proximate amino acids by chemical cross-linking and mass
      spectrometry (XL-MS) facilitates the structural analysis of homogeneous protein
      complexes. We gained distance restraints on a modular interaction network of
      protein complexes affinity-purified from human cells by applying an adapted XL-MS
      protocol. Systematic analysis of human protein phosphatase 2A (PP2A) complexes
      identified 176 interprotein and 570 intraprotein cross-links that link specific
      trimeric PP2A complexes to a multitude of adaptor proteins that control their
      cellular functions. Spatial restraints guided molecular modeling of the binding
      interface between immunoglobulin binding protein 1 (IGBP1) and PP2A and revealed
      the topology of TCP1 ring complex (TRiC) chaperonin interacting with the PP2A
      regulatory subunit 2ABG. This study establishes XL-MS as an integral part of
      hybrid structural biology approaches for the analysis of endogenous protein
      complexes.

PMID- 22984072
TI  - Global gene deletion analysis exploring yeast filamentous growth.
AB  - The dimorphic switch from a single-cell budding yeast to a filamentous form
      enables Saccharomyces cerevisiae to forage for nutrients and the opportunistic
      pathogen Candida albicans to invade human tissues and evade the immune system. We
      constructed a genome-wide set of targeted deletion alleles and introduced them
      into a filamentous S. cerevisiae strain, Sigma1278b. We identified genes involved
      in morphologically distinct forms of filamentation: haploid invasive growth,
      biofilm formation, and diploid pseudohyphal growth. Unique genes appear to
      underlie each program, but we also found core genes with general roles in
      filamentous growth, including MFG1 (YDL233w), whose product binds two
      morphogenetic transcription factors, Flo8 and Mss11, and functions as a critical
      transcriptional regulator of filamentous growth in both S. cerevisiae and C.
      albicans.

PMID- 22984073
TI  - A critical period for social experience-dependent oligodendrocyte maturation and
      myelination.
AB  - Early social isolation results in adult behavioral and cognitive dysfunction that
      correlates with white matter alterations. However, how social deprivation
      influences myelination and the significance of these myelin defects in the adult
      remained undefined. We show that mice isolated for 2 weeks immediately after
      weaning have alterations in prefrontal cortex function and myelination that do
      not recover with reintroduction into a social environment. These alterations,
      which occur only during this critical period, are phenocopied by loss of
      oligodendrocyte ErbB3 receptors, and social isolation leads to reduced expression
      of the ErbB3 ligand neuregulin-1. These findings indicate that social experience
      regulates prefrontal cortex myelination through neuregulin-1/ErbB3 signaling and
      that this is essential for normal cognitive function, thus providing a cellular
      and molecular context to understand the consequences of social isolation.

PMID- 22984074
TI  - Active DNA demethylation in plant companion cells reinforces transposon
      methylation in gametes.
AB  - The Arabidopsis thaliana central cell, the companion cell of the egg, undergoes
      DNA demethylation before fertilization, but the targeting preferences, mechanism,
      and biological significance of this process remain unclear. Here, we show that
      active DNA demethylation mediated by the DEMETER DNA glycosylase accounts for all
      of the demethylation in the central cell and preferentially targets small, AT
      rich, and nucleosome-depleted euchromatic transposable elements. The vegetative
      cell, the companion cell of sperm, also undergoes DEMETER-dependent demethylation
      of similar sequences, and lack of DEMETER in vegetative cells causes reduced
      small RNA-directed DNA methylation of transposons in sperm. Our results
      demonstrate that demethylation in companion cells reinforces transposon
      methylation in plant gametes and likely contributes to stable silencing of
      transposable elements across generations.

PMID- 22984075
TI  - The importance of the Erk pathway in the development of linker for activation of
      T cells-mediated autoimmunity.
AB  - The ability of the transmembrane adaptor protein linker for activation of T cells
      (LAT) to regulate T cell development, activation, survival, and homeostasis
      depends upon phosphorylation of its multiple tyrosine residues. The mutation of
      tyrosine 136 on LAT abrogates its interaction with phospholipase C-gamma1,
      causing severe ramifications on TCR-mediated signaling. Mice harboring this
      mutation, LATY136F mice, have significantly impaired thymocyte development;
      however, they rapidly develop a fatal lymphoproliferative disease marked by the
      uncontrolled expansion of Th2-skewed CD4(+) T cells, high levels of IgE and IgG1,
      and autoantibody production. In this study, we assessed the contribution of
      multiple signaling pathways in LATY136F disease development. The deletion of the
      critical signaling proteins Gads and RasGRP1 caused a further block in thymocyte
      development, but, over time, could not prevent CD4(+) T cell hyperproliferation.
      Also, restoring signaling through the NF-kappaB and NFAT pathways was unable to
      halt the development of disease. However, expression of a constitutively active
      Raf transgene enhanced lymphoproliferation, indicating a role for the Ras-MAPK
      pathway in LAT-mediated disease.

PMID- 22984076
TI  - Cell-intrinsic abrogation of TGF-beta signaling delays but does not prevent
      dysfunction of self/tumor-specific CD8 T cells in a murine model of autochthonous
      prostate cancer.
AB  - Adoptive T cell therapy (ACT) for the treatment of established cancers is
      actively being pursued in clinical trials. However, poor in vivo persistence and
      maintenance of antitumor activity of transferred T cells remain major problems.
      TGF-beta is a potent immunosuppressive cytokine that is often expressed at high
      levels within the tumor microenvironment, potentially limiting T cell-mediated
      antitumor activity. In this study, we used a model of autochthonous murine
      prostate cancer to evaluate the effect of cell-intrinsic abrogation of TGF-beta
      signaling in self/tumor-specific CD8 T cells used in ACT to target the tumor in
      situ. We found that persistence and antitumor activity of adoptively transferred
      effector T cells deficient in TGF-beta signaling were significantly improved in
      the cancerous prostate. However, over time, despite persistence in peripheral
      lymphoid organs, the numbers of transferred cells in the prostate decreased and
      the residual prostate-infiltrating T cells were no longer functional. These
      findings reveal that TGF-beta negatively regulates the accumulation and effector
      function of transferred self/tumor-specific CD8 T cells and highlight that, when
      targeting a tumor Ag that is also expressed as a self-protein, additional
      substantive obstacles are operative within the tumor microenvironment,
      potentially hampering the success of ACT for solid tumors.

PMID- 22984077
TI  - Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17
      but enhances regulatory T cell differentiation.
AB  - The immunoproteasome generates peptides presented on MHC class I molecules to
      cytotoxic T cells. ONX 0914 (formerly called PR-957) is a selective inhibitor of
      the immunoproteasome subunit low molecular mass polypeptide (LMP) 7 (beta5i) that
      attenuates disease progression in mouse models of diabetes, colitis, and
      arthritis. The aim of this study was to investigate the effect of LMP7-specific
      inhibition on major Th cell differentiation pathways involved in the progression
      of autoimmune diseases in vitro and in vivo. We used ONX 0914-treated wild-type
      CD4(+) T cells and also LMP7(-/-) CD4(+) T cells under different Th cell
      polarizing conditions, focusing on the effector cytokines and transcription
      factors involved, and compared them with wild-type CD4(+) T cells. Mouse models
      of dextran sodium sulfate-induced colitis and a T cell transfer model of colitis
      were used for in vivo assessment. Deletion or inhibition of LMP7 suppressed
      generation of Th17 but promoted regulatory T cell (Treg) development. In
      developing Th17 cells, immunoproteasome inhibition blocked phosphorylation of
      STAT3, whereas in Tregs, SMAD phosphorylation was enhanced. Additionally, LMP7
      inhibition led to reduced STAT1 phosphorylation and Th1 differentiation. These
      findings were confirmed in vivo as LMP7 inhibition or deficiency resulted in
      reduced Th1 and Th17 expansion while promoting Treg development in dextran sodium
      sulfate-induced colitis. Also, in a T cell-dependent transfer model of colitis,
      LMP7-specific inhibition led to reduced Th1 and Th17 differentiation in vivo.
      LMP7 governs Th cell lineage determination by affecting the balance of receptor
      proximal signals during differentiation. These data render LMP7 a promising drug
      target for the treatment of autoimmune diseases.

PMID- 22984078
TI  - Protective immunity against pulmonary cryptococcosis is associated with STAT1
      mediated classical macrophage activation.
AB  - Experimental pulmonary Cryptococcus neoformans infection in BALB/c mice is
      associated with polarized Th2-type cytokine production, alternative macrophage
      activation, and severe bronchopneumonia. In contrast, pulmonary infection with a
      C. neoformans strain that secretes IFN-gamma, H99gamma, elicits Th1-type cytokine
      production and classical macrophage activation. Additionally, mice infected with
      H99gamma resolve the acute infection and are subsequently protected against
      challenge with wild-type C. neoformans. The present study characterizes
      macrophage activation during the protective response to wild-type C. neoformans
      in mice previously immunized with H99gamma. We observed increased pulmonary Th1
      type cytokine production in lung homogenates and classical macrophage activation
      as evidenced by enhanced expression of inducible NO synthase in the lungs of
      H99gamma-immunized mice compared with mice given a nonprotective immunization
      with heat-killed C. neoformans (HKCn). Furthermore, macrophages isolated from
      H99gamma-immunized mice on day 7 postchallenge and cultured in vitro were
      fungistatic against C. neoformans, whereas cryptococcal growth was uncontrolled
      within macrophages from HKCn-immunized mice. Th2-type cytokine production and
      induction of alternatively activated macrophages were also observed in lungs of
      HKCn-immunized mice during rechallenge. Gene expression arrays showed that
      classical macrophage activation during challenge infection in H99gamma-immunized
      mice was associated with induction of the transcription factor STAT1 and its
      downstream targets IFN regulatory factor-1, suppressor of cytokine signaling-1,
      CXCL9, and CXCL10. These studies demonstrate that protective responses to C.
      neoformans challenge in immunized mice include classical macrophage activation
      and enhanced macrophage fungistasis of C. neoformans yeasts. Finally, the
      classical activation phenotype of protective anticryptococcal macrophages is
      likely mediated via STAT1 signal transduction pathways.

PMID- 22984079
TI  - ATP induces protein arginine deiminase 2-dependent citrullination in mast cells
      through the P2X7 purinergic receptor.
AB  - Posttranslational modifications regulate physiology either by directly modulating
      protein function or by impacting immune recognition of self-proteins.
      Citrullination is a posttranslational modification formed by the conversion of
      arginine residues into the citrulline amino acid by protein arginine deiminase
      (PAD) family members. We have identified mast cells as a major source of the PAD2
      enzyme. Activation of the P2X7 purinergic receptor (P2X7) by the inflammatory
      "danger" signal ATP induces PAD2 activity and robust protein citrullination. P2X7
      mediated activation of PAD2 is sensitive to p38 MAPK and protein kinase C
      inhibitors, and PAD2 regulates the expression of the TNFR2, Adamts-9, and Rab6b
      transcripts in mast cells. Further, the PAD2 enzyme and its citrullinated
      substrate proteins are released from mast cells on activation with ATP. PAD2
      expression is closely linked with inflammation in rheumatoid arthritis (RA)
      synovial tissue, and PAD2 and citrullinated proteins are found in the synovial
      fluid of RA patients. In addition, RA is associated with the development of
      autoantibodies to citrullinated self-proteins. Our results suggest that P2X7
      activation of mast cells may play a role in inflammation by providing PAD2 and
      PAD2 substrates access to the extracellular space.

PMID- 22984080
TI  - Receptor cross-talk spatially restricts p-ERK during TLR4 stimulation of
      autoreactive B cells.
AB  - To maintain tolerance, autoreactive B cells must regulate signal transduction
      from the BCR and TLRs. We recently identified that dendritic cells and
      macrophages regulate autoreactive cells during TLR4 activation by releasing IL-6
      and soluble CD40 ligand (sCD40L). These cytokines selectively repress Ab
      secretion from autoreactive, but not antigenically naive, B cells. How IL-6 and
      sCD40L repress autoantibody production is unknown. In this work, we show that IL
      6 and sCD40L are required for low-affinity/avidity autoreactive B cells to
      maintain tolerance through a mechanism involving receptor cross-talk between the
      BCR, TLR4, and the IL-6R or CD40. We show that acute signaling through IL-6R or
      CD40 integrates with chronic BCR-mediated ERK activation to restrict p-ERK from
      the nucleus and represses TLR4-induced Blimp-1 and XBP-1 expression. Tolerance is
      disrupted in 2-12H/MRL/lpr mice where IL-6 and sCD40L fail to spatially restrict
      p-ERK and fail to repress TLR4-induced Ig secretion. In the case of CD40, acute
      signaling in B cells from 2-12H/MRL/lpr mice is intact, but the chronic
      activation of p-ERK emanating from the BCR is attenuated. Re-establishing
      chronically active ERK through retroviral expression of constitutively active
      MEK1 restores tolerance upon sCD40L, but not IL-6, stimulation, indicating that
      regulation by IL-6 requires another signaling effector. These data define the
      molecular basis for the regulation of low-affinity autoreactive B cells during
      TLR4 stimulation; they explain how autoreactive but not naive B cells are
      repressed by IL-6 and sCD40L; and they identify B cell defects in lupus-prone
      mice that lead to TLR4-induced autoantibody production.

PMID- 22984081
TI  - Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL
      1beta production.
AB  - Although microRNA (miRNA) regulation of TLR signaling is well established, this
      has not yet been observed for NLR proteins or the inflammasomes they form. We
      have now validated a highly conserved miR-223 target site in the NLRP3 3'
      untranslated region. miR-223 expression decreases as monocytes differentiate into
      macrophages, whereas NLRP3 protein increases during this time. However,
      overexpression of miR-223 prevents accumulation of NLRP3 protein and inhibits IL
      1beta production from the inflammasome. Virus inhibition of the inflammasome is
      an emerging theme, and we have also identified an EBV miRNA that can target the
      miR-223 binding site in the NLRP3 3'-untranslated region. Furthermore, this virus
      miRNA can be secreted from infected B cells via exosomes to inhibit the NLRP3
      inflammasome in noninfected cells. Therefore, we have identified both the first
      endogenous miRNA that limits NLRP3 inflammatory capacity during myeloid cell
      development and also a viral miRNA that takes advantage of this, limiting
      inflammation for its own purposes.

PMID- 22984082
TI  - NLRP3 inflammasome activity is negatively controlled by miR-223.
AB  - Inflammasomes are multiprotein signaling platforms that form upon sensing microbe
      or damage-associated molecular patterns. Upon their formation, caspase-1 is
      activated, leading to the processing of certain proinflammatory cytokines and the
      initiation of a special type of cell death, known as pyroptosis. Among known
      inflammasomes, NLRP3 takes on special importance because it appears to be a
      general sensor of cell stress. Moreover, unlike other inflammasome sensors, NLRP3
      inflammasome activity is under additional transcriptional regulation. In this
      study, we identify the myeloid-specific microRNA miR-223 as another critical
      regulator of NLRP3 inflammasome activity. miR-223 suppresses NLRP3 expression
      through a conserved binding site within the 3' untranslated region of NLRP3,
      translating to reduced NLRP3 inflammasome activity. Although miR-223 itself is
      not regulated by proinflammatory signals, its expression varies among different
      myeloid cell types. Therefore, given the tight transcriptional control of NLRP3
      message itself, miR-223 functions as an important rheostat controlling NLRP3
      inflammasome activity.

PMID- 22984084
TI  - Second tests for Chlamydia trachomatis and Neisseria gonorrhoeae.

PMID- 22984083
TI  - Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B
      cells.
AB  - Phagocyte NADPH oxidase plays a key role in pathogen clearance via reactive
      oxygen species (ROS) production. Defects in oxidase function result in chronic
      granulomatous disease with hallmark recurrent microbial infections and
      inflammation. The oxidase's role in the adaptive immune response is not well
      understood. Class II presentation of cytoplasmic and exogenous Ag to CD4(+) T
      cells was impaired in human B cells with reduced oxidase p40(phox) subunit
      expression. Naturally arising mutations, which compromise p40(phox) function in a
      chronic granulomatous disease patient, also perturbed class II Ag presentation
      and intracellular ROS production. Reconstitution of patient B cells with a wild
      type, but not a mutant, p40(phox) allele restored exogenous Ag presentation and
      intracellular ROS generation. Remarkably, class II presentation of epitopes from
      membrane Ag was robust in p40(phox)-deficient B cells. These studies reveal a
      role for NADPH oxidase and p40(phox) in skewing epitope selection and T cell
      recognition of self Ag.

PMID- 22984085
TI  - Comparative effectiveness of a rapid point-of-care test for detection of
      Chlamydia trachomatis among women in a clinical setting.
AB  - OBJECTIVES: To compare the effectiveness and cost-effectiveness of a promising
      new point-of-care (POC) chlamydia test with traditional nucleic acid
      amplification testing (NAAT), and to determine the characteristics that would
      make a POC test most cost-effective. METHODS: A decision tree was constructed to
      model chlamydia screening visits to a sexually transmitted disease clinic by a
      hypothetical cohort of 10,000 women. The model incorporated programmatic
      screening costs, treatment costs and medical costs averted through prevention of
      pelvic inflammatory disease (PID) and its sequelae. Parameter values and costs
      were estimated for each node in the decision tree based on primary data,
      published data and unpublished health data. RESULTS: For the base-case scenario
      (POC sensitivity 92.9%; 47.5% of women willing to wait 40 min for test results;
      test cost $33.48), POC was estimated to save US$5050 for each case of PID averted
      compared with NAAT. One-way sensitivity analyses indicated that POC would
      dominate NAAT if the POC test cost is <US$41.52 or if POC sensitivity is >=
      87.1%. In a probabilistic sensitivity analysis (Monte Carlo simulations, 10 000
      iterations), 10.8% of iterations indicated that the POC strategy dominated the
      NAAT strategy. The mean incremental cost-effectiveness ratio indicated that the
      POC strategy would save US$28 in total, and avert 14 PID cases. CONCLUSIONS: A
      promising new chlamydia POC test is likely to be cost-effective compared with
      traditional NAAT. The POC test sensitivity, cost and proportion of women willing
      to wait for the POC test result are key elements to determining the cost
      effectiveness of any new POC test strategy.

PMID- 22984086
TI  - In vivo imaging of tracheal epithelial cells in mice during airway regeneration.
AB  - Many human lung diseases, such as asthma, chronic obstructive pulmonary disease,
      bronchiolitis obliterans, and cystic fibrosis, are characterized by changes in
      the cellular composition and architecture of the airway epithelium. Intravital
      fluorescence microscopy has emerged as a powerful approach in mechanistic studies
      of diseases, but it has been difficult to apply this tool for in vivo respiratory
      cell biology in animals in a minimally invasive manner. Here, we describe a novel
      miniature side-view confocal probe capable of visualizing the epithelium in the
      mouse trachea in vivo at a single-cell resolution. We performed serial real-time
      endotracheal fluorescence microscopy in live transgenic reporter mice to view the
      three major cell types of the large airways, namely, basal cells, Clara cells,
      and ciliated cells. As a proof-of-concept demonstration, we monitored the
      regeneration of Clara cells over 18 days after a sulfur dioxide injury. Our
      results show that in vivo tracheal microscopy offers a new approach in the study
      of altered, regenerating, or metaplastic airways in animal models of lung
      diseases.

PMID- 22984087
TI  - CD8(+) T cells responding to alveolar self-antigen lack CD25 expression and fail
      to precipitate autoimmunity.
AB  - Although the contribution of CD8(+) T cells to the pathogenesis of
      noncommunicable lung diseases has become increasingly appreciated, our knowledge
      about the mechanisms controlling self-reactive CD8(+) T cells in the respiratory
      tract remains largely elusive. The outcome of the encounter between pulmonary
      self-antigen and naive CD8(+) T cells, in the presence or absence of
      inflammation, was traced after adoptive transfer of fluorescence-labeled CD8(+) T
      cells specific for the neo-self-antigen influenza A hemagglutinin into transgenic
      mice expressing hemagglutinin specifically in alveolar type II epithelial cells
      in order: to study the outcome of alveolar antigen encounter in the steady state
      and under inflammatory conditions; to define the phenotype and fate of CD8(+) T
      cells primed in the respiratory tract; and, finally, to correlate these findings
      with the onset of autoimmunity in the lung. We found that CD8(+) T cells remain
      ignorant in the steady state, whereas transient proliferation of self-reactive
      CD8(+) T cells is induced by forced maturation or licensing of dendritic cells,
      increases in the antigenic threshold, and targeted release of alveolar self
      antigen by epithelial injury. However, these cells fail to acquire effector
      functions, lack the expression of the high-affinity IL-2 receptor CD25, and do
      not precipitate autoimmunity in the lung. We conclude that inadvertent activation
      of CD8(+) T cells in the lung is prevented in the absence of "danger signals,"
      whereas tissue damage after infection or noninfectious inflammation creates an
      environment that allows the priming of previously ignorant T cells. Failure in
      effector cell differentiation after abortive priming, however, precludes the
      establishment of self-perpetuating autoimmunity in the lung.

PMID- 22984089
TI  - From Alzheimer's disease retrogenesis: a new care strategy for patients with
      advanced dementia.
AB  - There is evidence that exercise may reduce the progressive cognitive dysfunction
      of Alzheimer's disease (AD). However, no previous investigation has studiethe
      acute effects of adapted games (AG) on patients with AD. The aim of this study
      was to examine the acute effects of AG on the agitated behavior (rating scale
      Agitated Behavior Rating Scale [ABRS]) and cognitive performance (Test for Severe
      Impairment [TSI]) of patients with advanced dementia. Twenty patients (83+/-4
      yrs) participated in AG and placebo activities (PL). Agitated behavior and
      cognitive performance were compared before and after 30 minutes of AG and PL. In
      the hour after the AG, agitated behavior decreased by ~4 ABRS points and
      cognitive performance increased by ~5 TSI points. On the contrary, after PL we
      found no change in agitated behavior or cognitive performance. Our data indicate
      that AG can momentarily reduce agitated behavior and increase the cognitive
      performance in participants with AD.

PMID- 22984090
TI  - The effects of different attentional demands in the identification of emotional
      facial expressions in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by the progressive impairment of mental
      and emotional functions, including the processing of emotional facial expression
      (EFE). Deficits in decoding EFE are relevant in social contexts in which
      information from 2 or more sources may be processed simultaneously. To assess the
      role of contextual stimuli on EFE processing in AD, we analyzed the ability of
      patients with AD and healthy elderly adults to identify EFE when simultaneously
      performing another task. Each of the 6 basic EFEs was presented to 15 patients
      with AD and 35 controls in a dual task paradigm that is in parallel with a
      visuospatial or a semantic task. Results show that the decoding of EFEs was
      impaired in patients with AD when they were simultaneously processing additional
      visuospatial information, yet not when they were performed in conjunction with a
      semantic task. These findings suggest that the capacity to interpret emotional
      states is impaired in AD.

PMID- 22984088
TI  - Regulation and functional significance of autophagy in respiratory cell biology
      and disease.
AB  - Autophagy is a homeostatic process common to all eukaryotic cells that serves to
      degrade intracellular components. Among three classes of autophagy,
      macroautophagy is best understood, and is the subject of this Review. The
      function of autophagy is multifaceted, and includes removal of long-lived
      proteins and damaged or unneeded organelles, recycling of intracellular
      components for nutrients, and defense against pathogens. This process has been
      extensively studied in yeast, and understanding of its functional significance in
      human disease is also increasing. This Review explores the basic machinery and
      regulation of autophagy in mammalian systems, methods employed to measure
      autophagic activity, and then focuses on recent discoveries about the functional
      significance of autophagy in respiratory diseases, including chronic obstructive
      pulmonary disease, cystic fibrosis, tuberculosis, idiopathic pulmonary fibrosis,
      pulmonary arterial hypertension, acute lung injury, and lymphangioleiomyomatosis.

PMID- 22984091
TI  - Tolvaptan improves left ventricular dysfunction after myocardial infarction in
      rats.
AB  - BACKGROUND: Arginine vasopressin, which promotes the reabsorption of renal water
      is increased in chronic heart failure. Here, we compared the effects of
      tolvaptan, a newly developed nonpeptide V(2) receptor antagonist, with those of
      furosemide, a loop diuretic, and a combination of these 2 agents in rats with
      left ventricular dysfunction after myocardial infarction (MI). METHODS AND
      RESULTS: After 10 weeks of MI induction, the rats were separated them into the
      following 6 groups adjusted to the infarct size: a vehicle group, a group treated
      with 15 mg.kg(-1).day(-1) of furosemide, 2 groups treated with 3 or 10 mg.kg(
      1).day(-1) of tolvaptan; and 2 groups treated with 15 mg.kg(-1).day(-1) of
      furosemide plus 3 or 10 mg.kg(-1).day(-1) tolvaptan. Each treatment agent was
      administered for 4 weeks, and all groups had similar blood pressure levels and
      infarct size. The tolvaptan-treated groups were found to have lower levels of
      left ventricular end-diastolic and systolic cardiac volumes than the vehicle
      group did. Furthermore, the improvement in the ejection fraction in the tolvaptan
      treated groups was significantly greater than those in the vehicle group. ED-1
      immunostaining and Sirius red staining revealed that tolvaptan significantly
      repressed MI-induced macrophage infiltration and interstitial fibrosis in the
      left ventricle, respectively. Tolvaptan attenuated the MI-induced mRNA
      expressions of atrial and brain natriuretic peptides, monocyte chemotactic
      protein-1, transforming growth factor-beta1, arginine vasopressin V(1a) receptor,
      and endothelin-1 in the marginal infarct region. CONCLUSIONS: Tolvaptan may
      improve cardiac dysfunction after MI, which is partially mediated by the
      suppression of V(1a) receptor, neurohumoral activation and inflammation.

PMID- 22984092
TI  - Integrating quality improvement into continuing medical education activities
      within a community hospital system.
AB  - The integration of the Mercy Health System's quality improvement (QI) and
      continuing medical educational (CME) activities is described. With the
      implementation of computerized medical data, the opportunities for QI-focused CME
      are growing. The authors reviewed their regularly scheduled series and special
      CME programs to assess their impact on quality care processes. Clinical
      improvements were affected by combining national guidelines and advancements with
      local clinical data and interactions with physicians within interdisciplinary as
      well as specialty conferences. Case-based, multidisciplinary conferences lent
      themselves to this process to a greater extent than didactic conferences. The
      latter also could lead to QI when the topics were focused on specific quality
      initiatives that often are part of a national QI initiative. Although the authors
      consider these efforts to be at an intermediate stage of development, they have
      observed several QI/patient safety process improvements.

PMID- 22984093
TI  - The importance of ecological constraints on the control of multi-species treeline
      dynamics in eastern Nunavik, Quebec.
AB  - PREMISE OF THE STUDY: Treelines are temperature-sensitive ecotones that should
      be able to expand in response to global warming; however, they are also
      controlled by ecological constraints. These constraints can create bottlenecks
      for tree regeneration, hindering treeline advances. Near Kangiqsualujjuaq
      (Nunavik, subarctic Quebec), previous studies suggested successful recruitment of
      Larix laricina above the altitudinal treeline, while Picea mariana establishment
      remains scarce. We studied regeneration of both species to identify factors
      responsible for such contrasting responses. * METHODS: We measured seeds and
      wings to evaluate species dispersal potential. We compared seed viability and
      tolerance to shrub leachates with germination trials. To evaluate seedbed
      preferences, we compared seedling occurrence on the different seedbeds with
      seedbed relative abundance in the field. * KEY RESULTS: Seed germination was
      similar between L. laricina and P. mariana, whereas dispersal potential was
      higher for the latter. Germination of P. mariana seeds was more strongly
      inhibited by shrub leachates than were L. laricina seeds. In the field, we found
      only a few Picea seedlings, but numerous seedlings of Larix had established
      disproportionally on several seedbeds. While Betula glandulosa, mosses, and
      Vaccinium uliginosim impeded Larix establishment, numerous seedlings were found
      on lichens, mineral soil, and liverworts. The low occurrence of suitable seedbeds
      for Picea, mainly mineral soil, could explain the seedling scarcity of this
      species. * CONCLUSIONS: This study highlighted that allelopathy and unsuitable
      seedbeds could contribute to regeneration failure of P. mariana in eastern
      Nunavik and emphasizes the need to consider ecological preferences of species
      before predicting treeline expansion under a warmer climate.

PMID- 22984094
TI  - Escaping the lianoid habit: evolution of shrub-like growth forms in Aristolochia
      subgenus Isotrema (Aristolochiaceae).
AB  - PREMISE OF THE STUDY: A large range of growth forms is a notable aspect of
      angiosperm diversity and arguably a key element of their success. However, few
      studies within a phylogenetic context have explored how anatomical,
      developmental, and biomechanical traits are linked with growth form evolution.
      Aristolochia (~500 species) consists predominantly of climbers, but a handful of
      shrub-like species are known from Aristolochia subgenus Isotrema (hereafter,
      shortened to Isotrema). We test hypotheses proposing that the establishment of
      functional traits linked to lianescence might limit the ability to evolve
      structurally diverse growth forms, particularly self-supporting forms. * METHODS:
      We focus on the origin of the shrub habit in Isotrema, from which we sampled
      representatives from climbing to self-supporting forms. Morphological,
      anatomical, and biomechanical characters are optimized on a chloroplast- and
      nuclear-derived phylogeny. * KEY RESULTS: Character-state reconstructions
      revealed that the climbing habit is plesiomorphic in Isotrema and shrub-like
      forms are derived from climbers. However, shrubs do not constitute a monophyletic
      group. Both shrubs and climbers show large multiseriate rays, but differ in terms
      of vessel size and proportion of fibers and soft tissues. * CONCLUSION: We
      suggest that while shrub-like species might have partly escaped from the
      constraints of life as lianas; their height size and stability are not typical of
      self-supporting shrubs and trees. Shrubs retained lianoid stem characters that
      are known to promote flexibility such as ray parenchyma. The transitions to a
      shrub-like form likely involved relatively simple, developmental changes that may
      be attributed to heterochronic processes.

PMID- 22984095
TI  - Leaf- and cell-level carbon cycling responses to a nitrogen and phosphorus
      gradient in two Arctic tundra species.
AB  - PREMISE OF THE STUDY: Consequences of global climate change are detectable in
      the historically nitrogen- and phosphorus-limited Arctic tundra landscape and
      have implications for the terrestrial carbon cycle. Warmer temperatures and
      elevated soil nutrient availability associated with increased microbial activity
      may influence rates of photosynthesis and respiration. * METHODS: This study
      examined leaf-level gas exchange, cellular ultrastructure, and related leaf
      traits in two dominant tundra species, Betula nana, a woody shrub, and Eriophorum
      vaginatum, a tussock sedge, under a 3-yr-old treatment gradient of nitrogen (N)
      and phosphorus (P) fertilization in the North Slope of Alaska. * KEY RESULTS:
      Respiration increased with N and P addition-the highest rates corresponding to
      the highest concentrations of leaf N in both species. The inhibition of
      respiration by light ("Kok effect") significantly reduced respiration rates in
      both species (P < 0.001), ranged from 12-63% (mean 34%), and generally decreased
      with fertilization for both species. However, in both species, observed rates of
      photosynthesis did not increase, and photosynthetic nitrogen use efficiency
      generally decreased under increasing fertilization. Chloroplast and mitochondrial
      size and density were highly sensitive to N and P fertilization (P < 0.001),
      though species interactions indicated divergent cellular organizational
      strategies. * CONCLUSIONS: Results from this study demonstrate a species-specific
      decoupling of respiration and photosynthesis under N and P fertilization,
      implying an alteration of the carbon balance of the tundra ecosystem under future
      conditions.

PMID- 22984097
TI  - National recruitment in dentistry: the orthodontic experience.

PMID- 22984096
TI  - Impact of covariate models on the assessment of the air pollution-mortality
      association in a single- and multipollutant context.
AB  - With the advent of multicity studies, uniform statistical approaches have been
      developed to examine air pollution-mortality associations across cities. To
      assess the sensitivity of the air pollution-mortality association to different
      model specifications in a single and multipollutant context, the authors applied
      various regression models developed in previous multicity time-series studies of
      air pollution and mortality to data from Philadelphia, Pennsylvania (May 1992
      September 1995). Single-pollutant analyses used daily cardiovascular mortality,
      fine particulate matter (particles with an aerodynamic diameter <=2.5 um;
      PM(2.5)), speciated PM(2.5), and gaseous pollutant data, while multipollutant
      analyses used source factors identified through principal component analysis. In
      single-pollutant analyses, risk estimates were relatively consistent across
      models for most PM(2.5) components and gaseous pollutants. However, risk
      estimates were inconsistent for ozone in all-year and warm-season analyses.
      Principal component analysis yielded factors with species associated with
      traffic, crustal material, residual oil, and coal. Risk estimates for these
      factors exhibited less sensitivity to alternative regression models compared with
      single-pollutant models. Factors associated with traffic and crustal material
      showed consistently positive associations in the warm season, while the coal
      combustion factor showed consistently positive associations in the cold season.
      Overall, mortality risk estimates examined using a source-oriented approach
      yielded more stable and precise risk estimates, compared with single-pollutant
      analyses.

PMID- 22984099
TI  - Digital versus plaster study models: how accurate and reproducible are they?
AB  - OBJECTIVE: To compare measurements of occlusal relationships and arch dimensions
      taken from digital study models with those taken from plaster models. DESIGN:
      Laboratory study SETTING: The Orthodontic Department, Kettering General Hospital,
      Kettering, UK Methods and materials: One hundred and twelve sets of study models
      with a range of malocclusions and various degrees of crowding were selected.
      Occlusal features were measured manually with digital callipers on the plaster
      models. The same measurements were performed on digital images of the study
      models. Each method was carried out twice in order to check for intra-operator
      variability. The repeatability and reproducibility of the methods was assessed.
      RESULTS: Statistically significant differences between the two methods were
      found. In 8 of the 16 occlusal features measured, the plaster measurements were
      more repeatable. However, those differences were not of sufficient magnitude to
      have clinical relevance. In addition there were statistically significant
      systematic differences for 12 of the 16 occlusal features, with the plaster
      measurements being greater for 11 of these, indicating the digital model scans
      were not a true 11 representation of the plaster models. CONCLUSIONS: The
      repeatability of digital models compared with plaster models is satisfactory for
      clinical applications, although this study demonstrated some systematic
      differences. Digital study models can therefore be considered for use as an
      adjunct to clinical assessment of the occlusion, but as yet may not supersede
      current methods for scientific purposes.

PMID- 22984100
TI  - A cephalometric investigation of horizontal lip position in adult Nigerians.
AB  - OBJECTIVES: The aims of this study were to (1) identify soft tissue cephalometric
      norms for horizontal lip position in an adult Nigerian population; (2) compare
      values for Nigerian males and females; and (3) compare Nigerian norms with
      established norms for Caucasians and other populations. DESIGN: A cross-sectional
      descriptive study. SETTING: Lagos University Teaching Hospital Dental Clinic, Idi
      araba, Lagos, Nigeria. PARTICIPANTS: One hundred students (44 males and 56
      females) of the College of Medicine, University of Lagos, aged 18-25 years, of
      Nigerian ancestry, with a normal class I occlusion and no facial asymmetry.
      METHODOLOGY: Lateral cephalometric radiographs of the subjects were taken in
      natural head position. Radiographs were manually traced and 11 soft tissue
      cephalometric parameters measured. These were derived from the Steiner, Ricketts,
      Burstone, Merrifield and Holdaway soft tissue analyses. Male and female values
      were compared using Student's t-test with a level of significance at P<0.05.
      RESULTS: Statistically significant differences were observed between Nigerian
      males and females in eight of the variables studied, with males having more
      protrusive upper and lower lips than the females. Variables, which did not vary
      by sex, were soft tissue facial angle, nose prominence and soft tissue chin
      thickness. In addition, Nigerian norms were higher than norms reported by
      Steiner, Ricketts, Burstone and Holdaway for Caucasian populations, while the Z
      angle was lower than the norm established by Merrifield. CONCLUSIONS: Gender
      specific soft tissue norms for horizontal lip position should be used for
      orthodontic treatment planning in Nigerian subjects. Nigerians have more
      protrusive upper and lower lips compared to Caucasians.

PMID- 22984101
TI  - Digital analysis of staining properties of clear aesthetic brackets.
AB  - OBJECTIVE: To analyse the staining properties of clear orthodontic brackets using
      a digital analysis. DESIGN: In vitro, laboratory study MATERIAL AND METHODS: A
      total of 500 tooth-coloured brackets from 10 brands (five ceramic and five
      plastic) were investigated. The cumulative discolouring effect of staining agents
      (tea, coffee, curry and red wine) were analysed at two consumption levels: light
      and heavy, based on a 6-month period of exposure. Study group brackets were
      immersed in the agents consecutively at 37 degrees C. The control group was only
      exposed to artificial saliva. Samples were analysed digitally to obtain L*, a*
      and b* (lightness, red-green and yellow-blue) colour readings. Using these
      values, total colour change (DeltaE*) at each level was also calculated. Three
      way analysis of variance (ANOVA) test was used for statistical comparisons.
      RESULTS: L* and b* colour parameters showed significant differences (P<0.001)
      between different bracket groups, consumption levels and the type of exposure.
      However, the a* value only differed between bracket groups (P<0.001). According
      to the DeltaE* values, ceramic brackets had less colour change than plastic
      brackets at the end of phase 1 for both the study and control groups. However, as
      consumption time increased, the rate of colour change decreased for the plastic
      brackets. In general, ceramic brackets demonstrated much more resistance to
      staining agents than plastic brackets. CONCLUSIONS: Both plastic and ceramic
      brackets showed changes in colour when exposed to heavy consumption of staining
      agents, with plastic brackets being the most affected.

PMID- 22984102
TI  - Is early Class III protraction facemask treatment effective? A multicentre,
      randomized, controlled trial: 3-year follow-up.
AB  - OBJECTIVE: To investigate the effectiveness of early class III protraction
      facemask treatment in children under 10 years of age at 3-year follow-up. DESIGN:
      Multicentre randomized controlled trial. SUBJECTS AND METHODS: Seventy-three
      patients were randomly allocated, stratified for gender, into early class III
      protraction facemask group (PFG) (n = 35) and a control/no treatment group (CG)
      (n = 38). OUTCOMES: Dentofacial changes were assessed from lateral cephalograms
      and occlusal changes using the peer assessment rating (PAR). Self-esteem was
      assessed using the Piers-Harris children's self-concept scale, and the
      psychosocial impact of malocclusion with oral aesthetic subjective impact score
      (OASIS) questionnaire. Temporomandibular joint (TMJ) signs and symptoms were also
      recorded. The time points for data collection were at registration (DC1), 15
      months later (DC2) and 3 years post-registration (DC3). RESULTS: The following
      mean skeletal and occlusal changes occurred from the class III starting point to
      DC3 (3-year follow-up): SNA, PFG moved forwards +2.3 degrees  (CG forward +1.6
      degrees ; P = 0.14); SNB, PFG moved forwards +0.8 degrees  (CG forward +1.5
      degrees , P = 0.26); ANB, PFG class III base improved +1.5 degrees  (CG stayed
      about the same at +0.1 degrees ; P = 0.001). This contributed to an overall
      difference in ANB between PFG and CG of +1.4 degrees  in favour of early
      protraction facemask treatment. The overjet was still improved by +3.6 mm in the
      PFG and changed a small amount +1.1 mm in the CG (P = 0.001). A 21% improvement
      in PAR was shown in the PFG and the CG worsened by 8.4% (P = 0.02). There was no
      increase in self-esteem (Piers-Harris score) for PFG compared with the CG (P =
      0.56) and no statistically significant difference in the impact of malocclusion
      (OASIS) between groups in terms of the changes from DC1 to DC3 (P = 0.18). TMJ
      signs and symptoms were very low at DC1 and DC3. CONCLUSIONS: The favourable
      effect of early class III protraction facemask treatment undertaken in patients
      under 10 years of age, is maintained at 3-year follow-up in terms of ANB, overjet
      and % PAR improvement. The direct protraction treatment effect at SNA is still
      favourable although not statistically significantly better than the CG. Seventy
      per cent of patients in PFG had maintained a positive overjet which we have
      defined as ongoing treatment success. Early protraction facemask treatment does
      not seem to influence self-esteem or reduce the patient's personal impact of
      their malocclusion at 3-year follow-up.

PMID- 22984103
TI  - What you need to know about bisphosphonates: an overview and general
      recommendations for orthodontic treatment.
AB  - The orthodontic treatment of patients on bisphosphonates is becoming an
      increasing aspect of contemporary practice. This article will draw attention to
      the chemical structure and effects of these drugs on bone and will provide the
      latest recommendations to avoid potential sequelae.

PMID- 22984104
TI  - The William Houston Gold Medal of the Royal College of Surgeons of Edinburgh
      2010.
AB  - This paper describes the clinical orthodontic treatment of two cases treated by
      the recipient of the 2010 Membership in Orthodontics William Houston Gold Medal
      of the Royal College of Surgeons of Edinburgh. The first case describes a three
      phase treatment approach to correct a class II division 2 malocclusion on a non
      extraction basis. The second case describes the treatment of a class III
      malocclusion with a notable unilateral crossbite using a quad-helix, a single
      premolar extraction and upper and lower pre-adjusted fixed appliances.

PMID- 22984105
TI  - Treatment time and occlusal outcome of orthognathic therapy in the East of
      England region.
AB  - OBJECTIVES: To evaluate the process of combined orthognathic and orthodontic
      care. To identify factors that affect treatment time and percentage Peer
      Assessment Rating (PAR) reduction, and the PAR efficiency factor for such cases.
      DESIGN AND SETTING: Retrospective multi centre study of patients who underwent
      orthognathic treatment in the East of England region. METHODS: Analysis of
      consecutive cases that underwent orthognathic surgery in 2008. Inclusion criteria
      included pre- and post-surgery orthodontic treatment. RESULTS: Ten orthodontic
      units submitted data for a total of 118 patients. Within the sample, 64% were
      class III, 35% class II/1 and 1% class II/2. Overall extraction rate, excluding
      third molars, was 58%. Median age at bond up was 17 years. Mean total number of
      orthodontic attendances was 23. Median length of pre-surgical orthodontics was 23
      months and post-surgical orthodontics was 7 months. Median length of total
      treatment was 29 months. Mean wait for surgery was 3.6 months. Diagnosis of
      incisor relationship and skeletal base, transfer of operator, total number of
      visits, tooth extraction and treatment unit affected treatment duration. Median
      pre- and post-treatment PAR scores were 43 and 4, respectively. Median change in
      PAR score was 38.5. Median per cent reduction in PAR was 90.6%. The median PAR
      efficiency factor (reduction in PAR score divided by treatment time in months)
      was 1.24. Diagnosis of incisor relationship and skeletal base correlated with
      percentage reduction in PAR score. CONCLUSIONS: Combined orthognathic treatment
      was effective. Factors affecting treatment duration and percentage reduction in
      PAR have been established.

PMID- 22984106
TI  - Skeletal Class III and anterior open bite treatment with different retention
      protocols: a report of three cases.
AB  - The treatment of skeletal class III and anterior open bite can be unstable and
      orthodontists frequently observe relapse. Here, we report on the management of
      three patients with skeletal class III profiles and open bites treated by
      orthodontic camouflage. Each received a retention protocol involving the use of
      two separate appliances during the night and day accompanied by myofunctional
      therapy. Long-term follow-up revealed a stable outcome.

PMID- 22984110
TI  - Risperidone/paliperidone induced neutropenia and lymphopenia.

PMID- 22984111
TI  - Prevalence, correlates and comorbidity of DSM-IV Cannabis Use and Cannabis Use
      Disorders in Australia.
AB  - OBJECTIVE: To report nationally representative findings on the prevalence,
      correlates, psychiatric comorbidity and treatment of DSM-IV Cannabis Use and
      Cannabis Use Disorders in Australia. METHOD: The 2007 National Survey of Mental
      Health and Wellbeing was a nationally representative household survey of 8841
      Australians (16-85 years) that assessed symptoms of the most prevalent DSM-IV
      mental disorders. RESULTS: Prevalence of lifetime and 12-month cannabis use was
      18% and 6%; prevalence of lifetime and 12-month cannabis use disorder was 6% and
      1%. The conditional prevalence (proportion of ever users who met criteria for a
      disorder) of lifetime and 12-month cannabis use disorder was 32.2% and 14.3%.
      Current cannabis use disorders were more common in males (OR 2.0) and younger
      users (OR 4.6). Strong associations were observed between current cannabis use
      disorders and alcohol use disorders (OR 3.6) and current affective disorders (OR
      3.0). Only 36.2% of those with current cannabis use disorders sought any
      treatment. CONCLUSIONS: The prevalence of cannabis use disorders in the
      Australian population is comparable with that in the USA. Current cannabis use
      disorders are highly concentrated in young Australians who have high levels of
      comorbidity. The low rates of treatment seeking warrant attention in treatment
      and prevention strategies.

PMID- 22984112
TI  - Management of psychogenic polydipsia and hyponatremia in an acute mental health
      unit.

PMID- 22984113
TI  - High levels of immunoglobulin E autoantibody to 14-3-3 epsilon protein correlate
      with protection against severe Plasmodium falciparum malaria.
AB  - Plasmodium falciparum infection generally induces elevated total plasma levels of
      immunoglobulins, some of which recognize self- or parasite-specific antigens. To
      our knowledge, we are the first to report high levels of functional
      immunoglobulin E (IgE) autoantibodies recognizing brain 14-3-3 protein epsilon in
      asymptomatic P. falciparum malaria. 14-3-3 epsilon protein belongs to a family of
      proteins that binds to CD81, a member of the tetraspanin superfamily elicited in
      hepatocyte invasion by sporozoites. Levels of expression of 14-3-3 epsilon
      protein were found to be increased in vivo and in vitro during Plasmodium yoelii
      and P. falciparum intrahepatic development. Collectively, these results indicate
      that self-reactive IgE is produced during malaria. In addition, the negative
      correlation between levels of self-reactive IgE to 14-3-3 epsilon protein and
      parasitemia in asymptomatic malaria due to P. falciparum supports a role for
      these IgE molecules in defense mechanisms, probably by interfering with
      development of liver-stage parasites through the CD81 pathway.

PMID- 22984114
TI  - Crohn's disease susceptibility genes are associated with leprosy in the
      Vietnamese population.
AB  - A genomewide association study in Chinese patients with leprosy detected
      association signals in 16 single-nucleotide polymorphisms (SNPs) belonging to 6
      loci, of which 4 are related to the NOD2 signaling pathway and are Crohn's
      disease susceptibility loci. Here, we studied these 16 SNPs as potential leprosy
      susceptibility factors in 474 Vietnamese leprosy simplex families. We replicated
      SNPs at HLA-DR-DQ, RIPK2, CCDC122-LACC1, and NOD2 as leprosy susceptibility
      factors in Vietnam. These results validated the striking overlap in the genetic
      control of Crohn's disease and leprosy.

PMID- 22984116
TI  - Pregnancy modifies the antibody response to trivalent influenza immunization.
AB  - We report the immunogenicity of trivalent influenza immunization in 29 pregnant
      women compared with 22 nonpregnant women. We obtained blood specimens on day 0
      prior to 2011-2012 influenza vaccine administration and day 28 after
      immunization. Hemagglutination inhibition (HAI) geometric mean titers were
      similar before immunization but were significantly reduced by 40%-50% in pregnant
      women after immunization for influenza A/California(H1N1) (P = .027) and
      A/Perth(H3N2) (P = .037). Postimmunization HAI titers were similar between groups
      for influenza B/Brisbane (P = .390). The geometric mean ratio (fold increase) for
      influenza A(H1N1) was nonsignificantly reduced in pregnant participants (P =
      .089). The percentages of participants who seroconverted and achieved
      seroprotection were similar between groups.

PMID- 22984115
TI  - Dynamic population changes in Mycobacterium tuberculosis during acquisition and
      fixation of drug resistance in patients.
AB  - BACKGROUND: Drug-resistant tuberculosis poses a growing challenge to global
      public health. However, the diversity and dynamics of the bacterial population
      during acquisition of drug resistance have yet to be carefully examined. METHODS:
      Whole-genome sequencing was performed on 7 serial Mycobacterium tuberculosis (M.
      tuberculosis) populations from 3 patients during different stages in the
      development of drug resistance. The population diversity was assessed by the
      number and frequencies of unfixed mutations in each sample. RESULTS: For each
      bacterial population, 8-41 unfixed mutations were monitored by the fraction of
      single-nucleotide polymorphisms at specific loci. Among them, as many as 4 to 5
      resistance-conferring mutations were transiently detected in the same single
      sputum, but ultimately only a single type of mutant was fixed. In addition, we
      identified 14 potential compensatory mutations that occurred during or after the
      emergence of resistance-conferring mutations. CONCLUSIONS: M. tuberculosis
      population within patients exhibited considerable genetic diversity, which
      underwent selections for most fit resistant mutant. These findings have important
      implications and emphasize the need for early diagnosis of tuberculosis to
      decrease the chance of evolving highly fit drug-resistant strains.

PMID- 22984117
TI  - The surprising diversity of Mycobacterium tuberculosis: change you can believe
      in.

PMID- 22984118
TI  - Influenza and malaria coinfection among young children in western Kenya, 2009
      2011.
AB  - BACKGROUND: Although children <5 years old in sub-Saharan Africa are vulnerable
      to both malaria and influenza, little is known about coinfection. METHODS: This
      retrospective, cross-sectional study in rural western Kenya examined outpatient
      visits and hospitalizations associated with febrile acute respiratory illness
      (ARI) during a 2-year period (July 2009-June 2011) in children <5 years old.
      RESULTS: Across sites, 45% (149/331) of influenza-positive patients were
      coinfected with malaria, whereas only 6% (149/2408) of malaria-positive patients
      were coinfected with influenza. Depending on age, coinfection was present in 4%
      8% of outpatient visits and 1%-3% of inpatient admissions for febrile ARI.
      Children with influenza were less likely than those without to have malaria (risk
      ratio [RR], 0.57-0.76 across sites and ages), and children with malaria were less
      likely than those without to have influenza (RR, 0.36-0.63). Among coinfected
      children aged 24-59 months, hospital length of stay was 2.7 and 2.8 days longer
      than influenza-only-infected children at the 2 sites, and 1.3 and 3.1 days longer
      than those with malaria only (all P < .01). CONCLUSIONS: Coinfection with malaria
      and influenza was uncommon but associated with longer hospitalization than single
      infections among children 24-59 months of age.

PMID- 22984119
TI  - Deficient Candida-specific T-helper 17 response during sepsis.
AB  - Patients with sepsis in the intensive care unit (ICU) are prone to develop
      Candida infections. Here, we investigated Candida-induced T-helper 17 (Th17)
      responses during experimental human endotoxemia and in patients with sepsis
      admitted to the ICU. Peripheral blood mononuclear cells were stimulated with
      Candida albicans. The Th17 response was significantly lower during endotoxemia,
      compared with baseline. Patients with gram-negative sepsis had a significantly
      lower Th17 response as compared to healthy controls. These data demonstrate that
      the Th17 response is deficient during endotoxin-related systemic inflammation,
      which likely represents an important risk factor for increased susceptibility to
      develop Candida infection in patients with sepsis.

PMID- 22984120
TI  - The nonsteroidal antiinflammatory drug diclofenac potentiates the in vivo
      activity of caspofungin against Candida albicans biofilms.
AB  - In this study, we demonstrated that in vitro Candida albicans biofilms grown in
      the presence of diclofenac showed increased susceptibility to caspofungin. These
      findings were further confirmed using a catheter-associated biofilm model in
      rats. C. albicans-inoculated catheters retrieved from rats that were treated with
      both diclofenac and caspofungin contained significantly fewer biofilm cells and
      showed no visible biofilms inside the catheter lumens, as documented by scanning
      electron microscopy, as compared to catheters retrieved from rats receiving only
      caspofungin or diclofenac. This report indicates that diclofenac could be useful
      in combination therapy with caspofungin to treat C. albicans biofilm-associated
      infections.

PMID- 22984121
TI  - Overexpression of the Per2 gene in male patients with acute Q fever.
AB  - The prevalence of Q fever is higher in men than in women. Because the expression
      of circadian clock genes differs in male and female mice infected with Coxiella
      burnetii, we hypothesized that circadian genes are differently modulated in men
      and women with Q fever. The expression of the Per2 gene was significantly (P =
      .01) increased in males with acute Q fever compared with healthy volunteers. No
      significant difference was observed in females. We showed for the first time that
      gender altered the expression of a circadian gene, Per2, in an infectious
      disease.

PMID- 22984122
TI  - Acclimation of leaf nitrogen to vertical light gradient at anthesis in wheat is a
      whole-plant process that scales with the size of the canopy.
AB  - Vertical leaf nitrogen (N) gradient within a canopy is classically considered as
      a key adaptation to the local light environment that would tend to maximize
      canopy photosynthesis. We studied the vertical leaf N gradient with respect to
      the light gradient for wheat (Triticum aestivum) canopies with the aims of
      quantifying its modulation by crop N status and genetic variability and analyzing
      its ecophysiological determinants. The vertical distribution of leaf N and light
      was analyzed at anthesis for 16 cultivars grown in the field in two consecutive
      seasons under two levels of N. The N extinction coefficient with respect to light
      (b) varied with N supply and cultivar. Interestingly, a scaling relationship was
      observed between b and the size of the canopy for all the cultivars in the
      different environmental conditions. The scaling coefficient of the b-green area
      index relationship differed among cultivars, suggesting that cultivars could be
      more or less adapted to low-productivity environments. We conclude that the
      acclimation of the leaf N gradient to the light gradient is a whole-plant process
      that depends on canopy size. This study demonstrates that modeling leaf N
      distribution and canopy expansion based on the assumption that leaf N
      distribution parallels that of the light is inappropriate. We provide a robust
      relationship accounting for vertical leaf N gradient with respect to vertical
      light gradient as a function of canopy size.

PMID- 22984123
TI  - Predictive modeling of biomass component tradeoffs in Brassica napus developing
      oilseeds based on in silico manipulation of storage metabolism.
AB  - Seed oil content is a key agronomical trait, while the control of carbon
      allocation into different seed storage compounds is still poorly understood and
      hard to manipulate. Using bna572, a large-scale model of cellular metabolism in
      developing embryos of rapeseed (Brassica napus) oilseeds, we present an in silico
      approach for the analysis of carbon allocation into seed storage products.
      Optimal metabolic flux states were obtained by flux variability analysis based on
      minimization of the uptakes of substrates in the natural environment of the
      embryo. For a typical embryo biomass composition, flux sensitivities to changes
      in different storage components were derived. Upper and lower flux bounds of each
      reaction were categorized as oil or protein responsive. Among the most oil
      responsive reactions were glycolytic reactions, while reactions related to
      mitochondrial ATP production were most protein responsive. To assess different
      biomass compositions, a tradeoff between the fractions of oil and protein was
      simulated. Based on flux-bound discontinuities and shadow prices along the
      tradeoff, three main metabolic phases with distinct pathway usage were
      identified. Transitions between the phases can be related to changing modes of
      the tricarboxylic acid cycle, reorganizing the usage of organic carbon and
      nitrogen sources for protein synthesis and acetyl-coenzyme A for cytosol
      localized fatty acid elongation. The phase close to equal oil and protein
      fractions included an unexpected pathway bypassing alpha-ketoglutarate-oxidizing
      steps in the tricarboxylic acid cycle. The in vivo relevance of the findings is
      discussed based on literature on seed storage metabolism.

PMID- 22984124
TI  - Impact of the absence of stem-specific beta-glucosidases on lignin and
      monolignols.
AB  - Monolignol glucosides are thought to be implicated in the lignin biosynthesis
      pathway as storage and/or transportation forms of cinnamyl alcohols between the
      cytosol and the lignifying cell walls. The hydrolysis of these monolignol
      glucosides would involve beta-glucosidase activities. In Arabidopsis (Arabidopsis
      thaliana), in vitro studies have shown the affinity of beta-GLUCOSIDASE45
      (BGLU45) and BGLU46 for monolignol glucosides. BGLU45 and BGLU46 genes are
      expressed in stems. Immunolocalization experiments showed that BGLU45 and BGLU46
      proteins are mainly located in the interfascicular fibers and in the protoxylem,
      respectively. Knockout mutants for BGLU45 or BGLU46 do not have a lignin
      deficient phenotype. Coniferin and syringin could be detected by ultra
      performance liquid chromatography-mass spectrometry in Arabidopsis stems. Stems
      from BGLU45 and BGLU46 mutant lines displayed a significant increase in coniferin
      content without any change in coniferyl alcohol, whereas no change in syringin
      content was observed. Other glucosylated compounds of the phenylpropanoid pathway
      were also deregulated in these mutants, but to a lower extent. By contrast,
      BGLU47, which is closely related to BGLU45 and BGLU46, is not implicated in
      either the general phenylpropanoid pathway or in the lignification of stems and
      roots. These results confirm that the major in vivo substrate of BGLU45 and
      BGLU46 is coniferin and suggest that monolignol glucosides are the storage form
      of monolignols in Arabidopsis, but not the direct precursors of lignin.

PMID- 22984125
TI  - Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B
      cell lymphomas in the era of rituximab.
AB  - OBJECTIVE: The incorporation of rituximab in immunochemotherapy has improved
      treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some
      diffuse large B-cell lymphomas remains dismal. Identification of adverse
      prognostic subgroups is essential for the choice of appropriate therapeutic
      strategy. METHODS: We retrospectively investigated the impact of so-called
      'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving
      c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving
      BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B
      cell lymphoma patients. RESULTS: According to the revised international
      prognostic index, no patients were cytogenetically diagnosed with double-hit
      lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of
      33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit
      lymphoma patients possessed both nodal and extranodal involvement. The overall
      complete response rate was 89.3%, overall survival 87.1% and progression-free
      survival 75.8% over 2 years (median observation period: 644 days). The complete
      response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for
      the double-hit lymphoma patients. Significantly longer progression-free survival
      and overall survival were observed for the 'very good' and the 'good' risk
      patients than for the 'poor' risk patients. Moreover, the progression-free
      survival of double-hit lymphoma was significantly shorter than that of the non
      double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall
      survival of the double-hit lymphoma patients also tended to be shorter than that
      of the non-double-hit lymphoma 'poor' risk group. CONCLUSIONS: The diagnosis of
      double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse
      large B-cell lymphomas and indicate the need for the development of novel
      therapeutic strategies for double-hit lymphoma.

PMID- 22984127
TI  - Subpectoral biceps tenodesis: an anatomic study and evaluation of at-risk
      structures.
AB  - BACKGROUND: The neurovascular structures of the proximal arm may be at risk for
      iatrogenic injury during open subpectoral biceps tenodesis (OSPBT). PURPOSE: To
      define the anatomic relationships and at-risk structures during OSPBT and to
      quantify the effect of arm rotation on the position of the musculocutaneous
      nerve. STUDY DESIGN: Descriptive laboratory study. METHODS: The OSPBT approach
      was performed in 17 unembalmed cadaveric upper extremities. The tenodesis site
      was inferior to the bicipital groove and positioned so the musculotendinous
      portion of the long head of the biceps rested at the inferior border of the
      pectoralis major. A meticulous dissection identified the brachial artery, deep
      brachial artery, cephalic vein, brachial vein, medial brachial cutaneous nerve,
      medial antebrachial cutaneous nerve, intercostal brachial cutaneous nerve,
      musculocutaneous nerve, axillary nerve, median nerve, and radial nerve.
      Superficial structures were measured from the superior and inferior aspects of
      the incision, and deep structures were measured from the tenodesis site and
      nearest retractor. The musculocutaneous nerve was measured with the arm in
      neutral, internal, and external rotation. RESULTS: The musculocutaneous nerve was
      10.1 mm (range, 6-18 mm) medial to the tenodesis location and 2.9 mm (range, 1-6
      mm) medial to the medially placed retractor in neutral arm position. The radial
      nerve and deep brachial artery were 7.4 mm (range, 2-12 mm) and 5.7 mm (range, 1
      10 mm) deep to the medially placed retractor, respectively. With the arm
      internally rotated to 45 degrees , the musculocutaneous nerve was 8.1 mm from the
      tenodesis site, compared with 19.4 mm with the arm 45 degrees  externally rotated
      (P = .009). The median nerve, brachial artery, and brachial vein were >2.5 cm
      from the tenodesis site and nearest retractor during deep dissection. CONCLUSION:
      The musculocutaneous nerve, radial nerve, and deep brachial artery are within 1
      cm of the standard medial retractor. External rotation of the arm moves the
      musculocutaneous nerve 11.3 mm further away from the tenodesis site compared with
      the internally rotated position. CLINICAL RELEVANCE: The musculocutaneous nerve,
      radial nerve, and deep brachial artery course in close proximity to the operative
      field and are therefore at risk during OSPBT. Limiting the use of medial
      retraction and placement of the arm in an externally rotated position will
      minimize neurovascular injury.

PMID- 22984126
TI  - Successful treatment of Hurthle cell thyroid carcinoma with lung and liver
      metastasis using docetaxel and cisplatin.
AB  - A 36-year-old man was found to have Hurthle cell carcinoma, as diagnosed with
      surgical pathology after a lobectomy of the thyroid. A post-operative magnetic
      resonance imaging scan revealed a small mass in the lower pole of the right
      thyroid and a computed tomography scan showed bilateral nodules in the lungs and
      the neck, and multi-focal disease in the liver. He was treated with a docetaxel
      and cisplatin chemotherapy regimen. After six cycles of the docetaxel and
      cisplatin regimen, we could hardly find the lesions in the lungs and the liver,
      and the patient presented a complete tumor response lasting 17 months and has not
      shown any tumor recurrence till now. The docetaxel and cisplatin regimen may be
      an effective chemotherapy regimen for multi-metastases of Hurthle cell cancer.

PMID- 22984128
TI  - No differences in prevalence of osteoarthritis or function after open versus
      endoscopic technique for anterior cruciate ligament reconstruction: 12-year
      follow-up report of a randomized controlled trial.
AB  - BACKGROUND: Although arthroscopic techniques are the most common procedures today
      when reconstructing the anterior cruciate ligament (ACL), many surgeons still
      prefer the open and/or 2-incision techniques. HYPOTHESIS: There are no
      differences in knee function or prevalence of knee osteoarthritis (OA) in
      patients who have undergone the open versus endoscopic technique for ACL
      reconstruction using the patellar tendon autograft. STUDY DESIGN: Randomized
      controlled trial; Level of evidence, 2. METHODS: Sixty-seven patients with
      subacute or chronic rupture of the ACL were randomly assigned to open (OPEN) (n =
      33) or endoscopic (ENDO) (n = 34) reconstruction. Function was evaluated by the
      Cincinnati knee score, single-legged hop tests, and isokinetic muscle strength
      tests. The radiographs were classified according to the Kellgren and Lawrence
      (KL) classification system, defining grade 2 or more as the cutoff point for knee
      OA. The Insall-Salvati ratio and the Blackburne-Peel ratio were used to calculate
      the patellar position and height. RESULTS: Mean age at inclusion and at the 12
      year follow-up evaluation was 27.9 +/- 8.6 and 39.8 +/- 8.6 years, respectively.
      At 12-year follow-up, 53 patients (79%) were eligible for evaluation. There were
      no significant differences between the 2 surgical procedures with respect to the
      pain, function, muscle strength, hop tests, patellar height, or the prevalence of
      OA. The prevalence of OA was high in the tibiofemoral joint on the operated side,
      79% and 80% in the OPEN and ENDO groups, respectively. For the uninvolved knee,
      the corresponding numbers were 36% and 21%. CONCLUSION: This study suggests that
      the open procedure does not produce more functional problems or osteoarthritis
      compared with the endoscopic technique up to 12 years postoperatively.

PMID- 22984129
TI  - Restoration of shoulder biomechanics according to degree of repair completion in
      a cadaveric model of massive rotator cuff tear: importance of margin convergence
      and posterior cuff fixation.
AB  - BACKGROUND: Complete repair in massive rotator cuff tear may not be possible,
      allowing for only partial repair. However, the effect of partial repair on
      glenohumeral biomechanics has not been evaluated. Therefore, the purpose of this
      study was to compare the rotational range of motion (ROM), glenohumeral
      kinematics, and gap formation at the repaired tendon edge following massive cuff
      tear and repair according to the degree of repair completion. HYPOTHESIS:
      Posterior fixation will restore the altered biomechanics of massive rotator cuff
      tear. STUDY DESIGN: Controlled laboratory study. METHODS: Eight cadaveric
      shoulders were tested at 0 degrees , 30 degrees , and 60 degrees  of abduction in
      the scapular plane. Muscle loading was applied based on physiological muscle
      cross-sectional area ratios. Maximum internal (MaxIR) and external rotations
      (MaxER) were measured. Humeral head apex (HHA) position and gap formation at the
      repaired tendon edge were measured using a MicroScribe from MaxIR to MaxER in 30
      degrees  increments. Testing was performed for intact, massive cuff tear,
      complete repair, and 4 types of partial repair. A repeated-measures analysis of
      variance was used to determine significant differences. RESULTS: Massive tear
      significantly increased ROM and shifted HHA superiorly in MaxIR at all abduction
      angles (P < .05). The complete repair restored ROM to intact (P < .05), while all
      partial repairs did not. Abnormal HHA elevation due to massive tear was restored
      by all repairs (P < .05). Release of the anterior single row alone and release of
      the marginal convergence significantly increased gap formation at the anterior
      tendon edge (P < .05). CONCLUSION: This study emphasizes the importance of
      anterior fixation in massive cuff tear to restore rotational range of motion and
      decrease gap formation at the repaired tendon edge and of posterior fixation to
      restore abnormal glenohumeral kinematics due to massive cuff tear. CLINICAL
      RELEVANCE: If complete repair of massive cuff tear is not possible, posterior
      cuff (infraspinatus) repair is necessary to restore abnormal glenohumeral
      kinematics, and margin convergence anteriorly is recommended to decrease gap
      formation of the repaired tendon edge, which may provide a better biomechanical
      environment for healing.

PMID- 22984130
TI  - Remplissage repair--new frontiers in the prevention of recurrent shoulder
      instability: a 2-year follow-up comparative study.
AB  - BACKGROUND: An engaging Hill-Sachs lesion is a defect of the humeral head, large
      enough to cause locking of the humeral head against the anterior corner of the
      glenoid rim when the arm is at 90 degrees  of abduction and more than 30 degrees 
      of external rotation. HYPOTHESIS: When Bankart lesions are associated with
      engaging Hill-Sachs defects, simultaneous Bankart repair and remplissage provide
      lower recurrence rates than does Bankart repair alone. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: Fifty patients (36 men, 14 women) with
      combined engaging Hill-Sachs and Bankart lesions were evaluated, before and after
      arthroscopic management, at a minimum follow-up of 2 years. After imaging and
      arthroscopic assessment, 25 patients underwent remplissage and Bankart repair,
      and 25 patients received Bankart repair alone. Patients were evaluated using the
      UCLA, Constant, and Rowe scores, and range of motion was measured using a
      goniometer. Postoperatively, all patients underwent magnetic resonance imaging to
      assess the status of healing of the anterior labrum and whether the tenodesis of
      the infraspinatus covered the Hill-Sachs defect. RESULTS: At the last
      appointment, active forward elevation, external rotation beside the body,
      internal rotation, and all administered scores were significantly improved
      compared with baseline assessment, with no statistically significant intergroup
      differences. A new posttraumatic dislocation occurred in 5 patients, all from the
      Bankart-only group (20%). CONCLUSION: Remplissage is a safe, relatively short
      procedure that allows the surgeon to address large humeral defects with a low
      postoperative recurrence rate. Humeral head large defects predispose to recurrent
      instability of the shoulder and deserve surgical management.

PMID- 22984131
TI  - Effects of demineralized bone matrix on tendon-bone healing in an intra-articular
      rodent model.
AB  - BACKGROUND: Techniques to improve and accelerate tendon-bone healing could be
      advantageous in anterior cruciate ligament (ACL) reconstruction. Effects of
      demineralized bone matrix (DBM) on intra-articular tendon-bone healing have not
      been examined. HYPOTHESIS: Demineralized bone matrix has the potential to convey
      osteoinductive growth proteins to the site of healing at the tendon-bone
      interface. We hypothesized that the presence of DBM will result in more bone
      formation and hasten tendon-bone healing. STUDY DESIGN: Controlled laboratory
      study. METHODS: Fifty-six female athymic rnu/rnu (nude) rats were used. Rats were
      randomly allocated into 2 groups (control or treatment). The control group
      underwent an ACL reconstruction, while the treatment group had human DBM
      implanted in the tendon graft and bone tunnel before reconstruction. Rats were
      sacrificed at 2 (n = 8), 4 (n = 24), and 6 (n = 24) weeks for histological, and
      immunohistochemical (t = 2, 4, and 6 weeks), and biomechanical testing and micro
      computed tomography (t = 4 and 6 weeks) end points. RESULTS: Our findings suggest
      that in the presence of DBM, tendon-bone healing is augmented by increased woven
      bone formation and enhanced bone remodeling as indicated by histology and micro
      computed tomography. This ultimately resulted in a statistically significant
      increase in peak load to failure of the tendon-bone interface at 4 weeks (DBM
      group: 5.96 +/- 1.36 N; control group: 2.86 +/- 0.7 N) and 6 weeks (DBM group:
      9.13 +/- 0.97 N; control group: 5.81 +/- 1.1 N). CONCLUSION: Demineralized bone
      matrix at the tendon-bone interface promotes healing between the tendon and bone
      in a rodent ACL model. CLINICAL RELEVANCE: Introduction of osteoinductive DBM at
      the tendon-bone interface during ACL reconstructive surgery may improve short
      term outcomes.

PMID- 22984132
TI  - What affects Clean Delivery Kit utilization at birth in Nepal? A qualitative
      study.
AB  - BACKGROUND: Infection is one of the biggest causes of maternal and neonatal death
      in low-income countries. Clean Delivery Kits (CDKs) promote clean delivery and
      neonatal care. Our qualitative research explores reasons for low CDK utilization,
      and describes community perceptions of CDKs in Nepal. METHODS: We conducted 18
      focus group discussions and 40 interviews with CDK users and nonusers, service
      providers, birth attendants, and household decision makers in 6 districts. We
      also conducted interviews with central level personnel. CDK users were aware of
      its benefits, and utilization was largely compatible with birth practices.
      Utilization was prevented by lack of awareness about the benefits and lack of
      availability. Participants believed that CDKs were for home use. CONCLUSION: Poor
      promotion of CDK is related to the disjuncture of promoting CDK use, while
      encouraging institutional deliveries. If CDKs are made available and marketed for
      use in households and health institutions, utilization may increase.

PMID- 22984133
TI  - Sexual and reproductive health of micronesians: a systematic review of the
      literature.
AB  - INTRODUCTION: Recent evidence of negative sexual and reproductive health (SRH)
      outcomes for Micronesian migrants warrants a review of what is currently known
      about Micronesian SRH beliefs, customs, behaviors, outcomes, and access to SRH
      services. METHODS: A systematic literature review employing the matrix method was
      conducted using the same key terms for 8 databases. Peer-reviewed articles
      published between 1990 and 2010 were abstracted for several key components,
      including topics, methodology, and other important elements necessary to assess
      major findings, strengths, and weaknesses. RESULTS: Thirty-two articles matched
      the inclusion criteria for review. Of these articles, the major research of
      interest was behavior relating to sexual risk behavior, pregnancy, health care
      seeking, and HIV/AIDS for various populations throughout Micronesia. Study
      populations ranged from pregnant women seeking prenatal care to students in high
      school. CONCLUSION: No cohesive body of SRH literature exists for one topic or
      one community within Micronesia to date.

PMID- 22984134
TI  - Factors affecting IUCD discontinuation in Nepal: a nested case-control study.
AB  - Information related to contraception discontinuation, especially in the context
      of Nepal is very limited. A nested case-control study was carried out to
      determine the factors affecting discontinuation of intrauterine contraceptive
      devices (IUCDs). A total of 115 cases (IUCD discontinuers) and 115 controls (IUCD
      continuers) were randomly selected based on the data obtained from the user's
      record of a family planning center in Kathmandu. Matching criteria were age
      during insertion and date of insertion of IUCD. Logistic regression was used to
      analyze the data. When cases were compared with controls, the results showed that
      place of residence, sex of last child, reproductive intention, experience of side
      effects, and follow-up practice were associated with discontinuation of the IUCD.
      Experience of side effects has been seen as the major reason for discontinuation.
      The results suggest that side effects after IUCD insertion should be properly
      discussed and promptly treated to reduce the discontinuation rate. 

PMID- 22984135
TI  - Sir Marc Armand Ruffer and Giulio Bizzozero: the first reports on efferocytosis.
AB  - Sir Marc Armand Ruffer, a physician and a bacteriologist, well-known for his
      discoveries in paleopathology, and Giulio Bizzozero, an Italian pathologist,
      famous for his work on platelets, have made significant contributions in the
      field of phagocytosis. They both reported among the very first descriptions of
      efferocytosis.

PMID- 22984136
TI  - Tepidimonas fonticaldi sp. nov., a slightly thermophilic betaproteobacterium
      isolated from a hot spring.
AB  - A slightly thermophilic bacterial strain, designated AT-A2(T), was isolated from
      a hot spring water sample taken from the Antun hot spring in Taiwan and
      characterized using a polyphasic taxonomic approach. Cells of strain AT-A2(T)
      were aerobic, Gram-negative, motile by a single polar flagellum and formed non
      pigmented colonies. Growth occurred at 35-60  degrees C (optimum, 55  degrees C),
      with 0-1.0 % NaCl (optimum, 0.2 %) and at pH 7.0-9.0 (optimum, pH 7.0).
      Phylogenetic analyses based on 16S rRNA gene sequences showed that strain AT
      A2(T) belonged to the genus Tepidimonas and its closest neighbour was Tepidimonas
      thermarum AA-1(T) with a sequence similarity of 97.5 %. The predominant cellular
      fatty acids were C16 : 0 (40.2 %), summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c; 20.1 %) and C17 : 0 cyclo (11.5 %). The major respiratory quinone was Q
      8. The polar lipid profile consisted of phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, an uncharacterized aminolipid and
      several uncharacterized phospholipids. The DNA G+C content of strain AT-A2(T) was
      70.1 mol%. The mean level of DNA-DNA relatedness between strain AT-A2(T) and
      Tepidimonas thermarum AA-1(T) was 23.9 %. On the basis of the phylogenetic and
      phenotypic data, strain AT-A2(T) should be classified as representing a novel
      species, for which the name Tepidimonas fonticaldi sp. nov. is proposed. The type
      strain is AT-A2(T) ( = LMG 26746(T) = KCTC 23862(T) = BCRC 80391(T)).

PMID- 22984137
TI  - Magnetovibrio blakemorei gen. nov., sp. nov., a magnetotactic bacterium
      (Alphaproteobacteria: Rhodospirillaceae) isolated from a salt marsh.
AB  - A magnetotactic bacterium, designated strain MV-1(T), was isolated from sulfide
      rich sediments in a salt marsh near Boston, MA, USA. Cells of strain MV-1(T) were
      Gram-negative, and vibrioid to helicoid in morphology. Cells were motile by means
      of a single polar flagellum. The cells appeared to display a transitional state
      between axial and polar magnetotaxis: cells swam in both directions, but
      generally had longer excursions in one direction than the other. Cells possessed
      a single chain of magnetosomes containing truncated hexaoctahedral crystals of
      magnetite, positioned along the long axis of the cell. Strain MV-1(T) was a
      microaerophile that was also capable of anaerobic growth on some nitrogen oxides.
      Salinities greater than 10 % seawater were required for growth. Strain MV-1(T)
      exhibited chemolithoautotrophic growth on thiosulfate and sulfide with oxygen as
      the terminal electron acceptor (microaerobic growth) and on thiosulfate using
      nitrous oxide (N2O) as the terminal electron acceptor (anaerobic growth). Chemo
      organoautotrophic and methylotrophic growth was supported by formate under
      microaerobic conditions. Autotrophic growth occurred via the Calvin-Benson
      Bassham cycle. Chemo-organoheterotrophic growth was supported by various organic
      acids and amino acids, under microaerobic and anaerobic conditions. Optimal
      growth occurred at pH 7.0 and 26-28  degrees C. The genome of strain MV-1(T)
      consisted of a single, circular chromosome, about 3.7 Mb in size, with a G+C
      content of 52.9-53.5 mol%.Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain MV-1(T) belongs to the family Rhodospirillaceae within the
      Alphaproteobacteria, but is not closely related to the genus Magnetospirillum.
      The name Magnetovibrio blakemorei gen. nov., sp. nov. is proposed for strain MV
      1(T). The type strain of Magnetovibrio blakemorei is MV-1(T) ( = ATCC BAA-1436(T)
      = DSM 18854(T)).

PMID- 22984138
TI  - Chromobacterium vaccinii sp. nov., isolated from native and cultivated cranberry
      (Vaccinium macrocarpon Ait.) bogs and irrigation ponds.
AB  - A large number of Gram-negative, motile, mesophilic, violacein-producing bacteria
      were isolated from the soils and roots of Vaccinium macrocarpon Ait. and Kalmia
      angustifolia L. plants and from irrigation ponds associated with wild and
      cultivated cranberry bogs in Massachusetts, USA. Phylogenetic analyses of 16S
      rRNA gene sequences placed these isolates in a clade with Chromobacterium
      species, but the specialized environment from which they were isolated, their low
      genomic DNA relatedness with Chromobacterium violaceum ATCC 12472(T) and C.
      subtsugae PRAA4-1(T), significant differences in fatty acid composition and
      colony morphology indicate that the cranberry and Kalmia isolates comprise a
      separate species of Chromobacterium, for which the name Chromobacterium vaccinii
      sp. nov. is proposed. Strain MWU205(T) ( = ATCC BAA-2314(T)  = DSM 25150(T)) is
      proposed as the type strain for the novel species. Phenotypic analysis of 26
      independent isolates of C. vaccinii sp. nov. indicates that, despite close
      geographical and biological proximity, there is considerable metabolic diversity
      among individuals within the population.

PMID- 22984139
TI  - Methylopila musalis sp. nov., an aerobic, facultatively methylotrophic bacterium
      isolated from banana fruit.
AB  - A newly isolated, facultatively methylotrophic bacterium (strain MUSA(T)) was
      investigated. The isolate was strictly aerobic, Gram-stain-negative,
      asporogenous, motile, rod-shaped and multiplied by binary fission. The strain
      utilized methanol, methylamine and an apparently narrow range of multi-carbon
      compounds, but not methane, dichloromethane or CO2/H2, as the carbon and energy
      sources. Growth occurred at pH 5.5-9.5 (optimum, pH 7.0) and 16-40  degrees C
      (optimum, 28-30  degrees C). The major fatty acids of methanol-grown cells were
      C18 : 1omega7c, C18 : 0 and 11-methyl-C18 : 1omega7c . The predominant
      phospholipids were phosphatidylethanolamine, phosphatidylcholine,
      phosphatidylglycerol and phosphatidylmonomethylethanolamine. The major ubiquinone
      was Q-10. The strain had methanol and methylamine dehydrogenases as well as the
      enzymes of the N-methylglutamate pathway (lyases of gamma-glutamylmethylamide and
      N-methylglutamate). C1 assimilation occurs via the isocitrate lyase-negative
      serine pathway. Ammonium was assimilated by glutamate dehydrogenase and the
      glutamate cycle (glutamate synthase/glutamine synthetase). The DNA G+C content of
      the strain was 64.5 mol% (determined from the melting temperature). Based on 16S
      rRNA gene sequence similarity (97.0-98.9 %) and DNA-DNA relatedness (36-38 %)
      with representatives of the genus Methylopila (Methylopila capsulata IM1(T) and
      Methylopila jiangsuensis JZL-4(T)) the isolate was classified as a novel species
      of the genus Methylopila, for which the name Methylopila musalis sp. nov. is
      proposed. The type strain is MUSA(T) ( = VKM B-2646(T) = DSM 24986(T) = CCUG
      61696(T)).

PMID- 22984140
TI  - Classification of Leptospira genomospecies 1, 3, 4 and 5 as Leptospira alstonii
      sp. nov., Leptospira vanthielii sp. nov., Leptospira terpstrae sp. nov. and
      Leptospira yanagawae sp. nov., respectively.
AB  - The genus Leptospira currently comprises 16 named species. In addition, four
      unnamed hybridization groups were designated Leptospira genomospecies 1, 3, 4 and
      5. These groups represent valid species-level taxa, but were not assigned names
      in the original description by Brenner et al. [Int J Syst Bacteriol 49, 839-858
      (1999)]. To rectify this situation, it is proposed that Leptospira genomospecies
      1, genomospecies 3, genomospecies 4 and genomospecies 5 should be classified as
      Leptospira alstonii sp. nov., Leptospira vanthielii sp. nov., Leptospira
      terpstrae sp. nov. and Leptospira yanagawae sp. nov., respectively, with strains
      L. alstonii 79601(T) ( = ATCC BAA-2439(T)), L. vanthielii WaZ Holland(T) ( = ATCC
      700522(T)), L. terpstrae LT 11-33(T) ( = ATCC 700639(T)) and L. yanagawae Sao
      Paulo(T) ( = ATCC 700523(T)) as the type strains. The type strains are also
      available from the culture collections of the WHO Collaborating Centres in
      Amsterdam, The Netherlands, and Brisbane, Australia.

PMID- 22984141
TI  - Photorhabdus luminescens subsp. noenieputensis subsp. nov., a symbiotic bacterium
      associated with a novel Heterorhabditis species related to Heterorhabditis
      indica.
AB  - The bacterial symbiont AM7(T), isolated from a novel entomopathogenic nematode
      species of the genus Heterorhabditis, displays the main phenotypic traits of the
      genus Photorhabdus and is highly pathogenic to Galleria mellonella. Phylogenetic
      analysis based on a multigene approach (16S rRNA, recA, gyrB, dnaN, gltX and
      infB) confirmed the classification of isolate AM7(T) within the species
      Photorhabdus luminescens and revealed its close relatedness to Photorhabdus
      luminescens subsp. caribbeanensis, P. luminescens subsp. akhurstii and P.
      luminescens subsp. hainanensis. The five concatenated protein-encoding sequences
      (4197 nt) of strain AM7(T) revealed 95.8, 95.4 and 94.9 % nucleotide identity to
      sequences of P. luminescens subsp. caribbeanensis HG29(T), P. luminescens subsp.
      akhurstii FRG04(T) and P. luminescens subsp. hainanensis C8404(T), respectively.
      These identity values are less than the threshold of 97 % proposed for
      classification within one of the existing subspecies of P. luminescens. Unlike
      other strains described for P. luminescens, strain AM7(T) produces acid from
      adonitol, sorbitol and xylitol, assimilates xylitol and has no lipase activity on
      medium containing Tween 20 or 60. Strain AM7(T) is differentiated from P.
      luminescens subsp. caribbeanensis by the assimilation of N-acetylglucosamine and
      the absence of haemolytic activity. Unlike P. luminescens subsp. akhurstii,
      strain AM7(T) does not assimilate mannitol, and it is distinguished from P.
      luminescens subsp. hainanensis by the assimilation of trehalose and citrate, the
      inability to produce indole from tryptophan and the presence of acetoin
      production and urease activity. Strain AM7(T) ( = ATCC BAA-2407(T)  = DSM
      25462(T)) belongs to a novel subspecies, and is proposed as the type strain of
      Photorhabdus luminescens subsp. noenieputensis sp. nov.

PMID- 22984142
TI  - The intolerance of uncertainty scale: measurement invariance, population
      heterogeneity, and its relation with worry among self-identifying White and Black
      respondents.
AB  - Although it is understood that assessment tools require evaluation using diverse
      samples, such evaluations are relatively rare. There are obstacles to such work,
      but it remains important to pursue psychometric data in broad samples. As such,
      we evaluated measurement invariance and population heterogeneity of two versions
      of a widely used measure in the anxiety literature--the Intolerance of
      Uncertainty Scale (IUS)--among self-identifying White (N = 1,185) and Black (N =
      301) students. Data from multiple-groups confirmatory factor analysis supported
      the equivalence of the equal form and factor loadings of both IUS versions in
      White and Black respondents. However, specific IUS items functioned differently
      in the two groups, with more IUS items appearing biased in the full-length
      relative to the short-form version. Correlations between IUS factors and worry
      were equivalent among White and Black respondents. We discuss the implications of
      these results for future research.

PMID- 22984143
TI  - Atherogenic low density lipoprotein phenotype in long-term survivors of childhood
      acute lymphoblastic leukemia.
AB  - Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk
      of cardiovascular disease. Small density lipoproteins are atherogenic but have
      not been studied in this population. We conducted a cross-sectional analysis of
      110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense
      LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid
      subfractions were measured using Vertical Auto Profile-II. Participants with
      greater than 50% of LDL-cholesterol (LDL-c) in small dense LDL fractions
      (LDL(3+4)) were classified as LDL pattern B. Visceral and subcutaneous adipose
      tissue (VAT, SAT) volumes were also measured by computed tomography. While the
      mean LDL-c level of ALL survivors was 108.7 +/- 26.8 mg/dl, 36% (40/110) of
      survivors had atherogenic LDL pattern B. This pattern was more common in males
      (26/47; 55%) than in females (14/63; 22%, P = 0.001) and more common in survivors
      treated with cranial radiotherapy (15/33; 45%) than in those who were treated
      with chemotherapy alone (25/77; 33%; P = 0.04, adjusted for age, gender, history
      of hypertension, and smoking history). VAT was associated with atherogenic
      lipids: LDL pattern B and LDL(3+4) levels. This association was independent of
      other measures of body fat. We conclude that a substantial proportion of ALL
      survivors had an atherogenic LDL phenotype despite normal mean LDL-c levels. An
      atherogenic LDL phenotype may contribute to the increase in cardiovascular
      mortality and morbidity in this population.

PMID- 22984144
TI  - Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase
      products in platelet activation.
AB  - Human platelet-type 12-lipoxygenase (12-LOX) has recently been shown to play an
      important role in regulation of human platelet function by reacting with
      arachidonic acid (AA). However, a number of other fatty acids are present on the
      platelet surface that, when cleaved from the phospholipid, can be oxidized by 12
      LOX. We sought to characterize the substrate specificity of 12-LOX against six
      essential fatty acids: AA, dihomo-gamma-linolenic acid (DGLA), eicosapentaenoic
      acid (EPA), alpha-linolenic acid (ALA), eicosadienoic acid (EDA), and linoleic
      acid (LA). Three fatty acids were comparable substrates (AA, DGLA, and EPA), one
      was 5-fold slower (ALA), and two showed no reactivity with 12-LOX (EDA and LA).
      The bioactive lipid products resulting from 12-LOX oxidation of DGLA, 12-(S)
      hydroperoxy-8Z,10E,14Z-eicosatrienoic acid [12(S)-HPETrE], and its reduced
      product, 12(S)-HETrE, resulted in significant attenuation of agonist-mediated
      platelet aggregation, granule secretion, alphaIIbbeta3 activation, Rap1
      activation, and clot retraction. Treatment with DGLA similarly inhibited PAR1
      mediated platelet activation as well as platelet clot retraction. These
      observations are in surprising contrast to our recent work showing 12(S)-HETE is
      a prothrombotic bioactive lipid and support our hypothesis that the overall
      effect of 12-LOX oxidation of fatty acids in the platelet is dependent on the
      fatty acid substrates available at the platelet membrane.

PMID- 22984145
TI  - Hypomorphic sialidase expression decreases serum cholesterol by downregulation of
      VLDL production in mice.
AB  - Lipoprotein metabolism is an important contributing factor in the development and
      progression of atherosclerosis. Plasma lipoproteins and their receptors are
      heavily glycosylated and sialylated, and levels of sialic acids modulate their
      biological functions. Sialylation is controlled by the activities of
      sialyltranferases and sialidases. To address the impact of sialidase (neu1)
      activity on lipoprotein metabolism, we have generated a mouse model with a
      hypomorphic neu1 allele (B6.SM) that displays reduced sialidase expression and
      sialidase activity. The objectives of this study are to determine the impact of
      sialidase on the rate of hepatic lipoprotein secretion and lipoprotein uptake.
      Our results indicate that hepatic levels of cholesterol and triglycerides are
      significantly higher in B6.SM mice compared with C57Bl/6 mice; however, VLDL
      triglyceride production rate is lower. In addition, B6.SM mice show significantly
      lower levels of hepatic microsomal triglyceride transfer protein (MTP) and active
      sterol-regulatory element binding protein (SREBP)-2 but higher levels of
      diglyceride acyltransferase (DGAT)2; these are all indicative of increased
      hepatic lipid storage. Rescue of sialidase activity in hypomorphic sialidase mice
      using helper-dependent adenovirus resulted in increased VLDL production and an
      increase in MTP levels. Furthermore, hypomorphic sialidase expression results in
      stabilization of hepatic LDL receptor (LDLR) protein expression, which enhances
      LDL uptake. These findings provide novel evidence for a central role of sialidase
      in the cross talk between the uptake and production of lipoproteins.

PMID- 22984146
TI  - No association between body size at birth and leucocyte telomere length in adult
      life--evidence from three cohort studies.
AB  - BACKGROUND: Shorter leucocyte telomere length (LTL) is a promising marker of
      biological ageing. It is predicted by cumulative adverse conditions throughout
      life course, but few studies have data from the prenatal period when most
      developmental processes and cell replication take place. We studied whether body
      size at birth and underlying factors including severely preterm birth predict LTL
      in adult life. METHODS: We used data from following three cohorts: (i) 1894
      subjects (age: 56-69 years) from the Helsinki Birth Cohort Study (HBCS),
      representing normal variation in fetal growth; (ii) the Helsinki Study of Very
      Low Birth Weight Adults encompassing 164 subjects born preterm at very low
      birthweight (<1500 g; representing extreme pre- and neonatal conditions) and 170
      term-born controls (18-27 years) and (iii) 248 twins (23-31 years) from the
      FinnTwin16 cohort, allowing comparisons between twin pairs. Relative telomere
      length was measured from leucocytes by real-time quantitative polymerase chain
      reaction. RESULTS: Shorter LTL was associated with higher age in HBCS and among
      men in the Helsinki Study of Very Low Birth Weight Adults and with lower
      childhood socio-economic status in HBCS and FinnTwin16. LTL was not associated
      with weight, length or gestational age at birth in any cohort. LTL was similar in
      very-low-birthweight and control subjects. CONCLUSIONS: LTL is unlikely to be a
      useful marker of a mechanism linking body size at birth with individual
      differences in ageing in the general population.

PMID- 22984148
TI  - Cohort profile: The Cork and Kerry Diabetes and Heart Disease Study.

PMID- 22984147
TI  - Differences in body composition between infants of South Asian and European
      ancestry: the London Mother and Baby Study.
AB  - BACKGROUND: South Asian children and adults have a more adipose body composition
      compared with those of European ancestry. This is thought to be related to their
      increased risk of metabolic disorders. However, little is known about how early
      in life such differences are manifest. OBJECTIVE: To determine whether there are
      differences in fat mass (FM) and fat-free mass (FFM) between UK-born South Asians
      and White Europeans in infancy. Design A cross-sectional study of 30 South Asian
      and 30 White European infants aged 6-12 weeks. Mothers were recruited from
      clinics in London, and infants' FM and FFM were determined using air-displacement
      plethysmography (PeaPod((r))). RESULTS: In early infancy South Asians had less
      FFM than White Europeans [0.34 kg less, 95% confidence interval (CI): 0.15,
      0.52], with a considerably weaker indication of them also having more FM (0.02 kg
      more, 95% CI: -0.14, 0.18). These differences persisted when the overall smaller
      body size of South Asian infants was taken into account. For a given total infant
      weight, the balance of body composition of South Asians was shifted by 0.16 kg
      (95% CI: 0.06, 0.25) from FFM to FM. The ethnic differences in the amount of FFM
      were almost completely accounted for by ethnic differences in the rate of growth
      in utero and length of gestation. CONCLUSIONS: The characteristic differences in
      body composition observed between adult South Asians and White Europeans are
      apparent in early infancy. Of particular note is that this is the first study to
      demonstrate that South Asians compared with White Europeans have reduced FFM in
      infancy. The early manifestation of this phenotype suggests that it is either
      genetic and/or determined through exposure to maternal physiology, rather than a
      consequence of behaviours or diet in childhood or at older ages.

PMID- 22984149
TI  - Special article: Nicholas M. Greene: visionary educator, clinician, editor, and
      humanitarian.

PMID- 22984150
TI  - Paravertebral blockade for day-case breast augmentation: a randomized clinical
      trial.
AB  - BACKGROUND: Bilateral breast augmentation is an increasingly popular day-case
      procedure. Local infiltration with sedation is routinely used for its ease of
      application compared with the more complex and potentially riskier paravertebral
      blockade (PVB). We hypothesized that ropivacaine injected by experienced
      anesthesia providers into the paravertebral space as a PVB was more effective
      than ropivacaine injected by the operating surgeon (plastic surgeon) directly
      into the zone of surgical dissection. METHODS: Forty female patients who were ASA
      physical status I or II and undergoing bilateral subpectoral cosmetic breast
      augmentation were recruited for participation in a prospective, randomized,
      single-blind study. Patients were randomized to 1 of 2 groups: ropivacaine via
      PVB, or surgical infiltration of ropivacaine. In both groups, the surgeon was
      asked to infiltrate the appropriate area with either saline (PVB group) or
      ropivacaine (local infiltration group). Both groups were sedated with propofol,
      titrated to effect. The plastic surgeon was blinded to the solution injected.
      Data collected included demographic characteristics, intraoperative cooperation
      scores, recovery room postoperative nausea and vomiting, analgesia use, and
      visual analog scale pain scores. All patients were asked to complete a
      preoperative anxiety and quality of recovery questionnaire and to record their
      pain scores and analgesia requirements on discharge. The outcome measures were
      (i) intraoperative patient cooperation as assessed by the plastic surgeon, (ii)
      propofol requirement, (iii) postoperative pain, and (iv) quality of recovery.
      RESULTS: Forty patients completed the study. PVB improved intraoperative
      cooperation (significance of difference P < 0.001, WMWodds = 6.69 with 95% 1
      sided confidence interval CI >=2.85), reduced propofol requirement (significance
      of difference P = 0.005, WMWodds = 0.35, CI <0.69), and decreased average
      postoperative pain in the home environment (significance of difference P = 0.007,
      WMWodds = 0.38, CI <0.73). There were no PVB complications. Only patients from
      the surgical infiltration group required rescue analgesics (30%, significance of
      difference = 0.01). CONCLUSIONS: In a limited number of patients, we found that
      PVB is superior to direct surgical infiltration of ropivacaine for bilateral
      breast augmentation in same-day surgery. These advantages need to be balanced
      against the potential risks of PVB, especially in an office setting.

PMID- 22984151
TI  - Similar liability for trauma and nontrauma surgical anesthesia: a closed claims
      analysis.
AB  - BACKGROUND: Trauma care has many challenges, including the perception by
      nonanesthesia physicians of increased medical malpractice liability. We used the
      American Society of Anesthesiologists' Closed Claims Project database and the
      National Inpatient Sample (NIS) to compare the rate of claims for trauma
      anesthesia care to national trauma surgery data. We also used the American
      Society of Anesthesiologists' Closed Claims Project database to evaluate injury
      and liability profiles of trauma anesthesia malpractice claims compared to
      nontrauma surgical anesthesia claims. METHODS: Surgical anesthesia claims for
      injuries that occurred between 1980 and 2005 in the American Society of
      Anesthesiologists' Closed Claims Project database of 8954 claims were included in
      this analysis. Trauma was defined using cause of injury criteria in state trauma
      registries, including out-of-hospital falls. To estimate national trauma
      anesthesia rates, we used injury codes in NIS reports to define trauma discharges
      and NIS discharges with surgical procedure codes for the denominator. The year
      adjusted odds ratio and P value comparing the national trauma anesthesia injury
      rates and American Society of Anesthesiologists' Closed Claims Project inpatient
      claim rates in the 1990 to 2001 time period were calculated by a multivariate
      logistic regression of the injury/trauma outcome on year and the NIS/Closed
      Claims Project indicator. Payments in claim resolution between trauma claims and
      nontraumatic surgical anesthesia claims were compared by chi(2) analysis, Fisher
      exact test for proportions, and Kolmogorov-Smirnov test for payment amounts.
      RESULTS: Trauma claims represented 6% of the total 6215 surgical anesthesia
      claims in the study period. The inpatient trauma claims rates were consistently
      lower than the NIS injury rates for 1990 to 2001. The year-adjusted odds ratio
      comparing the trauma claims rates to the NIS injury rates was 0.62 (95%
      confidence interval [CI], 0.53 to 0.72; P < 0.001, likelihood ratio test). Trauma
      claims and nontrauma surgical anesthesia claims did not differ in appropriateness
      of care, whether or not a payment was made to the plaintiff, or size of payments.
      CONCLUSION: Despite reported perceptions that trauma care involves a high risk of
      medical liability, there was no apparent increased risk of liability among
      inpatients presenting for trauma anesthesia care. The proportion in malpractice
      claims in trauma anesthesia care was not increased compared to nontraumatic
      surgical anesthesia care. With respect to medicolegal liability, these results
      support participation of anesthesia providers in multidisciplinary trauma care
      and organized systems.

PMID- 22984152
TI  - Multitasking during patient handover in the recovery room.
AB  - BACKGROUND: Loss of information occurs frequently during handover and affects the
      continuity of care. Improving handovers is therefore a key patient safety goal.
      After surgery, the patient is transferred to the postanesthesia care unit (PACU),
      and handover to the nurse includes both handover of monitoring equipment
      (connecting electrocardiogram, calibrating arterial lines, infusion pumps, etc.)
      and patient/procedure-specific information. Multitasking is likely to increase
      the risk of information loss during handover. It is unknown to what extent the
      transfer of equipment and information occurs simultaneously or sequentially in
      daily practice. METHODS: A nationwide questionnaire on the subject of patient
      handover was returned by 494 health care practitioners concerned with handovers
      from operating room (OR) to PACU. In addition, 101 handovers from the OR to the
      PACU were videotaped in 2 academic hospitals (n = 20), 3 teaching hospitals (n =
      43) and 1 community hospital (n = 38). The occurrence of simultaneous or
      sequential transfer of equipment and information was recorded by two independent
      observers. RESULTS: Simultaneous handover of equipment and information was the
      preference for a minority of respondents to the national survey (11%, 95%
      confidence interval, 8% to 14%). Self-reported simultaneous handover was 43% (39%
      to 47%). In the videotaped handovers, simultaneous handover was used for 65% (56%
      to 74%), which was even higher in the academic centers. The simultaneous
      handovers were no more than 0.2 minute faster than sequential handovers (P =
      0.38). CONCLUSIONS: In most videotaped handovers from OR to the PACU, there was
      simultaneous transfer of equipment and information. Although most health care
      providers are unaware of it, this form of multitasking during patient handover in
      the PACU is common. Future studies should evaluate whether this multitasking also
      leads to loss of critical patient information and reduced patient safety.

PMID- 22984153
TI  - What's new in obstetric anesthesia in 2011? Reducing maternal adverse outcomes
      and improving obstetric anesthesia quality of care.
AB  - This article accompanied the "What's New in Obstetric Anesthesia?" lecture
      presented at the Society for Obstetric Anesthesia and Perinatology Annual Meeting
      in May 2012. The invited lecturer reviewed the obstetric, obstetric
      anesthesiology, perinatology, and key medical literature published in 2011. This
      review identifies key topics and themes from the 2011 literature relevant to the
      science and clinical practice of obstetric anesthesiology and the
      interdisciplinary care of obstetric patients. Specific topics include health care
      policy issues that affect pregnant women, updated information on maternal
      mortality and morbidity, and clinical and outcomes-based research related to
      anesthetic practices for women undergoing cesarean delivery.

PMID- 22984154
TI  - Paracetamol does not compromise early wound repair in the intestine or abdominal
      wall in the rat.
AB  - BACKGROUND: Paracetamol is a cornerstone for perioperative pain relief. Its
      mechanism of action may include a local anti-inflammatory effect with inhibition
      of cyclooxygenase isoenzymes. The scarce literature available on its effects on
      wound healing consists of preclinical studies into the effect of paracetamol on
      healing of the musculoskeletal system. Although the drug is used abundantly for
      pain relief after surgery of the gastrointestinal tract, there are no published
      data on the influence of paracetamol on anastomotic and abdominal healing. This
      also holds for the crucial, early inflammatory phase of repair. The recovery of
      wound strength could therefore conceivably be affected by paracetamol. METHODS:
      In 78 male Wistar rats, we constructed an anastomosis in colon and ileum. The
      rats received either low- or high-dose (50 or 200 mg/kg/d, divided over 2 doses)
      paracetamol or vehicle (controls) until they were killed on day 3 or 7 after
      surgery (n = 13 each). In anastomoses, the main outcome variables were 2
      independent measures for wound strength, bursting pressure, and breaking
      strength, the latter being the primary outcome variable. In addition, collagen
      levels were measured and histology was performed. In fascia, breaking strength
      was analyzed. RESULTS: No significant differences were found between control and
      paracetamol-treated groups at any time point for any of the variables. Wound
      strength increased significantly from day 3 to day 7 in all groups. In the colon
      anastomosis, the breaking strength increased from 130 +/- 9 g (mean +/- SEM) at
      day 3 to 232 +/- 17 g at day 7 in the control group, from 144 +/- 10 to 224 +/- 9
      g in the low-dose group, and from 130 +/- 12 to 263 +/- 28 g in the high-dose
      group. The lower limit for the 95% confidence interval was -11 for the difference
      between control and low-dose groups at day 3 and -25 for the difference between
      control and high-dose groups. No differences in collagen levels were found
      between the high-dose and control groups. Histology did not indicate the presence
      of gross differences between groups. CONCLUSIONS: Perioperative use of
      paracetamol in a rat model of intestinal surgery does not significantly impede
      wound repair in the early postoperative period.

PMID- 22984155
TI  - Inhaled fentanyl aerosol in healthy volunteers: pharmacokinetics and
      pharmacodynamics.
AB  - BACKGROUND: Rapid delivery of potent opioid to the systemic circulation is an
      important feature for the effective treatment of acute and acute-on-chronic
      breakthrough pain. The delivery of different opioids by the pulmonary route has
      been inconsistent, usually resulting in low bioavailability of the drug.
      Staccato(r) Fentanyl for Inhalation is a handheld inhaler producing a single
      metered dose of aerosolized fentanyl during a single inspiration. The aerosol is
      of high purity (>=98%) at a particle size (1 to 3.5 microns) shown to be best for
      pulmonary absorption. METHODS: We conducted the study in healthy volunteers in 2
      stages. In the crossover stage, 10 subjects received IV fentanyl 25 ug and
      inhaled fentanyl 25 ug on separate occasions. The dose escalation stage was a
      multidose, randomized, double-blind, placebo-controlled, single-period dose
      escalation study of inhaled fentanyl (50 to 300 ug). Serial blood sampling was
      performed over an 8-hour period after drug administration to determine the
      pharmacokinetic profile, and serial pupillometry was performed as a measure of
      pharmacodynamic effect. RESULTS: In the crossover stage the pharmacokinetic
      profiles of the inhaled and IV fentanyl showed similar peak arterial
      concentrations and areas under the curve. The time to maximum concentration was
      slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds,
      respectively. In the dose escalation stage the administration of repeated doses
      resulted in predictable, dose-dependent serum concentrations. CONCLUSIONS: This
      study has demonstrated that the pharmacokinetic profile of single doses of
      inhaled fentanyl is comparable to IV administration.

PMID- 22984157
TI  - Toward a metabolic scaling theory of crop systems.

PMID- 22984156
TI  - Physical manipulation of the Escherichia coli chromosome reveals its soft nature.
AB  - Replicating bacterial chromosomes continuously demix from each other and
      segregate within a compact volume inside the cell called the nucleoid. Although
      many proteins involved in this process have been identified, the nature of the
      global forces that shape and segregate the chromosomes has remained unclear
      because of limited knowledge of the micromechanical properties of the chromosome.
      In this work, we demonstrate experimentally the fundamentally soft nature of the
      bacterial chromosome and the entropic forces that can compact it in a crowded
      intracellular environment. We developed a unique "micropiston" and measured the
      force-compression behavior of single Escherichia coli chromosomes in confinement.
      Our data show that forces on the order of 100 pN and free energies on the order
      of 10(5) k(B)T are sufficient to compress the chromosome to its in vivo size. For
      comparison, the pressure required to hold the chromosome at this size is a
      thousand-fold smaller than the surrounding turgor pressure inside the cell.
      Furthermore, by manipulation of molecular crowding conditions (entropic forces),
      we were able to observe in real time fast (approximately 10 s), abrupt,
      reversible, and repeatable compaction-decompaction cycles of individual
      chromosomes in confinement. In contrast, we observed much slower dissociation
      kinetics of a histone-like protein HU from the whole chromosome during its in
      vivo to in vitro transition. These results for the first time provide
      quantitative, experimental support for a physical model in which the bacterial
      chromosome behaves as a loaded entropic spring in vivo.

PMID- 22984158
TI  - Looking beyond overnutrition for causes of epidemic metabolic disease.

PMID- 22984159
TI  - Polymer scaling laws of unfolded and intrinsically disordered proteins quantified
      with single-molecule spectroscopy.
AB  - The dimensions of unfolded and intrinsically disordered proteins are highly
      dependent on their amino acid composition and solution conditions, especially
      salt and denaturant concentration. However, the quantitative implications of this
      behavior have remained unclear, largely because the effective theta-state, the
      central reference point for the underlying polymer collapse transition, has
      eluded experimental determination. Here, we used single-molecule fluorescence
      spectroscopy and two-focus correlation spectroscopy to determine the theta points
      for six different proteins. While the scaling exponents of all proteins converge
      to 0.62 +/- 0.03 at high denaturant concentrations, as expected for a polymer in
      good solvent, the scaling regime in water strongly depends on sequence
      composition. The resulting average scaling exponent of 0.46 +/- 0.05 for the four
      foldable protein sequences in our study suggests that the aqueous cellular milieu
      is close to effective theta conditions for unfolded proteins. In contrast, two
      intrinsically disordered proteins do not reach the Theta-point under any of our
      solvent conditions, which may reflect the optimization of their expanded state
      for the interactions with cellular partners. Sequence analyses based on our
      results imply that foldable sequences with more compact unfolded states are a
      more recent result of protein evolution.

PMID- 22984161
TI  - Longer time scale for human evolution.

PMID- 22984162
TI  - Inhibitory cross-talk upon introduction of a new metabolic pathway into an
      existing metabolic network.
AB  - Evolution or engineering of novel metabolic pathways can endow microbes with new
      abilities to degrade anthropogenic pollutants or synthesize valuable chemicals.
      Most studies of the evolution of new pathways have focused on the origins and
      quality of function of the enzymes involved. However, there is an additional
      layer of complexity that has received less attention. Introduction of a novel
      pathway into an existing metabolic network can result in inhibitory cross-talk
      due to adventitious interactions between metabolites and macromolecules that have
      not previously encountered one another. Here, we report a thorough examination of
      inhibitory cross-talk between a novel metabolic pathway for synthesis of
      pyridoxal 5'-phosphate and the existing metabolic network of Escherichia coli. We
      demonstrate multiple problematic interactions, including (i) interference by
      metabolites in the novel pathway with metabolic processes in the existing
      network, (ii) interference by metabolites in the existing network with the
      function of the novel pathway, and (iii) diversion of metabolites from the novel
      pathway by promiscuous activities of enzymes in the existing metabolic network.
      Identification of the mechanisms of inhibitory cross-talk can reveal the types of
      adaptations that must occur to enhance the performance of a novel metabolic
      pathway as well as the fitness of the microbial host. These findings have
      important implications for evolutionary studies of the emergence of novel
      pathways in nature as well as genetic engineering of microbes for "green"
      manufacturing processes.

PMID- 22984164
TI  - Waxy genes from spelt wheat: new alleles for modern wheat breeding and new
      phylogenetic inferences about the origin of this species.
AB  - BACKGROUND AND AIMS: Waxy proteins are responsible for amylose synthesis in wheat
      seeds, being encoded by three waxy genes (Wx-A1, Wx-B1 and Wx-D1) in hexaploid
      wheat. In addition to their role in starch quality, waxy loci have been used to
      study the phylogeny of wheat. The origin of European spelt (Triticum aestivum
      ssp. spelta) is not clear. This study compared waxy gene sequences of a Spanish
      spelt collection with their homologous genes in emmer (T. turgidum ssp.
      dicoccum), durum (T. turgidum ssp. durum) and common wheat (T. aestivum ssp.
      aestivum), together with other Asian and European spelt that could be used to
      determine the origin of European spelt. METHODS: waxy genes were amplified and
      sequenced. Geneious Pro software, DNAsp and MEGA5 were used for sequence,
      nucleotide diversity and phylogenetic analysis, respectively. KEY RESULTS: Three,
      four and three new alleles were described for the Wx-A1, Wx-B1 and Wx-D1 loci,
      respectively. Spelt accessions were classified into two groups based on the
      variation in Wx-B1, which suggests that there were two different origins for the
      emmer wheat that has been found to be part of the spelt genetic make-up. One of
      these groups was only detected in Iberian material. No differences were found
      between the rest of the European spelt and the Asiatic spelt, which suggested
      that the Iberian material had a different origin from the other spelt sources.
      CONCLUSIONS: The results suggested that the waxy gene variability present in
      wheat is undervalued. The evaluation of this variability has permitted the
      detection of ten new waxy alleles that could affect starch quality and thus could
      be used in modern wheat breeding. In addition, two different classes of Wx-B1
      were detected that could be used for evaluating the phylogenetic relationships
      and the origins of different types of wheat.

PMID- 22984166
TI  - Surplus suffering, mothers don't know best: denial of mothers' reality when
      parenting a child with mental health issues.
AB  - This paper reports on a qualitative interview study of 16 mothers whose children
      had received a diagnosis with one, or more, mental health issue. It is based on
      retrospective accounts from mothers describing the early days of noticing that
      something seemed a bit problematic with their child. When they tried to discuss
      their concerns and asked for advice from family and friends their concerns were
      usually dismissed. When they took the child to the doctor, the doctor initially
      denied the mother's own assessment of the child. Other professionals weighed in
      and often blamed the mother and denied her reality too. These findings are
      discussed in terms of the theories of surplus suffering, good and intensive
      mothering, mother blame and stigma. Implications for practice are considered.

PMID- 22984165
TI  - Apomixis and reticulate evolution in the Asplenium monanthes fern complex.
AB  - BACKGROUND AND AIMS: Asexual reproduction is a prominent evolutionary process
      within land plant lineages and especially in ferns. Up to 10 % of the approx. 10
      000 fern species are assumed to be obligate asexuals. In the Asplenium monanthes
      species complex, previous studies identified two triploid, apomictic species. The
      purpose of this study was to elucidate the phylogenetic relationships in the A.
      monanthes complex and to investigate the occurrence and evolution of apomixis
      within this group. METHODS: DNA sequences of three plastid markers and one
      nuclear single copy gene were used for phylogenetic analyses. Reproductive modes
      were assessed by examining gametophytic and sporophyte development, while
      polyploidy was inferred from spore measurements. KEY RESULTS: Asplenium monanthes
      and A. resiliens are confirmed to be apomictic. Asplenium palmeri, A. hallbergii
      and specimens that are morphologically similar to A. heterochroum are also found
      to be apomictic. Apomixis is confined to two main clades of taxa related to A.
      monanthes and A. resiliens, respectively, and is associated with reticulate
      evolution. Two apomictic A. monanthes lineages, and two putative diploid sexual
      progenitor species are identified in the A. monanthes clade. CONCLUSIONS:
      Multiple origins of apomixis are inferred, in both alloploid and autoploid forms,
      within the A. resiliens and A. monanthes clades.

PMID- 22984167
TI  - Informing parents about positive newborn screen results: parents'
      recommendations.
AB  - This descriptive study examined parents' reactions to newborn screening (NBS)
      results and their recommendations for improving communication. Dimensional and
      content analyses were conducted on interviews with 203 parents of 106 infants
      having positive NBS results. Diagnostic results confirmed infants as having
      congenital hypothyroidism (n = 37), cystic fibrosis (n = 26), or being cystic
      fibrosis (CF)-carriers (n = 43). Parents' reactions ranged from 'very scary' to
      'not too concerned'. Most reported feeling shock, panic, and worry; some reported
      guilt. Parents in the CF and CF-carrier groups preferred face-to-face disclosure
      as the communication channel; whereas congenital hypothyroidism group parents
      supported telephone contacts. Parents recommended providers be well informed,
      honest, and calm; personalize disclosure, avoid jargon, listen carefully,
      encourage questions, recognize parental distress, offer realistic reassurance,
      pace amount and rate of information, assess parents' understanding, and refer to
      specialists. We conclude that provider-patient communication approach and channel
      can exacerbate or alleviate parents' negative reactions to positive NBS results.

PMID- 22984168
TI  - A narrative literature review of the development of obesity in infancy and
      childhood.
AB  - This narrative review explains the development of excess weight gain in babies
      and children. It takes a life course approach which includes genetics, pre
      conception, pregnancy, infancy and childhood. The paper focuses on feeding
      behaviours, physical activity, parental influences and the wider social and
      environmental context. Risk factors which can cumulatively lead to excess
      childhood weight gain include: under- or overweight during pregnancy; the
      presence of diabetes during pregnancy; low or high birth weight; having obese
      parents; early weaning; prolonged formula feeding; rapid weight gain in the first
      year; disinhibited eating patterns and the consistent availability of energy
      dense food at home; feeding practices which are not responsive to the child's
      cues; insufficient sleep among preschool children; sedentary parents; low
      parental education; living in poor socio-economic circumstances; absence, or
      perceived absence, of safe play areas; parents who lack time or confidence to
      authoritatively parent; environments where there is poor access to affordable
      lower energy dense foods; and parents who do not accept that excess weight is a
      health problem. Recommendations for health professionals are made.

PMID- 22984169
TI  - Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid
      arthritis.
AB  - OBJECTIVE: To produce consensus-based scoring systems for ultrasound (US)
      tenosynovitis and to assess the intraobserver and interobserver reliability of
      these scoring systems in rheumatoid arthritis (RA). METHODS: We undertook a
      Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis
      in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16
      countries. Then, we assessed the intraobserver and interobserver reliability of
      US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique.
      Ten patients with RA with symptoms in the hands or feet were recruited. Ten
      rheumatologists expert in MSUS blindly, independently and consecutively scored
      for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two
      finger flexor tendons and two ankle tendons of each patient in two rounds in a
      blinded fashion. Intraobserver reliability was assessed by Cohen's kappa.
      Interobserver reliability was assessed by Light's kappa. Weighted kappa
      coefficients with absolute weighting were computed for B-mode and PD signal.
      RESULTS: Four-grade semiquantitative scoring systems were agreed upon for scoring
      tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal
      within the synovial sheath. The intraobserver reliability for tenosynovitis
      scoring on B-mode and PD mode was good (kappa value 0.72 for B-mode; kappa value
      0.78 for PD mode). Interobserver reliability assessment showed good kappa values
      for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate
      kappa values for B-mode tenosynovitis scoring (first round, 0.47; second round,
      0.45). CONCLUSIONS: US appears to be a reproducible tool for evaluating and
      monitoring tenosynovitis in RA.

PMID- 22984170
TI  - Serum urate association with hypertension in young adults: analysis from the
      Coronary Artery Risk Development in Young Adults cohort.
AB  - OBJECTIVE: To determine if serum urate concentration is associated with
      development of hypertension in young adults. METHODS: Retrospective cohort
      analysis from 4752 participants with available serum urate and without
      hypertension at baseline from the Coronary Artery Risk Development in Young
      Adults (CARDIA) study; a mixed race (African-American and White) cohort
      established in 1985 with 20 years of follow-up data for this analysis.
      Associations between baseline serum urate concentration and incident hypertension
      (defined as a blood pressure greater or equal to 140/90 or being on
      antihypertensive drugs) were investigated in sex-stratified bivariate and
      multivariable Cox-proportional analyses. RESULTS: Mean age (SD) at baseline was
      24.8 (3.6) years for men and 24.9 (3.7) years for women. Compared with the
      referent category, we found a greater hazard of developing hypertension starting
      at 345 umol/l (5.8 mg/dl) of serum urate for men and 214 umol/l (3.6 mg/dl) for
      women. There was a 25% increase in the hazard of developing hypertension in men
      (HR1.25 (95% CI 1.15 to 1.36)) per each mg/dl increase in serum urate but no
      significant increase in women (HR 1.06 (95%CI 0.97 to 1.16)). CONCLUSIONS: We
      found a significant independent association between higher serum urate
      concentrations and the subsequent hazard of incident hypertension, even at
      concentrations below the conventional hyperuricaemia threshold of 404 umol/l (6.8
      mg/dl).

PMID- 22984171
TI  - Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in
      ankylosing spondylitis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of an oral phosphodiesterase 4
      inhibitor, apremilast, in treatment of ankylosing spondylitis (AS) by monitoring
      symptoms and signs in a pilot study including exploratory investigation of
      effects of PDE4 inhibition on blood biomarkers of bone biology. METHODS: In this
      double-blind, placebo-controlled, single-centre, Phase II study, patients with
      symptomatic AS with active disease on MRI were randomised to apremilast 30 mg BID
      or placebo over 12 weeks. Bath Indices were monitored serially. Patients were
      followed for 4 weeks after stopping medication. Bone biomarkers were assessed at
      baseline and day 85. RESULTS: 38 subjects were randomised and 36 subjects
      completed the study. Although the primary end-point (change in BASDAI at week 12)
      was not met, apremilast was associated with numerically greater improvement from
      baseline for all clinical assessments compared with placebo with mean change in
      BASDAI (-1.59+/-1.48 vs -0.77+/-1.47), BASFI (-1.74+/-1.91 vs -0.28+/-1.61) and
      BASMI (-0.51+/-1.02 vs -0.21+/-0.67); however, differences did not achieve
      statistical significance. The clinical indices returned to baseline values by 4
      weeks after cessation of apremilast. Six apremilast patients (35.3%) vs 3 placebo
      (15.8%) achieved ASAS20 responses (p=0.25). There were statistically significant
      decreases in serum RANKL and RANKL:osteoprotegrin ratio and plasma sclerostin but
      no significant changes in serum DKK-1, bone alkaline phosphatase, TRAP5b, MMP3,
      osteoprotegrin, or osteocalcin. CONCLUSIONS: Although a small pilot study, these
      results suggest that apremilast may be effective and well tolerated in AS and
      modulates biomarkers of bone biology. These data support further research of
      apremilast in axial inflammation.

PMID- 22984172
TI  - No evidence of an association between mitochondrial DNA variants and
      osteoarthritis in 7393 cases and 5122 controls.
AB  - OBJECTIVES: Osteoarthritis (OA) has a complex aetiology with a strong genetic
      component. Genome-wide association studies implicate several nuclear genes in the
      aetiology, but a major component of the heritability has yet to be defined at the
      molecular level. Initial studies implicate maternally inherited variants of
      mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and
      specific joint involvement, but these findings have not been replicated. METHODS:
      The authors studied 138 maternally inherited mtDNA variants genotyped in a two
      cohort genetic association study across a total of 7393 OA cases from the arcOGEN
      consortium and 5122 controls genotyped in the Wellcome Trust Case Control
      consortium 2 study. RESULTS: Following data quality control we examined 48 mtDNA
      variants that were common in cohort 1 and cohort 2, and found no association with
      OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups
      were associated in this study. CONCLUSIONS: We were not able to replicate
      previously published findings in the largest mtDNA association study to date. The
      evidence linking OA to mtDNA is not compelling at present.

PMID- 22984173
TI  - Golimumab monotherapy in Japanese patients with active rheumatoid arthritis
      despite prior treatment with disease-modifying antirheumatic drugs: results of
      the phase 2/3, multicentre, randomised, double-blind, placebo-controlled GO-MONO
      study through 24 weeks.
AB  - OBJECTIVE: To evaluate the efficacy and safety of golimumab 50 and 100 mg
      monotherapy in Japanese patients with active rheumatoid arthritis (RA) despite
      treatment with disease-modifying antirheumatic drugs (DMARDs). METHODS: A total
      of 316 patients were randomised to receive subcutaneous injections every 4 weeks
      of placebo (group 1), golimumab 50 mg (group 2) or golimumab 100 mg (group 3);
      group 1 crossed over to golimumab 50 mg at week 16. The primary end point was the
      proportion of patients achieving >=20% improvement in the American College of
      Rheumatology criteria (ACR20) at week 14. ACR50 and ACR70 response rates were
      also measured. Adverse events (AEs) were monitored throughout the study. RESULTS:
      Demographics were similar across groups; the mean age was 52 years and 81.8% of
      patients (252/308) were female. Week 14 ACR20 response rates were significantly
      greater in groups 2 (51/101 (50.5%)) and 3 (60/102 (58.8%)) than in group 1
      (20/105 (19.0%); p<0.0001 for both), as were ACR50 and ACR70 response rates.
      After placebo crossover at week 16, week 24 ACR response rates were similar in
      groups 1 and 2. Through week 16, 63.8% of patients in group 1, 62.4% in group 2
      and 60.8% in group 3 had AEs and 1.9%, 1.0% and 2.0% had serious AEs. After week
      16, one malignancy was reported (breast cancer, group 3). Infections were the
      most common AEs. No deaths or cases of tuberculosis were reported through week
      24. CONCLUSIONS: Golimumab monotherapy (50 and 100 mg) was effective in reducing
      the signs and symptoms of RA in Japanese patients with active disease despite
      DMARD treatment.

PMID- 22984174
TI  - Application of the 2010 ACR/EULAR classification criteria in patients with very
      early inflammatory arthritis: analysis of sensitivity, specificity and predictive
      values in the SAVE study cohort.
AB  - OBJECTIVE: Performance of the 2010 American College of Rheumatology
      (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA)
      criteria was analysed in an internationally recruited early arthritis cohort
      (<=16 weeks symptom duration) enrolled in the 'Stop-Arthritis-Very-Early' trial.
      This sample includes patients with a variety of diseases diagnosed during follow
      up. METHODS: Two endpoints were defined: Investigators' diagnosis and disease
      modifying antirheumatic drug (DMARD) treatment start during the 12-month follow
      up. The 2010 criteria were applied to score Patients' baseline data. Sensitivity,
      specificity, predictive values and areas under the receiver operating curves of
      this scoring with respect to both endpoints were calculated and compared to the
      1987 criteria. The optimum level of agreement between the endpoints and the 2010
      classification score ways estimated by Cohen's kappa coefficients. RESULTS: 303
      patients had 12-months follow-up. Positive predictive values of the 2010 criteria
      were 0.68 and 0.71 for RA-diagnosis and DMARD-start, respectively. Sensitivity
      for RA-diagnosis was 0.85, for DMARD-start 0.8, whereas the 1987 criteria's
      sensitivities were 0.65 and 0.55. The areas under the receiver operating curves
      of the 2010 criteria for RA-diagnosis and DMARD-start were 0.83 and 0.78.
      Analysis of inter-rater-agreement using Cohen's kappa demonstrated the highest
      kappa values (0.5 for RA-diagnosis and 0.43 for DMARD-start) for the score of 6.
      CONCLUSIONS: In this international very early arthritis cohort predictive and
      discriminative abilities of the 2010 ACR/EULAR classification criteria were
      satisfactory and substantially superior to the 'old' 1987 classification
      criteria. This easier classification of RA in early stages will allow targeting
      truly early disease stages with appropriate therapy.

PMID- 22984176
TI  - Chromatin conformation governs T-cell receptor Jbeta gene segment usage.
AB  - T cells play fundamental roles in adaptive immunity, relying on a diverse
      repertoire of T-cell receptor (TCR) alpha and beta chains. Diversity of the TCR
      beta chain is generated in part by a random yet intrinsically biased
      combinatorial rearrangement of variable (Vbeta), diversity (Dbeta), and joining
      (Jbeta) gene segments. The mechanisms that determine biases in gene segment use
      remain unclear. Here we show, using a high-throughput TCR sequencing approach,
      that a physical model of chromatin conformation at the DJbeta genomic locus
      explains more than 80% of the biases in Jbeta use that we measured in murine T
      cells. This model also predicts correctly how differences in intersegment genomic
      distances between humans and mice translate into differences in Jbeta bias
      between TCR repertoires of these two species. As a consequence of these
      structural and other biases, TCR sequences are produced with different a priori
      frequencies, thus affecting their probability of becoming public TCRs that are
      shared among individuals. Surprisingly, we find that many more TCR sequences are
      shared among all five mice we studied than among only subgroups of three or four
      mice. We derive a necessary mathematical condition explaining this finding, which
      indicates that the TCR repertoire contains a core set of receptor sequences that
      are highly abundant among individuals, if their a priori probability of being
      produced by the recombination process is higher than a defined threshold. Our
      results provide evidence for an expanded role of chromatin conformation in VDJ
      rearrangement, from control of gene accessibility to precise determination of
      gene segment use.

PMID- 22984175
TI  - Phylogenies reveal predictive power of traditional medicine in bioprospecting.
AB  - There is controversy about whether traditional medicine can guide drug discovery,
      and investment in bioprospecting informed by ethnobotanical data has fluctuated.
      One view is that traditionally used medicinal plants are not necessarily
      efficacious and there are no robust methods for distinguishing those which are
      most likely to be bioactive when selecting species for further testing. Here, we
      reconstruct a genus-level molecular phylogenetic tree representing the 20,000
      species found in the floras of three disparate biodiversity hotspots: Nepal, New
      Zealand, and the Cape of South Africa. Borrowing phylogenetic methods from
      community ecology, we reveal significant clustering of the 1,500 traditionally
      used species, and provide a direct measure of the relatedness of the three
      medicinal floras. We demonstrate shared phylogenetic patterns across the floras:
      related plants from these regions are used to treat medical conditions in the
      same therapeutic areas. This finding strongly indicates independent discovery of
      plant efficacy, an interpretation corroborated by the presence of a significantly
      greater proportion of known bioactive species in these plant groups than in
      random samples. We conclude that phylogenetic cross-cultural comparisons can
      focus screening efforts on a subset of traditionally used plants that are richer
      in bioactive compounds, and could revitalize the use of traditional knowledge in
      bioprospecting.

PMID- 22984177
TI  - Brain imaging reveals neuronal circuitry underlying the crow's perception of
      human faces.
AB  - Crows pay close attention to people and can remember specific faces for several
      years after a single encounter. In mammals, including humans, faces are evaluated
      by an integrated neural system involving the sensory cortex, limbic system, and
      striatum. Here we test the hypothesis that birds use a similar system by
      providing an imaging analysis of an awake, wild animal's brain as it performs an
      adaptive, complex cognitive task. We show that in vivo imaging of crow brain
      activity during exposure to familiar human faces previously associated with
      either capture (threatening) or caretaking (caring) activated several brain
      regions that allow birds to discriminate, associate, and remember visual stimuli,
      including the rostral hyperpallium, nidopallium, mesopallium, and lateral
      striatum. Perception of threatening faces activated circuitry including
      amygdalar, thalamic, and brainstem regions, known in humans and other vertebrates
      to be related to emotion, motivation, and conditioned fear learning. In contrast,
      perception of caring faces activated motivation and striatal regions. In our
      experiments and in nature, when perceiving a threatening face, crows froze and
      fixed their gaze (decreased blink rate), which was associated with activation of
      brain regions known in birds to regulate perception, attention, fear, and escape
      behavior. These findings indicate that, similar to humans, crows use
      sophisticated visual sensory systems to recognize faces and modulate behavioral
      responses by integrating visual information with expectation and emotion. Our
      approach has wide applicability and potential to improve our understanding of the
      neural basis for animal behavior.

PMID- 22984178
TI  - Altered Ig levels and antibody responses in mice deficient for the Fc receptor
      for IgM (FcMUR).
AB  - Cell surface Fc receptor for IgM antibody (FcMUR) is the most recently identified
      member among FcRs. We determined the cellular distribution of mouse FcMUR and the
      functional consequences of Fcmr disruption. Surface FcMUR expression was
      restricted to B-lineage cells, from immature B to plasma cells, except for a
      transient down-modulation during germinal center reactions. Fcmr ablation had no
      significant effect on overall B- and T-cell development, but led to a reduction
      of marginal zone B cells and an increase in splenic B1 B cells. Preimmune serum
      IgM in mutant mice was significantly elevated as were natural autoantibodies.
      When immunized with live attenuated pneumococci, mutant mice mounted robust
      antibody responses against phosphorylcholine, but not protein, determinants
      compared with wild-type mice. By contrast, upon immunization with a hapten
      carrier conjugate, nitrophenyl-coupled chicken gamma-globulin (NP-CGG), the
      mutant mice had a diminished primary IgG1 response to both NP and CGG. These
      findings suggest that FcMUR has an important role in IgM homeostasis and
      regulation of humoral immune responses.

PMID- 22984179
TI  - Suomi satellite brings to light a unique frontier of nighttime environmental
      sensing capabilities.
AB  - Most environmental satellite radiometers use solar reflectance information when
      it is available during the day but must resort at night to emission signals from
      infrared bands, which offer poor sensitivity to low-level clouds and surface
      features. A few sensors can take advantage of moonlight, but the inconsistent
      availability of the lunar source limits measurement utility. Here we show that
      the Day/Night Band (DNB) low-light visible sensor on the recently launched Suomi
      National Polar-orbiting Partnership (NPP) satellite has the unique ability to
      image cloud and surface features by way of reflected airglow, starlight, and
      zodiacal light illumination. Examples collected during new moon reveal not only
      meteorological and surface features, but also the direct emission of airglow
      structures in the mesosphere, including expansive regions of diffuse glow and
      wave patterns forced by tropospheric convection. The ability to leverage diffuse
      illumination sources for nocturnal environmental sensing applications extends the
      advantages of visible-light information to moonless nights.

PMID- 22984180
TI  - Rice phytochrome-interacting factor-like protein OsPIL1 functions as a key
      regulator of internode elongation and induces a morphological response to drought
      stress.
AB  - The mechanisms for plant growth restriction during stress conditions remains
      unclear. Here, we demonstrate that a phytochrome-interacting factor-like protein,
      OsPIL1/OsPIL13, acts as a key regulator of reduced internode elongation in rice
      under drought conditions. The level of OsPIL1 mRNA in rice seedlings grown under
      nonstressed conditions with light/dark cycles oscillated in a circadian manner
      with peaks in the middle of the light period. Under drought stress conditions,
      OsPIL1 expression was inhibited during the light period. We found that OsPIL1 was
      highly expressed in the node portions of the stem using promoter-glucuronidase
      analysis. Overexpression of OsPIL1 in transgenic rice plants promoted internode
      elongation. In contrast, transgenic rice plants with a chimeric repressor
      resulted in short internode sections. Alteration of internode cell size was
      observed in OsPIL1 transgenic plants, indicating that differences in cell size
      cause the change in internode length. Oligoarray analysis revealed OsPIL1
      downstream genes, which were enriched for cell wall-related genes responsible for
      cell elongation. These data suggest that OsPIL1 functions as a key regulatory
      factor of reduced plant height via cell wall-related genes in response to drought
      stress. This regulatory system may be important for morphological stress
      adaptation in rice under drought conditions.

PMID- 22984181
TI  - Activation of Escherichia coli antiterminator BglG requires its phosphorylation.
AB  - Transcriptional antiterminator proteins of the BglG family control the expression
      of enzyme II (EII) carbohydrate transporters of the bacterial phosphotransferase
      system (PTS). In the PTS, phosphoryl groups are transferred from
      phosphoenolpyruvate (PEP) via the phosphotransferases enzyme I (EI) and HPr to
      the EIIs, which phosphorylate their substrates during transport. Activity of the
      antiterminators is negatively controlled by reversible phosphorylation catalyzed
      by the cognate EIIs in response to substrate availability and positively
      controlled by the PTS. For the Escherichia coli BglG antiterminator, two
      different mechanisms for activation by the PTS were proposed. According to the
      first model, BglG is activated by HPr-catalyzed phosphorylation at a site
      distinct from the EII-dependent phosphorylation site. According to the second
      model, BglG is not activated by phosphorylation, but solely through interaction
      with EI and HPr, which are localized at the cell pole. Subsequently BglG is
      released from the cell pole to the cytoplasm as an active dimer. Here we
      addressed this discrepancy and found that activation of BglG requires
      phosphorylatable HPr or the HPr homolog FruB in vivo. Further, we uniquely
      demonstrate that purified BglG protein becomes phosphorylated by FruB as well as
      by HPr in vitro. Histidine residue 208 in BglG is essential for this
      phosphorylation. These data suggest that BglG is in fact activated by
      phosphorylation and that there is no principal difference between the PTS-exerted
      mechanisms controlling the activities of BglG family proteins in Gram-positive
      and Gram-negative bacteria.

PMID- 22984183
TI  - QnAs with Subra Suresh. Interview by Prashant Nair.

PMID- 22984182
TI  - Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant
      mice.
AB  - Male infertility is most commonly caused by spermatogenic defects or
      insufficiencies, the majority of which are as yet cureless. Recently, we
      succeeded in cultivating mouse testicular tissues for producing fertile sperm
      from spermatogonial stem cells. Here, we show that one of the most severe types
      of spermatogenic defect mutant can be treated by the culture method without any
      genetic manipulations. The Sl/Sl(d) mouse is used as a model of such male
      infertility. The testis of the Sl/Sl(d) mouse has only primitive spermatogonia as
      germ cells, lacking any sign of spermatogenesis owing to mutations of the c-kit
      ligand (KITL) gene that cause the loss of membrane-bound-type KITL from the
      surface of Sertoli cells. To compensate for the deficit, we cultured testis
      tissues of Sl/Sl(d) mice with a medium containing recombinant KITL and found that
      it induced the differentiation of spermatogonia up to the end of meiosis. We
      further discovered that colony stimulating factor-1 (CSF-1) enhances the effect
      of KITL and promotes spermatogenesis up to the production of sperm.
      Microinsemination of haploid cells resulted in delivery of healthy offspring.
      This study demonstrated that spermatogenic impairments can be treated in vitro
      with the supplementation of certain factors or substances that are insufficient
      in the original testes.

PMID- 22984184
TI  - Aortic intramural haematoma: pathogenesis, clinical features and imaging
      evaluation.
AB  - Intramural haematoma (IMH) is a localised haemorrhage within the aortic wall.
      Imaging plays a central role in diagnosing IMH, differentiating it from aortic
      dissection (AD) and assessing for complications. Imaging is also important for
      prognostication and to help guide clinical decision making as a number of imaging
      characteristics have been correlated with increased mortality rates including
      location, mural thickness and aortic diameter. Multidetector CT is the leading
      technique for diagnosis and classification of IMH owing to speed of image
      acquisition, multiplanar capabilities and excellent spatial resolution. MRI is
      rarely used to investigate the initial presentation of IMH but is frequently used
      for serial follow-up studies. The clinical outcome of IMH may be favourable, with
      spontaneous regression over time, or it may be complicated by pericardial
      tamponade, aortic regurgitation and development of AD. Early surgical management
      is the treatment of choice for patients with Stanford type A IMH whereas most
      patients with Stanford type B IMH have a good short-term outcome with aggressive
      control of hypertension. This article reviews the pathogenesis, clinical features
      and complications of IMH as well as the role of advanced imaging techniques in
      its evaluation.

PMID- 22984185
TI  - Sleep quality and nocturnal hypoxaemia and hypercapnia in children and young
      adults with cystic fibrosis.
AB  - OBJECTIVES: The aim of the study was to evaluate sleep quality and nocturnal gas
      exchange in patients with cystic fibrosis (CF) and to assess if sleep quality and
      daytime lung function could predict nocturnal hypoxaemia or hypercapnia. STUDY
      DESIGN: Daytime sleepiness and objective sleep quality were evaluated by the
      Pittsburgh Sleep Quality Index (PSQI) and actigraphy in 25 children and 55 young
      adults (mean age 24+/-10 years, forced expiratory volume in 1 s (FEV(1)) 41+/-11%
      predicted). Nocturnal gas exchange was assessed by pulse oximetry (SpO(2)) and
      transcutaneous carbon dioxide (PtcCO(2)) recordings. Eleven patients underwent
      simultaneous polysomnography (PSG). RESULTS: PSQI was 6.3+/-3.4 with 51% of the
      patients having a score >5 corresponding to significant sleep complaints. On
      actigraphy, sleep efficiency was impaired at 79+/-11% with a fragmentation index
      at 41+/-18. Mean nocturnal SpO(2) was 93+/-3% with 18% of the patients exhibiting
      >10% of night time spent with a value below 90%. Mean PtcCO(2) was 44+/-6 mm Hg
      with 47% of the patients exhibiting >10% of night time with a value >45 mm Hg.
      Daytime arterial blood gases correlated with nocturnal gas exchange. FEV(1) was
      the only lung function parameter that correlated with nocturnal SpO(2) (p<0.01).
      Compared with PSG, SpO(2) and PtcCO(2) accurately identified rapid eye movement
      sleep hypoventilation. CONCLUSIONS: Patients with CF exhibit poor sleep quality
      that does not predict nocturnal gas exchange. Nocturnal hypoxaemia and
      hypercapnia can be identified by simple tools.

PMID- 22984186
TI  - Smartphone technology in the paediatric setting.

PMID- 22984187
TI  - Prospects for eradication of meningococcal disease.
AB  - Meningococcal meningitis and septicaemia remain a serious global health threat.
      This review focuses on the epidemiology of meningococcal disease following the
      recent implementation of effective vaccines and the potential utility of a
      vaccine against serogroup B meningococcus.

PMID- 22984188
TI  - Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell
      carcinoma with dual-energy CT.
AB  - PURPOSE: To evaluate the clinical usefulness of dual-energy computed tomography
      (CT) with weighted-average (WA) images and iodine overlay (IO) images in the
      evaluation of laryngeal cartilage invasion in patients with laryngeal and
      hypopharyngeal squamous cell carcinoma (SCC). MATERIALS AND METHODS: The
      institutional review board approved this retrospective study, and written
      comprehensive consent was obtained from all patients. Seventy-two consecutive
      patients underwent 128-section dual-source dual-energy CT to stage laryngeal
      (n=27) or hypopharyngeal (n=45) cancer. Three observers who were blinded to the
      patients' clinical histories and histopathologic findings evaluated cartilage
      invasion on WA images alone or in combination with IO images (nonossified
      cartilages were selectively evaluated on IO images) by using a five-point scale.
      Thirty of the 72 patients (42%) underwent surgery, and findings from
      histopathologic examination in those patients were used as the standard of
      reference for the evaluation of diagnostic performance with receiver operating
      characteristic (ROC) curve analysis and in terms of sensitivity and specificity.
      Interobserver reproducibility was calculated with kappa statistics. RESULTS: For
      thyroid cartilage, the area under the ROC curve (AUC) of the WA plus IO images
      was marginally larger than that for WA images alone (AUC=0.957 vs 0.870,
      respectively; P=.075). The specificity of WA plus IO images was significantly
      superior to that of WA images alone (96% vs 70%, respectively; P=.031), with no
      compromise to the sensitivity (86% for both). For thyroid and cricoid cartilages,
      the interobserver reproducibility was higher for diagnoses made with WA plus IO
      images (kappa=0.68-0.72 and 0.64-0.79, respectively) than for those made with WA
      images alone (kappa=0.29-0.56 and 0.20-0.64, respectively). CONCLUSION: Combined
      analysis of WA and IO images obtained with dual-energy CT improves the diagnostic
      performance and interobserver reproducibility of evaluations of laryngeal
      cartilage invasion by SCC.

PMID- 22984189
TI  - Disrupted topological organization in white matter structural networks in
      amnestic mild cognitive impairment: relationship to subtype.
AB  - PURPOSE: To investigate the topological alterations of whole-brain white matter
      structural connectivity in patients with different types of amnestic mild
      cognitive impairment (aMCI), including single-domain (SD) and multidomain (MD)
      aMCI, and to explore the relationship of such connectivity with neuropsychologic
      performance. MATERIALS AND METHODS: This study was approved by the institutional
      review board of Imaging Center for Brain Research, Beijing Normal University.
      Written informed consent was obtained from each participant. The present study
      involved 38 patients with aMCI (SD aMCI, n=18; MD aMCI, n=20) and 36 age- and sex
      matched healthy control subjects. White-matter connectional architecture in each
      participant was depicted with diffusion-weighted MR imaging and represented in
      terms of a connectivity matrix by using a deterministic tractography method.
      Graph theory-based analyses were then performed to characterize brain network
      properties. RESULTS: The global topological organization of white matter networks
      was significantly disrupted in patients with MD aMCI (P<.01 for all) but not in
      those with SD aMCI, as compared with control subjects. Connectivity impairment in
      patients with MD aMCI was found in the temporal, frontal, and parietal cortices
      (P<.05, corrected). MD aMCI had decreased network efficiency relative to SD aMCI
      (P=.016), with the most pronounced differences located in the frontal cortex
      (P<.01 for all). Strong associations between cognitive impairments and disrupted
      topological features (global, P<.05; regional, P<.002) were identified in
      patients with aMCI. CONCLUSION: The present study suggests early onset disruption
      of whole-brain white matter connectivity in patients with aMCI, especially in
      those with the MD subtype, supporting the view that MD aMCI is a more advanced
      form of disease than is SD aMCI. Moreover, cognitive correlations with
      topological network properties suggest their potential use as markers to assess
      the risk of Alzheimer disease.

PMID- 22984190
TI  - Relatives' experiences during the next of kin's hospital stay after surviving
      cardiac arrest and therapeutic hypothermia.
AB  - AIM: To describe relatives' experiences during the next of kin's hospital stay
      after surviving a cardiac arrest (CA) treated with hypothermia at an intensive
      care unit (ICU). METHODS: Twenty relatives were interviewed when the person
      having suffered the CA was discharged from hospital, 1.5 to 6 weeks post-CA. Data
      were analysed using qualitative content analysis. RESULTS: Three themes are
      described: The first period of chaos, Feeling secure in a difficult situation,
      and Living in a changed existence. Relatives found it difficult to assimilate the
      medical information and wanted it in written form. They wanted honest and clear
      information about their next of kin's condition and prognosis. They lacked
      rehabilitation plans after discharge from the medical ward. Relatives felt a need
      to maintain telephone contact with family members and friends, which was time
      consuming. They felt guilty and had a conscience about these feelings. Relatives
      felt uncertain about the future, but still hopeful. CONCLUSION: Relatives asked
      for more information and individual rehabilitation plans. Booklets describing CA,
      the ICU stay and continuing care and rehabilitation directed at both the patients
      and their relatives are needed. Follow-up visits to the ICU staff, for both
      patients and relatives, need to be arranged. Hospitals should consider having a
      rehabilitation plan for this group of patients, which is presented by a team of
      healthcare professionals and that focuses on the individual's situation,
      including the consequences of their heart disease and brain damage.

PMID- 22984191
TI  - Sperm wars and the evolution of male fertility.
AB  - Females frequently mate with several males, whose sperm then compete to fertilize
      available ova. Sperm competition represents a potent selective force that is
      expected to shape male expenditure on the ejaculate. Here, we review empirical
      data that illustrate the evolutionary consequences of sperm competition. Sperm
      competition favors the evolution of increased testes size and sperm production.
      In some species, males appear capable of adjusting the number of sperm
      ejaculated, depending on the perceived levels of sperm competition. Selection is
      also expected to act on sperm form and function, although the evidence for this
      remains equivocal. Comparative studies suggest that sperm length and swimming
      speed may increase in response to selection from sperm competition. However, the
      mechanisms driving this pattern remain unclear. Evidence that sperm length
      influences sperm swimming speed is mixed and fertilization trials performed
      across a broad range of species demonstrate inconsistent relationships between
      sperm form and function. This ambiguity may in part reflect the important role
      that seminal fluid proteins (sfps) play in affecting sperm function. There is
      good evidence that sfps are subject to selection from sperm competition, and
      recent work is pointing to an ability of males to adjust their seminal fluid
      chemistry in response to sperm competition from rival males. We argue that future
      research must consider sperm and seminal fluid components of the ejaculate as a
      functional unity. Research at the genomic level will identify the genes that
      ultimately control male fertility.

PMID- 22984193
TI  - Gastrointestinal issues and dental erosions in children.

PMID- 22984192
TI  - A comprehensive analysis of precursor microRNA cleavage by human Dicer.
AB  - Dicer cleaves double-stranded RNAs (dsRNAs) or precursor microRNAs (pre-miRNAs)
      to yield ~ 22-nt RNA duplexes. The pre-miRNA structure requirement for human
      Dicer activity is incompletely understood. By large-scale in vitro dicing assays
      and mutagenesis studies, we showed that human Dicer cleaves most, although not
      all, of the 161 tested human pre-miRNAs efficiently. The stable association of
      RNAs with Dicer, as examined by gel shift assays, appears important but is not
      sufficient for cleavage. Human Dicer tolerates remarkable structural variation in
      its pre-miRNA substrates, although the dsRNA feature in the stem region and the 2
      nt 3'-overhang structure in a pre-miRNA contribute to its binding and cleavage by
      Dicer, and a large terminal loop further enhances pre-miRNA cleavage. Dicer
      binding protects the terminal loop from digestion by S1 nuclease, suggesting that
      Dicer interacts directly with the terminal loop region.

PMID- 22984194
TI  - Parent and physician perceptions of medical home care for children with autism
      spectrum disorders in the state of Kentucky.
AB  - The medical home model of care is widely accepted as the ideal for children with
      autism spectrum disorders (ASDs) but may be very difficult to implement. In this
      study, parents of children with autism and pediatricians caring for children with
      autism in Kentucky were surveyed to determine the current status of primary care
      services for children with ASDs. Results indicated that the majority of families
      and physicians were comfortable with the routine health care provided to children
      with ASDs, but had concerns about physician ability to provide information
      regarding community resources, address comorbid conditions associated with
      autism, and discuss treatment options. The need for physician education regarding
      available national and regional autism resources is clear. Creative strategies
      involving collaboration across medical, educational, and community systems appear
      to be essential for establishing effective medical homes for children with ASDs.

PMID- 22984195
TI  - Paediatric reference values for the C-terminal fragment of fibroblast-growth
      factor-23, sclerostin, bone-specific alkaline phosphatase and isoform 5b of
      tartrate-resistant acid phosphatase.
AB  - BACKGROUND: Paediatric reference values for novel markers of phosphate
      homeostasis, bone formation and resorption and their putative relationship to
      growth are lacking. METHODS: A total of 424 healthy children, adolescents and
      young adults (221 males) aged 0.1-21 y, were enrolled in this cross-sectional
      study. Height, weight and height velocity were assessed. Plasma/serum samples for
      determination of C-terminal fragment of fibroblast growth factor-23 (cFGF-23),
      sclerostin, bone alkaline phosphatase (BAP) and tartrate-resistant acid
      phosphatase 5b (TRAP5b) were available from 222, 264, 352 and 338 individuals,
      respectively. Calculation of cross-sectional centiles and z-scores was based on
      median (M), standard coefficient of variation (S) and the Box-Cox power (L) of
      transformation (LMS method) per age cohort. Correlations between variables as
      well as with growth were assessed. RESULTS: cFGF-23, BAP and TRAP5b were
      significantly correlated with age (each P < 0.01), with highest values during
      infancy and adolescence. Serum levels of BAP and TRAP5b were significantly higher
      in adolescent boys compared with girls (each P < 0.01). In contrast, sclerostin
      levels were independent of age and gender. BAP and TRAP5b were strongly
      correlated and both were significantly associated with cFGF-23 and sclerostin as
      well (each P < 0.01). cFGF-23 was positively correlated with serum phosphate and
      renal phosphate threshold concentration (each P < 0.01). Height, weight, body
      mass index and height velocity were weakly correlated with BAP and TRAP5b (each P
      < 0.05). CONCLUSIONS: This study provides age- and gender-related centile charts
      and z-scores for cFGF-23, BAP, TRAP5b and sclerostin and highlights the link
      between phosphate homeostasis and markers of bone metabolism during growth.

PMID- 22984196
TI  - Design, development, and formative evaluation of a smartphone application for
      recording and monitoring physical activity levels: the 10,000 Steps "iStepLog".
AB  - OBJECTIVES: Limited research exists addressing the development of health-related
      smartphone apps, a new and potentially effective health promotion delivery
      strategy. This article describes the development and formative evaluation of a
      smartphone app associated with a physical activity promotion website. METHODS: A
      combination of qualitative and quantitative techniques (performance measures,
      direct observation, and subjective participant preferences) were implemented
      during two usability testing sessions (pre- and postmodification) while
      participants were completing tasks using the app. RESULTS: Design improvements to
      the app resulted in a reduction in the problems experienced and a decrease in the
      time taken to complete tasks. Four usability themes emerged from the data:
      design, feedback, navigation, and terminology. CONCLUSION: This study
      demonstrates the relevance of usability testing to the design and modification of
      a smartphone app related to a health promotion website. This study resulted in an
      app with much higher usability, which might increase usage and maintenance of
      health behavior change in the long term. PRACTICAL IMPLICATIONS: This study
      demonstrates the need for formative evaluation in health-related smartphone apps.
      Attention should be given to basic design principles as well as feedback,
      navigation, and terminology in order to ensure utility and ease of use of future
      smartphone app designs.

PMID- 22984197
TI  - Understanding breast density and breast cancer risk.

PMID- 22984198
TI  - Colonoscopy vs sigmoidoscopy: new studies fuel ongoing debate.

PMID- 22984199
TI  - Controversy trails adaptive clinical trials.

PMID- 22984200
TI  - Urology meeting highlights prostate, bladder cancers.

PMID- 22984203
TI  - Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody
      syndrome.
AB  - In the 1950s, Bickerstaff and Fisher independently described cases with a unique
      presentation of ophthalmoplegia and ataxia. The neurological features were
      typically preceded by an antecedent infection and the majority of patients made a
      spontaneous recovery. In the cases with Bickerstaff brainstem encephalitis, there
      was associated altered consciousness and in some, hyperreflexia, in support of a
      central pathology whereas in Fisher syndrome, patients were areflexic in keeping
      with a peripheral aetiology. However, both authors recognised certain
      similarities to Guillain-Barre syndrome such as the presence of peripheral
      neuropathy and cerebrospinal fluid albuminocytological dissociation. The
      discovery of immunoglobulin G anti-GQ1b antibodies in patients with Fisher
      syndrome and later in Bickerstaff brainstem encephalitis was crucial in providing
      the necessary evidence to conclude that both conditions were in fact part of the
      same spectrum of disease by virtue of their common clinical and immunological
      profiles. Following this, other neurological presentations that share anti-GQ1b
      antibodies emerged in the literature. These include acute ophthalmoparesis and
      acute ataxic neuropathy, which represent the less extensive spectrum of the
      disease whereas pharyngeal-cervical-brachial weakness and Fisher syndrome overlap
      with Guillain-Barre syndrome represent the more extensive end of the spectrum.
      The conditions can be referred to as the 'anti-GQ1b antibody syndrome'. In this
      review, we look back at the historical descriptions and describe how our
      understanding of Fisher syndrome and Bickerstaff brainstem encephalitis has
      evolved from their initial descriptions more than half a century ago.

PMID- 22984202
TI  - Protumorigenic activity of plasminogen activator inhibitor-1 through an
      antiapoptotic function.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a protease inhibitor but
      is paradoxically associated with poor outcomes in cancer patients. However, the
      mechanisms of its effects on tumor cells have not been explored. METHODS:
      Endogenous PAI-1 in human tumor cell lines (HT-1080, A549, HCT-116, and MDA-MB
      231) was suppressed by small interfering RNAs (siRNAs) and PAI-039, a small
      molecule inhibitor of PAI-1, and the effects on apoptosis were examined.
      Tumorigenicity of PAI-1 knockdown (KD) tumor cells was examined in
      immunodeficient PAI-1 wild-type and knockout (KO) mice (9-15 per group), and
      event-free survival was analyzed by the Kaplan-Meier method. The effect of PAI-1
      suppression on HT-1080 xenotransplanted tumors was evaluated for cell
      proliferation, apoptosis, and angiogenesis. All statistical tests were two-sided.
      RESULTS: Genetic and pharmacological inhibition of PAI-1 in the four tumor cell
      lines increased spontaneous apoptosis (mean fold increase relative to control: HT
      1080, siRNA#1, mean = 4.0, 95% CI = 2.6 to 5.3, P < .001; siRNA#2, mean = 2.6,
      95% CI = 2.4 to 2.9, P < .001, Student t test), which was blocked in the presence
      of recombinant PAI-1, a caspase-8 inhibitor, or Fas/FasL neutralizing antibodies
      and was partially attenuated by a plasmin inhibitor-aprotinin. PAI-1 KO mice
      implanted with PAI-1 KD HT-1080 cells had decreased tumorigenesis and prolonged
      survival compared with control mice (P = .002, log-rank test), and their tumors
      exhibited decreased cell proliferation and angiogenesis and increased apoptosis.
      Furthermore, five of 15 PAI-1 KO mice implanted with PAI-1 KD HT-1080 cells never
      developed tumors. CONCLUSIONS: These data suggest that PAI-1 exerts a protective
      effect against tumor cell apoptosis by a mechanism that, in part, involves
      plasmin activation and inhibition of Fas/Fas-L-mediated apoptosis and may be a
      promising therapeutic target.

PMID- 22984204
TI  - Comparison of 10 day bismuth quadruple therapy with high-dose metronidazole or
      levofloxacin for second-line Helicobacter pylori therapy: a randomized controlled
      trial.
AB  - OBJECTIVES: This prospective study was designed to compare the efficacies of
      levofloxacin-containing and high-dose metronidazole-containing quadruple
      therapies after failure of standard triple therapies. METHODS: A total of 150
      Helicobacter pylori-infected patients were enrolled in our study and randomly
      assigned to levofloxacin-containing quadruple therapy (EBTL group) (40 mg of
      esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg
      of tetracycline four times daily and 500 mg of levofloxacin once daily for 10
      days) (n = 76) or high-dose metronidazole-based quadruple therapy (EBTM group)
      (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times
      daily, 500 mg of tetracycline four times daily and 500 mg of metronidazole four
      times daily for 10 days) (n = 74). Follow-up endoscopy or urea breath test was
      done 16 weeks later to assess the treatment response. Patients' responses,
      CYP2C19 genotypes and antibiotic resistances were also examined. All
      participants, caregivers and those assessing the outcomes were blinded to group
      assignment. RESULTS: Intention-to-treat analysis revealed that both groups showed
      similar eradication rates: EBTL, 78.9% (60/76) (95% CI 69.7%-88.1%) and EBTM,
      79.7% (59/74) (95% CI 70.5%-88.7%) [risk ratio (RR) 0.97, 95% CI 0.44-2.14]. Per
      protocol results were EBTL = 87.0% (60/69) (95% CI 79.4%-94.9%) and EBTM = 90.8%
      (59/65) (95% CI 83.8%-97.8%) (RR 0.68, 95% CI 0.23-2.0). We did not find
      significant differences in compliance (RR 0.5, 95% CI 0.54-2.3) and adverse
      events (RR 1.11, 95% CI 0.54-2.3) between the two groups. Logistic regression
      analysis showed that only compliance was an important predictor for eradication
      failure. CYP2C19 polymorphism did not influence the eradicating effect.
      CONCLUSIONS: The 10 day bismuth quadruple therapies with high-dose metronidazole
      or levofloxacin were effective even in areas with high resistance. These two
      therapies were equally safe and tolerated. Besides this, the metronidazole
      containing therapy was cheaper. So it is persuasive that high-dose metronidazole
      containing quadruple therapy could be a good choice for second-line H. pylori
      eradication in areas with high resistance.

PMID- 22984205
TI  - Complete nucleotide sequence of pHN7A8, an F33:A-:B- type epidemic plasmid
      carrying blaCTX-M-65, fosA3 and rmtB from China.
AB  - OBJECTIVES: To characterize a representative self-transmissible multidrug
      resistance plasmid pHN7A8 isolated from an Escherichia coli from a dog in China,
      classified as F33:A-:B- by replicon sequence typing and carrying the bla(TEM-1b),
      bla(CTX-M-65), fosA3 and rmtB genes conferring resistance to penicillins,
      cephalosporins, fosfomycin and aminoglycosides, respectively. METHODS: pHN7A8 was
      sequenced using a whole-genome shotgun approach and the sequence analysed by
      comparison with reference plasmids. RESULTS: pHN7A8 is a circular molecule of 76
      878 bp. bla(CTX-M-65), fosA3 and rmtB are found in known contexts, interspersed
      with different mobile elements including ISEcp1, IS1, Tn2, IS1294, IS903 and four
      copies of IS26. This multiresistance region has only a single nucleotide
      difference from that of pXZ, an F2:A-:B- plasmid isolated from poultry in China.
      The pHN7A8 backbone carries genes encoding addiction and partitioning systems
      that promote plasmid maintenance and has a similar organization to pXZ, as well
      as IncFII plasmids such as R100, pC15-1a/pEK516 and pHK23, isolated in Japan,
      Canada/the UK and China, respectively, but with varying levels of identity,
      suggesting recombination. CONCLUSIONS: pHN7A8 is a chimera that may have resulted
      from the acquisition, by recombination in the plasmid backbone, of the
      multiresistance region found in pXZ. This region appears to have evolved from the
      resistance determinant R100 through the stepwise integration of multiple
      antimicrobial resistance determinants from different sources by the actions of
      mobile elements and recombination. The successful dissemination of this multidrug
      resistance plasmid presents further challenges for the prevention and treatment
      of Enterobacteriaceae infections.

PMID- 22984207
TI  - Are self-management interventions suitable for all? Comparing obese versus
      nonobese type 2 diabetes patients.
AB  - OBJECTIVE: The aim of the current study was to compare obese and nonobese type 2
      diabetes patients at baseline and after participating in an existing self
      management intervention (i.e., Beyond Good Intentions) on cognitive, self-care,
      and behavioral measures to examine whether both groups are equally prepared and
      able to adopt self-management approaches. METHODS: A total of 94 type 2 diabetes
      patients were included, of whom 64 (59% male) completed the study. The final
      sample consisted of 27 obese (33% male) and 37 nonobese (78% male) patients. The
      intervention comprised one individual and four group sessions and aimed to
      improve self-management behavior by enhancing proactive coping skills (i.e.,
      setting concrete goals, identifying barriers, coping with difficult situations,
      action planning, and progress evaluation). Cognitive (i.e., proactive coping,
      self-control, self-efficacy), self-care (i.e., adherence to lifestyle
      recommendations), and behavioral (i.e., diet, exercise) measures were assessed at
      baseline and after completing the intervention. RESULTS: At baseline, obese
      patients reported to possess lower cognitive skills and lower adherence to
      lifestyle recommendations compared with nonobese patients. The intervention was
      effective in improving cognitive skills, self-care activities, as well as dietary
      and exercise behaviors. Improvements were equal for obese and nonobese patients.
      However, obese patients were more likely to drop out. CONCLUSIONS: Although obese
      type 2 diabetes patients were found to possess limited skills at baseline
      compared with nonobese patients, the self-management course proved to be equally
      effective for both groups.

PMID- 22984206
TI  - Response to raltegravir-based salvage therapy in HIV-infected patients with
      hepatitis C virus or hepatitis B virus coinfection.
AB  - OBJECTIVES: To define the impact of coinfection with hepatitis B virus (HBV) or
      hepatitis C virus (HCV) on viroimmunological response to raltegravir-based
      salvage regimens that also include new HIV inhibitors such as maraviroc,
      darunavir and etravirine. METHODS: We used data from a national observational
      study of patients starting raltegravir-based regimens to compare virological
      suppression and CD4 cell change from baseline in patients with and without
      concomitant HBV or HCV infection. RESULTS: Overall, 275 patients (107 coinfected
      and 168 non-coinfected) were evaluated. Coinfected patients were more commonly
      former intravenous drug users and had a longer history of HIV infection and
      higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were
      similar in the two groups. Mean time to first HIV-RNA copy number <50 copies/mL
      was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI
      3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P =
      0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse
      events was significantly higher in coinfected patients (hazard ratio 1.779, 95%
      CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected
      patients had similar rates of interruption of any baseline drug (hazard ratio
      1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95%
      CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred.
      CONCLUSIONS: Viroimmunological response to regimens based on raltegravir and
      other recent anti-HIV inhibitors is not negatively affected by coinfection with
      HBV or HCV. Liver toxicity, either pre-existing or new, is more common in
      coinfected patients, but with no increased risk of treatment interruption.

PMID- 22984208
TI  - A test of the theory of planned behavior to predict physical activity in an
      overweight/obese population sample of adolescents from Alberta, Canada.
AB  - PURPOSE: To examine the utility of the theory of planned behavior (TPB) for
      explaining physical activity (PA) intention and behavior among a large population
      sample of overweight and obese adolescents (Alberta, Canada), using a web-based
      survey. Secondary objectives were to examine the mediating effects of the TPB
      constructs and moderating effects of weight status. METHODS: A subsample of 427
      overweight and 133 obese participants (n = 560), completed a self-administered
      web-based questionnaire on health and PA behaviors, including assessment of
      attitude, subjective norm, perceived behavioral control (PBC), and intention to
      participate in regular PA. Structural equation models were examined using AMOS
      17.0. RESULTS: Overall, 62% of the variance in intention was accounted for by
      attitude, subjective norm, and PBC; whereas 44% of the variance in PA behavior
      was explained by PBC and intention. When examining the TPB separately in
      overweight and obese subsamples, 66% and 56% of the variance for PA intention was
      explained for overweight and obese subsamples, respectively; and 38% and 56% of
      the variance in PA behavior were accounted for in the overweight and obese
      subsamples. Overall, attitude was the strongest predictor of PA intention,
      whereas PBC was the strongest predictor for PA behavior. Intention was not
      predictive of PA behavior. CONCLUSIONS: These results provide partial support for
      the utility of TPB in explaining PA behavior in a sample of overweight and obese
      adolescents. In particular, strong associations regarding attitude and PBC were
      evident across each subsample. These findings have implications for tailoring PA
      programs in this population.

PMID- 22984209
TI  - A cross-cultural comparison of sleep duration between US And Australian
      adolescents: the effect of school start time, parent-set bedtimes, and
      extracurricular load.
AB  - STUDY OBJECTIVE: To test whether sleep duration on school nights differs between
      adolescents in Australia and the United States and, if so, whether this
      difference is explained by cultural differences in school start time, parental
      involvement in setting bedtimes, and extracurricular commitments. PARTICIPANTS:
      Three hundred eighty-five adolescents aged 13 to 18 years (M = 15.57, SD = 0.95;
      60% male) from Australia and 302 adolescents aged 13 to 19 years (M = 16.03, SD =
      1.19; 35% male) from the United States. METHODS: Adolescents completed the School
      Sleep Habits Survey during class time, followed by an 8-day sleep diary. RESULTS:
      After controlling for age and gender, Australian adolescents obtained an average
      of 47 minutes more sleep per school night than those in the United States.
      Australian adolescents were more likely to have a parent-set bedtime (17.5% vs.
      6.8%), have a later school start time (8:32 a.m. vs. 7:45 a.m.), and spend less
      time per day on extracurricular commitments (1 h 37 min vs. 2 h 41 min) than
      their U.S. peers. The mediating factors of parent-set bedtimes, later school
      start times, and less time spent on extracurricular activities were significantly
      associated with more total sleep. CONCLUSIONS: In addition to biological factors,
      extrinsic cultural factors significantly affect adolescent sleep. The present
      study highlights the importance of a cross-cultural, ecological approach and the
      impact of early school start times, lack of parental limit setting around
      bedtimes, and extracurricular load in limiting adolescent sleep.

PMID- 22984210
TI  - Exploring patient activation in the clinic: measurement from three perspectives.
AB  - OBJECTIVE: To further conceptualize and operationalize patient activation (PA),
      using measures from patient, physician, and researcher perspectives. DATA
      SOURCE/STUDY SETTING: Multimethod observation in 2010 within a family medicine
      clinic. STUDY DESIGN: Part of an intervention with 130 patients with type 2
      diabetes, this observational study further looked at PA in 19 physician-patient
      dyads. Data Collection. Observations occurred in a teaching hospital, which
      served as recruiting and study site. PRINCIPAL FINDINGS: PA correlated with
      knowledge, self-efficacy, promotion orientation, and exercise intent. Patient
      reported PA did not correlate with researcher-observed or physician-reported PA
      behavior. Researcher-observed PA correlated with physician-observation items.
      CONCLUSIONS: Results provide evidence for measuring different perspectives in
      studies of PA. When patients report they are activated in self-management,
      behavior does not indicate they are active in clinical communication, a critical
      component of collaborative decision making.

PMID- 22984211
TI  - Examining the longitudinal relationship between change in sleep and obesity risk
      in adolescents.
AB  - Evidence is building regarding the association between inadequate amounts of
      sleep and the risk of obesity, especially in younger children. Less is known
      about the relationship between change in sleep and change in weight during
      adolescence. The objective of this study was to examine the longitudinal
      relationship between change in sleep duration and change in body mass index (BMI)
      and percent body fat (PBF) in a cohort of adolescents. The cohort included 723
      adolescents (mean age = 14.7 years at baseline) from Minnesota. Total sleep
      duration was assessed via self-report. BMI and PBF were objectively assessed.
      Covariates used in the multivariate analyses included energy intake as assessed
      through 24-hour recalls, activity levels as assessed by accelerometers, screen
      time/sedentary behavior, depression, and sociodemographic characteristics. For
      both males and females, average BMI and PBF increased slightly over the 2 years
      and average sleep duration decreased by about 30 minutes. The authors saw no
      statistically significant longitudinal relationships between change in total
      sleep and change in BMI or PBF over time in either girls or boys. The only
      longitudinal relationship that approached statistical significance was a positive
      association between sleep and PBF in females (p = .068). This research
      contributes to the literature as the only study to date to examine how change in
      sleep duration during adolescence may be related to a concomitant change in BMI
      and body fat. The findings of this study do not support the hypothesis that a
      decline in sleep duration during adolescence increases obesity risk.

PMID- 22984213
TI  - Connecting the dots of a public health career.

PMID- 22984212
TI  - Promoting patient phronesis: communication patterns in an online lifestyle
      program coordinated with primary care.
AB  - Phronesis, or practical wisdom developed through experience, is an Aristotelian
      concept that can shed light on the capacities of patients to make health-related
      decisions and engage in healthy behaviors. In this article, the authors develop a
      conceptual framework for understanding the role of phronesis in lifestyle change
      as well as its relationship to patient activation, which is considered to be a
      critical component of the Chronic Care Model and patient education in general.
      The authors develop the concept of phronesis by analyzing qualitatively the
      comments made by 35 participants working to manage chronic health issues in a
      weight-loss study. The authors iteratively coded transcribed passages of exit
      interviews for phronesis and patient activation. These passages provide
      experientially grounded content for evaluating the use of phronesis and its
      development among individuals engaging in lifestyle change. Phronesis is
      expressed in 31% of participant responses to questions regarding the relationship
      between the online lifestyle intervention, participant health, and participant
      readiness to engage in productive clinical encounters with health care
      practitioners. Of those responses, 73% express some level of patient activation.
      The authors conclude that phronesis may be an important new tool for
      understanding successful self-management support, with potential usefulness in
      the creation of tailored lifestyle interventions, the development of patient
      activation, and the ability of participants to enact health-related behaviors.

PMID- 22984214
TI  - Approaches to increase arsenic awareness in Bangladesh: an evaluation of an
      arsenic education program.
AB  - The objective of this study was to design and evaluate a household-level arsenic
      education and well water arsenic testing intervention to increase arsenic
      awareness in Bangladesh. The authors randomly selected 1,000 study respondents
      located in 20 villages in Singair, Bangladesh. The main outcome was the change in
      knowledge of arsenic from baseline to follow-up 4 to 6 months after the household
      received the intervention. This was assessed through a pre- and postintervention
      quiz concerning knowledge of arsenic. Respondents were between 18 and 102 years
      of age, with an average age of 37 years; 99.9% were female. The knowledge of
      arsenic quiz scores for study participants were significantly higher at follow-up
      compared with baseline. The intervention was effective in increasing awareness of
      the safe uses of arsenic-contaminated water and dispelling the misconception that
      boiling water removes arsenic. At follow-up, nearly all respondents were able to
      correctly identify the meaning of a red (contaminated) and green (arsenic safe)
      well relative to arsenic (99%). The educational program also significantly
      increased the proportion of respondents who were able to correctly identify the
      health implications of arsenic exposure. However, the intervention was not
      effective in dispelling the misconceptions in the population that arsenicosis is
      contagious and that illnesses such as cholera, diarrhea, and vomiting could be
      caused by arsenic. Further research is needed to develop effective communication
      strategies to dispel these misconceptions. This study demonstrates that a
      household-level arsenic educational program can be used to significantly increase
      arsenic awareness in Bangladesh.

PMID- 22984215
TI  - What makes or breaks provider-researcher collaborations in HIV research? A mixed
      method analysis of providers' willingness to partner.
AB  - Research is lacking about what makes or breaks collaboration between researchers
      and HIV services providers. This study identified factors that influence
      providers' levels of willingness to collaborate in HIV prevention scientific
      research. Survey measures were grounded in in-depth interview data and included
      providers' "willingness to collaborate," and providers' attitudes toward
      researchers' availability, benefits of research, and agency preparedness. This
      survey was administered to 141 providers in New York City. A hierarchical
      regression model showed that providers' perceptions of researchers' availability
      (p < .05), research benefits (p < .001), and agency preparedness (p < .05) were
      associated with providers' willingness to engage with researchers to purse HIV
      prevention research. Findings indicate that researchers need to be socially and
      professionally available, future HIV research should benefit providers and
      consumers, and policy makers should help agency settings develop human and
      financial resources in preparation for research.

PMID- 22984216
TI  - Unity in diversity: results of a randomized clinical culturally tailored pilot
      HIV prevention intervention trial in Baltimore, Maryland, for African American
      men who have sex with men.
AB  - Unity in Diversity was a randomized controlled trial of a culturally tailored HIV
      prevention intervention for African American men who have sex with men. The
      intervention condition was six group-based sessions and one individual session.
      The control condition was a single-session HIV prevention review. Participants
      were aged 18 years or older, identified as African American/Black race, reported
      having at least two sex partners in the prior 90 days (at least one of whom must
      be a male partner), unprotected anal sex with male partner in the prior 90 days,
      and willing to test for HIV. Retention exceeded 95% at 3-month follow-up. Results
      of multivariate logistic regression analysis adjusting for baseline risk, HIV
      status, and health insurance indicate intervention efficacy in decreasing the
      number of male sex partners and marginal effects on condom use with male partners
      and HIV-negative/unknown partners. Specifically, intervention condition was
      associated with increased odds of zero male sex partners (adjusted odds ratio
      [AOR] = 3.03, 95% confidence interval [CI] = 1.26-7.28), condom use with male
      partners (AOR = 2.64, 95% CI = 0.95-7.36), and HIV-negative/unknown status
      partners (AOR = 3.19, 95% CI = 0.98-10.38) at follow-up. These results contribute
      to the limited number of culturally appropriate models of HIV prevention
      intervention that are urgently needed for African American men who have sex with
      men to address their persistently high rates of HIV.

PMID- 22984217
TI  - Nondisclosure of smoking status to health care providers among current and former
      smokers in the United States.
AB  - An unintended consequence of tobacco control's success in marginalizing smoking
      is that smokers may conceal their smoking from those who are best positioned to
      help them quit: health care providers (HCPs). The purpose of this study was to
      identify the prevalence of, and factors related to, nondisclosure of smoking to
      HCPs. Data were obtained from a cross-sectional survey of adults from a
      nationally representative Knowledge Networks online panel in March to April 2011.
      Current and former smokers (n = 2,803) were asked questions about nondisclosure,
      tobacco use, cessation behavior, and perceived social unacceptability of smoking.
      All variables significantly related (p < .05) to nondisclosure in bivariate
      logistic regression were included in the multivariate logistic regression model,
      which also adjusted for gender, age, race, marital status, and education.
      Approximately 1 in 10 smokers (12.9%) and 5.8% of former smokers has withheld
      their smoking status from HCPs. Ever smokers who were 18 to 34 years, those who
      had used a prescription medication or behavioral therapy in their last quit
      attempt, and those who were uncomfortable discussing smoking with their HCP were
      more likely to report nondisclosure than those in their respective comparison
      groups. Respondents who perceived either medium or high smoker-related stigma
      (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.05, 2.77 and OR = 2.60,
      95% CI = 1.51, 4.48, respectively) and those who reported concealing smoking to
      gain benefits from health insurance were also significantly more likely to have
      kept smoking a secret from an HCP (OR = 5.66, 95% CI = 1.88, 17.02). Smokers
      should be encouraged to be forthright about their smoking in order for
      practitioners to offer treatment and services that increase their chances of
      quitting.

PMID- 22984219
TI  - Sex and SUVmax: sex-dependent prognostication in early non-small cell lung
      cancer.
AB  - The identification of robust prognostic factors for patients with early-stage non
      small cell lung cancer (NSCLC) is clinically important. The International
      Association for the Study of Lung Cancer has identified both sex and the maximum
      standardized uptake value (SUVmax) of (18)F-FDG in the primary tumor as measured
      by PET as potential prognostic variables. We examined the prognostic value of
      SUVmax in a surgical cohort of patients with NSCLC and disaggregated the findings
      by sex. METHODS: Patients who had undergone a preoperative PET/CT scan and
      surgical resection with curative intent from 2001 to 2009 were identified from a
      prospective database. An SUVmax cutoff was calculated using receiver-operating
      characteristic curves. Overall survival was correlated with SUVmax for the whole
      cohort and disaggregated by sex. RESULTS: Inclusion criteria were met by 189
      patients: 127 (67%) men and 62 (33%) women. Five-year survival was 54.6% for the
      whole cohort, 47.7% for men, and 68.2% for women. SUVmax correlated negatively
      with survival in a univariate analysis for the whole cohort (hazard ratio [HR],
      2.51; 95% confidence interval [CI], 1.54-4.09; P < 0.001) and men (HR, 3.42; 95%
      CI, 1.94-6.05; P < 0.001) but not for women (HR, 1.61; 95% CI, 0.43-3.12; P =
      0.77), using 8 as a cutoff. In multivariate analysis, SUVmax correlated with
      overall survival for the whole cohort (HR, 1.70; 95% CI, 1.05-2.99; P = 0.05) and
      men (HR, 2.40; 95% CI, 1.32-4.37; P = 0.004) but not for women (HR, 0.80; 95% CI,
      0.15-4.47; P = 0.80). CONCLUSION: SUVmax independently predicted overall survival
      for men but not for women in this surgical cohort. Our results suggest that
      SUVmax is an independent prognostic variable in men with surgically treated early
      NSCLC.

PMID- 22984218
TI  - Multitargeted tyrosine kinase inhibition produces discordant changes between
      99mTc-MDP bone scans and other disease biomarkers: analysis of a phase II study
      of sunitinib for metastatic castration-resistant prostate cancer.
AB  - One of the central unanswered questions in prostate cancer research is the
      significance of tyrosine kinase inhibitor (TKI)-induced improvements in (99m)Tc
      methylene diphosphonate ((99m)Tc-MDP) bone scans. Multitargeted tyrosine kinase
      inhibition has recently shown promise in the management of castration-resistant
      prostate cancer. In some cases, TKI inhibition has produced unprecedented
      improvements in bone metastases as detected by (99m)Tc-MDP bone scans. The
      significance of these improvements is not known. In order to gain insight about
      the effects of TKIs on bone scans in prostate cancer, we systematically evaluated
      images from a phase II study of sunitinib, a multitargeted TKI. METHODS: We
      analyzed images and data from a previously reported open-label phase II study
      that enrolled 34 men with advanced castration-resistant prostate cancer.
      Participants received sunitinib in 6-wk cycles (50 mg daily; 4 wk on, 2 wk off).
      We examined baseline and 12-wk bone scan images. Partial response was defined as
      an improvement of at least 50% in previous metastatic lesions subjectively or a
      change from prior diffuse skeletal metastases (superscan) to recognizable
      individual metastatic lesions. Our primary objective was to define the incidence
      of at least partial bone scan response. We also examined concomitant changes in
      CT and prostate-specific antigen (PSA) evidence of disease. RESULTS: Analysis at
      12 wk revealed 1 partial response by the response evaluation criteria in solid
      tumors (RECIST) and 2 confirmed PSA responses. There were 25 subjects who
      underwent bone scans at both time points (baseline and week 12) and who had bone
      metastases detectable at baseline. Within that group of 25, we found 5 bone scan
      partial responses and 1 complete response. None of those 6 subjects exhibited a
      PSA response (>=50% decline from baseline) or RECIST response. CONCLUSION: We
      found a relatively high rate of (99m)Tc-MDP bone scan response to sunitinib among
      men with metastatic prostate cancer. Further, we found that none of the subjects
      exhibiting bone scan responses experienced concordant improvements in PSA or CT
      evidence of disease by accepted criteria. This discordance argues that
      osteoblastic assessment provides an incomplete assessment of treatment-induced
      changes. Rational development of multitargeted TKIs for prostate cancer requires
      improved understanding of treatment-induced bone scan changes. Optimal imaging
      strategies may include evaluation of perfusion or direct tumor activity.

PMID- 22984220
TI  - The role of 68Ga-DOTATATE PET/CT in suspected neuroendocrine tumors.
AB  - In patients with suspected but yet not localized neuroendocrine tumors (NETs),
      early diagnosis or reliable exclusion is crucial for optimal individual prognosis
      and therapy. Despite recourse to several imaging modalities, the definite
      diagnosis of NET can be challenging. Therefore, we tested (68)Ga-DOTATATE PET/CT
      as a tool for improved diagnosis in a cohort of patients with suspected,
      nonlocalized NET. METHODS: (68)Ga-DOTATATE PET/CT recordings were obtained in 104
      consecutive patients meeting at least one of the following criteria: clinical
      suspicion of NET (n = 70), elevated blood levels of tumor markers (n = 49), and
      image-based suspicion of NET (n = 53). The presence of NET was validated by
      histopathology (n = 49) or clinical follow-up of 107 +/- 59 wk (n = 55). RESULTS:
      In 36 of 104 patients (35%), NET was histologically verified, most frequently
      located in the small bowel (10/36), pancreas (8/36), lung (5/36), and stomach
      (2/36). Twelve patients had tumors of nonneuroendocrine origin, and 7 patients
      had benign tumors. (68)Ga-DOTATATE PET/CT identified NET in 29 of the 36 cases
      and excluded the presence of a NET in 61 of the 68 non-NET patients, indicating a
      sensitivity of 81% and specificity of 90%. The PET/CT gave a false-positive
      result in 7 patients and a false-negative in another 7 patients, indicating
      positive and negative predictive values of 81% and 90%, respectively, and an
      accuracy of 87%. Chromogranin A levels were significantly higher in both PET
      positive patients (1,841 vs. 342 ng/mL; P < 0.05) and patients with verified NET
      (2,214 vs. 524 ng/mL; P < 0.05). CONCLUSION: In patients with suspected NETs due
      to clinical symptoms, elevated levels of tumor markers, or indeterminate tumors
      suggestive of NET, (68)Ga-DOTATATE PET/CT is highly accurate, thus supporting its
      use in clinical routine diagnostics.

PMID- 22984221
TI  - Black-white asymmetry in visual perception.
AB  - With eleven different types of stimuli that exercise a wide gamut of spatial and
      temporal visual processes, negative perturbations from mean luminance are found
      to be typically 25% more effective visually than positive perturbations of the
      same magnitude (range 8-67%). In Experiment 12, the magnitude of the black-white
      asymmetry is shown to be a saturating function of stimulus contrast. Experiment
      13 shows black-white asymmetry primarily involves a nonlinearity in the visual
      representation of decrements. Black-white asymmetry in early visual processing
      produces even-harmonic distortion frequencies in all ordinary stimuli and in
      illusions such as the perceived asymmetry of optically perfect sine wave
      gratings. In stimuli intended to stimulate exclusively second-order processing in
      which motion or shape are defined not by luminance differences but by differences
      in texture contrast, the black-white asymmetry typically generates artifactual
      luminance (first-order) motion and shape components. Because black-white
      asymmetry pervades psychophysical and neurophysiological procedures that utilize
      spatial or temporal variations of luminance, it frequently needs to be considered
      in the design and evaluation of experiments that involve visual stimuli. Simple
      procedures to compensate for black-white asymmetry are proposed.

PMID- 22984222
TI  - Optimal edge filters explain human blur detection.
AB  - Edges are important visual features, providing many cues to the three-dimensional
      structure of the world. One of these cues is edge blur. Sharp edges tend to be
      caused by object boundaries, while blurred edges indicate shadows, surface
      curvature, or defocus due to relative depth. Edge blur also drives accommodation
      and may be implicated in the correct development of the eye's optical power. Here
      we use classification image techniques to reveal the mechanisms underlying blur
      detection in human vision. Observers were shown a sharp and a blurred edge in
      white noise and had to identify the blurred edge. The resultant smoothed
      classification image derived from these experiments was similar to a derivative
      of a Gaussian filter. We also fitted a number of edge detection models (MIRAGE,
      N(1), and N(3)(+)) and the ideal observer to observer responses, but none
      performed as well as the classification image. However, observer responses were
      well fitted by a recently developed optimal edge detector model, coupled with a
      Bayesian prior on the expected blurs in the stimulus. This model outperformed the
      classification image when performance was measured by the Akaike Information
      Criterion. This result strongly suggests that humans use optimal edge detection
      filters to detect edges and encode their blur.

PMID- 22984223
TI  - The effect of perceptual grouping on perisaccadic spatial distortions.
AB  - Perisaccadic spatial distortion (PSD) occurs when a target is flashed immediately
      before the onset of a saccade and it appears displaced in the direction of the
      saccade. In previous studies, the magnitude of PSD of a single target was
      affected by multiple experimental parameters, such as the target's luminance and
      its position relative to the central fixation target. Here we describe a
      contextual effect in which the magnitude of the PSD for a target was influenced
      by the synchronous presentation of another target: PSD for simultaneously
      presented targets was more uniform than when each was presented individually.
      Perisaccadic compression was ruled out as a causal factor, and the results
      suggest that both low- and high-level perceptual grouping mechanisms may account
      for the change in PSD magnitude. We speculate that perceptual grouping could play
      a key role in preserving shape constancy during saccadic eye movements.

PMID- 22984224
TI  - Change in visual acuity is highly correlated with change in six image quality
      metrics independent of wavefront error and/or pupil diameter.
AB  - It is well known that the wavefront error (WFE) of the eye varies from individual
      to individual with pupil diameter (PD) and age. Numerous studies have been
      proposed evaluating the relationship between visual acuity and WFE, but all these
      studies were performed with either a fixed or natural PD. It is still not clear
      if metrics of image quality correlate well with visual acuity independent of PD.
      Here we investigate the correlation between the change in visual acuity and the
      change in 30 image quality metrics for a range of optical quality typically
      established in normal eyes that varies both with age and PD. Visual acuity was
      recorded for 4 normal subjects using simulated blurred logMAR acuity charts
      generated from the point spread functions of different scaled WFEs for 6
      different PDs (2-7 mm in 1 mm steps). Six image quality metrics (log neural
      sharpness, log visual Strehl [spatial domain], log visual Strehl [MTF method],
      log pupil fraction [tessellated], log pupil fraction [concentric area], and log
      root mean square of WFE slope) accounted for over 80% of variance in change in
      acuity across all WFEs and all PDs. Multiple regression analysis did not
      significantly increase the R(2). Simple metrics derived from WFE could
      potentially act as an objective surrogate to visual acuity without the need for
      complex models.

PMID- 22984225
TI  - Identification and functional characterization of a novel UDP
      glucuronosyltransferase 2A1 splice variant: potential importance in tobacco
      related cancer susceptibility.
AB  - UDP-glucuronosyltransferase (UGT) 2A1 is a respiratory and aerodigestive tract
      expressing phase II detoxifying enzyme that metabolizes various xenobiotics
      including polycyclic aromatic hydrocarbons (PAHs). In the present study, a novel
      exon 3 deletion splice variant was identified for UGT2A1 (UGT2A1Deltaexon3). As
      determined by reverse transcription-polymerase chain reaction (PCR),
      UGT2A1Deltaexon3 was shown to be expressed in various tissues including lung,
      trachea, larynx, tonsil, and colon. The ratio of UGT2A1Deltaexon3/wild-type
      UGT2A1 expression was highest in colon (0.79 +/- 0.08) and lung (0.42 +/- 0.12)
      as determined by real-time PCR; an antibody specific to UGT2A1 showed splice
      variant protein (UGT2A1_i2) to wild-type protein (UGT2A1_i1) ratios in the range
      of 0.5 to 0.9 in these tissues. Using ultra-pressure liquid chromatography, we
      found that homogenates prepared from UGT2A1_i2-overexpressing human embryonic
      kidney 293 cells exhibited no glucuronidation activity against PAHs, including
      benzo[a]pyrene-7,8-dihydrodiol (B[a]P-7,8-diol). An inducible in vitro system was
      created to determine the effect of UGT2A1_i2 expression on UGT2A1_i1 activity.
      Increasing UGT2A1_i2 levels resulted in a significant (p < 0.01) decrease in the
      UGT2A1_i1 V(max) against 1-hydroxy (OH)-pyrene, 3-OH-benzo[a]pyrene, and B[a]P
      7,8-diol; no significant changes in K(M) were observed for any of the three
      substrates. Coimmunoprecipitation experiments suggested the formation of
      UGT2A1_i1 and UGT2A1_i2 hetero-oligomers and UGT2A1_i1 homo-oligomers;
      coexpression of UGT2A1_i1 or UGT2A1_i2 with other UGT1A or UGT2B enzymes caused
      no change in UGT1A or UGT2B glucuronidation activity. These data suggest that a
      novel UGT2A1 splice variant regulates UGT2A1-mediated glucuronidation activity
      via UGT2A1-specific protein-protein interactions, and expression of this variant
      could play an important role in the detoxification of carcinogens within target
      tissues for tobacco carcinogenesis.

PMID- 22984226
TI  - Novel antiplatelet activity of protocatechuic acid through the inhibition of high
      shear stress-induced platelet aggregation.
AB  - Bleeding is the most common and serious adverse effect of currently available
      antiplatelet drugs. Many efforts are being made to develop novel antithrombotic
      agents without bleeding risks. Shear stress-induced platelet aggregation (SIPA),
      which occurs under abnormally high shear stress, plays a crucial role in the
      development of arterial thrombotic diseases. Here, we demonstrate that
      protocatechuic acid (PCA), a bioactive phytochemical from Lonicera (honeysuckle)
      flowers, selectively and potently inhibits high shear (>10,000 s(-1))-induced
      platelet aggregation. In isolated human platelets, PCA decreased SIPA and
      attenuated accompanying platelet activation, including intracellular calcium
      mobilization, granule secretion, and adhesion receptor expression. The anti-SIPA
      effect of PCA was mediated through blockade of von Willebrand factor binding to
      activated glycoprotein Ib, a primary and initial event for the accomplishment of
      SIPA. Conspicuously, PCA did not inhibit platelet aggregation induced by other
      endogenous agonists like collagen, thrombin, or ADP that are important in both
      pathological thrombosis and normal hemostasis. Antithrombotic effects of PCA were
      confirmed in vivo in a rat arterial thrombosis model, where PCA significantly
      delayed the arterial occlusion induced by FeCl(3). Of particular note, PCA did
      not increase bleeding times in a rat tail transection model, whereas conventional
      antiplatelet drugs, aspirin, and clopidogrel substantially prolonged it.
      Collectively, these results suggest that PCA may be a novel antiplatelet agent
      that can prevent thrombosis without increasing bleeding risks.

PMID- 22984228
TI  - Update on Advisory Committee on Immunization Practices (ACIP) Vaccine
      Recommendations, June 2012.

PMID- 22984229
TI  - Need to OPPOSE PROPOSED ACGME Common Program Requirements.

PMID- 22984227
TI  - Dendritic spine injury induced by the 8-hydroxy metabolite of efavirenz.
AB  - Despite combination antiretroviral therapies (cARTs), a significant proportion of
      HIV-infected patients develop HIV-associated neurocognitive disorders (HAND).
      Ongoing viral replication in the central nervous system (CNS) caused by poor
      brain penetration of cART may contribute to HAND. However, it has also been
      proposed that the toxic effects of long-term cART may contribute to HAND. A
      better understanding of the neurotoxic potential of cART is critically needed in
      light of the use of CNS-penetrating cARTs to contend with the virus reservoir in
      the brain. The efavirenz (EFV) metabolites 7-hydroxyefavirenz (7-OH-EFV) and 8
      hydroxyefavirenz (8-OH-EFV) were synthesized and purified, and their chemical
      structures were confirmed by mass spectrometry and NMR. The effects of EFV, 7-OH
      EFV, and 8-OH-EFV on calcium, dendritic spine morphology, and survival were
      determined in primary neurons. EFV, 7-OH-EFV, and 8-OH-EFV each induced neuronal
      damage in a dose-dependent manner. However, 8-OH-EFV was at least an order of
      magnitude more toxic than EFV or 7-OH-EFV, inducing considerable damage to
      dendritic spines at a 10 nM concentration. The 8-OH-EFV metabolite evoked calcium
      flux in neurons, which was mediated primarily by L-type voltage-operated calcium
      channels (VOCCs). Blockade of L-type VOCCs protected dendritic spines from 8-OH
      EFV-induced damage. Concentrations of EFV and 8-OH-EFV in the cerebral spinal
      fluid of HIV-infected subjects taking EFV were within the range that damaged
      neurons in culture. These findings demonstrate that the 8-OH metabolite of EFV is
      a potent neurotoxin and highlight the importance of directly determining the
      effects of antiretroviral drugs and drug metabolites on neurons and other brain
      cells.

PMID- 22984230
TI  - Paradoxical hyponatremia and polyurodipsia in a patient with lithium-induced
      nephrogenic diabetes insipidus.

PMID- 22984231
TI  - Advancing osteopathic medicine through research.

PMID- 22984232
TI  - Using manual and conventional therapies to enhance musculoskeletal health:
      highlights of the Osteopathic Research Center's 10th Anniversary Conference.

PMID- 22984233
TI  - Associations of cytokine concentrations with key osteopathic lesions and clinical
      outcomes in patients with nonspecific chronic low back pain: results from the
      OSTEOPATHIC Trial.
AB  - CONTEXT: Little is known about the role that cytokines play in osteopathic manual
      treatment (OMT) of patients with chronic low back pain (LBP). OBJECTIVE: To
      measure the baseline concentrations of interleukin (IL)-1beta, IL-6, IL-8, IL-10,
      and tumor necrosis factor (TNF)-alpha in patients with chronic LBP; the
      correlations of these cytokine concentrations with clinical measures, including
      the number of key osteopathic lesions; the changes in cytokine concentrations
      with OMT; and the association of such changes with clinical outcomes. DESIGN:
      Substudy nested within a randomized controlled trial of OMT for nonspecific
      chronic LBP. SETTING: University-based study in Dallas-Fort Worth, Texas.
      PATIENTS: Seventy adult research patients with nonspecific chronic LBP. MAIN
      OUTCOME MEASURES: A 10-cm visual analog scale, the Roland-Morris Disability
      Questionnaire, and the Medical Outcomes Study Short Form-36 Health Survey were
      used to measure LBP severity, back-specific functioning, and general health,
      respectively. RESULTS: At baseline, IL-1beta (rho = 0.33; P = .005) and IL-6 (rho
      = 0.32; P = .006) were each correlated with the number of key osteopathic
      lesions; however, only IL-6 was correlated with LBP severity (rho = 0.28; P =
      .02). There was a significantly greater reduction of TNF-alpha concentration
      after 12 weeks in patients who received OMT compared with patients who received
      sham OMT (Mann-Whitney U = 251.5; P = .03). Significant associations were found
      between OMT and a reduced TNF-alpha concentration response at week 12 among
      patients who achieved moderate (response ratio, 2.13; 95% confidence interval
      [CI], 1.11-4.06; P = .006) and substantial (response ratio, 2.13; 95% CI, 1.07
      4.25; P = .01) LBP improvements, and improvement in back-specific functioning
      (response ratio, 1.68; 95% CI, 1.04-2.71; P = .03). CONCLUSIONS: This study found
      associations between IL-1beta and IL-6 concentrations and the number of key
      osteopathic lesions and between IL-6 and LBP severity at baseline. However, only
      TNF-alpha concentration changed significantly after 12 weeks in response to OMT.
      These discordant findings indicate that additional research is needed to
      elucidate the underlying mechanisms of action of OMT in patients with nonspecific
      chronic LBP.

PMID- 22984234
TI  - Precompetition manipulative treatment and performance among Virginia Tech
      athletes during 2 consecutive football seasons: a preliminary, retrospective
      report.
AB  - CONTEXT: One of the goals of providing manipulative treatment such as osteopathic
      manipulative treatment (OMT) is to restore maximal, pain-free movement of the
      musculoskeletal system and to enhance neuromuscular function. Anecdotally, some
      athletes have reported that their athletic performance improves after
      manipulative treatment. OBJECTIVE: To develop preliminary data to gain more
      understanding about the association between precompetition manipulative
      treatments provided to Division I football players and their athletic performance
      during each game for 2 consecutive football seasons. METHODS: The study design
      was a retrospective cohort study. Participants were football athletes at Virginia
      Polytechnic Institute and State University (Virginia Tech). Board-certified
      osteopathic physicians who were trained in osteopathic manipulative medicine and
      sports medicine performed OMT and determined the type of OMT techniques used and
      the spinal segments treated. One chiropractor provided chiropractic manipulative
      therapy. Prior to each game, the athletes who elected to receive precompetition
      manipulative treatment (ie, OMT or chiropractic manipulative therapy) underwent a
      focused physical examination and received manipulative treatment on the basis of
      clinical findings. After each game, the coaching staff "graded" the players by
      using a standard coaching algorithm. Offensive players received a percentile
      score (0 to 100) and defensive players received a numeric score (> 30 was
      considered "very good"). RESULTS: A total of 1976 manipulative treatments were
      provided to 115 football players in 2 consecutive football seasons. Sixty-two
      offensive players received 985 manipulative treatments, and 53 defensive players
      received 991 manipulative treatments. Treatments were applied to the affected
      regions of the spine: cervical, thoracic, lumbar, and sacral sections. Mean
      (standard deviation) performance scores were 67.8% (22.8%) and 11.1 (9.9) points
      among offensive and defensive players, respectively. The correlation coefficients
      between the numbers of the manipulative treatments and the performance scores
      were 0.107 (P = .407) among the offensive players and 0.218 (P=.117) among the
      defensive players. CONCLUSION: Precompetition manipulative treatment was
      positively associated with improved performance among both offensive and
      defensive Virginia Tech football players. Although the associations between these
      2 factors were relatively small and not statistically significant, we found
      positive correlations in performance of the offensive and defensive players.

PMID- 22984235
TI  - The biology of manual therapies.
AB  - Each year, more than 18 million adults in the United States receive manual
      therapies, at a total annual out-of-pocket cost of $3.9 billion. Although there
      is growing evidence supporting the efficacy of manual therapies, little is known
      about the mechanisms underlying these treatments. This lack of basic knowledge
      significantly limits the development of rational strategies for the use of these
      treatments and potentially hinders their acceptance by the wider scientific and
      health care communities. Many authors have hypothesized that manual therapies act
      by disrupting the pain-spasm-pain cycle, but relatively little experimental
      evidence has supported this hypothesis. The authors have tested this hypothesis
      and summarize their work on the biology of manual therapies.

PMID- 22984236
TI  - Babesiosis in Westchester County, New York.

PMID- 22984237
TI  - Just throw me to the lions.

PMID- 22984238
TI  - Beware of the venous return in cardiovascular control.

PMID- 22984243
TI  - Heterogeneous atrophy occurs within individual lower limb muscles during 60 days
      of bed rest.
AB  - To better understand disuse muscle atrophy, via magnetic resonance imaging, we
      sequentially measured muscle cross-sectional area along the entire length of all
      individual muscles from the hip to ankle in nine male subjects participating in
      60-day head-down tilt bed rest (2nd Berlin BedRest Study; BBR2-2). We
      hypothesized that individual muscles would not atrophy uniformly along their
      length such that different regions of an individual muscle would atrophy to
      different extents. This hypothesis was confirmed for the adductor magnus, vasti,
      lateral hamstrings, medial hamstrings, rectus femoris, medial gastrocnemius,
      lateral gastrocnemius, tibialis posterior, flexor hallucis longus, flexor
      digitorum longus, peroneals, and tibialis anterior muscles (P <= 0.004). In
      contrast, the hypothesis was not confirmed in the soleus, adductor brevis,
      gracilis, pectineus, and extensor digitorum longus muscles (P >= 0.20). The
      extent of atrophy only weakly correlated (r = -0.30, P < 0.001) with the location
      of greatest cross-sectional area. The rate of atrophy during bed rest also
      differed between muscles (P < 0.0001) and between some synergists. Most muscles
      recovered to their baseline size between 14 and 90 days after bed rest, but
      flexor hallucis longus, flexor digitorum longus, and lateral gastrocnemius
      required longer than 90 days before recovery occurred. On the basis of findings
      of differential atrophy between muscles and evidence in the literature, we
      interpret our findings of intramuscular atrophy to reflect differential disuse of
      functionally different muscle regions. The current work represents the first
      lower-limb wide survey of intramuscular differences in disuse atrophy. We
      conclude that intramuscular differential atrophy occurs in most, but not all, of
      the muscles of the lower limb during prolonged bed rest.

PMID- 22984242
TI  - Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus
      regulates sympathetic nerve activity responses to L-glutamate.
AB  - The hypothalamic paraventricular nucleus (PVN) is important for maintenance of
      sympathetic nerve activity (SNA) and cardiovascular function. PVN-mediated
      increases of SNA often involve the excitatory amino acid L-glutamate (L-glu),
      whose actions can be positively and negatively modulated by a variety of factors,
      including reactive oxygen species. Here, we determined modulatory effects of the
      highly diffusible reactive oxygen species hydrogen peroxide (H(2)O(2)) on
      responses to PVN L-glu. Renal SNA (RSNA), arterial blood pressure, and heart rate
      were recorded in anesthetized rats. L-Glu (0.2 nmol in 100 nl) microinjected
      unilaterally into PVN increased RSNA (P < 0.05), without affecting mean arterial
      blood pressure or heart rate. Effects of endogenously generated H(2)O(2) were
      determined by comparing responses to PVN L-glu before and after PVN injection of
      the catalase inhibitor 3-amino-1,2,4-triazole (ATZ; 100 nmol/200 nl, n = 5). ATZ
      alone was without effect on recorded variables, but attenuated the increase of
      RSNA elicited by PVN L-glu (P < 0.05). PVN injection of exogenous H(2)O(2) (5
      nmol in 100 nl, n = 4) and vehicle (artificial cerebrospinal fluid) were without
      affect, but H(2)O(2), like ATZ, attenuated the increase of RSNA to PVN L-glu (P <
      0.05). Tonic effects of endogenous H(2)O(2) were determined by PVN injection of
      polyethylene glycol-catalase (1.0 IU in 200 nl, n = 5). Whereas polyethylene
      glycol-catalase alone was without effect, increases of RSNA to subsequent PVN
      injection of L-glu were increased (P < 0.05). From these data, we conclude that
      PVN H(2)O(2) tonically, but submaximally, suppresses RSNA responses to L-glu,
      supporting the idea that a change of H(2)O(2) availability within PVN could
      influence SNA regulation under physiological and/or disease conditions.

PMID- 22984244
TI  - Shear elastic modulus can be used to estimate an index of individual muscle force
      during a submaximal isometric fatiguing contraction.
AB  - The present study was designed to determine whether fatigue alters the ability to
      estimate an index of individual muscle force from shear elastic modulus
      measurements (experiment I), and to test the ability of this technique to
      highlight changes in load sharing within a redundant muscle group during an
      isometric fatiguing task (experiment II). Twelve subjects participated in
      experiment I, which consisted of smooth linear torque ramps from 0 to 80% of
      maximal voluntary contraction (MVC) performed before and after an isometric
      fatigue protocol, beginning at 40% of MVC and stopped when the force production
      dropped below 30% of MVC. Although the relationships between modulus and torque
      were very similar for pre- and postfatigue [root mean square deviation
      (RMS(deviation)) = 3.7 +/- 2.6% of MVC], the relationships between
      electromyography activity level and torque were greatly altered by fatigue
      (RMS(deviation) = 10.3 +/- 2.6% of MVC). During the fatiguing contraction, shear
      elastic modulus provided a significantly lower RMS(deviation) between measured
      torque and estimated torque than electromyography activity level (5.7 +/- 0.9 vs.
      15.3 +/- 3.8% of MVC). Experiment II performed with eight participants consisted
      of an isometric knee extension at 25% of MVC sustained until exhaustion. Opposite
      changes in shear elastic modulus were observed between synergists (vastus
      medialis, vastus lateralis, and rectus femoris) of some participants, reflecting
      changes in load sharing. In conclusion, despite the fact that we did not directly
      estimate muscle force (in Newtons), this is the first demonstration of an
      experimental technique to accurately quantify relative changes in force in an
      individual human muscle during a fatiguing contraction.

PMID- 22984246
TI  - Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance
      arteries in mice.
AB  - Cardiovascular adaptations to microgravity undermine the physiological capacity
      to respond to orthostatic challenges upon return to terrestrial gravity. The
      purpose of the present study was to investigate the influence of spaceflight on
      vasoconstrictor and myogenic contractile properties of mouse gastrocnemius muscle
      resistance arteries. We hypothesized that vasoconstrictor responses acting
      through adrenergic receptors [norepinephrine (NE)], voltage-gated Ca(2+) channels
      (KCl), and stretch-activated (myogenic) mechanisms would be diminished following
      spaceflight. Feed arteries were isolated from gastrocnemius muscles, cannulated
      on glass micropipettes, and physiologically pressurized for in vitro
      experimentation. Vasoconstrictor responses to intraluminal pressure changes (0
      140 cmH(2)O), KCl (10-100 mM), and NE (10(-9)-10(-4) M) were measured in
      spaceflown (SF; n = 11) and ground control (GC; n = 11) female C57BL/6 mice.
      Spaceflight reduced vasoconstrictor responses to KCl and NE; myogenic
      vasoconstriction was unaffected. The diminished vasoconstrictor responses were
      associated with lower ryanodine receptor-2 (RyR-2) and ryanodine receptor-3 (RyR
      3) mRNA expression, with no difference in sarcoplasmic/endoplasmic Ca(2+) ATPase
      2 mRNA expression. Vessel wall thickness and maximal intraluminal diameter were
      unaffected by spaceflight. The data indicate a deficit in intracellular calcium
      release via RyR-2 and RyR-3 in smooth muscle cells as the mechanism of reduced
      contractile activity in skeletal muscle after spaceflight. Furthermore, the
      results suggest that impaired end-organ vasoconstrictor responsiveness of
      skeletal muscle resistance arteries contributes to lower peripheral vascular
      resistance and less tolerance of orthostatic stress in humans after spaceflight.

PMID- 22984245
TI  - The brain renin-angiotensin system and cardiovascular responses to stress:
      insights from transgenic rats with low brain angiotensinogen.
AB  - The renin-angiotensin system (RAS) has been identified as an attractive target
      for the treatment of stress-induced cardiovascular disorders. The effects of
      angiotensin (ANG) peptides during stress responses likely result from an
      integration of actions by circulating peptides and brain peptides derived from
      neuronal and glial sources. The present review focuses on the contribution of
      endogenous brain ANG peptides to pathways involved in cardiovascular responses to
      stressors. During a variety of forms of stress, neuronal pathways in forebrain
      areas containing ANG II or ANG-(1-7) are activated to stimulate descending
      angiotensinergic pathways that increase sympathetic outflow to increase blood
      pressure. We provide evidence that glia-derived ANG peptides influence brain
      AT(1) receptors. This appears to result in modulation of the responsiveness of
      the neuronal pathways activated during stressors that elevate circulating ANG
      peptides to activate brain pathways involving descending hypothalamic
      projections. It is well established that increased cardiovascular reactivity to
      stress is a significant predictor of hypertension and other cardiovascular
      diseases. This review highlights the importance of understanding the impact of
      RAS components from the circulation, neurons, and glia on the integration of
      cardiovascular responses to stressors.

PMID- 22984247
TI  - Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent
      adaptations in myofiber function in young and older men.
AB  - To examine potential age-specific adaptations in skeletal muscle size and
      myofiber contractile physiology in response to aerobic exercise, seven young (YM;
      20 +/- 1 yr) and six older men (OM; 74 +/- 3 yr) performed 12 wk of cycle
      ergometer training. Muscle biopsies were obtained from the vastus lateralis to
      determine size and contractile properties of isolated slow [myosin heavy chain
      (MHC) I] and fast (MHC IIa) myofibers, MHC composition, and muscle protein
      concentration. Aerobic capacity was higher (P < 0.05) after training in both YM
      (16 +/- 2%) and OM (13 +/- 3%). Quadriceps muscle volume, determined via MRI, was
      5 +/- 1 and 6 +/- 1% greater (P < 0.05) after training for YM and OM,
      respectively, which was associated with an increase in MHC I myofiber cross
      sectional area (CSA), independent of age. MHC I peak power was higher (P < 0.05)
      after training for both YM and OM, while MHC IIa peak power was increased (P <
      0.05) with training in OM only. MHC I and MHC IIa myofiber peak and normalized
      (peak force/CSA) force were preserved with training in OM, while MHC I peak
      force/CSA and MHC IIa peak force were lower (P < 0.05) after training in YM. The
      age-dependent adaptations in myofiber function were not due to changes in protein
      content, as total muscle protein and myofibrillar protein concentration were
      unchanged (P > 0.05) with training. Training reduced (P < 0.05) the proportion of
      MHC IIx isoform, independent of age, whereas no other changes in MHC composition
      were observed. These data suggest relative improvements in muscle size and
      aerobic capacity are similar between YM and OM, while adaptations in myofiber
      contractile function showed a general improvement in OM. Training-related
      increases in MHC I and MHC IIa peak power reveal that skeletal muscle of OM is
      responsive to aerobic exercise training and further support the use of aerobic
      exercise for improving cardiovascular and skeletal muscle health in older
      individuals.

PMID- 22984248
TI  - Positive end-expiratory pressure oscillation facilitates brain vascular
      reactivity monitoring.
AB  - The pressure reactivity index (PRx) identifies optimal cerebral perfusion
      pressure after traumatic brain injury. We describe a method to improve PRx
      precision by induced variations in arterial blood pressure (ABP) using positive
      end-expiratory pressure (PEEP) modulation (iPRx). Neonatal swine (n = 10) were
      ventilated with static PEEP and then with PEEP oscillated between 5 and 10
      cmH(2)O at a frequency of 1/min. PRx was recorded as a moving correlation
      coefficient between ABP and intracranial pressure (ICP) from spontaneous ABP
      activity (0.05-0.003 Hz) during static PEEP. iPRx was similarly recorded with
      PEEP oscillation-induced ABP waves. The lower limit of autoregulation (LLA) was
      delineated with continuous cortical laser Doppler flux monitoring. PEEP
      oscillation increased autoregulation-monitoring precision. The ratios of median
      absolute deviations to range of possible values for the PRx and iPRx were 9.5%
      (8.3-13.7%) and 6.2% (4.2-8.7%), respectively (P = 0.006; median, interquartile
      range). The phase-angle difference between ABP and ICP above LLA was 161 degrees 
      (150 degrees -166 degrees ) and below LLA, -31 degrees  (-42 degrees  to 12
      degrees , P < 0.0001). iPRx above LLA was -0.42 (-0.67 to -0.29) and below LLA,
      0.32 (0.22-0.43, P = 0.0004). A positive iPRx was 97% specific and 91% sensitive
      for perfusion pressure below LLA. PEEP oscillation caused stable, low-frequency
      ABP oscillations that reduced noise in the PRx. Safe translation of these
      findings to clinical settings is expected to yield more accurate and rapid
      delineation of individualized optimal perfusion-pressure goals for patients.

PMID- 22984250
TI  - Cardiovascular responses to lower body negative pressure before and after 4 h of
      head-down bed rest and seated control in men and women.
AB  - Cardiovascular deconditioning after a 4-h head-down bed rest (HDBR) might be a
      consequence of the time of day relative to pre-HDBR testing, or simply 4 h of
      confinement and inactivity rather than the posture change. Ten men and 11 women
      were studied during lower body negative pressure (LBNP) before and after 4-h HDBR
      and 4-h seated posture (SEAT) as a control for time of day and physical
      inactivity effects to test the hypotheses that cardiovascular deconditioning was
      a consequence of the HDBR posture, and that women would have a greater
      deconditioning response. Following HDBR, men and women had lower blood volume,
      higher heart rate with a greater increase during LBNP, a greater decrease of
      stroke volume during LBNP, lower central venous pressure, smaller inferior vena
      cava diameter, higher portal vein resistance index with a greater increase during
      LBNP, but lower forearm vascular resistance, lower norepinephrine, and lower
      renin. Women had lower vasopressin and men had higher vasopressin after HDBR, and
      women had lower pelvic impedance and men higher pelvic impedance. Following SEAT,
      brachial vascular resistance was reduced, thoracic impedance was elevated, the
      reduction of central venous pressure during LBNP was changed, women had higher
      angiotensin II whereas men had lower levels, and pelvic impedance increased in
      women and decreased in men. Cardiovascular deconditioning was greater after 4-h
      HDBR than after SEAT. Women and men had similar responses for most cardiovascular
      variables in the present study that tested the responses to LBNP after short
      duration HDBR compared with a control condition.

PMID- 22984249
TI  - Role of TNFR1 in the innate airway hyperresponsiveness of obese mice.
AB  - The purpose of this study was to examine the role of tumor necrosis factor
      receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese
      mice. Airway responsiveness to intravenous methacholine was measured using the
      forced oscillation technique in obese Cpe(fat) mice that were either sufficient
      or genetically deficient in TNFR1 (Cpe(fat) and Cpe(fat)/TNFR1(-/-) mice) and in
      lean mice that were either sufficient or genetically deficient in TNFR1 [wild
      type (WT) and TNFR1(-/-) mice]. Compared with lean WT mice, Cpe(fat) mice
      exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in
      Cpe(fat)/TNFR1(-/-) than in Cpe(fat) mice. Compared with WT mice, Cpe(fat) mice
      had increases in bronchoalveolar lavage fluid concentrations of several
      inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These
      factors were also significantly elevated in Cpe(fat)/TNFR1(-/-) vs. TNFR1(-/-)
      mice. Additional moieties including IL-13 were also elevated in Cpe(fat)/TNFR1(-/
      ) vs. TNFR1(-/-) mice but not in Cpe(fat) vs. WT mice. IL-17A mRNA expression was
      greater in Cpe(fat)/TNFR1(-/-) vs. Cpe(fat) mice and in TNFR1(-/-) vs. WT mice.
      Analysis of serum indicated that obesity resulted in systemic as well as
      pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic
      inflammation. Our results indicate that TNFR1 is protective against the airway
      hyperresponsiveness associated with obesity and suggest that effects on pulmonary
      inflammation may be contributing to this protection.

PMID- 22984251
TI  - Contributions of ocular vestibular evoked myogenic potentials and the
      electrooculogram to periocular potentials produced by whole-body vibration.
AB  - In this paper we report the results of an experiment to investigate the emergence
      of ocular vestibular evoked myogenic potentials (OVEMPs) during the linear
      vestibular ocular reflex (LVOR) evoked by whole-body vibration (WBV). OVEMP and
      electrooculogram (EOG) montages were employed to record periocular potentials
      (POPs) from six subjects during WBV in the nasooccipital (NO) axis over a range
      of frequencies from 0.5 to 64 Hz with approximately constant peak head
      acceleration of 1.0 ms(-2) (i.e., 0.1 g). Measurements were made in two context
      conditions: a fixation context to examine the effect of gaze eccentricity (0 vs.
      20 degrees ), and a visual context, where a target was either head-fixed or earth
      fixed. The principal results are that from 0.5 to 2 Hz POP magnitude in the earth
      fixed condition is related to head displacement, so with constant acceleration at
      all frequencies it reduces with increasing frequency, but at frequencies greater
      than 2 Hz both POP magnitude and POP gain, defined as the ratio of POP magnitude
      at 20 and 0 degrees , increase with increasing frequency. By exhibiting this high
      pass characteristic, a property shared with the LVOR, the results are consistent
      with the hypothesis that the OVEMP, as commonly employed in the clinical setting,
      is a high-frequency manifestation of the LVOR. However, we also observed low
      frequency acceleration following POPs in head-fixed conditions, consistent with a
      low-frequency OVEMP, and found evidence of a high-frequency visual context
      effect, which is also consistent with the OVEMP being a manifestation of the
      LVOR.

PMID- 22984252
TI  - Simvastatin attenuates sympathetic hyperinnervation to prevent atrial
      fibrillation during the postmyocardial infarction remodeling process.
AB  - Statin, as a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, has been shown
      to prevent atrial fibrillation (AF) due to its anti-inflammatory and antioxidant
      effects. However, it is still not known whether statin can improve autonomic
      remodeling to prevent AF. In the present study, using an in vivo rat myocardial
      infarction (MI) model, we aimed to test whether simvastatin can attenuate nerve
      sprouting and sympathetic hyperinnervation to prevent AF during the post-MI
      remodeling process. Our data demonstrate that simvastatin, delivered 3 days after
      MI for 4 wk, can result in significant decreases in plasma levels of both TNF
      alpha (239 +/- 23 pg/ml) and IL-1beta (123 +/- 11 pg/ml) compared with MI rats
      without therapy (TNF-alpha, 728 +/- 57 pg/ml; IL-1beta, 213 +/- 21 pg/ml; P <
      0.05), which, however, were still higher than sham-operated rats (TNF-alpha, 194
      +/- 20 pg/ml; IL-1beta, 75 +/- 8 pg/ml; P < 0.05). The similar pattern of changes
      in inflammation responses was also observed in TNF-alpha and IL-1beta protein
      expression in the left atrium free wall. The suppressed inflammation responses
      were associated with reduced superoxide and malondialdehyde generation in the
      atrium. These changes account for decreases in neural growth factor expression at
      levels of both mRNA (1.2 +/- 0.09 AU vs. MI group, 1.78 +/- 0.16 AU) and protein
      (1.57 +/- 0.17 AU vs. MI group, 2.24 +/- 0.19 AU; P < 0.05), thus resulting in
      reduced nerve sprouting and sympathetic hyperinnervation. Accordingly, the rate
      adaptation of the atrial effective refractory period also recovered, leading to
      the decreased inducibility of AF. These data suggest that simvastatin
      administration after MI can prevent AF through reduced sympathetic
      hyperinnervation.

PMID- 22984253
TI  - Maximal strength training and increased work efficiency: contribution from the
      trained muscle bed.
AB  - Maximal strength training (MST) reduces pulmonary oxygen uptake (Vo(2)) at a
      given submaximal exercise work rate (i.e., efficiency). However, whether the
      increase in efficiency originates in the trained skeletal muscle, and therefore
      the impact of this adaptation on muscle blood flow and arterial-venous oxygen
      difference (a-vO(2diff)), is unknown. Thus five trained subjects partook in an 8
      wk MST intervention consisting of half-squats with an emphasis on the rate of
      force development during the concentric phase of the movement. Pre- and
      posttraining measurements of pulmonary Vo(2) (indirect calorimetry), single-leg
      blood flow (thermodilution), and single-leg a-vO(2diff) (blood gases) were
      performed, to allow the assessment of skeletal muscle Vo(2) during submaximal
      cycling [237 +/- 23 W; ~60% of their peak pulmonary Vo(2) (Vo(2peak))]. Pulmonary
      Vo(2peak) (~4.05 l/min) and peak work rate (~355 W), assessed during a graded
      exercise test, were unaffected by MST. As expected, following MST there was a
      significant reduction in pulmonary Vo(2) during steady-state submaximal cycling
      (~237 W: 3.2 +/- 0.1 to 2.9 +/- 0.1 l/min). This was accompanied by a significant
      reduction in single-leg Vo(2) (1,101 +/- 105 to 935 +/- 93 ml/min) and single-leg
      blood flow (6,670 +/- 700 to 5,649 +/- 641 ml/min), but no change in single-leg a
      vO(2diff) (16.7 +/- 0.8 to 16.8 +/-0.4 ml/dl). These data confirm an MST-induced
      reduction in pulmonary Vo(2) during submaximal exercise and identify that this
      change in efficiency originates solely in skeletal muscle, reducing muscle blood
      flow, but not altering muscle a-vO(2diff).

PMID- 22984254
TI  - Differential control of the rate of 5'-end-dependent mRNA degradation in
      Escherichia coli.
AB  - Many Escherichia coli mRNAs are degraded by a 5'-end-dependent mechanism in which
      RppH-catalyzed conversion of the 5'-terminal triphosphate to a monophosphate
      triggers rapid endonucleolytic cleavage by RNase E. However, little is understood
      about what governs the decay rates of these transcripts. We investigated the
      decay of three such messages--rpsT P1, yfcZ, and ydfG--to characterize the rate
      determining step in their degradation. The steady-state ratio of
      monophosphorylated to triphosphorylated rpsT P1 and yfcZ mRNA indicates that
      their decay rate is limited by cleavage of the monophosphorylated intermediate,
      making RNase E critical for their rapid turnover. Conversely, the decay rate of
      ydfG is limited by generation of the monophosphorylated intermediate; therefore,
      either RNase E or its less abundant paralog RNase G is sufficient for rapid ydfG
      degradation. Although all three transcripts are stabilized when RppH is absent,
      overproducing RppH does not accelerate their decay, nor does RppH overproduction
      appear to influence the longevity of most other messages that it targets. The
      failure of excess RppH to hasten rpsT P1 and yfcZ degradation despite increasing
      the percentage of each that is monophosphorylated is consistent with the
      observation that pyrophosphate removal is not the rate-limiting step in their
      decay. In contrast, neither the ydfG decay rate nor the fraction of ydfG
      transcripts that are monophosphorylated increases when the cellular concentration
      of RppH is raised, suggesting that, for some RppH targets, the rate of formation
      of the monophosphorylated intermediate is limited by an ancillary factor or by a
      step that precedes pyrophosphate removal.

PMID- 22984255
TI  - Analysis of the regulated transcriptome of Neisseria meningitidis in human blood
      using a tiling array.
AB  - Neisseria meningitidis is the major cause of septicemia and meningococcal
      meningitis. During the course of infection, the bacterium must adapt to different
      host environments as a crucial factor for survival and dissemination; in
      particular, one of the crucial factors in N. meningitidis pathogenesis is the
      ability to grow and survive in human blood. We recently showed that N.
      meningitidis alters the expression of 30% of the open reading frames (ORFs) of
      the genome during incubation in human whole blood and suggested the presence of
      fine regulation at the gene expression level in order to control this step of
      pathogenesis. In this work, we used a customized tiling oligonucleotide
      microarray to define the changes in the whole transcriptional profile of N.
      meningitidis in a time course experiment of ex vivo bacteremia by incubating
      bacteria in human whole blood and then recovering RNA at different time points.
      The application of a newly developed bioinformatic tool to the tiling array data
      set allowed the identification of new transcripts--small intergenic RNAs, cis
      encoded antisense RNAs, mRNAs with extended 5' and 3' untranslated regions
      (UTRs), and operons--differentially expressed in human blood. Here, we report a
      panel of expressed small RNAs, some of which can potentially regulate genes
      involved in bacterial metabolism, and we show, for the first time in N.
      meningitidis, extensive antisense transcription activity. This analysis suggests
      the presence of a circuit of regulatory RNA elements used by N. meningitidis to
      adapt to proliferate in human blood that is worthy of further investigation.

PMID- 22984256
TI  - The C-terminal domain of the virulence factor MgtC is a divergent ACT domain.
AB  - MgtC is a virulence factor of unknown function important for survival inside
      macrophages in several intracellular bacterial pathogens, including Mycobacterium
      tuberculosis. It is also involved in adaptation to Mg(2+) deprivation, but
      previous work suggested that MgtC is not a Mg(2+) transporter. In this study, we
      demonstrated that the amount of the M. tuberculosis MgtC protein is not
      significantly increased by Mg(2+) deprivation. Members of the MgtC protein family
      share a conserved membrane N-terminal domain and a more divergent cytoplasmic C
      terminal domain. To get insights into MgtC functional and structural
      organization, we have determined the nuclear magnetic resonance (NMR) structure
      of the C-terminal domain of M. tuberculosis MgtC. This structure is not affected
      by the Mg(2+) concentration, indicating that it does not bind Mg(2+). The
      structure of the C-terminal domain forms a betaalphabetabetaalphabeta fold found
      in small molecule binding domains called ACT domains. However, the M.
      tuberculosis MgtC ACT domain differs from canonical ACT domains because it
      appears to lack the ability to dimerize and to bind small molecules. We have
      shown, using a bacterial two-hybrid system, that the M. tuberculosis MgtC protein
      can dimerize and that the C-terminal domain somehow facilitates this
      dimerization. Taken together, these results indicate that M. tuberculosis MgtC
      does not have an intrinsic function related to Mg(2+) uptake or binding but could
      act as a regulatory factor based on protein-protein interaction that could be
      facilitated by its ACT domain.

PMID- 22984257
TI  - Bacillus subtilis hlpB encodes a conserved stand-alone HNH nuclease-like protein
      that is essential for viability unless the hlpB deletion is accompanied by the
      deletion of genes encoding the AddAB DNA repair complex.
AB  - The HNH domain is found in many different proteins in all phylogenetic kingdoms
      and in many cases confers nuclease activity. We have found that the Bacillus
      subtilis hlpB (yisB) gene encodes a stand-alone HNH domain, homologs of which are
      present in several bacterial genomes. We show that the protein we term HlpB is
      essential for viability. The depletion of HlpB leads to growth arrest and to the
      generation of cells containing a single, decondensed nucleoid. This apparent
      condensation-segregation defect was cured by additional hlpB copies in trans.
      Purified HlpB showed cooperative binding to a variety of double-stranded and
      single-stranded DNA sequences, depending on the presence of zinc, nickel, or
      cobalt ions. Binding of HlpB was also influenced by pH and different metals,
      reminiscent of HNH domains. Lethality of the hlpB deletion was relieved in the
      absence of addA and of addAB, two genes encoding proteins forming a RecBCD-like
      end resection complex, but not of recJ, which is responsible for a second end
      resectioning avenue. Like AddA-green fluorescent protein (AddA-GFP), functional
      HlpB-YFP or HlpB-FlAsH fusions were present throughout the cytosol in growing B.
      subtilis cells. Upon induction of DNA damage, HlpB-FlAsH formed a single focus on
      the nucleoid in a subset of cells, many of which colocalized with the replication
      machinery. Our data suggest that HlpB plays a role in DNA repair by rescuing
      AddAB-mediated recombination intermediates in B. subtilis and possibly also in
      many other bacteria.

PMID- 22984258
TI  - Transposon mutagenesis identifies uropathogenic Escherichia coli biofilm factors.
AB  - Uropathogenic Escherichia coli (UPEC), which accounts for 85% of urinary tract
      infections (UTI), assembles biofilms in diverse environments, including the host.
      Besides forming biofilms on biotic surfaces and catheters, UPEC has evolved an
      intracellular pathogenic cascade that culminates in the formation of biofilm-like
      intracellular bacterial communities (IBCs) within bladder epithelial cells. Rapid
      bacterial replication during IBC formation augments a build-up in bacterial
      numbers and persistence within the host. Relatively little is known about factors
      mediating UPEC biofilm formation and how these overlap with IBC formation. To
      address this gap, we screened a UPEC transposon mutant library in three in vitro
      biofilm conditions: Luria broth (LB)-polyvinyl chloride (PVC), YESCA (yeast
      extract-Casamino Acids)-PVC, and YESCA-pellicle that are dependent on type 1 pili
      (LB) and curli (YESCA), respectively. Flagella are important in all three
      conditions. Mutants were identified that had biofilm defects in all three
      conditions but had no significant effects on the expression of type 1 pili,
      curli, or flagella. Thus, this approach uncovered a comprehensive inventory of
      novel effectors and regulators that are involved in UPEC biofilm formation under
      multiple conditions. A subset of these mutants was found to be dramatically
      attenuated and unable to form IBCs in a murine model of UTI. Collectively, this
      study expands our insights into UPEC multicellular behavior that may provide
      insights into IBC formation and virulence.

PMID- 22984259
TI  - Coupling of sigmaG activation to completion of engulfment during sporulation of
      Bacillus subtilis survives large perturbations to DNA translocation and
      replication.
AB  - Spore formation in Bacillus subtilis is characterized by activation of RNA
      polymerase sigma factors, including the late-expressed sigma(G). During spore
      formation an asymmetric division occurs, yielding the smaller prespore and the
      larger mother cell. At division, only 30% of the chromosome is in the prespore,
      and the rest is then translocated into the prespore. Following completion of
      engulfment of the prespore by the mother cell, sigma(G) is activated in the
      prespore. Here we tested the link between engulfment and sigma(G) activation by
      perturbing DNA translocation and replication, which are completed before
      engulfment. One approach was to have large DNA insertions in the chromosome; the
      second was to have an impaired DNA translocase; the third was to use a strain in
      which the site of termination of chromosome replication was relocated. Insertion
      of 2.3 Mb of Synechocystis DNA into the B. subtilis genome had the largest
      effect, delaying engulfment by at least 90 min. Chromosome translocation was also
      delayed and was completed shortly before the completion of engulfment. Despite
      the delay, sigma(G) became active only after the completion of engulfment. All
      results are consistent with a strong link between completion of engulfment and
      sigma(G) activation. They support a link between completion of chromosome
      translocation and completion of engulfment.

PMID- 22984260
TI  - Streptococcus pneumoniae uses glutathione to defend against oxidative stress and
      metal ion toxicity.
AB  - The thiol-containing tripeptide glutathione is an important cellular constituent
      of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase
      activity, glutathione is known to protect cells from many forms of physiological
      stress. This report represents the first investigation into the role of
      glutathione in the Gram-positive pathogen Streptococcus pneumoniae. We
      demonstrate that pneumococci import extracellular glutathione using the ABC
      transporter substrate binding protein GshT. Mutation of gshT and the gene
      encoding glutathione reductase (gor) increases pneumococcal sensitivity to the
      superoxide generating compound paraquat, illustrating the importance of
      glutathione utilization in pneumococcal oxidative stress resistance. In addition,
      the gshT and gor mutant strains are hypersensitive to challenge with the divalent
      metal ions copper, cadmium, and zinc. The importance of glutathione utilization
      in pneumococcal colonization and invasion of the host is demonstrated by the
      attenuated phenotype of the gshT mutant strain in a mouse model of infection.

PMID- 22984262
TI  - Sequence-verified two-allele transposon mutant library for Pseudomonas aeruginosa
      PAO1.
AB  - Mutant hunts using comprehensive sequence-defined libraries make it possible to
      identify virtually all of the nonessential functions required for different
      bacterial processes. However, the success of such screening depends on the
      accuracy of mutant identification in the mutant library used. To provide a high
      quality library for Pseudomonas aeruginosa PAO1, we created a sequence-verified
      collection of 9,437 transposon mutants that provides genome coverage and includes
      two mutants for most genes. Mutants were cherry-picked from a larger library,
      colony-purified, and resequenced both individually using Sanger sequencing and in
      a pool using Tn-seq. About 8% of the insertion assignments were corrected, and in
      the final library nearly 93% of the transposon locations were confirmed by at
      least one of the resequencing procedures. The extensive sequence verification and
      inclusion of more than one mutant for most genes should help minimize missed or
      erroneous genotype-phenotype assignments in studies using the new library.

PMID- 22984261
TI  - Novel high-molecular-weight, R-type bacteriocins of Clostridium difficile.
AB  - Clostridium difficile causes one of the leading nosocomial infections in
      developed countries, and therapeutic choices are limited. Some strains of C.
      difficile produce phage tail-like particles upon induction of the SOS response.
      These particles have bactericidal activity against other C. difficile strains and
      can therefore be classified as bacteriocins, similar to the R-type pyocins of
      Pseudomonas aeruginosa. These R-type bacteriocin particles, which have been
      purified from different strains, each have a different C. difficile-killing
      spectrum, with no one bacteriocin killing all C. difficile isolates tested. We
      have identified the genetic locus of these "diffocins" (open reading frames 1359
      to 1376) and have found them to be common among the species. The entire diffocin
      genetic locus of more than 20 kb was cloned and expressed in Bacillus subtilis,
      and this resulted in production of bactericidal particles. One of the interesting
      features of these particles is a very large structural protein of ~200 kDa, the
      product of gene 1374. This large protein determines the killing spectrum of the
      particles and is likely the receptor-binding protein. Diffocins may provide an
      alternate bactericidal agent to prevent or treat infections and to decolonize
      individuals who are asymptomatic carriers.

PMID- 22984263
TI  - Crystal structures of complexes of the branched-chain aminotransferase from
      Deinococcus radiodurans with alpha-ketoisocaproate and L-glutamate suggest the
      radiation resistance of this enzyme for catalysis.
AB  - Branched-chain aminotransferases (BCAT), which utilize pyridoxal 5'-phosphate
      (PLP) as a cofactor, reversibly catalyze the transfer of the alpha-amino groups
      of three of the most hydrophobic branched-chain amino acids (BCAA), leucine,
      isoleucine, and valine, to alpha-ketoglutarate to form the respective branched
      chain alpha-keto acids and glutamate. The BCAT from Deinococcus radiodurans
      (DrBCAT), an extremophile, was cloned and expressed in Escherichia coli for
      structure and functional studies. The crystal structures of the native DrBCAT
      with PLP and its complexes with L-glutamate and alpha-ketoisocaproate (KIC),
      respectively, have been determined. The DrBCAT monomer, comprising 358 amino
      acids, contains large and small domains connected with an interdomain loop. The
      cofactor PLP is located at the bottom of the active site pocket between two
      domains and near the dimer interface. The substrate (L-glutamate or KIC) is bound
      with key residues through interactions of the hydrogen bond and the salt bridge
      near PLP inside the active site pocket. Mutations of some interaction residues,
      such as Tyr71, Arg145, and Lys202, result in loss of the specific activity of the
      enzymes. In the interdomain loop, a dynamic loop (Gly173 to Gly179) clearly
      exhibits open and close conformations in structures of DrBCAT without and with
      substrates, respectively. DrBCAT shows the highest specific activity both in
      nature and under ionizing radiation, but with lower thermal stability above 60 
      degrees C, than either BCAT from Escherichia coli (eBCAT) or from Thermus
      thermophilus (HB8BCAT). The dimeric molecular packing and the distribution of
      cysteine residues at the active site and the molecular surface might explain the
      resistance to radiation but small thermal stability of DrBCAT.

PMID- 22984264
TI  - N-myristoylation and Ca2+ binding of calcineurin B homologous protein CHP3 are
      required to enhance Na+/H+ exchanger NHE1 half-life and activity at the plasma
      membrane.
AB  - Calcineurin B homologous proteins (CHP) are N-myristoylated, EF-hand Ca(2+)
      binding proteins that regulate multiple cellular processes, including
      intracellular pH homeostasis. Previous work has shown that the heart-enriched
      isoform, CHP3, regulates the plasmalemmal Na(+)/H(+) exchanger NHE1 isoform by
      enhancing its rate of oligosaccharide maturation and exocytosis as well as its
      half-life and transport activity at the cell surface (Zaun, H. C., Shrier, A.,
      and Orlowski, J. (2008) J. Biol. Chem. 283, 12456-12467). However, the molecular
      basis for this effect is not well understood. In this report, we investigated
      whether the N-myristoylation and Ca(2+)-binding domains of CHP3 are important
      elements for regulating NHE1. Mutation of residues essential for either N
      myristoylation (G2A) or calcium binding (D123A) did not prevent the interaction
      of CHP3 with NHE1, although the D123A mutant no longer showed elevated binding to
      NHE1 in the presence of Ca(2+) when assessed using in vitro binding assays.
      Disruption of either site also did not impair the ability of CHP3 to stimulate
      the biosynthetic processing and trafficking of NHE1 to the plasma membrane nor
      did it affect the H(+) sensitivity of the exchanger. However, they did
      significantly reduce the cell surface half-life and near maximal transport
      velocity of NHE1 to a similar extent. Simultaneous mutation of both sites
      (G2A/D123A) gave results identical to the individual substitutions. This finding
      suggests that both domains in CHP3 are interdependent and may function
      cooperatively as a Ca(2+)-myristoyl switch mechanism to selectively stabilize the
      NHE1.CHP3 complex at the cell surface in a conformation that promotes optimal
      transport activity.

PMID- 22984265
TI  - 14-3-3epsilon and 14-3-3sigma inhibit Toll-like receptor (TLR)-mediated
      proinflammatory cytokine induction.
AB  - Toll-like receptors (TLRs) are a group of pattern recognition receptors that play
      a crucial role in the induction of the innate immune response against bacterial
      and viral infections. TLR3 has emerged as a key sensor of viral double-stranded
      RNA. Thus, a clearer understanding of the biological processes that modulate TLR3
      signaling is essential. Limited studies have applied proteomics toward
      understanding the dynamics of TLR signaling. Herein, a proteomics approach
      identified 14-3-3epsilon and 14-3-3sigma proteins as new members of the TLR
      signaling complex. Toward the functional characterization of 14-3-3epsilon and 14
      3-3sigma in TLR signaling, we have shown that both of these proteins impair TLR2,
      TLR3, TLR4, TLR7/8, and TLR9 ligand-induced IL-6, TNFalpha, and IFN-beta
      production. We also show that 14-3-3epsilon and 14-3-3sigma impair TLR2-, TLR3-,
      TLR4-, TLR7/8-, and TLR9-mediated NF-kappaB and IFN-beta reporter gene activity.
      Interestingly, although the 14-3-3 proteins inhibit poly(I:C)-mediated RANTES
      production, 14-3-3 proteins augment Pam(3)CSK(4), LPS, R848, and CpG-mediated
      production of RANTES (regulated on activation normal T cell expressed and
      secreted) in a Mal (MyD88 adaptor-like)/MyD88-dependent manner. 14-3-3epsilon and
      14-3-3sigma also bind to the TLR adaptors and to both TRAF3 and TRAF6. Our study
      conclusively shows that 14-3-3epsilon and 14-3-3sigma play a major regulatory
      role in balancing the host inflammatory response to viral and bacterial
      infections through modulation of the TLR signaling pathway. Thus, manipulation of
      14-3-3 proteins may represent novel therapeutic targets for inflammatory
      conditions and infections.

PMID- 22984267
TI  - Proteolytic activation of the essential parasitophorous vacuole cysteine protease
      SERA6 accompanies malaria parasite egress from its host erythrocyte.
AB  - The malaria parasite replicates within an intraerythrocytic parasitophorous
      vacuole (PV). The PV and host cell membranes eventually rupture, releasing
      merozoites in a process called egress. Certain inhibitors of serine and cysteine
      proteases block egress, indicating a crucial role for proteases. The Plasmodium
      falciparum genome encodes nine serine-repeat antigens (SERAs), each of which
      contains a central domain homologous to the papain-like (clan CA, family C1)
      protease family. SERA5 and SERA6 are indispensable in blood-stage parasites, but
      the function of neither is known. Here we show that SERA6 localizes to the PV
      where it is precisely cleaved just prior to egress by an essential serine
      protease called PfSUB1. Mutations that replace the predicted catalytic Cys of
      SERA6, or that block SERA6 processing by PfSUB1, could not be stably introduced
      into the parasite genomic sera6 locus, indicating that SERA6 is an essential
      enzyme and that processing is important for its function. We demonstrate that
      cleavage of SERA6 by PfSUB1 converts it to an active cysteine protease. Our
      observations reveal a proteolytic activation step in the malarial PV that may be
      required for release of the parasite from its host erythrocyte.

PMID- 22984266
TI  - Processing and topology of the yeast mitochondrial phosphatidylserine
      decarboxylase 1.
AB  - The inner mitochondrial membrane plays a crucial role in cellular lipid
      homeostasis through biosynthesis of the non-bilayer-forming lipids
      phosphatidylethanolamine and cardiolipin. In the yeast Saccharomyces cerevisiae,
      the majority of cellular phosphatidylethanolamine is synthesized by the
      mitochondrial phosphatidylserine decarboxylase 1 (Psd1). The biogenesis of Psd1
      involves several processing steps. It was speculated that the Psd1 precursor is
      sorted into the inner membrane and is subsequently released into the
      intermembrane space by proteolytic removal of a hydrophobic sorting signal.
      However, components involved in the maturation of the Psd1 precursor have not
      been identified. We show that processing of Psd1 involves the action of the
      mitochondrial processing peptidase and Oct1 and an autocatalytic cleavage at a
      highly conserved LGST motif yielding the alpha- and beta-subunit of the enzyme.
      The Psd1 beta-subunit (Psd1beta) forms the membrane anchor, which binds the
      intermembrane space-localized alpha-subunit (Psd1alpha). Deletion of a
      transmembrane segment in the beta-subunit results in mislocalization of Psd1 and
      reduced enzymatic activity. Surprisingly, autocatalytic cleavage does not depend
      on proper localization to the inner mitochondrial membrane. In summary, membrane
      integration of Psd1 is crucial for its functionality and for maintenance of
      mitochondrial lipid homeostasis.

PMID- 22984268
TI  - ZAP-70+ B cell subset influences response to B cell depletion therapy and early
      repopulation in rheumatoid arthritis.
AB  - OBJECTIVE: To define the role of ZAP-70+ B cells (CD19+/ZAP-70+) as a biomarker
      of response to B cell depletion therapy (BCDT), their relationship with clinical
      outcome, and their behavior during repopulation of peripheral blood in patients
      with rheumatoid arthritis (RA). METHODS: Thirty-one patients with RA underwent
      BCDT and were followed for 12 months. Disease activity was assessed with the
      European League Against Rheumatism (EULAR) criteria. Cytofluorimetric analysis of
      peripheral blood B cell subsets at baseline and at 6- and 12-month intervals
      after BCDT was performed using surface markers (CD45, CD3, CD56, CD19, IgD, CD38,
      CD27) and intracellular ZAP-70. RESULTS: A moderate/good EULAR response was
      achieved in 66.6% of the RA cohort. The baseline percentage of CD19+/ZAP-70+
      cells was lower in good responder patients (1.8% +/- 1.7%) compared to poor
      responders (5.6% +/- 4.9%; p = 0.02). A decrease of plasmablasts (IgD-CD27+CD38+)
      and pre-switch memory (IgD+CD27+) B cells occurred after BCDT. Recovery of B
      cells in peripheral blood after the first course of BCDT was characterized by the
      reappearance of B cell subtypes that showed a naive, activated phenotype, coupled
      with a decrease in memory cells. B cells carrying intracytoplasmic ZAP-70
      increased significantly from the baseline value of 4.4% +/- 4.5% to 12.4% +/-
      9.2% (p = 0.001) at the 6-month and to 9.4% +/- 6.4% (p = 0.002) at the 12-month
      followup. CONCLUSION: Baseline percentage of CD19+/ZAP-70+ cells is associated
      with the clinical outcome after BCDT in patients with RA. Depletion of
      plasmablasts and pre-switch memory B cells and increase of CD19+/ZAP-70+ cells
      are features of the recovery of the B cell pool after BCDT.

PMID- 22984269
TI  - Efficacy and safety of rituximab treatment in patients with antineutrophil
      cytoplasmic antibody-associated vasculitides: results from a German registry
      (GRAID).
AB  - OBJECTIVE: Rituximab (RTX) therapy is a treatment option in patients with
      refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV). We investigated the tolerability and clinical efficacy of RTX in a cohort
      of patients with refractory AAV. METHODS: Clinical and safety data of patients
      with AAV treated with RTX were retrospectively assessed from the data of a German
      national registry. RESULTS: In total, 58 patients were included in this analysis
      (50/58 with granulomatosis with polyangiitis; 8/58 with microscopic polyangiitis
      who received at least 1 cycle, 17 patients who received 2 cycles, and 3 patients
      who received 3 cycles of RTX). Response was classified as complete and partial in
      22 (40%) and in 29 cases (52.7%), respectively. Four patients (7.3%) were
      classified as nonresponders. CONCLUSION: RTX was well tolerated with good
      clinical efficacy in patients with refractory AAV.

PMID- 22984270
TI  - Comparison of the 2010 American College of Rheumatology/European League Against
      Rheumatism and the 1987 American Rheumatism Association classification criteria
      for rheumatoid arthritis in an early arthritis cohort in New Zealand.
AB  - OBJECTIVE: To compare the performance of the 2010 American College of
      Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria with the
      1987 American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA)
      in an early arthritis cohort. METHODS: The study included 79 patients with early
      arthritis (symptoms < 12 months) and a minimum of 1 year of followup between
      January 2004 and August 2010. Case notes were reviewed to determine which
      criteria were fulfilled at initial, 3-month, 1-year, and 2-year visits.
      Requirements for disease-modifying antirheumatic drug (DMARD) therapy and
      presence of joint erosions were compared at 2 years. RESULTS: At the initial
      visit, twice as many patients fulfilled the 2010 criteria (67%) compared with the
      1987 criteria (34%; p < 0.001). Forty-four percent of patients who fulfilled only
      the 2010 criteria at the initial visit went on to fulfill both 1987 and 2010
      criteria at 3 months (p < 0.001). Eight patients did not meet the 1987 RA
      criteria solely because of short symptom duration. All 17/79 patients who
      developed joint erosions went on to eventually fulfill both criteria. Of those
      patients who fulfilled only the 2010 criteria at baseline, 25/27 (93%) ultimately
      received DMARD therapy compared with 24/26 (92%) of those fulfilling both 1987
      and 2010 criteria. CONCLUSION: The 2010 ACR/EULAR RA criteria allowed earlier RA
      classification compared to the 1987 ARA criteria, although both criteria were
      equivalent in predicting joint erosions and subsequent need for DMARD (Australian
      New Zealand Clinical Trials Registry ANZCTR 12608000292370).

PMID- 22984271
TI  - Giant cell arteritis with or without aortitis at diagnosis. A retrospective study
      of 22 patients with longterm followup.
AB  - OBJECTIVE: Studies have shown that aortitis may be present in half the patients
      with recent-onset giant cell arteritis (GCA). We assessed whether aortitis at
      diagnosis affects longterm outcome in patients with GCA. METHODS: We
      retrospectively analyzed the longterm outcome of a prospective cohort of 22
      patients with biopsy-proven GCA who all had aortic computed tomography (CT)
      evaluation at the time of diagnosis of GCA between May 1998 and November 1999.
      Longterm outcome, especially vascular events such as aortic aneurysm, mortality,
      relapses of GCA, and requirement for steroids, was assessed in 2011 by chart
      review and patient/physician interviews. RESULTS: At disease onset, 10/22
      patients had aortitis on CT scan. Patients with and without aortitis had similar
      baseline characteristics, including cardiovascular risk profile. At the time of
      the study, 12/22 (57%) patients had died. Vascular causes of death were more
      frequent in patients with aortitis (5/7 vs 0/5; p = 0.02). A higher number of
      vascular events was noted in patients with aortitis (mean events per patient 1.33
      vs 0.25; p = 0.009). Stroke was more frequent in patients with aortitis. These
      patients seemed to exhibit a more chronic or relapsing disease course, and they
      were less likely to completely discontinue steroid therapy (p = 0.009, log-rank
      test). CONCLUSION: Our study suggests for the first time that inflammatory aortic
      involvement present at onset of GCA could predict a more chronic/relapsing course
      of GCA, with higher steroid requirements and an increased risk for vascular
      events in the long term.

PMID- 22984272
TI  - Infliximab is associated with improvement in arterial stiffness in patients with
      early rheumatoid arthritis -- a randomized trial.
AB  - OBJECTIVE: To determine the efficacy of methotrexate (MTX) with infliximab (IFX)
      compared with MTX alone in the prevention of atherosclerosis and arterial
      stiffness in patients with early rheumatoid arthritis (RA). METHODS: A
      randomized, open-label study in which early RA patients with active disease were
      treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients
      were assessed every 3 months. Patients from the MTX-alone group who failed to
      achieve 28-joint Disease Activity Score remission (DAS28 <= 2.6) at 6 months were
      permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave
      velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months,
      and 12 months. RESULTS: At 6 months, there was a significantly greater reduction
      in PWV in the MTX-alone group (0.18 +/- 1.59 m/s) compared with the MTX plus IFX
      group (-0.78 +/- 1.13 m/s; p = 0.044), accompanied by significantly greater
      reduction in patient's global assessment, number of swollen joints, C-reactive
      protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The
      changes in IMT and AIx were similar between the 2 groups. At 12 months, there was
      a trend favoring early combination treatment with regard to the reduction in PWV
      (p = 0.06). CONCLUSION: MTX plus IFX causes a more significant reduction in PWV
      than MTX alone in patients with early RA after 6-month treatment, and further
      improvement may be achieved in patients who continued on longterm tumor necrosis
      factor-alpha blockers, suggesting that early, effective suppression of
      inflammation may prevent progression of atherosclerosis by improving vascular
      function.

PMID- 22984273
TI  - The Belgian Systemic Sclerosis Cohort: correlations between disease severity
      scores, cutaneous subsets, and autoantibody profile.
AB  - OBJECTIVE: To report baseline and followup data on the first 438 patients with
      systemic sclerosis (SSc) included in the Belgian Systemic Sclerosis Cohort.
      METHODS: According to LeRoy and Medsger's classification, 73 patients with
      limited SSc (lSSc), 279 with limited cutaneous SSc (lcSSc), and 86 with diffuse
      cutaneous SSc (dcSSc) were included. History was collected and clinical
      examination, blood tests, and paraclinical investigations were repeated. The
      Disease Activity Score (DAS) and Disease Severity Score (DSS) of several organ
      systems were computed. An organ system was considered to demonstrate SSc if the
      corresponding DSS was >= 1. RESULTS: At baseline, patients with dcSSc had more
      general, joint/tendon, muscle, gastrointestinal, and kidney involvement. Mean
      DLCO was below normal in patients with lSSc, indicating unsuspected lung
      involvement. Patients with anti-Scl-70 had more vascular, skin, joint/tendon, and
      lung involvement. Patients with anti-RNA polymerase III had more skin and
      joint/tendon involvement compared to patients with anticentromere. Time to death
      was statistically shorter for patients with dcSSc. New-onset lung disease was the
      most common complication over time. No changes in DAS were observed. By contrast,
      the general and the skin DSS worsened in patients with lcSSc and lSSc,
      respectively. Fifteen percent of patients with lSSc shifted to lcSSc at Month 30,
      but neither serology nor capillaroscopy findings at baseline were helpful in
      identifying those at risk. CONCLUSION: Our data indicate that the DSS can be used
      to define organ involvement in SSc. Differences can be seen between subsets
      classified not only according to cutaneous subtypes but also to autoantibody
      profile.

PMID- 22984274
TI  - Major malformations following exposure to nonsteroidal antiinflammatory drugs
      during the first trimester of pregnancy.
AB  - OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAID) are among the most common
      medicines used by pregnant women. Published data are controversial regarding
      fetal safety following intrauterine exposure to NSAID. We investigated exposure
      to NSAID in the first trimester in a large cohort of infants and fetuses.
      METHODS: A computerized database of medications dispensed from 1998 to 2009 to
      all women registered in the "Clalit" health maintenance organization in Southern
      Israel was linked with 2 computerized databases containing maternal and infant
      hospitalization records. Pregnancy terminations for medical reasons were
      analyzed. The following confounders were controlled for: parity, maternal age,
      ethnicity, maternal pregestational diabetes, maternal inflammatory disease, and
      year of birth or pregnancy termination. First trimester exposure to nonselective
      cyclooxygenase (COX) inhibitors and to selective COX-2 inhibitors as groups and
      to individual drugs was analyzed. RESULTS: There were 110,783 pregnancies during
      the study period: 109,544 singleton births and 1239 pregnancy terminations for
      medical reasons. In total, 5267 mothers were exposed to NSAID during the first
      trimester of pregnancy: 5153 to nonselective COX inhibitors and 114 to COX-2
      selective inhibitors. Exposure to NSAID in the first trimester, as groups
      (nonselective COX and selective COX-2 inhibitors) and as individual drugs, was
      not associated with an increased risk of major congenital malformations in
      general (adjusted OR 1.07, 95% CI 0.96-1.21 for nonselective; and adjusted OR
      1.40, 95% CI 0.70-2.78, for selective COX-2 inhibitors), although an increased
      risk for musculoskeletal malformations was found following exposure to COX-2
      selective inhibitors (adjusted OR 3.39, 95% CI 1.37-8.34). CONCLUSION:
      Intrauterine exposure to NSAID was not associated with increased risk for major
      congenital malformations. Further studies are needed to assess the risk for
      malformations after exposure to COX-2 selective inhibitors.

PMID- 22984275
TI  - Prospective study of clinical phenotypes in neuropsychiatric systemic lupus
      erythematosus; multidisciplinary approach to diagnosis and therapy.
AB  - OBJECTIVE: To describe clinical phenotypes in neuropsychiatric systemic lupus
      erythematosus (NPSLE). METHODS: Data were prospectively collected in the Leiden
      NPSLE referral clinic, where patients suspected of having NPSLE are assessed in a
      standardized multidisciplinary manner. In consensus meetings, all medical
      specialists agreed on therapeutic strategy based on the suspected pathogenetic
      mechanism of NPSLE in the individual patient. An algorithm illustrates the
      process of decision-making during the consensus meeting. Clinical phenotypes are
      described, classified by pathogenetic mechanism. RESULTS: One hundred consecutive
      patients were evaluated, of whom 71 had SLE (29 patients did not fulfill >= 4
      American College of Rheumatology criteria) and 46 had NPSLE. Primary NPSLE was
      diagnosed in 38 patients (53%) and could be differentiated in 21 patients (55%)
      with inflammatory NPSLE who were advised on immunosuppressive therapy, 12
      patients (32%) with ischemic NPSLE who were advised on anticoagulant therapy, and
      5 patients (13%) with undefined NPSLE who were advised symptomatic treatment
      only. Cognitive dysfunction and higher level of disease activity were associated
      with inflammatory NPSLE. Although presence of immunoglobulin G anticardiolipin
      antibodies and abnormalities on magnetic resonance imaging (MRI) were associated
      with ischemic NPSLE, abnormalities on MRI lacked specificity to distinguish
      phenotypes. A history of renal disease and use of corticosteroids were associated
      with secondary NPSLE. CONCLUSION: We describe multidisciplinary consensus as a
      standard for diagnosing and defining phenotypes in NPSLE. These phenotypes show
      specific characteristics, which can be used to support diagnosis and guide
      therapeutic decisions. Clinical phenotyping and selection of patients becomes
      increasingly important when advances in experimental science lead to new targets
      for therapy in NPSLE.

PMID- 22984276
TI  - Renal outcome in patients with lupus nephritis using a steroid-free regimen of
      monthly intravenous cyclophosphamide: a prospective observational study.
AB  - OBJECTIVE: Intravenous cyclophosphamide (IV CYC) in combination with high doses
      of corticosteroids is considered the "gold standard" of therapy for lupus
      nephritis (LN). However, the optimal dose of corticosteroids needed has not been
      defined. We evaluated the efficacy of a monotherapy with IV CYC in patients with
      a first episode of LN (duration <= 6 months). METHODS: Forty patients with LN
      received IV CYC (12 pulses). Prednisone alone was administered and dose-adjusted
      to control extrarenal manifestations. Response after 24 months was defined as
      normalization of creatinine level, inactive urinary sediment, and proteinuria <=
      0.2 g/day [complete response (CR)] or <= 0.5 g/day [partial response (PR)].
      RESULTS: CR was achieved in 25 (62.5%) and PR in 8 (20%) patients. Mean starting
      dose of prednisone was 23.9 +/- 23.8 mg/day. In a posthoc analysis, we separately
      analyzed patients initially treated with prednisone doses >= 20 mg/day (Group A,
      n = 19) or < 20 mg/day (Group B, n = 21). CR was achieved in 52.6% (Group A)
      versus 71.4% (Group B; p = 0.37); and PR in 26.3% versus 14.3%, respectively (p =
      0.58). During longterm followup (10.4 +/- 3.1 yrs), 37.8% experienced a renal
      flare. Thirty patients (81%) still have normal renal function. Renal outcome was
      irrespective of initial prednisone doses (p = 0.46, Pearson chi-square test of
      independence). CONCLUSION: Our rates of CR and PR and longterm outcomes were
      comparable with rates after treatment with a combination of IV CYC with high
      doses of corticosteroids. These data warrant randomized controlled trials
      evaluating different doses of corticosteroids in LN.

PMID- 22984277
TI  - Incidence of spondyloarthropathy in patients with Crohn's disease: a population
      based study.
AB  - OBJECTIVE: Spondyloarthritis (SpA) is an extraintestinal manifestation of
      inflammatory bowel disease with significant clinical effects, although the
      frequency is uncertain. We assessed the cumulative incidence and clinical
      spectrum of SpA in patients with Crohn's disease (CD) in a population-based
      cohort. METHODS: The medical records of a population-based cohort of Olmsted
      County, Minnesota, residents diagnosed with CD between 1970 and 2004 were
      reviewed. Patients were followed longitudinally until migration, death, or
      December 31, 2010. We used the European Spondylarthropathy Study Group,
      Assessment of Spondyloarthritis international Society (ASAS) criteria and
      modified New York criteria to identify patients with SpA. The Kaplan-Meier method
      was used to estimate the cumulative incidence of SpA following diagnosis of CD.
      RESULTS: The cohort included 311 patients with CD (49.8% females; median age 29.9
      yrs, range 8-89). Thirty-two patients developed SpA based on ASAS criteria. The
      cumulative incidence of SpA after CD diagnosis was 6.7% (95% CI 2.5%-6.7%) at 10
      years, 13.9% (95% CI 8.7%-18.8%) at 20 years, and 18.6% (95% CI 11.0%-25.5%) at
      30 years. The 10-year cumulative incidence of ankylosing spondylitis was 0, while
      both the 20-year and 30-year cumulative incidences were 0.5% (95% CI 0-1.6%).
      CONCLUSION: We have for the first time defined the actual cumulative incidence of
      SpA in CD using complete medical record information in a population-based cohort.
      The cumulative incidence of all forms of SpA increased to approximately 19% by 30
      years from diagnosis of CD. Our results emphasize the importance of maintaining a
      high level of suspicion for SpA when following patients with CD.

PMID- 22984278
TI  - Source of statistical noises in the Monte Carlo sampling techniques for
      coherently scattered photons.
AB  - Detailed comparisons of the predictions of the Relativistic Form Factors (RFFs)
      and Modified Form Factors (MFFs) and their advantages and shortcomings in
      calculating elastic scattering cross sections can be found in the literature.
      However, the issues related to their implementation in the Monte Carlo (MC)
      sampling for coherently scattered photons is still under discussion. Secondly,
      the linear interpolation technique (LIT) is a popular method to draw the
      integrated values of squared RFFs/MFFs (i.e. A(Z, v(i)2)) over squared momentum
      transfer (v(i)2 = v(1)2,......, v(59)2). In the current study, the role/issues of
      RFFs/MFFs and LIT in the MC sampling for the coherent scattering were analyzed.
      The results showed that the relative probability density curves sampled on the
      basis of MFFs are unable to reveal any extra scientific information as both the
      RFFs and MFFs produced the same MC sampled curves. Furthermore, no relationship
      was established between the multiple small peaks and irregular step shapes (i.e.
      statistical noise) in the PDFs and either RFFs or MFFs. In fact, the noise in the
      PDFs appeared due to the use of LIT. The density of the noise depends upon the
      interval length between two consecutive points in the input data table of A(Z,
      v(i)2) and has no scientific background. The probability density function curves
      became smoother as the interval lengths were decreased. In conclusion, these
      statistical noises can be efficiently removed by introducing more data points in
      the A(Z, v(i)2) data tables.

PMID- 22984279
TI  - Radio-protective effect of catalpol in cultured cells and mice.
AB  - Ionizing radiation can induce DNA damage and cell death by generating reactive
      oxygen species (ROS). The objective of this study was to investigate the radio
      protective effect of catalpol (a main bioactive component in the traditional
      Chinese Rehmannia) on irradiated cells and mice. We found that treating cells
      with catalpol (25-100 MUg/ml) before irradiation could significantly inhibit
      ionizing radiation (IR)-induced human lymphocyte AHH-1 cells apoptosis and
      increase cells viability in vitro. At the same time our study also showed that
      catalpol (25-100 mg/kg) reduced morphological damage of the gastrointestinal
      tract by 15.6%, 33.3% and 44.4%, respectively compared with the radiation-induced
      group, decreased plasma malondialdehyde (MDA) intestinal 8-hydroxydeoxyguanosine
      (8-OHdG) levels and increased plasma endogenous antioxidants and peripheral white
      blood cells and platelets in vivo. These results suggest that catalpol possesses
      notable radio-protective activity, which might be related to its effect of
      reducing ROS.

PMID- 22984280
TI  - Differences in the dose-volume metrics with heterogeneity correction status and
      its influence on local control in stereotactic body radiation therapy for lung
      cancer.
AB  - The purpose of this study is to evaluate the dose-volume metrics under different
      heterogeneity corrections and the factors associated with local recurrence (LR)
      after stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer
      (NSCLC). Eighty-three patients who underwent SBRT for pathologically proven stage
      I NSCLC were reviewed retrospectively. The prescribed dose was 48 Gy in four
      fractions at the isocenter (IC) under heterogeneity correction with the Batho
      power law (BPL). The clinical plans were recalculated with Eclipse (Varian) for
      the same monitor units under the BPL and anisotropic analytical algorithm (AAA)
      and with no heterogeneity correction (NC). The dose at the IC, dose that covers
      95% of the volume (D95), minimum dose (Min), and mean dose (Mean) of the planning
      target volume (PTV) were compared under each algorithm and between patients with
      local lesion control (LC) and LR. The IC doses under NC were significantly lower
      than those under the BPL and AAA. Under the BPL, the mean PTV D95, Min and Mean
      were 8.0, 9.4 and 7.4% higher than those under the AAA, and 9.6, 9.2 and 4.6%
      higher than those under NC, respectively. Under the AAA, all dose-volumetric
      parameters were significantly lower in T1a patients than in those with T1b and
      T2a. With a median follow-up of 35.9 months, LR occurred in 18 patients. Between
      the LC and LR groups, no significant differences were observed for any of the
      metrics. Even after stratification according to T-stage, no significant
      difference was observed between LC and LR.

PMID- 22984281
TI  - Spontaneous object recognition memory in aged rats: Complexity versus similarity.
AB  - Previous work on the effect of aging on spontaneous object recognition (SOR)
      memory tasks in rats has yielded controversial results. Although the results at
      long-retention intervals are consistent, conflicting results have been reported
      at shorter delays. We have assessed the potential relevance of the type of object
      used in the performance of aged rats in SOR tasks. Using standard objects, 24-mo
      old rats did not exhibit retention impairment at a 1-h delay. At this retention
      interval no differences between young and old rats were found in a high
      similarity SOR task, but aged rats exhibited deficits when clearly different
      complex forms were applied.

PMID- 22984282
TI  - Involvement of the anterior cingulate cortex in formation, consolidation, and
      reconsolidation of recent and remote contextual fear memory.
AB  - It has been suggested that memories become more stable and less susceptible to
      the disruption of reconsolidation over weeks after learning. Here, we test this
      by targeting the anterior cingulate cortex (ACC) and test its involvement in the
      formation, consolidation, and reconsolidation of recent and remote contextual
      fear memory. We found that inhibiting NMDAR-NR2B activity disrupts memory
      formation, and that infusion of the protein-synthesis inhibitor anisomycin
      impairs memory consolidation and reconsolidation of recent and remote memory. Our
      findings demonstrate for the first time that the ACC plays an important role in
      reconsolidation of contextual fear memory at recent and remote time points.

PMID- 22984283
TI  - Restoration of dopamine release deficits during object recognition memory
      acquisition attenuates cognitive impairment in a triple transgenic mice model of
      Alzheimer's disease.
AB  - Previous findings indicate that the acquisition and consolidation of recognition
      memory involves dopaminergic activity. Although dopamine deregulation has been
      observed in Alzheimer's disease (AD) patients, the dysfunction of this
      neurotransmitter has not been investigated in animal models of AD. The aim of
      this study was to assess, by in vivo microdialysis, cortical and hippocampal
      dopamine, norepinephrine, and glutamate release during the acquisition of object
      recognition memory (ORM) in 5- and 10-mo-old triple-transgenic Alzheimer's
      disease mice (3xTg-AD) and to relate the extracellular changes to 24-h memory
      performance. Five- and 10-mo-old wild-type mice and 5-mo-old 3xTg-AD showed
      significant cortical but not hippocampal dopamine increase during object
      exploration. On a 24-h ORM test, these three groups displayed significant ORM. In
      contrast, 10-mo-old 3xTg-AD mice showed impaired dopamine release in the insular
      cortex during ORM acquisition, as well as significant impairment in ORM. In
      addition, cortical administration of a dopamine reuptake blocker produced an
      increase of dopamine levels in the 10-mo-old 3xTg-AD mice and attenuated the
      memory impairment. These data suggest that activation of the dopaminergic system
      in the insular cortex is involved in object recognition memory, and that
      dysfunction of this system contributes to the age-related decline in cognitive
      functioning of the 3xTg-AD mice.

PMID- 22984284
TI  - D-cycloserine does not facilitate fear extinction by reducing conditioned
      stimulus processing or promoting conditioned inhibition to contextual cues.
AB  - The NMDA receptor partial agonist d-cycloserine (DCS) enhances the extinction of
      learned fear in rats and exposure therapy in humans with anxiety disorders.
      Despite these benefits, little is known about the mechanisms by which DCS
      promotes the loss of fear. The present study examined whether DCS augments
      extinction retention (1) through reductions in conditioned stimulus (CS)
      processing or (2) by promoting the development of conditioned inhibition to
      contextual cues. Rats administered DCS prior to extinction showed enhanced long
      term extinction retention (Experiments 3 and 4). The same nonreinforced CS
      procedure used in extinction also reduced freezing at test when presented as pre
      exposure before conditioning, demonstrating latent inhibition (Experiment 1). DCS
      administered shortly prior to pre-exposure had no effect on latent inhibition
      using parameters which produced weak (Experiment 2) or strong (Experiment 3)
      expression of latent inhibition. Therefore, DCS facilitated learning involving CS
      alone exposures, but only when these exposures occurred after (extinction) and
      not before (latent inhibition) conditioning. We also used a retardation test
      procedure to examine whether the extinction context gained inhibitory properties
      for rats given DCS prior to extinction. With three different footshock
      intensities, there was no evidence that DCS promoted accrual of associative
      inhibition to the extinction context (Experiment 4). The present findings
      demonstrate that DCS does not facilitate extinction by reducing CS processing or
      causing the extinction context to become a conditioned inhibitor. Investigations
      into the mechanisms underlying the augmentation of extinction by DCS are valuable
      for understanding how fear can be inhibited.

PMID- 22984285
TI  - Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL)
      deficiencies affect expression of lipolytic activities in mouse adipose tissues.
AB  - Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key
      enzymes involved in intracellular degradation of triacylglycerols. It was the aim
      of this study to elucidate how the deficiency in one of these proteins affects
      the residual lipolytic proteome in adipose tissue. For this purpose, we compared
      the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/
      ) mice using differential activity-based gel electrophoresis. This method is
      based on activity-recognition probes possessing the same substrate analogous
      structure but carrying different fluorophores for specific detection of the
      enzyme patterns of two different tissues in one electrophoresis gel. We found
      that ATGL-deficiency in brown adipose tissue had a profound effect on the
      expression levels of other lipolytic and esterolytic enzymes in this tissue,
      whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither
      ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose
      tissue. Enzyme activities of mouse tissues on acylglycerol substrates were
      analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for
      at least in part by other enzymes. The proteins that responded to ATGL-deficiency
      in brown adipose tissue were overexpressed and their activities on acylglycerols
      were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase
      candidates as they catalyze the hydrolysis of long-chain acylglycerols.

PMID- 22984286
TI  - High-resolution mapping of linear antibody epitopes using ultrahigh-density
      peptide microarrays.
AB  - Antibodies empower numerous important scientific, clinical, diagnostic, and
      industrial applications. Ideally, the epitope(s) targeted by an antibody should
      be identified and characterized, thereby establishing antibody reactivity,
      highlighting possible cross-reactivities, and perhaps even warning against
      unwanted (e.g. autoimmune) reactivities. Antibodies target proteins as either
      conformational or linear epitopes. The latter are typically probed with peptides,
      but the cost of peptide screening programs tends to prohibit comprehensive
      specificity analysis. To perform high-throughput, high-resolution mapping of
      linear antibody epitopes, we have used ultrahigh-density peptide microarrays
      generating several hundred thousand different peptides per array. Using
      exhaustive length and substitution analysis, we have successfully examined the
      specificity of a panel of polyclonal antibodies raised against linear epitopes of
      the human proteome and obtained very detailed descriptions of the involved
      specificities. The epitopes identified ranged from 4 to 12 amino acids in size.
      In general, the antibodies were of exquisite specificity, frequently disallowing
      even single conservative substitutions. In several cases, multiple distinct
      epitopes could be identified for the same target protein, suggesting an efficient
      approach to the generation of paired antibodies. Two alternative epitope mapping
      approaches identified similar, although not necessarily identical, epitopes.
      These results show that ultrahigh-density peptide microarrays can be used for
      linear epitope mapping. With an upper theoretical limit of 2,000,000 individual
      peptides per array, these peptide microarrays may even be used for a systematic
      validation of antibodies at the proteomic level.

PMID- 22984287
TI  - The effect of long term calorie restriction on in vivo hepatic proteostatis: a
      novel combination of dynamic and quantitative proteomics.
AB  - Calorie restriction (CR) promotes longevity. A prevalent mechanistic hypothesis
      explaining this effect suggests that protein degradation, including mitochondrial
      autophagy, is increased with CR, removing damaged proteins and improving cellular
      fitness. At steady state, increased catabolism must be balanced by increasing
      mitochondrial biogenesis and protein synthesis, resulting in faster protein
      replacement rates. To test this hypothesis, we measured replacement kinetics and
      relative concentrations of hundreds of proteins in vivo in long-term CR and ad
      libitum-fed mice using metabolic (2)H(2)O-labeling combined with the Stable
      Isotope Labeling in Mammals protocol and LC-MS/MS analysis of mass isotopomer
      abundances in tryptic peptides. CR reduced absolute synthesis and breakdown rates
      of almost all measured hepatic proteins and prolonged the half-lives of most (~
      80%), particularly mitochondrial proteins (but not ribosomal subunits). Proteins
      with related functions exhibited coordinated changes in relative concentration
      and replacement rates. In silico expression pathway interrogation allowed the
      testing of potential regulators of altered network dynamics (e.g. peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha). In summary, our
      combination of dynamic and quantitative proteomics suggests that long-term CR
      reduces mitochondrial biogenesis and mitophagy. Our findings contradict the
      theory that CR increases mitochondrial protein turnover and provide compelling
      evidence that cellular fitness is accompanied by reduced global protein synthetic
      burden.

PMID- 22984288
TI  - Human family with sequence similarity 60 member A (FAM60A) protein: a new subunit
      of the Sin3 deacetylase complex.
AB  - Here we describe the function of a previously uncharacterized protein, named
      family with sequence similarity 60 member A (FAM60A) that maps to chromosome
      12p11 in humans. We use quantitative proteomics to determine that the main
      biochemical partners of FAM60A are subunits of the Sin3 deacetylase complex and
      show that FAM60A resides in active HDAC complexes. In addition, we conduct gene
      expression pathway analysis and find that FAM60A regulates expression of genes
      that encode components of the TGF-beta signaling pathway. Moreover, our studies
      reveal that loss of FAM60A or another component of the Sin3 complex, SDS3, leads
      to a change in cell morphology and an increase in cell migration. These studies
      reveal the function of a previously uncharacterized protein and implicate the
      Sin3 complex in suppressing cell migration.

PMID- 22984290
TI  - Targeted proteomics of the secretory pathway reveals the secretome of mouse
      embryonic fibroblasts and human embryonic stem cells.
AB  - Proteins endogenously secreted by human embryonic stem cells (hESCs) and those
      present in hESC culture medium are critical regulators of hESC self-renewal and
      differentiation. Current MS-based approaches for identifying secreted proteins
      rely predominantly on MS analysis of cell culture supernatants. Here we show that
      targeted proteomics of secretory pathway organelles is a powerful alternate
      approach for interrogating the cellular secretome. We have developed procedures
      to obtain subcellular fractions from mouse embryonic fibroblasts (MEFs) and hESCs
      that are enriched in secretory pathway organelles while ensuring retention of the
      secretory cargo. MS analysis of these fractions from hESCs cultured in MEF
      conditioned medium (MEF-CM) or MEFs exposed to hESC medium revealed 99 and 129
      proteins putatively secreted by hESCs and MEFs, respectively. Of these, 53 and 62
      proteins have been previously identified in cell culture supernatants of MEFs and
      hESCs, respectively, thus establishing the validity of our approach. Furthermore,
      76 and 37 putatively secreted proteins identified in this study in MEFs and
      hESCs, respectively, have not been reported in previous MS analyses. The
      identification of low abundance secreted proteins via MS analysis of cell culture
      supernatants typically necessitates the use of altered culture conditions such as
      serum-free medium. However, an altered medium formulation might directly
      influence the cellular secretome. Indeed, we observed significant differences
      between the abundances of several secreted proteins in subcellular fractions
      isolated from hESCs cultured in MEF-CM and those exposed to unconditioned hESC
      medium for 24 h. In contrast, targeted proteomics of secretory pathway organelles
      does not require the use of customized media. We expect that our approach will be
      particularly valuable in two contexts highly relevant to hESC biology: obtaining
      a temporal snapshot of proteins secreted in response to a differentiation
      trigger, and identifying proteins secreted by cells that are isolated from a
      heterogeneous population.

PMID- 22984291
TI  - Adolescent alcohol use, sociability and income as a young adult.
AB  - We use data from the National Longitudinal Survey of Adolescent Health (Add
      Health) to study how sociability and adolescent alcohol use impact personal
      income as a young adult. We find that factors which enhance not only individual
      sociability but also social interaction at the community level are positively
      linked to future earnings of adolescents. Adolescents whose friends and friends
      of friends have greater sociability reap long-term labor market rewards into
      adulthood. After adjusting for individual and community sociability, the effect
      of teenage alcohol consumption on labor market earnings as young adults is
      reduced. Our results suggest that earnings premiums associated with adolescent
      alcohol consumption may be partially explained by social network dynamics.

PMID- 22984289
TI  - Intermembrane space proteome of yeast mitochondria.
AB  - The intermembrane space (IMS) represents the smallest subcompartment of
      mitochondria. Nevertheless, it plays important roles in the transport and
      modification of proteins, lipids, and metal ions and in the regulation and
      assembly of the respiratory chain complexes. Moreover, it is involved in many
      redox processes and coordinates key steps in programmed cell death. A
      comprehensive profiling of IMS proteins has not been performed so far. We have
      established a method that uses the proapoptotic protein Bax to release IMS
      proteins from isolated mitochondria, and we profiled the protein composition of
      this compartment. Using stable isotope-labeled mitochondria from Saccharomyces
      cerevisiae, we were able to measure specific Bax-dependent protein release and
      distinguish between quantitatively released IMS proteins and the background
      efflux of matrix proteins. From the known 31 soluble IMS proteins, 29 proteins
      were reproducibly identified, corresponding to a coverage of >90%. In addition,
      we found 20 novel intermembrane space proteins, out of which 10 had not been
      localized to mitochondria before. Many of these novel IMS proteins have unknown
      functions or have been reported to play a role in redox regulation. We confirmed
      IMS localization for 15 proteins using in organello import, protease
      accessibility upon osmotic swelling, and Bax-release assays. Moreover, we
      identified two novel mitochondrial proteins, Ymr244c-a (Coa6) and Ybl107c
      (Mic23), as substrates of the MIA import pathway that have unusual cysteine
      motifs and found the protein phosphatase Ptc5 to be a novel substrate of the
      inner membrane protease (IMP). For Coa6 we discovered a role as a novel assembly
      factor of the cytochrome c oxidase complex. We present here the first and
      comprehensive proteome of IMS proteins of yeast mitochondria with 51 proteins in
      total. The IMS proteome will serve as a valuable source for further studies on
      the role of the IMS in cell life and death.

PMID- 22984293
TI  - Transnational labour migration and the politics of care in the Southeast Asian
      family.
AB  - Recent increases in female labour migration in and from Asia have triggered a
      surge of interest in how the absence of the mother and wife for extended periods
      of time affects the left-behind family, particularly children, in labour-sending
      countries. While migration studies in the region have shown that the extended
      family, especially female relatives, is often called on for support in childcare
      during the mother's absence it is not yet clear how childcare arrangements are
      made. Drawing on in-depth interviews with non-parent carers of left-behind
      children in Indonesia and Vietnam, the paper aims to unveil complexities and
      nuances around care in the context of transnational labour migration. In so doing
      it draws attention to the enduring influence of social norms on the organisation
      of family life when women are increasingly drawn into the global labour market.
      By contrasting a predominantly patrilineal East Asian family structure in Vietnam
      with what is often understood as a bilateral South-East Asian family structure in
      Indonesia, the paper seeks to provide interesting comparative insights into the
      adaptive strategies that the transnational family pursues in order to cope with
      the reproductive vacuum left behind by the migrant mother.

PMID- 22984292
TI  - Health and labor supply in the context of HIV/AIDS: the long-run economic impacts
      on antiretroviral therapy().
AB  - Using longitudinal survey data collected in Kenya, this paper estimates the
      longer-term impacts of antiretroviral therapy (ART) on the labor supply of
      treated adults and their household members. Building upon previous work in Kenya,
      data collected from 2004-2006 indicate that early evidence on the short-run
      impacts of ART tends to be upheld over the long-term as well. The results show
      that the labor supply response among treated adults occurs rapidly and is
      sustained through the 3-year observation period in our study. These results
      underscore the strong relationship between health and labor supply that has been
      observed in other contexts.

PMID- 22984294
TI  - Implementation of adolescent family-based substance use prevention programs in
      health care settings: Comparisons across conditions and programs.
AB  - BACKGROUND: The majority of knowledge related to implementation of family-based
      substance use prevention programs is based on programs delivered in school and
      community settings. The aim of this study is to examine procedures related to
      implementation effectiveness and quality of two family-based universal substance
      use prevention programs delivered in health care settings, the Strengthening
      Families Program: For Parents and Youth 10-14 (SFP) and Family Matters (FM).
      These evidence-based programs were delivered as part of a larger random control
      intervention study designed to assess the influence of program choice vs.
      assignment on study participation and adolescent substance use outcomes. We also
      assess the effects of program choice (vs. assignment to program) on program
      delivery.  METHODS: A mixed method case study was conducted to assess procedures
      used to maximize implementation quality and fidelity of family-based prevention
      programs delivered in health care settings. Families with an 11 year old child
      were randomly selected for study participation from health plan membership
      databases of 4 large urban medical centers in the San Francisco Bay Area.
      Eligible families were initially randomized to a Choice study condition (families
      choose SFP or FM) or Assigned study condition (assigned to FM, SFP or control
      group); 494 ethnically diverse families were selected for participation in study
      programs.  RESULTS: Successful implementation of family prevention programs in
      health care settings required knowledge of the health care environment and
      familiarity with established procedures for developing ongoing support and
      collaboration. Ongoing training of program deliverers utilizing data from
      fidelity assessment appeared to contribute to improved program fidelity over the
      course of the study. Families who chose FM completed the program in a shorter
      period (p<.0001) and spent more time implementing program activities (p=0.02)
      compared to families assigned to FM. SFP "choice" families attended more sessions
      than those assigned to SFP (3.5 vs. 2.8), (p=0.07).  CONCLUSION: Program choice
      appeared to increase family engagement in programs. The goals and approach of
      universal family-based substance use prevention programs are congruent with the
      aims and protocols of adolescent preventive health care services. Future
      effectiveness trials should assess approaches to integrate evidence-based family
      prevention programs with adolescent health services.

PMID- 22984295
TI  - Strong consistency of nonparametric Bayes density estimation on compact metric
      spaces with applications to specific manifolds.
AB  - This article considers a broad class of kernel mixture density models on compact
      metric spaces and manifolds. Following a Bayesian approach with a nonparametric
      prior on the location mixing distribution, sufficient conditions are obtained on
      the kernel, prior and the underlying space for strong posterior consistency at
      any continuous density. The prior is also allowed to depend on the sample size n
      and sufficient conditions are obtained for weak and strong consistency. These
      conditions are verified on compact Euclidean spaces using multivariate Gaussian
      kernels, on the hypersphere using a von Mises-Fisher kernel and on the planar
      shape space using complex Watson kernels.

PMID- 22984296
TI  - Serving God and Country? Religious Involvement and Military Service among Young
      Adult Men.
AB  - Despite important connections between religion and military action throughout
      world history, scholars have seldom explored the association between religiosity
      and military enlistment. Using data from the National Longitudinal Study of
      Adolescent Health (Add Health), we used a person-oriented analysis to categorize
      young men according to patterns of adolescent religious involvement. Youth
      indentified as "highly religious evangelical" are more likely to enlist in the
      military compared to their "highly religious non-evangelical" and "non-religious"
      counterparts; however, these findings hold only for those young men without
      college experience. These findings are discussed along with study limitations and
      promising directions for future research.

PMID- 22984297
TI  - Effective psychotherapy with low-income clients: The importance of attending to
      social class.
AB  - The purpose of this article is to explore some of the issues associated with
      conducting psychotherapy with low-income clients. Throughout the article, we draw
      from our specific clinical experiences working with low-income Latina mothers in
      a depression prevention program. The themes that we address regarding class and
      psychotherapy are in the areas of assessment of social class, integration of
      class issues into the therapy process, and managing differences in social class
      between therapists and clients. As we discuss these themes, we provide concrete
      recommendations in order to advance awareness and effectiveness in working with
      economically disadvantaged populations.

PMID- 22984298
TI  - Resisting Weakness of the Will.
AB  - I develop an account of weakness of the will that is driven by experimental
      evidence from cognitive and social psychology. I will argue that this account
      demonstrates that there is no such thing as weakness of the will: no
      psychological kind corresponds to it. Instead, weakness of the will ought to be
      understood as depletion of System II resources. Neither the explanatory purposes
      of psychology nor our practical purposes as agents are well-served by retaining
      the concept. I therefore suggest that we ought to jettison it, in favour of the
      vocabulary and concepts of cognitive psychology.

PMID- 22984299
TI  - Pores and Void in Asclepiades' Physical Theory.
AB  - This paper examines a fundamental, though relatively understudied, aspect of the
      physical theory of the physician Asclepiades of Bithynia, namely his doctrine of
      pores. My principal thesis is that this doctrine is dependent on a conception of
      void taken directly from Epicurean physics. The paper falls into two parts: the
      first half addresses the evidence for the presence of void in Asclepiades'
      theory, and concludes that his conception of void was basically that of Epicurus;
      the second half focuses on the precise nature of Asclepiadean pores, and seeks to
      show that they represent void interstices between the primary particles of matter
      which are the constituents of the human body, and are thus exactly analogous to
      the void interstices between atoms within solid objects in Epicurus' theory.

PMID- 22984300
TI  - o-(Trialkylstannyl)anilines and Their Utility in Stille Cross-Coupling: Direct
      Introduction of the 2-Aminophenyl Substituent.
AB  - We have developed shelf- and air-stable ortho-stannylated aniline reagents that
      can directly be coupled with alkenyl and aryl halides via Stille cross-coupling.
      We report i) the efficient preparation of o-(tributylstannyl)aniline (2a) and o
      (trimethylstannyl)aniline (2b), ii) the comparison of the reactivities of 2a and
      2b with those of related organostannanes in cross-coupling reaction with an
      alkenyl halide, and iii) the cross-coupling of 2a and 2b with a series of
      arylhalides and triflate.

PMID- 22984302
TI  - "E" is for everything else, not least for expanding HIV testing in Europe.

PMID- 22984303
TI  - Bridging the gap from knowledge to delivery in the control of childhood
      diarrhoea.

PMID- 22984305
TI  - Clipping the wings of avian influenza.
AB  - Up to now, the threat of avian influenza has been lessened by effective animal
      husbandry methods. However, the public health community is trying to ensure
      enough measures are in place to prevent a possible pandemic. Jane Parry reports.

PMID- 22984306
TI  - The fight to stub out tobacco.
AB  - Dr Jeffrey Wigand is delivering an anti-smoking message to children and young
      people. He talked to Ben Jones about his work.

PMID- 22984308
TI  - Male circumcision programmes in Kenya: lessons from the Kenya AIDS Indicator
      Survey 2007.
AB  - OBJECTIVE: To provide guidance for male circumcision programmes in Kenya by
      estimating the population of uncircumcised men and investigating the association
      between circumcision and infection with the human immunodeficiency virus (HIV),
      with particular reference to uncircumcised, HIV-uninfected men. METHODS: Data on
      men aged 15 to 64 years were derived from the 2007 Kenya AIDS Indicator Survey,
      which involved interviews and blood collection to test for HIV and herpes simplex
      virus 2 (HSV-2). The prevalence of HIV infection and circumcision in Kenyan
      provinces was calculated and the demographic characteristics and sexual behaviour
      of circumcised and uncircumcised, HIV-infected and HIV-uninfected men were
      recorded. FINDINGS: The national prevalence of HIV infection in uncircumcised men
      was 13.2% (95% confidence interval, CI: 10.8-15.7) compared with 3.9% (95% CI:
      3.3-4.5) among circumcised men. Nyanza province had the largest estimated number
      of uncircumcised, HIV-uninfected men (i.e. 601 709), followed by Rift Valley,
      Nairobi and Western Province, respectively, and most belonged to the Luo ethnic
      tribe. Of these men, 77.8% did not know their HIV status and 33.2% were HSV-2
      positive. In addition, 65.3% had had unprotected sex with a partner of discordant
      or unknown HIV status in the past 12 months and only 14.7% consistently used
      condoms with their most recent partner. However, only 21.8% of the uncircumcised,
      HIV-uninfected men aged 15 to 19 years were sexually active. CONCLUSION: The
      Kenyan male circumcision strategy should focus on the provinces with the highest
      number of uncircumcised, HIV-uninfected men and target young men before or
      shortly after sexual debut.

PMID- 22984309
TI  - From caution to urgency: the evolution of HIV testing and counselling in Africa.
AB  - OBJECTIVE: To describe recent changes in policy on provider-initiated testing and
      counselling (PITC) for human immunodeficiency virus (HIV) infection in African
      countries and to investigate patients' experiences of and views about PITC.
      METHODS: A review of the published literature and of national HIV testing
      policies, strategic frameworks, plans and other relevant documents was carried
      out. FINDINGS: Of the African countries reviewed, 42 (79.2%) had adopted a PITC
      policy. Of the 42, all recommended PITC for the prevention of mother-to-child HIV
      transmission, 66.7% recommended it for tuberculosis clinics and patients, and
      45.2% for sexually transmitted infection clinics. Moreover, 43.6% adopted PITC in
      2005 or 2006. The literature search identified 11 studies on patients'
      experiences of and views about PITC in clinical settings in Africa. The clear
      majority regarded PITC as acceptable. However, women in antenatal clinics were
      not always aware that they had the right to decline an HIV test. CONCLUSION:
      Policy and practice on HIV testing and counselling in Africa has shifted from a
      cautious approach that emphasizes confidentiality to greater acceptance of the
      routine offer of HIV testing. The introduction of PITC in clinical settings has
      contributed to increased HIV testing in several of these settings. Most patients
      regard PITC as acceptable. However, other approaches are needed to reach people
      who do not consult health-care services.

PMID- 22984310
TI  - Implications of adopting new WHO guidelines for antiretroviral therapy initiation
      in Ethiopia.
AB  - OBJECTIVE: To assess the implications of implementing the World Health
      Organization (WHO) 2010 guidelines for antiretroviral therapy (ART) initiation in
      adults and adolescents with human immunodeficiency virus (HIV) infection, which
      recommend initiating ART at a CD4+ T lymphocyte (CD4+) threshold of <= 350
      cells/mm(3) instead of <= 200 cells/mm(3), which was the earlier threshold.
      METHODS: Between April and May 2010, CD4+ test results were collected for all HIV
      infected patients recorded in the pre-ART and ART registers of 19 high-patient
      load health centres in Addis Ababa, Ethiopia, and the regions of Amhara, Oromia,
      SNNPR (Southern Nations, Nationalities and People's Region) and Tigray. At 12
      centres patient records were independently reviewed to assess data accuracy. To
      estimate the total number of patients who would need ART at health centres if
      Ethiopia adopted the new WHO guidelines, the number of patients needing ART based
      on current guidelines were added to the number of asymptomatic patients enrolled
      in pre-ART with a CD4+ count > 200 but <= 350 cells/mm(3) FINDINGS: Adoption of
      the new WHO guidelines would increase the total number of patients on ART in the
      19 health centres in Ethiopia by about 30%: from 3583 to 4640. CONCLUSION: The
      shift in the CD4+ threshold for ART initiation will substantially increase the
      demand for ART in Ethiopia. Since under the current systems only 60% of
      Ethiopia's patients in need of ART are receiving the medications, scaling up ART
      programmes to accommodate the increased demand for drugs will not be possible
      unless government funding and support increase concurrently.

PMID- 22984311
TI  - Factors affecting catastrophic health expenditure and impoverishment from medical
      expenses in China: policy implications of universal health insurance.
AB  - OBJECTIVE: To assess the degree to which the Chinese people are protected from
      catastrophic household expenditure and impoverishment from medical expenses and
      to explore the health system and structural factors influencing the first of
      these outcomes. METHODS: Data were derived from the Fourth National Health
      Service Survey. An analysis of catastrophic health expenditure and impoverishment
      from medical expenses was undertaken with a sample of 55 556 households of
      different characteristics and located in rural and urban settings in different
      parts of the country. Logistic regression was used to identify the determinants
      of catastrophic health expenditure. FINDINGS: The rate of catastrophic health
      expenditure was 13.0%; that of impoverishment was 7.5%. Rates of catastrophic
      health expenditure were higher among households having members who were
      hospitalized, elderly, or chronically ill, as well as in households in rural or
      poorer regions. A combination of adverse factors increased the risk of
      catastrophic health expenditure. Families enrolled in the urban employee or
      resident insurance schemes had lower rates of catastrophic health expenditure
      than those enrolled in the new rural corporative scheme. The need for and use of
      health care, demographics, type of benefit package and type of provider payment
      method were the determinants of catastrophic health expenditure. CONCLUSION:
      Although China has greatly expanded health insurance coverage, financial
      protection remains insufficient. Policy-makers should focus on designing improved
      insurance plans by expanding the benefit package, redesigning cost sharing
      arrangements and provider payment methods and developing more effective
      expenditure control strategies.

PMID- 22984312
TI  - Strategies for delivering insecticide-treated nets at scale for malaria control:
      a systematic review.
AB  - OBJECTIVE: To synthesize findings from recent studies of strategies to deliver
      insecticide-treated nets (ITNs) at scale in malaria-endemic areas. METHODS:
      Databases were searched for studies published between January 2000 and December
      2010 in which: subjects resided in areas with endemicity for Plasmodium
      falciparum and Plasmodium vivax malaria; ITN delivery at scale was evaluated; ITN
      ownership among households, receipt by pregnant women and/or use among children
      aged < 5 years was evaluated; and the study design was an individual or cluster
      randomized controlled design, nonrandomized, quasi-experimental, before-and
      after, interrupted time series or cross-sectional without temporal or
      geographical controls. Papers describing qualitative studies, case studies,
      process evaluations and cost-effectiveness studies linked to an eligible paper
      were also included. Study quality was assessed using the Cochrane risk of bias
      checklist and GRADE criteria. Important influences on scaling up were identified
      and assessed across delivery strategies. FINDINGS: A total of 32 papers
      describing 20 African studies were reviewed. Many delivery strategies involved
      health sectors and retail outlets (partial subsidy), antenatal care clinics (full
      subsidy) and campaigns (full subsidy). Strategies achieving high ownership among
      households and use among children < 5 delivered ITNs free through campaigns.
      Costs were largely comparable across strategies; ITNs were the main cost. Cost
      effectiveness estimates were most sensitive to the assumed net lifespan and
      leakage. Common barriers to delivery included cost, stock-outs and poor
      logistics. Common facilitators were staff training and supervision, cooperation
      across departments or ministries and stakeholder involvement. CONCLUSION: There
      is a broad taxonomy of strategies for delivering ITNs at scale.

PMID- 22984313
TI  - The impact of health insurance in Africa and Asia: a systematic review.
AB  - OBJECTIVE: To evaluate the impact of health insurance on resource mobilization,
      financial protection, service utilization, quality of care, social inclusion and
      community empowerment in low- and lower-middle-income countries in Africa and
      Asia. METHODS: A systematic search for randomized controlled trials, quasi
      experimental and observational studies published before the end of 2011 was
      conducted in 20 literature databases, reference lists of relevant studies, web
      sites and the grey literature. Study quality was assessed with a quality grading
      protocol. FINDINGS: Inclusion criteria were met by 159 studies - 68 in Africa and
      91 in Asia. Most African studies reported on community-based health insurance
      (CBHI) and were of relatively high quality; social health insurance (SHI) studies
      were mostly Asian and of medium quality. Only one Asian study dealt with private
      health insurance (PHI). Most studies were observational; four had randomized
      controls and 20 had a quasi-experimental design. Financial protection,
      utilization and social inclusion were far more common subjects than resource
      mobilization, quality of care or community empowerment. Strong evidence shows
      that CBHI and SHI improve service utilization and protect members financially by
      reducing their out-of-pocket expenditure, and that CBHI improves resource
      mobilization too. Weak evidence points to a positive effect of both SHI and CBHI
      on quality of care and social inclusion. The effect of SHI and CBHI on community
      empowerment is inconclusive. Findings for PHI are inconclusive in all domains
      because of insufficient studies. CONCLUSION: Health insurance offers some
      protection against the detrimental effects of user fees and a promising avenue
      towards universal health-care coverage.

PMID- 22984314
TI  - Challenging a dogma: antimicrobial susceptibility testing breakpoints for
      Mycobacterium tuberculosis.
AB  - The rise in multidrug-resistant tuberculosis makes it increasingly important that
      antimicrobial susceptibility testing of Mycobacterium tuberculosis produce
      clinically meaningful and technically reproducible results. Unfortunately, this
      is not always the case because mycobacteriology specialists have not followed
      generally accepted modern principles for the establishment of susceptibility
      breakpoints for bacterial and fungal pathogens. These principles specifically
      call for a definition of the minimum inhibitory concentrations (MICs) applicable
      to organisms without resistance mechanisms (also known as wild-type MIC
      distributions), to be used in combination with data on clinical outcomes,
      pharmacokinetics and pharmacodynamics. In a series of papers the authors have
      defined tentative wild-type MIC distributions for M. tuberculosis and hope that
      other researchers will follow their example and provide confirmatory data. They
      suggest that some breakpoints are in need of revision because they either (i)
      bisect the wild-type distribution, which leads to poor reproducibility in
      antimicrobial susceptibility testing, or (ii) are substantially higher than the
      MICs of wild-type organisms without supporting clinical evidence, which may
      result in some strains being falsely reported as susceptible. The authors
      recommend, in short, that susceptibility breakpoints for antituberculosis agents
      be systematically reviewed and revised, if necessary, using the same modern tools
      now accepted for all other bacteria and fungi by the scientific community and by
      the European Medicines Agency and the European Centre for Disease Prevention and
      Control. For several agents this would greatly improve the accuracy and
      reproducibility of antimicrobial susceptibility testing of M. tuberculosis.

PMID- 22984316
TI  - Feasibility of using teleradiology to improve tuberculosis screening and case
      management in a district hospital in Malawi.
AB  - PROBLEM: Malawi has one of the world's highest rates of human immunodeficiency
      virus (HIV) infection (10.6%), and southern Malawi, where Thyolo district is
      located, bears the highest burden in the country (14.5%). Tuberculosis, common
      among HIV-infected people, requires radiologic diagnosis, yet Malawi has no
      radiologists in public service. This hinders rapid and accurate diagnosis and
      increases morbidity and mortality. APPROACH: Medecins Sans Frontieres, in
      collaboration with Malawi's Ministry of Health, implemented teleradiology in
      Thyolo district to assist clinical staff in radiologic image interpretation and
      diagnosis. LOCAL SETTING: Thyolo district's 600 000 inhabitants are mostly
      subsistence-level or migrant farmers living in extreme poverty. Health facilities
      include one public hospital and 38 primary health centres. Understaffing and the
      absence of a radiologist make the diagnosis of tuberculosis difficult in a
      population where this disease affects 66% of patients with HIV infection.
      RELEVANT CHANGES: From September 2010-2011, 159 images (from 158 patients) were
      reviewed by teleradiology. Teleradiology changed patient management in 36 cases
      (23.5%). Two (1.3%) of them were cases of pulmonary tuberculosis not previously
      suspected by clinical staff. In addition, the radiologist's review corrected the
      misdiagnosis of tuberculosis and averted inappropriate treatment in 16 patients
      (10.5%). LESSONS LEARNT: Teleradiology can improve tuberculosis diagnosis and
      case management, especially if criteria to identify the patients most suitable
      for referral are developed and the radiologist is conversant with local resources
      and health problems. Designating a clinical focal point for teleradiology ensures
      sustainability. Staff need time to adapt to a new teleradiology programme.

PMID- 22984315
TI  - Implementing early infant diagnosis of HIV infection at the primary care level:
      experiences and challenges in Malawi.
AB  - PROBLEM: Malawi's national guidelines recommend that infants exposed to the human
      immunodeficiency virus (HIV) be tested at 6 weeks of age. Rollout of services for
      early infant diagnosis has been limited and has resulted in the initiation of
      antiretroviral therapy (ART) in very few infants. APPROACH: An early infant
      diagnosis programme was launched. It included education of pregnant women on
      infant testing, community sensitization, free infant testing at 6 weeks of age,
      active tracing of HIV-positive infants and referral for treatment and care. LOCAL
      SETTING: The programme was established in two primary care facilities in
      Blantyre, Malawi. RELEVANT CHANGES: Of 1214 HIV-exposed infants, 71.6% presented
      for early diagnosis, and 14.5% of those who presented tested positive for HIV.
      Further testing of 103 of these 126 apparently HIV-positive infants confirmed
      infection in 88; the other 15 results were false positives. The initial
      polymerase chain reaction testing of dried blood spots had a positive predictive
      value (PPV) of 85.4%. Despite active tracing, only 87.3% (110/126) of the mothers
      of infants who initially tested positive were told their infants' test results.
      ART was initiated in 58% of the infants with confirmed HIV infection. LESSONS
      LEARNT: Early infant diagnosis of HIV infection at the primary care level in a
      resource-poor setting is challenging. Many children in the HIV diagnosis and
      treatment programme were lost to follow-up at various stages. Diagnostic tools
      with higher PPV and point-of-care capacity and better infrastructures for
      administering ART are needed to improve the management of HIV-exposed and HIV
      infected infants.

PMID- 22984317
TI  - Women, abortion and the new technical and policy guidance from WHO.

PMID- 22984318
TI  - Self-Reported Childhood Physical Abuse and Perpetration of Intimate Partner
      Violence: The Moderating Role of Psychopathic Traits.
AB  - Whereas considerable evidence links childhood physical abuse with later
      perpetration of intimate partner violence (IPV), research to identify moderators
      of this relationship will increase our understanding of which victims of
      childhood abuse are at risk for later IPV. The present study examined dimensions
      of psychopathy as moderators of the relationship between physical abuse in
      childhood and perpetration of IPV in a sample of criminal offenders. Results
      indicated that, among individuals with higher levels of impulsive-irresponsible
      (i.e., Lifestyle) traits of psychopathy, childhood physical abuse was associated
      with later perpetration of IPV. Findings have implications for the propensity
      toward IPV perpetration among individuals who have experienced childhood physical
      abuse.

PMID- 22984319
TI  - Elderly Asian and Hispanic Foreign- and Native-Born Living Arrangements:
      Accounting for Differences.
AB  - This study examines the relative importance of demographic, resource, and
      assimilation statuses in explaining the living arrangements of foreign- and
      native-born Asian and Hispanic elders from 11 origins in 2000 and accounting for
      why these groups have higher levels of extended living than native-born Whites.
      Drawing on the 2000 Public Use Microdata 5% Sample (PUMS) files and using
      logistic regression, the findings show that demographic characteristics are the
      major determinants of elderly extended living, followed by resource availability,
      assimilation, and group origin. Assimilation, on the other hand, is the major
      determinant of group differences between native White and Asian and Hispanic
      elders. While findings provide support for assimilation theory, the persistence
      of differentials across Asian and Hispanic groups after controlling for model
      covariates, and modest increases in extended living for most native-born Asian
      and Hispanic groups as well as native Whites in the 1990s underscores the
      enduring nature of ethnic diversity in living arrangements.

PMID- 22984320
TI  - Asymmetric forceps increase fighting success among males of similar size in the
      maritime earwig.
AB  - Extreme asymmetric morphologies are hypothesized to serve an adaptive function
      that counteracts sexual selection for symmetry. However direct tests of function
      for asymmetries are lacking, particularly in the context of animal weapons. The
      weapon of the maritime earwig, Anisolabis maritima, exhibits sizeable variation
      in the extent of directional asymmetry within and across body sizes, making it an
      ideal candidate for investigating the function of asymmetry. In this study, we
      characterized the extent of weapon asymmetry, characterized the manner in which
      asymmetric weapons are used in contests, staged dyadic contests between males of
      different size classes and analyzed the correlates of fighting success. In
      contests between large males, larger individuals won more fights and emerged as
      the dominant male. In contests between small males, however, weapon asymmetry was
      more influential in predicting overall fighting success than body size. This
      result reveals an advantage of asymmetric weaponry among males that are below the
      mean size in the population. A forceps manipulation experiment suggests that
      asymmetry may be an indirect, correlate of a morphologically independent factor
      that affects fighting ability.

PMID- 22984321
TI  - Examining Racial Disproportionality in Child Protective Services Case Decisions.
AB  - Using a national sample of 1,461 child protective services (CPS) investigations
      in the United States, we examine differences between black and white families
      with regard to caseworker ratings of risk and harm to the child, as well as the
      probability that a case is substantiated for maltreatment. We employ difference
      in-difference methods to identify whether gaps in outcomes for black and white
      families are equivalent when black and white CPS workers conduct the
      investigation, and Blinder-Oaxaca decomposition methods to identify the portion
      of the black-white difference in outcomes that is attributable to differences in
      case characteristics (risk factors) versus differences in associations between
      these characteristics and the outcomes by race (differential treatment). We find
      no differences in outcomes by child race after adjusting for case
      characteristics. At the same time, we find that relative to white caseworkers,
      black caseworkers are more likely to rate black children at subjectively higher
      risk of harm than white children and are also more likely to substantiate black
      families for maltreatment. The decomposition results suggest that-even after
      accounting for caseworker race-differences in outcomes for black and white
      children are primarily explained by differences in family and case circumstances
      rather than differential treatment. Thus, our analyses suggest that interventions
      addressing maltreatment-related risk factors that disproportionately affect black
      families may have greater utility for reducing racial disparities in CPS
      involvement than current emphases on cultural competence training.

PMID- 22984322
TI  - New Fathers? Residential Fathers' Time with Children in Four Countries.
AB  - We examine variation in employed fathers' time with children ages zero to 14,
      utilizing time use surveys from the United States (2003), Germany (2001), Norway
      (2000), and the United Kingdom (2000). We examine levels of father involvement
      and mechanisms associated involvement on both weekdays (N = 4,192) and weekends
      (N = 3,024). We find some evidence of "new fathers" on weekends in all countries.
      Fathers spend more time on interactive care and more time alone with children on
      weekends than on weekdays. Only Norwegian fathers, however, increase both their
      participation in and time spent on physical care. American and British fathers'
      time with children, however, is more responsive to partners' employment.

PMID- 22984323
TI  - On Spatial Processes and Asymptotic Inference under Near-Epoch Dependence.
AB  - The development of a general inferential theory for nonlinear models with cross
      sectionally or spatially dependent data has been hampered by a lack of
      appropriate limit theorems. To facilitate a general asymptotic inference theory
      relevant to economic applications, this paper first extends the notion of near
      epoch dependent (NED) processes used in the time series literature to random
      fields. The class of processes that is NED on, say, an alpha-mixing process, is
      shown to be closed under infinite transformations, and thus accommodates models
      with spatial dynamics. This would generally not be the case for the smaller class
      of alpha-mixing processes. The paper then derives a central limit theorem and law
      of large numbers for NED random fields. These limit theorems allow for fairly
      general forms of heterogeneity including asymptotically unbounded moments, and
      accommodate arrays of random fields on unevenly spaced lattices. The limit
      theorems are employed to establish consistency and asymptotic normality of GMM
      estimators. These results provide a basis for inference in a wide range of models
      with spatial dependence.

PMID- 22984324
TI  - Topological and Conformational Effects on Electron Transfer Dynamics in Porphyrin
      [60]Fullerene Interlocked Systems.
AB  - The effect of molecular topology, and conformation on the dynamics of
      photoinduced electron transfer (ET) processes has been studied in interlocked
      electron donor-acceptor systems, specifically rotaxanes with zinc(II)
      tetraphenylporphyrin (ZnP) electron donor and [60]fullerene (C(60)) as the
      electron acceptor. Formation or cleavage of coordinative bonds was used to induce
      major topological and conformational changes in the interlocked architecture. In
      the first approach, the tweezers-like structure created by the two ZnP stopper
      groups on the thread was used as a recognition site for complexation of 1,4
      diazabicyclo[2.2.2]octane (DABCO), which creates a bridge between the two ZnP
      moieties on the rotaxane, generating a catenane structure. The photoinduced
      processes in the DABCO-complexed (ZnP)(2)-[2]catenate-C(60) system were compared
      with those of the (ZnP)(2)-rotaxane-C(60) precursor and the previously reported
      ZnP-[2]catenate-C(60). Steady-state emission and transient absorption studies
      showed that a similar multistep ET pathway emerged for rotaxanes and catenanes
      upon photoexcitation at various wavelengths, ultimately resulting in a long-lived
      ZnP(*+)/C(60) (*-) charge separated radical pair state. However, the decay
      kinetics of the latter states clearly reflect the topological differences between
      the rotaxane, the catenate, and DABCO-complexed-catenate architectures. The
      lifetime of the long-distance ZnP(*+)-[Cu(I)phen(2)](+)-C(60) (*-) charge
      separated state is more than four times longer in 3 (1.03 us) than in 1 (0.24 us)
      and approaches that in catenate 2 (1.1 us). The results clearly showed that
      adoption of a catenane from a rotaxane topology inhibits the charge recombination
      process. In a second approach, the Cu(I) ion used as template to assemble the
      (ZnP)(2)-[Cu(I)phen(2)](+)-C(60) rotaxane was removed, and structural analysis
      suggested a major topographical change occurred, such that charge separation
      between the chromophores was no longer observed upon photoexcitation in nonpolar
      as well as polar solvents. Only ZnP and C(60) triplet excited states were
      observed upon laser excitation. These results highlighted the critical importance
      of the central Cu(I) ion for long range ET processes in these large interlocked
      electron donor-acceptor systems.

PMID- 22984325
TI  - Daily oscillation of glutathione redox cycle is dampened in the nutritional
      vitamin A deficiency.
AB  - Examples of hormonal phase-shifting of circadian gene expression began to emerge
      a few years ago. Vitamin A fulfills a hormonal function by binding of retinoic
      acid to its nuclear receptors, RARs and RXRs. We found retinoid- as well as clock
      responsive sites on regulatory regions of Glutathione reductase (GR) and
      Glutathione peroxidase (GPx) genes. Interestingly, we observed retinoid
      receptors, as well as GSH, GR and GPx, display daily oscillating patterns in the
      rat liver. We also found that feeding animals with a vitamin A-free diet,
      dampened daily rhythms of RARalpha and RXRbeta mRNA, GR expression and activity,
      GSH, BMAL1 protein levels and locomotor activity. Differently, day-night
      oscillations of RXRalpha, GPx mRNA levels and activity and PER1 protein levels,
      were phase-shifted in the liver of vitamin A-deficient rats. These observations
      would emphasize the importance of micronutrient vitamin A in the modulation of
      biological rhythms of GSH and cellular redox state in liver.

PMID- 22984326
TI  - Clinical characteristics of cataract patients with pseudoexfoliation syndrome at
      jimma university specialized hospital, South west ethiopia.
AB  - BACKGROUND: Pseudoexfoliation is the most common identifiable cause of secondary
      glaucoma and pseudoexfoliation patients have higher rates of intraoperative and
      postoperative complications of cataract surgery compared to those without the
      condition. Hence, the objective of this study was to assess the clinical
      characteristics of pseudoexfoliation syndrome among cataract patients examined at
      Jimma University Specialized Hospital, Southwest Ethiopia. METHODS: A cross
      sectional clinic based study was conducted from January-March 2009. A total of
      402 subjects with cataract were examined for the presence of pseudoexfoliation
      material, type of cataract, intraocular pressure, glaucoma and other factors. The
      presence of any exfoliation material on the iris, pupil and lens capsule was
      examined. Data were computed using SPSS version 16.0. RESULTS: Out of the 402
      patients examined, 144(35.82%) of them had presenile and senile cataract with
      pseudoexfoliation and out of these 144 cases, 48(33%) were unilateral and
      96(66.7%) were bilateral. Furthermore, 41(28.5%) cases had raised intraocular
      pressure, of which 2(4.9%) cases had chronic angle closure glaucoma and 39(95.1%)
      of the cases had open angle pseudoexfoliative glaucoma. There was also lens
      sublaxation in 10(6.9%) of the cases and dislocation in 6(4.2%) of the cases. The
      prevalence of PEX was higher (41%) in the age group of 70 years and above
      followed by 60-69 years (27.8%). CONCLUSION: A significant number of patients
      with PEX had poor zonular integrity and high IOP and/or glaucoma. Population
      based studies are recommended to assess its prevalence in the general population
      and its association with cataract and glaucoma.

PMID- 22984327
TI  - Postoperative Nosocomial Infections and Antimicrobial Resistance Pattern of
      Bacteria Isolates among Patients Admitted at Felege Hiwot Referral Hospital,
      Bahirdar, Ethiopia.
AB  - BACKGROUND: Nosocomial infection constitutes a major public health problem
      worldwide. Increasing antibiotic resistance of pathogens associated with
      nosocomial infections also becomes a major therapeutic challenge for physicians.
      Thus, the aim of this study was to identify post operative bacterial infections
      and determine their current antimicrobial resistance to commonly prescribed
      drugs. METHODS: A cross sectional study was conducted on patients under gone
      operation from October 2010 to January 2011 and followed for development of
      clinical signs and symptoms of surgical site and blood stream infection until the
      time of discharge. Structured questionnaire was used to collect socio demographic
      characteristics. Wound swab and venous blood samples were collected and processed
      for bacterial isolation and antimicrobial susceptibility testing following
      standard bacteriological techniques. RESULTS: Out of 294 patients who had clean
      and clean-contaminated operation, 10.9% were confirmed of bacterial nosocomial
      infections. The rate of nosocomial infections among clean and clean-contaminated
      operations was 3.3% and 12.8% respectively. Nosocomial surgical site and blood
      stream infection rate was 10.2% and 2.4% correspondingly. A total of 42 bacterial
      pathogens were identified of which S. aureus was the leading isolates accounting
      26.2% followed by E. coli and Coagulase negative Staphylococcus species each
      21.4%. Nearly 100% of Gram positive and 95.5% of Gram negative bacterial isolates
      showed resistance against two or more antimicrobial drugs. CONCLUSIONS: Multiple
      drug resistance of isolates to antimicrobials was alarmingly high so that any
      empirical prophylaxis and treatment needs careful selection of effective drugs.
      To minimize such infections, adherence of strict aseptic surgical procedures and
      proper management of wounds is required.

PMID- 22984328
TI  - Quality of Liver and Kidney Function Tests among Public Medical Laboratories in
      Western Region of Amhara National Regional State of Ethiopia.
AB  - BACKGROUND: Medical laboratories play essential roles in measurements of
      substances in body fluids for the purpose of diagnosis, treatment, prevention,
      and for greater understanding of the disease process. Thus, data generated from
      have to be reliable for which strict quality control, management and assurance
      are maintained. The aim of this study is to assess the accuracy and precision of
      clinical chemistry laboratories in western region of Amhara national regional
      state of Ethiopia in testing liver and kidney functions. METHODS: Eight
      laboratories in hospitals and a Regional Health Research Laboratory Center
      participated in this study from February to March, 2011. Each participant was
      requested to measure six specimens for six chemistry tests from two control
      samples. Three hundred twenty four test results to be reported from all
      participant laboratories, if all measurements can be made, were designed to be
      collected and statistically evaluated. RESULTS: None of the study subject
      laboratories could deliver all the six tests for estimation of both liver and
      renal functions simultaneously during the study period. Only 213 values from the
      expected 324 values were reported and about 65 % of the 213 values reported fell
      outside of the allowable limits of errors for the chemistry tests of the control
      specimen used. CONCLUSION: This study finding showed that there were lack of
      accuracy and precision in chemistry measurements. A regular survey on medical
      laboratories should be conducted questioning the accuracy and precision of their
      analyses in order to sustain improvements in the quality of services provided by
      participating laboratories for the benefit of patients. Laboratory Quality
      Management Systems appreciate the need for regular quality control and quality
      assessment schemes in medical laboratories.

PMID- 22984329
TI  - The sanitary conditions of food service establishments and food safety knowledge
      and practices of food handlers in bahir dar town.
AB  - BACKGROUND: Lack of basic infrastructure, poor knowledge of hygiene and practices
      in food service establishments can contribute to outbreaks of foodborne
      illnesses. The aims of this study were to investigate the food safety knowledge
      and practices of food handlers and to assess the sanitary conditions of food
      service establishments in Bahir Dar town. METHODS: A cross-sectional study was
      conducted in Bahir Dar in May 2011 and data were collected using questionnaire
      and observation checklist on employees' knowledge of food hygiene and their
      practices as well on sanitary conditions of the food service establishments
      RESULTS: The median age of the food handlers was 22 years and among the 455
      subjects 99 (21.8%) have had food hygiene training. Sixty six percent of the
      establishments had flush toilets whereas 5.9% of the establishment had no toilet.
      Only 149 (33.6%) of the establishments had a proper solid waste collection
      receptacle and there was statistically significant association between the
      sanitary conditions and license status of the establishments (p=0.01). Most of
      all, knowledge gap in food hygiene and handling practice was observed. In
      addition, there was statistically significant difference between trained
      (professional) handlers and non-trained handlers with regard to food hygiene
      practices (p<0.05). While more than 50% of the handlers prepare meals ahead of
      the peak selling time, more than 50% of the left over was poorly managed.
      CONCLUSION: This study revealed poor sanitary conditions and poor food hygiene
      practices of handlers. Educational programs targeted at improving the attitude of
      food handlers and licensing and regular inspections have been recommended.

PMID- 22984330
TI  - HIV Sero-Prevalence Trend among Blood Donors in Jimma University Specialized
      Hospital, Southwest Ethiopia.
AB  - BACKGROUND: HIV/AIDS epidemics continue unchecked in African countries at all
      level of society bearing the heaviest burden of the scourge. Different researches
      have been done to see the progress of disease from time to time However,
      information that shows the trend of HIV among the healthy population over a
      period of time in Ethiopia is very limited. METHODS: A descriptive retrospective
      cross-sectional study was carried out to see the trend of HIV Sero-positivity and
      associated socio-demographic factors. The data was retrieved from records of
      people who donated blood during the period of January 2007 to December 2010, at
      Jimma University Specialized Hospital (JUSH). Data on socio-demographic variables
      and serologic status of the subjects were abstracted from their records using
      structured format. Then the data were cleaned, edited and entered into computer
      and analyzed by Microsoft Excel sheet. Then Chi-Square (X(2)) Statistical test
      was used for testing associations and P value less or equal to five percent (P <=
      0.05) was considered significant. RESULTS: A total of 3788 subjects had donated
      blood from 2007 to 2010 of which 3034 (80.1 %) were males. Thirty nine (1%) of
      the donors were positive for HIV upon screening by Enzyme Linked Immuno Sorbent
      Assay (ELISA) method. The prevalence of HIV infection was 1.2% for males and 0.5%
      for females. The age specific prevalence was highest in the age group 30-39 years
      (2.2%) followed by 40 - 49 (1.4%). HIV sero-prevalence was higher among rural
      dwellers (1.4%) than urban (0.8%); drivers and their assistants (2.8%), and daily
      laborers (2.6%) had higher prevalence. Similarly, those who donated blood for
      replacement purpose had higher sero-prevalence (1.5%) as compared to those on
      voluntary basis (0.3%). CONCLUSION: There is decreasing trend of sero-positivity
      over the years, with higher prevalence among sexually active age groups and rural
      dwellers.

PMID- 22984331
TI  - Outcome of teenage pregnancy in the niger delta of Nigeria.
AB  - BACKGROUND: Young maternal age at delivery has been proposed as risk factor for
      adverse pregnancy outcome, it occurs in all races, faiths, socioeconomic
      statuses, and regions. Teenage pregnancy can have serious physical consequences
      and teenage mothers are likely to be unmarried, poor and remain uneducated. The
      objective of the study was to evaluate risk factors associated with teenage
      pregnancy and compare the obstetric and fetal outcome to older parturient.
      METHODS: This is a retrospective study performed over a period of 4 Years
      (January 1, 2007 to December 31, 2010) in Niger Delta University Teaching
      Hospital Bayelsa State, Nigeria where data was retrieved from the hospital
      records. All teenage mothers (aged 13-19) who had delivery within the period were
      compared with 180 randomly selected deliveries in the older age group (20-32
      years) over the same period. Variables of interest were the demographic
      characteristics of the women, their obstetric complications and the outcome.
      RESULTS: There were a total of 1341 deliveries during the study period, out which
      83(6.2%) were teenagers. Teenage mothers were significantly more likely to be
      unbooked, (p = 0.000) Unmarried, (chi=26.2; p = 0.000) had significantly more
      preterm labor, (P=0.000) and Caesarean sections (P= 0.014). However, there was no
      difference in both the perinatal and maternal mortality rates between the two
      groups. CONCLUSION: Teenage pregnancy in the Niger Delta is concentrated among
      women with less formal education, who are unemployed, unmarried and with
      inadequate antenatal care and obstetric risks for poor pregnancy outcome. The
      provision an appropriate contraceptive method and to look with priority after any
      pregnancy occurring among this age group cannot be overemphasized.

PMID- 22984332
TI  - The child sexual abuse epidemic in addis ababa: some reflections on reported
      incidents, psychosocial consequences and implications.
AB  - BACKGROUND: Though child sexual abuse is a universal phenomenon, only reported
      cases of the incidence are common source of information to get insight on how to
      understand the problem. Besides, investigating complaints presented by victims
      themselves would be a stepping stone for designing prevention and rehabilitation
      programs. The objective of this study was to identify the nature of sexual
      incidence and experience victims face. METHODS: The research was conducted by
      collecting reported child sexual abuse cases from Child Protection Units of Addis
      Ababa Police Commission and three selected non-governmental organizations working
      for the welfare of sexually abused children in Addis Ababa. 64 selected samples
      of victim children were included from the three organizations. They completed a
      semi-structured questionnaire and data were analyzed. RESULTS: Of the total
      reported crime cases committed against children (between July 2005 and December
      2006), 23% of them were child sexual victimization. On average, 21 children were
      reported to be sexually abused each month where majority of the sexual abuse
      incidence were committed against female children in their own home by someone
      they closely know. The psychological trauma and physical complaints presented by
      victims include symptoms of anxiety and depression. CONCLUSION: It was found out
      that child sexual abuse cases presented to the legal office was not properly
      managed. Female children appear to be more prone to sexual abuse than their male
      counterparts. By virtue of their nature, many children are at risk of sexual
      victimization by people they truest. Based on the findings, several implications
      are made, which includes the importance of nation-wide study to formulate a
      comprehensive policy guideline for protection and criminalization of child sexual
      abuse in Ethiopia.

PMID- 22984334
TI  - Is it early to talk about unethical publication practices?

PMID- 22984333
TI  - Smear Posetive Pulmonary Tuberculosis (PTB) Prevalence Amongst Patients at Agaro
      Teaching Health Center, South West Ethiopia.
AB  - BACKGROUND: World Health organization (WHO) declared tuberculosis as a global
      emergency because it poses a serious public health threat in different countries
      especially, in Africa. According to WHO report of 2007, Directly Observed
      Treatment Short course (DOTS) coverage in Ethiopia reached 95 percent of the
      population; despite this fact the trend of tuberculosis in most of the districts
      of Ethiopia is not known. Hence, this study has revealed the trend and determined
      the overall prevalence of smear positive pulmonary tuberculosis in five years
      (2005/6-2009/10) in Agaro teaching health center, south west Ethiopia. METHODS: A
      retrospective study based on record review was conducted at Agaro Teaching Health
      center on sputum examination record of patient's from 2005/6-2009/10(five years).
      Socio demographic data and sputum laboratory results were collected using pre
      designed questionnaire and the data was entered into a computer using SPSS
      version 16 for windows. Finally, cross tab analysis and Chi-square was calculated
      at P-value less than 0.05 to check possible association between socio-demographic
      variables and smear positivity. RESULTS: The overall five years prevalence of
      smear positive pulmonary tuberculosis was found out to be 10.9%. On the other
      hand, the percentage of smear positive pulmonary tuberculosis cases showed
      gradual decrease from 19.5% in 2005/6 to 5.8% cases in 2009/10. CONCLUSION:
      Tuberculosis is still the major problem of Agaro health center catchment area
      even though there is a decrease in trend from year to year. Hence, the respective
      health bureau and other stake holders should still need to strengthen their
      effort to control it.

PMID- 22984335
TI  - Toward open behavioral science.

PMID- 22984336
TI  - Electronic Play, Study, Communication, and Adolescent Achievement, 2003 to 2008.
AB  - Adolescents' time spent messaging, exploring websites, and studying on the
      computer increased between 2003 and 2008. Using data from the Panel Study of
      Income Dynamics Child Development Supplement, this study examines how such
      changes have influenced individual achievement and behavior from childhood to
      adolescence. Greater communications and Internet web time proved detrimental to
      vocabulary and reading whereas the increased use of computer games was associated
      with increased reading and problem-solving scores, particularly for girls and
      minority children. Increased use of the computer for studying was associated with
      increased test scores for girls but not boys. The consequences are more benign
      than many feared. Groups that have traditionally used the computer less (girls,
      minority children) appear to benefit from greater use.

PMID- 22984337
TI  - The Significance of Strategic Community Engagement in Recruiting African American
      Youth & Families for Clinical Research.
AB  - We present baseline data and describe the utility of a community engaged,
      culturally relevant approach to recruiting African American youth and families
      for phase I of The AAKOMA Project. The AAKOMA Project is a two phase treatment
      development study to improve mental health service use among depressed African
      American youth. We completed capacity building activities using a community
      engaged framework and Community Based Participatory Research (CBPR) methods.
      Replicating the (Alvarez et al. in West J Nurs Res 28:541-560, 2006) model of
      systematic community out-reach enhanced our ability to effectively recruit
      partners and evaluate outreach efforts as demonstrated by our Recruitment Success
      Factor (RSF-i.e. 'an adjusted ratio of eligible participant yield to contacts
      made'). Using the chi-square goodness-of-fit statistic; we compared the RSFs of
      the various modes of participant study entry to determine which was most
      effective. Our target enrollment was 56 persons. We recruited 130 and enrolled
      57. Our baseline data is drawn from a gender balanced and socioeconomically
      diverse sample who participated in youth focus groups and individual interviews
      and adult focus groups. We identified 3 study participant referral modes (self
      referral, provider referral and participant-to-participant referral) with
      multiple sources per mode and an overall RSF of 0.41. Study findings support the
      effectiveness of assiduous and systematic community interaction, reflective
      review of recruitment efforts and the importance of disseminating information on
      strategic recruitment processes for engaging diverse populations in clinical
      research.

PMID- 22984338
TI  - Guaranteeing Convergence of Iterative Skewed Voting Algorithms for Image
      Segmentation.
AB  - In this paper we provide rigorous proof for the convergence of an iterative
      voting-based image segmentation algorithm called Active Masks. Active Masks (AM)
      was proposed to solve the challenging task of delineating punctate patterns of
      cells from fluorescence microscope images. Each iteration of AM consists of a
      linear convolution composed with a nonlinear thresholding; what makes this
      process special in our case is the presence of additive terms whose role is to
      "skew" the voting when prior information is available. In real-world
      implementation, the AM algorithm always converges to a fixed point. We study the
      behavior of AM rigorously and present a proof of this convergence. The key idea
      is to formulate AM as a generalized (parallel) majority cellular automaton,
      adapting proof techniques from discrete dynamical systems.

PMID- 22984339
TI  - Perceptual and Articulatory Changes in Speech Production Following PROMPT
      Treatment.
AB  - PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets) is a treatment
      approach that is widely used to improve sound production in children with speech
      impairments. This approach uses tactile cues to support and shape movements of
      the oral articulators in order to improve the production of individual sounds,
      syllables, words, and eventually connected speech. The underlying assumption is
      that tactile cuing will facilitate changes in articulator movements. This
      investigation examined articulator movement as well as the accuracy of speech
      production, before, during, and after a period of PROMPT treatment in a child
      with severe articulation impairment. A typically developing child was followed
      longitudinally as a control. The following research questions were addressed: (1)
      Does speech sound accuracy improve over an eight-week course of PROMPT treatment?
      (2) Does articulator movement (duration, displacement, velocity) change over an
      eight-week course of PROMPT treatment? The results revealed increased
      articulation accuracy and decreased movement duration, displacement, and velocity
      over the course of PROMPT treatment in the child with the articulation
      impairment. By the last treatment session, kinematic findings were most similar
      to those seen in the control. These results suggest that PROMPT facilitated
      changes in articulatory control in a single participant.

PMID- 22984340
TI  - CROSS-CURRENTS BETWEEN BIOLOGY AND MATHEMATICS: THE CODIMENSION OF PSEUDO-PLATEAU
      BURSTING.
AB  - A great deal of work has gone into classifying bursting oscillations, periodic
      alternations of spiking and quiescence modeled by fast-slow systems. In such
      systems, one or more slow variables carry the fast variables through a sequence
      of bifurcations that mediate transitions between oscillations and steady states.
      A rigorous classification approach is to characterize the bifurcations found in
      the neighborhood of a singularity; a measure of the complexity of the bursting
      oscillation is then given by the smallest codimension of the singularities near
      which it occurs. Fold/homoclinic bursting, along with most other burst types of
      interest, has been shown to occur near a singularity of codimension three by
      examining bifurcations of a cubic Lienard system; hence, these types of bursting
      have at most codimension three. Modeling and biological considerations suggest
      that fold/homoclinic bursting should be found near fold/subHopf bursting, a more
      recently identified burst type whose codimension has not been determined yet. One
      would expect that fold/subHopf bursting has the same codimension as
      fold/homoclinic bursting, because models of these two burst types have very
      similar underlying bifurcation diagrams. However, no codimension-three
      singularity is known that supports fold/subHopf bursting, which indicates that it
      may have codimension four. We identify a three-dimensional slice in a partial
      unfolding of a doubly-degenerate Bodganov-Takens point, and show that this
      codimension-four singularity gives rise to almost all known types of bursting.

PMID- 22984341
TI  - Novel Applications of Rapid Prototyping in Gamma-ray and X-ray Imaging.
AB  - Advances in 3D rapid-prototyping printers, 3D modeling software, and casting
      techniques allow for the fabrication of cost-effective, custom components in
      gamma-ray and x-ray imaging systems. Applications extend to new fabrication
      methods for custom collimators, pinholes, calibration and resolution phantoms,
      mounting and shielding components, and imaging apertures. Details of the
      fabrication process for these components are presented, specifically the 3D
      printing process, cold casting with a tungsten epoxy, and lost-wax casting in
      platinum.

PMID- 22984342
TI  - VGLUT2 mRNA and protein expression in the visual thalamus and midbrain of
      prosimian galagos (Otolemur garnetti).
AB  - Vesicular glutamate transporters (VGLUTs) control the storage and presynaptic
      release of glutamate in the central nervous system, and are involved in the
      majority of glutamatergic transmission in the brain. Two VGLUT isoforms, VGLUT1
      and VGLUT2, are known to characterize complementary distributions of
      glutamatergic neurons in the rodent brain, which suggests that they are each
      responsible for unique circuits of excitatory transmission. In rodents, VGLUT2 is
      primarily utilized in thalamocortical circuits, and is strongly expressed in the
      primary sensory nuclei, including all areas of the visual thalamus. The
      distribution of VGLUT2 in the visual thalamus and midbrain has yet to be
      characterized in primate species. Thus, the present study describes the
      expression of VGLUT2 mRNA and protein across the visual thalamus and superior
      colliculus of prosimian galagos to provide a better understanding of
      glutamatergic transmission in the primate brain. VGLUT2 is strongly expressed in
      all six layers of the dorsal lateral geniculate nucleus, and much less so in the
      intralaminar zones, which correspond to retinal and superior collicular inputs,
      respectively. The parvocellular and magnocellular layers expressed VGLUT2 mRNA
      more densely than the koniocellular layers. A patchy distribution of VGLUT2
      positive terminals in the pulvinar complex possibly reflects inputs from the
      superior colliculus. The upper superficial granular layers of the superior
      colliculus, with inputs from the retina, most densely expressed VGLUT2 protein,
      while the lower superficial granular layers, with projections to the pulvinar,
      most densely expressed VGLUT2 mRNA. The results are consistent with the
      conclusion that retinal and superior colliculus projections to the thalamus
      depend highly on the VGLUT2 transporter, as do cortical projections from the
      magnocellular and parvocellular layers of the lateral geniculate nucleus and
      neurons of the pulvinar complex.

PMID- 22984343
TI  - The Association between Romantic Relationships and Delinquency in Adolescence and
      Young Adulthood.
AB  - This study examined the association between romantic relationships and
      delinquency in adolescence and young adulthood. Using a large, longitudinal, and
      nationally representative sample, results from negative binomial regressions
      showed a positive association between romantic involvement and delinquency in
      adolescence. Further, the cumulative number of romantic relationships from
      adolescence to young adulthood was positively related to delinquency in young
      adulthood even controlling for earlier delinquency in adolescence. These analyses
      also controlled for the effects of participant gender, age at initial assessment,
      puberty, race/ethnicity, and other demographic characteristics (e.g., family
      structure and parents' education). Findings are discussed in terms of their
      implications for understanding the role of romantic relationships in the
      development of young people and for stimulating future research questions.

PMID- 22984344
TI  - Religious Doubt, Financial Strain, and Depressive Symptoms Among Older Mexican
      Americans.
AB  - PURPOSE: A number of studies suggest that positive aspects of religion (e.g.,
      social support from fellow church members) help older people cope more
      effectively with stress. However, researchers have known for some time that there
      are negative as well as positive facets of religion. This suggests that instead
      of enhancing coping efforts, religion may also exacerbate the effects of stress.
      The purpose of this study was to see if one negative aspect of religion (i.e.,
      religious doubt) exacerbates the effects of financial strain on depressive
      symptoms among older Mexican Americans.  METHODS: A nationwide survey of 1,005
      older Mexican Americans was conducted. Measures of religious doubt, financial
      strain, and depressive symptoms were administered.  RESULTS: The findings suggest
      that the effects of financial strain on depressive symptoms are stronger for
      older Mexican Americans who have more doubts about religion.  CONCLUSIONS: This
      study explores aspects of religion that have received relatively little attention
      in the literature (i.e., religious doubt). Moreover, the data were provided by
      members of an ethnic group that have been largely overlooked by researchers who
      study religion (i.e., older Mexican Americans). Taken together, these study
      attributes help provide greater balance in the literature on religion and mental
      health in late life.

PMID- 22984345
TI  - Maternal mortality in South Africa: An update from the 2007 Community Survey.
AB  - The 2007 Community Survey conducted in South Africa included questions on
      maternal deaths in the previous 12 months (pregnancy-related deaths). The
      Maternal Mortality Ratio (MMR) was estimated at 700 per 100,000 live births, some
      30% more than at the 2001 census. This high level occurred despite a low
      proportion of maternal deaths (4.3%) among deaths of women aged 15-49 years,
      which was even lower than the proportion of time spent in the maternal risk
      period (7.6%). The high level of MMR was due to the astonishingly high level of
      adult mortality, which increased by 46% since 2001. The main reasons for these
      excessive levels were HIV/AIDS and external causes of death (accidents and
      violence). Differentials in MMR were very marked, and similar to those found in
      2001 with respect to urban residence, race, province, education, income, and
      wealth. Provincial levels of MMR correlated primarily with HIV/AIDS prevalence.
      Maternal mortality defined as 'pregnancy-related death' appears no longer as a
      proper indicator of 'safe motherhood' in this situation.

PMID- 22984346
TI  - Frequency of Premature Infant Engagement and Disengagement Behaviors During Two
      Maternally Administered Interventions.
AB  - Although sensitive maternal behaviors improve later quality of mother-infant
      interaction and subsequently infant development, little is known regarding how an
      intervention might promote early premature infant social interactive behavior.
      This study compared the frequency of premature infant engagement and
      disengagement behaviors during two maternally administered interventions, the
      multi-sensory auditory, tactile, visual and vestibular intervention (ATVV) and
      kangaroo care (KC) for 26 infants between 31 and 46 weeks PMA. The ATVV
      intervention elicited more disengagement (M = 24 vs. 12, p = .0003), trended
      toward more engagement (M = 21 vs. 15.7, p = .06) and more potent engagement (M =
      24 vs. 12, p = .0003), subtle disengagement (M = 25 vs. 11.9, p < .0001), and
      potent disengagement (M = 22.9 vs. 14, p = . 006) behaviors than did KC. The ATVV
      intervention may be an intervention to promote the infant's learning how to
      regulate engagement and disengagement behaviors.

PMID- 22984347
TI  - Does Wartime Captivity Affect Late-life Mental Health? A Study of Vietnam-era
      Repatriated Prisoners of War.
AB  - Our earlier study of U.S. prisoners of war in Vietnam (King et al., 2011)
      examined personal and military demographics and aspects of the stressful
      experience of wartime imprisonment as they related to psychological well-being
      shortly after homecoming in 1973. Research with repatriated prisoners of war
      (RPWs) from other military eras suggests that the severity of captivity stressors
      might predict long-term distress. However, the extent to which effects of the
      captivity experience persisted for Vietnam-era RPWs is unknown. The present study
      extended our previous analyses by examining the associations of demographic
      factors, captivity stressors, and repatriation mental health with subsequent
      symptoms of posttraumatic stress disorder (PTSD), anxiety, and depressive
      symptoms (measured nearly 30 years later) in a sample of 292 Vietnam-era RPWs.
      Results indicated that although most of the men in our sample were within normal
      limits on anxiety and depressive symptoms, a substantial minority reported
      experiencing clinically significant levels. Levels of PTSD symptoms were
      generally low, with only a modest proportion demonstrating elevations. Multiple
      regression analyses showed that age at capture and posttraumatic stress symptoms
      at repatriation predicted all three long-term mental health outcomes. In
      addition, physical torture predicted long-term PTSD symptoms. Findings highlight
      the potential long-term effects of wartime captivity, and also suggest that most
      Vietnam-era RPWs demonstrate remarkable resilience to extraordinarily stressful
      life experiences.

PMID- 22984348
TI  - Women Vietnam Veterans: Do PTSD Symptoms Mediate Effects of Warzone Service on
      Health?
AB  - We assessed the impact of warzone stress on the physical and mental health
      functioning and well-being of 975 female nurse veterans who had been deployed to
      Vietnam, and examined whether PTSD symptoms at the time of the survey mediated
      these relations. A questionnaire was mailed to the Women's Vietnam Memorial
      Project members, approximately 25 - 30 years after their wartime service. We
      examined current physical and mental health functioning in relation to several
      measures of warzone stress and PTSD symptoms, adjusting for age, length of
      military service, and current physical health problems. Using regression models,
      we evaluated whether current PTSD symptoms mediated the effects of warzone stress
      on mental and physical health. Findings suggested that PTSD symptoms did mediate
      the relationship between warzone stress and mental, but not physical, health
      functioning in later life. These findings suggest that among women nurses
      deployed to Vietnam, the effects of warzone stress many years earlier on current
      functioning and well-being are both direct and indirect, mediated by PTSD
      symptoms. The legacy of wartime deployment remains, although muted in its
      expression, in military nurses nearly 30 years after their return.

PMID- 22984351
TI  - ESTIMATION OF DIRECTIONAL BRAIN ANISOTROPY FROM EEG SIGNALS USING THE MELLIN
      TRANSFORM AND IMPLICATIONS FOR SOURCE LOCALIZATION.
AB  - This paper presents a novel approach for the estimation of frequency-specific EEG
      scale modulations by the directional anisotropy of the brain, using the Mellin
      transform [1, 2, 3]. In the case of epileptic sources, the activity recorded by
      routine scalp EEG includes contributions not only from a seizure's primary
      propagation path but also from secondary paths and unrelated to the seizure
      activity. In addition, the anisotropy of the brain directionally modulates the
      seizure-related signal component. We estimated patient-specific direction
      specific, frequency-locked scale shifts. During the ictal interval, these shifts
      occurred at frequencies >=50 Hz. We further estimated the effect of scale
      modulations on time-delay estimation. Larger time-delays were estimated from EEGs
      that had been corrected by a scale factor prior to this estimation. Thus,
      corrections for non-linear scaling of EEGs may ultimately improve time-delay
      estimation for source localization, particularly in cases of seizures rapidly
      propagating to large areas of the brain.

PMID- 22984350
TI  - 3D-SIM super resolution microscopy reveals a bead-like arrangement for FtsZ and
      the division machinery: implications for triggering cytokinesis.
AB  - FtsZ is a tubulin-like GTPase that is the major cytoskeletal protein in bacterial
      cell division. It polymerizes into a ring, called the Z ring, at the division
      site and acts as a scaffold to recruit other division proteins to this site as
      well as providing a contractile force for cytokinesis. To understand how FtsZ
      performs these functions, the in vivo architecture of the Z ring needs to be
      established, as well as how this structure constricts to enable cytokinesis.
      Conventional wide-field fluorescence microscopy depicts the Z ring as a
      continuous structure of uniform density. Here we use a form of super resolution
      microscopy, known as 3D-structured illumination microscopy (3D-SIM), to examine
      the architecture of the Z ring in cells of two Gram-positive organisms that have
      different cell shapes: the rod-shaped Bacillus subtilis and the coccoid
      Staphylococcus aureus. We show that in both organisms the Z ring is composed of a
      heterogeneous distribution of FtsZ. In addition, gaps of fluorescence were
      evident, which suggest that it is a discontinuous structure. Time-lapse studies
      using an advanced form of fast live 3D-SIM (Blaze) support a model of FtsZ
      localization within the Z ring that is dynamic and remains distributed in a
      heterogeneous manner. However, FtsZ dynamics alone do not trigger the
      constriction of the Z ring to allow cytokinesis. Lastly, we visualize other
      components of the divisome and show that they also adopt a bead-like localization
      pattern at the future division site. Our data lead us to propose that FtsZ guides
      the divisome to adopt a similar localization pattern to ensure Z ring
      constriction only proceeds following the assembly of a mature divisome.

PMID- 22984349
TI  - Revisiting an old riddle: what determines genetic diversity levels within
      species?
AB  - Understanding why some species have more genetic diversity than others is central
      to the study of ecology and evolution, and carries potentially important
      implications for conservation biology. Yet not only does this question remain
      unresolved, it has largely fallen into disregard. With the rapid decrease in
      sequencing costs, we argue that it is time to revive it.

PMID- 22984352
TI  - DRINKING PATTERNS AND DSM-IV ALCOHOL USE DISORDERS' CRITERIA IN ARGENTINEAN
      EMERGENCY DEPARTMENT PATIENTS.
AB  - BACKGROUND: Previous studies have shown cultural variations in normative drinking
      and furthermore, in the quantity and frequency of drinking related to alcohol use
      disorders.  AIM: The main goal of this study is to characterize alcohol drinking
      patterns in Argentinean Emergency Department patients, and secondly, to explore
      the association between those drinking patterns and DSM-IV alcohol use disorders.
      METHOD: Data were collected from a probability sample of patients admitted to
      the Emergency Department of a large public hospital in Mar del Plata, Argentina.
      Data analyzed here pertain to those who reported consuming at least one drink
      during the last twelve months (n=529). A factor analysis of multiple
      correspondences and a hierarchic classification were performed. For the factor
      analysis, usual quantity and frequency of drinking (for the last 12 months) were
      considered active variables; number of DSM-IV dependence criteria met, positive
      or negative diagnostic status for abuse, positive or negative diagnostic status
      for dependence (both for the last 12 months), and socio-demographic
      characteristics (age, gender and economic level) were considered illustrative
      variables.  RESULTS: The first five factorial axes were retained, accounting for
      88% of the total variance. Hierarchic classification resulted in six distinctive
      classes of drinking patterns. Two patterns were associated with a positive
      diagnosis of abuse and dependence, respectively. One, drinking between 4 and 6
      drinks per occasion mostly on a weekly basis, was associated with a diagnosis of
      abuse; this pattern was also associated with meeting one or two dependence
      criteria (dependence orphans). The other, drinking 7 or more drinks per occasion,
      was associated with a diagnosis of dependence, and also with a diagnostic orphan
      condition. This class, composed primarily of males, was not characterized by any
      particular frequency of drinking. The other four drinking patterns were not
      associated with a positive diagnosis of an alcohol use disorder. Two of them were
      characterized by drinking low quantities with a low frequency (either monthly or
      yearly). Participants in both of these classes tended to be female. The other two
      patterns were characterized by drinking less than 3 drinks per occasion, either
      daily or weekly: the former associated with being older than 35 years, and the
      later with no distinctive socio-demographic characteristics.  CONCLUSIONS:
      Results demonstrated six distinct drinking patterns, two of them related to a
      positive diagnosis of an alcohol use disorder. Our findings support previous
      research indicating that dependence orphans share some characteristics with abuse
      and dependence cases. Given the lack of similar studies in the region, these
      findings, although descriptive, enrich the knowledge of alcohol use disorders in
      the regional context. Furthermore, they may contribute to the development of
      local drinking guidelines and prevention strategies.

PMID- 22984353
TI  - A systematic review and meta-analysis of utility-based quality of life in chronic
      kidney disease treatments.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a common and costly condition to
      treat. Economic evaluations of health care often incorporate patient preferences
      for health outcomes using utilities. The objective of this study was to determine
      pooled utility-based quality of life (the numerical value attached to the
      strength of an individual's preference for a specific health outcome) by CKD
      treatment modality. METHODS AND FINDINGS: We conducted a systematic review, meta
      analysis, and meta-regression of peer-reviewed published articles and of PhD
      dissertations published through 1 December 2010 that reported utility-based
      quality of life (utility) for adults with late-stage CKD. Studies reporting
      utilities by proxy (e.g., reported by a patient's doctor or family member) were
      excluded. In total, 190 studies reporting 326 utilities from over 56,000 patients
      were analysed. There were 25 utilities from pre-treatment CKD patients, 226 from
      dialysis patients (haemodialysis, n = 163; peritoneal dialysis, n = 44), 66 from
      kidney transplant patients, and three from patients treated with non-dialytic
      conservative care. Using time tradeoff as a referent instrument, kidney
      transplant recipients had a mean utility of 0.82 (95% CI: 0.74, 0.90). The mean
      utility was comparable in pre-treatment CKD patients (difference  =  -0.02; 95%
      CI: -0.09, 0.04), 0.11 lower in dialysis patients (95% CI: -0.15, -0.08), and 0.2
      lower in conservative care patients (95% CI: -0.38, -0.01). Patients treated with
      automated peritoneal dialysis had a significantly higher mean utility (0.80) than
      those on continuous ambulatory peritoneal dialysis (0.72; p = 0.02). The mean
      utility of transplant patients increased over time, from 0.66 in the 1980s to
      0.85 in the 2000s, an increase of 0.19 (95% CI: 0.11, 0.26). Utility varied by
      elicitation instrument, with standard gamble producing the highest estimates, and
      the SF-6D by Brazier et al., University of Sheffield, producing the lowest
      estimates. The main limitations of this study were that treatment assignments
      were not random, that only transplant had longitudinal data available, and that
      we calculated EuroQol Group EQ-5D scores from SF-36 and SF-12 health survey data,
      and therefore the algorithms may not reflect EQ-5D scores measured directly.
      CONCLUSIONS: For patients with late-stage CKD, treatment with dialysis is
      associated with a significant decrement in quality of life compared to treatment
      with kidney transplantation. These findings provide evidence-based utility
      estimates to inform economic evaluations of kidney therapies, useful for policy
      makers and in individual treatment discussions with CKD patients.

PMID- 22984354
TI  - Misrepresentation of randomized controlled trials in press releases and news
      coverage: a cohort study.
AB  - BACKGROUND: Previous studies indicate that in published reports, trial results
      can be distorted by the use of "spin" (specific reporting strategies, intentional
      or unintentional, emphasizing the beneficial effect of the experimental
      treatment). We aimed to (1) evaluate the presence of "spin" in press releases and
      associated media coverage; and (2) evaluate whether findings of randomized
      controlled trials (RCTs) based on press releases and media coverage are
      misinterpreted. METHODS AND FINDINGS: We systematically searched for all press
      releases indexed in the EurekAlert! database between December 2009 and March
      2010. Of the 498 press releases retrieved and screened, we included press
      releases for all two-arm, parallel-group RCTs (n = 70). We obtained a copy of the
      scientific article to which the press release related and we systematically
      searched for related news items using Lexis Nexis. "Spin," defined as specific
      reporting strategies (intentional or unintentional) emphasizing the beneficial
      effect of the experimental treatment, was identified in 28 (40%) scientific
      article abstract conclusions and in 33 (47%) press releases. From bivariate and
      multivariable analysis assessing the journal type, funding source, sample size,
      type of treatment (drug or other), results of the primary outcomes (all
      nonstatistically significant versus other), author of the press release, and the
      presence of "spin" in the abstract conclusion, the only factor associated, with
      "spin" in the press release was "spin" in the article abstract conclusions
      (relative risk [RR] 5.6, [95% CI 2.8-11.1], p < 0.001). Findings of RCTs based on
      press releases were overestimated for 19 (27%) reports. News items were
      identified for 41 RCTs; 21 (51%) were reported with "spin," mainly the same type
      of "spin" as those identified in the press release and article abstract
      conclusion. Findings of RCTs based on the news item was overestimated for ten
      (24%) reports. CONCLUSION: "Spin" was identified in about half of press releases
      and media coverage. In multivariable analysis, the main factor associated with
      "spin" in press releases was the presence of "spin" in the article abstract
      conclusion.

PMID- 22984355
TI  - External financial aid to blood transfusion services in sub-Saharan Africa: a
      need for reflection.
AB  - Jean-Pierre Allain and colleagues argue that, while unintended, the foreign aid
      provided for blood transfusion services in sub-Saharan Africa has resulted in
      serious negative outcomes, which requires reflection and rethinking.

PMID- 22984356
TI  - Routine Access to Millisecond Time Scale Events with Accelerated Molecular
      Dynamics.
AB  - In this work, we critically assess the ability of the all-atom enhanced sampling
      method accelerated molecular dynamics (aMD) to investigate conformational changes
      in proteins that typically occur on the millisecond time scale. We combine aMD
      with the inherent power of graphics processor units (GPUs) and apply the
      implementation to the bovine pancreatic trypsin inhibitor (BPTI). A 500 ns aMD
      simulation is compared to a previous millisecond unbiased brute force MD
      simulation carried out on BPTI, showing that the same conformational space is
      sampled by both approaches. To our knowledge, this represents the first
      implementation of aMD on GPUs and also the longest aMD simulation of a
      biomolecule run to date. Our implementation is available to the community in the
      latest release of the Amber software suite (v12), providing routine access to
      millisecond events sampled from dynamics simulations using off the shelf
      hardware.

PMID- 22984360
TI  - Alcohol Policy Comprehension, Compliance and Consequences Among Young Adult
      Restaurant Workers.
AB  - This study explores relationships between young adult restaurant employees'
      understanding and compliance with workplace alcohol control policies and
      consequences of alcohol policy violation. A mixed method analysis of 67 semi
      structured interviews and 1,294 telephone surveys from restaurant chain employees
      found that alcohol policy details confused roughly a third of employees. Among
      current drinkers (n=1,093), multivariable linear regression analysis found that
      frequency of alcohol policy violation was positively associated with frequency of
      experiencing problems at work; perceived supervisor enforcement of alcohol policy
      was negatively associated with this outcome. Implications for preventing
      workplace alcohol-related problems include streamlining confusing alcohol policy
      guidelines.

PMID- 22984361
TI  - Evaluating a New Risk Marker's Predictive Contribution in Survival Models.
AB  - Although the area under the receiver operating characteristic (ROC) curve (AUC)
      is the most popular measure of the performance of prediction models, it has
      limitations, especially when it is used to evaluate the added discrimination of a
      new risk marker in an existing risk model. Pencina et al. (2008) proposed two
      indices, the net reclassification improvement (NRI) and integrated discrimination
      improvement (IDI), to supplement the improvement in the AUC (IAUC). Their NRI and
      IDI are based on binary outcomes in case-control settings, which do not involve
      time-to-event outcome. However, many disease outcomes are time-dependent and the
      onset time can be censored. Measuring discrimination potential of a prognostic
      marker without considering time to event can lead to biased estimates. In this
      paper, we extended the NRI and IDI to time-to-event settings and derived the
      corresponding sample estimators and asymptotic tests. Simulation studies showed
      that the time-dependent NRI and IDI have better performance than Pencina's NRI
      and IDI for measuring the improved discriminatory power of a new risk marker in
      prognostic survival models.

PMID- 22984362
TI  - Development of a competitive fluorescence-based synaptosome binding assay for
      brevetoxins.
AB  - Brevetoxins are a family of ladder-frame polyether toxins produced during blooms
      of the marine dinoflagellate Karenia brevis. Inhalation of brevetoxins
      aerosolized by wind and wave action can lead to asthma-like symptoms in beach
      goers. Consumption of either shellfish or finfish exposed to K. brevis blooms can
      lead to the development of neurotoxic shellfish poisoning. The toxic effects of
      brevetoxins are due to activation of voltage-sensitive sodium channels (VSSCs) in
      cell membranes. Binding of brevetoxin analogs and competitors to site 5 on these
      channels has historically been measured using a radioligand competition assay
      that is fraught with difficulty, including slow analysis time, production of
      radioactive waste, and cumbersome and expensive methods associated with the
      generation of radioactive labeled ligands. In this study, we describe the
      development of a novel fluorescent synaptosome binding assay for the brevetoxin
      receptor. BODIPY((r))-conjugated to PbTx-2 was used as the labeled ligand. The
      BODIPY((r))-PbTx-2 conjugate was found to displace [(3)H]-PbTx-3 from its binding
      site on VSSCs on rat brain synaptosomes with an equilibrium inhibition constant
      of 0.11 nM. We have shown that brevetoxin A and B analogs are all able to compete
      for binding with the fluorescent ligand. Most importantly, this assay was
      validated against the current site 5 receptor binding assay standard, the
      radioligand receptor assay for the brevetoxin receptor using [(3)H]-PbTx-3 as the
      labeled ligand. The fluorescence based assay yielded equilibrium inhibition
      constants comparable to the radioligand assay for all brevetoxin analogs. The
      fluorescence based assay was quicker, far less expensive, and did not generate
      radioactive waste or need radioactive facilities. As such, this fluorescence
      based assay can be used to replace the current radioligand assay for site 5 on
      voltage-sensitive sodium channels and will be a vital tool for future experiments
      examining the binding affinity of various ligands for site 5 on sodium channels.

PMID- 22984364
TI  - A Multinomial Ordinal Probit Model with Singular Value Decomposition Method for a
      Multinomial Trait.
AB  - We developed a multinomial ordinal probit model with singular value decomposition
      for testing a large number of single nucleotide polymorphisms SNPs simultaneously
      for association with multidisease status when sample size is much smaller than
      the number of SNPs. The validity and performance of the method was evaluated via
      simulation. We applied the method to our real study sample recruited through the
      Mexican-American Coronary Artery Disease study. We found 3 genes SORCS1, AMPD1,
      and PPARalpha to be associated with the development of both IGT and IFG, while 5
      genes AMPD2, PRKAA2, C5, TCF7L2, and ITR with the IGT mechanism only and 6 genes
      CAPN10, IL4, NOS3, CD14, GCG, and SORT1 with the IFG mechanism only. These data
      suggest that IGT and IFG may indicate different physiological mechanism to
      prediabetes, via different genetic determinants.

PMID- 22984363
TI  - Gore BioA Fistula Plug in the treatment of high anal fistulas--initial results
      from a German multicenter-study.
AB  - BACKGROUND: Treatment of high anal fistulas may be associated with a high risk of
      continence disorders. Beside traditional procedure of flap-reconstruction the
      occlusion of the fistula tract using fistula-plugs offers a new sphincter-saving
      treatment option. In this study for the first time results from Germany are
      described. PATIENTS AND METHOD: 40 patients (30 male, 10 female, age 51 +/- 12
      years) underwent closure of a high trans-sphincteric (n = 28) or supra
      sphincteric (n = 12) fistula with Gore BioA Fistula Plug((r)) in three surgical
      departments. The surgical procedures had been performed by five colorectal
      surgeons. Four patients had Crohn's disease. Preoperatively 33 patients were
      completely continent; seven patients complained of minor continence disorders.
      Treatment of the patients was performed on a intent-to-treat basis and evaluation
      of the results was retrospective using pooled data from each center. RESULTS:
      Postoperatively one patient developed an abscess, which had to be managed
      surgically. In two patients the plug had fallen out within the first two weeks
      postoperatively. Six months after surgery the fistula has been healed in 20
      patients (50.0%). Three additional fistulas healed after 7, 9 rsp. 12 months. The
      overall healing-rate was 57.5% (23/40). The healing rate differs considerably
      between the surgeons from 0 to 75% and depends on the number of previous
      interventions. In patients having only drainage of the abscess success occurred
      in 63.6% (14/22) whereas in patients after one or more flap fistula
      reconstruction the healing rate decreased slightly to 50% (9/18). No patient
      complained about any impairment of his preoperative continence status.
      CONCLUSION: By occlusion of high anal fistulas with a plug technique definitive
      healing could be achieved in nearly every second patients. Previous surgery seems
      to have a negative impact on success rate. We have not observed any negative
      impact on anal continence. From that point of view anal fistula plugs might be
      discussed as a treatment option for high anal fistulas, but further studies are
      needed to gain conclusive evidence.

PMID- 22984365
TI  - Population-based screening in the era of genomics.
AB  - To date, risk profiles based on the known common susceptibility variants have
      limited value in predicting risk of disease but they could be used for risk
      stratification in prevention programmes at population level. We illustrate the
      potential utility of polygenic risk stratification using the case of population
      based screening for prostate and breast cancer. We compared the number of
      individuals eligible for screening and the number of cases potentially detectable
      by screening in a population undergoing screening based on age alone with a
      population undergoing stratified screening based on age and polygenic risk
      profile. Stratified screening strategy based on age and genetic risk would
      potentially improve the efficiency of screening programmes and reduce their
      adverse consequences. Organisational, ethical, legal and social issues need to be
      addressed before stratified screening programmes could be implemented.

PMID- 22984366
TI  - Examining the Family Context and Relations with Attitudes to School and
      Scholastic Competence.
AB  - The importance of family relations in children's adjustment has been established,
      but questions remain about the contexts that account for these associations.
      Examining children's reactions to family stress holds promise for advancing our
      understanding of the relations between attachment and school-related outcomes.
      The present study examined children's attachment, basal cortisol, and emotional
      reactions in 235 community families, to understand contributions to children's
      attitudes to school and scholastic competence. Children's attachment security and
      normative basal cortisol both contributed to positive school outcomes, while
      insecurity in the context of low or high cortisol and emotional distress related
      negatively. Findings highlight the importance of examining stress in family
      contexts to advance the understanding of children's school functioning, with
      implications for school mental health interventions.

PMID- 22984367
TI  - A within-subject ERP and fMRI investigation of orientation-specific recognition
      memory for pictures.
AB  - Despite a large body of recognition memory research, its temporal, measured with
      ERPs, and spatial, measured with fMRI, substrates have never been investigated in
      the same subjects. In the present study, we obtained this information in parallel
      sessions, in which subjects studied and recognized images of visual objects and
      their orientation. The results showed that ERP-familiarity processes between 240
      and 440 ms temporally preceded recollection processes and were structurally
      associated with prefrontal brain regions. Recollection processes were most
      prominent from 440 to 600 ms and correlated with activation in temporal,
      parietal, and occipital brain regions. Post-retrieval monitoring, which occurred
      in the ERP between 600 and 1000 ms as a long-lasting slow-wave over frontal
      channel groups, showed correlations with activation in the prefrontal and
      parietal cortex. These ERP/fMRI relationships showed some correspondences to
      source localizations of the investigated ERP memory effects.

PMID- 22984368
TI  - Anti-IL-6 receptor antibody does not ameliorate radiation pneumonia in mice.
AB  - We previously showed that early administration of monoclonal anti-interleukin-6
      receptor antibody (IL-6RA) does not prevent radiation-induced lung injury in
      mice. The purpose of this study was to investigate whether a higher dose and
      longer course of IL-6RA treatment was effective in ameliorating radiation
      pneumonia. C57Bl/6J mice received thoracic irradiation of 12 Gy, and were
      intraperitoneally injected with the IL-6RA, namely MR16-1, or with control rat
      IgG 4 times, once immediately following exposure and then weekly from 1 to 3
      weeks after irradiation. Enzyme-linked immunosorbent assays were used to analyze
      the plasma levels of IL-6 and serum amyloid A (SAA). Lung injury was assessed by
      histological staining with haematoxylin and eosin (H&E) and by measuring wet lung
      weight. We observed marked upregulation of IL-6 in IL-6RA-treated mice compared
      to the IgG-treated control group, whereas IL-6RA did not increase the production
      of SAA in the group receiving irradiation. However, radiation pneumonia, as
      evaluated by H&E staining and lung weight showed no differences between the IL
      6RA-treated mice and the controls. Long-term treatment with high-dose IL-6RA does
      not ameliorate radiation pneumonia.

PMID- 22984369
TI  - Role of acetylcholine and calcium ions in three vascular contraction models:
      Angiotensin II, phenylephrine and caffeine.
AB  - The aim of this study was to determine the role of acetylcholine and calcium ions
      in modulating the vascular contraction induced by angiotensin II (ANG II),
      phenylephrine (PHE) and caffeine. The study was performed on perfunded Wistar rat
      tail arteries. The contraction caused by ANG II, PHE and caffeine with the
      participation of intracellular [in free physiological salt solution (FPSS)] and
      extracellular [in physiological salt solution (PSS), after emptying the cellular
      stores] pools of calcium ions and the addition of L-NNA (NOSe inhibitor) or ODQ
      (GC inhibitor) was studied. Then the effect of acetylcholine on the contraction
      responses was analyzed. ANG II, PHE and caffeine induced an increase in perfusion
      pressure in PSS and FPSS. Acetylcholine reduced the contraction resulting from
      the presence of ANG II and PHE, but not caffeine. L-NNA and ODQ abolished the
      spasmolytic action of acetylcholine. Both pools of calcium ions mediated the
      action of ANG II and PHE, and caffeine induced the contraction with the
      participation of calcium released from intracellular stores. The spasmolytic
      effect of acetylcholine on responses stimulated by ANG II and PHE indicates the
      participation of nitric oxide in modulating the reactivity of the arteries on the
      studied agonists of the metabotropic receptors. No observed acetylcholine effect
      on caffeine suggests that the pathway associated with nitric oxide does not
      interfere with the contraction induced by the ryanodin receptor.

PMID- 22984370
TI  - HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection.
AB  - Epithelial ovarian cancer has the highest mortality of all gynecological cancers,
      and its progression is often without symptoms. Clinical outcome and survival may
      be improved if the disease is identified in the early stages. The objective of
      the study was to evaluate the utility of the serum biomarkers human epididymis
      protein 4 (HE4), soluble mesothelin-related protein (SMRP) and CA125 in the
      detection of ovarian cancer. In this retrospective study, the serum
      concentrations of CA125, HE4 protein and SMRP were measured in a cohort of 70
      patients with epithelial ovarian cancer (EOC) compared with 78 healthy controls.
      Median serum levels of CA125 for ovarian cancer cases were 503.55+/-560.7 U/ml
      vs. 9.28+/-14.47 U/ml in the control group (p<0.001); for SMRP 5.13+/-7.64 nM vs.
      1.02+/-0.89 nM (p<0.01); and for HE4 597.95+/-934.59 pM vs. 56.75+/-43.79 pM
      (p<0.001), respectively. Positive correlations between the clinical stage of EOC
      and CA125, HE4 and SMRP serum concentrations were found [(R=0.83; p<0.001);
      (R=0.64; p<0.001); (R=0.45; p<0.001), respectively]. Data analysis for the whole
      study group also revealed a significant correlation between plasma concentrations
      of CA125 and HE4 (R=0.45; p<0.001), between CA125 and SMRP (R=0.38; p<0.001) as
      well as HE4 and SMRP (R=0.51; p<0.001). Similar significant correlations between
      serum biomarker concentrations were also found in the ovarian cancer group [CA125
      and HE4 (R=0.31; p<0.01); CA125 and SMRP (R=0.25; p<0.05); HE4 and SMRP (R=0.44,
      p<0.001), respectively]. A significant correlation was observed between the
      serous histological type of EOC and serum concentration of HE4 in the study group
      compared with other non-serous types of ovarian cancer (p<0.01). In conclusion,
      measuring CA125 in combination with new biomarkers such as SMRP and HE4 may
      improve the accuracy of ovarian cancer diagnosis, particularly in early detection
      of the disease.

PMID- 22984371
TI  - Bone graft substitutes for the treatment of traumatic fractures of the
      extremities.
AB  - HEALTH POLITICAL AND SCIENTIFIC BACKGROUND: Bone graft substitutes are
      increasingly being used as supplements to standard care or as alternative to bone
      grafts in the treatment of traumatic fractures. RESEARCH QUESTIONS: The efficacy
      and cost-effectiveness of bone graft substitutes for the treatment of traumatic
      fractures as well as the ethical, social and legal implications of their use are
      the main research questions addressed. METHODS: A systematic literature search
      was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December
      2009. Randomised controlled trials (RCT), where applicable also containing
      relevant health economic evaluations and publications addressing the ethical,
      social and legal aspects of using bone graft substitutes for fracture treatment
      were included in the analysis. After assessment of study quality the information
      synthesis of the medical data was performed using metaanalysis, the synthesis of
      the health economic data was performed descriptively. RESULTS: 14 RCT were
      included in the medical analysis, and two in the heath economic evaluation. No
      relevant publications on the ethical, social and legal implications of the bone
      graft substitute use were found.  In the RCT on fracture treatment with bone
      morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT
      with an elevated high risk of bias) there was a significant difference in favour
      of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement
      and bone marrow-based composite materials versus autogenous bone grafts (RCT with
      a high risk of bias) revealed significant differences in favour of bone graft
      substitutes for some outcome measures. Regarding the other bone graft
      substitutes, almost all comparisons demonstrated no significant difference. The
      use of BMP-2 in addition to standard care without bone grafting led in the study
      to increased treatment costs considering all patients with traumatic open
      fractures. However, cost savings through the additional use of BMP-2 were
      calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson
      grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous
      bone grafts as well as for other bone graft substitutes in fracture treatment has
      not been determined yet. DISCUSSION: Although there were some significant
      differences in favour of BMP-2, due to the overall poor quality of the studies
      the evidence can only be interpreted as suggestive for efficacy. In the case of
      CaP cements and bone marrow-based bone substitute materials, the evidence is only
      weakly suggestive for efficacy. From an overall economic perspective, the
      transferability of the results of the health economic evaluations to the current
      situation in Germany is limited. CONCLUSIONS: The current evidence is
      insufficient to evaluate entirely the use of different bone graft substitutes for
      fracture treatment. From a medical point of view, BMP-2 is a viable alternative
      for treatment of open fractures of the tibia, especially in cases where bone
      grafting is not possible. Autologous bone grafting is preferable comparing to the
      use of OP-1. Possible advantages of CaP cements and composites containing bone
      marrow over autogenous bone grafting should be taken into account in clinical
      decision making. The use of the hydroxyapatite material and allograft bone chips
      compared to autologous bone grafts cannot be recommended.  From a health economic
      perspective, the use of BMP-2 in addition to standard care without bone grafting
      is recommended as cost-saving in patients with high-grade open fractures (Gustilo
      Anderson grade IIIB). Based on the current evidence no further recommendations
      can be made regarding the use of bone graft substitutes for the treatment of
      fractures. To avoid legal implications, use of bone graft substitutes outside
      their approved indications should be avoided.

PMID- 22984372
TI  - Therapy of the burnout syndrome.
AB  - BACKGROUND: The prevalence, diagnostics and therapy of the burnout syndrome are
      increasingly discussed in the public. The unclear definition and diagnostics of
      the burnout syndrome are scientifically criticized. There are several therapies
      with unclear evidence for the treatment of burnout in existence. OBJECTIVES: The
      health technology assessment (HTA) report deals with the question of usage and
      efficacy of different burnout therapies. METHODS: For the years 2006 to 2011, a
      systematic literature research was done in 31 electronic databases (e.g. EMBASE,
      MEDLINE, PsycINFO). Important inclusion criteria are burnout, therapeutic
      intervention and treatment outcome. RESULTS: 17 studies meet the inclusion
      criteria and are regarded for the HTA report. The studies are very heterogeneous
      (sample size, type of intervention, measuring method, level of evidence). Due to
      their study design (e.g. four reviews, eight randomized controlled trials) the
      studies have a comparable high evidence: three times 1A, five times 1B, one time
      2A, two times 2B and six times 4. 13 of the 17 studies are dealing with the
      efficacy of psychotherapy and psychosocial interventions for the reduction of
      burnout (partly in combination with other techniques). Cognitive behaviour
      therapy leads to the improvement of emotional exhaustion in the majority of the
      studies. The evidence is inconsistent for the efficacy of stress management and
      music therapy. Two studies regarding the efficacy of Qigong therapy do not
      deliver a distinct result. One study proves the efficacy of roots of Rhodiola
      rosea (evidence level 1B). Physical therapy is only in one study separately
      examined and does not show a better result than standard therapy. DISCUSSION:
      Despite the number of studies with high evidence the results for the efficacy of
      burnout therapies are preliminary and do have only limited reach. The authors of
      the studies complain about the low number of skilled studies for the therapy of
      burnout. Furthermore, they point to the insufficient evaluation of the therapy
      studies and the need for further research. Some authors report the effects of
      considerable natural recovering. Numerous limitations affect the quality of the
      results. Intervention contents and duration, study design and study size are very
      diverse and do not permit direct comparison. Most of the samples are small by
      size with low statistical power, long-term follow-ups are missing. Comorbidities
      and parallel utilized therapies are insufficient documented or controlled. Most
      of the studies use the Maslach Burnout Inventory (MBI) as diagnostic or outcome
      tool, but with different cut-off-points. It should be noticed that the validity
      of the MBI as diagnostic tool is not proved. Ethical, juridical and social
      determining factors are not covered or discussed in the studies. CONCLUSION: The
      efficacy of therapies for the treatment of the burnout syndrome is insufficient
      investigated. Only for cognitive behavioural therapy (CBT) exists an adequate
      number of studies which prove its efficacy. Big long-term experimental studies
      are missing which compare the efficacy of the single therapies and evaluate their
      evidence. The natural recovering without any therapy needs further research.
      Additionally, it has to be examined to what extent therapies and their possible
      effects are thwarted by the conditions of the working place and the working
      conditions.

PMID- 22984373
TI  - Federal structures of the prevention of alcohol misuse among children and youths.

PMID- 22984374
TI  - Nanoscale Science and Technology and People with Disabilities in Asia: An Ability
      Expectation Analysis.
AB  - Science and technology, including nanoscale science and technology, influences
      and is influenced by various discourses and areas of action. Ableism is one
      concept and ability expectation is one dynamic that impacts the direction,
      vision, and application of nanoscale science and technology and vice versa. At
      the same time, policy documents that involve or relate to disabled people exhibit
      ability expectations of disabled people. The authors present ability expectations
      exhibited within two science and technology direction documents from Asia, as
      well as in two policy documents generated and influenced by disabled people from
      Asia. As well, the authors discuss the impact of the ability expectations
      exhibited in these four documents with respect to the relationship between
      science and technology and disabled people.

PMID- 22984375
TI  - Community engagement on the Thai-Burmese border: rationale, experience and
      lessons learnt.
AB  - Community engagement is increasingly promoted in developing countries, especially
      in international health research, but there is little published experience. The
      Shoklo Malaria Research Unit (SMRU) conducts research with refugees, migrant
      workers, displaced people, and day migrants on the Thai-Burmese border, and has
      recently facilitated the set up of the Tak Province Border Community Ethics
      Advisory Board (T-CAB). Valuable lessons have been learnt from consultation with
      the T-CAB especially in the area of participant recruitment and the informed
      consent process. A lot of new research questions have emerged from consultation
      with the T-CAB. This paper describes our experience, lessons learnt and the
      unique challenges faced working with the T-CAB from its initial conception to
      date. We conclude that consultation with the T-CAB has made improvements in our
      research in particular operational and ethical aspects of our studies. 

PMID- 22984376
TI  - Statistical Methods for Tissue Array Images - Algorithmic Scoring and Co
      training.
AB  - Recent advances in tissue microarray technology have allowed immunohistochemistry
      to become a powerful medium-to-high throughput analysis tool, particularly for
      the validation of diagnostic and prognostic biomarkers. However, as study size
      grows, the manual evaluation of these assays becomes a prohibitive limitation; it
      vastly reduces throughput and greatly increases variability and expense. We
      propose an algorithm-Tissue Array Co-Occurrence Matrix Analysis (TACOMA)-for
      quantifying cellular phenotypes based on textural regularity summarized by local
      inter-pixel relationships. The algorithm can be easily trained for any staining
      pattern, is absent of sensitive tuning parameters and has the ability to report
      salient pixels in an image that contribute to its score. Pathologists' input via
      informative training patches is an important aspect of the algorithm that allows
      the training for any specific marker or cell type. With co-training, the error
      rate of TACOMA can be reduced substantially for a very small training sample
      (e.g., with size 30). We give theoretical insights into the success of co
      training via thinning of the feature set in a high dimensional setting when there
      is "sufficient" redundancy among the features. TACOMA is flexible, transparent
      and provides a scoring process that can be evaluated with clarity and confidence.
      In a study based on an estrogen receptor (ER) marker, we show that TACOMA is
      comparable to, or outperforms, pathologists' performance in terms of accuracy and
      repeatability.

PMID- 22984393
TI  - Acidithiobacillus caldus sulfur oxidation model based on transcriptome analysis
      between the wild type and sulfur oxygenase reductase defective mutant.
AB  - BACKGROUND: Acidithiobacillus caldus (A. caldus) is widely used in bio-leaching.
      It gains energy and electrons from oxidation of elemental sulfur and reduced
      inorganic sulfur compounds (RISCs) for carbon dioxide fixation and growth.
      Genomic analyses suggest that its sulfur oxidation system involves a truncated
      sulfur oxidation (Sox) system (omitting SoxCD), non-Sox sulfur oxidation system
      similar to the sulfur oxidation in A. ferrooxidans, and sulfur oxygenase
      reductase (SOR). The complexity of the sulfur oxidation system of A. caldus
      generates a big obstacle on the research of its sulfur oxidation mechanism.
      However, the development of genetic manipulation method for A. caldus in recent
      years provides powerful tools for constructing genetic mutants to study the
      sulfur oxidation system. RESULTS: An A. caldus mutant lacking the sulfur
      oxygenase reductase gene (sor) was created and its growth abilities were measured
      in media using elemental sulfur (S(0)) and tetrathionate (K(2)S(4)O(6)) as the
      substrates, respectively. Then, comparative transcriptome analysis (microarrays
      and real-time quantitative PCR) of the wild type and the Deltasor mutant in S(0)
      and K(2)S(4)O(6) media were employed to detect the differentially expressed genes
      involved in sulfur oxidation. SOR was concluded to oxidize the cytoplasmic
      elemental sulfur, but could not couple the sulfur oxidation with the electron
      transfer chain or substrate-level phosphorylation. Other elemental sulfur
      oxidation pathways including sulfur diooxygenase (SDO) and heterodisulfide
      reductase (HDR), the truncated Sox pathway, and the S(4)I pathway for hydrolysis
      of tetrathionate and oxidation of thiosulfate in A. caldus are proposed according
      to expression patterns of sulfur oxidation genes and growth abilities of the wild
      type and the mutant in different substrates media. CONCLUSION: An integrated
      sulfur oxidation model with various sulfur oxidation pathways of A. caldus is
      proposed and the features of this model are summarized.

PMID- 22984394
TI  - Oxygen glucose deprivation in rat hippocampal slice cultures results in
      alterations in carnitine homeostasis and mitochondrial dysfunction.
AB  - Mitochondrial dysfunction characterized by depolarization of mitochondrial
      membranes and the initiation of mitochondrial-mediated apoptosis are pathological
      responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism
      directly supports mitochondrial metabolism by shuttling long chain fatty acids
      across the inner mitochondrial membrane for beta-oxidation. Our previous studies
      have shown that HI disrupts carnitine homeostasis in neonatal rats and that L
      carnitine can be neuroprotective. Thus, this study was undertaken to elucidate
      the molecular mechanisms by which HI alters carnitine metabolism and to begin to
      elucidate the mechanism underlying the neuroprotective effect of L-carnitine
      (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we
      found that oxygen glucose deprivation (OGD) decreased the levels of free
      carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in
      carnitine homeostasis correlated with decreases in the protein levels of
      carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the
      decrease in CPT1 and CPT2, enhanced both FC and the AC?FC ratio and increased
      slice culture metabolic viability, the mitochondrial membrane potential prior to
      OGD and prevented the subsequent loss of neurons during later stages of
      reperfusion through a reduction in apoptotic cell death. Finally, we found that
      LCAR supplementation preserved the structural integrity and synaptic transmission
      within the hippocampus after OGD. Thus, we conclude that LCAR supplementation
      preserves the key enzymes responsible for maintaining carnitine homeostasis and
      preserves both cell viability and synaptic transmission after OGD.

PMID- 22984395
TI  - Transgenerational inheritance of modified DNA methylation patterns and enhanced
      tolerance induced by heavy metal stress in rice (Oryza sativa L.).
AB  - BACKGROUND: DNA methylation is sensitive and responsive to stressful
      environmental conditions. Nonetheless, the extent to which condition-induced
      somatic methylation modifications can impose transgenerational effects remains to
      be fully understood. Even less is known about the biological relevance of the
      induced epigenetic changes for potentially altered well-being of the organismal
      progenies regarding adaptation to the specific condition their progenitors
      experienced. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed DNA methylation pattern
      by gel-blotting at genomic loci representing transposable elements and protein
      coding genes in leaf-tissue of heavy metal-treated rice (Oryza sativa) plants
      (S0), and its three successive organismal generations. We assessed expression of
      putative genes involved in establishing and/or maintaining DNA methylation
      patterns by reverse transcription (RT)-PCR. We measured growth of the stressed
      plants and their unstressed progenies vs. the control plants. We found (1)
      relative to control, DNA methylation patterns were modified in leaf-tissue of the
      immediately treated plants, and the modifications were exclusively confined to
      CHG hypomethylation; (2) the CHG-demethylated states were heritable via both
      maternal and paternal germline, albeit often accompanying further
      hypomethylation; (3) altered expression of genes encoding for DNA
      methyltransferases, DNA glycosylase and SWI/SNF chromatin remodeling factor
      (DDM1) were induced by the stress; (4) progenies of the stressed plants exhibited
      enhanced tolerance to the same stress their progenitor experienced, and this
      transgenerational inheritance of the effect of condition accompanying
      heritability of modified methylation patterns. CONCLUSIONS/SIGNIFICANCE: Our
      findings suggest that stressful environmental condition can produce
      transgenerational epigenetic modifications. Progenies of stressed plants may
      develop enhanced adaptability to the condition, and this acquired trait is
      inheritable and accord with transmission of the epigenetic modifications. We
      suggest that environmental induction of heritable modifications in DNA
      methylation provides a plausible molecular underpinning for the still contentious
      paradigm of inheritance of acquired traits originally put forward by Jean
      Baptiste Lamarck more than 200 years ago.

PMID- 22984396
TI  - PTFOS: flexible and absorbable intracranial electrodes for magnetic resonance
      imaging.
AB  - Intracranial electrocortical recording and stimulation can provide unique
      knowledge about functional brain anatomy in patients undergoing brain surgery.
      This approach is commonly used in the treatment of medically refractory epilepsy.
      However, it can be very difficult to integrate the results of cortical recordings
      with other brain mapping modalities, particularly functional magnetic resonance
      imaging (fMRI). The ability to integrate imaging and electrophysiological
      information with simultaneous subdural electrocortical recording/stimulation and
      fMRI could offer significant insight for cognitive and systems neuroscience as
      well as for clinical neurology, particularly for patients with epilepsy or
      functional disorders. However, standard subdural electrodes cause significant
      artifact in MRI images, and concerns about risks such as cortical heating have
      generally precluded obtaining MRI in patients with implanted electrodes. We
      propose an electrode set based on polymer thick film organic substrate (PTFOS),
      an organic absorbable, flexible and stretchable electrode grid for intracranial
      use. These new types of MRI transparent intracranial electrodes are based on nano
      particle ink technology that builds on our earlier development of an EEG/fMRI
      electrode set for scalp recording. The development of MRI-compatible
      recording/stimulation electrodes with a very thin profile could allow functional
      mapping at the individual subject level of the underlying feedback and feed
      forward networks. The thin flexible substrate would allow the electrodes to
      optimally contact the convoluted brain surface. Performance properties of the
      PTFOS were assessed by MRI measurements, finite difference time domain (FDTD)
      simulations, micro-volt recording, and injecting currents using standard
      electrocortical stimulation in phantoms. In contrast to the large artifacts
      exhibited with standard electrode sets, the PTFOS exhibited no artifact due to
      the reduced amount of metal and conductivity of the electrode/trace ink and had
      similar electrical properties to a standard subdural electrode set. The enhanced
      image quality could enable routine MRI exams of patients with intracranial
      electrode implantation and could also lead to chronic implantation solutions.

PMID- 22984397
TI  - Differential regulation of transcription factors by location-specific EGF
      receptor signaling via a spatio-temporal interplay of ERK activation.
AB  - It is well established that EGFR signals from both the plasma membrane (PM) and
      endosome (EN). However, very little is known about whether and how the EGFR
      signals at the PM and EN to differentially regulate various signaling pathways
      and the physiological outcomes. In this communication, we established a system
      that allowed the specific activations of EGFR at different cell locations: PM and
      EN. PM activation of EGFR is achieved by activation of endocytosis-deficient
      mutant EGFR1010LL/AA stably expressed in CHO cells (CHO-LL/AA cell). EN
      activation of EGFR is achieved by activating the wild type EGFR stably expressed
      in CHO cells (CHO-EGFR cell) after its internalization into EN with a previously
      reported protocol. We showed that both EGFR activations at PM and EN activated
      ERK to a similar level, but differentially stimulated transcriptional factors c
      jun and c-fos. We further showed that EGFR activations at PM and EN resulted in
      differential spatio-temporal dynamics of phosphorylated ERK which caused the
      differential activation of two downstream substrates ELK1 and RSK. Finally we
      showed that EGFR signaling from PM and EN led to different physiological
      outcomes. CHO-LL/AA cells that only generate PM EGFR signals have a larger cell
      size and slower proliferation rate than CHO-EGFR cells. We conclude that location
      specific EGFR activation differentially regulates cell functions through a spatio
      temporal interplay of ERK activation.

PMID- 22984398
TI  - Comorbid externalising behaviour in AD/HD: evidence for a distinct pathological
      entity in adolescence.
AB  - While the profiling of subtypes of Attention Deficit Hyperactivity Disorder
      (AD/HD) have been the subject of considerable scrutiny, both psychometrically and
      psychophysiologically, little attention has been paid to the effect of diagnoses
      comorbid with AD/HD on such profiles. This is despite the greater than 80%
      prevalence of comorbidity under the DSM-IV-TR diagnostic definitions. Here we
      investigate the event related potential (ERP) and psychometric profiles of
      Controls, AD/HD, and comorbid AD/HD (particularly AD/HD+ODD/CD) groups on six
      neurocognitive tasks thought to probe the constructs of selective and sustained
      attention, response inhibition and executive function. Data from 29 parameters
      extracted from a child group (age range 6 to 12; 52 Controls and 64 AD/HD) and
      from an adolescent group (age range 13 to 17; 79 Controls and 88 AD/HD) were
      reduced via a Principal Components Analysis, the 6 significant eigenvectors then
      used as determinants of cluster membership via a Two-Step Cluster Analysis. Two
      clusters were found in the analysis of the adolescent age group--a cluster
      dominated by Control and AD/HD participants without comorbidity, while the second
      cluster was dominated by AD/HD participants with externalising comorbidity
      (largely oppositional defiant/conduct disorder ODD/CD). A similar segregation
      within the child age group was not found. Further analysis of these objectively
      determined clusters in terms of their clinical diagnoses indicates a significant
      effect of ODD/CD comorbidity on a concurrent AD/HD diagnosis. We conclude that
      comorbid externalising behaviour in AD/HD constitutes a distinct pathological
      entity in adolescence.

PMID- 22984399
TI  - Four new bat species (Rhinolophus hildebrandtii complex) reflect Plio-Pleistocene
      divergence of dwarfs and giants across an Afromontane archipelago.
AB  - Gigantism and dwarfism evolve in vertebrates restricted to islands. We describe
      four new species in the Rhinolophus hildebrandtii species-complex of horseshoe
      bats, whose evolution has entailed adaptive shifts in body size. We postulate
      that vicissitudes of palaeoenvironments resulted in gigantism and dwarfism in
      habitat islands fragmented across eastern and southern Africa. Mitochondrial and
      nuclear DNA sequences recovered two clades of R. hildebrandtii senso lato which
      are paraphyletic with respect to a third lineage (R. eloquens). Lineages differ
      by 7.7 to 9.0% in cytochrome b sequences. Clade 1 includes R. hildebrandtii sensu
      stricto from the east African highlands and three additional vicariants that
      speciated across an Afromontane archipelago through the Plio-Pleistocene,
      extending from the Kenyan Highlands through the Eastern Arc, northern Mozambique
      and the Zambezi Escarpment to the eastern Great Escarpment of South Africa. Clade
      2 comprises one species confined to lowland savanna habitats (Mozambique and
      Zimbabwe). A third clade comprises R. eloquens from East Africa. Speciation
      within Clade 1 is associated with fixed differences in echolocation call
      frequency, and cranial shape and size in populations isolated since the late
      Pliocene (ca 3.74 Mya). Relative to the intermediate-sized savanna population
      (Clade 2), these island-populations within Clade 1 are characterised by either
      gigantism (South African eastern Great Escarpment and Mts Mabu and Inago in
      Mozambique) or dwarfism (Lutope-Ngolangola Gorge, Zimbabwe and Soutpansberg
      Mountains, South Africa). Sympatry between divergent clades (Clade 1 and Clade 2)
      at Lutope-Ngolangola Gorge (NW Zimbabwe) is attributed to recent range
      expansions. We propose an "Allometric Speciation Hypothesis", which attributes
      the evolution of this species complex of bats to divergence in constant frequency
      (CF) sonar calls. The origin of species-specific peak frequencies (overall range
      = 32 to 46 kHz) represents the allometric effect of adaptive divergence in skull
      size, represented in the evolution of gigantism and dwarfism in habitat islands.

PMID- 22984400
TI  - MLVA based classification of Mycobacterium tuberculosis complex lineages for a
      robust phylogeographic snapshot of its worldwide molecular diversity.
AB  - Multiple-locus variable-number tandem repeat analysis (MLVA) is useful to
      establish transmission routes and sources of infections for various
      microorganisms including Mycobacterium tuberculosis complex (MTC). The recently
      released SITVITWEB database contains 12-loci Mycobacterial Interspersed
      Repetitive Units--Variable Number of Tandem DNA Repeats (MIRU-VNTR) profiles and
      spoligotype patterns for thousands of MTC strains; it uses MIRU International
      Types (MIT) and Spoligotype International Types (SIT) to designate clustered
      patterns worldwide. Considering existing doubts on the ability of spoligotyping
      alone to reveal exact phylogenetic relationships between MTC strains, we
      developed a MLVA based classification for MTC genotypic lineages. We studied 6
      different subsets of MTC isolates encompassing 7793 strains worldwide. Minimum
      spanning trees (MST) were constructed to identify major lineages, and the most
      common representative located as a central node was taken as the prototype
      defining different phylogenetic groups. A total of 7 major lineages with their
      respective prototypes were identified: Indo-Oceanic/MIT57, East Asian and African
      Indian/MIT17, Euro American/MIT116, West African-I/MIT934, West African
      II/MIT664, M. bovis/MIT49, M.canettii/MIT60. Further MST subdivision identified
      an additional 34 sublineage MIT prototypes. The phylogenetic relationships among
      the 37 newly defined MIRU-VNTR lineages were inferred using a classification
      algorithm based on a bayesian approach. This information was used to construct an
      updated phylogenetic and phylogeographic snapshot of worldwide MTC diversity
      studied both at the regional, sub-regional, and country level according to the
      United Nations specifications. We also looked for IS6110 insertional events that
      are known to modify the results of the spoligotyping in specific circumstances,
      and showed that a fair portion of convergence leading to the currently observed
      bias in phylogenetic classification of strains may be traced back to the presence
      of IS6110. These results shed new light on the evolutionary history of the
      pathogen in relation to the history of peopling and human migration.

PMID- 22984401
TI  - The implementation and appraisal of a novel confirmatory HIV-1 testing algorithm
      in the Microbicides Development Programme 301 Trial (MDP301).
AB  - We describe the application of a novel HIV confirmatory testing algorithm to
      determine the primary efficacy endpoint in a large Phase III microbicide trial.
      9385 women were enrolled between 2005 and 2009. Of these women, 537 (6%) had at
      least one positive HIV rapid test after enrolment. This triggered the use of the
      algorithm which made use of archived serum and Buffy Coat samples. The overall
      sample set was >95% complete. 419 (78%) of the rapid test positive samples were
      confirmed as primary endpoints using a combination of assays for the detection of
      HIV-specific antibodies (EIA's and Western Blot), and for components of the virus
      itself (PCR for the detection of nucleic acids and EIA for p24 antigen). 63 (12%)
      cases were confirmed as being HIV-positive at screening or enrolment and 55 (10%)
      were confirmed as HIV negative. The testing algorithm confirmed the endpoint at
      the same visit as that of the first positive rapid test in 90% of cases and at
      the time of the preceding visit in 10% of cases. Of the 63 cases which were
      subsequently confirmed to be HIV-1 positive at or before enrolment, 54 specimens
      contained no detectable HIV antibodies at screening or enrolment. However, 43
      were positive using an EIA which detects both HIV antigen and antibody and also
      had a positive p24 antigen or HIV PCR test, which was highly suggestive of acute
      infection. There were 6 unusual cases which had undetectable HIV-1 DNA or RNA. In
      4 of the 6 cases the presence of HIV-1-specific antibodies was confirmed by
      Western Blot. One of these cases with an indeterminate Western Blot was a
      previous vaccine trial participant. The algorithm served the objectives of the
      study well and can be recommended for use in determining HIV as an endpoint in
      clinical trials. TRIAL REGISTRATION: ISRCTN.org ISRCTN 64716212.

PMID- 22984402
TI  - Melanoregulin, product of the dsu locus, links the BLOC-pathway and OA1 in
      organelle biogenesis.
AB  - Humans with Hermansky-Pudlak Syndrome (HPS) or ocular albinism (OA1) display
      abnormal aspects of organelle biogenesis. The multigenic disorder HPS displays
      broad defects in biogenesis of lysosome-related organelles including melanosomes,
      platelet dense granules, and lysosomes. A phenotype of ocular pigmentation in OA1
      is a smaller number of macromelanosomes, in contrast to HPS, where in many cases
      the melanosomes are smaller than normal. In these studies we define the role of
      the Mreg(dsu) gene, which suppresses the coat color dilution of Myo5a,
      melanophilin, and Rab27a mutant mice in maintaining melanosome size and
      distribution. We show that the product of the Mreg(dsu) locus, melanoregulin
      (MREG), interacts both with members of the HPS BLOC-2 complex and with Oa1 in
      regulating melanosome size. Loss of MREG function facilitates increase in the
      size of micromelanosomes in the choroid of the HPS BLOC-2 mutants ruby, ruby2,
      and cocoa, while a transgenic mouse overexpressing melanoregulin corrects the
      size of retinal pigment epithelium (RPE) macromelanosomes in Oa1(ko/ko) mice.
      Collectively, these results suggest that MREG levels regulate pigment
      incorporation into melanosomes. Immunohistochemical analysis localizes
      melanoregulin not to melanosomes, but to small vesicles in the cytoplasm of the
      RPE, consistent with a role for this protein in regulating membrane interactions
      during melanosome biogenesis. These results provide the first link between the
      BLOC pathway and Oa1 in melanosome biogenesis, thus supporting the hypothesis
      that intracellular G-protein coupled receptors may be involved in the biogenesis
      of other organelles. Furthermore these studies provide the foundation for
      therapeutic approaches to correct the pigment defects in the RPE of HPS and OA1.

PMID- 22984403
TI  - Statistical approaches to use a model organism for regulatory sequences
      annotation of newly sequenced species.
AB  - A major goal of bioinformatics is the characterization of transcription factors
      and the transcriptional programs they regulate. Given the speed of genome
      sequencing, we would like to quickly annotate regulatory sequences in newly
      sequenced genomes. In such cases, it would be helpful to predict sequence motifs
      by using experimental data from closely related model organism. Here we present a
      general algorithm that allow to identify transcription factor binding sites in
      one newly sequenced species by performing Bayesian regression on the annotated
      species. First we set the rationale of our method by applying it within the same
      species, then we extend it to use data available in closely related species.
      Finally, we generalise the method to handle the case when a certain number of
      experiments, from several species close to the species on which to make
      inference, are available. In order to show the performance of the method, we
      analyse three functionally related networks in the Ascomycota. Two gene network
      case studies are related to the G2/M phase of the Ascomycota cell cycle; the
      third is related to morphogenesis. We also compared the method with MatrixReduce
      and discuss other types of validation and tests. The first network is well known
      and provides a biological validation test of the method. The two cell cycle case
      studies, where the gene network size is conserved, demonstrate an effective
      utility in annotating new species sequences using all the available replicas from
      model species. The third case, where the gene network size varies among species,
      shows that the combination of information is less powerful but is still
      informative. Our methodology is quite general and could be extended to integrate
      other high-throughput data from model organisms.

PMID- 22984404
TI  - Efficient universal computing architectures for decoding neural activity.
AB  - The ability to decode neural activity into meaningful control signals for
      prosthetic devices is critical to the development of clinically useful brain-
      machine interfaces (BMIs). Such systems require input from tens to hundreds of
      brain-implanted recording electrodes in order to deliver robust and accurate
      performance; in serving that primary function they should also minimize power
      dissipation in order to avoid damaging neural tissue; and they should transmit
      data wirelessly in order to minimize the risk of infection associated with
      chronic, transcutaneous implants. Electronic architectures for brain- machine
      interfaces must therefore minimize size and power consumption, while maximizing
      the ability to compress data to be transmitted over limited-bandwidth wireless
      channels. Here we present a system of extremely low computational complexity,
      designed for real-time decoding of neural signals, and suited for highly scalable
      implantable systems. Our programmable architecture is an explicit implementation
      of a universal computing machine emulating the dynamics of a network of integrate
      and-fire neurons; it requires no arithmetic operations except for counting, and
      decodes neural signals using only computationally inexpensive logic operations.
      The simplicity of this architecture does not compromise its ability to compress
      raw neural data by factors greater than [Formula: see text]. We describe a set of
      decoding algorithms based on this computational architecture, one designed to
      operate within an implanted system, minimizing its power consumption and data
      transmission bandwidth; and a complementary set of algorithms for learning,
      programming the decoder, and postprocessing the decoded output, designed to
      operate in an external, nonimplanted unit. The implementation of the implantable
      portion is estimated to require fewer than 5000 operations per second. A proof-of
      concept, 32-channel field-programmable gate array (FPGA) implementation of this
      portion is consequently energy efficient. We validate the performance of our
      overall system by decoding electrophysiologic data from a behaving rodent.

PMID- 22984405
TI  - Bmp indicator mice reveal dynamic regulation of transcriptional response.
AB  - Cellular responses to Bmp ligands are regulated at multiple levels, both
      extracellularly and intracellularly. Therefore, the presence of these growth
      factors is not an accurate indicator of Bmp signaling activity. While a common
      approach to detect Bmp signaling activity is to determine the presence of
      phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time
      consuming and not quantitative. In order to provide a simpler readout system to
      examine the presence of Bmp signaling in developing animals, we developed BRE-gal
      mouse embryonic stem cells and a transgenic mouse line that specifically respond
      to Bmp ligand stimulation. Our reporter identifies specific transcriptional
      responses that are mediated by Smad1 and Smad4 with the Schnurri transcription
      factor complex binding to a conserved Bmp-Responsive Element (BRE), originally
      identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells
      specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE
      gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in
      many cellular sites, including extraembryonic structures and mammary glands,
      thereby making this a useful scientific tool.

PMID- 22984406
TI  - Exogenous schwann cells migrate, remyelinate and promote clinical recovery in
      experimental auto-immune encephalomyelitis.
AB  - Schwann cell (SC) transplantation is currently being discussed as a strategy that
      may promote functional recovery in patients with multiple sclerosis (MS) and
      other inflammatory demyelinating diseases of the central nervous system (CNS).
      However this assumes they will not only survive but also remyelinate demyelinated
      axons in the chronically inflamed CNS. To address this question we investigated
      the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced
      experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal
      model that reproduces the complex inflammatory demyelinating immunopathology of
      MS. We now report that SCs expressing green fluorescent protein (GFP-SCs)
      allografted after disease onset not only survive but also migrate to remyelinate
      lesions in the inflamed CNS. GFP-SCs were detected more frequently in the
      parenchyma after direct injection into the spinal cord, than via intra-thecal
      delivery into the cerebrospinal fluid. In both cases the transplanted cells
      intermingled with astrocytes in demyelinated lesions, aligned with axons and by
      twenty one days post transplantation had formed Pzero protein immunoreactive
      internodes. Strikingly, GFP-SCs transplantation was associated with marked
      decrease in clinical disease severity in terms of mortality; all GFP-SCs
      transplanted animals survived whilst 80% of controls died within 40 days of
      disease.

PMID- 22984407
TI  - Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic
      cancers.
AB  - The treatment of cancer such as oligonucleotides or peptides requires efficient
      delivery systems. A novel peptide, TMTP1, previously derived and identified in
      our laboratory showed remarkable ability to target highly metastatic tumors both
      in vitro and in vivo, even at the early stage of occult metastasis foci. TMTP1
      moderately inhibited tumor cell viability, although not enough to deem it an
      efficient killer of tumor cells. In this study, we sought to enhance the anti
      tumor activity of TMTP1. To do this, we fused it to an antimicrobial peptide,
      (D)(KLAKLAK)(2), and termed the resulting peptide TMTP1-DKK. We found that TMTP1
      DKK could trigger rapid apoptosis in human prostate and gastric cancer cells
      through both the mitochondrial-induced apoptosis pathway and the death receptor
      pathway. Furthermore, direct injection of TMTP1-DKK into mice with prostate and
      gastric xenograft cancers resulted in reduction of tumor volumes and a
      significant delay in tumor progression and metastasis in vivo. These results
      suggest that TMTP1-DKK may serve as a powerful therapeutic agent for metastatic
      tumors.

PMID- 22984408
TI  - Hierarchical reproductive allocation and allometry within a perennial bunchgrass
      after 11 years of nutrient addition.
AB  - Bunchgrasses are one of the most important plant functional groups in grassland
      ecosystems. Reproductive allocation (RA) for a bunchgrass is a hierarchical
      process; however, how bunchgrasses adjust their RAs along hierarchical levels in
      response to nutrient addition has never been addressed. Here, utilizing an 11
      year nutrient addition experiment, we examined the patterns and variations in RA
      of Agropyron cristatum at the individual, tiller and spike levels. We evaluated
      the reproductive allometric relationship at each level by type II regression
      analysis to determine size-dependent and size-independent effects on plant RA
      variations. Our results indicate that the proportion of reproductive individuals
      in A. cristatum increased significantly after 11 years of nutrient addition.
      Adjustments in RA in A. cristatum were mainly occurred at the individual and
      tiller levels but not at the spike level. A size-dependent effect was a dominant
      mechanism underlying the changes in plant RA at both individual and tiller
      levels. Likewise, the distribution of plant size was markedly changed with large
      individuals increasing after nutrient addition. Tiller-level RA may be a limiting
      factor for the adjustment of RA in A. cristatum. To the best of our knowledge,
      this study is the first to examine plant responses in terms of reproductive
      allocation and allometry to nutrient enrichment within a bunchgrass population
      from a hierarchical view. Our findings have important implications for
      understanding the mechanisms underlying bunchgrass responses in RA to future
      eutrophication due to human activities. In addition, we developed a hierarchical
      analysis method for disentangling the mechanisms that lead to variation in RA for
      perennial bunchgrasses.

PMID- 22984409
TI  - Multi-scale modeling in morphogenesis: a critical analysis of the cellular Potts
      model.
AB  - Cellular Potts models (CPMs) are used as a modeling framework to elucidate
      mechanisms of biological development. They allow a spatial resolution below the
      cellular scale and are applied particularly when problems are studied where
      multiple spatial and temporal scales are involved. Despite the increasing usage
      of CPMs in theoretical biology, this model class has received little attention
      from mathematical theory. To narrow this gap, the CPMs are subjected to a
      theoretical study here. It is asked to which extent the updating rules establish
      an appropriate dynamical model of intercellular interactions and what the
      principal behavior at different time scales characterizes. It is shown that the
      longtime behavior of a CPM is degenerate in the sense that the cells
      consecutively die out, independent of the specific interdependence structure that
      characterizes the model. While CPMs are naturally defined on finite, spatially
      bounded lattices, possible extensions to spatially unbounded systems are explored
      to assess to which extent spatio-temporal limit procedures can be applied to
      describe the emergent behavior at the tissue scale. To elucidate the mechanistic
      structure of CPMs, the model class is integrated into a general multiscale
      framework. It is shown that the central role of the surface fluctuations, which
      subsume several cellular and intercellular factors, entails substantial
      limitations for a CPM's exploitation both as a mechanistic and as a
      phenomenological model.

PMID- 22984410
TI  - EU-approved rapid tests for bovine spongiform encephalopathy detect atypical
      forms: a study for their sensitivities.
AB  - Since 2004 it become clear that atypical bovine spongiform encephalopthies (BSEs)
      exist in cattle. Whenever their detection has relied on active surveillance plans
      implemented in Europe since 2001 by rapid tests, the overall and inter-laboratory
      performance of these diagnostic systems in the detection of the atypical strains
      has not been studied thoroughly to date. To fill this gap, the present study
      reports on the analytical sensitivity of the EU-approved rapid tests for atypical
      L- and H-type and classical BSE in parallel. Each test was challenged with two
      dilution series, one created from a positive pool of the three BSE forms
      according to the EURL standard method of homogenate preparation (50% w/v) and the
      other as per the test kit manufacturer's instructions. Multilevel logistic models
      and simple logistic models with the rapid test as the only covariate were fitted
      for each BSE form analyzed as directed by the test manufacturer's dilution
      protocol. The same schemes, but excluding the BSE type, were then applied to
      compare test performance under the manufacturer's versus the water protocol. The
      IDEXX HerdChek (r) BSE-scrapie short protocol test showed the highest sensitivity
      for all BSE forms. The IDEXX(r) HerdChek BSE-scrapie ultra short protocol, the
      Prionics(r)--Check WESTERN and the AJ Roboscreen(r) BetaPrion tests showed
      similar sensitivities, followed by the Roche(r) PrionScreen, the Bio-Rad(r)
      TeSeETM SAP and the Prionics(r)--Check PrioSTRIP in descending order of
      analytical sensitivity. Despite these differences, the limit of detection of all
      seven rapid tests against the different classes of material set within a 2
      log(10) range of the best-performing test, thus meeting the European Food Safety
      Authority requirement for BSE surveillance purposes. These findings indicate that
      not many atypical cases would have been missed surveillance since 2001 which is
      important for further epidemiological interpretations of the sporadic character
      of atypical forms.

PMID- 22984411
TI  - Theoretical prediction and experimental verification of protein-coding genes in
      plant pathogen genome Agrobacterium tumefaciens strain C58.
AB  - Agrobacterium tumefaciens strain C58 is a Gram-negative soil bacterium capable of
      inducing tumors (crown galls) on many dicotyledonous plants. The genome of A.
      tumefaciens strain C58 was re-annotated based on the Z-curve method. First, all
      the 'hypothetical genes' were re-identified, and 29 originally annotated
      'hypothetical genes' were recognized to be non-coding open reading frames (ORFs).
      Theoretical evidence obtained from principal component analysis, clusters of
      orthologous groups of proteins occupation, and average length distribution showed
      that these non-coding ORFs were highly unlikely to encode proteins. Results from
      the reverse transcription-polymerase chain reaction (RT-PCR) experiments on three
      different growth stages of A. tumefaciens C58 confirmed that 23 (79%) of the
      identified non-coding ORFs have no transcripts in these growth stages. In
      addition, using theoretical prediction, 19 potential protein-coding genes were
      predicted to be new protein-coding genes. Fifteen (79%) of these genes were
      verified with RT-PCR experiments. The RT-PCR experimental results confirmed the
      reliability of our theoretical prediction, indicating that false-positive
      prediction and missing genes always exist in the annotation of A. tumefaciens C58
      genome. The improved annotation will serve as a valuable resource for the
      research of the lifestyle, metabolism, and pathogenicity of A. tumefaciens C58.
      The re-annotation of A. tumefaciens C58 can be obtained from
      http://211.69.128.148/Atum/.

PMID- 22984412
TI  - Endothelial gamma-glutamyltransferase contributes to the vasorelaxant effect of S
      nitrosoglutathione in rat aorta.
AB  - S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide
      ((*)NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be
      catalyzed by gamma-glutamyltransferase (GGT). We investigated whether vascular
      GGT influences the vasorelaxant effect of GSNO in isolated rat aorta.
      Histochemical localization of GGT and measurement of its activity were performed
      by using chromogenic substrates in sections and in aorta homogenates,
      respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO
      consumption rate (absorbance decay at 334 nm), (*)NO release was visualized and
      quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The
      vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the
      presence or absence of endothelium). The role of GGT was assessed by stimulating
      enzyme activity with cosubstrate glycylglycine, as well as using two independent
      inhibitors, competitive serine borate complex and non-competitive acivicin.
      Specific GGT activity was histochemically localized in the endothelium.
      Consumption of GSNO and release of free (*)NO decreased and increased in presence
      of serine borate complex and glycylglycine, respectively. In vasorelaxation
      experiments with endothelium-intact aorta, the half maximal effective
      concentration of GSNO (EC50 = 3.2 +/- 0.5.10(-7) M) increased in the presence of
      the two distinct GGT inhibitors, serine borate complex (1.6 +/- 0.2.10(-6) M) and
      acivicin (8.3 +/- 0.6.10(-7) M), while it decreased with glycylglycine (4.7 +/-
      0.9.10(-8) M). In endothelium-denuded aorta, EC(50) for GSNO alone increased to
      2.3 +/- 0.3.10(-6) M, with no change in the presence of serine borate complex.
      These data demonstrate the important role of endothelial GGT activity in
      mediating the vasorelaxant effect of GSNO in rat aorta under physiological
      conditions. Because therapeutic treatments based on GSNO are presently under
      development, this endothelium-dependent mechanism involved in the vascular
      effects of GSNO should be taken into account in a pharmacological perspective.

PMID- 22984413
TI  - Functional adaptation in female rats: the role of estrogen signaling.
AB  - BACKGROUND: Sex steroids have direct effects on the skeleton. Estrogen acts on
      the skeleton via the classical genomic estrogen receptors alpha and beta (ERalpha
      and ERbeta), a membrane ER, and the non-genomic G-protein coupled estrogen
      receptor (GPER). GPER is distributed throughout the nervous system, but little is
      known about its effects on bone. In male rats, adaptation to loading is
      neuronally regulated, but this has not been studied in females.
      METHODOLOGY/PRINCIPAL FINDINGS: We used the rat ulna end-loading model to induce
      an adaptive modeling response in ovariectomized (OVX) female Sprague-Dawley rats.
      Rats were treated with a placebo, estrogen (17beta-estradiol), or G-1, a GPER
      specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic
      loading of the right ulna; half of the rats in each group had brachial plexus
      anesthesia (BPA) of the loaded limb before loading. Ten days after loading, serum
      estrogen concentrations, dorsal root ganglion (DRG) gene expression of ERalpha,
      ERbeta, GPER, CGRPalpha, TRPV1, TRPV4 and TRPA1, and load-induced skeletal
      responses were quantified. We hypothesized that estrogen and G-1 treatment would
      influence skeletal responses to cyclic loading through a neuronal mechanism. We
      found that estrogen suppresses periosteal bone formation in female rats. This
      physiological effect is not GPER-mediated. We also found that absolute
      mechanosensitivity in female rats was decreased, when compared with male rats.
      Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced.
      CONCLUSIONS: Estrogen acts to decrease periosteal bone formation in female rats
      in vivo. This effect is not GPER-mediated. Gender differences in absolute bone
      mechanosensitivity exist in young Sprague-Dawley rats with reduced
      mechanosensitivity in females, although underlying bone formation rate associated
      with growth likely influences this observation. In contrast to female and male
      rats, central neuronal signals had a diminished effect on adaptive bone formation
      in estrogen-deficient female rats.

PMID- 22984414
TI  - Scholarometer: a social framework for analyzing impact across disciplines.
AB  - The use of quantitative metrics to gauge the impact of scholarly publications,
      authors, and disciplines is predicated on the availability of reliable usage and
      annotation data. Citation and download counts are widely available from digital
      libraries. However, current annotation systems rely on proprietary labels, refer
      to journals but not articles or authors, and are manually curated. To address
      these limitations, we propose a social framework based on crowdsourced
      annotations of scholars, designed to keep up with the rapidly evolving
      disciplinary and interdisciplinary landscape. We describe a system called
      Scholarometer, which provides a service to scholars by computing citation-based
      impact measures. This creates an incentive for users to provide disciplinary
      annotations of authors, which in turn can be used to compute disciplinary
      metrics. We first present the system architecture and several heuristics to deal
      with noisy bibliographic and annotation data. We report on data sharing and
      interactive visualization services enabled by Scholarometer. Usage statistics,
      illustrating the data collected and shared through the framework, suggest that
      the proposed crowdsourcing approach can be successful. Secondly, we illustrate
      how the disciplinary bibliometric indicators elicited by Scholarometer allow us
      to implement for the first time a universal impact measure proposed in the
      literature. Our evaluation suggests that this metric provides an effective means
      for comparing scholarly impact across disciplinary boundaries.

PMID- 22984415
TI  - Impulsivities and Parkinson's disease: delay aversion is not worsened by Deep
      Brain Stimulation of the subthalamic nucleus.
AB  - Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) improves motor
      symptoms in Parkinson's disease (PD), but can exert detrimental effects on
      impulsivity. These effects are especially related to the inability to slow down
      when high-conflict choices have to be made. However, the influence that DBS has
      on delay aversion is still under-investigated. Here, we tested a group of 21 PD
      patients on and off stimulation (off medication) by using the Cambridge Gamble
      Task (CGT), a computerized task that allows the investigation of risk-related
      behaviours and delay aversion, and psychological questionnaires such as the
      Barratt Impulsiveness Scale (BIS), the Sensitivity to Punishment and to Reward
      Questionnaire (SPSRQ), and the Quick Delay Questionnaire (QDQ). We found that
      delay aversion scores on the CGT were no higher when patients were on stimulation
      as compared to when they were off stimulation. In contrast, PD patients reported
      feeling more impulsive in the off stimulation state, as revealed by significantly
      higher scores on the BIS. Higher scores on the sensitivity to punishment subscale
      of the SPSRQ highlighted that possible punishments influence patients' behaviours
      more than possible rewards. Significant correlations between delay aversion
      scores on the CGT and QDQ delay aversion subscale suggest that these two
      instruments can be used in synergy to reach a convergent validity. In conclusion,
      our results show that not all impulsivities are detrimentally affected by DBS of
      the STN and that the joint use of experimental paradigms and psychological
      questionnaires can provide useful insights in the study of impulsivity.

PMID- 22984416
TI  - Night-migratory songbirds possess a magnetic compass in both eyes.
AB  - Previous studies on European robins, Erithacus rubecula, and Australian
      silvereyes, Zosterops lateralis, had suggested that magnetic compass information
      is being processed only in the right eye and left brain hemisphere of migratory
      birds. However, recently it was demonstrated that both garden warblers, Sylvia
      borin, and European robins have a magnetic compass in both eyes. These results
      raise the question if the strong lateralization effect observed in earlier
      experiments might have arisen from artifacts or from differences in experimental
      conditions rather than reflecting a true all-or-none lateralization of the
      magnetic compass in European robins. Here we show that (1) European robins having
      only their left eye open can orient in their seasonally appropriate direction
      both during autumn and spring, i.e. there are no strong lateralization
      differences between the outward journey and the way home, that (2) their
      directional choices are based on the standard inclination compass as they are
      turned 180 degrees  when the inclination is reversed, and that (3) the capability
      to use the magnetic compass does not depend on monocular learning or intraocular
      transfer as it is already present in the first tests of the birds with only one
      eye open.

PMID- 22984417
TI  - Desynchronisation of glycolytic oscillations in yeast cell populations.
AB  - Glycolytic oscillations of intact yeast cells of the strain Saccharomyces
      carlsbergensis were investigated at both the levels of cell populations and of
      individual cells. Individual cells showed glycolytic oscillations even at very
      low cell densities (e.g. 1.0 x 10(5) cells/ml). By contrast, the collective
      behaviour on the population level was cell density-dependent: at high cell
      densities it is oscillatory, but below the threshold density of 1.0 x 10(6)
      cells/ml the collective dynamics becomes quiescent. We demonstrate that the
      transition in the collective dynamics is caused by the desynchronisation of the
      oscillations of individual cells. This is characteristic for a Kuramoto
      transition. Spatially resolved measurements at low cell densities revealed that
      even cells that adhere to their neighbours oscillated with their own, independent
      frequencies and phases.

PMID- 22984418
TI  - Intracellular context affects levels of a chemically dependent destabilizing
      domain.
AB  - The ability to regulate protein levels in live cells is crucial to understanding
      protein function. In the interest of advancing the tool set for protein
      perturbation, we developed a protein destabilizing domain (DD) that can confer
      its instability to a fused protein of interest. This destabilization and
      consequent degradation can be rescued in a reversible and dose-dependent manner
      with the addition of a small molecule that is specific for the DD, Shield-1.
      Proteins encounter different local protein quality control (QC) machinery when
      targeted to cellular compartments such as the mitochondrial matrix or endoplasmic
      reticulum (ER). These varied environments could have profound effects on the
      levels and regulation of the cytoplasmically derived DD. Here we show that DD
      fusions in the cytoplasm or nucleus can be efficiently degraded in mammalian
      cells; however, targeting fusions to the mitochondrial matrix or ER lumen leads
      to accumulation even in the absence of Shield-1. Additionally, we characterize
      the behavior of the DD with perturbants that modulate protein production,
      degradation, and local protein QC machinery. Chemical induction of the unfolded
      protein response in the ER results in decreased levels of an ER-targeted DD
      indicating the sensitivity of the DD to the degradation environment. These data
      reinforce that DD is an effective tool for protein perturbation, show that the
      local QC machinery affects levels of the DD, and suggest that the DD may be a
      useful probe for monitoring protein quality control machinery.

PMID- 22984419
TI  - Non-covalent interaction between polyubiquitin and GTP cyclohydrolase 1 dictates
      its degradation.
AB  - GTP cyclohydrolase 1 (GTPCH1) is the rate-limiting enzyme in the de novo
      synthesis of tetrahydrobiopterin (BH4). GTPCH1 protein degradation has been
      reported in animal models of several diseases, including diabetes mellitus and
      hypertension. However, the molecular mechanisms by which GTPCH1 is degraded
      remain uncharacterized. Here we report a novel non-covalent interaction between
      polyubiquitin and GTPCH1 in vitro and in vivo. The non-covalent binding of GTPCH1
      to polyubiquitin via an ubiquitin-binding domain (UBD) results in ubiquitination
      and degradation. Ectopic expression of ubiquitin in cultured cells accelerated
      GTPCH1 degradation. In cultured cells and in vitro assays, Lys48-linked ubiquitin
      chains, but not Lys63-linked chains, interacted with GTPCH1 and targeted it for
      degradation. Consistently, proteasome inhibition attenuated GTPCH1 degradation.
      Finally, direct mutagenesis of an isoleucine (Ile131) in the hydrophobic patch of
      the GTPCH1 UBD affected its ubiquitin binding and the enzyme stability. Taken
      together, we conclude that GTPCH1 non-covalently interacts with polyubiquitin via
      an ubiquitin-binding domain. The polyubiquitin binding directs GTPCH1
      ubiquitination and proteasome degradation.

PMID- 22984420
TI  - Agonistic and antagonistic roles for TNIK and MINK in non-canonical and canonical
      Wnt signalling.
AB  - Wnt signalling is a key regulatory factor in animal development and homeostasis
      and plays an important role in the establishment and progression of cancer. Wnt
      signals are predominantly transduced via the Frizzled family of serpentine
      receptors to two distinct pathways, the canonical beta-catenin pathway and a non
      canonical pathway controlling planar cell polarity and convergent extension.
      Interference between these pathways is an important determinant of cellular and
      phenotypic responses, but is poorly understood. Here we show that TNIK (Traf2 and
      Nck-interacting kinase) and MINK (Misshapen/NIKs-related kinase) MAP4K signalling
      kinases are integral components of both canonical and non-canonical pathways in
      Xenopus. xTNIK and xMINK interact and are proteolytically cleaved in vivo to
      generate Kinase domain fragments that are active in signal transduction, and
      Citron-NIK-Homology (CNH) Domain fragments that are suppressive. The catalytic
      activity of the Kinase domain fragments of both xTNIK and xMINK mediate non
      canonical signalling. However, while the Kinase domain fragments of xTNIK also
      mediate canonical signalling, the analogous fragments derived from xMINK strongly
      antagonize this signalling. Our data suggest that the proteolytic cleavage of
      xTNIK and xMINK determines their respective activities and is an important factor
      in controlling the balance between canonical and non-canonical Wnt signalling in
      vivo.

PMID- 22984421
TI  - Effects of dominance and diversity on productivity along Ellenberg's experimental
      water table gradients.
AB  - Heinz Ellenberg's historically important work on changes in the abundances of a
      community of grass species growing along experimental gradients of water table
      depth has played an important role in helping to identify the hydrological niches
      of plant species in wet meadows. We present a previously unpublished complete
      version of Ellenberg's dataset from the 1950s together with the results of a
      series of modern statistical analyses testing for hypothesized overyielding of
      aboveground net primary production as a consequence of resource-based niche
      differentiation. Interactions of species with water table depth and soil type in
      the results of our analyses are qualitatively consistent with earlier
      interpretations of evidence for differences in the fundamental and realized
      niches of species. Arrhenatherum elatius tended to dominate communities and this
      effect was generally positively related to increasing water table depth. There
      was little overyielding of aboveground net primary production during the two
      repeats of the experiment conducted in successive single growing seasons.
      Examination of how the effects of biodiversity on ecosystem processes vary across
      environmental gradients is an underutilized approach--particularly where the
      gradient is thought to be an axis of niche differentiation as is the case with
      water availability. Furthermore, advances in ecology and statistics during the 60
      years since Ellenberg's classic experiment was performed suggest that it may be
      worth repeating over a longer duration and with modern experimental design and
      methodologies.

PMID- 22984422
TI  - Global genome analysis of the downstream binding targets of testis determining
      factor SRY and SOX9.
AB  - A major event in mammalian male sex determination is the induction of the testis
      determining factor Sry and its downstream gene Sox9. The current study provides
      one of the first genome wide analyses of the downstream gene binding targets for
      SRY and SOX9 to help elucidate the molecular control of Sertoli cell
      differentiation and testis development. A modified ChIP-Chip analysis using a
      comparative hybridization was used to identify 71 direct downstream binding
      targets for SRY and 109 binding targets for SOX9. Interestingly, only 5 gene
      targets overlapped between SRY and SOX9. In addition to the direct response
      element binding gene targets, a large number of atypical binding gene targets
      were identified for both SRY and SOX9. Bioinformatic analysis of the downstream
      binding targets identified gene networks and cellular pathways potentially
      involved in the induction of Sertoli cell differentiation and testis development.
      The specific DNA sequence binding site motifs for both SRY and SOX9 were
      identified. Observations provide insights into the molecular control of male
      gonadal sex determination.

PMID- 22984423
TI  - Interaction between alcohol consumption and CYP 2C19 gene polymorphism in
      relation to oesophageal squamous cell carcinoma.
AB  - OBJECTIVES: The purpose of this study is to explore the relationship between the
      interactions of CYP2C19 gene polymorphisms and several environmental factors and
      oesophageal squamous cell carcinoma (OSCC). METHODS: In a case-control study of
      OSCC patients (n = 350) and healthy controls (n = 350), we investigated the roles
      of polymorphism in the CYP2C19 gene by the use of polymerase chain reaction-
      restriction fragment length polymorphism (PCR - RFLP) analysis. RESULTS: The
      CYP2C19(*)3 AG+AA genotype was significantly more prevalent in OSCC patients
      (10.0% versus 3.43%; P<0.01). Multiple logistic regression analysis showed
      drinking (OR: 5.603, 95% CI: 3.431-11.112; P = 0.005) and smoking (OR: 4.341, 95%
      CI: 3.425-10.241; P = 0.001) was the independent risk factor of OSCC
      respectively, and there were significant interaction between CYP2C19(*)3 and
      drinking (OR: 8.747, 95% CI: 6.321-18.122; P = 0.009). CONCLUSIONS: The
      CYP2C19(*)3 polymorphism and OSCC were synergistically and significantly
      associated in Chinese Han patients.

PMID- 22984424
TI  - Both baseline clinical factors and genetic polymorphisms influence the
      development of severe functional status in ankylosing spondylitis.
AB  - Functional severity in ankylosing spondylitis (AS) patients is variable and
      difficult to predict early. The aim of our study was to assess whether a
      combination of baseline clinical factors and genetic markers may predict the
      development of severe functional status in AS. We performed a cross-sectional
      association study on AS patients included in the Spanish National Registry of
      Spondyloarthropathies--REGISPONSER. Bath Ankylosing Spondylitis Functional Index
      (BASFI) was standardized by adjusting for disease duration since the first
      symptoms (BASFI/t). We considered as severe functional status the values of
      BASFI/t in the top of the 60th (p60), 65th (p65), 70th (p70), and 75th (p75)
      percentile. We selected 384 single nucleotide polymorphisms (SNPs) distributed in
      190 genes to be analyzed. The study cohort included 456 patients with mean age
      50.8(+/- 10.5) years and with mean disease duration since first symptoms 24.7 (+/
      10.1) years. Older age at disease onset and neck pain at baseline showed
      statistical significant association with severe BASFI/t. Polymorphisms associated
      in the allele frequencies test with severe BASFI/t in all classifications were:
      rs2542151 (p60 [P = .04], p65 [P = .04], p70 [P = .001] and p75 [P = .001]) and
      rs2254441 (p60 [P = .004], p65 [P = .02], p70 [P = .01] and p75 [P<.001])..
      Genotype association, after adjustment for covariates, found an association in
      three of the four patients' classifications for rs2542151 and in two of the
      classifications for rs2254441.Forward logistic regression did not identify any
      model with a good predictive power for severe functional development.In our study
      we identified clinical factors and 24 polymorphisms associated with development
      of severe functional status in AS patients. Validation of these results in other
      cohorts is required.

PMID- 22984425
TI  - Consistent implementation of decisions in the brain.
AB  - Despite the complexity and variability of decision processes, motor responses are
      generally stereotypical and independent of decision difficulty. How is this
      consistency achieved? Through an engineering analogy we consider how and why a
      system should be designed to realise not only flexible decision-making, but also
      consistent decision implementation. We specifically consider neurobiologically
      plausible accumulator models of decision-making, in which decisions are made when
      a decision threshold is reached. To trade-off between the speed and accuracy of
      the decision in these models, one can either adjust the thresholds themselves or,
      equivalently, fix the thresholds and adjust baseline activation. Here we review
      how this equivalence can be implemented in such models. We then argue that
      manipulating baseline activation is preferable as it realises consistent decision
      implementation by ensuring consistency of motor inputs, summarise empirical
      evidence in support of this hypothesis, and suggest that it could be a general
      principle of decision making and implementation. Our goal is therefore to review
      how neurobiologically-plausible models of decision-making can manipulate speed
      accuracy trade-offs using different mechanisms, to consider which of these
      mechanisms has more desirable decision-implementation properties, and then review
      the relevant neuroscientific data on which mechanism brains actually use.

PMID- 22984426
TI  - Unlike pancreatic cancer cells pancreatic cancer associated fibroblasts display
      minimal gene induction after 5-aza-2'-deoxycytidine.
AB  - PURPOSE: Cancer associated stromal fibroblasts (CAFs) undergo transcriptional and
      phenotypic changes that contribute to tumor progression, but the mechanisms
      responsible for these changes are not well understood. Aberrant DNA methylation
      is an important cause of transcriptional alterations in cancer cells but it is
      not known how important DNA methylation alterations are to CAF behavior.
      EXPERIMENTAL DESIGN: We used Affymetrix exon arrays to compare genes induced by
      the DNA methylation inhibitor 5-aza-dC in cultured pancreatic cancer associated
      fibroblasts, pancreatic control fibroblasts and pancreatic cancer cell lines.
      RESULTS: We found that pancreatic CAFs and control pancreatic fibroblasts were
      less responsive to 5-aza-dC-mediated gene reactivation than pancreatic cancer
      cells (mean+/-SD of genes induced >= 5-fold was 9 +/- 10 genes in 10 pancreatic
      CAF cultures, 17 +/- 14 genes in 3 control pancreatic fibroblast cultures, and
      134 +/- 85 genes in 4 pancreatic cancer cell lines). We examined differentially
      expressed genes between CAFs and control fibroblasts for candidate methylated
      genes and identified the disintegrin and metalloprotease, ADAM12 as
      hypomethylated and overexpressed in pancreatic CAF lines and overexpressed in
      fibroblasts adjacent to primary pancreatic adenocarcinomas. CONCLUSIONS: Compared
      to pancreatic cancer cells, few genes are reactivated by DNMT1 inhibition in
      pancreatic CAFs suggesting these cells do not harbor many functionally important
      alterations in DNA methylation. CAFs may also not be very responsive to
      therapeutic targeting with DNA methylation inhibitors.

PMID- 22984427
TI  - Clinical utility of insulin-like growth factor 1 and 2; determination by high
      resolution mass spectrometry.
AB  - Measurement of insulin-like growth factor-1 (IGF-I) has utility for the diagnosis
      and management of growth disorders, but inter-assay comparison of results has
      been complicated by a multitude of reference standards, antibodies, detection
      methods, and pre-analytical preparation strategies. We developed a quantitative
      LC-MS method for intact IGF-I, which has advantages in throughput and complexity
      when compared to mass spectrometric approaches that rely on stable isotope
      dilution analysis of tryptic peptides. Since the method makes use of full-scan
      data, the assay was easily extended to provide quantitative measurement of IGF-II
      using the same assay protocol. The validated LC-MS assay for IGF-I and IGF-II
      provides accurate results across the pediatric and adult reference range and is
      suitable for clinical use.

PMID- 22984428
TI  - Multiphoton multispectral fluorescence lifetime tomography for the evaluation of
      basal cell carcinomas.
AB  - We present the first detailed study using multispectral multiphoton fluorescence
      lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal
      keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples
      of normal skin (in & ex vivo). Features from fluorescence lifetime images were
      used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively.
      A mosaic of BCC fluorescence lifetime images covering >1 mm(2) is also presented,
      demonstrating the potential for tumour margin delineation. Using 10,462 manually
      segmented cells from the image data, we quantify the cellular morphology and
      spectroscopic differences between BCCs and normal skin for the first time.
      Statistically significant increases were found in the fluorescence lifetimes of
      cells from BCCs in all spectral channels, ranging from 19.9% (425-515 nm spectral
      emission) to 39.8% (620-655 nm emission). A discriminant analysis based
      diagnostic algorithm allowed the fraction of cells classified as malignant to be
      calculated for each patient. This yielded a receiver operator characteristic area
      under the curve for the detection of BCC of 0.83. We have used both morphological
      and spectroscopic parameters to discriminate BCC from normal skin, and provide a
      comprehensive base for how this technique could be used for BCC assessment in
      clinical practice.

PMID- 22984429
TI  - Association of shank 1A scaffolding protein with cone photoreceptor terminals in
      the mammalian retina.
AB  - Photoreceptor terminals contain post-synaptic density (PSD) proteins e.g., PSD
      95/PSD-93, but their role at photoreceptor synapses is not known. PSDs are
      generally restricted to post-synaptic boutons in central neurons and form
      scaffolding with multiple proteins that have structural and functional roles in
      neuronal signaling. The Shank family of proteins (Shank 1-3) functions as
      putative anchoring proteins for PSDs and is involved in the organization of
      cytoskeletal/signaling complexes in neurons. Specifically, Shank 1 is restricted
      to neurons and interacts with both receptors and signaling molecules at central
      neurons to regulate plasticity. However, it is not known whether Shank 1 is
      expressed at photoreceptor terminals. In this study we have investigated Shank 1A
      localization in the outer retina at photoreceptor terminals. We find that Shank
      1A is expressed presynaptically in cone pedicles, but not rod spherules, and it
      is absent from mice in which the Shank 1 gene is deleted. Shank 1A co-localizes
      with PSD-95, peanut agglutinin, a marker of cone terminals, and glycogen
      phosphorylase, a cone specific marker. These findings provide convincing evidence
      for Shank 1A expression in both the inner and outer plexiform layers, and
      indicate a potential role for PSD-95/Shank 1 complexes at cone synapses in the
      outer retina.

PMID- 22984430
TI  - Sirtuin 1 regulates SREBP-1c expression in a LXR-dependent manner in skeletal
      muscle.
AB  - Sirtuin 1 (SIRT1), a NAD(+)-dependent protein deacetylase, has emerged as a main
      determinant of whole body homeostasis in mammals by regulating a large spectrum
      of transcriptional regulators in metabolically relevant tissue such as liver,
      adipose tissue and skeletal muscle. Sterol regulatory element binding protein
      (SREBP)-1c is a transcription factor that controls the expression of genes
      related to fatty acid and triglyceride synthesis in tissues with high lipid
      synthesis rates such as adipose tissue and liver. Previous studies indicate that
      SIRT1 can regulate the expression and function of SREBP-1c in liver. In the
      present study, we determined whether SIRT1 regulates SREBP-1c expression in
      skeletal muscle. SREBP-1c mRNA and protein levels were decreased in the
      gastrocnemius muscle of mice harboring deletion of the catalytic domain of SIRT1
      (SIRT1(Deltaex4/Deltaex4) mice). By contrast, adenoviral expression of SIRT1 in
      human myotubes increased SREBP-1c mRNA and protein levels. Importantly, SREBP-1c
      promoter transactivation, which was significantly increased in response to SIRT1
      overexpression by gene electrotransfer in skeletal muscle, was completely
      abolished when liver X receptor (LXR) response elements were deleted. Finally,
      our in vivo data from SIRT1(Deltaex4/Deltaex4) mice and in vitro data from human
      myotubes overexpressing SIRT1 show that SIRT1 regulates LXR acetylation in
      skeletal muscle cells. This suggests a possible mechanism by which the regulation
      of SREBP-1c gene expression by SIRT1 may require the deacetylation of LXR
      transcription factors.

PMID- 22984431
TI  - Supply of neuraminidase inhibitors related to reduced influenza A (H1N1)
      mortality during the 2009-2010 H1N1 pandemic: an ecological study.
AB  - BACKGROUND: The influenza A (H1N1) pandemic swept across the globe from April
      2009 to August 2010 affecting millions. Many WHO Member States relied on
      antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and
      zanamivir, to treat influenza patients in critical condition. Such drugs have
      been found to be effective in reducing severity and duration of influenza
      illness, and likely reduced morbidity during the pandemic. However, it is less
      clear whether NAIs used during the pandemic reduced H1N1 mortality. METHODS:
      Country-level data on supply of oseltamivir and zanamivir were used to predict
      H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two
      WHO Member States. Poisson regression was used to model the association between
      NAI supply and H1N1 mortality, with adjustment for economic, demographic, and
      health-related confounders. RESULTS: After adjustment for potential confounders,
      each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated
      with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate
      (RR) = 0.84 per log increase in oseltamivir supply). While the supply of
      zanamivir was considerably less than that of oseltamivir in each Member State,
      each 10% increase in kilogram of active zanamivir, per 100,000, was associated
      with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). CONCLUSION:
      While there are limitations to the ecologic nature of these data, this analysis
      offers evidence of a protective relationship between antiviral drug supply and
      influenza mortality and supports a role for influenza antiviral use in future
      pandemics.

PMID- 22984432
TI  - Dynamics of ceramide channels detected using a microfluidic system.
AB  - Ceramide, a proapoptotic sphingolipid, has been shown to form channels, in
      mitochondrial outer membranes, large enough to translocate proteins. In
      phospholipid membranes, electrophysiological studies and electron microscopic
      visualization both report that these channels form in a range of sizes with a
      modal value of 10 nm in diameter. A hydrogen bonded barrel-like structure
      consisting of hundreds of ceramide molecules has been proposed for the structure
      of the channel and this is supported by electrophysiological studies and
      molecular dynamic simulations. To our knowledge, the mechanical strength and
      deformability of such a large diameter but extremely thin cylindrical structure
      has never been reported. Here we present evidence for a reversible mechanical
      distortion of the cylinder following the addition of La(3+). A microfluidic
      system was used to repeatedly lower and then restore the conductance by
      alternatively perfusing La(3+) and EDTA. Although aspects of the kinetics of
      conductance drop and recovery are consistent with a
      disassembly/diffusion/reassembly model, others are inconsistent with the expected
      time scale of lateral diffusion of disassembled channel fragments in the
      membrane. The presence of a residual conductance following La(3+) treatment and
      the relationship between the residual conductance and the initial conductance
      were both indicative of a distortion/recovery process in analogy with a pressure
      induced distortion of a flexible cylinder.

PMID- 22984433
TI  - The hidden geometries of the Arabidopsis thaliana epidermis.
AB  - The quest for the discovery of mathematical principles that underlie biological
      phenomena is ancient and ongoing. We present a geometric analysis of the complex
      interdigitated pavement cells in the Arabidopsis thaliana (Col.) adaxial
      epidermis with a view to discovering some geometric characteristics that may
      govern the formation of this tissue. More than 2,400 pavement cells from 10, 17
      and 24 day old leaves were analyzed. These interdigitated cells revealed a number
      of geometric properties that remained constant across the three age groups. In
      particular, the number of digits per cell rarely exceeded 15, irrespective of
      cell area. Digit numbers per 100 um(2) cell area reduce with age and as cell area
      increases, suggesting early developmental programming of digits. Cell shape
      proportions as defined by length:width ratios were highly conserved over time
      independent of the size and, interestingly, both the mean and the medians were
      close to the golden ratio 1.618034. With maturity, the cell area:perimeter ratios
      increased from a mean of 2.0 to 2.4. Shape properties as defined by the medial
      axis transform (MAT) were calculated and revealed that branch points along the
      MAT typically comprise one large and two small angles. These showed consistency
      across the developmental stages considered here at 140 degrees  (+/- 5 degrees )
      for the largest angles and 110 degrees  (+/- 5 degrees ) for the smaller angles.
      Voronoi diagram analyses of stomatal center coordinates revealed that giant
      pavement cells (>= 500 um(2)) tend to be arranged along Voronoi boundaries
      suggesting that they could function as a scaffold of the epidermis. In addition,
      we propose that pavement cells have a role in spacing and positioning of the
      stomata in the growing leaf and that they do so by growing within the limits of a
      set of 'geometrical rules'.

PMID- 22984434
TI  - Integrating various resources for gene name normalization.
AB  - The recognition and normalization of gene mentions in biomedical literature are
      crucial steps in biomedical text mining. We present a system for extracting gene
      names from biomedical literature and normalizing them to gene identifiers in
      databases. The system consists of four major components: gene name recognition,
      entity mapping, disambiguation and filtering. The first component is a gene name
      recognizer based on dictionary matching and semi-supervised learning, which
      utilizes the co-occurrence information of a large amount of unlabeled MEDLINE
      abstracts to enhance feature representation of gene named entities. In the stage
      of entity mapping, we combine the strategies of exact match and approximate match
      to establish linkage between gene names in the context and the EntrezGene
      database. For the gene names that map to more than one database identifiers, we
      develop a disambiguation method based on semantic similarity derived from the
      Gene Ontology and MEDLINE abstracts. To remove the noise produced in the previous
      steps, we design a filtering method based on the confidence scores in the
      dictionary used for NER. The system is able to adjust the trade-off between
      precision and recall based on the result of filtering. It achieves an F-measure
      of 83% (precision: 82.5% recall: 83.5%) on BioCreative II Gene Normalization (GN)
      dataset, which is comparable to the current state-of-the-art.

PMID- 22984435
TI  - Dendritic cells control CD4+CD25+ Treg cell suppressor function in vitro through
      juxtacrine delivery of IL-2.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) restrict inflammatory responses
      to self and nonself. Aberrant Treg activity is pathologic: Insufficient Treg
      activity is implicated in autoimmunity, allergy, and graft-versus-host-disease;
      overabundant activity is implicated in chronic infection and cancer. Tregs
      require IL-2 for their expansion and acquisition/execution of suppressor
      function; however, because Tregs cannot produce IL-2, they depend on IL-2 from an
      exogenous source. Until now, that IL-2 source had not been established. We asked
      whether dendritic cells (DCs) could supply IL-2 to Tregs and, if so, what was
      required for that delivery. We used flow cytometry, IL-2 ELISPOT, RT-qPCR, and IL
      2 promoter-driven reporter assays to measure intracytoplasmic IL-2, secreted
      protein, IL-2 message and IL-2 promoter activity in bone marrow-derived (BMDC)
      and splenic DCs. We examined conjugate formation between Tregs, conventional
      CD4(+) cells, and IL-2-expressing DCs. We measured Treg levels of CD25, Foxp3,
      and suppressor function after co-culture with IL-2 sufficient and IL-2(-/-) DCs.
      We generated IL-2-mCherry-expressing DCs and used epifluorescence microscopy and
      flow cytometry to track IL-2 transfer to Tregs and test requirements for
      transfer. Between 0.7 to 2.4% of DCs constitutively produced IL-2 and diverted IL
      2 secretion to Tregs by preferentially forming conjugates with them. Uptake of DC
      IL-2 by Tregs required cell-cell contact and CD25. Tregs increased levels of CD25
      and Foxp3 from baseline and showed greater suppressor function when co-cultured
      with IL-2-sufficient DCs, but not when co-cultured with IL-2(-/-) DCs. Exogenous
      IL-2, added in excess of 500 U/ml to co-cultures with IL-2(-/-) DCs, restored
      Treg suppressor function. These data support a model of juxtacrine delivery of IL
      2 from DCs to Tregs and suggest that a subset of DCs modulates Treg function
      through controlled, spatial delivery of IL-2. Knowledge of how DCs regulate Tregs
      should be integrated into the design of interventions intended to alter Treg
      function.

PMID- 22984436
TI  - Stream segregation in the perception of sinusoidally amplitude-modulated tones.
AB  - Amplitude modulation can serve as a cue for segregating streams of sounds from
      different sources. Here we evaluate stream segregation in humans using ABA-
      sequences of sinusoidally amplitude modulated (SAM) tones. A and B represent SAM
      tones with the same carrier frequency (1000, 4000 Hz) and modulation depth (30,
      100%). The modulation frequency of the A signals (f(modA)) was 30, 100 or 300 Hz,
      respectively. The modulation frequency of the B signals was up to four octaves
      higher (Deltaf(mod)). Three different ABA- tone patterns varying in tone duration
      and stimulus onset asynchrony were presented to evaluate the effect of forward
      suppression. Subjects indicated their 1- or 2-stream percept on a touch screen at
      the end of each ABA- sequence (presentation time 5 or 15 s). Tone pattern,
      f(modA), Deltaf(mod), carrier frequency, modulation depth and presentation time
      significantly affected the percentage of a 2-stream percept. The human
      psychophysical results are compared to responses of avian forebrain neurons
      evoked by different ABA- SAM tone conditions [1] that were broadly overlapping
      those of the present study. The neurons also showed significant effects of tone
      pattern and Deltaf(mod) that were comparable to effects observed in the present
      psychophysical study. Depending on the carrier frequency, modulation frequency,
      modulation depth and the width of the auditory filters, SAM tones may provide
      mainly temporal cues (sidebands fall within the range of the filter), spectral
      cues (sidebands fall outside the range of the filter) or possibly both. A
      computational model based on excitation pattern differences was used to predict
      the 50% threshold of 2-stream responses. In conditions for which the model
      predicts a considerably larger 50% threshold of 2-stream responses (i.e., larger
      Deltaf(mod) at threshold) than was observed, it is unlikely that spectral cues
      can provide an explanation of stream segregation by SAM.

PMID- 22984437
TI  - Site specific cleavage mediated by MMPs regulates function of agrin.
AB  - BACKGROUND: Agrin is the key inducer of postsynaptic differentiations at the
      neuromuscular junction. The multidomain heparan sulfate proteoglycan is mediating
      via its N-terminal segment the interaction with laminin, whereas the C-terminal
      portion is responsible for Dystroglycan binding and clustering of the
      Acetylcholine receptor. Matrix metalloproteinases (MMP) are known to play
      essential roles in matrix remodeling, degradation and regulation of extracellular
      signaling networks. PRINCIPAL FINDINGS: Site-specific processing of Agrin
      provides key insight into regulatory effects of Matrix metalloproteinases (MMPs).
      Here, we present a detailed study of agrin processing by different MMPs together
      with a molecular understanding of binding and cleavage at both terminal
      fragments. The data suggest for a regulatory effect of MMP cleavage at
      particularly important functional sites of agrin. Cleave of agrin abolishes the
      agrin-laminin complex formation and the Acetylcholine receptor clustering at the
      neuromuscular junction. CONCLUSION/SIGNIFICANCE: Agrin is a target of specific
      MMP processing resulting in agrin subfragments with different regulatory
      activities. MMP processing is a powerful tool to regulate extracellular signaling
      networks.

PMID- 22984438
TI  - An economical method for production of (2)H, (13)CH3-threonine for solution NMR
      studies of large protein complexes: application to the 670 kDa proteasome.
AB  - NMR studies of very high molecular weight protein complexes have been greatly
      facilitated through the development of labeling strategies whereby (13)CH(3)
      methyl groups are introduced into highly deuterated proteins. Robust and cost
      effective labeling methods are well established for all methyl containing amino
      acids with the exception of Thr. Here we describe an inexpensive biosynthetic
      strategy for the production of L-[alpha-(2)H; beta-(2)H;gamma-(13)C]-Thr that can
      then be directly added during protein expression to produce highly deuterated
      proteins with Thr methyl group probes of structure and dynamics. These reporters
      are particularly valuable, because unlike other methyl containing amino acids,
      Thr residues are localized predominantly to the surfaces of proteins, have unique
      hydrogen bonding capabilities, have a higher propensity to be found at protein
      nucleic acid interfaces and can play important roles in signaling pathways
      through phosphorylation. The utility of the labeling methodology is demonstrated
      with an application to the 670 kDa proteasome core particle, where high quality
      Thr (13)C,(1)H correlation spectra are obtained that could not be generated from
      samples prepared with commercially available U-[(13)C,(1)H]-Thr.

PMID- 22984440
TI  - Tourism and the conservation of critically endangered frogs.
AB  - Protected areas are critical for the conservation of many threatened species.
      Despite this, many protected areas are acutely underfunded, which reduces their
      effectiveness significantly. Tourism is one mechanism to promote and fund
      conservation in protected areas, but there are few studies analyzing its tangible
      conservation outcomes for threatened species. This study uses the 415 IUCN
      critically endangered frog species to evaluate the contribution of protected area
      tourism revenue to conservation. Contributions were calculated for each species
      as the proportion of geographic range inside protected areas multiplied by the
      proportion of protected area revenues derived from tourism. Geographic ranges
      were determined from IUCN Extent of Occurrence maps. Almost 60% (239) of
      critically endangered frog species occur in protected areas. Higher proportions
      of total range are protected in Nearctic, Australasian and Afrotopical regions.
      Tourism contributions to protected area budgets ranged from 5-100%. These
      financial contributions are highest for developing countries in the Afrotropical,
      Indomalayan and Neotropical regions. Data for both geographic range and budget
      are available for 201 critically endangered frog species with proportional
      contributions from tourism to species protection ranging from 0.8-99%. Tourism's
      financial contributions to critically endangered frog species protection are
      highest in the Afrotropical region. This study uses a coarse measure but at the
      global scale it demonstrates that tourism has significant potential to contribute
      to global frog conservation efforts.

PMID- 22984439
TI  - delta-Catenin is genetically and biologically associated with cortical cataract
      and future Alzheimer-related structural and functional brain changes.
AB  - Multiple lines of evidence suggest that specific subtypes of age-related cataract
      (ARC) and Alzheimer disease (AD) are related etiologically. To identify shared
      genetic factors for ARC and AD, we estimated co-heritability of quantitative
      measures of cataract subtypes with AD-related brain MRI traits among 1,249
      members of the Framingham Eye Study who had a brain MRI scan approximately ten
      years after the eye exam. Cortical cataract (CC) was found to be co-heritable
      with future development of AD and with several MRI traits, especially temporal
      horn volume (THV, rho = 0.24, P<10(-4)). A genome-wide association study using
      187,657 single nucleotide polymorphisms (SNPs) for the bivariate outcome of CC
      and THV identified genome-wide significant association with CTNND2 SNPs
      rs17183619, rs13155993 and rs13170756 (P<2.6 * 10(-7)). These SNPs were also
      significantly associated with bivariate outcomes of CC and scores on several
      highly heritable neuropsychological tests (5.7 * 10(-9) <= P<3.7 * 10(-6)).
      Statistical interaction was demonstrated between rs17183619 and APP SNP rs2096488
      on CC (P = 0.0015) and CC-THV (P = 0.038). A rare CTNND2 missense mutation
      (G810R) 249 base pairs from rs17183619 altered delta-catenin localization and
      increased secreted amyloid-beta(1-42) in neuronal cell culture.
      Immunohistopathological analysis of lens tissue obtained from two autopsy
      confirmed AD subjects and two non-AD controls revealed elevated expression of
      delta-catenin in epithelial and cortical regions of lenses from AD subjects
      compared to controls. Our findings suggest that genetic variation in delta
      catenin may underlie both cortical lens opacities in mid-life and subsequent MRI
      and cognitive changes that presage the development of AD.

PMID- 22984441
TI  - An overview of the genetic structure within the Italian population from genome
      wide data.
AB  - In spite of the common belief of Europe as reasonably homogeneous at genetic
      level, advances in high-throughput genotyping technology have resolved several
      gradients which define different geographical areas with good precision. When
      Northern and Southern European groups were considered separately, there were
      clear genetic distinctions. Intra-country genetic differences were also evident,
      especially in Finland and, to a lesser extent, within other European populations.
      Here, we present the first analysis using the 125,799 genome-wide Single
      Nucleotide Polymorphisms (SNPs) data of 1,014 Italians with wide geographical
      coverage. We showed by using Principal Component analysis and model-based
      individual ancestry analysis, that the current population of Sardinia can be
      clearly differentiated genetically from mainland Italy and Sicily, and that a
      certain degree of genetic differentiation is detectable within the current
      Italian peninsula population. Pair-wise F(ST) statistics Northern and Southern
      Italy amounts approximately to 0.001 between, and around 0.002 between Northern
      Italy and Utah residents with Northern and Western European ancestry (CEU). The
      Italian population also revealed a fine genetic substructure underscoring by the
      genomic inflation (Sardinia vs. Northern Italy = 3.040 and Northern Italy vs. CEU
      = 1.427), warning against confounding effects of hidden relatedness and
      population substructure in association studies.

PMID- 22984442
TI  - Structure of a novel winged-helix like domain from human NFRKB protein.
AB  - The human nuclear factor related to kappa-B-binding protein (NFRKB) is a 1299
      residue protein that is a component of the metazoan INO80 complex involved in
      chromatin remodeling, transcription regulation, DNA replication and DNA repair.
      Although full length NFRKB is predicted to be around 65% disordered, comparative
      sequence analysis identified several potentially structured sections in the N
      terminal region of the protein. These regions were targeted for crystallographic
      studies, and the structure of one of these regions spanning residues 370-495 was
      determined using the JCSG high-throughput structure determination pipeline. The
      structure reveals a novel, mostly helical domain reminiscent of the winged-helix
      fold typically involved in DNA binding. However, further analysis shows that this
      domain does not bind DNA, suggesting it may belong to a small group of winged
      helix domains involved in protein-protein interactions.

PMID- 22984443
TI  - A detailed, hierarchical study of Giardia lamblia's ventral disc reveals novel
      microtubule-associated protein complexes.
AB  - Giardia lamblia is a flagellated, unicellular parasite of mammals infecting over
      one billion people worldwide. Giardia's two-stage life cycle includes a motile
      trophozoite stage that colonizes the host small intestine and an infectious cyst
      form that can persist in the environment. Similar to many eukaryotic cells,
      Giardia contains several complex microtubule arrays that are involved in
      motility, chromosome segregation, organelle transport, maintenance of cell shape
      and transformation between the two life cycle stages. Giardia trophozoites also
      possess a unique spiral microtubule array, the ventral disc, made of
      approximately 50 parallel microtubules and associated microribbons, as well as a
      variety of associated proteins. The ventral disc maintains trophozoite attachment
      to the host intestinal epithelium. With the help of a combined SEM/microtome
      based slice and view method called 3View(r) (Gatan Inc., Pleasanton, CA), we
      present an entire trophozoite cell reconstruction and describe the arrangement of
      the major cytoskeletal elements. To aid in future analyses of disc-mediated
      attachment, we used electron-tomography of freeze-substituted, plastic-embedded
      trophozoites to explore the detailed architecture of ventral disc microtubules
      and their associated components. Lastly, we examined the disc microtubule array
      in three dimensions in unprecedented detail using cryo-electron tomography
      combined with internal sub-tomogram volume averaging of repetitive domains. We
      discovered details of protein complexes stabilizing microtubules by attachment to
      their inner and outer wall. A unique tri-laminar microribbon structure is
      attached vertically to the disc microtubules and is connected to neighboring
      microribbons via crossbridges. This work provides novel insight into the
      structure of the ventral disc microtubules, microribbons and associated proteins.
      Knowledge of the components comprising these structures and their three
      dimensional organization is crucial toward understanding how attachment via the
      ventral disc occurs in vivo.

PMID- 22984444
TI  - Evolutionary conservation of the ribosomal biogenesis factor Rbm19/Mrd1:
      implications for function.
AB  - Ribosome biogenesis in eukaryotes requires coordinated folding and assembly of a
      pre-rRNA into sequential pre-rRNA-protein complexes in which chemical
      modifications and RNA cleavages occur. These processes require many small
      nucleolar RNAs (snoRNAs) and proteins. Rbm19/Mrd1 is one such protein that is
      built from multiple RNA-binding domains (RBDs). We find that Rbm19/Mrd1 with five
      RBDs is present in all branches of the eukaryotic phylogenetic tree, except in
      animals and Choanoflagellates, that instead have a version with six RBDs and
      Microsporidia which have a minimal Rbm19/Mrd1 protein with four RBDs. Rbm19/Mrd1
      therefore evolved as a multi-RBD protein very early in eukaryotes. The linkers
      between the RBDs have conserved properties; they are disordered, except for
      linker 3, and position the RBDs at conserved relative distances from each other.
      All but one of the RBDs have conserved properties for RNA-binding and each RBD
      has a specific consensus sequence and a conserved position in the protein,
      suggesting a functionally important modular design. The patterns of evolutionary
      conservation provide information for experimental analyses of the function of
      Rbm19/Mrd1. In vivo mutational analysis confirmed that a highly conserved loop 5
      beta4-strand in RBD6 is essential for function.

PMID- 22984445
TI  - The crucial role of divalent metal ions in the DNA-acting efficacy and inhibition
      of the transcription of dimeric chromomycin A3.
AB  - Chromomycin A3 (Chro) is capable of forming a stable dimeric complex via
      chelation with Ni(II), Fe(II) and Co(II). According to the circular dichroism
      study, the dimer conformations are significantly different among the Fe(II)-,
      Co(II)-, and Ni(II)-containing dimeric Chro complexes; however, the dimer
      conformations were preserved at high temperatures. Furthermore, we conducted a
      systematic study to determine the effects of these divalent metal ions on the DNA
      acting efficacy of dimeric Chro, including its DNA-binding affinity, DNA
      stabilization capacity, DNA cleavage activity, and the inhibition of
      transcription both in vitro and within cells. Kinetic analyses using surface
      plasmon resonance (SPR) showed that Ni(II)(Chro)(2) exhibited the highest K(a)
      with a value of 1.26 * 10(7) M(-1), which is approximately 1.6- and 3.7-fold
      higher than the K(a) values obtained for Co(II)(Chro)(2) and Fe(II)(Chro)(2),
      respectively. The T(m) and DeltaG values for the DNA duplex increased after the
      addition of drug complexes in the following order:
      Ni(II)(Chro)(2)>Co(II)(Chro)(2)>Fe(II)(Chro)(2). In the DNA integrity assays, the
      DNA cleavage rate of Co(II)(Chro)(2) (1.2 * 10(-3) s(-1)) is higher than those of
      Fe(II)(Chro)(2) and Ni(II)(Chro)(2), which were calculated to be 1 * 10(-4) and
      3.1 * 10(-4) s(-1), respectively. Consistent with the SPR and UV melting results,
      Ni(II)(Chro)(2) possesses the highest inhibitory effect on in vitro transcription
      and c-myc transcription within cells compared to Co(II)(Chro)(2) and
      Fe(II)(Chro)(2). By comparing the cytotoxicity among Co(II)(Chro)(2),
      Fe(II)(Chro)(2), and Ni(II)(Chro)(2) to several cancer cell lines, our studies
      concluded that Ni(II)(Chro)(2) displayed more potential antitumor activities than
      Co(II)(Chro)(2) and Fe(II)(Chro)(2) did due to its higher DNA-acting efficacy.
      Changes to the divalent metal ions in the dimeric Chro complexes have been
      correlated with improved anticancer profiles. The availability of new metal
      derivatives of Chro may introduce new possibilities for exploiting the unique
      properties of this class of compounds for therapeutic applications.

PMID- 22984447
TI  - The consequences of high cigarette excise taxes for low-income smokers.
AB  - BACKGROUND: To illustrate the burden of high cigarette excise taxes on low-income
      smokers. METHODOLOGY/PRINCIPAL FINDINGS: Using data from the New York and
      national Adult Tobacco Surveys from 2010-2011, we estimated how smoking
      prevalence, daily cigarette consumption, and share of annual income spent on
      cigarettes vary by annual income (less than $30,000; $30,000-$59,999; and more
      than $60,000). The 2010-2011 sample includes 7,536 adults and 1,294 smokers from
      New York and 3,777 adults and 748 smokers nationally. Overall, smoking prevalence
      is lower in New York (16.1%) than nationally (22.2%) and is strongly associated
      with income in New York and nationally (P<.001). Smoking prevalence ranges from
      12.2% to 33.7% nationally and from 10.1% to 24.3% from the highest to lowest
      income group. In 2010-2011, the lowest income group spent 23.6% of annual
      household income on cigarettes in New York (up from 11.6% in 2003-2004) and 14.2%
      nationally. Daily cigarette consumption is not related to income.
      CONCLUSIONS/SIGNIFICANCE: Although high cigarette taxes are an effective method
      for reducing cigarette smoking, they can impose a significant financial burden on
      low-income smokers.

PMID- 22984446
TI  - Diversity of Xenorhabdus and Photorhabdus spp. and their symbiotic
      entomopathogenic nematodes from Thailand.
AB  - Xenorhabdus and Photorhabdus spp. are bacterial symbionts of entomopathogenic
      nematodes (EPNs). In this study, we isolated and characterized Xenorhabdus and
      Photorhabdus spp. from across Thailand together with their associated nematode
      symbionts, and characterized their phylogenetic diversity. EPNs were isolated
      from soil samples using a Galleria-baiting technique. Bacteria from EPNs were
      cultured and genotyped based on recA sequence. The nematodes were identified
      based on sequences of 28S rDNA and internal transcribed spacer regions. A total
      of 795 soil samples were collected from 159 sites in 13 provinces across
      Thailand. A total of 126 EPNs isolated from samples taken from 10 provinces were
      positive for Xenorhabdus (n = 69) or Photorhabdus spp. (n = 57). Phylogenetic
      analysis separated the 69 Xenorhabdus isolates into 4 groups. Groups 1, 2 and 3
      consisting of 52, 13 and 1 isolates related to X. stockiae, and group 4
      consisting of 3 isolates related to X. miraniensis. The EPN host for isolates
      related to X. stockiae was S. websteri, and for X. miraniensis was S. khoisanae.
      The Photorhabdus species were identified as P. luminescens (n = 56) and P.
      asymbiotica (n = 1). Phylogenenic analysis divided P. luminescens into five
      groups. Groups 1 and 2 consisted of 45 and 8 isolates defined as subspecies
      hainanensis and akhurstii, respectively. One isolate was related to hainanensis
      and akhurstii, two isolates were related to laumondii, and one isolate was the
      pathogenic species P. asymbiotica subsp. australis. H. indica was the major EPN
      host for Photorhabdus. This study reveals the genetic diversity of Xenorhabdus
      and Photorhabdus spp. and describes new associations between EPNs and their
      bacterial symbionts in Thailand.

PMID- 22984448
TI  - Using object oriented bayesian networks to model linkage, linkage disequilibrium
      and mutations between STR markers.
AB  - In a number of applications there is a need to determine the most likely pedigree
      for a group of persons based on genetic markers. Adequate models are needed to
      reach this goal. The markers used to perform the statistical calculations can be
      linked and there may also be linkage disequilibrium (LD) in the population. The
      purpose of this paper is to present a graphical Bayesian Network framework to
      deal with such data. Potential LD is normally ignored and it is important to
      verify that the resulting calculations are not biased. Even if linkage does not
      influence results for regular paternity cases, it may have substantial impact on
      likelihood ratios involving other, more extended pedigrees. Models for LD
      influence likelihoods for all pedigrees to some degree and an initial estimate of
      the impact of ignoring LD and/or linkage is desirable, going beyond mere rules of
      thumb based on marker distance. Furthermore, we show how one can readily include
      a mutation model in the Bayesian Network; extending other programs or formulas to
      include such models may require considerable amounts of work and will in many
      case not be practical. As an example, we consider the two STR markers vWa and
      D12S391. We estimate probabilities for population haplotypes to account for LD
      using a method based on data from trios, while an estimate for the degree of
      linkage is taken from the literature. The results show that accounting for
      haplotype frequencies is unnecessary in most cases for this specific pair of
      markers. When doing calculations on regular paternity cases, the markers can be
      considered statistically independent. In more complex cases of disputed
      relatedness, for instance cases involving siblings or so-called deficient cases,
      or when small differences in the LR matter, independence should not be assumed.
      (The networks are freely available at
      http://arken.umb.no/~dakl/BayesianNetworks.).

PMID- 22984449
TI  - High inorganic triphosphatase activities in bacteria and mammalian cells:
      identification of the enzymes involved.
AB  - BACKGROUND: We recently characterized a specific inorganic triphosphatase
      (PPPase) from Nitrosomonas europaea. This enzyme belongs to the CYTH superfamily
      of proteins. Many bacterial members of this family are annotated as predicted
      adenylate cyclases, because one of the founding members is CyaB adenylate cyclase
      from A. hydrophila. The aim of the present study is to determine whether other
      members of the CYTH protein family also have a PPPase activity, if there are
      PPPase activities in animal tissues and what enzymes are responsible for these
      activities. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant enzymes were expressed
      and purified as GST- or His-tagged fusion proteins and the enzyme activities were
      determined by measuring the release of inorganic phosphate. We show that the
      hitherto uncharacterized E. coli CYTH protein ygiF is a specific PPPase, but it
      contributes only marginally to the total PPPase activity in this organism, where
      the main enzyme responsible for hydrolysis of inorganic triphosphate (PPP(i)) is
      inorganic pyrophosphatase. We further show that CyaB hydrolyzes PPP(i) but this
      activity is low compared to its adenylate cyclase activity. Finally we
      demonstrate a high PPPase activity in mammalian and quail tissue, particularly in
      the brain. We show that this activity is mainly due to Prune, an
      exopolyphosphatase overexpressed in metastatic tumors where it promotes cell
      motility. CONCLUSIONS AND GENERAL SIGNIFICANCE: We show for the first time that
      PPPase activities are widespread in bacteria and animals. We identified the
      enzymes responsible for these activities but we were unable to detect significant
      amounts of PPP(i) in E. coli or brain extracts using ion chromatography and
      capillary electrophoresis. The role of these enzymes may be to hydrolyze PPP(i),
      which could be cytotoxic because of its high affinity for Ca(2+), thereby
      interfering with Ca(2+) signaling.

PMID- 22984450
TI  - Probiotic supplement use among young children in Taiwan: a prospective cohort
      study.
AB  - OBJECTIVES: The objective of this study is to provide details on probiotic
      supplement use among young children in Taiwan. PARTICIPANTS AND METHODS: This
      study is based on the Taiwan Birth Cohort Study database. We used questionnaires
      to collect information on probiotic supplement use among young children from
      birth to 18 months of age, while also considering their demographic
      characteristics and other covariates. Low-birth-weight infants, preterm infants,
      those with birth defects, and those with caregivers who returned incomplete
      questionnaires were excluded. The final valid sample comprised 16,991 cases.
      RESULTS: Approximately half the children received probiotic supplements before
      the age of 18 months. Only 6.3% of the children received probiotic supplements
      during the two periods of birth to 6 months and 7 to 18 months. Firstborn
      children, native mothers, mothers with higher educational levels, higher family
      income, and parents who lead healthy lifestyles were positively related to
      probiotic supplement use among children. Young children who were breastfed, with
      eczema, or with gastrointestinal tract problems were significantly positively
      associated with probiotic supplement use. CONCLUSION: The findings show that
      probiotic supplement usage among young children is associated with a more
      socially advantaged circumstance and certain child health factors, such as
      eczema, diarrhea, and constipation. Parents might use probiotic supplements for
      prevention or treatment of child diseases. The findings of this research could
      serve as a baseline for future studies, and provide insight into probiotic
      supplement use behavior for health professionals caring for infants and young
      children.

PMID- 22984451
TI  - Flavin mononucleotide-based fluorescent proteins function in mammalian cells
      without oxygen requirement.
AB  - Usage of the enhanced green fluorescent protein (eGFP) in living mammalian cells
      is limited to aerobic conditions due to requirement of oxygen during chromophore
      formation. Since many diseases or disease models are associated with acute or
      chronic hypoxia, eGFP-labeling of structures of interest in experimental studies
      might be unreliable leading to biased results. Thus, a chromophore yielding a
      stable fluorescence under hypoxic conditions is desirable. The fluorescence of
      flavin mononucleotide (FMN)-based fluorescent proteins (FbFPs) does not require
      molecular oxygen. Recently, the advantages of FbFPs for several bacterial strains
      and yeasts were described, specifically, their usage as a real time fluorescence
      marker in bacterial expression studies and their ability of chromophore formation
      under anaerobic conditions. Our objective was to verify if FbFPs also function in
      mammalian cells in order to potentially broaden the repertoire of chromophores
      with ones that can reliably be used in mammalian studies under hypoxic
      conditions. In the present study, we demonstrate for the first time, that FbFPs
      can be expressed in different mammalian cells, among them murine neural stem
      cells during proliferative and differentiated stages. Fluorescence intensities
      were comparable to eGFP. In contrast to eGFP, the FbFP fluorescence did not
      decrease when cells were exposed to defined hypoxic conditions neither in
      proliferating nor in differentiated cells. Thus, FbFPs can be regarded as an
      alternative to eGFP in studies that target cellular structures which are exposed
      to hypoxic conditions.

PMID- 22984452
TI  - Overexpression of SDF-1alpha enhanced migration and engraftment of cardiac stem
      cells and reduced infarcted size via CXCR4/PI3K pathway.
AB  - Cardiac stem cells (CSCs) can home to the infarcted area and regenerate
      myocardium. Stromal cell-derived factor-1alpha/C-X-C chemokine receptor type 4
      (SDF-1alpha/CXCR4) axis is pivotal in inducing CSCs migration. However, the
      mechanisms remain unclear. This study set out to detect if SDF-1alpha promotes
      migration and engraftment of CSCs through the CXCR4/PI3K (phosphatidylinositol 3
      kinase) pathway. In the in vitro experiment, c-kit+ cells were isolated from
      neonatal mouse heart fragment culture by magnetic cell sorting. Fluorescence
      activated cell sorting results demonstrated that a few c-kit+ cells expressed
      CD45 (4.54%) and Sca-1 (2.58%), the hematopoietic stem cell marker. Conditioned
      culture could induce c-kit+ cells multipotent differentiation, which was
      confirmed by cardiac troponin I (cTn-I), alpha-smooth muscle actin (alpha-SMA),
      and von Willebrand factor (vWF) staining. In vitro chemotaxis assays were
      performed using Transwell cell chambers to detect CSCs migration. The results
      showed that the cardiomyocytes infected with rAAV1-SDF-1alpha-eGFP significantly
      increased SDF-1alpha concentration, 5-fold more in supernatant than that in the
      control group, and subsequently attracted more CSCs migration. This effect was
      diminished by administration of AMD3100 (10 ug/ml, CXCR4 antagonist) or LY294002
      (20 umol/L, PI3K inhibitor). In myocardial infarction mice, overexpression of SDF
      1alpha in the infarcted area by rAAV1-SDF-1alpha-eGFP infection resulted in more
      CSCs retention to the infarcted myocardium, a higher percentage of proliferation,
      and reduced infarcted area which was attenuated by AMD3100 or ly294002
      pretreatment. These results indicated that overexpression of SDF-1alpha enhanced
      CSCs migration in vitro and engraftment of transplanted CSCs and reduced
      infarcted size via CXCR4/PI3K pathway.

PMID- 22984453
TI  - Variation in the maternal corticotrophin releasing hormone-binding protein (CRH
      BP) gene and birth weight in Blacks, Hispanics and Whites.
AB  - BACKGROUND: Given the unique role of the corticotrophin-releasing hormone (CRH)
      system in human fetal development, the aim of our study was to estimate the
      association of birth weight with DNA sequence variation in three maternal genes
      involved in regulating CRH production, bioavailability and action: CRH, CRH
      Binding Protein (CRH-BP), and CRH type 1 receptor (CRH-R1), respectively, in
      three racial groups (African-Americans, Hispanics, and non-Hispanic Whites).
      METHODS: Our study was carried out on a population-based sample of 575 mother
      child dyads. We resequenced the three genes in mouse-human hybrid somatic cell
      lines and selected SNPs for genotyping. RESULTS: A significant association was
      observed in each race between birth weight and maternal CRH-BP SNP genotypes.
      Estimates of linkage disequilibrium and haplotypes established three common
      haplotypes marked by the rs1053989 SNP in all three races. This SNP predicted
      significant birth weight variation after adjustment for gestational age, maternal
      BMI, parity, and smoking. African American and Hispanic mothers carrying the A
      allele had infants whose birth weight was on average 254 and 302 grams,
      respectively, less than infants having C/C mothers. Non-Hispanic White mothers
      homozygous for the A allele had infants who were on average 148 grams less than
      those infants having A/C and C/C mothers. CONCLUSIONS: The magnitudes of the
      estimates of the birth weight effects are comparable to the combined effects of
      multiple SNPs reported in a recent meta-analysis of 6 GWAS studies and is
      quantitatively larger than that associated with maternal cigarette smoking. This
      effect was persistent across subpopulations that vary with respect to ancestry
      and environment.

PMID- 22984454
TI  - Viscoelastic cell mechanics and actin remodelling are dependent on the rate of
      applied pressure.
AB  - BACKGROUND: Living cells are subjected to external and internal mechanical
      stresses. The effects of these stresses on the deformation and subsequent
      biological response of the cells remains unclear. This study tested the
      hypothesis that the rate at which pressure (or stress) is applied influence the
      viscoelastic properties of the cell associated with differences in the dynamics
      of the actin cytoskeleton. PRINCIPAL FINDING: Micropipette aspiration was used to
      determine the instantaneous and equilibrium moduli and the viscosity of isolated
      chondrocytes based on the standard linear solid (SLS) model and a variation of
      this incorporating Boltzmann superposition. Cells were visualised for 180 seconds
      following aspiration to 7 cmH(2)O at 0.35, 0.70 and 5.48 cmH(2)O/sec. Cell
      recovery was then examined for a further 180 seconds once the pressure had been
      removed. Reducing the rate of application of pressure reduced the levels of cell
      deformation and recovery associated with a significant increase in modulus and
      viscosity. Using GFP transfection and confocal microscopy, we show that
      chondrocyte deformation involves distortion, disassembly and subsequent
      reassembly of the cortical actin cytoskeleton. At faster pressure rates, cell
      deformation produced an increase in cell volume associated with membrane bleb
      formation. GFP-actin transfection inhibited the pressure rate dependent variation
      in cell mechanics indicating that this behaviour is regulated by GFP-sensitive
      actin dynamics. CONCLUSION: We suggest that slower rates of aspiration pressure
      enable greater levels of cortical actin distortion. This is partially inhibited
      by GFP or faster aspiration rates leading to membrane bleb formation and an
      increase in cell volume. Thus the rate of application of pressure regulates the
      viscoelastic mechanical properties of living cells through pressure rate
      sensitive differences in actin dynamics. Therefore cells appear softer when
      aspirated at a faster rate in contrast to what is expected of a normal
      viscoelastic material.

PMID- 22984455
TI  - Time-dependent statistical and correlation properties of neural signals during
      handwriting.
AB  - To elucidate the cortical control of handwriting, we examined time-dependent
      statistical and correlational properties of simultaneously recorded 64-channel
      electroencephalograms (EEGs) and electromyograms (EMGs) of intrinsic hand
      muscles. We introduced a statistical method, which offered advantages compared to
      conventional coherence methods. In contrast to coherence methods, which operate
      in the frequency domain, our method enabled us to study the functional
      association between different neural regions in the time domain. In our
      experiments, subjects performed about 400 stereotypical trials during which they
      wrote a single character. These trials provided time-dependent EMG and EEG data
      capturing different handwriting epochs. The set of trials was treated as a
      statistical ensemble, and time-dependent correlation functions between neural
      signals were computed by averaging over that ensemble. We found that trial-to
      trial variability of both the EMGs and EEGs was well described by a log-normal
      distribution with time-dependent parameters, which was clearly distinguished from
      the normal (Gaussian) distribution. We found strong and long-lasting EMG/EMG
      correlations, whereas EEG/EEG correlations, which were also quite strong, were
      short-lived with a characteristic correlation durations on the order of 100 ms or
      less. Our computations of correlation functions were restricted to the [Formula:
      see text] spectral range (13-30 Hz) of EEG signals where we found the strongest
      effects related to handwriting. Although, all subjects involved in our
      experiments were right-hand writers, we observed a clear symmetry between left
      and right motor areas: inter-channel correlations were strong if both channels
      were located over the left or right hemispheres, and 2-3 times weaker if the EEG
      channels were located over different hemispheres. Although we observed
      synchronized changes in the mean energies of EEG and EMG signals, we found that
      EEG/EMG correlations were much weaker than EEG/EEG and EMG/EMG correlations. The
      absence of strong correlations between EMG and EEG signals indicates that (i) a
      large fraction of the EEG signal includes electrical activity unrelated to low
      level motor variability; (ii) neural processing of cortically-derived signals by
      spinal circuitry may reduce the correlation between EEG and EMG signals.

PMID- 22984459
TI  - Interactions among vascular-tone modulators contribute to high altitude pulmonary
      edema and augmented vasoreactivity in highlanders.
AB  - BACKGROUND: The interactions among various biomarkers remained unexplored under
      the stressful environment of high-altitude. Present study evaluated interactions
      among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE)
      in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in
      comparison to HAPE-free sojourners (HAPE-f). METHODOLOGY/PRINCIPAL FINDINGS: All
      the subjects were recruited at 3500 m. We measured clinical parameters,
      biochemical levels in plasma and gene expression using RNA from blood; analyzed
      various correlations between and among the clinical parameters, especially
      arterial oxygen saturation (SaO(2)) and mean arterial pressure (MAP) and
      biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5
      HT), 8-iso-prostaglandin F2alpha (8-isoPGF2alpha), endothelin-1 (ET-1), plasma
      renin activity (PRA), plasma aldosterone concentration (PAC), superoxide
      dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8
      isoPGF2alpha, ET-1 levels, and PAC were significantly higher (p<0.0001, each),
      whereas SOD activity and NO level were significantly lower in HAPE-p than HAPE-f
      (p <= 0.001). Furthermore, ADMA, 5-HT, 8-isoPGF2alpha, NO levels and PAC were
      significantly higher (p<0.0001), whereas ET-1 level significantly (p<0.0001) and
      SOD activity non-significantly (p>0.05) lower in HLs than HAPE-f. The expression
      of respective genes differed in the three groups. In the correlations, SaO(2)
      inversely correlated with ADMA, 5-HT and 8-isoPGF2alpha and positively with SOD
      in HAPE-p (p<=0.009). MAP correlated positively with 5-HT and 8-isoPGF2alpha in
      HAPE-p and HLs (p <= 0.004). A strong positive correlation was observed between
      ADMA and 5-HT, 5-HT and 8-isoPGF2alpha (p<=0.001), whereas inverse correlation of
      SOD with ET-1 in HAPE-p and HLs (p <= 0.004), with 5-HT and 8-isoPGF2alpha in
      HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05). CONCLUSIONS/SIGNIFICANCE: The
      interactions among these markers confer enhanced vascular activity in HLs and
      HAPE in sojourners.

PMID- 22984461
TI  - Global coverage of cetacean line-transect surveys: status quo, data gaps and
      future challenges.
AB  - Knowledge of abundance, trends and distribution of cetacean populations is needed
      to inform marine conservation efforts, ecosystem models and spatial planning. We
      compiled a geo-spatial database of published data on cetacean abundance from
      dedicated visual line-transect surveys and encoded >1100 abundance estimates for
      47 species from 430 surveys conducted worldwide from 1975-2005. Our subsequent
      analyses revealed large spatial, temporal and taxonomic variability and gaps in
      survey coverage. With the exception of Antarctic waters, survey coverage was
      biased toward the northern hemisphere, especially US and northern European
      waters. Overall, <25% of the world's ocean surface was surveyed and only 6% had
      been covered frequently enough (>= 5 times) to allow trend estimation. Almost
      half the global survey effort, defined as total area (km(2)) covered by all
      survey study areas across time, was concentrated in the Eastern Tropical Pacific
      (ETP). Neither the number of surveys conducted nor the survey effort had
      increased in recent years. Across species, an average of 10% of a species'
      predicted range had been covered by at least one survey, but there was
      considerable variation among species. With the exception of three delphinid
      species, <1% of all species' ranges had been covered frequently enough for trend
      analysis. Sperm whales emerged from our analyses as a relatively data-rich
      species. This is a notoriously difficult species to survey visually, and we use
      this as an example to illustrate the challenges of using available data from line
      transect surveys for the detection of trends or for spatial planning. We propose
      field and analytical methods to fill in data gaps to improve cetacean
      conservation efforts.

PMID- 22984465
TI  - Feelings of disgust and disgust-induced avoidance weaken following induced sexual
      arousal in women.
AB  - BACKGROUND: Sex and disgust are basic, evolutionary relevant functions that are
      often construed as paradoxical. In general the stimuli involved in sexual
      encounters are, at least out of context strongly perceived to hold high disgust
      qualities. Saliva, sweat, semen and body odours are among the strongest disgust
      elicitors. This results in the intriguing question of how people succeed in
      having pleasurable sex at all. One possible explanation could be that sexual
      engagement temporarily reduces the disgust eliciting properties of particular
      stimuli or that sexual engagement might weaken the hesitation to actually
      approach these stimuli. METHODOLOGY: Participants were healthy women (n = 90)
      randomly allocated to one of three groups: the sexual arousal, the non-sexual
      positive arousal, or the neutral control group. Film clips were used to elicit
      the relevant mood state. Participants engaged in 16 behavioural tasks, involving
      sex related (e.g., lubricate the vibrator) and non-sex related (e.g., take a sip
      of juice with a large insect in the cup) stimuli, to measure the impact of sexual
      arousal on feelings of disgust and actual avoidance behaviour. PRINCIPAL
      FINDINGS: The sexual arousal group rated the sex related stimuli as less
      disgusting compared to the other groups. A similar tendency was evident for the
      non-sex disgusting stimuli. For both the sex and non-sex related behavioural
      tasks the sexual arousal group showed less avoidance behaviour (i.e., they
      conducted the highest percentage of tasks compared to the other groups).
      SIGNIFICANCE: This study has investigated how sexual arousal interplays with
      disgust and disgust eliciting properties in women, and has demonstrated that this
      relationship goes beyond subjective report by affecting the actual approach to
      disgusting stimuli. Hence, this could explain how we still manage to engage in
      pleasurable sexual activity. Moreover, these findings suggest that low sexual
      arousal might be a key feature in the maintenance of particular sexual
      dysfunctions.

PMID- 22984458
TI  - Temporal properties of liquid crystal displays: implications for vision science
      experiments.
AB  - Liquid crystal displays (LCD) are currently replacing the previously dominant
      cathode ray tubes (CRT) in most vision science applications. While the properties
      of the CRT technology are widely known among vision scientists, the photometric
      and temporal properties of LCDs are unfamiliar to many practitioners. We provide
      the essential theory, present measurements to assess the temporal properties of
      different LCD panel types, and identify the main determinants of the photometric
      output. Our measurements demonstrate that the specifications of the manufacturers
      are insufficient for proper display selection and control for most purposes.
      Furthermore, we show how several novel display technologies developed to improve
      fast transitions or the appearance of moving objects may be accompanied by side
      effects in some areas of vision research. Finally, we unveil a number of
      surprising technical deficiencies. The use of LCDs may cause problems in several
      areas in vision science. Aside from the well-known issue of motion blur, the main
      problems are the lack of reliable and precise onsets and offsets of displayed
      stimuli, several undesirable and uncontrolled components of the photometric
      output, and input lags which make LCDs problematic for real-time applications. As
      a result, LCDs require extensive individual measurements prior to applications in
      vision science.

PMID- 22984457
TI  - Ablation of dihydroceramide desaturase confers resistance to etoposide-induced
      apoptosis in vitro.
AB  - Sphingolipid biosynthesis is potently upregulated by factors associated with
      cellular stress, including numerous chemotherapeutics, inflammatory cytokines,
      and glucocorticoids. Dihydroceramide desaturase 1 (Des1), the third enzyme in the
      highly conserved pathway driving sphingolipid biosynthesis, introduces the 4,5
      trans-double bond that typifies most higher-order sphingolipids. Surprisingly,
      recent studies have shown that certain chemotherapeutics and other drugs inhibit
      Des1, giving rise to a number of sphingolipids that lack the characteristic
      double bond. In order to assess the effect of an altered sphingolipid profile
      (via Des1 inhibition) on cell function, we generated isogenic mouse embryonic
      fibroblasts lacking both Des1 alleles. Lipidomic profiling revealed that these
      cells contained higher levels of dihydroceramide than wild-type fibroblasts and
      that complex sphingolipids were comprised predominantly of the saturated backbone
      (e.g. sphinganine vs. sphingosine, dihydrosphingomyelin vs. sphingomyelin, etc.).
      Des1 ablation activated pro-survival and anabolic signaling intermediates (e.g.
      Akt/PKB, mTOR, MAPK, etc.) and provided protection from apoptosis caused by
      etoposide, a chemotherapeutic that induces sphingolipid synthesis by upregulating
      several sphingolipid biosynthesizing enzymes. These data reveal that the double
      bond present in most sphingolipids has a profound impact on cell survival
      pathways, and that the manipulation of Des1 could have important effects on
      apoptosis.

PMID- 22984456
TI  - A Bmp reporter with ultrasensitive characteristics reveals that high Bmp
      signaling is not required for cortical hem fate.
AB  - Insights into Bone morphogenetic protein (Bmp) functions during forebrain
      development have been limited by a lack of Bmp signaling readouts. Here we used a
      novel Bmp signaling reporter ("BRE-gal" mice) to study Bmp signaling in the
      dorsal telencephalon. At early stages, BRE-gal expression was restricted to the
      dorsal telencephalic midline. At later stages, strong BRE-gal expression occurred
      in neurons of the marginal zone and dentate gyrus. Comparisons to nuclear phospho
      Smad1/5/8 (pSmad) and Msx1 indicated that BRE-gal expression occurred exclusively
      in neural cells with high-level Bmp signaling. BRE-gal responsiveness to Bmps was
      confirmed in reporter-negative cortical cells cultured with Bmp4, and both in
      vivo and in vitro, BRE-gal expression was switch-like, or ultrasensitive. In the
      early dorsal telencephalon, BRE-gal expression negatively correlated with the
      cortical selector gene Lhx2, indicating a BRE-gal expression border that
      coincides with the cortex-hem boundary. However, in Lhx2 null chimeras, neither
      BRE-gal nor nuclear pSmad increases were observed in ectopic hem cells. These
      findings establish BRE-gal as an ultrasensitive reporter of Bmp signaling in the
      dorsal telencephalon, imply that hem fate can be specified at different Bmp
      signaling intensities, and suggest that Lhx2 primarily regulates the responses to
      -rather than the intensity of--Bmp signaling in dorsal telencephalic cells.

PMID- 22984460
TI  - Intrinsic brain connectivity related to age in young and middle aged adults.
AB  - Age-related variations in resting state connectivity of the human brain were
      examined from young adulthood through middle age. A voxel-based network measure,
      degree, was used to assess age-related differences in tissue connectivity
      throughout the brain. Increases in connectivity with age were found in paralimbic
      cortical and subcortical regions. Decreases in connectivity were found in
      cortical regions, including visual areas and the default mode network. These
      findings differ from those of recent developmental studies examining earlier
      growth trajectories, and are consistent with known changes in cognitive function
      and emotional processing during mature aging. The results support and extend
      previous findings that relied on a priori definitions of regions of interest for
      their analyses. This approach of applying a voxel-based measure to examine the
      functional connectivity of individual tissue elements over time, without the need
      for a priori region of interest definitions, provides an important new tool in
      brain science.

PMID- 22984463
TI  - A three-dimensional stereotaxic MRI brain atlas of the cichlid fish Oreochromis
      mossambicus.
AB  - The African cichlid Oreochromis mossambicus (Mozambique tilapia) has been used as
      a model system in a wide range of behavioural and neurobiological studies. The
      increasing number of genetic tools available for this species, together with the
      emerging interest in its use for neurobiological studies, increased the need for
      an accurate hodological mapping of the tilapia brain to supplement the available
      histological data. The goal of our study was to elaborate a three-dimensional,
      high-resolution digital atlas using magnetic resonance imaging, supported by
      Nissl staining. Resulting images were viewed and analysed in all orientations
      (transverse, sagittal, and horizontal) and manually labelled to reveal structures
      in the olfactory bulb, telencephalon, diencephalon, optic tectum, and cerebellum.
      This high resolution tilapia brain atlas is expected to become a very useful tool
      for neuroscientists using this fish model and will certainly expand their use in
      future studies regarding the central nervous system.

PMID- 22984466
TI  - Personalised normative feedback for preventing alcohol misuse in university
      students: Solomon three-group randomised controlled trial.
AB  - BACKGROUND: Young people tend to over-estimate peer group drinking levels.
      Personalised normative feedback (PNF) aims to correct this misperception by
      providing information about personal drinking levels and patterns compared with
      norms in similar aged peer groups. PNF is intended to raise motivation for
      behaviour change and has been highlighted for alcohol misuse prevention by the
      British Government Behavioural Insight Team. The objective of the trial was to
      assess the effectiveness of PNF with college students for the prevention of
      alcohol misuse. METHODOLOGY: Solomon three-group randomised controlled trial.
      1751 students, from 22 British Universities, allocated to a PNF group, a normal
      control group, or a delayed measurement control group to allow assessment of any
      measurement effects. PNF was provided by email. Participants completed online
      questionnaires at baseline, 6- and 12-months (only 12-months for the delayed
      measurement controls). Drinking behaviour measures were (i) alcohol disorders;
      (ii) frequency; (iii) typical quantity, (iv) weekly consumption; (v) alcohol
      related problems; (vi) perceived drinking norms; and (vii) positive alcohol
      expectancies. Analyses focused on high-risk drinkers, as well as all students,
      because of research evidence for the prevention paradox in student drinkers.
      PRINCIPAL FINDINGS: Follow-up rates were low, with only 50% and 40% responding at
      6- and 12-months, respectively, though comparable to similar European studies. We
      found no evidence for any systematic attrition bias. Overall, statistical
      analyses with the high risk sub-sample, and for all students, showed no
      significant effects of the intervention, at either time-point, in a completed
      case analysis and a multiple imputation analysis. CONCLUSIONS: We found no
      evidence for the effectiveness of PNF for the prevention of alcohol misuse and
      alcohol-related problems in a UK student population. REGISTRATION: Controlled
      Trials.com ISRCTN30784467.

PMID- 22984462
TI  - Auditory processing in high-functioning adolescents with Autism Spectrum
      Disorder.
AB  - Autism Spectrum Disorder (ASD) is a pervasive developmental disorder including
      abnormalities in perceptual processing. We measure perception in a battery of
      tests across speech (filtering, phoneme categorization, multisensory integration)
      and music (pitch memory, meter categorization, harmonic priming). We found that
      compared to controls, the ASD group showed poorer filtering, less audio-visual
      integration, less specialization for native phonemic and metrical categories, and
      a higher instance of absolute pitch. No group differences were found in harmonic
      priming. Our results are discussed in a developmental framework where culture
      specific knowledge acquired early compared to late in development is most
      impaired, perhaps because of early-accelerated brain growth in ASD. These results
      suggest that early auditory remediation is needed for good communication and
      social functioning.

PMID- 22984464
TI  - Highly pathogenic avian influenza virus among wild birds in Mongolia.
AB  - Mongolia combines a near absence of domestic poultry, with an abundance of
      migratory waterbirds, to create an ideal location to study the epidemiology of
      highly pathogenic avian influenza virus (HPAIV) in a purely wild bird system.
      Here we present the findings of active and passive surveillance for HPAIV subtype
      H5N1 in Mongolia from 2005-2011, together with the results of five outbreak
      investigations. In total eight HPAIV outbreaks were confirmed in Mongolia during
      this period. Of these, one was detected during active surveillance employed by
      this project, three by active surveillance performed by Mongolian government
      agencies, and four through passive surveillance. A further three outbreaks were
      recorded in the neighbouring Tyva Republic of Russia on a lake that bisects the
      international border. No HPAIV was isolated (cultured) from 7,855 environmental
      fecal samples (primarily from ducks), or from 2,765 live, clinically healthy
      birds captured during active surveillance (primarily shelducks, geese and swans),
      while four HPAIVs were isolated from 141 clinically ill or dead birds located
      through active surveillance. Two low pathogenic avian influenza viruses (LPAIV)
      were cultured from ill or dead birds during active surveillance, while
      environmental feces and live healthy birds yielded 56 and 1 LPAIV respectively.
      All Mongolian outbreaks occurred in 2005 and 2006 (clade 2.2), or 2009 and 2010
      (clade 2.3.2.1); all years in which spring HPAIV outbreaks were reported in Tibet
      and/or Qinghai provinces in China. The occurrence of outbreaks in areas deficient
      in domestic poultry is strong evidence that wild birds can carry HPAIV over at
      least moderate distances. However, failure to detect further outbreaks of clade
      2.2 after June 2006, and clade 2.3.2.1 after June 2010 suggests that wild birds
      migrating to and from Mongolia may not be competent as indefinite reservoirs of
      HPAIV, or that HPAIV did not reach susceptible populations during our study.

PMID- 22984467
TI  - A population accounting approach to assess tourism contributions to conservation
      of IUCN-redlisted mammal species.
AB  - Over 1,000 mammal species are red-listed by IUCN, as Critically Endangered,
      Endangered or Vulnerable. Conservation of many threatened mammal species, even
      inside protected areas, depends on costly active day-to-day defence against
      poaching, bushmeat hunting, invasive species and habitat encroachment. Many parks
      agencies worldwide now rely heavily on tourism for routine operational funding:
      >50% in some cases. This puts rare mammals at a new risk, from downturns in
      tourism driven by external socioeconomic factors. Using the survival of
      individual animals as a metric or currency of successful conservation, we
      calculate here what proportions of remaining populations of IUCN-redlisted mammal
      species are currently supported by funds from tourism. This proportion is >= 5%
      for over half of the species where relevant data exist, >= 15% for one fifth, and
      up to 66% in a few cases. Many of these species, especially the most endangered,
      survive only in one single remaining subpopulation. These proportions are not
      correlated either with global population sizes or recognition as wildlife tourism
      icons. Most of the more heavily tourism-dependent species, however, are medium
      sized (>7.5 kg) or larger. Historically, biological concern over the growth of
      tourism in protected areas has centered on direct disturbance to wildlife. These
      results show that conservation of threatened mammal species has become reliant on
      revenue from tourism to a previously unsuspected degree. On the one hand, this
      provides new opportunities for conservation funding; but on the other, dependence
      on such an uncertain source of funding is a new, large and growing threat to red
      listed species.

PMID- 22984468
TI  - Micromechanics of Sea Urchin spines.
AB  - The endoskeletal structure of the Sea Urchin, Centrostephanus rodgersii, has
      numerous long spines whose known functions include locomotion, sensing, and
      protection against predators. These spines have a remarkable internal
      microstructure and are made of single-crystal calcite. A finite-element model of
      the spine's unique porous structure, based on micro-computed tomography (microCT)
      and incorporating anisotropic material properties, was developed to study its
      response to mechanical loading. Simulations show that high stress concentrations
      occur at certain points in the spine's architecture; brittle cracking would
      likely initiate in these regions. These analyses demonstrate that the
      organization of single-crystal calcite in the unique, intricate morphology of the
      sea urchin spine results in a strong, stiff and lightweight structure that
      enhances its strength despite the brittleness of its constituent material.

PMID- 22984469
TI  - A large insertion in bHLH transcription factor BrTT8 resulting in yellow seed
      coat in Brassica rapa.
AB  - Yellow seed is a desirable quality trait of the Brassica oilseed species.
      Previously, several seed coat color genes have been mapped in the Brassica
      species, but the molecular mechanism is still unknown. In the present
      investigation, map-based cloning method was used to identify a seed coat color
      gene, located on A9 in B. rapa. Blast analysis with the Arabidopsis genome showed
      that there were 22 Arabidopsis genes in this region including at4g09820 to
      at4g10620. Functional complementation test exhibited a phenotype reversion in the
      Arabidopsis thaliana tt8-1 mutant and yellow-seeded plant. These results
      suggested that the candidate gene was a homolog of TRANSPARENT TESTA8 (TT8)
      locus. BrTT8 regulated the accumulation of proanthocyanidins (PAs) in the seed
      coat. Sequence analysis of two alleles revealed a large insertion of a new class
      of transposable elements, Helitron in yellow sarson. In addition, no mRNA
      expression of BrTT8 was detected in the yellow-seeded line. It indicated that the
      natural transposon might have caused the loss in function of BrTT8. BrTT8 encodes
      a basic/helix-loop-helix (bHLH) protein that shares a high degree of similarity
      with other bHLH proteins in the Brassica. Further expression analysis also
      revealed that BrTT8 was involved in controlling the late biosynthetic genes
      (LBGs) of the flavonoid pathway. Our present findings provided with further
      studies could assist in understanding the molecular mechanism involved in seed
      coat color formation in Brassica species, which is an important oil yielding
      quality trait.

PMID- 22984470
TI  - Complementarity of end regions increases the lifetime of small RNAs in mammalian
      cells.
AB  - Two RNAs (4.5SH and 4.5SI) with unknown functions share a number of features:
      short length (about 100 nt), transcription by RNA polymerase III, predominately
      nuclear localization, the presence in various tissues, and relatively narrow
      taxonomic distribution (4 and 3 rodent families, respectively). It was reported
      that 4.5SH RNA turns over rapidly, whereas 4.5SI RNA is stable in the cell, but
      their lifetimes remained unknown. We showed that 4.5SH is indeed short-lived
      (t(1/2)~18 min) and 4.5SI is long-lived (t(1/2)~22 h) in Krebs ascites carcinoma
      cells. The RNA structures specifying rapid or slow decay of different small
      cellular RNAs remain unstudied. We searched for RNA structural features that
      determine the short lifetime of 4.5SH in comparison with the long lifetime of
      4.5SI RNA. The sequences of genes of 4.5SH and 4.5SI RNAs were altered and human
      cells (HeLa) were transfected with these genes. The decay rate of the original
      and altered RNAs was measured. The complementarity of 16-nt end regions of 4.5SI
      RNA proved to contribute to its stability in cells, whereas the lack of such
      complementarity in 4.5SH RNA caused its rapid decay. Possible mechanisms of the
      phenomenon are discussed.

PMID- 22984471
TI  - The association of cysteine with obesity, inflammatory cytokines and insulin
      resistance in Hispanic children and adolescents.
AB  - CONTEXT: Plasma total cysteine (tCys) independently relates to fat mass in
      adults. Dietary cyst(e)ine promotes adiposity and decreases glucose tolerance in
      some rodent models, but alleviates insulin resistance in others. OBJECTIVE: To
      investigate whether the association of tCys with body fat extends to children at
      particular risk of obesity, and whether tCys is associated with insulin
      resistance and obesity-associated inflammation. METHODS: We explored the cross
      sectional relations of fasting plasma tCys and related metabolites with body
      composition measured by dual-energy X-ray absorptiometry in 984 Hispanic children
      and adolescents aged 4-19 years from the Viva La Familia Study. Linear and
      logistic regression and dose-response curves were used to evaluate relations of
      tCys with obesity, insulin resistance and inflammatory markers including
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte
      chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP). RESULTS: tCys,
      methionine and total homocysteine (tHcy) increased with age. Upper tCys quartile
      was independently associated with a 5-fold increased risk of obesity (95% CI 3.5
      8.0, P<0.001), and 2-fold risk of insulin resistance (95% CI: 1.6-5.0, P<0.001;
      adjusted for body fat%). Within the overweight/obese subgroup, but not in normal
      weight children, tCys accounted for 9% of the variability in body fat% (partial r
      = 0.30, P<0.001; adjusted for age and gender). tCys correlated positively with
      serum non-esterified fatty acids and leptin, partly independent of body fat, but
      was not associated with serum IL-6, TNF-alpha or MCP-1. A positive correlation
      with CRP disappeared after adjustment for BMI. CONCLUSION: tCys is independently
      associated with obesity and insulin resistance in Hispanic children and
      adolescents, highlighting a previously underappreciated link between the sulfur
      amino acid metabolic pathway and obesity and cardiometabolic risk.

PMID- 22984472
TI  - Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to
      oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo.
AB  - Oxalate is a metabolic end product excreted by the kidney. Mild increases in
      urinary oxalate are most commonly associated with Nephrolithiasis. Chronically
      high levels of urinary oxalate, as seen in patients with primary hyperoxaluria,
      are driving factor for recurrent renal stones, and ultimately lead to renal
      failure, calcification of soft tissue and premature death. In previous studies
      others and we have demonstrated that high levels of oxalate promote injury of
      renal epithelial cells. However, methods to monitor oxalate induced renal injury
      are limited. In the present study we evaluated changes in expression of Kidney
      Injury Molecule-1 (KIM-1) in response to oxalate in human renal cells (HK2 cells)
      in culture and in renal tissue and urine samples in hyperoxaluric animals which
      mimic in vitro and in vivo models of hyper-oxaluria. Results presented, herein
      demonstrate that oxalate exposure resulted in increased expression of KIM-1 m RNA
      as well as protein in HK2 cells. These effects were rapid and concentration
      dependent. Using in vivo models of hyperoxaluria we observed elevated expression
      of KIM-1 in renal tissues of hyperoxaluric rats as compared to normal controls.
      The increase in KIM-1 was both at protein and mRNA level, suggesting
      transcriptional activation of KIM-1 in response to oxalate exposure.
      Interestingly, in addition to increased KIM-1 expression, we observed increased
      levels of the ectodomain of KIM-1 in urine collected from hyperoxaluric rats. To
      the best of our knowledge our studies are the first direct demonstration of
      regulation of KIM-1 in response to oxalate exposure in renal epithelial cells in
      vitro and in vivo. Our results suggest that detection of KIM-1 over-expression
      and measurement of the ectodomain of KIM-1 in urine may hold promise as a marker
      to monitor oxalate nephrotoxicity in hyperoxaluria.

PMID- 22984473
TI  - The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer
      irradiation.
AB  - Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000
      new cases reported annually in the United States. Due to early detection and
      advances in therapies, more than 90% of patients will survive 10 years post
      diagnosis and treatment. Radiation is a treatment option often used to treat
      localized disease; however, while radiation is very effective at killing tumor
      cells, normal tissues are damaged as well. Potential side-effects due to prostate
      cancer-related radiation therapy include bowel inflammation, erectile
      dysfunction, urethral stricture, rectal bleeding and incontinence. Currently,
      radiation therapy for prostate cancer does not include the administration of
      therapeutic agents to reduce these side effects and protect normal tissues from
      radiation-induced damage. In the current study, we show that the small molecular
      weight antioxidant, MnTE-2-PyP, protects normal tissues from radiation-induced
      damage in the lower abdomen in rats. Specifically, MnTE-2-PyP protected skin,
      prostate, and testes from radiation-induced damage. MnTE-2-PyP also protected
      from erectile dysfunction, a persistent problem regardless of the type of
      radiation techniques used because the penile neurovascular bundles lay in the
      peripheral zones of the prostate, where most prostate cancers reside. Based on
      previous studies showing that MnTE-2-PyP, in combination with radiation, further
      reduces subcutaneous tumor growth, we believe that MnTE-2-PyP represents an
      excellent radioprotectant in combination radiotherapy for cancer in general and
      specifically for prostate cancer.

PMID- 22984474
TI  - Can we depend on investigators to identify and register randomized controlled
      trials?
AB  - PURPOSE: To reduce publication bias, systematic reviewers are advised to search
      conference abstracts to identify randomized controlled trials (RCTs) conducted in
      humans and not published in full. We assessed the information provided by authors
      to aid identification of RCTs for reviews. METHODS: We handsearched the
      Association for Research in Vision and Ophthalmology (ARVO) meeting abstracts for
      2004 to 2009 to identify reports of RCTs. We compared our classification with
      that of authors (requested by ARVO 2004-2006), and authors' report of trial
      registration (required by ARVO 2007-2009). RESULTS: Authors identified their
      study as a clinical trial for 169/191 (88%; 95% CI, 84-93) RCTs we identified for
      2004, 174/212 (82%; 95% CI, 77-87) for 2005 and 162/215 (75%; 95% CI, 70-81) for
      2006. Authors provided registration information for 107/172 (62%; 95% CI, 55-69)
      RCTs for 2007, 103/153 (67%; 95% CI, 60-75) for 2008, and 126/171 (74%; 95% CI,
      67-80) for 2009. Most RCT authors providing a trial register name specified
      ClinicalTrials.gov (276/312; 88%; 95% CI, 85-92) and provided a valid
      ClinicalTrials.gov registration number (261/276; 95%; 95% CI, 92-97). Based on
      information provided by authors, trial registration information would be
      accessible for 48% (83/172) (95% CI, 41-56) of all ARVO abstracts describing RCTs
      in 2007, 63% (96/153) (95% CI, 55-70) in 2008, and 70% in 2009 (118/171) (95% CI,
      62-76). CONCLUSIONS: Authors of abstracts describing RCTs frequently did not
      classify them as clinical trials nor comply with reporting trial registration
      information, as required by the conference organizers. Systematic reviewers
      cannot rely on authors to identify relevant unpublished trials or report trial
      registration, if present.

PMID- 22984475
TI  - Absorption of radionuclides from the Fukushima nuclear accident by a novel algal
      strain.
AB  - Large quantities of radionuclides have leaked from the Fukushima Daiichi Nuclear
      Power Plant into the surrounding environment. Effective prevention of health
      hazards resulting from radiation exposure will require the development of
      efficient and economical methods for decontaminating radioactive wastewater and
      aquatic ecosystems. Here we describe the accumulation of water-soluble
      radionuclides released by nuclear reactors by a novel strain of alga. The newly
      discovered green microalgae, Parachlorella sp. binos (Binos) has a thick alginate
      containing extracellular matrix and abundant chloroplasts. When this strain was
      cultured with radioiodine, a light-dependent uptake of radioiodine was observed.
      In dark conditions, radioiodine uptake was induced by addition of hydrogen
      superoxide. High-resolution secondary ion mass spectrometry (SIMS) showed a
      localization of accumulated iodine in the cytosol. This alga also exhibited
      highly efficient incorporation of the radioactive isotopes strontium and cesium
      in a light-independent manner. SIMS analysis showed that strontium was
      distributed in the extracellular matrix of Binos. Finally we also showed the
      ability of this strain to accumulate radioactive nuclides from water and soil
      samples collected from a heavily contaminated area in Fukushima. Our results
      demonstrate that Binos could be applied to the decontamination of iodine,
      strontium and cesium radioisotopes, which are most commonly encountered after
      nuclear reactor accidents.

PMID- 22984476
TI  - Molecular characterization of direct target genes and cis-acting consensus
      recognized by quorum-sensing regulator AphA in Vibrio parahaemolyticus.
AB  - BACKGROUND: AphA is the master quorum-sensing (QS) regulator operating at low
      cell density in vibrios. Molecular regulation of target genes by AphA has been
      characterized in Vibrio harveyi and V. cholerae, but it is still poorly
      understood in V. parahaemolyticus. METHODOLOGY/PRINCIPAL FINDINGS: The AphA
      proteins are extremely conserved in V. parahaemolyticus, Vibrio sp. Ex25, Vibrio
      sp. EJY3, V. harveyi, V. vulnificus, V. splendidus, V. anguillarum, V. cholerae,
      and V. furnissii. The above nine AphA orthologs appear to recognize conserved cis
      acting DNA signals which can be represented by two consensus constructs, a 20 bp
      box sequence and a position frequency matrix. V. parahaemolyticus AphA represses
      the transcription of ahpA, qrr4, and opaR through direct AphA-target promoter DNA
      association, while it inhibits the qrr2-3 transcription in an indirect manner.
      Translation and transcription starts, core promoter elements for sigma factor
      recognition, Shine-Dalgarno sequences for ribosome recognition, and AphA-binding
      sites (containing corresponding AphA box-like sequences) were determined for the
      three direct AphA targets ahpA, qrr4, and opaR in V. parahaemolyticus.
      CONCLUSIONS/SIGNIFICANCE: AphA-mediated repression of ahpA, qrr2-4, and opaR was
      characterized in V. parahaemolyticus by using multiple biochemical and molecular
      experiments. The computational promoter analysis indicated the conserved
      mechanism of transcriptional regulation of QS regulator-encoding genes ahpA,
      qrr4, and opaR in vibrios.

PMID- 22984477
TI  - Binary DNA nanostructures for data encryption.
AB  - We present a simple and secure system for encrypting and decrypting information
      using DNA self-assembly. Binary data is encoded in the geometry of DNA
      nanostructures with two distinct conformations. Removing or leaving out a single
      component reduces these structures to an encrypted solution of ssDNA, whereas
      adding back this missing "decryption key" causes the spontaneous formation of the
      message through self-assembly, enabling rapid read out via gel electrophoresis.
      Applications include authentication, secure messaging, and barcoding.

PMID- 22984478
TI  - Proteomic response to acupuncture treatment in spontaneously hypertensive rats.
AB  - Previous animal and clinical studies have shown that acupuncture is an effective
      alternative treatment in the management of hypertension, but the mechanism is
      unclear. This study investigated the proteomic response in the nervous system to
      treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats
      (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for
      7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7(th)
      day, rat medullas were dissected, homogenized, and subject to 2D gel
      electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure
      stabilized after the 5th day of acupuncture, and compared with non-acupoint
      treatment, Taichong-acupunctured rat's systolic pressure was reduced
      significantly (P<0.01), though not enough to bring blood pressure down to normal
      levels. The different treatment groups also showed differential protein
      expression: the 2D images revealed 571 +/- 15 proteins in normal SD rats'
      medulla, 576 +/- 31 proteins in SHR's medulla, 597 +/- 44 proteins in medulla of
      SHR after acupuncturing Taichong, and 616 +/- 18 proteins in medulla of SHR after
      acupuncturing non-acupoint. In the medulla of Taichong group, compared with non
      acupoint group, seven proteins were down-regulated: heat shock protein-90,
      synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein
      kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic
      protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde
      dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1,
      DJ-1 protein and superoxide dismutase. The altered expression of several proteins
      by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The
      results indicate an increase in antioxidant enzymes in the medulla of the SHRs
      subject to acupuncture, which may provide partial explanation for the
      antihypertensive effect of acupuncture. Further studies are warranted to
      investigate the role of oxidative stress modulation by acupuncture in the
      treatment of hypertension.

PMID- 22984479
TI  - Embryonic demise caused by targeted disruption of a cysteine protease Dub-2.
AB  - BACKGROUND: A plethora of biological metabolisms are regulated by the mechanisms
      of ubiquitination, wherein this process is balanced with the action of
      deubiquitination system. Dub-2 is an IL-2-inducible, immediate-early gene that
      encodes a deubiquitinating enzyme with growth regulatory activity. DUB-2
      presumably removes ubiquitin from ubiquitin-conjugated target proteins regulating
      ubiquitin-mediated proteolysis, but its specific target proteins are unknown yet.
      METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the functional role of Dub-2, we
      generated genetically modified mice by introducing neo cassette into the second
      exon of Dub-2 and then homologous recombination was done to completely abrogate
      the activity of DUB-2 proteins. We generated Dub-2+/- heterozygous mice showing a
      normal phenotype and are fertile, whereas new born mouse of Dub-2-/- homozygous
      alleles could not survive. In addition, Dub-2-/- embryo could not be seen between
      E6.5 and E12.5 stages. Furthermore, the number of embryos showing normal
      embryonic development for further stages is decreased in heterozygotes. Even
      embryonic stem cells from inner cell mass of Dub-2-/- embryos could not be
      established. CONCLUSIONS: Our study suggests that the targeted disruption of Dub
      2 may cause embryonic lethality during early gestation, possibly due to the
      failure of cell proliferation during hatching process.

PMID- 22984480
TI  - Identifying the evolutionary building blocks of the cardiac conduction system.
AB  - The endothermic state of mammals and birds requires high heart rates to
      accommodate the high rates of oxygen consumption. These high heart rates are
      driven by very similar conduction systems consisting of an atrioventricular node
      that slows the electrical impulse and a His-Purkinje system that efficiently
      activates the ventricular chambers. While ectothermic vertebrates have similar
      contraction patterns, they do not possess anatomical evidence for a conduction
      system. This lack amongst extant ectotherms is surprising because mammals and
      birds evolved independently from reptile-like ancestors. Using conserved genetic
      markers, we found that the conduction system design of lizard (Anolis
      carolinensis and A. sagrei), frog (Xenopus laevis) and zebrafish (Danio rerio)
      adults is strikingly similar to that of embryos of mammals (mouse Mus musculus,
      and man) and chicken (Gallus gallus). Thus, in ectothermic adults, the slow
      conducting atrioventricular canal muscle is present, no fibrous insulating plane
      is formed, and the spongy ventricle serves the dual purpose of conduction and
      contraction. Optical mapping showed base-to-apex activation of the ventricles of
      the ectothermic animals, similar to the activation pattern of mammalian and avian
      embryonic ventricles and to the His-Purkinje systems of the formed hearts.
      Mammalian and avian ventricles uniquely develop thick compact walls and septum
      and, hence, form a discrete ventricular conduction system from the embryonic
      spongy ventricle. Our study uncovers the evolutionary building plan of heart and
      indicates that the building blocks of the conduction system of adult ectothermic
      vertebrates and embryos of endotherms are similar.

PMID- 22984481
TI  - Polar/Ionizable residues in transmembrane segments: effects on helix-helix
      packing.
AB  - The vast majority of membrane proteins are anchored to biological membranes
      through hydrophobic alpha-helices. Sequence analysis of high-resolution membrane
      protein structures show that ionizable amino acid residues are present in
      transmembrane (TM) helices, often with a functional and/or structural role. Here,
      using as scaffold the hydrophobic TM domain of the model membrane protein
      glycophorin A (GpA), we address the consequences of replacing specific residues
      by ionizable amino acids on TM helix insertion and packing, both in detergent
      micelles and in biological membranes. Our findings demonstrate that ionizable
      residues are stably inserted in hydrophobic environments, and tolerated in the
      dimerization process when oriented toward the lipid face, emphasizing the
      complexity of protein-lipid interactions in biological membranes.

PMID- 22984482
TI  - Lesula: a new species of Cercopithecus monkey endemic to the Democratic Republic
      of Congo and implications for conservation of Congo's central basin.
AB  - In June 2007, a previously undescribed monkey known locally as "lesula" was found
      in the forests of the middle Lomami Basin in central Democratic Republic of Congo
      (DRC). We describe this new species as Cercopithecus lomamiensis sp. nov., and
      provide data on its distribution, morphology, genetics, ecology and behavior. C.
      lomamiensis is restricted to the lowland rain forests of central DRC between the
      middle Lomami and the upper Tshuapa Rivers. Morphological and molecular data
      confirm that C. lomamiensis is distinct from its nearest congener, C. hamlyni,
      from which it is separated geographically by both the Congo (Lualaba) and the
      Lomami Rivers. C. lomamiensis, like C. hamlyni, is semi-terrestrial with a diet
      containing terrestrial herbaceous vegetation. The discovery of C. lomamiensis
      highlights the biogeographic significance and importance for conservation of
      central Congo's interfluvial TL2 region, defined from the upper Tshuapa River
      through the Lomami Basin to the Congo (Lualaba) River. The TL2 region has been
      found to contain a high diversity of anthropoid primates including three forms,
      in addition to C. lomamiensis, that are endemic to the area. We recommend the
      common name, lesula, for this new species, as it is the vernacular name used over
      most of its known range.

PMID- 22984484
TI  - Transparent soil for imaging the rhizosphere.
AB  - Understanding of soil processes is essential for addressing the global issues of
      food security, disease transmission and climate change. However, techniques for
      observing soil biology are lacking. We present a heterogeneous, porous,
      transparent substrate for in situ 3D imaging of living plants and root-associated
      microorganisms using particles of the transparent polymer, Nafion, and a solution
      with matching optical properties. Minerals and fluorescent dyes were adsorbed
      onto the Nafion particles for nutrient supply and imaging of pore size and
      geometry. Plant growth in transparent soil was similar to that in soil. We imaged
      colonization of lettuce roots by the human bacterial pathogen Escherichia coli
      O157:H7 showing micro-colony development. Micro-colonies may contribute to
      bacterial survival in soil. Transparent soil has applications in root biology,
      crop genetics and soil microbiology.

PMID- 22984483
TI  - Why most biomedical findings echoed by newspapers turn out to be false: the case
      of attention deficit hyperactivity disorder.
AB  - CONTEXT: Because positive biomedical observations are more often published than
      those reporting no effect, initial observations are often refuted or attenuated
      by subsequent studies. OBJECTIVE: To determine whether newspapers preferentially
      report on initial findings and whether they also report on subsequent studies.
      METHODS: We focused on attention deficit hyperactivity disorder (ADHD). Using
      Factiva and PubMed databases, we identified 47 scientific publications on ADHD
      published in the 1990s and soon echoed by 347 newspapers articles. We selected
      the ten most echoed publications and collected all their relevant subsequent
      studies until 2011. We checked whether findings reported in each "top 10"
      publication were consistent with previous and subsequent observations. We also
      compared the newspaper coverage of the "top 10" publications to that of their
      related scientific studies. RESULTS: Seven of the "top 10" publications were
      initial studies and the conclusions in six of them were either refuted or
      strongly attenuated subsequently. The seventh was not confirmed or refuted, but
      its main conclusion appears unlikely. Among the three "top 10" that were not
      initial studies, two were confirmed subsequently and the third was attenuated.
      The newspaper coverage of the "top 10" publications (223 articles) was much
      larger than that of the 67 related studies (57 articles). Moreover, only one of
      the latter newspaper articles reported that the corresponding "top 10" finding
      had been attenuated. The average impact factor of the scientific journals
      publishing studies echoed by newspapers (17.1 n = 56) was higher (p<0.0001) than
      that corresponding to related publications that were not echoed (6.4 n = 56).
      CONCLUSION: Because newspapers preferentially echo initial ADHD findings
      appearing in prominent journals, they report on uncertain findings that are often
      refuted or attenuated by subsequent studies. If this media reporting bias
      generalizes to health sciences, it represents a major cause of distortion in
      health science communication.

PMID- 22984485
TI  - The forgotten role of alcohol: a systematic review and meta-analysis of the
      clinical efficacy and perceived role of chlorhexidine in skin antisepsis.
AB  - BACKGROUND: Skin antisepsis is a simple and effective measure to prevent
      infections. The efficacy of chlorhexidine is actively discussed in the literature
      on skin antisepsis. However, study outcomes due to chlorhexidine-alcohol
      combinations are often attributed to chlorhexidine alone. Thus, we sought to
      review the efficacy of chlorhexidine for skin antisepsis and the extent of a
      possible misinterpretation of evidence. METHODS: We performed a systematic
      literature review of clinical trials and systematic reviews investigating
      chlorhexidine compounds for blood culture collection, vascular catheter insertion
      and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library,
      the Agency for Healthcare Research and Quality website, several clinical trials
      registries and a manufacturer website. We extracted data on study design,
      antiseptic composition, and the following outcomes: blood culture contamination,
      catheter colonisation, catheter-related bloodstream infection and surgical site
      infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine
      compounds and reviewed the appropriateness of the authors' attribution. RESULTS:
      In all three application areas and for all outcomes, we found good evidence
      favouring chlorhexidine-alcohol over aqueous competitors, but not over
      competitors combined with alcohols. For blood cultures and surgery, we found no
      evidence supporting chlorhexidine alone. For catheters, we found evidence in
      support of chlorhexidine alone for preventing catheter colonisation, but not for
      preventing bloodstream infection. A range of 29 to 43% of articles attributed
      outcomes solely to chlorhexidine when the combination with alcohol was in fact
      used. Articles with ambiguous attribution were common (8-35%). Unsubstantiated
      recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were
      identified in several practice recommendations and evidence-based guidelines.
      CONCLUSIONS: Perceived efficacy of chlorhexidine is often in fact based on
      evidence for the efficacy of the chlorhexidine-alcohol combination. The role of
      alcohol has frequently been overlooked in evidence assessments. This has broader
      implications for knowledge translation as well as potential implications for
      patient safety.

PMID- 22984487
TI  - Efficient antifouling surface for quantitative surface plasmon resonance based
      biosensor analysis.
AB  - Non-specific binding to biosensor surfaces is a major obstacle to quantitative
      analysis of selective retention of analytes at immobilized target molecules.
      Although a range of chemical antifouling monolayers has been developed to address
      this problem, many macromolecular interactions still remain refractive to
      analysis due to the prevalent high degree of non-specific binding. In this
      manuscript we explore the dynamic process of the formation of self-assembled
      monolayers and optimize physical and chemical properties thus reducing
      considerably non-specific binding while maintaining the integrity of the
      immobilized biomolecules. As a result, analysis of specific binding of analytes
      to immobilized target molecules is significantly facilitated.

PMID- 22984486
TI  - Evaluation of the ISO standard 11063 DNA extraction procedure for assessing soil
      microbial abundance and community structure.
AB  - Soil DNA extraction has become a critical step in describing microbial
      biodiversity. Historically, ascertaining overarching microbial ecological
      theories has been hindered as independent studies have used numerous custom and
      commercial DNA extraction procedures. For that reason, a standardized soil DNA
      extraction method (ISO-11063) was previously published. However, although this
      ISO method is suited for molecular tools such as quantitative PCR and community
      fingerprinting techniques, it has only been optimized for examining soil
      bacteria. Therefore, the aim of this study was to assess an appropriate soil DNA
      extraction procedure for examining bacterial, archaeal and fungal diversity in
      soils of contrasting land-use and physico-chemical properties. Three different
      procedures were tested: the ISO-11063 standard; a custom procedure (GnS-GII); and
      a modified ISO procedure (ISOm) which includes a different mechanical lysis step
      (a FastPrep (r)-24 lysis step instead of the recommended bead-beating). The
      efficacy of each method was first assessed by estimating microbial biomass
      through total DNA quantification. Then, the abundances and community structure of
      bacteria, archaea and fungi were determined using real-time PCR and terminal
      restriction fragment length polymorphism approaches. Results showed that DNA
      yield was improved with the GnS-GII and ISOm procedures, and fungal community
      patterns were found to be strongly dependent on the extraction method. The main
      methodological factor responsible for differences between extraction procedure
      efficiencies was found to be the soil homogenization step. For integrative
      studies which aim to examine bacteria, archaea and fungi simultaneously, the ISOm
      procedure results in higher DNA recovery and better represents microbial
      communities.

PMID- 22984488
TI  - Active collisions in altered gravity reveal eye-hand coordination strategies.
AB  - Most object manipulation tasks involve a series of actions demarcated by
      mechanical contact events, and gaze is usually directed to the locations of these
      events as the task unfolds. Typically, gaze foveates the target 200 ms in advance
      of the contact. This strategy improves manual accuracy through visual feedback
      and the use of gaze-related signals to guide the hand/object. Many studies have
      investigated eye-hand coordination in experimental and natural tasks; most of
      them highlighted a strong link between eye movements and hand or object
      kinematics. In this experiment, we analyzed gaze strategies in a collision task
      but in a very challenging dynamical context. Participants performed collisions
      while they were exposed to alternating episodes of microgravity, hypergravity and
      normal gravity. First, by isolating the effects of inertia in microgravity, we
      found that peak hand acceleration marked the transition between two modes of grip
      force control. Participants exerted grip forces that paralleled load force
      profiles, and then increased grip up to a maximum shifted after the collision.
      Second, we found that the oculomotor strategy adapted visual feedback of the
      controlled object around the collision, as demonstrated by longer durations of
      fixation after collision in new gravitational environments. Finally, despite
      large variability of arm dynamics in altered gravity, we found that saccades were
      remarkably time-locked to the peak hand acceleration in all conditions. In
      conclusion, altered gravity allowed light to be shed on predictive mechanisms
      used by the central nervous system to coordinate gaze, hand and grip motor
      actions during a mixed task that involved transport of an object and high impact
      loads.

PMID- 22984489
TI  - New strain of simian immunodeficiency virus identified in wild-born chimpanzees
      from central Africa.
AB  - Studies of primate lentiviruses continue to provide information about the
      evolution of simian immunodeficiency viruses (SIVs) and the origin and emergence
      of HIV since chimpanzees in west-central Africa (Pan troglodytes troglodytes)
      were recognized as the reservoir of SIVcpzPtt viruses, which have been related
      phylogenetically to HIV-1. Using in-house peptide ELISAs to study SIV prevalence,
      we tested 104 wild-born captive chimpanzees from Gabon and Congo. We identified
      two new cases of SIVcpz infection in Gabon and characterized a new SIVcpz strain,
      SIVcpzPtt-Gab4. The complete sequence (9093 bp) was obtained by a PCR-based
      'genome walking' approach to generate 17 overlapping fragments. Phylogenetic
      analyses of separated genes (gag, pol-vif and env-nef) showed that SIVcpzPtt-Gab4
      is closely related to SIVcpzPtt-Gab1 and SIVcpzPtt-Gab2. No significant variation
      in viral load was observed during 3 years of follow-up, but a significantly lower
      CD4+ T cells count was found in infected than in uninfected chimpanzees (p<0.05).
      No clinical symptoms of SIV infection were observed in the SIV-positive
      chimpanzees. Further field studies with non-invasive methods are needed to
      determine the prevalence, geographic distribution, species association, and
      natural history of SIVcpz strains in the chimpanzee habitat in Gabon.

PMID- 22984490
TI  - Development and validation of a new questionnaire assessing quality of life in
      adults with hypopituitarism: Adult Hypopituitarism Questionnaire (AHQ).
AB  - OBJECTIVE: To develop and validate the Adult Hypopituitarism Questionnaire (AHQ)
      as a disease-specific, self-administered questionnaire for evaluation of quality
      of life (QOL) in adult patients with hypopituitarism. METHODS: We developed and
      validated this new questionnaire, using a standardized procedure which included
      item development, pilot-testing and psychometric validation. Of the patients who
      participated in psychometric validation, those whose clinical conditions were
      judged to be stable were asked to answer the survey questionnaire twice, in order
      to assess test-retest reliability. RESULTS: Content validity of the initial
      questionnaire was evaluated via two pilot tests. After these tests, we made minor
      revisions and finalized the initial version of the questionnaire. The
      questionnaire was constructed with two domains, one psycho-social and the other
      physical. For psychometric assessment, analyses were performed on the responses
      of 192 adult patients with various types of hypopituitarism. The intraclass
      correlations of the respective domains were 0.91 and 0.95, and the Cronbach's
      alpha coefficients were 0.96 and 0.95, indicating adequate test-retest
      reliability and internal consistency for each domain. For known-group validity,
      patients with hypopituitarism due to hypothalamic disorder showed significantly
      lower scores in 11 out of 13 sub-domains compared to those who had
      hypopituitarism due to pituitary disorder. Regarding construct validity, the
      domain structure was found to be almost the same as that initially hypothesized.
      Exploratory factor analysis (n = 228) demonstrated that each domain consisted of
      six and seven sub-domains. CONCLUSION: The AHQ showed good reliability and
      validity for evaluating QOL in adult patients with hypopituitarism.

PMID- 22984491
TI  - Apoptotic phosphorylation of histone H3 on Ser-10 by protein kinase Cdelta.
AB  - Phosphorylation of histone H3 on Ser-10 is regarded as an epigenetic mitotic
      marker and is tightly correlated with chromosome condensation during both mitosis
      and meiosis. However, it was also reported that histone H3 Ser-10 phosphorylation
      occurs when cells are exposed to various death stimuli, suggesting a potential
      role in the regulation of apoptosis. Here we report that histone H3 Ser-10
      phosphorylation is mediated by the pro-apoptotic kinase protein kinase C (PKC)
      delta during apoptosis. We observed that PKCdelta robustly phosphorylates histone
      H3 on Ser-10 both in vitro and in vivo. Ectopic expression of catalytically
      active PKCdelta efficiently induces condensed chromatin structure in the nucleus.
      We also discovered that activation of PKCdelta is required for histone H3 Ser-10
      phosphorylation after treatment with DNA damaging agents during apoptosis.
      Collectively, these findings suggest that PKCdelta is the kinase responsible for
      histone H3 Ser-10 phosphoryation during apoptosis and thus contributes to
      chromatin condensation together with other apoptosis-related histone
      modifications. As a result, histone H3 Ser-10 phosphorylation can be designated a
      new 'apoptotic histone code' mediated by PKCdelta.

PMID- 22984492
TI  - Sub-domains of ricin's B subunit as targets of toxin neutralizing and non
      neutralizing monoclonal antibodies.
AB  - The B subunit (RTB) of ricin toxin is a galactose (Gal)-/N-acetylgalactosamine
      (GalNac)-specific lectin that mediates attachment, entry, and intracellular
      trafficking of ricin in host cells. Structurally, RTB consists of two globular
      domains with identical folding topologies. Domains 1 and 2 are each comprised of
      three homologous sub-domains (alpha, beta, gamma) that likely arose by gene
      duplication from a primordial carbohydrate recognition domain (CRD), although
      only sub-domains 1alpha and 2gamma retain functional lectin activity. As part of
      our ongoing effort to generate a comprehensive B cell epitope map of ricin, we
      report the characterization of three new RTB-specific monoclonal antibodies
      (mAbs). All three mAbs, JB4, B/J F9 and C/M A2, were initially identified based
      on their abilities to neutralize ricin in a Vero cell cytotoxicity assay and to
      partially (or completely) block ricin attachment to cell surfaces. However, only
      JB4 proved capable of neutralizing ricin in a macrophage apoptosis assay and in
      imparting passive immunity to mice in a model of systemic intoxication. Using a
      combination of techniques, including competitive ELISAs, pepscan analysis,
      differential reactivity by Western blot, as well as affinity enrichment of phage
      displayed peptides, we tentatively localized the epitopes recognized by the non
      neutralizing mAbs B/J F9 and C/M A2 to sub-domains 2alpha and 2beta,
      respectively. Furthermore, we propose that the epitope recognized by JB4 is
      within sub-domain 2gamma, adjacent to RTB's high affinity Gal/GalNAc CRD. These
      data suggest that recognition of RTB's sub-domains 1alpha and 2gamma are critical
      determinants of antibody neutralizing activity and protective immunity to ricin.

PMID- 22984493
TI  - Characterization of rheumatoid arthritis subtypes using symptom profiles,
      clinical chemistry and metabolomics measurements.
AB  - OBJECTIVE: The aim is to characterize subgroups or phenotypes of rheumatoid
      arthritis (RA) patients using a systems biology approach. The discovery of
      subtypes of rheumatoid arthritis patients is an essential research area for the
      improvement of response to therapy and the development of personalized medicine
      strategies. METHODS: In this study, 39 RA patients are phenotyped using clinical
      chemistry measurements, urine and plasma metabolomics analysis and symptom
      profiles. In addition, a Chinese medicine expert classified each RA patient as a
      Cold or Heat type according to Chinese medicine theory. Multivariate data
      analysis techniques are employed to detect and validate biochemical and symptom
      relationships with the classification. RESULTS: The questionnaire items 'Red
      joints', 'Swollen joints', 'Warm joints' suggest differences in the level of
      inflammation between the groups although c-reactive protein (CRP) and rheumatoid
      factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics
      data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than
      in the Heat RA patients, suggesting differences in muscle breakdown.
      Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat
      patients compared to Cold patients were found suggesting that the Cold RA group
      has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function.
      CONCLUSION: Significant and relevant biochemical differences are found between
      Cold and Heat RA patients. Differences in immune function, HPA axis involvement
      and muscle breakdown point towards opportunities to tailor disease management
      strategies to each of the subgroups RA patient.

PMID- 22984494
TI  - Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by
      nevirapine in vitro.
AB  - Since the antiretroviral therapy (ART) was introduced to patients infected by
      human immunodeficiency virus (HIV), the HIV related mortality and morbidity have
      been significantly reduced. The major obstacle for long-term successful anti-HIV
      treatment is the emergence of drug resistant mutants. Current data of drug
      resistance was mainly obtained on HIV-1 subtype B but rarely on non-B virus, even
      more rare with newly emerged circulating recombinant forms (CRFs). The lack of
      such data limits the rational management of ART for the increasing number of
      patients infected by non-subtype B virus. In this study, a HIV-1 CRF07_BC strain
      CNGZD was isolated from a HIV patient and its genome was sequenced and deposited
      in GenBank (JQ423923). Potential drug resistant mutants of this CRF07_BC virus
      strain were selected in PBMCs cultures in the presence of Nevirapine (NVP), which
      is the most frequently used antiretroviral drug in China. Four combination
      profiles of mutations were identified in the NVP-selected mutants, which were
      initiated with A98G, V108I, Y181C and I135T/I382L and followed by more than two
      other mutations at the end of the selections, respectively. A total of seven
      previously reported mutations (A98G, V106M, V108I, I135T, Y181C, V189I, K238N)
      and seven novel mutations (P4H, T48I, I178M, V314A, I382L/V, T386A) in the
      reverse transcriptase gene were found in these NVP-selected mutants. Phenotypic
      analysis in the NVP-selected mutants showed that all the mutations, except P4H,
      contribute to NVP resistance. Among them, V106M and Y181C reduce NVP
      susceptibility for more than 20-fold, while the other mutations cause less than
      20 folds drug resistance. Although the information obtained in this in vitro
      selection study may not fully cover resistant mutations which will actually occur
      in patients, it has still provided useful information for rational management of
      ART in patients infected with HIV CRF_BC subtype.

PMID- 22984495
TI  - Women up, men down: the clinical impact of replacing the Framingham Risk Score
      with the Reynolds Risk Score in the United States population.
AB  - BACKGROUND: The Reynolds Risk Score (RRS) is one alternative to the Framingham
      Risk Score (FRS) for cardiovascular risk assessment. The Adult Treatment Panel
      III (ATP III) integrated the FRS a decade ago, but with the anticipated release
      of ATP IV, it remains uncertain how and which risk models will be integrated into
      the recommendations. We sought to define the effects in the United States
      population of a transition from the FRS to the RRS for cardiovascular risk
      assessment. METHODS: Using the National Health and Nutrition Examination Surveys,
      we assessed FRS and RRS in 2,502 subjects representing approximately 53.6 Million
      (M) men (ages 50-79) and women (ages 45-79), without cardiovascular disease or
      diabetes. We calculated the proportion reclassified by RRS and the subset whose
      LDL-C goal achievement changed. RESULTS: Compared to FRS, the RRS assigns a
      higher risk category to 13.9% of women and 9.1% of men while assigning a lower
      risk to 35.7% of men and 2% of women. Overall, 4.7% of women and 1.1% of men fail
      to meet newly intensified LDL-C goals using the RRS. Conversely, 10.5% of men and
      0.6% of women now meet LDL-C goal using RRS when they had not by FRS. CONCLUSION:
      In the U.S. population the RRS assigns a new risk category for one in six women
      and four of nine men. In general, women increase while men decrease risk. In
      conclusion, adopting the RRS for the 53.6 million eligible U.S. adults would
      result in intensification of clinical management in 1.6 M additional women and
      2.10 M fewer men.

PMID- 22984496
TI  - Characterization of an AGAMOUS-like MADS box protein, a probable constituent of
      flowering and fruit ripening regulatory system in banana.
AB  - The MADS-box family of genes has been shown to play a significant role in the
      development of reproductive organs, including dry and fleshy fruits. In this
      study, the molecular properties of an AGAMOUS like MADS box transcription factor
      in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has
      been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box
      protein in banana flower and fruit nuclear extracts in DNA-protein interaction
      assays. The protein fraction in the DNA-protein complex was analyzed by mass
      spectrometry and using this information we have obtained the full length cDNA of
      the corresponding protein. The deduced protein sequence showed ~95% amino acid
      sequence homology with MA-MADS5, a MADS-box protein described previously from
      banana. We have characterized the domains of the identified AGAMOUS MADS-box
      protein involved in DNA binding and homodimer formation in vitro using full
      length and truncated versions of affinity purified recombinant proteins.
      Furthermore, in order to gain insight about how DNA bending is achieved by this
      MADS-box factor, we performed circular permutation and phasing analysis using the
      wild type recombinant protein. The AGAMOUS MADS-box protein identified in this
      study has been found to predominantly accumulate in the climacteric fruit pulp
      and also in female flower ovary. In vivo and in vitro assays have revealed
      specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence
      in the promoters of major ripening genes in banana fruit. Overall, the expression
      patterns of this MADS-box protein in banana female flower ovary and during
      various phases of fruit ripening along with the interaction of the protein to the
      CArG-box sequence in the promoters of major ripening genes lead to interesting
      assumption about the possible involvement of this AGAMOUS MADS-box factor in
      banana fruit ripening and floral reproductive organ development.

PMID- 22984497
TI  - A general HIV incidence inference scheme based on likelihood of individual level
      data and a population renewal equation.
AB  - We derive a new method to estimate the age specific incidence of an infection
      with a differential mortality, using individual level infection status data from
      successive surveys. The method consists of a) an SI-type model to express the
      incidence rate in terms of the prevalence and its derivatives as well as the
      difference in mortality rate, and b) a maximum likelihood approach to estimate
      the prevalence and its derivatives. Estimates can in principle be obtained for
      any chosen age and time, and no particular assumptions are made about the
      epidemiological or demographic context. This is in contrast with earlier methods
      for estimating incidence from prevalence data, which work with aggregated data,
      and the aggregated effect of demographic and epidemiological rates over the time
      interval between prevalence surveys. Numerical simulation of HIV epidemics, under
      the presumption of known excess mortality due to infection, shows improved
      control of bias and variance, compared to previous methods. Our analysis
      motivates for a) effort to be applied to obtain accurate estimates of excess
      mortality rates as a function of age and time among HIV infected individuals and
      b) use of individual level rather than aggregated data in order to estimate HIV
      incidence rates at times between two prevalence surveys.

PMID- 22984498
TI  - The prothrombotic phenotypes in familial protein C deficiency are differentiated
      by computational modeling of thrombin generation.
AB  - The underlying cause of thrombosis in a large protein C (PC) deficient Vermont
      kindred appears to be multicausal and not explained by PC deficiency alone. We
      evaluated the contribution of coagulation factors to thrombin generation in this
      population utilizing a mathematical model that incorporates a mechanistic
      description of the PC pathway. Thrombin generation profiles for each individual
      were generated with and without the contribution of the PC pathway. Parameters
      that describe thrombin generation: maximum level (MaxL) and rate (MaxR), their
      respective times (TMaxL, TMaxR), area under the curve (AUC) and clotting time
      (CT) were examined in individuals +/- PC mutation, +/- prothrombin G20210A
      polymorphism and +/- thrombosis history (DVT or PE). This family (n = 364) is
      shifted towards greater thrombin generation relative to the mean physiologic
      control. When this family was analyzed with the PC pathway, our results showed
      that: carriers of the PC mutation (n = 81) had higher MaxL and MaxR and greater
      AUC (all p<0.001) than non-carriers (n = 283); and individuals with a DVT and/or
      PE history (n = 13) had higher MaxL (p = 0.005) and greater AUC (p<0.001) than
      individuals without a thrombosis history (n = 351). These differences were
      further stratified by gender, with women in all categories generating more
      thrombin than males. These results show that all individuals within this family
      with or without PC deficiency have an increased baseline procoagulant potential
      reflective of increased thrombin generation. In addition, variations within the
      plasma composition of each individual can further segregate out increased
      procoagulant phenotypes, with gender-associated plasma compositional differences
      playing a large role.

PMID- 22984499
TI  - Maize benefits the predatory beetle, Propylea japonica (Thunberg), to provide
      potential to enhance biological control for aphids in cotton.
AB  - BACKGROUND: Biological control provided by natural enemies play an important role
      in integrated pest management. Generalist insect predators provide an important
      biological service in the regulation of agricultural insect pests. Our goal is to
      understand the explicit process of oviposition preference, habitat selection and
      feeding behavior of predators in farmland ecosystem consisting of multiple crops,
      which is central to devising and delivering an integrated pest management
      program. METHODOLOGY: The hypotheses was that maize can serve as habitat for
      natural enemies and benefits predators to provide potential to enhance biological
      control for pest insects in cotton. This explicit process of a predatory beetle,
      Propylea japonica, in agricultural ecosystem composed of cotton and maize were
      examined by field investigation and stable carbon isotope analysis during 2008
      2010. PRINCIPAL FINDING: Field investigation showed that P. japonica adults will
      search host plants for high prey abundance before laying eggs, indicating
      indirectly that P. japonica adults prefer to inhabit maize plants and travel to
      cotton plants to actively prey on aphids. The delta(13)C values of adult P.
      japonica in a dietary shift experiment found that individual beetles were
      shifting from a C(3)- to a C(4)-based diet of aphids reared on maize or cotton,
      respectively, and began to reflect the isotope ratio of their new C(4) resources
      within one week. Approximately 80-100% of the diet of P. japonica adults in maize
      originated from a C(3)-based resource in June, July and August, while
      approximately 80% of the diet originated from a C(4)-based resource in September.
      CONCLUSION/SIGNIFICANCE: Results suggest that maize can serve as a habitat or
      refuge source for the predatory beetle, P. japonica, and benefits predators to
      provide potential to enhance biological control for insect pests in cotton.

PMID- 22984500
TI  - Association of single nucleotide polymorphisms of IL23R and IL17 with ulcerative
      colitis risk in a Chinese Han population.
AB  - BACKGROUND: Previous studies implicated that IL23R and IL17 genes play an
      important role in autoimmune inflammation. Genome-wide association studies have
      also identified multiple single nucleotide polymorphisms (SNPs) in the IL23R gene
      region associated with inflammatory bowel diseases. This study examined the
      association of IL23R and IL17A gene SNPs with ulcerative colitis susceptibility
      in a population in China. METHODOLOGY: A total of 270 ulcerative colitis and 268
      healthy controls were recruited for the analyses of 23 SNPs in the IL23R and
      IL17A regions. Genomic DNA was extracted and analysis of these 23 SNPs using
      ligase detection reaction allelic (LDR) technology. Genotype and allele
      associations were calculated using SPSS 13.0 software package. PRINCIPAL
      FINDINGS: Compared to the healthy controls, the variant alleles IL23R rs7530511,
      and rs11805303 showed a statistically significant difference for ulcerative
      colitis susceptibility (0.7% vs 3.3%, P = 0.002; 60.4% vs 53.2%, P = 0.0017,
      respectively). The linkage disequilibrium (LD) patterns of these SNPs were
      measured and three LD blocks from the SNPs of IL23R and one block from those of
      IL17A were identified. A novel association with ulcerative colitis susceptibility
      occurred in haplotypes of IL23R (Block1 H3 P = 0.02; Block2 H2 P = 0.019; Block3
      H4 P = 0.029) and IL17A (H4 P = 0.034). Pair-wise analyses showed an interaction
      between the risk haplotypes in IL23R and IL17A (P = 0.014). CONCLUSIONS: Our
      study demonstrated that rs7530511, and rs11805303 of IL23R were significantly
      associated with ulcerative colitis susceptibility in the Chinese population. The
      most noticeable finding was the linkage of IL23R and IL17A gene region to
      ulcerative colitis risk due to the gene-gene interaction.

PMID- 22984502
TI  - Predicting the fate of biodiversity using species' distribution models: enhancing
      model comparability and repeatability.
AB  - Species distribution modeling (SDM) is an increasingly important tool to predict
      the geographic distribution of species. Even though many problems associated with
      this method have been highlighted and solutions have been proposed, little has
      been done to increase comparability among studies. We reviewed recent
      publications applying SDMs and found that seventy nine percent failed to report
      methods that ensure comparability among studies, such as disclosing the maximum
      probability range produced by the models and reporting on the number of species
      occurrences used. We modeled six species of Falco from northern Europe and
      demonstrate that model results are altered by (1) spatial bias in species'
      occurrence data, (2) differences in the geographic extent of the environmental
      data, and (3) the effects of transformation of model output to presence/absence
      data when applying thresholds. Depending on the modeling decisions, forecasts of
      the future geographic distribution of Falco ranged from range contraction in 80%
      of the species to no net loss in any species, with the best model predicting no
      net loss of habitat in Northern Europe. The fact that predictions of range
      changes in response to climate change in published studies may be influenced by
      decisions in the modeling process seriously hampers the possibility of making
      sound management recommendations. Thus, each of the decisions made in generating
      SDMs should be reported and evaluated to ensure conclusions and policies are
      based on the biology and ecology of the species being modeled.

PMID- 22984501
TI  - Population dynamics and genetic diversity of C4 strains of human enterovirus 71
      in Mainland China, 1998-2010.
AB  - BACKGROUND: Since 1997, several countries within the Asian Pacific region have
      been affected by one or more massive outbreaks of Hand Foot and Mouth Disease
      (HFMD). Virus typing experiments revealed that these outbreaks were caused by
      strains of human enterovirus 71 (EV71) belonging to several different, recently
      emerged subgenogroups. In mainland China, a different situation was observed. The
      first outbreak, localized in Shangdong Province, was reported in 2007, and was
      followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers
      of reported HFMD cases have been persistently high. METHODOLOGY/PRINCIPAL
      FINDINGS: To gain insight in the epidemiological behavior of EV71 in China, we
      studied genetic diversity and EV71 population dynamics to address whether the
      increase in number of reported EV71 infections reflects a real increase in viral
      spread or is just the result of increased awareness and surveillance. We used
      systematically collected VP1 gene sequences of 257 EV71 strains collected in
      Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and
      supplemented them with 305 GenBank EV71 reference stains collected in China from
      1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4.
      Viral population dynamics indicated that the increased reporting of HFMD in China
      since 2007 reflects a real increase in viral spread and continued replacement of
      viral lineages through time. Amino acid sequence comparisons revealed
      substitution of amino acid in residues 22, 145 and 289 through time regularly
      with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010.
      CONCLUSIONS: EV71 strains isolated in mainland China mainly belonged to
      subgenogroup C4. There was exponential growth of the EV71 virus population in
      2007 and 2008. There was amino acid substitution through time regularly with the
      VP1 gene which possibly increased viral spread and/or ability of the virus to
      circulate persistently among the Chinese population.

PMID- 22984503
TI  - Sexual selection of human cooperative behaviour: an experimental study in rural
      Senegal.
AB  - Human cooperation in large groups and between non-kin individuals remains a
      Darwinian puzzle. Investigations into whether and how sexual selection is
      involved in the evolution of cooperation represent a new and important research
      direction. Here, 69 groups of four men or four women recruited from a rural
      population in Senegal played a sequential public-good game in the presence of out
      group observers, either of the same sex or of the opposite sex. At the end of the
      game, participants could donate part of their gain to the village school in the
      presence of the same observers. Both contributions to the public good and
      donations to the school, which reflect different components of cooperativeness,
      were influenced by the sex of the observers. The results suggest that in this non
      Western population, sexual selection acts mainly on men's cooperative behaviour
      with non-kin, whereas women's cooperativeness is mainly influenced by nonsexual
      social selection.

PMID- 22984504
TI  - Affective and neural reactivity to criticism in individuals high and low on
      perceived criticism.
AB  - People who have remitted from depression are at increased risk for relapse if
      they rate their relatives as being critical of them on a simple self-report
      measure of Perceived Criticism (PC). To explore neural mechanisms associated with
      this we used functional magnetic resonance imaging (fMRI) to examine how people
      with different levels of PC responded to hearing criticism from their own
      mothers. To maximize variability in affective reactivity, depressed, recovered
      depressed, and healthy control participants (n = 33) were classified as high or
      low in PC based on a median split. They were then exposed to personally-relevant
      critical and praising comments from their mothers. Perceived Criticism levels
      were unrelated to depression status and to negative mood change after hearing
      criticism. However, compared to low PC participants, those who scored high on PC
      showed differential activation in a network of regions associated with emotion
      reactivity and regulation, including increased amygdala activity and decreased
      reactions in prefrontal regulatory regions when they heard criticism. This was
      not the case for praise. Criticism may be a risk factor for relapse because it
      helps to "train" pathways characteristic of depressive information processing.
      The Perceived Criticism measure may help identify people who are more susceptible
      to this vulnerability.

PMID- 22984505
TI  - FH535 inhibited migration and growth of breast cancer cells.
AB  - There is substantial evidence indicating that the WNT signaling pathway is
      activated in various cancer cell types including breast cancer. Previous studies
      reported that FH535, a small molecule inhibitor of the WNT signaling pathway,
      decreased growth of cancer cells but not normal fibroblasts, suggesting this
      pathway plays a role in tumor progression and metastasis. In this study, we
      tested FH535 as a potential inhibitor for malignant phenotypes of breast cancer
      cells including migration, invasion, and growth. FH535 significantly inhibited
      growth, migration, and invasion of triple negative (TN) breast cancer cell lines
      (MDA-MB231 and HCC38) in vitro. We demonstrate that FH535 was a potent growth
      inhibitor for TN breast cancer cell lines (HCC38 and MDA-MB-231) but not for
      other, non-TN breast cancer cell lines (MCF-7, T47D or SK-Br3) when cultured in
      three dimensional (3D) type I collagen gels. Western blotting analyses suggest
      that treatment of MDA-MB-231 cells with FH535 markedly inhibited the expression
      of NEDD9 but not activations of FAK, Src, or downstream targets such as p38 and
      Erk1/2. We demonstrated that NEDD9 was specifically associated with CSPG4 but not
      with beta1 integrin or CD44 in MDA-MB-231 cells. Analyses of gene expression
      profiles in breast cancer tissues suggest that CSPG4 expression is higher in
      Basal-type breast cancers, many of which are TN, than any other subtypes. These
      results suggest not only a mechanism for migration and invasion involving the
      canonical WNT-signaling pathways but also novel strategies for treating patients
      who develop TN breast cancer.

PMID- 22984507
TI  - A European melting pot of harbour porpoise in the French Atlantic coasts inferred
      from mitochondrial and nuclear data.
AB  - Field surveys have reported a global shift in harbour porpoise distribution in
      European waters during the last 15 years, including a return to the Atlantic
      coasts of France. In this study, we analyzed genetic polymorphisms at a fragment
      of the mitochondrial control region (mtDNA CR) and 7 nuclear microsatellite loci,
      for 52 animals stranded and by-caught between 2000 and 2010 along the Atlantic
      coasts of France. The analysis of nuclear and mitochondrial loci provided
      contrasting results. The mtDNA revealed two genetically distinct groups, one
      closely related to the Iberian and African harbour porpoises, and the second
      related to individuals from the more northern waters of Europe. In contrast,
      nuclear polymorphisms did not display such a distinction. Nuclear markers
      suggested that harbour porpoises behaved as a randomly mating population along
      the Atlantic coasts of France. The difference between the two kinds of markers
      can be explained by differences in their mode of inheritance, the mtDNA being
      maternally inherited in contrast to nuclear loci that are bi-parentally
      inherited. Our results provide evidence that a major proportion of the animals we
      sampled are admixed individuals from the two genetically distinct populations
      previously identified along the Iberian coasts and in the North East Atlantic.
      The French Atlantic coasts are clearly the place where these two previously
      separated populations of harbour porpoises are now admixing. The present shifts
      in distribution of harbour porpoises along this coast is likely caused by habitat
      changes that will need to be further studied.

PMID- 22984508
TI  - Amino acids and TOR signaling promote prothoracic gland growth and the initiation
      of larval molts in the tobacco hornworm Manduca sexta.
AB  - Molting in arthropods is orchestrated by a series of endocrine changes that occur
      towards the end of an instar. However, little is understood about the mechanisms
      that trigger these endocrine changes. Here, nutritional inputs were manipulated
      to investigate the minimal nutritional inputs required for a Manduca sexta larva
      to initiate a molt. Amino acids were found to be necessary for a larva to molt,
      indicating the involvement of an amino acid sensitive pathway. Feeding rapamycin,
      an inhibitor of the target of rapamycin (TOR) signaling, delayed the onset of a
      molt and resulted in abnormally larger larvae. Rapamycin also suppressed the
      growth of the prothoracic glands relative to the whole body growth, and this was
      accompanied by suppression of ecdysone production and secretion. Higher doses of
      rapamycin also slowed the growth rate, indicating that TOR signaling also plays a
      role in systemic growth. TOR signaling therefore couples the nutritional status
      of the larva to the endocrine system to regulate the timing of a molt.

PMID- 22984510
TI  - Evolving righteousness in a corrupt world.
AB  - Punishment offers a powerful mechanism for the maintenance of cooperation in
      human and animal societies, but the maintenance of costly punishment itself
      remains problematic. Game theory has shown that corruption, where punishers can
      defect without being punished themselves, may sustain cooperation. However, in
      many human societies and some insect ones, high levels of cooperation coexist
      with low levels of corruption, and such societies show greater wellbeing than
      societies with high corruption. Here we show that small payments from cooperators
      to punishers can destabilize corrupt societies and lead to the spread of
      punishment without corruption (righteousness). Righteousness can prevail even in
      the face of persistent power inequalities. The resultant righteous societies are
      highly stable and have higher wellbeing than corrupt ones. This result may help
      to explain the persistence of costly punishing behavior, and indicates that
      corruption is a sub-optimal tool for maintaining cooperation in human societies.

PMID- 22984509
TI  - Apolipoprotein E4 is deficient in inducing macrophage ABCA1 expression and
      stimulating the Sp1 signaling pathway.
AB  - ATP binding cassette A1 (ABCA1) is a membrane protein that promotes cellular
      cholesterol efflux. Using RAW 264.7 macrophages, we studied the relative effects
      of apolipoprotein (apo) E3 and apoE4 on ABCA1 and on the signaling pathway that
      regulates its expression. Both lipid-associated and lipid-free apoE4 forms
      induced ~30% lower levels of ABCA1 protein and mRNA than apoE3 forms.
      Phosphorylated levels of phosphoinositol 3-kinase (PI3K), protein kinase Czeta
      (PKCzeta) and specificity protein 1 (Sp1) were also lower when treated with apoE4
      compared to apoE3. The reduced ability of apoE4 to induce ABCA1 expression,
      PKCzeta and Sp1 phosphorylation were confirmed in human THP-1
      monocytes/macrophages. Sequential phosphorylation of PI3K, PKCzeta and Sp1 has
      been suggested as a mechanism for upregulation of ABCA1 expression. Both apoE3
      and apoE4 reduced total cholesterol and cholesterol esters in lipid-laden RAW
      264.7 cells, and induced apoAI-mediated cholesterol efflux. However, the
      cholesterol esters and cholesterol efflux in apoE4-treated cells were ~50% and
      ~24% lower, respectively, compared to apoE3-treated cells. Accumulation of
      cholesterol esters in macrophages is a mechanism for foam cell formation. Thus
      the reduced ability of apoE4 to activate the PI3K-PKCzeta-Sp1 signaling pathway
      and induce ABCA1 expression likely impairs cholesterol ester removal, and
      increases foam cell formation.

PMID- 22984511
TI  - X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and
      cervical cancer risk: a huge systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies investigating the association between X-ray repair
      cross-complementation group 1(XRCC1) polymorphisms and cervical cancer (CC) risk
      has provided inconsistent results. The aim of our study was to assess the
      association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms
      and risk of CC. METHODS: Two investigators independently searched the Medline,
      Embase, CNKI, and Chinese Biomedicine Databases for studies published before
      March 2011.Summary odds ratios (ORs) and 95% confidence intervals (CIs) for XRCC1
      polymorphisms and CC were calculated in a fixed-effects model or a random-effects
      model when appropriate. RESULTS: Ultimately, 9, 5 and 2 studies were found to be
      eligible for meta-analyses of Arg399Gln, Arg194Trp and Arg280His, respectively.
      Our analysis suggested that the variant genotypes of Arg194Trp were associated
      with a significantly increased CC risk (Trp/Trp vs Arg/Arg, OR = 2.21, 95% CI =
      1.60-3.06; Arg/Trp vs Arg/Arg, OR = 1.23, 95% CI = 1.02-1.49; dominant model, OR
      = 1.36, 95% CI = 1.14-1.63; recessive model, OR = 2.06, 95% CI = 1.51-2.82). For
      Arg280His polymorphism, no obvious associations were found for all genetic
      models. For Arg399Gln polymorphism, also no obvious associations were found for
      all genetic models. In the subgroup analyses by ethnicity/country, a
      significantly increased risk was observed among Asian, especially among Chinese.
      To get more precise evidences, adjusted ORs (95%CI) by potential confounders
      (such as age, ethnicity or smoking, etc) were also calculated for XRCC1 Arg399Gln
      and Arg194Trp, however, the estimated pooled adjusted OR still did not change at
      all. CONCLUSION: This meta-analysis suggests that Arg194Trp polymorphism may be
      associated with CC risk, Arg399Gln polymorphism might be a low-penetrent risk
      factor for CC only in Asians, and there may be no association between Arg280His
      polymorphism and CC risk.

PMID- 22984512
TI  - Ovulatory shifts in women's attractions to primary partners and other men:
      further evidence of the importance of primary partner sexual attractiveness.
AB  - Previous research has documented shifts in women's attractions to their romantic
      partner and to men other than their partner across the ovulation cycle,
      contingent on the degree to which her partner displays hypothesized indicators of
      high-fitness genes. The current study set out to replicate and extend this
      finding. Forty-one couples in which the woman was naturally cycling participated.
      Female partners reported their feelings of in-pair attraction and extra-pair
      attraction on two occasions, once on a low-fertility day of the cycle and once on
      a high-fertility day of the cycle just prior to ovulation. Ovulation was
      confirmed using luteinizing hormone tests. We collected two measures of male
      partner sexual attractiveness. First, the women in the study rated their
      partner's sexual attractiveness. Second, we photographed the partners and had the
      photos independently rated for attractiveness. Shifts in women's in-pair
      attractions across the cycle were significantly moderated by women's ratings of
      partner sexual attractiveness, such that the less sexually attractive women rated
      their partner, the less in-pair attraction they reported at high fertility
      compared with low fertility (partial r = .37, p(dir) = .01). Shifts in women's
      extra-pair attractions across the cycle were significantly moderated by third
      party ratings of partner attractiveness, such that the less attractive the
      partner was, the more extra-pair attraction women reported at high relative to
      low fertility (partial r = -.33, p(dir) = .03). In line with previous findings,
      we found support for the hypothesis that the degree to which a woman's romantic
      partner displays indicators of high-fitness genes affects women's attractions to
      their own partner and other men at high fertility.

PMID- 22984513
TI  - Fragments of HdhQ150 mutant huntingtin form a soluble oligomer pool that declines
      with aggregate deposition upon aging.
AB  - Cleavage of the full-length mutant huntingtin (mhtt) protein into smaller,
      soluble aggregation-prone mhtt fragments appears to be a key process in the
      neuropathophysiology of Huntington's Disease (HD). Recent quantification studies
      using TR-FRET-based immunoassays showed decreasing levels of soluble mhtt
      correlating with an increased load of aggregated mhtt in the aging HdhQ150 mouse
      brain. To better characterize the nature of these changes at the level of native
      mhtt species, we developed a detection method that combines size exclusion
      chromatography (SEC) and time-resolved fluorescence resonance energy transfer (TR
      FRET) that allowed us to resolve and define the formation, aggregation and
      temporal dynamics of native soluble mhtt species and insoluble aggregates in the
      brain of the HdhQ150 knock-in mouse. We found that mhtt fragments and not full
      length mhtt form oligomers in the brains of one month-old mice long before
      disease phenotypes and mhtt aggregate histopathology occur. As the HdhQ150 mice
      age, brain levels of soluble full-length mhtt protein remain similar. In
      contrast, the soluble oligomeric pool of mhtt fragments slightly increases during
      the first two months before it declines between 3 and 8 months of age. This
      decline inversely correlates with the formation of insoluble mhtt aggregates. We
      also found that the pool-size of soluble mhtt oligomers is similar in age-matched
      heterozygous and homozygous HdhQ150 mouse brains whereas insoluble aggregate
      formation is greatly accelerated in the homozygous mutant brain. The capacity of
      the soluble mhtt oligomer pool therefore seems exhausted already in the
      heterozygous state and likely kept constant by changes in flux and, as a
      consequence, increased rate of insoluble aggregate formation. We demonstrate that
      our novel findings in mice translate to human HD brain but not HD patient
      fibroblasts.

PMID- 22984514
TI  - Genome-wide identification and analysis of the TIFY gene family in grape.
AB  - BACKGROUND: The TIFY gene family constitutes a plant-specific group of genes with
      a broad range of functions. This family encodes four subfamilies of proteins,
      including ZML, TIFY, PPD and JASMONATE ZIM-Domain (JAZ) proteins. JAZ proteins
      are targets of the SCF(COI1) complex, and function as negative regulators in the
      JA signaling pathway. Recently, it has been reported in both Arabidopsis and rice
      that TIFY genes, and especially JAZ genes, may be involved in plant defense
      against insect feeding, wounding, pathogens and abiotic stresses. Nonetheless,
      knowledge concerning the specific expression patterns and evolutionary history of
      plant TIFY family members is limited, especially in a woody species such as
      grape. METHODOLOGY/PRINCIPAL FINDINGS: A total of two TIFY, four ZML, two PPD and
      11 JAZ genes were identified in the Vitis vinifera genome. Phylogenetic analysis
      of TIFY protein sequences from grape, Arabidopsis and rice indicated that the
      grape TIFY proteins are more closely related to those of Arabidopsis than those
      of rice. Both segmental and tandem duplication events have been major
      contributors to the expansion of the grape TIFY family. In addition, synteny
      analysis between grape and Arabidopsis demonstrated that homologues of several
      grape TIFY genes were found in the corresponding syntenic blocks of Arabidopsis,
      suggesting that these genes arose before the divergence of lineages that led to
      grape and Arabidopsis. Analyses of microarray and quantitative real-time RT-PCR
      expression data revealed that grape TIFY genes are not a major player in the
      defense against biotrophic pathogens or viruses. However, many of these genes
      were responsive to JA and ABA, but not SA or ET. CONCLUSION: The genome-wide
      identification, evolutionary and expression analyses of grape TIFY genes should
      facilitate further research of this gene family and provide new insights
      regarding their evolutionary history and regulatory control.

PMID- 22984515
TI  - Deficiency of the promyelocytic leukemia protein fosters hepatitis C-associated
      hepatocarcinogenesis in mice.
AB  - Overwhelming lines of epidemiological evidence have indicated that persistent
      infection with hepatitis C virus (HCV) is a major risk for the development of
      hepatocellular carcinoma (HCC). We have recently shown that HCV core protein
      mediates functional inactivation of the promyelocytic leukemia (PML) tumor
      suppressor pathway. However, the role of PML in HCC development yet remains
      unclear. To clarify the function of PML in liver carcinogenesis and HCV
      associated pathogenesis we crossed PML-deficient mice with HCV transgene (HCV-Tg)
      expressing mice and treated the resulting animals with DEN/Phenobarbital, an
      established protocol for liver carcinogenesis. Seven months after treatment,
      livers were examined macroscopically and histologically. Genetic depletion of the
      tumor suppressor PML coincided with an increase in hepatocyte proliferation,
      resulting in development of multiple dysplastic nodules in 100% of the PML
      deficient livers and of HCCs in 53%, establishing a tumor suppressive function of
      PML in the liver. In animals expressing the HCV-transgene in PML-deficient
      background, HCC development occurred even in 73%, while only 7% of their wildtype
      littermates developed HCC. The neoplastic nature of the tumors was confirmed by
      histology and expression of the HCC marker glutamine synthetase. Several pro- and
      antiapoptotic factors were tested for differential expression and liver
      carcinogenesis was associated with impaired expression of the proapoptotic
      molecule TRAIL in PML-deficient mice. In conclusion, this study provides first in
      vivo evidence that the tumor suppressor PML acts as an important barrier in liver
      carcinogenesis and HCV-dependent liver pathology.

PMID- 22984516
TI  - Discrete model of opinion changes using knowledge and emotions as control
      variables.
AB  - We present a new model of opinion changes dependent on the agents emotional state
      and their information about the issue in question. Our goal is to construct a
      simple, yet nontrivial and flexible representation of individual attitude
      dynamics for agent based simulations, that could be used in a variety of social
      environments. The model is a discrete version of the cusp catastrophe model of
      opinion dynamics in which information is treated as the normal factor while
      emotional arousal (agitation level determining agent receptiveness and
      rationality) is treated as the splitting factor. Both variables determine the
      resulting agent opinion, which itself can be in favor of the studied position,
      against it, or neutral. Thanks to the flexibility of implementing communication
      between the agents, the model is potentially applicable in a wide range of
      situations. As an example of the model application, we study the dynamics of a
      set of agents communicating among themselves via messages. In the example, we
      chose the simplest, fully connected communication topology, to focus on the
      effects of the individual opinion dynamics, and to look for stable final
      distributions of agents with different emotions, information and opinions. Even
      for such simplified system, the model shows complex behavior, including phase
      transitions due to symmetry breaking by external propaganda.

PMID- 22984506
TI  - Effects of genetic variants previously associated with fasting glucose and
      insulin in the Diabetes Prevention Program.
AB  - Common genetic variants have been recently associated with fasting glucose and
      insulin levels in white populations. Whether these associations replicate in pre
      diabetes is not known. We extended these findings to the Diabetes Prevention
      Program, a clinical trial in which participants at high risk for diabetes were
      randomized to placebo, lifestyle modification or metformin for diabetes
      prevention. We genotyped previously reported polymorphisms (or their proxies)
      in/near G6PC2, MTNR1B, GCK, DGKB, GCKR, ADCY5, MADD, CRY2, ADRA2A, FADS1, PROX1,
      SLC2A2, GLIS3, C2CD4B, IGF1, and IRS1 in 3,548 Diabetes Prevention Program
      participants. We analyzed variants for association with baseline glycemic traits,
      incident diabetes and their interaction with response to metformin or lifestyle
      intervention. We replicated associations with fasting glucose at MTNR1B
      (P<0.001), G6PC2 (P = 0.002) and GCKR (P = 0.001). We noted impaired beta-cell
      function in carriers of glucose-raising alleles at MTNR1B (P<0.001), and an
      increase in the insulinogenic index for the glucose-raising allele at G6PC2
      (P<0.001). The association of MTNR1B with fasting glucose and impaired beta-cell
      function persisted at 1 year despite adjustment for the baseline trait,
      indicating a sustained deleterious effect at this locus. We also replicated the
      association of MADD with fasting proinsulin levels (P<0.001). We detected no
      significant impact of these variants on diabetes incidence or interaction with
      preventive interventions. The association of several polymorphisms with
      quantitative glycemic traits is replicated in a cohort of high-risk persons.
      These variants do not have a detectable impact on diabetes incidence or response
      to metformin or lifestyle modification in the Diabetes Prevention Program.

PMID- 22984517
TI  - Gene duplicability-connectivity-complexity across organisms and a neutral
      evolutionary explanation.
AB  - Gene duplication has long been acknowledged by biologists as a major evolutionary
      force shaping genomic architectures and characteristics across the Tree of Life.
      Major research has been conducting on elucidating the fate of duplicated genes in
      a variety of organisms, as well as factors that affect a gene's duplicability-
      that is, the tendency of certain genes to retain more duplicates than others. In
      particular, two studies have looked at the correlation between gene duplicability
      and its degree in a protein-protein interaction network in yeast, mouse, and
      human, and another has looked at the correlation between gene duplicability and
      its complexity (length, number of domains, etc.) in yeast. In this paper, we
      extend these studies to six species, and two trends emerge. There is an increase
      in the duplicability-connectivity correlation that agrees with the increase in
      the genome size as well as the phylogenetic relationship of the species. Further,
      the duplicability-complexity correlation seems to be constant across the species.
      We argue that the observed correlations can be explained by neutral evolutionary
      forces acting on the genomic regions containing the genes. For the duplicability
      connectivity correlation, we show through simulations that an increasing trend
      can be obtained by adjusting parameters to approximate genomic characteristics of
      the respective species. Our results call for more research into factors, adaptive
      and non-adaptive alike, that determine a gene's duplicability.

PMID- 22984518
TI  - Negative feedback enables fast and flexible collective decision-making in ants.
AB  - Positive feedback plays a major role in the emergence of many collective animal
      behaviours. In many ants pheromone trails recruit and direct nestmate foragers to
      food sources. The strong positive feedback caused by trail pheromones allows fast
      collective responses but can compromise flexibility. Previous laboratory
      experiments have shown that when the environment changes, colonies are often
      unable to reallocate their foragers to a more rewarding food source. Here we show
      both experimentally, using colonies of Lasius niger, and with an agent-based
      simulation model, that negative feedback caused by crowding at feeding sites
      allows ant colonies to maintain foraging flexibility even with strong recruitment
      to food sources. In a constant environment, negative feedback prevents the
      frequently found bias towards one feeder (symmetry breaking) and leads to equal
      distribution of foragers. In a changing environment, negative feedback allows a
      colony to quickly reallocate the majority of its foragers to a superior food
      patch that becomes available when foraging at an inferior patch is already well
      underway. The model confirms these experimental findings and shows that the
      ability of colonies to switch to a superior food source does not require the
      decay of trail pheromones. Our results help to resolve inconsistencies between
      collective foraging patterns seen in laboratory studies and observations in the
      wild, and show that the simultaneous action of negative and positive feedback is
      important for efficient foraging in mass-recruiting insect colonies.

PMID- 22984519
TI  - Sentinel surveillance of influenza-like illness in two hospitals in Maracay,
      Venezuela: 2006-2010.
AB  - BACKGROUND: Limited information exists on the epidemiology of acute febrile
      respiratory illnesses in tropical South American countries such as Venezuela. The
      objective of the present study was to examine the epidemiology of influenza-like
      illness (ILI) in two hospitals in Maracay, Venezuela. METHODOLOGY/PRINCIPAL
      FINDINGS: We performed a prospective surveillance study of persons with ILI who
      presented for care at two hospitals in Maracay, Venezuela, from October 2006 to
      December 2010. A respiratory specimen and clinical information were obtained from
      each participant. Viral isolation and identification with immunofluorescent
      antibodies and molecular methods were employed to detect respiratory viruses such
      as adenovirus, influenza A and B, parainfluenza, and respiratory sincytial virus,
      among others. There were 916 participants in the study (median age: 17 years;
      range: 1 month--86 years). Viruses were identified in 143 (15.6%) subjects, and
      one participant was found to have a co-infection with more than one virus.
      Influenza viruses, including pandemic H1N1 2009, were the most frequently
      detected pathogens, accounting for 67.4% (97/144) of the viruses detected.
      Adenovirus (15/144), parainfluenza virus (13/144), and respiratory syncytial
      virus (11/144) were also important causes of ILI in this study. Pandemic H1N1
      2009 virus became the most commonly isolated influenza virus during its initial
      appearance in 2009. Two waves of the pandemic were observed: the first which
      peaked in August 2009 and the second--higher than the preceding - that peaked in
      October 2009. In 2010, influenza A/H3N2 re-emerged as the most predominant
      respiratory virus detected. CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the
      most commonly detected viral organisms among patients with acute febrile
      respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Pandemic
      H1N1 2009 influenza virus did not completely replace other circulating influenza
      viruses during its initial appearance in 2009. Seasonal influenza A/H3N2 was the
      most common influenza virus in the post-pandemic phase.

PMID- 22984520
TI  - Alveolar-membrane diffusing capacity limits performance in Boston marathon
      qualifiers.
AB  - PURPOSE: (1) to examine the relation between pulmonary diffusing capacity and
      marathon finishing time, and (2), to evaluate the accuracy of pulmonary diffusing
      capacity for nitric oxide (DLNO) in predicting marathon finishing time relative
      to that of pulmonary diffusing capacity for carbon monoxide (DLCO). METHODS: 28
      runners [18 males, age = 37 (SD 9) years, body mass = 70 (13) kg, height = 173
      (9) cm, percent body fat = 17 (7) %] completed a test battery consisting of
      measurement of DLNO and DLCO at rest, and a graded exercise test to determine
      running economy and aerobic capacity prior to the 2011 Steamtown Marathon
      (Scranton, PA). One to three weeks later, all runners completed the marathon
      (range: 2:22:38 to 4:48:55). Linear regressions determined the relation between
      finishing time and a variety of anthropometric characteristics, resting lung
      function variables, and exercise parameters. RESULTS: In runners meeting Boston
      Marathon qualification standards, 74% of the variance in marathon finishing time
      was accounted for by differences in DLNO relative to body surface area (BSA) (SEE
      = 11.8 min, p<0.01); however, the relation between DLNO or DLCO to finishing time
      was non-significant in the non-qualifiers (p = 0.14 to 0.46). Whereas both DLCO
      and DLNO were predictive of finishing time for all finishers, DLNO showed a
      stronger relation (r(2) = 0.30, SEE = 33.4 min, p<0.01) compared to DLCO when
      considering BSA. CONCLUSION: DLNO is a performance-limiting factor in only Boston
      qualifiers. This suggests that alveolar-capillary membrane conductance is a
      limitation to performance in faster marathoners. Additionally, DLNO/BSA predicts
      marathon finishing time and aerobic capacity more accurately than DLCO.

PMID- 22984521
TI  - Health assessment and seroepidemiologic survey of potential pathogens in wild
      Antillean manatees (Trichechus manatus manatus).
AB  - The Antillean manatee (Trichechus manatus manatus), a subspecies of the West
      Indian manatee, inhabits fresh, brackish, and warm coastal waters distributed
      along the eastern border of Central America, the northern coast of South America,
      and throughout the Wider Caribbean Region. Threatened primarily by human
      encroachment, poaching, and habitat degradation, Antillean manatees are listed as
      endangered by the International Union for the Conservation of Nature. The impact
      of disease on population viability remains unknown in spite of concerns
      surrounding the species' ability to rebound from a population crash should an
      epizootic occur. To gain insight on the baseline health of this subspecies, a
      total of 191 blood samples were collected opportunistically from wild Antillean
      manatees in Belize between 1997 and 2009. Hematologic and biochemical reference
      intervals were established, and antibody prevalence to eight pathogens with
      zoonotic potential was determined. Age was found to be a significant factor of
      variation in mean blood values, whereas sex, capture site, and season contributed
      less to overall differences in parameter values. Negative antibody titers were
      reported for all pathogens surveyed except for Leptospira bratislava, L.
      canicola, and L. icterohemorrhagiae, Toxoplasma gondii, and morbillivirus. As
      part of comprehensive health assessment in manatees from Belize, this study will
      serve as a benchmark aiding in early disease detection and in the discernment of
      important epidemiologic patterns in the manatees of this region. Additionally, it
      will provide some of the initial tools to explore the broader application of
      manatees as sentinel species of nearshore ecosystem health.

PMID- 22984522
TI  - Marine N-3 polyunsaturated fatty acids are inversely associated with risk of type
      2 diabetes in Asians: a systematic review and meta-analysis.
AB  - BACKGROUND: Prospective cohort studies in relation to the associations between n
      3 polyunsaturated fatty acids (PUFA) and risk of type 2 diabetes (T2D) were
      inconsistent. Differences in tissue n-3 PUFA compositions in subjects with and
      without T2D were also inconsistent in both cohort and case-control studies. We
      conducted a systematic review and meta-analysis of prospective cohort studies to
      examine the associations of fish and n-3 PUFA intake with T2D risk. The
      differences in tissue n-3 PUFA compositions in subjects with and without T2D were
      investigated based on cohort and case-control studies. METHODS AND FINDINGS:
      PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI)
      and Chinese VIP database up to January 2012 was used to identify relevant
      studies, and reference lists from retrieved studies were reviewed. Two authors
      independently extracted the data. Random-effects models were used to pool the
      summary relative risk (RR). Twenty-four studies including 24,509 T2D patients and
      545,275 participants were identified. For cohort studies, the summary RR of T2D
      for the highest vs lowest categories of total fish, marine n-3 PUFA and alpha
      linolenic acid intake was 1.07 (95% CI: 0.91, 1.25), 1.07 (95% CI: 0.95, 1.20)
      and 0.93 (95% CI: 0.81, 1.07), respectively. Subgroup analyses indicated that
      summary RR (highest vs lowest category) of T2D for fish and marine n-3 PUFA
      intake was 0.89 (95% CI: 0.81, 0.98) and 0.87 (95% CI: 0.79, 0.96) for Asian
      populations, and 1.20 (95% CI: 1.01, 1.44) and 1.16 (95% CI: 1.04, 1.28) for
      Western populations. Asian subjects with T2D had significantly lower tissue
      compositions of C22:6n-3 (SMD: -1.43; 95% CI: -1.75, -1.12) and total n-3 PUFA
      (SMD: -1.41; 95% CI: -2.23, -0.59) compared with those without T2D. CONCLUSION:
      This systematic review and meta-analysis provides evidence that marine n-3 PUFA
      have beneficial effects on the prevention of T2D in Asian populations.

PMID- 22984523
TI  - Novel small noncoding RNAs in mouse spermatozoa, zygotes and early embryos.
AB  - The recent discovery of a significant amount of RNA in spermatozoa contradicted
      the previously held belief that paternal contribution was limited to one copy of
      the genome. Furthermore, detection of RNA in sperm raised the intriguing question
      of its possible role in embryonic development. The possibility that RNAs may
      serve as epigenetic determinants was supported by experiments showing inheritance
      of epigenetic traits in mice mediated by RNA. We used high-throughput, large
      scale sequencing technology to analyze sperm RNA. The RNA sequences generated
      were diverse in terms of length and included mRNAs, rRNAs, piRNAs, and miRNAs. We
      studied two small noncoding RNAs enriched in mature sperm, designated sperm RNAs
      (spR) -12 and -13. They are both encoded in a piRNA locus on chromosome 17, but
      neither their length (20-21 nt), nor their sequences correspond to known piRNAs
      or miRNAs. They are resistant to periodate-oxidation-mediated reaction, implying
      that they undergo terminal post-transcriptional modification. Both were detected
      in sperm and ovulated unfertilized oocytes, present in one-cell embryos and
      maintained in preimplantation stages, but not at later differentiation stages.
      These findings offer a new perspective regarding a possibly important role for
      gamete-specific small RNAs in early embryogenesis.

PMID- 22984524
TI  - Effect of mass supplementation with ready-to-use supplementary food during an
      anticipated nutritional emergency.
AB  - BACKGROUND: Previous studies have shown the benefits of ready-to-use
      supplementary food (RUSF) distribution in reducing the incidence and prevalence
      of severe acute malnutrition. METHODS AND FINDINGS: To compare the incidence of
      wasting, stunting and mortality between children aged 6 to 23 mo participating
      and not participating in distributions of RUSF, we implemented two exhaustive
      prospective cohorts including all children 60 cm to 80 cm, resident in villages
      of two districts of Maradi region in Niger (n = 2238). Villages (20) were
      selected to be representative of the population. All registered children were
      eligible for the monthly distributions between July and October 2010. Age, sex,
      height, weight, and Mid-Upper Arm Circumference (MUAC) were measured at baseline
      and two weeks after each distribution; the amount and type of distribution and
      the amount shared and remaining were also assessed. We compared the incidence of
      wasting, stunting, and mortality among children participating in the distribution
      (intervention) of RUSF versus children not participating in the distribution
      (comparison).The absolute rate of wasting was 1.59 events per child-year (503
      events/315.3 child-year) in the intervention group and 1.78 events per child-year
      (322 events/180.4 child-year) in the comparison group [corrected].The
      intervention group had a small but higher weight-for-length Z-score gain (-0.2 z
      vs. -0.3 z) and less loss of MUAC than the comparison group (-2.8 vs. -4.0 mm).
      There was no difference in length gain (2.7 vs. 2.8 cm). Mortality was lower for
      children whose households received the intervention than those who did not
      (adjusted HR 0.55, 95% CI: 0.32-0.98). CONCLUSIONS: Short-term distribution with
      RUSF for children 6 to 23 months improve the nutritional status of children at
      risk for malnutrition. Fewer children who participated in the RUSF distribution
      died than those who did not.

PMID- 22984525
TI  - Bleeding risk during treatment of acute thrombotic events with subcutaneous LMWH
      compared to intravenous unfractionated heparin; a systematic review.
AB  - BACKGROUND: Low Molecular Weight Heparins (LMWH) are at least as effective
      antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still
      unclear whether the safety profiles of LMWH and UFH differ. We performed a
      systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH
      and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute
      coronary syndromes (ACS). Major bleeding was the primary end point. METHODS:
      Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up
      to May 2010 with no language restrictions. Randomized controlled trials in which
      subcutaneous LMWH were compared to intravenous UFH for the treatment of acute
      thrombotic events were selected. Two reviewers independently screened studies and
      extracted data on study design, study quality, incidence of major bleeding,
      patients' characteristics, type, dose and number of daily administrations of
      LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios
      (OR) and 95% confidence intervals (CI) were calculated using the random effects
      model. RESULTS: Twenty-seven studies were included. A total of 14,002 patients
      received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding
      was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60-1.04). In
      patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47-1.00).
      CONCLUSION: The results of our systematic review suggest that the use of LMWH in
      the treatment of VTE might be associated with a reduction in major bleeding
      compared with UFH. The choice of which heparin to use to minimize bleeding risk
      must be based on the single patient, taking into account the bleeding profile of
      different heparins in different settings.

PMID- 22984526
TI  - Nix protein positively regulates NF-kappaB activation in gliomas.
AB  - Previous reports indicate that the NIX/BNIP3L gene acts as a pro-apoptotic factor
      by interacting with BCL2 and BCL-XL, playing an important role in hypoxia
      dependent cell death and acting as a tumor suppressor. However, many studies also
      showed that NIX is linked to a protective role and cell survival in cancer cells.
      Nuclear factor-kappaB (NF-kappaB) can attenuate apoptosis in human cancers in
      response to chemotherapeutic agents and ionizing radiation. We observed an
      absence of i-kappaBalpha (NF-kappaB activation inhibitor) expression, but a
      greater expression of Nix and p-NF-kappaB proteins in the Nix-wt U251 cells,
      which was not observed in the Nix-kn cells under hypoxic conditions. Using
      electrophoretic mobility shift assay (EMSA) and luciferase detection, the
      activation of NF-kappaB was detected only in the Nix-wt U251 cells with hypoxia.
      These data imply that Nix protein might play a role in the positive regulation of
      the NF-kappaB pathway. Moreover, 46 cases of glioma also showed high levels of
      Nix protein expression, which was always accompanied by high p-NF-kappaB
      expression. Patients with Nix (+) showed less tissue apoptosis behavior in
      glioblastoma (GBM), unlike that observed in the Nix-negative patients (-). The
      same apoptotic tendency was also identified in anaplastic astrocytoma (AA)
      groups, but not in astrocytoma (AS). On analyzing the Kaplan-Meier curve, better
      tumor-free survival was observed only in cases of astrocytoma, and not in AA and
      GBM. Thus, our study indicates that Nix protein might have multiple functions in
      regulating glioma behaviors. In the low-grade gliomas (astrocytoma) with low
      expression of NF-kappaB, the cell death-inducing function that occurs through a
      Bax mechanism might predominate and act as a tumor suppressor. While in the
      malignant gliomas (AA and GBM), with higher expression of the NIX gene and with
      activity of the NF-kappaB pathway, the oncogene function of Nix was predominant.

PMID- 22984527
TI  - Anti-Mullerian hormone serum values and ovarian reserve: can it predict a
      decrease in fertility after ovarian stimulation by ART cycles?
AB  - BACKGROUND: A variety of indicators of potentially successful ovarian stimulation
      cycles are available, including biomarkers such as anti-Mullerian hormone. The
      aim of our study was to confirm the usefulness of serum anti-Mullerian hormone
      assay in predicting ovarian response and reproductive outcome in women eligible
      for ART cycles. MATERIALS: Forty-six women undergoing ART cycles at the Centre
      for Reproductive Medicine in Parma were recruited from March-to-June 2010.
      INCLUSION CRITERIA: age<42 years; body-mass-index = 20-25; regular menstrual
      cycles; basal serum FSH concentration <12 IU/L and basal serum estradiol
      concentration <70 pg/mL. The couples included in our study reported a variety of
      primary infertility causes. All women underwent FSH stimulation and pituitary
      suppression (GnRH-agonist/GnRH-antagonist protocols). Women were considered poor
      responders if they had <= 3 oocytes; normal-responders 4-9 oocytes and high
      responders >= 10 oocytes. Serum samples for the AMH assays were obtained on the
      first and last days of stimulation. A P value <= 0.05 was considered
      statistically significant. RESULT: FSH levels increased significantly when AMH
      levels decreased. The total dose of r-FSH administered to induce ovulation was
      not correlated to AMH. The number of follicles on the hCG, serum estradiol levels
      on the hCG-day, and the number of retrieved oocytes were significantly correlated
      to AMH. The number of fertilized oocytes was significantly correlated to the AMH
      levels. No significant correlation was found between obtained embryos or
      transferred embryos and AMH. Basal serum AMH levels were significantly higher
      than those measured on the hCG-day, which appeared significantly reduced. There
      was a significant correlation between AMH in normal responders and AMH in both
      high and poor responders. CONCLUSIONS: Our data confirm the clinical usefulness
      of AMH in ART-cycles to customize treatment protocols and suggest the necessity
      of verifying an eventual permanent decrease in AMH levels after IVF.

PMID- 22984528
TI  - Susceptibility towards enterotoxigenic Escherichia coli F4ac diarrhea is governed
      by the MUC13 gene in pigs.
AB  - Enterotoxigenic Escherichia coli (ETEC) F4ac is a major determinant of diarrhea
      and mortality in neonatal and young pigs. Susceptibility to ETEC F4ac is governed
      by the intestinal receptor specific for the bacterium and is inherited as a
      monogenic dominant trait. To identify the receptor gene (F4acR), we first mapped
      the locus to a 7.8-cM region on pig chromosome 13 using a genome scan with 194
      microsatellite markers. A further scan with high density markers on chromosome 13
      refined the locus to a 5.7-cM interval. Recombination breakpoint analysis defined
      the locus within a 2.3-Mb region. Further genome-wide mapping using 39,720
      informative SNPs revealed that the most significant markers were proximal to the
      MUC13 gene in the 2.3-Mb region. Association studies in a collection of diverse
      outbred populations strongly supported that MUC13 is the most likely responsible
      gene. We characterized the porcine MUC13 gene that encodes two transcripts:
      MUC13A and MUC13B. Both transcripts have the characteristic PTS regions of mucins
      that are enriched in distinct tandem repeats. MUC13B is predicated to be heavily
      O-glycosylated, forming the binding site of the bacterium; while MUC13A does not
      have the O-glycosylation binding site. Concordantly, 127 independent pigs
      homozygous for MUC13A across diverse breeds are all resistant to ETEC F4ac, and
      all 718 susceptible animals from the broad breed panel carry at least one MUC13B
      allele. Altogether, we conclude that susceptibility towards ETEC F4ac is governed
      by the MUC13 gene in pigs. The finding has an immediate translation into breeding
      practice, as it allows us to establish an efficient and accurate diagnostic test
      for selecting against susceptible animals. Moreover, the finding improves our
      understanding of mucins that play crucial roles in defense against enteric
      pathogens. It revealed, for the first time, the direct interaction between MUC13
      and enteric bacteria, which is poorly understood in mammals.

PMID- 22984529
TI  - Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide
      population-based cohort study.
AB  - OBJECTIVE: In a nationwide, population-based cohort study we assessed the risk of
      diabetes mellitus (DM) in HIV-infected individuals compared with the general
      population, and evaluated the impact of risk factors for DM in HIV-infected
      individuals. METHODS: We identified 4,984 Danish-born HIV-infected individuals
      from the Danish HIV Cohort Study and a Danish born population-based age- and
      gender-matched comparison cohort of 19,936 individuals (study period: 1996-2009).
      Data on DM was obtained from the Danish National Hospital Registry and the Danish
      National Prescription Registry. Incidence rate ratios (IRR) and impact of risk
      factors including exposure to Highly Active Antiretroviral Therapy (HAART) and
      antiretroviral drugs were estimated by Poisson regression analyses. RESULTS: In
      the period 1996-1999 risk of DM was higher in HIV-infected individuals compared
      to the comparison cohort (adjusted IRR: 2.83; 95%CI: 1.57-5.09), both before
      (adjusted IRR: 2.40; 95%CI: 1.03-5.62) and after HAART initiation (adjusted IRR:
      3.24; 95% CI: 1.42-7.39). In the period 1999-2010 the risk of DM in HIV-infected
      individuals did not differ from that of the comparison cohort (adjusted IRR:
      0.90; 95% CI: 0.72-1.13), although the risk was decreased before HAART-initiation
      (adjusted IRR: 0.45; 95%CI: 0.21-0.96). Increasing age, BMI and the presence of
      lipoatrophy increased the risk of DM, as did exposure to indinavir, saquinavir,
      stavudine and didanosine. CONCLUSION: Native HIV-infected individuals do not have
      an increased risk of developing DM compared to a native background population
      after year 1998. Some antiretroviral drugs, not used in modern antiretroviral
      treatment, seem to increase the risk of DM.

PMID- 22984530
TI  - Diversity of Acinetobacter baumannii in four French military hospitals, as
      assessed by multiple locus variable number of tandem repeats analysis.
AB  - BACKGROUND: Infections by A. calcoaceticus-A. baumannii (ACB) complex isolates
      represent a serious threat for wounded and burn patients. Three international
      multidrug-resistant (MDR) clones (EU clone I-III) are responsible for a large
      proportion of nosocomial infections with A. baumannii but other emerging strains
      with high epidemic potential also occur. METHODOLOGY/PRINCIPAL FINDINGS: We
      automatized a Multiple locus variable number of tandem repeats (VNTR) analysis
      (MLVA) protocol and used it to investigate the genetic diversity of 136 ACB
      isolates from four military hospitals and one childrens hospital. Acinetobacter
      sp other than baumannii isolates represented 22.6% (31/137) with a majority being
      A. pittii. The genotyping protocol designed for A.baumannii was also efficient to
      cluster A. pittii isolates. Fifty-five percent of A. baumannii isolates belonged
      to the two international clones I and II, and we identified new clones which
      members were found in the different hospitals. Analysis of two CRISPR-cas systems
      helped define two clonal complexes and provided phylogenetic information to help
      trace back their emergence. CONCLUSIONS/SIGNIFICANCE: The increasing occurrence
      of A. baumannii infections in the hospital calls for measures to rapidly
      characterize the isolates and identify emerging clones. The automatized MLVA
      protocol can be the instrument for such surveys. In addition, the investigation
      of CRISPR/cas systems may give important keys to understand the evolution of some
      highly successful clonal complexes.

PMID- 22984531
TI  - Fasting enhances the response of glioma to chemo- and radiotherapy.
AB  - BACKGROUND: Glioma, including anaplastic astrocytoma and glioblastoma multiforme
      (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is
      a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median
      survival. The treatment of GBM is multimodal and includes surgical resection,
      followed by adjuvant radio-and chemotherapy. We have previously reported that
      short-term starvation (STS) enhances the therapeutic index of chemo-treatments by
      differentially protecting normal cells against and/or sensitizing tumor cells to
      chemotoxicity. METHODOLOGY AND PRINCIPAL FINDINGS: To test the effect of
      starvation on glioma cells in vitro, we treated primary mouse glia, murine GL26,
      rat C6 and human U251, LN229 and A172 glioma cells with Temozolomide in ad lib
      and STS mimicking conditions. In vivo, mice with subcutaneous or intracranial
      models of GL26 glioma were starved for 48 hours prior to radio- or chemotherapy
      and the effects on tumor progression and survival were measured. Starvation
      mimicking conditions sensitized murine, rat and human glioma cells, but not
      primary mixed glia, to chemotherapy. In vivo, starvation for 48 hours, which
      causes a significant reduction in blood glucose and circulating insulin-like
      growth factor 1 (IGF-1) levels, sensitized both subcutaneous and intracranial
      glioma models to radio-and chemotherapy. CONCLUSION: Starvation-induced cancer
      sensitization to radio- or chemotherapy leads to extended survival in the in vivo
      glioma models tested. These results indicate that fasting and fasting-mimicking
      interventions could enhance the efficacy of existing cancer treatments against
      aggressive glioma in patients.

PMID- 22984532
TI  - Neutrophils are not less sensitive than other blood leukocytes to the genomic
      effects of glucocorticoids.
AB  - BACKGROUND: Neutrophils are generally considered less responsive to
      glucocorticoids compared to other inflammatory cells. The reported increase in
      human neutrophil survival mediated by these drugs partly supports this assertion.
      However, it was recently shown that dexamethasone exerts potent anti-inflammatory
      effects in equine peripheral blood neutrophils. Few comparative studies of
      glucocorticoid effects in neutrophils and other leukocytes have been reported and
      a relative insensitivity of neutrophils to these drugs could not be ruled out.
      OBJECTIVE: We assessed glucocorticoid-responsiveness in equine and human
      peripheral blood neutrophils and neutrophil-depleted leukocytes. METHODS: Blood
      neutrophils and neutrophil-depleted leukocytes were isolated from 6 healthy
      horses and 4 human healthy subjects. Cells were incubated for 5 h with or without
      LPS (100 ng/mL) alone or combined with hydrocortisone, prednisolone or
      dexamethasone (10(-8) M and 10(-6) M). IL-1beta, TNF-alpha, IL-8, glutamine
      synthetase and GR-alpha mRNA expression was quantified by qPCR. Equine
      neutrophils were also incubated for 20 h with or without the three
      glucocorticoids and cell survival was assessed by flow cytometry and light
      microscopy on cytospin preparations. RESULTS: We found that glucocorticoids down
      regulated LPS-induced pro-inflammatory mRNA expression in both cell populations
      and species. These drugs also significantly increased glutamine synthetase gene
      expression in both equine cell populations. The magnitude of glucocorticoid
      response between cell populations was generally similar in both species. We also
      showed that dexamethasone had a comparable inhibitory effect on pro-inflammatory
      gene expression in both human and equine neutrophils. As reported in other
      species, glucocorticoids significantly increase the survival in equine
      neutrophils. CONCLUSIONS: Glucocorticoids exert genomic effects of similar
      magnitude on neutrophils and on other blood leukocytes. We speculate that the
      poor response to glucocorticoids observed in some chronic neutrophilic diseases
      such as severe asthma or COPD is not explained by a relative lack of inhibition
      of these drugs on pro-inflammatory cytokines expression in neutrophils.

PMID- 22984533
TI  - Predicting human preferences using the block structure of complex social
      networks.
AB  - With ever-increasing available data, predicting individuals' preferences and
      helping them locate the most relevant information has become a pressing need.
      Understanding and predicting preferences is also important from a fundamental
      point of view, as part of what has been called a "new" computational social
      science. Here, we propose a novel approach based on stochastic block models,
      which have been developed by sociologists as plausible models of complex networks
      of social interactions. Our model is in the spirit of predicting individuals'
      preferences based on the preferences of others but, rather than fitting a
      particular model, we rely on a Bayesian approach that samples over the ensemble
      of all possible models. We show that our approach is considerably more accurate
      than leading recommender algorithms, with major relative improvements between 38%
      and 99% over industry-level algorithms. Besides, our approach sheds light on
      decision-making processes by identifying groups of individuals that have
      consistently similar preferences, and enabling the analysis of the
      characteristics of those groups.

PMID- 22984534
TI  - Detection of Mycobacterium tuberculosis GlcB or HspX Antigens or devR DNA impacts
      the rapid diagnosis of tuberculous meningitis in children.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is the most common form of
      neurotuberculosis and the fifth most common form of extrapulmonary TB. Early
      diagnosis and prompt treatment are the cornerstones of effective disease
      management. The accurate diagnosis of TBM poses a challenge due to an extensive
      differential diagnosis, low bacterial load and paucity of cerebrospinal fluid
      (CSF) especially in children. METHODOLOGY/PRINCIPAL FINDINGS: We describe the
      utility of ELISA and qPCR for the detection of Mycobacterium tuberculosis (M. tb)
      proteins (GlcB, HspX, MPT51, Ag85B and PstS1) and DNA for the rapid diagnosis of
      TBM. CSF filtrates (n = 532) derived from children were classified as 'Definite'
      TBM (M. tb culture positive, n = 29), 'Probable and Possible' TBM (n = 165) and
      'Not-TBM' including other cases of meningitis or neurological disorders (n =
      338). ROC curves were generated from ELISA and qPCR data of 'Definite' TBM and
      Non-Tuberculous infectious meningitis (NTIM) samples and cut-off values were
      derived to provide >= 95% specificity. devR qPCR, GlcB, HspX and PstS1 ELISAs
      showed 100% (88;100) sensitivity and 96-97% specificity in 'Definite' TBM
      samples. The application of these cut-offs to 'Probable and Possible' TBM groups
      yielded excellent sensitivity (98%, 94;99) and specificity (98%, 96;99) for qPCR
      and for GlcB, HspX and MPT51 antigen ELISAs (sensitivity 92-95% and specificity
      93-96%). A test combination of qPCR with GlcB and HspX ELISAs accurately detected
      all TBM samples at a specificity of ~90%. Logistic regression analysis indicated
      that these tests significantly added value to the currently used algorithms for
      TBM diagnosis. CONCLUSIONS: The detection of M. tb GlcB/HspX antigens/devR DNA in
      CSF is likely to improve the utility of existing algorithms for TBM diagnosis and
      also hasten the speed of diagnosis.

PMID- 22984536
TI  - Nematode spatial and ecological patterns from tropical and temperate rainforests.
AB  - Large scale diversity patterns are well established for terrestrial macrobiota
      (e.g. plants and vertebrates), but not for microscopic organisms (e.g.
      nematodes). Due to small size, high abundance, and extensive dispersal,
      microbiota are assumed to exhibit cosmopolitan distributions with no
      biogeographical patterns. This assumption has been extrapolated from local
      spatial scale studies of a few taxonomic groups utilizing morphological
      approaches. Recent molecularly-based studies, however, suggest something quite
      opposite. Nematodes are the most abundant metazoans on earth, but their diversity
      patterns are largely unknown. We conducted a survey of nematode diversity within
      three vertical strata (soil, litter, and canopy) of rainforests at two
      contrasting latitudes in the North American meridian (temperate: the Olympic
      National Forest, WA, U.S.A and tropical: La Selva Biological Station, Costa Rica)
      using standardized sampling designs and sample processing protocols. To describe
      nematode diversity, we applied an ecometagenetic approach using 454
      pyrosequencing. We observed that: 1) nematode communities were unique without
      even a single common species between the two rainforests, 2) nematode communities
      were unique among habitats in both rainforests, 3) total species richness was
      300% more in the tropical than in the temperate rainforest, 4) 80% of the species
      in the temperate rainforest resided in the soil, whereas only 20% in the tropics,
      5) more than 90% of identified species were novel. Overall, our data provided no
      support for cosmopolitanism at both local (habitats) and large (rainforests)
      spatial scales. In addition, our data indicated that biogeographical patterns
      typical of macrobiota also exist for microbiota.

PMID- 22984535
TI  - Multi-scale biomechanical remodeling in aging and genetic mutant murine mitral
      valve leaflets: insights into Marfan syndrome.
AB  - Mitral valve degeneration is a key component of the pathophysiology of Marfan
      syndrome. The biomechanical consequences of aging and genetic mutation in mitral
      valves are poorly understood because of limited tools to study this in mouse
      models. Our aim was to determine the global biomechanical and local cell-matrix
      deformation relationships in the aging and Marfan related Fbn1 mutated murine
      mitral valve. To conduct this investigation, a novel stretching apparatus and
      gripping method was implemented to directly quantify both global tissue
      biomechanics and local cellular deformation and matrix fiber realignment in
      murine mitral valves. Excised mitral valve leaflets from wild-type and Fbn1
      mutant mice from 2 weeks to 10 months in age were tested in circumferential
      orientation under continuous laser optical imaging. Mouse mitral valves stiffen
      with age, correlating with increases in collagen fraction and matrix fiber
      alignment. Fbn1 mutation resulted in significantly more compliant valves (modulus
      1.34 +/- 0.12 vs. 2.51 +/- 0.31 MPa, respectively, P<.01) at 4 months,
      corresponding with an increase in proportion of GAGs and decrease in elastin
      fraction. Local cellular deformation and fiber alignment change linearly with
      global tissue stretch, and these slopes become more extreme with aging. In
      comparison, Fbn1 mutated valves have decoupled cellular deformation and fiber
      alignment with tissue stretch. Taken together, quantitative understanding of
      multi-scale murine planar tissue biomechanics is essential for establishing
      consequences of aging and genetic mutations. Decoupling of local cell-matrix
      deformation kinematics with global tissue stretch may be an important mechanism
      of normal and pathological biomechanical remodeling in valves.

PMID- 22984537
TI  - Co-crystalization and in vitro biological characterization of 5-aryl-4-(5
      substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors.
AB  - A potential therapeutic strategy for targeting cancer that has gained much
      interest is the inhibition of the ATP binding and ATPase activity of the
      molecular chaperone Hsp90. We have determined the structure of the human
      Hsp90alpha N-terminal domain in complex with a series of 5-aryl-4-(5-substituted
      2-4-dihydroxyphenyl)-1,2,3-thiadiazoles. The structures provide the molecular
      details for the activity of these inhibitors. One of these inhibitors, ICPD 34,
      causes a structural change that affects a mobile loop, which adopts a
      conformation similar to that seen in complexes with ADP, rather than the
      conformation generally seen with the pyrazole/isoxazole-resorcinol class of
      inhibitors. Competitive binding to the Hsp90 N-terminal domain was observed in a
      biochemical assay, and these compounds showed antiproliferative activity and
      induced apoptosis in the HCT116 human colon cancer cell line. These inhibitors
      also caused induction of the heat shock response with the upregulation of Hsp72
      and Hsp27 protein expression and the depletion of Hsp90 clients, CRAF, ERBB2 and
      CDK4, thus confirming that antiproliferative activity was through the inhibition
      of Hsp90. The presence of increased levels of the cleavage product of PARP
      indicated apoptosis in response to Hsp90 inhibitors. This work provides a
      framework for the further optimization of thiadiazole inhibitors of Hsp90.
      Importantly, we demonstrate that the thiadiazole inhibitors display a more
      limited core set of interactions relative to the clinical trial candidate NVP
      AUY922, and consequently may be less susceptible to resistance derived through
      mutations in Hsp90.

PMID- 22984539
TI  - Extreme reproduction and survival of a true cliffhanger: the endangered Plant
      Borderea chouardii (Dioscoreaceae).
AB  - Cliff sides are extreme habitats, often sheltering a rich and unique flora. One
      example is the dioecious herb Borderea chouardii (Dioscoreaceae), which is a
      Tertiary, tropical relict, occurring only on two adjacent vertical cliffs in the
      world. We studied its reproductive biology, which in some aspects is extreme,
      especially the unusual double mutualistic role of ants as both pollinators and
      dispersers. We made a 2-year pollination census and four years of seed-dispersal
      experiments, recording flower visitors and dispersal rates. Fruit and seed set,
      self-sowing of seeds, seedling recruitment, and fate of seedlings from seeds
      sowed by different agents were scored over a period of 17 years. The ants Lasius
      grandis and L. cinereus were the main pollinators, whereas another ant Pheidole
      pallidula dispersed seeds. Thus ants functioned as double mutualists. Two thirds
      of all new seedlings came from self-sown seeds, and 1/3 was dispersed by ants,
      which gathered the seeds with their oil-rich elaiosome. Gravity played a minor
      role to dispersal. Both ant dispersal and self-sowing resulted in the same
      survival rate of seedlings. A double mutualism is a risky reproductive strategy,
      but B. chouardii buffers that by an unusual long-term demographic stability (some
      individuals exceed 300 years in lifespan) and its presence in a climatically very
      stable habitat, inaccessible to large herbivores. Such a combination of traits
      and habitat properties may explain the persistence of this relict species.

PMID- 22984538
TI  - Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a
      mouse experimental colitis model, independent of the anti-inflammatory effect.
AB  - BACKGROUND: Curcuma has long been used as an anti-inflammatory agent in
      inflammatory bowel disease. Since gastrointestinal motility is impaired in
      inflammatory states, the aim of this work was to evaluate if Curcuma Longa had
      any effect on intestinal motility. METHODS: The biological activity of Curcuma
      extract was evaluated against Carbachol induced contraction in isolated mice
      intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran
      Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma
      extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days
      respectively. Spontaneous contractions and the response to Carbachol and Atropine
      of ileum and colon were studied after colitis induction and Curcuma
      administration. RESULTS: Curcuma extract reduced the spontaneous contractions in
      the ileum and colon; the maximal response to Carbachol was inhibited in a non
      competitive and reversible manner. Similar results were obtained in ileum and
      colon from Curcuma fed mice. DSS administration decreased the motility, mainly in
      the colon and Curcuma almost restored both the spontaneous contractions and the
      response to Carbachol after 14 days assumption, compared to standard diet, but a
      prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced
      contractions. CONCLUSIONS: Curcuma extract has a direct and indirect myorelaxant
      effect on mouse ileum and colon, independent of the anti-inflammatory effect. The
      indirect effect is reversible and non-competitive with the cholinergic agent.
      These results suggest the use of curcuma extract as a spasmolytic agent.

PMID- 22984540
TI  - Phylogenetic analysis reveals common antimicrobial resistant Campylobacter coli
      population in antimicrobial-free (ABF) and commercial swine systems.
AB  - The objective of this study was to compare the population biology of
      antimicrobial resistant (AR) Campylobacter coli isolated from swine reared in the
      conventional and antimicrobial-free (ABF) swine production systems at farm,
      slaughter and environment. A total of 200 C. coli isolates selected from fecal,
      environmental, and carcass samples of ABF (n = 100) and conventional (n = 100)
      swine production systems were typed by multilocus sequence typing (MLST).
      Sequence data from seven housekeeping genes was analyzed for the identification
      of allelic profiles, sequence types (STs) and clonal complex determination.
      Phylogenetic trees were generated to establish the relationships between the
      genotyped isolates. A total of 51 STs were detected including two novel alleles
      (glnA 424 and glyA 464) and 14 novel STs reported for the first time. The
      majority of the C. coli isolates belonged to ST-854 (ABF: 31, conventional: 17),
      and were grouped in clonal complex ST-828 (ABF: 68%, conventional: 66%). The mean
      genetic diversity (H) for the ABF (0.3963+/-0.0806) and conventional (0.4655+/
      0.0714) systems were similar. The index of association (I(A)(S)) for the ABF
      (I(A)(S)= 0.1513) and conventional (I(A)(S) = 0.0991) C. coli populations were
      close to linkage equilibrium, indicative of a freely recombining population.
      Identical STs were detected between the pigs and their environment both at farm
      and slaughter. A minimum spanning tree revealed the close clustering of C. coli
      STs that originated from swine and carcass with those from the environment. In
      conclusion, our study reveals a genotypic diverse C. coli population that shares
      a common ancestry in the conventional and ABF swine production systems. This
      could potentially explain the high prevalence of antimicrobial resistant C. coli
      in the ABF system in the absence of antimicrobial selection pressure.

PMID- 22984541
TI  - Genomic characterization of DArT markers based on high-density linkage analysis
      and physical mapping to the Eucalyptus genome.
AB  - Diversity Arrays Technology (DArT) provides a robust, high throughput, cost
      effective method to query thousands of sequence polymorphisms in a single assay.
      Despite the extensive use of this genotyping platform for numerous plant species,
      little is known regarding the sequence attributes and genome-wide distribution of
      DArT markers. We investigated the genomic properties of the 7,680 DArT marker
      probes of a Eucalyptus array, by sequencing them, constructing a high density
      linkage map and carrying out detailed physical mapping analyses to the Eucalyptus
      grandis reference genome. A consensus linkage map with 2,274 DArT markers
      anchored to 210 microsatellites and a framework map, with improved support for
      ordering, displayed extensive collinearity with the genome sequence. Only 1.4 Mbp
      of the 75 Mbp of still unplaced scaffold sequence was captured by 45 linkage
      mapped but physically unaligned markers to the 11 main Eucalyptus
      pseudochromosomes, providing compelling evidence for the quality and completeness
      of the current Eucalyptus genome assembly. A highly significant correspondence
      was found between the locations of DArT markers and predicted gene models, while
      most of the 89 DArT probes unaligned to the genome correspond to sequences likely
      absent in E. grandis, consistent with the pan-genomic feature of this multi
      Eucalyptus species DArT array. These comprehensive linkage-to-physical mapping
      analyses provide novel data regarding the genomic attributes of DArT markers in
      plant genomes in general and for Eucalyptus in particular. DArT markers
      preferentially target the gene space and display a largely homogeneous
      distribution across the genome, thereby providing superb coverage for mapping and
      genome-wide applications in breeding and diversity studies. Data reported on
      these ubiquitous properties of DArT markers will be particularly valuable to
      researchers working on less-studied crop species who already count on DArT
      genotyping arrays but for which no reference genome is yet available to allow
      such detailed characterization.

PMID- 22984542
TI  - Direct chromatin PCR (DC-PCR): hypotonic conditions allow differentiation of
      chromatin states during thermal cycling.
AB  - Current methods to study chromatin configuration are not well suited for high
      throughput drug screening since they require large cell numbers and multiple
      experimental steps that include centrifugation for isolation of nuclei or DNA.
      Here we show that site specific chromatin analysis can be achieved in one step by
      simply performing direct chromatin PCR (DC-PCR) on cells. The basic underlying
      observation was that standard hypotonic PCR buffers prevent global cellular
      chromatin solubilization during thermal cycling while more loosely organized
      chromatin can be amplified. Despite repeated heating to >90  degrees C, 41 of 61
      tested 5' sequences of silenced genes (CDKN2A, PU.1, IRF4, FOSB, CD34) were not
      amplifiable while 47 could be amplified from expressing cells. Two gene regions
      (IRF4, FOSB) even required pre-heating of cells in isotonic media to allow this
      differentiation; otherwise none of 19 assayed sequences yielded PCR products.
      Cells with baseline expression or epigenetic reactivation gave similar DC-PCR
      results. Silencing during differentiation of CD34 positive cord blood cells
      closed respective chromatin while treatment of myeloma cells with an IRF4
      transcriptional inhibitor opened a site to DC-PCR that was occupied by RNA
      polymerase II and NFkappaB as determined by ChIP. Translation into real-time PCR
      can not be achieved with commercial real-time PCR buffers which potently open
      chromatin, but even with simple ethidium bromide addition to standard PCR
      mastermix we were able to identify hits in small molecules screens that
      suppressed IRF4 expression or reactivated CDKN2A in myeloma cells using
      densitometry or visual inspection of PCR plates under UV light. While need in
      drug development inspired this work, application to genome-wide analysis appears
      feasible using phi29 for selective amplification of open cellular chromatin
      followed by library construction from supernatants since such supernatants
      yielded similar results as gene specific DC-PCR.

PMID- 22984544
TI  - Increasing awareness about antibiotic use and resistance: a hands-on project for
      high school students.
AB  - BACKGROUND: Health-promoting education is essential to foster an informed society
      able to make decisions about socio-scientific issues based on scientifically
      sustained criteria. Antibiotic resistance is currently a major public health
      issue. Considering that irrational antibiotic use has been associated with the
      development and widespread of antibiotic resistant bacteria, educational
      interventions to promote prudent antibiotic consumption are required.
      METHODOLOGY/PRINCIPAL FINDINGS: This study focuses on the outcomes of an
      interventional program implemented at the University of Porto, Portugal, to
      promote awareness about antibiotic resistance at high school levels (15-17 year
      old). The project Microbiology recipes: antibiotics a la carte articulates a set
      of wet and dry lab activities designed to promote the participants' understanding
      of concepts and processes underlying antibiotics' production and activity, such
      as the notion of mechanisms of action of antibiotics. Following a mix-method
      approach based on a pre-/post design, the effectiveness of this project was
      assessed by gathering data from surveys, direct observation and analysis of
      artifacts of 42 high school students (aged 15 and 16 years). The results indicate
      that the participants developed a more comprehensive picture of antibiotic
      resistance. The project was shown to promote more sophisticated
      conceptualizations of bacteria and antibiotics, increased awareness about the
      perils of antibiotic resistance, and enhanced consciousness towards measures that
      can be undertaken to mitigate the problem. The participants regarded their
      experiences as enjoyable and useful, and believed that the project contributed to
      improve their understanding and raise their interest about the issues discussed.
      Furthermore, there were also improvements in their procedural skills concerning
      the laboratory techniques performed. CONCLUSIONS/SIGNIFICANCE: This study
      evidences the possibility of increasing high school students' awareness about the
      consequences of antibiotic resistance and the importance of judicious antibiotic
      use. The findings inform about the educational benefits of incorporating hands-on
      activities in science education programs.

PMID- 22984543
TI  - A novel stress-induced sugarcane gene confers tolerance to drought, salt and
      oxidative stress in transgenic tobacco plants.
AB  - BACKGROUND: Drought is a major abiotic stress that affects crop productivity
      worldwide. Sugarcane can withstand periods of water scarcity during the final
      stage of culm maturation, during which sucrose accumulation occurs. Meanwhile,
      prolonged periods of drought can cause severe plant losses. METHODOLOGY/PRINCIPAL
      FINDINGS: In a previous study, we evaluated the transcriptome of drought-stressed
      plants to better understand sugarcane responses to drought. Among the up
      regulated genes was Scdr1 (sugarcane drought-responsive 1). The aim of the
      research reported here was to characterize this gene. Scdr1 encodes a putative
      protein containing 248 amino acids with a large number of proline (19%) and
      cysteine (13%) residues. Phylogenetic analysis showed that ScDR1is in a clade
      with homologs from other monocotyledonous plants, separate from those of
      dicotyledonous plants. The expression of Scdr1 in different varieties of
      sugarcane plants has not shown a clear association with drought tolerance.
      CONCLUSIONS/SIGNIFICANCE: The overexpression of Scdr1 in transgenic tobacco
      plants increased their tolerance to drought, salinity and oxidative stress, as
      demonstrated by increased photosynthesis, water content, biomass, germination
      rate, chlorophyll content and reduced accumulation of ROS. Physiological
      parameters, such as transpiration rate (E), net photosynthesis (A), stomatal
      conductance (gs) and internal leaf CO(2) concentration, were less affected by
      abiotic stresses in transgenic Scdr1 plants compared with wild-type plants.
      Overall, our results indicated that Scdr1 conferred tolerance to multiple abiotic
      stresses, highlighting the potential of this gene for biotechnological
      applications.

PMID- 22984545
TI  - SiRNA inhibits replication of Langat virus, a member of the tick-borne
      encephalitis virus complex in organotypic rat brain slices.
AB  - Tick-borne encephalitis virus is the causative agent of tick-borne encephalitis,
      a potentially fatal neurological infection. Tick-borne encephalitis virus belongs
      to the family of flaviviruses and is transmitted by infected ticks. Despite the
      availability of vaccines, approximately 2000-3000 cases of tick-borne
      encephalitis occur annually in Europe for which no curative therapy is available.
      The antiviral effects of RNA mediated interference by small interfering RNA
      (siRNA) was evaluated in cell culture and organotypic hippocampal cultures.
      Langat virus, a flavivirus highly related to Tick-borne encephalitis virus
      exhibits low pathogenicity for humans but retains neurovirulence for rodents.
      Langat virus was used for the establishment of an in vitro model of tick-borne
      encephalitis. We analyzed the efficacy of 19 siRNA sequences targeting different
      regions of the Langat genome to inhibit virus replication in the two in vitro
      systems. The most efficient suppression of virus replication was achieved by
      siRNA sequences targeting structural genes and the 3' untranslated region. When
      siRNA was administered to HeLa cells before the infection with Langat virus, a
      96.5% reduction of viral RNA and more than 98% reduction of infectious virus
      particles was observed on day 6 post infection, while treatment after infection
      decreased the viral replication by more than 98%. In organotypic hippocampal
      cultures the replication of Langat virus was reduced by 99.7% by siRNA sequence
      D3. Organotypic hippocampal cultures represent a suitable in vitro model to
      investigate neuronal infection mechanisms and treatment strategies in a preserved
      three-dimensional tissue architecture. Our results demonstrate that siRNA is an
      efficient approach to limit Langat virus replication in vitro.

PMID- 22984546
TI  - The embryonic septum and ventral pallium, new sources of olfactory cortex cells.
AB  - The mammalian olfactory cortex is a complex structure located along the rostro
      caudal extension of the ventrolateral prosencephalon, which is divided into
      several anatomically and functionally distinct areas: the anterior olfactory
      nucleus, piriform cortex, olfactory tubercle, amygdaloid olfactory nuclei, and
      the more caudal entorhinal cortex. Multiple forebrain progenitor domains
      contribute to the cellular diversity of the olfactory cortex, which is invaded
      simultaneously by cells originating in distinct germinal areas in the dorsal and
      ventral forebrain. Using a combination of dye labeling techniques, we identified
      two novel areas that contribute cells to the developing olfactory cortices, the
      septum and the ventral pallium, from which cells migrate along a radial and then
      a tangential path. We characterized these cell populations by comparing their
      expression of calretinin, calbindin, reelin and Tbr1 with that of other olfactory
      cell populations.

PMID- 22984547
TI  - Sickness presenteeism predicts suboptimal self-rated health and sickness absence:
      a nationally representative study of the Swedish working population.
AB  - BACKGROUND: Earlier studies have suggested that sickness presenteeism (SP) may be
      a risk factor for future health problems. The purpose of the present study was to
      test this in a nationally representative prospective study of Swedish workers.
      METHODS: Prospective cohort with a representative sample of the Swedish working
      population surveyed in 2008 and 2010. Odds ratios (OR) with 95% confidence
      intervals (CI) were calculated using logistic regression. RESULTS: Those who
      reported more than 7 days of SP had higher risk of suboptimal SRH compared to
      those who reported no SP (OR = 5.95; 95% CI 4.98-7.12), also after adjustment for
      confounders (OR = 1.64; 95% CI 1.30-2.06). Those who reported 1-7 days of SP also
      had an increased risk before and after adjustments. Inclusion of self-rated
      physical and psychological work capacity did not attenuate the associations,
      whereas of emotional exhaustion attenuated the ORs to non-significance for both
      outcomes, indicating that the health consequences associated with SP are largely
      related to mental health. CONCLUSION: The results strengthen earlier findings
      suggesting that SP can be a risk factor for future suboptimal general health and
      sickness absence, particularly through mental health problems. This indicates
      that asking about SP could yield important information for employers,
      occupational health practitioners and GPs, possibly leading to more timely
      intervention that could decrease the risk of future sickness absence and more
      serious health problems, especially in the mental domain. Further studies of the
      possible causal pathways between SP and future health development are also
      warranted, especially since going to work is often seen as desirable also for
      those with poor health.

PMID- 22984548
TI  - Brain transcriptional and epigenetic associations with autism.
AB  - BACKGROUND: Autism is a common neurodevelopmental syndrome. Numerous rare genetic
      etiologies are reported; most cases are idiopathic. METHODOLOGY/PRINCIPAL
      FINDINGS: To uncover important gene dysregulation in autism we analyzed carefully
      selected idiopathic autistic and control cerebellar and BA19 (occipital) brain
      tissues using high resolution whole genome gene expression and whole genome DNA
      methylation microarrays. No changes in DNA methylation were identified in
      autistic brain but gene expression abnormalities in two areas of metabolism were
      apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and
      of protein translation. We also found associations between specific behavioral
      domains of autism and specific brain gene expression modules related to
      myelin/myelination, inflammation/immune response and purinergic signaling.
      CONCLUSIONS/SIGNIFICANCE: This work highlights two largely unrecognized molecular
      pathophysiological themes in autism and suggests differing molecular bases for
      autism behavioral endophenotypes.

PMID- 22984549
TI  - Dynamic microRNA profiles of hepatic differentiated human umbilical cord lining
      derived mesenchymal stem cells.
AB  - Despite the extensive hepatic differentiation potential of human umbilical cord
      lining-derived mesenchymal stem cells (hUC-MSC), little is known about the
      molecular mechanisms of hUC-MSC differentiation. At the post-transcriptional
      level, microRNAs are key players in the control of cell fate determination during
      differentiation. In this study, we aimed to identify microRNAs involved in the
      hepatic differentiation of hUC-MSCs. After successfully isolating hUC- MSCs, we
      induced hepatocyte formation in vitro with growth factors. After 26 days of
      induction, hUC-MSCs could express hepatocyte-specific genes, synthesize urea and
      glycogen and uptake low-density lipoprotein. Cellular total RNA from hUC-MSCs and
      hepatic differentiated hUC-MSCs was collected at 7 time points, including 2 days,
      6 days, 10 days, 14 days, 22 days and 26 days, for microRNA microarray analysis.
      Dynamic microRNA profiles were identified that did not overlap or only partially
      overlapped with microRNAs reported to be involved in human liver development,
      hepatocyte regeneration or hepatic differentiation of liver-derived progenitor
      cells. A total of 61 microRNAs among 1205 human and 144 human viral microRNAs
      displayed consistent changes and were altered at least 2-fold between hUC-MSCs
      and hepatic differentiated hUC-MSCs. Among these microRNAs, 25 were over
      expressed; this over-expression occurred either gradually or increased sharply
      and was maintained at a high level. A total of 36 microRNAs were under-expressed,
      with an expression pattern similar to that of the over-expressed microRNAs. The
      expression of the altered expressed microRNAs was also confirmed by quantitative
      reverse-transcription polymerase chain reaction. We also found that microRNAs
      involved in hepatic differentiation were not enriched in hepatocyte or
      hepatocellular carcinoma cells and can potentially target liver-enriched
      transcription factors and genes. The elucidation of the microRNA profile during
      the hepatic differentiation of hUC-MSCs provides the basis for clarifying the
      role of microRNAs in hUC-MSC hepatic differentiation and specific microRNA
      selection for the conversion of hUC-MSCs to hepatocytes.

PMID- 22984550
TI  - Immune receptors involved in Streptococcus suis recognition by dendritic cells.
AB  - Streptococcus suis is an important swine pathogen and an emerging zoonotic agent
      of septicemia and meningitis. Knowledge on host immune responses towards S. suis,
      and strategies used by this pathogen for subversion of these responses is scarce.
      The objective of this study was to identify the immune receptors involved in S.
      suis recognition by dendritic cells (DCs). Production of cytokines and expression
      of co-stimulatory molecules by DCs were shown to strongly rely on MyD88-dependent
      signaling pathways, suggesting that DCs recognize S. suis and become activated
      mostly through Toll-like receptor (TLR) signaling. Supporting this fact, TLR2(-/
      ) DCs were severely impaired in the release of several cytokines and the surface
      expression of CD86 and MHC-II. The release of IL-12p70 and CXC10, and the
      expression of CD40 were found to depend on signaling by both TLR2 and TLR9. The
      release of IL-23 and CXCL1 were partially dependent on NOD2. Finally, despite the
      fact that MyD88 signaling was crucial for DC activation and maturation, MyD88
      dependent pathways were not implicated in S. suis internalization by DCs. This
      first study on receptors involved in DC activation by S. suis suggests a major
      involvement of MyD88 signaling pathways, mainly (but not exclusively) through
      TLR2. A multimodal recognition involving a combination of different receptors
      seems essential for DC effective response to S. suis.

PMID- 22984551
TI  - Sex differences in carbohydrate metabolism are linked to gene expression in
      Caenorhabditis elegans.
AB  - The male and the hermaphrodite forms of the nematode Caenorhabditis elegans (C.
      elegans) differ markedly in anatomy, nervous system and behavior at adulthood.
      Using the male mutants fog-2, him-5, and him-8, we compared body proportions and
      composition, and aspects of carbohydrate metabolism and gene expression between
      the C. elegans sexes in three adult stages. In all experiments, both sexes were
      grown on the same plate and separated using flow cytometry. The fat to fat-free
      mass ratio and the body volume-adjusted fat mass is similar between the sexes,
      although the body size is more than 50% smaller in adult males than in age
      matched hermaphrodites. The volume-adjusted total RNA content is approximately 2
      fold lower in males. Biochemical and NMR-based analyses reveal higher trehalose
      levels and much lower glucose levels in males than in hermaphrodites. The
      resulting trehalose-to-glucose ratio is 5.4-fold higher in males. These sex
      differences are reflected in gene expression data because the genes encoding key
      enzymes of the glycolysis and trehalose synthesis pathways are more highly
      expressed in males than in hermaphrodites. Notably, expression of the
      phosphofructokinase gene (C50F4.2) is 29-fold higher in males. Comparative
      analysis of gene expression data identifies 285 male-specific and 160
      hermaphrodite-specific genes. These include transcription factor and C-type
      lectin-encoding genes. More than 35% of all C-type lectin genes are more highly
      expressed in males. The expression of many C-type lectin genes differs by a
      factor of >100 between the sexes. In conclusion, we found sex differences in
      carbohydrate metabolism that are linked to gene expression and identified certain
      lectin genes that are differentially expressed by the C. elegans sexes.

PMID- 22984552
TI  - Osmostress induces autophosphorylation of Hog1 via a C-terminal regulatory region
      that is conserved in p38alpha.
AB  - Many protein kinases require phosphorylation at their activation loop for
      induction of catalysis. Mitogen-activated protein kinases (MAPKs) are activated
      by a unique mode of phosphorylation, on neighboring Tyrosine and Threonine
      residues. Whereas many kinases obtain their activation via autophosphorylation,
      MAPKs are usually phosphorylated by specific, dedicated, MAPK kinases (MAP2Ks).
      Here we show however, that the yeast MAPK Hog1, known to be activated by the
      MAP2K Pbs2, is activated in pbs2Delta cells via an autophosphorylation activity
      that is induced by osmotic pressure. We mapped a novel domain at the Hog1 C
      terminal region that inhibits this activity. Removal of this domain provides a
      Hog1 protein that is partially independent of MAP2K, namely, partially rescues
      osmostress sensitivity of pbs2Delta cells. We further mapped a short domain (7
      amino acid residues long) that is critical for induction of autophosphorylation.
      Its removal abolishes autophosphorylation, but maintains Pbs2-mediated
      phosphorylation. This 7 amino acids stretch is conserved in the human p38alpha.
      Similar to the case of Hog1, it's removal from p38alpha abolishes p38alpha's
      autophosphorylation capability, but maintains, although reduces, its activation
      by MKK6. This study joins a few recent reports to suggest that, like many protein
      kinases, MAPKs are also regulated via induced autoactivation.

PMID- 22984553
TI  - BRCA1/2 mutations appear embryo-lethal unless rescued by low (CGG n<26) FMR1 sub
      genotypes: explanation for the "BRCA paradox"?
AB  - BRCA1/2 mutations and recently described constitutional FMR1 genotypes have,
      independently, been associated with prematurely diminished ovarian reserve.
      Whether they interrelate in distribution, and whether observed effects of BRCA1/2
      and FMR1 on ovaries are independent of each other, is unknown. In a prospective
      comparative cohort study, we, therefore, investigated the distribution of
      constitutional FMR1 genotypes, normal (norm), heterozygous (het) and homozygous
      (hom), and of their respective sub-genotypes (high/low), in 99 BRCA1/2 mutation
      positive women and 410 female controls to determine whether distribution patterns
      differed between study and control patients. In contrast to controls, BRCA1/2
      carriers demonstrated almost complete absence of all constitutional FMR1
      genotypes except for sub-genotypes with low (CGG (n<26)) alleles. Cross
      tabulation between BRCA1/2-positive patients and controls confirmed significant
      group membership, related to FMR1 distribution (P<0.0001). These results offer as
      most likely explanation the conclusion that BRCA1/2 mutations are embryo-lethal,
      unless rescued by low (CGG (n<26)) FMR1 sub-genotypes, present in approximately
      one quarter of all women. Women with low FMR1 sub-genotypes, therefore, should
      reflect increased BRCA1/2-associated cancer risks, while the remaining
      approximately 75 percent should face almost no such risks. If confirmed, this
      observation offers opportunities for more efficient and less costly BRCA1/2
      cancer screening. The study also suggests that previously reported risk towards
      prematurely diminished ovarian reserve in association with BRCA mutations is FMR1
      mediated, and offers a possible explanation for the so-called "BRCA paradox" by
      raising the possibility that the widely perceived BRCA1/2-associated tumor risk
      is actually FMR1-mediated.

PMID- 22984555
TI  - Are patent medicine vendors effective agents in malaria control? Using lot
      quality assurance sampling to assess quality of practice in Jigawa, Nigeria.
AB  - BACKGROUND: Patent medicine vendors (PMV) provide antimalarial treatment and care
      throughout Sub-Saharan Africa, and can play an important role in the fight
      against malaria. Their close-to-client infrastructure could enable lifesaving
      artemisinin-based combination therapy (ACT) to reach patients in time. However,
      systematic assessments of drug sellers' performance quality are crucial if their
      role is to be managed within the health system. Lot quality assurance sampling
      (LQAS) could be an efficient method to monitor and evaluate PMV practice, but has
      so far never been used for this purpose. METHODS: In support of the Nigeria
      Malaria Booster Program we assessed PMV practices in three Senatorial Districts
      (SDs) of Jigawa, Nigeria. A two-stage LQAS assessed whether at least 80% of PMV
      stores in SDs used national treatment guidelines. Acceptable sampling errors were
      set in consultation with government officials (alpha and beta <0.10). The
      hypergeometric formula determined sample sizes and cut-off values for SDs. A
      structured assessment tool identified high and low performing SDs for quality of
      care indicators. FINDINGS: Drug vendors performed poorly in all SDs of Jigawa for
      all indicators. For example, all SDs failed for stocking and selling first-line
      antimalarials. PMV sold no longer recommended antimalarials, such as Chloroquine,
      Sulfadoxine-Pyrimethamine and oral Artesunate monotherapy. Most PMV were ignorant
      of and lacked training about new treatment guidelines that had endorsed ACTs as
      first-line treatment for uncomplicated malaria. CONCLUSION: There is urgent need
      to regularly monitor and improve the availability and quality of malaria
      treatment provided by medicine sellers in Nigeria; the irrational use of
      antimalarials in the ACT era revealed in this study bears a high risk of economic
      loss, death and development of drug resistance. LQAS has been shown to be a
      suitable method for monitoring malaria-related indicators among PMV, and should
      be applied in Nigeria and elsewhere to improve service delivery.

PMID- 22984554
TI  - Intense co-circulation of non-influenza respiratory viruses during the first wave
      of pandemic influenza pH1N1/2009: a cohort study in Reunion Island.
AB  - OBJECTIVE: The aim of the present study was to weigh up, at the community level,
      the respective roles played by pandemic Influenza (pH1N1) virus and co
      circulating human Non-Influenza Respiratory Viruses (NIRVs) during the first wave
      of the 2009 pH1N1 pandemic. METHODS: A population-based prospective cohort study
      was conducted in Reunion Island during the austral winter 2009 (weeks 30-44) that
      allowed identification of 125 households with at least one member who developed
      symptoms of Influenza-like illness (ILI). Three consecutive nasal swabs were
      collected from each household member (443 individuals) on day 0, 3 and 8 post-ILI
      report and tested for pH1N1 and 15 NIRVs by RT-PCR. RESULTS: Two successive waves
      of viral infections were identified: a first wave (W33-37) when pH1N1 was
      dominant and co-circulated with NIRVs, sharply interrupted by a second wave (W38
      44), almost exclusively composed of NIRVs, mainly human Rhinoviruses (hRV) and
      Coronaviruses (hCoV). Data suggest that some interference may occur between NIRVs
      and pH1N1 when they co-circulate within the same household, where NIRVs were more
      likely to infect pH1N1 negative individuals than pH1N1 positive peers (relative
      risk: 3.13, 95% CI: 1.80-5.46, P<0.001). Viral shedding was significantly shorter
      (P = 0.035) in patients who were co-infected by pH1N1 and NIRV or by two
      different NIRVs compared to those who were infected with only one virus, whatever
      this virus was (pH1N1 or NIRVs). Although intense co-circulation of NIRVs
      (especially hRV) likely brought pH1N1 under the detection threshold, it did not
      prevent spread of the pandemic Influenza virus within the susceptible population
      nor induction of an extensive herd immunity to it. CONCLUSION: Our results
      suggest that NIRV co-infections during Influenza epidemics may act as cofactors
      that contribute to shape an outbreak and modulate the attack rate. They further
      warrant broad spectrum studies to fully understand viral epidemics.

PMID- 22984556
TI  - Localization microscopy (SPDM) reveals clustered formations of P-glycoprotein in
      a human blood-brain barrier model.
AB  - P-glycoprotein (Pgp; also known as MDR1, ABCB1) is the most important and best
      studied efflux transporter at the blood-brain barrier (BBB); however, the
      organization of Pgp is unknown. The aim of this study was to employ the recently
      developed super-resolution fluorescence microscopy method spectral precision
      distance microscopy/spectral position determination microscopy (SPDM) to
      investigate the spatial distribution of Pgp in the luminal plasma membrane of
      brain capillary endothelial cells. Potential disturbing effects of cell membrane
      curvatures on the distribution analysis are addressed with computer simulations.
      Immortalized human cerebral microvascular endothelial cells (hCMEC/D3) served as
      a model of human BBB. hCMEC/D3 cells were transduced with a Pgp-green fluorescent
      protein (GFP) fusion protein incorporated in a lentivirus-derived vector. The
      expression and localization of the Pgp-GFP fusion protein was visualized by SPDM.
      The limited resolution of SPDM in the z-direction leads to a projection during
      the imaging process affecting the appeared spatial distribution of fluorescence
      molecules in the super-resolution images. Therefore, simulations of molecule
      distributions on differently curved cell membranes were performed and their
      projected spatial distribution was investigated. Function of the fusion protein
      was confirmed by FACS analysis after incubation of cells with the fluorescent
      probe eFluxx-ID Gold in absence and presence of verapamil. More than 112,000
      single Pgp-GFP molecules (corresponding to approximately 5,600 Pgp-GFP molecules
      per cell) were detected by SPDM with an averaged spatial resolution of
      approximately 40 nm in hCMEC/D3 cells. We found that Pgp-GFP is distributed in
      clustered formations in hCMEC/D3 cells while the influence of present random cell
      membrane curvatures can be excluded based on the simulation results. Individual
      formations are distributed randomly over the cell membrane.

PMID- 22984557
TI  - Reduction of soybean meal non-starch polysaccharides and alpha-galactosides by
      solid-state fermentation using cellulolytic bacteria obtained from different
      environments.
AB  - Soybean meal (SBM) is an important protein source in animal feed. However, the
      levels of SBM inclusion are restricted in some animal species by the presence of
      antinutritional factors (ANFs), including non-starch polysaccharides (NSPs) and
      alpha-galactosides (GOSs). The aim of this study was to reduce the soybean meal
      NSPs and GOSs by solid-state fermentation (SSF) using a combination of
      cellulolytic bacteria isolated from different environments (termites, earthworms,
      corn silage and bovine ruminal content). To analyse the key enzymatic activities,
      the isolates were grown in minimal media containing NSPs extracted from SBM. The
      selected bacterial strains belonged to the genera Streptomyces, Cohnella and
      Cellulosimicrobium. SSF resulted in a reduction of nearly 24% in the total NSPs,
      83% of stachyose and 69% of raffinose and an increase in the protein content.
      These results suggest that cellulolytic bacteria-based SSF processing facilitates
      SBM nutritional improvement. In addition, the use of fermented SBM in animal
      diets can be recommended.

PMID- 22984558
TI  - Distractor detection and suppression have a beneficial effect on attentional
      blink.
AB  - BACKGROUND: Attentional blink (AB) is a phenomenon that describes the difficulty
      individuals have in reporting the second of two masked targets if the second
      target (T2) arrives 200-500 ms after the first target (T1). Recent studies
      explain the AB from cognitive resources limitation to distractors interference.
      For example, the temporary loss of control (TLC) hypothesis suggests that the AB
      is conduced by distractors disrupting the input filter for target processing. The
      inhibition models suggest that the T1+1 distractor triggers a suppression
      mechanism which could be beneficial for T1 processing but would suppress T2 at
      short T1-T2 lags. These models consider that the AB is caused by the appearance
      of distractors. However, in the present study, two methods were taken to help
      individuals to detect the distractors more effectively. An attenuated AB deficit
      was found when the distractors could be excluded or suppressed in time. We
      consider that under an appropriate condition the distractors detection and
      suppression have a beneficial effect on attentional blink. METHODOLOGY/PRINCIPAL
      FINDINGS: Two methods were employed to help individuals to detect the distractors
      more effectively: enlarging the low-level-physical characteristic difference
      between targets and distractors (Experiment 1) and restricting the sets of
      distractors (Experiment 2). Attenuated AB deficits were found as using the above
      manipulations. CONCLUSIONS/SIGNIFICANCE: The present study found when the
      distractors are detected or identified quickly, they could be effectively
      suppressed, in order to reduce the interference from the targets and result in a
      smaller AB deficit. We suggest that the suppression mechanism for distractors
      have a beneficial effect on AB.

PMID- 22984559
TI  - Expression of VEGF receptors on endothelial cells in mouse skeletal muscle.
AB  - VEGFR surface localization plays a critical role in converting extracellular VEGF
      signaling towards angiogenic outcomes, and the quantitative characterization of
      these parameters is critical for advancing computational models; however the
      levels of these receptors on blood vessels is currently unknown. Therefore our
      aim is to quantitatively determine the VEGFR localization on endothelial cells
      from mouse hindlimb skeletal muscles. We contextualize this VEGFR quantification
      through comparison to VEGFR-levels on cells in vitro. Using quantitative
      fluorescence we measure and compare the levels of VEGFR1 and VEGFR2 on
      endothelial cells isolated from C57BL/6 and BALB/c gastrocnemius and tibialis
      anterior hindlimb muscles. Fluorescence measurements are calibrated using beads
      with known numbers of phycoerythrin molecules. The data show a 2-fold higher
      VEGFR1 surface localization relative to VEGFR2 with 2,000-3,700
      VEGFR1/endothelial cell and 1,300-2,000 VEGFR2/endothelial cell. We determine
      that endothelial cells from the highly glycolytic muscle, tibialis anterior,
      contain 30% higher number of VEGFR1 surface receptors than gastrocnemius; BALB/c
      mice display ~17% higher number of VEGFR1 than C57BL/6. When we compare these
      results to mouse fibroblasts in vitro, we observe high levels of VEGFR1
      (35,800/cell) and very low levels of VEGFR2 (700/cell), while in human
      endothelial cells in vitro, we observe that the balance of VEGFRs is inverted,
      with higher levels VEGFR2 (5,800/cell) and lower levels of VEGFR1 (1,800/cell).
      Our studies also reveal significant cell-to-cell heterogeneity in receptor
      expression, and the quantification of these dissimilarities ex vivo for the first
      time provides insight into the balance of anti-angiogenic or modulatory (VEGFR1)
      and pro-angiogenic (VEGFR2) signaling.

PMID- 22984560
TI  - Determinants and consequences of failure of linkage to antiretroviral therapy at
      primary care level in Blantyre, Malawi: a prospective cohort study.
AB  - BACKGROUND: Poor rates of linkage from HIV diagnosis to ART initiation are a
      major barrier to universal coverage of ART in sub-Saharan Africa, with reasons
      for failure poorly understood. In the first study of this kind at primary care
      level, we investigated the pathway to care in the Malawian National Programme,
      one of the strongest in Africa. METHODS AND FINDINGS: A prospective cohort study
      was undertaken at two primary care clinics in Blantyre, Malawi. Newly diagnosed
      HIV-positive adults (>15 years) were followed for 6-months to assess completion
      of eligibility assessments, initiation of ART and death. Two hundred and eighty
      participants were followed for 82.6 patient-years. ART eligibility assessments
      were problematic: only 134 (47.9%) received same day WHO staging and 121 (53.2%)
      completed assessments by 6-months. Completion of CD4 measurement (stage 1/2 only)
      was 81/153 (52.9%). By 6-months, 87/280 (31.1%) had initiated ART with higher
      uptake in participants who were ART eligible (68/91, 74.7%), and among
      participants who received same-day staging (52/134 [38.8%] vs. 35/146 [24.0%] p =
      0.007). Non-completion of ART eligibility assessments (adjusted hazard ratio:
      0.11, 95% CI: 0.06-0.21) was associated with failure to initiate ART. Retention
      in pre-ART care for non-ART initiators was low (55/193 [28.5%]). Of the 15 (5.4%)
      deaths, 11 (73.3%) occurred after ART initiation. CONCLUSIONS: Although uptake of
      ART was high and prompt for patients with known eligibility, there was frequent
      failure to complete eligibility assessment and poor retention in pre-ART care.
      HIV care programmes should urgently evaluate the way patients are linked to ART.
      In particular, there is a critical need for simplified, same-day ART eligibility
      assessments, reduced requirements for hospital visits, and active defaulter
      follow-up.

PMID- 22984561
TI  - Apoptosis induced by knockdown of uPAR and MMP-9 is mediated by inactivation of
      EGFR/STAT3 signaling in medulloblastoma.
AB  - BACKGROUND: Medulloblastoma is a highly invasive cancer of central nervous system
      diagnosed mainly in children. Matrix metalloproteinase-9 (MMP-9) and urokinase
      plasminogen activator receptor (uPAR) are over expressed in several cancers and
      well established for their roles in tumor progression. The present study is aimed
      to determine the consequences of targeting these molecules on medulloblastoma
      progression. METHODOLOGY/PRINCIPAL FINDINGS: Radiation is one of the foremost
      methods applied for treating cancer and considerable evidence showed that
      radiation elevated uPAR and MMP-9 expression in medulloblastoma cell. Therefore
      efforts are made to target these molecules in non-irradiated and irradiated
      medulloblastoma cells. Our results showed that siRNA-mediated knockdown of uPAR
      and MMP-9, either alone or in combination with radiation modulated a series of
      events leading to apoptosis. Down regulation of uPAR and MMP-9 inhibited the
      expression of anti-apoptotic molecules like Bcl-2, Bcl-xL, survivin, XIAP and
      cIAPI; activated BID cleavage, enhanced the expression of Bak and translocated
      cyctochrome C to cytosol. Capsase-3 and -9 activities were also increased in uPAR
      and MMP-9-downregulated cells. The apoptosis induced by targeting MMP-9 and uPAR
      was initiated by inhibiting epidermal growth factor receptor (EGFR) mediated
      activation of STAT3 and NF-kappaB related signaling molecules. Silencing uPAR and
      MMP-9 inhibited DNA binding activity of STAT3 and also reduced the recruitment of
      STAT3 protein at the promoter region of Bcl-2 and survivin genes. Our results
      suggest that inhibiting uPAR and MMP-9 reduced the expression of anti-apoptotic
      molecules by inactivating the transcriptional activity of STAT3. In addition,
      treating pre-established medulloblastoma with siRNAs against uPAR and MMP-9 both
      alone or in combination with radiation suppressed uPAR, MMP-9, EGFR, STAT3
      expression and induced Bak activation leading to apoptosis.
      CONCLUSION/SIGNIFICANCE: Taken together, our results illustrated that RNAi
      mediated targeting of uPAR and MMP-9 might have therapeutic potential against
      medulloblastoma.

PMID- 22984563
TI  - Investigating differences in vigilance tactic use within and between the sexes in
      eastern grey kangaroos.
AB  - Aggregation is thought to enhance an animal's security through effective predator
      detection and the dilution of risk. A decline in individual vigilance as group
      size increases is commonly reported in the literature and called the group size
      effect. However, to date, most of the research has only been directed toward
      examining whether this effect occurs at the population level. Few studies have
      explored the specific contributions of predator detection and risk dilution and
      the basis of individual differences in the use of vigilance tactics. We tested
      whether male and female (non-reproductive or with young) eastern grey kangaroos
      (Macropus giganteus) adopted different vigilance tactics when in mixed-sex groups
      and varied in their reliance on predator detection and/or risk dilution as group
      size changed. This species exhibits pronounced sexual dimorphism with females
      being much smaller than males, making them differentially vulnerable toward
      predators. We combined field observations with vigilance models describing the
      effects of detection and dilution on scanning rates as group size increased. We
      found that females with and without juveniles relied on predator detection and
      risk dilution, but the latter adjusted their vigilance to the proportion of
      females with juveniles within their group. Two models appeared to equally support
      the data for males suggesting that males, similarly to females, relied on
      predator detection and risk dilution but may also have adjusted their vigilance
      according to the proportion of mothers within their group. Differential
      vulnerability may cause sex differences in vigilance tactic use in this species.
      The presence of males within a group that do not, or only partially, contribute
      to predator detection and are less at risk may cause additional security costs to
      females. Our results call for reexamination of the classical view of the safety
      advantages of grouping to provide a more detailed functional interpretation of
      gregariousness.

PMID- 22984562
TI  - Mining gene expression signature for the detection of pre-malignant melanocytes
      and early melanomas with risk for metastasis.
AB  - BACKGROUND: Metastatic melanoma is a highly aggressive skin cancer and currently
      resistant to systemic therapy. Melanomas may involve genetic, epigenetic and
      metabolic abnormalities. Evidence is emerging that epigenetic changes might play
      a significant role in tumor cell plasticity and metastatic phenotype of melanoma
      cells. PRINCIPAL FINDINGS: In this study, we developed a systematic approach to
      identify genes implicated in melanoma progression. To do this, we used the
      Affymetrix GeneChip Arrays to screen 34,000 mouse transcripts in melan-a
      melanocytes, 4C pre-malignant melanocytes, 4C11- non-metastatic and 4C11+
      metastatic melanoma cell lines. The genome-wide association studies revealed
      pathways commonly over-represented in the transition from immortalized to pre
      malignant stage, and under-represented in the transition from non-metastatic to
      metastatic stage. Additionally, the treatment of cells with 10 uM 5-aza-2'
      deoxycytidine (5AzaCdR) for 48 hours allowed us to identify genes differentially
      re-expressed at specific stages of melan-a malignant transformation. Treatment of
      human primary melanocytes with the demethylating agent 5AzaCdR in combination to
      the histone deacetylase inhibitor Trichostatin A (TSA) revealed changes on
      melanocyte morphology and gene expression which could be an indicator of
      epigenetic flexibility in normal melanocytes. Moreover, changes on gene
      expression recognized by affecting the melanocyte biology (NDRG2 and VDR),
      phenotype of metastatic melanoma cells (HSPB1 and SERPINE1) and response to
      cancer therapy (CTCF, NSD1 and SRC) were found when Mel-2 and/or Mel-3-derived
      patient metastases were exposed to 5AzaCdR plus TSA treatment. Hierarchical
      clustering and network analyses in a panel of five patient-derived metastatic
      melanoma cells showed gene interactions that have never been described in
      melanomas. SIGNIFICANCE: Despite the heterogeneity observed in melanomas, this
      study demonstrates the utility of our murine melanoma progression model to
      identify molecular markers commonly perturbed in metastasis. Additionally, the
      novel gene expression signature identified here may be useful in the future into
      a model more closely related to translational research.

PMID- 22984564
TI  - Bidirectional activity of the NWC promoter is responsible for RAG-2 transcription
      in non-lymphoid cells.
AB  - The recombination-activating genes (RAG-1 and RAG-2) encode a V(D)J recombinase
      responsible for rearrangements of antigen-receptor genes during T and B cell
      development, and RAG expression is known to correlate strictly with the process
      of rearrangement. In contrast to RAG-1, the expression of RAG-2 was not
      previously detected during any other stage of lymphopoiesis or in any other
      normal tissue. Here we report that the CpG island-associated promoter of the NWC
      gene (the third evolutionarily conserved gene in the RAG locus), which is located
      in the second intron of RAG-2, has bidirectional activity and is responsible for
      the detectable transcription of RAG-2 in some non-lymphoid tissues. We also
      identify evolutionarily conserved promoter fragments responsible for this
      bidirectional activity, and show that it is activated by transcription factor
      ZFP143. The possible implications of our findings are briefly discussed.

PMID- 22984565
TI  - Structural evidence for a copper-bound carbonate intermediate in the peroxidase
      and dismutase activities of superoxide dismutase.
AB  - Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our
      understanding of oxidative damage. Its primary function is catalysing the
      dismutation of superoxide to O(2) and H(2)O(2). SOD also reacts with H(2)O(2),
      leading to the formation of a strong copper-bound oxidant species that can either
      inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate
      (or CO(2)) and H(2)O(2), this peroxidase activity is enhanced and produces the
      carbonate radical. This freely diffusible reactive oxygen species is proposed as
      the agent for oxidation of large substrates that are too bulky to enter the
      active site. Here, we provide direct structural evidence, from a 2.15 A
      resolution crystal structure, of (bi)carbonate captured at the active site of
      reduced SOD, consistent with the view that a bound carbonate intermediate could
      be formed, producing a diffusible carbonate radical upon reoxidation of copper.
      The bound carbonate blocks direct access of substrates to Cu(I), suggesting that
      an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide
      operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled
      electron transfer mechanism involving the bound carbonate rather than the
      solvent. Carbonate is captured in a different site when SOD is oxidised, being
      located in the active site channel adjacent to the catalytically important
      Arg143. This is the probable route of diffusion from the active site following
      reoxidation of the copper. In this position, the carbonate is poised for re-entry
      into the active site and binding to the reduced copper.

PMID- 22984566
TI  - Cooperative binding of transcription factors promotes bimodal gene expression
      response.
AB  - In the present work we extend and analyze the scope of our recently proposed
      stochastic model for transcriptional regulation, which considers an arbitrarily
      complex cis-regulatory system using only elementary reactions. Previously, we
      determined the role of cooperativity on the intrinsic fluctuations of gene
      expression for activating transcriptional switches, by means of master equation
      formalism and computer simulation. This model allowed us to distinguish between
      two cooperative binding mechanisms and, even though the mean expression levels
      were not affected differently by the acting mechanism, we showed that the
      associated fluctuations were different. In the present generalized model we
      include other regulatory functions in addition to those associated to an
      activator switch. Namely, we introduce repressive regulatory functions and two
      theoretical mechanisms that account for the biphasic response that some cis
      regulatory systems show to the transcription factor concentration. We have also
      extended our previous master equation formalism in order to include protein
      production by stochastic translation of mRNA. Furthermore, we examine the
      graded/binary scenarios in the context of the interaction energy between
      transcription factors. In this sense, this is the first report to show that the
      cooperative binding of transcription factors to DNA promotes the "all-or-none"
      phenomenon observed in eukaryotic systems. In addition, we confirm that gene
      expression fluctuation levels associated with one of two cooperative binding
      mechanism never exceed the fluctuation levels of the other.

PMID- 22984567
TI  - Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X
      syndrome reveals limited, call type specific deficits.
AB  - Fragile X syndrome (FXS) is a well-recognized form of inherited mental
      retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1)
      gene. The gene is located on the long arm of the X chromosome and encodes fragile
      X mental retardation protein (FMRP). Absence of FMRP in fragile X patients as
      well as in Fmr1 knockout (KO) mice results, among other changes, in abnormal
      dendritic spine formation and altered synaptic plasticity in the neocortex and
      hippocampus. Clinical features of FXS include cognitive impairment, anxiety,
      abnormal social interaction, mental retardation, motor coordination and speech
      articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs) when
      isolated from their mothers. Whether those social ultrasonic vocalizations are
      deficient in mouse models of FXS is unknown. Here we compared isolation-induced
      USVs generated by pups of Fmr1-KO mice with those of their wild type (WT)
      littermates. Though the total number of calls was not significantly different
      between genotypes, a detailed analysis of 10 different categories of calls
      revealed that loss of Fmr1 expression in mice causes limited and call-type
      specific deficits in ultrasonic vocalization: the carrier frequency of flat calls
      was higher, the percentage of downward calls was lower and that the frequency
      range of complex calls was wider in Fmr1-KO mice compared to their WT
      littermates.

PMID- 22984569
TI  - The amphibian chytrid fungus, Batrachochytrium dendrobatidis, in fully aquatic
      salamanders from Southeastern North America.
AB  - Little is known about the impact that the pathogenic amphibian chytrid fungus,
      Batrachochytrium dendrobatidis (Bd), has on fully aquatic salamander species of
      the eastern United States. As a first step in determining the impacts of Bd on
      these species, we aimed to determine the prevalence of Bd in wild populations of
      fully aquatic salamanders in the genera Amphiuma, Necturus, Pseudobranchus, and
      Siren. We sampled a total of 98 salamanders, representing nine species from sites
      in Florida, Mississippi, and Louisiana. Overall, infection prevalence was found
      to be 0.34, with significant differences among genera but no clear geographic
      pattern. We also found evidence for seasonal variation, but additional sampling
      throughout the year is needed to clarify this pattern. The high rate of infection
      discovered in this study is consistent with studies of other amphibians from the
      southeastern United States. Coupled with previously published data on life
      histories and population densities, the results presented here suggest that fully
      aquatic salamanders may be serving as important vectors of Bd and the interaction
      between these species and Bd warrants additional research.

PMID- 22984568
TI  - Peripheral blood gene expression as a novel genomic biomarker in complicated
      sarcoidosis.
AB  - Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung,
      typically spontaneously remits but in ~20% of cases progresses with severe lung
      dysfunction or cardiac and neurologic involvement (complicated sarcoidosis).
      Unfortunately, current biomarkers fail to distinguish patients with remitting
      (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to
      identify individuals at risk for complicated sarcoidosis. We utilized genome-wide
      peripheral blood gene expression analysis to identify a 20-gene sarcoidosis
      biomarker signature distinguishing sarcoidosis (n = 39) from healthy controls (n
      = 35, 86% classification accuracy) and which served as a molecular signature for
      complicated sarcoidosis (n = 17). As aberrancies in T cell receptor (TCR)
      signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR)
      signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature
      comprised of T cell signaling pathway genes associated with sarcoidosis
      (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved
      inferior in prediction accuracy in distinguishing complicated from uncomplicated
      sarcoidosis. Additional validation strategies included significant association of
      single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis
      susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG,
      RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1,
      IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this
      validated peripheral blood molecular gene signature appears to be a valuable
      biomarker in identifying cases with sarcoidoisis and predicting risk for
      complicated sarcoidosis.

PMID- 22984570
TI  - Immune complex signatures of patients with active and inactive SLE revealed by
      multiplex protein binding analysis on antigen microarrays.
AB  - Systemic lupus erythematosus is characterized by dysfunctional clearance of
      apoptotic debris and the development of pathogenic autoantibodies. While the
      complement system is also involved in the disease no attempt has been made to
      generate a comprehensive view of immune complex formation from various
      autoantigens. We increased the complexity of autoantibody profiles by measuring
      the binding of two complement proteins, C3 and C4, in addition to two antibody
      classes, IgG and IgM, to a collection of autoantigens. These complement
      components covalently bind to those microarray features where antibodies and
      other serum components induce complement activation. Using this technology, we
      compared functional serum antibody profiles of control subjects (n = 31) and
      patients with lupus erythematosus (n = 61) in the active (n = 22) and inactive (n
      = 39) phase of the disease. Multivariate analysis was applied to identify
      contributions of binding data on 25 antigens to the discrimination of the study
      groups. Receiver operating characteristic analysis was used to portray the
      discriminative property of each measured parameter for each antigen in pairwise
      group comparisons. Complement C3 and C4 deposition increased on autoantibody
      targets in spite of the decreased serum complement concentrations, and decreased
      on other autoantigens, demonstrating the imbalance of complement function in
      patients with lupus erythematosus. Our observations confirmed previously known
      markers of disease and showed that C3 and C4 deposition data were at least as
      powerful as Ig binding data in separating the study groups.

PMID- 22984571
TI  - The metabolic responses to aerial diffusion of essential oils.
AB  - Anxiety disorders are the most prevalent psychiatric disorders and affect a great
      number of people worldwide. Essential oils, take effects through inhalation or
      topical application, are believed to enhance physical, emotional, and spiritual
      well-being. Although clinical studies suggest that the use of essential oils may
      have therapeutic potential, evidence for the efficacy of essential oils in
      treating medical conditions remains poor, with a particular lack of studies
      employing rigorous analytical methods that capture its identifiable impact on
      human biology. Here, we report a comprehensive gas chromatography time-of-flight
      mass spectrometry (GC-TOFMS) based metabonomics study that reveals the aromas
      induced metabolic changes and the anxiolytic effect of aromas in elevated plus
      maze (EPM) induced anxiety model rats. The significant alteration of metabolites
      in the EPM group was attenuated by aromas treatment, concurrent with the
      behavioral improvement with significantly increased open arms time and open arms
      entries. Brain tissue and urinary metabonomic analysis identified a number of
      altered metabolites in response to aromas intervention. These metabolic changes
      included the increased carbohydrates and lowered levels of neurotransmitters
      (tryptophan, serine, glycine, aspartate, tyrosine, cysteine, phenylalanine,
      hypotaurine, histidine, and asparagine), amino acids, and fatty acids in the
      brain. Elevated aspartate, carbohydrates (sucrose, maltose, fructose, and
      glucose), nucleosides and organic acids such as lactate and pyruvate were also
      observed in the urine. The EPM induced metabolic differences observed in urine or
      brain tissue was significantly reduced after 10 days of aroma inhalation, as
      noted with the loss of statistical significance on many of the metabolites in the
      aroma-EPM group. This study demonstrates, for the first time, that the
      metabonomics approach can capture the subtle metabolic changes resulting from
      exposure to essential oils and provide the basis for pinpointing affected
      pathways in anxiety-related behavior, which will lead to an improved mechanistic
      understanding of anxiolytic effect of essential oils.

PMID- 22984572
TI  - Evaluation of remote delivery of Passive Integrated Transponder (PIT) technology
      to mark large mammals.
AB  - Methods to individually mark and identify free-ranging wildlife without trapping
      and handling would be useful for a variety of research and management purposes.
      The use of Passive Integrated Transponder technology could be an efficient method
      for collecting data for mark-recapture analysis and other strategies for
      assessing characteristics about populations of various wildlife species. Passive
      Integrated Transponder tags (PIT) have unique numbered frequencies and have been
      used to successfully mark and identify mammals. We tested for successful
      injection of PIT and subsequent functioning of PIT into gelatin blocks using 4
      variations of a prototype dart. We then selected the prototype dart that resulted
      in the least depth of penetration in the gelatin block to assess the ability of
      PIT to be successfully implanted into muscle tissue of white-tailed deer
      (Odocoileus virginianus) post-mortem and long-term in live, captive Rocky
      Mountain elk (Cervus elaphus). The prototype dart with a 12.7 mm (0.5 inch)
      needle length and no powder charge resulted in the shallowest mean (+/- SD)
      penetration depth into gelatin blocks of 27.0 mm (+/- 5.6 mm) with 2.0 psi
      setting on the Dan-Inject CO(2)-pressured rifle. Eighty percent of PIT were
      successfully injected in the muscle mass of white-tailed deer post-mortem with a
      mean (+/- SD) penetration depth of 22.2 mm (+/- 3.8 mm; n = 6). We injected PIT
      successfully into 13 live, captive elk by remote delivery at about 20 m that
      remained functional for 7 months. We successfully demonstrated that PIT could be
      remotely delivered in darts into muscle mass of large mammals and remain
      functional for >6 months. Although further research is warranted to fully develop
      the technique, remote delivery of PIT technology to large mammals is possible
      using prototype implant darts.

PMID- 22984573
TI  - Arabidopsis bHLH100 and bHLH101 control iron homeostasis via a FIT-independent
      pathway.
AB  - Iron deficiency induces a complex set of responses in plants, including
      developmental and physiological changes, to increase iron uptake from soil. In
      Arabidopsis, many transporters involved in the absorption and distribution of
      iron have been identified over the past decade. However, little is known about
      the signaling pathways and networks driving the various responses to low iron.
      Only the basic helix-loop-helix (bHLH) transcription factor FIT has been shown to
      control the expression of the root iron uptake machinery genes FRO2 and IRT1.
      Here, we characterize the biological role of two other iron-regulated
      transcription factors, bHLH100 and bHLH101, in iron homeostasis. First direct
      transcriptional targets of FIT were determined in vivo. We show that bHLH100 and
      bHLH101 do not regulate FIT target genes, suggesting that they play a non
      redundant role with the two closely related bHLH factors bHLH038 and bHLH039 that
      have been suggested to act in concert with FIT. bHLH100 and bHLH101 play a
      crucial role in iron-deficiency responses, as attested by their severe growth
      defects and iron homeostasis related phenotypes on low-iron media. To gain
      further insight into the biological role of bHLH100 and bHLH101, we performed
      microarray analysis using the corresponding double mutant and showed that bHLH100
      and bHLH101 likely regulate genes involved in the distribution of iron within the
      plant. Altogether, this work establishes bHLH100 and bHLH101 as key regulators of
      iron-deficiency responses independent of the master regulator FIT and sheds light
      on new regulatory networks important for proper growth and development under low
      iron conditions.

PMID- 22984574
TI  - The effect of tenofovir on vitamin D metabolism in HIV-infected adults is
      dependent on sex and ethnicity.
AB  - BACKGROUND: Tenofovir has been associated with renal phosphate wasting, reduced
      bone mineral density, and higher parathyroid hormone levels. The aim of this
      study was to carry out a detailed comparison of the effects of tenofovir versus
      non-tenofovir use on calcium, phosphate and, vitamin D, parathyroid hormone
      (PTH), and bone mineral density. METHODS: A cohort study of 56 HIV-1 infected
      adults at a single centre in the UK on stable antiretroviral regimes comparing
      biochemical and bone mineral density parameters between patients receiving either
      tenofovir or another nucleoside reverse transcriptase inhibitor. PRINCIPAL
      FINDINGS: In the unadjusted analysis, there was no significant difference between
      the two groups in PTH levels (tenofovir mean 5.9 pmol/L, 95% confidence intervals
      5.0 to 6.8, versus non-tenofovir; 5.9, 4.9 to 6.9; p = 0.98). Patients on
      tenofovir had significantly reduced urinary calcium excretion (median 3.01
      mmol/24 hours) compared to non-tenofovir users (4.56; p<0.0001). Stratification
      of the analysis by age and ethnicity revealed that non-white men but not women,
      on tenofovir had higher PTH levels than non-white men not on tenofovir (mean
      difference 3.1 pmol/L, 95% CI 5.3 to 0.9; p = 0.007). Those patients with optimal
      25-hydroxyvitamin D (>75 nmol/L) on tenofovir had higher 1,25-dihydroxyvitamin D
      [1,25(OH)(2)D] (median 48 pg/mL versus 31; p = 0.012), fractional excretion of
      phosphate (median 26.1%, versus 14.6; p = 0.025) and lower serum phosphate
      (median 0.79 mmol/L versus 1.02; p = 0.040) than those not taking tenofovir.
      CONCLUSIONS: The effects of tenofovir on PTH levels were modified by sex and
      ethnicity in this cohort. Vitamin D status also modified the effects of tenofovir
      on serum concentrations of 1,25(OH)(2)D and phosphate.

PMID- 22984575
TI  - Targeted DNA methylation using an artificially bisected M.HhaI fused to zinc
      fingers.
AB  - Little is known about the effects of single DNA methylation events on gene
      transcription. The ability to direct the methylation toward a single unique site
      within a genome would have broad use as a tool to study the effects of specific
      epigenetic changes on transcription. A targeted enzyme might also be useful in a
      therapy for diseases with an epigenetic component or as a means to site
      specifically label DNA. Previous studies have sought to target methyltransferase
      activity by fusing DNA binding proteins to methyltransferases. However, the
      methyltransferase domain remains active even when the DNA binding protein is
      unbound, resulting in significant off-target methylation. A better strategy would
      make methyltransferase activity contingent upon the DNA binding protein's
      association with its DNA binding site. We have designed targeted
      methyltransferases by fusing zinc fingers to the fragments of artificially
      bisected, assembly-compromised methyltransferases. The zinc fingers' binding
      sites flank the desired target site for methylation. Zinc finger binding
      localizes the two fragments near each other encouraging their assembly only over
      the desired site. Through a combination of molecular modeling and experimental
      optimization in E. coli, we created an engineered methyltransferase derived from
      M.HhaI with 50-60% methylation at a target site and nearly undetectable levels of
      methylation at a non-target M.HhaI site (1.4 +/- 2.4%). Using a restriction
      digestion assay, we demonstrate that localization of both fragments
      synergistically increases methylation at the target site, illustrating the
      promise of our approach.

PMID- 22984576
TI  - Disturbed relaxin signaling pathway and testicular dysfunction in mouse offspring
      upon maternal exposure to simazine.
AB  - Simazine is a triazine herbicide that is being widely applied worldwide and
      commonly detected in surface and groundwater. Despite its popular use in
      controlling weeds and algae, very limited information is available regarding its
      toxicity. In the present study, pregnant mice were orally exposed to low doses
      (0, 5, 50, or 500 ug/kg body weight per day) of simazine during gestation and
      lactation, during which no overt maternal toxic response was detected, and their
      offspring was assessed. Simazine-exposed male offspring showed decreased body,
      testicular, and epididymis weight, increased testicular apoptosis, and decreased
      sperm concentrations. Differentially-expressed genes in the testes of male
      offspring exposed to simazine were identified by DNA microarray, revealing 775
      upregulated and 791 downregulated genes; among these, the relaxin-family peptide
      receptor 1 (Rxfp1), which is the receptor for relaxin hormone, was significantly
      downregulated. In addition, the expression of target genes in the relaxin
      pathway, including nitric oxide synthase 2 (Nos2) and Nos3, was significantly
      decreased in simazine-exposed F1 testes. Moreover, simazine inhibited NO release,
      and knockdown of Rxfp1 blocked the inhibitory action of simazine on NO production
      in testicular Leydig cells. Therefore, the present study provides a better
      understanding of the toxicities associated with the widely used herbicide
      simazine at environmentally relevant doses by demonstrating that maternal
      exposure interferes with the pleotropic relaxin-NO signaling pathway, impairing
      normal development and reproductive activity of male offspring.

PMID- 22984577
TI  - NAD(P)H:quinone oxidoreductase 1 (NQO1) localizes to the mitotic spindle in human
      cells.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is an FAD containing quinone reductase
      that catalyzes the 2-electron reduction of a broad range of quinones. The 2
      electron reduction of quinones to hydroquinones by NQO1 is believed to be a
      detoxification process since this reaction bypasses the formation of the highly
      reactive semiquinone. NQO1 is expressed at high levels in normal epithelium,
      endothelium and adipocytes as well as in many human solid tumors. In addition to
      its function as a quinone reductase NQO1 has been shown to reduce superoxide and
      regulate the 20 S proteasomal degradation of proteins including p53. Biochemical
      studies have indicated that NQO1 is primarily located in the cytosol, however,
      lower levels of NQO1 have also been found in the nucleus. In these studies we
      demonstrate using immunocytochemistry and confocal imaging that NQO1 was found
      associated with mitotic spindles in cells undergoing division. The association of
      NQO1 with the mitotic spindles was observed in many different human cell lines
      including nontransformed cells (astrocytes, HUVEC) immortalized cell lines
      (HBMEC, 16HBE) and cancer (pancreatic adenocarcinoma, BXPC3). Confocal analysis
      of double-labeling experiments demonstrated co-localization of NQO1with alpha
      tubulin in mitotic spindles. In studies with BxPc-3 human pancreatic cancer cells
      the association of NQO1 with mitotic spindles appeared to be unchanged in the
      presence of NQO1 inhibitors ES936 or dicoumarol suggesting that NQO1 can
      associate with the mitotic spindle and still retain catalytic activity. Analysis
      of archival human squamous lung carcinoma tissue immunostained for NQO1
      demonstrated positive staining for NQO1 in the spindles of mitotic cells. The
      purpose of this study is to demonstrate for the first time the association of the
      quinone reductase NQO1 with the mitotic spindle in human cells.

PMID- 22984578
TI  - Effect of supervised students' involvement on diagnostic accuracy in hospitalized
      medical patients--a prospective controlled study.
AB  - BACKGROUND: During internships most medical students engage in history taking and
      physical examination during evaluation of hospitalized patients. However, the
      students' ability for pattern recognition is not as developed as in medical
      experts and complete history taking is often not repeated by an expert, so
      important clues may be missed. On the other hand, students' history taking is
      usually more extensive than experts' history taking and medical students discuss
      their findings with a Supervisor. Thus the effect of student involvement on
      diagnostic accuracy is unclear. We therefore compared the diagnostic accuracy for
      patients in the medical emergency department with and without student involvement
      in the evaluation process. METHODOLOGY/PRINCIPAL FINDINGS: Patients in the
      medical emergency department were assigned to evaluation by either a supervised
      medical student or an emergency department physician. We only included patients
      who were admitted to our hospital and subsequently cared for by another medical
      team on the ward. We compared the working diagnosis from the emergency department
      with the discharge diagnosis. A total of 310 patients included in the study were
      cared for by 41 medical students and 21 emergency department physicians. The
      working diagnosis was changed in 22% of the patients evaluated by physicians
      evaluation and in 10% of the patients evaluated by supervised medical students (p
      = .006). There was no difference in the expenditures for diagnostic procedures,
      length of stay in the emergency department or patient comorbidity complexity
      level. CONCLUSION/SIGNIFICANCE: Involvement of closely supervised medical
      students in the evaluation process of hospitalized medical patients leads to an
      improved diagnostic accuracy compared to evaluation by an emergency department
      physician alone.

PMID- 22984580
TI  - Systematic analysis of small RNAs associated with human mitochondria by deep
      sequencing: detailed analysis of mitochondrial associated miRNA.
AB  - Mitochondria are one of the central regulators of many cellular processes beyond
      its well established role in energy metabolism. The inter-organellar crosstalk is
      critical for the optimal function of mitochondria. Many nuclear encoded proteins
      and RNA are imported to mitochondria. The translocation of small RNA (sRNA)
      including miRNA to mitochondria and other sub-cellular organelle is still not
      clear. We characterized here sRNA including miRNA associated with human
      mitochondria by cellular fractionation and deep sequencing approach. Mitochondria
      were purified from HEK293 and HeLa cells for RNA isolation. The sRNA library was
      generated and sequenced using Illumina system. The analysis showed the presence
      of unique population of sRNA associated with mitochondria including miRNA.
      Putative novel miRNAs were characterized from unannotated sRNA sequences. The
      study showed the association of 428 known, 196 putative novel miRNAs to
      mitochondria of HEK293 and 327 known, 13 putative novel miRNAs to mitochondria of
      HeLa cells. The alignment of sRNA to mitochondrial genome was also studied. The
      targets were analyzed using DAVID to classify them in unique networks using GO
      and KEGG tools. Analysis of identified targets showed that miRNA associated with
      mitochondria regulates critical cellular processes like RNA turnover, apoptosis,
      cell cycle and nucleotide metabolism. The six miRNAs (counts >1000) associated
      with mitochondria of both HEK293 and HeLa were validated by RT-qPCR. To our
      knowledge, this is the first systematic study demonstrating the associations of
      sRNA including miRNA with mitochondria that may regulate site-specific turnover
      of target mRNA important for mitochondrial related functions.

PMID- 22984579
TI  - A p53-Pax2 pathway in kidney development: implications for nephrogenesis.
AB  - Congenital reduction in nephron number (renal hypoplasia) is a predisposing
      factor for chronic kidney disease and hypertension. Despite identification of
      specific genes and pathways in nephrogenesis, determinants of final nephron
      endowment are poorly understood. Here, we report that mice with germ-line p53
      deletion (p53(-/-)) manifest renal hypoplasia; the phenotype can be recapitulated
      by conditional deletion of p53 from renal progenitors in the cap mesenchyme
      (CM(p53-/-)). Mice or humans with germ-line heterozygous mutations in Pax2
      exhibit renal hypoplasia. Since both transcription factors are developmentally
      expressed in the metanephros, we tested the hypothesis that p53 and Pax2
      cooperate in nephrogenesis. In this study, we provide evidence for the presence
      of genetic epistasis between p53 and Pax2: a) p53(-/-) and CM(p53-/-)embryos
      express lower Pax2 mRNA and protein in nephron progenitors than their wild-type
      littermates; b) ChIP-Seq identified peaks of p53 occupancy in chromatin regions
      of the Pax2 promoter and gene in embryonic kidneys; c) p53 binding to Pax2 gene
      is significantly more enriched in Pax2 -expressing than non-expressing
      metanephric mesenchyme cells; d) in transient transfection assays, Pax2 promoter
      activity is stimulated by wild-type p53 and inhibited by a dominant negative
      mutant p53; e) p53 knockdown in cultured metanephric mesenchyme cells down
      regulates endogenous Pax2 expression; f) reduction of p53 gene dosage worsens the
      renal hypoplasia in Pax2(+/-) mice. Bioinformatics identified a set of
      developmental renal genes likely to be co-regulated by p53 and Pax2. We propose
      that the cross-talk between p53 and Pax2 provides a transcriptional platform that
      promotes nephrogenesis, thus contributing to nephron endowment.

PMID- 22984581
TI  - Surveillance and genome analysis of human bocavirus in patients with respiratory
      infection in Guangzhou, China.
AB  - Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract
      diseases and gastrointestinal illness in adult and pediatric patients throughout
      the world. To investigate the epidemiological and genetic variation of HBoV in
      Guangzhou, South China, we screened 3460 throat swab samples from 1686 children
      and 1774 adults with acute respiratory infection symptoms for HBoV between March
      2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV
      strains. Specimens were screened for HBoV by real-time PCR and other 6 common
      respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460
      samples, mostly from pediatric patients (52/58) and inpatient children (47/58).
      Six adult patients were detected as HBoV positive and 5 were emergency cases. Of
      these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus
      (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n =
      7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and
      JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains
      were HBoV1, and were most genetically close to ST2 (GenBank accession number
      DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra
      genotype recombinant strain among HBoV1 variants.

PMID- 22984582
TI  - Mycoepoxydiene inhibits lipopolysaccharide-induced inflammatory responses through
      the suppression of TRAF6 polyubiquitination [corrected].
AB  - Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated
      with mangrove forests. MED has been shown to be able to induce cell cycle arrest
      and cancer cell apoptosis. However, its effects on inflammatory response are
      unclear. Herein we showed that MED exhibited inhibitory effect on inflammatory
      response induced by lipopolysaccharide (LPS). MED significantly inhibited LPS
      induced expression of pro-inflammatory mediators such as tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and nitric oxide (NO) in
      macrophages. MED inhibited LPS-induced nuclear translocation of nuclear factor
      (NF)-kappaB (NF-kappaB) p65, IkappaB degradation, IkappaB kinase (IKK)
      phosphorylation, and the activation of extracellular signal-regulated kinase
      (ERK), c-jun N-terminal kinase (JNK), and p38, suggesting that MED blocks the
      activation of both NF-kappaB and mitogen-activated protein kinase (MAPK)
      pathways. Furthermore, the effects of MED on LPS-induced activation of upstream
      signaling molecules such as transforming growth factor-beta-activated kinase 1
      (TAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1
      receptor associated kinases1 (IRAK1) were investigated. MED significantly
      inhibited TAK1 phosphorylation and TRAF6 polyubiquitination, but not IRAK1
      phosphorylation and TRAF6 dimerization, indicating that MED inhibits LPS-induced
      inflammatory responses at least in part through suppression of TRAF6
      polyubiquitination. Moreover, MED protected mice from LPS-induced endotoxin shock
      by reducing serum inflammatory cytokines. These results suggest that MED is a
      potential lead compound for the development of a novel nonsteroidal anti
      inflammatory drug.

PMID- 22984583
TI  - Annexin a6 modulates chick cranial neural crest cell emigration.
AB  - The vertebrate neural crest is a population of migratory cells that originates in
      the dorsal aspect of the embryonic neural tube. These cells undergo an epithelial
      to-mesenchymal transition (EMT), delaminate from the neural tube and migrate
      extensively to generate an array of differentiated cell types. Elucidating the
      gene regulatory networks involved in neural crest cell induction, migration and
      differentiation are thus crucial to understanding vertebrate development. To this
      end, we have identified Annexin A6 as an important regulator of chick midbrain
      neural crest cell emigration. Annexin proteins comprise a family of calcium
      dependent, membrane-binding molecules that mediate a variety of cellular and
      physiological processes including cell adhesion, migration and invasion. Our data
      indicate that Annexin A6 is expressed in the proper spatio-temporal pattern in
      the chick midbrain to play a potential role in neural crest cell ontogeny. To
      investigate Annexin A6 function, we have depleted or overexpressed Annexin A6 in
      the developing midbrain neural crest cell population. Our results show that knock
      down or overexpression of Annexin A6 reduces or expands the migratory neural
      crest cell domain, respectively. Importantly, this phenotype is not due to any
      change in cell proliferation or cell death but can be correlated with changes in
      the size of the premigratory neural crest cell population and with markers
      associated with EMT. Taken together, our data indicate that Annexin A6 plays a
      pivotal role in modulating the formation of cranial migratory neural crest cells
      during vertebrate development.

PMID- 22984584
TI  - Prevalence and predictors of sub-acute phase disability after injury among
      hospitalised and non-hospitalised groups: a longitudinal cohort study.
AB  - INTRODUCTION: To reduce the burden on injury survivors and their supporters,
      factors associated with poor outcomes need to be identified so that timely post
      injury interventions can be implemented. To date, few studies have investigated
      outcomes for both those who were hospitalised and those who were not. AIM: To
      describe the prevalence and to identify pre-injury and injury-related predictors
      of disability among hospitalised and non-hospitalised people, three months after
      injury. METHODS: Participants in the Prospective Outcomes of Injury Study were
      aged 18-64 years and on an injury entitlement claims register with New Zealand's
      no-fault injury compensation insurer, following referral by healthcare
      professionals. A wide range of pre-injury demographic, health and injury-related
      characteristics were collected at interview. Participants were categorised as
      'hospitalised' if they were placed on New Zealand's National Minimum Data Set
      within seven days of the injury event. Injury severity scores (NISS) and 12
      injury categories were derived from ICD-10 codes. WHODAS assessed disability.
      Multivariable analyses examined relationships between explanatory variables and
      disability. RESULTS: Of 2856 participants, 2752 (96%) had WHODAS scores available
      for multivariable analysis; 673 were hospitalised; 2079 were not. Disability was
      highly prevalent among hospitalised (53.6%) and non-hospitalised (39.4%)
      participants, three-months after injury. In both groups, pre-injury disability,
      obesity and higher injury severity were associated with increased odds of post
      injury disability. A range of other factors were associated with disability in
      only one group: e.g. female, >= 2 chronic conditions and leg fracture among
      hospitalised; aged 35-54 years, trouble accessing healthcare, spine or lower
      extremity sprains/dislocations and assault among non-hospitalised. SIGNIFICANCE:
      Disability was highly prevalent among both groups yet, with a few exceptions,
      factors associated with disability were not common to both groups. Where
      possible, including a range of injured people in studies, hospitalised and not,
      will increase understanding of the burden of disability in the sub-acute phase.

PMID- 22984585
TI  - LAPTM4B allele *2 is associated with breast cancer susceptibility and prognosis.
AB  - BACKGROUND: Lysosome-associated protein transmembrane 4 beta (LAPTM4B) has two
      alleles named LAPTM4B*1 and LAPTM4B*2. Allele *1 contains only one copy of a 19
      bp sequence at the 5'UTR in the first exon, whereas this sequence of allele*2 is
      duplicated and arrayed as a tandem repeat. Previous studies revealed that LAPTM4B
      polymorphisms contribute to the risk of certain types of cancers. This study
      aimed to investigate the polymorphism of LAPTM4B in breast cancer by analysis the
      correlation of LAPTM4B genotype with breast cancer susceptibility,
      clinicopathologic features and prognosis. METHODS: Genotyping of the LAPTM4B
      polymorphism was determined by PCR method. The expression levels of LAPTM4B in
      breast cancer tissues and breast cancer cell lines were determined by
      quantitative reverse-transcription PCR (qRT-PCR) analysis. The correlation of
      LAPTM4B genotype with clinicopathologic parameters and prognosis were assessed
      statistically. RESULTS: The results of qRT-PCR analysis indicated that LAPTM4B*2
      was associated with the higher level of LAPTM4B expression compared with the
      LAPTM4B*1 in both breast cancer cell lines and breast cancer tissues. We found
      that LAPTM4B*2 was associated with an increased risk for breast cancer. LAPTM4B*2
      was significantly associated with higher histopathologic grade, lymph node
      metastasis and poor prognosis. CONCLUSION: LAPTM4B*2 is a risk factor associated
      with breast cancer susceptibility and poor prognosis. LAPTM4B*2 may be a
      potential predicative marker for the susceptibility, progression and metastasis
      of breast cancer.

PMID- 22984586
TI  - Community biomass and bottom up multivariate nutrient complementarity mediate the
      effects of bioturbator diversity on pelagic production.
AB  - Tests of the biodiversity and ecosystem functioning (BEF) relationship have
      focused little attention on the importance of interactions between species
      diversity and other attributes of ecological communities such as community
      biomass. Moreover, BEF research has been mainly derived from studies measuring a
      single ecosystem process that often represents resource consumption within a
      given habitat. Focus on single processes has prevented us from exploring the
      characteristics of ecosystem processes that can be critical in helping us to
      identify how novel pathways throughout BEF mechanisms may operate. Here, we
      investigated whether and how the effects of biodiversity mediated by non-trophic
      interactions among benthic bioturbator species vary according to community
      biomass and ecosystem processes. We hypothesized that (1) bioturbator biomass and
      species richness interact to affect the rates of benthic nutrient regeneration
      [dissolved inorganic nitrogen (DIN) and total dissolved phosphorus (TDP)] and
      consequently bacterioplankton production (BP) and that (2) the complementarity
      effects of diversity will be stronger on BP than on nutrient regeneration because
      the former represents a more integrative process that can be mediated by
      multivariate nutrient complementarity. We show that the effects of bioturbator
      diversity on nutrient regeneration increased BP via multivariate nutrient
      complementarity. Consistent with our prediction, the complementarity effects were
      significantly stronger on BP than on DIN and TDP. The effects of the biomass
      species richness interaction on complementarity varied among the individual
      processes, but the aggregated measures of complementarity over all ecosystem
      processes were significantly higher at the highest community biomass level. Our
      results suggest that the complementarity effects of biodiversity can be stronger
      on more integrative ecosystem processes, which integrate subsidiary "simpler"
      processes, via multivariate complementarity. In addition, reductions in community
      biomass may decrease the strength of interspecific interactions so that the
      enhanced effects of biodiversity on ecosystem processes can disappear well before
      species become extinct.

PMID- 22984587
TI  - Breath pentane as a potential biomarker for survival in hepatic ischemia and
      reperfusion injury--a pilot study.
AB  - BACKGROUND: Exhaled pentane, which is produced as a consequence of reactive
      oxygen species-mediated lipid peroxidation, is a marker of oxidative stress.
      Propofol is widely used as a hypnotic agent in intensive care units and the
      operating room. Moreover, this agent has been reported to inhibit lipid
      peroxidation by directly scavenging reactive oxygen species. In this study, using
      a porcine liver ischemia-reperfusion injury model, we have evaluated the
      hypothesis that high concentrations of breath pentane are related to adverse
      outcome and that propofol could reduce breath pentane and improve liver injury
      and outcome in swine in this situation. METHODOLOGY/PRINCIPAL FINDINGS: Twenty
      male swine were assigned to two groups: propofol (n = 10) and chloral hydrate
      groups (n = 10). Hepatic ischemia was induced by occluding the portal inflow
      vessels. Ischemia lasted for 30 min, followed by reperfusion for 360 min. Exhaled
      and blood pentane concentrations in the chloral hydrate group markedly increased
      1 min after reperfusion and then decreased to baseline. Breath and blood pentane
      concentrations in the propofol group increased 1 min after reperfusion but were
      significantly lower than in the chloral hydrate group. A negative correlation was
      found between breath pentane levels and survival in the chloral hydrate group.
      The median overall survival was 251 min after reperfusion (range 150-360 min) in
      the chloral hydrate group. All of the swine were alive in the propofol group.
      CONCLUSIONS: Monitoring of exhaled pentane may be useful for evaluating the
      severity of hepatic ischemia-reperfusion injury and aid in predicting the
      outcome; propofol may improve the outcome in this situation.

PMID- 22984588
TI  - Airway epithelial cells condition dendritic cells to express multiple immune
      surveillance genes.
AB  - Increasing evidence suggests that crosstalk between airway epithelial cells (AEC)
      and adjacent dendritic cells (DC) tightly regulates airway mucosal DC function in
      steady state. AEC are known to express multiple immuno-modulatory factors, though
      detailed information on how this influences human DC function remains incomplete.
      We recently demonstrated using an in vitro coculture model that AEC alter
      differentiation of monocytes into DC in a manner that inhibits expression of
      potentially damaging Th2 effector function. In the current study, we have
      extended these findings to examine other aspects of DC function. Using micro
      array technology we show that multiple genes important for immune surveillance
      are significantly over expressed in purified AEC-conditioned DC, compared to
      control DC. These findings were confirmed by quantitative real time PCR or flow
      cytometry in an independent sample set. In particular, AEC-conditioned DC showed
      selective upregulation of chemokines that recruit Th1 cells, but minimal change
      in chemokines linked to Th2 cell recruitment. AEC-conditioned DC were also
      characterized by enhanced expression of complement family genes (C1QB, C2, CD59
      and SERPING1), Fcgamma receptor genes (FCGR1A, FCGR2A, FCGR2B and FCGR2C),
      signaling lymphocytic activation molecule family member 1 (SLAM), programmed
      death ligands 1 and 2, CD54 and CD200R1, relative to control DC. These findings
      suggest that AEC conditioning facilitates the capacity of DC to react to danger
      signals, to enhance leukocyte recruitment, especially of Th1 effector cells, and
      to interact with other immune cell populations while minimizing the risks of
      excessive inflammation leading to tissue damage.

PMID- 22984589
TI  - T cell responses induced by adenoviral vectored vaccines can be adjuvanted by
      fusion of antigen to the oligomerization domain of C4b-binding protein.
AB  - Viral vectored vaccines have been shown to induce both T cell and antibody
      responses in animals and humans. However, the induction of even higher level T
      cell responses may be crucial in achieving vaccine efficacy against difficult
      disease targets, especially in humans. Here we investigate the oligomerization
      domain of the alpha-chain of C4b-binding protein (C4 bp) as a candidate T cell
      "molecular adjuvant" when fused to malaria antigens expressed by human adenovirus
      serotype 5 (AdHu5) vectored vaccines in BALB/c mice. We demonstrate that i) C
      terminal fusion of an oligomerization domain can enhance the quantity of antigen
      specific CD4(+) and CD8(+) T cell responses induced in mice after only a single
      immunization of recombinant AdHu5, and that the T cells maintain similar
      functional cytokine profiles; ii) an adjuvant effect is observed for AdHu5
      vectors expressing either the 42 kDa C-terminal domain of Plasmodium yoelii
      merozoite surface protein 1 (PyMSP1(42)) or the 83 kDa ectodomain of P.
      falciparum strain 3D7 apical membrane antigen 1 (PfAMA1), but not a candidate
      128kDa P. falciparum MSP1 biallelic fusion antigen; iii) following two homologous
      immunizations of AdHu5 vaccines, antigen-specific T cell responses are further
      enhanced, however, in both BALB/c mice and New Zealand White rabbits no
      enhancement of functional antibody responses is observed; and iv) that the T cell
      adjuvant activity of C4 bp is not dependent on a functional Fc-receptor gamma
      chain in the host, but is associated with the oligomerization of small (<80 kDa)
      antigens expressed by recombinant AdHu5. The oligomerization domain of C4 bp can
      thus adjuvant T cell responses induced by AdHu5 vectors against selected antigens
      and its clinical utility as well as mechanism of action warrant further
      investigation.

PMID- 22984590
TI  - Phosphoinositide 3-kinase C2beta regulates RhoA and the actin cytoskeleton
      through an interaction with Dbl.
AB  - The regulation of cell morphology is a dynamic process under the control of
      multiple protein complexes acting in a coordinated manner. Phosphoinositide 3
      kinases (PI3K) and their lipid products are widely involved in cytoskeletal
      regulation by interacting with proteins regulating RhoGTPases. Class II PI3K
      isoforms have been implicated in the regulation of the actin cytoskeleton,
      although their exact role and mechanism of action remain to be established. In
      this report, we have identified Dbl, a Rho family guanine nucleotide exchange
      factor (RhoGEF) as an interaction partner of PI3KC2beta. Dbl was co
      immunoprecipitated with PI3KC2beta in NIH3T3 cells and cancer cell lines. Over
      expression of Class II phosphoinositide 3-kinase PI3KC2beta in NIH3T3 fibroblasts
      led to increased stress fibres formation and cell spreading. Accordingly, we
      found high basal RhoA activity and increased serum response factor (SRF)
      activation downstream of RhoA upon serum stimulation. In contrast, the dominant
      negative form of PI3KC2beta strongly reduced cell spreading and stress fibres
      formation, as well as SRF response. Platelet-derived growth factor (PDGF)
      stimulation of wild-type PI3KC2beta over-expressing NIH3T3 cells strongly
      increased Rac and c-Jun N-terminal kinase (JNK) activation, but failed to show
      similar effect in the cells with the dominant-negative enzyme. Interestingly,
      epidermal growth factor (EGF) and PDGF stimulation led to increased extracellular
      signal-regulated kinase (Erk) and Akt pathway activation in cells with elevated
      wild-type PI3KC2beta expression. Furthermore, increased expression of PI3KC2beta
      protected NIH3T3 from detachment-dependent death (anoikis) in a RhoA-dependent
      manner. Taken together, these findings suggest that PI3KC2beta modulates the cell
      morphology and survival through a specific interaction with Dbl and the
      activation of RhoA.

PMID- 22984591
TI  - Heparin-binding EGF-like growth factor induces heart interstitial fibrosis via an
      Akt/mTor/p70s6k pathway.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is essential
      for maintaining normal function of the adult heart and is known to play an
      important role in myocardial remodeling. In the present study, we observed that
      heart-specific HB-EGF transgenic (TG) mice had systolic dysfunction with
      decreased fractional shortening (FS%), increased end-systolic diameter (LVIDs) at
      5 months of age, increased heart fibrosis, and increased mRNA expression of
      Col1alpha1 and Col3alpha1 at 1, 3, 5 and 7 months of age compared to
      nontransgenic (NTG) littermates. However, the left ventricular anterior wall
      thickness at end-systole (LVAWs) of the TG mice was not different than the NTG
      mice. Phosphorylation levels of Akt, mTor and p70s6k were increased due to HB-EGF
      expression in TG mice compared with the NTG mice at 3 and 7 months of age.
      Additionally, activated Akt, mTor and p70s6k were co-localized with vimentin to
      cardiac fibroblasts isolated from TG mice. Furthermore, HB-EGF significantly
      increased phosphorylation levels of Akt, mTor and p70s6k and increased expression
      of type I collagen in cultured primary cardiac fibroblasts. Rapamycin (Rapa) and
      CRM197, inhibitors of mTor and HB-EGF respectively, could inhibit the expression
      of type I collagen in the cultured primary cardiac fibroblasts and Rapa
      suppressed interstitial fibrosis of the heart tissues in vivo. In addition, a
      BrdU assay showed that HB-EGF increased proliferation of cardiac fibroblasts by
      30% compared with cells without HB-EGF treatment. HB-EGF-induced proliferation
      was completely diminished in the presence of Rapa. These results suggest that HB
      EGF induced heart fibrosis and proliferation of cardiac fibroblasts occurs
      through activation of the Akt/mTor/p70s6k pathway.

PMID- 22984592
TI  - Psychological distress, depression, anxiety, and burnout among international
      humanitarian aid workers: a longitudinal study.
AB  - BACKGROUND: International humanitarian aid workers providing care in emergencies
      are subjected to numerous chronic and traumatic stressors. OBJECTIVES: To examine
      consequences of such experiences on aid workers' mental health and how the impact
      is influenced by moderating variables. METHODOLOGY: We conducted a longitudinal
      study in a sample of international non-governmental organizations. Study outcomes
      included anxiety, depression, burnout, and life and job satisfaction. We
      performed bivariate regression analyses at three time points. We fitted
      generalized estimating equation multivariable regression models for the
      longitudinal analyses. RESULTS: Study participants from 19 NGOs were assessed at
      three time points: 212 participated at pre-deployment; 169 (80%) post-deployment;
      and 154 (73%) within 3-6 months after deployment. Prior to deployment, 12 (3.8%)
      participants reported anxiety symptoms, compared to 20 (11.8%) at post-deployment
      (p = 0.0027); 22 (10.4%) reported depression symptoms, compared to 33 (19.5%) at
      post-deployment (p = 0.0117) and 31 (20.1%) at follow-up (p = .00083). History of
      mental illness (adjusted odds ratio [AOR] 4.2; 95% confidence interval [CI] 1.45
      12.50) contributed to an increased risk for anxiety. The experience of
      extraordinary stress was a contributor to increased risk for burnout
      depersonalization (AOR 1.5; 95% CI 1.17-1.83). Higher levels of chronic stress
      exposure during deployment were contributors to an increased risk for depression
      (AOR 1.1; 95% CI 1.02-1.20) comparing post- versus pre-deployment, and increased
      risk for burnout emotional exhaustion (AOR 1.1; 95% CI 1.04-1.19). Social support
      was associated with lower levels of depression (AOR 0.9; 95% CI 0.84-0.95),
      psychological distress (AOR = 0.9; [CI] 0.85-0.97), burnout lack of personal
      accomplishment (AOR 0.95; 95% CI 0.91-0.98), and greater life satisfaction (p =
      0.0213). CONCLUSIONS: When recruiting and preparing aid workers for deployment,
      organizations should consider history of mental illness and take steps to
      decrease chronic stressors, and strengthen social support networks.

PMID- 22984593
TI  - Norcantharidin facilitates LPS-mediated immune responses by up-regulation of
      AKT/NF-kappaB signaling in macrophages.
AB  - Norcantharidin (NCTD), a demethylated analog of cantharidin, is a common used
      clinical drug to inhibit proliferation and metastasis of cancer cells. But the
      role of NCTD in modulating immune responses remains unknown. Here, we
      investigated the function and mechanism of NCTD in regulation of TLR4 associated
      immune response in macrophages. We evaluated the influence of NCTD on host
      defense against invaded pathogens by acute peritonitis mouse model, ELISA, Q-PCR,
      nitrite quantification, phagocytosis assay and gelatin zymography assay. Our data
      showed that the survival and the serum concentrations of IL-6 and TNF-alpha were
      all enhanced by NCTD significantly in peritonitis mouse model. Accordingly, LPS
      induced cytokine, nitric oxide and MMP-9 production as well as the phagocytosis
      of bacteria were all up-regulated by NCTD in a dose dependent manner in both
      RAW264.7 cells and bone marrow-derived macrophages (BMMs). Then we further
      analyzed TLR4 associated signaling pathway by Western blot, Immunofluorescence
      and EMSA in the presence or absence of LPS. The phosphorylation of AKT and p65 at
      serine 536 but not serine 468 was enhanced obviously by NCTD in a dose dependent
      manner, whereas the degradation of IkappaBalpha was little effected.
      Consequently, the nuclear translocation and DNA binding ability of NF-kappaB was
      also increased by NCTD obviously in RAW264.7 cells. Our results demonstrated that
      NCTD could facilitate LPS-mediated immune response through promoting the
      phosphorylation of AKT/p65 and transcriptional activity of NF-kappaB, thus
      reprofiling the traditional anti-tumor drug NCTD as a novel immune regulator in
      promoting host defense against bacterial infection.

PMID- 22984594
TI  - Clues to occult cancer in patients with ischemic stroke.
AB  - BACKGROUND: We hypothesized that hidden malignancy could be detected in patients
      with cryptogenic stroke without active cancer when they showed the distinctive
      characteristics of cancer-related stroke. METHODS AND FINDINGS: Among 2,562
      consecutive patients with acute ischemic stroke, patients with cryptogenic stroke
      were analyzed and categorized into two groups according to the presence of active
      cancer: cryptogenic stroke with active cancer (cancer-related stroke, CA-stroke)
      group and without active cancer (CR-stroke) group. Patients with active lung
      cancer without stroke were also recruited for comparison purposes (CA-control).
      Clinical factors, lesion patterns on diffusion-weighted MRI (DWI), and laboratory
      findings were analyzed among groups. A total of 348 patients with cryptogenic
      stroke were enrolled in this study. Among them, 71 (20.4%) patients had active
      cancer at the time of stroke. The D-dimer levels were significantly higher in
      patients with CA-stroke than those with CR-stroke or CA-control (both p<0.001).
      Regarding lesion patterns, patients with CA-stroke mostly had multiple lesions in
      multiple vascular territories, while more than 80% of patients with CR-stroke had
      single/multiple lesions in a single vascular territory (P<0.001). D-dimer levels
      (OR 1.11 per 1 ug/mL increase; 95% CI 1.06-1.15; P<0.001) and DWI lesion patterns
      (OR 7.13; 95% CI 3.42-14.87; P<0.001) were independently associated with CA
      stroke. Workup for hidden malignancy was performed during hospitalization in 10
      patients who showed elevated D-dimer levels and multiple infarcts involving
      multiple vascular territories but had no known cancer, and it revealed hidden
      malignancies in all the patients. CONCLUSION: Patients with CA-stroke have
      distinctive D-dimer levels and lesion patterns. These characteristics can serve
      as clues to occult cancer in patients with cryptogenic stroke.

PMID- 22984595
TI  - Community impacts of Prosopis juliflora invasion: biogeographic and congeneric
      comparisons.
AB  - We coordinated biogeographical comparisons of the impacts of an exotic invasive
      tree in its native and non-native ranges with a congeneric comparison in the non
      native range. Prosopis juliflora is taxonomically complicated and with P. pallida
      forms the P. juliflora complex. Thus we sampled P. juliflora in its native
      Venezuela, and also located two field sites in Peru, the native range of Prosopis
      pallida. Canopies of Prosopis juliflora, a native of the New World but an invader
      in many other regions, had facilitative effects on the diversity of other species
      in its native Venezuela, and P. pallida had both negative and positive effects
      depending on the year, (overall neutral effects) in its native Peru. However, in
      India and Hawaii, USA, where P. juliflora is an aggressive invader, canopy
      effects were consistently and strongly negative on species richness. Prosopis
      cineraria, a native to India, had much weaker effects on species richness in
      India than P. juliflora. We carried out multiple congeneric comparisons between
      P. juliflora and P. cineraria, and found that soil from the rhizosphere of P.
      juliflora had higher extractable phosphorus, soluble salts and total phenolics
      than P. cineraria rhizosphere soils. Experimentally applied P. juliflora litter
      caused far greater mortality of native Indian species than litter from P.
      cineraria. Prosopis juliflora leaf leachate had neutral to negative effects on
      root growth of three common crop species of north-west India whereas P. cineraria
      leaf leachate had positive effects. Prosopis juliflora leaf leachate also had
      higher concentrations of total phenolics and L-tryptophan than P. cineraria,
      suggesting a potential allelopathic mechanism for the congeneric differences. Our
      results also suggest the possibility of regional evolutionary trajectories among
      competitors and that recent mixing of species from different trajectories has the
      potential to disrupt evolved interactions among native species.

PMID- 22984596
TI  - Identification of novel human dipeptidyl peptidase-IV inhibitors of natural
      origin (part I): virtual screening and activity assays.
AB  - BACKGROUND: There has been great interest in determining whether natural products
      show biological activity toward protein targets of pharmacological relevance. One
      target of particular interest is DPP-IV whose most important substrates are
      incretins that, among other beneficial effects, stimulates insulin biosynthesis
      and secretion. Incretins have very short half-lives because of their rapid
      degradation by DPP-IV and, therefore, inhibiting this enzyme improves glucose
      homeostasis. As a result, DPP-IV inhibitors are of considerable interest to the
      pharmaceutical industry. The main goals of this study were (a) to develop a
      virtual screening process to identify potential DPP-IV inhibitors of natural
      origin; (b) to evaluate the reliability of our virtual-screening protocol by
      experimentally testing the in vitro activity of selected natural-product hits;
      and (c) to use the most active hit for predicting derivatives with higher binding
      affinities for the DPP-IV binding site. METHODOLOGY/PRINCIPAL FINDINGS: We
      predicted that 446 out of the 89,165 molecules present in the natural products
      subset of the ZINC database would inhibit DPP-IV with good ADMET properties.
      Notably, when these 446 molecules were merged with 2,342 known DPP-IV inhibitors
      and the resulting set was classified into 50 clusters according to chemical
      similarity, there were 12 clusters that contained only natural products for which
      no DPP-IV inhibitory activity has been previously reported. Nine molecules from 7
      of these 12 clusters were then selected for in vitro activity testing and 7 out
      of the 9 molecules were shown to inhibit DPP-IV (where the remaining two
      molecules could not be solubilized, preventing the evaluation of their DPP-IV
      inhibitory activity). Then, the hit with the highest activity was used as a lead
      compound in the prediction of more potent derivatives. CONCLUSIONS/SIGNIFICANCE:
      We have demonstrated that our virtual-screening protocol was successful in
      identifying novel lead compounds for developing more potent DPP-IV inhibitors.

PMID- 22984597
TI  - Distinct annular oligomers captured along the assembly and disassembly pathways
      of transthyretin amyloid protofibrils.
AB  - BACKGROUND: Defects in protein folding may lead to severe degenerative diseases
      characterized by the appearance of amyloid fibril deposits. Cytotoxicity in
      amyloidoses has been linked to poration of the cell membrane that may involve
      interactions with amyloid intermediates of annular shape. Although annular
      oligomers have been detected in many amyloidogenic systems, their universality,
      function and molecular mechanisms of appearance are debated.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated with high-resolution in situ
      atomic force microscopy the assembly and disassembly of transthyretin (TTR)
      amyloid protofibrils formed of the native protein by pH shift. Annular oligomers
      were the first morphologically distinct intermediates observed in the TTR
      aggregation pathway. Morphological analysis suggests that they can assemble into
      a double-stack of octameric rings with a 16 +/- 2 nm diameter, and displaying the
      tendency to form linear structures. According to light scattering data coupled to
      AFM imaging, annular oligomers appeared to undergo a collapse type of structural
      transition into spheroid oligomers containing 8-16 monomers. Disassembly of TTR
      amyloid protofibrils also resulted in the rapid appearance of annular oligomers
      but with a morphology quite distinct from that observed in the assembly pathway.
      CONCLUSIONS/SIGNIFICANCE: Our observations indicate that annular oligomers are
      key dynamic intermediates not only in the assembly but also in the disassembly of
      TTR protofibrils. The balance between annular and more compact forms of
      aggregation could be relevant for cytotoxicity in amyloidogenic disorders.

PMID- 22984599
TI  - Bag3-induced autophagy is associated with degradation of JCV oncoprotein, T-Ag.
AB  - JC virus, JCV, is a human neurotropic polyomavirus whose replication in glial
      cells causes the fatal demyelinating disease progressive multifocal
      leukoencephalopathy (PML). In addition, JCV possesses oncogenic activity and
      expression of its transforming protein, large T-antigen (T-Ag), in several
      experimental animals induces tumors of neural origin. Further, the presence of
      JCV DNA and T-Ag have been repeatedly observed in several human malignant tissues
      including primitive neuroectodermal tumors and glioblastomas. Earlier studies
      have demonstrated that Bag3, a member of the Bcl-2-associated athanogene (Bag)
      family of proteins, which is implicated in autophagy and apoptosis, is
      downregulated upon JCV infection of glial cells and that JCV T-Ag is responsible
      for suppressing the activity of the BAG3 promoter. Here, we investigated the
      possible impact of Bag3 on T-Ag expression in JCV-infected human primary glial
      cells as well as in cells derived from T-Ag-induced medulloblastoma in transgenic
      animals. Results from these studies revealed that overexpression of Bag3
      drastically decreases the level of T-Ag expression by inducing the autophagic
      degradation of the viral protein. Interestingly, this event leads to the
      inhibition of JCV infection of glial cells, suggesting that the reduced levels of
      T-antigen seen upon the overexpression of Bag3 has a biological impact on the
      viral lytic cycle. Results from protein-protein interaction studies showed that T
      Ag and Bag3 physically interact with each other through the zinc-finger of T-Ag
      and the proline rich domains of Bag3, and this interaction is important for the
      autophagic degradation of T-Ag. Our observations open a new avenue of research
      for better understanding of virus-host interaction by investigating the interplay
      between T-Ag and Bag3, and their impact on the development of JCV-associated
      diseases.

PMID- 22984598
TI  - Myelin-derived lipids modulate macrophage activity by liver X receptor
      activation.
AB  - Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the
      central nervous system in which macrophages and microglia play a central role.
      Foamy macrophages and microglia, containing degenerated myelin, are abundantly
      found in active multiple sclerosis lesions. Recent studies have described an
      altered macrophage phenotype after myelin internalization. However, it is unclear
      by which mechanisms myelin affects the phenotype of macrophages and how this
      phenotype can influence lesion progression. Here we demonstrate, by using genome
      wide gene expression analysis, that myelin-phagocytosing macrophages have an
      enhanced expression of genes involved in migration, phagocytosis and
      inflammation. Interestingly, myelin internalization also induced the expression
      of genes involved in liver-X-receptor signaling and cholesterol efflux. In vitro
      validation shows that myelin-phagocytosing macrophages indeed have an increased
      capacity to dispose intracellular cholesterol. In addition, myelin suppresses the
      secretion of the pro-inflammatory mediator IL-6 by macrophages, which was
      mediated by activation of liver-X-receptor beta. Our data show that myelin
      modulates the phenotype of macrophages by nuclear receptor activation, which may
      subsequently affect lesion progression in demyelinating diseases such as multiple
      sclerosis.

PMID- 22984600
TI  - L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism
      dependent manner.
AB  - The dipeptide L-carnosine (beta-alanyl-L-histidine) has been described as
      enigmatic: it inhibits growth of cancer cells but delays senescence in cultured
      human fibroblasts and extends the lifespan of male fruit flies. In an attempt to
      understand these observations, the effects of L-carnosine on the model eukaryote,
      Saccharomyces cerevisiae, were examined on account of its unique metabolic
      properties; S. cerevisiae can respire aerobically, but like some tumor cells, it
      can also exhibit a metabolism in which aerobic respiration is down regulated. L
      Carnosine exhibited both inhibitory and stimulatory effects on yeast cells,
      dependent upon the carbon source in the growth medium. When yeast cells were not
      reliant on oxidative phosphorylation for energy generation (e.g. when grown on a
      fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth
      rates in a dose-dependent manner and increased cell death by up to 17%. In
      contrast, in media containing a non-fermentable carbon source in which yeast are
      dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke
      cell death. This latter observation was confirmed in the respiratory yeast,
      Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing
      pathway were treated with L-carnosine, the cells showed resistance to its
      inhibitory effects. These findings suggest that L-carnosine affects cells in a
      metabolism-dependent manner and provide a rationale for its effects on different
      cell types.

PMID- 22984601
TI  - The Drosophila Translational Control Element (TCE) is required for high-level
      transcription of many genes that are specifically expressed in testes.
AB  - To investigate the importance of core promoter elements for tissue-specific
      transcription of RNA polymerase II genes, we examined testis-specific
      transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter
      sequences from 190 genes that are specifically expressed in testes identified a
      10 bp A/T-rich motif that is identical to the translational control element
      (TCE). The TCE functions in the 5' untranslated region of Mst(3)CGP mRNAs to
      repress translation, and it also functions in a heterologous gene to regulate
      transcription. We found that among genes with focused initiation patterns, the
      TCE is significantly enriched in core promoters of genes that are specifically
      expressed in testes but not in core promoters of genes that are specifically
      expressed in other tissues. The TCE is variably located in core promoters and is
      conserved in melanogaster subgroup species, but conservation dramatically drops
      in more distant species. In transgenic flies, short (300-400 bp) genomic regions
      containing a TCE directed testis-specific transcription of a reporter gene.
      Mutation of the TCE significantly reduced but did not abolish reporter gene
      transcription indicating that the TCE is important but not essential for
      transcription activation. Finally, mutation of testis-specific TFIID (tTFIID)
      subunits significantly reduced the transcription of a subset of endogenous TCE
      containing but not TCE-lacking genes, suggesting that tTFIID activity is limited
      to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE
      containing genes. Thus, the TCE is a core promoter element in a subset of genes
      that are specifically expressed in testes. Furthermore, the TCE regulates
      transcription in the context of short genomic regions, from variable locations in
      the core promoter, and both dependently and independently of tTFIID. These
      findings set the stage for determining the mechanism by which the TCE regulates
      testis-specific transcription and understanding the dual role of the TCE in
      translational and transcriptional regulation.

PMID- 22984602
TI  - Dynamic link between histone H3 acetylation and an increase in the functional
      characteristics of human ESC/iPSC-derived cardiomyocytes.
AB  - Cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs) or human
      induced pluripotent stem cells (hiPSCs) are functionally heterogeneous, display
      insufficient biological efficacy and generally possess the electrophysiological
      properties seen in fetal CMs. However, a homogenous population of hESC/hiPSC-CMs,
      with properties similar to those of adult human ventricular cells, is required
      for use in drug cardiotoxicity screening. Unfortunately, despite the requirement
      for the functional characteristics of post-mitotic beating cell aggregates to
      mimic the behavior of mature cardiomyocytes in vitro, few technological
      improvements have been made in this field to date. Previously, we showed that
      culturing hESC-CMs under low-adhesion conditions with cyclic replating confers
      continuous contractility on the cells, leading to a functional increase in
      cardiac gene expression and electrophysiological properties over time. The
      current study reveals that culturing hESC/hiPSC-CMs under non-adhesive culture
      conditions enhances the electrophysiological properties of the CMs through an
      increase in the acetylation of histone H3 lysine residues, as confirmed by
      western blot analyses. Histone H3 acetylation was induced chemically by treating
      primitive hESC/hiPSC-CMs with Trichostatin A (TSA), a histone deacetylase (HDAC)
      inhibitor, resulting in an immediate increase in global cardiac gene expression.
      In functional analyses using multi-electrode array (MEA) recordings, TSA-treated
      hESC/hiPSC-CM colonies showed appropriate responses to particular concentrations
      of known potassium ion channel inhibitors. Thus, the combination of a cell
      autonomous functional increase in response to non-adhesive culture and short-term
      TSA treatment of hESC/hiPSC-CM colonies cultured on MEA electrodes will help to
      make cardiac toxicity tests more accurate and reproducible via genome-wide
      chromatin activation.

PMID- 22984603
TI  - Organotypic brain slice cultures of adult transgenic P301S mice--a model for
      tauopathy studies.
AB  - BACKGROUND: Organotypic brain slice cultures represent an excellent compromise
      between single cell cultures and complete animal studies, in this way replacing
      and reducing the number of animal experiments. Organotypic brain slices are
      widely applied to model neuronal development and regeneration as well as neuronal
      pathology concerning stroke, epilepsy and Alzheimer's disease (AD). AD is
      characterized by two protein alterations, namely tau hyperphosphorylation and
      excessive amyloid beta deposition, both causing microglia and astrocyte
      activation. Deposits of hyperphosphorylated tau, called neurofibrillary tangles
      (NFTs), surrounded by activated glia are modeled in transgenic mice, e.g. the
      tauopathy model P301S. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explore
      the benefits and limitations of organotypic brain slice cultures made of mature
      adult transgenic mice as a potential model system for the multifactorial
      phenotype of AD. First, neonatal (P1) and adult organotypic brain slice cultures
      from 7- to 10-month-old transgenic P301S mice have been compared with regard to
      vitality, which was monitored with the lactate dehydrogenase (LDH)- and the MTT
      (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays over 15
      days. Neonatal slices displayed a constant high vitality level, while the
      vitality of adult slice cultures decreased significantly upon cultivation.
      Various preparation and cultivation conditions were tested to augment the
      vitality of adult slices and improvements were achieved with a reduced slice
      thickness, a mild hypothermic cultivation temperature and a cultivation CO(2)
      concentration of 5%. Furthermore, we present a substantial immunohistochemical
      characterization analyzing the morphology of neurons, astrocytes and microglia in
      comparison to neonatal tissue. CONCLUSION/SIGNIFICANCE: Until now only adolescent
      animals with a maximum age of two months have been used to prepare organotypic
      brain slices. The current study provides evidence that adult organotypic brain
      slice cultures from 7- to 10-month-old mice independently of the transgenic
      modification undergo slow programmed cell death, caused by a dysfunction of the
      neuronal repair systems.

PMID- 22984604
TI  - Progression of cartilage degradation, bone resorption and pain in rat
      temporomandibular joint osteoarthritis induced by injection of iodoacetate.
AB  - BACKGROUND: Osteoarthritis (OA) is an important subtype of temporomandibular
      disorders. A simple and reproducible animal model that mimics the histopathologic
      changes, both in the cartilage and subchondral bone, and clinical symptoms of
      temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of
      its process and underlying mechanism. OBJECTIVE: To explore whether injection of
      monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce
      OA-like lesions. METHODS: Female rats were injected with varied doses of MIA into
      the upper compartment and observed for up to 12 weeks. Histologic, radiographic,
      behavioral, and molecular changes in the TMJ were evaluated by light and electron
      microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR,
      immunohistochemistry, and TUNEL assay. RESULTS: The intermediate zone of the disc
      loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA
      dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4
      weeks. Condylar destruction presented in a time-dependent manner, including
      chondrocyte apoptosis in the early stages, subsequent cartilage matrix
      disorganization and subchondral bone erosion, fibrosis, subchondral bone
      sclerosis, and osteophyte formation in the late stages. Nociceptive responses
      increased in the early stages, corresponding to severe synovitis. Furthermore,
      chondrocyte apoptosis and an imbalance between anabolism and catabolism of
      cartilage and subchondral bone might account for the condylar destruction.
      CONCLUSIONS: Multi-level data demonstrated a reliable and convenient rat model of
      TMJOA could be induced by MIA injection into the upper compartment. The model
      might facilitate TMJOA related researches.

PMID- 22984605
TI  - Group II metabotropic glutamate receptors depress synaptic transmission onto
      subicular burst firing neurons.
AB  - The subiculum (SUB) is a pivotal structure positioned between the hippocampus
      proper and various cortical and subcortical areas. Despite the growing body of
      anatomical and intrinsic electrophysiological data of subicular neurons,
      modulation of synaptic transmission in the SUB is not well understood. In the
      present study we investigated the role of group II metabotropic glutamate
      receptors (mGluRs), which have been shown to be involved in the regulation of
      synaptic transmission by suppressing presynaptic cAMP activity. Using field
      potential and patch-clamp whole cell recordings we demonstrate that glutamatergic
      transmission at CA1-SUB synapses is depressed by group II mGluRs in a cell-type
      specific manner. Application of the group II mGluR agonist (2S,1'R,2'R,3'R)-2-(2,
      3-dicarboxycyclopropyl)glycine (DCG-IV) led to a significantly higher reduction
      of excitatory postsynaptic currents in subicular bursting cells than in regular
      firing cells. We further used low-frequency stimulation protocols and brief high
      frequency bursts to test whether synaptically released glutamate is capable of
      activating presynaptic mGluRs. However, neither frequency facilitation is
      enhanced in the presence of the group II mGluR antagonist LY341495, nor is a test
      stimulus given after a high-frequency burst. In summary, we present
      pharmacological evidence for presynaptic group II mGluRs targeting subicular
      bursting cells, but both low- and high-frequency stimulation protocols failed to
      activate presynaptically located mGluRs.

PMID- 22984606
TI  - Giga-pixel lensfree holographic microscopy and tomography using color image
      sensors.
AB  - We report Giga-pixel lensfree holographic microscopy and tomography using color
      sensor-arrays such as CMOS imagers that exhibit Bayer color filter patterns.
      Without physically removing these color filters coated on the sensor chip, we
      synthesize pixel super-resolved lensfree holograms, which are then reconstructed
      to achieve ~350 nm lateral resolution, corresponding to a numerical aperture of
      ~0.8, across a field-of-view of ~20.5 mm(2). This constitutes a digital image
      with ~0.7 Billion effective pixels in both amplitude and phase channels (i.e.,
      ~1.4 Giga-pixels total). Furthermore, by changing the illumination angle (e.g.,
      +/- 50 degrees ) and scanning a partially-coherent light source across two
      orthogonal axes, super-resolved images of the same specimen from different
      viewing angles are created, which are then digitally combined to synthesize
      tomographic images of the object. Using this dual-axis lensfree tomographic
      imager running on a color sensor-chip, we achieve a 3D spatial resolution of
      ~0.35 um * 0.35 um * ~2 um, in x, y and z, respectively, creating an effective
      voxel size of ~0.03 um(3) across a sample volume of ~5 mm(3), which is equivalent
      to >150 Billion voxels. We demonstrate the proof-of-concept of this lensfree
      optical tomographic microscopy platform on a color CMOS image sensor by creating
      tomograms of micro-particles as well as a wild-type C. elegans nematode.

PMID- 22984607
TI  - Elucidation of a novel pathway through which HDAC1 controls cardiomyocyte
      differentiation through expression of SOX-17 and BMP2.
AB  - Embryonic Stem Cells not only hold a lot of potential for use in regenerative
      medicine, but also provide an elegant and efficient way to study specific
      developmental processes and pathways in mammals when whole animal gene knock out
      experiments fail. We have investigated a pathway through which HDAC1 affects
      cardiovascular and more specifically cardiomyocyte differentiation in ES cells by
      controlling expression of SOX17 and BMP2 during early differentiation. This data
      explains current discrepancies in the role of HDAC1 in cardiovascular
      differentiation and sheds light into a new pathway through which ES cells
      determine cardiovascular cell fate.

PMID- 22984608
TI  - Need, enabling, predisposing, and behavioral determinants of access to
      preventative care in Argentina: analysis of the national survey of risk factors.
AB  - INTRODUCTION: Health care utilization is an important step to disease management,
      providing opportunities for prevention and treatment. Anderson's Health Behavior
      Model has defined utilization by need, predisposing, and enabling determinants.
      We hypothesize that need, predisposing, and enabling, highlighting behavioral
      factors are associated with utilization in Argentina. METHODS: We performed a
      logistic regression analysis of the 2005 and 2009 Argentinean Survey of Risk
      Factors, a cohort of 41,392 and 34,732 individuals, to explore the association
      between need, enabling, predisposing, and behavioral factors to blood pressure
      measurement in the last year. RESULTS: In the 2005 cohort, blood pressure
      measurement was associated with perception of health, insurance coverage, basic
      needs met, and income. Additionally, female sex, civil state, household type,
      older age groups, education, and alcohol use were associated with utilization.
      The 2009 cohort showed similar associations with only minor differences between
      the models. CONCLUSIONS: We explored the association between utilization of
      clinical preventive services with need, enabling, predisposing, and behavioral
      factors. While predisposing and need determinants are associated with
      utilization, enabling factors such as insurance coverage provides an area for
      public intervention. These are important findings where policies should be
      focused to improve utilization of preventive services in Argentina.

PMID- 22984609
TI  - STIM1 regulates platelet-derived growth factor-induced migration and Ca2+ influx
      in human airway smooth muscle cells.
AB  - It is suggested that migration of airway smooth muscle (ASM) cells plays an
      important role in the pathogenesis of airway remodeling in asthma. Increases in
      intracellular Ca(2+) concentrations ([Ca(2+)](i)) regulate most ASM cell
      functions related to asthma, such as contraction and proliferation. Recently,
      STIM1 was identified as a sarcoplasmic reticulum (SR) Ca(2+) sensor that
      activates Orai1, the Ca(2+) channel responsible for store-operated Ca(2+) entry
      (SOCE). We investigated the role of STIM1 in [Ca(2+)](i) and cell migration
      induced by platelet-derived growth factor (PDGF)-BB in human ASM cells. Cell
      migration was assessed by a chemotaxis chamber assay. Human ASM cells express
      STIM1, STIM2, and Orai1 mRNAs. SOCE activated by thapsigargin, an inhibitor of SR
      Ca(2+)-ATPase, was significantly blocked by STIM1 siRNA and Orai1 siRNA but not
      by STIM2 siRNA. PDGF-BB induced a transient increase in [Ca(2+)](i) followed by
      sustained [Ca(2+)](i) elevation. Sustained increases in [Ca(2+)](i) due to PDGF
      BB were significantly inhibited by a Ca(2+) chelating agent EGTA or by siRNA for
      STIM1 or Orai1. The numbers of migrating cells were significantly increased by
      PDGF-BB treatment for 6 h. Knockdown of STIM1 and Orai1 by siRNA transfection
      inhibited PDGF-induced cell migration. Similarly, EGTA significantly inhibited
      PDGF-induced cell migration. In contrast, transfection with siRNA for STIM2 did
      not inhibit the sustained elevation of [Ca(2+)](i) or cell migration induced by
      PDGF-BB. These results demonstrate that STIM1 and Orai1 are essential for PDGF
      induced cell migration and Ca(2+) influx in human ASM cells. STIM1 could be an
      important molecule responsible for airway remodeling.

PMID- 22984610
TI  - Astemizole synergizes calcitriol antiproliferative activity by inhibiting CYP24A1
      and upregulating VDR: a novel approach for breast cancer therapy.
AB  - BACKGROUND: Calcitriol antiproliferative effects include inhibition of the
      oncogenic ether-a-go-go-1 potassium channel (Eag1) expression, which is necessary
      for cell cycle progression and tumorigenesis. Astemizole, a new promising
      antineoplastic drug, targets Eag1 by blocking ion currents. Herein, we
      characterized the interaction between calcitriol and astemizole as well as their
      conjoint antiproliferative action in SUM-229PE, T-47D and primary tumor-derived
      breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Molecular markers were
      studied by immunocytochemistry, Western blot and real time PCR. Inhibitory
      concentrations were determined by dose-response curves and metabolic activity
      assays. At clinically achievable drug concentrations, synergistic
      antiproliferative interaction was observed between calcitriol and astemizole, as
      calculated by combination index analysis (CI <1). Astemizole significantly
      enhanced calcitriol's growth-inhibitory effects (3-11 folds, P<0.01). Mean IC(20)
      values were 1.82 +/- 2.41 nM and 1.62 +/- 0.75 uM; for calcitriol (in estrogen
      receptor negative cells) and astemizole, respectively. Real time PCR showed that
      both drugs alone downregulated, while simultaneous treatment further reduced Ki
      67 and Eag1 gene expression (P<0.05). Astemizole inhibited basal and calcitriol
      induced CYP24A1 and CYP3A4 mRNA expression (cytochromes involved in calcitriol
      and astemizole degradation) in breast and hepatoma cancer cells, respectively,
      while upregulated vitamin D receptor (VDR) expression. CONCLUSIONS/SIGNIFICANCE:
      Astemizole synergized calcitriol antiproliferative effects by downregulating
      CYP24A1, upregulating VDR and targeting Eag1. This study provides insight into
      the molecular mechanisms involved in astemizole-calcitriol combined
      antineoplastic effect, offering scientific support to test both compounds in
      combination in further preclinical and clinical studies of neoplasms expressing
      VDR and Eag1. VDR-negative tumors might also be sensitized to calcitriol
      antineoplastic effects by the use of astemizole. Herein we suggest a novel
      combined adjuvant therapy for the management of VDR/Eag1-expressing breast cancer
      tumors. Since astemizole improves calcitriol bioavailability and activity,
      decreased calcitriol dosing is advised for conjoint administration.

PMID- 22984611
TI  - PET imaging of lung inflammation with [18F]FEDAC, a radioligand for translocator
      protein (18 kDa).
AB  - PURPOSE: The translocator protein (18 kDa) (TSPO) is highly expressed on the
      bronchial and bronchiole epithelium, submucosal glands in intrapulmonary bronchi,
      pneumocytes and alveolar macrophages in human lung. This study aimed to perform
      positron emission tomography (PET) imaging of lung inflammation with
      [(18)F]FEDAC, a specific TSPO radioligand, and to determine cellular sources
      enriching TSPO expression in the lung. METHODS: An acute lung injury model was
      prepared by intratracheal administration of lipopolysaccharide (LPS) to rat.
      Uptake of radioactivity in the rat lungs was measured with small-animal PET after
      injection of [(18)F]FEDAC. Presence of TSPO was examined in the lung tissue using
      Western blot and immunohistochemical assays. RESULTS: The uptake of [(18)F]FEDAC
      increased in the lung with the progress of inflammation by treatment with LPS.
      Pretreatment with a TSPO-selective ligand PK11195 showed a significant decrease
      in the lung uptake of [(18)F]FEDAC due to competitive binding to TSPO. TSPO
      expression was elevated in the inflamed lung section and its level responded to
      the [(18)F]FEDAC uptake and severity of inflammation. Increase of TSPO expression
      was mainly found in the neutrophils and macrophages of inflamed lungs.
      CONCLUSION: From this study we conclude that PET with [(18)F]FEDAC may be a
      useful tool for imaging TSPO expression and evaluating progress of lung
      inflammation. Study on human lung using [(18)F]FEDAC-PET is promising.

PMID- 22984612
TI  - Astrocyte senescence as a component of Alzheimer's disease.
AB  - Aging is the main risk factor for Alzheimer's disease (AD); however, the aspects
      of the aging process that predispose the brain to the development of AD are
      largely unknown. Astrocytes perform a myriad of functions in the central nervous
      system to maintain homeostasis and support neuronal function. In vitro, human
      astrocytes are highly sensitive to oxidative stress and trigger a senescence
      program when faced with multiple types of stress. In order to determine whether
      senescent astrocytes appear in vivo, brain tissue from aged individuals and
      patients with AD was examined for the presence of senescent astrocytes using
      p16(INK4a) and matrix metalloproteinase-1 (MMP-1) expression as markers of
      senescence. Compared with fetal tissue samples (n = 4), a significant increase in
      p16(INK4a)-positive astrocytes was observed in subjects aged 35 to 50 years (n =
      6; P = 0.02) and 78 to 90 years (n = 11; P<10(-6)). In addition, the frontal
      cortex of AD patients (n = 15) harbored a significantly greater burden of
      p16(INK4a)-positive astrocytes compared with non-AD adult control subjects of
      similar ages (n = 25; P = 0.02) and fetal controls (n = 4; P<10(-7)). Consistent
      with the senescent nature of the p16(INK4a)-positive astrocytes, increased
      metalloproteinase MMP-1 correlated with p16(INK4a). In vitro, beta-amyloid 1-42
      (Abeta(1-42)) triggered senescence, driving the expression of p16(INK4a) and
      senescence-associated beta-galactosidase. In addition, we found that senescent
      astrocytes produce a number of inflammatory cytokines including interleukin-6 (IL
      6), which seems to be regulated by p38MAPK. We propose that an accumulation of
      p16(INK4a)-positive senescent astrocytes may link increased age and increased
      risk for sporadic AD.

PMID- 22984614
TI  - Experimental examination of intraspecific density-dependent competition during
      the breeding period in monarch butterflies (Danaus plexippus).
AB  - A central goal of population ecology is to identify the factors that regulate
      population growth. Monarch butterflies (Danaus plexippus) in eastern North
      America re-colonize the breeding range over several generations that result in
      population densities that vary across space and time during the breeding season.
      We used laboratory experiments to measure the strength of density-dependent
      intraspecific competition on egg laying rate and larval survival and then applied
      our results to density estimates of wild monarch populations to model the
      strength of density dependence during the breeding season. Egg laying rates did
      not change with density but larvae at high densities were smaller, had lower
      survival, and weighed less as adults compared to lower densities. Using mean
      larval densities from field surveys resulted in conservative estimates of density
      dependent population reduction that varied between breeding regions and different
      phases of the breeding season. Our results suggest the highest levels of
      population reduction due to density-dependent intraspecific competition occur
      early in the breeding season in the southern portion of the breeding range.
      However, we also found that the strength of density dependence could be almost
      five times higher depending on how many life-stages were used as part of field
      estimates. Our study is the first to link experimental results of a density
      dependent reduction in vital rates to observed monarch densities in the wild and
      show that the effects of density dependent competition in monarchs varies across
      space and time, providing valuable information for developing robust, year-round
      population models in this migratory organism.

PMID- 22984613
TI  - beta3 integrin in cardiac fibroblast is critical for extracellular matrix
      accumulation during pressure overload hypertrophy in mouse.
AB  - The adhesion receptor beta3 integrin regulates diverse cellular functions in
      various tissues. As beta3 integrin has been implicated in extracellular matrix
      (ECM) remodeling, we sought to explore the role of beta3 integrin in cardiac
      fibrosis by using wild type (WT) and beta3 integrin null (beta3-/-) mice for in
      vivo pressure overload (PO) and in vitro primary cardiac fibroblast phenotypic
      studies. Compared to WT mice, beta3-/- mice upon pressure overload hypertrophy
      for 4 wk by transverse aortic constriction (TAC) showed a substantially reduced
      accumulation of interstitial fibronectin and collagen. Moreover, pressure
      overloaded LV from beta3-/- mice exhibited reduced levels of both fibroblast
      proliferation and fibroblast-specific protein-1 (FSP1) expression in early time
      points of PO. To test if the observed impairment of ECM accumulation in beta3-/-
      mice was due to compromised cardiac fibroblast function, we analyzed primary
      cardiac fibroblasts from WT and beta3-/- mice for adhesion to ECM proteins, cell
      spreading, proliferation, and migration in response to platelet derived growth
      factor-BB (PDGF, a growth factor known to promote fibrosis) stimulation. Our
      results showed that beta3-/- cardiac fibroblasts exhibited a significant
      reduction in cell-matrix adhesion, cell spreading, proliferation and migration.
      In addition, the activation of PDGF receptor associated tyrosine kinase and non
      receptor tyrosine kinase Pyk2, upon PDGF stimulation were impaired in beta3-/-
      cells. Adenoviral expression of a dominant negative form of Pyk2 (Y402F) resulted
      in reduced accumulation of fibronectin. These results indicate that beta3
      integrin-mediated Pyk2 signaling in cardiac fibroblasts plays a critical role in
      PO-induced cardiac fibrosis.

PMID- 22984615
TI  - Paternal age and risk of autism in an ethnically diverse, non-industrialized
      setting: Aruba.
AB  - OBJECTIVE: The aim of this study was to examine paternal age in relation to risk
      of autism spectrum disorders (ASDs) in a setting other than the industrialized
      west. DESIGN: A case-control study of Aruban-born children (1990-2003). Cases (N
      = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only
      such clinic in Aruba; gender and age matched controls (N = 347) were gathered
      from public health records. Parental age was defined categorically (<= 29, 30-39,
      40-49, >= 50 y). The analysis was made, using conditional logistic regression.
      RESULTS: Advanced paternal age was associated with increased risk of ASDs in
      offspring. In comparison to the youngest paternal age group (<= 29 y), risk of
      autism increased 2.18 times for children born from fathers in their thirties,
      2.71 times for fathers in their forties, and 3.22 thereafter. CONCLUSION: This
      study, part of the first epidemiologic study of autism in the Caribbean,
      contributes additional evidence, from a distinctive sociocultural setting, of the
      risk of ASD associated with increased paternal age.

PMID- 22984616
TI  - Interspecific variation in compensatory regrowth to herbivory associated with
      soil nutrients in three Ficus (Moraceae) saplings.
AB  - Plant compensatory regrowth is an induced process that enhances plant tolerance
      to herbivory. Plant behavior against herbivores differs between species and
      depends on resource availability, thus making general predictions related to
      plant compensatory regrowth difficult. To understand how soil nutrients determine
      the degree of compensatory regrowth for different plant species, we selected
      saplings of three Ficus species and treated with herbivore insects and artificial
      injury in both glasshouse conditions and in the field at two soil nutrient
      levels. Compensatory regrowth was calculated by biomass, relative growth rate and
      photosynthetic characteristics. A similar pattern was found in both the
      glasshouse and in the field for species F. hispida, where overcompensatory
      regrowth was triggered only under fertile conditions, and full compensatory
      regrowth occurred under infertile conditions. For F. auriculata, overcompensatory
      regrowth was stimulated only under infertile conditions and full compensatory
      regrowth occurred under fertile conditions. Ficus racemosa displayed full
      compensatory regrowth in both soil nutrient levels, but without overcompensatory
      regrowth following any of the treatments. The three Ficus species differed in
      biomass allocation following herbivore damage and artificial injury. The
      root/shoot ratio of F. hispida decreased largely following herbivore damage and
      artificial injury, while the root/shoot ratio for F. auriculata increased against
      damage treatments. The increase of shoot and root size for F. hispida and F.
      auriculata, respectively, appeared to be caused by a significant increase in
      photosynthesis. The results indicated that shifts in biomass allocation and
      increased photosynthesis are two of the mechanisms underlying compensatory
      regrowth. Contrasting patterns among the three Ficus species suggest that further
      theoretical and empirical work is necessary to better understand the complexity
      of the plant responses to herbivore damage.

PMID- 22984617
TI  - Partial absence of pleuropericardial membranes in Tbx18- and Wt1-deficient mice.
AB  - The pleuropericardial membranes are fibro-serous walls that separate the
      pericardial and pleural cavities and anchor the heart inside the mediastinum.
      Partial or complete absence of pleuropericardial membranes is a rare human
      disease, the etiology of which is poorly understood. As an attempt to better
      understand these defects, we wished to analyze the cellular and molecular
      mechanisms directing the separation of pericardial and pleural cavities by
      pleuropericardial membranes in the mouse. We found by histological analyses that
      both in Tbx18- and Wt1-deficient mice the pleural and pericardial cavities
      communicate due to a partial absence of the pleuropericardial membranes in the
      hilus region. We trace these defects to a persisting embryonic connection between
      these cavities, the pericardioperitoneal canals. Furthermore, we identify
      mesenchymal ridges in the sinus venosus region that tether the growing
      pleuropericardial membranes to the hilus of the lung, and thus, close the
      pericardioperitoneal canals. In Tbx18-deficient embryos these mesenchymal ridges
      are not established, whereas in Wt1-deficient embryos the final fusion process
      between these tissues and the body wall does not occur. We suggest that this
      fusion is an active rather than a passive process, and discuss the interrelation
      between closure of the pericardioperitoneal canals, lateral release of the
      pleuropericardial membranes from the lateral body wall, and sinus horn
      development.

PMID- 22984618
TI  - Cross-taxa similarities in affect-induced changes of vocal behavior and voice in
      arboreal monkeys.
AB  - Measuring the affective state of an individual across species with comparable non
      invasive methods is a current challenge in animal communication research. This
      study aims to explore to which extent affect intensity is conveyed in the vocal
      behaviours of three nonhuman primate species (Campbell's monkeys, De Brazza's
      monkeys, red-capped mangabeys), which vary in body size, ecological niche and
      social system. Similarly in the three species, we experimentally induced a change
      in captive social groups' affect by locking all group members together in their
      outside enclosure. The two experimental conditions which varied in affect
      intensity consisted in imposing a pre-reunion 90 mn-separation by splitting up
      the respective group into two subgroups (High affect condition) or not (Low
      affect condition). We measured call rates as well as voice features at the time
      of reunion in both conditions. The three studied species reacted in a very
      similar way. Across species, call rates changed significantly between the
      behaviourally defined states. Furthermore, contact call duration and, to some
      extent, voice pitch increased. Our results suggest, for the first time in
      arboreal Old World monkeys, that affect intensity is conveyed reliably in vocal
      behaviour and specific acoustic characteristics of voice, irrespective of body
      size and ecological niche differences between species. Cross-taxa similarities in
      acoustic cues of affect intensity point to phylogenetic constraints and
      inheritance from a common ancestor, whereas variations in vocal behaviour and
      affect intensity-related acoustic cues between species may be an adaptation to
      specific social requirements and depend on social systems. Our findings as well
      as a comparison with published works on acoustic communication in other
      vertebrate groups support the hypothesis that affect intensity in human voice
      originates from precursors already found deep inside the vertebrate phylogeny.

PMID- 22984619
TI  - Runx1 and Runx3 are involved in the generation and function of highly suppressive
      IL-17-producing T regulatory cells.
AB  - CD4(+)Foxp3(+) T regulatory cells (Tregs) display phenotypic and functional
      plasticity that is regulated by cytokines and other immune cells. Previously, we
      determined that during co-culture with CD4(+)CD25(-) T cells and antigen
      presenting cells, Tregs produced IL-17. Here, we investigated the mechanisms
      underlying the differentiation of IL-17-producing Treg (Tr17) cells and their
      molecular and functional properties. We determined that during stimulation via
      TCR/CD3 and CD28, the combination of IL-1beta and IL-2 was necessary and
      sufficient for the generation of Tr17 cells. Tr17 cells expressed Runx1
      transcription factor, which was required for sustained expression of Foxp3 and
      RORgammat and for production of IL-17. Surprisingly, Tr17 cells also expressed
      Runx3, which regulated transcription of perforin and granzyme B thereby mediating
      cytotoxic activity. Our studies indicate that Tr17 cells concomitantly express
      Foxp3, RORgammat, Runx1 and Runx3 and are capable of producing IL-17 while
      mediating potent suppressive and cytotoxic function.

PMID- 22984620
TI  - Prepulse inhibition of acoustic startle reflex as a function of the frequency
      difference between prepulse and background sounds in mice.
AB  - BACKGROUND: Prepulse inhibition (PPI) depicts the effects of a weak sound
      preceding strong acoustic stimulus on acoustic startle response (ASR). Previous
      studies suggest that PPI is influenced by physical parameters of prepulse sound
      such as intensity and preceding time. The present study characterizes the impact
      of prepulse tone frequency on PPI. METHODS: Seven female C57BL mice were used in
      the present study. ASR was induced by a 100 dB SPL white noise burst. After
      assessing the effect of background sounds (white noise and pure tones) on ASR,
      PPI was tested by using prepulse pure tones with the background tone of either 10
      or 18 kHz. The inhibitory effect was assessed by measuring and analyzing the
      changes in the first peak-to-peak magnitude, root mean square value, duration and
      latency of the ASR as the function of frequency difference between prepulse and
      background tones. RESULTS: Our data showed that ASR magnitude with pure tone
      background varied with tone frequency and was smaller than that with white noise
      background. Prepulse tone systematically reduced ASR as the function of the
      difference in frequency between prepulse and background tone. The 0.5 kHz
      difference appeared to be a prerequisite for inducing substantial ASR inhibition.
      The frequency dependence of PPI was similar under either a 10 or 18 kHz
      background tone. CONCLUSION: PPI is sensitive to frequency information of the
      prepulse sound. However, the critical factor is not tone frequency itself, but
      the frequency difference between the prepulse and background tones.

PMID- 22984621
TI  - Insect Innate Immunity Database (IIID): an annotation tool for identifying immune
      genes in insect genomes.
AB  - The innate immune system is an ancient component of host defense. Since innate
      immunity pathways are well conserved throughout many eukaryotes, immune genes in
      model animals can be used to putatively identify homologous genes in newly
      sequenced genomes of non-model organisms. With the initiation of the "i5k"
      project, which aims to sequence 5,000 insect genomes by 2016, many novel insect
      genomes will soon become publicly available, yet few annotation resources are
      currently available for insects. Thus, we developed an online tool called the
      Insect Innate Immunity Database (IIID) to provide an open access resource for
      insect immunity and comparative biology research
      (http://www.vanderbilt.edu/IIID). The database provides users with simple
      exploratory tools to search the immune repertoires of five insect models
      (including Nasonia), spanning three orders, for specific immunity genes or genes
      within a particular immunity pathway. As a proof of principle, we used an initial
      database with only four insect models to annotate potential immune genes in the
      parasitoid wasp genus Nasonia. Results specify 306 putative immune genes in the
      genomes of N. vitripennis and its two sister species N. giraulti and N.
      longicornis. Of these genes, 146 were not found in previous annotations of
      Nasonia immunity genes. Combining these newly identified immune genes with those
      in previous annotations, Nasonia possess 489 putative immunity genes, the largest
      immune repertoire found in insects to date. While these computational predictions
      need to be complemented with functional studies, the IIID database can help
      initiate and augment annotations of the immune system in the plethora of insect
      genomes that will soon become available.

PMID- 22984622
TI  - SVMTriP: a method to predict antigenic epitopes using support vector machine to
      integrate tri-peptide similarity and propensity.
AB  - Identifying protein surface regions preferentially recognizable by antibodies
      (antigenic epitopes) is at the heart of new immuno-diagnostic reagent discovery
      and vaccine design, and computational methods for antigenic epitope prediction
      provide crucial means to serve this purpose. Many linear B-cell epitope
      prediction methods were developed, such as BepiPred, ABCPred, AAP, BCPred,
      BayesB, BEOracle/BROracle, and BEST, towards this goal. However, effective
      immunological research demands more robust performance of the prediction method
      than what the current algorithms could provide. In this work, a new method to
      predict linear antigenic epitopes is developed; Support Vector Machine has been
      utilized by combining the Tri-peptide similarity and Propensity scores (SVMTriP).
      Applied to non-redundant B-cell linear epitopes extracted from IEDB, SVMTriP
      achieves a sensitivity of 80.1% and a precision of 55.2% with a five-fold cross
      validation. The AUC value is 0.702. The combination of similarity and propensity
      of tri-peptide subsequences can improve the prediction performance for linear B
      cell epitopes. Moreover, SVMTriP is capable of recognizing viral peptides from a
      human protein sequence background. A web server based on our method is
      constructed for public use. The server and all datasets used in the current study
      are available at http://sysbio.unl.edu/SVMTriP.

PMID- 22984623
TI  - The mTOR inhibitor rapamycin has limited acute anticonvulsant effects in mice.
AB  - OBJECTIVE: The mammalian target of rapamycin (mTOR) pathway integrates signals
      from different nutrient sources, including amino acids and glucose. Compounds
      that inhibit mTOR kinase activity such as rapamycin and everolimus can suppress
      seizures in some chronic animal models and in patients with tuberous sclerosis.
      However, it is not known whether mTOR inhibitors exert acute anticonvulsant
      effects in addition to their longer term antiepileptogenic effects. To gain
      insights into how rapamycin suppresses seizures, we investigated the
      anticonvulsant activity of rapamycin using acute seizure tests in mice. METHODS:
      Following intraperitoneal injection of rapamycin, normal four-week-old male NIH
      Swiss mice were evaluated for susceptibility to a battery of acute seizure tests
      similar to those currently used to screen potential therapeutics by the US NIH
      Anticonvulsant Screening Program. To assess the short term effects of rapamycin,
      mice were seizure tested in <= 6 hours of a single dose of rapamycin, and for
      longer term effects of rapamycin, mice were tested after 3 or more daily doses of
      rapamycin. RESULTS: The only seizure test where short-term rapamycin treatment
      protected mice was against tonic hindlimb extension in the MES threshold test,
      though this protection waned with longer rapamycin treatment. Longer term
      rapamycin treatment protected against kainic acid-induced seizure activity, but
      only at late times after seizure onset. Rapamycin was not protective in the 6 Hz
      or PTZ seizure tests after short or longer rapamycin treatment times. In contrast
      to other metabolism-based therapies that protect in acute seizure tests,
      rapamycin has limited acute anticonvulsant effects in normal mice. SIGNIFICANCE:
      The efficacy of rapamycin as an acute anticonvulsant agent may be limited.
      Furthermore, the combined pattern of acute seizure test results places rapamycin
      in a third category distinct from both fasting and the ketogenic diet, and which
      is more similar to drugs acting on sodium channels.

PMID- 22984624
TI  - Deep sequencing of the transcriptomes of soybean aphid and associated
      endosymbionts.
AB  - BACKGROUND: The soybean aphid has significantly impacted soybean production in
      the U.S. Transcriptomic analyses were conducted for further insight into leads
      for potential novel management strategies. METHODOLOGY/PRINCIPAL FINDINGS:
      Transcriptomic data were generated from whole aphids and from 2,000 aphid guts
      using an Illumina GAII sequencer. The sequence data were assembled de novo using
      the Velvet assembler. In addition to providing a general overview, we demonstrate
      (i) the use of the Multiple-k/Multiple-C method for de novo assembly of short
      read sequences, followed by BLAST annotation of contigs for increased transcript
      identification: From 400,000 contigs analyzed, 16,257 non-redundant BLAST hits
      were identified; (ii) analysis of species distributions of top non-redundant
      hits: 80% of BLAST hits (minimum e-value of 1.0-E3) were to the pea aphid or
      other aphid species, representing about half of the pea aphid genes; (iii)
      comparison of relative depth of sequence coverage to relative transcript
      abundance for genes with high (membrane alanyl aminopeptidase N) or low
      transcript abundance; (iv) analysis of the Buchnera transcriptome: Transcripts
      from 57.6% of the genes from Buchnera aphidicola were identified; (v)
      identification of Arsenophonus and Wolbachia as potential secondary
      endosymbionts; (vi) alignment of full length sequences from RNA-seq data for the
      putative salivary gland protein C002, the silencing of which has potential for
      aphid management, and the putative Bacillus thuringiensis Cry toxin receptors,
      aminopeptidase N and alkaline phosphatase. CONCLUSIONS/SIGNIFICANCE: THIS STUDY
      PROVIDES THE MOST COMPREHENSIVE DATA SET TO DATE FOR SOYBEAN APHID GENE
      EXPRESSION: This work also illustrates the utility of short-read transcriptome
      sequencing and the Multiple-k/Multiple-C method followed by BLAST annotation for
      rapid identification of target genes for organisms for which reference genome
      sequences are not available, and extends the utility to include the
      transcriptomes of endosymbionts.

PMID- 22984625
TI  - Novel effects of hormonal contraceptive use on the plasma proteome.
AB  - BACKGROUND: Hormonal contraceptive (HC) use may increase cardiometabolic risk;
      however, the effect of HC on emerging cardiometabolic and other disease risk
      factors is not clear. OBJECTIVES: To determine the association between HC use and
      plasma proteins involved in established and emerging disease risk pathways.
      METHOD: Concentrations of 54 high-abundance plasma proteins were measured
      simultaneously by LC-MRM/MS in 783 women from the Toronto Nutrigenomics and
      Health Study. C-reactive protein (CRP) was measured separately. ANCOVA was used
      to test differences in protein concentrations between users and non-users, and
      among HC users depending on total hormone dose. Linear regression was used to
      test the association between duration (years) of HC use and plasma protein
      concentrations. Principal components analysis (PCA) was used to identify plasma
      proteomic profiles in users and non-users. RESULTS: After Bonferroni correction,
      19 proteins involved in inflammation, innate immunity, coagulation and blood
      pressure regulation were significantly different between users and non-users
      (P<0.0009). These differences were replicated across three distinct ethnocultural
      groups. Traditional markers of glucose and lipid metabolism were also
      significantly higher among HC users. Neither hormone dose nor duration of use
      affected protein concentrations. PCA identified 4 distinct proteomic profiles in
      users and 3 in non-users. CONCLUSION: HC use was associated with different
      concentrations of plasma proteins along various disease-related pathways, and
      these differences were present across different ethnicities. Aside from the known
      effect of HC on traditional biomarkers of cardiometabolic risk, HC use also
      affects numerous proteins that may be biomarkers of dysregulation in
      inflammation, coagulation and blood pressure.

PMID- 22984626
TI  - ABO blood group is associated with response to inhaled nitric oxide in neonates
      with respiratory failure.
AB  - BACKGROUND: Inhaled nitric oxide (iNO) reduces death or need for extracorporeal
      membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of
      the newborn (PPHN). However, the response to iNO is variable and only 50-60% of
      infants demonstrate a response to iNO. It is not known why only some infants
      respond to iNO. Adults and children with blood groups B or AB do not respond as
      well to iNO as those with blood groups O/A. METHODS/PRINCIPAL FINDINGS: To
      determine if blood group was associated with iNO response in newborn infants, a
      retrospective medical record review was done of infants admitted to a regional
      NICU from 2002-9 with a diagnosis of PPHN. Data were collected during the first
      twelve hours post-initiation of treatment. Of 86 infants diagnosed with PPHN, 23
      infants had blood group A [18 received iNO], 21 had group B [18 with iNO], 40 had
      group O [36 with iNO], and 2 had group AB [both received iNO]. Change in
      PaO(2)/FiO(2) was less in infants with blood group A, of whom less than half were
      responders (DeltaPaO(2)/FiO(2)>20%) at 12 h versus 90% of infants with either O
      or B. Race, sex, birth weight, gestational age, Apgar scores at 1 and 5 minutes,
      and baseline PaO(2)/FiO(2) were similar among groups. Outcomes including need for
      ECMO, death, length of ventilatory support, length of iNO use, and hospital stay
      were statistically not different by blood groups. CONCLUSIONS/SIGNIFICANCE: Our
      results indicate that blood group influences iNO response in neonates. We
      hypothesize that either there is genetic linkage of the ABO gene locus with
      vasoregulatory genes, or that blood group antigens directly affect vascular
      reactivity.

PMID- 22984627
TI  - Sampling for microsatellite-based population genetic studies: 25 to 30
      individuals per population is enough to accurately estimate allele frequencies.
AB  - One of the most common questions asked before starting a new population genetic
      study using microsatellite allele frequencies is "how many individuals do I need
      to sample from each population?" This question has previously been answered by
      addressing how many individuals are needed to detect all of the alleles present
      in a population (i.e. rarefaction based analyses). However, we argue that
      obtaining accurate allele frequencies and accurate estimates of diversity are
      much more important than detecting all of the alleles, given that very rare
      alleles (i.e. new mutations) are not very informative for assessing genetic
      diversity within a population or genetic structure among populations. Here we
      present a comparison of allele frequencies, expected heterozygosities and genetic
      distances between real and simulated populations by randomly subsampling 5-100
      individuals from four empirical microsatellite genotype datasets (Formica
      lugubris, Sciurus vulgaris, Thalassarche melanophris, and Himantopus
      novaezelandia) to create 100 replicate datasets at each sample size. Despite
      differences in taxon (two birds, one mammal, one insect), population size, number
      of loci and polymorphism across loci, the degree of differences between simulated
      and empirical dataset allele frequencies, expected heterozygosities and pairwise
      F(ST) values were almost identical among the four datasets at each sample size.
      Variability in allele frequency and expected heterozygosity among replicates
      decreased with increasing sample size, but these decreases were minimal above
      sample sizes of 25 to 30. Therefore, there appears to be little benefit in
      sampling more than 25 to 30 individuals per population for population genetic
      studies based on microsatellite allele frequencies.

PMID- 22984628
TI  - Altered T-cell responses by the periodontal pathogen Porphyromonas gingivalis.
AB  - Several studies support an association between the chronic inflammatory diseases
      periodontitis and atherosclerosis with a crucial role for the periodontal
      pathogen Porphyromonas gingivalis. However, the interplay between this pathogen
      and the adaptive immune system, including T-cells, is sparsely investigated. Here
      we used Jurkat T-cells to determine the effects of P. gingivalis on T-cell
      mediated adaptive immune responses. We show that viable P. gingivalis targets IL
      2 expression at the protein level. Initial cellular events, including ROS
      production and [Ca(2+)](i), were elevated in response to P. gingivalis, but AP-1
      and NF-kappaB activity dropped below basal levels and T-cells were unable to
      sustain stable IL-2 accumulation. IL-2 was partially restored by Leupeptin, but
      not by Cathepsin B Inhibitor, indicating an involvement of Rgp proteinases in the
      suppression of IL-2 accumulation. This was further confirmed by purified Rgp that
      caused a dose-dependent decrease in IL-2 levels. These results provide new
      insights of how this periodontal pathogen evades the host adaptive immune system
      by inhibiting IL-2 accumulation and thus attenuating T-cell proliferation and
      cellular communication.

PMID- 22984629
TI  - Dietary transforming growth factor-beta 2 (TGF-beta2) supplementation reduces
      methotrexate-induced intestinal mucosal injury in a rat.
AB  - BACKGROUND/AIMS: Dietary supplementation with transforming growth factor-beta
      (TGF-beta) has been proven to minimize intestinal damage and facilitate
      regeneration after mucosal injury. In the present study, we evaluated the effects
      of oral TGF-beta2 supplementation on intestinal structural changes, enterocyte
      proliferation and apoptosis following methotrexate (MTX)-induced intestinal
      damage in a rat and in a cell culture model. METHODS: Caco-2 cells were treated
      with MTX and were incubated with increasing concentrations of TGF-beta2. Cell
      apoptosis was assessed using FACS analysis by annexin staining and cell viability
      was monitored using Trypan Blue assay. Male rats were divided into four
      experimental groups: Control rats, CONTR- TGF-beta rats were treated with diet
      enriched with TGF-beta2, MTX rats were treated with a single dose of
      methotrexate, and MTX- TGF-beta rats were treated with diet enriched with TGF
      beta2. Intestinal mucosal damage, mucosal structural changes, enterocyte
      proliferation and enterocyte apoptosis were determined at sacrifice. Real Time
      PCR and Western blot were used to determine bax and bcl-2 mRNA, p-ERK, beta
      catenin, IL-1B and bax protein expression. RESULTS: Treatment of MTX-pretreated
      Caco-2 cells with TGF-B2 resulted in increased cell viability and decreased cell
      apoptosis. Treatment of MTX-rats with TGF-beta2 resulted in a significant
      increase in bowel and mucosal weight, DNA and protein content, villus-height
      (ileum), crypt-depth (jejunum), decreased intestinal-injury score, decreased
      level of apoptosis and increased cell proliferation in jejunum and ileum compared
      to the untreated MTX group. MTX-TGF-beta2 rats demonstrated a lower bax mRNA and
      protein levels as well as increased bcl-2 mRNA levels in jejunum and ileum
      compared to MTX group. Treatment with TGF-beta2 also led to increased pERK, IL-1B
      and beta-catenin protein levels in intestinal mucosa. CONCLUSIONS: Treatment with
      TGF-beta2 prevents mucosal-injury, enhances p-ERK and beta-catenin induced
      enterocyte proliferation, inhibits enterocyte apoptosis and improves intestinal
      recovery following MTX-induced intestinal-mucositis in rats.

PMID- 22984630
TI  - Prostanoid receptors involved in regulation of the beating rate of neonatal rat
      cardiomyocytes.
AB  - Although prostanoids are known to be involved in regulation of the spontaneous
      beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of
      prostanoid receptors have not been investigated in detail. In our experiments,
      prostaglandin (PG)F(2alpha) and prostanoid FP receptor agonists (fluprostenol,
      latanoprost and cloprostenol) produced a decrease in the beating rate. Two
      prostanoid IP receptor agonists (iloprost and beraprost) induced first a marked
      drop in the beating rate and then definitive abrogation of beating. In contrast,
      the prostanoid DP receptor agonists (PGD(2) and BW245C) and TP receptor agonists
      (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP(1)
      and EP(3) receptor agonist) induced marked increases in the beating rate, which
      were suppressed by SC-19220 (a selective prostanoid EP(1) antagonist). Butaprost
      (a selective prostanoid EP(2) receptor agonist), misoprostol (a prostanoid EP(2)
      and EP(3) receptor agonist), 11-deoxy-PGE(1) (a prostanoid EP(2), EP(3) and EP(4)
      receptor agonist) did not alter the beating rate. Our results strongly suggest
      that prostanoid EP(1) receptors are involved in positive regulation of the
      beating rate. Prostanoid EP(1) receptor expression was confirmed by western
      blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express
      both prostanoid IP and FP receptors (which negatively regulate the spontaneous
      beating rate) and prostanoid TP, DP(1) and EP(1) receptors (which positively
      regulate the spontaneous beating rate).

PMID- 22984632
TI  - Aggregation Kinetics of Metal Chalcogenide Nanocrystals: Generation of
      Transparent CdSe(ZnS) Core(shell) Gels.
AB  - Transparent CdSe(ZnS) sol-gel materials have potential uses in optoelectronic
      applications such as light emitting diodes (LEDs) due to their strong
      luminescence properties and the potential for charge transport through the
      prewired nanocrystal (NC) network of the gel. However, typical syntheses of metal
      chalcogenide gels yield materials with poor transparency. In this work, the
      mechanism and kinetics of aggregation of two sizes of CdSe(ZnS) core(shell) NCs,
      initiated by removal of surface thiolate ligands using tetranitromethane (TNM) as
      an oxidant, were studied by means of time-resolved dynamic light scattering
      (TRDLS); the characteristics of the resultant gels were probed by optical
      absorption, transmission electron microscopy (TEM) and small angle X-ray
      scattering (SAXS). At low concentrations of NCs (ca. 4 * 10(-7) M), the smaller,
      green-emitting NCs aggregate faster than the larger, orange-emitting NCs, for a
      specific oxidant concentration. The kinetics of aggregation have a significant
      impact on the macroscopic properties (i.e. transparency) of the resultant gels,
      with the transparency of the gels decreasing with the increase of oxidant
      concentration due the formation of larger clusters at the gel point and a shift
      away from a reaction limited cluster aggregation (RLCA) mechanism. This is
      further confirmed by the analyses of the gel structures by SAXS and TEM.
      Likewise, the larger orange-emitting particles also produce larger aggregates at
      the gel point, leading to lower transparency. The ability to control the
      transparency of chalcogenide gels will enable their properties to be tuned in
      order to address application-specific needs in optoelectronics.

PMID- 22984631
TI  - LAPTM4B allele *2 is a marker of poor prognosis for gallbladder carcinoma.
AB  - BACKGROUND: Lysosomal protein transmembrane 4 beta (LAPTM4B) is a novel cancer
      related gene which has two alleles designated LAPTM4B*1 and LAPTM4B*2. In this
      study we investigated the correlation of LAPTM4B genotype with prognosis and
      clinicopathologic features in patients who had undergone curative resection for
      gallbladder carcinoma (GBC). METHODOLOGY/PRINCIPAL FINDINGS: PCR assay was
      performed to determine the LAPTM4B genotype in 85 patients. The correlation of
      LAPTM4B genotype with clinicopathologic parameters was assessed with the Chi
      squared test. Differences in patient survival were determined by the Kaplan-Meier
      method. Multivariate analysis of prognostic factors was carried out with Cox
      regression analysis. Patients with LAPTM4B *2 had both significantly shorter
      overall survival (OS) and shorter disease-free survival (DFS) (both P<0.001).
      Multivariate analysis showed that LAPTM4B genotype is a prognostic factor for OS
      and DFS (both P<0.001). CONCLUSIONS/SIGNIFICANCE: LAPTM4B allele *2 is a risk
      factor associated with poor prognosis in patients with resected GBC, and LAPTM4B
      status may be therefore be useful preoperatively as an adjunct in evaluation of
      the operability of GBC.

PMID- 22984633
TI  - Measuring Intrusive Prospective Imagery using the Impact of Future Events Scale
      (IFES): Psychometric properties and relation to risk for Bipolar Disorder.
AB  - We define intrusive prospective imagery as the experience of mental imagery of
      events that may happen in the future and which come to mind involuntarily. This
      everyday phenomenon may be exacerbated in psychological disorders such as bipolar
      disorder (Holmes, Geddes, Colom, & Goodwin, 2008) although specific measures to
      assess this have been lacking. We recently developed the Impact of Future Events
      Scale (IFES; Deeprose & Holmes, 2010), which is further examined in the current
      paper. In Study 1, adults volunteers (N=50) completed the IFES on two occasions,
      with 1-week between measurements. This revealed acceptable test-rest reliability.
      In Study 2, (N=90) IFES showed good internal consistency and confirmed two
      predictions. First, in the total sample risk for bipolar disorder (MDQ;
      Hirschfield et al., 2000) and IFES Total Score correlated positively. Second,
      when the sample was split into high (MDQ >= 7) and low (MDQ <= 6) bipolarity risk
      groups, higher IFES Total Scores were observed in the high risk group. We
      conclude that 1) IFES presents a useful measure for assessing intrusive
      prospective imagery with acceptable test-retest reliability and good internal
      consistency and 2) risk for bipolar disorder is associated with elevated IFES
      Total Scores with potentially important clinical implications.

PMID- 22984634
TI  - Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of
      Achiral Profen Probes.
AB  - Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2
      arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently
      reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not
      arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of
      five profen scaffolds and evaluated them for substrate-selective inhibition using
      in vitro and cellular assays. The size of the substituents dictated the
      inhibitory strength of the analogs, with smaller substituents enabling greater
      potency but less selectivity. Inhibitors based on the flurbiprofen scaffold
      possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a)
      exhibiting an IC(50) of 0.11 MUM for inhibition of 2-AG oxygenation. The crystal
      structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar
      binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in
      mice comparable to that of ibuprofen. The data presented suggest that achiral
      profens can act as lead molecules toward in vivo probes of substrate-selective
      COX-2 inhibition.

PMID- 22984635
TI  - Drug Repurposing for Cancer Therapy.

PMID- 22984636
TI  - On the Mechanisms of Cyanine Fluorophore Photostabilization.
AB  - Cyanine fluorophores exhibit greatly improved photostability when covalently
      linked to stabilizers, such as cyclooctatetraene (COT), nitrobenzyl alcohol (NBA)
      or Trolox. However, the mechanism by which photostabilization is mediated has yet
      to be determined. Here we present spectroscopic evidence that COT, when
      covalently linked to Cy5, substantially reduces the lifetime of the Cy5 triplet
      state, and that the degree of triplet state quenching correlates with
      enhancements in photostability observed in single-molecule fluorescence
      measurements. By contrast, NBA and Trolox did not quench the Cy5 triplet state
      under our conditions suggesting that their mechanism of photostabilization is
      different from COT and does not target the fluorophore triplet state directly.
      These findings provide insights into the mechanisms of fluorophore
      photostabilization that may lead to improved fluorophore designs for biological
      imaging applications.

PMID- 22984637
TI  - Longitudinal developmental profile of children from low socio-economic
      circumstances in Cape Town, using the 1996 Griffiths Mental Development Scales.
AB  - BACKGROUND: The Griffiths Mental Development Scales (GMDS) have not been
      standardised in South African children Neurodevelopmental scores of infants from
      deprived environments decline with age, but there is no evidence on how young
      South African children from such backgrounds perform on serial assessments.  AIM:
      To describe the longitudinal developmental profile of infants from low socio
      economic backgrounds at Tygerberg Children's Hospital by comparing the GMDS
      scores performed at 10 - 12 months and 20 - 22 months.  METHODS: Infants born to
      HIV-uninfected women attending the public service programme were recruited from a
      vaccine study in Cape Town, South Africa. The GMDS 0 - 2 years and a neurological
      examination were performed between 10 and 12 months and between 20 and 22 months.
      RESULTS: Thirty-one infants (14 girls, 17 boys) were assessed. Their mean
      (standard deviation (SD)) age was 11.6 (0.8) months and 21.0 (0.5) months at the
      first and second assessments, respectively. The mean (SD) general quotient
      decreased significantly from 107.3 (11.7) to 95.0 (11.0) (p<0.001). All sub
      quotients decreased significantly except for locomotor. The hearing and language
      sub-quotient was most affected, with a decrease in mean quotients from 113.0 to
      93.2 (p<0.001). There was no evidence of intercurrent events to explain the
      decline.  INTERPRETATION: Scores on the GMDS of this group of children from low
      socio-economic backgrounds were normal at 11 months and, other than locomotor,
      decreased significantly at 21 months, with language the most affected. Further
      research is needed to determine the specific reasons for the decline.

PMID- 22984638
TI  - Dysfunctional affect regulation in borderline personality disorder and in
      somatoform disorder.
AB  - BACKGROUND: Although affect dysregulation is considered a core component of
      borderline personality disorder (BPD) and somatoform disorders (SoD), remarkably
      little research has focused on the prevalence and nature of affect dysregulation
      in these disorders. Also, despite apparent similarities, little is known about
      how dysfunctional under- and overregulation of affect and positive and negative
      somatoform and psychoform dissociative experiences inter-relate. Prior studies
      suggest a clear relationship between early childhood psychological trauma and
      affect dysregulation, especially when the caretaker is emotionally, sexually, or
      physically abusing the child, but how these relate to under- and overregulation
      while differentiating for developmental epochs is not clear. Although an elevated
      risk of childhood trauma exposure or complex posttraumatic stress disorder
      (CPTSD) symptoms has been reported in BPD and SoD, trauma histories,
      dysfunctional affect regulation, dissociation, PTSD, and CPTSD were never
      assessed in unison in BPD and/or SoD. METHOD: BPD and/or SoD diagnoses were
      confirmed or ruled out in 472 psychiatric inpatients using clinical interviews.
      Dysfunctional under- and overregulation of affect and somatoform and psychoform
      dissociation, childhood trauma-by-primary-caretaker (TPC), PTSD, and CPTSD were
      all measured using self reports. RESULTS: No disorder-specific form of
      dysfunctional affect regulation was found. Although both BPD and SoD can involve
      affect dysregulation and dissociation, there is a wide range of intensity of
      dysfunctional regulation phenomena in patients with these diagnoses. Evidence was
      found for the existence of three qualitatively different forms of experiencing
      states: inhibitory experiencing states (overregulation of affect and negative
      psychoform dissociation) most commonly found in SoD, excitatory experiencing
      states (underregulation of affect and positive psychoform dissociation) most
      commonly found in BPD, and combination of inhibitory and excitatory experiencing
      states commonly occurring in comorbid BPD+SoD. Almost two-thirds of participants
      reported having experienced childhood TPC. Underregulation of affect was
      associated with emotional TPC and TPC occurring in developmental epoch, 0-6 years
      of age. Overregulation of affect was associated with physical TPC. Almost a
      quarter of all participants met the criteria for CPTSD. BPD+SoD patients had the
      most extensive childhood trauma histories and were most likely to meet CPTSD
      criteria, followed by BPD, psychiatric comparison (PC), and SoD. The BPD+SoD and
      BPD reported significantly higher levels of CPTSD than the SoD or PC groups but
      did not differ from each other except for greater severity of CPTSD somatic
      symptoms by the BPD+SoD group. CONCLUSION: THREE QUALITATIVELY DIFFERENT FORMS OF
      DYSFUNCTIONAL REGULATION WERE IDENTIFIED: inhibitory, excitatory, and combined
      inhibitory and excitatory states. Distinguishing inhibitory versus excitatory
      states of experiencing may help to clarify differences in dissociation and affect
      dysregulation between and within BPD and SoD patients. Specific interventions
      addressing overregulation in BPD, or underregulation in SoD, should be added to
      disorder-specific evidence-based treatments. CPT is particularly prevalent in BPD
      and BPD+SoD and is differentially associated with under- and overregulation of
      affect depending on the type of traumatic exposure. CPTSD warrants further
      investigation as a potential independent syndrome or as a marker identifying a
      sub-group of affectively, or both affectively and somatically, dysregulated
      patients diagnosed with BPD who have childhood trauma histories.

PMID- 22984640
TI  - Crossed Intermolecular [2+2] Cycloaddition of Styrenes by Visible Light
      Photocatalysis.
AB  - We report a method for the crossed [2+2] cycloaddition of styrenes using visible
      light photocatalysis. Few methods for the synthesis of unsymmetrically
      substituted cyclobutanes by photochemical [2+2] cycloaddition are known. We show
      that careful tuning of the electrochemical properties of a ruthenium
      photocatalyst enable the efficient crossed [2+2] cycloaddition of styrenes upon
      irradiation with visible light. We outline the logic that enables high crossed
      chemoselectivity, and we also demonstrate that this reaction is remarkably
      efficient; gram-scale reactions can be conducted with as little as 0.025 mol% of
      the photocatalyst.

PMID- 22984642
TI  - The Creation of a Contagious H5N1 Influenza Virus: Implications for the Education
      of Life Scientists.
AB  - The paper contends that the ongoing controversy surrounding the creation of a
      contagious H5N1 influenza virus has already exposed the severe limitations of the
      possibility of preventing the hostile misuse of the life sciences by dint of
      oversight of proposals and publications. It further argues that in order to
      prevent the potential wholesale militarisation of the life sciences, it is
      essential that life scientists become aware of their responsibilities within the
      context of the Biological and Toxin Weapons Convention (BTWC) and actively
      contribute their expertise to strengthening the biological weapons non
      proliferation regime .

PMID- 22984641
TI  - Feeder-free derivation of human induced pluripotent stem cells with messenger
      RNA.
AB  - The therapeutic promise of induced pluripotent stem cells (iPSCs) has spurred
      efforts to circumvent genome alteration when reprogramming somatic cells to
      pluripotency. Approaches based on episomal DNA, Sendai virus, and messenger RNA
      (mRNA) can generate "footprint-free" iPSCs with efficiencies equaling or
      surpassing those attained with integrating viral vectors. The mRNA method
      uniquely affords unprecedented control over reprogramming factor (RF) expression
      while obviating a cleanup phase to purge residual traces of vector. Currently,
      mRNA-based reprogramming is relatively laborious due to the need to transfect
      daily for ~2 weeks to induce pluripotency, and requires the use of feeder cells
      that add complexity and variability to the procedure while introducing a route
      for contamination with non-human-derived biological material. We accelerated the
      mRNA reprogramming process through stepwise optimization of the RF cocktail and
      leveraged these kinetic gains to establish a feeder-free, xeno-free protocol
      which slashes the time, cost and effort involved in iPSC derivation.

PMID- 22984643
TI  - Disaster Metrics: A Proposed Quantitative Assessment Tool in Complex Humanitarian
      Emergencies - The Public Health Impact Severity Scale (PHISS).
AB  - BACKGROUND: Complex Humanitarian Emergencies (CHE) result in rapid degradation of
      population health and quickly overwhelm indigenous health resources. Numerous
      governmental, non-governmental, national and international organizations and
      agencies are involved in the assessment of post-CHE affected populations. To
      date, there is no entirely quantitative assessment tool conceptualized to measure
      the public health impact of CHE. METHODS: Essential public health parameters in
      CHE were identified based on the Sphere Project "Minimum Standards", and scoring
      rubrics were proposed based on the prevailing evidence when applicable. RESULTS:
      12 quantitative parameters were identified, representing the four categories of
      "Minimum Standards for Disaster Response" according to the Sphere Project;
      health, shelter, food and nutrition, in addition to water and sanitation. The
      cumulative tool constitutes a quantitative scale, referred to as the Public
      Health Impact Severity Scale (PHISS), and the score on this scale ranges from a
      minimum of 0 to a maximum of 100. CONCLUSION: Quantitative measurement of the
      public health impact of CHE is germane to accurate assessment, in order to
      identify the scale and scope of the critical response required for the relief
      efforts of the affected populations. PHISS is a new conceptual metric tool,
      proposed to add an objective quantitative dimension to the post-CHE assessment
      arsenal. PHISS has not yet been validated, and studies are needed with
      prospective data collection to test its validity, feasibility and reliability.
      CITATION: Bayram JD, Kysia R, Kirsch TD. Disaster Metrics: A Proposed
      Quantitative Assessment Tool in Complex Humanitarian Emergencies - The Public
      Health Impact Severity Scale (PHISS). PLOS Currents Disasters. 2012 Aug 21. doi:
      10.1371/4f7b4bab0d1a3.

PMID- 22984644
TI  - Impact of the 2010 pakistan floods on rural and urban populations at six months.
AB  - The 2010 Pakistan flood affected 20 million people. The impact of the event and
      recovery is measured at 6 months. METHODS: Cross-sectional cluster survey of 1769
      households conducted six months post-flood in 29 most-affected districts. The
      outcome measures were physical damage, flood-related death and illness and
      changes in income, access to electricity, clean water and sanitation facilities.
      RESULTS: Households were headed by males, large and poor. The flood destroyed
      54.8% of homes and caused 86.8% households to move, with 46.9% living in an IDP
      camp. Lack of electricity increased from 18.8% to 32.9% (p = 0.000), lack of
      toilet facilities from 29.0% to 40.4% (p=0.000). Access to protected water
      remained unchanged (96.8%); however, the sources changed (p=0.000). 88.0%
      reported loss of income (90.0% rural, 75.0% urban, p=0.000) with rural households
      loosing significantly more and less likely to recovered. Immediate deaths and
      injuries were uncommon but 77.0% reported flood-related illnesses. Significant
      differences were noted between urban and rural as well as gender and education of
      the head of houshold. DISCUSSION: After 6 months, much of the population had not
      recovered their prior standard of living or access to services. Rural households
      were more commonly impacted and slower to recover. Targeting relief to high-risk
      populations including rural, female-headed and those with lower education is
      needed. CITATION: Kirsch TD, Wadhwani C, Sauer L, Doocy S, Catlett C. Impact of
      the 2010 Pakistan Floods on Rural and Urban Populations at Six Months. PLOS
      Currents Disasters. 2012 Aug 22. doi: 10.1371/4fdfb212d2432.

PMID- 22984645
TI  - Evaluating the New York City Emergency Department Syndromic Surveillance for
      Monitoring Influenza Activity during the 2009-10 Influenza Season.
AB  - OBJECTIVE: To use laboratory data to assess the specificity of syndromes used by
      the New York City emergency department (ED) syndromic surveillance system to
      monitor influenza activity. DESIGN: For the period from October 1, 2009 through
      March 31, 2010, we examined the correlation between citywide ED syndrome
      assignment and laboratory-confirmed influenza and respiratory syncytial virus
      (RSV). In addition, ED syndromic data from five select NYC hospitals were matched
      at the patient and visit level to corresponding laboratory reports of influenza
      and RSV. The matched dataset was used to evaluate syndrome assignment by disease
      and to calculate the sensitivity and specificity of the influenza-like illness
      (ILI) syndrome. RESULTS: Citywide ED visits for ILI correlated well with
      influenza laboratory diagnoses (R=0.92). From October 1, 2009, through March 31,
      2010, there were 264,532 ED visits at the five select hospitals, from which the
      NYC Department of Health and Mental Hygiene (DOHMH) received confirmatory
      laboratory reports of 655 unique cases of influenza and 1348 cases of RSV. The ED
      visit of most (56%) influenza cases had been categorized in the fever/flu
      syndrome; only 15% were labeled ILI. Compared to other influenza-related
      syndromes, ILI had the lowest sensitivity (15%) but the highest specificity (90%)
      for laboratory-confirmed influenza. Sensitivity and specificity varied by age
      group and influenza activity level. CONCLUSIONS: The ILI syndrome in the NYC ED
      syndromic surveillance system served as a specific but not sensitive indicator
      for influenza during the 2009-2010 influenza season. Despite its limited
      sensitivity, the ILI syndrome can be more informative for tracking influenza
      trends than the fever/flu or respiratory syndromes because it is less likely to
      capture cases of other respiratory viruses. However, ED ILI among specific age
      groups should be interpreted alongside laboratory surveillance data. ILI remains
      a valuable tool for monitoring influenza activity and trends as it facilitates
      comparisons nationally and across jurisdictions and is easily communicated to the
      public.

PMID- 22984646
TI  - Maternal Body Composition and Its Relationship to Infant Breast Milk Intake in
      Rural Pakistan.
AB  - Some women in rural Pakistan are chronically undernourished, and consequently
      underweight. Concerns have been expressed that the degree of undernourishment
      might be sufficiently severe to affect lactation performance. We have obtained
      data on maternal body composition and infant breast milk intake using stable
      isotope methods in a group of thirty three mother and infant pairs at
      approximately six months of age. The maternal body mass index ranged from 16.6 to
      29.1 kg.m(-2). In this population we found that exclusive breast-feeding tended
      to be associated with lower maternal body fat, and that there was no evidence for
      compromised lactational performance due to malnourishment. Finally we note that
      when our data is combined with that from other studies there may be a generalised
      negative correlation between breast milk intake and maternal body fat.

PMID- 22984647
TI  - Extrapyramidal examinations in psychiatry.
AB  - Extrapyramidal signs include increased motor tone, changes in the amount and
      velocity of movement, and involuntary motor activity. They include two groups of
      signs and related disorders: hypokinetic (similar to Parkinson's disease) and
      hyperkinetic (similar to Huntington's disease). This article covers some of the
      neuroscience behind extrapyramidal disorders, the relevance of extrapyramidal
      signs in the major psychiatric disorders, the major extrapyramidal movement
      disorders, and how to elicit extrapyramidal signs.

PMID- 22984648
TI  - Comparison of the peak-to-trough fluctuation in plasma concentration of long
      acting injectable antipsychotics and their oral equivalents.
AB  - BACKGROUND: Small peak-to-trough drug levels have been suggested to be related to
      improved tolerability. The aim of this study is to review the steady-state, peak
      to-trough, plasma-concentration fluctuation of long-acting injectable
      antipsychotics and equivalent oral formulations. METHODS: A review of published
      literature and clinical study reports identified references that reported,
      depicted, or permitted derivation of the steady-state, peak-to-trough, plasma
      concentration fluctuation of antipsychotics (the ratio of maximum concentration
      to minimum concentration following administration according to the recommended
      dosing interval) over the dosing interval. Suitable references were identified
      for haloperidol decanoate, olanzapine pamoate, paliperidone palmitate,
      risperidone long-acting injectable, and zuclopenthixol decanoate and their oral
      equivalents except zuclopenthixol. The single-dose time to maximum plasma
      concentration (T(max)) and half-life (t(1/2)) were also identified. RESULTS: The
      steady-state, peak-to-trough, plasma-concentration ratios of oral antipsychotics
      varied from 1.47 (paliperidone extended-release, once daily) to 3.30 (active
      moiety risperidone, once daily). Among long-acting injectable antipsychotics, the
      ratios varied from 1.56 (paliperidone palmitate, once monthly) to approximately 4
      (olanzapine pamoate, once every four weeks). Among drugs with similar dosing
      intervals, longer T(max) and/or t(1/2) generally correlated with less peak-to
      trough fluctuation. CONCLUSION: Peak-to-trough fluctuations in plasma
      concentrations vary widely and may be affected by differences in dosing,
      pharmacokinetic sampling, subjects' phenotypes, concomitant medications, comorbid
      diseases, and formulation. These fluctuations may affect clinical response and
      tolerability. Along with other patient-specific and drug-specific factors, these
      fluctuations warrant consideration when selecting an antipsychotic and
      antipsychotic formulation. Further study is needed with more robust and
      generalizable peak-to-trough fluctuation data.

PMID- 22984649
TI  - A urinalysis-based comparative study of treatment adherence on buprenorphine and
      buprenorphine/naloxone combination used as opioid substitution therapy.
AB  - OBJECTIVE: The objective of the current study was to explore the difference in
      treatment adherence to directly supervised buprenorphine and take-home
      buprenorphine/ naloxone combination for opioid substitution therapy. Urinalysis
      findings have been used to check treatment adherence on opioid substitution
      therapy agent. Additionally the study aimed to explore the misuse rate of
      buprenorphine/naloxone combination based on urinalysis findings. DESIGN: Cross
      sectional chart reviewSetting: Laboratory of a tertiary care drug dependence
      treatment centerParticipants: One-year laboratory urinalysis records of a
      tertiary care, drug-dependence treatment center in India were analyzed. All the
      urine samples of subjects on opioid substitution therapy with buprenorphine or
      buprenorphine/naloxone combination were included in the study. MEASUREMENTS:
      Urinalysis using thin layer chromatography for buprenorphine and naloxone. In
      between group difference for treatment adherence on buprenorphine and
      buprenorphine/ naloxone combination was done using Mantel-Haenszel test. RESULTS:
      A higher proportion of samples from subjects on buprenorphine/naloxone tested
      positive for buprenorphine as compared to subjects on buprenorphine. Twelve
      (7.6%) urine samples from patients on buprenorphine/naloxone tested positive for
      naloxone. CONCLUSIONS: The findings of the current study suggest that
      buprenorphine/naloxone combination has a higher adherence rate as compared to
      buprenorphine when used for opioid substitution therapy.

PMID- 22984650
TI  - Prediction and prevention of aggression and seclusion by early screening and
      comprehensive seclusion documentation.
AB  - OBJECTIVE: Identification and skilled management of aggressive patients are a
      continued safety concern for inpatient psychiatric settings. We studied
      aggression reduction and the use of seclusion and restraints on our inpatient
      unit by developing aggression management tools. Our objectives were to
      systematically identify potential aggressors among admitted patients within 24 to
      48 hours of admission and develop a seclusion documentation form that
      simultaneously trains staff to use less restrictive interventions while
      collecting data on its use. METHODS: Prior to patient assessment and data
      collection, we systematically trained all medical staff on interviewing patients
      using the Phipps Aggression Screening Tool. We prospectively screened 229
      consecutive admissions using the Phipps Aggression Screening Tool and determined
      its inter-rater reliability and predictive validity. We systematically recorded
      the use of a variety of interventions, including seclusion, when applicable. We
      also documented details of acts of aggression on a comprehensive form and
      collected demographics, casemix severity, and outcomes. RESULTS: Twenty-two
      acutely ill patients were responsible for 68 violent acts, all identified by the
      Phipps Aggression Screening Tool. There were highly significant differences
      between aggressive and nonaggressive groups for length-ofstay, cost of
      hospitalization, and illness complexity. With the use of the new form, seclusion
      decreased from 32 percent to 22.4 percent in 2007. Our current use of seclusion
      is 0.1/1000 patient hours in 2011. CONCLUSION: The seclusion documentation form
      appropriately guides aggression management with less restrictive alternatives to
      seclusion, once potentially aggressive patients have been identified by
      screening.

PMID- 22984651
TI  - Dementia with lewy bodies in meige syndrome.
AB  - Meige syndrome is a rare form of segmental dystonia characterized by
      blepharospasm and oromandibular dystonia. A few case reports of Meige syndrome
      have been associated with Lewy body pathologies, and the syndrome was also
      proposed for inclusion in the spectrum of Lewy body disease. We report a case of
      an elderly gentleman with a history of Meige syndrome for more than 10 years who
      developed dementia with Lewy bodies. Updated clinical and pathological evidence
      of linkages between these two conditions is also presented.

PMID- 22984653
TI  - Educating the public through the courtroom: efforts of a forensic psychologist.

PMID- 22984652
TI  - SSRIs: bad to the bone?
AB  - Selective serotonin reuptake inhibitors are globally popular antidepressants with
      broad clinical indications. Despite an overall favorable side-effect profile, our
      examination of 19 studies, one review, and one meta-analysis indicates that these
      unique antidepressants appear to have negative effects on bone, particularly with
      regard to bone mineral density and fracture risk. These risks may be enhanced by
      more serotonergic agents and/or longer exposure to selective serotonin reuptake
      inhibitors. The magnitude of this relationship is difficult to determine due to
      the myriad of potential confounds in available studies, but all indicate risk. In
      additional support of these findings, serotonin receptors have been identified on
      osteoclasts, osteoblasts, and osteocyte cell lines, suggesting that serotonin may
      be an important regulatory agent in bone. While no formal recommendations
      regarding the use of selective serotonin reuptake inhibitors in risk populations
      are available, caution is advised in individuals with potential risk (i.e., those
      with osteoporosis or histories of osteoporotic fractures).

PMID- 22984654
TI  - Beta-amyloid toxicity modifier genes and the risk of Alzheimer's disease.
AB  - Late-onset Alzheimer's disease (LOAD) is a complex and multifactorial disease. So
      far ten loci have been identified for LOAD, including APOE, PICALM, CLU, BIN1,
      CD2AP, CR1, CD33, EPHA1, ABCA7, and MS4A4A/MS4A6E, but they explain about 50% of
      the genetic risk and thus additional risk genes need to be identified. Amyloid
      beta (Abeta) plaques develop in the brains of LOAD patients and are considered to
      be a pathological hallmark of this disease. Recently 12 new Abeta toxicity
      modifier genes (ADSSL1, PICALM, SH3KBP1, XRN1, SNX8, PPP2R5C, FBXL2, MAP2K4,
      SYNJ1, RABGEF1, POMT2, and XPO1) have been identified that potentially play a
      role in LOAD risk. In this study, we have examined the association of 222 SNPs in
      these 12 candidate genes with LOAD risk in 1291 LOAD cases and 958 cognitively
      normal controls. Single site and haplotype analyses were performed using PLINK.
      Following adjustment for APOE genotype, age, sex, and principal components, we
      found single nucleotide polymorphisms (SNPs) in PPP2R5C, PICALM, SH3KBP1, XRN1,
      and SNX8 that showed significant association with risk of LOAD. The top SNP was
      located in intron 3 of PPP2R5C (P=0.009017), followed by an intron 19 SNP in
      PICALM (P=0.0102). Haplotype analysis revealed significant associations in
      ADSSL1, PICALM, PPP2R5C, SNX8, and SH3KBP1 genes. Our data indicate that genetic
      variation in these new candidate genes affects the risk of LOAD. Further
      investigation of these genes, including additional replication in other case
      control samples and functional studies to elucidate the pathways by which they
      affect Abeta, are necessary to determine the degree of involvement these genes
      have for LOAD risk.

PMID- 22984656
TI  - Letter from the editors.

PMID- 22984655
TI  - Physical Activity Effects on Depressive Symptoms in Black Adults.
AB  - OBJECTIVES: Randomized trials found physical activity (PA) effective in
      decreasing depressive symptoms. Few studies included Black participants. The
      purpose of this systematic literature review was to determine the effects of PA
      on depressive symptoms in Black adults.  METHODS: Articles were abstracted by
      conducting a computer and hand search of eligible studies.  RESULTS: Eight of 13
      studies found a significant inverse relationship between PA and depressive
      symptoms in Black adults. Sources for the heterogeneity were explored. 
      CONCLUSION: Future studies should include representative samples of Black adults,
      incorporate a theory which considers multiple levels of influence, account for
      genetic factors in the etiology of depressive symptoms, include individuals
      diagnosed with depression and with health conditions which may increase the risk
      of depressive symptoms, account for intra-group ethnic heterogeneity, measure and
      differentiate between social support and social network, consider aspects of the
      physical environment and use standardized measurements of PA.

PMID- 22984657
TI  - Radiofrequency waves with filling and peeling substances: An innovative minimally
      invasive technique for facial rejuvenation.
AB  - INTRODUCTION: This study describes a pivotal clinical trial of a new minimally
      invasive cosmetic procedure for facial rejuvenation and for the treatment of
      scars and wrinkles. METHODS: The procedure consisted of a combination of
      techniques such as fillers, biorevitalization, peeling, and intradermal
      radiofrequency, emitted from a new device denominated by Spherofill Medical Plus
      (SMP; Spherofill MD, PromoItalia Group S.p.A., Pozzuoli, Italy), for treating
      cutaneous regeneration, depressions, and striae. One hundred and twelve patients,
      divided into five groups, were treated. RESULTS: The results produced were
      statistically analyzed and resulted in significant and long-lasting effects for
      facial rejuvenation. Indeed, the analysis of the Global Aesthetic Improvement
      Scale (GAIS) scores in the five groups demonstrated statistically significant
      results between 3 and 9 months after the treatments. CONCLUSION: Evaluating the
      patients included in the study, it is possible to conclude that the treatment
      with SMP represents a safe and efficient solution for the treatment of wrinkles,
      acne lesions, striae, and of degenerated tissues caused by aging.

PMID- 22984658
TI  - Circumscribed palmar hypokeratosis: Successful treatment with fluorouracil cream.
AB  - INTRODUCTION: The pathogenesis of circumscribed palmar hypokeratosis (CPH) is
      still controversial, and to date there is no treatment of choice. METHODS: We
      report on a patient with CPH responding to treatment with fluorouracil cream.
      RESULTS: The clinical course and histopathological features in our observation
      point towards the possibility of an underlying squamous cell carcinoma in situ
      presenting as CPH. CONCLUSION: We suggest that fluorouracil cream treatment
      should be considered as a therapeutic option in cases of CPH.

PMID- 22984659
TI  - Late-onset disseminated superficial actinic porokeratosis in an elderly woman.
AB  - INTRODUCTION: Disseminated superficial actinic porokeratosis (DSAP) is the most
      common form of porokeratosis. A case of late-onset DSAP is reported with an
      uncommon presentation in an elderly patient. METHODS: An 80-year-old woman, with
      diabetes mellitus treated with metformin, and hypertension treated with
      metoprolol and captopril, presented with multiple 2 mm-to-7 cm brown patches, for
      5 years. The patches were often confluent with an atrophic center and a well
      demarcated keratotic border located on the thighs, lower legs, and feet. RESULTS:
      Histological examination of a cutaneous biopsy showed the presence of rare
      cornoid lamellae, confirming the clinical diagnosis of DSAP. CONCLUSION: In this
      report, the atypical presentation of DSAP is discussed in this elderly patient
      and also the possible triggering factors at this age.

PMID- 22984660
TI  - Erosive lichen planus of the soles: Effective response to prednisone.
AB  - BACKGROUND: Erosive lichen planus (LP) of the soles is a rare variant of LP,
      characterized by chronic, painful, and disabling plantar ulcerations. Herein, we
      report a case with complete healing following treatment with systemic steroids.
      CASE REPORT: A 38-year-old woman was referred with painful and disabling erosive
      bilateral plantar LP, which she had experienced for 6 weeks. A 1 mg/kg/day, oral
      prednisone therapy led to rapid improvement and complete healing within 3 weeks,
      with a sustained result under a low dose maintenance therapy. DISCUSSION:
      Ulcerative plantar LP is significantly known to be unresponsive to several
      topical and systemic therapies. Surgical excision and grafting is the treatment
      of choice. Systemic steroids are reported to have inefficient or partial results;
      both on cutaneous healing and on maintenance of the result. Our patient achieved
      complete cicatrisation with a sustained result of 3 months under a low dose of
      prednisone (5 mg/day).

PMID- 22984661
TI  - Nevus lipomatosus cutaneous superficialis: Report of eight cases.
AB  - INTRODUCTION: Nevus lipomatosus cutaneous superficialis (NLCS) is a rare benign
      hamartomatous skin tumor characterized by dermal deposition of mature adipose
      tissue. It's classified in two types: the classical form with multiple soft,
      pedunculated, cerebriform papules and nodules that coalesce into plaques, and the
      solitary form that consists of a solitary papule or nodule. In this study, eight
      cases of NLCS are reported. METHODS: The study was a retrospective case series
      including all patients with histopathologically documented NLCS who attended the
      Dermatology Department of Charles Nicolle hospital between January 1997 and
      December 2010. The objective of our study was to determine the epidemioclinical
      characteristics, the histopathologic features, and the treatment of this
      hamartoma. Patients included three males and five females aged between 7 and 41
      years. RESULTS: In four cases hamartoma was present since childhood, and in the
      other four cases it appeared in the third and fourth decades. Classical form was
      noted in seven cases and the solitary form in one case. Lesions involved limbs in
      four patients and trunk in four patients. Seven patients underwent surgical
      excision, and for one case no treatment was proposed. CONCLUSION: The multiple or
      classical form is largely predominant in our study. Habitually, NLCS has an
      asymptomatic course. Treatment is usually not necessary unless for cosmetic
      reasons; surgical excision is curative and recurrence after is rare.

PMID- 22984662
TI  - Bullous Darier's disease mimicking Hailey-Hailey disease.
AB  - BACKGROUND: The bullous variant of Darier's disease (DD) is a rare type
      characterized by histological and clinical overlap with Hailey-Hailey disease
      (HDD). CASE REPORTS: The following case report describes two cases of familial
      DD; a 51-year-old woman who presented with erythematous plaques, covered by small
      blisters in axillary and inguinal areas, and the first patient's daughter, who
      presented with keratotic papules localized on the axillary and inframammary
      folds. CONCLUSION: These two cases are original by the predominant flexural
      distribution, and by a bullous form in the first case, clinically and
      histologically mimicking HHD.

PMID- 22984663
TI  - Lupoid cutaneous leishmaniasis: a case report.
AB  - BACKGROUND: Lupoid cutaneous leishmaniasis (CL) is a rare form of CL having a
      striking resemblance to other granulomatous cutaneous conditions of infectious or
      inflammatory origin. The authors present a patient with a facial lupoid CL and
      discuss the diagnostic tools of this parasitological infection, the main
      differential diagnosis, and treatment. CASE REPORT: A 54-year-old Tunisian woman,
      with no past medical history of lupus erythematosus or infectious disease,
      presented with a 3-month history of a slowly enlarging erythematous and
      infiltrated plaque, extending over the nose, the right cheek, and the internal
      aspect of the right lower eyelid. Microscopic examination of a parasitological
      smear showed numerous leishmania in their amastigote form, inside monocytes,
      confirming the diagnosis of CL. Clinical aspect was in favor of lupoid CL. The
      patient was cured by fluconazole 200 mg/day for 6 weeks after pancreatic
      intolerance with intramuscular meglumine antimoniate (60 mg/kg/day for 7 days),
      and no response to doxycycline (200 mg/day for 6 weeks). DISCUSSION: Lupoid CL is
      easily suspected in countries in which there is an endemic of leishmaniasis. In
      countries where there isn't an endemic, although rarely observed, this diagnosis
      should also be kept in mind in front of an infiltrated facial lesion of a
      tuberculoid aspect on histology, especially when there is a positive travel
      history to an area in which there is an endemic.

PMID- 22984664
TI  - Basics of particle therapy I: physics.
AB  - With the advance of modern radiation therapy technique, radiation dose
      conformation and dose distribution have improved dramatically. However, the
      progress does not completely fulfill the goal of cancer treatment such as
      improved local control or survival. The discordances with the clinical results
      are from the biophysical nature of photon, which is the main source of radiation
      therapy in current field, with the lower linear energy transfer to the target. As
      part of a natural progression, there recently has been a resurgence of interest
      in particle therapy, specifically using heavy charged particles, because these
      kinds of radiations serve theoretical advantages in both biological and physical
      aspects. The Korean government is to set up a heavy charged particle facility in
      Korea Institute of Radiological & Medical Sciences. This review introduces some
      of the elementary physics of the various particles for the sake of Korean
      radiation oncologists' interest.

PMID- 22984665
TI  - Radiation-induced brain injury: retrospective analysis of twelve pathologically
      proven cases.
AB  - PURPOSE: This study was designed to determine the influencing factors and
      clinical course of pathologically proven cases of radiation-induced brain injury
      (RIBI). MATERIALS AND METHODS: The pathologic records of twelve patients were
      reviewed; these patients underwent surgery following radiotherapy due to disease
      progression found by follow-up imaging. However, they were finally diagnosed with
      RIBI. All patients had been treated with 3-dimensional conventional fractionated
      radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or
      without chemotherapy. The histological distribution was as follows: two falx
      meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma,
      one low grade oligodendroglioma, and one small cell lung cancer with brain
      metastasis. RESULTS: Radiation necrosis was noted in eight patients and the
      remaining four were diagnosed with radiation change. Gender (p = 0.061) and
      biologically equivalent dose (BED)(3) (p = 0.084) were the only marginally
      influencing factors of radiation necrosis. Median time to RIBI was 7.3 months
      (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In
      the subgroup analysis of high grade gliomas, RIBI that developed <6 months after
      radiotherapy was associated with inferior overall survival rates compared to
      cases of RIBI that occurred >=6 months (p = 0.085). CONCLUSION: Our study
      demonstrated that RIBI could occur in early periods after conventional
      fractionated brain radiotherapy within normal tolerable dose ranges. Studies with
      a larger number of patients are required to identify the strong influencing
      factors for RIBI development.

PMID- 22984666
TI  - Radiotherapy for pituitary adenomas: long-term outcome and complications.
AB  - PURPOSE: To evaluate long-term local control rate and toxicity in patients
      treated with external beam radiotherapy (EBRT) for pituitary adenomas. MATERIALS
      AND METHODS: We retrospectively reviewed the medical records of 60 patients
      treated with EBRT for pituitary adenoma at Korea University Medical Center from
      1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had
      non-secreting tumors. Fifty-seven patients had received postoperative
      radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy
      (range, 36 to 61.2 Gy). The definition of tumor progression were as follows:
      evidence of tumor progression on computed tomography or magnetic resonance
      imaging, worsening of clinical sign requiring additional operation or others,
      rising serum hormone level against a previously stable or falling value, and
      failure of controlling serum hormone level so that the hormone level had been far
      from optimal range until last follow-up. Age, sex, hormone secretion, tumor
      extension, tumor size, and radiation dose were analyzed for prognostic
      significance in tumor control. RESULTS: Median follow-up was 5.7 years (range, 2
      to 14.4 years). The 10-year actuarial local control rates for non-secreting and
      secreting adenomas were 96% and 66%, respectively. In univariate analysis,
      hormone secretion was significant prognostic factor (p = 0.042) and cavernous
      sinus extension was marginally significant factor (p = 0.054) for adverse local
      control. All other factors were not significant. In multivariate analysis,
      hormone secretion and gender were significant. Fifty-three patients had mass
      effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss
      of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with
      headache and 27 of 34 patients with visual impairment were improved. Twenty-seven
      patients experienced symptoms of endocrine hypersecretion (galactorrhea,
      amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly,
      and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea
      in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4
      patients. Long-term complication was observed in 4 patients; 3 patients with
      cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4
      received more than 60 Gy of irradiation. CONCLUSION: EBRT is highly effective in
      preventing recurrence and reducing mass effect of non-secreting adenoma. Effort
      to improve tumor control of secreting adenoma is required. Careful long-term
      follow-up is required when relatively high dose is applied. Modern radiosurgery
      or proton RT may be options to decrease late complications.

PMID- 22984667
TI  - Co-authorship patterns and networks of Korean radiation oncologists.
AB  - PURPOSE: This research aimed to analyze the patterns of co-authorship network
      among the Korean radiation oncologists and to identify attributing factors for
      the formation of networks. MATERIALS AND METHODS: A total of 1,447 articles
      including contents of 'Radiation Oncology' and 'Therapeutic Radiology' were
      searched from the KoreaMed database. The co-authorship was assorted by the
      author's full name, affiliation and specialties. UCINET 6.0 was used to figure
      out the author's network centrality and the cluster analysis, and KeyPlayer 1.44
      program was used to get a result of key player index. Sociogram was analyzed with
      the Netdraw 2.090. The statistical comparison was performed by a t-test and ANOVA
      using SPSS 16.0 with p-value < 0.05 as the significant value. RESULTS: The number
      of articles written by a radiation oncologist as the first author was 1,025 out
      of 1,447. The pattern of co-authorship was classified into five groups. For
      articles of which the first author was a radiation oncologist, the number of
      single-author articles (type-A) was 81; single-institution articles (type-B) was
      687; and multiple-author articles (type-C) was 257. For the articles which
      radiation oncologists participated in as a co-author, the number of single
      institution articles (type-D) was 280 while multiple-institution articles (type
      E) were 142. There were 8,895 authors from 1,366 co-authored articles, thus the
      average number of authors per article was 6.51. It was 5.73 for type-B, 6.44 for
      type-C, 7.90 for type-D, and 7.67 for type-E (p = 0.000) in the average number of
      authors per article. The number of authors for articles from the hospitals
      published more than 100 articles was 7.23 while form others was 5.94 (p = 0.005).
      Its number was 5.94 and 7.16 for the articles published before and after 2001 (p
      = 0.000). The articles written by a radiation oncologist as the first author had
      5.92 authors while others for 7.82 (p = 0.025). Its number was 5.57 and 7.71 for
      the Journal of the Korean Society for Therapeutic Radiology and Oncology and
      others (p = 0.000), respectively. Among the analysis, a significant difference in
      the average number of author per article was indicated. The out-degree centrality
      of network among authors was 4.26% (2.03.7.09%) while in-degree centrality was
      1.31% (0.53.2.84%). The three significant nodes were classified and listed as
      following: Choi, Eun Kyung for 1991-1995, Kim, Dae Young for 1998-2001, Park, Won
      and Lee, Sang Wook for 2003-2010. Choi, Eun Kyung and Kim, Dae Young appeared in
      two cases, and ranked as the highest degree in centrality. In the key player
      analysis, Choi, Eun Kyung and Lee, Sang Wook appeared in two cases, and ranked as
      the highest. From the cluster analysis, Sungkyunkwan University, Seoul National
      University and Yonsei University revealed as the three large clusters when Ulsan
      University, Chonnam National University, and Korea Institute of Radiological &
      Medical Science as the medium clusters. CONCLUSION: The Korean radiation
      oncologist's society shows a closed network with numerous relationships among the
      particular clusters, and the result indicates it is different from other
      institutions in the pattern of co-authorship formation of the major hospitals.

PMID- 22984668
TI  - Treatment outcome of nasal natural killer/T-cell lymphoma.
AB  - PURPOSE: To evaluate the radiotherapy treatment outcome of patients in stage IE
      and IIE nasal natural killer/T-cell lymphoma. MATERIALS AND METHODS: From August
      1999 to August 2009, 46 patients with stage IE and IIE nasal natural killer/T
      cell lymphoma were treated by definitive radiotherapy and chemotherapy. 33
      patients were treated with chemotherapy followed by radiotherapy (CT + RT) and
      they received 50.4 Gy in 28 fractions. 13 patients were treated with concurrent
      chemoradiotherapy (CCRT) and they received 40 Gy in 20 fractions. RESULTS: The
      median follow-up period was 4.6-137.6 months (median, 50.2 months) for all
      patients. The 4-year overall survival was 68.6% and 4-year disease free survival
      (DFS) was 61.9%. The 4-year locoregional recurrence free survival was 65.0%, and
      4-year distant metastasis free survival (DMFS) was 66.2%. For patients treated
      with CT + RT, 15 patients (45.5%) achieved complete response after chemotherapy,
      and 13 patients (39.4%) achieved partial response. 13 patients (81.8%) achieved
      complete response after radiotherapy, and 6 patients (18.2%) achieved partial
      response. For patients treated with CCRT, 11 patients (84.6%) achieved complete
      response, and one patient (7.7%) achieved partial response. In univariate
      analysis, presence of cervical lymph node metastasis was only significant
      prognostic factor for DFS and DMFS. CONCLUSION: This study did not show
      satisfactory overall survival rate and disease free survival rate of definitive
      radiotherapy and chemotherapy for stage IE and IIE nasal natural killer/T-cell
      lymphoma. For patients with cervical lymph node metastasis, further investigation
      of new chemotherapy regimens is necessary to reduce the distant metastasis.

PMID- 22984669
TI  - Factors predicting radiation pneumonitis in locally advanced non-small cell lung
      cancer.
AB  - PURPOSE: Thoracic radiotherapy is a major treatment modality of stage III non
      small cell lung cancer. The normal lung tissue is sensitive to radiation and
      radiation pneumonitis is the most important dose-limiting complication of
      thoracic radiation therapy. This study was performed to identify the clinical and
      dosimetric parameters related to the risk of radiation pneumonitis after
      definitive radiotherapy in stage III non-small cell cancer patients. MATERIALS
      AND METHODS: The medical records were reviewed for 49 patients who completed
      definitive radiation therapy for locally advanced non-small cell lung cancer from
      August 2000 to February 2010. Radiation therapy was delivered with the daily dose
      of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy
      (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy
      to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and
      forty two patients (85.7%) were treated with chemotherapy either sequentially or
      concurrently. RESULTS: Twenty-five cases (51.0%) out of 49 cases experienced
      radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%)
      were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were
      grade 4. In the univariate analyses, no clinical factors including age, sex,
      performance status, smoking history, underlying lung disease, tumor location,
      total radiation dose and chemotherapy were associated with grade >=2 radiation
      pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent
      rather than sequential chemotherapy was significantly related to grade >=2
      radiation pneumonitis comparing sequential chemotherapy. In the univariate
      analysis with dosimetric factors, mean lung dose (MLD), V(20), V(30), V(40),
      MLDipsi, V(20)ipsi, V(30)ipsi, and V(40)ipsi were associated with grade >=2
      radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30
      were independent predicting factors for grade >=2 radiation pneumonitis.
      CONCLUSION: Concurrent chemotherapy, MLD and V(30) were statistically significant
      predictors of grade >=2 radiation pneumonitis in patients with stage III non
      small cell lung cancer undergoing definitive radiotherapy. The cutoff values for
      MLD and V(30) were 16 Gy and 18%, respectively.

PMID- 22984670
TI  - The role of squamous cell carcinoma antigen as a prognostic and predictive factor
      in carcinoma of uterine cervix.
AB  - PURPOSE: Although the role of squamous cell carcinoma antigen (SCC-Ag) as a
      predictive and prognostic factor for uterine cervical cancer has been identified
      in previous studies, 1) the effective patient group of screening for recurrence
      with SCC-Ag, 2) the relationship between SCC-Ag and recurrence site, and 3) the
      relationship between the change of SCC-Ag and treatment outcome or recurrence
      have not been described. MATERIALS AND METHODS: The study included 506 patients
      with histologically proven uterine cervical cancer between January 1994 and
      December 2010. We determining the serum SCC-Ag level before treatment and after
      treatment, and conducted a retrospective review of the patients' records. We
      evaluated the sensitivity and specificity of SCC-Ag for the detection of tumor
      recurrence by comparing biochemical recurrence with clinical recurrence. RESULTS:
      The pretreatment SCC-Ag level and the proportion of patients over 1.5 ng/mL were
      higher in poor prognostic patient group. In the univariate and multivariate
      analysis, pretreatment SCC-Ag showed a statistically significant correlation with
      tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage,
      pathology. In patients with biochemical recurrence vs. those without, 5-year DFS
      and OS were 27.6 vs. 92.7% (p <= 0.001) and 53.7 vs. 92.5% (p <= 0.001),
      respectively. CONCLUSION: Our study reconfirmed the known function of
      pretreatment SCC-Ag, but could not confirm the function of biochemical response
      as a predictive factor for treatment and as a prognostic factor. There was no
      statistically significant relationship between SCC-Ag level and recurrence site.
      We confirmed the role of SCC-Ag as a follow-up tool for recurrence of disease and
      which patient groups SCC-Ag was more useful for.

PMID- 22984671
TI  - A comparison of preplan MRI and preplan CT-based prostate volume with
      intraoperative ultrasound-based prostate volume in real-time permanent
      brachytherapy.
AB  - PURPOSE: The present study compared the difference between intraoperative
      transrectal ultrasound (iTRUS)-based prostate volume and preplan computed
      tomography (CT), preplan magnetic resonance imaging (MRI)-based prostate volume
      to estimate the number of seeds needed for appropriate dose coverage in permanent
      brachytherapy for prostate cancer. MATERIALS AND METHODS: Between March 2007 and
      March 2011, among 112 patients who underwent permanent brachytherapy with (125)I,
      60 image scans of 56 patients who underwent preplan CT (pCT) or preplan MRI
      (pMRI) within 2 months before brachytherapy were retrospectively reviewed. Twenty
      four cases among 30 cases with pCT and 26 cases among 30 cases with pMRI received
      neoadjuvant hormone therapy (NHT). In 34 cases, NHT started after acquisition of
      preplan image. The median duration of NHT after preplan image acquisition was 17
      and 21 days for cases with pCT and pMRI, respectively. The prostate volume
      calculated by different modalities was compared. And retrospective planning with
      iTRUS image was performed to estimate the number of (125)I seed required to
      obtain recommended dose distribution according to prostate volume. RESULTS: The
      mean difference in prostate volume was 9.05 mL between the pCT and iTRUS and 6.84
      mL between the pMRI and iTRUS. The prostate volume was roughly overestimated by
      1.36 times with pCT and by 1.33 times with pMRI. For 34 cases which received NHT
      after image acquisition, the prostate volume was roughly overestimated by 1.45
      times with pCT and by 1.37 times with pMRI. A statistically significant
      difference was found between preplan image-based volume and iTRUS-based volume (p
      < 0.001). The median number of wasted seeds is approximately 13, when the pCT or
      pMRI volume was accepted without modification to assess the required number of
      seeds for brachytherapy. CONCLUSION: pCT-based volume and pMRI-based volume
      tended to overestimate prostate volume in comparison to iTRUS-based volume. To
      reduce wasted seeds and cost of the brachytherapy, we should take the volume
      discrepancy into account when we estimate the number of (125)I seeds for
      permanent brachytherapy.

PMID- 22984672
TI  - Analysis of changes in dose distribution due to respiration during IMRT.
AB  - PURPOSE: Intensity modulated radiation therapy (IMRT) is a high precision therapy
      technique that can achieve a conformal dose distribution on a given target.
      However, organ motion induced by respiration can result in significant dosimetric
      error. Therefore, this study explores the dosimetric error that result from
      various patterns of respiration. MATERIALS AND METHODS: Experiments were designed
      to deliver a treatment plan made for a real patient to an in-house developed
      motion phantom. The motion pattern; the amplitude and period as well as inhale
      exhale period, could be controlled by in-house developed software. Dose
      distribution was measured using EDR2 film and analysis was performed by RIT113
      software. Three respiratory patterns were generated for the purpose of this
      study; first the 'even inhale-exhale pattern', second the slightly long exhale
      pattern (0.35 seconds longer than inhale period) named 'general signal pattern',
      and third a 'long exhale pattern' (0.7 seconds longer than inhale period). One
      dimensional dose profile comparisons and gamma index analysis on 2 dimensions
      were performed RESULTS: In one-dimensional dose profile comparisons, 5% in the
      target and 30% dose difference at the boundary were observed in the long exhale
      pattern. The center of high dose region in the profile was shifted 1 mm to inhale
      (caudal) direction for the 'even inhale-exhale pattern', 2 mm and 5 mm shifts to
      exhale (cranial) direction were observed for 'slightly long exhale pattern' and
      'long exhale pattern', respectively. The areas of gamma index >1 were 11.88%,
      15.11%, and 24.33% for 'even inhale-exhale pattern', 'general pattern', and 'long
      exhale pattern', respectively. The long exhale pattern showed largest errors.
      CONCLUSION: To reduce the dosimetric error due to respiratory motions,
      controlling patient's breathing to be closer to even inhaleexhale period is
      helpful with minimizing the motion amplitude.

PMID- 22984673
TI  - Variable uterine uptake of FDG in adenomyosis during concurrent chemoradiation
      therapy for cervical cancer.
AB  - To avoid improper tumor volume contouring in radiation therapy (RT) and other
      invasive procedures, we report a case of uterine adenomyosis showing increased
      (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography
      (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman
      during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The
      adenomyosis was not associated with her menstrual cycle or with normal
      endometrium uptake, and it resolved one month after completion of RT. This case
      indicates that uterine adenomyosis in a premenopausal woman may show false
      positive uptake of (18)FDG-PET/CT associated with CCRT.

PMID- 22984674
TI  - Helical tomotherapy for spine oligometastases from gastrointestinal malignancies.
AB  - PURPOSE: This study evaluated the treatment effectiveness and proper radiation
      dose of helical tomotherapy (HT) in spine oligometastases from gastrointestinal
      cancers. MATERIALS AND METHODS: From 2006 to 2010, 20 gastrointestinal cancer
      patients were treated with HT for spine oligometastases (31 spine lesions). The
      gross tumor volume (GTV) was the tumor evident from magnetic resonance imaging
      images fused with simulation computed tomography images. Clinical target volume
      (CTV) encompassed involved vertebral bodies or dorsal elements. We assumed that
      the planning target volume was equal to the CTV. We assessed local control rate
      after HT for 31 spine metastases. Pain response was scored by using a numeric
      pain intensity scale (NPIS, from 0 to 10). RESULTS: Spine metastatic lesions were
      treated with median dose of 40 Gy (range, 24 to 51 Gy) and median 5 Gy per
      fraction (range, 2.5 to 8 Gy) to GTV with median 8 fractions (range, 3 to 20
      fraction). Median biologically equivalent dose (BED, alpha/beta = 10 Gy) was 52
      Gy(10) (range, 37.5 to 76.8 Gy(10)) to GTV. Six month local control rate for
      spine metastasis was 90.3%. Overall infield failure rate was 15% and outfield
      failure rate was 75%. Most patients showed pain relief after HT (93.8%). Median
      local recurrence free survival was 3 months. BED over 57 Gy(10) and
      oligometastases were identified as prognostic factors associated with improved
      local progression free survival (p = 0.012, p = 0.041). CONCLUSION: HT was
      capable of delivering higher BED to metastatic lesions in close proximity of the
      spinal cord. Spine metastases from gastrointestinal tumors were sensitive to high
      dose radiation, and BED (alpha/beta = 10 Gy) higher than 57 Gy(10) could improve
      local control.

PMID- 22984675
TI  - The influence of adjuvant radiotherapy on patterns of failure and survivals in
      uterine carcinosarcoma.
AB  - PURPOSE: To evaluate the impact of postoperative radiotherapy (PORT) on patterns
      of failure and survivals in uterine carcinosarcoma patients treated with radical
      surgery. MATERIALS AND METHODS: Between October 1998 and August 2010, 19 patients
      with stage I-III uterine carcinosarcoma received curative hysterectomy and
      bilateral salpingo-oophorectomy with or without PORT at Seoul National University
      Hospital. Their hospital medical records were retrospectively reviewed. PORT and
      non-PORT groups included 11 and 8 patients, respectively. They were followed for
      a mean of 22.7 months (range, 7.8 to 126.6 months). RESULTS: At 5 years, the
      overall survival rates were 51.9% for entire, 61.4% for PORT, and 41.7% for non
      PORT groups, respectively. There was no statistical difference between PORT and
      non-PORT groups with regard to overall survival (p = 0.682). Seven out of 19
      (36.8%) patients showed treatment failures, which all happened within 12 months.
      Although the predominant failures were distant metastasis in PORT group and loco
      regional recurrence in non-PORT group, there was no statistically significant
      difference in loco-regional recurrence-free survival (LRRFS) (p = 0.362) or
      distant metastasis-free survival (DMFS) (p = 0.548). Lymph node metastasis was
      found to be a significant prognostic factor in predicting poor LRRFS (p = 0.013)
      and DMFS (p = 0.021), while the International Federation Gynecology and
      Obstetrics (FIGO) stage (p = 0.043) was associated with LRRFS. CONCLUSION:
      Considering that adjuvant radiotherapy after surgical resection was effective to
      decrease loco-regional recurrence and most treatment failures were distant
      metastasis, multimodal therapy including surgery, radiotherapy, and chemotherapy
      might be an optimal treatment for uterine carcinosarcoma patients.

PMID- 22984676
TI  - Comparison of elective inguinal node irradiation techniques in anal cancer.
AB  - PURPOSE: To compare photon thunderbird with deep match (technique 1) with 3-field
      technique with electron inguinal boost (technique 2) in acute skin toxicity,
      toxicity-related treatment breaks and patterns of failure in elective inguinal
      radiation therapy (RT) for curative chemoradiation in anal cancer. MATERIALS AND
      METHODS: Seventeen patients treated between January 2008 and September 2010
      without evidence of inguinal and distant metastasis were retrospectively
      reviewed. In 9 patients with technique 1, dose to inguinal and whole pelvis area
      was 41.4 to 45 Gy and total dose was 59.4 Gy. In 8 patients with technique 2,
      doses to inguinal, whole pelvis, gross tumor were 36 to 41.4 Gy, 36 to 41.4 Gy,
      and 45 to 54 Gy, respectively. The median follow-up period was 27.6 and 14.8
      months in group technique 1 and 2, respectively. RESULTS: The incidences of grade
      3 radiation dermatitis were 56% (5 patients) and 50% (4 patients), dose ranges
      grade 3 dermatitis appeared were 41.4 to 50.4 Gy and 45 to 54 Gy in group
      technique 1 and 2, respectively (p = 0.819). The areas affected by grade 3
      dermatitis in 2 groups were as follow: perianal and perineal areas in 40% and
      25%, perianal and inguinal areas in 0% and 50%, and perianal area only in 60% and
      25%, respectively (p = 0.196). No inguinal failure has been observed. CONCLUSION:
      Photon thunderbird with deep match technique and 3-field technique with electron
      inguinal boost showed similar incidence of radiation dermatitis. However, photon
      thunderbird with deep match seems to increase the possibility of severe perineal
      dermatitis.

PMID- 22984677
TI  - FDG-PET/CT as prognostic factor and surveillance tool for postoperative radiation
      recurrence in locally advanced head and neck cancer.
AB  - PURPOSE: To evaluate the prognostic value of metabolic tumor volume (MTV) and
      maximum standardized uptake value (SUVmax) on initial positron emission
      tomography-computed tomography (PET-CT) and investigate the clinical value of
      SUVmax for early detection of locoregional recurrent disease after postoperative
      radiotherapy in patients with locally advanced head and neck squamous cell
      carcinoma (HNSCC). MATERIALS AND METHODS: A total of 100 patients with locally
      advanced HNSCC received primary tumor excision and neck dissection followed by
      adjuvant radiotherapy with or without chemotherapy. The MTV and SUVmax were
      measured from primary sites and neck nodes. The prognostic value of MTV and
      SUVmax were assessed using initial staging PET/CT (study A). Follow-up PET/CT
      scan available after postoperative concurrent chemoradiotherapy or radiotherapy
      were evaluated for the SUVmax value and correlated with locoregional recurrence
      (study B). A receiver operating characteristic (ROC) curve analysis was used to
      define a threshold value of SUVmax with the highest accuracy for recurrent
      disease assessment. RESULTS: High MTV (>41 mL) is negative prognostic factor for
      disease free survival (p = 0.041). Postradiation SUVmax was significantly
      correlated with locoregional recurrence (hazard ratio, 1.812; 95% confidence
      interval, 1.361 to 2.413; p < 0.001). A cut-off value of 5.38 from follow-up
      PET/CT was identified as having maximal accuracy for detecting locoregional
      recurrence by ROC analysis. CONCLUSION: MTV at staging work-up was significantly
      associated with disease free survival. The SUVmax value from follow-up PET/CT
      showed high diagnostic accuracy for the detection of locoregional recurrence in
      postoperatively irradiated HNSCC.

PMID- 22984678
TI  - Retrospective analysis of treatment outcomes after postoperative
      chemoradiotherapy in advanced gastric cancer.
AB  - PURPOSE: To evaluate retrospectively the survival outcome, patterns of failure,
      and complications in patients treated with postoperative chemoradiotherapy (CRT)
      in advanced gastric cancer. MATERIALS AND METHODS: Between January 2000 and
      December 2006, 80 patients with advanced gastric cancer who received
      postoperative concurrent CRT were included. Pathological staging was IB-II in 9%,
      IIIA in 38%, IIIB in 33%, and IV in 21%. Radiotherapy consisted of 45 Gy of
      radiation. Concurrent chemotherapy consisted of a continuous intravenous infusion
      of 5-fluorouracil and leucovorin on the first 4 days and last 3 days of
      radiotherapy. RESULTS: The median follow-up period was 48 months (range, 3 to 83
      months). The 5-year overall survival, disease-free survival, and locoregional
      recurrence-free survivals were 62%, 59%, and 80%, respectively. In the
      multivariate analysis, significant factors for disease-free survival were T stage
      (hazard ratio [HR], 0.278; p = 0.038), lymph node dissection extent (HR, 0.201; p
      = 0.002), and maintenance oral chemotherapy (HR, 2.964; p = 0.004). Locoregional
      recurrence and distant metastasis occurred in 5 (6%) and 18 (23%) patients,
      respectively. Mixed failure occurred in 10 (16%) patients. Grade 3 leukopenia and
      thrombocytopenia were observed in 4 (5%) and one (1%) patient, respectively.
      Grade 3 nausea and vomiting developed in 8 (10%) patients. Intestinal obstruction
      developed in one (1%). CONCLUSION: The survival outcome of the postoperative CRT
      in advanced gastric cancer was similar to those reported previously. Our
      postoperative CRT regimen seems to be a safe and effective method, reducing
      locoregional failure without severe treatment toxicity in advanced gastric cancer
      patients.

PMID- 22984679
TI  - Treatment outcome of postoperative radiotherapy for retroperitoneal sarcoma.
AB  - PURPOSE: To evaluate the treatment outcome and prognostic factor after
      postoperative radiotherapy in retroperitoneal sarcoma. MATERIALS AND METHODS:
      Forty patients were treated with surgical resection and postoperative
      radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008.
      Treatment volume was judged by the location of initial tumor and surgical field,
      and 45-50 Gy of radiation was basically delivered and additional dose was
      considered to the high-risk area. RESULTS: The median follow-up period was 41.4
      months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8%
      and disease free survival was 31.5%. The 5-year locoregional recurrence free
      survival was 61.9% and distant metastasis free survival was 50.6%. In univariate
      analysis, histologic type (p = 0.006) was the strongest prognostic factor for the
      OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also
      effect on the OS. Histologic type (p = 0.004) was unique significant prognostic
      factor for the actuarial local control. CONCLUSION: Retroperitoneal sarcoma still
      remains as a poor prognostic disease despite the combined modality treatment
      including surgery and postoperative radiotherapy. Selective dose-escalation of
      radiotherapy or combination of effective chemotherapeutic agent must be
      considered to improve the treatment result especially for the histopathologic
      type showing poor prognosis.

PMID- 22984680
TI  - Pelvic insufficiency fracture after radiotherapy in patients with cervical cancer
      in the era of PET/CT.
AB  - PURPOSE: To determine the incidence, risk factors, and clinical characteristics
      of pelvic insufficiency fracture (PIF) in patients with cervical cancer.
      MATERIALS AND METHODS: Between July 2004 and August 2009, 235 patients with non
      metastatic cervical cancer were treated with definitive chemoradiation or
      postoperative radiotherapy. Among 235 patients, 117 (49.8%) underwent the first
      positron emission tomography/computed tomography (PET/CT) within 1 year after
      radiotherapy. The median radiation dose was 55 Gy (range, 45 to 60 Gy). Medical
      charts and imaging studies, including PET/CT, magnetic resonance imaging (MRI),
      CT, bone scintigraphy were reviewed to evaluate the patients with PIF. RESULTS:
      Among 235 patients, 16 developed PIF. The 5-year detection rate of PIF was 9.5%.
      The 5-year detection rate of PIF in patients who underwent the first PET/CT
      within a year was 15.6%. The median time to development of PIF was 12.5 months
      (range, 5 to 30 months). The sites of fracture included 12 sacroiliac joints, 3
      pubic rami, 3 iliac bones, and 1 femoral neck. Eleven of 16 patients having PIF
      complained of hip pain requiring medications. One patient required
      hospitalization for pain control. The significant risk factors of PIF were old
      age, body mass index less than 23, bone mineral density less than -3.5 SD, and
      the first PET/CT within a year after radiotherapy. Radiation dose and concurrent
      chemotherapy had no impact on PIF rate. CONCLUSION: PIFs were not rare after
      pelvic radiotherapy in cervical cancer patients in the era of PET/CT. Timely
      diagnosis and management of PIF can improve quality of life in patients with
      cervical cancer, in addition to reducing unnecessary medical expenses.

PMID- 22984681
TI  - Volumetric changes in the lumpectomy cavity during whole breast irradiation after
      breast conserving surgery.
AB  - PURPOSE: This study was performed to evaluate the change in the lumpectomy cavity
      volumes before and after whole breast radiation therapy (WBRT) and to identify
      factors associated with the change of volume. MATERIALS AND METHODS: From
      September 2009 to April 2010, the computed tomography (CT) simulation data from
      70 patients obtained before and after WBRT was evaluated. The lumpectomy cavity
      volumes were contoured based on surgical clips, seroma, and postoperative
      changes. Significant differences in the data from pre-WBRT CT and post-WBRT CT
      were assessed. Multiple variables were examined for correlation with volume
      reduction in the lumpectomy cavity. RESULTS: The mean and median volume reduction
      in the lumpectomy cavity after WBRT were 17.6 cm(3) and 16.1 cm(3), respectively
      with the statistical significance (p < 0.001). The volume reduction in the
      lumpectomy cavity was inversely correlated with time from surgery to radiation
      therapy (R = 0.390). The presence of seroma was significantly associated with a
      volumetric change in the lumpectomy cavity after WBRT (p = 0.011). CONCLUSION:
      The volume of lumpectomy cavity reduced significantly after WBRT. As the time
      from surgery to the start of WBRT increased, the volume reduction in the
      lumpectomy cavity during WBRT decreased. A strong correlation was observed
      between the presence of seroma and the reduced volume. To ensure appropriate
      coverage and to limit normal tissue exposure during boost irradiation in patients
      who has seroma at the time of starting WBRT, repeating CT simulation at boost
      planning is suggested.

PMID- 22984682
TI  - Therapeutic results and safety of postoperative radiotherapy for keloid after
      repeated Cesarean section in immediate postpartum period.
AB  - PURPOSE: To evaluate the effectiveness and safety of postoperative radiotherapy
      for the treatment of keloid scars administered immediately after Cesarean
      section. MATERIALS AND METHODS: A total of 26 postpartum patients with confirmed
      keloids resulting from previous Cesarean sections received either 12 or 15 Gy
      radiotherapy. The radiotherapy was divided into three 6 MeV electron beam
      fractions administered during the postpartum period immediately following the
      final Cesarean section. To evaluate ovarian safety, designated doses of radiation
      were estimated at the calculated depth of the ovaries using a solid plate phantom
      and an ionization chamber with the same lead cutout as was used for the treatment
      of Cesarean section operative scars and a tissue equivalent bolus. RESULTS: In
      total, the control rate was 77% (20 patients), while six (23%) developed focally
      elevated keloids (ranging from 0.5 to 2 cm in length) in the middle of the
      primary abdominal scar. Five patients experienced mild hyperpigmentation.
      Nonetheless, most patients (96%) were satisfied with the treatment results. The
      estimated percentage of the applied radiation doses that reached the calculated
      depth of the ovaries ranged from 0.0033% to 0.0062%. CONCLUSION: When
      administered during the immediate postpartum period, postoperative electron beam
      radiotherapy for repeated Cesarean section scars is generally safe and produces
      good cosmetic results with minimal toxicity.

PMID- 22984683
TI  - Clinical application of RapidArc volumetric modulated arc therapy as a component
      in whole brain radiation therapy for poor prognostic, four or more multiple brain
      metastases.
AB  - PURPOSE: To determine feasibility of RapidArc in sequential or simultaneous
      integrated tumor boost in whole brain radiation therapy (WBRT) for poor
      prognostic patients with four or more brain metastases. MATERIALS AND METHODS:
      Nine patients with multiple (>=4) brain metastases were analyzed. Three patients
      were classified as class II in recursive partitioning analysis and 6 were class
      III. The class III patients presented with hemiparesis, cognitive deficit, or
      apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients
      received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by
      sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients
      received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in
      10-20 fractions. RESULTS: The median biologically effective dose to metastatic
      tumors was 68.1 Gy(10) and 67.2 Gy(10) and the median brain volume irradiated
      more than 100 Gy(3) were 1.9% (24 cm(3)) and 0.8% (13 cm(3)) for each group. With
      less than 3 minutes of treatment time, RapidArc was easily applied to the
      patients with poor performance status. The follow-up period was 0.3-16.5 months.
      Tumor responses among the 6 patients who underwent follow-up magnetic resonance
      imaging were partial and stable in 3 and 3, respectively. Overall survival at 6
      and 12 months were 66.7% and 41.7%, respectively. The local progression-free
      survival at 6 and 12 months were 100% and 62.5%, respectively. CONCLUSION:
      RapidArc as a component in whole brain radiation therapy for poor prognostic,
      multiple brain metastases is an effective and safe modality with easy
      application.

PMID- 22984684
TI  - Treatment outcome of conservative surgery plus postoperative radiotherapy for
      extremity soft tissue sarcoma.
AB  - PURPOSE: To evaluate the treatment outcome and prognostic factor of postoperative
      radiotherapy for extremity soft tissue sarcoma (STS). MATERIALS AND METHODS:
      Forty three patients with extremity STS were treated with conservative surgery
      and postoperative radiotherapy from January 1981 to December 2010 at Korea
      University Medical Center. Median total 60 Gy (range, 50 to 74.4 Gy) of radiation
      was delivered and 7 patients were treated with chemotherapy. RESULTS: The median
      follow-up period was 70 months (range, 5 to 302 months). Twelve patients (27.9%)
      sustained relapse of their disease. Local recurrence occurred in 3 patients
      (7.0%) and distant metastases developed in 10 patients (23.3%). The 5-year
      overall survival (OS) was 69.2% and disease free survival was 67.9%. The 5-year
      local relapse-free survival was 90.7% and distant relapse-free survival was
      73.3%. On univariate analysis, no significant prognostic factors were associated
      with development of local recurrence. Histologic grade (p = 0.005) and stage (p =
      0.02) influenced the development of distant metastases. Histologic grade was
      unique significant prognostic factor for the OS on univariate and multivariate
      analysis. Severe acute treatment-related complications, Common Terminology
      Criteria for Adverse Events (CTCAE) grade 3 or 4, developed in 6 patients (14.0%)
      and severe late complications in 2 patients (4.7%). CONCLUSION: Conservative
      surgery with postoperative radiotherapy achieved a satisfactory rate of local
      control with acceptable complication rate in extremity STS. Most failures were
      distant metastases that correlate with tumor grade and stage. The majority of
      local recurrences developed within the field. Selective dose escalation of
      radiotherapy or development of effective systemic treatment might be considered.

PMID- 22984685
TI  - Method of tumor volume evaluation using magnetic resonance imaging for outcome
      prediction in cervical cancer treated with concurrent chemotherapy and
      radiotherapy.
AB  - PURPOSE: To evaluate the patterns of tumor shape and to compare tumor volume
      derived from simple diameter-based ellipsoid measurement with that derived from
      tracing the entire tumor contour using region of interest (ROI)-based 3D
      volumetry with respect to the prediction outcome in cervical cancer patients
      treated with concurrent chemotherapy and radiotherapy. MATERIALS AND METHODS:
      Magnetic resonance imaging was performed in 98 patients with cervical cancer
      (stage IB-IIIB). The tumor shape was classified into two categories: ellipsoid
      and non-ellipsoid shape. ROI-based volumetry was derived from each magnetic
      resonance slice on the work station. For the diameter-based surrogate "ellipsoid
      volume," the three orthogonal diameters were measured to calculate volume as an
      ellipsoid. RESULTS: The more than half of tumor (55.1%) had a non-ellipsoid
      configuration. The predictions for outcome were consistent between two volume
      groups, with overall survival of 93.6% and 87.7% for small tumor (<20 mL), 62.9%
      and 69.1% for intermediate-size tumor (20-39 mL), and 14.5% and 16.7% for large
      tumors (>=40 mL) using ROI and diameter based measurement, respectively. Disease
      free survival was 93.8% and 90.6% for small tumor, 54.3% and 62.7% for
      intermediate-size tumor, and 13.7% and 10.3% for large tumor using ROI and
      diameter based method, respectively. Differences in outcome between size groups
      were statistically significant, and the differences in outcome predicted by the
      tumor volume by two different methods. CONCLUSION: Our data suggested that large
      numbers of cervical cancers are not ellipsoid. However, simple diameter-based
      tumor volume measurement appears to be useful in comparison with ROI-based
      volumetry for predicting outcome in cervical cancer patients.

PMID- 22984688
TI  - Erratum: Acknowledgments correction.

PMID- 22984686
TI  - Effect of troglitazone on radiation sensitivity in cervix cancer cells.
AB  - PURPOSE: Troglitazone (TRO) is a peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist. TRO has antiproliferative activity on many kinds of cancer
      cells via G1 arrest. TRO also increases Cu(2+)/Zn(2+)-superoxide dismutase
      (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation
      sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer
      cells in vitro. MATERIALS AND METHODS: Three human cervix cancer cell lines
      (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase,
      and catalase activities were measured at 2-10 uM of TRO for 24 hours. Cell cycle
      was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured
      using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured
      with clonogenic assay. RESULTS: By 5 uM TRO for 24 hours, the mRNA, protein
      expression and activity of catalase were increased in all three cell lines. G0-G1
      phase cells were increased in HeLa and Me180 by 5 uM TRO for 24 hours, but those
      were not increased in SiHa. By pretreatment with 5 uM TRO radiation sensitivity
      was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2
      uM TRO which increased catalase but not increased G0-G1 cells, radiosensitization
      was not observed. ROS produced by radiation was decreased with TRO. CONCLUSION:
      TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation
      sensitivity through catalase-mediated ROS scavenging according to TRO dose or
      cell types. The change of radiation sensitivity by combined with TRO is not
      dependent on the PPARgamma expression level.

PMID- 22984689
TI  - Erratum: Acknowledgments correction.

PMID- 22984687
TI  - Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated
      receptor alpha-mediated superoxide dismutase induction in HeLa cells.
AB  - PURPOSE: The fibrates are ligands for peroxisome proliferator-activated receptor
      (PPAR) alpha and used clinically as hypolipidemic drugs. The fibrates are known
      to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression
      and catalase activity. The antioxidant actions of the fibrates may modify
      radiation sensitivity. Here, we investigated the change of the radiation
      sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF).
      MATERIALS AND METHODS: Activity and protein expression of SOD were measured
      according to the concentration of FF. The mRNA expressions were measured by using
      real time reverse-transcription polymerase chain reaction. Combined cytotoxic
      effect of FF and radiation was measured by using clonogenic assay. RESULTS: In
      HeLa cells total SOD activity was increased with increasing FF doses up to 30 uM.
      In the other hand, the catalase activity was increased a little. As with activity
      the protein expression of SOD1 and SOD2 was increased with increasing doses of
      FF. The mRNAs of SOD1, SOD2, PPARalpha and PPARgamma were increased with
      increasing doses of FF. The reactive oxygen species (ROS) produced by radiation
      was decreased by preincubation with FF. The surviving fractions (SF) by combining
      FF and radiation was higher than those of radiation alone. In Me180 cells SOD and
      catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and
      PPARalpha were not increased with FF. However, the mRNA of PPARgamma was
      increased with FF. CONCLUSION: FF can reduce radiation sensitivity by ROS
      scavenging via SOD induction in HeLa. SOD induction by FF is related with
      PPARalpha.

PMID- 22984690
TI  - IDENTIFYING AND EVALUATING APRAXIC SPEECH DEFICITS USING MAGNETOMETRY.
AB  - An understanding of the relationship of speech and language symptoms to lesions
      in the frontal region of the dominant hemisphere depends on a fuller description
      of the speech phenomena than can be provided by transcriptional or acoustic
      investigation alone. This paper provides examples of how articulatory movement
      tracking can aid in describing apraxic speech deficits.

PMID- 22984691
TI  - A hybrid computational model for phagocyte transmigration.
AB  - Phagocyte transmigration is the initiation of a series of phagocyte responses
      that are believed important in the formation of fibrotic capsules surrounding
      implanted medical devices. Understanding the molecular mechanisms governing
      phagocyte transmigration is highly desired in order to improve the stability and
      functionality of the implanted devices. A hybrid computational model that
      combines control theory and kinetics Monte Carlo (KMC) algorithm is proposed to
      simulate and predict phagocytes responses at molecular level. In order to mimic
      various biological knockout experiments, a general external control scenario is
      designed. The stochastic nature inherent to phagocyte transmigration is captured
      by KMC. A new formula is derived to calculate the transition rates as inputs to
      KMC. This formulation might quantify biological interactions in a general manner
      which is beyond the scope of the traditional chemical reaction kinetics.

PMID- 22984692
TI  - Facile preparation of allylzinc species from allylboronates and zinc amide via a
      boron-to-zinc exchange process and their reactions with carbonyl compounds,
      imines and hydrazones.
AB  - Facile formation of allylzinc species from allylboronate and zinc amide was
      discovered. The boron-to-zinc exchange process occurred smoothly to afford the
      corresponding allylzinc amides, which were successfully employed in catalytic
      allylation reactions with electrophiles. Asymmetric catalysis using a chiral zinc
      amide is also reported.

PMID- 22984693
TI  - Ion-based materials comprising planar charged species.
AB  - Materials comprising planar units have the propensity to form stacking assemblies
      with nanoscale architectures and intriguing properties. In this feature article,
      some recent examples of ion-based materials comprising positively and negatively
      charged planar species are described. Various ion-based solid and soft materials
      can be formed by planar charged species alone or with the aid of other
      components. It is more challenging to prepare planar anions than planar cations;
      however, the noncovalent association of electronically neutral planar anion
      receptors and anions is an efficient strategy for the preparation of planar
      anions. Suitable candidates include dipyrrolyldiketone boron complexes, which
      exhibit the formation of various receptor-anion complexes and can be used to
      fabricate advanced materials in combination with countercations. Ion-based
      materials consisting of planar charged components have potential as electrically
      conductive materials, resulting from the ordered arrangement of the planar
      charged species.

PMID- 22984694
TI  - Observation of face-to-face host-guest associated states prior to threading of
      dialkylammonium ions into the DB24C8-like openings of a molecular cage.
AB  - The threading of bis(dialkylammonium) ions through the DB24C8-like openings of a
      molecular cage proceeds through a stepwise mechanism: formation of a face-to-face
      complex between the NH2(+) centers and the crown ether, significant dissociation
      of this complex, and passage of the terminus of the cation through the
      macrocycle.

PMID- 22984695
TI  - [I. Current status and problems for clinical path of community network to lung
      cancer].

PMID- 22984696
TI  - [II. Recurrence and second primary lung cancer in patients after resection of
      stage I lung cancer].

PMID- 22984697
TI  - [III. Method and current problem of follow up and future possibility of clinical
      trials for lung cancer-based on practice guideline].

PMID- 22984698
TI  - Findings of research misconduct.

PMID- 22984699
TI  - [The importance of precise impression in implant-supported restoration success].

PMID- 22984700
TI  - [The role of neurogenic factors in the development of chronic recurrent cracks of
      lips].

PMID- 22984701
TI  - [Diagnostic imaging of periodontal bone inflammatory disease].

PMID- 22984702
TI  - Obituary--Janina Dobrzanska (1919-2012).

PMID- 22984703
TI  - Notice of retraction.

PMID- 22984704
TI  - The treatment of recurrent tracheo-oesophageal fistula with biosynthetic mesh.

PMID- 22984705
TI  - Arkansas payment reform... what happens now?

PMID- 22984707
TI  - Health care payment improvement initiative: coming soon to a third party payer
      near you.

PMID- 22984706
TI  - The devil and screening PSA.

PMID- 22984708
TI  - Quality improvement project: hemodialysis vascular access management trends
      report.
AB  - Vascular access for the delivery of hemodialysis is the initial clinical
      procedure for any applicable HD patient. It behooves clinicians to ensure that
      these patients have a vascular access management plan assuring the best permanent
      vascular access possible for optimal patient care outcomes. AVFs are considered
      the preferred access based on their superior patency, minimal complication rates,
      and decreased risk of patient mortality. This project's activities continue to
      address practice barriers and motivate changes where necessary to improve patient
      care.

PMID- 22984709
TI  - Anticoagulants and antiplatelet therapy: 2012 update.

PMID- 22984710
TI  - Pulse oximetry screening for critical congenital heart disease: a review.
AB  - Evidence demonstrates that screening newborns for critical CHD via SpO2 is
      practicable, efficacious, and has excellent sensitivity and specificity. SpO2
      does not detect all forms of CHD, but does detect those presenting with
      hypoxemia. Although SpO2 screening has been recommended at the federal government
      level, states are ultimately responsible for the initiation and management of
      neonatal SpO2 screening programs. Issues of logistics, training and education,
      quality control, and reimbursement remain incompletely addressed but are
      anticipated to be resolved in the near future.

PMID- 22984711
TI  - Intestinal failure improve care project at Arkansas children's hospital.
AB  - Intestinal Failure is a complex and chronic condition that is challenging to
      patients, their families and their physicians. The intestinal rehabilitation team
      at Arkansas Children's Hospital adopts a multidisciplinary approach aimed at
      improving the outcomes of patients with Intestinal failure. The Intestinal
      Failure Improve Care Project will achieve these objectives through care
      coordination and monitoring, education and training of health care providers and
      families, pre-planned visits, and applications of evidence-based guidelines. The
      project will serve as an infrastructure for future clinical and translational
      research in the field.

PMID- 22984712
TI  - Adjusting our moral compass.

PMID- 22984713
TI  - Coding crazies.

PMID- 22984714
TI  - Dentist in a box--states explore the pro and cons of retail dental clinics.

PMID- 22984715
TI  - Dr. Gary A. Uriu. Interview by Bill Scheerer.

PMID- 22984716
TI  - Taking the paperless leap.

PMID- 22984717
TI  - Why your office should be texting.

PMID- 22984718
TI  - Deep and fast: Kerr's SonicFill bulk fill composite.

PMID- 22984719
TI  - 'It may be a hole to you, but it's a socket to me'.

PMID- 22984720
TI  - Are you prepared for retirement?

PMID- 22984721
TI  - MOM brings care, dignity to those most in need.

PMID- 22984722
TI  - Learn to be a good listener and a strong leader.

PMID- 22984723
TI  - What should you do when IDFPR contacts you? Part one of a two-part series.

PMID- 22984724
TI  - Earn a greater return on investing in your community through volunteering.

PMID- 22984725
TI  - Special needs patients.

PMID- 22984726
TI  - Education. Advocacy. Research.

PMID- 22984727
TI  - What patients should know about dental X-rays.

PMID- 22984728
TI  - Ethics and integrity: capstone professional tools.

PMID- 22984729
TI  - An investigation to determine association between foodborne illness and number of
      citations in a food establishment.
AB  - This article analyzes the inspectional data for the food protection program at
      the Cincinnati Health Department prior to the implementation of a standardization
      program for food inspections and food inspection training. The main objectives of
      the authors' study were to assess if current foodborne illness risk factors were
      associated with different risk classes of food establishments and the
      relationships between foodborne illness risk factors using non-Centers for
      Disease Control and Prevention (CDC) foodborne illness risk factors and CDC
      foodborne illness risk factor criteria. Additionally the authors' study provides
      information on whether the standardization of staff reduced the number of risk
      factors at food establishments, reducing the opportunity for a foodborne illness.
      This research compares the mean number of violations cited per inspection at food
      establishments of various risk classes. The authors' findings show that both CDC
      and non-CDC foodborne illness risk factors were positively associated to the risk
      class of the food establishment; however, more non-CDC than CDC foodborne illness
      risk factors were cited by the sanitarians at each level of risk class.

PMID- 22984730
TI  - Are we aware of microbial hotspots in our household?
AB  - Household microorganisms are found in unexpected places. Therefore, the authors
      conducted a study to investigate the microbial hotspots and reveal the
      misconceptions regarding the most contaminated objects in the household. In the
      authors' study, 26 daily use objects in 22 households were sampled to determine
      the levels of heterotrophic plate count (HPC), coliforms, E. coli, yeast and
      mold, and Staphylococcus aureus. High microbial concentration was found in the
      kitchen area and the dish sponge was the most contaminated item in the household,
      followed by the toothbrush holder. Coliforms were most prevalent in the kitchen
      on items such as sponges, sinks, and cutting boards. Yeast and molds were found
      on leather, fabric, porcelain, and laminate, and S. aureus was found on personal
      objects and pet's items. Overall, HPC and the presence of coliforms were
      significantly related to surface type (p < .05). In the kitchen, cleaning
      frequency (p < .03) and type of cleaning (p < .0003) had significant effects on
      HPC. The authors' study provides information that will help the general
      population to make an educated decision in developing a proper and routine
      cleaning regime in their homes. This baseline data might contribute to designing
      appropriate sanitation guidelines or standards that will help to implement proper
      sanitation practices in households and to conducting further research in the area
      of foodborne and household communicable diseases.

PMID- 22984731
TI  - Microbial contamination in 20-peso banknotes in Monterrey, Mexico.
AB  - The authors' aim was to isolate and identify bacteria or yeast that may be
      present on the surface of 20-peso banknotes from the metropolitan area of
      Monterrey, Mexico. They randomly studied a total of 70 20-peso banknotes for the
      presence of bacteria and species of Candida by conventional methods. Out of the
      70 banknotes, 48 (69%) were found to be contaminated. The most prevalent species
      observed was Candida kruseii (19 bills, 27%) followed by Burkholderia cepacia (9
      bills, 13%); 22 (31%) bills showed no growth. Of the 48 contaminated bills, four
      (5.7%) yielded bacteria considered pathogenic and the other 44 bills (63%)
      yielded bacteria considered potentially pathogenic. Eleven bills showed more than
      one microbial species. The results of the authors' study show that contamination
      occurs on paper currency in the metropolitan area of Monterrey. The authors'
      findings provide evidence that currency banknotes may represent a threat to human
      health.

PMID- 22984733
TI  - Plain language summaries: a new EHS-net tool to share our published findings.

PMID- 22984732
TI  - Building capacity for community disaster preparedness: a call for collaboration
      between public environmental health and emergency preparedness and response
      programs.
AB  - Partnerships among local public environmental health (EH), emergency preparedness
      and response (EPR) programs, and the communities they serve have great potential
      to build community environmental health emergency preparedness (EHEP) capacity.
      In the study described in this article, the beliefs and organizational practices
      pertaining to community EHEP outreach and capacity were explored through key
      informant (KI) interviews (N = 14) with a sample of governmental EH and EPR
      administrators and top-level managers from Riverside and San Bernardino counties
      in Southern California. The results indicate that KIs were highly confident in
      their workforces' efficacy, ability, willingness, and motivation to directly
      engage local communities in EHEP. Best practices to combat organizational and
      systematic barriers to community EHEP outreach were identified. Based on the
      authors' results, training in participatory methods is needed to bridge technical
      knowledge in emergency management to daily practice. The lessons learned will
      form the basis of future interventions aimed to prepare EH and EPR professions to
      implement community-focused emergency preparedness strategies.

PMID- 22984734
TI  - Micro jobs and the emerging underground economy.

PMID- 22984735
TI  - The rights of environmental health specialists to conduct on-site inspections.

PMID- 22984736
TI  - From Vilnius, Lithuania, to Las Vegas, Nevada!

PMID- 22984737
TI  - Model approach brings multi-level success.
AB  - n an article that first appeared in US magazine, Medical Construction & Design,
      Mark Howell, senior vice-president of Skanska USA Building, based in Seattle,
      describes the design and construction of a new nine-storey, 350,000 ft2 extension
      to the Good Samaritan Hospital in Puyallup, Washington state. He explains how the
      use of an Integrated Project Delivery (IPD) approach by the key players, and
      extensive use of building information modelling (BIM), combined to deliver a
      healthcare facility that he believes should meet the needs of patients, families,
      and the clinical care team, 'well into the future'.

PMID- 22984738
TI  - Simple maintenance for dramatic effect.
AB  - In an article which first appeared in print in the March 2012 issue of The
      Australian Hospital Engineer, based on a presentation given at the Institute of
      Hospital Engineering Australia's 2009 National Conference, Scott Wells, energy
      manager, Engineering & Building Services, at Royal Brisbane Women's Hospital, and
      Mark Collen, a district account manager, Engineering and Process Development
      Division, at water treatment specialist, Nalco, discuss how sound, regular, and
      thorough, maintenance and cleaning of hospital air-handing units will not only
      enhance their operating efficiency, but will also help reduce airborne infection
      risk in the healthcare facilities they serve. They also detail practical measures
      taken at hospitals in Queensland to reduce the energy consumption of air-handling
      equipment.

PMID- 22984739
TI  - Fuelling innovation in building design.
AB  - Established in 2005 on a 78-acre site near Watford by a research-based
      consultancy, testing, and training organisation with a reputation for
      independence and impartiality, the BRE's Watford Innovation Park is today home to
      a broad range of research, consultancy, and testing activities, for the built
      environment. HEJ editor, Jonathan Baillie, met with BRE director of Strategic
      Research, Peter Ball, to learn about the organisation's history and current-day
      activities, and tour of some of the key facilities where staff undertake cutting
      edge research, consultancy, and testing, to improve the performance, efficiency,
      and sustainability, of a wide range of buildings.

PMID- 22984740
TI  - Putting your trust in sustainable roofing.

PMID- 22984741
TI  - A practical approach to ensuring safe water.
AB  - Susan Pearson BSc reports on a recent specialist waterborne diseases
      'masterclass' held in Nottingham, at which leading experts discussed not only the
      control of Pseudomonas, but also other problematic waterborne pathogens such as
      Legionella, the cause of Legionnaires' disease. The Pall Medical-sponsored event
      provided plenty of 'food for thought' for estates and facilities personnel
      responsible for hospital water systems, and clearly demonstrated how difficult
      and persistent a foe organisms such as Pseudomonas aeruginosa and Legionella
      pneumophila, which, if left unchecked, pose significant patient health risks, can
      be.

PMID- 22984742
TI  - Glan Clwyd operating space is transformed.
AB  - Turnkey construction company, MTX Contracts, has recently completed a suite of
      five 'modern and future-proofed' operating theatres at the Ysbyty Glan Clwyd in
      Bodelwyddan, Denbighshire, in the first phase of a 90-phase, 89.9 million pounds
      sterling redevelopment of facilities at the North Wales hospital being undertaken
      by Laing O'Rourke for the Betsi Cadwaladr University Health Board. According to
      Dr Eileen Williams, a consultant anaesthetist at the hospital, and the clinical
      lead on the hospital redevelopment project, the new theatre facilities will
      enable surgeons to undertake a wide range of surgical procedures, equipped with
      the most modern technology, in an environment that is not only lighter, brighter,
      and better laid out than the six previous theatres, but will also improve patient
      flow, aid infection control, and greatly enhance overall working efficiencies.

PMID- 22984743
TI  - Premier performers for the theatre.
AB  - HEJ editor, Jonathan Baillie, reports on some of the key advances in large
      capital equipment for the operating theatre. Here, he discovered, major drivers
      include continuing growth in the use of laparoscopic and endoscopic surgery,
      increasing demand for the ability to share and stream 'live' audio and video
      footage of innovative surgical techniques to other locations to improve skills
      and boost training, and a general desire to improve efficiency, ergonomics, and
      patient flow.

PMID- 22984744
TI  - Hygienic drainage for healthcare.
AB  - Peter Jennings, technical director for ACO Building Drainage, which specialises
      in the development of corrosion-resistant drainage systems and building products,
      looks at the key issues to consider when specifying and installing pipework and
      drainage for hygiene-critical environments such as hospitals and other healthcare
      facilities.

PMID- 22984745
TI  - Complacency and the cycle of arrogance.

PMID- 22984746
TI  - What does it mean to be a professional nurse?

PMID- 22984747
TI  - A day in the life of advanced practice nurses!

PMID- 22984748
TI  - [Cultural diversity and pluralism in the Universal Declaration on Bioethics and
      Human Rights].
AB  - The Universal Declaration on Bioethics and Human Rights represents a significant
      milestone in the history of Law, particularly in the application of International
      Law to an important area of human activity, namely the medical sciences, the life
      sciences and the technologies which, linked to both, can be applied to human
      relations. In parallel with this, and as will be analysed in this article, the
      Declaration has involved adopting a clear position regarding cultural diversity
      and pluralism in relation to Biomedicine. In this paper the author highlights the
      fact that perspectives have been opened which have hardly been explored
      concerning Biomedicine, such as the recognition of the value and respect which
      cultural diversity (multiculturalism), economic and social diversity deserve in
      relation to the issues covered by the Declaration, and the acceptance that the
      owners of the rights are not only individuals, but can also be groups.

PMID- 22984749
TI  - [Consent in DNA sample harvesting. With special reference to processes with
      minors (Part II)].

PMID- 22984750
TI  - [Contributions for a statute of parts separated from the body].
AB  - In this article the author reflects on the ethical and legal implications arising
      from the treatment that should be conferred on the separate parts of the human
      body. Thus, the status of the body is changing so rapidly, due to the new
      developments in biotechnology, that raises unprecedented dilemmas for the Law.
      Also noteworthy the relevant issues brought by the incessant progress of
      biomedical science, claiming regulations consistent with its implications in
      various fields. The following issues will be highlighted by the author: the
      achievements in the fields of molecular biology and genetics, the proliferation
      and diversification of biobanks, and the commercialization and patenting of
      genes, gene sequences and other biological materials, which generates a series of
      ethical and legal problems.

PMID- 22984751
TI  - The commercialization of human genetic information and related circumstances
      within Turkish law.
AB  - Today, human genetic information is used for commercial purposes as well. This
      means, based on the case, the direct or indirect commercialization of genetic
      information. In this study, this specific issue is analyzed in light of the new
      legal regulations as to the subject in the Turkish Law. Specifically, this study
      focuses on the issue of whether the commercialization of genetic information is
      allowed under the Turkish Law. This study also attempts to clarify the issue of
      whether there is any limitations for the commercialization of genetic information
      in the Turkish Law provided that the commercialization of genetic information is
      permitted. Prior to this legal analysis, the problems of the legal ownership for
      genetic information and of whether genetic information should be considered as an
      organ of human body is discussed. Accordingly, relevant Turkish laws and
      regulations are individually analyzed within this context. In the mean time legal
      regulations of some countries in this respect are taken into account with a
      comparative approach. In the end a general evaluation and suggestions are
      provided to the reader.

PMID- 22984752
TI  - [Rare diseases: specific ethical and legal aspects of genetic counseling and
      screening].
AB  - This article analyses the specific rights of patients with rare diseases from a
      dual perspective. On the one hand, they concern a new generation of patients'
      rights that arise once the consolidation of basic rights has occurred,
      fundamentally after the application of Law 41/2002 (on Regulating Patient
      Autonomy and Rights and Obligations in the Field of Health Documentation and
      Information) and its development by the autonomous communities. On the other
      hand, the fundamental question raises a serious issue related to these patients,
      which involves the principles of equality, equity, non-discrimination and
      solidarity. This is aimed at promoting legislative measures to protect patients'
      equality of access to health and social services, with the ultimate aim of
      improving their quality of life. The author has given special relevance in his
      study to the treatment of rare diseases that are genetic in origin, and to the
      importance of adequate genetic counseling.

PMID- 22984753
TI  - [Decision of the Court of Justice of the European Union on embryonic stem cell
      patents. On a legal report on patents: the concept and dignity of the human
      embryo].
AB  - The Advocate General of the European Court of Justice's opinion on the
      patentability of embryo pluripotent stem cells according to the 98/44/CE
      Directive (Art. 6.2.c) is analyzed. Scientific, ethical and legal considerations
      on human embryos and stem cells are included.

PMID- 22984754
TI  - [Informed consent for genetic information management in Colombian law].
AB  - Deciphering the human genome has allowed the development of new health care ways
      which have been generically referred to as genomic medicine. However, this new
      knowledge is not devoid of risks related to the access and use of genetic
      information, involving not only the individual, but also the biological family,
      ethnic group and community to which he/she belong to. This affects both
      individual and collective rights, which must be protected by law. This manuscript
      reviews the Colombian law, specifically in terms of the access and use of genetic
      information for diagnostic and treatment purposes, focusing on the informed
      consent process. The concept of genetic information, the risks and benefits
      associated with genetic data management and the description and critical analysis
      of the present Colombian regulations were thus reviewed. As a conclusion, the
      juridical framework of Colombia shows deficiencies regarding the protection of
      both individual and collective rights linked to the access and use of genetic
      information.

PMID- 22984755
TI  - Human genome and open source: balancing ethics and business.
AB  - The Human Genome Project has been completed thanks to a massive use of computer
      techniques, as well as the adoption of the open-source business and research
      model by the scientists involved. This model won over the proprietary model and
      allowed a quick propagation and feedback of research results among peers. In this
      paper, the author will analyse some ethical and legal issues emerging by the use
      of such computer model in the Human Genome property rights. The author will argue
      that the Open Source is the best business model, as it is able to balance
      business and human rights perspectives.

PMID- 22984756
TI  - [Decision of the Justice Court (Great Chamber) of October 18, 2012 - Oliver
      Brustle vs Greenpeace eV].

PMID- 22984757
TI  - [How to explore a fever of unknown origin in adult patients?].
AB  - Fever of unknown origin (FUO), with more than 200 potential causes, can represent
      a real diagnostic challenge. For the work-up of FUO, the first step is to pay
      attention to each element revealed by a detailed history, a complete physical
      examination and by some basic diagnostic tests. These elements may constitute
      some clues that can guide the physician for the prescription of further
      appropriate diagnostic examinations and procedures. If there is no real specific
      clues,a pet-scan seems to be useful for the work-up of FUO.

PMID- 22984758
TI  - [Clinical case of the month. A complicated infective endocarditis, diagnosis,
      treatment and prophylaxis].
AB  - The case of a 60-year-old male presenting fever of recent onset is reported. He
      had undergone a Bentall operation seven yeasr previously. An infective
      endocarditis caused by Entercoccus Faecalis was detected on his prosthetic valve.
      After a favorable evolution under antibiotic treatment, the patient developed a
      perivalvular abscess requiring surgical treatment. The patient's evolution was
      satisfactory. Diagnosis, with the specific role of echocardiography; treatment,
      with a recall of surgical indications; particularities of the specific
      complication and prevention of this pathology are discussed.

PMID- 22984760
TI  - [Follow up of adults with congenital heart disease].
AB  - During the last decades, the care of children with congenital heart disease has
      markedly improved. In consequence, the number of those who reach adulthood is
      continuously growing. In 2010, the European Society of Cardiology published
      guidelines for the management of grown-up congenital heart disease (GUCH) and
      recommended that each GUCH patient should be examined at least once in a
      specialized center. Due to their specific needs, this population requires
      specific and organized care. Indeed, GUCH patients do not only have significant
      extra-cardiac problems, but also present specific cardiac complications such as
      right ventricular failure, incisionnal arrhythmias. They may require repeated
      surgical and/ or percutaneous interventions. Since this emerging population is
      ageing, they also may suffer from arterial hypertension, diabetes and coronary
      artery disease. Last but not least, young women with congenital heart disease
      need specialized advice and care for contraception, follow-up during pregnancy
      and peripartal management. In order to optimize the follow-up of this growing
      population, a shared care model where cardiologists, specialized GUCH centers and
      other specialized centers for the treatment of extra-cardiac problems work in
      tight collaboration is recommended.

PMID- 22984759
TI  - [Clinical case of the month. Mild hemolytic disease of the newborn due to an anti
      Wr(a) antibody].
AB  - A Caucasian woman, with a A+ CCD.ee K neg erythrocyte phenotype and no history of
      blood transfusion, delivered a first child who developed mild anemia. The direct
      antiglobulin test performed on the newborn red blood cells belonging to the A+
      CCD.ee K neg group, was strongly positive for IgG. During the pregnancy and after
      the delivery, the woman had a negative irregular antibody screening test, using
      standard red blood cells. However, at birth, using a collection of thawed red
      blood cells with rare phenotypes (private antigens), the lab showed an antibody
      anti-Wr(a) in the maternal serum. The activity of the maternal antibody, with a
      titer of 16, was completely inhibited by dithiothreitol, indicating the nature
      IgM of the circulating antibody. The presence of the antigen Wr(a) on the surface
      of the newborn and its biological father red blood cells was confirmed. The
      concentration of IgG anti-Wr(a) on baby erythrocytes was demonstrated by the
      presence of the antibody anti-Wr(a) in the eluate. This case illustrates the
      difficulties to detect antibodies against private antigens on baby erythrocytes,
      responsible of hemolytic diseases of newborn. Indeed, standard red blood cell
      panels used for irregular antibodies screening test do not express generally
      those private antigens.

PMID- 22984761
TI  - [Premature ovarian failure, from genetics to clinical].
AB  - Premature Ovarian Failure (POF) is a condition with complicated clinical
      presentation. An estimated 1% of the population is affected before the age of 40,
      with 0.1% affected prior to the age of 30. There are many causes of POI: genetic
      aberrations, auto-immune ovarian damage, iatrogenic factors following surgery,
      radiotherapy or chemotherapy, environmental factors (viruses, toxins, smoking)
      and metabolic. The majority of POF cases have idiopathic etiologies.

PMID- 22984762
TI  - [Temporomandibular joint diseases].
AB  - Why are patients liable to suffer from craniomandibular disorders? What are the
      various local and global consequences? What is the part played by bruxism and
      craniofacial traumas in the aetiology of cranio-mandibular disorders? What is the
      contribution that can be expected from MI in this diagnosis? What are the various
      treatments that can be taken into consideration? These are all questions that the
      GPs could ask themselves concerning TMJ and related disorders.

PMID- 22984763
TI  - [Primary retroperitoneal fibrosis: a report of 7 cases].
AB  - Retroperitoneal fibrosis is a rare fibrosing disease of the retroperitoneal
      tissue characterized by a significant clinico-biological polymorphism. No
      codified treatment exists, particularly for the primary type which is the most
      frequent. We retrospectively report on 7 cases of primary retroperitoneal
      fibrosis seen over a period of 10 years. There were 4 men and 3 women (mean age:
      58 years).The most common presenting symptom was lumbar pain. A biological
      inflammatory syndrome and a renal insufficiency were found in 4 cases. The
      diagnosis was confirmed by abdominal CT scan and/or histology. Etiological
      investigations remained negative. The evolution was generally favourable under
      corticosteroids. Retroperitoneal fibrosis requires a careful etiological
      investigation before it is considered primary. Prognosis is good in spite of the
      absence of a well codified treatment.

PMID- 22984764
TI  - [Clinical, radiographic and biologic particularities of ankylosing spondylitis in
      Tunisian patients according to the presence or the absence of the HLA B27 and its
      sub-types].
AB  - To assess the clinical, radiographic and biologic particularities of ankylosing
      spondylitis (AS) in Tunisian patients according to HLA B27 and its sub-types
      statute. This was a case-control study that included 100 patients (85 males/15
      females) with AS according to the modified New York criteria. Demographic,
      clinical, AS specific indexes, radiographic and biologic parameters were
      determined. HLA-B and B27 subtypes typing of all subjects were performed by PCR
      SSP. Patients mean age was 38.4 years +/- 12.6 HLA-B27 was found in 62% of
      patients. The comparison of B27 positive and B27 negative patients revealed a
      correlation of B27 with age, male gender, family history of spondylarthropathies,
      age at disease onset, acute onset of the disease, inaugural spinal involvement,
      uveitis, bilateral and destructive hip arthritis as well as a high score of
      mSASSS. The most frequent sub-types of HLA B27 were B*2702 (49.2%) and B*2705
      (36.3%). No significant difference of the clinical presentation of the disease or
      severity factors was found among these patients. This study confirmed the
      contribution of the HLA B27 to the determination of the clinical presentation of
      AS. The variability of factors linked to B27 may be explained by the polygenic
      model of the disease.

PMID- 22984765
TI  - [Pazopanib (Votrient) in the management of renal cell cancer and soft tissue
      sarcomas].
AB  - Renal cell carcinoma accounts for 3% of all malignant tumors. Until a few years
      ago, immunotherapy (Interferon and/or Interleukin-2) was the only approved
      systemic treatment in the metastatic setting. Better knowledge of renal cell
      cancer biology drew attention on the fundamental role of angiogenesis. Several
      strategies targeting angiogenesis have been developed including VEGF and VEGFR
      inhibitors. They are now the standard treatment in first and second line.
      Pazopanib, a VEGFR tyrosine kinase inhibitor, is one of the treatment options
      recommended for patients with metastatic renal cell carcinoma, in first line and
      after cytokines failure. Since more recently, pazopanib is also approved in the
      treatment of metastatic soft tissue sarcoma, after failure of at least one line
      of chemoterapy. In this paper, we will review the mechanism of action and the
      clinical results of pazopanib in renal cell carcinoma and sarcoma.

PMID- 22984766
TI  - [The role of the type-three secretion system of the gram-negative bacteria in
      regulation of chronic infections].
AB  - The role of the type-three secretion system of the gram-negative bacteria in
      regulation of chronic infections is discussed. Recent research showed that most
      of severe chronic somatic diseases are derived from chronic infection induced in
      the first place by infectious agents. The role of the T3SS of different species
      in transition from an acute infection to persistence is reviewed. Clinical and
      bacteriological research showed that microorganisms are persistent in the form
      resistant to antibiotics. That is why one of the promising targets for the
      development of antibacterial new-generation treatment is T3SS that conducts
      transport of bacteria pathogenicity factors into eukaryotic cell. The presence of
      this structure is necessary for the development of an acute infectious process
      and chronization of an infection is essential for its functioning.

PMID- 22984767
TI  - Popular molecular markers in bacteria.
AB  - Molecular markers are defined as the fragments of DNA sequence associated with a
      genome, which areused to identify a particular DNA sequence. Nowadays, with the
      explosive growth of genetic research and bacterial classification, molecular
      marker is an important tool to identify bacterial species. Taking account to its
      significant roles in clinic, medicine and food industry, in this review article,
      we summa rize the traditional research and new development about molecular
      markers (also called genetic markers) in bacteria, including genes of 16S rRNA,
      23S rRNA, rpoB, gyrB, dnaK, dsrAB, amoA, amoB, mip, horA, hitAM, recA, ica, frc.
      oxc, 16S-23S rDNA ISR and IS256.

PMID- 22984768
TI  - [The phylogeography of the Yersinia pestis vole strains isolated from the natural
      foci of caucasian region].
AB  - 57 Y pestis bv. caucasica strains were assayed using molecular typing. The
      results of these assays indicated the presence within this biovar of the three
      separate clonal clusters and necessity of detachment of the Leninakan mountain
      mesofocus (subfocus) from the structure of Transcaucasian-highland focus into
      self-supporting one, as well as inclusion of a part of the Pre-Araks low-mountain
      natural plague focus in the capacity of the subfocus along with Pre-Sevan
      mountain and Zanzegur-Karabakh mountain subfoci into the structure of
      Transcaucasian-highland focus. It was shown that the strains circulating in the
      East-Caucasian highland plague focus were the most ancient branch of bv.
      caucasica or even of the entire Y pestis phylogenetic tree.

PMID- 22984769
TI  - [The components of Francisella tularensis protective antigene complex].
AB  - The structural characteristics of Francisella tularensis protective antigene
      complex (PAC) were discussed. PAC is the water-soluble antigene of outer
      membranes F. Tularensis with sophisticated chemical nature. The molecular weight
      of PAC is 280 kD. It was found that PAC is composed of some immunoreactivity
      protein subunits with molecular weight from 81 to 19 kD, and 14-17 kD lipoprotein
      subunit. The stress proteins-chaperones (GroES, GroEL), outer membrane proteins
      (FTL_0617, OmpH), receptor proteins (EF Tu, Rp1L), bacterial enzymes (KatG,
      GAPDH), and lipopolysaccharide were identified in the PAC structure. Their
      presence determines the PAC high immunobiological activity.

PMID- 22984770
TI  - [Specific motifs in the genomes of the family Chlamydiaceae].
AB  - Specific motifs in the genomes of the family Chlamydiaceae were discussed. The
      search for genetic markers ofbacteria identification and typing is an urgent
      problem. The progress in sequencing technology resulted in compilation of the
      database of genomic nucleotide sequences of bacteria. This raised the problem of
      the search and selection of genetic targets for identification and typing in
      bacterial genes based on comparative analysis of complete genomic sequences. The
      goal of this work was to implement comparative genetic analysis of different
      species of the family Chlamydiaceae. This analysis was focused to detection of
      specific motifs capable of serving as genetic marker of this family. The
      consensus domains were detected using the Visual Basic for Application software
      for MS Excel. Complete coincidence of segments 25 nucleotide long was used as the
      test for consensus domain selection. One complete genomic sequence for each of 8
      bacterial species was taken for the experiment. The experimental sample did not
      contain complete sequence of C. suis, because at the moment of this research this
      species was absence in the database GenBank. Comparative assay of the sequences
      of the C. trachomatis and other representatives of the family Chlamydiaceae
      revealed 41 common motifs for 8 Chlamydiaceae species tested in this work. The
      maximal number of consensus motifs was observed in genes of ribosomal RNA and t
      RNA. In addition to genes of r-RNA and t-RNA consensus motifs were observed in 5
      genes and 6 intergene segments. The gene CTL0299, CTLO800, dagA, and hctA
      consensus motifs detected in this work can be regarded as identification domains
      of the family Chlamydiaceae.

PMID- 22984771
TI  - [Studying of molecular mechanisms of rubella virus attenuation evidence from
      Russian strain C-77].
AB  - Live attenuated rubella vaccine is used for vaccination. Temperature-sensitive
      (ts) phenotype was proved for almost all rubella vaccine strains, and the
      acquisition of the ts phenotype during cold adaptation was strongly correlated
      with the attenuation of the wild-type viruses. Nevertheless, the molecular
      mechanisms of the attenuation have been insufficiently understood for rubella
      virus. Study ofthese mechanisms, identifying genotypic markers of attenuation,
      which together with the sequence analyses could be used for genetic stability
      control of vaccine strains, is still of current interest. In this work, we
      determined nearly complete genome sequences of attenuated (ca) and the wildtype
      progenitor (wt) of the rubella virus strain C-77 isolated in Russia. Possible
      genetic determinants of attenuation were detected. Thus, 13 nucleotide
      differences leading to 6 amino acid substitutions were found. Four amino acid
      substitutions were found to be almost unique. Special consideration should be
      given to Tyr1042Cys substitution in the protease domain of C-77 strain, because
      it most probably plays the crucial role in acquisition of ts-phenotype.

PMID- 22984772
TI  - [New genotype of the sacbrood virus of the honeybee Apis mellifera].
AB  - The sacbrood virus (SBV) leads to death of honeybee larvae. Until now, there were
      known three SBV genotypes: European, Asian, and South African (E. Grabensteiner
      et al., 2001; S. E. Choe et al., 2012). Serologic assay, sequencing and
      phylogenetic analysis of the SBV RNA-polymerase gene fragments resulted in
      discovery of two genotypes of SBV circulating among the honeybee Apis mellifera
      in the European region of Russian Federation (RF). One of them forms a new
      distinct genetic lineage of SBV (genotype 4), which has not been described before
      and has an intermediate position between the Asian and the South African
      genotypes on a phylogenetic tree. The viruses belonging to this group were
      isolated from honeybee in Kaluga region in 1986, and in 2006 from honeybee
      introduced earlier to Moscow from Uzbekistan. The sequence homology inside this
      group is 94.2%, whereas this one between different groups is not higher then 80.6
      83.5%. Another group represents the European genotype of SBV circulating in
      Krasnodar Territory, Adyghe Republic, and Moscow region. Two SBV genotypes from
      Russian Federation can be differentiated using PCR and radial immunodiffusion
      test (RID). As for RID, both genotypes react with antiserum #6(1), but only the
      fourth genotype reacts with antiserum #58.

PMID- 22984773
TI  - A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome.
AB  - We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and
      evaluate the genotype-phenotype correlation. BS is caused by mutations in up to
      10 different genes, SCN5A being the most frequently involved. Large genomic
      rearrangements in SCN5A have been associated with conduction disease, but its
      prevalence in BS is unknown. Seventy-six non-related patients with BS were
      studied. Clinical characteristics and family risk profile were recorded. Direct
      sequencing and multiplex ligation-dependent probe amplification (MLPA) of the
      SCN5A gene for identification of mutations and larger rearrangements were
      performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K,
      G1743R (detected in three families), V728I, N1443S and E1152X). Patients with
      mutations had a trend toward a higher proportion of spontaneous type I Brugada
      electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial
      disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the
      carriers were not different from wild-type probands. There were non-significant
      differences in the prevalence of type I ECG, syncope and history of arrhythmia in
      carriers of selected polymorphisms. None of the patients had any
      deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had
      mutations in the SCN5A gene. Patients with mutations seemed to have more
      spontaneous type I ECG, but no differences in syncope or arrhythmic events
      compared with patients without mutations. Larger studies are needed to evaluate
      the role of polymorphisms in the SCN5A in the expression of the phenotype and
      prognosis. Large rearrangements were not identified in the SCN5A gene using the
      MLPA technique.

PMID- 22984774
TI  - On the interaction of acetone with electrophilic metallocavitands having extended
      cavities.
AB  - We report the synthesis and characterization of tantalum-boronate trimetallic
      clusters of  general formula {[Cp*Ta](3)(MU(2)-RB(O)(2))(3)(MU(2)-OH)(MU(2)
      O)(2)(MU(3)-OH)} (R= 4-(C(6)H(5))(C(6)H(4)) (Ta(3)-4Ph), 4-(C(6)H(5)O)(C(6)H(4))
      (Ta(3)-4OPh), 4-(C(7)H(7)O)(C(6)H(4)) (Ta(3)-4OBn), 4-(C(8)H(5))(C(6)H(4)) (Ta(3)
      4PhEt), and 4-(C(12)H(7))(C(6)H(4)) (Ta(3)-4Napht)). All complexes have been
      characterized by NMR spectroscopy and X-ray diffraction. The trimetallic species
      feature a large Lewis acid type cavity allowing for substrate binding in both the
      solid and the liquid state using a unique electrostatic interaction and a
      hydrogen bond.  DeltaH degrees  and DeltaS degrees  values for  association of
      acetone with the complexes vary between -2.0 and -4.1 kcal.mol(-1) and -3 and 2
      cal.mol(-1).K(-1), respectively, showing weaker binding than smaller cavitands of
      the same type. The barrier for  acetone exchange at equilibrium is similar for
      all complexes, and  DeltaH(?) values vary between 8.2 and 11.4 kcal.mol(-1).

PMID- 22984775
TI  - Promoting women's health in a complex world.

PMID- 22984776
TI  - Twin-twin transfusion syndrome: the good news is; there is still room for
      improvement ....

PMID- 22984777
TI  - Structure and biosynthesis of the antibiotic bottromycin D.
AB  - Drug resistant infectious diseases are quickly becoming a global health crisis.
      While Streptomyces spp. have been a major source of antibiotics over the past 50
      years, efficient methods are needed to identify new antibiotics and greatly
      improve the rate of discovery. LCMS-based metabolomics were applied to analyze
      extracts of 50 Streptomyes spp. Using this methodology, we discovered bottromycin
      D and used whole genome sequencing to determine its biosynthesis by a ribosomal
      pathway.

PMID- 22984778
TI  - Effects of natural mating and CO2 narcosis on biogenic amine receptor gene
      expression in the ovaries and brain of queen honey bees, Apis mellifera.
AB  - A queen honey bee mates at ~6 days of age, storing the sperm in her spermatheca
      for life. Mating is associated with profound changes in the behaviour and
      physiology of the queen but the mechanisms underlying these changes are poorly
      understood. What is known is that the presence of semen in the oviducts and
      spermatheca is insufficient to initiate laying, and that copulation or CO(2)
      narcosis is necessary for ovary activation. In this study we use real-time
      quantitative PCR to investigate the expression of biogenic amine receptor genes
      in the brain and ovarian tissue of queens in relation to their reproductive
      status. We show that dopamine, octopamine and serotonin receptor genes are
      expressed in the ovaries of queens, and that natural mating, CO(2) narcosis, and
      the presence of semen in the spermatheca differentially affect their expression.
      We suggest that these changes may be central to the hormonal cascades that are
      necessary to initiate oogenesis.

PMID- 22984779
TI  - Emerging HIV epidemic among older adults in Nanning, China.
AB  - The HIV/AIDS surveillance data indicates that the proportion of people living
      with HIV/AIDS (PLWHAs) who were 50 years old or older increased to 42.7% in 2011
      from 16.5% in 2007 in Nanning, the capital city of Guangxi Province. A greater
      number of newly diagnosed HIV cases compared to clinical AIDS cases were
      identified from older adults. The dominant HIV transmission mode among older
      PLWHAs was heterosexual although approximately 30% of all PLWHAs acquired HIV
      through heterosexual contacts.

PMID- 22984780
TI  - Feasibility, acceptability, and preliminary efficacy of the unity workshop: an
      internalized stigma reduction intervention for African American women living with
      HIV.
AB  - Observational studies have examined the prevalence and impact of internalized
      stigma among African American women living with HIV, but there are no
      intervention studies investigating stigma reduction strategies in this
      population. Based on qualitative data previously collected, we adapted the
      International Center for Research on Women's HIV Stigma Toolkit for a domestic
      population of African American women to be consistent with Corrigan's principles
      of strategic stigma change. We implemented the intervention, led by an African
      American woman living with HIV, as a workshop across two afternoons. The
      participants discussed issues "triggered" by videos produced specifically for
      this purpose, learned coping mechanisms from each other, and practiced them in
      role plays with each other. We pilot tested the intervention with two groups of
      women (total N=24), measuring change in internalized stigma with the Stigma Scale
      for Chronic Illness before and after workshop participation. Sixty-two percent of
      the participants self-reported acquiring HIV through heterosexual sexual contact,
      17% through intravenous drug use, 4% in utero, and 13% did not know the route of
      transmission. The intervention was feasible, enthusiastically accepted by the
      women, and led to decreased stigma from the start of the workshop to the end
      (p=0.05) and 1 week after (p=0.07) the last session of workshop. Findings suggest
      the intervention warrants further investigation.

PMID- 22984781
TI  - Psychological response to multifetal reduction and pregnancy termination due to
      fetal abnormality.
AB  - OBJECTIVE: To investigate the emotional response in cases of multifetal reduction
      and pregnancy termination and to compare the psychological response between these
      two groups. METHODS: A prospective study in a tertiary-care, university
      affiliated medical center. The study group included 65 women who had been advised
      to terminate pregnancy because of a finding of a severe fetal abnormality on
      ultrasound screening (pregnancy termination group) and 41 women advised to
      undergo reduction because of the presence of multiple fetuses (multifetal
      reduction group). All women underwent psychological testing using validated
      questionnaires addressing perinatal grief and anxiety levels. RESULTS: Women in
      both the multifetal reduction and the pregnancy termination groups reported
      significant degree of grief and anxiety before and after the procedure, although
      the levels of anxiety on the day of procedure and anxiety and grief at follow up
      were higher in the pregnancy termination group (t = 2.438, p = 0.016; t = 2.441,
      p = 0.017; and t = 3.111, p = 0.03, respectively). In both groups there was a
      gradual decrease in the state anxiety with time (48.01 +/- 8.26 to 37.59 +/-
      9.23; t = -9.931; p < 0.001). Several factors affected the emotional response in
      the cases, including marital status, level of education, employment status, and
      gestational age. There was no association between a history of prior perinatal
      loss and emotional response. CONCLUSION: There is need for a continuing
      psychosocial support of women undergoing multifetal reduction and pregnancy
      termination for fetal abnormalities.

PMID- 22984783
TI  - Effect of mica reinforcement on the flexural strength and microhardness of
      polymethyl methacrylate denture resin.
AB  - PURPOSE: Conventional denture base polymethyl methacrylate (PMMA) is low in
      strength, soft, and brittle on impact. Improvements in the mechanical properties
      of denture base materials have been sought by adding different reinforcing phases
      to the PMMA matrix. The purpose of this work was to study the effects of mica
      reinforcement on the mechanical properties, flexural strength, and microhardness
      of PMMA denture base resin. MATERIALS AND METHODS: Wet ground muscovite mica and
      Lucitone 199 original shade denture base resin were used. Two micas were tested:
      W200 and P66 with average particle sizes (d50) of 131 MUm and 30 MUm,
      respectively. The mica was silane treated in a solution of 3-methacryloxypropyl
      trimethoxysilane, ethanol, and water, and then dried. The specimens were
      fabricated using the denture base resin manufacturer's instructions with a powder
      : liquid ratio of 21 g/10 ml and a mixing time of 30 seconds. Five treatment
      groups were produced with differing amounts of mica added to the PMMA denture
      base resin: (A) control group with 0 vol% mica, (B) 10 vol% W200 mica, (C) 20
      vol% W200 mica, (D) 10 vol% P66 mica, (E) 20 vol% P66 mica. The mica replaced
      equal volumes of the PMMA powder component to minimize changes in viscosity. The
      three-point bending flexural strength specimens were 70 * 11 * 3 mm(3) . Seven
      specimens were prepared for each treatment group. The hardness specimens were
      prepared from the ends of the three-point bend specimens after they were broken
      (N = 7). After deflasking, the specimens were polished with 600 grit silicon
      carbide paper to achieve smooth surfaces. A standard three-point bending jig with
      a span length of 50 mm was attached to an Instron universal testing machine. The
      specimens were placed on the jig, and loading was carried out using a 1 mm/min
      crosshead speed until failure. Microhardness was measured using a Clark
      microhardness tester with a Knoop indenter. The load was set to 200 g and the
      dwell time to 15 seconds. ANOVA and Tukey tests were used for statistical
      analyses (Alpha = 0.05). RESULTS: The flexural strength of the control group was
      between 77% and 94% higher than all the mica-containing groups (p<= 0.05). No
      significant differences were found within the four mica groups. Microhardnesses
      of the 20% mica groups (both fine and coarse) were 33% and 26% higher than the
      control (p<= 0.05). The 10% mica groups had higher hardness than the control
      group, but the increase was not statistically significant (p > 0.05). CONCLUSION:
      Mica additions to denture PMMA reduced flexural strength; however, with the
      specimens containing highest mica concentrations (20%), microhardness
      significantly increased.

PMID- 22984782
TI  - High-throughput sequencing of black pepper root transcriptome.
AB  - BACKGROUND: Black pepper (Piper nigrum L.) is one of the most popular spices in
      the world. It is used in cooking and the preservation of food and even has
      medicinal properties. Losses in production from disease are a major limitation in
      the culture of this crop. The major diseases are root rot and foot rot, which are
      results of root infection by Fusarium solani and Phytophtora capsici,
      respectively. Understanding the molecular interaction between the pathogens and
      the host's root region is important for obtaining resistant cultivars by
      biotechnological breeding. Genetic and molecular data for this species, though,
      are limited. In this paper, RNA-Seq technology has been employed, for the first
      time, to describe the root transcriptome of black pepper. RESULTS: The root
      transcriptome of black pepper was sequenced by the NGS SOLiD platform and
      assembled using the multiple-k method. Blast2Go and orthoMCL methods were used to
      annotate 10338 unigenes. The 4472 predicted proteins showed about 52% homology
      with the Arabidopsis proteome. Two root proteomes identified 615 proteins, which
      seem to define the plant's root pattern. Simple-sequence repeats were identified
      that may be useful in studies of genetic diversity and may have applications in
      biotechnology and ecology. CONCLUSIONS: This dataset of 10338 unigenes is
      crucially important for the biotechnological breeding of black pepper and the
      ecogenomics of the Magnoliids, a major group of basal angiosperms.

PMID- 22984784
TI  - Stereochemical study of a transannular Michael reaction cascade.
AB  - We systematically explored a transannular Michael reaction cascade for
      stereoselective synthesis of polycyclic systems. Both E,Z- and E,E-1,7-bis-enones
      in the form of 14-membered macrocyclic lactones underwent transannular
      cyclization to give polycyclic products with high efficiency and excellent
      diastereoselectivity. In contrast, Z,E- and Z,Z-macrocyclic lactones did not
      cyclize under similar reaction conditions. Our study revealed similarities and
      subtle stereochemical differences between this transannular cyclization process
      and transannular Diels-Alder reactions. An acyl ketene approach was developed for
      efficient synthesis of macrocyclic lactones. This investigation also illuminated
      the scope and limitation of macrocyclization by intramolecular Reformatsky
      reaction to prepare macrocyclic lactones.

PMID- 22984785
TI  - Critical role of prostate biopsy mortality in the number of years of life gained
      and lost within a prostate cancer screening programme.
AB  - Study Type--Therapy (data synthesis) Level of Evidence 2b. What's known on the
      subject? and What does the study add? The efficacy of prostate cancer screening
      using PSA testing is still being debated, with conflicting results in randomized
      trials. The study shows that, even using the hypothesis most favourable to
      prostate cancer screening with PSA, the net number of years of life does not
      favour screening. OBJECTIVE: * To evaluate the impact of the implementation a
      prostate-specific antigen (PSA) screening programme using the European Randomized
      Study of Screening for Prostate Cancer (ERSPC) results and taking into account
      the impact of prostate biopsy and over-treatment on mortality. MATERIALS AND
      METHODS: * We used a model based on the number of years of life gained and lost
      owing to screening, using data reported in the ERSPC. * We conducted a critical
      evaluation of the ERSPC results and of the Swedish arm of the study. RESULTS: * 
      Accounting for biopsy-specific mortality and for over-treatment, the balance of
      number of years of life was negative in the ERSPC study, with an estimated loss
      of 3.6 years of life per avoided death. * The number of years of life becomes
      positive (real gain) only when fewer than 666 screened individuals are required
      to avoid one death. * We found that in the Swedish arm of the ERSPC there was a
      biopsy rate of 40% compared with 27% in the ERSPC overall. The over-treatment
      rate was also greater with 4.1% compared with 3.4% overall. * For the last 20
      years, there has been a marked difference in prostate cancer-specific mortality
      between Sweden and the rest of Europe: in 2005, for the age group 65-74 the rate
      was 140 per 100,000 person years in Sweden and ~80 per 100,000 for the rest of
      Europe. CONCLUSION: * Overall, PSA testing in Europe is associated with a loss in
      years of life and should thus not be recommended.

PMID- 22984786
TI  - Introduction of William F. Font, recipient of the 2012 Clark P. Read Mentor
      Award.

PMID- 22984787
TI  - Specific immunotherapy can greatly reduce the need for systemic steroids in
      allergic rhinitis.
AB  - BACKGROUND: Worldwide, more than 400 million individuals have allergic rhinitis,
      which has a significant impact on the individual's general health. Most patients
      self-medicate with over-the-counter drugs, but severe cases need treatment with
      topical corticosteroids and/or immunotherapy (SCIT). Although the ARIA guidelines
      discourage the use of systemic corticosteroids, this treatment is often used by
      general practitioners. AIMS: To investigate the use of systemic steroids to treat
      allergic rhinitis in Denmark and the role of SCIT as an alternative. METHODS: A
      retrospective study based on Danish National Registry databases 1995-2009.
      Steroid use was defined as a minimum of one steroid injection during April-July
      for at least three consecutive years. SCIT treatment against grass (Phleum
      pratense), birch (Betula verrucosa) or both was included. RESULTS: Overall, 39
      173 individuals were treated with either SCIT or steroids; 93.1% received only
      steroids, and 6.9% received SCIT and/or steroids. The steroid-to-SCIT ratio was
      14 : 1 (P < 0.0001). The mean annual steroid injections were 1.6 in the steroid
      only group and 1.0 in the SCIT group (P < 0.0001). Of the SCIT-treated
      individuals, 84% did not need steroids after SCIT treatment (P < 0.0001). The
      hazard ratios of receiving steroids after SCIT against grass, birch or both were
      0.65, 0.83 and 0.72, respectively (P < 0.0001), when compared with the steroids
      only group. The maximum hazard reduction was obtained if patients responded well
      to SCIT treatment after one to 3 years. CONCLUSIONS: Systemic steroid injections
      are still widely used to treat pollen allergy. Specific immunotherapy can greatly
      reduce the need for steroids.

PMID- 22984788
TI  - Distinguishing ordinal and disordinal interactions.
AB  - Re-parameterized regression models may enable tests of crucial theoretical
      predictions involving interactive effects of predictors that cannot be tested
      directly using standard approaches. First, we present a re-parameterized
      regression model for the Linear * Linear interaction of 2 quantitative predictors
      that yields point and interval estimates of 1 key parameter-the crossover point
      of predicted values-and leaves certain other parameters unchanged. We explain how
      resulting parameter estimates provide direct evidence for distinguishing ordinal
      from disordinal interactions. We generalize the re-parameterized model to Linear
      * Qualitative interactions, where the qualitative variable may have 2 or 3
      categories, and then describe how to modify the re-parameterized model to test
      moderating effects. To illustrate our new approach, we fit alternate models to
      social skills data on 438 participants in the National Institute of Child Health
      and Human Development Study of Early Child Care. The re-parameterized regression
      model had point and interval estimates of the crossover point that fell near the
      mean on the continuous environment measure. The disordinal form of the
      interaction supported 1 theoretical model-differential-susceptibility-over a
      competing model that predicted an ordinal interaction.

PMID- 22984789
TI  - Structural equation model trees.
AB  - In the behavioral and social sciences, structural equation models (SEMs) have
      become widely accepted as a modeling tool for the relation between latent and
      observed variables. SEMs can be seen as a unification of several multivariate
      analysis techniques. SEM Trees combine the strengths of SEMs and the decision
      tree paradigm by building tree structures that separate a data set recursively
      into subsets with significantly different parameter estimates in a SEM. SEM Trees
      provide means for finding covariates and covariate interactions that predict
      differences in structural parameters in observed as well as in latent space and
      facilitate theory-guided exploration of empirical data. We describe the
      methodology, discuss theoretical and practical implications, and demonstrate
      applications to a factor model and a linear growth curve model.

PMID- 22984791
TI  - Trends in overweight and obesity in Lebanon: evidence from two national cross
      sectional surveys (1997 and 2009).
AB  - BACKGROUND: Even though the obesity epidemic continues to grow in various parts
      of the world, recent reports have highlighted disparities in obesity trends
      across countries. There is little empirical evidence on the development and
      growth of obesity in Lebanon and other countries of the Eastern Mediterranean
      Region. Acknowledging the need for effective obesity preventive measures and for
      accurate assessment of trends in the obesity epidemic, this study aims at
      examining and analyzing secular trends in the prevalence of overweight and
      obesity over a 12-year period in Lebanon. METHODS: Based on weight and height
      measurements obtained from two national cross-sectional surveys conducted in 1997
      and 2009 on subjects 6 years of age and older, BMI was calculated and the
      prevalence of obesity was determined based on BMI for adults and BMI z-scores for
      children and adolescents, according to WHO criteria. Age -and sex- adjusted odds
      ratios for overweight and obesity were determined, with the 1997 year as the
      referent category. Annual rates of change in obesity prevalence per sex and age
      group were also calculated. RESULTS: The study samples included a total of 2004
      subjects in the 1997 survey and 3636 in the 2009 survey. Compared to 1997, mean
      BMI values were significantly higher in 2009 among all age and sex groups, except
      for 6-9 year old children. Whereas the prevalence of overweight appeared stable
      over the study period in both 6-19 year old subjects (20.0% vs. 21.2%) and adults
      aged 20 years and above (37.0% vs. 36.8%), the prevalence of obesity increased
      significantly (7.3% vs. 10.9% in 6-19 year olds; 17.4% vs. 28.2% in adults), with
      the odds of obesity being 2 times higher in 2009 compared to 1997, in both age
      groups (OR = 1.96, 95% CI:1.29-2.97 and OR = 2.01, 95% CI: 1.67-2.43,
      respectively). The annual rates of change in obesity prevalence ranged between
      +4.1% in children and adolescents and +5.2% in adults. CONCLUSION: The study's
      findings highlight an alarming increase in obesity prevalence in the Lebanese
      population, over the 12-year study period, and alert to the importance of
      formulating policies and nutritional strategies to curb the obesity rise in the
      country.

PMID- 22984790
TI  - Characteristics of the population eligible for and receiving publicly funded
      bariatric surgery in Canada.
AB  - BACKGROUND: Bariatric surgery is the most effective current treatment for severe
      obesity. Capacity to perform surgery within Canada's public health system is
      limited and potential candidates face protracted wait times. A better
      understanding of the gaps between demand for surgery and the capacity to provide
      it is required. The purpose of this study was to quantify and characterize the
      bariatric surgery-eligible population in Canada in comparison to surgery
      ineligible subjects and surgical recipients. METHODS: Data from adult (age > 20)
      respondents of the 2007-09 nationally representative Canadian Health Measures
      Survey (CHMS) were analyzed to estimate the prevalence and characteristics of the
      surgery-eligible and ineligible populations. Federally mandated administrative
      healthcare data (2007-08) were used to characterize surgical recipients. RESULTS:
      In 2007-09, an estimated 1.5 million obese Canadian adults met eligibility
      criteria for bariatric surgery. 19.2 million were surgery-ineligible (3.4 million
      obese and 15.8 million non-obese). Surgery-eligible Canadians had a mean BMI of
      40.1 kg/m2 (95% CI 39.3 to 40.9 kg/m2) and, compared to the surgery-ineligible
      obese population, were more likely to be female (62 vs. 44%), 40-59 years old (55
      vs. 48%), less educated (43 vs. 35%), in the lowest socioeconomic tertile (41 vs.
      34%), and inactive (73 vs. 59%). Self-rated mental health and quality of life
      were lower and comorbidity was higher in surgery-eligible respondents compared
      with the ineligible populations. The annual proportion of Canadians eligible for
      surgery that actually underwent a publicly funded bariatric surgery between 2007
      09 was 0.1%. Surgical recipients (n = 847) had a mean age of 43.6 years (SD 11.1)
      and 82% were female. With the exception of type 2 diabetes, obesity-related
      comorbidity prevalence was much lower in surgical recipients compared to those
      eligible for surgery. CONCLUSIONS: The proportion of bariatric surgery-eligible
      Canadians that undergo publicly funded bariatric surgery is very low. There are
      notable differences in sociodemographic profiles and prevalence of comorbidities
      between surgery-eligible subjects and surgical recipients.

PMID- 22984792
TI  - Arterial supply of the tendinous rotator cuff insertions: an anatomical study.
AB  - BACKGROUND: Confirming the presence of arteries crossing the osteotendinous
      junctions (OTJs) of the rotator cuff may explain why rates of avascular necrosis
      (AVN) of the humeral head vary between three- and four-part proximal humeral
      fractures. It is hypothesized that the humeral head remains better vascularized
      in three-part fractures because one tuberosity with its inserting rotator cuff
      tendons is still attached to the articular fragment and supplying it with blood.
      METHODS: Eighty rotator cuff tendons from 20 shoulder girdles of cadavers aged 68
      94 years were studied. In six shoulder girdles, the anterior circumflex humeral
      artery and posterior circumflex humeral artery (PCHA) were injected with ink, and
      the extra- and intraosseous courses of the vasculature were dissected until the
      OTJs of the rotator cuff. RESULTS: The rotator cuff insertions received an
      arterial supply across their OTJs in 50% of cases (75% in supraspinatus, 67% in
      subscapularis, 33% in infraspinatus and 20% in teres minor). Supraspinatus and
      subscapularis insertions were vascularized by the arcuate artery, while the
      insertions of infraspinatus and teres minor were supplied by an unnamed terminal
      branch of the PCHA. This was named 'posterolateral artery'. CONCLUSION: The
      presence of arteries crossing the OTJs of the rotator cuff, as well as the
      differences in the frequency arteries crossed the OTJs of individual rotator cuff
      tendons, may help explain why there is a lower rate of AVN of the humeral head in
      thee-part, compared with four-part proximal humeral fractures.

PMID- 22984793
TI  - Behavior matching in multimodal communication is synchronized.
AB  - A variety of theoretical frameworks predict the resemblance of behaviors between
      two people engaged in communication, in the form of coordination, mimicry, or
      alignment. However, little is known about the time course of the behavior
      matching, even though there is evidence that dyads synchronize oscillatory
      motions (e.g., postural sway). This study examined the temporal structure of
      nonoscillatory actions-language, facial, and gestural behaviors-produced during a
      route communication task. The focus was the temporal relationship between
      matching behaviors in the interlocutors (e.g., facial behavior in one
      interlocutor vs. the same facial behavior in the other interlocutor). Cross
      recurrence analysis revealed that within each category tested (language, facial,
      gestural), interlocutors synchronized matching behaviors, at temporal lags short
      enough to provide imitation of one interlocutor by the other, from one
      conversational turn to the next. Both social and cognitive variables predicted
      the degree of temporal organization. These findings suggest that the temporal
      structure of matching behaviors provides low-level and low-cost resources for
      human interaction.

PMID- 22984795
TI  - Obesity and asthma in Caucasian preschool children: is there a gender difference?

PMID- 22984796
TI  - Information for clinicians: commercially available molecular diagnosis testing in
      the evaluation of thyroid nodule fine-needle aspiration specimens.
AB  - TSH receptor mRNA reverse transcription-polymerase chain reaction, the Veracyte
      and Asuragen commercial methods, and the noncommercial use of BRAF, RAS, RET/PTC,
      and PAX8/PPARgamma testing have promising roles in the diagnosis and treatment of
      patients with nodular thyroid disease and thyroid cancer. However, at this time,
      experience with these molecular methods remains limited, and no test has perfect
      sensitivity and specificity. Peer-reviewed data evaluating the diagnostic
      performance of these tests are increasingly available. The American Thyroid
      Association (ATA) feels that until an expert consensus review of existing data
      (now underway by the ATA Guidelines Task Force) can be completed, no evidence
      based recommendation for or against the use of these methods can be made.
      Clinicians are therefore advised to consider the use of these genetic diagnosis
      methods with appropriate caution, and to remain cognizant of the limitations of
      the data supporting their use. Patients who are interested in the use of these
      tests in their own care should discuss them thoroughly with their care providers.
      Until evidence-based recommendations are available, determining whether or not
      the limited data available support the use of these methods should be considered
      on a case-by-case basis.

PMID- 22984794
TI  - Review: interventions to increase influenza vaccination among healthcare workers
      in hospitals.
AB  - Annual influenza vaccination rates among hospital healthcare workers (HCW) are
      almost universally low despite recommendations from WHO and public health
      authorities in many countries. To assist in the development of successful
      vaccination programmes, we reviewed studies where interventions aimed to increase
      the uptake of influenza vaccination among hospital HCW. We searched PUBMED from
      1990 up to December 2011 for publications with predetermined search strategies
      and of pre-defined criteria for inclusion or exclusion. We evaluated a large
      number of 'intervention programmes' each employing one or more 'intervention
      components' or strategies, such as easy access to vaccine or educational
      activities, with the goal to raise influenza vaccine uptake rates in hospital HCW
      during one influenza season. Included studies reported results of intervention
      programmes and compared the uptake with the season prior to the intervention
      (historical control) or to another intervention programme within the same season
      that started from the same set of baseline activities. Twenty-five studies
      performed in eight countries met our selection criteria and described 45 distinct
      intervention programmes. Most studies used their own facility as historical
      control and evaluated only one season. The following elements were used in
      intervention programmes that increased vaccine uptake: provision of free vaccine,
      easy access to the vaccine (e.g. through mobile carts or on-site vaccination),
      knowledge and behaviour modification through educational activities and/or
      reminders and/or incentives, management or organizational changes, such as the
      assignment of personnel dedicated to the intervention programme, long-term
      implementation of the strategy, requiring active declination and mandatory
      immunization policies. The number of these components applied appeared to be
      proportional to the increase in uptake. If influenza uptake in hospital HCW is to
      be increased on sustained basis, hospital managers need to be committed to
      conduct a well-designed long-term intervention programme that includes a variety
      of co-ordinated managerial and organizational elements.

PMID- 22984797
TI  - Mediating effects of processing speed and executive functions in age-related
      differences in episodic memory performance: a cross-validation study.
AB  - OBJECTIVE: Age differences in episodic memory (memory) have been attributed to a
      general reduction in processing speed (the "speed mediation hypothesis"), but
      also to declines in the efficiency of executive functions operations ("executive
      decline hypothesis"). To test predictions from these competing models, we
      examined the mediating effects of processing speed (speed) and executive
      functions (executive) on age and episodic memory in three older adult cohorts.
      METHOD: The first sample comprised 842 individuals from the Sydney Memory and
      Aging Study (MAS). The second and third samples included 476 individuals from the
      Older Australian Twins Study (OATS), with each twin from a pair randomly assigned
      to form two samples. A series of regression analyses was performed on each of the
      three samples independently, so as to obtain the sizes and statistical
      significances of the indirect effects of age on each of the memory variables,
      mediated by each of the Executive and Speed composites. Sex was a control
      variable for all analyses. Analyses were repeated with current depression as an
      additional control variable. RESULTS: Data from the MAS sample suggested that
      both Speed and Executive composites were significant mediators, with the former
      having a stronger mediation effect. A similar pattern was found in the two OATS
      samples. CONCLUSIONS: These findings are consistent with those of previous
      studies in which speed had a stronger mediating effect than executive on age
      related variation in memory. They provide further support for the speed mediation
      hypothesis, although not negating the executive decline hypothesis.

PMID- 22984799
TI  - Sleep quality and cognitive function in healthy old age: the moderating role of
      subclinical depression.
AB  - OBJECTIVE: Previous research has yielded inconclusive results on the relationship
      between self-reported sleep quality and cognitive performance in healthy old age.
      Discrepant findings have been reported regarding processing speed and attention,
      executive functions, and episodic memory. However, sleep quality has also been
      found to be related to cognitive performance in patients with depression. Our aim
      was to clarify the relationship between sleep quality and cognitive performance
      in healthy older adults, and to evaluate the moderating role of subclinical
      depression on this relationship. METHOD: The Pittsburgh Sleep Quality Index was
      used to assess subjective sleep quality in 107 participants (age >= 61 years). A
      broad battery of neuropsychological tests measured basic cognitive processes,
      executive functions, and memory processes. RESULTS: Subclinical depression
      moderated the link between sleep quality and cognitive performance. More
      precisely, poorer sleep quality was associated with lower performance in
      reasoning, semantic fluency, and shifting in those with high versus low levels of
      subclinical depression. CONCLUSION: Our findings suggest that poor sleep quality
      might affect higher order cognitive processes, particularly in those reporting
      higher levels of subclinical depression. Findings on the relationships between
      sleep quality, cognitive functioning, and depressive symptomatology are discussed
      in relation to neurobehavioral theories of sleep.

PMID- 22984798
TI  - Facial emotional processing in HIV infection: relation to neurocognitive and
      neuropsychiatric status.
AB  - OBJECTIVE: To examine facial emotional processing in HIV+ individuals and its
      relation to neurocognitive performance, neuropsychiatric symptomatology and
      immune status. METHOD: Participants included 85 HIV+ individuals (83 males, 2
      females) and 25 age-comparable HIV- individuals (22 males, 3 females).
      Participants underwent The University of Pennsylvania computerized
      neuropsychological facial emotion test battery, standardized neuropsychological
      testing, neurobehavioral questionnaires, a semistructured psychiatric interview,
      and an assessment of independence in activities of daily living. RESULTS:
      Relative to HIV- controls, HIV+ individuals showed a mild difference for
      recognition of sadness (p = .02, d = 0.43), discrimination of happiness (p = .02,
      d = 0.52), and speed of recognition for fear (p = .04, d = 0.37). HIV+
      individuals with HIV-associated neurocognitive disorder (HAND; 20%) had abnormal
      emotional facial recognition (p = .04; d = .59), and slower recognition of
      negative facial expressions (p < .01; d = .63-.83), as well as poorer
      discrimination of happy facial expressions (p < .003, d = .83). Apathy,
      depression, reduced independence in activities of daily living, and HIV
      biomarkers were not associated with reduced facial emotion recognition in the
      HIV+ group. CONCLUSIONS: Clinically stable HIV+ individuals show a mild level of
      emotional processing reduction that is dissociated from neuropsychiatric
      complaints. Individuals with HAND showed moderate to large emotional processing
      abnormalities, particularly for the timely recognition of negative expressions
      (fear, sadness, and anger). These findings warrant a more comprehensive and
      dynamic evaluation of emotional processing in HIV infection and an investigation
      of the integrity of the fronto-basal-amygdala circuits.

PMID- 22984800
TI  - The nature and correlates of change in depressive symptoms with cancer diagnosis:
      reaction and adaptation.
AB  - Major life events trigger change processes in mental health. We examined how
      depressive symptoms change in conjunction with cancer diagnosis during adulthood
      and old age, and whether sociodemographic variables, cognitive and health
      resources, and cancer-specific mortality risks moderate event-related reaction
      and adaptation. Specifically, we applied multiphase growth models to prospective
      longitudinal data from 2,848 participants (age at diagnosis: M = 69, SD = 9.91;
      46% women) in the Health and Retirement Study (HRS) who reported receiving a
      cancer diagnosis while enrolled in the study. On average, individuals experienced
      a significant increase in depressive symptoms within 2 years of cancer diagnosis,
      still-elevated levels 2 years postdiagnosis, and smaller increases in depressive
      symptoms postdiagnosis relative to the increases observed prediagnosis. Better
      memory and lower cancer-specific mortality risks were protective against
      increases in depressive symptoms within 2 years of diagnosis and were associated
      with reporting fewer depressive symptoms 2 years postdiagnosis. Findings suggest
      that diagnosis-related changes in depressive symptoms are typically characterized
      by a multiphase pattern, but tremendous between-person differences also emerged
      within each phase. Follow-up analyses comparing a matched group (N = 2,272) who
      did not experience cancer provided an additional layer of evidence supporting our
      inferences. Results indicate that, on average, people adapt and adjust to the
      challenges accompanying a cancer diagnosis, and illustrate the utility of using
      natural experiments such as major life events as a paradigm for studying
      developmental change processes.

PMID- 22984801
TI  - Thermodynamic versus conformational metastability in fibril-forming lysozyme
      solutions.
AB  - The role of intermolecular interaction in fibril-forming protein solutions and
      its relation with molecular conformation is a crucial aspect for the control and
      inhibition of amyloid structures. Here, we study the fibril formation and the
      protein-protein interactions of lysozyme at acidic pH and low ionic strength. The
      amyloid formation occurs after a long lag time and is preceded by the formation
      of oligomers, which seems to be off-pathway with respect to fibrillation. By
      measuring the osmotic isothermal compressibility and the collective diffusion
      coefficient of lysozyme in solution, we observe that the monomeric solution is
      kept in a thermodynamically metastable state by strong electrostatic repulsion,
      even in denaturing conditions. The measured repulsive interaction between
      monomers is satisfactorily accounted for by classical polyelectrolyte theory.
      Further, we observe a slow conformational change involving both secondary and
      tertiary structure, which drives the proteins toward a more hydrophobic
      conformation. Denatured proteins are driven out of metastability through
      conformational substates, which are kinetically populated and experience a lower
      activation energy for fibril formation. Thus, our results highlight the role of
      electrostatic repulsion, which hinders the aggregation of partially denatured
      proteins and operates as a gatekeeper favoring the association of those monomers
      whose conformation is capable of forming amyloid structure.

PMID- 22984802
TI  - Multigroup confirmatory factor analysis of U.S. and Italian children's
      performance on the PASS theory of intelligence as measured by the Cognitive
      Assessment System.
AB  - This study examined Italian and U.S. children's performance on the English and
      Italian versions, respectively, of the Cognitive Assessment System (CAS; Naglieri
      & Conway, 2009; Naglieri & Das, 1997), a test based on a neurocognitive theory of
      intelligence entitled PASS (Planning, Attention, Simultaneous, and Successive;
      Naglieri & Das, 1997; Naglieri & Otero, 2011). CAS subtest, PASS scales, and Full
      Scale scores for Italian (N=809) and U.S. (N=1,174) samples, matched by age and
      gender, were examined. Multigroup confirmatory factor analysis results supported
      the configural invariance of the CAS factor structure between Italians and
      Americans for the 5- to 7-year-old (root-mean-square error of approximation
      [RMSEA]=.038; 90% confidence interval [CI]=.033, .043; comparative fit index
      [CFI]=.96) and 8- to 18-year-old (RMSEA=.036; 90% CI=.028, .043; CFI=.97) age
      groups. The Full Scale standard scores (using the U.S. norms) for the Italian
      (100.9) and U.S. (100.5) samples were nearly identical. The scores between the
      samples for the PASS scales were very similar, except for the Attention Scale
      (d=0.26), where the Italian sample's mean score was slightly higher. Negligible
      mean differences were found for 9 of the 13 subtest scores, 3 showed small d
      ratios (2 in favor of the Italian sample), and 1 was large (in favor of the U.S.
      sample), but some differences in subtest variances were found. These findings
      suggest that the PASS theory, as measured by CAS, yields similar mean scores and
      showed factorial invariance for these samples of Italian and American children,
      who differ on cultural and linguistic characteristics.

PMID- 22984803
TI  - A taxometric exploration of the latent structure of hoarding.
AB  - Despite controversy regarding the classification and diagnostic status of
      hoarding disorder, there remains a paucity of research on the nosology of
      hoarding that is likely to inform the classification debate. The present
      investigation examined the latent structure of hoarding in three, large
      independent samples. Data for three well-validated measures of hoarding were
      subjected to taxometric procedures, including MAXimum EIGenvalue, Mean Above
      Minus Below A Cut, and Latent-Mode factor. Two symptom measures, one of which
      closely mirrors the proposed diagnostic criteria for hoarding disorder, and a
      measure of hoarding beliefs were analyzed. Sample 1 (n=2,501) was representative
      of the general German population, while Samples 2 (n=1,149) and 3 (n=500)
      consisted of unselected undergraduate students. Findings across all three samples
      and taxometric procedures provided converging evidence that hoarding is best
      conceptualized as a dimensional construct, present in varying degrees in all
      individuals. Results have implications across research and treatment domains,
      particularly with respect to assessment approaches, treatment response
      determination, and policy decisions. These findings underscore the need for
      further investigations on the nosology of hoarding, to help validate this
      construct as we move forward with respect to our research and treatment efforts,
      as well as the potential inclusion of hoarding disorder in the Diagnostic and
      Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric
      Association, 2012).

PMID- 22984804
TI  - Performance of healthy participants on the Iowa Gambling Task.
AB  - The Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994) is
      often used to assess decision-making deficits in clinical populations. The
      interpretation of the results hinges on 3 key assumptions: (a) healthy
      participants learn to prefer the good options over the bad options; (b) healthy
      participants show homogeneous choice behavior; and (c) healthy participants first
      explore the different options and then exploit the most profitable ones. Here we
      test these assumptions using 2 extensive literature reviews and analysis of 8
      data sets. The results show that all 3 assumptions may be invalid; that is, (a)
      healthy participants often prefer decks with infrequent losses; (b) healthy
      participants show idiosyncratic choice behavior; and (c) healthy participants do
      not show a systematic decrease in the number of switches across trials. Our
      findings question the prevailing interpretation of IGT data and suggest that, in
      future applications of the IGT, key assumptions about performance of healthy
      participants warrant close scrutiny.

PMID- 22984805
TI  - 1H-ENDOR evidence for a hydrogen-bonding interaction that modulates the
      reactivity of a nonheme Fe(IV)?O unit.
AB  - We report that a novel use of 35 GHz (1)H-ENDOR spectroscopy establishes the
      presence in 1 of an Fe(IV)?O...H-O-Fe(III) hydrogen bond predicted by density
      functional theory computations to generate a six-membered-ring core for 1. The
      hydrogen bond rationalizes the difference in the C-H bond cleavage reactivity
      between 1 and 4(OCH(3)) (where a CH(3)O group has replaced the HO on the Fe(III)
      site). This result substantiates the seemingly paradoxical conclusion that the
      nonheme Fe(IV)?O unit of 1 not only has the electrophilic character required for
      H-atom abstraction but also retains sufficient nucleophilic character to accept a
      hydrogen bond from the Fe(III)-OH unit.

PMID- 22984806
TI  - Discovery and characterization of NK13650s, naturally occurring p300-selective
      histone acetyltransferase inhibitors.
AB  - The histone acetyltransferase (HAT) activity of p300 is essential for androgen
      receptor (AR) function. Androgen-independent prostate cancer cells require AR
      mediated transcriptional activation for their growth. These observations indicate
      that p300 HAT is a promising target to overcome such hormone-resistant cancer
      cells. We sought p300 HAT inhibitors among microbial metabolites. By culturing a
      production strain belonging to Penicillium, we identified two new compounds,
      NK13650A and NK13650B, which were obtained as specific p300 HAT inhibitors.
      Structural analyses of these compounds elucidated that NK13650s have novel
      chemical structures comprising several amino acids and citrate. We applied a
      newly developed biosynthesis-based method to reveal the absolute configuration at
      the citrate quaternary carbon. This was accomplished by feeding a (13)C-labeled
      biosynthetic precursor of citrate. NK13650s selectively inhibited the activity of
      p300 HAT but not that of Tip60 HAT. NK13650s showed inhibitory activity against
      agonist-induced AR transcriptional activation, and NK13650A treatment inhibited
      hormone-dependent and -independent growth of prostate cancer cells.

PMID- 22984808
TI  - Determination of the quantum dot band gap dependence on particle size from
      optical absorbance and transmission electron microscopy measurements.
AB  - This work addresses the determination of arbitrarily shaped particle size
      distributions (PSDs) from PbS and PbSe quantum dot (QD) optical absorbance
      spectra in order to arrive at a relationship between band gap energy and particle
      size over a large size range. Using a modified algorithm which was previously
      developed for ZnO, we take only bulk absorption data from the literature and
      match the PSDs derived from QD absorbance spectra with those from transmission
      electron microscopical (TEM) image analysis in order to arrive at the functional
      dependence of the band gap on particle size. Additional samples sized solely from
      their absorbance spectra with our algorithm show excellent agreement with TEM
      results. We investigate the influence of parameters of the TEM image analysis
      such as threshold value on the final result. The band gap versus size
      relationship developed from analysis of just two samples lies well within the
      bounds of a number of published data sets. We believe that our methodology
      provides an attractive shortcut for the study of various novel quantum-confined
      direct band gap semiconductor systems as it permits the band gap energies of a
      broad size range of QDs to be probed with relatively few synthetic experiments
      and without quantum mechanical simulations.

PMID- 22984807
TI  - Natural product disaccharide engineering through tandem glycosyltransferase
      catalysis reversibility and neoglycosylation.
AB  - A two-step strategy for disaccharide modulation using vancomycin as a model is
      reported. The strategy relies upon a glycosyltransferase-catalyzed 'reverse'
      reaction to enable the facile attachment of an alkoxyamine-bearing sugar to the
      vancomycin core. Neoglycosylation of the corresponding aglycon led to a novel set
      of vancomycin 1,6-disaccharide variants. While the in vitro antibacterial
      properties of corresponding vancomycin 1,6-disaccharide analogs were equipotent
      to the parent antibiotic, the chemoenzymatic method presented is expected to be
      broadly applicable.

PMID- 22984809
TI  - Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and
      design of isosteres yielding orally available cathepsin K inhibitors.
AB  - Rational structure-based design has yielded highly potent inhibitors of cathepsin
      K (Cat K) with excellent physical properties, selectivity profiles, and
      pharmacokinetics. Compounds with a 3,4-(CH3O)2Ph motif, such as 31, were found to
      have excellent metabolic stability and absorption profiles. Through metabolite
      identification studies, a reactive metabolite risk was identified with this
      motif. Subsequent structure-based design of isoteres culminated in the discovery
      of an optimized and balanced inhibitor (indazole, 38).

PMID- 22984810
TI  - Folate receptor in adenocarcinoma and squamous cell carcinoma of the lung:
      potential target for folate-linked therapeutic agents.
AB  - CONTEXT: Lung cancer is the number one cause of cancer deaths in the United
      States and globally. The advent of targeted therapies has offered a new treatment
      paradigm for lung cancer, but currently validated and emerging drugs are
      effective in only a small minority of lung cancers, predominantly
      adenocarcinomas. Folate receptors can serve as targets for drugs attached to
      folate and are overexpressed in many cancers. OBJECTIVE: To determine the
      frequency of folate receptor overexpression in lung cancers of different cell
      types as potential targets for folate-linked therapy. DESIGN: High-density tissue
      microarrays were constructed from archival formalin-fixed, paraffin-embedded
      resection specimens from 188 primary stage I or stage II adenocarcinomas or
      squamous cell carcinomas of the lung with three 0.1-cm cores from each tumor.
      Tissue microarrays were immunostained for folate receptor alpha with mAb343 and
      the results scored (0 to 1+ = weak expression, 2+ to 3+ = strong expression).
      RESULTS: Eighty-four of 117 (72%) of the adenocarcinomas were strongly positive
      for the folate receptor, and 36 of 71 (51%) of the squamous cell carcinomas were
      strongly positive for the folate receptor. CONCLUSIONS: Our data indicate that a
      large percentage of lung cancers, including squamous cell carcinomas in addition
      to adenocarcinomas, strongly express folate receptor. This suggests that folate
      linked targeted therapy can potentially be used to treat the majority of lung
      cancers, both adenocarcinomas and, particularly, squamous cell carcinomas, that
      do not respond to current targeted therapies.

PMID- 22984812
TI  - Isolation of Bacillus anthracis from soil in selected high-risk areas of
      Zimbabwe.
AB  - AIMS: To isolate Bacillus anthracis from cattle carcass burial sites from high
      risk districts in Zimbabwe. METHODS AND RESULTS: Soil samples were collected from
      carcass burial sites from seven areas, including two national game parks. Samples
      were collected from top 5-10 cm, and for spore extraction, 25 g of soil was
      suspended in sterile distilled water overnight. Supernatants were filtered
      through 0.45-MUm pore cellulose nitrate, deposits suspended in 5 ml phosphate
      buffered saline, aliquoted and heated at temperature regimen of 65, 70, 75 and 80
      degrees C for 15 min. Samples were plated onto PLET agar. B. anthracis isolates
      were identified using growth morphology and PCR detecting pXO1 and pXO2 virulence
      plasmids. From samples heated at 75  degrees C for 15 min, B. anthracis were
      isolated from 9 of 81 (11.1%) soil samples representing five of the seven sampled
      areas. CONCLUSIONS: We isolated B. anthracis from soil collected from carcass
      burial sites. PCR targeting virulence plasmids provided a rapid confirmation of
      B. anthracis. SIGNIFICANCE AND IMPACT OF THE STUDY: The positive isolation
      indicated that some carcass burial sites may retain viable spores for at least 12
      months after the previous outbreak, which suggests that they may be important
      sources of B. anthracis and new disease outbreaks.

PMID- 22984813
TI  - Ethidium bromide-adsorbed graphene templates as a platform for preferential
      sensing of DNA.
AB  - Sulfonated graphene (SG) and graphene oxide (GO) are used as an ethidium bromide
      (EtBr, E) binding platform, to preferentially sense DNA (D) among the other
      biomolecules such as RNA (R), bovine serum albumin (BSA, P) and glucose (G) using
      spectroscopic techniques. EtBr loses its intrinsic fluorescence property after
      binding with SG. DNA can "turn on" the quenched fluorescence of an SG-EtBr hybrid
      to a greater extent compared to the RNA, BSA, and glucose. UV-vis absorption
      spectra and circular dichroism (CD) spectra also support the higher ability of
      DNA to release adsorbed EtBr from the SG surface in comparison to the above
      mentioned biomolecules. Compared to GO-EtBr, the SG-EtBr hybrid is superior to
      preferentially sense DNA, as the enhancement of fluorescence intensity is 16
      times in the later but it is 4.5 times in the former from their respective
      complexes. An analysis of Raman spectral data indicates that the interaction of
      EtBr in its adsorbed state on an SG template is greater with DNA than with RNA.

PMID- 22984815
TI  - Does the presence of anterior mandibular teeth increase the incidence of denture
      stomatitis?
AB  - PURPOSE: To compare the frequency of denture stomatitis (DS) under maxillary
      complete dentures (CDs) in patients with opposing mandibular distal extension
      removable partial dentures (RPDs) and CDs. MATERIALS AND METHODS: Participants
      included 365 maxillary CD wearers (241 women, mean age 70.5 +/- 13.2 years; 124
      men, mean age 71.5 +/- 10.4 years) from 7 rest homes in Istanbul. A total of 268
      had mandibular CDs; 97 had mandibular distal extension RPDs. Two independent,
      calibrated examiners performed oral examinations. Presence of maxillary denture
      related stomatitis and the effect of risk factors on DS were evaluated and
      recorded. RESULTS: The frequency of palatal DS (Newton I-III) was 45.1% (n = 121)
      in the mandibular CD group and 49.5% (n = 48) in the mandibular distal extension
      RPD group, a statistically insignificant difference (p= 0.4). Factors
      significantly associated with palatal DS were maxillary denture age (p= 0.02),
      reduced occlusal vertical dimension (p= 0.04), and nocturnal denture wear (p=
      0.03). CONCLUSION: In this study, DS beneath maxillary CDs did not differ between
      mandibular distal extension RPD and CD wearers. The presence of mandibular
      anterior teeth did not influence the occurrence of palatal DS.

PMID- 22984814
TI  - Cytochrome P450s and cytochrome P450 reductase in the olfactory organ of the
      cotton leafworm Spodoptera littoralis.
AB  - Cytochrome P450 enzymes (P450s) are involved in many physiological functions in
      insects, such as the metabolism of signal molecules, adaptation to host plants
      and insecticide resistance. Several P450s have been reported in the olfactory
      organs of insects, the antennae, and have been proposed to play a role in odorant
      processing and/or xenobiotic metabolism. Despite recent transcriptomic analyses
      in several species, the diversity of antennal P450s in insects has not yet been
      investigated. Here, we report the identification of 37 putative P450s expressed
      in the antennae of the pest moth Spodoptera littoralis, as well as the
      characterization of a redox partner, cytochrome P450 reductase (CPR).
      Phylogenetic analysis revealed that S. littoralis P450s belong to four clades
      defined by their conservation with vertebrate P450s and their cellular
      localization. Interestingly, the CYP3 and CYP4 clans, which have been described
      to be mainly involved in the metabolism of plant compounds and xenobiotics, were
      largely predominant. More surprisingly, two P450s related to ecdysteroid
      metabolism were also identified. Expression patterns in adult and larval tissues
      were studied. Eight P450s appeared to be specific to the chemosensory organs, ie
      the antennae and proboscis, suggesting a specific role in odorant and tastant
      processing. Moreover, exposure of males to a plant odorant down-regulated the
      transcript level of CPR, revealing for the first time the regulation of this gene
      by odorants within insect antennae. This work suggests that the antennae of
      insects are a key site for P450-mediated metabolism of a large range of exogenous
      and endogenous molecules.

PMID- 22984816
TI  - The evaluation of fungal endophyte toxin residues in milk.
AB  - AIM: To determine the concentrations of fungal endophyte toxins in the milk of
      cows fed perennial ryegrass containing wild-type or AR37 endophyte. METHODS:
      Groups of 10 multiparous Holstein-Friesian cows were fed wild-type (containing
      lolitrem B) or AR37 (containing epoxy-janthitrems) endophyte-infected perennial
      ryegrass (Lolium perenneL.). Animals were kept indoors and fed for 12 days. Over
      this period, animals were regularly assessed for ryegrass staggers and herbage
      intake measured. At the conclusion of the 12-day indoor-feeding period, cows were
      grazed on AR1 (toxin-free) pastures for a further 8 days. Daily individual milk
      samples and milk yields were collected over the complete 20-day period. Milk
      samples were analysed for endophyte toxins using HPLC methods developed during
      this study. Daily herbage samples were also taken and concentrations of endophyte
      toxins measured. RESULTS: Methods were successfully developed for the analysis of
      lolitrem B and epoxy-janthitrems in milk which allowed the concentrations of
      these compounds in milk to be compared with the concentrations in feed consumed
      by the animals. Both toxin types could be detected in milk after only 1 day of
      exposure to respective treatment pastures. The maximum concentration of endophyte
      toxins in milk was 5 ng/mL lolitrem B and 109 ng/mL epoxy-janthitrems from cows
      fed wild-type and AR37 endophyte-infected ryegrass pastures, respectively.
      Concentrations of epoxy-janthitrems present in herbage were much higher than for
      lolitrem B (Day 1-12 average of 14.6 and 1.8 ppm, respectively). Despite the high
      concentrations of epoxy-janthitrems consumed by cows fed AR37 endophyte-infected
      pastures no signs of ryegrass staggers were observed over the experimental
      period, whereas those cows fed wild-type endophyte-infected pastures all showed
      signs of ryegrass staggers. This is consistent with the view that epoxy
      janthitrems are low potency tremorgens. At the conclusion of the toxin feeding
      period, endophyte toxin concentrations in milk quickly dropped to almost zero
      after 8 days. A comparison of the quantities of lolitrem B and epoxy-janthitrems
      consumed by each cow with the quantities secreted in milk showed that only very
      low proportions of the total amount ingested are secreted in milk (0.23% lolitrem
      B and 0.49% epoxy-janthitrems). CONCLUSION: Lolitrem B and epoxy-janthitrems can
      be detected in the milk of cows consuming wild-type and AR37 endophyte-infected
      perennial ryegrass, respectively. Concentrations detected were low and changed
      quickly in association with the amounts being consumed by the cows. Available
      evidence gives no indication that these compounds may pose a threat to human
      health.

PMID- 22984817
TI  - Leading during change: the effects of leader behavior on sickness absence in a
      Norwegian health trust.
AB  - BACKGROUND: Organizational change often leads to negative employee outcomes such
      as increased absence. Because change is also often inevitable, it is important to
      know how these negative outcomes could be reduced. This study investigates how
      the line manager's behavior relates to sickness absence in a Norwegian health
      trust during major restructuring. METHODS: Leader behavior was measured by
      questionnaire, where employees assessed their line manager's behavior (N = 1008;
      response rate 40%). Data on sickness absence were provided at department level (N
      = 35) and were measured at two times. Analyses were primarily conducted using
      linear regression; leader behavior was aggregated and weighted by department
      size. RESULTS: The results show a relationship between several leader behaviors
      and sickness absence. The line managers' display of loyalty to their superiors
      was related to higher sickness absence; whereas task monitoring was related to
      lower absence. Social support was related to higher sickness absence. However,
      the effect of social support was no longer significant when the line manager also
      displayed high levels of problem confrontation. CONCLUSIONS: The findings clearly
      support the line manager's importance for employee sickness absence during
      organizational change. We conclude that more awareness concerning the manager's
      role in change processes is needed.

PMID- 22984818
TI  - Prospective, multicentre, randomized controlled trial of bladder filling prior to
      trial of void on the timing of discharge.
AB  - BACKGROUND: The objective of this study was to investigate whether bladder
      filling with saline prior to trial of void (TOV) was safe and whether it reduced
      time to discharge compared with standard TOV in the urology inpatient setting for
      patients post-transurethral resection of prostate, bladder neck incision or an
      admission with urinary retention. METHODS: Prospective, multicentre, randomized
      controlled trial at Hawkes Bay and Waikato hospitals with local ethics committee
      approval. All consecutive, consented patients requiring TOV were randomized into
      filling and control groups. The filling groups were filled with normal saline
      prior to TOV (up to 500 mL or first sensation of fullness). The control group had
      their catheter removed at 06.00 hours without filling. Time taken between
      catheter removal and discharge was recorded in minutes. Complications were
      recorded. RESULTS: Fifty-two patients were recruited and randomized with 27 and
      25 patients in the filling and control groups, respectively. The mean time taken
      from catheter removal to discharge was 300.6 min in the filling group and 340.1
      min in the control group. The filling group reduced the time to discharge by 39.5
      min (P = 0.304). Furthermore, 2/27 and 2/25 patients in the filling and control
      groups, respectively, developed urinary retention after TOV and required re
      catheterization prior to discharge. CONCLUSION: Bladder filling prior to TOV
      showed a non-statistically significant reduction in the time to discharge of 39.5
      min. Despite the fact that bladder filling is a safe and cheap procedure, it
      cannot be recommended for use in an attempt to reduce time to discharge in an
      inpatient setting.

PMID- 22984819
TI  - Granulomatous appendicitis in a child.
AB  - Granulomatous appendicitis (GA) is a rare inflammatory condition affecting the
      appendix. We report a pediatric patient with GA in which symptoms resolved after
      appendectomy. Although the colon was grossly normal by endoscopy, microscopic
      examination revealed colitis without granuloma formation. GA may represent a
      variant of inflammatory bowel disease (IBD).

PMID- 22984820
TI  - Estimating influenza incidence and rates of influenza-like illness in the
      outpatient setting.
AB  - BACKGROUND: Estimating influenza incidence in outpatient settings is challenging.
      We used outpatient healthcare practice populations as a proxy to estimate
      community incidence of influenza-like illness (ILI) and laboratory-confirmed
      influenza-associated ILI. METHODS: From October 2009 to July 2010, 38 outpatient
      practices in seven jurisdictions conducted surveillance for ILI (fever with cough
      or sore throat for patients >= 2 years; fever with >= 1 respiratory symptom for
      patients <2 years). From a sample of patients with ILI, respiratory specimens
      were tested for influenza. RESULTS: During the week of peak influenza activity
      (October 24, 2009), 13% of outpatient visits were for ILI and influenza was
      detected in 72% of specimens. For the 10-month surveillance period, ILI and
      influenza-associated ILI incidence were 20.0 (95% CI: 19.7, 20.4) and 8.7/1000
      (95% CI: 8.2, 9.2) persons, respectively. Influenza-associated ILI incidence was
      highest among children aged 2-17 years. Observed trends were highly correlated
      with national ILI and virologic surveillance. CONCLUSIONS: This is the first
      multistate surveillance system demonstrating the feasibility of using outpatient
      practices to estimate the incidence of medically attended influenza at the
      community level. Surveillance demonstrated the substantial burden of pandemic
      influenza in outpatient settings and especially in children aged 2-17 years.
      Observed trends were consistent with established syndromic and virologic systems.

PMID- 22984821
TI  - Probing ion/molecule interactions in aqueous solutions with vibrational energy
      transfer.
AB  - Interactions between model molecules representing building blocks of proteins and
      the thiocyanate anion, a strong protein denaturant agent, were investigated in
      aqueous solutions with intermolecular vibrational energy exchange methods. It was
      found that thiocyanate anions are able to bind to the charged ammonium groups of
      amino acids in aqueous solutions. The interactions between thiocyanate anions and
      the amide groups were also observed. The binding affinity between the thiocyanate
      anion and the charged amino acid residues is about 20 times larger than that
      between water molecules and the amino acids and about 5-10 times larger than that
      between the thiocyanate anion and the neutral backbone amide groups. The series
      of experiments also demonstrates that the chemical nature, rather than the
      macroscopic dielectric constant, of the ions and molecules plays a critical role
      in ion/molecule interactions in aqueous solutions.

PMID- 22984822
TI  - Social disparities in children's exposure to second hand smoke at home: a
      repeated cross-sectional survey.
AB  - BACKGROUND: Exposure to second hand smoke (SHS) is an important preventable cause
      of morbidity and mortality in children. We hypothesised that there has been a
      growth in social inequality in children's exposure to SHS at home over time. The
      purpose of this study was to investigate temporal change in smoking in homes
      including children, focusing on the socioeconomic differences. METHODS: Data is
      from a repeated cross-sectional survey, 'Health Profiles of the Capital Region of
      Denmark' conducted in 2007 and 2010, in 29 municipalities. The response rate was
      52.3%, in both surveys. Our study included persons aged 25 to 64, living with
      children <=15 years of age; N=9,289 in 2007 and 12,696 in 2010. Analyses were
      weighted for size of municipality and for non-response, which was higher among
      men and among persons who were younger, had a lower income, were living alone,
      were unemployed, and/or were of an ethnicity other than Danish. Regression
      analyses were used to investigate smoking in homes including children across
      parent/adult education levels, focusing on temporal changes. RESULTS: There were
      significant large socioeconomic differences in both 2007 and 2010. In 2010 it was
      more than 11 times more likely for a child to be exposed to SHS at home if the
      parent had very low education than if they were highly educated (p<0.001).
      Smoking in a home with children decreased from 16.2% in 2007 to 10.9% in 2010.
      The odds of a temporal decrease in domestic smoking did not differ significantly
      across parent education levels (p=0.40). CONCLUSIONS: Marked social inequalities
      in children's exposure to SHS and a significant temporal decrease in exposure,
      independent of the education level of the parent/adult, were found in repeated
      large cross-sectional population-based studies. Social disparities have persisted
      over time, but not increased. Both clinical and population policy interventions
      will be needed in order to control child SHS exposure. We call for legislative
      protection of children from tobacco smoke inside their home as a supplement to
      parental education and support for smoking cessation.

PMID- 22984823
TI  - Maternal hypertension and intrapartum fever are associated with increased risk of
      ischemic stroke during infancy.
AB  - AIM: To examine maternal hypertension, diabetes, and intrapartum fever as
      potential risk factors for ischemic stroke in infants. METHOD: We conducted a
      retrospective cohort study of 226,117 children born from January 2000 to December
      2007 who were enrolled in the South Carolina Medicaid program. We linked maternal
      and child Medicaid billing records and birth certificate data. Children with
      ischemic stroke were identified based on the International Classification of
      Diseases, Ninth Revision (ICD-9), code 434 in the child's billing data.
      Independent variables and covariates were identified using ICD-9 codes and birth
      certificate data. We modeled the odds of ischemic stroke diagnosis in infants,
      either before 30 days of life or before 365 days. RESULTS: Forty-three children
      were diagnosed with ischemic stroke before 30 days and 161 before 365 days.
      Maternal hypertension (odds ratio 2.31 before 30 d) and intrapartum fever (odds
      ratio 3.36 <30 d) were significantly associated with odds of ischemic stroke
      before 30 days and before 365 days; maternal diabetes was not. INTERPRETATION:
      Maternal hypertension and intrapartum fever appear to be risk factors for
      ischemic stroke in infants. Additional research is needed to determine the
      mechanism(s) underlying these associations and to develop effective preventive
      methods for high-risk infants.

PMID- 22984824
TI  - Long-term survival after radical surgery for renal cell carcinoma with tumour
      thrombus extension into the right atrium.
AB  - What's known on the subject? and What does the study add? Surgical treatment of
      renal cell carcinoma (RCC) with tumour thrombus extending into the right atrium
      remains, despite its complexity and specific technical aspects, the only radical
      therapeutic option. This single-centre study, unique in size for this rare
      condition, reports early and late results over a period of 18 years. All patients
      were operated on using a standardised protocol with use of cardiopulmonary bypass
      and deep hypothermic circulatory arrest. Overall and cancer-specific cumulative
      survival was better than in other reports. OBJECTIVE: To evaluate the long-term
      results of radical surgical management of renal cell carcinoma (RCC) with tumour
      thrombus extension (TTE) level IV into the right atrium (RCC/TTE IV) in a large
      single-institution series. PATIENTS AND METHODS: Radical complex urological and
      cardio-surgical procedure was performed over a period of 18 years (1993-2010) on
      21 patients with RCC/TTE IV. A radical nephrectomy was performed followed by
      sternotomy, institution of cardiopulmonary bypass and extraction of the
      intracardiac tumour thrombus under direct visual control during deep hypothermic
      circulatory arrest (DHCA). Perioperative and postoperative variables, and long
      term overall and cancer-specific survival using the Kaplan-Meier method were
      analysed. RESULTS: In all patients, precise removal of tumour thrombus was
      accomplished in a bloodless field during DHCA. The mean (sd) duration of
      circulatory arrest was 16 (6) min at a mean hypothermia of 20 (3)  degrees C. In
      hospital mortality was 9.5% (two patients). The median survival (including in
      hospital mortality) was 25 months. In Kaplan-Meier analysis, 2- and 5-year
      overall cumulative survival rate was 57 (95% confidence interval, CI 36-78)% and
      37 (95% CI 15-58)%, respectively. Cancer-specific cumulative survival was 68 (95%
      CI 49-89)% at 2 years and 51 (95% CI 28-74)% at 5 years. CONCLUSIONS: Late
      outcome after radical surgical treatment in patients with RCC and TTE reaching up
      to the right atrium justifies this extensive procedure. Cardiopulmonary bypass
      with DHCA allows safe and precise extirpation of all intracaval and intracardiac
      tumour mass.

PMID- 22984826
TI  - Yeast-mediated xanthone synthesis through oxidative intramolecular cyclization.
AB  - Benzoylphloroglucinol derivatives are natural products showing diverse biological
      activities that could be modulated by structural modifications. For this purpose,
      we studied the biotransformation of guttiferone A and of maclurin using a
      combinatorial approach for screening active microorganism strains. We found a
      novel and unexpected yeast-catalyzed oxidation that has selectively given a new
      oxy-guttiferone A and norathyriol.

PMID- 22984827
TI  - Synthesis, structures, and magnetic behavior of new anionic copper(II) sulfate
      aggregates and chains.
AB  - The reaction between CuSO(4).5H(2)O and [NMe(2)H(2)]Cl in N,N'-dimethylformamide
      (DMF) at 95  degrees C yielded green crystals of
      (NMe(2)H(2))(4)[Cu(6)O(2)(SO(4))(6)(DMF)(4)] 1. The discrete [Cu(6)(MU(4)
      O)(2)(MU(3)-SO(4))(4)(MU(2)-SO(4))(2)(DMF)(4)](4-) anions present in 1 contain
      two edge-sharing Cu(4)(MU(4)-O) tetrahedra, with the copper(II) centers bridged
      by sulfato ligands. These anions are linked into a two-dimensional network
      through hydrogen bonds involving the dimethylammonium cations. When the reaction
      was carried out in the absence of [NMe(2)H(2)]Cl, yellow-green crystals of
      (NMe(2)H(2))(4)[Cu(6)O(2)(SO(4))(6)(DMF)(2)] 2 were obtained. The anions in 2
      contain similar Cu(6)O(2)(SO(4))(6) aggregates to those in 1, though these differ
      in terms of the copper(II) coordination geometries. In addition, the anions in 2
      are linked into chains through bridging sulfato ligands. The Cu(6)O(2)(SO(4))(6)
      aggregates observed in 1 and 2 are related to those present in the rare copper
      sulfate mineral fedotovite, K(2)Cu(3)O(SO(4))(3), and in common with this mineral
      both 1 and 2 decompose in the presence of moisture. The reaction between
      CuSO(4).5H(2)O and [NMe(2)H(2)]Cl in DMF at room temperature gave
      (NMe(2)H(2))[Cu(2)(OH)(SO(4))(2)(H(2)O)(2)] 3, the structure of which contains
      triangular Cu(3)(OH)(SO(4)) units that share vertices to form tapes. Magnetic
      measurements revealed that 1 and 3 are both spin-canting metamagnetic systems.
      Field-induced responses were observed below 5 K, with the critical field
      indicating metamagnetic behavior from antiferromagnetic to ferromagnetic equal to
      110 Oe for both compounds.

PMID- 22984825
TI  - Longitudinal beta regression models for analyzing health-related quality of life
      scores over time.
AB  - BACKGROUND: Health-related quality of life (HRQL) has become an increasingly
      important outcome parameter in clinical trials and epidemiological research. HRQL
      scores are typically bounded at both ends of the scale and often highly skewed.
      Several regression techniques have been proposed to model such data in cross
      sectional studies, however, methods applicable in longitudinal research are less
      well researched. This study examined the use of beta regression models for
      analyzing longitudinal HRQL data using two empirical examples with distributional
      features typically encountered in practice. METHODS: We used SF-6D utility data
      from a German older age cohort study and stroke-specific HRQL data from a
      randomized controlled trial. We described the conceptual differences between
      mixed and marginal beta regression models and compared both models to the
      commonly used linear mixed model in terms of overall fit and predictive accuracy.
      RESULTS: At any measurement time, the beta distribution fitted the SF-6D utility
      data and stroke-specific HRQL data better than the normal distribution. The mixed
      beta model showed better likelihood-based fit statistics than the linear mixed
      model and respected the boundedness of the outcome variable. However, it tended
      to underestimate the true mean at the upper part of the distribution. Adjusted
      group means from marginal beta model and linear mixed model were nearly identical
      but differences could be observed with respect to standard errors. CONCLUSIONS:
      Understanding the conceptual differences between mixed and marginal beta
      regression models is important for their proper use in the analysis of
      longitudinal HRQL data. Beta regression fits the typical distribution of HRQL
      data better than linear mixed models, however, if focus is on estimating group
      mean scores rather than making individual predictions, the two methods might not
      differ substantially.

PMID- 22984828
TI  - Evidence for structural phase transitions induced by the triple phase line shift
      in self-catalyzed GaAs nanowires.
AB  - Self-catalyzed growth of GaAs nanowires are widely ascribed to the vapor-liquid
      solid (VLS) mechanism due to the presence of Ga particles at the nanowire tips.
      Here we report synthesis of self-catalyzed GaAs nanowires by molecular-beam
      epitaxy covering a large growth parameter space. By carefully controlling the Ga
      flux and its ratio with the As flux, GaAs nanowires without Ga particles and
      exhibiting a flat growth front are produced. Using scanning electron microscopy
      and high-resolution transmission electron microscopy, we compare the growth rate
      and structure, especially near the growth front, of the nanowires with and
      without Ga droplets. We find that regardless of whether Ga droplets are present
      on top, the nanowires have a short wurtzite section following the zinc-blende
      bulk structure. The nanowires without Ga droplets are terminated by a thin zinc
      blende cap, while the nanowires with Ga droplets do not have such a cap. The bulk
      zinc-blende phase is attributed to the Ga droplet wetting the sidewall during
      growth, pinning the triple phase line on the sidewall. The zinc
      blend/wurtzite/(zinc-blende) phase transitions at the end of growth are fully
      consistent with the triple phase line shifting up to the growth front due to the
      progressive consumption of the Ga in the droplet by crystallization with As. The
      results imply an identical VLS growth mechanism for both types of GaAs NWs, and
      their intricate structures provide detailed comparison with and specific
      experimental verification of the recently proposed growth mechanism for self
      catalyzed III-V semiconductor nanowires ( Phy. Rev. Lett. 2011 , 106 , 125505 ).
      Using this mechanism as a guideline, we successfully demonstrated controllable
      fabrication of two distinct types of axial superlattice GaAs NWs consisting of
      zinc-blende/defect-section and wurtzite/defect-section units.

PMID- 22984829
TI  - Smartly aligning nanowires by a stretching strategy and their application as
      encoded sensors.
AB  - The nanotechnology world is being more and more attracted toward high aspect
      ratio one-dimensional nanostructures due to their potentials as building blocks
      for electronic/optical devices. Here, we propose a novel method to generate
      nanowire patterns with assistance of superhydrophobic flexible
      polydimethylsiloxane (PDMS) substrates. Micropillar gaps are tunable via a
      stretching process of the PDMS surface; thus, diverse nanowire patterns can be
      formed by stretching the same PDMS surface in various ways. Importantly, square
      nanowire loops with alternative compositions can be generated through a double
      stretching process, showing an advanced methodology in controlling the alignment
      of nanowires. Since alternative fluorescent molecules will be quenched by diverse
      chemical substances, this alternative nanowire loop shows a selective detection
      for diverse target compounds, which greatly improves the application of this
      nanowire patterning approach. Furthermore, such alternative nanowire patterns can
      be transferred from pillar-structured surfaces to flat films, indicating further
      potentials in microcircuits, sensitive sensors, and other organic functional
      nanodevices.

PMID- 22984830
TI  - Experiences and interpersonal consequences of hurt feelings and anger.
AB  - This research compared the experiences and consequences of hurt feelings and
      anger in 3 retrospective studies (Studies 1a, 1b, and 2), a dyadic daily diary
      study (Study 3), and a dyadic behavioral observation study (Study 4). Although
      victims felt both hurt and angry in response to perpetrators' behaviors that
      signaled relational devaluation (Studies 1-4), hurt and anger differed in terms
      of victims' subjective experiences and behaviors, perpetrators' responses, and
      relationship consequences. Hurt was characterized by the experience of
      commitment, dependence, and vulnerability; goals to restore the perpetrator's
      acceptance; and constructive behavior. Moreover, victims' hurt was associated
      with perpetrators evaluating victims and victims' commitment more positively,
      with perpetrators' feelings of guilt and empathy and with perpetrators'
      constructive responses. Hurt also had positive consequences for relationships. In
      contrast, victims' anger was generally independent of commitment and
      characterized by the experience of control, invulnerability, and low dependence;
      goals to change perpetrators' behavior; and victims' destructive behavior.
      Furthermore, victims' anger was associated with perpetrators perceiving victims
      to be less committed and elicited reciprocated anger and destructive behaviors
      from perpetrators. These findings suggest that despite relational devaluation
      being a cause of both hurt and anger, these feelings have distinct social
      functions. Hurt reflects a desire to maintain interpersonal connection and repair
      relationships, which will often successfully elicit repair attempts by
      perpetrators, whereas anger reflects a desire to control others via antagonistic
      destructive behaviors, which exacerbate interpersonal difficulties.

PMID- 22984831
TI  - The salience of social referents: a field experiment on collective norms and
      harassment behavior in a school social network.
AB  - Persistent, widespread harassment in schools can be understood as a product of
      collective school norms that deem harassment, and behavior allowing harassment to
      escalate, as typical and even desirable. Thus, one approach to reducing
      harassment is to change students' perceptions of these collective norms. Theory
      suggests that the public behavior of highly connected and chronically salient
      actors in a group, called social referents, may provide influential cues for
      individuals' perception of collective norms. Using repeated, complete social
      network surveys of a public high school, we demonstrate that changing the public
      behavior of a randomly assigned subset of student social referents changes their
      peers' perceptions of school collective norms and their harassment behavior.
      Social referents exert their influence over peers' perceptions of collective
      norms through the mechanism of everyday social interaction, particularly
      interaction that is frequent and personally motivated, in contrast to interaction
      shaped by institutional channels like shared classes. These findings clarify the
      development of collective social norms: They depend on certain patterns of and
      motivations for social interactions within groups across time, and are not static
      but constantly reshaped and reproduced through these interactions. Understanding
      this process creates opportunities for changing collective norms and behavior.

PMID- 22984832
TI  - Personality development from adolescence to emerging adulthood: linking
      trajectories of ego development to the family context and identity formation.
AB  - This longitudinal study analyzed personality development using an individual
      approach by examining changes in ego development across the transition from
      adolescence to emerging adulthood. Specifically, the study mapped the
      heterogeniety in ego development growth trajectories and linked the different
      trajectories to the family context in adolescence and identity development in
      emerging adulthood. Participants were 98 families with a child who were followed
      from age 14 to age 24. Latent class growth analysis identified 4 distinct
      trajectories of growth in ego development of the children over the 10-year
      period. The results indicated that growth was more rapid during adolescence and
      tended to taper off in emerging adulthood. In addition, promotion of personal
      growth within the family and parents' ego development were particulary
      instrumental in children's ego developmental gains in adolescence. Finally, youth
      who demonstrated continued ego development into emerging adulthood also
      demonstrated heightened levels of identity exploration.

PMID- 22984833
TI  - State panel estimates of the effects of the minimum legal drinking age on alcohol
      consumption for 1950 to 2002.
AB  - BACKGROUND: Despite strong evidence supporting the effectiveness of the minimum
      legal drinking age (MLDA), recent movements have attempted to evoke policy
      changes that will allow 18- to 20-year-olds to buy and drink alcohol legally. The
      primary aim of this study was to evaluate the effects of both raising and
      lowering the MLDA on per capita ethanol (EtOH) consumption in longer and more
      accurate time series panel than any previous study. METHODS: Generalized least
      squares model specifications controlling for income, unemployment rates, and
      population characteristics were implemented using MLDA and aggregate EtOH
      consumption data from U.S. states from 1950 to 2002. RESULTS: Results from the
      full 1950 to 2002 period, which include both the lowering and raising of the
      MLDA, show that an increase in the MLDA by 3 years was associated with decreases
      in per capita total EtOH consumption (1.51% reduction), as well as in beer (2.31%
      reduction) and spirits consumption (1.86% reduction). CONCLUSIONS: Lowering the
      MLDA would likely induce increased rates of drinking and subsequent alcohol
      related consequences. If increased consumption is of concern, policymakers should
      resist movements to lower the MLDA.

PMID- 22984834
TI  - Clarithromycin in treatment of acute asthma exacerbations: principles of
      appropriate antibiotic use.

PMID- 22984835
TI  - Identification of high-affinity P2Y12 antagonists based on a phenylpyrazole
      glutamic acid piperazine backbone.
AB  - A series of novel, highly potent P2Y12 antagonists as inhibitors of platelet
      aggregation based on a phenylpyrazole glutamic acid piperazine backbone is
      described. Exploration of the structural requirements of the substituents by
      probing the structure-activity relationship along this backbone led to the
      discovery of the N-acetyl-(S)-proline cyclobutyl amide moiety as a highly
      privileged motif. Combining the most favorable substituents led to remarkably
      potent P2Y12 antagonists displaying not only low nanomolar binding affinity to
      the P2Y12 receptor but also a low nanomolar inhibition of platelet aggregation in
      the human platelet rich plasma assay with IC50 values below 50 nM. Using a
      homology and a three-dimensional quantitative structure-activity relationship
      model, a binding hypothesis elucidating the impact of several structural features
      was developed.

PMID- 22984836
TI  - Optimization of the dispersion of unmodified bacterial cellulose nanowhiskers
      into polylactide via melt compounding to significantly enhance barrier and
      mechanical properties.
AB  - In the present study, property-enhanced polylactide (PLA) nanocomposites
      containing bacterial cellulose nanowhiskers (BCNW) were prepared by melt
      compounding. With the aim of improving the nanocrystals' dispersion in the final
      melt processed nanocomposites, these were preincorporated either into PLA
      nanostructured fibers by electrospinning or into an ethylene vinyl-alcohol
      copolymer (EVOH) by solution precipitation. An optimized dispersion of the
      nanofiller in the nanocomposites produced by applying these preincorporation
      methods, when compared to the direct melt mixing of the freeze-dried nanowhiskers
      with the polymeric matrix, was confirmed by morphological studies. Enhanced
      dispersion of BCNW was critical for enhancing the barrier and mechanical
      properties of the nanocomposites. Thus, for concentrations around the percolation
      threshold, that is, 2-3 wt % BCNW, nanocomposites produced by the electrospinning
      preincorporation method showed increased elastic modulus and tensile strength,
      preserving the ductility of the pure PLA. Moreover, in the optimized
      nanocomposites the water permeability of PLA was reduced by 43% and the oxygen
      barrier also decreased to a significant extent. This paper provides a successful
      route to solve the long-standing issue related to the dispersion of highly polar
      unmodified cellulose nanowhiskers into PLA via the industrially meaningful melt
      compounding processing.

PMID- 22984837
TI  - Near-interfacial halogen atom exchange in collisions of Cl2 with 2.7 M NaBr
      glycerol.
AB  - Gas-liquid scattering experiments are used to investigate reactions of Cl(2) with
      a 2.7 M NaBr-glycerol solution at 291 K. Only the single and double halogen
      exchange products, BrCl and Br(2), are observed to desorb from solution. When
      Cl(2) molecules strike the surface at thermal collision energies, 76% desorb as
      Cl(2) before reacting, 1% react to form BrCl, and 23% react to form Br(2).
      Residence time measurements, modeled by mass-transfer equations for absorption,
      diffusion, reaction, and evaporation, were used to determine the time and depth
      scales for Cl(2) escape and BrCl and Br(2) production. This modeling indicates
      that Cl(2) molecules desorb from the interfacial region in less than 1 MUs or are
      attacked within this time by Br(-) ions and irreversibly captured as Cl(2)Br(-).
      The products BrCl and Br(2) are created primarily within the top few monolayers
      of the solution and then evaporate on average 12 and 28 MUs after Cl(2) initially
      reacts with Br(-). Notably, Br(2) is not generated from BrCl via Cl(2)Br(-) ->
      BrCl + Cl(-) and BrCl + Br(-) -> Br(2)Cl(-) but from the parallel reaction
      Cl(2)Br(-) + Br(-) -> Br(2)Cl(-)+ Cl(-) that bypasses the BrCl intermediate.
      Br(2) is then likely released through two pathways, Br(2)Cl(-) -> Br(2) + Cl(-)
      and Br(2)Cl(-) + Br(-) -> Br(3)(-) + Cl(-), followed by Br(3)(-) <-> Br(2) + Br(
      ). The experiments demonstrate that single and double halogen exchange reactions
      can occur rapidly and close to the surface even when the products are created by
      multiple sequential reactions.

PMID- 22984838
TI  - Fitting distributions to microbial contamination data collected with an unequal
      probability sampling design.
AB  - AIMS: The fitting of statistical distributions to microbial sampling data is a
      common application in quantitative microbiology and risk assessment applications.
      An underlying assumption of most fitting techniques is that data are collected
      with simple random sampling, which is often times not the case. This study
      develops a weighted maximum likelihood estimation framework that is appropriate
      for microbiological samples that are collected with unequal probabilities of
      selection. METHODS AND RESULTS: A weighted maximum likelihood estimation
      framework is proposed for microbiological samples that are collected with unequal
      probabilities of selection. Two examples, based on the collection of food samples
      during processing, are provided to demonstrate the method and highlight the
      magnitude of biases in the maximum likelihood estimator when data are
      inappropriately treated as a simple random sample. CONCLUSIONS: Failure to
      properly weight samples to account for how data are collected can introduce
      substantial biases into inferences drawn from the data. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The proposed methodology will reduce or eliminate an important
      source of bias in inferences drawn from the analysis of microbial data. This will
      also make comparisons between studies and the combination of results from
      different studies more reliable, which is important for risk assessment
      applications.

PMID- 22984839
TI  - Epileptic high-frequency oscillations in intraoperative electrocorticography: the
      effect of propofol.
AB  - PURPOSE: Epileptic high-frequency oscillations (HFOs; 80-500 Hz) may be used to
      guide neurosurgeons during epilepsy surgery to identify epileptogenic tissue. We
      studied the effect of the anesthetic agent propofol on the occurrence of HFOs in
      intraoperative electrocorticography (ECoG). METHODS: We selected patients who
      were undergoing surgery for temporal lobe epilepsy with a standardized electrode
      grid placement. Intraoperative ECoG was recorded at 2,048 Hz following cessation
      of propofol. The number and distribution of interictal spikes, ripples (R [80-250
      Hz]), and fast ripples (FRs; 250-500 Hz) were analyzed. The amount of events on
      mesiotemporal channels and lateral neocortical channels were compared between
      patients with a suspected mesiotemporal and lateral epileptogenic area (Student's
      t-test), and HFOs were compared with the irritative zone, using correlation
      between amounts of events per channel, to provide evidence for the epileptic
      nature of the HFOs. Next, the amount of events within the first minute and the
      last minute were compared to each other and the change in events over the entire
      epochs was analyzed using correlation analyses of 10 epochs during the emergence
      periods (Spearman rank test). We studied whether the duration of HFOs changed
      over time. The change in events within presumed epileptogenic area was compared
      to the change outside this area (Student's t-test). Periods of burst suppression
      and continuous background activity were compared between and within patients (t
      test). KEY FINDINGS: Twelve patients were included: five with suspected
      mesiotemporal epileptogenic area and three with suspected lateral epileptogenic
      area (and four were "other"). Spikes, ripples, and FRs were related to the
      suspected epileptogenic areas, and HFO zones were related to the irritative
      zones. Ripples and FRs increased during emergence from propofol anesthesia (mean
      number of ripples from first minute-last minute: 61.5-73.0, R = 0.46, p < 0.01;
      FRs: 3.1-5.7, R = 0.30, p < 0.01) and spikes remained unchanged (80.1-79.9, R = 
      0.05, p = 0.59). There was a decrease in number of channels with spikes (R = 
      0.18, p = 0.05), but no change in ripples (R = -0.13, p = 0.16) or FRs (R = 0.11,
      p = 0.45). There was no change in the durations of HFOs. The amount of HFOs in
      the presumed epileptogenic areas did not change more than the amount outside the
      presumed epileptogenic area, whereas spikes paradoxically decreased more within
      the suspected epileptogenic area. Six patients showing burst-suppression had
      lower rates of ripples than six other patients with continuous background
      activity (p = 0.02). No significant difference was found between burst
      suppression and continuous background activity in four patients, but there was a
      trend toward showing more ripples during continuous background activity (p =
      0.16). SIGNIFICANCE: Propofol, known for its antiepileptic effects, reduces the
      number of epileptic HFOs, but has no effect on spikes. This enforces the
      hypothesis that, in epilepsy, HFOs mirror the disease activity and HFOs might be
      useful for monitoring antiepileptic drug treatment. It is feasible to record HFOs
      during surgery, but propofol infusion should be interrupted for some minutes to
      improve detection.

PMID- 22984840
TI  - Association of violence against women with religion and culture in Erbil Iraq: a
      cross-sectional study.
AB  - BACKGROUND: Violence against women by intimate partners is still a public health
      problem. The study aims at finding out the prevalence of violence among women
      residing in Erbil city (Muslim culture) and in Ankawa sub-district (Christian
      culture), finding out the role of religion and culture on the prevalence, and
      finding out some other factors (like occupation of husband and wife, age at
      marriage, woman agreement for marriage, illegitimate relations of husband) that
      might be associated with violence. METHODS: A cross-sectional study was carried
      out in Erbil during the second half of the year 2011. Two groups were considered;
      group one (G1) included women residing in Ankawa sub-district (representing
      Christian culture), and group two (G2) included women residing in Erbil city
      (representing Muslim culture). A convenience method of sampling was used to
      collect the sample (250 women of each group). Questionnaire was designed to
      collect information about history of exposure to physical, sexual, and
      psychological violence, in addition to the related factors. These forms were
      distributed (by women of the Assyrian Women Union) in sealed envelopes to women
      attending the Mass in three churches located in Ankawa. Women of Erbil group were
      recruited from the maternity teaching hospital of Erbil. The same questionnaire
      was distributed to them by the same team. Binary logistic regression was used to
      show the independent effect of each factor on the prevalence of violence.
      RESULTS: Overall prevalence of violence (physical and/or sexual) in G2 (20.8%)
      was higher than that of G1 (18.8%). The prevalence of psychological violence was
      40% in Erbil, which was significantly higher than the prevalence (24.8%) of
      Ankawa. The rates of physical and sexual violence were also higher in Erbil
      (18.4%, and 10.8% respectively) than rates of Ankawa (16.8% and 8% respectively).
      Factors found to be significantly associated with overall violence were: culture
      of Erbil, alcoholic husband, wife working as manual worker (compared with
      professionals), and having children. CONCLUSION: Violence against women is a
      serious public health issue. There was significant role of culture on the
      prevalence of violence.

PMID- 22984841
TI  - A prosthetic alternative for severely angled implants beneath a maxillary
      overdenture: a clinical report.
AB  - Implant-retained overdentures have been shown to be a predictable, accepted
      option and represent a viable and cost-effective treatment; however, patients
      with severe lack of bone volume and anatomical limitations are often a
      contraindication to the placement of osseointegrated implants without prior
      surgical procedures. In these situations, the placement of angled implants may
      offer a simple solution. This clinical report describes a case of dental
      rehabilitation using angled implants for a patient with a severely resorbed
      edentulous maxilla. The inclination has been solved by making a bar on the right
      side and individual pillars on the left side so as to obtain a functional and
      esthetic prosthetic result.

PMID- 22984842
TI  - Comparison of point-of-care analysis using Coaguchek XS and standard laboratory
      measured prothrombin time in dogs.
AB  - AIMS: The Coaguchek XS is a hand-held coagulation monitor, which is widely
      available for human testing, and could have applications for canine samples. The
      aim of this study was a preliminary evaluation of the suitability of this point
      of-care device to determine prothrombin time (PT) in dogs by measuring the
      clinical agreement between the results obtained using the device and standard
      laboratory testing. METHODS: The PT in 24 samples from 13 dogs with suspected
      coagulopathy and 40 samples from 40 healthy dogs was determined concurrently
      using the point-of-care device and standard laboratory analysis. The clinical
      agreement between methods was assessed using Bland-Altman analysis and error grid
      analysis. RESULTS: Four of the paired samples were not suitable for analysis. The
      point-of-care device showed a 1.29 fold positive systematic bias which, when
      corrected for, gave excellent clinical agreement. Differences in the results
      obtained would have influenced clinical decision making in only 3 of 60 (5.0%)
      samples where the point-of-care result suggested a more prolonged PT than
      laboratory testing. A measurement error occurred in two point-of-care samples
      which may have been due to the combination of severe anaemia and severely
      prolonged PT. CONCLUSIONS AND CLINICAL RELEVANCE: The point-of-care device can be
      used in dogs and would provide rapid analysis of PT to aid clinical decision
      making in dogs with suspected rodenticide toxicity. Development of a device
      specific reference range for dogs would improve its value.

PMID- 22984843
TI  - Analytical detection of influenza A(H3N2)v and other A variant viruses from the
      USA by rapid influenza diagnostic tests.
AB  - BACKGROUND: The performance of rapid influenza diagnostic tests (RIDTs) that
      detect influenza viral nucleoprotein (NP) antigen has been reported to be
      variable. Recent human infections with variant influenza A viruses that are
      circulating in pigs prompted the investigation of the analytical reactivity of
      RIDTs with these variant viruses. OBJECTIVES: To determine analytical reactivity
      of seven FDA-cleared RIDTs with influenza A variant viruses in comparison with
      the reactivity with recently circulating seasonal influenza A viruses. METHODS:
      Tenfold serial dilutions of cell culture-grown seasonal and variant influenza A
      viruses were prepared and tested in duplicate with seven RIDTs. RESULTS: All
      RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus,
      although detection limits varied among assays. All but one examined RIDT
      identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs
      detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced
      sensitivity of RIDTs to variant influenza viruses may be due to amino acid
      differences between the NP proteins of seasonal viruses and the NP proteins from
      viruses circulating in pigs. CONCLUSIONS: Clinicians should be aware of the
      limitations of RIDTs to detect influenza A variant viruses. Specimens from
      patients with influenza-like illness in whom H3N2v is suspected should be sent to
      public health laboratories for additional diagnostic testing.

PMID- 22984844
TI  - Exploration and characterization of genes involved in the synthesis of diterpene
      defence secretion in nasute termite soldiers.
AB  - Nasutitermes takasagoensis soldiers defend their colonies using characteristic
      diterpenes. Diterpenes are thought to be synthesized in the frontal gland cells
      surrounding the gland reservoir. To identify the genes involved in diterpene
      synthesis, a cDNA library was prepared from the frontal gland cells and
      exhaustively sequenced using a 454 pyrosequencer (GS Junior; Roche, Branford, CT,
      USA). A total of 50,290 clean sequences were assembled into 1111 contigs, which
      were grouped into 774 genes (isogroups). Based on sequence similarity with known
      proteins, we identified seven genes encoding the following four enzymes
      associated with diterpene synthesis: 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) synthase (HMGS), HMG-CoA reductase (HMGR), farnesyl diphosphate synthase,
      and geranylgeranyl diphosphate synthases. The expression levels of two enzymes,
      HMGS and HMGR, involved in the mevalonate pathway were examined, assuming that
      the site of the defensive terpenoid synthesis strongly activates the mevalonate
      pathway, which produces a precursor of terpenoids. Real-time quantitative reverse
      transcriptase PCR confirmed significantly higher expression of HMGS and HMGR in
      the heads of soldiers. We then divided the head into three parts and found that
      the expression levels of HMGS and HMGR were significantly higher in the part
      containing class 1 secretory cells of the frontal gland. Overall, the results
      suggested that the mevalonate pathway for diterpene synthesis occurs in class 1
      cells around the frontal gland reservoir.

PMID- 22984845
TI  - Factors delaying chemotherapy for breast cancer in four urban and rural oncology
      units.
AB  - BACKGROUND: Delays in commencing adjuvant chemotherapy for early breast cancer
      beyond 12 weeks are associated with increased mortality. The aim of this study
      was to identify factors delaying chemotherapy in an inner metropolitan, outer
      metropolitan, small rural and large rural cancer centre in New South Wales,
      Australia. METHODS: We retrospectively reviewed 400 consecutive patients that
      received adjuvant chemotherapy for stages I-III breast cancer. We evaluated
      factors affecting time from primary and definitive surgery until commencing
      chemotherapy. RESULTS: The primary factor associated with chemotherapy delays was
      the geographic location of the cancer centre. The median time from primary
      surgery to chemotherapy was longer for the large rural centre (median 58 days),
      compared with the outer metropolitan (45 days), small rural (39 days) and inner
      metropolitan centre (33 days). Treatment delays in the large rural centre were
      associated with higher rates of multiple operations (43% versus 31% elsewhere),
      mainly because of more staged axillary dissections (34% versus 19%), and longer
      time from definitive surgery to oncology assessment. CONCLUSION: Patients in the
      large rural centre, who are served by fly-in medical oncology services, are more
      likely to experience delays in receiving adjuvant chemotherapy for early breast
      cancer. Strategies to reduce delays include use of intraoperative frozen section
      analysis, multidisciplinary meetings, improving efficiency in pathology reporting
      and employment of a breast cancer care coordinator and an on-site medical
      oncologist.

PMID- 22984846
TI  - One-pot transition-metal-free synthesis of dibenzo[b,f]oxepins from 2
      halobenzaldehydes.
AB  - A one-pot transition-metal-free, base-mediated synthesis of dibenzo[b,f]oxepins
      was developed. The reaction of 2-halobenzaldehydes with (2
      hydroxyphenyl)acetonitriles proceeds via a sequential aldol condensation and
      intramolecular ether formation reaction in the presence of Cs(2)CO(3) and
      molecular sieves in toluene.

PMID- 22984848
TI  - Renal hypothermia with ice slush in laparoscopic partial nephrectomy: the outcome
      of renal function.
AB  - PURPOSE: To investigate changes in renal function after retroperitoneal
      laparoscopic partial nephrectomy (LPN) with renal hypothermia induced by ice
      slush cooling. PATIENTS AND METHODS: Seventy-one patients undergoing
      retroperitoneal LPN with renal hypothermia were included. Perioperative outcomes
      were reviewed retrospectively. The total renal function was evaluated by an
      estimated glomerular filtration rate (eGFR) preoperatively and 6 months
      postoperatively in 69 patients. Split renal function (SRF) was also evaluated by
      99mTc-mercaptoacetyltriglycine scintigraphy preoperatively and 6 months
      postoperatively in 61 patients. RESULTS: The median operative time was 246
      minutes (range, 155-424). The median cold ischemic time, including the initial 15
      minutes of hypothermia, was 57 minutes (range, 34-112). In the 21 patients whose
      renal temperature was monitored, median lowest renal temperature was 20.7 degrees
      C (range, 12.1-27.6). The median baseline eGFR and 6-month postoperative eGFR
      were 77.2 mL/min/1.73 m(2) (range, 36.1-121.3) and 68.3 mL/min/1.73 m(2) (range,
      33.2-103.4), and the median baseline SRF and 6-month postoperative SRF of the
      affected kidney were 49.3% (range, 40.3-57.6) and 40.7% (range, 13.8-54.5). Using
      multivariate analysis, the baseline eGFR (p<0.0001) and the ischemic time
      (p=0.0073) were associated with the 6-month postoperative eGFR, and the 6-month
      postoperative SRF was only associated with a baseline SRF (p=0.0185).
      CONCLUSIONS: Ice-slush cooling could provide renal hypothermia also under LPN.
      The decrease in renal function was small, whereas our ischemic time was longer
      than experts' warm ischemic series. These observations suggested the protective
      effect of our cooling methods against ischemic injury.

PMID- 22984847
TI  - Anogenital distance and the risk of prostate cancer.
AB  - Study Type - Prognosis (cohort) Level of Evidence 2b What's known on the subject?
      and What does the study add? In animals, anogenital distance has been shown to be
      related to the action of fetal androgens, and exposure to chemicals such as
      dioxins that exhibit antiandrogenic activity results in shorter distances in male
      rats. In studies conducted in children, anogenital distance has been associated
      with endocrine disruptors such as phthalates. Studies conducted in young adults
      found that a shorter anoscrotal distance was a predictor of low sperm
      concentration, and a longer anoscrotal distance was associated with fatherhood, a
      higher sperm density and a higher total motile sperm count. The present study is
      the first to report anogenital measurements in adults in relation to the risk of
      cancer, showing that a phenotype reflecting normal in utero sexual development in
      males is associated with a lower risk of prostate cancer. There are two published
      studies evaluating sperm quality and fatherhood suggesting a connecting mechanism
      related to the disruption of androgen-mediated pathways in utero that affects
      reproductive potential and the risk of prostate cancer. OBJECTIVES: *  To measure
      anogenital distance in patients with prostate cancer and control subjects without
      cancer. *  To evaluate the association of anogenital distance with prostate
      cancer in a case-control study in Spain. MATERIALS AND METHODS: *  Anogenital
      distances from anus to upper penis (AGDAP ) and from anus to scrotum (AGDAS )
      were measured in 60 patients with prostate cancer in two hospitals in Barcelona
      and in 52 urological controls. *  Each measurement was performed three times by
      the same trained examiner using a digital caliper RESULTS: *  Patients had an ~5
      mm shorter AGDAP than controls, whereas no difference was observed for AGDAS . * 
      A higher AGDAP was associated with a lower risk of prostate cancer, with an
      adjusted odds ratio per 5 mm increase in AGDAP of 0.83 (95% confidence interval,
      0.70-0.99, P= 0.03). CONCLUSIONS: *  The present study is the first to report
      anogenital measurements in adults in relation to the risk of cancer. *  The
      present study showed that a phenotype reflecting normal in utero sexual
      development in men is associated with a lower risk of prostate cancer. *  There
      are two published studies (Mendiola et al. Environ Health Perspect 2011; 119: 958
      63; Eisenberg et al. PLoS One 2011; 6: e18973) evaluating sperm quality and
      fatherhood suggesting a connecting mechanism related to the disruption of
      androgen-mediated pathways in utero that affects reproductive potential and the
      risk of prostate cancer.

PMID- 22984849
TI  - Laparoendoscopic single-site radical nephrectomy for large renal masses.
AB  - PURPOSE: To report our operative experience and short-term outcomes for the
      laparoendoscopic single-site (LESS) management of large renal tumors and tumors
      of advanced stage. PATIENTS AND METHODS: Ten consecutive patients underwent LESS
      radical nephrectomy (RN) for large (>= 7 cm) and/or locally advanced tumors
      (>T(2)). Intraoperative, postoperative, and short-term follow-up data were
      analyzed. RESULTS: Median surgical time was 146 minutes (range 73-164 min), and
      median estimated blood loss was 100 mL (range 25-400 mL). No procedure needed
      conversion to open RN or hand-assisted laparoscopic RN. The median hospital stay
      was 47 hours (range 42 hours-12 days). One (10%) patient had a minor complication
      (postoperative fever treated with antibiotics) and one (10%) patient had a major
      complication (small bowel obstruction necessitating reoperation). Of the 10
      tumors, 2 were pathologic stage T(1b), 4 were pathologic stage T(2), and 4 were
      stage T(3a). At a median follow-up of 12.3 months (range 1-16 mos), six (60%)
      patients were alive without evidence of recurrence, and 4 (40%) patients were
      alive with disease. Of those four patients, all four had known metastatic disease
      before surgery. CONCLUSION: LESS-RN for large or advanced stage renal masses is a
      technically challenging operation. In experienced hands, however, it is a safe
      and feasible therapeutic option for the management of these tumors.

PMID- 22984850
TI  - Reliability, validity and administrative burden of the community reintegration of
      injured service members computer adaptive test (CRIS-CAT)".
AB  - BACKGROUND: The Computer Adaptive Test version of the Community Reintegration of
      Injured Service Members measure (CRIS-CAT) consists of three scales measuring
      Extent of, Perceived Limitations in, and Satisfaction with community integration.
      The CRIS-CAT was developed using item response theory methods. The purposes of
      this study were to assess the reliability, concurrent, known group and predictive
      validity and respondent burden of the CRIS-CAT.The CRIS-CAT was developed using
      item response theory methods. The purposes of this study were to assess the
      reliability, concurrent, known group and predictive validity and respondent
      burden of the CRIS-CAT. METHODS: This was a three-part study that included a 1) a
      cross-sectional field study of 517 homeless, employed, and Operation Enduring
      Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans; who completed all items in
      the CRIS item set, 2) a cohort study with one year follow-up study of 135 OEF/OIF
      Veterans, and 3) a 50-person study of CRIS-CAT administration. Conditional
      reliability of simulated CAT scores was calculated from the field study data, and
      concurrent validity and known group validity were examined using Pearson product
      correlations and ANOVAs. Data from the cohort were used to examine the ability of
      the CRIS-CAT to predict key one year outcomes. Data from the CRIS-CAT
      administration study were used to calculate ICC (2,1) minimum detectable change
      (MDC), and average number of items used during CAT administration. RESULTS:
      Reliability scores for all scales were above 0.75, but decreased at both ends of
      the score continuum. CRIS-CAT scores were correlated with concurrent validity
      indicators and differed significantly between the three Veteran groups (P <
      .001). The odds of having any Emergency Room visits were reduced for Veterans
      with better CRIS-CAT scores (Extent, Perceived Satisfaction respectively: OR =
      0.94, 0.93, 0.95; P < .05). CRIS-CAT scores were predictive of SF-12 physical and
      mental health related quality of life scores at the 1 year follow-up. Scales had
      ICCs >0.9. MDCs were 5.9, 6.2, and 3.6, respectively for Extent, Perceived and
      Satisfaction subscales. Number of items (mn, SD) administered at Visit 1 were
      14.6 (3.8) 10.9 (2.7) and 10.4 (1.7) respectively for Extent, Perceived and
      Satisfaction subscales. CONCLUSION: The CRIS-CAT demonstrated sound measurement
      properties including reliability, construct, known group and predictive validity,
      and it was administered with minimal respondent burden. These findings support
      the use of this measure in assessing community reintegration.

PMID- 22984851
TI  - Temporal succession of putative glycolate-utilizing bacterioplankton tracks
      changes in dissolved organic matter in a high-elevation lake.
AB  - Shifts in the composition of dissolved organic matter (DOM) may be a principal
      factor effecting changes in bacterial community composition. Emerald Lake, a high
      elevation lake with DOM dominated by terrestrial sources in the spring with
      increasing phytoplankton-derived inputs throughout the ice-free season, provided
      a natural experiment with which to investigate the importance of resource
      mediated drivers. Glycolate-utilizing bacteria, a subset of the bacterial
      community able to use algal exudates, were characterized using DNA analysis of
      glycolate oxidase subunit D (glcD) genes from Emerald Lake samples collected
      approximately biweekly from ice-cover (June) through fall turnover (September).
      glcD genes were not detected in early-season samples when the lake was ice
      covered and phytoplankton-derived resources were scarce. Following this period,
      glcD gene composition exhibited significant changes through time, which were
      strongly correlated with the combination of fluorescence index, an indicator of
      the proportion of lake vs. terrestrially derived DOM, and dissolved inorganic
      nitrate + nitrite. These results suggest that seasonal shifts in DOM source and
      environmental variables that affect the composition of algal-derived dissolved
      resources drive changes in the relative abundance and composition of putative
      glycolate-utilizing bacteria. These findings strengthen the evidence for shifts
      in DOM structuring bacterial communities.

PMID- 22984853
TI  - Ecological momentary assessment in borderline personality disorder: a review of
      recent findings and methodological challenges.
AB  - The use of Ecological Momentary Assessment (EMA) has led to increased insight
      into borderline personality disorder (BPD) symptoms, especially regarding
      affective instability. EMA is characterized by a series of repeated assessments
      of current affective, behavioral, and contextual experiences or physiological
      processes while participants engage in normal daily activities. EMA has several
      advantages. It enables researchers to avoid biased recollection, to investigate
      within-person processes, and to enhance real-life generalizability. This review
      is dedicated to four main objectives: (1) to discuss the characteristics of EMA
      in studying BPD symptomatology; (2) to provide an extensive overview of EMA
      findings in BPD structured into findings regarding DSM-IV criteria and findings
      regarding emotional dysregulation as stated in the biosocial theory of Linehan;
      (3) to discuss challenges of EMA and to give recommendations for the proper use
      of it; and (4) to highlight prospects and promising applications that should be
      addressed. 

PMID- 22984854
TI  - Serotonin (5-HT) augmentation reduces provoked aggression associated with primary
      psychopathy traits.
AB  - Psychopathy has long been associated with aggressive behavior; however, the
      neurochemical underpinnings of this relationship are poorly understood. Serotonin
      (5-HT) neurotransmitter system abnormalities have been associated with provoked
      aggression in general. In addition, 5-HT dysregulation has been linked to
      empathy, a trait that is lacking in individuals who score high on primary
      psychopathy. The purpose of this study was to determine if 5-HT modulates the
      relationship between psychopathic traits and aggression. Participants (N = 47)
      completed a self-report measure of psychopathy and were then administered either
      40 mg paroxetine (acutely augmenting 5-HT) or placebo. Aggression was assessed
      during a competitive reaction-time game in which electric shocks were exchanged
      with an increasingly provocative fictitious opponent. Results indicated that
      primary psychopathy (but not secondary psychopathy) was related to aggressive
      responding to provocation. Moreover, 5-HT augmentation attenuated this effect,
      supporting the notion that aggressive responding associated with primary
      psychopathic traits may be due in part to 5-HT dysregulation. 

PMID- 22984856
TI  - Factor structure and construct validity of the Self-Report Psychopathy (SRP)
      scale and the Youth Psychopathic Traits Inventory (YPI) in young men.
AB  - A large sample (N = 425) of young adult males from the Pittsburg Youth Study
      (PYS; Loeber, Farrington, Stouthamer-Loeber, & Van Kammen, 1998) was used to test
      the item-level structure of the short-form version of the Self-Report Psychopathy
      Scale (SRP; Paulhus, Neumann, & Hare, in press) and the standard version of the
      Youth Psychopathic Traits Inventory (YPI; Andershed, Kerr, Stattin, & Levander,
      2002). Also, structural equation modeling analyses examined how the SRP and YPI
      factors were linked to external correlates involving criminal offenses and
      internalizing and externalizing psychopathology. The modeling results indicated
      acceptable fit for the latent structure of both instruments and the SRP and YPI
      factor correlations were strong, particularly for conceptually-related scales.
      Finally, both instruments showed similar patterns in predicting externalizing and
      internalizing psychopathology, as well as criminal offenses. Taken together, the
      results provide evidence of convergent and construct validity across the two
      instruments. New insights into the link between psychopathy and the external
      correlates in young adult males are discussed. 

PMID- 22984858
TI  - Personality disorders in men with sexual and violent criminal offense histories.
AB  - Little is known about personality disorders (PDs) in offenders with histories of
      both sexual and (nonsexual) violent offenses. This study aimed to identify
      possible differences of PD profiles across three different offender groups with
      both sexual and violent (S+V), only sexual (S), and only violent (V) offenses.
      Nonviolent (N) offenders were used as a comparison group. Typing of individuals
      according to their offensive histories was performed on the basis of 259
      psychiatric court reports that included the Structured Clinical Interview (SCID)
      II for PD diagnostics. Men from the S+V group committed significantly more acts
      of rape and sexual coercion than the mere sexual offenders. Furthermore, S+V
      offenders showed the highest rates of PDs overall (68.3%), with every second
      offender being diagnosed with an antisocial PD and every third offender with a
      borderline PD. In summary, the results suggest that S+V offenders form a group of
      individuals with remarkable differences regarding PD profiles, the relatively
      highest frequencies of conduct disorders, familial addictive problems, and PDs
      overall. 

PMID- 22984859
TI  - Social context of anger in borderline personality disorder and depressive
      disorders: findings from a naturalistic observation study.
AB  - Anger and affective instability are key features of borderline personality
      disorder (BPD). Given the dynamic nature of affect, it is ideally studied using
      ambulatory assessment (AA). Recently, several major studies have examined
      affective instability via momentary self-report, using electronic diaries, which
      participants can use throughout their daily routine. The present study sought to
      complement this research by using an unobtrusive naturalistic observation method,
      the Electronically Activated Recorder (EAR). The EAR, which captures
      interpersonal behavior by periodically recording 50-second snippets of ambient
      sounds, was worn by 25 participants with BPD who also met the specific affective
      instability (AI) criterion as well as 13 participants with a depressive disorder
      (who did not meet criteria for AI or BPD) for three days. Trained coders listened
      to the captured recordings and rated participants' affect during each 50-second
      clip (i.e., in naturally varying social contexts). Results suggested that there
      were differences between diagnostic groups regarding the social context of anger,
      such that anger at a previous time interval predicted spending time alone in the
      subsequent time interval for the depressed group, but not for the BPD group. As
      an ambulatory observational method, the EAR offers an alternative to self-report
      and can provide insight into the naturalistic expression of emotions in BPD. 

PMID- 22984861
TI  - The Invalidating Childhood Environment Scale (ICES): psychometric properties and
      relationship to borderline personality symptomatology.
AB  - The objective of this study was to examine the psychometric properties of the
      Invalidating Childhood Environment Scale (ICES; Mountford, Corstorphine,
      Tomlinson, & Waller, 2004), a measure designed to retrospectively assess exposure
      to parental invalidation. The ICES was administered to a sample of female college
      students along with measures of parental bonding and borderline personality
      disorder (BPD) symptomatology. In contrast with previous findings, the ICES
      demonstrated excellent internal consistency within a nonclinical sample. It also
      correlated in the predicted directions with measures of parental bonding and BPD
      symptomatology. Taken together, these findings suggest that the ICES is a
      promising retrospective measure of parental invalidation. They also provide some
      support for the hypothesized link between parental invalidation and BPD
      symptomatology and suggest that additional research with clinical samples is
      needed.

PMID- 22984860
TI  - Socioeconomic-status and mental health in a personality disorder sample: the
      importance of neighborhood factors.
AB  - This cross-sectional study examined the associations between neighborhood-level
      socioeconomic-status (NSES), and psychosocial functioning and personality
      pathology among 335 adults drawn from the Collaborative Longitudinal Personality
      Disorders Study. Participants belonged to four personality disorder (PD)
      diagnostic groups: Avoidant, Borderline, Schizotypal, and Obsessive Compulsive.
      Global functioning, social adjustment, and PD symptoms were assessed following a
      minimum two-year period of residential stability. Residence in higherrisk
      neighborhoods was associated with more PD symptoms and lower levels of
      functioning and social adjustment. These relationships were consistent after
      controlling for individual-level socioeconomic-status and ethnicity; however, the
      positive association between neighborhood-level socio-economic risk and PD
      symptoms was evident only at higher levels of individual-level socio-economic
      risk. Our findings identify NSES as a candidate for explaining some of the
      variability in symptoms and functioning among PD individuals. 

PMID- 22984862
TI  - Brief report: relationships between facets of impulsivity and borderline
      personality features.
AB  - Relationships between specific borderline personality disorder (BPD) features and
      facets of impulsivity (negative and positive urgency, premeditation,
      perseverance, and sensation seeking) were examined in a sample of 227
      undergraduate students, oversampled to include many with elevations on a measure
      of borderline features. Most facets of impulsivity were positively correlated
      with borderline features, except for sensation seeking, which showed a mixed
      pattern of relationships with specific BPD features. In regression models,
      negative urgency was the strongest predictor of all BPD features scales,
      including affective instability, identity problems, negative relationships, and
      self-harm. Premeditation, positive urgency, and sensation seeking demonstrated
      incremental validity over negative urgency in predicting some BPD features;
      however, significant beta weights were negative for sensation seeking, suggesting
      that it may be protective or adaptive for BPD, unlike other forms of impulsivity.
      This study provides evidence for variation in how types of impulsivity contribute
      to different BPD features and demonstrates the importance of examining BPD
      features on the subscale level. 

PMID- 22984863
TI  - Dimensions of personality and personality pathology: factor structure of the
      Shedler-Westen assessment procedure-II (SWAP-II).
AB  - Researchers have proposed replacing the current system for diagnosing personality
      disorders with a dimensional trait model. Proposed trait models have been derived
      primarily from data provided by untrained lay informants (often via self-report
      questionnaires) using item sets derived from lay conceptions of personality. An
      alternative is to derive personality trait dimensions from data provided by
      clinically expert informants using an instrument that includes personality
      features salient to clinicians who treat personality dysfunction. The authors
      report the factor structure of the latest edition of the Shedler-Westen
      Assessment Procedure (SWAP-II) using a normative clinical sample of 1,201 North
      American patients assessed by experienced psychologists and psychiatrists. Factor
      analysis identified 14 clinically and empirically coherent factors. The findings
      highlight dimensions of personality and personality pathology that have not
      emerged in personality item sets designed for lay personality description. 

PMID- 22984866
TI  - A proposed explanation for increased risk of active tuberculosis in children with
      allergic disease.

PMID- 22984865
TI  - Spirocyclic sulfamides as beta-secretase 1 (BACE-1) inhibitors for the treatment
      of Alzheimer's disease: utilization of structure based drug design, WaterMap, and
      CNS penetration studies to identify centrally efficacious inhibitors.
AB  - beta-Secretase 1 (BACE-1) is an attractive therapeutic target for the treatment
      and prevention of Alzheimer's disease (AD). Herein, we describe the discovery of
      a novel class of BACE-1 inhibitors represented by sulfamide 14g, using a
      medicinal chemistry strategy to optimize central nervous system (CNS) penetration
      by minimizing hydrogen bond donors (HBDs) and reducing P-glycoprotein (P-gp)
      mediated efflux. We have also taken advantage of the combination of structure
      based drug design (SBDD) to guide the optimization of the sulfamide analogues and
      the in silico tool WaterMap to explain the observed SAR. Compound 14g is a potent
      inhibitor of BACE-1 with excellent permeability and a moderate P-gp liability.
      Administration of 14g to mice produced a significant, dose-dependent reduction in
      central Abeta(X-40) levels at a free drug exposure equivalent to the whole cell
      IC(50) (100 nM). Furthermore, studies of the P-gp knockout mouse provided
      evidence that efflux transporters affected the amount of Abeta lowering versus
      that observed in wild-type (WT) mouse at an equivalent dose.

PMID- 22984867
TI  - Altered theta coupling between medial entorhinal cortex and dentate gyrus in
      temporal lobe epilepsy.
AB  - PURPOSE:   Temporal lobe epilepsy is often accompanied by neuron loss and
      rewiring in the hippocampus. We hypothesized that the interaction of subnetworks
      of the entorhinal-hippocampal loop between epileptic events should show
      significant signatures of these pathologic changes. METHODS:   We combined
      simultaneous recording of local field potentials in entorhinal cortex (EC) and
      dentate gyrus (DG) in freely behaving kainate-injected mice with histologic
      analyses and computational modeling. KEY FINDINGS:   In healthy mice, theta band
      activity was synchronized between EC and DG. In contrast, in epileptic mice,
      theta activity in the EC was delayed with respect to the DG. A computational
      neural mass model suggests that hippocampal cell loss imbalances the coupling of
      subnetworks, introducing the shift. SIGNIFICANCE:   We show that pathologic
      dynamics in epilepsy encompass ongoing activity in the entorhinal-hippocampal
      loop beyond acute epileptiform activity. This predominantly affects theta band
      activity, which links this shift in entorhinal-hippocampal interaction to
      behavioral aspects in epilepsy.

PMID- 22984869
TI  - Sandwich-lithiation and longitudinal crack in amorphous silicon coated on carbon
      nanofibers.
AB  - Silicon-carbon nanofibers coaxial sponge, with strong mechanical integrity and
      improved electronic conductivity, is a promising anode structure to apply into
      commercial high-capacity lithium ion batteries. We characterized the
      electrochemical and mechanical behaviors of amorphous silicon-coated carbon
      nanofibers (a-Si/CNFs) with in situ transmission electron microscopy (TEM). It
      was found that lithiation of the a-Si coating layer occurred from the surface and
      the a-Si/CNF interface concurrently, and propagated toward the center of the a-Si
      layer. Such a process leads to a sandwiched Li(x)Si/Si/Li(x)Si structure,
      indicating fast Li transport through the a-Si/CNF interface. Nanocracks and
      sponge-like structures developed in the a-Si layer during the lithiation
      delithiation cycles. Lithiation of the a-Si layer sealed in the hollow CNF was
      also observed, but at a much lower speed than the counterpart of the a-Si layer
      coated on the CNF surface. An analytical solution of the stress field was
      formulated based on the continuum theory of finite deformation, explaining the
      experimental observation of longitudinal crack formation and general mechanical
      degradation mechanism in a-Si/CNF electrode.

PMID- 22984870
TI  - Fragmentation of the fluorite type in Fe8Al(17.4)Si(7.6): structural complexity
      in intermetallics dictated by the 18 electron rule.
AB  - This Article presents the synthesis, structure determination, and bonding
      analysis of Fe(8)Al(17.4)Si(7.6). Fe(8)Al(17.4)Si(7.6) crystallizes in a new
      monoclinic structure type based on columns of the fluorite (CaF(2)) structure
      type. As such, the compound can be seen as part of a structural series in which
      the fluorite structure-adopted by several transition metal disilicides (TMSi(2))
      is fragmented by the incorporation of Al. Electronic structure analysis using
      density functional theory (DFT) and DFT-calibrated Huckel calculations indicates
      that the fluorite-type TMSi(2) phases (TM = Co, Ni) exhibit density of states
      (DOS) pseudogaps near their Fermi energies. An analogous pseudogap occurs for
      Fe(8)Al(17.4)Si(7.6), revealing that its complex structure serves to preserve
      this stabilizing feature of the electronic structure. Pursuing the origins of
      these pseudogaps leads to a simple picture: the DOS minimum in the TMSi(2)
      structures arises via a bonding scheme analogous to those of 18 electron
      transition metal complexes. Replacement of Si with Al leads to the necessity of
      increasing the (Si/Al):TM ratio to maintain this valence electron concentration.
      The excess Si/Al atoms are accommodated through the fragmentation of the fluorite
      type. The resulting picture highlights how the elucidating power of bonding
      concepts from transition metal complexes can extend into the intermetallic realm.

PMID- 22984868
TI  - "Maybe his blood is still strong": a qualitative study among HIV-sero-discordant
      couples on ART in rural Uganda.
AB  - BACKGROUND: HIV-negative members of sero-discordant couples are at high risk for
      HIV acquisition but few behavioral prevention interventions have been implemented
      in sub-Saharan Africa and discordance is not well understood by couples
      themselves. METHODS: In this nested sub-study, we interviewed 40 HIV sero
      discordant couples before and after a 6-month behavioral intervention that was
      comprised of four group discussions on specific HIV prevention and care topics.
      The content of the sessions included: 1) understanding HIV serodiscordance and
      reducing risk, 2) couple communication, 3) reproductive health and HIV
      serodiscordance, 4) coping with HIV serodiscordance and ongoing support. Couple
      members were interviewed individually. Data were analyzed thematically using
      'Framework Analysis' which incorporated dyadic factors to address couple issues.
      RESULTS: Analysis revealed pre-identified concepts and emergent themes that were
      relevant to the final conceptual model. Four major categories of factors
      affecting couple relations, beliefs and current risk behaviors emerged:
      intervention factors, structural/contextual factors, physical health factors, and
      past risk behavior. The topics within the intervention most relevant were
      communication and reproductive health. The contextual factors highlighted by
      couples were gender norms around sexual decision-making and multiple
      partnerships. Individual beliefs regarding HIV serodiscordance persisted over all
      time points for some couples. Interestingly, some couple members had divergent
      views about their HIV status; some believing the HIV-negative member was negative
      while others described multiple beliefs around the negative member's blood surely
      being positive for HIV. Couple communication emerged as an important theme
      mediating beliefs and behavior. CONCLUSIONS: In addition to biomedical and
      behavioral interventions, HIV-serodiscordant couple interventions must embrace
      the contextual complexity and cultural understanding of HIV infection and
      discordance as well as the dynamic nature of couple communication to influence
      risk behavior.

PMID- 22984871
TI  - Rapid culture-independent microbial analysis aboard the international space
      station (ISS) stage two: quantifying three microbial biomarkers.
AB  - Abstract   A portable, rapid, microbial detection unit, the Lab-On-a-Chip
      Application Development Portable Test System (LOCAD-PTS), was launched to the
      International Space Station (ISS) as a technology demonstration unit in December
      2006. Results from the first series of experiments designed to detect Gram
      negative bacteria on ISS surfaces by quantifying a single microbial biomarker
      lipopolysaccharide (LPS) were reported in a previous article. Herein, we report
      additional technology demonstration experiments expanding the on-orbit
      capabilities of the LOCAD-PTS to detecting three different microbial biomarkers
      on ISS surfaces. Six different astronauts on more than 20 occasions participated
      in these experiments, which were designed to test the new beta-glucan (fungal
      cell wall molecule) and lipoteichoic acid (LTA; Gram-positive bacterial cell wall
      component) cartridges individually and in tandem with the existing Limulus
      Amebocyte Lysate (LAL; Gram-negative bacterial LPS detection) cartridges.
      Additionally, we conducted the sampling side by side with the standard culture
      based detection method currently used on the ISS. Therefore, we present data on
      the distribution of three microbial biomarkers collected from various surfaces in
      every module present on the ISS at the time of sampling. In accordance with our
      previous experiments, we determined that spacecraft surfaces known to be
      frequently in contact with crew members demonstrated higher values of all three
      microbial molecules. Key Words: Planetary protection-Spaceflight-Microbiology
      Biosensor. Astrobiology 12, 830-840.

PMID- 22984872
TI  - The O/OREOS mission: first science data from the space environment viability of
      organics (SEVO) payload.
AB  - We report the first science results from the Space Environment Viability of
      Organics (SEVO) payload aboard the Organism/Organic Exposure to Orbital Stresses
      (O/OREOS) free-flying nanosatellite, which completed its nominal spaceflight
      mission in May 2011 but continues to acquire data biweekly. The SEVO payload
      integrates a compact UV-visible-NIR spectrometer, utilizing the Sun as its light
      source, with a 24-cell sample carousel that houses four classes of vacuum
      deposited organic thin films: polycyclic aromatic hydrocarbon (PAH), amino acid,
      metalloporphyrin, and quinone. The organic films are enclosed in hermetically
      sealed sample cells that contain one of four astrobiologically relevant
      microenvironments. Results are reported in this paper for the first 309 days of
      the mission, during which the samples were exposed for ~2210 h to direct solar
      illumination (~1080 kJ/cm(2) of solar energy over the 124-2600 nm range).
      Transmission spectra (200-1000 nm) were recorded for each film, at first daily
      and subsequently every 15 days, along with a solar spectrum and the dark response
      of the detector array. Results presented here include eight preflight and 16 in
      flight spectra of eight SEVO sample cells. Spectra from the PAH thin film in a
      water-vapor-containing microenvironment indicate measurable change due to solar
      irradiation in orbit, while three other nominally water-free microenvironments
      show no appreciable change. The quinone anthrarufin showed high photostability
      and no significant spectroscopically measurable change in any of the four
      microenvironments during the same period. The SEVO experiment provides the first
      in situ real-time analysis of the photostability of organic compounds and
      biomarkers in orbit.

PMID- 22984874
TI  - The Astrobiology in Secondary Classrooms (ASC) curriculum: focusing upon diverse
      students and teachers.
AB  - The Minority Institution Astrobiology Collaborative (MIAC) began working with the
      NASA Goddard Center for Astrobiology in 2003 to develop curriculum materials for
      high school chemistry and Earth science classes based on astrobiology concepts.
      The Astrobiology in Secondary Classrooms (ASC) modules emphasize
      interdisciplinary connections in astronomy, biology, chemistry, geoscience,
      physics, mathematics, and ethics through hands-on activities that address
      national educational standards. Field-testing of the Astrobiology in Secondary
      Classrooms materials occurred over three years in eight U.S. locations, each with
      populations that are underrepresented in the career fields of science,
      technology, engineering, and mathematics. Analysis of the educational research
      upon the high school students participating in the ASC project showed
      statistically significant increases in students' perceived knowledge and science
      reasoning. The curriculum is in its final stages, preparing for review to become
      a NASA educational product.

PMID- 22984873
TI  - Refining the genetic alphabet: a late-period selection pressure?
AB  - The transition from genomic ribonucleic acid (RNA) to deoxyribonucleic acid (DNA)
      in primitive cells may have created a selection pressure that refined the genetic
      alphabet, resulting from the global weakening of the N-glycosyl bonds. Hydrolytic
      rupture of these bonds, termed deglycosylation, leaves an abasic site that is the
      single greatest threat to the stability and integrity of genomic DNA. The rates
      of deglycosylation are highly dependent on the identity of the nucleobases.
      Modifications made to the bases, such as deamination, oxidation, and alkylation,
      can further increase deglycosylation reaction rates, suggesting that the native
      bases provide optimum N-glycosyl bond stability. To protect their genomes, cells
      have evolved highly specific enzymes called glycosylases, associated with DNA
      repair, that detect and remove these damaged bases. In RNA, however, the
      occurrence of many of these modified bases is deliberate. The dichotomous
      behavior that cells exhibit toward base modifications may have originated in the
      RNA world. Modified bases would have been advantageous for the functional and
      structural repertoire of catalytic RNAs. Yet in an early DNA world, the utility
      of these heterocycles was greatly diminished, and their presence posed a distinct
      liability to the stability of cells' genomes. A natural selection for bases
      exhibiting the greatest resistance to deglycosylation would have ensured the
      viability of early DNA life, along with the recruitment of DNA repair.

PMID- 22984875
TI  - Hydrogen bonds and conformations in ethylene glycol under pressure.
AB  - Ethylene glycol (EG) is a model system for studying complex hydrogen bonding
      networks in biological compounds such as polysaccharides and sugars. Using in
      situ high-pressure Raman and infrared absorption spectroscopy, we have
      investigated the pressure induced variation in the conformations and hydrogen
      bonding interactions in this compound up to 10 GPa. The high-pressure behavior of
      Raman modes suggests that EG exists as a liquid with a mixture of trans and
      gauche conformations up to 3.1 GPa. At ~4 GPa, a liquid-solid transition is
      evidenced by the appearance of external Raman modes as well as visual
      observation. Raman and infrared spectra of EG at high pressures indicate that new
      hydrogen bonding networks are formed prior to liquid-solid transition and the
      high pressure phase is stabilized to gauche conformation at pressures above 5
      GPa.

PMID- 22984876
TI  - Helping veterans with mental illness overcome civil legal issues: collaboration
      between a veterans affairs psychosocial rehabilitation center and a nonprofit
      legal center.
AB  - This article describes the collaboration between a Department of Veterans Affairs
      (VA) community-based psychosocial rehabilitation center and a nonprofit legal
      center that primarily addresses the civil legal issues of veterans who have
      mental illness and/or are homeless. The legal center is located on-site at the VA
      psychosocial rehabilitation center and serves veterans who receive VA mental
      health treatment and other social services. Once veterans establish contact with
      the legal center and authorize the release of their health information, legal
      center staff members work closely with VA clinicians to help veterans address
      legal issues that may be obstacles to recovery. Development of this collaboration
      is described, along with the legal center's funding, clientele, and operations.
      The most common types of civil legal matters the legal center handles are also
      briefly described. Experiences of the legal center suggest that professional aid
      for civil legal problems provided within VA facilities may be beneficial for
      veterans and warrants empirical study.

PMID- 22984877
TI  - Perceived barriers to care and provider gender preferences among veteran men who
      have experienced military sexual trauma: a qualitative analysis.
AB  - Research suggests that there may be unique barriers to accessing care among men
      who have experienced sexual trauma. The primary goal of the current research was
      to elucidate potential barriers to accessing military sexual trauma (MST)-related
      care for male veterans. A secondary goal was to explore whether veterans have
      preferences regarding the gender of clinicians providing MST-related care.
      Qualitative analyses were used to examine data collected from semistructured
      interviews conducted with 20 male veterans enrolled in Veterans Health
      Administration care who reported MST but who had not received any MST-related
      mental health care. Veterans identified a number of potential barriers, with the
      majority of reported barriers relating to issues of stigma and gender. Regarding
      provider gender preferences, veterans were mixed, with 50% preferring a female
      provider, 25% a male provider, and 25% reporting no gender preference. These
      preliminary data suggest that stigma, gender, and knowledge-related barriers may
      exist for men regarding seeking MST-related care. Interventions to address
      potential barriers, such as outreach interventions and providing gender-specific
      psychoeducation, may increase access to care for male veterans who report MST.

PMID- 22984878
TI  - Technology complementing military psychology programs and services in the Pacific
      Regional Medical Command.
AB  - The Tripler Army Medical Center is the only federal tertiary care hospital
      serving the Pacific Regional Medical Command. Due to Tripler's large area of
      responsibility, many behavioral health professionals are starting to employ more
      technology during their sessions. As explained in this article, virtual reality
      and telepsychology efforts are proving to benefit military service members and
      their families in the Pacific Rim.

PMID- 22984879
TI  - A demedicalized view of maternal distress: conceptualization and instrument
      development.
AB  - The goal of this article was to describe instrument development of a
      demedicalized, multidomain view of maternal distress, with psychological,
      relational, and situational manifestations. We developed a pilot instrument
      derived from our previous grounded theory conceptualization of maternal distress
      and administered it to a purposive sample of 100 low-income single mothers.
      Analyses testing the relationship between maternal distress and depressive
      symptoms, guilt, child rearing stress, and community needs variables suggested
      that the maternal distress inventory had convergent, discriminant, and concurrent
      validity. Not only was maternal distress distinct from depressive symptomology
      and generalized child rearing stress, it appeared to be more meaningfully
      associated with "real world" outcomes of interest to psychological service
      providers than purely psychological measures of the distress.

PMID- 22984880
TI  - Provider proximity as a predictor of referral rate and success.
AB  - The predictive utility of proximity of primary care providers (PCPs) to mental
      health providers (MHPs) in referral rate and referral success was examined.
      Referrals from all PCPs in three New Jersey primary care clinics with primary
      care mental health integration (PC-MHI) to MHPs for fiscal year 2009 (October 1,
      2008 through September 30, 2009) were included. Regression analyses supported the
      hypotheses that proximity significantly predicts both rate of referral per visit
      and rate of referral per unique patient. The hypothesis that proximity predicts
      referral success was not supported. Further research might seek to determine if
      additional variables moderate the relationship between provider proximity and
      referral rate. Implications of the findings for colocated programs were
      discussed.

PMID- 22984881
TI  - Suppression of inflammation by tumor-derived exosomes: a kind of natural liposome
      packaged with multifunctional proteins.
AB  - Exosomes are small-membrane vesicles secreted by hematopoietic and malignant
      epithelial cells as well as trophoblasts. The composition of cancerous exosomes
      has been proven to play pivotal roles in the maintenance of the microenvironment
      that is beneficial for the progression of cancer, such as Fas-ligand-triggered
      lymphocyte apoptosis. We supposed that the immunosuppressive effect of cancerous
      exosomes might be helpful in the treatment of diseases characterized by
      overactivation of the immune system and subsequent tissue injury. The aim of this
      study was to evaluate the protective effect of tumor-derived exosomes in the mice
      model of lipopolysaccharide (LPS)-induced inflammation. Tetrazolium (MTT) and DNA
      electrophoresis were used to measure the cytotoxicity of exosomes on lymphocytes.
      Pathologic observation of tissue sections, serologic analysis of aspartate
      aminotransferase/alanine aminotransferase (AST/ALT), and urinary analysis of
      protein were used to assess the protection effect of exosomes in LPS-induced
      multiorgan damage. In vitro outcomes of MTT and DNA electrophoresis showed the
      cytotoxicity of exosomes on lymphocytes. Together with the alleviation of organ
      damages evaluated by urine protein, serum AST/ALT, and pathologic analysis, we
      confirmed the possibility that pretreatment of mice with exosomes, produced by
      H22 hepatic tumor cells, resulted in protection against LPS-induced tissue
      damage, which is caused by overactivation of the immune system and inflammation
      response. This therapeutic strategy will raise an interesting way to search new
      therapeutics in pairs of diseases with complementarities in etiology and
      pathology, namely, a strategy of taking advantage of the mutual complementarities
      between diseases.

PMID- 22984882
TI  - Helically foldable diphenylureas as anion receptors: modulation of the binding
      affinity by the chain length.
AB  - Using a series of diphenylureas capable of folding to helical conformations, the
      binding trends have been compared between two anions of different sizes, chloride
      and sulfate. The binding constant for the sulfate ion steadily increases from
      monomer to pentamer as the chain length increases, but for the chloride ion it
      increases up until the trimer and then reaches a plateau.

PMID- 22984883
TI  - DNA barcoding Neotropical fishes: recent advances from the Pampa Plain,
      Argentina.
AB  - The fish fauna of the Pampa Plain, the southernmost distribution range of many
      Neotropical species, was barcoded in this study. COI sequences were analysed by
      means of distance (K2P/NJ) and character-based (ML) models, as well as the
      Barcode Index Number (BIN). K2P/NJ analysis was able to discriminate among all
      previously identified species while also revealing the likely occurrence of two
      cryptic species that were further supported by BIN and ML analyses. On the other
      hand, both BIN and ML were not able to discriminate between two species of
      Rineloricaria. Despite the small genetic divergence between A. cf. pampa and A.
      eigenmanniorum, a tight array of haplotypes was observed for each species in both
      the distance and character-based methods. Deep intraspecific divergences were
      detected in Cnesterodon decemmaculatus (5%) and Salminus brasiliensis (6%). For
      Salminus brasiliensis, these findings were further supported by character-based
      (ML) evidence and meristic and morphological data. Our results also showed that
      Pampa Plain representatives of Salminus brasiliensis, Rhamdia quelen, Hoplias
      malabaricus, Synbranchus marmoratus, Australoheros facetus, Oligosarcus jenynsii
      and Corydoras paleatus differed by more than 3% from their conspecifics from
      other parts of South America. Overall, this study was able to highlight the
      likely occurrence of a cryptic species in Salminus brasiliensis and also
      illustrate the strong geographical structure in the COI sequence composition of
      seven fish species from South America.

PMID- 22984884
TI  - Amyloid inspired self-assembled peptide nanofibers.
AB  - Amyloid peptides are important components in many degenerative diseases as well
      as in maintaining cellular metabolism. Their unique stable structure provides new
      insights in developing new materials. Designing bioinspired self-assembling
      peptides is essential to generate new forms of hierarchical nanostructures. Here
      we present oppositely charged amyloid inspired peptides (AIPs), which rapidly
      self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent
      interactions. Mechanical properties of the gels formed by self-assembled AIP
      nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong
      mechanical characteristics superior to gels formed by self-assembly of previously
      reported synthetic short peptides. Rheological studies of gels composed of
      oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical
      stability compared to individual peptide networks (AIP-1 and AIP-2) formed by
      neutralization of net charges through pH change. Adhesion and elasticity
      properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers
      were analyzed by high resolution force-distance mapping using atomic force
      microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2,
      AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and
      mechanical stability of AIP mixed nanofibers was higher compared to individual
      AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively.
      Experimental results were supported with molecular dynamics simulations by
      considering potential noncovalent interactions between the amino acid residues
      and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed
      nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties
      of the nanofibrous system were observed. Encapsulation of a zwitterionic dye
      (rhodamine B) within AIP nanofiber network was accomplished at physiological
      conditions to demonstrate that this network can be utilized for inclusion of
      soluble factors as a scaffold for cell culture studies.

PMID- 22984885
TI  - Environmentally induced dispersal-related life-history syndrome in the tropical
      butterfly, Bicyclus anynana.
AB  - Dispersal is a key process for understanding the persistence of populations as
      well as the capacity of organisms to respond to environmental change. Therefore,
      understanding factors that may facilitate or constrain the evolution of dispersal
      is of crucial interest. Assessments of phenotypic variation in various
      behavioural, physiological and morphological traits related to insect dispersal
      and flight performance are common, yet very little is known about the genetic
      associations among these traits. We have used experiments on the butterfly
      Bicyclus anynana to estimate genetic variation and covariation in seven
      behavioural, physiological and morphological traits related to flight potential
      and hence dispersal. Our goal was to characterize the heritabilities and genetic
      correlations among these traits and thus to understand more about the evolution
      of dispersal-related life-history syndromes in butterflies. Using a version of
      the animal model, we showed that all of the traits varied between the sexes, and
      most were either positively or negatively (phenotypically and/or genetically)
      correlated with body size. Heritable variation was present in most traits, with
      the highest heritabilities estimated for body mass and thorax ratio. The variance
      in flight activity among multiple measurements for the same individual was high
      even after controlling for the prevailing environmental conditions, indicating
      the importance of behavioural switching and/or inherent randomness associated
      with this type of movement. A number of dispersal-related traits showed
      phenotypic correlations among one another, but only a few of these were
      associated with significant genetic correlations indicating that covariances
      between these traits in Bicyclus anynana are mainly environmentally induced.

PMID- 22984886
TI  - Avipoxvirus infections in brown kiwi (Apteryx mantelli).
AB  - CASE HISTORY: Nodular lesions were found on the skin of two immature brown kiwi
      (Apteryx mantelli) less than 6 months of age living freely on Ponui Island off
      the North Island of New Zealand. The lesions were observed during routine
      external examination undertaken as a part of the management of other research
      projects, one in 2006 and the other in 2011. Apart from the skin lesions, both
      birds showed no signs of illness and the lesions resolved spontaneously over a 2
      month period. PATHOLOGICAL FINDINGS: The first case showed several 3-mm diameter
      firm, brown nodules located on the skin below the hock of both legs. The second
      case had a single multinodular mass that measured 7*20 mm, on the base of the
      bill. A portion of the mass and scab samples were collected for diagnosis.
      Histological examination of the nodules revealed severe ballooning degeneration
      of keratinocytes and epithelial hyperplasia. Round eosinophilic structures
      resembling avipoxvirus (APV) intracytoplasmic inclusion bodies (Bollinger bodies)
      were observed in the layers of keratinocytes. In deeper layers of the epidermis,
      there was evidence of secondary bacterial growth and inflammation. DIAGNOSIS: DNA
      was extracted from tissue samples and subjected to PCR analysis. Avipoxvirus 4b
      core protein gene was detected in both samples by PCR. Bootstrap analysis of APV
      4b core protein gene revealed that APV isolates from two kiwi comprised two
      different subclades. One isolate displayed 100% sequence homology to subclade B1,
      and the other presented 100% sequence homology to subclade A3. CLINICAL
      RELEVANCE: This study confirmed that kiwi are susceptible to APV infection and
      that at least two different strains of APV are present in the population
      examined. Since there is no information on the origin, virulence, or prevalence
      of APV in kiwi, a seroprevalence study would be useful to elucidate the degree of
      exposure and immune response to the disease. This would allow a more informed
      approach to risk management of the disease in wild and captive populations.

PMID- 22984888
TI  - Induction of apoptosis through tubulin inhibition in human cancer cells by new
      chromene-based chalcones.
AB  - CONTEXT: As microtubules are highly involved in cellular growth, it appears to be
      a preferential target for cancer treatment. Therefore, many efforts have been
      performed to discover drugs that affect on microtubule function. Several
      microtubule inhibitors are in various stages of laboratory evaluations and
      clinical trials. OBJECTIVE: A series of chromene-based chalcones with chlorine,
      methoxy, fluorine, tetrahydropyranyloxy and cyanide substituents were prepared
      and evaluated for cytotoxic effects against K562 and SK-N-MC cell lines, and the
      inhibitory effect on tubulin polymerization was studied as well. MATERIALS AND
      METHODS: MTT, tubulin polymerization assays and binding measurements were
      evaluated by using related spectroscopy. Immunocytochemical study, morphological
      observations and apoptosis assay were examined using a fluorescence microscope
      and a flow cytometer. RESULTS: (E)-3-(6-Chloro-2H-chromen-3-yl)-1-(3,4,5
      trimethoxyphenyl) prop-2-en-1-one (compound 14) proved to be the most active in
      this series as an inhibitor of tubulin assembly [IC50, 19.6 uM] and cytotoxic
      agent on K562 cells [IC50, 38.7 uM]. Furthermore, these compounds exhibited a
      strong inhibitory effect on tubulin polymerization and reduced the in vitro
      assembly and bundling of proto-filaments. Also, compound 14 bound to the tubulin
      with a dissociation constant of 9.4 +/- 0.7 uM and induced conformational changes
      in this protein. DISCUSSION AND CONCLUSION: This study suggests that the compound
      14 could be a good antitumor agent because of its biological functions. Compound
      14 appears to bind directly to tubulin and thereby perturbs microtubule stability
      and the function of the spindle apparatus, which causes cancer cells to arrest
      and undergo apoptosis.

PMID- 22984887
TI  - Modelling zoonotic diseases in humans: comparison of methods for hantavirus in
      Sweden.
AB  - Because their distribution usually depends on the presence of more than one
      species, modelling zoonotic diseases in humans differs from modelling individual
      species distribution even though the data are similar in nature. Three approaches
      can be used to model spatial distributions recorded by points: based on
      presence/absence, presence/available or presence data. Here, we compared one or
      two of several existing methods for each of these approaches. Human cases of
      hantavirus infection reported by place of infection between 1991 and 1998 in
      Sweden were used as a case study. Puumala virus (PUUV), the most common
      hantavirus in Europe, circulates among bank voles (Myodes glareolus). In northern
      Sweden, it causes nephropathia epidemica (NE) in humans, a mild form of
      hemorrhagic fever with renal syndrome.Logistic binomial regression and boosted
      regression trees were used to model presence and absence data. Presence and
      available sites (where the disease may occur) were modelled using cross-validated
      logistic regression. Finally, the ecological niche model MaxEnt, based on
      presence-only data, was used.In our study, logistic regression had the best
      predictive power, followed by boosted regression trees, MaxEnt and cross
      validated logistic regression. It is also the most statistically reliable but
      requires absence data. The cross-validated method partly avoids the issue of
      absence data but requires fastidious calculations. MaxEnt accounts for non-linear
      responses but the estimators can be complex. The advantages and disadvantages of
      each method are reviewed.

PMID- 22984889
TI  - Reliable and repeatable centric relation adjustment of the maxillary occlusal
      device.
AB  - This technique article describes a quantifiable, repeatable, and reliable method
      for occlusal device adjustment in centric relation using a leaf gauge. In
      addition, specific suggestions for occlusal device design are provided to enhance
      patient comfort with the prosthesis in place.

PMID- 22984890
TI  - Avoiding cracks in nanoparticle films.
AB  - A new method utilizing subsequent depositions of thin crack-free nanoparticle
      layers is demonstrated to avoid the formation of cracks within silica
      nanoparticle films. Using this method, films can be assembled with thicknesses
      exceeding the critical cracking values. Explanation of this observed phenomenon
      is hypothesized to mainly arise from chemical bond formation between neighboring
      silica nanoparticles. Application of this method for fabricating crack-free
      functional structures is demonstrated by producing crack-free Bragg reflectors
      that exhibit structural color.

PMID- 22984891
TI  - Editorial comment: Critical role of prostate biopsy mortality in the number of
      years of life gained and lost within a prostate cancer screening programme.

PMID- 22984892
TI  - Hydrocarbon-degrading potential of microbial communities from Arctic plants.
AB  - AIMS: To explore rhizospheric microbial communities from Arctic native plant
      species evaluating their bacterial hydrocarbon-degrading capacities. METHODS AND
      RESULTS: Eriophorum scheuchzeri, Potentilla cf. rubricaulis, Oxyria digyna, Salix
      arctica and Puccinellia angustata plant species were collected at Eureka
      (Canadian high Arctic) along with their rhizospheric soil samples. Their
      bacterial community fingerprints (16S rRNA gene, DGGE) were distinctive
      encompassing members from the phyla: Bacteroidetes, Firmicutes, Actinobacteria
      and Proteobacteria. Isolated diesel-degrading bacteria belonged to the phyla
      Actinobacteria and Proteobacteria. Strains of Mycobacterium, Nocardia,
      Rhodococcus, Intrasporangiaceae, Leifsoni and Arthrobacter possessed alkB and
      Pseudomonas possessed both ndoB and xylE gene sequences. Two Rhodococcus strains
      mineralized [1-(14) C] hexadecane at 5 and -5 degrees C. From the rhizosphere of
      P. angustata, larger numbers of hydrocarbon-degrading bacteria were isolated than
      from other plant rhizosphere samples and all three genes alkB (from
      Actinobacteria), ndoB and xylE (from Pseudomonas) were detected by PCR.
      CONCLUSIONS: (i) Arctic plants have unique rhizospheric bacterial communities.
      (ii) P. angustata has potential for phytoremediation research at high Arctic
      soils. (iii) Isolated bacteria mineralized hydrocarbons at ambient low
      temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge,
      this is the first rhizospheric exploration examining the phytoremediation
      potential of five Arctic plants and evaluating their microbial hydrocarbon
      degrading capacities.

PMID- 22984893
TI  - A gluten-free diet effectively reduces symptoms and health care consumption in a
      Swedish celiac disease population.
AB  - BACKGROUND: A gluten-free diet is the only available treatment for celiac
      disease. Our aim was to investigate the effect of a gluten-free diet on celiac
      disease related symptoms, health care consumption, and the risk of developing
      associated immune-mediated diseases. METHODS: A questionnaire was sent to 1,560
      randomly selected members of the Swedish Society for Coeliacs, divided into equal
      sized age- and sex strata; 1,031 (66%) responded. Self-reported symptoms, health
      care consumption (measured by health care visits and hospitalization days), and
      missed working days were reported both for the year prior to diagnosis (normal
      diet) and the year prior to receiving the questionnaire while undergoing
      treatment with a gluten-free diet. Associated immune-mediated diseases (diabetes
      mellitus type 1, rheumatic disease, thyroid disease, vitiligo, alopecia areata
      and inflammatory bowel disease) were self-reported including the year of
      diagnosis. RESULTS: All investigated symptoms except joint pain improved after
      diagnosis and initiated gluten-free diet. Both health care consumption and missed
      working days decreased. Associated immune-mediated diseases were diagnosed
      equally often before and after celiac disease diagnosis. CONCLUSIONS: Initiated
      treatment with a gluten-free diet improves the situation for celiac disease
      patients in terms of reduced symptoms and health care consumption. An earlier
      celiac disease diagnosis is therefore of great importance.

PMID- 22984894
TI  - Systematic review of computer-navigated total knee arthroplasty.
AB  - BACKGROUND: Conventional total knee arthroplasty (TKA) and the more recently
      available computer-navigated total knee arthroplasty (CNTKA) use alternative
      methods to achieve correct limb alignment. This systematic review was undertaken
      to assess the safety and effectiveness of CNTKA compared with conventional TKA.
      METHODS: A systematic search of multiple databases identified relevant randomized
      controlled trials published to August 2012. Study inclusion was established
      through application of a predetermined protocol, with independent assessment by
      two reviewers. RESULTS: Thirty randomized controlled trials were included. The
      majority of adverse events associated with CNTKA were minor and comparable with
      those seen with conventional TKA. Conversion to conventional TKA was required in
      1% of patients undergoing CNTKA. Thirteen trials reporting on satisfactory post
      operative radiological alignment of the mechanical axis in the frontal plane were
      suitable for meta-analysis, which showed a significant total odds ratio (non
      event) of 2.32 (95% confidence interval: 1.77-3.04) in favour of CNTKA (P <
      0.00001). Clinical outcomes were comparable between the two techniques, with
      longer-term follow-up suggesting that CNTKA provided no benefit over conventional
      TKA in terms of sustained functional improvements. CONCLUSIONS: At present, it is
      unclear whether the significant improvements shown in radiological outcomes after
      CNTKA translate to measurable clinical benefits. Although an assumption could be
      made that an improvement in post-operative alignment should lead to an
      improvement in patient-related outcomes, the available literature did not clearly
      show this. Further, long-term trials are required to address this issue.

PMID- 22984895
TI  - Seasonal and vertical distribution of putative ammonia-oxidizing thaumarchaeotal
      communities in an oligotrophic lake.
AB  - The discovery of Archaea carrying an amoA gene coding for the A-subunit of
      ammonia monooxygenase gave a boost to studies aimed at detecting this gene under
      diverse conditions. Despite numerous studies describing the archaeal amoA gene
      abundance and richness in different habitats, the understanding of the freshwater
      ecology of potentially archaeal ammonia oxidizers, recently positioned in the
      phylum Thaumarchaeota, is still lacking. In a seasonal and vertical study of deep
      oligotrophic Lake Lucerne, Switzerland, with high Thaumarchaeota-specific
      crenarchaeol concentrations, we showed that all archaeal 16S rRNA genes found
      belong to the thaumarchaeotal phylum. The abundances of archaeal 16S rRNA and
      amoA genes remained in the same order of magnitude (average 6 * mL(-1) ) and
      displayed matching seasonal dynamics within 16 monthly collected samples at three
      different water depths (r(2)  = 0.80, slope of 1.06). The Thaumarchaeota in this
      lake form a distinct cluster in both the 16S rRNA and amoA gene phylogenies, are
      affiliated to other thaumarchaeotal freshwater sequences within group 1.1a
      Archaea, and fall in the low saline cluster of the amoA phylogeny. In accordance
      with temperature and conductivity, the Thaumarchaeota in the surface water showed
      a significantly different seasonality and lower abundance than their counterparts
      in the deeper waters. This study indicates that the ecology of Thaumarchaeota,
      with their potential in nitrogen cycling, may differ per water depth in deep
      freshwater ecosystems.

PMID- 22984896
TI  - Long-lasting pro-ictogenic effects induced in vivo by rat brain exposure to serum
      albumin in the absence of concomitant pathology.
AB  - PURPOSE:   Dysfunction of the blood-brain barrier (BBB) is a common finding
      during seizures or following epileptogenic brain injuries, and experimentally
      induced BBB opening promotes seizures both in naive and epileptic animals. Brain
      albumin extravasation was reported to promote hyperexcitability by inducing
      astrocytes dysfunction. To provide in vivo evidence for a direct role of
      extravasated serum albumin in seizures independently on the pathologic context,
      we did the following: (1) quantified the amount of serum albumin extravasated in
      the rat brain parenchyma during status epilepticus (SE); (2) reproduced a similar
      concentration in the hippocampus by intracerebroventricular (i.c.v.) albumin
      injection in naive rats; (3) measured electroencephalography (EEG) activity in
      these rats, their susceptibility to kainic acid (KA)-induced seizures, and their
      hippocampal afterdischarge threshold (ADT). METHODS:   Brain albumin
      concentration was measured in the rat hippocampus and other forebrain regions 2
      and 24 h after SE by western blot analysis. Brain distribution of serum albumin
      or fluorescein isothiocyanate (FITC)-albumin was studied by immunohistochemistry
      and immunofluorescence, respectively. Naive rats were injected with rat albumin
      or FITC-albumin, i.c.v., to mimic the brain concentration attained after SE, or
      with dextran used as control. Inflammation was evaluated by immunohistochemistry
      by measuring glial induction of interleukin (IL)-1beta. Western blot analysis was
      used to measure inward rectifying potassium channel subunit Kir4.1 protein levels
      in the hippocampus. Seizures were induced in rats by intrahippocampal injection
      of 80 ng KA and quantified by EEG analysis, 2 or 24 h after rat albumin or
      dextran administration. ADT was measured by electrical stimulation of the
      hippocampus 3 months after albumin injection. In these rats, EEG was continuously
      monitored for 2 weeks to search for spontaneous seizures. KEY FINDINGS:   The
      hippocampal serum albumin concentration 24 h post-SE was 0.76 +/- 0.21 MUm.
      Similar concentrations were measured in other forebrain regions, whereas no
      changes were found in cerebellum. The hippocampal albumin concentration was
      similarly reproduced in naive rats by i.c.v. administration of 500 MUg/4 MUl rat
      albumin: albumin was predominantly detected extracellularly 2 h after injection,
      whereas at 24 h it was visible inside pyramidal neurons and in only a few
      scattered chondroitin sulphate proteoglycan (NG2)-positive cells, but not in
      glial fibrillary acidic protein (GFAP)-positive astrocytes or CR-3 complement
      receptor (OX-42)-positive microglia. The presence of albumin in naive rat
      hippocampus was associated with induced IL-1beta in GFAP-positive astrocytes and
      a concomitant tissue down-regulation of Kir4.1. Spiking activity was evoked by
      albumin in the hippocampus lasting for 2 h. When KA was intrahippocampally
      applied either 2 or 24 h after albumin injection, the number of total interictal
      spikes in 3 h EEG recording was significantly increased by twofold on average.
      Three months after albumin injection, neither albumin nor inflammation was
      detected in brain tissue; at this time, the ADT was reduced by 50% but no
      spontaneous seizures were observed. SIGNIFICANCE:   Transient hippocampal
      exposure to albumin levels similar to those attained after prominent BBB
      breakdown resulted in increased seizure susceptibility and long-term reduction in
      seizure threshold, but it did not evoke spontaneous seizures. These effects may
      be mediated by albumin-induced astrocytes dysfunction and the associated
      induction of proinflammatory molecules.

PMID- 22984897
TI  - Using educational outreach and a financial incentive to increase general
      practices' contribution to chlamydia screening in South-East London 2003-2011.
AB  - BACKGROUND: The London Boroughs of Lambeth and Southwark have high levels of
      sexually transmitted infections including Chlamydia trachomatis. Modelling
      studies suggest that reductions in the prevalence of chlamydia infection will
      require a high level of population screening coverage and positivity among those
      screened. General practice has a potentially important role to play in delivering
      these levels of coverage since large numbers (up to 60%) of young people visit
      their general practice every year but previous work suggests that there are
      barriers to delivering screening in this setting. The aim of this study was to
      evaluate an intervention to increase chlamydia screening in general practice
      within Primary Care Trusts (PCTs) of Lambeth and Southwark, a strategy combining
      financial incentives and supportive practice visits to raise awareness and solve
      problems. METHODS: Data on age, gender, venue and chlamydia result for tests on
      under 25 s in Lambeth from 2003-11 was obtained from the National Chlamydia
      Screening Programme. We analysed the number and percentage of tests generated in
      general practice, and looked at the number of practices screening more than 10%
      of their practice cohort of 15-24 year olds, male/female ratio and positivity
      rates across other screening venues. We also looked at practices screening less
      than 10% and studied change over time. We compared data from Lambeth and
      Southwark with London and England. We also studied features of the level and type
      of educational and financial incentive interventions employed. RESULTS: Chlamydia
      tests performed in general practice increased from 23 tests in 2003-4 to 4813
      tests in 2010-11 in Lambeth. In Southwark they increased from 5 tests in 2003/04
      to 4321 in 2010/11. In 2011, 44.6% of tests came from GPs in Lambeth and 46% from
      GP's in Southwark. In Lambeth 62.7% of practices tested more than 10% of their
      cohort and in Southwark this was 55.8%. In Lambeth, postivity rate in 2010/11 was
      5.8% in men and 6.0% in women. In Southwark positivity rate was 3.9% in men and
      5.3% in women. In 2003/04 13% tests in general practice (Lambeth) were from men,
      this increased to 25% in 2010/11. In Southwark this increased from 20% in 2003/04
      to 27.6% in 2010/11. We compared the results with London and national data and
      showed significant differences between GP testing in Lambeth and Southwark, and
      GP testing in London and the rest of England. CONCLUSIONS: General practices can
      be important potential providers of chlamydia tests.With a combination of
      sustained support, financial incentives and feedback on performance, general
      practice may be able to test a large percentage of 15-24 year olds. General
      practice is also a potentially important provider of chlamydia tests to young
      men.

PMID- 22984899
TI  - Stones lodge at three sites of anatomic narrowing in the ureter: clinical fact or
      fiction?
AB  - Abstract Background and Purpose: Throughout the literature, the ureter is
      described as having three anatomic sites of narrowing at which kidney stones
      typically become lodged: The ureteropelvic junction (UPJ), the ureteral crossing
      of the iliac vessels, and the ureterovesical junction (UVJ). There is little
      evidence to support this notion, however. The purpose of our study is to evaluate
      whether three peaks in stone distribution corresponding to these anatomic
      landmarks exist. METHODS: We retrospectively reviewed the kidneys-ureters-bladder
      (KUB) films of 622 patients with solitary ureteral calculi referred for shockwave
      lithotripsy (SWL). Pretreatment KUB films were used to categorize the location of
      their ureteral stone relative to 1 of 19 levels referenced to the axial skeleton.
      CT scans of 74 patients were used to determine the location of the UPJ, ureteral
      crossing of the iliac vessels, and UVJ relative to the 19 levels on KUB
      radiography. Histograms were then constructed to plot the distribution of stones
      within the ureter relative to these 19 levels. The effect of sex, stone size and
      side, and presence of a stent on stone distribution were analyzed. RESULTS: There
      are two peaks in the distribution of stones within the ureter in patients
      referred for SWL that correspond to the UPJ/proximal ureter and intramural
      ureter/UVJ. In patients with larger stones (>=100 mm(2)) or a ureteral stent in
      place, stones were distributed more proximally (P<0.0001). When comparing sexes,
      there was a difference in stone distribution that approached significance
      (P=0.0523), with a greater peak more distally in males compared with females.
      CONCLUSIONS: Our review demonstrates a peak in the distribution of stones
      corresponding to the UPJ/proximal ureter and the intramural ureter/UVJ. We failed
      to demonstrate a peak in stone distribution corresponding with the ureteral
      crossing of the iliac vessels.

PMID- 22984898
TI  - Energy filtering transmission electron microscopy immunocytochemistry and antigen
      retrieval of surface layer proteins from Tannerella forsythensis using microwave
      or autoclave heating with citraconic anhydride.
AB  - Tannerella forsythensis (Bacteroides forsythus), an anaerobic Gram-negative
      species of bacteria that plays a role in the progression of periodontal disease,
      has a unique bacterial protein profile. It is characterized by two unique protein
      bands with molecular weights of more than 200 kDa. It also is known to have a
      typical surface layer (S-layer) consisting of regularly arrayed subunits outside
      the outer membrane. We examined the relationship between high molecular weight
      proteins and the S-layer using electron microscopic immunolabeling with chemical
      fixation and an antigen retrieval procedure consisting of heating in a microwave
      oven or autoclave with citraconic anhydride. Immunogold particles were localized
      clearly at the outermost cell surface. We also used energy-filtering transmission
      electron microscopy (EFTEM) to visualize 3, 3'-diaminobenzidine
      tetrahydrochloride (DAB) reaction products after microwave antigen retrieval with
      1% citraconic anhydride. The three-window method for electron spectroscopic
      images (ESI) of nitrogen by the EFTEM reflected the presence of moieties
      demonstrated by the DAB reaction with horseradish peroxidase (HRP)-conjugated
      secondary antibodies instead of immunogold particles. The mapping patterns of net
      nitrogen were restricted to the outermost cell surface.

PMID- 22984900
TI  - Practical method for the Cu-mediated trifluoromethylation of arylboronic acids
      with CF3 radicals derived from NaSO2CF3 and tert-butyl hydroperoxide (TBHP).
AB  - A mild and practical protocol for the copper-mediated trifluoromethylation of
      aryl and heteroaryl boronic acids using NaSO(2)CF(3) (Langlois' reagent) and TBHP
      is described. The reaction proceeds at room temperature under ambient conditions,
      and the products can be readily purified by extraction or column chromatography.

PMID- 22984901
TI  - Low-temperature aluminum reduction of graphene oxide, electrical properties,
      surface wettability, and energy storage applications.
AB  - Low-temperature aluminum (Al) reduction is first introduced to reduce graphene
      oxide (GO) at 100-200  degrees C in a two-zone furnace. The melted Al metal
      exhibits an excellent deoxygen ability to produce well-crystallized reduced
      graphene oxide (RGO) papers with a low O/C ratio of 0.058 (Al-RGO), compared with
      0.201 in the thermally reduced one (T-RGO). The Al-RGO papers possess outstanding
      mechanical flexibility and extremely high electrical conductivities (sheet
      resistance R(s) ~ 1.75 Omega/sq), compared with 20.12 Omega/sq of T-RGO. More
      interestingly, very nice hydrophobic nature (90.5 degrees ) was observed,
      significantly superior to the reported chemically or thermally reduced papers.
      These enhanced properties are attributed to the low oxygen content in the RGO
      papers. During the aluminum reduction, highly active H atoms from H(2)O reacted
      with melted Al promise an efficient oxygen removal. This method was also
      applicable to reduce graphene oxide foams, which were used in the GO/SA (stearic
      acid) composite as a highly thermally conductive reservoir to hold the phase
      change material for thermal energy storage. The Al-reduced RGO/SnS(2) composites
      were further used in an anode material of lithium ion batteries possessing a
      higher specific capacity. Overall, low-temperature Al reduction is an effective
      method to prepare highly conductive RGO papers and related composites for
      flexible energy conversion and storage device applications.

PMID- 22984903
TI  - Cancer is part of the lymphatic continuum.

PMID- 22984902
TI  - Selective fluorescent nonpeptidic antagonists for vasopressin V2 GPCR:
      application to ligand screening and oligomerization assays.
AB  - A series of fluorescent benzazepine ligands for the arginine-vasopressin V2
      receptor (AVP V2R) was synthesized using "Click" chemistry. Their in vitro
      pharmacological profile at AVP V2R, V(1a)R, V(1b)R, and oxytocin receptor was
      measured by binding assay and functional studies. Compound 9p, labeled with
      Lissamine Rhodamine B using novel solid-phase organic tagging (SPOrT) resin,
      exhibited a high affinity for V2R (4.0 nM), an excellent selectivity toward V2R
      and antagonist properties. By changing the nature of the dye, DY647 and Lumi4-Tb
      probes 44 and 47 still display a high affinity for V2R (5.6 and 5.8 nM,
      respectively). These antagonists constitute the first high-affinity selective
      nonpeptidic fluorescent ligands for V2R. They enabled the development of V2R time
      resolved FRET-based assay readily amenable to high-throughput screening. Taking
      advantage of their selectivity, these compounds were also successfully involved
      in the study of V(1a)R-V2R dimerization on cell surface.

PMID- 22984904
TI  - Lymphatic vessels and cancer.

PMID- 22984906
TI  - A quantitative examination of lymph drainage from perilesion skin in human
      melanoma.
AB  - BACKGROUND: An increase in lymph flow from melanomas to draining lymph nodes has
      been reported in animal studies. It has been postulated that this contributes to
      metastatic potential of cancers. Data from animal studies are not easily
      extrapolated to humans; animal studies use immunosuppressed animals modified to
      overexpress lymphangiogenic growth factors, injected with human tumor cell lines,
      or manipulated to develop aggressive tumors. Human studies are required to
      investigate lymph flow in humans with cancers such as melanoma. METHODS AND
      RESULTS: The present study aims to quantify the removal rate constant k (a
      measure of local lymph flow per unit volume of distribution of the radiotracer)
      from the vicinity of melanomas, benign nevi, and normal skin in humans in vivo
      using quantitative lymphoscintigraphy (QL). 16 patients with pigmented lesions
      underwent QL to quantify k near the lesion (k(perilesion)) and in contralateral
      matched normal skin (k(control)). The lesions were then excised and, based on
      histological outcome, the patients were divided into two groups: benign nevus
      (n=9) and melanoma (n=7). There was no difference between k(perilesion) and
      k(control) in either the benign naevus (p=0.29, paired t test) or the melanoma
      group (p=0.93). k(perilesion) in melanomas (0.233+/-0.123% min(-1)) was not
      increased relative to k(perilesion) in benign nevi (0.376+/-0.231% min(-1),
      p=0.16, unpaired t test). CONCLUSIONS: We found no evidence for increased
      lymphatic drainage in melanoma relative to benign nevi or normal matched skin in
      humans.

PMID- 22984907
TI  - Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.
AB  - There are controversial views as to whether intratumoral or peritumoral
      lymphatics play a dominant role in the metastatic process. Most clinical
      observations originate from studies of colon cancer. Colon contains mucosa and
      submucosa rich in lymphatics and with high lymph formation rate. This seems to be
      a prerequisite for easy metastasis of cancer cells to regional lymph nodes.
      However, there are other tissues as pancreas with a rudimentary lymphatic network
      where cancer metastasis formation is as intensive as in colon cancer. This
      contradicts the common notion that intratumor lymphatics play major role in
      metastases. We visualized interstitial space and lymphatics in the central and
      peripheral regions of colon and pancreas tumors using the color stereoscopic
      lymphography and simultaneously immunohistochemical performed stainings specific
      for lymphatic and blood endothelial cells. The density of open and compressed
      lymphatic and blood vessels was measured in the tumor core and edge. There were
      very few lymphatics in the colon and pancreas tumor core but numerous minor fluid
      "lakes" with no visible connection to the peritumoral lymphatics. Lining of
      "lakes" did not express molecular markers specific for lymphatic endothelial
      cells. Dense connective tissue surrounding tumor foci did not contain lymphatics.
      Peritumoral lymphatics were irregularly distributed in both types of tumor and
      only sporadically contained cells that might be tumor cells. Similar
      lymphoscintigraphic and histological pictures were seen in colon and pancreas
      cancer despite of different structure of both tissues. This suggests a uniform
      reaction of tissues to the growing cancer irrespective of the affected organ.

PMID- 22984908
TI  - Multiple inguinal and pelvic lymph node metastases of malignant melanoma of the
      heel identified by common iliac lymphadenopathy.
AB  - It is extremely rare that swelling of pelvic lymph nodes is found when inguinal
      lymph nodes contain only a microscopic amount of disease without enlargement. A
      69-year-old woman with malignant melanoma of the heel was treated with a wide,
      local excision. About four years after the initial operation, a left common iliac
      node was enlarged although all lymph nodes in the obturator, external iliac and
      inguinal regions were not enlarged. Rapid pathological examination of the
      resected swollen lymph nodes revealed involvement of malignant melanoma, and left
      pelvic and groin dissection was undertaken. Histologically, multiple lymph node
      metastases were found in the common iliac, obturator, external iliac and inguinal
      regions. This case indicates that sentinel lymph node biopsy may be worth
      considering even for stage IA malignant melanoma of the lower extremity.

PMID- 22984905
TI  - The role of sphingosine-1-phosphate in breast cancer tumor-induced
      lymphangiogenesis.
AB  - Sphingosine-1-phosphate (S1P) is a potent sphingolipid metabolite that regulates
      a number of biological processes critical for cancer. S1P produced inside cancer
      cells is exported and exerts its extracellular functions by binding to its
      specific receptors in an autocrine, paracrine, and/or endocrine manner, which is
      known as inside-out signaling. S1P is also known to exert its intracellular
      functions especially in the inflammatory process, but its relevance to cancer
      biology remains to be elucidated. Recently, there have been growing interests in
      the role of S1P in breast cancer progression, including angiogenesis and
      lymphangiogenesis. Our group demonstrated that activation of sphingosine kinase
      1, the enzyme that catalyzes the phosphorylation of sphingosine to S1P, is a key
      step of this process. In this review, we will cover our current knowledge on the
      role of S1P signaling pathway in breast cancer progression with an emphasis on
      its role in tumor-induced lymphangiogenesis.

PMID- 22984909
TI  - Increased hyaluronan expression at distinct time points in acute lymphedema.
AB  - Lymphatic dysfunction in lymphedema results in chronic accumulation of
      interstitial fluid and life-long tissue swelling. In the absence of restored
      lymphatic drainage via adequate lymphangiogenesis, the interstitial environment
      can remodel in ways that decrease the elevated interstitial stress. Presently,
      relatively little is known about the glycosaminoglycans (GAGs) that become
      upregulated in the interstitium during lymphedema. We employed a mouse tail model
      of acute lymphedema that reproduces important features of the chronic human
      condition to establish a relationship between hyaluronan (HA) and sulfated GAG
      concentration with tissue swelling. We found that HA was upregulated by tissue
      injury at day 5 and became upregulated again by skin swelling (HA content
      increasing by 27% relative to controls at days 15 and 20). Surprisingly, the
      second phase of HA expression was associated with the declining phase of the tail
      skin swelling (tail diameter significantly decreasing by 17% from day 10 peak to
      day 20), demonstrating that HA is upregulated by tissue swelling and may help to
      counteract the edema in the mouse tail. This finding was confirmed by intradermal
      injection of an HA degrading enzyme (hyaluronidase) to the swollen tail, which
      was found to worsen the tail swelling. Sulfated GAGs, including chondroitin
      sulfate (CS), were not regulated by tissue swelling. The results demonstrate that
      HA, but not sulfated GAGs, is upregulated in the interstitium by acute tissue
      swelling. We speculate that HA expression during lymphedema may be part of a
      natural adaptive mechanism of the interstitial environment to reduce capillary
      filtration and increase interstitial fluid outflow following lymphatic
      obstruction and fluid accumulation.

PMID- 22984910
TI  - Comparison of intermittent pneumatic compression with manual lymphatic drainage
      for treatment of breast cancer-related lymphedema.
AB  - BACKGROUND: The aim of this prospective controlled study was to assess the
      efficacy of two different combination treatment modalities of lymphedema (LE).
      Manual lymphatic drainage (MLD) and compression bandage combination (complex
      decongestive therapy) have been compared with intermittent pneumatic compression
      (IPC) plus self-lymphatic drainage (SLD). METHODS AND RESULTS: Both MLD with
      compression bandage (complex decongestive therapy) group (Group I, n=15) and IPC
      with SLD group (Group II, n=15) received treatment for LE 3 days in a week and
      every other day for 6 weeks. Arm circumferences were measured before and the 1st,
      3rd, and 6th weeks of the treatment. EORTC-QLQ and ASES-tests were performed to
      assess the quality of life before and after 6 week-treatment. Patients in both
      groups had similar demographic and clinical characteristics. Even though both
      treatment modalities resulted in significant decrease in the total arm volume
      (12.2% decrease in Group II and 14.9% decrease in Group I) (p<0.001), no
      significant difference (p=0.582) was found between those two groups. Similarly,
      ASES scores were significantly (p=0.001) improved in both Group I and II without
      any significant difference between the groups. While emotional functioning,
      fatigue, and pain scores were significantly improved in both groups, global
      health status, functional and cognitive functioning scores appeared to be
      improved only in patients of group I. CONCLUSIONS: Different treatment modalities
      consisting of MLD and compression bandage(complex decongestive therapy) or IPC
      and SLD appear to be effective in the treatment of LE with similar therapeutic
      efficacy in patients with breast cancer. However, combination modalities
      including IPC and SLD may be the preferred choices for their applicability at
      home.

PMID- 22984914
TI  - Economic evaluation of vampire bat (Desmodus rotundus) rabies prevention in
      Mexico.
AB  - Vampire bat rabies causes significant impacts within its endemic range in Mexico.
      These impacts include livestock mortality, animal testing costs, post-exposure
      prophylaxis costs, and human mortality risk. Mitigation of the impacts can be
      achieved by vaccinating livestock and controlling vampire bat populations. A
      benefit-cost analysis was performed to examine the economic efficiency of these
      methods of mitigation, and Monte Carlo simulations were used to examine the
      impact that uncertainty has on the analysis. We found that livestock vaccination
      is efficient, with benefits being over six times higher than costs. However, bat
      control is inefficient because benefits are very unlikely to exceed costs. It is
      concluded that when these mitigation methods are judged by the metric of economic
      efficiency, livestock vaccination is desirable but bat control is not. 

PMID- 22984915
TI  - Sexual selection and experimental evolution of chemical signals in Drosophila
      pseudoobscura.
AB  - Our expectations for the evolution of chemical signals in response to sexual
      selection are uncertain. How are chemical signals elaborated? Does sexual
      selection result in complexity of the composition or in altered quantities of
      expression? We addressed this in Drosophila pseudoobscura by examining male and
      female cuticular hydrocarbons (CHs) after 82 generations of elevated (E) sexual
      selection or relaxed sexual selection through monogamy (M). The CH profile
      consisted of 18 different components. We extracted three eigenvectors using
      principal component analysis that explained 72% of the variation. principal
      component (PC)1 described the amount of CHs produced, PC2 the trade-off between
      short- and long-chain CHs and PC3 the trade-off between apparently arbitrary CHs.
      In both sexes, the amount of CHs produced was greater in flies from the E
      treatment. PC3 was also higher, indicating that sexual selection also influenced
      the evolution of CH composition. The sexes differed in all three PCs, indicating
      substantial sexual dimorphism in this species, although the magnitude of this
      dimorphism was not increased as a result of our experimental evolution.
      Collectively, our work provides direct evidence that sexual selection plays an
      important role in the evolution of CHs in D. pseudoobscura and that both
      increased quantity and overall composition are targeted.

PMID- 22984913
TI  - Aging mechanism of soman inhibited acetylcholinesterase.
AB  - Acetylcholinesterase (AChE) is a crucial enzyme in the cholinergic nervous system
      that hydrolyzes neurotransmitter acetylcholine (ACh) and terminates synaptic
      signals. The catalytic serine of AChE can be phosphonylated by soman, one of the
      most potent nerve agents, and subsequently undergo an aging reaction. This
      phosphonylation and aging process leads to irreversible AChE inhibition, results
      in accumulation of excess ACh at the synaptic clefts, and causes neuromuscular
      paralysis. By employing Born-Oppenheimer ab initio QM/MM molecular dynamics
      simulations with umbrella sampling, a state-of-the-art approach to simulate
      enzyme reactions, we have characterized the aging mechanism of soman
      phosphonylated AChE and determined its free energy profile. This aging reaction
      starts with the scission of the O2-Calpha bond, which is followed by methyl
      migration, and results in a tertiary carbenium intermediate. At the transition
      state, the scissile O2-Calpha bond is already cleaved with an average O-C
      distance of 3.2 +/- 0.3 A and the migrating methyl group is shared between Calpha
      and Cbeta carbons with C-C distances of 1.9 +/- 0.1 and 1.8 +/- 0.1 A,
      respectively. The negatively charged phosphonate group is stabilized by a salt
      bridge with the imidazole ring of the catalytic histidine. A major product of
      aging, 2,3-dimethyl-2-butanol can be formed swiftly by the reaction of a water
      molecule. Our characterized mechanism and simulation results provide new detailed
      insights into this important biochemical process.

PMID- 22984917
TI  - Complete denture occlusion: an evidence-based approach.
AB  - PURPOSE: This study involved an extensive search for randomized controlled
      clinical trials comparing bilateral balanced and canine-guided dentures, and
      questioned whether a bilateral balanced occlusion is imperative for successful
      denture treatment. MATERIALS AND METHODS: Studies were identified by searching
      electronic databases (PubMed/MEDLINE, ISI Web of Science, LILACS, and BBD). The
      keywords "denture" and "occlusion" were used. The minimum inclusion requirements
      were (1) randomized controlled trials with patients of any age wearing both
      maxillary and mandibular conventional complete dentures (CDs), (2) comparison
      between bilateral balanced and canine-guided dentures, and (3) assessment of
      masticatory function and/or patients' satisfaction. RESULTS: The search resulted
      in the identification of 5166 articles. Subsequently, 5156 articles were excluded
      on the basis of title and abstract. By the end of the search phase, seven
      randomized controlled trials were considered eligible. CONCLUSIONS: Current
      scientific evidence suggests that bilateral balanced occlusion is not imperative
      for successful treatment with conventional CDs in average patients. More studies
      are necessary to identify if specific clinical conditions may benefit from a
      balanced occlusion.

PMID- 22984916
TI  - Simplified equation to extract diffusion coefficients from confocal FRAP data.
AB  - Quantitative measurements of diffusion can provide important information about
      how proteins and lipids interact with their environment within the cell and the
      effective size of the diffusing species. Confocal fluorescence recovery after
      photobleaching (FRAP) is one of the most widely accessible approaches to measure
      protein and lipid diffusion in living cells. However, straightforward approaches
      to quantify confocal FRAP measurements in terms of absolute diffusion
      coefficients are currently lacking. Here, we report a simplified equation that
      can be used to extract diffusion coefficients from confocal FRAP data using the
      half time of recovery and effective bleach radius for a circular bleach region,
      and validate this equation for a series of fluorescently labeled soluble and
      membrane-bound proteins and lipids. We show that using this approach, diffusion
      coefficients ranging over three orders of magnitude can be obtained from confocal
      FRAP measurements performed under standard imaging conditions, highlighting its
      broad applicability.

PMID- 22984919
TI  - Structure-property relationships in solid solutions of noncentrosymmetric
      Aurivillius phases, Bi(4-x)La(x)Ti3O12 (x = 0-0.75).
AB  - Solid solutions of the noncentrosymmetric (NCS) Aurivillius phases, Bi(4
      x)La(x)Ti(3)O(12) (x = 0, 0.25, 0.50, 0.75), have been synthesized through
      standard solid-state reactions and structurally characterized by powder X-ray and
      neutron diffractions. These materials crystallize in the orthorhombic space group
      B2cb (No. 41) and exhibit layered perovskite structures with both (Bi(2)O(2))(2+)
      fluorite-like units and [A(n-1)B(n)O(3n+1)](2-) (n = 3) blocks. As the amount of
      La(3+) cations increases, the polarization arising from the Bi(3+) positions,
      especially the A sites of the perovskite units, continuously decreases in the
      reported materials. Powder second-harmonic generation (SHG) measurements on  Bi(4
      x)La(x)Ti(3)O(12) using 1064 nm radiation revealed frequency-doubling
      efficiencies ranging from 200 to 50 times that of alpha-SiO(2). Converse
      piezoelectric measurements resulted in d(33) values of 19 and 13 pm V(-1) for
      Bi(4)Ti(3)O(12) and Bi(3.5)La(0.5)Ti(3)O(12), respectively. The magnitudes of the
      SHG efficiency and piezoelectric response are strongly dependent on the
      asymmetric coordination environment attributable to the lone pairs on Bi(3+).
      Structure-property relationships along with the influence of the doped foreign
      cation on the associated NCS properties are discussed.

PMID- 22984918
TI  - Case report: sequelae of traumatic reticuloperitonitis in a Friesian dairy cow.
AB  - CASE HISTORY: A 10-year-old Friesian dairy cow presented with a history of weight
      loss, decreased milk production and fluid splashing on auscultation of the heart.
      Previous antibiotic therapy included oxytetracycline, marbofloxacin and
      penicillin. CLINICAL AND PATHOLOGICAL FINDINGS: Following a failure to respond to
      treatment, prescribed by the referring veterinarian for respiratory infection and
      septic arthritis, the cow was referred to Massey University Veterinary Teaching
      Hospital with suspected pericarditis. Clinical examination identified a
      predominantly left sided holodiastolic heart murmur with tachycardia and cording
      of the jugular veins. Cardiac ultrasound showed an enlarged aortic valve with
      turbulent blood flow and regurgitation, consistent with bacterial endocarditis.
      Blood culture demonstrated Paenibacillus spp. Due to the severity of the clinical
      signs and poor prognosis, euthanasia was performed and a post-mortem examination
      carried out. DIAGNOSIS: Traumatic reticuloperitonitis with abscessation of the
      reticulum and rumen wall, which progressed to a bacteraemia and presumptively
      caused endocarditis, endometritis, septic arthritis, and renal and myocardial
      infarcts due to emboli from the endocarditis lesions. CLINICAL RELEVANCE: New
      Zealand dairy cattle are at risk of traumatic reticuloperitonitis and due to
      varying presentations diagnosis can be complicated. Subsequent bacteraemia is
      common and in this case the novel bacterial species Paenibacillus was implicated
      as a potential pathogen.

PMID- 22984920
TI  - Geographical accessibility and spatial coverage modeling of the primary health
      care network in the Western Province of Rwanda.
AB  - BACKGROUND: Primary health care is essential in improving and maintaining the
      health of populations. It has the potential to accelerate achievement of the
      Millennium Development Goals and fulfill the "Health for All" doctrine of the
      Alma-Ata Declaration. Understanding the performance of the health system from a
      geographic perspective is important for improved health planning and evidence
      based policy development. The aims of this study were to measure geographical
      accessibility, model spatial coverage of the existing primary health facility
      network, estimate the number of primary health facilities working under capacity
      and the population underserved in the Western Province of Rwanda. METHODS: This
      study uses health facility, population and ancillary data for the Western
      Province of Rwanda. Three different travel scenarios utilized by the population
      to attend the nearest primary health facility were defined with a maximum
      travelling time of 60 minutes: Scenario 1--walking; Scenario 2--walking and
      cycling; and Scenario 3--walking and public transportation. Considering these
      scenarios, a raster surface of travel time between primary health facilities and
      population was developed. To model spatial coverage and estimate the number of
      primary health facilities working under capacity, the catchment area of each
      facility was calculated by taking into account population coverage capacity, the
      population distribution, the terrain topography and the travelling modes through
      the different land categories. RESULTS: Scenario 2 (walking and cycling) has the
      highest degree of geographical accessibility followed by Scenario 3 (walking and
      public transportation). The lowest level of accessibility can be observed in
      Scenario 1 (walking). The total population covered differs depending on the type
      of travel scenario. The existing primary health facility network covers only
      26.6% of the population in Scenario 1. In Scenario 2, the use of a bicycle
      greatly increases the population being served to 58% of inhabitants. When
      considering Scenario 3, the total population served is 34.3%. CONCLUSIONS:
      Significant spatial variations in geographical accessibility and spatial coverage
      were observed across the three travel scenarios. The analysis demonstrates that
      regardless of which travel scenario is used, the majority of the population in
      the Western Province does not have access to the existing primary health facility
      network. Our findings also demonstrate the usefulness of GIS methods to leverage
      multiple datasets from different sources in a spatial framework to provide
      support to evidence-based planning and resource allocation decision-making in
      developing countries.

PMID- 22984921
TI  - Avoidance but not aversion following sensory preconditioning with flavors: a
      challenge to stimulus substitution.
AB  - After two neutral stimuli have been paired (AB), directly conditioning a response
      to one of them (A) will also be reflected in a change in responding to the other
      (B). Standard accounts of this sensory preconditioning effect assume that it is
      mediated by a memory involving the stimulus that was directly conditioned (i.e.,
      A). The reliance on this shared pathway implies that sensory preconditioning
      (involving B) and direct conditioning (involving A) should support qualitatively
      similar patterns of responding. In three experiments, directly pairing A with
      lithium chloride (LiCl) delivery resulted in both a reduction in consumption of A
      (i.e., avoidance) and a reduction in the size of licking clusters it elicits
      (i.e., aversion). In contrast, the sensory preconditioning effect resulted in a
      reduction in the consumption of B but no change in the nature of the licking
      response that it elicited; and a similar dissociation was observed after trace
      conditioning. These dissociations involving direct conditioning and sensory
      preconditioning, observed over a range of flavor concentrations and different
      doses of LiCl, undermine standard accounts of sensory preconditioning that are
      based on the assumption of stimulus substitution.

PMID- 22984922
TI  - Location and salience of unique features in human perceptual learning.
AB  - Preexposure to intermixed presentations of a pair of similar stimuli (AX and BX,
      where A and B represent distinctive features, and X the features the stimuli hold
      in common) facilitates subsequent discrimination between them. This perceptual
      learning effect has been interpreted as indicating that the loss of effective
      salience resulting from repeated presentation of a stimulus is attenuated or
      reversed by a salience-modulation process that operates on the unique stimulus
      features A and B during intermixed preexposure. In 3 experiments, we examined
      discrimination after intermixed preexposure to AX and BX, making comparison with
      a condition in which novel unique features were added to the preexposed
      background (CX and DX). In all experiments, we also monitored eye gaze during
      both preexposure and the test. Experiments 1 and 2 found discrimination of the
      preexposed stimuli to be superior. This result cannot be explained by salience
      modulation theories that suppose that intermixed preexposure merely attenuates
      loss of salience to the unique features A and B; it suggests, rather, that
      intermixed preexposure to AX and BX enhances the salience of, or attention paid
      to, the distinctive features. Experiment 3 demonstrated that exposure increases
      sensitivity to the spatial location of the features, a conclusion confirmed by
      analysis of eye gaze.

PMID- 22984923
TI  - The role of convexity in perception of symmetry and in visual short-term memory.
AB  - Visual perception of shape is affected by coding of local convexities and
      concavities. For instance, a recent study reported that deviations from symmetry
      carried by convexities were easier to detect than deviations carried by
      concavities. We removed some confounds and extended this work from a detection of
      reflection of a contour (i.e., bilateral symmetry), to a detection of repetition
      of a contour (i.e., translational symmetry). We tested whether any convexity
      advantage is specific to bilateral symmetry in a two-interval (Experiment 1) and
      a single-interval (Experiment 2) detection task. In both, we found a convexity
      advantage only for repetition. When we removed the need to choose which region of
      the contour to monitor (Experiment 3) the effect disappeared. In a second series
      of studies, we again used shapes with multiple convex or concave features.
      Participants performed a change detection task in which only one of the features
      could change. We did not find any evidence that convexities are special in visual
      short-term memory, when the to-be-remembered features only changed shape
      (Experiment 4), when they changed shape and changed from concave to convex and
      vice versa (Experiment 5), or when these conditions were mixed (Experiment 6). We
      did find a small advantage for coding convexity as well as concavity over an
      isolated (and thus ambiguous) contour. The latter is consistent with the known
      effect of closure on processing of shape. We conclude that convexity plays a role
      in many perceptual tasks but that it does not have a basic encoding advantage
      over concavity.

PMID- 22984924
TI  - Gaps in the prevention of perinatal transmission of hepatitis B virus between
      recommendations and routine practices in a highly endemic region: a provincial
      population-based study in China.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is endemic in China; perinatal
      transmission is the main source of chronic HBV infection. Simultaneous
      administration of hepatitis B immune globulin (HBIG) and hepatitis B vaccine is
      highly effective to prevent perinatal transmission of HBV; however, the
      effectiveness also depends on full adherence to the recommended protocols in
      daily practice. In the present investigation, we aimed to identify gaps in
      immunoprophylaxis of perinatal transmission of HBV between recommendations and
      routine practices in Jiangsu Province, China. METHODS: Totally 626 children from
      6 cities and 8 rural areas across Jiangsu Province, China, born from February
      2003 to December 2004, were enrolled; 298 were born to mothers with positive
      hepatitis B surface antigen (HBsAg) and 328 were born to HBsAg-negative mothers.
      Immunoprophylactic measures against hepatitis B were retrospectively reviewed for
      about half of the children by checking medical records or vaccination cards and
      the vaccine status was validated for most of children. RESULTS: Of 298 children
      born to HBV carrier mothers, 11 (3.7%) were HBsAg positive, while none of 328
      children born to non-carrier mothers was HBsAg positive (P < 0.01). The rates of
      anti-HBs >= 10 mIU/ml in children of carrier and non-carrier mothers were 69.5%
      and 69.2% respectively (P = 0.95). The hepatitis B vaccine coverage in two groups
      was 100% and 99.4% respectively (P = 0.50), but 15.1% of HBV-exposed infants did
      not receive the timely birth dose. Prenatal HBsAg screening was performed only in
      156 (52.3%) of the carrier mothers. Consequently, only 112 (37.6%) of HBV-exposed
      infants received HBIG after birth. Furthermore, of the 11 HBV-infected children,
      only one received both HBIG and hepatitis B vaccine timely, seven missed HBIG,
      two received delayed vaccination, and one missed HBIG and received delayed
      vaccination. CONCLUSIONS: There are substantial gaps in the prevention of
      perinatal HBV infection between the recommendations and routine practices in
      China, which highlights the importance of full adherence to the recommendations
      to eliminate perinatal HBV infection in the endemic regions.

PMID- 22984926
TI  - A method to screen and evaluate tissue adhesives for joint repair applications.
AB  - BACKGROUND: Tissue adhesives are useful means for various medical procedures.
      Since varying requirements cause that a single adhesive cannot meet all needs,
      bond strength testing remains one of the key applications used to screen for new
      products and study the influence of experimental variables. This study was
      conducted to develop an easy to use method to screen and evaluate tissue
      adhesives for tissue engineering applications. METHOD: Tissue grips were designed
      to facilitate the reproducible production of substrate tissue and adhesive
      strength measurements in universal testing machines. Porcine femoral condyles
      were used to generate osteochondral test tissue cylinders (substrates) of
      different shapes. Viability of substrates was tested using PI/FDA staining. Self
      bonding properties were determined to examine reusability of substrates (n = 3).
      Serial measurements (n = 5) in different operation modes (OM) were performed to
      analyze the bonding strength of tissue adhesives in bone (OM-1) and cartilage
      tissue either in isolation (OM-2) or under specific requirements in joint repair
      such as filling cartilage defects with clinical applied fibrin/PLGA-cell
      transplants (OM-3) or tissues (OM-4). The efficiency of the method was determined
      on the basis of adhesive properties of fibrin glue for different assembly times
      (30 s, 60 s). Seven randomly generated collagen formulations were analyzed to
      examine the potential of method to identify new tissue adhesives. RESULTS:
      Viability analysis of test tissue cylinders revealed vital cells (>80%) in
      cartilage components even 48 h post preparation. Reuse (n = 10) of test substrate
      did not significantly change adhesive characteristics. Adhesive strength of
      fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3:
      32.7 kPa, OM-4: 30.1 kPa) and was increasing with assembly time on average (2.4
      fold). The screening of the different collagen formulations revealed a substance
      with significant higher adhesive strength on cartilage (14.8 kPa) and bone tissue
      (11.8 kPa) compared to fibrin and also considerable adhesive properties when
      filling defects with cartilage tissue (23.2 kPa). CONCLUSION: The method
      confirmed adhesive properties of fibrin and demonstrated the dependence of
      adhesive properties and applied settings. Furthermore the method was suitable to
      screen for potential adhesives and to identify a promising candidate for
      cartilage and bone applications. The method can offer simple, replicable and
      efficient evaluation of adhesive properties in ex vivo specimens and may be a
      useful supplement to existing methods in clinical relevant settings.

PMID- 22984927
TI  - Atomic-scale confinement of resonant optical fields.
AB  - In the presence of matter, there is no fundamental limit preventing confinement
      of visible light even down to atomic scales. Achieving such confinement and the
      corresponding resonant intensity enhancement inevitably requires simultaneous
      control over atomic-scale details of material structures and over the optical
      modes that such structures support. By means of self-assembly we have obtained
      side-by-side aligned gold nanorod dimers with robust atomically defined gaps
      reaching below 0.5 nm. The existence of atomically confined light fields in these
      gaps is demonstrated by observing extreme Coulomb splitting of corresponding
      symmetric and antisymmetric dimer eigenmodes of more than 800 meV in white-light
      scattering experiments. Our results open new perspectives for atomically resolved
      spectroscopic imaging, deeply nonlinear optics, ultrasensing, cavity
      optomechanics, as well as for the realization of novel quantum-optical devices.

PMID- 22984928
TI  - Identification of peptides from foot-and-mouth disease virus structural proteins
      bound by class I swine leukocyte antigen (SLA) alleles, SLA-1*0401 and SLA
      2*0401.
AB  - Characterization of the peptide-binding specificity of swine leukocyte antigen
      (SLA) class I and II molecules is critical to the understanding of adaptive
      immune responses of swine toward infectious pathogens. Here, we describe the
      complete binding motif of the SLA-2*0401 molecule based on a positional scanning
      combinatorial peptide library approach. By combining this binding motif with data
      achieved by applying the NetMHCpan peptide prediction algorithm to both SLA
      1*0401 and SLA-2*0401, we identified high-affinity binding peptides. A total of
      727 different 9mer and 726 different 10mer peptides within the structural
      proteins of foot-and-mouth disease virus (FMDV), strain A24 were analyzed as
      candidate T-cell epitopes. Peptides predicted by the NetMHCpan were tested in
      ELISA for binding to the SLA-1*0401 and SLA-2*0401 major histocompatibility
      complex class I proteins. Four of the 10 predicted FMDV peptides bound to SLA
      2*0401, whereas five of the nine predicted FMDV peptides bound to SLA-1*0401.
      These methods provide the characterization of T-cell epitopes in response to
      pathogens in more detail. The development of such approaches to analyze vaccine
      performance will contribute to a more accelerated improvement of livestock
      vaccines by virtue of identifying and focusing analysis on bona fide T-cell
      epitopes.

PMID- 22984929
TI  - Acute lung injury results from failure of neutrophil de-priming: a new
      hypothesis.
AB  - Neutrophils are the most abundant circulating white cell in humans and play a
      crucial role in the innate immune response. Accumulation and activation of
      neutrophils, together with delayed clearance, have been shown to be a key event
      in the pathogenesis of acute lung injury. Previously, it has been proposed that
      there is substantial pooling of neutrophils within the pulmonary vasculature,
      even under physiological conditions, making the lung especially vulnerable to
      neutrophil-mediated tissue injury. However, more recent evidence suggests that
      only primed neutrophils accumulate in the pulmonary vasculature. This article
      examines the evidence for these two opposing views and proposes a new two-step
      model for the recruitment of neutrophils into the lung. Firstly, neutrophils that
      become primed, by exposure to a range of inflammatory mediators or
      physicochemical perturbations, become shape changed and stiff because of
      alterations in their cytoskeleton, and as a result, accumulate within the
      pulmonary circulation. In the absence of further stimuli, the healthy pulmonary
      vasculature is able to selectively retained these primed cells, allow them to 'de
      prime' and be released back into the circulation in a quiescent, state. If this
      pulmonary 'de-priming' mechanism fails, or a second insult occurs, such as
      ventilator-associated barotrauma, which causes loss of alveolar integrity, primed
      neutrophils migrate from the pulmonary vasculature into the interstitial space
      with resultant lung injury. This canonical 'two step' model highlights the
      importance of neutrophil priming in the genesis of lung injury and the importance
      of adopting strategies to minimise alveolar injury.

PMID- 22984930
TI  - Biobased polymers: synthesis of graft copolymers and comb polymers using lactic
      acid macromonomer and properties of the product polymers.
AB  - For developing broader application of biobased polymers, graft copolymers and
      comb polymers having poly(lactic acid) (PLA) side chains have been synthesized by
      using a macromonomer technique. PLA macromonomers (MMm) having a methacryloyl
      polymerizable group with different PLA chain length with an average length m = 4,
      6, 8, 12, 18, and 30 were prepared via ring-opening polymerization of l-lactide
      using hydroxyethyl methacrylate (HEMA) initiator catalyzed by Sn(Oct)(2). Radical
      polymerization behaviors of these macromonomers were examined. Radical
      copolymerization of MMm (m = 4, 6, and 8), with vinyl monomers like n-butyl
      methacrylate (BMA) and n-butyl acrylate (BA) in water as the reaction medium,
      gave stable miniemulsions of poly[n-butyl (meth)acrylate-graft-lactic acid]s
      [PB(M)A-g-PLAm]. MMm with m value higher than 12, however, gave aggregate
      products in a minor amount besides miniemulsions in a major amount, producing not
      a stable emulsion system of graft copolymers. The solution copolymerization, on
      the other hand, produced a wider variety of the graft copolymers, where a wider
      range of MMm (even m >= 12) can be employed. In a 1,4-dioxane solution, the
      radical copolymerization of MMm with BMA and methyl methacrylate (MMA) gave
      various graft copolymers [PB(M)MA-g-PLAm]. A new type of comb polymers (PMMm)
      having PLAm as pendant side chains were obtained by radical homopolymerization of
      MMm in a 1,4-dioxane solution. The graft copolymers and comb polymers obtained
      here are amorphous. Physical properties of the polymers from miniemulsions
      suggested them to be applicable for coatings or elastic materials which are
      environmentally desirable as a new class of biobased polymers. In addition, the
      present approach provided fundamental information on relationships between the
      length of PLA side chain and the bulk properties of the product polymers.

PMID- 22984931
TI  - Primary liver leiomyoma: a review of this unusual tumour.
AB  - Primary liver leiomyoma (PLL) should be considered in the differential diagnosis
      of liver lesions. A literature review has been completed and two cases are
      reported. The first is a 45-year-old white woman complaining of vague abdominal
      pain. She was initially evaluated with abdominal ultrasonography (US) that
      revealed a heterogeneous liver mass measuring 18 cm in greatest diameter. The
      tumour demonstrated hypointensity on T1-weighted and hyperintensity on T2
      weighted magnetic resonance imaging. The second case is a 45-year-old Asian male
      who had undergone kidney transplantation 16 years ago for IgA glomerulonephritis
      and who developed mild, self-limiting epigastric pain. US showed a 4.3-cm
      diameter lesion that was predominantly hypoechoic and was either compressing or
      arising from segment 2 of the liver. Computed tomography showed a well
      circumscribed 4-cm-diameter mass that appeared to be arising from segments 2/3 of
      the liver and was adjacent to the anterior gastric wall. He underwent an
      uneventful laparoscopic left lateral sectionectomy and discharged on post
      operative day 3. Pathological examination of the resection specimen confirmed the
      lesion as a PLL in each case. Herein, we report two cases of PLL and review the
      literature regarding this uncommon disorder.

PMID- 22984932
TI  - Rate coefficients and reaction mechanism for the reaction of OH radicals with (E)
      CF3CH?CHF, (Z)-CF3CH?CHF, (E)-CF3CF?CHF, and (Z)-CF3CF?CHF between 200 and 400 K:
      hybrid density functional theory and canonical variational transition state
      theory calculations.
AB  - The rate coefficients of ((E)-CF(3)CH?CHF, (Z)-CF(3)CH?CHF, (E)-CF(3)CF?CHF, and
      (Z)-CF(3)CF?CHF) + OH reactions were computed using M06-2X/6-31+G(d,p) theory in
      the temperature range of 200 and 400 K. The possible reaction mechanisms of the
      ((E)-CF(3)CH?CHF, (Z)-CF(3)CH?CHF, (E)-CF(3)CF?CHF, and (Z)-CF(3)CF?CHF) + OH
      reactions were examined. The rate coefficients for the addition and abstraction
      reactions were calculated using canonical variational transition state theory
      (CVT) and conventional transition state theory (CTST), respectively, and we
      concluded that abstraction reactions are negligible within the temperature range
      and addition reactions take the lead role. The small curvature tunnelling (SCT)
      was included in the computation of the rate coefficients. The temperature
      dependent rate expressions (in cm(3) molecule(-1) s(-1)) of the (E)-CF(3)CH?CHF,
      (Z)-CF(3)CH?CHF, (E)-CF(3)CF?CHF, and (Z)-CF(3)CF?CHF + OH reactions between 200
      and 400 K are presented. The atmospheric lifetimes and global warming potentials
      (GWPs) of the test molecules were computed using the rate coefficients obtained
      in this study, and it is concluded that these molecules are very short-lived in
      the Earth's atmosphere with low GWPs.

PMID- 22984934
TI  - An update on antidepressant use and suicidality in pediatric depression.
AB  - INTRODUCTION: In 2003, public health advisories in North America and Europe
      regarding suicidality associated with selective serotonin reuptake inhibitors
      (SSRIs) led to the addition of black box warnings to antidepressant package
      inserts in 2004. Subsequently, a series of events appeared to result from these
      regulatory actions. AREAS COVERED: This review provides an overview of the
      temporal associations of regulatory agencies' actions in North America and Europe
      with rates of depression diagnoses, pediatric antidepressant prescription rates,
      follow-up visits to physicians prescribing antidepressants, and rates of
      completed suicide and suicidal ideation in children and adolescents. In addition,
      evidence-based predictors of suicidal behavior and suicide risk, as provided by
      large, multisite studies of depressed children and adolescents, are outlined.
      Finally, this review considers key advancements in the study of young patients at
      risk for suicide and describes innovations in current research methodology, to
      more accurately identify suicidality and the relationship to antidepressant use
      within this vulnerable patient population. EXPERT OPINION: Evaluating the role of
      antidepressants in those youths who do not respond to evidence-based
      psychotherapeutic interventions may be a useful future research direction. Until
      more data are available, however, closely monitored antidepressant treatment in
      combination with CBT may provide the most benefit.

PMID- 22984935
TI  - An update on the pharmacological management of female sexual dysfunction.
AB  - INTRODUCTION: Female sexual dysfunction (FSD) is a global health issue, with as
      many as 12% of women over 18 years old reporting sexual difficulties associated
      with distress. It is a multifaceted problem with psychological and biological
      causes. Affected women tend to have an impaired quality of life, a decreased
      level of well-being and relationship issues. Hence there is a need for management
      options for affected women. AREAS COVERED: This paper focuses on current
      pharmacological options for the treatment of FSD, particularly estrogens and
      androgens, which have been extensively studied. Some investigational drugs are
      also described, including the centrally acting agents such as flibanserin and
      bupropion, and intravaginal DHEA and testosterone, which may be useful as an
      alternative for women with specific conditions, such as breast cancer survivors.
      EXPERT OPINION: Although approval for the use of testosterone for treatment of
      FSD is limited to some European countries and restricted to surgically menopausal
      women, there is extensive off-label use for this purpose. No other product has
      yet achieved regulatory approval for treatment of FSD. Completion of studies of
      nonhormonal FSD therapies and safety studies of testosterone may result in
      regulatory approval of such products for the treatment of FSD in the near future.

PMID- 22984936
TI  - Current status and future perspectives in the endocrine treatment of
      postmenopausal, hormone receptor-positive metastatic breast cancer.
AB  - INTRODUCTION: Endocrine therapy is a fundamental component of the therapeutic
      repertoire for treatment of metastatic, hormone receptor-positive breast cancer.
      Inevitably, however, tumors develop resistance to these compounds, and overcoming
      this phenomenon is a key motivator of research in this field. AREAS COVERED: This
      review summarizes the current status of endocrine therapy for the treatment of
      metastatic disease, with a main focus on postmenopausal patients. Furthermore,
      strategies that could potentially sustain endocrine resistance and future
      perspectives in this direction are also to be described. Relevant references were
      identified by PubMed searches and from the abstract books of the annual meetings
      of The European Society of Clinical Oncology (ESMO), The American Society of
      Clinical Oncology (ASCO) and from the San Antonio Breast Cancer Symposia. EXPERT
      OPINION: Combinations of endocrine therapy with HER2 targeting agents, as well as
      with compounds that can interfere with PI3K/Akt/mTOR signaling, are two promising
      strategies for delaying or overcoming endocrine resistance, mediated by these
      relevant biological pathways. Due to increased costs and the burden of toxicity
      associated with these combination therapies, compared to endocrine therapy alone,
      it is imperative to concentrate efforts on establishing biomarkers that can
      predict efficacy.

PMID- 22984937
TI  - Dysmenorrhea in adolescents and young adults: an update on pharmacological
      treatments and management strategies.
AB  - INTRODUCTION: Dysmenorrhea is the most common gynecologic complaint among
      adolescents/young adults. Dysmenorrhea is usually primary and is associated with
      normal ovulatory cycles and with no pelvic pathology. Potent prostaglandins and
      potent leukotrienes play an important role in generating primary dysmenorrhea
      symptoms. Adolescents/young adults with severe dysmenorrhea symptoms may have
      pelvic abnormalities, such as endometriosis or uterine anomalies (secondary
      dysmenorrhea). AREAS COVERED: This review provides an update on treatments and
      management strategies of dysmenorrhea in adolescents/young adults. Medical
      literature articles were retrieved using a Medline search on primary and
      secondary dysmenorrhea. Original articles from peer-reviewed journals were
      selected based on relevance. EXPERT OPINION: Treatment with nonsteroidal anti
      inflammatory drugs (NSAIDs) is the preferred initial treatment for dysmenorrhea
      in nonsexually active adolescents/young adults. Adolescents/young adults with
      symptoms that do not respond to NSAIDs for three menstrual periods should be
      offered hormonal treatment, such as combined estrogen and progestin oral
      contraceptive pills (OCPs), for three menstrual cycles. If dysmenorrhea does not
      improve within 6 months of NSAIDs and OCPs, a laparoscopy is indicated to look
      for endometriosis, which is the most common reason for secondary dysmenorrhea.

PMID- 22984938
TI  - Treatment of bacterial meningitis: an update.
AB  - INTRODUCTION: The introduction of protein conjugate vaccines for Haemophilus
      influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria
      meningitidis (N. menigitidis) has changed the epidemiology of bacterial
      meningitis. Bacterial meningitis continues to be an important cause of mortality
      and morbidity, and our incomplete knowledge of its pathogenesis and emergence of
      antimicrobial resistant bacteria contribute to such mortality and morbidity. An
      early empiric antibiotic treatment is critical for the management of patients
      with bacterial meningitis. AREAS COVERED: This article gives an overview on
      optimal treatment strategies of bacterial meningitis, along with considerations
      of new insights on epidemiology, clinical and laboratory findings supportive of
      bacterial meningitis, chemoprophylaxis, selection of initial antimicrobial agents
      for suspected bacterial meningitis, antimicrobial resistance and utility of new
      antibiotics, status on anti-inflammatory agents and adjunctive therapy, and
      pathogenesis of bacterial meningitis. EXPERT OPINION: Prompt treatment of
      bacterial meningitis with an appropriate antibiotic is essential. Optimal
      antimicrobial treatment of bacterial meningitis requires bactericidal agents able
      to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid
      (CSF). Several new antibiotics have been introduced for the treatment of
      meningitis caused by resistant bacteria, but their use in human studies has been
      limited. More complete understanding of the microbial and host interactions that
      are involved in the pathogenesis of bacterial meningitis and associated
      neurologic sequelae is likely to help in developing new strategies for the
      prevention and therapy of bacterial meningitis.

PMID- 22984939
TI  - Anogenital distance and the risk of prostate cancer.

PMID- 22984940
TI  - Predicting and avoiding subcellular compartmentalization artifacts arising from
      acetoxymethyl ester calcium imaging probes. The case of fluo-3 AM and a general
      account of the phenomenon including a problem avoidance chart.
AB  - Stimulated by difficulties experienced when using fluo-3 AM, we developed a
      general mechanistic model to aid understanding and practical application of
      calcium probes applied as acetoxymethyl (AM) esters. Several practical issues
      previously overlooked or under-emphasized are considered by this model. First,
      some AM ester probes are "super" lipophilic, e.g., calcium orange, fluo-3, fura
      red, and these are trapped in the plasma membrane. Entry of such compounds into
      cells requires the presence of serum albumin in the incubation medium or esterase
      in the plasma membrane or both. Second, visible cytosolic calcium signals require
      significant cytosolic esterase, which varies considerably among cell lines and
      within cell populations of a single cell line. Finally, compartmentalization
      artefacts are most likely when incompletely hydrolyzed esters are present in the
      cytosol. This can occur because of low cytosolic esterase concentration or
      activity, and especially when long incubation times or high extracellular probe
      concentrations are used. An additional factor favoring compartmentalization is
      the presence of the "salt" form of the probe in the cytosol in the absence of
      significant concentrations of calcium ions. We provide an algorithmic chart to
      aid assessment of possible compartmentalization, guides to relevant QSAR models,
      and notes on estimation of the structural parameters required when using these
      models.

PMID- 22984941
TI  - External heavy-atomic construction of photosensitizer nanoparticles for enhanced
      in vitro photodynamic therapy of cancer.
AB  - Introduction of heavy atoms around photosensitizers (PSs) generally facilitates
      intersystem crossing (ISC) and improves their quantum yield of singlet oxygen
      ((1)O(2)) generation ability, which is a key species in photodynamic therapy
      (PDT). Here, we report Pt(IV)- and Au(III)-modified silica nanoparticles (SN) as
      the drug delivery system of a hypocrellin A (HA) to improve its photodynamic
      activity through external heavy atom effect. Comparative studies with Pt- and Au
      modified and unmodified nanoparticles have demonstrated that the intraparticle
      external heavy atom effect on the encapsulated HA molecules significantly
      enhances their efficiency of (1)O(2) generation and, thereby, the in vitro
      photodynamic efficacy to cancer cells. The results well elucidated the potential
      of our PSs/heavy metal ions doped nanocarrier for improving the actual efficacy
      of PDT.

PMID- 22984942
TI  - First report of New Delhi metallo-beta-lactamase-1-producing Klebsiella
      pneumoniae in Iran.
AB  - New Delhi metallo-beta-lactamase (NDM-1) is a novel metallo-beta-lactamase (MBL).
      Sporadic cases of NDM-1 positive strains have been reported from different
      countries, suggesting a widespread dissemination. The aim of this study was the
      detection of MBLs in Enterobacteriaceae isolated from patients in Tehran
      hospitals. After identification tests, the susceptibility to the antibiotics was
      done by Kirby-Bauer method and broth microdilution. Carbapenem-resistant isolates
      were tested for carbapenemase production using the modified Hodge test (MHT).
      Carbapenem-resistant strains screened for bla(KPC) gene and genes encoding MBLs.
      Twenty-three isolates (6.3%) were resistant to meropenem, eleven isolates (3%)
      were resistant to ertapenem, and four isolates (1.1%) were resistant to imipenem.
      MHT was positive in 11 (47.8%) of the carbapenem-resistant isolates. In March
      2011, we detected a multiple drug-resistant Klebsiella pneumoniae isolate that
      was resistant to all tested antibiotics except colistin. PCR confirmed that this
      isolate contained bla(NDM-1), bla(TEM), bla(SHV), and bla(CTX-M). This is the
      first report on the detection of MBL NDM-1 in Iran. The rapid spread of NDM-1
      positive bacteria proved to be a major challenge for the treatment and control of
      infectious diseases.

PMID- 22984943
TI  - Global protein expression profile response of Escherichia coli ATCC 25922 exposed
      to enrofloxacin.
AB  - Although enrofloxacin (ENR) is widely used for therapy of bacterial infections in
      the veterinary clinical, bacterial resistance to ENR is becoming an increasing
      worldwide problem. The primary global response of Escherichia coli to ENR
      exposure before resistance is largely unknown on the proteomic level. The purpose
      of this study was to understand the physiological response of E. coli to a
      subinhibitory concentration of ENR using proteomic methods. Differentially
      expressed proteins of the whole-cell extracts were visualized by two-dimensional
      gel electrophoresis, and the selected proteins were purified and identified by
      MALDI-TOF/mass spectrometry analysis. The result showed that the number of
      proteins (mean+/-standard deviation) detected in the ENR-treated strains was
      significantly (p<0.05) reduced from 1115+/-25 to 732+/-19. In total, 42
      differentially expressed proteins with more than twofold difference were
      identified, including 13 upregulated proteins (p<0.05) and 17 downregulated
      proteins (p<0.05), as well as the specific proteins expressed in the group with
      or without ENR-treated cells. The results show that the differentially expressed
      proteins identified in E. coli exposed to ENR included proteins involved with a
      classic resistance mechanism, such as bacterial cell membrane permeability
      mediated by OmpX and OmpW, and other adaptive changes that appear to represent
      the physiological basis and background of resistance to ENR.

PMID- 22984944
TI  - A case of canine poisoning with New Zealand Tree Nettle (Ongaonga, Urtica ferox).

PMID- 22984945
TI  - Differential investment in pre- vs. post-copulatory sexual selection reinforces a
      cross-continental reversal of sexual size dimorphism in Sepsis punctum (Diptera:
      Sepsidae).
AB  - Theory predicts that males have a limited amount of resources to invest in
      reproduction, suggesting a trade-off between traits that enhance mate acquisition
      and those that enhance fertilization success. Here, we investigate the
      relationship between pre- and post-copulatory investment by comparing the mating
      behaviour and reproductive morphology of four European and five North American
      populations of the dung fly Sepsis punctum (Diptera) that display a reversal of
      sexual size dimorphism (SSD). We show that the geographic reversal in SSD between
      the continents (male biased in Europe, female biased in North America) is
      accompanied by differential investment in pre- vs. post-copulatory traits. We
      find higher remating rates in European populations, where larger males acquire
      more matings and consequently have evolved relatively larger testes and steeper
      hyper-allometry with body size. American populations, in sharp contrast, display
      much reduced, if any, effect of body size on those traits. Instead, North
      American males demonstrate an increased investment in mate acquisition prior to
      copulation, with more mounting attempts and a distinctive abdominal courtship
      display that is completely absent in Europe. When controlling for body size,
      relative female spermathecal size is similar on both continents, so we find no
      direct evidence for the co-evolution of male and female internal reproductive
      morphology. By comparing allopatric populations of the same species that
      apparently have evolved different mating systems and consequently SSD, we thus
      indirectly demonstrate differential investment in pre- vs. post-copulatory
      mechanisms increasing reproductive success.

PMID- 22984946
TI  - A common clathrin-mediated machinery co-ordinates cell-cell adhesion and
      bacterial internalization.
AB  - Invasive bacterial pathogens often target cellular proteins involved in adhesion
      as a first event during infection. For example, Listeria monocytogenes uses the
      bacterial protein InlA to interact with E-cadherin, hijack the host adherens
      junction (AJ) machinery and invade non-phagocytic cells by a clathrin-dependent
      mechanism. Here, we investigate a potential role for clathrin in cell-cell
      adhesion. We observed that the initial steps of AJ formation trigger the
      phosphorylation of clathrin, and its transient localization at forming cell-cell
      contacts. Furthermore, we show that clathrin serves as a hub for the recruitment
      of proteins that are necessary for the actin rearrangements that accompany the
      maturation of AJs. Using an InlA/E-cadherin chimera, we show that adherent cells
      expressing the chimera form AJs with cells expressing E-cadherin. We demonstrate
      that non-adherent cells expressing the InlA chimera, as bacteria, can be
      internalized by E-cadherin-expressing adherent cells. Together these results
      reveal that a common clathrin-mediated machinery may regulate internalization and
      cell adhesion and that the relative mobility of one of the interacting partners
      plays an important role in the commitment to either one of these processes.

PMID- 22984947
TI  - Correlation analysis of the side-chains conformational distribution in bound and
      unbound proteins.
AB  - BACKGROUND: Protein interactions play a key role in life processes.
      Characterization of conformational properties of protein-protein interactions is
      important for understanding the mechanisms of protein association. The rapidly
      increasing amount of experimentally determined structures of proteins and protein
      protein complexes provides foundation for research on protein interactions and
      complex formation. The knowledge of the conformations of the surface side chains
      is essential for modeling of protein complexes. The purpose of this study was to
      analyze and compare dihedral angle distribution functions of the side chains at
      the interface and non-interface areas in bound and unbound proteins. RESULTS: To
      calculate the dihedral angle distribution functions, the configuration space was
      divided into grid cells. Statistical analysis showed that the similarity between
      bound and unbound interface and non-interface surface depends on the amino acid
      type and the grid resolution. The correlation coefficients between the
      distribution functions increased with the grid spacing increase for all amino
      acid types. The Manhattan distance showing the degree of dissimilarity between
      the distribution functions decreased accordingly. Short residues with one or two
      dihedral angles had higher correlations and smaller Manhattan distances than the
      longer residues. Met and Arg had the slowest growth of the correlation
      coefficient with the grid spacing increase. The correlations between the
      interface and non-interface distribution functions had a similar dependence on
      the grid resolution in both bound and unbound states. The interface and non
      interface differences between bound and unbound distribution functions, caused by
      biological protein-protein interactions or crystal contacts, disappeared at the
      70 degrees  grid spacing for interfaces and 30 degrees  for non-interface
      surface, which agrees with an average span of the side-chain rotamers.
      CONCLUSIONS: The two-fold difference in the critical grid spacing indicates
      larger conformational changes upon binding at the interface than at the rest of
      the surface. At the same time, transitions between rotamers induced by
      interactions across the interface or the crystal packing are rare, with most side
      chains having local readjustments that do not change the rotameric state. The
      analysis is important for better understanding of protein interactions and
      development of flexible docking approaches.

PMID- 22984948
TI  - Optimization of a small tropomyosin-related kinase B (TrkB) agonist 7,8
      dihydroxyflavone active in mouse models of depression.
AB  - Structure-activity relationship study shows that the catechol group in 7,8
      dihdyroxyflavone, a selective small TrkB receptor agonist, is critical for
      agonistic activity. To improve the poor pharmacokinetic profiles intrinsic to
      catechol-containing molecules and to elevate the agonistic effect of the lead
      compound, we initiated the lead optimization campaign by synthesizing various
      bioisosteric derivatives. Here we show that the optimized 2-methyl-8-(4'
      (pyrrolidin-1-yl)phenyl)chromeno[7,8-d]imidazol-6(1H)-one derivative possesses
      enhanced TrkB stimulatory activity. Chronic oral administration of this compound
      significantly reduces the immobility in forced swim test and tail suspension
      test, two classical antidepressant behavioral animal models, which is accompanied
      by robust TrkB activation in hippocampus of mouse brain. Further, in vitro ADMET
      studies demonstrate that this compound possesses the improved features compared
      to the previous lead compound. Hence, this optimized compound may act as a
      promising lead candidate for in-depth drug development for treating various
      neurological disorders including depression.

PMID- 22984949
TI  - A matter of matching: how goals and primes affect self-agency experiences.
AB  - The sense of self-agency is a pervasive experience that people infer from their
      actions and the outcomes they produce. Recent research suggests that self-agency
      inferences arise from an explicit goal-directed process as well as an implicit
      outcome-priming process. Three experiments examined potential differences between
      these 2 processes. Participants had the goal to produce an outcome or were primed
      with the outcome. Next, they performed an action in an agency-ambiguous
      situation, followed by an outcome that matched or mismatched the goal or prime,
      and indicated experienced self-agency over the action-outcome. Results showed
      that goals reduce self-agency over mismatching outcomes. However, outcome-primes
      did not affect self-agency over mismatching outcomes but even enhanced self
      agency over mismatching proximate outcomes. Goals and outcome-primes equally
      enhanced self-agency for matches. Our findings provide novel evidence that self
      agency experiences result from 2 distinct inferential routes and that goals and
      primes differentially affect the perception of our own behavior.

PMID- 22984950
TI  - A role for memory in prospective timing informs timing in prospective memory.
AB  - Time-based prospective memory (TBPM) tasks require the estimation of time in
      passing-known as prospective timing. Prospective timing is said to depend on an
      attentionally driven internal clock mechanism and is thought to be unaffected by
      memory for interval information (for reviews see, Block, Hancock, & Zakay, 2010;
      Block & Zakay, 1997). A prospective timing task that required a verbal estimate
      following the entire interval (Experiment 1) and a TBPM task that required
      production of a target response during the interval (Experiment 2) were used to
      test an alternative view that episodic memory does influence prospective timing.
      In both experiments, participants performed an ongoing lexical decision task of
      fixed duration while a varying number of songs were played in the background.
      Experiment 1 results revealed that verbal time estimates became longer the more
      songs participants remembered from the interval, suggesting that memory for
      interval information influences prospective time estimates. In Experiment 2,
      participants who were asked to perform the TBPM task without the aid of an
      external clock made their target responses earlier as the number of songs
      increased, indicating that prospective estimates of elapsed time increased as
      more songs were experienced. For participants who had access to a clock, changes
      in clock checking coincided with the occurrence of song boundaries, indicating
      that participants used both song information and clock information to estimate
      time. Finally, ongoing task performance and verbal reports in both experiments
      further substantiate a role for episodic memory in prospective timing.

PMID- 22984952
TI  - Prevention and correction in post-error performance: an ounce of prevention, a
      pound of cure.
AB  - Error detection serves 2 different functions: prevention and cure. Prevention
      engages post-error slowing to reduce future errors, whereas cure engages
      processes that correct the error. Thus, prevention predicts post-error slowing,
      and cure does not. We investigated this distinction in skilled typists in 3
      experiments. In Experiment 1, post-error performance was investigated in 800
      typists who completed a short continuous typing test where correction was
      disallowed. In Experiments 2 and 3, post-error performance and post-correction
      performance were investigated by manipulating whether typists were allowed to
      correct their mistakes. Across experiments, there was limited evidence that
      typists used error detection for prevention; typists preferred the cure. After
      making mistakes, they corrected them and rapidly resumed typing at normal rates.
      Post-error slowing occurred only when correction was disabled; post-error
      speeding occurred when correction was enabled. This finding offers support for
      the novel hypothesis that post-error slowing reflects the inhibition of pre
      potent tendencies to correct mistakes. Error-detection processes in general will
      be better understood by distinguishing between tasks that allow performers to
      cure their errors through correction rather than reduce their errors through
      prevention.

PMID- 22984951
TI  - Getting the gist of events: recognition of two-participant actions from brief
      displays.
AB  - Unlike rapid scene and object recognition from brief displays, little is known
      about recognition of event categories and event roles from minimal visual
      information. In 3 experiments, we displayed naturalistic photographs of a wide
      range of 2-participant event scenes for 37 ms and 73 ms followed by a mask, and
      found that event categories (the event gist; e.g., "kicking," "pushing") and
      event roles (i.e., Agent and Patient) can be recognized rapidly, even with
      various actor pairs and backgrounds. Norming ratings from a subsequent experiment
      revealed that certain physical features (e.g., outstretched extremities) that
      correlate with Agent-hood could have contributed to rapid role recognition. In a
      final experiment, using identical twin actors, we then varied these features in 2
      sets of stimuli, in which Patients had Agent-like features or not. Subjects
      recognized the roles of event participants less accurately when Patients
      possessed Agent-like features, with this difference being eliminated with 2-s
      durations. Thus, given minimal visual input, typical Agent-like physical features
      are used in role recognition, but with sufficient input from multiple fixations,
      people categorically determine the relationship between event participants.

PMID- 22984953
TI  - When forced fabrications become truth: causal explanations and false memory
      development.
AB  - Studies of text comprehension have amply demonstrated that when reading a story,
      people seek to identify the causal and motivational forces that drive the
      interactions of characters and link events (e.g., Zwaan, Langston, & Graesser,
      1995), thereby achieving explanatory coherence. In the present study we provide
      the first evidence that the search for explanatory coherence also plays a role in
      the memory errors that result from suggestive forensic interviews. Using a forced
      fabrication paradigm (e.g., Chrobak & Zaragoza, 2008), we conducted 3 experiments
      to test the hypothesis that false memory development is a function of the
      explanatory role these forced fabrications served (the explanatory role
      hypothesis). In support of this hypothesis, participants were more likely to
      subsequently freely report (Experiment 1) and falsely assent to (Experiment 2)
      their forced fabrications when they helped to provide a causal explanation for a
      witnessed outcome than when they did not serve this explanatory role.
      Participants were also less likely to report their forced fabrications when their
      explanatory strength had been reduced by the presence of an alternative
      explanation that could explain the same outcome as their fabrication (Experiment
      3). These findings extend prior research on narrative and event comprehension
      processes by showing that the search for explanatory coherence can continue for
      weeks after the witnessed event is initially perceived, such that causally
      relevant misinformation from subsequent interviews is, over time, incorporated
      into memory for the earlier witnessed event.

PMID- 22984954
TI  - The costly filtering of potential distraction: evidence for a supramodal
      mechanism.
AB  - When dealing with significant sensory stimuli, performance can be hampered by
      distracting events. Attention mechanisms lessen such negative effects, enabling
      selection of relevant information while blocking potential distraction. Recent
      work shows that preparatory brain activity, occurring before a critical stimulus,
      may reflect mechanisms of attentional control aimed to filter upcoming
      distracters. However, it is unknown whether the engagement of these filtering
      mechanisms to counteract distraction in itself taxes cognitive-brain systems,
      leading to performance costs. Here we address this question and, specifically,
      seek the behavioral signature of a mechanism for the filtering of potential
      distraction within and between sensory modalities. We show that, in potentially
      distracting contexts, a filtering mechanism is engaged to cope with forthcoming
      distraction, causing a dramatic behavioral cost in no-distracter trials during a
      speeded tactile discrimination task. We thus demonstrate an impaired processing
      caused by a potential, yet absent, distracter. This effect generalizes across
      different sensory modalities, such as vision and audition, and across different
      manipulations of the context, such as the distracter's sensory modality and
      pertinence to the task. Moreover, activation of the filtering mechanism relies on
      both strategic and reactive processes, as shown by its dynamic dependence on
      probabilistic and cross-trial contingencies. Crucially, across participants, the
      observed strategic cost is inversely related to the interference exerted by a
      distracter on distracter-present trials. These results attest to a mechanism for
      the monitoring and filtering of potential distraction in the human brain.
      Although its activation is indisputably beneficial when distraction occurs, it
      leads to robust costs when distraction is actually expected but currently absent.

PMID- 22984955
TI  - Methods for insulin delivery and glucose monitoring in diabetes: summary of a
      comparative effectiveness review.
AB  - BACKGROUND: Diabetes mellitus is defined as a group of metabolic diseases
      characterized by hyperglycemia, which when untreated can lead to long-term
      complications, including micro- and macrovascular complications. Tight glycemic
      control with intensive insulin therapy has been suggested to reduce the risk of
      such complications in several diabetes populations; however, such an approach can
      also be associated with risks and challenges. There are currently several
      modalities available to deliver insulin and monitor glucose levels to achieve
      glycemic goals in diabetic patients. In July 2012, the Agency for Healthcare
      Research and Quality (AHRQ) published a systematic review on the comparative
      effectiveness of insulin delivery systems and glucose-monitoring modalities in
      diabetic patients receiving intensive insulin therapy. Studies from 44
      publications included in the review compared the effects of continuous
      subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) and/or
      real time-continuous glucose monitoring (rt-CGM) with self-monitoring of blood
      glucose (SMBG) among children, adolescents, or adults with either type 1 (T1DM)
      or type 2 diabetes (T2DM), or pregnant women with pre-existing diabetes (either
      T1DM or T2DM). This comparative effectiveness review evaluated which modality
      results in improved glycemic control, less hypoglycemia, better quality of life,
      and/or improved clinical outcomes. The numerous technologies and the challenges
      that clinicians face when determining which patient population may benefit from
      different insulin delivery systems and glucose-monitoring approaches motivated
      AHRQ to synthesize the available information to assist health professionals in
      making evidence-based practice decisions for their patients. The review also
      delineates advances in insulin delivery and glucose-monitoring systems, practical
      methods to achieve tight glycemic control and strategies to minimize associated
      risks, as well as highlights gaps in research and areas that need to be addressed
      in the future.  OBJECTIVES: To (a) educate health care professionals on the
      findings from AHRQ's 2012 comparative effectiveness review on insulin delivery
      and glucose-monitoring modalities in patients with diabetes; (b) apply review
      findings to make treatment decisions in clinical practice; and (c) identify
      shortcomings in the current research and future directions relating to the
      comparative effectiveness of insulin delivery and glucose-monitoring modalities
      for patients with diabetes. SUMMARY: The AHRQ systematic review of randomized
      clinical trials reveals that both insulin delivery modalities (CSII and MDI)
      demonstrate similar effectiveness on glycemic control and severe hypoglycemia in
      children and adolescents with T1DM and in adults with T2DM. In adults with T1DM,
      hemoglobin A1c decreased more with CSII than with MDI with low strength of
      evidence, but one study heavily influenced these results. In children and adults
      with T1DM, the use of CSII was associated with improved quality of life compared
      with MDI, with low strength of evidence, while there was insufficient strength of
      evidence to make conclusions regarding the quality of life for adults with T2DM.
      The study investigators suggest that the modality to deliver intensive insulin
      therapy can be individualized to patient preference in order to maximize quality
      of life. On all measured outcomes, there was insufficient or low strength of
      evidence regarding pregnant women with pre-existing diabetes.The AHRQ
      investigators found studies comparing the effectiveness of glucose-monitoring
      modalities in individuals with T1DM only. The systematic review demonstrates that
      rt-CGM is associated with greater lowering of A1c compared with SMBG (high
      strength of evidence) without affecting the risk of severe hypoglycemia (low
      strength of evidence) or quality of life (low strength of evidence) in
      nonpregnant individuals with T1DM, particularly when compliance with device use
      is high. Additional findings suggest that the use of sensor-augmented insulin
      pumps (rt-CGM + CSII) is superior to the use of MDI/SMBG use in lowering A1c in
      nonpregnant individuals with T1DM (moderate strength of evidence). Comparison of
      other outcome measures did not yield firm conclusions due to low or insufficient
      evidence.

PMID- 22984956
TI  - Letter: Mucosal PCR for cytomegalovirus in refractory ulcerative colitis.

PMID- 22984958
TI  - The possible effects of mesalazine on the intestinal microbiota.

PMID- 22984959
TI  - Quantitative global and gene-specific promoter methylation in relation to
      biological properties of neuroblastomas.
AB  - BACKGROUND: In this study we aimed to quantify tumor suppressor gene (TSG)
      promoter methylation densities levels in primary neuroblastoma tumors and cell
      lines. A subset of these TSGs is associated with a CpG island methylator
      phenotype (CIMP) in other tumor types. METHODS: The study panel consisted of 38
      primary tumors, 7 established cell lines and 4 healthy references. Promoter
      methylation was determined by bisulphate Pyrosequencing for 14 TSGs; and LINE-1
      repeat element methylation was used as an indicator of global methylation levels.
      RESULTS: Overall mean TSG Z-scores were significantly increased in cases with
      adverse outcome, but were unrelated to global LINE-1 methylation. CIMP with
      hypermethylation of three or more gene promoters was observed in 6/38 tumors and
      7/7 cell lines. Hypermethylation of one or more TSG (comprising TSGs BLU, CASP8,
      DCR2, CDH1, RASSF1A and RASSF2) was evident in 30/38 tumors. By contrast only
      very low levels of promoter methylation were recorded for APC, DAPK1, NORE1A,
      P14, P16, TP73, PTEN and RARB. Similar involvements of methylation instability
      were revealed between cell line models and neuroblastoma tumors. Separate
      analysis of two proposed CASP8 regulatory regions revealed frequent and
      significant involvement of CpG sites between exon 4 and 5, but modest involvement
      of the exon 1 region. CONCLUSIONS/SIGNIFICANCE: The results highlight the
      involvement of TSG methylation instability in neuroblastoma tumors and cell lines
      using quantitative methods, support the use of DNA methylation analyses as a
      prognostic tool for this tumor type, and underscore the relevance of developing
      demethylating therapies for its treatment.

PMID- 22984960
TI  - SR-BI associates with ABCG1 and inhibits ABCG1-mediated cholesterol efflux from
      cells to high-density lipoprotein 3.
AB  - BACKGROUND: The single and combined effects of scavenger receptor-BI (SR-BI), ATP
      binding cassette transporter (ABC) A1 and G1 on cholesterol efflux from Chinese
      Hamster Ovary (CHO) cells were investigated. RESULTS: When apolipoproteinA-I
      (apoA-I) was used as an acceptor, ABCA1 overexpression led to an increase in
      total cholesterol (TC) in medium which is attributable to a 2-fold increase in
      free cholesterol (FC) content. When high-density lipoprotein 3 (HDL3) was used as
      an acceptor, SR-BI overexpression not only promoted FC efflux, but also promoted
      the uptake of cholesteryl ester (CE) into cells, resulting in no TC varieties in
      medium. Overexpression of ABCG1 increased both the FC and CE levels in medium.
      However, when apoA-I and HDL3 were both used as acceptors, coexpression of SR-BI
      has no effect on ABCA1-mediated increased FC and TC accumulation in medium.
      Interestingly, coexpression of SR-BI with ABCG1 blocked the ABCG1-mediated
      cholesterol efflux to HDL3, mostly by promoting the reuptake of CE from the
      medium. Furthermore, co-immunoprecipitation experiments revealed that SR-BI
      interacted with ABCG1 in BHK cells overexpressing ABCG1 and SR-BI. CONCLUSIONS:
      We found SR-BI associates with ABCG1 and inhibits ABCG1-mediated cholesterol
      efflux from cells to HDL3.

PMID- 22984962
TI  - Clinical and radiological evaluation of a template-guided (NobelGuideTM)
      treatment concept.
AB  - OBJECTIVES: The study was designed to evaluate the clinical use of the
      NobelGuide(TM) concept over a follow-up period of 12 months with respect to
      implant success and survival rates, development of soft tissue condition and
      recording of potential surgical and prosthetic complications. In addition,
      radiological assessment of peri-implant bone levels was performed at the 1-year
      follow-up post-implant placement. MATERIAL AND METHODS: Thirty patients
      (male/female = 15/15) with partially dentate and edentulous mandibles and
      maxillae were included. All patients were planned and operated on using the
      computer-aided, template-guided treatment concept NobelGuide(TM). Overall, 163
      implants (NobelReplace((r)) Tapered Groovy) were placed (mandible/maxilla =
      107/56 implants). Recall appointments were performed after 1-2 weeks, 1, 3, 6 and
      12 months after implant placement. Clinical parameters of the soft tissue
      conditions [e.g. bleeding on probing (BoP), pocket probing depth >=3 mm (PPD),
      marginal plaque index (mPI)] and the dentist's esthetic and functional evaluation
      using a visual analogue scale (VAS) were documented. Marginal bone level was
      evaluated on radiographs made at implant insertion and at the 1-year follow-up.
      RESULTS: All 30 patients with 161 implants completed the 1-year follow-up
      resulting in a cumulative survival rate of 98.8% (two implant losses). Clinical
      parameters improved in a majority of the implants. The mean marginal bone level
      at implant insertion and at 1-year follow-up was reported with 0.17 mm (SD 1.24;
      n = 125) and -1.39 mm (SD 1.27; n = 110), respectively. The mean change in bone
      level from implant insertion to 1 year was -1.44 mm (SD 1.35; n = 98).
      CONCLUSIONS: The 1-year follow-up showed a cumulative survival rate and success
      rate of 98.8% and 96.3%, respectively. Immediate or delayed loading of implants
      using a flapless, guided surgery approach (NobelGuide(TM)) appears to be a viable
      concept demonstrating good clinical and radiographic outcomes at the 1-year time
      point.

PMID- 22984963
TI  - One-piece implants: placement timing, surgical technique, loading protocol, and
      marginal bone loss.
AB  - PURPOSE: Osseointegration being an accepted and well-documented concept,
      attention is now directed towards simplification of the mechanical design of
      implants and towards achieving biomechanical success. The aim of this literature
      review is to provide an overview of the one-piece implant, with its advantages
      and disadvantages over a conventional two-piece implant. METHODS: The PubMed
      database was searched in the English language using the keywords one-piece
      implant, single-piece implant, single-stage implant surgery, and two-piece
      implant. Articles were selected on the basis of whether they had sufficient
      information related to placement timing, surgical procedure used, loading
      protocol, follow-up periods, marginal bone loss, and implant success rates of one
      piece implants. For inclusion, a study group must have had a minimum of 30 one
      piece implants followed for at least 1 year. DISCUSSION: Nineteen articles were
      subjected to the selection criteria. Out of 19 clinical trials only 11 met the
      selection criteria. Five parameters were taken into consideration for studying
      one-piece implants: placement timing, surgical technique, loading protocol,
      marginal bone loss, and implant survival rate. The data from the identified
      studies were tabulated according to these parameters and discussed. CONCLUSION:
      Delayed placement of one-piece implants is more commonly practiced than
      extraction and immediate placement. Most surgeons prefer surgeries using flaps as
      compared to flapless surgeries, and in most cases, one-piece implants were loaded
      immediately. Limited literature reveals both positive and negative results
      regarding the effect of a one-piece implant system on surrounding hard and soft
      tissues.

PMID- 22984961
TI  - Temporal changes in species interactions in simple aquatic bacterial communities.
AB  - BACKGROUND: Organisms modify their environment and in doing so change the
      quantity and possibly the quality of available resources. Due to the two-way
      relationship between organisms and their resource environment, and the complexity
      it brings to biological communities, measuring species interactions reliably in
      any biological system is a challenging task. As the resource environment changes,
      the intensity and even the sign of interactions may vary in time. We used
      Serratia marcescens and Novosphingobium capsulatum bacteria to study how the
      interaction between resource environment and organisms influence the growth of
      the bacterial species during circa 200 generations. We used a sterile-filtering
      method to measure how changes in resource environment are reflected in growth
      rates of the two species. RESULTS: Changes in the resource environment caused
      complex time and species composition-dependent effects on bacterial growth
      performance. Variation in the quality of the growth medium indicated existence of
      temporally fluctuating within-species facilitation and inhibition, and between
      species asymmetric facilitation. CONCLUSIONS: The interactions between the
      community members could not be fully predicted based only on the knowledge of the
      growth performance of each member in isolation. Growth dynamics in sterile
      filtered samples of the conditioned growth medium can reveal both biologically
      meaningful changes in resource availability and temporally changing facilitative
      resource-mediated interactions between study species. This is the first study we
      are aware of where the filter-sterilization - growth assay method is applied to
      study the effect of long-term changes in the environment on species interactions.

PMID- 22984964
TI  - Kinetic stability of the streptavidin-biotin interaction enhanced in the gas
      phase.
AB  - Results of the first detailed study of the structure and kinetic stability of the
      model high-affinity protein-ligand interaction between biotin (B) and the
      homotetrameric protein complex streptavidin (S(4)) in the gas phase are
      described. Collision cross sections (Omega) measured for protonated gaseous ions
      of free and ligand-bound truncated (residues 13-139) wild-type (WT) streptavidin,
      i.e., S(4)(n+) and (S(4)+4B)(n+) at charge states n = 12-16, were found to be
      independent of charge state and in agreement (within 10%) with values estimated
      for crystal structures reported for S(4) and (S(4)+4B). These results suggest
      that significant structural changes do not occur upon transfer of the complexes
      from solution to the gas phase by electrospray ionization. Temperature-dependent
      rate constants were measured for the loss of B from the protonated (S(4)+4B)(n+)
      ions. Over the temperature range investigated, the kinetic stability increases
      with decreasing charge state, from n = 16 to 13, but is indistinguishable for n =
      12 and 13. A comparison of the activation energies (E(a)) measured for the loss
      of B from the (S(4)+4B)(13+) ions composed of WT streptavidin and five binding
      site mutants (Trp79Phe, Trp108Phe, Trp120Phe, Ser27Ala, and Tyr43Ala) suggests
      that at least some of the specific intermolecular interactions are preserved in
      the gas phase. The results of molecular dynamics simulations performed on WT
      (S(4)+4B)(12+) ions with different charge configurations support this conclusion.
      The most significant finding of this study is that the gaseous WT (S(4)+4B)(n+)
      ions at n = 12-14, owing to a much larger E(a) (by as much as 13 kcal mol(-1))
      for the loss of B, are dramatically more stable kinetically at 25  degrees C than
      the (S(4)+4B) complex in aqueous neutral solution. The differences in E(a) values
      measured for the gaseous (S(4)+4B)(n+) ions and solvated (S(4)+4B) complex can be
      largely accounted for by a late dissociative transition state and the rehydration
      of B and the protein binding cavity in solution.

PMID- 22984966
TI  - Anisotropic volume expansion of crystalline silicon during electrochemical
      lithium insertion: an atomic level rationale.
AB  - The volume expansion of silicon is the most important feature for electrochemical
      operations of high capacity Si anodes in lithium ion batteries. Recently, the
      unexpected anisotropic volume expansion of Si during lithiation has been
      experimentally observed, but its atomic-level origin is still unclear. By
      employing first-principles molecular dynamics simulations, herein, we report that
      the interfacial energy at the phase boundary of amorphous Li(x)Si/crystalline Si
      plays a very critical role in lithium diffusion and thus volume expansion. While
      the interface formation turns out to be favorable at x = 3.4 for all of the
      (100), (110), and (111) orientations, the interfacial energy for the (110)
      interface is the smallest, which is indeed linked to the preferential volume
      expansion along the <110> direction because the preferred (110) interface would
      promote lithiation behind the interface. Utilizing the structural characteristic
      of the Si(110) surface, local Li density at the (110) interface is especially
      high reaching Li(5.5)Si. Our atomic-level calculations enlighten the importance
      of the interfacial energy in the volume expansion of Si and offer an explanation
      for the previously unsolved perspective.

PMID- 22984967
TI  - Oncologic clearance with preservation of reconstructive options: literature
      review and the 'delayed reconstruction after pathology evaluation (DRAPE)'
      technique.
AB  - Intraoperative frozen section and Mohs' micrographic surgery (MMS) are two
      techniques used to ensure oncological clearance without resorting to
      unnecessarily wide margins that might compromise reconstructive options for
      definitive wound closure. In addition to some technical issues, these techniques
      are suboptimal for resection of tumours such as melanoma, where specific tissue
      margins at histopathology are required to ensure minimal risk of local
      recurrence. We describe a technique that minimizes the amount of tissue excised
      and uses definitive paraffin sections interpreted in a pathology laboratory in
      order to delay reconstruction until after clear oncologic margins are obtained.
      This 'delayed reconstruction after pathology evaluation (DRAPE)' technique is
      particularly directed at extensive and complicated skin lesions, located in areas
      of the body that can be difficult to reconstruct and are prone to disfigurement
      and/or loss of function. A review of the literature is undertaken, establishing
      the role of each technique in achieving clear surgical margins. A case example is
      presented, highlighting the role of the DRAPE approach. The DRAPE technique is
      presented as a useful option for high-risk lesions, especially within
      aesthetically sensitive regions or for complex reconstructions, and when
      reconstruction can be reasonably delayed while tumour clearance is established.

PMID- 22984968
TI  - Utility of the P19 suppressor of gene-silencing protein for production of
      therapeutic antibodies in Nicotiana expression hosts.
AB  - To study how the P19 suppressor of gene-silencing protein can be used effectively
      for the production of therapeutic glycoproteins, the following factors were
      examined: the genetic elements used for expressing recombinant proteins; the
      effect of different P19 concentrations; compatibility of P19 with various
      Nicotiana tabacum cultivars for transgenic expression; the glycan profile of a
      recombinant therapeutic glycoprotein co-expressed with P19 in an RNAi-based
      glycomodified Nicotiana benthamiana expression host. The coding sequences for the
      heavy and light chains of trastuzumab were cloned into five plant expression
      vectors (102-106) containing different 5' and 3' UTRs, designated as vector sets
      102-106 mAb. The P19 protein of Tomato bushy stunt virus (TBSV) was also cloned
      into vector 103, which contained the Cauliflower mosaic virus (CaMV) 35S promoter
      and 5'UTR together with the terminator region of the nopaline synthase gene of
      Agrobacterium. Transient expression of the antibody vectors resulted in different
      levels of trastuzumab accumulation, the highest being 105 and 106 mAb at about 1%
      of TSP. P19 increased the concentration of trastuzumab approximately 15-fold (to
      about 2.3% of TSP) when co-expressed with 103 mAb but did not affect antibody
      levels with vectors 102 and 106 mAb. When 103 mAb was expressed together with P19
      in different N. tabacum cultivars, all except Little Crittenden showed a marked
      discolouring of the infiltrated areas of the leaf and decreased antibody
      expression. Co-expression of P19 also abolished antibody accumulation in crosses
      between N. tabacum cv. I-64 and Little Crittenden, indicating a dominant mode of
      inheritance for the observed P19-induced responses.

PMID- 22984969
TI  - Introduction to the special section.

PMID- 22984970
TI  - Coparenting interventions for fragile families: what do we know and where do we
      need to go next?
AB  - With a large and growing share of American families now forming outside of
      marriage, triangular infant-mother-father relationship systems in "fragile
      families" have begun to attract the interest of family scholars and clinicians. A
      relatively novel conceptualization has concerned the feasibility of intervening
      to support the development of a sustained and positive coparenting alliance
      between mothers and fathers who have not made an enduring relationship commitment
      to one another. At this point in time, there are very few published outcome
      studies of programs explicitly conceived to help build coparenting alliances in
      such families. This article reviews what we currently know from this evolving
      field of study, and from those related responsible fatherhood and marriage and
      relationship enhancement (MRE) initiatives that included any explicit targeting,
      strengthening, and assessment of fragile family coparenting in their designs. We
      summarize lessons learned thus far from Access and Visitation (AV) programs for
      non-residential fathers, from MRE programs for low-income, unmarried couples, and
      from newer programs for fragile families directly designed to target and support
      coparenting per se. We close with recommendations for charting this important new
      family process terrain.

PMID- 22984971
TI  - Coparenting and children's school readiness: a mediational model.
AB  - We examined the long-term direct and indirect links between coparenting
      (conflict, communication, and shared decision-making) and preschoolers' school
      readiness (math, literacy, and social skills). The study sample consisted of
      5,650 children and their biological mothers and fathers who participated in the
      Early Childhood Longitudinal Study-Birth Cohort. Using structural equation
      modeling and controlling for background characteristics, we found that our
      conceptual model of the pathways from coparenting to child outcomes is
      structurally the same for cohabiting and married families. Controlling for a host
      of background characteristics, we found that coparenting conflict and shared
      decision-making were negatively and positively, respectively, linked to
      children's academic and social skills and co-parental communication was
      indirectly linked to academic and social skills through maternal supportiveness.
      Coparenting conflict was also indirectly linked to children's social skills
      through maternal depressive symptoms. The overall findings suggest that for both
      cohabiting and married families, the context of conflicted coparenting may
      interfere with the development of children's social competencies and academic
      skills, whereas collaborative coparenting promotes children's school readiness
      because mothers are more responsive to their children's needs. These findings
      have implications for programs aimed at promoting positive family processes in
      cohabiting and married families.

PMID- 22984972
TI  - Cooperation, conflict, or disengagement? Coparenting styles and father
      involvement in fragile families.
AB  - This paper draws on information from the Fragile Families Study (N = 2,695) to
      examine how different coparenting styles emerge and are related to fathers'
      involvement with young children in a representative sample of unmarried parents.
      The results show that the quantity and quality of paternal involvement is
      significantly higher when unmarried parents establish a cooperative as opposed to
      a disengaged or conflicted coparenting style. Cooperative coparenting is less
      likely, however, when unmarried parents have separated after the birth or were
      never together as a couple, when fathers are unemployed or have other risk
      factors, when the child has a more difficult temperament, and when parents have
      fewer children together. This analysis also helps clarify previously equivocal
      findings concerning the relationship between coparenting conflict and paternal
      involvement. Regression results show that paternal involvement is not
      significantly different among parents with cooperative and mixed coparenting
      styles, indicating that when unmarried parents can work together and support each
      other's parenting efforts, even if they argue frequently while doing so, fathers
      remain more involved. At the same time, conflicted coparenting leads to a larger
      decrease in father involvement than disengaged coparenting. In the context of
      poorer-quality coparenting relationships, it was conflict that mattered for
      fathering, not just parents' inability to cooperate. Implications of these
      findings for parenting education programs are discussed.

PMID- 22984974
TI  - Prenatal representations of coparenting among unmarried first-time African
      American mothers.
AB  - Results of semistructured interviews with 45 pregnant unmarried first-time
      African American mothers indicated a wide range of expectancies concerning the
      coparenting relationship they would develop with others once their baby arrived.
      Most common coparenting systems projected by respondents involved maternal
      grandmothers and/or the babies' fathers, though other caregivers were explicitly
      anticipated in a smaller number of cases. Multiperson coparenting systems were
      the norm, and only 2 of 45 respondents anticipated that they would be entirely on
      their own with no coparental system whatsoever. Qualitative analyses of mothers'
      narratives about postbaby coparenting systems revealed five main constructions:
      having thought about and anticipating coparenting, positive in outlook; having
      thought about and anticipating coparenting, but with mild concerns (conflict,
      unreliability); having thought about coparenting and anticipating limited or no
      support; having thought about coparenting and anticipating significant conflict
      and nonsupport; and having not thought much about coparenting, being neither
      focused on nor worried about this issue. Illustrations of each of these types are
      provided, and directions for family science and practice are discussed.

PMID- 22984973
TI  - Low-income mothers as "othermothers" to their romantic partners' children:
      women's coparenting in multiple partner fertility relationships.
AB  - In this article, we investigated low-income mothers' involvement in multiple
      partner fertility (MPF) relationships and their experiences as "othermothers" to
      their romantic partners' children from previous and concurrent intimate unions.
      Othermothering, as somewhat distinct from stepmothering, involves culturally
      scripted practices of sharing parenting responsibilities with children's
      biological parents. We framed this investigation using this concept because
      previous research suggests that many low-income women practice this form of
      coparenting in their friend and kin networks. What is not apparent in this
      literature, however, is whether women unilaterally othermother their romantic
      partners' children from different women. How often and under what circumstances
      do women in nonmarital MPF intimate unions with men coparent their partners'
      children from other relationships? We explored this question using a modified
      grounded theory approach and secondary longitudinal ethnographic data on 256 low
      income mostly unmarried mothers from the Three-City Study. Results indicated that
      78% of the mothers had been or were involved in MPF unions and while most had
      othermothered the children of their friends and relatives, 89% indicated that
      they did not coparent their partners' children from any MPF relationship.
      Mothers' reasons for not doing so were embedded in: (a) gendered scripts around
      second families, or "casa chicas"; (b) the tenuous nature of pass-through MPF
      relationships; and (c) mothers' own desires for their romantic partners to child
      swap. Implications of this research for family science and practice are
      discussed.

PMID- 22984975
TI  - Those easily forgotten: the impact of emigration on those left behind.
AB  - Much has been written about the experiences and stresses of those who emigrate.
      By contrast, little attention has been paid to the experiences of those who stay
      behind-family members and friends who for various reasons do not to join their
      loved ones in the destination country. In this article, I describe the
      experiences of some South Africans whose families and friends have emigrated.
      This study forms part of a larger research project focusing on the impact of
      emigration on South African family life. Twenty-one participants were interviewed
      by means of a semistructured interview at least 6 months after one or more family
      member(s) and/or friend(s) left South Africa, to explore participants'
      experiences around their loved ones' emigration. A thematic analysis of the data
      reveals that those left behind experience various emotions, ranging from
      emotional ambivalence to anger and distress. Emigration is mostly experienced as
      a vast loss, almost akin to a "death," bringing about significant changes in
      social networks and relationships. The therapeutic significance of the findings
      for those working with emigrant families is also explored.

PMID- 22984976
TI  - Voices of dialogue and directivity in family therapy with refugees: evolving
      ideas about dialogical refugee care.
AB  - In this article, we reflect on our evolving ideas regarding a dialogical approach
      to refugee care. Broadening the predominant phased trauma care model and its
      engaging of directive expertise in symptom reduction, meaning making, and
      rebuilding connectedness, these developing dialogical notions involve the
      negotiation of silencing and disclosure, meaning and absurdity, hope and
      hopelessness in a therapeutic dialogue that accepts its encounter of cultural and
      social difference. In locating therapeutic practice within these divergent
      approaches, we argue an orientation on collaborative dialogue may operate
      together with notions from the phased trauma care model as heuristic background
      in engaging a polyphonic understanding of coping with individual and family
      sequelae of forced displacement. This locating of therapeutic practice, as
      informed by each perspective, invites us to remain present to fragments of
      therapeutic positioning that resonate power imbalance or appropriation in a
      therapeutic encounter imbued with a social context that silences refugees'
      suffering. In a clinical case analysis, we further explore these relational
      complexities of negotiating directive expertise and collaborative dialogue in the
      therapeutic encounter with refugee clients.

PMID- 22984977
TI  - The golden pig, reflections as ancestral blessings: the reflecting process in
      teaching family therapy.
AB  - This is an example of a postmodern, dialogical approach to teaching family
      therapy based on the work of such practitioners as Tom Andersen, Michael White,
      and Lynn Hoffman, among others. It demonstrates the way in which the reflecting
      process connects all of the participants in a web of meanings both educational
      and transformational. This particular consultation, which includes the author,
      her graduate students, the client, and guest participant Lynn Hoffman, ends with
      an unexpected ritual of intergenerational appreciation. Privileging the
      transcript, it is presented as a kind of theatre where the learning is revealed
      more through the dialogue than through authorial analysis. The experience is
      embedded in an "ethics of participation" (Hoffman, 1992) where social
      connectedness and attunement are key.

PMID- 22984978
TI  - The shift from monologue to dialogue in a couple therapy session: dialogical
      investigation of change from the therapists' point of view.
AB  - As part of a larger research project on couple therapy for depression, this
      qualitative case study examines the nature of dialogue. Drawing on Bakhtinian
      concepts, the investigation shows how the conversation shifts from a monologue to
      dialogue. Among the findings are: first, the process of listening is integral to
      the transforming experience. That is, the careful listening of the therapist can
      evoke new voices, just as the experience of one of the partners' "listening in"
      to the conversation between the other partner and the therapist can create
      movement and new trajectories. The latter is a qualitative difference between
      dialogic therapy with a couple and that with an individual. Second, the therapist
      not only acts as creative listener, but as the dialogue unfolds, actively
      contributes to meaning-making. Third, the study upholds having a team of
      researchers as a polyphonic forum and the usefulness of Bakhtinian concepts in
      clinical research on dialogue in multi-actor sessions.

PMID- 22984979
TI  - Computational fluid dynamics of a cylindrical nucleation flow reactor with
      detailed cluster thermodynamics.
AB  - Particle formation and growth with H(2)SO(4) molecules in an axially symmetric
      flow reactor was simulated with computational fluid dynamics. A warm (~310 K) gas
      containing H(2)SO(4) flows into a cooled section (296 K) that induces particle
      formation. The fluid dynamics gives flow fields, temperatures, and reactant and
      cluster distributions. Particle formation and growth are simulated with detailed
      H(2)SO(4) cluster kinetics with chemistry based on measured small cluster
      thermodynamics and on bulk thermodynamics for large clusters. Results show that
      particle number densities have power law dependencies on sulfuric acid of ~7, in
      accord with the thermodynamics of the cluster chemistry. The region where
      particle formation rates are largest has a temperature that is within 3 K of the
      wall. Additional simulations show that the H(2)SO(4) concentration in this region
      is 5 to 10 times greater than the measured H(2)SO(4): this information allows for
      direct comparisons of experiment and theory. Experiments where ammonia was added
      as a third nucleating species were simulated with a three-dimensional model.
      Ammonia was dispersed quickly and particle formation during this mixing was seen
      to be low. Downstream of the initial mixing region, however, ammonia greatly
      affected particle formation.

PMID- 22984980
TI  - Factors affecting diagnostic yield in needle biopsy for brain lesions.
AB  - INTRODUCTION: We analyse the factors that are associated with the diagnostic
      yield of needle brain biopsy. MATERIAL AND METHODS: We present a retrospective
      series of 124 consecutive biopsies in a 30-month period. Patients' demographics
      (age, gender), lesion topography (side, location, depth), lesion characteristics
      (histology, volume, radiological enhancement), type of biopsy procedure
      (freehand, ultrasound guided, frameless and frame-based stereotactic) and the use
      of intraoperative histologic examination were correlated with the diagnostic
      rate. Descriptive statistics and a nominal logistic regression model were used to
      evaluate the factors influencing diagnostic yield. RESULTS: 63 men and 61 women
      were included in the study with mean age 59.2 (range: 16-86). 55 were frame-based
      stereotactic biopsies, 33 were frameless stereotactic biopsies, 29 biopsies were
      performed under ultrasound guidance and 7 freehand. The diagnostic yield in our
      series is 93.5%. The gender, lesion topography, biopsy method, use of
      intraoperative histology and enhancement did not correlate with the diagnostic
      yield. Younger age had a negative impact on diagnostic yield. 6 out of 8
      inconclusive biopsies were in non-glial lesions (p < 0.05). The odds of obtaining
      a positive diagnosis increased sevenfold with every cc increase in lesion volume.
      CONCLUSION: The age of the patient, the volume and the histology of the brain
      lesion had an impact on the diagnostic yield of needle biopsy. None of the other
      factors significantly influenced the diagnostic rate.

PMID- 22984981
TI  - Surgical cannulation of the superior ophthalmic vein for the treatment of
      previously embolized cavernous sinus dural arteriovenous fistulas: serial studies
      and angiographic follow-up.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of
      transorbital puncture for the retreatment of previously embolized cavernous sinus
      dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV)
      approach. MATERIALS AND METHODS: During a 12-year period, 9 consecutive patients
      with previously embolized cavernous sinus DAVFs underwent retreatment via the
      transorbital SOV approach. RESULTS: All of the nine cases of previously embolized
      cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were
      conducted in all nine cases at the duration of 17-141 months (61.22 +/- 39.13
      months). No recanalization occurred during the follow-up period. A subtle ptosis
      appeared in two patients and disappeared in one of the two cases after a 4-year
      follow-up. One patient suffered from paroxysmal positional vertigo and bruit for
      nearly 2 years after the treatment, but the follow-up angiography demonstrated no
      recurrence. One patient had persistent visual impairment caused by the initial
      venous stasis retinopathy. One patient with a history of a procedure-related
      transient decrease in visual acuity had it return to the normal level. The
      remaining four cases had clear improvement in the ocular symptoms and became
      completely asymptomatic during the follow-up period. No patient worsened or
      developed new symptoms. CONCLUSION: The approach of surgical cannulation of the
      SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved
      feasible and efficient, especially when the transarterial and transfemoral venous
      approaches were inaccessible. However, if the SOV is not dilated enough or is
      located deeply in the orbit, transorbital venous puncture access may not be
      possible.

PMID- 22984982
TI  - Long-term outcomes of one-stage anterior debridement, bone grafting, and internal
      fixation for the treatment of lower cervical tuberculosis with kyphosis.
AB  - BACKGROUND: Patients with spinal deformities and nerve compression due to spinal
      tuberculosis often require surgical intervention. The objective of this study was
      to assess the long-term therapeutic effectiveness of one-stage anterior
      debridement, bone grafting, and internal fixation for lower cervical tuberculosis
      with kyphosis. METHODS: Twenty-one patients with lower cervical tuberculosis and
      cervical kyphosis received one-stage anterior debridement, autologous iliac bone
      grafting, and internal plate fixation. Patients were followed-up postoperatively
      for at least 5 years. Outcome measures included neck pain using Visual Analogue
      Scale (VAS) scores, Frankel classification of spinal cord injury, and Cobb angle
      of cervical kyphosis. RESULTS: Eighteen patients had lesions in 2 vertebrae and 3
      had lesions in 3 vertebrae. Cervical tuberculosis was cured in all patients. The
      mean preoperative VAS score for neck pain was 8 (range: 6-10), whereas the mean
      best postoperative VAS score was 0.6 (range: 0-3). Mean final VAS score was
      significantly higher than the best VAS score (2.14 vs. 0.62). Of the 13 patients
      with symptoms of spinal cord compression, 9 improved by 1 grade and 4 improved by
      2 grades according to Frankel classification at final follow-up. The mean
      preoperative Cobb angle of cervical kyphosis was 29 degrees  (range: 15 degrees 
      50 degrees ), whereas the mean postoperative Cobb angle at final follow-up was 
      1.8 degrees  (range: 2-7 degrees ). CONCLUSIONS: One-stage anterior debridement,
      bone grafting, and internal fixation can effectively remove lesions, decompress
      the nerve, reduce pain, and correct kyphosis in patients with cervical
      tuberculosis and associated kyphosis. Long-term postoperative outcomes were
      satisfactory.

PMID- 22984984
TI  - Theoretical analysis of the catalytic mechanism of Helicobacter pylori glutamate
      racemase.
AB  - One of the most challenging open key questions behind the stereoinversion of D
      glutamate and L-glutamate catalyzed by glutamate racemases is how those enzymes
      manage to generate the thermodynamically unfavorable reverse protonation state of
      the catalytic residue cysteine required for the proton abstraction from the alpha
      carbon of glutamate. In this paper, we have used molecular dynamics (MD)
      simulations with a molecular mechanics force field along with QM/MM calculations
      starting from the crystal structure and from different MD snapshots to study the
      enantiomeric conversion of D-glutamate to L-glutamate catalyzed by the
      Helicobacter pylori glutamate racemase. Our results show that structural
      fluctuations of the enzyme-substrate complex, represented by the different
      snapshots, lead to reaction paths with different features and fates. The whole
      reaction, when it occurs, involves four successive proton transfers in three or
      four different steps. In the first step, Asp7 assists the deprotonation of D
      glutamate by participating in general base catalysis with neutral Cys70 thiol. An
      analogous mechanism was previously found by some of us for the case of Bacillus
      subtilis glutamate racemase. This fact explains why that aspartate belongs to the
      group of strictly conserved residues.

PMID- 22984983
TI  - A pipeline for automated annotation of yeast genome sequences by a conserved
      synteny approach.
AB  - BACKGROUND: Yeasts are a model system for exploring eukaryotic genome evolution.
      Next-generation sequencing technologies are poised to vastly increase the number
      of yeast genome sequences, both from resequencing projects (population studies)
      and from de novo sequencing projects (new species). However, the annotation of
      genomes presents a major bottleneck for de novo projects, because it still relies
      on a process that is largely manual. RESULTS: Here we present the Yeast Genome
      Annotation Pipeline (YGAP), an automated system designed specifically for new
      yeast genome sequences lacking transcriptome data. YGAP does automatic de novo
      annotation, exploiting homology and synteny information from other yeast species
      stored in the Yeast Gene Order Browser (YGOB) database. The basic premises
      underlying YGAP's approach are that data from other species already tells us what
      genes we should expect to find in any particular genomic region and that we
      should also expect that orthologous genes are likely to have similar intron/exon
      structures. Additionally, it is able to detect probable frameshift sequencing
      errors and can propose corrections for them. YGAP searches intelligently for
      introns, and detects tRNA genes and Ty-like elements. CONCLUSIONS: In tests on
      Saccharomyces cerevisiae and on the genomes of Naumovozyma castellii and
      Tetrapisispora blattae newly sequenced with Roche-454 technology, YGAP
      outperformed another popular annotation program (AUGUSTUS). For S. cerevisiae and
      N. castellii, 91-93% of YGAP's predicted gene structures were identical to those
      in previous manually curated gene sets. YGAP has been implemented as a webserver
      with a user-friendly interface at http://wolfe.gen.tcd.ie/annotation.

PMID- 22984985
TI  - Occlusal support including that from artificial teeth as an indicator for health
      promotion among community-dwelling elderly in Japan.
AB  - AIM: The Eichner index (EI) is used to evaluate occlusal support. However, this
      index is based on existing natural tooth contact. This study aimed to establish
      whether a modified EI that included artificial teeth reflected individual oral
      condition of elderly people, and to clarify the relationship between this index
      and: (i) mental condition; (ii) physical condition; and (iii) physical function.
      METHODS: We recruited 286 people (145 men, 141 women) aged 65-79 years. They were
      divided into three groups by modified EI, and then underwent assessment of oral
      condition. After establishing that the index was clearly related to oral
      condition, we investigated psychological factors (satisfaction with life, self
      rated health and anxiety regarding falling), indicators of walking and balance
      (Timed Up & Go test [TUG] and one-leg standing balance), physical condition
      (higher-level functional capacity [HLFC]: instrumental activities of daily living
      [IADL], intellectual activity and social role; continuous walking over 15 min;
      and frequency of outings), and health history in the previous year (history of
      hospital admissions and falls). RESULTS: Modified EI was a good indicator of
      occlusal condition. The index was significantly correlated in men with
      satisfaction with life, TUG test, one-leg standing balance, overall HLFC and HLFC
      IADL, and in women with TUG test, one-leg standing balance and HLFC-Intellectual
      activity. CONCLUSION: The evaluation of occlusal support including that from
      artificial teeth is beneficial in the elderly as an indicator of health and oral
      function, in particular firm bite.

PMID- 22984986
TI  - Pathogen recognition in the human female reproductive tract: expression of
      intracellular cytosolic sensors NOD1, NOD2, RIG-1, and MDA5 and response to HIV-1
      and Neisseria gonorrhea.
AB  - PROBLEM: Expression patterns and regulation of cytosolic pattern recognition
      receptors (PRR) NOD-1, NOD-2, RIG-1, and MDA5 have not been elucidated in the
      human female reproductive tract (FRT). METHOD OF STUDY: Primary epithelial cells
      (EC) isolated from Fallopian tube (FT), endometrium (EM), cervix (Cx), and
      ectocervix (Ecx) were treated with estradiol, poly(I:C), Neisseria gonorrhea
      (GC), and HIV-1. PRR mRNA expressions were analyzed by Real-time RT-PCR.
      Conditioned media were analyzed for IL-8 by ELISA. RESULTS: EC from all FRT
      compartments constitutively expressed NOD1, NOD2, RIG-1, and MDA5 with highest
      levels expressed by FT. Stimulation with poly(I:C) resulted in upregulation of
      NOD2, RIG-1, and MDA5 in all FRT compartments and correlated with increased
      secretion of IL-8, whereas estradiol treatment had no effects. Exposure to GC and
      HIV-1 IIIB but not BaL resulted in selective upregulation of NOD2 and MDA5.
      CONCLUSION: PRR are expressed throughout the FRT and differentially regulated by
      poly(I:C), GC and HIV-1.

PMID- 22984988
TI  - The prevalence of disseminated Mycobacterium avium subsp. paratuberculosis
      infection in tissues of healthy ewes from a New Zealand farm with Johne's disease
      present.
AB  - AIM: To determine the prevalence of disseminated Mycobacterium avium subsp.
      paratuberculosis (Map) infection in healthy ewes in a flock with a history of
      clinical Johne's disease. METHODS: Twenty-four healthy ewes, from a large sheep
      and cattle farm with a history of clinical Johne's disease in the ewe flock, were
      randomly selected, euthanased, blood sampled, and examined at necropsy. BACTECTM
      radiometric culture for Map was performed on samples of faeces, ileum, mesenteric
      lymph node, biceps femoris muscle and mononuclear cells in peripheral blood.
      Serum antibody ELISA tests were performed. Histological sections and Ziehl
      Neelsen (ZN) stains of impression smears of ileum and mesenteric lymph node were
      examined for pathological lesions characteristic of Johne's disease and acid fast
      organisms (AFO). Indirect quantification of Map was performed, using BACTEC
      radiometric growth indices measuring the time taken for the production of
      (14)CO(2.) RESULTS: No histological evidence of Johne's disease or AFO was found
      in the ileum and mesenteric lymph nodes. Twelve of the 24 ewes (50%) had Map
      cultured from the ileum (n=6) and/or mesenteric lymph nodes (n=8) while none had
      Map cultured from the faeces, biceps femoris muscle or blood mononuclear cells.
      One of the 12 Map culture positive ewes was serum ELISA positive. The culture
      growth rates in liquid medium suggest low numbers of Map were present in the
      tissues of the culture positive ewes. CONCLUSION: Fifty per cent of clinically
      healthy ewes exposed to Map within a Johne's infected flock were Map culture
      positive in the ileum and/or mesenteric lymph node(s), while the ELISA was
      positive in 8% of those animals (n=1). There was no faecal shedding of Map and no
      Map was cultured from skeletal muscle or from blood mononuclear cells suggesting
      that systemic Map infection, defined as positive culture of Map from skeletal
      muscle and/or blood, may be uncommon in healthy mixed age ewes without clinical
      Johne's disease. CLINICAL RELEVANCE: ELISA serology detected 1 of 12 ewes
      infected with Map whilst none were detected from faecal BACTEC radiometric
      culture, suggesting biosecurity measures used to control the spread of Map may be
      of limited use. Map was not cultured from blood mononuclear cells or skeletal
      muscle, indicating that meat from healthy ewes, from farms where Johne's disease
      is present, is an unlikely source of Map exposure for humans. Further research is
      warranted to establish the prevalence and dissemination of Map in tissues outside
      the alimentary tract of healthy ewes from farms throughout New Zealand where Map
      is present.

PMID- 22984987
TI  - Discovery of diverse human dihydroorotate dehydrogenase inhibitors as
      immunosuppressive agents by structure-based virtual screening.
AB  - This study applied an efficient virtual screening strategy integrating molecular
      docking with MM-GBSA rescoring to identify diverse human dihydroorotate
      dehydrogenase (hDHODH) inhibitors. Eighteen compounds with IC(50) values ranging
      from 0.11 to 18.8 MUM were identified as novel hDHODH inhibitors that exhibited
      overall species-selectivity over Plasmodium falciparum dihydroorotate
      dehydrogenase (pfDHODH). Compound 8, the most potent one, showed low micromolar
      inhibitory activity against hDHODH with an IC(50) value of 0.11 MUM. Moreover,
      lipopolysaccharide-induced B-cell assay and mixed lymphocyte reaction assay
      revealed that most of the hits showed potent antiproliferative activity against B
      and T cells, which demonstrates their potential application as immunosuppressive
      agents. In particular, compound 18 exhibited potent B-cell inhibitory activity
      (IC(50) = 1.78 MUM) and presents a B-cell-specific profile with 17- and 26-fold
      selectivities toward T and Jurkat cells, respectively.

PMID- 22984989
TI  - High-resolution SNP array analysis of patients with developmental disorder and
      normal array CGH results.
AB  - BACKGROUND: Diagnostic analysis of patients with developmental disorders has
      improved over recent years largely due to the use of microarray technology. Array
      methods that facilitate copy number analysis have enabled the diagnosis of up to
      20% more patients with previously normal karyotyping results. A substantial
      number of patients remain undiagnosed, however. METHODS AND RESULTS: Using the
      Genome-Wide Human SNP array 6.0, we analyzed 35 patients with a developmental
      disorder of unknown cause and normal array comparative genomic hybridization
      (array CGH) results, in order to characterize previously undefined genomic
      aberrations. We detected no seemingly pathogenic copy number aberrations. Most of
      the vast amount of data produced by the array was polymorphic and non
      informative. Filtering of this data, based on copy number variant (CNV)
      population frequencies as well as phenotypically relevant genes, enabled
      pinpointing regions of allelic homozygosity that included candidate genes
      correlating to the phenotypic features in four patients, but results could not be
      confirmed. CONCLUSIONS: In this study, the use of an ultra high-resolution SNP
      array did not contribute to further diagnose patients with developmental
      disorders of unknown cause. The statistical power of these results is limited by
      the small size of the patient cohort, and interpretation of these negative
      results can only be applied to the patients studied here. We present the results
      of our study and the recurrence of clustered allelic homozygosity present in this
      material, as detected by the SNP 6.0 array.

PMID- 22984991
TI  - The role of clarity and blur in guiding visual attention in photographs.
AB  - Visual artists and photographers believe that a viewer's gaze can be guided by
      selective use of image clarity and blur, but there is little systematic research.
      In this study, participants performed several eye-tracking tasks with the same
      naturalistic photographs, including recognition memory for the entire photo, as
      well as recognition memory and personality ratings for individual people in the
      photos (Experiments 1-3). The results showed that fixations occurred more rapidly
      and frequently to a local region of clarity than to a comparable blurred region
      in all tasks, independent of the content of the photo in the local region, and
      even under instructions to look equally at both regions. However, this bias was
      reversed when the content of the photos was no longer task-relevant. In
      Experiment 4, participants located target regions defined by either clarity or
      blur. Fixations and manual responses were faster for blurred than for sharp
      targets. These findings imply that the saliency of both image clarity and image
      blur depends on viewers' goals. Focusing on photo content prioritizes regions of
      clarity whereas focusing on photo quality prioritizes attention to regions of
      blur.

PMID- 22984992
TI  - Primary visual cortex scales individual's perceived brightness with power
      function: inner psychophysics with fMRI.
AB  - Perceived brightness is well described by Stevens' power function (S. S. Stevens,
      1957, On the psychophysical law, Psychological Review, Vol. 64, pp. 153-181),
      with a power exponent of .33 (the cubic-root function of luminance). The power
      exponent actually varies across individuals, yet little is known about neural
      substrates underlying this individual difference. The present functional MRI
      study investigated how neural activation levels in the visual cortex serve to
      scale individual's subjective brightness. Participants rated brightness of a disk
      ranging from 1- to 100-cd/m2 luminance. Subjective brightness ratings showed an
      almost perfect log-linear dependence on luminance intensity, with the power
      exponent averaging .32. The fMRI results showed that activity in the bilateral
      primary visual cortex along with the calcarine sulcus (also known as Brodmann's
      area 17 and V1) increased log-linearly with physical luminance, showing average
      power exponents of .32 and .27 in the left and right hemispheres, respectively.
      There were substantial individual variations in the power function exponents for
      both subjective brightness ratings (.14 to .46) and primary visual cortex
      activation (.12 to .55). An important finding was that 2 power exponents were
      closely correlated (r = .62). Subjective brightness ratings and primary visual
      cortex activation were both better correlated with stimulus luminance than
      stimulus contrast (at the border of the stimulus). These results suggest that
      primary visual cortex activation can scale individual's subjective brightness in
      accordance with Stevens' power law.

PMID- 22984990
TI  - Dissociating stimulus-set and response-set in the context of task-set switching.
AB  - The primary aim of the present research was to determine how stimulus-set and
      response-set components of task-set contribute to switch costs and conflict
      processing. Three experiments are described wherein participants completed an
      explicitly cued task-switching procedure. Experiment 1 established that task
      switches requiring a reconfiguration of both stimulus- and response-set incurred
      larger residual switch costs than task switches requiring the reconfiguration of
      stimulus-set alone. Between-task interference was also drastically reduced for
      response-set conflict compared with stimulus-set conflict. A second experiment
      replicated these findings and demonstrated that stimulus- and response-conflict
      have dissociable effects on the "decision time" and "motor time" components of
      total response time. Finally, a third experiment replicated Experiment 2 and
      demonstrated that the stimulus- and response- components of task switching and
      conflict processing elicit dissociable neural activity as evidence by event
      related brain potentials.

PMID- 22984993
TI  - Evaluating SKI as a candidate gene for non-syndromic cleft lip with or without
      cleft palate.
AB  - Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most
      common of all congenital malformations and has a multifactorial etiology.
      Findings in mice suggest that the v-ski sarcoma viral oncogene homolog (SKI) gene
      is a candidate gene for orofacial clefting. In humans, a significant association
      between rs2843159 within SKI and NSCL/P has been reported in patients from the
      Philippines and South America. In the South American patients, the association
      was driven by the subgroup of patients with non-syndromic cleft lip only (NSCLO).
      Here we investigated the association with rs2843159 in a Mayan Mesoamerican
      population (172 NSCL/P patients and 366 controls). In addition, we analyzed the
      phenotypic subgroups NSCLO and non-syndromic cleft of lip and palate (NSCLP). A
      trend towards association between rs2843159 and NSCL/P was observed in the Mayan
      cohort (P = 0.097), and we found a stronger association in the NSCLP subgroup (P
      = 0.072) despite a limited sample size. To investigate whether other common
      variants within the SKI gene contribute to NSCL/P susceptibility in European and
      Asian populations, we also analyzed genotypic data from two recent genome-wide
      association studies using set-based statistical approaches. These analyses
      detected a trend toward association in the European population. Our data provide
      limited support for the hypothesis that common SKI variants are susceptibility
      factors for NSCL/P.

PMID- 22984994
TI  - A case-control study of the association between tooth-development gene
      polymorphisms and non-syndromic hypodontia in the Chinese Han population.
AB  - Hypodontia is one of the most common anomalies of human dentition. Recent genetic
      studies provide information on a number of genes related to both syndromic and
      non-syndromic forms of hypodontia. Fifty putative single nucleotide polymorphisms
      (SNPs) in 20 genes that play important roles in tooth development were selected,
      and a case-control study was conducted in 273 subjects with hypodontia (cases)
      and 200 subjects without hypodontia (controls). DNA was obtained from samples of
      whole blood or saliva. Genotyping was performed by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). A
      significant difference was observed, between subjects with non-syndromic
      hypodontia and controls, in the allele and genotype frequencies of two markers
      [rs929387 of GLI family zinc finger 3 (GLI3) and rs11001553 of Dickkopf-related
      protein 1 (DKK1)]. Similar results were observed in a subgroup analysis of test
      subjects (stratified by gender or missing tooth position). However, this analysis
      showed no significant difference in the haplotype distribution between the
      controls and the affected subjects. These data demonstrate an association between
      some SNPs in tooth development-associated genes and sporadic non-syndromic
      hypodontia in Chinese Han individuals. This information may provide further
      understanding of the molecular mechanisms of tooth agenesis. Furthermore, these
      genes can be regarded as candidates for mutation detection in individuals with
      tooth agenesis.

PMID- 22984995
TI  - Elevated expression of calcineurin subunits during active mineralization of
      developing mouse molar teeth.
AB  - Calcineurin is a Ca(2+) /calmodulin-dependent protein phosphatase consisting of
      two subunits - catalytic subunit A (CnA) and regulatory subunit B (CnB) - and
      plays a critical role in transducing Ca(2+)  signals into cellular responses. In
      this study, we investigated the expression of calcineurin in the mouse developing
      tooth. In-situ hybridization detected mRNAs for the CnAalpha and CnAbeta isoforms
      of CnA and for the CnB1 isoform of CnB in the upper molar tooth germ at embryonic
      day 15. Immunohistochemistry with antibodies specific for CnAalpha, CnAbeta, and
      CnB1 showed strong immunoreactivity of these proteins in secretory-stage
      ameloblasts and in odontoblasts during dentin formation. CnAbeta and CnB1 were
      strongly immunoreactive in ruffle-ended ameloblasts at the enamel-maturation
      stage. In ameloblasts and odontoblasts, we also noted different subcellular
      distributions of CnAalpha and CnAbeta. From these data, temporal profiles of
      calcineurin expression appear to correlate with active mineralization in tooth
      development. Furthermore, the distinct subcellular distribution of the two CnA
      subunits may reflect their distinct substrates or responsive sites within single
      cells, thus contributing to the diversity of calcineurin-dependent cellular
      responses during active tooth mineralization.

PMID- 22984997
TI  - Glutamate control of pulpal blood flow in the incisor dental pulp of the rat.
AB  - Glutamate is present in primary sensory afferents innervating the dental pulp and
      is known to exert vasoactive effects. The aims of this study were (i) to assess
      pulpal blood flow (PBF) after glutamate infusion in the dental pulp and (ii) to
      observe the distribution of glutamatergic nerve fibers expressing the vesicular
      transporters of glutamate (VGluT). The PBF was monitored with laser Doppler
      flowmetry before and after glutamate (0.5 M) infusion in the dental pulp vs.
      saline infusion. Immunochemistry for VGluT1, 2, and 3 was performed in addition
      to immunochemistry for the vascular and neuronal markers smooth-muscle actin
      (SMA), isolectin B4 (IB4), and calcitonin gene-related peptide (CGRP). Glutamate
      infusion resulted in a PBF increase that lasted for 60 s. Positive immunolabeling
      was observed for the three glutamate transporters, but was more pronounced for
      VGluT3. Moreover, VGluT3 immunoreactivity was observed within nerve fibers
      entering the dental pulp and terminating at the periphery and at the vicinity of
      odontoblasts. Also, VGluT3 was colocalized with the vascular marker SMA, and in
      some nerve fibers with IB4, but not with CGRP. This study provides support for a
      control of dental pulp microcirculation by neurons expressing VGluT3.

PMID- 22984996
TI  - Distribution of carcinoembryonic antigen-related cellular adhesion molecules in
      human gingiva.
AB  - Carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs) are
      glycoproteins produced in epithelial, endothelial, lymphoid, and myeloid cells.
      Carcinoembryonic antigen-related cellular adhesion molecules mediate cell-cell
      contact and host-pathogen interactions. The aims of this study were to map the
      distribution and examine the regulation of CEACAMs in human gingival sites.
      Quantitative real-time PCR performed on human gingival biopsies from
      periodontitis sites revealed mRNA coding for CEACAM1, -5, -6, and -7.
      Immunohistochemistry showed that CEACAMs were not found in oral gingival
      epithelium, except for CEACAM5 in periodontitis. Carcinoembryonic antigen-related
      cellular adhesion molecules 1, 5, and 6 were present in the oral sulcular
      epithelium of periodontitis but not in that of healthy gingiva. In junctional
      epithelium, all three molecules were present in healthy gingiva, but in
      periodontitis only CEACAM1 and -6 were detected. Staining for CEACAM1 and -6 was
      also seen in the inflammatory cell infiltrate in periodontitis. No staining for
      CEACAM7 was found. Proinflammatory mediators, including lipopolysaccharide (LPS),
      tumour necrosis factor-alpha (TNF-alpha)/interleukin-1beta (IL-1beta), and
      interferon-gamma (IFN-gamma), increased the expression of CEACAM1 and CEACAM6
      mRNAs in cultured human oral keratinocytes. CEACAM1 and CEACAM6 mRNAs were also
      strongly up-regulated upon stimulation with lysophosphatidic acid. In conclusion,
      the distribution of different CEACAMs was related to specific sites in the
      gingiva. This might reflect different functional roles in this tissue.

PMID- 22984998
TI  - Immunomodulation of dendritic cells differentiated in the presence of nicotine
      with lipopolysaccharide from Porphyromonas gingivalis.
AB  - Tobacco smoking is a significant risk factor for periodontal diseases. Nicotine,
      one of the most studied constituents in cigarette smoke, is thought to modify
      immune responses. Dendritic cells (DCs), which are key mediators between innate
      and adaptive immunity, stimulate naive T cells to differentiate to effector T
      cell subsets that may be actively involved in the immunopathogenesis of
      periodontal diseases. In this study, we evaluated the effects of nicotine and
      lipopolysaccharide (LPS) from Porphyromonas gingivalis, alone and in combination,
      on the functions of human monocyte-derived DCs to elucidate the mechanism of
      tissue destruction of smoking-associated periodontal diseases. P. gingivalis LPS
      stimulated DCs differentiated with nicotine (NiDCs) induced lower T-cell
      proliferation and human leukocyte antigen (HLA)-DR expression, but elevated
      expression of programmed cell death ligand 1. Additionally, NiDCs impaired
      interferon-gamma production but maintained interleukin (IL)-5 and IL-10
      production in co-cultured T cells. Furthermore, NiDCs produced lower levels of
      proinflammatory cytokines compared with DCs differentiated in the absence of
      nicotine. Interestingly, NiDCs preferentially produced the T helper 2 (Th2)-type
      chemokines macrophage chemotactic protein-1 and macrophage-derived chemokine.
      These results suggest that the presence of nicotine during differentiation of DCs
      modulates the immunoregulatory functions of P. gingivalis LPS-stimulated DCs.

PMID- 22984999
TI  - Fluoridated toothpaste: usage and ingestion of fluoride by 4- to 6-yr-old
      children in England.
AB  - Fluoridated toothpaste is effective for dental caries control, yet may be a risk
      factor for dental fluorosis. This study aimed to quantify fluoride ingestion from
      toothpaste by children and to investigate the effects of age, gender, and social
      class on the amount of fluoride ingested per toothbrushing session. Sixty-one
      children, 4-6 yr of age, were recruited: 38 were from low socio-economic (LSE)
      areas of Newcastle, UK, and 23 were from high socio-economic (HSE) areas of
      Newcastle, UK. All expectorated saliva, rinse water (if used), and residual
      toothpaste were collected after brushing at home and were analysed for fluoride.
      Of the children, 74% and 69% from HSE and LSE areas, respectively, claimed that
      they brushed twice per day. The mean (SD) weight of toothpaste dispensed was 0.67
      (0.36) g. The mean (SD) amount of fluoride ingested per toothbrushing session and
      per day was 17.0 (14.7) and 29.3 (32.8) MUg kg(-1) of body weight, respectively.
      Daily fluoride intake per kilogram of body weight did not differ significantly
      between children from LSE and HSE areas. Fluoride intake per toothbrushing
      session was significantly influenced by weight of toothpaste, its fluoride
      concentration, and the child's age. Whilst the average amount of toothpaste used
      per toothbrushing session was more than twice the recommended amount (of 0.25 g),
      only one child had a daily fluoride intake that exceeded the tolerable upper
      intake level of 0.1 mg kg(-1) of body weight for this age group.

PMID- 22985000
TI  - Change in self-reported oral health in relation to use of dental services over 2
      yr.
AB  - To investigate change in oral health in relation to use of dental services, a
      random sample of 45- to 54-yr-old subjects from Adelaide, South Australia, was
      surveyed in 2004-2005 (n = 986, response rate = 44.4%). Service use and a global
      oral-health transition (GOHT) statement were collected over 2 yr. Worsening in
      oral health was reported from the GOHT statement by 25% of persons, while
      improvement was reported by 30%. Prevalence ratios (PRs, 95% CI), adjusted for
      sex, education, health card status, and toothbrushing, showed that worsening oral
      health was inversely associated with dental visiting (PR = 0.5, 0.4-0.7) and with
      scaling and cleaning services (PR = 0.6, 0.4-0.9), whereas extractions (PR = 2.3,
      1.6-3.4) and dentures (PR = 2.2, 1.3-3.7) were associated with a higher
      prevalence of worsening. Scaling and cleaning services were associated with
      improvement in oral health (PR = 1.5, 1.01-2.3), while endodontic services were
      inversely associated with improvement (PR = 0.3, 0.1-0.9). Worsening in oral
      health was associated with extractions and dentures and was inversely associated
      with visiting and preventive care. Improvement in oral health was associated with
      preventive care and was inversely associated with endodontic treatment.

PMID- 22985001
TI  - Effect of a school-based oral health-education program on Iranian children:
      results from a group randomized trial.
AB  - Parents and school staff play important roles in promoting children's oral
      health. Our study goals were to investigate whether an intervention targeting
      parents and school staff can improve the oral-health behavior and oral-health
      status of schoolchildren. Three-hundred and ninety-two schoolchildren in six
      schools in Tehran participated in a group randomized trial from September 2010 to
      March 2011. Schools were randomly allocated into three groups: comprehensive,
      student, and control. Intervention in the comprehensive group consisted of
      strategies to encourage children, their parents, and school staff to increase the
      frequency of toothbrushing and flossing. In the student group, the intervention
      targeted only children. The control group received no intervention. The primary
      outcome was change in oral-health behaviors (brushing and flossing), while the
      secondary outcomes were changes in oral hygiene and Community Periodontal indices
      and in Health Belief Model components. Multilevel modeling was employed for data
      analyses. Students who were in the comprehensive intervention group brushed and
      flossed significantly more frequently compared with those in the student
      intervention group. Although students' gingival health improved significantly in
      the comprehensive intervention group, such significant improvement was not seen
      in the student group. In conclusion, promising results are seen when the oral
      health education targets both school and home settings.

PMID- 22985002
TI  - Prevalence, severity, and clinical determinants of oral impacts in older people
      in Bosnia and Herzegovina.
AB  - This study aimed to assess the prevalence and the severity of oral impacts and
      the relationships between oral health-related quality of life (OHRQoL) and
      clinical measures of oral function in a sample of older adults in Bosnia. The
      sample comprised 261 community-dwelling adults of >=65 yr of age. Participants
      were randomly drawn from three senior day-centres for elderly people. Data were
      collected using clinical examination and a questionnaire. The OHRQoL was assessed
      through the Oral Impacts on Daily Performances (OIDP) measure, in terms of the
      prevalence, intensity, and extent of oral impacts. Overall, 55.2% reported at
      least one oral impact in the last 6 months. Difficulty eating (43.3%) and
      difficulty speaking (34.1%) were the most common impacts. These were also the
      most severely affected performances, while 'going out' and 'enjoying the contact
      of other people' were the least severe. A higher number of natural teeth, natural
      occluding pairs, and anterior and posterior occluding pairs were all
      significantly associated with a lower prevalence of oral impacts and correlated
      with the OIDP score, even after adjusting for sociodemographic factors. The
      prevalence of oral impacts was high and there was a strong and consistent
      association between OHRQoL and clinical dental indicators of function.

PMID- 22985003
TI  - Molecular structural analysis of carious lesions using micro-Raman spectroscopy.
AB  - In clinical situations carious dentine tissues can be discriminated by most
      caries fluorescence detection tools, including a new fluorescence intra-oral
      camera. The objectives of this study were: (i) to analyze the Raman spectra of
      sound, carious, and demineralized dentine, (ii) to compare this spectral analysis
      with the fluorescence variation observed when using a fluorescence camera, and
      (iii) to evaluate the involvement of the Maillard reaction in the fluorescence
      variations. The first positive hypothesis tested was that the fluorescence of
      carious dentine obtained using a fluorescence camera and the Raman spectra
      variation were closely related. The second was that the variation of fluorescence
      could be linked with the Maillard reaction. Sound dentine, sound dentine
      demineralized in aqueous nitric acid solution, carious soft dentine, sound
      dentine demineralized in lactic acid solution, sound dentine demineralized in
      aqueous nitric acid solution and immersed in methylglycoxal solution, and sound
      dentine demineralized in aqueous nitric acid solution and immersed in
      methylglycoxal and glucose solutions, were studied using micro-Raman
      spectroscopy. Modifications in the band ratio of amide, phosphate, and carbonate
      were observed in the decayed and demineralized groups compared with the sound
      dentine group. The results indicate that a close relationship exists between the
      Maillard reaction and fluorescence variation.

PMID- 22985004
TI  - Sodium chloride and potassium sorbate: a synergistic combination against
      Enterococcus faecalis biofilms: an in vitro study.
AB  - Incomplete disinfection of the root canal system is a major cause of post
      treatment disease. This study aimed to investigate the disinfecting property of
      organic acid salts and sodium chloride (NaCl), in a double-hurdle strategy, on
      Enterococcus faecalis biofilms. First of all, the high-throughput resazurin
      metabolism assay (RMA) was used to test a range of organic acid salts. Then, to
      gain more insight into the efficacy of sorbate salt solutions, 48-h E. faecalis
      biofilms were evaluated in colony-forming unit (CFU) assays. Chlorhexidine (CHX)
      and calcium hydroxide [Ca(OH)(2) ] were tested in parallel as controls. Sorbate
      salt produced the largest and most significant reduction of fluorescence
      intensity in the RMA assay. Neither NaCl nor potassium sorbate (KS) alone induced
      a clinically relevant reduction of CFU counts after 1 h. Surprisingly, the
      combination of the two in a single solution had a synergistic effect on the
      inactivation of E. faecalis. Potassium sorbate amplified the efficacy of NaCl. Of
      the salts tested, NaCl with KS eradicated E. faecalis biofilms within 1 h. This
      study showed that the double-hurdle strategy indeed leads to synergistic efficacy
      and is a possible next step in the complete disinfection of endodontic
      infections.

PMID- 22985005
TI  - Influence of surface properties of resin-based composites on in vitro
      Streptococcus mutans biofilm development.
AB  - The aim of this in vitro study was to evaluate the influence of physicochemical
      surface properties of resin-based composites on Streptococcus mutans biofilm
      formation. Specimens were prepared from each of four resin-based composites by
      polymerization against Mylar strips. Half of the number of specimens received no
      further surface treatment, whereas the other half were subjected to a polishing
      treatment. Surface roughness (SR) and topography were assessed using profilometry
      and atomic force microscopy. Surface free-energy (SFE) was determined, and the
      chemical surface composition was analysed by X-ray photoelectron spectroscopy
      (XPS). S. mutans biofilms were formed on the surface of the resin-based composite
      specimens for either 48 or 96 h using an artificial mouth system (AMS). Polishing
      caused a significant decrease in SFE, and XPS analysis indicated an increase of
      surface silicon and a decrease of surface carbon. Only for Grandio was a
      significant increase in SR identified after polishing, which was probably related
      to the higher concentration of filler particles on its surface. Significantly
      less S. mutans biofilm formation was observed on polished resin-based composites
      than on unpolished resin-based composites. These results indicate that the
      proportions of resin matrix and filler particles on the surface of resin-based
      composites strongly influence S. mutans biofilm formation in vitro, suggesting
      that minimization of resin matrix exposure might be useful to reduce biofilm
      formation on the surface of resin-based composites.

PMID- 22985007
TI  - Considerations on personality, quality of life, and oral health.

PMID- 22985006
TI  - Influence of periodontal ligament simulation and splints on strains developing at
      the cervical area of a tooth crown.
AB  - Many in vitro tooth models do not incorporate periodontal ligament (PDL)
      simulation. This study presents the influence of physiologically loaded occlusal
      splints on cervical strains in a model incorporating roots and PDL. Four sets (N
      = 10) of occlusal splints differing in material (hard/soft) and location
      (upper/lower) were prepared for first maxillary and mandibular anatomic molars.
      Two strain gauges were bonded to the buccal and lingual aspects of the lower
      molar. Teeth were embedded in acrylic resin with/without a PDL-simulating
      material. Force vs. strain data were acquired during loading and the maximal
      strains at 500 N were analyzed. When PDL was incorporated into the model without
      splints, buccal compressive strains were significantly decreased. Usage of a soft
      splint resulted in compressive strains on both tooth aspects. Usage of a hard
      splint on the lower tooth resulted in higher compressive strains on the lingual
      side compared with the buccal side, whereas usage of this splint on the upper
      tooth resulted in tensile strains on the lingual side. Bending towards the buccal
      side occurred when the splints were located on the upper tooth. Soft splints
      reduce buccal bending, but do not reduce cervical strains. Periodontal ligament
      stimulation materials should therefore be incorporated in models involving teeth.

PMID- 22985009
TI  - Host preferences of Palaearctic Culicoides biting midges: implications for
      transmission of orbiviruses.
AB  - Feeding success depends on host availability, host defensive reactions and host
      preferences. Host choice is a critical determinant of the intensity at which
      pathogens are transmitted. The aim of the current study was to describe host
      preferences of Palaearctic Culicoides species (Diptera: Ceratopogonidae)
      Latreille using traps baited with the five different host species of poultry,
      horse, cattle, sheep and goat. Collections were carried out nightly in July and
      August 2009 in western France with three replicates of a 5 * 5 randomized Latin
      square (five sites, five hosts). Moreover, an ultraviolet (UV) light/suction trap
      was operated during host-baited collections to correlate Culicoides biting rates
      and UV light/suction trap catches. A total of 660 Culicoides belonging to 12
      species, but comprised mainly of Culicoides scoticus Downes and Kettle,
      Culicoides dewulfi Goetghebuer and Culicoides obsoletus Meigen, were collected on
      animal baits. Abundance was highest for the horse, which accounted for 95% of all
      Culicoides caught, representing 10 species. The horse, the largest bait, was the
      most attractive host, even when abundance data were corrected by weight, body
      surface or Kleiber's scaling factor. Culicoides obsoletus was the only dominant
      species attracted by birds. Both C. scoticus and C. dewulfi were collected mainly
      from the upper body of the horse. Finally, the quantification of host preferences
      allows for discussion of implications for the transmission of Culicoides-borne
      pathogens such as bluetongue virus. 

PMID- 22985010
TI  - After you: conversations between patients and healthcare professionals in
      planning for end of life care.
AB  - BACKGROUND: This study explores with patients, carers and health care
      professionals if, when and how Advance Care Planning conversations about
      patients' preferences for place of care (and death) were facilitated and
      documented. METHODS: The study adopted an exploratory case study design using
      qualitative interviews, across five services delivering palliative care to cancer
      and non-cancer patients within an urban and rural English region. The study
      recruited 18 cases made up of patients (N = 18; 10 men; 8 women; median age 75);
      nominated relatives (N = 11; 7 women; 4 men; median age 65) and healthcare
      professionals (N = 15) caring for the patient. Data collection included: 18
      initial interviews (nine separate interviews with patients and 9 joint interviews
      with patients and relatives) and follow up interviews in 6 cases (involving a
      total of 5 patients and 5 relatives) within one year of the first interview. Five
      group interviews were conducted with 15 healthcare professionals; 8 of whom also
      participated in follow up interviews to review their involvement with patients in
      our study. RESULTS: Patients demonstrated varying degrees of reticence, evasion
      or reluctance to initiate any conversations about end of life care preferences.
      Most assumed that staff would initiate such conversations, while staff were often
      hesitant to do so. Staff-identified barriers included the perceived risks of
      taking away hope and issues of timing. Staff were often guided by cues from the
      patient or by intuition about when to initiate these discussions. CONCLUSIONS:
      This study provides insights into the complexities surrounding the initiation of
      Advance Care Planning involving conversations about end of life care preferences
      with patients who are identified as having palliative care needs, in particular
      in relation to the risks inherent in the process of having conversations where
      mortality must be acknowledged. Future research is needed to examine how to
      develop interventions to help initiate conversations to develop person centred
      plans to manage the end of life.

PMID- 22985011
TI  - Depression and adolescent sexual activity in romantic and nonromantic relational
      contexts: a genetically-informative sibling comparison.
AB  - Adolescent dating and sexual activity are consistently associated with risk for
      depression, yet the pathways underlying this association remain uncertain. Using
      data on 1,551 sibling pairs (ages 13-18) from the National Longitudinal Study of
      Adolescent Health, the current study utilized a sibling comparison design to
      assess whether adolescent dating, sexual intercourse with a romantic partner, and
      sexual intercourse with a nonromantic partner were associated with higher levels
      of depressive symptoms independent of familial factors. Results indicated that
      adolescent dating, in and of itself, was not associated with depressive symptoms.
      The association between depressive symptoms and sexual activity with a romantic
      partner was fully accounted for by between-family genetic and shared
      environmental confounds. In contrast, sexual activity with a nonromantic partner
      was significantly associated with both mean levels of depressive symptoms and
      clinically severe depression, even within sibling dyads. This relationship was
      greater for younger adolescents (<15 years). These results are consistent with a
      growing body of research demonstrating that relationship contexts may be critical
      moderators of the psychosocial aspects of adolescent sexual experiences.

PMID- 22985012
TI  - Genetic overlap between personality and risk for disordered gambling: evidence
      from a national community-based Australian twin study.
AB  - Using data from a large Australian twin sample we examined the extent to which
      genetic variation in the Big Three personality dimensions (positive emotionality,
      negative emotionality, and constraint) and their lower-order components explained
      genetic variation in the risk for disordered gambling (DG) among men and women.
      Genetic influences contributing to individual differences in normal-range
      personality traits explained over 40% of the genetic risk for DG, with a larger
      contribution among women than among men. The largest and most robust
      contributions came from the higher-order personality dimension of negative
      emotionality and its two lower-order dimensions of alienation and aggression.
      Surprisingly, low self-control was associated with the genetic risk for DG only
      among women, and risk-taking/sensation-seeking did not explain genetic risk for
      DG in either sex. The results of this study have implications for the causes of
      comorbidity between DG and other psychiatric disorders, the search for genes
      associated with DG risk, and the possibility of sex differences in the etiology
      of DG. Using a broad-band inventory of personality supports the conclusion that
      there probably is a substantial proportion of genetic variation in DG that cannot
      be explained by individual differences in personality.

PMID- 22985013
TI  - Acute exercise attenuates negative affect following repeated sad mood inductions
      in persons who have recovered from depression.
AB  - Identifying factors that may protect individuals from developing Major Depressive
      Disorder (MDD) in the face of stress is critical. In the current study we
      experimentally tested whether such a potentially protective factor, engaging in
      acute exercise, reduces the adverse effects of repeated sad mood inductions in
      individuals who have recovered from depression. We hypothesized that recovered
      depressed participants who engage in acute exercise report a smaller increase in
      negative affect (NA) and a smaller decrease in positive affect (PA) when exposed
      to a repeated sad mood induction (i.e., habituation), whereas participants who do
      not exercise show sensitization (i.e., increased NA and decreased PA in response
      to a repeated adverse stimulus). Forty-one women recovered from MDD and 40
      healthy control women were randomly assigned to either exercise for 15 minutes or
      quiet rest. Afterward, participants were exposed to two sad mood inductions and
      reported their levels of affect throughout the study. Recovered depressed
      participants who had not exercised exhibited higher NA after the second sad mood
      induction, a finding consistent with sensitization. In contrast, both recovered
      depressed participants who had engaged in acute exercise and healthy control
      participants showed no increase in NA in response to the repeated sad mood
      induction. Participants who exercised reported higher PA after the exercise bout;
      however, our hypothesis concerning reported PA trajectories following the sad
      mood inductions was not supported. Results suggest that exercise can serve as a
      protective factor in the face of exposure to repeated emotional stressors,
      particularly concerning NA in individuals who have recovered from depression.

PMID- 22985014
TI  - Impulsivity and response modulation deficits in psychopathy: evidence from the
      ERN and N1.
AB  - The response modulation hypothesis of psychopathy states that psychopaths'
      inability to adapt their behavior to changing circumstances results from an
      inability to process peripheral cues in the midst of a dominant response. The
      current study examined this relationship between psychopathic traits and response
      modulation using a lexical decision stop signal task and event-related potentials
      to assess deficits in stimulus and error processing. Overall, the impulsive
      antisocial (IA) factor of psychopathy was related to poor behavioral performance,
      particularly in relation to response inhibition. Additionally, IA was related to
      reduced processing of the stop signal itself as well as subsequent inhibition
      errors. This deficient processing of the stop signal was found to significantly
      mediate the relationship among IA, behavioral performance, and the processing of
      inhibition errors, indicating that a deficit in processing peripheral cues may be
      responsible for subsequent behavioral and error processing deficits in IA.

PMID- 22985015
TI  - Facets of negative affect prior to and following binge-only, purge-only, and
      binge/purge events in women with bulimia nervosa.
AB  - Ecological momentary assessment (EMA) data suggest that global negative affect
      (NA) increases prior to and decreases following episodes of binge eating and
      purging, providing support for the affect regulation model of BN. The current
      study examined whether facets of NA are differentially related to bulimic
      behaviors. Women with bulimia nervosa (BN; n = 133) completed a 2-week EMA
      protocol. Momentary assessments of 4 facets of NA (Fear, Guilt, Hostility, and
      Sadness) were derived from the PANAS subscales. Trajectories of the NA facets
      were modeled prior to and following binge-only, purge-only, and binge/purge
      events. Fear, Guilt, Hostility, and Sadness increased prior to and decreased
      following binge-only and binge/purge events. The same results were found for
      purge-only events, with the exception that Hostility did not increase
      significantly prior to purging. Notably, ratings of Guilt were higher than those
      of Fear, Hostility, and Sadness at the time of binge-only and binge/purge events.
      Furthermore, post hoc analyses demonstrate that Guilt increased prior to and
      decreased following the 3 behavior types, even after controlling for Fear,
      Hostility, and Sadness. These results provide further support for the affect
      regulation model of BN and also suggest that guilt may be particularly important
      to the pathology of BN.

PMID- 22985016
TI  - A null effect of target's velocity in the visual representation of motion with
      schizophrenic patients.
AB  - When people are shown a moving object that suddenly disappears and are instructed
      to locate its vanishing position, systematic errors in the direction of motion
      and in the direction of gravity are usually observed. Entitled, respectively,
      Representational Momentum (RepMo) and Representational Gravity, these phenomena
      seem to be influenced by low-level perceptual mechanisms and high-level cognitive
      aspects alike. Although being widely acknowledged that schizophrenic patients
      reveal several deficits in the perception and processing of motion, no study to
      date has explored these behavioral spatial mislocalizations of smoothly moving
      targets. The present study reports two experiments intending to fill this gap.
      The outcomes systematically disclosed a null effect of target's velocity for
      schizophrenic patients, a well established determinant of RepMo's magnitude with
      nonpsychiatric populations. No other variables (implied mass and motion
      direction) revealed this dissociation between the groups. The results are
      discussed within the distinction of kinematic and dynamic variables, with
      schizophrenic patients revealing a deficit in the processing of the former, and a
      link with dysfunctional smooth pursuit eye movements is suggested.

PMID- 22985017
TI  - Analysis of monoaminergic genes, childhood abuse, and dimensions of psychopathy.
AB  - Psychopathy is a multidimensional construct characterized by an interpersonally
      manipulative and emotionally detached personality profile that differentiates it
      from other antisocial syndromes. Previous research with youth has linked the long
      allele of the serotonin transporter gene in the presence of environmental stress
      with the interpersonal and affective traits of psychopathy, but these
      relationships have yet to be examined in relation to adult psychopathy.
      Consequently, we examined how serotonin transporter (5-HTTLPR) polymorphisms,
      monoamine oxidase-A (MAO-A) variants, and childhood abuse measured with the
      Childhood Trauma Questionnaire relate to dimensions of psychopathy in a forensic
      sample of 237 men with elevated levels of environmental adversity. We found that
      the emotional deficits characterizing the affective factor of psychopathy, as
      measured by the Psychopathy Checklist: Screening Version, were highest among
      carriers of the 5-HTT long allele. Furthermore, the impulsive and irresponsible
      lifestyle features of psychopathy were higher among low-activity than high
      activity MAO-A carriers. These genetic effects were unexpectedly not moderated by
      a history of childhood abuse. Results provide evidence on the molecular genetics
      correlates of psychopathic traits in adulthood, relationships that should be
      investigated further in future research.

PMID- 22985018
TI  - Laparoscopic Tenckhoff catheter insertion: a retrospective study over 6 years.
AB  - INTRODUCTION: Peritoneal dialysis via Tenckhoff catheter predisposes to hernia
      formation due to both local and systemic factors. Another important complication
      of peritoneal catheter insertion includes infection, which can prompt removal of
      the catheter. METHODS: We performed a retrospective study between January 2005
      and July 2011 of 61 patients who underwent laparoscopic placement of a Tenckhoff
      catheter and peritoneal dialysis at our institution using a single-port
      technique. We analysed complications of Tenckhoff insertion, specifically
      infection and the formation of hernias requiring operative management. RESULTS:
      Infections noted in our patients included peritonitis (10%) and exit-site
      infection (5%). Of the five patients who required re-insertion of Tenckhoff
      catheter, four were for infective complications. A total of seven hernias
      developed in five (8%) of patients, mostly inguinal or umbilical near the Hassan
      port entry site. DISCUSSION: With infection and hernia formation being the main
      contributors to failure of the procedure, actively addressing the entry site and
      areas predisposed to hernia formation, observing aseptic technique and meticulous
      attention to early signs of complications during follow-up are vital to improve
      success rates. The outcomes of the laparoscopic single-port insertion technique
      shows promise compared with conventional Tenckhoff catheter insertion techniques.

PMID- 22985019
TI  - Efficient experimental design and analysis strategies for the detection of
      differential expression using RNA-Sequencing.
AB  - BACKGROUND: RNA sequencing (RNA-Seq) has emerged as a powerful approach for the
      detection of differential gene expression with both high-throughput and high
      resolution capabilities possible depending upon the experimental design chosen.
      Multiplex experimental designs are now readily available, these can be utilised
      to increase the numbers of samples or replicates profiled at the cost of
      decreased sequencing depth generated per sample. These strategies impact on the
      power of the approach to accurately identify differential expression. This study
      presents a detailed analysis of the power to detect differential expression in a
      range of scenarios including simulated null and differential expression
      distributions with varying numbers of biological or technical replicates,
      sequencing depths and analysis methods. RESULTS: Differential and non
      differential expression datasets were simulated using a combination of negative
      binomial and exponential distributions derived from real RNA-Seq data. These
      datasets were used to evaluate the performance of three commonly used
      differential expression analysis algorithms and to quantify the changes in power
      with respect to true and false positive rates when simulating variations in
      sequencing depth, biological replication and multiplex experimental design
      choices. CONCLUSIONS: This work quantitatively explores comparisons between
      contemporary analysis tools and experimental design choices for the detection of
      differential expression using RNA-Seq. We found that the DESeq algorithm performs
      more conservatively than edgeR and NBPSeq. With regard to testing of various
      experimental designs, this work strongly suggests that greater power is gained
      through the use of biological replicates relative to library (technical)
      replicates and sequencing depth. Strikingly, sequencing depth could be reduced as
      low as 15% without substantial impacts on false positive or true positive rates.

PMID- 22985020
TI  - Quantitative multianalyte microarray immunoassay utilizing upconverting phosphor
      technology.
AB  - A quantitative multianalyte immunoassay utilizing luminescent upconverting single
      crystal nanoparticles as reporters on an antibody array-in-well platform was
      demonstrated. Upconverting nanoparticles are inorganic rare earth doped materials
      that have the unique feature of converting low energy infrared radiation into
      higher energy visible light. Autofluorescence, commonly limiting the sensitivity
      of fluorescence-based assays, can be completely eliminated with photon
      upconversion technology because the phenomenon does not occur in biological
      materials. Biotinylated antibodies for three analytes (prostate specific antigen,
      thyroid stimulating hormone, and luteinizing hormone) were printed in an array
      format onto the bottom of streptavidin-coated microtiter wells. Analyte dilutions
      were added to the wells, and the analytes were detected with antibody-coated
      upconverting nanoparticles. Binding of the upconverting nanoparticles was imaged
      with an anti-Stokes photoluminescence microwell imager, and the standard curves
      for each analyte were quantified from the selected spot areas of the images.
      Single analyte and reference assays were also carried out to compare with the
      results of the multianalyte assay. Multiplexing did not have an effect on the
      assay performance. This study demonstrates the feasibility of upconverting single
      crystal nanoparticles for imaging-based detection of quantitative multianalyte
      assays.

PMID- 22985022
TI  - Growth of high-mobility Bi2Te2Se nanoplatelets on hBN sheets by van der Waals
      epitaxy.
AB  - The electrical detection of the surface states of topological insulators is
      strongly impeded by the interference of bulk conduction, which commonly arises
      due to pronounced doping associated with the formation of lattice defects. As
      exemplified by the topological insulator Bi(2)Te(2)Se, we show that via van der
      Waals epitaxial growth on thin hBN substrates the structural quality of such
      nanoplatelets can be substantially improved. The surface state carrier mobility
      of nanoplatelets on hBN is increased by a factor of about 3 compared to platelets
      on conventional Si/SiO(x) substrates, which enables the observation of well
      developed Shubnikov-de Haas oscillations. We furthermore demonstrate the
      possibility to effectively tune the Fermi level position in the films with the
      aid of a back gate.

PMID- 22985021
TI  - Association of geriatric conditions and cardiovascular diseases with disability
      in older adults with diabetes: findings from a nationally representative survey.
AB  - AIM: To examine how diabetes in combination with cardiovascular diseases
      (hypertension, heart disease and stroke) and geriatric conditions (cognitive
      impairment and depressive symptoms) affects the odds of disability in older
      adults. METHODS: We analyzed data from a nationally representative sample of
      people aged 65 years and over (n=2727) participating in the 2005 National Health
      Interview Survey in Taiwan. A total of 473 participants had a history of self
      reported physician diagnosed diabetes. Disability was defined as reporting
      limitations in one or more tasks of activities of daily living (ADL),
      instrumental activities of daily living (IADL) or general physical activities
      (GPA). The Mini-Mental State Examination was used to assess cognitive function.
      The Center for Epidemiologic Studies Depression Scale was used to assess
      depressive symptoms. RESULTS: After adjustment for other factors, cardiovascular
      diseases and geriatric conditions independently contributed to the excess odds of
      disability among participants with diabetes. Participants who had diabetes
      combined with cardiovascular diseases and geriatric conditions had odds ratios
      for ADL, IADL and GPA disability of 18.02 (95% CI 5.13-63.34), 7.95 (95% CI 4.07
      15.50) and 5.89 (95% CI 3.19-10.90), respectively. CONCLUSION: Our results
      highlight the high prevalence of co-occurrence of cardiovascular diseases with
      geriatric conditions in people with diabetes. Furthermore, the combined presence
      of these diseases and conditions is strongly associated with an excess odds of
      disability. These findings highlight the critical importance of preventing
      cardiovascular disease morbidity, and improving depressed mood and cognitive
      function in order to reduce disability risk in older adults with diabetes.

PMID- 22985023
TI  - pi-pi interaction assisted hydrodefluorination of perfluoroarenes by gold
      hydride: a case of synergistic effect on C-F bond activation.
AB  - "Synergistic effect" is prevalent in natural metalloenzymes in activating small
      molecules, and the success has inspired the development of artificial catalysts
      capable of unprecedented organic transformations. In this work, we found that the
      attractive pi-pi interaction between organic additives (as electron-donors) and
      the perfluorinated arenes (as electron acceptors) is effective in gold hydride
      catalyzed activation of C-F bonds, specifically hydrodefluorination (HDF) of
      perfluoroarenes catalyzed by the Sadighi's gold hydrides [(NHC)AuH] (NHC = N
      heterocyclic carbene). Although a weak interaction between [(NHC)AuH] and
      perfluoroarenes was observed from (1)H NMR and UV-vis spectroscopies, low
      reactivity of [(NHC)AuH] toward HDF was found. In contrast, in the presence of p
      N,N-dimethylaminopyridine (DMAP), the HDF of perfluoroarenes with silanes can be
      efficiently catalyzed by [(NHC)AuH], resulting in mainly the para
      hydrodefluorinated products with up to 90% yield and 9 turnovers. The yield of
      the reaction increases with the more electron-withdrawing groups and degree of
      fluorination on the arenes, and the HDF reaction also tolerates different
      function groups (such as formyl, alkynyl, ketone, ester, and carboxylate groups),
      without reduction or hydrogenation of these function groups. To reveal the role
      of DMAP in the reactions, the possible pi-pi interaction between DMAP and
      perfluoroarenes was suggested by UV-vis spectral titrations, (1)H NMR
      spectroscopic studies, and DFT calculations. Moreover, (1)H and (19)F-NMR studies
      show that this pi-pi interaction promotes hydrogen transfer from [(NHC)AuH] to
      pyridyl N atom, resulting in C-F bond cleavage. The interpretation of pi-pi
      interaction assisted C-F activation is supported by the reduced activation
      barriers in the presence of DMAP (31.6 kcal/mol) than that in the absence of DMAP
      (40.8 kcal/mol) for this reaction. An analysis of the charge distribution and
      transition state geometries indicate that this HDF process is controlled by the
      pi-pi interaction between DMAP and perfluoroarenes, accompanied with the changes
      of partial atomic charges.

PMID- 22985024
TI  - Myocardial protection against ischemia-reperfusion injury by GLP-1: molecular
      mechanisms.

PMID- 22985025
TI  - Association between MMP-2 and TIMP-2 gene polymorphisms and advanced-stage
      endometriosis in Korean women.
AB  - PROBLEM: To characterize the genetic variation across the MMP-2 and TIMP-2 gene
      with the risk of advanced-stage endometriosis. METHOD OF STUDY: Ten single
      nucleotide polymorphisms (SNPs) and haplotype associations between MMP-2
      (9082A>G, 9152A>G, 105330C>T, 14931T>C, 15918T>C, 18796G>A, 19033G>A, 19218A>G,
      25190A>G, and 28542C>T) and TMIP-2 gene (42138327C>T, 42141169G>A, 42144611A>G,
      42152781C>T, 42155855G>A, 42175617C>T, 42181597G>A, 42183387T>C, 42196041G>C, and
      42196430T>C) were examined in 201 patients and 183 controls. RESULTS: In MMP-2,
      G/A haplotype of 9082A>G and 9152A>G in intron 2 was associated with a reduced
      risk of endometriosis (OR 0.7, 95% CI 0.5-1.0, P = 0.04). In TIMP-2, the CC
      genotype of 42196430T>C and C/C haplotype of 42196041G>C/42196430T>C in the
      promoter region showed an increased risk of endometriosis (OR 3.0, 95% CI 1.2
      8.0, P = 0.02; OR 1.6, 95% CI 1.1-2.4, P = 0.02), and the CC genotype of
      42183387T>C and the C/G/C haplotype of 42175617C>T/42181597G>A/42183387T>C in
      intron 1 were associated with a reduced risk (OR 0.5, 95% CI 0.3-0.97, P = 0.04;
      OR 0.6, 95% CI 0.4-0.95, P = 0.03). CONCLUSION: The MMP-2 and TIMP-2
      polymorphisms are associated with advanced-stage endometriosis. Especially, the
      risk of endometriosis was different according to the genetic position in the TIMP
      2 gene.

PMID- 22985026
TI  - Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28
      triggered proximal biochemical events, leading to T-cell unresponsiveness in
      mycobacterial diseases.
AB  - BACKGROUND: Advanced stages of leprosy show T cell unresponsiveness and lipids of
      mycobacterial origin are speculated to modulate immune responses in these
      patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and
      Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated
      signalling. RESULTS: We observed that lipid antigens significantly inhibit
      proximal early signalling events like Zap-70 phosphorylation and calcium
      mobilization. Interestingly, these antigens preferentially curtailed TCR
      triggered early downstream signalling events like p38 phosphorylation whereas
      potentiated that of Erk1/2. Further, at later stages inhibition of NFAT binding,
      IL-2 message, CD25 expression and T-cell blastogenesis by PGL-1 and Man-LAM was
      noted. CONCLUSION: Altogether, we report that Man-LAM and PGL-1 preferentially
      interfere with TCR/CD28-triggered upstream cell signalling events, leading to
      reduced IL-2 secretion and T-cell blastogenesis which potentially could lead to
      immunosupression and thus, disease exacerbation, as noted in disease spectrum.

PMID- 22985028
TI  - Familial episodic ataxia in lambs.
AB  - HISTORY: A similar episodic neurological disorder occurred in new born lambs on
      two unrelated properties involving disparate breeds of sheep. Because of the
      number of lambs born, cross-breeding and the fact it occurred in some mating
      groups and not others, a dominant mode of inheritance was, initially and
      separately, suspected in each case. The sires of affected lambs were apparently
      normal. Whereas one was New Zealand Romney, the other was a composite breed with
      East Friesian genetics, but both rams originated from the same source property.
      To investigate the pathogenesis of the disorder these two rams were acquired and
      mated with unrelated sheep, under experimental conditions in a more controlled
      environment. CLINICAL FINDINGS: A proportion of lambs born to both sires
      exhibited a similar neurological disorder. Some lambs were noted to be abnormal
      at birth, both on home properties and in the experimental flock. They tended to
      adopt a head and neck extended posture and were slow to get to their feet and
      suckle when they then became more or less normal. When forced to move, they and
      other more robust lambs elicited an asymmetric gait, base-wide extensor
      hypertonia (hypometria) of thoracic limbs and flexor hypertonia (hypermetria) of
      pelvic limbs. In some there was nystagmus. After several metres of asymmetric
      ataxic gait they would fall to one side, sometimes adopting a sitting position.
      Recovery usually occurred in one to several minutes. As lambs aged, it became
      more difficult to elicit the episodes of dysfunction and by 6 months of age they
      appeared normal. DIAGNOSIS: The disorder was diagnosed as a dominant familial
      episodic cerebellovestibular ataxia inherited as a dominant trait, with
      incomplete penetration of observed clinical signs and variable expressivity.
      CLINICAL RELEVANCE: A proportion of affected lambs are likely to die in the
      neonatal period so the specific nature of the disorder may go unrecognised.
      Because of incomplete penetrance and varying expressivity, many of the lambs
      carrying this mutation will survive without showing clinical signs and may enter
      breeding flocks, where the disorder may be perpetuated and contribute to neonatal
      deaths.

PMID- 22985027
TI  - Guaianolide sesquiterpene lactones, a source to discover agents that selectively
      inhibit acute myelogenous leukemia stem and progenitor cells.
AB  - Small molecules that can selectively target cancer stem cells (CSCs) remain rare
      currently and exhibit no common structural features. Here we report a series of
      guaianolide sesquiterpene lactones (GSLs) and their derivatives that can
      selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells.
      Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide
      (MCL), are able to reduce the proportion of AML stem cells (CD34+CD38-) in
      primary AML cells. Targeting of AML stem cells is further confirmed by a sharp
      reduction of colony-forming units of primary AML cells upon MCL treatment.
      Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in
      plasma and in vivo and demonstrates remarkable therapeutic efficacy in the
      nonobese diabetic/severe combined immunodeficiency AML models. These findings
      indicate that GSL is an ample source for chemical agents against AML stem or
      progenitor cells and that GSL is potentially highly useful to explore anti-CSC
      approaches.

PMID- 22985029
TI  - Introducing the Best of the AcademyHealth Annual Research Meeting.

PMID- 22985031
TI  - Reporting of quality indicators and improvement in hospital performance: the
      P.Re.Val.E. Regional Outcome Evaluation Program.
AB  - OBJECTIVE: To evaluate whether reporting of hospital performance was associated
      with a change in quality indicators in Italian hospitals. DATA SOURCES/STUDY
      SETTING: Nationwide Hospital Information System for 2006-2009. STUDY DESIGN: We
      performed a pre-post evaluation in Lazio (before and after disclosure of the
      Regional Outcome Evaluation Program P.Re.Val.E.) and a comparative evaluation
      versus Italian regions without comparable programs. We analyzed risk-adjusted
      proportions of percutaneous coronary intervention (PCI), hip fractures operated
      on within 48 hours, and cesarean deliveries. DATA COLLECTION/EXTRACTION METHODS:
      Using standardized ICD-9-CM coding algorithms, we selected 381,053 acute
      myocardial infarction patients, 250,712 hip fractures, and 1,736,970 women who
      had given birth. PRINCIPAL FINDINGS: In Lazio PCI within 48 hours changed from
      22.49 to 29.43 percent following reporting of the P.Re.Val.E results (relative
      increase, 31 percent; p < .001). In the other regions this proportion increased
      from 22.48 to 27.09 percent during the same time period (relative increase, 21
      percent; p < .001). Hip fractures operated on within 48 hours increased from
      11.73 to 15.78 percent (relative increase, 34 percent; p < .001) in Lazio, and
      not in other regions (29.36 to 28.57 percent). Cesarean deliveries did not
      decrease in Lazio (34.57-35.30 percent), and only slightly decreased in the other
      regions (30.49-28.11 percent). CONCLUSIONS: Reporting of performance data may
      have a positive but limited impact on quality improvement. The evaluation of
      quality indicators remains paramount for public accountability.

PMID- 22985030
TI  - Composite measures for rating hospital quality with major surgery.
AB  - OBJECTIVE: To assess the value of a novel composite measure for identifying the
      best hospitals for major procedures. DATA SOURCE: We used national Medicare data
      for patients undergoing five high-risk surgical procedures between 2005 and 2008.
      STUDY DESIGN: For each procedure, we used empirical Bayes techniques to create a
      composite measure combining hospital volume, risk-adjusted mortality with the
      procedure of interest, risk-adjusted mortality with other related procedures, and
      other variables. Hospitals were ranked based on 2005-2006 data and placed in one
      of three groups: 1-star (bottom 20 percent), 2-star (middle 60 percent), and 3
      star (top 20 percent). We assessed how well these ratings forecasted risk
      adjusted mortality rates in the next 2 years (2007-2008), compared to other
      measures. PRINCIPAL FINDINGS: For all five procedures, the composite measures
      based on 2005-2006 data performed well in predicting future hospital performance.
      Compared to 1-star hospitals, risk-adjusted mortality was much lower at 3-star
      hospitals for esophagectomy (6.7 versus 14.4 percent), pancreatectomy (4.7 versus
      9.2 percent), coronary artery bypass surgery (2.6 versus 5.0 percent), aortic
      valve replacement (4.5 versus 8.5 percent), and percutaneous coronary
      interventions (2.4 versus 4.1 percent). Compared to individual surgical quality
      measures, the composite measures were better at forecasting future risk-adjusted
      mortality. These measures also outperformed the Center for Medicare and Medicaid
      Services (CMS) Hospital Compare ratings. CONCLUSION: Composite measures of
      surgical quality are very effective at predicting hospital mortality rates with
      major procedures. Such measures would be more informative than existing quality
      indicators in helping patients and payers identify high-quality hospitals with
      specific procedures.

PMID- 22985032
TI  - Care coordination for the chronically ill: understanding the patient's
      perspective.
AB  - OBJECTIVE: To identify factors associated with perception of care coordination
      problems among chronically ill patients. METHODS: Patient-level data were
      obtained from a random-digit dial telephone survey of adults with chronic
      conditions. The survey measured respondents' self-report of care coordination
      problems and level of patient activation, using the Patient Activation Measure
      (PAM-13). Logistic regression was used to assess association between respondents'
      self-report of care coordination problems and a set of patient characteristics.
      RESULTS: Respondents in the highest activation stage had roughly 30-40 percent
      lower odds of reporting care coordination problems compared to those in the
      lowest stage (p < .01). Respondents with multiple chronic conditions were
      significantly more likely to report coordination problems than those with
      hypertension only. Respondents' race/ethnicity, employment, insurance status,
      income, and length of illness were not significantly associated with self
      reported care coordination problems. CONCLUSION: We conclude that patient
      activation and complexity of chronic illness are strongly associated with
      patients' self-report of care coordination problems. Developing targeted
      strategies to improve care coordination around these patient characteristics may
      be an effective way to address the issue.

PMID- 22985034
TI  - Delays in seeking conventional medical care and complementary and alternative
      medicine utilization.
AB  - OBJECTIVE: To test the association between delays in utilization of conventional
      medical care and complementary and alternative medicine (CAM) utilization. DATA
      SOURCE: The 2007 National Health Interview Survey, a cross-sectional nationally
      representative study of adults aged 18 years and older. STUDY DESIGN: Using zero
      inflated regression models, delays in utilizing conventional care due to
      organizational inaccessibility are examined to determine whether delays are
      associated with both the decision to try CAM and the number of CAM types used.
      PRINCIPAL FINDINGS: Individuals have significantly higher odds using provider
      based CAM types if they delayed seeking conventional care due to organizational
      inaccessibility (OR = 1.63). Individuals use significantly more types of both
      provider-based (IRR = 1.35) and non-provider-based (IRR = 1.49) CAM if they
      delayed seeking conventional care due to organizational inaccessibility.
      CONCLUSION: Individuals who delay seeking conventional medical care are more
      likely to use CAM and use more types of CAM. The current structure of the
      conventional health care system may have created barriers that can make
      conventional health care inaccessible. Individuals who face these barriers appear
      to be pushed not only into trying CAM but using a greater number of CAM types, a
      finding not in previous research.

PMID- 22985036
TI  - Venous ulcer treatment guidelines: revisited but not yet changed.

PMID- 22985033
TI  - Hospital-level variation in the use of intensive care.
AB  - OBJECTIVE: To determine the extent to which hospitals vary in the use of
      intensive care, and the proportion of variation attributable to differences in
      hospital practice that is independent of known patient and hospital factors. DATA
      SOURCE: Hospital discharge data in the State Inpatient Database for Maryland and
      Washington States in 2006. STUDY DESIGN: Cross-sectional analysis of 90 short
      term, acute care hospitals with critical care capabilities. DATA
      COLLECTION/METHODS: We quantified the proportion of variation in intensive care
      use attributable to hospitals using intraclass correlation coefficients derived
      from mixed-effects logistic regression models after successive adjustment for
      known patient and hospital factors. PRINCIPAL FINDINGS: The proportion of
      hospitalized patients admitted to an intensive care unit (ICU) across hospitals
      ranged from 3 to 55 percent (median 12 percent; IQR: 9, 17 percent). After
      adjustment for patient factors, 19.7 percent (95 percent CI: 15.1, 24.4) of total
      variation in ICU use across hospitals was attributable to hospitals. When
      observed hospital characteristics were added, the proportion of total variation
      in intensive care use attributable to unmeasured hospital factors decreased by 26
      14.6 percent (95 percent CI: 11, 18.3 percent). CONCLUSIONS: Wide variability
      exists in the use of intensive care across hospitals, not attributable to known
      patient or hospital factors, and may be a target to improve efficiency and
      quality of critical care.

PMID- 22985037
TI  - A review of the scientific evidence for biofilms in wounds.
AB  - Both chronic and acute dermal wounds are susceptible to infection due to sterile
      loss of the innate barrier function of the skin and dermal appendages,
      facilitating the development of microbial communities, referred to as biofilms,
      within the wound environment. Microbial biofilms are implicated in both the
      infection of wounds and failure of those wounds to heal. The aim of this review
      is to provide a summary of published papers detailing biofilms in wounds, the
      effect they have on infection and wound healing, and detailing methods employed
      for their detection. The studies highlighted within this paper provide evidence
      that biofilms reside within the chronic wound and represent an important
      mechanism underlying the observed, delayed healing and infection. The reasons for
      this include both protease activity and immunological suppression. Furthermore, a
      lack of responsiveness to an array of antimicrobial agents has been due to the
      biofilms' ability to inherently resist antimicrobial agents. It is imperative
      that effective strategies are developed, tested prospectively, and employed in
      chronic wounds to support the healing process and to reduce infection rates. It
      is increasingly apparent that adoption of a biofilm-based management approach to
      wound care, utilizing the "antibiofilm tool box" of therapies, to kill and
      prevent reattachment of microorganisms in the biofilm is producing the most
      positive clinical outcomes and prevention of infection.

PMID- 22985038
TI  - The influence of selected demographic factors and wound location on the
      concentration of vascular endothelial growth factor (VEGF-A) in the wound healing
      process after neurosurgery: brief report.
AB  - The main aim of the work was to estimate the influence of selected demographic
      factors and wound location on the concentration of the vascular endothelial
      growth factor (VEGF-A) in patients after neurosurgical operations. The study
      included 20 adult patients who received a surgical treatment because of
      degenerative spine changes. Measurements of the concentration of the VEGF-A in
      the patients' blood serum were taken three times (the first time--before the
      operation; the second time--during the first 24 hours after surgery; and the
      third time--between the fifth and the seventh day after the operation). No
      statistically significant correlation between the concentration of VEGF-A in the
      patients' blood serum before and after the operation was noted. A statistically
      significant correlation between the concentration of VEGF-A in the individual
      measurements was found. It can be concluded that people with a higher
      concentration of VEGF-A before surgery obtained a higher concentration of VEGF-A
      in the measurements taken after the operation. There is a statistically
      significant link between the patient's age and the concentration of VEGF-A during
      the immediate postoperative period (the older the patient, the higher the level
      of VEGF-A is observed).

PMID- 22985039
TI  - Outcome after burns: an observational study on burn scar maturation and
      predictors for severe scarring.
AB  - Long-term outcome of burn scars as well as the relation with clinically relevant
      parameters has not been studied quantitatively. Therefore, we conducted a
      detailed analysis on the clinical changes of burn scars in a longitudinal setup.
      In addition, we focused on the differences in scar quality in relation to the
      depth, etiology of the burn wound and age of the patient. Burn scars of 474
      patients were subjected to a scar assessment protocol 3, 6, and 12 months
      postburn. Three different age groups were defined (<=5, 5-18, and >=18 years).
      The observer part of the patient and observer scar assessment scale revealed a
      significant (p < 0.001) improvement in scar quality at 12 months compared with
      the 3- and 6-month data. Predictors for severe scarring are depth of the wound (p
      < 0.001) and total body surface area burned (p < 0.001). Etiology (p = 0.753) and
      age (p > 0.230) have no significant influence on scar quality when corrected for
      sex, total body surface area burned, time, and age or etiology, respectively.

PMID- 22985040
TI  - Notch signaling pathway in keloid disease: enhanced fibroblast activity in a
      Jagged-1 peptide-dependent manner in lesional vs. extralesional fibroblasts.
AB  - Keloid disease (KD) is a fibroproliferative disorder of unknown etiopathogenesis
      with ill-defined treatment. There is increasing evidence to suggest that aberrant
      Notch signaling may contribute directly to skin pathogenesis and altered
      expression of Notch receptors identified in KD. Therefore, the aim of this study
      was to investigate the Notch signaling pathway in KD compared to normal skin
      (NS). In this study, we employed in vitro primary cell culture models to
      elucidate the role of Notch signaling in 44 tissue samples from patients with KD
      split into keloid and extralesional (EL) samples (internal control) from the same
      patients, and six NS tissue samples (external control). We show the presence of a
      significant (p < 0.05) up-regulation of Notch receptors and ligand Jagged-1 (JAG
      1) in KD compared to EL and NS tissue samples. Cell spreading, attachment, and
      proliferation were significantly (p < 0.05) reduced in JAG-1 antisense-treated
      primary dermal fibroblasts isolated from KD and treated with gamma-secretase
      inhibitor (blocks proteolytic cleavage and activation of Notch), evaluated by
      real-time cell analyzer (RTCA) on a microelectronic sensory array. In contrast,
      extralesional skin fibroblasts (ELF) treated with recombinant human JAG-1 (rh-JAG
      1) peptide showed significant (p < 0.05) enhancement of cell spreading,
      attachment, and proliferation in RTCA. Activation/inhibition of JAG-1 and Notch
      signaling significantly (p < 0.05) altered the behavior of primary keloid
      fibroblasts and ELF, in cell migration (using a scratch wound assay), invasion
      (using a 3D invasion assay), and angiogenesis (in vitro coculture tube formation
      assay). In conclusion, this is the first study to demonstrate a potential role
      for the Notch signaling pathway in KD progression and that targeting this pathway
      may provide a novel strategy for treatment of KD.

PMID- 22985041
TI  - Exogenous calreticulin improves diabetic wound healing.
AB  - A serious consequence of diabetes mellitus is impaired wound healing, which
      largely resists treatment. We previously reported that topical application of
      calreticulin (CRT), an endoplasmic reticulum chaperone protein, markedly enhanced
      the rate and quality of wound healing in an experimental porcine model of
      cutaneous repair. Consistent with these in vivo effects, in vitro CRT induced the
      migration and proliferation of normal human cells critical to the wound healing
      process. These functions are particularly deficient in poor healing diabetic
      wounds. Using a genetically engineered diabetic mouse (db/db) in a full-thickness
      excisional wound healing model, we now show that topical application of CRT
      induces a statistically significant decrease in the time to complete wound
      closure compared with untreated wounds by 5.6 days (17.6 vs. 23.2). Quantitative
      analysis of the wounds shows that CRT increases the rate of reepithelialization
      at days 7 and 10 and increases the amount of granulation tissue at day 7
      persisting to day 14. Furthermore, CRT treatment induces the regrowth of
      pigmented hair follicles observed on day 28. In vitro, fibroblasts isolated from
      diabetic compared with wild-type mouse skin and human fibroblasts cultured under
      hyperglycemic compared with normal glucose conditions proliferate and strongly
      migrate in response to CRT compared with untreated controls. The in vitro effects
      of CRT on these functions are consistent with CRT's potent effects on wound
      healing in the diabetic mouse. These studies implicate CRT as a potential
      powerful topical therapeutic agent for the treatment of diabetic and other
      chronic wounds.

PMID- 22985044
TI  - Implementation of the solvent macromolecule boundary potential and application to
      model and realistic enzyme systems.
AB  - The implementation of the solvent macromolecule boundary potential (SMBP) by
      Benighaus and Thiel (J. Chem. Theory Comput. 2009, 5, 3114) into the program
      package CHARMM is presented. The SMBP allows for the efficient calculation of
      solvent effects for large macromolecules using irregularly shaped dielectric
      boundaries. In contrast to the generalized solvent boundary potential (GSBP) by
      Roux et al. (J. Chem. Phys. 2001, 114, 2924) from which it is derived, the SMBP
      is targeted for quantum mechanical/molecular mechanical (QM/MM) setups using ab
      initio methods for the QM part. After presenting benchmark results for simple
      model systems, applications of the SMBP for the calculation of geometries,
      reaction energy barriers, and vibrational frequencies for an alkaline phosphatase
      (AP) enzyme are discussed. Although the effect of the boundary potential on
      optimized structures (including the transition state) and vibrational frequencies
      is relatively small, the energetics of the phosphoryl transfer catalyzed by AP
      depend significantly on the boundary potential. Finally, to emphasize a unique
      feature of our implementation, we apply both SMBP and GSBP to the calculation of
      the energy barrier for a proton transfer reaction in a simple model channel,
      where the effect of an external transmembrane potential is studied. Due to the
      dipolar response of the polar environment, the effective charge displacement
      estimated based on the effect of the membrane potential on the proton transfer
      energetics deviates from the net charge that passes the membrane.

PMID- 22985042
TI  - Identification of biomarkers in sequential biopsies of patients with chronic
      wounds receiving simultaneous acute wounds: a genetic, histological, and
      noninvasive imaging study.
AB  - Chronic wounds are common and lead to significant patient morbidity. A better
      understanding of their pathogenesis and relevant biomarkers are required. We
      compared acute and chronic wounds in the same individual using noninvasive
      imaging including spectrophotometric intracutaneous analysis (SIAscopy) and full
      field laser perfusion imaging. Gene expression analysis was also performed on
      sequential biopsies. Whole genome gene expression microarray analysis (44k),
      quantitative polymerase chain reaction, and immunohistochemistry were carried out
      to determine gene expression levels in tissue biopsies. Fifteen Caucasian
      patients with chronic venous ulcers had biopsies of the wound edges and
      simultaneously had an acute wound created on their upper arm on days 0, 7, and
      14. SIAscopy revealed increased levels of melanin (p < 0.001), reduced levels of
      collagen (p < 0.001), and hemoglobin (p = 0.022) in chronic wounds. Microarray
      and subsequent quantitative polymerase chain reaction analysis confirmed an
      overall differential expression in acute and chronic wounds for several genes.
      Significantly higher levels of inhibin, beta A (INHBA) expression were confirmed
      in the dermis of chronic wounds (p < 0.05). Additionally, INHBA and
      thrombospondin 1 messenger RNA levels significantly correlated with SIAscopy
      measurements (p < 0.05). This unique study has showed aberrant expression of
      INHBA in chronic wounds using a sequential biopsy model of chronic vs. acute
      wounds in the same individual.

PMID- 22985045
TI  - Cauda equina syndrome secondary to intradural renal cell carcinoma metastasis
      haemorrhage.
AB  - Intradural renal cell carcinoma (RCC) metastasis is rare. We report a case of an
      81-year-old female presenting with acute cauda equina syndrome (CES), secondary
      to intradural RCC metastasis haemorrhage. To our knowledge this is the first case
      of CES secondary to acute haemorrhage within an intradural RCC metastasis.

PMID- 22985047
TI  - Age-related impairment of visual recognition memory correlates with impaired
      synaptic distribution of GluA2 and protein kinase Mzeta in the dentate gyrus.
AB  - Age-related functional alterations in the perforant path projection from the
      entorhinal cortex to the dentate gyrus (DG) of the hippocampus play a major role
      in age-related memory impairments, but little is known about the molecular
      mechanisms responsible for these changes. In a recent study, young and aged
      monkeys were tested on the visual recognition memory test "delayed nonmatching-to
      sample"; then, electron microscopic immunocytochemistry was performed in the
      hippocampal DG to determine the subcellular localization of the GluA2 subunit of
      the glutamate alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid receptor
      (AMPAR) and protein kinase Mzeta (PKMzeta), which promotes memory storage by
      regulating GluA2-containing AMPAR trafficking. The results obtained suggest that
      age-related deficits in visual recognition memory are coupled with impairment in
      PKMzeta-dependent maintenance of GluA2 at the synapse. Together with previous
      evidences of the critical role of PKMzeta in memory consolidation, these data
      render this enzyme an attractive potential therapeutic target for treating age
      related memory decline, and support the view that the pharmacological
      manipulation of AMPAR trafficking in the synapses may provide new insights in the
      search of memory enhancers for aged individuals, including those affected by
      Alzheimer disease.

PMID- 22985049
TI  - Excited state tautomerization of 7-azaindole in a 1:1 complex with delta
      valerolactam: a comparative study with the homodimer.
AB  - A comparative analysis for relative stability between normal and tautomeric forms
      in the excited electronic states of 7-azaindole...delta-valerolactam 1:1 complex
      and 7-azaindole homodimer has been presented. The tautomeric configuration of the
      complex is estimated to be ~6 kcal/mol more stable than normal form, and the same
      for homodimer appears to be ~10 kcal/mol. Consistent with these estimates both
      the complex and homodimer undergo facile double proton transfer tautomerization
      upon UV excitation in hydrocarbon solutions (Chou; et al. J. Am. Chem. Soc. 1995,
      117, 7259). However, we notice that such similarity in photophysical behavior of
      the two hydrogen-bonded systems is lost completely in a cold supersonic jet
      expansion. The jet-cooled homodimer emits only the tautomer fluorescence in the
      visible spectral region, but the complex emits exclusively from the locally
      excited state in ultraviolet. We have interpreted this contrast by arguing that
      the effective barrier for excited state double proton exchange tautomerization of
      the complex is larger compared to that of the homodimer, and the difference
      originates because of asymmetric nature of the two hydrogen bonds of the complex.

PMID- 22985048
TI  - Association of pre-transplant statin use with delayed graft function in kidney
      transplant recipients.
AB  - BACKGROUND: Administration of HMG-CoA reductase inhibitors (statins), prior to
      ischemia or prior to reperfusion has been shown to decrease ischemia-reperfusion
      renal injury in animal studies. It is unknown whether this protective effect is
      applicable to renal transplantation in humans. The aim of this study was to
      determine the relationship between prior statin use in renal transplant
      recipients and the subsequent risk of delayed graft function. METHODS: All
      patients who underwent deceased or living donor renal transplantation at the
      Princess Alexandra Hospital between 1 July 2008 and 1 August 2010 were included
      in this retrospective, observational cohort study. Graft function was classified
      as immediate graft function (IGF), dialysis-requiring (D-DGF) and non-dialysis
      requiring (ND-DGF) delayed graft function. The independent predictors of graft
      function were evaluated by multivariable logistic regression, adjusting for donor
      characteristics, recipient characteristics, HLA mismatch and ischaemic times.
      RESULTS: Overall, of the 266 renal transplant recipients, 21% exhibited D-DGF,
      39% had ND-DGF and 40% had IGF. Statin use prior to renal transplantation was not
      significantly associated with the risk of D-DGF (adjusted odds ratio [OR] 1.05,
      95% CI 0.96 - 1.15, P = 0.28). This finding was not altered when D-DGF and ND-DGF
      were pooled together (OR 0.98; 95% CI 0.89-1.06, p = 0.56). CONCLUSIONS: The
      present study did not show a significant, independent association between prior
      statin use in kidney transplant recipients and the occurrence of delayed graft
      function.

PMID- 22985050
TI  - Anti-viral and anti-bacterial activities of an extract of blackcurrants (Ribes
      nigrum L.).
AB  - The inhibitory effects of an extract of the blackcurrant (Ribes nigrum L.)
      against pathogens associated with oral, nasopharyngeal and upper respiratory
      infectious diseases; namely respiratory syncytial virus (RSV), influenza virus A
      and B (IFV-A and IFV-B), adenovirus (AdV), herpes simplex virus type 1,
      Haemophilus influenzae type B, Streptococcus pneumoniae and Streptococcus mutans,
      were investigated. Less than 1% concentration of extract of blackcurrant
      inhibited replication of RSV, IFV-A and -B and HSV-1 by over 50% and a 10%
      extract inhibited adsorption of these viruses onto the cell surface by over 95%.
      The effects on AdV were much less pronounced; the half minimal inhibitory
      concentration of AdV replication was 2.54 +/- 0.26, and a 10% concentration of
      the extract inhibited AdV adsorption on the cell surface by 72.9 +/- 3.4%. The
      antibacterial activities of the blackcurrant were evaluated based on its efficacy
      as a disinfectant. A 10% extract disinfected 99.8% of H. Influenzae type B and
      78.9% of S. pneumoniae in 10 min, but had no demonstrable effect against S.
      mutans. The blackcurrant extract still showed antiviral and antibacterial
      activities after the pH had been made neutral with sodium hydroxide, suggesting
      that these activities are not the result of acidic reactions or of components
      precipitated at a neutral pH. These findings demonstrate the potential of
      blackcurrant extract as a functional food for oral care.

PMID- 22985051
TI  - Ecotope effect in Triatoma brasiliensis (Hemiptera: Reduviidae) suggests
      phenotypic plasticity rather than adaptation.
AB  - Triatoma brasiliensis (Hemiptera: Reduviidae) is an important vector of Chagas'
      disease in both sylvatic and peridomestic ecotopes. Discriminating between these
      populations of Triatominae has been proposed as a means of investigating re
      infestation rates of human dwellings. Geometric morphometrics have been widely
      applied in the study of Triatominae polymorphisms at species and population
      levels. This study characterizes morphometric differences between sylvatic and
      peridomestic populations, as well as between sexes in T. brasiliensis specimens
      from Jaguaruana, Ceara, in northeastern Brazil. No differences in either the
      shape or size of the cephalic capsule were apparent between sexes or ecotopes.
      However, the wings showed differentiation in shape and size. Sexual dimorphism
      was detected, with females presenting significantly higher values and
      conformations. Size differentiation was also evident, with sylvatic specimens
      being generally larger than peridomestic examples. These results indicate that
      differences in the wings of T. brasiliensis may be related to the existence of
      phenotypic plasticity, and variations in size and shape may be associated with
      different ecotopes, possibly as a result of conditions in each micro-habitat,
      such as temperature, relative humidity, food supply and density. 

PMID- 22985053
TI  - Pros and cons: prospective predictors of marijuana use on a college campus.
AB  - Marijuana use on college campuses is prevalent and associated with high rates of
      abuse and dependence. The Marijuana Decisional Balance (MDB) scales measure
      perceived pros and cons toward marijuana use. Evidence supports reliability and
      concurrent validity of these scales, but the predictive validity has not yet been
      assessed. The current study evaluated the prospective predictive validity of pros
      and cons scales for marijuana use, as well as explored predictive validity for
      marijuana problem indicators. Secondary analyses included test-retest reliability
      and internal consistency, to provide additional evidence of psychometric
      properties. A total of 149 college students (57% recent marijuana users, 77%
      lifetime users) participated in a baseline survey, then completed a second survey
      one month later. All provided data on marijuana pros and cons, as well as use
      status in the past month. Users at each time point reported on use frequency,
      problems, and disorder symptoms. In the month between assessments, 55% of the
      students used marijuana. Both pros and cons subscales prospectively predicted use
      status in the subsequent month, but not use frequency. Pros prospectively
      predicted marijuana problems and dependence symptoms at follow-up, and remained a
      significant predictor of later dependence symptoms even after controlling for
      baseline dependence symptoms. In contrast, pros only marginally predicted abuse.
      Cons did not predict problems, abuse, or dependence symptoms. Pros and cons
      showed strong test-retest reliability (rs = 0.80-0.85) and internal consistency
      (alphas = 0.92-0.95). In a college sample, pros and cons of marijuana use
      demonstrated stability over one month, and prospectively predicted use. Pros may
      also have utility in predicting problems and dependence potential on college
      campuses.

PMID- 22985052
TI  - Quantitative measurement of blaCMY-2 in a longitudinal observational study of
      dairy cattle treated with ceftiofur.
AB  - There is concern that a relationship exists between antibiotic use in livestock
      production and the emergence, spread, and persistence of antibiotic resistance.
      It is important to understand the impact that therapeutic doses of antibiotics
      for treatment of disease have on resistance because disease treatment typically
      involves higher doses of antibiotic over short time spans. Absolute quantities of
      the antibiotic resistance gene bla(CMY-2) were measured by real-time quantitative
      polymerase chain reaction (qPCR) in the bacterial community DNA of fecal samples
      from dairy cattle that were given a 5-day course of ceftiofur and untreated
      cattle during a longitudinal, observational study. A hierarchical linear model
      that accounts for left-censored data and repeated measures was used to estimate
      group means of bla(CMY-2) from the qPCR data. Ceftiofur-treated animals had
      significantly higher mean quantities of bla(CMY-2) than untreated animals during
      treatment. On the first day post-treatment, mean quantities of bla(CMY-2)
      returned to pre-treatment levels and remained low in both groups for the
      remainder of the study. The use of qPCR to measure bla(CMY-2) quantities provided
      evidence that the burden of resistance in treated animals may have increased
      temporarily, a result that was not evident when using only cultivation-based
      methods of testing for resistance.

PMID- 22985054
TI  - The way one thinks affects the way one drinks: subjective evaluations of alcohol
      consequences predict subsequent change in drinking behavior.
AB  - Heavy alcohol use and related consequences are common during the college years
      and are associated with deleterious outcomes for both the students themselves and
      the college community. Some college students make self-initiated changes to their
      drinking to avoid such outcomes, but little is known about how such adjustments
      occur, or characteristics that are associated with making these adjustments.
      Based on Social Learning Theory (SLT), one cognitive factor that may predict
      within-person changes in drinking is the subjective evaluations of alcohol
      consequences (i.e., the extent to which consequences are perceived as negative,
      aversive, or severe). The aim of the present study was to investigate whether
      subjective evaluations of recently experienced consequences influence within
      person changes in drinking behavior. In 10 weekly, web-based surveys, regularly
      drinking college students (N = 96, 50 female) reported on their previous week
      alcohol use and experience of 24 alcohol-related consequences, as well as their
      subjective evaluations of those consequences. Results demonstrated that
      evaluations across the consequences varied, and that in addition to differing
      from one another, students' evaluations of consequences differed at the within
      person level over time. Most important, hierarchical linear model tests revealed
      that students drank less and experienced fewer consequences following weeks in
      which they rated their consequences as more negative (relative to their own
      typical subjective evaluations), suggesting that viewing one's recent
      consequences as aversive prompts self-initiated behavior change. Findings of the
      present study have potential to inform interventions for college drinking,
      particularly those that target how individuals think about their behavior and its
      consequences.

PMID- 22985055
TI  - Patterns of use and motivations for consuming alcohol mixed with energy drinks.
AB  - Use of alcohol mixed with energy drinks (AmED) is an increasingly prevalent
      trend. However, recent research has suggested that AmED use may result in
      increased alcohol consumption and engagement in risk behavior postingestion.
      Although the majority of research has been focused on AmED use outcomes, there is
      a current paucity of data on the patterns of AmED use and motives for
      consumption. Four hundred and three participants from an Australian community
      sample (n = 244 women) ages 18-35 who had consumed alcohol mixed simultaneously
      with energy drinks (ED) in the preceding 6 months completed an online survey
      regarding use of EDs, alcohol, and AmED. Although AmED sessions occurred
      relatively infrequently compared to alcohol sessions, the alcohol and ED quantity
      consumed in AmED sessions was significantly greater than recommended intake.
      Reports of AmED use context indicated that participants typically consumed AmED
      while engaging in heavy drinking in public venues. However, the primary motives
      for AmED use related to the situational context of use, functional and hedonistic
      outcomes, as well as the pleasurable taste; few participants reported using AmED
      to increase alcohol intake, to mask intoxication, to hide alcohol's flavor, or to
      simulate an illicit drug "high." AmED users may be coingesting in a context and
      at a quantity that enhances the possibility of risky alcohol outcomes, despite
      predominantly consuming AmED for the taste and the functional and hedonistic
      outcomes. Strong endorsement of motives relating to ease of access and low cost
      price suggests that alcohol policy reform in relation to licensing restrictions
      may be necessary to minimize the risk of harm.

PMID- 22985056
TI  - Pop-up messages, dissociation, and craving: how monetary limit reminders
      facilitate adherence in a session of slot machine gambling.
AB  - A failure to set and adhere to monetary limits has been implicated in the
      development of problematic gambling. A randomized controlled experiment (N = 59)
      with 2 conditions (i.e., monetary limit pop-up reminder vs. no monetary limit pop
      up reminder) was conducted to assess the value of monetary limit pop-up messages
      in increasing adherence to self-proclaimed monetary limits. The current research
      also examined dissociation as a potential mechanism by which gambling
      symptomatology may undermine adherence to monetary limits. Results revealed that
      participants who received a monetary limit pop-up reminder were significantly
      more likely to adhere to monetary limits than participants who did not. As
      predicted, dissociation mediated the relationship between gambling symptomatology
      and adherence to monetary limits, but only among those who did not receive a
      monetary limit pop-up reminder. Importantly, the forced stop in play created by
      the pop-up message did not heighten craving to continue gambling. The efficacy of
      monetary limit pop-up messages as a tool to facilitate responsible gambling is
      discussed.

PMID- 22985058
TI  - Factors associated with the severity and improvement of fatigue in patients with
      advanced cancer presenting to an outpatient palliative care clinic.
AB  - BACKGROUND: The aim of this study was to determine factors associated with the
      severity of cancer related fatigue (CRF) and predictors of improvement of CRF at
      the first follow-up visit in patients with advanced cancer referred to outpatient
      palliative care clinic (OPC). METHODS: We reviewed the records of consecutive
      patients with advanced cancer presenting to OPC. Edmonton Symptom Assessment
      System (ESAS) scores were obtained at the initial and subsequent visits between
      January 2003 and December 2008. All patients received interdisciplinary care led
      by palliative medicine specialists following an institutional protocol. Fatigue
      improvement was defined as a reduction of >=2 points in ESAS score relative to
      the baseline. Descriptive statistics were used to summarize patient
      characterstics. Univariate analyses were performed and only significant variables
      were included in multivariate regression analysis to determine factors associated
      with severity and improvement in CRF. RESULTS: A total of 1778 evaluable patients
      were analyzed (median age, 59 years; 52% male). The median time between visits
      was 15 days. Median fatigue scores on the ESAS were 6 at baseline and 5 at follow
      up. Severity of all ESAS items and low serum albumin were associated with fatigue
      at baseline (p < 0.0001). The improvement of fatigue was observed in 586 patients
      (33%). The hierarchical model showed that fatigue improved over time (b = -0.009;
      p = 0.0009). low appetite (odds ratio [OR] = 1.09 per point; p = 0.0113) and
      genitourinary cancer (OR = 1.74 per point; p = 0.0458) were significantly
      associated with improvement of fatigue. CONCLUSIONS: CRF is strongly associated
      with physical and emotional symptoms. Genitourinary cancer and low appetite at
      baseline were associated with successful improvement of fatigue.

PMID- 22985059
TI  - Conflicting roles of nickel in controlling cathode performance in lithium ion
      batteries.
AB  - A variety of approaches are being made to enhance the performance of lithium ion
      batteries. Incorporating multivalence transition-metal ions into metal oxide
      cathodes has been identified as an essential approach to achieve the necessary
      high voltage and high capacity. However, the fundamental mechanism that limits
      their power rate and cycling stability remains unclear. The power rate strongly
      depends on the lithium ion drift speed in the cathode. Crystallographically,
      these transition-metal-based cathodes frequently have a layered structure. In the
      classic wisdom, it is accepted that lithium ion travels swiftly within the layers
      moving out/in of the cathode during the charge/discharge. Here, we report the
      unexpected discovery of a thermodynamically driven, yet kinetically controlled,
      surface modification in the widely explored lithium nickel manganese oxide
      cathode material, which may inhibit the battery charge/discharge rate. We found
      that during cathode synthesis and processing before electrochemical cycling in
      the cell nickel can preferentially move along the fast diffusion channels and
      selectively segregate at the surface facets terminated with a mix of anions and
      cations. This segregation essentially can lead to a higher lithium diffusion
      barrier near the surface region of the particle. Therefore, it appears that the
      transition-metal dopant may help to provide high capacity and/or high voltage but
      can be located in a "wrong" location that may slow down lithium diffusion,
      limiting battery performance. In this circumstance, limitations in the properties
      of lithium ion batteries using these cathode materials can be determined more by
      the materials synthesis issues than by the operation within the battery itself.

PMID- 22985057
TI  - Review of the application of positive psychology to substance use, addiction, and
      recovery research.
AB  - Advances in positive psychology have grown exponentially over the past decade.
      The addictions field has experienced its own growth in a positive direction,
      embodied by the recovery movement. Despite parallel developments, and great
      momentum on both sides, there has been little crosspollination. This article
      introduces positive psychology and the recovery movement, describes the research
      on positive psychology in the addictions, and discusses future avenues of theory,
      research, and intervention based on a positive-psychology framework. A systematic
      review of positive psychology applied to substance use, addiction, and recovery
      found nine studies which are discussed according to the following themes:
      theoretical propositions, character strengths and drinking, positive psychology
      and recovery, positive interventions, and addiction: feeling good and feeling
      bad. The current scholarship is scant, but diverse, covering a wide range of
      populations (adults, adolescents, those in and out of treatment), topics
      (character strengths, recovery, positive affect), and addictive behaviors (work
      addiction, cigarette smoking, and alcohol use disorders). There is diversity,
      too, in country of origin, with work originating in the U.S., U.K., Poland, and
      Spain. The rigorous application of the lens, tools, and approaches of positive
      psychology to addiction research generally, and to the aims of the recovery
      movement specifically, has potential for the development of theory and innovation
      in prevention and intervention. Further, because the work in positive psychology
      has primarily focused on microsystems, it may be primed to make contributions to
      the predominantly macrosystems focus of the recovery movement. (PsycINFO Database
      Record (c) 2013 APA, all rights reserved).

PMID- 22985060
TI  - Prevalence of infection as a predictor of multiple genotype infection frequency
      in parasites with multiple-host life cycle.
AB  - In nature, parasites commonly share hosts with other conspecific parasite
      genotypes. While adult parasites typically show aggregated distribution in their
      final hosts, aggregation of clonal parasite genotypes in intermediate hosts, such
      as those of trematodes in molluscs, is not generally known. However, infection of
      a host by multiple parasite genotypes has significant implications for evolution
      of virulence and host-parasite coevolution. Aggregated distribution of the clonal
      stages can increase host mortality and reduce larval output of each infecting
      genotype through interclonal competition, and therefore have significant
      implications for parasite epidemiology. The aim of this study was (i) to find out
      how common multiple genotype infections (MGIs) are in aquatic snails serving as
      intermediate hosts for different trematode species; (ii) to find out whether the
      prevalence of infection could be used to predict MGI frequencies and (iii) to use
      the relationship to infer whether MGIs aggregate in molluscan hosts. We
      determined the prevalence of trematode (Diplostomum pseudospathaceum) infections
      and the frequency of MGIs in snail (Lymnaea stagnalis) host populations as well
      as compiled corresponding literature data from a range of snail-trematode
      systems. We used Bayesian simulations to explore the relationship between
      prevalence of infection and MGI frequency in these data, and tested whether
      genotypes aggregate in snails by comparing the simulated relations with null
      model (Poisson and demographic Poisson) expectations. Our results show that MGIs
      are common in aquatic snails with up to 90% of the infected snails carrying MGIs.
      Parasite prevalence is a good predictor of MGI frequencies at a range of
      prevailing natural prevalences of infection (0-50%). The frequency of MGIs was
      higher than expected by both null models, indicating parasite aggregation at
      genotype level. These findings are in sharp contrast with the absence of multiple
      infections in snails at level of trematode species, suggesting that co-infections
      by multiple species and multiple genotypes of one species are controlled by
      different biological processes. Aggregation of MGIs in snail hosts appears to be
      widespread across different snail-trematode systems.

PMID- 22985061
TI  - Telomerase activity and telomere length distribution in vascular endothelial
      cells in a short-term culture under the presence of hydrogen peroxide.
AB  - AIM: The aim of this study was to assess the biological effects of oxidative
      stress on human vascular endothelial cells. METHODS: The telomeric changes and
      the alterations of the expression of telomere-associated proteins in human
      umbilical venous endothelial cells (HUVEC) cultured in the presence of hydrogen
      peroxide (H2 O2 ) were analyzed. RESULTS: During the culture, the cell growth
      rate decreased, whereas the telomerase activity of the surviving cells increased.
      As the H2 O2 level increased, long telomeres decreased proportionally, thus
      resulting in a telomere length distribution that was rich in short telomeres.
      These observations suggested that H2 O2 -affected endothelial cells bear
      telomeric features similar to those of aged cells. In contrast, the expression of
      telomere-associated proteins, TRF1 and TRF2, showed different changes. TRF1
      increased in relation to H2 O2 concentration, whereas TRF2 showed no significant
      change. The surviving cells exposed to H2 O2 showed a H2 O2 -dose dependent
      increase in telomerase activity, whereas the telomere protein and RNA components
      were only elevated in low concentrations of H2 O2 . CONCLUSIONS: The increase in
      telomerase activity and TRF1 protein expression of vascular endothelial cell
      might show an aspect of cellular protective reaction against oxygen stress.

PMID- 22985062
TI  - Release of dissolved carbohydrates by Emiliania huxleyi and formation of
      transparent exopolymer particles depend on algal life cycle and bacterial
      activity.
AB  - The coccolithophore Emiliania huxleyi plays a pivotal role in the marine carbon
      cycle. However, we have only limited understanding of how its life cycle and
      bacterial interactions affect the production and composition of dissolved
      extracellular organic carbon and its transfer to the particulate pool. We traced
      the fate of photosynthetically fixed carbon during phosphate-limited stationary
      growth of non-axenic, calcifying E. huxleyi batch cultures, and more specifically
      the transfer of this carbon to bacteria and to dissolved high molecular weight
      neutral aldoses (HMW NAld) and extracellular particulate carbon. We then compared
      the dynamics of dissolved carbohydrates and transparent exopolymer particles
      (TEP) between cultures of non-axenic and axenic diploid E. huxleyi. In addition,
      we present the first data on extracellular organic carbon in (non-axenic) haploid
      E. huxleyi cultures. Bacteria enhanced the accumulation of dissolved
      polysaccharides and altered the composition of dissolved HMW NAld, while they
      also stimulated the formation of TEP containing high densities of charged
      polysaccharides in diploid E. huxleyi cultures. In haploid E. huxleyi cultures we
      found a more pronounced accumulation of dissolved carbohydrates, which had a
      different NAld composition than the diploid cultures. TEP formation was
      significantly lower than in the diploid cultures, despite the presence of
      bacteria. In diploid E. huxleyi cultures, we measured a high level of
      extracellular release of organic carbon (34-76%), retrieved mainly in the
      particulate pool instead of the dissolved pool. Enhanced formation of sticky TEP
      due to bacteria-alga interactions, in concert with the production of coccoliths,
      suggests that especially diploid E. huxleyi blooms increase the efficiency of
      export production in the ocean during dissolved phosphate-limited conditions.

PMID- 22985064
TI  - Microbiological assessment of four probiotic feed supplements used by the dairy
      industry in New Zealand.

PMID- 22985063
TI  - Physical violence and health-related quality of life: Danish cross-sectional
      analyses.
AB  - BACKGROUND: The aim of this study was to evaluate the association between
      experienced physical violence and health-related quality of life (HRQoL) by
      comparing self-reported health status for individuals with and without experience
      of physical violence. Our hypothesis was that individuals exposed to violence
      would experience worse HRQoL than non-exposed individuals. We tested whether men
      and women and different age groups experience similar reductions in HRQoL, and
      the extent to which such differences might be associated with social
      circumstances and lifestyle conditions. Finally, we explored the HRQoL
      consequences of exposure to violence in a longer time perspective. METHODS: We
      used data from self-completed questionnaires in two Danish nationally
      representative, cross-sectional health interview surveys. Exposure to violence
      was indicated through specific survey questions (Straus' conflict tactics scale)
      enquiring about different types of violence during the last 12 months. Health
      status of respondents was elicited by the EQ-5D and SF-36 questionnaires. The
      health status profiles were converted to health score indexes using the Danish
      algorithm for EQ-5D and the revised Brazier algorithm for SF-6D. Differences in
      score indexes between the exposed and non-exposed individuals were explored
      separately for men and women using ordinary least square regression with four age
      categories as explanatory variables. RESULTS: In the 2000 and 2005 surveys,
      respectively, 4.9% and 5.7% of respondents indicated that they had been exposed
      to physical violence within the last 12 months. Exposure to violence was more
      prevalent in the younger age groups and more prevalent for men than women.
      Respondents exposed to violence had lower score indexes on both the EQ-5D and the
      SF-6D compared with the non-exposed. Respondents who reported exposure to
      violence in both 2000 and 2005 reported lower HRQoL than individuals who only
      reported exposure in one of the surveys. CONCLUSIONS: The results of this study
      provide evidence for an association between exposure to physical violence and
      reduction in health-related quality of life.

PMID- 22985065
TI  - Biotechnological approaches for the production of prebiotics and their potential
      applications.
AB  - Worldwide interest in prebiotics have been increasing extensively both as food
      ingredients and pharmacological supplements, since they have beneficial
      properties for human health. Prebiotics not only stimulate the growth of healthy
      bacteria such as bifidobacteria and lactobacilli in the gut but also increase the
      resistance towards pathogens. In addition to this, they also act as dietary
      fiber, an energy source for intestinal cells after converting to short-chain
      fatty acids, a stimulator of immune systems, sugar replacer etc. Moreover, due to
      heat resistant properties, they are able to maintain their intact form during the
      baking process and allow them to be incorporated into every day food products.
      Thus, they can be interesting and useful ingredients in the development of novel
      functional foods. This review provides comprehensive information about the
      different biotechnological techniques employed in the production of prebiotics
      and their potential applications in different areas. 

PMID- 22985067
TI  - Thermodynamic parameters of electrochemical oxidation of L-DOPA: experimental and
      theoretical studies.
AB  - Electrode potential and thermodynamic parameters of the electrochemical reaction
      of L-DOPA in aqueous solution are obtained experimentally by cyclic voltammetry
      method and also calculated theoretically using accurate ab initio calculations
      (G3MP2//B3LYP) along with the available solvation model of CPCM. The pH
      dependence of the redox activity of L-DOPA in aqueous solution at temperatures in
      the range of 10-30  degrees C was used for the experimental determination of the
      standard reduction potential, changes of entropy, enthalpy, and Gibbs free energy
      for the studied reaction. The experimental formal redox potential of the two
      proton-two-electron reduction process was obtained to be 0.745 V versus standard
      hydrogen electrode (SHE). The theoretical and experimental values (0.728 and
      0.745 V) for the standard electrode potential of L-DOPA are in agreement with
      each other. The difference between the peak potential of the L-DOPA and the
      products, which are produced by chemical reactions, has been measured
      experimentally and also calculated theoretically. There is also an agreement
      between experimental and theoretical potential difference. Also in this work, the
      changes of thermodynamic functions of solvation are calculated from the
      differences between the solution-phase experimental values and the gas-phase
      theoretical values.

PMID- 22985066
TI  - Effects of laparoscopic radical surgery for deep endometriosis on endometriosis
      related pelvic pain.
AB  - Deep endometriosis is associated with severe painful symptoms that sometimes
      impair the quality of life in women of reproductive age. Medical therapy does not
      provide for adequate pain relief, and an effective management option to reduce
      pelvic pain appears to be complete laparoscopic removal of as many endometriotic
      lesions as possible. In this study, we investigated the usefulness and risks of
      radical laparoscopic removal of deep endometriosis for patients diagnosed as
      stage III/IV endometriosis during laparoscopic surgery. Forty-seven consecutive
      patients undergoing conservative laparoscopic surgery alone (adhesiotomy and
      cystectomy of ovarian endometriosis but not removal of deep endometriotic lesion;
      non-DEL removal group) and 151 consecutive patients undergoing radical
      laparoscopic removal of deep endometriotic lesions combined with conservative
      surgery (DEL removal group) were compared. As a result, significant improvements
      in pain were obtained in both groups, however, the degree of improvement was
      significantly higher and the rate of recurrence was significantly lower in the
      DEL removal group. The addition of radical removal of deep endometriotic lesions
      to conservative laparoscopic surgery markedly reduces the severity of
      dysmenorrhea and the rate of recurrent pelvic pain. Although the surgical
      procedure is technically demanding, the levels of peri-operative complications
      and morbidity are acceptable.

PMID- 22985068
TI  - A dictionary based informational genome analysis.
AB  - BACKGROUND: In the post-genomic era several methods of computational genomics are
      emerging to understand how the whole information is structured within genomes.
      Literature of last five years accounts for several alignment-free methods, arisen
      as alternative metrics for dissimilarity of biological sequences. Among the
      others, recent approaches are based on empirical frequencies of DNA k-mers in
      whole genomes. RESULTS: Any set of words (factors) occurring in a genome provides
      a genomic dictionary. About sixty genomes were analyzed by means of informational
      indexes based on genomic dictionaries, where a systemic view replaces a local
      sequence analysis. A software prototype applying a methodology here outlined
      carried out some computations on genomic data. We computed informational indexes,
      built the genomic dictionaries with different sizes, along with frequency
      distributions. The software performed three main tasks: computation of
      informational indexes, storage of these in a database, index analysis and
      visualization. The validation was done by investigating genomes of various
      organisms. A systematic analysis of genomic repeats of several lengths, which is
      of vivid interest in biology (for example to compute excessively represented
      functional sequences, such as promoters), was discussed, and suggested a method
      to define synthetic genetic networks. CONCLUSIONS: We introduced a methodology
      based on dictionaries, and an efficient motif-finding software application for
      comparative genomics. This approach could be extended along many investigation
      lines, namely exported in other contexts of computational genomics, as a basis
      for discrimination of genomic pathologies.

PMID- 22985069
TI  - Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and
      implications for inhibitor design.
AB  - A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of
      6-amino-pyrazolopyrimidinone have been discovered by a combination of structure
      based design and computational docking. This procedure significantly saved the
      load of chemical synthesis and is an effective method for the discovery of
      inhibitors. The best compound 28 has an IC(50) of 21 nM and 3.3 MUM,
      respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity
      against other PDE families. The crystal structure of the PDE9 catalytic domain in
      complex with 28 has been determined and shows a hydrogen bond between 28 and
      Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against
      PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our
      studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential
      target for improvement of selectivity of PDE9 inhibitors.

PMID- 22985071
TI  - Top-down approach for the direct characterization of low molecular weight
      heparins using LC-FT-MS.
AB  - Low molecular heparins (LMWHs) are structurally complex, heterogeneous,
      polydisperse, and highly negatively charged mixtures of polysaccharides. The
      direct characterization of LMWH is a major challenge for currently available
      analytical technologies. Electrospray ionization (ESI) liquid chromatography-mass
      spectrometry (LC-MS) is a powerful tool for the characterization complex
      biological samples in the fields of proteomics, metabolomics, and glycomics. LC
      MS has been applied to the analysis of heparin oligosaccharides, separated by
      size exclusion, reversed phase ion-pairing chromatography, and chip-based amide
      hydrophilic interaction chromatography (HILIC). However, there have been limited
      applications of ESI-LC-MS for the direct characterization of intact LMWHs (top
      down analysis) due to their structural complexity, low ionization efficiency, and
      sulfate loss. Here we present a simple and reliable HILIC-Fourier transform (FT)
      ESI-MS platform to characterize and compare two currently marketed LMWH products
      using the top-down approach requiring no special sample preparation steps. This
      HILIC system relies on cross-linked diol rather than amide chemistry, affording
      highly resolved chromatographic separations using a relatively high percentage of
      acetonitrile in the mobile phase, resulting in stable and high efficiency
      ionization. Bioinformatics software (GlycReSoft 1.0) was used to automatically
      assign structures within 5-ppm mass accuracy.

PMID- 22985073
TI  - Ruthenium stilbenyl and diruthenium distyrylethene complexes: aspects of electron
      delocalization and electrocatalyzed isomerization of the Z-isomer.
AB  - Regio- and stereoselective insertion of the terminal ethynyl functions of 4
      ethynylstilbene, the E and Z isomers of 4,4'-bis(ethynylphenyl)ethene and a
      backbone-rigidified cyclohexenyl derivative of the Z isomer into the Ru-H bond of
      the complex RuClH(CO)(P(i)Pr(3))(2) provides the corresponding vinyl ruthenium
      complexes, which have been characterized spectroscopically and by X-ray
      crystallography. Large red shifts of the UV/vis absorption bands evidence
      efficient incorporation of the vinyl metal subunit(s) into the conjugated pi
      system. All complexes oxidize at low potentials. The various oxidized forms of
      all complexes were generated and characterized by UV/vis/NIR, IR and EPR
      spectroscopies. These studies indicated electrocatalytic Z->E isomerization of
      the oxidized Z-distyrylethene complex Ru-Z2, which is prevented in its backbone
      rigidified derivative Ru-Z2fix. The radical cations of the E and the
      configurationally stable cyclohexene-bridged Z-derivatives are spin-delocalized
      on the EPR time scale but charge-localized on the faster IR time scale. The
      degree of ground-state charge delocalization in the mixed-valent state has been
      quantified by the incremental shifts of the Ru-CO bands upon stepwise oxidation
      to the radical cations and the dications and was found to be remarkably large
      (19% and 9%) considering redox splittings DeltaE(1/2) of just 49 or 74 mV.
      Quantum chemical studies with various levels of sophistication reproduce our
      experimental results including the electronic spectra of the neutral complexes
      and the intrinsically localized nature of the radical cations of the dinuclear
      complexes.

PMID- 22985072
TI  - Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic
      dyskinesia.
AB  - BACKGROUND: Recently, heterozygous mutations in PRRT2 (Chr 16p11.2) have been
      identified in Han Chinese, Japanese and Caucasians with paroxysmal kinesigenic
      dyskinesia. In previous work, a paroxysmal kinesigenic dyskinesia locus was
      mapped to Chr 16p11.2 - q11.2 in a multiplex African-American family. METHODS:
      Sanger sequencing was used to analyze all four PRRT2 exons for sequence variants
      in 13 probands (9 Caucasian, 1 Caucasian-Thai, 1 Vietnamese and 2 African
      American) with some form of paroxysmal dyskinesia. RESULTS: One patient of mixed
      Caucasian-Thai background and one African-American family harbored the previously
      described hotspot mutation in PRRT2 (c.649dupC, p.R217Pfs*8). Another African
      American family was found to have a novel mutation (c.776dupG, p.E260*). Both of
      these variants are likely to cause loss-of-function via nonsense-mediated decay
      of mutant PRRT2 transcripts. All affected individuals had classic paroxysmal
      kinesigenic dyskinesia phenotypes. CONCLUSIONS: Heterozygous PRRT2 gene mutations
      also cause paroxysmal kinesigenic dyskinesia in African-Americans. The c.649dupC
      hotspot mutation in PRRT2 is common across racial groups.

PMID- 22985074
TI  - Resolution and recurrence of vitiligo following excision of congenital
      melanocytic nevus.
AB  - Vitiligo associated with halo congenital melanocytic nevus (CMN) is rare. There
      are limited reports in the literature, especially with regard to CMN excision. We
      present the case of a 5-year-old girl who presented with vitiligo of the
      periorbital and axillary regions and halo formation around CMN of the buttock.
      The lesion was excised, and all areas of vitiligo improved, but 18 months
      postoperatively, a halo of depigmentation appeared around the excision scar and
      later in the periorbital and axillary regions. In review of literature, there is
      only one report of excision of halo CMN and resultant improvement of vitiligo.
      Although initial resolution of vitiligo in this case was promising, the
      recurrence indicates that this complex process is not reliably controlled with
      excision of the inciting lesion.

PMID- 22985075
TI  - Quality and safety issues in procedural rural practice: a prospective evaluation
      of current quality and safety guidelines in 3000 colonoscopies.
AB  - INTRODUCTION: Colonoscopy remains the gold standard for the investigation and
      management of bowel pathology. A 2009 National Bowel Cancer Screening Program
      Quality Working Group report revealed that small rural towns in inner regional
      Victoria, Australia, for example Echuca (Rural and Remote Metropolitan Areas
      [RRMA] 4), registered 10.5 colonoscopies per 1000 population versus 18.5 per 1000
      in the state capital Melbourne. Reasons for this discrepancy include lack of
      skilled practitioners in rural communities and travel time for patients to attend
      larger centres when the required bowel preparation or mobility issues limit
      access. Ideally, services are high quality, safe and local. This study assessed
      the quality and safety of a rural GP colonoscopy service. METHODS: The
      indications, findings, caecal intubation rates, complications and completion time
      were recorded for 3000 serial colonoscopies performed by one rural procedural GP
      from 1995 to 2011 in Victorian Echuca. Quality was assessed using caecal
      intubation rate, polyp and colorectal carcinoma detection rates, and completion
      time. Safety was determined by complication rates. RESULTS: The caecal intubation
      rate was 97% (excluding stenosing lesions), polypectomy detection rate was 39%,
      carcinoma detection rate was 2%, and the average time to completion was 17 min.
      Re-admission rates were 1.6/1000 for haemorrhage and 1.2/1000 for perforation.
      There were no deaths. CONCLUSIONS: The results from this study compare favourably
      with published international standards, validate Australian general practice
      procedural training standards, and validate the additional quality measure of
      'colonoscopy completion time'. Rural GPs can provide a safe and high quality
      service. Extending this service model to similar settings could improve reduced
      access to colonoscopy for rural Australians.

PMID- 22985076
TI  - Spinal cord stimulation (SCS) in conjunction with peripheral nerve field
      stimulation (PNfS) for the treatment of complex pain in failed back surgery
      syndrome (FBSS).
AB  - BACKGROUND: Failed back surgery syndrome (FBSS) is a well-defined pathologic
      condition observed over many years. DESIGN: We have investigated the effect of
      spinal cord stimulation (SCS) with peripheral nerve field stimulation (PNfS) in
      eight patients with FBSS. OUTCOME MEASURE: The following parameters were
      collected and analyzed: The pain intensity score on a 0-10 numbering rating scale
      (NRS), the psychologic profile with Beck Depression Inventory (BDI), the pain
      quality with McGill Pain Questionnaire-short form (MGPQ-sf), the back pain with
      Oswestry scale score (OS), and the health general quality pattern with
      QualityMetric's SF-36v2((r)) Health Survey. PATIENTS: Eight patients with low
      back and radicular pain in FBSS are reported. The mean duration of pain was 6.7
      months, and the mean NRS score was 9.5, BDI 28.8, MGPQ-sf 16.8, OS 44.5, and SF
      36 score was 72.8. The average drug intake of opioids was 250 mg/day.
      INTERVENTION: In six patients, two octopolar leads were placed in epidural space
      at D7-D8 and D8-D9, in conjunction with two octopolar leads placed in lumbar
      sacral subcutaneous space (Precision System, Boston Scientific, Valencia, CA,
      USA), and in two patients, a two tetrapolar leads was placed in epidural space at
      D8-D9 with two tetrapolar leads (Pisces Quad, Plus, Medtronic Inc., Minneapolis,
      MN, USA) placed in lumbar-sacral subcutaneous space (Restore Ultra, Medtronic
      Inc., Minneapolis, MN, USA). RESULTS: After one year mean of follow-up, the mean
      NRS score was 4, BDI 8, MGPQ-sf 5, OS 21, and the SF-36 score was increased at
      108.5. The mean drug intake of opioids was decreased at 20 mg/day. CONCLUSION:
      The combination of SCS and PNfS, using the latest rechargeable systems, may be a
      valid therapeutic strategy in FBSS.

PMID- 22985077
TI  - Associations between genetic polymorphisms of beta-2 adrenergic receptor and
      preterm delivery in Korean women.
AB  - PROBLEM: We investigated genetic polymorphisms to understand the etiology of
      preterm delivery, which involves inflammatory cytokines and uterine contraction.
      Maternal polymorphisms of ADRB2, iNOS, and eNOS were examined, and associations
      between these and the risk of preterm delivery were sought. METHOD OF STUDY: This
      study was performed on 166 Korean women who underwent preterm delivery and 289
      normal controls. Logistic regression analyses were carried out to identify single
      genes and haplotypes that affect the risk of preterm delivery. RESULTS: The G/G
      haplotype of ADRB2-rs1042713 and -rs1042714 was found to be associated with the
      risk of preterm delivery (OR = 1.90, 95% CI = 1.08-3.33, P-value = 0.0252). The
      genotype frequency of G allele in ADRB2-rs1042714 was associated with increased
      the risk of preterm delivery. However, after the adjustment of multiple
      comparison corrections, the association with preterm delivery was not remained
      significantly. CONCLUSION: These findings possibly aid our understanding of the
      pathogenesis of preterm delivery and suggest that a haplotype with variants in
      maternal genes involved in adrenergic activation may lead to the dysregulation of
      uterine contractility and increase the risk of preterm delivery.

PMID- 22985079
TI  - Analysis of state-specific vibrations coupled to the unidirectional energy
      transfer in conjugated dendrimers.
AB  - The nonadiabatic excited-state molecular dynamics (NA-ESMD) method and excited
      state instantaneous normal modes (ES-INMs) analyses have been applied to describe
      the state-specific vibrations that participate in the unidirectional energy
      transfer between the coupled chromophores in a branched dendrimeric molecule. Our
      molecule is composed of two-, three-, and four-ring linear
      poly(phenyleneethynylene) (PPE) units linked through meta-substitutions. After an
      initial laser excitation, an ultrafast sequential S(3) -> S(2) -> S(1) electronic
      energy transfer from the shortest to longest segment takes place. During each
      S(n) -> S(n-1) (n = 3, 2) transition, ES-INM(S(n)) and ES-INM(S(n-1)) analyses
      have been performed on S(n) and S(n-1) states, respectively. Our results reveal a
      unique vibrational mode localized on the S(n) state that significantly matches
      with the corresponding nonadiabatic coupling vector d(n,(n-1)). This mode also
      corresponds to the highest frequency ES-INM(S(n)) and it is seen mainly during
      the electronic transitions. Furthermore, its absence as a unique ES-INM(S(n-1))
      reveals that state-specific vibrations play the main role in the efficiency of
      the unidirectional S(n) -> S(n-1) electronic and vibrational energy funneling in
      light-harvesting dendrimers.

PMID- 22985080
TI  - Stability and segregation of B and P dopants in Si/SiO2 core-shell nanowires.
AB  - Using molecular dynamics simulations, we generate realistic atomic models for
      oxidized Si nanowires which consist of a crystalline Si core and an amorphous
      SiO(2) shell. The amorphous characteristics of SiO(2) are well reproduced, as
      compared to those for bulk amorphous silica. Based on first-principles density
      functional calculations, we investigate the stability and segregation of B and P
      dopants near the radial interface between Si and SiO(2). Although substitutional
      B atoms are more stable in the core than in the oxide, B dopants can segregate to
      the oxide with the aid of Si self-interstitials which are generated during
      thermal oxidation. The segregation of B dopants occurs in the form of B
      interstitials in the oxide, leaving the self-interstitials in the Si core. In the
      case of P dopants, dopant segregation to the oxide is unfavorable even in the
      presence of self-interstitials. Instead, we find that P dopants tend to aggregate
      in the Si region near the interface and may form nearest-neighbor donor pairs,
      which are energetically more stable than isolated P dopants.

PMID- 22985082
TI  - A note on the aggregation of event probabilities.
AB  - In this article, multiple forecasts given as probabilities of events are
      aggregated using two assumptions: calibration and conditional independence. The
      forecasts are treated as data and the aggregation is based on Bayes's theorem. A
      measure of discrimination is given and the behavior of the aggregated posterior
      probability is examined as the number of forecasters grows without bound. The
      work is motivated by recent research efforts employing large numbers of
      individual forecasts.

PMID- 22985081
TI  - Suboptimal chemotherapy is an adverse prognostic factor in osteosarcoma.
AB  - BACKGROUND: We sought to determine whether suboptimal chemotherapy compromised
      the prognosis of osteosarcoma patients. METHODS: A total of 132 eligible patients
      who underwent chemotherapy between 1998 and 2008 were identified in our database.
      Information regarding patient demographics, clinical characteristics, and
      survival status were extracted for analysis. Optimal chemotherapy was defined as
      receipt of >=80% of the planned dose intensity of prescribed agents within the
      planned durations. RESULTS: The use of optimal chemotherapy resulted in an
      overall survival benefit with P = 0.006. Patients who failed to complete the
      optimal chemotherapy protocol had a dismal prognosis of 30.8% overall survival
      over five years, whereas those who completed the optimal chemotherapy had an
      overall survival rate over five years of 65.3%. Based on multivariate analysis,
      patients who were treated with a suboptimal protocol had a higher risk of
      relapse, metastasis and mortality. The hazard ratio (HR) of recurrence or death
      for the suboptimal chemotherapy group was as high as 2.512 over that of the
      optimal chemotherapy group (HR = 2.512, 95% confidence interval = 1.242 to
      3.729). CONCLUSIONS: Chemotherapy is a significant independent prognostic
      variable, and suboptimal chemotherapy was found to have a detrimental effect on
      the outcome of patients with osteosarcoma.

PMID- 22985083
TI  - Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.
AB  - A retrospective study was performed to assess toxicity and response rate of
      ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma
      (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy
      were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs
      were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2)
      (median dose 375 mg m(-2)), with a median of two doses administered per dog
      (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete
      response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17,
      progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide
      toxicosis. The median survival duration from the first dose of ifosfamide to
      death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity
      was observed.

PMID- 22985084
TI  - Gender-specific association between FSHR and PPARG common variants and human
      longevity.
AB  - Men and women have different life expectancies. Not unexpectedly, several genes
      involved in life span determination have been found to influence the probability
      of achieving longevity differently in men and women. This investigation examines
      the association between longevity and polymorphisms of follicle-stimulating
      hormone receptor (FSHR, Asn680Ser polymorphism) and peroxisome proliferator
      activated receptor gamma (PPARG, Pro12Ala polymorphism), two genes that previous
      investigations suggested may exert a gender-specific influence on human
      longevity. A sample of 277 individuals (mean age, 82.9+/-5.7years) was recruited
      in 2000. On the basis of mortality data collected in 2009, the sample was divided
      into two groups of subjects surviving over 90 years (long-lived) or not
      (controls). The frequency of the FSHR 680 Ser/Ser genotype was significantly
      higher in the sample of long-lived women compared to controls, indicating that
      the FSHR 680 Ser/Ser genotype may favor survival to more than 90 years of age
      only in women (odds ratio [OR]=4.21; 95% confidence interval [CI], 1.10-16.10,
      p=0.036). In contrast, the frequency of the PPARG Pro/Ala genotype was
      significantly higher in the sample of male subjects who died before 90 years of
      age than in the long-lived, suggesting that carrying the PPARG Pro/Ala genotype
      may prevent the attainment of advanced age only in men (OR=0.13; 95% CI, 0.02
      0.79; p=0.03). We then searched the literature for studies reporting a
      differential role for the genetic component in male and female longevity. To do
      this, we selected longevity genes with a gender-specific effect. A review of the
      studies showed that genetic factors tend to have a greater relevance in
      determining longevity in men than in women. The possible impact of this
      phenomenon is discussed.

PMID- 22985085
TI  - Enterohaemorrhagic Escherichia coli O157:H7 Shiga-like toxin 1 is required for
      full pathogenicity and activation of the p38 mitogen-activated protein kinase
      pathway in Caenorhabditis elegans.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) causes life-threatening infections in
      humans as a consequence of the production of Shiga-like toxins. Lack of a good
      animal model system currently hinders in vivo study of EHEC virulence by
      systematic genetic methods. Here we applied the genetically tractable animal,
      Caenorhabditis elegans, as a surrogate host to study the virulence of EHEC as
      well as the host immunity to this human pathogen. Our results show that E. coli
      O157:H7, a serotype of EHEC, infects and kills C. elegans. Bacterial colonization
      and induction of the characteristic attaching and effacing (A/E) lesions in the
      intact intestinal epithelium of C. elegans by E. coli O157:H7 were concomitantly
      demonstrated in vivo. Genetic analysis indicated that the Shiga-like toxin 1
      (Stx1) of E. coli O157:H7 is a virulence factor in C. elegans and is required for
      full toxicity. Moreover, the C. elegans p38 mitogen-activated protein kinase
      (MAPK) pathway, an evolutionarily conserved innate immune and stress response
      signalling pathway, is activated in the regulation of host susceptibility to EHEC
      infection in a Stx1-dependent manner. Our results validate the EHEC-C. elegans
      interaction as suitable for future comprehensive genetic screens for both novel
      bacterial and host factors involved in the pathogenesis of EHEC infection.

PMID- 22985087
TI  - Characterization of an antigenic chitosanase from the cellulolytic fungus
      Chaetomium globosum.
AB  - We are interested in identifying human fungal allergens and antigens from species
      common on water-damaged or damp building materials for use as marker proteins and
      diagnostic tests. The cellulolytic fungus Chaetomium globosum is common on damp
      materials in the building environment worldwide. ELISA and immunoblotting tests
      identified two related proteins of molecular weights 45 and 47 kDa which were
      identified as fungal antigens found on spore surfaces and in culture filtrate.
      The sequences were determined by liquid chromatography tandem mass spectrometry
      (LC-MS/MS), which indicated that the two proteins were chitosanases, confirmed by
      enzyme assay. The 47 kDa protein was not glycosylated and had an acidic pI of
      4.5. These proteins have not been reported from other fungi and similar antigens
      were not seen in other fungi common in buildings. The production of polyclonal
      antibodies in rabbits showed the antigenicity of the target proteins and
      confirmed they were not artifacts of the isolation process. The proteins isolated
      are useful biomarkers for the detection of C. globosum in the building
      environment.

PMID- 22985089
TI  - Foxtail millet: a model crop for genetic and genomic studies in bioenergy
      grasses.
AB  - Foxtail millet is one of the oldest domesticated diploid C4 Panicoid crops having
      a comparatively small genome size of approximately 515 Mb, short life cycle, and
      inbreeding nature. Its two species, Setaria italica (domesticated) and Setaria
      viridis (wild progenitor), have characteristics that classify them as excellent
      model systems to examine several aspects of architectural, evolutionary, and
      physiological importance in Panicoid grasses especially the biofuel crops such as
      switchgrass and napiergrass. Foxtail millet is a staple crop used extensively for
      food and fodder in parts of Asia and Africa. In its long history of cultivation,
      it has been adapted to arid and semi-arid areas of Asia, North Africa, South and
      North America. Foxtail millet has one of the largest collections of cultivated as
      well as wild-type germplasm rich with phenotypic variations and hence provides
      prospects for association mapping and allele-mining of elite and novel variants
      to be incorporated in crop improvement programs. Most of the foxtail millet
      accessions can be primarily abiotic stress tolerant particularly to drought and
      salinity, and therefore exploiting these agronomic traits can enhance its
      efficacy in marker-aided breeding as well as in genetic engineering for abiotic
      stress tolerance. In addition, the release of draft genome sequence of foxtail
      millet would be useful to the researchers worldwide in not only discerning the
      molecular basis of biomass production in biofuel crops and the methods to improve
      it, but also for the introgression of beneficial agronomically important
      characteristics in foxtail millet as well as in related Panicoid bioenergy
      grasses.

PMID- 22985088
TI  - Enhanced sensing of nucleic acids with silicon nanowire field effect transistor
      biosensors.
AB  - Silicon nanowire (SiNW) field effect transistors (FETs) have emerged as powerful
      sensors for ultrasensitive, direct electrical readout, and label-free
      biological/chemical detection. The sensing mechanism of SiNW-FET can be
      understood in terms of the change in charge density at the SiNW surface after
      hybridization. So far, there have been limited systematic studies on fundamental
      factors related to device sensitivity to further make clear the overall effect on
      sensing sensitivity. Here, we present an analytical result for our triangle cross
      section wire for predicting the sensitivity of nanowire surface-charge sensors.
      It was confirmed through sensing experiments that the back-gated SiNW-FET sensor
      had the highest percentage current response in the subthreshold regime and the
      sensor performance could be optimized in low buffer ionic strength and at
      moderate probe concentration. The optimized SiNW-FET nanosensor revealed
      ultrahigh sensitivity for rapid and reliable detection of target DNA with a
      detection limit of 0.1 fM and high specificity for single-nucleotide polymorphism
      discrimination. In our work, enhanced sensing of biological species by
      optimization of operating parameters and fundamental understanding for SiNW FET
      detection limit was obtained.

PMID- 22985090
TI  - Papular epidermal nevus with "skyline" basal cell layer (PENS) with
      extracutaneous findings.
AB  - Papular epidermal nevus with "skyline" basal cell layer (PENS), a variant of
      epidermal nevus, was recently described in otherwise normal children. We describe
      herein a patient with multiple, typical PENS lesions associated with peculiar
      facies, bilateral Achilles tendon shortening, and mild psychomotor delay. The
      association of PENS with extracutaneous manifestations suggests the possibility
      of a new type of epidermal nevus syndrome, for which we propose the term PENS
      syndrome. 

PMID- 22985091
TI  - Altered expression of succinic dehydrogenase in asthenozoospermia infertile male.
AB  - PROBLEM: There is a possibility that mitochondrial respiration defects may
      contribute to asthenozoospermia. METHOD OF STUDY: Immunocytochemical detection
      was used to localize succinic dehydrogenase (SDH) in the head and mid-piece of
      spermatozoa by fluorescent microscope. RESULTS: The study revealed dispersed SDH
      activity in the semen of asthenozoospermic subjects in comparison with control
      semen samples. While the stain intensity varied from cell to cell in controls as
      well as in patients, it was predominantly localized within mid-piece of
      spermatozoa in healthy individuals. In contrast, in semen of infertile male, the
      diffused and dispersed SDH immunoreactivity was observed in head as well as in
      mid-piece region of spermatozoa. CONCLUSION: Dispersed expression of
      mitochondrial SDH in head and mid-piece of spermatozoa of asthenozoospermia
      subjects indicates mitochondrial damage because of metabolic or genetic factors,
      affecting energy production and leading to disturbed sperm motility, which could
      be pathologically significant. Detailed mitochondrial SDH immunolocalization
      studies are warranted to establish a role of deranged tricarboxylic acid cycle in
      causation of male infertility.

PMID- 22985092
TI  - The differential effects of maternal age, race/ethnicity and insurance on
      neonatal intensive care unit admission rates.
AB  - BACKGROUND: Maternal race/ethnicity, age, and socioeconomic status (SES) are
      important factors determining birth outcome. Previous studies have demonstrated
      that, teenagers, and mothers with advanced maternal age (AMA), and Black/Non
      Hispanic race/ethnicity can independently increase the risk for a poor pregnancy
      outcome. Similarly, public insurance has been associated with suboptimal health
      outcomes. The interaction and impact on the risk of a pregnancy resulting in a
      NICU admission has not been studied. Our aim was, to analyze the simultaneous
      interactions of teen/advanced maternal age (AMA), race/ethnicity and
      socioeconomic status on the odds of NICU admission. METHODS: The Consortium of
      Safe Labor Database (subset of n = 167,160 live births) was used to determine
      NICU admission and maternal factors: age, race/ethnicity, insurance, previous c
      section, and gestational age. RESULTS: AMA mothers were more likely than teenaged
      mothers to have a pregnancy result in a NICU admission. Black/Non-Hispanic
      mothers with private insurance had increased odds for NICU admission. This is in
      contrast to the lower odds of NICU admission seen with Hispanic and White/Non
      Hispanic pregnancies with private insurance. CONCLUSIONS: Private insurance is
      protective against a pregnancy resulting in a NICU admission for Hispanic and
      White/Non-Hispanic mothers, but not for Black/Non-Hispanic mothers. The health
      disparity seen between Black and White/Non-Hispanics for the risk of NICU
      admission is most evident among pregnancies covered by private insurance. These
      study findings demonstrate that adverse pregnancy outcomes are mitigated
      differently across race, maternal age, and insurance status.

PMID- 22985093
TI  - Permanent monoparesis in a dog after intramedullary injection of iohexol into the
      lumbar spinal cord.
AB  - Abstract CASE HISTORY: An 8-year-old, spayed, Doberman Pinscher bitch presented
      for assessment of acute hindlimb paresis. CLINICAL FINDINGS: During a lumbar
      myelographic contrast study a small volume of iohexol contrast agent was
      inadvertently injected into the cord parenchyma. After surgical hemilaminectomy
      for an intervertebral disc extrusion at L1-2 the dog recovered use of one
      hindlimb, but had ongoing extensor weakness of the left hindlimb. Left femoral
      nerve function had not returned after 14 months. DIAGNOSIS: EMG findings 14
      months after the incident indicated persistent femoral neuropathy consistent with
      the intramedullary contrast injection at L3-4. CLINICAL RELEVANCE: Inadvertent
      deposition of iohexol into spinal cord parenchyma may be rare, but if it occurs
      it can have long-lasting consequences.

PMID- 22985094
TI  - Selective detection of volatile organic compounds by spectral imaging of
      porphyrin derivatives bound to TiO2 porous films.
AB  - In this work, the carboxylic acid derivatives of a free-base porphyrin,
      5,10,15,20-tetrakis(4-carboxyphenyl)-21H,23H-porphyrin, and 10 of its metal
      derivatives (TCPPs) have been used for optical gas sensing. For this purpose,
      microstructured columnar TiO(2) thin films prepared by GAPVD (glancing angle
      physical vapor deposition) have been used as host materials for the porphyrins as
      they are non-dispersive and porous, allowing their use for UV-visible
      spectroscopy and gas sensing. The chemical binding between the dye molecules and
      the TiO(2) has been studied through infrared spectroscopy, and the obtained
      spectral changes have been found to be compatible with chelating and/or bidentate
      binding modes of the carboxylate groups on the TiO(2) surface. When hosted in the
      film, the UV-visible spectra of the porphyrins featured a blue shift and
      broadening of the Soret band with respect to the solution, which has been
      attributed to the formation of pi-pi aggregates between porphyrin molecules. The
      composite porphyrin/TiO(2) films obtained from each of the 11 porphyrins have
      been exposed to 12 different volatile organic compounds (VOCs), and their
      respective gas-sensitive properties have been analyzed as a function of the
      spectral changes in their Soret band region in the presence of the analytes. The
      set of composite films has shown high selectivity to the analyzed volatile
      compounds. For each analyte, an innovative way of showing the different responses
      has been developed. By means of this procedure, an imagelike recognition pattern
      has been obtained, which allows an easy identification of every compound. The
      kinetics of the exposure to several analytes showed a fast, reversible and
      reproducible response, with response times of a few seconds, which has been
      attributed to both the sensitivity of the porphyrins and the high porosity of the
      TiO(2) films. Also, increasing concentrations of the analytes resulted in an
      increase in the magnitude of the response, indicating that the sensor behavior is
      also concentration-dependent.

PMID- 22985095
TI  - The expression of calretinin and cytokeratins in canine acanthomatous
      ameloblastoma and oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) and canine acanthomatous ameloblastoma (CAA)
      represent two epithelium-derived neoplasms that affect the oral cavity of dogs.
      The expression of cytokeratins (CKs) and calretinin has been previously
      established in the canine tooth bud and odontogenic tumours. The aim of this
      study was to characterize the CK and calretinin expression profile of OSCC in
      comparison to CAA and canine tooth bud tissues. Samples from 15 OSCC and 15 CAA
      cases, as well as 6 tooth buds and 2 normal gingival tissues were examined. OSCC
      CK expression was consistent with the CK expression profile of CAA and canine
      tooth bud tissue. Calretinin was positively expressed in 10 of 15 OSCC cases,
      with 5 cases demonstrating high staining intensity. Only 2 of 15 CAA cases
      demonstrated mild-moderate staining intensity. The statistically significant
      difference in staining pattern and intensity of calretinin in OSCC and CAA can
      help distinguish between these two tumour types. 

PMID- 22985096
TI  - A genome-wide survey for prion-regulated miRNAs associated with cholesterol
      homeostasis.
AB  - BACKGROUND: Prion diseases are neurodegenerative diseases that are characterized
      by the conversion of the cellular prion protein (PrPc) into a pathogenic isoform
      (PrPSc). It is known that neurodegeneration is often accompanied by the
      disturbance of cholesterol homeostasis. We have recently identified a set of
      genes that were upregulated after prion infection of N2a neuronal cells (Bach et
      al., 2009). RESULTS: We have now used ultra-deep sequencing technology to profile
      all microRNAs (miRNA) that could be associated with this effect in these N2a
      cells. Using stringent filters and normalization strategies we identified a small
      set of miRNAs that were up- or downregulated upon prion infection. Using
      bioinformatic tools we predicted whether the downregulated miRNAs could target
      mRNAs that have been previously identified to enhance cholesterol synthesis in
      these cells. Application of this joint profiling approach revealed that nine
      miRNAs potentially target cholesterol-related genes. Four of those miRNAs are
      localized in a miRNA-dense cluster on the mouse X-chromosome. Among these,
      twofold downregulation of mmu-miR-351 and mmu-miR-542-5p was confirmed by qRT
      PCR. The same miRNAs were predicted as putative regulators of the sterol
      regulatory element-binding factor 2 (Srebf2), the low-density lipoprotein
      receptor (Ldlr) or the IPP isomerase. CONCLUSIONS: The results demonstrate that
      joined profiling by ultra-deep sequencing is highly valuable to identify
      candidate miRNAs involved in prion-induced dysregulation of cholesterol
      homeostasis.

PMID- 22985097
TI  - Examining the nature of the comorbidity between pediatric attention
      deficit/hyperactivity disorder and post-traumatic stress disorder.
AB  - OBJECTIVE: This study sought to address the link between attention
      deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD)
      in youth by providing a comprehensive comparison of clinical correlates of ADHD
      subjects with and without PTSD across multiple non-overlapping domains of
      functioning and familial patterns of transmission. METHOD: Participants were 271
      youths with ADHD and 230 controls without ADHD of both sexes along with their
      siblings. Participants completed a large battery of measures designed to assess
      psychiatric comorbidity, psychosocial, educational, and cognitive parameters.
      RESULTS: Post-traumatic stress disorder was significantly higher in ADHD probands
      vs. controls (5.2% vs. 1.7%, chi(2) (1) = 4.36, P = 0.04). Irrespective of the
      comorbidity with PTSD, ADHD subjects had similar ages at onset of ADHD, similar
      type and mean number of ADHD symptoms, and similar ADHD-associated impairments.
      PTSD in ADHD probands was significantly associated with a higher risk of
      psychiatric hospitalization, school impairment, poorer social functioning and
      higher prevalences of mood, conduct disorder, and anxiety disorders. The mean
      onset of PTSD (12.6 years) was significantly later than that of ADHD and comorbid
      disorders (all P < 0.05). Siblings of ADHD and ADHD + PTSD probands had higher
      prevalences of ADHD vs. siblings of controls (35% vs. 18%, z = 4.00, P < 0.001
      and 67% vs. 18%, z = 4.02, P < 0.001 respectively) and siblings of ADHD+PTSD
      probands had a significantly higher prevalence of PTSD compared with the siblings
      of ADHD and control probands (20% vs. 3% and 3%, z = 2.99, P = 0.003 and z =
      2.07, P = 0.04 respectively). CONCLUSION: Findings indicate that the comorbidity
      with PTSD in ADHD leads to greater clinical severity as regards psychiatric
      comorbidity and psychosocial dysfunction. ADHD is equally familial in the
      presence of PTSD in the proband indicating that their co-occurrence is not owing
      to diagnostic error.

PMID- 22985098
TI  - Pilot evaluation of anterior dynamic ultrasound screening for developmental
      dysplasia of the hip in an Australian regional hospital.
AB  - INTRODUCTION: Developmental Dysplasia of the Hip (DDH) is the most common
      notifiable musculoskeletal birth defect in South Australia (SA). Despite routine
      screening by physical examination of the hips in the neonatal period and at 6
      weeks of age, the risk of late diagnosis is increased in rural areas. It is
      assumed this is due to the examining doctors' reduced clinical expertise.
      Introducing Anterior Dynamic Ultrasound (ADUS) has reduced the late detection
      rates in Sweden to almost zero, and may benefit Australian infants in rural areas
      if routine screening was introduced. This study reports on a small implementation
      pilot in a SA regional hospital where volunteer postnatal mothers consented to
      their babies having ADUS examinations. METHODS: The pilot was evaluated by
      collecting results of physical examination, ADUS, and surveying parental
      impressions of the screening test. RESULTS: Hips of 86 infants underwent ADUS
      during the implementation pilot. Parents' perceptions were mainly very positive
      and indicated ADUS was an accessible and acceptable screening test. Of the hips
      scanned, three were found to have maximum movement of the femoral head of >3 mm
      and were deemed to demonstrate increased laxity. Four hips described as loose or
      mobile on clinical examination were found to be within normal limits of maximum
      mobility on ADUS. CONCLUSIONS: This study has demonstrated that a larger scale
      implementation project would be feasible in regional Australia, and would enable
      researchers to better understand how to reduce the late diagnosis rate of DDH in
      rural areas.

PMID- 22985100
TI  - Multidimensional health-transition patterns among a middle-aged and older
      population.
AB  - AIM: Previous studies on health transition have focused on single-dimension
      outcomes and minimally evaluated heterogeneity. This study aimed to explore
      heterogeneous and multidimensional health-transition patterns on comorbidity,
      frailty and disability while examining the factors predicting different patterns
      of health transition. METHODS: This study drew on data from a nationwide and
      longitudinally-followed sample of 5131 Taiwanese aged 50 years and older who were
      interviewed in 1996, 1999, 2003 and 2007. Latent class analysis (LCA) and
      multinomial logistic regression were applied to identify health-transition
      patterns and their predictors. RESULTS: We identified six health-transition
      classes by applying LCA, including "persistently healthy", "well-managed
      comorbidity", "originally comorbid and gradually deteriorating to disability",
      "deteriorating gradually and died in late stage of the follow-up period",
      "deteriorating and died in middle stage of the follow-up period", and "originally
      comorbid and died in early stage of the follow-up period". Using the "well
      managed comorbidity" class as the reference group, men had higher probabilities
      of being in the categories of dying in the follow-up period, but a lower risk of
      deteriorating to disability. Younger baseline age, higher education, having
      social engagement and non-smoking were predictors of "persistently healthy" and
      were associated with a lower risk of deteriorating to disability and death.
      Having a spouse and health examinations were associated with a lower risk of
      death, and also a lower probability of "persistently healthy". CONCLUSIONS:
      Heterogeneous and multidimensional health-transition patterns exist in middle
      aged and older populations. Several factors might have an effect on health
      transition patterns.

PMID- 22985101
TI  - Structural characterization of polyketides using high mass accuracy tandem mass
      spectrometry.
AB  - The tandem mass spectrometry techniques electron-induced dissociation (EID) and
      collision-activated dissociation (CAD) have been compared as tools for providing
      detailed structural information of polyketides. Polyketides are an important
      class of natural products that account for a significant proportion of the drugs
      currently in clinical use. Three polyketide natural products, namely erythromycin
      A, lasalocid A, and iso-lasalocid A, were subjected to both CAD and EID, and
      their fragment ions were assigned with sub-part-per-million accuracy. The number
      of fragment ions detected through EID was much greater than for CAD, leading to a
      greater amount of structural information obtained for each polyketide, albeit
      with a decreased signal-to-noise ratio. The effect of different bound cations on
      the fragment pattern of the isomers lasalocid A and iso-lasalocid A was studied,
      with CAD and EID performed on the [M + H](+), [M + Na](+), [M + Li](+), and [M +
      NH(4)](+) precursor ions. The lithiated species were found to produce the
      greatest degree of fragmentation and enabled detailed structural information on
      the isomers to be obtained. Multistage mass spectrometry (MS(3)) experiments,
      combining CAD and EID, could also be performed on the lithiated species,
      generating new fragment information which enables the two isomers to be
      distinguished. Combining CAD and EID for the structural characterization of
      polyketides will therefore be a useful tool for identifying and characterizing
      unknown polyketides and their biosynthetic intermediates.

PMID- 22985102
TI  - Single hydration of the peptide bond: the case of the Vince lactam.
AB  - 2-Azabicyclo[2.2.1]hept-5-en-3-one (ABH or Vince lactam) and its monohydrated
      complex (ABH...H(2)O) have been observed in a supersonic jet by Fourier transform
      microwave spectroscopy. ABH is broadly used in the synthesis of therapeutic
      drugs, whereas the ABH...H(2)O system offers a simple model to explain the
      conformational preferences of water linked to a constrained peptidic bond. A
      single predominant form of the Vince lactam and its singly hydrated complex have
      been detected, determining the rotational constants, centrifugal distortion
      constants, and nuclear quadrupole coupling tensor. The monohydrated complex is
      stabilized by two hydrogen bonds (C?O...H-O and N-H...O) closing a six-membered
      ring. The complexation energy has been estimated to be ~10 kJ mol(-1) from
      experimental results. In addition, the observed structure in the gas phase has
      been compared with solid-phase diffraction data. The structural parameters and
      binding energies of ABH...H(2)O have also been compared with similar molecules
      containing peptide bonds. Ab initio (MP2) and density functional (M06-2X and
      B3LYP) methods have supported the experimental work, describing the rotational
      parameters and conformational landscape of the title compound and its singly
      hydrated complex.

PMID- 22985104
TI  - Simultaneous thalamic and posterior subthalamic electrode insertion with single
      deep brain stimulation electrode for essential tremor.
AB  - OBJECTIVES: The optimal target location of deep brain stimulation (DBS) is the
      subject of some controversy. We implanted electrodes that could stimulate both
      posterior subthalamic area (PSA) and ventralis intermedius nucleus of thalamus
      (Vim), and examined the benefits of bilateral DBS of Vim, PSA, and Vim + PSA in
      patients with essential tremor (ET). MATERIALS AND METHODS: Electrodes were
      inserted into the Vim and PSA in ten hemispheres of five consecutive patients.
      All patients were assessed for action tremor, including postural and kinetic
      tremors, both preoperatively and at six months and one year postoperatively.
      RESULTS:  The preoperative mean postural tremor score was 1.9 (range 1.0-2.5) and
      kinetic tremor score was 2.6 (range 2.0-3.0). One year after surgery, these
      scores had decreased significantly to 0.1 (range 0.0-1.0) and 0.6 (range 0.0
      1.5), respectively. The postural and kinetic tremor scores at six-months and one
      year post-surgery were similar for Vim, PSA, and Vim + PSA stimulation.
      CONCLUSIONS:  We were able to identify the optimal electrode placement site for
      each patient based on his or her individualized response to the stimulation.
      Overall, there was no statistically significant difference among the DBS sites in
      terms of the benefits afforded by the stimulation. We propose that our technique
      may be a useful surgical method to treat ET.

PMID- 22985105
TI  - Where deer roam: chronic yet acute site exposures preclude ecological risk
      assessment.
AB  - Global positioning system (GPS) technology has made possible the detailed
      tracking of the spatial movements of wildlife. Using GPS tracking collars placed
      on female white-tailed deer (Odocoileus virginianus) over a protracted period, we
      illustrate that this species is spatially irrelevant for consideration in
      ecological risk assessments (ERAs) for commonly assessed contaminated sites.
      Specifically, deer movements do not allow for a sufficiency of chemical exposures
      to occur such that toxicological endpoints would be triggered. Deer are spatially
      irrelevant not only because their home ranges and overall utilized areas dwarf
      prototypical hazardous waste sites. They are also inappropriate for assessment
      because they only minimally contact reasonably sized preferred locations, this
      while demonstrating a confounding high degree of site affinity for them. Our
      spatial movements analysis suggests that deer introduce the ERA novelty of a
      species displaying elements of both chronic and acute site exposure. We further
      suggest that other large commonly assessed high-profile mammals could also be
      found to be spatially irrelevant for ERAs were they to submit to the GPS tracking
      and subsequent data analysis we performed for the deer. Recognizing that certain
      receptors need not be considered in ERAs can help to simplify the ERA process.

PMID- 22985103
TI  - Perspectives on care and communication involving incurably ill Turkish and
      Moroccan patients, relatives and professionals: a systematic literature review.
AB  - BACKGROUND: Our aim was to obtain a clearer picture of the relevant care
      experiences and care perceptions of incurably ill Turkish and Moroccan patients,
      their relatives and professional care providers, as well as of communication and
      decision-making patterns at the end of life. The ultimate objective is to improve
      palliative care for Turkish and Moroccan immigrants in the Netherlands, by taking
      account of socio-cultural factors in the guidelines for palliative care. METHODS:
      A systematic literature review was undertaken. The data sources were seventeen
      national and international literature databases, four Dutch journals dedicated to
      palliative care and 37 websites of relevant national and international
      organizations. All the references found were checked to see whether they met the
      structured inclusion criteria. Inclusion was limited to publications dealing with
      primary empirical research on the relationship between socio-cultural factors and
      the health or care situation of Turkish or Moroccan patients with an oncological
      or incurable disease. The selection was made by first reading the titles and
      abstracts and subsequently the full texts. The process of deciding which studies
      to include was carried out by two reviewers independently. A generic appraisal
      instrument was applied to assess the methodological quality. RESULTS: Fifty-seven
      studies were found that reported findings for the countries of origin (mainly
      Turkey) and the immigrant host countries (mainly the Netherlands). The central
      themes were experiences and perceptions of family care, professional care, end-of
      life care and communication. Family care is considered a duty, even when such
      care becomes a severe burden for the main female family caregiver in particular.
      Professional hospital care is preferred by many of the patients and relatives
      because they are looking for a cure and security. End-of-life care is strongly
      influenced by the continuing hope for recovery. Relatives are often quite
      influential in end-of-life decisions, such as the decision to withdraw or
      withhold treatments. The diagnosis, prognosis and end-of-life decisions are
      seldom discussed with the patient, and communication about pain and mental
      problems is often limited. Language barriers and the dominance of the family may
      exacerbate communication problems. CONCLUSIONS: This review confirms the view
      that family members of patients with a Turkish or Moroccan background have a
      central role in care, communication and decision making at the end of life. This,
      in combination with their continuing hope for the patient's recovery may inhibit
      open communication between patients, relatives and professionals as partners in
      palliative care. This implies that organizations and professionals involved in
      palliative care should take patients' socio-cultural characteristics into account
      and incorporate cultural sensitivity into care standards and care practices.

PMID- 22985106
TI  - Synthesis and assembly of colloidal particles with sticky dimples.
AB  - The preparation of anisotropic colloidal particles by a simple yet versatile
      temperature-controlled swelling process is described. The resulting polymeric
      particles feature a surface dimple, the size and shape of which were determined
      by the amount of oil captured in particles and the interfacial tension between
      the three phases: polystyrene (PS), decane, and the suspending medium. Following
      the removal of free or physically adsorbed surfactant from the swollen particles,
      hydrophobic dimples were produced upon evaporation of the oil phase. We
      demonstrate the spontaneous assembly of these 'dimpled particles' into dumbbell
      shapes or trimers through a site-selective hydrophobic interaction.

PMID- 22985107
TI  - Tackling indifference--clowning, dementia, and the articulation of a sensitive
      body.
AB  - In this auto-ethnographic study, I focus on a special form of clowning for people
      at an advanced stage of dementia. The miMakkus clown is presented as a specialist
      in contact with people with whom communication is no longer possible by the usual
      (linguistic, cognitive) means. I illustrate how the miMakkus clown tries to reach
      people with dementia, focusing specifically on the role of the sensitive body as
      an instrument for attunement. As I demonstrate, in their contact, the clown and
      the person with dementia are involved in a process of mutual articulation.

PMID- 22985108
TI  - Cyanobacteria blooms: Maya peoples between the politics of risk and the threat of
      disaster.
AB  - In October of 2009 an outbreak of cyanobacteria in Lake Atitlan, Guatemala gained
      international attention and global news coverage with interests coming from
      environmentalists, microbiologists, and local health agencies. A significantly
      less well-known aspect of the crisis was the perceptions and predicaments of Maya
      (indigenous) peoples for whom the lake is the primary source of life and
      livelihood. This research examines the communication of the public health risk of
      cyanobacteria to Maya peoples. Using an "ethnography of risk communication"
      approach, this work traces the circulation of the science of cyanobacteria and
      the construction of risk from government and public health translations through
      media transmissions to local Maya interpretations. The findings demonstrate how
      government and institutional translations (and media transmissions) of the
      science of cyanobacteria not only unwittingly produced misunderstandings about
      the health dangers but indirectly associated blame for the outbreak with
      indigenous peoples, calling into question their way of life.

PMID- 22985109
TI  - A goat's head on a sheep's body? Manufacturing good practices for Tibetan
      medicine.
AB  - The production of Tibetan pharmaceuticals underwent a far-reaching transformation
      over the past decade. The introduction of good manufacturing practices (GMP)
      marked the beginning of rapid industrialization: new factories were built, and
      the companies re-oriented themselves to the requirements of the market. While
      officially regarded a great success, many doctors and pharmacists see GMP as
      fundamentally incompatible with traditional production methods and notions of
      quality. In this article, I address this incompatibility and examine where and
      how it affects the actual practice of producing medicines. While the problem
      exists, I argue that it does not stem from conflicting epistemologies but rather
      from the side effects of a quick and forced implementation, which often
      contradicts the spirit and letter of the regulations themselves. The case sheds
      new light on the way in which ideas about quality and safety, forged in the
      global arena, are locally recontextualized.

PMID- 22985110
TI  - Patterns of persistence amidst medical pluralism: pathways toward cure in the
      southern Peruvian Andes.
AB  - When mental illness and related conditions strike among the Quechua-speaking
      peasant population of southern Peru, they open wide the question of who is best
      placed to offer the healing that families seek for their afflicted relative.
      Biomedical doctors and the traditional healers known as yachaqs are the two most
      commonly consulted sources of help. Yet most families show different patterns of
      persistence with each; they frequently give up on biomedical assistance after the
      initial intervention but continue to consult a succession of yachaqs over
      considerable periods of time, even if the former has had some limited success and
      the latter virtually none. I draw on ethnographic fieldwork to show that
      explanations based on inaccessibility, cultural incongruence between patient and
      clinician, or stigma are ultimately inadequate; rather, it is necessary to delve
      into fundamental differences in how the two fields of healing are conceptualized
      by those negotiating them.

PMID- 22985113
TI  - Directed evolution: tailoring biocatalysts for industrial applications.
AB  - Current challenges and promises of white biotechnology encourage protein
      engineers to use a directed evolution approach to generate novel and useful
      biocatalysts for various sets of applications. Different methods of enzyme
      engineering have been used in the past in an attempt to produce enzymes with
      improved functions and properties. Recent advancement in the field of random
      mutagenesis, screening, selection and computational design increased the
      versatility and the rapid development of enzymes under strong selection pressure
      with directed evolution experiments. Techniques of directed evolution improve
      enzymes fitness without understanding them in great detail and clearly
      demonstrate its future role in adapting enzymes for use in industry. Despite
      significant advances to date regarding biocatalyst improvement, there still
      remains a need to improve mutagenesis strategies and development of easy
      screening and selection tools without significant human intervention. This review
      covers fundamental and major development of directed evolution techniques, and
      highlights the advances in mutagenesis, screening and selection methods with
      examples of enzymes developed by using these approaches. Several commonly used
      methods for creating molecular diversity with their advantages and disadvantages
      including some recently used strategies are also discussed. 

PMID- 22985112
TI  - Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat
      kinase 2 (LRRK2) small molecule inhibitors.
AB  - There is a high demand for potent, selective, and brain-penetrant small molecule
      inhibitors of leucine-rich repeat kinase 2 (LRRK2) to test whether inhibition of
      LRRK2 kinase activity is a potentially viable treatment option for Parkinson's
      disease patients. Herein we disclose the use of property and structure-based drug
      design for the optimization of highly ligand efficient aminopyrimidine lead
      compounds. High throughput in vivo rodent cassette pharmacokinetic studies
      enabled rapid validation of in vitro-in vivo correlations. Guided by this data,
      optimal design parameters were established. Effective incorporation of these
      guidelines into our molecular design process resulted in the discovery of small
      molecule inhibitors such as GNE-7915 (18) and 19, which possess an ideal balance
      of LRRK2 cellular potency, broad kinase selectivity, metabolic stability, and
      brain penetration across multiple species. Advancement of GNE-7915 into rodent
      and higher species toxicity studies enabled risk assessment for early
      development.

PMID- 22985114
TI  - A social exchange-based model of the antecedents of workplace exclusion.
AB  - We conducted 2 studies of coworker dyads to test a theoretical model exploring
      why and under what circumstances employees are the targets of workplace
      exclusion. Adopting a victim precipitation perspective, we integrate
      belongingness and social exchange theories to propose that employees who display
      workplace incivility are distrusted and therefore are targets of workplace
      exclusion. Highlighting the importance of the context of the perpetrator-target
      relationship, we also find support for the postulation that this mediated
      relationship is strengthened when the target employee is perceived to be a weak
      exchange partner and is attenuated when he or she is viewed as a valuable
      exchange partner. Theoretical and practical implications are discussed.

PMID- 22985115
TI  - Behavioral integrity for safety, priority of safety, psychological safety, and
      patient safety: a team-level study.
AB  - This article clarifies how leader behavioral integrity for safety helps solve
      follower's double bind between adhering to safety protocols and speaking up about
      mistakes against protocols. Path modeling of survey data in 54 nursing teams
      showed that head nurse behavioral integrity for safety positively relates to both
      team priority of safety and psychological safety. In turn, team priority of
      safety and team psychological safety were, respectively, negatively and
      positively related with the number of treatment errors that were reported to head
      nurses. We further demonstrated an interaction effect between team priority of
      safety and psychological safety on reported errors such that the relationship
      between team priority of safety and the number of errors was stronger for higher
      levels of team psychological safety. Finally, we showed that both team priority
      of safety and team psychological safety mediated the relationship between leader
      behavioral integrity for safety and reported treatment errors. These results
      suggest that although adhering to safety protocols and admitting mistakes against
      those protocols show opposite relations to reported treatment errors, both are
      important to improving patient safety and both are fostered by leaders who walk
      their safety talk.

PMID- 22985116
TI  - Who gives? Multilevel effects of gender and ethnicity on workplace charitable
      giving.
AB  - Research on diversity in organizations has largely focused on the implications of
      gender and ethnic differences for performance, to the exclusion of other
      outcomes. We propose that gender and ethnic differences also have implications
      for workplace charitable giving, an important aspect of corporate social
      responsibility. Drawing from social role theory, we hypothesize and find that
      gender has consistent effects across levels of analysis; women donate more money
      to workplace charity than do men, and the percentage of women in a work unit is
      positively related to workplace charity, at least among men. Alternatively and
      consistent with social exchange theory, we hypothesize and find that ethnicity
      has opposing effects across levels of analysis; ethnic minorities donate less
      money to workplace charity than do Whites, but the percentage of minorities in a
      work unit is positively related to workplace charity, particularly among
      minorities. The findings provide a novel perspective on the consequences of
      gender and ethnic diversity in organizations and highlight synergies between
      organizational efforts to increase diversity and to build a reputation for
      corporate social responsibility.

PMID- 22985117
TI  - Leader-member exchange (LMX) and culture: a meta-analysis of correlates of LMX
      across 23 countries.
AB  - This study extends leader-member exchange (LMX) research by meta-analyzing the
      role of national culture in moderating relationships between LMX and its
      correlates. Results based on 282 independent samples (N = 68,587) from 23
      countries and controlling for extreme response style differences indicate that
      (a) relationships of LMX with organizational citizenship behavior, justice
      perceptions, job satisfaction, turnover intentions, and leader trust are stronger
      in horizontal-individualistic (e.g., Western) contexts than in vertical
      collectivistic (e.g., Asian) contexts; and (b) national culture does not affect
      relationships of LMX with task performance, organizational commitment, and
      transformational leadership. These findings highlight that although members are
      universally sensitive to how their leaders treat them, members' responses in
      Asian contexts may also be influenced by collective interests and role-based
      obligations.

PMID- 22985118
TI  - Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary
      thyroid cancer and the prognosis and implications for surgical management.
AB  - BACKGROUND: To compare outcomes for patients with recurrent or persistent
      papillary thyroid cancer (PTC) who had metastatic tumors that were
      fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative,
      and to determine whether the FDG-PET scan findings changed the outcome of medical
      and surgical management. METHODS: From a prospective thyroid cancer database, we
      retrospectively identified patients with recurrent or persistent PTC and reviewed
      data on demographics, initial stage, location and extent of persistent or
      recurrent disease, clinical management, disease-free survival and outcome. We
      further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT
      scan and whole-body radioactive iodine scans and categorized them by whether they
      had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The
      medical and surgical treatments and outcome of these patients were compared.
      RESULTS: Between 1984 and 2008, 41 of 141 patients who had recurrent or
      persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22
      patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative
      lesions, and two had indeterminate lesions. Most PET-positive lesions were
      located in the neck (55%). Patients who had a PET-positive lesion had a
      significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher
      thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22
      vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who
      underwent surgical resection of their PET-positive lesions, loco-regional control
      was obtained without evidence of residual disease. CONCLUSION: Patients with
      recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis.
      In some patients loco-regional control can be obtained without evidence of
      residual disease by reoperation if the lesion is localized in the neck or
      mediastinum.

PMID- 22985119
TI  - Characterization of mesoporous thin films by specular reflectance porosimetry.
AB  - The pore size distribution of mesoporous thin films is herein investigated
      through a reliable and versatile technique coined specular reflectance
      porosimetry. This method is based on the analysis of the gradual shift of the
      optical response of a porous slab measured in quasi-normal reflection mode that
      occurs as the vapor pressure of a volatile liquid varies in a closed chamber. The
      fitting of the spectra collected at each vapor pressure is employed to calculate
      the volume of solvent contained in the interstitial sites and thus to obtain
      adsorption-desorption isotherms from which the pore size distribution and
      internal and external specific surface areas are extracted. This technique
      requires only a microscope operating in the visible range attached to a
      spectrophotometre. Its suitability to analyze films deposited onto arbitrary
      substrates, one of the main limitations of currently employed ellipsometric
      porosimetry and quartz balance techniques, is demonstrated. Two standard
      mesoporous materials, supramolecularly templated mesostructured films and packed
      nanoparticle layers, are employed to prove the concept proposed herein.

PMID- 22985120
TI  - An imaging method for oxygen distribution, respiration and photosynthesis at a
      microscopic level of resolution.
AB  - Biological samples are far from homogeneous, with complex compartmentation being
      the norm. Major physiological processes such as respiration do not therefore
      occur in a uniform manner within most tissues, and it is currently not possible
      to image its gradients in living plant tissues. A compact fluorescence
      ratiometric-based device is presented here, consisting of an oxygen-sensitive
      foil and a USB (universal serial bus) microscope. The sensor foil is placed on
      the sample surface and, based on the localized change in fluorescence signal over
      time, information about the oxygen consumption (respiration) or evolution
      (photosynthesis) can be obtained. Using this imaging technique, it was possible
      to demonstrate the spatial pattern of oxygen production and consumption at a c.
      20-MUm level of resolution, and their visualization in the rhizosphere, stem and
      leaf, and within the developing seed. The oxygen mapping highlighted the vascular
      tissues as the major stem sink for oxygen. In the leaf, the level of spatial
      resolution was sufficient to visualize the gas exchange in individual stomata. We
      conclude that the novel sensor set-up can visualize gradients in oxygen-consuming
      and producing processes, thereby facilitating the study of the spatial dynamics
      of respiration and photosynthesis in heterogeneous plant tissues.

PMID- 22985121
TI  - Adenoviruses - from pathogens to therapeutics: a report on the 10th International
      Adenovirus Meeting.

PMID- 22985122
TI  - Interview with Brian Kennedy, Ph.D. Interview by Vicki Glaser.
AB  - Editor's note: The interview series in Rejuvenation Research is a unique and, I
      believe, highly valuable feature of the journal, giving readers insights into the
      thinking and motivation of some of the most influential movers and shakers in the
      many disciplines--not only scientific but also political, sociological, ethical,
      and more--that impinge on the crusade to defeat aging. Dissemination of the views
      and insights of such people is essential to the process of communication between
      the field of biomedical gerontology and the many constituencies that will be
      affected by progress against aging--a dialogue that, as I and others have noted
      recently, is essential if we are to develop effective interventions against aging
      with all possible speed.

PMID- 22985123
TI  - The evolution of intraventricular vortex during ejection studied by using vector
      flow mapping.
AB  - AIMS: The purpose of this study was to assess the evolution of intraventricular
      vortex during left ventricular (LV) ejection. METHODS: Vector flow mapping was
      performed in 51 patients with coronary artery disease and LV ejection fraction
      (EF) >50%, 70 patients with EF <50% (13 with coronary artery disease and 57 with
      dilated cardiomyopathy), and 62 healthy volunteers. RESULTS: In normals and
      patients with EF >50%, the intraventricular vortex dissipated quickly during
      early ejection. In patients with EF <50%, the vortex stayed mainly at apex and
      persisted for a significantly longer time. The evolution of vortex during
      ejection was significantly correlated with QRS width, EF, fractional shortening,
      LV outflow velocity time integral, wall motion score index (WMSI), LV dimensions,
      left atrial diameter, and diastolic mitral annular velocities. LV end-diastolic
      short diameter and WMSI were the independent determinants of the duration of
      vortex (R(2) = 0.482, P < 0.001). End-systolic short diameter and apical WMSI
      were the independent determinants of duration of vortex corrected for ejection
      time (R(2) = 0.565, P < 0.001). End-systolic short diameter was the independent
      determinant of percentage change in vortex area during early ejection (R(2) =
      0.355, P < 0.001). End-systolic short diameter and ejection time were the
      independent determinants of percentage change in vortex flow volume (R(2) =
      0.415, P < 0.001). CONCLUSIONS: In patients with LV systolic dysfunction, the
      vortex persists during ejection and stays mainly at apex. The vortex evolution
      during ejection is closely associated with LV dimensions and functions.

PMID- 22985124
TI  - Far-field imaging for direct visualization of light interferences in GaAs
      nanowires.
AB  - The optical and electrical characterization of nanostructures is crucial for all
      applications in nanophotonics. Particularly important is the knowledge of the
      optical near-field distribution for the design of future photonic devices. A
      common method to determine optical near-fields is scanning near-field optical
      microscopy (SNOM) which is slow and might distort the near-field. Here, we
      present a technique that permits sensing indirectly the infrared near-field in
      GaAs nanowires via its second-harmonic generated (SHG) signal utilizing a
      nonscanning far-field microscope. Using an incident light of 820 nm and the very
      short mean free path (16 nm) of the SHG signal in GaAs, we demonstrate a fast
      surface sensitive imaging technique without using a SNOM. We observe periodic
      intensity patterns in untapered and tapered GaAs nanowires that are attributed to
      the fundamental mode of a guided wave modulating the Mie-scattered incident
      light. The periodicity of the interferences permits to accurately determine the
      nanowires' radii by just using optical microscopy, i.e., without requiring
      electron microscopy.

PMID- 22985126
TI  - Has increased clinical experience with methotrexate reduced the direct costs of
      medical management of ectopic pregnancy compared to surgery?
AB  - BACKGROUND: There is a debate about the cost-efficiency of methotrexate for the
      management of ectopic pregnancy (EP), especially for patients presenting with
      serum human chorionic gonadotrophin levels of >1500 IU/L. We hypothesised that
      further experience with methotrexate, and increased use of guideline-based
      protocols, has reduced the direct costs of management with methotrexate. METHODS:
      We conducted a retrospective cost analysis on women treated for EP in a large UK
      teaching hospital to (1) investigate whether the cost of medical management is
      less expensive than surgical management for those patients eligible for both
      treatments and (2) to compare the cost of medical management for women with hCG
      concentrations 1500-3000 IU/L against those with similar hCG concentrations that
      elected for surgery. Three distinct treatment groups were identified: (1) those
      who had initial medical management with methotrexate, (2) those who were eligible
      for initial medical management but chose surgery ('elected' surgery) and (3)
      those who initially 'required' surgery and did not meet the eligibility criteria
      for methotrexate. We calculated the costs from the point of view of the National
      Health Service (NHS) in the UK. We summarised the cost per study group using the
      mean, standard deviation, median and range and, to account for the skewed nature
      of the data, we calculated 95% confidence intervals for differential costs using
      the nonparametric bootstrap method. RESULTS: Methotrexate was L1179 (CI 819-1550)
      per patient cheaper than surgery but there were no significant savings with
      methotrexate in women with hCG >1500 IU/L due to treatment failures. CONCLUSIONS:
      Our data support an ongoing unmet economic need for better medical treatments for
      EP with hCG >1500 IU/L.

PMID- 22985125
TI  - Transcriptomic analysis of the red seaweed Laurencia dendroidea (Florideophyceae,
      Rhodophyta) and its microbiome.
AB  - BACKGROUND: Seaweeds of the Laurencia genus have a broad geographic distribution
      and are largely recognized as important sources of secondary metabolites, mainly
      halogenated compounds exhibiting diverse potential pharmacological activities and
      relevant ecological role as anti-epibiosis. Host-microbe interaction is a driving
      force for co-evolution in the marine environment, but molecular studies of
      seaweed-associated microbial communities are still rare. Despite the large amount
      of research describing the chemical compositions of Laurencia species, the
      genetic knowledge regarding this genus is currently restricted to taxonomic
      markers and general genome features. In this work we analyze the transcriptomic
      profile of L. dendroidea J. Agardh, unveil the genes involved on the biosynthesis
      of terpenoid compounds in this seaweed and explore the interactions between this
      host and its associated microbiome. RESULTS: A total of 6 transcriptomes were
      obtained from specimens of L. dendroidea sampled in three different coastal
      locations of the Rio de Janeiro state. Functional annotations revealed
      predominantly basic cellular metabolic pathways. Bacteria was the dominant active
      group in the microbiome of L. dendroidea, standing out nitrogen fixing
      Cyanobacteria and aerobic heterotrophic Proteobacteria. The analysis of the
      relative contribution of each domain highlighted bacterial features related to
      glycolysis, lipid and polysaccharide breakdown, and also recognition of seaweed
      surface and establishment of biofilm. Eukaryotic transcripts, on the other hand,
      were associated with photosynthesis, synthesis of carbohydrate reserves, and
      defense mechanisms, including the biosynthesis of terpenoids through the
      mevalonate-independent pathway. CONCLUSIONS: This work describes the first
      transcriptomic profile of the red seaweed L. dendroidea, increasing the knowledge
      about ESTs from the Florideophyceae algal class. Our data suggest an important
      role for L. dendroidea in the primary production of the holobiont and the role of
      Bacteria as consumers of organic matter and possibly also as nitrogen source.
      Furthermore, this seaweed expressed sequences related to terpene biosynthesis,
      including the complete mevalonate-independent pathway, which offers new
      possibilities for biotechnological applications using secondary metabolites from
      L. dendroidea.

PMID- 22985127
TI  - Evolution of CT imaging features of carotid atherosclerotic plaques in a 1-year
      prospective cohort study.
AB  - PURPOSE: The purpose of this study was to identify imaging markers and clinical
      risk factors that significantly predict the evolution of computed tomography (CT)
      imaging features of carotid artery atherosclerotic disease over a 1-year period.
      METHODS: Our prospective study involved 120 consecutive patients undergoing
      emergent CT evaluation for symptoms of acute stroke. These patients were asked to
      consent to a follow-up CT exam in 1 year. To evaluate for atherosclerotic plaque,
      both at baseline and on follow-up, we employed a comprehensive computed
      tomography angiography (CTA) protocol that captured the carotid, vertebral,
      aortic, and coronary arteries. To further evaluate carotid artery plaque
      components, we used an automated classifier computer algorithm that distinguishes
      among the histological components of the carotid artery wall (lipids, calcium,
      fibrous tissue) based on appropriate thresholds of CT density. Baseline values of
      carotid imaging features and clinical variables were assessed for their ability
      to significantly predict changes in these imaging features over 1 year. RESULTS:
      Of these 120 consecutive patients, 17 received both a baseline and a follow-up
      CTA exam. Wall volume increased more when the largest lipid cluster was located
      close to the lumen (coefficient -7.61, -13.83 to -1.40, P = .016). The volume of
      lipid increased with age (coefficient .36, .21 to .50, P = .000), in smokers
      (coefficient 8.89, 6.82 to 10.95, P = .000) and when fewer lipid clusters were
      present at baseline (coefficient -0.11, -0.17 to -.04, P = .001). The volume of
      calcium increased with greater volume of lipid at baseline (coefficient .35, .02
      to .68, P = .035) and in patients on statins (coefficient 4.79, 1.73 to 7.86, P =
      .002). CONCLUSIONS: There are a number of imaging markers and risk factors that
      significantly predict the evolution of CT imaging features of carotid artery
      atherosclerotic disease over a 1-year period.

PMID- 22985128
TI  - Efficacy and effectiveness of percutaneous tibial nerve stimulation in the
      treatment of pelvic organ disorders: a systematic review.
AB  - OBJECTIVE: This systematic review aimed to determine the efficacy and
      effectiveness of percutaneous tibial nerve stimulation (PTNS) on symptoms of
      overactive bladder (OAB) and pelvic organ disorders, pain, adverse events (AEs),
      and quality of life (QoL). METHODS: A literature search was performed in
      September 2011 in the databases MEDLINE, CINAHL, and EMBASE. Hand searching of
      references was conducted. Only randomized controlled trials (RCTs) and controlled
      clinical trials (CCTs) with adult patients were included. RESULTS: Seven studies
      met the eligibility criteria. Five RCTs indicated improvement (range 36.7-80%) on
      OAB symptoms, frequency, urgency, nocturia, and incontinence. One CCT reported
      improvement (mean 15.7) in 53% of the subjects on fecal incontinence (FI)
      symptoms on an FI Questionnaire (range 0-20). One RCT showed more than 50%
      improvement on pain (40%) and symptom scores (66.6%) in chronic pelvic pain
      (CPP). Limitations are the small amount, overall low quality, and variety in
      outcome measures of included studies. Only minor AEs were reported. No meta
      analysis was performed as a consequence of heterogeneous data. CONCLUSIONS: This
      systematic review provides evidence for the efficacy of PTNS on symptoms, pain,
      and QoL measures of OAB, FI and category IIIB CP/CPP. Evidence of effectiveness
      was found on symptoms and QoL for OAB. The total amount of seven included
      studies, from which even the most favorable study has some potential bias, is too
      small to draw firm conclusions. Independent high quality RCTs are necessary to
      confirm and delineate the range of therapeutic effects of PTNS in this region.
      PTNS is a safe intervention.

PMID- 22985129
TI  - Prospective comparison of clinical prognostic scores in elder patients with a
      pulmonary embolism.
AB  - BACKGROUND: The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity
      Index (PESI) and its simplified version (sPESI) are well-known clinical
      prognostic scores for a pulmonary embolism (PE). OBJECTIVES: To compare the
      prognostic performance of these scores in elderly patients with a PE. PATIENTS
      AND METHODS: In a multicenter Swiss cohort of elderly patients with venous
      thromboembolism, we prospectively studied 449 patients aged >= 65 years with a
      symptomatic PE. The outcome was 30-day overall mortality. We dichotomized
      patients as low vs. higher risk in all three scores using the following
      thresholds: GPS scores <= 2 vs. > 2, PESI risk classes I-II vs. III-V and sPESI
      scores 0 vs. >= 1. We compared 30-day mortality in low- vs. higher-risk patients
      and the areas under the receiver-operating characteristic curve (ROC). RESULTS:
      Overall, 3.8% of patients (17/449) died within 30 days. The GPS classified a
      greater proportion of patients as low risk (92% [413/449]) than the PESI (36.3%
      [163/449]) and the sPESI (39.6% [178/449]) (P < 0.001 for each comparison). Low
      risk patients based on the sPESI had a mortality of 0% (95% confidence interval
      [CI] 0-2.1%) compared with 0.6% (95% CI 0-3.4%) for low-risk patients based on
      the PESI and 3.4% (95% CI 1.9-5.6%) for low-risk patients based on the GPS. The
      areas under the ROC curves were 0.77 (95% CI 0.72-0.81), 0.76 (95% CI 0.72-0.80)
      and 0.71 (95% CI 0.66-0.75), respectively (P = 0.47). CONCLUSIONS: In this cohort
      of elderly patients with PE, the GPS identified a higher proportion of patients
      as low risk but the PESI and sPESI were more accurate in predicting mortality.

PMID- 22985130
TI  - Multifunctional sample preparation kit and on-chip quantitative nucleic acid
      sequence-based amplification tests for microbial detection.
AB  - This study reports a quantitative nucleic acid sequence-based amplification (Q
      NASBA) microfluidic platform composed of a membrane-based sampling module, a
      sample preparation cassette, and a 24-channel Q-NASBA chip for environmental
      investigations on aquatic microorganisms. This low-cost and highly efficient
      sampling module, having seamless connection with the subsequent steps of sample
      preparation and quantitative detection, is designed for the collection of
      microbial communities from aquatic environments. Eight kinds of commercial
      membrane filters are relevantly analyzed using Saccharomyces cerevisiae,
      Escherichia coli, and Staphylococcus aureus as model microorganisms. After the
      microorganisms are concentrated on the membrane filters, the retentate can be
      easily conserved in a transport medium (TM) buffer and sent to a remote
      laboratory. A Q-NASBA-oriented sample preparation cassette is originally designed
      to extract DNA/RNA molecules directly from the captured cells on the membranes.
      Sequentially, the extract is analyzed within Q-NASBA chips that are compatible
      with common microplate readers in laboratories. Particularly, a novel analytical
      algorithmic method is developed for simple but robust on-chip Q-NASBA assays. The
      reported multifunctional microfluidic system could detect a few microorganisms
      quantitatively and simultaneously. Further research should be conducted to
      simplify and standardize ecological investigations on aquatic environments.

PMID- 22985131
TI  - Adherence to ARV medication in Romanian young adults: self-reported behaviour and
      psychological barriers.
AB  - Adherence to antiretroviral (ARV) treatment during adolescence and young
      adulthood is a significant clinical issue for the current management of the
      HIV/AIDS epidemic in Romania. Understanding patients' own perceptions of their
      adherence behaviours and related psychological barriers is instrumental for
      developing robust interventions, and developing psychometrically sound
      instruments is essential for measuring adherence in this population. We adapted
      to Romanian an internationally validated questionnaire for the evaluation of ARV
      treatment adherence. We subsequently conducted a cross-sectional survey to
      examine its psychometric properties and investigate the relations between self
      reported aspects of adherence and established indicators of adherence and health
      status: Pill count, doctor's assessment of patient's adherence and viral load.
      Results suggest that low self-reported adherence is particularly associated with
      experiencing side effects and emotional distress, as well as perceptions of high
      treatment difficulty and time demands, low self-efficacy, low treatment efficacy
      and low treatment satisfaction. Perceptions of improvements in health status were
      overall associated with increased adherence, but feeling good physically
      sometimes preceded non-adherence behaviours. The questionnaire proved
      psychometrically sound according to classical test theory criteria (e.g.,
      Cronbach's alpha = 0.77, significant associations with adherence and health
      status indicators). Addressing adherence barriers in clinical practice with this
      population may help reduce their potential impact on behaviours.

PMID- 22985132
TI  - Expression and significance of the TLR4/MyD88 signaling pathway in ovarian
      epithelial cancers.
AB  - BACKGROUND: Toll-like receptors (TLR) are a family of pattern recognition
      receptors that constitutes a major part of the innate immune system. The
      TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown
      to have oncogenic effects. METHODS: To demonstrate the role of TLR4/MyD88
      signaling in ovarian epithelial cancers (OECs), we examined the expression of
      TLR4, MyD88 and nuclear factor- kappaB (NF-kappaB) in OECs. The expression of
      TLR4, MyD88, and NF-kappaB was detected by immunohistochemistry, and the
      relationships between these and clinicopathologic features in 123 cases of OECs
      were also analyzed. RESULTS: The expression of TLR4, MyD88, and NF-kappaB in OECs
      was observed in 46.3% (57/123), 36.6% (45/123) and 65% (80/123) of OEC cases,
      respectively. The TLR4, MyD88, and NF-kappaB expressions were associated with the
      histologic type of OECs, particularly with the clear cell type of OEC. There was
      no significant correlation between TLR4 or NF-kappaB expression and histologic
      grade, tumor size, mitotic count, FIGO (International Federation of Gynecology
      and Obstetrics) stage, disease recurrence. However, there was a significant
      correlation between MyD88 expression and FIGO stage, disease recurrence as well
      as histologic type. In univariate analysis, the expression of TLR4 and MyD88, and
      the coexpression of TLR4/MyD88 and TLR4/MyD88/NF-kappaB had a significant impact
      on the survival of patients with OECs. Only MyD88 expression had an independent
      prognostic significance in multivariate analysis. CONCLUSIONS: Our findings
      suggest that the TLR4/MyD88 signaling pathway is associated with the survival of
      patients with OECs, and that MyD88 is an independent prognostic predictor in
      patients with OECs. The TLR4/MyD88 signaling pathway may be a mechanism
      responsible for poor prognosis in patients with clear cell type of OEC.

PMID- 22985133
TI  - Corrole NH tautomers: spectral features and individual protonation.
AB  - Protonation of a free-base meso-pyrimidinyl-substituted AB(2)-corrole (H(3)AB(2))
      in ethanol solution by stepwise addition of sulfuric acid has been studied in the
      temperature range from 293 to 333 K. The formation rate of protonated species was
      found to depend profoundly on the temperature at which the titration was
      undertaken. Two steps in the titration curve were identified at temperatures
      around 293-298 K, whereas one-step formation of protonated species was found to
      occur at temperatures above 308 K. The protonation product was the same in both
      cases, i.e., H(4)AB(2)(+) corrole, protonated at the macrocycle core nitrogen
      atoms. The two steps in the protonation kinetics at lower temperatures were
      attributed to protonation of individual tautomers of the free-base H(3)AB(2)
      corrole. To the best of our knowledge, this is the first well-illustrated
      (spectrophotometric) observation of individual properties of corrole NH tautomers
      in fluid solution. Concomitant increase in the NH tautomerization rate with
      increasing temperature is proposed to account for the one-step protonation.
      Evidences for the role of individual corrole NH tautomers in the protonation
      process as well as their optical features are discussed based on spectroscopic
      results and simulation data.

PMID- 22985135
TI  - Indigenous Health: ACTION on Prevention - 50th annual Australian Society for
      Medical Research National Scientific Conference.
AB  - The 50th annual National Scientific Conference of the Australian Society for
      Medical Research was held in Cairns, Queensland, 13-16 November 2011. The theme,
      'Indigenous Health: ACTION on Prevention' highlighted the direct action being
      undertaken by health and medical researchers, as well as allied health
      professionals, to improve long-term health outcomes for Indigenous Australians.

PMID- 22985134
TI  - Dosing study of massage for chronic neck pain: protocol for the dose response
      evaluation and analysis of massage [DREAM] trial.
AB  - BACKGROUND: Despite the growing popularity of massage, its effectiveness for
      treating neck pain remains unclear, largely because of the poor quality of
      research. A major deficiency of previous studies has been their use of low
      "doses" of massage that massage therapists consider inadequate. Unfortunately,
      the number of minutes per massage session, sessions per week, or weeks of
      treatment necessary for massage to have beneficial or optimal effects are not
      known. This study is designed to address these gaps in our knowledge by
      determining, for persons with chronic neck pain: 1) the optimal combination of
      number of treatments per week and length of individual treatment session, and 2)
      the optimal number of weeks of treatment. METHODS/DESIGN: In this study, 228
      persons with chronic non-specific neck pain will be recruited from primary health
      care clinics in a large health care system in the Seattle area. Participants will
      be randomized to a wait list control group or 4 weeks of treatment with one of 5
      different dosing combinations (2 or 3 30-min treatments per week or 1, 2, or 3 60
      min treatments per week). At the end of this 4-week primary treatment period,
      participants initially receiving each of the 5 dosing combinations will be
      randomized to a secondary treatment period of either no additional treatment or 6
      weekly 60-min massages. The primary outcomes, neck-related dysfunction and pain,
      will be assessed by blinded telephone interviewers 5, 12, and 26 weeks post
      randomization. To better characterize the trajectory of treatment effects, these
      interview data will be supplemented with outcomes data collected by internet
      questionnaire at 10, 16, 20 and 39 weeks. Comparisons of outcomes for the 6
      groups during the primary treatment period will identify the optimal weekly dose,
      while comparisons of outcomes during the secondary treatment period will
      determine if 10 weeks of treatment is superior to 4 weeks. DISCUSSION: A broad
      dosing schedule was included in this trial. If adherence to any of these doses is
      poor, those doses will be discontinued. TRIAL REGISTRATION: This trial is
      registered in ClinicalTrials.gov, with the ID number of NCT01122836

PMID- 22985136
TI  - Hospital-acquired pressure ulcers: results from the national Medicare Patient
      Safety Monitoring System study.
AB  - OBJECTIVES: To determine the national and state incidence levels of newly
      hospital-acquired pressure ulcers (PUs) in Medicare beneficiaries and to describe
      the clinical and demographic characteristics and outcomes of these individuals.
      DESIGN: Retrospective secondary analysis of the national Medicare Patient Safety
      Monitoring System (MPSMS) database. SETTING: Medicare-eligible hospitals across
      the United States and select territories. PARTICIPANTS: Fifty-one thousand eight
      hundred forty-two randomly selected hospitalized fee-for-service Medicare
      beneficiaries discharged from the hospital between January 1, 2006, and December
      31, 2007. MEASUREMENTS: Data were abstracted from the MPSMS, which collects
      information on multiple hospital adverse events. RESULTS: Of the 51,842
      individuals in the MPSMS 2006/07 sample, 2,313 (4.5%) developed at least one new
      PU during their hospitalization. The mortality risk-adjusted odds ratios were
      2.81 (95% confidence interval (CI) = 2.44-3.23) for in-hospital mortality, 1.69
      (95% CI=1.61-1.77) for mortality within 30 days after discharge, and 1.33 (95% CI
      = 1.23-1.45) for readmission within 30 days. The hospital risk-adjusted main
      length of stay was 4.8 days (95% CI = 4.7-5.0 days) for individuals who did not
      develop PUs and 11.2 days (95% CI = 10.19-11.4) for those with hospital-acquired
      PUs (P < .001). The Northeast region and Missouri had the highest incidence rates
      (4.6% and 5.9%, respectively). CONCLUSION: Individuals who developed PUs were
      more likely to die during the hospital stay, have generally longer hospital
      lengths of stay, and be readmitted within 30 days after discharge.

PMID- 22985137
TI  - Validation of a cognitive assessment battery administered over the telephone.
AB  - OBJECTIVES: To evaluate the validity and reliability of a cognitive test battery
      and questionnaires administered by telephone. DESIGN: Observational study; 110
      participants randomly assigned to receive two administrations of the same
      cognitive test battery 6 months apart in one of four combinations (Time 1
      administration/Time 2 administration): telephone/telephone, telephone/face to
      face, face to face/telephone, face to face/face to face. SETTING: Academic
      medical center. PARTICIPANTS: One hundred ten women aged 65 to 90 without
      dementia. MEASUREMENTS: The battery included tests of attention; verbal learning
      and memory; verbal fluency; executive function; working memory; global cognitive
      functioning; and self-reported measures of perceived memory problems, depressive
      symptoms, sleep disturbance, and health-related quality of life. Test-retest
      reliability, concurrent validity, relative bias associated with telephone
      administration, and change scores were evaluated. RESULTS: There were no
      statistically significant differences in scores on any of the cognitive tests or
      questionnaires between participants randomly assigned to telephone or face-to
      face administration at the Time 1 assessment, indicating equivalence across
      administration modes. There was no significant bias for tests or questionnaires
      administered by telephone (P's > .01), nor was there a difference in mean change
      scores between administration modes except for Category Fluency (P = .01) and
      California Verbal Learning Test long-delay free recall (P = .004). Mean test
      retest coefficients for the battery were not significantly different between
      groups, although individual test-retest correlation coefficients were generally
      higher within modes than between modes. CONCLUSION: Telephone administration of
      cognitive tests and questionnaires to older women is reliable and valid. Use of
      telephone batteries can substantially reduce the cost and burden of cognitive
      assessments and increase enrollment, retention, and data completeness, thereby
      improving study validity.

PMID- 22985138
TI  - Contributions of environment, comorbidity, and stage of dementia to the onset of
      walking and eating disability in long-term care residents.
AB  - OBJECTIVES: To estimate the relative effects of environment, comorbidities, stage
      of dementia and other variables on disability onset. DESIGN: A 1-year prospective
      cohort study was conducted in which the walking and eating abilities of long-term
      care residents were observed fortnightly. Structural equation modeling was used
      to assess the contributions of individual and environmental factors to the onset
      of disability. SETTING: Fifteen nursing homes in western Canada. PARTICIPANTS:
      One hundred twenty residents with middle-stage Alzheimer disease or related
      dementia. MEASUREMENTS: Environmental quality was assessed using the Professional
      Environmental Assessment Protocol, comorbidity using the Charlson Comorbidity
      Index, and stage of dementia using the Global Deterioration Scale. RESULTS: More
      advanced baseline dementia had a direct effect on onset of walking and eating
      disability (standardized maximum likelihood estimate (SMLE) = 0.24, P = .006).
      Resident environment (SMLE = -0.25, P = .007) and comorbidities (SMLE = 0.32, P <
      .001) influenced disability onset approximately as strongly as stage of dementia.
      Smaller and publicly owned facilities provided superior environmental quality,
      which indirectly contributed to a delay in onset of walking and eating
      disability. CONCLUSION: Environmental quality and extent of comorbidity are at
      least as important as progression of dementia in initiating or delaying the onset
      of disability.

PMID- 22985139
TI  - Symptom burden predicts hospitalization independent of comorbidity in community
      dwelling older adults.
AB  - OBJECTIVES: To determine whether cumulative symptom burden predicts
      hospitalization or emergency department (ED) visits in a cohort of older adults.
      DESIGN: Prospective, observational study with a baseline in-home assessment of
      symptom burden. SETTING: Central Alabama. PARTICIPANTS: Nine hundred eighty
      community-dwelling adults aged 65 and older (mean 75.3 +/- 6.7) recruited from a
      random sample of Medicare beneficiaries stratified according to sex, race, and
      urban/rural residence. MEASUREMENTS: Symptom burden score (range 0-10). One point
      was given for each symptom reported: shortness of breath, tiredness or fatigue,
      problems with balance or dizziness, leg weakness, poor appetite, pain, stiffness,
      constipation, anxiety, and loss of interest in activities. Dependent variables
      were hospitalizations and ED visits, assessed every 6 months during the 8.5-year
      follow-up period. Using Cox proportional hazards models, time from the baseline
      in-home assessment to the first hospitalization and first hospitalization or ED
      visit was determined. RESULTS: During the 8.5-year follow-up period, 545 (55.6%)
      participants were hospitalized or had an ED visit. Participants with greater
      symptom burden had higher risk of hospitalization (hazard ratio (HR) = 1.09, 95%
      confidence interval (CI) = 1.05-1.14) and hospitalization or ED visit (HR = 1.10,
      95% CI = 1.06-1.14) than those with lower scores. Participants living in rural
      areas had significantly lower risk of hospitalization (HR = 0.83, 95% CI = 0.69
      0.99) and hospitalization or ED visit (HR = 0.80, 95% CI = 0.70-0.95) than
      individuals in urban areas, independent of symptom burden and comorbidity.
      CONCLUSION: Greater symptom burden was associated with higher risk of
      hospitalization and ED visits in community-dwelling older adults. Healthcare
      providers treating older adults should consider symptom burden to be an
      additional risk factor for subsequent hospital utilization.

PMID- 22985141
TI  - Association between timed up-and-go and memory, executive function, and
      processing speed.
AB  - OBJECTIVES: To determine which cognitive tests are independently associated with
      performance on the Timed Up-and-Go Test (TUG). DESIGN: Data were obtained from
      Wave 1 of The Irish Longitudinal Study on Ageing (TILDA), a population-based
      study assessing health, economic, and social aspects of aging. SETTING: Community
      dwelling adults completed a home based interview and a health center-based
      assessment. PARTICIPANTS: TILDA participants aged 50 and older with a Mini-Mental
      State Examination (MMSE) score of 10 or greater (N = 4,998). MEASUREMENTS:
      Participants completed a battery of cognitive assessments including the Montreal
      Cognitive Assessment (MoCA), Color Trails Test, word and letter fluency, choice
      reaction time, sustained attention, prospective memory, word recall, and picture
      memory. Linear regression was used to determine univariate and multivariate
      associations between TUG and each cognitive test. RESULTS: Slower TUG time was
      associated with poorer performance on all cognitive tests in univariate analysis
      (P < .05). In multivariate analysis, poorer performance on the MoCA, letter
      fluency, Color Trail 1, cognitive reaction time, mean sustained attention
      response time, and prospective memory were independently associated with slower
      TUG time (P < .05). CONCLUSION: Slower TUG time is independently associated with
      poorer performance on global cognition, executive function, and memory tests and
      slower processing speed. This highlights that TUG is more than just a simple
      mobility task and suggests that a comprehensive cognitive assessment is important
      for individuals with mobility difficulties.

PMID- 22985140
TI  - Enhanced fitness: a randomized controlled trial of the effects of home-based
      physical activity counseling on glycemic control in older adults with prediabetes
      mellitus.
AB  - OBJECTIVES: To determine whether a home-based multicomponent physical activity
      counseling (PAC) intervention is effective in reducing glycemic measures in older
      outpatients with prediabetes mellitus. DESIGN: Controlled clinical trial.
      SETTING: Primary care clinics of the Durham Veterans Affairs (VA) Medical Center
      between September 29, 2008, and March 25, 2010. PARTICIPANTS: Three hundred two
      overweight (body mass index 25-45 kg/m(2) ), older (60-89) outpatients with
      impaired glucose tolerance (fasting blood glucose 100-125 mg/dL, glycosylated
      hemoglobin (HbA1c) <7%) randomly assigned to a PAC intervention group (n = 180)
      or a usual care control group (n = 122). INTERVENTION: A 12-month, home-based
      multicomponent PAC program including one in-person baseline counseling session,
      regular telephone counseling, physician endorsement in clinic with monthly
      automated encouragement, and customized mailed materials. All study participants,
      including controls, received a consultation in a VA weight management program.
      MEASUREMENTS: The primary outcome was a homeostasis model assessment of insulin
      resistance (HOMA-IR), calculated from fasting insulin and glucose levels at
      baseline and 3 and 12 months. HbA1c was the secondary indicator of glycemic
      control. Other secondary outcomes were anthropometric measures and self-reported
      physical activity, health-related quality of life, and physical function.
      RESULTS: There were no significant differences between the PAC and control groups
      over time for any of the glycemic indicators. Both groups had small declines over
      time of approximately 6% in fasting blood glucose (P < .001), and other glycemic
      indicators remained stable. The declines in glucose were not sufficient to affect
      the change in HOMA-IR scores due to fluctuations in insulin over time. Endurance
      physical activity increased significantly in the PAC group (P < .001) and not in
      the usual care group. CONCLUSION: Home-based telephone counseling increased
      physical activity levels but was insufficient to improve glycemic indicators in
      older outpatients with prediabetes mellitus.

PMID- 22985143
TI  - Is frailty a prodromal stage of vascular dementia? Results from the Three-City
      Study.
AB  - OBJECTIVES: To investigate the relationship between frailty and incident vascular
      dementia (VaD). DESIGN: Seven-year longitudinal study. SETTING: Three-City Study,
      a French prospective study designed to evaluate the risk of dementia and
      cognitive decline attributable to vascular risk factors. PARTICIPANTS: Five
      thousand four hundred eighty community-dwelling persons aged 65 to 95.
      MEASUREMENTS: An expert committee established a clinical diagnosis of VaD.
      Frailty was defined as having at least three of the following criteria: weight
      loss, weakness, exhaustion, slowness, and low physical activity. Participants
      with prior stroke or prevalent dementia at baseline were excluded from analyses.
      Multivariate models were used to evaluate the relationship between frailty and
      incident VaD. RESULTS: At baseline, 6.5% of participants were classified as
      frail. After 7 years of follow-up, 54 persons were diagnosed with VaD, seven of
      whom where frail. In the proportional hazards models, frailty was marginally
      associated with greater risk of all types of dementia and was not associated with
      incident Alzheimer's disease, but frailty status was independently associated
      with incident VaD. CONCLUSION: Frailty is a major risk factor for incident VaD,
      so its identification could contribute to better estimates of the risk of VaD in
      elderly adults.

PMID- 22985142
TI  - Resting metabolic rate in old-old women with and without frailty: variability and
      estimation of energy requirements.
AB  - OBJECTIVES: To measure resting metabolic rate (RMR) in old-old adults living in
      the community and examine the association between measured RMR and frailty status
      and compare it with expected RMR generated by a predictive equation. DESIGN:
      Physiological substudy conducted as a home visit within an observational cohort
      study. SETTING: Baltimore City and County, Maryland. PARTICIPANTS: Seventy-seven
      women aged 83 to 93 enrolled in the Women's Health and Aging Study II.
      MEASUREMENTS: Resting metabolic rate with indirect calorimetry, frailty status,
      fat-free mass, ambient and body temperature, expected RMR according to the
      Mifflin-St. Jeor equation. RESULTS: Average RMR was 1,119 +/- 205 kcal/d (range
      595-1,560 kcal/d). Agreement between observed and expected RMR was biased and
      poor (between-subject coefficient of variation 38.0%, 95% confidence interval =
      35.1-40.8). Variability of RMR was greater in frail individuals
      (heteroscedasticity F-test P = .02). Low and high RMR were associated with being
      frail (odds ratio 5.4, P = .04) and slower self-selected walking speed (P < .001)
      after adjustment for covariates. CONCLUSION: Equations to predict RMR that are
      not validated in old-old adults appear to correlate poorly with measured RMR. RMR
      is highly variable in old-old women, with deviations from the mean predicting
      clinical frailty. These exploratory findings suggest a pathway to clinical
      frailty through high or low RMR.

PMID- 22985144
TI  - Clinical care of persons with dementia in the emergency department: a review of
      the literature and agenda for research.
AB  - The segment of older adults who present to the emergency department (ED) with
      cognitive impairment ranges from 21% to 40%. Difficulties inherent in the chaotic
      ED setting combined with dementia may result in a number of unwanted clinical
      outcomes, but strategies to minimize these outcomes are lacking. A review of the
      literature was conducted to examine the practices undertaken in the care of
      persons with dementia (PWD) specific to the ED setting. PubMed and Cumulative
      Index to Nursing and Allied Health Literature were searched for published
      articles specific to the care of PWD provided in the ED. All English-language
      articles were reviewed; editorials and reflective journals were excluded. Seven
      articles ultimately met inclusion criteria; all provided Level 7 evidence:
      narrative review or opinions from authorities. The articles recommended clinical
      practices that can be categorized into five themes: assessment of cognitive
      impairment, dementia communication strategies, avoidance of adverse events,
      alterations to the physical environment, and education of ED staff. Many
      recommendations are extrapolated from residential care settings. Review results
      indicate that there is minimal guidance for the care of PWD specific to the ED
      setting. There are no empirical studies of the care (assessment, interventions)
      of PWD in the ED. The existing (Level 7) recommendations lack a research base to
      support their effectiveness or adoption as evidence-based practice. There is a
      significant opportunity for research to identify and test ways to meet the needs
      of PWD in the ED to ensure a safe visit, accurate diagnosis, and prudent transfer
      to the most appropriate level of care.

PMID- 22985145
TI  - Systematic review of bone health in older women treated with aromatase inhibitors
      for early-stage breast cancer.
AB  - OBJECTIVES: To review data from randomized controlled trials (RCTs) that evaluate
      adverse bone outcomes in older women using aromatase inhibitors (AIs) for early
      stage hormone receptor-positive breast cancer. DESIGN: Systematic review.
      SETTING: International RCTs referenced in Medline and EMBASE databases through
      August 1, 2011. PARTICIPANTS: Postmenopausal women with early-stage hormone
      receptor-positive breast cancer receiving adjuvant endocrine therapy.
      MEASUREMENTS: Fracture rates and changes in bone turnover markers and bone
      mineral density. RESULTS: Eleven RCTs were identified. The majority of trials
      included women with a mean age in the 60s; and women aged 75 and older and 80 and
      older were excluded from two studies. Fracture rates ranged from 0.9% to 11%,
      with AIs having a 1.5 times higher risk than tamoxifen or placebo. Fracture data
      were not systematically collected in many of these trials. In a small
      subpopulation of women, AIs were associated with higher markers of bone turnover
      and lower bone density. The relationship between age and fracture was not
      described. CONCLUSION: AIs are associated with low bone density and high fracture
      risk in women with a mean age in their early 60s. There is a paucity of data
      describing the effect of baseline fracture risk factors, particularly age, and
      the longer-term effects on bone health in older women. Future research is needed
      regarding baseline fracture risk, interventions, and long-term effects on bone in
      this vulnerable population to inform management decisions to optimize AI duration
      and ensure quality of life after breast cancer.

PMID- 22985146
TI  - Aging and the energetic cost of life.

PMID- 22985147
TI  - "Occupy nature": passing activism across generations.

PMID- 22985148
TI  - Transcatheter aortic valve implantation: how old is too old?

PMID- 22985149
TI  - Transcatheter aortic valve implantation in a 99-year-old woman: are we going too
      far?

PMID- 22985151
TI  - Primary central nervous system posttransplantation lymphoproliferative disorder
      in an elderly liver transplant recipient.

PMID- 22985150
TI  - Association between uterine prolapse and cervical squamous cell carcinoma in an
      elderly adult.

PMID- 22985152
TI  - Surviving a crisis of immobilization hypercalcemia.

PMID- 22985153
TI  - A case of Diogenes syndrome: clinical and ethical challenges.

PMID- 22985154
TI  - Nintendo Wii as a training tool in falls prevention rehabilitation: case studies.

PMID- 22985155
TI  - Uric acid and mortality in elderly Chinese: a 10-year population-based cohort
      study.

PMID- 22985156
TI  - Relationship between thinness and swallowing function in Japanese older adults:
      implications for sarcopenic dysphagia.

PMID- 22985157
TI  - Prevalence of the long-allele genotype of the serotonin transporter-linked gene
      in female centenarians.

PMID- 22985158
TI  - Relationship between physical condition, functional fitness, and falls risk in
      elderly adults.

PMID- 22985159
TI  - Teaching geriatrics to gynecology residents: are American Congress of
      Obstetricians and Gynecologists learning objectives being met?

PMID- 22985160
TI  - Hospital transfers of nursing home residents with dementia.

PMID- 22985161
TI  - A pilot study to develop a brief question-based screening tool to identify higher
      risk older drivers.

PMID- 22985162
TI  - Magnesium homeostasis and metabolic complications in elderly adults with chronic
      kidney disease.

PMID- 22985163
TI  - Functional recovery in hospitalized elderly adults.

PMID- 22985165
TI  - Future direction of geriatrics: "gerogeriatrics": a comment.

PMID- 22985167
TI  - Lateral distribution of charged species along a polyelectrolyte probed with a
      fluorescence blob model.
AB  - The distribution of metal counterions binding onto the oppositely charged surface
      of a model polyelectrolyte, namely, DNA, was characterized by conducting
      fluorescence quenching experiments. In these experiments, DNA was used as a
      molecular ruler to measure the average distance (d(blob)) over which electron
      transfer takes place between DNA-intercalated ethidium bromide (DNA-EB) and the
      electrostatically bound divalent metal cations Ni(2+) and Cu(2+). Analysis of the
      fluorescence decays of DNA-EB quenched by Cu(2+) and Ni(2+) with the fluorescence
      blob model showed that d(blob) was equal to the Debye length (kappa(-1)). This
      surprisingly simple result considering the overall complexity of the system under
      study led to the straightforward proposal that counterions bind to a
      polyelectrolyte by distributing themselves randomly into an array of self-defined
      subdomains of dimension kappa(-1). In turn, this insight can be utilized to
      rationalize the complex behavior of polyelectrolytes in aqueous solution.

PMID- 22985170
TI  - Highly concentrated aqueous suspensions of graphene through ultrasonic
      exfoliation with continuous surfactant addition.
AB  - Highly concentrated suspensions of graphene stabilized with surfactant were
      prepared using ultrasonic exfoliation. Concentrations of up to 1.5% w/w (15
      mg/mL) were achieved through the continuous addition of the surfactant during the
      exfoliation process. Previous methods typically add the surfactant only once,
      prior to the commencement of sonication. The vast increase in the available solid
      liquid interfacial area through delamination results in the rapid depletion of
      the surfactant from solution through adsorption. This leads to a change in the
      liquid-vapor surface tension outside of the optimum range for the efficient
      production of graphene sheets. By continuously replacing the surfactant to lower
      the surface tension during sonication and the production of the graphene surface
      area, the concentration of particles was significantly increased. Cationic,
      anionic, and nonionic surfactants were studied and all showed significant
      increases in the concentration of graphene produced using this continuous
      addition method.

PMID- 22985168
TI  - Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target
      unmutated BCR-ABL and BCR-ABL-T315I.
AB  - BACKGROUND: Chronic myelogenous leukemia (CML) and Philadelphia chromosome
      positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22),
      which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The
      constitutively activated BCR/ABL-kinase "escapes" the auto-inhibition mechanisms
      of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs)
      Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are
      effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL
      restores allosteric inhibition. Given the fact that all AKIs fail to inhibit
      BCR/ABL harboring the 'gatekeeper' mutation T315I, we investigated the effects of
      AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia. METHODS:
      The efficacy of this approach on the leukemogenic potential of BCR/ABL was
      studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1
      fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived
      long-term cultures (PDLTC) from Ph + ALL-patients. RESULTS: Here, we show that
      GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the
      combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all
      models used in a synergistic manner. CONCLUSIONS: Our observations establish a
      new approach for the molecular targeting of BCR/ABL and its resistant mutants
      using a combination of AKIs and allosteric inhibitors.

PMID- 22985169
TI  - A pictorial essay of brain perfusion-CT: not every abnormality is a stroke!
AB  - Perfusion-CT (PCT) of the brain is a rapidly evolving imaging technique used to
      assess blood supply to the brain parenchyma. PCT is readily available at most
      imaging centers, resulting in steadily increasing use of this imaging technique.
      Though PCT was initially introduced and still most widely used to evaluate
      patients with acute ischemic stroke, a wide variety of other pathologic processes
      demonstrate abnormal perfusion maps. Therefore, it is important for the
      radiologist to recognize altered perfusion patterns observed in diseases other
      than typical ischemic stroke. The goal of this article is to show the perfusion
      maps and review the perfusion patterns observed in some subtypes of atypical
      stroke and in neurological entities other than stroke, so that they are
      recognized and not confused with the PCT patterns observed in patients with
      typical ischemic stroke.

PMID- 22985171
TI  - Modeling population immunity to support efforts to end the transmission of live
      polioviruses.
AB  - Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of
      circulating vaccine-derived polioviruses, and achievement and maintenance of a
      world free of paralytic polio cases requires active risk management by focusing
      on population immunity and coordinated cessation of oral poliovirus vaccine
      (OPV). We suggest the need for a complementary and different conceptual approach
      to achieve eradication compared to the current case-based approach using
      surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus
      infections. Specifically, we describe a modeling approach to characterize overall
      population immunity to poliovirus transmission. The approach deals with the
      realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination
      with inactivated poliovirus vaccine provides protection from paralytic polio
      (i.e., disease), but does not eliminate the potential for reinfection or
      asymptomatic participation in poliovirus transmission, which may increase with
      time because of waning immunity. The AFP surveillance system provides evidence of
      symptomatic poliovirus infections detected, which indicate immunity gaps after
      outbreaks occur, and this system represents an appropriate focus for controlling
      disease outbreaks. We describe a conceptual dynamic model to characterize
      population immunity to poliovirus transmission that helps identify risks created
      by immunity gaps before outbreaks occur, which provides an opportunity for
      national and global policymakers to manage the risk of poliovirus and prevent
      outbreaks before they occur. We suggest that dynamically modeling risk represents
      an essential tool as the number of cases approaches zero.

PMID- 22985173
TI  - Cell-based delivery of glucagon-like peptide-1 using encapsulated mesenchymal
      stem cells.
AB  - Glucagon-like peptide-1 (GLP-1) CellBeads are cell-based implants for the
      sustained local delivery of bioactive factors. They consist of GLP-1 secreting
      mesenchymal stem cells encapsulated in a spherically shaped immuno-isolating
      alginate matrix. A highly standardized and reproducible encapsulation method is
      described for the manufacturing of homogeneous CellBeads. Viability and sustained
      secretion was shown for the recombinant GLP-1 and the cell endogenous bioactive
      factors like vascular endothelial growth factor, neurotrophin 3 (NT-3) and glial
      cell line-derived neurotrophic factor. Manufacturing and quality control is
      performed in compliance with good manufacturing practice and fulfils all
      regulatory requirements for human clinical use. GLP-1 CellBeads combine the neuro
      and cardioprotective properties of both GLP-1 and mesenchymal stem cells. First
      promising results were obtained from preclinical studies and an ongoing safety
      trial in humans but further studies have to prove the overall potential of
      CellBead technology in cell-based regenerative medicine.

PMID- 22985172
TI  - A role for an endosperm-localized subtilase in the control of seed size in
      legumes.
AB  - Here, we report a subtilase gene (SBT1.1) specifically expressed in the endosperm
      of Medicago truncatula and Pisum sativum seeds during development, which is
      located at a chromosomal position coinciding with a seed weight quantitative
      trait locus (QTL). Association studies between SBT1.1 polymorphisms and seed
      weights in ecotype collections provided further evidence for linkage
      disequilibrium between the SBT1.1 locus and a seed weight locus. To investigate
      the possible contribution of SBT1.1 to the control of seed weight, a search for
      TILLING (Targeting Induced Local Lesions in Genomes) mutants was performed. An
      inspection of seed phenotype revealed a decreased weight and area of the sbt1.1
      mutant seeds, thus inferring a role of SBT1.1 in the control of seed size in the
      forage and grain legume species. Microscopic analyses of the embryo, representing
      the major part of the seed, revealed a reduced number of cells in the MtP330S
      mutant, but no significant variation in cell size. SBT1.1 is therefore most
      likely to be involved in the control of cotyledon cell number, rather than cell
      expansion, during seed development. This raises the hypothesis of a role of
      SBT1.1 in the regulation of seed size by providing molecules that can act as
      signals to control cell division within the embryo.

PMID- 22985174
TI  - Early improvement of the regional and global ventricle function estimated by two
      dimensional speckle tracking echocardiography after percutaneous aortic valve
      implantation speckle tracking after CoreValve implantation.
AB  - BACKGROUND: To assess changes in myocardial deformation and ejection fraction
      (EF) by two-dimensional speckle tracking echocardiography (2DSTE) after
      transcatheter aortic valve implantation (TAVI). METHODS: A total of 24 patients
      (50% males, age 78 +/- 4 years) were selected for TAVI because of severe aortic
      stenosis. A comprehensive echocardiographic study was performed before TAVI, at
      discharge, and after 1-month follow-up. EF was assessed by 2D conventional
      echocardiography with Simpson method and by 2DSTE. Radial and circumferential
      strains were evaluated in six segments in the short-axis view at the level of the
      papillary muscles, and longitudinal strain in six segments in the four-chamber
      apical view, by means of 2DSTE. All studies were performed with an iE-33
      echocardiography device (Philips). RESULTS: At discharge, the mean EF estimated
      by 2DSTE improved significantly when compared with the basal one (56 +/- 7% vs.
      51 +/- 8%, P < 0.01), while EF by Simpson method did not change (67 +/- 9% vs. 64
      +/- 16%, P = 0.2). At that time, global radial (21.4 +/- 9% vs. 11.5 +/- 7.6%, P
      = 0.000), circumferential (-20.7 +/- 8% vs. -15.2 +/- 7%, P = 0.02), and
      longitudinal strains (-14.8 +/- 6.2% vs. -12 +/- 6%, P = 0.02) improved
      significantly when compared with the basal one. At 1-month follow-up, global
      radial (20.1 +/- 5.6% vs. 21.4 +/- 9%, P = 0.88) and circumferential (-20 +/- 8%
      vs. -20.7 +/- 8%, P = 0.35) strains did not vary and a new significant
      improvement was observed in longitudinal global strain (-19.2 +/- 6.5% vs. -14.8
      +/- 6.2%, P = 0.002). CONCLUSIONS: A new echocardiographic technique, such as
      2DSTE, shows a significant early improvement in global and segmental left
      ventricular systolic function after TAVI, which could not be detected by
      conventional methods.

PMID- 22985176
TI  - Ceramides as possible nutraceutical compounds: characterization of the ceramides
      of the Moro blood orange ( Citrus sinensis ).
AB  - Ceramides are presented as nutraceutical compounds for protection of colon
      carcinoma and as important cosmetic preparation components, increasing absorption
      through the skin. Therefore, the ceramide (Cer) content of Moro blood oranges was
      determined by mass spectrometry. A total of 114 Cer species were identified: ~160
      mg in the peels and ~140 mg in the pulp per kilogram of oranges, expressed as
      "milligram equivalents of d18:1,17:0 Cer". The predominant ceramides contained 4
      hydroxy-8-sphingenine (t18:1(Delta8)) and 4-hydroxysphinganine (t18:0) as long
      chain bases (LCBs) and fatty acids (FAs) with different structures. In the pulp,
      t18:1(Delta8)- and t18:0-containing Cer species comprised 50.5 and 33.5% of the
      total, respectively, 11.5 and 3.5% non-hydroxylated FAs, respectively, 32.0 and
      21.0% alpha-hydroxylated FAs, respectively, and 7.0 and 9.0% alpha,beta
      hydroxylated FAs, respectively. In the peels, t18:1(Delta8)- and t18:0-containing
      species comprised 49.5 and 34.5% of the total, respectively, 16.0 and 1.5% non
      hydroxylated FAs, respectively, 31.5 and 29.0% alpha-hydroxylated FAs,
      respectively, and 2.0 and 4.0% alpha,beta-hydroxylated FAs, respectively. 

PMID- 22985175
TI  - New antimicrobial, mosquito larvicidal and other metabolites from two Artabotrys
      species.
AB  - Azabicycloheptenoylditerpene 1-((2E,6E,10E)-3,7,11,15-tetramethylhexadeca
      2,6,10,14-tetraenyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (artamodamide, 1),
      diphenylpentanoid (E)-1,5-bis(4-hydroxyphenyl)-pent-1-en-3-one (artamenone, 2)
      and N-methoxy-5-oxoaporphinoid (artamonteirine, 3) were isolated as new
      metabolites from Artabotrys modestus Diels ssp macranthus Verdc. and Artabotrys
      monteiroae Oliv. (Annonaceae), together with several known compounds. Structures
      of the isolated compounds were established based on analysis of their
      spectroscopic data. Some of the compounds exhibited antimicrobial activity
      (minimum inhibitory concentration values between 2.5 and 20 ug mL-1) and varying
      levels of mosquito larvicidal potency. These results further indicate the
      versatility of the family Annonaceae in accumulating bioactive natural products
      with diverse chemical structures and wide spectra of biological activities, and
      hence suggesting the need to conserve Annonaceae species that are potentially
      vulnerable to extinction.

PMID- 22985177
TI  - Association between hospital volume and outcomes of elderly and non-elderly
      patients with acute biliary diseases: a national administrative database
      analysis.
AB  - AIM: This study aimed to investigate the relationship between hospital volume and
      clinical outcomes of elderly and non-elderly patients with acute biliary diseases
      using data from a national administrative database. METHODS: Overall, 26720
      elderly and 33774 non-elderly patients with acute biliary diseases were referred
      to 820 hospitals in Japan. Hospital volume was categorized into three groups
      based on the case numbers during the study period: low-volume, medium-volume and
      high-volume. We compared the risk-adjusted length of stay (LOS) and in-hospital
      mortality in relation to hospital volume. These analyses were stratified
      according to the presence of invasive treatments for acute biliary diseases.
      RESULTS: Multiple linear regression analyses showed that increased hospital
      volume was significantly associated with shorter LOS in both elderly and non
      elderly patients with and without invasive treatments. Increased hospital volume
      was significantly associated with decreased relative risk of in-hospital
      mortality in elderly patients. The odds ratio for high-volume hospitals was 0.672
      in elderly patients without invasive treatments (95% confidence interval [CI]
      0.533-0.847, P=0.001) and 0.715 in those with invasive treatments (95% C, 0.566
      0.904, P=0.005). However, no significant differences for in-hospital mortality
      were seen in non-elderly patients with and without invasive treatments.
      CONCLUSION:   This study has highlighted that higher volume hospitals
      significantly reduced LOS and in-hospital mortality for elderly patients with
      acute biliary diseases, but not non-elderly patients. The current results are of
      value for elderly healthcare policy decision-making, and highlight the need for
      further studies into the quality of care for elderly patients.

PMID- 22985178
TI  - Sobering up: a quantitative review of temporal declines in expectations.
AB  - Although people's outlook on the future tends to be characterized by hope and
      optimism, over time this outlook often becomes more dire. We review multiple
      theoretical accounts of this tendency to "sober up" as feedback about outcomes
      draws near, and we explicate factors critical to promoting these temporal
      declines in expectations. We then meta-analytically test the impact of these
      factors on temporal shifts in people's expectations about self-relevant outcomes.
      The findings reveal a robust and ubiquitous tendency to lower one's expectations
      as the moment of feedback draws near and implicate multiple contributing
      processes (declining control, changing accountability pressures, construal level
      changes, and affect management concerns) as important for this shift.
      Furthermore, the results reveal important differences in the methodological
      approaches used to examine temporal shifts in predictions and suggest that timing
      of predictions relative to outcomes and feedback plays a critical role in the
      nature of the phenomenon. Overall, the analysis reveals an important exception to
      positive illusions about the future and suggests that a time-sensitive turn
      toward pessimism has adaptive functions.

PMID- 22985179
TI  - Designed architecture of multiscale porous TiO2 nanofibers for dye-sensitized
      solar cells photoanode.
AB  - Multiscale porous (MSP) TiO(2) nanofibers (NFs) were fabricated using a simple
      electrospinning and etching process with TiO(2)/SiO(2) composite NFs for high
      efficiency dye-sensitized solar cells (DSSCs). TiO(2) NFs with different pore
      sizes (small, large, and multiscale) were prepared using SiO(2) nanoparticles of
      various sizes. The surface area of the MSP TiO(2) NFs was nine times higher than
      that of pristine TiO(2) NFs, providing sufficient dye adsorption for light
      harvesting as well as efficient paths for electrolyte contact. Moreover, the one
      dimensional structure provides efficient light scattering and fast electron
      transport. As a result, DSSCs exhibited an enhanced current density (J(sc)) of
      16.3 mA cm(-2) and a high photoconversion efficiency (eta) of 8.5%, greater than
      those of conventional photoelectrodes made of TiO(2) nanoparticles (J(sc) of 12.0
      mA cm(-2) and eta of 6.0 %).

PMID- 22985180
TI  - From microbes to numbers: extracting meaningful quantities from images.
AB  - Light microscopy offers a unique window into the life and works of microbes and
      their interactions with hosts. Mere visualization of images, however, does not
      provide the quantitative information needed to reliably and accurately
      characterize phenotypes or test computational models of cellular processes, and
      is unfeasible in high-throughput screens. Algorithms that automatically extract
      biologically meaningful quantitative data from images are therefore an
      increasingly essential complement to the microscopes themselves. This paper
      reviews some of the computational methods developed to detect, segment and track
      cells, molecules or viruses, with an emphasis on their underlying assumptions,
      limitations, and the importance of validation.

PMID- 22985181
TI  - Disorder limited exciton transport in colloidal single-wall carbon nanotubes.
AB  - We present measurements of S(1) exciton transport in (6,5) carbon nanotubes at
      room temperature in a colloidal environment. Exciton diffusion lengths associated
      with end quenching paired with photoluminescence lifetimes provide a direct basis
      for determining a median diffusion constant of approximately 7.5 cm(2)s(-1). Our
      experimental results are compared to model diffusion constants calculated using a
      realistic exciton dispersion accounting for a logarithmic correction due to the
      exchange self-energy and a nonequilibrium distribution between bright and dark
      excitons. The intrinsic diffusion constant associated with acoustic phonon
      scattering is too large to explain the observed diffusion length, and as such, we
      attribute the observed transport to disorder-limited diffusional transport
      associated with the dynamics of the colloidal interface. In this model an
      effective surface potential limits the exciton mean free path to the same size as
      that of the exciton wave function, defined by the strength of the electron-hole
      Coulomb interaction.

PMID- 22985182
TI  - Genome-wide association study for T lymphocyte subpopulations in swine.
AB  - BACKGROUND: Lymphocytes act as a major component of the adaptive immune system,
      taking very crucial responsibility for immunity. Differences in proportions of T
      cell subpopulations in peripheral blood among individuals under same conditions
      provide evidence of genetic control on these traits, but little is known about
      the genetic mechanism of them, especially in swine. Identification of the genetic
      control on these variants may help the genetic improvement of immune capacity
      through selection. RESULTS: To identify genomic regions responsible for these
      immune traits in swine, a genome-wide association study was conducted. A total of
      675 pigs of three breeds were involved in the study. At 21 days of age, all
      individuals were vaccinated with modified live classical swine fever vaccine.
      Blood samples were collected when the piglets were 20 and 35 days of age,
      respectively. Seven traits, including the proportions of CD4+, CD8+, CD4+CD8+,
      CD4+CD8-, CD4-CD8+, CD4-CD8- and the ratio of CD4+ to CD8+ T cells were measured
      at the two ages. All the samples were genotyped for 62,163 single nucleotide
      polymorphisms (SNP) using the Illumina porcineSNP60k BeadChip. 40833 SNPs were
      selected after quality control for association tests between SNPs and each immune
      trait considered based on a single-locus regression model. To tackle the issue of
      multiple testing in GWAS, 10,000 permutations were performed to determine the
      chromosome-wise and genome-wise significance levels of association tests. In
      total, 61 SNPs with chromosome-wise significance level and 3 SNPs with genome
      wise significance level were identified. 27 significant SNPs were located within
      the immune-related QTL regions reported in previous studies. Furthermore, several
      significant SNPs fell into the regions harboring known immunity-related genes, 14
      of them fell into the regions which harbor some known T cell-related genes.
      CONCLUSIONS: Our study demonstrated that genome-wide association studies would be
      a feasible way for revealing the potential genetics variants affecting T-cell
      subpopulations. Results herein lay a preliminary foundation for further
      identifying the causal mutations underlying swine immune capacity in follow-up
      studies.

PMID- 22985184
TI  - Cuff filling volumes for pediatric classic laryngeal mask airways: comparison of
      clinical end points versus adjusted cuff pressure.
AB  - BACKGROUND: Clinical end points are often used to guide inflation and adequacy of
      cuff seal after laryngeal mask airway placement. However, clinical end points for
      cuff inflation have been shown to have significantly higher intracuff pressure.
      The adjusted cuff pressure between 55 and 60 cm H(2)O causes significantly better
      seal of laryngeal mask airway. We prospectively assessed the cuff pressures
      generated by cuff inflation guided by clinical end points, and the actual volume
      of air required to achieve cuff pressures between 55 and 60 cm H(2)O for sizes 1
      2.5 reusable classic laryngeal mask airway. METHODS: Two hundred and three ASA I
      and II children undergoing elective cataract surgery requiring general anesthesia
      receiving laryngeal mask airway sizes 1-2.5 were recruited to this study. The
      laryngeal mask airway was placed using standard technique. After insertion of
      laryngeal mask airway, the cuff was slowly inflated until a slight outward shift
      of device was noted. Cuff pressures were measured using calibrated hand held
      Portex Cuff Inflator Pressure Gauge (Portex Limited, Hythe, Kent, UK). If the
      cuff pressure was >60 cm H(2)O, the cuff was deflated to achieve a cuff pressure
      of 55-60 cm H(2)O. The volume of air required to achieve this pressure was
      recorded. RESULTS: The volume of air required to achieve the pressure between 55
      and 60 cm H(2)O in laryngeal mask airway size 1, 1.5, 2.0, and 2.5 were 2.750 +/-
      0.2565, 4.951 +/- 0.5378, 6.927 +/- 0.6328, and 10.208 +/- 1.4535 ml,
      respectively. The difference between the initial and the final cuff volumes and
      pressures in all laryngeal mask airway sizes were statistically significant(P =
      0.000). CONCLUSION: Lower cuff volumes are required to achieve a pressure of 60
      cm H(2)O than those required if clinical end points are used as a sole guide for
      determining cuff inflation for patients receiving pediatric laryngeal mask
      airways.

PMID- 22985185
TI  - A strategy for large-scale phosphoproteomics and SRM-based validation of human
      breast cancer tissue samples.
AB  - Protein phosphorylation is a key mechanism of cellular signaling pathways and
      aberrant phosphorylation has been implicated in a number of human diseases. Thus,
      approaches in phosphoproteomics can contribute to the identification of key
      biomarkers to assess disease pathogenesis and drug targets. Moreover, careful
      validation of large-scale phosphoproteome analysis, which is lacking in the
      current protein-based biomarker discovery, significantly increases the value of
      identified biomarkers. Here, we performed large-scale differential
      phosphoproteome analysis using IMAC coupled with the isobaric tag for relative
      quantification (iTRAQ) technique and subsequent validation by selected/multiple
      reaction monitoring (SRM/MRM) of human breast cancer tissues in high- and low
      risk recurrence groups. We identified 8309 phosphorylation sites on 3401
      proteins, of which 3766 phosphopeptides (1927 phosphoproteins) were able to be
      quantified and 133 phosphopeptides (117 phosphoproteins) were differentially
      expressed between the two groups. Among them, 19 phosphopeptides were selected
      for further verification and 15 were successfully quantified by SRM using stable
      isotope peptides as a reference. The ratio of phosphopeptides between high- and
      low-risk groups quantified by SRM was well correlated with iTRAQ-based
      quantification with a few exceptions. These results suggest that large-scale
      phosphoproteome quantification coupled with SRM-based validation is a powerful
      tool for biomarker discovery using clinical samples.

PMID- 22985186
TI  - Reactome - a curated knowledgebase of biological pathways: megakaryocytes and
      platelets.

PMID- 22985187
TI  - Conjunctival lymphoma arising from reactive lymphoid hyperplasia.
AB  - Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically
      arises in the marginal zone of mucosa-associated lymphoid tissue. The
      pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of
      EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35
      year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus
      uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter
      (OD), revealed a collection of small lymphoid cells in the stroma.
      Immunohistochemically, immunoglobulin (Ig) light chain restriction was not
      detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in
      the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells
      OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis
      detected IgH gene rearrangement in the joining region (JH) region OU. After 11
      months, a re-biopsy specimen demonstrated EMZL based on compatible pathological
      and genetic findings OD, arising from RLH. This case suggests that even if the
      diagnosis of the conjunctival lymphoproliferative lesions is histologically
      benign, confirmation of the B-cell clonality by checking IgH gene rearrangement
      should be useful to predict the incidence of malignancy.

PMID- 22985189
TI  - Cosuspensions of microcrystals and engineered microparticles for uniform and
      efficient delivery of respiratory therapeutics from pressurized metered dose
      inhalers.
AB  - Engineered porous phospholipid microparticles with aerodynamic diameters in the
      respirable range of 1-2 MUm were cosuspended in 1,1,1,2-tetrafluoroethane, a
      propellant, with microcrystals of glycopyrrolate, formoterol fumarate dihydrate,
      or Mometasone furoate-three drugs with different solubilities in the propellant,
      and different physical, chemical, and pharmacological attributes. The drug
      microcrystals were added individually, in pairs, or all three together to prepare
      different cosuspensions, contained in a pressurized metered dose inhaler (pMDI).
      The drug microcrystals irreversibly associated with the porous particles, and the
      resultant cosuspensions possessed greatly improved suspension stability compared
      with suspensions of drug microcrystals alone. In general, all cosuspensions
      showed efficient dose delivery of the drugs, with fine particle fractions of more
      than 60% for a wide range of doses, including those as low as 300 ng per inhaler
      actuation. In the cosuspension pMDIs, comparable fine particle fractions were
      delivered for all tested drugs, whether or not they were emitted from an inhaler
      containing one, two, or three drugs. We demonstrate that the cosuspension
      approach solves at least three long-standing problems in the clinical development
      of pMDI-based products: (1) dose and drug dependent delivery efficiency, (2)
      inability to formulate dose strengths below 1 MUg to fully explore drug efficacy
      and safety, and (3) combination suspensions delivering a different fine particle
      fraction than individual drug suspensions.

PMID- 22985188
TI  - Circulating hematopoietic stem cell count is a valuable predictor of prematurity
      complications in preterm newborns.
AB  - BACKGROUND: The frequency of preterm labour has risen over the last few years.
      Hence, there is growing interest in the identification of markers that may
      facilitate prediction and prevention of premature birth complications. Here, we
      studied the association of the number of circulating stem cell populations with
      the incidence of complications typical of prematurity. METHODS: The study groups
      consisted of 90 preterm (23-36 weeks of gestational age) and 52 full-term (37-41
      weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+),
      enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent
      (Oct-4, Nanog), early neural (beta-III-tubulin), and oligodendrocyte lineage
      (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and
      circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in
      association with characteristics of prematurity and preterm morbidity were
      analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after
      delivery. Phenotype analysis was performed using flow cytometry methods.
      Clonogenic assays suitable for detection of human hematopoietic progenitor cells
      were also applied. The quantitative parameters were compared between groups by
      the Mann-Whitney test and between time points by the Friedman test. Fisher's
      exact test was used for qualitative variables. RESULTS: We found that the number
      of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm
      infants. More notably, a high number of CB HSCs is strongly associated with a
      lower risk of prematurity complications including intraventricular hemorrhage,
      respiratory distress syndrome, infections, and anemia. The number of HSCs remains
      stable for the first six weeks of postnatal life. Besides, the number of CSPCs in
      CB is significantly higher in preterm infants than in full-term neonates (p <
      0.0001) and extensively decreases in preterm babies during next six weeks after
      birth. Finally, the growth of burst-forming unit of erythrocytes (BFU-E) and
      colony-forming units of granulocyte-macrophage (CFU-GM) obtained from CB of
      premature neonates is higher than those obtained from CB of full-term infants and
      strongly correlates with the number of CB-derived CSPCs. CONCLUSION: We conclude
      that CB HSCs are markedly associated with the development of premature birth
      complications. Thus, HSCs ought to be considered as the potential target for
      further research as they may be relevant for predicting and controlling the
      morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs
      circulating in CB are inversely associated with the birth weight of preterm
      infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal
      organism.

PMID- 22985191
TI  - Trace and label-free microRNA detection using oligonucleotide encapsulated silver
      nanoclusters as probes.
AB  - A simple, sensitive, and label-free method for microRNA (miRNA) biosensing was
      described using oligonucleotide encapsulated silver nanoclusters (Ag-NCs) as
      effective electrochemical probes. The functional oligonucleotide probe integrates
      both recognition sequence for hybridization and template sequence for in situ
      synthesis of Ag-NCs, which appears to possess exceptional metal mimic enzyme
      properties for catalyzing H(2)O(2) reduction. The miRNA assay employs gold
      electrodes to immobilize the molecular beacon (MB) probe. After the MB probe
      subsequently hybridizes with the target and functional probe, the oligonucleotide
      encapsulated Ag-NCs are brought to the electrode surface and produce a detection
      signal, in response to H(2)O(2) reduction. An electrochemical miRNA biosensor
      down to 67 fM with a linear range of 5 orders of magnitude was obtained.
      Meanwhile, the MB probe allows the biosensor to detect the target with high
      selectivity. The Ag-NCs-based approach provides a novel avenue to detect miRNA
      with high sensitivity and selectivity while avoiding laborious label and signal
      amplification. It is convinced that rational introduction of signal amplification
      strategy to the Ag-NCs-based bioanalysis can further improve the sensitivity. To
      our best knowledge, this is the first application of the electrocatalytic
      activity of Ag-NCs in bioanalysis, which would be attractive for genetic analysis
      and clinic biomedical application.

PMID- 22985190
TI  - Accuracy validation of adjuvant! online in Taiwanese breast cancer patients--a 10
      year analysis.
AB  - BACKGROUND: Adjuvant! Online ( http://www.adjuvantonline.com) is an Internet
      based software program that allows clinicians to make predictions about the
      benefits of adjuvant therapy and 10-year survival probability for early-stage
      breast cancer patients. This model has been validated in Western countries such
      as the United States, United Kingdom, Canada, Germany, and Holland. The aim of
      our study was to investigate the performance and accuracy of Adjuvant! Online in
      a cohort of Taiwanese breast cancer patients. METHODS: Data on the prognostic
      factors and clinical outcomes of 559 breast cancer patients diagnosed at the
      National Cheng Kung University Hospital in Tainan between 1992 and 2001 were
      enrolled in the study. Comprehensive demographic, clinical outcome data, and
      adjuvant treatment data were entered into the Adjuvant! Online program. The
      outcome prediction at 10 years was compared with the observed and predicted
      outcomes using Adjuvant! Online. RESULTS: Comparison between low- and high-risk
      breast cancer patient subgroups showed significant differences in tumor grading,
      tumor size, and lymph node status (p < 0.0001). The mean 10-year predicted death
      probability in 559 patients was 19.44%, and the observed death probability was
      15.56%. Comparison with the Adjuvant! Online-predicted breast cancer-specific
      survival (BCSS) showed significant differences in the whole cohort (p < 0.001).
      In the low-risk subgroup, the predicted and observed outcomes did not differ
      significantly (3.69% and 3.85%, respectively). In high-risk patients, Adjuvant!
      Online overestimated breast cancer-specific survival (p = 0.016); the predicted
      and observed outcomes were 21.99% and 17.46%, respectively. CONCLUSIONS:
      Adjuvant! Online accurately predicted 10-year outcomes and assisted in decision
      making about adjuvant treatment in low-risk breast cancer patients in our study,
      although the results were less accurate in the high-risk subgroup. Development of
      a prognostic program based on a national database should be considered,
      especially for high-risk breast cancer patients in Taiwan.

PMID- 22985192
TI  - Comparison between clinical, ultrasound, CT, MRI, and pathology findings in dogs
      presented for suspected thyroid carcinoma.
AB  - This study compares clinical, ultrasound, computed tomography (CT), magnetic
      resonance imaging (MRI), and pathology findings in 16 prospectively, and seven
      retrospectively recruited dogs presented for suspected thyroid carcinoma. Of
      these, 17 were confirmed thyroid carcinoma, while six were initially
      misdiagnosed. These included four carotid body tumors, one para-esophageal
      abscess, and one undifferentiated squamous cell carcinoma. Thyroid carcinomas
      occurred in older dogs without evidence of sex predilection, and were more often
      unilateral. All were large, heterogeneous, moderately to strongly vascularized,
      and most commonly contained areas of dystrophic mineralization and/or fluid
      accumulations. On MRI, thyroid carcinomas appeared hyperintense compared to
      surrounding musculature in all imaging sequences used, while on CT they had a
      lower attenuation value than normal thyroid gland tissue. Histologically
      confirmed tumor capsule disruption with invasion of the surrounding structures
      was most commonly detected with MRI. Palpation was not an accurate predictor of
      locally invasive vs. well-encapsulated masses. Computed tomography had the
      highest specificity (100%) and MRI had the highest sensitivity (93%) in
      diagnosing thyroid carcinoma, while ultrasound had considerably lower results. We
      conclude that ultrasound is adequate for use as a screening tool for dogs with
      suspected thyroid carcinoma, but recommend either CT or MRI for preoperative
      diagnosis and staging.

PMID- 22985193
TI  - Inhibition of the acquisition of conditioned place aversion by dopaminergic
      lesions of the central nucleus of the amygdala in morphine-treated rats.
AB  - The negative affective state of opiate abstinence plays an important role in
      craving and relapse to compulsive drug use. The dopamine system participates in
      the reward effects of opiate use and the aversive effect of opiate abstinence.
      The amygdala is an essential neural substrate for associative learning of
      emotion. To establish a model of conditioned place aversion (CPA) in morphine
      treated rats, we used different visual and tactual cues as conditioned stimuli
      (CS) within a conditioning apparatus. An injection of naloxone served as the
      unconditioned stimulus (US). The 6-hydroxydopamine (6-OHDA) lesion technique was
      used to investigate the effects of the dopaminergic system of the central nucleus
      of the amygdala (CeA) on naloxone-induced CPA. Rats were rendered physically
      dependent via administration of increasing doses of morphine delivered via
      intraperitoneal injection. Doses increased by 20 % each day for 14 days, starting
      from an initial dose of 6 mg/kg. All rats also received a low dose of naloxone
      (0.1 mg/kg) by injection 4 hours after morphine treatment on days 11 and 13 to
      induce CPA in a biased two-compartment conditioned place apparatus. Morphine
      dependent rats with sham lesions were found to develop significant CPA after
      naloxone treatment. Bilateral 6-OHDA lesions of the CeA impaired the acquisition
      of CPA but had no effect on locomotor activity. These results suggest that the
      dopaminergic system of the CeA plays an important role in the negative affective
      state of opiate abstinence.

PMID- 22985194
TI  - Unraveling the fluorescence features of individual corrole NH tautomers.
AB  - The fluorescence spectra of 10-(4,6-dichloropyrimidin-5-yl)-5,15-dimesitylcorrole
      have been studied in the temperature range from 4.2 to 332 K. For the first time,
      the individual fluorescence profiles of the two corrole NH tautomers have been
      assigned over the whole temperature range. The pronounced temperature dependence
      of the fluorescence spectra of the meso-pyrimidinylcorrole under study was found
      to originate from switching between the fluorescence emissions of the two
      tautomers due to a reduced NH tautomerization rate with decreasing temperature.
      As a result, the long wavelength tautomer dominates the total emission spectrum
      at room temperature, whereas at low temperatures, the majority of the emission
      comes from the short wavelength tautomer. Energy level diagrams (involving the
      two NH tautomers) explaining the excitation energy deactivation channels in the
      meso-pyrimidinylcorrole at room temperature and below are presented. A
      significant H/D isotope effect on the NH tautomerization rate has been observed,
      resulting in an enhanced contribution of the short wavelength tautomer to the
      total fluorescence spectrum at the expense of that of the long wavelength
      tautomer. Substantially different fluorescence quantum yields have been
      determined for the individual NH tautomers, leading to a pronounced temperature
      dependence of the overall fluorescence quantum yield. The obtained results allow
      the unambiguous statement that the two NH tautomers of corroles coexist in fluid
      and solid solutions in a wide range of temperatures, with the proportion
      depending on the corrole substitution pattern. Moreover, this study shows that
      the (future) interpretation of the fluorescence properties of meso
      pyrimidinylcorroles and all other corrole materials should be done (more)
      carefully, taking into account the coexistence of NH tautomers with individual
      spectral signatures.

PMID- 22985196
TI  - The influence of uncertain map features on risk beliefs and perceived ambiguity
      for maps of modeled cancer risk from air pollution.
AB  - Maps are often used to convey information generated by models, for example,
      modeled cancer risk from air pollution. The concrete nature of images, such as
      maps, may convey more certainty than warranted for modeled information. Three map
      features were selected to communicate the uncertainty of modeled cancer risk: (i)
      map contours appeared in or out of focus, (ii) one or three colors were used, and
      (iii) a verbal-relative or numeric risk expression was used in the legend. Study
      aims were to assess how these features influenced risk beliefs and the ambiguity
      of risk beliefs at four assigned map locations that varied by risk level. We
      applied an integrated conceptual framework to conduct this full factorial
      experiment with 32 maps that varied by the three dichotomous features and four
      risk levels; 826 university students participated. Data was analyzed using
      structural equation modeling. Unfocused contours and the verbal-relative risk
      expression generated more ambiguity than their counterparts. Focused contours
      generated stronger risk beliefs for higher risk levels and weaker beliefs for
      lower risk levels. Number of colors had minimal influence. The magnitude of risk
      level, conveyed using incrementally darker shading, had a substantial dose
      response influence on the strength of risk beliefs. Personal characteristics of
      prior beliefs and numeracy also had substantial influences. Bottom-up and top
      down information processing suggest why iconic visual features of incremental
      shading and contour focus had the strongest visual influences on risk beliefs and
      ambiguity. Variations in contour focus and risk expression show promise for
      fostering appropriate levels of ambiguity.

PMID- 22985195
TI  - Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic
      cell transplantation.
AB  - BACKGROUND AIMS: Anti-thymocyte globulin (ATG) is being used increasingly to
      prevent graft-versus-host disease (GvHD); however, its impact on immune
      reconstitution is relatively unknown. We (i) studied immune reconstitution after
      ATG-conditioned hematopoietic cell transplantation (HCT), (ii) determined the
      factors influencing the reconstitution, and (iii) compared it with non-ATG
      conditioned HCT. METHODS: Immune cell subset counts were determined at 1-24
      months post-transplant in 125 HCT recipients who received ATG during
      conditioning. Subset counts were also determined in 46 non-ATG-conditioned
      patients (similarly treated). RESULTS: (i) Reconstitution after ATG-conditioned
      HCT was fast for innate immune cells, intermediate for B cells and CD8 T cells,
      and very slow for CD4 T cells and invariant natural killer T (iNKT) (iNKT) cells.
      (ii) Faster reconstitution after ATG-conditioned HCT was associated with a higher
      number of cells of the same subset transferred with the graft in the case of
      memory B cells, naive CD4 T cells, naive CD8 T cells, iNKT cells and myeloid
      dendritic cells; lower recipient age in the case of naive CD4 T cells and naive
      CD8 T cells; cytomegalovirus recipient seropositivity in the case of
      memory/effector T cells; an absence of GvHD in the case of naive B cells; lower
      ATG serum levels in the case of most T-cell subsets, including iNKT cells; and
      higher ATG levels in the case of NK cells and B cells. (iii) Compared with non
      ATG-conditioned HCT, reconstitution after ATG-conditioned HCT was slower for CD4
      T cells, and faster for NK cells and B cells. CONCLUSIONS: ATG worsens the
      reconstitution of CD4 T cells but improves the reconstitution of NK and B cells.

PMID- 22985197
TI  - Stomatal penetration by aqueous solutions--an update involving leaf surface
      particles.
AB  - The recent visualization of stomatal nanoparticle uptake ended a 40-yr-old
      paradigm. Assuming clean, hydrophobic leaf surfaces, the paradigm considered
      stomatal liquid water transport to be impossible as a result of water surface
      tension. However, real leaves are not clean, and deposited aerosols may change
      hydrophobicity and water surface tension. Droplets containing NaCl, NaClO(3),
      (NH(4))(2) SO(4), glyphosate, an organosilicone surfactant or various
      combinations thereof were evaporated on stomatous abaxial and astomatous adaxial
      surfaces of apple (Malus domestica) leaves. The effects on photosynthesis,
      necrosis and biomass were determined. Observed using an environmental scanning
      electron microscope, NaCl and NaClO(3) crystals on hydrophobic tomato (Solanum
      lycopersicum) cuticles underwent several humidity cycles, causing repeated
      deliquescence and efflorescence of the salts. All physiological parameters were
      more strongly affected by abaxial than adaxial treatments. Spatial expansion and
      dendritic crystallization of the salts occurred and cuticular hydrophobicity was
      decreased more rapidly by NaClO(3) than NaCl. The results confirmed the stomatal
      uptake of aqueous solutions. Humidity fluctuations promote the spatial expansion
      of salts into the stomata. The ion-specific effects point to the Hofmeister
      series: chaotropic ions reduce surface tension, probably contributing to the
      defoliant action of NaClO(3), whereas the salt spray tolerance of coastal plants
      is probably linked to the kosmotropic nature of chloride ions.

PMID- 22985199
TI  - Long-range temporal correlations in the subthalamic nucleus of patients with
      Parkinson's disease.
AB  - Neuronal activity in the subthalamic nucleus (STN) of patients with Parkinson's
      disease (PD) is characterised by excessive neuronal synchronization, particularly
      in the beta frequency range. However, less is known about the temporal dynamics
      of neuronal oscillations in PD. In this respect long-range temporal correlations
      (LRTC) are of special interest as they quantify the neuronal dynamics on
      different timescales and have been shown to be relevant for optimal information
      processing in the brain. While the presence of LRTC has been demonstrated in
      cortical data, their existence in deep brain structures remains an open question.
      We investigated (i) whether LRTC are present in local field potentials (LFP)
      recorded bilaterally from the STN at wakeful rest in ten patients with PD after
      overnight withdrawal of levodopa (OFF) and (ii) whether LRTC can be modulated by
      levodopa treatment (ON). Detrended fluctuation analysis was utilised in order to
      quantify the temporal dynamics in the amplitude fluctuations of LFP oscillations.
      We demonstrated for the first time the presence of LRTC (extending up to 50 s) in
      the STN. Importantly, the ON state was characterised by significantly stronger
      LRTC than the OFF state, both in beta (13-35 Hz) and high-frequency (> 200 Hz)
      oscillations. The existence of LRTC in subcortical structures such as STN
      provides further evidence for their ubiquitous nature in the brain. The weaker
      LRTC in the OFF state might indicate limited information processing in the
      dopamine-depleted basal ganglia. The present results implicate LRTC as a
      potential biomarker of pathological neuronal processes in PD.

PMID- 22985198
TI  - Copper-catalyzed recycling of halogen activating groups via 1,3-halogen
      migration.
AB  - A Cu(I)-catalyzed 1,3-halogen migration reaction effectively recycles an
      activating group by transferring bromine or iodine from a sp(2) to a benzylic
      carbon with concomitant borylation of the Ar-X bond. The resulting benzyl halide
      can be reacted in the same vessel under a variety of conditions to form an
      additional carbon-heteroatom bond. Cross-over experiments using an isotopically
      enriched bromide source support intramolecular transfer of Br. The reaction is
      postulated to proceed via a Markovnikov hydrocupration of the o-halostyrene,
      oxidative addition of the resulting Cu(I) complex into the Ar-X bond, reductive
      elimination of the new sp(3) C-X bond, and final borylation of an Ar-Cu(I)
      species to turn over the catalytic cycle.

PMID- 22985201
TI  - Exclamation marks and other trichoscopic signs of chemotherapy-induced alopecia.

PMID- 22985202
TI  - Right ventricular function predicts clinical response to specific vasodilator
      therapy in patients with pulmonary hypertension.
AB  - INTRODUCTION: We followed patients with pulmonary arterial hypertension (PAH)
      receiving specific vasodilator therapy and tested for predictors of clinical
      outcome. METHODS: Thirty-two patients (mean age 39 +/- 15 years, 22 women,
      diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with
      inoperable chronic thromboembolic PH received therapy with either bosentan,
      sildenafil, or both and were evaluated with clinical parameters, biomarkers (B
      type natriuretic peptide values), and echocardiography before receiving specific
      medication and every 3 months thereafter. A right heart catheterization was
      performed at baseline. A composite endpoint of death, worsening of functional
      class, or the need of a second vasodilator agent was used to define the clinical
      nonresponders. RESULTS: Patients were followed for 14 months (7.5-21). The
      endpoint was reached by 15 patients: four patients died (two idiopathic PAH and
      two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional
      class worsening, and four patients needed to be switched to combination therapy.
      Patients who remained clinically stable or improved had at baseline a better
      cardiac output with a less remodeled right ventricle (RV) and better functioning
      RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV
      global strain value higher than -13.4% predict with 87% sensitivity and 83%
      specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC
      84.2%, P = 0.003), respectively, patients who will deteriorate clinically under
      specific vasodilator therapy. A multivariate model showed RVFAC to be the only
      independent predictor of the endpoint with a HR of 0.87 (0.8-0.96), P = 0.007.
      CONCLUSIONS: Over an average period of 1 year, almost half of patients showed
      signs of clinical deterioration despite specific vasodilator therapy. Parameters
      of right ventricular morphology and function had prognostic value in these
      patients.

PMID- 22985203
TI  - Enhanced mineralization of diuron using a cyclodextrin-based bioremediation
      technology.
AB  - The phenylurea herbicide diuron [N-(3,4-dichlorophenyl)-N,N-dimethylurea] is
      widely used in a broad range of herbicide formulations and, consequently, it is
      frequently detected as a major soil and water contaminant in areas where there is
      extensive use. Diuron has the unfortunate combination of being strongly adsorbed
      by soil organic matter particles and, hence, slowly degraded in the environment
      due to its reduced bioavailability. N-Phenylurea herbicides seem to be
      biodegraded in soil, but it must be kept in mind that this biotic or abiotic
      degradation could lead to accumulation of very toxic derived compounds, such as
      3,4-dichloroaniline. Research was conducted to find procedures that might result
      in an increase in the bioavailability of diuron in contaminated soils, through
      solubility enhancement. For this purpose a double system composed of
      hydroxypropyl-beta-cyclodextrin (HPBCD), which is capable of forming inclusion
      complexes in solution, and a two-member bacterial consortium formed by the diuron
      degrading Arthrobacter sulfonivorans (Arthrobacter sp. N2) and the linuron
      degrading Variovorax soli (Variovorax sp. SRS16) was used. This consortium can
      achieve a complete biodegradation of diuron to CO2 with regard to that observed
      in the absence of the CD solution, where only a 45% biodegradation was observed.
      The cyclodextrin-based bioremediation technology here described shows for the
      first time an almost complete mineralization of diuron in a soil system, in
      contrast to previous incomplete mineralization based on single or consortium
      bacterial degradation. 

PMID- 22985204
TI  - Treatment monitoring and mortality risk adjustment in anaemic Jehovah's
      Witnesses.
AB  - BACKGROUND: Management of anaemic Jehovah's Witness (JW) patients, who refuse
      blood transfusion on religious grounds, is challenging. In the published
      literature, there are few cohort studies that consider causes of mortality in
      isolation and are lacking in their predictive power. This does not allow
      clinicians to monitor treatment progress of severely anaemic JW patients and
      adjust their risk of mortality. The study aims to develop an anaemia-related
      mortality risk prediction instrument. METHODS: This retrospective cohort study
      evaluated anaemia-related mortality risk factors of JW patients. JW patients were
      identified from the records of four major public hospitals in the Auckland and
      Midlands regions of New Zealand (North Shore, Auckland City, Middlemore and
      Waikato hospitals) for the period 1998 to 2007 inclusive. The inclusion criteria
      were age >=15 years and severe anaemia (haemoglobin concentration <=80 g/L).
      Palliative care cancer patients were excluded. RESULTS: Anaemia-related risk
      factors of mortality for JW patients were identified, weighted and used to
      construct a mortality risk predictive score (the Hamilton Anaemia Mortality Risk
      Score (Hamilton AMRS)). This permitted stratification of JW patients into
      mortality risk groups according to their Hamilton AMRS. It is shown that patients
      with Hamilton AMRS of 0 to 2 had 4% mortality, patients with Hamilton AMRS of 3
      to 4 had 29% mortality, patients with Hamilton AMRS of 5 had 40% mortality and
      patients with Hamilton AMRS of >=6 had 67% mortality. CONCLUSION: The Hamilton
      AMRS allows treatment monitoring of anaemic JW patients and adjustment of their
      risk of mortality.

PMID- 22985205
TI  - 12-month follow-up of fluoxetine and cognitive behavioral therapy for binge
      eating disorder.
AB  - OBJECTIVE: The longer term efficacy of medication treatments for binge-eating
      disorder (BED) remains unknown. This study examined the longer term effects of
      fluoxetine and cognitive behavioral therapy (CBT) either with fluoxetine (CBT +
      fluoxetine) or with placebo (CBT + placebo) for BED through 12-month follow-up
      after completing treatments. METHOD: 81 overweight patients with BED within a
      randomized double-blind placebo-controlled acute treatment trial allocated to
      fluoxetine-only, CBT + fluoxetine, and CBT + placebo were assessed before
      treatment, during treatment, posttreatment, and 6 and 12 months after completing
      treatments. Outcome variables comprised remission from binge eating (0 binge
      eating episodes for 28 days) and continuous measures of binge-eating frequency,
      eating disorder psychopathology, depression, and weight. RESULTS: Intent-to-treat
      remission rates (missing data coded as nonremission) differed significantly
      across treatments at posttreatment and at 6- and 12-month follow-ups. At 12-month
      follow-up remission rates were 3.7% for fluoxetine-only, 26.9% for CBT +
      fluoxetine, and 35.7% for CBT + placebo. Mixed-effects models of all available
      continuous data (without imputation) at posttreatment and at 6- and 12-month
      follow-ups (controlling for baseline scores) revealed the treatments differed on
      all clinical outcome variables, except for weight, across time. CBT + fluoxetine
      and CBT + placebo did not differ and both were significantly superior to
      fluoxetine-only on the majority of clinical outcomes. CONCLUSIONS: This
      represents the first report from any randomized placebo-controlled trial for BED
      that has reported follow-up data after completing a course of medication-only
      treatment. CBT + placebo was superior to fluoxetine-only, and adding fluoxetine
      to CBT did not enhance findings compared to adding placebo to CBT. The findings
      document the longer term effectiveness of CBT, but not fluoxetine, through 12
      months after treatment completion.

PMID- 22985207
TI  - Comparison of buccal and nasal dexmedetomidine premedication for pediatric
      patients.
AB  - BACKGROUND: Alpha-2 adrenergic agonists are used to premedicate pediatric
      patients to reduce separation anxiety and achieve calm induction. The clinical
      effects of clonidine are similar whether via the oral or nasal route. However,
      oral dexmedetomidine is not preferred because of its poor bioavailability. The
      objective of this study was to evaluate the effects of nasal versus buccal
      dexmedetomidine used for premedication in children. METHODS: Sixty-two patients,
      aged 2-6 years, undergoing minor elective surgery were randomly assigned to two
      groups to receive dexmedetomidine, either 1 MUg.kg(-1) buccally (group B) or 1
      MUg.kg(-1) intranasally (group N) for premedication 45 min before the induction
      of anesthesia. Heart rate, peripheral oxygen saturation, and respiratory rate
      were measured before and every 10 min after administering dexmedetomidine in all
      children. Level of sedation was assessed every 10 min until transport to
      operating room. Drug acceptance, parental separation, and face mask acceptance
      scores were recorded. RESULTS: There was no significant difference between the
      two groups in patient characteristics, nor was there any significant difference
      between the two groups in heart rate, respiratory rate, or SpO(2) values at all
      times after premedication. Levels of sedation, parental separation, and mask
      acceptance scores were significantly higher in group N than in group B at the
      various times. CONCLUSIONS: These results suggest that intranasal administration
      of 1 MUg.kg(-1) dexmedetomidine is more effective than buccal administration of 1
      MUg.kg(-1) dexmedetomidine for premedication in children.

PMID- 22985208
TI  - Diameter-dependent surface photovoltage and surface state density in single
      semiconductor nanowires.
AB  - Based on single-nanowire surface photovoltage measurements and finite-element
      electrostatic simulations, we determine the surface state density, N(s), in
      individual n-type ZnO nanowires as a function of nanowire diameter. In general,
      N(s) increases as the diameter decreases. This identifies an important origin of
      the recently reported diameter dependence of the surface recombination velocity,
      which has been commonly considered to be independent of the diameter.
      Furthermore, through the determination of the surface carrier lifetime, we
      suggest that the diameter dependence of the surface state density accounts for
      the rather abrupt transition from bulk-limited to surface-limited carrier
      transport over a narrow nanowire diameter regime (~30-40 nm). These findings are
      supported by the comparison between bulk-limited and surface-dependent minority
      carrier diffusion lengths measured at various diameters.

PMID- 22985206
TI  - Global endometrial transcriptomic profiling: transient immune activation precedes
      tissue proliferation and repair in healthy beef cows.
AB  - BACKGROUND: All cows experience bacterial contamination and tissue injury in the
      uterus postpartum, instigating a local inflammatory immune response. However
      mechanisms that control inflammation and achieve a physiologically functioning
      endometrium, while avoiding disease in the postpartum cow are not succinctly
      defined. This study aimed to identify novel candidate genes indicative of
      inflammation resolution during involution in healthy beef cows. Previous
      histological analysis of the endometrium revealed elevated inflammation 15 days
      postpartum (DPP) which was significantly decreased by 30 DPP. The current study
      generated a genome-wide transcriptomic profile of endometrial biopsies from these
      cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq
      identified KEGG pathways enriched by significantly differentially expressed genes
      at both time points. Novel candidate genes associated with inflammatory
      resolution were subsequently validated in additional postpartum animals using
      quantitative real-time PCR (qRT-PCR). RESULTS: mRNA-Seq revealed 1,107
      significantly differentially expressed genes, 73 of which were increased 15 DPP
      and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways
      (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus
      host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP,
      where the majority of genes were differentially expressed, the enrichment
      (adjusted P < 0.1) of tissue repair and proliferative activity pathways was
      observed. Nineteen candidate genes selected from mRNA-Seq results, were
      independently assessed by qRT-PCR in additional postpartum cows (5 animals) at
      both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were
      significantly elevated 30 DPP and are functionally associated with tissue repair
      and the restoration of uterine homeostasis postpartum. CONCLUSIONS: The results
      of this study reveal an early activation of the immune response which undergoes a
      temporal functional change toward tissue proliferation and regeneration during
      endometrial involution in healthy postpartum cows. These molecular changes mirror
      the activation and resolution of endometrial inflammation during involution
      previously classified by the degree of neutrophil infiltration. SAA1/2, GATA2,
      IGF1, SHC2, and SERPINA14 genes may become potential markers for resolution of
      endometrial inflammation in the postpartum cow.

PMID- 22985209
TI  - Infection relapse in spondyloarthritis treated with biological drugs: a single
      centre study.

PMID- 22985210
TI  - Polyaniline stabilized magnetite nanoparticle reinforced epoxy nanocomposites.
AB  - Magnetic epoxy polymer nanocomposites (PNCs) reinforced with magnetite
      (Fe(3)O(4)) nanoparticles (NPs) have been prepared at different particle loading
      levels. The particle surface functionality tuned by conductive polyaniline (PANI)
      is achieved via a surface initiated polymerization (SIP) approach. The effects of
      nanoparticle loading, surface functionality, and temperature on both the
      viscosity and storage/loss modulus of liquid epoxy resin suspensions and the
      physicochemical properties of the cured solid PNCs are systematically
      investigated. The glass transition temperature (T(g)) of the cured epoxy filled
      with the functionalized NPs has shifted to the higher temperature in the dynamic
      mechanical analysis (DMA) compared with that of the cured pure epoxy. Enhanced
      mechanical properties of the cured epoxy PNCs filled with the functionalized NPs
      are observed in the tensile test compared with that of the cured pure epoxy and
      cured epoxy PNCs filled with as-received NPs. The uniform NP distribution in the
      cured epoxy PNCs filled with functionalized NPs is observed by scanning electron
      microscope (SEM). These magnetic epoxy PNCs show the good magnetic properties and
      can be attached by a permanent magnet. Enhanced interfacial interaction between
      NPs and epoxy is revealed in the fracture surface analysis. The PNCs formation
      mechanism is also interpreted from the comprehensive analysis based on the TGA,
      DSC, and FTIR in this work.

PMID- 22985211
TI  - Comparative secretome analyses using a hollow fiber culture system with label
      free quantitative proteomics indicates the influence of PARK7 on cell
      proliferation and migration/invasion in lung adenocarcinoma.
AB  - As the leading cause of cancer death worldwide, lung cancer lacks effective
      diagnosis tools and treatments to prevent its metastasis. Fortunately, secretome
      has clinical usages as biomarkers and protein drugs. To discover the secretome
      that influences lung adenocarcinoma metastasis, the hollow fiber culture (HFC)
      system was used along with label-free proteomics approach to analyze cell
      secretomes between CL1-0 and CL1-5 cell lines, which exhibit low and high
      metastatic potentials. Among the 703 proteins quantified, 50 possessed different
      levels between CL1-0 and CL1-5. PARK7 was a primary focus because of the lack of
      research involving lung adenocarcinoma. The cell proliferation, migration, and
      invasion properties of CL1-0, CL1-5, and A549 cells were significantly diminished
      when the expression of their PARK7 proteins was reduced. Conversely, these
      functions were promoted when PARK7 was overexpressed in CL1-0. In clinical
      expression, PARK7 levels within tissue specimens and plasma samples were
      significantly higher in the cancer group. This represents the first time the HFC
      system has been used with label-free quantification to discern the elements of
      metastasis in lung adenocarcinoma cell secretomes. Likewise, PARK7 has never been
      researched for its role in promoting lung adenocarcinoma progression.

PMID- 22985212
TI  - New Aspects on the Mechanism of C3H6 selective catalytic reduction of NO in the
      presence of O2 over LaFe1-x(Cu, Pd)xO3-delta perovskites.
AB  - A series of LaFe(1-x)(Cu, Pd)(x)O(3-delta) perovskites was fully characterized
      and tested for the selective catalytic reduction (SCR) of NO by C(3)H(6) in the
      presence of O(2). The adsorbed species and surface reactions were investigated
      for mechanistic study by means of NO-temperature-programmed desorption (TPD),
      C(3)H(6)/O(2)-TPD, and in situ diffuse reflectance Fourier transform
      spectroscopy, in order to discriminate the effects of copper and palladium
      partial substitutions. With respect to LaFeO(3), Cu(2+) incorporation obviously
      improved SCR performance, due to its properties for C(3)H(6) activation with an
      easy generation of partially oxidized active surface C(x)H(y)O(z) species. The
      excellent catalytic activity at the low temperatures over LaFe(0.94)Pd(0.06)O(3)
      was attributed to the formation of reactive nitrites/nitrates, leading to a rapid
      reaction between adNO(x) and C(x)H(y)O(z) species, as well as a decreased
      occupation of the active sites by the inactive ionic nitrates. A mechanism was
      herein proposed with the formation of nitrite/nitrate and C(x)H(y)O(z) surface
      species and the further organo nitrogen compounds (ONCs)/-CN/-NCO as important
      intermediates. Moreover, the acceleration of both formation of inactive ionic
      nitrate and deep oxidation of C(3)H(6) contributed to a negative effect of O(2)
      excess for NO reduction, while Pd substitution significantly increased the O(2)
      tolerance ability.

PMID- 22985213
TI  - Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo,
      all in combination with metformin in type 2 diabetes: 2-year results from the
      LEAD-2 study.
AB  - AIMS: To investigate efficacy and safety of dual therapy with liraglutide and
      metformin in comparison to glimepiride and metformin, and metformin monotherapy
      over 2 years in patients with type 2 diabetes. METHODS: In the 26-week the
      Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n =
      1091) were randomized (2 : 2 : 2 : 1: 2) to liraglutide (0.6, 1.2 or 1.8 mg once
      daily), placebo or glimepiride; all with metformin. Patients were enrolled if
      they were 18-80 years old with HbA1c 7.0-11.0% (previous monotherapy >=3 months),
      or 7.0-10.0% (previous combination therapy >=3 months), and body mass index <=40
      kg/m(2) . Patients completing the 26-week double-blinded phase could enter an 18
      month open-label extension. RESULTS: HbA1c decreased significantly with
      liraglutide (0.4% with 0.6 mg, 0.6% with 1.2 and 1.8 mg) versus 0.3% increase
      with metformin monotherapy (p < 0.0001). HbA1c decrease with liraglutide was non
      inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced
      significant weight loss (2.1, 3.0 and 2.9 kg with 0.6, 1.2 and 1.8 mg,
      respectively) compared to weight gain (0.7 kg) with glimepiride (p < 0.0001).
      Weight loss with liraglutide 1.2 and 1.8 mg was significantly greater than with
      metformin monotherapy (1.8 kg; p = 0.0185 and p = 0.0378 for 1.2 and 1.8 mg,
      respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide
      groups, significantly less than with glimepiride (24.0%; p < 0.0001). Liraglutide
      was well tolerated overall: gastrointestinal events were more common than with
      glimepiride or metformin monotherapy, but occurrence decreased with time.
      CONCLUSIONS: Liraglutide provided sustained glycaemic control over 2 years
      comparable to that provided by glimepiride. Liraglutide was well tolerated, and
      was associated with weight loss and a low rate of hypoglycaemia.

PMID- 22985214
TI  - Accumulation of cellobiose lipids under nitrogen-limiting conditions by two
      ustilaginomycetous yeasts, Pseudozyma aphidis and Pseudozyma hubeiensis.
AB  - Some basidiomycetous yeast strains extracellularly produce cellobiose lipids
      (CLs), glycolipid biosurfactants which have strong fungicidal activity. The
      representative CL producer Ustilago maydis produces CLs together with the other
      glycolipids, mannosylerythritol lipids (MELs); the preference of the two
      glycolipids is affected considerably by the nitrogen source. To develop new CL
      producers, 12 MEL producers were cultured under the nitrogen-limited conditions.
      Pseudozyma aphidis and Pseudozyma. hubeiensis were characterized as new CL
      producers. CL production was induced on three strains, P. aphidis, Pseudozyma
      graminicola, and P. hubeiensis under these conditions. The putative homologous
      genes of U. maydis cyp1, which encodes a P450 monooxygenase, essential for CL
      biosynthesis, were partially amplified from their genomic DNA. The nucleotide
      sequences of the gene fragments from P. hubeiensis and P. aphidis shared
      identities with U. maydis cyp1 of 99% and 78%, respectively. Furthermore, all of
      the deduced translation products are tightly clustered in the phylogenic tree of
      the monooxygenase. These results suggest that the genes involved with CL
      biosynthesis must be widely distributed in the basidiomycetous fungi as well as
      the MEL biosynthesis genes, and thus, the genus Pseudozyma has great potential as
      a biosurfactant producer.

PMID- 22985215
TI  - Evaluation of the gastrointestinal tract in dogs using computed tomography.
AB  - Abdominal computed tomography (CT) studies of 19 dogs with no history or clinical
      signs of gastrointestinal disease, and two dogs with a histological diagnosis of
      gastrointestinal neoplasia were examined retrospectively. Gastrointestinal
      segments were evaluated subjectively for conspicuity, contrast enhancement, and
      wall layering after contrast medium administration. In dogs without
      gastrointestinal disease, there were 62.8% of gastrointestinal segments (serosa
      to serosa) and 77.7% of gastrointestinal walls (serosa to mucosa) visualized.
      Wall layering on postcontrast images was seen in 21.8% of gastrointestinal
      segments. There was significant association between gastrointestinal diameter and
      wall thickness. There was significant association between weight and
      gastrointestinal wall thickness in the following regions: gastric fundus, gastric
      body, gastric pylorus, gastric pyloric antrum, duodenal cranial flexure, jejunum
      and ascending colon, and between patient weight and gastrointestinal diameter in
      cranial duodenal flexure, descending duodenum, transverse duodenum, ascending
      duodenum, and jejunum. Measurements acquired from CT studies correlated well with
      previously published normal reference ranges for radiographic and
      ultrasonographic studies. Gastrointestinal neoplasia, diagnosed in two dogs, had
      a gastrointestinal wall thickness greater than the range of the dogs without
      gastrointestinal disease. Computed tomography offers identification of the
      gastrointestinal tract segments in dogs, allows for evaluation of
      gastrointestinal diameter and aids in investigation of gastrointestinal wall
      thickness.

PMID- 22985216
TI  - H-shaped supra-amphiphiles based on a dynamic covalent bond.
AB  - The imine bond, a kind of dynamic covalent bond, is used to bind two bolaform
      amphiphiles together with spacers, yielding H-shaped supra-amphiphiles. Micellar
      aggregates formed by the self-assembly of the H-shaped supra-amphiphiles are
      observed. When pH is tuned down from basic to slightly acidic, the benzoic imine
      bond can be hydrolyzed, leading to the dissociation of H-shaped supra
      amphiphiles. Moreover, H-shaped supra-amphiphiles have a lower critical micelle
      concentration than their building blocks, which is very helpful in enhancing the
      stability of the benzoic imine bond being hydrolyzed by acid. The surface tension
      isotherms of the H-shaped supra-amphiphiles with different spacers indicate their
      twisty conformation at a gas-water interface. The study of H-shaped supra
      amphiphiles can enrich the family of amphiphiles, and moreover, the pH
      responsiveness may make them apply to controlled or targetable drug delivery in a
      biological environment.

PMID- 22985217
TI  - Prevalence and predictors of selenium and vitamin E supplementation in a urology
      population.
AB  - OBJECTIVES: Preclinical and epidemiological studies have suggested the use of
      supplements such as selenium and vitamin E for prostate cancer (PCa) prevention;
      however, clinical trials have not demonstrated clear benefit in patients. This
      study aims to investigate the current prevalence and predictors for use of these
      supplements in men in a urology population. DESIGN, SUBJECTS, AND OUTCOMES
      MEASURED: Three hundred and twelve (312) men visiting the Princess Margaret
      Hospital Ambulatory Urology Clinic were enrolled in this University Health
      Network Research Ethics Board-approved questionnaire-based study investigating
      supplement use, reasons for use and demographic characteristics. RESULTS: It was
      observed that 13.5% and 20.8% of the participants are currently using selenium
      and vitamin E, respectively, while 10.6% and 15.7% previously used selenium and
      vitamin E, respectively. Both education (percentage of users comparing less than
      college education versus college or above education: selenium: 14% versus 28%;
      p=0.008, vitamin E: 26% versus 41%; p=0.013) and health literacy (mean scores+/
      standard error of the mean of users versus nonusers: selenium question 1:
      1.4507+/-0.09576 versus 1.6083+/-0.07211; p=0.023, selenium question 2: 2.8750+/
      0.04395 versus 2.7106+/-0.03774; p=0.000, selenium question 3: 1.4583+/-0.08377
      versus 1.7064+/-0.06278; p=0.025, vitamin E question 1: 2.8036+/-0.04545 versus
      2.7179+/-0.04097; p=0.010, vitamin E question 2: 1.5446+/-0.06698 versus 1.7077+/
      0.07241; p=0.006) are predictors of selenium and vitamin E use on univariable
      analysis. On multivariable analysis education (selenium odds ratio=2.095, 95%
      confidence interval=1.019-4.305, p=0.044; vitamin E odds ratio=1.855, 95%
      confidence interval=1.015-3.338, p=0.045) remains a significant predictor of
      selenium and vitamin E use. Examining the data on use by education, it was found
      that more men with a higher education attributed their use of selenium to
      urologist advice (24%), and those with a lower education attributed their use of
      selenium to naturopath/homeopath advice (28%). CONCLUSIONS: Many men who visit
      urology clinics use selenium and vitamin E despite the lack of clinical support
      for chemoprevention. Education and health literacy are important variables in
      determining the use of these supplements in these men. This information may aid
      in addressing the needs of the diverse patient population using these supplements
      for the prevention of PCa.

PMID- 22985218
TI  - Effects of Tai Chi Exercise on glucose control, neuropathy scores, balance, and
      quality of life in patients with type 2 diabetes and neuropathy.
AB  - PURPOSE: The aim of this study was to determine the effects of Tai Chi exercise
      on glucose control, neuropathy scores, balance, and quality of life in patients
      with type 2 diabetes and neuropathy. METHODS: A pretest-posttest design with a
      nonequivalent control group was utilized to recruit 59 diabetic patients with
      neuropathy from an outpatient clinic of a university hospital. A standardized Tai
      Chi for diabetes program was provided, which comprised 1 hour of Tai Chi per
      session, twice a week for 12 weeks. Outcome variables were fasting blood glucose
      and glycosylated hemoglobin for glucose control, the Semmes-Weinstein 10-g
      monofilament examination scores and total symptom scores for neuropathy, single
      leg stance for balance, and the Korean version of the SF-36v2 for quality of
      life. Thirty-nine patients completed the posttest measures after the 12-week Tai
      Chi intervention, giving a 34% dropout rate. RESULTS: The mean age of the
      participants was 64 years, and they had been diagnosed with type 2 diabetes for
      more than 12 years. The status was significantly better for the participants in
      the Tai Chi group (n=20) than for their control (i.e., nonintervention)
      counterparts (n=19) in terms of total symptom scores, glucose control, balance,
      and quality of life. CONCLUSION: Tai Chi improved glucose control, balance,
      neuropathic symptoms, and some dimensions of quality of life in diabetic patients
      with neuropathy. Further studies with larger samples and long-term follow-up are
      needed to confirm the effects of Tai Chi on the management of diabetic
      neuropathy, which may have an impact on fall prevention in this population.

PMID- 22985220
TI  - The LINKIN Health Census process: design and implementation.
AB  - This paper describes the first phase of the LINKIN Health Study, which aims to
      evaluate health system functioning within a rural population. Locally relevant
      data on the health status and service usage of this population, including non
      users and users, health service providers traditionally omitted from health
      services research, and multiple socio-economic indicators, was collected using a
      self-complete health census. Household response was 75% (N = 4425). Response was
      greater when face-to-face contact was made at delivery compared to when
      questionnaires were left in the letterbox (89% vs 64%), falling to 26% when no
      face-to-face contact was made at either delivery or collection.

PMID- 22985219
TI  - First growth curves based on the World Health Organization reference in a
      Nationally-Representative Sample of Pediatric Population in the Middle East and
      North Africa (MENA): the CASPIAN-III study.
AB  - BACKGROUND: The World Health Organization (WHO) is in the process of establishing
      a new global database on the growth of school children and adolescents. Limited
      national data exist from Asian children, notably those living in the Middle East
      and North Africa (MENA). This study aimed to generate the growth chart of a
      nationally representative sample of Iranian children aged 10-19 years, and to
      explore how well these anthropometric data match with international growth
      references. METHODS: In this nationwide study, the anthropometric data were
      recorded from Iranian students, aged 10-19 years, who were selected by multistage
      random cluster sampling from urban and rural areas. Prior to the analysis,
      outliers were excluded from the features height-for-age and body mass index (BMI)
      for-age using the NCHS/WHO cut-offs. The Box-Cox power exponential (BCPE) method
      was used to calculate height-for-age and BMI-for-age Z-scores for our study
      participants. Then, children with overweight, obesity, thinness, and severe
      thinness were identified using the BMI-for-age z-scores. Moreover, stunted
      children were detected using the height-for-age z-scores. The growth curve of the
      Iranian children was then generated from the z-scores, smoothed by cubic S
      plines. RESULTS: The study population comprised 5430 school students consisting
      of 2312 (44%) participants aged 10-14 years , and 3118 (58%) with 15-19 years of
      age. Eight percent of the participants had low BMI (thinness: 6% and severe
      thinness: 2%), 20% had high BMI (overweight: 14% and obesity: 6%), and 7% were
      stunted. The prevalence rates of low and high BMI were greater in boys than in
      girls (P < 0.001). The mean BMI-for-age, and the average height-for-age of
      Iranian children aged 10-19 years were lower than the WHO 2007 and United states
      Centers for Disease Control and Prevention 2000 (USCDC2000) references.
      CONCLUSIONS: The current growth curves generated from a national dataset may be
      included for establishing WHO global database on children's growth. Similar to
      most low-and middle income populations, Iranian children aged 10-19 years are
      facing a double burden of weight disorders, notably under- and over- nutrition,
      which should be considered in public health policy-making.

PMID- 22985221
TI  - Solvent-dependent deprotonation of meso-pyrimidinylcorroles: absorption and
      fluorescence studies.
AB  - The absorption spectra of 10-(4,6-dichloropyrimidin-5-yl)-5,15-dimesitylcorrole
      have been studied in 15 solvents. The formation of deprotonated corrole species
      was found to account for the dramatic changes in the absorption spectra in
      several solvents. Careful analysis of the relationship between the formation of
      deprotonated species and solvent properties results in the conclusion that there
      is no single solvent parameter correlation, and either multiparameter
      correlations or specific solute-solvent interactions (preferential solvation of
      the most acidic NH tautomer or perturbation of intramolecular hydrogen bonding in
      the macrocycle core) should be considered. The fluorescence properties of the
      deprotonated pyrimidinylcorrole are also reported for the first time and compared
      to those of free-base and protonated species.

PMID- 22985222
TI  - Method for comparative analysis of ribonucleic acids using isotope labeling and
      mass spectrometry.
AB  - Here, we describe a method for the comparative analysis of ribonucleic acids
      (RNAs). This method allows sequence or modification information from a previously
      uncharacterized RNA to be obtained by direct comparison with a reference RNA,
      whose sequence or modification information is known. This simple and rapid method
      is enabled by the differential labeling of two RNA samples. One sample, the
      reference RNA, is labeled with (16)O during enzymatic digestion. The second
      sample, the candidate or unknown RNA, is labeled with (18)O. By combining the two
      digests, digestion products that share the same sequence or post-transcriptional
      modification(s) between the reference and candidate will appear as doublets
      separated by 2 Da. Sequence or modification differences between the two will
      generate singlets that can be further characterized to identify how the candidate
      sequence differs from the reference. We illustrate the application of this
      approach for sequencing individual RNAs and demonstrate how this method can be
      used to identify sequence-specific differences in RNA modification. This
      comparative analysis of RNA digests (CARD) approach is scalable to multiple
      candidate RNAs using one or multiple reference RNAs and is compatible with
      existing methods for quantitative analysis of RNAs.

PMID- 22985223
TI  - Tunable mid-infrared localized surface plasmon resonances in silicon nanowires.
AB  - We observe and systematically tune an intense mid-infrared absorption mode that
      results from phosphorus doping in silicon nanowires synthesized via the vapor
      liquid-solid technique. The angle- and shape-dependence of this spectral feature,
      as determined via in-situ transmission infrared spectroscopy, supports its
      assignment as a longitudinal localized surface plasmon resonance (LSPR).
      Modulation of resonant frequency (740-1620 cm(-1)) is accomplished by varying
      nanowire length (135-1160 nm). The observed frequency shift is consistent with
      Mie-Gans theory, which indicates electrically active dopant concentrations
      between 10(19) and 10(20) cm(-3). Our findings suggest new opportunities to
      confine light in this ubiquitous semiconductor and engineer the optical
      properties of nontraditional plasmonic materials.

PMID- 22985224
TI  - Compliance mixture modelling with a zero-effect complier class and missing data.
AB  - Randomized experiments are the gold standard for evaluating proposed treatments.
      The intent to treat estimand measures the effect of treatment assignment, but not
      the effect of treatment if subjects take treatments to which they are not
      assigned. The desire to estimate the efficacy of the treatment in this case has
      been the impetus for a substantial literature on compliance over the last 15
      years. In papers dealing with this issue, it is typically assumed there are
      different types of subjects, for example, those who will follow treatment
      assignment (compliers), and those who will always take a particular treatment
      irrespective of treatment assignment. The estimands of primary interest are the
      complier proportion and the complier average treatment effect (CACE). To estimate
      CACE, researchers have used various methods, for example, instrumental variables
      and parametric mixture models, treating compliers as a single class. However, it
      is often unreasonable to believe all compliers will be affected. This article
      therefore treats compliers as a mixture of two types, those belonging to a zero
      effect class, others to an effect class. Second, in most experiments, some
      subjects drop out or simply do not report the value of the outcome variable, and
      the failure to take into account missing data can lead to biased estimates of
      treatment effects. Recent work on compliance in randomized experiments has
      addressed this issue by assuming missing data are missing at random or latently
      ignorable. We extend this work to the case where compliers are a mixture of types
      and also examine alternative types of nonignorable missing data assumptions.

PMID- 22985226
TI  - Molecular diagnostics and the training of future tissue- and cell-based
      pathologists.

PMID- 22985227
TI  - The UEMS section/board of pathology, chapter 6: requirement for recognition of
      postgraduate training in pathology: a presentation of the paris document.
AB  - After more than five years discussion the UEMS Section/Board of Pathology agreed
      a specification of requirements for recognition of post-graduate training in
      pathology, which is the key to the future of our discipline. The document
      published here, subject to ratification by UEMS Council, was voted on and
      accepted by the Pathology Board at the UEMS Paris meeting of 9 June 2012.
      Cytopathology is regarded as integral part of pathology: in general, training in
      pathology takes five years and maintains a common trunk of four (minimum three)
      years where surgical pathology, autopsy pathology and basic knowledge of
      neuropathology, dermatopathology and cytopathology are adequately trained and
      assessed. Training in so-called 'areas of interests' covers the remaining 12-24
      months. Certificates of 'advanced level of competence' remain within the
      authority of national boards. As senior members of its Executive Board, we
      believe that the European Federation of Cytology Societies (EFCS) should take
      responsibility for establishing 1) standards in the quality of cytopathology
      training, 2) training guidelines and qualification for advanced levels of
      competence in cytopathology, 3) manpower planning, 4) tutorials for pathologists
      and cytotechnologists and 4) standards of cytotechnologist training.

PMID- 22985228
TI  - Cytology for pathologists: two sides of the same coin or different views of the
      same side?

PMID- 22985229
TI  - Task-shifting: experiences and opinions of health workers in Mozambique and
      Zambia.
AB  - BACKGROUND: This paper describes the task-shifting taking place in health
      centres and district hospitals in Mozambique and Zambia. The objectives of this
      study were to identify the perceived causes and factors facilitating or impeding
      task-shifting, and to determine both the positive and negative consequences of
      task-shifting for the service users, for the services and for health workers.
      METHODS: Data collection involved individual and group interviews and focus group
      discussions with health workers from the civil service. RESULTS: In both the
      Republic of Mozambique and the Republic of Zambia, health workers have to
      practice beyond the traditional scope of their professional practice to cope with
      their daily tasks. They do so to ensure that their patients receive the level of
      care that they, the health workers, deem due to them, even in the absence of
      written instructions.The "out of professional scope" activities consume a
      significant amount of working time. On occasions, health workers are given on-the
      job training to assume new roles, but job titles and rewards do not change, and
      career progression is unheard of. Ancillary staff and nurses are the two cadres
      assuming a greater diversity of functions as a result of improvised task
      shifting. CONCLUSIONS: Our observations show that the consequences of staff
      deficits and poor conditions of work include heavier workloads for those on duty,
      the closure of some services, the inability to release staff for continuing
      education, loss of quality, conflicts with patients, risks for patients,
      unsatisfied staff (with the exception of ancillary staff) and hazards for health
      workers and managers. Task-shifting is openly acknowledged and widespread,
      informal and carries risks for patients, staff and management.

PMID- 22985231
TI  - Introduction to the special issue on males with eating disorders.

PMID- 22985230
TI  - Role of trehalose in heat and desiccation tolerance in the soil bacterium
      Rhizobium etli.
AB  - BACKGROUND: The compatible solute trehalose is involved in the osmostress
      response of Rhizobium etli, the microsymbiont of Phaseolus vulgaris. In this
      work, we reconstructed trehalose metabolism in R. etli, and investigated its role
      in cellular adaptation and survival to heat and desiccation stress under free
      living conditions. RESULTS: Besides trehalose as major compatible solute, R. etli
      CE3 also accumulated glutamate and, if present in the medium, mannitol. Putative
      genes for trehalose synthesis (otsAB/treS/treZY), uptake (aglEFGK/thuEFGK) and
      degradation (thuAB/treC) were scattered among the chromosome and plasmids p42a,
      p42c, p42e, and p42f, and in some instances found redundant. Two copies of the
      otsA gene, encoding trehalose-6-P-synthase, were located in the chromosome
      (otsAch) and plasmid p42a (otsAa), and the latter seemed to be acquired by
      horizontal transfer. High temperature alone did not influence growth of R. etli,
      but a combination of high temperature and osmotic stress was more deleterious for
      growth than osmotic stress alone. Although high temperature induced some
      trehalose synthesis by R. etli, trehalose biosynthesis was mainly triggered by
      osmotic stress. However, an otsAch mutant, unable to synthesize trehalose in
      minimal medium, showed impaired growth at high temperature, suggesting that
      trehalose plays a role in thermoprotection of R. etli. Desiccation tolerance by
      R. etli wild type cells was dependent of high trehalose production by osmotic pre
      conditioned cells. Cells of the mutant strain otsAch showed ca. 3-fold lower
      survival levels than the wild type strain after drying, and a null viability
      after 4 days storage. CONCLUSIONS: Our findings suggest a beneficial effect of
      osmotic stress in R. etli tolerance to desiccation, and an important role of
      trehalose on the response of R. etli to high temperature and desiccation stress.

PMID- 22985232
TI  - Eating disorders in men: underdiagnosed, undertreated, and misunderstood.
AB  - This article provides a survey of eating disorders in men, highlights the
      dramatic rise in eating disorders, identifies issues specific to males, and
      suggests areas for research and intervention. This survey concludes that men with
      eating disorders are currently under-diagnosed, undertreated, and misunderstood
      by many clinicians who encounter them. Ongoing research addressing these issues
      is expected to result in assessment tools and treatment interventions that will
      advance positive outcomes for men with eating disorders.

PMID- 22985233
TI  - Disordered eating behaviors among Italian men: objectifying media and sexual
      orientation differences.
AB  - Objectification theory was tested as a suitable framework for explaining sexual
      orientation differences in disordered eating behaviors in college-aged Italian
      men. The theory's applicability to 125 homosexual and 130 heterosexual men was
      investigated using self-report questionnaires. Gay men scored significantly
      higher on exposure to sexually objectifying media, body surveillance, body shame,
      disordered eating behaviors, and depression than heterosexual men. Although path
      analyses support the theory's applicability to both groups, for gay men the path
      model demonstrated a better fit to the objectification theory for disordered
      eating and depression. Practical implications are discussed.

PMID- 22985234
TI  - An overview of anorexia nervosa in males.
AB  - This article presents an integrative overview of existing research on anorexia
      nervosa (AN) in adolescent males. AN is commonly thought of as a female disorder.
      Even though as much as 25% of the clinical population is male, research on AN in
      males is limited. Additionally, most conceptualizations of male AN emphasize a
      single etiological factor and, therefore, produce treatments that fail to address
      it as a global phenomenon. In contrast, an integrative understanding that
      incorporates research on the familial, biological, cultural, and psychodynamic
      elements involved in male AN encourages treatment that comprehensively addresses
      the disorder.

PMID- 22985235
TI  - A clinical comparison of men and women on the eating disorder inventory-3 (EDI-3)
      and the eating disorder assessment for men (EDAM).
AB  - This study focused on the most commonly used eating disorder assessment tool, the
      Eating Disorder Inventory-3 (EDI-3), and the preliminary Eating Disorder
      Assessment for Men (EDAM). These assessment tools were examined to investigate
      predictability in males and the extent they differentiated between men and women.
      Specific scales of the EDI-3 and total scores for each instrument were assessed
      using a sample of 108 males and females from residential treatment facilities.
      Overall, the EDI-3 scales were shown to be significantly different between
      genders on a MANOVA, with men scoring significantly lower in body
      dissatisfaction, drive for thinness, and bulimia. Both instruments showed the
      ability to predict eating disorders when using a logistical regression analysis.
      Results support the hypothesis that eating disorders are significantly different
      in men and women, providing evidence that there is a need to develop a valid and
      reliable eating disorder assessment tool specifically for men.

PMID- 22985236
TI  - Eating disorders and pathological gambling in males: can they be differentiated
      by means of weight history and temperament and character traits?
AB  - In the present study, we investigated whether binge/purge eating disorders (ED)
      and pathological gambling (PG) in males can be differentiated by means of weight
      history and temperament and character traits. We investigated 43 male ED
      patients, 46 pathological gamblers and 46 healthy controls (HC) by means of
      lifetime weight information and the Cloninger's Temperament and Character
      Inventory-Revised (TCI-R). The MANCOVA results showed that ED patients showed
      significantly more lifetime weight fluctuations compared with PG and HC after
      controlling for age. Additionally, both ED and PG patients showed significantly
      higher scores on Harm Avoidance and lower Self-Directedness compared with HC.
      Results of a multinomial logistic regression showed that ED versus HC membership
      was determined by more weight fluctuations and lower Self-Directedness; whereas
      ED versus PG membership was determined by more weight fluctuations. Finally, PG
      versus HC membership was characterized by more Harm Avoidance, Novelty Seeking,
      and Persistence, and less Self-directedness. Given that both patient groups were
      characterized by low levels of Self-Directedness (i.e., low levels of effortful
      or executive control), they can benefit from training in self-regulation; and in
      PG patients special attention needs to be given on the training of behavioral
      control in the presence of novel and rewarding stimuli.

PMID- 22985237
TI  - An examination of medical and psychological morbidity in adolescent males with
      eating disorders.
AB  - The objective of this study was to examine the clinical profile of adolescent
      male patients presenting for eating disorder (ED) assessment over a 17-year
      period. A retrospective cohort study was completed. A total of 52 patients (8% of
      the total sample) were included in the study. The average age of patients was
      14.7 years and the most common diagnosis observed was Eating Disorder Not
      Otherwise Specified (EDNOS). Rates of concurrent depression and anxiety were very
      high, as were rates of medical co-morbidity, including osteoporosis. Our study
      supports findings documented in previously published reports of males with eating
      disorders and adds to the limited knowledge base which targets adolescents
      specifically. Multi-center controlled trials are required to further investigate
      male-specific ED symptomatology, treatment courses, and outcomes.

PMID- 22985238
TI  - Are we asking the right questions? A review of assessment of males with eating
      disorders.
AB  - Most of the commonly used eating disorders (ED) assessments were normed and
      developed for females, and their status among male populations is rarely
      addressed in the literature. Recently, some male-specific instruments have been
      developed that may have some utility with this population. This article aims to:
      (a) briefly outline some special considerations and challenges when assessing ED
      in male populations; (b) review the utility of some of the most commonly used ED
      assessments with males; and (c) review some of the measures that have recently
      been developed to assess male-specific ED-related symptoms, with the hope that a
      greater understanding of male-specific presentation may be elucidated.

PMID- 22985239
TI  - Measuring eating disorders in men: development of the eating disorder assessment
      for men (EDAM).
AB  - In a thorough review of literature of eating disorders in men, it is consistently
      shown that symptom presentation varies greatly by gender. However, almost all
      eating disorder instruments have been developed and validated on females. These
      critical differences between men and women in symptom presentation provoke the
      necessity to develop a male specific eating disorder assessment tool. The
      development of the EDAM is described, and in a study of 108 clients of
      residential treatment facilities, results of the preliminary version of the EDAM
      are shown. Internal consistency reliability is supported and factor analysis
      loadings are provided. Results from a logistical regression support the EDAM's
      ability to predict eating disorders in men.

PMID- 22985240
TI  - Norms for the Eating Disorder Examination Questionnaire (EDE-Q) among high school
      and university men.
AB  - This study aimed to establish normative and reliability data for the Eating
      Disorder Examination-Questionnaire (EDE-Q) in a sample of high school and
      university men. A total of 250 men aged 15 to 30 years (mean = 19.7; SD = 2.3)
      with an average BMI of 23.1 (SD = 3.1) were administered the EDE-Q. Mean global
      EDE-Q was 0.44 (SD = 0.52), with subscale means ranging from 0.15 (SD = 0.38) for
      eating concern to 0.70 (SD = 0.81) for shape concern. EDE-Q scores among this non
      clinical sample of normal-weight young men were significantly, and almost
      invariably, lower than similarly aged young women. The EDE-Q performed less
      reliably among men than women, and this is an important caveat. Owing to the
      overall pattern of low item endorsement, reliance upon this single instrument is
      unlikely to provide a comprehensive assessment of shape, weight, and eating
      concerns among normal-weight young men in the community.

PMID- 22985241
TI  - Treatment issues and outcomes for males with eating disorders.
AB  - The aim of this article is to discuss critical issues in treating males with
      eating disorders, and to present assessment and treatment outcome data for 111
      males who received residential treatment for moderate to severe eating disorders.
      Males with eating disorders are often not included in eating disorder research as
      the population of individuals with eating disorders has historically been
      predominantly female. Whether this is due to actual lower prevalence of this
      disorder among males or to fewer males seeking treatment is not clear. In any
      case, there is limited empirical research on the particular treatment issues of
      males, and in treatment environments males are frequently in the minority. We
      have found that an all-male treatment environment is helpful in allowing males to
      benefit from treatment with less stigma. Data are presented which characterize
      psychiatric co-morbidity, excessive exercise, body image, sexuality, and
      spirituality in males. Treatment outcomes for males in this environment are
      positive.

PMID- 22985242
TI  - Male experiences of life after recovery from an eating disorder.
AB  - The aim of this study was to describe how former male patients perceive life
      after recovery from an eating disorder. A qualitative method with a
      phenomenographic approach was used to identify ways of experiencing recovery. Two
      descriptive categories were developed: body acceptance and self-worth. Six
      conceptions describe how recovered patients now relate in a balanced way to
      exercise and food, using strategies to avoid relapse. With a sense of self
      acceptance and autonomy, they now appreciate their social life. Some perceive
      recovery as coping with remaining impulses to diet or exercise. Others experience
      themselves as totally free from the eating disorder.

PMID- 22985244
TI  - The importance of familia for Latina/o college students: examining the role of
      familial support in intragroup marginalization.
AB  - Intragroup marginalization refers to the perceived interpersonal distancing by
      members of the heritage culture when an individual exhibits cultural
      characteristics of the dominant group. This study expands understanding of the
      college experience of Latina/o students by examining relationships between
      intragroup marginalization, college adjustment, resilience, and thriving in a
      sample of 181 Latina/o college students, ranging from freshman to graduate
      students. In addition, the role of familial social support is explored to
      determine any possible mediating effects on the relationship between intragroup
      marginalization, college adjustment, resilience, and thriving. Findings revealed
      that intragroup marginalization predicted college adjustment, resilience, and
      thriving. Familial social support was found to mediate the relationship between
      intragroup marginalization and thriving. This research highlights the negative
      impact of intragroup marginalization for Latina/o students, as well as the role
      of familial support in thriving. The results also shed light on the Latina/o
      college experience as a means to improving Latina/o students' college outcomes.
      (PsycINFO Database Record (c) 2012 APA, all rights reserved).

PMID- 22985245
TI  - "I'm not one of them": barriers to help-seeking among American Indians with
      alcohol dependence.
AB  - The majority of people with alcohol use disorders do not seek formal treatment.
      Research on barriers to help-seeking have only recently focused on ethnic
      minority populations. The present study investigated the extent to which an adult
      American Indian (AI) sample experienced similar and/or unique barriers to help
      seeking as have been reported in the literature. Using both qualitative and
      quantitative methods, 56 (54% male) AIs with lifetime alcohol dependence
      completed a semistructured face-to-face interview and a self-administered written
      survey. Interviews were tape recorded, transcribed, and coded for four major
      themes: personal barriers, pragmatic barriers, concerns about seeking help, and
      social network barriers. Quantitative data provided percentage endorsing each
      survey item and strength of each barrier, which were categorized according to the
      four major themes. In previous research, most barriers questionnaires have not
      queried for cultural concerns or how the specific type of help may be a mismatch
      from the client's perspective. Given the rapidly changing racial/ethnic
      demography in the United States, further research addressing cultural and
      spiritual concerns as well as more common barriers is indicated. (PsycINFO
      Database Record (c) 2012 APA, all rights reserved).

PMID- 22985246
TI  - Diastereoselective additions of titanium enolates from N-glycolyl
      thiazolidinethiones to acetals.
AB  - The stereochemical outcome of the Lewis acid-mediated glycolate addition of the
      titanium enolates from protected N-hydroxyacetyl-4-isopropyl-1,3-thiazolidine-2
      thiones to dimethyl and dibenzyl acetals depends on the hydroxyl protecting
      group. Particularly, the pivaloyl protected glycolate derivative provides the
      reluctant anti adducts in high yields and diastereomeric ratios, which can be
      isolated and further converted in enantiomerically pure form to beta-methoxy or
      beta-benzyloxy alpha-pivaloyloxy carbonyl fragments in a straightforward manner.

PMID- 22985247
TI  - Abscisic acid interacts antagonistically with classical defense pathways in rice
      migratory nematode interaction.
AB  - Studies involving plant-nematode interactions provide an opportunity to unravel
      plant defense signaling in root tissues. In this study, we have characterized the
      roles of salicylate (SA), jasmonate (JA), ethylene (ET) and abscisic acid (ABA)
      in plant defense against the migratory nematode Hirschmanniella oryzae in the
      monocot model plant rice (Oryza sativa). Experiments with exogenous hormone
      applications, biosynthesis inhibition and mutant/transgenic lines were executed
      to test the effect on H. oryzae parasitism in rice roots. Our results demonstrate
      that an intact ET, JA and SA biosynthesis pathway is a prerequisite for defense
      against H. oryzae. By contrast, exogenous ABA treatment drastically compromised
      the rice defense towards this nematode. Gene expression analyses using
      quantitative reverse transcription polymerase chain reaction (qRT-PCR)
      demonstrate that the disease-inducing effect of ABA is likely to be the result of
      an antagonistic interaction between this hormone and the SA/JA/ET-dependent basal
      defense system. Collectively, in rice defense against H. oryzae, at least three
      pathways, namely SA, JA and ET, are important, while ABA plays a negative role in
      defense. Our results suggest that the balance of ABA and SA/JA/ET signaling is an
      important determinant for the outcome of the rice-H. oryzae interaction.

PMID- 22985248
TI  - Occurrence and impact of chronic obstructive pulmonary disease in elderly
      patients with stable heart failure.
AB  - BACKGROUND AND OBJECTIVE: The coexistence of chronic obstructive pulmonary
      disease (COPD) and chronic heart failure (CHF) increases with age. The
      occurrence, prognosis and therapeutic implications of concurrent COPD in elderly
      patients with CHF were investigated. METHODS: One hundred and eighteen
      consecutive patients, >= 65 years old with >= 10 pack/years of smoking and with a
      verified diagnosis of CHF in stable condition, were enrolled. They were followed
      for a mean of 1029 (range 758-1064) days. All patients had spirometry and the
      diagnosis and classification of COPD were made according to Global Initiative for
      Chronic Obstructive Lung Disease guidelines. RESULTS: The mean occurrence of COPD
      was 30% (90% confidence interval: 24-37%). At baseline in patients with CHF and
      COPD, there was a shorter 6-min walk distance, lower arterial oxygen tension,
      glomerular filtration rate and higher N-terminal pro-B-type natriuretic peptide
      (all P < 0.05). The prescription of CHF therapies, including beta-blockers, was
      similar in the two groups. After follow up, the presence of COPD in patients with
      CHF did not appear to influence survival. CONCLUSIONS: COPD is relatively
      frequent in elderly patients with CHF. COPD did not alter survival.

PMID- 22985249
TI  - Atorvastatin preconditioning improves the forward blood flow in the no-reflow
      rats.
AB  - Atorvastatin is not only an antilipemic but also used as an anti-inflammatory
      medicine in heart disease. Our working hypothesis was that atorvastatin
      preconditioning could improve the forward blood flow in the no-reflow rats
      associated with inflammation. We investigated that two doses of atorvastatin
      preconditioning (20 and 5 mg/kg/day) could alleviate deterioration of early
      cardiac diastolic function in rats with inflammation detected by echocardiography
      and haemodynamics. This benefit was obtained from the effect of atorvastatin
      preconditioning on improving forward blood flow and preserving the infarct
      cardiomyocytes, which was estimated by Thioflavin S and TTC staining in rats with
      myocardial ischemia/reperfusion. Subsequently, the improving of forward blood
      flow was ascribed to reduction of microthrombus in microvascular and myocardial
      fibrosis observed by MSB and Masson's trichrome staining with atorvastatin
      preconditioning. Ultimately, we found that atorvastatin preconditioning could
      reduce inflammation factor, such as tumor necrosis factor-alpha and fibrinogen
      like protein 2, both in myocardial and in mononuclear cells, which probably
      attribute to microcirculation dysfunction in no-reflow rats detected by
      immunohistochemistry staining, western blot, and ELISA detection, respectively.
      In conclusion, atorvastatin preconditioning could alleviate deterioration of
      early cardiac diastolic function and improve the forward blood flow in the no
      reflow rats attributing to reduction of TNF-alpha and fgl-2 expression.

PMID- 22985250
TI  - Functional and histological outcome after focal traumatic brain injury is not
      improved in conditional EphA4 knockout mice.
AB  - We investigated the role of the axon guidance molecule EphA4 following traumatic
      brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and
      axonal regeneration following experimental spinal cord injury (SCI). We
      hypothesized that genetic absence of EphA4 could improve functional and
      histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we
      evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or
      sham injury and found it to be downregulated in the hippocampus (p<0.05) but not
      the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the
      behavioral and histological outcome following CCI using WT mice and Emx1-Cre
      driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent
      in the hippocampus and markedly reduced in the cortical regions from embryonic
      day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had
      similar learning and memory abilities at 3 weeks post-TBI compared to WT
      controls, although brain-injured animals performed worse than sham-injured
      controls (p<0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod
      and cylinder tests of motor function up to 29 days post-injury. TBI increased
      cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p<0.05) and
      hippocampal sprouting (Timm stain, p<0.05) and induced a marked loss of
      hemispheric tissue (p<0.05). EphA4 cKO did not alter the histological outcome.
      Although our results may argue against a beneficial role for EphA4 in the
      recovery process following TBI, further studies including post-injury
      pharmacological neutralization of EphA4 are needed to define the role for EphA4
      following TBI.

PMID- 22985251
TI  - Repeatability of a planning target volume expansion protocol for radiation
      therapy of regional lymph nodes in canine and feline patients with head tumors.
AB  - For canine and feline patients with head tumors, simultaneous irradiation of the
      primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often
      indicated. The purpose of this study was to assess the repeatability of a
      planning target volume (PTV) expansion protocol for these LNs. Two CT image sets
      from 44 dogs and 37 cats that underwent radiation therapy for head tumors were
      compared to determine LN repositioning accuracy and precision; planning-CT (for
      radiation therapy planning) and cone-beam CT (at the time of actual treatment
      sessions). Eleven percent of dogs and 65% of cats received treatment to their
      LNs. In dogs, the mandibular LNs were positioned more caudally (P = 0.0002) and
      the right mandibular and right retropharyngeal LNs were positioned more to the
      left side of the patient (P = 0.00015 and P = 0.003, respectively). In cats, left
      mandibular LN was positioned higher (toward roof) than the planning-CT (P =
      0.028). In conclusion, when the patient immobilization devices and bony anatomy
      matching are used to align the primary head target and these LNs are treated
      simultaneously, an asymmetrical PTV expansion that ranges 4-9 mm (dogs) and 2-4
      mm (cats), depending on the directions of couch movement, should be used to
      include the LNs within the PTV at least 95% of the time.

PMID- 22985253
TI  - Identification of human host proteins contributing to H5N1 influenza virus
      propagation by membrane proteomics.
AB  - The highly pathogenic avian influenza (HPAI) H5N1 virus is a highly virulent
      pathogen that causes respiratory diseases and death in humans and other animal
      species worldwide. Because influenza is an enveloped virus, the entry, assembly,
      and budding of virus particles are essential steps in the viral life cycle, and
      the virus relies on the participation of host cellular membrane proteins for all
      of these steps. Thus, we took a comparative membrane proteomics approach by using
      2-DE coupled with MALDI-TOF/TOF MS to profile membrane proteins involved in H5N1
      virus infection at 6, 12, and 24 h. Forty-two different proteins were found to
      vary on A549 cells due to H5N1 virus infection. Of these proteins, 57% were
      membrane or membrane-associated proteins. To further characterize the roles of
      novel identified proteins in virus propagation, the siRNA technology were applied
      and complement component C1q binding protein, annexin 2, prohibitin,
      peroxiredoxin 1 and heat shock protein 90-beta were successfully demonstrated to
      be contributed to viral propagation. In conclusion, the present study provides
      important new insight into understanding the roles of host membrane proteins in
      viral infection progress, and this insight is of particular importance for the
      development of novel therapeutic strategies.

PMID- 22985254
TI  - How to model a negligible probability under the WTO sanitary and phytosanitary
      agreement?
AB  - Since the 1997 EC--Hormones decision, World Trade Organization (WTO) Dispute
      Settlement Panels have wrestled with the question of what constitutes a
      negligible risk under the Sanitary and Phytosanitary Agreement. More recently,
      the 2010 WTO Australia--Apples Panel focused considerable attention on the
      appropriate quantitative model for a negligible probability in a risk assessment.
      The 2006 Australian Import Risk Analysis for Apples from New Zealand translated
      narrative probability statements into quantitative ranges. The uncertainty about
      a "negligible" probability was characterized as a uniform distribution with a
      minimum value of zero and a maximum value of 10(-6) . The Australia - Apples
      Panel found that the use of this distribution would tend to overestimate the
      likelihood of "negligible" events and indicated that a triangular distribution
      with a most probable value of zero and a maximum value of 10-6 would correct the
      bias. The Panel observed that the midpoint of the uniform distribution is 5 * 10
      7 but did not consider that the triangular distribution has an expected value of
      3.3 * 10-7. Therefore, if this triangular distribution is the appropriate
      correction, the magnitude of the bias found by the Panel appears modest. The
      Panel's detailed critique of the Australian risk assessment, and the conclusions
      of the WTO Appellate Body about the materiality of flaws found by the Panel, may
      have important implications for the standard of review for risk assessments under
      the WTO SPS Agreement.

PMID- 22985252
TI  - Metastasis-associated gene, mag-1 improves tumour microenvironmental adaptation
      and potentiates tumour metastasis.
AB  - Metastasis is a major cause of death from malignant diseases, and the underlying
      mechanisms are still largely not known. A detailed probe into the factors which
      may regulate tumour invasion and metastasis contributes to novel anti-metastatic
      therapies. We previously identified a novel metastasis-associated gene 1 (mag-1)
      by means of metastatic phenotype cloning. Then we characterized the gene
      expression profile of mag-1 and showed that it promoted cell migration, adhesion
      and invasion in vitro. Importantly, the disruption of mag-1 via RNA interference
      not only inhibited cellular metastatic behaviours but also significantly reduced
      tumour weight and restrained mouse breast cancer cells to metastasize to lungs in
      spontaneous metastatic assay in vivo. Furthermore, we proved that mag-1
      integrates dual regulating mechanisms through the stabilization of HIF-1alpha and
      the activation of mTOR signalling pathway. We also found that mag-1-induced
      metastatic promotion could be abrogated by mTOR specific inhibitor, rapamycin.
      Taken together, the findings identified a direct role that mag-1 played in
      metastasis and implicated its function in cellular adaptation to tumour
      microenvironment.

PMID- 22985255
TI  - Use of imaging in surveillance of women with early stage breast cancer.
AB  - BACKGROUND: There is no evidence of benefit in terms of survival or quality of
      life for intensive surveillance of women with early breast cancer (BC) and
      current guidelines reflect this. We have examined whether Victorian women, nearly
      4 years from a diagnosis of localized BC, were being managed according to these
      guidelines. METHODS: Participants are women in the BUPA Health Foundation Health
      and Wellbeing after Breast Cancer prospective cohort study. All participants
      completed an enrolment questionnaire within 12 months of diagnosis and then
      completed follow-up questionnaires every 12 months thereafter. In the third
      follow-up questionnaire, completed nearly 4 years from the time of diagnosis,
      women were asked about imaging tests they had in the previous 12 months. RESULTS:
      The analysis was completed on 673 women who were stage 1 at the time of diagnosis
      and had not reported evidence of recurrence or a new BC since diagnosis. Of the
      673, 603 (89.5%) reported having had a mammogram in the previous 12 months and
      319 (52.9% of those having a mammogram) reported a breast ultrasound. Seventy-one
      per cent of women reported no other imaging investigations in the previous 12
      months. CONCLUSIONS: Our study shows that, nearly 4 years from diagnosis,
      Australian practitioners are generally adhering to guidelines about imaging
      surveillance of BC survivors. Practitioners could use the guidelines for the
      education of BC survivors about appropriate health surveillance.

PMID- 22985256
TI  - Preparation of superparamagnetic Fe3O4@alginate/chitosan nanospheres for Candida
      rugosa lipase immobilization and utilization of layer-by-layer assembly to
      enhance the stability of immobilized lipase.
AB  - Superparamagnetic alginate nanospheres with diameter of 50 nm were prepared by
      self-assembly of alginate in the Ca(2+) solution; and then superparamagnetic
      alginate/chitosan nanospheres, which have positive charge and could adsorb lipase
      directly, were obtained with a following assembly of chitosan based on the
      electrostatic interaction between alginate and chitosan. Subsequently, oxidic
      poly (ethylene glycol) was used to functionalize the magnetic alginate/chitosan
      nanospheres. Thus, the magnetic nanospheres with aldehyde groups and a brushlike
      structure were formed. With various characterizations, it was verified that the
      magnetic alginate/chitosan nanospheres held small diameters (around 60 nm) and
      displayed superparamagnetism with high saturation magnetization. The Candida
      rugosa lipase (CRL), meanwhile, was immobilized onto the magnetic
      alginate/chitosan nanospheres by electrostatic adsorption and covalent bonding,
      respectively. Afterward, a layer-by-layer (LBL) assembly process was utilized to
      coat the immobilized CRL (ICRL) with covering layers made up of alginate and
      chitosan. After studying the properties of ICRL such as activity, kinetic
      behaviors, stability and reusability, it was proved that the ICRL prepared with
      two methods displayed more excellent properties than that prepared with
      electrostatic adsorption only. Additionally, coating ICRL with covering layers
      showed good effect on improving the stability of ICRL.

PMID- 22985257
TI  - Eutectic liquid alloys for plasmonics: theory and experiment.
AB  - We report a method based on density functional theory molecular dynamics that
      allows us to calculate the plasmonic properties of liquid metals and metal alloys
      from first principles with no a priori knowledge of the system. We show
      exceptional agreement between the simulated and measured optical constants of
      liquid Ga and the room temperature liquid In-Ga eutectic alloy (T(m) = 289 K). We
      then use this method to analyze the plasmonic properties of various alloy
      concentrations in the In-Ga system. The plasmonic performance of the In-Ga system
      decreases with increasing In concentration. However, the benefits of a room
      temperature plasmonic liquid are likely to outweigh the minor reduction in
      plasmonic performance when moving from pure Ga to the eutectic composition. Our
      results show that density functional theory molecular dynamics can be used as a
      predictive tool for studying the optical properties of liquid metal systems
      amenable to plasmonics.

PMID- 22985258
TI  - Redox brightening of colloidal semiconductor nanocrystals using molecular
      reductants.
AB  - Chemical reductants of sub-conduction-band potentials are demonstrated to induce
      large photoluminescence enhancement in colloidal ZnSe-based nanocrystals. The
      photoluminescence quantum yield of colloidal Mn(2+)-doped ZnSe nanocrystals has
      been improved from 14% to 80% simply by addition of an outer-sphere reductant. Up
      to 48-fold redox brightening is observed for nanocrystals with lower starting
      quantum yields. These increases are quickly reversed upon exposure to air and are
      temporary even under anaerobic conditions. This redox brightening process offers
      a new and systematic approach to understanding redox-active surface "trap states"
      and their contributions to the physical properties of colloidal semiconductor
      nanocrystals.

PMID- 22985259
TI  - Role of peroxynitrite-modified H2A histone in the induction and progression of
      rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease of complex
      aetiology and pathogenesis. In recent years it has become evident that
      apoptotically modified histones exert a central role in the induction of
      autoimmunity, for example in systemic lupus erythematosus (SLE) and RA. Because
      nitric oxide (NO)-related species have been found in inflamed joints of arthritis
      patients, we investigated whether nitrotyrosine is present in sera of RA
      patients, and whether peroxynitrite-modified H2A histone is likely to be involved
      in the induction and progression of RA. METHODS: Commercially available H2A
      histone was modified in vitro by peroxynitrite. The RA patients were divided into
      three groups on the basis of CRP, nitrite, total protein and IgG level. Sera of
      RA patients with high-titre rheumatoid factor (RF) were analysed for
      autoantibodies against native DNA and native and peroxynitrite-modified H2A
      histone. Binding characteristics and specificity of the autoantibodies were
      analysed by direct binding, inhibition enzyme-linked immunosorbent assay (ELISA),
      and band shift assay. RESULTS: Sera from control subjects contained almost
      negligible amounts of 3-nitrotyrosine (3-NT); lower levels were found in group 1
      RA patients in comparison to group 2 and group 3 patients, where the level of
      nitrotyrosine was progressively higher. Enzyme immunoassay data showed
      preferential binding of RA autoantibodies to peroxynitrite-modified H2A histone
      in comparison with native H2A histone or native DNA. The results suggest that
      peroxynitrite modification of self-antigen(s) can generate neoepitopes capable of
      inducing RA characteristic autoantibodies. CONCLUSION: The preferential binding
      of peroxynitrite-modified histones by autoantibodies derived from RA sera
      indicates a role for oxidatively modified and nitrated proteins in the
      initiation/progression of RA.

PMID- 22985260
TI  - Moisture-induced quality changes of hen egg white proteins in a protein/water
      model system.
AB  - In recent years, the intermediate-moisture foods (IMF), such as nutrition and
      energy bars, are a rapidly growing segment of the global food market. However,
      due to moisture-induced protein aggregation, commercial high protein nutrition
      bars generally become harder over time, thus losing product acceptability. In
      this study, the objectives were to investigate the moisture-induced protein
      aggregation in a hen egg white proteins/water dough model system (water activity
      (a(w)): 0.95) and to evaluate its molecular mechanisms and controlling factors.
      During storage at three different temperatures (23, 35, and 45  degrees C) for 70
      days, four selected physicochemical changes of the dough system were analyzed:
      the a(w), the color (L* value), the fluorescent Maillard compounds (fluorescence
      intensity (FI) value), and the remaining free amino groups. Overall, the
      physicochemical changes of egg white proteins in the dough system are closely
      related to the glass transition temperature (T(g)). The effect of moisture
      content on both the L* and FI values occurred as a function of storage time at 45
      degrees C due to the Maillard reaction. The change of the remaining free amino
      groups at different temperatures was derived from the coaction of both the
      Maillard reaction and enzymatic hydrolysis from molds. Additionally, through
      analyzing the buffer-soluble egg white proteins using gel electrophoresis, our
      results showed that moisture-induced aggregates were produced by two chemical
      reactions during storage: the disulfide interaction and the Maillard reaction.
      Furthermore, the effect of two processes during manufacturing, desugarization and
      dry-heat pasteurization, on the physicochemical changes of the egg white proteins
      was elucidated. In order to prevent or reduce moisture-induced protein
      aggregation during product storage and distribution, two potential solutions were
      also discussed.

PMID- 22985261
TI  - Tissue distribution of 2-methoxyestradiol nanosuspension in rats and its
      antitumor activity in C57BL/6 mice bearing lewis lung carcinoma.
AB  - The purpose of the present study was to evaluate the tissue distribution and
      antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension compared with 2-ME
      solution both in vitro and in vivo. 2-ME nanosuspension was made by
      nanoprecipitation-high-frequency ultrasonication method with the particle size of
      168.4 +/- 3.2 nm and the zeta potential of -29.79 +/- 1.89 mV. The overall
      targeting efficiency (TE(Q)) of 2-ME nanosuspension was improved from 28.71 to
      51.95% in the lung of rats. MTT assay showed that 2-ME nanosuspension could
      significantly enhance the in vitro cytotoxicity against lewis lung carcinoma
      (LLC) cells compared with the 2-ME solution, the IC(50) at 72 h was reduced from
      6.35 uM for 2-ME solution to 3.56 uM for 2-ME nanosuspension. The antitumor
      activity in vivo was investigated in C57BL/6 mice bearing LLC, and the results
      indicated that 2-ME nanosuspension not only exhibited significant suppression of
      the tumor growth when compared with that of positive group or cyclophosphamide
      group at the same dose, but also enhanced the spleen indices. Overall, 2-ME
      nanosuspension could mainly deliver the drug to lungs and made the drug
      accumulate in the lungs, so 2-ME nanosuspension has a possible lung cancer
      therapeutic potential.

PMID- 22985262
TI  - Quality of care for major depression and its determinants: a multilevel analysis.
AB  - BACKGROUND: Numerous studies highlight an important gap in the quality of care
      for depression in primary care. However, basic indicators were often used. Few of
      these studies examined factors associated with receiving adequate treatment,
      particularly with a simultaneous consideration of individual and organizational
      characteristics. The purpose of this study was to estimate the proportion of
      primary care patients with a major depressive episode (MDE) who receive adequate
      treatment and to examine the individual and organizational (i.e., clinic-level)
      characteristics associated with the receipt of at least one minimally adequate
      treatment for depression. METHODS: The sample used for this study included 915
      adults consulting a general practitioner (GP), regardless of the motive of
      consultation, meeting DSM-IV criteria for MDE during the 12 months preceding the
      survey (T1), and nested within 65 primary care clinics. Data reported in this
      study were obtained from the "Dialogue" project. Adherence rates for 27 quality
      indicators selected to cover the most important components of depression
      treatment were estimated. Multilevel analyses were conducted. RESULTS: Adherence
      to guidelines was high (>75%) for one third of the quality indicators that were
      measured but was low (<60%) for nearly half of the measures. Just over half of
      the sample (52.2%) received at least one minimally adequate treatment for
      depression. At the individual level, determinants of receipt of minimally
      adequate care included age, having a family physician, a supplementary insurance
      coverage, a comorbid anxiety disorder and the severity of depression. At the
      clinic level, determinants included the availability of psychotherapy on-site,
      the use of treatment algorithms, and the mode of remuneration. CONCLUSIONS: Our
      findings suggest that interventions are needed to increase the extent to which
      primary mental health care conforms to evidence-based recommendations. These
      interventions should target specific populations (i.e. the younger adults and the
      elderly), enhance accessibility to psychotherapy and to a regular family
      physician, and support primary care physicians in their clinical practice with
      patients suffering from depression in different ways such as developing knowledge
      to treat depression and adapting mode of remuneration.

PMID- 22985263
TI  - Production of plasma membrane vesicles with chloride salts and their utility as a
      cell membrane mimetic for biophysical characterization of membrane protein
      interactions.
AB  - Plasma membrane derived vesicles are used as a model system for the biochemical
      and biophysical investigations of membrane proteins and membrane organization.
      The most widely used vesiculation procedure relies on formaldehyde and
      dithiothreitol (DTT), but these active chemicals may introduce artifacts in the
      experimental results. Here we describe a procedure to vesiculate Chinese hamster
      ovary (CHO) cells, widely used for the expression of recombinant proteins, using
      a hypertonic vesiculation buffer containing chloride salts and no formaldehyde or
      DTT. We characterize the size distribution of the produced vesicles. We also show
      that these vesicles can be used for the biophysical characterization of
      interactions between membrane proteins.

PMID- 22985264
TI  - Influence of ozone and radical chemistry on limonene organic aerosol production
      and thermal characteristics.
AB  - Limonene has a strong tendency to form secondary organic aerosol (SOA) in the
      atmosphere and in indoor environments. Initial oxidation occurs mainly via ozone
      or OH radical chemistry. We studied the effect of O(3) concentrations with or
      without a OH radical scavenger (2-butanol) on the SOA mass and thermal
      characteristics using the Gothenburg Flow Reactor for Oxidation Studies at Low
      Temperatures and a volatility tandem differential mobility analyzer. The SOA mass
      using 15 ppb limonene was strongly dependent on O(3) concentrations and the
      presence of a scavenger. The SOA volatility in the presence of a scavenger
      decreased with increasing levels of O(3), whereas without a scavenger, there was
      no significant change. A chemical kinetic model was developed to simulate the
      observations using vapor pressure estimates for compounds that potentially
      contributed to SOA. The model showed that the product distribution was affected
      by changes in both OH and ozone concentrations, which partly explained the
      observed changes in volatility, but was strongly dependent on accurate vapor
      pressure estimation methods. The model-experiment comparison indicated a need to
      consider organic peroxides as important SOA constituents. The experimental
      findings could be explained by secondary condensed-phase ozone chemistry, which
      competes with OH radicals for the oxidation of primary unsaturated products.

PMID- 22985265
TI  - ATR-FTIR and density functional theory study of the structures, energetics, and
      vibrational spectra of phosphate adsorbed onto goethite.
AB  - Periodic plane-wave density functional theory (DFT) and molecular cluster hybrid
      molecular orbital-DFT (MO-DFT) calculations were performed on models of phosphate
      surface complexes on the (100), (010), (001), (101), and (210) surfaces of alpha
      FeOOH (goethite). Binding energies of monodentate and bidentate HPO(4)(2-)
      surface complexes were compared to H(2)PO(4)(-) outer-sphere complexes. Both the
      average potential energies from DFT molecular dynamics (DFT-MD) simulations and
      energy minimizations were used to estimate adsorption energies for each
      configuration. Molecular clusters were extracted from the energy-minimized
      structures of the periodic systems and subjected to energy reminimization and
      frequency analysis with MO-DFT. The modeled P-O and P---Fe distances were
      consistent with EXAFS data for the arsenate oxyanion that is an analog of
      phosphate, and the interatomic distances predicted by the clusters were similar
      to those of the periodic models. Calculated vibrational frequencies from these
      clusters were then correlated with observed infrared bands. Configurations that
      resulted in favorable adsorption energies were also found to produce theoretical
      vibrational frequencies that correlated well with experiment. The relative
      stability of monodentate versus bidentate configurations was a function of the
      goethite surface under consideration. Overall, our results show that phosphate
      adsorption onto goethite occurs as a variety of surface complexes depending on
      the habit of the mineral (i.e., surfaces present) and solution pH. Previous IR
      spectroscopic studies may have been difficult to interpret because the observed
      spectra averaged the structural properties of three or more configurations on any
      given sample with multiple surfaces.

PMID- 22985266
TI  - Two sides of the coin: patient and provider perceptions of health care delivery
      to patients from culturally and linguistically diverse backgrounds.
AB  - BACKGROUND: Australia is a culturally diverse nation with one in seven
      Australians born in a non-English speaking country. Culturally and Linguistically
      Diverse (CALD) populations are at a high risk of developing preventable chronic
      diseases such as cardiovascular disease, type 2 diabetes mellitus, renal disease,
      and chronic respiratory disease, especially communities from the Pacific Islands,
      the Middle East, North Africa, the Indian subcontinent and China. Previous
      studies have shown that access to services may be a contributing factor. This
      study explores the experiences, attitudes and opinions of immigrants from
      different cultural and linguistic backgrounds and their health care providers
      with regard to chronic disease care. METHODS: Five focus groups were conducted
      comprising participants from an Arabic speaking background, or born in Sudan,
      China, Vietnam or Tonga. A total of 50 members participated. All focus groups
      were conducted in the participants' language and facilitated by a trained
      multicultural health worker. In addition, 14 health care providers were
      interviewed by telephone. Interviews were digitally recorded and transcribed. All
      qualitative data were analysed with the assistance of QSR NVivo 8 software.
      RESULTS: Participants were generally positive about the quality and accessibility
      of health services, but the costs of health care and waiting times to receive
      treatment presented significant barriers. They expressed a need for greater
      access to interpreters and culturally appropriate communication and education.
      They mentioned experiencing racism and discriminatory practices. Health
      professionals recommended recruiting health workers from CALD communities to
      assist them to adequately elicit and address the needs of patients from CALD
      backgrounds. CONCLUSIONS: CALD patients, carers and community members as well as
      health professionals all highlighted the need for establishing culturally
      tailored programs for chronic disease prevention and management in CALD
      populations. Better health care can be achieved by ensuring that further
      investment in culturally specific programs and workforce development is in line
      with the number of CALD communities and their needs.

PMID- 22985267
TI  - Theoretical study of structure, stability, and the hydrolysis reactions of small
      iridium oxide nanoclusters.
AB  - The geometric structures and relative stabilities of small iridium oxide
      nanoclusters, Ir(m)O(n) (m = 1-5 and n = 1-2m), have been systematically
      investigated using density functional theory (DFT) calculations at the B3LYP
      level. Our results show that the lowest-energy structures of these clusters can
      be obtained by the sequential oxidation of small "core" iridium clusters. The
      iridium-monoxide-like clusters have relatively higher stability because of their
      relatively high binding energy and second difference in energies. On the basis of
      the optimized lowest-energy structures of neutral and cationic (IrO(2))(n) (n = 1
      5), DFT has been used to study the hydrolysis reaction of these clusters with
      water molecules. The calculated results show that the addition of water molecules
      to the cationic species is much easier than the neutral ones. The overall
      hydrolysis reaction energies are more exothermic for the cationic clusters than
      for the neutral clusters. Our calculations indicate that H(2)O can be more easily
      split on the cationic iridium oxide clusters than on the neutral clusters.

PMID- 22985269
TI  - Cytological and histological findings of thyroid florid papillary hyperplasia.

PMID- 22985270
TI  - Impact of long-term treatment with low-dose inhaled corticosteroids on the bone
      mineral density of chronic obstructive pulmonary disease patients: aggravating or
      beneficial?
AB  - BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is
      characterized by a low-level systemic chronic inflammatory activity that is
      responsible for many of the disease's extra-pulmonary manifestations, including
      osteoporosis and fragility fractures. These manifestations are also well
      documented side-effects of oral corticosteroids. It was hypothesized that low
      levels of inhaled corticosteroids, due to their anti-inflammatory properties and
      their low circulating levels, might preserve the bone mineral density (BMD) of
      COPD patients. METHODS: Two hundred and fifty-one male ex-smokers with COPD
      patients grouped on the basis of their diffusion capacity value as predominantly
      bronchitic or predominantly emphysematic and 313 male controls with similar age
      and smoking history were enrolled in the study. Each of the patient's categories
      was randomized into two separate subgroups. Patients enrolled in subgroups B(neg)
      (n = 91, 36%) and E(neg) (n = 37, 14.7%) were treated with long-acting beta2
      agonists and anticholinergics, while subgroups B(ICS) (n = 87, 35%) and E(ICS) (n
      = 38, 15.1%) were additionally receiving low-dose inhaled corticosteroids.
      Patients and controls were evaluated by clinical examination, lung function
      testing and BMD measurement every 6 months for 4 years. RESULTS: According to the
      findings, emphysematic patients demonstrated an increased rate of BMD loss
      compared with bronchitic patients (P = 0.01). Furthermore, a reduction of the
      annual BMD loss in bronchitic patients on inhaled corticosteroids (P = 0.02) was
      measured, without a corresponding benefit for the emphysematics (P = not
      significant). CONCLUSIONS: Long-term administration of low-dose inhaled
      corticosteroids decelerates the annual BMD loss in bronchitic patients, possibly
      by reducing both pulmonary and systemic chronic inflammation caused by COPD.

PMID- 22985271
TI  - Substituent effect on reactivity of triplet excited state of 2,3
      diazabicyclo[2.2.1]hept-2-enes, DBH derivatives: alpha C-N bond cleavage versus
      beta C-C bond cleavage.
AB  - The photoreaction of a series of 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH)
      derivatives, in which various substituents (X) were introduced at the methano
      bridge carbon of C(7), was investigated under direct (>290 nm) and triplet
      sensitized (Ph2CO, >370 nm) irradiation conditions of the azo chromophore (-Cbeta
      Calpha-N?N-Calpha-Cbeta-). The azo compounds offered a unique opportunity to see
      the substituent X effect at the remote position of the azo chromophore on the
      reactivity of the triplet excited state of bicyclic azoalkanes. The present study
      led to the first observation of the unusual Calpha-Cbeta bond-cleavage reaction
      without the ring stiffness, that is, the structural rigidity, in the triplet
      state of the cyclic azoalkanes. The stereoelectronic effects were found to play
      an important role in lowering the activation energy of the Calpha-Cbeta bond
      cleavage reaction. NBO analyses at the M06-2X/cc-PVDZ level of theory confirmed
      the stereoelectronic effect.

PMID- 22985268
TI  - Clinical isolates of Yersinia enterocolitica biotype 1A represent two
      phylogenetic lineages with differing pathogenicity-related properties.
AB  - BACKGROUND: Y. enterocolitica biotype (BT) 1A strains are often isolated from
      human clinical samples but their contribution to disease has remained a
      controversial topic. Variation and the population structure among the clinical Y.
      enterocolitica BT 1A isolates have been poorly characterized. We used multi-locus
      sequence typing (MLST), 16S rRNA gene sequencing, PCR for ystA and ystB,
      lipopolysaccharide analysis, phage typing, human serum complement killing assay
      and analysis of the symptoms of the patients to characterize 298 clinical Y.
      enterocolitica BT 1A isolates in order to evaluate their relatedness and
      pathogenic potential. RESULTS: A subset of 71 BT 1A strains, selected based on
      their varying LPS patterns, were subjected to detailed genetic analyses. The MLST
      on seven house-keeping genes (adk, argA, aroA, glnA, gyrB, thrA, trpE) conducted
      on 43 of the strains discriminated them into 39 MLST-types. By Bayesian analysis
      of the population structure (BAPS) the strains clustered conclusively into two
      distinct lineages, i.e. Genetic groups 1 and 2. The strains of Genetic group 1
      were more closely related (97% similarity) to the pathogenic bio/serotype 4/O:3
      strains than Genetic group 2 strains (95% similarity). Further comparison of the
      16S rRNA genes of the BT 1A strains indicated that altogether 17 of the 71
      strains belong to Genetic group 2. On the 16S rRNA analysis, these 17 strains
      were only 98% similar to the previously identified subspecies of Y.
      enterocolitica. The strains of Genetic group 2 were uniform in their
      pathogenecity-related properties: they lacked the ystB gene, belonged to the same
      LPS subtype or were of rough type, were all resistant to the five tested
      yersiniophages, were largely resistant to serum complement and did not ferment
      fucose. The 54 strains in Genetic group 1 showed much more variation in these
      properties. The most commonly detected LPS types were similar to the LPS types of
      reference strains with serotypes O:6,30 and O:6,31 (37%), O:7,8 (19%) and O:5
      (15%). CONCLUSIONS: The results of the present study strengthen the assertion
      that strains classified as Y. enterocolitica BT 1A represent more than one
      subspecies. Especially the BT 1A strains in our Genetic group 2 commonly showed
      resistance to human serum complement killing, which may indicate pathogenic
      potential for these strains. However, their virulence mechanisms remain unknown.

PMID- 22985272
TI  - Hindlimb muscle morphology and function in a new atrophy model combining spinal
      cord injury and cast immobilization.
AB  - Contusion spinal cord injury (SCI) animal models are used to study loss of muscle
      function and mass. However, parallels to the human condition typically have been
      confounded by spontaneous recovery observed within the first few post-injury
      weeks, partly because of free cage activity. We implemented a new rat model
      combining SCI with cast immobilization (IMM) to more closely reproduce the
      unloading conditions experienced by SCI patients. Magnetic resonance imaging was
      used to monitor hindlimb muscles' cross-sectional area (CSA) after SCI, IMM
      alone, SCI combined with IMM (SCI+IMM), and in controls (CTR) over a period of 21
      days. Soleus muscle tetanic force was measured in situ on day 21, and hindlimb
      muscles were harvested for histology. IMM alone produced a decrease in triceps
      surae CSA to 63.9+/-4.9% of baseline values within 14 days. In SCI, CSA decreased
      to 75.0+/-10.5% after 7 days, and recovered to 77.9+/-10.7% by day 21. SCI+IMM
      showed the greatest amount of atrophy (56.9+/-9.9% on day 21). In all groups,
      muscle mass and soleus tetanic force decreased in parallel, such that specific
      force was maintained. Extensor digitorum longus (EDL) and soleus fiber size
      decreased in all groups, particularly in SCI+IMM. We observed a significant
      degree of asymmetry in muscle CSA in SCI but not IMM. This effect increased
      between day 7 and 21 in SCI, but also in SCI+IMM, suggesting a minor dependence
      on muscle activity. SCI+IMM offers a clinically relevant model of SCI to
      investigate the mechanistic basis for skeletal muscle adaptations after SCI and
      develop therapeutic approaches.

PMID- 22985273
TI  - Adeno-associated virus serotype 8 gene therapy leads to significant lowering of
      plasma cholesterol levels in humanized mouse models of homozygous and
      heterozygous familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused
      by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a
      bridge to clinical trials, we generated a "humanized" mouse model lacking LDLR
      and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1)
      expression and expressing a human ApoB100 transgene in order to permit more
      authentic simulation of in vivo interactions between the clinical transgene
      product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow
      diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and
      a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than
      in previous mouse models of FH. On injection of an adeno-associated virus
      serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of
      hypercholesterolemia was realized at doses as low as 1.5 * 10(11) genome copies
      (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be
      adequately treated with current therapy, we then extended our studies to
      similarly "humanized" mice that were heterozygous for LDLR deficiency, and that
      have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR
      brought about significant reduction in total and LDL cholesterol at doses as low
      as 5 * 10(11) GC/kg. Collectively, these data demonstrate the safety and efficacy
      of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice
      modeling both hoFH and heFH.

PMID- 22985275
TI  - Abstracts of the 11th International Kidney Cancer Symposium Annual Meeting.
      Chicago, Illinois, USA. October 5-6, 2012.

PMID- 22985274
TI  - Processing pitch in a nonhuman mammal (Chinchilla laniger).
AB  - Whether the mechanisms giving rise to pitch reflect spectral or temporal
      processing has long been debated. Generally, sounds having strong harmonic
      structures in their spectra have strong periodicities in their temporal
      structures. We found that when a wideband harmonic tone complex is passed through
      a noise vocoder, the resulting sound can have a harmonic structure with a large
      peak-to-valley ratio, but with little or no periodicity in the temporal
      structure. To test the role of harmonic structure in pitch perception for a
      nonhuman mammal, we measured behavioral responses to noise-vocoded tone complexes
      in chinchillas (Chinchilla laniger) using a stimulus generalization paradigm.
      Chinchillas discriminated either a harmonic tone complex or an iterated rippled
      noise from a 1-channel vocoded version of the tone complex. When tested with
      vocoded versions generated with 8, 16, 32, 64, and 128 channels, responses were
      similar to those of the 1-channel version. Behavioral responses could not be
      accounted for based on harmonic peak-to-valley ratio as the acoustic cue, but
      could be accounted for based on temporal properties of the autocorrelation
      functions such as periodicity strength or the height of the first peak. The
      results suggest that pitch perception does not arise through spectral processing
      in nonhuman mammals but rather through temporal processing. The conclusion that
      spectral processing contributes little to pitch in nonhuman mammals may reflect
      broader cochlear tuning than that described in humans.

PMID- 22985276
TI  - In this issue. Major changes in health care systems.

PMID- 22985277
TI  - Large-system transformation in health care: a realist review.
AB  - CONTEXT: An evidence base that addresses issues of complexity and context is
      urgently needed for large-system transformation (LST) and health care reform.
      Fundamental conceptual and methodological challenges also must be addressed. The
      Saskatchewan Ministry of Health in Canada requested a six-month synthesis project
      to guide four major policy development and strategy initiatives focused on
      patient- and family-centered care, primary health care renewal, quality
      improvement, and surgical wait lists. The aims of the review were to analyze
      examples of successful and less successful transformation initiatives, to
      synthesize knowledge of the underlying mechanisms, to clarify the role of
      government, and to outline options for evaluation. METHODS: We used realist
      review, whose working assumption is that a particular intervention triggers
      particular mechanisms of change. Mechanisms may be more or less effective in
      producing their intended outcomes, depending on their interaction with various
      contextual factors. We explain the variations in outcome as the interplay between
      context and mechanisms. We nested this analytic approach in a macro framing of
      complex adaptive systems (CAS). FINDINGS: Our rapid realist review identified
      five "simple rules" of LST that were likely to enhance the success of the target
      initiatives: (1) blend designated leadership with distributed leadership; (2)
      establish feedback loops; (3) attend to history; (4) engage physicians; and (5)
      include patients and families. These principles play out differently in different
      contexts affecting human behavior (and thereby contributing to change) through a
      wide range of different mechanisms. CONCLUSIONS: Realist review methodology can
      be applied in combination with a complex system lens on published literature to
      produce a knowledge synthesis that informs a prospective change effort in large
      system transformation. A collaborative process engaging both research producers
      and research users contributes to local applications of universal principles and
      mid-range theories, as well as to a more robust knowledge base for applied
      research. We conclude with suggestions for the future development of synthesis
      and evaluation methods.

PMID- 22985278
TI  - Interpretations of integration in early accountable care organizations.
AB  - CONTEXT: It is widely hoped that accountable care organizations (ACOs) will
      improve health care quality and reduce costs by fostering integration among
      diverse provider groups. But how do implementers actually envision integration,
      and what will integration mean in terms of managing the many social identities
      that ACOs bring together? METHODS: Using the lens of the social identity
      approach, this qualitative study examined how four nascent ACOs engaged with the
      concept of integration. During multiday site visits, we conducted interviews (114
      managers and physicians), observations, and document reviews. FINDINGS: In no
      case was the ACO interpreted as a new, overarching entity uniting disparate
      groups; rather, each site offered a unique interpretation that flowed from its
      existing strategies for social-identity management: An independent practice
      association preserved members' cherished value of autonomy by emphasizing
      coordination, not "integration"; a medical group promoted integration within its
      employed core, but not with affiliates; a hospital, engaging community physicians
      who mistrusted integrated systems, reimagined integration as an equal
      partnership; an integrated delivery system advanced its careful journey towards
      intergroup consensus by presenting the ACO as a cultural, not structural, change.
      CONCLUSIONS: The ACO appears to be a model flexible enough to work in synchrony
      with whatever social strategies are most context appropriate, with the potential
      to promote alignment and functional integration without demanding common
      identification with a superordinate group. "Soft integration" may be a promising
      alternative to the vertically integrated model that, though widely assumed to be
      ideal, has remained unattainable for most organizations.

PMID- 22985279
TI  - Off the hamster wheel? Qualitative evaluation of a payment-linked patient
      centered medical home (PCMH) pilot.
AB  - CONTEXT: Many primary care practices are moving toward the patient-centered
      medical home (PCMH) model and increasingly are offering payment incentives linked
      to PCMH changes. Despite widespread acceptance of general PCMH concepts, there is
      still a pressing need to examine carefully and critically what transformation
      means for primary care practices and their patients and the experience of
      undergoing such change in a practice. METHODS: We used a qualitative case study
      approach to explore the underlying dynamics of change at five practices
      participating in PCMH transformation efforts linked to payment reform. The
      evaluation consisted of structured site visits, interviews, observations, and
      artifact reviews followed by a structured review of transcripts and documents for
      patterns, themes, and insights related to PCMH implementation. FINDINGS: We
      describe both the detailed components of each practice's transformation efforts
      and a grounded taxonomy of eight insights stemming from the experiences of these
      medical homes. We identified specific contextual factors related to wide
      variations in change tactics. We also observed widely varying approaches to
      catalyzing change using (or not) external consultants, specific challenges
      regarding health information technology implementation, team and staff role
      restructuring, compensation, and change fatigue, and several unexpected potential
      confounders or alternative explanations for practice success. CONCLUSIONS: Our
      evaluation affirms the value and necessity of qualitative methods for
      understanding primary care practice transformation, and it should encourage
      ongoing and future pilots to include assessments of the PCMH change process
      beyond clinical markers and claims data. The results raise insights into the
      heterogeneity of medical home transformation, the central but complex role of
      payment reform in creating a space for change, the ability of small practices to
      achieve substantial change in a short time period, and the challenges of
      sustaining it.

PMID- 22985280
TI  - "If we build it, will it stay?" A case study of the sustainability of whole
      system change in London.
AB  - CONTEXT: The long-term sustainability of whole-system change programs is rarely
      studied, and when it is, it is inevitably undertaken in a shifting context,
      thereby raising epistemological and methodological questions. This article
      describes a transferable methodology that was developed to guide the evaluation
      of a three-year follow-up of a large health care change program in London, which
      took place during a period of economic turbulence and rapid policy change.
      METHOD: Using a mixed-method organizational case study design, we studied three
      services (stroke, kidney, and sexual health) across primary and secondary care.
      Each had received L5 million (US$7.8 million) in modernization funding in 2004.
      In 2010/2011, we gathered data on the services and compared them with data from
      2004 to 2008. The new data set contained quantitative statistics (access,
      process, and outcome metrics), qualitative interviews with staff and patients,
      documents, and field notes. Our data analysis was informed by two complementary
      models of sustainability: intervention-focused (guided by the question, What, if
      anything, of the original program has been sustained?) and system-dynamic (guided
      by the question, How and why did change unfold as it did in this complex
      system?). FINDINGS: Some but not all services introduced in the original
      transformation effort of 2004-2008 were still running; others had ceased or been
      altered substantially to accommodate contextual changes (e.g., in case mix,
      commissioning priorities, or national policies). Key cultural changes (e.g.,
      quality improvement, patient centeredness) largely persisted, and innovative
      ideas and practices had spread elsewhere. To draw causal links between the
      original program and current activities and outcomes, it was necessary to weave a
      narrative thread with multiple intervening influences. In particular, against a
      background of continuous change in the local health system, the sustainability of
      the original vision and capacity for quality improvement was strongly influenced
      by (1) stakeholders' conflicting and changing interpretations of the targeted
      health need; (2) changes in how the quality cycle was implemented and monitored;
      and (3) conflicts in stakeholders' values and what each stood to gain or lose.
      CONCLUSIONS: The sustainability of whole-system change embodies a tension between
      the persistence of past practice and the adaptation to a changing context.
      Although the intervention-focused question, What has persisted from the original
      program? (addressed via a conventional logic model), may be appropriate,
      evaluators should qualify their findings by also considering the system-dynamic
      question, What has changed, and why? (addressed by producing a meaningful
      narrative).

PMID- 22985281
TI  - What counts? An ethnographic study of infection data reported to a patient safety
      program.
AB  - CONTEXT: Performance measures are increasingly widely used in health care and
      have an important role in quality. However, field studies of what organizations
      are doing when they collect and report performance measures are rare. An
      opportunity for such a study was presented by a patient safety program requiring
      intensive care units (ICUs) in England to submit monthly data on central venous
      catheter bloodstream infections (CVC-BSIs). METHODS: We conducted an ethnographic
      study involving ~855 hours of observational fieldwork and 93 interviews in 17
      ICUs plus 29 telephone interviews. FINDINGS: Variability was evident within and
      between ICUs in how they applied inclusion and exclusion criteria for the
      program, the data collection systems they established, practices in sending blood
      samples for analysis, microbiological support and laboratory techniques, and
      procedures for collecting and compiling data on possible infections. Those making
      decisions about what to report were not making decisions about the same things,
      nor were they making decisions in the same way. Rather than providing objective
      and clear criteria, the definitions for classifying infections used were seen as
      subjective, messy, and admitting the possibility of unfairness. Reported
      infection rates reflected localized interpretations rather than a standardized
      dataset across all ICUs. Variability arose not because of wily workers
      deliberately concealing, obscuring, or deceiving but because counting was as much
      a social practice as a technical practice. CONCLUSIONS: Rather than objective
      measures of incidence, differences in reported infection rates may reflect, at
      least to some extent, underlying social practices in data collection and
      reporting and variations in clinical practice. The variability we identified was
      largely artless rather than artful: currently dominant assumptions of gaming as
      responses to performance measures do not properly account for how categories and
      classifications operate in the pragmatic conduct of health care. These findings
      have important implications for assumptions about what can be achieved in
      infection reduction and quality improvement strategies.

PMID- 22985282
TI  - Fundamental causes of colorectal cancer mortality: the implications of
      informational diffusion.
AB  - CONTEXT: Colorectal cancer is a major cause of mortality in the United States,
      with 52,857 deaths estimated in 2012. To explore further the social inequalities
      in colorectal cancer mortality, we used fundamental cause theory to consider the
      role of societal diffusion of information and socioeconomic status. METHODS: We
      used the number of deaths from colorectal cancer in U.S. counties between 1968
      and 2008. Through geographical mapping, we examined disparities in colorectal
      cancer mortality as a function of socioeconomic status and the rate of diffusion
      of information. In addition to providing year-specific trends in colorectal
      cancer mortality rates, we analyzed these data using negative binomial
      regression. FINDINGS: The impact of socioeconomic status (SES) on colorectal
      cancer mortality is substantial, and its protective impact increases over time.
      Equally important is the impact of informational diffusion on colorectal cancer
      mortality over time. However, while the impact of SES remains significant when
      concurrently considering the role of diffusion of information, the propensity for
      faster diffusion moderates its effect on colorectal cancer mortality.
      CONCLUSIONS: The faster diffusion of information reduces both colorectal cancer
      mortality and inequalities in colorectal cancer mortality, although it was not
      sufficient to eliminate SES inequalities. These findings have important long-term
      implications for policymakers looking to reduce social inequalities in colorectal
      cancer mortality and other, related, preventable diseases.

PMID- 22985284
TI  - Controlled fabrication of photoactive copper oxide-cobalt oxide nanowire
      heterostructures for efficient phenol photodegradation.
AB  - Fabrication of oxide nanowire heterostructures with controlled morphology,
      interface, and phase purity is critical for high-efficiency and low-cost
      photocatalysis. Here, we have studied the formation of copper oxide-cobalt
      nanowire heterostructures by sputtering and subsequent air annealing to result in
      cobalt oxide (Co(3)O(4))-coated CuO nanowires. This approach allowed fabrication
      of standing nanowire heterostructures with tunable compositions and morphologies.
      The vertically standing CuO nanowires were synthesized in a thermal growth
      method. The shell growth kinetics of Co and Co(3)O(4) on CuO nanowires,
      morphological evolution of the shell, and nanowire self-shadowing effects were
      found to be strongly dependent on sputtering duration, air-annealing conditions,
      and alignment of CuO nanowires. Finite element method (FEM) analysis indicated
      that alignment and stiffness of CuO-Co nanowire heterostructures greatly
      influenced the nanomechanical aspects such as von Mises equivalent stress
      distribution and bending of nanowire heterostructures during the Co deposition
      process. This fundamental knowledge was critical for the morphological control of
      Co and Co(3)O(4) on CuO nanowires with desired interfaces and a uniform coating.
      Band gap energies and phenol photodegradation capability of CuO-Co(3)O(4)
      nanowire heterostructures were studied as a function of Co(3)O(4) morphology.
      Multiple absorption edges and band gap tailings were observed for these
      heterostructures, indicating photoactivity from visible to UV range. A
      polycrystalline Co(3)O(4) shell on CuO nanowires showed the best photodegradation
      performance (efficiency ~50-90%) in a low-powered UV or visible light
      illumination with a sacrificial agent (H(2)O(2)). An anomalously high efficiency
      (~67.5%) observed under visible light without sacrificial agent for CuO nanowires
      coated with thin (~5.6 nm) Co(3)O(4) shell and nanoparticles was especially
      interesting. Such photoactive heterostructures demonstrate unique sacrificial
      agent-free, robust, and efficient photocatalysts promising for organic
      decontamination and environmental remediation.

PMID- 22985285
TI  - Safety management and public spaces: restoring balance.
AB  - Since 2000, the reputation of health and safety in the United Kingdom has been
      tarnished, so much so that it has become the subject of both a media circus and a
      government inquiry. This not only threatens the worthy goals of health and
      safety, but also impacts upon the associated tool of risk assessment itself such
      that "risk assessment" is increasingly seen by the public at large as a term
      inviting ridicule, even abuse. The main thrust of the government's examination of
      health and safety has been its concern that safety requirements were placing a
      disproportionate burden on business. However, there is another source of
      discontent, which is public chagrin over the impact of injury control measures
      upon life beyond the conventional workplace, in particular upon the public spaces
      that people frequent in their leisure time and on the activities they engage in
      there. This article provides a perspective on this second dimension of the crisis
      in confidence. It describes how many U.K. agencies with responsibilities for a
      wide portfolio of public amenities ranging from the provision of play spaces for
      the young to the management of publicly accessible countryside, the maintenance
      of urban and rural trees, the stewardship of sites of cultural heritage, and the
      pursuit of outdoor educational activities have responded to some conflicts posed
      to their services by the new safety culture. It concludes with a discussion of
      implications for the management of public space and for risk assessment itself.

PMID- 22985286
TI  - Diagnostic sensitivity of subjective and quantitative laryngeal ultrasonography
      for recurrent laryngeal neuropathy in horses.
AB  - Recurrent laryngeal neuropathy (RLN) is the most common cause of laryngeal
      hemiplegia in horses and causes neurogenic atrophy of the intrinsic laryngeal
      muscles, including the cricoarytenoideus lateralis muscle. Recurrent laryngeal
      neuropathy results in paresis to paralysis of the vocal fold and arytenoid
      cartilage, which limits performance through respiratory compromise. Ultrasound
      has previously been reported to be a useful diagnostic technique in horses with
      RLN. In this report, the diagnostic sensitivity of subjective and quantitative
      laryngeal ultrasonography was evaluated in 154 horses presented for poor
      performance due to suspected upper airway disease. Ultrasonographic parameters
      recorded were: cricoarytenoideus lateralis echogenicity (subjective and
      quantitative), cricoarytenoideus lateralis thickness, vocal fold movement, and
      arytenoid cartilage movement. Ultrasonographic parameters were then compared with
      laryngeal grades based on resting and exercising upper airway endoscopy.
      Subjectively increased left cricoarytenoideus lateralis echogenicity yielded a
      sensitivity of 94.59% and specificity of 94.54% for detecting RLN, based on the
      reference standard of exercising laryngeal endoscopy. Quantitative left
      cricoarytenoideus lateralis echogenicity values differed among resting laryngeal
      grades I-IV. Findings from this study support previously published findings and
      the utility of subjective and quantitative laryngeal ultrasound as diagnostic
      tools for horses with poor performance.

PMID- 22985287
TI  - The 2009 pandemic H1N1 influenza virus is more pathogenic in pregnant mice than
      seasonal H1N1 influenza virus.
AB  - Pregnant women can experience high mortality, high rates of abortion, and severe
      pneumonia when infected with pandemic influenza viruses. In this context, the
      severity of the 2009 pandemic H1N1 influenza virus compared with seasonal H1N1
      influenza virus is not clear. Presently, in a mouse model of pregnancy, the 2009
      pandemic H1N1 influenza virus killed up to 60% of pregnant mice and caused
      abortion in up to 40%, whereas a circulating seasonal H1N1 influenza virus did
      not cause any deaths or abortions. Higher viral titers and levels of inflammatory
      cytokines and chemokines such as interleukin (IL)-1alpha, IL-6, granulocyte
      colony-stimulating factor, RANTES, monocyte chemotactic protein, and KC (CXCL1),
      were detected in the lungs of pregnant mice infected with the 2009 pandemic H1N1
      influenza virus, compared with the seasonal H1N1 influenza virus. The results of
      our study with pregnant mice suggest that the observed higher pathogenesis in
      pregnant women infected with the 2009 pandemic H1N1 influenza virus than the
      seasonal H1N1 influenza virus may be due to higher viral replication, elevated
      induction of inflammatory chemokines, and reduced progesterone.

PMID- 22985288
TI  - Cytomegalovirus upregulates vascular endothelial growth factor and its second
      cellular kinase domain receptor in human fibroblasts.
AB  - Human cytomegalovirus (HCMV) activation and elevated levels of vascular
      endothelial growth factor (VEGF) have been found to be associated with transplant
      rejection. However, information is lacking about whether elevated levels of this
      multifunctional factor are directly due to viral activation, or if they derive
      from impurities within the culture supernatant of infected cell cultures. We used
      purified as well as unpurified viral stocks to infect human fibroblasts in vitro
      and applied PCR, Western blot, ELISA, and immunofluorescence staining to
      investigate the expression of VEGF and its receptors. Our data suggest that HCMV
      infection triggers an early and sustained induction of VEGF and kinase insert
      domain receptor (KDR) mRNAs, whereas transcript levels of FLT-1 remain unchanged
      by viral infection. Analysis of the extracellular VEGF and cellular KDR protein
      expression after infection with purified and unpurified HCMV strains AD169 and
      TOLEDO showed, in clear contrast to UV-inactivated virus preparations, an
      increased release of VEGF and KDR proteins. In addition, immunofluorescence
      revealed that HCMV infection was also accompanied by a profound increase in
      intracellular VEGF and KDR levels. These results confirm that active HCMV
      infection is required to induce VEGF and the most important VEGF receptor KDR,
      and that the upregulation of VEGF and KDR are a direct viral effect and not a
      secondary effect mediated by inflammatory cytokines within the supernatant. The
      HCMV-dependent upregulation of VEGF and KDR contributes to the theory that viral
      induced immune mediators play a key role in transplant rejection.

PMID- 22985289
TI  - Comparison of the cross-reactive anti-influenza neutralizing activity of
      polymeric and monomeric IgA monoclonal antibodies.
AB  - Here we examined whether polymeric IgA (pIgA) and monomeric IgA (mIgA) antibodies
      differ in their ability to neutralize drift viruses within the same subtype. We
      used an IgA monoclonal antibody (mAb; H1-21) against influenza virus strain
      A/Hiroshima/52/2005 (A/Hiroshima; H3N2). The mAb was obtained after immunizing
      mice mucosally with a split-virion (SV) vaccine. The mAb contained both mIgA and
      pIgA forms. It reacted with the homologous virus and cross-reacted with drift
      viruses A/New York/55/2004 (H3N2) and A/Wyoming/3/2003 (H3N2) in hemagglutinin
      inhibition (HI) and neutralizing Ab assays. The mAb also cross-reacted with
      A/Panama/2007/99 (H3N2) in an ELISA. We separated the mAb into pIgA and mIgA
      fractions by gel filtration, and then tested them for neutralizing Ab activity.
      The neutralizing activity for the A/Hiroshima/52/2005, A/New York/55/2004, and
      A/Wyoming/3/2003 viruses was lower for the mIgA than the pIgA fraction. However,
      the neutralizing efficiency for drift variants relative to that for the homotype
      did not differ between pIgA and mIgA, and pIgA only neutralized variants that
      could also be neutralized by mIgA. These results suggest that the polymerization
      of IgA enhances its antiviral immune responses, but does not increase the number
      of influenza virus strains neutralized by the IgA.

PMID- 22985290
TI  - QconCAT standard for calibration of ion mobility-mass spectrometry systems.
AB  - Ion mobility-mass spectrometry (IM-MS) is a useful technique for determining
      information about analyte ion conformation in addition to mass/charge ratio. The
      physical principles that govern the mobility of an ion through a gas in the
      presence of a uniform electric field are well understood, enabling rotationally
      averaged collision cross sections (Omega) to be directly calculated from measured
      drift times under well-defined experimental conditions. However, such "first
      principle" calculations are not straightforward for Traveling Wave (T-Wave)
      mobility separations due to the range of factors that influence ion motion
      through the mobility cell. If collision cross section information is required
      from T-Wave mobility separations, then calibration of the instruments using known
      standards is essential for each set of experimental conditions. To facilitate
      such calibration, we have designed and generated an artificial protein based on
      the QconCAT technology, QCAL-IM, which upon proteolysis can be used as a
      universal ion mobility calibration standard. This single unique standard enables
      empirical calculation of peptide ion collision cross sections from the drift time
      on a T-Wave mobility instrument.

PMID- 22985291
TI  - Transcriptional reprogramming by root knot and migratory nematode infection in
      rice.
AB  - Rice is one of the most important staple crops worldwide, but its yield is
      compromised by different pathogens, including plant-parasitic nematodes. In this
      study we have characterized specific and general responses of rice (Oryza sativa)
      roots challenged with two endoparasitic nematodes with very different modes of
      action. Local transcriptional changes in rice roots upon root knot (Meloidogyne
      graminicola) and root rot nematode (RRN, Hirschmanniella oryzae) infection were
      studied at two time points (3 and 7 d after infection, dai), using mRNA-seq. Our
      results confirm that root knot nematodes (RKNs), which feed as sedentary
      endoparasites, stimulate metabolic pathways in the root, and enhance nutrient
      transport towards the induced root gall. The migratory RRNs, on the other hand,
      induce programmed cell death and oxidative stress, and obstruct the normal
      metabolic activity of the root. While RRN infection causes up-regulation of
      biotic stress-related genes early in the infection, the sedentary RKNs suppress
      the local defense pathways (e.g. salicylic acid and ethylene pathways).
      Interestingly, hormone pathways mainly involved in plant development were
      strongly induced (gibberellin) or repressed (cytokinin) at 3 dai. These results
      uncover previously unrecognized nematode-induced expression profiles related to
      their specific infection strategy.

PMID- 22985292
TI  - Positive matrix factorization of PM(2.5): comparison and implications of using
      different speciation data sets.
AB  - To evaluate the utility and consistency of different speciation data sets in
      source apportionment of PM(2.5), positive matrix factorization (PMF) coupled with
      a bootstrap technique for uncertainty assessment was applied to four different 1
      year data sets composed of bulk species, bulk species and water-soluble elements
      (WSE), bulk species and organic molecular markers (OMM), and all species. The
      five factors resolved by using only the bulk species best reproduced the observed
      concentrations of PM(2.5) components. Combining WSE with bulk species as PMF
      inputs also produced five factors. Three of them were linked to soil, road dust,
      and processed dust, and together contributed 26.0% of reconstructed PM(2.5) mass.
      A 7-factor PMF solution was identified using speciated OMM and bulk species. The
      EC/sterane and summertime/selective aliphatic factors had the highest
      contributions to EC (39.0%) and OC (53.8%), respectively. The nine factors
      resolved by including all species as input data are consistent with those from
      the previous two solutions (WSE and bulk species, OMM and bulk species) in both
      factor profiles and contributions (r = 0.88-1.00). The comparisons across
      different solutions indicate that the selection of input data set may depend on
      the PM components or sources of interest for specific source-oriented health
      study.

PMID- 22985293
TI  - Sustainable prevention of obesity through integrated strategies: The SPOTLIGHT
      project's conceptual framework and design.
AB  - BACKGROUND: The prevalence of overweight and obesity in Europe is high. It is a
      major cause of the overall rates of many of the main chronic (or non
      communicable) diseases in this region and is characterized by an unequal socio
      economic distribution within the population. Obesity is largely determined by
      modifiable lifestyle behaviours such as low physical activity levels, sedentary
      behaviour and consumption of energy dense diets. It is increasingly being
      recognised that effective responses must go beyond interventions that only focus
      on a specific individual, social or environmental level and instead embrace
      system-based multi-level intervention approaches that address both the individual
      and environment. The EU-funded project "sustainable prevention of obesity through
      integrated strategies" (SPOTLIGHT) aims to increase and combine knowledge on the
      wide range of determinants of obesity in a systematic way, and to identify multi
      level intervention approaches that are strong in terms of Reach, Efficacy,
      Adoption, Implementation and Maintenance (RE-AIM). METHODS/DESIGN: SPOTLIGHT
      comprises a series of systematic reviews on: individual-level predictors of
      success in behaviour change obesity interventions; social and physical
      environmental determinants of obesity; and on the RE-AIM of multi-level
      interventions. An interactive web-atlas of currently running multi-level
      interventions will be developed, and enhancing and impeding factors for
      implementation will be described. At the neighbourhood level, these elements will
      inform the development of methods to assess obesogenicity of diverse
      environments, using remote imaging techniques linked to geographic information
      systems. The validity of these methods will be evaluated using data from surveys
      of health and lifestyles of adults residing in the neighbourhoods surveyed. At
      both the micro- and macro-levels (national and international) the different
      physical, economical, political and socio-cultural elements will be assessed.
      DISCUSSION: SPOTLIGHT offers the potential to develop approaches that combine an
      understanding of the obesogenicity of environments in Europe, and thus how they
      can be improved, with an appreciation of the individual factors that explain why
      people respond differently to such environments. Its findings will inform
      governmental authorities and professionals, academics, NGOs and private sector
      stakeholders engaged in the development and implementation of policies to tackle
      the obesity epidemic in Europe.

PMID- 22985295
TI  - Cervical fascia: a terminological pain in the neck.
AB  - Although understanding the cervical fascia and its arrangement is an important
      part of anatomical, surgical and radiological training, it is inconsistently
      described in textbooks, which makes its study challenging and interdisciplinary
      communication confusing. This review examines the recommended textbooks for
      trainees of these disciplines in order to identify areas of agreement and
      controversy. Not only were the terms used variably between texts, but also key
      aspects of the anatomical descriptions associated with similar terms differed,
      contributing further to the confusion.

PMID- 22985294
TI  - Nanostructured thin film polymer devices for constant-rate protein delivery.
AB  - Herein long-term delivery of proteins from biodegradable thin film devices is
      demonstrated, where a nanostructured polymer membrane controls release. Protein
      was sealed between two poly(caprolactone) films, which generated the thin film
      devices. Protein release for 210 days was shown in vitro, and stable activity was
      established through 70 days with a model protein. These thin film devices present
      a promising delivery platform for biologic therapeutics, particularly for
      application in constrained spaces.

PMID- 22985296
TI  - Popularity and adolescent friendship networks: selection and influence dynamics.
AB  - This study examined the dynamics of popularity in adolescent friendship networks
      across 3 years in middle school. Longitudinal social network modeling was used to
      identify selection and influence in the similarity of popularity among friends.
      It was argued that lower status adolescents strive to enhance their status
      through befriending higher status adolescents, whereas higher status adolescents
      strive to maintain their status by keeping lower status adolescents at a
      distance. The results largely supported these expectations. Selection partially
      accounted for similarity in popularity among friends; adolescents preferred to
      affiliate with similar-status or higher status peers, reinforcing the
      attractiveness of popular adolescents and explaining stability of popularity at
      the individual level. Influence processes also accounted for similarity in
      popularity over time, showing that peers increase in popularity and become more
      similar to their friends. The results showed how selection and influence
      processes account for popularity dynamics in adolescent networks over time.

PMID- 22985297
TI  - Mothers, fathers, and toddlers: parental psychosocial functioning as a context
      for young children's sleep.
AB  - The aim of this study was to investigate the prospective relations between
      parental psychosocial functioning and toddlers' sleep consolidation.
      Investigators met with 85 families 3 times, when children were 15 months (Time 1
      [T1]), 18 months (T2), and 2 years of age (T3). Mothers and fathers completed
      questionnaires pertaining to their parenting stress, marital satisfaction, and
      perceived social support at T1 or T2, and mothers completed child sleep diaries
      at T2 and T3. Results indicated that fathers' parenting stress and marital
      satisfaction, as well as mothers' perceived social support, were related in
      expected directions to children's subsequent sleep consolidation (T3), with or
      without controlling for prior sleep consolidation (T2). In addition, all these
      relations were moderated by family socioeconomic status (SES), such that links
      were stronger in lower SES homes.

PMID- 22985298
TI  - Talking about the near and dear: Infants' comprehension of displaced speech.
AB  - The present research investigated the role of familiarity and proximity in
      infants' comprehension of displaced speech. When 13- and 16-month-old infants
      heard a researcher talk about a familiar person immediately after she left the
      room, they showed comprehension of the name by looking, pointing, or searching
      for the person in question. The majority of 16-month-olds were also able to
      reveal comprehension of the reference to the absent person after a 16-min delay,
      and they were able to respond to the name of an unfamiliar person as well. The 13
      month-olds had more difficulty responding after the delay and to the name of a
      less familiar person. Thus, in the early phases of absent reference
      comprehension, infants' ability to respond to displaced speech can vary as a
      function of the temporal gap between the verbal reference and the last appearance
      of the referent, and of how strong their representation of the referent is.

PMID- 22985299
TI  - Infant reminders alter sympathetic reactivity and reduce couple hostility at the
      transition to parenthood.
AB  - The transition to parenthood marks an important developmental stage in adult
      life, associated with unique challenges to the partners' conflict dialogue in the
      formation of the family unit. Utilizing a biobehavioral experimental design, we
      examined the potential positive effects of the infant on the couple's conflict
      discussion. One hundred forty new parents of 6-month-old infants engaged in a
      face-to-face marital conflict discussion, while sympathetic reactivity was
      recorded online from mother and father and conflict interaction was microcoded
      for hostility and empathy. In the experimental group, a picture of one's own
      infant appeared on a screen halfway into the interaction, whereas controls viewed
      an affectively neutral stimulus. Infant reminders decreased mothers' sympathetic
      arousal, whereas fathers reacted with sympathetic vigilance by preserving
      sympathetic arousal. For both parents, infant reminders decreased couple
      hostility in parent-specific ways. Results accord with life-span developmental
      perspectives, support evolutionary models of mothering and fathering, and suggest
      that infants may enhance the quality of marital dialogue during this stressful
      transition.

PMID- 22985300
TI  - Development of high-performance liquid chromatography-time-of-flight mass
      spectrometry for the simultaneous characterization and quantitative analysis of
      gingerol-related compounds in ginger products.
AB  - Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) was
      established for the simultaneous separation, identification, and quantification
      of gingerol-related compounds in ginger products. The established method has been
      shown to provide a satisfactory linearity (r > 0.999) in a wide range (5-5000
      ng/mL), low limits of detection and quantification, high precision, and inter-
      and intraday repeatability. The detection sensitivity of gingerols and shogaols
      by TOF/MS was 70-100 times higher than conventional UV detection at 288 nm. In
      this study, 19 ginerol-related compounds in the samples were identified and
      quantified by the established LC-TOF/MS method. The dried ginger powder products
      contained the highest quantity of gingerol-related compounds (7126.3-13789.0
      MUg/g), followed by fresh ginger products (2007.9-2790.0 MUg/g), powdered ginger
      tea products (77.29-81.75 MUg/g), and hot water ginger extracts (54.59-123.23
      MUg/mL). Shogaols were not found in fresh gingers. This paper represents the
      first report on the LC-TOF/MS analysis for the simultaneous characterization and
      quantification of gingerol-related compounds in ginger products. 

PMID- 22985301
TI  - Increased blood glycohemoglobin A1c levels lead to overestimation of arterial
      oxygen saturation by pulse oximetry in patients with type 2 diabetes.
AB  - BACKGROUND: Non-enzymatic glycation increases hemoglobin-oxygen affinity and
      reduces oxygen delivery to tissues by altering the structure and function of
      hemoglobin. OBJECTIVES: We investigated whether an elevated blood concentration
      of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter
      oxygen saturation (SpO2) in type 2 diabetic patients during mechanical
      ventilation or oxygen therapy. METHODS: Arterial oxygen saturation (SaO2) and
      partial pressure of oxygen (PO2) were determined with simultaneous monitoring of
      SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation.
      RESULTS: Blood concentration of HbA1c was >7% in 114 patients and <= 7% in 147
      patients. Both SaO2 (96.2 +/- 2.9%, 95% confidence interval [CI] 95.7-96.7% vs.
      95.1 +/- 2.8%, 95% CI 94.7-95.6%) and SpO2 (98.0 +/- 2.6%, 95% CI 97.6-98.5% vs.
      95.3 +/- 2.8%, 95% CI 94.9-95.8%) were significantly higher in patients with
      HbA1c >7% than in those with HbA1c <= 7% (Data are mean +/- SD, all p < 0.01),
      but PO2 did not significantly differ between the two groups. Bland-Altman
      analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 +/-0.55%,
      95% CI 1.73% -1.94%) and limits of agreement (0.76% and 2.92%) in patients with
      HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood
      HbA1c levels (Pearson's r = 0.307, p < 0.01). CONCLUSIONS: Elevated blood HbA1c
      levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood
      gas analysis may be needed for type 2 diabetic patients with poor glycemic
      control during the treatment of hypoxemia.

PMID- 22985302
TI  - Dual-targeting delivery system for bone cancer: synthesis and preliminary
      biological evaluation.
AB  - Chemotherapy in treatment of malignant tumors has many side effects due to the
      poor physiochemical properties and the toxicity to normal tissues. The dual
      targeting drug delivery system combining two high-affinity ligands can target
      anticancer drug primary to the diseased tissue, then to the tumor, which provides
      both greater efficacy of treatment and less harm to normal tissues. In this
      paper, a novel dual-targeting moiety RGD(7) (R-G-D-D-D-D-D-D-D; Nonapeptide for
      bone cancer combining D(6) peptide as bone target moiety and RGD peptide as
      tumors target moiety was contracted. A series of bone and/or tumor targeting
      conjugates have been synthesized in a convergent approach and well characterized
      by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The
      hydroxyapatite (HAP) binding, water solubility, the drug release and the
      distribution in vivo were evaluated. All the conjugates were water-soluble and
      able to release the parent drugs in vitro. The bone-targeting property of the
      dual-targeting delivery system was enhanced from the results of the HAP binding
      and the distribution in vivo. The experiment for verifying tumor targeting
      property was underway. These results provided an effective entry to the
      development of a new dual-targeting delivery system for bone cancer.

PMID- 22985303
TI  - Point and interval estimates of percentile ranks for scores on the Texas
      Functional Living Scale.
AB  - Point and interval estimates of percentile ranks are useful tools in assisting
      with the interpretation of neurocognitive test results. We provide percentile
      ranks for raw subscale scores on the Texas Functional Living Scale (TFLS; Cullum,
      Weiner, & Saine, 2009) using the TFLS standardization sample data (N = 800).
      Percentile ranks with interval estimates are also provided for the overall TFLS T
      score. Conversion tables are provided along with the option of obtaining the
      point and interval estimates using a computer program written to accompany this
      paper (TFLS_PRs.exe). The percentile ranks for the subscales offer an alternative
      to using the cumulative percentage tables in the test manual and provide a useful
      and quick way for neuropsychologists to assimilate information on the case's
      profile of scores on the TFLS subscales. The provision of interval estimates for
      the percentile ranks is in keeping with the contemporary emphasis on the use of
      confidence intervals in psychological statistics.

PMID- 22985304
TI  - Computational study of Xe(OH)4, XeO(OH)3(-), and XeO2(OH)2(2-).
AB  - Because of the vast applicability of noble gases, a more detailed understanding
      of their chemical properties is necessary. Recently, Brock et al. successfully
      synthesized XeO(2) and demonstrated that it has an extended structure in which
      Xe(IV) is oxygen-bridged to four neighboring oxygen atoms using Raman and
      (16/18)O isotopic enrichment studies. On the basis of valence shell electron pair
      repulsion, XeO(2) belongs to the AX(4)E(2) arrangement and assumes a local square
      planar XeO(4) geometry. In contrast, Xe(VIII) assumes a tetrahedral geometry when
      bound to four oxygen atoms. A theoretical comparison of the four-oxygen-bound
      Xe(IV) and Xe(VIII) species, based primarily on the density functional theory
      functional TPSS1KCIS, is presented herein. The properties of XeO(n)(OH)(4-n)(n-)
      species, where n is equal to 0, 1, or 2, were evaluated on this basis, and these
      results are compared with those of the well-known species XeO(4).

PMID- 22985306
TI  - Single-molecule electrochemical gating in ionic liquids.
AB  - The single-molecular conductance of a redox active molecular bridge has been
      studied in an electrochemical single-molecule transistor configuration in a room
      temperature ionic liquid (RTIL). The redox active pyrrolo-tetrathiafulvalene
      (pTTF) moiety was attached to gold contacts at both ends through -(CH(2))(6)S-
      groups, and gating of the redox state was achieved with the electrochemical
      potential. The water-free, room-temperature, ionic liquid environment enabled
      both the monocationic and the previously inaccessible dicationic redox states of
      the pTTF moiety to be studied in the in situ scanning tunneling microscopy (STM)
      molecular break junction configuration. As the electrode potential is swept to
      positive potentials through both redox transitions, an ideal switching behavior
      is observed in which the conductance increases and then decreases as the first
      redox wave is passed, and then increases and decreases again as the second redox
      process is passed. This is described as an "off-on-off-on-off" conductance
      switching behavior. This molecular conductance vs electrochemical potential
      relation could be modeled well as a sequential two-step charge transfer process
      with full or partial vibrational relaxation. Using this view, reorganization
      energies of ~1.2 eV have been estimated for both the first and second redox
      transitions for the pTTF bridge in the 1-butyl-3-methylimidazolium
      trifluoromethanesulfonate (BMIOTf) ionic liquid environment. By contrast, in
      aqueous environments, a much smaller reorganization energy of ~0.4 eV has been
      obtained for the same molecular bridge. These differences are attributed to the
      large, outer-sphere reorganization energy for charge transfer across the
      molecular junction in the RTIL.

PMID- 22985305
TI  - Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine
      and Syrian hamster models of cancer.
AB  - Replication-competent (oncolytic) adenoviruses (OAV) can be adapted as vectors
      for the delivery of therapeutic genes, with the aim of extending the antitumor
      effect beyond direct cytolysis. Transgene expression using these vectors is
      usually intense but short-lived, and repeated administrations are hampered by the
      rapid appearance of neutralizing antibodies (NAbs). We have studied the
      performance of monocytes as cell carriers to improve transgene expression in
      cancer models established in athymic mice and immunocompetent Syrian hamsters.
      Human and hamster monocytic cell lines (MonoMac6 and HM-1, respectively) were
      loaded with replication-competent adenovirus-expressing luciferase. Intravenous
      administration of these cells caused a modest increase in transgene expression in
      tumor xenografts, but this effect was virtually lost in hamsters. In contrast,
      intratumoral administration of HM-1 cells allowed repeated cycles of expression
      and achieved partial protection from NAbs in preimmunized hamsters bearing
      pancreatic tumors. To explore the therapeutic potential of this approach, HM-1
      cells were loaded with a hypoxia-inducible OAV expressing the immunostimulatory
      cytokine interleukin-12 (IL-12). Three cycles of treatment achieved a significant
      antitumor effect in the hamster model, and transgene expression was detected
      following each administration, in contrast with the rapid neutralization of the
      free virus. We propose monocytes as carriers for multiple intratumoral
      administrations of armed OAVs.

PMID- 22985308
TI  - Effect of micro-additions of carbon nanotubes to polymethylmethacrylate on
      reduction in polymerization shrinkage.
AB  - PURPOSE: Carbon nanotubes are used in dentistry, although there are no adequate
      scientific data to support their use in acrylic resins. The polymerization
      shrinkage that occurs with polymethylmethacrylate (PMMA) resins is well known.
      This study compared the polymerization shrinkage of denture base acrylic resin
      with and without micro-additions of carbon nanotubes. MATERIALS AND METHODS: Two
      materials were used, PMMA resin and multiwalled carbon nanotubes. Four groups
      were established of 10 specimens each according to the weight percent of carbon
      nanotubes dispersed and disintegrated in the monomer: group I (0.5% of carbon
      nanotubes in monomer), II (0.25%), III (0.125%), and IV (control group, 0%). The
      polymerization shrinkage of acrylic resin for each group was evaluated based on
      the distance between the reference points in wax (before polymerization) and in
      acrylic (after polymerization), measured using a traveling microscope. The data
      were submitted to Kruskal-Wallis and one-way ANOVA for comparison among the
      groups, and the results were statistically analyzed. RESULTS: The Kruskal-Wallis
      test detected that the different percentages of carbon nanotubes incorporated in
      the monomer showed significant differences, and the mean ranks of polymerization
      shrinkage (%) showed differences among all the groups (group IV = 0.126, III =
      0.037, II = 0.017, I = 0.006). Hence, the order of severity of polymerization
      shrinkage was 0% > 0.125% > 0.25% > 0.5% for the amount of carbon nanotubes
      incorporated in methylmethacrylate. CONCLUSION: The present study was done to
      prove polymerization shrinkage in PMMA resins with micro-additions of carbon
      nanotubes. The results clearly show reduction in polymerization shrinkage when
      carbon nanotubes are incorporated into the PMMA resin.

PMID- 22985307
TI  - Transmitted HIV type 1 drug resistance in newly diagnosed Cuban patients.
AB  - Knowledge of the associated mutations to transmitted drug resistance (TDR) in
      strains of human immunodeficiency virus type 1 (HIV-1) constitutes a fundamental
      premise in epidemiological surveillance. In this present study, TDR from 200
      Cuban patients who were diagnosed with HIV-1 between 2009 and 2011 was analyzed.
      By partial reverse transcriptase polymerase chain reaction (RT-PCR) and
      sequencing of the HIV pol gene, an HIV subtype and transmitted resistance profile
      were determined. The prevalence of associated mutations to the TDR in the
      individuals studied was 21.5%. In the region of the reverse transcriptase, the
      most common mutations were K103N and M184V, while in the region of the protease
      they were L33F and M46L. The results of this study provide evidence of TDR in the
      Cuban seropositive population and suggest the necessity of making resistance
      assays before beginning antiretroviral therapy in HIV-1-infected patients in
      Cuba.

PMID- 22985311
TI  - Zebrafish make it to Hollywood!

PMID- 22985312
TI  - The Barbagli technique: 3-year experience with a modified approach.
AB  - What's known on the subject? and What does the study add? Urethral strictures can
      be treated by various methods, e.g. dilatation and endoscopic treatment, as well
      as with open surgery. However, transurethral treatment shows low long-time
      success rates, while open urethral reconstruction yields good long-term results.
      One of the standard procedures to reconstruct the strictured penile urethra is
      the Barbagli technique, which was introduced in 1996. However, a potential
      drawback of this technique is the suturing of the urethral margins to the second
      side of the graft, because the buccal mucosa is already fixed to the corpus
      cavernosum and the last line is sutured in the back side of the urethra out of
      sight. The present study aims to assess whether the functional results are
      compromised by a modified Barbagli technique, which enables a better
      visualisation of the mucosal margins while making the anastomosis, simplifying
      the original technique. OBJECTIVE: To evaluate stricture recurrence rate as well
      as the satisfaction with the surgery of patients treated with a modified Barbagli
      technique published by our study group in 2009. PATIENTS AND METHODS:
      Retrospective analysis by patient's chart review and unvalidated standardised
      questionnaire of patients treated by the modified Barbagli technique for urethral
      stricture between May 2008 and September 2010. In all, 22 patients were treated
      with the modified Barbagli technique for urethral stricture during this time, and
      18 patients were available for follow-up. Previous surgeries, recurrence rate,
      complications, incontinence, erectile function, satisfaction with the surgery,
      and oral numbness were assessed. As described in the original technique, also in
      the modified technique the access to the urethra is achieved through a midline
      incision. Subsequently, the urethra is completely mobilised. However, it is then
      rotated 180  degrees  using stay sutures. Afterwards, the buccal mucosa is
      sutured into the opened urethra on both sides under vision, giving free access to
      the margins. Once the buccal mucosa is completely sutured in, the urethra is back
      rotated using stay sutures and the margin of the buccal mucosa and the urethra is
      sutured to the tunica albuginea, stretching and supporting the buccal mucosa.
      RESULTS: Follow-up was available for 18 patients with a mean (range) age of 67.5
      (27-74) years. Open previous surgeries had been performed in 27.8% and
      transurethral surgeries in 72.2%. The mean (range) length of the oral mucosa
      graft was 7.8 (2.5-13) cm and the mean operative duration was 106 (73-193) min.
      The success rate was 83.2%; there was no de novo erectile dysfunction and no
      relevant penile curvature. There was oral numbness in two patients (9%). None of
      the recurrence-free patients (83.3%) were dissatisfied with the surgery.
      CONCLUSIONS: The technique simplifies the original technique without compromising
      the functional results. The modification of the technique enables a better
      visualisation of the mucosal margins while making the anastomosis, simplifying
      the original technique. The success rate was comparable with the original
      technique and patient satisfaction with the surgery was high.

PMID- 22985313
TI  - Carbenoid alkene insertion reactions of oxiranyllithiums.
AB  - The first computational investigations of the carbenoid reactions of alpha
      lithiated dimethyl ether (methoxymethyllithium) and the intramolecular and
      intermolecular reactions of lithiated epoxides with the alkene double bond to
      yield cyclopropane rings are presented. These reactions represent the full
      spectrum of known carbenoid pathways to cyclopropanation. The reaction of Li
      CH(2)-O-CH(3) with ethylene proceeds exclusively through a two-step
      carbolithiation pathway, the intramolecular reaction of 1,2-epoxy-5-hexene
      follows either the carbometalation or a concerted methylene transfer pathway (the
      former is energetically more favorable), and the reaction of lithiated ethylene
      oxide (oxiranyllithium) with ethylene, the main focus of this paper, appears to
      proceed exclusively by the methylene transfer mechanism. In the case of these
      latter reactions, the free energy of activation for cyclopropanation tends to
      decrease with the higher aggregation states. Formation of tetramers or higher
      aggregates is favorable in nonpolar solvents, but in strongly coordinating
      solvents such as tetrahydrofuran (THF), steric factors appear to limit aggregate
      sizes to the dimer. In the case of 1,2-epoxy-5-hexene, consideration of competing
      reaction pathways provide an explanation for the observed product distribution.

PMID- 22985309
TI  - An optimized method for delivering flow tracer particles to intravital fluid
      environments in the developing zebrafish.
AB  - Growing evidence suggests that intravital flow-structure interactions are
      critical morphogens for normal embryonic development and disease progression, but
      fluid mechanical studies aimed at investigating these interactions have been
      limited in their ability to visualize and quantify fluid flow. In this study, we
      describe a protocol for injecting small (<=1.0 MUm) tracer particles into fluid
      beds of the larval zebrafish to facilitate microscale fluid mechanical analyses.
      The microinjection apparatus and associated borosilicate pipette design,
      typically blunt-tipped with a 2-4 micron tip O.D., yielded highly linear
      (r(2)=0.99) in vitro bolus ejection volumes. The physical characteristics of the
      tracer particles were optimized for efficient particle delivery. Seeding
      densities suitable for quantitative blood flow mapping (>=50 thousand tracers per
      fish) were routinely achieved and had no adverse effects on zebrafish physiology
      or long-term survivorship. The data and methods reported here will prove valuable
      for a broad range of in vivo imaging technologies [e.g., particle-tracking
      velocimetry, MU-Doppler, digital particle image velocimetry (DPIV), and 4
      dimensional-DPIV] which rely on tracer particles to visualize and quantify fluid
      flow in the developing zebrafish.

PMID- 22985315
TI  - Editorial: Issues in quantitative healthcare research.

PMID- 22985316
TI  - Knowledge creation and the use of secondary data.
AB  - AIMS AND OBJECTIVES: To expose problems of using bespoke questionnaire-based
      surveys to create knowledge and to advance the use of secondary data as an
      alternative research approach. BACKGROUND: Many researchers from students
      undertaking dissertations to those who attempt to create knowledge to advance
      society collect data by using questionnaires. But this raises reliability and
      validity concerns as a consequence of low response rates and non-response bias.
      This constrains knowledge creation. DESIGN AND METHOD: First, the value of
      questionnaire-based research will be discussed. Then, it is argued that much can
      be accomplished using secondary data. The paper concludes by presenting a case
      study developed from the Scottish Health Survey. RESULTS AND CONCLUSION: We
      demonstrate that there may be an alternative for creating bespoke questionnaires
      by researchers. The data to answer their research questions may already exist in
      official surveys whose data are available to students and researchers. By
      analysing a case study, we demonstrate the value of one of these secondary
      sources - the Scottish Health Survey. RELEVANCE TO CLINICAL PRACTICE: We show
      that clinical practitioners in their training and in any professional research
      should consider alternative methods of collecting data for undertaking
      quantitative research. We advance the use of analysis of data collected by
      official surveys. Using secondary data can be more efficient in training students
      in research methods and make dissertations produced more meaningful.

PMID- 22985314
TI  - Rapid characterization of candidate biomarkers for pancreatic cancer using cell
      microarrays (CMAs).
AB  - Tissue microarrays have become a valuable tool for high-throughput analysis using
      immunohistochemical labeling. However, the large majority of biochemical studies
      are carried out in cell lines to further characterize candidate biomarkers or
      therapeutic targets with subsequent studies in animals or using primary tissues.
      Thus, cell line-based microarrays could be a useful screening tool in some
      situations. Here, we constructed a cell microarray (CMA) containing a panel of 40
      pancreatic cancer cell lines available from American Type Culture Collection in
      addition to those locally available at Johns Hopkins. As proof of principle, we
      performed immunocytochemical labeling of an epithelial cell adhesion molecule (Ep
      CAM), a molecule generally expressed in the epithelium, on this pancreatic cancer
      CMA. In addition, selected molecules that have been previously shown to be
      differentially expressed in pancreatic cancer in the literature were validated.
      For example, we observed strong labeling of CA19-9 antigen, a prognostic and
      predictive marker for pancreatic cancer. We also carried out a bioinformatics
      analysis of a literature curated catalog of pancreatic cancer biomarkers
      developed previously by our group and identified two candidate biomarkers, HLA
      class I and transmembrane protease, serine 4 (TMPRSS4), and examined their
      expression in the cell lines represented on the pancreatic cancer CMAs. Our
      results demonstrate the utility of CMAs as a useful resource for rapid screening
      of molecules of interest and suggest that CMAs can become a universal standard
      platform in cancer research.

PMID- 22985317
TI  - Record linkage in Scotland and its applications to health research.
AB  - AIMS AND OBJECTIVES:   This paper will focus on the key concepts behind record
      linkage and describe how probability matching of Scottish health records can be
      used for national health research. BACKGROUND:   Record linkage can bring
      together two or more records relating to the same individual. This allows
      information from multiple sources to be joined together to produce richer data
      sets for research purposes and has wide applicability in public health and
      epidemiological research. The probability matching techniques underpinning record
      linkage bring together records on a patient basis using key identifying
      information on each record. Scotland has a strong track record for performing
      linkage for research purposes owing to routinely collected and well-maintained
      national administrative health data sets, the emergence of the Scottish record
      linkage system and organisations like the Information Services Division of NHS
      National Services Scotland who centrally hold permanently linked patient-based
      databases. Design.  A record linkage retrospective population cohort study is
      described within this paper. METHODS:   The paper will describe current linkage
      methodology before discussing typical applications in the setting of Information
      Services Division and focusing on a particular linkage study investigating rates
      and risk factors for gastroschisis. RESULTS:   Conclusions from the gastroschisis
      study are typical of the types of important findings drawn from analysing linked
      health data. CONCLUSIONS:   Scotland's good track record for linking records for
      health research is evidenced by the high volume of research projects,
      publications and findings resulting from probability matching of national health
      data. Relevance to clinical practice.  Record linkage allows information relating
      to the same person held across different data sources to be brought together.
      Probabilistic record linkage can overcome data quality issues, producing accurate
      matches. This allows linked, analysable, patient-based databases, capable of
      answering complex research questions, to be produced from several data sources
      with wide applications in the field of health research.

PMID- 22985318
TI  - Accuracy of data transfer: double data entry and estimating levels of error.
AB  - AIMS AND OBJECTIVES: Most nursing research using quantitative empirical data
      involves entering information collected on data collection forms into a computer.
      This paper brings to attention issues related to the introduction of errors
      during this transfer of data and makes some recommendations as to how this might
      be dealt with. BACKGROUND: Beyond concerns with the reliability and validity of
      data collection instruments, the issue of data accuracy and the introduction of
      errors in research data sets receive little mention in the nursing research
      literature. Given that studies have reported up to a 26.9 per cent error rate in
      data transfer (Goldberg et al. Proceedings American Medical Informatics
      Association, Annual Symposium November 2008), it is important that this potential
      problem is addressed in the context of nursing research. DESIGN: Discursive
      paper. CONCLUSIONS: An approach to checking the accuracy of data entered onto a
      computer via the keyboard is suggested, and a method for estimating the level of
      confidence that could be claimed regarding the number of errors introduced is
      outlined. RELEVANCE TO CLINICAL PRACTICE: If nursing is to be investigated by
      quantitative methods, it would seem that the accuracy of study findings is
      paramount. This paper identifies one area of research where errors are prone to
      arise and suggests a method for containing these.

PMID- 22985319
TI  - The use of data-mining to identify indicators of health-related quality of life
      in patients with irritable bowel syndrome.
AB  - AIM: To examine the health-related quality of life in a cohort of individuals
      with irritable bowel syndrome and to explore the use of several data-mining
      methods to identify which socio-demographic and irritable bowel syndrome symptoms
      are most highly associated with impaired health-related quality of life.
      BACKGROUND: Health-related quality of life can be adversely affected by irritable
      bowel syndrome. Little is presently known about the predictive factors that may
      influence the quality of life in these patients. DESIGN: Cross-sectional survey
      design involving the general population of the UK. Methods.  Individuals with
      symptoms of irritable bowel syndrome were recruited to a longitudinal cohort
      survey via a UK-wide newspaper advert. Health-related quality of life was
      measured using a battery of validated questionnaires. Several data-mining models
      to determine which factors are associated with impaired health-related quality of
      life are considered in this study and include logistic regression, a
      classification tree and artificial neural networks. RESULTS: As well as irritable
      bowel syndrome symptom severity, results indicate that psychological morbidity
      and socio-demographic factors such as marital status and employment status also
      have a major influence on health-related quality of life in irritable bowel
      syndrome. CONCLUSION: Health-related quality of life is impaired in community
      based individuals in the UK with irritable bowel syndrome. Although not always as
      easily interpreted as logistic regression, data-mining techniques indicate
      subsets of factors that are highly associated with impaired quality of life.
      These models tend to include subsets of irritable bowel syndrome symptoms and
      psychosocial factors. RELEVANCE TO CLINICAL PRACTICE: Identification of the role
      of psychological and socio-demographic factors on health-related quality of life
      may provide more insight into the nature of irritable bowel syndrome. Greater
      understanding of these factors will facilitate more flexible and efficient
      nursing assessment and management of this patient group.

PMID- 22985320
TI  - Editorial: call yourself a nurse? Time to get precious.

PMID- 22985321
TI  - Knowledge of stroke warning signs and risk factors among patients with previous
      stroke or TIA in China.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to describe knowledge about
      stroke warning signs and risk factors in patients with previous stroke or
      transient ischaemic attacks in China and to investigate the relationship between
      socio-demographic characteristics & health status and patients' knowledge about
      stroke. BACKGROUND: Stroke is the leading cause of death and functional
      impairment in China. Survivors are at high risk of new vascular events. Secondary
      prevention after stroke or transient ischaemic attacks is not satisfactory.
      Previous research suggests that awareness of stroke plays an important role in
      facilitating secondary prevention. However, little is known about knowledge of
      stroke warning signs and risk factors among patients with previous
      stroke/transient ischaemic attacks. DESIGN: A cross-sectional questionnaire
      study. METHODS: This study was conducted in Hunan Province, China, between July
      and December in 2010. Subjects were recruited using a cluster sampling method. A
      questionnaire was administered to 1600 patients with stroke/transient ischaemic
      attacks diagnose from eight hospitals, and 1200 patients (75%) responded.
      Patients' knowledge about stroke warning signs and risk factors were collected
      and analysed. Results.  Patients' knowledge about stroke warning signs was very
      poor (only 3.3% identified all warning signs and 28.3% identified three).
      Patients' knowledge about important risk factors (e.g. atrial fibrillation,
      diabetes, metabolic syndrome, etc.) was also very poor (<30%). Patients' action
      in emergency was extremely poor (only 9.2% reported to call emergency service).
      The age, education, stroke-related diagnoses and family history of cardiovascular
      disease were significantly associated with patients' knowledge about stroke.
      CONCLUSIONS: Knowledge about stroke warning signs and risk factors was very poor
      in patients with previous stroke or transient ischaemic attacks in China.
      RELEVANCE TO CLINICAL PRACTICE: Dissemination of stroke knowledge should be a
      core responsibility for Chinese clinical nurse. Future clinical education to
      improve patient's knowledge about stroke and further intervention to manage
      cardiovascular risk factors are indicated.

PMID- 22985322
TI  - The Careful Nursing philosophy and professional practice model.
AB  - AIMS AND OBJECTIVES: To present the Careful Nursing philosophy and professional
      practice model which has its source in the skilled practice of 19th century Irish
      nurses and to propose that its implementation could provide a relevant foundation
      for contemporary nursing practice. BACKGROUND: Nursing models are widely
      considered not relevant to nursing practice. Alarming instances of incompetent
      and insensitive nursing practice and experiences of powerlessness amongst nurses
      are being reported. Professional practice models that will inspire and strengthen
      nurses in practice and help them to address these challenges are needed. Nursing
      history has been suggested as a source of such models. DESIGN: Discursive.
      METHODS: Content analysis of historical documents describing the thinking and
      practice of 19th century Irish nurses. Identification of emergent categories and
      subcategories as philosophical assumptions, concepts and dimensions of
      professional nursing practice. RESULTS: A philosophical approach to practise
      encompassing the nature and innate dignity of the person, the experience of an
      infinite transcendent reality in life processes and health as human flourishing.
      A professional practice model constructed from four concepts; therapeutic milieu,
      practice competence and excellence, management of practice and influence in
      health systems and professional authority; and their eighteen dimensions.
      CONCLUSION: As a philosophy and professional practice model, Careful Nursing can
      engage nurses and provide meaningful direction for practice. It could help
      decrease incidents of incompetent and insensitive practice and sustain already
      exemplary practice. As a basis for theory development, it could help close the
      relevance gap between nursing practice and nursing science. RELEVANCE TO CLINICAL
      PRACTICE: Careful Nursing highlights respect for the innate dignity of all
      persons and what this means for nurses in their relationships with patients. It
      balances attentive tenderness in nurse-patient relationships with clinical skill
      and judgement. It helps nurses to establish their professional practice
      boundaries and take authoritative responsibility for their practice.

PMID- 22985323
TI  - Caregivers' lived experience of assisted feeding.
AB  - AIMS AND OBJECTIVES: The aim of this study was to explore caregivers' experience
      of assisted feeding. BACKGROUND: Assisted feeding presupposes a technical and
      creative coordination of the behaviour of the caregiver and the person who needs
      assistance. To achieve this, the two parties must be able to perceive and
      interpret each other's verbal and non-verbal behaviour and respond. DESIGN: A
      qualitative approach using in-depth semi-structured interviews conducted with
      caregivers was used. METHODS: Twelve caregivers with different educational
      background (nurses and care assistants) were interviewed during 2010.
      Transcriptions of interviews were analysed using the phenomenological guidelines
      by Dahlberg and colleagues. RESULTS: The essence of assisted feeding among
      caregivers was identified to be a healing activity creating a basis for recovery.
      The constituents of the essence were as follows: with simulated calmness, with
      the nutritional aspect in mind, with relatives as source and resource, with work
      experiences and personal preferences as reference points and with inconsistent
      reactions to patient behaviours. CONCLUSION: When performing assisted feeding,
      caregivers adjust their care to the individual patient drawing on their personal
      knowledge and empathy. They mainly focus on the nutritional aspect of assisted
      feeding but also take their own beliefs and societal norms around eating into
      consideration. There seems to be a tension between the importance caregivers
      assign to the nutritional aspect of assisted feeding and the low status this task
      holds, not only in the hierarchy of hospital activities but also among
      caregivers. RELEVANCE TO CLINICAL PRACTICE: An overriding guideline for assisted
      feeding should be formulated, so that the activity will be less dependent on the
      individual caregiver's personal beliefs, time pressure and the character of the
      surroundings.

PMID- 22985324
TI  - Nutrition education and counselling practices in mother and child health clinics:
      study amongst nurses.
AB  - AIMS AND OBJECTIVES: To investigate current nutrition counselling practices,
      knowledge of nutrition and the need for nutrition education by nurses in mother
      and child health clinics. BACKGROUND: Nutrition counselling of young families
      offers a tangible means to implement preventive measures for lifestyle-related
      chronic diseases. Nurses in health clinics are at prime position to execute this
      preventive work, which demands knowledge of current nutrition research as well as
      skill in counselling. Knowledge is limited regarding the current nutrition
      counselling practices of nurses and their needs in improving counselling. DESIGN:
      Descriptive questionnaire survey. METHODS: A questionnaire was formulated and
      sent to nurses in mother and child health clinics (n=650) nationwide via e-mail
      links using a computerised program. Non-respondents were re-contacted twice, the
      final response rate being 50% (n=327). RESULTS: Nurses considered nutrition
      counselling an important but challenging task in the clinics. In addition to
      promotion of health, they had counselled clients in the management of various
      disorders ranging from constipation to coeliac disease. Variability was noted in
      the extent to which nurses had adopted nutrition guidelines. As means to improve
      counselling, better collaboration with both families and healthcare professionals
      and an increase in resources, including time available for counselling, up-to
      date educational material and clinical guidelines, as well as increased education
      in nutrition were suggested. CONCLUSIONS: The results demonstrated a need and a
      readiness amongst nurses to develop nutrition counselling in health clinics.
      Given the health benefits presumably deriving from nutrition counselling,
      investments in operational counselling, comprising advancement of both knowledge
      and skills in the health clinics, are clearly warranted. RELEVANCE TO CLINICAL
      PRACTICES: The findings provide important insights into the current clinical
      practice in health clinics and can be exploited in designing nutrition
      counselling and in-service training.

PMID- 22985325
TI  - Commentary on Brown CE, Ecoff L, Kim SC, Wickline MA, Rose B, Klimpel K and
      Glaser D (2010) Multi-institutional study of barriers to research utilisation and
      evidence-based practice among hospital nurses. Journal of Clinical Nursing 19,
      1944-1951.

PMID- 22985326
TI  - "HealthKick": formative assessment of the health environment in low-resource
      primary schools in the Western Cape Province of South Africa.
AB  - BACKGROUND: This study evaluated the primary school environment in terms of being
      conducive to good nutrition practices, sufficient physical activity and
      prevention of nicotine use, with the view of planning a school-based health
      intervention. METHODS: A sample of 100 urban and rural disadvantaged schools was
      randomly selected from two education districts of the Western Cape Education
      Department, South Africa. A situation analysis, which comprised an interview with
      the school principal and completion of an observation schedule of the school
      environment, was done at all schools. RESULTS: Schools, on average, had 560
      learners and 16 educators. Principals perceived the top health priorities for
      learners to be an unhealthy diet (50%) and to far lesser degree, lack of physical
      activity (24%) and underweight (16%). They cited lack of physical activity (33%)
      and non-communicable diseases (NCDs; 24%) as the main health priorities for
      educators, while substance abuse (66%) and tobacco use (31%) were prioritised for
      parents. Main barriers to health promotion programmes included lack of financial
      resources and too little time in the time table. The most common items sold at
      the school tuck shops were crisps (100%), and then sweets (96%), while vendors
      mainly sold sweets (92%), crisps (89%), and ice lollies (38%). Very few schools
      (8%) had policies governing the type of food items sold at school. Twenty-six of
      the 100 schools that were visited had vegetable gardens. All schools reported
      having physical activity and physical education in their time tables, however,
      not all of them offered this activity outside the class room. Extramural sport
      offered at schools mainly included athletics, netball, and rugby, with cricket
      and soccer being offered less frequently. CONCLUSION: The formative findings of
      this study contribute to the knowledge of key environmental and policy
      determinants that may play a role in the health behaviour of learners, their
      parents and their educators. Evidently, these show that school environments are
      not always conducive to healthy lifestyles. To address the identified
      determinants relating to learners it is necessary to intervene on the various
      levels of influence, i.e. parents, educators, and the support systems for the
      school environment including the curriculum, food available at school, resources
      for physical activity as well as appropriate policies in this regard.

PMID- 22985327
TI  - Potential effects of ongoing and proposed hydropower development on terrestrial
      biological diversity in the Indian Himalaya.
AB  - Indian Himalayan basins are earmarked for widespread dam building, but aggregate
      effects of these dams on terrestrial ecosystems are unknown. We mapped
      distribution of 292 dams (under construction and proposed) and projected effects
      of these dams on terrestrial ecosystems under different scenarios of land-cover
      loss. We analyzed land-cover data of the Himalayan valleys, where dams are
      located. We estimated dam density on fifth- through seventh-order rivers and
      compared these estimates with current global figures. We used a species-area
      relation model (SAR) to predict short- and long-term species extinctions driven
      by deforestation. We used scatter plots and correlation studies to analyze
      distribution patterns of species and dams and to reveal potential overlap between
      species-rich areas and dam sites. We investigated effects of disturbance on
      community structure of undisturbed forests. Nearly 90% of Indian Himalayan
      valleys would be affected by dam building and 27% of these dams would affect
      dense forests. Our model projected that 54,117 ha of forests would be submerged
      and 114,361 ha would be damaged by dam-related activities. A dam density of
      0.3247/1000 km(2) would be nearly 62 times greater than current average global
      figures; the average of 1 dam for every 32 km of river channel would be 1.5 times
      higher than figures reported for U.S. rivers. Our results show that most dams
      would be located in species-rich areas of the Himalaya. The SAR model projected
      that by 2025, deforestation due to dam building would likely result in extinction
      of 22 angiosperm and 7 vertebrate taxa. Disturbance due to dam building would
      likely reduce tree species richness by 35%, tree density by 42%, and tree basal
      cover by 30% in dense forests. These results, combined with relatively weak
      national environmental impact assessment and implementation, point toward
      significant loss of species if all proposed dams in the Indian Himalaya are
      constructed.

PMID- 22985328
TI  - Thin water film formation on metal oxide crystal surfaces.
AB  - Reactions taking place at hydrated metal oxide surfaces are of considerable
      environmental and technological importance. Surface-sensitive X-ray methods can
      provide structural and chemical information on stable interfacial species, but it
      is challenging to perform in situ studies of reaction kinetics in the presence of
      water. We have implemented a new approach to creating a micrometer-scale water
      film on a metal oxide surface by combining liquid and gas jets on a spinning
      crystal. The water films are stable indefinitely and sufficiently thin to allow
      grazing incidence X-ray reflectivity and spectroscopy measurements. The approach
      will enable studies of a wide range of surface reactions and is compatible with
      interfacial optical-pump/X-ray-probe studies.

PMID- 22985329
TI  - Single cell analysis of Vibrio harveyi uncovers functional heterogeneity in
      response to quorum sensing signals.
AB  - BACKGROUND: Vibrio harveyi and closely related species are important pathogens in
      aquaculture. A complex quorum sensing cascade involving three autoinducers
      controls bioluminescence and several genes encoding virulence factors. Single
      cell analysis of a V. harveyi population has already indicated intercellular
      heterogeneity in the production of bioluminescence. This study was undertaken to
      analyze the expression of various autoinducer-dependent genes in individual
      cells. RESULTS: Here we used reporter strains bearing promoter::gfp fusions to
      monitor the induction/repression of three autoinducer-regulated genes in wild
      type conjugates at the single cell level. Two genes involved in pathogenesis -
      vhp and vscP, which code for an exoprotease and a component of the type III
      secretion system, respectively, and luxC (the first gene in the lux operon) were
      chosen for analysis. The lux operon and the exoprotease gene are induced, while
      vscP is repressed at high cell density. As controls luxS and recA, whose
      expression is not dependent on autoinducers, were examined. The responses of the
      promoter::gfp fusions in individual cells from the same culture ranged from no to
      high induction. Importantly, simultaneous analysis of two autoinducer induced
      phenotypes, bioluminescence (light detection) and exoproteolytic activity
      (fluorescence of a promoter::gfp fusion), in single cells provided evidence for
      functional heterogeneity within a V. harveyi population. CONCLUSIONS:
      Autoinducers are not only an indicator for cell density, but play a pivotal role
      in the coordination of physiological activities within the population.

PMID- 22985330
TI  - Inpatient and long-term outcomes of individuals admitted for weaning from
      mechanical ventilation at a specialized ventilation weaning unit.
AB  - BACKGROUND: Weaning from invasive mechanical ventilation (IMV) in specialized
      weaning units has been demonstrated to be safe and cost-effective. Success rates
      and outcomes vary widely, probably relating to patient factors and unit
      expertise. METHODS: An audit was undertaken of patients admitted for weaning from
      IMV at the Austin Hospital Ventilation Weaning Unit (VWU) between March 2002 and
      January 2008. Weaning success, complications and both in-hospital and long-term
      mortality were examined and regression analysis was undertaken to examine factors
      related to these outcomes. RESULTS: Seventy-eight patients were admitted to the
      VWU after a median of 27 days of IMV at their referring centre. Weaning success
      rate (ventilator free or nocturnal non-invasive ventilation only) was 78.2% (n =
      61). Inpatient mortality was 10.2% (n = 8) and serious complications were
      infrequent. Progressive neuromuscular disease (odds ratio 0.10) and sepsis during
      admission to the VWU (odds ratio 0.09) were predictive of weaning failure at
      discharge. Overall survival at 12 months following discharge from the VWU was
      66.7% (n = 52) with most survivors residing in the community. Increasing age
      (hazard ratio 1.93), referral from rural or outer metropolitan centres (hazard
      ratio 3.57 and 2.37 respectively) and a diagnosis of chronic obstructive
      pulmonary disease were associated with increased long-term mortality. CONCLUSION:
      High rates of weaning success with infrequent complications and low mortality
      were achieved in this specialized non-intensive care unit-based weaning unit. The
      VWU may provide a useful template for the development of similar units elsewhere.

PMID- 22985331
TI  - A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors.
AB  - Anaplastic lymphoma kinase (ALK) is an important drug target in many cancers,
      including lymphoma, neuroblastoma, and lung cancer. Here, we demonstrate proof-of
      principle for a novel and inexpensive assay for ALK inhibitor activity and
      identification in zebrafish. We demonstrate that the human oncogenic ALK fusion,
      NPM-ALK, drives overproduction of iridophores, a highly visible, shiny pigment
      cell-type in zebrafish. Treatment with the potent ALK inhibitor, TAE684, fully
      inhibits production of ALK-dependent iridophores. Using our assay, we test
      multiple properties of TAE684 in vivo, including efficacy, specificity, and
      toxicity. We note that TAE684 also inhibits the closely related leukocyte
      tyrosine kinase (Ltk) that is required for endogenous iridophore development.
      Similar effects are observed with an independent inhibitor, Crizotinib. Our assay
      can thus be utilized to identify ALK or LTK inhibitors. Importantly, the natural
      reflectivity of iridophores lends itself to automation for high throughput
      assessment of ALK and LTK inhibitor compounds in vivo.

PMID- 22985332
TI  - Impact of Natural Organic Matter on H2O2-Mediated Oxidation of Fe(II) in Coastal
      Seawaters.
AB  - Whereas the oxidation of inorganic Fe(II) by H(2)O(2) in seawater has been well
      studied, the oxidation of Fe(II) complexes with natural organic matter (NOM) by
      this ubiquitous oxidant has received little attention. Suwannee River fulvic acid
      (SRFA), a proxy for terrestrial NOM, is shown to have a much smaller impact upon
      Fe(II) oxidation kinetics in seawater than the strong effect previously observed
      in freshwater conditions. However, the oxidation kinetics of Fe(II) in seawater
      and freshwater can be quantitatively described employing the same mechanistic
      kinetic model, except that the apparent formation constant of Fe(II)-SRFA
      complexes is substantially decreased under conditions representative of estuarine
      and river-influenced coastal waters. This implies that the same basic processes
      occur in both systems, with differences between Fe(II) oxidation kinetics in
      seawater and freshwater largely attributable to effects of ionic strength and
      matrix composition. This was confirmed with studies employing NaCl solutions with
      or without Mg(2+)/Ca(2+) addition demonstrating that both ionic strength and
      divalent cations effect a decrease in the Fe(II)-binding affinity of SRFA. The
      impact of NOM upon iron redox transformation kinetics is therefore greatly
      influenced by changes in both ionic strength and the presence of cations able to
      compete with Fe(II) for binding sites.

PMID- 22985333
TI  - Folded graphene membranes: mapping curvature at the nanoscale.
AB  - While the unique elastic properties of monolayer graphene have been extensively
      investigated, less knowledge has been developed so far on folded graphene.
      Nevertheless, it has been recently suggested that fold-induced curvature (without
      in-plane strain) could possibly affect the local chemical and electron transport
      properties of graphene, envisaging a material-by-design approach where tailored
      membranes are used in enhanced nanoresonators or nanoelectromechanical devices.
      In this work we propose a novel method combining apparent strain analysis from
      high-resolution transmission electron microscopy (HREM) images and theoretical
      modeling based on continuum elasticity theory and tight-binding atomistic
      simulations to map and measure the nanoscale curvature of graphene folds and
      wrinkles. If enough contrast and resolution in HREM images are obtained, this
      method can be successfully applied to provide a complete nanoscale geometrical
      and physical picture of 3D structure of various wrinkle and fold configurations.

PMID- 22985334
TI  - Pseudogranulomatous Spitz nevus: a variant of Spitz nevus with heavy inflammatory
      infiltrate mimicking a granulomatous dermatitis.
AB  - Spitz nevus is a benign melanocytic proliferation that shows relatively
      characteristic clinicopathologic features. Despite this, Spitz nevus is
      clinically confused with many other lesions, and histopathologically it is
      sometimes difficult to distinguish it from melanoma. However, Spitz nevus rarely
      causes differential diagnostic problems with granulomatous dermatitis. This
      article describes an 8-year-old girl who presented with a nodule on her right
      arm, a clinical appearance of a pyogenic granuloma. Histopathologically, there
      was a dermal lesion composed of aggregates of large epithelioid cells surrounded
      by a heavy inflammatory infiltrate, mimicking a sarcoid-like granulomatous
      dermatitis. Immunohistochemistry showed epithelioid cells with strong nuclear and
      cytoplasmic staining with S-100 protein, thus establishing the diagnosis of a
      melanocytic tumor. The heavy T-cell lymphocytic infiltrate that accompanies the
      large epithelioid cells caused its granulomatous appearance. Molecular assessment
      showed H27H mutation in the HRAS gene. We suggest the term 'pseudogranulomatous'
      for this variant of Spitz nevus because it indicates that the lesion is not
      authentically granulomatous and simply mimics a granulomatous dermatitis. 

PMID- 22985335
TI  - Thyroid cancer in Graves' disease: is surgery the best treatment for Graves'
      disease?
AB  - BACKGROUND: Graves' disease is a common cause of thyrotoxicosis. Treatment
      options include anti-thyroid medications or definitive therapy: thyroidectomy or
      radioactive iodine (I(131) ). Traditionally, I(131) has been the preferred
      definitive treatment for Graves' disease in New Zealand. Reports of concomitant
      thyroid cancer occurring in up to 17% of Graves' patients suggest surgery, if
      performed with low morbidity, may be the preferred option. The aim of this study
      was to determine the rate of thyroid cancer and surgical outcomes in a New
      Zealand cohort of patients undergoing thyroidectomy for Graves' disease. METHOD:
      This study is a retrospective review of Waikato region patients undergoing
      thyroid surgery for Graves' disease during the 10-year period prior to 1 December
      2011. RESULTS: A total of 833 patients underwent thyroid surgery. Of these, 117
      were for Graves' disease. Total thyroidectomy was performed in 82, near-total in
      33 and subtotal in 2 patients. Recurrent thyrotoxicosis developed in one subtotal
      patient requiring I(131) therapy. There were two cases of permanent
      hypoparathyroidism and one of permanent recurrent laryngeal nerve palsy. Eight
      patients (6.8%) had thyroid cancer detected, none of whom had overt nodal
      disease. Five were papillary microcarcinomas (one of which was multifocal), two
      were papillary carcinomas (11 mm and 15 mm) and one was a minimally invasive
      follicular carcinoma. CONCLUSION: Thyroid cancer was identified in approximately
      7% of patients undergoing surgery for Graves' disease. A low complication rate
      (<2%) of permanent hypoparathyroidism and nerve injury (<1%) supports surgery
      being a safe alternative to I(131) especially for patients with young children,
      ophthalmopathy or compressive symptoms.

PMID- 22985336
TI  - Manuka honey-impregnated dressings in the treatment of neuropathic diabetic foot
      ulcers.
AB  - In this study, we investigate the effect of manuka honey-impregnated dressings
      (MHID) on the healing of neuropathic diabetic foot ulcers (NDFU). A total of 63
      Caucasians, type 2 diabetic patients followed up in the diabetic foot outpatient
      clinic comprised the study population. Patients were randomised in two groups as
      follows: group I patients were treated with MHID and group II patients were
      treated with conventional dressings (CD). The patients were followed up on a
      weekly basis for 16 weeks. Mean healing time was 31 +/- 4 days in group I versus
      43 +/- 3 days in group II (P < 0.05). In group I patients 78.13% of ulcers became
      sterile during the first week versus 35.5% in group II patients; the
      corresponding percentages for weeks 2, 4 and 6 were 15.62% versus 38.7%, 6.25%
      versus 12.9% and 0% versus 12.9% respectively. The percent of ulcers healed did
      not differ significantly between groups (97% for MHID and 90% for CD). MHID
      represent an effective treatment for NDFU leading to a significant reduction in
      the time of healing and rapid disinfection of ulcers. 

PMID- 22985337
TI  - Mouse primed embryonic stem cells could be maintained and reprogrammed on human
      amnion epithelial cells.
AB  - Naive and primed embryonic stem cells (ESCs) represent 2 pluripotent states of
      mouse embryonic stem cells (mESCs), corresponding to the pre- and
      postimplantation cells, respectively, in vivo. Primed ESCs are distinct from
      naive cells in biological characteristics, genetic features, developing
      potentials, and antagonistic signal pathway dependences to support
      undifferentiated growth. In vitro, naive mESCs are readily converted to primed
      cells upon transferring to primed pluripotency signaling. ESC-derived epiblast
      stem cells (ESD-EpiSCs) are stabilized primed cells derived from naive mESCs in
      vitro, and cannot be maintained with leukemia inhibitory factor (LIF) signaling
      with or without mouse embryonic fibroblasts as the feeder layer. Here, we show
      that the undifferentiated growth of ESD-EpiSCs could be maintained with the basic
      fibroblast growth factor employing human amnion epithelial cells (hAECs) as the
      feeder layer. Upon exposure to LIF, ESD-EpiSCs could undergo a reprogramming
      process on hAECs and be converted to naive-like cells converted ESCs (cESCs), in
      which naive pluripotency markers were activated, and primed markers were
      suppressed. DNA methylation analysis also validated the epigenetic conversion
      from primed to naive-like pluripotent status. The bone morphogenetic protein 4
      (BMP4) is an important signaling factor in pluripotency controlling, germ cell
      development, and neural commitment. It showed that ESD-EpiSCs and cESCs exhibited
      different features toward BMP4. Our results prove that hAECs are ideal feeder
      cells for both naive and primed ESCs. More importantly, the primed ESCs are
      allowed to be reprogrammed to naive-like pluripotent cells on hAECs. These
      findings suggest that under suitable conditions primed ESCs have the potency of
      converting to naive-like ESCs.

PMID- 22985338
TI  - Phototriggered DNA phosphoramidate ligation in a tandem 5'-amine deprotection/3'
      imidazole activated phosphate coupling reaction.
AB  - We report the preparation and use of an N-methyl picolinium carbamate protecting
      group for applications in a phototriggered nonenzymatic DNA phosphoramidate
      ligation reaction. Selective 5'-amino protection of a modified 13-mer
      oligonucleotide is achieved in aqueous solution by reaction with an N-methyl-4
      picolinium carbonyl imidazole triflate protecting group precursor. Deprotection
      is carried out by photoinduced electron transfer from Ru(bpy)(3)(2+) using
      visible light photolysis and ascorbic acid as a sacrificial electron donor.
      Phototriggered 5'- amino oligonucleotide deprotection is used to initiate a
      nonenzymatic ligation of the 13-mer to an imidazole activated 3'-phospho-hairpin
      template to generate a ligated product with a phosphoramidate linkage. We
      demonstrate that this methodology offers a simple way to exert control over
      reaction initiation and rates in nonenzymatic DNA ligation for potential
      applications in the study of model protocellular systems and prebiotic nucleic
      acid synthesis.

PMID- 22985339
TI  - Context explains divergent effects of anger on risk taking.
AB  - The emotion anger is typically associated with increased risk taking. However,
      anger also produces increased probability estimates that emotionally congruent
      negative events will occur. This latter finding suggests that the general
      assumption that anger always increases risky decision making may be subject to
      caveat. The context of a risk-taking opportunity may dictate whether anger leads
      to greater or lesser acceptance of risk as a function of which component of the
      emotional state (i.e., affective or conceptual) is salient. In the experiment
      reported, participants completed one of two versions of a risk-taking measure
      that differ according to whether they evoke decisions based on affective feelings
      or more deliberate reasoning. Results demonstrated that angry participants made
      riskier decisions than their neutral counterparts under conditions less
      susceptible to the use of affective information, but made less risky decisions
      under conditions that favored the use of affective information. The importance of
      studying emotional states as multifaceted and contextualized phenomenon is
      discussed.

PMID- 22985340
TI  - Moral masochism: on the connection between guilt and self-punishment.
AB  - Do people sometimes seek to atone for their transgressions by harming themselves
      physically? The current results suggest that they do. People who wrote about a
      past guilt-inducing event inflicted more intense electric shocks on themselves
      than did those who wrote about feeling sad or about a neutral event. Moreover,
      the stronger the shocks that guilty participants administered to themselves, the
      more their feelings of guilt were alleviated. We discuss how this method of
      atonement relates to other methods examined in previous research.

PMID- 22985341
TI  - What I see when I think it's about me: people low in rejection-sensitivity
      downplay cues of rejection in self-relevant interpersonal situations.
AB  - Gauging one's impression on a potential mate is challenging. There is a need to
      make reasonably accurate inferences from subtle, dynamic facial expressions and
      to maintain motivation to connect despite the risk of rejection. The
      interpersonal optimism of people low in rejection sensitivity (RS), people who
      confidently expect acceptance rather than anxiously expect rejection, as do their
      high RS counterparts, suggests that they may strategically underestimate social
      threat cues when inferring the impression they have made on others. To test this
      hypothesis, participants viewed the videotaped reactions of individuals said to
      have read the participant's own or someone else's biographical sketch in an
      online dating context, and then estimated the emotions of the targets. Estimates
      of negativity were unrelated to RS when participants believed the videos captured
      the reactions to someone else's biographical sketch. However, to the extent that
      participants were low in RS, they made lower estimates of negativity when they
      believed the videos showed reactions to their biographical sketch compared to
      when they believed the videos captured the reactions to someone else's
      biographical sketch. The tracking accuracy of participants estimating negativity
      was unrelated to RS under either condition, but increased with trait empathy. RS
      was unrelated to estimates of positivity. Supporting functional perspectives on
      interpersonal perception, results show that interpersonal optimism shapes
      impressions of others' reactions to the self in ways that can foster relationship
      initiation.

PMID- 22985342
TI  - Self-relevance appraisal of gaze direction and dynamic facial expressions:
      effects on facial electromyographic and autonomic reactions.
AB  - What processes or mechanisms mediate interpersonal matching of facial expressions
      remains a debated issue. As theoretical approaches to underlying processes (i.e.,
      automatic motor mimicry, communicative intent, and emotional appraisal) make
      different predictions about whether facial responses to others' facial
      expressions are influenced by perceived gaze behavior, we examined the impact of
      gaze direction and dynamic facial expressions on observers' autonomic and rapid
      facial reactions (RFRs). We recorded facial electromyography activity over 4
      muscle regions (Corrugator Supercilli, Zygomaticus Major, Lateral Frontalis, and
      Depressor Anguli Oris), skin conductance response and heart rate changes in
      participants passively exposed to virtual characters displaying approach-oriented
      (anger and happiness), and avoidance-oriented (fear and sadness) emotion
      expressions with gaze either directed at or averted from the observer. Consistent
      with appraisal theories, RFRs were potentiated by mutual eye contact when
      participants viewed happy and angry expressions, while RFRs occurred only to fear
      expressions with averted gaze. RFRs to sad expressions were not affected by gaze
      direction. The interaction between emotional expressions and gaze direction was
      moderated by participants' gender. The pattern of autonomic reactivity was
      consistent with the view that salient social stimuli increase physiological
      arousal and attentional resources, with gaze direction, nature of emotion, and
      gender having moderating effects. These results suggest the critical role of self
      relevance appraisal of senders' contextual perceptual cues and individual
      characteristics to account for interpersonal matching of facial displays.

PMID- 22985343
TI  - Multiprotein heme shuttle pathway in Staphylococcus aureus: iron-regulated
      surface determinant cog-wheel kinetics.
AB  - Iron is a critically important nutrient for all species. Bacteria have evolved
      specialist survival systems to chelate and transport iron across the wall and
      membrane into the cytoplasm. One such system in the human pathogenic bacteria
      Staphylococcus aureus involves extracting heme from hemoglobin and then
      transporting the intact heme across the wall and membrane. The iron-regulated
      surface determinant (Isd) proteins act in concert to carry out the heme
      scavenging and subsequent transport. While details of the static heme-binding
      reaction are currently quite well known, little mechanistic data are available.
      In this paper, we describe detailed time-resolved mass spectral and magnetic
      circular dichroism spectral data recorded as heme is transferred unidirectionally
      from holo-IsdA to apo-IsdE via IsdC. The electrospray mass spectral data
      simultaneously monitor the concentrations of six protein species involved in the
      trans-wall transport of the extracted heme and show for the first time the
      mechanistic details of heme transfer that is key to the Staphylococcus aureus Isd
      heme-scavenging system. Bimolecular kinetic analysis of the ESI-mass spectral
      data shows that heme transfer from IsdA to IsdC is very fast, whereas the
      subsequent heme transfer from IsdC to IsdE is slower. Under limiting IsdC
      conditions, the IsdC intermediary cycles between heme-free and heme-containing
      forms until either all heme has been transferred from holo-IsdA or no further apo
      IsdE is available. The data show that a unique role for IsdC is acting as the
      central cog-wheel that facilitates heme transfer from IsdA to IsdE.

PMID- 22985346
TI  - Electrochemical impedance spectroscopy and atomic force microscopic studies of
      electrical and mechanical properties of nano-black lipid membranes and size
      dependence.
AB  - We present electrochemical impedance spectroscopic (EIS) and two-chamber AFM
      investigations of the electrical and mechanical properties of solvent-containing
      nano-BLMs suspended on chip-based nanopores of diameter of 200, 400, and 700 nm.
      The chips containing nanoporous silicon nitride membranes are fabricated based on
      low-cost colloidal lithography with low aspect ratio of the nanopores. BLMs of
      DPhPC lipid molecules are constructed across the nanopores by the painting
      method. Two equivalent circuits are compared in view of their adequacy in
      description of the EIS performances of the nano-BLMs and more importantly the
      structures associated with the nano-BLMs systems. The BLM resistance and
      capacitance as well as their size and time dependence are studied by EIS. The
      breakthrough forces, elasticity in terms of apparent spring constant, and lateral
      tension of the solvent-containing nano-BLMs are investigated by AFM force
      measurements. The exact relationship of the breakthrough force of the nano-BLM as
      a function of pore size is revealed. Both EIS and AFM studies show increasing
      lifetime and mechanical stability of the nano-BLMs with decreasing pore size.
      Finally, the robust 200 nm diameter nanopores are used to accommodate functional
      BLMs containing DPhPC lipid molecules and gramicidins by using a painting method
      with drop of mixture solutions of DPhPC and gramicidins. EIS investigation of the
      functional nano-BLMs is also performed.

PMID- 22985345
TI  - Vaccine-induced protection against murine schistosomiasis mansoni with larval
      excretory-secretory antigens and papain or type-2 cytokines.
AB  - Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH),
      peroxiredoxin (TPX), and other larval excretory-secretory products (ESP)
      essentially induce T helper (Th) 1 and Th17 immune responses during a non
      protective natural infection. Such an immune environment promotes production of
      nitric oxide and hydrogen peroxide by interferon-gamma-activated monocytes and
      interleukin (IL)-17-mediated recruitment and activation of neutrophils; however,
      it also likely prevents engagement of eosinophils and basophils in the hunt for
      developing larvae. We reasoned that polarizing ESP-induced immune responses
      toward a Th2 phenotype, via the use of cysteine proteases or type-2 cytokines,
      would lead to almost total parasite elimination. Accordingly, outbred mice were
      immunized with 10 MUg recombinant SG3PDH and 15 MUg TPX-derived peptide together
      with 10 MUg papain, or 200 ng thymic stromal lymphopoietin, IL-25, or IL-33 as an
      adjuvant. Two weeks later, untreated mice, adjuvant controls, and immunized mice
      were challenged with 100 or 125 cercariae. Results of 6 experiments indicated
      that these formulations elicited IgM, IgG1, and IgA specific antibodies, and an
      increase in ex vivo spleen cells release of IL-4 and IL-5 correlated with highly
      significant (up to P < 0.0001) reduction of 62 to 78% in challenge worm burden.
      Improvement of ESP selection, singly or in a combination, and immunization
      regimen, namely ESP and type-2 cytokine dose and injection site and schedule,
      could lead to a sterilizing schistosomiasis vaccine in the foreseeable future.

PMID- 22985344
TI  - Management of imported malaria in Europe.
AB  - In this position paper, the European Society for Clinical Microbiology and
      Infectious Diseases, Study Group on Clinical Parasitology, summarizes main issues
      regarding the management of imported malaria cases. Malaria is a rare diagnosis
      in Europe, but it is a medical emergency. A travel history is the key to
      suspecting malaria and is mandatory in patients with fever. There are no specific
      clinical signs or symptoms of malaria although fever is seen in almost all non
      immune patients. Migrants from malaria endemic areas may have few
      symptoms.Malaria diagnostics should be performed immediately on suspicion of
      malaria and the gold- standard is microscopy of Giemsa-stained thick and thin
      blood films. A Rapid Diagnostic Test (RDT) may be used as an initial screening
      tool, but does not replace urgent microscopy which should be done in parallel.
      Delays in microscopy, however, should not lead to delayed initiation of
      appropriate treatment. Patients diagnosed with malaria should usually be
      hospitalized. If outpatient management is preferred, as is the practice in some
      European centres, patients must usually be followed closely (at least daily)
      until clinical and parasitological cure. Treatment of uncomplicated Plasmodium
      falciparum malaria is either with oral artemisinin combination therapy (ACT) or
      with the combination atovaquone/proguanil. Two forms of ACT are available in
      Europe: artemether/lumefantrine and dihydroartemisinin/piperaquine. ACT is also
      effective against Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and
      Plasmodium knowlesi, but these species can be treated with chloroquine. Treatment
      of persistent liver forms in P. vivax and P. ovale with primaquine is indicated
      after excluding glucose 6 phosphate dehydrogenase deficiency. There are modified
      schedules and drug options for the treatment of malaria in special patient
      groups, such as children and pregnant women. The potential for drug interactions
      and the role of food in the absorption of anti-malarials are important
      considerations in the choice of treatment.Complicated malaria is treated with
      intravenous artesunate resulting in a much more rapid decrease in parasite
      density compared to quinine. Patients treated with intravenous artesunate should
      be closely monitored for haemolysis for four weeks after treatment. There is a
      concern in some countries about the lack of artesunate produced according to Good
      Manufacturing Practice (GMP).

PMID- 22985347
TI  - Updates from the Sixth International Congress 'Psoriasis: from Gene to Clinic',
      the Queen Elizabeth II Conference Centre, London, U.K., 1-3 December 2011.
AB  - The 15 years between the First International Congress 'Psoriasis: from Gene to
      Clinic' and the Sixth Congress held in London from 1 to 3 December 2011 have seen
      extraordinary progress in the sciences that are relevant to psoriasis and
      therapeutics that have transformed its treatment. Over this time, 'Psoriasis:
      from Gene to Clinic' has emerged as the premier conference for clinicians and
      scientists interested in this field. Its popularity is attested to by the 450
      registered delegates from the U.K. and around the world, which necessitated a
      change of venue to the excellent facilities of the Queen Elizabeth II Conference
      Centre. Although the content has evolved over the years, the structure of this 3
      day conference has remained similar. The first day was given to genetics,
      comorbidities and outcome measures. Immunology and immunity were covered on the
      second day and therapeutics on the third. The stature of the three keynote
      lecturers and eight invited speakers was truly world class and their
      presentations were interspersed with 23 free communications. Here we review
      highly selected personal highlights of the meeting that we hope will be of
      general interest.

PMID- 22985348
TI  - Uncertainty and perception of danger among patients undergoing treatment for
      prostate cancer.
AB  - Study Type - Therapy (attitude prevalence) Level of Evidence 2a What's known on
      the subject? and What does the study add? Marked differences in uncertainty among
      patients have been found relating to race and social environment indicating that
      as uncertainty increases, social functioning declines. Correlations have been
      found between uncertainty and patients' coping, psychological adjustment and
      perceptions of their health and illness. Studies suggest the detrimental effect
      of uncertainty among patients with prostate cancer in the perception of their
      quality of life. These studies underline the potential benefit of targeted
      intervention. The study provides a unique insight into the impact of uncertainty
      and perception of danger on overall satisfaction with treatment outcomes in men
      with prostate cancer. Its results suggest that possible disparities related to
      patient racial background and education may exist in the perception of cancer
      related uncertainty. Racial and educational disparities, coupled with a mild to
      moderate association of uncertainty or danger perception and overall outcome
      satisfaction, suggest an unmet need for healthcare and nursing services for men
      undergoing treatment for prostate cancer. OBJECTIVES: To investigate patient
      uncertainty and perception of danger regarding prospects for clinical prostate
      cancer control. To determine the impact of these factors on satisfaction with
      overall prostate cancer treatment outcome. PATIENTS AND METHODS: Men who had
      undergone primary treatment for early stage prostate cancer and who were
      participants in the Prostate Cancer Outcomes and Satisfaction with Treatment
      Quality Assessment (PROSTQA) prospective cohort study of prostate cancer outcomes
      (the parent study) were offered the opportunity to participate in the present
      study. Centralized phone interviews were conducted to determine patient-reported
      uncertainty regarding cancer status (measured by the Mishel Uncertainty in
      Illness Scale-Community Form), perception of danger (measured by Folkman and
      Lazarus' Appraisal Scale) and satisfaction with treatment outcome (measured by
      the Service Satisfaction Scale for Cancer Care). The study used the same
      centralized telephone interview centre as was used in the parent study. Data were
      collected at 48, 60 or 72 months after the completion of prostate cancer
      treatment. Relationships among measures were characterized by Spearman rank
      correlation coefficients (r). RESULTS: A total of 338 agreed to participate,
      representing 76% of those who were invited. Younger patients experienced less
      uncertainty (r = 0.20, P < 0.001), yet reported greater perception of danger (r =
      -0.12; P = 0.03) concerning their previously treated prostate cancer. African
      American patients showed greater uncertainty than other ethnic groups (P = 0.005)
      but did not have a greater perception of danger (P = 0.36). Education played a
      major role in uncertainty; patients with lower levels of education tended to
      report higher degrees of uncertainty (r = -0.25; P < 0.001). There was a mild to
      moderate general association between the three outcomes. A greater sense of
      uncertainty was associated with a greater perception of danger (r = 0.34, P <
      0.001), and as danger and uncertainty increased, satisfaction with treatment
      outcome tended to decrease (r was between -0.30 and -0.34, P < 0.001).
      CONCLUSIONS: Results suggest that possible disparities related to patient racial
      background and education may exist in the perception of cancer-related
      uncertainty. Racial and educational disparities, coupled with a mild to moderate
      association of uncertainty or danger perception and overall outcome satisfaction,
      suggest an unmet need for healthcare and nursing services for men undergoing
      treatment for prostate cancer.

PMID- 22985350
TI  - EEG/fMRI fusion based on independent component analysis: integration of data
      driven and model-driven methods.
AB  - Simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) provide complementary noninvasive information of brain activity,
      and EEG/fMRI fusion can achieve higher spatiotemporal resolution than each
      modality separately. This focuses on independent component analysis (ICA)-based
      EEG/fMRI fusion. In order to appreciate the issues, we first describe the
      potential and limitations of the developed fusion approaches: fMRI-constrained
      EEG imaging, EEG-informed fMRI analysis, and symmetric fusion. We then outline
      some newly developed hybrid fusion techniques using ICA and the combination of
      data-/model-driven methods, with special mention of the spatiotemporal EEG/fMRI
      fusion (STEFF). Finally, we discuss the current trend in methodological
      development and the existing limitations for extrapolating neural dynamics.

PMID- 22985351
TI  - Negation without symbols: the importance of recurrence and context in linguistic
      negation.
AB  - A simple recurrent network with a perceptual simulation layer was trained on a
      corpus of affirmative and negated sentences. Linguistic negation can be encoded
      by the network via the inclusion (or absence) of features and categories
      associated with the senses, in one step, without the need for an explicit logical
      operation or for treating the negating word any differently than any other words.
      Visualizing negation as a trajectory in perceptual simulation space is explored
      in detail, and the implications for artificial intelligence, embodied
      computational models, and more practical implications of everyday use of
      negations are discussed.

PMID- 22985349
TI  - Identification of potential mediators of retinotopic mapping: a comparative
      proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice.
AB  - Retinal ganglion cells (RGCs) transmit visual information topographically from
      the eye to the brain, creating a map of visual space in retino-recipient nuclei
      (retinotopy). This process is affected by retinal activity and by activity
      independent molecular cues. Phr1, which encodes a presumed E3 ubiquitin ligase
      (PHR1), is required presynaptically for proper placement of RGC axons in the
      lateral geniculate nucleus and the superior colliculus, suggesting that increased
      levels of PHR1 target proteins may be instructive for retinotopic mapping of
      retinofugal projections. To identify potential target proteins, we conducted a
      proteomic analysis of optic nerve to identify differentially abundant proteins in
      the presence or absence of Phr1 in RGCs. 1D gel electrophoresis identified a
      specific band in controls that was absent in mutants. Targeted proteomic analysis
      of this band demonstrated the presence of PHR1. Additionally, we conducted an
      unbiased proteomic analysis that identified 30 proteins as being significantly
      different between the two genotypes. One of these, heterogeneous nuclear
      ribonucleoprotein M (hnRNP-M), regulates antero-posterior patterning in
      invertebrates and can function as a cell surface adhesion receptor in
      vertebrates. Thus, we have demonstrated that network analysis of quantitative
      proteomic data is a useful approach for hypothesis generation and for identifying
      biologically relevant targets in genetically altered biological models.

PMID- 22985352
TI  - Inhaled pyrazinamide proliposome for targeting alveolar macrophages.
AB  - OBJECTIVE: In this study, pyrazinamide (PZA)-proliposome in a dry powder aerosol
      form was developed for delivering drugs to alveolar macrophages (AMs) infected
      with mycobacteria. MATERIALS AND METHODS: PZA-proliposomes consisting of
      pyrazinamide, soybean phosphatidylcholine, cholesterol and porous mannitol were
      prepared by a spray drying method. The PZA-proliposome physicochemical properties
      were determined using a cascade impactor, X-ray diffraction, differential
      scanning calorimetry and infrared spectroscopy. The toxicity of proliposomes to
      respiratory-associated cell lines (Calu-3, A549 and NR8383) and its potential to
      provoke immunological responses from AMs were determined. In vivo repeated dose
      toxicity in rats was evaluated. RESULTS AND DISCUSSION: PZA-proliposomes were
      successfully prepared. For the aerosolization properties of PZA-proliposomes at
      60 l/min, the powders showed mass median aerodynamic diameters of 4.26-4.39 um,
      with fine particle fractions (aerosolized particles less than 4.4 um) of 20-30%.
      Encapsulation of PZA was 26-45%. PZA-proliposomes were less toxic to respiratory
      associated cells, and did not activate AMs to produce inflammatory mediators,
      including interleukin-1beta, tumor necrosis factor-alpha, and nitric oxide, at a
      toxic level. Renal and liver toxicity in rats were not observed. CONCLUSIONS: We
      suggest that PZA-proliposomes are potential candidates for pulmonary tuberculosis
      treatment.

PMID- 22985353
TI  - Predicting survival in advanced hematologic malignancies: do patient-reported
      symptoms matter?
AB  - OBJECTIVE: To investigate whether patient-reported symptoms provide independent
      prognostic information for survival in patients with hematological malignancies.
      STUDY DESIGN AND SETTING: Overall 119 patients with various diagnoses were
      recruited in an observational study and symptoms were assessed with the M.D.
      Anderson Symptom Inventory (MDASI). Key potential socio-demographic, biomedical,
      and physician-reported prognostic candidates were also considered. The Cox
      proportional hazards regression model was used for both univariate and
      multivariate analyses of survival. Additional sensitivity analysis, based on 500
      bootstrap-generated simulation datasets, was also performed to confirm the
      results obtained with the Cox regression model. RESULTS: The median survival of
      the entire cohort was 4.8 months (range 0-28 months). The MDASI was completed at
      baseline by 91% of patients. The final multivariate model retained two parameters
      as independent prognostic factors for survival: clinical prognostic group and
      patient's self-reported severity of drowsiness. The following hazard ratios (HR)
      were found for curable vs. terminal: 0.055 (95% CI, 0.022-0.136; P < 0.001) and
      0.193 (95% CI, 0.103-0.362: P < 0.001) for advanced vs. terminal. Patient's self
      reported severity of drowsiness independently predicted survival with a HR of
      1.801 (95% CI, 1.044-3.107; P = 0.033). Additional sensitivity analysis confirmed
      the independent prognostic value of variables identified in this study.
      CONCLUSION: The results suggest that patients' self-reporting of symptoms
      provides independent prognostic information for survival in patients with
      hematologic malignancies. These findings underscore the value of collecting
      patient-reported symptom data in routine clinical practice.

PMID- 22985354
TI  - Effect of at-home whitening strips on the surface roughness and color of a
      composite and an ormocer restorative material.
AB  - PURPOSE: Oxygenating agents like carbamide peroxide or H(2) O(2) are commonly
      used whitening agents. They have varying influence on the color and surface
      roughness of resin-based restorative materials and teeth. The aim of this study
      was to evaluate the effect of an at-home peroxide whitening agent applied through
      a whitening strip on the color and surface roughness of a nanofilled composite
      resin and an ormocer-based resin. MATERIALS AND METHODS: Disc-shaped (2 mm thick,
      10 mm diameter) nanofilled resin composite (n = 10) and ormocer (n = 10)
      specimens were prepared. All specimens were treated with a whitening strip.
      Whitening procedures were performed applying a 6.5% hydrogen peroxide whitening
      strip (Crest White Strips Professional) for 30 minutes twice each day for a
      period of 21 consecutive days. During the test intervals, the specimens were
      rinsed under running distilled water for 1 minute to remove the whitening agents
      and immersed in 37 degrees C distilled water until the next treatment. Surface
      roughness and color of the specimens were measured with a profilometer and a
      colorimeter, respectively, before and after whitening. Color changes were
      calculated (DeltaE) using L*, a*, and b* coordinates. Repeated measures of
      variance analysis and Duncan test were used for statistical evaluation (alpha=
      0.05). RESULTS: The average surface roughness of composite increased from 1.4 Ra
      to 2.0 Ra, and from 0.8 Ra to 0.9 Ra for the ormocer material; however, these
      changes in roughness after whitening were not significant (p > 0.05). Also, when
      two materials were compared, the surface roughness of restorative materials was
      not different before and after whitening (p > 0.05). L* and b* values for each
      material changed significantly after whitening (p < 0.05). DeltaE values
      (before/after whitening) calculated for composite (11.9) and ormocer (16.1) were
      not significantly different from each other (p > 0.05). CONCLUSIONS: The tested
      whitening agent did not affect the surface roughness of either resin-based
      restorative material. Both materials became brighter after whitening. The
      behavior of the materials in the yellow/blue axis was opposite to each other
      after whitening. Each material had clinically unacceptable color change after
      whitening (DeltaE > 5.5); however, the magnitude of the color change of materials
      was similar (p > 0.05). According to the results of this study, with the use of
      materials tested, patients should be advised that existing composite restorations
      may bleach along with the natural teeth, and replacement of these restorations
      after whitening may not be required.

PMID- 22985355
TI  - Furan occurrence in starchy food model systems processed at high temperatures:
      effect of ascorbic acid and heating conditions.
AB  - Furan, a potential carcinogen, has been detected in highly consumed starchy
      foods, such as bread and snacks; however, research on furan generation in these
      food matrixes has not been undertaken, thus far. The present study explored the
      effect of ascorbic acid addition and cooking methods (frying and baking) over
      furan occurrence and its relation with the non-enzymatic browning in a wheat
      flour starchy food model system. Results showed that furan generation
      significantly increased in the presence of ascorbic acid after 7 min of heating
      (p < 0.05). The strongest effect was observed for baked products. Additionally,
      the furan content in fried products increased with the increase of the oil uptake
      levels. As for Maillard reactions, in general, the furan level in all samples
      linearly correlated with their degree of non-enzymatic browning, represented by
      L* and a* color parameters (e.g., wheat flour baked samples showed a R(2) of 0.88
      and 0.87 for L* and a*, respectively), when the sample moisture content decreased
      during heating. 

PMID- 22985356
TI  - Site-selective hydrogen-bonding-induced fluorescence quenching of highly
      solvatofluorochromic GFP-like chromophores.
AB  - The unconstrained green fluorescence protein (GFP)-like chromophore m-DMABDI
      displays a high solvatofluorochromicity in aprotic solvents, but the fluorescence
      is quenched in protic solvents. According to the site-specific intramolecularly
      hydrogen-bonded analogs 1OH and 2OH, the hydrogen bonding to the carbonyl oxygen
      is more important than that to the imino nitrogen of the imidazolinone group in
      the fluorescence quenching.

PMID- 22985357
TI  - Extracytoplasmic function (ECF) sigma factor sigmaF is involved in Caulobacter
      crescentus response to heavy metal stress.
AB  - BACKGROUND: The alpha-proteobacterium Caulobacter crescentus inhabits low
      nutrient environments and can tolerate certain levels of heavy metals in these
      sites. It has been reported that C. crescentus responds to exposure to various
      heavy metals by altering the expression of a large number of genes. RESULTS: In
      this work, we show that the ECF sigma factor sigmaF is one of the regulatory
      proteins involved in the control of the transcriptional response to chromium and
      cadmium. Microarray experiments indicate that sigmaF controls eight genes during
      chromium stress, most of which were previously described as induced by heavy
      metals. Surprisingly, sigmaF itself is not strongly auto-regulated under metal
      stress conditions. Interestingly, sigmaF-dependent genes are not induced in the
      presence of agents that generate reactive oxygen species. Promoter analyses
      revealed that a conserved sigmaF-dependent sequence is located upstream of all
      genes of the sigmaF regulon. In addition, we show that the second gene in the
      sigF operon acts as a negative regulator of sigmaF function, and the encoded
      protein has been named NrsF (Negative regulator of sigma F). Substitution of two
      conserved cysteine residues (C131 and C181) in NrsF affects its ability to
      maintain the expression of sigmaF-dependent genes at basal levels. Furthermore,
      we show that sigmaF is released into the cytoplasm during chromium stress and in
      cells carrying point mutations in both conserved cysteines of the protein NrsF.
      CONCLUSION: A possible mechanism for induction of the sigmaF-dependent genes by
      chromium and cadmium is the inactivation of the putative anti-sigma factor NrsF,
      leading to the release of sigmaF to bind RNA polymerase core and drive
      transcription of its regulon.

PMID- 22985358
TI  - Health-related quality of life in girls and boys with juvenile idiopathic
      arthritis: self- and parental reports in a cross-sectional study.
AB  - BACKGROUND: Juvenile Idiopathic Arthritis (JIA) affects children and adolescents
      with both short-term and long-term disability. These children also report lower
      health-related quality of life (HRQOL) compared to their healthy peers. However,
      there seems to be some discrepancies between self- and parent-reports, and gender
      differences need to be further studied. This study aims to describe HRQOL in
      girls and boys with JIA, and to explore gender differences in self-reports
      compared to parent-reports of HRQOL in children with JIA. METHODS: Fifty-three
      children and adolescents with JIA (70% girls and 30% boys) with a median age of
      14 years (8-18 years), and their parents, participated in this cross-sectional
      study in Sweden. Data was systematically collected prior to ordinary visits at a
      Pediatric outpatient clinic, during a period of 16 months (2009-2010). Disability
      was assessed with the Childhood Health Assessment Questionnaire (CHAQ), and
      disease activity by physicians' assessments and Erythrocyte Sedimentation Rate
      (ESR). The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL)
      was used to assess self- and parent-reports of HRQOL in the child. RESULTS: In
      this sample of children with generally low disease activity and mild to moderate
      disability, more than half of the children experienced suboptimal HRQOL, equally
      in girls and boys. Significant differences between self- and parent-reports of
      child HRQOL were most evident among girls, with lower parent-reports regarding
      the girl's physical- and psychosocial health as well as in the total HRQOL score.
      Except for the social functioning subscale, where parents' reports were higher
      compared to their sons, there were no significant differences between boys- and
      parent-reports. CONCLUSIONS: More than half of the girls and boys experienced
      suboptimal HRQOL in this sample, with no gender differences. However, there were
      differences between self- and parent-reports of child HRQOL, with most
      significant differences found among the girls. Thus, differences between self-
      and parent-reports of child HRQOL must be taken into account in clinical
      settings, especially among girls with JIA.

PMID- 22985360
TI  - Patient satisfaction in home health care.
AB  - AIMS AND OBJECTIVES:   To assess the current use of patient satisfaction measures
      in home health care and to examine the reliability and validity of current
      measures of patient satisfaction in home health care. BACKGROUND:   Patient
      satisfaction has been one of the widely used measures in home health care as an
      indicator of quality of care. A few efforts have been made to develop
      psychometrically sound patient satisfaction scales for use in home health care.
      DESIGN:   A critical review of the literature. METHODS:   Electronic databases
      were systematically searched to identify the studies or publications that
      measured and addressed patient satisfaction and its measurement in home health
      care. RESULTS:   The review of the literature showed that patient satisfaction
      measures have been used in the evaluation of care programmes including
      rehabilitation programmes, discharge and home follow-up programmes, care process
      and management practices. Also, patient satisfaction measures were used to
      evaluate new care protocols and treatments. CONCLUSIONS:   Home healthcare
      agencies need valid and reliable patient satisfaction scales. Frameworks of
      patient satisfaction are still in their early developmental stage. Only some of
      the variables related to patient satisfaction are explained by many frameworks.
      RELEVANCE TO CLINICAL PRACTICE:   Home healthcare mangers and researchers need to
      take in consideration the reliability and validity of measures and tools of
      patient satisfaction.

PMID- 22985361
TI  - Human cystathionine beta-synthase (CBS) contains two classes of binding sites for
      S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by
      SAM.
AB  - CBS (cystathionine beta-synthase) is a multidomain tetrameric enzyme essential in
      the regulation of homocysteine metabolism, whose activity is enhanced by the
      allosteric regulator SAM (S-adenosylmethionine). Missense mutations in CBS are
      the major cause of inherited HCU (homocystinuria). In the present study we apply
      a novel approach based on a combination of calorimetric methods, functional
      assays and kinetic modelling to provide structural and energetic insight into the
      effects of SAM on the stability and activity of WT (wild-type) CBS and seven HCU
      causing mutants. We found two sets of SAM-binding sites in the C-terminal
      regulatory domain with different structural and energetic features: a high
      affinity set of two sites, probably involved in kinetic stabilization of the
      regulatory domain, and a low affinity set of four sites, which are involved in
      the enzyme activation. We show that the regulatory domain displays a low kinetic
      stability in WT CBS, which is further decreased in many HCU-causing mutants. We
      propose that the SAM-induced stabilization may play a key role in modulating
      steady-state levels of WT and mutant CBS in vivo. Our strategy may be valuable
      for understanding ligand effects on proteins with a complex architecture and
      their role in human genetic diseases and for the development of novel
      pharmacological strategies.

PMID- 22985362
TI  - HIV type 1 origin and transmission dynamics among different risk groups in
      sardinia: molecular epidemiology within the close boundaries of an Italian
      island.
AB  - In Italy, the HIV-1 epidemic is still mainly sustained by the subtype B genetic
      form, although other and novel subtypes and circulating recombinant forms (CRFs)
      have been reported. A total of 215 HIV-1 pol gene sequences were collected
      between 1992 and 2010. Multiple alignments spanning subtype-specific HIV-1 B pol
      sequences were analyzed by Bayesian phylogenetic methods. Subtype B represented
      90.7% (n=195) of the sequences. Three main clusters were detected. The root of
      the tree dated to 1987. Most of the observed viral gene flow events occurred from
      heterosexual to intravenous drug users (IDUs). Phylogenetic and molecular clock
      analysis showed an early HIV-1 subtype B introduction in the mid-1980s and
      dissemination within local risk-specific clusters. This is the first study to
      describe in detail the HIV-1 molecular epidemiology in one of the largest islands
      in the European basin. The future potential of the Sardinian epidemic as a hub
      between Southern and Northern Europe has to been considered.

PMID- 22985363
TI  - Introduction: Spinal cord injury at the cutting edge of clinical translation: a
      focus issue collaboration between NACTN and AOSpine North America.

PMID- 22985364
TI  - Multicenter clinical research networks for traumatic spinal cord injury: a
      critical pathway to discovery.

PMID- 22985365
TI  - North American Clinical Trials Network for the Treatment of Spinal Cord Injury:
      goals and progress.
AB  - The North American Clinical Trials Network (NACTN) for the Treatment of Spinal
      Cord Injury is a consortium of 10 neurosurgery departments, a data management
      center, and a pharmacological center. The NACTN was established with the goal of
      bringing recent molecular and cell-based discoveries in neuroprotection and
      regeneration from the laboratory into clinical trials that optimize meaningful
      data outcomes and maximum safety to patients. The requirements of planning and
      executing clinical trials in spinal cord injury (SCI) and the steps that the
      NACTN has taken to address these requirements are discussed and illustrated in
      articles in this issue of the Journal of Neurosurgery: Spine. The progress that
      the NACTN has made in meeting these goals can be summarized as organizing a
      network of hospitals capable of enrolling a sufficient number of patients for
      conducting Phase I and II trials; creating a Data Management Center and a
      database of the natural history of recovery after SCI (at the time of this
      writing 485 patients were enrolled in the database); creating a database of the
      incidence and severity of complications that occur during acute and subacute
      treatment after SCI; developing a Pharmacological Center capable of performing
      pharmacokinetic and pharmacodynamic studies of therapeutic drugs; completing
      enrollment of 36 patients in NACTN's first clinical trial, a Phase I study of
      riluzole, a neuroprotective drug; and performing pharmacokinetic and
      pharmacodynamic studies of riluzole in acute SCI.

PMID- 22985366
TI  - Clinical predictors of neurological outcome, functional status, and survival
      after traumatic spinal cord injury: a systematic review.
AB  - OBJECT: The object of this study was to identify, by means of a systematic review
      of the literature, the acute clinical predictors of neurological outcome,
      functional outcome, and survival after traumatic spinal cord injury (SCI).
      METHODS: A comprehensive computerized literature review search was performed,
      using MEDLINE, PubMed, EMBASE, CINAHL, and the Cochrane Database of Systematic
      Reviews. Selected articles were classified according to their level of evidence.
      Articles were then stratified into one of 3 domains depending on whether the
      primary focus was clinical prediction of 1) neurological outcome, 2) functional
      status, or 3) survival. For each study selected, clinical predictors related to
      patient demographic characteristics, injury mechanism, or neurological
      examination findings were extracted, and the individual relationship to outcome
      was defined. RESULTS: The initial search resulted in 376 citations. After
      application of the inclusion and exclusion criteria and study review, 51 relevant
      articles were identified and graded. Of these, 25 provided predictors for
      neurological outcome, 22 for functional outcome, and 15 for survival, with
      several of the articles providing information on more than one type of outcome.
      All of the included studies were designated as providing Class I, II, or III
      levels of evidence. The severity of neurological injury (as measured by admission
      Americal Spinal Injury Association Impairment Scale grade, Frankel grade, or
      injury completeness), level of injury, and the presence of a zone of partial
      preservation were consistent predictors of neurological outcome. Severity of
      neurological injury, level of injury, reflex pattern, and age were consistent
      predictors of functional outcome. Finally, severity of neurological injury, level
      of injury, age, and the presence of multisystem trauma seen with higher-energy
      injury mechanisms were consistent predictors of survival. CONCLUSIONS: On the
      basis on this review, the authors have identified a constellation of acute
      clinical features that may help to define an individual's profile for recovery
      and survival after SCI. This study will help to facilitate communication in the
      clinical realm and assist in classifying subsets of patients within future
      clinical studies.

PMID- 22985367
TI  - Assessing quality of life in traumatic spinal cord injury: an evolving landscape.

PMID- 22985368
TI  - Quality of life in persons with spinal cord injury: comparisons with other
      populations.
AB  - OBJECT: The aim of this study was to identify the quality of life (QOL) measures
      commonly used to assess patients with spinal cord injury (SCI) and to summarize
      studies using common QOL measures that have been validated in SCI populations to
      compare scores in persons with SCI with those in a control population. METHODS: A
      systematic search of PubMed was conducted to identify studies using common QOL
      measures in persons with SCI and those comparing scores for QOL measures in an
      SCI population with scores in other populations. The authors sought comparative
      studies utilizing QOL measures for which validity and reliability analyses had
      been done. RESULTS: Of 28 QOL measures found, validity and reliability studies
      had been conducted in patients with SCI for 5 measures. Twelve comparative
      studies compared QOL in SCI patients with QOL in healthy controls or in patients
      with other disabilities, or with normative data. The 36-Item Short Form Health
      Survey (SF-36) and the short version of the WHOQOL (WHOQOL-BREF) were the most
      widely used QOL instruments. Patients with SCI had a decreased QOL as compared
      with that in healthy controls or normative data, with the most pronounced
      deficits in the domains of physical functioning and physical role limitations. In
      3 studies, patients with tetraplegia had a lower physical domain QOL than did
      those with paraplegia. Overall, however, the impact of injury level and injury
      completeness on QOL after SCI remains unclear due to a lack of longitudinal
      studies. CONCLUSIONS: The SF-36 and WHOQOL-BREF are validated instruments that
      should be considered for use in SCI QOL studies. Future analysis of deficits in
      QOL among patients with SCI would benefit from the development of a QOL
      instrument specifically targeted to SCI. Longitudinal studies to assess the
      impact of injury level and injury completeness on SCI QOL are also needed.

PMID- 22985369
TI  - Predictors of pulmonary complications in blunt traumatic spinal cord injury.
AB  - OBJECT: Pulmonary complications are the most common acute systemic adverse events
      following spinal cord injury (SCI), and contribute to morbidity, mortality, and
      increased length of hospital stay (LOS). Identification of factors associated
      with pulmonary complications would be of value in prevention and acute care
      management. Predictors of pulmonary complications after SCI and their effect on
      neurological recovery were prospectively studied between 2005 and 2009 at the 9
      hospitals in the North American Clinical Trials Network (NACTN). METHODS: The
      authors sought to address 2 specific aims: 1) define and analyze the predictors
      of moderate and severe pulmonary complications following SCI; and 2) investigate
      whether pulmonary complications negatively affected the American Spinal Injury
      Association (ASIA) Impairment Scale conversion rate of patients with SCI. The
      NACTN registry of the demographic data, neurological findings, imaging studies,
      and acute hospitalization duration of patients with SCI was used to analyze the
      incidence and severity of pulmonary complications in 109 patients with early MR
      imaging and long-term follow-up (mean 9.5 months). Univariate and Bayesian
      logistic regression analyses were used to analyze the data. RESULTS: In this
      study, 86 patients were male, and the mean age was 43 years. The causes of injury
      were motor vehicle accidents and falls in 80 patients. The SCI segmental level
      was in the cervical, thoracic, and conus medullaris regions in 87, 14, and 8
      patients, respectively. Sixty-four patients were neurologically motor complete at
      the time of admission. The authors encountered 87 complications in 51 patients:
      ventilator-dependent respiratory failure (26); pneumonia (25); pleural effusion
      (17); acute lung injury (6); lobar collapse (4); pneumothorax (4); pulmonary
      embolism (2); hemothorax (2), and mucus plug (1). Univariate analysis indicated
      associations between pulmonary complications and younger age, sports injuries,
      ASIA Impairment Scale grade, ascending neurological level, and lesion length on
      the MRI studies at admission. Bayesian logistic regression indicated a
      significant relationship between pulmonary complications and ASIA Impairment
      Scale Grades A (p = 0.0002) and B (p = 0.04) at admission. Pulmonary
      complications did not affect long-term conversion of ASIA Impairment Scale
      grades. CONCLUSIONS: The ASIA Impairment Scale grade was the fundamental clinical
      entity predicting pulmonary complications. Although pulmonary complications
      significantly increased LOS, they did not increase mortality rates and did not
      adversely affect the rate of conversion to a better ASIA Impairment Scale grade
      in patients with SCI. Maximum canal compromise, maximum spinal cord compression,
      and Acute Physiology and Chronic Health Evaluation-II score had no relationship
      to pulmonary complications.

PMID- 22985370
TI  - Clinical prediction model for acute inpatient complications after traumatic
      cervical spinal cord injury: a subanalysis from the Surgical Timing in Acute
      Spinal Cord Injury Study.
AB  - OBJECT: While the majority of existing reports focus on complications sustained
      during the chronic stages after traumatic spinal cord injury (SCI), the objective
      in the current study was to characterize and quantify acute inpatient
      complications. In addition, the authors sought to create a prediction model using
      clinical variables documented at hospital admission to predict acute complication
      development. METHODS: Analyses were based on data from the Surgical Timing in
      Acute Spinal Cord Injury Study (STASCIS) data registry, which contains
      prospective information on adult patients with cervical SCIs who were enrolled at
      6 North American centers over a 7-year period. All patients who underwent a
      standardized American Spinal Injury Association (ASIA) neurological examination
      within 24 hours of injury and whose follow-up information was available at the
      acute hospital discharge were included in the study. For purposes of
      classification, complications were divided into 5 major categories: 1)
      cardiopulmonary, 2) surgical, 3) thrombotic, 4) infectious, and 5) decubitus
      ulcer development. Univariate statistical analyses were performed to determine
      the relationship between complication occurrence and individual demographic,
      injury, and treatment variables. Multivariate logistic regression was
      subsequently performed to create a complication prediction model. Model
      discrimination was judged according to the area under the receiver operating
      characteristic curve. RESULTS: Complete complication information was available
      for 411 patients at the acute care discharge. One hundred sixty patients (38.9%)
      experienced 240 complications. The mean age among those who experienced at least
      one complication was 45.9 years, as compared with 43.5 years among those who did
      not have a complication (p = 0.18). In the univariate analysis, patients with
      complications were less likely to receive steroids at admission (p = 0.01), had a
      greater severity of neurological injury as indicated by the ASIA Impairment Scale
      (AIS) grade at presentation (p < 0.01), and a higher frequency of significant
      comorbidity (p = 0.04). In a multivariate logistic regression model, a severe
      initial AIS grade (p < 0.01), a high-energy injury mechanism (p = 0.07), an older
      age (p = 0.05), the absence of steroid administration (p = 0.02), and the
      presence of comorbid illness (p = 0.02) were associated with a greater likelihood
      of complication development during the period of acute hospitalization. The area
      under the curve value for the full model was 0.75, indicating acceptable
      predictive discrimination. CONCLUSIONS: These results will help clinicians to
      identify patients with cervical SCIs at greatest risk for complication
      development and thus allowing for the institution of aggressive complication
      prevention measures.

PMID- 22985371
TI  - What do we currently know about thoracic spinal cord injury recovery and
      outcomes? A systematic review.
AB  - OBJECT: The purpose of this paper was to systematically review and critically
      appraise the evidence for whether there are differences in outcomes or recovery
      after thoracic spinal cord injuries (SCIs) based on the spinal level, the timing
      of intervention, or cause of SCI. METHODS: Systematic searches were conducted
      using PubMed/MEDLINE through January 5, 2012. From 486 articles identified, 10
      included data on the population of interest. Included studies were assigned a
      level of evidence (LOE) rating based on study quality, and an overall strength of
      evidence was assessed. To estimate the effect of injury level on patient
      outcomes, the relative risk and risk difference were calculated when data were
      available. RESULTS: From 486 citations identified, 3 registry studies and 7
      retrospective cohort studies met the inclusion criteria. All were rated as being
      of poor quality (LOE III). Limited literature exists on the epidemiology of
      traumatic and nontraumatic SCI. Few studies evaluated outcomes based on SCI level
      within the thoracic spine. Pulmonary complications and thromboembolic events were
      less common in persons with lower thoracic SCI (T7-12) than in those with higher
      thoracic SCI (T1-6) in 2 large studies, but no differences were found in
      functional outcomes in 4 smaller studies. Patients undergoing earlier surgery (<
      72 hours) may have fewer ventilator, ICU, and hospital days than those undergoing
      later surgery. One small study of SCI during repair of aortic aneurysm compared
      with traumatic SCI reported similar outcomes for both groups. There are
      substantial deficiencies in the scientific literature on thoracic SCI in regard
      to assessment, outcomes ratings, and effectiveness of therapy. CONCLUSIONS: The
      overall strength of evidence for all outcomes reported is low. Definitive
      conclusions should not be drawn regarding the prognosis for outcome and recovery
      after thoracic SCI. From a physiological standpoint, additional methodologically
      rigorous studies that take into consideration various levels of injury in more
      anatomically and physiologically relevant form are needed. Use of validated,
      comprehensive outcomes tools are important to improve our understanding of the
      impact of thoracic SCI and aid in examining factors in recovery from thoracic
      SCI.

PMID- 22985372
TI  - Development of the Graded Redefined Assessment of Strength, Sensibility and
      Prehension (GRASSP): reviewing measurement specific to the upper limb in
      tetraplegia.
AB  - OBJECT: Primary outcome measures for the upper limb in trials concerning human
      spinal cord injury (SCI) need to distinguish between functional and neurological
      changes and require satisfying psychometric properties for clinical application.
      METHODS: The Graded Redefined Assessment of Strength, Sensibility and Prehension
      (GRASSP) was developed by the International GRASSP Research and Design Team as a
      clinical outcome measure specific to the upper limbs for individuals with
      complete and incomplete tetraplegia (that is, paralysis or paresis). It can be
      administered across the continuum of recovery after acute cervical SCI. An
      international multicenter study (involving centers in North America and Europe)
      was conducted to apply the measure internationally and examine its applicability.
      RESULTS: The GRASSP is a multimodal test comprising 5 subtests for each upper
      limb: dorsal sensation, palmar sensation (tested with Semmes-Weinstein
      monofilaments), strength (tested with motor grading of 10 muscles), and
      prehension (distinguishes scores for qualitative and quantitative grasping).
      Thus, administration of the GRASSP results in 5 numerical scores that provide a
      comprehensive profile of upper-limb function. The established interrater and test
      retest reliability for all subtests within the GRASSP range from 0.84 to 0.96 and
      from 0.86 to 0.98, respectively. The GRASSP is approximately 50% more sensitive
      (construct validity) than the International Standards of Neurological
      Classification of SCI (ISNCSCI) in defining sensory and motor integrity of the
      upper limb. The subtests show concurrence with the Spinal Cord Independence
      Measure (SCIM), SCIM self-care subscales, and Capabilities of Upper Extremity
      Questionnaire (CUE) (the strongest concurrence to impairment is with self
      perception of function [CUE], 0.57-0.83, p < 0.0001). CONCLUSIONS: The GRASSP was
      found to demonstrate reliability, construct validity, and concurrent validity for
      use as a standardized upper-limb impairment measure for individuals with complete
      or incomplete tetraplegia. Responsiveness (follow-up from onset to 1 year
      postinjury) is currently being tested in international studies (in North America
      and Europe). The GRASSP can be administered early after injury, thus making it a
      tool that can be administered in acute care (in the ICU), rehabilitation, and
      outpatient clinics.

PMID- 22985373
TI  - Quantitative and sensitive assessment of neurophysiological status after human
      spinal cord injury.
AB  - OBJECT: This study was designed to develop an objective and sensitive spinal cord
      injury (SCI) characterization protocol based on surface electromyography (EMG)
      activity. METHODS: Twenty-four patients at both acute and chronic time points
      post-SCI, as well as 4 noninjured volunteers, were assessed using
      neurophysiological and clinical measures of volitional motor function. The EMG
      amplitude was recorded from 15 representative muscles bilaterally during
      standardized maneuvers as a neurophysiological assessment of voluntary motor
      function. International Standards for the Neurological Classification of Spinal
      Cord Injury (ISNCSCI) examinations were performed as a clinical assessment of
      lesion severity. RESULTS: Sixty-six functional neurophysiological assessments
      were performed in 24 patients with SCI and in 4 neurologically intact
      individuals. The collected EMG data were organized by quantitative parameters and
      statistically analyzed. The correlation between root mean square (RMS) of the EMG
      signals and ISNCSCI motor score was confirmed by Kendall correlation analysis.
      The Kendall correlation value between overall muscles/levels, motor scores, and
      the RMS of the EMG data is 0.85, with the 95% CI falling into the range of 0.76
      0.95. Significant correlations were also observed for the soleus (0.51 [0.28
      0.74]), tibialis anterior (TA) (0.53 [0.33-0.73]), tricep (0.52, [0.34-0.70]),
      and extensor carpi radialis (ECR) (0.80 [0.42-1.00]) muscles. Comparisons of RMS
      EMG values in groups defined by ISNCSCI motor score further confirmed these
      results. At the bicep and ECR, patients with motor scores of 5 had nearly
      significantly higher RMS EMG values than patients with motor scores of 0 (p =
      0.059 and 0.052, respectively). At the soleus and TA, the RMS of the EMG value
      was significantly higher (p < 0.01) for patients with American Spinal Injury
      Association Impairment Scale motor scores of 5 than for those with ISNCSCI motor
      scores of 0. Those with C-7 ISNCSCI motor scores of 5 had significantly higher
      RMS EMG values at the tricep than those with motor scores of 4 (p = 0.008) and 0
      (p = 0.02). Results also show that surface EMG signals recorded from trunk
      muscles allowed the examiner to pick up subclinical changes, even though no
      ISNCSCI scores were given. CONCLUSIONS: Surface EMG signal is suitable for
      objective neurological SCI characterization protocol design. The quantifiable
      features of surface EMG may increase SCI characterization resolution by adding
      subclinical details to the clinical picture of lesion severity and distribution.

PMID- 22985374
TI  - Cervical spondylotic myelopathy.

PMID- 22985375
TI  - Is surgery for cervical spondylotic myelopathy cost-effective? A cost-utility
      analysis based on data from the AOSpine North America prospective CSM study.
AB  - OBJECT: Surgical intervention for appropriately selected patients with cervical
      spondylotic myelopathy (CSM) has demonstrated favorable outcomes. This study
      evaluates the cost-effectiveness of this type of surgery in terms of cost per
      quality-adjusted life year (QALY) gained. METHODS: As part of a larger
      prospective multicenter study, the direct costs of medical treatment for 70
      patients undergoing surgery for CSM at a single institution in Canada were
      retrospectively obtained from the hospital expenses database and physician
      reimbursement data. Utilities were estimated on the entire sample of 278 subjects
      enrolled in the multicenter study using SF-6D-derived utilities from 12- and 24
      month SF-36v2 follow-up information. Costs were analyzed from the payer
      perspective. A 10-year horizon with 3% discounting was applied to health
      utilities estimates. Sensitivity analysis was performed by varying utility gain
      by 20%. RESULTS: The SF-6D utility gain was 0.0734 (95% CI 0.0557-0.0912, p <
      0.01) at 12 months and remained unchanged at 24 months. The 10-year discounted
      QALY gain was 0.64. Direct costs of medical treatment were estimated at an
      average of CaD $21,066. The estimated cost-utility ratio was CaD $32,916 per QALY
      gained. The sensitivity analysis showed a range of CaD $27,326-$40,988 per QALY
      gained. These estimates are within the limits for medical procedures that have an
      acceptable cost-utility ratio. CONCLUSIONS: Surgical treatment for CSM is
      associated with significant improvement in health utilities as measured by the SF
      6D. The direct cost of medical treatment per QALY gained places this form of
      treatment within the category deemed by payers to be cost-effective.

PMID- 22985376
TI  - Optimization of the decision-making process for the selection of therapeutics to
      undergo clinical testing for spinal cord injury in the North American Clinical
      Trials Network.
AB  - The North American Clinical Trials Network (NACTN) includes 9 clinical centers
      funded by the US Department of Defense and the Christopher Reeve Paralysis
      Foundation. Its purpose is to accelerate clinical testing of promising
      therapeutics in spinal cord injury (SCI) through the development of a robust
      interactive infrastructure. This structure includes key committees that serve to
      provide longitudinal guidance to the Network. These committees include the
      Executive, Data Management, and Neurological Outcome Assessments Committees, and
      the Therapeutic Selection Committee (TSC), which is the subject of this
      manuscript. The NACTN brings unique elements to the SCI field. The Network's
      stability is not restricted to a single clinical trial. Network members have
      diverse expertise and include experts in clinical care, clinical trial design and
      methodology, pharmacology, preclinical and clinical research, and advanced
      rehabilitation techniques. Frequent systematic communication is assigned a high
      value, as is democratic process, fairness and efficiency of decision making, and
      resource allocation. This article focuses on how decision making occurs within
      the TSC to rank alternative therapeutics according to 2 main variables: quality
      of the preclinical data set, and fit with the Network's aims and capabilities.
      This selection process is important because if the Network's resources are
      committed to a therapeutic, alternatives cannot be pursued. A proposed
      methodology includes a multicriteria decision analysis that uses a Multi
      Attribute Global Inference of Quality matrix to quantify the process. To rank
      therapeutics, the TSC uses a series of consensus steps designed to reduce
      individual and group bias and limit subjectivity. Given the difficulties
      encountered by industry in completing clinical trials in SCI, stable
      collaborative not-for-profit consortia, such as the NACTN, may be essential to
      clinical progress in SCI. The evolution of the NACTN also offers substantial
      opportunity to refine decision making and group dynamics. Making the best
      possible decisions concerning therapeutics selection for trial testing is a
      cornerstone of the Network's function.

PMID- 22985377
TI  - A systematic review of spinal fMRI research: outlining the elements of
      experimental design.
AB  - OBJECT: Since the first published report of spinal functional MRI (fMRI) in
      humans in 1996, this body of literature has grown substantially. In the present
      article, the authors systematically review all spinal fMRI studies conducted in
      healthy individuals with a focus on the different motor and sensory paradigms
      used and the results acquired. METHODS: The authors conducted a systematic search
      of MEDLINE for literature published from 1990 through November 2011 reporting on
      stimulation paradigms used to assess spinal fMRI scans in healthy individuals.
      RESULTS: They identified 19 peer-reviewed studies from 1996 to the present in
      which a combination of different spinal fMRI methods were used to investigate the
      spinal cord in healthy individuals. Eight of the studies used a motor stimulation
      paradigm, 10 used a sensory stimulation paradigm, and 1 compared motor and
      sensory stimulation paradigms. CONCLUSIONS: Despite differences in the results of
      various studies, even when similar stimulation paradigms were used, this body of
      literature underscores that spinal fMRI signals can be obtained from the human
      spinal cord. The authors intend this review to serve as an introduction to spinal
      fMRI research and what it may offer the field of spinal cord injury research.

PMID- 22985379
TI  - Pharmacology of riluzole in acute spinal cord injury.
AB  - OBJECT: The aim of this paper was to characterize individual and population
      pharmacokinetics of enterally administered riluzole in a Phase 1 clinical trial
      of riluzole as a neuroprotective agent in adults 18-70 years old with acute
      spinal cord injury (SCI). METHODS: Thirty-five individuals with acute SCI,
      American Spinal Injury Association Impairment Scale Grades A-C, neurological
      levels from C-4 to T-12, who were enrolled in the Phase 1 clinical trial
      sponsored by the North American Clinical Trials Network for Treatment of Spinal
      Cord Injury, received 50 mg riluzole twice daily for 28 doses. The first dose was
      administered at a mean of 8.7 +/- 2.2 hours postinjury. Trough plasma samples
      were collected within 1 hour predose, and peak plasma samples were collected 2
      hours postdose on Days 3 and 14 of treatment. Riluzole concentrations were
      quantified by high-performance liquid chromatography assay. The data were
      analyzed for individual and population pharmacokinetics using basic structural
      and covariate models. The pharmacokinetic measures studied were the peak
      concentration (C(max)), trough concentration (C(min)), systemic exposure (AUC(0
      12)), clearance (CL/F), and volume of distribution (V_F) normalized by the
      bioavailability (F). RESULTS: The C(max) and AUC(0-12) achieved in SCI patients
      were lower than those in ALS patients on the same dose basis, due to a higher CL
      and larger V. The pharmacokinetics of riluzole (C(max), C(min), AUC(0-12), CL,
      and V) changed during the acute and subacute phases of SCI during the 14 days of
      therapy. It was consistently observed in patients at all clinical sites that
      C(max), C(min), and AUC(0-12) (128.9 ng/ml, 45.6 ng/ml, and 982.0 ng * hr/ml,
      respectively) were significantly higher on Day 3 than on Day 14 (76.5 ng/ml, 19.1
      ng/ml, and 521.0 ng * hr/ml, respectively). These changes resulted from lower CL
      (49.5 vs 106.2 L/hour) and smaller V (557.1 vs 1297.9/L) on Day 3. No fluid
      imbalance or cytochrome P 1A2 induction due to concomitant medications was
      identified during the treatment course to account for such increases in V and CL,
      respectively. Possible mechanisms underlying these changes are discussed.
      CONCLUSIONS: This is the first report of clinical pharmacokinetics of riluzole in
      patients with SCI. The C(max) and AUC(0-12) achieved in SCI patients were lower
      than those in ALS patients on the same dose basis, due to a higher clearance and
      larger volume of distribution in SCI patients. The finding in SCI patients of an
      increase in the clearance and distribution of riluzole between the 3rd and 14th
      days after SCI, with a lower plasma concentration of riluzole on the 14th day,
      stresses the importance of monitoring changes in drug metabolism after SCI in
      interpreting the safety and efficacy of therapeutic drugs that are used in
      clinical trials in SCI. Clinical trial registration no.: NCT00876889.

PMID- 22985378
TI  - Incidence and severity of acute complications after spinal cord injury.
AB  - OBJECT: The aim of this multicenter, prospective study was to determine the
      spectrum, incidence, and severity of complications during the initial
      hospitalization of patients with spinal cord injury. METHODS: The study was
      conducted at 9 university-affiliated hospitals that comprise the clinical centers
      of the North American Clinical Trials Network (NACTN) for Treatment of Spinal
      Cord Injury. The study population comprised 315 patients admitted to NACTN
      clinical centers between June 25, 2005, and November 2, 2010, who had American
      Spinal Injury Association (ASIA) Impairment Scale grades of A-D and were 18 years
      of age or older. Patients were managed according to a standardized protocol.
      RESULTS: The study population was 79% male with a median age of 44 years. The
      leading causes of injury were falls (37%) and motor vehicle accidents (28%). The
      distribution of initial ASIA grades were A (40%), B (16%), C (15%), and D (29%).
      Fifty-eight percent of patients sustained 1 or more severe, moderate, or mild
      complications. Complications were associated with more severe ASIA grade: 84% of
      patients with Grade A and 25% of patients with Grade D had at least 1
      complication. Seventy-eight percent of complications occurred within 14 days of
      injury. The most frequent types of severe and moderate complications were
      respiratory failure, pneumonia, pleural effusion, anemia, cardiac dysrhythmia,
      and severe bradycardia. The mortality rate was 3.5% and was associated with
      increased age and preexisting morbidity. CONCLUSIONS: Knowledge of the type,
      frequency, time of occurrence, and severity of specific complications that occur
      after spinal cord injury can aid in their early detection, treatment, and
      prevention. The data are of importance in evaluating and selecting therapy for
      clinical trials.

PMID- 22985380
TI  - Quantitative testing in spinal cord injury: overview of reliability and
      predictive validity.
AB  - OBJECT: The objective of this study was to identify commonly used physiological
      outcome measures and summarize evidence on the reliability and predictive
      validity of quantitative measures used in monitoring persons with spinal cord
      injury (SCI). METHODS: A systematic search of PubMed through January 5, 2012, was
      conducted to identify publications using common outcome measures in persons with
      SCI and for studies that were specifically designed to evaluate the reliability
      and predictive validity of selected quantitative measures. Quantitative measures
      were defined as tests that quantify sensory and motor function, such as amount of
      force or torque, as well as thresholds, amplitudes, and latencies of evoked
      potentials that might be useful in studies and monitoring of patients with SCI.
      Reliability studies reporting interclass correlation coefficients (ICCs) or
      weighted kappa coefficients were considered for inclusion. Studies explicitly
      evaluating correlation between measures and specific functional outcomes were
      considered for predictive validity. RESULTS: From a total of 121 potentially
      relevant citations, 6 studies of reliability and 4 studies of predictive validity
      for quantitative tests met the inclusion criteria. In persons with incomplete
      SCI, ICCs for both interrater and intrarater reliability of electrical perceptual
      threshold (EPT) were >= 0.7 above the sensory level of SCI but were less reliable
      below the sensory level. Interclass correlation coefficients for interrater and
      intrarater reliability of the Graded Redefined Assessment of Strength,
      Sensibility, and Prehension (GRASSP) components ranged from 0.84 to 0.98. For
      electromyography, the ICC was consistently high for within-day tests. The overall
      quality of reliability of the majority of studies was poor, due to the potential
      for selection bias and small sample sizes. No classic validation studies were
      found for the selected measures, and evidence regarding the predictive validity
      of the measures was limited. Somatosensory evoked potentials (SSEPs) may be
      correlated with ambulatory capacity, as well as the Barthel Index and motor index
      scores, but this correlation was limited for evaluation of bladder function
      recovery in 3 studies that assessed the correlation between baseline or initial
      SSEPs and a specific clinical outcome at a later follow-up time. All studies used
      convenience samples and the overall sample quality was low. CONCLUSIONS: Evidence
      on the reliability and validity of the quantitative measures selected for this
      review is limited, and the overall quality of existing studies is poor. There is
      some evidence for the reliability of the EPT, dermatomal SSEPs, and the GRASSP to
      suggest that they may be useful in longitudinal studies of patients with SCI.
      There is a need for high quality studies of reliability, responsiveness, and
      validity for quantitative measures to monitor the level and degree of SCI.

PMID- 22985381
TI  - Riluzole for the treatment of acute traumatic spinal cord injury: rationale for
      and design of the NACTN Phase I clinical trial.
AB  - In the immediate period after traumatic spinal cord injury (SCI) a variety of
      secondary injury mechanisms combine to gradually expand the initial lesion size,
      potentially leading to diminished neurological outcomes at long-term follow-up.
      Riluzole, a benzothiazole drug, which has neuroprotective properties based on
      sodium channel blockade and mitigation of glutamatergic toxicity, is currently an
      approved drug that attenuates the extent of neuronal degeneration in patients
      with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies
      have associated riluzole administration with improved functional outcomes and
      increased neural tissue preservation. Based on these findings, riluzole has
      attracted considerable interest as a potential neuroprotective drug for the
      treatment of SCI. Currently, a Phase I trial evaluating the safety and
      pharmacokinetic profile of riluzole in human SCI patients is being conducted by
      the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord
      Injury. The current review summarizes the existing preclinical and clinical
      literature on riluzole, provides a detailed description of the Phase I trial, and
      suggests potential opportunities for future investigation. Clinical trial
      registration no.: NCT00876889.

PMID- 22985382
TI  - Translational potential of preclinical trials of neuroprotection through
      pharmacotherapy for spinal cord injury.
AB  - There is a need to enhance the pipeline of discovery and evaluation of
      neuroprotective pharmacological agents for patients with spinal cord injury
      (SCI). Although much effort and money has been expended on discovering effective
      agents for acute and subacute SCI, no agents that produce major benefit have been
      proven to date. The deficiencies of all aspects of the pipeline, including the
      basic science input and the clinical testing output, require examination to
      determine remedial strategies. Where has the neuroprotective/pharmacotherapy
      preclinical process failed and what needs to be done to achieve success? These
      are the questions raised in the present review, which has 2 objectives: 1)
      identification of articles that address issues related to the translational
      readiness of preclinical SCI pharmacological therapies; and 2) examination of the
      preclinical studies of 5 selected agents evaluated in animal models of SCI
      (including blunt force trauma, penetrating trauma, or ischemia). The 5 agents
      were riluzole, glyburide, magnesium sulfate, nimodipine, and minocycline, and
      these were selected because of their promise of translational readiness as
      determined by the North American Clinical Trials Network Consortium.   The
      authors found that there are major deficiencies in the effort that has been
      extended to coordinate and conduct preclinical neuroprotection/pharmacotherapy
      trials in the SCI field. Apart from a few notable exceptions such as the NIH
      effort to replicate promising strategies, this field has been poorly coordinated.
      Only a small number of articles have even attempted an overall evaluation of the
      neuroprotective/pharmacotherapy agents used in preclinical SCI trials. There is
      no consensus about how to select the agents for translation to humans on the
      basis of their preclinical performance and according to agreed-upon preclinical
      performance criteria.   In the absence of such a system and to select the next
      agent for translation, the Consortium has developed a Treatment Strategy
      Selection Committee, and this committee selected the most promising 5 agents for
      potential translation. The results show that the preclinical work on these 5
      agents has left numerous gaps in knowledge about their preclinical performance
      and confirm the need for significant changes in preclinical
      neuroprotection/pharmacotherapy trials in SCI. A recommendation is made for the
      development and validation of a preclinical scoring system involving worldwide
      experts in preclinical and clinical SCI.

PMID- 22985383
TI  - Evaluation of clinical experience using cell-based therapies in patients with
      spinal cord injury: a systematic review.
AB  - OBJECT: Using a systematic approach, the authors evaluated the current
      utilization, safety, and effectiveness of cellular therapies for traumatic spinal
      cord injuries (SCIs) in humans. METHODS: A systematic search and critical review
      of the literature published through mid-January 2012 was performed. Articles
      included in the search were restricted to the English language, studies with at
      least 10 patients, and those analyzing cellular therapies for traumatic SCI.
      Citations were evaluated for relevance using a priori criteria, and those that
      met the inclusion criteria were critically reviewed. Each article was then
      designated a level of evidence that was developed by the Oxford Centre for
      Evidence-Based Medicine. RESULTS: The initial literature search identified 651
      relevant articles, which decreased to 350 after excluding case reports and
      reviews. Evaluation of articles at the title/abstract level, and later at the
      full-text level, limited the final article set to 12 papers. The following
      cellular therapies employed in humans with SCI are reviewed: bone marrow
      mesenchymal and hematopoietic stem cells (8 studies), olfactory ensheathing cells
      (2 studies), Schwann cells (1 study), and fetal neurogenic tissue (1 study).
      Overall the quality of the literature was very low, with 3 Grade III levels of
      evidence and 9 Grade IV studies. CONCLUSIONS: Several different cellular-mediated
      strategies for adult SCI have been reported to be relatively safe with varying
      degrees of neurological recovery. However, the literature is of low quality and
      there is a need for improved preclinical studies and prospective, controlled
      clinical trials.

PMID- 22985384
TI  - Form(s) in the patient-centered medical home.
AB  - Care plans are becoming a focus of conversation and development in primary care
      as the patient-centered medical home is developing in the various states. In this
      issue, there are two accounts of attempts to develop and implement such
      generative processes through the use of a form. (PsycINFO Database Record (c)
      2012 APA, all rights reserved).

PMID- 22985385
TI  - A medical home: changing the way patients and teams relate through patient
      centered care plans.
AB  - The patient-centered medical home model incorporates patient-centered care as a
      central tenet and espouses the health care team partnering with an engaged
      patient. The tools to accomplish this type of care have not evolved along with
      these values. This report describes how the adoption and use of a patient
      centered care plan (PCCP) document enhanced care for complex patients and changed
      the relationships with health team members. The PCCP was used in a residency
      affiliated community hospital, group family medicine site and provided patient
      centered, goal-directed care for complex patients. Use of the PCCP changed the
      patient-team relationship, showing that this care plan document can support the
      practice of the patient-centered medical home model by enhancing patient
      centered, coordinated, comprehensive care. (PsycINFO Database Record (c) 2012
      APA, all rights reserved).

PMID- 22985386
TI  - Establishing the Collaborative Care Research Network (CCRN): a description of
      initial participating sites.
AB  - Collaborative care has increased dramatically in the past decade, yet the
      variability in collaborative strategies and the diversity of settings in which
      collaboration is being implemented make it difficult to assess quality and
      outcomes. Therefore, three aims were addressed in the current study: (a) describe
      and characterize the sites in the Collaborative Care Research Network (CCRN), (b)
      identify factors associated with practices' self-identified collaborative care
      model (e.g., coordinated, integrated, care management), and (c) identify
      limitations of available survey data elements so as to propose additional
      elements for future surveys. Initial (CCRN) sites completed surveys regarding
      several organizational factors (e.g., setting type, size of patient population,
      number of behavioral health providers). Results from 39 sites showed significant
      heterogeneity in self-identified type of collaborative care model practiced
      (e.g., integrated care, coordinated care), type of practice setting (e.g.,
      academic, federally qualified health center, military), size of clinic, and ratio
      of behavioral health providers to medical providers. This diversity in network
      site characteristics can provide a rich platform to address a number of questions
      regarding the current practice of collaborative care. Recommendations are made to
      improve future surveys to better understand elements of the patient-centered
      medical home and the role it may play in outcomes. (PsycINFO Database Record (c)
      2012 APA, all rights reserved).

PMID- 22985388
TI  - Can the impact of gender equality on health be measured? A cross-sectional study
      comparing measures based on register data with individual survey-based data.
AB  - BACKGROUND: The aim of this study was to investigate potential associations
      between gender equality at work and self-rated health. METHODS: 2861 employees in
      21 companies were invited to participate in a survey. The mean response rate was
      49.2%. The questionnaire contained 65 questions, mainly on gender equality and
      health. Two logistic regression analyses were conducted to assess associations
      between (i) self-rated health and a register-based company gender equality index
      (OGGI), and (ii) self-rated health and self-rated gender equality at work.
      RESULTS: Even though no association was found between the OGGI and health, women
      who rated their company as "completely equal" or "quite equal" had higher odds of
      reporting "good health" compared to women who perceived their company as "not
      equal" (OR = 2.8, 95% confidence interval = 1.4 - 5.5 and OR = 2.73, 95% CI = 1.6
      4.6). Although not statistically significant, we observed the same trends in men.
      The results were adjusted for age, highest education level, income, full or part
      time employment, and type of company based on the OGGI. CONCLUSIONS: No
      association was found between gender equality in companies, measured by register
      based index (OGGI), and health. However, perceived gender equality at work
      positively affected women's self-rated health but not men's. Further
      investigations are necessary to determine whether the results are fully credible
      given the contemporary health patterns and positions in the labour market of
      women and men or whether the results are driven by selection patterns.

PMID- 22985389
TI  - Roles of Arg427 and Arg472 in the binding and allosteric effects of acetyl CoA in
      pyruvate carboxylase.
AB  - Mutation of Arg427 and Arg472 in Rhizobium etli pyruvate carboxylase to serine or
      lysine greatly increased the activation constant (K(a)) of acetyl CoA, with the
      increase being greater for the Arg472 mutants. These results indicate that while
      both these residues are involved in the binding of acetyl CoA to the enzyme,
      Arg472 is more important than Arg427. The mutations had substantially smaller
      effects on the k(cat) for pyruvate carboxylation. Part of the effects of the
      mutations was to increase the K(m) for MgATP and the K(a) for activation by free
      Mg(2+) determined at saturating acetyl CoA concentrations. The inhibitory effects
      of the mutations on the rates of the enzyme-catalyzed bicarbonate-dependent ATP
      cleavage, carboxylation of biotin, and phosphorylation of ADP by carbamoyl
      phosphate indicate that the major locus of the effects of the mutations was in
      the biotin carboxylase (BC) domain active site. Even though both Arg427 and
      Arg472 are distant from the BC domain active site, it is proposed that their
      contacts with other residues in the allosteric domain, either directly or through
      acetyl CoA, affect the positioning and orientation of the biotin-carboxyl carrier
      protein (BCCP) domain and thus the binding of biotin at the BC domain active
      site. On the basis of the kinetic analysis proposed here, it is proposed that
      mutations of Arg427 and Arg472 perturb these contacts and consequently the
      binding of biotin at the BC domain active site. Inhibition of pyruvate
      carboxylation by the allosteric inhibitor l-aspartate was largely unaffected by
      the mutation of either Arg427 or Arg472.

PMID- 22985390
TI  - Gallstones in New Zealand: composition, risk factors and ethnic differences.
AB  - BACKGROUND: Gallstone disease is a worldwide problem causing morbidity, mortality
      and a drain on health-care resources. This prospective study aimed to investigate
      the spectrum of gallstone types in New Zealand and relate these to known risk
      factors. METHODS: Gallstone samples were collected from 107 patients undergoing
      surgery for gallstone disease at Auckland City Hospital between June 2009 and
      June 2010. Detailed chemical analyses were performed using Fourier Transform
      Raman spectroscopy. The relationship between gallstone type and age, gender,
      ethnicity, obesity and positive family history were analysed. RESULTS: Median age
      was 51 years (range 19-88), 75 (70%) were female, one third were obese (body mass
      index >= 30) and 41% had a positive family history. Major ethnic groups were
      European (51%), Asian (23%) and Maori/Pacific (18%). Gallstone types included
      pure or mixed cholesterol stones (74%), black pigment stones (20%) and brown
      pigment stones (5%). Asians had a higher proportion of black pigment stones and
      NZ Europeans had more cholesterol and mixed cholesterol stones (odds ratio 3.6
      (95% CI 1.1 to 11.5)). The frequency of cholesterol/mixed cholesterol stones was
      not significantly different between NZ Europeans and Maori/Pacific groups (P =
      0.7). Black pigment stones were more common in older patients (mean 68.0 years
      compared with 47.6 for cholesterol/mixed cholesterol stones) (P = 0.0001). There
      was no significant relationship between stone type and family history (P = 0.16)
      or gender (P = 0.17). CONCLUSION: This novel prospective study highlights risk
      factors and ethnic differences in gallstone composition in New Zealand. These may
      be important when considering gallstone prevention strategies.

PMID- 22985391
TI  - The effects of lidocaine used in sciatic nerve on the pharmacodynamics and
      pharmacokinetics of ropivacaine in sciatic nerve combined with lumbar plexus
      blockade: a double-blind, randomized study.
AB  - In this controlled, randomized, double-blind study, we compared the
      pharmacodynamics and pharmacokinetics of ropivacaine and staged injection of
      lidocaine and ropivacaine in a combined lumbar plexus-sciatic nerve block. The
      experiment was performed in two parts: pharmacodynamics study (Group r, n = 20;
      Group lr, n = 20) and pharmacokinetics study (Group R, n = 10; Group LR, n = 10).
      The sciatic nerve blockade was performed using either (1) 10 mL of 2% lidocaine
      and then 10 mL of 0.75% ropivacaine (Group lr and Group LR) or (2) 10 mL of
      normal saline (N.S.) and then 10 mL of 0.75% ropivacaine (Group r and Group R).
      Two kinds of solutions were 'staged' injection. The sensory onset time and
      sensory recovery time were assessed in the pharmacodynamics study. Arterial blood
      samples were collected for the pharmacokinetics study. Sciatic sensory block
      onset times were reduced, and the sensory recovery times were decreased in Group
      lr. C(max) of ropivacaine in Group LR was significantly higher than that in Group
      R. A significant increase in AUC((0-t)) and AUC((0-infinity)) was observed in
      Group LR compared with Group R. When 2% lidocaine and 0.75% ropivacaine are used
      for a combined sciatic nerve-lumbar plexus block by 'staged' injection, lidocaine
      induced faster onset times, decreased the block duration and increased the AUC
      and C(max) of ropivacaine.

PMID- 22985392
TI  - Regiochemical effects of furan substitution on the electronic properties and
      solid-state structure of partial fused-ring oligothiophenes.
AB  - Oligomers containing the new fused-ring heterocyclic conjugated building block
      thieno[3,2-b]furan were synthesized, and the effects associated with furan ring
      substitution into fused-ring oligothiophenes on the electronic properties and
      solid-state structure were assessed. A series of four-ring oligomers which vary
      in the degree of furan ring substitution and the regiochemistry of placement were
      synthesized via Stille cross-coupling and oxidative homocoupling strategies. The
      electronic properties of these oligomers were studied by UV-vis absorption and
      fluorescence spectroscopies. Substitution of furan rings at the terminal
      positions yields oligomers with a narrower HOMO-LUMO gap relative to the all
      thiophene analogue 2,2'-bithieno[3,2-b]thiophene, and incorporation of furan
      rings at the interior positions results in oligomers with an increase in rigidity
      and a higher fluorescence quantum yield. Packing motifs of the oligomers were
      determined using single crystal X-ray diffraction. In contrast to the herringbone
      crystal packing observed for nonfused oligothiophenes, oligofurans, thiophene
      furan hybrid oligomers, and the all-thiophene analogue 2,2'-bithieno[3,2
      b]thiophene, all three regioisomers derived from the dimerization of thieno[3,2
      b]furan arrange in a pi-stacked packing motif in the solid state.

PMID- 22985393
TI  - Direct, redox-neutral prenylation and geranylation of secondary carbinol C-H
      bonds: C4-regioselectivity in ruthenium-catalyzed C-C couplings of dienes to
      alpha-hydroxy esters.
AB  - The ruthenium catalyst generated in situ from Ru(3)(CO)(12) and
      tricyclohexylphosphine, PCy(3), promotes the redox-neutral C-C coupling of aryl
      substituted alpha-hydroxy esters to isoprene and myrcene at the diene C4
      position, resulting in direct carbinol C-H prenylation and geranylation,
      respectively. This process enables direct conversion of secondary to tertiary
      alcohols in the absence of stoichiometric byproducts or premetalated reagents,
      and is the first example of C4-regioselectivity in catalytic C-C couplings of 2
      substituted dienes to carbonyl partners. Mechanistic studies corroborate a
      catalytic cycle involving diene-carbonyl oxidative coupling.

PMID- 22985394
TI  - Efficacy of applying self-assessment of larviciding operation, Chabahar, Iran.
AB  - BACKGROUND: Appropriate supervision, along with availability of an effective
      system for monitoring and evaluation, is a crucial requirement to guarantee
      sufficient coverage and quality of malaria vector control procedures. This study
      evaluated the efficacy of self-assessment practice as a possible innovative
      method towards achieving high coverage and excellent quality of larviciding
      operation in Iran. METHODS: The research was conducted on the randomly selected
      rural health centre of Kanmbel Soliman with 10 staff and 30 villages, in three
      main steps: (i) assessment of effectiveness of larviciding operations in the
      study areas before intervention through external assessment by a research team;
      (ii) self-assessment of larviciding operations (intervention) by staff every
      quarter for three rounds; and, (iii) determining the effectiveness of applying
      self-assessment of larviciding operations in the study areas. Two toolkits were
      used for self-assessment and external evaluation. The impact of self-assessment
      of larviciding operations was measured by two indicators: percentage of missed
      breeding habitats and cleaned breeding habitats among randomly selected breeding
      sites. Moreover, the correlation coefficients were measured between self
      assessment measures and scores from external evaluation. The correlation
      coefficient and Mann Whitney test were used to analyse data. RESULTS: Following
      the utilization of self-assessment, the percentage of missed breeding habitats
      decreased significantly from 14.23% to 1.91% (P <0.001). Additionally, the
      percentage of cleaned breeding habitats among randomly selected breeding sites
      increased from 66.89% to 95.28% (P <0.001). The external evaluation also showed
      significant effects of self-assessment in performance of vector control; the
      maximum effect of intervention were seen in an action plan for monitoring and
      evaluation of larviciding operations at field level, geographical reconnaissance
      for the registration of breeding habitats and worker skills related to
      larviciding.Before intervention, the results of self-assessment practice were
      compatible with external evaluation in 76.3% of 139 reviewed reports of self
      assessment. After intervention, the findings of self-assessment and external
      evaluation were similar in the vast majority of reviewed reports (95%).
      CONCLUSION: The self-assessment tool seems to be valid and reliable in improving
      effectiveness of larviciding operations. Furthermore, the result of self
      assessment is more compatible with external evaluation results if it would be
      applied frequently. Therefore, it can be used as an alternative assessment
      technique in the evaluation of larviciding operations in addition to traditional
      assessment methods.

PMID- 22985395
TI  - Circadian egg production by Echinostoma caproni (Digenea: Echinostomatidae) in
      ICR mice.
AB  - Circadian egg production by Echinostoma caproni was investigated in ICR mice.
      Four female mice were infected with 25 E. caproni metacercariae, maintained in
      individual cages on a 12:12 light:dark cycle, and provided food and water ad
      libitum. Twenty-eight, 51, and 58 days post-infection, mice were transferred to
      individual, wire-bottomed cages and feces were collected every 2 hr for 24 hr.
      The feces were weighed and processed immediately to estimate the number of eggs
      present. Fecal output and egg production were standardized to unit maxima for
      analysis. Standardized egg count and standardized fecal output followed
      distinctly circadian patterns and covaried. Egg production was highest from 2200
      to 0200 hr and lowest from 1000 to 1800 hr. These correspond to the highest and
      lowest fecal production, and highest and lowest periods of host activity,
      respectively. Egg density (eggs/g of feces) covaried weakly with fecal output
      with an additional peak at 0800-1000 hr, suggesting E. caproni is responding to
      changes in host physiology in timing of the production and release of eggs into
      the intestine. The continuous production and release of eggs during the patent
      period, coupled with the circadian pattern of daily egg release by E. caproni ,
      would result in the widest dispersal of eggs in the host environment and enhance
      transmission to the first intermediate host.

PMID- 22985396
TI  - Redox reactions of reduced flavin mononucleotide (FMN), riboflavin (RBF), and
      anthraquinone-2,6-disulfonate (AQDS) with ferrihydrite and lepidocrocite.
AB  - Flavins are secreted by the dissimilatory iron-reducing bacterium Shewanella and
      can function as endogenous electron transfer mediators. To assess the potential
      importance of flavins in Fe(III) bioreduction, we investigated the redox reaction
      kinetics of reduced flavin mononucleotide (i.e., FMNH(2)) and reduced riboflavin
      (i.e., RBFH(2)) with ferrihydrite and lepidocrocite. The organic reductants
      rapidly reduced and dissolved ferrihydrite and lepidocrocite in the pH range 4-8.
      The rate constant k for 2-line ferrihydrite reductive dissolution by FMNH(2) was
      87.5 +/- 3.5 M(-1).s(-1) at pH 7.0 in batch reactors, and k was similar for
      RBFH(2). For lepidocrocite, k was 500 +/- 61 M(-1).s(-1) for FMNH(2) and 236 +/-
      22 M(-1).s(-1) for RBFH(2). The surface area normalized initial reaction rates
      (r(a)) were between 0.08 and 77 MUmol.m(-2).s(-1) for various conditions in
      stopped-flow experiments. Initial rates (r(o)) were first-order with respect to
      iron(III) oxide concentration, and r(a) increased with decreasing pH. Poorly
      crystalline 2-line ferrihydrite yielded the highest r(a), followed by more
      crystalline 6-line ferrihydrite and crystalline lepidocrocite. Compared to a
      previous whole-cell study with Shewanella oneidensis strain MR-1, our findings
      suggest that the reduction of electron transfer mediators by the Mtr (i.e., metal
      reducing) pathway coupled to lactate oxidation is rate limiting, rather than
      heterogeneous electron transfer to the iron(III) oxide.

PMID- 22985397
TI  - Anti-inflammatory effects of naringin in chronic pulmonary neutrophilic
      inflammation in cigarette smoke-exposed rats.
AB  - Naringin, a well-known flavanone glycoside of grapefruit and citrus fruits, was
      found to be as an effective anti-inflammatory compound in our previous
      lipopolysaccharide-induced acute lung injury mouse model via blockading activity
      of nuclear factor kappaB. The current study sought to explore the anti
      inflammatory effects of naringin on chronic pulmonary neutrophilic inflammation
      in cigarette smoke (CS)-induced rats. Seventy Sprague-Dawley rats were randomly
      divided into seven groups to study the effects of CS with or without various
      concentrations of naringin or saline for 8 weeks. The results revealed that
      naringin supplementation at 20, 40, and 80 mg/kg significantly increased body
      weight of CS-induced rats as compared to that in the CS group. Moreover, naringin
      of 20, 40, and 80 mg/kg prevented CS-induced infiltration of neutrophils and
      activation of myeloperoxidase and matrix metalloproteinase-9, in parallel with
      suppression of the release of cytokines, such as tumor necrosis factor-alpha and
      interleukin-8 (IL-8). IL-10 in bronchoalveolar lavage fluid was significantly
      suppressed after CS exposure, but dose dependently elevated by naringin. The
      results from hematoxylin and eosin staining revealed that naringin dose
      dependently reduced CS-induced infiltration of inflammatory cells, thickening of
      the bronchial wall, and expansion of average alveolar airspace. In conclusion,
      our data suggest that naringin is an effective anti-inflammatory compound for
      attenuating chronic pulmonary neutrophilic inflammation in CS-induced rats.

PMID- 22985398
TI  - Effect of Rosemarinus officinalis L. on MMP-9, MCP-1 levels, and cell migration
      in RAW 264.7 and smooth muscle cells.
AB  - Atherosclerosis is a chronic and progressive inflammatory disease. Novel anti
      inflammatory therapies may have promise as treatment strategies for
      cardiovascular risk reduction. Rosemary (Rosemarinus officinalis L.) has been
      used in folk medicine to treat headaches, epilepsy, poor circulation, and many
      other ailments. It was found that rosemary could act as a stimulant and mild
      analgesic and could reduce inflammation. However, the mechanisms underlying the
      anti-inflammatory and antiatherosclerotic effects of rosemary need more study.
      This study investigated effects of the rosemary components, carnosic acid (CA),
      and carnosol (CAR), on cell migration. Monocyte chemoattractant protein-1 (MCP-1)
      and matrix metalloproteinase-9 (MMP-9) were determined by Western blot and
      gelatin zymography, respectively, in RAW 264.7 macrophages and vascular smooth
      muscle cells (VSMCs). VSMC migration was assessed by a Matrigel migration assay.
      Active compounds of rosemary extracts were also analyzed using a reversed-phase
      high-performance liquid chromatography. MMP-9 and MCP-1 activities were markedly
      diminished with methanol extract (RM), n-hexane fraction (RH), and CA in RAW
      264.7 cells. RM, RH, CA, and CAR suppressed tumor necrosis factor-alpha-induced
      VSMC migration by inhibiting MMP-9 expression. Chromatograms of RM- and RH
      containing CA and CAR revealed higher CA contents of RM (9.4%, 93.85 MUg/mg dry
      wt.) and, especially, RH (18.4%, 184.00 MUg/mg dry wt.), which were appreciably
      elevated compared with the similar CAR content in RM and RH (3.7%, 37.30 MUg/mg
      dry wt.; and 2.5%, 25.05 MUg/mg dry wt., respectively). Rosemary, especially its
      CA component, has potential antiatherosclerosis effects related to cell
      migration.

PMID- 22985399
TI  - Polysaccharide isolated from Angelica sinensis inhibits hepcidin expression in
      rats with iron deficiency anemia.
AB  - A novel polysaccharide named Angelica sinensis polysaccharide (ASP) was obtained
      from the powdered and defatted roots of A. sinensis (Oliv.) Diels. The molecular
      weight of ASP was determined to be 78 kDa and was 95.0% sugars consisting of
      mostly arabinose, glucose, and galactose with a molar ratio of 1:5.68:3.91. A
      previous study indicated that ASP may increase plasma iron levels by suppressing
      the expression of hepcidin, a negative regulator of body iron metabolism, in the
      liver. The present study aims to clarify the inhibitory effect of ASP on hepcidin
      expression in rat models of iron deficiency anemia (IDA), and clarify the
      mechanisms involved. It was demonstrated that ASP significantly reduced hepcidin
      expression by inhibiting the expression of mothers against decapentaplegic
      protein 4 (SMAD4) in liver and stimulating the secretion of erythropoietin, which
      further downregulated hepcidin by repressing CCAAT/enhancer-binding protein alpha
      (C/EBPalpha) and the phosphorylation of signal transducer and activator of
      transcription 3/5. The results indicate that ASP can suppress the expression of
      hepcidin in rats with IDA, and may be useful for the treatment of IDA.

PMID- 22985401
TI  - Highly stable concentrated nanoemulsions by the phase inversion composition
      method at elevated temperature.
AB  - Oil-in-water nanoemulsions were produced in the system water/Span 80-Tween
      80/paraffin oil via the phase inversion composition (PIC) method at elevated
      temperature. With the increase of preparation temperature from 20 to 70  degrees
      C, we found that the emulsion droplet diameter decreases from 10.3 MUm to 51 nm,
      proving the formation of nanoemulsions. The viscosity of nanoemulsions clearly
      increases with droplet volume fraction, phi, but the droplet size changes less.
      Significantly, at phi <= 0.5, the size distribution of nanoemulsions can be kept
      unchangeable more than 5 months. These results proved that the highly viscous
      paraffin oil can hardly be dispersed by the PIC method at 25  degrees C, but the
      increase in preparation temperature makes it possible for producing monodisperse
      nanoemulsions. Once the nanoemulsion is produced, the stability against Ostwald
      ripening is outstanding due to the extremely low solubility of the paraffin oil
      in the continuous phase. The highly stable nanoemulsions are of great importance
      in practical applications.

PMID- 22985400
TI  - Spectroscopic and DFT studies of second-sphere variants of the type 1 copper site
      in azurin: covalent and nonlocal electrostatic contributions to reduction
      potentials.
AB  - The reduction potentials (E(0)) of type 1 (T1) or blue copper (BC) sites in
      proteins and enzymes with identical first coordination spheres around the redox
      active copper ion can vary by ~400 mV. Here, we use a combination of low
      temperature electronic absorption and magnetic circular dichroism, electron
      paramagnetic resonance, resonance Raman, and S K-edge X-ray absorption
      spectroscopies to investigate a series of second-sphere variants--F114P, N47S,
      and F114N in Pseudomonas aeruginosa azurin--which modulate hydrogen bonding to
      and protein-derived dipoles nearby the Cu-S(Cys) bond. Density functional theory
      calculations correlated to the experimental data allow for the fractionation of
      the contributions to tuning E(0) into covalent and nonlocal electrostatic
      components. These are found to be significant, comparable in magnitude, and
      additive for active H-bonds, while passive H-bonds are mostly nonlocal
      electrostatic in nature. For dipoles, these terms can be additive to or oppose
      one another. This study provides a methodology for uncoupling covalency from
      nonlocal electrostatics, which, when coupled to X-ray crystallographic data,
      distinguishes specific local interactions from more long-range protein/active
      interactions, while affording further insight into the second-sphere mechanisms
      available to the protein to tune the E(0) of electron-transfer sites in biology.

PMID- 22985402
TI  - Glycosylations of cyclopropyl-modified carbohydrates: remarkable beta-selectivity
      using a mannose building block.
AB  - A mannosyl donor bearing a spiroannulated cyclopropane unit at C-5 has been
      prepared, and its behavior in glycosylation reactions investigated. Selectivities
      in favor of the beta-anomer were observed. Corresponding di- and trisaccharides
      incorporating the rigid cyclopropane motif were assembled.

PMID- 22985403
TI  - Central centrifugal cicatricial alopecia severity is associated with cowhage
      induced itch.
AB  - BACKGROUND: Patients with central centrifugal cicatricial alopecia (CCCA) often
      suffer from varying degrees of itch, pain and burning sensations. However, the
      neural component of these skin sensations has not been assessed. OBJECTIVE: To
      conduct a comprehensive analysis of C nerve fibre function relating to itch and
      pain perception in patients with CCCA using thermosensory testing and
      experimental itch models. METHODS: Fifteen healthy African-American women and 16
      African-American female patients with CCCA participated in the study and
      underwent quantitative computerized thermosensory testing to assess warmth and
      heat pain thresholds. Itch was induced using histamine iontophoresis and
      application of cowhage spicules, and the intensity of each itch was assessed. The
      association between itch intensity and CCCA severity score was examined. RESULTS:
      A positive correlation between CCCA severity score and peak itch ratings of
      cowhage on the lesional scalp (crown) was observed (P = 0.023, r = 0.562).
      Notably, the histamine peak itch rating was not found to have a significant
      correlation with CCCA severity score (P = 0.913). The crown also had
      significantly higher warmth and pain thresholds than the occiput in both healthy
      subjects and patients with CCCA. CONCLUSIONS: Our results suggest a putative role
      for the protease-activated receptor (PAR)-2, which is activated by cowhage, in
      the pathogenesis of CCCA. Future studies should examine PAR-2-directed
      therapeutics for patients with CCCA. Examining for itch and other dysaesthesias
      in patients with CCCA is of vital importance to dermatologists in assessing
      disease severity.

PMID- 22985404
TI  - Spin accumulation assisted by the Aharonov-Bohm-Fano effect of quantum dot
      structures.
AB  - : We investigate the spin accumulations of Aharonov-Bohm interferometers with
      embedded quantum dots by considering spin bias in the leads. It is found that
      regardless of the interferometer configurations, the spin accumulations are
      closely determined by their quantum interference features. This is mainly
      manifested in the dependence of spin accumulations on the threaded magnetic flux
      and the nonresonant transmission process. Namely, the Aharonov-Bohm-Fano effect
      is a necessary condition to achieve the spin accumulation in the quantum dot of
      the resonant channel. Further analysis showed that in the double-dot
      interferometer, the spin accumulation can be detailedly manipulated. The spin
      accumulation properties of such structures offer a new scheme of spin
      manipulation. When the intradot Coulomb interactions are taken into account, we
      find that the electron interactions are advantageous to the spin accumulation in
      the resonant channel.

PMID- 22985405
TI  - Cold stratification and exogenous nitrates entail similar functional proteome
      adjustments during Arabidopsis seed dormancy release.
AB  - Despite having very similar initial pools of stored mRNAs and proteins in the dry
      state, mature Arabidopsis seeds can either proceed toward radicle protrusion or
      stay in a dormant state upon imbibition. Dormancy breaking, a prerequisite to
      germination completion, can be induced by different treatments though the
      underlying mechanisms remain elusive. Thus, we investigated the consequence of
      such treatments on the seed proteome. Two unrelated dormancy-releasing treatments
      were applied to dormant seeds, namely, cold stratification and exogenous
      nitrates, in combination with differential proteomic tools to highlight the
      specificities of the imbibed dormant state. The results reveal that both
      treatments lead to highly similar proteome adjustments. In the imbibed dormant
      state, enzymes involved in reserve mobilization are less accumulated and it
      appears that several energetically costly processes associated to seed
      germination and preparation for subsequent seedling establishment are repressed.
      Our data suggest that dormancy maintenance is associated to an abscisic-acid
      dependent recapitulation of the late maturation program resulting in a higher
      potential to cope with environmental stresses. The comparison of the present
      results with previously published -omic data sets reinforces and extends the
      assumption that post-transcriptional, translational, and post-translational
      regulations are determinant for seed germination.

PMID- 22985406
TI  - What issues matter most to people with multiple myeloma and how well are we
      measuring them? A systematic review of quality of life tools.
AB  - INTRODUCTION: Treatment advances in multiple myeloma have increased expected
      survival from months to years for some patients. Alongside improved survival
      emerges a need to better understand and measure health-related quality of life
      (HRQOL), both in research and clinical settings. OBJECTIVES: (i) Identify HRQOL
      tools validated for use in myeloma; (ii) identify issues important to HRQOL from
      the point of view of patients with myeloma; (iii) describe the measurement
      properties of each HRQOL tool; (iv) evaluate the content validity of HRQOL tools
      in terms of their ability to capture all issues important to patients and (v)
      explore the suitability of each HRQOL tool for use in different settings. METHOD:
      Systematic literature review of six databases with no limits by date or language.
      RESULTS: Thirty-nine studies reported validation of 13 HRQOL instruments. Seven
      studies identified issues important to HRQOL from the patients' perspective. No
      instrument was comprehensive to all issues important to patients. The EORTC-QLQ
      C30 and MY24 have undergone the most comprehensive psychometric validation. Most
      validation occurred in trial patients and not clinically representative groups.
      No studies evaluated clinical utility of tools alongside routine practice.
      CONCLUSION: The best existing HRQOL tools are designed predominantly for use in
      research. Reliable, valid and responsive tools exist for this purpose, but may
      miss issues important to patients. The design of HRQOL measures should be guided
      by intended utility, whether for research or clinical practice, and further
      validation of HRQOL tools in clinically representative groups is needed.
      Development and validation of HRQOL tools for clinical use may be of value.

PMID- 22985407
TI  - A cross-sectional analysis of how young adults perceive tobacco brands:
      implications for FCTC signatories.
AB  - BACKGROUND: The Framework Convention on Tobacco Control calls for the elimination
      of tobacco advertising, promotion and sponsorship. To test whether tobacco
      packaging functions as advertising by communicating attractive and distinctive
      brand attributes, we explored how young adult smokers and non-smokers interpreted
      familiar and unfamiliar tobacco brands. METHODS: We conducted an on-line survey
      of 1035 young adult smokers and non-smokers aged 18-30. Participants evaluated
      eight tobacco brands using ten attributes based on brand personality scales. We
      used factor analysis and ANOVA to examine patterns in brand-attribute
      associations. RESULTS: Young adults distinguished between brands on the basis of
      their packaging alone, associated each brand with specific attributes, and were
      equally able to interpret familiar and unfamiliar brands. Contrary to our
      expectations, non-smokers made more favourable brand-attribute associations than
      smokers, but both groups described Basic, a near generic brand, as 'plain' or
      'budget'. There were no significant gender or ethnicity differences. CONCLUSIONS:
      Tobacco packaging uses logos, colours and imagery to create desirable
      connotations that promote and reinforce smoking. By functioning in the same way
      as advertising, on-pack branding breaches Article 13 of the FCTC and refutes
      tobacco companies' claims that pack livery serves only as an indentifying device
      that simplifies smokers' decision-making. Given this evidence, signatories should
      see plain packaging policies as a priority consistent with their FCTC obligations
      to eliminate all tobacco advertising and promotion.

PMID- 22985408
TI  - Assessing bias against overweight individuals among nursing and psychology
      students: an implicit association test.
AB  - AIM AND OBJECTIVES: To determine the implicit or unconscious attitudes of Nursing
      and Psychology majors towards overweight individuals in medical and non-medical
      contexts. BACKGROUND: Obesity is a leading health concern today, which impacts
      both physical and psychological health. Overweight individuals confront social
      biases in many aspects of their lives including health care. Examining the views
      of Nursing and Psychology students may reveal implicit attitudes towards
      overweight individuals that may lead to prejudiced behaviours. DESIGN: A mixed
      design experiment with one between-subjects variable (student major: Nursing or
      Psychology) and one within-subjects variable (condition: congruent or
      incongruent) was used to assess implicit attitudes in two convenience samples of
      Nursing and Psychology students. METHODS: A computerised implicit association
      test was used to determine implicit attitudes towards overweight individuals in
      medical and non-medical contexts. A total of 90 students from Nursing (n= 45) and
      Psychology (n = 45) were recruited to complete an implicit association test.
      Reaction times in milliseconds between the congruent trials (stereotype
      consistent) and incongruent trials (stereotype inconsistent) were compared with
      determine adherence to social stereotypes or weight bias. RESULTS: A
      statistically significant implicit bias towards overweight individuals was
      detected in both subject groups and in both target settings (medical vs. non
      medical). Stronger weight bias was found when the stimulus targets were female
      than male. CONCLUSIONS: Findings from this study expand understanding of the
      implicit attitudes and social biases of Nursing and Psychology students. The
      views held by these future healthcare professionals may negatively impact patient
      care. RELEVANCE TO CLINICAL PRACTICE: Providing education and support to
      overweight individuals is central to Nursing practice in a society struggling to
      manage obesity. Negative stereotypes or beliefs about these individuals may
      result in poor patient care. Therefore, nurses and other healthcare professionals
      must be aware of personal biases and work to develop methods to address weight
      related issues in a therapeutic manner.

PMID- 22985409
TI  - Analysis of malaria surveillance data in Ethiopia: what can be learned from the
      Integrated Disease Surveillance and Response System?
AB  - BACKGROUND: Routine malaria surveillance data is useful for assessing incidence
      and trends over time, and in stratification for targeting of malaria control. The
      reporting completeness and potential bias of such data needs assessment. METHODS:
      Data on 17 malaria indicators were extracted from the Integrated Disease
      Surveillance and Response System database for July 2004 to June 2009 (Ethiopian
      calendar reporting years 1997 to 2001). Reporting units were standardized over
      time with 2007 census populations. The data were analysed to show reporting
      completeness, variation in risk by reporting unit, and incidence trends for
      malaria indicators. RESULTS: Reporting completeness, estimated as product of unit
      month and health facility reporting, was over 80% until 2009, when it fell to 56%
      during a period of reorganization in the Ministry of Health. Nationally the
      average estimated annual incidence of reported total malaria for the calendar
      years 2005 to 2008 was 23.4 per 1000 persons, and of confirmed malaria was 7.6
      per 1,000, with no clear decline in out-patient cases over the time period.
      Reported malaria in-patient admissions and deaths (averaging 6.4 per 10,000 and
      2.3 per 100,000 per year respectively) declined threefold between 2005 and 2009,
      as did admissions and deaths reported as malaria with severe anaemia. Only 8 of
      86 reporting units had average annual estimated incidence of confirmed malaria
      above 20 per 1,000 persons, while 26 units were consistently below five reported
      cases per 1,000 persons per year. CONCLUSION: The Integrated Disease Surveillance
      and Response System functioned well over the time period mid 2004 to the end of
      2008. The data suggest that the scale up of interventions has had considerable
      impact on malaria in-patient cases and mortality, as reported from health centres
      and hospitals. These trends must be regarded as relative (over space and time)
      rather than absolute. The data can be used to stratify areas for improved
      targeting of control efforts to steadily reduce incidence. They also provide a
      baseline of incidence estimates against which to gauge future progress towards
      elimination. Inclusion of climate information over this time period and extension
      of the dataset to more years is needed to clarify the impact of control measures
      compared to natural cycles on malaria.

PMID- 22985410
TI  - Recruitment of neural precursor cells from circumventricular organs of patients
      with cerebral ischaemia.
AB  - AIMS: Adult neurogenesis is well described in the subventricular zone of the
      lateral ventricle walls and in the subgranular zone of the hippocampal dentate
      gyrus. However, recent studies indicate that self-renewal of neural stem cells
      (NSCs) is not restricted to these niches, but that diverse areas of the adult
      brain are capable of generating new neurones and responding to various
      pathological alterations. In particular, NSCs have been identified in
      circumventricular organs (CVOs) of the adult mouse brain. METHODS: In order to
      detect possible neural stem or progenitor cells in CVOs of the human brain, we
      analysed post mortem human brain tissue from patients without neuropathological
      changes (n = 16) and brains from patients with ischaemic stroke (n = 16).
      RESULTS: In all analysed CVOs (area postrema, median eminence, pineal gland and
      neurohypophysis) we observed cells with expression of early NSC markers, such as
      GFAP, nestin, vimentin, OLIG2 and PSA-NCAM, with some of them coexpressing Ki67
      as a marker of cell proliferation. Importantly, stroke patients displayed an up
      to fivefold increase with respect to the relative number of Ki67- and OLIG2
      expressing cells within their CVOs. CONCLUSIONS: Our findings are compatible with
      a scenario where CVOs may serve as a further source of NSCs in the adult human
      brain and may contribute to neurogenesis and brain plasticity in the context of
      brain injury.

PMID- 22985411
TI  - Targeting the androgen receptor signalling axis in castration-resistant prostate
      cancer (CRPC).
AB  - What's known on the subject? and What does the study add? Castration resistance
      has been appreciated for decades, and several mechanisms theorising on this
      effect have been proposed. A rich pipeline of novel agents, including abiraterone
      and MDV3100, have provided proof of principle that novel agents targeting the AR
      signalling pathway with superior selectivity and activity than predecessors have
      yielded significant clinical benefit for patients with metastatic castration
      resistant prostate cancer. Our review provides an update in the development of
      several novel agents targeting the AR signalling pathway now in clinical testing,
      as well as review novel therapies in development with distinct mechanisms of
      action showing promising preclinical activity. * Despite undergoing local therapy
      with curative intent, 20-30% of patients with prostate cancer will ultimately
      development metastatic disease, leading to morbidity and mortality. * Androgen
      deprivation therapy (ADT) for men with metastatic prostate cancer results in
      transient clinical benefit, but ultimately, cancers progress despite castrate
      levels of serum testosterone, a clinical state classically referred to as
      'hormone refractory' disease. * In this review, we examine mechanisms of
      resistance to ADT that have redefined our understanding of the more appropriately
      termed 'castration resistant' disease, and have paved the way for a new
      generation of therapeutics targeting the androgen signalling axis in advanced
      prostate cancer.

PMID- 22985413
TI  - Matrix behavior during sample preparation using metabolomics analysis approach
      for pesticide residue analysis by GC-MS in agricultural products.
AB  - The detailed matrices and their behaviors during pesticide residue analyses were
      clarified using a metabolomics analysis approach. The matrix profile was
      investigated using two different extraction solvents, acetone and acetonitrile.
      Acetone extracted the matrix components with a wide range of log P(O/W) values.
      Components with log P(O/W) values >10, such as sterols and tocopherols, and
      components with log P(O/W) values <3.2 were more extracted by acetone than by
      acetonitrile. In contrast, components with log P(O/W) values in the range from
      3.2 to 10 were extracted by both acetone and acetonitrile at the same
      concentration level. The study also examined the difference in the column cleanup
      efficiency using a solid phase extraction (SPE). Florisil, silica gel, NH(2),
      PSA, and GCB were selected as representative columns for pesticide residue
      analysis, and acetone extraction of brown rice was selected in this experiment.
      Most of the matrix components were removed by either column, whereas
      monoacylglycerols, which are the components causing the matrix effect, were not
      removed by any column. Understanding such a detailed matrix behavior helps to
      develop a better analytical method for pesticide analysis using GC-MS.

PMID- 22985412
TI  - Cytochalasin D enhances the accumulation of a protease-resistant form of prion
      protein in ScN2a cells: involvement of PI3 kinase/Akt signalling pathway.
AB  - The conversion of a host-encoded PrPsen (protease-sensitive cellular prion
      protein) into a PrPres (protease-resistant pathogenic form) is a key process in
      the pathogenesis of prion diseases, but the intracellular mechanisms underlying
      PrPres amplification in prion-infected cells remain elusive. To assess the role
      of cytoskeletal proteins in the regulation of PrPres amplification, the effects
      of cytoskeletal disruptors on PrPres accumulation in ScN2a cells that were
      persistently infected with the scrapie Chandler strain have been examined. Actin
      microfilament disruption with cytochalasin D enhanced PrPres accumulation in
      ScN2a cells. In contrast, the microtubule-disrupting agents, colchicine,
      nocodazole and paclitaxel, had no effect on PrPres accumulation. In addition, a
      PI3K (phosphoinositide 3-kinase) inhibitor, wortmannin and an Akt kinase
      inhibitor prevented the cytochalasin D-induced enhancement of PrPres
      accumulation. Cytochalasin D-induced extension of neurite-like processes might
      correlate with enhanced accumulation of PrPres. The results suggest that the
      actin cytoskeleton and PI3K/Akt pathway are involved in the regulation of PrPres
      accumulation in prion-infected cells.

PMID- 22985414
TI  - Topography-specific spindle frequency changes in obstructive sleep apnea.
AB  - BACKGROUND: Sleep spindles, as detected on scalp electroencephalography (EEG),
      are considered to be markers of thalamo-cortical network integrity. Since
      obstructive sleep apnea (OSA) is a known cause of brain dysfunction, the aim of
      this study was to investigate sleep spindle frequency distribution in OSA. Seven
      non-OSA subjects and 21 patients with OSA (11 mild and 10 moderate) were studied.
      A matching pursuit procedure was used for automatic detection of fast (>=13 Hz)
      and slow (<13 Hz) spindles obtained from 30 min samples of NREM sleep stage 2
      taken from initial, middle and final night thirds (sections I, II and III) of
      frontal, central and parietal scalp regions. RESULTS: Compared to non-OSA
      subjects, Moderate OSA patients had higher central and parietal slow spindle
      percentage (SSP) in all night sections studied, and higher frontal SSP in
      sections II and III. As the night progressed, there was a reduction in central
      and parietal SSP, while frontal SSP remained high. Frontal slow spindle
      percentage in night section III predicted OSA with good accuracy, with OSA
      likelihood increased by 12.1%for every SSP unit increase (OR 1.121, 95% CI 1.013
      1.239, p=0.027). CONCLUSIONS: These results are consistent with diffuse,
      predominantly frontal thalamo-cortical dysfunction during sleep in OSA, as more
      posterior brain regions appear to maintain some physiological spindle frequency
      modulation across the night. Displaying changes in an opposite direction to what
      is expected from the aging process itself, spindle frequency appears to be
      informative in OSA even with small sample sizes, and to represent a sensitive
      electrophysiological marker of brain dysfunction in OSA.

PMID- 22985416
TI  - Infrared thermographic comparison of temperature increases on the root surface
      during dowel space preparations using circular versus oval fiber dowel systems.
AB  - PURPOSE: The purpose was to evaluate temperature increases during dowel space
      preparations with oval and circular fiber dowel systems. MATERIALS AND METHODS:
      This study included 42 single-rooted human mandibular premolars. Roots were
      scanned with cone-beam computerized tomography (CBCT) to determine the ovoid root
      canal morphology. Root canals were treated with Ni-Ti rotary instruments and
      obturated. A second CBCT was taken to determine the thinnest dentin thickness of
      each root. Roots were randomly divided into two groups (n = 21) according to the
      fiber dowel system used: group 1, circular fiber dowel system (D.T. Light-Post);
      group 2, oval fiber dowel system (Ellipson Post). Dowel spaces were prepared
      using a circular fiber dowel drill and a diamond-coated ultrasonic tip with an
      oval section under water cooling until 9 mm dowel spaces were obtained.
      Temperature changes were recorded from the thinnest root surfaces using a FLIR
      E60 thermal imaging camera. RESULTS: Temperature increases were significantly
      greater with the circular fiber dowel system than with the oval fiber dowel
      system (p < 0.05). CONCLUSIONS: Although both dowel systems generated high
      temperature increases on root surfaces, the relatively lower temperature increase
      associated with the use of oval fiber dowels in ovoid canals makes it preferable
      to the use of circular fiber dowels.

PMID- 22985415
TI  - 7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by
      decapping scavenger (DcpS) enzymes and potently inhibits their activity.
AB  - Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap
      structure following 3' -> 5' mRNA decay. Some previous studies suggested that
      both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show
      that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and
      m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA
      decapping by the Dcp1/2 complex in the 5' -> 3' mRNA decay, are not degraded by
      recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas
      mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by
      DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are,
      demonstrating the importance of a triphosphate chain for DcpS hydrolytic
      activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their
      corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively),
      indicating an involvement of the second nucleoside for efficient DcpS-mediated
      digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high
      binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of
      m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor.
      Our data have important implications for the regulatory role of m(7)GDP in mRNA
      metabolic pathways due to its possible interactions with different cap-binding
      proteins, such as DcpS or eIF4E.

PMID- 22985417
TI  - Transfusion-related acute lung injury after intravenous immunoglobulin treatment
      in a lung transplant recipient.
AB  - Three weeks after single-lung transplantation for pulmonary fibrosis, a patient
      with high serum levels of de novo donor-specific antibodies received high-dose
      intravenous immunoglobulin (IVIG) infusion (scheduled dose: 2 g/kg on 2 days) to
      prevent antibody-mediated rejection. Within the first hours after completion of
      infusions, he experienced acute lung injury involving the transplanted lung.
      Given the clinical evolution and the absence of an alternative diagnosis,
      transfusion-related acute lung injury (TRALI) was diagnosed. The IVIG
      administered on each day was from the same batch. At day 110, because of an
      increase in the serum titers of donor-specific antibodies, IVIG therapy was
      reintroduced but from a different batch, with excellent clinical tolerance. The
      lung injury was explored biologically, but no mechanism was revealed. Given the
      increasing use of IVIG in solid-organ recipients, clinicians should be aware of
      possible TRALI after IVIG infusion.

PMID- 22985418
TI  - Electronic regioselectivity of diarylalkynes in cobalt-mediated Pauson-Khand
      reaction: an experimental and computational study with para- and meta-substituted
      diarylalkynes and norbornene.
AB  - Both steric and electronic factors of substituted alkynes are known to guide
      alpha/beta-cyclopentenone regioselectivity in the cobalt-mediated Pauson-Khand
      reaction (PKR). In synthetic applications of the PKR, the steric factors can
      often override or render possible electronic effects. This study examined alkyne
      dependent electronic regioselectivity of cyclopentenone formation in PKR with
      norbornene and sterically equivalent, but electronically unsymmetrical, meta- and
      para-substituted diarylethynyls to unveil the role of electronic effects alone.
      In agreement with the literature reports, EDG para-substituted aryls, to some
      extent, favored the cyclopentenone alpha-regioisomer, while the EWG-substituted
      aryls correspondingly preferred the beta-regioisomer. The cooperation of EGW and
      EDG in diaryl-substituted alkynes did not lead to any increased
      regioselectivities that could be expected by a "push-pull" effect. Both EWG and
      EDG meta-substituted aryls preferred the beta-regioisomer, which was demonstrated
      by 3,5-dimethoxy- and 3,5-bis(trifluoromethyl)-1-phenylethynyls that yielded
      1/1.6 and 1/2.0 alpha/beta-regioselectivities, respectively. Theoretically,
      inspection of Hammett values of alpha-alkyne carbons gave qualitatively
      satisfactory prediction for para-substituted aryls but correlated only weakly
      with meta-substituted effects. Computational investigations at the DFT level
      revealed a correlation between NBO charges and the regioselectivity. Overall, the
      results suggest that the polarity of an alkyne, also designated by the relative
      polarization of aryl alpha-carbons, dictates the regioselectivity in the absence
      of steric effects.

PMID- 22985419
TI  - Functional characterization of new allelic polymorphisms identified in the
      promoter region of the human MxA gene.
AB  - The Mx proteins are high-molecular-weight dynamin-like proteins whose expression
      depends strictly on type-I and type-III interferons (IFN). Some isoforms are able
      to inhibit the life cycle of one or several viruses and are thus components of
      innate immune response. The human MxA protein displays the broadest antiviral
      spectrum which makes it appear as a key antiviral effector of innate immunity.
      Allelic polymorphisms located in the MxA gene promoter can be expected to affect
      the magnitude of MxA mRNA transcription in response to IFNs and therefore to
      alter the severity of viral diseases in humans. Here, three single nucleotide
      polymorphism sites (-309, -101 and +20) were examined for their ability to alter
      MxA gene promoter-driven reporter expression. We show that, besides the
      previously reported role of -123A and -88T, the presence of -101G is equally
      important. Moreover, when a promoter construct carries these three critical
      nucleotides, a first additional positive effect is conferred by a C at position 
      309 and, in this latter case, a second additional effect is produced by a A at
      position +20. This finding is clinically useful to improve prediction of IFN
      responsiveness in patients not only with viral diseases for which type-I IFN
      therapy is used. 

PMID- 22985420
TI  - Factors related to post-operative metabolic acidosis following major abdominal
      surgery.
AB  - BACKGROUND: Metabolic acidosis is frequently observed in perioperative patients,
      especially those who undergo major surgery. The aim of this study was to evaluate
      the factors related to post-operative metabolic acidosis and to attempt to
      identify the clinical effect of metabolic acidosis following major abdominal
      surgery. METHODS: We included 172 patients admitted to a surgical intensive care
      unit (ICU) following major abdominal surgery. All cases were divided into either
      the acidosis or the normal group using immediate post-operative standard base
      excess (SBE). The following clinical data were retrospectively obtained from the
      chart and ICU database: basic clinical characteristics, operative data, type and
      volume of fluid infused during the operation, post-operative arterial blood gas
      analysis, lactate, and central venous oxygen saturation. RESULTS: The predominant
      intraoperative fluid was either 0.9% saline or lactated Ringer's solution. The
      operation length, estimated blood loss, total fluid infused, total saline
      infused, lactate and corrected chloride were significantly higher in the acidosis
      group; however, central venous oxygen saturation was lower in the normal group.
      Among these factors, total infused saline and lactate level were independent
      factors related to metabolic acidosis. The comparison between the types of fluid
      revealed that the saline group had a significantly lower SBE, strong ion
      difference and higher corrected chloride. SBE was significantly correlated with
      lactate and total infused saline. ICU and hospital length of stay were
      significantly longer in the acidosis group. CONCLUSIONS: Post-operative metabolic
      acidosis following major abdominal surgery was closely related to both
      hyperchloremic acidosis associated with large saline infusion and lactic acidosis
      caused by lactataemia.

PMID- 22985421
TI  - Response to: Cost-effectiveness of using an extensively hydrolysed formula
      compared to an amino acid formula as first-line treatment for cow milk allergy in
      the UK.

PMID- 22985422
TI  - Efficient charge transport in semisynthetic zinc chlorin dye assemblies.
AB  - We have studied the charge transport properties of self-assembled structures of
      semisynthetic zinc chlorins (ZnChls) in the solid state by pulsed radiolysis time
      resolved microwave conductivity measurements. These materials can form either a
      two-dimensional (2D) brickwork-type slipped stack arrangement or a one
      dimensional (1D) tubular assemblies, depending on the exact molecular structure
      of the ZnChls. We have observed efficient charge transport with mobilities as
      high as 0.07 cm(2) V(-1) s(-1) for tubular assemblies of 3(1)-hydroxy ZnChls and
      up to 0.28 cm(2) V(-1) s(-1) for 2D stacked assemblies of 3(1)-methoxy ZnChls at
      room temperature. The efficient charge transporting capabilities of these
      organized assemblies opens the way to supramolecular electronics based on
      biological systems.

PMID- 22985423
TI  - Complement is dispensable for neurodegeneration in Niemann-Pick disease type C.
AB  - BACKGROUND: The immune system has been implicated in neurodegeneration during
      development and disease. In various studies, the absence of complement (that is,
      C1q deficiency) impeded the elimination of apoptotic neurons, allowing survival.
      In the genetic lysosomal storage disease Niemann-Pick C (NPC), caused by loss of
      NPC1 function, the expression of complement system components, C1q especially, is
      elevated in degenerating brain regions of Npc1-/- mice. Here we test whether
      complement is mediating neurodegeneration in NPC disease. FINDINGS: In normal
      mature mice, C1q mRNA was found in neurons, particularly cerebellar Purkinje
      neurons (PNs). In Npc1-/- mice, C1q mRNA was additionally found in activated
      microglia, which accumulate during disease progression and PN loss.
      Interestingly, C1q was not enriched on or near degenerating neurons. Instead, C1q
      was concentrated in other brain regions, where it partially co-localized with a
      potential C1q inhibitor, chondroitin sulfate proteoglycan (CSPG). Genetic
      deletion of C1q, or of the downstream complement pathway component C3, did not
      significantly alter patterned neuron loss or disease progression. Deletion of
      other immune response factors, a Toll-like receptor, a matrix metalloprotease, or
      the apoptosis facilitator BIM, also failed to alter neuron loss. CONCLUSION: We
      conclude that complement is not involved in the death and clearance of neurons in
      NPC disease. This study supports a view of neuroinflammation as a secondary
      response with non-causal relationship to neuron injury in the disease. This
      disease model may prove useful for understanding the conditions in which
      complement and immunity do contribute to neurodegeneration in other disorders.

PMID- 22985424
TI  - Rh(III)-catalyzed C-H bond activation along with "rollover" for the synthesis of
      4-azafluorenes.
AB  - An intramolecular reaction of 3-alkynyl and 3-alkenyl-2-arylpyridines selectively
      gave 4-azafluorene compounds in the presence of a catalytic amount of
      [Cp*RhCl(2)](2) and Cu(OAc)(2). Pyridine-directed C-H bond activation along with
      "rollover" are likely to be key steps of this transformation.

PMID- 22985425
TI  - Dermoscopy of discoid lupus erythematosus.
AB  - BACKGROUND: Dermoscopy is useful in evaluating skin tumours, but its
      applicability also extends into the field of inflammatory skin disorders. Discoid
      lupus erythematosus (DLE) represents the most common subtype of cutaneous lupus
      erythematosus. While dermoscopy and videodermoscopy have been shown to aid the
      differentiation of scalp DLE from other causes of scarring alopecia, limited data
      exist concerning dermoscopic criteria of DLE in other locations, such as the
      face, trunk and extremities. OBJECTIVE: To describe the dermoscopic criteria
      observed in a series of patients with DLE located on areas other than the scalp,
      and to correlate them to the underlying histopathological alterations. METHODS:
      DLE lesions located on the face, trunk and extremities were dermoscopically and
      histopathologically examined. Selection of the dermoscopic variables included in
      the evaluation process was based on data in the available literature on DLE of
      the scalp and on our preliminary observations. Analysis of data was done with
      SPSS analysis software. RESULTS: Fifty-five lesions from 37 patients with DLE
      were included in the study. Perifollicular whitish halo, follicular keratotic
      plugs and telangiectasias were the most common dermoscopic criteria. Statistical
      analysis revealed excellent correlation between dermoscopic and histopathological
      findings. Notably, a time-related alteration of dermoscopic features was
      observed. CONCLUSIONS: The present study provides new insights into the
      dermoscopic variability of DLE located on the face, trunk and extremities.

PMID- 22985426
TI  - A new species of Trichosomoididae (Nematoda) from skin of red snapper, Lutjanus
      campechanus (Perciformes: Lutjanidae), on the Texas-Louisiana shelf, northern
      Gulf of Mexico.
AB  - Eggs and larvae of Huffmanela oleumimica n. sp. infect red snapper, Lutjanus
      campechanus (Poey, 1860), were collected from the Texas-Louisiana Shelf (28
      degrees 16'36.58"N, 93 degrees 03'51.08"W) and are herein described using light
      and scanning electron microscopy. Eggs in skin comprised fields (1-5 * 1-12 mm;
      250 eggs/mm(2)) of variously oriented eggs deposited in dense patches or in
      scribble-like tracks. Eggs had clear (larvae indistinct, principally vitelline
      material), amber (developing larvae present) or brown (fully developed larvae
      present; little, or no, vitelline material) shells and measured 46-54 MUm (x =
      50; SD +/- 1.6; n = 213) long, 23-33 (27 +/- 1.4; 213) wide, 2-3 (3 +/- 0.5; 213)
      in eggshell thickness, 18-25 (21 +/- 1.1; 213) in vitelline mass width, and 36-42
      (39 +/- 1.1; 213) in vitelline mass length with protruding polar plugs 5-9 (7 +/-
      0.6; 213) long and 5-8 (6 +/- 0.5; 213) wide. Fully developed larvae were 160-201
      (176 +/- 7.9) long and 7-8 (7 +/- 0.5) wide, had transverse cuticular ridges, and
      were emerging from some eggs within and beneath epidermis. The new species
      differs from its congeners by having eggs <65 MUm in total length and that have a
      brown eggshell when fully developed, an envelope throughout development, and
      irregularly-dispersed eggshell spines plus a larva >110 MUm long with transverse
      cuticular ridges. The eggs lack a spindle-shaped envelope, polar filaments, and
      eggshell ridges. This is the first report of a species of Huffmanela from a
      snapper (Lutjanidae) or from the Gulf of Mexico. A table of egg and larval
      characteristics, hosts, and localities for Huffmanela spp. is provided.

PMID- 22985427
TI  - Does anonymity increase the reporting of mental health symptoms?
AB  - BACKGROUND: There is no doubt that the perceived stigma of having a mental
      disorder acts as a barrier to help seeking. It is possible that personnel may be
      reluctant to admit to symptoms suggestive of poor mental health when such data
      can be linked to them, even if their personal details are only used to help them
      access further care. This may be particularly relevant because individuals who
      have a mental health problem are more likely to experience barriers to care and
      hold stigmatizing beliefs. If that is the case, then mental health screening
      programmers may not be effective in detecting those most in need of care. We
      aimed to compare mental health symptom reporting when using an anonymous versus
      identifiable questionnaire among UK military personnel on deployment in Iraq.
      METHODS: Survey among UK military personnel using two questionnaires, one was
      anonymous (n = 315) and one collected contact details (i.e. identifiable, n =
      296). Distribution was by alternate allocation. Data were collected in Iraq
      during January-February 2009. RESULTS: No significant difference in the reporting
      of symptoms of common mental disorders was found (18.1% of identifiable vs. 22.9%
      of anonymous participants). UK military personnel were more likely to report sub
      threshold and probable PTSD when completing questionnaires anonymously (sub
      threshold PTSD: 2.4% of identifiable vs. 5.8% of anonymous participants; probable
      PTSD: 1.7% of identifiable vs. 4.8% of anonymous participants). Of the 11
      barriers to care and perceived social stigma statements considered, those
      completing the anonymous questionnaire compared to those completing the
      identifiable questionnaire were more likely to endorse three statements: "leaders
      discourage the use of mental health services" (9.3% vs. 4.6%), "it would be too
      embarrassing" (41.6% vs. 32.5%) and "I would be seen as weak" (46.6% vs. 34.2%).
      CONCLUSIONS: We found a significant effect on the reporting of sub-threshold and
      probable PTSD and certain stigmatizing beliefs (but not common mental disorders)
      when using an anonymous compared to identifiable questionnaire, with the
      anonymous questionnaire resulting in a higher prevalence of PTSD and increased
      reporting of three stigmatizing beliefs. This has implications for the conduct of
      mental health screening and research in the US and UK military.

PMID- 22985428
TI  - Adolescents' perceptions of music therapy following spinal fusion surgery.
AB  - AIMS AND OBJECTIVES: To explore adolescents' memories about music therapy after
      spinal fusion surgery and their recommendations for future patients. BACKGROUND:
      Spinal fusion for adolescent idiopathic scoliosis is one of the most painful
      surgeries performed. Music therapy is shown to decrease postoperative pain in
      children after minor surgery. In preparation for developing a preoperative
      information program, we interviewed adolescents who had spinal fusion and
      postoperative music therapy to find out what they remembered and what they
      recommended for future patients. METHODS: Eight adolescents who had spinal fusion
      for adolescent idiopathic scoliosis were interviewed about their experiences. For
      this qualitative study, the investigators independently used thematic analysis
      techniques to formulate interpretive themes. Together they discussed their ideas
      and assigned overall meanings to the information. RESULTS: The eight participants
      were 13-17 years of age and had surgery between 2-24 months previously. The
      overarching themes identified from the interviews were relaxation and pain
      perception, choice and control, therapist interaction and preoperative
      information. Participants stated that music therapy helped with mental relaxation
      and distraction from pain. It was important to be able to choose the type of
      music for the therapy and to use self-control to focus on the positive. Their
      recommendation was that future patients should be provided with information
      preoperatively about music therapy and pain management. Participants recommended
      a combination of auditory and visual information, especially the experiences of
      previous patients who had spinal fusion and music therapy. CONCLUSION: Music
      provided live at the bedside by a music therapist was remembered vividly and
      positively by most of the participants. RELEVANCE TO CLINICAL PRACTICE: The
      presence of a music therapist providing patient-selected music at the bedside is
      important. Methods to introduce adolescents to music therapy and how to use music
      for relaxation should be developed and tested.

PMID- 22985429
TI  - No GGGGCC-hexanucleotide repeat expansion in C9ORF72 in parkinsonism patients in
      Sweden.
AB  - An intronic GGGGCC-hexanucleotide repeat expansion in C9ORF72 was recently
      identified as a major cause of amyotrophic lateral sclerosis and frontotemporal
      dementia. Some amyotrophic lateral sclerosis patients have signs of parkinsonism,
      and many parkinsonism patients develop dementia. In this study we examined if the
      hexanucleotide repeat expansion was present in parkinsonism patients, to clarify
      if there could be a relationship between the repeat expansion and disease. We
      studied the size of the hexanucleotide repeat expansion in a well defined
      population-based cohort of 135 Parkinson's disease patients and 39 patients with
      atypical parkinsonism and compared with 645 Swedish control subjects. We found no
      correlation between Parkinson's disease or atypical parkinsonism and the size of
      the GGGGCC repeat expansion in C9ORF72. In conclusion, this GGGGCC-repeat
      expansion in C9ORF72 is not a cause of parkinsonism in the Swedish population.

PMID- 22985430
TI  - The relationship between limb dominance, disease lateralization and spread of
      weakness in amyotrophic lateral sclerosis (ALS).

PMID- 22985431
TI  - Gastrostomy use in motor neurone disease (MND): a review, meta-analysis and
      survey of current practice.
AB  - Abstract   Gastrostomy feeding is commonly used to support MND patients with
      dysphagia. In this paper we review three main methods of gastrostomy insertion
      (PEG, RIG, PIG); conduct a meta-analysis of mortality data following gastrostomy;
      and present a survey of current practice. A review of the literature revealed a
      lack of high quality evidence to indicate the optimal method and timing for
      gastrostomy insertion in patients with MND. A survey of 20 MND clinics
      demonstrated a clinic-based variability of gastrostomy practices due to factors
      such as clinician preference, availability of method, and patient respiratory
      function. The meta-analysis demonstrated that the estimate of the absolute
      difference in mortality rates was 2.1% higher for PEG (- 6.3%, + 11.2%),
      suggesting that RIG and PIG methods may be safer than PEG. These results and
      observations highlight the need for more research to evaluate and compare the
      safety of the differerent gastrostomy insertion methods in MND care.

PMID- 22985432
TI  - Dexpramipexole effects on functional decline and survival in subjects with
      amyotrophic lateral sclerosis in a Phase II study: subgroup analysis of
      demographic and clinical characteristics.
AB  - Our objective was to explore treatment effects in patient subgroups using post
      hoc analyses of data from part 2 of the dexpramipexole Phase II study. Subjects
      with amyotrophic lateral sclerosis (ALS) received dexpramipexole 300 mg/day or 50
      mg/day for 24 weeks. Treatment effects on the slope of the revised ALS Functional
      Rating Score (ALSFRS-R) and Combined Assessment of Function and Survival (CAFS)
      were evaluated in dichotomized subgroups: riluzole use, gender, site of symptom
      onset. Other subgroups were dichotomized using median baseline values for age,
      ALSFRS-R, slow vital capacity, symptom duration, diagnostic delay, and
      progression rate. Results showed that there was a 21% reduction in ALSFRS-R
      decline favoring the 300-mg vs. 50-mg arm (p = 0.177); mean CAFS ranking was
      significantly higher in the 300-mg vs. 50-mg arm (52.4 vs. 41.1; p = 0.046).
      Trends were recapitulated in virtually all subgroups. Generally, ALSFRS-R decline
      was reduced and CAFS rankings were higher in the 300-mg vs. 50-mg arm across
      subgroups. CAFS rankings were significantly higher in the 300-mg vs. 50-mg arm
      among subjects with ALSFRS-R scores <=35, symptom duration <18.7 months, or
      progression rate >= 0.7 points/month (p < 0.03). In conclusion, the observed
      benefit of 300- vs. 50-mg dexpramipexole on functional decline and survival was
      generally consistent among subjects regardless of baseline characteristics.

PMID- 22985433
TI  - Pyrimethamine decreases levels of SOD1 in leukocytes and cerebrospinal fluid of
      ALS patients: a phase I pilot study.
AB  - The mutated SOD1 protein appears to have a gene dose-dependent effect on the
      severity and progression of ALS. Lowering of SOD1 protein levels might reduce
      severity and progression of the disease. The antimalarial drug pyrimethamine
      (PYR) was identified to cause a dose-dependent reduction in SOD1 protein levels
      in human cells in vitro. To determine if there was a similar effect in humans, we
      performed a phase I pilot study in 16 ALS patients with SOD1 mutations, 18 weeks
      in duration. Blood samples were obtained during all visits. The actin normalized
      leukocyte SOD1 levels were analyzed using Western blot. SOD1 content in the
      cerebrospinal fluid (CSF) was determined by ELISA and the SOD1 enzymic activity
      by spectrophotometric analysis using KO2. Clinical assessment of disease severity
      was assessed using Appel ALS scale and ALSFRS-R. The leukocyte SOD1 levels showed
      a significant reduction (p > 0.0001) by the third study visit and this reduction
      was sustained throughout the remainder of the study. CSF also showed a decrease
      in SOD1 protein content and enzymic activity in the two patients so tested. Thus,
      PYR use may be associated with a reduction in SOD1 in ALS patients. The
      significance is uncertain and further detailed study is required.

PMID- 22985435
TI  - Small dense LDL is more susceptible to glycation than more buoyant LDL in Type 2
      diabetes.
AB  - Glycation of apoB (apolipoprotein B) of LDL (low-density lipoprotein) increases
      its atherogenicity. Concentrations of both serum glyc-apoB (glycated apoB) and SD
      LDL (small dense LDL) (syn LDL3; D=1.044-1.063 g/ml) are increased in diabetes
      and are closely correlated. We studied whether SD-LDL is more susceptible to
      glycation in vitro than more buoyant LDL in statin- and non-statin-treated Type 2
      diabetes mellitus. Serum SD-LDL apoB and glyc-apoB on statins was 20+/-2 (means+/
      S.D.) and 3.6+/-0.41 compared with 47+/-3 and 5.89+/-0.68 mg/dl in those not
      receiving statins (P<0.001 and <0.01, respectively). There was a dose-dependent
      increase in glycation on incubation of LDL subfractions with glucose, which was
      accompanied by an increase in LPO (lipid peroxide) and electrophoretic mobility
      and a decrease in free amino groups. SD-LDL was more susceptible to these changes
      than more buoyant LDL. Both SD-LDL and more buoyant LDL from statin-treated
      patients were less susceptible to glycation. There were fewer free amino groups
      on LDL subfractions from statin-treated patients, which may contribute to this
      resistance. In conclusion, greater susceptibility of SD-LDL to glycation is
      likely to contribute to the raised levels of circulating glyc-apoB in diabetes.
      Statins are associated with lower levels of both SD-LDL and glyc-apoB.

PMID- 22985434
TI  - Alzheimer disease and platelets: how's that relevant.
AB  - Alzheimer Disease (AD) is the most common neurodegenerative disorder worldwide,
      and account for 60% to 70% of all cases of progressive cognitive impairment in
      elderly patients. At the microscopic level distinctive features of AD are neurons
      and synapses degeneration, together with extensive amounts of senile plaques and
      neurofibrillars tangles. The degenerative process probably starts 20-30 years
      before the clinical onset of the disease. Senile plaques are composed of a
      central core of amyloid beta peptide, Abeta, derived from the metabolism of the
      larger amyloid precursor protein, APP, which is expressed not only in the brain,
      but even in non neuronal tissues. More than 30 years ago, some studies reported
      that human platelets express APP and all the enzymatic activities necessary to
      process this protein through the same pathways described in the brain. Since then
      a large number of evidence has been accumulated to suggest that platelets may be
      a good peripheral model to study the metabolism of APP, and the pathophysiology
      of the onset of AD. In this review, we will summarize the current knowledge on
      the involvement of platelets in Alzheimer Disease. Although platelets are
      generally accepted as a suitable model for AD, the current scientific interest on
      this model is very high, because many concepts still remain debated and
      controversial. At the same time, however, these still unsolved divergences mirror
      a difficulty to establish constant parameters to better defined the role of
      platelets in AD.

PMID- 22985436
TI  - The study of two barley type I-like MADS-box genes as potential targets of
      epigenetic regulation during seed development.
AB  - BACKGROUND: MADS-box genes constitute a large family of transcription factors
      functioning as key regulators of many processes during plant vegetative and
      reproductive development. Type II MADS-box genes have been intensively
      investigated and are mostly involved in vegetative and flowering development. A
      growing number of studies of Type I MADS-box genes in Arabidopsis, have assigned
      crucial roles for these genes in gamete and seed development and have
      demonstrated that a number of Type I MADS-box genes are epigenetically regulated
      by DNA methylation and histone modifications. However, reports on agronomically
      important cereals such as barley and wheat are scarce. RESULTS: Here we report
      the identification and characterization of two Type I-like MADS-box genes, from
      barley (Hordeum vulgare), a monocot cereal crop of high agronomic importance.
      Protein sequence and phylogenetic analysis showed that the putative proteins are
      related to Type I MADS-box proteins, and classified them in a distinct cereal
      clade. Significant differences in gene expression among seed developmental stages
      and between barley cultivars with varying seed size were revealed for both genes.
      One of these genes was shown to be induced by the seed development- and stress
      related hormones ABA and JA whereas in situ hybridizations localized the other
      gene to specific endosperm sub-compartments. The genomic organization of the
      latter has high conservation with the cereal Type I-like MADS-box homologues and
      the chromosomal position of both genes is close to markers associated with seed
      quality traits. DNA methylation differences are present in the upstream and
      downstream regulatory regions of the barley Type I-like MADS-box genes in two
      different developmental stages and in response to ABA treatment which may be
      associated with gene expression differences. CONCLUSIONS: Two barley MADS-box
      genes were studied that are related to Type I MADS-box genes. Differential
      expression in different seed developmental stages as well as in barley cultivars
      with different seed size was evidenced for both genes. The two barley Type I MADS
      box genes were found to be induced by ABA and JA. DNA methylation differences in
      different seed developmental stages and after exogenous application of ABA is
      suggestive of epigenetic regulation of gene expression. The study of barley Type
      I-like MADS-box genes extends our investigations of gene regulation during
      endosperm and seed development in a monocot crop like barley.

PMID- 22985438
TI  - Computational evidence that frequency trajectory theory does not oppose but
      emerges from age-of-acquisition theory.
AB  - According to the age-of-acquisition hypothesis, words acquired early in life are
      processed faster and more accurately than words acquired later. Connectionist
      models have begun to explore the influence of the age/order of acquisition of
      items (and also their frequency of encounter). This study attempts to reconcile
      two different methodological and theoretical approaches (proposed by Lambon Ralph
      & Ehsan, 2006 and Zevin & Seidenberg, 2002) to age-limited learning effects. The
      current simulations extend the findings reported by Zevin and Seidenberg (2002)
      that have shown that frequency trajectories (FTs) have limited and specific
      effects on word-reading tasks. Using the methodological framework proposed by
      Lambon Ralph and Ehsan (2006), which makes it possible to compare word-reading
      and picture-naming tasks in connectionist networks, we were able to show that FT
      has a considerable influence on age-limited learning effects in a picture naming
      task. The findings show that when the input-output mappings are arbitrary
      (simulating picture naming tasks), the links formed by the network become
      entrenched as a result of early experience and that subsequent variations in
      frequency of exposure of the items have only a minor impact. In contrast, when
      the mappings between input-output are quasi-systematic or systematic (simulating
      word-reading tasks), the training of new items was generalized and resulted in
      the suppression of age-limited learning effects. At a theoretical level, we
      suggest that FT, which simultaneously takes account of time and the level of
      exposure across time, represents a more precise and modulated measure compared
      with the order of introduction of the items and may lead to innovative hypotheses
      in the field of age-limited learning effects.

PMID- 22985437
TI  - Treatment of metabolic syndrome by combination of physical activity and diet
      needs an optimal protein intake: a randomized controlled trial.
AB  - BACKGROUND: The recommended dietary allowance (RDA) for protein intake has been
      set at 1.0-1.3 g/kg/day for senior. To date, no consensus exists on the lower
      threshold intake (LTI = RDA/1.3) for the protein intake (PI) needed in senior
      patients ongoing both combined caloric restriction and physical activity
      treatment for metabolic syndrome. Considering that age, caloric restriction and
      exercise are three increasing factors of protein need, this study was dedicated
      to determine the minimal PI in this situation, through the determination of
      albuminemia that is the blood marker of protein homeostasis. METHODS: Twenty
      eight subjects (19 M, 9 F, 61.8 +/- 6.5 years, BMI 33.4 +/- 4.1 kg/m2) with
      metabolic syndrome completed a three-week residential programme (Day 0 to Day 21)
      controlled for nutrition (energy balance of -500 kcal/day) and physical activity
      (3.5 hours/day). Patients were randomly assigned in two groups: Normal-PI (NPI:
      1.0 g/kg/day) and High-PI (HPI: 1.2 g/kg/day). Then, patients returned home and
      were followed for six months. Albuminemia was measured at D0, D21, D90 and D180.
      RESULTS: At baseline, PI was spontaneously 1.0 g/kg/day for both groups.
      Albuminemia was 40.6 g/l for NPI and 40.8 g/l for HPI. A marginal protein under
      nutrition appeared in NPI with a decreased albuminemia at D90 below 35 g/l (34.3
      versus 41.5 g/l for HPI, p < 0.05), whereas albuminemia remained stable in HPI.
      CONCLUSION: During the treatment based on restricted diet and exercise in senior
      people with metabolic syndrome, the lower threshold intake for protein must be
      set at 1.2 g/kg/day to maintain blood protein homeostasis.

PMID- 22985439
TI  - Hollow dentures: treatment option for atrophic ridges. a clinical report.
AB  - Severely atrophic ridges provide decreased retention, support, and stability and
      pose a clinical challenge to the success of complete denture prostheses. Extreme
      ridge resorption also increases the interridge distance. Restoration of the
      vertical dimension and esthetics thus demands increased height of the prosthesis
      and in turn leads to an increase in prosthesis weight. Reducing the weight of the
      denture enhances stability and retention and reduces further resorption of the
      jaw, thereby favoring the prognosis of the denture. This report describes the
      rehabilitation of an edentulous patient with resorbed maxillary and mandibular
      ridges and an increased interridge distance using simplified techniques of
      fabricating hollow dentures.

PMID- 22985440
TI  - Bicarbazoles: systematic structure-property investigations on a series of
      conjugated carbazole dimers.
AB  - A large series of conjugated carbazole dimers, namely bicarbazoles 1-12, were
      synthesized by Suzuki-Miyaura, Sonogashira, Hay, and McMurry coupling reactions.
      In 1-12, the two carbazole moieties are linked at the 1-, 2-, or 3-position
      directly or via an acetylenic or olefinic spacer. The structure-property
      relationships, particularly the effects of the conjugation connectivity and the
      pi-conjugated spacers on the electronic, photophysical, and electrochemical
      properties of 1-12, were studied by extensive UV-vis and fluorescence
      spectroscopic measurements, cyclic voltammetry (CV), and theoretical calculations
      as well as X-ray crystallographic analyses. The connection at the 1-position of
      carbazole ensures high extent of pi-conjugation, while that at the 3-position
      enhances the electron-donating ability. Both acetylenic and olefinic spacers
      allow the extension of pi-conjugation, and the latter also causes the increase of
      the donor ability. Moreover, the structural variations were found to affect the
      fluorescence quantum yields significantly, which are up to 0.84.

PMID- 22985441
TI  - Adolescent urology--a specialty in development.

PMID- 22985442
TI  - Reactions of the cationic zinc thiolate model complex [Zn(Tab)4](PF6)2 with N
      donor ligands and cobalt dichloride.
AB  - Reactions of [Zn(Tab)(4)](PF(6))(2) (Tab = 4-(trimethylammonio)benzenethiolate)
      (1) with 2,2'-bipyridine (2,2'-bipy), 1,10-phenanthroline (phen), 2,9-dimethyl
      1,10-phenanthroline (2,9-dmphen), N-methylimidazole (N-Meim), and 2,6-bis(pyrazol
      3-yl)pyridine (bppy) or with CoCl(2).6H(2)O at the presence of N-donor ligands
      (2,2'-bipy, phen, 4,4'-dimethyl-2,2'-bipyridine (4,4'-dmbpy), 2,6-bis(3,5
      dimethyl-1H-pyrazol-1-yl)pyridine (bdmppy))gave rise to a family of zinc or
      cobalt thiolate complexes, [Zn(Tab)(2)(L)](PF(6))(2) (2: L = 2,2'-bipy, 3: L =
      phen, 4: L = 2,9-dmphen), [Zn(Tab)(2)(N-Meim)(2)](PF(6))(2) (5),
      [Zn(Tab)(2)(bppy)](PF(6))(2) (6), [Co(Tab)(2)(L)(2)](PF(6))(3) (7: L = 2,2'-bipy,
      8: L = phen, 9: L = 4,4'-dmbpy), and [Co(Tab)(bdmppy)Cl](PF(6)) (10). These
      compounds were characterized by elemental analysis, IR spectra, UV-vis
      spectra,(1)H NMR, electrospray ionization (ESI) mass spectra, and single-crystal
      X-ray diffraction. The Zn(II) in [Zn(Tab)(2)L(n)](2+)dications of 2-5 is
      tetrahedrally coordinated by two Tab ligands and one L or two N-Meim ligands. In
      6, the Zn(II) has a distorted trigonal-bipyramidal geometry, coordinated by two
      Tab ligands and one tridentate bppy ligand. The Co(III) in the
      [Co(Tab)(2)(L)(2)](3+) trications of 7-9 is octahedraly chelated by two bidentate
      L ligands and two Tab ligands. In 10, the Co(II) adopts a distorted trigonal
      bipyramidal geometry, coordinated by one Cl(-), one Tab ligand, and one
      tridentate bdmppy. In the formation of 2-6, two Tab ligands are removed from the
      [Zn(Tab)(4)](2+) dication when it is attacked by L ligands, while in the cases of
      7-9, the Zn(II) of the [Zn(Tab)(4)](2+) dication was replaced by Co(III) (derived
      from oxidation of Co(II) by O(2)) followed by the removal of two Tab ligands via
      L ligands. In the case of 10, the central Zn(II) of the [Zn(Tab)(4)](2+) dication
      was displaced by Co(II) followed by the removal of three Tab ligands via one Cl(
      ) and one tridentate bdmppy. These ligand and metal replacement reactions may
      provide some interesting information on the interactions of the [Zn(S-Cys)(4)](2
      ) unit of Zn-MTs with N-heterocyclic ligands and toxic metal ions encountered in
      a natural environment.

PMID- 22985444
TI  - Prucalopride: evaluation of the pharmacokinetics, pharmacodynamics, efficacy and
      safety in the treatment of chronic constipation.
AB  - INTRODUCTION: Prucalopride is the first member of a novel class of 5-HT(4)
      receptor agonist which has been extensively evaluated for the treatment of
      chronic constipation. Predominantly, prucalopride is currently used to treat
      patients that show an insufficient response to laxatives as an alternative form
      of therapy. AREAS COVERED: The following article provides the reader with a
      systematic review of the literature on prucalopride. Specifically, the article
      reviews the currently literature on the pharmacokinetics and the pharmacodynamics
      of the drugs as well as reviewing literature on its efficacy. Furthermore, the
      authors also highlight the safety and tolerability of the drug that have been
      demonstrated in its clinical development. EXPERT OPINION: Prucalopride is an
      important addition to the therapeutic abilities for treating chronic
      constipation, especially in females poorly responding to laxatives. The safety
      profile of the drug, to date, is favorable. There is also the possibility that
      prucalopride might be of benefit to other disorders of gastrointestinal motility
      with a number of studies currently in progress, which are evaluating alternative
      applications.

PMID- 22985445
TI  - Conformationally distinct five-coordinate heme-NO complexes of soluble guanylate
      cyclase elucidated by multifrequency electron paramagnetic resonance (EPR).
AB  - Soluble guanylate cyclase (sGC) is a heme-containing enzyme that senses nitric
      oxide (NO). Formation of a heme Fe-NO complex is essential to sGC activation, and
      several spectroscopic techniques, including electron paramagnetic resonance (EPR)
      spectroscopy, have been aimed at elucidating the active enzyme conformation. Of
      these, only EPR spectra (X-band ~9.6 GHz) have shown differences between low- and
      high-activity Fe-NO states, and these states are modeled in two different heme
      domain truncations of sGC, beta1(1-194) and beta2(1-217), respectively
      (Derbyshire et al., Biochemistry 2008, 47, 3892-3899). The EPR signal of the low
      activity sGC Fe-NO complex exhibits a broad lineshape that has been interpreted
      as resulting from site-to-site inhomogeneity, and simulated using g strain, a
      continuous distribution about the principal values of a given g tensor. This
      approach, however, fails to account for visible features in the X-band EPR
      spectra as well as the g anisotropy observed at higher microwave frequencies.
      Herein we analyze X-, Q-, and D-band EPR spectra and show that both the broad
      lineshape and the spectral structure of the sGC EPR signal at multiple microwave
      frequencies can be simulated successfully with a superposition of only two
      distinct g tensors. These tensors represent different populations that likely
      differ in Fe-NO bond angle, hydrogen bonding, or the geometry of the amino acid
      residues. One of these conformations can be linked to a form of the enzyme with
      higher activity.

PMID- 22985446
TI  - Role of splenectomy in patients with hepatocellular carcinoma and hypersplenism.
AB  - INTRODUCTION: Hypersplenism with thrombocytopenia is a common complication of
      cirrhosis with portal hypertension. We evaluated the role of splenectomy in
      patients with hepatocellular carcinoma (HCC) in terms of the improvement of
      biochemical indices and liver volume. METHODS: Nineteen patients with HCC
      underwent liver resection and splenectomy from January 2000 to December 2009.
      Thirty-nine patients who underwent liver resection during the same period were
      enrolled as case-matched controls. We performed a retrospective review of
      prospectively collected data. We analysed the results of biochemical tests,
      disease-free survival and overall survival and measured the liver volume before
      and at 90 days after operation. RESULTS: Preoperative white blood cell counts (P
      = 0.001), platelet counts (P = 0.021), total bilirubin (P <= 0.001) and
      prothrombin time by international normalized ratio (P = 0.043) were significantly
      different. However, these results had converged to similar levels 90 days after
      the operation. The degree of increment in liver volume were similar (P = 0.763).
      In splenectomy group, portal vein thrombosis developed in eight patients and all
      patients except one recovered using only conservative treatments. There was an
      operative mortality because of liver failure by thrombosis. CONCLUSIONS: Although
      splenectomy may induce thrombosis, liver failure and subsequent mortality,
      splenectomy may improve liver function and expand the indication of liver
      resection if postoperative management is conducted conservatively.

PMID- 22985447
TI  - Distribution of emergency operations and trauma in a Swedish hospital: need for
      reorganisation of acute surgical care?
AB  - BACKGROUND: Subspecialisation within general surgery has today reached further
      than ever. However, on-call time, an unchanged need for broad surgical skills are
      required to meet the demands of acute surgical disease and trauma. The
      introduction of a new subspecialty in North America that deals solely with acute
      care surgery and trauma is an attempt to offer properly trained surgeons also
      during on-call time. To find out whether such a subspecialty could be helpful in
      Sweden we analyzed our workload for emergency surgery and trauma. METHODS:
      Linkoping University Hospital serves a population of 257 000. Data from 2010 for
      all patients, diagnoses, times and types of operations, surgeons involved,
      duration of stay, types of injury and deaths regarding emergency procedures were
      extracted from a prospectively-collected database and analyzed. RESULTS: There
      were 2362 admissions, 1559 emergency interventions; 835 were mainly abdominal
      operations, and 724 diagnostic or therapeutic endoscopies. Of the 1559 emergency
      interventions, 641 (41.1%) were made outside office hours, and of 453 minor or
      intermediate procedures (including appendicectomy, cholecystectomy, or
      proctological procedures) 276 (60.9%) were done during the evenings or at night.
      Two hundred and fifty-four patients were admitted with trauma and 29 (11.4%)
      required operation, of whom general surgeons operated on eight (3.1%). Thirteen
      consultants and 11 senior registrars were involved in 138 bowel resections and
      164 cholecystectomies chosen as index operations for standard emergency surgery.
      The median (range) number of such operations done by each consultant was 6 (3-17)
      and 6 (1-22). Corresponding figures for senior registrars were 7 (0-11) and 8 (1
      39). CONCLUSION: There was an uneven distribution of exposure to acute surgical
      problems and trauma among general surgeons. Some were exposed to only a few
      standard emergency interventions and most surgeons did not operate on a single
      patient with trauma. Further centralization of trauma care, long-term positions
      at units for emergency surgery and trauma, and subspecialisation in the fields of
      emergency surgery and trauma, might be options to solve problems of low volumes.

PMID- 22985448
TI  - Adherence to sublingual immunotherapy in preschool children.

PMID- 22985449
TI  - Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the
      rational design of new triazolyl-amidine derivatives.
AB  - Recently, many efforts have been made to develop N-methyl-D-aspartic acid
      receptor antagonists for treating different pathological conditions such as
      thrombo-embolic stroke, traumatic head injury, Huntington's, Parkinson's, and
      Alzheimer's diseases). However, as side-effects limit the use of most
      antagonists, new drugs are still required. In this work, we performed a
      (quantitative) structure-activity relationship analysis of 17 phenyl-amidine
      derivatives (1a-1q), reported as N-methyl-D-aspartic acid receptor antagonists,
      and used this data to rationally design the triazolyl-amidines. The best
      (quantitative) structure-activity relationship model constructed by multiple
      linear regression analysis presented high data fitting (R = 0.914) was able to
      explain 83.6% of the biological data variance (R(2) = 0.836), presented a
      satisfactory internal predictive ability (Q(2) = 0.609) and contained the
      descriptors (E(HOMO), Ovality and cLogP). Our assays confirmed that glutamate
      promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected
      the neurons from the glutamate effect (from 77% to 27% and 45%, respectively).
      The results of neurotoxicity and cytotoxicity on Vero cells suggested the
      favorable profile of 2a and 2b. Also, the molecular modeling used to predict the
      activity, the interaction with the receptor and the pharmacokinetic and toxicity
      of the triazolyl-amidines pointed them as a promising class for further
      exploration as N-methyl-D-aspartic acid receptor antagonists.

PMID- 22985450
TI  - Acceptance of the 2012 Clark P. Read Mentor Award: Mentoring Then and Now.

PMID- 22985451
TI  - Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in
      patients with psoriasis and chronic viral hepatitis B or C: a retrospective,
      multicentre study in a clinical setting.
AB  - BACKGROUND: Both the safety and efficacy of biologic therapy may be affected in
      the presence of highly prevalent chronic viral hepatitis. OBJECTIVE: To evaluate
      the safety and effectiveness of ustekinumab and antitumour necrosis factor
      therapy in patients with psoriasis and concomitant chronic viral hepatitis.
      METHODS: This was a retrospective, multicentre study. Twenty-five patients with
      psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B
      virus (HBV) (five patients) infection who had received at least one biologic
      agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four;
      infliximab, two) were included. Clinical, imaging and laboratory data were
      recorded. RESULTS: In the case of HCV infection, the majority of the patients did
      not exhibit increases in their viral load or serum liver tests. Aspartate
      aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were
      doubled from the baseline measurement in only one patient treated with
      etanercept. Two other cases exhibited viral load increases during the follow-up
      period. In total, 18 of the 26 treatments achieved a 75% improvement in their
      Psoriasis Area and Severity Index (PASI 75) score during the follow-up period.
      Two patients treated with etanercept were diagnosed with hepatocellular
      carcinoma. In the case of HBV infection, all of the patients were being treated
      with antiviral therapy, and none presented significant variations in viral load
      or serum liver enzymes. All patients achieved a PASI 75 during follow-up.
      CONCLUSIONS: Biologic therapy was effective and safe for the majority of our
      patients with HCV and HBV infection, although there may be a risk of reactivation
      or aggravation. We describe the first cases to receive ustekinumab. The use of
      biologics should be limited to those cases in which the risk-benefit ratio is
      justified.

PMID- 22985452
TI  - Frontline healthcare providers' views of depression and its prevention in older
      adults.
AB  - AIMS AND OBJECTIVES: To describe healthcare providers' views on depression and
      its prevention in older people. BACKGROUND: There is an urgent need to develop
      public health approaches to depression prevention in older adults because of the
      growing older population and the high rate of depression among community-dwelling
      older adults in Taiwan. Prior studies have focused on the prevalence of and risk
      factors for depression in Taiwanese community-dwelling older adults. Research
      from the viewpoints of prevention and healthcare providers is needed to guide
      these approaches. DESIGN: A qualitative study involving semi-structured
      interviews. METHODS: A purposive sample of 25 healthcare providers was recruited
      from a city in northern Taiwan. Data were collected through in-depth individual
      interviews and analysed using thematic analysis. RESULTS: Results were embedded
      within four major themes: lack of children's support, maladaptation to
      distressing life circumstances in late life, innate vulnerability in the
      individuals and being unaware of or reluctant to accept an illness. CONCLUSIONS:
      Participants' accounts of depression and its prevention were conceptualised
      within the family and socio-cultural contexts older adults lived in. Lack of
      children's support was reported as a main contributor to depression in older
      adults. Society was reported as the main context in which depression prevention
      intervention should take place. Communal activities were described as important
      for mental wellness and depression prevention. RELEVANCE TO CLINICAL PRACTICE:
      Study findings show how family, Chinese culture and socio-economic circumstances
      influence accounts of depression and its prevention in older adults. Attention to
      the cultural construction of meanings may help extend our vision beyond a focus
      on the biomedical discourse and promote innovative ways of tackling depression
      that match the policy goals with the needs of older adults and community.

PMID- 22985453
TI  - Thromboprophylaxis among Australasian colorectal surgeons.
AB  - BACKGROUND: Thromboembolism is a common cause of morbidity and mortality in
      patients with colorectal cancer, but thromboprophylaxis (TP) is underutilized.
      Current guidelines do not make specific recommendations for colorectal cancer
      patients and provide minimal guidance for the ambulatory setting, although
      emerging evidence suggests TP may be warranted during chemoradiotherapy or in the
      extended post-operative phase. A survey of Australasian colorectal surgeons was
      therefore performed to assess current TP practice and attitudes. METHODS: An
      online survey was sent to 204 surgeons who were members of the Colorectal
      Surgical Society of Australia and New Zealand. RESULTS: One hundred twenty-eight
      surgeons (63%) completed the survey. Most surgeons consult available guidelines,
      and where recommendations are made, current practice is in line with them. Lack
      of data, lack of ownership, logistical issues and an absence of guideline
      recommendations currently prevent surgeons from instituting TP in the neoadjuvant
      treatment period. Fifty-four per cent of surgeons currently prescribe TP after
      hospital discharge; those that do not, cite logistical issues as the main
      constraint. CONCLUSION: More data on thromboembolism risk during various
      treatment phases are required and should be promulgated in tumour-specific
      guidelines. Logistical barriers to adopting TP in the ambulatory setting should
      be addressed.

PMID- 22985454
TI  - Bacteriophages are synergistic with bacterial interference for the prevention of
      Pseudomonas aeruginosa biofilm formation on urinary catheters.
AB  - AIMS: We hypothesized that pretreating urinary catheters with benign Escherichia
      coli HU2117 plus an antipseudomonal bacteriophage (PhiE2005-A) would prevent
      Pseudomonas aeruginosa biofilm formation on catheters--a pivotal event in the
      pathogenesis of catheter-associated urinary tract infection (CAUTI). METHODS AND
      RESULTS: Silicone catheter segments were exposed to one of four pretreatments
      (sterile media; E. coli alone; phage alone; E. coli plus phage), inoculated with
      P. aeruginosa and then incubated up to 72 h in human urine before rinsing and
      sonicating to recover adherent bacteria. Pseudomonas aeruginosa adherence to
      catheters was almost 4 log(10) units lower when pretreated with E. coli plus
      phage compared to no pretreatment (P < 0.001) in 24-h experiments and more than 3
      log(10) units lower in 72-h experiments (P < 0.05). Neither E. coli nor phage
      alone generated significant decreases. CONCLUSIONS: The combination of phages
      with a pre-established biofilm of E. coli HU2117 was synergistic in preventing
      catheter colonization by P. aeruginosa. SIGNIFICANCE AND IMPACT OF THE STUDY: We
      describe a synergistic protection against colonization of urinary catheters by a
      common uropathogen. Escherichia coli-coated catheters are in clinical trials;
      adding phage may offer additional benefit.

PMID- 22985455
TI  - Action of specific thyroid hormone receptor alpha(1) and beta(1) antagonists in
      the central and peripheral regulation of thyroid hormone metabolism in the rat.
AB  - BACKGROUND: The iodine-containing drug amiodarone (Amio) and its noniodine
      containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous
      in vivo and in vitro studies have shown that the major metabolite of Amio,
      desethylamiodarone, acts as a thyroid hormone receptor (TR) alpha(1) and beta(1)
      antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a
      selective TRalpha(1) antagonist. In the present study, Amio and Dron were used as
      tools to discriminate between TRalpha(1) or TRbeta(1) regulated genes in central
      and peripheral thyroid hormone metabolism. METHODS: Three groups of male rats
      received either Amio, Dron, or vehicle by daily intragastric administration for 2
      weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and
      thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3
      mRNA expressions and activities, and thyroid hormone transporters monocarboxylate
      transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion
      transporter 1C1 (OATP1C1). RESULTS: Amio treatment decreased serum T(3), while
      serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control
      rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio
      treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression,
      while increasing pituitary TSHbeta and MCT10 mRNA expression. Amio decreased the
      pituitary D2 activity. By contrast, Dron treatment resulted in decreased
      hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3)
      concentration decreased substantially compared to Dron and control rats (50%,
      p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1,
      mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver
      MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. CONCLUSION:
      Our results suggest an important role for TRalpha1 in the regulation of
      hypothalamic TRH mRNA expression, whereas TRbeta plays a dominant role in
      pituitary and liver thyroid hormone metabolism.

PMID- 22985456
TI  - Why New Orleans matters.

PMID- 22985457
TI  - Resuscitation and perioperative management of the high-risk single ventricle
      patient: first-stage palliation.
AB  - Infants born with hypoplastic left heart syndrome or other lesions resulting in a
      single right ventricle face the highest risk of mortality among all forms of
      congenital heart disease. Before the modern era of surgical palliation, these
      conditions were universally lethal; recent refinements in surgical technique and
      perioperative management have translated into dramatic improvements in survival.
      Nonetheless, these infants remain at a high risk of morbidity and mortality, and
      an appreciation of single ventricle physiology is fundamental to the care of
      these high-risk patients. Herein, resuscitation and perioperative management of
      infants with hypoplastic left heart syndrome are reviewed. Basic neonatal and
      pediatric life support recommendations are summarized, and perioperative first
      stage clinical management strategies are reviewed.

PMID- 22985459
TI  - Hemitruncus arteriosus: cardiac magnetic resonance angiography findings.
AB  - Hemitruncus arteriosus (HA) is an uncommon congenital cardiac malformation in
      which one pulmonary artery branch originates from the ascending aorta. A 2-month
      old male was referred to our hospital for failure to thrive, cyanosis, and
      tachypnea. A chest radiograph demonstrated moderate cardiomegaly and
      peribronchial thickening. Echocardiography demonstrated right atrial and
      ventricular enlargement and increased gradient (25 mm Hg) in the right pulmonary
      artery. Cardiac magnetic resonance angiography was performed and clearly revealed
      typical imaging findings of a right HA which had complex cardiac and vascular
      anatomy. This case report presents cardiac magnetic resonance angiography
      findings of HA.

PMID- 22985460
TI  - Platypnea-orthodeoxia syndrome after failed percutaneous closure of secundum
      atrial septal defect.
AB  - We report a 51-year-old patient with platypnea-orthodeoxia syndrome after
      percutaneous closure of a secundum atrial septal defect, an unusual complication
      of this modality of treatment. Echocardiography, the main diagnostic technique in
      the present case, showed that one of the percutaneous device's rims was fixed to
      the anterior wall of the inferior cava vein. Furthermore it showed that the blood
      flowed from the inferior cava vein, through the defect in the atrial septum, into
      the left atria.

PMID- 22985461
TI  - Direct alpha-arylation of alpha-amino carbonyl compounds with indoles using
      visible light photoredox catalysis.
AB  - A general and mild method for the construction of functionalized 2-(1H-indol-3
      yl)-2-amino-carbonyl compounds was achieved, which represents the first example
      of direct alpha-arylation of alpha-amino carbonyl compounds with indoles using
      the visible light photoredox catalysis strategy.

PMID- 22985463
TI  - Theoretical and experimental investigations on hypoelectronic
      heterodimetallaboranes of group 6 transition metals.
AB  - Density functional theory (DFT) has been used to probe the bonding and electronic
      properties of dimolybdaborane [(Cp*Mo)(2)B(5)H(9)], 1 (Cp* = eta(5)-C(5)Me(5)),
      and several other heterodimolybdaborane clusters, such as [(Cp*Mo)(2)B(5)(MU(3)
      OEt)H(7)] (2), [(Cp*Mo)(2)B(5)(MU(3)-OEt)(n-BuO)H(6)] (3), [(eta(5)
      C(5)H(5)W)(2)B(4)H(4)S(2)] (4), and [(Cp*Mo)(2)B(4)H(4)E(2)] (5-7, where, for 5,
      E = S, for 6, E = Se, and for 7, E = Te). The DFT results were also used to
      address some key points such as (i) the metal-metal bond length, (ii) the
      location and number of bridging and terminal hydrogen atoms, (iii) the molecular
      orbital analysis, and (iv) the assignment of (11)B and (1)H NMR chemical shifts.
      These studies further provide meticulous insight into similarities and
      differences between various dimetallaborane clusters 1-7. In addition, the
      crystal structures of 5 and 7 are reported, which come on top of the already
      existing literature of dimetallaboranes and support the theoretical findings.

PMID- 22985462
TI  - NBS1 plays a synergistic role with telomerase in the maintenance of telomeres in
      Arabidopsis thaliana.
AB  - BACKGROUND: Telomeres, as elaborate nucleo-protein complexes, ensure chromosomal
      stability. When impaired, the ends of linear chromosomes can be recognised by
      cellular repair mechanisms as double-strand DNA breaks and can be healed by non
      homologous-end-joining activities to produce dicentric chromosomes. During cell
      divisions, particularly during anaphase, dicentrics can break, thus producing
      naked chromosome tips susceptible to additional unwanted chromosome fusion. Many
      telomere-building protein complexes are associated with telomeres to ensure their
      proper capping function. It has been found however, that a number of repair
      complexes also contribute to telomere stability. RESULTS: We used Arabidopsis
      thaliana to study the possible functions of the DNA repair subunit, NBS1, in
      telomere homeostasis using knockout nbs1 mutants. The results showed that
      although NBS1-deficient plants were viable, lacked any sign of developmental
      aberration and produced fertile seeds through many generations upon self
      fertilisation, plants also missing the functional telomerase (double mutants),
      rapidly, within three generations, displayed severe developmental defects.
      Cytogenetic inspection of cycling somatic cells revealed a very early onset of
      massive genome instability. Molecular methods used for examining the length of
      telomeres in double homozygous mutants detected much faster telomere shortening
      than in plants deficient in telomerase gene alone. CONCLUSIONS: Our findings
      suggest that NBS1 acts in concert with telomerase and plays a profound role in
      plant telomere renewal.

PMID- 22985464
TI  - IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS
      demyelinating disease.
AB  - BACKGROUND: Theiler's virus infection induces chronic demyelinating disease in
      mice and has been investigated as an infectious model for multiple sclerosis
      (MS). IL-1 plays an important role in the pathogenesis of both the autoimmune
      disease model (EAE) and this viral model for MS. However, IL-1 is known to play
      an important protective role against certain viral infections. Therefore, it is
      unclear whether IL-1-mediated signaling plays a protective or pathogenic role in
      the development of TMEV-induced demyelinating disease. METHODS: Female C57BL/6
      mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO) were infected with Theiler's
      murine encephalomyelitis virus (1 x 106 PFU). Differences in the development of
      demyelinating disease and changes in the histopathology were compared. Viral
      persistence, cytokine production, and immune responses in the CNS of infected
      mice were analyzed using quantitative PCR, ELISA, and flow cytometry. RESULTS:
      Administration of IL-1beta, thereby rending resistant B6 mice susceptible to TMEV
      induced demyelinating disease, induced a high level of Th17 response.
      Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6) mice
      also induced TMEV-induced demyelinating disease. High viral persistence was found
      in the late stage of viral infection in IL-1R-deficient mice, although there were
      few differences in the initial anti-viral immune responses and viral persistent
      levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN
      responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV
      infected IL-1R-deficient mice, leading to deficiencies in T cell function that
      permit viral persistence. CONCLUSIONS: These results suggest that the presence of
      high IL-1 level exerts the pathogenic role by elevating pathogenic Th17
      responses, whereas the lack of IL-1 signals promotes viral persistence in the
      spinal cord due to insufficient T cell activation by elevating the production of
      inhibitory cytokines and regulatory molecules. Therefore, the balance of IL-1
      signaling appears to be extremely important for the protection from TMEV-induced
      demyelinating disease, and either too much or too little signaling promotes the
      development of disease.

PMID- 22985465
TI  - Learning phonemes with a proto-lexicon.
AB  - Before the end of the first year of life, infants begin to lose the ability to
      perceive distinctions between sounds that are not phonemic in their native
      language. It is typically assumed that this developmental change reflects the
      construction of language-specific phoneme categories, but how these categories
      are learned largely remains a mystery. Peperkamp, Le Calvez, Nadal, and Dupoux
      (2006) present an algorithm that can discover phonemes using the distributions of
      allophones as well as the phonetic properties of the allophones and their
      contexts. We show that a third type of information source, the occurrence of
      pairs of minimally differing word forms in speech heard by the infant, is also
      useful for learning phonemic categories and is in fact more reliable than purely
      distributional information in data containing a large number of allophones. In
      our model, learners build an approximation of the lexicon consisting of the high
      frequency n-grams present in their speech input, allowing them to take advantage
      of top-down lexical information without needing to learn words. This may explain
      how infants have already begun to exhibit sensitivity to phonemic categories
      before they have a large receptive lexicon.

PMID- 22985466
TI  - Multiple linear epitopes (B-cell, CTL and Th) of JEV expressed in recombinant MVA
      as multiple epitope vaccine induces a protective immune response.
AB  - Epitope-based vaccination might play an important role in the protective immunity
      against Japanese encephalitis virus (JEV) infection. The purpose of the study is
      to evaluate the immune characteristics of recombinant MVA carrying multi-epitope
      gene of JEV (rMVA-mep). The synthetic gene containing critical epitopes (B-cell,
      CTL and Th) of JEV was cloned into the eukaryotic expression vector pGEM-K1L, and
      the rMVA-mep was prepared. BALB/c mice were immunized with different dosages of
      purified rMVA-mep and the immune responses were determined in the form of
      protective response against JEV, antibodies titers (IgG1 and IgG2a), spleen cell
      lymphocyte proliferation, and the levels of interferon-gamma and interleukin-4
      cytokines. The results showed that live rMVA-mep elicited strongly immune
      responses in dose-dependent manner, and the highest level of immune responses was
      observed from the groups immunized with 107 TCID50 rMVA-mep among the
      experimental three concentrations. There were almost no difference of cytokines
      and neutralizing antibody titers among 107 TCID50 rMVA-mep, recombinant ED3 and
      inactivated JEV vaccine. It was noteworthy that rMVA-mep vaccination potentiates
      the Th1 and Th2-type immune responses in dose-dependent manner, and was
      sufficient to protect the mice survival against lethal JEV challenge. These
      findings demonstrated that rMVA-mep can produce adequate humoral and cellular
      immune responses, and protection in mice, which suggested that rMVA-mep might be
      an attractive candidate vaccine for preventing JEV infection.

PMID- 22985467
TI  - Reconstruction with scrotal skin flaps after wide local resection of penoscrotal
      extramammary Paget's disease.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Both the treatment and reconstruction after
      resection of penoscrotal extramammary Paget's disease (EMPD) are of concern among
      oncological urologists. Reconstruction of large skin defects after wide local
      resection of this disease remains challenging and skilled work. For the first
      time, by using scrotal skin flaps, we have introduced an effective and reliable
      procedure into the new area of reconstruction for penoscrotal EMPD in selected
      patients, with satisfactory functional and aesthetic results. OBJECTIVE: * To
      introduce an effective procedure for reconstruction of large skin defects after
      wide local resection of penoscrotal extramammary Paget's disease (EMPD) in
      selected patients using scrotal skin flaps without compromising oncological
      control. PATIENTS AND METHODS: * From January to June 2010 this procedure was
      carried out in five selected patients with penoscrotal EMPD who underwent wide
      local resection with subsequent reconstruction using scrotal skin flaps. *
      Patient demographics, lesion characteristics, surgical margins and outcomes were
      evaluated. * Skin defects covered 48-96 cm(2) (median = 72 cm(2)). The median
      (range) duration of follow-up was 24 (22-27) months. RESULTS: * Flaps survived
      with satisfactory functional and aesthetic results. * All patients survived
      without local or systemic recurrence of tumour. CONCLUSIONS: * Wide local
      resection can provide cure in superficial penoscrotal EMPD. * The described
      method using scrotal skin flaps seems to be a safe and effective procedure for
      the reconstruction of large defects.

PMID- 22985468
TI  - Spirobacillenes A and B, unusual spiro-cyclopentenones from Lysinibacillus
      fusiformis KMC003.
AB  - Two previously unreported spiro-cyclopentenones, spirobacillenes A (1) and B (2),
      were isolated from the 24 h broth culture of Lysinibacillus fusiformis KMC003
      derived from acidic coal-mine drainage. The structures of 1 and 2 were elucidated
      by analyses of the NMR, HRFABMS, single-crystal X-ray diffraction
      crystallography, and circular dichroism (CD) spectral data. Compound 1 possessed
      moderate inhibitory activity against the production of nitric oxide (NO) and
      reactive oxygen species (ROS).

PMID- 22985469
TI  - Angiotensin II potentiates alpha-adrenergic vasoconstriction in the elderly.
AB  - Aging is characterized by increased sympatho-excitation, expressed through both
      the alpha-adrenergic and RAAS (renin-angiotensin-aldosterone) pathways. Although
      the independent contribution of these two pathways to elevated vasoconstriction
      with age may be substantial, significant cross-talk exists that could produce
      potentiating effects. To examine this interaction, 14 subjects (n=8 young, n=6
      old) underwent brachial artery catheterization for administration of AngII
      (angiotensin II; 0.8-25.6 ng/dl per min), NE [noradrenaline (norepinephrine); 2.5
      80 ng/dl per min] and AngII with concomitant alpha-adrenergic antagonism [PHEN
      (phentolamine); 10 MUg/dl per min]. Ultrasound Doppler was utilized to determine
      blood flow, and therefore vasoconstriction, in both infused and contralateral
      (control) limbs. Arterial blood pressure was measured directly, and sympathetic
      nervous system activity was assessed via microneurography and plasma NE analysis.
      AngII sensitivity was significantly greater in the old, indicated by both greater
      maximal vasoconstriction (-59+/-4% in old against -48+/-3% in young) and a
      decreased EC50 (half-maximal effective concentration) (1.4+/-0.2 ng/dl per min in
      old against 2.6+/-0.7 MUg/dl per min in young), whereas the maximal NE-mediated
      vasoconstriction was similar between these groups (-58+/-9% in old and -62+/-5%
      in young). AngII also increased venous NE in the old group, but was unchanged in
      the young group. In the presence of alpha-adrenergic blockade (PHEN), maximal
      AngII-mediated vasoconstriction in the old was restored to that of the young (
      43+/-8% in old and -39+/-6% in young). These findings indicate that, with healthy
      aging, the increased AngII-mediated vasoconstriction may be attributed, in part,
      to potentiation of the alpha-adrenergic pathway, and suggest that cross-talk
      between the RAAS and adrenergic systems may be an important consideration in
      therapeutic strategies targeting these two pathways.

PMID- 22985470
TI  - Solution structure of decorin-binding protein A from Borrelia burgdorferi.
AB  - Decorin-binding protein A (DBPA) is an important lipoprotein from the bacterium
      Borrelia burgdorferi, the causative agent of Lyme disease. The absence of DBPA
      drastically reduces the pathogenic potential of the bacterium, and biochemical
      evidence indicates DBPA's interactions with the glycosaminoglycan (GAG) portion
      of decorin are crucial to its function. We have determined the solution structure
      of DBPA and studied DBPA's interactions with various forms of GAGs. DBPA is
      determined to be a helical bundle protein consisting of five helices held
      together by a strong hydrophobic core. The structure also possesses a basic patch
      formed by portions of two helices and two flexible linkers. Low-molecular mass
      heparin-induced chemical shift perturbations for residues in the region as well
      as increases in signal intensities of select residues in their presence confirm
      residues in the pocket are perturbed by heparin binding. Dermatan sulfate
      fragments, the dominant GAG type found on decorin, were shown to have lower
      affinity than heparin but are still capable of binding DBPA.

PMID- 22985471
TI  - Is self-rated health a valid measure to use in social inequities and health
      research? Evidence from the PAPFAM women's data in six Arab countries.
AB  - INTRODUCTION: Some evidence from high-income countries suggests that self-rated
      health (SRH) is not a consistent predictor of objective health across social
      groups, and that its use may lead to inaccurate estimates of the effects of
      inequities on health. Given increased interest in studying and monitoring social
      inequities in health worldwide, the aim of the present study was to evaluate the
      validity of SRH as a consistent measure of health across socioeconomic categories
      in six Arab countries. METHODS: We employed the PAPFAM population-based survey
      data on women from Morocco, Algeria, Tunisia, Lebanon, Syria, and the Occupied
      Palestinian Territories (OPT). Multivariate logistic regression analyses were
      performed to assess the strength of the association between fair/poor SRH and
      objective health (reporting at least one chronic condition), adjusting for
      available socio-demographic and health-related variables. Analyses were then
      stratified by two socioeconomic indicators: education and household economic
      status. RESULTS: The association between SRH and objective health is strong in
      Algeria, Tunisia, Lebanon, Syria, and OPT, but weak in Morocco. The strength of
      the association between reporting fair/poor health and objective health was not
      moderated by education or household economic status in any of the six countries.
      CONCLUSION: As the SRH-objective health association does not vary across social
      categories, the use of the measure in social inequities in health research is
      justified. These results should not preclude the need to carry out other
      validation studies using longitudinal data on men and women, or the need to
      advocate for improving the quality of morbidity and mortality data in the Arab
      region.

PMID- 22985472
TI  - Nonlinear optimization for drift removal in estimation of gait kinematics based
      on accelerometers.
AB  - A new data processing method is described for estimation of angles of leg
      segments, joint angles, and trajectories in the sagittal plane from data recorded
      by sensors units mounted at the lateral side of leg segments. Each sensor unit
      comprises a pair of three-dimensional accelerometers which send data wirelessly
      to a PC. The accelerometer signals comprise time-varying and temperature
      dependent offset, which leads to drift and diverged signals after integration.
      The key features of the proposed method are to model the offset by a slowly
      varying function of time (a cubic spline polynomial) and evaluate the polynomial
      coefficients by nonlinear numerical simplex optimization with the goal to reduce
      the drift in processed signals (angles and movement displacements). The angles
      and trajectories estimated by our method were compared with angles measured by an
      optical motion capture system. The comparison shows that the errors for angles
      (rms) were below 4 degrees  and the errors in stride length were below 2%. The
      algorithm developed is applicable for real-time and off-line analysis of gait.
      The method does not need any adaptation with respect to gait velocity or
      individuality of gait.

PMID- 22985473
TI  - Lower extremity sagittal joint moment production during split-belt treadmill
      walking.
AB  - The split-belt treadmill (SBT) has recently been used to rehabilitate locomotor
      asymmetries in clinical populations. However, the joint mechanics produced while
      walking on a SBT are not well-understood. The purpose of this study was to
      investigate the lower extremity sagittal joint moment patterns produced by each
      limb during SBT walking and provide insight as to how these joint moment patterns
      may be useful in rehabilitating unilateral gait deficits. Thirteen healthy young
      volunteers walked on the SBT with the belts tied and in a "SPLIT" session in
      which one belt moved twice as fast as the other. Sagittal lower extremity joint
      moment and ground reaction force impulses were then calculated over the braking
      and propulsive phases of the gait cycle. Paired t-tests were performed to analyze
      magnitude differences between conditions (i.e. the fast and slow limbs during
      SPLIT vs. the same limb during tied-belt walking) and between the fast and slow
      limbs during SPLIT. During the SPLIT session, the fast limb produced higher
      ground reaction force and ankle moment impulses during the propulsive and braking
      phases, and lower knee moment impulses during the propulsive phase when compared
      to the slow limb. The knee moment impulse was also significantly higher during
      braking in the slow limb than in the fast limb. The mechanics of each limb during
      the SPLIT session also differed from the mechanics observed when the belt speeds
      were tied. Based on these findings, we suggest that each belt may have intrinsic
      value in rehabilitating specific unilateral locomotor deficits.

PMID- 22985474
TI  - Skin anisotropy in vivo and initial natural stress effect: a quantitative study
      using high-frequency static elastography.
AB  - BACKGROUND: Most studies on skin anisotropy are carried out in an "average"
      context, e.g. with an extension/compression test on the skin in vivo, the elastic
      modulus being estimated for the stretched zone overall. Furthermore, the natural
      tension of the skin is not taken into account either in the experimental
      protocols or in the models studied. In this study, a battery of elastographic
      tests was carried out to investigate forearm skin anisotropy quantitatively by
      measuring local through-thickness strain in the dermis by means of high frequency
      elastography. The biaxial tensile effect and influence of the natural forearm
      skin tension were also analyzed. METHODS: The elastographic test was carried out
      using a combination of an extensiometer device and a real time ultrasound
      scanner. The extensiometer was used to apply a stress cycle, i.e. stretching,
      holding and release, on the internal face of the forearm in vivo. Parallel to the
      mechanical test, 2D real time ultrasound acquisitions were performed to track
      local displacements and to estimate local through-thickness strain using an
      elastographic algorithm. Local through-thickness strain kinetics were then
      extracted and used as a quantified indicator. We studied anisotropy in two
      stretching situations: stretching parallel and stretching perpendicular to
      Langer's lines. Elastographic tests were performed for two upper arm/forearm
      angles, i.e. outstretched and bent forearm, in order to check the natural skin
      tension effect. RESULTS: The results showed the effectiveness of elastographic
      tests to describe and quantify the anisotropic behavior of the forearm skin in
      vivo. Elastographic results were distinctly different according to forearm
      positions: the anisotropic behavior was reversed from the bent forearm to the
      outstretched forearm. CONCLUSIONS: The local anisotropic behavior of the skin in
      vivo could be easily studied using the elastographic test. Nevertheless, the
      initial skin tension is an important parameter which strongly affects the
      mechanical behavior of the skin in vivo, in particular its anisotropic
      properties.

PMID- 22985475
TI  - Does loading velocity affect failure strength after tendon repair?
AB  - Tensile testing of repaired tendons has been used to assess the efficacy of
      repair techniques. However, individuals flex and extend fingers at rates higher
      than those typically used for testing. This study characterized the effect of
      loading rate on the failure strength of repaired canine flexor tendons. Thirty
      six canine flexor digitorum profundus tendons were lacerated, repaired, and
      tested at three displacement rates: 0.33 mm/s; 84 mm/s; and 590 mm/s. Peak force
      and stiffness of the repairs were evaluated. Peak force was significantly greater
      (p<0.05) for tendons distracted at 590 mm/s than at 0.33 mm/s. Crosshead
      stiffness was significantly greater for tendons distracted at 590 mm/s than at
      either 84 mm/s or 0.33 mm/s. The predominant failure mode was core suture knot
      untying. Distracting tendons at slow loading rates provides a conservative
      assessment of tendon repair strength. Additionally, an estimate of the failure
      load of this repair for different clinical events has been identified.

PMID- 22985476
TI  - Manipulating failure mechanism of rapid prototyped scaffolds by changing nodal
      connectivity and geometry of the pores.
AB  - The performance of cellular solids in biomedical applications relies strongly on
      a detailed understanding of the effects of pore topology on mechanical
      properties. This study aims at characterizing the failure mechanism of scaffolds
      based on nodal connectivity (number of struts that meet in joints) and geometry
      of the pores. Plastic models of scaffolds having the same relative density but
      different cubic and trigonal unit cells were designed and then fabricated via
      three dimensional (3-D) printing. Unit cells were repeated in different
      arrangements in 3-D space. An in-situ imaging technique was utilized to study the
      progressive deformation of the scaffold models. Different nodal connectivities
      resulted in a wide range of compressive behaviors in scaffold models, from
      elastic-plastic to fully brittle. The Maxwell necessary criterion for rigidity
      was used to explain mechanical behavior of the scaffolds. Nodal connectivity of 4
      satisfied Maxwell's criterion for rigidity in the examined structures. In a
      stress-strain curve of scaffolds with cubic unit cells and nodal connectivities
      of 3 and 4, pore deformation was observed after yielding. On the other hand,
      scaffolds with trigonal unit cells and nodal connectivities of 4 and 6, exhibited
      brittle behavior in the absence of pore deformation. These results highlight the
      role of nodal connectivity on failure mechanism and subsequently mechanical
      performance of scaffolds. This study reveals that appropriate pore geometry can
      provide sufficient condition for rigidity when Maxwell's necessary condition is
      satisfied. In addition, this study demonstrates that Maxwell's criterion can be
      used in pre-designing of pore geometries for scaffolds with distinct nodal
      connectivities.

PMID- 22985477
TI  - Murine skin and vaginal mucosa are similarly susceptible to infection by
      pseudovirions of different papillomavirus classifications and species.
AB  - Depending upon viral genotype, productive papillomavirus infection and disease
      display preferential tropism for cutaneous or mucosal stratified squamous
      epithelia, although the mechanisms are unclear. To investigate papillomavirus
      entry tropism, we used reporter pseudovirions based on various cutaneous and
      mucosal papillomavirus species, including the recently identified murine
      papillomavirus. Pseudovirus transduction of BALB/c mice was examined using an
      improved murine skin infection protocol and a previously developed cervicovaginal
      challenge model. In the skin, HPV5, HPV6, HPV16, BPV1 and MusPV1 pseudovirions
      preferentially transduced keratinocytes at sites of trauma, similar to the
      genital tract. Skin infection, visualized by in vivo imaging using a luciferase
      reporter gene, peaked between days 2-3 and rapidly diminished for all
      pseudovirion types. Murine cutaneous and genital tissues were similarily
      permissive for pseudovirions of HPV types 5, 6, 8, 16, 18, 26, 44, 45, 51, 58 and
      animal papillomaviruses BPV1 and MusPV1, implying that papillomavirus' tissue and
      host tropism is governed primarily by post-entry regulatory events in the mouse.

PMID- 22985478
TI  - The Prehospital assessment of severe trauma patients' performed by the specialist
      ambulance nurse in Sweden - a phenomenographic study.
AB  - BACKGROUND: A common feature of prehospital emergency care is the short and
      fragmentary patient encounters with increased demands for efficient and rapid
      treatment. Crucial decisions are often made and the premise is the specialist
      ambulance nurse's ability to capture the situation instantaneously. The
      assessment is therefore a pre-requisite for decisions about appropriate actions.
      However, the low exposure to severe trauma cases in Sweden leads to vulnerability
      for the specialist ambulance nurse, which makes the assessment more difficult.
      Our objective was to describe specialist ambulance nurses' perceptions of
      assessing patients exposed to severe trauma. METHODS: This study had a
      phenomenographic approach and was performed in 2011 as an interview study. 15
      specialist ambulance nurses with a minimum of 2.5 years of experience from praxis
      were included. The analysis of data was performed using phenomenography according
      to Marton. RESULTS: The perceptions of assessing patients exposed to severe
      trauma were divided into: To be prepared for emergency situations, Confidence in
      one's own leadership and Developing professional knowledge. CONCLUSIONS: This
      study reveals that the specialist ambulance nurse, on the scene of accident,
      finds the task of assessment of severe trauma patients difficult and complicated.
      In some cases, even exceeding what they feel competent to accomplish. The
      specialist ambulance nurses feel that no trauma scenarios are alike and that more
      practical skills, more training, exercise and feedback are needed.

PMID- 22985480
TI  - Type 2 innate lymphoid cells: new players in asthma and allergy.
AB  - Two years ago, T helper cells, including Th1, Th2 and Th17 cells, were considered
      to be the most significant sources of cytokine during the orchestration of immune
      responses in the lung. Following the discovery of innate lymphoid cells, we now
      know that these previously unappreciated cytokine-secreting cells, including ILC1
      (IFN-gamma-expressing NK cells), ILC2 (IL-5 and IL-13-expressing nuocytes) and
      RORgamma ILC (IL-17 and IL-22-expressing 'ILC3') are important mediators in
      immune processes. Herein we review the role of ILC2 specifically in inflammatory
      lung responses with special attention to allergen-induced and viral-induced type
      2 lung disease.

PMID- 22985481
TI  - Dihydroazulene-buckminsterfullerene conjugates.
AB  - The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has recently
      attracted interest as a molecular switch for molecular electronics. In this
      field, Buckminsterfullerene, C(60), has been shown to be a useful anchoring group
      for adhering a molecular wire to an electrode. Here we have combined the two
      units with the overall aim to elucidate how C(60) influences the DHA-VHF
      switching events. Efficient synthetic protocols for making covalently linked DHA
      C(60) conjugates were developed, using Prato, Sonogashira, Hay, and Cadiot
      Chodkiewicz reactions. These syntheses provide as well a variety of potentially
      useful DHA and C(60) building blocks for acetylenic scaffolding. The two units
      were separated by bridges of various lengths, such as oligo(phenyleneethynylene)
      (OPE2 and OPE3) wires. The distance of separation was found to influence strongly
      the light-induced ring-opening reaction of DHA to its corresponding VHF. Thus,
      C(60) was found to significantly quench this conversion when situated closely to
      the DHA unit.

PMID- 22985482
TI  - Homology models of human all-trans retinoic acid metabolizing enzymes CYP26B1 and
      CYP26B1 spliced variant.
AB  - Homology models of CYP26B1 (cytochrome P450RAI2) and CYP26B1 spliced variant were
      derived using the crystal structure of cyanobacterial CYP120A1 as template for
      the model building. The quality of the homology models generated were carefully
      evaluated, and the natural substrate all-trans-retinoic acid (atRA), several
      tetralone-derived retinoic acid metabolizing blocking agents (RAMBAs), and a well
      known potent inhibitor of CYP26B1 (R115866) were docked into the homology model
      of full-length cytochrome P450 26B1. The results show that in the model of the
      full-length CYP26B1, the protein is capable of distinguishing between the natural
      substrate (atRA), R115866, and the tetralone derivatives. The spliced variant of
      CYP26B1 model displays a reduced affinity for atRA compared to the full-length
      enzyme, in accordance with recently described experimental information.

PMID- 22985479
TI  - Creating genetic resistance to HIV.
AB  - HIV/AIDS remains a chronic and incurable disease, in spite of the notable
      successes of combination antiretroviral therapy. Gene therapy offers the prospect
      of creating genetic resistance to HIV that supplants the need for antiviral
      drugs. In sight of this goal, a variety of anti-HIV genes have reached clinical
      testing, including gene-editing enzymes, protein-based inhibitors, and RNA-based
      therapeutics. Combinations of therapeutic genes against viral and host targets
      are designed to improve the overall antiviral potency and reduce the likelihood
      of viral resistance. In cell-based therapies, therapeutic genes are expressed in
      gene modified T lymphocytes or in hematopoietic stem cells that generate an HIV
      resistant immune system. Such strategies must promote the selective proliferation
      of the transplanted cells and the prolonged expression of therapeutic genes. This
      review focuses on the current advances and limitations in genetic therapies
      against HIV, including the status of several recent and ongoing clinical studies.

PMID- 22985483
TI  - Validation of the modified allergic rhinitis and its impact on asthma (ARIA)
      severity classification in allergic rhinitis children: the PEDRIAL study.
AB  - BACKGROUND: A modified allergic rhinitis and its impact on asthma (ARIA) (m-ARIA)
      criterion to classify the severity of allergic rhinitis (AR) has recently been
      validated in both treated and untreated adult patients; however, such information
      in children is lacking. The aim of this study was to validate this m-ARIA
      severity criterion, which allows for discrimination between moderate and severe
      AR, in a large pediatric patient sample population. METHODS: The m-ARIA
      classification categorizes AR severity into mild (no affected items), moderate (1
      3 affected items), and severe (all four affected items). We applied this modified
      criterion to untreated AR pediatric patients aged 6-12 years, through an
      observational, cross-sectional, and multicenter study. AR symptoms were assessed
      using the Total Four Symptom Score (T4SS), and the severity was evaluated by both
      ARIA severity items and visual analogue scale (VAS). RESULTS: Allergic rhinitis
      pediatric patients (N = 1269) from 271 centers were included. Among them, 59.5%
      had intermittent and 40.5% persistent disease; 89.9% had moderate/severe AR using
      the original ARIA (o-ARIA) classification and 59.5% had moderate, while 30.5% had
      severe AR using the m-ARIA criterion. Using the m-ARIA, significantly higher T4SS
      and VAS scores were obtained when comparing severe with moderate AR. CONCLUSIONS:
      The m-ARIA severity classification is a useful clinical tool to discriminate
      moderate from severe AR among untreated pediatric patients.

PMID- 22985484
TI  - Lithium-associated hypercalcemia and hyperparathyroidism in the elderly: what do
      we know?
AB  - BACKGROUND: Lithium has been reported to induce hypercalcemia and
      hyperparathyroidism, yet few studies have examined the impact on older patients.
      We therefore undertook this review and report our findings. METHOD: We undertook
      a systematic review of articles on lithium-associated hypercalcemia and/or
      hyperparathyroidism that were identified via electronic English language database
      searches through PubMed. RESULTS: Among reported cases and case series of lithium
      associated hyperparathyroidism in which ages of specific subjects were provided,
      40% of affected individuals were over age 60. Mean serum calcium levels are
      reported to be higher in lithium treated patients over age 60 compared with
      younger patients. While many patients who develop lithium-associated
      hypercalcemia and hyperparathyroidism are asymptomatic, symptomatic complications
      may be more of a concern in older patients, especially in those with co-morbid
      renal disease. LIMITATIONS: To date, all cross-sectional studies of lithium
      associated hypercalcemia and hyperparathyroidism are of mixed age group cohorts
      and more specific studies focused on older patients have yet to be performed.
      CONCLUSIONS: Lithium-induced hypercalcemia and hyperparathyroidism are under
      recognized potential complications of lithium therapy which may occur more
      frequently in older patients. Psychiatrists should be vigilant in screening for
      hypercalcemia and hyperparathyroidism in their older patients receiving lithium,
      both prior to starting treatment and at least annually thereafter.

PMID- 22985485
TI  - Quantitative assessment of motor abnormalities in untreated patients with major
      depressive disorder.
AB  - The primary purpose of this study was to examine motor physiology disturbances in
      a group of patients with untreated major depressive disorder using sensitive
      instrumental procedures. The secondary aim of the study was to examine the
      relationship of the affective symptom state to these motor assessments. The
      authors studied 40 individuals meeting DSM-IV criteria for unipolar major
      depressive disorder and 40 healthy comparison subjects. Electromechanical
      measures of force steadiness (FS), simple reaction time (RT), movement time (MT)
      and scaling of movement velocity to distance (velocity scaling, VS) were
      performed. The authors found that performance on the force steadiness, movement
      time, and velocity scaling measures was significantly poorer in the subjects with
      depression. There was no difference between the groups on the measure of reaction
      time. The force steadiness, reaction time, movement time, and velocity scaling
      scores were not associated with affective state. This study demonstrates that
      motor abnormalities suggestive of basal ganglia dysfunction occur in many
      patients with major depressive disorder, and that these abnormalities may exist
      in the absence of current psychotropic medication treatment. The finding of
      impaired movement time and velocity scaling in the presence of normal reaction
      time suggests a neuromotor or parkinsonian pathophysiology for slowness in
      depression.

PMID- 22985486
TI  - The clinical effectiveness of evidence-based interventions for depression: a
      pragmatic trial in routine practice.
AB  - BACKGROUND: Controversy persists about how effectively empirically-supported
      treatments for major depression work in actual clinical practice as well as how
      patients choose among them. We examined the acute phase effectiveness of
      cognitive therapy (CT), interpersonal psychotherapy (IPT), and combined
      psychotherapy-pharmacotherapy (PHT) in a naturalistic setting, allowing patients
      their choice of treatment. METHODS: The study compared CT (n=63), IPT (n=56), CT
      PHT (n=34), and IPT-PHT (n=21) for 174 subjects with major depression in a
      secondary care mood disorders clinic. Patient preference, rather than
      randomization, determined treatment selection. The Beck Depression Inventory-II
      (BDI) was the primary outcome variable. Exclusion criteria were minimal. RESULTS:
      All treatments were associated with a reduction in depressive symptoms, with a
      35% remission rate by week 26. Overall improvement was well within ranges
      reported in efficacy trials. On average, treatment effects of the different
      interventions straddled the same range, but moderation analyses revealed that BDI
      scores dropped faster in the first 16 weeks in patients who received CT alone
      than patients who received CT and pharmacotherapy, a pattern not found in
      patients who received IPT (with or without pharmacotherapy). LIMITATIONS:
      Limitations consist of a modest sample size, choice of treatment was made by
      participants which may have been influenced by many sources, and the absence of a
      non-active control group. CONCLUSIONS: This study supports the effectiveness of
      empirically-supported antidepressant treatments selected by patients in routine
      settings, and provides an indication that speed of therapeutic response may vary
      amongst treatments.

PMID- 22985487
TI  - Enteroviruses isolated from herpangina and hand-foot-and-mouth disease in Korean
      children.
AB  - Hand-foot-and-mouth disease (HFMD) and herpangina are commonly prevalent illness
      in young children. They are similarly characterized by lesions on the skin and
      oral mucosa. Both diseases are associated with various enterovirus serotypes. In
      this study, enteroviruses from patients with these diseases in Korea in 2009 were
      isolated and analyzed. Demographic data for patients with HFMD and herpangina
      were compared and all enterovirus isolates were amplified in the VP1 region by
      reverse transcription-polymerase chain reaction and sequenced. Among the
      enterovirus isolates, prevalent agents were coxsackievirus A16 in HFMD and
      coxsackievirus A5 in herpangina. More prevalent months for HFMD were June (69.2%)
      and May (11.5%), and June (40.0%) and July (24.0%) for herpangina. Age prevalence
      of HFMD patients with enterovirus infection was 1 year (23.1%), 4 years (19.2%),
      and over 5 years (19.2%). However, the dominant age group of herpangina patients
      with enterovirus infection was 1 year (48.0%) followed by 2 years (28.0%).
      Comparison of pairwise VP1 nucleotide sequence alignment of all isolates within
      the same serotypes revealed high intra-type variation of CVA2 isolates (84.6
      99.3% nucleotide identity). HFMD and herpangina showed differences in demographic
      data and serotypes of isolated enteroviruses, but there was no notable difference
      in amino acid sequences by clinical syndromes in multiple comparison of the
      partial VP1 gene sequence.

PMID- 22985488
TI  - Follicular variant of papillary thyroid carcinoma presenting as toxic nodule in
      an adolescent: coexistent polymorphism of the TSHR and Gsalpha genes.
AB  - BACKGROUND: Autonomously functioning, "hot", thyroid nodules are not common in
      children and adolescents. Such nodules are not considered alarming because they
      are assumed to be benign adenomas. Herein, we present a 15-year-old girl with a
      papillary thyroid carcinoma of 3.5 cm in diameter, which was functionally
      autonomous and scintigraphically hot. PATIENT FINDINGS: The patient, initially
      referred to our Endocrine Unit because of a thyroid nodule, returned 6 months
      later for symptoms of hyperthyroidism. Hyperthyroidism was confirmed
      biochemically. Radioactive iodine ((131)I) thyroid scintigraphy was consistent
      with an autonomous thyroid nodule. As per guidelines, the patient underwent
      surgery and a pathological examination revealed papillary carcinoma, follicular
      variant. The excised nodule was examined for activating mutations of the
      thyrotropin receptor (TSHR), Gsalpha (GNAS1), H-RAS, N-RAS, K-RAS, and BRAF genes
      by direct sequencing. No mutations were found. Nevertheless, two combined
      nonfunctioning mutations were detected: a single-nucleotide polymorphism (SNP) of
      the TSHR gene, in exon 7, at codon 187 (AAT->AAC, both encoding asparagine), and
      a SNP within exon 8 of the Gsalpha gene at codon 185 (ATC->ATT, both encoding
      isoleucine). Both SNPs were also identified in the germline DNA of the patient.
      The same SNPs were sought in the parents and brother of our patient. Her father
      was heterozygous for the TSHR SNP, her mother heterozygous for the Gsalpha SNP,
      and her brother was wild type. CONCLUSIONS: This case demonstrates that the
      presence of hyperfunctioning thyroid nodule(s) does not rule out cancer and
      warrants careful evaluation, especially in childhood and adolescence to overlook
      malignancy.

PMID- 22985489
TI  - Mobility for care workers: job changes and wages for nurse aides.
AB  - The long-term care industry in the United States faces serious recruitment and
      retention problems among nurse aides. At the same time, these low-wage workers
      may feel trapped in poorly-paid jobs from which they would do well to leave.
      Despite this tension, not enough is known about how workers fare when they leave
      (or stay in) such care work. Using longitudinal data from the Survey of Income
      and Program Participation for the years 1996-2003, we examine the relationship
      between different job and occupational mobility patterns and wage outcomes for
      nurse aides, focusing on which job transitions offer better opportunities to earn
      higher wages and on whether job transition patterns differ by race. Our results
      confirm high turnover among nurse aides, with 73 percent of the sample working in
      occupations other than nurse aide at some point during the survey time frame.
      About half of respondents that transition out of nurse aide work move into higher
      paying occupations, although the percentage of transitions to higher paying
      occupations drops to 35 percent when nurse aides that become RNs are excluded.
      Among black workers especially, wage penalties for moving into other jobs in the
      low-wage labor market appear to be rather small, likely a factor in high turnover
      among nurse aides. The findings illustrate the importance of occupation-specific
      mobility trajectories and their outcomes for different groups of workers, and for
      understanding the constrained decisions these workers make.

PMID- 22985490
TI  - Social networks--the future for health care delivery.
AB  - With the rapid growth of online social networking for health, health care systems
      are experiencing an inescapable increase in complexity. This is not necessarily a
      drawback; self-organising, adaptive networks could become central to future
      health care delivery. This paper considers whether social networks composed of
      patients and their social circles can compete with, or complement, professional
      networks in assembling health-related information of value for improving health
      and health care. Using the framework of analysis of a two-sided network--patients
      and providers--with multiple platforms for interaction, we argue that the
      structure and dynamics of such a network has implications for future health care.
      Patients are using social networking to access and contribute health information.
      Among those living with chronic illness and disability and engaging with social
      networks, there is considerable expertise in assessing, combining and exploiting
      information. Social networking is providing a new landscape for patients to
      assemble health information, relatively free from the constraints of traditional
      health care. However, health information from social networks currently
      complements traditional sources rather than substituting for them. Networking
      among health care provider organisations is enabling greater exploitation of
      health information for health care planning. The platforms of interaction are
      also changing. Patient-doctor encounters are now more permeable to influence from
      social networks and professional networks. Diffuse and temporary platforms of
      interaction enable discourse between patients and professionals, and include
      platforms controlled by patients. We argue that social networking has the
      potential to change patterns of health inequalities and access to health care,
      alter the stability of health care provision and lead to a reformulation of the
      role of health professionals. Further research is needed to understand how
      network structure combined with its dynamics will affect the flow of information
      and potentially the allocation of health care resources.

PMID- 22985491
TI  - Combined targeting of MEK/MAPK and PI3K/Akt signalling in multiple myeloma.
AB  - So-called RAS-dependent pathways, such as those signalling via mitogen-activated
      protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) and
      phosphoinositide-3 kinase (PI3K)/Akt, are implicated in proliferation and
      survival of multiple myeloma (MM) cells. However, the effects of their combined
      blockade and its potential therapeutic utility for the treatment of RAS-mutated
      MM have not systematically been analysed. Here, we tested the functional
      consequences of single versus combined inhibition of the MEK/MAPK and PI3K/Akt
      pathways in a large series of primary MM samples (n = 55) and MM cell lines (n =
      11). Additionally, the anti-myeloma activity of different treatments was analysed
      with respect to the RAS mutation status. PI3K/Akt blockade was generally more pro
      apoptotic than blockade of MEK/MAPK both in cell lines and in primary MM samples.
      Simultaneous blockade of both pathways led to significantly enhanced anti-myeloma
      activity in 75% of primary MM samples, whereas the remainder was largely
      resistant. Resistance to combination blockade was exclusively observed in RAS
      wildtype cases, whereas sensitivity was noted in RAS wildtype and in RAS mutated
      MM. These results suggest that oncogenic RAS is a predictor of sensitivity to
      combination treatment with PI3K/Akt and MEK/MAPK inhibitors and that such an
      approach might therefore be beneficial for this genetically well-defined subgroup
      of MM patients.

PMID- 22985492
TI  - Effect of handover on the outcomes of small bowel obstruction in an acute care
      surgery model.
AB  - BACKGROUND: An acute care surgery (ACS) model was introduced to manage emergency
      surgical presentations efficiently. The aim of this study was to evaluate the
      impact of patient handover in an ACS model on the outcomes of adhesive small
      bowel obstruction (SBO). METHODS: A retrospective study was performed on patients
      who were admitted with adhesive SBO at Prince of Wales Hospital. The cohort
      consisted of all patients treated by the ACS team from its introduction in
      September 2005 to February 2011. Patients in the ACS cohort were divided into two
      groups: those whose care was handed over to another surgeon and those whose care
      was not. These groups of patients were compared with a random sample of 50
      patients in the pre-ACS period. RESULTS: In the ACS period, there was no
      significant difference in complication rates or length of hospital stay in those
      who were not handed over and those who were. A significantly higher proportion of
      operations took place during the day for the group who had been handed over
      (72.7% versus 36.7%; P = 0.005). There were no significant differences in
      complication rates or length of hospital stay in the pre-ACS and ACS period.
      CONCLUSION: Management under an ACS team does not increase adverse outcomes for
      adhesive SBO. Patients can be safely handed over within an ACS framework. Other
      members of the ACS team may help facilitate continuity of care.

PMID- 22985493
TI  - Common genetic variants associated with disease from genome-wide association
      studies are mutually exclusive in prostate cancer and rheumatoid arthritis.
AB  - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The link between
      inflammation and cancer has long been reported and inflammation is thought to
      play a role in the pathogenesis of many cancers, including prostate cancer
      (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have
      reported numerous susceptibility loci that predispose individuals to many
      different traits. The present study aims to ascertain if there are common genetic
      risk profiles that might predispose individuals to both PrCa and the autoimmune
      inflammatory condition, rheumatoid arthritis. These results could have potential
      public heath impact in terms of screening and chemoprevention. OBJECTIVES: To
      investigate if potential common pathways exist for the pathogenesis of autoimmune
      disease and prostate cancer (PrCa). To ascertain if the single nucleotide
      polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being
      associated with susceptibility to PrCa are also associated with susceptibility to
      the autoimmune disease rheumatoid arthritis (RA). MATERIALS AND METHODS: The
      original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was
      expanded to include a total of 3221 cases and 5272 controls. In all, 37 germline
      autosomal SNPs at genome-wide significance associated with PrCa risk were
      identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for
      these 37 SNPs between RA cases and controls using a chi-squared trend test and
      corrected for multiple testing (Bonferroni). RESULTS: In all, 33 SNPs were able
      to be analysed in the RA dataset. Proxies could not be located for the SNPs in
      3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for
      the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained
      statistically significant evidence for association (P = 6 * 10(-4) ; odds ratio
      [OR] = 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis.
      However, further analyses showed that the association of this allele was due to
      confounding by RA-associated HLA-DRB1 alleles. CONCLUSIONS: There is currently no
      evidence that SNPs associated with PrCa at genome-wide significance are
      associated with the development of RA. Studies like this are important in
      determining if common genetic risk profiles might predispose individuals to many
      diseases, which could have implications for public health in terms of screening
      and chemoprevention.

PMID- 22985494
TI  - Preserved vascular integrity and enhanced survival following neuropilin-1
      inhibition in a mouse model of CD8 T cell-initiated CNS vascular permeability.
AB  - BACKGROUND: Altered permeability of the blood-brain barrier (BBB) is a feature of
      numerous neurological conditions including multiple sclerosis, cerebral malaria,
      viral hemorrhagic fevers and acute hemorrhagic leukoencephalitis. Our laboratory
      has developed a murine model of CD8 T cell-initiated central nervous system (CNS)
      vascular permeability in which vascular endothelial growth factor (VEGF)
      signaling plays a prominent role in BBB disruption. FINDINGS: In this study, we
      addressed the hypothesis that in vivo blockade of VEGF signal transduction
      through administration of peptide (ATWLPPR) to inhibit neuropilin-1 (NRP-1) would
      have a therapeutic effect following induction of CD8 T cell-initiated BBB
      disruption. We report that inhibition of NRP-1, a co-receptor that enhances
      VEGFR2 (flk-1) receptor activation, decreases vascular permeability, brain
      hemorrhage, and mortality in this model of CD8 T cell-initiated BBB disruption.
      We also examine the expression pattern of VEGFR2 (flk-1) and VEGFR1 (flt-1) mRNA
      expression during a time course of this condition. We find that viral infection
      of the brain leads to increased expression of flk-1 mRNA. In addition, flk-1 and
      flt-1 expression levels decrease in the striatum and hippocampus in later time
      points following induction of CD8 T cell-mediated BBB disruption. CONCLUSION:
      This study demonstrates that NRP-1 is a potential therapeutic target in neuro
      inflammatory diseases involving BBB disruption and brain hemorrhage.
      Additionally, the reduction in VEGF receptors subsequent to BBB disruption could
      be involved in compensatory negative feedback as an attempt to reduce vascular
      permeability.

PMID- 22985495
TI  - Efficacy and safety of high-dose vitamin C on complex regional pain syndrome in
      extremity trauma and surgery--systematic review and meta-analysis.
AB  - Complex regional pain syndrome (CRPS) is a devastating condition often seen after
      foot and ankle injury and surgery. Prevention of this pathology is attractive not
      only to patients but also to surgeons, because the treatment of this condition
      can be difficult. We evaluated the effectiveness of vitamin C in preventing
      occurrence of CRPS in extremity trauma and surgery by systematically reviewing
      relevant studies. The databases used for this review included: Ovid EMBASE, Ovid
      MEDLINE, CINAHL, and the Cochrane Database. We searched for comparative studies
      that evaluated the efficacy of more than 500 mg of daily vitamin C. After
      screening for inclusion and exclusion criteria, we identified 4 studies that were
      relevant to our study question. Only 1 of these 4 studies was on foot and ankle
      surgery; the rest concerned the upper extremities. All 4 studies were in favor of
      this intervention with minimal heterogeneity (Tau(2) = 0.00). Our quantitative
      synthesis showed a relative risk of 0.22 (95% confidence interval = 0.12, 0.39)
      when daily vitamin C of at least 500 mg was initiated immediately after the
      extremity surgery or injury and continued for 45 to 50 days. A routine, daily
      administration of vitamin C may be beneficial in foot and ankle surgery or injury
      to avoid CRPS. Further foot and ankle specific and dose-response studies are
      warranted.

PMID- 22985496
TI  - OMG: Open Molecule Generator.
AB  - Computer Assisted Structure Elucidation has been used for decades to discover
      the chemical structure of unknown compounds. In this work we introduce the first
      open source structure generator, Open Molecule Generator (OMG), which for a given
      elemental composition produces all non-isomorphic chemical structures that match
      that elemental composition. Furthermore, this structure generator can accept as
      additional input one or multiple non-overlapping prescribed substructures to
      drastically reduce the number of possible chemical structures. Being open source
      allows for customization and future extension of its functionality. OMG relies on
      a modified version of the Canonical Augmentation Path, which grows intermediate
      chemical structures by adding bonds and checks that at each step only unique
      molecules are produced. In order to benchmark the tool, we generated chemical
      structures for the elemental formulas and substructures of different metabolites
      and compared the results with a commercially available structure generator. The
      results obtained, i.e. the number of molecules generated, were identical for
      elemental compositions having only C, O and H. For elemental compositions
      containing C, O, H, N, P and S, OMG produces all the chemically valid molecules
      while the other generator produces more, yet chemically impossible, molecules.
      The chemical completeness of the OMG results comes at the expense of being slower
      than the commercial generator. In addition to being open source, OMG clearly
      showed the added value of constraining the solution space by using multiple
      prescribed substructures as input. We expect this structure generator to be
      useful in many fields, but to be especially of great importance for metabolomics,
      where identifying unknown metabolites is still a major bottleneck.

PMID- 22985497
TI  - Ketamine potentiates hippocampal neurodegeneration and persistent learning and
      memory impairment through the PKCgamma-ERK signaling pathway in the developing
      brain.
AB  - Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a
      general pediatric anesthetic. Recent studies suggest that ketamine enhances
      neuronal apoptosis in developing rodents and nonhuman primates. The main goal of
      this study is to determine whether ketamine causes hippocampal neurodegeneration
      and behavioral deficits in adulthood, and if so, whether the effects of ketamine
      are associated with protein kinase C-gamma (PKCgamma), extracellular signal
      regulated kinase (ERK)1/2 and Bcl-2 expression. Starting from postnatal day 7,
      Sprague-Dawley rat pups randomly received daily ketamine treatment (25, 50 and
      75mg/kg, ip) for three consecutive days. Twenty-four hours after the last
      treatment with ketamine, the rats were decapitated, and the hippocampi were
      isolated for detection of neuronal apoptosis by TUNEL. The protein expression
      levels of PKCgamma, ERK1/2 and Bcl-2 in the hippocampi were measured by western
      blot analysis. At 2months of age, learning and memory abilities were tested by
      the Morris water maze. Ketamine increased the number of apoptotic cells in the
      CA1 region and dentate gyrus at a dose of 75mg/kg but not at lower doses of 25
      and 50mg/kg. The dose of 75mg/kg of ketamine suppressed p-PKCgamma, p-ERK1/2 and
      Bcl-2 expression but not t-PKCgamma or t-ERK expression. Ketamine administered to
      the developing brains of P7 rats at a dose of 75mg/kg caused learning and memory
      impairments in adulthood. Therefore, these data demonstrate that ketamine at a
      dose of 75mg/kg in the developing brain results in hippocampal neurodegeneration
      and persistent learning and memory impairment, which is associated with the
      PKCgamma-ERK signaling pathway. This article is part of a Special Issue entitled:
      Brain Integration.

PMID- 22985498
TI  - Acute effects of neonatal dexamethasone treatment on proliferation and astrocyte
      immunoreactivity in hippocampus and corpus callosum: towards a rescue strategy.
AB  - Dexamethasone (DEX), a synthetic glucocorticoid, has been used to treat
      respiratory distress syndrome in prematurely born infants. Despite the important
      short-term benefit on lung function, there is growing concern about the long-term
      outcome of this treatment, since follow-up studies of prematurely born infants
      have shown lasting adverse neurodevelopmental effects. Since the mechanism
      underlying these neurodevelopmental impairments is largely unknown, the aim of
      the present study was (i) to investigate the acute effects of neonatal DEX
      treatment on the developing brain; and (ii) to block specifically the effects of
      DEX on the brain by central administration of the glucocorticoid receptor (GR)
      antagonist mifepristone. Long Evans rat pups were injected subcutaneously with
      tapering doses of DEX or saline (SAL) on postnatal days (pnd) 1, 2 and 3.
      Separate groups received intracerebroventricular injections with mifepristone
      prior to DEX treatment. On pnd 4 and 10, pups were sacrificed and brains
      collected for analysis of cell proliferation (Ki-67) and astrogliosis (GFAP). We
      report that neonatal DEX treatment reduced hippocampal cell proliferation on pnd
      4, an effect that was normalized by pnd 10. Although on pnd 4, GFAP expression
      was not affected, DEX treatment caused a significant reduction in the number and
      density of astrocytes in hippocampus and corpus callosum on pnd 10, which was
      normalized by mifepristone pre-treatment. These acute alterations in the neonate
      brain might underlie later functional impairments reported in DEX-treated animals
      and humans and further illustrate the impact of early GR activation on brain
      development.

PMID- 22985499
TI  - Binding of bivalent ions to actinomycete mannanase is accompanied by
      conformational change and is a key factor in its thermal stability.
AB  - The study aimed to define the key factors involved in the modulation of
      actinomycete mannanases. We focused on the roles of carbohydrate-binding modules
      (CBMs) and bivalent ions. To investigate the effects of these factors, two
      actinomycete mannanase genes were cloned from Streptomyces thermoluteus (StManII)
      and Streptomyces lividans (SlMan). CBMs fused to mannanase catalytic domains do
      not affect the thermal stability of the proteins. CBM2 of StManII increased the
      catalytic efficiency toward soluble-mannan and insoluble-mannan by 25%-36%, and
      CBM10 of SlMan increased the catalytic efficiency toward soluble-mannan by 40%
      50%. Thermal stability of wild-type and mutant enzymes was enhanced by calcium
      and manganese. Thermal stability of SlMandC was also slightly enhanced by
      magnesium. These results indicated that bivalent ion-binding site responsible for
      thermal stability was in the catalytic domains. Thermal stability of mannanase
      differed in the kinds of bivalent ions. Isothermal titration calorimetry revealed
      that the catalytic domain of StManII bound bivalent ions with a K(a) of 5.39+/
      0.45*10(3)-7.56+/-1.47*10(3)M(-1), and the catalytic domain of SlMan bound
      bivalent ions with a K(a) of 1.06+/-0.34*10(3)-3.86+/-0.94*10(3)M(-1). The
      stoichiometry of these bindings was consistent with one bivalent ion-binding site
      per molecule of enzyme. Circular dichroism spectrum revealed that the presence of
      bivalent ions induced changes in the secondary structures of the enzymes. The
      binding of certain bivalent ion responsible for thermal stability was accompanied
      by a different conformational change by each bivalent ion. Actinomycete
      mannanases belong to GHF5 which contained various hemicellulases; therefore, the
      information obtained from mannanases applies to the other enzymes.

PMID- 22985500
TI  - Outcomes of trophectoderm biopsy on cryopreserved blastocysts: a case series.
AB  - Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF.
      The information gained from PGD may be used to reduce the incidence of
      chromosomally abnormal pregnancies and augment the current selection process of
      embryos. As such, patients may choose to utilize PGD in either fresh or
      cryopreserved IVF cycles. It is a common practice to cryopreserve excess embryos
      at the blastocyst stage. In these cases, trophectoderm biopsy is the only
      technique available for PGD. This articles reports this study centre's experience
      with trophectoderm biopsies of cryopreserved blastocysts in 12 patients who
      underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46%
      and the ongoing pregnancy rate per embryo transfer was 63%. The results from this
      case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to
      perform PGD is logistically feasible. In addition, the rate of implantation and
      ongoing pregnancy were maintained within a reasonable range to justify the
      procedure. Preimplantation genetic diagnosis (PGD) is an increasingly common
      adjunct to IVF and is used to evaluate the genetic makeup of the embryo prior to
      transfer of the embryo into the uterus. The information gained from PGD may be
      used to identify single-gene disorders that result in genetic disease, reduce the
      incidence of chromosomally abnormal pregnancies and/or augment the selection
      process of embryos to be transferred. In order to perform PGD, a biopsy of the
      embryo is the performed and cells are removed for testing. PGD may be performed
      in either fresh or frozen (cryopreserved) IVF cycles. Patients who have
      cryopreserved embryos remaining in storage from a previous fresh cycle may wish
      to have these embryos tested with PGD. Many embryos are frozen on day 5 of
      development, referred to as the blastocyst stage. At this stage of development,
      embryo biopsy is performed via a technique known as 'trophectoderm biopsy', in
      which 1-3 of the cells destined to become the placenta are removed from the
      embryo for chromosomal testing. We report our experience with trophectoderm
      biopsy of frozen blastocysts in 12 patients who underwent 13 cycles of PGD. The
      implantation rate per embryo transferred was 46% and the ongoing pregnancy rate
      per embryo transfer was 63%. The results from this case series demonstrate that
      trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically
      feasible. In addition, the rate of implantation and ongoing pregnancy were
      maintained within a reasonable range to justify the procedure.

PMID- 22985501
TI  - Quantifying and assessing the effect of chemical symmetry in metabolic pathways.
AB  - Atom tracing provides valuable information in many analyses of metabolic networks
      including pathway inference and flux estimation. Symmetries-mapping operations
      that produce atom equivalencies-introduce alternative tracings when multiple atom
      mappings are aggregated. Although several attempts have been made to consider
      symmetry while curating atom mappings, a definition of the symmetry amenable to
      automated computation and a systematic quantification of the extent of symmetries
      in both compounds and reactions is still lacking. Moreover, the impact of
      symmetries on the calculation of the atom economy of pathways and the simulation
      of isotopomer distribution is yet to be assessed. In this study, we formulate the
      symmetries of both compounds and reactions as automorphic mappings of the
      corresponding graph representations. We investigate the extent of both compound
      and reaction symmetries in several metabolic systems. We find, through random
      walking in the metabolic network of E.coli , that alternative tracings originated
      from symmetries could give rise to considerable amount of differential
      conservation of atoms and distinct transition patterns of the isotopomer
      distribution.

PMID- 22985502
TI  - Narrow band imaging diagnosis of bladder cancer: systematic review and meta
      analysis.
AB  - What's known on the subject? and What does the study add? In recent years, more
      attention has focused on the role of narrow band imaging (NBI) in bladder cancer
      detection and NBI technology has spread rapidly. It is an important method for
      diagnosing new or recurrent bladder cancer. But its diagnostic accuracy is still
      uncertain. This paper summarizes the diagnostic accuracy of NBI in bladder cancer
      and compares NBI with white light imaging. The results show that NBI cystoscopy
      significantly improves the detection accuracy in bladder cancer, compared with
      white light imaging. However, some limitations still exist. Multicentre
      randomized studies are recommended to determine whether the visual advantages of
      NBI can translate into real therapeutic benefit for individual patients.
      OBJECTIVE: * To assess the test performance and clinical effectiveness of narrow
      band imaging (NBI) cystoscopy compared with white light imaging (WLI) cystoscopy
      in people suspected of new or recurrent bladder cancer. METHODS: * Literature on
      NBI cystoscopy in the diagnosis of bladder cancer was searched in PubMed, EMBASE,
      Cochrane Library, MEDLINE and CNKI, with hand searching of relevant congress
      abstracts and journals. * The literature was selected according to inclusion and
      exclusion criteria. The Meta-DiSc1.4 software was used to review management and
      analysis. RESULTS: * Eight studies including 1022 patients assessed test
      performance. * On a per-person analysis, the pooled sensitivity, specificity,
      positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of
      NBI and WLI were respectively 0.943 (95% CI 0.914-0.964) and 0.848 (95% CI 0.803
      0.885), 0.847 (95% CI 0.812-0.878) and 0.870 (95% CI 0.831-0.903), 7.038 (95% CI
      3.357-14.754) and 6.938 (95% CI 2.052-23.465), 0.054 (95% CI 0.012-0.237) and
      0.181 (95% CI 0.091-0.361), and 185.32 (95% CI 45.714-751.26) and 42.931 (95% CI
      8.088-227.88). * The area under the curve and Q* of NBI and WLI were respectively
      0.9781 and 0.8944, and 0.9337 and 0.8253. * For the characterization of carcinoma
      in situ, the pooled sensitivity, specificity, positive likelihood ratio, negative
      likelihood ratio and diagnostic odds ratio of NBI were 0.927 (95% CI 0.878
      0.960), 0.768 (95% CI 0.730-0.802), 4.545 (95% CI 2.820-7.325), 0.125 (95% CI
      0.051-0.304) and 48.884 (95% CI 15.642-152.77) on a per-person analysis. * The
      area under the curve and Q* were 0.9391 and 0.8763. CONCLUSION: * NBI is an
      effective method for the identification of abnormal lesions including carcinoma
      in situ and can provide higher diagnostic precision of bladder cancer than WLI.

PMID- 22985504
TI  - Occludin dislocation in brain capillary endothelium of rats with bile duct
      ligation induced cholestasis.
AB  - The present study used a rat model with bile duct ligation to examine the effect
      of cholestasis, to the localization of occludin in brain capillary endothelium by
      means of electronic microscopy. The results demonstrated a dislocation of
      occludin away from the tight junction sites of brain endothelial cells. A
      significant increase of the occludin-interendothelial cleft distance was
      demonstrated in the midbrain and the cerebellum samples but not in the frontal
      cortex, compared to the control group samples. These findings imply a brain
      region selective derangement of occludin in response to liver disease.

PMID- 22985503
TI  - Sf-PHB2, a new transcription factor, drives WSSV Ie1 gene expression via a 12-bp
      DNA element.
AB  - BACKGROUND: The WSSV immediate early gene ie1 is highly expressed throughout
      viral infection cycle and may play a central role in initiating viral replication
      during infection. RESULTS: Here, a detailed characterization of the ie1 promoter
      was performed using deletion and mutation analyses to elucidate the role of the
      individual promoter motifs. Three results were obtained: 1) the ie1 promoter is a
      classical eukaryotic promoter that contains the initiator element (Inr) and TATA
      box responsible for the basal promoter activity; 2) mutation or truncation of a
      predicted Sp1 site decreased the level of promoter activity by about 3-fold,
      indicating that the Sp1 site is an important cis-element of the promoter; and 3)
      truncation of a 12-bp sequence that resides at -78/-67 of the ie1 promoter
      decreased the level of promoter activity by about 14-fold, indicating that the 12
      bp motif is a critical upstream element of the ie1 promoter for binding of a
      strong transcription factor to drive the ie1 gene expression in the cells.
      Further, the 12-bp DNA binding protein was purified from the nuclear proteins of
      Sf9 cells using DNA affinity chromatography, and was identified as a homologue of
      the prohibitin2 protein (named as Sf-PHB2) using mass spectrometry. Furthermore,
      the DNA binding activity of Sf-PHB2 was verified using a super shift analysis.
      CONCLUSION: These results support that the Sf-PHB2 is a novel transcription
      factor that drives WSSV ie1 gene expression by binding to the 12-bp DNA element.

PMID- 22985505
TI  - A comparative study of the effects of ABT-418 and methylphenidate on spatial
      memory in an animal model of ADHD.
AB  - Impaired learning performance in scholastic settings is a characteristic of
      attention deficit hyperactivity disorder (ADHD). Our present study compares the
      effect of a nicotinic acetylcholine receptor (nAChR) agonist, ABT-418, and
      methylphenidate (MPH) on spatial memory in spontaneously hypertensive rats
      (SHRs), an animal model of ADHD. Neither chronic administration of ABT-418 nor
      MPH affected the learning performance during training in the Morris water maze.
      However, both compounds significantly improved memory. SHRs treated with a
      combination of the compounds did not perform better than either drug alone.
      Furthermore, the cortical alpha4 and beta2 nAChR subunits and the hippocampal
      alpha4 subunit expression were significantly enhanced by ABT-418 treatments.
      Collectively, these results suggest that ABT-418 effectively improved spatial
      memory in an animal model of ADHD, providing a theoretical foundation for the use
      of a nAChR agonist in ADHD treatment.

PMID- 22985506
TI  - Spinocerebellar ataxia type 23 is an uncommon SCA subtype in the Chinese Han
      population.
AB  - The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous
      group of neurodegenerative diseases. In 2010, four missense mutations in the
      prodynorphin (PDYN) gene were found in two families and two sporadic cases of SCA
      type 23 (SCA23) from the Netherlands. In addition, one missense mutation in PDYN
      was also found in one sporadic SCA23 case in America in 2012. To date, there have
      been no reports of PDYN gene mutations in mainland China. To investigate the
      frequency of SCA23 among the Chinese Han population, we performed polymerase
      chain reaction (PCR) and DNA direct sequencing of the PDYN gene in 305 unrelated
      ataxia patients. Although no SCA23 mutation was identified, one novel single
      nucleotide polymorphism (c.255G>A, p.Lys85Lys) in exon 4 of the PDYN gene was
      found. This suggests that SCA23 is a rare form of dominant ataxia in the Chinese
      Han population.

PMID- 22985507
TI  - Spinal blockades of class I antiarrythmic drugs with bupivacaine by
      isobolographic analysis in rats.
AB  - Flecainide, quinidine, and mexiletine have been shown to be sodium channel
      blockers and local anesthetics. The purpose of this study was to examine the
      interaction of the traditional local anesthetic bupivacaine with flecainide,
      quinidine, or mexiletine on spinal blockades. To obtain the 50% effective dose
      (ED(50)) of drugs, dose-dependent responses of spinal blockades of motor and
      sensory functions with intrathecal flecainide, quinidine, mexiletine, and
      bupivacaine in rats were constructed. Using a continuum of different fixed drug
      dose ratios, the interactions of bupivacaine with drugs (flecainide, quinidine,
      or mexiletine) were evaluated by an isobolographic analysis. Our resulting data
      showed that flecainide, quinidine, and mexiletine, as well as local anesthetic
      bupivacaine produced dose-dependent spinal blockades in motor function and
      nociception. Flecainide had the most potent spinal antinociceptive effect
      (P<0.01) among these three class I antiarrhythmic drugs. Co-administration of
      bupivacaine with flecainide, quinidine, or mexiletine displayed an additive
      effect on spinal blockades of motor function and nociception. We concluded that
      bupivacaine combined with flecainide, quinidine, or mexiletine exhibited an
      additive effect on spinal blockades of motor function and nociception. Using such
      a combination strategy to produce antinociception may potentially provide an
      improved therapeutic separation from myocardial toxicity occurred after spinal
      bupivacaine.

PMID- 22985508
TI  - Risperidone attenuates the increase of extracellular nitric oxide and glutamate
      levels in serotonin syndrome animal models.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) syndrome is a potentially life-threatening
      neurotoxic condition provoked by pharmacologically induced excess serotonergic
      activity. Several studies report that nitric oxide (NO) and glutamate play a role
      in psychostimulant-induced hyperthermia related to neurotoxicity. In the present
      study, the involvement of NO and glutamate, as well as the effect of risperidone,
      a potent 5-HT(2A) and D(2) (and a less potent D(1)) receptor antagonist, were
      investigated in animal models of 5-HT syndrome. Two 5-HT syndrome animal models
      were utilized. The first model was induced by administration of tranylcypromine,
      a nonselective monoamine oxidase (MAO) inhibitor, and fluoxetine, a selective 5
      HT reuptake inhibitor. The second model was induced by the administration of
      clorgyline, an MAO-A inhibitor, and 5-hydroxy-l-tryptophan, a precursor of 5-HT.
      Changes in the level of NO metabolites and glutamate in the anterior hypothalamus
      were measured using microdialysis. In both models, NO metabolite levels
      significantly increased, and this increase was significantly attenuated by
      risperidone pretreatment. Extracellular levels of glutamate were increased only
      in the tranylcypromine and fluoxetine model, and this increase was significantly
      attenuated by risperidone pretreatment. These results indicate that NO and
      glutamate may be involved in the development of 5-HT syndrome and that
      risperidone may be effective against neurotransmitter abnormalities in 5-HT
      syndrome.

PMID- 22985509
TI  - Effects of the active constituents of Crocus Sativus L., crocins, in an animal
      model of obsessive-compulsive disorder.
AB  - Crocins are among the active components of the plant Crocus Sativus L. C. Sativus
      L. and its constituents were effective in different models of psychiatric
      disorders including anxiety and depression. Obsessive-compulsive disorder (OCD)
      is a common psychiatric disorder defined by the presence of obsessive thoughts
      and repetitive compulsive actions. The non selective serotonin (5-HT) receptor
      agonist mCPP is known to induce OCD-like behavior (excessive self-grooming) in
      rodents and exacerbate symptoms in patients with OCD. The present study
      investigated whether or not crocins were able to counteract excessive self
      grooming induced by mCPP (0.6 mg/kg, i.p.) in rats. Crocins (30 and 50mg/kg,
      i.p.) attenuated mCPP-induced excessive self-grooming. The present results also
      indicate that these effects of crocins on an animal model of OCD cannot be
      attributed to changes in locomotor activity. Our findings suggest that the active
      constituents of C. Sativus L. crocins might play a role in compulsive behavior
      and support a functional interaction between crocins and the serotonergic system.

PMID- 22985510
TI  - Loss of short-latency afferent inhibition and emergence of afferent facilitation
      following neuromuscular electrical stimulation.
AB  - Neuromuscular electrical stimulation (NMES) increases the excitability of
      corticospinal (CS) pathways by altering circuits in motor cortex (M1). How NMES
      affects circuits interposed between the ascending afferent volley and descending
      CS pathways is not known. Presently, we hypothesized that short-latency afferent
      inhibition (SAI) would be reduced and afferent facilitation (AF) enhanced when
      NMES increased CS excitability. NMES was delivered for 40 min over the ulnar
      nerve. To assess CS excitability, motor evoked potentials (MEPs) were evoked
      using transcranial magnetic stimulation (TMS) delivered at 120% resting threshold
      for first dorsal interosseus muscle. These MEPs increased by ~1.7-fold following
      NMES, demonstrating enhanced CS excitability. SAI and AF were tested by
      delivering a "conditioning" electrical stimulus to the ulnar nerve 18-25 ms and
      28-35 ms before a "test" TMS pulse, respectively. Conditioned MEPs were compared
      to unconditioned MEPs evoked in the same trials. TMS was adjusted so
      unconditioned MEPs were not different before and after NMES. At the SAI interval,
      conditioned MEPs were 25% smaller than unconditioned MEPs before NMES but
      conditioned and unconditioned MEPs were not different following NMES. At the AF
      interval, conditioned MEPs were not different from unconditioned MEPs before
      NMES, but were facilitated by 33% following NMES. Thus, when NMES increases CS
      excitability there are concurrent changes in the effect of afferent input on M1
      excitability, resulting in a net increase in the excitatory effect of the
      ascending afferent volley on CS circuits. Maximising this excitatory effect on M1
      circuits may help strengthen CS pathways and improve functional outcomes of NMES
      based rehabilitation programs.

PMID- 22985511
TI  - Effect of saikosaponin A on maintenance of intravenous morphine self
      administration.
AB  - In this study, we investigated the effects of saikosaponin A (SSA), a major
      compound of Bupleurum falcatum L., on morphine self-administration behavior. Male
      Sprague-Dawley rats were trained to self-administer intravenous morphine
      (0.1mg/kg per injection over 5s) during daily 1-h sessions under a fixed-ratio 1
      schedule. Rats were pretreated with SSA (0.25, 0.5, 1.0mg/kg) by intraperitoneal
      injection 30 min prior to the start of the test session. Results demonstrated
      that pretreatment with SSA reduced morphine-maintained responding dose
      dependently. Additionally, SSA inhibition of morphine-reinforced behavior was
      blocked by the selective GABA(B) receptor antagonist (2S)(+)-5,5-dimethyl-2
      morpholineacetic acid (SCH 50911), but not the selective GABA(A) receptor
      antagonist bicuculline. Together, these results suggest that SSA may effectively
      suppress morphine-reinforced behavior by activating GABA(B) receptors.

PMID- 22985512
TI  - Inhibition of peroxisomal beta-oxidation by thioridazine increases the amount of
      VLCFAs and Abeta generation in the rat brain.
AB  - Alzheimer's disease (AD) is characterized by the accumulation of the beta-amyloid
      peptide (Abeta), which is generated from sequential cleavages of the amyloid
      precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase. Fatty acid
      alterations in AD brains have recently received substantial attention. Because
      increased very long chain fatty acid (VLCFA) levels in AD brains imply that
      peroxisomal beta-oxidation dysfunction may be associated with AD pathogenesis, we
      investigated the effects of impaired peroxisomal beta-oxidation on Abeta
      generation in vivo and in vitro using thioridazine, a selective peroxisomal beta
      oxidation inhibitor. Under the experimental conditions, thioridazine caused VLCFA
      accumulation and increases in Abeta(40) content, APP immunoreactivity and
      APP(751+770) mRNA expressions in the rat cerebral cortex. A correlation analysis
      showed that the Abeta(40) levels were positively correlated with the cortex
      C(24:0) and C(26:0) levels. Additionally, the primary cerebral cortex neurons
      treated with this compound showed increases in APP(751+770) mRNA, APP protein,
      BACE1 mRNA and protein, and secreted Abeta40 levels. This work supports an
      emerging viewpoint that impaired peroxisomal function may play an important role
      in the progression of AD pathology.

PMID- 22985513
TI  - Mental fatigue impairs pre-attentive processing: a MMN study.
AB  - Individuals frequently experience mental fatigue during or after prolonged
      periods of cognitive activity. We investigated the effects of mental fatigue on
      the ability to detect minor changes in the pre-attentive stage of information
      processing by recoding MMN of ERP components. The equal probable paradigm was
      employed to elicit pure memory-comparison-based MMN component. Mental fatigue was
      induced by the continuous performance for 2h of mental arithmetic tasks. MMN
      amplitudes at fronto-central electrode sites were significantly decreased in
      subjects with mental fatigue than in subjects under control conditions, whereas
      temporal MMN was not affected by mental fatigue. These results suggest that
      mental fatigue impairs pre-attentive processing.

PMID- 22985515
TI  - Quercetin protects neuroblastoma SH-SY5Y cells against oxidative stress by
      inhibiting expression of Kruppel-like factor 4.
AB  - Quercetin is one of flavonoids with cyto-protective activities. It has been
      demonstrated that quercetin inhibits oxidative stress in some animal models and
      specific cells, but the particular mechanism is known a little. In the present
      study, we found that quercetin could decrease the expression of Kruppel-like
      factor 4 (KLF4) induced by hydrogen peroxide (H(2)O(2)) in human neuroblastoma SH
      SY5Y cells, further increase the expression ratio of bcl-2 to bax, which were
      apoptotic-related target genes of KLF4, thus alleviate the apoptotic rate and
      caspase-3 enzyme activity of SH-5YSY cells; the overexpression or inhibition of
      KLF4 demonstrated the mediated role of KLF4 for the protective effect of
      quercetin on cell damage induced by H(2)O(2). All results suggest a potential
      molecular mechanism of quercetin protecting against the oxidative damage, which
      may be applied in the treatment of oxidative related diseases, such as
      neurodegeneration diseases.

PMID- 22985514
TI  - TGF-beta induced by interleukin-34-stimulated microglia regulates microglial
      proliferation and attenuates oligomeric amyloid beta neurotoxicity.
AB  - Microglia play critical roles in the pathogenesis of Alzheimer's disease (AD). We
      have previously shown that interleukin-34 (IL-34) enhances microglial
      proliferation and induces microglial neuroprotective properties against
      oligomeric amyloid beta (oAbeta) toxicity by producing insulin degrading enzyme,
      an Abeta degrading enzyme, and anti-oxidant enzyme heme oxygenase-1. In this
      study, we found that IL-34 dose-dependently induces TGF-beta in microglia, and
      that TGF-beta attenuates oAbeta neurotoxicity in neuron microglial co-cultures.
      The TGF-beta 1 receptor kinase inhibitor SD208 enhances microglial proliferation
      by IL-34 and suppresses the neuroprotective effect of IL-34-treated microglia.
      These findings suggest that TGF-beta produced by IL-34-treated microglia is a
      negative regulator of microglial proliferation and enhances the neuroprotective
      property of microglia.

PMID- 22985516
TI  - Fractone-heparan sulfates mediate BMP-7 inhibition of cell proliferation in the
      adult subventricular zone.
AB  - Bone morphogenetic protein-7 (BMP-7) is a heparin-binding growth factor that
      inhibits cell proliferation in the subventricular zone (SVZ) of the lateral
      ventricle, the primary neurogenic niche in the adult brain. However, the
      physiological mechanisms regulating the activity of BMP-7 in the SVZ are unknown.
      Here, we report the inhibitory effect of BMP-7 on cell proliferation through the
      anterior SVZ after intracerebroventricular injection in the adult mouse. To
      determine whether the inhibition of cell proliferation induced by BMP-7 is
      dependant on heparin-binding, heparitinase-1 was intracerebroventricularly
      injected to N-desulfate heparan sulfate proteoglycans before BMP-7 was injected.
      Heparatinase-1 drastically reduced the inhibitory effect of BMP-7 on cell
      proliferation in the SVZ. To determine where BMP-7 binds within the niche, we
      visualized biotinylated-BMP-7 after intracerebroventricular injection, using
      streptavidin Texas red on frozen brain sections. BMP-7 binding was seen as puncta
      in the SVZ at the location of fractones, the particulate specialized
      extracellular matrix of the SVZ, which have been identified primarily by N
      sulfated heparan sulfate immunoreactivity (NS-HS+). BMP binding was also seen in
      NS-HS+ blood vessels of the SVZ. Injection of heparitinase-1 prior to
      biotinylated BMP-7 resulted in the absence of signal for biotinylated-BMP-7 in
      the fractones and blood vessels, indicating that the binding is heparan sulfate
      dependant. These results indicate that BMP-7 requires heparan sulfates to bind
      and inhibit cell proliferation in the SVZ neurogenic niche. Heparan sulfates
      concentrated in fractones and SVZ blood vessels emerge as a functional stem cell
      niche component involved in growth factor activity.

PMID- 22985517
TI  - The effects of nicotine on nitric oxide induced anxiogenic-like behaviors in the
      dorsal hippocampus.
AB  - Nicotine, an active tobacco derived alkaloid, regulates the activity of the
      neuronal nitric oxide synthase (nNOS) as well as the release of nitric oxide (NO)
      in the nervous system. Nicotinic acetylcholine receptors and nNOS are abundantly
      co-expressed in the hippocampal neurons and are found to alter anxiety-like
      behaviors in rodents. Dorsal hippocampus may be a site for modulation of anxiety.
      Therefore, in this study, we investigated the possible interactions between
      nicotine and NO systems of the dorsal hippocampus and the resultant effect on
      anxiety-like behaviors. The elevated plus-maze (EPM) test has been used to test
      the anxiety. Intraperitoneal administration of nicotine (0.5mg/kg) decreased the
      open arm time percentage (%OAT) and open arm entries percentage (%OAE) but not
      the locomotor activity, indicating an anxiogenic-like response. Intra-CA1
      injection of l-arginine (a NO precursor) or l-NAME (a NOS inhibitor) also caused
      anxiogenic-like effects. On the other hand, injection of the low dose nicotine
      before different doses of l-arginine or l-NAME blocked the anxiogenic-like
      response induced by the drugs. Our results suggested that, both NO and nicotinic
      cholinergic systems not only play a part in the modulation of the anxiety in mice
      dorsal hippocampus, but also demonstrate a complex interaction in this respect.

PMID- 22985518
TI  - Heptamethoxyflavone, a citrus flavonoid, enhances brain-derived neurotrophic
      factor production and neurogenesis in the hippocampus following cerebral global
      ischemia in mice.
AB  - In the present study using a transient global ischemia mouse model, we showed
      that (1) a citrus flavonoid 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) induced the
      phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and cAMP
      response element-binding protein (CREB) in the hippocampus after ischemia; (2)
      HMF increased the expression of brain-derived neurotrophic factor (BDNF), a
      representative neurotrophic factor in the central nervous system, in the
      hippocampal dentate gyrus, and most BDNF-positive cells were also stained with
      anti-glial fibrillary acidic protein (one of the major intermediate filament
      proteins of mature astrocytes) and (3) HMF increased doublecortin positive
      neuronal precursor cells in the dentate gyrus subventricular zone or subgranular
      zone. These results suggest that HMF has the ability to induce BDNF production in
      astrocytes and enhance neurogenesis after brain ischemia, which may be mediated
      by activation of ERK1/2 and CREB.

PMID- 22985519
TI  - Hyper-phosphorylation of GSK-3beta: possible roles in chlorpyrifos-induced
      behavioral alterations in animal model of depression.
AB  - In recent years, the widespread use of chlorpyrifos (CPF) has aroused concerns
      regarding its potential neurotoxic effects, especially in developing individuals.
      One of the major consequences of CPF exposure is mood disorders such as
      depression. Epidemiological studies have demonstrated susceptibility to
      depression in populations with a history of CPF exposure. Our previous study
      indicated that repeated CPF exposure in doses from 10 to 160 mg/kg elicits
      depression- and anxiety-like alterations. However, whether this alteration is due
      to persistent inhibition of acetylcholinesterase (AChE) was not determined. In
      this study, we used lower doses of CPF to avoid evident inhibition of AChE to
      investigate other potential target systems that contribute to CPF's neurotoxic
      effect. Four-week-old adolescent male rats were repeatedly exposed to CPF at
      doses of 2.5, 5, or 10mg/kg (s.c., 10 days) and then were subjected to either
      neurobehavioral testing or immunoblot analysis. Depression-like behaviors as
      manifested by increased immobility time was observed in force swimming test,
      while immunoblot analysis revealed a dramatically increased phosphorylation of
      glycogen synthase kinase-3beta (GSK-3beta) in the hippocampus and striatum, with
      no effect on the levels of Wnt2, GSK-3beta, or beta-catenin. These results
      suggest a noncholinergic mechanism, the hyper-phosphorylation of GSK-3beta, which
      may contribute to the cellular neurotoxicity of CPF, thus increasing the
      susceptibility to mood disorders.

PMID- 22985520
TI  - Bilateral temporal cortex transcranial direct current stimulation worsens male
      performance in a multisensory integration task.
AB  - Somatosensory integration is a critical cognitive function for human social
      interaction. Though somatosensory integration has been highly explored in
      cognitive studies; only a few studies have explored focal modulation of cortical
      excitability using a speech perception paradigm. In the current study, we aimed
      to investigate the effects of tDCS applied over the temporal cortex of healthy
      subjects during a go-no-go task in which stimuli were shapes and non-words.
      Twenty-eight subjects were randomized to receive cathodal, anodal or sham tDCS
      bilaterally over the superior temporal cortex (the reference electrode was on
      deltoid) in a counterbalanced order. The effects on judgment of congruency
      between shapes and non-words in healthy volunteers were measured by a go-no-go
      task. Our findings show a significant modification of performance according to
      the polarity of stimulation, task and subject gender. We found that men performed
      worse on the no-go condition for congruent stimuli during cathodal tDCS. For
      reaction time, on the other hand, there was a similar effect for anodal and
      cathodal stimulation. There were significantly faster responses on incongruent
      trials during both anodal and cathodal tDCS. Along with previous literature
      showing gender differences in tasks associated with speech perception, the
      findings of this study provide additional evidence suggesting that men may have a
      more focal and restricted neural processing in this multisensory integration
      task.

PMID- 22985521
TI  - Genetics and pharmacogenomics of diffuse gliomas.
AB  - Rapidly evolving techniques for analysis of the genome provide new opportunities
      for cancer therapy. For diffuse gliomas this has resulted in molecular markers
      with potential for personalized therapy. Some drugs that utilize pharmacogenomics
      are currently being tested in clinical trials. In melanoma, lung-, breast-,
      gastric- and colorectal carcinoma several molecular markers are already being
      clinically implemented for diagnosis and treatment. These insights can serve as a
      background for the promise and limitations that pharmacogenomics has for diffuse
      gliomas. Better molecular characterization of diffuse gliomas, including analysis
      of the molecular underpinnings of drug efficacy in clinical trials, is urgently
      needed. We foresee exciting developments in the upcoming years with clinical
      benefit for the patients.

PMID- 22985522
TI  - Thyroid functions of neonates with Down syndrome.
AB  - BACKGROUND: We aimed to evaluate thyroid functions and volumes and detect
      abnormalities in 80 neonates with Down syndrome. METHODS: Data about free
      triiodothyronine, free thyroxine, thyroid stimulating hormone, thyroglobulin and
      urinary iodine levels, and ultrasonographic thyroid volume were collected.
      RESULTS: Abnormal thyroid function tests were detected in 53.8% of the patients
      (n = 50) and these were hyperthyrotropinemia, hypothyroidism, iodine deficiency
      and iodine overload in 32, 2, 12 and 4 patients, respectively. Thyroid volumes
      were assessed in 36 patients and a total of 17 abnormalities were detected (7
      hypoplasia, 3 agenesis and 7 goiter). In patients with hyperthyrotropinemia mean
      thyroid volume was significantly greater and mean TSH was significantly higher
      when compared to the patients without hyperthyrotropinemia. CONCLUSION: Neonatal
      screening by thyroid function tests in Down syndrome should be performed to
      prevent further intellectual deterioration and improve overall development. In
      the neonatal period, the risk of hyperthyrotropinemia should be kept in mind.

PMID- 22985523
TI  - Ultraviolet irradiation: An effective inactivation method of Aspergillus spp. in
      water for the control of waterborne nosocomial aspergillosis.
AB  - Invasive aspergillosis is the second most common cause of nosocomial fungal
      infections and occurring mainly by Aspergillus fumigatus, Aspergillus flavus, and
      Aspergillus niger. There is evidence that nosocomial aspergillosis may be
      waterborne. This study was conducted to evaluate the ultraviolet (UV) irradiation
      efficiency in terms of inactivating the most important Aspergillus species in
      water since these are potential sources for nosocomial aspergillosis. A
      continuous flow UV reactor which could be used as a point-of-use (POU) system was
      used to survey Aspergillus inactivation by UV irradiation. The inactivation
      efficiency of UV fluence (4.15-25 mJ/cm(2)) was measured by determination of
      fungal density in water before and after radiation. Because turbidity and iron
      concentration are two major water quality factors impacting UV disinfection
      effectiveness, the potential influence of these factors on UV inactivation of
      Aspergillus spp. was also measured. The 4 log inactivation for A. fumigatus, A.
      niger and A. flavus at a density of 1000 cfu/ml was achieved at UV fluences of
      12.45 mJ/cm(2), 16.6 mJ/cm(2) and 20.75 mJ/cm(2), respectively. The inactivation
      efficiency for lower density (100 cfu/ml) was the same as for the higher density
      except for A. flavus. The removal efficiency of Aspergillus spp. was decreased by
      increasing the turbidity and iron concentration. UV disinfection could
      effectively inactivate Aspergillus spores from water and eliminate potential
      exposure of high-risk patients to fungal aerosols by installation of POU UV
      systems.

PMID- 22985524
TI  - A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (alpha) anthracene (DMBA)
      induced micronuclei in mammalian cells in vitro and in vivo.
AB  - Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to
      have both anticarcinogenic and antigenotoxic properties. We evaluated the
      protective effects of CHL (25MUM in vitro, 4 and 100mg/kg. b.w.) on the
      clastogenic action of two model carcinogens, MNNG and DMBA (25MUM and 2MUM
      respectively) in vitro on human hepatoma cells (HepG2) and (40mg and 25mg/Kg/b.w.
      respectively) in vivo on bone marrow of mice, using the frequencies of induced
      micronuclei as the end point. Pre-, post- and simultaneous treatments with CHL
      and the carcinogen were carried out in vitro. With MNNG, only simultaneous
      treatment with CHL was effective in reducing the frequencies of MN, suggesting a
      direct interaction between CHL and MNNG. A statistically significant reduction in
      of DMBA induced MN was found by pre-or post treatment with CHL while a reduction
      (not significant) was observed by simultaneous treatment. In in vivo experiments,
      CHL pre-treatment did not affect the frequencies of MN in PCEs of bone marrow
      induced by MNNG or DMBA. However, increased the toxic effect of DMBA (reduction
      in percent of PCEs) was accompanied by a reduction in the induced frequencies of
      MN. CHL was not clastogenic in both in vitro and in vivo tests. It can be
      concluded that (a) CHL has a protective effect against MNNG and DMBA. This effect
      is dependent upon the protocol employed in in vitro experiments. In vivo, CHL did
      not have a protective effect against MNNG and DMBA. A protective effect of CHL
      against DMBA was evident only at high toxic levels.

PMID- 22985525
TI  - Size-exclusion-chromatography separation of randomly branched polymers with
      tetrafunctional branch points and local dispersity.
AB  - The SEC separation of a randomly branched polymer, in particular local dispersity
      due to branching, are theoretically examined. A model of the SEC separation of
      randomly branched polymer with tetrafunctional branch points enabling the
      estimation of local dispersity was developed. Measurable quantities (branching
      indices) were compared with real data. Local dispersity due to branching is
      demonstrated to depend on elution volume and degree of branching and in the area
      of the beginning of the elution curve it can reach non-negligible values.

PMID- 22985526
TI  - Investigation and optimization of particle dimensions for needle trap device as
      an exhaustive active sampler.
AB  - Various needle trap devices (NTDs) with different designs have been developed
      during the past decade. A theoretical model on the fundamentals of the NTD was
      recently proposed, which employed the theory of frontal (gas-solid)
      chromatography to describe the sampling process. In the current work, different
      types of sorbent particles with different dimensions were packed into the needle
      as the adsorbent. The effects of particle dimensions, which would affect the
      packing density and consequently affect the capacity, the extraction efficiency
      and desorption efficiency of the NTD were experimentally investigated and the
      proposed theory was validated. The results demonstrated that NTDs packed with
      small particles possess higher extraction capacity and efficiency but much higher
      resistances to flow as well. The higher resistance did not necessarily result in
      poor desorption efficiency. The observed relationships among those physical
      parameters provide valuable guidance on how to design a NTD with high performance
      for future applications.

PMID- 22985527
TI  - Graphene-supported zinc oxide solid-phase microextraction coating with enhanced
      selectivity and sensitivity for the determination of sulfur volatiles in Allium
      species.
AB  - A graphene-supported zinc oxide (ZnO) solid-phase microextraction (SPME) fiber
      was prepared via a sol-gel approach. Graphite oxide (GO), with rich oxygen
      containing groups, was selected as the starting material to anchor ZnO on its
      nucleation center. After being deoxidized by hydrazine, the Zn(OH)2/GO coating
      was dehydrated at high temperature to give the ZnO/graphene coating. Sol-gel
      technology could efficiently incorporate ZnO/graphene composites into the sol-gel
      network and provided strong chemical bonding between sol-gel polymeric SPME
      coating and silica fiber surface, which enhanced the durability of the fiber and
      allowed more than 200 replicate extractions. Results indicated that pure ZnO
      coated fiber did not show adsorption selectivity toward sulfur compounds, which
      might because the ZnO nanoparticles were enwrapped in the sol-gel network, and
      the strong coordination action between Zn ion and S ion was therefore blocked.
      The incorporation of graphene into ZnO based sol-gel network greatly enlarged the
      BET surface area from 1.2 m2/g to 169.4 m2/g and further increased the adsorption
      sites. Combining the superior properties of extraordinary surface area of
      graphene and the strong coordination action of ZnO to sulfur compounds, the
      ZnO/graphene SPME fiber showed much higher adsorption affinity to 1-octanethiol
      (enrichment factor, EF, 1087) than other aliphatic compounds without sulfur
      containing groups (EFs<200). Also, it showed higher extraction selectivity and
      sensitivity toward sulfur compounds than commercial polydimethylsiloxane (PDMS)
      and polydimethylsiloxane/divinylbenzene (PDMS/DVB) SPME fibers. Several most
      abundant sulfur volatiles in Chinese chive and garlic sprout were analyzed using
      the ZnO/graphene SPME fiber in combination with gas chromatography-mass
      spectrometry (GC-MS). Their limits of detection were 0.1-0.7 MUg/L. The relative
      standard deviation (RSD) using one fiber ranged from 3.6% to 9.1%. The fiber-to
      fiber reproducibility for three parallel prepared fibers was 4.8-10.8%. The
      contents were in the range of 1.0-46.4 MUg/g with recoveries of 80.1-91.6% for
      four main sulfides in Chinese chive and 17.1-122.6 MUg/g with recoveries of 73.2
      80.6% for three main sulfides in garlic sprout.

PMID- 22985528
TI  - Elucidation of the Phase I and Phase II metabolic pathways of (+/-)-4'
      methylmethcathinone (4-MMC) and (+/-)-4'-(trifluoromethyl)methcathinone (4-TFMMC)
      in rat liver hepatocytes using LC-MS and LC-MS2.
AB  - (+/-)-4'-Methylmethcathinone hydrochloride [(+/-)-mephedrone, 4-MMC] is a
      synthetic "legal high", with a classical cathinone structure similar to
      methcathinone. In this study, the in vitro metabolism of 4-MMC was investigated
      in Sprague-Dawley rat hepatocytes to characterise the associated Phase I and II
      metabolites. 4-MMC was incubated with rat liver hepatocytes, and the reaction
      mixture was analysed on a zwitterionic hydrophilic interaction (ZIC-HILIC) column
      using LC-MS and LC-MS(2). 4-MMC was metabolised, yielding 17 metabolites. These
      metabolites were structurally characterised on the basis of accurate mass
      analyses and LC-MS(2) fragmentation patterns and the major metabolic routes for 4
      MMC determined to be via (i) oxidation of the 4'-methyl group and (ii) reduction
      of the beta-keto moiety. The biotransformation of a modified 4'-trifluoromethyl-
      derivative (4-TFMMC) has also been studied and shows significant differences in
      its metabolism compared to 4-MMC. Key pharmacokinetic parameters for both drugs
      have been calculated [biological half-lives (t(1/2)) for 4-MMC=61.9 min and for 4
      TFMMC=203.8 min] and this data may aid in the understanding of in vivo metabolism
      and the likely pharmacokinetic effects of chemical/structural modifications
      within this class of controlled substances.

PMID- 22985529
TI  - NMR and mass spectrometric characterization of vinblastine, vincristine and some
      new related impurities - part I.
AB  - In the course of exploring the possibilities of developing a new, improved
      process at Gedeon Richter for the production of the "bisindole" alkaloids
      vinblastine (VLB) and vincristine (VCR), some novel VLB/VCR-related trace
      impurities were detected by analytical HPLC. Following isolation by preparative
      HPLC, a combination of 1D and 2D ultra high-field NMR and high-resolution (HR)
      (LC-)MS/MS studies allowed the structural identification and complete spectral
      characterization of several hitherto unpublished VLB/VCR-analogue impurities.
      Since the impurities could not be isolated in entirely pure forms and were
      available only in minute, mass-limited quantities, accessing the spectral
      information needed for their ab initio structure determination was met with
      various practical difficulties. Successful structure determination therefore
      relied heavily on the availability and use of detailed and definitive spectral
      data for both VLB and VCR. In particular, the utilization of detailed (1)H,
      (13)C, and (15)N NMR assignments as well as (1)H-(1)H, (1)H-(13)C and (1)H-(15)N
      spin-spin connectivities pertaining to different solvents for VLB/VCR base and
      sulphate salt was required. Although NMR studies on VLB base and other bisindoles
      were reported earlier in the literature, an NMR characterization of VLB and VCR
      under the above-mentioned circumstances and using ultra-high field
      instrumentation is either scarcely available or entirely lacking, therefore the
      necessary data had to be obtained in-house. Likewise, a modern tandem HR-ESI
      MS/MS(n) fragmentation study of VLB and VCR has not been published yet. In the
      present paper we therefore give a thorough NMR and MS characterization of VLB and
      VCR specifically with a view to filling this void and to provide sufficiently
      extensive and solid reference data for the structural investigation of the
      aforementioned VLB/VCR impurities. Besides being scientifically relevant in its
      own right, the disclosed data should be useful for anyone interested in VLB/VCR
      related molecules at a structural level.

PMID- 22985530
TI  - Correlation between structure, retention, property, and activity of biologically
      relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.
AB  - The physicochemical properties, retention parameters (R(M)(0)), partition
      coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7
      bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to
      reveal the characteristics responsible for their biological behavior. The
      investigated compounds inhibit three unrelated pathogens (the Botulinum
      neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and
      Ebola filovirus) via three different mechanisms of action. To determine the most
      influential factors governing the retention and activities of the investigated
      diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated
      with 2D and 3D molecular descriptors, using a partial least squares regression.
      The resulting quantitative structure-retention (property) relationships indicate
      the importance of descriptors related to the hydrophobicity of the molecules
      (e.g., predicted partition coefficients and hydrophobic surface area).
      Quantitative structure-activity relationship models for describing biological
      activity against the BoNT/A LC and malarial strains also include overall compound
      polarity, electron density distribution, and proton donor/acceptor potential.
      Furthermore, models for Ebola filovirus inhibition are presented qualitatively to
      provide insights into parameters that may contribute to the compounds' antiviral
      activities. Overall, the models form the basis for selecting structural features
      that significantly affect the compound's absorption, distribution, metabolism,
      excretion, and toxicity profiles.

PMID- 22985531
TI  - Computers and neurosurgery.
AB  - At the turn of the twentieth century, the only computational device used in
      neurosurgical procedures was the brain of the surgeon. Today, most neurosurgical
      procedures rely at least in part on the use of a computer to help perform
      surgeries accurately and safely. The techniques that revolutionized neurosurgery
      were mostly developed after the 1950s. Just before that era, the transistor was
      invented in the late 1940s, and the integrated circuit was invented in the late
      1950s. During this time, the first automated, programmable computational machines
      were introduced. The rapid progress in the field of neurosurgery not only
      occurred hand in hand with the development of modern computers, but one also can
      state that modern neurosurgery would not exist without computers. The focus of
      this article is the impact modern computers have had on the practice of
      neurosurgery. Neuroimaging, neuronavigation, and neuromodulation are examples of
      tools in the armamentarium of the modern neurosurgeon that owe each step in their
      evolution to progress made in computer technology. Advances in computer
      technology central to innovations in these fields are highlighted, with
      particular attention to neuroimaging. Developments over the last 10 years in
      areas of sensors and robotics that promise to transform the practice of
      neurosurgery further are discussed. Potential impacts of advances in computers
      related to neurosurgery in developing countries and underserved regions are also
      discussed. As this article illustrates, the computer, with its underlying and
      related technologies, is central to advances in neurosurgery over the last half
      century.

PMID- 22985532
TI  - The rad1 gene in Rainbow Trout (Oncorhynchus mykiss) is highly conserved and may
      express proteins from non-canonical spliced isoforms.
AB  - Cell-cycle checkpoint proteins maintain genomic integrity by sensing damaged DNA
      and initiating DNA repair or apoptosis. RAD1 is a checkpoint protein involved in
      the sensing of damaged DNA and is a part of the 9-1-1 complex. In this project
      rainbow trout rad1 (rtrad1) was cloned, sequenced, expressed as a recombinant
      protein and anti-rtRAD1 antibodies were developed. RAD1 protein levels were
      characterized in various rainbow trout tissues. It was determined that an 840 bp
      open-reading frame encodes 279 aa with a predicted protein size of 31 kDa. The
      rtRAD1 amino-acid sequence is highly conserved and contains conserved exonuclease
      and leucine zipper domains. RT-PCR was used to identify three non-canonical
      splice variants of rtrad1, two of which are capable of forming functional
      proteins. The rad1 splice variant that encodes an 18 kDa protein appears to be
      abundant in rainbow trout spleen, heart and gill tissue and in the RTgill-W1 cell
      line. Based on the genomic rtrad1 sequence the splice variants contain only
      partial exons which are consistent with the splicing of rad1 variants in mammals.
      This is the first time that rad1 has been fully characterized in a fish species.

PMID- 22985533
TI  - Pretransplant iron overload may be associated with increased risk of invasive
      fungal pneumonia (IFP) in patients that underwent allogeneic hematopoietic stem
      cell transplantation (alloHSCT).
AB  - Invasive fungal pneumonia (IFP) has become increasingly common in patients that
      previously underwent alloHSCT. The aim of this study was to determine the role of
      hyperferritinemia, via iron overload in invasive fungal pneumonia in patients
      that underwent alloHSCT. Medical records of 73 patients with pneumonia that
      underwent alloHSCT were studied retrospectively, whereby a pre-transplantation
      serum ferritin level measured up to 100 days prior to transplantation of patients
      with invasive fungal pneumonia (IFP) and non-fungal pneumonia (non-IFP) was
      compared. Patient records revealed 35 and 38 cases of IFP and non-IFP,
      respectively. In risk evaluation for IFP, age, gender, HLA status, conditioning
      regimen, smoking history, and underlying disease were not significantly different
      among groups (p>0.05). However, performance status (Karnofsky) was significantly
      lower in patients with IFP (p<0.05). The median ferritin levels were 1,705 ng/ml
      (41-7198) in the IFP group and 845 ng/ml (18-7099) in non-IFP group and the
      difference was found statistically significant (p=0.001). Elevated pretransplant
      serum ferritin level is associated with IFP in patients that underwent alloHSCT,
      in particular when values exceed 1550 ng/ml.

PMID- 22985534
TI  - Analysis of a questionnaire on adverse reactions to blood donation in Japan.
AB  - In 2007, the Japanese Red Cross Blood Center performed a large-scale
      questionnaire study of post-donation adverse reactions. The questionnaire was
      distributed to 98,389 donors, and the answers were returned by 55,231 (56.1%). In
      total, 2,877 (5.2%) complained of an adverse reaction. Assuming that there were
      no adverse reactions for the 46,150 donors who did not reply, the rate of adverse
      reaction can be speculated to be 2.8%. Our study strongly suggests that blood
      centers have long underestimated the risks of vaso-vagal reactions. Taking at
      least 6h of careful rest after donation would be a helpful counter measure.

PMID- 22985536
TI  - Autoimmune hemolytic anemia due to auto anti-N in a patient with sepsis.
AB  - We describe a case of autoimmune hemolytic anemia (AIHA) due to anti-N in a young
      male patient with cellulitis. There have been several reports of anti-N in N
      positive individuals. But in all these reports, auto anti-N was mostly associated
      with underlying immunological conditions. We report here a case of auto anti-N in
      a patient of bacterial sepsis without any underlying immune disorder.

PMID- 22985535
TI  - The impact of policies to restrict the use of plasma containing products and
      apheresis platelets from female donors to mitigate transfusion related acute lung
      injury (TRALI) in Brazil.
AB  - BACKGROUND AND OBJECTIVES: Although the incidence of TRALI is unknown in Brazil,
      some blood centers have adopted strategies to prevent TRALI. We evaluated the
      impact of three policies to mitigate TRALI on the supply of blood products: to
      divert the production of whole blood-derived plasma from female donors; to defer
      all female donors from apheresis platelet collections, and to defer only
      multiparous female donors from apheresis platelet collections. MATERIALS AND
      METHODS: Data from allogeneic whole blood and apheresis platelet donations from
      April 2008 to December 2009 were collected in three Brazilian blood centers and
      the impact of the aforementioned strategies was evaluated. RESULTS: Of 544,814
      allogeneic blood donations, 30.8% of whole blood plasma and 24.1% of apheresis
      platelet donations would be reduced if only male donor plasma was issued for
      transfusion and all female donors were deferred from apheresis donation,
      respectively. If only multiparous donors were deferred from apheresis donation,
      there would be a 5% decrease of all apheresis platelet collections. CONCLUSION:
      Restricting the use of whole blood derived plasma to male-only donors and
      deferring all female apheresis platelet donors would impact two out of three
      Brazilian blood centers. A deferral policy on multiparous apheresis platelet
      donors may be acceptable as a temporary measure, but may cause more stress on a
      system that is already working at its limit.

PMID- 22985537
TI  - Identification of a support vector machine-based biomarker panel with high
      sensitivity and specificity for nonalcoholic steatohepatitis.
AB  - BACKGROUND: Although liver biopsy remains the best diagnostic standard for
      nonalcoholic steatohepatitis (NASH), non-invasive tests are eagerly awaited. In
      this study, we sought to develop a support vector machine (SVM) algorithm to
      discriminate with high accuracy between subjects with NASH and controls using a
      blood-based biomarker panel. METHODS: A total of 17 biomarkers were measured by
      commercially available enzyme-linked immunosorbent assays in 136 serum samples
      from patients with biopsy-proven NASH (n = 60) and subjects with normal ALT and
      no evidence of fatty liver on ultrasound (n = 76). The database was randomly
      divided (1:1 fashion) into a discovery set for classification training and in a
      validation set of the chosen biomarkers in blinded samples. Multivariate analysis
      was performed by means of SVM. RESULTS: After the identification of a group of
      three most discriminative biomarkers (osteoprotegerin, fibroblast growth factor
      21, and M30) in the discovery set, the application of SVM to the validation test
      resulted in a 92.5% sensitivity and 84.1% specificity for distinguishing subjects
      with NASH from controls. CONCLUSIONS: A targeted biomarker profiling combined
      with a SVM-based pattern identification approach may allow the identification of
      patients with NASH with clinically relevant accuracy and validity.

PMID- 22985538
TI  - Predicted effects of proposed tightened acceptance criterion for Pb proficiency
      testing (PT) on PT sample pass rates for Pb point-of-care testing.
AB  - BACKGROUND: There is current advocacy for change in Pb proficiency testing (PT)
      acceptance criterion from +/- 4 MUg/dl ([Pb] <40 MUg/dl; criterion a) to +/- 2
      MUg/dl ([Pb] <20 MUg/dl, criterion b). We examined the effect of this proposed
      change on PT sample pass rates for point-of-care testing (POCT) as predicted by
      imprecision of POCT PT sample results. METHODS: Inter-site standard deviations
      (s) of POCT PT results were tabulated as a function of [Pb] and characterized as
      a linear function of [Pb] (r(2)>0.8). Given s, predicted minimum, random-error
      only PT failure rates (Fp) as a function of [Pb] were computed as the fraction of
      a normal distribution of results ([Pb]+/- s) that would fall outside of
      boundaries of acceptance criterion a or b. RESULTS: For [Pb]=2-20 MUg/dl, current
      observed PT sample failure rates using criterion a range from 3 to 6%, which are
      greater than the predicted minimum failure rates based on s alone (Fp(a)=0-6%).
      In contrast, predicted minimum failure rates based on s using criterion b are
      greatly increased (Fp(b)=5-35%). CONCLUSIONS: Given the degree of inter-site
      imprecision among POCT Pb PT results, adoption of criterion b for PT acceptance
      will dramatically increase Pb PT sample failure rates for POCT due to random
      error alone.

PMID- 22985539
TI  - Endemic bacteriophages: a cautionary tale for evaluation of bacteriophage therapy
      and other interventions for infection control in animals.
AB  - BACKGROUND: One of the most effective targets for control of zoonotic foodborne
      pathogens in the farm to fork continuum is their elimination in food animals
      destined for market. Phage therapy for Escherichia coli O157:H7 in ruminants, the
      main animal reservoir of this pathogen, is a popular research topic. Since phages
      active against this pathogen may be endemic in host animals and their
      environment, they may emerge during trials of phage therapy or other
      interventions, rendering interpretation of trials problematic. METHODS: During
      separate phage therapy trials, sheep and cattle inoculated with 109 to 1010 CFU
      of E. coli O157:H7 soon began shedding phages dissimilar in plaque morphology to
      the administered therapeutic phages. None of the former was previously identified
      in the animals or in their environment. The dissimilar "rogue" phage was isolated
      and characterized by host range, ultrastructure, and genomic and proteomic
      analyses. RESULTS: The "rogue" phage (Phage vB_EcoS_Rogue1) is distinctly
      different from the administered therapeutic Myoviridae phages, being a member of
      the Siphoviridae (head: 53 nm; striated tail: 152x8 nm). It has a 45.8 kb genome
      which is most closely related to coliphage JK06, a member of the "T1-like
      viruses" isolated in Israel. Detailed bioinformatic analysis reveals that the
      tail of these phages is related to the tail genes of coliphage lambda. The
      presence of "rogue" phages resulting from natural enrichments can pose problems
      in the interpretation of phage therapeutic studies. Similarly, evaluation of any
      interventions for foodborne or other bacterial pathogens in animals may be
      compromised unless tests for such phages are included to identify their presence
      and potential impact.

PMID- 22985540
TI  - The collection of NFATc1-dependent transcripts in the osteoclast includes
      numerous genes non-essential to physiologic bone resorption.
AB  - Osteoclasts are specialized secretory cells of the myeloid lineage important for
      normal skeletal homeostasis as well as pathologic conditions of bone including
      osteoporosis, inflammatory arthritis and cancer metastasis. Differentiation of
      these multinucleated giant cells from precursors is controlled by the cytokine
      RANKL, which through its receptor RANK initiates a signaling cascade culminating
      in the activation of transcriptional regulators which induce the expression of
      the bone degradation machinery. The transcription factor nuclear factor of
      activated T-cells c1 (NFATc1) is the master regulator of this process and in its
      absence osteoclast differentiation is aborted both in vitro and in vivo.
      Differential mRNA expression analysis by microarray is used to identify genes of
      potential physiologic relevance across nearly all biologic systems. We compared
      the gene expression profile of murine wild-type and NFATc1-deficient osteoclast
      precursors stimulated with RANKL and identified that the majority of the known
      genes important for osteoclastic bone resorption require NFATc1 for induction.
      Here, five novel RANKL-induced, NFATc1-dependent transcripts in the osteoclast
      are described: Nhedc2, Rhoc, Serpind1, Adcy3 and Rab38. Despite reasonable
      hypotheses for the importance of these molecules in the bone resorption pathway
      and their dramatic induction during differentiation, the analysis of mice with
      mutations in these genes failed to reveal a function in osteoclast biology.
      Compared to littermate controls, none of these mutants demonstrated a skeletal
      phenotype in vivo or alterations in osteoclast differentiation or function in
      vitro. These data highlight the need for rigorous validation studies to
      complement expression profiling results before functional importance can be
      assigned to highly regulated genes in any biologic process.

PMID- 22985542
TI  - Prosody recognition and audiovisual emotion matching in schizophrenia: the
      contribution of cognition and psychopathology.
AB  - This study aimed to evaluate the ability to decode emotion in the auditory and
      audiovisual modality in a group of patients with schizophrenia, and to explore
      the role of cognition and psychopathology in affecting these emotion recognition
      abilities. Ninety-four outpatients in a stable phase and 51 healthy subjects were
      recruited. Patients were assessed through a psychiatric evaluation and a wide
      neuropsychological battery. All subjects completed the comprehensive affect
      testing system (CATS), a group of computerized tests designed to evaluate emotion
      perception abilities. With respect to the controls, patients were not impaired in
      the CATS tasks involving discrimination of nonemotional prosody, naming of
      emotional stimuli expressed by voice and judging the emotional content of a
      sentence, whereas they showed a specific impairment in decoding emotion in a
      conflicting auditory condition and in the multichannel modality. Prosody
      impairment was affected by executive functions, attention and negative symptoms,
      while deficit in multisensory emotion recognition was affected by executive
      functions and negative symptoms. These emotion recognition deficits, rather than
      being associated purely with emotion perception disturbances in schizophrenia,
      are affected by core symptoms of the illness.

PMID- 22985541
TI  - Traveling waves in actin dynamics and cell motility.
AB  - Much of current understanding of cell motility arose from studying steady
      treadmilling of actin arrays. Recently, there have been a growing number of
      observations of a more complex, non-steady, actin behavior, including self
      organized waves. It is becoming clear that these waves result from activation and
      inhibition feedbacks in actin dynamics acting on different scales, but the exact
      molecular nature of these feedbacks and the respective roles of biomechanics and
      biochemistry are still unclear. Here, we review recent advances achieved in
      experimental and theoretical studies of actin waves and discuss mechanisms and
      physiological significance of wavy protrusions.

PMID- 22985543
TI  - The association between depressive symptoms and emotion recognition is moderated
      by emotion regulation.
AB  - In this study, we examined the associations between depression and aspects of
      emotional functioning, namely emotion recognition, affectivity and interpersonal
      problems. Particularly, the moderating role of emotion regulation in these
      interrelations was tested in a sample of 85 women, who exhibited a wide range of
      depressive symptoms (Composite International Diagnostic Interview (CIDI), Beck
      Depression Inventory (BDI)). Emotion recognition was assessed with a paradigm
      displaying a widely used set of photographs of the six basic emotions in graded
      intensities. Further, participants were examined regarding emotion regulation
      (Emotion Regulation Questionnaire (ERQ)), interpersonal problems (Inventory of
      Interpersonal Problems-Circumplex (IIP-C)) and affectivity (Affect Intensity
      Measure (AIM), Positive and Negative Affect Schedule (PANAS)). Besides
      correlation analyses, Johnson-Neyman technique for probing interactions in linear
      regression models was applied to test for possible moderating effects. Depressive
      symptoms were positively correlated with error rates in anger recognition, but
      not with the other basic emotions. This association was moderated by suppression
      in that regard that more severely depressed women who more frequently used
      suppression showed superior recognition of angry faces than those with lower
      suppression values. Further, suppression was associated with an affective
      imbalance and interpersonal problems in women with current depressive disorder.
      In sum, our results emphasize the importance of differentiating subtypes of
      depression depending on emotion regulation capabilities for research on or
      treatment of emotional functioning in depression.

PMID- 22985544
TI  - Lee Fatigue And Energy Scales: exploring aspects of validity in a sample of women
      with HIV using an application of a Rasch model.
AB  - This study examines the psychometric properties of the Lee Fatigue and Energy
      Scales (visual analog version) using a Rasch model application. The relationship
      between fatigue and energy is also described for a convenience sample of 102
      women with human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) who completed the Lee Fatigue and Energy Scales in the morning and
      evening. Both scales were assessed for internal scale validity,
      unidimensionality, and uniform differential item functioning in relation to
      morning and evening ratings. Analyses confirmed that both the Fatigue and Energy
      Scales demonstrated evidence of internal scale validity and unidimensionality.
      Mean fatigue measures were also higher in the evening than in the morning and
      mean energy measures were higher in the morning than in the evening (both
      p<0.001), indicating that time of day is an important consideration. Fatigue and
      energy measures were moderately correlated with each other in the morning but not
      in the evening. The concepts of energy and fatigue were inversely related, but
      not polar opposites in this sample. Fatigue and energy may therefore be distinct
      constructs that should not be used interchangeably, either in measurement or when
      interpreting outcomes for research or clinical purposes.

PMID- 22985545
TI  - Miscarriage and mental health: results of two population-based studies.
AB  - A miscarriage may have a sustained negative effect on mental health. Our aim was
      to analyze the association of the history and, if any, the number of miscarriages
      with mental health. The participants were women from two population-based
      studies, the Finnish Health 2000 survey and the National FINRISK 2002 Survey.
      Data were collected with a set of self-reported questionnaires, a clinical health
      examination and/or a home interview. A modified Beck Depression Inventory (BDI),
      the 12-item General Health Questionnaire (GHQ-12), the Munich-Composite
      International Diagnostic Interview (M-CIDI) and other non-structured interviews
      were used for the assessment of mental health. A diagnosis of depressive disorder
      and the presence of depressive symptoms were more prevalent among women with a
      history of miscarriage. In both datasets the higher the number of miscarriages
      was, the worse the current state of mood was and the higher the frequency of a
      psychiatric diagnosis was. These results suggest that a miscarriage, and in
      particular the number of miscarriages, contributes to mental health in a negative
      way for long.

PMID- 22985546
TI  - CACNA1C as a risk factor for schizotypal personality disorder and schizotypy in
      healthy individuals.

PMID- 22985548
TI  - Working memory as a predictor of negative symptoms and functional outcome in
      first episode psychosis.
AB  - The relationship of neurocognitive course with clinical and functional outcomes
      in psychosis is not well known, especially in the long term. The aim of the study
      was to examine the clinical and neuropsychological course of first-episode
      psychosis patients at 5-year follow-up and analyze the relationship of cognitive
      performance with clinical and functional outcome. The 5-year follow-up was
      conducted with 26 first-episode psychosis patients. Psychotic symptoms were
      measured by the Positive and Negative Syndrome Scale, manic and depressive
      symptoms by the Young Mania Rating Scale and Hamilton Depression Rating Scale
      respectively, and psychosocial functioning by the Functioning Assessment Short
      Test. The cognitive domains were assessed by the Wechsler Adult Intelligence
      Scale, the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency
      Test, the Stroop Colour-Word Test and the Wechsler Memory Scale. Patients showed
      symptomatic improvement in the follow-up except in negative psychotic symptoms.
      There was also improvement in most cognitive domains except in working memory and
      processing speed in the follow-up. Working memory impairment was associated to
      negative psychotic symptoms and poor functional outcomes. Negative symptoms
      mediated the relationship between working memory and outcome. Therefore, negative
      symptoms should be a primary target of treatment to improve functional outcomes.

PMID- 22985549
TI  - An association between both low and high birth weight and increased disorganized
      and negative symptom severity in schizophrenia and other psychoses.
AB  - Longitudinal cohort studies have implicated an association between both low and
      high birth weight and increased schizophrenia risk. In this study, we
      investigated the effect of birth weight on the symptom severity of psychotic
      disorders including schizophrenia in a Finnish schizophrenia family study sample.
      We used a multivariate GEE (General Estimating Equation) regression model to
      investigate the association of birth weight and symptom severity in 282 subjects
      with a primary psychotic disorder, 178 of whom had a diagnosis of schizophrenia.
      The Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS)
      were used as a measure of symptom severity. Sex, place of birth and year of birth
      were adjusted for in the model. Both low and high birth weight were associated
      with more severe symptoms with respect to bizarre behaviour, affective flattening
      and attentional impairment. In addition, low birth weight was associated with
      more severe symptoms with respect to positive formal thought. Our findings
      suggest that both low and high birth weight can influence the symptom severity of
      psychotic disorders. Our results implicate an association between both low and
      high birth weight and disorganized and negative symptoms.

PMID- 22985547
TI  - Selection of intervention components in an internet stop smoking participant
      preference trial: beyond randomized controlled trials.
AB  - To address health problems that have a major impact on global health requires
      research designs that go beyond randomized controlled trials. One such design,
      the participant preference trial, provides additional information in an
      ecologically valid manner, once intervention efficacy has been demonstrated. The
      current study presents illustrative data from a participant preference trial of
      an internet-based smoking cessation intervention. Participants (N=7763) from 124
      countries accessed the intervention and were allowed to choose from nine
      different site components to aid their quit attempt. Of consenting participants,
      36.7% completed at least one follow-up assessment. Individuals with depression
      were more likely to choose a mood management module and participants who smoked a
      higher number of cigarettes were more likely to choose a cigarette counter and a
      nicotine replacement therapy guide. Furthermore, depressed participants selecting
      the mood management component were more likely to report at least one successful
      7 day quit (37.2% vs. 22.2%) in the 12 months following the intervention. Thus,
      participants with depressive symptoms appear to make choices on the basis of
      their needs and to benefit from these decisions. This suggests that providing the
      ability to customize previously validated resources may be a successful way to
      widely disseminate interventions.

PMID- 22985550
TI  - Correlations between psychological tests and physiological responses during fear
      conditioning and renewal.
AB  - BACKGROUND: Anxiety disorders are characterized by specific emotions, thoughts
      and physiological responses. Little is known, however, about the relationship
      between psychological/personality indices of anxiety responses to fear stimuli.
      METHODS: We studied this relationship in healthy subjects by comparing scores on
      psychological and personality questionnaires with results of an experimental fear
      conditioning paradigm using a visual conditioned stimulus (CS). We measured skin
      conductance response (SCR) during habituation, conditioning, and extinction;
      subsequently testing for recall and renewal of fear 24 hours later. RESULTS: We
      found that multiple regression models explained 45% of the variance during
      conditioning to the CS+, and 24% of the variance during renewal of fear to the
      CS+. Factors that explained conditioning included lower levels of
      conscientiousness, increased baseline reactivity (SCL), and response to the shock
      (UCR). Low levels of extraversion correlated with greater renewal. No model could
      be found to explain extinction learning or extinction recall to the CS+.
      CONCLUSIONS: The lack of correlation of fear extinction with personality and
      neuropsychological indices suggests that extinction may be less determined by
      trait variables and cognitive state, and may depend more on the subject's current
      emotional state. The negative correlation between fear renewal and extraversion
      suggests that this personality characteristic may protect against post-treatment
      relapse of symptoms of anxiety disorders.

PMID- 22985551
TI  - Developmental analysis of liver metabolic proteins using mitochondrial antibody
      microarrays.
AB  - OBJECTIVE: To investigate the abundance of metabolic proteins in adult and fetal
      human livers. METHODS: Adult liver homogenate proteins, fetal liver homogenate
      proteins, adult liver mitochondrial proteins and fetal liver mitochondrial
      proteins were obtained from fetal or adult liver tissues and examined using the
      antibody microarrays containing 19 liver monoclonal mitochondrial antibodies. The
      protein expression abundances were compared among the 4 protein fractions and the
      pathways related to protein metabolisms were explored. RESULTS: In adult liver
      mitochondria, aldehyde oxidase and carbonyl reductase were up-regulated by 2.6
      and 1.7 folds, respectively, whereas corticosteroid 11-beta-dehydrogenase isozyme
      1, epoxide hydrolase 1 and fibrinogen beta chain protein were down-regulated by
      1.7, 1.9 and 2.2 folds, respectively, compared to those in fetal liver
      mitochondria. The abundance of epoxide hydrolase 1 and glutathione transferase
      omega-1 was significantly different between adult and fetal liver homogenate
      samples. CONCLUSION: Our results demonstrate a clear difference in the expression
      profiles of metabolic proteins in the liver between adults and human fetuses to
      allow a better understanding of the occurrence and development of the metabolic
      proteins and the identification of markers of liver metabolism.

PMID- 22985552
TI  - [Effect of maternal staphylococcal enterotoxin B administration during pregnancy
      on CD3+ TCR Vbeta8+T cells of adult offspring rats].
AB  - OBJECTIVE: To investigate the influence of maternal staphylococcal enterotoxin B
      (SEB) administration during pregnancy on CD3+ TCR Vbeta8+T cells of adult
      offspring rats. METHODS: Pregnant maternal rats at gestational day (GD) 16 were
      injected intravenously with 15 ug SEB in 0.2 ml PBS (SEB group), and the control
      rats receive the same volume of PBS. Flow cytometry was used to determine the
      levels of CD3+ TCR Vbeta8+T cells in both the thymus and peripheral blood of
      adult offspring rats and the response of these cells to a secondary SEB
      administration. RESULTS: Maternal SEB administration during pregnancy
      significantly decreased the percentages of CD3+TCR Vbeta8+T cells in the thymus
      in adult female (1.760-2.714) and male (1.098-2.088) offspring rats (P<0.05). The
      change of CD3+TCR Vbeta8+T cells in the peripheral blood was similar to that in
      the thymus. In the control adult offspring rats, SEB administration at adulthood
      significantly reduced the percentages of CD3+TCR Vbeta8+T cells in both the
      thymus and peripheral blood (P<0.05). But in SEB group, a secondary SEB
      administration in adult offspring rats significantly increased the percentage of
      CD3+TCR Vbeta8+T cells in the peripheral blood (P<0.05) but not in the thymus
      (P>0.05). CONCLUSION: Maternal SEB administration during pregnancy can change the
      response of CD3+ TCR Vbeta8+T cells of adult offspring rats to a secondary SEB
      administration.

PMID- 22985553
TI  - [Propensity score matching-based therapeutic effect evaluation in patients with
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the therapeutic effects of transcatheter arterial
      chemoembolization (TACE) with or without radiofrequency ablation (RFA) in
      hepatocellular carcinoma (HCC) patients based on propensity score matching.
      METHODS: A logistic regression model was established with the treatment
      assignment as the dependent variable and the covariates as the independent
      variables. For each HCC patient, the propensity score was calculated from the
      model for caliper matching, and a survival analysis of the matched data were
      carried out. RESULTS: The covariates between the groups were balanced after
      caliper matching based on the propensity scores. Before matching, the one-, two-,
      and three-year survival rates of TACE and TACE+RFA were 52.07% and 59.08%, 32.24%
      and 36.43%, and 316.54% and 19.39%, with the median survival time of 1.20 and
      1.40 years, respectively, showing no significant differences in the overall
      survival rate between the two groups. After matching, the 1-year, 2-year, and 3
      year survival rates of TACE and TACE+RFA groups were 54.39% and 62.28%, 23.15%
      and 40.08%, and 10.20% and 18.52%, with the median survival time of 1.10 years
      and 1.50 years, respectively, showing significant differences in the overall
      survival between the two groups. The survival rate in TACE+RFA group was higher
      than that of TACE only group. CONCLUSION: Propensity score matching can
      effectively reduce the confounding bias of non-randomized clinical observational
      data for a more accurate evaluation of the therapeutic effect in HCC patients.

PMID- 22985554
TI  - [Dehydroandrographolide succinate inhibits oxidative stress in mice with
      lipopolysaccharide-induced acute lung injury by inactivating iNOS].
AB  - OBJECTIVE: To investigate the effect of dehydroandrographolide succinate (DAS) on
      oxidative stress and induced nitric oxide synthase (iNOS) expression in a mouse
      model of lipopolysaccharide (LPS)-induced acute lung injury. METHODS: Thirty male
      BALB/C mice were randomly divided into control group, LPS+DAS group and LPS group
      (n=10). The levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor
      alpha (TNF-alpha), malondialdehyde (MDA) and superoxide dismutase (SOD) in the
      bronchoalveolar lavage fluid (BALF) were measured. The wet-to-dry ratio (W/D) of
      the lung tissue was determined to evaluate lung edema. HE staining was used to
      observe the pathological changes and lung injury scores. The expressions of iNOS
      mRNA and protein in the lungs were analyzed using RT-PCR and Western blotting,
      respectively. RESULTS: IL-1beta, IL-6, TNF-alpha and MDA levels in the BALF, W/D,
      lung injury scores, and iNOS mRNA and protein expressions increased and SOD in
      the BALF decreased significantly after intratracheal LPS injection. Compared with
      those in LPS group, IL-1beta, IL-6, TNF-alpha and MDA in BALF, W/D, lung injury
      scores and iNOS mRNA and protein expression were significantly reduced and SOD in
      the BALF significantly increased in LPS+DAS group. CONCLUSIONS:
      Dehydroandrographolide succinate can alleviate oxidative stress in LPS-induced
      acute lung injury possibly by inactivating iNOS.

PMID- 22985555
TI  - [Predictors of recurrence after pancreaticoduodenectomy for carcinoma of the
      ampulla of Vater].
AB  - OBJECTIVE: To investigate the predictors for recurrence of carcinoma ampulla of
      Vater following pancreatico- duodenectomy. METHODS: We reviewed the clinical data
      of 77 patients with carcinoma of the ampulla of Vater who received surgical
      intervention with pancreaticoduodenectomy. Independent t-test and chi(2) test
      were used for statistical comparison, and logistic regression was used for
      multivariate analysis to investigate the predictors for tumor recurrence
      following pancreaticoduodenectomy. RESULTS: The tumor recurred in 30 patients
      following the surgery. Univariate analysis showed that tumor size (P=0.008),
      tumor invasion depth (P=0.003), lymph node metastasis status (P=0.039), TNM
      staging (P=0.027), and grade of cell differentiation (P=0.019) were significant
      prognostic factors of carcinoma of the ampulla of Vater. Multivariate analysis
      identified tumor size (P=0.032) and grade of cell differentiation (P=0.027) as
      independent prognostic factors of the carcinoma. CONCLUSION: Distant failure is
      the predominant recurrence pattern of carcinoma of the ampulla of Vater after
      curative resections, and tumor size and grade of cell differentiation are the
      most important factors influencing the outcome of the patients.

PMID- 22985556
TI  - [K562 cells induces apoptosis of activated NK cells in vitro].
AB  - OBJECTIVE: To investigate the apoptosis of NK cells induced by the
      erythroleukemia cell line K562 in vitro. METHODS: Primary NK cells isolated from
      the peripheral blood of healthy donors by magnetic-activated cell sorting were
      cultured with stem cell medium containing recombinant human interleukin-2 (rhIL
      2). The NK cells and K562 cells were mixed and co-cultured at different E:T
      ratios for different time lengths. The apoptosis of NK cells and K562 cells were
      detected using PE-AnnexinV/7-AAD labeling and flow cytometry. RESULTS: The purity
      of isolated NK cells reached (93.99?4.22)%. At the same E: T ratio, the apoptotic
      rate of NK cells induced by K562 cells increased significantly with time. As the
      E:T ratio reduced, the apoptotic rate of the NK cells increased and their
      cytotoxic activity against K562 cells was attenuated. CONCLUSION: K562 cells can
      induce the apoptosis of activated NK cells, which is one of the probable
      mechanisms of immune escape of tumors.

PMID- 22985557
TI  - [Protein kinase C mediates thrombin-induced monocyte chemoattractant protein-1
      release from human lung fibroblasts].
AB  - OBJECTIVE: To investigate the role of protein kinase C (PKC) in thrombin-induced
      monocyte chemoattractant protein-1(MCP-1) release by human lung fibroblasts (HLF
      1). METHODS: Cultured human lung fibroblasts HLF-1 were incubated with different
      concentrations of PKC inhibitors before by thrombin stimulation. MCP-l protein
      levels in the supernatants were assessed using ELISA, and MCP-1 mRNA levels in
      the cell lysate were measured by quantitative real-time PCR. RESULTS: The broad
      spectrum PKC inhibitors bisindolylmaleimide I and RO-31-8220 obviously inhibited
      thrombin-induced MCP-l mRNA and protein expressions in HLF-1 cells, whereas
      Ca(2+)-dependent PKC inhibitor Go 6976 had no such effects. CONCLUSION: Ca(2+)
      independent PKC mediates thrombin-induced MCP-1 release in cultured HLF-1 cells.

PMID- 22985558
TI  - [Expressions of peroxiredoxin 1, peroxiredoxin 6 and GFAP in human brain
      astrocytoma and their clinical significance].
AB  - OBJECTIVE: To characterize the expressions of peroxiredoxin 1 (Prx1),
      peroxiredoxin 6 (Prx6) and glial fibrillary acidic protein (GFAP) in human brain
      astrocytoma and explore their clinical significance. METHODS: The protein and
      mRNA expression levels of Prx1, Prx6 and GFAP in human brain astrocytoma and
      normal brain tissue specimens were determined by Western blotting, RT-PCR and
      immunohistochemistry. RESULTS: The protein and mRNA expressions of Prx1 and Prx6
      increased significantly in the order of normal brain tissue, grade II
      astrocytoma, grade III astrocytoma and grade IV astrocytoma (P<0.05). The protein
      and mRNA expressions of GFAP decreased significantly in  grade III and IV
      astrocytoma compared with those in grade II astrocytoma and normal brain tissues
      (P<0.05). CONCLUSION: Prx1 and Prx6 may play important roles in the invasion and
      malignant development of human brain astrocytoma, and may serve as biomarkers for
      evaluating the invasiveness, malignancy and prognosis of the tumor as well as
      potential molecular targets in astrocytoma therapy.

PMID- 22985559
TI  - [Effect of injectable gelatin matrix as a hemostat for management of hepatic
      trauma in dogs under contrast-enhanced ultrasound guidance].
AB  - OBJECTIVE: To explore the efficacy of injectable gelatin matrix as a hemostatic
      agent for treatment of grade III-IV hepatic trauma to a canine model with
      contrast-enhanced ultrasound (CEUS) guidance. METHODS: Twenty-seven healthy adult
      dogs underwent celiotomy in induce grade III-IV hepatic trauma in the left
      lateral lobe of the liver. The dogs were then randomized into 3 groups, namely
      the treatment group in which the injectable hemostat was percutaneously injected
      into the injury site under CEUS guidance, and the positive and negative control
      groups with thrombin solution and normal saline treatment, respectively. Intra
      abdominal blood loss within 30 min postoperatively, and alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) 7 days postoperatively were compared
      among the groups. Follow-up CEUS was performed in each animal 7 days after the
      operation. RESULTS: The mean blood loss was 47.69 ml in the treatment group,
      significantly less than that in the positive control group (81.77 ml, P/0.01) and
      negative control group (110.35 ml, P<0.01). The treatment group had also
      significantly lower ALT and AST levels than the two control groups (ALT: 49.37,
      62.81, and 82.83 U/L, respectively, P<0.05; AST: 48.32, 67.16, and 82.54 U/L,
      respectively, P<0.05). In the treatment group, CEUS did not detect hepatic
      lesions or ascites as found in the two control groups, and the perfusion of the
      liver was homogeneous. CONCLUSION: The injectable hemostat injected under the
      guidance of CEUS can effectively control grade III-IV hepatic hemorrhage in the
      canine model and show strong effects of stopping bleeding and promoting wound
      healing.

PMID- 22985560
TI  - [Effects of different human adipose-derived cells in promoting human adipose
      tissue engraftment in nude mice].
AB  - OBJECTIVE: To explore the optimal seed cells derived from human adipose tissue
      for promoting the engraftment of transplanted adipose tissue in nude mice.
      METHODS: Human adipose tissue granules (0.3 ml) obtained from patients undergoing
      liposuction were mixed with hypoxic adipose-derived stem cells (ADCs, group A),
      ADCs (Group B), stromal vascular fraction (SVF) cells (group C), or pure adipose
      tissue granules in complete culture medium particles (group D). The mixtures were
      injected subcutaneously on the back of 6 nude mice, and the transplanted adipose
      tissues were harvested 3 months later to examine the engraftment using
      histological method and HE staining. RESULTS: The wet weights of the adipose
      grafts in groups B and C (91.67?1.472 mg and 96.67?5.164 mg, respectively) were
      similar (P>0.05), but both significantly higher than those in groups A and D
      (61.67?8.165 mg and 40.83 ?4.916 mg, respectively, P<0.05). The grafts in groups
      A, B and Cshowed a significantly higher blood vessel density than those in group
      D; the blood vessel density was the highest in group C (P<0.05) and similar in
      groups A and B (P>0.05). Histologically, the adipose grafts in groups B and C
      consisted predominantly of adipose tissue, with less necrosis and fibrosis than
      those in groups A and D (P<0.05). The fibrosis count was the highest in group D
      (P<0.05), and similar in groups B and C (P>0.05). CONCLUSION: The adipose-derived
      stem cells, especially ASCs and SVFs, can promote the engraftment of human
      adipose tissue in nude mice, indicating their potential clinical value in adipose
      tissue transplantation.

PMID- 22985561
TI  - [Screening of dengue II virus-binding molecules from Aedes albopictus C6/36
      cells].
AB  - OBJECTIVE: To screen the molecules binding dengue II virus expressed in Aedes
      albopictus C6/36 cells and characterize their biological functions. METHODS:
      Aedes albopictus C6/36 cells were infected with dengue II virus, and the virus
      were collected and purified. The total and membrane proteins of C6/36 cells were
      extracted and analyzed using 12% SDS-polyacrylamide gel (PAGE). After
      electrophoresis, the proteins were transferred to a nitrocellulose membrane, and
      virus overlay protein-binding assay (VOPBA) was carried out using an anti-dengue
      virus 1-4 monoclonal antibody. RESULTS: Two specific bands of 67 000 and 30 000
      occurred after VOPBA of the proteins from the cells incubated with the virus,
      while the negative control group did not show these specific bands. CONCLUSION:
      Two putative dengue virus receptor molecules of 67 000 and 30000 have been
      obtained from C6/36 cells using VOPBA, and their functional identification is in
      progress.

PMID- 22985562
TI  - [Endothelin-1 stimulates the expression of pacemaker channel I(f) in
      cardiomyocytes through a p38 MAPK-independent signaling pathway].
AB  - OBJECTIVE: To investigate the transcriptional regulation of pacemaker channel
      I(f) mediated by vasoactive peptide endothelin-1 (ET-1) in neonatal rat
      ventricular myocytes and its mechanism. METHODS: Neonatal rat ventricular
      myocytes were enzymatically isolated. I(f) current was recorded using the whole
      cell patch-clamp technique. The expression of hyperpolarization-activated cyclic
      nucleotide-gated channel (HCN) isoforms HCN2 and HCN4 were measured by
      quantitative RT-PCR. RESULTS: ET-1 increased the expression of HCN2 and HCN4 mRNA
      in a dose- and time-dependent manner. These effects were blocked by specific ETA
      receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. The
      effects of ET-1 on HCN2 and HCN4 mRNA expression were not affected by the p38
      mitogen-activated protein kinase (MAPK) inhibitor (SB-203580). CONCLUSION: These
      findings indicate that ET-1 stimulates the expression of pacemaker channel I(f)
      in cardiomyocytes via ETA receptor through a p38 MAPK-independent signaling
      pathway, which might be linked to the intrinsic arrhythmogenic potential of ET-1.

PMID- 22985563
TI  - [Expression profile of miRNAs in APP swe/PSDeltaE9 transgenic mice].
AB  - OBJECTIVE: To observe the changes of miRNA expression profiles in
      APPswe/PSdeltaE9 transgenic mice and explore the possible roles of miRNA in the
      pathogenesis of Alzheimer's disease. METHODS: Using miRNA chip technique, we
      examined the miRNA expression in the brain tissue of 6-month-old APPswe/PSdeltaE9
      transgenic mice, with age-matched wild-type mice as the control group. RESULTS:
      Twelve miRNAs showed differential expressions by more than two folds in
      APPswe/PSdeltaE9 transgenic mice, namely miRNA-135a, miRNA-135a-2*, miRNA-298,
      miRNA-466b-3p, miR-669-3p, miR-142-5p, miR-144, miR-466f-3p, miR-466g, miR-200a,
      miR-200b and miR-96. Five miRNAs were significantly down-regulated in the
      transgenic mice, including miRNA-135a, miRNA-135a-2*, miRNA-298, miRNA-466b-3p,
      and miR-669-3p. CONCLUSION: The 5 down- regulated miRNA may play important roles
      in the pathogenesis of AD in APPswe/PSdeltaE9 transgenic mice.

PMID- 22985564
TI  - [Effect of different therapeutic regimens on serum interleukin-21 levels in
      patients with chronic hepatitis B].
AB  - OBJECTIVE: To detect serum interleukin-21 (IL-21) levels in patients with chronic
      hepatitis B receiving different therapeutic regimens. METHODS: A total of 198
      patients with inactive chronic hepatitis B were divided into 3 groups according
      to the therapeutic regimens, namely interferon (IFN)-treated group (IFN group,
      n?38), nucleoside analogue-treated group (NA group, n?72) and untreated group
      (control group, n?88). IL-21 and serum hepatitis B virus (HBV) markers were
      detected in these patients using enzyme-linked immunosorbent assay (ELISA), and
      the liver function indices were measured with an auto-biochemical analyzer.
      RESULTS: The serum IL-21 levels in Con and IFN groups were significantly higher
      than those in NA group (102.29?14.03, 123.01?38.26, and 48.10?7.06 pg/ml,
      respectively, P<0.05). When all the patients were regrouped according to the
      status of HBeAg, serum IL-21 level was 114.83?19.88 pg/ml in HBeAg-negative group
      (n?105), significantly higher than that of 61.53?6.61 pg/ml in HBeAg-positive
      group (n?93) (P<0.05). Bivariate correlation analysis showed no significant
      correlations between IL-21 and liver function indices. CONCLUSION: The
      immunomodulator IFN might be capable of increasing serum IL-21 levels, while
      nucleoside analogues can decrease IL-21 level in patients with chronic hepatitis
      B. HBeAg-negative patients have a significantly higher serum IL-21 level,
      suggesting that the expression of HBeAg might result in IL-21 depression.

PMID- 22985565
TI  - [Therapeutic effect of zoledronic acid on primary osteoporosis in elderly
      patients].
AB  - OBJECTIVE: To observe the effect of zoledronic acid on bone mineral density (BMD)
      and bone metabolic markers in elderly patients with primary osteoporosis.
      METHODS: Forty-eight elderly patients with osteoporosis were randomly assigned to
      zoledronic acid group (n=23) to receive treatment with 5 mg zoledronic acid once
      a year and the control group (n=25). In both groups, the patients were given
      Vitamin D3 and caltrate on a daily basis for a year. The bone mineral density
      (BMD) and bone metabolic markers were observed after the treatment. RESULTS:
      Compared with the control group, zoledronic acid group had significantly higher
      L1-4, neck, Inter and Ward's BMD (P<0.05) with reduced B-NTX (P<0.05). The N-MID
      and CT showed no significant differences between the two groups (P<0.05).
      CONCLUSION: Zoledronic acid administration once a year can increase BMD and lower
      the serum bone turnover metabolism, and can be used in the treatment of primary
      osteoporosis in elderly patients.

PMID- 22985566
TI  - [CA916798 gene participates in cisplatin resistance of human lung adenocarcinoma
      A549 cells through PI3K/AKT/mTOR pathway].
AB  - OBJECTIVE: To observe the changes of CA916798 gene expression in human lung
      adenocarcinoma cell A549 and the multidrug-resistant cell line A549/CDDP after
      blocking the PI3K/AKT/mTOR pathway. METHODS: Human lung adenocarcinoma cell lines
      A549 and A549/CDDP were treated with rapamycin and LY294002, and the cell growth
      changes in response to subsequent cisplatin treatment was observed; RT-PCR was
      performed to detect CA916798 mRNA expression in the treated cells. RESULTS:
      Blocking PI3K/AKT/mTOR pathway with rapamycin and LY294002 significantly reduced
      drug resistance of both A549 and A549/CDDP cells to cisplatin and obviously
      decreased the expression of CA916798 gene mRNA (P<0.05). CONCLUSION: CA9167981
      gene is located downstream of the PI3K/AKT/mTOR pathway, which might be one of
      the mechanisms of CA916798 to cause cisplatin resistance in the tumor cells.

PMID- 22985567
TI  - [Linearly polarized near-infrared irradiation combined with aerothermotherapy for
      treatment of frozen shoulder in diabetic patients].
AB  - OBJECTIVE: To evaluate the effect of linearly polarized near-infrared irradiation
      (Super Lizer) combined with aerothermotherapy in the treatment of patients with
      frozen shoulder and diabetes. METHODS: Eighty-four diabetic patients with frozen
      shoulder were randomized into 3 groups to receive a 20-day treatment with drug
      therapy and shoulder exercise (control group), daily linearly polarized near
      infrared irradiation in addition to the control therapy (Super Lizer group), or
      daily Super lizer and aerothermotherapy (S+P group) in addition to the control
      therapy. Visual analogue scale was used to assess the changes in the pain
      intensity, and the shoulder movement was assessed using shoulder movement
      disorder degree integral scores. RESULTS: After the 20-day treatment, the VAS
      scores and shoulder movement disorder degree integral scores in the 3 groups all
      significantly decreased (P<0.05), and these scores in Super Lizer group and S+P
      group were significantly lower than those in the control group (P<0.05). The cure
      rate in S+P group was significantly higher than that in the other two groups
      (P<0.01). CONCLUSION: Linearly polarized near-infrared irradiation combined with
      aerothermotherapy is effective for treatment of patients with frozen shoulder and
      diabetes with a high cure rate and short treatment course.

PMID- 22985568
TI  - [Surgical resection of complex sphenoclival lesions via a whole-course endoscopic
      extended transsphenoidal approach under neuronavigation: report of 15 cases].
AB  - OBJECTIVE: To study the clinical value of the whole-course endoscopic extended
      transsphenoidal approach assisted by neuronavigation in surgical resection of
      complex sphenoclival lesions. METHODS: Image reconstruction and registration were
      performed for 15 patients with complex sphenoclival lesions using the
      neuronavigation system, and the bilateral nasal extended transsphenoidal approach
      was adopted to remove the lesions with a whole-course endoscopic procedure.
      RESULTS: Postoperative pathological examination reported pituitary adenomas in 7
      cases, chordomas in 5 cases, and cavernous angiomas in 3 cases. Total removal of
      the lesions was achieved in 10 cases, subtotal removal in 4 cases, and partial
      removal in 1 case. Transient polyuria occurred in 3 cases and 2 patients
      experienced temporary cerebrospinal rhinorrhea. No death occurred in these cases
      after the operation. During the follow-up ranging from 3 to 26 months, only 2
      patients with partial lesion removal showed recurrence and received subsequent
      radiotherapy. CONCLUSION: The combination of whole-course endoscopic technique
      and neuronavigation can help improve the surgical outcomes and reduce
      complications of complex sphenoclival lesion removal via the extended
      transsphenoidal approach.

PMID- 22985569
TI  - [Effect of ulinastatin pretreatment on liver regeneration and TNF-alpha/IL-6/STAT
      3 signal pathway in rats with major hepatectomy and ischemia-reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of pretreatment with ulinastatin on liver
      regeneration and TNF-alpha/IL-6/STAT-3 signal pathway in rats after 70%
      hepatectomy combined with ischemia-reperfusion injury. METHODS: A total of 120
      normal male SD rats weighing 230-280 g were randomized into 3 groups (n=40),
      namely simple partial hepatectomy (PH) group, partial hepatectomy with ischemia
      reperfusion (PHIR) group, and ulinastatin group. All the rats received resection
      of the left and middle liver lobes. In PHIR group, the remnant right lobes were
      subjected to blood flow occlusion for 30 min; in UTI group, the rats were given
      50 000 U/kg UTI intravenously prior to the occlusion, and in PH group, the blood
      flow was not occluded. At 1, 6, 12, 24, and 48 after the reperfusion, the remnant
      liver tissues were examined for regenerated liver weight, PCNA staining, TNF
      alpha and IL-6, STAT-3, cyclin D1, and Cdk4 expressions. RESULTS: The regenerated
      liver weight and PCNA positivity rates were significantly higher in ulinastatin
      group than in PHIR group at 24 h and 48 h after the reperfusion (P<0.05). In
      ulinastatin group, the levels of TNF-alpha and IL-6 were significantly lower, and
      IL-6 level and the expressions of STAT-3, cyclin D1, and Cdk4 mRNA and cyclin D1
      and Cdk4 proteins were significantly higher in ulinastatin group than in PHIR
      group at 24 h and 48 h (P<0.05). CONCLUSION: Ulinastatin can promote liver
      regeneration after major hepatectomy and ischemia-reperfusion injury, and the
      effect is possibly related with activation of IL-6/STAT-3 signal pathway, which
      promotes the synthesis of cyclin Dl-Cdk4 complex and hepatocyte proliferation.

PMID- 22985570
TI  - [Mechanism of phenotype difference in biofilm formation by Candida albicans
      isolated from the respiratory tract].
AB  - OBJECTIVE: To explore the molecular mechanism of the differences in biofilm
      formation abilities of Candida albicans isolated from the respiratory tract.
      METHODS: The biofilms formed by Candida albicans isolates from the respiratory
      tract and the standard strain ATCC90028 were examined for bacterial proliferation
      using XTT reduction assay. The mRNA expression of CPH1, EFG1, ALS3 and HWP1 in
      the isolates were measured with fluorescent quantitative RT-PCR. RESULTS: XTT
      reduction assay demonstrated a strong ability of biofilm formation in 8 clinical
      isolates, and a relatively low biofilm formation ability in 7 clinical isolates
      and ATCC90028 strain. The strong and weak biofilm formers showed significant
      differences in ALS3 and HWP1 mRNA expressions (P<0.05) but not in EFG1 or CPH1
      mRNA expressions (P>0.05). CONCLUSION: The clinical isolates from the respiratory
      tract have different biofilm formation abilities under regulation by genes other
      than the transcription factors CPH1 and EFG1.

PMID- 22985571
TI  - [Effects of abdominal compartment syndrome on circulation and respiratory
      function in rabbits].
AB  - OBJECTIVE: To establish a rabbit model of abdominal compartment syndrome (ACS)
      and evaluate the impact of ACS on cardiovascular and respiratory functions and
      blood electrolyte levels in rabbits. METHODS: Twenty-four New Zealand rabbits
      were randomly allocated into 4 equal groups, namely the normal control group,
      ACS(5>?) group [intra-abdominal pressure (IAP)=5 mmHg], ACS(10) group (IAP=10
      mmHg) and ACS(20) group (IAP=20 mmHg). ACS model was established by intra-
      abdominal bleeding (IAB) with intra-abdominal hypertension (IAH). All the data
      were recorded 1 h after inducing IAH including cardiovascular parameters (LVSP,
      LVEDP, ?dp/dt max, SP, DP, HR, CVP), respiratory function (RR, PaO(2), PaCO(2),
      [HCO(3)(-)]), blood pH, and electrolyte level ([K(+)]). RESULTS: Compared with
      those in the normal control group, ACS20 group showed significantly decreased
      LVSP, LVEDP, ?dp/dt max, SP, DP, HR, RR, PaO(2), [HCO(3)(-)], and blood pH but
      increased CVP, PaCO(2), and K(+) (P<0.05). In ACS(10) group, all the parameters
      except for RR and PaO(2) showed similar changes as seen in ACS(20) group (P<0.05)
      but with lower amplitudes of variations. In ACS(5) group, only LVSP and HR were
      reduced remarkably (P<0.05) while the other parameters showed no significant
      variations. CONCLUSION: IAB plus IAH may cause damage to the cardiovascular and
      respiratory functions and lead to ACS in rabbits.

PMID- 22985572
TI  - [Effect of small-dose remifentanil on cardiovascular response to tracheal
      extubation after general anesthesia].
AB  - OBJECTIVE: To explore the efficacy and safety of small-dose remifentanil for
      attenuating cardiovascular response to tracheal extubation after surgery with
      general anesthesia. METHODS: A total of 164 patients scheduled for upper
      abdominal operation were randomized into groups A (n=41), B (n=43), C (n=40) and
      D (n=40). In groups A, B, and C, the patients received continuous infusion of
      remifentanil at the doses of 0.05, 0.10 and 0.20 ug.kg(-1).min(-1), respectively,
      while those in group D were not given any drug before tracheal extubation. The
      change of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart
      rate (HR) were recorded before induction of anesthesia (T1), at the time of
      extubation (T2), and at 1 min (T3), 3 min (T4), and 5 min (T5) after extubation.
      The recovery time and adverse effect of extubation were recorded. RESULTS: In
      each group, SBP, DBP and HR at T2 and T3 were significantly higher than those at
      T1 (P<0.05). SBP, DBP and HR were significantly higher in groups A, B and C than
      in group D (P<0.05), and significantly higher in groups A and B than in group C.
      The time of spontaneous breath recovery and awaking showed no significant
      difference in the 4 groups (P>0.05). The rates of adverse effect (nausea and
      vomiting) in groups A and B were significantly lower than that in group C
      (P<0.05), but comparable between groups A and B (P>0.05). CONCLUSIONS:
      Remifentanil at the optimal dose of 0.10 ug.kg(-1).min(-1) can effectively
      prevent cardiovascular response to tracheal extubation and reduce the adverse
      effect associated with anesthesia without prolonging the recovery time.

PMID- 22985573
TI  - [Evaluation of the biological properties of a highly efficient tissue cell
      preservative].
AB  - OBJECTIVE: To evaluate the performance of a new highly efficient and environment
      friendly tissue cell fixatives for preserving the morphologies and properties of
      pleural and peritoneal effusions. METHODS: Fifty-six specimens of tissue cells
      from pleural and peritoneal effusions were preserved using the new preservative
      or 95% ethanol. HE staining and Western blotting were employed to detect the
      morphologies and protein expression levels of CK, CEA and P53 of the cells after
      fixation. RESULTS: The new preservative well preserved the morphologies of the
      cells from the pleural and peritoneal effusions, and the nuclei and cytoplasm
      were intact with little debris. The conventional preservative (95% ethanol)
      caused noticeable structural damage of the tissue cells, especially the cytoplasm
      where obvious debris were seen after fixation. CK, CEA and P53 protein expression
      levels in the cells were 91%, 86% and 88% after fixation with the new
      preservative, significantly higher than those (46%, 38% and 31%, respectively) in
      cells fixed with 95% ethanol (P<0.05). CONCLUSION: The new preservative is
      efficient and environment-friendly for preserving the morphologies as well as the
      proteins of tissue cells from pleural and peritoneal effusions well,
      demonstrating its potential in tissue cell fixation and preservation.

PMID- 22985574
TI  - [Association of natural killer T cells with staging of endometriosis].
AB  - OBJECTIVE: To investigate the role of natural killer T cells (NKT) in the
      pathogenesis and staging of endometriosis (EMT). METHODS: Sixty EMT cases of
      stages I to IV were enrolled as the observation group, and 20 healthy volunteers
      served as the control group. NKT percentages in the peripheral blood and
      peritoneal effusions were detected by flow cytometry, and the levels of
      interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were examined using ELISA.
      RESULTS: Compared with the control group, EMT group showed significantly lowered
      NKT percentages and IFN-gamma and IL-4 levels in both the peripheral blood and
      peritoneal effusions (P<0.05). In EMT patients, NKT percentages, IFN-gamma and IL
      4 levels all increased significantly with the stage of EMT in the order of
      I>II>III>IV (P<0.05). Spearman correlation analysis showed that NKT, IFN-gamma
      and IL-4 were all inversely correlated with the stage of EMT (r>0.06, P<0.05).
      CONCLUSION: As a protective factor against EMT, NKT, together with its cytokines
      IFN-gamma and IL-4, play an important role in EMT and is closely correlated with
      EMT staging.

PMID- 22985575
TI  - [Association of fat distribution with metabolic syndrome in patients with
      polycystic ovary syndrome].
AB  - OBJECTIVE: To study the characteristics of the metabolic syndrome (MS) in
      patients with polycystic ovary syndrome (PCOS). METHODS: Oral glucose tolerance
      test (OGTT) was performed in 336 patients with PCOS, and the serum levels
      triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol and testosterone were measured. RESULTS: The
      total incidence of MS was 18.8% in these 336 patients with PCOS. The incidence of
      MS increased with percent body fat (%BF) and lipid accumulation product (LAP) in
      patients with PCOS. The patients at child-bearing age appeared to have a higher
      incidence of MS than those in puberty. The muscle distribution coefficient, age,
      body mass index, and the metabolic parameters were all higher in patients with MS
      than in those without MS. The bilateral lower limb muscle strength were lower in
      patients with MS than in those without, but the level of testosterone showed no
      significant difference between them. CONCLUSION: The risk of MS increases with
      BF%, age and LAP in patients with PCOS.

PMID- 22985576
TI  - [Microtubule-associated protein 2 and nestin expressions in human embryonic and
      fetal gastric tissues].
AB  - OBJECTIVE: To investigate the role of microtubule-associated protein 2 (MAP-2)
      and nestin in gastric development in human embryos and fetuses. METHODS:
      Immunohistochemistry was used to detect the expressions of MAP-2 and nestin
      proteins in the gastric cardia, pyloric and gastric tissues of human embryos and
      fetuses during the second, third and fourth month of development. RESULTS: In the
      second to fourth months of gestation, MAP-2 and nestin expressions were detected
      in the neural cells and neural fibers of the intermuscular nerve plexus and
      submucosal plexus in the gastric cardia, pyloric and gastric tissues. As the
      gestational age increased, the number of MAP-2- and nestin-positive cells and the
      expression intensity all increased in the myenteric plexus, but MAP-2 and nestin
      expressions were negative in the glandular and mucosal tissues of human embryonic
      and fetal gastric cardia, pylorus or gastric walls. CONCLUSION: MAP-2 and nestin
      participate in the regulation of the development of gastric tissues in human
      embryos.

PMID- 22985577
TI  - [Magnetic-activated cell sorting combined with multiplex ligation-dependent probe
      amplification for detecting molecular cytogenetic abnormalities in multiple
      myeloma].
AB  - OBJECTIVE: To investigate the reliability of magnetic-activated cell sorting
      (MACS) combined with multiplex ligation-dependent probe amplification (MLPA) in
      the detection of the molecular cytogenetic abnormalities in multiple myeloma.
      METHODS: The bone marrow cells were collected from 29 patients with multiple
      myeloma. The immuno magnetically sorted and unsorted cells were detected for TP53
      and RB1 expressions using MLPA probes and the results were compared with
      fluorescent in situ hybridization (FISH). RESULTS: The detection success rate was
      100% for MLPA, which yielded results with an concordance rate of 99.1% with the
      FISH results. The positivity rates of MLPA and FISH were both increased after
      immunomagnetic sorting of the bone marrow cells. CONCLUSION: MLPA can well suit
      the clinical needs for detecting molecular cytogenetic abnormalities in multiple
      myeloma, and the samples should be immuno magnetically sorted before the assay.

PMID- 22985578
TI  - [Correlation of the expressions of MMPs-9, TIMP-1 and TIMP-2 with cesarean
      section scar].
AB  - OBJECTIVE: To investigate the roles of MMPs-9, TIMP-1 and TIMP-2 in cesarean
      section scar healing. METHODS: The expressions of the MMPs-9, TIMP-1 and TIMP-2
      were detected by EnVision immunohistochemistry in 22 pregnant women with serious
      complications of the uterine scar, including 8 with early caesarean scar
      pregnancy (CSP) and 14 with full-term pregnancy undergoing hysterectomy for
      placenta previa or implanted placenta. Thirty-eight full-term pregnant women
      without serious complications of the uterine scar and 32 normal full-term
      pregnant women served as the control I and control II groups, respectively.
      RESULTS: The expressions of MMPs-9 and TIMP-1 differed significantly between the
      3 groups (P<0.05), whereas TIMP-2 did not (P>0.05). Spearman rank correlation
      analysis showed that the expression of MMPs-9 in the uterine scar tissues was
      positively correlated with poor uterine scar healing with the correlation
      coefficients of 0.309 and 0.643. An increased severity of poor healing scar was
      associated with a significantly increased expression of MMPs-9 (P<0.05).
      CONCLUSION: The imbalanced expressions of MMPs-9 and TIMP-1 in injury repair can
      be related to poor uterine scar healing and CSP.

PMID- 22985579
TI  - [Hydroxycamptothecin inhibits proliferation of human lung carcinoma cell line
      A549 and down-regulates its Bcl-2 gene expression in vitro].
AB  - OBJECTIVE: To investigate the effect of hydroxycamptothecin (HCPT) on the
      proliferation, cell cycle and apoptosis of human lung carcinoma cell line A549.
      METHODS: The growth of A549 cells exposed to HCPT was observed by staining with
      acridine orange/ethidium bromide dye. Agarose gel electrophoresis was performed
      to detect DNA fragmentation of the apoptotic cells. The cell cycle distribution
      of the exposed cells was analyzed using flow cytometry, and cell apoptosis was
      examined with annexin V-FITC/PI staining. RT-PCR was used to investigate Bcl-2
      gene expression changes in the exposed cells. RESULTS: Agarose gel
      electrophoresis of the DNA from HCPT-treated cells showed a DNA ladder, and
      typical apoptotic appearance of the exposed cells was observed under fluorescence
      microscope. Treatment of A549 cells with 1 umol/L HCPT for 24 h resulted in a
      cell apoptosis rate of 18.11%, significantly higher than the rate in control
      cells (0.09%, P<0.05). The treatment also caused a significant reduction of Bcl-2
      mRNA expression by 70% (P<0.05). CONCLUSION: HCPT can significantly inhibit the
      proliferation, induce apoptosis, and down-regulate Bcl-2 gene expression in human
      lung carcinoma cell line A549, suggesting the involvement of Bcl-2 gene in the
      inhibitory effect of HCPT on A549 cells.

PMID- 22985580
TI  - [Clinical value of serum total P1NP, beta-CTX and 25(OH)D3 detection in
      evaluating risks of fragile hip fracture in elderly patients with osteoporosis].
AB  - OBJECTIVE: To investigate the clinical value of serum total procollagen type 1
      aminoterminal propeptide (total P1NP), cross-linked C-terminal telopeptide of
      type I collagen (beta-CTX) and 25(OH)D3 detection in evaluating the risks of
      fragile hip fracture in elderly patients with osteoporosis. METHODS: Serum levels
      of total P1NP, beta-CTX and 25(OH)D3 was measured in 68 elderly osteoporotic
      patients with fragile hip fracture and 68 age- and gender-matched osteoporotic
      controls without fragile hip fracture. In both groups, bone mineral density (BMD)
      was detected with dual X-ray absorptiometry. RESULTS: The serum levels of total
      P1NP and beta-CTX were significantly higher and 25(OH)D3 level was significantly
      lower in fragile hip fracture group than in the control group (P<0.05), but the
      two groups showed no significant difference in lumbar or total hip BMD. Bivariate
      correlation analysis suggested that in fragile hip fracture group, serum 25(OH)D3
      level was positively, while serum total P1NP and beta-CTX levels were inversely
      correlated with lumbar and total hip BMD (P<0.05). In control group, 25(OH)D3 was
      not related to lumbar or total hip BMD, and serum total P1NP and beta-CTX levels
      were inversely correlated with total hip BMD (P<0.05) but not related to lumbar
      BMD. CONCLUSION: In osteoporotic elderly patients with close BMD levels, high
      serum levels of total P1NP and beta-CTX and low serum levels of 25(OH)D3 might
      independently indicate high fragile hip fracture risk, and detection of the three
      markers can help identify high-risk individuals.

PMID- 22985582
TI  - [Clinical value of seminal paraoxonase-1 activity evaluation in the diagnosis of
      male infertility].
AB  - OBJECTIVE: To investigate the changes in seminal paraoxonase-1 (PON-1) activity
      in infertile male patients and assess the clinical value of seminal PON-1
      examination in the diagnosis of male infertility. METHODS: Seminal PON-1 activity
      was detected by spectrophotometric method in the semen samples from 270 infertile
      male patients and 50 health fertile males (control), and the semen parameters
      were analyzed using a computer-assisted semen analysis system. RESULTS: In the
      male infertility group, seminal PON-1 activity was 1.22?0.76 U/L in the patients
      with normal semen parameters and 0.64?0.54 in the patients with abnormal semen
      parameters, both significantly lower than that of the control group (3.17?0.89
      U/L, P<0.01). In patients with asthenospermia, the declined sperm motility was
      associated with decreased seminal PON-1 activity, which showed significant
      differences between patients with mild, moderate, and severe asthenospermia.
      Seminal PON-1 activity was positively correlated with the percentage of sperm
      viability (P<0.01), but inversely with the percentage of morphologically abnormal
      sperm (P<0.01). According to ROC curves, the area of seminal PON-1 activity under
      the curve was 0.907, showing a statistical significance (P<0.01). CONCLUSION: The
      detection of seminal PON-1 activity can provide a laboratory evidence for the
      diagnosis of male infertility.

PMID- 22985581
TI  - [Effects of levonorgestrel-releasing intrauterine system on endometrial estrogen
      and progesterone receptors in patients with endometrial hyperplasia].
AB  - OBJECTIVE: To investigate the changes in local endometrial contents of estrogen
      receptors (ER) and progesterone receptors (PR) after insertion of levonorgestrel
      releasing intrauterine system (LNG-IUS) and evaluate the efficacy of LNG-IUS in
      treating endometrial hyperplasia. METHODS: The endometrial histological changes
      were observed in 25 anovulatory women with dysfunctional uterine bleeding after
      insertion of LNG-IUS, and the contents of ERs and PRs in the endometrium were
      measured by immunohistochemistry. RESULTS: The endometrial proliferation activity
      was obviously inhibited 6 months after LNG-IUS insertion with decreased
      endometrial glands, glandular dysplasia and decidualization of interstitial
      cells. The positive cell rate for ERs and PRs in the glandular epithelial and
      interstitial cells were significantly reduced after LNG-IUS insertion.
      CONCLUSIONS: LNG-IUS can reduce ER and PR expressions in the endometrium and
      inhibit endometrial proliferation, and therefore can be effective in treating
      simple and complex endometrial hyperplasia.

PMID- 22985583
TI  - [Posterior fixation and fusion for treatment of Os odontoideum complicated by
      atlantoaxial dislocation].
AB  - OBJECTIVE: To summarize the techniques and evaluate the therapeutic effect of
      posterior fixation and fusion in the treatment of Os odontoideum complicated by
      atlantoaxial dislocation. METHODS: From March, 2007 to October, 2010, 10 patients
      with Os odontoideum (including 6 male and 4 female patients aged from 20 to 65
      years, mean 39.8 years) were treated in our hospital. Before and after the
      operation, the patients underwent X ray, CT and MRI examinations to measure and
      evaluate the degree of dislocation and neural compression. After preoperative
      traction for 1-2 weeks, all the 10 patients showed deductible atlantoaxial
      dislocation. Through a posterior approach, Atlantoaxial pedicle screws fixation
      were performed in 9 cases, and C2/3 pedicle-Occiput screw fixation was performed
      in 1 case. All the patients wore cervical collars as external support for 3
      months after the operation. RESULTS: The mean operative time was 3 h in these
      patients with a mean intraoperative blood loss of 420 ml. The symptoms were
      relieved after the surgery in all the patients, who showed no neck pain or
      neurological defects. The patients were followed up for 6 to 52 months (mean 22
      months), and bony fusion was observed in all the 10 cases within 6 to 8 months
      without such complications as internal fixation failure or redislocation of the
      atlas. CONCLUSION: Patients with Os odontoideum complicated by atlantoaxial
      dislocation should undergo surgical stabilization to avoid severe neurological
      injury. Pedicle screw instrument in the atlas allows restoration of the spinal
      stability, short-segment fusion, and maximal preservation of the mobility of the
      neck.

PMID- 22985584
TI  - [Impact of obstructive sleep apnea-hypopnea syndrome on cerebral microbleeds in
      patients with cerebral infarction].
AB  - OBJECTIVE: To investigate the impact of obstructive sleep apnea-hypopnea syndrome
      (OSAHS) on cerebral microbleeds (CMBs) in patients with cerebral infarction.
      METHODS: Consecutive patients with acute cerebral infarction who had cerebral
      microbleeds shown by susceptibility-weighted imaging (SWI) were enrolled to
      undergo polysomnography (PSG). The patients were divided into two groups, namely
      non-OSAHS group with apnea-hypopnea index (AHI) less than 5 and OSAHS group with
      greater AHI, and the clinical and radiological features of cerebral microbleeds
      were compared between them. RESULTS: Forty-nine patients were enrolled in this
      study, including 27 (55.1%) with both cerebral infarction and OSAHS and 22
      (44.9%) with cerebral infarction but not OSAHS. A comparison of the risk factors
      showed that hypertension, a smoking history, and a history of stroke were more
      prevalent in patients with OSAHS than in those without OSAHS (P<0.05). The
      incidences of subclinical stroke in OSAHS and non-OSAHS patients were 37.0%
      (10/27) and 9.0% (2/22) (P<0.05), respectively. Neurological imaging revealed a
      greater number of cerebral microbleeds in OSAHS group than in non-OSAHS group
      (P<0.05). In OSAHS patients, 77.8% of the microbleeds were distributed in
      cortical-subcortical areas, 55.6% in the basal ganglia area, and 25.9% in the
      infratentorial area, as compared to the percentages of 50.0%, 40.9% and 50.0% in
      non-OSAHS patients, respectively (P<0.05). In OSAHS patients, 40.7% also had
      leukoaraiosis, and 48.1% had two or more causes, as compared to the percentages
      of 13.6% and 18.2% in non-OSAHS patients, respectively (P<0.05). CONCLUSIONS:
      OSAHS can be a risk factor for cerebral microbleeds. Patients with both cerebral
      infarction and OSAHS tend to have greater and more extensive lesions of cerebral
      microbleeds, more complicated cause of the disease, and a grater likeliness of
      stroke recurrence.

PMID- 22985585
TI  - [Changes of peripheral blood CD4(+)CD25(+) regulatory T cells and TREG-related
      Foxp3 gene expression at the onset of chronic allograft nephropathy].
AB  - OBJECTIVE: To investigate the changes of CD4(+)CD25(+) regulatory T cells (TREG)
      and TREG-related foxp3 gene expression in the peripheral blood at the onset of
      chronic allograft nephropathy (CAN) after kidney transplantation. METHODS: Twenty
      five patients with initial onset of CAN were examined for
      CD4(+)CD25(+)high/CD4(+) ratio and the expression of Foxp3 gene in the peripheral
      blood using the flow cytometry, and the data were compared with those of 30
      kidney recipients with normal graft function, 20 patients with chronic renal
      function (CRF), and 20 normal subjects. All the recipients had no more than 1 HLA
      mismatch and received the same inductive and maintenance drug treatment. RESULTS:
      The recipients with CAN had significantly lower CD4(+)CD25(+)high/CD4(+) ratio
      and Foxp3 gene expression compared with those with normal graft function
      (0.71?0.33 vs 1.17?0.25 and 62.75?10.80 vs 70.42?6.8, respectively, P<0.01). The
      recipients with normal renal graft function showed no significant difference in
      CD4(+)CD25(+)high/CD4(+) ratio and Foxp3 gene expression from the normal control
      subjects. CONCLUSION: The peripheral blood CD4(+)CD25(+)high/CD4(+) ratio and
      Foxp3 expression in the kidney recipients with CAN are significantly lower than
      those of recipients with normal renal graft function, which does not correlate
      with elevated creatinine level, suggesting a role of TREG in the occurrence and
      development of CAN.

PMID- 22985586
TI  - [Impact of maternal hepatitis B surface antigen carrier status on preterm
      delivery in southern China].
AB  - OBJECTIVE: To explore the impact of maternal hepatitis B surface antigen (HBsAg)
      carrier status on the occurrence of preterm birth. METHODS: We analyzed pregnancy
      related complications, outcomes and fetal growth index in 188 HBsAg positive
      singleton pregnant women during the period of May 2009 to July 2011, with 265
      HBsAg-negative women with singleton pregnancies in the same period serving as
      controls. RESULTS: The HBsAg-positive pregnant women showed a significantly
      higher incidence of placenta praevia than the control group (2.66% vs 0%,
      P=0.03), and the incidence of preterm delivery (<37 weeks) was also significantly
      higher in HBsAg-positive group (12.23% vs 6.04%, P=0.02). The incidences of
      gestational hypertension, preeclampsia, gestational diabetes mellitus, abnormal
      glucose tolerance, premature rupture of membranes, cesarean delivery, and
      postpartum hemorrhage showed no significant differences between the two groups
      (P>0.05), nor did the fetal birth weight, height, head circumference or Apgar
      scores at 1, 5, and 10 min (P>0.05). Logistic regression identified HBsAg
      positivity, abnormal ALT, placenta praevia, and severe preeclampsia as the risk
      factors for preterm delivery. CONCLUSION: HBsAg carrier status can increase the
      risk of preterm delivery in pregnancy, but it does not seem to affect the fetal
      growth.

PMID- 22985587
TI  - [Serum APPL1 level is elevated in newly diagnosed cases of type 2 diabetes
      mellitus].
AB  - OBJECTIVE: To investigate serum APPL1 level in patients with newly diagnosed type
      2 diabetes mellitus (T2DM) and analyze its correlation with body mass index
      (BMI), waist-to-hip ratio (WHR), blood pressure, fasting plasma glucose, fasting
      blood insulin, HbA1c, and insulin resistance (HOMA-IR). METHOD: Serum APPL1
      levels were determined using ELISA in 22 normal control subjects and 63 patients
      with newly diagnosed T2DM, and HOMA-IR of the subjects was calculated using the
      HOMA model. RESULTS: The diabetic patients had significantly elevated levels of
      serum APPL1 compared with the control subjects (85.71?27.39 vs 64.52?16.28 pg/ml,
      P<0.01), with also significantly increased BMI, WHR, SBP, FINS, LgHOMA-IR
      (P<0.01) and LDL-C (P<0.05) but lowered HDL-C (P<0.01). Fasting serum APPL1
      levels were positively correlated with FPG, FINS, and HOMA-IR (r=0.215, 0.297,
      0.334, P=0.014, 0.006, 0.002, respectively). In multiple linear regression
      analysis with APPL1 as the dependent variable, HOMA-IR (beta=0.329, P=0.002) was
      included in the equation. CONCLUSION: Patients with newly diagnosed T2DM have
      elevated serum APPL1 levels, suggesting the involvement of APPL1 in the
      development of T2DM.

PMID- 22985588
TI  - [Analysis of infection-related mortality after allogeneic hematopoietic stem cell
      transplantation in patients with refractory/relapse acute leukemia].
AB  - OBJECTIVE: To investigate infection-related mortality (IRM) after allogeneic
      hematopoietic stem cell transplantation in patients with refractory/relapse acute
      leukemia. METHODS: We conducted a retrospective analysis of 127 patients with
      refractory/relapse acute leukemia and investigated the incidence, causes and risk
      factors of IRM. RESULTS: Sixty-seven of the patients died after the
      transplantation. The 5-year overall survival and disease-free survival was
      (35.2?5.3)% and (30.8?5.6)% among these patients, respectively. IRM occurred in
      28.3% (36/127) of the patients. Multivariate analysis showed that grade II-IV
      acute graft-versus-host diseases (aGVDH, P=0.049, OR=3.017) and post-transplant
      invasive fungal infection (P=0.032, OR=3.223) were independent risk factors of
      IRM. CONCLUSION: As a common cause of transplant-related mortality, IRM is more
      frequent in cases of refractory/relapse acute leukemia than in cases with a
      standard risk profile, and effective prophylaxis and treatment of severe GVHD
      remain currently the primary measures for reducing post-transplant IRM.

PMID- 22985589
TI  - [Peripheral T-cell lymphoma-unspecified with intestinal and liver involvement
      besides the lymph nodes: a case report].
AB  - The majority of intestinal lymphoma is derived from B cells, and peripheral T
      cell lymphoma-unspecified (PTCL-U) rarely invades the intestines and liver. We
      report a case of PTCL-U that invaded also the intestines and liver besides the
      lymph nodes, characterized by multiple irregular ulcers of the intestine and
      ileocecal junction, and multiple intrahepatic low density foci. The diagnosis was
      established by mucosal biopsy and pathological examination. This case highlights
      the possibility of PTCL-U involving uncommon organs, for which a definite
      diagnosis has to be established pathologically. PTCL-U is highly malignant with a
      poor prognosis, and so far no standard treatment strategy has been available.

PMID- 22985590
TI  - Production and partial characterization of bioemulsifier from a chromium
      resistant actinobacteria.
AB  - Surface-active compounds such as synthetic emulsifiers have been used for several
      decades, both for the degradation of hydrocarbons and increasing desorption of
      soil-bound metals. However, due to their high toxicity, low degradability, and
      production costs unaffordable for use in larger ecosystems, synthetic emulsifiers
      have been gradually replaced by those derived from natural sources such as plants
      or microbes. In previous studies, the bacterium Streptomyces sp. MC1 has shown
      the ability to reduce and/or accumulate Cr(VI), a highly promising advance in the
      development of methods for environmental clean-up of sites contaminated with
      chromium. Here, new studies on the production of emulsifier from this strain are
      presented. The cultivation factors that have a significant influence on
      emulsifier biosynthesis, as well as the interactions among them, were studied by
      factorial design. Based upon optimization studies, maximum bioemulsifier
      production was detected in the culture medium having an initial pH of 8 with
      phosphate 2.0 g L(-1) and Ca(+2) 1.0 g L(-1) added, with an emulsification index
      about 3.5 times greater compared to the basal value. Interestingly, in the
      presence of 5.0 g L(-1) Cr(VI), Streptomyces sp. MC1 retained about 65% of its
      emulsifier production ability. Partially purified emulsifier presented high
      thermo-stability and partial water solubility. These findings could have
      promising future prospects for the remediation of organic- and metal-contaminated
      sites.

PMID- 22985591
TI  - Evaluation of biodegradability of phenol and bisphenol A during mesophilic and
      thermophilic municipal solid waste anaerobic digestion using 13C-labeled
      contaminants.
AB  - In this paper, the isotopic tracing using (13)C-labeled phenol and bisphenol A
      was used to study their biodegradation during anaerobic digestion of municipal
      solid waste. Microcosms were incubated anaerobically at 35  degrees C (mesophilic
      conditions) and 55  degrees C (thermophilic conditions) without steering. A
      continuous follow-up of the production of biogas (CH(4) and CO(2)), was carried
      out during 130 d until the establishment of stable methanogenesis. Then (13)C(12)
      BPA, and (13)C(6)-phenol were injected in microcosms and the follow-up of their
      degradation was performed simultaneously by gas chromatography isotope-ratio mass
      spectrometry (GC-IRMS) and gas chromatography mass spectrometry (GC-MS).
      Moreover, Carbon-13 Nuclear Magnetic Resonance ((13)C-NMR) Spectroscopy is used
      in the identification of metabolites. This study proves that the mineralization
      of phenol to CO(2) and CH(4) occurs during anaerobic digestion both in mesophilic
      and thermophilic conditions with similar kinetics. In mesophilic condition phenol
      degradation occurs through the benzoic acid pathway. In thermophilic condition it
      was not possible to identify the complete metabolic pathway as only acetate was
      identified as metabolite. Our results suggest that mineralization of phenol under
      thermophilic condition is instantaneous explaining why metabolites are not
      observed as they do not accumulate. No biodegradation of BPA was observed.

PMID- 22985592
TI  - Brominated flame retardants and dechloranes in eels from German Rivers.
AB  - The levels of PBDEs, alternate BFRs and dechloranes in European Eel (Anguilla
      anguilla) samples (elvers, yellow and silver eels) were investigated to compare
      the contamination of eels from the rivers Elbe and Rhine and to estimate the BFR
      contamination throughout the eel's life cycle. PBDEs were the dominating flame
      retardants (FRs) in muscle tissues of yellow and silver eels, while the alternate
      BFR 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) and the Dechlorane 602
      were the dominating FRs in elvers (juvenile eels). Concentrations of FRs in
      silver eels from river Rhine were generally higher than concentrations in other
      eels analysed with up to 46 ng g(-1) wet weight (ww) ?PBDEs. The concentrations
      in yellow and silver eels from river Elbe were similar with an average of 9.0+/
      5.1 ng g(-1)ww and 8.1+/-3.7 ng g(-1)ww respectively. PBDE concentrations in
      elvers were comparably low (0.02 (BDE-100) to 0.1 (BDE-183) ng g(-1)ww), which
      lead to the conclusion that these contaminants were mostly ingested within the
      rivers. Among the alternate BFRs and dechloranes, DPTE as well as the Dechlorane
      602 and Dechlorane Plus (DP) were found in all life cycle stages and rivers with
      concentrations between 0.01 ng g(-1)ww and 0.7 ng g(-1)ww. Dechlorane 603 could
      only be detected in silver eels from river Rhine. Pentabromoethylbenzene (PBEB)
      was only found in yellow and silver eels and bis(2-ethylhexyl)tetrabromophthalate
      (BEHTBP) could only be detected in elvers. These are the first reports of Dec-602
      and 603 in aquatic organisms from Europe. The results of this study show the
      lasting relevance of PBDEs as contaminants in rivers and river-dwelling species
      but also the growing relevance of emerging contaminants such as alternate BFRs
      and dechloranes.

PMID- 22985593
TI  - Interaction of silver nanoparticles with pure nitrifying bacteria.
AB  - In this study, Nitrosomonas europaea ATCC 19718 was exposed to silver
      nanoparticles (AgNPs) of different particle size (7+/-3 and 40+/-14nm) and
      different coatings (polyvinyl alcohol and adenosine triphosphate disodium). For
      all different AgNPs used in the study, large aggregates were gradually formed
      after addition of AgNPs into the media containing N. europaea. The scanning
      electron microscopy and energy dispersive X-ray spectroscopy of the
      microstructures suggested that bacterial cells and electrolytes had significant
      effects on AgNP aggregation. Size- and coating-dependent inhibition of ammonia
      oxidation by AgNPs was observed, and our analysis suggested that the inhibition
      was not only due to the released dissolved silver, but also the dispersity of
      AgNPs in the culture media. Electron microscopy images showed AgNPs could cause
      the damage of cell wall of N. europaea and make the nucleoids disintegrated and
      condensed next to cell membrane. Surface-enhanced Raman scattering signals also
      implied the damage of cell membrane caused by AgNPs. Further protein expression
      analysis revealed that AgNPs would inhibit important protein functions, including
      biosynthesis, gene expression, energy production and nitrification to further
      cause toxicity to N. europaea. Our findings explain the susceptibility of N.
      europaea to inhibition by AgNPs and the possible interaction between each other.
      Future research is needed to characterize these effects in more complex cultures
      and media such as activated sludge and wastewater.

PMID- 22985594
TI  - A double layer model of the gas bubble/water interface.
AB  - Zeta potential is a physico-chemical parameter of particular importance to
      describe sorption of contaminants at the surface of gas bubbles. Nevertheless,
      the interpretation of electrophoretic mobilities of gas bubbles is complex. This
      is due to the specific behavior of the gas at interface and to the excess of
      electrical charge at interface, which is responsible for surface conductivity. We
      developed a surface complexation model based on the presence of negative surface
      sites because the balance of accepting and donating hydrogen bonds is broken at
      interface. By considering protons adsorbed on these sites followed by a diffuse
      layer, the electrical potential at the head-end of the diffuse layer is computed
      and considered to be equal to the zeta potential. The predicted zeta potential
      values are in very good agreement with the experimental data of H(2) bubbles for
      a broad range of pH and NaCl concentrations. This implies that the shear plane is
      located at the head-end of the diffuse layer, contradicting the assumption of the
      presence of a stagnant diffuse layer at the gas/water interface. Our model also
      successfully predicts the surface tension of air bubbles in a KCl solution.

PMID- 22985595
TI  - A simple and rapid fluorescent neuraminidase enzymatic assay on a microfluidic
      chip.
AB  - Neuraminidase enzymatic assay is an inexpensive, reliable, and quick method of
      detecting viruses. However, the assay in conventional laboratories requires a
      large amount of samples and reagents and multiple steps, which makes the
      conventional assay labor intensive and time consuming. This article reports a
      novel and simple method for conducting the neuraminidase enzymatic assay on a
      microfluidic chip. By using 4-methylumbelliferyl-N-acetyl-alpha-d-neuraminic acid
      as the fluorescent substrate and applying an electric field, the newly developed
      assay is simple, fast, and automatic. Fluorescence of the enzymatic reaction
      product was recorded as the assay result, and the fluorescence intensity
      quantitatively indicates the concentration of the sample, which proves that the
      novel assay on a microfluidic chip has a potential to be developed into a
      portable device for on-site detection of environmental samples.

PMID- 22985596
TI  - [Physical activity and aging: opposing physiologic effects].
AB  - The benefits of physical activity in preventing premature mortality have been
      established by a large set of epidemiological studies. These benefits have been
      shown both in middle-aged and elderly individuals. Furthermore, the reduction of
      acute events such as myocardial infarction observed with higher levels of
      physical activity together with the increase in disease-free life expectancy
      among the most active individuals supports physical activity's antiaging effect.
      This review highlights two models supporting this effect. The first model
      describes the path to frailty and the second explains that immobilization is a
      stressor which triggers stress-responses responsible for many chronic diseases.
      Aging reduces the physiological reserve and can lead to frailty when this reserve
      cannot allow an appropriate adaptation of the aging body to environmental
      challenges. The components of this physiological reserve can easily be measured
      by cardiorespiratory testing. Among them are heart rate reserve and VO(2)max, the
      maximal body oxygen consumption. The opposite effects of exercise training and
      aging on the physiological reserve are detailed. Sedentary lifestyle accelerates
      the effects of aging in susceptible individuals. Sedentary lifestyle induces
      mechanisms which lead to risk factors of chronic diseases and, eventually, to
      premature death. These inappropriate mechanisms and their consequences constitute
      the sedentary lifestyle syndrome.

PMID- 22985597
TI  - Embolic middle cerebral artery occlusion model using thrombin and fibrinogen
      composed clots in rat.
AB  - Ischemic stroke accounts for over 80% in total human stroke which mostly affect
      middle cerebral artery (MCA) territory. Embolic stroke models induced by
      injection of homologous clots into the internal carotid artery and MCA closely
      mimic human stroke and have been commonly used in stroke research. Studies
      indicate that the size and composition of clots are critical for the
      reproducibility of the stroke model. In the present study, we modified the
      homologous clots formation by addition of thrombin and fibrinogen which produced
      even distribution of fibrin with tight cross linkage of red blood cells. We
      optimized the embolic MCA occlusion model in rats using different size of the
      mixed clots. A precise lodgment of the clots at the MCA bifurcation and highly
      reproducible ischemic lesion in the MCA territory were demonstrated in the
      embolic MCA occlusion model induced by injection of 10 pieces of 1-mm long mixed
      clots made in PE-60 catheter. We further tested the effect of recombinant tissue
      plasminogen activator (rtPA) in this embolic MCA occlusion model. rtPA induced
      thrombolysis, improved neurological outcome, and significantly reduced ischemic
      lesion volume when administered at 1h after embolism as compared with control. In
      summary, we have established a reproducible embolic MCA occlusion model using
      clots made of homologous blood, thrombin and fibrinogen. The mixed clots enable
      precise lodgment at the MCA bifurcation which is responsive to thrombolytic
      therapy of rtPA.

PMID- 22985598
TI  - The [4Fe-4S]-cluster coordination of [FeFe]-hydrogenase maturation protein HydF
      as revealed by EPR and HYSCORE spectroscopies.
AB  - [FeFe] hydrogenases are key enzymes for bio(photo)production of molecular
      hydrogen, and several efforts are underway to understand how their complex active
      site is assembled. This site contains a [4Fe-4S]-2Fe cluster and three conserved
      maturation proteins are required for its biosynthesis. Among them, HydF has a
      double task of scaffold, in which the dinuclear iron precursor is chemically
      modified by the two other maturases, and carrier to transfer this unit to a
      hydrogenase containing a preformed [4Fe-4S]-cluster. This dual role is associated
      with the capability of HydF to bind and dissociate an iron-sulfur center, due to
      the presence of the conserved FeS-cluster binding sequence CxHx(46-53)HCxxC. The
      recently solved three-dimensional structure of HydF from Thermotoga neapolitana
      described the domain containing the three cysteines which are supposed to bind
      the FeS cluster, and identified the position of two conserved histidines which
      could provide the fourth iron ligand. The functional role of two of these
      cysteines in the activation of [FeFe]-hydrogenases has been confirmed by site
      specific mutagenesis. On the other hand, the contribution of the three cysteines
      to the FeS cluster coordination sphere is still to be demonstrated. Furthermore,
      the potential role of the two histidines in [FeFe]-hydrogenase maturation has
      never been addressed, and their involvement as fourth ligand for the cluster
      coordination is controversial. In this work we combined site-specific mutagenesis
      with EPR (electron paramagnetic resonance) and HYSCORE (hyperfine sublevel
      correlation spectroscopy) to assign a role to these conserved residues, in both
      cluster coordination and hydrogenase maturation/activation, in HydF proteins from
      different microorganisms.

PMID- 22985599
TI  - Prokaryotic assembly factors for the attachment of flavin to complex II.
AB  - Complex II (also known as Succinate dehydrogenase or Succinate-ubiquinone
      oxidoreductase) is an important respiratory enzyme that participates in both the
      tricarboxylic acid cycle and electron transport chain. Complex II consists of
      four subunits including a catalytic flavoprotein (SdhA), an iron-sulphur subunit
      (SdhB) and two hydrophobic membrane anchors (SdhC and SdhD). Complex II also
      contains a number of redox cofactors including haem, Fe-S clusters and FAD, which
      mediate electron transfer from succinate oxidation to the reduction of the mobile
      electron carrier ubiquinone. The flavin cofactor FAD is an important redox
      cofactor found in many proteins that participate in oxidation/reduction
      reactions. FAD is predominantly bound non-covalently to flavoproteins, with only
      a small percentage of flavoproteins, such as complex II, binding FAD covalently.
      Aside from a few examples, the mechanisms of flavin attachment have been a
      relatively unexplored area. This review will discuss the FAD cofactor and the
      mechanisms used by flavoproteins to covalently bind FAD. Particular focus is
      placed on the attachment of FAD to complex II with an emphasis on SdhE (a
      DUF339/SDH5 protein previously termed YgfY), the first protein identified as an
      assembly factor for FAD attachment to flavoproteins in prokaryotes. The molecular
      details of SdhE-dependent flavinylation of complex II are discussed and
      comparisons are made to known cofactor chaperones. Furthermore, an evolutionary
      hypothesis is proposed to explain the distribution of SdhE homologues in
      bacterial and eukaryotic species. Mechanisms for regulating SdhE function and how
      this may be linked to complex II function in different bacterial species are also
      discussed. This article is part of a Special Issue entitled: Respiratory complex
      II: Role in cellular physiology and disease.

PMID- 22985601
TI  - The cytosol-synthesized subunit II (Cox2) precursor with the point mutation W56R
      is correctly processed in yeast mitochondria to rescue cytochrome oxidase.
AB  - Deletion of the yeast mitochondrial gene COX2 encoding subunit 2 (Cox2) of
      cytochrome c oxidase (CcO) results in loss of respiration (Deltacox2 strain).
      Supekova et al. (2010) [1] transformed a Deltacox2 strain with a vector
      expressing Cox2 with a mitochondrial targeting sequence (MTS) and the point
      mutation W56R (Cox2(W56R)), restoring respiratory growth. Here, the CcO carrying
      the allotopically-expressed Cox2(W56R) was characterized. Yeast mitochondria from
      the wild-type (WT) and the Deltacox2+Cox2(W56R) strains were subjected to Blue
      Native electrophoresis. In-gel activity of CcO and spectroscopic quantitation of
      cytochromes revealed that only 60% of CcO is present in the complemented strain,
      and that less CcO is found associated in supercomplexes as compared to WT. CcOs
      from the WT and the mutant exhibited similar subunit composition, although
      activity was 20-25% lower in the enzyme containing Cox2(W56R) than in the one
      with Cox2(WT). Tandem mass spectrometry confirmed that W(56) was substituted by
      R(56) in Cox2(W56R). In addition, Cox2(W56R) exhibited the same N-terminus than
      Cox2(WT), indicating that the MTS of Oxa1 and the leader sequence of 15 residues
      were removed from Cox2(W56R) during maturation. Thus, Cox2(W56R) is identical to
      Cox2(WT) except for the point mutation W56R. Mitochondrial Cox1 synthesis is
      strongly reduced in Deltacox2 mutants, but the Cox2(W56R) complemented strain led
      to full restoration of Cox1 synthesis. We conclude that the cytosol-synthesized
      Cox2(W56R) follows a rate-limiting process of import, maturation or assembly that
      yields lower steady-state levels of CcO. Still, the allotopically-expressed
      Cox2(W56R) restores CcO activity and allows mitochondrial Cox1 synthesis to
      advance at WT levels.

PMID- 22985602
TI  - Controlled release of rasagiline mesylate promotes neuroprotection in a rotenone
      induced advanced model of Parkinson's disease.
AB  - Microencapsulation of rasagiline mesylate (RM) into PLGA microspheres was
      performed by method A (O/W emulsion) and method B (W/O/W double emulsion). The
      best formulation regarding process yield, encapsulation efficiency and in vitro
      drug release was that prepared with method A, which exhibited constant drug
      release for two weeks (K(0)=62.3 MUg/day/20mg microspheres). Exposure of SKN-AS
      cells to peroxide-induced oxidative stress (1 mM) resulted in cell apoptosis
      which was significantly reduced by RM (40.7-102.5 MUM) as determined by cell
      viability, ROS production and DNA fragmentation. Daily doses of rotenone (2
      mg/kg) given i.p. to rats for 45 days induced neuronal and behavioral changes
      similar to those occurring in PD. Once an advanced stage of PD was achieved,
      animals received RM in saline (1 mg/kg/day) or encapsulated within PLGA
      microspheres (amount of microspheres equivalent to 15 mg/kg RM given on days 15
      and 30). After 45 days RM showed a robust effect on all analytical outcomes
      evaluated with non-statistically significant differences found between its
      administration in solution or within microparticles however; with this controlled
      release system administration of RM could be performed every two weeks thereby
      making this new therapeutic system an interesting approach for the treatment of
      PD.

PMID- 22985603
TI  - Ability of fibrinogen gamma-derived dodecapeptides with different sequences to
      bind to rat platelets.
AB  - A dodecapeptide (gamma400-411) derived from a fibrinogen gamma-chain carboxyl
      terminal sequence recognizes specifically the active form of GPIIb/IIIa on the
      surface of activated platelets. For the purpose of efficient hemostasis, we
      previously developed ADP-encapsulated liposomes modified with human-dodecapeptide
      (HHLGGAKQAGDV, human-H12). On the other hand, the amino-acid sequence of H12 from
      rats is HHMGGSKQVGDM, having only 67% homology to that from humans. Here, we
      investigated the ability of rat-H12 in comparison with human-H12 to bind to
      platelets. Firstly, rat platelets were activated with phorbol-12-myristate-13
      acetate (PMA), and the activation was confirmed by flow cytometry. Next, we
      evaluated the dissociation constant (K(d)) of human-H12 and rat-H12 for
      dissociation from rat platelets by using FACS. As a result, the K(d) of human-H12
      and rat-H12 with respect to rat platelets was 2.78 +/- 0.21 and 2.91 +/- 0.22
      MUM, respectively. Furthermore, H12 from both species inhibited quite similarly
      the aggregation of rat platelets in platelet-rich plasma (PRP). These results
      suggest that H12 from different species with different amino acid sequences
      interacts similarly with GPIIb/IIIa on platelets.

PMID- 22985600
TI  - Design and use of photoactive ruthenium complexes to study electron transfer
      within cytochrome bc1 and from cytochrome bc1 to cytochrome c.
AB  - The cytochrome bc1 complex (ubiquinone:cytochrome c oxidoreductase) is the
      central integral membrane protein in the mitochondrial respiratory chain as well
      as the electron-transfer chains of many respiratory and photosynthetic
      prokaryotes. Based on X-ray crystallographic studies of cytochrome bc1, a
      mechanism has been proposed in which the extrinsic domain of the iron-sulfur
      protein first binds to cytochrome b where it accepts an electron from ubiquinol
      in the Qo site, and then rotates by 57 degrees  to a position close to cytochrome
      c1 where it transfers an electron to cytochrome c1. This review describes the
      development of a ruthenium photooxidation technique to measure key electron
      transfer steps in cytochrome bc1, including rapid electron transfer from the iron
      sulfur protein to cytochrome c1. It was discovered that this reaction is rate
      limited by the rotational dynamics of the iron-sulfur protein rather than true
      electron transfer. A conformational linkage between the occupant of the Qo
      ubiquinol binding site and the rotational dynamics of the iron-sulfur protein was
      discovered which could play a role in the bifurcated oxidation of ubiquinol. A
      ruthenium photoexcitation method is also described for the measurement of
      electron transfer from cytochrome c1 to cytochrome c. This article is part of a
      Special Issue entitled: Respiratory Complex III and related bc complexes. 

PMID- 22985604
TI  - Application of maximum bubble pressure surface tensiometer to study protein
      surfactant interactions.
AB  - Binding of a surfactant to proteins can affect their physicochemical stability
      and solubility in a formulation. The extent of the effect depends on the binding
      stoichiometry. In this study, we have utilized the technique of maximum bubble
      pressure surface tensiometry to characterize the binding between human serum
      albumin (HSA) and surfactants (sodium dodecyl sulfate (SDS) and polysorbate 80)
      by dynamic surface tension measurements. Results show that two classes of binding
      sites are present in HSA for SDS, 5 primary binding sites with high binding
      affinity (K(a)=5.38*10(5) M(-1)) and 12 secondary binding sites with low affinity
      (K(a)=6.7*10(4) M(-1)). The binding is high affinity and limited capacity due to
      both, ionic and hydrophobic interactions between HSA and SDS. For polysorbate 80,
      the binding does not follow the Scatchard plot, and is low affinity and high
      capacity, indicating that polysorbate 80 interacts with HSA through hydrophobic
      interactions. The results show that maximal bubble pressure surface tensiometry
      is a fast and convenient technique to determine the concentration of free and
      bound surfactants in the presence of proteins.

PMID- 22985605
TI  - Effects of exogenous oxytocin on uterine blood flow in puerperal dairy cows: the
      impact of days after parturition and retained fetal membranes.
AB  - The objective of this study was to examine whether an oxytocin challenge test
      (OCT), evaluated by measuring the changes in uterine blood flow using transrectal
      colour Doppler ultrasonography, is a suitable non-invasive method to determine
      uterine contractility in puerperal dairy cows. The changes in uterine blood flow
      during uterine contractions induced by oxytocin were evaluated on days 2 and 5
      postpartum (pp). Twelve clinically healthy Holstein cows were randomly assigned
      into two groups: (1) oxytocin group (n=7), 50 IU oxytocin injected IM and (2)
      control group (n=5), 5 mL saline injected IM. Blood flow volume (BFV) and
      pulsatility index (PI) in the uterine arteries were determined before and after
      injection for 120 min on days 2 and 5 pp. BFV declined and PI increased rapidly
      after oxytocin injection on day 2 (P<0.05), whereas oxytocin on day 5 pp did not
      cause changes in blood flow parameters. The result confirmed that uterine
      responsiveness to oxytocin decreases with time postpartum in healthy cows. The
      same OCT was applied in cows with retained fetal membranes (n=6) on day 2 pp,
      however uterine blood flow showed no change after oxytocin injection. The results
      showed that an OCT on day 2 pp may be a useful method for investigating the
      uterine contractile response to oxytocin (reflected as the decrease of uterine
      blood flow) and the potential pathophysiology of uterine involution in cows.

PMID- 22985606
TI  - The impact of dystocia on dairy calf health, welfare, performance and survival.
AB  - Up to one-third of dairy calves are born after dystocia and this is a major cause
      of calf mortality. This study investigated the neonatal physiology, survival,
      health and subsequent growth of dairy calves following dystocia and is the first
      longitudinal study to analyse multiple effects and to look beyond the perinatal
      period. A total of 455 live born Holstein calves (N: No assistance, n=360; FN:
      Farmer assistance but normally presented calf, n=82; FM: Farmer assistance of
      malpresented calf, n=13) were followed from birth to first service (heifers) or
      until leaving the farm (bulls). Compared to N calves, FN and FM animals had
      higher salivary cortisol concentrations at day 1 (P<0.001) and FN calves had
      lower passive immune transfer (P=0.03). Dystocia had no biologically significant
      impact on rectal temperature throughout the first 4 days (P>0.05). During the
      first 60 days, FM calves had a higher proportion of days with non-routine health
      treatments (P<0.05) and, by the time of weaning, mortality in FN and FM heifers
      was higher than in N calves (2.8*; P<0.01). However, in surviving calves, growth
      to first service was not affected by dystocia category (P>0.05). Calves which
      survive dystocia experience lower passive immunity transfer, higher mortality and
      higher indicators of physiological stress. Such calves have poorer welfare in the
      neonatal period and possibly beyond. Strategies need to be implemented to improve
      the subsequent health and welfare of such calves and to lower the incidence of
      dystocia.

PMID- 22985607
TI  - Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of
      patients with porphyria cutanea tarda.
AB  - BACKGROUND & AIMS: Porphyria cutanea tarda (PCT) is an iron-related disorder
      caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be
      treated by phlebotomy or low doses of hydroxychloroquine. We performed a
      prospective pilot study to compare the efficacy and safety of these therapies.
      METHODS: We analyzed data from 48 consecutive patients with well-documented PCT
      to characterize susceptibility factors; patients were treated with phlebotomy
      (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low
      dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month
      after they had normal plasma levels of porphyrin). We compared the time required
      to achieve a normal plasma porphyrin concentration (remission, the primary
      outcome) for 17 patients treated with phlebotomy and 13 treated with
      hydroxychloroquine. RESULTS: The time to remission was a median 6.9 months for
      patients who received phlebotomy and 6.1 months for patients treated with
      hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a
      difference that was not significant (log-rank, P = .06 and P = .95,
      respectively). The sample size was insufficient to confirm noninferiority of
      hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95
      5.06) for all patients. Patients who received hydroxychloroquine had
      substantially better compliance. There were no significant side effects of either
      treatment. CONCLUSIONS: Hydroxychloroquine, 100 mg twice weekly, is as effective
      and safe as phlebotomy in patients with PCT, although noninferiority was not
      established. Given these results, higher-dose regimens of hydroxychloroquine,
      which have more side effects, do not seem justified. Compliance was better and
      projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long
      term studies are needed to compare durability of response. ClinicalTrials.gov
      number, NCT01573754.

PMID- 22985609
TI  - Advantages of functional single-cell isolation method over standard agar plate
      dilution method as a tool for studying denitrifying bacteria in rice paddy soil.
AB  - We recently established a method for isolating functional single cells from
      environmental samples using a micromanipulator (Functional single-cell (FSC)
      isolation), and applied it to the study of denitrifying bacteria in rice paddy
      soil (Ashida et al. 2010. Appl Microbiol Biotechnol 85:1211-1217). To further
      examine the advantages and possible disadvantages of the FSC method, we isolated
      denitrifying bacteria from the same rice paddy soil sample using both FSC and
      standard agar plate dilution (APD) methods and compared in this study. The
      proportion of denitrifying bacteria in the total isolates was more than 6-fold
      larger with FSC isolation (57.1%) compared with the APD method (9.2%).
      Denitrifying bacteria belonging to Alphaproteobacteria and Bacilli were commonly
      isolated using both methods, whereas those belonging to Betaproteobacteria, which
      had been found to be active in the denitrification-inductive paddy soil, were
      isolated only with the FSC method. On the other hand, Actinobacteria were only
      isolated using the APD method. The mean potential denitrification activity of the
      FSC isolates was higher than that of the APD isolates. Overall, FSC isolation was
      confirmed to be an excellent method for studying denitrifying bacteria compared
      with the standard agar plate dilution method.

PMID- 22985608
TI  - Variation of adenoma prevalence by age, sex, race, and colon location in a large
      population: implications for screening and quality programs.
AB  - BACKGROUND & AIMS: Reliable community-based colorectal adenoma prevalence
      estimates are needed to inform colonoscopy quality standards and to estimate
      patient colorectal cancer risks; however, minimal data exist from populations
      with large numbers of diverse patients and examiners. METHODS: We evaluated the
      prevalence of adenomas detected by sex, age, race/ethnicity, and colon location
      among 20,792 Kaiser Permanente Northern California members >=50 years of age who
      received a screening colonoscopy examination (102 gastroenterologists, 2006
      2008). RESULTS: Prevalence of detected adenomas increased more rapidly with age
      in the proximal colon (adjusted odds ratio [OR], 2.39; 95% confidence interval
      [CI], 2.05-2.80; 70-74 vs 50-54 years) than in the distal colon (OR, 1.89; 95%
      CI, 1.63-2.19). Prevalence was higher among men vs women at all ages (OR, 1.77;
      95% CI, 1.66-1.89), increasing in men from 25% to 39% at >=70 years and in women
      from 15% at 50-54 years to 26% (P < .001). Proximal adenoma prevalence was higher
      among blacks than whites (OR, 1.26; 95% CI, 1.04-1.54), although total prevalence
      was similar, including persons <60 years old (OR, 1.17; 95% CI, 0.91-1.50).
      CONCLUSIONS: Prevalence of detected adenomas increases substantially with age and
      is much higher in men; proximal adenomas are more common among blacks than
      whites, although the total prevalence and the prevalence for ages <60 years were
      similar by race. These demographic differences are such that current adenoma
      detection guidelines may not be valid, without adjustment, for comparing
      providers serving different populations. The variation in prevalence and location
      may also have implications for the effectiveness of screening methods in
      different demographic groups.

PMID- 22985610
TI  - Short-duration oral amiodarone for prevention of atrial fibrillation post heart
      surgery.
AB  - BACKGROUND: Atrial fibrillation occurs in 20% to 40% of patients post cardiac
      surgery. Prophylactic amiodarone decreases the incidence of atrial fibrillation,
      especially in those not taking beta-blockers. Studies, however, vary in dosage,
      duration of treatment, and route of administration. Limited studies evaluating
      short duration use of oral amiodarone show conflicting results. We hypothesize
      that an order set for use of short duration, oral amiodarone started the night
      before surgery and continued for 4 to 6 days will decrease atrial fibrillation
      after heart surgery. METHODS: The Society of Thoracic Surgeons database was used
      to identify 471 patients who received amiodarone per order set and 151 patients
      that did not receive amiodarone. The amiodarone order set included amiodarone 600
      mg the night before surgery and 400mg twice daily for 4 to 6 days post heart
      surgery. After propensity matching, 112 patients remained in each group. We
      compared outcomes for the 2 groups as a case-controlled, retrospective, study.
      RESULTS: Atrial fibrillation occurred in 43% (48 of 112) of the patients that did
      not receive amiodarone vs 23% (26 of 112) receiving prophylactic amiodarone
      (P=<.001). There was no increased incidence of hemodynamic, pulmonary, or other
      adverse outcomes observed between the 2 groups. CONCLUSIONS: This practical order
      set for, short duration, oral amiodarone, with or without adjunct beta-blocker
      therapy started the night before heart surgery and continued for up to six days
      post surgery, appears to be a safe and effective treatment for reducing the
      incidence of atrial fibrillation following heart surgery.

PMID- 22985611
TI  - Vanishing testes: a literature review.
AB  - Vanishing testes syndrome is often referred to as testicular regression syndrome
      (TRS) in the recent medical literature. The most characteristic histological
      findings are presence of a fibrovascular nodule with associated hemosiderin-laden
      macrophages and dystrophic calcification. Residual testicular tubules are found
      in less than 10% of cases, with prevalence being unrelated to age at surgery.
      Presence of seminiferous tubules and viable germ cells in testicular remnant
      tissue has been reported in some series. TRS theoretically carries a potential
      for malignant degeneration in the long term and therefore removal of any remnant
      is a common practice to eliminate this risk. However, no case series has reported
      germinal dysplasia or intratubular germ cell neoplasia in any of the specimens
      taken from these patients.

PMID- 22985612
TI  - Long-term efficacy of insulin pump therapy in children with type 1 diabetes
      mellitus.
AB  - OBJECTIVE: Insulin pumps have been well established for insulin delivery.
      However, questions about long-term efficacy of insulin pump therapy still remain.
      We evaluated the long-term efficacy of continuous insulin infusion pump therapy
      (CSII) in pediatric patients with type 1 diabetes mellitus (T1DM). METHODS: This
      was a retrospective observational study which included 131 patients with T1DM who
      transitioned to an insulin pump from multiple daily insulin (MDI) injections
      between 1999 and 2009 and were followed by one endocrinologist. Data were
      collected from 6 months prior to switching to CSII to 30 months after initiation
      of CSII and included glycated hemoglobin (HbA1c) and insulin requirement. Of the
      131 patients, 45 had complete data consisting of a visit and HbA1c every 6 months
      for 30 months after transition to CSII and were included for analysis. RESULTS:
      Mean HbA1c prior to starting the CSII was 8.0 +0.9 %, 7.7 +1.0 % at 6 months and
      7.8+1.2 % at 1 yr post initiation of CSII. However, at 30 months, HbA1c increased
      to 8.0+1.3%. A trend in transient improvement in HbA1c was limited only to those
      patients >11 yr of age and those requiring >0.75 u/kg/day of insulin at
      transition and was not seen in those <11 yr of age or those requiring <0.75
      u/kg/day and did not persist beyond 1 year. CONCLUSIONS: There was no long-term
      significant difference in glycemic control in patients with CSII as compared to
      MDI.

PMID- 22985613
TI  - Is premature thelarche in the first two  years of life transient?
AB  - OBJECTIVE: Premature thelarche (PT) refers to isolated onset of thelarche in
      girls younger than 8 years of age. Most cases have an onset under 2 years of age.
      We aimed to establish whether the onset of thelarche under 2 years of age
      certifies a transient clinical course, as suggested by several authors. METHODS:
      Sixty-seven girls with an onset of PT under 2 years of age were classified as
      having early puberty (EP) or classical PT after one year of follow-up.
      Progression of pubertal findings or absolute growth velocity (GV) standard
      deviation score (SDS) above 1 SDS constituted the criteria for a diagnosis of EP.
      RESULTS: Twenty (29.1%) girls were classified as having EP and 47 (70.1%) girls
      as having classical PT. Basal serum luteinizing hormone (LH; ICMA) values at a
      cut-off level of 0.3 IU/L were found to be a significant risk factor for having
      an atypical course [OR=7.8; CI (95%): 2.04-30.4, p=0.003]. CONCLUSIONS: Onset of
      thelarche under 2 years of age does not assure a transient course in a remarkable
      proportion of girls with PT. An absolute GV value of >1 SDS or a basal LH level
      >=0.3 IU/L are suggested as indicators for close follow-up.

PMID- 22985615
TI  - Iatrogenic Cushing's syndrome following short-term intranasal steroid use.
AB  - Cushing's syndrome (CS) is common after oral steroid use and has also been
      reported following topical or inhaled use, but it is extremely uncommon after
      intranasal administration. In this paper, we present the case of a child who
      developed CS after intranasal application of combined moxifloxacin-dexamethasone
      eye drops for epistaxis for a period of 3 months. CS caused by ocular
      preparations of steroids has not been reported previously. This case report
      highlights the fact that even eye drops can contain high doses of steroids and
      can lead to CS especially in children and especially if used intranasally. Ocular
      steroid drops should not be used intranasally. To minimize gastrointestinal
      absorption and therefore the risk of CS, nasal sprays should be preferred over
      nasal drops for intranasal steroid application.

PMID- 22985614
TI  - Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor
      pathway inhibitor and thrombomodulin levels in children with hypothyroidism.
AB  - OBJECTIVE: We determined the profile of coagulation/fibrinolytic and vascular
      endothelial cell function parameters including plasminogen activator inhibitor
      (PAI) and thrombin-activatable fibrinolysis inhibitor (TAFI), tissue factor
      pathway inhibitor (TFPI), thrombomodulin (TM), and tissue plasminogen activator
      (tPA) levels in children with hypothyroidism. METHODS: Forty children with
      hypothyroidism aged 0-16 months who presented for the first time to our hospital
      and 29 age-and sex-matched healthy controls were enrolled in the study. All
      coagulation tests were performed with ELISA method. One year after Na-L-thyroxine
      treatment, the study parameters were re-evaluated in 25 euthyroid children out of
      the 40 patients diagnosed with hypothyroidism. RESULTS: Although no significant
      effect was detected regarding PAI antigen (Ag) and tPA Ag, the levels of TAFI,
      TM, and TFPI were consistent with subclinical hypercoagulability and
      hypofibrinolysis. There was a significant increase in TAFI Ag levels and a
      significant decrease in TFPI Ag and TM Ag levels in hypothyroid patients compared
      to healthy controls. As a result of correlation tests, the largest impact of
      hypothyroidism on coagulation system was on TFPI. In accordance with these
      findings, TAFI Ag levels decreased and TFPI Ag and TM Ag levels increased with
      hormonal replacement therapy. CONCLUSIONS: Increased TAFI and decreased TFPI and
      TM in patients with hypothyroidism may indicate a potential hypercoagulable and
      hypofibrinolytic state as well as possible endothelial dysfunction, which may
      increase the risk of atherosclerotic and atherothrombotic complications. Thyroid
      hormone levels should also be checked in patients with a predisposition to
      coagulation, and thyroid replacement therapy should be initiated.

PMID- 22985616
TI  - McCune-Albright syndrome mimicking malignancy: an endocrine disease from
      oncologist's perspective.
AB  - Fibrous dysplasia (FD) is categorized as either monostotic or polyostotic and may
      occur as a component of McCune-Albright syndrome (MAS). Imaging findings can
      mimic neoplastic diseases. We present a case of MAS initially suspected to have
      neoplastic disease. A 9-year-old girl was admitted to pediatric emergency with
      ataxia. Upon hospitalization, an extradural mass was seen on cranial magnetic
      resonance imaging (MRI) and the bone survey showed lytic lesions in the long
      bones. The patient was referred to the pediatric oncology department with a
      presumptive diagnosis of Langerhans cell histiocytosis or metastatic tumor.
      Further investigations demonstrated that the patient had MAS and coexisting
      postinfectious cerebellitis. The findings in this patient demonstrate that the
      radiographic findings and the clinical presentation of FD and MAS may be similar
      to those of malignant diseases.

PMID- 22985617
TI  - Isolated Cushing's syndrome in early infancy due to left adrenal adenoma: an
      unusual aetiology.
AB  - Bilateral macronodular adrenocortical disease as a part of McCune Albright
      Syndrome (MAS) is the most common cause of endogenous Cushing's syndrome (CS) in
      infancy. Adrenocortical tumors causing CS in infancy are extremely rare. We
      report the case of a girl with CS who presented at age 4 months with obesity and
      growth retardation. Her 8 am paired cortisol and adrenocorticotropic hormone
      levels were 49.3 ug/dL and <1 pg/mL, respectively with non-suppressed serum
      cortisol (41 ug/dL) on high-dose dexamethasone suppression test. Abdominal
      computed tomography scan demonstrated a 5.3x4.8x3.7 cm homogenous left adrenal
      mass with distinct borders. Laparotomy following pre-operative stabilization with
      ketoconazole 200 mg/day, revealed a 7.5x5x4 cm lobulated left adrenal mass with
      intact capsule and weighing 115 grams. Histopathology showed small round adrenal
      tumor cells with increased nucleo-cytoplasmic ratio and prominent nucleoli. The
      cells were separated by fibrous septae without any evidence of vascular or
      capsular invasion- findings consistent with adrenal adenoma. On the 8th post
      operative day, after withholding hydrocortisone supplementation, the 8 am
      cortisol level was <1 ug/dL, suggestive of biochemical remission of CS. The
      patient improved clinically with a 7.5 kg weight loss over the next 3.5 months.
      This is perhaps the youngest ever reported infant with CS due to adrenal adenoma.
      Lack of clinical and biochemical evidence of hyperandrogenism as well as the
      benign histology in spite of the large tumor size (>7 cm diameter; 115 g) are
      some of the unique features of our patient.

PMID- 22985618
TI  - Disaster metrics: quantitative estimation of the number of ambulances required in
      trauma-related multiple casualty events.
AB  - INTRODUCTION: Estimating the number of ambulances needed in trauma-related
      Multiple Casualty Events (MCEs) is a challenging task. HYPOTHESIS/PROBLEM:
      Emergency medical services (EMS) regions in the United States have varying "best
      practices" for the required number of ambulances in MCE, none of which is based
      on metric criteria. The objective of this study was to estimate the number of
      ambulances required to respond to the scene of trauma-related MCE in order to
      initiate treatment and complete the transport of critical (T1) and moderate (T2)
      patients. The proposed model takes into consideration the different transport
      times and capacities of receiving hospitals, the time interval from injury
      occurrence, the number of patients per ambulance, and the pre-designated time
      frame allowed from injury until the transfer care of T1 and T2 patients. METHODS:
      The main theoretical framework for this model was based on prehospital time
      intervals described in the literature and used by EMS systems to evaluate
      operational and patient care issues. The North Atlantic Treaty Organization
      (NATO) triage categories (T1-T4) were used for simplicity. RESULTS: The minimum
      number of ambulances required to respond to the scene of an MCE was modeled as
      being primarily dependent on the number of critical patients (T1) present at the
      scene any particular time. A robust quantitative model was also proposed to
      dynamically estimate the number of ambulances needed at any time during an MCE to
      treat, transport and transfer the care of T1 and T2 patients. CONCLUSION: A new
      quantitative model for estimation of the number of ambulances needed during the
      prehospital response in trauma-related multiple casualty events has been
      proposed. Prospective studies of this model are needed to examine its validity
      and applicability.

PMID- 22985619
TI  - Potential of chicken by-products as sources of useful biological resources.
AB  - By-products from different animal sources are currently being utilised for
      beneficial purposes. Chicken processing plants all over the world generate large
      amount of solid by-products in form of heads, legs, bones, viscera and feather.
      These wastes are often processed into livestock feed, fertilizers and pet foods
      or totally discarded. Inappropriate disposal of these wastes causes environmental
      pollution, diseases and loss of useful biological resources like protein, enzymes
      and lipids. Utilisation methods that make use of these biological components for
      producing value added products rather than the direct use of the actual waste
      material might be another viable option for dealing with these wastes. This line
      of thought has consequently led to researches on these wastes as sources of
      protein hydrolysates, enzymes and polyunsaturated fatty acids. Due to the multi
      applications of protein hydrolysates in various branches of science and industry,
      and the large body of literature reporting the conversion of animal wastes to
      hydrolysates, a large section of this review was devoted to this subject. Thus,
      this review reports the known functional and bioactive properties of hydrolysates
      derived from chicken by-products as well their utilisation as source of peptone
      in microbiological media. Methods of producing these hydrolysates including their
      microbiological safety are discussed. Based on the few references available in
      the literature, the potential of some chicken by-product as sources of proteases
      and polyunsaturated fatty acids are pointed out along with some other future
      applications.

PMID- 22985620
TI  - Pharmacodynamic and pharmacokinetic analysis of apoE4 [L261A, W264A, F265A,
      L268A, V269A], a recombinant apolipoprotein E variant with improved biological
      properties.
AB  - Physiological levels of wild-type (wt) apolipoprotein E (apoE) in plasma mediate
      the clearance of cholesterol-rich atherogenic lipoprotein remnants while higher
      than normal plasma apoE concentrations fail to do so and trigger
      hypertriglyceridemia. This property of wt apoE reduces significantly its
      therapeutic value as a lead biological for the treatment of dyslipidemia.
      Recently, we reported the generation of a recombinant apoE variant, apoE4 [L261A,
      W264A, F265A, L268A, V269A] (apoE4mut1) with improved biological functions.
      Specifically, in apoE-deficient (apoE(-/-)) mice this variant can normalize high
      plasma cholesterol levels without triggering hypertriglyceridemia, even at
      supraphysiological levels of expression. In the present study we performed
      pharmacodynamic and pharmacokinetic analysis of apoE4mut1 in experimental mice.
      Using adenovirus-mediated gene transfer in LDL receptor deficient (LDLr(-/-))
      mice, we show that the cholesterol lowering potential of apoE4mut1 is dependent
      on the expression of a functional classical LDLr. Bolus infusion of apoE4mut1
      containing proteoliposomes in apoE(-/-) mice fed western-type diet for 6 weeks
      indicated that exogenously synthesized apoE4mut1 maintains intact its ability to
      normalize the high cholesterol levels of these mice with a maximum
      pharmacological effect obtained at 10h post-treatment. Interestingly, plasma
      cholesterol levels remained significantly reduced up to 24h following intravenous
      administration of apoE4mut1 proteoliposomes. Measurements of plasma apoE levels
      indicated that apoE4mut1 in the form of proteoliposomes used in the study has a
      half-life of 15.8h. Our data suggest that purified apoE4mut1 may be an attractive
      new candidate for the acute correction of hypercholesterolemia in subjects
      expressing functional LDL receptor.

PMID- 22985622
TI  - Some clarifications on the Middle-Upper Paleolithic transition in Abric Romani:
      reply to Camps and Higham (2012).

PMID- 22985623
TI  - Challenge to long term care for the elderly: cold weather impacts institutional
      population more than community-dwelling population.
AB  - OBJECTIVES: To examine whether cold weather affects the institutional population
      more than the community-dwelling population in terms of morbidity requiring
      hospital admission. METHODS: Residence-based hospital discharge data were used to
      compile excess winter hospitalization (EWH) index for the older population (aged
      65 years and above) living in institutions (residential care home for the elderly
      [RCHE] population) and the community-dwelling elderly population in Hong Kong. To
      separate the influence of influenza on the cold-related hospital admissions,
      episodes because of influenza were excluded from this study. RESULTS: In 2009,
      the EWH index for the RCHE population was 22.93% (95% CI: 20.80%-25.09%), which
      was much higher than that for the community-dwelling population (14.09%, 95% CI:
      13.11%-15.08%). The EWH index was higher among RCHE population compared with
      community-dwelling population across different age groups and sex (paired t-test
      one-tailed P= .014). CONCLUSION: The institutional elderly population was more
      vulnerable to the risk of excess hospitalization in winter. There may be room for
      improvement in the living environment of institutions, in particular the ambient
      temperature and personal care, to reduce hospital admissions. Given the expanding
      institutional population, the limited hospital beds, and long waiting queue for
      accident and emergency services, prevention of cold-related hospitalization would
      help to reduce the medical care burden.

PMID- 22985626
TI  - Multivariate statistical analysis for fluoride occurrence in groundwater in the
      Northern region of Ghana.
AB  - The presence of excess fluoride in groundwater in the Northern region of Ghana
      has resulted in the closure of many boreholes for drinking water supply to avoid
      the incidence of fluorosis and other related health effects. The fluoride
      concentration in 357 groundwater samples from the area ranged between 0.0 and
      11.6mg/L, with a mean value of 1.13mg/L. Piper graphical classification,
      correlation coefficients, principal component analysis (PCA) and thermodynamic
      calculations were used as an approach to gain insight into the groundwater
      chemical composition and to help understand the dominant mechanisms influencing
      the occurrence of high fluoride waters. Spatial join procedure was used to
      examine the relationship between the underlying geology of the study area and
      fluoride distribution. Six groundwater types were identified for the area: Ca-Mg
      HCO(3), Ca-Mg-SO(4), Na-Cl, Na-SO(4), Na-HCO(3) and mixed water type. PCA
      performed on the groundwater chemical data resulted in 4 principal components
      (PCs) explaining 72% of the data variance. The PCs represented the predominant
      processes controlling the groundwater chemistry in the study area which include;
      mineral dissolution reactions, ion exchange processes and evapotranspiration
      processes. PHREEQC calculations for saturation indices for the groundwater
      samples indicated they were largely saturated with respect to calcite and under
      saturated with respect to fluorite, suggesting that dissolution of fluorite may
      be occurring in the areas where it is present. A review of the PCA results and an
      evaluation of the equilibrium state of the groundwater based on the saturation
      indices, suggest that some of the processes controlling the overall groundwater
      chemistry in the study area also influenced the fluoride enrichment. These
      predominant processes include the dissolution of the mineral fluorite, anion
      exchange processes (F(-)/OH(-)) involving clay minerals and evapotranspiration
      processes. Elevated fluoride levels in the study area were found to occur
      predominantly in the Saboba and Cheriponi districts and also in the Yendi,
      Nanumba North and South districts. These areas are underlain by the Middle
      Voltain formation (Obossom and Oti beds), comprising mainly of sandstone,
      limestone, conglomerate, shale, arkose and mudstone. Results of the hydrochemical
      analysis show that aside from the boreholes with elevated concentrations of
      fluoride (beyond 1.5mg/L), groundwater in the study area based on the parameters
      analyzed is generally chemically acceptable and suitable for domestic use.

PMID- 22985621
TI  - Apigenin induces DNA damage through the PKCdelta-dependent activation of ATM and
      H2AX causing down-regulation of genes involved in cell cycle control and DNA
      repair.
AB  - Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti
      carcinogenic activities through mechanisms yet not fully defined. In the present
      study, we show that the treatment of leukemia cells with apigenin resulted in the
      induction of DNA damage preceding the activation of the apoptotic program.
      Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta
      (PKCdelta), yet was independent of reactive oxygen species or caspase activity.
      Treatment of monocytic leukemia cells with apigenin induced the phosphorylation
      of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key
      regulators of the DNA damage response, without affecting the ataxia
      telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and
      pharmacological inhibition of PKCdelta abrogated ATM and H2AX phosphorylation,
      whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We
      established that apigenin delayed cell cycle progression at G1/S and increased
      the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that
      apigenin-induced DNA damage led to down-regulation of genes involved in cell
      cycle control and DNA repair. Taken together, the present results show that the
      PKCdelta-dependent activation of ATM and H2AX define the signaling networks
      responsible for the regulation of DNA damage promoting genome-wide mRNA
      alterations that result in cell cycle arrest, hence contributing to the anti
      carcinogenic activities of this flavonoid.

PMID- 22985628
TI  - Efficacy of an antiviral compound to inhibit replication of multiple pestivirus
      species.
AB  - Pestiviruses are economically important pathogens of livestock. An aromatic
      cationic compound (DB772) has previously been shown to inhibit bovine viral
      diarrhea virus (BVDV) type 1 in vitro at concentrations lacking cytotoxic side
      effects. The aim of this study was to determine the scope of antiviral activity
      of DB772 among diverse pestiviruses. Isolates of BVDV 2, border disease virus
      (BDV), HoBi virus, pronghorn virus and Bungowannah virus were tested for in vitro
      susceptibility to DB772 by incubating infected cells in medium containing 0,
      0.006, 0.01, 0.02, 0.05, 0.1, 0.2, 0.39, 0.78, 1.56, 3.125, 6.25, 12.5 or 25MUM
      DB772. The samples were assayed for the presence of virus by virus isolation and
      titration (BDV and BVDV 2) or PCR (HoBi, pronghorn and Bungowannah viruses).
      Cytotoxicity of the compound was assayed for each cell type. Complete inhibition
      of BVDV 2, BDV, and Pronghorn virus was detected when DB772 was included in the
      culture media at concentrations of 0.20MUM and higher. In two of three tests, a
      concentration of 0.05MUM DB772 was sufficient to completely inhibit HoBi virus
      replication. Bungowannah virus was completely inhibited at a concentration of
      0.01MUM DB772. Thus, DB772 effectively inhibits all pestiviruses studied at
      concentrations >0.20MUM. As cytotoxicity is not evident at these concentrations,
      this antiviral compound potentially represents an effective preventative or
      therapeutic for diverse pestiviruses.

PMID- 22985627
TI  - Effects of tailored knowledge enhancement on colorectal cancer screening
      preference across ethnic and language groups.
AB  - OBJECTIVE: Tailoring to psychological constructs (e.g. self-efficacy, readiness)
      motivates behavior change, but whether knowledge tailoring alone changes
      healthcare preferences--a precursor of behavior change in some studies--is
      unknown. We examined this issue in secondary analyses from a randomized
      controlled trial of a tailored colorectal cancer (CRC) screening intervention,
      stratified by ethnicity/language subgroups (Hispanic/Spanish, Hispanic/English,
      non-Hispanic/English). METHODS: Logistic regressions compared effects of a CRC
      screening knowledge-tailored intervention versus a non-tailored control on
      preferences for specific test options (fecal occult blood or colonoscopy), in the
      entire sample (N=1164) and the three ethnicity/language subgroups. RESULTS: Pre
      intervention, preferences for specific tests did not differ significantly between
      study groups (experimental, 64.5%; control 62.6%). Post-intervention, more
      experimental participants (78.6%) than control participants (67.7%) preferred
      specific tests (P<0.001). Adjusting for pre-intervention preferences, more
      experimental group participants than control group participants preferred
      specific tests post-intervention [average marginal effect (AME)=9.5%, 95% CI 5.3
      13.6; P<0.001]. AMEs were similar across ethnicity/language subgroups.
      CONCLUSION: Knowledge tailoring increased preferences for specific CRC screening
      tests across ethnic and language groups. PRACTICE IMPLICATIONS: If the observed
      preference changes are found to translate into behavior changes, then knowledge
      tailoring alone may enhance healthy behaviors.

PMID- 22985629
TI  - Poly(A)-binding protein interacts with the nucleocapsid protein of porcine
      reproductive and respiratory syndrome virus and participates in viral
      replication.
AB  - Interactions between host factors and the viral protein play important roles in
      host adaptation and regulation of virus replication. Poly(A)-binding protein
      (PABP), a host cellular protein that enhances translational efficiency by
      circularizing mRNAs, was identified by yeast two-hybrid screening as a cellular
      partner for PRRSV nucleocapsid (N) protein in porcine alveolar macrophages. The
      specific interaction of PRRSV N protein with PABP was confirmed in infected cells
      by co-immunoprecipitation and in vitro by GST pull-down assay. We showed by
      confocal microscopy that the PABP co-localized with the PRRSV N protein. Using a
      series of deletion mutants, the interactive domain of N protein with PABP was
      mapped to a region of amino acids 52-69. For PABP, C-terminal half, which
      interestingly interacts other translation regulators, was determined to be the
      domain interactive with N protein. Short hairpin RNA (shRNA)-mediated silencing
      of PABP in cells resulted in significantly reduced PRRSV RNA synthesis, viral
      encoded protein expression and viral titer. Overall, the results presented here
      point toward an important role for PABP in regulating PRRSV replication.

PMID- 22985630
TI  - Resveratrol inhibits Epstein Barr Virus lytic cycle in Burkitt's lymphoma cells
      by affecting multiple molecular targets.
AB  - Resveratrol (RV), a polyphenolic natural product present in many plants and
      fruits, exhibits anti-inflammatory, cardio-protective and anti-proliferative
      properties. Moreover, RV affects a wide variety of viruses including members of
      the Herpesviridae family, retroviruses, influenza A virus and polyomavirus by
      altering cellular pathways that affect viral replication itself. Epstein Barr
      Virus (EBV), the causative agent of infectious mononucleosis, is associated with
      different proliferative diseases in which it establishes a latent and/or a lytic
      infection. In this study, we examined the antiviral activity of RV against the
      EBV replicative cycle and investigated the molecular targets possibly involved.
      In a cellular context that allows in vitro EBV activation and lytic cycle
      progression through mechanisms closely resembling those that in vivo initiate and
      enable productive infection, we found that RV inhibited EBV lytic genes
      expression and the production of viral particles in a dose-dependent manner. We
      demonstrated that RV inhibited protein synthesis, decreased reactive oxygen
      species (ROS) levels, and suppressed the EBV-induced activation of the redox
      sensitive transcription factors NF-kB and AP-1. Further insights into the
      signaling pathways and molecular targets modulated by RV may provide the basis
      for exploiting the antiviral activity of this natural product on EBV replication.

PMID- 22985631
TI  - Interference with ERK and STAT signaling pathways and inhibition of hepatitis C
      virus replication by ribavirin.
AB  - Ribavirin in combination with interferon (IFN)-alpha is the approved treatment
      for hepatitis C virus (HCV) infection. Interference of ribavirin with signaling
      events is involved in its biological activities. However, little is known of
      signaling pathways induced by ribavirin following HCV infection. In human
      hepatoma cells, effects of ribavirin on ERK and signal transducers and activators
      of transcription (STAT) pathways, HCV replication, and antiviral gene expression
      were evaluated before and after cell culture-derived HCV infection. Ribavirin
      reduced phosphorylation of Raf, MEK, ERK, Tyk2, and STAT1, but selectively
      increased STAT3 phosphorylation. IFN-alpha synergistically regulated ERK and
      STAT3 phosphorylation with ribavirin, and up-regulated expression and
      phosphorylation of STAT1. Ribavirin dose-dependently decreased HCV RNA
      replication and HCV protein expression, with slight induction of IFN regulatory
      factor 9 and IFN-stimulated gene 15. Ribavirin and IFN-alpha exerted a synergetic
      inhibitory effect on HCV. ERK and STAT pathways were down-regulated by ribavirin
      following HCV infection. These results suggest that ribavirin may mediate anti
      HCV activity through interference with ERK and STAT pathways.

PMID- 22985632
TI  - Natural killer cells: frequency, phenotype and function in healthy cats.
AB  - Natural killer (NK) cells play a central role in innate immunity and have been
      shown to influence adaptive immune responses as well. This study aimed to provide
      a general NK cell quantification and phenotyping in several compartments of
      healthy cats and assess their functional properties. The results indicated that
      NK numbers, both absolute and relative, and phenotype mostly correspond with
      those found in bovine, ovine, human and murine immunology. However, there were
      also distinct differences, especially with regard to the expression of the
      integrin CD11b and the selectin CD62L (between 10 and 30% of feline NK cells
      stain positive for these markers) and the relative frequencies in lymph nodes
      (6.7%), which stand central in NK cell development. Caution should be taken when
      extrapolating findings on NK cell properties over species, notwithstanding the
      generally accepted evolutionary conservation of NK cells and their subtypes. It
      was also shown that K562 cells, the 'golden' target cell line for NK
      functionality tests did not work for feline cells. The feline kidney cell line
      CRFK proved to be very responsive to NK- and NKT-mediated lysis and therefore,
      represents an ideal alternative target. This study is a good reference for NK
      cell numbers, both absolute and relative, phenotype and function in several
      anatomical compartments of healthy cats and for cat-specific cytotoxic assays
      involving both NK and NKT cells.

PMID- 22985633
TI  - A mixture of phytosterols from Dunaliella tertiolecta affects proliferation of
      peripheral blood mononuclear cells and cytokine production in sheep.
AB  - The aim of this study was to investigate the immunomodulatory and anti
      inflammatory role of a mixture of phytosterols extracted from the microalga
      Dunaliella tertiolecta on peripheral blood mononuclear cells (PBMC) isolated from
      sheep. PBMC were treated to determine cell proliferation and cytokine production
      with different sterols: ergosterol (E), a mixture of eleven Algae sterols
      extracted and purified from D. tertiolecta (Algae Extract, AE), a mixture of
      ergosterol and 7-dehydroporiferasterol extracted and purified from D. tertiolecta
      (Purified Extract, PE). Cytokine production (TNF-alpha, IL-6, IL-1beta, and IL
      10) was evaluated after cell treatment with Concanavalin A (Con A) and
      lipopolysaccharide (LPS). The mixture of ergosterol and 7-dehydroporiferasterol
      extracted and purified from D. tertiolecta showed a suppressive effect on cell
      proliferation, and a reduction of pro-inflammatory cytokines production.
      Furthermore, a stimulatory effect on the production of the regulatory cytokine IL
      10 was found. The immunosuppressive effect exerted by the mixture of ergosterol
      and 7-dehydroporiferasterol from D. tertiolecta was dose-dependent both in
      suppressing cell proliferation and in stimulating IL-10 production. Present
      results showed that the immunomodulatory and anti-inflammatory activities were
      more apparent in the purified extract characterized by the mixture of ergosterol
      and 7-dehydroporiferasterol, and might depend on the existence of a synergic
      effect of the structures of the two phytosterols. Furthermore, findings from our
      study suggest that the purified extract characterized by the mixture of
      ergosterol and 7-dehydroporiferasterol from D. tertiolecta could be used to
      reduce immune reactions resulting from inflammatory diseases in sheep production
      systems, and could have innovative implications on the modulation of sheep immune
      system when used as feed supplements.

PMID- 22985634
TI  - Potential evidence for biotype-specific chemokine profile following BVDV
      infection of bovine macrophages.
AB  - Chemokines play a key role in initiating the innate and subsequently adaptive
      immune response by recruiting immune cells to the site of an infection.
      Monocytes/macrophages (MO) are part of the first line of defence against invading
      pathogens, and have been shown to release a variety of chemokines in response to
      infection. Here, we reveal the early transcriptional response of MO to infection
      with cytopathogenic (cp) and non-cytopathogenic (ncp) bovine viral diarrhoea
      strains (BVDV). We demonstrate up-regulation of several key chemokines of the CCL
      and CXCL families in MO exposed to cpBVDV, but not ncpBVDV. In contrast,
      infection of MO with ncpBVDV led to down-regulation of chemokine mRNA expression
      compared to uninfected cells. Data suggest that ncpBVDV can shut down production
      of several key chemokines that play crucial roles in the immune response to
      infection. This study helps to further our understanding of the pathogenesis of
      BVDV infection, highlighting biotype-specific cellular responses.

PMID- 22985635
TI  - Cerebrovascular protection of beta-asarone in Alzheimer's disease rats: a
      behavioral, cerebral blood flow, biochemical and genic study.
AB  - AIM OF THE STUDY: Recent studies have suggested that beta-asarone have
      neuroprotective and cardiovascular protective effects in animal model. However,
      the influence of beta-asarone on cerebrovascular system has not been explored so
      far. Therefore, present study was designed to determine whether repeated
      exposures to beta-asarone resulted in positive effects on cerebrovascular
      function in AD rats. MATERIALS AND METHODS: Alzheimer's disease induced rats was
      established by injecting both D-galactose (D-gal) and aluminum chloride (AlCl(3))
      into abdominal cavity for 42 days. After injection of AlCl(3) and D-gal or saline
      for 28 days, the rats were treated with volume-matched vehicle or beta-asarone
      (25mg/kg, 50mg/kg or 100mg/kg, i.h.) or Nimodipine (40mg/kg, i.g) once daily for
      consecutive 14 days, respectively. Behavioral responses of animals were assessed
      in a Morris water maze. CBF was measured by laser Doppler flowmetry. At the end
      of this period all rats were sacrificed, lactic acid, pyruvic acid content,
      Na+K+ATPase activity were determined in brain tissue homogenate to estimate the
      brain biochemical changes and mRNA expression of ET-1, eNOS and APP was measured
      with real-time RT-PCR method. RESULTS: The spatial navigation task latencies, the
      times through platform zone and the time for the first through platform zone in
      the target quadrant in probe task, rCBF of right parietal lobe, the contents of
      lactic acid, pyruvic acid, and the activity of Na-K-ATP of cortex, and ET-1 and
      eNOS mRNA expression in hippocampus of AG rats were different from those of BG,
      P<0.05; The level of APP mRNA expression in model control group rats was higher
      than that in BG, though there was not a statistically significant difference,
      P>0.05; Compared with AG, HG rats spatial navigation task latencies were shorter,
      in probe task the times through platform zone in the target quadrant were bigger,
      rCBF and blood cell concentration of right parietal lobe were higher, the
      contents of pyruvic acid was lower, the activity of Na-K-ATP was higher, and ET-1
      mRNA expression in hippocampus was lower, P<0.05; The level of eNOS and APP mRNA
      expression in HG rats was lower than that in AG, though there was not a
      statistically significant difference, P>0.05; CONCLUSION: The present results
      suggested that beta-asarone may be useful in memory impairment due to its
      cerebrovascular protection in AD rats and may develop as a therapeutic drug for
      treatment of AD patients.

PMID- 22985636
TI  - JR6, a new compound isolated from Justicia procumbens, induces apoptosis in human
      bladder cancer EJ cells through caspase-dependent pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Numerous efforts have been conducted in searching
      for effective agents against cancer, in particular from herbal medicines.
      Justicia procumbens is a traditional herbal remedy which was produced in the
      south-western and southern provinces of China and Taiwan province used to treat
      fever, pain, and cancer. Here, we identified a new compound 6'-hydroxy justicidin
      A (JR6) from Justicia procumbens, which showed obvious anti-cancer effects.
      MATERIALS AND METHODS: The cytotoxicity activity was assayed using MTT and SRB.
      Intracellular ROS visualization and quantification were acquired by using a laser
      scanning confocal microscopy. Apoptosis was measured using a propidium iodide
      (PI) apoptosis detection kit by flow cytometry. Activation of caspases (caspase
      3, caspase-8, and caspase-9) was evaluated respectively using GloMax luminescence
      detector and Caspase-Glo 3,8,9 assay kits. Loss of mitochondrial membrane
      potential was observed by microscopy using JC-1 dye. Quantitative real-time PCR
      analysis was employed to detect the expression of protein associated with cell
      death. RESULTS: JR6 remarkably inhibited growth in human bladder cancer EJ cells
      by decreasing cell proliferation, reduced the SOD activity, increased the content
      of reactive oxygen species (ROS), and induced apoptosis. Activation of caspase-8,
      caspase-9, and the subsequent activation of caspase-3 indicated that JR6 may be
      inducing intrinsic and extrinsic apoptosis pathways. Caspase-3, caspase-8, and
      caspase-9 inhibition rendered this extract ineffective, thus JR6-induced
      apoptosis is caspase-dependent. JR6 also disrupted the mitochondrial membrane
      potential (Deltapsim) and unregulated the Bax and p53 expressions in EJ cells.
      CONCLUSION: These observations suggest that JR6 induce apoptosis through caspase
      dependent pathway in human bladder cancer EJ cells, emphasizing the importance of
      this traditional medicine and thus presents a potential novel alternative to
      bladder cancer therapy.

PMID- 22985637
TI  - Nonossifying fibroma developed in metaphysis and epiphysis--a case report.
AB  - Nonossifying fibroma is developed in childhood and adolescence and is usually
      asymptomatic. It is typically arises in the metaphysis of long bone and migrates
      toward the diaphysis with growth. We present a very rare case of nonossifying
      fibroma involving metaphysis and epiphysis of the distal femur in a 20-year-old
      man. Nonossifying fibroma is a benign fibroblastic lesion, which is also termed
      benign cortical defect and fibroxanthoma. A nonossifying fibroma rarely causes
      problems and does not interfere with healing or growth. The lesions are usually
      asymptomatic. With growth and remodeling of the bone, the lesion typically
      disappears and is replaced with normal bone. However, the lesion may weaken the
      involved bone, causing fracture. The lesion typically arises in the metaphysis of
      long bones and may migrate toward the diaphysis with growth. There have never
      been reports of nonossifying fibroma involving epiphysis that we know of. We
      report a very rare case of nonossifying fibroma involving metaphysis and
      epiphysis in a young adult. Written, informed consent was obtained from the
      patient to publish this case report, including the images.

PMID- 22985638
TI  - Adverse events of upper GI endoscopy.

PMID- 22985639
TI  - Core curriculum for EMR and ablative techniques.

PMID- 22985640
TI  - Joseph Barnett Kirsner, MD, PhD.

PMID- 22985641
TI  - Comparing apples with apples and oranges: the role of radiofrequency ablation
      alone versus radiofrequency ablation plus EMR for endoscopic management of
      Barrett's esophagus with advanced neoplasia.

PMID- 22985643
TI  - Endoluminal bariatric therapy: beyond weight loss.

PMID- 22985642
TI  - Practice patterns of surveillance endoscopy in a Veterans Affairs database of
      29,504 patients with Barrett's esophagus.
AB  - BACKGROUND: Practice guidelines recommend surveillance endoscopy every 2 to 3
      years among patients with Barrett's esophagus (BE) to detect early neoplastic
      lesions. Although surveys report that >95% of gastroenterologists recommend or
      practice BE surveillance, the extent and patterns of surveillance in clinical
      practice are unknown. OBJECTIVE: To identify the extent and determinants of
      endoscopic surveillance among BE patients. DESIGN: Retrospective cohort study.
      SETTING: A total of 121 Veterans Affairs facilities nationwide. PATIENTS: Veteran
      patients with BE diagnosed from 2003 to 2009, with follow-up through September
      30, 2010. INTERVENTION: Not an interventional study. MAIN OUTCOME MEASUREMENTS:
      The proportions of patients with BE who received any EGD after the index BE EGD
      date. In the subgroup of patients with at least 6 years of follow-up, we also
      calculated proportions for regular (EGD during both 3-year intervals), irregular
      (EGD in only 1 interval), and no surveillance. We examined differences in
      demographics and clinical and facility factors among these groups in unadjusted
      and adjusted analyses. RESULTS: We identified 29,504 patients with BE; 97% were
      men, 83% white, and their mean age was 61.8 years. During a 3.8-year median
      follow-up period, 45.4% of patients with BE received at least one EGD. Among the
      subgroup of 4499 patients with BE who had at least 6 years of follow-up, 23.0%
      had regular surveillance, and 26.7% had irregular surveillance. There was
      considerable facility-level variation in percentages with surveillance EGD across
      the 112 facilities and by geographic region of these facilities. Demographic and
      clinical factors did not explain these variations. Patients with at least one EGD
      were significantly more likely to be white; to be aged <65 years, with a low
      level of comorbidity; to have GERD, obesity, dysphagia, or esophageal strictures;
      to have more outpatient visits; and to be seen in smaller hospitals (<87 beds)
      than those without any EGD. LIMITATIONS: There might be misclassification of BE
      and surveillance EGD. Lack of pathology data on dysplasia, which dictates
      surveillance intervals. CONCLUSION: Endoscopic surveillance for BE is
      considerably less commonly practiced in Veterans Affairs facilities than is self
      reported by physicians. Although several clinical factors are associated with
      variations in surveillance, facility-level factors play a large role. The
      comparative effectiveness of the different practice-based surveillance patterns
      needs to be examined.

PMID- 22985644
TI  - Colonic tattooing: the revival of a black art?

PMID- 22985645
TI  - Translational research in gastroenterology.

PMID- 22985646
TI  - Transcatheter endoscopy for pancreaticobiliary duct diseases (with videos).

PMID- 22985647
TI  - Use of the "bear claw" (over-the-scope-clip) to achieve hemostasis of a large
      gastric ulcer with bleeding visible vessel.

PMID- 22985648
TI  - "Pseudo-target sign" after endoscopic mucosal resection in the upper GI tract.

PMID- 22985651
TI  - Treatment and prevention of wire shearing during EUS-guided biliary drainage.

PMID- 22985649
TI  - Guidewire cannulation: friend or foe.

PMID- 22985653
TI  - Every polyp counts: getting the most out of colonoscopy.

PMID- 22985654
TI  - Closure of pancreatic fistula by gelfoam injection.

PMID- 22985655
TI  - Management of severe sphincterotomy bleeding with recombinant activated factor
      VII.

PMID- 22985657
TI  - Tachy-brady arrhythmias: the critical role of adenosine-induced sinoatrial
      conduction block in post-tachycardia pauses.
AB  - BACKGROUND: In patients with sinoatrial nodal (SAN) dysfunction, atrial pauses
      lasting several seconds may follow rapid atrial pacing or paroxysmal tachycardia
      (tachy-brady arrhythmias). Clinical studies suggest that adenosine may play an
      important role in SAN dysfunction, but the mechanism remains unclear. OBJECTIVE:
      To define the mechanism of SAN dysfunction induced by the combination of
      adenosine and tachycardia. METHODS: We studied the mechanism of SAN dysfunction
      produced by a combination of adenosine and rapid atrial pacing in isolated
      coronary-perfused canine atrial preparations by using high-resolution optical
      mapping (n = 9). Sinus cycle length and sinoatrial conduction time (SACT) were
      measured during adenosine (1-100 MUM) and DPCPX (1 MUM; A1 receptor antagonist; n
      = 7) perfusion. Sinoatrial node recovery time was measured after 1 minute of
      "slow" pacing (3.3 Hz) or tachypacing (7-9 Hz). RESULTS: Adenosine significantly
      increased sinus cycle length (477 +/- 62 ms vs 778 +/- 114 ms; P<.01) and SACT
      during sinus rhythm (41 +/- 11 ms vs 86 +/- 16 ms; P<.01) in a dose-dependent
      manner. Adenosine dramatically affected SACT of the first SAN beat after
      tachypacing (41 +/- 5 ms vs 221 +/- 98 ms; P<.01). Moreover, at high
      concentrations of adenosine (10-100 MUM), termination of tachypacing or atrial
      flutter/fibrillation produced atrial pauses of 4.2 +/- 3.4 seconds (n = 5) owing
      to conduction block between the SAN and the atria, despite a stable SAN intrinsic
      rate. Conduction block was preferentially related to depressed excitability in
      SAN conduction pathways. Adenosine-induced changes were reversible on washout or
      DPCPX treatment. CONCLUSIONS: These data directly demonstrate that adenosine
      contributes to post-tachycardia atrial pauses through SAN exit block rather than
      slowed pacemaker automaticity. Thus, these data suggest an important modulatory
      role of adenosine in tachy-brady syndrome.

PMID- 22985658
TI  - Low doses of ranolazine and dronedarone in combination exert potent protection
      against atrial fibrillation and vulnerability to ventricular arrhythmias during
      acute myocardial ischemia.
AB  - BACKGROUND: Coronary artery disease carries dual risk for atrial tachyarrhythmias
      and sudden cardiac death. OBJECTIVE: To examine whether low-dose ranolazine
      and/or dronedarone can protect against vulnerability to atrial fibrillation (AF)
      and ventricular tachyarrhythmias. METHODS: In chloralose-anesthetized, open-chest
      Yorkshire pigs (n = 15), the proximal segment of left circumflex (LCx) coronary
      artery was occluded to reduce flow by 75%. An electrode catheter was positioned
      on the left atrial appendage to measure AF threshold (AFT) before and during LCx
      coronary artery stenosis before and at 1 hour after dronedarone (0.5 mg/kg
      intravenous bolus over 5 minutes) and/or ranolazine administration (0.6 mg/kg
      intravenous bolus followed by 0.035 mg/kg/min). RESULTS: Before drug
      administration, LCx coronary artery stenosis lowered AFT from 25.2 +/- 1.7 mA
      control (mean +/- SEM) to 4.9 +/- 1.0 mA baseline (P<.01). At the low doses,
      neither ranolazine (plasma concentration 2.4 +/- 0.6 MUM) nor dronedarone (plasma
      concentration 20.9 +/- 3.5 nM) alone blunted the ischemia-induced reduction in
      AFT but were effective together (from 25.2 +/- 1.7 mA control to 22.0 +/- 3.0 mA
      during stenosis; P = not significant). AF duration (P<.03) and AF inducibility (P
      = .012) were reduced by ranolazine and dronedarone together but not by either
      drug alone. Concurrently, combined but not separate administration blunted the
      ischemia-induced surge in T-wave heterogeneity, a marker of risk for ventricular
      tachyarrhythmias (from 43.1 +/- 11.1 MUV control to 149.7 +/- 15.1 MUV during
      stenosis, P<.001, compared to 61.7 +/- 13.7 MUV control to 83.7 +/- 15.8 MUV
      during stenosis, P = not significant). CONCLUSIONS: Combined administration of
      low doses of ranolazine and dronedarone exerts a potent antiarrhythmic action on
      ischemia-induced vulnerability to AF and ventricular tachyarrhythmias due to
      direct effects on myocardial electrical properties.

PMID- 22985659
TI  - To the Editor--Sympathetic innervation of the anterior left ventricular wall by
      the right and left stellate ganglia.

PMID- 22985660
TI  - Another piece of the puzzle, but still no answer.

PMID- 22985661
TI  - Ventricular repolarization gradient and electrocardiogram characteristics of Tako
      Tsubo cardiomyopathy.

PMID- 22985662
TI  - Regional citrate anticoagulation in patients with liver failure--time for a
      rethink?
AB  - Regional citrate anticoagulation (RCA) for continuous renal replacement therapy
      (CRRT) has become increasingly attractive in recent years due to its favourable
      low bleeding risk profile. Its use in liver failure, however, has been limited
      due to the risk of citrate accumulation and toxicity. In the previous issue of
      Critical Care, Schultheiss and colleagues look at CRRT using RCA in liver failure
      patients. They demonstrate that citrate accumulation can be predicted using the
      total calcium (Ca(tot)) to ionised calcium (Ca(ion)) ratio (Catot/Ca(ion)), and
      determine that despite the occurrence of significant citrate accumulation, the
      effects of citrate accumulation are not as severe as might have been expected.
      This study raises interesting prospects with regard to RCA use in liver failure,
      and we postulate that citrate may have a role as a prognostic marker of metabolic
      capacity much as in the way of lactate and methacetin. However, further studies
      are warranted, in particular examining its application in subgroups of liver
      failure (chronic, acute, hyperacute and subacute), before its use becomes
      commonplace.

PMID- 22985663
TI  - [Intensive insulin therapy in type 2 diabetes mellitus].
AB  - In the last couple of years, the intensive conservative insulin treatment (basal
      bolus regime) became more and more popular even in patients with type 2 diabetes.
      Using this insulin treatment, continuous patient education, co-operation between
      the medical team (diabetologist, dietician and diabetes-nurses) and the patient
      as well as the availability of modern insulins, pens and glucometers are of great
      importance. Clearly, the basal-bolus treatment with human insulin has advantages
      over the conservative (conventional) treatment with twice daily premix insulins.
      Moreover, the basal-bolus treatment with insulin-analogues proved to be superior
      in some aspects as compared to human insulins. The intensive insulin treatment
      (basal-bolus regime with insulin-analogues) approaches the optimal insulin
      substitution and, with its use the adequate correction of each element of the
      glucose triad (fasting blood glucose, postprandial blood glucose, HbA1c) should
      be considered feasible even in patients with type 2 diabetes.

PMID- 22985664
TI  - [Relevance of long non-coding RNAs in tumour biology].
AB  - The discovery of the biological relevance of non-coding RNA molecules represents
      one of the most significant advances in contemporary molecular biology. It has
      turned out that a major fraction of the non-coding part of the genome is
      transcribed. Beside small RNAs (including microRNAs) more and more data are
      disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length
      that are implicated in the regulation of several basic molecular processes (cell
      proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of
      these long non-coding RNAs have been associated with human tumours, including
      H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in
      various neoplasms relative to healthy tissues. Long non-coding RNAs may represent
      novel markers of molecular diagnostics and they might even turn out to be targets
      of therapeutic intervention.

PMID- 22985665
TI  - [Necrotizing autoimmune myopathy].
AB  - Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized
      by symmetrical proximal muscle weakness. One of them is the subgroup of
      necrotizing autoimmune myopathy, which has recently been recognized as a separate
      entity. In addition to the typical symmetrical muscle weakness, it is
      characterized by very high creatine kinase levels, myopathic triad in the
      electromyography, and myocyte necrosis without significant inflammation. The
      paper aims to review this rare entity, which has to be diagnosed and treated
      quickly in every case.

PMID- 22985666
TI  - [Specific quality of life factors in patients with inflammatory bowel disease].
AB  - INTRODUCTION: Inflammatory bowel disease is a chronic disease with a fluctuating
      course and unknown origin. Its two major forms are Crohn's disease and ulcerative
      colitis. OBJECTIVE: The authors attempted to analyse the quality of life of
      patients with inflammatory bowel disease as compared to healthy persons and
      patients with asthma in order to identify specific factors which most
      significantly affect the quality of life of these patients. METHOD: 269 subjects
      participated in the study (control group, 115 subjects; Crohn's disease, 67
      patients; ulcerative colitis, 25 patients; asthma, 62 patients). The following
      methods were used: WHO-5, IIRS, SIBDQ and AQLQ(S) questionnaires and content
      analysis. RESULTS: Patients with inflammatory bowel disease had the worst quality
      of life with respect to both subjective well-being and burden of disease. The
      results obtained from questionnaires developed for the analysis of quality of
      life indicated that extraintestinal symptoms and emotional problems are the major
      factors which interfere with the quality of life of patients with inflammatory
      bowel disease. These findings were confirmed by content analysis of interviews
      with patients. CONCLUSIONS: The authors recommend that more attention should be
      paid to improving the quality of life of patients with inflammatory bowel disease
      and helping them to live with the illness, especially at the level of
      interpersonal relations.

PMID- 22985667
TI  - [The Bible--a medical approach VII].

PMID- 22985669
TI  - 2-BFI ameliorates EAE-induced mouse spinal cord damage: effective therapeutic
      time window and possible mechanisms.
AB  - Our previous studies showed that ligands to type 2 imidazoline receptors (I2R),
      including 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) and Idazoxan, were effective
      in reducing spinal cord inflammation caused by experimental autoimmune
      encephalomyelitis (EAE). In the present study, we determined the effective
      therapeutic time window of 2-BFI and found that administration of 2-BFI in mice
      before the appearance of ascending flaccid paralysis (1-10 days post
      immunization), but not during the period when neurological deficits occurred (11
      20 days post immunization), significantly ameliorated EAE-induced neurobehavioral
      deficits, reduced the infiltration of inflammatory cells into the spinal cord,
      and reduced the level of demyelination. More interestingly, giving 2-BFI during 1
      10 days post immunization selectively suppressed IL-17 levels in the peripheral
      blood, which strongly suggests that IL-17 may be a good early marker to indicate
      EAE progression and that 2-BFI may target CD4+ T lymphocytes, especially Th17
      cells to reduce IL-17 expression. Collectively, these studies led us to envisage
      that 2-BFI can be a useful drug to treat multiple sclerosis (MS) when used in
      combination with an early indicator of MS progression, such as IL-17.

PMID- 22985670
TI  - A neurocognitive perspective on rhyme awareness: the N450 rhyme effect.
AB  - Rhyme processing is reflected in the electrophysiological signals of the brain as
      a negative deflection for non-rhyming as compared to rhyming stimuli around 450
      ms after stimulus onset. Studies have shown that this N450 component is not
      solely sensitive to rhyme but also responds to other types of phonological
      overlap. In the present study, we examined whether the N450 component can be used
      to gain insight into the global similarity effect, indicating that rhyme judgment
      skills decrease when participants are presented with word pairs that share a
      phonological overlap but do not rhyme (e.g., bell-ball). We presented 20 adults
      with auditory rhyming, globally similar overlapping and unrelated word pairs. In
      addition to measuring behavioral responses by means of a yes/no button press, we
      also took EEG measures. The behavioral data showed a clear global similarity
      effect; participants judged overlapping pairs more slowly than unrelated pairs.
      However, the neural outcomes did not provide evidence that the N450 effect
      responds differentially to globally similar and unrelated word pairs, suggesting
      that globally similar and dissimilar non-rhyming pairs are processed in a similar
      fashion at the stage of early lexical access.

PMID- 22985671
TI  - Exogenous GDNF increases the migration of the neural stem cells with no
      protection against kainic acid-induced excitotoxic cell death in rats.
AB  - Glia cell line-derived neurotrophic factor (GDNF) is a potent survival factor for
      several neuron types. In this study, we have evaluated the utility of adenovirus
      based vectors (Ad) and hippocampal neural stem cells (NSCs) as genetic tools for
      the delivery of a therapeutic protein, GDNF, in hippocampus tissues damaged by
      kainic acid (KA)-induced excitotoxicity. The experimental animals were treated
      with KA 3 days prior to exposure to Ad-GDNF, NSCs, and NSCs infected with Ad-GDNF
      (Ad-GDNF-NSCs). Seven days after the treatments with Ad-GDNF, NSCs and Ad-GDNF
      NSCs, the effects of the treatments were evaluated. GAD-67 labeled cells
      originating from the transplanted NSCs were observed at increased levels in the
      Ad-GDNF-NSCs-treated rats as compared to the NSCs-only rats. In situ apoptosis
      assays showed that the levels of TUNEL-positive cells were slightly, but not
      significantly, reduced in the Ad-GDNF and Ad-GDNF-NSCs groups, as compared to the
      saline and NSCs only groups. GDNF expression by NSCs and Ad-GDNF was upregulated
      as the consequence of adenoviral gene delivery in the NSCs and Ad-GDNF-treated
      rats, and the transplanted NSCs were shown to have migrated to the hippocampal
      regions in Ad-GDNF-NSCs rats to a greater degree than in the NSCs-only rats.
      Furthermore, in the region in which the NSCs were detected, GDNF and GAD-67
      expression were increased. These results indicate that the migration and
      differentiation of NSCs may be associated with the expression of GDNF. However,
      cell death consequent to KA administration was not prevented by upregulated GDNF
      and NSCs transplantation. Collectively, our results indicate that GDNF may exert
      effects on the migration and differentiation of NSCs, but there are no protective
      properties with regard to excitotoxically damaged hippocampal tissue.

PMID- 22985672
TI  - Administration of dehydroepiandrosterone (DHEA) increases serum levels of
      androgens and estrogens but does not enhance short-term memory in post-menopausal
      women.
AB  - The current study examines the effect of administering dehydroepiandrosterone
      (DHEA) on short-term memory. This experiment used a double-blind placebo
      controlled cross-over design to explore the effects of a four week regimen of 50
      mg oral DHEA on performance on the digit span, verbal span, and modified
      Sternberg (Oberauer) tasks. The results demonstrate that the current regimen of
      drug administration significantly increases serum levels of DHEA, DHEAS,
      testosterone and estrone and substantially alters the patterns of correlations
      among the serum levels of these hormones. Despite this substantial change in the
      hormonal milieu, DHEA administration produced no beneficial effects on cognitive
      performance in the digit span, verbal span, or modified Sternberg paradigm tasks.
      Ancillary analyses of the relation between hormone levels and cognitive
      performance demonstrated a strong positive correlation between DHEA levels and
      performance on digit span forward/backward and verbal span forward in the placebo
      drug condition, but not in the DHEA condition. We interpret the juxtaposition of
      the null results of DHEA administration and the correlation of DHEA levels and
      performance in the placebo condition to indicate that the referenced correlations
      arise because a third variable (i.e., age) is associated with both performance
      and DHEA levels. Additional analyses supported this hypothesis.

PMID- 22985673
TI  - Surface engineering for enhancement of sensitivity in an underlap-FET biosensor
      by control of wettability.
AB  - The present work aims to improve the sensitivity of an electrical biosensor by
      simply changing a surface property of the passivation layer, which covers the
      background region except for the sensing site for electrical isolation among
      adjacent interconnection lines. The hydrophobic passivation layer dramatically
      enhances the sensitivity of the biosensor when compared with a hydrophilic
      passivation layer. A revamped metal oxide semiconductor field-effect transistor
      (MOSFET), which has a designed underlap region between a gate and a drain, is
      used as the electrical biosensor. A thin film of CYTOP(TM) and silicon nitride is
      used as the hydrophobic and hydrophilic passivation layers, respectively. The
      surface antigen and its specific antibody of the avian influenza virus were
      employed as the probe and target biomolecule, respectively, to confirm the
      enhanced sensitivity of the proposed biosensor. By using hydrophobic passivation,
      the limit of detection of the biosensor was improved up to 100-fold compared with
      that resulting from hydrophilic passivation. Therefore, a simple surface
      engineering to control surface wettability can notably improve the sensitivity of
      a biosensor without additional efforts, such as modifying the sensor structure,
      optimizing the bio-treatment protocol, or increasing the binding yield between a
      probe and its target, among other efforts.

PMID- 22985674
TI  - Emerging organic contaminants in groundwater in Spain: a review of sources,
      recent occurrence and fate in a European context.
AB  - This paper reviewed the presence of emerging organic contaminants (EOCs) that
      have been found in the groundwater in Spain in both, rural and urban areas. The
      list of compounds included pesticides, pharmaceutical active compounds (PhACs),
      selected industrial compounds, drugs of abuse (DAs), estrogens, personal care
      products and life-style compounds. The main sources of pollution and possible
      pathways have been summarised in this review. EOCs are likely to enter to the
      aquifer mainly through the effluents of waste water treatment plants (WWTPs) and
      are present in groundwater at concentrations of ng/L to MUg/L. The most studied
      compounds in Spanish groundwater were pesticides followed by industrial compounds
      and PhACs. It is important to mention that compared to other water bodies, such
      as rivers, groundwater is considerably less contaminated, which may be indicative
      of the natural attenuation capacity of the aquifers. However, some EOCs have
      sometimes been detected at higher concentration levels in the aquifer than in the
      rivers, indicating the need for further research to understand their behaviour in
      the aquifers. For a wide array of compounds, their maximum concentrations show
      values above the European groundwater quality standard for individual pesticides
      (0.1 MUg/L). Therefore, to preserve groundwater quality against deterioration it
      is necessary to define environmental groundwater thresholds for the non-regulated
      compounds.

PMID- 22985675
TI  - Is there an environmental benefit from remediation of a contaminated site?
      Combined assessments of the risk reduction and life cycle impact of remediation.
AB  - A comparative life cycle assessment is presented for four different management
      options for a trichloroethene-contaminated site with a contaminant source zone
      located in a fractured clay till. The compared options are (i) long-term
      monitoring (ii) in-situ enhanced reductive dechlorination (ERD), (iii) in-situ
      chemical oxidation (ISCO) with permanganate and (iv) long-term monitoring
      combined with treatment by activated carbon at the nearby waterworks. The life
      cycle assessment included evaluation of both primary and secondary environmental
      impacts. The primary impacts are the local human toxic impacts due to contaminant
      leaching into groundwater that is used for drinking water, whereas the secondary
      environmental impacts are related to remediation activities such as monitoring,
      drilling and construction of wells and use of remedial amendments. The primary
      impacts for the compared scenarios were determined by a numerical risk assessment
      and remedial performance model, which predicted the contaminant mass discharge
      over time at a point of compliance in the aquifer and at the waterworks. The
      combined assessment of risk reduction and life cycle impacts showed that all
      management options result in higher environmental impacts than they remediate, in
      terms of person equivalents and assuming equal weighting of all impacts. The ERD
      and long-term monitoring were the scenarios with the lowest secondary life cycle
      impacts and are therefore the preferred alternatives. However, if activated
      carbon treatment at the waterworks is required in the long-term monitoring
      scenario, then it becomes unfavorable because of large secondary impacts. ERD is
      favorable due to its low secondary impacts, but only if leaching of vinyl
      chloride to the groundwater aquifer can be avoided. Remediation with ISCO caused
      the highest secondary impacts and cannot be recommended for the site.

PMID- 22985676
TI  - Extended-release naltrexone plus medical management alcohol treatment in primary
      care: findings at 15 months.
AB  - The feasibility of long-term extended-release naltrexone (XR-NTX) alcohol
      treatment is unknown. Following an initial 12-week, single-arm, observational
      trial of XR-NTX plus medical management (MM) in primary care, we offered 48
      additional weeks of XR-NTX treatment (12 additional monthly injections) in two
      public primary care clinics as a naturalistic extension study. Of 65 alcohol
      dependent adults initiating XR-NTX treatment, 40 (62%) completed the initial 12
      week XR-NTX observational trial, and 19 (29%) continued treatment for a median of
      38 weeks total (range, 16-72 weeks; median 8 total XR-NTX injections). Among
      active extension phase participants, self-reported rates of drinking days (vs.
      last 30 days pre-treatment baseline) were low: median 0.2 vs. 6.0 drinks per day;
      82 vs. 38% days abstinent; 11 vs. 61% heavy drinking days. Long-term XR-NTX
      treatment in a primary care MM model was feasible and may promote lasting
      drinking reductions or alcohol abstinence (clinical trial: NCT00620750).

PMID- 22985677
TI  - Possible barriers to enrollment in substance abuse treatment among a diverse
      sample of Asian Americans and Pacific Islanders: opinions of treatment clients.
AB  - This mixed methods study examined motivations and barriers to substance abuse
      treatment entry and treatment continuation among Asian American and Pacific
      Islander (AAPI) substance users. AAPI substance users (N = 61) were recruited
      from substance abuse treatment programs in California and Hawaii. Semi-structured
      interviews and interviewer-administered surveys assessed barriers and
      facilitators to entering substance abuse treatment. Barriers included peer
      pressure, family influences, and face loss concerns. Facilitators included peer
      support, involvement in the criminal justice system, a perceived need for
      treatment, and culturally competent substance abuse treatment services. Family
      and peer influences may act as both facilitators and impediments. AAPI substance
      using populations face many of the same individual-level and structural and
      systems barriers to entry to treatment as other substance using populations.
      However, similar to other racial/ethnic minority groups, it is important to
      address cultural differences and develop culturally competent substance abuse
      treatments for the AAPI population.

PMID- 22985678
TI  - Middle ear implant in conductive and mixed congenital hearing loss in children.
AB  - PURPOSE: Active middle ear implant can be used in children and adolescents with
      congenital hearing loss. The authors report their experience with the semi
      implantable Medel Vibrant Soundbridge((r)) (VSB) in the audiologic rehabilitation
      of such patients. METHODS: In this retrospective study, audiological and surgical
      data of 10 children (10.5+/-4 years) implanted with 12 VSB in 2 tertiary cares
      ENT Departments were analysed. RESULTS: Two children with bilateral external
      auditory canal (EAC) atresia and mixed hearing loss (mean air conduction (AC)
      thresholds=65dB HL) were bilaterally implanted. Eight children presented with
      microtia associated with EAC atresia bilaterally (n=3) and unilaterally (n=5).
      All of them had a conductive hearing loss in the implanted ear (mean (AC)
      thresholds were 58.75dB HL preoperatively). The Floating Mass Transducer was
      crimped on the long process of the incus (n=8) or on the suprastructure of the
      stapes (n=4). There were no intra- or postoperative surgical complications. All
      the children wore their implants after 5 weeks. Postoperative mean bone
      conduction (BC) thresholds were unchanged. The mean aided thresholds with VSB
      (four frequencies warble tones at 0.5, 1, 2 and 4 kHz) were 28dB HL (+/- 10).
      Word discrimination threshold in quiet conditions in free field with the VSB
      unilaterally activated was 50% at 38dB SPL (+/- 9). CONCLUSION: The results
      indicate that satisfaction of the children and their parents is very encouraging
      but surgeons should be cautious with this new approach in relation to the pinna
      reconstruction and to possible risks to inner ear and facial nerve.

PMID- 22985679
TI  - Engineering plant metabolism into microbes: from systems biology to synthetic
      biology.
AB  - Plant metabolism represents an enormous repository of compounds that are of
      pharmaceutical and biotechnological importance. Engineering plant metabolism into
      microbes will provide sustainable solutions to produce pharmaceutical and fuel
      molecules that could one day replace substantial portions of the current fossil
      fuel based economy. Metabolic engineering entails targeted manipulation of
      biosynthetic pathways to maximize yields of desired products. Recent advances in
      Systems Biology and the emergence of Synthetic Biology have accelerated our
      ability to design, construct and optimize cell factories for metabolic
      engineering applications. Progress in predicting and modeling genome-scale
      metabolic networks, versatile gene assembly platforms and delicate synthetic
      pathway optimization strategies has provided us exciting opportunities to exploit
      the full potential of cell metabolism. In this review, we will discuss how
      systems and synthetic biology tools can be integrated to create tailor-made cell
      factories for efficient production of natural products and fuel molecules in
      microorganisms.

PMID- 22985680
TI  - Mental health needs assessment after the Gulf Coast oil spill-Alabama and
      Mississippi, 2010.
AB  - INTRODUCTION: Previous oil spills and disasters from other human-made events have
      shown that mental health effects to the affected population are widespread and
      can be significant. HYPOTHESIS/PROBLEM: There has been concern regarding the
      likelihood that existing public health surveillance was not capturing the mental
      health effects to the population affected by the Gulf Coast oil spill. The
      objectives of this study were to assess the mental health needs of coastal
      communities in the states of Alabama and Mississippi following the Deepwater
      Horizon oil spill. METHODS: A cluster sampling methodology was used to assess the
      mental health status of coastal residents in three counties in Alabama four
      months following the 2010 Deepwater Horizon oil spill, and in the Gulf Coast
      counties in Mississippi 5.5 months after the oil spill. RESULTS: A total of 469
      residents of the selected areas were interviewed. Between 15.4 and 24.5% of the
      respondents reported depressive symptoms, with 21.4-31.5% reporting symptoms
      consistent with an anxiety disorder, and 16.3-22.8% reporting >=14 mentally
      unhealthy days within the past 30 days. Overall, there were more negative quality
      of life indicators and negative social context outcomes than in the state's
      Behavioral Risk Factor Surveillance System (BRFSS) survey. Between 32.1% and
      35.7% of all households reported decreased income since the oil spill, and 35.5
      38.2% of all households reported having been exposed to oil. CONCLUSION: The
      proportion of respondents reporting negative mental health parameters in the
      affected Alabama and Mississippi coastal communities is higher than the
      proportion reported in the 2008 and 2009 BRFSS state reports, suggesting that the
      public health response to the Deepwater Horizon oil spill should focus on mental
      health services in these communities.

PMID- 22985681
TI  - The phenetic structure of Aedes albopictus.
AB  - The large and recent migrations of the main vector of the Chikungunya virus,
      Aedes albopictus, raise questions about the epidemiological impact of possible
      microevolutionary changes in new territories. Quantitative traits are suitable to
      detect such changes as induced by environmental adaptations, local competition
      and founder effects. Using landmark-based geometric morphometrics, we compared
      the size and shape of 22 populations (1572 females) of Ae. albopictus. The
      collection sites covered five countries around the world, with special emphasis
      on Asia, which is assumed to be the origin of the vector. Some collections came
      from places where an important epidemic outbreak of Chikungunya has recently
      occurred. Quantitative comparisons were based on 18 anatomical landmarks on the
      wing. To contrast geographic and possible interspecific shape variation, close
      species were introduced in the sample, namely five Aedes riversi and nine Ae.
      flavopictus from Japan. The three species had similar size, but they were clearly
      separated by shape. Within Ae. albopictus, there was general agreement on size
      variation with the available climatic data. Shape variation was less related to
      climatic data than to either geography or a known itinerary of past territorial
      expansion. Thus, two main clusters were distinguished by wing shape variation:
      the first one composed of the Southeast Asian sample, the second one grouping
      Japan, Florida, Hawaii and the Reunion Island samples. The Southeast Asian
      countries, assumed to be at the origin of the geographic expansion of the
      mosquito, had similar wings and constituted a distinct group where localities
      clustered into northern and southern localities. Contrasting with this
      homogeneous group, very distant localities such as United States (US) and Japan
      shared a common shape pattern. The US Ae. albopictus samples (Hawaii and Florida)
      were indeed very similar to the Japanese samples, with Florida behaving exactly
      like a northern Japanese locality, close to Tokyo and Yokohama. Shape proximity
      among these distant areas could be explained by a common and relatively recent
      ancestor, as generally suggested in the literature. The three Reunion Island
      samples conformed a group external to the Southeast Asian countries, loosely
      connected to the remaining localities. Thus, areas where recent epidemics took
      place, the Reunion Island and the southernmost localities of Thailand, did not
      cluster together, but represented separate groups. In sum, the size of the wing
      was apparently under the influence of climatic factors, while its shape could
      contribute information on species and geographic differences. Apparent departures
      from expectations based on geography were explained by known past and present
      migratory routes. These patterns of shape variation were compatible with genetic
      drift, suggesting microevolutionary changes probably induced by the expansion of
      the Ae. albopictus mosquito.

PMID- 22985682
TI  - A review of the infection, genetics, and evolution of Neospora caninum: from the
      past to the present.
AB  - This paper is a review of current knowledge on Neospora caninum in the context of
      other apicomplexan parasites and with an emphasis on: life cycle, disease,
      epidemiology, immunity, control and treatment, evolution, genomes, and biological
      databases and web resources. N. caninum is an obligate, intracellular, coccidian,
      protozoan parasite of the phylum Apicomplexa. Infection can cause the clinical
      disease neosporosis, which most notably is associated with abortion in cattle.
      These abortions are a major root cause of economic loss to both the dairy and
      beef industries worldwide. N. caninum has been detected in every country in which
      a study has been specifically conducted to detect this parasite in cattle. The
      major mode of transmission in cattle is transplacental (or vertical) transmission
      and several elements of the N. caninum life cycle are yet to be studied in
      detail. The outcome of an infection is inextricably linked to the precise timing
      of the infection coupled with the status of the immune system of the dam and
      foetus. There is no community consensus as to whether it is the dam's pro
      inflammatory cytotoxic response to tachyzoites that kills the foetus or the
      tachyzoites themselves. From economic analysis the most cost-effective approach
      to control neosporosis is a vaccine. The perfect vaccine would protect against
      both infection and the clinical disease, and this implies a vaccine is needed
      that can induce a non-foetopathic cell mediated immunity response. Researchers
      are beginning to capitalise on the vast potential of -omics data (e.g. genomes,
      transcriptomes, and proteomes) to further our understanding of pathogens but
      especially to identify vaccine and drug targets. The recent publication of a
      genome for N. caninum offers vast opportunities in these areas.

PMID- 22985683
TI  - Phylogeography of foot-and-mouth disease virus serotype O in Ecuador.
AB  - Foot-and-mouth disease virus (FMDV) is the causative agent of the most important
      disease of domestic cattle, foot-and-mouth disease. In Ecuador, FMDV is
      maintained at an endemic state, with sporadic outbreaks. To unravel the tempo and
      mode of FMDV spread within the country we conducted a Bayesian phylogeographic
      analysis using a continuous time Markov chain (CTMC) to model the diffusion of
      FMDV between Ecuadorian provinces. We implement this framework through Markov
      chain Monte Carlo available in the BEAST package to study 90 FMDV serotype O
      isolates from 17 provinces in the period 2002-2010. The Bayesian approach also
      allowed us to test hypotheses on the mechanisms of viral spread by incorporating
      environmental and epidemiological data in our prior distributions and perform
      Bayesian model selection. Our analyses suggest an intense flow of viral strains
      throughout the country that is possibly coupled to animal movements and
      ecological factors, since most of inferred viral spread routes were in Coast and
      Highland regions. Moreover, our results suggest that both short- and long-range
      spread occur within Ecuador. The province of Esmeraldas, in the border with
      Colombia and where most animal commerce is done, was found to be the most
      probable origin of the circulating strains, pointing to a transboundary behavior
      of FMDV in South America. These findings suggest that uncontrolled animal
      movements can create a favorable environment for FMDV maintenance and pose a
      serious threat to control programmes. Also, we show that phylogeographic modeling
      can be a powerful tool in unraveling the spatial dynamics of viruses and
      potentially in controlling the spread of these pathogens.

PMID- 22985684
TI  - Comparative effects on glucose absorption of intragastric and post-pyloric
      nutrient delivery in the critically ill.
AB  - INTRODUCTION: Studies in the critically ill that evaluate intragastric and post
      pyloric delivery of nutrient have yielded conflicting data. A limitation of these
      studies is that the influence in the route of feeding on glucose absorption and
      glycaemia has not been determined. METHODS: In 68 mechanically ventilated
      critically ill patients, liquid nutrient (100 ml; 1 kcal/ml containing 3 g of 3-O
      Methyl-D-glucopyranose (3-OMG), as a marker of glucose absorption), was infused
      into either the stomach (n = 24) or small intestine (n = 44) over six minutes.
      Blood glucose and serum 3-OMG concentrations were measured at regular intervals
      for 240 minutes and the area under the curves (AUCs) calculated for 'early'
      (AUC60) and 'overall' (AUC240) time periods. Data are presented as mean (95%
      confidence intervals). RESULTS: Glucose absorption was initially more rapid
      following post-pyloric, when compared with intragastric, feeding (3-OMG AUC60:
      intragastric 7.3 (4.3, 10.2) vs. post-pyloric 12.5 (10.1, 14.8) mmol/l.min; P =
      0.008); however, 'overall' glucose absorption was similar (AUC240: 49.1 (34.8,
      63.5) vs. 56.6 (48.9, 64.3) mmol/l.min; P = 0.31). Post-pyloric administration of
      nutrients was also associated with greater increases in blood glucose
      concentrations in the 'early' period (AUC60: 472 (425, 519) vs. 534 (501, 569)
      mmol/l.min; P = 0.03), but 'overall' glycaemia was also similar (AUC240: 1,875
      (1,674, 2,075) vs. 1,898 (1,755, 2,041) mmol/l.min; P = 0.85). CONCLUSIONS: In
      the critically ill, glucose absorption was similar whether nutrient was
      administered via a gastric or post-pyloric catheter. These data may have
      implications for the perceived benefit of post-pyloric feeding on nutritional
      outcomes and warrant further investigation.

PMID- 22985685
TI  - Neural activity in the hippocampus during conflict resolution.
AB  - This study examined configural association theory and conflict resolution models
      in relation to hippocampal neural activity during positive patterning tasks.
      According to configural association theory, the hippocampus is important for
      responses to compound stimuli in positive patterning tasks. In contrast,
      according to the conflict resolution model, the hippocampus is important for
      responses to single stimuli in positive patterning tasks. We hypothesized that if
      configural association theory is applicable, and not the conflict resolution
      model, the hippocampal theta power should be increased when compound stimuli are
      presented. If, on the other hand, the conflict resolution model is applicable,
      but not configural association theory, then the hippocampal theta power should be
      increased when single stimuli are presented. If both models are valid and
      applicable in the positive patterning task, we predict that the hippocampal theta
      power should be increased by presentation of both compound and single stimuli
      during the positive patterning task. To examine our hypotheses, we measured
      hippocampal theta power in rats during a positive patterning task. The results
      showed that hippocampal theta power increased during the presentation of a single
      stimulus, but did not increase during the presentation of a compound stimulus.
      This finding suggests that the conflict resolution model is more applicable than
      the configural association theory for describing neural activity during positive
      patterning tasks.

PMID- 22985686
TI  - Dorsolateral periaqueductal gray stimulation prior to retrieval potentiates a
      contextual fear memory in rats.
AB  - The association of a neutral context with an aversive stimulus, such as foot
      shock, result in a contextual fear memory. A growing number of evidence have
      revealed that prior exposure to diverse threatening situations facilitates the
      encoding of fear memory during acquisition and such reports support the
      widespread notion that emotionally arousal results in stronger and long-lasting
      memories. However, few studies have investigated if a threatening experience can
      affect the recall and the persistence of such fear memory trace. To test the
      hypothesis that an emotionally negative experience could modify the retrieval of
      a memory and potentiate the expression of a fear memory, the present study used
      the chemical stimulation (microinjection of NMDA) of the dorsolateral
      periaqueductal gray matter (dlPAG) of rats in order to induce an aversive
      emotional state. Such stimulation was performed one day after a weak fear
      training protocol, and the fear expression was analyzed in subsequent re
      exposures to the conditioned context. The results showed that the negative
      emotional state induced by the dlPAG stimulation enhanced the fear memory trace
      when this trace was reactivated one day after this aversive experience.
      Additionally, the potentiation of the fear response was contingent to the
      associated context since no potentiation was evident when NMDA-stimulated animals
      were subsequently placed in a non-associated context. Finally, the model suggests
      that the enhancement of fear responses is long-lasting since NMDA-treated animals
      performed a robust fear response six days after memory retrieval.

PMID- 22985687
TI  - High levels of wheel running protect against behavioral sensitization to cocaine.
AB  - Although there is no doubt that the direct action of stimulant drugs on the brain
      is necessary for sensitization to their behavioral stimulating effects, several
      experiments indicate that drug action is often not sufficient to produce
      sensitization. There is considerable evidence that many individual
      characteristics and experiential variables can modulate the behavioral and neural
      changes that are seen following repeated exposure to stimulant drugs. In the work
      presented here, we examined whether chronic wheel running would modulate
      behavioral sensitization to cocaine, and whether any such influence was
      contingent on individual differences in wheel running. We found that a 5- or 10
      week experience with wheel running protects against behavioral sensitization to
      cocaine but only in animals with a natural tendency to run the most.
      Understanding the mechanism underlying the modulating effect of wheel running on
      behavioral sensitization may have important implications for future studies on
      the link between drug-induced behavioral and neural adaptations.

PMID- 22985689
TI  - Quantification of growth hormone mRNA in blood.
AB  - BACKGROUND: Growth hormone (GH) is present in human lymphocytes and the relative
      concentration of GH mRNA in circulating cells is reportedly increased in patients
      with acromegaly. No quantitative assay has been described to measure GH in
      circulating cells. METHODS: To measure GH mRNA, we used real-time reverse
      transcriptase (RT) quantitative PCR (qPCR) with nested primers, a synthetic
      nucleotide standard and SYBR Green I detection. Blood samples from volunteers
      with and without pituitary disorders were collected in PAXgene Blood RNA tubes.
      Essential MIQE guidelines were followed during sample preparation and assay
      development. RESULTS: RT-qPCR assay was specific for GH mRNA and was linear from
      <= 90 to >= 90,000 copies of GH mRNA per reaction. Day-to-day imprecision (CV)
      was 31%-46% at mean concentrations of 3400 and 2630 copies/mL of blood,
      respectively (n=10). The variability (CV) of results in samples collected from a
      single individual over a year and assayed in a single run was 28% (n=17 samples).
      The mean concentrations of GH mRNA in blood were statistically indistinguishable
      in patients with acromegaly, control subjects, and patients receiving replacement
      doses of recombinant GH. Moreover, GH mRNA concentrations in blood were not
      correlated with concentrations of insulin-like growth factor-I in plasma.
      CONCLUSIONS: The RT-PCR assay quantifies GH mRNA at concentrations present in
      circulating cells. The present study suggests that the absolute concentration of
      GH mRNA in circulating cells is not altered in patients with acromegaly.

PMID- 22985688
TI  - Reverse-hybridization assay for rapid detection of common CYP21A2 mutations in
      dried blood spots from newborns with elevated 17-OH progesterone.
AB  - BACKGROUND: Congenital adrenal hyperplasia (CAH) is an autosomal recessive
      disorder most commonly caused by defects in the CYP21A2 gene. Neonatal CAH
      screening based on 17-hydroxyprogesterone (17-OHP) measurements prevents life
      threatening salt wasting conditions in newborns, but results in a considerable
      false-positive rate. Therefore, efficient second tier tests are required.
      METHODS: We developed a reverse-hybridization test strip-based assay (CAH
      StripAssay) covering the most prevalent CYP21A2 point mutations/small
      insertions/deletions occurring in Middle European populations. Assay specificity
      was validated using plasmid clones, and wild-type and mutant reference DNAs. Its
      practicability was evaluated in 271 samples from patients with CAH, suspected
      CAH, and dried blood spots from screening-positive newborns. RESULTS: All eleven
      point mutations and 51% of large deletions/conversions could be unambiguously
      identified when compared to reference methods (DNA sequencing, MLPA). After
      exclusion of rare mutations (6.4%) not covered by the StripAssay, the overall
      detection rate was 85%. Undetected heterozygous deletions/conversions caused a
      lack of information, but did not result in an incorrect prediction of phenotypes.
      CONCLUSIONS: Our novel CAH StripAssay proved to be a fast (7h) and reliable
      method for detection of common CYP21A2 mutations. Implemented as a second-tier
      test in CAH newborn screening, it has the potential to significantly reduce
      recall rates.

PMID- 22985690
TI  - Astrocyte proliferation is regulated by the OGF-OGFr axis in vitro and in
      experimental autoimmune encephalomyelitis.
AB  - Astrocytes become activated and proliferate in response to autoimmune diseases
      involving the CNS. In many cases, elevated numbers of astrocytes may compound
      inflammatory responses and exacerbate neuronal degeneration. The regulation of
      astrocytes in disease states has been shown as an important corollary to disease
      progression and recovery. This study explores the role of the opioid growth
      factor (OGF)-OGF receptor (OGFr) axis in the proliferation of primary cultures of
      mouse cerebral astrocytes, as well as in spinal cord astrocytes of mice with
      experimental autoimmune encephalomyelitis (EAE), the animal model of multiple
      sclerosis. OGF was found to inhibit purified cultures of cortical astrocytes in a
      dose-related, receptor-mediated, and reversible manner. Examination of a number
      of endogenous opioid peptides supported that OGF was the most effective inhibitor
      of astrocyte proliferation and that endogenous production of this peptide was
      neutralized by OGF antibodies. The specificity and requirement for OGFr to be
      present and functional was indicated by studies using siRNA technology to
      knockdown the classical MU, delta, and kappa opioid receptors, as well as OGFr.
      Only knockdown of OGFr resulted in changes in astrocyte cell number with OGF
      rendered ineffective without the presence of OGFr. Astrocyte migration as studied
      by a scratch model, as well as apoptosis and necrosis pathways, were not altered
      by OGF treatment. However, BrdU incorporation during DNA synthesis phases of the
      cell cycle was significantly repressed in activated cultured astrocytes by OGF
      exposure. Overall activation of the astrocytes measured by nitric oxide levels
      was reduced, but proportional to the reduction in cell number. Examination of
      spinal cord tissues from mice with EAE revealed fewer astrocytes within 10 days
      of OGF treatment, with the mechanism of cell number reduction being repression of
      DNA synthesis. In conclusion, these studies delineate a novel role for OGF in the
      proliferation of mouse cortical astrocytes in vitro and spinal cord astrocytes in
      vivo, and support the use of OGF as a therapy to inhibit astrogliosis within a
      broad spectrum of autoimmune diseases.

PMID- 22985691
TI  - Effect of allergy and inflammation on eicosanoid gene expression in CFTR
      deficiency.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a complicating
      factor in cystic fibrosis (CF), affecting 2-15% of patients. We hypothesized that
      sensitization/challenge of CFTR(-/-) mice with an Aspergillus fumigatus (Af)
      extract will affect eicosanoid pathway gene expression, impacting ABPA and CF.
      METHODS: FABP-hCFTR(+/-)-CFTR(-/-) mice were sensitized/challenged with an Af
      extract and gene expression of lung mRNA was evaluated for >40 genes, with
      correlative data in human CF (IB3.1) and CFTR-corrected (S9) bronchoepithelial
      cell lines. RESULTS: Pla2g4c, Pla2g2c, Pla2g2d and Pla2g5 were induced in
      response to Af in CFTR(-/-) mice. Interestingly, PLA2G2D was induced by LPS, IL
      2, IL-6, IL-13, and Af only in CFTR-deficient human IB3.1 cells. Prostanoid gene
      expression was relatively constant, however, several 12/15-lipoxygenase genes
      were induced in response to Af. Numerous cytokines also caused differential
      expression of ALOX15 only in IB3.1 cells. CONCLUSIONS: The distinct regulation of
      PLA2G4C, PLA2G2D and ALOX15 genes in Aspergillus sensitization and/or cystic
      fibrosis could provide new insights into diagnosis and treatment of ABPA and CF.

PMID- 22985693
TI  - Origin of pisatin demethylase (PDA) in the genus Fusarium.
AB  - Host specificity of plant pathogens can be dictated by genes that enable
      pathogens to circumvent host defenses. Upon recognition of a pathogen, plants
      initiate defense responses that can include the production of antimicrobial
      compounds such as phytoalexins. The pea pathogen Nectria haematococca mating
      population VI (MPVI) is a filamentous ascomycete that contains a cluster of genes
      known as the pea pathogenicity (PEP) cluster in which the pisatin demethylase
      (PDA) gene resides. The PDA gene product is responsible for the detoxification of
      the phytoalexin pisatin, which is produced by the pea plant (Pisum sativum L.).
      This detoxification activity allows the pathogen to evade the phytoalexin defense
      mechanism. It has been proposed that the evolution of PDA and the PEP cluster
      reflects horizontal gene transfer (HGT). Previous observations consistent with
      this hypothesis include the location of the PEP cluster and PDA gene on a
      dispensable portion of the genome (a supernumerary chromosome), a
      phylogenetically discontinuous distribution of the cluster among closely related
      species, and a bias in G+C content and codon usage compared to other regions of
      the genome. In this study we compared the phylogenetic history of PDA, beta
      tubulin, and translation elongation factor 1-alpha in three closely related fungi
      (Nectria haematococca, Fusarium oxysporum, and Neocosmospora species) to formally
      evaluate hypotheses regarding the origin and evolution of PDA. Our results,
      coupled with previous work, robustly demonstrate discordance between the gene
      genealogy of PDA and the organismal phylogeny of these species, and illustrate
      how HGT of pathogenicity genes can contribute to the expansion of host
      specificity in plant-pathogenic fungi.

PMID- 22985695
TI  - Cerebrospinal fluid neuropeptide Y-like immunoreactivity correlates with
      impulsive aggression in human subjects.
AB  - BACKGROUND: Neurochemical studies have pointed to a modulatory role in human
      aggression for a number of central neurotransmitters; some (e.g., serotonin)
      appear to play an inhibitory role, while others (e.g., vasopressin) appear to
      play a facilitator role in the modulation of aggression. While recent animal
      studies of neuropeptide Y (NPY) have suggested a facilitator role for central NPY
      in the modulation of aggression, no human studies of central NPY have yet been
      reported regarding aggression. METHODS: Basal lumbar cerebrospinal fluid (CSF)
      was obtained from 60 physically healthy subjects with personality disorder (PD)
      (n=40) and from healthy volunteers (n=20). These samples were then assessed for
      CSF NPY-like immunoreactivity (NPY-LI) and other neurotransmitter-related species
      in CSF and correlated with measures of aggression and impulsivity. RESULTS:
      Cerebrospinal fluid NPY-LI was higher in PD subjects compared with healthy
      volunteers and in subjects with intermittent explosive disorder compared with
      those without intermittent explosive disorder. In PD subjects, CSF NPY-LI was
      directly correlated with composite measures of aggression and impulsivity and a
      composite measure of impulsive aggression. Group differences in CSF NPY-LI
      concentration were accounted for by measures of impulsive aggression.
      CONCLUSIONS: These data suggest a direct relationship between CSF NPY
      immunoreactivity concentration and measures of impulsive aggression in human
      subjects. This adds to the complex picture of the central neuromodulatory role of
      impulsive aggression in human subjects.

PMID- 22985696
TI  - Discriminative inhibitory control of cocaine seeking involves the prelimbic
      prefrontal cortex.
AB  - BACKGROUND: Recent neuroimaging studies have shown that people with cocaine
      addiction retain some degree of control over drug craving that correlates with
      neural activity in the lateral prefrontal cortex (PFC). Here, we report similar
      findings in a rat model of inhibitory control of cocaine seeking. METHODS: Rats
      actively responding for cocaine were trained to stop responding when presented
      with a discriminative stimulus that signaled lack of reinforcement. Rats were
      then tested for inhibitory control of cocaine seeking in novel behavioral
      contexts and in circumstances when cocaine seeking is particularly intense (e.g.,
      following drug priming). The role of neuronal activity in different subregions of
      the PFC was assessed using local pharmacologic inactivation and c-Fos
      immunohistochemistry. RESULTS: Rats progressively acquired the ability to stop
      cocaine seeking, even during drug intoxication and after a long history of
      cocaine self-administration. Inhibitory control of cocaine seeking was flexible,
      sufficiently strong to block cocaine-primed reinstatement, and selectively
      depended on increased neuronal activity within the prelimbic PFC, which is
      considered the rodent functional homolog of the human lateral PFC. CONCLUSIONS:
      Parallel evidence in both animal models and humans indicate that recruitment of
      prefrontal inhibitory control of drug seeking is still functional after prolonged
      cocaine use. Preclinical investigation of the mechanisms underlying this capacity
      may contribute to designing new behavioral and/or pharmacologic strategies to
      promote its use for the prevention of relapse in addiction.

PMID- 22985694
TI  - Impairment in semantic retrieval is associated with symptoms in schizophrenia but
      not bipolar disorder.
AB  - BACKGROUND: The Semantic Object Retrieval Task (SORT) requires participants to
      indicate whether word pairs recall a third object. Schizophrenia individuals (SZ)
      tend to report associations between nonassociated word pairs; this overretrieval
      is related to formal thought disorder (FTD). Since semantic memory impairments
      and psychosis are also found in bipolar disorder (BP), we examined whether SORT
      impairments and their relationship to symptoms are also present in BP. METHODS:
      Participants (n = 239; healthy control subjects [HC] = 133; BP = 32; SZ = 74)
      completed SORT while undergoing functional magnetic resonance imaging (fMRI)
      scanning. RESULTS: Retrieval accuracy negatively correlated with negative
      symptoms and no-retrieval accuracy negatively correlated with FTD severity in SZ
      but not BP. Retrieval versus no-retrieval trials activated a distributed fronto
      parieto-temporal network; bilateral inferior parietal lobule (IPL) activity was
      larger in HC versus SZ and HC versus BP, with no difference in SZ versus BP.
      Right IPL activity positively correlated with positive and general psychosis
      symptoms in SZ but not BP. CONCLUSIONS: SZ reported more associations between
      unrelated word pairs than HC; this overretrieval increased with FTD severity.
      Schizophrenia individuals were also more likely to fail to find associations
      between related word pairs; this underretrieval increased with negative symptom
      severity. fMRI symptom correlations in IPL in SZ are consistent with arguments
      that IPL abnormality relates to loosening of associations in SZ. By comparison,
      BP showed intermediate impairments on SORT, uncorrelated with symptoms,
      suggesting that the relationship between SORT performance, fMRI activity, and
      psychotic symptoms is schizophrenia-specific.

PMID- 22985697
TI  - Structural modification of siRNA for efficient gene silencing.
AB  - Small interfering RNA (siRNA) holds a great promise for the future of genomic
      medicine because of its highly sequence-specific gene silencing and universality
      in therapeutic target. The medical use of siRNA, however, has been severely
      hampered by the inherent physico-chemical properties of siRNA itself, such as low
      charge density, high structural stiffness and rapid enzymatic degradation;
      therefore, the establishment of efficient and safe siRNA delivery methodology is
      an essential prerequisite, particularly for systemic administration. For an
      efficient systemic siRNA delivery, it is a critical issue to obtain small and
      compact siRNA polyplexes with cationic condensing reagents including cationic
      polymers, because the size and surface properties of the polyplexes are major
      determinants for achieving desirable in vivo fate. Unfortunately, synthetic siRNA
      is not easily condensed with cationic polymers due to its intrinsic rigid
      structure and low spatial charge density. Accordingly, the loose siRNA polyplexes
      inevitably expose siRNA to the extracellular environment during systemic
      circulation, resulting in low therapeutic efficiency and poor biodistribution. In
      this review, we highlight the innovative approaches to increase the size of siRNA
      via structural modification of the siRNA itself. The attempts include several
      methodologies such as hybridization, chemical polymerization, and micro- and nano
      structurization of siRNA. Due to its increased charge density and flexibility,
      the structured siRNA can produce highly condensed and homogenous polyplexes
      compared to the classical monomeric siRNA. As a result, stable and compact siRNA
      polyplexes can enhance serum stability and target delivery efficiency in vivo
      with desirable biodistribution. The review specifically aims to provide the
      recent progress of structural modification of siRNA. In addition, the article
      also briefly and concisely explains the improved physico-chemical properties of
      structured siRNA with respect to stability, condensation ability and gene
      silencing efficiency. 

PMID- 22985698
TI  - Unconventional microbial systems for the cost-efficient production of high
      quality protein therapeutics.
AB  - Both conventional and innovative biomedical approaches require cost-effective
      protein drugs with high therapeutic potency, improved bioavailability,
      biocompatibility, stability and pharmacokinetics. The growing longevity of the
      human population, the increasing incidence and prevalence of age-related diseases
      and the better comprehension of genetic-linked disorders prompt to develop
      natural and engineered drugs addressed to fulfill emerging therapeutic demands.
      Conventional microbial systems have been for long time exploited to produce
      biotherapeutics, competing with animal cells due to easier operation and lower
      process costs. However, both biological platforms exhibit important drawbacks
      (mainly associated to intracellular retention of the product, lack of post
      translational modifications and conformational stresses), that cannot be overcome
      through further strain optimization merely due to physiological constraints. The
      metabolic diversity among microorganisms offers a spectrum of unconventional
      hosts, that, being able to bypass some of these weaknesses, are under progressive
      incorporation into production pipelines. In this review we describe the main
      biological traits and potentials of emerging bacterial, yeast, fungal and
      microalgae systems, by comparing selected leading species with well established
      conventional organisms with a long run in protein drug production.

PMID- 22985699
TI  - Metalloproteinase 2 and 9 activity in the development of pancreatic cancer.
AB  - Pancreatic adenocarcinoma is the fourth most common cancer occurring in both
      women and men. In Poland, within the past ten years the number of deaths from
      pancreatic cancer increased by 29%.The aim of the study was to determine the
      correlation between the activity of metalloproteinase (MMP) 2 and 9 and
      progression and aggressiveness of pancreatic cancer. MATERIAL AND METHODS: Tissue
      samples were collected from 36 patients with diagnosed pancreatic adenocarcinoma
      who underwent Whipple resection. Tumor tissues were analyzed by gel zymography,
      zymography in situ and immunohistochemistry. RESULTS: The activity of MMPs was
      found mainly in cancer cells. Active form of MMP2 (62 kDa) was present in 88% of
      cases and MMP9 (83 kDa) in 38% of cases. By contrast, immunohistochemical
      staining revealed the presence of metalloproteinase 9 in all studied tissues. MMP
      activity was assessed against histological grade of the tumor. In the case of
      group G1 there was no activity of matrix metalloproteinase 9. By comparing the
      activity we concluded that the activity of MMPs in tumors with the highest degree
      of differentiation is significantly lower than in G2 and G3. Metalloproteinase 9
      expression analysis revealed no significant differences between the groups of
      various degrees of histological maturity. The level of expression did not differ
      between the groups N0 and N1. CONCLUSION: Lack of metalloproteinase 9 activity in
      group G1 may indicate that MMP9 is activated only in higher tumor grades. We have
      shown that an active form of MMP2 is found in all histological grades, which
      supports its involvement in the development of pancreatic cancer.
      Metalloproteinases are attractive target of anticancer therapy but not only the
      level of expression of metalloproteinases should be taken into account but also
      their level of activity and factors associated with their activation.

PMID- 22985692
TI  - Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: a comparative
      efficacy trial.
AB  - BACKGROUND: Open-label, parallel-group, international trial comparing aztreonam
      for inhalation solution (AZLI) and tobramycin nebulizer solution (TNS) for cystic
      fibrosis patients with airway Pseudomonas aeruginosa. METHODS: 273 patients (>= 6
      years); randomized to three 28-day courses (AZLI 75 mg [three-times/day] or TNS
      300 mg [twice/day]); 28 off-days separated each course. RESULTS: 268 patients
      were treated (AZLI/TNS: 136/132). Mean baseline FEV1 was 52% predicted. Mean
      relative changes after 1 course (AZLI: 8.35%; TNS: 0.55%; p<0.001) and mean
      actual changes across 3 courses (AZLI: 2.05%; TNS: -0.66%; p=0.002) indicated
      AZLI statistical superiority vs. TNS. AZLI-treated patients had fewer respiratory
      hospitalizations (p=0.044) and respiratory events requiring additional
      antipseudomonal antibiotics (p=0.004); both treatments were well tolerated. 133
      patients received 1 to 3 courses of AZLI treatment in the open-label extension
      period (28-day courses separated by 28 days off-treatment); lung function
      improvements were comparable regardless of whether patients had received TNS or
      AZLI in the preceding comparative period. CONCLUSIONS: AZLI demonstrated
      statistical superiority in lung function and a reduction in acute pulmonary
      exacerbations compared to TNS over 3 treatment courses (ClinicalTrials.gov:
      NCT00757237).

PMID- 22985700
TI  - Assessment of the knowledge of GPS considering the surgical treatment of obesity.
AB  - Bariatric surgery is currently the only effective treatment option for morbidly
      obese patients. There has been observed a considerable disproportion between the
      number of procedures conducted in Poland and the number of patients requiring
      such treatment. There are no studies assessing bariatric knowledge among general
      practitioners who play crucial role in polish health care system. The aim of the
      study was to assess the knowledge of general practitioners regarding bariatric
      surgery. MATERIAL AND METHODS: An anonymous questionnaire conducted among 282
      general practitioners in 2010-2011 during local educational conferences. The
      questionnaire consisted of 10 questions relating to fundamental issues of
      bariatric surgery. RESULTS: Only one twelfth (8.1%) of the general practitioners
      questioned knows the indications for bariatric surgery, can apply them, and has
      epidemiological awareness. 61.5% of general practitioners know the surgical
      procedures used for the treatment of obesity, whereas 58% of them show the
      knowledge of surgical technique in which they are performed. Only 23% of general
      practitioners were aware that bariatric surgery decreases cancer risk. 92% of the
      participants noticed a necessity of education regarding the surgical treatment of
      obesity. CONCLUSIONS: Bariatric knowledge among general practitioners is not
      adequate to scientific research results published during the last years. Most
      general practitioners who participated in our study are aware of that and are
      awaiting for educational programmes focused on this issue.

PMID- 22985701
TI  - Impact of fast-track concept elements in the classical pancreatic head resection
      (Kausch-Whipple procedure).
AB  - The aim of the study was to determine statistically significant factors with an
      impact on the early postoperative surgical outcome. MATERIAL AND METHODS: The
      influence of applied fast-track components on surgical results and early
      postoperative outcome in 143 consecutive Kausch-Whipple procedure patients was
      evaluated in a single-center retrospective analysis of a prospective collection
      of patient-associated pre-, peri- and postoperative data from 1997-2006. RESULTS:
      The in-hospital mortality rate was 2.8% (n=4). Fast-track measures were shown to
      have no effect on the morbidity rate in the multi-variate analysis. Over the
      study period, a decrease of intraoperative infusion volume from 14.2 mL/kg body
      weight/h in the first year to 10.7 mL/kg body weight/h in the last year was
      accompanied by an increase in patients requiring intraoperative catecholamines,
      up from 17% to 95%. The administration of ropivacain/sufentanil via thoracic peri
      dural catheter injection initiated in 2000 and now considered the leading
      analgesic method, was used in 95% of the cases in 2006. Early extubation rate
      rose from 16.6% to 57.9%. CONCLUSIONS: Fast-track aspects in the perioperative
      management have become more important in several surgical procedure even in those
      with a greater invasiveness such as Kausch-Whipple. However, such techniques used
      in peri-operative management of Kausch-Whipple pancreatic-head resections had no
      impact on the morbidity rate. In addition, the low in-hospital mortality rate was
      particularly attributed to surgical competence.

PMID- 22985702
TI  - Navigation with the use of intraoperative ultrasonography in videoscopic adrenal
      surgery.
AB  - The aim of the study was to assess the efficacy of intraoperative ultrasonography
      during videoscopic adrenalectomy. MATERIAL AND METHODS: The study was conducted
      in patients undergoing extraperitoneal videoscopic adrenalectomy for adrenal
      tumours in the Department of Endocrine, General and Vascular Surgery of the
      Medical University in Lodz in 2008-2011. RESULTS: The active group consisted of
      20 patients in whom navigation with the use of intraoperative ultrasonography
      (IOUS) was used in the course of surgery. The comparison group consisted of 46
      patients operated without the use of IOUS. In the active group, we managed to
      obtain a shorter time of surgery by almost 20 min (89.44 +/- 27.11 min vs 109.12
      +/- 33.88 min; p=0.034) and a shorter lesion access time by more than 15 min
      (28.61 +/- 14.93 min vs 45.98 +/- 20.44 min; p=0.002). Intraoperative blood loss
      was also significantly lower in the active group (86.11 +/- 157 ml vs 169.27 +/-
      201.04 ml; p=0.037). In contrast, the use of IOUS did not affect the
      hospitalisation time (4.39 +/- 3.27 days vs 3.83 +/- 3.67 days; p=0.227), the
      rate of intraoperative complications (0/18 vs 2/41; p=1) and the conversion rate
      (2/20 - 10% vs 5/46 - 10.87%; p=1). CONCLUSIONS: 1. Intraoperative
      ultrasonography is useful for determining the tumour relationship with the
      surrounding anatomical structures. 2. Intraoperative ultrasonography is a useful
      technique in the assessment of adrenal tumour infiltration of the surrounding
      tissues. 3. This technique facilitates finding the pathological lesion,
      shortening the time of access to the tumour and procedure duration (thus reducing
      the burden for the patient). 4. Reduced blood loss was also obtained owing to the
      use of IOUS.

PMID- 22985703
TI  - Epididymal cysts in childhood - conservative or surgical approach?
AB  - THE AIM OF THE STUDY: To decide on the accurate way of treatment and to establish
      criteria for operation in boys with pubertal epididymal cysts (ECs). MATERIAL AND
      METHODS: Results of scrotal ultrasound of 363 boys and adolescents, aged 2 months
      to 18 years, were reviewed retrospectively. RESULTS: Of all 363 patients with
      scrotal ultrasound 59 (16.2%) at mean age of 14.03 yrs had ECs. The EC incidence
      increased with age and 42 out of 124 boys (33.8%) older than 14 yrs had cysts
      (chi2=27.627, p=0.000). Out of 59 patients, in 30 (50.8%) cysts were diagnosed
      incidentally at the time of scrotal US, 29 boys (49.2%) presented with scrotal
      mass and/or pain. 31 patients with ECs (52.5%) underwent elective surgery and the
      remaining 28 boys (47.5%) received conservative treatment. The age of boys with
      ECs who underwent surgery ranged from 8 to 18 years (mean 14.32). The age range
      of patients treated conservatively was 7-18 (mean 13.71). There was no
      statistical difference in age between boys treated surgically and conservatively
      (t=0.924, p=0.36). ECs resolved in 17 patients out of 28 boys treated
      conservatively, in remaining 11 boys the size of cysts was stabile and they
      remain asymptomatic. Clinical and ultrasonographic follow-up were carried out
      from 11 months to 5 years. CONCLUSIONS: ECs are more common in older boys (over
      14 years). Management of ECs smaller than 10 mm should be conservative with
      clinical and ultrasound controls, leaving surgery for cysts increasing in size
      over 10 mm which did not involute with time.

PMID- 22985704
TI  - Langerhans cell histiocytosis with thyroid involvement in a 3 year-old child - a
      case report.
AB  - Langerhans cell histiocytosis (LCH), a monoclonal disease of histiocytes, may
      involve several organ systems but rarely primarily involves the thyroid gland.
      This report presents an extremely rare case of LCH of the thyroid in a 3-year-old
      boy who presented with a neck mass for several weeks. LCH of the thyroid should
      be considered in the differential diagnosis of a child with a thyroid mass.
      Pulmonary examination should be done in these patients.

PMID- 22985705
TI  - Melanoma of unknown primary as a cause of intestinal obstruction - a case
      description.
AB  - Melanoma of unknown primary applies to 1-8% of all diagnosed melanomas, whereas
      primary melanoma of the small intestine is a extremely rare case. One of the
      melanoma characteristics is its capability of forming metastases in the small
      intestine which very often are diagnosed during autopsy.We present a case report
      of diagnosed melanoma of unknown primary, whose first symptom was intestinal
      obstruction. Before admission to the hospital cause of intestinal obstruction,
      the patient didn't present any signs and symptoms. All typical localizations of
      primary melanoma were excluded during diagnostic procedure. Palliative right
      hemicolectomy and segmental small intestine resection were performed. There were
      no complications in the postoperative course. On the ninth day the patient was
      discharged from hospital.Quick identification and radical resection of melanoma
      metastases in the alimentary tract may improve the survival rate in this group of
      patients. Resection, even if it is palliative by assumption, is not only the best
      method of elimination of persistent symptoms but it also gives hope for longer
      survival.

PMID- 22985706
TI  - Lower limb trauma: limb salvage or an early amputation?

PMID- 22985707
TI  - Frequently missed abdominal compartment syndrome.

PMID- 22985708
TI  - Pulmonary hemorrhage in Henoch-Schonlein purpura: case report and systematic
      review of the english literature.
AB  - BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a rare complication of Henoch
      Schonlein purpura (HSP) and data on its prevalence, management, and outcomes are
      scant. OBJECTIVES: To enable evidence-based management of DAH in HSP. METHODS: A
      case report and a systematic review were conducted of all reported cases of DAH
      complicating HSP in the English literature. RESULTS: DAH predominantly affects
      older male children and adults with HSP. The occurrence of DAH in HSP is rare and
      the reported prevalence ranged from 0.8% to 5%. DAH occurred variably after the
      diagnosis of HSP, ranging from 2 days to 18 years. Hemoptysis (75%), drop in
      hemoglobin (74%), and chest infiltrates (94%) were the most common clinical
      findings. Lung biopsy showed leukocytoclastic vasculitis with alveolar hemorrhage
      (69.2%) or only alveolar hemorrhage (31.8%) with variable IgA staining by
      immunofluorescence. DAH was frequently severe and 50% of the patients required
      mechanical ventilation. Cyclophosphamide and pulse methylprednisolone for DAH was
      associated with better outcomes, particularly in patients who were already
      receiving steroids at the time of DAH. Steroids and immunosuppressants were
      administered for a median duration of 9 and 4.5 months, respectively. Systemic
      recurrences (27.7%) and recurrences of DAH (8.3%) were frequent. DAH was
      associated with high mortality (27.6%) and morbidity (persistent urinary
      abnormalities, 12%; chronic renal failure, 9%; complications of therapy, 27%).
      CONCLUSIONS: DAH is a life-threatening complication in HSP. Current protocols use
      pulse methylprednisolone and cyclophosphamide for 6 months.

PMID- 22985709
TI  - Evidence-based criteria for sarcopenia with clinically important weakness.

PMID- 22985710
TI  - A review of assertions about the processes and outcomes of social learning in
      natural resource management.
AB  - Social learning has become a central theme in natural resource management. This
      growing interest is underpinned by a number of assertions about the outcomes of
      social learning, and about the processes that support these outcomes. Yet
      researchers and practitioners who seek to engage with social learning through the
      natural resource management literature often become disorientated by the myriad
      processes and outcomes that are identified. We trace the roots of current
      assertions about the processes and outcomes of social learning in natural
      resource management, and assess the extent to which there is an emerging
      consensus on these assertions. Results suggest that, on the one hand, social
      learning is described as taking place through deliberative interactions amongst
      multiple stakeholders. During these interactions, it is argued that participants
      learn to work together and build relationships that allow for collective action.
      On the other hand, social learning is described as occurring through deliberate
      experimentation and reflective practice. During these iterative cycles of action,
      monitoring and reflection, participants learn how to cope with uncertainty when
      managing complex systems. Both of these processes, and their associated outcomes,
      are referred to as social learning. Where, therefore, should researchers and
      practitioners focus their attention? Results suggest that there is an emerging
      consensus that processes that support social learning involve sustained
      interaction between stakeholders, on-going deliberation and the sharing of
      knowledge in a trusting environment. There is also an emerging consensus that the
      key outcome of such learning is improved decision making underpinned by a growing
      awareness of human-environment interactions, better relationships and improved
      problem-solving capacities for participants.

PMID- 22985711
TI  - Polybrominated diphenyl ethers fate in China: a review with an emphasis on
      environmental contamination levels, human exposure and regulation.
AB  - Because of their highly effective flame-retardant capability, polybrominated
      diphenyl ethers (PBDEs) have been extensively used as flame retardants in
      consumer goods. However, compelling evidence shows that many congeners of PBDEs
      have been accumulating in the environment, in biota and in human populations
      worldwide. In China, although octabrominated diphenyl ether (octaBDE) has never
      been produced or used, pentabrominated diphenyl ether (pentaBDE) and
      decabrominated diphenyl ether (decaBDE) have been produced and used in large
      quantities. In the face of increasing evidence about PBDE pollution and the
      adoption of international conventions, there is a growing push for China to
      develop more stringent methods of managing PBDE waste. This paper summarizes the
      information about PBDE production and application, describes the flame-retarding
      mechanism, and then reviews the toxicity and levels of PBDEs in China's
      environmental media and human tissues. Based on international regulations on
      PBDEs, the paper finally puts forward some suggestions for Chinese policy making
      and for self-regulation within the flame retardant industry.

PMID- 22985712
TI  - Public perceptions of the response to the Deepwater Horizon oil spill: personal
      experiences, information sources, and social context.
AB  - The 2010 British Petroleum (BP) Deepwater Horizon oil spill highlighted long
      standing questions about energy exploration and its social and environmental
      implications. Sociologists studying environmental disasters have documented the
      social impacts resulting from these events and dissatisfaction with government
      and industry responses. In this paper, we use data from a survey conducted during
      the Gulf of Mexico oil spill to examine how Louisiana and Florida residents'
      social backgrounds, experiences with the spill, and trust in information sources
      predict their perceptions of governmental and BP response efforts. We find that
      direct personal impacts and compensation strongly influence the evaluations of
      responding organizations. Age and place of residence also predict such
      assessments. Finally, levels of confidence in television news and BP as sources
      of information appear to shape Gulf Coast residents' opinions about the work of
      organizations responding to the Deepwater Horizon disaster.

PMID- 22985713
TI  - Amputation for extremity soft tissue sarcoma does not increase overall survival:
      a retrospective cohort study.
AB  - To determine if amputation increases survival when compared to limb salvage
      surgery in patients with a soft tissue sarcoma (STS) of the extremity when there
      is often a misconception among physicians and patients that ablative surgery
      eliminates local recurrence and increases overall survival. This retrospective
      cohort study assessed 278 patients with STS and compared 18 patients who had
      undergone amputations for soft tissue sarcomas of the extremities to a
      comparative cohort of 260 patients who underwent limb salvage surgery during the
      same time period. Our limb salvage surgery (LSS) rate was 94% overall for soft
      tissue sarcomas with a median follow-up of 3.1 years. Patients undergoing
      amputations either had tumors that involved a critical neurovascular bundle (in
      particular nerve rather than vessel resection was more responsible for a decision
      toward ablation), or underlying bone or had neoplasms whose large size would
      require such an enormous resection that a functional limb would not remain. In
      comparing prognostic effects, mainly death due to sarcoma, distant metastasis and
      local recurrence, it was found that there was no statistically significant
      difference between patients undergoing amputation to those undergoing limb
      salvage surgery (p > 0.05). While amputations do not increase overall survival in
      soft tissue sarcomas of the extremity as compared to LSS, they are still a
      valuable option in a surgeon's arsenal. In particular, amputations can provide
      improved local control and symptomatic treatment in patients who might not be
      candidates for limb salvage surgery.

PMID- 22985714
TI  - Ethical considerations in embedding a surgeon in a military or civilian tactical
      team.
AB  - Tactical emergency medical services (TEMS) bring immediate medical support to the
      inner perimeter of special weapons and tactics team activations. While initially
      envisioned as a role for an individual dually trained as a police officer and
      paramedic, TEMS is increasingly undertaken by physicians and paramedics who are
      not police officers. This report explores the ethical underpinnings of embedding
      a surgeon within a military or civilian tactical team with regard to identity,
      ethically acceptable actions, triage, responsibility set, training,
      certification, and potential future refinements of the role of the tactical
      police surgeon.

PMID- 22985715
TI  - Production and purification of theVP1 capsid protein of a novel canine norovirus
      using the Saccharomyces cerevisiae expression system.
AB  - The discovery of a novel canine norovirus was recently reported. The VP1 capsid
      protein of this canine norovirus was expressed in Saccharomyces cerevisiae and
      purified with a yield of 1.6-1.8 mg/L. The yeast-expressed VP1 protein self
      assembled into virus-like particles and exhibited antigenicity, proving to be
      suitable for serological assays.

PMID- 22985716
TI  - An enhanced technique combining pre-enrichment and passive filtration increases
      the isolation efficiency of Campylobacter jejuni and Campylobacter coli from
      water and animal fecal samples.
AB  - Improved isolation techniques from environmental water and animal samples are
      vital to understanding Campylobacter epidemiology. In this study, the efficiency
      of selective enrichment in Bolton Broth (BB) followed by plating on charcoal
      cefoperazone deoxycholate agar (CCDA) (conventional method) was compared with an
      approach combining BB enrichment and passive filtration (membrane method) adapted
      from a method previously developed for testing of broiler meat, in the isolation
      of thermophilic campylobacters from surface water and animal fecal samples. The
      conventional method led to recoveries of Campylobacter from 36.7% of the water
      samples and 78.0% of the fecal samples and similar numbers, 38.3% and 76.0%,
      respectively, were obtained with the membrane method. To investigate the genetic
      diversity of Campylobacter jejuni and Campylobacter coli obtained by these two
      methods, isolates were analyzed using Comparative Genomic Fingerprinting, a high
      resolution subtyping technique. The conventional and membrane methods yielded
      similar numbers of Campylobacter subtypes from water (25 and 28, respectively)
      and fecal (15 and 17, respectively) samples. Although there was no significant
      difference in recovery rates between the conventional and membrane methods, a
      significant improvement in isolation efficiency was obtained by using the
      membrane method, with a false-positive rate of 1.6% compared with 30.7% obtained
      using the conventional method. In conclusion, although the two methods are
      comparable in sensitivity, the membrane method had higher specificity, making it
      a cost-effective procedure for the enhanced isolation of C. jejuni and C. coli
      from water and animal fecal samples.

PMID- 22985717
TI  - Rapid quantification of pathogenic fungi by Cellometer image-based cytometry.
AB  - The objective of this study was to develop an image-based cytometric methodology
      for the quantification of viable pathogenic yeasts, which can offer increased
      sensitivity and efficiency when compared to the traditional colony forming unit
      (CFU) assay. Live/dead yeast quantification by flow cytometry has been previously
      demonstrated, however, adoption of flow cytometric detection of pathogenic yeasts
      has been limited for a number of practical reasons including its high cost and
      biosafety considerations. Our studies focus on detection of two human fungal
      pathogens: Histoplasma capsulatum and Candida albicans. H. capsulatum colonizes
      alveolar macrophages by replicating within the macrophage phagosome. Here, we
      quantitatively assess the growth of H. capsulatum yeasts within RAW 264.7
      macrophages using acridine orange/propidium iodide staining in combination with
      Cellometer image-based cytometry; this method faithfully recapitulates growth
      trends as measured by traditional CFU enumeration, but with significantly
      increased sensitivity. Additionally, we directly assess infection of bone marrow
      derived macrophages with a GFP-expressing strain of C. albicans. To demonstrate
      that image-based cytometry can be used as a tool to assess the susceptibility of
      fungi to antifungal drugs, we perform dose response experiments with the
      antifungal drugs amphotericin B and itraconazole and show that image-based
      cytometry allows rapid assessment of the kinetics of cytotoxicity induced by
      these antifungals. Our methodology offers a rapid, accurate, and economical means
      for detection and quantification of important human fungal pathogens, either
      alone or in association with host cells.

PMID- 22985718
TI  - An improved high-throughput Nile red fluorescence assay for estimating
      intracellular lipids in a variety of yeast species.
AB  - A rapid and inexpensive method for estimating lipid content of yeasts is needed
      for screening large numbers of yeasts samples. Nile red is a fluorescent
      lipophilic dye used for detection and quantification of intracellular lipid
      droplets in various biological system including algae, yeasts and filamentous
      fungi. However, a published assay for yeast is affected by variable diffusion
      across the cell membrane, and variation in the time required to reach maximal
      fluorescence emission. In this study, parameters that may influence the emission
      were varied to determine optimal assay conditions. An improved assay with a high
      throughput capability was developed that includes the addition of dimethyl
      sulfoxide (DMSO) solvent to improve cell permeability, elimination of the washing
      step, the reduction of Nile red concentration, kinetic readings rather than
      single time-point reading, and utilization of a black 96-well microplate. The
      improved method was validated by comparison to gravimetric determination of lipid
      content of a broad variety of ascomycete and basidiomycete yeast species.

PMID- 22985719
TI  - Biophysical characterization of higher plant Rubisco activase.
AB  - Rubisco activase (Rca) is a chaperone-like protein of the AAA+ family, which uses
      mechano-chemical energy derived from ATP hydrolysis to release tightly bound
      inhibitors from the active site of the primary carbon fixing enzyme ribulose 1,5
      bisphosphate oxygenase/carboxylase (Rubisco). Mechanistic and structural
      investigations of Rca have been hampered by its exceptional thermolability, high
      degree of size polydispersity and propensity towards subunit aggregation. In this
      work, we have characterized the thermal stability and self-association behavior
      of recombinant Rca preparations, and have developed ligand screening methods.
      Thermal denaturation profiles generated by circular dichroism indicate that
      creosote and tobacco short-form Rcas are the most stable proteins examined, with
      an estimated mid-point temperature of 45-47 degrees C for protein denaturation.
      We demonstrate that ADP provides a higher degree of stabilization than ATP, that
      magnesium ions have a small stabilizing effect on ATP-bound, but a significant
      destabilizing effect on ADP-bound Rca, and that phosphate provides weak
      stabilization of the ADP-bound form of the protein. A dimeric species was
      identified by size-exclusion chromatography, suggesting that the two-subunit
      module may comprise the basic building block for larger assemblies. Evidence is
      provided that chromatographic procedures reflect non-equilibrium multimeric
      states. Dynamic light scattering experiments performed on nucleotide-bearing Rca
      support the notion that several larger, highly polydisperse assembly states
      coexist over a broad concentration range. No significant changes in aggregation
      are observed upon replacement of ADP with ATP. However, in the absence of
      nucleotides, the major protein population appears to consist of a monodisperse
      oligomer smaller than a hexamer.

PMID- 22985720
TI  - Cognitive enhancers: molecules, mechanisms and minds.

PMID- 22985721
TI  - Growth during infancy and childhood, and adiposity at age 16 years: ages 2 to 7
      years are pivotal.
AB  - OBJECTIVE: To assess the period during infancy and childhood in which growth is
      most associated with adolescent adiposity and the metabolic syndrome (MS) and
      whether this differs depending on maternal smoking during pregnancy. STUDY
      DESIGN: A longitudinal population-based cohort study among 772 girls and 708
      boys. RESULTS: Weight gains between ages 2-4 years and ages 4-7 years were most
      strongly associated with higher body mass index (BMI), sum of skinfold
      measurements, body fat percentage, and waist circumference at age 16. A one SD
      increase in weight between ages 2-4 and 4-7 years was associated with increases
      in outcome measures of +0.82 to +1.47 SDs (all P < .001), and with a less
      favorable MS score. In children whose mothers smoked during pregnancy, the
      association of relative weight gain during ages 2-4 years with adolescent BMI was
      stronger than in children whose mothers did not smoke. For adolescent BMI, the
      increase was 0.42 SD higher (P = .01). This was similar for the other adiposity
      measures. CONCLUSIONS: Large relative increases in weight from ages 2 to 7 years
      are associated with adolescent adiposity and MS. This is more pronounced in
      adolescents whose mothers smoked during pregnancy.

PMID- 22985724
TI  - Respiratory outcome in children with scimitar syndrome.
AB  - OBJECTIVE: To evaluate respiratory morbidities and lung function tests in the
      cohort of patients with scimitar syndrome evaluated at our center since 1976.
      STUDY DESIGN: Eighty-one children were investigated. Twenty-six patients died,
      all with the infantile form. The median duration of follow-up of surviving
      children was 7.2 years. RESULTS: A high rate of respiratory morbidities was
      measured, with 38% and 43% of children reporting pulmonary infections or wheezing
      episodes during the last 12 months of follow-up, respectively. One-third of
      children have been rehospitalized for a respiratory cause. Lung function tests
      were obtained in 20 children. The median value of total lung capacity was 73.0%
      of the predicted value (IQR, 65.3-86.8), and the median value of the ratio of the
      forced expiratory volume in one second to the forced vital capacity was -1.26 Z
      score (-2.25; -0.31). Significantly lower total lung capacity values were
      obtained in children with the infantile form (P < .005) or with a history of
      thoracic surgery (P = .002). The ratio of the forced expiratory volume in one
      second to the forced vital capacity Z score values were significantly lower in
      boys (P < .05) and in children with a history of wheezing (P = .01). Wheezing
      episodes were not associated with significant salbutamol-induced reversibility.
      CONCLUSION: Respiratory complications frequently are observed in children with
      scimitar syndrome. Pulmonary hypoplasia appears as an independent marker of long
      term severity in these patients.

PMID- 22985722
TI  - Cerebrospinal fluid findings in children with fever-associated status
      epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT)
      study.
AB  - This prospective multicenter study of 200 patients with fever-associated status
      epilepticus (FSE), of whom 136 underwent a nontraumatic lumbar puncture, confirms
      that FSE rarely causes cerebrospinal fluid (CSF) pleocytosis. CSF glucose and
      protein levels were unremarkable. Temperature, age, seizure focality, and seizure
      duration did not affect results. CSF pleocytosis should not be attributed to FSE.

PMID- 22985723
TI  - Effects of maternal sensitivity and cognitive and linguistic stimulation on
      cochlear implant users' language development over four years.
AB  - OBJECTIVES: To examine the effects of observed maternal sensitivity (MS),
      cognitive stimulation (CS), and linguistic stimulation on the 4-year growth of
      oral language in young, deaf children receiving a cochlear implant. Previous
      studies of cochlear implants have not considered the effects of parental
      behaviors on language outcomes. STUDY DESIGN: In this prospective, multisite
      study, we evaluated parent-child interactions during structured and unstructured
      play tasks and their effects on oral language development in 188 deaf children
      receiving a cochlear implant and 97 normal-hearing children as controls. Parent
      child interactions were rated on a 7-point scale using the National Institute of
      Child Health and Human Development's Early Childcare Study codes, which have well
      established psychometric properties. Language was assessed using the MacArthur
      Bates Communicative Development Inventories, the Reynell Developmental Language
      Scales, and the Comprehensive Assessment of Spoken Language. RESULTS: We used
      mixed longitudinal modeling to test our hypotheses. After accounting for early
      hearing experience and child and family demographics, MS and CS predicted
      significant increases in the growth of oral language. Linguistic stimulation was
      related to language growth only in the context of high MS. CONCLUSION: The
      magnitude of effects of MS and CS on the growth of language was similar to that
      found for age at cochlear implantation, suggesting that addressing parenting
      behaviors is a critical target for early language learning after implantation.

PMID- 22985725
TI  - Modern approach for determination of lactulose, mannitol and sucrose in human
      urine using HPLC-MS/MS for the studies of intestinal and upper digestive tract
      permeability.
AB  - A new analytical procedure was described for the simultaneous determination of
      lactulose, mannitol and sucrose in urine, in which HILIC chromatography and
      tandem mass spectrometry detection are used. Sugars are orally administered for
      the estimation of intestinal permeability in children digestive tract. Samples
      were purified by dispersive solid phase extraction (d-SPE) using Amberlite MB150
      resin. Raffinose was selected as an internal standard. The chosen chromatographic
      separation was carried out on ZIC((r))-HILIC column in 10 min at a flow rate of
      0.3 mL/min, using mixture of acetonitrile (ACN) and ammonium acetate (NH(4)Ac) in
      water (H(2)O) as the mobile phase. Within-run precision (CV) measured at three
      concentrations was 1.08%, 0.32% and 0.49% for lactulose; 1.88%, 0.47% and 0.75%
      for mannitol, 2.95%, 1.31% and 0.6% for sucrose. Between-run CVs were 0.75%, 1.1%
      and 1.2% for lactulose; 1.1%, 1.02% and 1.01% for mannitol; 1.17%, 1.4% and 1.05%
      for sucrose. Analytical recovery of all three sugar probes was 95.06-99.92%. The
      detection limits were: 15.94 ng/mL for lactulose, 17.10 ng/mL for sucrose and
      11.48 ng/mL for mannitol. The proposed method is rapid, simple, sensitive and
      suitable for the determination of intestinal permeability of the sugar
      derivatives in children.

PMID- 22985726
TI  - A routine method for cholesterol and 7-dehydrocholesterol analysis in dried blood
      spot by GC-FID to diagnose the Smith-Lemli-Opitz syndrome.
AB  - This work was aimed to implement a fast and simple method to quantify cholesterol
      (CHOL) and 7-dehydrocholesterol (7-DHC) in dried blood spot (DBS) to diagnose the
      Smith-Lemli-Opitz syndrome (SLOS), an inborn error of CHOL biosynthesis. We
      developed and validated a GC-FID method for separation and quantification of
      underivatized CHOL and 7-DHC using a DBS disc of 6mm with a run time of 9 min.
      Correlation coefficients (r) of calibration curves ranged from 0.998 to 0.999 for
      CHOL and from 0.997 to 0.998 for 7-DHC. Within-day and between-day imprecision
      (CV%), accuracy (%), carry-over, and extraction efficacy (%) were also evaluated
      for validation. CHOL and 7-DHC were analyzed in DBS and plasma samples from 8
      SLOS patients and 30 unaffected subjects. In SLOS patients, 7-DHC/CHOL ratios in
      DBS and plasma samples ranged from 0.035 to 1.448 and from 0.012 to 0.926,
      respectively. Results from calibration curves, quality controls and patient
      samples reveal that the method is suitable to analyze DBS to screen patients
      affected by SLOS.

PMID- 22985727
TI  - Complete monosomy mosaic of chromosome 21: case report and review of literature.
AB  - Complete monosomy mosaic of chromosome 21 is a rare disorder. The syndromic
      features are highly variable. This study describes a girl of Mexican origin with
      complete monosomy 21 in mosaicism with novel findings, including cortical
      atrophy, macrostomia, pectum excavatum and immune deficiencies. Parental
      karyotypes were normal. FISH analysis with probes from 21q22.1-q22.2 region and
      centromere of X DNA probe was performed on peripheral blood lymphocytes whereas
      21q22.1-q22.2 and 21q, 4p, 4q subtelomeric DNA probes were tested in fibroblasts.
      We propose that the monosomy 21 mosaicism is the cause of the survival of
      children with more than 4 months of age.

PMID- 22985728
TI  - Sonography as an objective tool for monitoring serial corrections and detecting
      spurious corrections in clubfoot: a review.
AB  - Ultrasonography is an emerging tool for monitoring clubfoot correction and for
      early diagnosis of spurious correction and of deformity recurrence. Sonography is
      widely available, inexpensive and has dynamic capability and can visualize
      tarsals in infants accurately.

PMID- 22985729
TI  - Traumatic loss of talus: a rare injury.
AB  - BACKGROUND: Traumatic loss of talus during a compound injury of ankle is an
      unusual injury. OBJECTIVE: We report a 55 years old woman who sustained an open
      ankle injury with complete extrusion of talus and loss at the injury site.
      METHOD: A tricortical bone graft was obtained from iliac crest and talar
      dimensions carved with 5 cm length and 3 cm height given by buttressing fibular
      graft between them. These grafts are made in the shape of talus by fixing them
      together with cortical screw and binding them together with Ethibond No. 5. By
      anterior approach ankle was opened and talar graft was placed in between the raw
      surfaces of tibia and calcaneus to facilitate ankle arthrodesis. RESULT: Patient
      had solid fusion at the ankle joint after 4 months with no pain on walking.
      CONCLUSION: The definitive treatment of this serious lower extremity injury
      remains controversial we have attempted this novel way of treatment as the
      patient was unable to afford talar prosthesis and facilities of allogenic bone
      grafts were not there.

PMID- 22985731
TI  - Bleeding diathesis in Noonan syndrome: is acquired von Willebrand syndrome the
      clue?
AB  - INTRODUCTION: Noonan syndrome (NS) is characterized by dysmorphic facies, short
      stature and congenital heart defects. Various haemostatic disorders have been
      described in NS patients, but not all were related to bleeding, which itself is
      present in up to 65%. Several subgroups of NS - especially those with PTPN11
      mutation - are associated with pulmonary stenosis. As it is known that some heart
      defects are prone to a shear stress related destruction of the von Willebrand
      factor as an important haemostatic component, we aimed to find out, whether the
      pulmonary stenosis could be responsible for such a mechanism in NS patients.
      PATIENTS, METHODS AND RESULTS: We investigated the haemostatic system in 15
      children with genetically proven NS (14 with PTPN11, one with SOS1 mutation).
      Platelet count, basic coagulation parameters, fibrinogen and antithrombin were
      normal in all patients, none had a relevant reduction of coagulation factor
      activities. Five patients had pulmonary valve stenosis with systolic gradients>60
      mmHg. In three of them a deficiency of the high molecular weight multimers and a
      pathologic collagen-binding capacity were detected, suggesting acquired von
      Willebrand syndrome. Nine of our patients indicated a relevant bleeding diathesis
      and complained of easy bruising, three reported spontaneous gum bleeding. IN
      CONCLUSION: the destruction of the von Willebrand factor could explain the
      bleeding in some of the NS patients with pulmonary valve stenosis. Our finding is
      of clinical relevance since most of these patients require either interventional
      cardiac catheterization or open heart surgery which may be complicated by the
      haemorrhagic tendency.

PMID- 22985730
TI  - TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in
      nonsensory cochlear epithelium by ATOH1.
AB  - Transcription factors (TFs) can regulate different sets of genes to determine
      specific cell types by means of combinatorial codes. We previously identified
      closely-spaced TF binding motifs located 8.2-8.5 kb 5' to the ATG of the murine
      Pou4f3 gene, a gene required for late hair cell (HC) differentiation and
      survival. These motifs, 100% conserved among four mammalian species, include a
      cluster of E-boxes preferred by TCF3/ATOH1 heterodimers as well as motifs for
      GATA factors and SP1. We hypothesized that these factors might interact to
      regulate the Pou4f3 gene and possibly induce a HC phenotype in non-sensory cells
      of the cochlea. Cochlear sensory epithelium explants were prepared from postnatal
      day 1.5 transgenic mice in which expression of GFP is driven by 8.5 kb of Pou4f3
      5' genomic DNA (Pou4f3/GFP). Electroporation was used to transfect cells of the
      greater epithelial ridge with multiple plasmids encoding human ATOH1 (hATOH1),
      hTCF3 (also known as E2A or TEF2), hGATA3, and hSP1. hATOH1 or hTCF3 alone
      induced Pou4f3/GFP cells but hGATA3 and hSP1 did not. hATOH1 but not hTCF3
      induced conversion of greater epithelial ridge cells into Pou4f3/GFP and myosin
      VIIa double-positive cells. Transfection of hATOH1 in combination with hTCF3 or
      hGATA3 induced 2-3X more Pou4f3/GFP cells, and similarly enhanced Pou4f3/GFP and
      myosin VIIa double-positive cells, when compared to hATOH1 alone. Triple or
      quadruple TF combinations were generally not more effective than double TF
      combinations except in the middle turn, where co-transfection of hATOH1, hE2A,
      and hGATA3 was more effective than hATOH1 plus either hTCF3 or hGATA3. The
      results demonstrate that TFs can cooperate in regulation of the Pou4f3 gene and
      in the induction of at least one other element of a HC phenotype. Our data
      further indicate that combinations of TFs can be more effective than individual
      TFs in the inner ear.

PMID- 22985732
TI  - Acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, is controlled by
      SREBP-2 and affects serum cholesterol levels.
AB  - Ketone bodies have been regarded as an energy source that is mainly produced in
      the liver, and exported to extrahepatic tissues. However, ketone bodies have also
      been suggested to be used during the lipogenesis by the ketone body-utilizing
      enzyme, acetoacetyl-CoA synthetase (AACS). To elucidate the physiological role of
      AACS in the liver, we investigated the mechanism of transcription of the AACS
      gene and performed knockdown experiments. We showed that SREBP-2 regulates the
      expression of AACS and that knockdown of AACS in vivo, by the hydrodynamics
      method, resulted in the reduction of total blood cholesterol. These results
      suggest that ketone body metabolism via AACS activity plays an important role in
      cholesterol homeostasis.

PMID- 22985733
TI  - Anterior inferior iliac spine deformity as an extra-articular source for hip
      impingement: a series of 10 patients treated with arthroscopic decompression.
AB  - PURPOSE: To describe an arthroscopic technique for decompression of a prominent
      anterior inferior iliac spine (AIIS) leading to extra-articular hip impingement
      and to provide short-term outcome after this procedure. METHODS: We
      retrospectively reviewed office charts, imaging studies, operative reports,
      arthroscopic images, preoperative and postoperative hip flexion range of motion,
      and preoperative and postoperative modified Harris Hip Scores in a consecutive
      series of 10 male patients who had arthroscopic decompression of symptomatic AIIS
      deformities leading to extra-articular hip impingement. The procedure was
      performed through standard anterolateral and mid-anterior hip arthroscopy portals
      that were also used to explore the joint and address concomitant intra-articular
      pathologies. RESULTS: The mean age was 24.9 years, with 8 of 10 patients aged
      younger than 30 years. In 9 patients, an anterior cam lesion was identified and
      decompressed before the AIIS decompression. The mean follow-up time was 14.7
      months (range, 6 to 26 months). Hip flexion range of motion improved from 99
      degrees  +/- 7 degrees  before surgery to 117 degrees  +/- 8 degrees  after
      surgery (P < .001). The modified Harris Hip Score improved from 64 +/- 18 before
      surgery to 98 +/- 2 at latest follow-up after surgery (P < .001). CONCLUSIONS:
      Arthroscopic decompression of a symptomatic AIIS deformity is a reproducible
      procedure that can provide excellent outcomes at short-term follow-up. As opposed
      to using an open approach for decompressing a prominent AIIS, an arthroscopic
      approach may be of particular value in patients with mixed intra- and extra
      articular sources of hip dysfunction, because it enables the surgeon to address
      all pathologies with a single arthroscopic procedure. LEVEL OF EVIDENCE: Level
      IV, therapeutic case series.

PMID- 22985734
TI  - Musculoskeletal injuries among victims of the Battagram, Pakistan earthquake in
      October 2005.
AB  - OBJECTIVE: This study was conducted to assess the type, pattern, and severity of
      musculoskeletal injuries, as well as the type of simple orthopedic surgical
      procedures, that can be performed at the site of a disaster. METHODS: This was a
      cross-sectional study conducted in Battagram, located in the North West Frontier
      Province of Pakistan after the October 2005 earthquake. Researchers arrived in
      the affected area during the second week after the earthquake, and remained there
      for one week. During this period, patients were received from distant areas of
      the district. These patients were admitted to a tent hospital because the
      district headquarters hospital was completely damaged. Those requiring orthopedic
      surgical intervention or closed manipulation and plaster of paris casts were
      included in the study. RESULTS: Of 110 patients, 61 were female and 49 were male,
      and 140 bones were involved. In this series, 92 fractures were closed, while 48
      were open. A total of 67.3% of the patients were <40 years of age. The tibia was
      involved in 32.1% of cases and the femur 16.4%. No cases of compartment syndrome
      were found. Wound debridement was performed in 35 cases. An external fixator was
      applied to 10 cases of open tibia fractures. Four humerus fractures and a
      fracture to the radius and ulna were fixed with the Rashnail method. One open
      femur fracture was repaired with external fixation. Pre- and post-operative
      antibiotics were administered in all cases. Thirty patients sustained injuries in
      addition to orthopedic trauma: 13 vertebral injuries, eight head injuries, six
      fractured ribs, three blunt injuries to the abdomen, and 10 significant soft
      tissues injuries without bony involvement. CONCLUSIONS: After the earthquake in
      Battagram, young persons, especially females, were prone to orthopedic injuries,
      mainly involving the extremities. A comprehensive disaster plan would have helped
      to manage these emergencies, and further experience is needed for on-site
      surgical interventions.

PMID- 22985735
TI  - Comparative cytological responses of lung epithelial and pleural mesothelial
      cells following in vitro exposure to nanoscale SiO2.
AB  - Due to unique surface chemistries and the ability to easily functionalize their
      surface, amorphous silica nanoparticles are being assimilated into medicinal and
      consumer products at an increasing rate. Subsequently, there is an emergent need
      to understand the interactions of these particulates with biological systems in
      an attempt to mitigate toxicity. The identification of susceptible or resistant
      cell types of the pulmonary system remains a critical step in the development of
      toxicity assessments for nanoparticle-based platforms. Specific to this study,
      the cellular responses of A549 lung epithelial and MeT-5A pleural mesothelial
      cell lines as a means of detecting nanoparticle-induced oxidative stress were
      examined. Basal expression and cellular antioxidant activity, including SOD, CAT,
      and GSH, were examined prior to H(2)O(2) and ~30 nm SiO(2) (0.01-100mg/L)
      exposures. Dose-response observations were made regarding oxidant production,
      cytotoxicity, GSH depletion and NRF2 transcription factor activation. Results
      indicated that, while both cell types exhibited susceptibility to H(2)O(2) and
      SiO(2)-induced oxidative stress and damage, the A549 cell line was relatively
      more resilient.

PMID- 22985737
TI  - Self-ratings of higher olfactory acuity contrast with reduced olfactory test
      results of fibromyalgia patients.
AB  - BACKGROUND: Self-reports of fibromyalgia (FM) patients about an enhanced
      olfactory acuity have been used to characterize them as persons with a general
      increased sensitivity to sensory input consistent with a central sensitization.
      However, as reduced activations in some brain areas also seem to accompany FM, a
      multisensory hypersensitivity is not a necessary consequence. METHODS: FM
      patients meeting ARA (American Rheumatism Association) criteria (16 women and one
      man, aged 23-56 years, spontaneous pain 32-91 mm visual analog scale [VAS], 14-18
      tender points with a pressure pain threshold of 1.5+/-0.7 kg/cm(2)) received an
      olfactory test (Sniffn' Sticks) to assess their odor thresholds to n-butanol and
      their ability to discriminate and identify odors. Healthy controls were 14 age
      matched women and one man. RESULTS: Patients had poorer odor identification than
      controls (14.6+/-1.3 vs. 15.5+/-0.6; p<0.05) but did not differ in odor
      thresholds or odor discrimination. This test result contrasted with the patients'
      self-ratings of their olfactory sensitivity as higher than average. CONCLUSIONS:
      The perception of FM patients as being multisensory hypersensitive is not
      supported by present results. In contrast to the subjects' self-ratings,
      measurements of olfactory function showed a slightly reduced odor identification,
      with a by-and-large normal performance.

PMID- 22985736
TI  - Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of
      rat calvarial osteoblasts--in vitro.
AB  - Di-2-ethyl hexyl phthalate (DEHP), an industrial plasticizer and a ubiquitous
      environmental contaminant, is an established endocrine disruptor (ED). Increasing
      evidences indicate that some EDs interfere with osteoblast differentiation and
      function. In the present study, we investigated the effects of DEHP on the
      expression of cell cycle proteins, differentiation markers, Runx2 and its co
      activator TAZ in osteoblasts derived from neonatal rat calvaria. A significant
      decrease in protein levels of cyclin D1 and CDK-2 was found at high dosage of
      DEHP (100 MUM) after 24h treatment. DEHP treatment caused a significant decrease
      in ALP mRNA. While DEHP treatment significantly decreased the TAZ at mRNA and
      protein levels, it decreased only the Runx2protein levels. Histochemical
      localization of ALP, collagen and mineralized nodules studied from cells treated
      with DEHP (10 and 100 MUM) for 21 days revealed a drastic decrease in collagen,
      ALP and mineralization. In conclusion, DEHP affected differentiation of neonatal
      rat calvarial osteoblasts and mineralization of matrix secreted by these cells.

PMID- 22985738
TI  - EEG correlates of spontaneous self-referential thoughts: a cross-cultural study.
AB  - The default mode network (DMN) has been mostly investigated using positron
      emission tomography and functional magnetic resonance imaging (fMRI) and has
      received mixed support in electroencephalographic (EEG) studies. In this study,
      after sLORETA transformation of EEG data, we applied group spatial independent
      component analysis which is routinely used in fMRI research. In three large and
      diverse samples coming from two different cultures (Russian and Taiwanese),
      spontaneous EEG data and retrospective questionnaire measures of subject's state,
      thoughts, and feelings during the EEG registration were collected. Regression
      analyses showed that appearance of spontaneous self-referential thoughts was best
      predicted by enhanced alpha activity within the DMN. Diminished theta and delta
      activity in the superior frontal gyrus and enhanced beta activity in the
      postcentral gyrus added to the prediction. The enhanced alpha activity prevailed
      in the posterior DMN hub in Russian, but in the anterior DMN hub in Taiwanese
      participants. Possible cross-cultural differences in personality and attitudes
      underlying this difference are discussed.

PMID- 22985739
TI  - Environmental exposure to arsenic and cadmium during pregnancy and fetal size: a
      longitudinal study in rural Bangladesh.
AB  - Prenatal exposures to arsenic (As) and cadmium (Cd) have been associated with
      decreased size at birth. We here studied associations of prenatal As and Cd
      exposures with multiple fetal size parameters measured by ultrasound in
      gestational week (GW) 14 and 30 in a population-based mother-child cohort in
      rural Bangladesh. We measured As (n=1929) and Cd (n=1616) in urine during
      pregnancy. In the longitudinal evaluation of combined exposure, urinary Cd (UCd)
      showed an inverted U-shaped association (turning-point 1.5 MUg Cd/L) with all
      fetal size parameters, while UAs showed no significant association. Cross
      sectional analyses indicated that associations with UCd were somewhat stronger in
      early gestation. Stratification indicated stronger associations between UCd and
      fetal size in girls than in boys, and in poorer than in richer families, while
      UAs was weakly associated with fetal size in boys. In conclusion, particularly
      Cd, but also As, appeared to influence fetal development in a sex-dependent
      manner.

PMID- 22985740
TI  - Porous ceramic titanium dioxide scaffolds promote bone formation in rabbit peri
      implant cortical defect model.
AB  - Titanium oxide (TiO2) scaffolds have previously been reported to exhibit very low
      mechanical strength. However, we have been able to produce a scaffold that
      features a high interconnectivity, a porosity of 91% and a compressive strength
      above 1.2 MPa. This study analyzed the in vivo performance of the porous TiO2
      scaffolds in a peri-implant cortical defect model in the rabbit. After 8 weeks of
      healing, morphological microcomputed tomography analyses of the defects treated
      with the TiO2 scaffolds had significantly higher bone volume, bone surface and
      bone surface-to-volume ratio when compared to sham, both in the cortical and bone
      marrow compartment. No adverse effects, i.e. tissue necrosis or inflammation as
      measured by lactate dehydrogenase activity and real-time reverse transcription
      polymerase chain reaction analysis, were observed. Moreover, the scaffold did not
      hinder bone growth onto the adjacent cortical titanium implant. Histology clearly
      demonstrated new bone formation in the cortical sections of the defects and the
      presence of newly formed bone in close proximity to the scaffold surface and the
      surface of the adjacent Ti implant. Bone-to-material contact between the newly
      formed bone and the scaffold was observed in the histological sections. Islets of
      new bone were also present in the marrow compartment albeit in small amounts. In
      conclusion, the present investigation demonstrates that TiO2 scaffolds
      osseointegrate well and are a suitable scaffold for peri-implant bone healing and
      growth.

PMID- 22985741
TI  - Effects of enamel matrix proteins on multi-lineage differentiation of periodontal
      ligament cells in vitro.
AB  - The adult periodontal ligament (PDL) is considered to contain progenitor cells
      that are involved in the healing of periodontal wounds. Treatment with enamel
      matrix derivative (EMD), a heat-treated preparation derived from enamel matrix
      proteins (EMPs), has been shown to be of some clinical benefit in eliciting
      periodontal regeneration in vivo. Although there is extensive information
      available about the effects of EMD on periodontal regeneration, the precise
      influence of this material on alveolar bone and the formation of blood vessels
      and proprioceptive sensory nerves, prominent features of functionally active
      periodontal tissue, remain unclear. The aim of the present study was therefore to
      examine the effects of EMD on the ability of human periodontal ligament cells
      (HPCs) to undergo multi-lineage differentiation in vitro. Our results showed that
      HPCs treated with EMD under non-selective growth conditions did not show any
      evidence of osteogenic, adipogenic, chondrogenic, neovasculogenic, neurogenic and
      gliogenic "terminal" differentiation. In contrast, under selective lineage
      specific culture conditions, EMD up-regulated osteogenic, chondrogenic and
      neovasculogenic genes and "terminal" differentiation, but suppressed
      adipogenesis, neurogenesis and gliogenesis. These findings thus demonstrate for
      the first time that EMD can differentially modulate the multi-lineage
      differentiation of HPCs in vitro.

PMID- 22985742
TI  - Gender- and age-related differences in clinical presentation and management of
      outpatients with stable coronary artery disease.
AB  - INTRODUCTION: Contemporary generalizable data on the demographics and management
      of outpatients with stable coronary artery disease (CAD) in routine clinical
      practice are sparse. Using the data from the CLARIFY registry we describe gender-
      and age-related differences in baseline characteristics and management of these
      patients across broad geographic regions. METHODS: This international,
      prospective, observational, longitudinal registry enrolled stable CAD outpatients
      from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North,
      Central, and South America. RESULTS: Baseline data were available for 33280
      patients. Mean (SD) age was 64 (10.5) years and 22.5% of patients were female.
      The prevalence of CAD risk factors was generally higher in women than in men.
      Women were older (66.6 vs 63.4 years), more frequently diagnosed with diabetes
      (33% vs 28%), hypertension (79% vs 69%), and higher resting heart rate (69 vs 67
      bpm), and were less physically active. Smoking and a history of myocardial
      infarction were more common in men. Women were more likely to have angina (28% vs
      20%), but less likely to have undergone revascularization procedures. CAD was
      more likely to be asymptomatic in older patients perhaps because of reduced
      levels of physical activity. Prescription of evidence-based medication for
      secondary prevention varied with age, with patients >= 75 years treated less
      often with beta blockers, aspirin and angiotensin-converting enzyme inhibitors
      than patients <65 years. CONCLUSIONS: Important gender-related differences in
      clinical characteristics and management continue to exist in all age groups of
      outpatients with stable CAD.

PMID- 22985743
TI  - Evaluation by MRA of aortic dilation late after repair of tetralogy of Fallot.
AB  - OBJECTIVES: This study evaluated predictors for aortic dilation (AD) in patients
      with repaired tetralogy of Fallot (rTOF) using magnetic resonance angiography
      (MRA). BACKGROUND: AD is common in patients with rTOF and may result in increased
      morbidity and mortality. There are no guidelines for evaluation of AD for rTOF
      patients. METHODS: All adults with rTOF who previously underwent MRA had
      retrospective aortic measurements at the sinuses of Valsalva (SoV) and ascending
      aorta (AsAo). Rate of change in diameter was determined in patients with multiple
      MRAs. Chart review identified risk factors for AD. Univariate and multivariate
      analyses tested predictors of AD. RESULTS: Of the 87 patients who met the
      inclusion criteria, 12 (14%) had AD. At baseline, mean diameter was 3.6 +/- 0.6
      cm and 3.1 +/- 0.6 cm at the SoV and AsAo, respectively. The AsAo was larger than
      the SoV in 17%. Predictors of AD included male gender, age, right aortic arch,
      pregnancy, older age at complete repair, smoking, and systemic hypertension.
      Serial studies were available in 55 patients; the rate of growth was slow: 0.4 +/
      0.9 mm/year (SoV) and 0.1 +/- 0.8mm/year (AsAo). CONCLUSIONS: AD is common in
      rTOF at the SoV and AsAo. Transthoracic echocardiography, which does not always
      image the AsAo as well as MRA, may not image AD in rTOF in cases in which the
      AsAo is dilated. Although several risk factors correlate with AD in rTOF, the
      rate of aortic growth is slow, suggesting that rTOF patients may not require
      frequent aortic imaging.

PMID- 22985745
TI  - EAU guidelines on assessment and nonsurgical management of urinary incontinence.
AB  - CONTEXT: The previous European Association of Urology (EAU) guidelines on urinary
      incontinence comprised a summary of sections of the 2009 International
      Consultation on Incontinence. A decision was made in 2010 to rewrite these
      guidelines based on an independent systematic review carried out by the EAU
      guidelines panel, using a sustainable methodology. OBJECTIVE: We present a short
      version of the full guidelines on assessment, diagnosis, and nonsurgical
      treatment of urinary incontinence, with the aim of increasing their
      dissemination. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic
      review of existing systematic reviews and independent new literature searches,
      based on Population, Intervention, Comparator, Outcome questions. Appraisal of
      papers was carried out by an international panel of experts, who also
      collaborated on a series of consensus discussions, to develop concise structured
      evidence summaries and action-based recommendations using a modified Oxford
      system. EVIDENCE SUMMARY: The full version of the guidelines is available online
      (http://www.uroweb.org/guidelines/online-guidelines/). The guidelines include
      algorithms that refer the reader back to the supporting evidence, and they are
      more immediately useable in daily clinical practice. CONCLUSIONS: These new
      guidelines present an up-to-date summary of the available evidence, together with
      clear clinical algorithms and action-based recommendations based on the best
      available evidence. Where such evidence does not exist, they present a consensus
      of expert opinion.

PMID- 22985744
TI  - Probability and predictors of remission from life-time prescription drug use
      disorders: results from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - While prescription drug use disorders (PDUD) has become an important and growing
      public health problem, little is known about their course. This study aims to
      estimate cumulative probability of remission from sedatives, tranquilizers,
      opioids and stimulants, and to identify predictors of remission across
      substances. Analyses were done for the sub-sample of individuals with lifetime
      history of abuse or dependence on sedatives (n = 402), tranquilizers (n = 372),
      opioids (n = 521), and stimulants (n = 765) at Wave 1 of the National
      Epidemiological Survey on Alcohol and Related Conditions (NESARC). Cumulative
      probability estimates and hazard ratios for remission from PDUD were obtained for
      the general population. Lifetime cumulative probability estimates of remission
      were above 96% for all substances assessed. Half of the cases of PDUD remitted
      between 4 and 5 years after onset. Remission from PDUD was greater for younger
      individuals. Males exhibited lower hazards of remission for stimulants use
      disorder. A diagnosis of personality disorders decreased probability of remission
      for sedatives and stimulants. Only abuse or dependence on some prescription drugs
      decreased the probability of remission from other PDUD, whereas other drug
      disorders did not predict remission. A significant proportion of individuals with
      PDUD achieve remission at some point in their life-time. Predictors of remission
      were found to be mostly substance-specific rather than common across substances.
      The lower rates of remission among some subgroups of the population highlight the
      need to strengthen preventive and intervention efforts among vulnerable
      population subgroups.

PMID- 22985746
TI  - Comparative outcomes of primary, recurrent, and progressive high-risk non-muscle
      invasive bladder cancer.
AB  - BACKGROUND: The treatment of high-risk non-muscle-invasive bladder cancer (BCa)
      is problematic given the variable natural history of the disease. Few reports
      have compared outcomes for primary high-risk tumours with those that develop
      following previous BCas (relapses). The latter represent a self-selected cohort,
      having failed previous treatments. OBJECTIVE: To compare outcomes in patients
      with primary, progressive, and recurrent high-risk non-muscle-invasive BCa.
      DESIGN, SETTING, AND PARTICIPANTS: We identified all patients with primary and
      relapsing high-risk BCa tumours at our institution since 1994. Relapses were
      divided into progressive (previous low- or intermediate-risk disease) and
      recurrent (previous high-risk disease) cancers. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Relationships with outcome analysed using multivariable Cox
      regression and log-rank analysis. RESULTS AND LIMITATIONS: We identified 699
      primary, 110 progressive, and 494 recurrent high-risk BCa tumours in 809 patients
      (average follow-up: 59 mo [interquartile range: 6-190]). Muscle invasion occurred
      most commonly in recurrent (23%) tumours, when compared to progressive (20%) and
      primary (14.6%) cohorts (log rank p<0.001). Disease-specific mortality (DSM)
      occurred more frequently in patients with recurrent (25.5%) and progressive
      (24.6%) tumours compared to primary disease (19.2%; log rank p=0.006). Other
      cause mortality was similar in all groups (log rank p=0.57), and overall
      mortality was highest in the progressive cohort (62%) compared with the recurrent
      (58%) and primary groups (54%; log rank p<0.001). In multivariable analysis,
      progression and DSM were predicted by tumour grouping (hazard ratio [HR]: >1.15;
      p<0.026), stage (HR: >1.30; p<0.001), and patient age and sex (HR: >1.03;
      p<0.037). Carcinoma in situ was only predictive of outcome in primary tumors.
      Limitations include retrospective design and limited details regarding bacillus
      Camille-Guerin use. CONCLUSIONS: Patients with relapsing, high-risk, BCa tumors
      have higher progression, DSM, and overall mortality rates than those with primary
      cancers. The use of bladder-sparing strategies in these patients should
      approached cautiously. Carcinoma in situ has little predicative role in
      relapsing, high-risk, BCa tumors.

PMID- 22985747
TI  - The natural flavonoid galangin inhibits osteoclastic bone destruction and
      osteoclastogenesis by suppressing NF-kappaB in collagen-induced arthritis and
      bone marrow-derived macrophages.
AB  - We investigated the effect of galangin, a natural flavonoid, on osteoclastic bone
      destruction in collagen-induced arthritis and examined the molecular mechanisms
      by which galangin affects osteoclastogenesis in bone marrow derived macrophages.
      In mice with collagen-induced arthritis, administration of galangin significantly
      reduced the arthritis clinical score, edema and severity of disease without
      toxicity. Interestingly, galangin treatment during a later stage of collagen
      induced arthritis, using mice with a higher clinical arthritis score, still
      significantly slowed the progression of the disease. Extensive cartilage and bone
      erosive changes as well as synovial inflammation, synovial hyperplasia and pannus
      formation were dramatically inhibited in arthritic mice treated with galangin.
      Furthermore, galangin-treated arthritic mice showed a significant reduction in
      the concentrations of IL-1beta, TNF-alpha and IL-17. We found that galangin
      inhibited osteoclastogenic factors and osteoclast formation in bone marrow
      derived macrophages and osteoblast co-cultured cells, and increased
      osteoprotegerin (OPG) levels in osteoblasts. Galangin and NF-kappaB siRNA
      suppressed RANKL-induced phosphorylation of the c-jun N-terminal kinase (JNK) and
      p38 mitogen-activated protein kinase (MAPK), but not AKT and extracellular signal
      regulated kinase 1/2 (ERK1/2). Also, the JNK inhibitor SP600125 and p38 inhibitor
      SB203580 reduced RANKL-induced expressions of phospho-c-Jun, c-fos and NFATc1
      genes during osteoclast development. In addition, galangin suppressed RANKL
      induced phosphorylation of NF-kappaB, phospho-IkappaBalpha, inflammatory
      cytokines and osteoclast formation in bone marrow-derived macrophages. Our data
      suggest that galangin prevented osteoclastic bone destruction and
      osteoclastogenesis in osteoclast precursors as well as in collagen-induced
      arthritis mice without toxicity via attenuation of RANKL-induced activation of
      JNK, p38 and NF-kappaB pathways.

PMID- 22985748
TI  - Towards a structural understanding of PARP1 activation and related signalling ADP
      ribosyl-transferases.
AB  - ADP-ribosylation is a post-translational modification of proteins that occurs
      mostly in response to cellular stress and is catalysed by members of the diverse
      poly-ADP-ribose (PAR) polymerase (PARP/ARTD) family. The founding member of the
      family, PARP1, is best recognized for its function as a sensor of DNA strand
      lesions, but ADP-ribosylation has been implicated in transcriptional regulation,
      chromatin dynamics, telomere maintenance, apoptosis and neuronal signalling. Here
      we summarize a number of exciting recent breakthroughs in our understanding of
      the structural and mechanistic aspects of how PARP1 recognizes DNA, how PARPs are
      regulated, how ADP-ribose modifications are set onto specific targets and how the
      cellular machinery recognizes this elusive post-translational modification.

PMID- 22985749
TI  - The role of CT and staging laparoscopy in the staging of gastric cancer.
AB  - AIM: To assess the relative roles of computed tomography (CT) and diagnostic
      laparoscopy in the staging process of patients with potentially curable gastric
      cancer. MATERIALS AND METHODS: Fifty-two patients underwent laparoscopy and CT as
      part of staging; 36 patients underwent surgery without laparoscopy. Pathological
      findings at laparoscopy or surgery were compared with initial CT reports, and
      analysis of the sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) was performed. RESULTS: Of the patients who
      underwent laparoscopy and CT, six were staged as positive for peritoneal disease
      (PD), of which five (83%) were positive for PD at laparoscopy. Forty-six patients
      were reported at CT as negative for PD, of which 40 (87%) were negative at
      laparoscopy. Of 36 patients with no advanced disease at CT, who had surgery
      without diagnostic laparoscopy, nine (25%) were positive at surgery for PD. The
      overall sensitivity of CT for PD was therefore 25%, the specificity was 99%, the
      PPV was 86%, and the NPV was 83%. CONCLUSION: CT is not sufficiently sensitive to
      detect or exclude PD in patients with gastric cancer, although is highly
      specific. Staging laparoscopy is an essential adjunct to imaging in all patients
      being considered for curative surgery for gastric cancer.

PMID- 22985750
TI  - Multimodality imaging of the Essure tubal occlusion device.
AB  - The Essure device is a permanent birth-control device, which is gaining
      popularity. The micro-inserts are composed of metallic elements that can be seen
      on radiography, computed tomography, ultrasound, and magnetic resonance imaging.
      Knowledge of the normal location and appearance of the Essure device will ensure
      appropriate patient care. The purpose of this review is to describe the Essure
      tubal occlusion device and illustrate its normal and abnormal appearance using
      various imaging methods.

PMID- 22985753
TI  - [Analysis of the training and teaching situation of anaesthesiology and
      resuscitation tutors in Spain: a proposal for improvement].
AB  - OBJECTIVES: To determine the current situation of the tutors in our specialty as
      regards resident/tutor ratios, times they have available to develop their work,
      the training that they have received to perform their function, and whether this
      is recognised by official bodies, other than by their own hospital. Furthermore,
      to determine the teaching and research work taught to the residents through the
      sessions, as well as their participation in publications per year. To find out
      their opinion of the tutors as regards unifying training contents, whether or not
      they have objective tests on finishing their residency, and their willingness to
      take part in the project promoted by the Teaching Section of SEDAR to carry out a
      common minimum theoretical-practical programme throughout the whole of Spain.
      MATERIAL AND METHODS: A questionnaire with the aforementioned questions was sent
      to Anaesthesiology Teach Units through the different regional coordinators,
      during the years 2008-2010. RESULTS: A total of 77/106 (72.6%) Teaching Units
      responded. The mean ratio of residents per tutor was 5.6+/-3.3. More than 60% of
      the tutors had not attended any training course or even how to join one in the
      two years of the study; 62.3% did not have specific time available to develop
      their role as tutors, and in 18.2%, their work was only recognised by health
      institutions. The number of teaching sessions for residents per year was 5.0+/
      4.0 and the number of publications was 1.6+/-1.4. Almost all of them (98.7%)
      believe it was necessary to produce a programme that would ensure similar minimum
      theoretical-practical training plans and that on their own initiative had been
      carried out in 70% of Teaching Units, but without uniform criteria. Almost three
      quarters (74%) had not presented any resident to the European Examination of
      Anaesthesia in the last few years, and 87% considered the system of evaluating
      residents as inadequate, with 79% in favour of having a final exam or test.
      CONCLUSIONS: The tutor/resident ratio should according to that stipulated. Time
      needs to be set aside for teaching, separate from care work, and our tutors, in
      general, lack specific training courses, and these are very disparate. There is a
      general demand to have a training programme of common minimum theoretical
      practical skills. It is considered that the current evaluation system is
      inadequate, but there is no unanimity in whether or not to have an exam at the
      end of the residency, although the European Examination could be the model to
      consider in this regard.

PMID- 22985752
TI  - [Questionnaire on the anaesthesiology treatment of patients subjected to
      posterior fossa neurosurgery].
AB  - OBJECTIVES: To find out, by means of a questionnaire, the procedures used by
      Spanish anaesthetists in peri-operative management of patients subjected to
      neurosurgery of the posterior cranial fossa. MATERIAL AND METHODS: A closed
      question type questionnaire was sent to Anaesthesiology Departments with a
      Neurosurgery Department on the participation of anaesthetists in the peri
      operative treatment of patients subjected posterior fossa surgery. RESULTS: The
      questionnaire was completed by 42 (57.5%) of the 73 national public hospitals
      with a Neurosurgery Department. The posterior fossa surgery was performed in the
      sitting position in 36 hospitals, although it was less frequently used than the
      lateral decubitus or prone decubitus position. There was little specific
      neurological monitoring, as well as little use of precordial and/or transcranial
      Doppler for detecting vascular air embolism. Nitrous oxide was used in less than
      10% of the centres, and 15% avoided neuromuscular block when neurophysiological
      monitoring was used during the surgery. Cardiovascular problems were mentioned as
      being the most frequent in 29% of the centres, while in the post-operative period
      the most common complications were, cranial nerve deficit, airway oedema (23%),
      and post-operative vomiting (47%). CONCLUSIONS: The results obtained from the
      questionnaire showed that the sitting position was less used than the prone
      position in posterior fossa surgery, and that neurophysiological monitoring is
      during surgery is hardly used.

PMID- 22985755
TI  - [Effect of nebulised iloprost combined with inhaled nitric oxide and oral
      sildenafil on lung transplant patients. Therapeutic efficacy in pulmonary
      hypertension during surgery].
AB  - OBJECTIVES: There is a high incidence of pulmonary hypertension during the lung
      transplant peri-operative period, and could lead to a haemodynamic deterioration
      that may require the need of extracorporeal circulation. Our aim was to study the
      haemodynamic effects on the pulmonary and systemic circulation of the combination
      of inhaled nitric oxide and iloprost and oral sildenafil in patients with severe
      pulmonary hypertension during lung transplant surgery. PATIENTS AND METHODS:
      Seventeen patients received 10MUg of nebulised iloprost during the peri-operative
      period of the lung transplant when their mean pulmonary pressure exceeded 50mmHg.
      AU the patients received 50mg of oral sildenafil 30min before anaesthetic
      induction, 20ppm of inhaled nitric oxide after tracheal intubation. The
      haemodynamic and respiratory variables were recorded at baseline (after
      anaesthetic induction), prior to the administering of iloprost, and at 5 and
      30min after it was given. RESULTS: The administering of iloprost significantly
      reduced the pulmonary arterial pressure and significantly increases the cardiac
      Index and the right ventricular ejection fraction. There were no significant
      changes occurred in the systemic arterial pressure. CONCLUSIONS: The triple
      combination significantly reduces the pulmonary pressures in the lung transplant
      peri-operative and should be considered when there is severe pulmonary
      hypertension during the surgery or during the immediate post-operative period of
      lung transplantation.

PMID- 22985754
TI  - [The objective structured clinical evaluation of teaching in anaesthesiology and
      resuscitation].
AB  - OBJECTIVES: To find out the acquirement of professional competencies of
      Anaesthesiology and Resuscitation medical residents at the end of their training
      period using the Objective Structured Clinical Evaluation (OCSE) tool. MATERIAL
      AND METHODS: Six competency components to evaluate were defined as follows:
      clinical interview (communication), technical ability and relationship abilities
      (leadership, decision making, work in a team), diagnostic assessment, therapeutic
      management, and medical records. Different methodologies were determined
      depending on the knowledge and skills to evaluate. Twelve clinical cases were
      developed that were performed in 12 stations. A total of 107 Items, specified
      within the stations, evaluated the competency components. A total of 43 residents
      were invited to participate in the last 4 months of their training in hospitals
      in Andalusia and Extremadura. RESULTS: A total of 33 residents participated. The
      overall mean of the classifications obtained in the 12 stations was 64.2 out of a
      maximum of 100. The medical residents demonstrated higher competency in
      obstetrics, paediatric anaesthesia, and that associated with difficult airway.
      The main competency gaps were detected in the area of one-day surgery, chronic
      pain, and literature management, in which approximately half passed the test.
      CONCLUSIONS: We believe that training evaluations, such as the OCSE, help in
      determining the skill levels of the medical resident, making it easier to
      continually improve the training of the future anaesthesiologist.

PMID- 22985756
TI  - [Indications and use of prothrombin complex in cardiac surgery].
AB  - On of the most common, and serious, complications in cardiac surgery is
      postoperative bleeding. According to the majority of studies, between 10% and 92%
      of patients subjected to elective surgery require transfusions of blood products
      and blood derivatives. Transfusions and reinterventions are associated with
      longer stays in critical care units and a decrease in survival rates. There have
      been some important changes in the treatment of changes in haemostasis and post
      surgical bleeding in the last few years, particularly with the introduction into
      clinical practice of working procedures backed up by clinical guidelines, as well
      as the appearance of new drugs. The aim of this work is to describe the main
      characteristics and update the use of prothrombin complexes that are currently
      available in Spain, with special emphasis on their use in cardiac surgery.

PMID- 22985757
TI  - [Postoperative cortical blindness after right upper lung lobectomy].
AB  - Changes in vision after non-ophthalmic surgery are a serious complication that
      can have devastating consequences due to its potential irreversibility. This not
      only leads to medical problems, but also legal ones. Many causes that affect
      sight during the peri-operative period have been identified, whether due to optic
      nerve damage or of extra-ocular origin (in the neuro-optic pathways and/or
      cerebral cortex). AU these may have a multifactorial origin, and there is still
      controversy as regards it pathogenesis and treatment. We present the case of a
      thoracic surgery patient who had a bilateral amaurosis in the post-operative
      period, which had a favourable outcome.

PMID- 22985759
TI  - [AIRTRAQ as the device of choice for infants with known difficult airway].

PMID- 22985760
TI  - [Doubts and difficulties observed on following the "recommendations for the
      prevention and treatment of postoperative nausea and vomiting associated with
      opioid infusions"].

PMID- 22985758
TI  - [Postoperative assessment of cognitive state: a preliminary comparative study of
      lumbar plexus or epidural analgesia in patients subjected to hip-replacement
      surgery].

PMID- 22985761
TI  - [Response to comments on the article "recommendations for the prevention and
      treatment of postoperative nausea and vomiting associated with opioid
      infusions"].

PMID- 22985762
TI  - [Anaesthesia in a patient with Lesch-Nyhan syndrome].

PMID- 22985763
TI  - [Presentation of a case of Paraquat poisoning].

PMID- 22985764
TI  - [Post-tracheal intubation rupture treated with a Dumon-Y stent].

PMID- 22985765
TI  - [Paramedian puncture for subarachnoid anaesthesia in a patient with a large
      tattoo].

PMID- 22985766
TI  - Control of the temperature rise in magnetic hyperthermia with use of an external
      static magnetic field.
AB  - Our purpose in this study was to investigate the usefulness of a method for
      controlling the temperature rise in magnetic hyperthermia (MH) using an external
      static magnetic field (SMF), and to derive an empirical equation for describing
      the energy dissipation of magnetic nanoparticles (MNPs) in the presence of both
      the alternating magnetic field (AMF) and SMF through phantom experiments. We made
      a device that allows for MH in the presence of an SMF with a field-free point
      (FFP) using a Maxwell coil pair. We measured the temperature rise of MNPs under
      various conditions of AMF and SMF and various distances from the FFP (d), and
      calculated the specific absorption rate (SAR) from the initial slope of the
      temperature curve. The SAR values decreased with increasing strength of SMF (Hs)
      and d. The extent of their decrease with d increased with an increase of the
      gradient of SMF (Gs). The relationships between SAR and Hs and between SAR and d
      could be well approximated by Rosensweig's equation in which the amplitude of AMF
      (Hac) is replaced by ?[Hac(2)]/?[Hac(2)+Hs(2)], except for the case when Gs was
      small. In conclusion, the use of an external SMF with an FFP will be effective
      for controlling the temperature rise in MH in order to reduce the risk of heating
      surrounding healthy tissues, and our empirical equation will be useful for
      estimating SAR in the presence of both the AMF and SMF and for designing an
      effective local heating system for MH.

PMID- 22985768
TI  - The effect of the AED and AED programs on survival of individuals, groups and
      populations.
AB  - OBJECTIVE: The automated external defibrillator (AED) is a tool that contributes
      to survival with mixed outcomes. This review assesses the effectiveness of the
      AED, consistencies and variations among studies, and how varying outcomes can be
      resolved. METHODS: A worksheet for the International Liaison Committee on
      Resuscitation (ILCOR) 2010 science review focused on hospital survival in AED
      programs was the foundation of the articles reviewed. Articles identified in the
      search covering a broader range of topics were added. All articles were read by
      at least two authors; consensus discussions resolved differences. RESULTS: AED
      use developed sequentially. Use of AEDs by emergency medical technicians (EMTs)
      compared to manual defibrillators showed equal or superior survival. AED use was
      extended to trained responders likely to be near victims, such as fire/rescue,
      police, airline attendants, and casino security guards, with improvement in all
      venues but not all programs. Broad public access initiatives demonstrated
      increased survival despite low rates of AED use. Home AED programs have not
      improved survival; in-hospital trials have had mixed results. Successful programs
      have placed devices in high-risk sites, maintained the AEDs, recruited a team
      with a duty to respond, and conducted ongoing assessment of the program.
      CONCLUSION: The AED can affect survival among patients with sudden ventricular
      fibrillation (VF). Components of AED programs that affect outcome include the
      operator, location, the emergency response system, ongoing maintenance and
      evaluation. Comparing outcomes is complicated by variations in definitions of
      populations and variables. The effect of AEDs on individuals can be dramatic, but
      the effect on populations is limited.

PMID- 22985769
TI  - A highly-sulfated chondroitin sulfate, CS-E, adsorbs specifically to neurons with
      nuclear condensation.
AB  - A highly sulfated chondroitin sulfate, CS-E, prevents excitatory amino acid
      induced neuronal cell death by an as yet unknown mechanism. To reveal this
      mechanism, we pretreated neurons in culture with various inhibitors, and examined
      whether N-methyl-D-aspartic acid (NMDA)-induced neuronal cell death was reduced
      in the presence of CS-E. The inhibitors of protein kinase C (PKC) and
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) ameliorated NMDA-induced
      neuronal cell death, but did not affect the neuroprotective activity of CS-E.
      Among the growth factors with which CS-E can interact, high concentration of BDNF
      protected against the NMDA-induced neuronal cell death and strengthened
      neuroprotection by CS-E. CS-E, but neither CS-A nor CS-C, adsorbed to a subclass
      of neurons with nuclear condensation, namely pyknosis. Contactin-1 (CNTN-1), a
      putative receptor for neuritogenic activity of CS-E, was present in cortical
      neurons, but a neutralizing antibody to CNTN-1 did not block neuroprotective
      activity of CS-E. The results suggest that CS-E may prevent the progression of
      cell death at the early stages of excitotoxicity through a signaling pathway
      different from CNTN-1.

PMID- 22985770
TI  - Characterization of strain rate sensitivity in pharmaceutical materials using
      indentation creep analysis.
AB  - Understanding how a material's response to stress changes as the stress is
      applied at different rates is important in predicting performance of
      pharmaceutical powders during tablet compression. Widely used methods for
      determining strain rate sensitivity (SRS) are empirically based and can often
      provide inconsistent or misleading results. Indentation creep data, collected
      during hardness tests on compacts formed from several common tableting
      excipients, were used to predict each material's relative sensitivity to changes
      in strain rate. Linear relationships between Ln(indentation hardness) and
      Ln(strain rate) were observed for all materials tested. The slope values taken
      from these relationships were compared to traditional strain rate sensitivity
      estimates based on in-die Heckel analysis. Overall, the results from the two
      methods were quite similar, but several advantages were evident in the creep
      data. The most notable advantage was the ability to characterize strain rate
      sensitivity derived from plastic behavior with little influence of elastic
      deformation. For example, two grades of corn starch had very similar creep
      behavior, but their yield pressures were affected very differently when the
      compaction rate was increased. This inconsistency was related to the difference
      in the viscoelastic recovery exhibited by these two materials. This new method
      promises to allow a better understanding of strain rate effects observed during
      tablet manufacturing.

PMID- 22985767
TI  - Neurogenesis, inflammation and behavior.
AB  - Before the 1990s it was widely believed that the adult brain was incapable of
      regenerating neurons. However, it is now established that new neurons are
      continuously produced in the dentate gyrus of the hippocampus and olfactory bulb
      throughout life. The functional significance of adult neurogenesis is still
      unclear, but it is widely believed that the new neurons contribute to learning
      and memory and/or maintenance of brain regions by replacing dead or dying cells.
      Many different factors are known to regulate adult neurogenesis including immune
      responses and signaling molecules released by immune cells in the brain. While
      immune activation (i.e., enlargement of microglia, release of cytokines) within
      the brain is commonly viewed as a harmful event, the impact of immune activation
      on neural function is highly dependent on the form of the immune response as
      microglia and other immune-reactive cells in the brain can support or disrupt
      neural processes depending on the phenotype and behavior of the cells. For
      instance, microglia that express an inflammatory phenotype generally reduce cell
      proliferation, survival and function of new neurons whereas microglia displaying
      an alternative protective phenotype support adult neurogenesis. The present
      review summarizes current understanding of the role of new neurons in cognition
      and behavior, with an emphasis on the immune system's ability to influence adult
      hippocampal neurogenesis during both an inflammatory episode and in the healthy
      uninjured brain. It has been proposed that some of the cognitive deficits
      associated with inflammation may in part be related to inflammation-induced
      reductions in adult hippocampal neurogenesis. Elucidating how the immune system
      contributes to the regulation of adult neurogenesis will help in predicting the
      impact of immune activation on neural plasticity and potentially facilitate the
      discovery of treatments to preserve neurogenesis in conditions characterized by
      chronic inflammation.

PMID- 22985771
TI  - Real-time tablet formation monitoring with ultrasound measurements in eccentric
      single station tablet press.
AB  - A real-time ultrasound measurement system for tablet compression monitoring is
      introduced. The measurement system was tested in actual manufacturing environment
      and found to be capable of measuring the ultrasound response of the tabletting
      process from bulk to tablet. The tablet sets were compressed and the ultrasound
      measurements were conducted as implemented in eccentric single station tabletting
      apparatus in through transmission geometry. The speed of sound and ultrasound
      spectrum was measured during dynamic compression for microcrystalline
      cellulose/paracetamol tablets. The ultrasound system introduced in this study was
      found to be suitable for tabletting process monitoring as the mechanical
      properties of compressed tablets can be estimated during compression using the
      ultrasound system. In addition, it was found that the ultrasound was sensitive to
      the mixing time of magnesium stearate and the concentration of paracetamol. Thus,
      ultrasound measurements made during the compression can be used to monitor the
      tablet formation process.

PMID- 22985772
TI  - Assessment of disintegration of rapidly disintegrating tablets by a visiometric
      liquid jet-mediated disintegration apparatus.
AB  - The aim of this study was to develop a responsive disintegration test apparatus
      that is particularly suitable for rapidly disintegrating tablets (RDTs). The
      designed RDT disintegration apparatus consisted of disintegration compartment,
      stereomicroscope and high speed video camera. Computational fluid dynamics (CFD)
      was used to simulate 3 different designs of the compartment and to predict
      velocity and pressure patterns inside the compartment. The CFD preprocessor
      established the compartment models and the CFD solver determined the numerical
      solutions of the governing equations that described disintegration medium flow.
      Simulation was validated by good agreement between CFD and experimental results.
      Based on the results, the most suitable disintegration compartment was selected.
      Six types of commercial RDTs were used and disintegration times of these tablets
      were determined using the designed RDT disintegration apparatus and the USP
      disintegration apparatus. The results obtained using the designed apparatus
      correlated well to those obtained by the USP apparatus. Thus, the applied CFD
      approach had the potential to predict the fluid hydrodynamics for the design of
      optimal disintegration apparatus. The designed visiometric liquid jet-mediated
      disintegration apparatus for RDT provided efficient and precise determination of
      very short disintegration times of rapidly disintegrating dosage forms.

PMID- 22985773
TI  - Does neostigmine improve time to resolution of symptoms in acute colonic pseudo
      obstruction?
AB  - A best evidence topic was written according to a structured protocol. In
      [patients with acute colonic pseudo-obstruction] is [neostigmine] superior to
      [conservative treatment] with respect to [duration of symptoms and
      complications]. In total 51 papers were found using the reported search, and ten
      of these represented the best evidence to answer the clinical question. The
      authors, date, journal, study type, population, main outcome measures and results
      are tabulated. We conclude that intravenous neostigmine is associated with
      significantly reduced duration of acute colonic pseudo-obstruction (ACPO)
      compared to conservative treatment alone. Neostigmine infusion should be
      administered with continuous cardiac monitoring for possible bradycardia, which
      may require treatment with atropine. Seven prospective analyses and one
      retrospective study showed that intravenous neostigmine reduces time to
      resolution of clinical and radiological features of ACPO. One prospective study
      showed that neostigmine is only effective in improving duration of ACPO when it
      is combined with proponalol. One prospective study showed no difference in time
      to resolution of ACPO between neostigmine and conservative treatment but this
      study was limited by small sample size, lack of radiological examinations and
      poor reporting of adverse effects. In four separate studies patients experienced
      bradycardia with intravenous neostigmine and this required treatment with
      atropine. No other significant adverse effects were reported. Overall,
      intravenous neostigmine is associated with a significant reduction in duration of
      ACPO. In addition to regularly reviewing patients for antic-cholinergic side
      effects, patients should undergo continuous cardiac monitoring for bradycardia.
      The wide variety in methodology and measurement of outcomes reinforce the need
      for higher power studies to improve patient selection and monitoring of outcomes.

PMID- 22985774
TI  - Activation of NF-kappaB pathway in oral buccal mucosa during small intestinal
      ischemia-reperfusion injury.
AB  - BACKGROUND: Intestinal ischemia-reperfusion injury induces intestinal mucosal
      barrier disruption, systemic inflammatory response syndrome, multiorgan failure,
      and death. The major pathway for the systemic inflammatory responses depends on
      nuclear factor kappa B (NF-kappaB). However, direct measuring of NF-kappaB in
      injured tissues is not routinely available. Our aim was to determine whether NF
      kB pathway in buccal mucosa is activated during intestinal ischemia-reperfusion
      injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were prepared for the
      animal experiment. Superior mesenteric artery (SMA) was exposed and clamped for
      30 min in the intestinal ischemia-reperfusion (IR) group. SMA was exposed only in
      control group. Serum, buccal mucosa, and small intestinal mucosa were harvested
      in 90 min after reperfusion in IR or 120 min after SMA exposure in control group.
      Serum cytokine levels and tissue NF-kappaB pathway activities were measured.
      RESULTS: Serum TNF-alpha (5.49 +/- 2.72 versus 1.77 +/- 1.20 pg/mL, P = 0.002)
      and interleukin-6 (232.32 +/- 29.98 versus 115.92 +/- 17.81 pg/mL, P = 0.002)
      levels were significantly higher in IR than control group. Intestinal mucosal
      cytoplasmic phosphorylated inhibitor kappa B (IkappaB)/IkappaB ratio, nuclear NF
      kappaB expression, and NF-kappaB DNA-binding activity were significantly higher
      in IR than control group. Buccal mucosal cytoplasmic phosphorylated
      IkappaB/IkappaB ratio, nuclear NF-kappaB expression, and NF-kappaB DNA-binding
      activity were also higher in IR than control group. CONCLUSION: Buccal mucosal NF
      kappaB pathway was activated by intestinal ischemia-reperfusion injury. The
      present study suggests that buccal mucosal may be considered as an indicator for
      the assessment of intestinal ischemia-reperfusion injury.

PMID- 22985776
TI  - A randomized, controlled, multicenter study comparing intensity-modulated
      radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric
      cancer patients with D2 resection.
AB  - BACKGROUND AND PURPOSE: The role of postoperative chemoradiotherapy in the
      treatment of patients with gastric cancer with D2 lymph node curative dissection
      is not well established. In this study, we compared postoperative intensity
      modulated radiotherapy plus chemotherapy (IMRT-C) with chemotherapy-only in this
      patient population. MATERIALS AND METHODS: We randomly assigned patients with D2
      lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups.
      The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body
      surface area per day plus 20mg of leucovorin per square meter of body-surface
      area per day for 5 days, followed by 45 Gy of IMRT for 5 weeks, with fluorouracil
      and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day
      cycles of fluorouracil and leucovorin were given 4 weeks after the completion of
      IMRT. Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C
      group. RESULTS: The median overall survival (OS) in the chemotherapy-only group
      was 48 months, as compared with 58 months in the IMRT-C group; the hazard ratio
      for death was 1.24 (95% confidence interval, 0.94-1.65; P=0.122). IMRT-C was
      associated with increases in the median duration of recurrence-free survival
      (RFS) (36 months vs. 50 months), the hazard ratio for recurrence was 1.35 (95%
      confidence interval, 1.03-1.78; P=0.029). COX multivariate regression analysis
      showed that lymph node metastasis and TNM stage were both the independent
      prognostic factors. Rates of all grade adverse events were similar in the two
      treatment groups. CONCLUSIONS: IMRT-C improved RFS, but did not significantly
      improve OS among patients with D2 lymph node dissection in gastric cancer. Using
      IMRT plus chemotherapy was feasible and well tolerated in patients with gastric
      cancer after D2 resection.

PMID- 22985775
TI  - Membranous expression of activated leukocyte cell adhesion molecule contributes
      to poor prognosis and malignant phenotypes of non-small-cell lung cancer.
AB  - BACKGROUND: Activated leukocyte cell adhesion molecule (ALCAM) has been shown to
      correlate with the prognosis of patients with various types of human
      malignancies. However, the relationship between ALCAM expression and progression
      of non-small-cell lung cancer (NSCLC) has not been investigated. This study was
      designed to clarify the prognostic impact of ALCAM expression of NSCLC cells.
      MATERIALS AND METHODS: The study population consisted of 147 NSCLC patients who
      underwent complete resection. We performed immunohistochemical staining for ALCAM
      expression and correlated this to the clinicopathologic parameters and patient
      survival. The ALCAM expression in NSCLC cell lines was analyzed using
      quantitative reverse transcription-polymerase chain reaction and Western blot
      analyses. ALCAM knockdown in NSCLC cell lines was performed with lentivirus
      mediated short hairpin RNA transduction. RESULTS: Positive membranous and
      cytoplasmic ALCAM expressions were detected in 66 (44.9%) and 57 (38.8%)
      patients, respectively. A significant association of high membranous ALCAM
      expression with shortened overall survival (OS) was found (P = 0.009). However,
      patients with cytoplasmic staining of ALCAM showed no significantly shortened OS
      (P = 0.723). Multivariate analyses showed that membranous expression was adverse
      prognostic factors for OS (hazard ratio, 2.11; P = 0.046). ALCAM knockdown with
      short hairpin RNA suppressed cell migration and invasion of NSCLC cell lines in
      vitro. CONCLUSIONS: Strong membranous ALCAM expression is associated with a poor
      prognosis in patients with resected NSCLC, and overexpression of ALCAM causes
      malignant phenotypes of NSCLC.

PMID- 22985777
TI  - QA makes a clinical trial stronger: evidence-based medicine in radiation therapy.
AB  - Quality assurance (QA) for radiation therapy (RT) in clinical trials is necessary
      to ensure treatment is safely and effectively administered. QA assurance requires
      however substantial human and financial resources, as it has become more
      comprehensive and labor intensive in recent RT trials. It is presumed that RT
      deviations decrease therapeutic effectiveness of the studied regimen. This study
      assesses the impact of RT protocol-deviations on patient's outcome in prospective
      phase II-III RT trials. PubMed, Medline and Embase identified nine prospective RT
      trials detailing QA RT violation and patient's outcome. Planned QA analysis was
      preformed retrospectively and prospectively in eight and one studies,
      respectively. Non-adherence to protocol-specified RT requirements in prospective
      trials is frequent: the observed major deviation rates range from 11.8% to 48.0%
      (mean, 28.1 +/- 17.9%). QA RT deviations had a significant impact on the primary
      study end-point in a majority (62.5%) of studies. The number of patients accrued
      per center was a significant predictive factor for RT deviations in the largest
      series. These QA data stemming from prospective clinical trials show undisputedly
      that non adherence to protocol-specified RT requirements is associated with
      reduced survival, local control and potentially increased toxicity.

PMID- 22985779
TI  - A community call for a dedicated radiobiological research facility to support
      particle beam cancer therapy.

PMID- 22985780
TI  - Spinal cord tolerance to single-session uniform irradiation in pigs: implications
      for a dose-volume effect.
AB  - BACKGROUND AND PURPOSE: This study was performed to test the hypothesis that
      spinal cord radiosensitivity is significantly modified by uniform versus
      laterally non-uniform dose distributions. MATERIALS AND METHODS: A uniform dose
      distribution was delivered to a 4.5-7.0 cm length of cervical spinal cord in 22
      mature Yucatan minipigs for comparison with a companion study in which a
      laterally non-uniform dose was given [1]. Pigs were allocated into four dose
      groups with mean maximum spinal cord doses of 17.5 +/- 0.1 Gy (n=7), 19.5 +/- 0.2
      Gy (n=6), 22.0 +/- 0.1 Gy (n=5), and 24.1 +/- 0.2 Gy (n=4). The study endpoint
      was motor neurologic deficit determined by a change in gait within one year.
      Spinal cord sections were stained with a Luxol fast blue/periodic acid Schiff
      combination. RESULTS: Dose-response curves for uniform versus non-uniform spinal
      cord irradiation were nearly identical with ED(50)'s (95% confidence interval) of
      20.2 Gy (19.1-25.8) and 20.0 Gy (18.3-21.7), respectively. No neurologic change
      was observed for either dose distribution when the maximum spinal cord dose was
      <= 17.8 Gy while all animals experienced deficits at doses >= 21.8 Gy.
      CONCLUSION: No dose-volume effect was observed in pigs for the dose distributions
      studied and the endpoint of motor neurologic deficit; however, partial spinal
      cord irradiation resulted in less debilitating neurologic morbidity and
      histopathology.

PMID- 22985782
TI  - Clinical measures are feasible and sensitive to assess balance and gait
      capacities in older persons with mild to moderate Intellectual Disabilities.
AB  - Mobility limitations are common in persons with Intellectual Disabilities (ID).
      Differences in balance and gait capacities between persons with ID and controls
      have mainly been demonstrated by instrumented assessments (e.g. posturography and
      gait analysis), which require sophisticated and expensive equipment such as force
      plates or a 3D motion analysis system. Most physicians and allied healthcare
      professionals working with persons with ID do not have such equipment at their
      disposal, so they must rely on clinical tests to determine whether balance and
      gait are affected. The aim of this study was to investigate whether existing
      clinical balance and gait tests are feasible in older persons with mild to
      moderate ID and to examine whether these tests are able to show limitations in
      balance and gait capacities in the ID population compared to age-matched peers in
      the general population. Furthermore, it was aimed to identify the most important
      determinants of balance and gait disability in persons with the ID. A total of 76
      older persons with mild to moderate ID (43 male, mean age 63.1 +/- 7.6 years) and
      20 healthy controls (14 male, mean age 62.2 +/- 5.6 years) participated. Balance
      and gait abilities were assessed with the Berg Balance Scale (BBS), the
      Functional Reach test (FR), the Timed Up and Go Test (TUGT), the timed Single Leg
      Stance (SLS) and the Ten Metre Walking Test (TMWT). Our study showed that it is
      feasible to conduct standard clinical balance and gait tests in older persons
      with mild to moderate ID. Balance and gait performance of persons with ID is
      substantially worse compared to older persons of the general population. Age,
      number of co-morbidities, Body Mass Index (BMI), body sway and fear of falling
      are associated with balance and gait performance in persons with ID. These
      factors might help in the selection of subjects to be monitored on their balance
      and gait capacities.

PMID- 22985778
TI  - Effects of lipopolysaccharide on the response of C57BL/6J mice to whole thorax
      irradiation.
AB  - BACKGROUND AND PURPOSE: Inflammatory and fibrogenic processes play a crucial role
      in the radiation-induced injury in the lung. The aim of the present study was to
      examine whether additive LPS exposure in the lung (to simulate respiratory
      infection) would affect pneumonitis or fibrosis associated with lung irradiation.
      MATERIAL AND METHODS: Wildtype C57Bl/6J (WT-C57) and TNFalpha, TNFR1 and TNFR2
      knockout ((-/-)) mice, in C57Bl/6J background, were given whole thorax
      irradiation (10 Gy) with or without post-irradiation intratracheal administration
      of LPS (50MUg/mice). Functional deficit was examined by measuring breathing rate
      at various times after treatment. Real-time Reverse Transcription-Polymerase
      Chain Reaction (RT-PCR) and immunohistochemistry were used to analyze the protein
      expression and m-RNA of Interleukin-1 alpha (IL-1alpha), Interleukin-1 beta (IL
      1beta), Interleukin-6 (IL-6), Tumour Necrosis Factor alpha (TNFalpha) and
      Transforming Growth Factor beta (TGFbeta) in the lung at various times after
      treatment. Inflammatory cells were detected by Mac-3 (macrophages) and Toluidine
      Blue (mast cells) staining. Collagen content was estimated by hydroxyproline
      (total collagen) and Sircol assay (soluble collagen). Levels of oxidative damage
      were assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG) staining. RESULTS: LPS
      exposure significantly attenuated the breathing rate increases following
      irradiation of WT-C57, TNFR1(-/-) and TNFR2(-/-)mice and to a lesser extent in
      TNFalpha(-/-) mice. Collagen content was significantly reduced after LPS
      treatment in WT-C57, TNFR1(-/-) and TNFalpha(-/-) mice and there was a trend in
      TNFR2(-/-) mice. Similarly there were lower levels of inflammatory cells and
      cytokines in the LPS treated mice. CONCLUSIONS: This study reveals a mitigating
      effect of early exposure to LPS on injury caused by irradiation on lungs of C57Bl
      mice. The results suggest that immediate infection post irradiation may not
      impact lung response negatively in radiation-accident victims, however, further
      studies are required in different animal models, and with specific infectious
      agents, to confirm and extend our findings.

PMID- 22985783
TI  - Psychometric properties of the Chinese version of the Autism Spectrum Quotient
      (AQ).
AB  - The Autism Spectrum Quotient (AQ) has been widely used for measuring autistic
      characteristics in parents of children with autism spectrum disorders (ASD).
      Nonetheless, its psychometric validity is yet to be justified. This study tested
      the factor structure of the AQ by means of principal component analysis and
      confirmatory factor analysis using, for the first time, data from 4192 Taiwanese
      parents (1208 with ASD children and 2984 with typically developing children).
      Results yielded a 35-item, 5-dimensional factor solution that had favorable
      psychometric characteristics (RMSEA = .054; NNFI = .962; CFI = .969) than any of
      the previously-published AQ factor solutions. Subscales of this new AQ-Chinese
      model were statistically and semantically coherent, namely: Socialness,
      Mindreading, Patterns, Attention to Details and Attention Switching. The
      psychometric properties of the AQ-Chinese did not change between clinic-based and
      community-based data suggesting good fitting for a continuum of autistic
      expression. Furthermore, the considerable overlap between the AQ-Chinese and the
      AQ factor structures derived previously using student samples indicated
      consistency in the manifestation of the autistic profile across different
      cultures and age groups. Group differences in the AQ-Chinese scores were in line
      with previous studies, i.e. males generally scored radically higher than females
      except in Attention to Details. Interestingly, mothers of ASD children reported
      lower total AQ scores than community mothers yet no significant group difference
      for the fathers. Important research and clinical implications pertinent to
      parents with children with ASD and the utility of the AQ were drawn.

PMID- 22985784
TI  - Transitioning between endothelin receptor blockers: monitoring to ensure a smooth
      transition.

PMID- 22985781
TI  - Innate immune responses to Chlamydia pneumoniae infection: role of TLRs, NLRs,
      and the inflammasome.
AB  - Chlamydiae are important human pathogens that are responsible for a wide rage of
      diseases with a significant impact on public health. In this review article we
      highlight how recent studies have increased our knowledge of Chlamydia pneumoniae
      pathogenesis and mechanisms of innate immunity directed host defense against C.
      pneumoniae infection.

PMID- 22985786
TI  - Papering over the cracks: meta-analysis to define the role of percutaneous
      coronary intervention in patients with stable angina.

PMID- 22985785
TI  - Neither diabetes nor glucose-lowering drugs are associated with mortality after
      noncardiac surgery in patients with coronary artery disease or heart failure.
AB  - BACKGROUND: It is unclear whether diabetes mellitus or use of particular glucose
      lowering agents is associated with increased risk of mortality after noncardiac
      surgery in patients with known cardiac disease. METHODS: We carried out a
      retrospective cohort study using 4 linked administrative databases in the
      province of Alberta, Canada from 1999-2006. RESULTS: Of the 32,834 patients with
      known cardiac disease in our cohort, 9305 (28%) had diabetes. All-cause 30-day
      mortality after noncardiac surgery was 6.4% in patients with diabetes, and 6.1%
      in those without diabetes (multivariate adjusted odds ratio [aOR] 0.97, 95%
      confidence interval [CI], 0.87-1.08). In the 24,037 patients older than 65,
      mortality was 7.5% in individuals with diabetes and 7.5% in those without
      diabetes (5.7% in those taking insulin [aOR, 0.89; 95% CI, 0.70-1.13], 8.0% in
      those using oral agents only [aOR, 1.08; 95% CI, 0.95-1.22]). None of the glucose
      lowering drug classes were associated with perioperative mortality in elderly
      cardiac patients (sulfonylureas aOR, 0.94; 95% CI, 0.76-1.16; metformin aOR,
      0.92; 95% CI, 0.74-1.14; thiazolidinediones aOR, 0.64; 95% CI, 0.40-1.04; insulin
      aOR, 0.83; 95% CI, 0.65-1.08), but use of angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers (aOR, 0.83; 95% CI, 0.75-0.93), beta
      blockers (aOR, 0.82; 95% CI, 0.72-0.93), or statins (aOR, 0.65; 95% CI, 0.55
      0.78) in the 100 days before surgery were associated with lower 30-day mortality.
      CONCLUSIONS: Neither diabetes nor exposure to common classes of glucose-lowering
      drugs preoperatively were associated with increased perioperative mortality in
      cardiac patients undergoing noncardiac surgery. However, cardiac patients not
      using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,
      beta-blockers, or statins preoperatively exhibited higher mortality rates,
      emphasizing the importance of optimizing evidence-based therapy before elective
      surgery in these patients.

PMID- 22985787
TI  - The biological role of inflammation in atherosclerosis.
AB  - The concept of the involvement of inflammation in the pathogenesis of
      atherosclerosis has existed since the 1800s, stemming from sentinel pathologic
      observations made by Rudolf Virchow, Karl Rokitansky, and others. Our
      understanding of the complex role played by immune and inflammatory mediators in
      the initiation and progression of atherosclerosis has evolved considerably in the
      intervening years, and today, a dramatically evolved understanding of these
      processes has led to advances in both diagnostic and prognostic approaches, as
      well as novel treatment modalities targeting inflammatory and immune mediators.
      Therapeutic interventions working through multiple mechanisms involved in
      atheroma pathogenesis, such as statins, which both lower lipids and alter the
      inflammatory milieu in the vessel wall, hold promise for the future. In this
      brief review, we explore the biological role of inflammation in atherosclerosis,
      with a focus on cellular involvement in both acute and chronic inflammation, and
      outline novel biomarkers of inflammation and atherosclerosis with a particular
      focus on the potential application of these novel approaches in improving
      strategies for disease diagnosis and management.

PMID- 22985788
TI  - Duodenoscope entrapped by over-the-scope clip: paradoxical image.

PMID- 22985789
TI  - Unexplained hepatic deterioration--keep in mind hepatitis E virus infection!

PMID- 22985790
TI  - Transcription factors associated with epithelial-mesenchymal transition and
      cancer stem cells in the tumor centre and margin of invasive breast cancer.
AB  - Although tumor surgery aims for a complete resection respecting tumor-specific
      safety distance, in many cases the most peripheral part, the invasion front,
      remains in situ. Tumor cells at the tumor margin lose epithelial properties and
      acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal
      transition (EMT) has been suggested to be of prime importance for tissue and
      vessel invasion. Recently, features of EMT were shown to be linked to cells with
      tumor-founding capability, so- called cancer stem cells (CSC). In this study we
      show that transcription factors associated with EMT markers Snail, Slug, Twist
      and Zeb1 are differentially expressed between normal breast epithelium, ductal
      carcinoma in situ and invasive breast cancer. Both invasive and in situ carcinoma
      expressed less Slug and Twist and more Zeb1 compared to normal epithelium. Using
      fluorescence multi-staining the number of potential CSC among invasive cancer
      cells varied dramatically depending on the staining combination used (18.5% for
      CD44(+)/CD24(-) and 2.4% for CD49f(+)/CD24(+)). Interestingly, neither
      transcription factors associated with EMT nor potential CSC counts varied between
      tumor centre and invasion front. No association of these features with clinical
      outcome was detected. Our results suggest that reliable in situ markers for EMT
      are missing for invasive breast cancer. Alternatively, the process of EMT might
      be activated in tumor cells at the margin as well as the centre. Furthermore, our
      data show that the bio-markers of CSC detect very variable cell populations
      within breast cancer, challenging the assumption of a hierarchical organization
      of CSC in these tumors.

PMID- 22985793
TI  - Disaster curricula in medical education: pilot survey.
AB  - INTRODUCTION: An understanding of disaster medicine and the health care system
      during mass-casualty events is vital to a successful disaster response, and has
      been recommended as an integral part of the medical curriculum by the Association
      of American Medical Colleges (AAMC). It has been documented that medical students
      do not believe that they have received adequate training for responding to
      disasters. The purpose of this pilot study was to determine the inclusion of
      disaster medicine in the required course work of medical students at AAMC schools
      in the United States, and to identify the content areas addressed. METHODS: An
      electronic on-line survey was developed based upon published core competencies
      for health care workers, and distributed via e-mail to the education liaison for
      each medical school in the United States that was accredited by the AAMC. The
      survey included questions regarding the inclusion of disaster medicine in the
      medical school curricula, the type of instruction, and the content of
      instruction. RESULTS: Of the 29 (25.2%) medical schools that completed the
      survey, 31% incorporated disaster medicine into their medical school curricula.
      Of those schools that included disaster medicine in their curricula, 20.7%
      offered disaster material as required course work, and 17.2% offered it as
      elective course work. Disaster medicine topics provided at the highest frequency
      included pandemic influenza/severe acute respiratory syndrome (SARS, 27.5%), and
      principles of triage (10.3%). The disaster health competency included most
      frequently was the ability to recognize a potential critical event and implement
      actions at eight (27.5%) of the responding schools. CONCLUSIONS: Only a small
      percentage of US medical schools currently include disaster medicine in their
      core curriculum, and even fewer medical schools have incorporated or adopted
      competency-based training within their disaster medicine lecture topics and
      curricula.

PMID- 22985791
TI  - The RNA-binding protein Musashi1 affects medulloblastoma growth via a network of
      cancer-related genes and is an indicator of poor prognosis.
AB  - Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during
      the development of the nervous system. Msi1 has been characterized as a stem cell
      marker, controlling the balance between self-renewal and differentiation, and has
      also been implicated in tumorigenesis, being highly expressed in multiple tumor
      types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples
      and found that Msi1 is highly expressed in tumor tissue compared with normal
      cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor
      prognosis. Msi1 expression was determined to be particularly high in molecular
      subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for
      tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs
      reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize
      the participation of Msi1 in medulloblastoma, we conducted different high
      throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray
      analysis (RIP-chip) was used to identify mRNA species preferentially associated
      with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes
      with similar or opposite expression patterns to Msi1 in our medulloblastoma
      cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major
      nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a
      regulator of multiple processes in medulloblastoma formation and could become an
      important therapeutic target.

PMID- 22985794
TI  - Targeted mass spectrometry imaging: specific targeting mass spectrometry imaging
      technologies from history to perspective.
AB  - Since its introduction during the last decade, MALDI mass spectrometry imaging
      (MSI) is now a routine technique in biology. Nevertheless, a missing link exists
      in MALDI MSI. Lipids, peptides/proteins, metabolites and drugs can easily be
      mapped using MALDI-MSI, but this technique has not yet been used to map the
      transcriptome, which includes microRNA, siRNA and other components. This latter
      field of research is now one of the major fields in clinical research and needs
      to be explored using MALDI-MSI. To investigate the transcriptome, a novel imaging
      technique has been developed called Tag-Mass imaging mass spectrometry. The aim
      of this review is to discuss this technique from its history to its place in the
      future of mass spectrometric imaging.

PMID- 22985792
TI  - Enhancement of proinflammatory and procoagulant responses to silica particles by
      monocyte-endothelial cell interactions.
AB  - BACKGROUND: Inorganic particles, such as drug carriers or contrast agents, are
      often introduced into the vascular system. Many key components of the in vivo
      vascular environment include monocyte-endothelial cell interactions, which are
      important in the initiation of cardiovascular disease. To better understand the
      effect of particles on vascular function, the present study explored the direct
      biological effects of particles on human umbilical vein endothelial cells
      (HUVECs) and monocytes (THP-1 cells). In addition, the integrated effects and
      possible mechanism of particle-mediated monocyte-endothelial cell interactions
      were investigated using a coculture model of HUVECs and THP-1 cells. Fe3O4 and
      SiO2 particles were chosen as the test materials in the present study. RESULTS:
      The cell viability data from an MTS assay showed that exposure to Fe3O4 or SiO2
      particles at concentrations of 200 MUg/mL and above significantly decreased the
      cell viability of HUVECs, but no significant loss in viability was observed in
      the THP-1 cells. TEM images indicated that with the accumulation of SiO2
      particles in the cells, the size, structure and morphology of the lysosomes
      significantly changed in HUVECs, whereas the lysosomes of THP-1 cells were not
      altered. Our results showed that reactive oxygen species (ROS) generation; the
      production of interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1 (MCP
      1), tumor necrosis factor (TNF)-alpha and IL-1beta; and the expression of CD106,
      CD62E and tissue factor in HUVECs and monocytes were significantly enhanced to a
      greater degree in the SiO2-particle-activated cocultures compared with the
      individual cell types alone. In contrast, exposure to Fe3O4 particles had no
      impact on the activation of monocytes or endothelial cells in monoculture or
      coculture. Moreover, using treatment with the supernatants of SiO2-particle
      stimulated monocytes or HUVECs, we found that the enhancement of proinflammatory
      response by SiO2 particles was not mediated by soluble factors but was dependent
      on the direct contact between monocytes and HUVECs. Furthermore, flow cytometry
      analysis showed that SiO2 particles could markedly increase CD40L expression in
      HUVECs. Our data also demonstrated that the stimulation of cocultures with SiO2
      particles strongly enhanced c-Jun NH2-terminal kinase (JNK) phosphorylation and
      NF-kappaB activation in both HUVECs and THP-1 cells, whereas the phosphorylation
      of p38 was not affected. CONCLUSIONS: Our data demonstrate that SiO2 particles
      can significantly augment proinflammatory and procoagulant responses through CD40
      CD40L-mediated monocyte-endothelial cell interactions via the JNK/NF-kappaB
      pathway, which suggests that cooperative interactions between particles,
      endothelial cells, and monocytes may trigger or exacerbate cardiovascular
      dysfunction and disease, such as atherosclerosis and thrombosis. These findings
      also indicate that the monocyte-endothelial cocultures represent a sensitive in
      vitro model system to assess the potential toxicity of particles and provide
      useful information that may help guide the future design and use of inorganic
      particles in biomedical applications.

PMID- 22985795
TI  - Cancer as a disease of tissue pattern formation.
AB  - The diagnosis of neoplastic disease still lays its foundations on the detection
      of altered tissue morphology. Most importantly, cancer begins, at least in many
      cases as a disease with altered tissue pattern formation. It is therefore rather
      surprising that the issue regarding the possible mechanistic role of such
      property in the pathogenesis of cancer has received relatively little attention
      so far. To be more specific, we need to ask the following question: is altered
      tissue pattern formation a mere bystander, with its pervasive presence along the
      entire carcinogenic sequence, or does it play a role in fuelling this process?
      Pathways related to morphogenesis and to the establishment of cell polarity will
      be considered for their possible mechanistic involvement in early phases of
      neoplastic disease. Evidences and hypotheses relating altered tissue pattern
      formation to the emergence of the tumor microenvironment and to neoplastic
      progression will be discussed.

PMID- 22985796
TI  - CUB and zona pellucida-like domain-containing protein 1 (CUZD1): a novel
      serological biomarker for ovarian cancer.
AB  - OBJECTIVES: To measure the levels of serum CUB and zona pellucida-like domain
      containing protein 1 (CUZD1) in patients with ovarian cancer (OvCa), benign
      gynecological conditions and healthy women and in a number of other cancer types
      (breast, colorectal, lung, prostate and testicular). DESIGN AND METHODS: Serum
      CUZD1 levels were measured with a commercial enzyme-linked immunosorbent assay
      (ELISA). All specimens were analyzed in duplicate. Preliminary verification was
      performed in serum using 9 healthy women and 20 late stage (III-IV) OvCa
      patients. An independent cohort of serum samples was used to validate the
      verification results (18 late stage OvCa, 8 benign gynecological conditions and 8
      healthy controls). The following specimens were used for the other cancer types
      of unknown stage-breast (n=11), colorectal (n=10), lung (n=10), prostate (n=15)
      and testicular (n=10). RESULTS: Serum CUZD1 was significantly elevated in ovarian
      cancer patients (range 95-668 MUg/L) as compared to healthy controls (range 0.7
      2.5 MUg/L). The independent cohort of OvCa samples confirmed the preliminary
      verification results. CUZD1 was also elevated in breast and lung cancer specimens
      and not in colorectal, prostate and testicular cancer specimens. CONCLUSIONS:
      CUZD1 appears to be a highly promising novel serum biomarker for OvCa diagnosis.
      Its performance in the 2 independent cohorts examined, and in lung and breast
      cancer patients warrants further investigation.

PMID- 22985797
TI  - Discontinuous and continuous purification of single-chain antibody fragments
      using immobilized metal ion affinity chromatography.
AB  - This work describes the adsorption-desorption behavior of a histidine-tagged
      single-chain Fragment variable antibody (D1.3 scFv) on a commercial immobilized
      metal ion affinity chromatography (IMAC) column. A clarified cell culture
      supernatant originating from Bacillus megaterium was characterized using single
      column experiments in a pH-gradient elution mode. The cell culture supernatant
      containing the antibody fragment D1.3 scFv could be treated in the
      chromatographic separation process as a pseudo-binary mixture. Adsorption
      equilibrium constants of the antibody fragment fraction (ABF) and the non
      specifically retained protein impurity fraction (IMP) were determined
      experimentally at constant pH by reinjecting pulses of pooled fractions collected
      in preliminary batch gradient elution runs. Based on the estimated adsorption
      equilibrium constants a possible multicolumn open-loop three-zone two-step pH
      gradient simulated moving bed (SMB) process is suggested and designed, which
      possesses the potential to isolate continuously the antibody fragment fraction
      (ABF) containing the single-chain antibody fragment D1.3 scFv.

PMID- 22985798
TI  - Cell death induced by 7-oxysterols via lysosomal and mitochondrial pathways is
      p53-dependent.
AB  - Oxysterol accumulation and p53 expression mainly in macrophages have been
      associated with cell death and necrotic core formation in human atheroma
      progression. Oxidative stress and lysosomal membrane permeabilization (LMP) in
      macrophages are important causes of macrophage apoptosis. However, it is not
      understood how p53 and oxysterols interact in the process. We show here that 7
      oxysterols induce endogenous full-length p53 and phospho-p53 (p53-Ser15) in both
      nucleus and cytoplasm of THP1 and J774 cells, which is followed by cellular
      oxidative stress and apoptotic cell death. The role of p53 in 7-oxysterol
      mediated cell death is further investigated in temperature sensitive p53
      transfected (M1-t-p53) and in p53-deficient (M1) cells. These results reveal that
      7-oxysterols induce induction and nuclear translocation of p53 in M1-t-p53 cells,
      which in turn enhances LMP, mitochondrial translocation of Bax, mitochondrial
      membrane permeabilization, cytosolic release of cytochrome c, and cell death.
      Most importantly, the above effects of 7-oxysterols were not observed in p53
      deficient M1 cells. The findings reveal that 7-oxysterol-induced cell death
      occurs via p53-dependent pathways. Subsequent p53 nuclear translocation and
      induction of wild-type and phosphorylated p53 are early steps in oxysterol
      induced lysosomal-mitochondrial pathways involved in cell death.

PMID- 22985799
TI  - Africa's inevitable walk to genetically modified (GM) crops: opportunities and
      challenges for commercialization.
AB  - High relative poverty levels in Africa are attributed to the continent's under
      performing agriculture. Drought, low-yielding crop varieties, pests and diseases,
      poor soils, low fertilizer use, limited irrigation and lack of modern
      technologies are among the problems that plague African agriculture. Genetically
      modified (GM) crops may possess attributes that can help overcome some of these
      constraints, but have yet to be fully embraced in the mix of technology solutions
      for African agriculture. Cognizant of this, South Africa, Burkina Faso and Egypt
      are steadily growing GM crops on a commercial scale. Countries like Kenya,
      Nigeria, and Uganda are increasingly field-testing these crops with the view to
      commercialize them. These countries show strong government support for GM
      technology. Progress by these first adopter nations provides an insight as to how
      GM crops are increasingly being viewed as one of the ways in which the continent
      can invigorate the agriculture sector and achieve food security.

PMID- 22985800
TI  - Abnormal apocrine secretory cell mitochondria in a Huntington disease patient.
AB  - Over two decades, a 42-year old woman experienced the gradual onset of choreic
      involuntary movements, dystonia, and tics. Decreased caudate nucleus metabolism
      on 2-deoxyglucose PET scan and a heterozygous 49-CAG repeat expansion within the
      HTT gene established the diagnosis of HD, although no other family history was
      known. An axillary skin biopsy revealed a distinctive abnormality of mitochondria
      limited to the apocrine secretory cells on electron microscopy. All mitochondria
      were transformed into rounded structures with disrupted cristae and prominent
      myelin figures; many were enlarged up to 4 times the normal. Cytoplasm of
      apocrine secretory cells showed an abundance of lipid vacuoles, empty vesicles,
      and dense bodies. Biopsied skeletal muscle histology (light microscopy) was
      normal, as was a mitochondrial metabolism study. Biopsies from other HD patients
      have shown similar mitochondrial changes in cerebral neurons, muscle,
      fibroblasts, and lymphoblasts, adding to evidence for a systemic disturbance of
      mitochondria in HD.

PMID- 22985801
TI  - Hydrophobic collapse overrides Coulombic repulsion in ferricytochrome c
      fibrillation under extremely alkaline condition.
AB  - Tuning of both hydrophobic and electrostatic interactions is thought to be
      important for the initial nucleation and stability of protein aggregates that
      self-assemble to produce amyloid fibrils. Importance of a critical balance of
      these two interactions has indeed been determined under various solution
      conditions of fibrillation, the acidic pH, in particular. To find out if
      fibrillar protein structures could be obtained under extreme alkaline conditions,
      cytochrome c was allowed to fibrillate in 0.1 N NaOH at 50 or 60  degrees C.
      Fibers do grow in alkali, but the fibrillation process depends little on the
      ionic strength of the solution. Illustrative fibril morphology readily obtained
      even in the absence of solvent cations poses the question as to how the severity
      of electrostatic repulsions is overcome to initiate aggregation. It appears that
      intermolecular hydrophobic collapse is so overwhelming that electrostatic
      repulsions are subdued, and the negative charges on protein molecules are
      relocated in a way conducive to fiber growth. This proposal seems consistent with
      computer simulation studies indicating central role of hydrophobic interactions.
      Morphologically, branched fibrils characterized by a wide distribution of
      diameter are assembled by winding two or more protofibrils. The results should
      guide selection of model parameters in theoretical studies of fibrillation.

PMID- 22985802
TI  - Target of rapamycin (TOR) controls vitellogenesis via activation of the S6 kinase
      in the fat body of the tick, Haemaphysalis longicornis.
AB  - Vitellogenin (Vg) synthesis, vitellogenesis, is an essential process for the
      development and reproduction of ticks. Our previous finding led to the hypothesis
      that target of rapamycin (TOR) pathway is important for vitellogenesis in the
      hard tick, Haemaphysalis longicornis. The TOR pathway controls cellular activity
      according to nutrient availability in eukaryotes. TOR, a member of the
      phosphatidylinositol 3-kinase family, is a central player in this pathway. Here,
      we present preliminary evidence that H. longicornis TOR (HlTOR) controls
      vitellogenesis via activation of S6 kinase (S6K) in the fat body. RNA
      interference (RNAi)-mediated gene silencing of HlTOR was undertaken to elucidate
      the involvement of HlTOR in the vitellogenesis of the tick. HlTOR-RNAi caused
      inhibition of S6K phosphorylation in the fat body. HlTOR-RNAi also altered not
      only the expression levels of GATA mRNA and protein but also the intracellular
      localisation of GATA in the fat body. The expression levels of Vg mRNA and
      protein in the fat body of HlTOR-RNAi ticks were significantly lower than those
      in control ticks. In the pre-ovipositional stage, the ovaries of control ticks
      had brown oocytes developing, but those of HlTOR-RNAi ticks were white and
      immature. The haemolymph colour indicated that the amount of Vg was lower in
      HlTOR-RNAi ticks than in the controls. Furthermore, rapamycin inhibited S6K
      phosphorylation and reduced the expression levels of Vg mRNA and protein in the
      fat bodies. Vg proteins were not detected in rapamycin-treated fat bodies in the
      presence of 20-hydroxyecdysone. These results suggest that HlTOR activity is
      critical for vitellogenesis stimulated by 20-hydroxyecdysone.

PMID- 22985803
TI  - Father's parenting and father-child relationship among children and adolescents
      with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Western literature documents impaired father-child interactions in
      addition to strong evidence of impaired mother-child interactions in children
      with attention-deficit/hyperactivity disorder (ADHD). However, the parenting
      process of fathers and their engagement in the Asian family with children with
      ADHD remain unexplored. The authors compared fathering and father-child
      relationships between children with ADHD and those without ADHD and identified
      the correlates of these paternal measures. METHODS: Fathering and father-child
      relationships were compared between 296 children with attention
      deficit/hyperactivity disorder (ADHD) and 229 children without ADHD in Taiwan.
      All child participants and their parents received psychiatric interviews for the
      diagnosis of ADHD and other psychiatric disorders of the children, and their
      fathers were assessed for ADHD, anxiety and depressive symptoms. Both the fathers
      and children reported on the father's parenting style, father-child interactions,
      behavioral problems at home, and perceived family support. RESULTS: The results
      showed that children with ADHD received less affection/care and more
      overprotection and authoritarian control from their fathers. They had less active
      interactions with their fathers, more severe behavioral problems at home; and
      perceived less family support than children without ADHD. Correlates for impaired
      father-child interactions included childhood ADHD symptoms, any comorbidity, age
      at assessment, and the father's neurotic personality and depressive symptoms. In
      addition, the children reported more negatively on fathering and father-child
      interactions than the fathers. CONCLUSIONS: Our findings suggest the negative
      impacts of ADHD on the father's parenting style and father-child interactions.
      Clinical interventions aimed at improving father-child interactions warrant more
      attention.

PMID- 22985804
TI  - Treat to target strategy in rheumatoid arthritis: real benefits.
AB  - Treating rheumatoid arthritis (RA) with a goal or "Treat to target" strategy is a
      therapeutic proposal taken from cardiovascular and endocrine literature. It
      proposes that the therapeutic target in RA should be a state of remission, or an
      alternative goal could be a low disease activity. Rheumatologists should measure
      and register disease activity in every clinical visit and if the goal has not
      been reached, therapeutic adjustments should be made. Current evidence from
      clinical trials and a meta-analysis supports the notion that this strategy has
      important clinical benefits in patients with early RA when compared with routine
      care. It is also described that using protocolized treatment offers greater
      benefits. Recent data from Dutch cohorts is presented showing its successful
      implementation. A discussion is offered on the need of more studies in
      established RA.

PMID- 22985805
TI  - Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung
      injury to reduce pulmonary dysfunction (HARP-2) trial: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Acute lung injury (ALI) is a common devastating clinical syndrome
      characterized by life-threatening respiratory failure requiring mechanical
      ventilation and multiple organ failure. There are in vitro, animal studies and
      pre-clinical data suggesting that statins may be beneficial in ALI. The
      Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung
      injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter,
      prospective, randomized, allocation concealed, double-blind, placebo-controlled
      clinical trial which aims to test the hypothesis that treatment with simvastatin
      will improve clinical outcomes in patients with ALI. METHODS/DESIGN: Patients
      fulfilling the American-European Consensus Conference Definition of ALI will be
      randomized in a 1:1 ratio to receive enteral simvastatin 80 mg or placebo once
      daily for a maximum of 28 days. Allocation to randomized groups will be
      stratified with respect to hospital of recruitment and vasopressor requirement.
      Data will be recorded by participating ICUs until hospital discharge, and
      surviving patients will be followed up by post at 3, 6 and 12 months post
      randomization. The primary outcome is number of ventilator-free days to day 28.
      Secondary outcomes are: change in oxygenation index and sequential organ failure
      assessment score up to day 28, number of non pulmonary organ failure free days to
      day 28, critical care unit mortality; hospital mortality; 28 day post
      randomization mortality and 12 month post randomization mortality; health related
      quality of life at discharge, 3, 6 and 12 months post randomization; length of
      critical care unit and hospital stay; health service use up to 12 months post
      randomization; and safety. A total of 540 patients will be recruited from
      approximately 35 ICUs in the UK and Ireland. An economic evaluation will be
      conducted alongside the trial. Plasma and urine samples will be taken up to day
      28 to investigate potential mechanisms by which simvastatin might act to improve
      clinical outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88244364.

PMID- 22985807
TI  - Introduction: Cancer, aging, and comorbidities.

PMID- 22985806
TI  - Assessment of the in vitro and in vivo genotoxic and antigenotoxic effects of
      pimaradienoic acid in mammalian cells.
AB  - The pimarane-type diterpene, pimaradienoic acid (PA), is known for its diverse
      biological properties such as antimicrobial, anti-inflammatory and trypanocidal.
      A preliminary study was undertaken to investigate in vitro the free radical
      scavenging potential of PA. In addition, the genotoxic potential of PA and its
      ability to modulate genotoxicity induced by doxorubicin (DXR) and methyl
      methanesulfonate (MMS) were studied in Chinese hamster lung fibroblasts (V79
      cells) and in male Swiss mice using the comet and micronucleus assays. The DPPH
      (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay showed that PA exerted no
      antioxidant activity when compared to quercetin. The colony-forming assay using
      V79 cells showed that PA was cytotoxic at concentrations >5.0MUg/mL. Therefore,
      concentrations of 0.625, 1.25, 2.5, and 5.0MUg/mL were used for evaluation of the
      genotoxic and antigenotoxic potential of PA in V79 cells. For genotoxic and
      antigenotoxic assessment in Swiss mice, three PA doses were tested (20, 40, and
      80mg/kg body weight) based on the solubility limit of the diterpene in
      dimethylsulfoxide and water. The in vitro results demonstrated that PA induced
      DNA damage at concentrations of 2.5 and 5.0MUg/mL in the comet assay. However, no
      genotoxic effect was observed in the micronucleus test using V79 cells. In the in
      vivo evaluation of genotoxicity, a significant increase in the frequency of DNA
      damage was observed in hepatocytes of animals treated with the highest PA dose
      (80mg/kg) when compared to the control group, but this difference was not seen in
      the micronucleus test. Furthermore, PA significantly reduced the frequency of DXR
      and MMS-induced micronuclei and extent of DNA damage in in vitro and in vivo
      test systems.

PMID- 22985808
TI  - Impact of age and comorbidity on treatment and outcomes in elderly cancer
      patients.
AB  - Cancer is a prevalent disease in elderly patients, who are also more likely to
      have comorbid illnesses than younger patients. Both increasing age and
      comorbidities are associated with a lower use of aggressive cancer therapies
      including surgery, chemotherapy, and radiation therapy-but age is often the
      stronger determinant. A large proportion of elderly but otherwise healthy cancer
      patients do not receive aggressive treatments. Although there is an
      underrepresentation of elderly patients in clinical trials, the available
      evidence suggests that elderly patients can derive similar survival benefits from
      aggressive treatments as younger patients. For certain cancers and treatments,
      elderly patients may experience higher rates of toxicity and therefore require
      closer monitoring. Patients with comorbid illnesses have worse health-related
      quality of life at baseline but experience a similar health-related quality of
      life decline from treatment as healthier patients. However, patients with
      significant comorbidities are less likely to derive benefit from aggressive
      treatments. There is a need for studies to better identify, at baseline, patients
      who are likely to benefit from and tolerate aggressive treatment. A systematic
      use of sophisticated assessments, such as the geriatric assessment, may allow
      physicians to select appropriate patients and reduce underutilization of
      aggressive treatments in elderly cancer patients.

PMID- 22985809
TI  - Integrating a geriatric evaluation in the clinical setting.
AB  - Older cancer patients-which make the majority of cancer patients-present with a
      highly heterogeneous health status. Therefore, a careful assessment of the
      individual's condition is important in the planning of their oncologic care. In
      this article, a two-step approach is recommended: a short screening test of every
      patient presenting for treatment, and a multidisciplinary evaluation for patients
      screening at risk. Several screening tools that have been tested are described,
      and their relative performance is reviewed: the abbreviated Comprehensive
      Geriatric Assessment, the G8, the Senior Adult Oncology Program 2 questionnaire,
      the Triage Risk Screening Tool, the Vulnerable Elders Survey 13 tool, the
      Groeningen Frailty Index, and the Onco-Geriatric Screening Tool. Indeed, regular
      multidisciplinary meetings are key to optimal management of elderly patients, as
      they modify treatment plans in 1/4 to 1/2 of patients. A practical way of
      implementing a multidisciplinary consultation is reviewed, and future directions
      are discussed.

PMID- 22985810
TI  - Age and comorbidity considerations related to radiotherapy and chemotherapy
      administration.
AB  - Oncological treatment decision-making is a highly complex enterprise integrating
      multiple patient, tumor, treatment, and professional factors with the available
      medical evidence. This management complexity can be exacerbated by the interplay
      of patient age and comorbid non-cancer conditions that can affect patient quality
      of life, treatment tolerance, and survival outcomes. Given the expected increase
      in median age (and associated comorbidity burden) of Western populations over the
      next few decades, the use of evidence-based therapies that appropriately balance
      treatment intensity and tolerability to achieve the desired goal of treatment
      (radical, adjuvant, salvage, or palliative) will be increasingly important to
      health care systems, providers, and patients. In this review, we highlight the
      evidence related to age and comorbidity, as it relates to radiotherapy and
      chemotherapy decision making. We will address evidence as it relates to age and
      comorbidity considerations separately and also the interplay between the factors.
      Clinical considerations to adapt radiation and/or chemotherapy treatment to deal
      with comorbidity challenges will be discussed. Knowledge gaps, future research,
      and clinical recommendation in this increasingly important field are highlighted
      as well.

PMID- 22985811
TI  - Management of older men with clinically localized prostate cancer: the
      significance of advanced age and comorbidity.
AB  - The majority of men diagnosed with prostate cancer are diagnosed later in life.
      Although localized prostate cancer is often an indolent disease, older men are
      more frequently diagnosed with high-risk disease and are more likely to die from
      prostate cancer than younger men. Comorbid medical conditions are also more
      prevalent in the later decades of life and can impact prostate cancer treatment
      tolerance and the likelihood of benefiting from aggressive cancer treatment.
      Older men diagnosed with prostate cancer are at risk for both overtreatment of
      low-risk disease and undertreatment of high-risk disease. Prostate cancer
      management decisions for older patients should be tailored based on an individual
      patient's health status, coexisting medical conditions, life expectancy, and
      tumor characteristics.

PMID- 22985812
TI  - Issues in the curative therapy of breast cancer in elderly women.
AB  - Approximately 20% of new breast cancer cases occur in elderly women. Treatment of
      these patients requires attention to several important details. Importantly,
      these patients often have multiple comorbidities, a different risk-benefit
      profile, unique social barriers to care, higher chances for treatment toxicity,
      and higher risks of receiving less than standard-of-care treatment. Several tools
      now exist to stratify risk of morbidity in elderly patients receiving cancer
      therapies. Modern surgical therapy carries low risks for elderly women, and
      breast-conserving therapy should be offered to appropriate women. Standard
      regimens and schedules of systemic therapy should not be withheld in elderly
      patients on the basis of age alone. Several developments in radiation therapy,
      including the acceptance of hypofractionation and accelerated partial breast
      irradiation in selected women with low-risk disease, offer improved convenience
      and access to care. Radiation therapy may be omitted in elderly women with small
      hormone-sensitive tumors; however, omission may be most appropriate in women aged
      >80 years, those with comorbidities, and those likely to be compliant with
      hormonal therapy.

PMID- 22985813
TI  - Evaluation and management of elderly patients with lung cancer.
AB  - Most patients diagnosed with lung cancer are older than 65 years. Advancing age
      is associated with increased medical and psychosocial issues that increase the
      complexity of care. This article provides a summary and update of work-up and
      management of elderly patients with lung cancer. Patient-related prognostic
      factors with attention to assessment of comorbidity in lung cancer patients are
      reviewed. Recent literature regarding toxicity and advances in locoregional and
      systemic therapies are reviewed, with recommendations for management.

PMID- 22985814
TI  - Impact of age and comorbidities on the treatment of gastrointestinal
      malignancies.
AB  - Gastrointestinal malignancies are generally considered diseases that affect older
      patients, with a peak in incidence in the sixth and seventh decades. Age has
      often been a surrogate to screen patients who may have more difficulty in
      tolerating treatment and the related side effects; however, chronologic age does
      not necessarily correlate with physiological organ impairment or poor performance
      status, both of which can vary substantially between individuals. Therefore, the
      assessment of candidacy for the ability to tolerate optimal cancer treatment
      should focus on the assessment of the extent of comorbidity and functional
      status. The review aims at providing a broad overview of the published literature
      regarding the tolerability and efficacy of standard treatment approaches for the
      most common gastrointestinal malignancies, including esophageal, pancreatic, and
      colorectal cancer, among elderly patients.

PMID- 22985815
TI  - Head and neck cancer in the elderly population.
AB  - Approximately two-thirds of head and neck cancer (HNC) patients present with
      locoregionally advanced stage (III and IV) disease. This requires multimodality
      therapy, including surgery, radiation, and/or chemotherapy. Despite recent
      advances in treatments for HNC, the treatment paradigms in the elderly population
      have not been well defined. These patients may not be considered candidates for
      aggressive multimodality management due to multiple comorbidities, general
      debility, and concerns regarding poor treatment tolerance and toxicities. The aim
      of this review is to highlight some of the pertinent issues in dealing with the
      increasing elderly HNC population, the increasing complexity and toxicities
      associated with combined modality treatments, and how comorbidity and age are
      considered during treatment selection decisions. The challenges being faced
      regarding potential interactions of older age and comorbidity, and their impact
      on prognosis and quality of life are reviewed, with a special emphasis on
      radiation therapy or combined modality therapy. Possible solutions to help
      delineate further areas of study addressing key questions in management of
      elderly HNC patients are discussed.

PMID- 22985816
TI  - Biomarkers of aging and radiation therapy tailored to the elderly: future of the
      field.
AB  - An increasing proportion of cancer care will be delivered to elderly patients.
      There is a wide range of health status among the elderly, and "chronological age"
      may differ substantially from "biological age." Biomarkers of aging may be used
      to better determine a patient's biological age and would have potential clinical
      implications for the treatment of elderly patients with cancer. In this article,
      the authors review the current status of biomarkers related to aging and how
      these biomarkers may relate to treatment decisions for elderly patients with
      cancer. They also discuss potential implementation strategies for such biomarkers
      into future clinical trials.

PMID- 22985817
TI  - Prediction of flavin mono-nucleotide binding sites using modified PSSM profile
      and ensemble support vector machine.
AB  - Flavin mono-nucleotide (FMN) closely evolves in many biological processes. In
      this study, a computational method was proposed to identify FMN binding sites
      based on amino acid sequences of proteins only. A modified Position Specific
      Score Matrix was used to characterize the local environmental sequence
      information, and a visible improvement of performance was obtained. Also, the
      ensemble SVM was applied to solve the imbalanced data problem. Additionally, an
      independent dataset was built to evaluate the practical performance of the
      method, and a satisfactory accuracy of 87.87% was achieved. It demonstrates that
      the method is effective in predicting FMN-binding sites.

PMID- 22985818
TI  - A new technology for separation and recovery of materials from waste printed
      circuit boards by dissolving bromine epoxy resins using ionic liquid.
AB  - Recovery of valuable materials from waste printed circuit boards (WPCBs) is quite
      difficult because WPCBs is a heterogeneous mixture of polymer materials, glass
      fibers, and metals. In this study, WPCBs was treated using ionic liquid (1-ethyl
      3-methylimizadolium tetrafluoroborate [EMIM+][BF4-]). Experimental results showed
      that the separation of the solders went to completion, and electronic components
      (ECs) were removed in WPCBs when [EMIM+][BF4-] solution containing WPCBs was
      heated to 240  degrees C. Meanwhile, metallographic observations verified that
      the WPCBs had an initial delamination. When the temperature increased to 260 
      degrees C, the separation of the WPCBs went to completion, and coppers and glass
      fibers were obtained. The used [EMIM+][BF4-] was treated by water to generate a
      solid-liquid suspension, which was separated completely to obtain solid residues
      by filtration. Thermal analyses combined with infrared ray spectra (IR) observed
      that the solid residues were bromine epoxy resins. NMR (nuclear magnetic
      resonance) showed that hydrogen bond played an important role for [EMIM+][BF4-]
      dissolving bromine epoxy resins. This clean and non-polluting technology offers a
      new way to recycle valuable materials from WPCBs and prevent environmental
      pollution from WPCBs effectively.

PMID- 22985819
TI  - Sorption of Pb(II) and Cu(II) onto multi-amine grafted mesoporous silica embedded
      with nano-magnetite: effects of steric factors.
AB  - Steric factors affecting the mass transfer of Pb(II) and Cu(II) in mesocellular
      silica foams (MSU-F-S) functionalized with multi- (mono-, di-, tri-) amine groups
      and nano-magnetite were investigated through batch experiments. We observed that
      neither the sorption capacities nor the sorption rates were linearly proportional
      to the number of amine groups introduced to a ligand. Unexpectedly, the tri-amine
      grafted samples exhibited lower affinity for both metal cations. These results
      are mainly attributed to two important steric factors, pore blockage and a
      conformational change of available amine groups. The relatively large pore size
      (~30 nm) of MSU-F-S could enable various functional molecules such as amines and
      nano-magnetite to be effectively loaded within the pores. However, their
      excessive densities in the limited pore structure could have adverse effects on
      the transport of metal ions into the mesopores. An intraparticle diffusion model
      was applied to elucidate the mechanisms involved in the sorption process. Our
      results showed that the diffusional mass transfer into the mesopores was
      significantly inhibited in tri-amine grafted samples. The present findings
      further the understanding of steric effects on the transport of cationic metals
      into functionalized mesoporous silica and designing efficient sorbents.

PMID- 22985820
TI  - Enhanced remediation of Cr(VI)-contaminated soil by incorporating a calcined
      hydrotalcite-based permeable reactive barrier with electrokinetics.
AB  - This paper describes the enhanced Cr(VI)-contaminated soil remediation via a
      combination of electrokinetics (EK) with a calcined-hydrotalcite-based permeable
      reactive barrier (PRB). First, this combination proved to be feasible, and
      remarkably facilitated Cr(VI) remediation in a column test. Then, lightly-to
      severely (0.16-1.65 mg/g) Cr(VI)-contaminated soil was remediated in a simulated
      test with the calcined hydrotalcite as the PRB under an voltage of 10-30 V (i.e.
      an electric field intensity of 0.7-2.0 V/cm). The observations demonstrated that
      both PRB and EK are critical to efficient remediation and the high de
      contamination efficiency is supposedly attributed to the synergistic effect, for
      which EK concentrates anionic chromate to the anode region and PRB media
      (calcined hydrotalcite) absorbs and immobilizes it. Thus we have shown that the
      combined PRB-EK system is highly adaptive and effective in remediation of a
      larger area contaminated with chromate and various anionic pollutants.

PMID- 22985823
TI  - Growing Lemna minor in agricultural wastewater and converting the duckweed
      biomass to ethanol.
AB  - Duckweed (Lemna minor) was grown in swine lagoon wastewater and Schenk &
      Hildebrandt medium with a growth rate of 3.5 and 14.1 g m(-2)day(-1) (dry basis),
      respectively detected. The rapid accumulation of starch in duckweed biomass (10
      36%, w/w) was triggered by nutrient starvation or growing in dark with addition
      of glucose. The harvested duckweed biomass (from culture in wastewater) contained
      20.3% (w/w) total glucan, 32.3% (w/w) proteins, trace hemicellulose and
      undetectable lignin. Without prior thermal-chemical pretreatment, up to 96.2%
      (w/w) of glucose could be enzymatically released from both the cellulose and
      starch fractions of duckweed biomass. The enzymatic hydrolysates could be
      efficiently fermented by two yeast strains (self-flocculating yeast SPSC01 and
      conventional yeast ATCC 24859) with a high ethanol yield of 0.485 g g(-1)
      (glucose).

PMID- 22985822
TI  - Efficient decolorization and deproteinization using uniform polymer microspheres
      in the succinic acid biorefinery from bio-waste cotton (Gossypium hirsutum L.)
      stalks.
AB  - Bio-waste cotton (Gossypium hirsutum L.) stalks were converted into succinic acid
      by simultaneous saccharification and fermentation (SSF) using Actinobacillus
      succinogenes 130Z. After 54 h SSF at 40  degrees C and pH 7.0, the production of
      succinic acid was 63 g/L, with 1.17 g/L/h productivity and 64% conversion yield.
      After SSF, a simple method for the decolorization and deproteinization of crude
      SSF broth was developed through adsorption tests of polystyrene (PSt)
      microspheres. Under optimized conditions (5% PSt loading (w/v), pH 4.0, 60 
      degrees C and adsorption time of 40 min), the ratios of decolorization,
      deproteinization and succinic acid loss ratios were 96.6, 84.5 and 4.1%,
      respectively. The method developed will provide a potential approach for large
      scale production of succinic acid from the biomass waste.

PMID- 22985824
TI  - Potential utilization of waste sweetpotato vines hydrolysate as a new source for
      single cell oils production by Trichosporon fermentans.
AB  - The enzymatic hydrolysate of sweetpotato vines (SVH) characterized as an
      effective nutrients supplier with low nitrogen availability was firstly used as a
      substrate by Trichosporon fermentans for single cell oils (SCOs) production.
      Batch-fermentation experiments on various SVH based media suggested that co
      fermentation of SVH and some high-sugar content substrates would be much more
      efficient and less-cost for SCOs production. A lipid yield of 9.6 g l(-1) with a
      lipid content of 35.6% was achieved on the SVH without any addition, while 27.6
      and 17.7 g l(-1) lipid were respectively obtained on the fructose supplemented
      SVH media and the SVH mixed with acid treated wheat straw hydrolysate (WSH). The
      positive effect of SVH on the lipid production of T. fermentans was further
      demonstrated with a kinetic investigation revealing that SVH had a remarkable
      promoting effect on the biomass formation and the substrate uptake.

PMID- 22985825
TI  - Butanol production from hemicellulosic hydrolysate of corn fiber by a Clostridium
      beijerinckii mutant with high inhibitor-tolerance.
AB  - A Clostridium beijerinckii mutant RT66 with considerable inhibitor-tolerance
      obtained by continuous culture was used for butanol production from non
      detoxified hemicellulosic hydrolysate of corn fiber treated with dilute sulfuric
      acid (SAHHC). In fed-batch fermentation, 1.8L of diluted SAHHC containing 10 g/L
      of reducing sugar was provided during the acidogenic phase and 0.2L of
      concentrated SAHHC containing 300 g/L of reducing sugar was provided during the
      solventogenic phase. The mutant produced a total amount of solvents of 12.9 g/L,
      which consisted of 3.1 g/L of acetone, 9.3 g/L of butanol and 0.5 g/L of ethanol.
      A solvent yield of 0.35 g/g sugar and a productivity of 0.18 g/L h in 72 h were
      achieved. The remarkable inhibitor-tolerance of C. beijerinckii RT66 demonstrates
      that this may be an excellent strain for butanol production from ligocellulosic
      materials.

PMID- 22985826
TI  - Phycoremediation and biogas potential of native algal isolates from soil and
      wastewater.
AB  - The present study is a novel attempt to integrate phycoremediation and biogas
      production from algal biomass. Algal isolates, sp. 1 and sp. 2, obtained from
      wastewater and soil were evaluated for phycoremediation potential and mass
      production. The estimated yield was 58.4 sp. 1 and 54.75 sp. 2 tons ha(-1) y(-1).
      The algal isolates reduced COD by >70% and NH3-N by 100% in unsterile drain
      wastewater. Higher productivities of sp. 1 (1.05 g L(-1)) and sp. 2 (0.95 g L(
      1)) grown in wastewater compared to that grown in nutrient media (0.89 g L(-1)
      for sp. 1 and 0.85 g L(-1) for sp. 2) indicate the potential of algal isolates in
      biogas production through low cost mass cultivation. Biogas yield of 0.401-0.487
      m(3) kg(-1) VS added with 52-54.9% (v/v) methane content was obtained for algal
      isolates. These results indicate the possibilities of developing an integrated
      process for phycoremediation and biogas production using algal isolates.

PMID- 22985828
TI  - miHA-Match: computational detection of tissue-specific minor histocompatibility
      antigens.
AB  - Allogenic stem cell transplantation has shown considerable success in a number of
      hematological malignancies, in particular in leukemia. The beneficial effect is
      mediated by donor T cells recognizing patient-specific HLA-binding peptides.
      These peptides are called minor histocompatibility antigens (miHAs) and are
      typically caused by single nucleotide polymorphisms. Tissue-specific miHAs have
      successfully been used in anti-tumor therapy without causing unspecific graft
      versus-host reactions. However, only a small number of miHAs have been identified
      to date, limiting the clinical use. Here we present an immunoinformatics pipeline
      for the identification of miHAs. The pipeline can be applied to large-scale miHA
      screening, for example, in the development of diagnostic tests. Another
      interesting application is the design of personalized miHA-based cancer therapies
      based on patient-donor pair-specific miHAs detected by this pipeline. The
      suggested method covers various aspects of genetic variant detection, effects of
      alternative transcripts, and HLA-peptide binding. A comparison of our
      computational pipeline and experimentally derived datasets shows excellent
      agreement and coverage of the computationally predicted miHAs.

PMID- 22985827
TI  - Enzymatic biodiesel production: an overview of potential feedstocks and process
      development.
AB  - The increased global demand for biofuels has prompted the search for alternatives
      to edible oils for biodiesel production. Given the abundance and cost, waste and
      nonedible oils have been investigated as potential feedstocks. A recent research
      interest is the conversion of such feedstocks into biodiesel via enzymatic
      processes, which have considerable advantages over conventional alkali-catalyzed
      processes. To expand the viability of enzymatic biodiesel production,
      considerable effort has been directed toward process development in terms of
      biodiesel productivity, application to wide ranges of contents of water and fatty
      acids, adding value to glycerol byproducts, and bioreactor design. A cost
      evaluation suggested that, with the current enzyme prices, the cost of catalysts
      alone is not competitive against that of alkalis. However, it can also be
      expected that further process optimization will lead to a reduced cost in enzyme
      preparation as well as in downstream processes.

PMID- 22985829
TI  - The cmbT gene encodes a novel major facilitator multidrug resistance transporter
      in Lactococcus lactis.
AB  - Functional characterization of the multidrug resistance CmbT transporter was
      performed in Lactococcus lactis. The cmbT gene is predicted to encode an efflux
      protein homologous to the multidrug resistance major facilitator superfamily. The
      cmbT gene (1377 bp) was cloned and overexpressed in L. lactis NZ9000. Results
      from cell growth studies revealed that the CmbT protein has an effect on host
      cell resistance to lincomycin, cholate, sulbactam, ethidium bromide, Hoechst
      33342, sulfadiazine, streptomycin, rifampicin, puromycin and sulfametoxazole.
      Moreover, in vivo transport assays showed that overexpressed CmbT-mediated
      extrusion of ethidium bromide and Hoechst 33342 was higher than in the control L.
      lactis NZ9000 strain. CmbT-mediated extrusion of Hoechst 33342 was inhibited by
      the ionophores nigericin and valinomycin known to dissipate proton motive force.
      This indicates that CmbT-mediated extrusion is based on a drug-proton antiport
      mechanism. Taking together results obtained in this study, it can be concluded
      that CmbT is a novel major facilitator multidrug resistance transporter candidate
      in L. lactis, with a possible signaling role in sulfur metabolism.

PMID- 22985830
TI  - Pregnancy detection and monitoring in cattle via combined foetus
      electrocardiogram and phonocardiogram signal processing.
AB  - BACKGROUND: Pregnancy testing in cattle is commonly invasive requiring manual
      rectal palpation of the reproductive tract that presents risks to the operator
      and pregnancy. Alternative non-invasive tests have been developed but have not
      gained popularity due to poor specificity, sensitivity and the inconvenience of
      sample handling. Our aim is to present the pilot study and proof of concept of a
      new non invasive technique to sense the presence and age (limited to the closest
      trimester of pregnancy) of the foetus by recording the electrical and audio
      signals produced by the foetus heartbeat using an array of specialized sensors
      embedded in a stand alone handheld prototype device. The device was applied to
      the right flank (approximately at the intercept of a horizontal line drawn
      through the right mid femur region of the cow and a vertical line drawn anywhere
      between lumbar vertebrae 3 to 5) of more than 2000 cattle from 13 different
      farms, including pregnant and not pregnant, a diversity of breeds, and both dairy
      and beef herds. Pregnancy status response is given "on the spot" from an
      optimized machine learning algorithm running on the device within seconds after
      data collection. RESULTS: Using combined electrical and audio foetal signals we
      detected pregnancy with a sensitivity of 87.6% and a specificity of 74.6% for all
      recorded data. Those values increase to 91% and 81% respectively by removing
      files with excessive noise (19%).Foetus ageing was achieved by comparing the
      detected foetus heart-rate with published tables. However, given the challenging
      farm environment of a restless cow, correct foetus ageing was achieved for only
      21% of the correctly diagnosed pregnant cows. CONCLUSIONS: In conclusion we have
      found that combining ECG and PCG measurements on the right flank of cattle
      provides a reliable and rapid method of pregnancy testing. The device has
      potential to be applied by unskilled operators. This will generate more efficient
      and productive management of farms. There is potential for the device to be
      applied to large endangered quadrupeds in captive breeding programs where early,
      safe and reliable pregnancy diagnosis can be imperative but currently difficult
      to achieve.

PMID- 22985831
TI  - Comparison of corneal astigmatism and axis location in cataract patients measured
      by total corneal power, automated keratometry, and simulated keratometry.
AB  - PURPOSE: To compare the corneal astigmatism (magnitude and axis location) derived
      by total corneal power (TCP), automated keratometry, and simulated keratometry.
      SETTING: Siriraj Hospital, Mahidol University, Bangkok, Thailand. DESIGN:
      Prospective comparative study. METHODS: Eyes with previous ocular surgery or
      abnormalities were excluded. All patients were examined with the ARK 730A
      autokeratometer and the Galilei analyzer. The steepest and flattest corneal power
      along with the steepest axis of the TCP, automated keratometry, and simulated
      keratometry were recorded. Vector analysis (J0 and J45) was calculated. Analysis
      of variance with Bonferroni correction was performed for multiple comparisons.
      Outcome measures were the magnitude and axis location of astigmatism. RESULTS:
      One hundred eyes of 100 cataract patients were randomly selected. There was no
      statistically significant difference in the mean steepest axis between TCP (93.31
      +/- 68.75 [SD]), automated keratometry (94.24 +/- 64.78), and simulated
      keratometry (92.42 +/- 64.30). However, the mean magnitude of astigmatism
      measured by TCP (1.23 +/- 0.75) was significantly higher than that measured by
      automated keratometry (0.93 +/- 0.68) (P=.01) but not than that measured by
      simulated keratometry (1.08 +/- 0.68) (P=.43); there was no statistically
      significant difference in J0 or J45. Twenty two (40%) of 54 eyes with more than
      1.00 diopter of TCP astigmatism had more than 10 degrees of axis difference from
      automated keratometry. CONCLUSIONS: The magnitude of TCP astigmatism was higher
      than that of automated keratometry. The axis location was similar. However, there
      was more than 10 degrees of axis difference between automated keratometry and TCP
      in patients with high astigmatism. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 22985832
TI  - Hirschsprung disease (HD) remains a significant surgical and medical challenge
      for pediatric surgeons. Introduction.

PMID- 22985833
TI  - Laparoscopic and transanal pull-through for Hirschsprung disease.
AB  - The surgical correction of Hirschsprung disease has undergone a complete
      evolution in the past decade. Refinements in the performance of both transanal
      and laparoscopic procedures have tremendously facilitated the advancement of
      these surgeries. This chapter presents the history of these procedures, and then
      discusses the various approaches and details of these techniques.

PMID- 22985834
TI  - Transitional zone pull through: surgical pathology considerations.
AB  - Incomplete resection of the transitional zone (TZ) between histologically normal
      and aganglionic bowel in Hirschsprung disease is a putative cause of
      postoperative dysmotility. A review of literature indicates that diverse
      histopathological indexes have been used to define the TZ, and validated and
      reproducible diagnostic criteria have not been established. As a consequence, the
      proximal margin of the TZ is difficult to delimit, and the length of the TZ in a
      given patient depends on the diagnostic criteria used. Seromuscular biopsies are
      inadequate to exclude TZ, as diagnostic indexes may involve only a portion of the
      bowel circumference or the submucosa. Most published investigations of
      postoperative outcome after a TZ pull through (TZPT) conclude that the latter can
      cause persistent obstructive symptoms, which necessitate reoperation. However,
      the results of these studies are difficult to translate into clinical practice
      because most lack appropriate controls, and the overwhelming majority provide
      inadequate histopathological descriptions for reference at the time of
      intraoperative frozen section analysis. At present, a conservative approach based
      on frozen section examination of the entire proximal margin of the resection to
      exclude obvious subcircumferential aganglionosis (contiguous gap between ganglia
      of more than one-eighth of the circumference), hypoganglionosis (continuous
      string of myenteric ganglia comprised of 1 or 2 ganglion cells without
      surrounding neuropil), or hypertrophic submucosal nerves (>2 nerves with widths
      >=40 MUm per high-power field) seems prudent. Well-controlled studies to
      correlate proximal margin histology, especially subtle anatomic or
      immunohistochemical changes, with postoperative outcome are needed.

PMID- 22985835
TI  - Total colonic aganglionosis in Hirschsprung disease.
AB  - Total colonic aganglionosis (TCA) is a relatively uncommon form of Hirschsprung
      disease (HSCR), occurring in approximately 2%-13% of cases. It can probably be
      classified as TCA (defined as aganglionosis extending from the anus to at least
      the ileocecal valve, but not >50 cm proximal to the ileocecal valve) and total
      colonic and small bowel aganglionosis, which may involve a very long segment of
      aganglionosis. It is not yet clear whether TCA merely represents a long form of
      HSCR or a different expression of the disease. There are many differences between
      TCA and other forms of HSCR, which require explanation if its ubiquitous clinical
      features are to be understood. Clinically, TCA appears to represent a different
      spectrum of disease in terms of presentation and difficulties that may be
      experienced in diagnosis, suggesting a different pathophysiology from the more
      common forms of HSCR. There is also some evidence suggesting that instead of
      being purely congenital, it may represent certain different pathophysiologic
      mechanisms. This study, in addition to reviewing current understanding and
      differences between TCA and the more frequently encountered rectosigmoid (or
      short-segment) expression, correlates them with what is currently known about the
      genetic and molecular biological background. Moreover, it reviews current
      outcomes to find consensus on management.

PMID- 22985836
TI  - Variants of Hirschsprung disease.
AB  - Variants of Hirschsprung disease are conditions that clinically resemble
      Hirschsprung disease, despite the presence of ganglion cells in rectal suction
      biopsies. The characterization and differentiation of various entities are mainly
      based on histologic, immunohistochemical, and electron microscopy findings of
      biopsies from patients with functional intestinal obstruction. Intestinal
      neuronal dysplasia is histologically characterized by hyperganglionosis, giant
      ganglia, and ectopic ganglion cells. In most intestinal neuronal dysplasia cases,
      conservative treatments such as laxatives and enema are sufficient. Some patients
      may require internal sphincter myectomy. Patients with the diagnosis of isolated
      hypoganglionosis show decreased numbers of nerve cells, decreased plexus area, as
      well as increased distance between ganglia in rectal biopsies, and resection of
      the affected segment has been the treatment of choice. The diagnosis of internal
      anal sphincter achalasia is based on abnormal rectal manometry findings, whereas
      rectal suction biopsies display presence of ganglion cells as well as normal
      acetylcholinesterase activity. Internal anal sphincter achalasia is either
      treated by internal sphincter myectomy or botulinum toxin injection. Megacystis
      microcolon intestinal hypoperistalsis is a rare condition, and the most severe
      form of functional intestinal obstruction in the newborn. Megacystis microcolon
      intestinal hypoperistalsis is characterized by massive abdominal distension
      caused by a largely dilated nonobstructed bladder, microcolon, and decreased or
      absent intestinal peristalsis. Although the outcome has improved in recent years,
      survivors have to be either maintained by total parenteral nutrition or have
      undergone multivisceral transplant. This review article summarizes the current
      knowledge of the aforementioned entities of variant HD.

PMID- 22985837
TI  - The pathogenesis of Hirschsprung's disease-associated enterocolitis.
AB  - Hirschsprung's disease-associated enterocolitis (HAEC) remains the most life
      threatening complication in Hirschsprung disease (HD) patients. The pathogenesis
      of HAEC has not been determined and many hypotheses regarding the etiology of
      HAEC have been proposed. These include a possible causal relationship between the
      abnormal enteric nervous system development in HD and the development of
      enterocolitis. Based on the complex genetic causes of HD that have been
      discovered and the resultant heterogeneous group of patients that exists, the
      causes of HAEC are likely multiple. New insights regarding the relationship of
      the role of the enteric nervous system and its interaction between intestinal
      barrier function, innate host immunity, and commensal microflora have been
      discovered, which may shed light on this perplexing problem. This review presents
      current known risk factors of HAEC and the proposed theories and supporting
      evidence for the potential etiologies of HAEC.

PMID- 22985839
TI  - Long-term outcomes of Hirschsprung's disease.
AB  - Despite significant developments in the understanding of the pathologic anatomy
      and physiology of Hirschsprung's disease (HD), the results of surgical therapy
      remain far from perfect. The functional defects and psychosocial difficulties
      that occur commonly in children with HD are passed on to adulthood in a
      significant proportion of patients. Recent prospective and adequately controlled
      cross-sectional studies reveal that constipation and fecal soiling are common
      late sequelae in adulthood. HD patients show uniformly lower scores of overall
      bowel function than healthy control subjects. Functional outcome and quality of
      life may be interrelated and deteriorate with increasing age. Despite these
      shortcomings, at adult age, most of the HD patients appear to be able to function
      as normal members of the society in terms of psychosocial, occupational, and
      recreational activities. Patients are at risk of developing related conditions,
      such as cancer, that require planning of specific screening programs. Many of the
      long-term problems that these patients experience are specific to HD. The follow
      up of HD patients should be performed by medical personnel familiar with the
      disease, preferably in a specialized referral center, and the follow-up should
      continue beyond childhood.

PMID- 22985838
TI  - Hirschsprung-associated enterocolitis: prevention and therapy.
AB  - Hirschsprung-associated enterocolitis remains the greatest cause of morbidity and
      mortality in children with Hirschsprung disease. This chapter details the various
      approaches used to treat and prevent this disease process. This includes
      prevention of complications, such as stricture formation, prophylaxis with rectal
      washouts, and identification of high-risk individuals. The chapter also details
      approaches to diagnose Hirschsprung-associated enterocolitis as well as to
      exclude other etiologies.

PMID- 22985840
TI  - The Hirschsprungs patient who is soiling after what was considered a "successful"
      pull-through.
AB  - After surgery for Hirschsprungs disease, most children thrive, have few if any
      episodes of abdominal distention and enterocolitis, and are fecally continent.
      However, there exists a small group of patients who do not do well. Either they
      suffer from persistent distension and enterocolitis or they experience soiling
      after their pull-through procedure. These patients can be systematically
      evaluated and successfully treated with a combination of bowel management,
      dietary changes, and laxatives, and, in certain circumstances, a reoperation.

PMID- 22985841
TI  - Reoperative surgery for Hirschsprung disease.
AB  - Despite most children undergoing a successful pull through for Hirschsprung
      disease, a small portion of children are left with persistent stooling issues.
      Most of these stooling issues can be addressed by nonoperative approaches.
      However, in a small group of remaining children, a reoperation may be necessary.
      Most children who may need a redo pull-through procedure may have a persistent
      area of aganglionosis, unremitting enterocolitis, or a torsion or stricture of
      the pull-through segment. Each of these influences the approach the surgeon must
      take to correct the presenting problem. The chapter details the diagnostic
      approach as well as the operative techniques, which best deal with each of these
      complications.

PMID- 22985842
TI  - Future therapies for Hirschsprung's disease.
AB  - The current management of Hirschsprung's disease (HSCR) is still associated with
      significant long-term morbidities despite on-going refinements in surgical care.
      Over the course of the past 20 years, significant inroads have been made in our
      understanding of the development of the enteric nervous system and what factors
      are responsible for the development of HSCR. This has prompted increased interest
      in the possibility of using this knowledge to develop new alternative and
      adjunctive therapies for HSCR. The aim of this review is to provide an overview
      of the current progress being made toward the development of future therapies to
      improve the outcome for children with HSCR.

PMID- 22985844
TI  - [Amenable mortality as indicator of effectiveness of health care services in
      Spain before and after transferences].
AB  - OBJECTIVE: To describe the evolution of amenable mortality (MRASS) in Spain and
      to evaluate differences in trend patterns before and after health care services
      were transferred to local authorities. METHODS: MRASS was defined from a list of
      causes of death used in other studies. We analyzed the change in sex-age
      standardized death rates of MRASS in two periods: 1999-2001 and 2006-2008, just
      before, and five years after, the health care transfers were completed. RESULTS:
      MRASS represented 24% of deaths in persons from 0 to 74 years old. MRASS has seen
      a reduction (19.4%) between the two periods over and above other causes of
      mortality (14.5%). The group of causes of mortality which showed most reduction:
      ischemic heart disease (28%), other vascular disease (27%), surgical conditions
      and surgical-medical errors (26%), and diabetes (22.5%). Although there were
      differences between the districts, health care transfers have not created
      significant variations in MRASS. Navarra and Madrid showed lower rates of MRASS,
      and the Canary Islands, Asturias, Andalusia, Ceuta and Melilla had higher rates.
      The Balearic Islands showed the greatest reduction in MRASS. CONCLUSIONS: MRASS
      constitutes an important proportion of trends of mortality in persons between 0
      74 years. It has declined in all districts. Even though there were large
      differences between districts, there does not appear to be any direct influence
      due to health care transfer in amenable mortality trends. In spite of
      limitations, MRASS is an indicator to be considered when monitoring and detecting
      weaknesses in the effectiveness of health care systems.

PMID- 22985845
TI  - Activated microglia are implicated in cognitive deficits, neuronal death, and
      successful recovery following intermittent ethanol exposure.
AB  - Microglia function as the primary immune effector cells in the brain and play a
      pivotal role in the neuroinflammatory processes which are critical component of
      neurodegenerative diseases. Alcohol abuse has been considered as one of the
      common reasons for neurodegeneration although the causative factors are poorly
      understood. Here, we investigated whether activated microglia were implicated in
      neurodegeneration and cognitive dysfunctions in adult rats after intermittent
      alcohol abuse. Rats were given orally a priming dose of 5 g/kg ethanol and then
      3g/kg every 8h for 4 days, followed by a 3-day ethanol-withdrawal period. These 4
      days of ethanol treatments were repeated four times intermittently to simulate
      the binge drinking of human alcoholics. Neurodegeneration and microglial
      activation were detected by Fluoro-Jade B staining, Golgi staining,
      immunohistochemistry and ELISA, respectively, while cognitive function was
      assessed by Morris water maze and novel object recognition. The results showed
      that microglial activation and inflammatory cytokine expression were obvious in
      the parietal association cortex, entorhinal cortex and hippocampus accompanied by
      neurodegeneration following ethanol treatment. Moreover, learning and memory
      abilities also declined following ethanol treatments. However, the hypertrophied
      microglia disappeared accompanied by the decrease of inflammatory cytokines
      levels on day 4, and ramified microglial proliferated significantly on day 14
      after ethanol withdrawal, along with a recovery from neuronal damage and
      cognitive impairment. Thus, the present study indicated that activated microglia
      might be involved in neurodegeneration and cognitive dysfunctions induced by
      intermittent ethanol exposure, and neurotrophic microglia appear to have a
      contribution to the recovery during abstinence.

PMID- 22985846
TI  - Investigation and optimization of the novel UASB-MFC integrated system for
      sulfate removal and bioelectricity generation using the response surface
      methodology (RSM).
AB  - COD/sulfate ratio and hydraulic residence time (HRT), both of which influence
      sulfate loadings jointly, are recognized as the most two important affecting
      factors for sulfate removal and bioelectricity generation in the novel up-flow
      anaerobic sludge blanket reactor-microbial fuel cell (UASB-MFC) integrated
      system. The response surface methodology (RSM) was employed for the optimization
      of this system and the optimum condition with COD/sulfate ratio of 2.3 and HRT of
      54.3h was obtained with the target of maximizing the power output. In terms of
      maximizing the total sulfate removal efficiency, the obtained optimum condition
      was COD/sulfate ratio of 3.7 and HRT of 55.6h. Experimental results indicated the
      undistorted simulation and reliable optimized results. These demonstrated that
      RSM was effective to evaluate and optimize the UASB-MFC system for sulfate
      removal and energy recovery, providing a promising guide to further improvement
      of the system for potential applications.

PMID- 22985847
TI  - Microwave pretreatment of defatted rice bran for enhanced recovery of total
      phenolic compounds extracted by subcritical water.
AB  - Enhanced recovery of total phenolics (TP) from defatted rice bran (DRB) subjected
      to prior microwave pretreatment was achieved by subcritical water extraction
      (SWE). The effects of microwave pretreatment temperature (60-100 degrees C) and
      duration (0-30 min) were determined at raw material:water ratios (1:2 and 1:5)
      for SWE under fixed conditions. Optimal extraction was observed at 80 degrees C
      (for 10 min, at a ratio of 1:2). With pretreatment carried out under these
      conditions, a shorter extraction time of 10 min was required for SWE at 200
      degrees C. Combining both optimized conditions, a TP yield of 190.4+/-3.3 mg/g of
      DRB was achieved, some 55% more than was found to be extractable from un
      pretreated samples. The antioxidant activity of the extract was also greater, as
      indicated by a corresponding decrease in IC(50) from 38.8+/-0.4 to 27.7+/-0.5
      MUg/ml.

PMID- 22985848
TI  - Use of non-native phenazines to improve the performance of Pseudomonas aeruginosa
      MTCC 2474 catalysed fuel cells.
AB  - One of the bottlenecks to performance of microbial fuel cells (MFC) has been the
      low electron transfer from bacterial cell membrane or membrane organelle to
      anode. In this study, the effect of phenazines, a class of secondary metabolites
      was examined on the power generation in Pseudomonas aeruginosa MTCC 2474
      catalysed MFC with graphite electrodes. Different metal salt-doped graphite epoxy
      composite electrodes (MS-GECE) were tested in phenazine supplemented MFC. With
      Cu(2+)-GECE as anode in oxychloraphin and tubermycin supplemented MFC, power
      density generated was 7831+/-112.5 and 2096.5+/-11.8 MUW/m(2) respectively.
      However, the addition of native phenazines (pyocyanin and pyorubin) which are
      normally produced by the bacteria was not very helpful in performance of the MFC.
      Also, the addition of these phenazines inhibited the growth of bacteria as well.
      Thus, choice of an appropriate secondary metabolite can have a positive influence
      as a mediator of electron transfer in the working of MFCs.

PMID- 22985849
TI  - Validation and application of HPLC-ESI-MS/MS method for the quantification of
      RBBR decolorization, a model for highly toxic molecules, using several fungi
      strains.
AB  - A novel analytical method using HPLC-MS/MS operating in selected reaction
      monitoring (SRM) for evaluation of fungi efficacy to decolorize Remazol Brilliant
      Blue R (RBBR) dye solution was developed, validated and applied. The method shows
      high sensibility allowing the detection of 4.6 pM of RBBR. Four fungal strains
      were tested in liquid medium, three strains of Aspergillus (Aspergillus
      aculeatus, Aspergillus flavus and Aspergillus fumigatus) and Phanerochaete
      chrysosporium. All fungi were able to degrade the dye, with efficiencies ranging
      from 40% for P. chrysosporium up to 99% for A. flavus during a 30-day incubation
      period. During the experiment, increased accumulation of degradation products was
      observed in A. flavus cultures containing RBBR. Through the use of full scan HPLC
      MS technique it was possible to propose the biogenesis of the microbial metabolic
      degradation pathway. Screening using microorganisms and RBBR may be hereafter
      used to investigate microbial biodegradation of high toxicity molecules such as
      dioxins.

PMID- 22985850
TI  - Isolation of a thermophilic bacterium, Geobacillus sp. SH-1, capable of degrading
      aliphatic hydrocarbons and naphthalene simultaneously, and identification of its
      naphthalene degrading pathway.
AB  - A thermophilic naphthalene- and aliphatic hydrocarbon-degrading bacterium SH-1
      was isolated from a deep oil well and identified as Geobacillus sp. n-alkanes
      from C12 to C33 in crude oil and naphthalene were effectively degraded by strain
      SH-1, and this strain could readily utilize these compounds as its sole carbon
      and energy resources. During the degradation of naphthalene, strain SH-1
      initiated its attack on naphthalene by a monooxygenation at its C-1 to give 1
      naphthol and further monooxygenation at C-2 to produce 1,2-dihydroxynaphthalene.
      The ring of 1,2-dihydroxynaphthalene was cleaved to form trans-o
      hydroxybenzylidenepyruvate. Subsequently, trans-o-hydroxybenzylidenepyruvate was
      transformed to (2E)-3-(2-hydroxyphenyl)prop-2-enal by losing a carboxyl group.
      Additionally, benzoic acid was identified as an intermediate in the naphthalene
      degradation pathway of this Geobacillus strain. This study highlights an
      important potential use of the thermophilic degradative strain SH-1 in the
      cleanup of environmental contamination by naphthalene and crude oil and presents
      a mechanism for naphthalene metabolism.

PMID- 22985851
TI  - Reducing odorous VOC emissions from swine manure using soybean peroxidase and
      peroxides.
AB  - The objective of the research was to determine the optimum application rates of
      soybean peroxidase (SBP) plus peroxide (SBPP) for reducing odorous VOC emissions
      from swine manure. Industrial-grade SBP was applied in combination with liquid
      hydrogen peroxide (H(2)O(2)) or powdered calcium peroxide (CaO(2)) to standard
      phenolic solutions and swine manure, and emissions were measured in a wind
      tunnel. The primary odorant in the untreated manure was 4-methylphenol, which
      accounted for 68-81% of the odor activity value. At the optimum application rate
      of SBPP (50 g L(-1)), 4-methylphenol emissions were reduced from the swine manure
      by 62% (H(2)O(2)) and 98% (CaO(2)) after 24h (P<0.0001). The CaO(2) had a longer
      residence time, remaining effective for 48 h with 92% reduction in emission rates
      (P<0.0001), while H(2)O(2) was similar to the control at 48 h (P=0.28).

PMID- 22985852
TI  - Alkaline pretreatment methods followed by acid hydrolysis of Saccharum spontaneum
      for bioethanol production.
AB  - Different alkaline pretreatment methods (NaOH, NaOH+10% urea and aqueous ammonia)
      were optimized for maximum delignification of Saccharum spontaneum at 30 degrees
      C. Maximum delignification were obtained as 47.8%, 51% and 48% from NaOH (7%
      NaOH, 48h, and 10% biomass loading), NaOH+urea (7% NaOH+10% urea, 48 h and 10%
      biomass loading) and 30% ammonia (40 days and 10% biomass loading) respectively.
      H(2)SO(4) 60% (v/v), 10% biomass loading at 30 degrees C for 4h, were optimized
      conditions to solubilize the cellulose and hemicellulose from solid residue
      obtained after different optimized alkaline pretreatments. Slurry thus obtained
      was diluted to obtain final acid concentration of 10% (v/v) for real hydrolysis
      of cellulose and hemicellulose at 100 degrees C for 1h. Among all pretreatment
      methods applied, the best result 0.58 g (85%) reducing sugars/g of initial
      biomass after acid hydrolysis was obtained from aqueous ammonia pretreated
      biomass. Scheffersomyces stipitis CBS6054 was used to ferment the hydrolysate;
      ethanol yield (Y(p/s)) and productivity (r(p)) were found to be 0.35 g/g and 0.22
      g/L/h respectively.

PMID- 22985854
TI  - A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health
      threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein,
      we report a new category of dideoxy pyrimidine nucleosides possessing a 4'
      carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as
      potential antiviral agents. For the first time, these nucleosides are recognized
      to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'
      didehydrothymidine (16) was most effective against DHBV, HBV and HCV.
      Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl
      group (17) did not affect the anti-HBV activity but greatly increased the anti
      HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined
      with ribavirin without toxicity. The activity exhibited by a single agent towards
      both hepatitis viruses and no detectable in vitro cytotoxicity make this new
      class of compounds of interest.

PMID- 22985853
TI  - Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: synthesis and SAR
      study as tyrosine kinase c-Met inhibitors.
AB  - Two series of new analogues were designed by replacing the quinoline scaffold of
      our earlier lead 2 (zgw-atinib) with quinoxaline and pyrido[2,3-d]pyrimidine
      frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline
      series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a-c possessing an O
      linkage were inactive, whilst the N-linked analogues 15a-c retained c-Met
      inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b
      that showed an IC(50) value of 6.5 nM. Further structural modifications based on
      this compound were undergoing.

PMID- 22985855
TI  - An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for
      stromelysin-1.
AB  - Fragment based drug discovery remains a successful tool for pharmaceutical lead
      discovery. Although based upon the principle of thermodynamic additivity, the
      underlying thermodynamic basis is poorly understood. A thermodynamic additivity
      analysis was performed using stromelysin-1 and a series of biphenyl hydroxamate
      ligands identified through fragment additivity. Our studies suggest that, in this
      instance, additivity arises from enthalpic effects, while interaction entropies
      are unfavorable; this thermodynamic behavior is masked by proton transfer.
      Evaluation of the changes in constant pressure heat capacities during binding
      suggest that solvent exclusion from the binding site does not account for the
      dramatic affinity enhancements observed.

PMID- 22985856
TI  - Amelioration of rotenone-induced dopaminergic cell death in the striatum by
      oxytocin treatment.
AB  - Oxytocin (OT) is essentially associated with uterine contraction during
      parturition and milk ejection reflex. Although several studies implicate the role
      of OT in anti-inflammatory, anti-oxidative and anti-apoptotic pathways, there is
      a lack of data with regard to the protective effects of oxytocin in
      neurodegenerative models such as Parkinson's disease (PD). The present study was
      undertaken to investigate the neuroprotective effects of oxytocin (OT) on
      rotenone-induced PD in rats. Twenty adult Sprague-Dawley rats were injected with
      rotenone (3 MUg/MUl in DMSO) or vehicle (1 MUl DMSO) into the left substantia
      nigra pars compacta (SNc) and ventral tegmental area (VTA) under stereotaxic
      surgery, and PD model was assessed by rotational test ten days after drug
      infusion. The valid PD rats were randomly divided into two groups; Group 1 (n=7)
      and Group 2 (n=7) were administered saline (1 ml/kg/day, i.p.) and oxytocin (160
      MUg/kg/day, i.p.) through 20 days, respectively. The effects of OT treatment were
      evaluated by behavioral, histological and immunohistochemical parameters.
      Apomorphine-induced stereotypic rotations in PD rats were significantly inhibited
      by OT treatment (p<0.05). In addition, immunohistochemical studies clearly
      demonstrated the suppression of Bax, caspase-3, caspase-8 and elevation of Bcl-2
      and tyrosine hydroxylase immunoexpression in OT-treated rats compared to saline
      group. Our findings suggest that oxytocin may have cytoprotective and restorative
      effects on dopaminergic neurons against rotenone-induced injury. The underlying
      mechanism may be associated with the inhibition of apoptotic pathways.

PMID- 22985857
TI  - Advances and prospects of anginex as a promising anti-angiogenesis and anti-tumor
      agent.
AB  - Anginex, a novel artificial cytokine-like peptide (betapep-25), is designed by
      using basic folding principles and incorporating short sequences from the beta
      sheet domains of anti-angiogenic agents, including platelet factor-4 (PF4),
      interleukin-8 (IL-8), and bactericidal-permeability increasing protein 1 (BP1).
      Anginex can specially block the adhesion and migration of the angiogenically
      activated endothelial cells (ECs), leading to apoptosis and ultimately to the
      inhibition of angiogenesis and tumor growth. In vitro and in vivo studies have
      proved its inhibitory effects on the formation of new blood vessels and tumor
      growth even though the mechanism is not clear. The inhibitory effects of anginex
      can be enhanced when it is applied in combination with other therapies, such as
      chemotherapy, radiotherapy and other anti-angiogenic agents. The limitations of
      anginex, including poor stability, short half life, complicated synthesis and low
      purity, have been conquered by modifying its structure or designing novel
      compound anginex and recombinant anginex, which makes possible the clinical
      application of anginex. Here, we summarize the basic and preclinical trials of
      anginex and discuss the prospects of anginex in clinical application. We come to
      the conclusion that anginex and compound or recombinant anginex can be used as
      effective anti-angiogenic agents.

PMID- 22985859
TI  - Interplay between behavioural thermoregulation and immune response in mealworms.
AB  - Since the preferential body temperature should positively correlate with
      physiological performance, behavioural fever should enhance an organism's immune
      response under an immune challenge. Here we have studied the preferential body
      temperature (T(p)) and its consequences on immune response performance after an
      immune challenge in larvae of Tenebrio molitor. We evaluated T(p) and immune
      responses of larvae following a challenge with various concentrations of
      lipopolysaccharide (LPS), and we studied the correlation between T(p) and two
      immune traits, namely antibacterial and phenoloxidase (PO) activities. Larvae
      that were immune challenged with higher LPS concentrations (C(50) and C(100))
      preferred in average, warmer temperatures than did larvae challenged with lower
      concentrations (C(0) and C(25)). T(p) of C(25)-C(100) (challenged)-mealworms was
      2.3 degrees C higher than of C(0) (control) larvae. At lower LPS concentration
      immune challenge (C(0) and C(25)) antibacterial activity correlated positively
      with T(p), but at C(50) and C(100) correlation was lose. PO activity was higher
      at higher LPS concentration, but its magnitude of response did not correlate with
      T(p) Our data suggest that behavioural fever may have a positive effect on host
      performance by enhancing antibacterial response under a low pathogen load
      situation.

PMID- 22985858
TI  - Activation of tachykinin, neurokinin 3 receptors affects chromatin structure and
      gene expression by means of histone acetylation.
AB  - The tachykinin, neurokinin 3 receptor (NK3R) is a g-protein coupled receptor that
      is broadly distributed in the nervous system and exerts its diverse physiological
      actions through multiple signaling pathways. Despite the role of the receptor
      system in a range of biological functions, the effects of NK3R activation on
      chromatin dynamics and gene expression have received limited attention. The
      present work determined the effects of senktide, a selective NK3R agonist, on
      chromatin organization, acetylation, and gene expression, using qRT-PCR, in a
      hypothalamic cell line (CLU 209) that expresses the NK3R. Senktide (1 nM, 10nM)
      caused a relaxation of chromatin, an increase in global acetylation of histone H3
      and H4, and an increase in the expression of a common set of genes involved in
      cell signaling, cell growth, and synaptic plasticity. Pretreatment with histone
      acetyltransferase (HAT) inhibitor (garcinol and 2-methylene y-butylactone), that
      inhibits p300, p300/CREB binding protein (CBP) associated factor (PCAF), and GCN
      5, prevented the senktide-induced increase in expression of most, but not all, of
      the genes upregulated in response to 1 nM and 10nM senktide. Treatment with 100
      nM had the opposite effect: a reduction in chromatin relaxation and decreased
      acetylation. The expression of four genes was significantly decreased and the HAT
      inhibitor had a limited effect in blocking the upregulation of genes in response
      to 100 nM senktide. Activation of the NK3R appears to recruit multiple pathways,
      including acetylation, and possibly histone deactylases, histone methylases, or
      DNA methylases to affect chromatin structure and gene expression.

PMID- 22985860
TI  - Differential gene expression between summer and winter diapause pupae of the
      onion maggot Delia antiqua, detected by suppressive subtractive hybridization.
AB  - To gain a better understanding of the molecular mechanisms regulating pupal
      diapause of the onion maggot Delia antiqua, PCR-based suppressive subtractive
      hybridization was performed to identify genes involved in summer and/or winter
      diapause. A total of 209 unique sequences were obtained including 89 in forward
      library for winter diapausing pupae and 120 in the reverse library for summer
      diapausing pupae. 76.4% (68/89) and 68.3% (82/120) unique sequences had
      significant hits to non-redundant proteins database. Gene functional annotation
      showed these non-redundant sequences are involved in stress response and innate
      immunity, metabolism and energy, information processing and regulation, binding,
      food storage, morphogenesis and development, cell skeleton and cycle, protein
      synthesis and folding. Approximately 28.2% (59/209) transcripts showed no
      significant similarity to any other sequence in the public databases, probably
      representing unique genes of the onion maggot. Semi-quantitative RT-PCR revealed
      that the relative expression levels of 18 genes were comparable between summer
      and winter diapause. This study elucidates the temporal expression of diapause
      related genes in onion maggot, also provides new insights into the differences in
      the physiological changes in summer and winter pupae. Functional characterization
      of some candidate genes will further enhance the understanding of the generating,
      maintaining, and breaking mechanism of diapause.

PMID- 22985861
TI  - Environmental control of trypsin secretion in the midgut of the two-spotted field
      cricket, Gryllus bimaculatus.
AB  - The two most important environmental factors controlling the release of trypsin
      in Gryllus bimaculatus are temperature and food consumption. Food consumption is
      in turn controlled by food availability (quantity), food quality (contained
      nutrients, inhibitors), developmental stage, age, sex and the daily light-dark
      cycle. The secretion of trypsin was higher at an acclimation temperature (AT) of
      22 degrees C than at 32 degrees C, although the weight of caecal tissue and body
      weight were lower. The trypsin secretion at both experimental temperatures (25
      degrees C and 35 degrees C) was almost 2 times greater in crickets maintained at
      22 degrees C AT since egg hatch than those maintained only since the last larval
      stage, but not at 32 degrees C AT. Acclimation became increasingly rotational
      with increased exposure time at different rearing temperatures. The more food
      consumed the higher the trypsin secretion. Secretion was highest on day 3 in
      adult females and day 2 in males, corresponding to the day of maximal food
      consumption. Secretion was less than 20% in starved or cellulose fed females
      compared to those fed a control diet. Food reached the caeca in starved crickets
      within 30min and induced an increased trypsin secretion. Crickets started feeding
      at the onset of darkness, and trypsin secretion was significantly elevated near
      the end of the scotophase. The in vivo response to 0.4% soybean trypsin inhibitor
      (SBTI) fed throughout the last larval stage resulted in reduced growth and a 50%
      decrease in trypsin secretion in 2day old adult females. An adaptation to the
      reduction of trypsin secretion occurred when G. bimaculatus was fed 0.1% and 0.2%
      SBTI, but not when fed with 0.4%.

PMID- 22985862
TI  - Evolutionary plasticity of insect immunity.
AB  - Many insect genomes have been sequenced and the innate immune responses of
      several species have been studied by transcriptomics, inviting the comparative
      analysis of immunity-related genes. Such studies have demonstrated significant
      evolutionary plasticity, with the emergence of novel proteins and protein domains
      correlated with insects adapting to both abiotic and biotic environmental
      stresses. This review article focuses on effector molecules such as antimicrobial
      peptides (AMPs) and proteinase inhibitors, which display greater evolutionary
      dynamism than conserved components such as immunity-related signaling molecules.
      There is increasing evidence to support an extended role for insect AMPs beyond
      defense against pathogens, including the management of beneficial endosymbionts.
      The total number of AMPs varies among insects with completed genome sequences,
      providing intriguing examples of immunity gene expansion and loss. This
      plasticity is discussed in the context of recent developments in evolutionary
      ecology suggesting that the maintenance and deployment of immune responses
      reallocates resources from other fitness-related traits thus requiring fitness
      trade-offs. Based on our recent studies using both model and non-model insects, I
      propose that insect immunity genes can be lost when alternative defense
      strategies with a lower fitness penalty have evolved, such as the so-called
      social immunity in bees, the chemical sanitation of the microenvironment by some
      beetles, and the release of antimicrobial secondary metabolites in the hemolymph.
      Conversely, recent studies provide evidence for the expansion and functional
      diversification of insect AMPs and proteinase inhibitors to reflect coevolution
      with a changing pathosphere and/or adaptations to habitats or food associated
      with microbial contamination.

PMID- 22985863
TI  - Sexual dimorphism, mating systems, and nuptial gifts in two Asian fireflies
      (Coleoptera: Lampyridae).
AB  - Many insect taxa show conspicuous sexual dimorphism in which females lack
      functional wings and are therefore incapable of flight. In fireflies, this loss
      of female flight is correlated with male production of spermatophore nuptial
      gifts, with species with flightless females also lacking gift production. In this
      study we further examined the relationship between sexual dimorphism and nuptial
      gifts by examining the reproductive ecology of two Asian fireflies, the sexually
      monomorphic Aquatica ficta (Luciolinae) and dimorphic Pyrocoelia pectoralis
      (Lampyrinae). We describe the reproductive anatomy of P. pectoralis males and
      females, and the time course of A. ficta spermatophore transfer. Through a series
      of mating experiments, we determined the effect of the number of matings on
      female fecundity, egg hatching success and female lifespan. The spermatophore
      producing A. ficta was found to be monandrous, and female lifespan doubled as a
      result of that single mating. P. pectoralis was found to lack spermatophores but
      females were polyandrous and fecundity and egg hatching success both increased
      with additional matings. These results contradict patterns known from North
      American firefly species and provide insight into the role of male-derived
      substances in mating systems.

PMID- 22985864
TI  - Genome-wide analysis of transcriptional changes in the thoracic muscle of the
      migratory locust, Locusta migratoria, exposed to hypobaric hypoxia.
AB  - Hypobaric hypoxia has both beneficial and detrimental effects on living organisms
      in high altitude regions. The impact of hypobaric hypoxia has been investigated
      in numerous vertebrates. However, it is still not well characterized how
      invertebrates respond to hypobaric hypoxia. In this study, we examined the
      transcriptional profiles of locust thoracic muscles using microarrays to disclose
      their strategies to cope with hypobaric hypoxia. We found that hypoxia-inducible
      factor (HIF) and its target genes did not respond significantly to hypobaric
      hypoxia. As with severe, normobaric hypoxia, mitochondrial activities were
      systemically suppressed, mainly involving in energy production and mitochondrial
      biogenesis. The surveillance processes, involving in clearance of dysfunctional
      proteins in endoplasmic reticulum, were activated, e.g. endoplasmic reticulum
      associated degradation, protein glycosylation, and protein folding. In contrast
      to severe, normobaric hypoxia, glycolysis was suppressed and the pentose
      phosphate pathway strengthened. Our data suggested that hypobaric hypoxia induced
      an oxidative stress rather than an energy crisis in locust thoracic muscles. Our
      research provides a different perspective of biological responses to hypoxia,
      complementing the well-studied biological responses to extreme, normobaric
      hypoxia.

PMID- 22985865
TI  - [Stroke in the very old: myths and realities].
AB  - BACKGROUND AND OBJECTIVE: The incidence of stroke in the very old is increasing.
      However, there are very few data regarding the differences in the management and
      outcomes in Spain. MATERIAL AND METHODS: We analyzed the clinical
      characteristics, diagnostic and therapeutic procedures, medical complications and
      intrahospitalary mortality in 463 subjects admitted because of ischemic stroke
      between 2009 and 2010. Very-old patients (>= 85 year-old) were compared with
      younger patients. RESULTS: Very old patients showed on admission higher frequency
      of atrial fibrillation (34 vs 19%, P>.001) and lower use of antiplatelet agents
      and oral anticoagulants (P<.001). Disability and stroke severity were higher
      among the very old (P<.001) and the use of diagnostic and therapeutic procedures
      was significantly lower (P<.001). The length of stay was longer in the very old
      (12 [6-24] days vs 8 [5-15], P<.001), as wells as the intrahospitalary mortality
      (27 vs 6%, P<.001). After a multivariate analysis, independent predictive factors
      of mortality were previous disability, measured by the modified Rankin scale (95%
      confidence interval [95%CI] 1.6-10.7), impaired level of consciousness (IC95% 2.1
      13.9) and stroke severity measured by the National Institutes of Health Stroke
      Scale (95%CI 1.8-38.1). CONCLUSIONS: Very old patients admitted with ischemic
      stroke undergo less diagnostic and therapeutic procedures. However, in our study,
      very old age was not an independent predictor of mortality, which was essentially
      determined by previous functional status and stroke severity.

PMID- 22985866
TI  - [Effectiveness of a perioperative chronic medication reconciliation program in
      patients scheduled for elective surgery].
AB  - BACKGROUND AND OBJECTIVE: Evaluation of the effectiveness of a perioperative
      medication reconciliation program in patients scheduled for elective surgery on
      perioperative medication management protocol adherence. MATERIAL AND METHODS:
      Ambispective cross-cohort study: prospective cohort (Group A), and retrospective
      control cohort (Group B) without intervention. Forty eight hours before admission
      a pharmacist generates a proposal on medication active prior to admission to be
      maintained/discontinued during the perioperative period according to the hospital
      protocols. The Pharmacy proposal is validated/modified by an anesthesiologist 24h
      before admission. At the time of admission, after checking with the patient the
      medication list, the nurse initiates scheduled medication administration pre and
      postoperatively. The indicator for program effectiveness assessment is the degree
      of compliance with perioperative medication management protocols at 24, 48 and
      72h of admission for intervention and control cohorts. RESULTS: Five hundred and
      three patients were included. One thousand two hundred and eleven pharmacy
      medication management recommendations were performed in Group A (intervention),
      of which 94.9% agreed with protocol. In Group B (control before program
      implementation) action taken by physicians agreed with protocol only in 32.4% of
      all cases. CONCLUSIONS: The medication reconciliation program significantly
      increased compliance with the recommendations on chronic medication perioperative
      management.

PMID- 22985867
TI  - [European Innovation Partnership on active and healthy ageing].

PMID- 22985868
TI  - [What blood pressure levels have more influence in the development of target
      organ damage in patients with resistant hypertension?].

PMID- 22985869
TI  - [Hypertriglyceridemic waist phenotype is a risk factor for subclinical
      atherosclerosis in human immunodeficiency virus-infected patients].
AB  - BACKGROUND AND OBJECTIVE: To study the association between hypertriglyceridemic
      waist phenotype and the presence of subclinical atherosclerosis in human
      immunodeficiency virus (HIV) infected patients. PATIENTS AND METHODS: Cross
      sectional study. Hypertriglyceridemic waist phenotype was considered if the waist
      was >=90cm and triglycerides >=2.0mmol/l (178mg/dl) in men and >=85cm and
      >=1.5mmol/L (133mg/dl) in women, respectively. We used the intima-media thickness
      (IMT) to detect carotid subclinical atherosclerosis. RESULTS: We analyzed 152
      patients, of whom 128 (84.2%) were receiving antiretroviral therapy, 40.7% were
      receiving protease inhibitors and 38.1% were treated with non-nucleoside reverse
      transcriptase inhibitors. The prevalence of hypertriglyceridemic waist phenotype
      was 23.6% (95% confidence interval [CI] 16.8-30.3%). Patients with
      hypertriglyceridemic waist phenotype had higher cardiovascular risk according to
      the Framingham score (11.09 [7.6] vs 3.88 [4], P=0.001) and lipodystrophy (33.3
      vs. 13.7%, P=0.032) and metabolic syndrome (69.4 vs. 1.9%, P<0.001) were more
      frequent. The IMT was elevated in 21 (13.8%) patients. Hypertriglyceridemic waist
      phenotype (odds ratio [OR] 4.66 [95%CI 1.05-20.6; P = 0.043]) and metabolic
      syndrome (OR 3.74 [95%CI 1.25-11.23; P = 0.018]) were independently associated
      with higher IMT. CONCLUSIONS: The hypertriglyceridemic waist phenotype is a risk
      factor for subclinical atherosclerosis in HIV infected patients and it is useful
      to detect patients with lipodystrophy, metabolic syndrome and high cardiovascular
      risk.

PMID- 22985870
TI  - Nasolabial aesthetics correlates poorly with skeletal symmetry in unilateral
      cleft lip and palate.
AB  - OBJECTIVE: To evaluate the correlation between symmetry of the craniofacial
      skeleton and aesthetics of the nose and upper lip in children with complete
      unilateral cleft lip and palate (CUCLP). MATERIAL AND METHODS: Craniofacial
      symmetry was evaluated on postero-anterior (PA) cephalograms of 54 children (37
      boys and 17 girls; mean age = 11.0 years, SD 1.6) with CUCLP repaired with a one
      stage closure (Cleft group). Treated subjects were age- and gender-matched with
      54 untreated subjects taken from the University of Michigan Growth Study (Control
      group). Fourteen coefficients of asymmetry (CAs) were calculated and four angles
      were measured. Four raters assessed the nasolabial appearance on cropped facial
      and profile photographs with the 5-grade aesthetic index of Asher-McDade (grade 1
      means the most aesthetic and grade 5 the least aesthetical outcome) in the Cleft
      group only. Independent t-tests were used to evaluate the inter-group differences
      for CAs. Pearson's correlation coefficients were calculated to examine a
      relationship between particular components of the aesthetical index and CAs.
      Multiple regression analyses were carried out to explain the nasolabial
      aesthetics on the basis of craniofacial symmetry. RESULTS: In the Cleft group,
      most cephalometric variables demonstrated asymmetry not exceeding 10%. The Cleft
      and Control groups differed regarding three angular measurements (Se, Ism, and
      ANS) and 1 CA (Mo-V). Three of the four nasolabial components demonstrated
      correlation with some cephalometric variables. However, the correlation
      coefficients were low (range: -0.309 to 0.305). CONCLUSIONS: There is a weak
      correlation between craniofacial skeletal symmetry and aesthetics of the nose and
      upper lip in children with CUCLP.

PMID- 22985871
TI  - Failure of plastic surgical clinical trials to document compliance with
      international ethical guidelines: a systematic review.
AB  - BACKGROUND: The Declaration of Helsinki (DOH) mandates that clinical trials must
      follow specific ethical standards including independent ethical review and
      registration in a public database to protect the rights and safety of human
      subjects and promote public trust. The purpose of this study was to perform a
      systematic review to identify whether independent ethical review and trial
      registration had been documented in all prospective clinical studies published in
      the journals Plastic and Reconstructive Surgery, Annals of Plastic Surgery and
      the Journal of Plastic Reconstructive and Aesthetic Surgery from 7/2007 to 7/2011
      and if there was any difference in documentation between journals and between
      types of studies. METHODS: The PubMed database was selected to search through the
      medical literature with specific inclusion criteria to disqualify irrelevant
      articles from the study. Appropriate articles were extracted, and all
      investigators assessed their quality and validity to maximize reproducibility.
      Each investigator systematically reviewed every article to determine whether
      independent ethical review and trial registration had been reported. Each
      investigator staged every study using the 2011 Oxford Centre for Evidence Based
      Medicine criteria. The data were then synthesized and analyzed for documentation
      of independent ethical review and trial registration. RESULTS: Of the 235 studies
      retrieved, 155 met our inclusion criteria as prospective studies, 102 reported
      independent ethical review. Eight studies reported trial registration in a public
      database, two additional studies were registered at clinicaltrials.gov, but the
      publications did not document their registration. Seven of the reported studies
      did not comply with the DOH as they had been registered retroactively; thus only
      one study out of 155 (<1%) documented compliance with the DOH. Using Fisher's
      exact test, the only statistically significant difference between the groups was
      better documentation in PRS level 2 studies than in PRS level 3 studies (p =
      0.007). CONCLUSION: Plastic surgery clinical trials' documentation of compliance
      with international ethical guidelines must improve.

PMID- 22985872
TI  - QAIT: a quality assurance issue tracking tool to facilitate the improvement of
      clinical data quality.
AB  - In clinical and translational research as well as clinical trial projects,
      clinical data collection is prone to errors such as missing data, and
      misinterpretation or inconsistency of the data. A good quality assurance (QA)
      program can resolve many such errors though this requires efficient
      communications between the QA staff and data collectors. Managing such
      communications is critical to resolving QA problems but imposes a major challenge
      for a project involving multiple clinical and data processing sites. We have
      developed a QA issue tracking (QAIT) system to support clinical data QA in the
      Clinical Breast Care Project (CBCP). This web-based application provides
      centralized management of QA issues with role-based access privileges. It has
      greatly facilitated the QA process and enhanced the overall quality of the CBCP
      clinical data. As a stand-alone system, QAIT can supplement any other clinical
      data management systems and can be adapted to support other projects.

PMID- 22985873
TI  - Identification enhancement of auditory evoked potentials in EEG by epoch
      concatenation and temporal decorrelation.
AB  - Event-related potentials (ERP) recorded by electroencephalography (EEG) are brain
      responses following an external stimulus, e.g., a sound or an image. They are
      used in fundamental cognitive research and neurological and psychiatric clinical
      research. ERPs are weaker than spontaneous brain activity and therefore it is
      difficult or even impossible to identify an ERP in the brain activity following
      an individual stimulus. For this reason, a blind source separation method relying
      on statistical information is proposed for the isolation of ERP after auditory
      stimulation. In this paper it is suggested to integrate epoch concatenation into
      the popular temporal decorrelation algorithm SOBI/TDSEP relying on time shifted
      correlations. With the proposed epoch concatenation temporal decorrelation (ecTD)
      algorithm a component representing the auditory evoked potential (AEP) is found
      in electroencephalographic data from an auditory stimulation experiment lasting
      3min. The ecTD result is compared with the averaged AEP and it is superior to the
      result from the SOBI/TDSEP algorithm. Furthermore the ecTD processing leads to
      significant increases in the signal-to-noise ratio (shape SNR) of the AEP and
      reduces the computation time by 50% if compared to the SOBI/TDSEP calculation. It
      can be concluded that data concatenation in combination with temporal
      decorrelation is useful for isolating and improving the properties of an AEP
      especially in a short duration stimulation experiment.

PMID- 22985874
TI  - Targeted delivery via avidin fusion protein: intracellular fate of biotinylated
      doxorubicin derivative and cellular uptake kinetics and biodistribution of
      biotinylated liposomes.
AB  - In this study, avidin-biotin technology was combined with a multifunctional drug
      carrier modality i.e. liposomes to achieve an active and versatile targeting
      approach. The anti-cancer drug doxorubicin (DOX) was modified with direct
      biotinylation (B-DOX) (Allart et al., 2003), or encapsulated in biotinylated
      sterically stabilized pH-sensitive liposomes (BL-DOX), and targeted to the
      lentiviral vector transduced cells expressing an avidin fusion protein on the
      cell membrane (Lehtolainen et al., 2003; Lesch et al., 2009). The direct
      biotinylation of doxorubicin improved cell internalization in rat glioma (BT4C)
      cells expressing avidin fusion protein receptor but cell toxicity was reduced by
      78-fold due to impaired nuclear localization. In contrast, liposomal formulations
      restored the biological activity of the DOX in several cell lines. However,
      mainly due to uptake via non-specific pathways the active targeting of BL-DOX was
      negligible in both in vitro and in vivo studies. Active targeting with
      multifunctional drug carrier systems is challenging and further studies will be
      needed to optimize the properties of targeted drug carrier and receptor
      expression systems.

PMID- 22985875
TI  - Topical treatment with anti-oxidants and Au nanoparticles promote healing of
      diabetic wound through receptor for advance glycation end-products.
AB  - Impairment in diabetic wound healing constitutes an enormous biomedical burden.
      The receptor for advanced glycation end-products (RAGE) expression in the
      diabetic cutaneous wound may play a key role. However, the relationship between
      RAGE expression and topical application of anti-oxidant agents with gold
      nanoparticles (AuNP) in cutaneous diabetic wounds remains unclear. We tested the
      3-5 nm AuNP, epigallocatechin gallate (EGCG), and alpha-lipoic acid (ALA) could
      change the RAGE expression and be helpful in diabetic wound. The mixture of
      AuNP+EGCG+ALA (AuEA) significantly attenuated the AGE-induced RAGE protein
      expression in fibroblasts (Hs68). Topical EGCG+ALA (EA) and AuEA application
      accelerated wound healing on diabetic mouse skin and decreased the RAGE
      expression. Vascular endothelial growth factor but not angiopoietin-1
      significantly increased after EA or AuEA treatment for 7 days. Angiopoietin-2
      significantly decreased at day 7 in AuEA group. Furthermore, immunoblotting of
      diabetic wound tissue showed significant decrease of CD68 expression from day 3
      to day 7. The results suggest that combination of AuNP, EGCG, and ALA
      significantly accelerated diabetic cutaneous wound healing through angiogenesis
      regulation and anti-inflammatory effects. Blockade of RAGE by anti-oxidant agents
      and nanoparticles may restore effective wound healing in diabetic ulcer.

PMID- 22985876
TI  - Comparison of the efficacy and skin permeability of topical NSAID preparations
      used in Europe.
AB  - This study compared the efficacy and skin permeability of nine topical
      preparations of nonsteroidal anti-inflammatory drugs (NSAIDs) (ketoprofen,
      diclofenac, flurbiprofen, and piroxicam patches; and ketoprofen, diclofenac,
      piroxicam, niflumic acid, and ibuprofen gels) available in the European Union.
      The anti-inflammatory effect of these NSAID preparations was evaluated in rat
      models of acute inflammation (carrageenan or yeast treatment) and chronic
      inflammation (collagen or adjuvant treatment). Skin permeability of the
      preparations was evaluated in vitro using mouse skin. In rats with acute
      inflammation, both ketoprofen preparations significantly inhibited carrageenan
      induced edema and yeast-induced hyperalgesia. Flurbiprofen and diclofenac
      preparations also showed a significant anti-inflammatory effect, but the
      ketoprofen products were the most potent among the four patch preparations and
      five gel preparations. With repeated application, the ketoprofen patch
      significantly decreased edema from day 3 in collagen-treated rats, while other
      preparations (ketoprofen gel, diclofenac patch, and diclofenac gel) decreased
      edema from day 7. In rats with adjuvant-induced arthritis, only the ketoprofen
      patch significantly decreased edema after 2 weeks of application. In the skin
      permeation study, the ketoprofen preparations showed higher skin permeability
      compared with the other NSAID preparations. These results suggested that
      ketoprofen preparations had the most potent anti-inflammatory and analgesic
      activity related to good skin permeability. Efficacy of the ketoprofen patch was
      comparable to or better than that of ketoprofen gel at a lower dose and frequency
      of administration. Ketoprofen products, especially the patch preparation, could
      be useful for treating inflammatory pain in diseases like osteoarthritis and
      rheumatoid arthritis.

PMID- 22985877
TI  - Epitope of titin A-band-specific monoclonal antibody Tit1 5 H1.1 is highly
      conserved in several Fn3 domains of the titin molecule. Centriole staining in
      human, mouse and zebrafish cells.
AB  - BACKGROUND: Previously we have reported on the development of a new mouse anti
      titin monoclonal antibody, named MAb Titl 5 H1.1, using the synthetic peptide N
      AVNKYGIGEPLESDSVVAK-C which corresponds to an amino acid sequence in the A-region
      of the titin molecule as immunogen. In the human skeletal muscles, MAb Titl 5
      H1.1 reacts specifically with titin in the A-band of the sarcomere and in
      different non-muscle cell types with nucleus and cytoplasm, including centrioles.
      In this report we have studied the evolutionary aspects of the binding of MAb
      Tit1 5 H1.1 with its target antigen (titin). RESULTS: We have specified the
      epitope area of MAb Tit1 5 H1.1 by subpeptide mapping to the hexapeptide N-AVNKYG
      C. According to protein databases this amino acid sequence is located in the COOH
      terminus of several different Fn3 domains of the A-region of titin molecule in
      many organisms, such as human being, mouse, rabbit, zebrafish (Danio rerio), and
      even in sea squirt (Ciona intestinalis). Our immunohisto- and cytochemical
      studies with MAb Tit1 5 H1.1 in human, mouse and zebrafish tissues and cell
      cultures showed a striated staining pattern in muscle cells and also staining of
      centrioles, cytoplasm and nuclei in non-muscle cells. CONCLUSIONS: The data
      confirm that titin can play, in addition to the known roles in striated muscle
      cells also an important role in non-muscle cells as a centriole associated
      protein. This phenomenon is highly conserved in the evolution and is related to
      Fn3 domains of the titin molecule. Using titin A-band-specific monoclonal
      antibody MAb Tit1 5 H1.1 it was possible to locate titin in the sarcomeres of
      skeletal muscle cells and in the centrioles, cytoplasm and nuclei of non-muscle
      cells in phylogenetically so distant organisms as Homo sapiens, Mus musculus and
      zebrafish (Danio rerio).

PMID- 22985878
TI  - Comparative in vitro and in vivo efficacies of human simulated doses of
      ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa.
AB  - The combination of ceftazidime and avibactam possesses potent activity against
      resistant Gram-negative pathogens, including Pseudomonas aeruginosa. We compared
      the efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam
      using a hollow-fiber system and neutropenic and immunocompetent murine thigh
      infection models. Twenty-seven clinical P. aeruginosa isolates with ceftazidime
      MICs of 8 to 128 mg/liter and ceftazidime-avibactam MICs of 4 to 32 mg/liter were
      utilized in neutropenic mouse studies; 15 of the isolates were also evaluated in
      immunocompetent mice. Six isolates were studied in both the hollow-fiber system
      and the neutropenic mouse. In both systems, the free drug concentration-time
      profile seen in humans given 2 g of ceftazidime every 8 h (2-h infusion), with or
      without avibactam at 500 mg every 8 h (2-h infusion), was evaluated. In vivo
      activity was pharmacodynamically predictable based on the MIC. Ceftazidime
      decreased bacterial densities by >=0.5 log unit for 10/27 isolates, while
      ceftazidime-avibactam did so for 22/27 isolates. In immunocompetent animals,
      enhancements in activity were seen for both drugs, with ceftazidime achieving
      reductions of >=0.3 log unit for 10/15 isolates, whereas ceftazidime-avibactam
      did so against all 15 isolates. In vitro, ceftazidime resulted in regrowth by 24
      h against all isolates, while ceftazidime-avibactam achieved stasis or better
      against 4/7 isolates. Mutants with elevated ceftazidime-avibactam MICs appeared
      after 24 h from 3/7 isolates studied in vitro; however, no resistant mutants were
      detected in vivo. Against this highly ceftazidime-nonsusceptible population of P.
      aeruginosa, treatment with human simulated doses of ceftazidime-avibactam
      resulted in pharmacodynamically predictable activity, particularly in vivo,
      against isolates with MICs of <=16 mg/liter, and this represents a potential new
      option to combat these difficult-to-treat pathogens.

PMID- 22985880
TI  - Efficacy of ceftaroline fosamil in a staphylococcal murine pneumonia model.
AB  - Ceftaroline fosamil is a cephalosporin with activity against Gram-positive
      pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The
      objective of this study was to characterize the dose-response relationship of
      ceftaroline fosamil against S. aureus in an immunocompromised murine pneumonia
      model, as well as to evaluate the efficacy of the humanized regimen of 600 mg
      intravenously (i.v.) every 12 h. Seventeen S. aureus (2 methicillin-susceptible
      Staphylococcus aureus [MSSA], 15 MRSA) isolates with ceftaroline MICs of 0.5 to 4
      MUg/ml were utilized. The pharmacokinetics of ceftaroline in serum and epithelial
      lining fluid (ELF) were evaluated to determine bronchopulmonary exposure profiles
      in infected and uninfected animals, using single and human-simulated doses. Serum
      fT>MIC (the percentage of time that free drug concentrations remain above the
      MIC) of 17% to 43% was required to produce a 1-log(10) kill in the dose-ranging
      studies. These targets were readily achieved with the humanized exposure profile,
      where decreases of 0.64 to 1.95 log(10) CFU were observed against 13 MRSA and
      both MSSA isolates tested. When taken as a composite, the fT>MICs required for
      stasis and a 1-log(10) kill were 16% and 41%, respectively. ELF concentrations
      were similar to serum concentrations across the dosing interval in infected and
      uninfected animals. The serum fT>MIC targets required in this lung infection
      model were similar to those observed with ceftaroline against S. aureus in a
      murine thigh infection model. Exposures simulating the human dose of 600 mg i.v.
      every 12 h achieved pharmacodynamic targets against MRSA and MSSA considered
      susceptible by current U.S. FDA breakpoints.

PMID- 22985879
TI  - Evaluation of single and combination therapies with tenofovir disoproxil fumarate
      and emtricitabine in vitro and in a robust mouse model supporting high levels of
      hepatitis B virus replication.
AB  - Next-generation therapies for chronic hepatitis B virus (HBV) infection will
      involve combinations of established and/or experimental drugs. The current study
      investigated the in vitro and in vivo efficacy of tenofovir disoproxil fumarate
      (TDF) and/or emtricitabine [(-)-FTC] alone and in combination therapy for HBV
      infection utilizing the HepAD38 system (human hepatoblastoma cells transfected
      with HBV). Cellular pharmacology studies demonstrated increased levels of (-)-FTC
      triphosphate with coincubation of increasing concentrations of TDF, while (-)-FTC
      had no effect on intracellular tenofovir (TFV) diphosphate levels. Quantification
      of extracellular HBV by real-time PCR from hepatocytes demonstrated the anti-HBV
      activity with TDF, (-)-FTC, and their combination. Combination of (-)-FTC with
      TDF or TFV (ratio, 1:1) had a weighted average combination index of 0.7 for both
      combination sets, indicating synergistic antiviral effects. No cytotoxic effects
      were observed with any regimens. Using an in vivo murine model which develops
      robust HBV viremia in nude mice subcutaneously injected with HepAD38 cells, TDF
      (33 to 300 mg/kg of body weight/day) suppressed virus replication for up to 10
      days posttreatment. At 300 mg/kg/day, (-)-FTC strongly suppressed virus titers to
      up to 14 days posttreatment. Combination therapy (33 mg/kg/day each drug)
      sustained suppression of virus titer/ml serum (<1 log(10) unit from pretreatment
      levels) at 14 days posttreatment, while single-drug treatments yielded virus
      titers 1.5 to 2 log units above the initial virus titers. There was no difference
      in mean alanine aminotransferase values or mean wet tumor weights for any of the
      groups, suggesting a lack of drug toxicity. TDF-(-)-FTC combination therapy
      provides more effective HBV suppression than therapy with each drug alone.

PMID- 22985881
TI  - Bacterial resistance to antisense peptide phosphorodiamidate morpholino
      oligomers.
AB  - Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics
      that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)(3)RXB-AcpP
      (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is beta
      alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the
      essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)(3)RXB
      AcpP was 2.5 MUM (14 MUg/ml) in Escherichia coli W3110. The rate of spontaneous
      resistance of E. coli to (RFF)(3)RXB-AcpP was 4 * 10(-7) mutations/cell division.
      A spontaneous (RFF)(3)RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC
      of (RFF)(3)RXB-AcpP was 40 MUM (224 MUg/ml) for PR200.1. The MICs of standard
      antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was
      identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs
      conjugated to (RFF)(3)RXB or peptides with a similar composition or pattern of
      cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a
      mutation in sbmA, which encodes an active transport protein. In separate
      experiments, a (RFF)(3)RXB-AcpP-resistant isolate (RR3) was selected from a
      transposome library, and the insertion was mapped to sbmA. Genetic
      complementation of PR200.1 or RR3 with sbmA restored susceptibility to
      (RFF)(3)RXB-AcpP. Deletion of sbmA caused resistance to (RFF)(3)RXB-AcpP. We
      conclude that resistance to (RFF)(3)RXB-AcpP was linked to the peptide and not
      the phosphorodiamidate morpholino oligomer, dependent on the composition or
      repeating pattern of amino acids, and caused by mutations in sbmA. The data
      further suggest that (RFF)(3)R-XB PPMOs may be transported across the plasma
      membrane by SbmA.

PMID- 22985882
TI  - Rapid identification of international multidrug-resistant Pseudomonas aeruginosa
      clones by multiple-locus variable number of tandem repeats analysis and
      investigation of their susceptibility to lytic bacteriophages.
AB  - The objective of this study was to determine the genetic diversity of multidrug
      resistant (MDR) Pseudomonas aeruginosa strains isolated over a period of 12
      months in two French hospitals and to test their susceptibility to
      bacteriophages. A total of 47 MDR isolates recovered from hospitalized patients
      were genotyped using multiple-locus variable number of tandem repeats analysis.
      The genotypes were distributed into five clones (including 19, 5, 5, 3, and 3
      isolates, respectively) and 12 singletons. Comparison to 77 MDR strains from
      three other countries, and MLST analysis of selected isolates showed the
      predominance of international MDR clones. The larger clone, CC235, contained 59
      isolates displaying different antibiotic resistance mechanisms, including the
      presence of the GES1, VIM-2, VIM-4, and IMP-1 beta-lactamases. Three newly
      isolated P. aeruginosa bacteriophages were found to lyse 42 of the 44 analyzed
      strains, distributed into the different clonal complexes. This pilot study
      suggests that systematic genotyping of P. aeruginosa MDR strains could improve
      our epidemiological understanding of transmission at both the local (hospital)
      and the national level and that phage therapy could be an alternative or a
      complementary treatment to antibiotics for treating MDR-infected patients.

PMID- 22985883
TI  - Influence of the protein kinase C activator phorbol myristate acetate on the
      intracellular activity of antibiotics against hemin- and menadione-auxotrophic
      small-colony variant mutants of Staphylococcus aureus and their wild-type
      parental strain in human THP-1 cells.
AB  - In a previous study (L. G. Garcia et al., Antimicrob. Agents Chemother. 56:3700
      3711, 2012), we evaluated the intracellular fate of menD and hemB mutants
      (corresponding to menadione- and hemin-dependent small-colony variants,
      respectively) of the parental COL methicillin-resistant Staphylococcus aureus
      strain and the pharmacodynamic profile of the intracellular activity of a series
      of antibiotics in human THP-1 monocytes. We have now examined the phagocytosis
      and intracellular persistence of the same strains in THP-1 cells activated by
      phorbol 12-myristate 13-acetate (PMA) and measured the intracellular activity of
      gentamicin, moxifloxacin, and oritavancin in these cells. Postphagocytosis
      intracellular counts and intracellular survival were lower in PMA-activated
      cells, probably due to their higher killing capacities. Gentamicin and
      moxifloxacin showed a 5- to 7-fold higher potency (lower static concentrations)
      against the parental strain, its hemB mutant, and the genetically complemented
      strain in PMA-activated cells and against the menD strain in both activated and
      nonactivated cells. This effect was inhibited when cells were incubated with N
      acetylcysteine (a scavenger of oxidant species). In parallel, we observed that
      the MICs of these drugs were markedly reduced if bacteria had been preexposed to
      H(2)O(2). In contrast, the intracellular potency of oritavancin was not different
      in activated and nonactivated cells and was not decreased by the addition of N
      acetylcysteine, regardless of the phenotype of the strains. The oritavancin MIC
      was also unaffected by preincubation of the bacteria with H(2)O(2). Thus,
      activation of THP-1 cells by PMA may increase the intracellular potency of
      certain antibiotics (probably due to synergy with reactive oxygen species), but
      this effect cannot be generalized to all antibiotics.

PMID- 22985884
TI  - beta-Lactams increase the antibacterial activity of daptomycin against clinical
      methicillin-resistant Staphylococcus aureus strains and prevent selection of
      daptomycin-resistant derivatives.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged to be one of the
      most important pathogens both in health care and in community-onset infections.
      Daptomycin (DAP) is a cyclic anionic lipopeptide recommended for treatment of
      skin infections, bacteremia, and right-sided endocarditis caused by MRSA.
      Resistance to DAP (DAP(r)) has been reported in MRSA and is mostly accompanied by
      a parallel decrease in oxacillin resistance, a process known as the "seesaw
      effect." Our study provides evidence that the seesaw effect applies to other beta
      lactams and carbapenems of clinical use, including nafcillin (NAF), cefotaxime
      (CTX), amoxicillin-clavulanic (AMC), and imipenem (IMP), in heterogeneous DAP(r)
      MRSA strains but not in MRSA strains expressing homogeneous beta-lactam
      resistance. The antibacterial efficacy of DAP in combination with beta-lactams
      was evaluated in isogenic DAP-susceptible (DAP(s))/Dap(r) MRSA strains originally
      obtained from patients that failed DAP monotherapy. Both in vitro (MIC, synergy
      kill curve) and in vivo (wax worm model) approaches were used. In these models,
      DAP and a beta-lactam proved to be highly synergistic against both heterogeneous
      and homogeneous clinical DAP(r) MRSA strains. Mechanistically, beta-lactams
      induced a reduction in the cell net positive surface charge, reverting the
      increased repulsion provoked by DAP alone, an effect that may favor the binding
      of DAP to the cell surface. The ease of in vitro mutant selection was observed
      when DAP(s) MRSA strains were exposed to DAP. Importantly, the combination of DAP
      and a beta-lactam prevented the selection of DAP(r) variants. In summary, our
      data show that the DAP-beta-lactam combination may significantly enhance both the
      in vitro and in vivo efficacy of anti-MRSA therapeutic options against DAP(r)
      MRSA infections and represent an option in preventing DAP(r) selection in
      persistent or refractory MRSA infections.

PMID- 22985885
TI  - Novel antibiofilm chemotherapy targets exopolysaccharide synthesis and stress
      tolerance in Streptococcus mutans to modulate virulence expression in vivo.
AB  - Fluoride is the mainstay of dental caries prevention, and yet current
      applications offer incomplete protection and may not effectively address the
      infectious character of the disease. Therefore, we evaluated the effectiveness of
      a novel combination therapy (CT; 2 mM myricetin, 4 mM tt-farnesol, 250 ppm of
      fluoride) that supplements fluoride with naturally occurring, food-derived,
      antibiofilm compounds. Treatment regimens simulating those experienced clinically
      (twice daily for <=60 s) were used both in vitro over a saliva-coated
      hydroxyapatite biofilm model and in vivo with a rodent model of dental caries.
      The effectiveness of CT was evaluated based on the incidence and severity of
      carious lesions (compared to fluoride or vehicle control). We found that CT was
      superior to fluoride (positive control, P < 0.05); topical applications
      dramatically reduced caries development in Sprague-Dawley rats, all without
      altering the Streptococcus mutans or total populations within the plaque. We
      subsequently identified the underlying mechanisms through which applications of
      CT modulate biofilm virulence. CT targets expression of key Streptococcus mutans
      genes during biofilm formation in vitro and in vivo. These are associated with
      exopolysaccharide matrix synthesis (gtfB) and the ability to tolerate exogenous
      stress (e.g., sloA), which are essential for cariogenic biofilm assembly. We also
      identified a unique gene (SMU.940) that was severely repressed and may represent
      a potentially novel target; its inactivation disrupted exopolysaccharide
      accumulation and matrix development. Altogether, CT may be clinically more
      effective than current anticaries modalities, targeting expression of bacterial
      virulence associated with pathogenesis of the disease. These observations may
      have relevance for development of enhanced therapies against other biofilm
      dependent infections.

PMID- 22985887
TI  - Effect of continuous venovenous hemofiltration dose on achievement of adequate
      vancomycin trough concentrations.
AB  - The vancomycin dose necessary for the achievement of target serum trough
      concentrations during continuous venovenous hemofiltration (CVVH) remains to be
      elucidated. This was a retrospective cohort study of critically ill adults at a
      tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010
      with a steady-state vancomycin trough concentration. The 87 included patients
      were grouped according to low (<=30 ml/kg/h; n = 10) or high (>30 ml/kg/h; n =
      77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough
      achievement occurred in only 32 (37%) patients. The primary endpoint of trough
      attainment significantly differed between HFR subgroups: 90% versus 30% in low-
      and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic
      trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h
      (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in
      those who achieved the trough goal. Irrespective of goal trough, an inverse
      correlation existed between HFR and serum vancomycin concentration (r = -0.423; P
      < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus
      (MRSA) patients, trough achievement was similar to the aggregate cohort (36%).
      Mortality at 28 days was unrelated to trough achievement in both the overall
      sample (P = 0.516) and in culture-positive MRSA patients (P = 0.396). Critically
      ill patients undergoing CVVH therapy may experience clinically significant
      reductions in goal vancomycin troughs. The results of the present study justify
      prospective evaluations in this population to determine the optimal vancomycin
      dosing strategy for attainment of goal trough concentrations.

PMID- 22985888
TI  - Vitamin D3 and insulin combined treatment promotes titanium implant
      osseointegration in diabetes mellitus rats.
AB  - This study investigated the effect of insulin and vitamin D(3) (VD(3)) treatment
      on implant osseointegration in diabetic mellitus (DM) rats. DM was induced by
      administration of streptozotocin in rats, which received implants insertion in
      the femur. Then animals were subjected to different treatment and divided to the
      following group: control, diabetic, insulin-treated diabetic, VD(3)-treated
      diabetic, insulin and VD(3) combination-treated diabetic rats. The glucose levels
      and weight of rats were periodically evaluated, and serum 25(OH)D(3) levels in
      rats were measured at the end of the experiment. Animals were sacrificed at 12
      weeks after surgery, the peri-implant trabecular microstructure, implant fixation
      and implant osseointegration were measured by microscopic computerized tomography
      (micro-CT) evaluation, push-out test and histomorphometric analysis. Diabetic
      rats displayed significantly higher blood glucose level, lower body weight, lower
      serum 25(OH)D(3) levels, and less implant osseointegration than controls. Insulin
      treatment showed restorative effect on body weight and serum 25(OH)D(3) levels of
      diabetic rats, but the blood glucose level in diabetic rats were still
      substantially higher compared to controls after 14 days therapy of insulin.
      Combined treatment restored hyperglycemia in diabetic rats to be normal, and
      reversed the impaired osseointegration capacity of implants, with the bone volume
      ratio and percent osseointegration increased by 1.37-fold and 1.6-fold in micro
      CT evaluation, the maximal push-out force and ultimate shear strength by 1.3-fold
      and 2.1-fold in push-out test, and the bone-to-implant contact and bone area
      ratio increased by 2.57-fold and 1.44-fold in histomorphometric analysis.
      Monotreatment also enhanced implant fixation, but less. These results indicated
      that insulin and VD(3) combined treatment may be an effective approach to enhance
      implant fixation in diabetic rats, but whether the results could be extrapolated
      to human needs further study.

PMID- 22985886
TI  - Genetic and biochemical characterization of an acquired subgroup B3 metallo-beta
      lactamase gene, blaAIM-1, and its unique genetic context in Pseudomonas
      aeruginosa from Australia.
AB  - Three clinical Pseudomonas aeruginosa isolates (WCH2677, WCH2813, and WCH2837)
      isolated from the Women's and Children's Hospital, Adelaide, Australia, produced
      a metallo-beta-lactamase (MBL)-positive Etest result. All isolates were PCR
      negative for known MBL genes. A gene bank was created, and an MBL gene,
      designated bla(AIM-1), was cloned and fully characterized. The encoded enzyme,
      AIM-1, is a group B3 MBL that has the highest level of identity to THIN-B and L1.
      It is chromosomal and flanked by two copies (one intact and one truncated) of an
      ISCR element, ISCR15. Southern hybridization studies indicated the movement of
      both ISCR15 and bla(AIM-1) within the three different clinical isolates. AIM-1
      hydrolyzes most beta-lactams, with the exception of aztreonam and, to a lesser
      extent, ceftazidime; however, it possesses significantly higher k(cat) values for
      cefepime and carbapenems than most other MBLs. AIM-1 was the first mobile group
      B3 enzyme detected and signals further problems for already beleaguered
      antimicrobial regimes to treat serious P. aeruginosa and other Gram-negative
      infections.

PMID- 22985889
TI  - Strain-adaptive in silico modeling of bone adaptation--a computer simulation
      validated by in vivo micro-computed tomography data.
AB  - Computational models are an invaluable tool to test different mechanobiological
      theories and, if validated properly, for predicting changes in individuals over
      time. Concise validation of in silico models, however, has been a bottleneck in
      the past due to a lack of appropriate reference data. Here, we present a strain
      adaptive in silico algorithm which is validated by means of experimental in vivo
      loading data as well as by an in vivo ovariectomy experiment in the mouse. The
      maximum prediction error following four weeks of loading resulted in 2.4% in bone
      volume fraction (BV/TV) and 8.4% in other bone structural parameters. Bone
      formation and resorption rate did not differ significantly between experiment and
      simulation. The spatial distribution of formation and resorption sites matched in
      55.4% of the surface voxels. Bone loss was simulated with a maximum prediction
      error of 12.1% in BV/TV and other bone morphometric indices, including a
      saturation level after a few weeks. Dynamic rates were more difficult to be
      accurately predicted, showing evidence for significant differences between
      simulation and experiment (p<0.05). The spatial agreement still amounted to
      47.6%. In conclusion, we propose a computational model which was validated by
      means of experimental in vivo data. The predictive value of an in silico model
      may become of major importance if the computational model should be applied in
      clinical settings to predict bone changes due to disease and test the efficacy of
      potential pharmacological interventions.

PMID- 22985890
TI  - Osteoblast migration into type I collagen gel and differentiation to osteocyte
      like cells within a self-produced mineralized matrix: a novel system for
      analyzing differentiation from osteoblast to osteocyte.
AB  - Osteoblasts are believed to differentiate into osteocytes, becoming embedded in
      bone, or to undergo apoptosis after the bone formation phase. The regulation of
      this terminal differentiation seems to be critical for bone homeostasis. However
      the mechanism remains unclear and there is no assay system currently available to
      analyze this process. To address this issue, we developed a new model in which
      osteoblasts are cultured on a type I collagen gel layer with osteogenic
      supplements beta-glycerophosphate and ascorbic acid. Cellular behavior was
      analyzed by electron microscopy, immunohistochemistry and real-time RT-PCR.
      Osteoblasts gradually migrated into the gel, produced collagen fibrils, and
      differentiated to osteocytic cells with bone lacunae- and canaliculi-like
      mineralization. Osteocalcin, DMP-1 and SOST protein expression was mainly
      expressed in the migrated cells within the mid-layer of the gel. Osteoblastic
      (ALP and osteocalcin) and osteocytic (PHEX, DMP-1 and SOST) mRNA expression was
      significantly increased compared with those of the cells cultured on plastic
      dishes alone after 21 days. The number of TUNEL-positive apoptotic cells
      gradually increased, reaching a maximum at 28 days. The cells were distributed at
      the surface and in the mid-layer of the gel at 7 days and after 14 days of
      culture, respectively. These data indicate that our model reproduces transition
      from osteoblasts to osteocytes, suggesting the following: 1) migration of
      osteoblasts into collagen gel may play a critical role in osteocytic
      differentiation; and 2) spatiotemporal gene expression and apoptosis may be
      involved in the terminal differentiation of osteoblasts. Our model will make it
      possible to study the mechanism of transition from osteoblast to osteocyte, and
      both cell type-related diseases including osteoporosis and osteonecrosis.

PMID- 22985891
TI  - A nonlinear QCT-based finite element model validation study for the human femur
      tested in two configurations in vitro.
AB  - PURPOSE: Femoral fracture is a common medical problem in osteoporotic
      individuals. Bone mineral density (BMD) is the gold standard measure to evaluate
      fracture risk in vivo. Quantitative computed tomography (QCT)-based homogenized
      voxel finite element (hvFE) models have been proved to be more accurate
      predictors of femoral strength than BMD by adding geometrical and material
      properties. The aim of this study was to evaluate the ability of hvFE models in
      predicting femoral stiffness, strength and failure location for a large number of
      pairs of human femora tested in two different loading scenarios. METHODS: Thirty
      six pairs of femora were scanned with QCT and total proximal BMD and BMC were
      evaluated. For each pair, one femur was positioned in one-legged stance
      configuration (STANCE) and the other in a sideways configuration (SIDE).
      Nonlinear hvFE models were generated from QCT images by reproducing the same
      loading configurations imposed in the experiments. For experiments and models,
      the structural properties (stiffness and ultimate load), the failure location and
      the motion of the femoral head were computed and compared. RESULTS: In both
      configurations, hvFE models predicted both stiffness (R(2)=0.82 for STANCE and
      R(2)=0.74 for SIDE) and femoral ultimate load (R(2)=0.80 for STANCE and R(2)=0.85
      for SIDE) better than BMD and BMC. Moreover, the models predicted qualitatively
      well the failure location (66% of cases) and the motion of the femoral head.
      CONCLUSIONS: The subject specific QCT-based nonlinear hvFE model cannot only
      predict femoral apparent mechanical properties better than densitometric
      measures, but can additionally provide useful qualitative information about
      failure location.

PMID- 22985892
TI  - Bone structure and geometry in young men: the influence of smoking, alcohol
      intake and physical activity.
AB  - BACKGROUND: The development of osteoporosis is influenced by peak bone mass
      attained in youth - the influence of lifestyle factors upon which is poorly
      described, especially amongst males. We sought to address this issue in a large
      scale study. METHODS: Hip bone mineral density (dual X-ray absorptiometry, DXA),
      bone microarchitecture (calcaneal quantitative ultrasound, QUS) and femoral
      geometry (magnetic resonance imaging, MRI) were characterised in 723 healthy male
      military recruits (mean +/- S.E. age 19.92 +/- 0.09 years [range 16-18 years],
      height 177.67 +/- 0.24 cm, weight 73.17 +/- 0.37 kg) on entry to UK Army
      training. Association was sought with prior physical activity, smoking status and
      alcohol intake. RESULTS: DXA measures were made in 651, MRI measures in 650, and
      QUS measures in 572 recruits. Increasing levels of weight-bearing physical
      activity enhanced periostial bone apposition, increases in both total hip and
      femoral neck bone mineral density (BMD; p <= 0.0001 in both cases), and cortical
      [p<0.0001] and periostial bone volumes [p=0.016]. Smoking habit was associated
      with preserved bone geometry, but worse BMD [p=0.0001] and QUS characteristics [p
      <= 0.0005]. Moderate alcohol consumption was associated with greater BMD [p <=
      0.015]. CONCLUSIONS: Whilst exercise (and perhaps moderate alcohol intake) is
      beneficial to bone morphometry, smoking is detrimental to bone mineral density in
      young males notable for the likely short duration of smoking to influence
      skeletal properties. However, differences in socio-economic status, lifestyle and
      related environmental factors may to some extent confound our results.

PMID- 22985893
TI  - MAP kinase kinase 1 (MKK1) is essential for transmission of Trypanosoma brucei by
      Glossina morsitans.
AB  - MAP kinase kinase 1 (MKK1) is encoded by a single copy gene in Trypanosoma
      brucei. It has been shown recently that MKK1 is not essential for bloodstream
      forms [14]. To investigate the requirement for MKK1 in other life-cycle stages we
      generated null mutants in procyclic forms of a fly-transmissible strain. These
      grew normally in culture and were able to establish midgut infections in tsetse
      at normal rates and intensities, but were incapable of colonising the salivary
      glands. Transformation of null mutants with an ectopic copy of MKK1 enabled
      parasites to complete the life cycle in tsetse and infect mice. This is the first
      example of a gene that is indispensable for transmission of T. brucei. It also
      raises the possibility that activating the MKK1 signalling cascade in vitro might
      trigger the differentiation and proliferation of life-cycle stages of T. brucei
      that are currently refractory to culture.

PMID- 22985894
TI  - Ethical and clinical responsibilities of dentists.

PMID- 22985895
TI  - Neuropathic orofacial pain patients in need of dental care.
AB  - Dental pain is a common complaint among the general population. Most pain is a
      result of traumatic injury or bacterial infection in pulpal and periapical
      tissues, and dental practitioners are successful at diagnosing these conditions
      and providing prompt relief. However, in some cases, patients continue to
      complain of persistent pain, which may be categorized as neuropathic. These
      people may avoid or neglect routine dental treatment or interventions to prevent
      precipitation, perpetuation or exacerbation of their pain condition, and
      practitioners may have to modify their procedures when managing the dental needs
      of this unique population.

PMID- 22985896
TI  - Influence of irrigating solution on postoperative pain following single-visit
      endodontic treatment: randomized clinical trial.
AB  - OBJECTIVE: To compare 2 irrigation solutions in terms of postoperative pain after
      single-visit treatment of chronic apical periodontitis with pulp necrosis.
      METHODS: A total of 126 patients requiring treatment of apical periodontitis and
      pulp necrosis were randomly assigned to 2 groups according to the solution used
      for irrigation: 5.25% sodium hypochlorite (NaOCl) or 2% chlorhexidine gel (CLX)
      (63 patients in each group). To assess postoperative pain, a questionnaire and
      pain intensity scale were administered at 24, 48 and 72 hours and 7 days after
      the procedure. The chi2 test was used to compare the intensity of pain with the 2
      irrigation solutions. RESULTS: No patients reported severe pain at any stage.
      Moderate pain was reported by 3% of patients (2/63 in each group) after 24 hours
      and by no patients beyond 24 hours, regardless of the irrigant used. Mild pain
      was more frequent but diminished rapidly (reported by 19% [12/63] of patients in
      the NaOCl group and 16% [10/63] in the CLX group at 24 hours, by 10% [6/63] in
      the NaOCl group and 11% [7/63] in the CLX group at 48 hours, by 3% [2/63] in both
      groups at 72 hours and by 2% [1/63] in both groups at 7 days). There were no
      statistically significant differences in postoperative pain between the 2 groups
      at any time point (p > 0.05). CONCLUSIONS: The incidence of postoperative pain
      after single-visit endodontic treatment of chronic apical periodontitis with pulp
      necrosis was uniformly low, regardless of the irrigant used.

PMID- 22985897
TI  - Physiology and pharmacology of nonbisphosphonate drugs implicated in
      osteonecrosis of the jaw.
AB  - Patients undergoing cancer chemotherapy are living longer and with better quality
      of life, and they require dental care both during and after their treatments.
      Bisphosphonates have been associated with drug-related osteonecrosis of the jaw
      (ONJ) since the discoveries of Marx in 2003 and Ruggiero and Woo in 2008. Recent
      literature has indicated a similar association with nonbisphosphonate drugs used
      in cancer therapy. Denosumab, an osteoclast inhibitor with applications in
      orthopedics and oncology, causes ONJ at a rate comparable to that for
      intravenously administered bisphosphonates. Case reports and drug agency records
      have indicated a correlation between ONJ and the neoangiogenesis inhibitors
      bevacizumab and sunitinib, which are used to treat many common cancers. The
      pharmacologic mechanisms of these 3 drugs appear distinct, yet a common effect on
      bone metabolism may occur in susceptible hosts. This review explores the
      mechanisms of these drugs that could lead to ONJ, according to current scientific
      understanding. The American Academy of Oral and Maxillofacial Surgeons has
      provided detailed recommendations for the management of bisphosphonate-related
      ONJ, which we suggest should also be applied in the management of patients with
      exposure to denosumab, bevacizumab and sunitinib.

PMID- 22985898
TI  - New dental trauma guidelines for permanent teeth: a perspective.

PMID- 22985899
TI  - Adherence to CONSORT harms-reporting recommendations in publications of recent
      analgesic clinical trials: an ACTTION systematic review.
AB  - Recommendations for harms (ie, adverse events) reporting in randomized clinical
      trial publications were presented in a 2004 extension of the Consolidated
      Standards of Reporting Trials (CONSORT) statement. Our objectives were to assess
      harms reporting in 3 major pain journals (European Journal of Pain, Journal of
      Pain, and PAIN(r)) to determine whether harms reporting improved following
      publication of the 2004 CONSORT recommendations, and to examine study factors
      associated with adequacy of harms reporting. A total of 101 randomized, double
      blind, noninvasive pharmacologic trials were identified in the 2000-2003 (epoch
      1) and 2008-2011 (epoch 2) issues of these journals. Out of 10 reporting
      recommendations, the mean number fulfilled was 6.08 (SD2.65). Although more harms
      recommendations were fulfilled in epoch 2 (m(2)=6.49, SD2.66) than in epoch 1
      (m(1)=5.39, SD2.52; P=0.04), only the recommendation to report harms per arm was
      satisfied by >90% of trials in epoch 2, whereas <60% reported withdrawals due to
      harms. Several trial characteristics (study design, participant type, pain type,
      frequency of treatment administration, treatment administration method, sponsor,
      and number of randomized participants) were significantly associated with harms
      reporting. However, when trial characteristics and epoch were entered into a
      multiple regression analysis, only trials studying pain patients, those using
      oral treatments, and industry-sponsored trials were associated with better harms
      reporting. Despite some improvement in harms reporting, greater improvement is
      needed to provide informative, consistent reporting of adverse events and safety
      in analgesic clinical trials.

PMID- 22985901
TI  - Thermal preferences of wintering snails Planorbarius corneus (L.) exposed to
      lipopolysaccharide and zymosan.
AB  - Fever is regarded as a physiological response to infection both in endothermic
      and ectothermic animals. In ectotherms, fevers are achieved only behaviorally,
      and has been described in many vertebrates' and few invertebrates' groups. In
      snails only symptoms of reverse fever as a response to trematode invasion were
      found. Present work reports on the effects of two different pyrogens -
      lipopolysaccharide extracted from Escherichia coli (LPS), and zymosan - from
      Saccharomyces cerevisiae on the thermal behavior of wintering (studied during a
      winter season) specimens of the Planorbarius corneus (L.). Using the thermal
      gradient protocol we demonstrate that the individuals of this snail species
      responded with behavioral fevers to dosages of pyrogens. LPS injection to the
      surface of the snail's foot at a dose of 10 MUg/g resulted in a significant
      increase in preferred temperature at 5h after injection. Similarly zymosan at a
      dose of 0.5 and 1.0 MUg/g - caused fever at 8h and 9h respectively. Average
      temperature chosen by feverish animals after latency period reached 28.7+/-0.41 
      degrees C (LPS), 28.1+/-0.43  degrees C (zymosan 1.0 MUg/g) or 25.5+/-0.33 
      degrees C (zymosan 0.5 MUg/g). We conclude, therefore, that snails are capable of
      reacting with fever to selected pathogen associated factors, and P. corneus can
      be used as a model to study a behavioral fever phenomenon in invertebrate
      animals.

PMID- 22985900
TI  - Brain networks predicting placebo analgesia in a clinical trial for chronic back
      pain.
AB  - A fundamental question for placebo research is whether such responses are a
      predisposition, quantifiable by brain characteristics. We examine this issue in
      chronic back pain (CBP) patients who participated in a double-blind brain imaging
      (functional magnetic resonance imaging) clinical trial. We recently reported that
      when the 30 CBP participants were treated, for 2 weeks, with topical analgesic or
      no drug patches, pain and brain activity decreased independently of treatment
      type and thus were attributed to placebo responses. Here we examine in the same
      group brain markers for predicting placebo responses--that is, for
      differentiating between posttreatment persistent CBP (CBPp) and decreasing CBP
      (CBPd) groups. At baseline, pain and brain activity for rating spontaneous
      fluctuations of back pain were not different between the 2 groups. However, on
      the basis of brain activity differences after treatment, we identified that at
      baseline the extent of information shared (functional connectivity) between left
      medial prefrontal cortex and bilateral insula accurately (0.8) predicted
      posttreatment groups. This was validated in an independent cohort. Additionally,
      by means of frequency domain contrasts, we observe that at baseline, left
      dorsolateral prefrontal cortex high-frequency oscillations also predicted
      treatment outcomes and identified an additional set of functional connections
      distinguishing treatment outcomes. Combining medial and lateral prefrontal
      functional connections, we observe a statistically higher accuracy (0.9) for
      predicting posttreatment groups. These findings indicate that placebo response
      can be identified a priori at least in CBP, and that neuronal population
      interactions between prefrontal cognitive and pain processing regions
      predetermine the probability of placebo response in the clinical setting.

PMID- 22985902
TI  - Histological survey of Pacific oysters Crassostrea gigas (Thunberg) in Galicia
      (NW Spain).
AB  - In Galicia, there is an increasingly interest among representatives of the oyster
      industry in the development of Pacific oyster Crassostrea gigas culture.
      Nevertheless severe mortalities and emerging health problems in this species have
      been recently reported in European farming areas. A histological survey was
      performed from 2004 to 2009 to assess health status in both cultured and wild
      Galician oysters. Different symbiotic organisms and conditions were detected,
      including viral gametocytic hypertrophy (VGH) which is reported here for first
      time in Spanish coast. VGH, prokaryote-like colonies and ciliates were observed
      in oyster tissues without causing host damage. A haplosporidian infection,
      copepods inducing lesions and a cellular proliferative disorder were detected in
      some samples causing moderate host damage; their low prevalence suggests these
      parasites are not a threat for C. gigas in Galicia. None of the parasites
      detected is OIE (Office International des Epizooties: the World Organization for
      Animal Health) notifiable. Although the current study did not identify any
      pathogens or diseases of concern, it provides important prevalence baseline data
      for future health and epidemiological assessments needed to better understanding
      the existing and emerging health problems in this species.

PMID- 22985903
TI  - Primary T-cell immunodeficiency with immunodysregulation caused by autosomal
      recessive LCK deficiency.
AB  - BACKGROUND: Signals emanating from the antigen T-cell receptor (TCR) are required
      for T-cell development and function. The T lymphocyte-specific protein tyrosine
      kinase (Lck) is a key component of the TCR signaling machinery. On the basis of
      its function, we considered LCK a candidate gene in patients with combined
      immunodeficiency. OBJECTIVE: We identify and describe a child with a T-cell
      immunodeficiency caused by a homozygous missense mutation of the LCK gene
      (c.1022T>C) resulting from uniparental disomy. METHODS: Genetic, molecular, and
      functional analyses were performed to characterize the Lck deficiency, and the
      associated clinical and immunologic phenotypes are reported. RESULTS: The mutant
      LCK protein (p.L341P) was weakly expressed with no kinase activity and failed to
      reconstitute TCR signaling in LCK-deficient T cells. The patient presented with
      recurrent respiratory tract infections together with predominant early-onset
      inflammatory and autoimmune manifestations. The patient displayed CD4(+) T-cell
      lymphopenia and low levels of CD4 and CD8 expression on the T-cell surface. The
      residual T lymphocytes had an oligoclonal T-cell repertoire and exhibited a
      profound TCR signaling defect, with only weak tyrosine phosphorylation signals
      and no Ca(2+) mobilization in response to TCR stimulation. CONCLUSION: We report
      a new form of T-cell immunodeficiency caused by a LCK gene defect, highlighting
      the essential role of Lck in human T-cell development and responses. Our results
      also point out that defects in the TCR signaling cascade often result in abnormal
      T-cell differentiation and functions, leading to an important risk factor for
      inflammation and autoimmunity.

PMID- 22985904
TI  - [Impact of sentinel node technique on the survival in patients with vulvar
      cancer: analysis of the Surveillance, Epidemiology, and End Results (SEER)
      database].
AB  - OBJECTIVES: Vulvar cancer is usually treated with vulvectomy and bilateral groin
      lymphadenectomy, which result in serious morbidities while only 30% of patients
      have positive nodes. The sentinel node technique has good sensitivity and
      specificity for detecting lymph node involvement while minimizing postoperative
      morbidity. The aim of this study was to evaluate the specific and overall
      survival impact of sentinel lymph node procedure versus inguinofemoral
      lymphadenectomy in patients with vulvar cancer. PATIENTS AND METHODS: This is a
      retrospective study from the Surveillance, Epidemiology, and End Results (SEER)
      database on patients with vulvar squamous cell carcinoma, T1 or T2 stage,
      metastatis-free, followed between 2004 and 2008. RESULTS: One thousand and thirty
      eight patients had a systematic groin lymphadenectomy and 56 a sentinel node
      technique (including 22 with an associated lymphadenectomy because of a positive
      sentinel node). There is no significant difference in overall or specific
      survival between the two groups. In multivariate analysis, age, T stage and nodal
      status are prognostic factors for overall and specific mortality (P<0.05).
      DISCUSSION AND CONCLUSION: Sentinel node technique is not associated with an
      excess risk of mortality or recurrence.

PMID- 22985905
TI  - Coexistence of two distinct intragenic dystrophin deletions in two maternal
      cousins with Duchenne Muscular Dystrophy.
AB  - The identification of two independent mutations is rarely described between
      affected members of the same family with Duchenne Muscular Dystrophy. This study
      reports the presence of two distinct intragenic dystrophin deletions in a Turkish
      family. Exon 54 deletion was identified originally in the proband, whereas his
      maternal cousin had deletions of exons 43-50 in the dystrophin gene. As
      indicated, only the mother of the proband was identified as exon 54 deletion
      carrier however, the proband's cousin was detected as a sporadic case. These
      molecular genetic data reveal an interesting and novel mixture, in the same
      family, of both mutations of the same gene.

PMID- 22985906
TI  - Effects of three weeks of mild sleep restriction implemented in the home
      environment on multiple metabolic and endocrine markers in healthy young men.
AB  - OBJECTIVES: Evidence for a causal relationship between sleep-loss and metabolism
      is derived primarily from short-term sleep deprivation studies in the laboratory.
      The objective of this study was to investigate whether small changes in sleep
      duration over a three week period while participants are living in their normal
      environment lead to changes in insulin sensitivity and other metabolic
      parameters. METHODS: Nineteen healthy, young, normal-weight men were randomised
      to either sleep restriction (habitual bedtime minus 1.5h) or a control condition
      (habitual bedtime) for three weeks. Weekly assessments of insulin sensitivity by
      hyperinsulinaemic-euglycaemic clamp, anthropometry, vascular function, leptin and
      adiponectin were made. Sleep was assessed continuously using actigraphy and
      diaries. RESULTS: Assessment of sleep by actigraphy confirmed that the
      intervention reduced daily sleep duration by 01:19 +/- 00:15 (SE; p<0.001). Sleep
      restriction led to changes in insulin sensitivity, body weight and plasma
      concentrations of leptin which varied during the three week period. There was no
      effect on plasma adiponectin or vascular function. CONCLUSIONS: Even minor
      reductions in sleep duration lead to changes in insulin sensitivity, body weight
      and other metabolic parameters which vary during the exposure period. Larger and
      longer longitudinal studies of sleep restriction and sleep extension are
      warranted.

PMID- 22985907
TI  - Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the
      neonatal mouse brain: possible role for IL-6 trans-signaling in brain development
      and functional neurobehavioral outcomes.
AB  - Adverse neurodevelopmental outcomes are linked to perinatal production of
      inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for
      maternal elevation in IL-6 has been established in determining neurobehavioral
      outcomes in the offspring and considered the primary target mediating the fetal
      inflammatory response, questions remain as to the specific actions of IL-6 on the
      developing brain. CD-1 male mice received a subdural injection of the bioactive
      fusion protein, hyper IL-6 (HIL-6) on postnatal-day (PND)4 and assessed from
      preweaning until adulthood. Immunohistochemical evaluation of astrocytes and
      microglia and mRNA levels for pro-inflammatory cytokines and host response genes
      indicated no evidence of an acute neuroinflammatory injury response. HIL-6
      accelerated motor development and increased reactivity to stimulation and number
      of entries in a light/dark chamber, decreased ability to learn to withhold a
      response in passive avoidance, and effected deficits in social novelty behavior.
      No changes were observed in motor activity, pre-pulse startle inhibition, or
      learning and memory in the Morris water maze or radial arm maze, as have been
      reported for models of more severe developmental neuroinflammation. In young
      animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP
      processes in the cortex was evident by immunohistochemistry. The non-hydroxy
      cerebroside fraction of cerebral lipids was increased. These results provide
      evidence for selective effects of IL-6 signaling, particularly trans-signaling,
      in the developing brain in the absence of a general neuroinflammatory response.
      These data contribute to our further understanding of the multiple aspects of IL
      6 signaling in the developing brain.

PMID- 22985908
TI  - Plasma myeloperoxidase levels correlate with hepatocellular carcinoma in chronic
      hepatitis C.
AB  - Myeloperoxidase (MPO) is an enzyme responsible for generating hypochlorous acid
      and reactive oxidants that may lead to liver injury and cancer in hepatitis C
      (HCV) infection. MPO expression level is regulated by a polymorphism in the
      promoter region -463 of MPO gene. In the current study, MPO plasma levels and the
      G-463A MPO polymorphism were determined in 158 chronically HCV infected patients
      with and without hepatocellular carcinoma (HCC). MPO plasma levels were
      determined using a commercially ELISA kit. The G-463A MPO polymorphism was
      accessed by real time PCR using TaqMan probes. The MPO plasma levels of patients
      with HCV-HCC were higher in comparison to patients with chronic hepatitis or with
      those patients with severe fibrosis (p=0.01 and p=0.04, respectively). The MPO G
      463A polymorphism was not associated with HCV outcome. These findings suggest MPO
      levels monitoring may be a potential biological marker to HCC screening in
      patients with HCV.

PMID- 22985909
TI  - Interplay between vitamin D and the drug metabolizing enzyme CYP3A4.
AB  - Cytochrome P450 3A4 (CYP3A4) is a multifunctional enzyme involved in both
      xenobiotic and endobiotic metabolism. This review focuses on two aspects:
      regulation of CYP3A4 expression by vitamin D and metabolism of vitamin D by
      CYP3A4. Enterohepatic circulation of vitamin D metabolites and their conjugates
      will be also discussed. The interplay between vitamin D and CYP3A4 provides new
      insights into our understanding of how enzyme induction can contribute to vitamin
      D deficiency. This article is part of a Special Issue entitled 'Vitamin D
      Workshop'.

PMID- 22985910
TI  - Predictors of radiotherapy induced bone injury (RIBI) after stereotactic lung
      radiotherapy.
AB  - BACKGROUND: The purpose of this study was to identify clinical and dosimetric
      factors associated with radiotherapy induced bone injury (RIBI) following
      stereotactic lung radiotherapy. METHODS: Inoperable patients with early stage non
      small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3
      fractions, and had a minimum of 6 months follow up were reviewed. Archived
      treatment plans were retrieved, ribs delineated individually and treatment plans
      re-computed using heterogeneity correction. Clinical and dosimetric factors were
      evaluated for their association with rib fracture using logistic regression
      analysis; a dose-event curve and nomogram were created. RESULTS: 46 consecutive
      patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months
      (m) (range 6 - 51 m) were eligible. 41 fractured ribs were detected in 17
      patients; median time to fracture was 21 m (range 7 - 40 m). The mean maximum
      point dose in non-fractured ribs (n=1054) was 10.5 Gy +/- 10.2 Gy, this was
      higher in fractured ribs (n=41) 48.5 Gy +/- 24.3 Gy (p<0.0001). On univariate
      analysis, age, dose to 0.5 cc of the ribs (D0.5), and the volume of the rib
      receiving at least 25 Gy (V25), were significantly associated with RIBI. As D0.5
      and V25 were cross-correlated (Spearman correlation coefficient: 0.57, p<0.001),
      we selected D0.5 as a representative dose parameter. On multivariate analysis,
      age (odds ratio: 1.121, 95% CI: 1.04 - 1.21, p=0.003), female gender (odds ratio:
      4.43, 95% CI: 1.68 - 11.68, p=0.003), and rib D0.5 (odds ratio: 1.0009, 95% CI:
      1.0007 - 1.001, p<0.0001) were significantly associated with rib fracture.Using
      D0.5, a dose-event curve was constructed estimating risk of fracture from dose at
      the median follow up of 25 months after treatment. In our cohort, a 50% risk of
      rib fracture was associated with a D0.5 of 60 Gy. CONCLUSIONS: Dosimetric and
      clinical factors contribute to risk of RIBI and both should be included when
      modeling risk of toxicity. A nomogram is presented using D0.5, age, and female
      gender to estimate risk of RIBI following SBRT. This requires validation.

PMID- 22985911
TI  - The synergistic effect of EGFR tyrosine kinase inhibitor gefitinib in combination
      with aromatase inhibitor anastrozole in non-small cell lung cancer cell lines.
AB  - BACKGROUND: Several studies implicated that lung cancer progression was governed
      by the interaction between estrogen receptor (ER) and epidermal growth factor
      receptor (EGFR) signaling pathways. Combined targeting of EGFR and ER may have
      the synergistic effect in lung cancer treatment. The aim of this study was to
      explore the potential utility of inhibiting these two pathways with combination
      of anastrozole and gefitinib in non-small cell lung cancer (NSCLC) cell lines.
      MATERIALS AND METHODS: The expression levels of ER (ER-alpha and ER-beta) in lung
      cancer cell lines (A549, H460, SPC-A-1, H1299) and normal bronchus epithelial
      cell BEAS-2B were detected using real-time PCR and Western blot.
      Immunocytochemistry was used to locate ER-alpha and ER-beta in cell line with
      highest ER expression levels. The cells were treated with anastrozole or
      gefitinib alone or in combination. The cell proliferation inhibition was detected
      by the CCK8 assay, cell cycle and apoptosis effects were detected by flow
      cytometry; the expression levels of phosphorylated-EGFR (p-EGFR), ERK,
      phosphorylated-ERK (p-ERK), AKT and phosphorylated-AKT (p-AKT) were detected by
      Western blot. RESULTS: Among these cell lines the expression levels of ER in A549
      cells were highest. In A549 cell line, ER-alpha was mainly localized in the
      cytoplasm, whereas ER-beta was mainly localized in the cytoplasm and to a lesser
      degree in the nucleus. The combination of two drugs increased the proliferation
      inhibition rates for 24h, 48 h, 72 h to 37.66 +/- 1.02%, 63.41 +/- 2.02%, 70.50
      +/- 0.86%, respectively, which was closely associated with elevation of the G0/G1
      phase fraction (P<0.05). Apoptosis rates of A549 cells treated with anastrozole,
      gefitinib alone or in combination were 10.72 +/- 1.12%, 17.40+/-1.28%, 23.02 +/-
      2.32%, respectively (P<0.05). The synergistic effects of the combination therapy
      were accompanied by reduction of p-EGFR, p-ERK and p-AKT expression compared with
      individual treatment. CONCLUSIONS: The results of this study suggest that the
      combination of anastrozole and gefitinib compared with either drug alone can
      maximally inhibit cell proliferation, induce apoptosis, and affect downstream
      signaling pathways. Our study supports functional interaction between the ER and
      the EGFR pathways in lung cancer and provides a clinically exploitable strategy
      for non-small cell lung cancer patients.

PMID- 22985912
TI  - Effects of the radiocontrast agent iodixanol on endothelial cell morphology and
      function.
AB  - Iodinated radiocontrast media (RCM) are usually well tolerated, but their large
      and increasing use renders their toxicity a relevant problem, especially in high
      risk patients. The aim of the study was to investigate the possible toxic or
      activating effects of iodixanol on endothelial cells (EC) and the putative in
      vitro protective action of N-acetylcysteine and rosuvastatin. Morphology,
      oxidative status, redistribution of heat-shock protein 60 and secretion of
      proinflammatory products were studied in cultured human EC through confocal
      microscopy, immunofluorescence and immuno-enzymatic methods. EC reacted to
      iodixanol with shrinking and bulging, increase in intracellular oxidation and
      translocation of Heat Shock Protein 60 to the cell membrane. The secretion of
      proinflammatory products was strongly stimulated by sequential incubation of EC
      with iodixanol and TNFalpha (p<0.00001 for all tested molecules, namely TNFalpha,
      IL-8, sVCAM-1, MCP-1, and IL-6). N-acetylcysteine prevented morphologic and
      oxidative derangements, and significantly reduced proinflammatory product
      secretion (P range<0.0001 to<0.00001 for TNFalpha, VCAM-1, MCP-1, and IL-6);
      rosuvastatin inhibited morphology and oxidative modifications only. Our data help
      clarifying the mechanisms of early and late toxicity of RCM and support the use
      of anti-oxidant and anti-inflammatory agents for optimization of radiological
      procedures in high risk patients.

PMID- 22985913
TI  - Underassessment of weight and weight management in patients with diabetes: one
      more reason in support of weight management advice.
AB  - AIMS: The purpose of this study was to determine whether underassessment of
      weight affects weight management behaviors of overweight and obese individuals
      with diabetes and to determine whether weight management advice from health care
      professionals modifies the effect of underassessment of weight. METHODS: Data
      (n=979) from the 2006 and 2008 National Health and Nutrition Examination Survey
      were analyzed. Multivariate logistic regression was used to identify factors
      associated with underassessment of weight, weight management behaviors, and
      receipt of weight management advice from health care professionals. RESULTS:
      Underassessment of weight was common (26%). Men, overweight persons, Blacks and
      Hispanics were more likely to underassess their weight. Those who underassessed
      their weight were 53% less likely to report weight management behaviors, odds
      ratio 0.47 (95% CI=0.31-0.73). Weight management advice increased weight
      management behaviors among individuals who underassessed their weight, 3.49 (95%
      CI=1.70-7.18). CONCLUSIONS: Underassessment of weight can negatively affect
      weight management behaviors of overweight and obese individuals with diabetes.
      Weight management advice from health care professionals is important, and can
      modify the effect of underassessment of weight on weight management behaviors in
      this high risk group.

PMID- 22985914
TI  - [Causes of deaths in Portugal and challenges in prevention].
AB  - In Portugal, the hope of living, in terms of probability, either at birth or at
      65 years old, has reached levels that represent huge gains and certainly reflect
      the successful initiatives developed in many sectors in the last 30 years. In
      2008-2010, the average life expectancy at birth was 79.20 years for men and
      women. By contrast, in 1980, the average life expectancy at birth was 71.78
      years. Furthermore, premature mortality, defined as occurring before 70 years of
      age, expressed as rate, represents the likelihood of dying before this age, which
      is presently of 24.3%, meaning that one in four dies Portuguese citizen before
      reaching the age of 70. Main cause of deaths and the number of years in the
      Portuguese population that theoretically stops living when you die before the age
      of 70 (potential years lost), for both sexes, includes the following: traffic
      accidents with motor vehicles - 22,550 years; malignant tumor of trachea,
      bronchus and lung - 19,768 years, vascular brain diseases - 16,070 years, self
      injury caused intentionally - 14,753 years. It's important to analyze these
      figures and its evolution in order to allow an understanding of their impact and
      implement effective corrective measures. The contribution of actions and programs
      to prevent some of the above causes of deaths and potential years lost is still
      to be objectively interpreted but it is well known the importance of reducing
      risks factors as tobacco and alcohol consumption, encouraging balanced nutrition
      in calories and composition, promoting regular physical exercise and improving
      information and health education on the reduction of many chronic non
      communicable diseases, what in turn, reflects in the decline of premature
      mortality. It is essential to analyze the causes that anticipate the death of the
      Portuguese population and the cause of these causes, that is, their risk factors
      and design programs that reduce the exposure of citizens to avoidable risks,
      which is the essence of all public health programmes.

PMID- 22985915
TI  - [The importance of simulation in team training on obstetric emergencies: results
      of the first phase of the national plan for continuous medical training].
AB  - Obstetric emergencies are unexpected and random. The traditional model for
      medical training of these acute events has included lectures combined with
      sporadic clinical experiences, but this educational method has inherent
      limitations. Given the variety of manual skills that must be learned and high
      risk environment, Obstetrics is uniquely suited for simulation. New technological
      educational tools provide an opportunity to learn and master technical skills
      needed in emergent situations as well as the opportunity to rehearse and learn
      from mistakes without risks to patients. The goals of this study are to assess
      which are the factors that trainees associate to human fallibility before and
      after clinical simulation based training; to compare the confidence level to
      solve emergent obstetric situations between interns and experts with up to 5
      years of experience before and after training, and to determine the value that
      trainees give to simulation as a teaching tool on emergent events. 31 physicians
      participated at this course sessions. After the course, we verified changes in
      the factores that trainees associate to human fallibility, an increase in
      confidence level to solve emergent obstetric and an increase in the value that
      trainees give to simulation as a teaching tool.

PMID- 22985916
TI  - [Hypovitaminosis D in patients admitted to an internal medicine ward].
AB  - INTRODUCTION: Hypovitaminosis D (hypoD) is a vitamin deficiency that has been
      rising in the developed countries, due not only to inappropriate eating habits,
      but also because of lower sun exposure and lack of exercise. OBJECTIVE: To
      determine the prevalence of vitamin D deficiency and to analyze associated
      factors, in patients admitted to an Internal medicine Ward. METHODS: Cross
      sectional study which included 123 hospitalized patients admitted to an Internal
      Medicine Ward between April and May. Serum levels of vitamin D [25-hydroxyvitamin
      D, 25(OH)D] were determined and the sample divided into three groups based on
      25(OH)D levels: severe hypoD (<10ng/mL), moderate deficiency of 25(OH)D (>10ng/mL
      and <20ng/mL) and third group with normal levels of 25(OH)D (>20ng/mL).
      Demographic variables were recorded as were factors potentially related to
      vitamin D deficiency. RESULTS: In this sample (52.0% women) the average age was
      71 +/- 17 years, 67.5% of patients had severe hypoD, 25.2% moderate deficiency
      and 7.3% normal levels of vitamin D. The patients in the group with severe hypoD
      were older (p=0.027). In the same group there was a higher percentage of patients
      in the bedridden state (p=0.022), with higher impaired functional capacity
      (p=0.009) and with chronic renal insufficiency (p=0.011). In multivariate
      logistic regression analysis, factors associated with an increased likelihood of
      severe hypoD were: furosemide treatment [OR=3.673 (1.232-10.956) p=0.020] and
      albumin <=3.25 [OR=5.617 (2.257-13.981) p<0.001]. CONCLUSION: The high prevalence
      of hypoD (67.5%) in this sample expresses the need for systematic evaluation of
      serum levels of 25(OH)D, in order to initiate early treatment in patients with
      inadequate levels. Furosemide treatment and hypoalbuminaemia present an increased
      likelihood of being associated with severe hypoD. Treatment of this
      hypovitaminosis is warranted not only because of the clinical consequences
      related to bone loss, but also because of its relationship with hypoalbuminemia
      which is associated with a poorer prognosis in hospitalized patients.

PMID- 22985917
TI  - [Psychosocial characterization of a Portuguese lower limb amputee population].
AB  - OBJECTIVE: This study aims to describe psychosocial status in lower limb amputees
      referred to a Physical and Rehabilitation Medicine (PRM) department of a central
      Portuguese Hospital. METHODS: Cross-sectional study of 45 consecutive patients
      with lower limb amputation, referred to PMR consultation after hospital
      discharge. Of the initial sample, two patients were excluded from the analysis,
      and four patients refused to participate in the study. The socio-demographic,
      medical and surgical history were obtained through structured questionnaire, and
      clinical information regarding the characteristics of the amputation was
      abstracted from medical records. Functional capacity was assessed with the
      Amputee Mobility Predictor (AMP), quality of life through short-form 36 (SF36),
      and depressive and anxious symptoms by the Hospital Anxiety and Depression Scale
      (HADS). RESULTS: Out of 39 patients analyzed, 32 (82.1%) were men, aged [average
      (standard deviation): 67, 6 (12.57)] years, 28 (71.8%) were married, 30 (76.9%)
      were retired, 3 (7.7%) were unemployed, 4 (10.3%) were on sick leave, and 2
      (5.1%) were active. Regarding the cause of amputation, 36 (92.3%) were of
      vascular etiology, 1 (2.6%) caused by an infection, and 2 (5.1%) due to bone
      tumours, 23 (59%) had a transfemoral amputation, 10 (25.6%) had a transtibial
      amputation, and 6 (15.4%) had foot amputations of the foot. In the sample
      studied, 14 (35.9%) had pathological levels of anxiety (HADS-anxiety >= 8) and 15
      (38.5%) had clinical depression (HADS-depression >= 8). The evaluation of quality
      of life and general perception of health status, showed lower than average score
      especially in the physical dimensions with a physical component summary score of
      the SF36 [P50 (P25-P75): 31.4 (26.8-39.4)], and in the mental component summary
      of SF36 [P50 (P25-P75): 41.9 (31.8-48.3)]. In this sample, the data showed the
      AMP score [P50 (P25-P75): 8 (4-16)], ranging from 0 to 27. CONCLUSION: This
      sample has a high prevalence of depressive/anxious symptoms. Considering that
      these mood changes have a major impact on the adherence to the rehabilitation
      program, functional outcome and quality of life, its early identification and
      treatment should be part of their overall management.

PMID- 22985918
TI  - Prevalence of metabolic syndrome and diabetes on a high-risk population with
      suspected coronary artery disease.
AB  - OBJECTIVES: Metabolic syndrome and diabetes prevalence varies according to chosen
      definition, as well as with the geographical and ethnical group. No studies are
      available in Portuguese patients with suspected coronary artery disease. We
      analysed metabolic syndrome and diabetes prevalence in this specific population
      and compared definitions. METHODS: The study included 300 patients, with a mean
      age of 64 +/- 9 years, 59% males, admitted for an elective coronary angiography
      and we excluded patients with previous cardiac disease. Metabolic syndrome and
      diabetes prevalence was obtained. RESULTS: The adjusted prevalence of metabolic
      syndrome was found to be 39.3% (NCEP-ATP III criteria), 53.8% (IDF criteria) and
      48.4% (AHA/NHLBI). Adjusted prevalence of diabetes was 14.8% by the previous ADA
      definition and 36.4% with the new definition. Global agreement between metabolic
      syndrome definitions was 45.3%, with the highest value between AHA/NHLBI and NCEP
      ATP III (Kappa 0.821). Metabolic syndrome prevalence was highly age-dependent in
      both genders and more prevalent in females. Diabetes prevalence was also age
      dependent, with similar prevalence in both genders. The most frequent metabolic
      syndrome component was hypertension, followed by abdominal obesity, raised
      glucose, low HDL-cholesterol and finally increased triglycerides. It is also
      important to mention that 60% of the patients were under lipid-lowering treatment
      (56.6% with statins, 1.7% with fibrates and 1.7% with both). The most significant
      difference between genders for metabolic syndrome components is the high
      prevalence of abdominal obesity in females. CONCLUSIONS: In this high-risk
      population, metabolic syndrome prevalence is high, with similar diabetes
      prevalence compared with general population epidemiological studies.

PMID- 22985919
TI  - [Pediatric obesity: the reality of one consultation].
AB  - BACKGROUND: The prevalence of paediatric obesity is constantly rising. The
      association to cardiovascular risk, diabetes and psychosocial disturbances is a
      concern. Precocious identification and intervention is essential to reduce the
      negative impact on adult life. MATERIAL AND METHODS: Evaluation of the expression
      of comorbidities and the multidisciplinary intervention on nutritional status and
      body composition in obese children and adolescents, at six months follow-up on
      the Paediatric Obesity consultation. Retrospective analysis from the clinical
      files of under 17 years-old patients, followed from January 2005 to December
      2008. RESULTS: We followed 67 children and adolescents, mostly female. Overweight
      emerged at 4.6 years and the first evaluation in our consult occurred at 9.1
      years-old, on average. Primary health care colleagues referred most patients
      (47.8%). The commonest predictor of obesity was parental obesity (60%). Planned
      physical activity was poorer in the lowest school years. Severe obesity was the
      most prevalent type of obesity (70%). Both genders showed a different fat
      distribution (female: non-central; male: central). Frequent findings on physical
      examination were: striae, adipomastia, acanthosis nigricans and orthopedic
      changes. In the first evaluation, although 6% of patients have shown high blood
      pressure, 34.4% insulin resistance and 56.7% dyslipidemia, only 7.7% met criteria
      for metabolic syndrome. Other associated comorbidities were psychosocial problems
      (23.9%), asthma (16.4%), orthopedic (10.5%) and gastrointestinal (3%) diseases.
      BMI percentile reduction occurred in 51% of cases, after 6 months of
      intervention. The increase on physical activity was reported by 56.7% of
      patients. Bioelectrical impedance showed an average fat mass reduction of 0.8%.
      At the end of the studied period, dropout rate from this consultation was
      admirably high (28.4%). CONCLUSION: Multidisciplinary involvement of all health
      professionals, schools and family is essential for paediatric obesity
      intervention. Anthropometric evaluation should always include the waist
      circumference and BMI estimate. Bioelectrical impedance can be used to evaluate
      the individual changes in body composition. Changing lifestyle habits is still
      the most effective treatment as success will mainly depend on the patient and
      family motivation.

PMID- 22985921
TI  - Anatomic factors related to bisphosphonate osteonecrosis of the jaws: a
      Portuguese retrospective study.
AB  - AIMS: The objectives of this study of bisphosphonate-related osteonecrosis of the
      jaws (BRONJ) were to determine local distribution, possible anatomically
      associated or determinant factors and other bone involvement of the disease,
      contributing with this new data towards the establishment of its prevalence in
      Portugal. MATERIAL AND METHODS: The authors made a retrospective study of
      patients presenting BRONJ, at the Department of Stomatology of Santa Maria
      University Hospital, in Lisbon (42 cases) from 1st January 2004, to April 30rd,
      2011. SPSS Statistics was implemented. RESULTS: There was a higher prevalence of
      lesions in the lower jaw (66.7%), compared to the upper jaw (26.19%) and a
      significantly higher occurrence in alveolar bone (95.24%). The molars and
      premolars were the most affected areas (highest value at 6th sextant = 35.29%).
      In all cases, the onset of injury occurred after a medication period of up to 90
      days, spontaneously in 14.29% of patients. CONCLUSIONS: For severity, BRONJ was a
      significant anatomoclinical entity in all 42 new cases in this study, and for
      discomfort (pain) in 81.1% of them. There was an anatomic correlation between the
      occurrence of the disease and its location in the jaws. There was a clinical
      association with trauma and type, route and length of administration of the
      bisphosphonate, with Zoledronate being administered intravenously in 76.19% of
      the cases. The jaws were the unique place where the disease occurred. Preventive
      measures should be implemented, avoiding trauma, and performing surgical
      procedures within 90 days after prescription.

PMID- 22985920
TI  - P-cadherin as prognostic factor for loco-regional relapse in breast cancer.
AB  - BACKGROUND: Breast cancer is the most frequent malignant tumor and the leading
      cause of cancer death in women in Portugal. Due to its relation to an increase in
      distant metastasis and subsequent death, loco-regional relapse is one major
      concern in breast cancer women. Several classic prognostic factors as tumour
      size, nodal stage, histological grade, HER2 status and hormonal receptors have
      been identified as the most important factors for determining loco-regional
      relapse, disease free and overall survival. However, there is heterogeneity in
      prognosis and tumor behaviour in patients with identical disease staging and a
      similar pattern of expression of known molecular markers, hence the need to
      discover new prognostic factors. One of the possibilities is P-cadherin, already
      described by researchers as a possible independent marker of prognosis in breast
      cancer. The aim of this work was to study in a retrospective series of patients
      the correlation of P-cadherin expression with loco-regional recurrence in breast
      cancer women. MATERIAL AND METHODS: We analyzed the clinical records of 1432
      consecutive patients with breast cancer and treated in a University Hospital over
      a 10 year period. Patients with loco-regional relapse (n=101) without prior or
      simultaneous distant disease were selected as case group. Control group consisted
      of patients with more than 10 years follow-up and without disease progression.
      For both groups demographic, clinical, pathological and molecular markers were
      analyzed. Tissue micro-arrays were constructed to study P-cadherin expression
      from 86 tumors with available paraffin embedded blocks. RESULTS: Mean time to
      recurrence was 41 months and mean survival time after recurrence was 33 months,
      with a 5-year survival rate of 55%. Tumour size, nodal status and histological
      grade were identified as independent markers of prognosis. P-cadherin was
      associated with higher histological grades and hormone negative tumours. P
      cadherin was identified as an independent prognostic marker for disease free
      survival, but not for overall survival. CONCLUSION: P-cadherin was related to
      other known factors of worse prognosis and had an independent relation to disease
      free survival. P-cadherin might constitute a novel therapeutic target, but its
      real biological value is yet to be determined. Doubt persists whether it is an
      independent marker of tumour behaviour or only a surrogate marker of a set of
      clinical and molecular features related with worse prognosis.

PMID- 22985922
TI  - [Mephedrone, the new designer drug of abuse: pharmacokinetics, pharmacodynamics
      and clinical and forensic issues].
AB  - Mephedrone is a semisynthetic derivative of cathinone used as a drug of abuse.
      Similar to amphetamine, both in chemical structure and associated signs and
      symptoms, has gained popularity since 2007 and it is currently the sixth most
      abused drug in United Kingdom. It can be easily purchased by the internet or
      smart shops where it is advertised as a fertilizer for plants or bath salts,
      although such efficacy was never proved. This article aims to review the state-of
      the-art literature of mephedrone, particularly its chemical structure, forms of
      presentation, pharmacokinetics, pharmacodynamics, acute intoxications, diagnosis
      and therapy of intoxications. Mephedrone is mainly sought for the following
      symptoms: euphoria, social disinhibition, empathy, and increased libido. However,
      its use is associated with several adverse effects on cardiovascular,
      gastrointestinal, neurological, psychiatric and genitourinary systems, among
      others. There are also reported cases of consumers who have developed tolerance
      and dependence after a regular abuse of mephedrone. Several deaths in the United
      Kingdom have been confirmed as being directly related to the consumption of
      mephedrone. Currently this drug is legally controlled in many countries, but
      little is known about its pharmacokinetics and pharmacodynamics. Most data comes
      only from users and health professional's reports and internet surveys. Recently,
      the Portuguese Law 13/2012, 26 of March, included mephedrone in the list of
      controlled substances, and therefore it is important to better understand this
      xenobiotic.

PMID- 22985923
TI  - Thioridazine: an old neuroleptic effective against totally drug resistant
      tuberculosis.
AB  - Globally, tuberculosis infections continue to increase their resistance to
      antibiotics. Multidrug resistant tuberculosis infections (MDR TB) have progressed
      to extensively drug resistance status (XDR TB) and the latter have evolved in
      some parts of the world to totally drug resistant (TDR TB) infections. MDR TB is
      difficult to treat successfully, and when therapy is ineffective, a single case
      can cost almost $500,000. When the infection is XDR TB therapy is mostly
      unsuccessful and is accompanied with high mortality. TDR TB-a yet to be defined
      infection, is resistant to all forms of therapy and mortality is almost certain.
      We have, over a period of 14 years, studied thioridazine (TZ) an old neuroleptic
      that we have shown to: i) have in vitro activity against all antibiotic resistant
      forms of Mycobacterium tuberculosis; ii) have activity against intracellular
      Mycobacterium tuberculosis regardless of its antibiotic resistance status; iii)
      cure the infected mouse of an antibiotic susceptible and MDR TB infections; and,
      iv) when used in combination with antibiotics used for therapy of tuberculosis,
      would render the organism significantly more susceptible. These studies have
      guided our Argentinian colleagues to treat successfully XDR TB infections with
      thioridazine in combination with three antibiotics to which the infection was
      initially resistant. This mini review will describe our further work and the
      mechanisms by which TZ alone and in combination with antibiotics cures an XDR TB
      infection and why it is expected to cure TDR TB infections as well. The concepts
      presented are totally new and because they focus on the activation of killing by
      non-killing macrophages where Mycobacterium tuberculosis normally resides during
      infection, and coupled to the inhibition of efflux pumps which contribute to the
      antibiotic resistant status, effective therapy of any antibiotic resistant TB
      infection is possible. Because TZ is cheap and therefore affordable to any
      economically disadvantaged country, and will produce no harm when appropriate
      measures are taken, it is the ideal drug for immediate use in countries that have
      high frequencies of MDR, XDR and TDR TB infections.

PMID- 22985924
TI  - [Hypokalemic paralysis: the first presentation of primary Sjogren's syndrome].
AB  - The Sjogren's syndrome is a systemic autoimmune disorder characterized by chronic
      inflammation of the exocrine glands with extraglandular manifestations in up to
      25% patients. Renal involvement occurs in 18.4-67% of cases, with
      tubulointerstitial nephritis being the most frequent pathology. We present the
      case of a 37 year-old woman admitted because of generalized grade 2 muscle
      weakness which developed over a week. We detected: hypokalemia, rhabdomyolysis,
      urinary pH 6.5, proteinuria and metabolic acidemia. The laboratory tests
      suggestive of distal renal tubular acidosis with hypokalaemia led to the
      diagnosis of lymphoplasmocytic tubulointerstitial nephritis, which was confirmed
      by renal biopsy, and to a clinical suspicion of Sjogren's syndrome. Primary
      Sjogren's syndrome was diagnosed in this patient based on the following criteria:
      xerophthalmia, xerostomia, sialadenitis, positive anti-SSA and anti-SSB
      antibodies, and absence of criteria for lupus and rheumatoid arthritis. During
      hospitalization, the patient developed deep vein thrombosis. Tests showed
      positive antiphospholipid antibodies and the diagnosis of secondary
      antiphospholipid syndrome was made. She was treated with potassium, bicarbonate,
      steroids, ramipril and warfarin. The authors wish to highlight the extraglandular
      manifestations and in particular the rarity of hypokalemic paralysis as the
      presenting manifestation of primary Sjogren's syndrome.

PMID- 22985925
TI  - [Guidelines for high-quality use of biologic therapies in adults with plaque
      psoriasis].
AB  - Psoriasis is an inflammatory dermatosis, affecting approximately 2% of the
      population, with predominantly skin and joint involvement but also associated
      with considerable comorbidities. Approximately 20% to 30% of patients have
      moderate to severe disease uncontrollable with topical therapy. Traditional
      systemic therapy - oral PUVA, retinoids, cyclosporin and methotrexate - may
      induce organ specific toxicity and a significant number of patients are
      unresponsive, intolerant or have specific contraindications to its use. With the
      increased understanding of the pathogenesis of psoriasis, multiple biologic
      agents have been introduced. In the last years there has been an increased
      utilization of these agents and several studies were designed to evaluate their
      efficacy and safety. Currently, four biologics have been already approved by EMEA
      (European Medicines Agency) for the treatment of plaque psoriasis, 3 anti
      TNFalpha (adalimumab, etanercept and infliximab) and one anti-IL12/23p40
      (ustecinumab). In the present article we update the prior published guidelines
      (Trabalhos da SPDV 2010;68(1):47-68 and 2011;69(4):531-553) due to the recent
      progress in the knowledge and therapeutic options in these area. These
      recommendations should be used with caution and treatment should be tailored to
      meet individual patient's needs and each specific clinical situation.

PMID- 22985926
TI  - [Symptomatic splenic sarcoidosis].

PMID- 22985927
TI  - Polyphenols from Pistacia lentiscus and Phillyrea latifolia impair the
      exsheathment of gastro-intestinal nematode larvae.
AB  - The infection of grazing ruminants with gastro-intestinal nematodes (GINs) is a
      severe problem in the Middle East. However, goats that graze the south-western
      slopes of the Carmel Heights in Israel have very low faecal egg counts, despite
      high grazing density. We hypothesized that polyphenols from Pistacia lentiscus L.
      and/or Phillyrea latifolia L. - both prevalent woody species of the region that
      are consumed by goats - have anthelmintic bioactivity. We tested this hypothesis
      by using the larval exsheathment inhibition assay (LEIA). Extracts were prepared
      from leaves of either plant species using 70% ethanol (E70), 100% ethanol (E100),
      or boiling water (W). Larvae were incubated in a phosphate-buffered saline
      solution with or without plant extract (1200MUg/ml) and then exposed to an
      exsheathment solution expected to elicit 100% exsheathment after one hour. All
      extraction methods of P. lentiscus were highly effective at inhibiting larval
      exsheathment, but higher potency was found for the E70 than for E100 extraction
      method, while W was intermediate. Only the E70 extract of P. latifolia was highly
      effective relative to the control. The E70 extract of P. lentiscus had more than
      7 times the potency of the E70 extract of P. latifolia. Irrespective of solvent
      and tannin-equivalent used, P. lentiscus contained more than double the quantity
      of total polyphenols than P. latifolia. The polyphenols of P. lentiscus consisted
      mainly of galloyl derivatives (63.6%), flavonol glucosides (28.6%), and catechin
      (7.8%). In P. latifolia, oleuropein and its derivative tyrosol accounted for 49.3
      and 23.1% of phenolics, respectively, the remainder being flavones (luteolin and
      quercetin) and their glucoside derivatives. Results of the LEIA test suggest that
      extracts of tannin-rich plants interfere with the very early stage of host
      invasion and that high concentration of galloylated derivatives may explain
      anthelmintic activity.

PMID- 22985928
TI  - Evaluation of in vitro and in vivo inhibitory effects of fusidic acid on Babesia
      and Theileria parasites.
AB  - Fusidic acid known to has antibacterial, antifungal, and antimalarial activities.
      Fusidic acid blocks translation elongation factor G gene in Plasmodium
      falciparum. In the present study, the inhibitory effects of fusidic acid on the
      in vitro growth of bovine and equine Babesia parasites were evaluated. The
      inhibitory effect of fusidic acid on the in vivo growth of Babesia microti was
      also assessed. The in vitro growth of four Babesia species that were tested was
      significantly inhibited (P<0.05) by micromolar concentrations of fusidic acid
      (IC(50) values=144.8, 17.3, 33.3, and 56.25 MUM for Babesia bovis, Babesia
      bigemina, Babesia caballi, and Theileria equi, respectively). Combinations of
      fusidic acid with diminazene aceturate synergistically potentiated its inhibitory
      effects in vitro on B. bovis and B. caballi. In B. microti-infected mice, fusidic
      acid caused significant (P<0.05) inhibition of the growth of B. microti at the
      dose of 500 mg/kg BW relative to control group. These results indicate that
      fusidic acid might be incorporated in treatment of babesiosis.

PMID- 22985929
TI  - Effect of supplemental sericea lespedeza leaf meal pellets on gastrointestinal
      nematode infection in grazing goats.
AB  - Feeding sun-dried sericea lespedeza [SL; Lespedeza cuneata (Dum-Cours.) G. Don.]
      reduces gastrointestinal nematode (GIN) infection in goats fed in confinement,
      but effects of this forage when fed as a supplement to goats on pasture are
      unclear. A study was completed in which supplemental feeds (75 and 95% SL leaf
      meal pellets and a commercial pellet, all fed at 0.91 kg/head/day) were offered
      to thirty growing male Spanish goats (9 months old, 20.6 +/- 2.8 kg,
      10/treatment) grazing perennial warm-season grass pastures in Fort Valley, GA,
      from September to November, 2010. Fecal and blood samples were taken from
      individual animals weekly to determine fecal egg count (FEC) and packed cell
      volume (PCV), respectively, and animal weights were recorded at the start and end
      of the trial. After 11 weeks grazing, animals were slaughtered for recovery,
      counting, and speciation of adult GIN from the abomasum and small intestines.
      There was no difference in FEC between goats fed the 75 and 95% SL leaf meal
      pellets, but both groups had lower (P<0.05) FEC than the goats fed the commercial
      pellets from days 35 to 77. The PCV values were not affected by the dietary
      treatments. Animal gain per day averaged 102.0, 77.2, and 53.3g for goats fed 95%
      SL, commercial, and 75% SL pellets, respectively (P<0.05). The 95% SL leaf meal
      pellet goats had 93.0 and 47.3% fewer (P<0.05) total (male+female) adult
      Haemonchus contortus and Teladorsagia circumcincta, respectively, than control
      animals, while only male H. contortus were lower (47.6%; P<0.05) in 75% SL-fed
      goats compared with commercial pellet-fed animals. Feeding supplemental SL leaf
      meal pellets improved animal performance (95% SL pellets) and reduced worm
      burdens (75 and 95% SL pellets) in young grazing goats and is a useful tool for
      natural GIN control in small ruminants.

PMID- 22985930
TI  - Anti-apoptotic function of the E2F transcription factor 4 (E2F4)/p130, a member
      of retinoblastoma gene family in cardiac myocytes.
AB  - The E2F4-p130 transcriptional repressor complex is a cell-cycle inhibitor in
      mitotic cells. However, the role of E2F4/p130 in differentiated cells is largely
      unknown. We investigated the role of E2F4/p130 in the regulation of apoptosis in
      postmitotic cardiomyocytes. Here we demonstrate that E2F4 can inhibit hypoxia
      induced cell death in isolated ventricular cardiomyocytes. As analyzed by
      chromatin immunoprecipitation, the E2F4-p130-repressor directly blocks
      transcription of essential apoptosis-related genes, E2F1, Apaf-1, and p73alpha
      through recruitment of histone deacetylase 1 (HDAC1). In contrast, diminution of
      the E2F4-p130-HDAC1-repressor and recruitment of E2F1 and histone acetylase
      activity to these E2F-regulated promoters is required for the execution of cell
      death. Expression of kinase-dead HDAC1.H141A or HDAC-binding deficient
      p130DeltaHDAC1 abolishes the antiapoptotic effect of E2F4. Moreover, histological
      examination of E2F4(-/-) hearts revealed a markedly enhanced degree of
      cardiomyocyte apoptosis. Taken together, our genetic and biochemical data
      delineate an essential negative function of E2F4 in cardiac myocyte apoptosis.

PMID- 22985931
TI  - Quantitative proteomics reveals novel functions of osteoclast-associated receptor
      in STAT signaling and cell adhesion in human endothelial cells.
AB  - Previous studies indicate a novel role for the osteoclast-associated receptor
      (OSCAR) in oxidative stress-mediated atherogenesis. However, the functional role
      of OSCAR in endothelial cells is unknown. Here we characterized OSCAR signaling
      in human endothelial cells using a proteomic approach. OSCAR was either
      overexpressed or silenced, and the functional effects were assessed by an in
      depth proteomic study using stable isotope labeling with amino acids in cell
      culture (SILAC). Reduction of complexity using subcellular protein fractions from
      the membrane, the cytosol, and the nucleus of human endothelial cells enabled the
      detection of 4975 unique proteins. Of these proteins, OSCAR overexpression
      regulated 145 and OSCAR silencing regulated 110. These proteins were mainly
      involved in cellular proliferation, inflammatory response and cell-to-cell
      signaling. Interestingly, OSCAR modulation reciprocally regulated signal
      transducer and activator of transcription 1 (STAT1) and 3 (STAT3). Thus, STAT1
      and several interferon-induced proteins showed a clear inverse correlation to
      OSCAR expression, which was further verified by Western blot analysis. In
      contrast, it was found that OSCAR overexpression activated STAT3. Furthermore,
      OSCAR overexpression increased proteins involved in cell adhesion, which
      correlated with an increased adhesion of monocytes to the endothelium after OSCAR
      overexpression. In conclusion, using a comprehensive proteomic approach,
      endothelial cell-derived OSCAR was found to be involved in the STAT signaling
      pathway and to affect monocyte adhesion. This indicates a novel role of OSCAR in
      the vascular-immune cross-talk.

PMID- 22985932
TI  - Orthotopic glioblastoma stem-like cell xenograft model in mice to evaluate intra
      arterial delivery of bevacizumab: from bedside to bench.
AB  - Bevacizumab (BV), a humanized monocolonal antibody directed against vascular
      endothelial growth factor (VEGF), is a standard intravenous (IV) treatment for
      recurrent glioblastoma multiforme (GBM), that has been introduced recently as an
      intra-arterial (IA) treatment modality in humans. Since preclinical models have
      not been reported, we sought to develop a tumor stem cell (TSC) xenograft model
      to investigate IA BV delivery in vivo. Firefly luciferase transduced patient TSC
      were injected into the cortex of 35 nude mice. Tumor growth was monitored weekly
      using bioluminescence imaging. Mice were treated with either intraperitoneal (IP)
      or IA BV, with or without blood-brain barrier disruption (BBBD), or with IP
      saline injection (controls). Tumor tissue was analyzed using immunohistochemistry
      and western blot techniques. Tumor formation occurred in 31 of 35 (89%) mice with
      a significant signal increase over time (p=0.018). Post mortem histology revealed
      an infiltrative growth of TSC xenografts in a similar pattern compared to the
      primary human GBM. Tumor tissue analyzed at 24 hours after treatment revealed
      that IA BV treatment with BBBD led to a significantly higher intratumoral BV
      concentration compared to IA BV alone, IP BV or controls (p<0.05). Thus, we have
      developed a TSC-based xenograft mouse model that allows us to study IA
      chemotherapy. However, further studies are needed to analyze the treatment
      effects after IA BV to assess tumor progression and overall animal survival.

PMID- 22985934
TI  - Dendritic calcium signaling in cerebellar Purkinje cell.
AB  - The Purkinje cells in the cerebellum are unique neurons that generate local and
      global Ca(2+) signals in response to two types of excitatory inputs, parallel
      fiber and climbing fiber, respectively. The spatiotemporal distribution and
      interaction of these synaptic inputs produce complex patterns of Ca(2+) dynamics
      in the Purkinje cell dendrites. The Ca(2+) signals originate from Ca(2+) influx
      through voltage-gated Ca(2+) channels and Ca(2+) release from intracellular
      stores that are mediated by the metabotropic glutamate receptor signaling
      pathway. These Ca(2+) signals are essential for the induction of various forms of
      synaptic plasticity and for controlling the input-output relationship of Purkinje
      cells. In this article we review Ca(2+) signaling in Purkinje cell dendrites. 

PMID- 22985935
TI  - Real-time model learning using Incremental Sparse Spectrum Gaussian Process
      Regression.
AB  - Novel applications in unstructured and non-stationary human environments require
      robots that learn from experience and adapt autonomously to changing conditions.
      Predictive models therefore not only need to be accurate, but should also be
      updated incrementally in real-time and require minimal human intervention.
      Incremental Sparse Spectrum Gaussian Process Regression is an algorithm that is
      targeted specifically for use in this context. Rather than developing a novel
      algorithm from the ground up, the method is based on the thoroughly studied
      Gaussian Process Regression algorithm, therefore ensuring a solid theoretical
      foundation. Non-linearity and a bounded update complexity are achieved
      simultaneously by means of a finite dimensional random feature mapping that
      approximates a kernel function. As a result, the computational cost for each
      update remains constant over time. Finally, algorithmic simplicity and support
      for automated hyperparameter optimization ensures convenience when employed in
      practice. Empirical validation on a number of synthetic and real-life learning
      problems confirms that the performance of Incremental Sparse Spectrum Gaussian
      Process Regression is superior with respect to the popular Locally Weighted
      Projection Regression, while computational requirements are found to be
      significantly lower. The method is therefore particularly suited for learning
      with real-time constraints or when computational resources are limited.

PMID- 22985933
TI  - Post-translational protein modification by O-linked N-acetyl-glucosamine: its
      role in mediating the adverse effects of diabetes on the heart.
AB  - The post-translation attachment of O-linked N-acetylglucosamine, or O-GlcNAc, to
      serine and threonine residues of nuclear and cytoplasmic proteins is increasingly
      recognized as a key regulator of diverse cellular processes. O-GlcNAc synthesis
      is essential for cell survival and it has been shown that acute activation of
      pathways, which increase cellular O-GlcNAc levels is cytoprotective; however,
      prolonged increases in O-GlcNAcylation have been implicated in a number of
      chronic diseases. Glucose metabolism via the hexosamine biosynthesis pathway
      plays a central role in regulating O-GlcNAc synthesis; consequently, sustained
      increases in O-GlcNAc levels have been implicated in glucose toxicity and insulin
      resistance. Studies on the role of O-GlcNAc in regulating cardiomyocyte function
      have grown rapidly over the past decade and there is growing evidence that
      increased O-GlcNAc levels contribute to the adverse effects of diabetes on the
      heart, including impaired contractility, calcium handling, and abnormal stress
      responses. Recent evidence also suggests that O-GlcNAc plays a role in epigenetic
      control of gene transcription. The goal of this review is to provide an overview
      of our current knowledge about the regulation of protein O-GlcNAcylation and to
      explore in more detail O-GlcNAc-mediated responses in the diabetic heart.

PMID- 22985936
TI  - Blood pressure-lowering effect of dietary (-)-epicatechin administration in L
      NAME-treated rats is associated with restored nitric oxide levels.
AB  - Epidemiological and intervention studies have shown that the intake of certain
      chocolates or cocoa products decreases blood pressure (BP) in humans. (-)
      Epicatechin is the most abundant flavanol present in cocoa seeds and its derived
      foods. This work investigates the effects of dietary (-)-epicatechin on BP in
      rats that received N(omega)-nitro-l-arginine methyl ester (L-NAME) for 4 days. (
      )-Epicatechin administration prevented the 42mm Hg increase in BP associated with
      the inhibition of NO production in a dose-dependent manner (0.2-4.0g/kg diet).
      This BP effect was associated with a reduction in L-NAME-mediated increase in the
      indexes of oxidative stress (plasma TBARS and GSSG/GSH(2) ratio) and with a
      restoration of the NO concentration. At the vascular level, none of the
      treatments modified NOS expression, but (-)-epicatechin administration avoided
      the L-NAME-mediated decrease in eNOS activity and increase in both superoxide
      anion production and NOX subunit p47(phox) expression. In summary, (-)
      epicatechin was able to prevent the increase in BP and in oxidative stress and
      restored NO bioavailability. The fact that (-)-epicatechin is present in several
      plants usually consumed by humans gives the possibility of developing diets rich
      in those plants or pharmacological strategies using that flavonoid to diminish BP
      in hypertensive subjects.

PMID- 22985937
TI  - NAD(P)H:quinone oxidoreductase 1 protects bladder epithelium against painful
      bladder syndrome in mice.
AB  - Painful bladder syndrome (PBS), or interstitial cystitis, is a poorly understood
      chronic disease that is characterized by thinning of the bladder epithelium and
      intense pain. Here we demonstrate that NAD(P)H:quinone oxidoreductase 1(-/-)
      (NQO1(-/-)) mice developed in our laboratory represent a new animal model of PBS.
      NQO1 is known to protect against physiological stress as well as protecting
      transcription factors against proteasomal degradation. In this study we
      demonstrate that NQO1 is necessary for bladder epithelium integrity and to
      prevent the development/progression of PBS. We observed downregulation of energy
      metabolism, adhesion, and apoptotic signaling cascades, which led to
      mitochondrial aberrations and profound alterations in energy metabolism,
      increased susceptibility to reactive oxygen species generation, and apoptosis in
      luminal epithelium in NQO1(-/-) mice that were absent in wild-type mice. These
      pathophysiological changes led to the incidence of PBS in NQO1(-/-) mice.
      Altogether, the results demonstrate for the first time that NQO1 is an endogenous
      factor in protection against PBS.

PMID- 22985938
TI  - Protection against peroxynitrite by pseudoperoxidase from Leishmania major.
AB  - Heme proteins share the ability to detoxify reactive nitrogen intermediates (NO
      and peroxynitrite). But, to date, no heme-containing enzymatic defense against
      toxic reactive nitrogen intermediates has been discovered in Leishmania species.
      We have cloned, expressed, and characterized a pseudoperoxidase from Leishmania
      major (LmPP) that is capable of detoxifying peroxynitrite (ONOO(-)). Optical,
      EPR, and resonance Raman spectral studies demonstrate that ONOO(-) can rapidly
      convert the six-coordinate ferric low-spin to a ferric high-spin form at neutral
      pH. Western blotting and immunofluorescence studies with anti-LmPP antibody show
      that the mature enzyme is located at the plasma membrane of amastigotes and is
      expressed eightfold higher in amastigotes compared to promastigotes. Moreover, to
      further investigate its exact physiological role in Leishmania, we have created
      LmPP-knockout mutants by gene replacement in L. major strains. IC(50) values for
      exogenously added H(2)O(2) or 3-morpholinosydnonimine (SIN1) show that deletion
      of LmPP in L. major renders the cell more susceptible to SIN1. The null mutant
      cells exhibit a marked decrease in virulence on infection with activated
      macrophages as well as inoculation into BALB/c mice. Collectively, these data
      provide strong evidence that LmPP plays an important role in the enzymatic
      defense against ONOO(-) within macrophages.

PMID- 22985939
TI  - Expression, purification and analysis of an Arabidopsis recombinant CBL
      interacting protein kinase3 (CIPK3) and its constitutively active form.
AB  - CIPK3 is a member of CBL (calcineurin B-like)-interacting serine-threonine
      protein kinases which play an important role in many developmental and adaptation
      processes in Arabidopsis. Studies conducted on members of this family such as
      SOS2, PKS8 and PKS11 have provided insight into how these kinases interact with
      their target substrates in the signal-response process. Since SOS2, PKS8 and
      PKS11 have low enzymatic activities in vitro and their amino acid sequences are
      homologous to that of CIPK3, it was assumed that CIPK3 would have a low enzymatic
      activity. To enhance CIPK3 enzyme activity, a constitutively active form,
      CIPK3T183D, was generated by a Thr(183) to Asp(183) substitution in the
      activation loop. To obtain proteins for analysis, glutathione S-transferase (GST)
      fusion protein system was used. Although both CIPK3 and CIPK3T183D were
      successfully expressed, they were found in inclusion bodies with three truncated
      proteins. Since the truncated proteins had a similar affinity to the GST-Bind
      Resin as the target protein, the one-step affinity purification could no longer
      be used. As an alternative, His fusion protein expression system was employed for
      protein production. Although both His-CIPK3 and His-CIPK3T183D also accumulated
      in inclusion bodies, they were expressed as a single protein species. A method
      involving Sarkosyl was developed for isolating and purifying the His fusion
      proteins. His-CIPK3 and His-CIPK3T183D produced were highly purified and
      enzymatically active. In addition, a 9-fold increase in kinase activity in His
      CIPK3T183D was observed, indicating that Thr(183) to Asp(183) substitution in the
      activation loop of CIPK3 had succeeded in enhancing the kinase activity.

PMID- 22985941
TI  - Psychosocial characteristics of benzodiazepine addicts compared to not addicted
      benzodiazepine users.
AB  - OBJECTIVE: Although the addictive potential of benzodiazepine drugs has been
      known for a long time, new cases of benzodiazepine addictions keep emerging in
      clinical practice. The etiology of benzodiazepine addiction seems to be
      multifactorial. The objective of this study was to investigate and measure
      psychological and situational factors differentiating benzodiazepine addicts from
      not addicted users. METHODS: A psychological profile and situational factors of
      patients with the diagnosis of benzodiazepine addiction and a carefully matched
      control group of not addicted former benzodiazepine users were defined and
      investigated. RESULTS: The investigated benzodiazepine addicts differed
      significantly from the control group in particular psychological dimensions, such
      as higher neuroticism and introversion, prevalence of emotional rather than task
      based coping mechanisms. There were also significant correlations between the
      addiction and situational factors such as BZD - treatment circumstances and
      adverse life events previous to the treatment. CONCLUSIONS: The results show
      psychological and situational factors which differentiate benzodiazepine addicts
      from not addicted benzodiazepine users. This data suggest that benzodiazepine
      addiction might be associated with higher neuroticism, introversion and less
      effective coping mechanisms as well as with previous accumulation of adverse life
      events and/or inadequate BZD treatment. The psychological and situational factors
      mentioned above might be considered as potential risk factors for benzodiazepine
      addiction.

PMID- 22985940
TI  - Physiologic complexity and aging: implications for physical function and
      rehabilitation.
AB  - The dynamics of most healthy physiological processes are complex, in that they
      are comprised of fluctuations with information-rich structure correlated over
      multiple temporospatial scales. Lipsitz and Goldberger (1992) first proposed that
      the aging process may be characterized by a progressive loss of physiologic
      complexity. We contend that this loss of complexity results in functional decline
      of the organism by diminishing the range of available, adaptive responses to the
      innumerable stressors of everyday life. From this relationship, it follows that
      rehabilitative interventions may be optimized by targeting the complex dynamics
      of human physiology, and by quantifying their effects using tools derived from
      complex systems theory. Here, we first discuss several caveats that one must
      consider when examining the functional and rehabilitative implications of
      physiologic complexity. We then review available evidence regarding the
      relationship between physiologic complexity and system functionality, as well as
      the potential for interventions to restore the complex dynamics that characterize
      healthy physiological function. 

PMID- 22985942
TI  - Laparoscopic ovarian transposition before pelvic radiation in rectal cancer
      patient: safety and feasibility.
AB  - BACKGROUND: Infertility due to pelvic radiation for advanced rectal cancer
      treatment is a major concern particularly in young patients. Pre-radiation
      laparoscopic ovarian transposition may offer preservation of ovarian function
      during the treatment however its use is limited. AIM: The study investigates the
      safety, feasibility and effectiveness of pre-radiation laparoscopic ovarian
      transposition and its effect on ovarian function in the treatment o locally
      advanced rectal cancer. METHODS: Charts review of all young female patients
      diagnosed with locally advanced rectal cancer, underwent laparoscopic ovarian
      transposition, then received preoperative radiotherapy at king Faisal Specialist
      Hospital and Research Centre between 2003-2007. RESULTS: During the period
      studied three single patients age between 21-27 years underwent pre-radiation
      laparoscopic ovarian transposition for advanced rectal cancer. All required
      pretreatment laparoscopic diversion stoma due to rectal stricture secondary to
      tumor that was performed at the same time. One patient died of metastatic disease
      during treatment. The ovarian hormonal levels (FSH and LH) were normal in two
      patients. One has had normal menstrual period and other had amenorrhoea after 4
      months follow-up however her ovarian hormonal level were within normal limits.
      CONCLUSIONS: Laparoscopic ovarian transposition before pelvic radiation in
      advanced rectal cancer treatment is an effective and feasible way of preservation
      of ovarian function in young patients at risk of radiotherapy induced ovarian
      failure. However, this procedure is still under used and it is advisable to
      discuss and propose it to suitable patients.

PMID- 22985943
TI  - Insect symbionts as hidden players in insect-plant interactions.
AB  - There is growing evidence of the importance of microbial mutualistic symbioses in
      insect-plant interactions. Mutualists may affect host plant range and enable
      insects to manipulate plant physiology for their own benefit. The plant can also
      be a route for the horizontal transfer of mutualistic microorganisms among their
      host insects. Where this occurs, selection for improved transmission might cause
      the insect mutualist to damage the plant and become a plant pathogen. Insect
      microbial associates can influence ecological communities by changing the way the
      plant interacts with their hosts' competitors and natural enemies. We review
      recent research in this field and suggest that insect mutualists may be more
      important 'hidden players' in insect-plant interactions than is currently
      realised.

PMID- 22985944
TI  - Reducing multiples: a mathematical formula that accurately predicts rates of
      singletons, twins, and higher-order multiples in women undergoing in vitro
      fertilization.
AB  - OBJECTIVE: To develop a mathematical formula that accurately predicts the
      probability of a singleton, twin, and higher-order multiple pregnancy according
      to implantation rate and number of embryos transferred. DESIGN: A total of 12,003
      IVF cycles from a single center resulting in ET were analyzed. Using mathematical
      modeling we developed a formula, the Combined Formula, and tested for the ability
      of this formula to accurately predict outcomes. SETTING: Academic hospital.
      PATIENT(S): Patients undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Goodness of fit of data from our center and previously published data
      to the Combined Formula and three previous mathematical models. RESULT(S): The
      Combined Formula predicted the probability of singleton, twin, and higher-order
      pregnancies more accurately than three previous formulas (1.4% vs. 2.88%, 4.02%,
      and 5%, respectively) and accurately predicted outcomes from five previously
      published studies from other centers. An online applet is provided
      (https://secure.ivf.org/ivf-calculator.html). CONCLUSION(S): The probability of
      pregnancy with singletons, twins, and higher-order multiples according to number
      of embryos transferred is predictable and not random and can be accurately
      modeled using the Combined Formula. The embryo itself is the major predictor of
      pregnancy outcomes, but there is an influence from "barriers," such as the
      endometrium and collaboration between embryos (embryo-embryo interaction). This
      model can be used to guide the decision regarding number of embryos to transfer
      after IVF.

PMID- 22985946
TI  - Hepatotoxicity with flutamide.

PMID- 22985947
TI  - Adipose tissue insulin resistance in peripubertal girls with first-degree family
      history of polycystic ovary syndrome.
AB  - OBJECTIVE: To assess metabolic and endocrine defects in girls genetically
      predisposed to polycystic ovary syndrome (PCOS). DESIGN: Controlled cross
      sectional study. SETTING: University hospital. PATIENT(S): Nine girls, aged 8-14
      years, having a first-degree relative diagnosed with PCOS (PCOSr) and 10 age
      matched girls without a family history of PCOS. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Insulin sensitivity (IS(FSIVGTT)) determined by frequently
      sampled IV glucose tolerance testing (GTT) and insulin-induced nonesterified
      fatty acid (NEFA) suppression, estimated by the log-linear slope of NEFA levels
      during the first 20 minutes of GTT. RESULT(S): In comparison to controls, PCOSr
      had higher body mass index (BMI) Z-score, waist circumference, and waist-to
      height ratio. Levels of the androgen 17alpha-hydroxyprogesterone (17-OHP) were
      significantly increased in PCOSr, independent of adiposity, and inversely
      correlated with IS(FSIVGTT). The IS(FSIVGTT) was decreased and the NEFA
      suppression was less steep in PCOSr compared with controls, independent of BMI
      and 17-OHP. The NEFA suppression was more pronounced with increasing IS(FSIVGTT),
      independent of adiposity. CONCLUSION(S): Girls at high risk of developing PCOS
      display increased adiposity and 17-OHP levels, but are mainly characterized by
      global insulin resistance and resistance to insulin-induced suppression of
      lipolysis that were independent of adiposity and 17-OHP levels. Therefore,
      genetic predisposition to PCOS may be related to early insulin resistance and
      adipocyte dysfunction.

PMID- 22985948
TI  - Defective protein kinase A and C pathways are common causes of disordered zona
      pellucida (ZP)--induced acrosome reaction in normozoospermic infertile men with
      normal sperm-ZP binding.
AB  - OBJECTIVE: To determine association between defective protein kinases C (PKC) and
      A (PKA) and disordered zona pellucida (ZP)-induced acrosome reaction (DZPIAR) in
      normozoospermic infertile men with normal sperm-ZP binding. DESIGN: Sperm from
      DZPIAR infertile men were treated without (control) or with (test) phorbol
      myristate acetate (PMA, PKC activator) or dibutyryl cyclic AMP (dbcAMP, PKA
      activator) under in vitro standard culture condition. The ZP-induced AR was
      assessed and compared between control and test. SETTING: Public and private
      hospital-based clinical assisted reproduction technology (ART) centers.
      PATIENT(S): A total of 51 DZPIAR infertile men were involved in this study.
      INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Sperm-ZP binding and the ZP
      induced IAR. RESULT(S): Both PMA and dbcAMP enhanced ZP-induced AR up to a normal
      level (>=25%) in some subjects with DZPIAR: 29 (57%) with PMA and 27 (53%) with
      dbcAMP. Overall 35 (69%) had the ZP-induced AR enhanced to normal by PMA or
      dbcAMP but 16 (31%) had little or no response to either agent. Fourteen men
      responded to the two activators differently: 8 effective only with PMA and 6
      effective only with dbcAMP. CONCLUSION(S): Defective upstream of PKC and PKA
      pathways are highly associated with disordered ZPIAR in normozoospermic infertile
      men with normal sperm-ZP binding.

PMID- 22985949
TI  - G-protein beta3 subunit gene 825C/T polymorphism and its association with the
      presence, severity, and duration of vasculogenic erectile dysfunction.
AB  - OBJECTIVE: To investigate the association between G-protein beta3 (GNB3) subunit
      gene 825C/T polymorphism and vasculogenic ED (VED). DESIGN: Case-control study.
      SETTING: Private urology and andrology clinic. PATIENT(S): The study included 246
      patients with VED and 492 healthy controls, Caucasians of Iranian descent.
      INTERVENTION(S): Typing of the polymorphism was performed using the polymerase
      chain reaction restriction fragment length polymorphism technique. MAIN OUTCOME
      MEASURE(S): To test the hypothesis of whether the presence of the 825T allele of
      the GNB3 gene is associated with an increased risk of VED. RESULT(S): The CT
      genotype was more prevalent in VED patients relative to healthy controls
      (adjusted odds ratio [OR] = 2.34; 95% confidence interval [CI], 1.10-4.26).
      Interaction between T allele carriership and VED was significant. The dominant
      model CT + TT variant was associated with a 3.74-fold increase in the adjusted
      risk (OR = 3.74; 95% CI, 1.11-12.4) for the occurrence of VED. Our results
      indicate that the GNB3 polymorphism is associated with higher systolic blood
      pressure, higher dyslipidemia, and higher body mass index. The 825TT genotype was
      associated with a more than five-fold increased risk of severe VED compared with
      the 825CC genotype (OR = 5.62; 95% CI, 3.54-9.25). Significantly different onset
      of age of VED was not found between the genotypes for the GNB3 polymorphism.
      CONCLUSION(S): The GNB3 polymorphism is an independent risk factor for VED in
      Iranian males. Our findings confirm a role of GNB3 in the genetic susceptibility
      of VED and suggest that GNB3 polymorphism should be taken into consideration to
      improve the assessment of an individual's risk of VED.

PMID- 22985950
TI  - A common Asn680Ser polymorphism in the follicle-stimulating hormone receptor gene
      is not associated with ovarian response to gonadotropin stimulation in patients
      undergoing in vitro fertilization.
AB  - OBJECTIVE: To assess the role of the variant p.Asn680Ser in the follicle
      stimulating hormone receptor (FSHR) gene in determining ovarian response in
      patients undergoing in vitro fertilization (IVF) treatment. DESIGN: Prospective
      observational study. SETTING: Tertiary referral center for reproductive medicine.
      PATIENT(S): Women (n = 421) undergoing their first cycle of controlled ovarian
      stimulation for IVF and 83 healthy, ethnically matched controls. INTERVENTION(S):
      Baseline pelvic ultrasound and blood tests taken on days 2 to 3 of the cycle for
      assessment of baseline hormones and for DNA extraction. MAIN OUTCOME MEASURE(S):
      Genotypes for FSHR p.Asn680Ser determined using TaqMan allelic discrimination
      assay, and ovarian response to gonadotropin treatment classified as normal, poor,
      or overresponse based on the number of oocytes retrieved. RESULT(S): The FSHR
      p.Asn680Ser genotype frequencies were similar in IVF patients and controls. The
      number of oocytes retrieved was comparable between patients with different FSHR
      receptor genotypes. The total amount of gonadotropin used was also similar in all
      the genotype groups. A logistic regression analysis showed nonstatistically
      significant twofold difference in the distribution of genotypes between the
      groups with poor and normal ovarian response. CONCLUSION(S): The variant FSHR
      p.Asn680Ser was not shown to be predictive of ovarian response, but clinically
      relevant differences cannot be ruled out.

PMID- 22985951
TI  - Attractiveness of women with rectovaginal endometriosis: a case-control study.
AB  - OBJECTIVE: To evaluate physical attractiveness in women with and without
      endometriosis. DESIGN: Case-control study. SETTING: Academic hospital.
      PATIENT(S): Three hundred nulliparous women. INTERVENTION(S): Assessment of
      attractiveness by four independent female and male observers. MAIN OUTCOME
      MEASURE(S): A graded attractiveness rating scale. RESULT(S): A total of 31 of 100
      women in the rectovaginal endometriosis group (cases) were judged as attractive
      or very attractive, compared with 8 of 100 in the peritoneal and ovarian
      endometriosis group and 9 of 100 in the group of subjects without endometriosis.
      A higher proportion of cases first had intercourse before age 18 (53%, 39%, and
      30%, respectively). The mean +/- SD body mass index in women with rectovaginal
      endometriosis, in those with other disease forms, and in those without
      endometriosis was, respectively, 21.0 +/- 2.5, 21.3 +/- 3.3, and 22.1 +/- 3.6.
      The median (interquartile range) waist-to-hip ratio and breast-to-underbreast
      ratio were, respectively, 0.75 (0.71-0.81), 0.76 (0.71-0.81), and 0.78 (0.73
      0.83), and 1.15 (1.12-1.20), 1.14 (1.10-1.17), and 1.15 (1.11-1.18).
      CONCLUSION(S): Women with rectovaginal endometriosis were judged to be more
      attractive than those in the two control groups. Moreover, they had a leaner
      silhouette, larger breasts, and an earlier coitarche.

PMID- 22985952
TI  - Neuropsychological performance of native versus non-native English speakers.
AB  - Relatively little is known about differences in English-administered, clinical
      neuropsychological test performance between native versus non-native English
      speakers, with prior literature yielding mixed findings. The purpose of this
      study was to examine the performance of native and non-native English speakers
      with similar age and educational backgrounds on a variety of cognitive tests.
      Participants were 153 university students (115 native and 38 non-native English
      speakers) who completed a neuropsychological battery during two testing sessions.
      Multiple regression analyses examined relations of native language to cognitive
      performance after adjustment for age, education, sex, and depressive
      symptomatology. Results showed that native English speakers outperformed non
      native English speakers on several language-mediated tasks-Letter and Category
      Fluency and the Cognitive Estimation Test-as well as Trails A (p's < .05). The
      two groups performed similarly on tests of executive functions, perceptuo-motor
      speed, verbal memory, and visuospatial abilities. These results suggest that non
      native English language may have a negative influence predominantly on language
      dependent tasks.

PMID- 22985953
TI  - Ultrasonic treatment and synthesis of sugar alcohol modified Na+-montmorillonite
      clay.
AB  - Na(+)-montmorillonite clay (generally referred to as MMT) is very useful for
      reinforcing polymeric matrix at very low concentrations (typically, 2-5% wt).
      These clay particles are typically exfoliated before they can demonstrate the
      significant gains in heat deflection temperature, modulus, and elongation
      properties. In the case of hydrophilic biopolymer based matrices, such as
      carbohydrates and chitosan, exfoliating these nanoclay particles needs greater
      attention because the exfoliation is typically carried out using hydrophobic
      oligomers through ion-exchange. This study reports a new method of synthesizing
      completely hydrophilic MMT-assemblages using hydrophilic plasticizers for
      biopolymers. We used sugar alcohols (glycerol, xylitol with 3 and 5 hydroxyl
      groups) and polysaccharide maltodextrin to exfoliate the MMT. Sonication was
      conducted for MMT nanoclay and plasticizers at different weight ratios. It was
      confirmed that all plasticizer/modifier led to expansion of MMT gallery spacing
      (d-spacing) and the change in d-spacing could be related to the molecular
      structure of the plasticizer. Meanwhile, the extent of exfoliation was maximum
      with maltodextrin (fully exfoliation with 1:10 and 1:20 ratio of MMT:plasticizer)
      across all test samples and interestingly, glycerol and xylitol samples quickly
      established within the MMT galleries and exhibited minimal influence with further
      increase in relative concentrations.

PMID- 22985954
TI  - The clinical effectiveness and cost-effectiveness of technologies used to
      visualise the seizure focus in people with refractory epilepsy being considered
      for surgery: a systematic review and decision-analytical model.
AB  - BACKGROUND: For patients who continue to have seizures despite ongoing treatment,
      surgical resection of the epileptic focus may be considered, and can result in
      seizure-freedom. Currently, non-invasive tests provide information to inform the
      scope and positioning of invasive electroencephalography (EEG) electrodes.
      However, these technologies could replace intracranial EEG in at least some
      patients if their ability to accurately locate a seizure focus could be
      established. In order to inform clinical practice, studies need to investigate
      the clinical value of a test, and the impact of the results of that test on the
      decision-making process and subsequently on clinical outcomes. OBJECTIVES: The
      aims of this systematic review were to determine the diagnostic accuracy of non
      invasive technologies, how these technologies impact on the decision-making
      process, associations with surgical outcome, and the gaps in the current evidence
      base. In addition, a decision-analytical model was designed to consider the
      potential use of existing data to determine the cost-effectiveness of options for
      presurgical work-up. DATA SOURCES: Eighteen electronic databases were searched
      without language restrictions [including MEDLINE, EMBASE, BIOSIS Previews,
      PASCAL, ClinicalTrials.gov, Cochrane Database of Systematic Reviews (CDSR),
      Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane
      Register of Diagnostic Studies] from 2003 to July 2010. A prior, wider-ranging
      HTA review in this area conducted by the Centre for Reviews and Dissemination was
      used as the source for studies prior to 2003. Reference lists of included studies
      and relevant reviews were also searched, and a citation search of key papers
      undertaken. REVIEW METHODS: Systematic reviews of the diagnostic accuracy,
      clinical utility and cost-effectiveness of non-invasive technologies used to
      define the seizure focus in patients with refractory epilepsy being considered
      for surgery were undertaken according to the PRISMA (Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses) guidelines. Thirteen diagnostic
      accuracy studies, seven outcome prediction studies and one study reporting the
      impact of test results on the decision-making process ('decision study') were
      included. The decision study was used to aid the development of a decision
      analytical model to illustrate how data from appropriately designed clinical
      studies can be utilised. RESULTS: Data from the diagnostic accuracy studies could
      not determine the contribution of the tests to the decision-making process. The
      number of index tests that could not be classified as correctly, non- or wrongly
      localising as indicated by a surgical outcome was high, up to 53%. The decision
      study reported fluorodeoxyglucose positron emission tomography influencing the
      decision for or against surgery in 78 of the 110 patients. The constructed
      decision-analytical model provided provisional cost-effectiveness results from
      the included diagnostic strategies. It demonstrated the feasibility of extending
      such analysis to all diagnostic strategies if suitable data were to become
      available. LIMITATIONS: There were a number of limitations of the available
      evidence, and overall, the quality of the available evidence was poor; only one
      study met the inclusion criteria that evaluated the use an index test on the
      decision-making process. Most of the available data was from the diagnostic
      accuracy studies; those currently available did not provide information on either
      the diagnostic accuracy or clinical utility of the tests being evaluated. Further
      limitations were the generally small study sizes, patient selection bias and the
      substantial clinical heterogeneity across the studies. CONCLUSIONS: The current
      evidence base is abundant but not adequately informative; there is no acceptable
      reference standard, reporting of clinical outcomes tends to be only following
      surgery, and decision level and clinical effectiveness studies are lacking. The
      additional value of diagnostic technologies for the localisation of epileptic
      foci is related to the impact on treatment decisions and the value of the
      treatments themselves; this needs to be considered fully in informing cost
      effectiveness. Appropriately designed studies are needed to determine the added
      value of diagnostic regimens. Ultimately, how research informs the actual
      decision problem(s) faced by clinicians and the NHS needs to be considered;
      decision modelling is central to this issue. FUNDING: The National Institute for
      Health Research Health Technology Assessment programme.

PMID- 22985955
TI  - Effects of different nitrate and phosphate concentrations on the growth and toxin
      production of an Alexandrium tamarense strain collected from Drake Passage.
AB  - Nitrate (N) and phosphate (P) are believed to be two of the most important
      nutrients for the growth and toxin production for Alexandrium species. The study
      of the growth and toxicity characteristics of the Alexandrium spp. under the
      change of N and P can help us to understand the dynamics of algal bloom and
      toxification events in natural environments. A strain of Alexandrium tamarense
      (designated as Kci) was successfully isolated from the Drake Passage in 2001 and
      the clonal culture has been kept in our laboratory (Ho et al., 2003, 2012). In
      order to extend our understanding on the growth physiology and toxicity of this
      A. tamarense strain, growth and cellular toxin content were examined in unialgal
      batch cultures under different concentrations of N and P. The effects of variable
      N, P concentrations on growth, cellular toxicity (fg STXeq. cell(-1)), and toxin
      composition (% molar) were determined in both exponential and stationary growth
      phases. The toxin profile, determined by high-performance liquid chromatography
      with fluorescence detection (HPLC-FD), was found to be remained relatively stable
      and was consistently dominated by the N-sulfocarbamoyl C-toxins (>90%) under
      different conditions and growth phases. There were also trace amounts of other
      carbamate gonyautoxins consistently expressed. The cellular toxicity varied under
      different N and P concentrations, as well as different growth stages. A positive
      correlation was observed between cellular toxicity and N concentrations, but the
      toxicity was enhanced when P was depleted. Both cell densities and growth rate of
      the cells were severely suppressed under N- or P-depletion. However, the
      biovolume of the cells tended to be larger at N- or P-depleted cultures. Results
      from the present study provide valuable insight for the ecophysiology of
      Alexandrium species in the coastal ecosystem of Drake Passage.

PMID- 22985957
TI  - Synthesis, biological evaluation of novel 4,5-dihydro-2H-pyrazole 2-hydroxyphenyl
      derivatives as BRAF inhibitors.
AB  - A series of novel 4,5-dihydropyrazole derivatives (3a-3t) containing
      hydroxyphenyl moiety as potential V600E mutant BRAF kinase (BRAF(V600E))
      inhibitors were designed and synthesized. Docking simulation was performed to
      insert compounds 3d (1-(5-(5-chloro-2-hydroxyphenyl)-3-(p-tolyl)-4,5-dihydro-1H
      pyrazol-1-yl)ethanone) and 3m (1-(3-(4-chlorophenyl)-5-(3,5-dibromo-2
      hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) into the crystal structure
      of BRAF(V600E) to determine the probable binding model, respectively. Based on
      the preliminary results, compound 3d and 3m with potent inhibitory activity in
      tumor growth may be a potential anticancer agent. Results of the bioassays
      against BRAF(V600E), MCF-7 human breast cancer cell line and WM266.4 human
      melanoma cell line all showed several compounds had potent activities IC(50)
      value in low micromolar range, among them, compound 3d and compound 3m showed
      strong potent anticancer activity, which were proved by that 3d: IC(50) = 1.31
      MUM for MCF-7 and IC(50) = 0.45 MUM for WM266.5, IC(50) = 0.22 MUM for
      BRAF(V600E), 3m: IC(50) = 0.97 MUM for MCF-7 and IC(50) = 0.72 MUM for WM266.5,
      IC(50) = 0.46 MUM for BRAF(V600E), which were comparable with the positive
      control Erlotinib.

PMID- 22985958
TI  - Potent small molecule Hedgehog agonists induce VEGF expression in vitro.
AB  - Here, we describe the synthesis, SAR studies as well as biological investigations
      of the known Hedgehog signaling agonist SAG and a small library of its analogues.
      The SAG and its derivatives were analyzed for their potency to activate the
      expression of the Hh target gene Gli1 in a reporter gene assay. By analyzing SAR
      important molecular descriptors for Gli1 activation have been identified. SAG as
      well as compound 10c proven to be potent activators of VEGF expression in
      cultivated dermal fibroblasts. Importantly and in contrast to SAG, derivative 10c
      displayed no toxicity in concentrations up to 250 MUm.

PMID- 22985956
TI  - Insights towards sulfonamide drug specificity in alpha-carbonic anhydrases.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are a group of metalloenzymes that play
      important roles in carbon metabolism, pH regulation, CO2 fixation in plants, ion
      transport etc., and are found in all eukaryotic and many microbial organisms.
      This family of enzymes catalyzes the interconversion of CO2 and HCO3(-). There
      are at least 16 different CA isoforms in the alpha structural class (alpha-CAs)
      that have been isolated in higher vertebrates, with CA isoform II (CA II) being
      ubiquitously abundant in all human cell types. CA inhibition has been exploited
      clinically for decades for various classes of diuretics and anti-glaucoma
      treatment. The characterization of the overexpression of CA isoform IX (CA IX) in
      certain tumors has raised interest in CA IX as a diagnostic marker and drug
      target for aggressive cancers and therefore the development of CA IX specific
      inhibitors. An important goal in the field of CA is to identify, rationalize, and
      design potential compounds that will preferentially inhibit CA IX over all other
      isoforms of CA. The variations in the active sites between isoforms of CA are
      subtle and this causes non-specific CA inhibition which leads to various side
      effects. In the case of CA IX inhibition, CA II along with other isoforms of CA
      provide off-target binding sites which is undesirable for cancer treatment. The
      focus of this article is on CA IX inhibition and two different structural
      approaches to CA isoform specific drug designing: tail approach and fragment
      addition approach.

PMID- 22985960
TI  - Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4
      dione scaffolds as submicromolar inhibitors of HAT.
AB  - A library of 1,4-benzodiazepines has been synthesised and evaluated for activity
      against Trypanosoma brucei, a causative parasite of Human African Trypanosomiasis
      (HAT). The most potent of these derivatives has an MIC value of 0.97 MUM. Herein
      we report the design, synthesis and biological evaluation of the abovementioned
      compounds.

PMID- 22985959
TI  - Selection, synthesis, and anti-inflammatory evaluation of the arylidene malonate
      derivatives as TLR4 signaling inhibitors.
AB  - Inhibition of TLR4 signaling is an important therapeutic strategy for
      intervention in the etiology of several pro-inflammatory diseases. There has been
      intensive research in recent years aiming to explore this strategy, and identify
      small molecule inhibitors of the TLR4 pathway. However, the recent failure of a
      number of advanced drug candidates targeting TLR4 signaling (e.g., TAK242 and
      Eritoran) prompted us to continue the search for novel chemical scaffolds to
      inhibit this critical inflammatory response pathway. Here we report the
      identification of a group of new TLR4 signaling inhibitors through a cell-based
      screening. A series of arylidene malonate analogs were synthesized and assayed in
      murine macrophages for their inhibitory activity against LPS-induced nitric oxide
      (NO) production. The lead compound 1 (NCI126224) was found to suppress LPS
      induced production of nuclear factor-kappaB (NF-kappaB), tumor necrosis factor
      (TNF-alpha), interleukin-1beta (IL-1beta), and nitric oxide (NO) in the nanomolar
      low micromolar range. Taken together, this study demonstrates that 1 is a
      promising potential therapeutic candidate for various inflammatory diseases.

PMID- 22985961
TI  - Synthesis and pharmacological investigation of azaphthalazinone human histamine
      H(1) receptor antagonists.
AB  - 5-Aza, 6-aza, 7-aza and 8-aza-phthalazinone, and 5,8-diazaphthalazinone templates
      were synthesised by stereoselective routes starting from the appropriate
      pyridine/pyrazine dicarboxylic acids by activation with CDI, reaction with 4
      chlorophenyl acetate ester enolate to give a beta-ketoester, which was
      hydrolysed, and decarboxylated. The resulting ketone was condensed with hydrazine
      to form the azaphthalazinone core. The azaphthalazinone cores were alkylated with
      N-Boc-D-prolinol at N-2 by Mitsunobu reaction, de-protected, and then alkylated
      at the pyrrolidine nitrogen to provide the target H(1) receptor antagonists. All
      four mono-azaphthalazinone series had higher affinity (pK(i)) for the human H(1)
      receptor than azelastine, but were not as potent as the parent non-aza
      phthalazinone. The 5,8-diazaphthalazinone was equipotent with azelastine. The
      least potent series were the 7-azaphthalazinones, whereas the 5-azaphthalazinones
      were the most lipophilic. The more hydrophilic series were the 8-aza series.
      Replacement of the N-methyl substituent on the pyrrolidine with the n-butyl group
      caused an increase in potency (pA(2)) and a corresponding increase in
      lipophilicity. Introduction of a beta-ether oxygen in the n-butyl analogues (2
      methoxyethyl group) decreased the H(1) pA(2) slightly, and increased the
      selectivity against hERG. The duration of action in vitro was longer in the 6
      azaphthalazinone series. The more potent and selective 6-azaphthalazinone core
      was used to append an H(3) receptor antagonist fragment, and to convert the
      series into the long acting single-ligand, dual H(1) H(3) receptor antagonist 44.
      The pharmacological profile of 44 was very similar to our intranasal clinical
      candidate 1.

PMID- 22985962
TI  - Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4]dioxin
      containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase.
AB  - Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H
      pyrazole derivatives C1-C15 and D1-D15 have been synthesized and evaluated for
      their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4
      bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3
      dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological
      activity against B-Raf(V600E) (IC(50) = 0.11 MUM) and WM266.4 human melanoma cell
      line (GI(50) = 0.58 MUM), being comparable with the positive control Erlotinib
      and more potent than our previous best compound, while D10 ((2,3
      dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3-fluorophenyl)-3-phenyl-4,5-dihydro-1H
      pyrazol-1-yl)methanone) performed the best in the D series (IC(50) = 1.70 MUM;
      GI(50) = 1.45 MUM). The docking simulation was performed to analyze the probable
      binding models and poses and the QSAR model was built for reasonable design of B
      Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin
      structure reinforced the combination of our compounds and the receptor, resulting
      in progress of bioactivity.

PMID- 22985963
TI  - Synthesis and antiviral activity of 4,6-disubstituted pyrimido[4,5-b]indole
      ribonucleosides.
AB  - A series of new pyrimido[4,5-b]indole ribonucleosides bearing phenyl or hetaryl
      group at position 4 has been prepared by selective Pd-catalyzed cross-coupling
      reactions of the corresponding protected 4,6-dichloropyrimido[4,5-b]indole
      ribonucleoside with (het)arylboronic acids or stannanes followed by deprotection.
      Further cross-couplings under harsher conditions and employing X-Phos ligand
      proceeded at the position 6 leading to 4,6-disubstituted pyrimido[4,5-b]indole
      ribonucleosides. Some of these compounds displayed antiviral activity against
      Dengue virus.

PMID- 22985964
TI  - Designed Armadillo repeat proteins: library generation, characterization and
      selection of peptide binders with high specificity.
AB  - Designed Armadillo repeat proteins (ArmRPs) are a novel class of binding proteins
      intended for general modular peptide binding and have very favorable expression
      and stability properties. Using a combination of sequence and structural
      consensus analyses, we generated a 42-amino-acid designed Armadillo repeat module
      with six randomized positions, having a theoretical diversity of 9.9*10(6) per
      repeat. Structural considerations were used to replace cysteine residues, to
      define less conserved positions and to decide where to introduce randomized amino
      acid residues for potential interactions with the target peptide. Based on these
      concepts, combinatorial libraries of designed ArmRPs were assembled. The most
      stable version of designed ArmRP in library format was the N5C format, with three
      randomized library repeat modules flanked by full consensus repeat modules on
      either side and, in turn, flanked by N- and C-terminal capping repeats.
      Unselected members of this library were well expressed in the Escherichia coli
      cytoplasm, monomeric and showed the expected CD spectra and cooperative
      unfolding. N5C libraries were used in ribosome display selections against the
      peptide neurotensin. Highly specific peptide binders were enriched after four
      rounds of selections using ribosome display. Four peptide side chains were shown
      to contribute most of the interaction energy, and single alanine mutants could be
      discriminated. Thus, designed ArmRP libraries can become valuable sources for
      peptide binding molecules because of their favorable biophysical properties and
      with a potential for application in general modular peptide recognition.

PMID- 22985965
TI  - Biosynthesis of the 22nd genetically encoded amino acid pyrrolysine: structure
      and reaction mechanism of PylC at 1.5A resolution.
AB  - The second step in the biosynthesis of the 22nd genetically encoded amino acid
      pyrrolysine (Pyl) is catalyzed by PylC that forms the pseudopeptide L-lysine
      N(epsilon)-3R-methyl-D-ornithine. Here, we present six crystal structures of the
      monomeric active ligase in complex with substrates, reaction intermediates, and
      products including ATP, the non-hydrolyzable ATP analogue 5'-adenylyl-beta-gamma
      imidodiphosphate, ADP, D-ornithine (D-Orn), L-lysine (Lys), phosphorylated D-Orn,
      L-lysine-N(epsilon)-D-ornithine, inorganic phosphate, carbonate, and Mg(2+). The
      overall structure of PylC reveals similarities to the superfamily of ATP-grasp
      enzymes; however, there exist unique structural and functional features for a
      topological control of successive substrate entry and product release.
      Furthermore, the presented high-resolution structures provide detailed insights
      into the reaction mechanism of isopeptide bond formation starting with
      phosphorylation of D-Orn by transfer of a phosphate moiety from activated ATP.
      The binding of Lys to the enzyme complex is then followed by an S(N)2 reaction
      resulting in L-lysine-N(epsilon)-D-ornithine and inorganic phosphate.
      Surprisingly, PylC harbors two adenine nucleotides bound at the active site, what
      has not been observed in any ATP-grasp protein analyzed to date. Whereas one ATP
      molecule is involved in catalysis, the second adenine nucleotide functions as a
      selective anchor for the C- and N-terminus of the Lys substrate and is
      responsible for protein stability as shown by mutagenesis.

PMID- 22985967
TI  - Disulfide biochemistry in 2-cys peroxiredoxin: requirement of Glu50 and Arg146
      for the reduction of yeast Tsa1 by thioredoxin.
AB  - 2-Cys peroxiredoxin (Prx) enzymes are ubiquitously distributed peroxidases that
      make use of a peroxidatic cysteine (Cys(P)) to decompose hydroperoxides. A
      disulfide bond is generated as a consequence of the partial unfolding of the
      alpha-helix that contains Cys(P). Therefore, during its catalytic cycle, 2-Cys
      Prx alternates between two states, locally unfolded and fully folded. Tsa1 (thiol
      specific antioxidant protein 1 from yeast) is by far the most abundant Cys-based
      peroxidase in Saccharomyces cerevisiae. In this work, we present the
      crystallographic structure at 2.8A resolution of Tsa1(C47S) in the decameric form
      [(alpha(2))(5)] with a DTT molecule bound to the active site, representing one of
      the few available reports of a 2-Cys Prx (AhpC-Prx1 subfamily) (AhpC, alkyl
      hydroperoxide reductase subunit C) structure that incorporates a ligand. The
      analysis of the Tsa1(C47S) structure indicated that Glu50 and Arg146 participate
      in the stabilization of the Cys(P) alpha-helix. As a consequence, we raised the
      hypothesis that Glu50 and Arg146 might be relevant to the Cys(P) reactivity.
      Therefore, Tsa1(E50A) and Tsa1(R146Q) mutants were generated and were still able
      to decompose hydrogen peroxide, presenting a second-order rate constant in the
      range of 10(6)M(-1)s(-1). Remarkably, although Tsa1(E50A) and Tsa1(R146Q) were
      efficiently reduced by the low-molecular-weight reductant DTT, these mutants
      displayed only marginal thioredoxin (Trx)-dependent peroxidase activity,
      indicating that Glu50 and Arg146 are important for the Tsa1-Trx interaction.
      These results may impact the comprehension of downstream events of signaling
      pathways that are triggered by the oxidation of critical Cys residues, such as
      Trx.

PMID- 22985966
TI  - Directed evolution of the forkhead-associated domain to generate anti
      phosphospecific reagents by phage display.
AB  - While affinity reagents are valuable tools for monitoring protein phosphorylation
      and studying signaling events in cells, generating them through immunization of
      animals with phosphopeptides is expensive, laborious, and time-consuming. An
      attractive alternative is to use protein evolution techniques and isolate new
      anti-phosphopeptide binding specificities from a library of variants of a
      phosphopeptide-binding domain. To explore this strategy, we attempted to display
      on the surface of bacteriophage M13 the N-terminal Forkhead-associated (FHA1)
      domain of yeast Rad53p, which is a naturally occurring phosphothreonine (pT)
      binding domain, and found it to be nonfunctional due to misfolding in the
      bacterial periplasm. To overcome this limitation, we constructed a library of
      FHA1 variants by mutagenic PCR and isolated functional variants after three
      rounds of affinity selection with its pT peptide ligand. A hydrophobic residue at
      position 34 in the beta1 strand was discovered to be essential for phage display
      of a functional FHA1 domain. Additionally, by heating the phage library to 50
      degrees C prior to affinity selection with its cognate pT peptide, we identified
      a variant (G2) that was ~8 degrees C more thermally stable than the wild-type
      domain. Using G2 as a scaffold, we constructed phage-displayed libraries of FHA1
      variants and affinity selected for variants that bound selectively to five pT
      peptides. These reagents are renewable and have high protein yields (~20-25mg/L),
      when expressed in Escherichia coli. Thus, we have changed the specificity of the
      FHA1 domain and demonstrated that engineering phosphopeptide-binding domains is
      an attractive avenue for generating new anti-phosphopeptide binding specificities
      in vitro by phage display.

PMID- 22985968
TI  - WITHDRAWN: Tetravalent Bispecific Single-Chain Fv Antibodies for Lysis of
      Leukemia Cells by Autologous T Cells.
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- 22985969
TI  - Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced
      primary and secondary hypersensitivity in rats.
AB  - GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in
      animal models of pathological pain, in part via enhancing injury-induced loss of
      GABA-A-alpha2 and -alpha3 receptor function within the spinal cord. As yet, a
      lack of clinically suitable tool compounds has prevented this concept being
      tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a
      human volunteer pain model we have compared compounds capable of variously
      modulating GABA-A receptor function in comparable rat models of capsaicin-induced
      acute nocifensive flinching behaviour and secondary mechanical hypersensitivity.
      The subtype-selective PAM NS11394 (0.3-10 mg/kg), and the non-selective PAM
      diazepam (1-5 mg/kg) variously reduced capsaicin-induced secondary mechanical
      hypersensitivity (180 min post-injection). However, the low efficacy subtype
      selective PAM TPA023 (3-30 mg/kg) was completely ineffective. This was surprising
      as both NS11394 and TPA023 robustly attenuated late phase (6-30 min post
      injection) capsaicin-induced flinching, a pain-like behaviour that is putatively
      driven by peripheral and central sensitizing mechanisms. Diazepam also attenuated
      capsaicin-induced nocifensive behaviours, albeit at doses previously shown to
      impair locomotor function. Our data indicate that GABA-A receptor PAMs with
      optimal selectivity and efficacy profiles reduce centrally-mediated mechanical
      hypersensitivity in capsaicin-injected rats, an observation that we expect can
      translate directly to human volunteer studies.

PMID- 22985970
TI  - Upregulation of amino acid transporter expression induced by L-leucine
      availability in L6 myotubes is associated with ATF4 signaling through mTORC1
      dependent mechanism.
AB  - OBJECTIVE: Essential amino acids, especially l-leucine, initiate the signaling of
      the mammalian target of rapamycin complex-1 (mTORC1) and protein synthesis in
      skeletal muscle. Current information on the relation between amino acid
      transporter mechanisms and mTORC1 signaling is sparse. The objectives of this
      study were to determine whether an increase in leucine availability upregulates
      the gene transcription and translation of amino acid transporters and other amino
      acid members in an mTORC1-dependent pathway that control amino acid use (general
      control non-repressed-2 and activating transcription factor-4) and to measure the
      factors related to protein synthesis and proteolysis. METHODS: L6 skeletal muscle
      cells that had been treated with l-leucine (0.105 g/L) were incubated for 30 min
      to stimulate the transcription of L-type amino acid transporter-1, CD98, and
      sodium-coupled neutral amino acid transporter-2 and increase activating
      transcription factor-4 protein, which is dependent on the mTORC1 signaling
      pathway. RESULTS: A rapid, high level of p70 S6 kinase-1 phosphorylation was
      detected but was suppressed by rapamycin (P < 0.05). The addition of leucine
      decreased the atrogin-1 transcription abundance in an insulin-involved manner (P
      < 0.05), which could not be completely blocked by rapamycin (P = 0.055).
      CONCLUSIONS: Our findings indicate that the mTOR is a component of the nutrient
      signaling pathway, which regulates system A and L amino acid transporters, the
      initiation factors involved in mRNA translation, and is downstream of forkhead
      box-O in L6 myotubes.

PMID- 22985971
TI  - META060 protects against diet-induced obesity and insulin resistance in a high
      fat-diet fed mouse.
AB  - OBJECTIVE: We investigated whether a reduced iso-alpha acid derived from an
      extract of Humulus lupulus L., META060, had an effect on weight gain, body
      composition, and metabolism in a high-fat-diet (HFD) fed mouse model. METHODS:
      Weight gain was monitored for up to 20 wk in mice receiving a low-fat diet, an
      HFD, or an HFD supplemented with META060 or rosiglitazone. Body composition was
      determined using dual-energy x-ray absorptiometric analysis. Indirect
      calorimetric measurements were performed to investigate the energy balance in the
      mice, and oral glucose tolerance tests were administered to examine the effect of
      META060 on the glycemic response. RESULTS: The HFD-fed mice administered META060
      for 14 wk had a significantly lower mean weight than HFD-fed mice (30.58 +/- 0.5
      versus 37.88 +/- 0.7 g, P < 0.05). Indirect calorimetric measurements showed an
      increased metabolic flexibility in mice supplemented with META060. In addition,
      glucose tolerance was improved, comparable to the effects of rosiglitazone
      treatment. CONCLUSIONS: META060 has potential therapeutic value for managing
      obesity and insulin resistance, and further research into the mechanism of action
      is warranted.

PMID- 22985973
TI  - Characterization and evaluation of silver release from four different dressings
      used in burns care.
AB  - For centuries silver and silver compounds have been in use to control infection
      and avoid septicaemia in the care of burns and chronic wounds. Renewed interest
      has resulted in a number of Ag based dressings that are now widely used in burns
      centres. Despite extensive use, a systematic study of the chemical composition,
      release kinetics and biochemical action of these products has yet to be
      published. In this work we have characterized the morphology of four commercial
      Ag dressings by scanning electron microscopy and the silver content was
      determined to range between 1.39 mg/cm(2) and 0.03 mg/cm(2). Release kinetics in
      three different matrices (ultra pure water, normal saline solution and a human
      serum substitute) were determined. The highest rates were found in serum
      substitute, with a maximum of 4099 MUg/(hcm(2)) to a minimum of 0.0001
      MUg/(hcm(2)). Our results show that the mean inhibitory concentrations are
      exceeded for most common pathogens in serum substitute and sterile water, but the
      presence of high Cl(-) concentrations tend to inactivate the dressings.

PMID- 22985972
TI  - Pain and symptom management in palliative care and at end of life.
AB  - The purpose of this review is to provide a literature update of the research
      published since 2004 on pain and symptom management in palliative care and at end
      of life. Findings suggest that pain and symptoms are inadequately assessed and
      managed, even at the end of life. Although not pervasive, there is evidence of
      racial/ethnic disparities in symptom management in palliative care and at end of
      life. There is a need for a broader conceptualization and measurement of pain and
      symptom management as multidimensional experiences. There is insufficient
      evidence about mechanisms underlying pain at end of life. Although there are
      advances in the knowledge of pain as a multidimensional experience and the many
      symptoms that occur sometimes with pain, gaps remain. One approach to addressing
      the gaps will involve assessment and management of pain and symptoms as
      multidimensional experiences in people receiving palliative care and at end of
      life.

PMID- 22985975
TI  - Hand function measures for burn patients: a literature review.
AB  - Hand function is one of the most important goals of burn rehabilitation and is a
      consensually important functional outcome. The purpose of this article is to
      review the available hand function measures commonly used for burn patients and
      to summarize their psychometric properties and clinical utilities to serve as
      guidelines for clinical practice and research. An online-database search of
      PubMed, MEDLINE, CINAHL and PsychInfo was performed. One hundred and seventeen
      articles were found and 23 of them met the inclusion and exclusion criteria. The
      eight identified measurement instruments were then classified into three
      categories: traditional component measures, performance measures and patient
      reported outcome measures. Each type of hand function measure has its unique
      characteristics and limitations. Traditional component measures only reflect hand
      impairments, and may not represent hand function status. Performance measures
      have not been validated in the burn population and do not correlate well with
      patient-reported outcomes. Patient-reported outcome measures have not been
      rigorously validated in the burn population. A discussion of how clinicians
      choose these measures reflecting the purposes of their measurements and goals of
      intervention is provided. Moreover, future studies are suggested to develop burn
      specific hand function measures.

PMID- 22985974
TI  - Effects of a hospital based Wellness and Exercise program on quality of life of
      children with severe burns.
AB  - OBJECTIVE: To examine the effect of a 12-week Wellness and Exercise (W&E) program
      on the quality of life of pediatric burn survivors with burns of >=40% total body
      surface area. We hypothesized this comprehensive regimen would improve physical
      and psychosocial outcomes. METHODS: Children were recruited for participation
      upon their discharge from the ICU. They were not taking anabolic/cardiovascular
      agents. Seventeen children participated in the W&E group and 14 children in the
      Standard of Care (SOC) group. Quality of life was assessed with the Child Health
      Questionnaire (CHQ) at discharge and 3 months. Children completed the CHQ-CF 87
      and caregivers completed the CHQ-PF 28. RESULTS: The mean age of children in the
      W&E group was 14.07+/-3.5 years and mean TBSA was 58+/-11.8%. The mean age of
      children in the SOC group was 13.9+/-3.1 years and mean TBSA was 49+/-7.8%. ANOVA
      did not reveal statistically significant differences between the groups. Matched
      paired t-tests revealed that parents with children in the W&E group reported
      significant improvements with their children's physical functioning, role/social
      physical functioning, mental health, overall physical and psychosocial
      functioning after exercise. CONCLUSIONS: These results are clinically relevant in
      that a comprehensive W&E program may be beneficial in promoting physical and
      psychosocial outcomes.

PMID- 22985976
TI  - Burn care facilities are lacking at major trauma centres in England.

PMID- 22985977
TI  - Does calcium disodium EDTA slow CKD progression?

PMID- 22985978
TI  - Oral nutritional supplement use in dialysis patients: full speed ahead?

PMID- 22985979
TI  - Peripherally inserted central catheters and other intravascular devices: how safe
      are they for hemodialysis patients?

PMID- 22985980
TI  - Quiz page October 2012: flank pain, hypertension, and proteinuria.

PMID- 22985981
TI  - Broadband finite-pulse radio-frequency-driven recoupling (fp-RFDR) with (XY8)4(1)
      super-cycling for homo-nuclear correlations in very high magnetic fields at fast
      and ultra-fast MAS frequencies.
AB  - We demonstrate that inter-residue (13)C-(13)C proximities (of about 380 pm) in
      uniformly (13)C-labeled proteins can be probed by applying robust first-order
      recoupling during several milliseconds in single-quantum single-quantum dipolar
      homo-nuclear correlation (SQ-SQ D-HOMCOR) 2D experiments. We show that the
      intensity of medium-range homo-nuclear correlations in these experiments is
      enhanced using broadband first-order finite-pulse radio-frequency-driven
      recoupling (fp-RFDR) NMR sequence with a nested (XY8)4(1) super-cycling. The
      robustness and the efficiency of the fp-RFDR-(XY8)4(1) method is demonstrated at
      high magnetic field (21.1T) and high Magic-Angle Spinning (MAS) speeds (up to 60
      kHz). The introduced super-cycling, formed by combining phase inversion and a
      global four-quantum phase cycle, improves the robustness of fp-RFDR to (i)
      chemical shift anisotropy (CSA), (ii) spread in isotropic chemical shifts, (iii)
      rf-inhomogeneity and (iv) hetero-nuclear dipolar couplings for long recoupling
      times. We show that fp-RFDR-(XY8)4(1) is efficient sans (1)H decoupling, which is
      beneficial for temperature-sensitive biomolecules. The efficiency and the
      robustness of fp-RFDR-(XY8)4(1) is investigated by spin dynamics numerical
      simulations as well as solid-state NMR experiments on [U-(13)C]-L-histidine.HCl,
      a tetra-peptide (Fmoc-[U-(13)C,(15)N]-Val-[U-(13)C,(15)N]-Ala-[U-(13)C,(15)N]-Phe
      Gly-t-Boc) and Al(PO(3))(3).

PMID- 22985982
TI  - Detailed analysis of the TIMES and TIMES0 high-resolution MAS methods for high
      resolution proton NMR.
AB  - We analyze and compare the specifications of TIMES and TIMES(0) proton high
      resolution NMR methods for solid-state samples. This comparison is performed in
      terms of resolution versus magic-angle spinning (MAS) spinning speed, nu(R), rf
      field amplitude, nu(1), and tilt-angle for the effective rf-field, theta(p). The
      chemical-shift and homo-nuclear dipolar scaling factors are calculated for both
      methods. For all MAS speeds, the best resolution is always observed with rf-field
      of nu(1)~120-130 kHz. At slow MAS speed (nu(R)<=10 kHz), the best resolution is
      observed for a tilt-angle of theta(P)~90 degrees . At moderate spinning speed
      (15<=nu(R)<=35 kHz), theta(P)~55 degrees  gives the best resolution. At higher
      MAS speed (nu(R)>=60 kHz), with TIMES and TIMES(0) the best resolution is
      obtained for theta(P)<=40 degrees ; but we then recommend TIMES(0), owing to its
      simpler set-up. We also show that in addition to the usual high rf-field regime
      (nu(1)~120-130 kHz), another low rf-regime (nu(1)~40-50 kHz) exists at MAS speed
      higher than nu(R)>=60 kHz, which also gives a good (1)H resolution. This low rf
      regime should be useful for multi-dimensional analyses of bio-molecules with (1)H
      detection under high-resolution, in order to limit the heating of the sample.

PMID- 22985983
TI  - An international registry for neurodegeneration with brain iron accumulation.
AB  - We report the development of an international registry for Neurodegeneration with
      Brain Iron Accumulation (NBIA), in the context of TIRCON (Treat Iron-Related
      Childhood-Onset Neurodegeneration), an EU-FP7 - funded project. This registry
      aims to combine scattered resources, integrate clinical and scientific knowledge,
      and generate a rich source for future research studies. This paper describes the
      content, architecture and future utility of the registry with the intent to
      capture as many NBIA patients as possible and to offer comprehensive information
      to the international scientific community.

PMID- 22985984
TI  - Parental strain, parental health, and community characteristics among children
      with attention deficit-hyperactivity disorder.
AB  - OBJECTIVE: It has been documented that parenting a child with attention deficit
      hyperactivity disorder (ADHD) can cause family strain, but less is known about
      the added stress of additional child health diagnoses on levels of strain. This
      study explores the relationship between family stressors (such as child comorbid
      conditions) and family resources (such as social support, community
      characteristics, and parental health) on parental strain. METHODS: We used the
      2007 National Survey of Children's Health (NSCH) to identify children with ADHD
      and other comorbid mental and physical health conditions (n = 5473). Descriptive,
      bivariate, and multivariate analyses were conducted to explore the association
      between parental strain, social support, mother's mental health, and neighborhood
      amenities within groups of children with ADHD and comorbid conditions. RESULTS:
      Parental strain was greatest when ADHD was paired with a conduct disorder,
      physical disorder, or other mental health disorder. Specifically, parental strain
      was greatest for children with ADHD plus a comorbid conduct disorder compared
      with ADHD alone. It was also greater for children with other mental and physical
      health diagnoses compared with children with ADHD alone. Better mental health of
      mothers in the sample is related to reduced parental strain. Greater access to
      social support and neighborhood amenities also are related to reduced parental
      strain. CONCLUSIONS: Greater levels of social support and better mental health of
      parents is associated with decreased strain. Interventions aimed at relieving
      stress and building strategies to improve mental health can be beneficial for
      families with children with ADHD and comorbid conditions.

PMID- 22985985
TI  - Dietary and physical activity behaviors of New York City children from different
      ethnic minority subgroups.
AB  - OBJECTIVE: To examine racial/ethnic differences in diet and physical activity
      behaviors in ethnic minority New York City children. METHODS: Cross-sectional
      data from a community-based study of 486 6- to 8-year-old children were used.
      Race/ethnicity was derived using a caregiver's report of child's race and
      Hispanic ancestry. Dietary intake was obtained by 24-hour diet recalls using the
      Nutrition Data System for Research. Physical activity was assessed with
      pedometers and caregiver interviews. We compared diet and activity measures
      across racial/ethnic subgroups using chi-square and analysis of variance tests.
      Multivariate analyses adjusted for age, gender, body mass index, and caregiver
      education (with breastfeeding history and total energy intake included in diet
      models). RESULTS: Participants (N = 486) were categorized as Mexican (29.4%),
      Dominican (8.4%), Puerto Rican (20.6%), other/mixed Hispanic (14.0%), or non
      Hispanic black (27.6%). Obesity rates were lower in non-Hispanic blacks (18%)
      than in Hispanics (31%). Mexicans had the lowest obesity rates among Hispanic
      subgroups (25%), and Dominicans had the highest (39%). There were differences in
      mean daily servings of food groups, with Mexicans having healthier diets and
      Puerto Ricans and non-Hispanic Blacks having less healthy diets. Sedentary time
      was lower in Mexicans than in other groups in adjusted models. Examination of
      additional models, including home language, did not show significant differences
      in the estimates. CONCLUSION: Diet and activity behaviors varied across
      racial/ethnic subgroups. Specifically, Mexican children had healthier diets, the
      least amount of sedentary time, and the lowest rates of obesity among the
      Hispanic subgroups examined. Targeted interventions in ethnic subgroups may be
      warranted to address specific behaviors.

PMID- 22985986
TI  - Effect of cooking at home on the levels of eight phthalates in foods.
AB  - Food products can be contaminated with toxic compounds via the environment.
      Another possibility of food contamination is that toxicants are generated in
      foods or that chemicals migrate from food contact materials into foods during
      processing. In this study, the effect of cooking at home on the levels of
      phthalates - world's most used group of plasticisers - in various food types
      (starchy products, vegetables and meat and fish) was examined. Eight compounds
      were considered, namely dimethyl phthalate (DMP), diethyl phthalate (DEP),
      diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate
      (BBP), di(2-ethylhexyl) phthalate (DEHP), dicyclohexyl phthalate (DCHP) and di-n
      octyl phthalate (DnOP). Food products were analysed before as well as after
      cooking (boiling, steaming, (deep-)frying or grilling). In general, phthalate
      concentrations in foods declined after cooking, except in vegetables, where
      almost no effect was seen. Several factors influenced the degree of this decline
      (e.g. weight difference, fat uptake, etc.). Of all phthalates, DEHP, DiBP and BBP
      were affected the most. In conclusion, cooking at home definitely affected
      phthalate concentrations in foods and thus needs to be considered in order to
      correctly assess humans' dietary exposure to these contaminants.

PMID- 22985987
TI  - Levels of human equilibrative nucleoside transporter-1 are higher in
      proliferating regions of A549 tumor cells grown as tumor xenografts in vivo.
AB  - 3'-Fluoro-3'-deoxythymidine (FLT) has been proposed for positron emission
      tomography (PET)-based identification of tumor chemosensitivity that is mediated
      by the human equilibrative nucleoside transporter-1 (ENT1). ENT1 facilitates
      transport of FLT into cells and elevated levels of FLT are associated with both
      larger FLT-PET signals and increased response to nucleoside-based chemotherapies.
      FLT-PET is also used as a measure of tumor proliferation. The present study
      examined the extent to which ENT1 levels vary in a proliferation-dependent manner
      in tumor cells in vivo. METHODS: The human adenocarcinoma cell line A549 was used
      to establish tumor xenografts in nude mice. FLT uptake was measured in vivo using
      PET, and further examined ex vivo using autoradiography. FLT uptake patterns were
      compared to immunohistochemical (IHC) analysis of ENT1 and the proliferation
      markers Ki67 and BrdU. RESULTS: Regional differences in FLT uptake matched
      differences in IHC proliferation markers. All cells stained for ENT1, but the
      staining intensity was twice as high for Ki67(+) cells than for Ki67(-) cells.
      CONCLUSIONS: Under in vivo conditions, proliferating regions of tumors show
      increased FLT uptake and higher ENT1 levels than nonproliferating tumor regions.

PMID- 22985988
TI  - Structure, histochemistry and ultrastructure of the male reproductive accessory
      glands in the neotropical flat-faced fruit-eating bat Artibeus planirostris
      (Chiroptera: Phyllostomidae).
AB  - Chiroptera, the second largest mammalian order, presents different reproductive
      strategies and unique reproductive features. However, there are few reports
      regarding male reproductive accessory glands (RAGs) in Chiroptera. Thus, the aim
      of the present study was to characterise the RAGs of the exclusively neotropical
      bat Artibeus planirostris (Chiroptera: Phyllostomidae) macroscopically,
      microscopically and ultrastructurally. The RAGs were composed of a prostatic
      complex with two regions (ventral and dorsal) and paraurethral and bulbourethral
      glands, but no seminal vesicles. The ventral region had an undefined epithelium,
      with secretory and basal cells, and its secretions were periodic acid-Schiff
      (PAS) positive. The dorsal region received both deferens ducts, had a columnar
      pseudostratified epithelium with secretory and basal cells. There were two types
      of secretions from the dorsal region: one that was basophilic and another that
      was mixed PAS positive and PAS negative. The paraurethral glands were dispersed
      in the connective tissue of the urethra, whereas the bulbourethral glands were
      located in the penile root. Histological and ultrastructural data confirmed the
      prostatic nature of the ventral and dorsal regions and the holocrine nature of
      the ventral region, with the latter finding never having been described
      previously for the prostate gland. Our findings demonstrate the wide discrepancy
      of RAGs between A. planirostris and other mammals in terms of their composition,
      structure and morphology.

PMID- 22985989
TI  - Endogenous cytokinin profiles and their relationships to between-family
      differences during adventitious caulogenesis in Pinus pinea cotyledons.
AB  - Caulogenesis in mature stone pine (Pinus pinea L.) cotyledons is promoted, to
      varying degrees depending on genotype, by exogenous application of the cytokinin
      (CK) benzyladenine (BA). In the present study, endogenous CK profiles of
      cotyledons from open-pollinated plants and two families of stone pine with widely
      differing organogenic capacities were monitored during caulogenesis and linked to
      previously characterized BA uptake and induction phases. Changes in levels of
      free bases, ribosides, ribotides and glucosides of both isoprenoid and aromatic
      CKs were followed. Before BA application, the pool of endogenous CKs in all sets
      of cotyledons was dominated by isoprenoid ribotides, but 1h after BA exposure,
      aromatic CKs (mainly active free bases and ribosides of topolins) accounted for
      more than 90% of the pool. BA N-glucosides were also observed, levels of which
      (and topolins) rose from 2d until the end of the (six-day) culture period. The CK
      profiles of the two selected pine families also differed, although the general
      trends were similar. During the first 6h, levels of BA and meta-topolin were
      highest in cotyledons from the family with the strongest caulogenic responses,
      while levels of ribotides and aromatic glucosides were highest in cotyledons from
      the other family.

PMID- 22985990
TI  - Molecular cloning, characteristics and low temperature response of raffinose
      synthase gene in Cucumis sativus L.
AB  - Raffinose synthase (RS, EC2.4.1.82) is one of the key enzymes that channels
      sucrose into the raffinose family oligosaccharides (RFOs) biosynthetic pathway.
      However, the gene encoding RS is poorly characterized in cucumber (Cucumis
      sativus L.), which is a typical RFOs-translocating plant species. Here we
      isolated the gene encoding RS (CsRS) from the leaves of cucumber plants. The
      complete cDNA of CsRS consisted of 2552 nucleotides with an open reading frame
      encoding a polypeptide of 784 amino acid residues. Reverse transcription
      polymerase chain reaction and RNA hybridization analysis revealed that expression
      of CsRS was the highest in leaves followed by roots, fruits, and stems. The RS
      activity was up-regulated and the raffinose content was high in the leaves of
      transgenic tobacco with over-expression of CsRS, while both the RS activity and
      the raffinose content decreased in the transgenic cucumber plants with anti-sense
      expression of CsRS. The expression of CsRS could be induced by low temperature
      and exogenous phytohormone abscisic acid (ABA). In cucumber growing under low
      temperature stress, CsRS expression, RS activity and raffinose content increased
      gradually in the leaves, the fruits, the stems and the roots. The most notable
      increase was observed in the leaves. Similarly, the expression of CsRS was
      induced in cucumber leaves and fruits with 200 MUM and 150 MUM ABA treatments,
      respectively.

PMID- 22985991
TI  - Visualizing molecular polar order in tissues via electromechanical coupling.
AB  - Electron microscopy (EM) and atomic force microscopy (AFM) techniques have long
      been used to characterize collagen fibril ordering and alignment in connective
      tissues. These techniques, however, are unable to map collagen fibril polarity,
      i.e., the polar orientation that is directed from the amine to the carboxyl
      termini. Using a voltage modulated AFM-based technique called piezoresponse force
      microscopy (PFM), we show it is possible to visualize both the alignment of
      collagen fibrils within a tissue and the polar orientation of the fibrils with
      minimal sample preparation. We demonstrate the technique on rat tail tendon and
      porcine eye tissues in ambient conditions. In each sample, fibrils are arranged
      into domains whereby neighboring domains exhibit opposite polarizations, which in
      some cases extend to the individual fibrillar level. Uniform polarity has not
      been observed in any of the tissues studied. Evidence of anti-parallel ordering
      of the amine to carboxyl polarity in bundles of fibrils or in individual fibrils
      is found in all tissues, which has relevance for understanding mechanical and
      biofunctional properties and the formation of connective tissues. The technique
      can be applied to any biological material containing piezoelectric biopolymers or
      polysaccharides.

PMID- 22985992
TI  - Occurrence of the Uto-Aztecan premolar trait in a contemporary Colombian
      Amerindian population.
AB  - In 2009, in the Indian Kamentsa community in southern Colombia an oral inspection
      was conducted on 61 young people. Using the methods of Arizona State University's
      Dental Anthropology System (ASUDAS) the presence of unilateral Uto-Aztecan
      premolar (UAP) is reported here.

PMID- 22985993
TI  - Gelatin nanospheres incorporating siRNA for controlled intracellular release.
AB  - The objective of this study is to develop a sustained release system of small
      interfering RNA (siRNA) inside cells aiming at a prolonged time period of gene
      suppression. Gelatin aqueous solution containing luciferase siRNA was coacelvated
      by acetone addition, followed by the glutaraldehyde (GA) crosslinking of gelatin
      to prepare gelatin nanospheres incorporating siRNA. The nanospheres were degraded
      with time in phosphate-buffered saline solution containing collagenase to release
      siRNA incorporated. The nanospheres were degraded more slowly as the GA
      concentration become higher, and consequently the rate of siRNA become lower.
      siRNA was released from the nanospheres as a result of nanospheres degradation.
      The nanospheres were internalized into colon 26 cells luciferase stably
      expressed, irrespective of the GA concentration. The gene expression was
      suppressed by the nanospheres incorporating siRNA capable for the longer-term
      release, and subsequently the time period of gene suppression was prolonged. The
      siRNA release inside the cell was observed, while the release period became
      longer for the slow-degraded nanospheres. It is possible that the intracellular
      siRNA release for a longer time period contributes to the prolonged time period
      of gene suppression.

PMID- 22985994
TI  - Sustained local delivery of bioactive nerve growth factor in the central nervous
      system via tunable diblock copolypeptide hydrogel depots.
AB  - Biomaterial vehicles that can provide sustained, site-specific molecular delivery
      in the central nervous system (CNS) have potential for therapeutic and
      investigative applications. Here, we present in vitro and in vivo proof of
      principle tests of diblock copolypeptide hydrogels (DCH) to serve as depots for
      sustained local release of protein effector molecules. We tested two DCH,
      K(180)L(20) and E(180)L(20), previously shown to self-assemble into
      biocompatible, biodegradable deposits that persist four to eight weeks after
      injection into mouse forebrain. In vitro tests demonstrated sustained release
      from dialysis cassettes of the representative protein, lysozyme, dissolved in
      K(180)L(20) or E(180)L(20) hydrogels. Release time in vitro varied in relation to
      DCH charge and mechanical properties, and ionic strength of the media. To
      evaluate bioactive protein delivery in vivo, we used nerve growth factor (NGF)
      and measured the size of mouse forebrain cholinergic neurons, which respond to
      NGF with cellular hypertrophy. For in vivo tests, the storage modulus of DCH
      depots was tuned to just below that of CNS tissue. In comparison with NGF
      injected in buffer, depots of NGF dissolved in either K(180)L(20) or E(180)L(20)
      provided significantly longer delivery of NGF bioactivity, maintaining
      hypertrophy of local forebrain cholinergic neurons for at least 4 weeks and
      inducing hypertrophy a further distance away (up to 5 mm) from injection sites.
      These findings show that depots of DCH injected into CNS can provide sustained
      delivery within the blood-brain barrier of a bioactive protein growth factor that
      exerts a predicted, quantifiable effect on local cells over a prolonged subacute
      time.

PMID- 22985995
TI  - The calcium-dependent regulation of spheroid formation and cardiomyogenic
      differentiation for MSCs on chitosan membranes.
AB  - Mesenchymal stem cells (MSCs) were recently found to form three-dimensional (3D)
      multicellular spheroids on chitosan membranes. The exact mechanism of spheroid
      formation, however, remains unclear. In this study, the regulation of spheroid
      formation for adipose derived adult stem cells (ADAS) grown on chitosan membranes
      was examined. By varying the membrane thickness, calcium concentration in culture
      medium, and acetylation extent of chitosan, the physico-chemical characteristics
      of chitosan that modulated spheroid formation was elucidated. The capacity of
      cardiomyogenic differentiation was further evaluated. Results suggested that the
      calcium binding capacity of chitosan may affect the cell-substrate and cell-cell
      interactions and critically influence the dynamics of spheroid formation. The
      intracellular calcium level was elevated for ADAS spheroids on chitosan. Chitosan
      bound calcium was observed to enter the cells. The expression of N-cadherin was
      upregulated for ADAS spheroids on chitosan, evidenced by quantitative RT-PCR and
      Western blot. After the induction by 5-aza, the expression levels of cardiac
      marker genes (Gata4, Nkx2.5, Tnnt2, and Myh6) were remarkably enhanced (about
      four-fold) for ADAS on chitosan vs. tissue culture polystyrene or polyvinyl
      alcohol. Immunofluorescence staining confirmed the expression of cardiac
      associated tight junction protein ZO-1 for ADAS grown on chitosan membranes. The
      gene expression of Wnt11 was significantly upregulated for ADAS spheroids on
      chitosan at 3 days and 12 days. We suggested that Wnt11 may be involved in the
      spheroid formation and cardiomyogenic differentiation of MSCs on chitosan
      membranes. Spheroids formed on the acetylated chitosan or polyvinyl alcohol
      membranes failed to show such behavior. The properties of MSC spheroids were
      therefore determined by the culture substrate.

PMID- 22985996
TI  - The differentiation of MSCs into functional hepatocyte-like cells in a liver
      biomatrix scaffold and their transplantation into liver-fibrotic mice.
AB  - Hepatocytes derived from mesenchymal stem cells (MSCs) hold great potential for
      cell-based therapies for liver diseases. The cell-based therapies are critically
      dependent on the hepatic differentiation of the MSCs with a high efficiency and
      on a considerable scale. Recent results have shown that decellularized organs
      provide a three-dimensional extracellular matrix for the lineage restriction of
      stem cell maturation. In this study, we compared the cell proliferation and
      hepatic differentiation of murine MSCs in a biomatrix scaffold from rat liver and
      in the presence and absence growth factors (GF) with a two-dimensional substrate.
      In the absence or presence of GF, the dynamic cultured scaffold (DCS) stimulated
      the MSCs to express endodermal and hepatocyte-specific genes and proteins
      associated with improved functions, and the cells exhibited the ultrastructural
      characteristics of mature hepatocytes. When transplanted into CCl(4)-injured
      mice, the cells pretreated with a combination of the DCS and GF exhibited
      increased survival, liver function, engraftment into the host liver and further
      hepatic differentiation. The paracrine effect of the transplanted cells on
      hepatic stellate cells and native hepatocytes played a key role in the treatment
      of the liver pathology. These studies define an effective method that facilitates
      the hepatic differentiation of MSCs exhibiting extensive functions and support
      further research into the use of a decellularized liver matrix as a bioscaffold
      for liver tissue engineering.

PMID- 22985997
TI  - The role of "anti-inflammatory" cytokines in axon regeneration.
AB  - The injured central and peripheral nervous system (CNS and PNS) are difficult to
      regenerate due to the presence of growth inhibitory molecules which are
      upregulated around the lesion site. In addition, a strong inflammatory response
      triggering the production of so-called "pro"- and "anti-inflammatory" cytokines,
      adds to this dilemma. Both pro- and anti-inflammatory cytokines are involved in
      the regulation of diverse signaling pathways. One of the main aims to induce
      regeneration is to promote axonal outgrowth and stimulate the formation of new
      connections. Anti-inflammatory cytokines as modulators of neurite plasticity and
      outgrowth are of pivotal importance in neuroregeneration with different effects
      reported. Here we summarize the most relevant information about IL-4, IL-10, IL
      13, LIF and TGF-beta focusing on their direct and indirect role in axonal
      outgrowth.

PMID- 22985998
TI  - Family-focused cognitive behaviour therapy versus psycho-education for
      adolescents with chronic fatigue syndrome: long-term follow-up of an RCT.
AB  - The aim of this study was to investigate the long term efficacy of family-focused
      cognitive behaviour therapy (CBT) compared with psycho-education in improving
      school attendance and other secondary outcomes in adolescents with chronic
      fatigue syndrome (CFS). A 24 month follow-up of a randomised controlled trial was
      carried out. Participants received either 13 one-hour sessions of family-focused
      CBT or four one-hour sessions of psycho-education. Forty-four participants took
      part in the follow-up study. The proportion of participants reporting at least
      70% school attendance (the primary outcome) at 24 months was 90% in CBT group and
      84% in psycho-education group; the difference between the groups was not
      statistically significant (OR = 1.29, p = 0.80). The proportion of adolescents
      who had recovered in the family-focused CBT group was 79% compared with 64% in
      the psycho-education, according to a definition including fatigue and school
      attendance. This difference was not statistically significant (Fisher's exact
      test, p = 0.34). Family-focused CBT was associated with significantly better
      emotional and behavioural adjustment at 24 month follow-up compared to psycho
      education, as reported by both adolescents (F = 6.49, p = 0.02) and parents (F =
      4.52, P = 0.04). Impairment significantly decreased in both groups between six
      and 24 month follow-ups, with no significant group difference in improvement over
      this period. Gains previously observed for other secondary outcomes at six month
      follow-up were maintained at 24 month follow-up with no further significant
      improvement or group differences in improvement. In conclusion, gains achieved by
      adolescents with CFS who had undertaken family-focused CBT and psycho-education
      generally continued or were maintained at two-year follow-up. The exception was
      that family-focused CBT was associated with maintained improvements in emotional
      and behavioural difficulties whereas psycho-education was associated with
      deterioration in these outcomes between six and 24-month follow-up.

PMID- 22985999
TI  - Advance of advantageous genes for a multiple-allele population genetics model.
AB  - This paper extends the classical result of Fisher (1937) from the case of two
      alleles to the case of multiple alleles. Consider a population living in a
      homogeneous one-dimensional infinite habitat. Individuals in this population
      carry a gene that occurs in k forms, called alleles. Under the joint action of
      migration and selection and some additional conditions, the frequencies of the
      alleles, p(i),i=1,...,k, satisfy a system of differential equations of the form
      (1.2). In this paper, we first show that under the conditions A(1)A(1) is the
      most fit among the homozygotes, (1.2) is cooperative, the state that only allele
      A(1) is present in the population is stable, and the state that allele A(1) is
      absent and all other alleles are present in the population is unstable, then
      there exists a positive constant, c(*), such that allele A(1) propagates
      asymptotically with speed c(*) in the population as t->infinity. We then show
      that traveling wave solutions connecting these two states exist for |c|>=c(*).
      Finally, we show that under certain additional conditions, there exists an
      explicit formula for c(*). These results allow us to estimate how fast an
      advantageous gene propagates in a population under selection and migration forces
      as t->infinity. Selection is one of the major evolutionary forces and
      understanding how it works will help predict the genetic makeup of a population
      in the long run.

PMID- 22986000
TI  - c-Ski inhibits the proliferation of vascular smooth muscle cells via suppressing
      Smad3 signaling but stimulating p38 pathway.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) plays key roles in the
      progression of intimal hyperplasia, but the molecular mechanisms that trigger
      VSMC proliferation after vascular injury remain unclear. c-Ski, a co-repressor of
      transforming growth factor beta (TGF-beta)/Smad signaling, was detected to
      express in VSMC of rat artery. During the course of arterial VSMC proliferation
      induced by balloon injury in rat, the endogenous protein expressions of c-Ski
      decreased markedly in a time-dependent manner. In vivo c-Ski gene delivery was
      found to significantly suppress balloon injury-induced VSMC proliferation and
      neointima formation. Further investigation in A10 rat aortic smooth muscle cells
      demonstrated that overexpression of c-Ski gene inhibited TGF-beta1 (1 ng/ml)
      induced A10 cell proliferation while knockdown of c-Ski by RNAi enhanced the
      stimulatory effect of TGF-beta1 on A10 cell growth. Western blot for signaling
      detection showed that suppression of Smad3 phosphorylation while stimulating p38
      signaling associated with upregulation of cyclin-dependent kinase inhibitors p21
      and p27 was responsible for the inhibitory effect of c-Ski on TGF-beta1-induced
      VSMC proliferation. These data suggest that the decrease of endogenous c-Ski
      expression is implicated in the progression of VSMC proliferation after arterial
      injury and c-Ski administration represents a promising role for treating intimal
      hyperplasia via inhibiting the proliferation of VSMC.

PMID- 22986001
TI  - Intermittent photic stimulation affects motor cortex excitability in
      photosensitive idiopathic generalized epilepsy.
AB  - PURPOSE: To assess the effect of intermittent photic stimulation (IPS) at a
      common activating frequency, i.e. 20Hz, on motor cortex excitability by means of
      transcranial magnetic stimulation (TMS) in photosensitive patients with
      idiopathic generalized epilepsy (IGE). METHODS: We studied 15 photosensitive IGE
      patients showing a photoparoxysmal response (PPR) to IPS at 20Hz. Nineteen normal
      subjects of similar age and sex acted as controls. After the resting motor
      threshold (rMT) was measured, we studied the corticomotor excitability in two
      conditions randomly delivered, during IPS (5s) at 20Hz and without IPS. Motor
      evoked potentials (MEPs) were recorded from the right first dorsal interosseous
      muscle (FDI). We determined the cortical silent period (cSP), the short-latency
      intracortical inhibition (SICI) at the interstimulus interval (ISI) of 3 and 4ms
      and the intracortical facilitation (ICF) at ISIs of 12 and 14ms. Data were
      analyzed by means of rmANOVAs. RESULTS: IPS at 20Hz is significantly shortening
      the cSP in normal subjects, while no significant changes were detected in
      patients. The rMT was significantly higher in patients than controls, as expected
      by the concurrent antiepileptic treatment. Other corticomotor excitability
      measures were unaffected. CONCLUSIONS: We confirm that IPS has a weak influence
      on the motor cortical output in patients with IGE and PPR. The loss of the normal
      shortening of the cSP, otherwise present in healthy subjects in response to IPS,
      may have a possible protective nature.

PMID- 22986002
TI  - Assessing functional diversity in the soybean beta-substituted alanine synthase
      enzyme family.
AB  - In plants, proteins of the beta-substituted alanine synthase (BSAS) enzyme family
      perform a diverse range of reactions, including formation of cysteine from O
      acetylserine and sulfide, detoxification of cyanide by its addition to cysteine,
      the breakdown of cysteine into pyruvate, ammonia, and sulfide, and the synthesis
      of S-sulfocysteine. With the completed genome sequence of soybean (Glycine max
      (L.) Merr. cv. Williams 82), the functional diversity of the BSAS in this highly
      duplicated plant species was examined to determine whether soybean BSAS enzymes
      catalyze the various reactions connected to cysteine metabolism. The 16 soybean
      BSAS can be grouped into clades that are similar to those observed in
      Arabidopsis. Biochemical analysis of soybean BSAS proteins demonstrate that
      enzymes of clades I and III function as O-acetylserine sulfhydrylases for
      cysteine synthesis, clade II encodes cysteine desulfhydrase activity, and that
      clade V proteins function as beta-cyanoalanine synthase for cyanide
      detoxification. Although clade IV is similar to Arabidopsis S-sulfocysteine
      synthase, this activity was not detected in the soybean homolog. Overall, our
      results show that bioinformatics approach provides a useful method to assess the
      biochemical properties of BSAS enzymes in plant species.

PMID- 22986003
TI  - Analysis of immunogenicity of different protein groups from malaria parasite
      Plasmodium falciparum.
AB  - It was observed that pressure of host immune system leads to diversifying
      selection (which can be measured in terms of pN/pS ratio). In this research we
      checked whether Plasmodium falciparum proteins containing experimentally evident
      epitopes from the IEDB database are subject to diversifying selection. We also
      investigated which life stage of this parasite and which proteins are subject to
      the strongest immune pressure. To answer these questions we used information
      about experimentally evident epitopes from P. falciparum, that interact with
      human immune system and sequences of different isolates of P. falciparum obtained
      from PlasmoDB. We confirmed the expectations that proteins containing IEDB
      epitopes are subject to stronger diversifying selection which is evidenced by
      higher pN/pS ratio. A stage characterized by the highest average pN/pS ratio is
      that of the sporozoite. The greatest fraction of putative antigens is also
      present at this stage. We also found that the sporozoite stage is particularly
      interesting for further analysis as it potentially contains the highest number of
      unidentified epitopes.

PMID- 22986004
TI  - Extending David Horrobin's membrane phospholipid theory of schizophrenia:
      overactivity of cytosolic phospholipase A(2) in the brain is caused by overdrive
      of coupled serotonergic 5HT(2A/2C) receptors in response to stress.
AB  - David Horrobin's membrane phospholipid theory of schizophrenia has held up well
      over time because his therapeutic prediction that dietary supplementation with
      eicosapentaenoic acid (EPA) would have a therapeutic effect has been partially
      verified and undergoes continued testing. In the final version of his theory, he
      hypothesized that there was hyperactivity of phosphoslipase A(2) (PLA(2)) or a
      related enzyme but did not explain how the hyperactivity came about. It is known
      that serotonergic 5HT(2A/2C) receptors are coupled to PLA(2), which hydrolyzes
      both arachidonic acid (AA) and EPA from diacylglycerides at the sn-2 position. In
      this paper, Horrobin's theory is combined with a previously published theory of
      chronic stress in which it was hypothesized that a disinhibited dorsal raphe
      nucleus, the principal nucleus of the serotonergic system, can organize the
      neuropathology of diseases such as migraine, hypertension, and the metabolic
      syndrome. The new or combined theory is that schizophrenia is a disease of
      chronic stress in which a disinhibited DRN causes widespread serotonergic
      overdrive in the cerebral cortex. This in turn causes overdrive of cPLA(2) and
      both central and peripheral depletion of AA and EPA. Because EPA is present in
      smaller amounts, it falls below threshold for maintaining an intracellular
      balance between AA-derived and EPA-derived second messenger cascades, which leads
      to abnormal patterns of neuronal firing. There are two causes of neuronal
      dysfunction: the disinhibited DRN and EPA depletion. Schizophrenia is
      statistically associated with metabolic syndrome, hypertension, and migraine
      because they form a cluster of diseases with similar pathophysiology. The theory
      provides an explanation for both the central and peripheral phospholipid
      abnormalities in schizophrenia. It also explains the role of stress in
      schizophrenia, elevated serum PLA(2) activity in schizophrenia, the relationship
      between untreated schizophrenia and metabolic syndrome, and the therapeutic
      rationale for EPA.

PMID- 22986005
TI  - Manipulation of the extrastriate frontal loop can resolve visual disability in
      blindsight patients.
AB  - Patients with blindsight are not consciously aware of visual stimuli in the
      affected field of vision but retain nonconscious perception. This disability can
      be resolved if nonconsciously perceived information can be brought to their
      conscious awareness. It can be accomplished by manipulating neural network of
      visual awareness. To understand this network, we studied the pattern of cortical
      activity elicited during processing of visual stimuli with or without conscious
      awareness. The analysis indicated that a re-entrant signaling loop between the
      area V3A (located in the extrastriate cortex) and the frontal cortex is critical
      for processing conscious awareness. The loop is activated by visual signals
      relayed in the primary visual cortex, which is damaged in blindsight patients.
      Because of the damage, V3A-frontal loop is not activated and the signals are not
      processed for conscious awareness. These patients however continue to receive
      visual signals through the lateral geniculate nucleus. Since these signals do not
      activate the V3A-frontal loop, the stimuli are not consciously perceived. If
      visual input from the lateral geniculate nucleus is appropriately manipulated and
      made to activate the V3A-frontal loop, blindsight patients can regain conscious
      vision.

PMID- 22986006
TI  - Hypothesis: Chlamydia trachomatis infection of the female genital tract is
      controlled by Type 2 immunity.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium sexually transmitted
      to more than 90 million individuals each year. As this level of infectivity
      implies, C. trachomatis is a successful human parasite; a success facilitated by
      its ability to cause asymptomatic infection. Host defense against C. trachomatis
      in the female genital tract is not well defined, but current dogma suggests
      infection is controlled largely by T(H)1 immunity. Conversely, it is well
      established that T(H)2 immunity controls allergens, helminths, and other
      extracellular pathogens that cause repetitive or persistent T cell stimulation
      but do not induce the exuberant inflammation that drives T(H)1 and T(H)17
      immunity. As C. trachomatis persists in female genital tract epithelial cells but
      does not elicit over tissue inflammation, we now posit that defense is maintained
      by Type 2 immune responses that control bacterial growth but minimize
      immunopathological damage to vital reproductive tract anatomy. Evaluation of this
      hypothesis may uncover novel mechanisms by which Type 2 immunity can control
      growth of C. trachomatis and other intracellular pathogens, while confirmation
      that T(H)2 immunity was selected by evolution to control C. trachomatis infection
      in the female genital tract will transform current research, now focused on
      developing vaccines that elicit strong, and therefore potentially tissue
      destructive, Chlamydia-specific T(H)1 immunity.

PMID- 22986007
TI  - Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive
      spinocerebellar ataxia.
AB  - BACKGROUND: Congenital nonprogressive spinocerebellar ataxia is characterized by
      early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria.
      The clinical presentation remains fairly stable and may be associated with
      cerebellar atrophy. To date, only a few families with autosomal dominant
      congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to
      3pter was demonstrated in one large Australian family and this locus was
      designated spinocerebellar ataxia type 29. The objective of this study is to
      describe an unreported Canadian family with autosomal dominant congenital
      nonprogressive spinocerebellar ataxia and to identify the underlying genetic
      causes in this family and the original Australian family. METHODS AND RESULTS:
      Exome sequencing was performed for the Australian family, resulting in the
      identification of a heterozygous mutation in the ITPR1 gene. For the Canadian
      family, genotyping with microsatellite markers and Sanger sequencing of ITPR1
      gene were performed; a heterozygous missense mutation in ITPR1 was identified.
      CONCLUSIONS: ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a
      ligand-gated ion channel that mediates calcium release from the endoplasmic
      reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15,
      a distinct and very slowly progressive form of cerebellar ataxia with onset in
      adulthood. Our study demonstrates for the first time that, in addition to
      spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct
      congenital nonprogressive ataxia; highlighting important clinical heterogeneity
      associated with the ITPR1 gene and a significant role of the ITPR1-related
      pathway in the development and maintenance of the normal functions of the
      cerebellum.

PMID- 22986008
TI  - Health and social fields in the context of lifestyle migration.
AB  - Migrants occupy different social fields encompassing both their origin and their
      destination. Much previous work on interactions within these fields has focused
      on economic migrants. In this paper we seek to understand the social fields
      occupied by British pensioners who have moved to Spain and how these interact
      with their health and their experience of the healthcare system. We explore the
      links between health, social fields, healthcare, place and social relationships.
      We use in-depth interviews conducted among those living in a variety of settings.
      We draw upon Bourdieu's concept of habitus and social fields and differentiate,
      between ways of being and ways of belonging in the fields. We identified three
      social fields. The first embraced interviewees' social networks back in the UK
      where implicit comparisons of healthcare were made. The second embraced their
      expatriate social networks in Spain which includes their conceptualization of a
      "healthy life", while the third included the interaction with Spanish
      institutions, including the healthcare system. This conceptual framework provides
      new insights for those considering retirement abroad, and those that want to
      understand how lifestyles and navigating distinct social fields influence health
      and the healthcare experience.

PMID- 22986009
TI  - Contact lens dropouts--'must try harder'.

PMID- 22986010
TI  - Prognostic factors during outpatient treatment for alcohol dependence: cohort
      study with 6 months of treatment follow-up.
AB  - AIMS: To identify prognostic factors to outpatient alcohol treatment on admission
      as well as during the treatment period. METHODS: A cohort study of n = 209
      alcoholic patients (DSM-IV) during 6 months of outpatient treatment. Eight
      medical doctors from two hospitals were involved. Co-responsible participation in
      treatment was a necessary condition. At admission, we documented socio
      demographic factors, use of other drugs and severity of alcohol consumption.
      During the 6 months, we observed medication for prevention of alcohol relapse
      [disulfiram (DIS), acamprosate], number of sessions with the doctor, number of
      phases of the consultation and medication for depression. Primary outcome
      variables were time to first heavy relapse and abstinence of heavy alcohol
      consumption. These were measured with Timeline Followback. Five or more alcohol
      units of 10 g in one relapse day were considered heavy relapse. RESULTS: The
      patients were 84% males, with 41 years median age; the median alcohol consumption
      was 192 g per day with a median duration of 13 years of heavy consumption. The
      median education was 6 years with 61% of the patients from lower socio-economic
      levels. The Kaplan-Meier heavy relapse rate at 6 months was 23%. On admission to
      treatment, female gender, lower socio-economic levels, cocaine use, >20 years of
      consumption, gamma glutamyl transferase values above normal and five or more
      alcohol-related problems on the Alcohol-Related Problem Questionnaire predicted
      worse outcomes. Having a full-time job and shorter abstinence time before
      treatment (until 7 days) predicted better outcomes. During the 6 months, we found
      that DIS for <120 days was a prognostic factor of worse outcomes. DIS for at
      least 120 days, >50% of adherence to consultations and more than two phases on
      each consultation predicted better outcomes. The combined sensitivity and
      specificity for DIS for at least 120 days, >50% of adherence to consultations and
      more than two phases on consultation regarding abstinence from heavy relapse were
      respectively 100 and 71%. CONCLUSIONS: During 6 months of outpatient treatment,
      longer adherence to DIS and consultations as well as more phases in a
      consultation involving necessarily a co-responsible predict a good outcome
      independently of the patient features at admission.

PMID- 22986011
TI  - Is there a relationship between alcohol quality and health?
AB  - A clear definition of 'alcohol quality' is currently not available and the use of
      the term varies considerably depending on the scientific field and the individual
      author. Intrinsic factors of 'alcohol quality' may be taste and flavour or the
      absence of certain toxic contaminants. Extrinsic factors may include price, brand
      image, labelling or perceived authenticity, which are typically unrelated to
      public health outcomes. This article shows that using the term 'alcohol quality'
      with varying definitions and underlying concepts may lead to misunderstandings,
      if not to clear misinformation (sometimes also intentionally by industry) when
      'lower quality' is interpreted as 'more toxic' especially in the case of
      substitution of commercial beverages to unrecorded alcohol. We suggest the use of
      clearly defined terms instead, such as 'taste quality' or 'brand price', whenever
      possible.

PMID- 22986012
TI  - The cytokines cardiotrophin-like cytokine/cytokine-like factor-1 (CLC/CLF) and
      ciliary neurotrophic factor (CNTF) differ in their receptor specificities.
AB  - Ciliary neurotrophic factor (CNTF) and cardiotrophin-like cytokine (CLC) are two
      cytokines with neurotrophic and immunomodulatory activities. CNTF is a
      cytoplasmic factor believed to be released upon cellular damage, while CLC
      requires interaction with a soluble cytokine receptor, cytokine-like factor 1
      (CLF), to be efficiently secreted. Both cytokines activate a receptor complex
      comprising the cytokine binding CNTF receptor alpha (CNTFRalpha) and two
      signaling chains namely, leukemia inhibitory factor receptor beta (LIFRbeta) and
      gp130. Human CNTF can recruit and activate an alternative receptor in which
      CNTFRalpha is substituted by IL-6Ralpha. As both CNTF and CLC have immune
      regulatory activities in mice, we compared their ability to recruit mouse
      receptors comprising both gp130 and LIFRbeta signaling chains and either IL
      6Ralpha or IL-11Ralpha which, unlike CNTFRalpha, are expressed by immune cells.
      Our results indicate that 1) mouse CNTF, like its human homologue, can activate
      cells expressing gp130/LIFRbeta with either CNTFRalpha or IL-6Ralpha and, 2)
      CLC/CLF is more restricted in its specificity in that it activates only the
      tripartite CNTFR. Several gp130 signaling cytokines influence T helper cell
      differentiation. We therefore investigated the effect of CNTF on CD4 T cell
      cytokine production. We observed that CNTF increased the number of IFN-gamma
      producing CD4 T cells. As IFN-gamma is considered a mediator of the therapeutic
      effect of IFN-beta in multiple sclerosis, induction of IFN-gamma by CNTF may
      contribute to the beneficial immunomodulatory effect of CNTF in mouse multiple
      sclerosis models. Together, our results indicate that CNTF activates the same
      tripartite receptors in mouse and human cells and further validate rodent models
      for pre-clinical investigation of CNTF and CNTF derivatives. Furthermore, CNTF
      and CLC/CLF differ in their receptor specificities. The receptor alpha chain
      involved in the immunomodulatory effects of CLC/CLF remains to be identified.

PMID- 22986013
TI  - A whole blood in vitro cytokine release assay with aqueous monoclonal antibody
      presentation for the prediction of therapeutic protein induced cytokine release
      syndrome in humans.
AB  - The administration of several monoclonal antibodies (mAbs) to humans has been
      associated with acute adverse events characterized by clinically significant
      release of cytokines in the blood. The limited predictive value of toxicology
      species in this field has triggered intensive research to establish human in
      vitro assays using peripheral blood mononuclear cells or blood to predict
      cytokine release in humans. A thorough characterization of these assays is
      required to understand their predictive value for hazard identification and risk
      assessment in an optimal manner, and to highlight potential limitations of
      individual assay formats. We have characterized a whole human blood cytokine
      release assay with only minimal dilution by the test antibodies (95% v/v blood)
      in aqueous presentation format, an assay which has so far received less attention
      in the scientific world with respect to the evaluation of its suitability to
      predict cytokine release in humans. This format was compared with a human PBMC
      assay with immobilized mAbs presentation already well-characterized by others.
      Cytokine secretion into plasma or cell culture supernatants after 24h incubation
      with the test mAbs (anti-CD28 superagonist TGN1412-like material (TGN1412L),
      another anti-CD28 superagonistic mAb (ANC28.1), a T-cell depleting mAb
      (OrthocloneTM), and a TGN1412 isotype-matched control (TysabriTM) not associated
      with clinically-relevant cytokine release) was detected by a multiplex assay
      based on electrochemiluminescent excitation. We provide proof that this whole
      blood assay is a suitable new method for hazard identification of safety-relevant
      cytokine release in the clinic based on its ability to detect the typical
      cytokine signatures found in humans for the tested mAbs and on a markedly lower
      assay background and cytokine release with the isotype-matched control mAb
      TysabriTM - a clear advantage over the PBMC assay. Importantly, quantitative and
      qualitative differences in the relative cytokine responses to the individual
      mAbs, in the concentration-response relationships and the prominent cytokine
      signatures for individual mAbs in the two formats reflect diverging mechanisms of
      cytokine release and different levels of dependency on high density coating even
      for two anti-CD28 super-agonistic antibodies. These results clearly show that one
      generic approach to assessment of cytokine release using in vitro assays is not
      sufficient, but rather the choice of the method, i.e. applying the whole blood
      assay or the PBMC assay needs to be well considered depending on the target
      characteristics and the mechanistic features of the therapeutic mAbs being
      evaluated.

PMID- 22986014
TI  - Impact of a surgical site infection (SSI) surveillance program in orthopedics and
      traumatology.
AB  - Surveillance of surgical site infections (SSI) is a priority. One of the
      fundamental principles for the surveillance of SSI is based on receiving
      effective field feedback (retro-information). The aim of this study was to report
      the results of a program of SSI surveillance and validate the hypothesis that
      there is a correlation between creating a SSI surveillance program and a
      reduction in SSI. MATERIALS AND METHODS: The protocol was based on the weekly
      collection of surveillance data obtained directly from the different information
      systems in different departments. A delay of 3 months was established before
      extraction and analysis of data and information from the surgical teams. The NNIS
      index (National Nosocomial Infections Surveillance System) developed by the
      American surveillance system and the reduction of length of hospital stay index
      Journees d'hospitalisation evitees (JHE). RESULTS: Since the end of 2009, 7156
      surgical procedures were evaluated (rate of inclusion 97.3%), and 84 SSI were
      registered with a significant decrease over time from 1.86% to 0.66%. A total of
      418 days of hospitalization have been saved since the beginning of the
      surveillance system. DISCUSSION: Our surveillance system has three strong points:
      follow-up is continuous, specifically adapted to orthopedic traumatology and
      nearly exhaustive. The extraction of data directly from hospital information
      systems effectively improves the collection of data on surgical procedures. The
      implementation of a SSI surveillance protocol reduces SSI. LEVEL OF EVIDENCE:
      Level III. Prospective study.

PMID- 22986015
TI  - Early surgical site infection in adult appendicular skeleton trauma surgery: a
      multicenter prospective series.
AB  - INTRODUCTION: Surgical site infections (SSI) studies rely on an imprecise and
      debatable definition. The term "wound healing problems" (WHP), not necessarily
      septic, is also frequently cited. This study had the objectives of determining
      the frequency of early SSIs in traumatology, these terms eventual correlation,
      and the factors influencing onset. PATIENTS AND METHODS: A multicenter
      prospective observational study was conducted in 12 centers. The exclusion
      criteria were open lesions as well as multiple injuries and multiple fractures
      (more than two fractures treated surgically). All patients were followed for the
      first three postoperative months until there was clinical certainty of healing
      and absence of infection. The presence of any WHP or SSI required a minimum
      follow-up of 1 year. WHP and SSI risk factors were determined using logistical
      regression adjusted on the centers. RESULTS: Out of 1617 cases, 103 were
      complicated by a WHP and 22 by a SSI. The SSIs were mainly secondary to
      Staphylococcus infections. The factors predisposing the patients to WHP and SSI
      (p<=0.05) were age; the NNIS, ASA, and Parker scores; alcoholism; antiaggregant
      use; and the locoregional aspect at the time of injury. The 522 subcutaneous
      osteosyntheses "near the skin" resulted in 58 WHPs (11%) and 14 SSIs (2.7%); 13
      of the 58 WHPs (22%) resulted in one SSI. Out of 707 deep osteosyntheses, 24
      (3.4%) presented a WHP and seven (1%) a SSI; Four SSIs originated from a WHP. The
      352 fractures of the trochanter were complicated by a WHP in 15 cases (5.5%) and
      a SSI in one case (0.4%) after interlocked nailing and two WHPs and two SSIs
      (2.5%) after screw and plate fixation. Of the 388 first-line arthroplasties, only
      the prostheses implanted for a proximal femur fracture presented complications:
      21 WHPs (6%) and one SSI (0.02%). Of the 103 WHPs of the entire series, 18 became
      SSIs. In absence of WHP, the SSI rate was 0.2%, whereas the probability of a WHP
      evolving toward a SSI was 100 times higher. The only factor significantly
      associated with a WHP becoming a SSI was osteosynthesis material exposure.
      DISCUSSION: This prospective study can be criticized on several points: the
      deliberately limited inclusion criteria, the short follow-up, and the possible
      subjectivity of the data collection. The SSI rates reported are for the most part
      in agreement with the literature. This study is innovative in traumatology given
      the large number of patients and the notion of WHP that was preferred over
      superficial infection. It demonstrates the relations between WHP and SSI, in
      particular for osteosyntheses near the skin. LEVEL OF EVIDENCE: Level III.

PMID- 22986016
TI  - Molecular genetics in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are diagnosed by a combination of cytomorphology
      and cytogenetics. Fluorescence in situ hybridisation (FISH) can accompany
      cytogenetic results or can in some cases also be performed instead of chromosome
      banding analysis. In recent years also immunophenotyping added important
      information for the diagnosis of MDS. So far, diagnosis however still depends on
      cytomorphology of peripheral blood and bone marrow smears. The prognostication is
      done according to the IPSS or very recently to the revised IPSS by a combination
      of cytopenia, morphologic features according to the WHO classification (2008) and
      cytogenetic results. In addition, also molecular markers have been shown to
      contribute important information for diagnosis and also for prognosis in patients
      with MDS. These markers are in some cases found by next generation sequencing
      including whole exome sequencing of patients with MDS. Prospective analysis will
      show the best combination of methods to diagnose patients with MDS or to define
      their respective prognosis. Without doubt, mutations in newly depicted genes,
      including genes involved in the spliceosome, will be included in the management
      of MDS patients.

PMID- 22986017
TI  - Uncovering the connection between artist and audience: viewing painted
      brushstrokes evokes corresponding action representations in the observer.
AB  - Observed actions are covertly and involuntarily simulated within the observer's
      motor system. It has been argued that simulation is involved in processing
      abstract, gestural paintings, as the artist's movements can be simulated by
      observing static brushstrokes. Though this argument is grounded in theory,
      empirical research has yet to examine the claim. Five experiments are described
      wherein participants executed arm movements resembling the act of painting
      horizontal brushstrokes while observing paintings featuring broad, discernable
      brushstrokes. Participants responded faster when their movement was compatible
      with the observed brushstrokes, even though the paintings were irrelevant to
      their task. Additional results suggest that this effect occurs outside of
      awareness. These results provide evidence that observers can simulate the actions
      of the painter by simply observing the painting, revealing a connection between
      artist and audience hitherto undemonstrated by cognitive science.

PMID- 22986018
TI  - The development of abstract syntax: evidence from structural priming and the
      lexical boost.
AB  - Structural priming paradigms have been influential in shaping theories of adult
      sentence processing and theories of syntactic development. However, until
      recently there have been few attempts to provide an integrated account that
      explains both adult and developmental data. The aim of the present paper was to
      begin the process of integration by taking a developmental approach to structural
      priming. Using a dialog comprehension-to-production paradigm, we primed
      participants (3-4year olds, 5-6year olds and adults) with double object datives
      (Wendy gave Bob a dog) and prepositional datives (Wendy gave a dog to Bob). Half
      the participants heard the same verb in prime and target (e.g. gave-gave) and
      half heard a different verb (e.g. sent-gave). The results revealed substantial
      differences in the magnitude of priming across development. First, there was a
      small but significant abstract structural priming effect across all age groups,
      but this effect was larger in younger children than in older children and adults.
      Second, adding verb overlap between prime and target prompted a large,
      significant increase in the priming effect in adults (a lexical boost), a small,
      marginally significant increase in the older children and no increase in the
      youngest children. The results support the idea that abstract syntactic knowledge
      can develop independently of verb-specific frames. They also support the idea
      that different mechanisms may be needed to explain abstract structural priming
      and lexical priming, as predicted by the implicit learning account (Bock, K., &
      Griffin, Z. M. (2000). The persistence of structural priming: Transient
      activation or implicit learning? Journal of Experimental Psychology - General,
      129(2), 177-192). Finally, the results illustrate the value of an integrative
      developmental approach to both theories of adult sentence processing and theories
      of syntax acquisition.

PMID- 22986019
TI  - The impact of confounders on the test performance of natriuretic peptides for
      cardiac dysfunction in subjects aged 80 and older.
AB  - The hypothesis that natriuretic peptides could be used to identify 'pancardiac'
      damage has been proposed. However, multiple factors are known to influence
      circulating levels of natriuretic peptides, especially in the very old.
      Therefore, the impact of confounders on the association between natriuretic
      peptide levels and cardiac dysfunction was further explored in subjects aged 80
      and older. A diagnostic cross-sectional study embedded within the BELFRAIL study
      (n=567) was performed. Baseline BNP and NT-proBNP levels were measured and
      echocardiograms were performed at the subject's home. Cardiac dysfunction was
      defined as systolic dysfunction, valvular heart disease or isolated severe
      diastolic dysfunction. Several functional and structural echocardiographic
      parameters were independently related to circulating levels of natriuretic
      peptides. Cystatin C, BMI, beta blockers, diabetes, heart frequency, usCRP, age
      and sex were identified as confounders. The prevalence of cardiac dysfunction was
      17.1% in the subjects without and 30.8% in the subjects with chronic atrial
      fibrillation (CAF) or pacemaker (PM). Only in subjects with CAF or PM the C
      statistic for cardiac dysfunction improved after correcting for confounders. The
      post-test probability for a negative test (PTP-) ranged from 3.7% to 12.2% and
      the PTP+ ranged from 21.9% to 62.2% in different strata of confounders. According
      to these data adjusting for identified confounders does not improve the
      diagnostic accuracy of the natriuretic peptides for cardiac dysfunction, except
      in subjects with CAF or PM. Stratifying for individual confounders showed that
      different cut-off values could be used to optimize the diagnostic characteristics
      of natriuretic peptides.

PMID- 22986020
TI  - Cardiovascular effects of a PEGylated apelin.
AB  - Several studies have documented cardiovascular effects of apelin, including
      enhanced inotropy and vasodilation. However, these cardiovascular effects are
      short lived due to the predicted short circulating half-life of the apelin
      peptide. To address this limitation of apelin, we pursued N-terminal PEGylation
      of apelin and examined the cardiovascular effects of the PEGylated apelin. A
      40kDa PEG conjugated apelin-36 (PEG-apelin-36) was successfully produced with N
      terminal conjugation, high purity (>98%) and minimum reduction of APJ receptor
      binding affinity. Using an adenylate cyclase inhibition assay, comparable in
      vitro bioactivity was observed between the PEG-apelin-36 and unmodified apelin
      36. In vivo evaluation of the PEG-apelin-36 was performed in normal rats and rats
      with myocardial infarction (MI). Cardiac function was assessed via
      echocardiography before, during a 20 min IV infusion and up to 100 min post
      peptide infusion. Similar increases in cardiac ejection fraction (EF) were
      observed during the infusion of PEG-apelin-36 and apelin-36 in normal rats.
      However, animals that received PEG-apelin-36 maintained significantly increased
      EF over the 100 min post infusion monitoring period compared to the animals that
      received unmodified apelin-36. Interestingly, EF increases observed with PEG
      apelin-36 and apelin-36 were greater in the MI rats. PEG-apelin-36 had a
      prolonged circulating life compared to apelin-36 in rats. There were no changes
      in aortic blood pressure when PEG-apelin-36 or apelin-36 was administered. To our
      knowledge this is the first report of apelin PEGylation and documentation of its
      cardiovascular effects.

PMID- 22986021
TI  - GLP-1 expression in von Ebner's gland of diabetic rats.
AB  - GLP-1, a peptidergic endocrine hormone, which associate with appetite control,
      glucose homeostasis and satiety. It might play an important role in the gustatory
      system. We tried to investigate the expression of GLP-1 in von Ebner's gland of
      diabetic and control rats, and the ultrastructure changes on von Ebner's gland of
      diabetes rats. GLP-1 expression in von Ebner's gland was evaluated by
      immunohistochemistry. The number of GLP-1 positive cells in diabetic rat von
      Ebner's gland was significantly higher than that in normal controls. Electron
      micrographs showed that a series of pathologic changes in von Ebner's gland of
      diabetes rats. The results suggest that GLP-1 have some effects within the
      gustatory systems, and elevated von Ebner's gland GLP-1 expression may be one
      cause of diabetic taste impairment.

PMID- 22986022
TI  - Shotgun cholanomics of ileal fluid.
AB  - In this study we have developed a rapid method for the shotgun analysis of bile
      acids in intestinal fluid. The method is semi-quantitative, and requires little
      sample preparation. Bile salts might contribute to the pathogenesis of Crohn's
      disease. In a pilot study we demonstrate the method by analysing the bile acid
      content of ileal fluid from seven Crohn's disease patients and three healthy
      controls. The dominant bile acids observed were di and/or trihydroxycholanoates,
      di- and/or trihydroxycholanoylglycines, di- and/or tri-hydroxycholanoyltaurines,
      monosulphated dihydroxycholanoates and monosulphated dihydroxycholanoylglycine.
      The method can be similarly applied to samples derived from other parts of the
      intestine.

PMID- 22986023
TI  - Epigenetic regulation of oxysterol formation.
AB  - Oxysterols are oxygenated derivatives of cholesterol that may be formed by either
      enzymatic or non-enzymatic mechanisms. Expression of the genes responsible for
      oxysterol synthesis (GROS) is known to be restricted across different tissues and
      cell types. Regulation of the transcription of GROS and the activity of their
      enzyme transcripts has been the subject of intense activity for many years.
      Recent studies have sought to decipher the mechanism(s) that underpin the
      restricted expression of the GROS. Available data indicates that epigenetic
      mechanisms have an important role to play in the control of the expression of
      GROS. In the current review we summarize the available evidence for the
      epigenetic regulation of these genes.

PMID- 22986024
TI  - Construction and analysis of experimental DNA vaccines against megalocytivirus.
AB  - Iridoviruses are large double-stranded DNA viruses with icosahedral capsid. The
      Iridoviridae family contains five genera, one of which is Megalocytivirus.
      Megalocytivirus has emerged in recent years as an important pathogen to a wide
      range of marine and freshwater fish. In this study, we aimed at developing
      effective genetic vaccines against megalocytivirus affecting farmed fish in
      China. For this purpose, we constructed seven DNA vaccines based on seven genes
      of rock bream iridovirus isolate 1 from China (RBIV-C1), a megalocytivirus with a
      host range that includes Japanese flounder (Paralichthys olivaceus) and turbot
      (Scophthalmus maximus). The protective potentials of these vaccines were examined
      in a turbot model. The results showed that after vaccination via intramuscular
      injection, the vaccine plasmids were distributed in spleen, kidney, muscle, and
      liver, and transcription of the vaccine genes and production of the vaccine
      proteins were detected in these tissues. Following challenge with a lethal-dose
      of RBIV-C1, fish vaccinated with four of the seven DNA vaccines exhibited
      significantly higher levels of survival compared to control fish. Of these four
      protective DNA vaccines, pCN86, which is a plasmid that expresses an 86-residue
      viral protein, induced the highest protection. Immunological analysis showed that
      pCN86 was able to (i) stimulate the respiratory burst of head kidney macrophages
      at 14 d, 21 d, and 28 d post-vaccination, (ii) upregulate the expression of
      immune relevant genes involved in innate and adaptive immunity, and (iii) induce
      production of serum antibodies that, when incubated with RBIV-C1 before
      infection, significantly reduced viral loads in kidney and spleen following viral
      infection of turbot. Taken together, these results indicate that pCN86 is an
      effective DNA vaccine that may be used in the control of megalocytivirus
      associated diseases in aquaculture.

PMID- 22986025
TI  - [Role of in vivo confocal microscopy in irido-corneo-endothelial syndromes].
AB  - INTRODUCTION: In vivo confocal microscopy (IVCM) is an increasingly utilized tool
      in studying complex corneal and anterior segment pathologies. We illustrate the
      role of this imaging technique in the irido-corneo-endothelial (ICE) syndromes
      through a case report. CASE REPORT: A 47-year-old woman presented unilateral
      decreased vision associated with ocular hypertension and peripheral anterior
      synechiae. Slit lamp examination of the cornea was unremarkable but IVCM showed
      pleomorphism and polymegathism of the corneal endothelium and highly reflective
      nuclei resulting in an epithelial-like cell morphology. This appearance led to
      the diagnosis of ICE syndrome. DISCUSSION: Confocal microscopic findings in ICE
      syndromes are similar to histopathologic findings. This technique may be for a
      useful diagnostic adjunct in ICE syndromes by revealing specific characteristics,
      particularly in difficult diagnostic situations, such as when corneal edema
      impedes specular microscopy or when the iris fails to demonstrate pathognomonic
      anomalies.

PMID- 22986026
TI  - [Contextual study of Airsoft gun related ocular injuries].
AB  - INTRODUCTION: Airsoft guns have become more common in France since the Decree of
      March 24, 1999, allowing people over 18 years of age to use weapons with an
      energy level below 2J. The present study aimed to assess the relationship between
      the context of Airsoft gun pellet related ocular injuries and their clinical
      consequences, in order to determine an effective prevention strategy. METHODS: A
      retrospective analysis of ocular injuries due to Airsoft gun pellets was
      conducted in two hospitals in northern France between September 2009 and August
      2010. RESULTS: Six patients with a mean age of 12.6 +/- 3.2 years were included.
      The most frequent injuries were corneal abrasion, hyphema and iris trauma.
      Functional sequelae were observed in 50% of cases and surgical intervention was
      necessary in one third of cases. A direct shot had occurred in all cases. In 83%
      of cases, the accident took place while playing in or around the house. In one
      out of every two cases, the gun had been won at a booth in a fair or had been
      purchased in a big-box store and in no cases did the patients own safety glasses.
      CONCLUSION: The strong appeal of Airsoft guns to minors leads us to propose
      several practical measures to help protect them, with the main one being to
      forbid selling these guns outside of specialized stores.

PMID- 22986027
TI  - [Optic neuropathy and meningioma: a diagnostic trap].
AB  - INTRODUCTION: Meningiomas are benign primary meningeal tumors. Their diagnosis
      may be incidental or in response to a work-up for neurological or
      ophthalmological symptoms. PATIENTS AND METHODS: The clinical course of five
      patients with ophthalmological symptoms leading to the diagnosis of meningioma is
      described. RESULTS: The case reports consist of five women (48 to 54 years old -
      mean 52 years at the onset of symptoms), all suffering from a progressive
      unilateral decrease in visual acuity with a normal initial fundus examination and
      ipsilateral visual field changes. Ancillary testing, in particular MRI and CT
      scans, had to be repeated to make the diagnosis of meningioma, which was delayed
      from 18 months to 4 years. DISCUSSION: The clinical presentation of these five
      cases was that of a retrobulbar optic neuropathy, which biased the work-up
      towards an inflammatory disease of the central nervous system such as multiple
      sclerosis. However, the atypical character of the neuropathy, which did not
      respond to intravenous steroids, caused the diagnosis to be questioned and
      radiological examinations repeated. The iso-intense appearance of meningiomas on
      T1 MR imaging and only slightly hyperintense appearance on T2 may result in a
      diagnostic delay if the exam is not performed and interpreted by an experienced
      professional. Gadolinium contrast, fat suppression and centration on the anterior
      visual pathways are essential to a proper MRI examination. CONCLUSION: When
      confronted with a progressive, painless optic neuropathy unresponsive to steroid
      treatment, the diagnosis of meningioma of the anterior visual pathways must be
      considered. This diagnosis is enabled by a targeted MRI of the anterior visual
      pathways.

PMID- 22986028
TI  - Circular dichroism and anomeric configuration assignment of benzimidazole C
      nucleoside analogs.
AB  - The circular dichroism of a series of acyclic polyhydroxyalkyl benzimidazole C
      nucleoside analogs was correlated with the stereochemistry of the chiral carbon
      atom alpha to the benzimidazole base moiety. This correlation was used for the
      assignment of the anomeric configuration of 2-(beta-L-erythrofuranosyl)
      benzimidazole C-nucleoside analogs without a need to have the other anomer on
      hand, in a similar manner to the correlation obtained for assignment of the
      anomeric configuration of triazole C-nucleoside analogs.

PMID- 22986029
TI  - Studies on the sialylation of galactoses with different C-5 modified sialyl
      donors.
AB  - Synthetic sialylated glycans provide useful tools to study carbohydrate-mediated
      biological recognition; however chemical sialylation is the most challenging
      practice in preparative carbohydrate chemistry, which is often associated with
      low yields and poor stereoselectivity. Herein, we conducted extensive studies on
      sialylation with five types of 5-N-modified sialyl donors and four types of
      galactosyl acceptors. Our studies have shown that a good combination between the
      donor and the acceptor seems necessary to achieve high yield and
      stereoselectivity. None of the donors or acceptors showed 'universal' utility
      toward the sialylation reaction.

PMID- 22986030
TI  - TachoSil Sealed Tubeless Percutaneous Nephrolithotomy to Reduce Urine Leakage and
      Bleeding: Outcome of a Randomized Controlled Study.

PMID- 22986031
TI  - Experience with glycerin for antegrade continence enema in patients with
      neurogenic bowel.
AB  - PURPOSE: Malone antegrade continence enemas are used in the management of
      neurogenic bowel to attain fecal continence. Several different irrigation
      solutions have been described but glycerin, an osmotic laxative that promotes
      peristalsis, has rarely been mentioned or studied. We assessed clinical outcomes
      in our patients with a Malone antegrade continence enema using glycerin based
      irrigation. MATERIALS AND METHODS: We retrospectively reviewed patients with
      neurogenic bowel who underwent a Malone antegrade continence enema procedure
      between 1997 and 2011. Glycerin diluted with tap water followed by a tap water
      flush is our preferred irrigation protocol. Bowel regimen outcomes examined
      included fecal continence, emptying time, leakage from stoma, enema volume,
      frequency and independence. RESULTS: Of the 23 patients with followup greater
      than 6 months 19 used glycerin based irrigation. Average age at surgery was 8.8
      years. Patients using glycerin instilled a median of 30 ml (mean 29) glycerin and
      50 ml (131) tap water. Fecal continence rate was 95% and stoma leakage rate was
      16%, and only 16% of patients required daily irrigation. CONCLUSIONS: Glycerin is
      a viable and effective alternative irrigant for antegrade enemas of neurogenic
      bowel, with an excellent fecal continence rate. The volume of irrigant needed is
      typically less than 90 ml, which is much less than in published reports using tap
      water alone.

PMID- 22986032
TI  - Evaluation of differential renal function and renographic patterns in patients
      with dietl crisis.
AB  - PURPOSE: We analyzed preoperative and postoperative differential renal function
      and characterized the renographic findings in patients with ureteropelvic
      junction obstruction associated with Dietl crisis. MATERIALS AND METHODS:
      Patients with Dietl crisis who underwent pyeloplasty between January 2004 and
      December 2010 were classified by renographic presentation. Patients in group 1
      were diagnosed with cortical retention, those in group 2 had an initial
      obstructed scan (T1/2 of 20 minutes or more and no cortical retention) and those
      in group 3 had an initial nondiagnostic scan (T1/2 of less than 20 minutes and no
      cortical retention). Renographic parameters were used to analyze each group.
      RESULTS: A total of 59 patients met criteria for study inclusion. The 13 patients
      in group 1 demonstrated the most significant recovery of function after
      pyeloplasty (mean differential renal function change 13.59%). The 38 patients in
      group 2 exhibited a mean differential renal function change of 43.06% (range 20%
      to 54.6%) and mean preoperative T1/2 of 64.31 minutes. Pyeloplasty was performed
      in all 8 patients in group 3 based on subsequent diagnostic scan (4 patients) or
      increased hydronephrosis on other imaging associated with further symptomatic
      episodes (4). Initial renographic patterns noted in group 3 included biphasic
      curves, diminished clearance after 15 minutes upright or symptoms despite
      nonobstructive drainage. CONCLUSIONS: Interpretation of diuretic renography
      requires the assimilation of multiple parameters since patients with Dietl crisis
      can exhibit variability in renographic patterns due to the intermittent nature of
      ureteropelvic junction obstruction. Cortical retention represents a specific and
      pathognomic finding of acute ureteropelvic junction obstruction. With appropriate
      evaluation of these parameters, obstruction can be reliably diagnosed and
      appropriate surgical candidates chosen.

PMID- 22986033
TI  - Re: TachoSil(r) sealed tubeless percutaneous nephrolithotomy to reduce urine
      leakage and bleeding: outcome of a randomized controlled study: L. Cormio, A.
      Perrone, G. Di Fino, N. Ruocco, M. De Siati, J. de la Rosette and G. Carrieri J
      Urol 2012;188:145-150.

PMID- 22986034
TI  - Re: antibiotic prophylaxis for shock wave lithotripsy in patients with sterile
      urine before treatment may be unnecessary: a systematic review and meta-analysis:
      Y. Lu, F. Tianyong, H. Ping, L. Liangren, Y. Haichao and W. Qiang J Urol
      2012;188:441-448.

PMID- 22986035
TI  - Half of Visible and Half of Recurrent Visible Hematuria Cases have Underlying
      Pathology: Prospective Large Cohort Study with Long-Term Follow-Up.

PMID- 22986036
TI  - Holmium Laser Enucleation Versus Photoselective Vaporization for Prostatic
      Adenoma Greater than 60 ML: Preliminary Results of a Prospective, Randomized
      Clinical Trial.

PMID- 22986037
TI  - Obstetric Complications of Ureteroscopy During Pregnancy.

PMID- 22986038
TI  - Re: half of visible and half of recurrent visible hematuria cases have underlying
      pathology: prospective large cohort study with long-term followup: S. F.
      Mishriki, R. Vint and B. K. Somani J Urol 2012;187:1561-1565.

PMID- 22986039
TI  - Persistent histological changes in the exstrophic bladder after primary closure-a
      cause for concern?
AB  - PURPOSE: We investigated bladder biopsies from patients with classic bladder
      exstrophy for the histological features and discuss the potential clinical
      significance of the findings. MATERIALS AND METHODS: Bladder tissues were
      collected from patients with bladder exstrophy between 2004 and 2011. These
      specimens were obtained at primary bladder closure (group 1, 29 patients), during
      secondary reconstructive procedures (group 2, 27) or during cystectomy for failed
      reconstruction (group 3, 15). All tissue specimens were investigated for
      inflammatory, proliferative, metaplastic and dysplastic changes. Expression of
      urothelial differentiation markers CK13 and CK20 was determined by
      immunohistochemical analysis. RESULTS: Inflammatory, proliferative and
      metaplastic changes were found in bladder specimens of all subgroups. Neither
      dysplasia nor neoplasia was present. Severe epithelial changes such as cystitis
      glandularis and intestinal metaplasia were observed in up to 62% of bladders
      several years after primary closure. Aberrant expression patterns of CK13 and
      CK20 suggesting abnormal urothelial differentiation were shown to be present in
      the urothelium of all subgroups. CONCLUSIONS: Our findings provide prima facie
      evidence that the epithelial changes observed in the unclosed bladder template
      persist or even progress in a subset of bladders after primary closure. Although
      the malignant potential of cystitis glandularis and intestinal metaplasia is
      controversial, some patients may be at increased risk for dysplasia/neoplasia in
      the long term. Since the natural history of these lesions in the exstrophic
      bladder is unknown, these patients require lifelong surveillance.

PMID- 22986040
TI  - Re: obstetric complications of ureteroscopy during pregnancy: E. B. Johnson, A.
      E. Krambeck, W. M. White, E. Hyams, j. Beddies, T. Marien, O. Shah, B. Matlaga
      and V. M. Pais, jr. J urol 2012;188:151-154.

PMID- 22986041
TI  - Re: Antibiotic Prophylaxis for Shock Wave Lithotripsy in Patients with Sterile
      Urine Before Treatment May be Unnecessary: A Systematic Review and Meta-Analysis.

PMID- 22986042
TI  - Re: Holmium laser enucleation versus photoselective vaporization for prostatic
      adenoma greater than 60 ml: preliminary results of a prospective, randomized
      clinical trial: H. Elmansy, A. Baazeem, A. Kotb, H. Badawy, E. Riad, A. Emran and
      M. Elhilali J Urol, 2012;188:216-221.

PMID- 22986043
TI  - Antibiotic Prophylaxis for Shock Wave Lithotripsy in Patients with Sterile Urine
      Before Treatment May be Unnecessary: A Systematic Review and Meta-Analysis.

PMID- 22986044
TI  - The Community Assessment of Psychic Experience (CAPE) questionnaire as a
      screening-instrument in the detection of individuals at ultra-high risk for
      psychosis.
AB  - Recent findings on intervention options in individuals at ultra-high risk (UHR)
      for psychosis underline the necessity of a screening tool that facilitates early
      detection in low-threshold, non-specialized settings. The aim of this study was
      to examine, whether the Community Assessment of Psychic Experience (CAPE) could
      be used as a screening tool to detect individuals at an increased risk for
      developing psychosis in a clinical, help-seeking population. The utility of the
      CAPE was assessed against the Comprehensive Assessment of At-Risk Mental States
      (CAARMS). The CAPE is a 42-item self-report questionnaire that proved to be
      stable, reliable and valid for self reported psychotic-like experiences in the
      general population. 165 individuals between 13 and 24years of age were assessed
      for being at UHR for developing psychosis. 50.9% individuals were CAARMS-positive
      and 49.1% were CAARMS-negative. The ROC-analysis provided two cut-off points: The
      cut-off value of 3.20 in the positive dimension showed a sensitivity of 67%, a
      specificity of 73%, a positive predictive value of 72% and a negative predictive
      value of 68%. The cut-off value of 2.80 in the positive dimension showed a higher
      sensitivity (83%) and a better negative predictive value (74%), but a lower
      specificity (49%) and a reduced positive predictive value (63%). Our results show
      promise that the CAPE is a valid, simple and cost-effective instrument for
      detecting individuals at UHR in a clinical population. It may represent a useful
      screening tool for calling clinicians' attention to subjects with psychotic-like
      experiences.

PMID- 22986045
TI  - Alexithymia and reduced white matter integrity in schizophrenia: a diffusion
      tensor imaging study on impaired emotional self-awareness.
AB  - Alexithymia is characterized by deficits in emotional self-awareness. A number of
      previous studies have revealed impaired emotional self-awareness in
      schizophrenia. Although the pathology of schizophrenia is thought to involve
      disrupted white matter integrity, its relationship with alexithymia remains
      unclear. The present study investigated associations between alexithymia and
      white matter integrity, to seek the neural basis of impaired emotional self
      awareness in schizophrenia. Forty-four patients with schizophrenia and 44 age-,
      gender- and predicted IQ level-matched healthy controls underwent diffusion
      weighted imaging. Alexithymia was assessed using the 20-item Toronto Alexithymia
      Scale (TAS-20). We applied tract-based spatial statistics to investigate the
      correlation between the TAS-20 total score and white matter fractional anisotropy
      (FA). TAS-20 scores were significantly higher in patients than in controls. In
      the patient group only, FA was negatively correlated with the TAS-20 total score
      in the corpus callosum, mostly the left part of the superior and inferior
      longitudinal fasciculi, the inferior occipito-frontal fasciculus, the anterior
      and posterior thalamic radiation, and the precuneus white matter. These results
      suggest that schizophrenia is associated with alexithymia, and that reduced white
      matter integrity within these regions constitutes an important pathology
      underlying impaired self-emotional awareness in schizophrenia.

PMID- 22986046
TI  - Absence of de novo point mutations in exons of GRIN2B in a large schizophrenia
      trio sample.

PMID- 22986048
TI  - The principle of coherence in multi-level brain information processing.
AB  - Synchronisation has become one of the major scientific tools to explain
      biological order at many levels of organisation. In systems neuroscience,
      synchronised subthreshold and suprathreshold oscillatory neuronal activity within
      and between distributed neuronal assemblies is acknowledged as a fundamental mode
      of neuronal information processing. Coherent neuronal oscillations correlate with
      all basic cognitive functions, mediate local and long-range neuronal
      communication and affect synaptic plasticity. However, it remains unclear how the
      very fast and complex changes of functional neuronal connectivity necessary for
      cognition, as mediated by dynamic patterns of neuronal synchrony, could be
      explained exclusively based on the well-established synaptic mechanisms. A
      growing body of research indicates that the intraneuronal matrix, composed of
      cytoskeletal elements and their binding proteins, structurally and functionally
      connects the synapses within a neuron, modulates neurotransmission and memory
      consolidation, and is hypothesised to be involved in signal integration via
      electric signalling due to its charged surface. Theoretical modelling, as well as
      emerging experimental evidence indicate that neuronal cytoskeleton supports
      highly cooperative energy transport and information processing based on molecular
      coherence. We suggest that long-range coherent dynamics within the intra- and
      extracellular filamentous matrices could establish dynamic ordered states,
      capable of rapid modulations of functional neuronal connectivity via their
      interactions with neuronal membranes and synapses. Coherence may thus represent a
      common denominator of neurophysiological and biophysical approaches to brain
      information processing, operating at multiple levels of neuronal organisation,
      from which cognition may emerge as its cardinal manifestation.

PMID- 22986047
TI  - Ectopic and reentrant activation patterns in the posterior left atrium during
      stretch-related atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in
      humans and is predicted to dramatically increase its prevalence in the future.
      There is experimental evidence that increasing stretch increases the dominance of
      the pulmonary veins (PVs) during AF in isolated hearts and ectopic activity in
      the isolated PVs, but the ionic mechanisms underlying such effects are not clear
      and the ability of the PVs to favorably host functional reentry during stretch
      cannot be excluded. We used a combination of endocardial-epicardial optical
      mapping with phase and spectral analysis to study stretch-related AF (SRAF) in
      normal isolated sheep hearts. We have found rapid AF sources in the posterior
      left atrium (PLA) and PV region and their activation frequency and level of
      organization correlated with intra-atrial pressure. Analysis of the surfaces'
      optical mapping data in the phase domain reveals that activation of the PLA
      consisted of alternating patterns of breakthroughs, reentries and relatively
      simple waves swiping across the mapped field. The patterns on the endocardial and
      epicardial PLA surface at any given moment of time of the SRAF could be either
      identical or not identical, and the activity in the thickness of the PLA wall is
      hypothesized to conform to either ectopic discharge or scroll waves, but a
      definite evidence for the presence of such mechanisms is currently lacking. Thus
      the understanding of the manner by which the mechano-electric feedback effects in
      the PLA, including the PVs, become important in the initiation and maintenance of
      AF requires further detailed investigation.

PMID- 22986049
TI  - Pathogenic role of HIF-1alpha in prostate hyperplasia in the presence of chronic
      inflammation.
AB  - Benign prostatic hyperplasia (BPH) commonly occurs in older men with chronic
      prostatitis. Although BPH is frequently accompanied by inflammation, it is
      unclear whether inflammation underlies prostate enlargement. Recently, we
      reported that hypoxia-inducible factor 1alpha (HIF-1alpha), which is known to be
      induced by proinflammatory cytokines, is involved in testosterone-induced
      prostate hyperplasia. Therefore, we hypothesized that cytokines secreted from
      infiltrated macrophages under inflammatory conditions stimulate prostate
      enlargement by up-regulating HIF-1alpha. In the present study, we injected
      lipopolysaccharide (LPS) into rat prostates to mimic prostatitis and evaluated
      prostate hyperplasia 14days later. Epithelial cells of LPS-treated prostates were
      found to be highly proliferative and HIF-1alpha levels in prostate tissues to be
      elevated. When prostate epithelial cells were incubated in conditioned medium
      from macrophages activated with LPS, they robustly expressed HIF-1alpha, and
      under these conditions IL-1beta, IL-6, and TNF-alpha cytokines were found to
      mediate HIF-1alpha induction. In addition, HIF-1alpha was found to enhance the
      expression of Twist, which initiates epithelial-mesenchymal transition (EMT).
      Furthermore, profound EMT features were observed in LPS-treated rat prostates,
      and the natural HIF-1alpha inhibitors ascorbate and curcumin were found to
      attenuate EMT and prostate hyperplasia both in vivo and in vitro. Based on these
      results, we propose that HIF-1alpha mediates prostate enlargement under
      inflammatory conditions, and we suggest that HIF-1alpha be viewed as a promising
      target for blocking the transition from prostatitis to BPH.

PMID- 22986051
TI  - Effect of PEG-200 and Tween-20 on photoisomerization of 1-alkyl-2
      (arylazo)imidazoles in toluene.
AB  - The photoisomerization of 1-alkyl-2-(arylazo)imidazole, trans-to-cis, has been
      studied in the matrix of PEG-200 and Tween-20 in toluene medium by UV light
      irradiation. The trans and cis-isomers have different absorption spectra. The cis
      to-trans isomerization proceeds slowly in visible light irradiation while it is
      appreciably fast in thermal process. The rate of trans-to-cis isomerization is
      decreased by 30-60% in presence of PEG-200 and Tween-20. The quantum yield of the
      photoisomerization is also decreased by 35-55% and follows the rate sequence:
      free state>PEG-200-phase>Tween-20 phase. The activation energy (E(a)) of cis
      >trans, thermal backward isomerization, is reduced in PEG-200 and Tween-20 phase
      following free state>PEG-200-phase>Tween-20-phase. The branched polyhydroxo
      structure of Tween-20 may help to wrap the polar photochrome more efficiently
      than major ether functionalized PEG-200 and stabilizes trans-isomer.

PMID- 22986050
TI  - FT-IR spectral, DFT studies and detailed vibrational assignment on N,N',N"-tris(2
      aminoethyl)-phosphoric acid triamide.
AB  - Structure of N,N',N"-tris(2-aminoethyl)-phosphoric acid triamide (TEDAP), which
      is a phosphorus-containing reactive amine crosslinking agent and flame retardant
      material as well, identified by Fourier transform infrared (FT-IR) spectroscopy
      and quantum chemical calculations. The FT-IR spectrum of TEDAP, being a recently
      synthesized new compound, has been recorded in the 4000-650 cm(-1) region for the
      first time. The molecular geometry and vibrational wavenumbers of the compound in
      its ground state have been calculated by using Density Functional Theory (DFT)
      using B3LYP functional with 6-311++G(d,p) basis set. All calculations were
      performed with Gaussian09 software. The obtained vibrational wavenumbers and
      optimized geometric parameters were seen to be in good agreement with the
      experimental data. Furthermore, assignments of each vibrational mode were
      interpreted in terms of potential energy distributions (PED) in detail.

PMID- 22986052
TI  - Study of the solvent effects on the molecular structure and CO stretching
      vibrations of flurbiprofen.
AB  - The effects of 15 solvents on the C=O stretching vibrational frequency of
      flurbiprofen (FBF) were determined to investigate solvent-solute interactions.
      Solvent effects on the geometry and C=O stretching vibrational frequency,
      nu(C=O), of FBF were studied theoretically at the DFT/B3LYP and HF level in
      combination with the polarizable continuum model and experimentally using
      attenuated total reflection infrared spectroscopy (ATR-IR). The calculated C=O
      stretching frequencies in the liquid phase are in agreement with experimental
      values. Moreover, the wavenumbers of nu(C=O) of FBF in different solvents have
      been obtained and correlated with the Kirkwood-Bauer-Magat equation (KBM), the
      solvent acceptor numbers (ANs), and the linear solvation energy relationships
      (LSERs). The solvent-induced stretching vibrational frequency shifts displayed a
      better correlation with the LSERs than with the ANs and KBM.

PMID- 22986053
TI  - Experimental (FT-IR and FT-RS) and theoretical (QC-DFT) studies of vibrational
      modes and molecular structure of new low-temperature phases of [Ru(NH3)6](BF4)3
      and [Ru(NH3)6](ClO4)3.
AB  - Vibrational spectra of [Ru(NH(3))(6)](BF(4))(3) and [Ru(NH(3))(6)](ClO(4))(3) in
      their novel low-temperature solid phases were recorded using FT-IR and FT-RS.
      Quantum chemical calculations of molecular structure and vibrational modes were
      made separately for BF(4)(-),ClO(4)(-)and[Ru(NH(3))(6)](3+) ions. The harmonic
      vibrational frequencies and the related IR and RS bands intensities and
      activities, respectively, were simulated at the B3LYP/6-311+G(d) and
      B3LYP/LANL2TZ(f)/6-311+G(d,p) levels of the DFT. Full interpretation of the
      vibrational spectra has been carried out with the aid of the normal coordinate
      analysis. The assignments of the vibrational modes were based on the potential
      energy distribution data, using the MOLVIB program. The calculated Ru-N
      stretching frequencies are too low, in comparison to experiment, which indicates
      that B3LYP method underestimates the Ru-N bond strength. Some values of
      calculated and measured (obtained from X-ray) bond lengths and angles were also
      compared. Conclusions about possible interactions inside and between the complex
      ions were drawn.

PMID- 22986054
TI  - Resveratrol attenuates experimental allergic asthma in mice by restoring inositol
      polyphosphate 4 phosphatase (INPP4A).
AB  - Asthma is a chronic airway inflammatory disorder which is characterized by
      reversible airway obstruction, airway hyperresponsiveness and airway
      inflammation. Oxidative stress has been shown to be strongly associated with most
      of the features of asthma and leads to accumulation of phosphatidyl inositol
      (3,4) bis-phosphate {PtdIns(3,4)P2} which is the major substrate for inositol
      polyphosphate 4 phosphatase (INPP4A). PtdIns(3,4)P2 in turn activates PI3K
      pathway and contributes to oxidative stress. Thus, there exists a vicious loop
      between oxidative stress and lipid phosphatase signaling. In this context, we
      have recently shown that INPP4A, a crucial molecular checkpoint in controlling
      PI3K-Akt signaling pathway, is downregulated in allergic airway inflammation.
      Resveratrol, a potent antioxidant found in red wines, has been shown to attenuate
      asthma features in murine model of allergic airway inflammation (AAI), however
      the underlying mode of its action was not completely understood. In this study,
      the effect of resveratrol on mitochondrial dysfunction, PI3K-Akt signaling and
      inositol polyphosphate 4 phosphatase was studied in murine model of allergic
      airway inflammation. We observed that resveratrol treatment of allergic mice was
      found to significantly downregulate oxidative stress and restore mitochondrial
      function. It also decreased calpain activity and restored the expression of
      INPP4A in lungs which in turn reduced Akt kinase activity and Akt
      phosphorylation. These results suggest a novel mechanism of action of resveratrol
      in attenuating asthma phenotype by downregulating PI3K-Akt pathway via
      upregulating INPP4A.

PMID- 22986055
TI  - Bluetongue virus serotype 26: infection kinetics, pathogenesis and possible
      contact transmission in goats.
AB  - The aim of this study was to assess the pathogenicity and infection kinetics of
      Bluetongue virus serotype 26 (BTV-26) in goats. Out of a group of six goats
      housed in insect free accommodation, five were experimentally infected with BTV
      26 and one was kept uninfected as an in-contact control. Samples taken throughout
      the study were used to determine the kinetics of infection using a pan specific
      BTV real time RT-PCR assay and a group specific ELISA. The five infected goats
      did not show clinical signs of BTV, however high levels of viral RNA were
      detected and virus was isolated from the blood of all 5 goats. Antibodies against
      BTV were first detected between 7 and 11 dpi in all 5 experimentally infected
      goats. Interestingly at 21 dpi viral RNA was detected in, and virus was isolated
      from, the blood of the in-contact control goat, which also seroconverted. These
      results suggest that BTV-26 replicates to high levels in goats, causing no
      obvious clinical disease, suggesting that goats may be the natural host for this
      virus. Preliminary evidence also indicates that BTV-26 may be spread by contact
      transmission between goats, however a more detailed study is required in order to
      confirm this observation.

PMID- 22986056
TI  - The OmpA family of proteins: roles in bacterial pathogenesis and immunity.
AB  - The OmpA family of outer membrane proteins is a group of genetically related,
      heat-modifiable, surface-exposed, porin proteins that are in high-copy number in
      the outer membrane of mainly Gram-negative bacteria. OmpA proteins are
      characterized by an N-terminal domain that forms an eight-stranded, anti-parallel
      beta barrel, which is embedded in the outer membrane. The C-terminal domain is
      globular and located in the periplasmic space. Escherichia coli OmpA is the best
      characterized of the proteins. Other well-characterized OmpA-equivalent proteins
      from pathogenic bacteria include Pseudomonas aeruginosa OprF, Haemophilus
      influenzae P5, Klebsiella pneumoniae OmpA, and Chlamydia trachomatis major outer
      membrane protein (MOMP). OmpA from the veterinary pathogens Mannheimia
      haemolytica, Haemophilus parasuis, Leptospira interrogans, and Pasteurella
      multocida have been studied to a lesser extent. Among many of the pathogenic
      bacteria, OmpA proteins have important pathogenic roles including bacterial
      adhesion, invasion, or intracellular survival as well as evasion of host defenses
      or stimulators of pro-inflammatory cytokine production. These pathogenic roles
      are most commonly associated with central nervous system, respiratory and
      urogenital diseases. Alternatively, OmpA family proteins can serve as targets of
      the immune system with immunogenicity related to surface-exposed loops of the
      molecule. In several cases, OmpA proteins are under evaluation as potential
      vaccine candidates.

PMID- 22986057
TI  - Experimental infection of weaned piglets with Campylobacter coli--excretion and
      translocation in a pig colonisation trial.
AB  - Campylobacter (C.) is one of the most common food-borne pathogen causing
      bacterial enteric infections in humans. Consumption of meat and meat products
      that have been contaminated with Campylobacter are the major source of infection.
      Pigs are a natural reservoir of Campylobacter spp. with C. coli as the dominant
      species. Even though some studies focussed on transmission of C. coli in pig
      herds and the excretion in faeces, little is known about the colonisation and
      excretion dynamics of C. coli in a complex gut microbiota present in weaned
      piglets and the translocation to different tissues. Therefore, an experimental
      trial was conducted to evaluate the colonisation and translocation ability of the
      porcine strain C. coli 5981 in weaned pigs. Thus, ten 35 days old piglets were
      intragastrically inoculated with strain C. coli 5981 (7 * 10(7)CFU/animal)
      encoding resistances against erythromycin and neomycin. Faecal samples were taken
      and C. coli levels were enumerated over 28 days. All piglets were naturally
      colonised with C. coli before experimental inoculation, and excretion levels
      ranged from 10(4) to 10(7)CFU/g faeces. However, no strain showed resistances
      against the additional antimicrobials used. Excretion of C. coli 5981 was seen
      for all piglets seven days after inoculation and highest counts were detectable
      ten days after inoculation with 10(6)CFU/g faeces. Post-mortem, translocation and
      subsequent invasion of luminal C. coli was observed for gut tissues of the small
      intestine and for the gut associated lymphatic tissues, such as jejunal
      mesenteric lymph nodes and tonsils as well as for spleen and gall bladder. In
      conclusion, this pig colonisation trial offers the opportunity to study C. coli
      colonisation in weaned piglets using the porcine strain C. coli 5981 without the
      need for gnotobiotic or specific pathogen-free animals.

PMID- 22986059
TI  - Foreword: oropharynx cancer.

PMID- 22986058
TI  - Identification of BACE2 as an avid beta-amyloid-degrading protease.
AB  - BACKGROUND: Proteases that degrade the amyloid beta-protein (Abeta) have emerged
      as key players in the etiology and potential treatment of Alzheimer's disease
      (AD), but it is unlikely that all such proteases have been identified. To
      discover new Abeta-degrading proteases (AbetaDPs), we conducted an unbiased,
      genome-scale, functional cDNA screen designed to identify proteases capable of
      lowering net Abeta levels produced by cells, which were subsequently
      characterized for Abeta-degrading activity using an array of downstream assays.
      RESULTS: The top hit emerging from the screen was beta-site amyloid precursor
      protein-cleaving enzyme 2 (BACE2), a rather unexpected finding given the well
      established role of its close homolog, BACE1, in the production of Abeta. BACE2
      is known to be capable of lowering Abeta levels via non-amyloidogenic processing
      of APP. However, in vitro, BACE2 was also found to be a particularly avid
      AbetaDP, with a catalytic efficiency exceeding all known AbetaDPs except insulin
      degrading enzyme (IDE). BACE1 was also found to degrade Abeta, albeit ~150-fold
      less efficiently than BACE2. Abeta is cleaved by BACE2 at three peptide bonds
      Phe19-Phe20, Phe20-Ala21, and Leu34-Met35--with the latter cleavage site being
      the initial and principal one. BACE2 overexpression in cultured cells was found
      to lower net Abeta levels to a greater extent than multiple, well-established
      AbetaDPs, including neprilysin (NEP) and endothelin-converting enzyme-1 (ECE1),
      while showing comparable effectiveness to IDE. CONCLUSIONS: This study identifies
      a new functional role for BACE2 as a potent AbetaDP. Based on its high catalytic
      efficiency, its ability to degrade Abeta intracellularly, and other
      characteristics, BACE2 represents a particulary strong therapeutic candidate for
      the treatment or prevention of AD.

PMID- 22986060
TI  - Oropharynx cancer.

PMID- 22986062
TI  - Continuous passive oxygen insufflation for out-of-hospital cardiac arrest: a
      systemic review of clinical studies.

PMID- 22986061
TI  - Females of childbearing age have a survival benefit after out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: There is controversy regarding the association between age and being
      female and survival to hospital discharge after out-of-hospital cardiac arrest
      (OHCA). We hypothesized that younger females (aged 12-49 years) would be
      independently associated with increased survival after OHCA when compared to
      other age and sex groups. METHODS: We conducted a secondary analysis of
      prospectively collected data from 29 United States cities that participate in the
      Cardiac Arrest Registry to Enhance Survival (CARES). Patients were included if
      they were >=12 years of age and had a documented resuscitation attempt from
      October 1, 2005 through December 31, 2009. Hierarchical multivariable logistic
      regression analyses were used to estimate the associations between age and sex
      groups and survival to hospital discharge. RESULTS: Females were less likely to
      have a cardiac arrest in public, was witnessed, or was treatable with
      defibrillation. Females in the 12-49 year old age group had a similar proportion
      of survival to hospital discharge when compared to age-matched males (females
      11.6% vs. males 11.2%), while males >=50 years old were more likely to survive
      when compared to age matched females (females 6.9% vs. males 9.6%). Age
      stratified regression models demonstrated that 12-49 year old females had the
      largest association with survival to hospital discharge (OR 1.55, 95% CI 1.20
      2.00), while females in the >=50 year old age group had a smaller increased odds
      of survival to hospital discharge (OR 1.18, 95% CI 1.03-1.35), which only lasted
      until the age of 55 years (OR 1.12, 95% CI 0.97-1.29). CONCLUSIONS: Younger aged
      females were associated with increased odds of survival despite being found with
      poorer prognostic arrest characteristics.

PMID- 22986064
TI  - Effect of a rescuer's side of approach on their performance of conventional
      cardiopulmonary resuscitation.

PMID- 22986065
TI  - Optimizing oxygenation and ventilation after cardiac arrest in "little adults".

PMID- 22986066
TI  - An assessment of the triage performance of the efferent arm of the rapid response
      system.
AB  - OBJECTIVES: To measure the triage performance of the efferent arm of a rapid
      response system (RRS) by assessing the 24h outcome of patients triaged to remain
      on the ward after rapid response team (RRT) review. METHODS: We performed a
      retrospective observational study of all consecutive RRS activations between
      August 2005 and December 2011 in a university-affiliated hospital. Calls
      involving patients with documented limitations of medical therapy (LOMT) orders
      were excluded. We determined patients who were triaged to stay on the ward at the
      end of their first (index) call and analyzed their vital status and location 24h
      later. Finally, we reviewed medical charts of patients triaged to remain on the
      ward and had a cardiac arrest and/or died within 24h of RRT review. RESULTS: We
      studied 8304 RRT calls. We excluded 1794 calls involving patients with LOMT, 2165
      that were repeat calls, 20 where data was missing, 650 where patients were
      immediately transferred to a high dependency (HDU) or an intensive care unit
      (ICU) and 92 where calls were rapidly upgraded to cardiac arrest calls. Thus, we
      identified 3583 index calls at the end of which patients were triaged to remain
      on the ward. Within 24h, 454 (12.7%) of those had a repeat RRT activation and 378
      were transferred to HDU/ICU. 12 (0.3%) suffered a cardiac arrest on the ward.
      Altogether, 14 (0.4%) patients died within 24h of the index RRT activation. Of
      those 6 had LOMT applied after the call, 4 had been admitted to ICU in a further
      call and 6 (0.2%) patients had unexpected cardiac arrest on the ward.
      CONCLUSIONS: The rate of unexpected cardiac arrest in the 24h following RRT
      activation is very low for patients triaged to stay on the ward. Major triage
      errors by the RRT appear uncommon.

PMID- 22986067
TI  - Pre-hospital body surface potential mapping improves early diagnosis of acute
      coronary artery occlusion in patients with ventricular fibrillation and cardiac
      arrest.
AB  - AIMS: To determine whether 80-lead body surface potential mapping (BSPM) improves
      detection of acute coronary artery occlusion in patients presenting with out-of
      hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) and who
      survived to reach hospital. METHODS AND RESULTS: Of 645 consecutive patients with
      OHCA who were attended by the mobile coronary care unit, VF was the initial
      rhythm in 168 patients. Eighty patients survived initial resuscitation, 59 of
      these having had BSPM and 12-lead ECG post-return of spontaneous circulation
      (ROSC) and in 35 patients (age 69+/-13 yrs; 60% male) coronary angiography
      performed within 24 h post-ROSC. Of these, 26 (74%) patients had an acutely
      occluded coronary artery (TIMI flow grade [TFG] 0/1) at angiography. Twelve-lead
      ECG criteria showed ST-segment elevation (STE) myocardial infarction (STEMI)
      using Minnesota 9-2 criteria--sensitivity 19%, specificity 100%; ST-segment
      depression (STD) >=0.05 mV in >=2 contiguous leads--sensitivity 23%, specificity
      89%; and, combination of STEMI or STD criteria--sensitivity 46%, specificity
      100%. BSPM STE occurred in 23 (66%) patients. For the diagnosis of TFG 0/1 in a
      main coronary artery, BSPM STE had sensitivity 88% and specificity 100% (c
      statistic 0.94), with STE occurring most commonly in either the posterior, right
      ventricular or high right anterior territories. CONCLUSION: Among OHCA patients
      presenting with VF and who survived resuscitation to reach hospital, post
      resuscitation BSPM STE identifies acute coronary occlusion with sensitivity 88%
      and specificity 100% (c-statistic 0.94).

PMID- 22986068
TI  - Emergency medical helicopter operations for avalanche accidents.
AB  - BACKGROUND: In the European Alps emergency medical helicopter services are
      regularly involved in avalanche rescue missions. How the helicopter emergency
      medical system best supports avalanche rescue missions is controversial. AIM OF
      THE STUDY: To study advantages and limitations of the early dispatch of emergency
      medical helicopters after avalanche accidents. METHODS: Data on rescue mission
      characteristics and patterns and severity of medical emergencies were obtained
      for 221 helicopter avalanche rescue missions performed in the Austrian province
      of Tyrol between October 2008 and June 2011. RESULTS: A buried avalanche victim
      had to be searched for in only 12 (5.5%) of the 221 rescue missions, whereas
      medical emergencies were encountered at the scene in 24 missions (11%). Survival
      rate for totally buried victims extricated after helicopter arrival was
      significantly lower than for victims extricated before helicopter arrival (19%
      versus 74%, p=0.0002). In 124 missions (56%) no victim was present at the scene
      when the helicopter arrived. Medical emergencies involved normothermic cardiac
      arrest (n=11), severe accidental hypothermia (n=6), critical trauma (n=7) and
      hypothermia combined with critical trauma (n=1). Survival rate at hospital
      discharge was 27% for arrested normothermic patients and 50% for trauma and
      hypothermia patients. CONCLUSIONS: Medical emergencies are encountered at
      avalanche scenes twice as often as there is need to search for totally buried
      victims, clearly supporting the immediate dispatch of medical crew members to the
      accident site. The high rate of emergency medical helicopter operations to
      avalanche incidents where no victim is injured or buried may be characteristic
      for densely populated mountainous regions and can be reduced by a restrictive
      dispatch policy after avalanche accidents without clear information about human
      involvement.

PMID- 22986069
TI  - Which fluid should be used for fluid therapy to protect kidneys in cardiogenic
      shock after cardiac arrest?

PMID- 22986070
TI  - High spontaneous activity of C-nociceptors in painful polyneuropathy.
AB  - Polyneuropathy can be linked to chronic pain but also to reduced pain
      sensitivity. We investigated peripheral C-nociceptors in painful and painless
      polyneuropathy patients to identify pain-specific changes. Eleven polyneuropathy
      patients with persistent spontaneous pain and 8 polyneuropathy patients without
      spontaneous pain were investigated by routine clinical methods. For a specific
      examination of nociceptor function, action potentials from single C-fibres
      including 214 C-nociceptors were recorded by microneurography. Patients with and
      without pain were distinguished by the occurrence of spontaneous activity and
      mechanical sensitization in C-nociceptors. The mean percentage of C-nociceptors
      being spontaneously active or mechanically sensitized was significantly higher in
      patients with pain (mean 40.5% and 14.6%, respectively, P=.02). The difference
      was mainly due to more spontaneously active mechanoinsensitive C-nociceptors
      (operationally defined by their mechanical insensitivity and their axonal
      characteristics) in the pain patients (19 of 56 vs 6 of 43; P=.02). The
      percentage of sensitized mechanoinsensitive C-nociceptors correlated to the
      percentage of spontaneously active mechanoinsensitive C-nociceptors (Kendall's
      tau=.55, P=.004). Moreover, spontaneous activity of mechanoinsensitive C
      nociceptors correlated to less pronounced activity-dependent slowing of
      conduction (Kendall's tau=-.48, P=.009), suggesting that axons were included in
      the sensitization process. Hyperexcitability in mechanoinsensitive C-nociceptors
      was significantly higher in patients with polyneuropathy and pain compared to
      patients with polyneuropathy without pain, while the difference was much less
      prominent in mechanosensitive (polymodal) C-nociceptors. This hyperexcitability
      may be a major underlying mechanism for the pain experienced by patients with
      painful peripheral neuropathy.

PMID- 22986071
TI  - Complications and radiographic outcome of children's both-bone diaphyseal forearm
      fractures after invasive and non-invasive treatment.
AB  - BACKGROUND: The incidence of paediatric forearm fractures and their invasive
      operative treatment is increasing. Evidence supporting increased interest in
      internal fixation of forearm fractures has been controversial. We studied
      radiographic outcome and complications of both-bone diaphyseal middle-third
      forearm fractures according to the type of treatment. The purpose of the study
      was to determine if there is an advantage in invasive treatment over non-invasive
      treatment that supports the increasing trend towards invasive surgery. MATERIALS
      AND METHODS: All children and adolescents (<16 years) with both-bone diaphyseal
      middle-third forearm fractures in a geographic area with 86,000 children in 2000
      2009 were included. There were 168 patients. The types of primary fractures and
      their malalignment and displacement rates were analysed. The fractures were
      classified as 'severe' or 'mild' according to radiographic findings. Radiographic
      fracture healing and alignment and the rate of complications were compared as
      regards invasive versus non-invasive surgery. RESULTS: Just over a third of all
      patients suffered from some complication during follow-up. The overall
      complication rate was highest in the non-invasive treatment group (58%) and
      lowest in the intramedullary nailing group (24%) (P < 0.001). The difference was
      significant as regards both mild and severe fractures. Nearly a third of the
      fractures in the non-invasive treatment group were re-reduced during follow-up.
      Two third of them were finally fixed invasively. Re-reduction after invasive
      fixation was rare (1.4%, P = 0.001). Re-fracture was equally uncommon (7.1%) in
      both the invasive and non-invasive groups. Non-union was unusual (1.2%) and it
      was related to high-energy trauma or chronic disease. Nerve co-morbidity, scar
      problems, soft-tissue complications and compartmental syndrome were not problems
      in the study population despite the type of treatment. CONCLUSIONS: We found that
      the complication rate of diaphyseal forearm fractures was twice as common after
      non-invasive than after invasive treatment. The need of re-reduction after non
      invasive treatment was remarkable. Nevertheless, bone healing was equally good
      despite the treatment. We conclude that intramedullary fixation of both-bone
      forearm fractures is a good mode of primary treatment of mild and severe middle
      third diaphyseal both-bone forearm fractures.

PMID- 22986072
TI  - [Is 9,000 euros the difference between sense and nonsense?].

PMID- 22986073
TI  - The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates
      with bone mineral density in healthy and postmenopausal osteoporotic women.
AB  - INTRODUCTION: The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1)
      plays an important role in the regulation of local glucocorticoid concentration
      in a tissue specific manner. Previous studies indicated associations between
      polymorphisms (SNPs) of the HSD11B1 gene and laboratory as well as
      osteodensitometric parameters of bone metabolism. In our present work we examined
      whether the tagging HSD11B1 gene polymorphisms could influence bone metabolism in
      healthy and postmenopausal osteoporotic women. EXPERIMENTAL: HapMap database was
      used for identification and selection of SNPs located in the 38kb range of the
      HSD11B1 gene. Twelve SNPs were selected and genotyped in 209 healthy control
      women using Taqman SNP assays on Real-Time PCR and direct DNA sequencing. Of
      these SNPs, the rs4844880 was genotyped in 154 women with postmenopausal
      osteoporosis. Functional characterization of the rs4844880 was performed by in
      vitro luciferase assay. RESULTS: One of the 12 HSD11B1 SNPs, the rs4844880 showed
      a significant association with higher bone mineral density and/or T- and Z-scores
      at lumbar spine in healthy women. When data from 154 postmenopausal osteoporotic
      women were compared to those obtained from 101 age-matched postmenopausal healthy
      women selected from our healthy control group this association was strongly
      significant at the femoral neck region. In vitro luciferase assay demonstrated
      that the polymorphic rs4844880 allele inhibited the luciferase activity more
      significantly than the major allele. CONCLUSIONS: The rs4844880 polymorphism in
      the promoter region of the HSD11B1 gene resulting in a reduced expression of the
      enzyme may exert a beneficial effect on bone in healthy and postmenopausal
      osteoporotic women.

PMID- 22986074
TI  - A novel varanic acid epimer--(24R,25S)-3alpha,7alpha,12alpha,24-tetrahydroxy
      5beta-cholestan-27-oic acid--is a major biliary bile acid in two varanid lizards
      and the Gila monster.
AB  - A key intermediate in the biosynthetic pathway by which C(24) bile acids are
      formed from cholesterol has long been considered to be varanic acid, (24xi,25xi)
      3alpha,7alpha,12alpha-24-tetrahydroxy-5beta-cholestan-27-oic acid. The (24R,25R)
      epimer of this tetrahydroxy bile acid, in the form of its taurine N-acyl amidate,
      was thought to be the major biliary bile acid in lizards of the family Varanidae.
      We report here that a major biliary bile acid of three lizard species - the
      Komodo dragon (Varanus komodoensis), Gray's monitor (Varanus olivaceus), and the
      Gila monster (Heloderma suspectum) - is a novel epimer of varanic acid. The
      epimer was shown to be (24R,25S)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta
      cholestan-27-oic acid (present in bile as its taurine conjugate). The structure
      was established by mass spectroscopy and by (1)H and (13)C nuclear magnetic
      spectroscopy, as well as by synthesis of the compound.

PMID- 22986075
TI  - Structure-activity relationship (SAR) analysis of a family of steroids acutely
      controlling steroidogenesis.
AB  - Steroids metabolically derive from lipid cholesterol, and vertebrate steroids
      additionally derive from the steroid pregnenolone. Pregnenolone is derived from
      cholesterol by hydrolytic cleavage of the aliphatic tail by mitochondrial
      cytochrome P450 enzyme CYP11A1, located in the inner mitochondrial membrane.
      Delivery of cholesterol to CYP11A1 comprises the principal control step of
      steroidogenesis, and requires a series of proteins spanning the mitochondrial
      double membranes. A critical member of this cholesterol translocation machinery
      is the integral outer mitochondrial membrane translocator protein (18kDa, TSPO),
      a high-affinity drug- and cholesterol-binding protein. The cholesterol-binding
      site of TSPO consists of a phylogenetically conserved cholesterol
      recognition/interaction amino acid consensus (CRAC). Previous studies from our
      group identified 5-androsten-3beta,17,19-triol (19-Atriol) as drug ligand for the
      TSPO CRAC motif inhibiting cholesterol binding to CRAC domain and
      steroidogenesis. To further understand 19-Atriol's mechanism of action as well as
      the molecular recognition by the TSPO CRAC motif, we undertook structure-activity
      relationship (SAR) analysis of the 19-Atriol molecule with a variety of
      substituted steroids oxygenated at positions around the steroid backbone. We
      found that in addition to steroids hydroxylated at carbon C19, hydroxylations at
      C4, C7, and C11 contributed to inhibition of cAMP-mediated steroidogenesis in a
      minimal steroidogenic cell model. However, only substituted steroids with C19
      hydroxylations exhibited specificity to TSPO, its CRAC motif, and mitochondrial
      cholesterol transport, as the C4, C7, and C11 hydroxylated steroids inhibited the
      metabolic transformation of cholesterol by CYP11A1. We thus provide new insights
      into structure-activity relationships of steroids inhibiting mitochondrial
      cholesterol transport and steroidogenic cholesterol metabolic enzymes.

PMID- 22986076
TI  - A method for event-related phase/amplitude coupling.
AB  - Phase/amplitude coupling (PAC) is emerging as an important electrophysiological
      measure of local and long-distance neuronal communication. Current techniques for
      calculating PAC provide a numerical index that represents an average value across
      an arbitrarily long time period. This requires researchers to rely on block
      design experiments and temporal concatenation at the cost of the sub-second
      temporal resolution afforded by electrophysiological recordings. Here we present
      a method for calculating event-related phase/amplitude coupling (ERPAC) designed
      to capture the temporal evolution of task-related changes in PAC across events or
      between distant brain regions that is applicable to human or animal
      electromagnetic recording.

PMID- 22986077
TI  - Disentangling common and specific neural subprocesses of response inhibition.
AB  - Response inhibition is disturbed in several disorders sharing impulse control
      deficits as a core symptom. Since response inhibition is a cognitively and
      neurally multifaceted function which has been shown to rely on differing neural
      subprocesses and neurotransmitter systems, further differentiation to define
      neurophysiological endophenotypes is essential. Response inhibition may involve
      at least three separable cognitive subcomponents, i.e. interference inhibition,
      action withholding, and action cancelation. Here, we introduce a novel paradigm -
      the Hybrid Response Inhibition task - to disentangle interference inhibition,
      action withholding and action cancelation and their neural subprocesses within
      one task setting during functional magnetic resonance imaging (fMRI). To validate
      the novel task, results were compared to a battery of separate, standard response
      inhibition tasks independently capturing these subcomponents and subprocesses.
      Across all subcomponents, mutual activation was present in the right inferior
      frontal cortex (rIFC), pre-supplementary motor area (pre-SMA) and parietal
      regions. Interference inhibition revealed stronger activation in pre-motor and
      parietal regions. Action cancelation resulted in stronger activation in fronto
      striatal regions. Our results show that all subcomponents share a common neural
      network and thus all constitute different subprocesses of response inhibition.
      Subprocesses, however, differ to the degree of regional involvement: interference
      inhibition relies more pronouncedly on a fronto-parietal-pre-motor network
      suggesting its close relation to response selection processes. Action
      cancelation, in turn, is more strongly associated with the fronto-striatal
      pathway implicating it as a late subcomponent of response inhibition. The new
      paradigm reliably captures three putatively subsequent subprocesses of response
      inhibition and might be a promising tool to differentially assess disturbed
      neural networks in disorders showing impulse control deficits.

PMID- 22986078
TI  - Class-specific weighting for Markov random field estimation: application to
      medical image segmentation.
AB  - Many estimation tasks require Bayesian classifiers capable of adjusting their
      performance (e.g. sensitivity/specificity). In situations where the optimal
      classification decision can be identified by an exhaustive search over all
      possible classes, means for adjusting classifier performance, such as probability
      thresholding or weighting the a posteriori probabilities, are well established.
      Unfortunately, analogous methods compatible with Markov random fields (i.e. large
      collections of dependent random variables) are noticeably absent from the
      literature. Consequently, most Markov random field (MRF) based classification
      systems typically restrict their performance to a single, static operating point
      (i.e. a paired sensitivity/specificity). To address this deficiency, we
      previously introduced an extension of maximum posterior marginals (MPM)
      estimation that allows certain classes to be weighted more heavily than others,
      thus providing a means for varying classifier performance. However, this
      extension is not appropriate for the more popular maximum a posteriori (MAP)
      estimation. Thus, a strategy for varying the performance of MAP estimators is
      still needed. Such a strategy is essential for several reasons: (1) the MAP cost
      function may be more appropriate in certain classification tasks than the MPM
      cost function, (2) the literature provides a surfeit of MAP estimation
      implementations, several of which are considerably faster than the typical Markov
      Chain Monte Carlo methods used for MPM, and (3) MAP estimation is used far more
      often than MPM. Consequently, in this paper we introduce multiplicative weighted
      MAP (MWMAP) estimation-achieved via the incorporation of multiplicative weights
      into the MAP cost function-which allows certain classes to be preferred over
      others. This creates a natural bias for specific classes, and consequently a
      means for adjusting classifier performance. Similarly, we show how this
      multiplicative weighting strategy can be applied to the MPM cost function (in
      place of the strategy we presented previously), yielding multiplicative weighted
      MPM (MWMPM) estimation. Furthermore, we describe how MWMAP and MWMPM can be
      implemented using adaptations of current estimation strategies such as iterated
      conditional modes and MPM Monte Carlo. To illustrate these implementations, we
      first integrate them into two separate MRF-based classification systems for
      detecting carcinoma of the prostate (CaP) on (1) digitized histological sections
      from radical prostatectomies and (2) T2-weighted 4 Tesla ex vivo prostate MRI. To
      highlight the extensibility of MWMAP and MWMPM to estimation tasks involving more
      than two classes, we also incorporate these estimation criteria into a MRF-based
      classifier used to segment synthetic brain MR images. In the context of these
      tasks, we show how our novel estimation criteria can be used to arbitrarily
      adjust the sensitivities of these systems, yielding receiver operator
      characteristic curves (and surfaces).

PMID- 22986079
TI  - How to deal with diplopia.
AB  - Diplopia is a frequent neuro-ophthalmologic symptom with diverse etiologies. This
      article describes elementary diagnostic tests and frequent causes of diplopia.
      Monocular diplopia persists when the other eye is closed and usually disappears
      when the patient looks through a pinhole. It is usually caused by errors in the
      optical media of the eye and has to be differentiated from spectacle-induced side
      effect and non-organic disorders. A sign of non-organic etiology is absence of
      change in image position when the head is tilted. Binocular diplopia disappears
      regardless of which eye is closed. Binocular diplopia occurs when the images of
      both eyes cannot be fused. The most frequent direct cause of diplopia is acquired
      strabismus. Knowledge of several specific types of strabismus enables efficient
      patient management. Congenital and decompensating strabismus like accommodative
      esotropia, pathophoria, strabismus surso- and deorsoadductorius, retraction
      syndrome, Brown's syndrome and esotropia in high myopia only need ophthalmologic
      treatment. Orbital injury, orbital tumor, ocular myositis, Graves orbitopathy and
      vascular disease usually require multidisciplinary management. Neurogenic
      paresis, superior oblique myokymia, ocular neuromyotonia, myasthenia, chronic
      progressive external ophthalmoplegia (CPEO), internuclear ophthalmoplegia (INO)
      and skew deviation require specific neurologic examination. Treatment of diplopia
      includes treatment of the fundamental disorder, monocular occlusion, prisms and
      strabismus surgery.

PMID- 22986080
TI  - [How to deal with orbital syndrome: diagnostic approach].
AB  - Evaluation of a patient with orbital disease needs a multidisciplinary approach.
      Clinical examination should seek to glean information regarding pathophysiologic
      effect and location and to evaluate consequences of this disease on cosmetic,
      vision and ocular motility. Procedures of imaging are based on the implied
      complementary exams that should be done according to the suspected clinical
      location and characters help to characterize the underlying process. Imaging can
      define the location, size, limits and relationship of the disease to other
      tissues and especially to the vascular system. It may be completed by blood test.
      The final diagnosis is based on several arguments and can appeal for a diagnostic
      biopsy in the most difficult cases.

PMID- 22986081
TI  - Psoriatic patients with diabetes are prone to develop digestive organ cancers: a
      population-based study in Taiwan.
AB  - BACKGROUND: Psoriasis is an inflammatory skin condition. Epidemiology studies
      from different parts of the world have shown that psoriasis is associated with
      different components of metabolic syndrome. The association between psoriasis and
      development of cancer has not yet been clearly established. OBJECTIVE: We
      hypothesize that chronic inflammation is the driving force that enhances the risk
      of malignancy in psoriatic patients and suspect that psoriatic patients have
      higher risks for developing cancers that are most prevalent in the studied
      population. METHODS: Using the nested case-control approach derived from the
      Taiwanese population-based cohort, the current study was launched to validate
      this hypothesis. Results 8180 psoriatic patients and 163,600 age-matched controls
      were included in this study. Psoriatic patients were 1.20 folds (95% CI=1.06
      1.36; p=0.004) more likely than controls to develop cancer. Further analyses
      revealed that incident cancers derived from digestive tract, the most common
      cancer origin found in Taiwanese population, were most significantly associated
      psoriasis. Patients with psoriasis and diabetes mellitus, a frequent comorbid
      condition independently associate with both psoriasis and cancer, conferred the
      highest risk for developing digestive tract cancers, having risks of 1.98 folds
      (95% CI: 1.11-3.52) and 1.68 folds (95%CI: 1.23-2.28) for the 41-60 years-old and
      61-80 years-old age group, respectively. Both psoriasis and diabetes were
      independently associated with development of digestive tract cancers in the 41-60
      years-old patient group. CONCLUSION: Prevalent cancers in the population should
      be carefully monitored in the psoriatic patients after middle age (beyond 40
      years of age) especially for those with concomitant diabetic conditions.

PMID- 22986082
TI  - Sustained release from hot-melt extruded matrices based on ethylene vinyl acetate
      and polyethylene oxide.
AB  - The aim of the present study was to evaluate the importance of matrix flexibility
      of hot-melt extruded (HME) ethylene vinyl acetate (EVA) matrices (with vinyl
      acetate (VA) contents of 9%, 15%, 28% and 40%), through the addition of
      hydrophilic polymers with distinct swelling capacity. Polyethylene oxide (PEO
      100K, 1M and 7M) was used as swelling agent and metoprolol tartrate (MPT) as
      model drug. The processability via HME and drug release profiles of EVA/MPT/PEO
      formulations were assessed. Solid state characteristics, porosity and polymer
      miscibility of EVA/PEO matrices were evaluated by means of DSC, X-ray tomography
      and Raman spectroscopy. The processability via HME varied according to the VA
      content: EVA 40 and 28 were extruded at 90 degrees C, whereas higher viscosity
      EVA grades (EVA 15 and 9) required a minimum extrusion temperature of 110 degrees
      C to obtain high-quality extrudates. Drug release from EVA matrices depended on
      the VA content, PEO molecular weight and PEO content, matrix porosity as well as
      pore size distribution. Interestingly, the interplay of PEO leaching, matrix
      swelling, water influx and changes in matrix porosity influenced drug release:
      EVA 40- and 28-based matrices extruded with PEO of higher MW accelerated drug
      release, whereas for EVA 15- and 9-based matrices, drug release slowed down.
      These differences were related to the distinct polymer flexibility imposed by the
      VA content (lower VA content presents higher crystallinity and less free movement
      of the amorphous segments resulting in a higher rigidity). In all cases,
      diffusional mass transport seems to play a major role, as demonstrated by
      mathematical modeling using an analytical solution of Fick's second law. The
      bioavailability of EVA 40 and 28 matrices in dogs was not significantly
      different, independent of PEO 7M concentration.

PMID- 22986083
TI  - Arbutus menziesii (Ericaceae) facilitates regeneration dynamics in mixed
      evergreen forests by promoting mycorrhizal fungal diversity and host
      connectivity.
AB  - PREMISE OF STUDY: In the mixed evergreen forests in the western United States,
      Arbutus menziesii is able to quickly resprout following disturbance and, as such,
      act as a nurse tree during forest regeneration. The mechanism for this nurse tree
      effect has frequently been ascribed to mycorrhizal fungi, but no detailed
      molecular-based studies of the mycorrhizal fungal communities associated with A.
      menziesii roots have yet been conducted. * METHODS: We examined the structure of
      the mycorrhizal fungal communities associated with A. menziesii in varying forest
      types and seasons and assessed the potential for common mycelial networks between
      A. menziesii and Pinaceae hosts, particularly Pseudotsuga menziesii. Study sites
      were located in the Klamath-Siskyou region in southern Oregon, United States.
      Molecular approaches were used to identify the mycorrhizal fungi (ITS rDNA) and
      plant hosts (trnL cDNA). * KEY RESULTS: Arbutus menziesii hosts a highly diverse
      mycorrhizal fungal community with similar composition to communities found on
      other angiosperm and Pinaceae hosts. Phylogenetic analyses of the mycorrhizal
      genus Piloderma revealed that host species and geographic location had little
      effect on fungal taxon relatedness. Multihost fungal taxa were significantly more
      frequent and abundant than single-host fungal taxa, and there was high potential
      for the formation of common mycelial networks with P. menziesii. * CONCLUSIONS:
      Our results suggest A. menziesii is a major hub of mycorrhizal fungal diversity
      and connectivity in mixed evergreen forests and plays an important role in forest
      regeneration by enhancing belowground resilience to disturbance.

PMID- 22986084
TI  - Microsatellite markers for Plathymenia reticulata (Leguminosae)1.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed and characterized to
      investigate genetic diversity and gene flow and to help in conservation efforts
      for the endangered timber species Plathymenia reticulata. * METHODS AND RESULTS:
      Eleven microsatellite loci were characterized using 60 adult trees of two
      populations of P. reticulata from the Atlantic Forest of southern Bahia, Brazil.
      Of these, nine loci were polymorphic, with an average of 4.39 alleles per locus.
      The average expected heterozygosity per population ranged from 0.47 to 0.55. The
      combined exclusion probability was 0.99996. * CONCLUSIONS: Our results reveal
      that the microsatellite markers developed in this study are an effective tool for
      paternity and genetic structure analysis that may be useful for conservation
      strategies.

PMID- 22986085
TI  - Viral fitness: definitions, measurement, and current insights.
AB  - Viral fitness is an active area of research, with recent work involving an
      expanded number of human, non-human vertebrate, invertebrate, plant, and
      bacterial viruses. Many publications deal with RNA viruses associated with major
      disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study
      topics include drug resistance, immune escape, viral emergence, host jumps,
      mutation effects, quasispecies diversity, and mathematical models of viral
      fitness. Important recent trends include increasing use of in vivo systems to
      assess vertebrate virus fitness, and a broadening of research beyond replicative
      fitness to also investigate transmission fitness and epidemiologic fitness. This
      is essential for a more integrated understanding of overall viral fitness, with
      implications for disease management in the future.

PMID- 22986087
TI  - Green tea and green tea catechin extracts: an overview of the clinical evidence.
AB  - BACKGROUND: Tea leaves contain varying amounts of polyphenols of which the
      majority are catechins. There has been a sizable amount of research on the
      potential effect of green tea catechins for cancer risk, cardiovascular disease
      risk and weight loss; all conditions that are relevant to mid-life health. The
      aim was to produce an overview of the evidence for green tea for these three
      important health conditions. METHODS: The databases Medline (& Medline in
      process) and Embase, were searched for systematic reviews and meta-analyses using
      customised search strategies performed up until April 2012. Assessment of
      Multiple Systematic Reviews criteria were used to assess the quality of the
      included reviews. Relevant data were extracted into predefined tables. The
      results are described and discussed narratively. RESULTS: We included eight
      systematic reviews and meta-analyses covering the topics of cancer risk (n=2),
      cardiovascular risk (n=4) and weight loss (n=2). CONCLUSIONS: The evidence for
      green tea and cancer risk is inadequate and inconclusive. However there is some
      positive evidence for risk reduction of breast, prostate, ovarian and endometrial
      cancers with green tea. RCTs of green tea and cardiovascular risk factors suggest
      that green tea may reduce low-density lipoproteins and total cholesterol,
      although studies are of short duration. There is no robust evidence to support a
      reduction in coronary artery disease risk in green tea drinkers. There are a
      considerable number of RCTs to suggest that green tea does reduce body weight in
      the short term, but this not likely to be of clinical relevance.

PMID- 22986088
TI  - Measures of combined antioxidant and pro-oxidant exposures and risk of overall
      and advanced stage prostate cancer.
AB  - PURPOSE: Oxidative stress is possibly related to prostate carcinogenesis. We
      constructed a dietary antioxidant score, which is a measure of combined
      antioxidant exposures, and an oxidative balance score (OBS), which is a measure
      of combined antioxidant and pro-oxidant exposures. We hypothesized that both
      scores are inversely associated with the risk of prostate cancer (PCa). METHODS:
      We conducted a case-cohort study among 58,279 men in the Netherlands Cohort
      Study. Cohort members completed a baseline questionnaire. From 1986 to 2003, 3451
      patients with PCa were identified including 1196 advanced cancers (stage III/IV).
      The antioxidant score and the OBS were created by summing quartile and category
      scores of individual score constituents, which had an equal weight. Pro-oxidants
      were scored in the opposite way to antioxidants. RESULTS: Both the antioxidant
      score and OBS were not associated with risk of overall PCa or PCa subgroups on
      the basis of disease stage. Most score constituents were not associated with the
      risk of PCa. Total catechin intake was associated with a decreased risk of stage
      IV PCa (greatest vs. lowest quartile: hazard ratio, 0.76; 95% confidence
      interval, 0.59-0.98). CONCLUSIONS: The antioxidant score and OBS were not
      associated with risk of overall and advanced-stage PCa.

PMID- 22986086
TI  - Non-stationarity and power spectral shifts in EMG activity reflect motor unit
      recruitment in rat diaphragm muscle.
AB  - We hypothesized that a shift in diaphragm muscle (DIAm) EMG power spectral
      density (PSD) to higher frequencies reflects recruitment of more fatigable fast
      twitch motor units and motor unit recruitment is reflected by EMG non
      stationarity. DIAm EMG was recorded in anesthetized rats during eupnea, hypoxia
      hypercapnia (10% O(2)-5% CO(2)), airway occlusion, and sneezing (maximal DIAm
      force). Although power in all frequency bands increased progressively across
      motor behaviors, PSD centroid frequency increased only during sneezing (p<0.05).
      The non-stationary period at the onset of EMG activity ranged from ~80 ms during
      airway occlusion to ~150 ms during eupnea. Within the initial non-stationary
      period of EMG activity 80-95% of motor units were recruited during different
      motor behaviors. Motor units augmented their discharge frequencies progressively
      beyond the non-stationary period; yet, EMG signal became stationary. In
      conclusion, non-stationarity of DIAm EMG reflects the period of motor unit
      recruitment, while a shift in the PSD towards higher frequencies reflects
      recruitment of more fatigable fast-twitch motor units.

PMID- 22986089
TI  - Effects of Thai Musa species on prevention of UVB-induced skin damage in mice.
AB  - The effects of oral administration of Musa sapientum and Musa suerier on
      prevention of UVB induced skin damages were investigated in male ICR mice.
      Animals were orally administered 50mg/day ascorbic acid, or M. sapientum or M.
      suerier's fruit pulps at dose of 0.5, 1 or 1.5 mg/g body weight/day for 12 weeks.
      Concurrently, the shaved backs of animals were irradiated with UVB for 12weeks.
      The intensity of irradiation was progressively increased, from 54 mJ/cm(2) per
      exposure at week 1-126 mJ/cm(2) at week 11. A significant decrease (p<0.05) in
      skin elasticity (from 0.82+/-0.02 to 0.42+/-0.09) and total glutathione (from
      (193.6+/-18.7 to 152.7+/-7.8 ng/mg protein) as compared with the control group
      (water-administered UVB-irradiated mice) was observed after 12 weeks of UVB
      exposure. When L-ascorbic acid (0.72+/-0.01) or 1mg/g body weight/day M. suerier
      (0.84+/-0.06) were administered to UVB-irradiated mice, the reduction in skin
      elasticity was significantly inhibited (p<0.05). Moreover, the significant
      increase (p<0.05) in level of total glutathione was found in these groups
      (220.8+/-13.3 ng/mg protein for l-ascorbic acid and 224.9+/-20.1 ng/mg protein
      for M. suerier). These findings suggest the potential effect of daily consumption
      of M. suerier on prevention of skin damage from repeated UVB exposure.

PMID- 22986090
TI  - Morphological and immunohistochemical characterisation of seminomas in Norwegian
      dogs.
AB  - BACKGROUND: Seminomas in the dog have traditionally been assumed to resemble
      human spermatocytic seminomas, based on their low malignancy and high occurrence
      in old individuals. However, recently published studies indicate that canine
      seminomas can be classified as classical and spermatocytic seminomas in a similar
      way as in man, and that classical seminomas comprise a substantial proportion of
      seminomas in the dog. These two factors both contribute to increasing the
      potential of canine seminoma as a relevant model for human testicular cancer. The
      aim of the present study was to characterise seminoma in Norwegian dogs using
      morphology and immunohistochemistry, and determine whether these tumours are
      comparable with human classical seminoma. METHODS: By applying diagnostic
      criteria from human pathology, 45 seminomas from the Norwegian Canine Cancer
      Register were examined histologically with hematoxylin and eosin (HE) and
      periodic acid-Schiff (PAS) stains. All sections were stained
      immunohistochemically with antibodies against human placental alkaline
      phosphatase (PLAP) and the transmembrane receptor c-KIT. RESULTS: Although two of
      the seminomas showed immunohistochemical staining characteristics indicative of
      classical seminoma (PLAP+/c-KIT+), all 45 examined seminomas were morphologically
      consistent with spermatocytic seminoma. CONCLUSIONS: The value of canine seminoma
      as a model for SE in man remains unclear. Among the 45 investigated tumours from
      Norwegian dogs, none were classified as classical seminoma based on morphological
      criteria consistent with human seminomas. Regional or breed differences in the
      occurrence of classical seminoma in the dog, as well as the lack of uniform
      diagnostic criteria, might explain the discrepancy between the findings in the
      current study and the results presented by other authors.

PMID- 22986091
TI  - Effects of ambient and elevated level of ozone on Brassica campestris L. with
      special reference to yield and oil quality parameters.
AB  - Tropospheric ozone (O(3)) has become a serious threat to growth and yield of
      important agricultural crops over Asian regions including India. Effect of
      elevated O(3) (ambient+10ppb) was studied on Brassica campestris L. (cv. Sanjukta
      and Vardan) in open top chambers under natural field conditions. Eight hourly
      mean ambient O(3) concentration varied from 26.3ppb to 69.5ppb during the growth
      period. Plants under O(3) exposure showed reductions in photosynthetic rate,
      reproductive parameters, yield as well as seed and oil quality. Cultivar Sanjukta
      showed more reduction in photosynthetic characteristics, reproductive structures
      and seed and oil quality. However, total yield was more affected in Vardan.
      Exposure of O(3) increased the degree of unsaturation and level of PUFA, omega
      6fatty acid, linolenic acid and erucic acid in oil indicating the deterioration
      of its quality. The study further confirmed that there is a correspondence
      between O(3) induced change in photosynthetic processes, reproductive development
      and yield and did not find any compensatory response in the final yield.

PMID- 22986092
TI  - First-time comparison of the in vitro antimalarial activity of Artemisia annua
      herbal tea and artemisinin.
AB  - Artemisia annua tea has been proven to be a very effective treatment for malaria
      in various clinical trials, but to date its efficacy has not been investigated in
      vitro. A study was therefore performed to evaluate the effects of A. annua tea on
      Plasmodium falciparum cultures in vitro. The concentration of artemisinin in the
      herbal tea preparation was also determined. The herbal tea extract was tested
      against chloroquine (CQ)-sensitive D10 and CQ-resistant W2 strains of P.
      falciparum using the parasite lactate dehydrogenase assay. Quantification of
      artemisinin in the extract of leaves of A. annua was performed using proton
      nuclear magnetic resonance ((1)H-NMR). Results of the in vitro tests were
      consistent with the clinical efficacy of A. annua tea [50% inhibitory
      concentration (IC(50)) for strain D10=1.11+/-0.21 MUg/ml; IC(50) for strain
      W2=0.88+/-0.35 MUg/ml]. The concentration of artemisinin in A. annua tea (0.18+/
      0.02% of dry weight) was far too low to be responsible for the antimalarial
      activity. The artemisinin present in the tea is probably co-solubilised with
      other ingredients, some of which also have antimalarial activity and act
      synergistically with it. These compounds also merit further research to determine
      whether their presence hinders the development of parasite resistance compared
      with pure artemisinin.

PMID- 22986093
TI  - Characteristics of informal caregivers of patients with dementia in Alicante
      province.
AB  - INTRODUCTION: Informal caregivers provide care to dementia patients, and this
      service prolongs their stay at home. OBJECTIVES: To describe characteristics of
      dementia patients in the province of Alicante, as well as the profiles and roles
      of caregivers who assist them. PATIENTS AND METHODS: Multi-centre prospective
      study carried out in 4 neurology departments in Alicante (June 2009 to January
      2010). Dementia patients' relatives/caregivers were included in sequential order.
      The following variables were analysed: a) Demographic information pertaining to
      the patient and caregivers (age, sex, marital and employment status, educational
      level, relationship to patient); b) patient's family unit; c) motivating factor
      for primary caregiver (PC); d) secondary caregiver (SC) roles; e) country of
      citizenship of formal caregiver (FC) and source of remuneration (private/public);
      f) caregivers' knowledge of dementia. RESULTS: Most of our patients live at home
      (74.8%), and are female (69%) with Alzheimer's disease (78.4%) in a moderately
      severe stage (GDS level 4-5, 71.6%). PCs and SCs are mainly women (72.1% and
      60.5% respectively), middle-aged and directly related to the patient
      (sons/daughters account for 64.3% of the PCs and 54.4% of the SCs); most are
      homemakers with a low educational level. Caregivers in the first category (PC)
      provide care due to moral obligation (75%), while those in the second (SC)
      involve patients in leisure or other stimulating activities (82.3%). Absent
      caregivers tend to be males (73.3%) residing long distances from the relative
      (52.4%). The FC tends to be female (91.7%), Spanish (81.8%) and privately
      remunerated. CONCLUSIONS: Women dominate the network of caregivers for dementia
      patients, whether as principal caregivers, supporting caregivers or formal
      caregivers (in all cases, they have only limited training in dementia
      management). Males are largely absent. Better knowledge of the care structure
      supporting dementia patients may be helpful in the overall management of these
      patients.

PMID- 22986094
TI  - A comparison of surgical outcomes between laparoscopic and open myomectomy in
      Southern Taiwan.
AB  - OBJECTIVE: To compare operative data and operative and clinical outcomes of
      laparoscopic myomectomy (LM) with those of open myomectomy (OM). METHODS: In a
      retrospective study, the records of 81 women who underwent LM and 74 women who
      underwent at E-DA Hospital, Yan-Chau Shiang, Taiwan, from June 2004 to October
      2007 were reviewed. Patient demographic, intraoperative, and postoperative data
      were compared between the 2 surgical groups. RESULTS: The mean +/- SD age of
      patients in the OM and LM groups was 40.08 +/- 6.49 years and 41.14 +/- 6.46
      years, respectively. Median (range) surgical time and blood loss were both
      significantly less in the LM group than in the OM group (100 min [73-120 min]
      versus 120 min [90-146 min], and 100mL [100-200 mL] versus 150 mL [100-305 mL],
      respectively). Thirteen patients in the OM group required a blood transfusion,
      compared with 1 in the LM group. There was no difference in complications or
      recurrences between the 2 groups. CONCLUSION: Compared with OM, LM was found to
      be associated with shorter surgical time and less blood loss, but there was no
      difference in the rate of complications or recurrence between the 2 groups.

PMID- 22986095
TI  - Outcomes of traditional prolapse surgery for pelvic organ prolapse repair at a
      single center.
AB  - OBJECTIVE: To evaluate the clinical outcomes of traditional surgical approaches
      to pelvic organ prolapse. METHODS: From January 20, 2000, to March 24, 2009, 182
      patients underwent traditional prolapse surgery at Osaka City University Graduate
      School of Medicine, Osaka, Japan, after prolapse assessment by the pelvic organ
      prolapse quantification system. Incontinence, defined as more than 2 g of urine
      leaked in a 1-hour pad test; posterior urethrovesical angle, using chain
      cystography; and quality of life (QOL), using a face visual analog scale, were
      assessed 1, 3, 6, and 12 months postoperatively, and then annually for 2 more
      years, in the 167 patients who completed follow-up. The presence of lower urinary
      tract symptoms was determined preoperatively and postoperatively. RESULTS: The
      anatomic and subjective recurrence rates were 21.0% and 6.0%. There was a
      significant difference in time to recurrence between anatomic and subjective
      prolapse. The posterior urethrovesical angle was improved postoperatively. The
      prevalence of lower urinary tract symptoms was 67.1% preoperatively and decreased
      to 28.2%, 17.2%, 16.2%, 15.6%, and 15.6% at 1 month, 6 months, 1 year, 2 years,
      and 3 years, respectively, and QOL was improved postoperatively regardless of
      anatomic recurrence. CONCLUSION: Anatomic support and QOL were satisfactory after
      traditional prolapse surgery.

PMID- 22986096
TI  - Syncytiotrophoblast-derived microparticle shedding in early-onset and late-onset
      severe pre-eclampsia.
AB  - OBJECTIVE: To determine the concentration of syncytiotrophoblast-derived
      microparticles (STBMs) in the maternal circulation and the rate of
      syncytiotrophoblast apoptosis in the placenta of patients with early-onset and
      late-onset severe pre-eclampsia. METHODS: A prospective case-control study was
      conducted that enrolled 15 women with early-onset severe pre-eclampsia, 15 women
      with late-onset severe pre-eclampsia, and 10 women with normal pregnancies.
      Plasma STBM levels were measured by enzyme-linked immunosorbent assay, while
      placental levels of active caspase-3 were determined by western blotting. Human
      umbilical vein endothelial cells (HUVECs) were cultured with STBMs and the
      proliferation and apoptosis rates of the HUVECs assessed. RESULTS: Levels of
      STBMs in the early-onset group (71.2 +/- 20.7 ng/mL) were significantly higher
      than those detected in the late-onset group (41.9 +/- 29.7 ng/mL) and the control
      group (26.3 +/- 11.2 ng/mL) (P<0.05). The amount of active caspase-3 was
      increased in the early-onset (0.85 +/- 0.61) and late-onset groups (0.77 +/-
      0.46) relative to the control group (0.32 +/- 0.15) (P<0.05). Proliferation of
      HUVECs was inhibited, while apoptosis was elevated, following co-culture with
      STBMs. CONCLUSION: Shedding of STBMs into the maternal circulation occurs in
      greater amounts in early-onset pre-eclampsia than in late-onset pre-eclampsia.

PMID- 22986097
TI  - Morbidity and pregnancy outcomes associated with sickle cell anemia among Saudi
      women.
AB  - OBJECTIVE: To identify morbidity and pregnancy outcomes associated with sickle
      cell disease (SCD) among pregnant Saudi women. METHODS: A 10-year retrospective
      study was conducted at King Khalid University Hospital in Riyadh, Saudi Arabia,
      that included 392 cases of SCD in pregnancy and 784 controls with normal
      hemoglobin phenotype, who were selected and matched for age, parity, and delivery
      outcome. The main outcome measures were morbidity, maternal outcomes, and fetal
      outcomes. RESULTS: The incidence of SCD was 1.1% among all deliveries, with 2
      maternal deaths (0.5%) and a perinatal mortality rate of 77.7 per 1000
      deliveries. The major maternal complications in the SCD group were anemia
      (86.2%); sickle cell crisis (64.8% overall, with 43.1% vaso-occlusive, 21.2%
      hemolytic, and 0.5% sequestration or aplastic); bacterial infection (8.8%);
      preterm delivery (15.3%); and pre-eclampsia (9.7%). Fetal growth restriction and
      stillbirths accounted for 65.6% of the perinatal mortality. Blood transfusion was
      indicated in 33.7% of pregnancies in the SCD group. CONCLUSION: Pregnant Saudi
      women with SCD are at increased risk for pregnancy-related complications, as well
      as fetal morbidity and mortality. A critical need exists among Saudi hospitals
      for a multidisciplinary approach to the management of pregnancies complicated by
      SCD.

PMID- 22986098
TI  - Prevalence of high-risk HPV and associated risk factors in cases of cervical
      carcinoma in Tamil Nadu, India.
AB  - OBJECTIVE: To assess the prevalence of HPV infection among women with cervical
      cancer in Tiruchirapalli, Tamil Nadu, India. METHODS: A case-control study was
      conducted with 246 women with cervical cancer and 257 control participants aged
      between 20 and 70 years. The presence of HPV DNA was determined using the MY09/11
      PCR protocol, the GP5(+)/6(+) PCR protocol, and type-specific PCR-based assays.
      RESULTS: The overall HPV prevalence was 54.9% and HPV 16 was the most prevalent
      type. The women the most vulnerable for HPV infection were those aged 41 to 60
      years. The major contributing risk factors for cervical cancer were having had 3
      or more pregnancies (OR 19.2; 95% CI, 10.78-10.16); harboring high-risk HPV DNA
      (OR 15.3; 95% CI, 9.81-23.8); being a manual worker (OR 14.9; 95% CI, 9.62
      23.08); being illiterate (OR 8.28; 95% CI, 5.51-12.43); and having never been
      screened for cervical dysplasia (OR 6.70; 95% CI, 10.78-34.44). CONCLUSION: The
      present report on the overall and type-specific prevalence rates and risk burden
      of HPV infection in Tamil Nadu confirms that screening and vaccination programs
      are urgently needed in this state to overcome the burden of HPV-associated
      cervical cancer.

PMID- 22986100
TI  - Wintergreen oil: a novel method in Wheatley's trichrome staining technique.
AB  - Permanent staining of faecal smears by Wheatley's trichrome technique has been
      used by many scientists for the detection of parasites in the past and it was
      found to be highly sensitive. This study was conducted to evaluate the use of
      Wintergreen oil in comparison with xylene in Wheatley's trichrome staining
      technique, as the reference technique. In a blind comparison study, 500 collected
      faecal samples from aboriginal communities were examined. Wintergreen oil was
      found to be more superior than xylene as a clearing agent in the Wheatley's
      trichrome staining of polyvinyl alcohol-fixed faecal smears for the
      identification of intestinal protozoa. Elimination of toxic, carcinogenic, and
      fire hazards makes Wintergreen oil the preferred choice in routine parasitology
      examinations.

PMID- 22986099
TI  - Peripheral modulation of smell: fact or fiction?
AB  - Despite studies dating back 30 or more years showing modulation of odorant
      responses at the level of the olfactory epithelium, most descriptions of the
      olfactory system infer that odorant signals make their way from detection by
      cilia on olfactory sensory neurons to the olfactory bulb unaltered. Recent
      identification of multiple subtypes of microvillar cells and identification of
      neuropeptide and neurotransmitter expression in the olfactory mucosa add to the
      growing body of literature for peripheral modulation in the sense of smell.
      Complex mechanisms including perireceptor events, modulation of sniff rates, and
      changes in the properties of sensory neurons match the sensitivity of olfactory
      sensory neurons to the external odorant environment, internal nutritional status,
      reproductive status, and levels of arousal or stress. By furthering our
      understanding of the players mediating peripheral olfaction, we may open the door
      to novel approaches for modulating the sense of smell in both health and disease.

PMID- 22986101
TI  - Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in
      mantle cell lymphoma.
AB  - Overexpression of the cellular nuclear exportin 1, more commonly called
      chromosomal region maintenance 1 (CRM1), has been associated with malignant
      progression and mortality. Therefore, activation of nuclear export can play a
      significant etiologic role in some forms of human neoplasia and serve as a novel
      target for the treatment of these cancers. Mantle cell lymphoma (MCL) is an
      aggressive histotype of B-cell non-Hodgkin lymphoma that remains incurable. The
      objective of this study was to investigate the functional significance of CRM1 in
      MCL by evaluating the therapeutic efficacy of CRM1 inhibition in MCL in vitro and
      in vivo. Our results showed that CRM1 is highly expressed in MCL cells and is
      involved in regulating growth and survival mechanisms through the critical
      nuclear factor-kappaB survival pathway, which is independent of p53 status.
      Inhibition of CRM1 by two novel selective inhibitors of nuclear export (SINE),
      KPT-185 and KPT-276, in MCL cells resulted in significant growth inhibition and
      apoptosis induction. KPT-185 also induced CRM1 accumulation in the nucleus,
      resulting in CRM1 degradation by the proteasome. Oral administration of KPT-276
      significantly suppressed tumor growth in an MCL-bearing severe combined
      immunodeficient mouse model, without severe toxicity. Our data suggest that SINE
      CRM1 antagonists are a potential novel therapy for patients with MCL, particular
      in relapsed/refractory disease.

PMID- 22986102
TI  - Cylindrospermopsin: water-linked potential threat to human health in Europe.
AB  - Cylindrospermopsin (CYN) is a secondary metabolite produced by several
      cyanobacteria species. Its potential effect on human health includes liver,
      kidneys, lungs, spleen and intestine injuries. CYN can be cyto- and genotoxic to
      a variety of cell types. Occurrence and expansion of species able to synthesize
      CYN in European water bodies has been recently reported and raised awareness of
      potential harm to human health. Therefore, surface water of different human use
      should be monitored for the presence of toxic species of blue-green algae. This
      paper aims to describe the distribution of CYN producers in Europe and the
      potential effects of the toxin on human health according to the current state of
      knowledge.

PMID- 22986103
TI  - Responses of laboratory exposed catfish (Clarias gariepinus) to environmentally
      relevant concentrations of p,p'-DDT.
AB  - Technical grade DDT is annually sprayed for malaria control in many under
      developed countries world wide. Despite the controversy surrounding the use of
      DDT, minimal research concerning the effects on indigenous fish species in these
      areas has been conducted. In this study, the objectives were to identify some of
      the effects of sprayed p,p'-DDT on the common African sharptooth catfish species
      (Clarias gariepinus) under laboratory conditions. The effects were assessed by
      exposing specimens to three environmentally relevant concentrations of p,p'-DDT
      (0.66, 1.36 and 2.72 MUg/l) for 21 days and analysing a suite of biomarkers in
      the plasma, gonads and body morphometrics. The biomarkers were specifically
      selected based on their practicality in developing countries, which could
      potentially be utilised for continued monitoring, and included alkali-labile
      phosphate (ALP), calcium, magnesium and zinc as the indirect measures of
      vitellogenin, gonadosomatic index, gonad mass manipulated using analysis of
      covariance, and condition factor. The results showed no significant (p<0.05) dose
      dependent changes in the plasma, gonads and body condition of C. gariepinus,
      indicating that these species were not responsive to the p,p'-DDT concentrations
      when exposed sub-chronically. This lack of a response suggested that mature C.
      gariepinus are tolerant to 21 days exposure of low levels of p,p'-DDT.

PMID- 22986104
TI  - Effects of C-Phycocyanin on the representative genes of tumor development in
      mouse skin exposed to 12-O-tetradecanoyl-phorbol-13-acetate.
AB  - C-Phycocyanin (C-PC), a biliprotein from the sea weed, has been shown to have the
      beneficial effects like antioxidant, anti-inflammatory, neuroprotective, and
      hepatoprotective properties and is used as food supplement. We are showing the
      effect of C-Phycocyanin on the early events altered by tumor promoter. TPA
      induced the expression of critical events of tumorigenesis like ornithine
      decarboxylase, cyclooxygenase-2, interleukin-6 and pSTAT3 in mouse skin after 5h
      of application, whereas expression of transglutaminase2 was decreased at this
      time point. This TPA-caused altered expression of genes was prevented in presence
      of C-Phycocyanin. This prevention by C-Phycocyanin appeared to be dependent on
      the dose of C-Phycocyanin used. The results are useful for the detailed study on
      the preventive effect of C-Phycocyanin on TPA induced tumor promotion.

PMID- 22986105
TI  - Ameliorative effect of silibinin against N-nitrosodimethylamine-induced hepatic
      fibrosis in rats.
AB  - The protective effect of silibinin (SBN) against hepatic fibrosis induced by
      repeated intermittent administration of N-nitrosodimethylamine (DMN) was
      investigated in rats. Oral administration of SBN recovered body and liver weight
      loss and reversed the elevation of serum AST, ALT and ALP accompanied by their
      fall in the liver tissue in DMN-induced fibrotic rats. Severe oxidative stress
      induced in fibrotic rats was evidenced by two to three fold elevation in MDA and
      protein carbonyl levels associated with a fall in the activities of SOD and CAT
      in repeated DMN treatment and this adversity was protected by SBN post-treatment.
      Further, the fall in the activities of ATPases and increase in the levels of
      hydroxyproline and collagen observed in the liver tissue of DMN treated rats was
      prevented and reversed back toward normalcy by SBN post-treatment. Recovery of
      rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory
      changes and hepatic fibrosis by SBN treatment is also confirmed by both H & E and
      Masson's trichrome stained histopathological evaluation of liver tissue. In
      conclusion, SBN exhibit hepatoprotective, antioxidant, free radical scavenging,
      membrane stabilizing and anti-fibrotic activity against DMN-induced hepatic
      fibrosis suggesting that it may be useful as a therapeutic agent toward
      amelioration of hepatic fibrosis.

PMID- 22986106
TI  - Di-(2-ethylhcxyl) phthalate reduces progesterone levels and induces apoptosis of
      ovarian granulosa cell in adult female ICR mice.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) as an environmental endocrine disruptor is a
      known reproductive toxicant and carcinogen. The purpose of this study was to
      evaluate the female reproductive toxicity of DEHP. Sixty ICR female mice were
      randomized into four groups dosed with 0, 125, 500, or 2 000 mg/kg DEHP by gavage
      for 16 weeks, 6 days/week. DEHP treatment prolonged duration of the estrous cycle
      in mice at 500 and 2000 mg/kg DEHP, but no significant effects on estrus phase of
      the cycle in each group were detected. Exposure to DEHP inhibited secretion of
      serum progesterone. DEHP arrested granulosa cells at G(0)/G(1) phases and
      increased proportion of apoptosis cells at 500 and 2000 mg/kg DEHP. There was no
      significant difference in P450arom mRNA expression among groups. Results
      demonstrate that DEHP can produce toxicity in female reproductive system.

PMID- 22986107
TI  - Rethinking the (im)possible in evolution.
AB  - This paper will discuss the philosophical background to evolutionary theory and
      present multiple counterfactuals to each of the following seven empirically
      unsustainable but nonetheless widespread assumptions about genomic (DNA-based)
      evolution: 1. "All heredity transmission occurs from parent to progeny" 2.
      "Mutations are the result of inevitable replication errors" 3. "Mutations occur
      at constant low probabilities over time" (= there are "mutation rates") 4. "Virus
      infection cannot induce genetic changes giving heritable resistance" 5.
      "Mutations cannot be targeted within the genome" 6. "Spontaneous hereditary
      changes are localized and limited to those of small effect" 7. "Cells cannot
      integrate DNA change with biologically useful adaptive needs". The summary take
      home lesson is that we have to change from thinking of the genome as a read-only
      memory (ROM) that dictates the fate of the cell or organism to conceptualizing
      the genome as a read-write (RW) organelle modified transiently or permanently by
      the cell at different time scales.

PMID- 22986108
TI  - A 1 Mb de novo deletion within 11q13.1q13.2 in a boy with mild intellectual
      disability and minor dysmorphic features.
AB  - We report a 11 year old male patient ascertained for mild intellectual disability
      and minor dysmorphic features, carrying a 1 Mb de novo deletion on chromosome
      11q13.1q13.2 detected by aCGH. This is the first report of a deletion in this
      region in a patient presenting with intellectual impairment and mild dysmorphic
      traits. The 1 Mb deleted area encompasses 47 RefSeq genes, including Cornichon
      homologue 2 (CNIH2), Cofilin-1 (CFL1) and neuronal PAS domain-containing protein
      4 (NPAS4), which are highly expressed in the central nervous system. Knockout of
      the CNIH2 and CFL1 orthologues in animals results in migration disturbances,
      while low or no expression of Npas4 in mice results in impairment of memory and
      learning. These three genes have previously been suggested as candidate genes for
      neurological disorders.

PMID- 22986109
TI  - Clinical evidence of sustained chronic inflammatory reaction in retinitis
      pigmentosa.
AB  - PURPOSE: To study the nature of inflammatory reaction in eyes of patients with
      retinitis pigmentosa (RP) and its possible role in the pathogenesis of RP.
      DESIGN: Retrospective, observational study. PARTICIPANTS AND CONTROLS: Three
      hundred seventy-one consecutive patients diagnosed with typical RP were included
      in this study. We included 165 patients without active inflammatory diseases,
      including 20 patients diagnosed with cataract, and 36 patients diagnosed with
      idiopathic epiretinal membrane as controls. METHODS: Density of the inflammatory
      cells in the anterior vitreous cavity was measured and graded by slit-lamp
      biomicroscopy. A multiplex enzyme-linked immunosorbent assay (ELISA) was
      performed to evaluate the concentration of cytokines and chemokines in aqueous
      humor and vitreous fluid of patients with RP and controls. In addition, we
      investigated the relationship between visual function and anterior vitreous cells
      in these patients. MAIN OUTCOME MEASURES: Slit-lamp biomicroscopic analysis, best
      corrected visual acuity, visual field analysis, and multiplex ELISA. RESULTS: In
      190 of 509 eyes with RP (37.3%), "1+" (5-9 cells per field) or more cells were
      observed in the anterior vitreous cavity. Strong inflammatory reaction with "2+"
      cells (10-30 cells per field) was associated with younger age. In the elderly
      patients with RP, significantly decreased visual function was seen in a group
      with "1+" or more cells (P<0.05). Moreover, the levels of a variety of
      proinflammatory cytokines and chemokines, including monocyte chemotactic protein
      1, were increased both in the aqueous humor and vitreous fluid of RP patients
      compared with the levels in control patients. CONCLUSIONS: Sustained chronic
      inflammatory reaction may underlie the pathogenesis of RP, suggesting
      interventions for ocular inflammatory reaction as a potential treatment for
      patients with RP. FINANCIAL DISCLOSURE(S): The authors have no proprietary or
      commercial interest in any of the materials discussed in this article.

PMID- 22986110
TI  - Laboratory evidence of sustained chronic inflammatory reaction in retinitis
      pigmentosa.
AB  - PURPOSE: To study the nature of retinal inflammatory response in rd10 mice, an
      animal model of retinitis pigmentosa (RP), and to investigate the effect of an
      antioxidant on retinal inflammation and photoreceptor apoptosis. DESIGN:
      Experimental study. PARTICIPANTS AND CONTROLS: This study included 42 untreated
      rd10 mice, 30 N-acetylcysteine (NAC)-treated rd10 mice, and 20 C57BL/6 mice as
      controls. METHODS: Real-time polymerase chain reaction (PCR) was performed to
      evaluate the expression levels of inflammatory factors (proinflammatory cytokines
      and chemokines) in rd10 mouse retinas. Rd10 mice were treated with an antioxidant
      NAC, and its effect on retinal inflammation and photoreceptor apoptosis were
      examined by immunohistochemistry. MAIN OUTCOME MEASURES: Real-time PCR and
      immunohistochemistry. RESULTS: We demonstrated sequential events involving
      increased expression of proinflammatory cytokines and chemokines, activation of
      microglia, and photoreceptor apoptosis during retinal degeneration of rd10 mice.
      Furthermore, antioxidant treatment with NAC prevented the photoreceptor cell
      death along with suppression of inflammatory factors and microglial activation.
      CONCLUSIONS: Sustained chronic inflammatory reaction may contribute to the
      pathogenesis of retinal degeneration in rd10 mice, suggesting interventions for
      ocular inflammatory reaction using antioxidants as a potential treatment for
      patients with RP. FINANCIAL DISCLOSURE(S): The authors have no proprietary or
      commercial interest in any of the materials discussed in this article.

PMID- 22986111
TI  - Phacoemulsification versus trabeculectomy in medically uncontrolled chronic angle
      closure glaucoma without cataract.
AB  - OBJECTIVE: To compare phacoemulsification versus trabeculectomy with adjunctive
      mitomycin C in medically uncontrolled chronic angle-closure glaucoma (CACG)
      without cataract. DESIGN: Prospective, randomized clinical trial. PARTICIPANTS:
      Fifty medically uncontrolled CACG eyes without cataract of 50 patients.
      INTERVENTION: Patients were randomized into undergoing either phacoemulsification
      or trabeculectomy with adjunctive mitomycin C. After surgery, patients were
      followed up every 3 months for 2 years. MAIN OUTCOME MEASURES: Intraocular
      pressure (IOP) and requirement for glaucoma drugs. RESULTS: Twenty-six CACG eyes
      were randomized to receive phacoemulsification, and 24 eyes underwent
      trabeculectomy with mitomycin C. Phacoemulsification and trabeculectomy resulted
      in significant and comparable IOP reduction at 24 months after surgery (reduction
      of 8.4 mmHg or 34% for phacoemulsification vs. 8.9 mmHg or 36% for
      trabeculectomy; P=0.76). Over first 24 months, trabeculectomy-treated eyes
      required on average 1.1 fewer drugs than phacoemulsification-treated eyes
      (P<0.001). However, trabeculectomy was associated with significantly more
      surgical complications than phacoemulsification (46% vs. 4%; P=0.001). Eight
      (33%) of 24 trabeculectomy eyes demonstrated cataract during follow-up.
      CONCLUSIONS: Both phacoemulsification and trabeculectomy are effective in
      reducing IOP in medically uncontrolled CACG eyes without cataract. Trabeculectomy
      is more effective than phacoemulsification in reducing dependence on glaucoma
      drugs, but is associated with more complications. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 22986112
TI  - The United Kingdom Glaucoma Treatment Study: a multicenter, randomized, placebo
      controlled clinical trial: design and methodology.
AB  - OBJECTIVE: Elevated intraocular pressure (IOP) is a major risk factor for the
      deterioration of open-angle glaucoma (OAG); medical IOP reduction is the standard
      treatment, yet no randomized placebo-controlled study of medical IOP reduction
      has been undertaken previously. The United Kingdom Glaucoma Treatment Study
      (UKGTS) tests the hypothesis that treatment with a topical prostaglandin analog,
      compared with placebo, reduces the frequency of visual field (VF) deterioration
      events in OAG patients by 50% over a 2-year period. DESIGN: The UKGTS is a
      randomized, double-masked, placebo-controlled, multicenter treatment trial for
      OAG. PARTICIPANTS: Five hundred sixteen newly diagnosed (previously untreated)
      patients with OAG were recruited prospectively at 10 centers between 2007 and
      2010. METHODS: Patients were assigned by concealed telephone allocation to
      treatment with a prostaglandin analog (latanoprost 0.005%) or placebo. The
      observation period was 2 years, with subjects monitored by VF testing,
      quantitative imaging, optic disc photography, and tonometry at 11 visits. Data
      were acquired according to novel protocols optimized for the analysis of
      deterioration velocity. The sample size was determined for a 2-sided error of
      alpha=0.05 to detect the difference between 24% and 11% in incident deterioration
      over a 24-month follow-up at 90% power and assuming a 25% attrition rate. MAIN
      OUTCOME MEASURES: The primary outcome was time to VF deterioration within 24
      months. Secondary outcomes included the deterioration velocity of VF and
      quantitative imaging measures and the relationship between these velocities and
      risk factors for deterioration. RESULTS: The study design enabled a short trial
      with a 2-year observation period and provided data that can be used to assess the
      feasibility of further shortening trial duration with the progression velocity of
      VF and structural imaging measurements as outcomes. CONCLUSIONS: The UKGTS is the
      first randomized, placebo-controlled trial to evaluate the efficacy of medical
      treatment in reducing VF deterioration in OAG. The measurement of deterioration
      velocity and inclusion of quantitative imaging has the potential to reduce the
      number of patients and duration required for subsequent clinical trials. This
      trial also will quantify risk factors for deterioration, enabling more precise
      risk profiling of patients and the development of patient management protocols.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 22986113
TI  - Acute postoperative Bacillus cereus endophthalmitis mimicking toxic anterior
      segment syndrome.
AB  - OBJECTIVE: To study the clinicomicrobiologic characteristics and treatment
      outcomes in eyes with acute postoperative endophthalmitis (APE) owing to Bacillus
      cereus from a tertiary eye-care center. DESIGN: Retrospective, interventional
      case series. PARTICIPANTS: Case records of all eyes with culture-proven APE
      attributable to B cereus from January 2000 to May 2011 were identified from a
      computerized database and evaluated. METHODS: Clinical features at time of
      presentation, microbiological characteristics, and treatment measures were
      recorded. A thorough literature search using PubMed and the Cochrane Library
      databases was done to identify all cases of APE owing to Bacillus species
      reported to date and clinical characteristics of these eyes was compared with our
      series. MAIN OUTCOME MEASURES: Structural (globe salvage) and functional (visual
      rehabilitation) outcomes at last follow-up visit. RESULTS: We found 6 sporadic
      cases that experienced APE during the study period. All eyes had a fulminant
      onset within the first 24 hours of cataract surgery with extremely high
      intraocular pressure (IOP) and corneal edema similar to toxic anterior segment
      syndrome (TASS). However, these eyes progressed rapidly to develop corneal
      infiltrates, scleral and uveal tissue necrosis with hyphema, brownish exudates in
      anterior chamber and necrotizing retinitis within hours despite immediate
      initiation of intravitreal pharmacotherapy and vitrectomy. All eyes demonstrated
      gram-positive bacilli from the aqueous and B cereus was isolated, which was
      sensitive to conventional antibiotics except penicillin. Two eyes required
      therapeutic keratoplasty, combined with a scleral patch graft in 1 eye, 1 eye was
      eviscerated after 48 hours of onset of symptoms, and 2 eyes experienced
      phthisical changes within 10 days of onset. CONCLUSIONS: We found that APE owing
      to B cereus has an onset within 12 to 24 hours of intraocular surgery and
      simulates TASS in the first few hours. The clinical course is marked by rapidly
      worsening necrotizing infection, leading to very poor outcomes despite early
      institution of appropriate therapy. One must closely observe every case of TASS
      that presents with intense pain and extremely high IOP and rule out APE owing to
      B cereus with microbiologic testing. FINANCIAL DISCLOSURE(S): The authors have no
      proprietary or commercial interest in any of the materials discussed in this
      article.

PMID- 22986114
TI  - Brow ptosis after temporal artery biopsy: incidence and associations.
AB  - OBJECTIVE: Temporal artery biopsy (TAB), performed for the diagnosis of giant
      cell arteritis, has a low reported rate of complications. One complication is
      damage to the facial nerve branches, which can result in brow ptosis and/or
      orbicularis oculi weakness. However, the incidence of facial nerve damage after
      TAB is unknown. DESIGN: Prospective, institutional review board-approved study of
      all TABs performed by 2 surgeons over a 17-month period. PARTICIPANTS: Seventy
      patients undergoing 77 TABs. METHODS: Demographic data, including age, gender,
      and race/ethnicity, were collected for all patients. Frontalis and orbicularis
      oculi muscle function were evaluated pre- and postoperatively in all patients.
      The use of blood thinners, location of the incision, length of incision and
      biopsy, biopsy results, and procedure difficulty were recorded. Incidence of
      postoperative facial nerve damage, other complications, and rates of facial nerve
      recovery were evaluated. Analysis of variables was performed for any potential
      correlation with facial nerve damage. MAIN OUTCOME MEASURES: Incidence of facial
      nerve damage. RESULTS: Analysis included 75 biopsies performed in 68 patients.
      The majority of the patients were white (75.0%) and female (67.6%). The mean age
      was 72.6 years (range, 51-96). Postoperative facial nerve damage was found in 12
      patients (16.0%) and 58.3% of these fully resolved at an average of 4.43 months
      (range, 1-6). Two patients (2.7%) had postoperative infections. There was no
      correlation with facial nerve damage and use of blood thinners, biopsy result,
      surgeon, procedure difficulty, incision length, or specimen length. The distance
      from the incision to both the orbital rim and the brow was significant: Incisions
      farther from the orbital rim and brow were less likely to have postoperative
      facial nerve damage. CONCLUSIONS: There is a 16.0% incidence of postoperative
      facial nerve damage with TABs, which recovers fully in over half of patients.
      Incisions closer to the orbital rim and brow were more likely to have
      postoperative facial nerve dysfunction. Incisions >35 mm from both the orbital
      rim and brow or above the brow were less likely to have postoperative brow
      ptosis. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial
      interest in any of the materials discussed in this article.

PMID- 22986115
TI  - Nonexercise activity thermogenesis: a way forward to treat the worldwide obesity
      epidemic.

PMID- 22986118
TI  - A disposable biosensor based on immobilization of laccase with silica spheres on
      the MWCNTs-doped screen-printed electrode.
AB  - BACKGROUND: Biosensors have attracted increasing attention as reliable
      analytical instruments in in situ monitoring of public health and environmental
      pollution. For enzyme-based biosensors, the stabilization of enzymatic activity
      on the biological recognition element is of great importance. It is generally
      acknowledged that an effective immobilization technique is a key step to achieve
      the construction quality of biosensors. RESULTS: A novel disposable biosensor was
      constructed by immobilizing laccase (Lac) with silica spheres on the surface of
      multi-walled carbon nanotubes (MWCNTs)-doped screen-printed electrode (SPE).
      Then, it was characterized in morphology and electrochemical properties by
      scanning electron microscopy (SEM) and cyclic voltammetry (CV). The
      characterization results indicated that a high loading of Lac and a good
      electrocatalytic activity could be obtained, attributing to the porous structure,
      large specific area and good biocompatibility of silica spheres and MWCNTs.
      Furthermore, the electrochemical sensing properties of the constructed biosensor
      were investigated by choosing dopamine (DA) as the typical model of phenolic
      compounds. It was shown that the biosensor displays a good linearity in the range
      from 1.3 to 85.5 MUM with a detection limit of 0.42 MUM (S/N = 3), and the
      Michaelis-Menten constant (Kmapp) was calculated to be 3.78 MUM. CONCLUSION: The
      immobilization of Lac was successfully achieved with silica spheres to construct
      a disposable biosensor on the MWCNTs-doped SPE (MWCNTs/SPE). This biosensor could
      determine DA based on a non-oxidative mechanism in a rapid, selective and
      sensitive way. Besides, the developed biosensor could retain high enzymatic
      activity and possess good stability without cross-linking reagents. The proposed
      immobilization approach and the constructed biosensor offer a great potential for
      the fabrication of the enzyme-based biosensors and the analysis of phenolic
      compounds.

PMID- 22986117
TI  - Chemotherapeutic agents increase the risk for pulmonary function test
      abnormalities in patients with multiple myeloma.
AB  - Case reports of pulmonary toxicity have been published regarding bortezomib,
      lenalidomide, and thalidomide but there are no published reports looking at the
      possible long-term pulmonary effects of these medications. This article describes
      a possible relationship between the administration of bortezomib and thalidomide
      and the development of pulmonary function test (PFT) abnormalities. It also
      suggests that routine pulmonary function testing may be required in patients
      receiving these medications until larger studies can be performed to confirm this
      observation. BACKGROUND: Multiple myeloma is a common malignancy accounting for
      approximately 1% of all malignancies worldwide. Bortezomib, lenalidomide, and
      thalidomide are immunomodulatory derivatives that are used in the treatment of
      multiple myeloma (MM). There have been case reports of pulmonary disease
      associated with these agents, but the effect of these agents on pulmonary
      function test (PFT) results is unknown. PATIENTS AND METHODS: We reviewed the
      records of 343 patients with MM who underwent PFTs before autologous stem cell
      transplantation. One hundred nine patients had not received any of the 3
      medications, whereas 234 had received 1 or more of these agents. RESULTS:
      Patients exposed to bortezomib were more likely to have obstructive PFT results
      (P = .015) when compared with patients not exposed to this medication.
      Restrictive PFT results were more likely after exposure to thalidomide (P =
      .017). A logistic regression model was performed and when adjusted for age, sex,
      Durie-Salmon (DS) stage, body mass index (BMI), time from diagnosis to
      transplantation in days, and smoking history, the odds of obstruction were 1.96
      times higher for patients who received bortezomib. The odds of restriction were
      1.97 times higher after exposure to thalidomide. CONCLUSION: There appears to be
      a risk of PFT abnormalities developing in patients treated with bortezomib and
      thalidomide.

PMID- 22986119
TI  - [Sarcoidosis and liver involvement: a case series of 25 patients].
AB  - PURPOSE: Sarcoidosis is a systemic disease of unknown etiology that may affect
      many organs including the liver. Our aims were to determine the clinical,
      paraclinical and therapeutic characteristics of patients with liver sarcoidosis
      and to compare, on the one hand, the revealing hepatic involvement to the non
      revealing form and, on the other hand, sarcoidosis with and without liver
      disease. METHODS: A retrospective and descriptive study over 14 years of 25
      patients with liver involvement selected from 56 cases of systemic sarcoidosis.
      RESULTS: The study population was composed of 18 females and seven males. The
      mean age was 48.2 years. Liver involvement was the presenting manifestation in
      56% of cases. The functional history was dominated by general signs and abdominal
      pain. Hepatomegaly was present in ten patients. Biological abnormalities were
      identified in 84% of the cases with cholestasis (80%) and cytolysis (36%).
      Abdominal tomography showed hepatomegaly in 68.4% of the patients. Hepatic
      impairment was histologically confirmed in 16 patients. Granulomas were located
      in portal region (18.8%), in lobular region (12.5%) and in both (56.2%).
      Necroinflammatory lesions were found in 56.2%, cholestatic lesions in 18.8% and
      vascular lesions in 6.3%. Portal fibrosis and cirrhosis were seen in 25% and
      6.3%, respectively. Twenty-four patients were treated with corticosteroids with 1
      mg/kg per day (66.7%) and 0.5 mg/kg per day (33.3%). Under treatment, the
      response was complete in 81% and partial in 9.5%. One patient had no response.
      The liver involvement was significantly associated with general signs, renal
      failure and lymphopenia. Abdominal pain, hepatomegaly and lymph node were
      significantly associated with the revealing form. CONCLUSION: Liver involvement
      is frequent in sarcoidosis and commonly asymptomatic. Hepatomegaly is the most
      common clinical sign. Biological disturbance are present in 20 to 40% of the
      patients. The treatment is based essentially on corticosteroid therapy.

PMID- 22986120
TI  - [Thrombotic microangiopathy with anti-ADAMTS 13 antibodies revealing an acute Q
      fever].
AB  - INTRODUCTION: Q fever can commonly mimic systemic diseases, leading to several
      immunological manifestations. Thrombotic micro-angiopathies manifest as a
      spectrum of related disorders in the form of thrombocytopenic purpura and
      hemolytic uremic syndrome. CASE REPORT: We report a 77-year-old woman, who
      presented an acquired thrombotic microangiopathy with renal expression associated
      with the presence of anti-ADAMTS 13 antibodies, which occurred during an acute
      infection by Coxiella burnetii (acute Q fever). CONCLUSION: Auto-immune disorders
      are well-known in chronic or acute Q fever but to our knowledge, this is the
      first reported observation of thrombotic microangiopathy with anti-ADAMTS 13
      antibodies.

PMID- 22986122
TI  - Differences in egg deposition of corticosterone and embryonic expression of
      corticosterone metabolic enzymes between slow and fast growing broiler chickens.
AB  - Glucocorticoids (GCs) are vital for embryonic development and their bioactivity
      is regulated by the intracellular metabolism involving 11beta-hydroxysteroid
      dehydrogenases (11beta-HSDs) and 20-hydroxysteroid dehydrogenase (20-HSD). Here
      we sought to reveal the differences in egg deposition of corticosterone and
      embryonic expression of corticosterone metabolic enzymes between slow and fast
      growing broiler chickens (Gallus gallus). Eggs of fast-growing breed contained
      significantly higher (P<0.05) corticosterone in the yolk and albumen, compared
      with that of a slow-growing breed. 11beta-HSD1 and 11beta-HSD2 were expressed in
      relatively higher abundance in the liver, kidney and intestine, following similar
      tissue-specific ontogenic patterns. In the liver, expression of both 11beta-HSD1
      and 11beta-HSD2 was upregulated (P<0.05) towards hatching, yet 20-HSD displayed
      distinct pattern showing a significant decrease (P<0.05) on posthatch day 1 (D1).
      Hepatic mRNA expression of 11beta-HSD1 and 11beta-HSD2 was significantly higher
      in fast-growing chicken embryos at all the embryonic stages investigated and so
      was the hepatic protein content on embryonic day of 14 (E14) for 11beta-HSD1 and
      on E14 and D1 for 11beta-HSD2. 20-HSD mRNA was higher in fast-growing chicken
      embryos only on E14. Our data provide the first evidence that egg deposition of
      corticosterone, as well as the hepatic expression of glucocorticoid metabolic
      enzymes, differs between fast-growing and slow-growing chickens, which may
      account, to some extent, for the breed disparities in embryonic development.

PMID- 22986121
TI  - Pex11alpha in brown trout (Salmo trutta f. fario): Expression dynamics during the
      reproductive cycle reveals sex-specific seasonal patterns.
AB  - A negative correlation between female gonadal maturation kinetics and size
      variations of hepatic peroxisomes was earlier documented in brown trout, as a
      probable impact of serum estrogen changes during the reproductive cycle. Herein,
      we investigated whether the organelle volume/surface dynamics seen in female
      brown trout liver peroxisomes - without numerical changes within each hepatocyte 
      is followed by variations in the expression of the membrane peroxisome protein
      Pex11alpha gene. For comparison, we also studied males. We find in females a
      seasonal variation with the highest Pex11alpha expression in February, which was
      statistically different from all other tested periods. Overall, the expression of
      PEX11alpha had over a fivefold decrease from February to September. This period
      coincides with the reproductive transition between the earlier post-spawning
      gonadal remodeling and preparatory staging and the pre-spawning period. Males did
      not show changes. Our approach allowed the first characterization of a peroxin
      gene in a teleost, the Pex11alpha, while offering a correlation scenario were, as
      we hypothesized, the peroxisomal size kinetics is paralleled by membrane-related
      gene alterations (measured herein as proxy of Pex11alpha gene expression). Our
      data support and expand previous results on the regulation, function and
      morphology of peroxisome dynamics in brown trout, with a broader interest.

PMID- 22986123
TI  - A trans European Union difference in the decline in trans fatty acids in popular
      foods: a market basket investigation.
AB  - OBJECTIVES: To minimise the intake of industrial trans fatty acids (I-TFA) some
      countries have introduced labelling, while others have introduced legislative
      limits on the content of I-TFA in food. However, most countries still rely on
      food producers to voluntarily reduce the I-TFA content in food. The objective of
      the present study was to investigate the efficiency of these strategies in the
      EU. DESIGN: The potential consumption of I-TFA was assessed in a market basket
      investigation by analysing the I-TFA content in popular foods. SETTING: A
      standardised purchase methodology was used in 16 EU countries in 2005 and again
      in 2009. SAMPLES: Seventy servings of French fries and chicken nuggets, 90
      packages of microwave popcorn, and 442 samples of biscuits/cakes/wafers with
      'partially hydrogenated vegetable fat' listed high on the list of ingredients
      were analysed. A high-trans menu was defined as a large serving of French fries
      and nuggets, 100 g of microwave popcorn and 100 g of biscuits/wafers/cakes.
      RESULTS: In 2005, a high-trans menu provided above 30 g of I-TFA in five EU
      countries in Eastern Europe and 20-30 g in eight EU countries in Western Europe.
      In 2009 the values in Hungary, Poland and the Czech Republic remained high
      between 10 and 20 g, whereas they were less than 2 g in Germany, France and the
      UK. CONCLUSIONS: In 2009 contents of I-TFA in popular foods in Western Europe
      appear low but, in spite of some reduction, still high in Eastern European EU
      countries. These findings suggest that millions of people in the EU still consume
      I-TFA in amounts that substantially increase their risk of coronary heart
      disease.

PMID- 22986124
TI  - Mitochondrial diseases: translation matters.
AB  - Mitochondrial diseases comprise a heterogeneous group of disorders characterized
      by compromised energy production. Since the early days of mitochondrial medical
      genetics, it has been known that these can be caused by defects in mitochondrial
      protein synthesis. However, only in recent years have we begun to develop a
      broader picture of the array of proteins required for mitochondrial translation.
      With this new knowledge has come the realization that there are many more
      neurological and other, diseases attributable to impaired mitochondrial
      translation than previously thought. Perturbation of any part of this intricate
      machinery, from the primary sequence of transfer or ribosomal RNAs, to the
      proteolytic processing of ribosomal proteins, can cause mitochondrial dysfunction
      and disease. In this review we discuss the current understanding of the
      mechanisms and factors involved in mammalian mitochondrial translation, and the
      diverse pathologies resulting when it malfunctions. This article is part of a
      Special Issue entitled 'Mitochondrial function and dysfunction in
      neurodegeneration'.

PMID- 22986125
TI  - Trauma and suicidality in war affected communities.
AB  - PURPOSE: The aim was to assess whether experiences of war trauma remain directly
      associated with suicidality in war affected communities when other risk factors
      are considered. MATERIALS AND METHODS: In the main sample 3313 participants from
      former Yugoslavia who experienced war trauma were recruited using a random
      sampling in five Balkan countries. In the second sample 854 refugees from former
      Yugoslavia recruited through registers and networking in three Western European
      countries. Sociodemographic and data on trauma exposure, psychiatric diagnoses
      and level of suicidality were assessed. RESULTS: In the main sample 113
      participants (3.4%) had high suicidality, which was associated with number of
      potentially traumatic war experiences (odds ratio 1.1) and war related
      imprisonment (odds ratio 3) once all measured risk factors were considered. These
      associations were confirmed in the refugee sample with a higher suicidality rate
      (10.2%). DISCUSSION AND CONCLUSIONS: Number of potentially traumatic war
      experiences, in particular imprisonment, may be considered as a relevant risk
      factor for suicidality in people affected by war.

PMID- 22986126
TI  - Lifetime and 12-month prevalence rates of sub-clinical psychosis symptoms in a
      community cohort of 50-year-old individuals.
AB  - BACKGROUND: Estimation of prevalence rates of sub-clinical psychosis symptoms can
      vary considerably depending on the methodology used. Furthermore, discussions are
      ongoing how prevalence rates may differ across various syndromes. METHOD: We
      analyzed data from the prospective Zurich Study, assessing sub-clinical psychosis
      with a semi-structured clinical interview in a community cohort of 50 years old
      individuals. The higher-order factors of psychosis symptoms were analyzed with
      confirmatory factor analysis to validate the a priori specified symptom
      structure. Further associations were examined with contingency tables and
      logistic regressions. RESULTS: The confirmatory factor analysis was consistent
      with a structure with four higher-order syndromes. Those different syndromes were
      labeled "thought disorder" (lifetime prevalence=10.6%), "ego disorder" (4.8%),
      "hallucination" (9.7%), and "schizotypy" (28.2%). A strong discrepancy was noted
      between the 12-month prevalence of any symptoms and those considered to be
      severe. Twelve-month prevalence rates of distressful syndromes ranged from 0.1%
      for hallucinations up to 6.6% for schizotypy. The most strongly interrelated
      syndromes were thought disorder and ego disorder (OR=12.4). CONCLUSION: Our
      findings indicate a continuity of sub-clinical psychosis within the general
      population even though only a small proportion suffers from distressing symptoms.
      Our analyses showed that the syndromes identified here are similar to those found
      in full-blown schizophrenia, albeit in an attenuated form.

PMID- 22986127
TI  - Is ADHD severity in adults associated with the lifetime prevalence of comorbid
      depressive episodes and anxiety disorders?
AB  - PURPOSE: The objective of the present study was to examine the association
      between ADHD severity and the lifetime prevalence of comorbid depressive episodes
      and anxiety disorders in adults with ADHD. SUBJECTS/MATERIALS AND METHODS:
      Analyses were based on data of the Conner's Adult ADHD Rating Scale (CAARS) and a
      parent study examining the epidemiology of adult ADHD in 17 GP practices in
      Budapest, Hungary. Subjects between 18 and 60 years were included in the
      screening phase (n=3529). Out of 279 positively screened subjects 161
      participated in a clinical interview and completed the CAARS to confirm the
      diagnosis. We applied four diagnostic criteria: "DSM-IV"; "No-onset" (DSM-IV
      criteria without the specific requirement for onset); "Symptoms-only" (DSM-IV
      symptom criterion only); and "Reduced symptoms-only" (DSM-IV symptom criterion
      with a reduced threshold for symptom count). The MINI PLUS 5.0 was used to assess
      psychiatric comorbidity. RESULTS: ADHD severity, as measured by the CAARS ADHD
      Index, showed a significant positive association with the prevalence of comorbid
      depressive episodes in all but the "ADHD_No-onset" group ("DSM-IV": F[1.23]=8.39,
      P=0.0081; "No-onset": F(1.27)=0.97, P=0.3346; "Symptoms-only": F[1.55]=30.79,
      P<0.0001; "Reduced symptoms-only": F(1.62)=26.69, P<0.0001). DISCUSSION AND
      CONCLUSION: Results indicate that ADHD symptom severity increases in association
      with lifetime comorbidity with depression.

PMID- 22986128
TI  - The effect of serotonin transporter gene promoter polymorphism on adolescent and
      adult ADHD symptoms and educational attainment: a longitudinal study.
AB  - INTRODUCTION: The purpose of this longitudinal study was to investigate the
      relationship between the 5-HTTLPR genotype, symptoms of ADHD in adolescence and
      adulthood, and educational attainment in a population representative sample.
      Neuroticism, depressive symptoms and general mental abilities were controlled for
      as possible confounding factors. METHODS: ADHD symptoms were reported at age 15
      and 18 by teachers using the Hyperactivity Scale of af Klinteberg and SNAP-IV,
      and self-reported at age 25 using the ASRS. Data about education were reported at
      age 25. RESULTS: At age 15, subjects with the l/l genotype had more concentration
      difficulties compared to s-allele carriers, and they also had more inattention
      symptoms according to SNAP-IV at age 18. These results were not altered by taking
      neuroticism or depressive symptoms into account. No 5-HTTLPR genotype effect on
      self-reported ADHD symptoms at age 25 was found. Inattention symptoms in
      adolescence were associated with lower education in young adulthood. The
      proportion of subjects with higher education at age 25 was significantly larger
      among s/s genotype compared to the l/l or s/l genotype. CONCLUSIONS: The l/l
      genotype of the 5-HTTLPR is associated with inattentive symptoms during
      adolescence in the general population, and increases the likelihood of inferior
      educational level in young adulthood.

PMID- 22986129
TI  - Investigating the interactions between cations, peroxidation substrates and G
      quadruplex topology in DNAzyme peroxidation reactions using statistical testing.
AB  - Cations affect the topology and enzymatic proficiency of most macromolecular
      catalysts but the role of cations in DNAzyme peroxidation reactions remains
      unresolved. Herein, we use statistical methods (ANOVA, t-test and Wilcoxon Mann
      Whitney non-parametric test) to demonstrate that there are strong associations
      between cations, DNAzyme topology, peroxidation substrate and peroxidation rates
      of G-quadruplex peroxidises. Ammonium cation was found to be superior to all
      tested cations, including potassium. A t-test indicated that NH(4)(+) was better
      than K(+) with a p-value=0.05. Interestingly, the nature of the peroxidation
      substrate employed affected the dependence of peroxidation rate on the cation
      present and of the three substrates tested, 2,2'-azino-bis (3
      ethylbenzothiazoline-6-sulfonic acid (ABTS), tyramine and 3,3',5,5'
      tetramethylbenzidine (TMB), ABTS was the most sensitive to the nature of cation
      present.

PMID- 22986130
TI  - Versatile nanocomposites in phosphoproteomics: a review.
AB  - Protein phosphorylation is one of the most important post-translational
      modifications. Phosphorylated peptides are present in low abundance in blood
      serum but play a vital role in regulatory mechanisms and may serve as casual
      factors in diseases. The enrichment and analysis of phosphorylated peptides
      directly from human serum and mapping the phosphorylation sites is a challenging
      task. Versatile nanocomposites of different materials have been synthesized using
      simple but efficient methodologies for their enrichment. The nanocomposites
      include magnetic, coated, embedded as well as chemically derivatized materials.
      Different base materials such as polymers, carbon based and metal oxides are
      used. The comparison of nanocomposites with respective nanoparticles provides
      sufficient facts about their efficiency in terms of loading capacity and capture
      efficiency. The cost for preparing them is low and they hold great promise to be
      used as chromatographic materials for phosphopeptide enrichment. This review
      gives an overview of different nanocomposites in phosphoproteomics, discussing
      the improved efficiency than the individual counterparts and highlighting their
      significance in phosphopeptide enrichment.

PMID- 22986131
TI  - Ordered mesoporous carbon for electrochemical sensing: a review.
AB  - With its well-ordered pore structure, high specific surface area and tunable pore
      diameters in the mesopore range, ordered mesoporous carbon (OMC) is suitable for
      applications in catalysis and sensing. We report recent applications of OMC in
      electrochemical sensors and biosensors. After a brief description of the
      electrochemical properties, the functionalization of the OMC for improvement of
      the electrocatalytic properties is then presented. We show how the ordered
      mesostructure of OMC is very important in those applications. The high density of
      edge plane-like defective sites (EDSs), oxygen-containing groups and a large
      surface area on OMC may provide many favorable sites for electron transfer to
      compounds, which makes OMC a potential novel material for an investigation of the
      electrochemical behavior of substances. Moreover, the structural capabilities of
      OMC at the scale of a few nanometers agree with immobilization of other
      electrocataytic substances. Interesting properties of this material may open up a
      new approach to study the electrochemical determination of other biomolecules.

PMID- 22986132
TI  - Magnetic solid-phase extraction of sulfonylurea herbicides in environmental water
      samples by Fe3O4@dioctadecyl dimethyl ammonium chloride@silica magnetic
      particles.
AB  - A magnetic solid phase extraction (MSPE) method coupled with high-performance
      liquid chromatography (HPLC) was proposed for the determination of five
      sulfonylurea herbicides (bensulfuron-methyl, prosulfuron, pyrazosulfuron-ethyl,
      chlorimuron-ethyl and triflusulfuron-methyl) in environmental water samples. The
      magnetic adsorbent was prepared by incorporating Fe(3)O(4) nanoparticles and
      surfactant into a silica matrix according to a sol-gel procedure, which can
      provide surfactant free extracts during the eluting step to avoid chromatographic
      interference. The prepared adsorbent was used to extract the sulfonylurea
      herbicides in several kinds of water samples. The main factors affecting the
      extraction efficiency, including desorption conditions, extraction time, sample
      volume, and sample solution pH were optimized. Under the optimum conditions, good
      linearity was obtained within the range of 0.2-50.0 MUg L(-1) for all analytes,
      with correlation coefficients ranging from 0.9993 to 0.9999. The enrichment
      factors were between 1200 and 1410, and the limits of detection were between
      0.078 and 0.10 MUg L(-1). The proposed method was successfully applied in the
      analysis of sulfonylurea herbicides in environmental samples (tap, reservoir,
      river, and rice field). The recoveries of the method ranged between 80.4% and
      107.1%. This study reported for the first time the use of MSPE procedure in the
      preconcentration of sulfonylurea herbicides in environmental samples. The
      procedure proved to be efficient, environmentally friendly, and fast.

PMID- 22986133
TI  - The use of copper(II) isonicotinate-based micro-solid-phase extraction for the
      analysis of polybrominated diphenyl ethers in soils.
AB  - A micro-solid-phase extraction (MU-SPE) device was developed by filling
      copper(II) isonicotinate coordination polymer (Cu(4-C(5)H(4)N-COO)(2)(H(2)O)(4))
      into a porous polypropylene envelope, and the MU-SPE, coupling with gas
      chromatography (GC) with a micro-cell electron capture detector (MU-ECD), was
      used for extraction and determination of PBDEs in soils. Variables affecting
      extraction procedures, including temperature, water volume, extraction time, and
      desorption time, were investigated in a spiked soil, and the parameters were
      optimized. Under the optimal experimental conditions, the method detection limits
      for seven PBDEs (BDE-28, 47, 99, 100, 153, 154, and 183) were in the range of
      0.026-0.066 ng g(-1), and the reproducibility was satisfactory with the relative
      standard deviation in range of 1.3-10.1%. Good linear relationship between PBDEs
      concentrations and GC signals (defined as peak area) was obtained in the range
      between 0.1 and 200 ng g(-1). The recovery of the seven PBDEs by MU-SPE varied
      from 70 to 90%, which was comparable to that determined by accelerated solvent
      extraction method. Finally, the proposed method was used to determine PBDEs in
      several field-contaminated soils, and it was suggested that the MU-SPE is a
      promising alternative microextraction technique for the detection of PBDEs in
      soils.

PMID- 22986134
TI  - Impact of the sample matrix composition on the signal enhancement in the
      capillary electrophoretic separation of poliovirus samples.
AB  - The development of capillary electrophoretic applications aiming to provide
      reliable stability assessment of viral suspensions, to detect subviral particles
      from cell extracts or to study the interactions between virus particles and
      various biomolecules, cannot be done without a thorough understanding of the
      sample matrix contribution to the observed electrophoretic behaviour. The present
      study thoroughly investigates the effect of the sample matrix on the
      electrophoretic behaviour of poliovirus injected as sample plugs of 1%, 5% and
      12% effective capillary length. The effect of the sample matrix for three
      different poliovirus batches was evaluated. Additionally, simulated samples,
      obtained from concentrated poliovirus suspensions of high purity and diluted with
      commonly used lab buffers in order to obtain samples with either high or low
      conductivities, were also investigated. The goal of the study was to obtain a
      better understanding of the effect of the sample matrix on the signal
      enhancement, in order to define a general approach allowing a repeatable
      capillary electrophoretic (CE) separation of poliovirus from complex samples.
      This study clearly demonstrates that the sample matrix has an important influence
      on the sensitivity of the CE poliovirus separations. Translation of these
      observations into routine practice involves several compromises and a set of
      rules in order to reduce day-to-day variation and to maximize sensitivity.

PMID- 22986135
TI  - Tracing phenolic biosynthesis in Vitis vinifera via in situ C-13 labeling and
      liquid chromatography-diode-array detector-mass spectrometer/mass spectrometer
      detection.
AB  - Phenolic compounds in Vitis vinifera contribute important flavor, functionality,
      and health qualities to both table and wine grapes. The plant phenolic metabolic
      pathway has been well characterized, however many important questions remain
      regarding the influence of environmental conditions on pathway regulation. As a
      diagnostic for this pathway's regulation, we present a technique to incorporate a
      stable-isotopic tracer, L-phenyl-(13)C(6)-alanine (Phe(13)), into grape berries
      in situ and the accompanying high throughput analytical method based on LC-DAD
      MS/MS to quantify and track the label into phenylalanine metabolites. Clusters of
      V. vinifera cv. Cabernet Sauvignon, either near the onset of ripening or 4 weeks
      later, were exposed to Phe(13) in the vineyard. Phe(13) was present in berries 9
      days afterwards as well as labeled flavonols and anthocyanins, all of which
      possessed a molecular ion shift of 6 amu. However, nearly all the label was found
      in anthocyanins, indicating tight regulation of phenolic biosynthesis at this
      stage of maturity. This method provides a framework for examining the regulation
      of phenolic metabolism at different stages of maturity or under different
      environmental conditions. Additionally, this technique could serve as a tool to
      further probe the metabolism/catabolism of grape phenolics.

PMID- 22986136
TI  - A reliable solid phase microextraction-gas chromatography-triple quadrupole mass
      spectrometry method for the assay of selenomethionine and
      selenomethylselenocysteine in aqueous extracts: difference between selenized and
      not-enriched selenium potatoes.
AB  - A new analytical approach is exploited in the assay of selenium speciation in
      selenized and not selenium enriched potatoes based on the widely available solid
      phase microextraction (SPME) coupled to-GC-triple quadrupole mass spectrometry
      (SPME-GC-QqQ MS) method. The assay of selenomethionine (SeMet) and
      selenomethylselenocysteine (SeMeSeCys) in potatoes here reported provides clues
      to the effectiveness of SPME technique combined with gas chromatography-tandem
      mass spectrometry, which could be of general use. For the exploitation of the GC
      method, the selected analytes were converted into their N(O,S)-alkoxycarbonyl
      alkyl esters derivatives by direct treatment with alkyl chloroformate in aqueous
      extracts. The performance of five SPME fibers and three chloroformates were
      tested in univariate mode and the best results were obtained using the
      divinylbenzene/carboxen/polydimethylsiloxane fiber and propylchloroformate. The
      variables affecting the efficiency of SPME analysis were optimized by the
      multivariate approach of design of experiment (DoE) and, in particular, a central
      composite design (CCD) was applied. Tandem mass spectrometry in selected reaction
      monitoring (SRM) has allowed the elimination of matrix interferences, providing
      reconstructed chromatograms with well-resolved peaks and the achievement of very
      satisfactory detection and quantification limits. Both precision and recovery of
      the proposed protocol tested at concentration of 8 and 40 MUg kg(-1) (dry
      matter), offered values ranging from 82.3 to 116.3% and from 8.5 to 13.1% for
      recovery and precision, respectively. The application of the method to commercial
      samples of selenized and not selenium enriched potatoes proved that the Se
      fertilization increases significantly the concentration of these bioavailable
      selenoamino acids.

PMID- 22986137
TI  - Analytical performance of a triple quadrupole mass spectrometer compared to a
      high resolution mass spectrometer for the analysis of polybrominated diphenyl
      ethers in fish.
AB  - Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants used
      globally in many consumer products and industrial applications. Traditionally,
      gas chromatography-high resolution mass spectrometry (GC-HR-MS) is the method of
      choice for analysis of PBDEs in environmental samples because it offers high
      sensitivity and selectivity, resulting in less interferences. However, the
      specificity offered by gas chromatography-triple quadrupole tandem mass
      spectrometry (GC-QQQ-MS/MS), operated in selected reaction monitoring mode,
      provides a more affordable alternative to GC-HR-MS for the analysis of PBDEs in
      complex environmental samples. In this study, an analytical method was developed
      for the analysis of 41 PBDE congeners in fish using GC-QQQ-MS/MS. Results from
      the analysis of three fish species [lake trout (Salvelinus namaycush), yellow
      perch (Perca flavescens), and round goby (Neogobius melanostomus)] using GC-QQQ
      MS/MS were compared with those obtained by GC-HR-MS. These species were selected
      because they represent varying levels of lipid-rich matrix and contaminant loads.
      Instrumental limits of detection for the GC-QQQ-MS/MS ranged from 0.04 pg to 41
      pg, whereas those for the GC-HR-MS ranged from 5 pg to 85 pg. The PBDE values
      obtained from these two methods were highly correlated, R(2) values >0.7, for all
      three fish species, supporting the suitability of GC-QQQ-MS/MS for analysis of
      PBDEs in fish with varying fat content.

PMID- 22986138
TI  - Quality evaluation and species differentiation of Rhizoma coptidis by using
      proton nuclear magnetic resonance spectroscopy.
AB  - Rhizoma coptidis, a broadly used traditional Chinese medicine, derives from the
      dried rhizomes of Coptis chinensis Franch, Coptis deltoidea C.Y. Cheng et Hsiao
      and Coptis teeta Wall. Quantitative determination of protoberberine alkaloids in
      R. coptidis is critical for controlling its quality. In this study, a rapid,
      simple and accurate quantitative (1)H NMR (qNMR) method was developed for
      simultaneous determination of berberine, jatrorrhizine, epiberberine, coptisine,
      palmatine and columbamine in R. coptidis from the three species. Method
      validation was performed in terms of selectivity, precision, repeatability,
      stability, accuracy, robustness and linearity. The average recoveries obtained
      were in the range of 96.9-102.4% for all the six alkaloids. In addition, the qNMR
      data were analyzed with analysis of variance (ANOVA), hierarchical clustering
      analysis (HCA) and principal component analysis (PCA), and the results showed
      that the contents of the active alkaloids have significant difference among the
      three species. Compared with the conventional HPLC approach, the proposed qNMR
      method was demonstrated to be a powerful tool for quantifying the six alkaloids
      due to its unique advantages of high robustness, rapid analysis time and no need
      of standard compounds for calibration curves preparation. These findings indicate
      that this method has potential as a reliable method for quality evaluation of
      herb medicines, especially for protoberberine alkaloid-containing ones.

PMID- 22986139
TI  - Grafted Azure A modified electrodes as disposable beta-nicotinamide adenine
      dinucleotide sensors.
AB  - We report the in situ generation of aryl diazonium cations of Azure A, a redox
      active phenothiazine dye, by reaction between the corresponding aromatic
      aminophenyl group and sodium nitrite in 0.1 M HCl. The subsequent electrochemical
      reduction of these dye diazonium salts gives rise to conductive electrografted
      films onto screen-printed carbon (SPC) electrodes. The resulting Azure A films
      have a very stable and reversible electrochemical response and exhibit potent and
      persistent electrocatalytic behavior toward NADH oxidation. We have optimized the
      electrografting conditions in order to obtain SPC modified electrodes with high
      and stable electrocatalytic response. The kinetic of the reaction between the
      NADH and the redox active centers in the Azure A film has been characterized
      using cyclic voltammetry and single step chronoamperometry. The catalytic
      currents were proportional to the concentration of NADH giving rise to linear
      calibration plots up to a concentration of 0.5 mM with a detection limit of
      0.57+/-0.03 MUM and a sensitivity of 9.48 A mol cm(-2) MUM(-1). The precision of
      chronoamperometric determinations was found to be 2.3% for five replicate
      determinations of 3.95 MUM NADH. The great stability of such modified electrodes
      makes them ideal for their application in the development of biosensing platforms
      based on dehydrogenases.

PMID- 22986140
TI  - "Oxidative etching-aggregation" of silver nanoparticles by melamine and electron
      acceptors: an innovative route toward ultrasensitive and versatile functional
      colorimetric sensors.
AB  - An innovative and versatile functional colorimetric sensor for melamine (MA) and
      H(2)O(2) was developed with simplicity, excellent selectivity and
      ultrasensitivity. The detection mechanism was based on the "oxidative etching
      aggregation" of silver nanoparticles (AgNPs) by the cooperation effect of MA and
      electron acceptors such as H(2)O(2), ozone or Fe(NO(3))(3). The detection limits
      of this method for MA could reach as low as 0.08 nM, 0.16 nM and 3 nM when
      H(2)O(2), ozone or Fe(NO(3))(3) was used as an electron acceptor, respectively.
      When using H(2)O(2) as a typical electron acceptor, the method enabled the
      detection of H(2)O(2) with a detection limit of 0.2 nM. This proposed method
      offered a new way to design MA and H(2)O(2) sensors and might be easily extended
      to detect other nucleophilic reagents and electron acceptors based on
      colorimetric sensors.

PMID- 22986141
TI  - A highly sensitive label-free resonance light scattering assay of
      carcinoembryonic antigen based on immune complexes.
AB  - As a kind of glycoprotein, carcinoembryonic antigen (CEA) is the important tumor
      marker for clinical diagnosis of the presence or recurrence of cancer. In this
      work, a novel label-free resonance light scattering (RLS) spectral CEA assay was
      developed based on the combination of highly selective immunoreaction and
      ultrasensitive RLS technique. In Tris-HCl buffer solution (pH 7.5), the specific
      immunoreaction between CEA antigen and mouse anti-CEA formed immune complexes
      which had a maximum RLS spectral peak at 389.0 nm, with the existence of
      physiological saline and polyethylene glycol 20,000 (PEG 20,000). Under the
      optimal conditions, the magnitude of enhanced RLS intensity (DeltaI(RLS)) was
      proportional to the concentration of CEA in the range from 0.1 to 60 ng mL(-1),
      with a detection limit (LOD, 3sigma) of 0.03 ng mL(-1). The characteristics of
      RLS, the CEA immunocomplex, the immune response, the ratio of CEA antigen and
      mouse anti-CEA, and the optimum conditions of the immunoreaction have been
      investigated. The CEA concentrations of 20 serum specimens detected by the
      developed assay showed consistent results in comparison with those obtained by
      commercially available enzyme-linked immunosorbent assay (ELISA) kit. And this
      method has many satisfying merits including label-free, sensitivity and high
      selectivity.

PMID- 22986142
TI  - Tips and tricks for successful manual morcellation: a response to "vaginal
      morcellation: a new strategy for large gynecological malignant tumor extraction".

PMID- 22986143
TI  - Loss of function germline mutations in RAD51D in women with ovarian carcinoma.
AB  - OBJECTIVE: RAD51D, a gene in the Fanconi Anemia-BRCA homologous recombination
      pathway, has recently been shown to harbor germline mutations responsible for
      ovarian carcinoma in multiply affected families. We aimed to extend these results
      to ovarian carcinoma in the general population. METHODS: We sequenced RAD51D in
      germline DNA from 360 individuals with primary ovarian, peritoneal or fallopian
      tube carcinoma who were not selected for age of cancer onset or family history.
      We also sequenced RAD51D in 459 probands from 226 high risk breast cancer
      families who were wild type for 21 breast and ovarian cancer genes. RESULTS: Of
      360 cases, three (0.8%) carried loss-of-function mutations in RAD51D. All three
      subjects had ovarian carcinoma; one was also diagnosed with a synchronous
      endometrial carcinoma. Only one of the three subjects had a family history of
      breast or ovarian cancer. Combined with previous data for this series, 23.9% of
      women with unselected ovarian, fallopian tube, or peritoneal carcinoma carried a
      germline loss-of-function mutation in any of 13 tumor suppressor genes. Among the
      449 women and 10 men with familial breast cancer, none carried a loss of function
      mutation in RAD51D. CONCLUSIONS: These data support the previous observation that
      loss-of-function mutations in RAD51D predispose to ovarian carcinoma but not to
      breast carcinoma. We conclude that inherited ovarian cancer is highly
      heterogeneous genetically, and that approximately one in four ovarian carcinoma
      patients carry a germline mutation in a known tumor suppressor gene that confers
      high risk.

PMID- 22986144
TI  - Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent
      advanced cervix cancer: A gynecologic oncology group study.
AB  - BACKGROUND: Metastatic and recurrent, platinum resistant cervix cancer has an
      extremely poor prognosis. The Gynecologic Oncology Group has studied >20
      cytotoxic drugs or drug combinations in the second-line, phase II setting of
      advanced, drug resistant cervix cancer. METHODS: Nanoparticle, albumin-bound
      paclitaxel (nab-paclitaxel) was administered at 125 mg/m(2) IV over 30 minutes on
      days 1, 8 and 15 of each 28 day cycle to 37 women with metastatic or recurrent
      cervix cancer that had progressed or relapsed following first-line cytotoxic drug
      treatment. A flexible, 2-stage accrual design that allowed stopping early for
      lack of treatment activity was utilized. Because of slow patient accrual, the
      second stage was not completed. RESULTS: Of 37 patients enrolled, 2 were
      ineligible due to no prior cytotoxic chemotherapy, which left 35 eligible
      patients evaluable for response and tolerability. All of the eligible patients
      had 1 prior chemotherapy regimen and 27 of them had prior radiation therapy with
      concomitant cisplatin. The median number of nab-paclitaxel cycles were 4 (range 1
      15). Ten (28.6%; CI 14.6%-46.3%) of the 35 patients had a partial response and
      another 15 patients (42.9%) had stable disease. The median progression-free and
      overall survival were 5.0 and 9.4 months, respectively. The only NCI CTCAE grade
      4 event was neutropenia in 2 patients (5.7%) which resolved following dose
      reduction. Grade 3 neurotoxicity was reported in 1 (2.9%) patient and resolved to
      grade 2 following dose discontinuation. CONCLUSIONS: Nab-paclitaxel has
      considerable activity and moderate toxicity in the treatment of drug resistant,
      metastatic and recurrent cervix cancer.

PMID- 22986145
TI  - Comprehensive smoking bans and acute myocardial infarction among Medicare
      enrollees in 387 US counties: 1999-2008.
AB  - Restrictions on smoking in public places have become increasingly widespread in
      the United States, particularly since the year 2005. National-scale studies in
      Europe and local-scale studies in the United States have found decreases in
      hospital admissions for acute myocardial infarction (AMI) following smoking bans.
      The authors analyzed AMI admission rates for the years 1999-2008 in 387 US
      counties that enacted comprehensive smoking bans across 9 US states, using a
      study population of approximately 6 million Medicare enrollees aged 65 years or
      older. Effects of smoking bans on AMI admissions were estimated by using Poisson
      regression with linear and nonlinear adjustment for secular trend and random
      effects at the county level. Under the assumption of linearity in the secular
      trend of declining AMI, smoking bans were associated with a statistically
      significant ban-associated decrease in admissions for AMI in the 12 months
      following the ban. However, the estimated effect was attenuated to nearly zero
      when the assumption of linearity in the underlying trend was relaxed. This
      analysis demonstrates that estimation of potential health benefits associated
      with comprehensive smoking bans is challenged by the need to adjust for
      nonlinearity in secular trend.

PMID- 22986147
TI  - The acidic pH-induced structural changes in Pin1 as revealed by spectral
      methodologies.
AB  - Pin1 is closely associated with the pathogenesis of cancers and Alzheimer's
      disease (AD). Previously, we have shown the characteristics of the thermal
      denaturation of Pin1. Herein, the acid-induced denaturation of Pin1 was
      determined by means of fluorescence emission, synchronous fluorescence, far-UV
      CD, ANS fluorescence and RLS spectroscopies. The fluorescence emission spectra
      and the synchronous fluorescence spectra suggested the partially reversible
      unfolding (approximately from pH 7.0 to 4.0) and refolding (approximately from pH
      4.0 to 1.0) of the structures around the chromophores in Pin1, apparently with an
      intermediate state at about pH 4.0-4.5. The far-UV CD spectra indicated that
      acidic pH (below pH 4.0) induced the structural transition from alpha-helix and
      random coils to beta-sheet in Pin1. The ANS fluorescence and the RLS spectra
      further suggested the exposure of the hydrophobic side-chains of Pin1 and the
      aggregation of it especially below pH 2.3, and the aggregation possibly resulted
      in the formation of extra intermolecular beta-sheet. The present work primarily
      shows that acidic pH can induce kinds of irreversible structural changes in Pin1,
      such as the exposure of the hydrophobic side-chains, the transition from alpha
      helix to beta-sheet and the aggregation of Pin1, and also explains why Pin1 loses
      most of its activity below pH 5.0. The results emphasize the important role of
      decreased pH in the pathogenesis of some Pin1-related diseases, and support the
      therapeutic approach for them by targeting acidosis and modifying the
      intracellular pH gradients.

PMID- 22986148
TI  - On the role of Wnt/beta-catenin signaling in stem cells.
AB  - BACKGROUND: Stem cells are mainly characterized by two properties: self-renewal
      and the potency to differentiate into diverse cell types. These processes are
      regulated by different growth factors including members of the Wnt protein
      family. Wnt proteins are secreted glycoproteins that can activate different
      intracellular signaling pathways. SCOPE OF REVIEW: Here we summarize our current
      knowledge on the role of Wnt/beta-catenin signaling with respect to these two
      main features of stem cells. MAJOR CONCLUSIONS: A particular focus is given on
      the function of Wnt signaling in embryonic stem cells. Wnt signaling can also
      improve reprogramming of somatic cells towards iPS cells highlighting the
      importance of this pathway for self-renewal and pluripotency. As an example for
      the role of Wnt signaling in adult stem cell behavior, we furthermore focus on
      intestinal stem cells located in the crypts of the small intestine. GENERAL
      SIGNIFICANCE: A broad knowledge about stem cell properties and the influence of
      intrinsic and extrinsic factors on these processes is a requirement for the use
      of these cells in regenerative medicine in the future or to understand cancer
      development in the adult. This article is part of a Special Issue entitled
      Biochemistry of Stem Cells.

PMID- 22986146
TI  - Previous lung diseases and lung cancer risk: a pooled analysis from the
      International Lung Cancer Consortium.
AB  - To clarify the role of previous lung diseases (chronic bronchitis, emphysema,
      pneumonia, and tuberculosis) in the development of lung cancer, the authors
      conducted a pooled analysis of studies in the International Lung Cancer
      Consortium. Seventeen studies including 24,607 cases and 81,829 controls
      (noncases), mainly conducted in Europe and North America, were included (1984
      2011). Using self-reported data on previous diagnoses of lung diseases, the
      authors derived study-specific effect estimates by means of logistic regression
      models or Cox proportional hazards models adjusted for age, sex, and cumulative
      tobacco smoking. Estimates were pooled using random-effects models. Analyses
      stratified by smoking status and histology were also conducted. A history of
      emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence
      interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis
      conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis
      (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative
      risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung
      cancer risk. Among never smokers, elevated risks were observed for emphysema,
      pneumonia, and tuberculosis. These results suggest that previous lung diseases
      influence lung cancer risk independently of tobacco use and that these diseases
      are important for assessing individual risk.

PMID- 22986149
TI  - Like a rolling histone: epigenetic regulation of neural stem cells and brain
      development by factors controlling histone acetylation and methylation.
AB  - BACKGROUND: The development of the nervous system is a highly organized process
      involving the precise and coordinated timing of many complex events. These events
      require proper expression of genes promoting survival, differentiation, and
      maturation, but also repression of alternative cell fates and restriction of cell
      type-specific gene expression. SCOPE OF THE REVIEW: As the enzymes mediating post
      translational histone acetylation and methylation are regulating higher order
      chromatin structure and controlling gene transcription, knowledge of the roles
      for these enzymes becomes crucial for understanding neural development and
      disease. The widespread expression and general biological roles for chromatin
      modifying factors have hampered the studies of such enzymes in neural
      development, but in recent years, in vivo and in vitro studies have started to
      shed light on the various processes these enzymes regulate. In this review we
      summarize the implications of chromatin-modifying enzymes in neural development,
      with particular emphasis on enzymes regulating histone acetylation and
      methylation. MAJOR CONCLUSIONS: Enzymes controlling histone acetylation and
      methylation are involved in the whole process of neural development, from
      controlling proliferation and undifferentiated, "poised", state of stem cells to
      promoting and inhibiting neurogenic and gliogenic pathways and neuronal survival
      as well as neurite outgrowth. GENERAL SIGNIFICANCE: Aberrant enzymatic activities
      of histone acetyl transferases, deacetylases, and demethylases have been
      chemically and genetically associated with neural developmental disorders and
      cancer. Future studies may aim at linking the genetic and developmental studies
      to more in-depth biochemical characterization to provide a clearer picture of how
      to improve the diagnosis, prognosis, and treatment of such disorders. This
      article is part of a Special Issue entitled Biochemistry of Stem Cells.

PMID- 22986151
TI  - Transferrin-cisplatin specifically deliver cisplatin to HepG2 cells in vitro and
      enhance cisplatin cytotoxicity.
AB  - Cisplatin is a major broad-spectrum chemotherapeutic agent, however, its dose
      dependent side effects limit the administration of large doses. Presently,
      developing a drug targeted delivery system is suggested as one of the most
      promising approaches to minimize the side effects of cisplatin. Here, we found
      that each human serum transferrin (HTf) has the potential to bind with over 22
      cisplatins, and the complex of apo-HTf-cisplatin can specifically deliver
      cisplatin to HepG2 cells (human hepatocellular liver carcinoma cell line) in
      vitro, and facilitate HepG2 cells to apoptosis. Moreover, proteomics methods
      revealed that the abundances of 23 proteins in HepG2 cells were remarkably
      altered in response to cisplatin/apo-HTf-cisplatin exposure, and Realtime-PCR
      revealed that a number of important genes related to chemotherapeutic
      cytotoxicity and chemotherapeutic resistance are differentially transcribed
      between the HepG2 cells of cisplatin exposed and HTf-cisplatin exposed. The
      pathway analysis of the differentially expressed proteins and gene transcriptions
      indicated that those regulated proteins and gene transcriptions are involved in
      apoptosis regulation, transcription, cell cycle control, protein biosynthesis,
      energy metabolism, signal transduction, protein binding and other functions. It
      indicated that the cisplatin toxicity in HepG2 cell is diverse, the transport
      process has an effect on the cisplatin cytotoxicity, and the mechanism of the
      apoptosis of HepG2 cells induced by apo-HTf-cisplatin is different from that of
      cisplatin.

PMID- 22986152
TI  - Identification of urinary Gc-globulin as a novel biomarker for bladder cancer by
      two-dimensional fluorescent differential gel electrophoresis (2D-DIGE).
AB  - Improving the early detection rate and surveillance of bladder cancer remains a
      great challenge in medicine. Here, we identified sixteen proteins including Gc
      globulin (GC) in urine from bladder cancer patients and normal controls by two
      dimensional fluorescent differential gel electrophoresis (2D-DIGE) and matrix
      assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF MS).
      Bioinformatics analyses indicated GC played important roles in the regulation of
      growth, apoptosis, death and epidermal growth factor receptor activity. The GC
      expression patterns in urine or tissue from cases and controls were further
      quantified by western blotting, immunohistochemical staining and enzyme-linked
      immunosorbent assay (ELISA). ELISA quantification by correcting for creatinine
      expression showed GC-Cr was significantly increased in bladder cancer patients
      than in benign bladder damages cases and normal controls (1013.70+/-851.25 versus
      99.34+/-55.87, 105.32+/-47.81 ng/mg, respectively). Receiver operating
      characteristic (ROC) analysis suggested that at 161.086 ng/mg urinary GC, bladder
      cancer could be detected with 92.31% sensitivity and 83.02% specificity, and
      1407.481 ng/mg with 82.61% sensitivity and 88.24% specificity could be used for
      the detection of infiltrating urothelial carcinoma of bladder cancer. Taken
      together, we identified GC as a potential novel urinary biomarker for the early
      detection and surveillance of bladder cancer.

PMID- 22986150
TI  - The syndromes of reduced sensitivity to thyroid hormone.
AB  - BACKGROUND: Six known steps are required for the circulating thyroid hormone (TH)
      to exert its action on target tissues. For three of these steps, human mutations
      and distinct phenotypes have been identified. SCOPE OF REVIEW: The clinical,
      laboratory, genetic and molecular characteristics of these three defects of TH
      action are the subject of this review. The first defect, recognized 45years ago,
      produces resistance to TH and carries the acronym, RTH. In the majority of cases
      it is caused by TH receptor beta gene mutations. It has been found in over 3000
      individuals belonging to approximately 1000 families. Two relatively novel
      syndromes presenting reduced sensitivity to TH involve membrane transport and
      metabolism of TH. One of them, caused by mutations in the TH cell-membrane
      transporter MCT8, produces severe psychomotor defects. It has been identified in
      more than 170 males from 90 families. A defect of the intracellular metabolism of
      TH in 10 individuals from 8 families is caused by mutations in the SECISBP2 gene
      required for the synthesis of selenoproteins, including TH deiodinases. MAJOR
      CONCLUSIONS: Defects at different steps along the pathway leading to TH action at
      cellular level can manifest as reduced sensitivity to TH. GENERAL SIGNIFICANCE:
      Knowledge of the molecular mechanisms involved in TH action allows the
      recognition of the phenotypes caused by defects of TH action. Once previously
      known defects have been ruled out, new molecular defects could be sought, thus
      opening the avenue for novel insights in thyroid physiology. This article is part
      of a Special Issue entitled Thyroid hormone signaling.

PMID- 22986153
TI  - Total variation based gradient descent algorithm for sparse-view photoacoustic
      image reconstruction.
AB  - In photoacoustic imaging (PAI), reconstruction from sparse-view sampling data is
      a remaining challenge in the cases of fast or real-time imaging. In this paper,
      we present our study on a total variation based gradient descent (TV-GD)
      algorithm for sparse-view PAI reconstruction. This algorithm involves the total
      variation (TV) method in compressed sensing (CS) theory. The objective function
      of the algorithm is modified by adding the TV value of the reconstructed image.
      With this modification, the reconstructed image could be closer to the real
      optical energy distribution map. Additionally in the proposed algorithm, the
      photoacoustic data is processed and the image is updated individually at each
      detection point. In this way, the calculation with large matrix can be avoided
      and a more frequent image update can be obtained. Through the numerical
      simulations, the proposed algorithm is verified and compared with other
      reconstruction algorithms which have been widely used in PAI. The peak signal-to
      noise ratio (PSNR) of the image reconstructed by this algorithm is higher than
      those by the other algorithms. Additionally, the convergence of the algorithm,
      the robustness to noise and the tunable parameter are further discussed. The TV
      based algorithm is also implemented in the in vitro experiment. The better
      performance of the proposed method is revealed in the experiments results. From
      the results, it is seen that the TV-GD algorithm may be a practical and efficient
      algorithm for sparse-view PAI reconstruction.

PMID- 22986154
TI  - Ultrasonic drive of small mechanical components on a tapered metal strip.
AB  - In this report, we demonstrate that small mechanical components such as bars, bar
      composites, disks and cogwheels, centered at a nodal point of tapered metal strip
      in flexural ultrasonic vibration, can be ultrasonically driven to rotate by the
      tapered metal strip. It is experimentally found that revolution speed of the
      small mechanical components is affected by the metal strip vibration, and the
      structure and size of the small mechanical components. The revolution speed
      increases as the metal strip vibration increases and the size of the small
      mechanical components decreases, and it may be higher than 600rpm. Measuring the
      transient response of angular speed, driving torque on the small disk with 4.7mm
      diameter and 0.1mm thickness is estimated to be 0.91MUNm when the driving voltage
      is 100V(p-p) and the actuator is in resonance. Travelling waves are found around
      the nodal point of the metal strip, which may be the cause of the rotary drive.

PMID- 22986155
TI  - Rotary ultrasonic machining of CFRP composites: a study on power consumption.
AB  - Carbon fiber reinforced plastic (CFRP) composites are very difficult to machine.
      A large number of holes need to be drilled in CFRP for many applications.
      Therefore, it is important to develop cost-effective drilling processes. CFRP has
      been drilled by rotary ultrasonic machining (RUM) successfully. The literature
      has reports about the effects of input variables on output variables (including
      cutting force, torque, surface roughness, tool wear, and workpiece delamination)
      in RUM of CFRP. However, there are no reports on power consumption in RUM of
      CFRP. This paper reports the first study on power consumption in RUM of CFRP. It
      reports an experimental investigation on effects of input variables (ultrasonic
      power, tool rotation speed, feedrate, and type of CFRP) on power consumption of
      each component (including ultrasonic power supply, spindle motor, coolant pump,
      and air compressor) and the entire RUM system.

PMID- 22986156
TI  - Staphylococcus aureus infections in the early period after lung transplantation:
      epidemiology, risk factors, and outcomes.
AB  - BACKGROUND: Staphylococcus aureus infections among lung transplant recipients are
      poorly studied. METHODS: We conducted a 5-year retrospective study of the
      epidemiology, clinical manifestations, risk factors, and outcomes of patients
      infected with S aureus within the first 90 days after lung transplantation.
      RESULTS: An S aureus infection developed in 109 of 596 lung transplant (18%)
      recipients. Methicillin-susceptible S aureus (MSSA; 62%) was more common than
      methicillin-resistant S aureus (MRSA; 38%); however, the proportion of infections
      caused by MRSA increased over time. Pneumonia (48%) was the most common
      infection, followed by tracheobronchitis (26%), bacteremia (12%), intrathoracic
      infections (7%), and skin/soft tissue infections (7%). Risk factors included
      mechanical ventilation for > 5 days and isolation of S aureus from recipients'
      sterility cultures. Patients with MRSA cultured from the nares or respiratory
      tract at the time of transplant were at an increased risk for MRSA infection (p <
      0.0001 and p = 0.02, respectively). Infected patients required longer hospital
      and intensive care unit stays (p < 0.0001 for both), but the 30- and 90-day
      mortality rates from the onset of infection were only 7% and 12%, respectively.
      However, infected patients had higher rates of acute and chronic rejection at 1
      (p = 0.048) and 3 years (p = 0.002), and higher rates of mortality at 1 (p =
      0.058) and 3 years (p = 0.009). CONCLUSIONS: S aureus infections within the first
      90 days of lung transplant were associated with low short-term mortality but
      increased long-term rates of mortality and acute and chronic rejection. Future
      studies are needed to explore the utility of S aureus eradication strategies in
      reducing disease burden and improving outcomes.

PMID- 22986157
TI  - Laparoscopic repair of congenital diaphragmatic hernia complicated with sliding
      hiatal hernia with reflux in adult.
AB  - INTRODUCTION: Congenital diaphragmatic hernia (CDH) in adults is a relatively
      rare condition being asymptomatic in the majority of cases. Symptomatic CDH
      should prompt surgical management because they may lead to intestinal obstruction
      or severe pulmonary disease. This is the first reported case of a symptomatic CDH
      complicated with sliding hiatal hernia (SHH). PRESENTATION OF CASE: A 65 years
      old women with reflux and dysphagia was complaining of postprandial paroxysmal
      dyspnea and epigastric pain radiating to her back. Upper endoscopy diagnosed
      sliding and para-esophageal diaphragmatic hernia with severe esophagitis.
      Computed tomography-scan revealed a large Bochdalek hernia at the left diaphragm.
      DISCUSSION: Diagnostic laparoscopy was decided, which confirmed the SHH, but also
      revealed a CDH defect at the tendonous part of the left diaphragm. The left
      bundle of the right crus was intact, separating the two hernia components
      (sliding and congenital). Extensive adhesiolysis was performed, dissecting and
      separating the stomach away from the diaphragm. Posterior cruroplasty at the
      esophageal hiatus was performed for the SHH with Nissen fundoplication as
      antireflux procedure. Primary continuous suture repair was performed for the CDH,
      reinforced with prosthetic mesh on top. Operative time was 150min with no
      morbidity. The patient was discharged home uneventfully the third postoperative
      day. On 12-months follow-up, she reported no symptoms and improvement in quality
      of life. CONCLUSION: Laparoscopy is a unique method for a precise diagnosis of
      symptomatic congenital diaphragmatic hernia in adults being also a safe and
      viable technique for a successful repair at the same time. Experience of advanced
      laparoscopic surgery is required.

PMID- 22986158
TI  - Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the
      spinal cord and urinary bladder of rats with spinal cord injury.
AB  - Spinal cord injury (SCI) leads to an inflammatory response that generates
      substantial secondary damage within the tissue besides the primary damage.
      Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid
      metabolism that are involved in the mediation of various inflammatory disorders
      including SCI. In this study, we investigated the possible protective effects of
      montelukast, a leukotriene receptor blocker, on SCI-induced oxidative damage.
      Wistar albino rats (n=24) were divided randomly as control, vehicle- or
      montelukast (10mg/kg, ip)-treated SCI groups. To induce SCI, a standard weight
      drop method that induced a moderately severe injury at T10 was used. Vehicle or
      montelukast were administered to the injured animals 15 min after injury. At
      seven days post-injury, neurological examination was performed and rats were
      decapitated. Blood samples were taken to evaluate leukotriene B4 levels, and pro
      inflmamatory cytokines (TNF-alpha, IL-1beta) while in spinal cord and urinary
      bladder samples malondialdehyde (MDA), glutathione (GSH), luminol
      chemiluminescence (CL) levels and myeloperoxidase (MPO) and caspase-3 activities
      were determined. Tissues were also evaluated histologically. SCI caused
      significant decreases in tissue GSH, which were accompanied with significant
      increases in luminol CL and MDA levels and MPO and caspase-3 activities, while
      pro-inflammatory cytokines in the plasma were elevated. On the other hand,
      montelukast treatment reversed these parameters and improved histological
      findings. In conclusion, SCI caused oxidative tissue injury through the
      activation of pro-inflammatory mediators and by neutrophil infiltration into
      tissues, and the neuroprotective and antiapoptotic effects of montelukast are
      mediated by the inhibition of lipid peroxidation, neutrophil accumulation and pro
      inflammatory cytokine release. Moreover, montelukast does not only exert
      antioxidant and antiapoptotic effects on the spinal cord, but it has a
      significant impact on the bladder tissue damage secondary to SCI.

PMID- 22986159
TI  - Thermoregulatory responses elicited by microinjection of L-glutamate and its
      interaction with thermogenic effects of GABA and prostaglandin E2 in the preoptic
      area.
AB  - The aim of the present study was to investigate the thermoregulatory effects of
      neuronal activation with sodium L-glutamate (glutamate) in the preoptic area
      (POA) of the hypothalamus and to examine its possible interaction with the
      thermogenic effects of GABA and prostaglandin E(2) (PGE(2)). Unilateral
      microinjection of glutamate (5 nmol) into the lateral POA or its vicinity
      elicited a prompt increase in tail skin temperature and simultaneous decreases in
      the O(2) consumption rate (VO(2)), heart rate, and colonic temperature in
      urethane-chloralose-anesthetized rats. A central subpopulation of these sites at
      around the level of bregma was also responsive to the thermogenic and tachycardic
      effects of GABA (30 nmol). Although the microinjection of GABA into nearby sites
      elicited no direct effect, it greatly attenuated the hypothermic effects of
      glutamate subsequently administered to the same site. These results suggest that
      activation of the lateral POA elicited heat-loss responses and that its central
      part provided a tonic inhibitory drive toward heat production and tail
      vasoconstriction. On the other hand, the microinjection of glutamate elicited
      initial small decreases and subsequent large increases in VO(2) and heart rate in
      the rostromedial POA. However, no thermoregulatory response was elicited by the
      microinjection of glutamate at sites where the microinjection of PGE(2) (35 fmol)
      elicited thermogenic, tachycardic and hyperthermic responses. These results may
      suggest that the rostromedial POA contained two glutamate-responsive cell groups
      that had opposite influences on thermoregulation and that the locus that was
      highly sensitive to the thermogenic effect of PGE(2) was unreactive to glutamate.
      Collectively, activation of neurons in the lateral POA and rostromedial POA
      evoked distinct thermoregulatory responses.

PMID- 22986160
TI  - Peri-infarct flow transients predict outcome in rat focal brain ischemia.
AB  - Spreading depolarizations are accompanied by transient changes in cerebral blood
      flow (CBF). In a post hoc analysis of previously studied control rats we analyzed
      CBF time courses after middle cerebral artery occlusion in the rat in order to
      test whether intra-ischemic flow, reperfusion, and different parameters of peri
      infarct flow transients (PIFTs) (amplitude, number) can predict outcome. Sprague
      Dawley rats anesthetized with either halothane (n=23) or isoflurane (n=32)
      underwent 90-min filament occlusion of the middle cerebral artery followed by 72
      h of reperfusion. The infarct size was determined by 2,3,5-triphenyltetrazolium
      chloride staining. Relative CBF changes were monitored by laser Doppler flowmetry
      at 4-5 mm lateral, and 1-2mm posterior to Bregma. An additional filament
      occlusion study (n=12) was performed to validate that PIFTs were coupled to
      direct current shifts of spreading depolarization. The PIFT-direct current shift
      study revealed that every PIFT was associated with a negative direct current
      shift typical of spreading depolarization. Post-hoc analysis showed that the
      number of PIFTs, especially with the combination of intra-ischemic level of flow,
      can predict the development of cortical infarcts. These findings show that PIFTs
      can serve as an early biomarker in predicting outcome in preclinical animal
      studies.

PMID- 22986161
TI  - Bryostatin-1 promotes long-term potentiation via activation of PKCalpha and
      PKCepsilon in the hippocampus.
AB  - Activation of protein kinase C (PKC) by bryostatin-1 affects various functions of
      the central nervous system. We explored whether bryostatin-1 influenced synaptic
      plasticity via a process involving PKC. Our purpose was to examine whether
      bryostatin-1 affected the induction of hippocampal long-term potentiation (LTP)
      in Schaffer-collateral fibers (CA1 fibers) of the hippocampus, and/or influenced
      the intracellular Ca(2+) level of hippocampal neurons. We also determined the PKC
      isoforms involved in these processes. We found that bryostatin-1 strongly
      facilitated LTP induction, in a dose-dependent manner, upon single-theta burst
      stimulation (TBS). Further, intracellular Ca(2+) levels also increased with
      increasing concentration of bryostatin-1. The facilitative effects of bryostatin
      1 in terms of LTP induction and enhancement of intracellular Ca(2+) levels were
      blocked by specific inhibitors of PKCalpha and PKCepsilon, but not of PKCdelta.
      Our results suggest that bryostatin-1 is involved in neuronal functioning and
      facilitates induction of LTP via activation of PKCalpha and/or PKCepsilon.

PMID- 22986162
TI  - Reduced striatal dopamine D1-D2 receptor heteromer expression and behavioural
      subsensitivity in juvenile rats.
AB  - In adult rat striatum the dopamine D1-D2 receptor heteromer is expressed
      selectively in a subset of medium spiny neurons (MSNs) that coexpress the
      dopamine D1 and D2 receptors (D1R and D2R) as well as dynorphin (DYN) and
      enkephalin (ENK), with higher coexpression in nucleus accumbens (NAc) and much
      lower in the caudate putamen (CP). In the present study we showed that in
      neonatal striatal cultured neurons >90% exhibited the D1R/D2R-DYN/ENK phenotype.
      Similarly, in the striatum of juvenile rats (age 26-28 days) coexpression of D1R
      and D2R was also coincident with the expression of both DYN and ENK.
      Quantification of the number of striatal MSNs exhibiting coexpression of D1R and
      D2R in juvenile rats revealed significantly lower coexpression in NAc shell, but
      not core, and CP than in adult rats. However, within MSNs that coexpressed D1R
      and D2R, the propensity to form the D1-D2 receptor heteromer did not differ
      between age groups. Consistent with reduced coexpression of the D1R and D2R,
      juvenile rats exhibited subsensitivity to D1-D2 receptor heteromer-induced
      grooming following activation by SKF 83959. Given the proposed role of D1R/D2R
      coexpressing MSNs in the regulation of thalamic output, and the recent discovery
      that these MSNs exhibit both inhibitory and excitatory capabilities, these
      findings suggest that the functional regulation of neurotransmission by the
      dopamine D1-D2 receptor heteromer within the juvenile striatum may be
      significantly different than in the adult.

PMID- 22986163
TI  - Repeated restraint stress increases basolateral amygdala neuronal activity in an
      age-dependent manner.
AB  - Chronic stress is a precipitating factor for affective disorders such as
      depression and anxiety. This is associated with the effects of chronic stress on
      the amygdala. Adolescents may be more vulnerable to the effects of chronic
      stress, which may be related to its impact on amygdala function. However, the
      stress-induced changes in amygdala neuronal activity, and the age-dependent
      impact of chronic stress on amygdala neuronal activity have not been studied in
      depth. In this study, we investigated how repeated restraint impacts basolateral
      amygdala (BLA) projection neuron activity in both adolescent and adult rats.
      Using in vivo extracellular recordings from anesthetized rats, we found that
      repeated restraint increased the number of spontaneously firing neurons in the
      BLA of adolescent rats, but did not significantly increase the firing rate. In
      contrast, repeated restraint increased the firing rate of BLA neurons in adult
      rats, but did not change the number of spontaneously firing neurons. This is the
      first direct evidence of how stress differently impacts amygdala physiology in
      adolescent and adult rats. These findings may shed light on the mechanism by
      which chronic stress may age-dependently precipitate psychiatric disorders.

PMID- 22986165
TI  - Intercalated and paracapsular cell islands of the adult rat amygdala: a combined
      rapid-Golgi, ultrastructural, and immunohistochemical account.
AB  - The anterior and rostral paracapsular intercalated islands (AIC and PIC,
      respectively) were studied in the context of the amygdaloid modulation of
      fear/anxiety using horizontal sections. The structural analysis carried out using
      silver-impregnated specimens revealed that the AIC is composed of tightly packed,
      medium-sized spiny neurons with distinct dendritic and axonal patterns that send
      projecting axons to the central nucleus of the amygdala. The AIC occupies a
      strategic position between the basolateral amygdaloid complex and the caudal limb
      of the anterior commissure from which it receives fibers en passage and axon
      terminals. Electron microscopic observation of terminal (i.e., synaptic)
      degeneration 72 h after the surgical interruption of the anterior commissure,
      confirms the synaptic interaction between the latter and the AIC neurons. These
      observations suggest that these islands may gate the activity of neurons from the
      contralateral basal forebrain and synchronize the anxiogenic output of both
      amygdalae. Immunohistochemical analysis indicated that, within the AIC and
      rostral PIC, the distance between tyrosine hydroxylase-immunoreactive terminals
      and the punctate dopamine D(1) receptor immunoreactivity, was in the micrometer
      range. These results indicate a short distance and a rapid extrasynaptic form of
      dopamine volume transmission mediated via D(1) receptors in the AIC and PIC which
      may enhance fear and anxiety by suppressing feed-forward inhibition in the
      basolateral and central amygdaloid nuclei. The strong suggestion for a
      commissural axon projection to the AIC documented here, coupled with the previous
      evidences indicting an isocortical and amygdalar contributions to the anterior
      commissure, opens the possibility that the AIC may be involved in decoding nerve
      impulses arising from both the ipsi- and contra-lateral forebrain to, in turn,
      modulate the homolateral amygdala.

PMID- 22986164
TI  - Immunological regulation of neurogenic niches in the adult brain.
AB  - In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur
      in the adult brain throughout life. The subventricular zone (SVZ) and subgranular
      zone (SGZ) are the main neurogenic regions in the adult brain. Therein, resides a
      subpopulation of astrocytes that act as neural stem cells (NSCs). Increasing
      evidence indicates that pro-inflammatory and other immunological mediators are
      important regulators of neural precursors into the SVZ and the SGZ. There are a
      number of inflammatory cytokines that regulate the function of NSCs. Some of the
      most studied include: interleukin-1, interleukin-6, tumor necrosis factor alpha,
      insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia
      inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon
      gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha.
      This plethora of immunological mediators can control the migration,
      proliferation, quiescence, cell-fate choices and survival of NSCs and their
      progeny. Thus, systemic or local inflammatory processes represent important
      regulators of germinal niches in the adult brain. In this review, we summarized
      the current evidence regarding the effects of pro-inflammatory cytokines involved
      in the regulation of adult NSCs under in vitro and in vivo conditions.
      Additionally, we described the role of proinflammatory cytokines in
      neurodegenerative diseases and some therapeutical approaches for the
      immunomodulation of neural progenitor cells.

PMID- 22986166
TI  - Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental
      area: interaction of GABA(B) and D2 receptors.
AB  - Neurons of the ventral tegmental area (VTA) are critical in the rewarding and
      reinforcing properties of drugs of abuse. Desensitization of VTA neurons to
      moderate extracellular concentrations of dopamine (DA) is dependent on protein
      kinase C (PKC) and intracellular calcium levels. This desensitization is called
      DA inhibition reversal, as it requires concurrent activation of D2 and D1-like
      receptors; activation of D2 receptors alone does not result in desensitization.
      Activation of other G-protein-linked receptors can substitute for D1 activation.
      Like D2 receptors, GABA(B) receptors in the VTA are coupled to G-protein-linked
      potassium channels. In the present study, we examined interactions between a
      GABA(B) agonist, baclofen, and dopamine agonists, dopamine and quinpirole, to
      determine whether there was some interaction in the processes of desensitization
      of GABA(B) and D2 responses. Long-duration administration of baclofen alone
      produced reversal of the baclofen-induced inhibition indicative of
      desensitization, and this desensitization persisted for at least 60 min after
      baclofen washout. Desensitization to baclofen was dependent on PKC. Dopamine
      inhibition was reduced for 30 min after baclofen-induced desensitization and
      conversely, the magnitude of baclofen inhibition was reduced for 30 min by long
      duration application of dopamine, but not quinpirole. These results indicate that
      D2 and GABA(B) receptors share some PKC-dependent mechanisms of receptor
      desensitization.

PMID- 22986167
TI  - Adolescent binge drinking increases expression of the danger signal receptor
      agonist HMGB1 and Toll-like receptors in the adult prefrontal cortex.
AB  - Adolescence is a critical developmental stage of life during which the prefrontal
      cortex (PFC) matures, and binge drinking and alcohol abuse are common. Recent
      studies have found that ethanol increases neuroinflammation via upregulated high
      mobility group box 1 (HMGB1) signaling through Toll-like receptors (TLRs).
      HMGB1/TLR 'danger signaling' induces multiple brain innate immune genes that
      could alter brain function. To determine whether adolescent binge drinking
      persistently increases innate immune gene expression in the PFC, rats (P25-P55)
      were exposed to adolescent intermittent ethanol (AIE [5.0 g/kg, 2-day on/2-day
      off schedule]). On P56, HMGB1/TLR danger signaling was assessed using
      immunohistochemistry (i.e., +immunoreactivity [+IR]). In a separate group of
      subjects, spatial and reversal learning on the Barnes maze was assessed in early
      adulthood (P64-P75), and HMGB1/TLR danger signaling was measured using
      immunohistochemistry for +IR and RT-PCR for mRNA in adulthood (P80).
      Immunohistochemical assessment at P56 and 24 days later at P80 revealed increased
      frontal cortical HMGB1, TLR4, and TLR3 in the AIE-treated rats. Adolescent
      intermittent ethanol treatment did not alter adult spatial learning on the Barnes
      maze, but did cause reversal learning deficits and increased perseverative
      behavior. Barnes maze deficits correlated with the expression of danger signal
      receptors in the PFC. Taken together, these findings provide evidence that
      adolescent binge drinking leads to persistent upregulation of innate immune
      danger signaling in the adult PFC that correlates with adult neurocognitive
      dysfunction.

PMID- 22986168
TI  - Transcriptional expression patterns triggered by chemically distinct
      neuroprotective molecules.
AB  - Glutamate-mediated excitotoxicity has been purported to underlie many
      neurodegenerative disorders. A subtype of glutamate receptors, namely N-methyl-d
      aspartate (NMDA) receptors, has been recognized as potential targets for
      neuroprotection. To increase our understanding of the mechanisms that underlie
      this neuroprotection, we employed a mouse model of glutamate receptor-induced
      excitotoxic injury. Primary cortical neurons derived from postnatal day-0 CD-1
      mice were cultured in the presence or absence of neuroprotective molecules and
      exposed to NMDA. Following a recovery period, whole genome expression was
      measured by microarray analysis. We used a combination of database and text
      mining, as well as systems modeling to identify signatures within the
      differentially expressed genes. While molecules differed in their mechanisms of
      action, we found significant overlap in the expression of a core group of genes
      and pathways. Many of these molecules have clear links to neuronal protection and
      survival, including ion channels, transporters, as well as signaling pathways
      including the mitogen-activated protein kinase (MAPK), the Toll-like receptor
      (TLR), and the hypoxic inducible factor (HIF). Within the TLR pathway, we also
      discovered a significant enrichment of interferon regulatory factor 7 (IRF7)
      regulated genes. Knockdown of Irf7 by RNA interference resulted in reduced
      survival following NMDA treatment. Given the prominent role that IRF7 plays in
      the transduction of type-I interferons (IFNs), we also tested whether type-I IFNs
      alone functioned as neuroprotective agents and found that type-I IFNs were
      sufficient to promote neuronal survival. Our data suggest that the TLR/IRF7/IFN
      axis plays a significant role in recovery from glutamate-induced excitotoxicity.

PMID- 22986169
TI  - Disruption of circadian rhythmicity and suprachiasmatic action potential
      frequency in a mouse model with constitutive activation of glycogen synthase
      kinase 3.
AB  - Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been
      implicated in psychiatric diseases, neurodevelopment, and circadian regulation.
      Both GSK3 isoforms, alpha and beta, exhibit a 24-h variation of inhibitory
      phosphorylation within the suprachiasmatic nucleus (SCN), the primary circadian
      pacemaker. We examined the hypothesis that rhythmic GSK3 activity is critical for
      robust circadian rhythmicity using GSK3alpha(21A/21A)/beta(9A/9A) knock-in mice
      with serine-alanine substitutions at the inhibitory phosphorylation sites, making
      both forms constitutively active. We monitored wheel-running locomotor activity
      of GSK3 knock-in mice and used loose-patch electrophysiology to examine the
      effect of chronic GSK3 activity on circadian behavior and SCN neuronal activity.
      Double transgenic GSK3alpha/beta knock-in mice exhibit disrupted behavioral
      rhythmicity, including significantly decreased rhythmic amplitude, lengthened
      active period, and increased activity bouts per day. This behavioral disruption
      was dependent on chronic activation of both GSK3 isoforms and was not seen in
      single transgenic GSK3alpha or GSK3beta knock-in mice. Underlying the behavioral
      changes, SCN neurons from double transgenic GSK3alpha/beta knock-in mice
      exhibited significantly higher spike rates during the subjective night compared
      to those from wild-type controls, with no differences detected during the
      subjective day. These results suggest that constitutive activation of GSK3
      results in the loss of the typical day/night variation of SCN neuronal activity.
      Together, these results implicate GSK3 activity as a critical regulator of
      circadian behavior and neurophysiological rhythms. Because GSK3 has been
      implicated in numerous pathologies, understanding how GSK3 modulates circadian
      rhythms and neurophysiological activity may lead to novel therapeutics for
      pathological disorders and circadian rhythm dysfunction.

PMID- 22986170
TI  - Spontaneous activity in the developing gerbil auditory cortex in vivo involves
      GABAergic transmission.
AB  - A salient feature of the developing brain is that spontaneous oscillations (SOs)
      and waves may influence the emergence of synaptic connections. While GABA
      produces depolarization and may support SOs in the neurons of developing rodents,
      it elicits hyperpolarization and diminishes SOs in developing gerbil auditory
      cortex (ACx). Therefore, we asked whether SOs exist in developing gerbil ACx in
      vivo and if GABAergic involvement can be manipulated. In vivo extracellular
      recordings in P3-5 ACx revealed SOs with longer burst durations and shorter inter
      event intervals compared to ACx SOs in slices. ACx was then validated by gross
      anatomical features and lesions created at the in vivo recording site that
      corresponded with the electrophysiological coordinates of thalamorecipient ACx in
      slices. Further, NeuroVue Red, a lipophilic dye loaded at the in vivo recording
      sites, stained anatomically identifiable fiber tracks between the ACx and the
      auditory thalamus, medial geniculate body (MG). Separately, to chronically
      perturb GABAergic role in SOs, P2-5 pups were administered daily with GABA(A)
      receptor blocker, bicuculline (BIC). We then recorded from P14-17 ACx neurons in
      slices generated after hearing onset. ACx neurons from BIC-administered pups
      exhibited spontaneous action potentials in contrast to subthreshold synaptic
      potentials in neurons from sham-injected animals. Finally, to elucidate whether
      the gap junction blocker mefloquine (MFQ) previously shown to dampen ACx SOs in
      slices affected GABAergic transmission, MFQ was acutely applied in P3-5 slices
      while spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded.
      Whereas MFQ increased the amplitude and frequency of sIPSCs in ACx neurons, the
      broad-spectrum gap junction blocker carbenoxolone decreased sIPSC amplitudes
      only. Together, we show that P2-5 gerbil ACx can endogenously generate SOs in
      vivo. Persistence of activity in ACx in P14-17 slices from pups administered with
      BIC at P2-5 implies that inhibitory GABAergic activity linked with gap-junction
      participates in the maturation of ACx.

PMID- 22986171
TI  - Gastric acid secretion induced by paraventricular nucleus microinjection of
      orexin A is mediated through activation of neuropeptide Yergic system.
AB  - Very recently, we have reported that the modulatory effect of PVN on gastric acid
      secretion may be mediated through the orexin fibers and/or orexin-responsive
      neurons. In this study, we address the hypothesis which demonstrates the
      existence of a putative orexin A - neuropeptide Y Y1/Y5 receptors interaction to
      increase gastric acid secretion in pyloric-ligated conscious rats. Male Wistar
      rats were implanted with guide canula directed to the PVN and lateral ventricle.
      Intracerebroventricular (ICV) microinjections of GR-231118 (Y1 receptor
      antagonist) and CGP-71683 (Y5 receptor antagonist) on gastric acid secretion were
      considered. The effect of pretreatment with Y1 receptor antagonist, GR-231118,
      and Y5 receptor antagonist, CGP-71683, on PVN orexin A-induced acid secretion was
      assessed. Gastric acid secretion was measured using the pylorus-ligation method,
      and the amount of gastric acid was determined by titration with 0.01N NaOH to a
      pH of 7.0. KEY RESULTS: ICV microinjections of GR-231118 and CGP-71683 decreased
      acid secretion by 25+/-0.05% and 67+/-0.02%, respectively. ICV microinjections of
      GR-231118 and CGP-71683 inhibited effects of PVN-injected orexin-A on acid
      secretion. We suggest that Y1 and Y5 receptors stimulate gastric acid secretion
      and the stimulatory effect of PVN orexin receptors on gastric acid secretion may
      be mediated via interactions, at least in part, through activation of Y1 and Y5
      receptors. These neural pathways may play key roles in the orexinergic action of
      orexins in the cephalic phase of gastric acid secretion.

PMID- 22986173
TI  - Exploration of the attitudes of nursing students to peer physical examination and
      physical examination of patients.
AB  - BACKGROUND: The use of peer physical examination (PPE) in early clinical skills
      has been studied amongst medical students. The majority of students are
      comfortable with using peer physical examination, when sensitive areas are
      excluded. Students' attitudes are related to their personal characteristics:
      gender, age, religious faith, and ethnicity. There is no data on nursing
      students' attitudes to peer physical examination. OBJECTIVES: Identify and
      explore: DESIGN: Dual cohort, cross-sectional, anonymous survey. SETTING: Three
      year undergraduate nursing programme, skills centre and service clinical
      learning. METHODS: All first and third year nursing students were asked to
      complete a modified Examining Fellow Students questionnaire at the end of 2008.
      The questionnaire asked students to indicate which of 12 body areas they would
      not be willing to examine/have examined by a peer of the same/opposite gender.
      This study also asked students which of the 12 body areas they felt uncomfortable
      examining on patients. RESULTS: The response rate was 76% (128/168). The students
      were predominantly female (93% female; 7% male). Most students were comfortable
      with examining non-sensitive body regions of peers (78.2%-100% willing) and
      patients (92.3-100% willing). Male gender was significantly associated with
      willingness to examine and be examined by peers (p=0.001); Asian students were
      significantly less willing to engage in peer physical examination with opposite
      gender (p<0.007). Year 3 students were significantly more comfortable than Year 1
      in examining patients of either gender (p<0.001). DISCUSSION AND CONCLUSIONS: In
      spite of the male gender findings, this predominantly female population expresses
      similar attitudes to the gender-balanced medical student studies - high
      acceptability for non-sensitive areas. The role of characteristics and attitudes
      to peer physical examination shows similarities and differences to other studies.
      Student characteristics were not related to patient examination attitudes.

PMID- 22986174
TI  - Leventhal's common-sense model and medication adherence.

PMID- 22986172
TI  - Ischemia-reperfusion impairs blood-brain barrier function and alters tight
      junction protein expression in the ovine fetus.
AB  - The blood-brain barrier is a restrictive interface between the brain parenchyma
      and the intravascular compartment. Tight junctions contribute to the integrity of
      the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could
      be an important component of fetal brain injury. We hypothesized that increases
      in blood-brain barrier permeability after ischemia depend upon the duration of
      reperfusion and that decreases in tight junction proteins are associated with the
      ischemia-related impairment in blood-brain barrier function in the fetus. Blood
      brain barrier function was quantified with the blood-to-brain transfer constant
      (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127
      days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The
      largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5
      expressions decreased at 4 h, but returned toward control levels 24 and 48 h
      after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse
      correlations between K(i) and tight junction proteins suggest that the decreases
      in tight junction proteins contribute to impaired blood-brain barrier function
      after ischemia. We conclude that impaired blood-brain barrier function is an
      important component of hypoxic-ischemic brain injury in the fetus, and that
      increases in quantitatively measured barrier permeability (K(i)) change as a
      function of the duration of reperfusion after ischemia. The largest increase in
      permeability occurs 4 h after ischemia and blood-brain barrier function improves
      early after injury because the blood-brain barrier is less permeable 24 and 48
      than 4 h after ischemia. Changes in the tight junction molecular composition are
      associated with increases in blood-brain barrier permeability after ischemia.

PMID- 22986175
TI  - Showing the way: enhance the value of research findings.

PMID- 22986176
TI  - A review of published studies of patients' illness perceptions and medication
      adherence: lessons learned and future directions.
AB  - BACKGROUND: Patients who seek medical care and who are prescribed medication may
      choose to either accept or not accept the prescriber's recommendations to use the
      prescribed medication. The Common Sense Model (CSM) is one behavioral model that
      can help researchers and practitioners to identify patients' illness perceptions
      that drive their decisions. OBJECTIVE: This article reviews published research
      that evaluated the impact of illness representations (as defined in CSM) with
      medication adherence. METHODS: A narrative review of published research in
      illness representation and medication adherence was conducted. Articles were
      searched using MEDLINE, PreMEDLINE, evidence-based medicine reviews, and the
      International Pharmaceutical Abstracts databases and using the search terms
      medication adherence, compliance, illness perception, self-regulation theory, and
      common-sense model. RESULTS: Eleven published studies were identified that
      compared illness representation (or illness perception) and medication adherence.
      Each illness representation factor, with the exception of illness coherence,
      directly or indirectly impacted medication adherence. Illness identity, where
      symptoms are used to label a health condition, can impact medication adherence,
      even with asymptomatic conditions such as hypertension. Patient age, disease
      condition, and culture may impact patient response to illness perceptions.
      Recommendations for future research are to (1) use longitudinal studies to
      evaluate the cause-effect relationships between illness perceptions and
      medication adherence, (2) study patients' early experiences with their illness,
      (3) recruit patients who are nonadherent, (4) use clinical outcome measures in
      addition to the self-report medication adherence measures, and (5) include
      patient age and culture in the model. CONCLUSIONS: Although the CSM is a well
      known patient behavior model, its use to explain medication adherence has been
      limited to cross-sectional studies across various health conditions. Further
      research is needed to elucidate the relationships between illness perceptions and
      patient medication adherence, which can help practitioners to better engage and
      communicate with patients.

PMID- 22986177
TI  - Mimicry and play initiation in 18-month-old infants.
AB  - Across two experiments, we examined the relationship between 18-month-old
      infants' mimicry and social behavior - particularly invitations to play with an
      adult play partner. In Experiment 1, we manipulated whether an adult mimicked the
      infant's play or not during an initial play phase. We found that infants who had
      been mimicked were subsequently more likely to invite the adult to join their
      play with a new toy. In addition, they reenacted marginally more steps from a
      social learning demonstration she gave. In Experiment 2, infants had the chance
      to spontaneously mimic the adult during the play phase. Complementing Experiment
      1, those infants who spent more time mimicking the adult were more likely to
      invite her to play with a new toy. This effect was specific to play and not
      apparent in other communicative acts, such as directing the adult's attention to
      an event or requesting toys. Together, the results suggest that infants use
      mimicry as a tool to establish social connections with others and that mimicry
      has specific influences on social behaviors related to initiating subsequent
      joint interactions.

PMID- 22986178
TI  - Adoption as an intervention for institutionally reared children: HPA functioning
      and developmental status.
AB  - Institutional care, particularly when experienced early in life, is associated
      with delays in social and emotional development that often persist years after
      adoption. It has been hypothesized that compromise of the hypothalamic-pituitary
      adrenocortical (HPA) axis due to adverse condition in institutions is a mediator
      of later emotional and behavioral problems. The first goal of our project was to
      investigate whether improvements in the social and emotional environment are
      associated with changes in HPA axis function. The second goal was to explore
      whether HPA alterations related to early social adversity were associated with
      more compromised general development and social and emotional functioning post
      adoption. Children adopted from Eastern European orphanages (N = 76, mean age was
      17 months, SD = 5) were followed as part of an ongoing longitudinal study. Data,
      including diurnal cortisol patterns, were collected at two time points: baseline
      (within one month of adoption) and follow-up (six months later). Cortisol values
      were averaged over two days of saliva sampling after wake-up and before bedtime.
      We found that morning cortisol values increased between the baseline assessment
      (M = 0.27 MUg/dl, SD = 0.13) and follow-up (M = 0.33 MUg/dl, SD = 0.20), t(76) = 
      2.1, p<0.05. HPA functioning was not associated with general developmental level
      at either the initial or six months post-adoption assessments. However,
      dysregulation of the HPA axis (i.e., flatter diurnal pattern) at follow-up was
      associated with more behavioral and emotional problems. Overall, these results
      suggest that investigating specific physiological mechanisms is important in
      identifying children at risk for persistent social and emotional problems and in
      understanding the long-term consequences of early adversity. Future work should
      investigate whether disturbance in the HPA system is a heightened risk for long
      term negative developmental outcomes.

PMID- 22986179
TI  - Association of IL-10, IL-4, and IL-28B gene polymorphisms with spontaneous
      clearance of hepatitis C virus in a population from Rio de Janeiro.
AB  - BACKGROUND: Cytokines play an important role in the regulation of the immune
      response. In hepatitis C virus (HCV) infection, cytokine levels may influence the
      outcome of acute HCV infection. Polymorphisms in cytokine genes have been
      associated to different expression levels in response to infection. This study
      was carried out to investigate the association of several cytokine gene
      polymorphisms with disease outcome in HCV-infected patients. FINDINGS: Patients
      with chronic or spontaneously resolved HCV infection were included in a cross
      sectional study. A comparative analysis was performed between the groups
      regarding frequency distribution of the following cytokines' gene polymorphisms:
      IL-10 (-1082 A/G; -819 T/C; -592 A/C), IL-4 (+33C/T), IFN-gamma (+874 T/A), TNF
      alpha (-238 G/A and -308 G/A) and IL-28B (rs12979860 C/T and rs8099917 T/G).
      RESULTS: Eighteen patients with spontaneous viral clearance and 161 with chronic
      HCV infection were included. In the comparative analysis, the GG genotype of the
      IL-10 polymorphism -1082A/G was more frequent in patients with spontaneous viral
      clearance when compared to patients with chronic HCV (41.2% vs 6.2%; p = 0.001).
      This association was also found for the CC genotype of the IL-4 polymorphism
      +33C/T (72.2% vs 36.7%; p = 0.017) and the CC and TT genotypes of the IL-28B
      polymorphisms rs 12979860 and rs 8099917 (88.9% vs 30.3%; p < 0.001 and 88.9% vs
      49.6%; p = 0.002). The IL10 (A-1082 G) and IL-28B (Crs12979860T) gene
      polymorphisms showed odds ratios of 12.848 and 11.077, respectively, and thus may
      have a greater influence on HCV spontaneous viral clearance. The IFN-gamma (+874
      T/A), TNF-alpha (-238 G/A and -308 G/A) polymorphisms did not show significant
      association with spontaneous viral clearance or chronicity. CONCLUSION: The G
      allele for IL-10 (-1082 A/G), the C allele for IL-4 (+3 C/T) and the C and T
      alleles for IL-28B (rs12979860 and rs8099917, respectively) are associated with
      spontaneous viral clearance in hepatitis C infection.

PMID- 22986180
TI  - Implication of Arg213 and Arg337 on the kinetic and structural stability of
      firefly luciferase.
AB  - Possible roles of two different Arginine (Arg; R) 213 and 337 on kinetic and
      structural stability of Photinus pyralis luciferase have been investigated using
      thermal and chemical denaturation studies. This enzyme is highly sensitive to
      protease digestion and temperature, which limits its fieldability, particularly
      for in vivo imaging. In order to generate more stable luciferases against trypsin
      digestion, site-directed mutagenesis was conducted to block two representative
      tryptic sites on the surface of N-terminal domain, via substitution of Arg213 and
      Arg337 by methionine (Met; M) and glutamine (Gln; Q), respectively [A. Riahi
      Madvar, S. Hosseinkhani, Protein engineering, design and selection 22 (2009) 655
      663]. The improvement of mutant enzymes stability against protease hydrolysis may
      be attributed to the more rigidity of the enzyme structure upon mutations, as can
      be deducted from elevated levels of m(U-N) values and decrease of activation
      energy. Furthermore, mutation at position 337 which is accompanied with more
      alteration on the basic kinetic properties relative to mutation at position 213,
      revealed the high values of the DeltaG(H(2)O), half-time of inactivation at 30
      degrees C and T(m) for R337Q where Arg213 is maintained in structure. Based on
      the results, it can be concluded that whilst Arg213 affects structural stability,
      Arg337 is critical for kinetic stability.

PMID- 22986181
TI  - Characterization of sugar beet pectic-derived oligosaccharides obtained by
      enzymatic hydrolysis.
AB  - Three pectic oligosaccharides (POS) obtained by enzymatic hydrolysis of sugar
      beet pectin by combining endopolygalacturonase and pectinmethylesterase, were
      characterized using high performance liquid chromatography, thermogravimetric
      analysis, Fourier transform infrared spectroscopy, differential scanning
      calorimetry and X-ray diffraction. According to chromatographic analyses, POS are
      composed of mixture of polymers with different molecular weights and different
      galacturonic acid contents. The thermal analysis showed no major variation in
      thermal behavior regarding POS composition but showed that POS were more
      sensitive to thermal degradation than the parent pectin as well as the
      deesterified pectin. No change in composition of the gaseous products was
      obtained through TGA-FTIR analysis. The X-ray pattern of POS clearly indicated a
      considerable decrease in crystallinity when compared to the native pectin. Thus,
      thermal characterization of POS may have practical repercussions if the
      formulation in which POS is incorporated is submitted to a high temperature
      treatment.

PMID- 22986182
TI  - Dietary Nrf2 activators inhibit atherogenic processes.
AB  - Dietary Nrf2 activators increase expression of phase 2 protein genes in cells
      undergoing oxidative stress resulting in a lowering of oxidative stress.
      Oxidative stress promotes atherogenic processes through oxidizing low density
      lipoproteins and promotion of inflammation through activation of nuclear factor
      kappa B and activation of mitogen-activated protein kinases. Nrf2 activators by
      decreasing oxidative stress decrease the probability of developing
      atherosclerotic lesions.

PMID- 22986183
TI  - LDL oxidative modification and carotid atherosclerosis: results of a multicenter
      study.
AB  - OBJECTIVE: Serum LDL conjugated diene concentration is a marker of oxidative
      modification of LDL. We investigated the relationship between LDL conjugated
      dienes and cross-sectional subclinical atherosclerosis assessed by carotid IMT in
      high-risk subjects of a multicenter study. METHODS: Serum LDL conjugated dienes
      and ultrasonographically assessed carotid intima-media thickness (IMT(mean),
      IMT(max) and IMT(mean-max)) were available for 553 subjects from Finland, France,
      Italy, the Netherlands, and Sweden. RESULTS: In multivariate regression analysis,
      gender (p < 0.001), age (p < 0.001), systolic blood pressure (IMT(mean), p =
      0.01; IMT(mean-max), p = 0.05) and serum LDL conjugated dienes (p = 0.02 for both
      IMT(mean) and IMT(mean-max)) were the strongest determinants of IMT variation,
      adjusted for study center, ultrasound videotape reader and serum LDL cholesterol.
      Pack-years of smoking, added into the regression model, did not destroy the
      significant association between increased serum LDL conjugated dienes and IMT.
      Ratio of LDL conjugated dienes to LDL particle cholesterol was higher in subjects
      of Northern recruiting centers than of Southern centers (r = 0.39, p < 0.0001).
      CONCLUSIONS: There was a cross-sectional association between in vivo increased
      LDL oxidative modification and subclinical atherosclerosis after adjustment for
      traditional risk factors. The subjects in Northern countries of Europe had more
      oxidatively modified lipids per cholesterol in LDL particle than subjects in
      Southern countries.

PMID- 22986184
TI  - Serotypes and virulotypes of non-O157 shiga-toxin producing Escherichia coli
      (STEC) on bovine hides and carcasses.
AB  - Four hundred and fifty beef animal hides and a similar number of carcasses were
      screened for STEC in 3 beef abattoirs over a 12 month period using PCR and
      culture based methods. 67% (301/450) of hides and 27% (122/450) of carcasses were
      STEC PCR positive. Forty isolates representing 12 STEC serotypes (O5:H-, O13:H2,
      O26:H11, O33:H11, O55:H11, O113:H4, O128:H8, O136:H12, O138:H48, O150:H2, O168:H8
      and ONT:H11) and 15 serotype-virulotype combinations were identified. This study
      provides much needed non-O157 STEC surveillance data and also provides further
      evidence of bovines as a source of clinically significant STEC as well as
      identifying 3 emerging serotypes O5:H- (eae-beta1), O13:H2 (eae-zeta), and
      O150:H2 (eae-zeta) that should be considered when developing beef testing
      procedures for non-O157 STEC.

PMID- 22986185
TI  - Hydroxycinnamic acid decarboxylase activity of Brettanomyces bruxellensis
      involved in volatile phenol production: relationship with cell viability.
AB  - Brettanomyces bruxellensis populations have been correlated with an increase in
      phenolic off-flavors in wine. The volatile phenols causing the olfactory defect
      result from the successive decarboxylation and reduction of hydroxycinnamic acids
      that are normal components of red wines. The growth of B. bruxellensis is
      preventable by adding sulfur dioxide (SO(2)), with variable effectiveness.
      Moreover, it was hypothesized that SO(2) was responsible for the entry of B.
      bruxellensis into a viable but non-culturable (VBNC) state. The aim of this
      project was to investigate the effects of SO(2) on the remaining enzyme
      activities of B. bruxellensis populations according to their viability and
      cultivability, focusing on the hydroxycinnamate decarboxylase enzyme, the first
      enzyme needed, rather than the metabolites produced. Enzyme activity was
      determined both in cell-free extracts and resting cells after various SO(2)
      treatments in synthetic media. After slight sulfiting (around 50 mg/L total
      SO(2)), the yeasts had lost part of their enzyme activity but not their
      cultivability. At higher doses (at least 75 mg/L total SO(2)) the majority of
      yeasts had lost their cultivability but still retained part of their enzyme
      activity. These results suggested that non culturable cells retained some enzyme
      activity.

PMID- 22986186
TI  - Optimising the number of isolates to be used to estimate growth parameters of
      mycotoxigenic species.
AB  - The aim of the present work was to mathematically assess the minimum number of
      isolates that would lead to equivalent growth parameters estimates to those
      obtained with a high number of strains. The datasets from two previous works on
      30 Aspergillus carbonarius isolates and 62 Penicillium expansum isolates were
      used for this purpose. First, the datasets were used to produce a global
      estimation of growth parameters MU (growth rate, mm/d) and lambda (time to
      visible growth, d) under the different experimental conditions, providing also a
      95% confidence interval. Second, a computational algorithm was developed in order
      to obtain an estimation of the growth parameters that one would obtain using a
      lower number of isolates and/or replicates, using a bootstrap procedure with 5000
      simulations. The result of this algorithm was the probability that the obtained
      estimation falls in the 95% confidence interval previously produced using all
      sample isolates. Third, the algorithm was intensively applied to obtain these
      probabilities for all possible combinations of isolates and replicates. Finally,
      these results were used to determine the minimum number of isolates and
      replicates needed to obtain a reasonable estimation, i.e. inside the confidence
      interval, with a probability of 0.8, 0.9 and 0.95. The results revealed that
      increasing the number of isolates may be more effective than increasing the
      number of replicates, in terms of increasing the probability. In particular, 12
      17 isolates of A. carbonarius led to the same growth parameters as the total 30
      (p = 0.05) or 9 isolates with p = 0.20; by contrast, 25-30 isolates of P.
      expansum led to the same growth parameters as the total 62 (p = 0.05) or 18-21
      isolates with p = 0.20. As far as we know, this is the first study that provides
      a systematic evaluation of the number of isolates and replicates needed when
      designing an experiment involving mycotoxigenic moulds responses to environmental
      factors, and may serve to support decision making in this kind of studies or
      other similar ones.

PMID- 22986187
TI  - Yeast-yeast interactions revealed by aromatic profile analysis of Sauvignon Blanc
      wine fermented by single or co-culture of non-Saccharomyces and Saccharomyces
      yeasts.
AB  - There has been increasing interest in the use of selected non-Saccharomyces
      yeasts in co-culture with Saccharomyces cerevisiae. The main reason is that the
      multistarter fermentation process is thought to simulate indigenous fermentation,
      thus increasing wine aroma complexity while avoiding the risks linked to natural
      fermentation. However, multistarter fermentation is characterised by complex and
      largely unknown interactions between yeasts. Consequently the resulting wine
      quality is rather unpredictable. In order to better understand the interactions
      that take place between non-Saccharomyces and Saccharomyces yeasts during
      alcoholic fermentation, we analysed the volatile profiles of several mono-culture
      and co-cultures. Candida zemplinina, Torulaspora delbrueckii and Metschnikowia
      pulcherrima were used to conduct fermentations either in mono-culture or in co
      culture with S. cerevisiae. Up to 48 volatile compounds belonging to different
      chemical families were quantified. For the first time, we show that C. zemplinina
      is a strong producer of terpenes and lactones. We demonstrate by means of
      multivariate analysis that different interactions exist between the co-cultures
      studied. We observed a synergistic effect on aromatic compound production when M.
      pulcherrima was in co-culture with S. cerevisiae. However a negative interaction
      was observed between C. zemplinina and S. cerevisiae, which resulted in a
      decrease in terpene and lactone content. These interactions are independent of
      biomass production. The aromatic profiles of T. delbrueckii and S. cerevisiae in
      mono-culture and in co-culture are very close, and are biomass-dependent,
      reflecting a neutral interaction. This study reveals that a whole family of
      compounds could be altered by such interactions. These results suggest that the
      entire metabolic pathway is affected by these interactions.

PMID- 22986188
TI  - Genetic diversity, virulence genes and antimicrobial resistance of Salmonella
      Enteritidis isolated from food and humans over a 24-year period in Brazil.
AB  - Salmonellosis is a major health problem worldwide. Serovar Enteritidis has been a
      primary cause of Salmonella outbreaks in many countries. In Brazil, few molecular
      typing studies have been performed. The aims of this study were to molecularly
      type Salmonella Enteritidis strains isolated in Brazil in order to determine the
      genetic relationship between strains of food and human origin, as well as, to
      assess their pathogenic potential and antimicrobial resistance. A total of 128 S.
      Enteritidis strains isolated from human feces (67) and food (61) between 1986 and
      2010 were studied. The genotypic diversity was assessed by ERIC-PCR and PFGE
      using XbaI, the antimicrobial resistance by the disc-diffusion assay and the
      presence of the SPI-1, SPI-2 and pSTV virulence genes assessed by PCR. The ERIC
      PCR results revealed that 112 strains exhibited a similarity of >85.4% and the
      PFGE that 96 strains exhibited a similarity of >80.0%. Almost all strains (97.6%)
      harbored all 13 virulence genes investigated. Thirty-six strains (28.12%) were
      resistant to nalidixic acid. In conclusion, the nalidixic acid resistance
      observed after 1996 is indicative of an increase in the use of this drug. It may
      be suggested that these 128 strains might have descended from a common ancestor
      that differed little over 24 years and has been both contaminating food and
      humans and causing disease for more than two decades in Brazil.

PMID- 22986189
TI  - Molecular characterization of enterotoxigenic and borderline oxacillin resistant
      Staphylococcus strains from ovine milk.
AB  - Staphylococcal enterotoxins (SEs) produced by Staphylococcus spp. are
      superantigens responsible for food-poisoning and are associated to mobile genetic
      elements such as Staphylococcus aureus pathogenicity islands (SaPI). The presence
      of 13 enterotoxin genes (sea, seb, sec, sed, see, seg, seh, sei, sej, sel, sek,
      seq, and tst) was tested in 15 S. aureus and 24 coagulase-negative Staphylococcus
      (CNS) multi-resistant strains isolated from ovine milk in Sardinia. All CNS
      isolates were enterotoxin-negative, whereas co-presence of sec, sel and tst was
      observed in most of the S. aureus strains. One isolate of S. aureus was
      characterized by tst alone. A multiplex PCR assay aimed at discriminating between
      the integrase genes of pathogenicity islands SaPI2, SaPIbov1, and SaPIMW2 was
      developed. We demonstrated that strains harboring sec, sel and tst were
      associated with SaPIbov1, whereas the strain positive for tst was associated with
      SaPI2. Borderline oxacillin resistant S. aureus strains were also detected. RAPD
      analysis of the Staphylococcus strains showed that clonal relationships were
      correlated with pathogenic profiles.

PMID- 22986190
TI  - Investigation of microorganisms involved in biosynthesis of the kefir grain.
AB  - The purpose of this study was to understand the significance of each
      microorganism in grain formation by evaluating their microbial aggregation and
      cell surface properties during co-aggregation of LAB and yeasts together with an
      investigation of biofilm formation. Non-grain forming strains from viili were
      also evaluated as a comparison. Results indicated that the kefir grain strains,
      Lactobacillus kefiranofaciens and Saccharomyces turicensis possess strong auto
      aggregation ability and that Lactobacillus kefiri shows significant biofilm
      formation properties. Significant co-aggregation was noted when S. turicensis and
      kefir LAB strains (Lb. kefiranofaciens and Lb. kefiri) were co-cultured. Most of
      the tested LAB strains are hydrophilic and had a negative charge on their cell
      surface. Only the kefir LAB strains, Lb. kefiranofaciens HL1 and Lb. kefiri HL2,
      possessed very high hydrophobicity and had a positive cell surface charge at pH
      4.2. In contrast, the LAB and yeasts in viili did not show any significant self
      aggregation or biofilm formation. Based on the above results, we propose that
      grain formation begins with the self-aggregation of Lb. kefiranofaciens and S.
      turicensis to form small granules. At this point, the biofilm producer, Lb.
      kefiri, then begins to attach to the surface of granules and co-aggregates with
      other organisms and components in the milk to form the grains. On sub-culturing,
      more organisms attach to the grains resulting in grain growth. When investigated
      by scanning electron microscopy, it was found that short-chain lactobacilli such
      as Lb. kefiri occupy the surface, while long-chain lactobacilli such as Lb.
      kefiranofaciens have aggregated towards the center of the kefir grains. These
      findings agree with the above hypothesis on the formation of grains. Taken
      together, this study demonstrates the importance of cell surface properties
      together with fermentation conditions to the formation of grains in kefir.

PMID- 22986191
TI  - Optimization of homoexopolysaccharide formation by lactobacilli in gluten-free
      sourdoughs.
AB  - Currently hydrocolloids are applied as baking aids in order to enhance the
      quality of gluten-free bread. Microbial exopolysaccharides (EPS) can also have a
      positive impact on gluten-free baked goods. Provided that yields are sufficient,
      in situ produced EPS may enable clean (additive free) labels. Thus, in situ EPS
      optimization was conducted to achieve high amounts of EPS in gluten-free
      sourdoughs. The influence of flours, dough yield, cell counts, sucrose
      concentration and sucrose fed-batch were investigated for Lactobacillus (L.)
      animalis TMW 1.971, Lactobacillus reuteri TMW 1.106 and Lactobacillus curvatus
      TMW 1.624. Maximal yields of 17.93 g EPS kg(-1) flour were obtained with L.
      animalis TMW 1.971 in buckwheat core doughs, 15.69 g EPS kg(-1) with L. reuteri
      TMW 1.106 in quinoa, and 16.28 g EPS kg(-)(1) flour with L. curvatus TMW 1.624 in
      buckwheat sourdoughs. This study evidences that EPS amounts can be manifolded to
      reach effectual levels through optimization and corroborate the application of
      EPS-forming starter cultures as a promising approach to improve gluten-free baked
      goods.

PMID- 22986192
TI  - Formation of lactic acid bacteria-yeasts communities on the olive surface during
      Spanish-style Manzanilla fermentations.
AB  - This work examines the formation of poly-microbial communities adhered to the
      surface of Manzanilla olive fruits processed according to the Spanish style. The
      experimental design consisted of four pilot fermenters inoculated with four
      Lactobacillus pentosus strains, plus another fermenter which was not inoculated
      and fermented spontaneously. Lactic acid bacteria and yeasts were analysed in
      depth on olive epidermis throughout fermentation by plate count, molecular
      techniques and scanning electron microscopy. Data show that in all cases high
      population levels (above 8 log(10) CFU per olive) were reached for both groups of
      microorganisms at the second week of fermentation and that these counts never
      fell below 6 log(10) CFU per olive during the 3 months that fermenters were
      monitored. In situ observation of olive epidermis slices revealed a strong
      aggregation and adhesion between bacteria and yeasts by the formation of a matrix
      which embedded the microorganisms. Geotrichum candidum, Pichia galeiformis and
      Candida sorbosa were the main yeast species isolated from these biofilms at the
      end of fermentation (confirmed by RFLP analysis of the 5.8S-ITS region), while
      molecular characterization of lactobacilli isolates by means of RAPD-PCR with
      primer OPL(5) showed in many cases a high similarity in their banding profiles
      with the inoculated strains. Results obtained in this survey show the importance
      of studying the olive epidermis throughout fermentation, because ultimately,
      olives are ingested by consumers.

PMID- 22986193
TI  - Effect of a non-lethal High Pressure Homogenization treatment on the in vivo
      response of probiotic lactobacilli.
AB  - Low levels of High Pressure of Homogenization (HPH) can be applied directly to
      lactic acid bacteria cells in order to enhance some functional properties. In a
      previous work we observed that a 50 MPa HPH treatment increased Lactobacillus
      paracasei A13 hydrophobicity and resistance to simulated gastric digestion. The
      aim of this work was to assess the in vivo effects of HPH treatment applied to
      probiotic lactobacilli on their interaction capacity with the gut and on their
      ability to induce IgA cell proliferation in mice intestine. BALB/c mice received
      FITC-labelled cultures of strains, previously treated or not (control) at 50 MPa.
      Fluorescently labelled cells were studied in the intestine of animals sacrificed
      10 and 30 min after intragastric intubation. HPH-treated and control cultures of
      each strain were orally administered to mice for 2, 5 or 7 consecutive days. The
      number of IgA-producing cells in the gut was studied by immunohistochemistry. HPH
      treated probiotic lactobacilli modified their interaction with the small
      intestine. HPH-treated cells induced a higher IgA response compared to untreated
      ones, in a strain- and feeding period-dependent way. HPH treatment could increase
      some in vivo functional characteristics of probiotic strains, highlighting the
      potential of this technique for the development of probiotic cultures.

PMID- 22986194
TI  - Characterization of lactic acid bacteria from naturally-fermented Manzanilla
      Alorena green table olives.
AB  - Manzanilla Alorena (or Alorena) table olives are naturally fermented traditional
      green olives with a denomination of protection (DOP). The aim of this study was
      to search for lactic acid bacteria (LAB) with technological properties of
      interest for possible inclusion in a starter or protective culture preparation or
      also as probiotics. A collection of 144 LAB obtained from Alorena green table
      olives naturally-fermented by four small-medium enterprises (SMEs) from Malaga
      (Spain), including lactobacilli (81.94%), leuconostocs (10.42%) and pediococci
      (7.64%) were studied. REP-PCR clustering and further identification of strains by
      sequencing of phes and rpo genes revealed that all lactobacilli from the
      different SMEs were Lactobacillus pentosus. Pediococci were identified as
      Pediococcus parvulus (SME1) and leuconostocs as Leuconostoc pseudomesenteroides
      (SME1 and SME4). Genotyping revealed that strains were not clonally related and
      exhibited a considerable degree of genomic diversity specially for lactobacilli
      and also for leuconostocs. Some strains exhibit useful technological properties
      such as production of antimicrobial substances active against pathogenic bacteria
      such as Listeria monocytogenes, Bacillus cereus, Staphylococcus aureus,
      Streptococcus mutans and Salmonella enterica, utilization of raffinose and
      stachyose, production of bile salt hydrolase, phytase and haeme-dependent
      catalase activities, growth at 10  degrees C and in the presence of 6.5% NaCl,
      good acidifying capacity and also resistance to freezing. However, none of the
      isolates showed protease or amylase activity, and also did not exhibit biogenic
      amine production from histidine, ornithine, cysteine or tyrosine. On the basis of
      data obtained, selected strains with potential traits were tested for their
      survival at low pH and their tolerance to bile salts, and the survival capacity
      demonstrated by some of the analysed strains are encouraging to further study
      their potential as probiotics.

PMID- 22986195
TI  - Control of Listeria monocytogenes and spoilage bacteria on smoked salmon during
      storage at 5  degrees C after X-ray irradiation.
AB  - In this study, smoked salmon fillets were artificially inoculated with Listeria
      monocytogenes (3.7 +/- 0.2 log CFU g(-1)) and treated with X-ray irradiation
      generated by a RS 2400 X-ray machine (Rad Source Technologies Inc.) using doses
      of 0.0, 0.1, 0.5, 1.0, and 2.0 kGy. Unirradiated and irradiated samples were then
      stored at 5  degrees C for 35 days and tested for L. monocytogenes count after 0,
      5, 10, 15, 20, 25, 30, and 35 days. Also, uninoculated-untreated and uninoculated
      treated samples with the lowest and highest X-ray doses (0.1 and 2.0 kGy) were
      stored at 5  degrees C and examined for psychrotrophs and mesophiles counts after
      0, 5, 10, 15, 20, 25, 30, and 35 days. The initial L. monocytogenes population
      (3.7 log CFU g(-1) ) was significantly (p < 0.05) reduced to an undetectable
      level (<1.0 log CFU g(-1)) by treatment with 1.0 kGy X-ray. Treatment with 0.1
      kGy X-ray significantly reduced the initial psychrotrophs and mesophiles counts
      from 5.3 and 3.0 to 3.3 and 2.3, respectively. However, L. monocytogenes,
      psychrotrophs and mesophiles counts were gradually increased during storage.
      Treatment with 2.0 kGy X-ray kept the L. monocytogenes population under
      detectable level until 35 days. Treatment with 2.0 kGy X-ray kept the mesophiles
      and psychrotrophs counts within the acceptable level until 35 days. These results
      revealed that treatment with X-ray irradiation can significantly reduce the risk
      of listeriosis and extend the shelf life of smoked salmon during storage at 5 
      degrees C.

PMID- 22986196
TI  - Occurrence of viable Brachyspira spp. on carcasses of spent laying hens from
      supermarkets.
AB  - Brachyspira spp. are frequent inhabitants of the chicken's intestine and some
      have been associated with enteric disease in humans. We studied contamination
      with Brachyspira spp. of carcasses of spent laying hens as a possible source of
      infections for humans and animals that may eat this meat. Eleven batches of hen
      carcasses, for a total of 110 carcasses, were bought in Belgian supermarkets
      during 2009-2010. Carcass rinse samples were examined for the presence of
      Brachyspira. Brachyspira spp. were cultured from some carcass in all batches.
      Besides presumably non-pathogenic species such as Brachyspira murdochii and
      Brachyspira innocens, the poultry pathogen Brachyspira intermedia and the poultry
      and suspected human pathogen Brachyspira pilosicoli were identified in 7/11 and
      1/11 carcass batches, respectively, at high numbers, as shown using quantitative
      polymerase chain reactions. Multilocus sequence typing (MLST) demonstrated the
      presence of 2 and 13 MLST types of B. pilosicoli and B. intermedia, respectively,
      with all strains belonging to novel MLST types. The findings show that carcasses
      of spent laying hens are commonly contaminated with high numbers of Brachyspira
      spp., including the suspected zoonotic agent B. pilosicoli.

PMID- 22986197
TI  - Comparison of aerial counts at different sites in beef and sheep abattoirs and
      the relationship between aerial and beef carcass contamination.
AB  - The study examined and compared levels of aerial contamination in commercial beef
      and sheep plants at four sites, i.e. lairage, hide/fleece pulling, evisceration
      and chilling. Aerial contamination was determined by impaction and sedimentation
      onto Plate Count Agar to enumerate Total Viable Counts, MacConkey Agar to
      enumerate coliforms and Violate Red Bile Glucose Agar to enumerate
      Enterobacteriaceae. AS I cannot see any difference in the text here - I am not
      sure what the change is?. The levels of aerial contamination were similar at
      equivalent sites in beef and sheep plants, irrespective of the sampling method or
      the type of organisms recovered. Mean log counts recovered on each medium in the
      chillers were generally significantly lower (P < .05) than the corresponding mean
      log numbers recovered at the other three sites. The relationship between
      impaction (air) and sedimentation (surface) counts could be described by the
      surface to air ratio (SAR) which in this study had an R(2) of 0.77. Further
      studies in an experimental plant compared counts recovered from the neck of beef
      carcasses with aerial counts determined by impaction and sedimentation onto agar
      and irradiated meat pieces. A relationship between counts on beef carcasses and
      in the air could not be established, irrespective of the method used to compare
      counts.

PMID- 22986198
TI  - Pilot-scale evaluation the enological traits of a novel, aromatic wine yeast
      strain obtained by adaptive evolution.
AB  - In the competitive context of the wine market, there is a growing interest for
      novel wine yeast strains that have an overall good fermentation capacity and that
      contribute favorably to the organoleptic quality of wine. Using an adaptive
      evolution strategy based on growth on gluconate as sole carbon source, we
      recently obtained wine yeasts with improved characteristics in laboratory-scale
      fermentations. The characteristics included enhanced fermentation rate, decreased
      formation of acetate and greater production of fermentative aroma. We report an
      evaluation of the potential value of the evolved strain ECA5TM for winemaking, by
      comparing its fermentation performance and metabolite production to those of the
      parental strain in pilot-scale fermentation trials, with various grape cultivars
      and winemaking conditions. We show that the evolved strain has outstanding
      attributes relative to the parental wine yeast strain, and in particular the
      production of less volatile acidity and greater production of desirable volatile
      esters, important for the fruity/flowery character of wines. This study
      highlights the potential of evolutionary engineering for the generation of
      strains with a broad range of novel properties, appropriate for rapid application
      in the wine industry.

PMID- 22986199
TI  - Role of selected oxidative yeasts and bacteria in cucumber secondary fermentation
      associated with spoilage of the fermented fruit.
AB  - Changes during the spoilage of fermented cucumber pickles have been attributed to
      the metabolism of different yeasts and bacteria. In this study six organisms
      isolated from commercial spoiled cucumber pickles were evaluated for their
      possible role in primary and secondary cucumber fermentations. The ability of the
      yeasts Issatchenkia occidentalis and Pichia manshurica to utilize lactic and
      acetic acids during aerobic metabolism was confirmed and associated with
      increases in brine pH and the chemical reduction of the fermentation matrix.
      Lactobacillus buchneri and Pediococcus ethanolidurans were able to produce lactic
      acid from sugars, but only L. buchneri produced acetic acid at the expense of
      lactic acid under both aerobic and anaerobic conditions regardless of the initial
      acidic pH of 3.2 in the medium. The formation of secondary products was
      associated with the metabolism of Clostridium bifermentans and Enterobacter
      cloacae, which metabolic activity was observed at medium pH above 4.5.
      Individually, the selected spoilage microorganisms were found to be able to
      produce changes associated with secondary cucumber fermentations. The fact that
      oxidative yeasts and L. buchneri were able to produce chemical changes associated
      with the initiation of the spoilage process indicates that prevention of the
      secondary fermentation could be achieved by inhibiting these organisms.

PMID- 22986200
TI  - Efficacy of the application of a coating composed of chitosan and Origanum
      vulgare L. essential oil to control Rhizopus stolonifer and Aspergillus niger in
      grapes (Vitis labrusca L.).
AB  - This study evaluated the efficacy of the combined application of chitosan (CHI)
      and Origanum vulgare L. essential oil (OV) in the inhibition of Rhizopus
      stolonifer URM 3728 and Aspergillus niger URM 5842 on laboratory media and on
      grapes (Vitis labrusca L.) and its influence on the physical, physicochemical and
      sensory characteristics of the fruits during storage (25  degrees C, 12 days and
      12  degrees C, 24 days). The application of mixtures of different CHI and OV
      concentrations (Minimum Inhibitory Concentration - MIC, 1/2 MIC and 1/4 MIC)
      inhibited the mycelial growth of the test fungi. The application of CHI and OV at
      sub-inhibitory concentrations (CHI 1/2 MIC + OV 1/4 MIC; CHI 1/2 MIC + OV 1/2
      MIC) inhibited spore germination and caused morphological changes in fungal
      spores and mycelia, in addition to inhibiting the growth of the assayed fungi
      strains in artificially infected grapes as well as the autochthonous mycoflora of
      grapes stored at both room and cold temperature. In general, the application of a
      coating composed of CHI and OV at sub-inhibitory concentrations preserved the
      quality of grapes as measured by their physical and physicochemical attributes,
      while some of their sensory attributes improved throughout the assessed storage
      time. These results demonstrate the potential of the combination of CHI and OV at
      sub-inhibitory concentrations to control post-harvest pathogenic fungi in fruits,
      in particular, R. stolonifer and A. niger in grapes.

PMID- 22986201
TI  - Inhibition of Listeria monocytogenes by Enterococcus mundtii isolated from soil.
AB  - Two bacterial isolates with inhibitory activity against Listeria monocytogenes
      and Enterococcus faecalis were obtained from soil. Genotypic and phenotypic
      characterization identified them as Enterococcus mundtii, a species whose ability
      to compete with L. monocytogenes is relatively unexplored compared to other
      members of the genus. The thermal stability of the inhibitory factor and its
      sensitivity to proteolytic enzymes indicate that it is most likely a bacteriocin.
      Both isolates grew at comparable rates to L. monocytogenes at 5  degrees C and 10
      degrees C in vitro. One isolate killed L. monocytogenes when it reached
      concentrations of 10(6)-10(8) CFU ml(-1). Minimum inocula of 10(6) and 10(5) CFU
      ml(-1) of E. mundtii were required to reduce and maintain L. monocytogenes
      concentrations beneath the level of detection at 5  degrees C and 10  degrees C,
      respectively. In situ experiments at 5  degrees C showed that E. mundtii
      inhibited the growth of L. monocytogenes on vacuum-packed cold smoked salmon
      during its four week shelf life. E. mundtii could, therefore, control the growth
      of L. monocytogenes at low temperatures, indicating a potential application in
      controlling this pathogen in chilled foods. To control growth of Listeria, the
      concentration of E. mundtii needs to be high, but it is possible that a purified
      bacteriocin could be used to achieve the same effect.

PMID- 22986202
TI  - Response of Bacillus cereus vegetative cells after exposure to repetitive
      sublethal radiation processing in combination with nisin.
AB  - The present study evaluated the response of Bacillus cereus LSPQ 2872 vegetative
      cells, following exposure to single and repetitive sublethal gamma-radiation
      treatment at 1 kGy alone or in combination with nisin at its maximum tolerated
      concentration, in BHI broth supplemented with 0.5% glucose. Results showed that
      B. cereus has the capability to develop increased resistance to subsequent cycles
      of gamma irradiation and a significant increase (p <= 0.05) of the relative
      radiation resistance (D(10)) value was noticed after the fourth irradiation at 1
      kGy. The sequence and the repetitive sublethal treatment of gamma-radiation with
      nisin affected significantly (p <= 0.05) B. cereus radio-tolerance since lower
      D(10) values were recorded. Our results showed that the response of B. cereus to
      repetitive mild bactericidal treatment was accompanied by relevant modifications
      in the cell properties leading to the increased resistance. Transmission electron
      microscopy revealed that resistance might be related to changes in the cell wall.
      Multiparameter flow cytometry revealed effectively diverse physiological changes
      that B. cereus underwent during development of radio-resistance. The development
      of increased resistance to gamma irradiation was accompanied by an increase of
      the percentage of injured and viable cells at the expense of dead cells. Nisin
      treated cells developed also increased radio-resistance if repetitively processed
      with gamma-radiation at sublethal doses which was not demonstrated by plate
      counting.

PMID- 22986203
TI  - Non-O157 Shiga toxin-producing Escherichia coli in retail ground beef and pork in
      the Washington D.C. area.
AB  - The prevalence and characteristics of non-O157 Shiga toxin-producing Escherichia
      coli (STEC) in retail ground meat from the Washington D.C. area were investigated
      in this study. STEC from 480 ground beef and pork samples were identified using
      PCR screening followed by colony hybridization. The STEC isolates were
      serogrouped and examined for the presence of virulence genes (stx1, stx2, eae and
      hlyA), and antimicrobial susceptibility. PFGE was used to identify the clonal
      relationships of STEC isolates, and PCR-RFLP was employed to determine stx
      subtypes. In addition, the cytotoxicity of STEC isolates was determined using a
      Vero cell assay. STEC were identified in 12 (5.2%) of 231 ground pork and 13
      (5.2%) of 249 ground beef samples. Among 32 STEC isolates recovered from the 25
      samples, 12 (37.5%) carried stx2dact and 7 (21.9%) carried hlyA, but none carried
      eae. Nine isolates were identified as O91, and 17 (53.1%) isolates were resistant
      to two or more antimicrobials. Verotoxicity was detected in 26 (81.3%) of the
      STEC isolates. Thus, the retail ground meat was contaminated with a heterogeneous
      population of non-O157 STEC, some of which were potential human pathogens.

PMID- 22986204
TI  - Modelling Aspergillus flavus growth and aflatoxins production in pistachio nuts.
AB  - Aflatoxins (AFs) are the main contaminants in pistachio nuts. AFs production in
      pistachio has been attributed to Aspergillus flavus. The aim of this study was to
      apply existing models to predict growth and AFs production by an A. flavus
      isolated from pistachios as a function of moisture content and storage
      temperature of pistachios in order to test their usefulness and
      complementarities. A full factorial design was used: the moisture content levels
      assayed were 10, 15, 20, 25 and 30% and incubation temperatures were 10, 15, 20,
      25, 30, 37 and 42  degrees C. Both kinetic and probability models were built to
      predict growth of the strain under the assayed conditions. Among the assayed
      models, cardinal ones gave a good quality fit for radial growth rate data.
      Moreover, the progressive approach, which was developed based on a reduced number
      of experimental points led to an improved prediction in the validation step. This
      is quite significant as may allow for improved experimental designs, less costly
      than full factorial ones. Probability model proved to be concordant in 91% of the
      calibration set observations. Even though the validation set included conditions
      around the growth/no-growth interface, there was a 100% agreement in the
      predictions from the data set (n = 16, cut off = 0.5) after 60 days. Similarly,
      the probability for AF presence was rightly predicted in 89% of the cases.
      According to our results EC maximum aflatoxin levels would be surpassed in a
      period as short as 1 month if pistachio nuts reach 20  degrees C, unless %mc is
      <=10%.

PMID- 22986205
TI  - Screening of different stress factors and development of growth/no growth models
      for Zygosaccharomyces rouxii in modified Sabouraud medium, mimicking intermediate
      moisture foods (IMF).
AB  - The microbial stability of intermediate moisture foods (IMF) is linked with the
      possible growth of osmophilic yeast and xerophilic moulds. As most of these
      products have a long shelf life the assessment of the microbial stability is
      often an important hurdle in product innovation. In this study a screening of
      several Zygosaccharomyces rouxii strains towards individual stress factors was
      performed and growth/no growth models were developed, incorporating a(w), pH,
      acetic acid and ethanol concentrations. These stress factors are important for
      sweet IMF such as chocolate fillings, ganache, marzipan, etc. A comparison was
      made between a logistic regression model with and without the incorporation of
      time as an explanatory variable. Next to the model development, a screening of
      the effect of chemical preservatives (sorbate and benzoate) was performed, in
      combination with relevant stress factors within the experimental design of the
      model. The results of the study showed that the influence of the investigated
      environmental stress factors on the growth/no growth boundary of Z. rouxii is the
      most significant in the first 30-40 days of incubation. Incorporating time as an
      explanatory variable in the model had the advantage that the growth/no growth
      boundary could be predicted at each time between 0 and 60 days of incubation at
      22  degrees C. However, the growth/no growth boundary enlarged significantly
      leading to a less accurate prediction on the growth probability of Z. rouxii. The
      developed models can be a useful tool for product developers of sweet IMF.
      Screening with chemical preservatives revealed that benzoic acid was much less
      active towards Z. rouxii than sorbic acid or a mixture of both acids.

PMID- 22986206
TI  - Quantitative real-time PCR method with internal amplification control to quantify
      cyclopiazonic acid producing molds in foods.
AB  - A quantitative TaqMan real-time PCR (qPCR) method that includes an internal
      amplification control (IAC) to quantify cyclopiazonic acid (CPA)-producing molds
      in foods has been developed. A specific primer pair (dmaTF/dmaTR) and a TaqMan
      probe (dmaTp) were designed on the basis of dmaT gene which encodes the enzyme
      dimethylallyl tryptophan synthase involved in the biosynthesis of CPA. The IAC
      consisted of a 105 bp chimeric DNA fragment containing a region of the hly gene
      of Listeria monocytogenes. Thirty-two mold reference strains representing CPA
      producers and non-producers of different mold species were used in this study.
      All strains were tested for CPA production by high-performance liquid
      chromatography-mass spectrometry (HPLC-MS). The functionality of the designed
      qPCR method was demonstrated by the high linear relationship of the standard
      curves relating to the dmaT gene copy numbers and the Ct values obtained from the
      different CPA producers tested. The ability of the qPCR protocol to quantify CPA
      producing molds was evaluated in different artificially inoculated foods. A good
      linear correlation was obtained over the range 1-4 log cfu/g in the different
      food matrices. The detection limit in all inoculated foods ranged from 1 to 2 log
      cfu/g. This qPCR protocol including an IAC showed good efficiency to quantify CPA
      producing molds in naturally contaminated foods avoiding false negative results.
      This method could be used to monitor the CPA producers in the HACCP programs to
      prevent the risk of CPA formation throughout the food chain.

PMID- 22986207
TI  - Evaluation of fast volatile analysis for detection of Botrytis cinerea infections
      in strawberry.
AB  - Grey mold (Botrytis cinerea) is one of the major phytopathogens causing serious
      losses during strawberry postharvest and storage. B. cinerea-host interaction
      affect emissions of volatile compounds during infection resulting in a
      characteristic earthy, mushroom odor. Therefore, the objective of this study was
      to evaluate two analytical techniques based on fast volatile analysis on their
      performance for monitoring evolution and early detection of B. cinerea infections
      in strawberry. In a first experiment headspace multi-capillary column-ion
      mobility spectrometry (HS MCC-IMS) has been successfully used to evaluate
      development of strawberry aroma during shelflife. In a second experiment the same
      technique has been used to detect the degree of B. cinerea infection through
      changes in the volatile profile. Additionally, these samples were analyzed with
      headspace solid-phase-microextraction fast GC-MS (HS SPME fast GC-MS). Both HS
      MCC-IMS and HS SPME fast GC-MS could determine the changes in volatile
      composition as a function of the degree of B. cinerea infection as determined by
      an enzyme-linked immunosorbent assay (ELISA) and could be used to follow the
      evolution of infection. According to the ELISA data, some fruit were infected
      even without any symptoms and volatiles produced by the fungus may be
      overshadowed by the fruit volatiles. Therefore, both analytical techniques could
      not be used for early detection of B. cinerea infections. After identification of
      the volatile compounds and multivariate data analysis, potential biomarkers
      specific for B. cinerea were highlighted, being 3-methylbutanal, cis-4-decenal, 2
      methyl-1-butanol, 2-methyl-1-propanol, 1-octen-3-one and 1-octen-3-ol.

PMID- 22986208
TI  - Persistence of Salmonella enterica during dehydration and subsequent cold
      storage.
AB  - Despite the fact that Salmonella enterica serotype Typhimurium SL 1344 has served
      as a model pathogen in many studies, information regarding its desiccation
      response is still scarce. In this study, we investigated environmental conditions
      that affect Salmonella survival following dehydration and subsequent cold
      storage, using a 96-well polystyrene plate model. The SL 1344 strain exhibited
      high survival compared with other Typhimurium isolates and S. enterica serotypes.
      Further characterization of desiccation tolerance in this strain revealed that
      temperature, stationary-phase of growth, solid medium, and the presence of
      increasing NaCl concentrations (0.5-5.0%) in the growth medium enhanced
      desiccation tolerance. Dehydration at basic pHs (8-10), or in trehalose, sucrose,
      but not in glycine-betaine, improved bacterial persistence. Dehydrated Salmonella
      survived over 100 weeks at 4  degrees C with a ~5-log reduction in numbers.
      However, viability staining revealed only a ~50% reduction in viable cells,
      suggesting bacterial transition into a viable-but-not-cultivable state (VBNC).
      Addition of chloramphenicol reduced bacterial survival implying that adaptation
      to desiccation stress requires de-novo protein synthesis. Consistent with this
      finding, shortening the dehydration time resulted in lower survival. This study
      emphasizes the impact of environmental conditions on the fate of dried Salmonella
      in the food chain and highlights the potential transition of the pathogen to the
      VBNC state.

PMID- 22986209
TI  - Comparison of different sample preparation procedures for the detection and
      isolation of Escherichia coli O157:H7 and Non-O157 STECs from leafy greens and
      cilantro.
AB  - The FDA Bacteriological Analytical Manual (BAM) method for the
      detection/isolation of Shiga toxin-producing Escherichia coli (STEC) involves
      enrichment of produce rinses, blended homogenates or stomached homogenates.
      However, the effectiveness of rinsing produce to remove attached bacteria is
      largely unknown. Moreover, PCR inhibitors can be released under physical
      treatment. The study objective was to determine the relative effectiveness of
      recovery methods for STEC contaminated produce. Spinach, lettuce, and cilantro
      were contaminated with E. coli O157:H7 or a non-O157 STEC, subjected to both the
      BAM method and a soak method, and tested by real-time PCR and cultural methods.
      For O157:H7 and non-O157:H7 STECs, the soak method was significantly more
      productive than leafy green rinses. Of 320 test portions, PCR of recovered
      colonies confirmed 148 were positive by rinsing and 271 were positive by soaking
      (an 83% increase in sensitivity). For recovery of O157:H7 from cilantro, of 60
      test portions, positives were 38 by soaking, 41 by stomaching, and 28 by
      blending. Soaking and stomaching were significantly more productive than
      blending, although soaking was only arithmetically superior to stomaching. Based
      upon these results, it is recommended that a soak method replace the current BAM
      procedures.

PMID- 22986210
TI  - A combination of two lactic acid bacteria improves the hydrolysis of gliadin
      during wheat dough fermentation.
AB  - The evaluation of gliadin hydrolysis during dough fermentation by using two
      lactic acid bacteria, Lactobacillus plantarum CRL 775 and Pediococcus pentosaceus
      CRL 792, as pooled cell suspension (LAB) or cell free extract (CFE) was
      undertaken. The CFE pool produced a greater (121%) increase in amino acid
      concentration than the LAB pool (70-80%). These results were correlated with the
      decrease (76,100 and 64,300 ppm) in the gliadin concentration of doughs
      supplemented with CFE and LAB, respectively, compared to control doughs. The use
      of LAB peptidases seemed to be a viable technologic alternative to reduce the
      gliadin concentration in wheat dough without using living bacteria as starter.

PMID- 22986211
TI  - Use of near infrared spectroscopy to predict microbial numbers on Atlantic
      salmon.
AB  - The potential of a near infrared spectroscopy (NIR) method to detect as well as
      predict microbial spoilage on Atlantic salmon (Salmo salar) was investigated.
      Principal component analysis (PCA) of the NIR spectra showed clear separation
      between the fresh salmon fillets and those stored for nine days at 4 degrees C
      indicating that NIR could detect spoilage. A partial least squares regression
      (PLS) prediction model for total aerobic plate counts after nine days was
      established using the NIR spectra collected when the fish was fresh to predict
      the number of bacteria that would be present nine days later. The calibration
      equation was good (R(2) = 0.95 and RMSE = 0.12 log cfu/g) although the error of
      the validation curve was larger (R(2) = 0.64 and RMSE = 0.32 log cfu/g). These
      results indicate that with further model development, it may be possible to use
      NIR to predict bacterial numbers, and hence shelf-life, in Atlantic salmon and
      other seafood.

PMID- 22986212
TI  - Total mesophilic counts underestimate in many cases the contamination levels of
      psychrotrophic lactic acid bacteria (LAB) in chilled-stored food products at the
      end of their shelf-life.
AB  - The major objective of this study was to determine the role of psychrotrophic
      lactic acid bacteria (LAB) in spoilage-associated phenomena at the end of the
      shelf-life of 86 various packaged (air, vacuum, modified-atmosphere) chilled
      stored retail food products. The current microbiological standards, which are
      largely based on the total viable mesophilic counts lack discriminatory capacity
      to detect psychrotrophic LAB. A comparison between the total viable counts on
      plates incubated at 30  degrees C (representing the mesophiles) and at 22 
      degrees C (indicating the psychrotrophs) for 86 food samples covering a wide
      range - ready-to-eat vegetable salads, fresh raw meat, cooked meat products and
      composite food - showed that a consistent underestimation of the microbial load
      occurs when the total aerobic mesophilic counts are used as a shelf-life
      parameter. In 38% of the samples, the psychrotrophic counts had significantly
      higher values (+0.5-3 log CFU/g) than the corresponding total aerobic mesophilic
      counts. A total of 154 lactic acid bacteria, which were unable to proliferate at
      30  degrees C were isolated. In addition, a further 43 with a poor recovery at
      this temperature were also isolated. This study highlights the potential fallacy
      of the total aerobic mesophilic count as a reference shelf-life parameter for
      chilled food products as it can often underestimate the contamination levels at
      the end of the shelf-life.

PMID- 22986213
TI  - Presence of some indicator bacteria and diarrheagenic E. coli pathotypes on
      jalapeno and serrano peppers from popular markets in Pachuca City, Mexico.
AB  - The chili pepper is a very important crop in Mexico. Diarrheagenic E. coli
      pathotypes (DEPs) are important foodborne pathogens in different countries
      including Mexico. No data exists on DEPs presence on fresh jalapeno and serrano
      pepper and little data have been published on the microbiological quality of
      these peppers. The frequencies of coliform bacteria (CB), thermotolerant
      coliforms (TC), E. coli and DEPs were determined for jalapeno and serrano
      peppers. Of 100 serrano samples, CB, TC, E. coli and DEPs were identified in 100,
      90, 58 and 36%, respectively. Of 100 jalapeno samples, CB, TC, E. coli and DEPs
      were identified in 100, 88, 38 and 14%, respectively. Identified DEPs included
      enterotoxigenic E. coli (ETEC) and Shiga toxin-producing E. coli (STEC). STEC
      were isolated from 36% of serrano samples and 14% of jalapeno samples. ETEC were
      isolated from 12% of serrano samples and 2% of jalapeno samples. Both STEC and
      ETEC were identified in 14 serrano samples and 2 jalapeno samples. No E. coli
      O157:H7 were detected in any STEC-positive samples. Jalapeno and serrano peppers
      could be an important factor contributing to the endemicity of DEPs-caused
      gastroenteritis in Mexico.

PMID- 22986217
TI  - Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in
      adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs.
AB  - Although a growing body of evidence suggests that soy isoflavones help regulate
      lipid metabolism, the underlying mechanism has not yet been thoroughly clarified.
      The present study was undertaken to determine the effects of soy isoflavones on
      the expression of genes involved in lipid metabolism in different adipose tissue
      depots, skeletal muscle and liver of male Huanjiang mini-pigs, as well as the
      expression of adipokines and myokines. A total of 36 male Huanjiang mini-pigs
      were fed basal diet (control, Con), low-dose soy isoflavones (LSI) and high-dose
      soy isoflavones (HSI). The results showed that LSI and HSI regulated the
      expression of genes involved in the anabolism and catabolism of fatty acids in
      dorsal subcutaneous (DSA), abdominal subcutaneous (ASA) and perirenal (PRA)
      adipose tissue depots, as well as longissimus dorsi muscle (LDM) and liver. LSI
      and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the
      expression of myokines in LDM in male Huanjiang mini-pigs. In addition, soy
      isoflavones regulated plasma glucose, leptin and adiponectin contents after
      treatment for two months. Our results indicate that soy isoflavones, by
      regulating the expression of adipokines and myokines, may regulate the metabolism
      of lipids and could have potential therapeutic applications in lipid
      abnormalities.

PMID- 22986218
TI  - A model for the adoption of ICT by health workers in Africa.
AB  - PURPOSE: To investigate the potential of information and communication technology
      (ICT) adoption among maternal and child health workers in rural Nigeria. METHODS:
      A prospective, quantitative survey design was used to collect data from quasi
      randomly selected clusters of 25 rural health facilities in 5 of the 36 states in
      Nigeria over a 2-month period from June to July 2010. A total of 200 maternal and
      child health workers were included in the survey, and the data were analyzed
      using a modified theory of acceptance model (TAM). RESULTS: There was no
      significant difference between ICT knowledge and attitude scores across states.
      There were significant differences in perceived ease of use (P<.001) and
      perceived usefulness scores (P=.001) across states. Midwives reported higher
      scores on all the constructs but a lower score on endemic barriers (which is a
      more positive outcome). However, the differences were only statistically
      significant for perceived usefulness (P=.05) and endemic barriers (P<.001).
      Regression analysis revealed that there was no interaction between worker group
      and age. Older workers were likely to have lower scores on knowledge and attitude
      but higher scores on perceived ease of use and perceived usefulness. Lastly, we
      found that worker preference for ICT application in health varied across worker
      groups and conflicted with government/employer priorities. CONCLUSIONS: Although
      the objective of this study was exploratory, the results provide insight into the
      intricacies involved in the deployment of ICT in low-resource settings. Use of an
      expanded TAM should be considered as a mandatory part of any pre-implementation
      study of ICT among health workers in sub-Saharan Africa.

PMID- 22986214
TI  - Development of a consensus method for culture of Clostridium difficile from meat
      and its use in a survey of U.S. retail meats.
AB  - Three previously described methods for culture of Clostridium difficile from
      meats were evaluated by microbiologists with experience in C. difficile culture
      and identification. A consensus protocol using BHI broth enrichment followed by
      ethanol shock and plating to selective and non-selective media was selected for
      use, and all participating laboratories received hands-on training in the use of
      this method prior to study initiation. Retail meat products (N = 1755) were
      cultured for C. difficile over 12 months during 2010-2011 at 9 U.S. FoodNet
      sites. No C. difficile was recovered, although other clostridia were isolated.

PMID- 22986219
TI  - The reliability of skeletal age determination in an Iranian sample using Greulich
      and Pyle method.
AB  - BACKGROUND: Since introduction of Greulich and Pyle (GP) method for bone age
      determination, several studies have been performed for evaluation of
      applicability of this method in different geographic and ethnic groups. In this
      study we investigated the accuracy of this method in Iranian population.
      MATERIALS AND METHODS: 425 (303 male and 122 female) healthy children aged
      between 6 and 18 years old, without genetic, metabolic, endocrine, growth or
      nutritional disorders who had plain hand and wrist radiographs were enrolled. All
      radiographs were taken for an indication of trauma from January 2009 to August
      2010. Both sexes were divided into three subgroups (6-10, 10-14, 14-18 years
      old). Skeletal age (SA) was determined according to GP atlas by a radiologist who
      was blind to chronological age (CA). Mean CA was compared with mean SA in whole
      population, each sex group and in each age subgroup. Difference score (DS) was
      calculated by subtracting SA from CA and determined for whole population, each
      sex group and also for each age subgroup. Statistical analysis was performed
      using t-test and ANNOVA correlation test. RESULTS: Considering whole study
      population, mean SA was 12.15+/-4.16 years and mean CA was 12.4+/-4.09 years and
      mean difference score (CA-SA) was 0.25+/-0.95 years. In male subjects mean SA was
      12.68+/-4.07 years and mean CA was 13.04+/-3.93 years and mean difference score
      was 0.37+/-0.98 years (equal to 4.5 months). In female subjects mean SA was
      10.84+/-4.11 and mean CA was 10.81+/-4.06 and mean difference score of girls was 
      0.04+/-0.78 years (equal to -0.5 month). DS shows no significant difference among
      three age subgroups in either male (P(value)=0.63) and female (P(value)=0.59)
      group. CONCLUSION: According to this study skeletal age of boys was 4.5 months
      less than chronological age, but in girls skeletal age was 0.5 month more than
      it. Considering the possibility of few months difference, GP atlas could be
      applicable in Iranian children with acceptable accuracy.

PMID- 22986221
TI  - [Usefulness of group work as a teaching strategy for long-term practical training
      in the 6-year pharmaceutical education].
AB  - At the initiation of long-term practical training in the 6-year pharmaceutical
      education, there are many issues to be solved. For example, it is necessary for
      teaching pharmacists, who are in charge of both staffing and teaching pharmacy
      students, to manage their workload with other staff pharmacists. To overcome this
      situation and to improve the motivation of teaching pharmacists towards student
      practical training, we twice held group work (GW) sessions for teaching
      pharmacists, and then evaluated whether such training was effective for their
      understanding of the Model Core Curriculum for Practical Training and for
      promoting a higher level of motivation. During the two-day GW discussions,
      teaching pharmacists, who work daily in the dispensing area, were separated into
      two groups to discuss teaching skills. A questionnaire survey was completed by
      participants before and after each GW session. According to the survey, more than
      90% of the pharmacists had a higher motivation level for practical training after
      the sessions. Particularly in the second GW training, the response rate of "being
      actively involved" improved from 40% to 70%. Furthermore, "The Educational
      Evaluation Testing" was conducted, which confirmed the increased participant
      comprehension. The median scores of the comprehensive exams significantly
      (p<0.01) improved in twice GW, respectively. Therefore, we conclude that GW
      sessions are a useful tool for both improving professional knowledge about the
      Model Core Curriculum and motivating teaching pharmacists involved in the
      practical training of students. We hope that this exercise will lead to higher
      student motivation and satisfaction during their practical training.

PMID- 22986222
TI  - [Questionnaire survey of air extruded jelly dosage form (I) - oral condition of
      elder patients and applicability of air extruded jelly formulation - ].
AB  - Elderly patients tend to have troubles with oral conditions such as the
      impairment of deglutition capability (difficulty in swallowing), in addition to a
      decline in physical performance. An air extruded jelly formulation (AEJF) has
      been developed as a new formulation consisting of jelly and clean air under
      increased pressure. As jelly is discharged smoothly by pushing the air portion,
      elderly patients are able to easily take jelly from the package. In this study,
      survey questionnaires after a patient's trial of AEJF were conducted to
      characterize the intra-oral condition and reveal the applicability of AEJF in
      elderly patients. The subjects were 108 patients (ranging in age from 50 to 79)
      with chronic diseases who take some oral medicine regularly. A questionnaire on
      the oral state and compliance level was conducted before the trial of AEJF. The
      ratios of subjects with deglutition impairment and dryness of the mouth were
      29.7% and 36.1%, respectively. Non-compliance was observed in 31.5% of the
      subjects. After the trial using AEJF, 94.5% of subjects felt that AEJF was easy
      to swallow. The ratio of the patients expecting AEJF to be an oral formulation
      was 89.3%, and those with an intention of daily use was 83.4%. A majority of the
      subjects, 63.9%, intended to switch their present formulations to AEJF.
      Especially, a high ratio was found among subjects who presently take a powder
      formulation or more than 5 kinds of medicines daily. Based on these results, AEJF
      is expected to improve the adherence of elderly patients to their medicine dosage
      regimens, and to improve compliance among those with oral troubles or some other
      hindrance to compliance.

PMID- 22986220
TI  - Identification of differentially expressed proteins in direct expressed prostatic
      secretions of men with organ-confined versus extracapsular prostate cancer.
AB  - Current protocols for the screening of prostate cancer cannot accurately
      discriminate clinically indolent tumors from more aggressive ones. One reliable
      indicator of outcome has been the determination of organ-confined versus nonorgan
      confined disease but even this determination is often only made following
      prostatectomy. This underscores the need to explore alternate avenues to enhance
      outcome prediction of prostate cancer patients. Fluids that are proximal to the
      prostate, such as expressed prostatic secretions (EPS), are attractive sources of
      potential prostate cancer biomarkers as these fluids likely bathe the tumor.
      Direct-EPS samples from 16 individuals with extracapsular (n = 8) or organ
      confined (n = 8) prostate cancer were used as a discovery cohort, and were
      analyzed in duplicate by a nine-step MudPIT on a LTQ-Orbitrap XL mass
      spectrometer. A total of 624 unique proteins were identified by at least two
      unique peptides with a 0.2% false discovery rate. A semiquantitative spectral
      counting algorithm identified 133 significantly differentially expressed proteins
      in the discovery cohort. Integrative data mining prioritized 14 candidates,
      including two known prostate cancer biomarkers: prostate-specific antigen and
      prostatic acid phosphatase, which were significantly elevated in the direct-EPS
      from the organ-confined cancer group. These and five other candidates (SFN, MME,
      PARK7, TIMP1, and TGM4) were verified by Western blotting in an independent set
      of direct-EPS from patients with biochemically recurrent disease (n = 5) versus
      patients with no evidence of recurrence upon follow-up (n = 10). Lastly, we
      performed proof-of-concept SRM-MS-based relative quantification of the five
      candidates using unpurified heavy isotope-labeled synthetic peptides spiked into
      pools of EPS-urines from men with extracapsular and organ-confined prostate
      tumors. This study represents the first efforts to define the direct-EPS proteome
      from two major subclasses of prostate cancer using shotgun proteomics and
      verification in EPS-urine by SRM-MS.

PMID- 22986223
TI  - Persistent agmination of lymphomatoid papulosis: an ongoing debate.
AB  - BACKGROUND: Persistent agmination of lymphomatoid papulosis (PALP) has been a
      matter of controversy in the literature, some authors suggesting that it
      represents composite lymphoma, others localized lymphomatoid papulosis (LyP).
      PATIENT AND METHODS: A 64-year-old man was referred to our outpatient center
      complaining of papular eruptions lasting 3 years. At physical examination, he
      showed papulonodular lesions on the trunk and extremities. Some patches on the
      trunk and upper arms were also observed. Both types of lesion were biopsied and
      studied on histological, immunohistochemical and molecular grounds. RESULTS: The
      nodular lesion revealed the classical features of LyP type A, while the patch was
      characterized by the presence of a superficial and deep infiltrate with
      perivascular and interstitial location, consisting of mature lymphocytes admixed
      with plasma cells and large atypical cells that became more numerous beneath the
      epidermis. On immunohistochemistry the two lesions presented the same profile.
      CONCLUSION: Our case suggests that PALP does not correspond to localized LyP, as
      it can involve different skin areas since its presentation. Furthermore it rules
      out the possibility that PALP is a composite lymphoma. In fact, the same
      cytological and phenotypic characteristics were detected in all samples,
      including those taken from patchy areas.

PMID- 22986224
TI  - Defining the habenula in human neuroimaging studies.
AB  - Recently there has been renewed interest in the habenula; a pair of small, highly
      evolutionarily conserved epithalamic nuclei adjacent to the medial dorsal (MD)
      nucleus of the thalamus. The habenula has been implicated in a range of
      behaviours including sleep, stress and pain, and studies in non-human primates
      have suggested a potentially important role in reinforcement processing,
      putatively via its effects on monoaminergic neurotransmission. Over the last
      decade, an increasing number of neuroimaging studies have reported functional
      responses in the human habenula using functional magnetic resonance imaging
      (fMRI). However, standard fMRI analysis approaches face several challenges in
      isolating signal from this structure because of its relatively small size, around
      30 mm(3) in volume. In this paper we offer a set of guidelines for locating and
      manually tracing the habenula in humans using high-resolution T1-weighted
      structural images. We also offer recommendations for appropriate pre-processing
      and analysis of high-resolution functional magnetic resonance imaging (fMRI) data
      such that signal from the habenula can be accurately resolved from that in
      surrounding structures.

PMID- 22986225
TI  - Differential renal glomerular changes induced by 5/6 nephrectomization between
      common marmoset monkeys (Callithrix jacchus) and rats.
AB  - We have been investigating the relevance and availability of 5/6 nephrectomized
      (Nx) common marmoset monkeys (Callithrix jacchus) as a chronic renal failure
      model. As a part of this investigation, renal glomerular changes in the Nx
      marmosets were histopathologically and immunohistochemically evaluated, and then
      compared with those in 5/6 Nx SD rats. In the Nx marmosets, the blood and urine
      parameters were elevated, excluding urine protein; histopathologically,
      enlargement of Bowman's capsule and atrophy of the glomeruli were observed in all
      animals, and other slight changes were also observed in 1 or 2 marmosets. There
      were no significant changes in the mesangial matrix injury score, vimentin and
      desmin positivity or the number of WT1 positive cells between the control and Nx
      marmoset groups. On the other hand, in the Nx rats, the blood and urine
      parameters were elevated; histopathologically, various changes were observed in
      the glomeruli, and the mesangial matrix injury score, vimentin and desmin
      positivity were increased, while the number of WT1 positive cells was decreased;
      these histopathological impacts on the renal glomerulus at 13 weeks after Nx in
      rats were more severe than that in the Nx marmosets. Because the glomerular
      basement membrane (GBM) was much thicker in the marmosets than in the rats in
      electron microscopy, the weaker pathological changes in the Nx marmosets might be
      due to the GBM thickness. This study showed for the first time glomerular lesions
      developed in the Nx marmosets, and the possible pathogenesis of the glomerular
      lesions was discussed.

PMID- 22986226
TI  - Development of a new optical device and its feasibility in prostate cancer
      detection.
AB  - AIM: To develop a new optical device (prostate optical device, POD) for
      assessment of prostate tissue stiffness and evaluate its sensitivity and
      specificity in prostate cancer detection. PATIENTS AND METHODS: POD was tested in
      prostate phantoms and in patients with indications for prostate biopsy. Its
      sensitivity and specificity were compared to digital rectal examination (DRE) and
      transrectal ultrasonography (TRUS). RESULTS: POD was able to identify stiffness
      differences on each prostate phantom. 45 patients were included in the study.
      Sensitivity of TRUS (40%) was significantly lower to POD (85.7%) and DRE (74.3%)
      (p = 0.000 and p = 0.003, respectively). There was no statistical difference
      between POD and DRE (p = 0.221). The combination of POD and DRE showed the
      highest sensitivity (88.6%), positive predictive value (81.6%), and negative
      predictive value (42.9%) among all diagnostic tests. CONCLUSIONS: POD identified
      prostatic stiffness differences with the same sensitivity of DRE performed by an
      experienced urologist providing an objective indication for prostate biopsy and
      early prostate cancer detection.

PMID- 22986227
TI  - Hypertransaminasemia in severely malnourished adult anorexia nervosa patients:
      risk factors and evolution under enteral nutrition.
AB  - BACKGROUND & AIMS: Aminotransferase abnormalities have been reported in
      malnourished patients with anorexia nervosa (AN). The aim of this study was to
      identify prevalence and risk factors of hyperaminotransferasemia in an adult
      cohort of AN patients and to describe evolution during nutritional rehabilitation
      with enteral nutrition for a period of 4 weeks. METHODS: Retrospective study of
      all consecutive malnourished (BMI <16) AN adult patients, without previous liver
      diseases or hepatotoxic drugs or alcohol consumption, hospitalized for enteral
      nutrition in a single center between 1998 and 2008. Hypertransaminasemia was
      defined by an increase in AST and (or) ALT >2N. RESULTS: In all, 126 AN patients
      (117 W, 9 M), age 30 +/- 10.8 years, were included. At admission, 54 (43%)
      patients presented hypertransaminasemia. In univariate analysis, risk factors for
      hypertransaminasemia were: lower BMI (11.2 +/- 2 vs. 13 +/- 2, p < 0.0001) and
      age (28 +/- 9 vs. 32 +/- 12, p < 0.05), male sex (p < 0.05) and the pure
      restrictive form (p = 0.07). In multivariate analysis only BMI, at a threshold of
      12, remained significant [OR 3.7, CI: 95% 2.24-5.2]. Normalization of
      aminotransferases at the end of week 4 of enteral nutrition was obtained in 96%.
      Only 2/54 patients (4%) presented a worsening of aminotransferases during the
      refeeding period, including one that died of liver failure. None of the patients
      without hypertransaminasemia admission presented a subsequent elevation. At the
      end of the 4-week refeeding period, the increase in BMI was greater in patients
      without hypertransaminasemia than in those with it (2.0 +/- 0.8 vs. 1.5 +/- 1.0,
      p < 0.0001). CONCLUSION: Elevated transaminases is common in severe malnourished
      AN patients. Four risk factors were identified: young age, low BMI (the only
      independent factor in multivariate analysis), the pure restrictive form of the
      disease and male sex. After 4 weeks of enteral nutrition the evolution is in most
      cases favourable, albeit with a lower increase in BMI, but can be severe. The
      long-term evolution remains to be determined.

PMID- 22986229
TI  - I shouldn't be alive: bone marrow biopsy.

PMID- 22986228
TI  - Breakthrough pulmonary Aspergillus fumigatus infection with multiple triazole
      resistance in a Spanish patient with chronic myeloid leukemia.
AB  - BACKGROUND: An allogeneic hematopoietic cell transplantation (allo-HCT) patient
      presented with chronic pulmonary aspergillosis associated to pulmonary graft
      versus host disease (GVHD) and was treated for a long time with several
      antifungal agents that were administered as prophylaxis, combination therapies,
      and maintenance treatment. The patient suffered from a breakthrough invasive
      pulmonary aspergillosis due to Aspergillus fumigatus after long-term antifungal
      therapy. MATERIAL AND METHODS: Several isolates were analyzed. First isolates
      were susceptible in vitro to all azole agents. However, after prolonged treatment
      with itraconazole and voriconazole a multiple azole resistant A. fumigatus
      isolate was cultured from bronchoalveolar lavage (BAL) when the patient was
      suffering from an invasive infection, and cavitary lesions were observed.
      RESULTS: Analysis of the resistant mechanisms operating in the last strain led us
      to report the first isolation in Spain of an azole resistant A. fumigatus strain
      harboring the L98H mutation in combination with the tandem repeat (TR) alteration
      in CYP51A gene (TR-L98H). Long-term azole therapy may increase the risk of
      resistance selecting strains exhibiting reduced susceptibility to these
      compounds. However, since the isolates were genetically different the suggestion
      that could be made is that the resistance was not induced during the prolonged
      azole therapy but the patient might simply have acquired this resistant isolate
      from the environment, selected by the therapy. CONCLUSIONS: These findings
      suggest that in all long-term treatments with antifungal agents, especially with
      azoles, repeated sampling and regular susceptibility testing of strains isolated
      is necessary as resistant isolates could be selected.

PMID- 22986230
TI  - Photodynamic therapy activated signaling from epidermal growth factor receptor
      and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and
      lung cancer.
AB  - Patients with serosal (pleural or peritoneal) spread of malignancy have few
      definitive treatment options and consequently have a very poor prognosis. We have
      previously shown that photodynamic therapy (PDT) can be an effective treatment
      for these patients, but that the therapeutic index is relatively narrow. Here, we
      test the hypothesis that EGFR and STAT3 activation increase survival following
      PDT, and that inhibiting these pathways leads to increased PDT-mediated direct
      cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that
      BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear
      translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT
      mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT
      mediated activation of EGFR were also observed in response to BPD-mediated PDT in
      multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and
      was observed to occur in response to porfimer sodium-mediated PDT. In addition,
      we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR
      association and that inhibiting STAT3 signaling prior to PDT leads to increased
      PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to
      increased PDT cytotoxicity through a mechanism that involves increased apoptotic
      cell death. Taken together, these results demonstrate that PDT stimulates the
      nuclear accumulation of both EGFR and STAT3 and that targeting these survival
      pathways is a potentially promising strategy that could be adapted for clinical
      trials of PDT for patients with serosal spread of malignancy.

PMID- 22986231
TI  - Isolated central nervous system progression on Crizotinib: an Achilles heel of
      non-small cell lung cancer with EML4-ALK translocation?
AB  - Advanced non-small lung cancer (NSCLC) remains almost uniformly lethal with
      marginal long-term survival despite efforts to target specific oncogenic
      addiction pathways that may drive these tumors with small molecularly targeted
      agents and biologics. The EML4-ALK fusion gene encodes a chimeric tyrosine kinase
      that activates the Ras signaling pathway, and this fusion protein is found in
      approximately 5% of NSCLC. Targeting EML4-ALK with Crizotinib in this subset of
      NSCLC has documented therapeutic efficacy, but the vast majority of patients
      eventually develop recurrent disease that is often refractory to further
      treatments. We present the clinicopathologic features of three patients with
      metastatic NSCLC harboring the EML4-ALK translocation that developed isolated
      central nervous system (CNS) metastases in the presence of good disease control
      elsewhere in the body. These cases suggest a differential response of NSCLC to
      Crizotinib in the brain in comparison to other sites of disease, and are
      consistent with a previous report of poor CNS penetration of Crizotinib. Results
      of ongoing clinical trials will clarify whether the CNS is a major sanctuary site
      for EML4-ALK positive NSCLC being treated with Crizotinib. While understanding
      molecular mechanisms of resistance is critical to overcome therapeutic
      resistance, understanding physiologic mechanisms of resistance through analyzing
      anatomic patterns of failure may be equally crucial to improve long-term survival
      for patients with EML4-ALK translocation positive NSCLC.

PMID- 22986232
TI  - Sorafenib inhibits p38alpha activity in colorectal cancer cells and synergizes
      with the DFG-in inhibitor SB202190 to increase apoptotic response.
AB  - In the search for new strategies to efficiently fight colorectal cancer, efforts
      are being increasingly focused on targeting regulatory signaling pathways
      involved in cancer-specific features. As a result, several studies have recently
      addressed the therapeutic potential of molecularly-targeted drugs capable of
      inhibiting the activity of protein kinases involved in relevant signaling
      cascades. Here we show that simultaneous inhibition of the DFG-in and DFG-out
      conformations of p38alpha by means of type-I and type-II inhibitors is beneficial
      to impair more efficiently its kinase activity. Moreover, we found that SB202190
      (type-I) and sorafenib (type-II) synergize at the molecular and biological level,
      as co-treatment with these compounds enhances tumor growth inhibition and
      induction of apoptosis both in colorectal cancer cell lines and animal models.
      These results support the need to reconsider sorafenib as a therapeutic agent
      against colorectal cancer and provide new insights that underline the importance
      to elucidate the activity of protein kinase inhibitors for the treatment of
      colorectal carcinoma.

PMID- 22986233
TI  - Pulmonary well-differentiated fetal adenocarcinoma with platelet-derived growth
      factor receptor (PDGFR)alpha expression.
AB  - Well-differentiated fetal adenocarcinoma (WDFA) is a rare pulmonary malignancy.
      Biomarkers of tumor biology has rarely been studied in WDFA. Here, we report two
      WDFA patients. Both patients had blood-streaked sputum or mild hemoptysis at
      presentation. They underwent lobectomy and systematic mediastinal
      lymphadenectomy. Expression of PDGFRalpha on the plasma membrane was demonstrated
      by immunohistochemistry (IHC) in the resected tumor specimens. Further IHC
      examination showed intense immunostaining of beta-catenin in both patients but
      negative staining for TP53, CEA, CD56, EGFR, CK5/6, HER2, S-100, ER, PR, BCL2,
      and NSE. Both patients had no recurrence to date after more than 3 years of
      follow up. Herein, we reviewed this rare disease with special emphasis on the
      clinico-pathological features, treatment and potential role of PDGFRalpha.

PMID- 22986234
TI  - Protective effects of alanyl-glutamine supplementation against nelfinavir-induced
      epithelial impairment in IEC-6 cells and in mouse intestinal mucosa.
AB  - PURPOSE: Human Immunodeficiency Virus (HIV) protease inhibitors (PI) remain a
      crucial component of highly active therapy (HAART) and recently have been
      demonstrated to have potent antitumor effect on a wide variety of tumor cell
      lines. However, discontinuation of therapy is an important issue, which may be
      related to various side-effects, especially diarrhea. The aim of this study was
      to evaluate the effects of nelfinavir (NFV), an HIV PI, and of alanyl-glutamine
      (AQ) supplementation, on intestinal cell migration, proliferation, apoptosis and
      necrosis, using IEC-6 cells and on intestinal crypt depth, villus length, villus
      area, mitotic index and apoptosis in Swiss mice. METHODS: Migration was evaluated
      at 12 and 24 h after injury using a wound healing assay. Cellular proliferation
      was measured indirectly at 24 and 48 h using tetrazolium salt WST-1. Apoptosis
      and necrosis were measured by flow cytometry using the Annexin V assay.
      Intestinal morphometry and mitotic index in vivo were assessed following a seven
      day treatment with 100 mg/kg of NFV, given orally. In vivo proliferation and
      apoptosis were evaluated by intestinal crypt mitotic index and
      immunohistochemistry, respectively. RESULTS: In vitro, AQ supplementation
      enhanced IEC-6 cell migration and proliferation, following challenge with NFV. In
      vivo, AQ increased intestinal villus length, villus area, crypt depth and cell
      proliferation and cell migration, following treatment with NFV. AQ did not
      decrease cell death induced by NFV both in vivo and in vitro. CONCLUSIONS: AQ
      supplementation is potentially beneficial in preventing the effects of PIs, such
      as NFV, in the intestinal tract.

PMID- 22986235
TI  - Emotional memory consolidation impairment induced by histamine is mediated by H1
      but not H2 receptors.
AB  - Histaminergic fibers are present in the molecular and granular layers of the
      cerebellum and have high density in the vermis and flocculus. Evidence indicates
      that the cerebellar vermis is involved in memory consolidation. Recently, we
      demonstrated that when histamine is microinjected into the cerebellar vermis it
      results in impaired emotional memory consolidation in mice that are submitted to
      the elevated plus maze (EPM). This study investigated whether histamine
      impairment was mediated by the H(1) or H(2) receptors. The cerebellar vermis of
      male mice (Swiss Albino) were implanted using a guide cannula. Three days after
      recovery, behavioral tests were performed in the EPM on two consecutive days
      (Trial 1 and Trial 2). Immediately after exposure to the EPM (Trial 1), animals
      received a microinjection of histaminergic drugs. In Experiment 1, saline (SAL)
      or histamine (HA, 4.07 nmol/0.1 MUl) was microinjected 5 min after pretreatment
      with the H(1) antagonist chlorpheniramine (CPA, 0.16 nmol/0.1MUl) or SAL. In
      Experiment 2, SAL or HA was microinjected into the mice 5 min after pretreatment
      with the H(2) antagonist ranitidine (RA, 2.85 nmol/0.1 MUl) or SAL. Twenty-four
      hours later, the mice were re-exposed to the EPM (Trial 2) under the same
      experimental conditions but did not receive an injection. On both days, the test
      sessions were recorded to enable analysis of the behavioral measures. The
      decrease in open arm exploration (% entries and % time spent in the open arms) in
      Trial 2 relative to Trial 1 was used as a measure of learning and memory. The
      data were analyzed using the two-way analysis of variance (ANOVA) and Duncan's
      tests. In Experiment 1, the Duncan's test indicated that the mice entered the
      open arms less often (%OAE) and spent less time in the open arms (%OAT) in Trial
      2 after being microinjected with SAL+SAL, SAL+CPA and CPA+HA. However, the
      animals that received SAL+HA did not enter the open arms less frequently or spend
      less time in them, which was significantly different from the CPA+HA group. The
      results of Experiment 2 demonstrated that the %OAE and %OAT in Trial 2 were
      different from Trial 1 for the groups that were microinjected with SAL+SAL and
      SAL+RA. The animals that were microinjected with RA+HA or with SAL+HA did not
      show a reduction in %OAE. These results demonstrate that the animals treated with
      HA did not avoid the open arms less on retesting and indicated that CPA did not
      alter the behavior parameters but did revert the histamine-induced impairment of
      memory consolidation. Furthermore, the H(2) antagonist RA, at the dose used in
      this study, did not affect memory consolidation and failed to revert histamine
      induced impairment.

PMID- 22986236
TI  - Mitochondrial dysfunction in human TDP-43 transfected NSC34 cell lines and the
      protective effect of dimethoxy curcumin.
AB  - TAR-DNA-binding protein of 43kDa (TDP-43) was recently found to be one of the
      major disease proteins in the pathological inclusions of amyotrophic lateral
      sclerosis (ALS). The effect of TDP-43 on mitochondrial function remains poorly
      understood. Here, we show that human TDP-43 caused mitochondrial morphologic
      abnormality, decrease of mitochondrial complex I activity and mitochondrial
      transmembrane potential, and increased expression of mitochondrial uncoupling
      protein 2 (UCP2) in human TDP-43 stably transfected NSC-34 cells by using flow
      cytometric analysis, spectrophotometric assays, electron microscopy and Western
      blotting. We also show that dimethoxy curcumin (DMC) could ameliorate
      mitochondrial dysfunction in mutated TDP-43 stably transfected cell lines. DMC
      could be potentially useful for neurodegenerative diseases linked with mutated
      TDP-43.

PMID- 22986238
TI  - Bilateral gingival enlargement of the posterior mandible in an adolescent child.

PMID- 22986239
TI  - Topical pregabalin and diclofenac for the treatment of neuropathic orofacial pain
      in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of topical treatment
      with pregabalin and diclofenac on neuropathic orofacial pain induced by
      infraorbital nerve injury in the rat. STUDY DESIGN: Sixty-four Sprague-Dawley
      rats underwent infraorbital nerve injury. Seven days after surgery, pain was
      verified and the rats randomly assigned to topical or systemic treatment with
      pregabalin or diclofenac, or to no treatment. Pain intensity and motor
      coordination were assessed at baseline, after surgery, and daily after treatment
      for 4 consecutive days. Medication plasma levels were assessed at the end of the
      study. RESULTS: Topical treatment with 10% pregabalin or 5% diclofenac reduced
      the pain significantly. A significant decrease in motor coordination was found in
      the systemic pregabalin. The medications' plasma levels were significantly higher
      in the systemic treatment compared with the topical. CONCLUSIONS: Topical
      treatment with pregabalin or diclofenac can reduce neuropathic orofacial pain
      induced by nerve injury.

PMID- 22986240
TI  - Kinesiographic recordings of jaw movements are not accurate to detect magnetic
      resonance-diagnosed temporomandibular joint (TMJ) effusion and disk displacement:
      findings from a validation study.
AB  - OBJECTIVE: The aim of this study was to perform a validation study assessing the
      correlation between magnetic resonance (MR) findings of temporomandibular joint
      (TMJ) disk displacement and effusion and some parameters drawn from
      kinesiographic (KG) recordings of jaw motion, i.e., deflection, deviations,
      incisures. STUDY DESIGN: Thirty-one patients with TMJ disorders underwent a
      kinesiographic recording in the same day in which the MR was performed.
      Regression analysis was performed to assess the correlation between the MR and KG
      findings. RESULTS: MR findings were not correlated with KG parameters (P > .05).
      The accuracy of all KG variables for diagnosing MR-detected signs was low. KG
      deflection ranged from 38.7% to 54.8%, KG deviation from 42% to 54.8%, and KG
      incisures from 9.6% to 71%. Specificity and positive predictive values were far
      from acceptable levels for all KG variables. CONCLUSIONS: The findings do not
      support the usefulness of jaw-tracking devices in dental practices that diagnose
      and manage temporomandibular disorders.

PMID- 22986241
TI  - Risk of postoperative bleeding after dental procedures in patients on warfarin: a
      retrospective study.
AB  - OBJECTIVES: The purpose of this retrospective study was to investigate the
      frequency of bleeding complications after invasive dental procedures in
      warfarinized patients and the possible risk factors. STUDY DESIGN: The CoaguChek
      System was used to obtain an in-office international normalized ratio (INR) value
      for 122 patients (240 appointments), of which the mean age was 57.0 +/- 15.9
      years and 50% were males. Demographic and clinical information were obtained
      retrospectively from dental and medical records. RESULTS: Five episodes (mean
      INR: 2.0 +/- 0.8) of persistent bleeding were identified; 4 were after
      extractions and 1 was after implant placement. The frequency of bleeding was
      4.8%, if only considering surgical procedures. Postoperative bleeding was
      significantly higher (P < .05) in patients who were taking anti-thrombotic
      medications in addition to warfarin. CONCLUSIONS: There is a low incidence of
      persistent bleeding after invasive dental procedures in warfarinized patients but
      the risk appears to increase with the use of concomitant anti-thrombotic
      medications.

PMID- 22986242
TI  - Comparison of denture microwave disinfection and conventional antifungal therapy
      in the treatment of denture stomatitis: a randomized clinical study.
AB  - OBJECTIVE: The aim of this study was to compare the effectiveness of denture
      microwave disinfection and antifungal therapy on treatment of denture stomatitis.
      STUDY DESIGN: Sixty denture wearers with denture stomatitis (3 groups; n = 20
      each), were treated with nystatin or denture microwave disinfection (1 or 3
      times/wk) for 14 days. Mycologic samples from palates and dentures were
      quantified and identified with the use of Chromagar, and clinical photographs of
      palates were taken. Microbiologic and clinical data were analyzed with the use of
      a series of statistical tests (alpha = .05). RESULTS: Both treatments similarly
      reduced clinical signs of denture stomatitis and growth on palates and dentures
      at days 14 and 30 (P > .05). At sequential appointments, the predominant species
      (P < .01) isolated was C. albicans (range 98%-53%), followed by C. glabrata
      (range 22%-12%) and C. tropicalis (range 25%-7%). CONCLUSIONS: Microwave
      disinfection, at once per week for 2 treatments, was as effective as topical
      antifungal therapy for treating denture stomatitis.

PMID- 22986243
TI  - Quantification by energy dispersive x-ray spectroscopy of alendronate in the
      diseased jaw bone of patients with bisphosphonate-related jaw osteonecrosis.
AB  - OBJECTIVE: Recently, specific in vitro bisphosphonate concentrations have been
      established for reaching a toxic threshold that could result in the induction of
      bisphosphonate-related osteonecrosis of the jaw (BRONJ), but these data have not
      been validated in vivo. The purpose of this study was to quantify the
      concentration of bisphosphonates (BPs) in the diseased jaw bone of patients
      experiencing BRONJ. STUDY DESIGN: We hypothesized that if the average natural
      nitrogen content of mammalian bone is known, the excess of nitrogen in the jaw
      bone of BRONJ patients is likely to reflect the concentration of amino-BP. To
      test our hypothesis, jaw bone specimens from patients with BRONJ were acquired
      after sequestrectomy and analyzed by energy-dispersive X-ray spectroscopy (EDS).
      RESULTS: The EDS analysis of the bone demonstrated a highly linear correlation
      between increasing concentrations of BP and the increasing percentage of nitrogen
      measured at the bone surfaces (R(2) = .9851, P = .0149). CONCLUSIONS: SEM/EDS can
      be a valuable tool for assessing BP concentration in jaw bone and provides
      important insight into BP pharmacokinetics and BRONJ.

PMID- 22986244
TI  - Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and growth
      factors regulate the aggressiveness and proliferative activity of keratocystic
      odontogenic tumors.
AB  - OBJECTIVE: The objective of this preliminary study was to evaluate the expression
      of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases
      (TIMPs) and growth factors in keratocystic odontogenic tumors (KOTs). STUDY
      DESIGN: The expression of MMPs, TIMPs, growth factors, and the extracellular
      signal-regulated kinase (ERK) 1/2 signaling pathway were assessed by
      immunohistochemistry in 15 cases of KOT and 4 cases of calcifying cystic
      odontogenic tumor (CCOT). RESULTS: KOT samples expressed significantly higher
      amounts of MMPs, TIMPs, growth factors, epidermal growth factor receptor (EGFR),
      and ERK compared with CCOT samples, with the exception of MMP-2 and TIMP-1.
      CONCLUSIONS: MMP-9, TIMP-2, EGF and transforming growth factor alpha act together
      and likely regulate the proliferation and aggressiveness of KOT. ERK-1/2 serves
      as the transducer of signals generated by these proteins, which signal through
      the common receptor, EGFR. This process may be related to the increased
      proliferation and aggressiveness observed in KOT.

PMID- 22986245
TI  - Expression of midkine in ameloblastomas and its correlation with
      clinicopathologic parameters.
AB  - OBJECTIVE: Midkine (MK) is a heparin-binding growth factor that is overexpressed
      in various human cancers. The aim of this study was to investigate the expression
      of MK in ameloblastomas and correlate the results with clinicopathologic
      parameters. STUDY DESIGN: Cases of ameloblastoma seen between 1999 and 2010 were
      identified. Clinical information was collected regarding age, gender, race, and
      location of tumor. Cases were classified as solid/multicystic, unicystic, and
      peripheral. The expression of midkine was assessed using immunohistochemistry. A
      significant difference was considered present at P < 0.05. RESULTS: A total of 34
      cases of ameloblastoma and 4 cases of ameloblastic carcinomas were identified. MK
      was expressed in 67% of lesions (23.5% weak expression; 14.7% moderate
      expression; 29.4% strong expression). A significant difference was seen between
      solid/multicystic and unicystic lesions. CONCLUSIONS: MK is expressed in the
      majority of ameloblastomas, suggesting a role of the protein in the tumor's
      development, progression, and behavior.

PMID- 22986246
TI  - Peritrabecular clefting in fibrous dysplasia of the jaws: an important
      histopathologic feature for differentiating fibrous dysplasia from central
      ossifying fibroma.
AB  - OBJECTIVE: The aim of this multicenter study was to perform a histomorphometric
      analysis of peritrabecular clefting in fibrous dysplasia (FD) in an attempt to
      obtain data that could be useful for distinguishing between FD and ossifying
      fibroma (OF). STUDY DESIGN: A clinicopathologic analysis was performed in 68
      patients diagnosed with FD and 37 patients diagnosed with OF. Histologic sections
      were scanned using an Aperio ScanScope CS. A histomorphometric analysis was
      performed with the aid of an image analyzer (UTHSCSA Image Tool 3.0 version) on
      37 randomly selected samples of FD, and the results were compared with the 37 OF
      specimens. RESULTS: The presence of peritrabecular clefting was observed in 32
      (86.5%) cases of FD, whereas no case of OF presented peritrabecular clefting.
      CONCLUSIONS: Peritrabecular clefting may be a hallmark of the lesions in patients
      with FD, and it may be a valuable microscopic feature for distinguishing it from
      OF.

PMID- 22986247
TI  - The clinical and histologic presentation of gingival squamous cell carcinoma: a
      study of 519 cases.
AB  - OBJECTIVES: Gingival squamous cell carcinoma (SCCA) often presents with benign
      features, which may lead to delay in treatment. This study describes the clinical
      and histologic characteristics of a series of gingival SCCA cases. STUDY DESIGN:
      A retrospective consecutive case review was performed using the University of
      Florida College of Dentistry Biopsy service's database, which yielded clinical
      and histologic information on 519 cases of gingival SCCA. RESULTS: The average
      age of affected patients was 72.3 years. The most common site was the mandibular
      posterior gingiva. Approximately 72% of lesions were present for >2 months at
      biopsy. The majority of clinicians considered a malignancy in their differential
      diagnosis (64%), although 15% considered only reactive lesions. Most of the
      carcinomas presented as exophytic masses and, histologically, were moderately
      differentiated. CONCLUSIONS: Gingival SCCA may present with varied clinical and
      histologic appearances and should be considered in the differential diagnosis of
      benign appearing lesions of the gingiva.

PMID- 22986248
TI  - Preoperative evaluation of patients with squamous cell carcinoma of the oral
      cavity: fluorine-18 fluorodeoxyglucose positron emission tomography/computed
      tomography and ultrasonography versus histopathology.
AB  - BACKGROUND: The purpose of this retrospective study was to compare fluorine-18
      fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and
      ultrasonography (US) in the staging of patients with squamous cell carcinoma of
      the oral cavity. METHODS: We compared preoperative evaluations regarding lymph
      nodes using PET/CT, US, and both methods. The cutoff for the maximum standardized
      uptake value (SUV(max)) in PET/CT was set at 2.7 by a receiver operating
      characteristic analysis that was based on the histopathological diagnosis. US was
      used to examine internal structural changes on B-mode and hilar vascularity on
      power Doppler. RESULTS: The performance of PET/CT and US in combination was
      better than that of each modality separately. However, there were
      histopathological changes that could not be detected on PET/CT or US. PET/CT
      could not detect nodes with necrotic or cystic changes. US could not detect lymph
      nodes that did not have abnormal structures. CONCLUSIONS: PET/CT and US are
      complementary tools to evaluate preoperative patients.

PMID- 22986249
TI  - Do carotid atheromas on panoramic images prognosticate arterial calcifications on
      mammograms: acknowledged markers of future adverse cardiovascular events?
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between
      calcified carotid artery plaque (CCAP) on panoramic images and breast arterial
      calcifications (BAC) on mammograms, a validated independent risk indicator of
      fatal myocardial infarctions and strokes. MATERIALS AND METHODS: Women >=55 years
      old having CCAP diagnosed by their dentists had their mammograms evaluated for
      BAC by a physician. Other study variables were age, ethnicity, body mass index,
      and medications for hypertension, diabetes, and dyslipidemia. Descriptive and
      bivariate statistics and logistic regression were computed. RESULTS: Researchers
      identified 40 women (mean age 62.2 +/- 6.2 years old) with CCAP, of whom 9
      (prevalence rate 22.5%) also had BAC. The women with BAC tended to be older (65.1
      vs 61.3 years old), more frequently hypertensive (100% vs 80.6%), and more
      frequently black than those without BAC, although these differences were not
      statistically significant (P > 0.10). CONCLUSIONS: CCAP on panoramic images of
      women is unrelated to the presence of BAC on mammograms.

PMID- 22986250
TI  - Diagnosis and management of calcified carotid artery atheroma: dental
      perspectives.
AB  - The calcification of cervical carotid artery atheroma (CCAA) represents
      maturation of a lumenal atherosclerotic plaque that has been associated with a
      high risk of cerebral stroke. The demonstration of CCAA on rotational panoramic
      images has received increasing attention in dentistry since it was first
      described in 1981. The purposes of this article are to provide a background to
      the mechanism of arterial calcification, to review the clinical diagnostic and
      management algorithms for dental practitioners when CCAA are identified
      radiologically, and to describe and illustrate current appropriate radiographic
      modalities and medical management strategies used to confirm and assess stenosis
      associated with CCAA.

PMID- 22986252
TI  - Ossifying fibroma of the maxilla: a case report including its imaging features
      and dynamic magnetic resonance imaging findings.
AB  - Ossifying fibroma (OF), a rare nonodontogenic tumor, is defined as a bone-related
      jawbone lesion. The main histopathological feature of OF is the replacement of
      bone by benign connective tissue. Ossifying fibroma usually occurs in the second
      to fourth decades of life and shows a predilection for females. Ossifying fibroma
      most commonly occurs in the mandible, and OF arising from the anterior part of
      the maxilla is rare. Ossifying fibromas display various radiographic findings,
      including varying degrees of radiolucency and radiopacity, depending on the
      proportions of their soft and hard tissue components. Depending on their
      components, it can be difficult to distinguish OF from other fibroosseous lesions
      and some odontogenic tumors by using conventional radiographs, computed
      tomography, and magnetic resonance imaging (MRI). We report a case of OF in the
      anterior maxilla in a 56-year-old man, together with its histopathological and
      imaging findings including the dynamic MRI findings.

PMID- 22986251
TI  - Acute osteomyelitis of the mandible caused by Rhodococcus equi in an
      immunocompromised patient: a case report and literature review.
AB  - We present the first case of acute osteomyelitis of the mandible caused by
      Rhodococcus equi in an immunocompromised patient. A 53-year-old Caucasian man was
      referred to the outpatient clinic, because of a swelling of the left submental
      and submandibular spaces. The patient was immunocompromised owing to medication
      against myasthenia gravis and type II diabetes mellitus. The patient underwent
      surgical debridement under local anesthesia. Histologic examination showed acute
      osteomyelitis and both blood and pus cultures isolated Rhodococcus equi. The
      patient was discharged on linezolid 600 mg orally twice a day for 6 months and
      remains free of the disease 2 years postoperatively. Most patients with
      Rhodococcus infection are immunocompromised. Infection with this organism is rare
      and usually causes a distinct clinical syndrome resembling pulmonary
      tuberculosis. Diagnosis is frequently missed or delayed. Not only clinicians but
      also laboratory specialists should be aware of this organism, so as to contribute
      to prompt diagnosis and treatment of such infections.

PMID- 22986253
TI  - Large arteriovenous malformation of the oromaxillofacial region with multiple
      phleboliths.
AB  - Vascular tumors are the most common benign tumors of the head and neck in infancy
      and childhood. Vascular anomalies of the head and neck were divided into 2
      categories including hemangiomas and vascular malformations. Oral and
      maxillofacial hemangiomas and vascular malformations are congenital lesions with
      various clinical characteristics, manifestations, indications, and possibilities
      for treatment. This paper reports a case of large arteriovenous malformations
      including a description of the features demonstrated by panoramic radiography,
      cone beam computed tomography, and magnetic resonance imaging. The differential
      diagnosis and treatment modalities (including embolization with N
      butylcyanoacrylate in this case) are also discussed following the case
      presentation, along with the available literature review.

PMID- 22986254
TI  - Bizarre parosteal osteochondromatous proliferation of the maxilla: a case report.
AB  - Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion
      of bone, known as Nora's lesion. The lesion often behaves like a malignant tumor,
      clinically and microscopically. BPOP usually occurs in the small tubular bones of
      the hands and feet, and a lesion arising in the oral and maxillofacial region is
      extremely rare. In this report, we present a case of BPOP arising in the maxilla
      of an adult woman, in the absence of trauma. After the initial lesion was
      excised, the patient began orthodontic treatment. The lesion recurred twice, both
      times appearing in almost the same location. Finally, the lesion was excised via
      marginal resection of the maxilla. In this case, it is suspected that the
      orthodontic treatment may have affected the recurrence of BPOP, because there was
      no history of trauma.

PMID- 22986255
TI  - Metachronous clear cell carcinoma of the tongue and kidney: a diagnostically
      challenging coincidence.
AB  - Clear cell carcinomas (CCCs) account for 1% of carcinomas of the salivary glands.
      A 63-year-old woman presented with a painless, nonulcerated, nodular mass on the
      right side of the tongue, without palpable neck nodes. After excision and
      cryotherapy of the mass, the histologic evaluation revealed CCC. At the age of
      55, she had undergone radical nephrectomy for CCC of the kidney which extended
      into the renal vein (pT3aN0). Although she had remained metastasis-free during
      the follow-up, the clear cell morphology raised the possibility of late lingual
      metastasis of the renal CCC. A clinical search for metastases, and a series of
      immunostainings and analysis of the von Hippel-Lindau gene were therefore
      performed on paraffin-embedded blocks of both tumors: Primary metachronous CCC of
      the tongue was diagnosed. This case illustrates the diagnostic challenge posed by
      CCC of the tongue if there is a history of CCC of the kidney.

PMID- 22986256
TI  - Open bite as a complication of total temporomandibular joint replacement: a case
      report.
AB  - Temporomandibular joint total joint replacement, like any surgery, can be
      associated with either intraoperative or postoperative complications.
      Intraoperative complications may include injuries to local anatomical structures
      (e.g., blood vessels, nerves, middle ear, and external auditory canal), or poor
      positioning and/or adaptation of the prosthesis components to the host bone.
      Postoperative complications may include infection, hematoma, heterotopic bone
      formation, implant failure, pain, salivary fistula, foreign body or allergic
      reactions, and malocclusion. This article reports the occurrence of a
      postoperative open-bite malocclusion complication, the result of maxillary artery
      hemorrhage.

PMID- 22986257
TI  - Steroid hormones and the development of reproductive organs.
AB  - It has been more than 150 years since the physiological function of androgen was
      reported for the first time in fowl. This finding has served as a basis for many
      studies focusing on steroid hormones from various aspects. These studies have
      significantly enhanced our knowledge about the structures of steroid hormones,
      their synthetic pathways, enzymes involved in the synthetic pathways, steroid
      hormone-specific receptors, actions of steroid hormones through receptor binding,
      and the differentiation of steroidogenic cells. However, there are still many
      attractive and important issues in these areas, some of which are currently being
      addressed. In this review, we trace the history and findings of the previous
      studies on steroid hormones, summarize our present understanding in this area,
      and discuss issues that remain to be elucidated.

PMID- 22986265
TI  - Analysing and interpreting DNA methylation data.
AB  - DNA methylation is an epigenetic mark that has suspected regulatory roles in a
      broad range of biological processes and diseases. The technology is now available
      for studying DNA methylation genome-wide, at a high resolution and in a large
      number of samples. This Review discusses relevant concepts, computational methods
      and software tools for analysing and interpreting DNA methylation data. It
      focuses not only on the bioinformatic challenges of large epigenome-mapping
      projects and epigenome-wide association studies but also highlights software
      tools that make genome-wide DNA methylation mapping more accessible for
      laboratories with limited bioinformatics experience.

PMID- 22986267
TI  - Microdialysis of ethanol during operant ethanol self-administration and ethanol
      determination by gas chromatography.
AB  - Operant self-administration methods are commonly used to study the behavioral and
      pharmacological effects of many drugs of abuse, including ethanol. However,
      ethanol is typically self-administered orally, rather than intravenously like
      many other drugs of abuse. The pharmacokinetics of orally administered drugs are
      more complex than intravenously administered drugs. Because understanding the
      relationship between the pharmacological and behavioral effects of ethanol
      requires knowledge of the time course of ethanol reaching the brain during and
      after drinking, we use in vivo microdialysis and gas chromatography with flame
      ionization detection to monitor brain dialysate ethanol concentrations over time.
      Combined microdialysis-behavioral experiments involve the use of several
      techniques. In this article, stereotaxic surgery, behavioral training and
      microdialysis, which can be adapted to test a multitude of self-administration
      and neurochemical centered hypotheses, are included only to illustrate how they
      relate to the subsequent phases of sample collection and dialysate ethanol
      analysis. Dialysate ethanol concentration analysis via gas chromatography with
      flame-ionization detection, which is specific to ethanol studies, is described in
      detail. Data produced by these methods reveal the pattern of ethanol reaching the
      brain during the self-administration procedure, and when paired with
      neurochemical analysis of the same dialysate samples, allows conclusions to be
      made regarding the pharmacological and behavioral effects of ethanol.

PMID- 22986266
TI  - Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans.
AB  - Recent years have witnessed a sea change in our understanding of transcription
      regulation: whereas traditional models focused solely on the events that brought
      RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging
      evidence points to the pausing of Pol II during early elongation as a widespread
      regulatory mechanism in higher eukaryotes. Current data indicate that pausing is
      particularly enriched at genes in signal-responsive pathways. Here the evidence
      for pausing of Pol II from recent high-throughput studies will be discussed, as
      well as the potential interconnected functions of promoter-proximally paused Pol
      II.

PMID- 22986270
TI  - Monocyte chemoattractant protein-1 in dogs affected with neoplasia or
      inflammation.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C family
      chemokines, which mobilizes monocytes from bone marrow to the site of
      inflammation. To evaluate the clinical utility of canine MCP-1 as a blood test
      item, we measured serum MCP-1 concentrations in normal and ill dogs. Reference
      interval of canine MCP-1 was established as 115.6-176.9 pg/ml. Serum MCP-1
      concentrations increased in the dogs affected with neoplastic (518.0 +/- 84.8
      pg/ml), inflammatory (257.0 +/- 42.5 pg/ml) or other diseases (360.3 +/- 45.2
      pg/ml). The results showed high sensitivity of MCP-1 to detect neoplasia and
      inflammation. Moreover, MCP-1 increased in some cases in which C-reactive protein
      didn't increase. MCP-1 might be helpful as a screening blood test marker for
      detection of neoplasia and inflammation in dogs.

PMID- 22986269
TI  - Staphylococcus aureus persisters tolerant to bactericidal antibiotics.
AB  - Bacterial persister cells are non- or slow-growing reversible phenotypic variants
      of the wild type, tolerant to bactericidal antibiotics. We analyzed here
      Staphylococcus aureus persister levels by monitoring colony-forming unit counts
      of planktonically grown cells treated with six different antimicrobials over
      time. The model laboratory strains HG001-HG003, SA113 and the small colony
      variant (SCV) strains hemB and menD were challenged by the compounds at different
      logs of minimal inhibitory concentration (MIC) in exponential or stationary
      growth phase. Antibiotic tolerance was usually elevated in SCV strains compared
      to normally growing cells and in stationary versus exponential phase cultures.
      Biphasic killing kinetics, typical for persister cell enrichment, were observed
      in both growth phases under different selective conditions. Treatment of
      exponential phase cultures of HG001-HG003 with 10-fold MIC of tobramycin resulted
      in the isolation of persisters which upon cultivation on plates formed either
      normal or phenotypically stable small colonies. Trajectories of different killing
      curves indicated physiological heterogeneity within persister subpopulations.
      Daptomycin added at 100-fold MIC to stationary phase SA113 cells rapidly isolated
      very robust persisters. Fractions of antibiotic-tolerant cells were observed with
      all S. aureus strains and mutants tested. Our results refute the hypothesis that
      S. aureus stationary phase cells are equivalent to persisters, as not all of
      these cells showed antibiotic tolerance. Isolation of S. aureus persisters of
      different robustness seems to depend on the kind and concentration of the
      antibiotic, as well as on the strain used.

PMID- 22986271
TI  - Intestinal T-cell lymphoma in a fossa (Cryptoprocta ferox).
AB  - A 10-year-old male fossa (Crytoprocta ferox) exhibited clinical signs of
      diarrhea, anorexia and weight loss. Chemistry values and echographic results were
      suggestive of intestinal lymphoma. Postmortem examination revealed severe
      multifocal wall thickening of the small intestine with severe enlargement of the
      pancreatic lymph node. Microscopically, the small intestine was multifocally
      transmurally infiltrated by large neoplastic round cells also found in the
      pancreatic lymph node and the liver. On immunohistochemistry, the neoplastic
      cells stained intensely with CD3 and didn't stain with CD79a. Based on these
      findings, a diagnosis of intestinal T-cell lymphoma with pancreatic lymph node
      and liver involvement was made. To the authors' knowledge, this is the first
      report of a lymphoma with immunohistochemical phenotyping in a fossa.

PMID- 22986272
TI  - Initial detection of a circular genome deletion in a naturally bovine
      papillomavirus-infected sample.
AB  - Bovine papillomavirus type 12 (BPV-12) was recently identified in epithelial
      papillomas on the cattle tongue in our previous study. Along with the full-length
      genome, one deleted circular genome, named BPV-12-del, was detected in the same
      papilloma lesion. BPV-12-del is 3363 base pairs in length, and a total of 3,384
      base pairs, including E1, E2 and E4 genes and partial E7 and L2 ORFs, were
      deleted compared with the complete genome. Real-time PCR results showed that the
      percentage of BPV-12-del was 42% of the total genomes in the sample. Southern
      Blot analysis also confirmed the presence of the deleted genome. This is the
      first report describing a circular genome deletion detected in a naturally BPV
      infected sample.

PMID- 22986273
TI  - Lymphangiomatosis of the systemic skin in an old dog.
AB  - A 13-year-old, neutered male miniature dachshund was presented with a one-month
      history of bilateral symmetrical swelling in the pinnae and carpal, cubital and
      tarsal joints, and swelling in the tail. The lesions were histopathologically
      characterized by multiple dilated lymphatic vessels lined by a single attenuated
      layer of endothelial cells. The subcutis was predominantly involved. A number of
      spindle-shaped cells lining the irregular vessels were observed. Morphological
      atypia was not evident in these cells. Immunohistochemical analyses revealed that
      the proliferating endothelial cells were positive for factor VIII-related antigen
      and CD31. Based on the clinical presentation and histopathological features, the
      dog was diagnosed with lymphangiomatosis. Treatment with anti-inflammatory
      prednisolone improved the symptoms.

PMID- 22986274
TI  - Association between the intrarenal renin-angiotensin system and renal injury in
      chronic kidney disease of dogs and cats.
AB  - The association of renin and angiotensin II, which are potent components of the
      renin-angiotensin system, with the severity of chronic renal disease was
      investigated immunohistochemically in dogs and cats. Immunoreactivities of renin
      and angiotensin II were evaluated quantitatively, and their correlations with the
      degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell
      infiltration and interstitial fibrosis were statistically analyzed.
      Immunoreactivities for renin were detected in afferent arteries in both dogs and
      cats. The score of renin-positive signals showed no correlation with plasma
      creatinine concentration or any of the histopathological parameters, except for
      the diameter of glomeruli in dogs. Immunoreactivities for angiotensin II were
      detected in tubules (primarily proximal tubules) and interstitial mononuclear
      cells in both dogs and cats. The score of tubular angiotensin II correlated with
      glomerulosclerosis and cell infiltration in cats but not in dogs. The score of
      interstitial angiotensin II correlated with plasma creatinine concentration,
      glomerulosclerosis, cell infiltration and fibrosis in dogs and with
      glomerulosclerosis and cell infiltration in cats. In conclusion, the results of
      the study suggest that intrarenal renin-angiotensin system is correlated with the
      severity of kidney disease, with the underlying mechanism differing between dogs
      and cats.

PMID- 22986275
TI  - Effects of tepoxalin and medetomidine on glomerular filtration rate in dogs.
AB  - The objective of this study was to evaluate glomerular filtration rate (GFR) and
      the cardiovascular effects of the combination of tepoxalin (TPX) and medetomidine
      (MED) in dogs. Six healthy dogs of either sex (5 males and 1 female), aged 2.5 +/
      2.2 years and weighing 14.7 +/- 4.4 kg, were studied. Each dog received four
      randomized treatments with a minimum of 1 week between treatments: no medication
      as the control group (C); MED (750 MUg/m(2), intravenously [IV]); TPX (10 mg/kg
      orally for 3 days); and MT (TPX 10 mg/kg orally for 3 days plus MED 750 MUg/m(2),
      IV). Iohexol (300 mg iodine/kg, IV) was injected in all dogs in each treatment as
      an indicator of GFR. Blood samples for serum iohexol clearance analysis were
      collected before and 1, 2, 5, 10, 15, 20, 60, 120, 240 and 360 min after the
      iohexol administration. Rectal temperature, heart rate, respiratory rate and
      direct arterial pressure (AP) were obtained before and 5, 10, 15, 20, 60, 120,
      240 and 360 min after the iohexol injection. GFR did not differ between
      treatments. Heart rate was significantly lower in the MED and MT groups than in C
      or TPX. Mean AP was significantly higher with MT than TPX, but only at 5 min
      after the iohexol injection. TPX, MED and the combination of these two drugs do
      not alter GFR. The combination has minimal effect on cardiovascular variables at
      these doses in healthy dogs.

PMID- 22986276
TI  - Confirmatory factor analysis of the brief version of the recovery assessment
      scale.
AB  - The Recovery Assessment Scale (RAS) is a 41-item scale that assesses perceptions
      of recovery (article by Corrigan, Salzer, Ralph, Sangster, and Keck [Schizophr
      Bull 30:1035-1041, 2004]). This article presents a confirmatory factor structure
      of a brief 20-item version of the RAS and investigates its relation to measures
      of quality of life, symptoms severity, social support, loneliness, and
      functioning. The validation sample included 152 persons with serious mental
      illness living in the community. The results of the confirmatory factor analyses
      of the RAS yielded four factors: personal confidence and hope, willingness to ask
      for help, reliance on others, and no domination by symptoms. Subsequent
      regression analysis showed that these factors were related to some of the
      measures assessed in the study, providing support for the convergent and
      discriminate validity of the RAS. The study findings support the convergent and
      discriminate validity of the brief version of the scale.

PMID- 22986277
TI  - The effect of emotional freedom techniques on stress biochemistry: a randomized
      controlled trial.
AB  - This study examined the changes in cortisol levels and psychological distress
      symptoms of 83 nonclinical subjects receiving a single hour long intervention.
      Subjects were randomly assigned to either an emotional freedom technique (EFT)
      group, a psychotherapy group receiving a supportive interviews (SI), or a no
      treatment (NT) group. Salivary cortisol assays were performed immediately before
      and 30 minutes after the intervention. Psychological distress symptoms were
      assessed using the symptom assessment-45. The EFT group showed statistically
      significant improvements in anxiety (-58.34%, p < 0.05), depression (-49.33%, p <
      0.002), the overall severity of symptoms (-50.5%, p < 0.001), and symptom breadth
      (-41.93%, p < 0.001). The EFT group experienced a significant decrease in
      cortisol level (-24.39%; SE, 2.62) compared with the decrease observed in the SI
      (-14.25%; SE, 2.61) and NT (-14.44%; SE, 2.67) groups (p < 0.03). The decrease in
      cortisol levels in the EFT group mirrored the observed improvement in
      psychological distress.

PMID- 22986278
TI  - Coping skills, mental disorders, and suicide among rural youths in China.
AB  - The strain theory of suicide postulates that psychological strains usually
      precede mental disorders including suicidal behavior. Lack of coping skills is
      one of the four strains. This article focuses on the effect of lack of coping
      skills on individual mental disorders and suicide. Data including 392 suicide
      cases and 416 community-living controls were from a large psychological autopsy
      study conducted in rural China. The Hamilton Depression Rating Scale and the
      Structured Clinical Interview for DSM-III-R were used for the diagnosis of mental
      disorders. Coping skills were measured by the Coping Response Inventory. The
      logical analysis and cognitive avoidance coping skills were negatively associated
      with mental disorders, whereas the taking problem-solving action and
      acceptance/resignation coping skills were positively associated with mental
      disorders. This study supports the hypothesis that lack of coping skills to
      certain strains is likely to lead to mental disorders and suicidal behavior.
      Improving people's coping strategies may be an effective way to lower the
      prevalence of mental disorders and suicide.

PMID- 22986279
TI  - Religiosity, magical ideation, and paranormal beliefs in anxiety disorders and
      obsessive-compulsive disorder: a cross-sectional study.
AB  - The relation between religiosity/spirituality (R/S), personal beliefs, and mental
      health has been extensively studied. However, concerning anxiety disorders (ADs),
      empirical evidence is scarce. This study investigated the differences in R/S and
      magical/paranormal ideation among obsessive-compulsive disorder patients (OCD; n
      = 49), patients with other ADs (n = 36), and healthy controls (HCs; n = 35). Our
      results suggest negative religious coping as being the only parameter showing
      significantly higher scores in OCD and AD participants in comparison with HCs.
      Negative religious coping reflects negative functional expressions of R/S in
      stressful situations. Logistic regression also suggested negative religious
      coping as the strongest predictor of group affiliation to the nonhealthy group.
      Further results show no significant differences between other R/S, magical, and
      paranormal ideation traits among groups. This study underlines an important role
      of negative religious coping in ADs yet does not clearly indicate a specific
      causality. Religious-sensitive treatment targeting cognitive aspects of negative
      religious coping are discussed.

PMID- 22986280
TI  - Religious involvement and DSM-IV 12-month and lifetime major depressive disorder
      among African Americans.
AB  - This study explores relationships between lifetime and 12-month DSM-IV major
      depressive disorder and religious involvement within a nationally representative
      sample of African American adults (n = 3,570). MDD was assessed using the DSM-IV
      World Mental Health Composite International Diagnostic Interview. Multivariate
      findings indicate that reading religious materials were positively associated
      with 12-month (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.001-1.29)
      and lifetime (OR, 1.12; 95% CI, 1.03-1.21) MDD, religious service attendance was
      inversely associated with 12-month and lifetime MDD, and religious coping was
      inversely associated with 12-month MDD (OR, 0.75, 95% CI, 0.57-0.99). Findings
      are discussed in relation to the role of religion for African American mental
      health, prior research on the effects of religious involvement on physical and
      mental health, and theoretical and conceptual models of religion-health
      connections that specify multiple and often divergent pathways (e.g., prevention
      and resource mobilization) by which diverse forms of religious involvement impact
      mental health.

PMID- 22986282
TI  - Presurgical navigated transcranial magnetic brain stimulation for recurrent
      gliomas in motor eloquent areas.
AB  - OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) has been repeatedly
      shown to be comparably accurate to direct cortical stimulation (DCS) for rolandic
      region mapping. However, there are no data on its use for recurrent gliomas in
      which scarring and radiotherapy can impair nTMS. We therefore evaluated the
      accuracy of nTMS versus DCS and functional MRI (fMRI) in recurrent gliomas
      compared to initially operated tumors. METHODS: We examined 8 patients with
      recurrent gliomas and 23 patients with initially operated lesions in or adjacent
      to the precentral gyrus by preoperative nTMS. RESULTS: Preoperative motor mapping
      correlated well with intraoperative DCS in recurrent gliomas (6.2+/-6.0mm), as
      well as in newly diagnosed tumor patients (5.7+/-4.6mm) with no significant
      difference. Compared to fMRI, the difference was larger for upper (recurrent:
      8.5+/-7.2mm; new: 9.8+/-8.6mm) and lower (recurrent: 17.1+/-10.6mm; new: 13.8+/
      13.0mm) extremities, with no significant differences. CONCLUSIONS: When comparing
      nTMS with DCS and fMRI, nTMS is as accurate in recurrent gliomas as it is prior
      to the first operation. It should be considered a helpful modality in recurrent
      glioma patients as well. SIGNIFICANCE: nTMS is also applicable in recurrent
      tumors.

PMID- 22986283
TI  - Neuronal oscillations in the EEG under varying cognitive load: a comparative
      study between slow waves and faster oscillations.
AB  - OBJECTIVE: This study has been specifically designed to investigate very low
      frequency neuronal oscillations (VLFO, <0.5 Hz) during resting states and during
      goal-directed tasks of graded difficulty levels, quantify the changes that the
      slow waves undergo in these conditions and compare them with those for higher
      frequency bands (namely delta, theta and alpha). METHODS: To this end we
      developed a multistage signal processing methodology comprising blind source
      separation coupled with a neural network based feature extraction and
      classification method. RESULTS: Changes in the amplitude and phase of brain
      sources estimates in the VLF band between rest and task were enhanced with
      increased task difficulty, but remained lower than those experienced in higher
      frequency bands. The slow wave variations were also significantly correlated with
      task performance measures, and hence with the level of task-directed attention.
      CONCLUSIONS: These findings suggest that besides their prominent sensitivity to
      external stimulation, VLFOs also contribute to the cortical ongoing background
      activity which may not be specifically related to task-specific attention and
      performance. SIGNIFICANCE: Our work provides important insight into the
      association between VLF brain activity and conventional EEG frequency bands, and
      presents a novel framework for assessing neural activity during various mental
      conditions and psychiatric states.

PMID- 22986281
TI  - Memory maintenance by PKMzeta--an evolutionary perspective.
AB  - Long-term memory is believed to be maintained by persistent modifications of
      synaptic transmission within the neural circuits that mediate behavior. Thus,
      long-term potentiation (LTP) is widely studied as a potential physiological basis
      for the persistent enhancement of synaptic strength that might sustain memory.
      Whereas the molecular mechanisms that initially induce LTP have been extensively
      characterized, the mechanisms that persistently maintain the potentiation have
      not. Recently, however, a candidate molecular mechanism linking the maintenance
      of LTP and the storage of long-term memory has been identified. The persistent
      activity of the autonomously active, atypical protein kinase C (aPKC) isoform,
      PKMzeta, is both necessary and sufficient for maintaining LTP. Furthermore,
      blocking PKMzeta activity by pharmacological or dominant negative inhibitors
      disrupts previously stored long-term memories in a variety of neural circuits,
      including spatial and trace memories in the hippocampus, aversive memories in the
      basolateral amygdala, appetitive memories in the nucleus accumbens, habit memory
      in the dorsal lateral striatum, and elementary associations, extinction, and
      skilled sensorimotor memories in the neocortex. During LTP and memory formation,
      PKMzeta is synthesized de novo as a constitutively active kinase. This molecular
      mechanism for memory storage is evolutionarily conserved. PKMzeta formation
      through new protein synthesis likely originated in early vertebrates ~500 million
      years ago during the Cambrian period. Other mechanisms for forming persistently
      active PKM from aPKC are found in invertebrates, and inhibiting this atypical PKM
      disrupts long-term memory in the invertebrate model systems Drosophila
      melanogaster and Aplysia californica. Conversely, overexpressing PKMzeta enhances
      memory in flies and rodents. PKMzeta persistently enhances synaptic strength by
      maintaining increased numbers of AMPA receptors at postsynaptic sites, a
      mechanism that might have evolved from the general function of aPKC in
      trafficking membrane proteins to the apical compartment of polarized cells. This
      mechanism of memory may have had adaptive advantages because it is both stable
      and reversible, as demonstrated by the downregulation of experience-dependent,
      long-term increases in PKMzeta after extinction and reconsolidation blockade that
      attenuate learned behavior. Thus, PKMzeta, the "working end" of LTP, is a
      component of an evolutionarily conserved molecular mechanism for the persistent,
      yet flexible storage of long-term memory.

PMID- 22986284
TI  - Comparative incidence rates of mild adverse effects to transcranial magnetic
      stimulation.
AB  - OBJECTIVES: Past research has largely neglected to investigate mild adverse
      effects (MAEs) to transcranial magnetic stimulation (TMS), including headache and
      nausea. Here we explored the relationship between MAEs, participant
      characteristics (age and gender) and protocol parameters, including mode of
      application, coil geometry, stimulated brain region, TMS frequency, TMS
      intensity, and active vs. sham stimulation. METHODS: Data from 1270 standard post
      monitoring forms was obtained from 113 healthy participants. Analyses aimed to
      identify the risk factors associated with MAE reports and specific symptoms.
      RESULTS: The overall rate of MAEs across TMS sessions was ~5%, with ~78% of
      symptoms occurring post-session. Initial TMS sessions were followed by a higher
      MAE incidence rate relative to later testing sessions. No associations between
      participant characteristics, TMS frequency, or intensity were observed.
      CONCLUSIONS: TMS-related MAEs are relatively common and may be exacerbated by
      initial expectations or anxieties of participants. A significant proportion of
      MAEs may reflect reporting of coincidental phenomena that are unrelated to TMS.
      Recommendations for future safety studies are proposed and monitoring
      documentation is provided. SIGNIFICANCE: Our findings illustrate the importance
      of standardized monitoring of MAEs. Such research aids our understanding of how
      MAEs arise and may lead to interventions for reducing their incidence.

PMID- 22986285
TI  - NOD2 signaling and role in pathogenic mycobacterium recognition, infection and
      immunity.
AB  - The Mycobacterium pathogens acquire additional properties to expand their
      pathogenicity and existence spaces. The interaction between pathogenic
      Mycobacterium components and receptors of host innate immune system is critical
      for the infection outcome, particularly for the macrophage activation. NOD2
      (Nucleotide binding oligomerization domain 2), an intracellular pathogen
      recognition sensor, attenuates two key putative host bacterial killing
      mechanisms: interfering the production of TNF-alpha and inducing resistance to
      apoptosis. Multiple evidences have shown that NOD2 acts as a non-redundant
      recognition system of Mycobacterium, a successful pathogen with many mechanisms
      to evade host immunity and leading to insidious disease. Understanding the
      complex interaction between host and pathogen mediated by NOD2 signaling, might
      provide novel insight into the pathogenesis of pathogenic Mycobacterium and
      inform the development of more effective vaccines and therapeutics.

PMID- 22986286
TI  - Overweight is associated with airflow obstruction and poor disease control but
      not with exhaled nitric oxide change in an asthmatic population.
AB  - BACKGROUND: The role of an elevated body mass index (BMI) in asthma remains
      controversial. OBJECTIVES: To investigate the relationship between overweight
      (BMI >25 and <=30), lung function, disease control, and airway inflammation in an
      asthmatic population. METHODS: We consecutively studied 348 patients (age 43 +/-
      16 years; 211 females). In all patients, BMI, spirometry, the Asthma Control Test
      (ACT), and fractional exhaled nitric oxide (FeNO; ppb) were measured. RESULTS:
      One hundred forty-five patients were overweight and, as compared to those with
      normal BMI, had lower values of FVC, FEV(1), and FEV(1)/FVC and of FEF(25-75)
      even when normalized for FVC (p < 0.05 for each comparison). The ratio between
      the number of patients with well-controlled asthma (ACT >=20) and that of
      patients with poorly controlled asthma (ACT < 20) was significantly lower in
      overweight patients (1.07 vs. 1.84; chi(2) = 6.030, p < 0.01). In overweight
      patients, the odds ratio of uncontrolled asthma expressed by logistic regression
      analysis was 1.632 (95% CI = 1.043-2.553), independently of gender, atopy,
      smoking habit, and inhaled steroid therapy. No difference was observed in FeNO
      values between overweight and normal weight patients (27.7 +/- 2.3 vs. 27.9 +/-
      2.2 ppb). CONCLUSIONS: Our results show that, in an asthmatic population,
      overweight is associated with airflow obstruction and poor disease control but
      not with FeNO change. The findings of the present study support the view that
      other factors besides airway inflammation alone may explain the relationship
      between asthma and an elevated BMI.

PMID- 22986287
TI  - Photoplethysmogram signal quality estimation using repeated Gaussian filters and
      cross-correlation.
AB  - Pulse oximeters are monitors that noninvasively measure heart rate and blood
      oxygen saturation (SpO2). Unfortunately, pulse oximetry is prone to artifacts
      which negatively impact the accuracy of the measurement and can cause a
      significant number of false alarms. We have developed an algorithm to segment
      pulse oximetry signals into pulses and estimate the signal quality in real time.
      The algorithm iteratively calculates a signal quality index (SQI) ranging from 0
      to 100. In the presence of artifacts and irregular signal morphology, the
      algorithm outputs a low SQI number. The pulse segmentation algorithm uses the
      derivative of the signal to find pulse slopes and an adaptive set of repeated
      Gaussian filters to select the correct slopes. Cross-correlation of consecutive
      pulse segments is used to estimate signal quality. Experimental results using two
      different benchmark data sets showed a good pulse detection rate with a
      sensitivity of 96.21% and a positive predictive value of 99.22%, which was
      equivalent to the available reference algorithm. The novel SQI algorithm was
      effective and produced significantly lower SQI values in the presence of
      artifacts compared to SQI values during clean signals. The SQI algorithm may help
      to guide untrained pulse oximeter users and also help in the design of advanced
      algorithms for generating smart alarms.

PMID- 22986290
TI  - Outcome of giant cell arteritis of the arm arteries managed with medical
      treatment alone: cross-sectional follow-up study.
AB  - OBJECTIVE: To assess the long-term outcome of GCA of the arm arteries under
      medical treatment alone. METHODS: Retrospective cross-sectional study of 34
      patients with a diagnosis of GCA involving the arm arteries (i.e. subclavian,
      axillary and/or brachial arteries). All patients were managed with
      immunosuppressive treatment and antiplatelet agents and followed clinically and
      with colour duplex sonography. Characteristics of patients with and without
      relief of ischaemic upper extremity symptoms during follow-up were compared using
      Fisher's exact test and the Mann-Whitney U-test. RESULTS: Sixteen of 34 patients
      (47.1%) suffered from arm claudication at the time of diagnosis (bilateral
      symptoms in 8 patients). During a mean follow-up of 21.9 (17.1) months, none of
      the patients developed new ischaemic symptoms of the upper extremities, and five
      patients became asymptomatic. Critical limb ischaemia did not occur. Symptom
      relief was significantly less frequent in patients with symptomatic ischaemia of
      the right arm vs the left arm and was negatively associated with the presence of
      anaemia and subclavian artery involvement (all P < 0.05). In 32.4% of patients,
      the vasculitic wall thickening, as depicted by colour duplex sonography,
      completely disappeared. CONCLUSION: With medical treatment alone, the prognosis
      of GCA of the arm arteries is benign. Patients with unilateral left-sided
      ischaemic symptoms may have a higher probability of complete symptom relief than
      patients with right-sided or bilateral arm claudication.

PMID- 22986289
TI  - Traditional cardiovascular risk factors, inflammation and cardiovascular risk in
      rheumatoid arthritis.
AB  - Multiple studies demonstrate an increased cardiovascular (CV) risk associated
      with RA compared with the general population. While part of this risk appears to
      be mediated by RA-specific factors, such as long-term inflammation, traditional
      CV comorbidities also play an important role. We review evidence from previous
      studies of the relationship between RA and traditional CV comorbidities such as
      dyslipidaemia, obesity, insulin resistance and diabetes, hypertension, cigarette
      smoking and physical inactivity. We examine the prevalence and consider the
      effect of inflammation and RA treatments on these risk factors. Finally, we
      discuss three widely used CV risk estimators, the Framingham Risk Score, Reynolds
      Risk Score and the Systematic Coronary Risk Evaluation, and their performance in
      patients with RA. The traditional CV risk factors that appear to differ
      significantly between RA cases and controls include insulin resistance, abnormal
      fat distribution, cigarette smoking and lack of physical activity. Dyslipidaemia,
      diabetes and hypertension may also be elevated in RA; however, the evidence is
      conflicting. Overall, we found that the majority of information regarding CV risk
      factors in RA stems from data collected as covariates for studies on CV disease.
      A gap in knowledge exists regarding detailed information on individual risk
      factors in RA, their prevalence and modifications that occur as a result of
      inflammation or treatment. More studies are needed to develop methods for
      accurate CV risk estimation in RA.

PMID- 22986291
TI  - Three new sesquiterpenes from Tithonia diversifolia and their anti-hyperglycemic
      activity.
AB  - Three new germacrane sesquiterpenes (1), (2), (3), along with eleven known
      sesquiterpenes, namely, tirotundin-3-O-methyl ether (4), deacetylvguiestin (5),
      1beta-hydroxydiversifolin-3-O-methyl ether (6), tagitinin C (7), 1beta
      hydroxytirotundin-3-O-methyl ether (8), 1beta-hydroxytirotundin-1,3-O-dimethyl
      ether (9), tagitinin F-3-O-methyl ether (10), tagitinin F (11), tagitinin A (12),
      3beta-acetoxy-4alpha-hydroxyeduesm-11(13)-en-12-oic acid (13) and ilicic acid
      (14) were isolated from the aerial parts of Tithonia diversifolia. Their
      structures were established by spectroscopic analysis, while the relative
      configuration of compound 1 was confirmed by X-ray diffraction analysis. In
      addition, compounds 1-14 were evaluated in vitro for their anti-hyperglycemic
      activity by glucose uptake in 3T3-L1 adipocytes. It was found that 10MUg/mL 1, 3,
      6 and 8 could significantly increase glucose uptake without significant toxic
      effects.

PMID- 22986293
TI  - New flavane gallates isolated from the leaves of Plicosepalus curviflorus and
      their hypoglycemic activity.
AB  - Two new flavane gallates were isolated from the leaves of Plicosepalus
      curviflorus. The structure of the new compounds was established as 2S,3R
      3,3',4',5,7-pentahydroxyflavane-5-O-gallate (1) and 2S,3R-3,3',4',5,5',7
      hexahydroxyflavane-4',5-di-O-gallate (2), respectively. In addition, seven known
      compounds (-)-catechin (3), quercetin (4), lupeol (5), beta-sitosterol (6),
      pomolic acid (7), beta-sitosterol 3-O-beta-d-glucopyranoside (8) and 4
      methoxycinnamic acid (9) were reported for the first time from the genus
      Plicosepalus. Compounds 1, 2 and 3 were investigated for their hypoglycemic
      activity and showed significant hypoglycemic activity in Swiss Albino mice.

PMID- 22986292
TI  - Sesquiterpenes from the aerial part of Chloranthus japonicus and their
      cytotoxicities.
AB  - Four new sesquiterpenes, chlorajapolides F-I (1-4), along with nine known
      terpenoids (5-13) were isolated from the aerial part of Chloranthus japonicus.
      Their structures were elucidated on the basis of spectroscopic analysis, and a
      lindenane sesquiterpene, named 9-hydroxy-heterogorgiolide, previously isolated
      from the C. japonicus, was revised as its 8-epimer (1a). Moreover, methanol
      extract (ME), EtOAc fraction (EF), water fraction (WF), and all isolates (1a, 1
      13) were evaluated for their cytotoxicities using two human cancer cell lines.

PMID- 22986288
TI  - Lysophospholipid receptor activation of RhoA and lipid signaling pathways.
AB  - The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid
      (LPA) signal through G-protein coupled receptors (GPCRs) which couple to multiple
      G-proteins and their effectors. These GPCRs are quite efficacious in coupling to
      the Galpha(12/13) family of G-proteins, which stimulate guanine nucleotide
      exchange factors (GEFs) for RhoA. Activated RhoA subsequently regulates
      downstream enzymes that transduce signals which affect the actin cytoskeleton,
      gene expression, cell proliferation and cell survival. Remarkably many of the
      enzymes regulated downstream of RhoA either use phospholipids as substrates (e.g.
      phospholipase D, phospholipase C-epsilon, PTEN, PI3 kinase) or are regulated by
      phospholipid products (e.g. protein kinase D, Akt). Thus lysophospholipids signal
      from outside of the cell and control phospholipid signaling processes within the
      cell that they target. Here we review evidence suggesting an integrative role for
      RhoA in responding to lysophospholipids upregulated in the pathophysiological
      environment, and in transducing this signal to cellular responses through effects
      on phospholipid regulatory or phospholipid regulated enzymes. This article is
      part of a Special Issue entitled Advances in Lysophospholipid Research.

PMID- 22986294
TI  - Function and structure in social brain regions can link oxytocin-receptor genes
      with autistic social behavior.
AB  - Difficulties in appropriate social and communicative behaviors are the most
      prevalent and core symptoms of autism spectrum disorders (ASDs). Although recent
      intensive research has focused on the neurobiological background of these
      difficulties, many aspects of them were not yet elucidated. Recent studies have
      employed multimodal magnetic resonance imaging (MRI) indices as intermediate
      phenotypes of this behavioral phenotype to link candidate genes with the autistic
      social difficulty. As MRI indices, functional MRI (fMRI), structural MRI, and MR
      spectroscopy have been examined in subjects with autism spectrum disorders. As
      candidate genes, this mini-review has much interest in oxytocin-receptor genes
      (OXTR), since recent studies have repeatedly reported their associations with
      normal variations in social cognition and behavior as well as with their
      extremes, autistic social dysfunction. Through previous increasing studies,
      medial prefrontal cortex, hypothalamus and amygdala have repeatedly been revealed
      as neural correlates of autistic social behavior by MRI multimodalities and their
      relationship to OXTR. For further development of this research area, this mini
      review integrates recent accumulating evidence about human behavioral and neural
      correlates of OXTR.

PMID- 22986295
TI  - Campylobacter sequence typing databases: applications and future prospects.
AB  - Human campylobacteriosis, caused by the zoonotic bacteria Campylobacter jejuni
      and Campylobacter coli, remains a major cause of gastroenteritis worldwide. For
      many countries the implementation of effective interventions to reduce the burden
      of this disease is a high priority. Nucleotide sequence-based typing, including
      multilocus sequence typing (MLST) and antigen gene sequence typing (AGST), has
      provided unified, comprehensive, and portable Campylobacter isolate
      characterization, with curated databases of genotypes available
      (pubMLST.org/campylobacter). Analyses of large collections of isolates from
      various sources with these approaches have provided many insights into the
      epidemiology of these ubiquitous and diverse organisms. C. jejuni and C. coli
      populations are structured into clonal complexes, which reflect genealogy and are
      associated with specific phenotypes, e.g. the predisposition to infect particular
      animals, a property that has permitted the development of genetic means of
      attributing isolates from human disease to potential sources. This has identified
      retail meat, and especially chicken, as the likely cause of most human disease in
      many countries, although some human isolates have other likely origins. Such data
      have led directly to effective intervention studies and will be important in
      ongoing targeting of intervention strategies and the monitoring of their
      effectiveness. MLST and AGST data have also been employed in epidemiological
      investigations and studies of Campylobacter evolution and population biology. The
      sequence databases that have been established are compatible with the whole
      genome sequencing (WGS) approaches likely to be implemented soon; indeed, the
      hierarchical approach adopted by MLST and AGST will be essential for the
      exploitation of WGS data.

PMID- 22986296
TI  - The effect of intra-articular injection of microRNA-210 on ligament healing in a
      rat model.
AB  - BACKGROUND: It is known from clinical and experimental studies that the healing
      potential of the anterior cruciate ligament (ACL) is extremely poor and that
      early phases of ligament healing require an augmented blood supply. MicroRNA
      (miRNA) is a type of small, noncoding RNA that negatively regulates gene
      expression, and miRNA (miR)-210 is reported to be crucial for cell response to
      hypoxia, vascular endothelial growth factor (VEGF)-driven endothelial cell
      migration, and formation of capillary-like structures. PURPOSE: The purpose of
      this study was to examine the effect of intra-articular injection of miRNA miR
      210 on acceleration of ACL healing. STUDY DESIGN: Controlled laboratory study.
      METHODS: Two experiments were performed in this study. The ACLs of 12-week-old
      male LEW/CrlCrlj rats were partially transected. First, the temporal expression
      change of miR-210 after ACL injury was analyzed using real-time polymerase chain
      reaction (PCR) on day zero, and 1, 2, and 4 weeks after injury (n = 5 at each
      time point). Next, intra-articular injection of double-stranded (ds) miR-210 with
      atelocollagen was performed soon after injury. The control group was injected
      with control small interfering RNA (siRNA). Four weeks after injection,
      biomechanical and histological assessments of samples stained with H&E as well as
      Masson trichrome, and immunohistochemistry for VEGF, fibroblast growth factor 2
      (FGF2), isolectin B4, and collagen type I, were performed. Real-time PCR analysis
      was also performed for quantitative evaluation of miR-210, VEGF-A, and collagen
      type I. RESULTS: Real-time PCR analysis revealed that miR-210 expression was
      decreased soon after injury but gradually increased thereafter. Histological
      analysis confirmed that the transected area was covered with healing tissue in
      the miR-210 group but remained devoid of any tissue in the control group 4 weeks
      after injury. Biomechanical analysis confirmed the improvement of biomechanical
      properties in the miR-210 group; the ultimate failure loads 4 weeks after
      injection were 30.5 +/- 3.1 N in the miR-210 group and 22.8 +/- 3.1 N in the
      control group (P < .05). Real-time PCR analysis showed that endogenous miR-210,
      VEGF, and collagen type I were highly expressed compared with controls, and
      immunohistochemistry for VEGF, FGF2, isolectin B4, and collagen type I showed
      that VEGF and FGF2 were highly upregulated, and there were abundant blood vessels
      and fibrotic deposition in the miR-210 group. CONCLUSION: Injection of ds miR-210
      was effective in promoting the healing of partially torn ACLs through enhancement
      of angiogenesis via upregulation of VEGF and FGF2. CLINICAL RELEVANCE: It might
      represent a potential therapeutic approach for treatment of ACL injury.

PMID- 22986297
TI  - Return-to-play outcomes after microscopic lumbar diskectomy in professional
      athletes.
AB  - BACKGROUND: It has been shown a microscopic lumbar diskectomy (MLD) is effective
      in getting professional athletes back to their sport after a herniated nucleus
      pulposus (HNP). There is a need for more information on the time it takes
      professional athletes to return after surgery. PURPOSE: To determine average time
      for return to play and success in returning to play for professional athletes
      undergoing MLD. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between
      1996 and 2010, the senior authors treated 171 professional athletes for lumbar
      HNP. A retrospective review was performed using patient charts, operative
      reports, team medical records, and internet search. Eighty-five patients were
      treated with MLD, and 86 patients were treated nonoperatively. This study focused
      on the return to play of the operatively treated patients. Primary outcome
      measures were return rate and average return time, considering only patients
      whose sport is in season at specific postoperative time points. RESULTS: Of
      surgically treated patients, 89.3% returned to sport. The average time it took
      operative patients to return to their sport (return time) was 5.8 months.
      Progressive return data for surgically treated patients showed the percentage of
      athletes who returned increased from 50% at 3 months to 72% at 6 months to 77% at
      9 months and 84% at 12 months. CONCLUSION: The chance a player returns to play
      after MLD is 50% at 3 months, 72% at 6 months, 77% at 9 months, and 84% at 12
      months. The overall chance of returning to play at any point is 89%.

PMID- 22986298
TI  - Development of a chute to facilitate transvaginal ultrasound guided oocyte
      aspiration (TUGA) in the sow.
AB  - A procedure developed for nonsurgical transvaginal ultrasound-guided oocyte
      aspiration in the mature sow was dependent upon development of a special chute.
      This chute was designed to immobilize and protect the sow. The floor of the chute
      possessed a metal bar that was elevated via a hydraulic lift until the weight of
      the sow rested on the bar, while her hooves were still in contact with the floor.
      This exact positioning of the female prevented her from resisting procedure and
      allowed for a comfortable setting for technician to manipulate the ovaries (per
      rectum) and perform transvaginal ultrasound guided oocyte aspiration (TUGA).
      Oocyte collection was performed in six sows, and none experienced detrimental
      health effects from the procedure.

PMID- 22986299
TI  - Molecular detection of spotted fever group rickettsia in feral raccoons (Procyon
      lotor) in the western part of Japan.
AB  - Rickettsial infection in feral raccoons (Procyon lotor) in the western part of
      Japan (Shimane, Fukuoka, Saga and Nagasaki Prefectures) was surveyed by a nested
      polymerase chain reaction (PCR) assay detecting the rickettsial citrate synthase
      (gltA) gene. Four of one hundred and ninety-four feral raccoon spleens (2.1%)
      were positive for Rickettsia spp. One gltA gene sequence was identical to R.
      helvetica, whereas the other 3 sequences were identical and had the highest
      similarity (98.4%) to R. amblyommii. Simultaneously, we determined a partial
      sequence of the rickettsial 17-kilodalton (17K) genus-common antigen gene in the
      later 3 raccoon samples. Their sequences were identical and had the highest
      similarity (98.5%) to Rickettsia sp. Hj126. Based on the sequences of gltA and
      17K antigen genes, these raccoons might be infected with spotted fever group
      (SFG) rickettsia most closely related to R. amblyommii and/or Rickettsia sp.
      Hj126. Feral raccoons may be a susceptible reservoir for SFG rickettsiae in
      Japan.

PMID- 22986300
TI  - Patent ductus arteriosus ligation in two young cats with pulmonary hypertension.
AB  - We report two feline cases of patent ductus arteriosus (PDA) with pulmonary
      hypertension (PH). The subjects were both intact domestic shorthair cats, a 4
      month-old, 2.5 kg male (case 1) and an 8-month-old, 2.12 kg female (case 2). At
      the first presentation, left-sided congestive heart failure was diagnosed in case
      1 and severe aortic stenosis (AS) in case 2. Following surgical ligation of the
      ductus arteriosus (DA), furosemide therapy was no longer required in case 1, and
      the severe AS improved to mild status in case 2 perhaps because of reduced volume
      overload. In case 2, severe hypoxemia was revealed after surgery; however, this
      normalized within 96 days after surgery.

PMID- 22986301
TI  - Photoswitching of the second-order nonlinearity of a tetrahedral octupolar multi
      DTE-based copper(I) complex.
AB  - The modulation of the quadratic NLO response of an octupolar metal-based
      chromophore featuring four photochromic dithienylethene units is reported.
      Quantum mechanical simulations are consistent with a full switching of the DTE
      units and reproduce the strong enhancement of the NLO response.

PMID- 22986302
TI  - Combination therapy in pulmonary arterial hypertension.

PMID- 22986303
TI  - Effect of endotracheal tube leak on capnographic measurements in a ventilated
      neonatal lung model.
AB  - Uncuffed endotracheal tubes (ET) are commonly used for mechanically ventilated
      infants to protect airways, but this bears the risk of an air leak around the ET.
      In contrast to the measurements of tidal volume and respiratory mechanics, very
      little is known about the effect of ET leaks on capnographic measurements. To
      investigate the relationship between ET leakage and the CO2 measuring error of
      the exhaled breathing gas a neonatal lung model was used consisting of two
      silicon bellows. A constant but very low flow of pure CO2 was injected so that
      the exhaled breathing gas contained an adjustable CO2 plateau. This lung model
      was ventilated via a 3 mm inner diameter ET with different respiratory rates (RR)
      (20, 40 and 60 min(-1)). ET leaks (0-80%) were simulated by a needle valve. The
      end-expiratory CO2 partial pressure (PetCO2) was reduced up to zero when an air
      leak was simulated. Provided that the exhaled CO2 reached a plateau before
      entering the CO2 washout of the sample chamber by the leak flow, the magnitude of
      the CO2 decreased independently of RR, and only slightly with increasing ET leak.
      For ET leaks of up to 20% the CO2 plateau error was <10%. However, in newborns
      with stiff lungs and a short alveolar plateau capnographic measurements should be
      interpreted with caution if the ET leak is considerable.

PMID- 22986304
TI  - Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits
      lowered sociability and learning impairment.
AB  - Dravet syndrome is an intractable epileptic encephalopathy characterized by early
      onset epileptic seizures followed by cognitive decline, hyperactivity, autistic
      behaviors and ataxia. Most Dravet syndrome patients possess heterozygous
      mutations of SCN1A gene encoding voltage-gated sodium channel alphaI subunit
      (Nav1.1). We have previously reported that mice heterozygous for a nonsense
      mutation in Scn1a developed early onset epileptic seizures. However, the learning
      ability and sociability of the mice remained to be investigated. In the present
      study, we subjected heterozygous Scn1a mice to a comprehensive behavioral test
      battery. We found that while heterozygous Scn1a mice had lowered spontaneous
      motor activity in home cage, they were hyperactive in novel environments.
      Moreover, the mice had low sociability and poor spatial learning ability that
      correspond to the autistic behaviors and cognitive decline seen in Dravet
      syndrome patients. These results suggest that Nav1.1 haploinsufficiency
      intrinsically contributes to not only epileptic seizures but also lowered
      sociability and learning impairment in heterozygous Scn1a mutant mice, as it
      should also be the case in patients with Dravet syndrome. 

PMID- 22986305
TI  - Extraction of tissue antigens for functional assays.
AB  - Many of the antigen targets of adaptive immune response, recognized by B and T
      cells, have not been defined (1). This is particularly true in autoimmune
      diseases and cancer(2). Our aim is to investigate the antigens recognized by
      human T cells in the autoimmune disease type 1 diabetes (1,3,4,5). To analyze
      human T-cell responses against tissue where the antigens recognized by T cells
      are not identified we developed a method to extract protein antigens from human
      tissue in a format that is compatible with functional assays (6). Previously, T
      cell responses to unpurified tissue extracts could not be measured because the
      extraction methods yield a lysate that contained detergents that were toxic to
      human peripheral blood mononuclear cells. Here we describe a protocol for
      extracting proteins from human tissues in a format that is not toxic to human T
      cells. The tissue is homogenized in a mixture of butan-1-ol, acetonitrile and
      water (BAW). The protein concentration in the tissue extract is measured and a
      known mass of protein is aliquoted into tubes. After extraction, the organic
      solvents are removed by lyophilization. Lyophilized tissue extracts can be stored
      until required. For use in assays of immune function, a suspension of immune
      cells, in appropriate culture media, can be added directly to the lyophilized
      extract. Cytokine production and proliferation by PBMC, in response to extracts
      prepared using this method, were readily measured. Hence, our method allows the
      rapid preparation of human tissue lysates that can be used as a source of
      antigens in the analysis of T-cell responses. We suggest that this method will
      facilitate the analysis of adaptive immune responses to tissues in
      transplantation, cancer and autoimmunity.

PMID- 22986306
TI  - Kinetics of D-glucose and D-fructose conversion during the alcoholic fermentation
      promoted by Saccharomyces cerevisiae.
AB  - Although many studies on the different aspects of alcoholic fermentation are
      available in the literature, it is still difficult to identify the possible
      causes of the slowing-down or stuck of fermentations, even if the change of some
      compositional parameters (D-glucose/D-fructose and glycerine produced/hexoses
      converted ratios) could be assumed as sound signals of a possible deviation from
      the usual Saccharomyces metabolic pathways. The reason why alcoholic yeasts
      preferably metabolise D-glucose rather than D-fructose was investigated by a
      kinetic model based on six functional parameters having a well-defined chemical
      physical meaning. The time evolution of different initial concentrations of D
      glucose and D-fructose, dissolved in a model solution simulating a must (citrate
      buffer at pH 3.4 inoculated by a commercial strain of Saccharomyces cerevisiae),
      was investigated adding or not ethanol to the reaction medium. When a reduced
      amount of ethanol was dissolved in the reaction medium, the time evolution of the
      fermentation rates of these two sugars did not differ significantly, to diversify
      rather strongly when the alcoholic concentration increased. The hypothesised
      mathematical model accounts for this particular kinetic behaviour. In fact, only
      the sensitivity to ethanol showed by the enzymatic protein involved in the
      limiting steps of the fermentation process of these two sugars differed
      significantly, the enzymatic transformation of D-fructose being more sensitive to
      ethanol than D-glucose. This difference was able to justify the different kinetic
      behaviours shown by the two sugars when ethanol concentration in the reaction
      medium increased.

PMID- 22986307
TI  - Rapid and simple colorimetric assay for detecting the enzymatic degradation of
      biodegradable plastic films.
AB  - We developed a rapid and simple method for evaluating the degradation of solid
      biodegradable plastics (BPs). Dye-containing BP films were used as substrates and
      the release of dye caused by the degradation of BPs was confirmed by a color
      change in the enzyme solution after a reaction time of 24 h.

PMID- 22986308
TI  - Preparation of a gamma-glutamylcysteine-enriched yeast extract from a newly
      developed GSH2-deficient strain.
AB  - Gamma-glutamylcysteine (gamma-GC), the precursor of glutathione (GSH), may have
      significant health benefits as a dietary supplement, but there are few cost
      effective methods available for its large-scale production. We developed an
      efficient method for producing gamma-GC in a mutant yeast strain using a three
      step breeding procedure and a unique cultivation process. In the first breeding
      step, we prepared a glutathione synthetase (GSH2)-deficient yeast mutant. In the
      second step, selenate (SeO(4)(2-)) sensitivity was introduced by crossing the
      GSH2-deficient mutant with a strain harboring the met30 mutation. In the final
      step, pantothenic acid auxotrophy was introduced by ethyl methanesulfonate
      mutagenesis. The isolated strain displayed significantly enhanced cellular gamma
      GC when cultivated in synthetic medium without pantothenic acid, reaching a
      maximum level of 4.39% of dry cell weight. Using this strain, we were able to
      prepare a yeast extract containing approximately 13% gamma-GC (w/w), which is
      markedly higher than the reported value (0.3%) of commercially available yeast
      extracts. The present method may facilitate large-scale gamma-GC production for
      investigating the nutritive value and other benefits of dietary gamma-GC.

PMID- 22986309
TI  - Reaction of o-carboranes with sterically demanding N-heterocyclic carbene:
      synthesis and structural characterization of 1 : 1 adducts.
AB  - Several nido-carborane-carbene 1 : 1 adducts were prepared in very high yields
      from the reaction of o-carboranes with 1,3-bis(2,6-diisopropylphenyl)imidazol-2
      ylidene in dry THF at room temperature. Single-crystal X-ray analyses reveal that
      they are zwitterionic salts consisting of a nido carborane cage and imidazolium
      moiety that are linked by a five-coordinate boron atom. They are inert toward
      carbenes, but sensitive toward moisture and water, leading to the formation of
      deboration products, nido-C(2)B(9) ions. These results shed light on the
      deboration reaction mechanism of o-carboranes.

PMID- 22986310
TI  - Crohn's disease: Cell transplant stems IBD.

PMID- 22986311
TI  - Oesophageal cancer: A surface maturation score to diagnose oesophageal squamous
      cell intraepithelial neoplasia.

PMID- 22986312
TI  - Somatostatin receptor types 1 and 2 in the developing mammalian cochlea.
AB  - The neuropeptide somatostatin (SST) exerts several important physiological
      actions in the adult central nervous system through interactions with membrane
      bound receptors. Transient expression of SST and its receptors has been described
      in several brain areas during early ontogeny. It is therefore believed that SST
      may play a role in neural maturation. The present study provides the first
      evidence for the developmental expression of SST receptors in the mammalian
      cochlea, emphasizing their possible roles in cochlear maturation. In the
      developing mouse cochlea, cells immunoreactive to somatostatin receptor 1 (SSTR1)
      and somatostatin receptor 2 (SSTR2) were located in the embryonic cochlear duct
      on Kolliker's organ as early as embryonic day (E) 14 (E14). At E17, the
      expression of both receptors was high and already located at the hair cells and
      supporting cells along the length of the cochlear duct, which have become
      arranged into the characteristic pattern for the organ of Corti (OC) at this
      stage. At birth, SSTR1- and SSTR2-containing cells were only localized in the OC.
      In general, immunoreactivity for both receptors increased in the mouse cochlea
      from postnatal day (P) 0 (P0) to P10; the majority of immunostained cells were
      inner hair cells, outer hair cells, and supporting cells. Finally, a peak in the
      mRNA and protein expression of both receptors is present near the time when they
      respond to physiological hearing (i.e., hearing of airborne sound) at P14. At
      P21, SSTR1 and SSTR2 levels decrease dramatically. A similar developmental
      pattern was observed for SSTR1 and SSTR2 mRNA, suggesting that the expression of
      the SSTR1 and SSTR2 genes is controlled at the transcriptional level throughout
      development. In addition, we observed reduced levels of phospho-Akt and total Akt
      in SSTR1 knockout and SSTR1/SSTR2 double-knockout mice compared with wild-type
      mice. We know from previous studies that Akt is involved in hair cell survival.
      Taken together, the dynamic nature of SSTR1 and SSTR2 expression at a time of
      major developmental changes in the cochlea suggests that SSTR1 and SSTR2 (and
      possibly other members of this family) are involved in the maturation of the
      mammalian cochlea.

PMID- 22986313
TI  - Characterization of the cardiac ganglion in the crab Neohelice granulata and
      immunohistochemical evidence of GABA-like extrinsic regulation.
AB  - The aim of the present work is to provide an anatomical description of the
      cardiac system in the crab Neohelice granulata and evidence of the presence of
      GABA by means of immunohistochemistry. The ganglionic trunk was found lying on
      the inner surface of the heart's dorsal wall. After dissection, this structure
      appeared as a Y-shaped figure with its major axis perpendicular to the major axis
      of the heart. Inside the cardiac ganglion, we identified four large neurons of
      63.7 MUm +/- 3.7 in maximum diameter, which were similar to the motor neurons
      described in other decapods. All the GABA-like immunoreactivity (GABAi) was
      observed as processes entering mainly the ganglionic trunk and branching in
      slender varicose fibers, forming a network around the large neurons suggesting
      that GABAi processes contact them. Our findings strengthen previous results
      suggesting that the GABAergic system mediates the cardio-inhibitory response upon
      sensory stimulation.

PMID- 22986314
TI  - The risk of injury to the anterior tibial artery in the posterolateral approach
      to the tibia plateau: a cadaver study.
AB  - BACKGROUND: Posterolateral tibial plateau shear fractures often require buttress
      plating, which can be performed through a posterolateral approach. The purpose of
      this study was to provide accurate data about the inferior limit of dissection.
      METHODS: Forty unpaired cadaver adult lower limbs were used. The anterior tibial
      artery was identified because it coursed through the interosseous membrane. The
      perpendicular distance from the lateral joint line and fibula head to this
      landmark was measured. RESULTS: The anterior tibial artery coursed through the
      interosseous membrane at 46.3 +/- 9.0 mm (range 27-62 mm) distal to the lateral
      tibial plateau and 35.7 +/- 9.0 mm (range 17-50 mm) distal to the fibula head.
      CONCLUSIONS: Displaced posterolateral tibial plateau fractures require anatomic
      reduction and stabilization with a buttress plate. This can be achieved by
      gaining access to the posterolateral tibial cortex. The distal limit of this
      dissection can be as little as 27 mm distal to the lateral tibial plateau.
      Dissection in this region should be carried out with caution.

PMID- 22986315
TI  - Surgical treatment improves clinical and functional outcomes for patients who
      sustain incomplete bisphosphonate-related femur fractures.
AB  - OBJECTIVE: To describe the outcomes for patients treated at a single institution,
      who sustained incomplete bisphosphonate-induced femoral fractures. DESIGN:
      Retrospective review. SETTING: University-based academic medical center.
      PATIENTS: Thirty-one patients with 43 incomplete fractures met the inclusion
      criteria. INTERVENTION: Nonoperative management or surgical intervention for
      fractures with refractory symptoms or progression of fracture lucency on
      radiographs. MAIN OUTCOME MEASUREMENTS: Radiographic assessments and the Short
      Musculoskeletal Functional Assessment to gauge functional status. RESULTS: The
      cohort was all women with an average age of 69.2 (range: 46-92) years and had
      been treated with bisphosphonate therapy for an average of 9.1 (range: 5-20)
      years. The average healing time for all incomplete fractures was 9.4 (range: 1.5
      36) months. Forty-nine percent of the fractures (21 of 43 fractures) were
      ultimately treated with surgery for impending complete fracture or failure of
      nonsurgical management. Of the incomplete fractures treated with surgery, 81%
      became pain free and 100% were radiographically healed at a mean of 7.1 (range:
      1.5-12) months. In contrast, of the nonoperatively treated incomplete fractures,
      only 64% were pain free at latest follow-up, with only 18% of fractures
      demonstrating radiographic evidence of healing at an average of 11 (range: 6-24)
      months. Standardized dysfunction index from the Short Musculoskeletal Functional
      Assessment was better (19.7) in the surgical group than in the nonsurgical group
      (19.7 vs. 25.7, P = 0.0017). CONCLUSIONS: A higher percentage of patients treated
      surgically became asymptomatic and demonstrated radiographic evidence of healing
      earlier than those treated nonsurgically. Surgical intervention is effective for
      relief of symptoms when treating incomplete bisphosphonate-related femur
      fractures, and patients should be counseled to the potential benefits of
      prophylactic surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 22986316
TI  - Reducing postoperative ileus: does the anesthetic technique matter?

PMID- 22986317
TI  - Transmylohyoid orotracheal intubation: case series and review.
AB  - STUDY OBJECTIVE: To evaluate the outcome of airway management in patients with
      complex maxillofacial fracture by submental intubation, time required for
      intubation, accidental extubation, and postoperative complications. DESIGN:
      Retrospective study. SETTING: University-affiliated hospital. MEASUREMENTS: The
      medical records of the 10 patients who underwent submental intubation from
      December 2008 to June 2011 were reviewed. MAIN RESULTS: At the end of the
      procedure, all 10 patients were extubated without any complications.
      Postoperatively, only one patient presented with superficial infection of the
      submental wound. CONCLUSIONS: Submental endotracheal intubation is a simple
      technique with very low morbidity, and may be used as an alternative to
      tracheostomy in selected cases of maxillofacial trauma.

PMID- 22986318
TI  - Intraoperative intravenous lidocaine reduces hospital length of stay following
      open gastrectomy for stomach cancer in men.
AB  - STUDY OBJECTIVE: To evaluate whether intraoperative low-dose lidocaine infusion
      decreases postoperative analgesic consumption, ileus, and duration of hospital
      stay. DESIGN: Prospective, randomized, double-blinded trial. SETTING: Operating
      room in a university hospital. PATIENTS: 48 ASA physical status 1 and 2 men
      scheduled for subtotal gastrectomy. INTERVENTIONS: Patients were randomly
      allocated to two groups to receive either intravenous (IV) lidocaine 1.5 mg/kg 20
      minutes before incision followed by a continuous lidocaine infusion of 1.5
      mg/kg/hr until the end of surgery (lidocaine group) or saline in a similar manner
      (control group). MEASUREMENTS: Outcomes such as pain intensity, postoperative
      analgesic consumption, duration of ileus, and hospital length of stay (LOS) were
      recorded. MAIN RESULTS: There were no differences in total consumption of IV
      patient-controlled analgesia (IVPCA) or pain scores at 24, 48, or 72 hours
      postoperatively. However, lidocaine group patients had significantly decreased
      average supplemental pethidine requirement per patient for pain control until 72
      hours postoperatively [150 (75-200) mg vs 50 (50-150) mg, P = 0.039] and hospital
      LOS (9.5 +/- 3 d vs 8.7 +/- 1 d, P = 0.006, 95% CI: - 0.3 - 1.9 d) than control
      group patients. However, no differences were noted between the groups in pain
      intensity or duration of ileus. CONCLUSIONS: Intraoperative IV low-dose lidocaine
      infusion decreased opioid consumption and hospital LOS after gastrectomy.

PMID- 22986319
TI  - Preoperative exercise heart rate recovery predicts intraoperative hypotension in
      patients undergoing noncardiac surgery.
AB  - STUDY OBJECTIVE: To assess the predictive role of heart rate (HR) recovery in the
      detection of intraoperative hypotension in patients undergoing noncardiac
      surgery. DESIGN: Prospective, observational study. SETTING: Department of
      cardiology and operating rooms of university hospitals. PATIENTS: 160 ASA
      physical status 1 and 2 patients scheduled for elective noncardiac surgery.
      MEASUREMENTS: All patients underwent exercise stress testing. Maximum HRs and
      metabolic equivalent levels were recorded. Heart rate recovery at the first,
      second, and third minutes were calculated by subtracting HRs one, two, and three
      minutes into the recovery period from the maximal HR at peak exercise. A decrease
      in mean arterial pressure (MAP) of greater than 30% was defined as intraoperative
      hypotension and recorded. Patients were classified to two groups according to
      whether they had intraoperative hypotension. MAIN RESULTS: Hypotensive episode
      was observed in 31 patients (19.7%) during the operation. The presence of
      diabetes mellitus was higher in patients with intraoperative hypotension (22.6%
      vs 7.1%, P = 0.019). Mean HR recovery at the first, second, and third minutes was
      significantly lower in the intraoperative hypotension group (P = 0.001, P =
      0.004, and P = 0.031, respectively). Heart rate recovery at the first, second,
      and third minutes was a good predictor of intraoperative hypotension, but only HR
      recovery at the first minute (OR 0.82, 95% CI 0.73 to 0.92, P = 0.001) and HR
      recovery at the second minute (OR, 0.90; 95% CI, 0.82 to 0.98; P = 0.019) were
      independent predictors of intraoperative hypotension. A higher negative
      correlation was noted between the degree of MAP reduction and HR recovery at the
      first minute (r = -0.797, P = 0.001). CONCLUSIONS: Abnormal preoperative exercise
      HR recovery predicts intraoperative hypotension in patients undergoing noncardiac
      surgery. Given the importance of intraoperative hypotension, preoperative use of
      exercise testing might be considered.

PMID- 22986320
TI  - Anesthetic considerations for robotic prostatectomy: a review of the literature.
AB  - Since the first robotic prostatectomy in 2000, the number of prostatectomies
      performed using robot-assisted laparoscopy has been increasing. As of 2009,
      90,000 robotic radical prostatectomies were performed worldwide, and 80% of all
      radical prostatectomies performed in the United States were performed
      robotically. Robotic prostatectomy is becoming more common globally because of
      the many advantages offered to patients, primarily due to the minimally invasive
      nature of the procedure. Several new perioperative concerns and challenges for
      anesthesiologists and are described.

PMID- 22986321
TI  - Abnormal coagulation parameters in thawed frozen plasma.

PMID- 22986322
TI  - An infant with aortoiliac thrombosis due to congenital protein C deficiency:
      anesthetic implications.

PMID- 22986323
TI  - Sinus arrest during insertion of a Laryngeal Mask Airway.

PMID- 22986325
TI  - Epidural hematoma at skull pin fixation sites may cause refractory intraoperative
      brain bulge.

PMID- 22986324
TI  - Pulmonary embolism after administration of recombinant activated Factor VII for
      major obstetric hemorrhage.

PMID- 22986326
TI  - Methylene blue treatment for vasoplegia and resultant isoelectric processed EEG
      (bispectral index).

PMID- 22986328
TI  - Does Huntington's disease enhance cephalad spread during neuraxial anesthesia for
      cesarean section?

PMID- 22986327
TI  - Cases of esophageal syncope in the early postoperative period.

PMID- 22986329
TI  - Making the case for obstetric "response teams" and simulation in labor and
      delivery: management of catastrophic amniotic fluid embolism during labor.

PMID- 22986330
TI  - Subacute spinal subarachnoid hematoma following combined spinal-epidural
      anesthesia treated conservatively: a case report.

PMID- 22986331
TI  - Genetic variants in epoxide hydrolases modify the risk of oligozoospermia and
      asthenospermia in Han-Chinese population.
AB  - OBJECTIVES: Epoxide hydrolases are involved in detoxifying and excreting the
      environmental chemicals, which are associated with decreased semen quality and
      male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be
      associated with risk of oligozoospermia and asthenospermia. DESIGN AND METHODS:
      In this study, 468 fertile controls and 672 idiopathic male infertile patients
      were recruited. SNPstream and TaqMan assay were used to genotype four single
      nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by
      computer-assisted semen analysis system. RESULTS: Our results demonstrated that
      rs1042064 of EPHX2 was significantly associated with decreased risk of
      oligozoospermia (OR=0.65, 95% CI: 0.44-0.98) and asthenospermia (OR=0.66, 95% CI:
      0.46-0.94). CONCLUSIONS: Our results provided evidence that genetic variants in
      epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in
      Han-Chinese population.

PMID- 22986332
TI  - Characterization of cytochrome P450 monooxygenases isolated from trichome
      enriched fraction of Artemisia annua L. leaf.
AB  - CYPs have major role in the biosynthesis and modification of secondary
      metabolites. Predicting the possible involvement of CYPs in secondary metabolism,
      20 partial sequences were amplified from the cDNA of trichome enriched tissue of
      Artemisia annua. Seven CYPs were converted to full length and assigned to
      different families based on sequence homology. These were co-expressed with CPR
      in Saccharomyces cerevisiae and microsome fractions were assayed for conversion
      of sesquiterpenes, phenols and fatty acid substrates. CIM_CYP02(c73) and
      CIM_CYP05(c81) converted trans-cinnamic acid to p-coumaric acid; and capric acid,
      lauric acid to their hydroxylated products, respectively. Higher expression of
      CIM_CYP71AV1, CIM_CYP03(c72a), CIM_CYP06(c72b), CIM_CYP02(c73) and CIM_CYP04(c83)
      was observed in the mature leaf, whereas expression of CIM_CYP05(c81) was more in
      the seedling. CIM_CYP71AV1, CIM_CYP02(c73) and CIM_CYP04(c83) expressed more in
      the flower bud compared to the leaf, with minor expression in stem. All CYPs'
      expression increased progressively with time after wounding except for
      CIM_CYP07(c92). These results relate involvement of CIM_CYP02(c73) to phenyl
      propanoid metabolism in the leaf and CIM_CYP05(c81) to fatty acid metabolism in
      the seedling. Expression of CIM_CYP71AV1 and CIM_CYP02(c73) significantly
      increased when sprayed with trans-cinnamic acid indicating a relationship between
      phenylpropanoid and artemisinic acid pathways.

PMID- 22986333
TI  - Identification and expression analysis of NADH-cytochrome b5 reductase gene in
      the cotton bollworm, Helicoverpa armigera.
AB  - NADH-cytochrome b(5) reductase (CBR) is one of the most important components of
      cytochrome P450s, which play an essential role in the detoxification of
      xenobiotics as well as insecticide resistance in insect pest. In the present
      study, two novel full-length cDNAs of CBR of the cotton bollworm, Helicoverpa
      armigera (Hubner) were amplified by means of reverse transcription-polymerase
      chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) techniques.
      The sequencing results showed that the transcripts were 1809bp and 1518bp for
      HaCBR1 and HaCBR2, respectively, including 969bp and 939bp of complete open
      reading frame (ORF), which encoded 322 and 312 amino acids respectively. The
      putative structure and function of HaCBR1 and HaCBR2 were preliminarily analyzed
      by SMART program. HaCBR1 and HaCBR2 (GenBank accession numbers: HQ638220 and
      HQ190046HQ638220HQ190046) showed high identities with CBRs of other species. The
      expression of HaCBR1 and HaCBR2 mRNA was detected by real-time quantitative
      polymerase chain reaction (RT-qPCR) in most developmental stages of H. armigera
      with the exception of eggs, as well as in tissues such as cuticle, fatbody and
      midgut. The expression level of the two genes was significantly induced by
      phenobarbital (PB). These results would contribute to the understanding of CBR
      function in H. armigera and provide information for further study on the
      interactions of different components of cytochrome P450 enzyme systems.

PMID- 22986334
TI  - Serum VEGF levels as predictive marker of bisphosphonate-related osteonecrosis of
      the jaw.
AB  - Recent studies have been reported that angiogenesis suppression may play a role
      in developing bisphosphonate-related osteonecrosis of the jaw (B-ONJ). According
      to these evidence we evaluated the role of VEGF as predictive marker of B-ONJ
      onset. Of the 81 patients, 6 developed B-ONJ following bisphosphonate treatment.
      These patients showed a strongest decrease in VEGF circulating levels at day 7
      and at day 21 after the first administration. These data demonstrated for the
      first time that the anti-angiogenic properties of bisphosphonates are directly
      linked to B-ONJ pathogenesis and serum VEGF levels could represent an effective
      early predictive marker.

PMID- 22986335
TI  - Acute stress-induced sensitization of the pituitary-adrenal response to
      heterotypic stressors: independence of glucocorticoid release and activation of
      CRH1 receptors.
AB  - A single exposure to some severe stressors causes sensitization of the
      hypothalamic-pituitary-adrenal (HPA) response to novel stressors. However, the
      putative factors involved in stress-induced sensitization are not known. In the
      present work we studied in adult male rats the possible role of glucocorticoids
      and CRH type 1 receptor (CRH-R1), using an inhibitor of glucocorticoid synthesis
      (metyrapone, MET), the glucocorticoid receptor (GR) antagonist RU38486
      (mifepristone) and the non-peptide CRH-R1 antagonist R121919. In a first
      experiment we demonstrated with different doses of MET (40-150 mg/kg) that the
      highest dose acted as a pharmacological stressor greatly increasing ACTH release
      and altering the normal circadian pattern of HPA hormones, but no dose affected
      ACTH responsiveness to a novel environment as assessed 3 days after drug
      administration. In a second experiment, we found that MET, at a dose (75 mg/kg)
      that blocked the corticosterone response to immobilization (IMO), did not alter
      IMO-induced ACTH sensitization. Finally, neither the GR nor the CRH-R1
      antagonists blocked IMO-induced ACTH sensitization on the day after IMO. Thus, a
      high dose of MET, in contrast to IMO, was unable to sensitize the HPA response to
      a novel environment despite the huge activation of the HPA axis caused by the
      drug. Neither a moderate dose of MET that markedly reduced corticosterone
      response to IMO, nor the blockade of GR or CRH-R1 receptors was able to alter
      stress-induced HPA sensitization. Therefore, stress-induced sensitization is not
      the mere consequence of a marked HPA activation and does not involve activation
      of glucocorticoid or CRH-R1 receptors.

PMID- 22986336
TI  - Oral contraceptive usage alters the effects of cortisol on implicit fear
      learning.
AB  - An important feature of the human defense system comprises fear learning, which
      stress hormones can crucially modulate. However, stress hormones might influence
      men and women differently, in part because of interactions with sex hormones. In
      women, distinct stages of the menstrual cycle or the intake of oral
      contraceptives (OC) affect sex hormone levels. In this study, we used a
      differential fear conditioning paradigm with electrical stimulation as
      unconditioned stimulus (UCS) following one neutral stimulus (conditioned
      stimulus, CS+), but not another (CS-).To investigate implicit fear learning,
      participants were distracted from detecting the contingencies between CS and UCS.
      To address interaction effects of sex and stress hormones, 32 men, 30 women in
      the early follicular phase of the menstrual cycle (FO), 30 women in the luteal
      phase (LU), and 30 OC women received either 30 mg cortisol or a placebo. In the
      contrast CS+ minus CS-, an interaction between cortisol administration and sex
      hormone status emerged in the anterior parahippocampal gyrus and the hippocampus.
      Cortisol reduced fear learning in men, FO, and LU women, but enhanced it in OC
      women. Additionally, cortisol attenuated differential amygdala activation in the
      entire group. These results demonstrate that OC usage substantially modifies
      cortisol effects on emotional learning in women, particularly in memory-related
      medial temporal lobe regions. Further, a high dose of cortisol reduces amygdala
      differentiation pointing to a lowered learning ability of the defense system
      under high cortisol concentrations, irrespective of current sex hormone
      availability.

PMID- 22986338
TI  - Juvenile hormone levels reflect social opportunities in the facultatively
      eusocial sweat bee Megalopta genalis (Hymenoptera: Halictidae).
AB  - The evolution of eusociality is hypothesized to have involved de-coupling
      parental care from reproduction mediated by changes in endocrine regulation.
      While data for obligately eusocial insects are consistent with this hypothesis,
      we lack information from species representative of the transition from solitary
      reproduction to eusociality. Here we report the first evidence for a link between
      endocrine processes and social behavior in a facultatively eusocial bee,
      Megalopta genalis (Halictidae). Using females that varied in social,
      reproductive, and ecological context, we measured juvenile hormone (JH), a major
      regulator of colony caste dynamics in other eusocial species. JH was low at adult
      emergence, but elevated after 10 days in all nesting females. Females reared in
      cages with ad lib nutrition, however, did not elevate JH levels after 10 days.
      All reproductive females had significantly more JH than all age-matched non
      reproductive females, suggesting a gonadotropic function. Among females in
      established nests, JH was higher in queens than workers and solitary
      reproductives, suggesting a role for JH in social dominance. A lack of
      significant differences in JH between solitary reproductives and non-reproductive
      workers suggests that JH content reflects more than reproductive status. Our data
      support the hypothesis that endocrine modifications are involved in the
      evolutionary decoupling of reproductive and somatic effort in social insects.
      These are the first measurements of JH in a solitary-nesting hymenopteran, and
      the first to compare eusocial and solitary nesting individuals of the same
      species.

PMID- 22986337
TI  - Peripheral oxytocin in female baboons relates to estrous state and maintenance of
      sexual consortships.
AB  - The neuro-hypophysial hormone oxytocin (OT) has been implicated in female
      reproductive and maternal behaviors and in the formation of pair bonds in
      monogamous species. Here we measure variation in urinary OT concentrations in
      relation to reproductive biology and socio-sexual behavior in a promiscuously
      breeding species, the chacma baboon (Papio hamadryas ursinus). Subjects were
      members of a habituated group of baboons in the Okavango Delta, Botswana. We
      collected behavioral data and urine samples from n=13 cycling females across
      their estrous cycles and during and outside short-term, exclusive sexual
      consortships. Samples were analyzed via enzyme immunoassay (EIA) and we used
      linear mixed models (LMM) to explore the relationship between peripheral OT and a
      female's estrous stage and consortship status, her previous reproductive
      experience and fertility. We also used a Pearson's correlation to examine the
      relationship between OT concentrations of consorting females and their extent of
      behavioral coordination with their consort partners. The results of the LMM
      indicate that only estrous stage had a significant influence on OT levels.
      Females had higher OT levels during their periovulatory period than during other
      stages of their estrous cycle. There were no differences in the OT levels between
      consorting and non-consorting periovulatory females. However, among consorting
      females, there was a significant positive relationship between urinary OT levels
      and the maintenance of close proximity between consort partners. Our results
      suggest that physiological and behavioral changes associated with the initiation
      and maintenance of short-term inter-sexual relationships in baboons correspond
      with changes in peripheral OT.

PMID- 22986339
TI  - Clinical characteristics and outcomes of patients with clinically unsuspected
      pulmonary embolism versus patients with clinically suspected pulmonary embolism.
AB  - BACKGROUND: The routine use of multidetector computed tomography has led to
      increased detection of unsuspected pulmonary embolism (UPE), with questionable
      benefit for diagnosis and treatment. OBJECTIVE: The purpose of this work was to
      compare the clinical characteristics and prognosis of patients with UPE to
      patients with suspected PE (SPE). METHODS: We retrospectively reviewed the charts
      of patients diagnosed with PE in a community-based university hospital between
      the years 2002 and 2007. UPE was defined as PE detected on CT scans performed for
      indications other than suspicion of PE. We compared patients with UPE to patients
      with SPE for differences in clinical features, electrocardiogram, imaging and
      echocardiographic findings. We also assessed the long-term outcomes using
      electronic patient records. RESULTS: Of 500 patients with PE, 408 had SPE and 92
      had UPE. Patients with UPE were similar to patients with SPE regarding age and
      sex distribution. Malignancy was more prevalent in UPE patients (39 vs. 23%, p <
      0.0068). UPE patients had significantly less tachypnea (37 vs. 57%, p = 0.0005),
      dyspnea (47 vs. 87%, p < 0.0001), chest pain (19 vs. 42%, p < 0.0001) and
      hypoxemia (36 vs. 55%, p = 0.0011). Mortality was higher in UPE patients (70.3
      vs. 53%, p = 0.0029). The hazard ratio after adjustment for confounders including
      age, sex and malignancy was 1.546 (95% CI: 1.139-2.099, p = 0.0052). CONCLUSIONS:
      We suggest that UPE is more prevalent in patients with a malignancy and is
      associated with higher mortality despite a less severe clinical presentation. UPE
      may be a marker of poor prognosis.

PMID- 22986341
TI  - Characterization of a Wnt-binding site of the WIF-domain of Wnt inhibitory factor
      1.
AB  - A Wnt-binding site of the WIF-domain of Wnt inhibitory factor-1 was localized by
      structure-guided arginine-scanning mutagenesis in combination with surface
      plasmon resonance assays. Our observation that substitution of some residues of
      WIF resulted in an increased affinity for Wnt5a, but decreased affinity for
      Wnt3a, suggests that these residues may define the specificity spectrum of WIF
      for Wnts. These results hold promise for a more specific targeting of Wnt family
      members with WIF variants in various forms of cancer.

PMID- 22986340
TI  - Congenital anomalies: treatment options based on amniotic fluid-derived stem
      cells.
AB  - Over the past decade, amniotic fluid-derived stem cells have emerged as a novel,
      experimental approach for the treatment of a wide variety of congenital anomalies
      diagnosed either in utero or postnatally. There are a number of unique properties
      of amniotic fluid stem cells that have allowed it to become a major research
      focus. These include the relative ease of accessing amniotic fluid cells in a
      minimally invasive fashion by amniocentesis as well as the relatively rich
      population of progenitor cells obtained from a small aliquot of fluid.
      Mesenchymal stem cells, c-kit positive stem cells, as well as induced pluripotent
      stem cells have all been derived from human amniotic fluid in recent years. This
      article gives a pediatric surgeon's perspective on amniotic fluid stem cell
      therapy for the management of congenital anomalies. The current status in the use
      of amniotic fluid-derived stem cells, particularly as they relate as substrates
      in tissue engineering-based applications, is described in various animal models.
      A roadmap for further study and eventual clinical application is also proposed.

PMID- 22986342
TI  - Coilin levels modulate cell cycle progression and gammaH2AX levels in etoposide
      treated U2OS cells.
AB  - Coilin is considered the Cajal body (CB) marker protein. In this report, we
      investigated the role of coilin in the DNA damage response and found that coilin
      reduction correlated with significantly increased levels of soluble gammaH2AX in
      etoposide treated U2OS cells. Additionally, coilin levels influenced the
      proliferation rate and cell cycle distribution of cells exposed to etoposide.
      Moreover, coilin overexpression inhibited nucleolar localization of endogenous
      coilin in etoposide treated U2OS cells. Collectively, these data provide
      additional evidence for coilin and CBs in the DNA damage response.

PMID- 22986343
TI  - Characterization of the direct physical interaction of nc886, a cellular non
      coding RNA, and PKR.
AB  - We have recently shown that nc886 (pre-miR-886 or vtRNA2-1) is not a genuine
      microRNA precursor nor a vault RNA, but a novel type of non-coding RNA that
      represses PKR, a double-stranded RNA (dsRNA) dependent kinase. Here we have
      characterized their direct physical association. PKR's two RNA binding domains
      form a specific and stable complex with nc886's central portion, without any
      preference to its 5'-end structure. By binding to PKR with a comparable affinity,
      nc886 competes with dsRNA and attenuates PKR activation by dsRNA. Our data
      suggest that nc886 sets a threshold for PKR activation so that it occurs only
      during genuine viral infection but not by a minute level of fortuitous cellular
      dsRNA.

PMID- 22986345
TI  - The molecular genetics of ovarian differentiation in the avian model.
AB  - In birds as in mammals, sex is determined at fertilization by the inheritance of
      sex chromosomes. However, sexual differentiation - development of a male or
      female phenotype - occurs during embryonic development. Sex differentiation
      requires the induction of sex-specific developmental pathways in the gonads,
      resulting in the formation of ovaries or testes. Birds utilize a different sex
      chromosome system to that of mammals, where females are the heterogametic sex
      (carrying Z and W chromosomes), while males are homogametic (carrying 2 Z
      chromosomes). Therefore, while some genes essential for testis and ovarian
      development are conserved, important differences also exist. Namely, the key
      mammalian male-determining factor SRY does not exist in birds, and another
      transcription factor, DMRT1, plays a central role in testis development. In
      contrast to our understanding of testis development, ovarian differentiation is
      less well-characterized. Given the presence of a female-specific chromosome,
      studies in chicken will provide insight into the induction and function of female
      specific gonadal pathways. In this review, we discuss sexual differentiation in
      chicken embryos, with emphasis on ovarian development. We highlight genes that
      may play a conserved role in this process, and discuss how interaction between
      ovarian pathways may be regulated.

PMID- 22986346
TI  - Hyperpolarized xenon for NMR and MRI applications.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) suffer from
      intrinsic low sensitivity because even strong external magnetic fields of ~10 T
      generate only a small detectable net-magnetization of the sample at room
      temperature (1). Hence, most NMR and MRI applications rely on the detection of
      molecules at relative high concentration (e.g., water for imaging of biological
      tissue) or require excessive acquisition times. This limits our ability to
      exploit the very useful molecular specificity of NMR signals for many biochemical
      and medical applications. However, novel approaches have emerged in the past few
      years: Manipulation of the detected spin species prior to detection inside the
      NMR/MRI magnet can dramatically increase the magnetization and therefore allows
      detection of molecules at much lower concentration (2). Here, we present a method
      for polarization of a xenon gas mixture (2-5% Xe, 10% N2, He balance) in a
      compact setup with a ca. 16000-fold signal enhancement. Modern line-narrowed
      diode lasers allow efficient polarization (7) and immediate use of gas mixture
      even if the noble gas is not separated from the other components. The SEOP
      apparatus is explained and determination of the achieved spin polarization is
      demonstrated for performance control of the method. The hyperpolarized gas can be
      used for void space imaging, including gas flow imaging or diffusion studies at
      the interfaces with other materials (8,9). Moreover, the Xe NMR signal is
      extremely sensitive to its molecular environment (6). This enables the option to
      use it as an NMR/MRI contrast agent when dissolved in aqueous solution with
      functionalized molecular hosts that temporarily trap the gas (10,11). Direct
      detection and high-sensitivity indirect detection of such constructs is
      demonstrated in both spectroscopic and imaging mode.

PMID- 22986347
TI  - Statin upregulates the expression of klotho, an anti-aging gene, in experimental
      cyclosporine nephropathy.
AB  - BACKGROUND: We recently reported that long-term cyclosporine (CsA)-induced
      oxidative stress is associated with decreased expression of klotho, an anti-aging
      gene. This study evaluated whether the antioxidant effect of statin might
      upregulate klotho expression in CsA-induced renal injury. METHODS: Two separate
      experiments were performed. First, the dose-dependent effect of statin on klotho
      expression was evaluated in normal mouse kidneys. Second, the effect of statin on
      klotho expression was evaluated in experimental chronic CsA nephropathy in mice.
      We performed immunohistochemistry and immunoblotting for klotho, Forkhead box O
      transcription factors [FoxOs; phosphorylated FoxO1 (p-FoxO1) and FoxO3a (p
      FoxO3a)] and their target molecules, manganese superoxide dismutase (MnSOD), Bim
      and hemeoxygenase-1. RESULTS: Statin treatment upregulated klotho expression in a
      dose-dependent manner in the normal mouse kidney and alleviated the decrease in
      klotho expression in kidneys exhibiting CsA nephropathy. CsA administration
      increased p-FoxO1 expression and decreased p-FoxO3a expression, whereas
      concurrent statin treatment reversed these changes, increased the expression of
      the antioxidant enzymes MnSOD and hemeoxygenase-1 and decreased the expression of
      the pro-apoptotic protein Bim. CONCLUSION: Statin-mediated upregulation of klotho
      expression and differential regulation of FoxO expression promote resistance to
      CsA-induced oxidative stress.

PMID- 22986348
TI  - Reengineered epipodophyllotoxin.
AB  - A variant structural skeleton of epipodophyllotoxin was synthesized and found to
      rival the natural cyclolignan in antiproliferative and microtubule destabilizing
      properties. This discovery leads to a new structural class of tubulin targeting
      agents.

PMID- 22986350
TI  - Solvent-induced supramolecular isomers, structural diversity, and unprecedented
      in situ formation of both inorganic and organic ions in inorganic-organic
      mercury(II) complexes.
AB  - Reported here is, for the first time, an important study of solvent effect on
      structural diversity in inorganic-organic mercury(II) complexes. As a result, the
      first supramolecular isomer in mercury(II) complexes is obtained. Importantly, a
      previously unobserved in situ generation of both inorganic (Cl(-)) and organic
      ([CH(3)-L1-CH(3)](2+)) ions was also observed.

PMID- 22986349
TI  - Early and delayed tranilast treatment reduces pathological fibrosis following
      myocardial infarction.
AB  - BACKGROUND: Tranilast has been shown to inhibit TGFbeta1-related fibrosis and
      organ failure in various disease models. We sought to examine the effects of
      tranilast on left ventricular (LV) remodelling post-MI. METHODS: Following
      coronary artery ligation, Sprague Dawley rats were randomised to receive
      tranilast (300mg/kg/d, p.o.) or vehicle control over one of two treatment
      periods: (1) from 24h until seven days post-MI, (2) from seven days to 28 days
      post-MI. Cardiac tissue was harvested for molecular, immunohistochemical and cell
      culture analyses. RESULTS: Tranilast treatment of MI rats from 24h until seven
      days post-MI reduced myocardial collagen content, alpha1 (I) procollagen,
      TGFbeta1 and CTGF mRNA transcripts, monocyte/macrophage infiltration and
      exacerbated infarct expansion compared with vehicle-treatment. Delaying the
      commencement of tranilast treatment to seven days post-MI attenuated myocardial
      fibrosis, gene expression of alpha1(I) procollagen, alpha1(III) procollagen,
      fibronectin, TGFbeta1 and CTGF mRNA transcripts, and monocyte/macrophage
      infiltration at 28d compared to vehicle-treatment, without detriment to infarct
      healing. Extended post-MI also preserved LV infarct size. In cultures of rat
      cardiac fibroblasts, tranilast attenuated TGFbeta1-stimulated fibrogenesis.
      CONCLUSION: Tranilast inhibits myocardial TGFbeta1 expression, fibrosis in rat
      post-MI and collagen production in cardiac fibroblasts. While tranilast
      intervention from 24h post-MI exacerbated infarct expansion, delaying the
      commencement of treatment to seven days post-MI impeded LV remodelling.

PMID- 22986351
TI  - Differentiating hepatocellular carcinoma from dysplastic nodules at gadobenate
      dimeglumine-enhanced hepatobiliary-phase magnetic resonance imaging.
AB  - PURPOSE: We evaluated whether the addition of delayed phase imaging (DPI)
      gadobenate dimeglumine-enhanced MRI to dynamic postcontrast imaging improves the
      characterization of small hepatocellular carcinoma (HCC) and the differentiation
      between HCC, high grade dysplastic nodules (HGDN), and low grade dysplastic
      nodules (LGDN). METHODS: Twenty-five cirrhotic patients with 30 nodules (16 HCC,
      8 HGDNs, and 6 LGDNs; maximum size of 3 cm) were included in this retrospective
      study. The diagnostic reference standard was histology. All the patients
      underwent MRI both prior to and following intravenous administration of
      gadobenate dimeglumine. The lesions were classified as hypointense, isointense,
      hyperintense on DPI for qualitative assessment. In the quantitative analysis the
      relative tumor-liver contrast to noise ratio (CNR) of the lesions on DPI was
      calculated. RESULTS: All HCCs were hypointense on DPI while only 8 (57.1%) of 14
      DNs were hypointense and only 1 of 6 (16.6%) LGDNs was hypointense. There was a
      statistically significant difference in the hypointensity on DPI between HCCs and
      DNs (p = 0.003) in the qualitative analysis but not in the CNR values while there
      was a strong statistically significant difference in the hypointensity on DPI in
      the qualitative (p = 0.00001) and quantitative analysis (p < 0.05) between LGDNs
      and the group obtained by unifying HGDNs and HCCs. CONCLUSION: DPI is helpful in
      differentiating HCCs and HGDNs from LGDNs. Demonstration of hypointensity on DPI
      should raise the suspicion of HGDN or hypovascular HCC in the case of nodules
      with atypical dynamic pattern.

PMID- 22986352
TI  - Defining vascular signatures of benign hepatic masses: role of MDCT with 3D
      rendering.
AB  - Multidetector CT (MDCT) provides new opportunities for hepatic tumor
      characterization. By coupling high-resolution isotropic datasets with advanced
      post-processing tools, maps of tumor vascularity can be generated to elucidate
      characteristic findings. This two-part review describes a range of benign and
      malignant liver masses, with emphasis on IV contrast-enhanced MDCT features and
      vascular signatures that can be identified on 3D vascular mapping.

PMID- 22986353
TI  - Gadofosveset-enhanced MRI for the assessment of rectal cancer lymph nodes:
      predictive criteria.
AB  - PURPOSE: To confirm the use of the nodal signal intensity (SI) and the 'chemical
      shift' artefact as diagnostic criteria for detecting nodal metastases from rectal
      cancer on gadofosveset contrast-enhanced MRI. METHODS: Thirty-three patients
      underwent a non-enhanced and gadofosveset-enhanced 3D-T1W GRE-MRI at 1.5T. For
      each lymph node, the SI of the middle part of the node (mSI) and white rim of the
      chemical shift artefact encircling the node (wSI) were measured on the non
      enhanced and gadofosveset-enhanced images. Second, the aspect of the chemical
      shift artefact encircling the nodes was scored using a 4-point scale. Results
      were compared with histology on a node-by-node basis. RESULTS: 289 nodes (55 N+)
      were analysed. On gadofosveset-MRI, mSI and wSI were significantly higher for the
      benign than for the metastatic lymph nodes (p < 0.001). Areas under the ROC curve
      (AUC) for identification of metastases were 0.74 (mSI) and 0.73 (wSI). The
      chemical shift criterion rendered an AUC of 0.85. The combination of mSI and the
      chemical shift criterion resulted in an AUC of 0.88 and the rendered an AUC of
      0.86-0.92 when subjectively (visually) assessed by two independent readers.
      CONCLUSIONS: Benign lymph nodes show significant contrast enhancement after
      gadofosveset injection, while metastatic nodes do not. The uptake of gadofosveset
      in the nodes also affects the chemical shift artefact encircling the nodes.
      Combined assessment of these two features on gadofosveset-enhanced MRI provides a
      high diagnostic performance for diagnosing metastatic lymph nodes in patients
      with rectal cancer.

PMID- 22986354
TI  - Adult-onset opsoclonus-myoclonus syndrome.
AB  - BACKGROUND Little is known about adult-onset opsoclonus-myoclonus syndrome (OMS)
      outside of individual case reports. OBJECTIVE To describe adult-onset OMS. DESIGN
      Review of medical records (January 1, 1990, through December 31, 2011),
      prospective telephone surveillance, and literature review (January 1, 1967,
      through December 31, 2011). SETTING Department of Neurology, Mayo Clinic,
      Rochester, Minnesota. PATIENTS Twenty-one Mayo Clinic patients and 116 previously
      reported patients with adult-onset OMS. MAIN OUTCOME MEASURES Clinical course and
      longitudinal outcomes. RESULTS The median age at onset of the 21 OMS patients at
      the Mayo Clinic was 47 years (range, 27-78 years); 11 were women. Symptoms
      reported at the first visit included dizziness, 14 patients; balance
      difficulties, 14; nausea and/or vomiting, 10; vision abnormalities, 6;
      tremor/tremulousness, 4; and altered speech, 2. Myoclonus distribution was
      extremities, 15 patients; craniocervical, 8; and trunk, 4. Cancer was detected in
      3 patients (breast adenocarcinoma, 2; and small cell lung carcinoma, 1); a
      parainfectious cause was assumed in the remainder of the patients. Follow-up of 1
      month or more was available for 19 patients (median, 43 months; range, 1-187
      months). Treatment (median, 6 weeks) consisted of immunotherapy and symptomatic
      therapy in 16 patients, immunotherapy alone for 2, and clonazepam alone for 1. Of
      these 19 patients, OMS remitted in 13 and improved in 3; 3 patients died
      (neurologic decline, 1; cancer, 1; and myocardial infarction, 1). The cause of
      death was of paraneoplastic origin in 60 of 116 literature review patients, with
      the most common carcinomas being lung (33 patients) and breast (7); the most
      common antibody was antineuronal nuclear antibody type 2 (anti-Ri, 15). Other
      causes were idiopathic in origin, 38 patients; parainfectious, 15 (human
      immunodeficiency virus, 7); toxic/metabolic, 2; and other autoimmune, 1. Both
      patients with N -methyl-D-aspartate receptor antibody had encephalopathy.
      Improvements were attributed to immunotherapy alone in 22 of 28 treated patients.
      CONCLUSIONS Adult-onset OMS is rare. Paraneoplastic and parainfectious causes
      (particularly human immunodeficiency virus) should be considered. Complete
      remission achieved with immunotherapy is the most common outcome.

PMID- 22986356
TI  - Contribution of large scale biases in decoding of direction-of-motion from high
      resolution fMRI data in human early visual cortex.
AB  - Previous studies have demonstrated that the perceived direction of motion of a
      visual stimulus can be decoded from the pattern of functional magnetic resonance
      imaging (fMRI) responses in occipital cortex using multivariate analysis methods
      (Kamitani and Tong, 2006). One possible mechanism for this is a difference in the
      sampling of direction selective cortical columns between voxels, implying that
      information at a level smaller than the voxel size might be accessible with fMRI.
      Alternatively, multivariate analysis methods might be driven by the organization
      of neurons into clusters or even orderly maps at a much larger scale. To assess
      the possible sources of the direction selectivity observed in fMRI data, we
      tested how classification accuracy varied across different visual areas and
      subsets of voxels for classification of motion-direction. To enable high spatial
      resolution functional MRI measurements (1.5mm isotropic voxels), data were
      collected at 7T. To test whether information about the direction of motion is
      represented at the scale of retinotopic maps, we looked at classification
      performance after combining data across different voxels within visual areas (V1
      3 and MT+/V5) before training the multivariate classifier. A recent study has
      shown that orientation biases in V1 are both necessary and sufficient to explain
      classification of stimulus orientation (Freeman et al., 2011). Here, we combined
      voxels with similar visual field preference as determined in separate retinotopy
      measurements and observed that classification accuracy was preserved when
      averaging in this 'retinotopically restricted' way, compared to random averaging
      of voxels. This insensitivity to averaging of voxels (with similar visual angle
      preference) across substantial distances in cortical space suggests that there
      are large-scale biases at the level of retinotopic maps underlying our ability to
      classify direction of motion.

PMID- 22986355
TI  - Finding thalamic BOLD correlates to posterior alpha EEG.
AB  - Oscillatory electrical brain activity in the alpha (8-13 Hz) band is a prominent
      feature of human electroencephalography (EEG) during alert wakefulness, and is
      commonly thought to arise primarily from the occipital and parietal parts of the
      cortex. While the thalamus is considered to play a supportive role in the
      generation and modulation of cortical alpha rhythms, its precise function remains
      controversial and incompletely understood. To address this, we evaluated the
      correlation between the blood oxygenation level dependent (BOLD) functional
      magnetic resonance imaging (fMRI) signals in the thalamus and the spontaneous
      modulation of posterior alpha rhythms based on EEG-fMRI data acquired
      concurrently during an eyes-closed task-free condition. We observed both negative
      and positive correlations in the thalamus. The negative correlations were mostly
      seen within the visual thalamus, with a preference for the pulvinar over lateral
      geniculate nuclei. The positive correlations were found at the anterior and
      medial dorsal nuclei. Through functional connectivity analysis of the fMRI data,
      the pulvinar was found to be functionally associated with the same widespread
      cortical visual areas where the fMRI signals were negatively correlated with the
      posterior alpha modulation. In contrast, the dorsal nuclei were part of a
      distinct functional network that included brain stem, cingulate cortex and
      cerebellum. These observations are consistent with previous animal
      electrophysiology studies and the notion that the visual thalamus, and the
      pulvinar in particular, is intimately involved in the generation and spontaneous
      modulation of posterior alpha rhythms, facilitated by its reciprocal and
      widespread interaction with the cortical visual areas. We further postulate that
      the anterior and medial dorsal nuclei, being part of the ascending
      neuromodulatory system, may indirectly modulate cortical alpha rhythms by
      affecting vigilance and arousal levels.

PMID- 22986357
TI  - Absolute quantification of resting oxygen metabolism and metabolic reactivity
      during functional activation using QUO2 MRI.
AB  - We have recently described an extension of calibrated MRI, which we term QUO2
      (for QUantitative O(2) imaging), providing absolute quantification of resting
      oxidative metabolism (CMRO(2)) and oxygen extraction fraction (OEF(0)). By
      combining BOLD, arterial spin labeling (ASL) and end-tidal O(2) measurements in
      response to hypercapnia, hyperoxia and combined hyperoxia/hypercapnia
      manipulations, and the same MRI measurements during a task, a comprehensive set
      of vascular and metabolic measurements can be obtained using a generalized
      calibration model (GCM). These include the baseline absolute CBF in units of
      ml/100g/min, cerebrovascular reactivity (CVR) in units of %Delta CBF/mm Hg, M in
      units of percent, OEF(0) and CMRO(2) at rest in units of MUmol/100g/min, percent
      evoked CMRO(2) during the task and n, the value for flow-metabolic coupling
      associated with the task. The M parameter is a calibration constant corresponding
      to the maximal BOLD signal that would occur upon removal of all deoxyhemoglobin.
      We have previously shown that the GCM provides estimates of the above resting
      parameters in grey matter that are in excellent agreement with literature. Here
      we demonstrate the method using functionally-defined regions-of-interest in the
      context of an activation study. We applied the method under high and low signal
      to-noise conditions, corresponding respectively to a robust visual stimulus and a
      modified Stroop task. The estimates fall within the physiological range of
      literature values, showing the general validity of the GCM approach to yield non
      invasively an extensive array of relevant vascular and metabolic parameters.

PMID- 22986358
TI  - Altered resting-state functional connectivity after cortical spreading depression
      in mice.
AB  - Cortical spreading depression (CSD) underlies some neurological disorders.
      Previous imaging work suggests that CSD is associated with functional and
      structural alterations in the cerebral cortex. However, the changes in cortical
      functional network following CSD are poorly understood. The present study
      examines the changes in resting-state function connectivity (RSFC) of the mouse
      sensorimotor cortex after the onset of CSD by using optical intrinsic signal
      imaging. Our results show that RSFC between ipsilateral sensorimotor cortex (the
      cortex where CSD spreads) and contralateral sensorimotor cortex (the cortex where
      CSD does not spread) was significantly reduced after CSD. Moreover, a marked
      connectivity increase was found after CSD not only within contralateral
      somatosensory cortex and contralateral motor cortex themselves, but also between
      contralateral somatosensory cortex and contralateral motor cortex. Amplitude of
      low-frequency fluctuation (ALFF) analysis revealed an increase in ALFF in the
      ipsilateral cortex but a decrease in the contralateral cortex after CSD,
      indicating different effects of CSD on the neural activity in the ipsilateral and
      contralateral sensorimotor cortexes. These results suggest that CSD would alter
      the RSFC in the sensorimotor cortexes, and functional connectivity analysis may
      help to understand the effect of CSD on the cerebral functional network.

PMID- 22986359
TI  - Chronic kidney disease: Reduced kidney function and abnormal cardiac structure.

PMID- 22986361
TI  - Transplantation: Pre-emptive CMV therapy versus universal CMV prophylaxis in
      renal transplant recipients.

PMID- 22986360
TI  - STEC-HUS, atypical HUS and TTP are all diseases of complement activation.
AB  - Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP)
      are diseases characterized by microvascular thrombosis, with consequent
      thrombocytopaenia, haemolytic anaemia and dysfunction of affected organs.
      Advances in our understanding of the molecular pathology led to the recognition
      of three different diseases: typical HUS caused by Shiga toxin-producing
      Escherichia coli (STEC-HUS); atypical HUS (aHUS), associated with genetic or
      acquired disorders of regulatory components of the complement system; and TTP
      that results from a deficiency of ADAMTS13, a plasma metalloprotease that cleaves
      von Willebrand factor. In this Review, we discuss data indicating that complement
      hyperactivation is a common pathogenetic effector that leads to endothelial
      damage and microvascular thrombosis in all three diseases. In STEC-HUS, the toxin
      triggers endothelial complement deposition through the upregulation of P-selectin
      and possibly interferes with the activity of complement regulatory molecules. In
      aHUS, mutations in the genes coding for complement components predispose to
      hyperactivation of the alternative pathway of complement. In TTP, severe ADAMTS13
      deficiency leads to generation of massive platelet thrombi, which might
      contribute to complement activation. More importantly, evidence is emerging that
      pharmacological targeting of complement with the anti-C5 monoclonal antibody
      eculizumab can effectively treat not only aHUS for which it is indicated, but
      also STEC-HUS and TTP in some circumstances.

PMID- 22986363
TI  - Pramipexole upregulates dopamine receptor D2 and D3 expression in rat striatum.
AB  - Randomized clinical trials have shown that pramipexole has an antidepressant
      effect in patients with Parkinson's disease. We investigated the comparative
      efficacy of pramipexole toward dopamine receptor D(2) and D(3) expression in rat
      brain. Groups of rats were treated subacutely with pramipexole (1 mg/kg),
      imipramine (10 mg/kg), or bromocriptine (5 mg/kg), with appropriate controls.
      Using real-time RT-PCR and immunoblotting, dopamine receptor D(2) and D(3)
      expression was up-regulated in the striatum following pramipexole treatment,
      while imipramine and bromocriptine had no significant effects. These findings
      support that pramipexole exerts additional therapeutic benefits such as
      decreasing depression by increasing dopamine receptor D(3) expression in the
      striatum.

PMID- 22986362
TI  - Renal and neurological involvement in typical Shiga toxin-associated HUS.
AB  - Shiga toxin-producing Escherichia coli-associated haemolytic uraemic syndrome
      (STEC-HUS) is one of the most important causes of acute kidney injury in patients
      of all ages, especially in children. It can occur sporadically or in outbreaks.
      STEC-HUS is a systemic illness caused by toxin-mediated injury to the vascular
      endothelium and a generalized inflammatory response. The kidney and the brain are
      the two primary target organs. Nearly 40% of patients with STEC-HUS require at
      least temporary renal replacement therapy and up to 20% will have permanent
      residual kidney dysfunction. Neurological injury can be sudden and severe and is
      the most frequent cause of acute mortality in patients with STEC-HUS. Over the
      past 30 years, a wide range of inflammatory mediators have been linked to the
      pathogenesis of STEC-HUS and associated renal and neurological complications.
      Recently, evidence has accumulated that abnormal activation of the alternative
      pathway of complement occurs in patients with STEC-HUS. In the large outbreak of
      STEC-HUS caused by E. coli O104:H4 that occurred in Germany in May 2011, a large
      number of patients received eculizumab, a monoclonal antibody directed against
      C5, in an open-label manner. We describe the experience with eculizumab under
      these emergent circumstances at one large centre.

PMID- 22986364
TI  - Evaluation of formalin-induced pain behavior and glutamate release in the spinal
      dorsal horn using in vivo microdialysis in conscious rats.
AB  - Measurement of neurotransmitters in the spinal dorsal horn in conscious animals
      remains a technical challenge. Here we applied concentric microdialysis to
      measure formalin-induced glutamate (Glu) release in the ipsilateral dorsal horn
      in conscious, freely-moving rats. Hind paw formalin injection induced flinching
      nociceptive behaviors accompanied by increased Glu in the dorsal horn (maximum =
      294%). Both flinching and Glu increase were prevented by morphine (3 mg/kg,
      s.c.). Accordingly, concentric microdialysis is a sensitive technique for
      studying neurochemical modulation induced by pain and analgesics in the spinal
      dorsal horn of awake rats. Measurement of Glu provides information on modulation
      of excitatory signals.

PMID- 22986365
TI  - Discriminative stimulus effects of hallucinogenic drugs: a possible relation to
      reinforcing and aversive effects.
AB  - The subjective effects of drugs are related to the kinds of feelings they
      produce, such as euphoria or dysphoria. One of the methods that can be used to
      study these effects is the drug discrimination procedure. Many researchers are
      trying to elucidate the mechanisms that underlie the discriminative stimulus
      effects of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the
      past two decades, the patterns of drug abuse have changed, so that
      club/recreational drugs such as phencyclidine (PCP), 3,4
      methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and
      ketamine, which induce perceptual distortions, like hallucinations, are now more
      commonly abused, especially in younger generations. However, the mechanisms of
      the discriminative stimulus effects of hallucinogenic drugs are not yet fully
      clear. This review will briefly focus on the recent findings regarding
      hallucinogenic/psychotomimetic drug-induced discriminative stimulus effects in
      animals. In summary, recent research has demonstrated that there are at least two
      plausible mechanisms that can explain the cue of the discriminative stimulus
      effects of hallucinogenic drugs; one is mediated mainly by 5-HT(2) receptors, and
      the other is mediated through sigma-1 (sigma(1))-receptor chaperone regulated by
      endogenous hallucinogenic ligand.

PMID- 22986366
TI  - Roles of dopamine and inflammation-related molecules in behavioral alterations
      caused by repeated stress.
AB  - Prolonged or intensive stress results in emotional and cognitive deficits and is
      a major risk factor for psychiatric disorders such as depression. Since the
      molecular mechanisms of how biological adaptations to stress go awry remains
      elusive, pharmaceutical development targeting stress has not been established. In
      rodents, repeated stress alters functions of multiple brain areas including the
      medial prefrontal cortex (mPFC) that confers stress resilience, thereby causing
      depression, anxiety, and working memory deficit. The mesocortical dopaminergic
      pathway that regulates such stress-coping functions is attenuated with repetition
      of stress via prostaglandin (PG) E(2), a bioactive lipid derived from arachidonic
      acid, and its receptor EP1. Several findings suggest that microglia activated by
      repeated stress are involved in emotional and cognitive changes as a source of
      inflammation-related molecules such as PGE(2) and IL-1beta. IL-1 signaling is
      critical not only for emotional changes but also for microglial activation
      induced by repeated stress. Furthermore, purinergic signaling via the P2X7
      receptor that can trigger PGE(2) and IL-1beta production in microglia has been
      implicated in the pro-depressive effect of repeated stress as well as depressive
      disorders. Collectively, inflammation-related molecules that link repeated stress
      to mPFC dysfunction are potential targets of pharmaceutical development for
      psychiatric disorders.

PMID- 22986367
TI  - Dilated cardiomyopathy and mitochondrial dysfunction in Sirt1-deficient mice: a
      role for Sirt1-Mef2 in adult heart.
AB  - The deacetylase Sirtuin-1 (Sirt1) is involved in the cardiac hypertrophic
      responses and cardiac embryo morphogenesis. However, the physiological function
      of Sirt1 deficiency in the postnatal development of the heart remains to be
      characterized. The aim of the study was to investigate the relevance of Sirt1 in
      the development and function of the myocardium. Hearts from Sirt1-deficient mice
      partially or totally lacking Sirt1 protein activity were analyzed. Loss of Sirt1
      activity led to dilated cardiomyopathy in adult hearts, a phenotype accompanied
      by reduced cardiomyocyte size and the absence of fibrosis. Morphological and
      functional mitochondrial abnormalities were observed in the adult hearts lacking
      Sirt1, suggesting that mitochondrial dysfunction contributes to the progression
      of the observed cardiomyopathy. Moreover, gene expression analyses revealed that
      mitochondrial genes were the most affected in Sirt1-deficient mice, showing a
      reduction in their expression. No overt cardiac dilatation was observed in
      neonates lacking Sirt1 activity, but first signs of mitochondrial alterations
      were already present. Immunoblot analyses revealed that Sirt1 is highly expressed
      in the heart after birth, indicating the importance of Sirt1 in the neonatal
      period. Finally, Sirt1 deficiency affected the acetylation pattern of the myocyte
      enhancer factor 2 (Mef2) transcription factors, which are critical for normal
      heart development and mitochondrial integrity. Collectively, our findings
      indicate that Sirt1 is essential for the maintenance of cardiac mitochondrial
      integrity and normal postnatal myocardium development.

PMID- 22986368
TI  - Whole blood transcriptome correlates with treatment response in nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Treatment protocols for nasopharyngeal carcinoma (NPC) developed in
      the past decade have significantly improved patient survival. In most NPC
      patients, however, the disease is diagnosed at late stages, and for some patients
      treatment response is less than optimal. This investigation has two aims: to
      identify a blood-based gene-expression signature that differentiates NPC from
      other medical conditions and from controls and to identify a biomarker signature
      that correlates with NPC treatment response. METHODS: RNA was isolated from
      peripheral whole blood samples (2 x 10 ml) collected from NPC patients/controls
      (EDTA vacutainer). Gene expression patterns from 99 samples (66 NPC; 33 controls)
      were assessed using the Affymetrix array. We also collected expression data from
      447 patients with other cancers (201 patients) and non-cancer conditions (246
      patients). Multivariate logistic regression analysis was used to obtain biomarker
      signatures differentiating NPC samples from controls and other diseases.
      Differences were also analysed within a subset (n=28) of a pre-intervention case
      cohort of patients whom we followed post-treatment. RESULTS: A blood-based gene
      expression signature composed of three genes - LDLRAP1, PHF20, and LUC7L3 - is
      able to differentiate NPC from various other diseases and from unaffected
      controls with significant accuracy (area under the receiver operating
      characteristic curve of over 0.90). By subdividing our NPC cohort according to
      the degree of patient response to treatment we have been able to identify a blood
      gene signature that may be able to guide the selection of treatment. CONCLUSION:
      We have identified a blood-based gene signature that accurately distinguished NPC
      patients from controls and from patients with other diseases. The genes in the
      signature, LDLRAP1, PHF20, and LUC7L3, are known to be involved in carcinoma of
      the head and neck, tumour-associated antigens, and/or cellular signalling. We
      have also identified blood-based biomarkers that are (potentially) able to
      predict those patients who are more likely to respond to treatment for NPC. These
      findings have significant clinical implications for optimizing NPC therapy.

PMID- 22986369
TI  - Primordial germ cells (spermatogonial stem cells) of bullfrogs express sex
      hormone-binding globulin and steroid receptors during seasonal spermatogenesis.
AB  - In vertebrate species, testosterone seems to inhibit spermatogonial
      differentiation and proliferation. However, this androgen can also be converted,
      via aromatase, into estrogen which stimulates spermatogonial differentiation and
      mitotic activity. During seasonal spermatogenesis of adult bullfrogs Lithobates
      catesbeianus, primordial germ cells (PGCs) show enhanced testosterone cytoplasm
      immunoexpression in winter; however, in summer, weak or no testosterone
      immunolabelling was observed. The aim of this study was to confirm if PGCs
      express stem cell markers - alkaline phosphatase (AP) activity and GFRalpha1
      (glial-cell-line-derived neurotrophic factor) - and verify whether testosterone
      is maintained in these cells by androgen receptors (ARs) and/or sex hormone
      binding globulin (SHBG) in winter. Furthermore, regarding the possibility that
      testosterone is converted into estrogen by PGCs in summer, the immunoexpression
      of estrogen receptor (ER)beta was investigated. Bullfrog testes were collected in
      winter and in summer and were embedded in glycol methacrylate for morphological
      analyses or in paraffin for the histochemical detection of AP activity.
      GFRalpha1, AR, SHBG and ERbeta expression were detected by Western blot and
      immunohistochemical analyses. The expression of AP activity and GFRalpha1 in the
      PGCs suggest that these cells are spermatogonial stem cells. In winter, the
      cytoplasmic immunoexpression of ARs and SHBG in the PGCs indicates that
      testosterone is maintained by these proteins in these cells. The cytoplasmic
      immunoexpression of ERbeta, in summer, also points to an ER-mediated action of
      estrogen in PGCs. The results indicate a participation of testosterone and
      estrogen in the control of the primordial spermatogonia during the seasonal
      spermatogenesis of L. catesbeianus.

PMID- 22986370
TI  - Sensory processing issues in young children presenting to an outpatient feeding
      clinic.
AB  - OBJECTIVES: The aim of the study was to describe the relation between sensory
      issues and medical complexity in a series of patients presenting to an outpatient
      multidisciplinary feeding team for evaluation, by a standardized measure of
      sensory-processing abilities. METHODS: A retrospective chart review of all of the
      patients seen from 2004 to 2009 on 2 key variables: medical diagnostic category
      and short sensory profile (SSP) score. RESULTS: On the SSP, 67.6% of children
      scored in the clinical ("definite difference") range. The most common diagnostic
      categories were developmental (n = 23), gastrointestinal (n = 16), and
      neurological (n = 13). Behavioral and cardiorespiratory medical diagnostic
      categories were significantly related to SSP total score and SSP definite
      difference score. CONCLUSIONS: Children who present for feeding evaluation do
      indeed tend to have clinically elevated scores regarding sensory processing, and
      these elevated scores are significantly related to certain medical diagnostic
      categories. Future research is needed to determine why these significant
      relations exist as well as their implications for treatment of feeding-related
      issues.

PMID- 22986371
TI  - Neonatal cholestasis in gram-negative septicaemia.

PMID- 22986374
TI  - Retraction. Two initiation sites of early detection of colon cancer, revealed by
      localization of pERK1/2 in the nuclei or in aggregates at the perinuclear region
      of tumor cells.
AB  - An international independent review was conducted on the above article by the
      editor following a complaint. The expert reviewers agreed that the interpretation
      of the results was not correct. The article is retracted as the results were not
      adequately proven. [the original article was published in the International
      Journal of Oncology 40: 782-788, 2012 DOI: 10.3892/ijo.2011.1268].

PMID- 22986375
TI  - Extracting respiratory information from seismocardiogram signals acquired on the
      chest using a miniature accelerometer.
AB  - Seismocardiography (SCG) is a non-invasive measurement of the vibrations of the
      chest caused by the heartbeat. SCG signals can be measured using a miniature
      accelerometer attached to the chest, and are thus well-suited for unobtrusive and
      long-term patient monitoring. Additionally, SCG contains information relating to
      both cardiovascular and respiratory systems. In this work, algorithms were
      developed for extracting three respiration-dependent features of the SCG signal:
      intensity modulation, timing interval changes within each heartbeat, and timing
      interval changes between successive heartbeats. Simultaneously with a reference
      respiration belt, SCG signals were measured from 20 healthy subjects and a
      respiration rate was estimated using each of the three SCG features and the
      reference signal. The agreement between each of the three accelerometer-derived
      respiration rate measurements was computed with respect to the respiration rate
      derived from the reference respiration belt. The respiration rate obtained from
      the intensity modulation in the SCG signal was found to be in closest agreement
      with the respiration rate obtained from the reference respiration belt: the bias
      was found to be 0.06 breaths per minute with a 95% confidence interval of -0.99
      to 1.11 breaths per minute. The limits of agreement between the respiration rates
      estimated using SCG (intensity modulation) and the reference were within the
      clinically relevant ranges given in existing literature, demonstrating that SCG
      could be used for both cardiovascular and respiratory monitoring. Furthermore,
      phases of each of the three SCG parameters were investigated at four instances of
      a respiration cycle-start inspiration, peak inspiration, start expiration, and
      peak expiration-and during breath hold (apnea). The phases of the three SCG
      parameters observed during the respiration cycle were congruent with existing
      literature and physiologically expected trends.

PMID- 22986377
TI  - Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a
      randomized trial.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder
      of unknown cause with no effective treatment. Cough affects up to 80% of patients
      with IPF, is frequently disabling, and lacks effective therapy. OBJECTIVE: To
      determine the efficacy of thalidomide in suppressing cough in patients with IPF.
      DESIGN: 24-week, double-blind, 2-treatment, 2-period crossover trial.
      (ClinicalTrials.gov registration number: NCT00600028) SETTING: 1 university
      center. PARTICIPANTS: 98 participants were screened, 24 were randomly assigned,
      23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4%
      predicted), and 20 completed both treatment periods. MEASUREMENTS: The primary
      end point was cough-specific quality of life measured by the Cough Quality of
      Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of
      cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures,
      lower scores equaled improved cough or respiratory quality of life. RESULTS: CQLQ
      scores significantly improved with thalidomide (mean difference vs. placebo, 
      11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved
      scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2
      [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores
      from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved
      compared with those of participants receiving placebo. Adverse events were
      reported in 74% of patients receiving thalidomide and 22% receiving placebo;
      constipation, dizziness, and malaise were more frequent with thalidomide.
      LIMITATION: This was a single-center study of short duration and small sample
      size focused on symptom-specific quality of life. CONCLUSION: Thalidomide
      improved cough and respiratory quality of life in patients with IPF. A larger
      trial is warranted to assess these promising results. PRIMARY FUNDING SOURCE:
      Celgene Corporation.

PMID- 22986376
TI  - Development and validation of a coronary risk prediction model for older U.S. and
      European persons in the Cardiovascular Health Study and the Rotterdam Study.
AB  - BACKGROUND: Risk scores for prediction of coronary heart disease (CHD) in older
      adults are needed. OBJECTIVE: To develop a sex-specific CHD risk prediction model
      for older adults that accounts for competing risks for death. DESIGN: 2
      observational cohort studies, using data from 4946 participants in the
      Cardiovascular Health Study (CHS) and 4303 participants in the Rotterdam Study
      (RS). SETTING: Community settings in the United States (CHS) and Rotterdam, the
      Netherlands (RS). PARTICIPANTS: Persons aged 65 years or older who were free of
      cardiovascular disease. MEASUREMENTS: A composite of nonfatal myocardial
      infarction and coronary death. RESULTS: During a median follow-up of 16.5 and
      14.9 years, 1166 CHS and 698 RS participants had CHD events, respectively. Deaths
      from noncoronary causes largely exceeded the number of CHD events, complicating
      accurate CHD risk predictions. The prediction model had moderate ability to
      discriminate between events and nonevents (c-statistic, 0.63 in both U.S. and
      European men and 0.67 and 0.68 in U.S. and European women). The model was well
      calibrated; predicted risks were in good agreement with observed risks. Compared
      with the Framingham point scores, the prediction model classified elderly U.S.
      persons into higher risk categories but elderly European persons into lower risk
      categories. Differences in classification accuracy were not consistent and
      depended on cohort and sex. Adding newer cardiovascular risk markers to the model
      did not substantially improve performance. LIMITATION: The model may be less
      applicable in nonwhite populations, and the comparison Framingham model was not
      designed for adults older than 79 years. CONCLUSION: A CHD risk prediction model
      that accounts for deaths from noncoronary causes among older adults provided well
      calibrated risk estimates but was not substantially more accurate than Framingham
      point scores. Moreover, adding newer risk markers did not improve accuracy. These
      findings emphasize the difficulties of predicting CHD risk in elderly persons and
      the need to improve these predictions. PRIMARY FUNDING SOURCE: National Heart,
      Lung, and Blood Institute; National Institute of Neurological Disorders and
      Stroke; The Netherlands Organisation for Scientific Research; and the Netherlands
      Organisation for Health Research and Development.

PMID- 22986378
TI  - Transitional care after hospitalization for acute stroke or myocardial
      infarction: a systematic review.
AB  - BACKGROUND: Transitional care is a time-limited service to prevent discontinuous
      care and adverse outcomes, including rehospitalization. PURPOSE: To describe
      transitional care interventions and evidence of benefit or harm in patients
      hospitalized for acute stroke or myocardial infarction (MI). DATA SOURCES:
      Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Cochrane
      Database of Systematic Reviews, and EMBASE, supplemented with manual searches of
      reference lists of relevant studies and review articles (January 2000 to March
      2012). STUDY SELECTION: 6 reviewers screened 5857 citations to identify English
      language reports of trials or observational studies that compared transitional
      care with usual care among adults hospitalized for stroke or MI and that reported
      patient, caregiver, process, or systems outcomes within 1 year of hospital
      discharge. DATA EXTRACTION: Data on study design, quality, population,
      intervention characteristics, and patient- and system-level outcomes were
      extracted by 3 reviewers and confirmed by 1 additional reviewer. DATA SYNTHESIS:
      62 articles representing 44 studies of transitional care for either acute stroke
      (27 studies) or MI (17 studies). Four intervention types were studied: hospital
      initiated support (n = 14), patient and family education (n = 7), community-based
      support (n = 20), and chronic disease management (n = 3). Most studies (68%) were
      of fair quality. Overall, moderate-strength evidence showed that hospital
      initiated support reduced length of stay for patients who had a stroke, and low
      strength evidence showed that it reduced mortality for patients who had an MI.
      Evidence about benefits of other interventions and harms from transitional care
      services was insufficient. LIMITATIONS: Few studies had high-quality research
      designs. The usual care comparator was often poorly defined. Applicability to
      U.S. clinical practice was limited; only 6 studies were conducted in the United
      States. CONCLUSION: Available evidence shows that hospital-initiated transitional
      care can improve some outcomes in adults hospitalized for stroke or MI. Finding
      additional transitional care interventions that improve functional outcomes and
      prevent rehospitalizations and adverse events is a high priority for the growing
      population of patients who have an MI or a stroke. PRIMARY FUNDING SOURCE: Agency
      for Healthcare Research and Quality.

PMID- 22986379
TI  - Improving patient handovers from hospital to primary care: a systematic review.
AB  - BACKGROUND: Evidence shows that suboptimum handovers at hospital discharge lead
      to increased rehospitalizations and decreased quality of health care. PURPOSE: To
      systematically review interventions that aim to improve patient discharge from
      hospital to primary care. DATA SOURCES: PubMed, CINAHL, PsycInfo, the Cochrane
      Library, and EMBASE were searched for studies published between January 1990 and
      March 2011. STUDY SELECTION: Randomized, controlled trials of interventions that
      aimed to improve handovers between hospital and primary care providers at
      hospital discharge. DATA EXTRACTION: Two reviewers independently abstracted data
      on study objectives, setting and design, intervention characteristics, and
      outcomes. Studies were categorized according to methodological quality, sample
      size, intervention characteristics, outcome, statistical significance, and
      direction of effects. DATA SYNTHESIS: Of the 36 included studies, 25 (69.4%) had
      statistically significant effects in favor of the intervention group and 34
      (94.4%) described multicomponent interventions. Effective interventions included
      medication reconciliation; electronic tools to facilitate quick, clear, and
      structured summary generation; discharge planning; shared involvement in follow
      up by hospital and community care providers; use of electronic discharge
      notifications; and Web-based access to discharge information for general
      practitioners. Statistically significant effects were mostly found in reducing
      hospital use (for example, rehospitalizations), improvement of continuity of care
      (for example, accurate discharge information), and improvement of patient status
      after discharge (for example, satisfaction). LIMITATIONS: Heterogeneity of the
      interventions and study characteristics made meta-analysis impossible. Most
      studies had diffuse aims and poor descriptions of the specific intervention
      components. CONCLUSION: Many interventions have positive effects on patient care.
      However, given the complexity of interventions and outcome measures, the
      literature does not permit firm conclusions about which interventions have these
      effects. PRIMARY FUNDING SOURCE: The European Union, the Framework Programme of
      the European Commission.

PMID- 22986380
TI  - Transitional care: focusing on patient-centered outcomes and simplicity.

PMID- 22986381
TI  - My magnanimous mentor.

PMID- 22986383
TI  - Letters from the grave.

PMID- 22986384
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986385
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986386
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986387
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986388
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986389
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986390
TI  - Dialogue on geriatrics: how should we fix the problem?

PMID- 22986392
TI  - Antidiuretic hormone antagonist to reduce cystine stone formation.

PMID- 22986393
TI  - Summaries for patients. Thalidomide treatment for cough in patients with
      idiopathic pulmonary fibrosis.

PMID- 22986394
TI  - ACP Journal Club. Review: new oral anticoagulants reduced stroke and systemic
      embolism compared with warfarin in AF.

PMID- 22986395
TI  - ACP Journal Club. Flexible sigmoidoscopy screening reduced colorectal cancer
      incidence and mortality in older adults.

PMID- 22986396
TI  - ACP Journal Club. Review: teriparatide reduces fractures in postmenopausal women
      with osteoporosis.

PMID- 22986397
TI  - ACP Journal Club. Review: oseltamivir relieves symptoms but does not reduce
      hospitalizations in influenza.

PMID- 22986398
TI  - ACP Journal Club. Review: CT screening for lung cancer reduced mortality in 1
      large trial but not in 2 smaller trials.

PMID- 22986399
TI  - ACP Journal Club. Review: varenicline is better than bupropion but not nicotine
      patch for smoking abstinence in adults.

PMID- 22986400
TI  - ACP Journal Club. Telemonitoring did not reduce hospitalizations or ED visits in
      high-risk elderly patients.

PMID- 22986401
TI  - ACP Journal Club. Short-term was less effective than long-term flecainide for
      preventing recurrent AF after cardioversion.

PMID- 22986402
TI  - ACP Journal Club. Glargine did not reduce CV events more than standard care in
      patients with dysglycemia.

PMID- 22986403
TI  - ACP Journal Club. Daily n-3 fatty acid supplements did not reduce CV events in
      high-risk patients with dysglycemia.

PMID- 22986404
TI  - ACP Journal Club. CBT by telephone for depression improved adherence compared
      with face-to-face CBT in primary care.

PMID- 22986405
TI  - ACP Journal Club. Citicoline did not improve recovery at 90 days after moderate
      to-severe acute ischemic stroke.

PMID- 22986406
TI  - Multiple isoforms of CDC25 oppose ATM activity to maintain cell proliferation
      during vertebrate development.
AB  - The early development of vertebrate embryos is characterized by rapid cell
      proliferation necessary to support the embryo's growth. During this period, the
      embryo must maintain a balance between ongoing cell proliferation and mechanisms
      that arrest or delay the cell cycle to repair oxidative damage and other
      genotoxic stresses. The ataxia-telangiectasia mutated (ATM) kinase is a critical
      regulator of the response to DNA damage, acting through downstream effectors,
      such as p53 and checkpoint kinases (CHK) to mediate cell-cycle checkpoints in the
      presence of DNA damage. Mice and humans with inactivating mutations in ATM are
      viable but have increased susceptibility to cancers. The possible role of ATM in
      limiting cell proliferation in early embryos has not been fully defined. One
      target of ATM and CHKs is the Cdc25 phosphatase, which facilitates cell-cycle
      progression by removing inhibitory phosphates from cyclin-dependent kinases
      (CDK). We have identified a zebrafish mutant, standstill, with an inactivating
      mutation in cdc25a. Loss of cdc25a in the zebrafish leads to accumulation of
      cells in late G(2) phase. We find that the novel family member cdc25d is
      essential for early development in the absence of cdc25a, establishing for the
      first time that cdc25d is active in vivo in zebrafish. Surprisingly, we find that
      cell-cycle progression in cdc25a mutants can be rescued by chemical or genetic
      inhibition of ATM. Checkpoint activation in cdc25a mutants occurs despite the
      absence of increased DNA damage, highlighting the role of Cdc25 proteins to
      balance constitutive ATM activity during early embryonic development.

PMID- 22986407
TI  - How a common variant in the growth factor receptor gene, NTRK1, affects white
      matter.
AB  - Growth factors and their receptors are important for cellular migration as well
      as axonal guidance and myelination in the brain. They also play a key role in
      programmed cell death, and are implicated in a number of mental illnesses.
      Recently, we reported that healthy young adults who carry the T allele variant in
      the growth factor gene, NTRK1 (at location rs6336), had lower white matter
      integrity than non-carriers on diffusion images of the brain. Diffusion tensor
      imaging (DTI) revealed how this single nucleotide polymorphism affects white
      matter microstructure in human populations; DTI is also used to identify
      characteristic features of brain connectivity in typically developing children
      and in patients. Newly discovered links between neuroimaging measures and growth
      factors whose molecular neuroscience is well known offer an important step in
      understanding mechanisms that contribute to brain connectivity. Altered fiber
      connectivity may mediate the relationship between some genetic risk factors and a
      variety of mental illnesses. 

PMID- 22986408
TI  - Substrate generation for endonucleases of CRISPR/cas systems.
AB  - The interaction of viruses and their prokaryotic hosts shaped the evolution of
      bacterial and archaeal life. Prokaryotes developed several strategies to evade
      viral attacks that include restriction modification, abortive infection and
      CRISPR/Cas systems. These adaptive immune systems found in many Bacteria and most
      Archaea consist of clustered regularly interspaced short palindromic repeat
      (CRISPR) sequences and a number of CRISPR associated (Cas) genes (Fig. 1) (1-3).
      Different sets of Cas proteins and repeats define at least three major divergent
      types of CRISPR/Cas systems (4). The universal proteins Cas1 and Cas2 are
      proposed to be involved in the uptake of viral DNA that will generate a new
      spacer element between two repeats at the 5' terminus of an extending CRISPR
      cluster (5). The entire cluster is transcribed into a precursor-crRNA containing
      all spacer and repeat sequences and is subsequently processed by an enzyme of the
      diverse Cas6 family into smaller crRNAs (6-8). These crRNAs consist of the spacer
      sequence flanked by a 5' terminal (8 nucleotides) and a 3' terminal tag derived
      from the repeat sequence (9). A repeated infection of the virus can now be
      blocked as the new crRNA will be directed by a Cas protein complex (Cascade) to
      the viral DNA and identify it as such via base complementarity(10). Finally, for
      CRISPR/Cas type 1 systems, the nuclease Cas3 will destroy the detected invader
      DNA (11,12) . These processes define CRISPR/Cas as an adaptive immune system of
      prokaryotes and opened a fascinating research field for the study of the involved
      Cas proteins. The function of many Cas proteins is still elusive and the causes
      for the apparent diversity of the CRISPR/Cas systems remain to be illuminated.
      Potential activities of most Cas proteins were predicted via detailed
      computational analyses. A major fraction of Cas proteins are either shown or
      proposed to function as endonucleases (4). Here, we present methods to generate
      crRNAs and precursor-cRNAs for the study of Cas endoribonucleases. Different
      endonuclease assays require either short repeat sequences that can directly be
      synthesized as RNA oligonucleotides or longer crRNA and pre-crRNA sequences that
      are generated via in vitro T7 RNA polymerase run-off transcription. This
      methodology allows the incorporation of radioactive nucleotides for the
      generation of internally labeled endonuclease substrates and the creation of
      synthetic or mutant crRNAs. Cas6 endonuclease activity is utilized to mature pre
      crRNAs into crRNAs with 5'-hydroxyl and a 2',3'-cyclic phosphate termini.

PMID- 22986409
TI  - Introduction.

PMID- 22986410
TI  - A new translocation t(1p;18) in an Italian Mediterranean river buffalo (Bubalus
      bubalis, 2n = 50) bull: cytogenetic, fertility and inheritance studies.
AB  - In recent years increasing attention has been paid to the cytogenetic control of
      Italian Mediterranean river buffalo (BBU) bulls authorized as sires which are
      registered in the stud book. Chromosome abnormalities described in this species
      are mainly numerical and affecting sex chromosomes. During routine cytogenetic
      analyses performed on young Italian Mediterranean river buffalo bulls in the
      progeny test, 1 animal was found to be carrier of a never before reported
      translocation t(1p;18) originated by fission of BBU1 and subsequent centric
      fusion of BBU1p with BBU18 as demonstrated by both R-banding and FISH-mapping
      techniques using specific molecular markers of BBU1p (DEFB1) and BBU18 (GPI).
      According to sperm analyses the semen characteristics were in physiological
      ranges, but the calf crop percentage was only 48.77% instead of 70-80%.
      Cytogenetic analyses performed on 50 offspring (36 females and 14 males) showed
      that 15 of them (30%) were carriers of the same translocation.

PMID- 22986411
TI  - An unusual double T5(2) water tape trapped in silver(I) coordination polymer
      hosts: influence of the solvent on the assembly of Ag(I)-4,4'-bipyridine chains
      with trans-cyclohexanedicarboxylate and their luminescent properties.
AB  - In this paper, four silver(I) compounds, namely,
      {[Ag(4)(bipy)(4)(chda)].2NO(3).10H(2)O}(n) (1),
      {[Ag(2)(bipy)(2)(chda)].14H(2)O}(n) (2), {[Ag(2)(bipy)(2)(chda)].3EG.2H(2)O}(n)
      (3) and {[Ag(2)(bipy)(2)(chda)].H(2)chda}(n) (4) (where bipy = 4,4'-bipyridine,
      H(2)chda = trans-cyclohexane-dicarboxylate and EG = ethylene glycol), have been
      synthesized and characterized by single-crystal X-ray diffraction analyses. In
      all of these compounds, the Ag(I) centers are linked by bipy ligands to form 1D
      Ag(I)-bipy chain structures. The chda(2-) anions of compound 1 adopt a MU(4)
      coordination mode to connect the Ag(I)-bipy chains, forming a H-beam-like chain.
      In 2, the chda(2-) anions adopt a MU(2)-coordination mode to connect the Ag(I)
      bipy chains resulting in two distinct 2D brick wall-like layers. These layers are
      further stacked in an ...ABAB... fashion through interlayer pi...pi stacking
      interactions giving rise to a 3D framework consisting of quasi-rectangular
      channels, in which an unusual double T5(2) water tape is trapped. For 3 and 4,
      the chda(2-) anions show a similar MU(4)-coordination mode to that of 1 and
      connect the Ag(I)-bipy chains to form 2D grid layers with identical compositions
      and connective topologies. The experimental studies show that the final
      structures are greatly influenced by the molar ratio of the components and the
      solvents, which can be rationally interpreted by the existence of various
      supramolecular interactions between the host and guest molecules within these
      compounds through a systematic structural comparison. Additionally, the thermal
      stability and luminescent properties of these compounds were also studied.

PMID- 22986412
TI  - Neuromodulatory role of melatonin in retinal information processing.
AB  - The neurohormone melatonin is implicated in a variety of physiological processes.
      In the retina, a major source for melatonin production, melatonin is involved in
      modulation of neuronal activities. In this article we review recent advances in
      this research field, which is preceded by a concise account of general
      information about melatonin, melatonin receptors and intracellular signaling
      pathways for melatonin actions. Melatonin is mainly synthesized in and released
      from photoreceptors in the retina. Different subtypes of melatonin receptors are
      present on major types of retinal neurons, and the expression of these receptors
      is highly species- and neuron subtype-dependent. By activating different
      melatonin receptor subtypes, melatonin modulates activities of retinal neurons.
      In the outer retina, melatonin regulates the activity of photoreceptors. In
      addition, melatonin reduces the light responsiveness of cone-driven horizontal
      cells, but potentiates rod signal to rod-dominant ON type bipolar cells in
      teleost fish or inhibits the TEA-sensitive potassium channel of rod-driven ON
      type bipolar cells in rats. In the inner retina, melatonin potentiates inputs
      from glycinergic amacrine cells to ganglion cells in rats. These actions of
      melatonin on retinal neurons are mediated by distinct intracellular signaling
      pathways via different subtypes of melatonin receptors and all serve to improve
      visual performance in a world of changing ambient illumination. The topics,
      concerning allosteric action of melatonin, interplay between melatonin and
      dopamine systems, and potential interaction between melatonin and melanopsin
      systems, are also discussed. An in-depth discussion of future directions in this
      research field is presented.

PMID- 22986413
TI  - Potential of dosage reduction in cone-beam-computed tomography (CBCT) for
      radiological diagnostics of the paranasal sinuses.
AB  - More than 10 years ago, cone-beam-computed tomography (CBCT) was introduced in
      ENT radiology. Until now, the focus of research was to evaluate clinical limits
      of this technique. The aim of this work is the evaluation of specific dosages and
      the identification of potential optimization in the performance of CBCT of the
      paranasal sinuses. Based on different tube parameters (tube current, tube
      voltage, and rotation angles), images of the nose and the paranasal sinuses were
      taken on a phantom head with the Accu-I-tomo F17 (Morita, Kyoto, Japan). The
      dosages applied to the lens and parotid gland were measured with OSL dosimetry.
      The imaging quality was evaluated by independent observers. All datasets were
      reviewed according to a checklist of surgically important anatomic structures.
      Even for lowest radiation exposure (4 mA, 76 kV, 180 degrees , computed
      tomography dosage index (CTDI) = 1.8 mGy), the imaging quality was sufficient. Of
      course a significant reduction of the imaging quality could be seen, so a
      reliable mean was set for 4 mA, 84 kV, and 180 degrees  rotation angle (CTDI =
      2.4 mGy). In this combination, a reduction of 92 % in lens-dose and of 77 % of
      dosage at the parotid gland was observed in comparison to the maximal possible
      adjustments (8 mA, 90 kV, 360 degrees , CTDI = 10.9 mGy). There is potential for
      optimization in CBCT. Changing the rotation angle (180 degrees  instead of 360
      degrees ) leads to a dose reduction of 50 %. Furthermore from clinical point of
      view in case of chronic rhinosinusitis a relevant reduction of dosage is
      possible. Therefore, it is necessary to intensify the interdisciplinary
      discussion about the disease specifics required quality of imaging.

PMID- 22986414
TI  - Using a linear stapler for pharyngeal closure in total laryngectomy.
AB  - This study aimed to evaluate the value of using a linear stapler device in total
      laryngectomy using a prospective study. Twenty-one total laryngectomies were
      performed from August 2010 to April 2012, using TA-60 linear stapler for
      pharyngeal closure. Data collected included age, sex, staging, surgical margins
      and postoperative course (including complications and swallowing). Patients
      comprised twenty men and one woman. The mean age was 64 years. Two patients
      underwent preoperative radiotherapy. Four patients recurred after radiotherapy.
      Fifteen patients were untreated. Negative surgical margins were achieved in all
      patients. One patient developed slight pharyngocutaneous fistula. Patients
      resumed oral intake at 7 days. The mean hospital stay was 10 days. Using a linear
      stapler to close laryngopharyngeal cavity in total laryngectomy is simple,
      reliable and practical, avoids pollution of surgical area, saves operation time
      and decreases the incidence of pharyngocutaneous fistula. It is worthy of
      clinical application for selected cases.

PMID- 22986415
TI  - Descending necrotizing mediastinitis from deep neck infection.
AB  - This study aims to identify predisposing characteristics of descending
      necrotizing mediastinitis (DNM) arising from deep neck infection (DNI) and to
      determine appropriate therapeutic intervention strategies. We retrospectively
      reviewed 54 patients (male, n = 34; female, n = 20; mean age, 64.5 years) who had
      been treated at Mie University Hospital for DNI between April 2001 and October
      2011. Eight of nine patients who developed DNM confirmed by computed tomography
      of the neck and chest, underwent mediastinal drainage (video-assisted thoracic
      surgical drainage, n = 6; mediastinoscopy-assisted drainage, n = 2). A patient
      developed uncontrolled acute respiratory distress syndrome after aggressive
      surgery, resulting in a mortality rate of 12 %. High blood CRP values, and the
      pharynx and tonsils as origins of infection were factors involved in the
      development of DNM arising from DNI. In conclusion, DNM remains a destructive and
      fatal disease that requires aggressive treatment including mediastinal
      exploration.

PMID- 22986416
TI  - Reduced number of circulating endothelial progenitor cells (CD133+/KDR+) in
      patients with plaque psoriasis.
AB  - BACKGROUND: Psoriasis is associated with an increased cardiovascular risk.
      Circulating endothelial progenitor cells (CEPCs) play a significant role in the
      maintenance of vascular homeostasis. OBJECTIVE: The aim of this study was to
      evaluate the number of CEPCs in patients with psoriasis compared to controls and
      assess possible correlations between the number of these cells and the plasma
      levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial
      growth factor receptor-1 (sVEGFR-1) and clinical features of psoriasis. METHODS:
      The number of CEPCs, identified as CD133+/KDR+ cells, was determined with flow
      cytometry in peripheral blood of psoriatic patients (n = 63) and controls (n =
      31). The plasma levels of VEGF and sVEGFR-1 were measured with enzyme-linked
      immunosorbent assay. RESULTS: The number of CEPCs was significantly reduced in
      psoriatic patients compared with controls (p = 0.000026) and inversely correlated
      with disease severity (R = -0.283; p = 0.0248). CONCLUSION: A reduced number of
      CEPCs may contribute to endothelial dysfunction in patients with psoriasis.

PMID- 22986417
TI  - Myocardial protection by glucose-insulin-potassium in acute coronary syndrome
      patients undergoing urgent multivessel off-pump coronary artery bypass surgery.
AB  - BACKGROUND: The aim of this randomized and controlled trial was to investigate
      the effect of a glucose-insulin-potassium (GIK) solution on myocardial protection
      in acute coronary syndrome (ACS) patients undergoing urgent multivessel off-pump
      coronary artery bypass (OPCAB) surgery. METHODS: Sixty-six patients were randomly
      allocated either to receive 0.3 ml kg(-1) h(-2) GIK solution (potassium 80 mEq
      and regular insulin 325 IU in 500 ml of 50% glucose) or equivalent volume of
      normal saline (control) upon anaesthetic induction until 6 h after reperfusion.
      The primary endpoints were to compare the concentrations of creatine kinase-MB
      (CK-MB) and troponin-T between the groups after reperfusion. The secondary
      endpoints were to compare the incidences of postoperative troponin-T >0.8 ng ml(
      1) and myocardial infarction (MI) between the groups. RESULTS: Highest CK-MB [8.7
      (4.4) vs 13.1 (7.9) ng ml(-1), P=0.006] and troponin-T [0.20 (0.13-0.49) vs 0.48
      (0.18-0.91) ng ml(-1), P<0.0001] values after reperfusion were significantly
      lower in the GIK group compared with the control group. The area under the curve
      of serially measured troponin-T was also significantly smaller in the GIK group
      compared with the control group [0.83 (0.43-1.81) vs 0.46 (0.31-1.00), P=0.036].
      Significantly fewer patients in the GIK group showed troponin-T >0.8 ng ml(-1)
      after reperfusion compared with the control group (3 vs 11, P=0.033). The
      incidence of postoperative MI was similar between the groups. CONCLUSIONS: GIK
      administration in ACS patients undergoing urgent multivessel OPCAB significantly
      attenuated the degree of ensuing myocardial injury without complications related
      to glycaemic control. Clinical Trial Registry. URL:
      http://clinicaltrials.gov/ct2/show/NCT01384656?term=GIK+AND+OPCAB&rank=1. Unique
      identification number NCT01384656.

PMID- 22986418
TI  - Single-breath vital capacity high concentration sevoflurane induction in
      children: with or without nitrous oxide?
AB  - BACKGROUND: Single-breath vital capacity inhalation induction with high
      concentration sevoflurane (SBVC-HC) is a rapid and 'needleless' technique,
      preferred and well tolerated in the cooperative child. The addition of nitrous
      oxide may speed up induction by its second gas effects. Previous studies done in
      children looking at the effect of N(2)O on this technique lacked power and showed
      conflicting results. This study aims to investigate the effect of N(2)O on
      induction time for SBVC-HC sevoflurane induction in children. METHODS: Eighty
      unpremedicated, ASA I and II children, aged 5-15 yr having elective surgical
      procedures under general anaesthesia, were recruited and randomized to: Group A:
      8% sevoflurane in O(2) 6 litre min(-1), and Group B: 8% sevoflurane in N(2)O 4
      litre min(-1) and O(2) 2 litre min(-1). The primary outcome was the time to 'loss
      of eyelash reflex'. The time to return of 'regular respiration' and 'conjugate
      gaze' were also noted. RESULTS: The difference in the 'time to loss of eyelash
      reflex' was small but statistically significant. Group B: mean duration 53.6 s,
      standard deviation (SD) 16.1, compared with Group A: 63.5 s, SD 16.1 (mean
      difference 9.9, 95% confidence interval 2.5-17.3, P=0.01). Differences in the
      time to return of 'regular breathing' and 'conjugate gaze' were not statistically
      significant. Patients receiving N(2)O had less excitatory movements (P=0.007),
      but incidence of other adverse events was low and did not differ significantly
      between both groups. More than 94% of children would choose this method of
      induction again in both groups. CONCLUSIONS: We conclude that for SBVC-HC
      sevoflurane induction in children, the addition of N(2)O resulted in faster loss
      of consciousness and reduced excitatory movements.

PMID- 22986419
TI  - Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary
      bypass and convulsive seizures: incidence and clinical outcome.
AB  - BACKGROUND: Convulsive seizures (CS) occur in ~1% of the patients after cardiac
      surgery with cardiopulmonary bypass. Recent investigations indicate an up to
      seven-fold increase in CS in cardiac surgical patients receiving high doses (>=60
      mg kg(-1) body weight) of tranexamic acid (TA). METHODS: In a retrospective data
      analysis of 4883 cardiac surgical patients, we investigated the incidence of CS
      in patients receiving a moderate dose of TA (24 mg kg(-1) body weight) compared
      with a reference group not receiving TA as a primary endpoint. Secondary
      endpoints were intensive care unit stay and in-hospital mortality. We performed
      propensity score (PS)-adjusted logistic regression analysis to test the
      association between TA use/non-use and clinical outcomes. RESULTS: Compared with
      the reference group, the PS-adjusted odds ratio (OR) for CS in the TA group was
      1.703 [95% confidence interval (CI): 1.01-2.87; P=0.045; incidence 2.5% vs 1.2%].
      Log-ICU-stay was significantly longer (P=0.004) and PS-adjusted relative in
      hospital mortality risk was significantly higher for the TA group compared with
      the reference group (OR=1.89; 95% CI: 1.21-2.96; P=0.005). Both the TA-associated
      CS incidence and the in-hospital mortality risk were only significant in patients
      undergoing open-heart surgery (OR=2.034, 95% CI: 1.07-3.87; P=0.034 and OR=2.20,
      95% CI: 1.32-3.69; P=0.003, respectively) but not in patients undergoing coronary
      artery bypass grafting (OR=1.21, 95% CI: 0.49-3.03; P=0.678 and OR=1.13, 95% CI:
      0.42-3.02; P=0.809, respectively). CONCLUSIONS: In open-heart surgery, even
      moderate TA doses are associated with a doubled rate of CS and in-hospital
      mortality. Prospective trials are needed to further evaluate the safety profile
      of TA in cardiac surgery.

PMID- 22986420
TI  - Effect of high-dose preoperative methylprednisolone on recovery after total hip
      arthroplasty: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: High-dose glucocorticoid may reduce postsurgical pain and improve
      recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time
      to meet functional discharge criteria after total hip arthroplasty (THA).
      METHODS: Forty-eight patients undergoing unilateral THA under spinal anaesthesia
      were consecutively included in this randomized, double-blind, placebo-controlled
      trial receiving preoperative i.v. MP or saline. All patients received a
      standardized, multimodal analgesic regime with paracetamol, celecoxib, and
      gabapentin. The primary outcome was time to meet well-defined functional
      discharge criteria. Secondary outcomes were handgrip strength and endurance,
      pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic
      , and hypnotic medicine requirements. The inflammatory response measured by C
      reactive protein (CRP) and actual length of stay were also registered. Discharge
      criteria were assessed twice daily (at 09:00 and 14:00 h) until discharge. Other
      outcomes were assessed at 2, 4, 6, 8, and 24 h after operation, and also in a
      questionnaire from postoperative day (POD) 1-4. RESULTS: Time to meet discharge
      criteria was [median (IQR) (95% CI), MP vs placebo]: 23.5 (23.3-23.7) (17.8-43.8)
      vs 23.5 (23.0-23.8) (20.0-46.8) h, the mean difference (95% CI) being -1.3 (-4.7
      to 2.2) h, P=0.65. Overall pain for the first 24 h after surgery was
      significantly reduced in the MP vs the placebo group (P<0.01), as was CRP at 24 h
      (P<0.0001). No other between-group differences were observed. No drug-related
      complications were observed at follow-up on POD30. CONCLUSIONS: MP 125 mg i.v.
      before surgery added to a multimodal oral analgesic regime did not reduce time to
      meet functional discharge criteria after THA, but improved analgesia for the
      first 24 h.

PMID- 22986421
TI  - Failed tracheal intubation in obstetric anaesthesia: 2 yr national case-control
      study in the UK.
AB  - BACKGROUND: There are few national figures on the incidence of failed tracheal
      intubation during general anaesthesia in obstetrics. Recent small studies have
      quoted a rate of one in 250 general anaesthetics (GAs). The aim of this UK
      national study was to estimate this rate and identify factors that may be
      predictors. METHODS: Using the UK Obstetric Surveillance System (UKOSS) of data
      collection, a survey was conducted between April 2008 and March 2010. Incidence
      and associated risk factors were recorded in consultant-led UK delivery suites.
      Units reported the details of any failed intubation (index case) and the two
      preceding GA cases (controls). Predictors were evaluated using multivariable
      logistic regression, significance P<0.05 (two-sided). RESULTS: We received 57
      completed reports (100% response). The incidence using a unit-based estimation
      approach was one in 224 (95% confidence interval 179-281). Univariate analyses
      showed the index cases to be significantly older, heavier, with higher BMI, with
      Mallampati score recorded and score >1. Multivariate analyses showed that age,
      BMI, and a recorded Mallampati score were significant independent predictors of
      failed tracheal intubation. The classical laryngeal mask airway was the most
      commonly used rescue airway (39/57 cases). There was one emergency surgical
      airway but no deaths or hypoxic brain injuries. Gastric aspiration occurred in
      four (8%) index cases. Index cases were more likely to have maternal morbidities
      (P=0.026) and many babies in both groups were admitted to the neonatal intensive
      care unit: 21 (37%) vs 29 (27%) (NS). Three babies died--all in the control
      group.

PMID- 22986422
TI  - Chiral transformations of achiral porous metal-organic frameworks via a stepwise
      approach.
AB  - A family of chiral porous metal-organic frameworks were synthesized through an
      unprecedented chiral transformation process only involving achiral components.
      This method may provide a new point of view to rationally design targeted chiral
      MOFs and may shed light on the symmetry breaking mechanism.

PMID- 22986423
TI  - Reduced arterial stiffness in patients with acromegaly: non-invasive assessment
      by the cardio-ankle vascular index (CAVI).
AB  - In patients with acromegaly, cardiovascular diseases are the most common cause of
      death.  Arterial stiffness is increasingly recognized as a valuable surrogate
      marker for predicting cardiovascular events. To evaluate the vascular status of
      acromegalic patients, we used the cardio-ankle vascular index (CAVI) to reflect
      the arterial stiffness from the heart to the ankles. We analyzed 21 acromegalic
      patients, comprising five patients with untreated active acromegaly, one patient
      treated with medication and 15 patients who underwent transsphenoidal surgery.
      Among the 15 patients with surgery, 10 received additional therapies with
      dopamine agonists and/or somatostatin analogs.  All patients with acromegaly
      unexpectedly showed significant reductions in the CAVI, indicating reduced
      arterial stiffness, compared with age- and sex-matched controls, regardless of
      whether they underwent surgery.  There was a significant negative correlation
      between the CAVI and the serum insulin-like growth factor (IGF)-I level in these
      patients.  Active acromegalic patients were associated with lower CAVI than
      controlled patients.  Sequential measurements of the CAVI and serum IGF-I before
      and after treatment with octreotide and transsphenoidal surgery revealed that a
      reduced IGF-I level after treatment was accompanied by CAVI elevation.  The
      present findings indicate that the CAVI is negatively correlated with the serum
      IGF-I level in acromegaly.  These findings are consistent with previous reports
      indicating that the GH/IGF-I axis reduces peripheral vascular resistance.  This
      non-invasive assessment can reflect the present vascular status and would be a
      useful marker for evaluation of therapeutic effects in patients with acromegaly.

PMID- 22986424
TI  - "Unequivocally Abnormal" vs "Usual" Signs and Symptoms for Proficient Diagnosis
      of Diabetic Polyneuropathy: Cl vs N Phys Trial.
AB  - OBJECTIVE To repeat the Clinical vs Neurophysiology (Cl vs N Phys) trial using
      "unequivocally abnormal" signs and symptoms (Trial 2) compared with the earlier
      trial (Trial 1), which used "usual" signs and symptoms. DESIGN Standard and
      referenced nerve conduction abnormalities were used in both Trials 1 and 2 as the
      standard criterion indicative of diabetic sensorimotor polyneuropathy. Physician
      proficiency (accuracy among evaluators) was compared between Trials 1 and 2.
      SETTING Academic medical centers in Canada, Denmark, England, and the United
      States. PARTICIPANTS Thirteen expert neuromuscular physicians. One expert was
      replaced in Trial 2. RESULTS The marked overreporting, especially of signs, in
      Trial 1 was avoided in Trial 2. Reproducibility of diagnosis between days 1 and 2
      was significantly (P = .005) better in Trial 2. The correlation of the following
      clinical scores with composite nerve conduction measures spanning the range of
      normality and abnormality was improved in Trial 2: pinprick sensation (P = .03),
      decreased reflexes (P = .06), touch-pressure sensation (P = .06), and the sum of
      symptoms (P = .06). CONCLUSIONS The simple pretrial decision to use unequivocally
      abnormal signs and symptoms-taking age, sex, and physical variables into account
      in making clinical judgments for the diagnosis of diabetic sensorimotor
      polyneuropathy (Trial 2) improves physician proficiency compared with use of
      usual elicitation of signs and symptoms (Trial 1); both compare to confirmed
      nerve conduction abnormality.

PMID- 22986425
TI  - Isocyanate exposure control in motor vehicle paint spraying: evidence from
      biological monitoring.
AB  - AIMS: The purpose of this work was to assess the changes in control of exposure
      to hexamethylene diisocyanate based paints used in vehicle spraying after a
      Health & Safety Executive (HSE) national project. METHODS: Paint sprayers and
      managers from motor vehicle repair (MVR) bodyshops across the UK, were invited to
      one of 32 Safety and Health Awareness Days (SHADs) to increase their
      understanding of the hazards, and practical ways of controlling of exposure to
      isocyanate based paints. Exposure measurement based on biological monitoring was
      offered, free of charge, to each of the roughly 4000 participants and used to
      assess the effectiveness of controls and methods of working. Results are compared
      with pre and post SHAD measurements. RESULTS: Urine samples were received from
      995 paint sprayers. Hexamethylene diamine (HDA) levels in urine, indicative of
      exposure to hexamethylene diisocyanate (HDI), were significantly lower (Mann
      Whitney, p<0.0001) than had been seen in a wider population from previous HSE
      inspections and routine sampling. Where a sprayer's urinary HDA was above the
      quantification limit they were asked to send another sample after reviewing and
      improving exposure control measures. The results from these repeat samples were
      significantly lower than the original results. There was no difference in the
      exposures of sprayers using air-fed half-mask face-pieces compared with visor
      type air-fed breathing apparatus, or between spray booths and rooms. CONCLUSIONS:
      The analysis of HDA in urine is a useful technique for assessing exposure to
      isocyanates in paint sprayers. The simplicity of this approach has allowed wide
      scale use of biological monitoring in an industry dominated by small and micro
      businesses. Biological monitoring of exposure has enabled individual companies,
      and sprayers, to check that their control measures are working. This study showed
      overall lower levels of HDA in paint sprayers following SHADs. These lower levels
      have been maintained across a wider population of UK paint sprayers over the
      succeeding years. Whilst there may be many reasons for the reduction in exposure,
      the weight of evidence suggests that the key messages about exposure control
      measures, delivered through the SHADs and other means, were influential.

PMID- 22986426
TI  - Aggregation of exposure level and probability into a single metric in job
      exposure matrices creates bias.
AB  - Job-exposure matrices (JEMs) are often used in occupational epidemiological
      studies to provide an exposure estimate for a typical person in a 'job' during a
      particular time period. A JEM can produce exposure estimates on a variety of
      scales, such as (but not limited to) binary assessments of presence or absence of
      exposure, ordinal ranking of exposure level and frequency, and quantitative
      exposure estimates of exposure intensity and frequency. Specifically, one popular
      approach to construct a JEM, engendered in a Finnish job exposure matrix
      (FINJEM), provides a probability that a worker within an occupational group is
      exposed and an estimate of intensity of exposure among the exposed workers within
      this occupation. Often the product of the probability and intensity (aka level)
      is used to obtain the estimate of exposure for the epidemiological analyses. This
      procedure aggregates exposure across exposed and non-exposed individuals and the
      effect of this particular procedure on epidemiological analyses has never been
      studied. We developed a theoretical framework for understanding how these
      aggregate exposure estimates relate to true exposure (either unexposed or log
      normally distributed for 'exposed'), assuming that there is no uncertainty about
      estimates of level and probability of exposure. Theoretical derivations show that
      multiplying occupation-specific exposure level and probability of non-zero
      exposure results in both systematic and differential measurement errors.
      Simulations demonstrated that under certain conditions bias in odds ratios in a
      cohort study away from the null are possible and that this bias is smaller when
      (a) arithmetic rather than geometric mean is used to assess exposure level and
      (b) exposure level and prevalence are positively correlated. We illustrate the
      potential impact of using the specified JEM in a simulation based on a case
      control study of non-Hodgkin lymphoma and exposure to ionizing and non-ionizing
      radiation. Inflation of standard errors in the log-odds was observed as well as
      bias away from null for two out of three specific exposures/data structures.
      Overall, it is clear that influence of the phenomenon we studied on
      epidemiological results is complex and difficult to predict, being influenced a
      great deal by the structure of data. We recommend exploring the influence of JEMs
      that use the product of exposure level and probability in epidemiological
      analyses through simulations during planning of such studies to assess both the
      expected extent of the potential bias in risk estimates and impact on power. The
      SAS and R code required to implement such simulations are provided. All our
      calculations are either theoretical or based on simulated data.

PMID- 22986427
TI  - Associations between the occupational stress index and hypertension, type 2
      diabetes mellitus, and lipid disorders in middle-aged men and women.
AB  - INTRODUCTION: Retrospective and prospective studies show that stress at work is
      linked to an increased risk of hypertension, diabetes mellitus, and coronary
      heart disease. However, the nature of the contributory job stressors and
      biological mechanisms need further elucidation. OBJECTIVES: The study is aimed to
      determine the associations between aspects of the occupational stress index (OSI)
      and arterial hypertension, diabetes mellitus (DM) type 2, and lipid disorders in
      working middle-aged men and women. METHODS: The cross-sectional study involved
      989 middle-aged men and women in different occupations. The OSI was calculated by
      using standardized questionnaires. The total participation rate was 93%.
      Occupational stressors were divided into seven groups: High Demands, Strictness,
      Underload, Extrinsic Time Pressure, Noxious Exposure, Avoidance, and
      Conflict/Uncertainty. Serum lipid levels, glucoregulation, blood pressure, and
      cardiovascular risk factors were measured. RESULTS: For both women and men, the
      total OSI score associated significantly with DM (women: odds ratio [OR] 2.4, 95%
      confidence intervals [CI] 1.67-3.45; men: 1.21, 1.15-1.45), any type of
      dyslipidemia (women: 1.54, 1.17-2.03; men: 1.31, 1.24-1.39), and arterial
      hypertension (women: 1.15, 1.10-1.21; men: 1.58, 1.49-1.68). The group as a whole
      showed associations between total OSI and low high-density lipoprotein (HDL)
      cholesterol, high total cholesterol, and high triglyceride levels. Of the OSI
      aspects, Underload associated significantly in both men and women with arterial
      hypertension (women: 3.48, 1.91-6.31; men: 2.71, 1.96-3.75) and dyslipidemia
      (women: 3.26, 2.13-4.99; men: 2.11, 1.76-2.52). Underload was also associated
      with several lipid abnormalities in the group as a whole. It associated with DM
      in women only (4.7, 2.84-7.81). All remaining OSI aspects also associated
      significantly and positively with DM in women only. Conversely, in male workers,
      but not female workers, High Demand, Conflict/Uncertainty, and Extrinsic Time
      Pressure associated significantly with arterial hypertension. Strictness and
      Conflict/Uncertainty associated positively with dyslipidemia in women only.
      Noxious Exposures associated positively with DM and arterial hypertension in
      women only. CONCLUSIONS: The study provides evidence for the association of work
      stress with metabolic disorders and hypertension. Total OSI associated
      significantly with DM type 2, arterial hypertension, and dyslipidemia in both
      genders. Different OSI aspects associated with these health issues in gender- and
      occupational-specific patterns. Underload, which represents lack of social
      communication, simple task preparation, and underestimation of working results,
      associated most strongly of all OSI aspects with disease in both the sexes.

PMID- 22986428
TI  - Spine surgery--approach size does matter.

PMID- 22986432
TI  - Stroke: sun exposure and vitamin D linked to the risk of stroke.

PMID- 22986430
TI  - Sepsis-associated encephalopathy.
AB  - Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs
      secondary to infection in the body without overt CNS infection. SAE is frequently
      encountered in critically ill patients in intensive care units, and in up to 70%
      of patients with severe systemic infection. The severity of SAE can range from
      mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial
      nerves are almost always spared, but most severe cases have an associated
      critical illness neuromyopathy. Development of SAE probably involves a number of
      mechanisms that are not mutually exclusive and vary from patient to patient.
      Substantial neurological and psychological morbidities often occur in survivors.
      Mortality is almost always due to multiorgan failure rather than neurological
      complications, and is almost 70% in patients with severe SAE. Further research
      into the pathophysiology, management and prevention of SAE is needed. This Review
      discusses the epidemiology and clinical presentation of SAE. Recent evidence for
      SAE pathophysiology is outlined and a diagnostic approach to patients with this
      syndrome is presented. Lastly, prognosis and management of SAE is discussed.

PMID- 22986433
TI  - Neuro-oncology: understanding the molecular complexity of medulloblastoma.

PMID- 22986434
TI  - Stroke: New mechanical clot retrieval devices show superiority in patients with
      acute ischaemic stroke.

PMID- 22986429
TI  - Neuroplasticity and functional recovery in multiple sclerosis.
AB  - The development of therapeutic strategies that promote functional recovery is a
      major goal of multiple sclerosis (MS) research. Neuroscientific and
      methodological advances have improved our understanding of the brain's recovery
      from damage, generating novel hypotheses about potential targets and modes of
      intervention, and laying the foundation for development of scientifically
      informed recovery-promoting strategies in interventional studies. This Review
      aims to encourage the transition from characterization of recovery mechanisms to
      development of strategies that promote recovery in MS. We discuss current
      evidence for functional reorganization that underlies recovery and its
      implications for development of new recovery-oriented strategies in MS. Promotion
      of functional recovery requires an improved understanding of recovery mechanisms
      that can be modulated by interventions and the development of robust measurements
      of therapeutic effects. As imaging methods can be used to measure functional and
      structural alterations associated with recovery, this Review discusses their use
      to obtain reliable markers of the effects of interventions.

PMID- 22986435
TI  - Disease mechanisms in MS: the potassium channel KIR4.1--a potential autoantigen
      in MS.
AB  - Multiple sclerosis is an inflammatory, demyelinating disease in which antigens of
      the myelin sheath have been considered the autoimmune target. A recent study
      suggests that the potassium channel KIR4.1 is another potential autoantigen in
      some patients with multiple sclerosis, and might also be a target in other
      demyelinating diseases.

PMID- 22986436
TI  - Cerebrovascular malformations: seizure risk with AVMs--medical vs interventional
      management.

PMID- 22986437
TI  - Linaclotide for irritable bowel syndrome with constipation: a 26-week,
      randomized, double-blind, placebo-controlled trial to evaluate efficacy and
      safety.
AB  - OBJECTIVES: Linaclotide is a minimally absorbed peptide guanylate cyclase-C
      agonist. The objective of this trial was to determine the efficacy and safety of
      linaclotide treatment in patients with irritable bowel syndrome with constipation
      (IBS-C) over 26 weeks. METHODS: This phase 3, double-blind, parallel-group,
      placebo-controlled trial randomized IBS-C patients to placebo or 290 MUg of oral
      linaclotide once daily for a 26-week treatment period. The primary and the
      secondary efficacy assessments were evaluated over the first 12 weeks of
      treatment. Primary end points included the Food and Drug Administration's (FDA's)
      end point for IBS-C (responder: a patient who reported (i) improvement of >= 30 %
      from baseline in average daily worst abdominal pain score and (ii) increase of >=
      1 complete spontaneous bowel movement (CSBM) from baseline, both in the same week
      for >= 6 / 12 weeks) and three other primary end points, based on improvements in
      abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored.
      RESULTS: In all, 804 patients (mean age = 44 years, female = 90 % , white = 78 %
      ) were evaluated; 33.7 % of linaclotide-treated patients were FDA end point
      responders, vs. 13.9 % of placebo-treated patients ( P < 0.0001) (number needed
      to treat = 5.1, 95 % confidence interval (CI): 3.9, 7.1). The pain responder
      criterion of the FDA end point was met by 48.9 % of linaclotide-treated patients
      vs. 34.5 % of placebo-treated patients (number needed to treat = 7.0, 95 % CI:
      4.7, 13.1), and the CSBM responder criterion was met by 47.6 % of linaclotide
      treated patients, vs. 22.6 % of placebo patients (number needed to treat = 4.0,
      95 % CI: 3.2, 5.4). Remaining primary end points ( P < 0.0001) and all secondary
      end points ( P < 0.001), including abdominal pain, abdominal bloating, and bowel
      symptoms (SBM and CSBM rates, Bristol Stool Form Scale (BSFS) score, and
      straining), were also statistically significantly improved with linaclotide vs.
      placebo. Statistically significant differences from placebo were observed for
      responder and continuous end points over 26 weeks of treatment. AE incidence was
      similar between treatment groups, except for diarrhea, which caused
      discontinuation in 4.5 % of linaclotide patients vs. 0.2 % of placebo patients.
      CONCLUSIONS: Linaclotide 290 MUg once daily significantly improved abdominal and
      bowel symptoms associated with IBS-C over 26 weeks of treatment.

PMID- 22986438
TI  - Quantitative profiling of gut microbiota of children with diarrhea-predominant
      irritable bowel syndrome.
AB  - OBJECTIVES: Human intestinal microbiota has a number of important roles in human
      health and is also implicated in several gastrointestinal disorders. The goal of
      this study was to determine the gut microbiota in two groups of pre- and
      adolescent children: healthy volunteers and children diagnosed with diarrhea
      predominant irritable bowel syndrome (IBS-D). METHODS: Phylogenetic Microbiota
      Array was used to obtain quantitative measurements of bacterial presence and
      abundance in subjects ' fecal samples. We utilized high-throughput DNA
      sequencing, quantitative PCR, and fluorescent in situ hybridization to confirm
      microarray findings. RESULTS: Both sample groups were dominated by the phyla
      Firmicutes, Bacteroidetes, and Actinobacteria, which cumulatively constituted 91
      % of overall sample composition on average. A core microbiome shared among
      analyzed samples encompassed 55 bacterial phylotypes dominated by genus
      Ruminococcus ; members of genera Clostridium , Faecalibacterium, Roseburia,
      Streptococcus , and Bacteroides were also present. Several genera were found to
      be differentially abundant in the gut of healthy and IBS groups: levels of
      Veillonella , Prevotella , Lactobacillus , and Parasporo bacterium were increased
      in children diagnosed with IBS, whereas members of Bifidobacterium and
      Verrucomicrobium were less abundant in those individuals. By calculating a
      nonparametric correlation matrix among abundances of different genera in all
      samples, we also examined potential associations among intestinal microbes.
      Strong positive correlations were found between abundances of Veillonella and
      both Haemophilus and Streptococcus , between Anaerovorax and Verrucomicrobium ,
      and between Tannerella and Anaerophaga . CONCLUSIONS: Although at the higher
      taxonomical level gut microbiota was similar between healthy and IBS-D children,
      specific differences in the abundances of several bacterial genera were revealed.
      Core microbiome in children was dominated by Clostridia. Putative relationships
      identified among microbial genera provide testable hypotheses of cross-species
      associations among members of human gut microbiota

PMID- 22986439
TI  - Normal values for high-resolution anorectal manometry in healthy women: effects
      of age and significance of rectoanal gradient.
AB  - OBJECTIVES: High-resolution manometry (HRM) is used to measure anal pressures in
      clinical practice but normal values have not been available. Although rectal
      evacuation is assessed by the rectoanal gradient during simulated evacuation,
      there is substantial overlap between healthy people and defecatory disorders, and
      the effects of age are unknown. We evaluated the effects of age on anorectal
      pressures and rectal balloon expulsion in healthy women. METHODS: Anorectal
      pressures (HRM), rectal sensation, and balloon expulsion time (BET) were
      evaluated in 62 asymptomatic women ranging in age from 21 to 80 years (median age
      44 years) without risk factors for anorectal trauma. In total, 30 women were aged
      <50 years. RESULTS: Age is associated with lower (r=-0.47, P<0.01) anal resting
      (63 (5) (>=50 years), 88 (3) (<50 years), mean (s.e.m.)) but not squeeze
      pressures; higher rectal pressure and rectoanal gradient during simulated
      evacuation (r=0.3, P<0.05); and a shorter (r=-0.4, P<0.01) rectal BET (17 (9) s
      (>=50 years) vs. 31 (10) s (<50 years)). Only 5 women had a prolonged (>60 s)
      rectal BET but 52 had higher anal than rectal pressures (i.e., negative gradient)
      during simulated evacuation. The gradient was more negative in younger (-41 (6)
      mm Hg) than older (-12 (6) mm Hg) women and negatively (r=-0.51, P<0.0001)
      correlated with rectal BET but only explained 16% of the variation in rectal BET.
      CONCLUSIONS: These observations provide normal values for anorectal pressures by
      HRM. Increasing age is associated with lower anal resting pressure, a more
      positive rectoanal gradient during simulated evacuation, and a shorter BET in
      asymptomatic women. Although the rectoanal gradient is negatively correlated with
      rectal BET, this gradient is negative even in a majority of asymptomatic women,
      undermining the utility of a negative gradient for diagnosing defecatory
      disorders by HRM.

PMID- 22986440
TI  - A 12-week, randomized, controlled trial with a 4-week randomized withdrawal
      period to evaluate the efficacy and safety of linaclotide in irritable bowel
      syndrome with constipation.
AB  - OBJECTIVES: Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The
      objective of this trial was to determine the efficacy and safety of linaclotide
      in patients with irritable bowel syndrome with constipation (IBS-C). METHODS:
      This phase 3, double-blind, parallel-group, placebo-controlled trial randomized
      IBS-C patients to placebo or 290 MU g oral linaclotide once daily in a 12-week
      treatment period, followed by a 4-week randomized withdrawal (RW) period. There
      were four primary end points, the Food and Drug Administration ' s (FDA ' s)
      primary end point for IBS-C (responder: improvement of >= 30 % in average daily
      worst abdominal pain score and increase by >= 1 complete spontaneous bowel
      movement (CSBM) from baseline (same week) for at least 50 % of weeks assessed)
      and three other primary end points, based on improvements in abdominal pain and
      CSBMs for 9 / 12 weeks. Adverse events (AEs) were monitored. RESULTS: The trial
      evaluated 800 patients (mean age = 43.5 years, female = 90.5 % , white = 76.9 %
      ). The FDA end point was met by 136 / 405 linaclotide-treated patients (33.6 % ),
      compared with 83 / 395 placebo-treated patients (21.0 % ) ( P < 0.0001) (number
      needed to treat: 8.0, 95 % confidence interval: 5.4, 15.5). A greater percentage
      of linaclotide patients, compared with placebo patients, reported for at least 6
      / 12 treatment period weeks, a reduction of >= 30 % in abdominal pain (50.1 vs.
      37.5 % , P = 0.0003) and an increase of >= 1 CSBM from baseline (48.6 vs. 29.6 %
      , P < 0.0001). A greater percentage of linaclotide patients vs. placebo patients
      were also responders for the other three primary end points ( P < 0.05).
      Significantly greater improvements were seen in linaclotide vs. placebo patients
      for all secondary end points ( P < 0.001). During the RW period, patients
      remaining on linaclotide showed sustained improvement; patients re-randomized
      from linaclotide to placebo showed return of symptoms, but without worsening of
      symptoms relative to baseline. Diarrhea, the most common AE, resulted in
      discontinuation of 5.7 % of linaclotide and 0.3 % of placebo patients.
      CONCLUSIONS: Linaclotide significantly improved abdominal pain and bowel symptoms
      associated with IBS-C for at least 12 weeks; there was no worsening of symptoms
      compared with baseline following cessation of linaclotide during the RW period.

PMID- 22986441
TI  - Intracoronary GP IIb/IIIa inhibitors: could eptifibatide be the new kid on the
      block?

PMID- 22986443
TI  - Retraction. Use of multiple biomarkers for the localization and characterization
      of colon cancer stem cells by indirect immunocytochemistry.
AB  - An international independent review was conducted on the above article by the
      editor following a complaint. The expert reviewers agreed that the interpretation
      of the results was not correct. The article is retracted as the results were not
      adequately proven. [the original article was published in the International
      Journal of Oncology 41: 285-291, 2012 DOI: 10.3892/ijo.2012.1430].

PMID- 22986442
TI  - Hyperglycemia-induced stimulation of glucose transport in skeletal muscle
      measured by PET-[18F]6FDG and [18F]2FDG.
AB  - A physiologically based model proposed by our group has been developed to assess
      glucose transport and phosphorylation in skeletal muscle. In this study, we
      investigated whether our model has the ability to detect a glucose-induced
      increase in glucose transport in skeletal muscle. In particular, we used small
      animal positron emission tomography (PET) data obtained from [18F]6-fluoro-6
      deoxy-D-glucose ([18F]6FDG). A 2 h PET scan was acquired following a bolus
      injection of [18F]6FDG in rats currently under euglycemic or hyperglycemic
      conditions, while somatostatin was infused during both conditions in order to
      prevent a rise in the endogenous plasma insulin concentration. We were thus able
      to assess the effect of hyperglycemia per se. For a comparison of
      radiopharmaceuticals, additional rats were studied under the same conditions,
      using [18F]2-fluoro-2-deoxy-D-glucose ([18F]2FDG). When [18F]6FDG was used, the
      time-activity curves (TACs) for skeletal muscle had distinctly different shapes
      during euglycemic and hyperglycemic conditions. This was not the case with
      [18F]2FDG. For both [18F]6FDG and [18F]2FDG, the model detects increases in both
      interstitial and intracellular glucose concentrations, increases in the maximal
      velocity of glucose transport and increases in the rate of glucose transport, all
      in response to hyperglycemia. In contrast, there was no increase in the maximum
      velocity of glucose phosphorylation or in the glucose phosphorylation rate. Our
      model-based analyses of the PET data, obtained with either [18F]6FDG or
      [18F]2FDG, detect physiological changes consistent with established behavior.
      Moreover, based on differences in the TAC shapes, [18F]6FDG appears to be
      superior to [18F]2FDG for evaluating the effect of hyperglycemia on glucose
      metabolism in skeletal muscle.

PMID- 22986444
TI  - Abstracts of the 9th Annual ENETS (European Neuroendocrine Tumor Society)
      Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease. March
      7-9, 2012, Copenhagen, Denmark.

PMID- 22986445
TI  - Effect of high-speed treadmill training with a body weight support system in a
      sport acceleration program with female soccer players.
AB  - Maximum running speed and acceleration are essential components in many sports.
      The identification of specific training protocols to maximize sprint speed would
      be useful knowledge for coaches and players. The purpose of this study was to
      determine the effect of a high-speed treadmill (HST) with the use of a body
      weight support (BWS) system in a 6-week sport acceleration program (SAP) on
      female soccer athlete's 40-yard sprint time and maximal isometric knee flexor and
      extensor strength. Two treatment groups and one control group were created. Both
      treatment groups participated in a 12-session SAP. The first treatment group (n =
      12) used a BWS system while running on a HST; the second group (n = 12) used a
      standard treadmill (ST) with no BWS system. The participants of the control group
      (n = 8), NT, did not participate in a sports acceleration program and did not
      alter their exercise routines outside of the study. An analysis of covariance was
      performed using baseline measures as the covariate. The 40-yard sprint times for
      both treatment groups were shown to improve significantly compared with the
      control group (p < 0.001). Isometric knee flexor strength showed a greater
      increase in the ST group (p = 0.026) than in the other 2 groups, whereas knee
      extensor strengths did not show significant differences between treatment groups
      and control group (p > 0.05). Participants in the ST group had a much higher rate
      (66%) of shin splints and foot pain throughout the study than those in the HST
      (8%) and NT (0%) groups. These results can help high school coaches and athletes
      determine the optimal treadmill training regime.

PMID- 22986446
TI  - Brain D-amino acids: a novel class of neuromodulators.

PMID- 22986447
TI  - Phosphine-alkene ligand-mediated alkyl-alkyl and alkyl-halide elimination
      processes from palladium(II).
AB  - N-Diphenylphosphino-7-aza-benzobicyclo[2.2.1]hept-2-ene (2) behaves as a
      chelating phosphine-alkene ligand for Pd(0) and Pd(II), promoting direct alkyl
      alkyl and indirect alkyl-halide reductive elimination reactions due to the
      stabilisation of the resulting bis(phosphine-alkene)Pd(0) complex.

PMID- 22986448
TI  - Current application of neurochemical biomarkers in the prediction and
      differential diagnosis of Alzheimer's disease and other neurodegenerative
      dementias.
AB  - In light of the dramatically increasing prevalence of Alzheimer's disease (AD) to
      be expected in the future, the development of novel therapeutics, improved
      differential and early diagnostics, and means for the identification of
      individuals at risk are urgently needed. At present, instruments for a reliable
      differential diagnosis in clinical dementia, mild cognitive impairment, or
      prodromal stages have direct practical implications for differentiating secondary
      dementias from neurodegenerative conditions and for treatment decisions. It may
      also be reasonable to enforce the incorporation of biomarkers into clinical
      studies as surrogate outcome parameters and as an attempt to optimize recruitment
      criteria. Recently, revised research criteria increasingly rely on the
      interpretation of biomarker patterns, including neuroimaging and CSF-based
      neurochemical dementia diagnosis (NDD) in supporting the clinical diagnosis.
      Here, we review the performance of current core CSF biomarkers (Abeta(42)
      peptide, total tau protein and phosphorylated tau species) and try to define
      objectives for prospective markers, also considering blood-based tests, which
      would increase the acceptance and wide application of NDD. Moreover, we evaluate
      the role and the limitations of genotyping in the predictive diagnosis of AD.

PMID- 22986449
TI  - Magnetic resonance spectroscopy study of the glutamatergic system in adolescent
      males with high-functioning autistic disorder: a pilot study at 4T.
AB  - The pilot study aimed at examining the neural glutamatergic activity in autism.
      Seven adolescent males (mean age: 14 +/- 1.8; age range: 12-17 years) with intact
      intellectual capacity (mean IQ: 108 +/- 14.26; IQ range: 85-127) suffering from
      autistic disorder and an equal number of age- and sex-matched healthy controls
      underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results
      indicated significantly high glutamate (Glu) levels in the anterior cingulate
      cortex of autistic disorder versus control subjects (paired t test p = 0.01) and
      a trend for lower Glu in the right medial temporal lobe, which was not
      statistically different between the groups (paired t test p = 0.06). These
      preliminary findings support the glutamatergic dysregulation hypothesis in autism
      and need to be replicated in a larger sample.

PMID- 22986451
TI  - Impact of delirium on the course of Alzheimer disease.
AB  - BACKGROUND: Delirium is characterized by acute cognitive impairment. We examined
      the association of delirium with long-term cognitive trajectories in older adults
      with Alzheimer disease (AD). METHODS: We evaluated prospectively collected data
      from a nested cohort of hospitalized patients with AD (n = 263) in the
      Massachusetts Alzheimer Disease Research Center patient registry between January
      1, 1991, and June 30, 2006 (median follow-up duration, 3.2 years). Cognitive
      function was measured using the information-memory-concentration (IMC) section of
      the Blessed Dementia Rating Scale. Delirium was identified using a validated
      medical record review method. The rate of cognitive deterioration was contrasted
      using random-effects regression models. RESULTS: Fifty-six percent of patients
      with AD developed delirium during hospitalization. The rate of cognitive
      deterioration before hospitalization did not differ significantly between
      patients who developed delirium (1.4 [95% CI, 0.7-2.1] IMC points per year) and
      patients who did not develop delirium (0.8 [95% CI, 0.3-1.3] IMC points per year)
      (P = .24). After adjusting for dementia severity, comorbidity, and demographic
      characteristics, patients who had developed delirium experienced greater
      cognitive deterioration in the year following hospitalization (3.1 [95% CI, 2.1
      4.1] IMC points per year) relative to patients who had not developed delirium
      (1.4 [95% CI, 0.2-2.6] IMC points per year). The ratio of these changes suggests
      that cognitive deterioration following delirium proceeds at twice the rate in the
      year after hospitalization compared with patients who did not develop delirium.
      Patients who had developed delirium maintained a more rapid rate of cognitive
      deterioration throughout a 5-year period following hospitalization. Sensitivity
      analyses that excluded rehospitalized patients and included matching on baseline
      cognitive function and baseline rate of cognitive deterioration produced
      essentially identical results. CONCLUSIONS: Delirium is highly prevalent among
      persons with AD who are hospitalized and is associated with an increased rate of
      cognitive deterioration that is maintained for up to 5 years. Strategies to
      prevent delirium may represent a promising avenue to explore for ameliorating
      cognitive deterioration in AD.

PMID- 22986450
TI  - Francisella tularensis alters human neutrophil gene expression: insights into the
      molecular basis of delayed neutrophil apoptosis.
AB  - We demonstrated recently that Francisella tularensis profoundly impairs human
      neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used
      human oligonucleotide microarrays to test the hypothesis that changes in
      neutrophil gene expression contribute to this phenotype, and now demonstrate that
      F. tularensis live vaccine strain (LVS) caused significant changes in neutrophil
      gene expression over a 24-hour time period relative to the uninfected controls.
      Of approximately 47,000 genes analyzed, 3,435 were significantly up- or
      downregulated by LVS, including 365 unique genes associated with apoptosis and
      cell survival. Specific targets in this category included genes asso-ciated with
      the intrinsic and extrinsic apoptotic pathways (CFLAR, TNFAIP3, TNFRSF10D, SOD2,
      BCL2A1, BIRC4, PIM2, TNFSF10, TNFRSF10C, CASP2 and CASP8) and genes that act via
      the NFKB pathway and other mechanisms to prolong cell viability (NFKB1, NFKB2 and
      RELA, IL1B, CAST, CDK2,GADD45B, BCL3, BIRC3, CDK2, IL1A, PBEF1, IL6, CXCL1, CCL4
      and VEGF). The microarray data were confirmed by qPCR and pathway analysis.
      Moreover, we demonstrate that the X-linked inhibitor of apoptosis protein
      remained abundant in polymorphonuclear leukocytes over 48 h of LVS infection,
      whereas BAX mRNA and protein were progressively downregulated. These data
      strongly suggest that antiapoptotic and prosurvival mechanisms collaborate to
      sustain the viability of F. tularensis--infected neutrophils.

PMID- 22986452
TI  - Pretreatment neutrophil to lymphocyte ratio is associated with response to
      therapy and prognosis of advanced non-small cell lung cancer patients treated
      with first-line platinum-based chemotherapy.
AB  - BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been shown to be a prognosis
      indicator in different types of cancer. We aimed to investigate the association
      between NLR and therapy response, progression free survival (PFS) and overall
      survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated
      with first-line platinum-based chemotherapy. METHODS: Patients who were
      hospitalized between January 2007 and December 2010 were enrolled and eliminated
      according to the inclusion and exclusion criteria. The NLR was defined as the
      absolute neutrophil count divided by the absolute lymphocyte count. Logistic
      regression analysis was applied for response rate and Cox regression analysis was
      adopted for PFS and OS. A P value of <=0.05 was considered to be statistically
      significant. RESULTS: A total of 182 patients were enrolled in the current study.
      The median PFS was 164.5 days and median OS was 439.5 days. The statistical
      analysis data indicated that low pretreatment NLR (<= 2.63) (OR = 2.043, P =
      0.043), decreased posttreatment NLR (OR = 2.368, P = 0.013), well and moderate
      differentiation (OR = 2.773, P = 0.021) and normal CEA level (<= 9.6 ng/ml) (OR =
      2.090, P = 0.046) were associated with response to first-line platinum-based
      chemotherapy. A high pretreatment NLR (HR = 1.807, P = 0.018 for PFS, HR = 1.761,
      P = 0.020 for OS) and distant metastasis (HR = 2.118, P = 0.008 for PFS, HR =
      2.753, P = 0.000 for OS) were independent prognostic factors for PFS and OS.
      CONCLUSION: Elevated pretreatment NLR might be a potential biomarker of worse
      response to first-line platinum-based chemotherapy and shorter PFS and OS for
      advanced NSCLC patients. To confirm these findings, larger, prospective and
      randomized studies are needed.

PMID- 22986453
TI  - Up-regulation of Foxp3 participates in progression of cervical cancer.
AB  - Foxp3 was identified as a key protein in mediating inhibitory functions of
      regulatory T cell (Treg). Foxp3 was thought to express only in the T cell lineage
      until recently when some researches reported that Foxp3 was also expressed by
      cancer cells. In this study, we describe for the first time the expression of
      Foxp3 in cervical cancer. Progression from cervical intraepithelial neoplasia
      (CIN) to cervical cancer is a multistep process initiated by persistent infection
      with high-risk human papillomavirus (HPV). P16(INK4a) is a crucial marker of HPV
      integration into host cells. In the present study, expressions of Foxp3 and
      P16(INK4a) in CIN and cervical cancer were detected by immunohistochemistry. Our
      results found expression level of Foxp3 was increased during the progression of
      cervical neoplasia. Moreover, up-regulation of Foxp3 appeared to be correlated
      with the expression of P16(INK4a). Examination of the role of Foxp3 in
      differentiation by double immunostaining for cytokeratin 10 (CK10) showed
      significant association between Foxp3 expression and differentiation (Foxp3 vs
      CK10). Furthermore, positive expression of Foxp3 was correlated with tumor size.
      These data suggest that Foxp3 may play an important role in differentiation and
      growth of cervical cancer cells. Our findings provide new insights regarding the
      role of Foxp3 in differentiation and its association with HPV infection during
      the development of cervical cancer.

PMID- 22986454
TI  - The development of standard samples with a defined number of antigen-specific T
      cells to harmonize T cell assays: a proof-of-principle study.
AB  - The validation of assays that quantify antigen-specific T cell responses is
      critically dependent on cell samples that contain clearly defined measurable
      numbers of antigen-specific T cells. An important requirement is that such cell
      samples are handled and analyzed in a comparable fashion to peripheral blood
      mononuclear cells (PBMC). We performed a proof-of-principle study to show that
      retrovirally TCR-transduced T cells spiked at defined numbers in autologous PBMC
      can be used as standard samples for HLA/peptide multimer staining. NY-ESO-1157
      165-specific, TCR-transduced CD8+ T cell batches were successfully generated from
      PBMC of several HLA-A*0201 healthy donors, purified by magnetic cell sorting on
      the basis of HLA tetramer (TM) staining and expanded with specific antigen in
      vitro. When subsequently spiked into autologous PBMC, the detection of these
      CD3+CD8+TM+ T cells was highly accurate with a mean accuracy of 91.6 %. The
      standard cells can be preserved for a substantial period of time in liquid
      nitrogen. Furthermore, TM staining of fresh and cryopreserved standard samples
      diluted at decreasing concentrations into autologous cryopreserved unspiked PBMC
      revealed that the spiked CD3+CD8+TM+ T cells could be accurately detected at all
      dilutions in a linear fashion with a goodness-of-fit of over 0.99 at a frequency
      of at least 0.02 % among the CD3+CD8+ T cell population. Notably, the CD3+CD8+TM+
      cells of the standard samples were located exactly within the gates used to
      analyze patient samples and displayed a similar scatter pattern. The performance
      of the cryopreserved standard samples in the hands of 5 external investigators
      was good with an inter-laboratory variation of 32.9 % and the doubtless
      identification of one outlier.

PMID- 22986456
TI  - Decreased serum chemerin levels in male Japanese patients with type 2 diabetes:
      sex dimorphism.
AB  - Chemerin, a recently discovered adipocytokine plays an important role in obesity
      and obesity-associated metabolic complications.  However, the role of chemerin in
      the pathogenesis of type 2 diabetes mellitus (T2DM) has not fully been
      elucidated.  We compared the serum chemerin levels and metabolic parameters
      between 88 control subjects, 86 patients with metabolic syndrome (MS), and 147
      patients with T2DM in a Japanese population and further analyzed their
      correlation.  Enzyme-linked immunosorbent assay was used to measure the serum
      chemerin levels.  The chemerin levels were significantly higher in male than in
      female control subjects (p < 0.005), with significant decreases in patients with
      T2DM compared with those with MS and control subjects (164.9 +/- 6.3 ng/mL vs.
      209.8 +/- 7.7 and 218.7 +/- 7.3 ng/mL; p < 0.0001 vs. p < 0.0001, respectively)
      but no significant differences in female subjects.  The multiple regression
      analysis revealed that the chemerin levels negatively correlated with the fasting
      glucose and HbA1c levels in total and male subjects.  In the patients with T2DM,
      the chemerin levels negatively correlated with fasting glucose and high-density
      lipoprotein cholesterol but positively correlated with body mass index (BMI), and
      total cholesterol and triglyceride levels.  The negative correlation between the
      chemerin and fasting glucose levels remained significant after adjustment for
      age, sex, and BMI in the total and male subjects and those with T2DM.  These
      results suggest the role of chemerin in sex dimorphism and a potential link
      between chemerin levels and T2DM pathogenesis in a Japanese population.

PMID- 22986457
TI  - Kinetics of degradation of sulfur mustard and sarin simulants on HKUST-1 metal
      organic framework.
AB  - The applicability of HKUST-1 for the degradation of sulfur mustard and sarin
      simulants was studied with and without coadsorbed water. Degradation was found to
      be via hydrolysis and dependent on the nucleophilic substitution reaction, vapour
      pressure and molecular diameter of the toxicants.

PMID- 22986459
TI  - Regenerative medicine: Adipose stem cells fail to boost cartilage repair in rats.

PMID- 22986458
TI  - Paediatric rheumatic disease: Classification warfare.
AB  - In the absence of definitive diagnostic tests, several schemes for the
      classification of paediatric vasculitis have been devised and periodically
      updated, but are these revisions necessary and useful?

PMID- 22986455
TI  - Bioinformatics for cancer immunology and immunotherapy.
AB  - Recent mechanistic insights obtained from preclinical studies and the approval of
      the first immunotherapies has motivated increasing number of academic
      investigators and pharmaceutical/biotech companies to further elucidate the role
      of immunity in tumor pathogenesis and to reconsider the role of immunotherapy.
      Additionally, technological advances (e.g., next-generation sequencing) are
      providing unprecedented opportunities to draw a comprehensive picture of the
      tumor genomics landscape and ultimately enable individualized treatment. However,
      the increasing complexity of the generated data and the plethora of
      bioinformatics methods and tools pose considerable challenges to both tumor
      immunologists and clinical oncologists. In this review, we describe current
      concepts and future challenges for the management and analysis of data for cancer
      immunology and immunotherapy. We first highlight publicly available databases
      with specific focus on cancer immunology including databases for somatic
      mutations and epitope databases. We then give an overview of the bioinformatics
      methods for the analysis of next-generation sequencing data (whole-genome and
      exome sequencing), epitope prediction tools as well as methods for integrative
      data analysis and network modeling. Mathematical models are powerful tools that
      can predict and explain important patterns in the genetic and clinical
      progression of cancer. Therefore, a survey of mathematical models for tumor
      evolution and tumor-immune cell interaction is included. Finally, we discuss
      future challenges for individualized immunotherapy and suggest how a combined
      computational/experimental approaches can lead to new insights into the molecular
      mechanisms of cancer, improved diagnosis, and prognosis of the disease and
      pinpoint novel therapeutic targets.

PMID- 22986460
TI  - Bone: New guidelines for multistep fracture prevention in men.
AB  - Study of the efficacy of fracture prevention approaches has been neglected in
      men, in comparison with women. Guidelines from the Endocrine Society for the
      management of osteoporosis and fracture risk in men are thus welcome, but further
      research into fracture prevention in men is required.

PMID- 22986461
TI  - Rheumatoid arthritis: RF levels predict RA risk in the general population.

PMID- 22986463
TI  - Altered microstructure of white matter except the corpus callosum is independent
      of prematurity.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) reflects the maturation of the brain
      microstructure. Although preterm infants are at significant risk for altered
      brain microstructure, it remains unclear whether this is affected by prematurity
      itself or other clinical factors. OBJECTIVES: To investigate DTI parameters in
      preterm infants at a term-equivalent age (TEA) compared with healthy term infants
      and to assess the associations between DTI parameters and clinical factors that
      may affect brain development. METHODS: We studied 34 preterm infants without
      apparent brain lesions and 12 healthy term infants using tract-based spatial
      statistics. Region-of-interest analysis was performed in the posterior and
      anterior limbs of the internal capsule (PLIC and ALIC), corpus callosum (CC),
      optic radiation, and cerebral peduncle. RESULTS: Preterm infants had
      significantly decreased fractional anisotropy (FA) in nearly the entire white
      matter (WM) compared with term infants (p < 0.01). Multiple regression analysis
      showed that FA in the PLIC, ALIC, optic radiation, and cerebral peduncle were
      positively associated with postmenstrual age (PMA) at imaging and that the
      apparent diffusion coefficient was negatively associated with PMA. Only FA in the
      CC was positively correlated with gestational age. Chronic lung disease (CLD) and
      postnatal infection were associated with decreased FA in the CC and PLIC,
      respectively. CONCLUSIONS: Preterm infants at TEA showed an altered
      microstructure of the WM compared with healthy term infants. The altered
      microstructure of the measured WM except the CC was independent of the degree of
      prematurity. Chronic lung disease and postnatal infection are related to
      localized WM alterations.

PMID- 22986464
TI  - O6-Methylguanine-DNA methyltransferase is a novel negative effector of invasion
      in glioblastoma multiforme.
AB  - The dismal prognosis of glioblastoma multiforme (GBM) is mostly due to the high
      propensity of GBM tumor cells to invade. We reported an inverse relationship
      between GBM angiogenicity and expression of the DNA repair protein O(6)
      methylguanine-DNA methyltransferase (MGMT), which has been extensively
      characterized for its role in resistance to alkylating agents used in GBM
      treatment. In the present study, given the major role of angiogenesis and
      invasion in GBM aggressiveness, we aimed to investigate the relationship between
      MGMT expression and GBM invasion. Stable overexpression of MGMT in the U87MG cell
      line significantly decreased invasion, altered expression of invasion-related
      genes, decreased expression of alpha(5)beta(1) integrin and focal adhesion
      kinase, and reduced their spindle-shaped morphology and migration compared with
      the empty vector control. Conversely, short hairpin RNA-mediated stable knockdown
      of MGMT or its pharmacologic depletion in the MGMT-positive T98G cell line were
      required for increased invasion. The inverse relationship between MGMT and
      invasion was further validated in primary GBM patient-derived cell lines. Using
      paraffin-embedded tumors from patients with newly diagnosed GBM (n = 59), tumor
      MGMT promoter hypermethylation (MGMT gene silencing) was significantly associated
      with increased immunohistochemical expression of the proinvasive matricellular
      protein secreted protein acidic and rich in cysteine (SPARC; P = 0.039, chi(2)
      test). Taken together, our findings highlight for the first time the role of MGMT
      as a negative effector of GBM invasion. Future studies are warranted to elucidate
      the role of SPARC in the molecular mechanisms underlying the inverse relationship
      between MGMT and GBM invasion and the potential use of MGMT and SPARC as
      biomarkers of GBM invasion.

PMID- 22986465
TI  - Prenatal determination of the upper lesion level of spina bifida with three
      dimensional ultrasound.
AB  - INTRODUCTION: To evaluate the role of three-dimensional (3D) sonography in the
      prenatal detection of the upper pole in fetuses with spina bifida. MATERIAL AND
      METHODS: Women admitted to a tertiary center with pregnancies with isolated open
      spina bifida were enrolled in the study. All fetuses had 3D sonography to predict
      the lesion level. The exact lesion level was ascertained using radiography and/or
      autopsy following the delivery at term or abortion. RESULTS: Forty-eight cases
      were eligible for this study. Twenty-eight fetuses were diagnosed in the second
      trimester and the lesion level was precisely predicted in 24 (86%) of them. In 14
      (70%) of the 20 fetuses diagnosed in the last trimester, the level was accurately
      determined. The remaining 10 fetuses, from both the second and third trimesters,
      were found to have a lesion level that was within one segment of the predicted
      lesion level. The correct matching rate was 38/48 (79%), and agreement within one
      segment was achieved in all cases. DISCUSSION: According to our data, 3D
      ultrasound is useful for the prenatal determination of lesion level in spina
      bifida, which is an important prognostic factor.

PMID- 22986466
TI  - Changes in serum cytokine and cortisol levels in normothermic and hypothermic
      term neonates after perinatal asphyxia.
AB  - OBJECTIVE: Perinatal asphyxia is characterized by an inflammatory response that
      contributes to cerebral injury. Therapeutic hypothermia improves neurological
      outcome in asphyxiated term neonates, but its clear effect on the inflammatory
      response is unknown. SUBJECTS AND METHODS: A range of cytokines and cortisol
      levels were measured at the 6th, 12th and 24th postnatal hours in neonates with
      hypoxic-ischemic encephalopathy treated with standard intensive care on
      hypothermia (n = 10) or normothermia (n = 8). The influence of postnatal age and
      hypothermia on serum cytokine and cortisol levels was evaluated. RESULTS:
      Interleukin (IL)-6 levels (at 6 h of age) and IL-4 levels (at all time points)
      were significantly lower in asphyxiated neonates treated with hypothermia
      compared to normothermic neonates. Vascular endothelial growth factor levels were
      higher in the hypothermia than in the normothermia group at the 6th and 12th
      postnatal hours. IL-10 levels decreased significantly between 6 and 24 h of age
      in both groups. However, no difference of IL-10 levels was observed between the
      study groups. The duration of hypothermia before 6 hours of age correlated with
      lower levels of IL-6, interferon-gamma and tumor necrosis factor-alpha measured
      at 6 h of age and IL-10 levels at 12 h of age. Cortisol levels did not differ
      between the study groups, but did gradually decrease in both groups during the
      study period. At 6 and 24 h of age, a positive correlation was observed between
      cortisol and IL-10 levels. CONCLUSIONS: Therapeutic hypothermia may rapidly
      suppress and modify the immediate cytokine response to asphyxia. The correlation
      between cytokine levels and duration of hypothermia suggests that the earlier
      hypothermia is introduced, the more pronounced its beneficial immunomodulatory
      effect.

PMID- 22986468
TI  - Deciphering DNA-based asymmetric catalysis through intramolecular Friedel-Crafts
      alkylations.
AB  - We describe asymmetric intramolecular Friedel-Crafts alkylations with a DNA-based
      hybrid catalyst and propose a plausible binding model. This study shows promise
      for studying relationships between the helical chirality of DNA and
      enantioselectivity of the chemical reaction.

PMID- 22986467
TI  - Lipopolysaccharide/adenosine triphosphate-mediated signal transduction in the
      regulation of NLRP3 protein expression and caspase-1-mediated interleukin-1beta
      secretion.
AB  - OBJECTIVE: Reactive oxygen species (ROS) plays a critical role in the regulation
      of NLRP3 inflammasome activation. However, the ROS-mediated signaling pathways
      controlling NLRP3 inflammasome activation are not well defined. METHODS: Using
      lipopolysaccharide (LPS) and adenosine triphosphate (ATP) activated murine
      macrophages as the testing model, cytokine release and protein expression were
      quantified by enzyme-linked immunosorbent assay and Western blot, respectively.
      ROS was scavenged by N-acetyl cysteine; NADPH oxidase, the major source of ROS,
      was inhibited by diphenyliodonium, apocynin or gp91-phox siRNA transfection; and
      protein kinase was inhibited by its specific inhibitor. RESULTS: LPS-induced
      NLRP3 protein expression was regulated through the NADPH oxidase/ROS/NF-kappaB
      dependent, JAK2/PI3-kinase/AKT/NF-kappaB-dependent, and MAPK-dependent pathways,
      while ATP-induced caspase-1 activation was regulated through the NADPH
      oxidase/ROS-dependent pathway. CONCLUSIONS: These results demonstrate that ROS
      regulates not only the priming stage, but also the activation stage, of NLRP3
      inflammasome activation in LPS + ATP-activated macrophages.

PMID- 22986469
TI  - Artificial neural networks for breathing and snoring episode detection in sleep
      sounds.
AB  - Obstructive sleep apnea (OSA) is a serious disorder characterized by intermittent
      events of upper airway collapse during sleep. Snoring is the most common
      nocturnal symptom of OSA. Almost all OSA patients snore, but not all snorers have
      the disease. Recently, researchers have attempted to develop automated snore
      analysis technology for the purpose of OSA diagnosis. These technologies commonly
      require, as the first step, the automated identification of snore/breathing
      episodes (SBE) in sleep sound recordings. Snore intensity may occupy a wide
      dynamic range (> 95 dB) spanning from the barely audible to loud sounds. Low
      intensity SBE sounds are sometimes seen buried within the background noise floor,
      even in high-fidelity sound recordings made within a sleep laboratory. The
      complexity of SBE sounds makes it a challenging task to develop automated snore
      segmentation algorithms, especially in the presence of background noise. In this
      paper, we propose a fundamentally novel approach based on artificial neural
      network (ANN) technology to detect SBEs. Working on clinical data, we show that
      the proposed method can detect SBE at a sensitivity and specificity exceeding
      0.892 and 0.874 respectively, even when the signal is completely buried in
      background noise (SNR < 0 dB). We compare the performance of the proposed
      technology with those of the existing methods (short-term energy, zero-crossing
      rates) and illustrate that the proposed method vastly outperforms conventional
      techniques.

PMID- 22986470
TI  - Treatment of tattoos with a picosecond alexandrite laser: a prospective trial.
AB  - OBJECTIVE To study a picosecond 755-nm alexandrite laser for the removal of
      tattoos to confirm the efficacy of this therapy, focusing on the effect of
      therapy on the target lesion as well as the surrounding tissues and quantifying
      the number of necessary treatments. DESIGN Fifteen patients with tattoos were
      enrolled. Treatments were scheduled approximately 6 +/- 2 weeks apart. Standard
      photographs using 2-dimensional imaging were taken at baseline, before each
      treatment, and 1 month and 3 months after the last treatment. SETTING Dermatology
      clinic at SkinCare Physicians in Chestnut Hill, Massachusetts. PATIENTS Fifteen
      patients with darkly pigmented tattoos. MAIN OUTCOME MEASURES Treatment efficacy
      was assessed by the level of tattoo clearance in standard photographs. These
      photographs were assessed by a blinded physician evaluator and based on a 4-point
      scale. Efficacy was also assessed based on physician and patient satisfaction
      measured on a 4-point scale. RESULTS Twelve of 15 patients with tattoos (80%)
      completed the study. All 12 patients obtained greater than 75% clearance. Nine
      patients (75%) obtained greater than 75% clearance after having 2 to 4
      treatments. The average number of treatment sessions needed to obtain this level
      of clearance was 4.25. All 12 patients (100%) were satisfied or extremely
      satisfied with the treatment. Adverse effects included pain, swelling, and
      blistering. Pain resolved immediately after therapy, while the swelling and
      blistering resolved within 1 week. Hypopigmentation and hyperpigmentation were
      reported at the 3-month follow-up. CONCLUSION The picosecond 755-nm alexandrite
      laser is a safe and very effective procedure for removing tattoo pigment.

PMID- 22986472
TI  - The kaleidoscopic manifestations of systemic vasculitis.

PMID- 22986471
TI  - Microvascular effect of intracoronary eptifibatide in acute myocardial
      infarction.
AB  - OBJECTIVES: In this prospective, randomized trial in patients with acute
      myocardial infarction (AMI) admitted for primary percutaneous coronary
      intervention (PPCI), loaded with 600 mg clopidogrel, we hypothesized that
      eptifibatide administered downstream of the coronary occlusion leads to a lower
      degree of microvascular obstruction compared with no additional eptifibatide.
      METHODS: Fifty patients with AMI, loaded with 600 mg of clopidogrel at the first
      hospital contact, with occlusion of the left anterior descending artery (LAD),
      were randomized to an eptifibatide group (EG) or a control group (CG). In both
      groups, stenting was performed after thrombus aspiration. Microvascular
      reperfusion was assessed by angiography, electrocardiography, and transthoracic
      Doppler ultrasonography of the LAD. RESULTS: TIMI myocardial perfusion grade 2-3
      was not different between the EG (72%) and the CG (84%) (p = 0.31). ST segment
      resolution >70% was similarly detected in both groups (32 vs. 40%; p = 0.56). The
      mean diastolic deceleration time did not differ significantly between the CG
      (856.36 +/- 397.88 ms) and the EG (935.72 +/- 252.22 ms) (p = 0.41). Multivariate
      logistic regression revealed no significant influence of the treatment with
      eptifibatide on ST segment resolution (OR 0.47; 95% CI 0.11-2.10, p = 0.32), TIMI
      myocardial perfusion (OR 0.52; 95% CI 0.10-2.59, p = 0.42), and diastolic
      deceleration time (OR 0.21; 95% CI 0.03-1.51, p = 0.12). CONCLUSIONS: In AMI
      patients loaded with 600 mg of clopidogrel undergoing PPCI, intracoronary
      administration of eptifibatide does not clearly improve microvascular
      obstruction.

PMID- 22986473
TI  - Structural, mechanical and electronic properties of nano-fibriform silica and its
      organic functionalization by dimethyl silane: a SCC-DFTB approach.
AB  - Self-consistent-charge density-functional tight-binding (SCC-DFTB) approximated
      method was employed to investigate the structural, mechanical and electronic
      properties of the zigzag and armchair nano-fibriform silica (SNTs) and their
      outer surface organic modified derivatives (MSNTs) with internal radii in the
      range of 8 to 36 A. The strain energy curves showed that the nanotubes structures
      are energetically more stable compared to the respective sheet structures.
      External hydroxyl dihedral angles in silica nanotubes have small influence, about
      0.5 meV.atom(-1), in the strain energy curve tendency of those materials favoring
      the zigzag chirality. The chemical modification of outer surface of SNTs by
      dimethyl silane group affects their relative stability favoring the armchair
      chirality in approximately 2 meV.atom(-1). MSNTs have axial elastic constants,
      Young's moduli, determined at the harmonic approximation, around 100 GPa smaller
      than the respective SNTs. The Young's moduli of zigzag and armchair SNTs are in
      the range of 150-195 GPa and 232-260 GPa, respectively. And for the zigzag and
      armchair MSNTs these values are in the range of 77-89 and 110-140 GPa,
      respectively. The SNTs and MSNTs were characterized as insulators with band gaps
      around 8-10 eV.

PMID- 22986475
TI  - Thinking outside the bag (not necessarily outside the lab).

PMID- 22986474
TI  - Pressure cycling technology (PCT) reduces effects of inhibitors of the PCR.
AB  - A common problem in the analysis of forensic human DNA evidence, or for that
      matter any nucleic acid analysis, is the presence of contaminants or inhibitors.
      Contaminants may copurify with the DNA, inhibiting downstream PCR or they may
      present samples effectively as containing fewer templates than exist in the PCR,
      even when the actual amount of DNA is adequate. Typically, these challenged
      samples exhibit allele imbalance, allele dropout, and sequence-specific
      inhibition, leading to interpretational difficulties. Lessening the effects of
      inhibitors may increase the effective yield of challenged low template copy
      samples. High pressure may alter some inhibitors and render them less effective
      at reducing the yield of PCR products. In an attempt to enhance the amplicon
      yield of inhibited DNA samples, pressure cycling technology was applied to DNA
      exposed to various concentrations of hematin (0, 1.25, 2.5, 5, and 7 MUM) and
      humic acid (0, 1.25, 2.5, 5, and 7 ng/MUL). The effect of high pressure on the
      inhibitors, and subsequently the PCR process, was assessed by measuring DNA
      quantity by quantitative PCR and evaluating short tandem repeat typing results.
      The results support that pressure cycling technology reduces inhibitory effects
      and thus, in effect, enhances yield of contaminated amplified products of both
      hematin and humic acid contaminate samples. Based on the results obtained in this
      study, this method can improve the ability to type challenged or inhibited DNA
      samples.

PMID- 22986477
TI  - Comments to "Rhabdomyolysis in the US Active Duty Army, 2004-2006".

PMID- 22986481
TI  - POI: a score to modulate GH treatment in children with Prader-Willi syndrome.

PMID- 22986483
TI  - Usefulness of positron emission tomography with fludeoxyglucose f 18 and with
      carbon 11-tagged methionine in the diagnosis of hippocampal lesions.

PMID- 22986482
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptosis by disruption of
      intracellular calcium homeostasis in human neuronal cell line SHSY5Y.
AB  - The persistent xenobiotic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      induces neurotoxic effects that alters neurodevelopment and behavior both during
      development and adulthood. There are many ongoing efforts to determine the
      molecular mechanisms of TCDD-mediated neurotoxicity, the signaling pathways
      involved and its molecular targets in neurons. In this work, we have used SHSY5Y
      human neuroblastoma cells to characterize the TCDD-induced toxicity. TCDD
      produces a loss of viability linked to an increased caspase-3 activity, PARP-1
      fragmentation, DNA laddering, nuclear fragmentation and hypodiploid (apoptotic)
      DNA content, in a similar way than staurosporine, a prototypical molecule of
      apoptosis induction. In addition, TCDD produces a decrease of mitochondrial
      membrane potential and an increase of intracellular calcium concentration (P <
      0.05). Finally, based on the high lipophilic properties of the dioxin, we test
      the TCDD effect on the membrane integrity using sarcoplasmic reticulum vesicles
      as a model. TCDD produces calcium efflux through the membrane and an anisotropy
      decrease (P < 0.05) that reflects an increase in membrane fluidity. Altogether
      these results support the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma
      cells provokes the disruption of calcium homeostasis, probably affecting membrane
      structural integrity, leading to an apoptotic process.

PMID- 22986484
TI  - Correlation between protective immunity to alpha-synuclein aggregates, oxidative
      stress and inflammation.
AB  - OBJECTIVE: Protein aggregation leading to central amyloid deposition is
      implicated in Parkinson's disease (PD). During disease progression, inflammation
      and oxidative stress may well invoke humoral immunity against pathological
      aggregates of PD-associated alpha-synuclein. The aim was to investigate any
      possible concurrence between autoimmune responses to alpha-synuclein monomers,
      oligomers or fibrils with oxidative stress and inflammation. METHODS: The
      formation of alpha-synuclein amyloid species was assessed by thioflavin-T assay
      and atomic force microscopy was employed to confirm their morphology. Serum
      autoantibody titers to alpha-synuclein conformations were determined by ELISA.
      Enzyme activity and concentrations of oxidative stress/inflammatory indicators
      were evaluated by enzyme and ELISA protocols. RESULTS: In PD patient sera, a
      differential increase in autoantibody titers to alpha-synuclein monomers, toxic
      oligomers or fibrils was associated with boosted levels of the pro-inflammatory
      cytokine interleukin-6 and tumour necrosis factor-alpha, but a decrease in
      interferon-gamma concentration. In addition, levels of malondialdehyde were
      elevated whilst those of glutathione were reduced along with decrements in the
      activity of the antioxidants: superoxide dismutase, catalase and glutathione
      transferase. CONCLUSIONS: It is hypothesized that the generation of alpha
      synuclein amyloid aggregates allied with oxidative stress and inflammatory
      reactions may invoke humoral immunity protecting against dopaminergic neuronal
      death. Hence, humoral immunity is a common integrative factor throughout PD
      progression which is directed towards prevention of further neurodegeneration, so
      potential treatment strategies should attempt to maintain PD patient immune
      status.

PMID- 22986485
TI  - Effect of L-thyroxine replacement on apolipoprotein B-48 in overt and subclinical
      hypothyroid patients.
AB  - Apolipoprotein B-48 (ApoB-48) is a constituent of chylomicrons and chylomicron
      remnants, and is thought to be one of the risk factors for atherosclerosis.  We
      evaluated the effect of L-thyroxine (L-T(4)) replacement on serum ApoB-48 levels
      in patients with primary hypothyroidism.  Eighteen patients with overt
      hypothyroidism (OH) and 18 patients with subclinical hypothyroidism (SH)
      participated in the study.  The lipid profiles, including ApoB-48, were measured
      in patients with hypothyroidism before and 3 months after L-T(4) replacement. 
      After L-T(4) replacement, the serum concentrations of all lipoproteins, exclusive
      of lipoprotein(a) (Lp(a)), were significantly decreased in patients with OH.  In
      patents with SH, the serum levels of total cholesterol (TC), non-high-density
      lipoprotein cholesterol (non-HDL-C), remnant-like particle cholesterol (RLP-C),
      apolipoprotein B (ApoB), and ApoB-48 decreased significantly after L-T(4)
      replacement.  The serum levels of triglycerides (TG), HDL-C, low-density
      lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA-1), and Lp(a) did not
      change significantly.  In all 36 patients, the reduction in the ApoB-48 levels
      correlated significantly with the reduction in TSH levels (r = 0.39, P<0.05). 
      This study showed clearly that L-T(4) replacement might reduce serum levels of
      ApoB-48 in both OH and SH patients.  Such altered serum levels of ApoB-48 in
      patients with OH and SH may be related to the disturbed metabolism of chylomicron
      remnants in patients with hypothyroidism.

PMID- 22986486
TI  - Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I)
      in the liver.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play essential roles
      in growth in childhood, and continue to have important metabolic actions in
      adults.  Adult growth hormone deficiency (AGHD) is characterized by increased
      visceral adiposity, abnormal lipid profiles, premature atherosclerosis, decreased
      quality of life, and increased mortality.  Recently, case reports and several
      clinical studies suggest that GHD state in adults is associated with an increased
      prevalence of nonalcoholic fatty liver disease (NAFLD) and progression to
      nonalcoholic steatohepatitis (NASH) or liver cirrhosis.  As a mechanistic
      insight, growing evidence has revealed that GH as well as IGF-I play essential
      roles in the liver.  Further investigation is necessary to clarify the precise
      mechanisms by which GH and IGF-I exert their effects in the liver; however, it
      should be noted that NAFLD/NASH has emerged as an important comorbidity in AGHD.

PMID- 22986487
TI  - Liraglutide prevents diabetes progression in prediabetic OLETF rats.
AB  - One of human GLP-1 analogues, liraglutide has been approved as adjuvant therapy
      to oral medication in T2DM.  It was also shown to prevent diabetes in obese
      subjects and rats.  However, it is unknown whether liraglutide can effectively
      mitigate the effects of prediabetes.  We therefore investigate this by treating
      12-weeks old Otsuka-Long-Evans-Tokushima fatty (OLETF) rats with liraglutide 50,
      100, and 200 MUg/kg, respectively twice a day for 12 weeks.  Eight Long-Evans
      Tokushima-Otsuka (LETO) rats with saline injection served as normal controls. 
      Body weight, food intake, lipid profiles, inflammatory markers (fibrinogen, Hs
      CRP, IL-6, TNFalpha, and PAI-1), glycemic metabolism and insulin sensitivity, and
      apoptotic factors (Bcl-2 and Bax) expression were monitored.  We found that 12
      week old OLETF rats had significantly increased body weight, food intake, serum
      levels of lipid profiles, inflammatory markers, and insulin compared to LETO
      rats.  FPG level was significantly increased but still lower than 7mmol/L without
      impaired glucose tolerance (IGT).  After 12 weeks, vehicle-treated OLETF rats had
      further deterioration in IFG, IGT, insulin resistance, lipid profiles, and
      inflammatory state.  Pancreatic islets were hypertrophic with distorted
      structure, scarring, and inflammatory cell infiltration.  However, in the three
      liraglutide-treated groups, IFG, IGT, the increased lipid profiles and
      inflammatory markers were reversed.  Insulin resistance was similar to the level
      before the treatment.  Moreover, liraglutide restored the islet structure, up
      regulated Bcl-2 expression and down-regulated Bax expression.  It indicated that
      liraglutide could suppress diabetes onset in OLETF rats with prediabetes,
      probably by reserving beta cell function via regulating apoptotic factors as well
      as ameliorating lipid metabolism and inflammatory reactions.

PMID- 22986488
TI  - Ultraviolet B activated 1,25(OH)(2)D affects the level of fibroblast growth
      factor-23 in human.
AB  - Fibroblast growth factor 23 (FGF-23) is known as a phosphaturic factor regulating
      phosphate homeostasis.  Several studies suggest that dietary phosphate, serum
      phosphate and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] are candidate regulators of
      FGF-23.  While the human studies, which modulated the dietary or serum phosphate
      showed in rather controversial results, manipulation of the active vitamin D
      definitely affected FGF-23 in animals.  This study was conducted to elucidate the
      relationship between active vitamin D directly stimulated by ultraviolet B (UVB)
      exposure and FGF-23 level in human.  Ten healthy young adults were recruited to
      get the UVB exposure thrice a week at sub-minimal erythemal dose with gradual
      increment by 10% only for 4 weeks.  Serum calcium, phosphate, mineral-related
      hormones and bone turnover markers were analyzed before and after the UVB
      exposure every 4 week for 12 whole weeks.  Twenty five-hydroxyvitamin D [25(OH)D]
      increased by 115% (19.8 ng/mL to 40.5 ng/mL, p < 0.001) after 4 weeks of UVB
      exposure.  While 1,25(OH)(2)D increased by 75% (49.9 pg/mL to 64.4 pg/mL, p <
      0.001) then both level decreased after 4 weeks of withdrawal.  C-telopeptide
      peaked at 2nd week then decreased, while osteocalcin increased gradually.  FGF-23
      started to increase from the 4th week of UVB exposure then significantly at the
      4th week after withdrawal of UVB (27.8 pg/mL to 41.4 pg/mL, p < 0.05).  UVB
      exposure effectively increased 1,25(OH)(2)D with delayed stimulatory effect on
      FGF-23.  This result could support the regulatory loop of 1,25(OH)(2)D and FGF-23
      in human, FGF-23 regulation by 1,25(OH)(2)D.

PMID- 22986489
TI  - Association of serum YKL-40 levels with urinary albumin excretion rate in young
      Japanese patients with type 1 diabetes mellitus.
AB  - YKL-40 is a marker of inflammation and endothelial dysfunction, both of which
      play important roles in the progression of diabetic complications.  However,
      little information has been obtained about serum YKL-40 levels in type 1 diabetic
      patients. We evaluated YKL-40 levels and its association with diabetic micro- and
      macroandgiopathy in 131 young Japanese type 1 diabetic patients without advanced
      diabetic complications (aged 24.7+/-5.9 years) and 97 age- and gender-matched
      healthy controls.  YKL-40 levels were significantly elevated in type 1 diabetic
      patients than in healthy controls (median (range) 46.4 (20.3-136.7) and 52.3
      (21.4-274.1) ng/mL, respectively, p = 0.003).  There was a significant positive
      association between YKL-40 levels and urinary albumin creatinine ratio (UACR) (r
      = 0.226, p = 0.013).  Furthermore, a multivariate regression analysis
      demonstrated that YKL-40 levels were a determinant of UACR independently of
      conventional risk factors.  In addition, YKL-40 levels were significantly higher
      in participants with diabetic retinopathy compared to those without it (median
      (range) 55.5 (23.3-274.1) and 50.3 (21.4-237.4) ng/mL, respectively, p = 0.039). 
      Serum YKL-40 levels were elevated in type 1 diabetic patients and associated with
      increasing level of albuminuria.  YKL-40 could be a predictor to assess the risk
      of diabetic microangiopathy in the early stage in type 1 diabetic patients.

PMID- 22986490
TI  - Wavelength dependent photocatalytic H2 generation using iridium-Pt/Pd complexes.
AB  - Novel cyclometallated iridium-Pt/Pd dinuclear complexes containing the bridging
      ligand 2,2':5',2''-terpyridine (BPP) and the peripheral phenylpyridine (ppy)
      ligand produced hydrogen under both visible (470 nm) and UV (350 nm) irradiation.
      The turnover numbers using visible light were found to be significantly higher,
      indicating an interplay between two independent excited states, only one of which
      produces H(2) efficiently.

PMID- 22986491
TI  - Wendell Lim: exploring the path not chosen. Interview by Caitlin Sedwick.

PMID- 22986493
TI  - The cellular and molecular basis for malaria parasite invasion of the human red
      blood cell.
AB  - Malaria is a major disease of humans caused by protozoan parasites from the genus
      Plasmodium. It has a complex life cycle; however, asexual parasite infection
      within the blood stream is responsible for all disease pathology. This stage is
      initiated when merozoites, the free invasive blood-stage form, invade circulating
      erythrocytes. Although invasion is rapid, it is the only time of the life cycle
      when the parasite is directly exposed to the host immune system. Significant
      effort has, therefore, focused on identifying the proteins involved and
      understanding the underlying mechanisms behind merozoite invasion into the
      protected niche inside the human erythrocyte.

PMID- 22986494
TI  - Mitotic lamin disassembly is triggered by lipid-mediated signaling.
AB  - Disassembly of the nuclear lamina is a key step during open mitosis in higher
      eukaryotes. The activity of several kinases, including CDK1 (cyclin-dependent
      kinase 1) and protein kinase C (PKC), has been shown to trigger mitotic lamin
      disassembly, yet their precise contributions are unclear. In this study, we
      develop a quantitative imaging assay to study mitotic lamin B1 disassembly in
      living cells. We find that CDK1 and PKC act in concert to mediate phosphorylation
      dependent lamin B1 disassembly during mitosis. Using ribonucleic acid
      interference (RNAi), we showed that diacylglycerol (DAG)-dependent PKCs triggered
      rate-limiting steps of lamin disassembly. RNAi-mediated depletion or chemical
      inhibition of lipins, enzymes that produce DAG, delayed lamin disassembly to a
      similar extent as does PKC inhibition/depletion. Furthermore, the delay of lamin
      B1 disassembly after lipin depletion could be rescued by the addition of DAG.
      These findings suggest that lipins activate a PKC-dependent pathway during
      mitotic lamin disassembly and provide evidence for a lipid-mediated mitotic
      signaling event.

PMID- 22986495
TI  - A PHD12-Snail2 repressive complex epigenetically mediates neural crest epithelial
      to-mesenchymal transition.
AB  - Neural crest cells form within the neural tube and then undergo an epithelial to
      mesenchymal transition (EMT) to initiate migration to distant locations. The
      transcriptional repressor Snail2 has been implicated in neural crest EMT via an
      as of yet unknown mechanism. We report that the adaptor protein PHD12 is highly
      expressed before neural crest EMT. At cranial levels, loss of PHD12 phenocopies
      Snail2 knockdown, preventing transcriptional shutdown of the adhesion molecule
      Cad6b (Cadherin6b), thereby inhibiting neural crest emigration. Although not
      directly binding to each other, PHD12 and Snail2 both directly interact with
      Sin3A in vivo, which in turn complexes with histone deacetylase (HDAC). Chromatin
      immunoprecipitation revealed that PHD12 is recruited to the Cad6b promoter during
      neural crest EMT. Consistent with this, lysines on histone 3 at the Cad6b
      promoter are hyperacetylated before neural crest emigration, correlating with
      active transcription, but deacetylated during EMT, reflecting the repressive
      state. Knockdown of either PHD12 or Snail2 prevents Cad6b promoter deacetylation.
      Collectively, the results show that PHD12 interacts directly with Sin3A/HDAC,
      which in turn interacts with Snail2, forming a complex at the Cad6b promoter and
      thus revealing the nature of the in vivo Snail repressive complex that regulates
      neural crest EMT.

PMID- 22986498
TI  - Prostate cancer: Quality of life factors predict satisfaction with care.

PMID- 22986496
TI  - INF2 promotes the formation of detyrosinated microtubules necessary for
      centrosome reorientation in T cells.
AB  - T cell antigen receptor-proximal signaling components, Rho-family GTPases, and
      formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation
      to the immunological synapse of T lymphocytes. However, the role of these
      molecules in the reorientation process is not yet defined. Here we find that a
      subset of microtubules became rapidly stabilized and that their alpha-tubulin
      subunit posttranslationally detyrosinated after engagement of the T cell
      receptor. Formation of stabilized, detyrosinated microtubules required the formin
      INF2, which was also found to be essential for centrosome reorientation, but it
      occurred independently of T cell receptor-induced massive tyrosine
      phosphorylation. The FH2 domain, which was mapped as the INF2 region involved in
      centrosome repositioning, was able to mediate the formation of stable,
      detyrosinated microtubules and to restore centrosome translocation in DIA1-,
      FMNL1-, Rac1-, and Cdc42-deficient cells. Further experiments indicated that
      microtubule stabilization was required for centrosome polarization. Our work
      identifies INF2 and stable, detyrosinated microtubules as central players in
      centrosome reorientation in T cells.

PMID- 22986497
TI  - Temporal sampling, resetting, and adaptation orchestrate gradient sensing in
      sperm.
AB  - Sperm, navigating in a chemical gradient, are exposed to a periodic stream of
      chemoattractant molecules. The periodic stimulation entrains Ca(2+) oscillations
      that control looping steering responses. It is not known how sperm sample
      chemoattractant molecules during periodic stimulation and adjust their
      sensitivity. We report that sea urchin sperm sampled molecules for 0.2-0.6 s
      before a Ca(2+) response was produced. Additional molecules delivered during a
      Ca(2+) response reset the cell by causing a pronounced Ca(2+) drop that
      terminated the response; this reset was followed by a new Ca(2+) rise. After
      stimulation, sperm adapted their sensitivity following the Weber-Fechner law.
      Taking into account the single-molecule sensitivity, we estimate that sperm can
      register a minimal gradient of 0.8 fM/um and be attracted from as far away as 4.7
      mm. Many microorganisms sense stimulus gradients along periodic paths to
      translate a spatial distribution of the stimulus into a temporal pattern of the
      cell response. Orchestration of temporal sampling, resetting, and adaptation
      might control gradient sensing in such organisms as well.

PMID- 22986500
TI  - Male factor infertility: Asymptomatic testicular microlithiasis does not increase
      antisperm antibody production in infertile men.

PMID- 22986499
TI  - Prostate cancer: Is aspirin a wonder drug in prostate cancer?

PMID- 22986501
TI  - Dendritic self-avoidance: protocadherins have it covered.
AB  - Dendrites exhibit self-avoidance, in which branches of the same neuron repel each
      other while overlapping with branches from neighboring neurons. A recent paper by
      Lefebvre and colleagues reveals that clustered protocadherins provide a basis for
      neuronal recognition during dendrite self-avoidance in vertebrates.

PMID- 22986502
TI  - A functional variant in the cystathionine beta-synthase gene promoter
      significantly reduces congenital heart disease susceptibility in a Han Chinese
      population.
AB  - Homocysteine is an independent risk factor for various cardiovascular diseases.
      There are two ways to remove homocysteine from embryonic cardiac cells:
      remethylation to form methionine or transsulfuration to form cysteine.
      Cystathionine beta-synthase (CBS) catalyzes the first step of homocysteine
      transsulfuration as a rate-limiting enzyme. In this study, we identified a
      functional variant -4673C>G (rs2850144) in the CBS gene promoter region that
      significantly reduces the susceptibility to congenital heart disease (CHD) in a
      Han Chinese population consisting of 2 340 CHD patients and 2 270 controls.
      Individuals carrying the heterozygous CG and homozygous GG genotypes had a 15%
      (odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.75-0.96, P = 0.011) and
      40% (OR = 0.60, 95% CI = 0.49-0.73, P = 1.78 * 10(-7)) reduced risk to develop
      CHD than the wild-type CC genotype carriers in the combined samples,
      respectively. Additional stratified analyses demonstrated that CBS -4673C>G is
      significantly related to septation defects and conotruncal defects. In vivo
      detection of CBS mRNA levels in human cardiac tissues and in vitro luciferase
      assays consistently showed that the minor G allele significantly increased CBS
      transcription. A functional analysis revealed that both the attenuated
      transcription suppressor SP1 binding affinity and the CBS promoter
      hypomethylation specifically linked with the minor G allele contributed to the
      remarkably upregulated CBS expression. Consequently, the carriers with
      genetically increased CBS expression would benefit from the protection due to the
      low homocysteine levels maintained by CBS in certain cells during the critical
      heart development stages. These results shed light on unexpected role of CBS and
      highlight the importance of homocysteine removal in cardiac development.Cell
      Research advance online publication 18 September 2012; doi:10.1038/cr.2012.135.

PMID- 22986503
TI  - A new horizon for epigenetic medicine?
AB  - Histone lysine demethylases are chromatin modifiers that play important roles in
      many pathological processes such as inflammation and cancer, making them
      potentially attractive drug targets. In a recent study, Kruidenier et al.
      provided proof of concept by identifying chemical matters that inhibit
      demethylation mediated by the two related histone H3 lysine 27 demethylases,
      KDM6A and 6B (UTX and JMJD3). The KDM6 inhibitor shows remarkable substrate
      selectivity and can inhibit transcription of a plethora of pro-inflammatory genes
      in cell culture by altering H3K27me3 level at some of the KDM6 target genes.

PMID- 22986504
TI  - Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2.
AB  - Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult
      tissue homeostasis in species ranging from Drosophila to mammals. The Hh signal
      is transduced by Smoothened (Smo), a seven-transmembrane protein related to G
      protein coupled receptors. Despite a conserved mechanism by which Hh activates
      Smo in Drosophila and mammals, how mammalian Hh signal is transduced from Smo to
      the Gli transcription factors is poorly understood. Here, we provide evidence
      that two ciliary proteins, Evc and Evc2, the products of human disease genes
      responsible for the Ellis-van Creveld syndrome, act downstream of Smo to
      transduce the Hh signal. We found that loss of Evc/Evc2 does not affect Sonic
      Hedgehog-induced Smo phosphorylation and ciliary localization but impedes Hh
      pathway activation mediated by constitutively active forms of Smo. Evc/Evc2 are
      dispensable for the constitutive Gli activity in Sufu(-/-) cells, suggesting that
      Evc/Evc2 act upstream of Sufu to promote Gli activation. Furthermore, we
      demonstrated that Hh stimulates binding of Evc/Evc2 to Smo depending on
      phosphorylation of the Smo C-terminal intracellular tail and that the binding is
      abolished in Kif3a(-/-) cilium-deficient cells. We propose that Hh activates Smo
      by inducing its phosphorylation, which recruits Evc/Evc2 to activate Gli proteins
      by antagonizing Sufu in the primary cilia.

PMID- 22986505
TI  - Comparing proximal and distal metatarsal osteotomy for moderate to severe hallux
      valgus.
AB  - PURPOSE: This study compared results of distal and proximal metatarsal osteotomy
      for moderate to severe hallux valgus in terms of radiographic correction and
      functional outcome. METHODS: We analyzed 125 moderate to severe hallux valgus
      surgeries. Patients were divided into two groups. Group 1 underwent distal
      metatarsal osteotomy, and group 2 underwent proximal metatarsal osteotomy.
      Patients were interviewed for functional scores before and one year after
      surgery. The anteroposterior (AP) weight-bearing radiography of the foot was
      taken before and one year after surgery. RESULTS: There were no significant
      differences in pain and function after one year in either group. Both groups
      experienced significant pain reduction and increase in all functional scores.
      There was significant improvement of hallux valgus and intermetatarsal angle
      corrections in group 2. There was less improvement in radiographic correction in
      group 1. CONCLUSION: Either distal or proximal metatarsal osteotomy is an
      appropriate pain-relieving procedure and can increase functional outcome in
      moderate to severe hallux valgus. However, distal metatarsal osteotomy provides
      lower correction power.

PMID- 22986506
TI  - Measurement of cardiac output during exercise in healthy, trained humans using
      lithium dilution and pulse contour analysis.
AB  - The aim of this study was to evaluate the use of pulse contour analysis
      calibrated with lithium dilution in a single device (LiDCO) for measurement of
      cardiac output (Q) during exercise in healthy volunteers. We sought to; (a)
      compare pulse contour analysis (PulseCO) and lithium indicator dilution (LiDCO)
      for the measurement of Q during exercise, and (b) assess the requirement for
      recalibration of PulseCO with LiDCO during exercise. Ten trained males performed
      multi-stage cycling exercise at intensities below and above ventilatory threshold
      before constant load maximal exercise to exhaustion. Uncalibrated PulseCO Q
      (Qraw) was compared to that calibrated with lithium dilution at baseline
      Qbaseline, during submaximal exercise below (Qlow) and above (Qhigh) ventilatory
      threshold, and at each exercise stage individually (Qexercise). There was a
      significant difference between Qbaseline and all other calibration methods during
      exercise, but not at rest. No significant differences were observed between other
      methods. Closest agreement with Qexercise was observed for Qhigh (bias +/- limits
      of agreement: 4.8 +/- 30.0%). The difference between Qexercise and both Qlow and
      Qraw was characterized by low bias (4-7%) and wide limits of agreement (> +/-
      40%). Calibration of pulse contour analysis with lithium dilution prior to
      exercise leads to a systematic overestimation of exercising cardiac output. A
      single calibration performed during exercise above the ventilatory threshold
      provided acceptable limits of agreement with an approach incorporating multiple
      calibrations throughout exercise. Pulse contour analysis may be used for Q
      measurement during exercise providing the system is calibrated during exercise.

PMID- 22986508
TI  - Quantitative microtiter fibronectin fibrillogenesis assay: use in high throughput
      screening for identification of inhibitor compounds.
AB  - Fibronectin (FN) is a plasma glycoprotein that circulates in the near micromolar
      concentration range and is deposited along with locally produced FN in the
      extracellular matrices of many tissues. The control of FN deposition is tightly
      controlled by cells. Agents that modulate FN assembly may be useful
      therapeutically in conditions characterized by excessive FN deposition, such as
      fibrosis, inflammatory diseases, and malignancies. To identify such agents by
      high throughput screening (HTS), we developed a microtiter assay of FN deposition
      by human fibroblasts. The assay provides a robust read-out of FN assembly. Alexa
      488-FN (A488-FN) was added to cell monolayers, and the total fluorescence
      intensity of deposited A488-FN was quantified. The fluorescence intensity of
      deposited A488-FN correlated with the presence of FN fibrils visualized by
      fluorescence microscopy. The assay Z' values were 0.67 or 0.54, respectively,
      when using background values of fluorescence either with no added A488-FN or with
      A488-FN added together with a known inhibitor of FN deposition. The assay was
      used to screen libraries comprising 4160 known bioactive compounds. Nine
      compounds were identified as non- or low-cytotoxic inhibitors of FN assembly.
      Four (ML-9, HA-100, tyrphostin and imatinib mesylate) are kinase inhibitors, a
      category of compounds known to inhibit FN assembly; two (piperlongumine and
      cantharidin) are promoters of cancer cell apoptosis; and three (maprotiline,
      CGS12066B, and aposcopolamine) are modulators of biogenic amine signaling. The
      latter six compounds have not been recognized heretofore as affecting FN
      assembly. The assay is straight-forward, adapts to 96- and 384-well formats, and
      should be useful for routine measurement of FN deposition and HTS. Screening of
      more diverse chemical libraries and identification of specific and efficient
      modulators of FN fibrillogenesis may result in therapeutics to control excessive
      connective tissue deposition.

PMID- 22986510
TI  - Detection of promoter methylation of tumor suppressor genes in serum DNA of
      breast cancer cases and benign breast disease controls.
AB  - Tumors are capable of shedding DNA into the blood stream. This shed DNA may be
      recovered from serum or plasma. The objective of this study was to evaluate
      whether pyrosequencing promoter DNA in a panel of 12 breast cancer-related genes
      (APC, BRCA1, CCND2, CDH1, ESR1, GSTP1, HIN1, P16, RARbeta, RASSF1, SFRP1 and
      TWIST) to measure the degree of methylation would lead to a useful serum-based
      marker of breast cancer. Serum was obtained from women who were about to undergo
      a breast biopsy or mastectomy at three hospitals from 1977 to 1987 in Grand
      Rapids, MI USA. We compared the methylation status of 12 genes in serum DNA
      obtained from three groups of postmenopausal women (mean age at blood collection:
      63.0 y; SD 9.9; range 35-91): breast cancer cases with lymph node-positive
      disease (n = 241); breast cancer cases with lymph node-negative disease (n = 63);
      and benign breast disease control subjects (n = 234). Overall, median levels of
      promoter methylation were low, typically below 5%, for all genes in all study
      groups. For all genes, median levels of methylation were higher (by 3.3 to 47.6%)
      in lymph node-positive breast cancer cases than in the controls. Comparing mean
      methylation level between lymph-node positive cases and controls, the most
      statistically significant findings, after adjustment of the false-positive rate
      (q-value), were for TWIST (p = 0.04), SFRP1 (p = 0.16), ESR1 (p = 0.17), P16 (p =
      0.19) and APC (p = 0.19). For two of these four genes (TWIST, P16), the median
      methylation level was also highest in lymph-node positive cases, intermediate in
      lymph node-negative cases and lowest in the controls. The percent of study
      subjects with mean methylation scores >= 5% was higher among lymph node-positive
      cases than controls for ten genes, and significantly higher for HIN1 and TWIST
      (22.0 vs. 12.2%, p = 0.04 and 37.9 vs. 24.5%, p = 0.004, respectively). Despite
      relatively consistent variation in methylation patterns among groups, these
      modest differences did not provide sufficient ability to distinguish between
      cases and controls in a clinical setting.

PMID- 22986511
TI  - Spatiotemporal pattern formation in two-dimensional neural circuits: roles of
      refractoriness and noise.
AB  - Refractoriness is one of the most fundamental states of neural firing activity,
      in which neurons that have just fired are unable to produce another spike,
      regardless of the strength of afferent stimuli. Another essential and unavoidable
      feature of neural systems is the existence of noise. To study the role of these
      essential factors in spatiotemporal pattern formation in neural systems, a
      spatially expended neural network model is constructed, with the dynamics of its
      individual neurons capturing the three most essential states of the neural firing
      behavior: firing, refractory and resting, and the network topology consistent
      with the widely observed center-surround coupling manner in the real brain. By
      changing the refractory period with and without noise in a systematic way in the
      network, it is shown numerically and analytically that without refractoriness, or
      when the refractory period is smaller than a certain value, the collective
      activity pattern of the system consists of localized, oscillating patterns.
      However, when the refractory period is greater than a certain value, crescent
      shaped, localized propagating patterns emerge in the presence of noise. It is
      further illustrated that the formation of the dynamical spiking patterns is due
      to a symmetry breaking mechanism, refractoriness-induced symmetry breaking; that
      is generated by the interplay of noise and refractoriness in the network model.
      This refractoriness-induced symmetry breaking provides a novel perspective on the
      emergence of localized, spiking wave patterns or spike timing sequences as
      ubiquitously observed in real neural systems; it therefore suggests that
      refractoriness may benefit neural systems in their temporal information
      processing, rather than limiting the performance of neurons, as has been
      conventionally thought. Our results also highlight the importance of considering
      noise in studying spatially extended neural systems, where it may facilitate the
      formation of spatiotemporal order.

PMID- 22986512
TI  - Dopa-responsive dystonia revisited: diagnostic delay, residual signs, and
      nonmotor signs.
AB  - OBJECTIVE: To investigate the delay in diagnosis, residual motor signs, and
      nonmotor signs of dopa-responsive dystonia (DRD) using literature and our own
      pilot data. DESIGN, SETTING, AND PATIENTS: We searched the MEDLINE database for
      patients with clinically typical DRD and/or guanosine triphosphate cyclohydrolase
      I gene mutations from 1952 to 2011 and examined a pilot cohort of 23 outpatients
      with DRD and guanosine triphosphate cyclohydrolase I gene mutations. RESULTS: The
      literature search yielded 101 reports describing 576 cases. Excluding cases
      without proven guanosine triphosphate cyclohydrolase I gene mutations as well as
      homozygous and asymptomatic mutation carriers resulted in 352 cases. The mean
      (SD) ages at onset were 11.6 (13.4) years (literature) and 9.4 (7.7) years (pilot
      study). The average (SD) delays in diagnosis were 13.5 (13.3) years (literature)
      and 15.5 (16.3) years (pilot study); using all literature cases, they were 9.1
      (7.5) years before and 15.2 (13.7) years after identification of the guanosine
      triphosphate cyclohydrolase I gene. Residual motor signs in patients receiving
      therapy were found in 28% (literature) and 39% (pilot study). Residual motor
      signs in the literature comprised dystonic (20%) and parkinsonian (11%) symptoms,
      as well as complications such as contractures or unnecessary surgical procedures.
      Information on nonmotor signs was given for 70 patients in the literature. Of
      these, 34% had depression, 19% anxiety, and 9% obsessive-compulsive disorder. Six
      of our own cases (32%) reported 1 or more nonmotor signs including depression and
      migraine. CONCLUSIONS: The delay in diagnosis is long, despite the well-known
      etiology and availability of genetic testing and specific therapy. A sizable
      number of treated patients have residual motor signs, nonmotor signs, and
      complications resulting from the lack of timely therapy or unnecessary
      procedures.

PMID- 22986513
TI  - Reversible luminescence switching between single and dual emissions of
      bipyridinium-type organic crystals.
AB  - An excitation-wavelength-dependent luminescence behavior of a bipyridinium
      derivative, together with its luminescence switching between single- and dual
      emissions upon reversible solid state structural transformation, has been
      presented.

PMID- 22986507
TI  - Multiple roles for the actin cytoskeleton during regulated exocytosis.
AB  - Regulated exocytosis is the main mechanism utilized by specialized secretory
      cells to deliver molecules to the cell surface by virtue of membranous containers
      (i.e., secretory vesicles). The process involves a series of highly coordinated
      and sequential steps, which include the biogenesis of the vesicles, their
      delivery to the cell periphery, their fusion with the plasma membrane, and the
      release of their content into the extracellular space. Each of these steps is
      regulated by the actin cytoskeleton. In this review, we summarize the current
      knowledge regarding the involvement of actin and its associated molecules during
      each of the exocytic steps in vertebrates, and suggest that the overall role of
      the actin cytoskeleton during regulated exocytosis is linked to the architecture
      and the physiology of the secretory cells under examination. Specifically, in
      neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small
      secretory vesicles that undergo rapid exocytosis (on the order of milliseconds),
      the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily
      as a functional barrier and facilitates docking. In exocrine and other secretory
      cells, which contain large secretory vesicles that undergo slow exocytosis
      (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events,
      where it regulates the dynamics of the fusion pore, facilitates the integration
      of the vesicles into the plasma membrane, provides structural support, and
      promotes the expulsion of large cargo molecules.

PMID- 22986514
TI  - Inflammatory/stress feedback dysregulation in women with fibromyalgia.
AB  - OBJECTIVE: Although one of the current hypotheses of the aetiology of
      fibromyalgia (FM) syndrome involves inflammatory and neuroendocrine disorders,
      its biophysiology still remains unclear. The purpose of the present investigation
      was to study the systemic inflammatory and stress responses, as well as the
      innate response mediated by monocytes and neutrophils in FM patients. METHODS:
      Twenty-five women diagnosed with primary FM and 20 age-matched healthy women
      (control group) were enrolled in the study. Circulating 'neuroendocrine-stress'
      biomarkers (CRH, ACTH, cortisol, NA, eHsp72, serotonin and IGF-1) were evaluated
      by ELISA. Serum IL-8 and CRP concentrations were also determined by ELISA, and
      inflammatory cytokine release by monocytes [IL-1beta, TNFalpha, IL-6, IL-10, IL
      18, monocyte chemotactic protein-1 (MCP-1) and RANTES] was evaluated by the
      Luminex BioPlex system. The phagocytic process of neutrophils (chemotaxis,
      phagocytosis and microbicide capacity) was also evaluated. RESULTS: FM patients
      showed an inflammatory state accompanied by an altered stress response. This is
      mainly manifested by high circulating levels of IL-8 and CRP (in 100% of the FM
      group), high circulating levels of cortisol, and increased systemic levels of NA
      and eHsp72. There is also increased release of inflammatory cytokines (IL-1beta,
      TNFalpha, IL-6, IL-10, IL-18 and MCP-1) by monocytes, and enhanced activation of
      the functional capacity of neutrophils (chemotactic, phagocytic and fungicidal
      activities). CONCLUSION: An inflammatory/stress feedback dysregulation underlies
      FM. Whether dysregulation of the stress response is the cause of the inflammatory
      dysregulation or vice versa is also discussed.

PMID- 22986515
TI  - Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis
      without delayed endothelial healing effects in a porcine coronary artery model.
AB  - AIM: The use of currently marketed drug-eluting stents presents safety concerns
      including increased late thrombosis, which is thought to result mainly from
      delayed endothelial healing effects (impaired re-endothelialization resulting in
      abnormal inflammation and fibrin deposition). We recently developed a
      bioabsorbable polymeric nanoparticle (NP)-eluting stent using a novel cationic
      electrodeposition technology. Statins are known to inhibit the proliferation of
      vascular smooth muscle cells (VSMC) and to promote vascular healing. We therefore
      hypothesized that statin-incorporated NP-eluting stents would attenuate in-stent
      stenosis without delayed endothelial healing effects. METHODS: Among six marketed
      statins, pitavastatin (Pitava) was found to have the most potent effects on VSMC
      proliferation and endothelial regeneration in vitro. We thus formulated a Pitava
      NP-eluting stent (20ug Pitava per stent). RESULTS: In a pig coronary artery
      model, Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as
      polymer-coated sirolimus-eluting stents (SES). At SES sites, delayed endothelial
      healing effects were noted, whereas no such effects were observed in Pitava-NP
      eluting stent sites. CONCLUSION: Pitava-NP-eluting stents attenuated in-stent
      stenosis as effectively as SES without the delayed endothelial healing effects of
      SES in a porcine coronary artery model. This nanotechnology platform could be
      developed into a safer and more effective device in the future.

PMID- 22986516
TI  - Health economics and policy: towards the undiscovered country of market based
      reform.

PMID- 22986517
TI  - Photodynamic properties of vital dyes for vitreoretinal surgery.
AB  - The purpose of this study was to evaluate photodynamic properties of indocyanine
      green (ICG), brilliant blue G (BBG) and trypan blue (TB) as currently used vital
      dyes for chromovitrectomy. Under consideration of intraoperative illumination
      intensities and dye concentrations, a simulative in vitro investigation was set
      up. Therefore, standardized dilutions of original ICG, BBG and TB vials were
      irradiated at a wavelength of 366 nm with an intensity of 14 uW/cm2 between 0 and
      48 h. After this, all samples were measured spectroscopically in a 220- to 750-nm
      bandwidth. Analyzing the vital dyes over the time course, an exponential
      photolysis was observed for ICG, whereas BBG and TB presented photostable
      properties. Regarding ICG, 5% of the concentration was degraded to toxic
      metabolites every 20 min. For this reason, our study provides evidence that
      intraocular dye concentrations and modern endoillumination systems alone cannot
      fully prevent ICG photodegradation.

PMID- 22986518
TI  - Clinical and sociodemographic characteristics associated with thick melanomas. A
      population-based, case-case study in France.
AB  - OBJECTIVE: To identify clinical and sociodemographic factors associated with very
      thick melanoma (VTM) (Breslow thickness, 3 mm) in France. DESIGN: Retrospective,
      population-based, case-case study using a survey of cancer registries and
      questionnaires to practitioners. SETTING: Five regions covering 19.2% of the
      French territory and 8.2 million inhabitants. CASES: Cases included all incident
      melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed
      between January 1 and December 31, 2008, in residents of the study area (Alsace,
      Bourgogne, Champagne-Ardenne, Franche-Comte', and Lorraine, France), and a
      randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES:
      Circumstances of diagnosis,clinical and pathological characteristics of
      melanomas,and sociodemographic characteristics of patients(age, sex, residence,
      home and family life conditions, educational level, and smoking habits). RESULTS:
      Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often
      diagnosed in a general-practice setting than thinner melanomas.The rate of
      immediate clinical recognition by dermatologists was lower for VTMs than for
      thinner melanomas. In a multivariate logistic regression analysis,factors
      associated with VTM were the nodular and acrolentiginous types; the head and neck
      and lower limb locations; older age; male sex; and being single,
      separated,divorced, or widowed. When only factors related to patients were taken
      into account, older age, male sex,and living alone were independent risk factors
      for VTM.The most significant risk was observed for patients living alone.
      CONCLUSIONS: Intrinsic factors related to the tumor and socio demographic
      characteristics of patients contribute to the occurrence of VTM. These factors
      should be better targeted in future secondary prevention programs.

PMID- 22986519
TI  - Have sex or not? Lessons from bacteria.
AB  - Sex is one of the greatest puzzles in evolutionary biology. A true meiotic
      process occurs only in eukaryotes, while in bacteria, gene transcription is
      fragmentary, so asexual reproduction in this case really means clonal
      reproduction. Sex could stem from a signal that leads to increased reproductive
      output of all interacting individuals and could be understood as a secondary
      consequence of primitive metabolic reactions. Meiotic sex evolved in proto
      eukaryotes to solve a problem that bacteria did not have, namely a large amount
      of DNA material, occurring in an archaic step of proto-cell formation and genetic
      exchanges. Rather than providing selective advantages through reproduction, sex
      could be thought of as a series of separate events which combines step-by-step
      some very weak benefits of recombination, meiosis, gametogenesis and syngamy.

PMID- 22986520
TI  - The association between nonalcoholic fatty liver disease, metabolic syndrome and
      arterial stiffness in nondiabetic, nonhypertensive individuals.
AB  - OBJECTIVES: To assess the relationship between nonalcoholic fatty liver disease
      (NAFLD) and arterial stiffness in nondiabetic, nonhypertensive individuals with
      and without metabolic syndrome (MetS). METHODS: Hepatic ultrasound and brachial
      ankle pulse wave velocity (baPWV) were investigated in 4,467 individuals. The
      subjects were classified into normal PWV and increased PWV (>= 1,366 cm/s)
      groups, and divided into 2 groups (non-NAFLD vs. NAFLD groups) and 3 groups (non
      , mild and moderate-to-severe NAFLD groups), respectively. RESULTS: The overall
      prevalence of NAFLD was 37.3% and the NAFLD group had higher levels of baPWV
      (control vs. NAFLD, 1,363 +/- 210.3 vs. 1,388 +/- 235.9 cm/s, p < 0.001). On
      multivariate regression analysis, NAFLD was independently associated with
      increased baPWV (>= 1,366 cm/s), irrespective of multiple covariates (OR 1.237
      and 95% CI 1.050-1.458). Subgroup analyses revealed that there was a significant
      association between NAFLD and baPWV only in individuals without MetS (OR 1.267
      and 95% CI 1.065-1.507). The multivariate linear regression models for the
      overall study population and for individuals without MetS also revealed a
      significant association between NAFLD and the absolute value of baPWV; however,
      the result for individuals with MetS did not. CONCLUSIONS: Our results indicate
      that the presence and the degree of NAFLD are associated with arterial stiffness
      in nonhypertensive, nondiabetic individuals, especially in those individuals
      without MetS.

PMID- 22986521
TI  - SUMOylation of ZFP282 potentiates its positive effect on estrogen signaling in
      breast tumorigenesis.
AB  - Estrogen receptor alpha (ERalpha) has critical roles in the development and
      progression of breast cancer, and the coiled-coil co-activator (CoCoA) is an
      important ERalpha co-activator for estrogen-induced gene expression. The small
      ubiquitin-like modifier (SUMO) pathway is hyperactivated in breast cancer, but
      the mechanism by which SUMOylation regulates ERalpha-mediated transcription
      remains poorly understood. Here, we identified ZFP282 as a CoCoA-binding protein.
      ZFP282 associates directly with ERalpha and cooperates synergistically with CoCoA
      to enhance ERalpha function. ZFP282 is required for estrogen-induced expression
      of ERalpha target genes and estrogen-dependent breast cancer cell growth and
      tumorigenesis. In addition, we found that ZFP282 is SUMOylated and that
      SUMOylation positively regulates the co-activator activity of ZFP282 by
      increasing its binding affinity to ERalpha and CoCoA, and consequently increasing
      recruitment of ZFP282-CoCoA complex to the promoter of ERalpha target genes.
      These findings reveal essential roles for ZFP282 and its SUMOylation in estrogen
      signaling and breast tumorigenesis.

PMID- 22986523
TI  - The E6AP E3 ubiquitin ligase regulates the cellular response to oxidative stress.
AB  - The E6AP E3 ubiquitin ligase has been linked to the regulation of cell growth and
      to the cellular stress response. However, the specific stress conditions that are
      controlled by E6AP have not been defined. An important stress condition that
      controls cell growth is oxidative stress, where the levels of intracellular
      reactive oxygen species (ROS) regulate the appropriate cellular response. Here,
      we describe a novel role for E6AP in the control of oxidative stress response.
      Cells lacking E6AP expression have reduced capacity to accumulate ROS, and
      oxidative DNA damage, in response to 20% cell culture oxygen levels, treatment
      with hydrogen peroxide and expression of oncogenic RAS. This effect of E6AP is
      associated with the regulation of the anti-oxidant enzyme, Prx1, a previously
      identified target of E6AP, and can be corrected by downregulation of Prx1 or by
      reconstitution of E6AP expression. Consequently, cells with compromised E6AP have
      impaired senescent and apoptotic response to sub-lethal and lethal doses of
      oxidative stress, respectively. In a xenograft model, downregulation of E6AP
      renders transplanted tumours refractory to growth-suppressive effects of hydrogen
      peroxide. Our results provide the first demonstration that E6AP is an important
      regulator of ROS-mediated cellular senescence and cell death. 

PMID- 22986522
TI  - Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting
      epithelial-to-mesenchymal transition in an orthotopic model.
AB  - Deguelin is known to suppress the growth of cancer cells; however, its anti
      metastatic effects have not been studied so far in any cancer model. In the
      present study, we aimed to evaluate the anti-metastatic potential of deguelin in
      vivo and in tumor growth factor-beta1 (TGFbeta1)-stimulated cells. Our results
      demonstrate that tumor growth, peritoneal dissemination and liver/lung metastasis
      of orthotopically implanted PanC-1-luc cells were significantly reduced in
      deguelin-treated mice along with the induction of apoptosis. Furthermore,
      deguelin-treated tumors showed increased epithelial signature such as increased
      expression of E-Cadherin and cytokeratin-18 and decreased expression of Snail.
      Similar observations were made when PanC-1, COLO-357 and L3.6pl cells were
      treated in vitro with deguelin. Moreover, E-cadherin was transcriptionally
      upregulated and accumulated in the membrane fraction of deguelin-treated cells,
      as indicated by increased interaction of E-Cadherin with beta-catenin. TGFbeta1
      induced downregulation of E-Cadherin and upregulation of Snail were abrogated by
      deguelin treatment. In addition, deguelin inhibited TGFbeta1-induced Smad3
      phosphorylation and Smad4 nuclear translocation in PanC-1 cells. Furthermore,
      when TGFbeta1-induced nuclear factor kappa B (NFkappaB) activation was inhibited,
      TGFbeta1-induced Snail upregulation or E-Cadherin downregulation was blocked.
      Deguelin also significantly downregulated the constitutive phosphorylation and
      DNA binding of NFkappaB in a dose-dependent manner. Interestingly, overexpression
      of either NFkappaB or Snail completely abrogated deguelin-mediated epithelial-to
      mesenchymal transition (EMT) inhibition, whereas overexpression of NFkappaB but
      not Snail rescued cells from deguelin-induced apoptosis. Hence, deguelin targets
      NFkappaB to induce reversal of EMT and apoptosis but downstream effectors might
      be different for both processes. Taken together, our results suggest that
      deguelin suppresses both pancreatic tumor growth and metastasis by inducing
      apoptosis and inhibiting EMT.

PMID- 22986524
TI  - EZH2 promotes a bi-lineage identity in basal-like breast cancer cells.
AB  - The mechanisms regulating breast cancer differentiation state are poorly
      understood. Of particular interest are molecular regulators controlling the
      highly aggressive and poorly differentiated traits of basal-like breast
      carcinomas. Here we show that the Polycomb factor EZH2 maintains the
      differentiation state of basal-like breast cancer cells, and promotes the
      expression of progenitor associated and basal-lineage genes. Specifically, EZH2
      regulates the composition of basal-like breast cancer cell populations by
      promoting a 'bi-lineage' differentiation state, in which cells co-express basal-
      and luminal-lineage markers. We show that human basal-like breast cancers contain
      a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to
      tumors with a decreased proportion of such cells. Bi-lineage cells express genes
      that are active in normal luminal progenitors, and possess increased colony
      formation capacity, consistent with a primitive differentiation state. We found
      that GATA3, a driver of luminal differentiation, performs a function opposite to
      EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene
      expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi
      lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling
      basal-like breast cancer differentiation state and intra-tumoral cell
      composition.

PMID- 22986525
TI  - MicroRNA-106b-25 cluster expression is associated with early disease recurrence
      and targets caspase-7 and focal adhesion in human prostate cancer.
AB  - The miR-106b-25 microRNA (miRNA) cluster is a candidate oncogene in human
      prostate cancer. Here, we report that miRNAs encoded by miR-106b-25 are
      upregulated in both primary tumors and distant metastasis. Moreover, increased
      tumor miR-106b expression was associated with disease recurrence and the
      combination of high miR-106b and low CASP7 (caspase-7) expressions in primary
      tumors was an independent predictor of early disease recurrence (adjusted hazard
      ratio=4.1; 95% confidence interval: 1.6-12.3). To identify yet unknown oncogenic
      functions of miR-106b, we overexpressed it in LNCaP human prostate cancer cells
      to examine miR-106b-induced global expression changes among protein-coding genes.
      The approach revealed that CASP7 is a direct target of miR-106b, which was
      confirmed by western blot analysis and a 3'-untranslated region reporter assay.
      Moreover, selected phenotypes induced by miR-106b knockdown in DU145 human
      prostate cancer cells did not develop when both miR-106b and CASP7 expression
      were inhibited. Further analyses showed that CASP7 is downregulated in primary
      prostate tumors and metastatic lesions across multiple data sets and is by itself
      associated with disease recurrence and disease-specific survival. Using
      bioinformatics, we also observed that miR-106b-25 may specifically influence
      focal adhesion-related pathways. This observation was experimentally examined
      using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection
      with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased
      adhesion to basement membrane- and bone matrix-related filaments and enhanced
      soft agar growth. In summary, miR-106b-25 was found to be associated with
      prostate cancer progression and disease outcome and may do so by altering
      apoptosis- and focal adhesion-related pathways.

PMID- 22986526
TI  - The RNA helicase p68 (DDX5) is selectively required for the induction of p53
      dependent p21 expression and cell-cycle arrest after DNA damage.
AB  - The RNA helicase p68 (DDX5) is an established co-activator of the p53 tumour
      suppressor that itself has a pivotal role in orchestrating the cellular response
      to DNA damage. Although several factors influence the biological outcome of p53
      activation, the mechanisms governing the choice between cell-cycle arrest and
      apoptosis remain to be elucidated. In the present study, we show that, while p68
      is critical for p53-mediated transactivation of the cell-cycle arrest gene
      p21(WAF1/CIP1), it is dispensable for induction of several pro-apoptotic genes in
      response to DNA damage. Moreover, p68 depletion results in a striking inhibition
      of recruitment of p53 and RNA Pol II to the p21 promoter but not to the Bax or
      PUMA promoters, providing an explanation for the selective effect on p21
      induction. Importantly, these findings are mirrored in a novel inducible p68
      knockout mouse model in which p68 depletion results in a selective inhibition of
      p21 induction in several tissues. Moreover, in the bone marrow, p68 depletion
      results in an increased sensitivity to gamma-irradiation, consistent with an
      increased level of apoptosis. These data highlight a novel function of p68 as a
      modulator of the decision between p53-mediated growth arrest and apoptosis in
      vitro and in vivo. 

PMID- 22986527
TI  - alpha3beta1 integrins regulate CD151 complex assembly and membrane dynamics in
      carcinoma cells within 3D environments.
AB  - Integrins are extracellular matrix (ECM) receptors that are key players in the
      regulation of tumour cell invasion. The laminin-binding integrin alpha3beta1 has
      previously been shown to regulate adhesion and migration of carcinoma cells in
      part through co-operative signalling with the tetraspanin family of transmembrane
      proteins. However, the spatial and temporal regulation of crosstalk between these
      families of transmembrane proteins in intact cells remains poorly understood.
      Here we have used fluorescence resonance energy transfer (FRET) to demonstrate
      for the first time that alpha3beta1 and the tetraspanin CD151 directly associate
      at the front and retracting rear of polarised migrating breast carcinoma cells in
      both two-dimentional (2D) and three-dimentional (3D)matrices. Furthermore,
      localised alpha3beta1-CD151 binding correlates with lower CD151 homodimerisation
      in cells migrating on laminin or within matrigel. Loss of alpha3beta1 integrin
      leads to increased CD151 homodimer formation, increased activation of Rho GTPase,
      loss of cell polarity and decreased invasion in 3D ECM. As a result, alpha3
      silenced cells show decreased actin-based membrane protrusion and retraction in
      both 2D and 3D environments. These data demonstrate that associations between
      alpha3beta1 and CD151 occur dynamically within discrete subcellular compartments
      and act to establish local GTPase signalling to promote tumour cell invasion.
      These novel findings shed light on the complex crosstalk and switching between
      receptor complexes in response to different extracellular cues during cell
      invasion in 3D environments.

PMID- 22986528
TI  - Depleting IFIT2 mediates atypical PKC signaling to enhance the migration and
      metastatic activity of oral squamous cell carcinoma cells.
AB  - Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) is one of the
      most highly responsive interferon-stimulated genes, but its biological functions
      are poorly understood. In this study, we aimed to explore the underlying
      mechanisms by which depleting IFIT2 induces the migration of oral squamous cell
      carcinoma (OSCC) cells. Stable IFIT2-depleted cells underwent epithelial
      mesenchymal transition (EMT) and exhibited enhanced cell motility and
      invasiveness compared with control cells. Furthermore, our results indicated that
      atypical protein kinase C (aPKC) was activated in IFIT2-depleted cells.
      Inhibition of aPKC using a specific myristoylated PKCzeta pseudosubstrate or aPKC
      targeting small interfering RNA (siRNA) abolished IFIT2 depletion-induced EMT,
      migration and invasion, indicating that the activation of aPKC has an essential
      role in regulating the cellular responses induced by IFIT2 depletion. Following
      tail-vein injection, IFIT2-depleted OSCC cells colonized not only the lungs but
      also the heart, head and neck, retroperitoneal, and peritoneal cavities; whereas
      control cells predominantly localized in the lungs. IFIT2 mRNA and protein
      expression was positively associated with E-cadherin expression in OSCC patient
      specimens. The loss of E-cadherin and IFIT2 expression was observed at the
      invasive front of OSCC tumors, suggesting that the loss of IFIT2 may induce EMT
      and lead to the metastasis of OSCCs. OSCC patients possessing reduced IFIT2
      expression levels (IFIT2 <50%) exhibited greater rates of distant metastasis and
      poor prognoses compared with OSCC patients who expressed greater levels of IFIT2
      (IFIT2 >=50%). These results demonstrate that IFIT2 depletion activates the aPKC
      pathway and consequently induces EMT, cell migration and invasion. Most
      importantly, depleting IFIT2 may participate in OSCC tumor progression,
      particularly during metastasis. Taken together, our study demonstrates that
      IFIT2, a protein responsible for interferon stimulation, may prevent OSCC
      metastasis and serve as a valuable prognostic marker.

PMID- 22986530
TI  - MiR-30a-5p connects EWS-FLI1 and CD99, two major therapeutic targets in Ewing
      tumor.
AB  - Ewing sarcoma is a pediatric bone tumor characterized in 85% of cases by the
      fusion between EWS and FLI1 genes that results in the expression of the EWS-FLI1
      aberrant transcription factor. Histologically, the Ewing tumor expresses high
      levels of the CD99 membrane glycoprotein. It has been recently described that
      CD99 expression contributes to the Ewing tumor oncogenesis by modulating growth
      and differentiation of tumor cells. Different studies have also shown that
      overexpression of EWS-FLI1 induces CD99 expression in non-Ewing cells. At the
      opposite, the knockdown of EWS-FLI1 expression by siRNA approaches has no
      significant effect on CD99 mRNA level in Ewing cells. Here, by in vivo and in
      vitro studies, we show that while EWS-FLI1 inhibition has only slight effects on
      the amount of CD99 transcript, it induces a dramatic decrease of the CD99 protein
      expression level, hence suggesting post-transcriptional regulations, possibly
      mediated by microRNAs. To further investigate this issue, we identified a set of
      91 miRNAs that demonstrate EWS-FLI1 modulation, three of them being predicted to
      bind CD99 3' untranslated region (30'UTR). Among these, we show that miR-30a-5p
      has the ability to interact with the 30'UTR region of CD99 and to regulate its
      expression. Moreover, the re-expression of miRNA-30a-5p in Ewing cell line
      induces decreased cell proliferation and invasion. In this study, we therefore
      show that miR-30a-5p constitutes a major functional link between EWS-FLI1 and
      CD99, two critical biomarkers and therapeutic targets in Ewing sarcoma.

PMID- 22986529
TI  - Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK.
AB  - The proapoptotic BCL-2 family proteins BAX and BAK serve as essential gatekeepers
      of the intrinsic apoptotic pathway and, when activated, transform into pore
      forming homo-oligomers that permeabilize the mitochondrial outer membrane.
      Deletion of Bax and Bak causes marked resistance to death stimuli in a variety of
      cell types. Bax(-/-)Bak(-/-) mice are predominantly non-viable and survivors
      exhibit multiple developmental abnormalities characterized by cellular excess,
      including accumulation of neural progenitor cells in the periventricular,
      hippocampal, cerebellar and olfactory bulb regions of the brain. To explore the
      long-term pathophysiological consequences of BAX/BAK deficiency in a stem cell
      niche, we generated Bak(-/-) mice with conditional deletion of Bax in Nestin
      positive cells. Aged Nestin(Cre)Bax(fl/fl)Bak(-/-) mice manifest progressive
      brain enlargement with a profound accumulation of NeuN- and Sox2-positive neural
      progenitor cells within the subventricular zone (SVZ). One-third of the mice
      develop frank masses comprised of neural progenitors, and in 20% of these cases,
      more aggressive, hypercellular tumors emerged. Unexpectedly, 60% of
      Nestin(Cre)Bax(fl/fl)Bak(-/-) mice harbored high-grade tumors within the testis,
      a peripheral site of Nestin expression. This in vivo model of severe apoptotic
      blockade highlights the constitutive role of BAX/BAK in long-term regulation of
      Nestin-positive progenitor cell pools, with loss of function predisposing to
      adult-onset tumorigenesis.

PMID- 22986531
TI  - Regulation of the tumor suppressor homeogene Cdx2 by HNF4alpha in intestinal
      cancer.
AB  - The gut-specific homeotic transcription factor Cdx2 is a crucial regulator of
      intestinal development and homeostasis, which is downregulated in colorectal
      cancers (CRC) and exhibits a tumor suppressor function in the colon. We have
      previously established that several endodermal transcription factors, including
      HNF4alpha and GATA6, are involved in Cdx2 regulation in the normal gut. Here we
      have studied the role of HNF4alpha in the mechanism of deregulation of Cdx2 in
      colon cancers. Crossing Apc(Delta14/+) mice prone to spontaneous intestinal tumor
      development with pCdx2-9LacZ transgenic mice containing the LacZ reporter under
      the control of the 9.3-kb Cdx2 promoter showed that this promoter segment
      contains sequences recapitulating the decrease of Cdx2 expression in intestinal
      cancers. Immunohistochemistry revealed that HNF4alpha, unlike GATA6, exhibited a
      similar decrease to Cdx2 in genetic (Apc(min/+) and Apc(Delta14/+)) and
      chemically induced (Azoxymethane (AOM) treatment) models of intestinal tumors in
      mice. HNF4alpha and Cdx2 also exhibited a comparable deregulated pattern in human
      CRC. Correlated patterns were observed between HNF4alpha and Cdx2 in several
      experimental models of human colon cancer cell lines: xenografts in nude mice,
      wound healing and glucose starvation. Furthermore, Cdx2 decreased by knocking
      down HNF4alpha in human colon cancer cells using siRNA and in the colon of mice
      conditionally knocked out for the Hnf4alpha gene in the adult intestine
      (Hnf4alpha(f/f);VilCre(ERT2) mice). Finally, the conditionally knocked out mice
      Hnf4alpha(f/f);VilCre(ERT2) treated with the carcinogen AOM developed colorectal
      tumors earlier than wild-type mice, as previously reported for mice with a
      reduced Cdx2 expression. In conclusion, this study provides evidence that the
      downregulation of HNF4alpha is an important determinant of the reduced expression
      of the Cdx2 tumor suppressor gene in intestinal cancers. Consistently, similar to
      Cdx2, HNF4alpha exerts a tumor suppressor function in the colon in that its loss
      of function facilitates tumor progression. 

PMID- 22986532
TI  - Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate
      cancer.
AB  - Integration of cellular signaling pathways with androgen receptor (AR) signaling
      can be achieved through phosphorylation of AR by cellular kinases. However, the
      kinases responsible for phosphorylating the AR at numerous sites and the
      functional consequences of AR phosphorylation are only partially understood.
      Bioinformatic analysis revealed AR serine 213 (S213) as a putative substrate for
      PIM1, a kinase overexpressed in prostate cancer. Therefore, phosphorylation of AR
      serine 213 by PIM1 was examined using a phosphorylation site-specific antibody.
      Wild-type PIM1, but not catalytically inactive PIM1, specifically phosphorylated
      AR but not an AR serine-to-alanine mutant (S213A). In vitro kinase assays
      confirmed that PIM1 can phosphorylate AR S213 in a ligand-independent manner and
      cell type-specific phosphorylation was observed in prostate cancer cell lines.
      Upon PIM1 overexpression, AR phosphorylation was observed in the absence of
      hormone and was further increased in the presence of hormone in LNCaP, LNCaP-abl
      and VCaP cells. Moreover, phosphorylation of AR was reduced in the presence of
      PIM kinase inhibitors. An examination of AR-mediated transcription showed that
      reporter gene activity was reduced in the presence of PIM1 and wild-type AR, but
      not S213A mutant AR. Androgen-mediated transcription of endogenous PSA, Nkx3.1
      and IGFBP5 was also decreased in the presence of PIM1, whereas IL6, cyclin A1 and
      caveolin 2 were increased. Immunohistochemical analysis of prostate cancer tissue
      microarrays showed significant P-AR S213 expression that was associated with
      hormone refractory prostate cancers, likely identifying cells with catalytically
      active PIM1. In addition, prostate cancers expressing a high level of P-AR S213
      were twice as likely to be from biochemically recurrent cancers. Thus, AR
      phosphorylation by PIM1 at S213 impacts gene transcription and is highly
      prevalent in aggressive prostate cancer.

PMID- 22986533
TI  - FAT1 acts as an upstream regulator of oncogenic and inflammatory pathways, via
      PDCD4, in glioma cells.
AB  - Glioblastoma multiforme (GBM) is the most aggressive and the commonest primary
      brain tumor with a tendency for local invasiveness. The pathways of neoplasia,
      invasion and inflammation are inextricably linked in cancer and aberrations in
      several regulatory pathways for these processes have been identified. Here we
      have studied the FAT1 (Homo sapiens FAT tumor-suppressor homolog 1 (Drosophila))
      gene to identify its role in the tumorigenecity of the gliomas. The expression of
      FAT1 was found to be high in grade IV glioma cell lines (U87MG, A172, U373MG and
      T98G) but low in grade III glioma cell lines (GOS3 and SW1088). Two cell lines
      (U87MG and A172) with high FAT1 expression were chosen for in vitro FAT1
      knockdown studies. FAT1 knockdown by small interfering RNA resulted in decreased
      migration and invasion of both the cell lines along with increased expression of
      the tumor-suppressor gene programmed cell death 4 (PDCD4). Increased PDCD4
      expression led to the attenuation of activator protein-1 (AP- 1) transcription by
      inhibiting c-Jun phosphorylation and resulted in concomitant decrease in the
      expression of AP-1-target genes like MMP3, VEGF-C and PLAU, the pro-inflammatory
      regulator COX-2 and cytokines IL1b and IL-6. Conversely, simultaneous silencing
      of PDCD4 and FAT1 in these cells significantly enhanced AP-1 activity and
      expression of its target genes, resulting in increase in mediators of
      inflammation and in enhanced migratory and invasive properties of the cells. We
      also observed a negative correlation between the expression of FAT1 and PDCD4 (P
      = 0.0145), a positive correlation between the expression of FAT1 and COX-2 (P =
      0.048) and a similar positive trend between FAT1 and IL-6 expression in 35
      primary human GBM samples studied. Taken together, this study identifies a novel
      signaling mechanism mediated by FAT1 in regulating the activity of PDCD4 and
      thereby the key transcription factor AP-1, which then affects known mediators of
      neoplasia and inflammation.

PMID- 22986535
TI  - SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency.
AB  - Current genetic evidence in mice indicates that SIRT1 has potent tumor suppressor
      activity in a variety of cancer models, with no evidence yet for SIRT1 oncogenic
      activity in vivo. We report here that transgenic Sirt1 expression is oncogenic in
      murine thyroid and prostate carcinogenesis initiated by Pten-deficiency. Based on
      mRNA expression analyses of pre-tumoral murine thyroids, we find that SIRT1
      increases c-MYC transcriptional programs. Moreover, we show higher c-MYC protein
      levels in murine thyroid cancers from Sirt1 transgenic mice. Similarly, SIRT1 is
      overexpressed in human thyroid cancers and it is positively correlated with c-MYC
      protein levels. Finally, we show in cultured thyroid cancer cells that SIRT1
      stabilizes c-MYC protein. These results implicate SIRT1 as a new candidate target
      for the treatment of thyroid carcinomas.

PMID- 22986534
TI  - Interleukin enhancer-binding factor 3 promotes breast tumor progression by
      regulating sustained urokinase-type plasminogen activator expression.
AB  - Sustained urokinase-type plasminogen activator (uPA) expression is detected in
      aggressive breast tumors. Although uPA can be transiently upregulated by diverse
      extracellular stimuli, sustained, but not transiently upregulated uPA expression
      contributes to breast cancer invasion/metastasis. Unfortunately, how sustained
      uPA expression is achieved in invasive/metastatic breast cancer cells is unknown.
      Here, we show that sustained and transiently upregulated uPA expression are
      regulated by distinct mechanisms. Using a collection of transcription factor
      targeted small-interfering RNAs, we discovered that interleukin enhancer-binding
      factor 3 (ILF3) is required for sustained uPA expression. Two discrete mechanisms
      mediate ILF3 action. The first is that ILF3 activates uPA transcription by
      binding to the CTGTT sequence in the nucleotides -1004~-1000 of the uPA promoter;
      the second is that ILF3 inhibits the processing of uPA mRNA-targeting primary
      microRNAs (pri-miRNAs). Knockdown of ILF3 led to significant reduction in in
      vitro cell growth/migration/invasion and in vivo breast tumor development.
      Importantly, immunohistochemistry (IHC) showed that nuclear ILF3, but not
      cytoplasmic ILF3 staining correlates with elevated uPA level and higher grades of
      human breast tumor specimens. Nuclear localization of ILF3 highlights the role of
      ILF3 in sustained uPA expression as a transcription activator and pri-miRNA
      processing blocker. In conclusion, this study shows that ILF3 promotes breast
      tumorigenicity by regulating sustained uPA expression.

PMID- 22986537
TI  - In vitro selection of peptide aptamers with affinity to single-wall carbon
      nanotubes using a ribosome display.
AB  - A ribosome display from a diverse random library was applied for selecting
      peptide aptamers with high binding affinity to single-wall carbon nanotubes
      (SWCNTs). The selected peptide aptamer bound to and solubilized SWCNTs more
      strongly than did the peptide aptamer selected by a phage display method reported
      previously, and more strongly than other commonly used organic surfactants. The
      fluorescence spectrum of this aptamer showed a red shift upon interaction with
      SWCNTs but circular dichroism spectroscopy did not show any significant
      difference between the presence or absence of SWCNT binding.

PMID- 22986536
TI  - Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic
      cells.
AB  - Hepatocellular carcinoma (HCC) is a malignant tumor and hepatitis B virus X
      protein (HBx) plays a crucial role in its pathogenesis. The Notch1 signaling
      pathway is involved in various malignant tumors including liver cancers and down
      regulation of Notch-1 may exert anti-tumor effects. Here, we demonstrate that
      inhibition of Notch1 by plasmid-based shRNA suppresses growth of human hepatic
      cells transfected with HBx through G0/G1 cell cycle arrest and apoptosis
      inhibition, possibly linked to the promoted expression of cyclin-dependent kinase
      inhibitor, P16, and decreased expression of apoptosis inhibitor, Bcl-2. The anti
      proliferative and pro-apoptotic effects of Notch1 shRNA in HBx-transformed L02
      cell may be partly mediated by down-regulation of nuclear factor-kappaB (NF
      kappaB) binding activities, demonstrating possible cross-talk between Notch-1 and
      NF-kappaB signaling pathways. The oncogene HBx may therefore induce malignant
      transformation of human hepatic cells via Notch1 pathway, indicating that Notch1
      plays a crucial role in HBx-related liver cancer and could be an effective
      therapeutic target for HCC.

PMID- 22986538
TI  - A simple heterogeneous one-step assay for screening estrogenic compounds.
AB  - Estrogen receptor (ER) modulators are a serious health issue but estrogenic
      compounds, especially antagonists of ER function, are widely screened for in
      search of novel therapeutics against hormonal diseases such as the breast cancer.
      Here we report a novel and a simple bioassay for estrogenic and anti-estrogenic
      compounds based on ligand-dependent recruitment of ER co-activator steroid
      receptor co-activator 1 (SRC-1) to purified Renilla luciferase-tagged ERalpha. In
      this assay, in vivo-biotinylated (E. coli) SRC-1, purified Renilla luciferase
      ERalpha, and the analyte sample are mixed and incubated for 2 h in a streptavidin
      coated microtiter wells, and after one washing step, luminescence is measured
      with a simple instrument. The assay does not require chemical labeling of the
      components and shows good sensitivity (25 pM E(2)) and wide dynamic range of more
      than four orders of magnitude.

PMID- 22986539
TI  - Microbial transformation of 20(S)-protopanaxatriol by Absidia corymbifera and
      their cytotoxic activities against two human prostate cancer cell lines.
AB  - Seven hydroxylates of 20(S)-protopanaxatriol (1) transformed by Absidia
      corymbifera AS 3.3387 were isolated and identified by spectral methods including
      2D-NMR. Among them, 7beta-hydroxyl-20(S)-protopanaxatriol (2), 7alpha-hydroxyl
      20(S)-protopanaxatriol (3), and 7beta, 15alpha-dihydroxyl-20(S)-protopanaxatriol
      (7) are new compounds. The metabolites 2, 6, 7, and 8 showed the more potent
      inhibitory effects against DU-145 and PC-3 cell lines than the substrate.

PMID- 22986540
TI  - Aortic valve closure for rapidly deteriorated aortic insufficiency after
      continuous flow left ventricular assist device implantation.
AB  - A patient underwent aortic valve closure for de novo aortic insufficiency that
      had deteriorated to severe insufficiency during six months of support with a
      continuous flow left ventricular assist device (cf-LVAD). Aortic insufficiency
      was initially noted one month after LVAD implantation, and then deterioration
      quickly developed. Right heart catheterization revealed that when the rotational
      speed of the cf-LVAD was increased, the cardiac index was decreased by an
      increase in regurgitant volume, as shown by echocardiography. During surgery,
      fusion and shortening of the aortic leaflets as well as left coronary ostial
      occlusion were observed. Direct aortic closure improved hemodynamics. Thrombus
      formation on the aortic valve shown by echocardiography in the early
      postoperative period may be a trigger of aortic insufficiency. Control of the cf
      LVAD rotational speed is likely required to prevent aortic insufficiency.

PMID- 22986541
TI  - [HIV test and prevention].
AB  - Successful prevention of an HIV epidemic is still a desirable goal. As young
      people are mainly affected by new infections and AIDS mortality has fallen
      virtually to zero, the long-term total costs of HIV management are increasing.
      This report describes how the targeted application of HIV testing can influence
      the HIV epidemic. The crucial point is the early diagnosis of primary HIV
      infection in standard situations whereby early diagnosis and counselling result
      in behavioral modifications preventing new transmission.

PMID- 22986542
TI  - [HIV infection : chronic disease with comorbidities].
AB  - While HIV therapy is highly efficient comorbidities come into the focus of HIV
      long-term treatment and prognosis. The pathogenesis of many comorbid diseases is
      determined not only by the biological effects of the HIV infection itself but
      also by lifestyle and long-term adverse reactions of antiviral treatment. The HIV
      specialist should nowadays be an all-round internist or needs a good
      infrastructure of cooperation. Cardiovascular risk factors in HIV infection
      include serum lipids, especially high LDL levels under antiviral treatment. They
      can be managed either by a switch of HIV therapy of by the addition of lipid
      lowering agents. However, smoking habits and normalization of high blood pressure
      are also of importance. Further important comorbidities present in patients are
      viral hepatitis B or C, nephropathy (HIV or secondary) and changes of bone
      turnover resulting in lower bone mass and stability. Other aspects include
      vaccination status and prevention also for non-HIV associated carcinomas.

PMID- 22986543
TI  - [Dronedarone in high-risk patients with atrial fibrillation :  PALLAS study].

PMID- 22986544
TI  - Suggestion of end points of complete keloid excision.

PMID- 22986545
TI  - Plastic surgery training: evaluating patient satisfaction with facial fillers in
      a resident clinic.
AB  - BACKGROUND: Resident cosmetic surgery clinics, or "chief clinics," are arguably
      the most effective way to provide cosmetic surgery training. Approximately 70 %
      of plastic surgery training programs utilize a "chief resident clinic" to augment
      their cosmetic surgery experience, even though a quantitative outcome scale is
      lacking to guide education. We report the use of the FACE-Q, a novel patient
      outcome tool, to evaluate patients' satisfaction with nonsurgical facial
      rejuvenation performed by residents. METHODS: The FACE-Q "Satisfaction with
      Facial Appearance Overall Scale" was administered to patients prior to and 1 week
      after undergoing nonsurgical facial rejuvenation performed by plastic surgery
      residents. All patients received nonsurgical facial rejuvenation with botulinum
      toxin A and hyaluronic acid as part of resident facial aesthetics training.
      RESULTS: Eleven patients completed the pre- and postinjection FACE-Q survey.
      Average overall facial appearance satisfaction scores of 47.6 pre- and 51.1
      postinjection were found (p < 0.037), with a total possible score of 68. Ten
      patients (91 %) reported feeling satisfied or very satisfied with the overall
      appearance of their face following injection. CONCLUSION: Despite resident
      inexperience and patient awareness that novices were performing the procedures,
      our experience supports use of the FACE-Q to optimize and endorse resident
      cosmetic surgery clinics. The learning curve for facial cosmetic procedures can
      be adversely affected by limited time available or exposure to improvement
      variables when initially performing the procedure. It is imperative to any
      technique that direct, and preferably quantitative, feedback is given so that an
      immediate modification can be generated and successive patient outcomes improved.
      LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 22986546
TI  - Sex, mutations and marketing. How the Cambrian explosion set the stage for
      runaway consumerism.

PMID- 22986548
TI  - Equally potent? Does cellular reprogramming justify the abandonment of human
      embryonic stem cells?

PMID- 22986547
TI  - Open and closed domains in the mouse genome are configured as 10-nm chromatin
      fibres.
AB  - The mammalian genome is compacted to fit within the confines of the cell nucleus.
      DNA is wrapped around nucleosomes, forming the classic "beads-on-a-string" 10-nm
      chromatin fibre. Ten-nanometre chromatin fibres are thought to condense into 30
      nm fibres. This structural reorganization is widely assumed to correspond to
      transitions between active and repressed chromatin, thereby representing a chief
      regulatory event. Here, by combining electron spectroscopic imaging with
      tomography, three-dimensional images are generated, revealing that both open and
      closed chromatin domains in mouse somatic cells comprise 10-nm fibres. These
      findings indicate that the 30-nm chromatin model does not reflect the true
      regulatory structure in vivo.

PMID- 22986549
TI  - More than meets the eye. Modern experimental techniques require increasingly
      sophisticated approaches to data visualization.

PMID- 22986551
TI  - Everybody wins! Poland hosts thrilling competitions of viruses, RNAi and football
      teams.
AB  - The ESF-EMBO conference on 'Antiviral RNAi: From Molecular Biology towards
      Applications' took place in June 2012 in Pultusk, Poland. It brought together
      scientists working at the interface of RNAi and virus infections in different
      organisms, covering the complete range from basic mechanisms of RNA silencing to
      RNAi-based antiviral therapy.

PMID- 22986552
TI  - Searching for the Holy Grail; protein-protein interaction analysis and
      modulation.
AB  - The first EMBO workshop on 'Protein-Protein Interaction Analysis & Modulation'
      took place in June 2012 in Roscoff, France. It brought together researchers to
      discuss the growing field of protein network analysis and the modulation of
      protein-protein interactions, as well as outstanding related issues including the
      daunting challenge of integrating interactomes in systems biology and in the
      modelling of signalling networks.

PMID- 22986553
TI  - The postmodern assault on science. If all truths are equal, who cares what
      science has to say?

PMID- 22986554
TI  - Serum chitotriosidase activity in acute coronary syndrome.
AB  - AIM: Inflammation is a critical participant in mediating all stages of
      cardiovascular disease. Studies related with chitotriosidase that was recently
      found to be relevant to arterial inflammation. In this study we evaluated
      activity of serum chitotriosidase in acute coronary syndrome patients and its
      relationship with cardiovascular events, cardiac enzymes and inflammatory
      indicators. METHODS: We prospectively analyzed consecutive 30 patients with ST
      segment elevation myocardial infarction, 30 patients with non ST-segment
      elevation myocardial infarction, 30 patients with unstable angina pectroris who
      were admitted to our intensive care unit and 30 healthy people (average age
      56.86+/-10.44 years, 81 male) between Jaunary and June 2010. Details of baseline
      clinical characteristics, biochemical values, receiving treatment and basal ECG
      findings were recorded. Data of patients with coronary angiography were
      evaluated. RESULTS: Cut off value of chitotriosidase was calculated 82.00 mmol.ml
      1.h-1, with 83 percent sensitivity and 72 percent spesificity. The activity of
      chitotriosidase in acute coronary syndrome group was 88.85+/-23.08 mmol.ml-1 .h
      1, where as the control group was 68.47+/-28.44 mmol.ml-1.h-1, respectively
      p=0.001).The highest activity of chitotriosidase (96.11+/-19.77 mmol.ml-1.h-1)
      was found in ST-segment elevation myocardial infarction group and the minimal
      activity of chitotriosidase was in the control group (68.47+/-28.44 mmol.ml-1.h
      1) (p= 0.001). The activity of chitotriosidase in ST-segment elevation myocardial
      infarction and non ST-segment elevation myocardial infarction groups were
      significantly higher than control group (p=0.001 and p=0.045). When acute
      coronary syndrome groups compared to control; a positive correlation was found
      between chitotriosidase activity and hs-CRP (r=0.21, p= 0.046), troponin T
      (r=0.25, p=0.016), creatine kinase-MB (r=0.20, p=0.059). CONCLUSION: The activity
      of chitotriosidase is increased in acute coronary syndrome patients.
      Chitotriosidase is higher in ST-segment elevation myocardial infaction group than
      non ST-segment elevation myocardial infarction and unstable angina pectoris
      group.

PMID- 22986555
TI  - Left ventricular thrombus and subsequent thromboembolism, comparison of
      anticoagulation, surgical removal, and antiplatelet agents.
AB  - Left ventricular (LV) thrombus is one of the risk factors for systemic
      thromboembolism. The aims of this study were to compare the long-term clinical
      outcomes of LV thrombus using current therapeutics, anticoagulation, operative
      treatment, and antiplatelet agents and to identify independent predictors of
      systemic thromboembolism. METHODS: We screened 86,374 patients for intracardiac
      thrombus in the electronic medical records and imaging databases. Records of 62
      patients with LV thrombus, diagnosed between May 2003 to November 2011, were
      comprehensively reviewed regarding baseline characteristics, imaging data and
      thrombus outcomes, thromboembolic events and treatment complications by treatment
      group. RESULTS: The majority (80.6%) had ischemic etiology. Systemic
      thromboembolism developed in 18 patients; 8 (45%) were post-treatment
      thromboembolisms while 10 events occurred before treatment began. No post
      treatment thromboembolism occurred in the operative treatment group; in contrast,
      7 post-treatment thromboembolisms occurred in anticoagulation group (17%) (Log
      rank p= 0.175). Independent predictors of post-treatment thromboembolism were
      dilated cardiomyopathy (HR 61.30, p= 0.001), previous cerebrovascular events (HR
      7.06, p= 0.042), female gender (HR 7.11, p= 0.031), and echocardiographic left
      ventricular end-diastolic diameter (HR 1.15, p= 0.047). CONCLUSIONS: In this
      study, the rate of post-treatment thromboembolism was not significantly different
      among the treatment groups; however, operative treatment tended towards less post
      treatment thromboembolism than other treatment groups.

PMID- 22986556
TI  - Healthcare policy. Editorial.

PMID- 22986557
TI  - Confessions of an MBA grad: life in the real world.

PMID- 22986558
TI  - Old school thinking not the answer to economic growth.

PMID- 22986560
TI  - All-cause readmission to acute care for cancer patients.
AB  - A recent Canadian Institute for Health Information report on all-cause
      readmission identified that cancer patients had higher-than-average readmission
      rates. This study provides further insight on the experience of cancer patients,
      exploring the risk factors associated with readmission at patient, hospital and
      community levels. An analysis showed that patient characteristics, including the
      reason for initial hospitalization, sex, co-morbidity levels, admission through
      the emergency department and the number of previous acute care admissions, were
      associated with readmission for cancer patients. In addition, we found that the
      readmission rate for these patients varied by hospital size and whether the
      patients lived in rural or urban locations.

PMID- 22986561
TI  - All the right intentions but few of the desired results: lessons on access to
      primary care from Ontario's patient enrolment models.

PMID- 22986562
TI  - In conversation with David Levine. Interview by Ken Tremblay.

PMID- 22986563
TI  - Ethical framework for resource allocation during a drug supply shortage.
AB  - Drug supply shortages are common in health systems due to manufacturing and other
      delays. Frequently, shortages are successfully addressed through conservation and
      redistribution efforts, with limited impact on patient care. However, when Sandoz
      Canada Inc. announced in February 2012 that it was reducing production of a
      number of generic injectable drugs at its Quebec facility, the scope and
      magnitude of the drug supply shortage were unprecedented in Canada. The potential
      for an extreme scarcity of some drugs raised ethical concerns about patient care,
      including the need to limit access to some health services. In this article, the
      authors describe the development and implementation of an ethical framework to
      promote equitable access to drugs and healthcare services in the context of a
      drug supply shortage within and across health systems.

PMID- 22986564
TI  - Voluntary versus involuntary waiting for joint replacements: new Alberta wait
      times rules for hip and knee arthroplasties, with provincial consensus.
AB  - Despite various health system improvements across Alberta, the wait times
      benchmark was not being met for all patients requiring hip or knee arthroplasty.
      Alberta Health Services Bone and Joint Clinical Network working groups, in
      collaboration with other provincial organizations, gained consensus on the
      development and implementation of a set of provincial Wait Times Rules. These
      rules standardize the definition and measurement of data elements specific to
      joint replacement and distinguish between voluntary (patient-related) versus
      involuntary (healthcare system-related) wait times. Collectively, this
      information will help identify trends in wait times and more accurately show
      where wait times can be reduced.

PMID- 22986565
TI  - Sustaining walk-in counselling services: an economic assessment from a pilot
      study.
AB  - Introducing single-session walk-in counselling services in a counselling agency
      virtually eliminated a lengthy wait list and reduced costly no-shows for
      scheduled counselling. A pilot study found that client distress decreased
      significantly following the single session, and a high proportion of clients were
      "ready for change." The service diverts clients from using hospitals and family
      doctors/walk-in clinics and toward using community social services. It also
      enables an earlier return to work and usual activities. The social benefits
      (reduced hospital use and faster return to work) exceed the cost of the service.
      This information is helping to make the case for sustaining and expanding these
      services.

PMID- 22986566
TI  - Developing a physician engagement agreement at The Ottawa Hospital: a
      collaborative approach.
AB  - The Ottawa Hospital (TOH) is focused on providing safe, high-quality care to its
      patients. TOH has identified physician engagement as a critical factor for
      improving the quality of care they provide. The physician engagement strategy
      developed at TOH involved a qualitative inquiry into the impediments and
      facilitators of engagement. Using concurrent focus groups, researchers collected
      and analyzed the physicians' perspective regarding engagement. A systematic
      analysis of the verbal data was used to construct a statement of mutual
      understanding between the physicians and the hospital (physician engagement
      agreement). The process of developing this agreement is the focus of this
      article.

PMID- 22986567
TI  - Engaging instincts to improve leadership performance: a case study.

PMID- 22986568
TI  - Patient satisfaction after the redesign of a chemotherapy booking process.

PMID- 22986569
TI  - Collateral impact of a hospital outbreak of Clostridium difficile: an
      unrecognized surge event requiring a system-level response.
AB  - This paper discusses a unique surge event caused by an outbreak of Clostridium
      difficile, resulting not from an increase in the demands on the healthcare system
      but, rather, from a substantial decrease in the capacity to provide care when the
      medical capacity in the facility was decreased by 50% due to bed closures.
      Approaches to managing the situation using the staff, stuff and space paradigm
      are presented as strategies to prevent future adverse medical events.

PMID- 22986572
TI  - Rare-earth metal complexes having an unusual indolyl-1,2-dianion through C-H
      activation with a novel eta1:(MU2-eta1:eta1) bonding with metals.
AB  - Studies on the reactions of 3-(tert-butyliminomethine)indole or 3-(tert
      butylaminomethylene)indole with rare-earth metal amides
      [(Me(3)Si)(2)N](3)RE(III)(MU-Cl)Li(THF)(3) (RE = Y, Yb) led to the discovery of
      different reactivity patterns with isolation of novel rare-earth metal complexes
      having a unique indolyl-1,2-dianion in a novel eta(1):(MU(2)-eta(1):eta(1))
      bonding mode through C-H activation.

PMID- 22986573
TI  - Establishment of a normative pediatric acoustic database.
AB  - OBJECTIVES To establish a normative pediatric acoustic database and to analyze
      the acoustic characteristics of the age groups studied. DESIGN Prospective
      gathering of acoustic parameters on healthy children aged 4 to 18 years. SETTING
      An outpatient pediatric otolaryngology clinic. PATIENTS A total of 335 children
      (165 girls and 170 boys) were evaluated. MAIN OUTCOME MEASURES Normative values
      were obtained for the acoustic parameters studied. RESULTS Discrete fundamental
      frequency changes occurred at ages 11 and 14 years in girls and ages 12 and 16
      years in boys. Values for jitter percentage, shimmer percentage, and noise to
      harmonic ratio fell within the normative thresholds of adult values. CONCLUSIONS
      This is the largest pediatric computerized voice analysis database in the English
      language. This database has been designed to develop an age- and sex-based growth
      chart to track the developing pediatric voice as it changes with maturation. A
      distinct vocal profile of girls and boys is evident, with key changes noted at
      critical periods of development and with significant differences among
      fundamental frequency between and within sexes. A comprehensive database can be
      used to help aid future voice therapy and phonosurgical strategies and provide
      the foundation for future studies into the development of the pediatric voice as
      it matures into adulthood.

PMID- 22986574
TI  - Assessing spatial variability of soil petroleum contamination using visible near
      infrared diffuse reflectance spectroscopy.
AB  - Visible near-infrared (VisNIR) diffuse reflectance spectroscopy (DRS) is a rapid,
      non-destructive method for sensing the presence and amount of total petroleum
      hydrocarbon (TPH) contamination in soil. This study demonstrates the feasibility
      of VisNIR DRS to be used in the field to proximally sense and then map the areal
      extent of TPH contamination in soil. More specifically, we evaluated whether a
      combination of two methods, penalized spline regression and geostatistics could
      provide an efficient approach to assess spatial variability of soil TPH using
      VisNIR DRS data from soils collected from an 80 ha crude oil spill in central
      Louisiana, USA. Initially, a penalized spline model was calibrated to predict TPH
      contamination in soil by combining lab TPH values of 46 contaminated and
      uncontaminated soil samples and the first-derivative of VisNIR reflectance
      spectra of these samples. The r(2), RMSE, and bias of the calibrated penalized
      spline model were 0.81, 0.289 log(10) mg kg(-1), and 0.010 log(10) mg kg(-1),
      respectively. Subsequently, the penalized spline model was used to predict soil
      TPH content for 128 soil samples collected over the 80 ha study site. When
      assessed with a randomly chosen validation subset (n = 10) from the 128 samples,
      the penalized spline model performed satisfactorily (r(2) = 0.70; residual
      prediction deviation = 2.0). The same validation subset was used to assess point
      kriging interpolation after the remaining 118 predictions were used to produce an
      experimental semivariogram and map. The experimental semivariogram was fitted
      with an exponential model which revealed strong spatial dependence among soil TPH
      [r(2) = 0.76, nugget = 0.001 (log(10) mg kg(-1))(2), and sill 1.044 (log(10) mg
      kg(-1))(2)]. Kriging interpolation adequately interpolated TPH with r(2) and RMSE
      values of 0.88 and 0.312 log(10) mg kg(-1), respectively. Furthermore, in the
      kriged map, TPH distribution matched with the expected TPH variability of the
      study site. Since the combined use of VisNIR prediction and geostatistics was
      promising to identify the spatial patterns of TPH contamination in soils, future
      research is warranted to evaluate the approach for mapping spatial variability of
      petroleum contaminated soils.

PMID- 22986575
TI  - [Dose reduction and adequate image quality in digital radiography: a
      contradiction?].
AB  - CLINICAL/METHODICAL ISSUE: Dose reduction and adequate image quality in digital
      radiography - a contradiction? STANDARD RADIOLOGICAL METHODS: Digital radiography
      has already replaced traditional screen-film systems. METHODICAL INNOVATIONS:
      Substantial improvements in both dose efficiency and spatial resolution
      demonstrate the rapid developments in digital radiography. PERFORMANCE: Needle
      detector systems have shown up to a 50% dose reduction compared to traditional
      screen-film systems. There is also a dose reduction capability of up to 50%
      comparing direct radiography (DR) systems to computed radiography (CR) systems
      for chest X-rays. However, despite the most recent achievements of CR technology,
      the dose efficiency of DR systems (caesium iodide flat-panel detector) is
      unparalleled. ACHIEVEMENTS: The progress in detector technology has contributed
      to dose reduction and improved image quality, while saving time and providing a
      higher examination rate. PRACTICAL RECOMMENDATIONS: The use of dose indicators
      and longitudinal dose control are important to avoid substantial accidental dose
      increase. The dose applied to patients should fall markedly below the defined
      diagnostic reference levels within the European Union. Regular quality control,
      as well as continuous education and training of medical and technical personnel,
      contribute to ensure that the ALARA (as low as reasonably achievable) principle
      is consistently followed.

PMID- 22986576
TI  - [Dose optimization in CT examination of children].
AB  - CLINICAL/METHODICAL ISSUE: Problems arise due to the increased clinical use of
      computed tomography (CT) and the high radiosensitivity of children. STANDARD
      RADIOLOGICAL METHODS: The ALARA concept (as low as reasonably achievable)
      prevails in pediatric radiology. METHODICAL INNOVATIONS: Justified indications
      and full utilization of available dose optimization methods. PERFORMANCE: Medical
      physicists and the manufacturers should support pediatric radiology in the
      implementation of the ALARA concept. ACHIEVEMENTS: The referring physicians and
      radiology staff should be integrated into training programs. PRACTICAL
      RECOMMENDATIONS: Sufficient diagnostic image quality is paramount and not the
      pretty images.

PMID- 22986577
TI  - Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis
      inducing ligand through induction of reactive oxygen species in prostate cancer
      cells.
AB  - BACKGROUND: Effective treatment of prostate cancer (PCa) remains a major
      challenge due to chemoresistance to drugs including tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL). Ethanol and ethanol extracts are known
      apoptosis inducers. However, cytotoxic effects of ethanol on PCa cells are
      unclear. METHODS: In this study we utilized PC3 and LNCaP cell culture models. We
      used immunohistochemical analysis, western blot analysis, reactive oxygen species
      (ROS) measurement, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) Cell Proliferation Assay, Annexin-V staining and flow cytometry for
      quantification of apoptosis. In vitro soft agar colony formation and Boyden
      chamber invasion assays were used. Tumorigenicity was measured in a
      xenotransplantation mouse model. RESULTS: Here, we demonstrate that ethanol
      enhances the apoptosis-inducing potential of TRAIL in androgen-resistant PC3
      cells and sensitizes TRAIL-resistant, androgen sensitive LNCaP cells to apoptosis
      through caspase activation, and a complete cleavage of poly (ADP)-ribose
      polymerase, which was in association with increased production of ROS. The
      cytotoxicity of ethanol was suppressed by an antioxidant N-acetyl cystein
      pretreatment. Furthermore, ethanol in combination with TRAIL increased the
      expression of cyclin-dependent kinase inhibitor p21 and decreased the levels of
      Bcl-2 and phosphorylated-AKT. These molecular changes were accompanied by
      decreased proliferation, anchorage-independent growth and invasive potential of
      PC3 and LNCaP cells. In vivo studies using a xenotransplantation mouse model with
      PC3 cells demonstrated significantly increased apoptosis in tumors treated with
      ethanol and TRAIL in combination. CONCLUSIONS: Taken together, use of ethanol in
      combination with TRAIL may be an effective strategy to augment sensitivity to
      TRAIL-induced apoptosis in PCa cells.

PMID- 22986578
TI  - A meta-analysis of efficacy and safety of the new alpha1A-adrenoceptor-selective
      antagonist silodosin for treating lower urinary tract symptoms associated with
      BPH.
AB  - BACKGROUND: Recently several clinical trials have focused on the efficacy and
      safety of silodosin, a new, highly selective alpha1A-blocker. We tried to verify
      silodosin's superiority to placebo and non-inferiority to tamsulosin in treating
      patients with lower urinary tract symptoms (LUTS) associated with BPH. METHODS:
      All randomized placebo- and active- controlled trials with silodosin were
      included systematically using Medline, Embase and The Cochrane Library. Primary
      outcome was International Prostate Symptom Score (IPSS) and IPSS subsores;
      secondary outcomes were peak urinary flow rate (Q(max)), quality of life (QoL)
      and primary adverse events (AEs) included retrograde ejaculation, dizziness and
      headache. RESULTS: The data of the included randomized controlled trials (RCTs)
      were collected, extracted, and assessed by our protocol. Five RCTs including a
      total of 2595 patients were identified. Meta-analysis indicated that silodosin
      achieved significant improvement versus placebo in total IPSS, in IPSS subscores,
      and in Q(max); silodosin showed a greater improvement in voiding symptoms than
      tamsulosin, and a higher incidence of retrograde ejaculation than placebo and
      tamsulosin. No significant differences were observed in total IPSS, in IPSS
      storage symptoms, in Q(max) and in QoL when compared with tamsulosin. Silodosin
      was associated with the same low incidence of dizziness and headache with placebo
      and tamsulosin. CONCLUSIONS: Silodosin is an effective and well-tolerated
      treatment for both voiding and storage symptoms in patients with LUTS associated
      with BPH. Despite with increased retrograde ejaculation, its overall efficacy is
      not inferior to tamsulosin, while at the same time being possibly superior to
      tamsulosin.

PMID- 22986579
TI  - Ocular rhinosporidiosis presenting as recurrent chalazion.
AB  - Rhinosporidiosis, a granulomatous disease caused by Rhinosporidium seeberi, is
      widely prevalent in Sri Lanka and southern parts of India. Besides the eye, the
      lacrimal passage and nasal cavity are affected. The most common ocular
      involvement is a subconjunctival bleeding mass. Our case, a 9-year-old girl from
      a rural background with a history of pond water bathing, presented with a
      marginal chalazion involving the left lower lid. She had a history of chalazion
      involving the same site three months earlier which was managed by incision and
      curettage. A decision of surgical exploration was made and the evacuated mass was
      examined histologically showing evidence of rhinosporidiosis. This type of
      clinical presentation for ocular rhinosporidiosis (as recurrent chalazion) has
      not been reported earlier in the literature. This case emphasises that the
      clinicians from this part of the world must consider ocular rhinosporidiosis as
      differential diagnosis in cases with recurrent chalazion especially in a rural
      background with a habit of pond water bathing. 

PMID- 22986580
TI  - Granulomatous uveitis and reactive arthritis as manifestations of post
      streptococcal syndrome.
AB  - To report a case of bilateral granulomatous post-streptococcal syndrome uveitis
      in association with reactive arthritis as manifestation of post-streptococcal
      syndrome. To our knowledge, this could represent the first reported case in the
      literature. A 9-year-old girl, with no past ocular history, presented with a 5
      day history of bilateral blurred vision, red eyes, photophobia and walking
      difficulties because of a right ankle pain. Ophthalmic examination disclosed a
      visual acuity limited to hand motion, mutton-fat keratic precipitates, anterior
      chamber cells and posterior synechiae in both eyes. Ocular pressure was normal.
      Physical examination showed a fever (38  degrees C), inflammatory ankle arthritis
      and scarlet fever (streptococcal lesion). Anti-streptococcal lysine O titer was
      419 MU/ml. The patient was treated with topical steroids, cycloplegics, high-dose
      oral steroids and preventive course of penicillin with total improvement and no
      recurrence. Post-streptococcal syndrome should be considered in the etiology of
      acute bilateral granulomatous uveitis in children, and anti-streptococcal lysine
      O titer should be considered in serodiagnostic testing. 

PMID- 22986581
TI  - Alu-Alu fusion sequences identified at junction sites of copy number amplified
      regions in cancer cell lines.
AB  - Alu elements are short, ~300-bp stretches of DNA and are the most abundant
      repetitive elements in the human genome. A large number of chromosomal
      rearrangements mediated by Alu-Alu recombination have been reported in germline
      cells, but only a few in somatic cells. Cancer development is frequently
      accompanied by various chromosomal rearrangements including gene amplification.
      To explore an involvement of Alu-Alu fusion in gene amplification events, we
      determined 20 junction site sequences of 5 highly amplified regions in 4 cancer
      cell lines. The amplified regions exhibited a common copy number profile: a stair
      like increase with multiple segments, which is implicated in the breakage-fusion
      bridge (BFB) cycle-mediated amplification. All of the sequences determined were
      characterized as head-to-head or tail-to-tail fusion of sequences separated by 1
      5 kb in the genome sequence. Of these, 4 junction site sequences were identified
      as Alu-Alu fusions between inverted, paired Alu elements with relatively long
      overlapping sequences of 17, 21, 22, and 24 bp. Together with genome mapping data
      of Alu elements, these findings suggest that when breakages occur at or near
      inverted, paired Alu elements in the process of BFB cycle-mediated amplification,
      sequence homology of Alu elements is frequently used to repair the broken ends.

PMID- 22986582
TI  - Dopaminergic degeneration is enhanced by chronic brain hypoperfusion and
      inhibited by angiotensin receptor blockage.
AB  - The possible interaction between brain hypoperfusion related to aging and/or
      vascular disease, vascular parkinsonism and Parkinson's disease, as well as the
      possible contribution of aging-related chronic brain hypoperfusion in the
      development or severity of Parkinson's disease are largely unknown. We used a rat
      model of chronic cerebral hypoperfusion to study the long-term effects of
      hypoperfusion on dopaminergic neurons and the possible synergistic effects
      between chronic hypoperfusion and factors that are deleterious to dopaminergic
      neurons, such as the dopaminergic neurotoxin 6-hydroxydopamine. Chronic
      hypoperfusion induced significant loss of dopaminergic neurons and striatal
      dopaminergic terminals and a reduction in striatal dopamine levels. Furthermore,
      intrastriatal administration of 6-hydroxydopamine in rats subjected to chronic
      hypoperfusion induced a significantly greater loss of dopaminergic neurons than
      in sham-operated control rats. The dopaminergic neuron loss was significantly
      reduced by oral treatment with angiotensin type 1 receptor antagonist candesartan
      (3 mg/kg/day). The levels of angiotensin type 2 receptors were lower and the
      levels of angiotensin type 1 receptors, interleukin-1 beta and nicotinamide
      adenine dinucleotide phosphate oxidase activity were higher in the substantia
      nigra of rats subjected to chronic hypoperfusion than in control rats; this was
      significantly reduced by treatment with candesartan. The results suggest that
      early treatment of vascular disease should be considered in the treatment of aged
      Parkinson's disease patients and Parkinson's disease patients with
      cerebrovascular risk factors. The findings also suggest that inhibition of brain
      renin-angiotensin activity may be useful as a neuroprotective strategy.

PMID- 22986584
TI  - Removal of tattoos by q-switched laser: variables influencing outcome and
      sequelae in a large cohort of treated patients.
AB  - OBJECTIVE To analyze variables affecting the treatment course and prognosis of Q
      switched laser tattoo removal. DESIGN Observational prospective cohort study.
      SETTING The study was carried out in a referral center for surgery and laser
      surgery in Milan. PARTICIPANTS Of 397 consecutive patients initially enrolled
      from January 1, 1995, to December 31, 2010, 352 patients (201 men and 151 women;
      median age, 30 years) were included in the analysis. INTERVENTION All patients
      were treated by the same investigator with Q-switched 1064/532-nm Nd:YAG laser
      and Q-switched 755-nm alexandrite laser according to tattoo colors. Laser
      sessions were scheduled at 6-week or longer intervals. MAIN OUTCOME MEASURES
      Successful therapy was defined as removal of the tattoo, with no adverse effects
      other than transient hypochromia or darkening. RESULTS The cumulative rates of
      patients with successful tattoo removal were 47.2% (95% CI, 41.8%-52.5%) after 10
      sessions and 74.8% (95% CI, 68.9%-80.7%) after 15 sessions. Smoking, the presence
      of colors other than black and red, a tattoo larger than 30 cm2, a tattoo located
      on the feet or legs or older than 36 months, high color density, treatment
      intervals of 8 weeks or less, and development of a darkening phenomenon were
      associated with a reduced clinical response to treatment. CONCLUSIONS To our
      knowledge, this study is the first to formally assess prognostic factors for
      effective tattoo removal by Q-switched laser. Several variables influence
      response rates and should be considered when planning tattoo removal treatments.

PMID- 22986583
TI  - Association of healthy aging with parental longevity.
AB  - Various measures incorporated in geriatric assessment have found their way into
      frailty indices (FIs), which have been used as indicators of survival/mortality
      and longevity. Our goal is to understand the genetic basis of healthy aging to
      enhance its evidence base and utility. We constructed a FI as a quantitative
      measure of healthy aging and examined its characteristics and potential for
      genetic analyses. Two groups were selected from two separate studies. One group
      (OLLP for offspring of long-lived parents) consisted of unrelated participants at
      least one of whose parents was age 90 or older, and the other group of unrelated
      participants (OSLP for offspring of short-lived parents), both of whose parents
      died before age 76. FI34 scores were computed from 34 common health variables and
      compared between the two groups. The FI34 was better correlated than
      chronological age with mortality. The mean FI34 value of the OSLP was 31 % higher
      than that of the OLLP (P = 0.0034). The FI34 increased exponentially, at an
      instantaneous rate that accelerated 2.0 % annually in the OLLP (P = 0.024) and
      2.7 % in the OSLP (P < < 0.0001) consequently yielding a 63 % larger accumulation
      in the latter group (P = 0.0002). The results suggest that accumulation of health
      deficiencies over the life course is not the same in the two groups, likely due
      to inheritance related to parental longevity. Consistent with this, sib pairs
      were significantly correlated regarding FI34 scores, and heritability of the FI34
      was estimated to be 0.39. Finally, hierarchical clustering suggests that the OLLP
      and OSLP differ in their aging patterns. Variation in the FI34 is, in part, due
      to genetic variation; thus, the FI34 can be a phenotypic measure suitable for
      genetic analyses of healthy aging.

PMID- 22986585
TI  - Soil changes induced by rubber and tea plantation establishment: comparison with
      tropical rain forest soil in Xishuangbanna, SW China.
AB  - Over the past thirty years, Xishuangbanna in Southwestern China has seen dramatic
      changes in land use where large areas of tropical forest and fallow land have
      been converted to rubber and tea plantations. In this study we evaluated the
      effects of land use and slope on soil properties in seven common disturbed and
      undisturbed land-types. Results indicated that all soils were acidic, with pH
      values significantly higher in the 3- and 28-year-old rubber plantations. The
      tropical forests had the lowest bulk densities, especially significantly lower
      from the top 10 cm of soil, and highest soil organic matter concentrations. Soil
      moisture content at topsoil was highest in the mature rubber plantation. Soils in
      the tropical forests and abandoned cultivated land had inorganic N (IN)
      concentrations approximately equal in NH(4) (+)-N and NO(3) (-)-N. However, soil
      IN pools were dominated by NH(4) (+)-N in the rubber and tea plantations. This
      trend suggests that conversion of tropical forest to rubber and tea plantations
      increases NH(4) (+)-N concentration and decreases NO(3) (-)-N concentration, with
      the most pronounced effect in plantations that are more frequently fertilized.
      Soil moisture content, IN, NH(4) (+)-N and NO(3) (-)-N concentrations within all
      sites were higher in the rainy season than in the dry season. Significant
      differences in the soil moisture content, and IN, NH(4) (+)-N and NO(3) (-)-N
      concentration was detected for both land uses and sampling season effects, as
      well as interactions. Higher concentrations of NH(4) (+)-N were measured at the
      upper slopes of all sites, but NO(3) (-)-N concentrations were highest at the
      lower slope in the rubber plantations and lowest at the lower slopes at all
      other. Thus, the conversion of tropical forests to rubber and tea plantations can
      have a profound effect on soil NH(4) (+)-N and NO(3) (-)-N concentrations.
      Options for improved soil management in plantations are discussed.

PMID- 22986586
TI  - Plasmid-mediated bioaugmentation of sequencing batch reactors for enhancement of
      2,4-dichlorophenoxyacetic acid removal in wastewater using plasmid pJP4.
AB  - Plasmid-mediated bioaugmentation was demonstrated using sequencing batch reactors
      (SBRs) for enhancing 2,4-dichlorophenoxyacetic acid (2,4-D) removal by
      introducing Cupriavidus necator JMP134 and Escherichia coli HB101 harboring 2,4-D
      degrading plasmid pJP4. C. necator JMP134(pJP4) can mineralize and grow on 2,4-D,
      while E. coli HB101(pJP4) cannot assimilate 2,4-D because it lacks the
      chromosomal genes to degrade the intermediates. The SBR with C. necator
      JMP134(pJP4) showed 100 % removal against 200 mg/l of 2,4-D just after its
      introduction, after which 2,4-D removal dropped to 0 % on day 7 with the decline
      in viability of the introduced strain. The SBR with E. coli HB101(pJP4) showed
      low 2,4-D removal, i.e., below 10 %, until day 7. Transconjugant strains of
      Pseudomonas and Achromobacter isolated on day 7 could not grow on 2,4-D. Both
      SBRs started removing 2,4-D at 100 % after day 16 with the appearance of 2,4-D
      degrading transconjugants belonging to Achromobacter, Burkholderia, Cupriavidus,
      and Pandoraea. After the influent 2,4-D concentration was increased to 500 mg/l
      on day 65, the SBR with E. coli HB101(pJP4) maintained stable 2,4-D removal of
      more than 95 %. Although the SBR with C. necator JMP134(pJP4) showed a temporal
      depression of 2,4-D removal of 65 % on day 76, almost 100 % removal was achieved
      thereafter. During this period, transconjugants isolated from both SBRs were
      mainly Achromobacter with high 2,4-D-degrading capability. In conclusion, plasmid
      mediated bioaugmentation can enhance the degradation capability of activated
      sludge regardless of the survival of introduced strains and their 2,4-D
      degradation capacity.

PMID- 22986588
TI  - Effects of dietary supplementation of inosine monophosphate on growth
      performance, innate immunity and disease resistance of olive flounder
      (Paralichthys olivaceus).
AB  - This study was investigated to examine the effects of dietary inosine
      monophosphate (IMP) supplementation on growth performance, feed utilization,
      innate immunity, hematological parameters and disease resistance of juvenile
      olive flounder. Five experimental diets were formulated to contain IMP at levels
      of 0, 0.1, 0.2, 0.4 and 1.0%. All diets were maintained isonitrogenous (48% crude
      protein) and isocaloric (20.7 MJ/kg diet). Triplicate groups of olive flounder
      (initial body weight, 7.5 +/- 0.02 g) were fed one of the experimental diets to
      apparent satiation (twice a day) for 14 weeks. Final body weight of fish fed 0.1
      0.2% IMP were significantly higher than that of fish fed the 1.0% IMP. Groups of
      fish fed 0.2 or 0.4% IMP diet had significantly higher myeloperoxidase and
      lysozyme activities than fish fed the control diet. However, nitro-blue
      tetrazolium and superoxide dismutase activities were not significantly different
      among all treatments. In the challenge test against Streptococcus iniae,
      cumulative mortality of fish fed IMP supplemented diets was significantly lower
      (15%, 4%, 4% and 9% for 0.1%, 0.2%, 0.4% and 1.0% IMP, respectively) than that of
      fish fed the control group (87%). The results suggest that IMP supplementation of
      0.46-1.84 g into a kg of fish meal based diet (0.1-0.4% IMP product) can enhance
      innate immunity and disease resistance of olive flounder.

PMID- 22986587
TI  - TMEM70: a mutational hot spot in nuclear ATP synthase deficiency with a pivotal
      role in complex V biogenesis.
AB  - Mammalian complex V (F1F0-ATP synthase or ATPase) uses the proton gradient to
      generate ATP during oxidative phosphorylation and requires several helper
      proteins, including TMEM70, to form the holoenzyme in a stepwise process in which
      nuclear DNA is combined with mitochondrial DNA-encoded subunits. We report the
      clinical and molecular findings in three patients presenting lactic acidosis, 3
      methylglutaconic aciduria, and hypertrophic cardiomyopathy. All three showed an
      isolated defect of fully assembled ATP synthase in association with a "common"
      (c.317-2A > G) and a new (c.628A > C/p.T210P) variant in TMEM70. Interestingly,
      one of the patients also showed nitric oxide-responsive pulmonary arterial
      hypertension, a finding never before associated with TMEM70 deficiency. In
      addition to widening the clinical and mutational spectrum of defective ATP
      synthase, our study also suggests that mutant TMEM70 associates in high molecular
      weight complexes (470-550 kDa) when expressed in Hela cells and exerts a direct
      action in ATP synthase biogenesis and assembly, mediating the incorporation of F1
      moieties.

PMID- 22986589
TI  - Particularity and universality of a putative Gram-negative bacteria-binding
      protein (GNBP) gene from amphioxus (Branchiostoma belcheri): insights into the
      function and evolution of GNBP.
AB  - Gram-negative bacteria-binding proteins (GNBPs) are important pattern recognition
      proteins (PRPs), which can initiate host defense in response to pathogen surface
      molecules. The roles of GNBP in innate immunity of arthropods and molluscs have
      recently been reported. However, the GNBP gene has not been characterized in the
      species of higher evolutionary status yet. In this study, we identified and
      characterized an amphioxus GNBP gene (designated as AmphiGNBP). First, we
      identified and cloned the AmphiGNBP and found that the AmphiGNBP encodes a
      putative protein with 558 amino acids, which contains a conserved beta-1, 3
      glucan recognizing and binding domain. Second, we found that the AmphiGNBP
      encodes two extra WSC (cell Wall integrity and Stress response Component)
      domains, which are unique in AmphiGNBP protein. The two WSC domains of AmphiGNBP
      protein coupled with the expansion of amphioxus immunity repertoire might undergo
      intensive domain shuffling during the age of the Cambrian explosion. Finally, we
      found that the AmphiGNBP was mainly expressed in immune tissues, such as hepatic
      cecum and intestine, and the expression of AmphiGNBP was affected after LPS
      stimulation. In conclusion, our findings disclose the particularity and
      universality of AmphiGNBP and provide profound insights into the function and
      evolution of GNBP.

PMID- 22986590
TI  - Grouper translationally controlled tumor protein prevents cell death and inhibits
      the replication of Singapore grouper iridovirus (SGIV).
AB  - Translationally controlled tumor protein (TCTP) is an important molecule involved
      in multiple biological processes, such as cell growth, cell cycle progression,
      malignant transformation, and enhancement of the anti-apoptotic activity. In this
      study, the TCTP from orange-spotted grouper Epinephelus coioides (Ec-TCTP) was
      cloned and characterized. The full-length cDNA of Ec-TCTP was comprised of 1057
      bp with a 510 bp open reading frame that encodes a putative protein of 170 amino
      acids. Recombinant Ec-TCTP (rEc-TCTP) was expressed in Escherichia BL21 (DE3) and
      purified for mouse anti-Ec-TCTP serum preparation. The rEc-TCTP fusion protein
      was demonstrated to possess antioxidant activity, which conferred resistance to
      H(2)O(2) damage. Quantitative real-time PCR analysis revealed that Ec-TCTP mRNA
      is predominately expressed in the liver, and the expression was up-regulated in
      the liver of grouper after viral challenge with Singapore grouper iridovirus
      (SGIV). Intracellular localization revealed that Ec-TCTP expression was
      distributed predominantly in the cytoplasm. Although human TCTP has a role in
      apoptosis regulation, it is not known if grouper TCTP has any role in apoptosis
      regulation. Strikingly, grouper TCTP, when overexpressed in fathead minnow (FHM)
      cells, protected them from cell death induced by cycloheximide (CHX). In
      addition, overexpressed Ec-TCTP in grouper spleen (GS) cells inhibited the
      replication of SGIV. These results suggest that Ec-TCTP may play a critical role
      in their response to SGIV infection, through regulation of a cell death pathway
      that is common to fish and humans.

PMID- 22986591
TI  - Clinical application of motor pathway mapping using diffusion tensor imaging
      tractography and intraoperative direct subcortical stimulation in cerebral glioma
      surgery:  a prospective cohort study.
AB  - BACKGROUND: Glioma surgery in eloquent areas remains a challenge because of the
      risk of postoperative motor deficits. OBJECTIVE: To prospectively evaluate the
      efficiency of using a combination of diffusion tensor imaging (DTI) tractography
      functional neuronavigation and direct subcortical stimulation (DsCS) to yield a
      maximally safe resection of cerebral glioma in eloquent areas. METHODS: A
      prospective cohort study was conducted in 58 subjects with an initial diagnosis
      of primary cerebral glioma within or adjacent to the pyramidal tract (PT). The
      white matter beneath the resection cavity was stimulated along the PT, which was
      visualized with DTI tractography. The intercept between the PT border and DsCS
      site was measured. The sensitivity and specificity of DTI tractography for PT
      mapping were evaluated. The efficiency of the combined use of both techniques on
      motor function preservation was assessed. RESULTS: Postoperative analysis showed
      gross total resection in 40 patients (69.0%). Seventeen patients (29.3%)
      experienced postoperative worsening; 1-month motor deficit was observed in 6
      subjects (10.3%). DsCS verified a high concordance rate with DTI tractography for
      PT mapping. The sensitivity and specificity of DTI were 92.6% and 93.2%,
      respectively. The intercepts between positive DsCS sites and imaged PTs were 2.0
      to 14.7 mm (5.2 +/- 2.2 mm). The 6-month Karnofsky performance scale scores in 50
      postoperative subjects were significantly increased compared with their
      preoperative scores. CONCLUSION: DTI tractography is effective but not completely
      reliable in delineating the descending motor pathways. Integration of DTI and
      DsCS favors patient-specific surgery for cerebral glioma in eloquent areas.

PMID- 22986592
TI  - Levels of evidence in the neurosurgical literature:  more tribulations than
      trials.
AB  - BACKGROUND: The importance of evidence-based medicine has been well documented
      and supported across various surgical subspecialties. OBJECTIVE: To quantify the
      levels of evidence across publications in the neurosurgical literature, to assess
      the change in evidence over time, and to indicate predictive factors of higher
      level evidence. METHODS: We reviewed the levels of evidence across published
      clinical studies in 3 neurosurgical journals from 2009 to 2010. Randomized trials
      were evaluated by use of the Detsky quality of reporting scale. Levels-of
      evidence data for the same journals in 1999 were obtained from the literature,
      and regression analysis was performed to identify predictive factors for higher
      level evidence. RESULTS: Of 660 eligible articles, 14 (2.1%) were Level I, 54
      (8.2%) were level II, 73 (11.1%) were Level III, 287 (43.5%) were level IV, and
      232 (35.2%) were level V. The number of level I studies decreased significantly
      between 1999 and 2010 (3.4% vs. 2.1%, respectively; P = .01). Seven randomized
      clinical trials were identified, and 1 trial had significant methodological
      limitations (mean Detsky index = 16.3; SD = 1.8). Publications with larger sample
      size were significantly associated with higher levels of evidence (levels I and
      II; odds ratio, 1.7; 95% confidence interval, 1.45-2.05; P = .001). The ratio of
      higher levels of evidence to lower levels was 0.11. CONCLUSION: Higher levels of
      evidence (levels I and II) represent only 1 in 10 neurosurgical clinical papers
      in the top neurosurgical journals. Increased awareness of the need for better
      evidence in the field through education and adoption of the levels of evidence
      may improve the conduct and publication of prospective studies.

PMID- 22986593
TI  - Revisiting angioplasty without stenting for symptomatic intracranial
      atherosclerotic stenosis after the stenting and aggressive medical management for
      preventing recurrent stroke in intracranial stenosis (SAMMPRIS) study.
AB  - BACKGROUND: The Stenting and Aggressive Medical Management for Preventing
      Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study stopped recruiting
      patients because of higher-than-expected perioperative morbidity of primary
      stenting in patients with symptomatic intracranial stenosis. An alternative
      treatment, submaximal angioplasty without stenting, performed concurrently with
      SAMMPRIS, may offer revascularization benefits with a lower incidence of stenting
      related risks. OBJECTIVE: To present the results of a consecutive case series of
      primary submaximal angioplasty procedures performed for symptomatic severe
      atherosclerotic intracranial stenosis refractory to medical treatment. METHODS: A
      database review identified primary submaximal angioplasty procedures performed in
      41 patients for the treatment of >70% intracranial stenosis associated with an
      acute, symptomatic ischemic event in the distribution of the diseased vessel. For
      results analysis, 30-day events were reported as a percentage of patients
      treated. One-year periprocedural and ischemic event--free survival was reported
      as a percentage of all patients treated and displayed graphically with a Kaplan
      Meier survival curve. RESULTS: Three events in 41 patients included 1
      intraprocedural vessel perforation, 1 reperfusion hemorrhage < 24 hours
      postoperatively, and 1 transient ischemic attack 3 months postprocedurally (30
      day event rate, 2 of 41, 4.9%). Median clinical follow-up duration after
      submaximal angioplasty was 19 months, with >= 1 year of follow-up available for
      32 patients. One-year perioperative and ischemic event-free survival was high (29
      of 32 patients, 91%). CONCLUSION: In this series, periprocedural safety of
      submaximal angioplasty in the setting of acute, symptomatic atherosclerotic
      intracranial stenosis was demonstrated. Although direct comparison is impossible
      because many patients were ineligible for stenting procedures, the complication
      profile compares favorably with rates of identically defined event-free survival
      for patients randomized to the medical (88%) and surgical (77%) arms of SAMMPRIS
      despite the absence of aggressive medical management.

PMID- 22986594
TI  - The anatomically intact but electrically unresponsive facial nerve in vestibular
      schwannoma surgery.
AB  - BACKGROUND: Permanent facial nerve (FN) paresis after vestibular schwannoma
      surgery is distressing to both the patient and surgeon. Intraoperative
      electrophysiological testing has proven invaluable in reducing the incidence of
      FN injury and may assist in prognosticating long-term function. OBJECTIVE: To
      report definitive FN outcomes among a cohort of patients with an unevokable but
      anatomically intact seventh nerve after microsurgical vestibular schwannoma
      resection. METHODS: All patients undergoing vestibular schwannoma surgery between
      2000 and 2010 at a single tertiary academic referral center were identified.
      Intraoperative FN monitoring data and definitive FN outcomes were reviewed, and
      all patients with an anatomically intact but electrically unresponsive FN were
      included. RESULTS: Eleven patients met the inclusion criteria. The median
      preoperative and definitive postoperative FN scores were House-Brackmann grades 1
      and 3, respectively. The median time to definitive FN recovery was 9.4 months.
      CONCLUSION: These data demonstrate that even among this extreme subset, modern
      electroprognostic testing strategies are incapable of reliably predicting poor
      outcomes. Therefore, if FN continuity is maintained, attempts at same-surgery FN
      repair should not be pursued.

PMID- 22986596
TI  - Determination of the minimum improvement in pain, disability, and health state
      associated with cost-effectiveness:  introduction of the concept of minimum cost
      effective difference.
AB  - BACKGROUND: Minimum clinical important difference (MCID) has been adopted as the
      smallest improvement in patient-reported outcome needed to achieve a level of
      improvement thought to be meaningful to patients. OBJECTIVE: To use a common MCID
      calculation method with a cost-utility threshold anchor to introduce the concept
      of minimum cost-effective difference (MCED). METHODS: Forty-five patients
      undergoing transforaminal lumbar interbody fusion for degenerative
      spondylolisthesis were included. Outcome questionnaires were administered before
      and 2 years after surgery. Total cost per quality-adjusted life-year (QALY)
      gained was calculated for each patient. MCED was determined from receiver
      operating characteristic curve analysis with a cost-effective anchor of <
      $50,000/QALY and < $75,000/QALY. MCID was determined with the health transition
      item as the anchor. RESULTS: Significant improvement was observed 2 years after
      transforaminal lumbar interbody fusion for all outcome measures. Mean total cost
      per QALY gained at 2 years was $42,854. MCED was greater than MCID for each
      outcome measure, meaning that a greater improvement was required to represent
      cost-effectiveness than a clinically meaningful improvement to patients. The area
      under the receiver-operating characteristic curve was consistently >= 0.70 with
      both cost-effective anchors, suggesting that outcome change scores were accurate
      predictors of cost-effectiveness. Mean cost per QALY gained was significantly
      lower for patients achieving compared with those not achieving an MCED in visual
      analog scale for leg pain ($43,560 vs. $112,087), visual analog scale for back
      pain ($41,280 vs. $129,440), Oswestry disability index ($30,954 vs. $121,750),
      and EuroQol 5D ($35,800 vs. $189,412). CONCLUSION: MCED serves as the smallest
      improvement in an outcome instrument that is associated with a cost-effective
      response to surgery. With the use of cost-effective anchor of <  $50,000/QALY,
      MCED after transforaminal lumbar interbody fusion was 4 points for visual analog
      scale for low back pain, 3 points for visual analog scale for leg pain, 22 points
      for Oswestry disability index, and 0.31 QALYs for EuroQol 5D.

PMID- 22986595
TI  - Cerebellar arteriovenous malformations:  anatomic subtypes, surgical results, and
      increased predictive accuracy of the supplementary grading system.
AB  - BACKGROUND: Anatomic diversity among cerebellar arteriovenous malformations
      (AVMs) calls for a classification that is intuitive and surgically informative.
      Selection tools like the Spetzler-Martin grading system are designed to work best
      with cerebral AVMs but have shortcomings with cerebellar AVMs. OBJECTIVE: To
      define subtypes of cerebellar AVMs that clarify anatomy and surgical management,
      to determine results according to subtypes, and to compare predictive accuracies
      of the Spetzler-Martin and supplementary systems. METHODS: From a consecutive
      surgical series of 500 patients, 60 had cerebellar AVMs, 39 had brainstem AVMs
      and were excluded, and 401 had cerebral AVMs. RESULTS: Cerebellar AVM subtypes
      were as follows: 18 vermian, 13 suboccipital, 12 tentorial, 12 petrosal, and 5
      tonsillar. Patients with tonsillar and tentorial AVMs fared best. Cerebellar AVMs
      presented with hemorrhage more than cerebral AVMs (P < .001). Cerebellar AVMs
      were more likely to drain deep (P = .04) and less likely to be eloquent (P <
      .001). The predictive accuracy of the supplementary grade was better than that of
      the Spetzler-Martin grade with cerebellar AVMs (areas under the receiver
      operating characteristic curve, 0.74 and 0.59, respectively). The predictive
      accuracy of the supplementary system was consistent for cerebral and cerebellar
      AVMs, whereas that of the Spetzler-Martin system was greater with cerebral AVMs.
      CONCLUSION: Patients with cerebellar AVMs present with hemorrhage more often than
      patients with cerebral AVMs, justifying an aggressive treatment posture. The
      supplementary system is better than the Spetzler-Martin system at predicting
      outcomes after cerebellar AVM resection. Key components of the Spetzler-Martin
      system such as venous drainage and eloquence are distorted by cerebellar anatomy
      in ways that components of the supplementary system are not.

PMID- 22986597
TI  - Safety and efficacy of intraoperative angiography in craniotomies for cerebral
      aneurysms and arteriovenous malformations: a review of 1093 consecutive cases.
AB  - BACKGROUND: In an era of indocyanine angiography, the routine use of
      intraoperative angiography (IOA) in the surgical treatment of aneurysms and
      vascular malformations is controversial. OBJECTIVE: To retrospectively assess the
      safety and efficacy of IOA and to determine predictors of surgical revision.
      METHODS: Between 2003 and 2011, IOA was performed during surgical treatment of
      976 aneurysms, 101 arteriovenous malformations (AVMs), and 16 arteriovenous
      fistulas. RESULTS: In 80 of 976 aneurysms (8.2%), IOA prompted clip
      repositioning. The reason for readjustment was residual aneurysm in 54.7%, parent
      vessel occlusion in 42.9%, and both in 2.4% of cases. In multivariate analysis,
      increasing aneurysm size (P, .001), ruptured aneurysm (P, .001), and increasing
      number of vessels injected (P, .001) were strong predictors of clip readjustment.
      There was a strong trend for posterior circulation aneurysm location to predict
      clip repositioning (P = .06). IOA revealed residual nidus/ fistula requiring
      further intervention in 9 of 101 AVMs (8.9%) and 3 of 16 arteriovenous fistulas
      (18.8%). Of 9 AVMs requiring a surgical revision, 2 (22.2%) were Spetzler-Martin
      grade II, 5 (55.6%) were grade III, and 2 (22.2%) were grade IV. Mean Spetzler
      Martin grade was 3.0 in AVMs requiring surgical revision compared with 2.3 in
      those not requiring revision (P = .05). IOA-related complications were all
      transient or minor and occurred in 0.99% of patients; none resulted in permanent
      morbidity. CONCLUSION: IOA remains a valuable tool in the surgical treatment of
      brain vascular abnormalities, guiding surgical re-exploration in .8% of cases.
      Easy access to an angiographer and routine use of IOA are important factors
      contributing to procedural safety and efficacy.

PMID- 22986598
TI  - Transvenous coil embolization of an intraorbital arteriovenous fistula:  case
      report and review of the literature.
AB  - BACKGROUND AND IMPORTANCE: Purely intraorbital arteriovenous fistulas (AVFs),
      which are rare vascular malformations that clinically mimic carotid-cavernous
      fistulas (CCFs), involve a fistula from the ophthalmic artery to 1 of the
      draining ophthalmic veins. We describe a case of an intraorbital AVF treated with
      transvenous endovascular coil embolization via the inferior petrosal sinus (IPS)
      route and review the literature on this rare entity. CLINICAL PRESENTATION: An 81
      year-old woman sought treatment after 7 days of progressive left-sided visual
      acuity loss, chemosis, and lateral rectus palsy. Magnetic resonance imaging
      demonstrated dilated vascularity in the left orbit raising suspicions for a CCF.
      Cerebral angiography showed a purely intraorbital AVF with a fistula between the
      left ophthalmic artery and superior ophthalmic vein (SOV). Transvenous selective
      catheterization of the fistula was performed by successfully navigating the
      ipsilateral IPS to the cavernous sinus and SOV. The fistula was then embolized
      using detachable coils. The patient was discharged the next day. Three weeks
      after embolization, her ocular symptoms and findings had resolved. CONCLUSION:
      Intraorbital AVFs are a rare type of AVF that can be treated by direct surgical
      ligation, transarterial embolization, or transvenous embolization. We
      successfully navigated the IPS, which is frequently stenotic or occluded
      secondary to chronically increased fistulous drainage, and utilized this route to
      embolize the fistula with detachable coils.

PMID- 22986599
TI  - Middle fossa approach for total resection of petrous apex cholesterol granulomas:
      use of vascularized galeofascial flap preventing recurrence.
AB  - BACKGROUND: Cholesterol granulomas (CGs) of the petrous apex (PA) are rare,
      benign, expanding lesions. Surgical treatment is recommended for patients with
      symptomatic disease; however, the optimal surgical procedure is still
      controversial due to high recurrence rates. The main treatment strategy is
      divided into drainage and complete resection. OBJECTIVE: We advocate radical
      resection of the lesion by the middle fossa approach and reconstruction with a
      vascularized galeofascial flap. METHODS: A 10-year retrospective case review of
      17 patients undergoing surgical treatment of PA CGs between 2000 and 2010 was
      undertaken. Operative outcomes and surgical complications were analyzed. In
      addition, our operative method and the related anatomy are described from
      cadaveric dissections. RESULTS: All but 1 patient was operated on via a middle
      fossa approach. Using the middle fossa approach, radical resection of all PA CGs
      was achieved with obliteration of the cyst cavity using a vascularized flap.
      Important surrounding structures included the internal auditory canal, cochlea,
      petrous carotid artery, and abducens nerve. There was 1 death caused by internal
      carotid artery occlusion. No other major complications or cranial nerve deficits
      occurred postoperatively. Clinical recurrence occurred in 1 patient (5.9%).
      CONCLUSION: Our technique of radical resection and reconstruction with a
      vascularized flap has the advantage of being less invasive with less cosmetic
      deformity and allows preservation of cranial nerve function with a low recurrence
      rate. Knowledge of the surgical anatomy and the characteristics of CG is prudent
      because important neurovascular structures may be exposed behind the CG wall due
      to bony erosion.

PMID- 22986601
TI  - Evidence for intracranial pressure monitoring:  a very demanding challenge.

PMID- 22986600
TI  - Traumatic brain injury in Latin America: lifespan analysis randomized control
      trial protocol*.
AB  - BACKGROUND: Although in the developed world the intracranial pressure (ICP)
      monitor is considered the standard of care for patients with severe traumatic
      brain injury (TBI), its usefulness to direct treatment decisions has never been
      tested rigorously. OBJECTIVE: The primary focus was to conduct a high-quality,
      randomized, controlled trial to determine whether ICP monitoring used to direct
      TBI treatment improves patient outcomes. By providing education, equipment, and
      structure, the project will enhance the research capacity of the collaborating
      investigators and will foster the collaborations established during earlier
      studies. METHODS: Study centers were selected that routinely treated ICP based on
      clinical examination and computed tomography imaging using internal protocols. We
      randomized patients to either an ICP monitor group or an imaging and clinical
      examination group. Treatment decisions for the ICP monitor group are guided by
      ICP monitoring based on established guidelines. Treatment decisions for the
      imaging and clinical examination group are made using a single protocol derived
      from those previously being used at those centers. EXPECTED OUTCOMES: There are 2
      study hypotheses: (1) patients with severe TBI whose acute care treatment is
      managed using ICP monitors will have improved outcomes and 2) incorporating ICP
      monitoring in the care of patients with severe TBI will minimize complications
      and decrease length of intensive care unit stay. DISCUSSION: This clinical trial
      tests the effectiveness of a management protocol based on technology considered
      pivotal to brain trauma treatment in the developed world: the ICP monitor. A
      randomized, controlled trial of ICP monitoring has never been performed-a
      critical gap in the evidence base that supports the role of ICP monitoring in TBI
      care. As such, the results of this randomized, controlled trial will have global
      implications regardless of the level of development of the trauma system.

PMID- 22986602
TI  - Management of a recurrent coiled giant posterior cerebral artery aneurysm with
      trapping and thrombectomy:  3-dimensional operative video.

PMID- 22986603
TI  - Long-term results of gamma knife surgery for partially embolized arteriovenous
      malformations.
AB  - BACKGROUND: The effectiveness and risk of gamma knife surgery (GKS) in the
      management of partially embolized cerebral arteriovenous malformations (AVMs)
      remain to be elucidated. OBJECTIVE: To evaluate the long-term imaging and
      clinical outcomes of GKS in AVM patients who had undergone previous partial
      embolization and compare the results with patients treated with GKS alone.
      METHODS: A total of 215 embolized AVMs were analyzed. The mean patient age was
      32.9 years. The mean volume of the nidus was 4.6 mL (range, 0.1-29.4 mL), and the
      mean prescription dose was 19.6 Gy (range, 4-28 Gy). This group was compared with
      729 nonembolized AVMs. RESULTS: After embolization and GKS, angiographically
      confirmed total obliteration of the AVMs was significantly lower (33%) compared
      with patients in whom GKS was used alone (60.9%; P < .001). However, the mean
      nidus size was larger and the Spetzler-Martin grade was higher for the embolized
      AVMs compared with the nonembolized AVMs. Radiation-induced changes occurred more
      often in the embolized (43.4%) than the nonembolized (33.4%) AVMs (P = .028).
      Permanent neurological deficits associated with radiation-induced changes
      occurred in 2.7% of the embolized compared with 1.3% of the nonembolized patients
      (P = .14). CONCLUSION: In our retrospective and historical series, the long-term
      results suggest that the obliteration rate is significantly lower in embolized
      AVMs compared with nonembolized AVMs, also because of the fact that the combined
      treatment is applied to higher grade AVMs; the percentage of grade III-V AVMs was
      58.6% and 48.8% for nonembolized AVMs.

PMID- 22986604
TI  - A quantitative assessment of the accuracy and reliability of O-arm images for
      deep brain stimulation surgery.
AB  - BACKGROUND: Deep brain stimulation (DBS) surgery has an average accuracy of 2 to
      3 mm (range, 0-6 mm). Intraoperative detection of track location may be useful in
      interpreting physiological results and thus limit the number of brain
      penetrations as well as decrease the incidence of reoperations. The O-arm has
      been used to identify the DBS lead position; however, early results have
      indicated a significant discrepancy with lead position on postoperative imaging.
      OBJECTIVE: This prospective study was conducted to determine the accuracy and
      reliability of fiducial and track localization and to assess the accuracy of O
      arm image-based registration. The computed tomography (CT) image was considered
      the gold standard, and so for this study, the locations of all objects on the O
      arm image were compared with their CT location. METHODS: Thirty-three DBS
      surgeries were performed using the O-arm to image each track with detailed
      analysis of fiducial and track localization accuracy. Twenty-one subsequent
      surgeries were performed using O-arm registration. Only the final lead position
      was assessed in these individuals. RESULTS: The measurement error of the system
      was 0.7 mm, with a maximum error of 1.9 mm. Twenty-two percent of the parallel
      tracks through the BenGun exceeded this error and demonstrated the ability of the
      O-arm to detect these skewed tracks. The accuracy of final lead position was 2.04
      mm in procedures with registration based on an O-arm image. This was not
      significantly different from CT-based registration at 2.16 mm. CONCLUSION: The O
      arm was able to detect skewed tracks and provide registration accuracy equivalent
      to a CT scan.

PMID- 22986605
TI  - Superficial temporal artery dissection:  a technical note.
AB  - BACKGROUND: Dissection of the superficial temporal artery (STA) is often required
      in preparation for a bypass procedure. Traditionally, dissection of the STA
      involves a direct cutdown on the artery after marking the course of the artery on
      the skin with the help of a Doppler ultrasound probe. OBJECTIVE: We describe a
      method that takes advantage of the position of the STA superficial to the
      temporal fascia. METHODS: The technique was used in a total of 38 procedures in
      32 patients to create synangiosis or extracranial-intracranial STA bypasses. The
      STA was dissected using a blunt malleable brain retractor that was inserted into
      the subgaleal plane directly over the STA, allowing creation of a linear incision
      and concurrent protection of the STA in its bed. Either computed tomography- or
      catheter-based angiography was used to evaluate the patency postoperatively.
      RESULTS: All STA vessels were dissected without complications or injury to the
      graft vessel. The sole complication was a superficial wound breakdown in a
      synangiosis case. Postoperative angiography demonstrated patency in all but 1 of
      the 24 bypass cases (95.8%). CONCLUSION: We describe a method that takes
      advantage of the position of the STA superficial to the temporal fascia to allow
      rapid, safe, and efficacious dissection. The incision is linear and easier to
      manage and close. In our series, there were no technical complications related to
      the dissection of the STA.

PMID- 22986606
TI  - Genomic sequence and analysis of EhV-99B1, a new coccolithovirus from the
      Norwegian fjords.
AB  - Coccolithoviruses are giant dsDNA viruses that infect Emiliania huxleyi, the most
      ubiquitous marine microalga. Here, we present the genome of the latest
      coccolithovirus strain to be sequenced, EhV-99B1, and compare it with two other
      coccolithovirus genomes (EhV-86 and EhV-163). EhV-99B1 shares a pairwise
      nucleotide identity of 98% with EhV-163 (the two strains were isolated from the
      same Norwegian fjord but in different years), and just 96.5% with EhV-86
      (isolated in the same spring as EhV-99B1 but in the English Channel). We
      confirmed and extended the list of relevant genomic differences between these
      EhVs from the Norwegian fjord and EhVs from the English Channel, namely the
      removal/insertions of: a phosphate permease, an endonuclease, a transposase, and
      two specific tRNAs. As a whole, this study provided new clues and insights into
      the diversity and mechanisms driving the evolution of these large oceanic
      viruses, in particular those processes involving selfish genetic elements.

PMID- 22986608
TI  - Angiotensin-converting enzyme inhibitor-induced unilateral tongue angioedema.
AB  - Angioedema is a frequently reported side effect of angiotensin-converting enzyme
      inhibitors. The literature suggests that immunosuppressed transplant patients are
      at an increased risk for this adverse condition. A 62-year-old African American
      man presented with acute unilateral angioedema attributed to angiotensin
      converting enzyme inhibitor initiation. A PubMed literature search regarding
      unilateral angioedema produced only 3 reported cases confirming an uncommon
      presentation of an otherwise common adverse drug event. The cases raised
      questions regarding evidence-based management of drug-induced angioedema,
      effectiveness of current medical management regimens and the potential of other
      treatment options. Our objective was to review the presentation, diagnosis and
      acute management of a common adverse drug effect based on an uncommon patient
      presentation.

PMID- 22986607
TI  - Effect of CYP2D6*10 and APOE polymorphisms on the efficacy of donepezil in
      patients with Alzheimer's disease.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of CYP2D6*10 and
      APOE polymorphisms on both steady-state plasma concentrations (Cp) and clinical
      response of donepezil in patients with mild-to-moderate Alzheimer's disease (AD).
      METHODS: A total of 110 Chinese AD patients participated in this study. Patients
      were treated with 5 to 10 mg of donepezil daily for 6 months. The genotypes of
      CYP2D6*10 and APOE were analyzed by polymerase chain reaction-restriction
      fragment length polymorphism. The steady-state Cp of donepezil was measured by
      high-performance liquid chromatography-tandem mass spectrometric assay method.
      The cognition of patients was evaluated at baseline and at 6-month follow-up by
      Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive
      subscale. RESULTS: At 6-month follow-up, 56 of 96 patients (58.3%) were evaluated
      as responders and 40 patients (41.7%) as nonresponders to donepezil treatment. A
      significantly higher frequency of patients with genotypes CYP2D6*1/*10 and
      *10/*10 were found in responders than in nonresponders (P < 0.05). Besides,
      patients with CYP2D6*1/*10 and *10/*10 genotypes had higher Cp of donepezil and
      improved cognition scores than those with CYP2D6*1/*1 genotype (P < 0.05).
      However, the frequency of APOE [Latin Small Letter Open E]4 carriers and
      noncarriers showed no difference between the 2 groups (P > 0.05). CONCLUSIONS: AD
      patients with mutant allele (*10) in CYP2D6 gene may respond better to donepezil
      than those with wild allele (*1). We did not find the relationship between APOE
      [Latin Small Letter Open E]4 status and the efficacy of donepezil in our study.

PMID- 22986609
TI  - Malignant solitary fibrous tumor of the right atrium.
AB  - Cardiac solitary fibrous tumors (SFTs) are extremely rare, with only 4 cases
      described to date. Here, we describe the case of a 55-year-old man with a
      primary, malignant SFT that arose in the right atrium of his heart. His
      presenting complaint was of chest distress and shortness of breath. Physical
      examination revealed jugular venous engorgement. Computed tomography showed a
      tumor of 15 * 10 * 8 cm in the anterior mediastinum. The tumor was surgically
      resected under cardiopulmonary bypass. A grayish white neoplasm was discovered
      lying within the right atrium. The histological appearance of the tumor was of a
      hypercellular distribution of spindle cells with nuclear atypia, arranged in a
      storiform pattern and intermixed with collagenous stroma. Immunohistochemistry
      showed that the tumor was positive for CD34. Based on the aforementioned
      features, the diagnosis of malignant SFT was made. The patient subsequently died
      as a result of respiratory and circulatory failure.

PMID- 22986610
TI  - Severe anion gap metabolic acidosis from acetaminophen use secondary to 5
      oxoproline (pyroglutamic acid) accumulation.
AB  - Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice.
      Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases
      of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation
      resulting from acetaminophen consumption: the first case caused by acute one-time
      ingestion of large quantities of acetaminophen and the second case caused by
      chronic repeated ingestion in a patient with chronic liver disease. Recognition
      of this entity facilitated timely diagnosis and effective treatment. Given
      acetaminophen is commonly used over the counter medication, increased recognition
      of this adverse effect is of important clinical significance.

PMID- 22986611
TI  - A retrospective analysis of cytogenetic and clinical characteristics in patients
      with multiple myeloma.
AB  - BACKGROUND: Cytogenetic alterations in patients with multiple myeloma (MM)
      represent important risk factors in terms of prognosis. In this study, the impact
      of the cytogenetic aberrations of MM on patient clinical features and outcome was
      investigated. METHODS: Conventional cytogenetic analysis with R-banding technique
      and molecular cytogenetic characterization by interphase fluorescence in situ
      hybridization (FISH) were used to detect aberrant chromosomal arrangements,
      including 17p13 and 13q14 deletions, 14q32 rearrangement and 1q21 amplification,
      in bone marrow nucleated cells from 65 patients. RESULTS: About 16.9% of patients
      showed aberrations by conventional cytogenetic analysis, whereas 49.2% of
      patients showed aberrations by interphase FISH analysis. Abnormalities of 13q14,
      1q21, 14q32 and 17p13 were detected in 27.7%, 13.8%, 16.9% and 29.2%,
      respectively. Patients with a 13q14 deletion or combined with 17p13 deletion
      frequently had a late stage of the disease, and tended to have elevated serum
      levels of beta2 microglobulin and lower levels of albumin. The progression-free
      survival and overall survival of FISH-positive patients were lower than for those
      without detectable abnormalities, especially in the conventional chemotherapy
      arm. CONCLUSIONS: These findings demonstrate that myeloma cells are prone to
      exhibiting a complex aberration and that FISH is superior to conventional
      cytogenetic analysis with a higher detection rate of chromosomal abnormalities.
      Patients with a 17p13 or 13q14 deletion, 14q32 rearrangement and 1q21
      amplification were more likely to have a poor prognosis for MM.

PMID- 22986612
TI  - Perfect timing, perfect storm: a chance observation of explosive overt visceral
      metastases.

PMID- 22986613
TI  - The role of TNF-alpha 308G>A polymorphism in the risk for ischemic stroke.
AB  - BACKGROUND: Stroke is a common health problem; however, its pathogenesis is not
      clear. Several studies have examined the association of -308G>A promoter
      polymorphism in the tumor necrosis factor-alpha gene (TNF-alpha) with ischemic
      stroke susceptibility. However, the results of these studies are inconsistent and
      the sample sizes of most of the studies were small. Thus, a meta-analysis was
      conducted to provide a more robust estimate of the effect of the TNF-alpha 308G>A
      polymorphism on the risk for ischemic stroke. METHODS: Odds ratios with 95%
      confidence intervals were used to assess the strength of the association of TNF
      alpha polymorphisms with ischemic stroke. Cochran's Q statistic and the
      inconsistency index (I) were used to explore heterogeneity. Egger's test and
      inverted funnel plots were used to investigate publication bias. RESULTS:
      Thirteen studies met the inclusion criteria involving 3515 cases and 3949
      controls. A significant association was found between TNF-alpha 308G>A
      polymorphism and the development of ischemic stroke in the Asian population.
      However, no statistically significant association was observed in the overall
      analysis and in the Caucasian population. In the subgroup analysis by age, a
      significant association was found in the juvenile and adult populations, showing
      that TNF-alpha 308G>A polymorphism is associated with the risk for juvenile
      ischemic stroke. CONCLUSIONS: This study suggests that TNF-alpha 308G>A
      polymorphism is associated with the risk for juvenile ischemic stroke, whereas it
      is a protective factor for ischemic stroke in Asians and the adult population.
      However, in the overall analysis and in Caucasians, a significant association was
      not found.

PMID- 22986614
TI  - Not every recurrent pelvic mass in a female is a leiomyoma.
AB  - Desmoid tumors are rare neoplasms. They occur mostly in females in their
      reproductive age and may present with pelvic pain and intestinal obstruction.
      These connective tissue neoplasms are because of uncontrolled proliferation of
      differentiated myofibroblasts. The cells may synthesize vast amounts of collagen
      fibers in response to various stimuli. We describe a case of a pelvic desmoid
      tumor simulating a uterine leiomyoma recurrence. We review the literature on the
      epidemiology and the treatment options for desmoid tumors and suggest a strong
      index of suspicion when a new pelvic mass arises in an adult with previous pelvic
      surgery. We advise a planned multidisciplinary treatment approach at the first
      hint of the diagnosis of desmoid tumor.

PMID- 22986615
TI  - Accuracy of anthropometric parameters in identification of high-risk patients
      predicted with cardiovascular risk models.
AB  - BACKGROUND: Overweight and obesity are associated with unfavorable outcomes on
      the cardiovascular system. Early detection of the patients' high risk for
      developing cardiovascular disease (CVD) is a primary care priority. Simple-to-use
      screening tools derived from anthropometric parameters and obesity-related
      indices could serve this purpose. METHODS: A total of 2,716 women and 1,132 men
      aged 18 years and older, free of known CVD at baseline were enrolled in this
      study. Ten-year risk of incident CVD based on 3 computational models, namely
      Systematic COronary Risk Evaluation (SCORE), United Kingdom Prospective Diabetes
      Study and Framingham was calculated and served as the main outcome event. Weight,
      height, body mass index, waist circumference, hip circumference, blood pressure,
      high-density lipoprotein cholesterol, total cholesterol, serum triglyceride,
      glycated hemoglobin A1c and fasting plasma glucose concentrations were also
      determined. RESULTS: Waist-to-hip ratio (WHR) had the largest area under the
      curve (AUC) in identification of all outcome variables (high-risk United Kingdom
      Prospective Diabetes Study, SCORE, Framingham; AUC: 0.64-0.69) in women and in 2
      of 3 (SCORE, Framingham; AUC: 0.62-0.64) in men; making it the best parameter
      followed by waist-to-height ratio and waist circumference. Body mass index and
      hip circumference consistently produced smaller AUC. WHR optimal cutoff points in
      prediction of outcome variables were in the range of 0.87 to 0.90 in women and
      0.90 to 0.94 in men. CONCLUSIONS: WHR is superior to other anthropometric
      parameters in identification of high-risk patients based on different CVD risk
      prediction models and can be used for screening purposes.

PMID- 22986616
TI  - Small cell carcinoma of the urinary bladder:  a rare tumor with propensity for
      hepatic involvement.
AB  - Small cell (neuroendocrine) carcinoma of the bladder is a rare entity, accounting
      for less than 1% of all bladder tumors. The authors report 2 new cases of the
      disease, both presenting with liver metastasis. In the first case, small cell
      carcinoma occurred in an 85-year-old woman as tumor recurrence of previous
      micropapillary carcinoma and urothelial carcinoma in situ, illustrating the
      common coexistence with conventional urothelial carcinoma. In the second case of
      a 58-year-old man, non-small cell tumor components were not observed. Accurate
      diagnosis of small cell carcinoma may be challenging. A panel of different
      antibodies, including neuron-specific enolase, chromogranin A, synaptophysin and
      CD56 (neural cell adhesion molecule) is recommended. In conclusion, small cell
      carcinoma represents a rare and aggressive form of bladder malignancy. As
      illustrated by the 2 cases and according to the literature review, the tumor
      shows a so far underrecognized propensity for hepatic involvement.

PMID- 22986617
TI  - Gene expression signature predicting high-grade prostate cancer responses to
      oxaliplatin.
AB  - Prostate cancer is one of the leading causes of cancer-related deaths among men.
      Several prognostic factors allow differentiation of low-grade tumors from high
      grade tumors with high metastatic potential. High-grade tumors are currently
      treated with hormone therapy, to which taxanes are added when the tumors become
      resistant to castration. Clinical trials with other anticancer agents did not
      take into account the genetic backgrounds of the tumors, and most trials
      demonstrated low response rates. Here we used an in silico approach to screen for
      drug candidates that might be used as alternatives to taxanes, on the basis of a
      published expression signature involving 86 genes that could distinguish high
      grade and low-grade tumors (Proc Natl Acad Sci USA 103:10991-10996, 2006). We
      explored the National Cancer Institute databases, which include data on the gene
      expression profiles of 60 human tumor cell lines and the in vitro sensitivities
      of the cell lines to anticancer drugs, and we identified several genes in the
      signature for which expression levels were correlated with chemosensitivity. As
      an example of the validation of this in silico approach, we identified a set of
      six genes for which expression levels could predict cell sensitivity to
      oxaliplatin but not cisplatin. This signature was validated in vitro through
      silencing of the genes in DU145, LNCaP, and C4-2B prostate cancer cells, which
      was accompanied by changes in oxaliplatin but not cisplatin cytotoxicity. These
      results demonstrate the relevance of our approach for the identification of both
      alternative treatments for high-grade prostate cancers and new biomarkers to
      predict clinical tumor responses.

PMID- 22986618
TI  - Chemical bonding in supermolecular flowers.
AB  - We report here a systematic study on the ability of molecular cages to bind
      (transition) metals. Starting from the superferrocenophane we investigate the
      incorporation of first-row transition metal (Sc-Zn) and alkaline-earth metal (Mg,
      Ca) double cations into these supermetallocenophane (super[5]phane) cages, and
      compare them with the corresponding metallocenes (Inorg. Chim. Acta, 2007, 360,
      179). Moreover, we also investigate the binding of neutral and double-cationic
      metals inside supermetallocyclophane (super[6]phane) cages. The heterolytic and
      homolytic associations show preferences for different metals, and new metal
      containing cages are proposed that should be viable candidates for synthesis.

PMID- 22986619
TI  - Self-priming compartmentalization digital LAMP for point-of-care.
AB  - Digital nucleic acid amplification provides unprecedented opportunities for
      absolute nucleic acid quantification by counting of single molecules. This
      technique is useful for molecular genetic analysis in cancer, stem cell,
      bacterial, non-invasive prenatal diagnosis in which many biologists are
      interested. This paper describes a self-priming compartmentalization (SPC)
      microfluidic chip platform for performing digital loop-mediated amplification
      (LAMP). The energy for the pumping is pre-stored in the degassed bulk PDMS by
      exploiting the high gas solubility of PDMS; therefore, no additional structures
      other than channels and reservoirs are required. The sample and oil are
      sequentially sucked into the channels, and the pressure difference of gas
      dissolved in PDMS allows sample self-compartmentalization without the need for
      further chip manipulation such as with pneumatic microvalves and control systems,
      and so on. The SPC digital LAMP chip can be used like a 384-well plate, so, the
      world-to-chip fluidic interconnections are avoided. The microfluidic chip
      contains 4 separate panels, each panel contains 1200 independent 6 nL chambers
      and can be used to detect 4 samples simultaneously. Digital LAMP on the
      microfluidic chip was tested quantitatively by using beta-actin DNA from humans.
      The self-priming compartmentalization behavior is roughly predictable using a two
      dimensional model. The uniformity of compartmentalization was analyzed by
      fluorescent intensity and fraction of volume. The results showed that the
      feasibility and flexibility of the microfluidic chip platform for amplifying
      single nucleic acid molecules in different chambers made by diluting and
      distributing sample solutions. The SPC chip has the potential to meet the
      requirements of a general laboratory: power-free, valve-free, operating at
      isothermal temperature, inexpensive, sensitive, economizing labour time and
      reagents. The disposable analytical devices with appropriate air-tight packaging
      should be useful for point-of-care, and enabling it to become one of the common
      tools for biology research, especially, in point-of-care testing.

PMID- 22986620
TI  - Towards resolution of the Fermi surface in underdoped high-Tc superconductors.
AB  - We survey recent experimental results including quantum oscillations and
      complementary measurements probing the electronic structure of underdoped
      cuprates, and theoretical proposals to explain them. We discuss quantum
      oscillations measured at high magnetic fields in the underdoped cuprates that
      reveal a small Fermi surface section, comprising quasiparticles that obey Fermi
      Dirac statistics, unaccompanied by other states of comparable thermodynamic mass
      at the Fermi level. The location of the observed Fermi surface section at the
      nodes is indicated by a body of evidence including the collapse in Fermi velocity
      measured by quantum oscillations, which is found to be associated with the nodal
      density of states observed in angular resolved photoemission, the persistence of
      quantum oscillations down to low fields in the vortex state, the small value of
      density of states from heat capacity and the multiple frequency quantum
      oscillation pattern consistent with nodal magnetic breakdown of bilayer-split
      pockets. A nodal Fermi surface pocket is further consistent with the observation
      of a density of states at the Fermi level concentrated at the nodes in
      photoemission experiments, and the antinodal pseudogap observed by photoemission,
      optical conductivity, nuclear magnetic resonance (NMR) Knight shift, as well as
      other complementary diffraction, transport and thermodynamic measurements. One of
      the possibilities considered is that the small Fermi surface pockets observed at
      high magnetic fields can be understood in terms of Fermi surface reconstruction
      by a form of small wavevector charge order, observed over long lengthscales in
      experiments such as NMR and x-ray scattering, potentially accompanied by an
      additional mechanism to gap the antinodal density of states.

PMID- 22986621
TI  - Cisplatin-docetaxel induction plus concurrent 3-D conformal radiotherapy and
      weekly chemotherapy for locally advanced non-small cell lung cancer patients: a
      phase II trial.
AB  - Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable
      locally advanced stage III non-small cell lung cancer. However, the optimal
      combination remains unclear. The aim of this study was to evaluate the efficacy
      of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m(2) and
      cisplatin 75 mg/m(2) followed by concurrent chemotherapy (weekly docetaxel
      cisplatin, 20 mg/m(2)) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5
      fractions per week/2 Gy per fraction). The primary endpoint was the response
      rate. Secondary objectives were toxicity, time to progression, and overall
      survival. Forty-four patients were included and 40 were eligible. The mean age
      was 60.5 years (range 40.7-72.1), and 75% had stage IIIB disease. Six patients
      underwent complete R0 resection including 2 pathologic complete responses after a
      planned intermediate evaluation. Thirty-three patients completed CHRT. The
      objective response rate was 65% (95% CI 50.2-79.8). Grade 3-4 hematologic and
      digestive toxicities were observed mainly during the induction phase. Grade 3
      esophagitis (5%) was experienced during CHRT. With a median follow-up of 38.7
      months, the median progression-free survival was 28.3 months (95% CI 11.0-35.0)
      and the median survival rate was 31.4 months. Cisplatin-docetaxel induction
      followed by concurrent 3-D conformal radiotherapy and weekly chemotherapy is a
      feasible protocol associated with a promising response rate and acceptable
      toxicity.

PMID- 22986622
TI  - Biological effect monitoring in peripheral blood lymphocytes from subjects
      occupationally exposed to antineoplastic drugs: assessment of micronuclei
      frequency.
AB  - OBJECTIVES: Antineoplastic drugs (ANPDs) are widely used in the treatment of
      cancer and some nonneoplastic diseases. However, most if not all of these
      chemical agents are generally nonselective and, along with tumor cells, normal
      cells may undergo cytotoxic/genotoxic damage. Italian pharmacists and nurses
      occupationally exposed to ANPDs during their normal work routines were monitored
      to evaluate biological effects (i.e., cytogenetic damage) eventually associated
      with exposure. The subjects were also monitored for primary, oxidative and
      excision repaired DNA damage as evaluated by comet assay (published data). In the
      present paper, we present the results obtained with the cytokinesis-block
      micronucleus (CBMN) test. METHODS: The CBMN test in peripheral blood lymphocytes
      was applied because of its ability to detect both clastogenic and aneugenic
      effects, and because it has recently been reported that micronuclei (MNs) are
      predictive of cancer risk in human populations. In this study, the evaluation of
      MN frequency was carried out using the CBMN test in the absence or in the
      presence of the DNA repair inhibitor Ara-C (cytosine arabinoside). RESULTS: No
      significant difference was observed for MN frequency comparing nurses handling
      ANPDs (exposed subjects) and controls; no correlations were found between job
      seniority, age, smoking habits and MN rates. CONCLUSIONS: Concerning the aim of
      this study to evaluate the genotoxic risk arising from occupational exposure to
      ANPDs, statistically significant differences in MN rates in the subjects under
      study could not be determined.

PMID- 22986623
TI  - Resurgent-like currents in mouse vas deferens myocytes are mediated by NaV1.6
      voltage-gated sodium channels.
AB  - Patch-clamp experiments were performed to investigate the molecular properties of
      resurgent-like currents in single smooth muscle cells dispersed from mouse vas
      deferens, utilizing both Na(V)1.6-null mice (Na(V)1.6(-/-)), lacking the
      expression of the Scn8a Na(+) channel gene, and their wild-type littermates
      (Na(V)1.6(+/+)). Na(V)1.6 immunoreactivity was clearly visible in dispersed
      smooth muscle cells obtained from Na(V)1.6(+/+), but not Na(V)1.6(-/-), vas
      deferens. Following a depolarization to +30 mV from a holding potential of -70 mV
      (to produce maximal inactivation of the Na(+) current), repolarization to
      voltages between -60 and +20 mV elicited a tetrodotoxin (TTX)-sensitive inward
      current in Na(V)1.6(+/+), but not Na(V)1.6(-/-), vas deferens myocytes. The
      resurgent-like current in Na(V)1.6(+/+) vas deferens myocytes peaked at
      approximately -20 mV in the current-voltage relationship. The peak amplitude of
      the resurgent-like current remained at a constant level when the membrane
      potential was repolarized to -20 mV following the application of depolarizing
      rectangular pulses to more positive potentials than +20 mV. 4,9
      Anhydrotetrodotoxin (4,9-anhydroTTX), a selective Na(V)1.6 blocking toxin,
      purified from a crude mixture of TTX analogues by LC-FLD techniques, reversibly
      suppressed the resurgent-like currents. beta-Pompilidotoxin, a voltage-gated
      Na(+) channel activator, evoked sustained resurgent-like currents in
      Na(V)1.6(+/+) but not Na(V)1.6(-/-) murine vas deferens myocytes. These results
      strongly indicate that, primarily, resurgent-like currents are generated as a
      result of Na(V)1.6 channel activity.

PMID- 22986624
TI  - Child maltreatment, dating perpetration of physical assault, and cortisol
      reactivity among disadvantaged female adolescents.
AB  - OBJECTIVE: Few studies have examined hypothalamic-pituitary-adrenal axis stress
      reactivity and its relationship to histories of child maltreatment and physical
      aggression. We examined the relation of a history of childhood sexual abuse (CSA)
      and perpetration of dating violence to patterns of cortisol change before
      (resting) and after (reactivity) exposure to a laboratory stressor. METHODS: In a
      sample of 40 disadvantaged sexually active female adolescent patients (ages 14-17
      years), we collected self-reports of lifetime child maltreatment (5 types) and
      past-year female perpetration of physical assault (PA) acts toward a romantic
      partner. We assessed changes in salivary cortisol trajectories during resting and
      reactivity phases following the viewing of a teen dating violence vignette.
      RESULTS: Reports of CSA (CSA+ group) were associated with reports of perpetration
      of severe dating PA (PA+ group), but the relation of these reports to laboratory
      assessed patterns of cortisol changes following the stressor was opposite. As
      compared with subjects without victimization or perpetration histories (referent
      group), the CSA+ group showed the most pronounced positive slope (reactivity),
      whereas the PA+ group showed the least positive slope following the laboratory
      stressor after the overlap between these groups was statistically adjusted. While
      showing less reactivity to the laboratory stressor, the PA+ group had higher
      levels of resting cortisol, which stayed high during reactivity as compared to
      the referent group. CONCLUSION: The laboratory paradigm to elicit neuroendocrine
      stress-related cortisol reactivity appears to be a promising tool for identifying
      altered cortisol physiology among female adolescents with mixed histories of CSA
      and perpetration of dating PA.

PMID- 22986625
TI  - Vitamin D status and changes in cardiovascular risk factors: a prospective study
      of a general population.
AB  - OBJECTIVES: A low vitamin D level has been associated with increased
      cardiovascular disease risk but possible mechanisms remain unclear. We
      investigated the association between vitamin D levels and 5-year changes in blood
      pressure, lipid profile and incidence of the metabolic syndrome, hypertension and
      hypercholesterolemia. METHODS: A random sample of 6,784 individuals aged 30-60
      years from a general population was investigated in the Inter99 study in 1999
      2001. Vitamin D (serum 25-hydroxyvitamin D) was measured at baseline by high
      performance liquid chromatography, and 4,330 individuals participated at the 5
      year follow-up and were included in the present study. RESULTS: The median
      baseline vitamin D concentration was 48.0 nmol/l. In multivariable linear
      regression analyses, a 10 nmol/l higher baseline level of vitamin D was
      associated with a decrease in triglycerides and very low density lipoprotein
      cholesterol by 0.52 (p = 0.03) and 0.66% (p = 0.005), respectively. In
      multivariable logistic regression analyses, the odds ratios per 10 nmol/l higher
      baseline vitamin D level were 0.95 (p < 0.05) and 0.94 (p = 0.01) for the
      development of the metabolic syndrome and hypercholesterolemia, respectively.
      There was no association between vitamin D and blood pressure. CONCLUSIONS: An
      optimal vitamin D status may influence cardiovascular health by changing the
      lipid profile in a favorable direction and decreasing the incidence of the
      metabolic syndrome.

PMID- 22986626
TI  - [Hydrocephalus in childhood : causes and imaging patterns].
AB  - CLINICAL ISSUE: Causes and imaging patterns of hydrocephalus differ depending on
      the age of the patient. Traditionally, hydrocephalus was classified into non
      communicating and communicating hydrocephalus but more recent classifications
      also take the site of occlusion and the etiology into account. DIAGNOSTICS: For
      the diagnostic work-up computed tomography (CT), sonography and magnetic
      resonance imaging (MRI) are available and MRI is the method of choice for
      children and adolescents as it allows determination of the cause and location of
      a possible obstruction. In the first 12-18 months sonography allows evaluation of
      the lateral ventricles and the third ventricle and CT is usually only chosen in
      children in emergency situations and/or if no other modality is available.
      PERFORMANCE: We retrospectively evaluated a population of 785 children and
      adolescents (426 males aged 0-17 years) referred for MRI between April 2009 and
      March 2012 due to headaches, somnolence, concentration difficulties or
      developmental delay. Among these 80 (49 male) met the MRI criteria for
      hydrocephalus, 75 (46 male) had non-communicating hydrocephalus and 5 (3 male)
      communicating hydrocephalus. Of the patients 24 (15 male) had posthemorrhagic
      aqueductal stenosis, 16 (8 male) intracranial tumors, 9 (6 male) Chiari II
      malformations, 5 (4 male) other congenital malformations including malformations
      of the Dandy Walker spectrum, 9 (3 male) idiopathic aqueductal stenosis, 7 (5
      male) arachnoidal cysts and 10 (8 male) other disorders, such as post-infections,
      macrocephaly cutis marmorata telangiectatica congenita (M-CMTC) syndrome,
      mesencephalic arteriovenous malformation (AVM), Langerhans cell histiocystosis.
      PRACTICAL RECOMMENDATIONS: It is important to take the age of the patient and the
      imaging pattern into account and to exclude tumors when reporting MR images of
      children with hydrocephalus.

PMID- 22986627
TI  - [Hydrocephalus and intracranial hypotension].
AB  - Ventricular enlargement due to a imbalance of the production of cerebrospinal
      fluid and its absorption can be a symptom of a variety of diseases. The causes
      are increased production or decreased absorption of cerebrospinal fluid and
      obstructions to cerebrospinal fluid flow. Treatment requires thorough
      neuroradiological imaging with high-resolution thin-section magnetic resonance
      imaging (MRI) and cerebrospinal fluid flow measurements. Thus, for instance even
      small membranes causing aqueductal obstruction can be detected and their
      influence on cerebrospinal fluid flow can be analyzed. The results of
      neurosurgical therapy, such as ventriculostomy can also be evaluated. This
      article provides an overview about imaging features as well as clinical and
      therapeutic aspects of hydrocephalus.

PMID- 22986628
TI  - [BDR releases].

PMID- 22986629
TI  - Is international volunteer surgery for cleft lip and cleft palate a cost
      effective and justifiable intervention? A case study from East Asia.
AB  - BACKGROUND: Although surgery provided by international volunteers is increasingly
      common in the developing world, there have been few assessments of the cost
      effectiveness of these activities. In this context, this study covered 15 years
      of experience of one international nongovernmental organization, Smile for
      Children, in providing cleft lip (CL) and cleft palate (CP) surgical services in
      Vietnam. METHODS: We analyzed the cost-effectiveness of the program and its
      contributions to building local capacity. To assess the cost-effectiveness of
      CL/CP surgery performed during Smile for Children's missions in Vietnam, we
      analyzed the data from four annual missions, from 2007 to 2010. According to the
      2003 World Health Organization Guide to Cost-Effectiveness Analysis, we
      calculated cost per disability-adjusted life years (DALYs) averted with and
      without age weighting. For the data from the 2010 mission, we repeated the same
      calculation but with and without considering opportunity cost for labor. RESULTS:
      The discounted cost per DALY averted averaged $68, ranging from $52 to $79
      depending on the year of the mission. The average discounted cost per DALY
      averted with age weighting was $56 (range $43-$65). For the calculation that
      takes into account the volunteers' possible income loss as the labor cost of the
      mission in 2010, the cost per DALY averted without age weighting increased by
      28%, from $76 to $97; and the cost per DALY averted with age weighting increased
      by 27%, from $63 to $80. Under all of these varying assumptions, the CL/CP
      program operated by Smile for Children is a cost-effective intervention using
      international criteria for cost-effectiveness. CONCLUSIONS: The contribution of
      the international volunteer surgical team to building in-country capacity is
      notable. It was achieved primarily through training Vietnamese surgeons during
      the mission trips and through sending these surgeons to Korea for training. Other
      staff, including anesthesiologists, were also trained; and equipment and supplies
      were provided.

PMID- 22986630
TI  - Ratio of cesarean deliveries to total operations and surgeon nationality are
      potential proxies for surgical capacity in central Haiti.
AB  - BACKGROUND: The World Health Organization has a standardized tool to assess
      surgical capacity in low- and middle-income countries (LMICs), but it is often
      resource- and time-intensive. There currently exists no simple, evidence-based
      measure of surgical capacity in these settings. The proportion of cesarean
      deliveries in regard to the total operations (C/O ratio) has been suggested as a
      way to assess quickly the capacity for emergency and essential surgery in LMICs.
      This ratio has been estimated to be between 23.3 and 41.5 % in LMICs, but the
      tool's utility has not been replicated. METHODS: We reviewed operative logbooks
      for the Partners In Health/Zanmi Lasante hospital in Cange, Haiti. We recorded
      data on all consecutive surgical patients from July 2008 to 2010 and calculated
      the C/O ratio by dividing the number of cesarean deliveries by the total number
      of operations performed. We also analyzed surgical data by surgeon nationality to
      provide additional information about local surgical capacity. RESULTS: A total of
      3,641 operations were performed between 2008 and 2010. The C/O ratio decreased
      significantly between 2008-2009 and 2009-2010 (13.4 vs. 10.7 %, p = 0.001) as the
      surgical volume and resources increased. Nationality analysis demonstrated that
      Haitian surgeons were able to provide a spectrum of general and specialist
      surgical care. CONCLUSIONS: In its inherent relation to essential surgical
      procedures and to the overall rate of cesarean deliveries in the region, the C/O
      ratio can provide an accessible assessment of regional surgical resources. In
      Haiti, the change in the C/O ratio demonstrated a relative increase in surgical
      capacity from 2008 to 2010. An additional analysis of surgeon nationality ensured
      that C/O ratio estimates more accurately reflect local practitioner activity, but
      deficiencies in the regional capacity to address the local burden of surgical
      disease may still exist.

PMID- 22986631
TI  - Toll-like receptor 3 activation differentially regulates phagocytosis of bacteria
      and apoptotic neutrophils by mouse peritoneal macrophages.
AB  - Toll-like receptor (TLR) activation by microbial pathogens triggers inflammatory
      responses against microbes. The phagocytic clearance of invading microbes and
      apoptotic immune cells is essential to resolve inflammation. However, the
      relationship between TLR activation and phagocytosis is poorly understood. We
      found that TLR3 activation promotes bacterial uptake through the activation of
      interferon-regulating factor 3 (IRF3) and inhibits phagocytosis of apoptotic
      neutrophils through the activation of nuclear factor-kappaB (NF-kappaB) by mouse
      peritoneal macrophages. The TLR signals that regulate the phagocytic ability of
      macrophages were also induced by TLR4 and TLR5 activation. Further, we
      demonstrated that TLR-induced tumor necrosis factor-alpha and interferon-beta
      contributed to the differential phagocytosis of apoptotic neutrophils and
      bacteria by macrophages. Moreover, activation of IRF3 upregulated the expression
      of some receptors involved in bacterial uptake, whereas activation of NF-kappaB
      downregulated the expression of molecules that facilitate the phagocytosis of
      apoptotic cells. These results describe an effect of TLR-triggered innate
      immunity on the phagocytic activity of macrophages.

PMID- 22986632
TI  - Computational discovery of putative quorum sensing inhibitors against LasR and
      RhlR receptor proteins of Pseudomonas aeruginosa.
AB  - Drugs have been discovered in the past mainly either by identification of active
      components from traditional remedies or by unpredicted discovery. A key
      motivation for the study of structure based virtual screening is the exploitation
      of such information to design targeted drugs. In this study, structure based
      virtual screening was used in search for putative quorum sensing inhibitors (QSI)
      of Pseudomonas aeruginosa. The virtual screening programme Glide version 5.5 was
      applied to screen 1,920 natural compounds/drugs against LasR and RhlR receptor
      proteins of P. aeruginosa. Based on the results of in silico docking analysis,
      five top ranking compounds namely rosmarinic acid, naringin, chlorogenic acid,
      morin and mangiferin were subjected to in vitro bioassays against laboratory
      strain PAO1 and two more antibiotic resistant clinical isolates, P. aeruginosa
      AS1 (GU447237) and P. aeruginosa AS2 (GU447238). Among the five compounds
      studied, except mangiferin other four compounds showed significant inhibition in
      the production of protease, elastase and hemolysin. Further, all the five
      compounds potentially inhibited the biofilm related behaviours. This interaction
      study provided promising ligands to inhibit the quorum sensing (QS) mediated
      virulence factors production in P. aeruginosa.

PMID- 22986633
TI  - Computation of relative binding free energy for an inhibitor and its analogs
      binding with Erk kinase using thermodynamic integration MD simulation.
AB  - In the present study, we carried out thermodynamic integration molecular dynamics
      simulation for a pair of analogous inhibitors binding with Erk kinase to
      investigate how computation performs in reproducing the relative binding free
      energy. The computation with BCC-AM1 charges for ligands gave -1.1 kcal/mol,
      deviated from experimental value of -2.3 kcal/mol by 1.2 kcal/mol, in good
      agreement with experimental result. The error of computed value was estimated to
      be 0.5 kcal/mol. To obtain convergence, switching vdw interaction on and off
      required approximately 10 times more CPU time than switching charges. Residue
      based contributions and hydrogen bonding were analyzed and discussed.
      Furthermore, subsequent simulation using RESP charge for ligand gave DeltaDeltaG
      of -1.6 kcal/mol. The computed results are better than the result of -5.6
      kcal/mol estimated using PBSA method in a previous study. Based on these results,
      we further carried out computations to predict DeltaDeltaG for five new analogs,
      focusing on placing polar and nonpolar functional groups at the meta site of
      benzene ring shown in the Fig. 1, to see if these ligands have better binding
      affinity than the above ligands. The computations resulted that a ligand with
      polar -OH group has better binding affinity than the previous examined ligand by
      ~2.0 kcal/mol and two other ligands have better affinity by ~1.0 kcal/mol. The
      predicted better inhibitors of this kind should be of interest to experimentalist
      for future experimental enzyme and/or cell assays.

PMID- 22986634
TI  - Dermoscopy of squamous cell carcinoma and keratoacanthoma.
AB  - OBJECTIVES To characterize dermoscopic criteria of squamous cell carcinoma (SCC)
      and keratoacanthoma and to compare them with other lesions. DESIGN Observer
      masked study of consecutive lesions performed from March 1 through December 31,
      2011. SETTING Primary care skin cancer practice in Brisbane, Australia.
      PARTICIPANTS A total of 186 patients with 206 lesions. MAIN OUTCOME MEASURES
      Sensitivity, specificity, predictive values, and odds ratios. RESULTS In a
      retrospective analysis of 60 invasive SCC and 43 keratoacanthoma cases, keratin,
      surface scale, blood spots, white structureless zones, white circles, and coiled
      vessels were commonly found in both types of lesions. We reevaluated the
      significance of these criteria in 206 raised, nonpigmented lesions (32 SCCs, 29
      keratoacanthomas, and 145 other lesions). Central keratin was more common in
      keratoacanthoma than in SCC (51.2% vs 30.0%, P = .03). Keratin had the highest
      sensitivity for keratoacanthoma and SCC (79%), and white circles had the highest
      specificity (87%). When keratoacanthoma and SCC were contrasted with basal cell
      carcinoma, the positive predictive values of keratin and white circles were 92%
      and 89%, respectively. When SCC and keratoacanthoma were contrasted with actinic
      keratosis and Bowen disease, the positive predictive value of keratin was 50% and
      that of white circles was 92%. In a multivariate model, white circles, keratin,
      and blood spots were independent predictors of SCC and keratoacanthoma. White
      circles had the highest odds ratio in favor of SCC and keratoacanthoma. The
      interobserver agreement for white circles was good (0.55; 95% CI, 0.44-0.65).
      CONCLUSIONS White circles, keratin, and blood spots are useful clues to
      differentiate SCC and keratoacanthoma from other raised nonpigmented skin lesions
      by dermoscopy. The significance of these criteria depends on the clinical
      context.

PMID- 22986635
TI  - Sprouting angiogenesis in human midterm uterus and fallopian tube is guided by
      endothelial tip cells.
AB  - Five samples of human midterm fetal uterus and fallopian tube (four donor bodies)
      were used to assess whether or not processes of angiogenesis are guided by
      endothelial tip cells (ETCs), and if cytokine-receptors, such as CD117/c-kit and
      PDGFR-alpha, are expressed in the microenvironment of the endothelial tubes. CD34
      labeled microvessels in the uterine wall (myometrium and endometrium) and in the
      wall of the uterine (fallopian) tube, and accurately identified ETCs in both
      organs. We conclude that sprouting angiogenesis in the developing human female
      tract is guided by ETCs. Moreover, CD117/c-kit antibodies labeled mural networks
      of pericytes, alpha-SMA-positive and desmin-negative, related to the endometrial
      (but not myometrial) microvessels, and similar labeling was identified in the
      wall of the uterine tube. PDGFR-alpha positive labeling, stromal and pericytary,
      was also found. Thus, sprouting angiogenesis in human fetal genital organs
      appears to be guided by tip cells and is influenced by tyrosine kinase receptor
      signaling.

PMID- 22986636
TI  - Differential diagnosis of infundibular dilation versus a small aneurysm of the
      internal carotid artery: assessment by three-dimensional rotational angiography
      with volume rendering.
AB  - We report our findings associated with the differential diagnosis of infundibular
      dilation (ID) versus a small intracranial aneurysm using three-dimensional
      rotational angiography with volume rendering (3DRA + VR). Angiographic findings
      associated with IDs found via two-dimensional digital subtraction angiography (2D
      DSA) or 3DRA + VR were reviewed for 138 consecutive patients with known or
      suspected aneurysms. Two readers independently evaluated the results of 2D-DSA
      and 3DRA + VR according to the same diagnostic criteria. We also evaluated the
      ability of 3D-DSA to show the spatial relation between IDs and anterior choroidal
      (AchA)/posterior communicating (PcomA) arteries. 2D-DSA and 3DRA + VR found 41
      and 48 IDs, respectively. 2D-DSA missed five AchA and two PcomA IDs. 2D-DSA was
      significantly inferior to 3DRA + VR for displaying the spatial relation between
      IDs and AchA/PcomA (P = 0). Thus, 3DRA + VR provides more useful information for
      distinguishing IDs from aneurysms. The superiority of 3DRA + VR might be because
      of its ability to display the spatial relation between IDs and AchA/PcomA.

PMID- 22986637
TI  - Pneumothorax after needle electromyography of the diaphragm: a case report.

PMID- 22986638
TI  - Cognitive mapping in persons newly diagnosed with type 2 diabetes.
AB  - PURPOSE: The purpose of this study was to determine the issues and perceptions of
      persons newly diagnosed (within last 3 months) with type 2 diabetes. METHODS: In
      this qualitative study, 16 adults newly diagnosed with type 2 diabetes were
      recruited, who completed a demographic, lifestyle, and diabetes management
      questionnaire and then were interviewed using cognitive mapping. Participants
      were asked to write words or phrases that came to mind when thinking about living
      with diabetes. From these words, common concepts were identified, grouped into
      clusters, and reduced into categories. Associations were sought between
      demographics and categories. RESULTS: A total of 260 Post-It notes were written,
      from which 123 concepts were identified and grouped into 24 clusters. The most
      frequent concept was eat, and the 3 most frequent clusters were food, negative
      emotions, and diabetes and its complications. The 9 categories, in order of
      frequency, were as follows: (1) need to (self-management), (2) concerns, (3) "I'm
      sick", (4) emotional distress, (5) loss, (6) the no's (limitations), (7) fears
      and complications, (8) have to (medical management), and (9) coping. Persons with
      a college education and a later interview date since diagnosis were associated
      with the concepts in the need to and have to categories. Concepts in the I'm sick
      category were associated with lower income and Hispanic ethnicity. CONCLUSIONS:
      Diabetes educators should consider this holistic representation of the issues and
      perceptions reflected in the common concepts, clusters, and categories expressed
      by persons newly diagnosed with diabetes.

PMID- 22986639
TI  - Blinded evaluation of interrater reliability of an operative competency
      assessment tool for direct laryngoscopy and rigid bronchoscopy.
AB  - OBJECTIVES To confirm interrater reliability using blinded evaluation of a skills
      assessment instrument to assess the surgical performance of resident and fellow
      trainees performing pediatric direct laryngoscopy and rigid bronchoscopy in
      simulated models. DESIGN Prospective, paired, blinded observational validation
      study. SUBJECTS Paired observers from multiple institutions simultaneously
      evaluated residents and fellows who were performing surgery in an animal
      laboratory or using high-fidelity manikins. The evaluators had no previous
      affiliation with the residents and fellows and did not know their year of
      training. INTERVENTIONS One- and 2-page versions of an objective structured
      assessment of technical skills (OSATS) assessment instrument composed of global
      and a task-specific surgical items were used to evaluate surgical performance.
      RESULTS Fifty-two evaluations were completed by 17 attending evaluators. The
      instrument agreement for the 2-page assessment was 71.4% when measured as a
      binary variable (ie, competent vs not competent) (kappa = 0.38; P = .08).
      Evaluation as a continuous variable revealed a 42.9% percentage agreement (kappa
      = 0.18; P = .14). The intraclass correlation was 0.53, considered
      substantial/good interrater reliability (69% reliable). For the 1-page
      instrument, agreement was 77.4% when measured as a binary variable (kappa = 0.53,
      P = .0015). Agreement when evaluated as a continuous measure was 71.0% (kappa =
      0.54, P < .001). The intraclass correlation was 0.73, considered high interrater
      reliability (85% reliable). CONCLUSIONS The OSATS assessment instrument is an
      effective tool for evaluating surgical performance among trainees with acceptable
      interrater reliability in a simulator setting. Reliability was good for both the
      1- and 2-page OSATS checklists, and both serve as excellent tools to provide
      immediate formative feedback on operational competency.

PMID- 22986640
TI  - First-principles study of lithium ion migration in lithium transition metal
      oxides with spinel structure.
AB  - The migration of lithium (Li) ions in electrode materials is an important factor
      affecting the rate performance of rechargeable Li ion batteries. We have examined
      Li migration in spinels LiMn(2)O(4), LiCo(2)O(4), and LiCo(1/16)Mn(15/16)O(4) by
      means of first-principles calculations based on density functional theory (DFT).
      The results showed that the trajectory of the Li jump was straight between the
      two adjacent Li ions for all of the three spinel compounds. However, there were
      significant differences in the energy profiles and the Li jump path for
      LiMn(2)O(4) and LiCo(2)O(4). For LiMn(2)O(4) the highest energy barrier was in
      the middle of the two tetrahedral sites, or in the octahedral vacancy (16c). For
      LiCo(2)O(4) the lowest energy was around the octahedral 16c site and the energy
      barrier was located at the bottleneck sites. The difference in the energy profile
      for LiCo(2)O(4) stemmed from the charge disproportion of Co(3.5+) to
      Co(3+)/Co(4+) caused by a Li vacancy forming and jumping, which was not observed
      for LiMn(2)O(4). Charge disproportion successfully accounted for the faster Li
      migration mechanism observed in LiCo(1/16)Mn(15/16)O(4). Our computational
      results demonstrate the importance of the effect of charge distribution on the
      ion jump.

PMID- 22986641
TI  - Evaluating metal ion salts as acid hydrolase mimics: metal-assisted hydrolysis of
      phospholipids at lysosomal pH.
AB  - Niemann-Pick disease and drug-induced phospholipidosis are lysosomal storage
      disorders in which there is an excessive accumulation of sphingomyelin in
      cellular lysosomes. Here we have explored the possibility of developing metal
      based therapeutic agents to reverse phospholipid build-up through phosphate ester
      bond hydrolysis at lysosomal pH (~4.8). Towards this end, we have utilized a
      malachite green/molybdate-based colorimetric assay to quantitate the inorganic
      phosphate released upon the hydrolysis of sphingomyelin by twelve d- and f-block
      metal ion salts. In reactions conducted at 60  degrees C, the yields produced by
      the cerium(IV) complex Ce(NH(4))(2)(NO(3))(6) were superior. An Amplex((r)) Red
      based colorimetric assay and mass spectrometry were then employed to detect
      choline. The data consistently showed that Ce(IV) hydrolyzed sphingomyelin more
      efficiently at lysosomal pH: i.e., yields of choline and phosphate were 54 +/- 4
      and 22 +/- 5 % at pH ~ 4.8, compared to 8 +/- 1 and 5 +/- 2 % at pH ~ 7.2.
      Hydrolysis at 60  degrees C could be significantly increased by converting
      sphingomyelin vesicles to mixed lipid vesicles and mixed micelles of Triton X
      100. We then utilized cerium(IV) to cleave sphingomyelin at 37  degrees C (no
      Triton X-100). Although choline and phosphate levels were relatively low,
      hydrolysis continued to be considerably more efficient at lysosomal pH. A side by
      side comparison to phosphatidylcholine was then made. While the yields of choline
      and phosphate produced by phosphatylcholine were higher, the ratio of pH ~ 4.8
      hydrolysis to pH ~ 7.2 hydrolysis was usually more favorable for sphingomyelin
      (37 and 60  degrees C).

PMID- 22986642
TI  - Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic
      expression of ileal Paneth cell alpha-defensins.
AB  - Paneth cell alpha-defensins are antimicrobial peptides involved in the control of
      the intestinal microbiota and immunological homeostasis. In mice, they are
      encoded by multiple, highly homologous genes (Defa). The transcriptional activity
      of ileal Defa genes was studied in response to pharmacological and genetic
      perturbations of the intestinal environment of C57BL/6 mice. Defa gene
      transcription was sensitive to oral antibiotic administration suggesting that
      commensal microbes regulate Defa expression. Ileal microbiota analysis showed
      that decreased transcription of Defa genes correlated with depletion of
      Lactobacillus. Defa expression was partially restored in vivo by lactobacillus
      administration to antibiotic-treated mice. Defa transcripts were less abundant in
      ex vivo, microbiota-free intestinal explants but recovered after explant exposure
      to UV-killed bacteria, Toll-like receptor (TLR)-2 or TLR4 agonists. Genetic
      deficiency of several TLRs or MyD88 led to dramatic drops in Defa transcription
      in vivo. These results show that Paneth cell Defa genes are regulated by
      commensal bacteria through TLR-MyD88 signaling and provide a further
      understanding of the dysregulation of intestinal homeostasis that occurs as a
      result of imbalances in the populations of commensal bacteria.

PMID- 22986643
TI  - Spatial working memory impairment in subclinical hypothyroidism: an FMRI study.
AB  - OBJECTIVE: Using a block-designed BOLD-fMRI to explore the neural basis of
      spatial working memory impairment in patients with subclinical hypothyroidism
      (SCH) performing an n-back task. METHODS: Sixteen patients with SCH before and
      after being treated with levothyroxine (LT4) for 6 months and 16 matched
      euthyroid subjects were scanned by fMRI under the n-back task. RESULTS: The fMRI
      scan found that a neural network consisting of bilateral dorsolateral prefrontal
      cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor
      area/anterior cingulate cortex, bilateral parietal lobe (PA) and right caudate
      nucleus/thalamus was activated, with right hemisphere dominance. In euthyroid
      subjects, all these regions of interest (ROIs) showed load effect; however, only
      left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed
      the same effect in Pre-SCH patients. Furthermore, activation intensities of most
      ROIs (especially DLPFC and right PA) for Pre-SCH patients were lower than those
      in the euthyroid subjects (F <3.046, p > 0.062). Importantly, after a 6-month
      treatment with LT4, the load effect in SCH patients appeared the same as in the
      euthyroid subjects in all the ROIs (F >13.176, p < 0.0001). CONCLUSION: Our
      previous study shows that verbal working memory of SCH patients is impaired with
      abnormal activity in bilateral frontal areas. In this study, the results
      indicated that SCH patients may also have spatial working memory impairments, and
      the altered activities of right DLPFC and right posterior parietal lobe may be
      one of the underlying neural mechanisms. Most importantly, this study shows that
      LT4 replacement therapy can improve the memory impairment and reverse the altered
      neural activity network.

PMID- 22986644
TI  - On the complexity and dynamics of in vivo Cisplatin-DNA adduct formation using
      HPLC/ICP-MS.
AB  - In this work we present a methodology to measure the complex adduct spectrum
      caused by the interaction of Cisplatin with DNA. By using an optimized DNA
      digestion procedure we were able to show that the adduct spectrum in in vivo
      duplex DNA is much more complex than described so far. For the first time a high
      abundance of interstrand adducts has been detected by using HPLC/ESI-MS. These
      adducts could play a key role in the DNA repair mechanisms and the development of
      cellular resistance to Cisplatin. By species-unspecific isotope dilution analysis
      HPLC/ICP-MS measurements, we were able to study the kinetics of adduct formation.
      With these experiments we proved that after the initial formation of adducts a
      rearrangement occurs on the DNA-strands leading to significant changes in adduct
      patterns over time. Furthermore, the parameters of the species-unspecific isotope
      dilution analysis were optimized to allow measurements of specific adducts in the
      DNA of Cisplatin exposed cells.

PMID- 22986645
TI  - Associations of dietary iron intake with mortality from cardiovascular disease:
      the JACC study.
AB  - BACKGROUND: We investigated the relationship between dietary iron intake and
      mortality from cardiovascular disease (CVD) in a population-based sample of
      Japanese adults. METHODS: The study cohort consisted of 58 615 healthy Japanese
      (23 083 men and 35 532 women), aged between 40 and 79 years, who had no history
      of stroke, coronary heart disease (CHD), or cancer at baseline. Dietary iron
      intake was assessed at baseline by a validated food frequency questionnaire
      administered between 1988 and 1990 as part of the Japan Collaborative Cohort
      (JACC) Study. RESULTS: We documented 2690 (1343 men and 1347 women) deaths from
      CVD: 1227 (607 men and 620 women) deaths from total stroke, 651 from ischemic
      stroke (355 men and 296 women), 459 (196 men and 263 women) from hemorrhagic
      stroke, and 557 (311 men and 246 women) from CHD. Dietary intake of total iron
      was positively associated with mortality from total and ischemic stroke and total
      CVD in men. The multivariable hazard ratio for the highest versus the lowest
      quintile of total iron intake was 1.43 (95% CI, 1.02-2.00; P for trend = 0.009)
      for total stroke and 1.27 (1.01-1.58; 0.023) for total CVD in men. Dietary total
      iron intake was not associated with mortality from other endpoints in men, and
      was not associated with any endpoints in women. CONCLUSIONS: Dietary intake of
      total iron was positively associated with mortality from stroke and total CVD in
      Japanese men.

PMID- 22986646
TI  - Expression profile of fatty acid metabolism genes in preimplantation blastocysts
      of obese and non-obese mice.
AB  - BACKGROUND: Recent studies have disclosed a close relationship between maternal
      obesity, fetal metabolism and pre- and postnatal development. The lipid
      metabolism in preimplantation embryos is a possible target of metabolic
      programming. METHODS: 31 genes of beta-oxidation and fatty acid and cholesterol
      uptake, synthesis and regulation were analyzed in day 3.5 blastocysts from NZO
      (obese) and C57Bl/6 (normal weight) mice by RT-PCR and semiquantitative PCR.
      RESULTS: The most obvious difference between both strains was the lack of the RXR
      gamma transcript in NZO blastocysts. In adult NZO mice, RXR gamma is detectable
      in most tissues. In a semiquantitative analysis, a higher transcription rate of
      fatty acid transport protein 4 (p = 0.004) and a reduced transcript number of
      fatty acid synthase (p = 0.049) was found in NZO blastocysts. Cholesterol
      synthesis regulation was modified in NZO blastocysts, as indicated by the ratio
      of sterol regulatory element-binding protein (SREBP) 2 / insulin-induced gene 1
      (Insig 1) (p = 0.001). CONCLUSION: In mouse blastocysts enzymes and signal
      molecules of fatty acid and cholesterol metabolism resemble those expressed
      postnatally. Distinct differences in transcription rates of genes between
      blastocysts from obese and non-obese mothers indicate that preimplantation embryo
      development is an early target for metabolic programming.

PMID- 22986647
TI  - Nonalcoholic steatohepatitis in bariatric patients with a diagnosis of
      obstructive sleep apnea.
AB  - OBJECTIVE: To study a possible association between obstructive sleep apnea (OSA)
      severity, managed with noninvasive ventilation, and nonalcoholic steatohepatitis
      (NASH) in bariatric surgical patients. METHODS: Medical records of 218 bariatric
      surgical patients who underwent liver biopsy were reviewed. OSA severity was
      determined from preoperative polysomnography (apnea-hypopnea index (AHI) <= 15
      no/mild OSA vs. AHI >= 16 moderate/severe OSA). Patients diagnosed with OSA were
      prescribed noninvasive ventilation. Patients were categorized according to liver
      histopathology into 3 groups: (i) no liver disease or simple steatosis, (ii) mild
      NASH (steatosis with necroinflammation and mild fibrosis (stage 0-1)), and iii)
      advanced NASH (steatosis with necroinflammation and more advanced fibrosis (stage
      >= 2)). RESULTS: 125 patients (57%) had no/mild OSA, and 93 (43%) had
      moderate/severe OSA. There was no difference in serum aminotransferases between
      patients by OSA severity classification. There was a high prevalence of hepatic
      histopathological abnormalities: 84% patients had steatosis, 57% had
      necroinflammation, 34% had fibrotic changes, and 14% had advanced NASH. There was
      no association between severity of NASH and severity of OSA. CONCLUSIONS: There
      is no association between stage of steatohepatitis and OSA severity among
      morbidly obese patients managed with noninvasive ventilation.

PMID- 22986648
TI  - Benefits and environmental determinants of physical activity in children and
      adolescents.
AB  - In this review, we identify the health benefits associated with physical activity
      (PA); address the physical activity and sedentary guidelines issued by public
      health scientists as well as children's compliance to these guidelines; discuss
      the importance of motor skill acquisition during early childhood; and identify
      different settings that contribute to physical activity participation and
      strategies for improving PA in these settings. Results show that regular
      participation in PA during childhood has numerous immediate benefits, including
      positive changes in adiposity, skeletal health, psychological health, and
      cardiorespiratory fitness. Additionally, motor skill development during early
      childhood may have immediate health benefits as well as long-lasting effects in
      adulthood. Furthermore, the benefits of PA during childhood also appear to
      positively influence adult health outcomes, such as increased bone mineral
      density. Key environmental settings that have been shown to influence children's
      PA behavior include child care, active commuting to and from school, school
      recess, school physical education, after-school programs, churches, medical
      settings, and the home environment. Recommendations for practitioners and
      researchers are discussed.

PMID- 22986649
TI  - The renin-angiotensin system in the pathophysiology of type 2 diabetes.
AB  - Increased activation of the renin-angiotensin system (RAS) has been related to
      cardiovascular disease and type 2 diabetes mellitus. Most randomized clinical
      trials have demonstrated that RAS blockade reduces the incidence of type 2
      diabetes, which has been explained by improved insulin secretion and insulin
      sensitivity. In this review, an overview of the mechanisms that may underlie the
      association between the RAS and type 2 diabetes will be provided, with focus on
      skeletal muscle and adipose tissue function. This will include discussion of
      several human studies performed in our laboratory to investigate the metabolic
      and hemodynamic effects of the RAS, combining in vivo measurements of whole-body
      and tissue metabolism with molecular and immunohistochemical approaches.
      Available data suggest that the detrimental effects of the RAS on insulin
      secretion are mediated by a reduction in pancreatic blood flow and induction of
      islet fibrosis, oxidative stress as well as inflammation, whereas both impaired
      skeletal muscle function and adipose tissue dysfunction may underlie RAS-induced
      insulin resistance. Thus, although future studies in humans are warranted,
      current evidence supports that targeting the RAS in intervention studies may
      improve metabolic and cardiovascular function in conditions of insulin resistance
      like obesity and type 2 diabetes.

PMID- 22986650
TI  - Radiological patterns of the bony roof of the superior semicircular canal.
AB  - OBJECTIVES: To study the radiological patterns of the bony roof of the superior
      semicircular canal with a view for obtaining readily applicable conclusions.
      DESIGN: 84 patients (163 petrous bones) have been studied by Multi-slice Helical
      Computed tomography (Philips Brilliance 6). We have determined the distribution
      of the different types of bone cover of the superior semicircular canal, taking
      some previously notified, standardised measurements of normality as reference.
      RESULTS: During the analysis of the roof of the superior semicircular canal, we
      have distinguished five different types, depending on their thickness and
      tomodensitometric aspect. Normal pattern in 121 cases (74.2 %), with a thickness
      of between 0.6 and 1.7 mm, papyraceous pattern or fine thickness <=0.5 mm that
      appears in 23 of our cases (14.1 %), thick pattern >=1.8 mm that we have observed
      in 11 cases (6.7 %), and pneumatised pattern in 5 cases (3.1 %), which is
      characterised by having supralabyerinthine cells. Finally, a dehiscent pattern
      was observed in three cases (1.8 %). CONCLUSION: We describe five patterns of
      superior semicircular canal roofs: normal, thick, papyraceous, pneumatised and
      dehiscent. The papyraceous type and the dehiscent type would be subject to
      producing pathology, and in some cases the latter could be a consequence of the
      former.

PMID- 22986651
TI  - New anatomical data on the growing C4 vertebra and its three ossification centers
      in human fetuses.
AB  - PURPOSE: Detailed knowledge on the normative growth of the spine is of great
      relevance in the prenatal diagnosis of its abnormalities. The present study was
      conducted to compile age-specific reference data for vertebra C4 and its three
      ossification centers in human fetuses. MATERIALS AND METHODS: With the use of CT
      (Biograph mCT), digital image analysis (Osirix 3.9) and statistical analysis
      (Wilcoxon signed-rank test, Kolmogorov-Smirnov test, Levene's test, Student's t
      test, one-way ANOVA, post hoc RIR Tukey test, linear and nonlinear regression
      analysis), the normative growth of vertebra C4 and its three ossification centers
      in 55 spontaneously aborted human fetuses (27 males, 28 females) aged 17-30 weeks
      was examined. RESULTS: Significant differences in neither sex nor laterality were
      found. The height and transverse and sagittal diameters of the C4 vertebral body
      increased logarithmically as: y = -3.866 + 2.225 * ln(Age) +/- 0.238 (R(2) =
      0.69), y = -7.077 + 3.547 * ln(Age) +/- 0.356 (R(2) = 0.72) and y = -3.886 +
      2.272 * ln(Age) +/- 0.222 (R(2) = 0.73), respectively. The C4 vertebral body grew
      linearly in cross-sectional area as y = -7.205 + 0.812 * Age +/- 1.668 (R(2) =
      0.76) and four-degree polynomially in volume as y = 14.108 + 0.00007 * Age(4) +/-
      6.289 (R(2) = 0.83). The transverse and sagittal diameters, cross-sectional area
      and volume of the ossification center of the C4 vertebral body generated the
      following functions: y = -8.836 + 3.708 * ln(Age) +/- 0.334 (R(2) = 0.76), y = 
      7.748 + 3.240 * ln(Age) +/- 0.237 (R(2) = 0.83), y = -4.690 + 0.437 * Age +/-
      1.172 (R(2) = 0.63) and y = -5.917 + 0.582 * Age +/- 1.157 (R(2) = 0.77),
      respectively. The ossification center-to-vertebral body volume ratio gradually
      declined with age. On the right and left, the neural ossification centers showed
      the following growth: y = -19.601 + 8.018 * ln(Age) +/- 0.369 (R(2) = 0.92) and y
      = -15.804 + 6.912 * ln(Age) +/- 0.471 (R (2) = 0.85) for length, y = -5.806 +
      2.587 * ln(Age) +/- 0.146 (R(2) = 0.88) and y = -5.621 + 2.519 * ln(Age) +/-
      0.146 (R(2) = 0.88) for width, y = -9.188 + 0.856 * Age +/- 2.174 (R(2) = 0.67)
      and y = -7.570 + 0.768 * Age +/- 2.200 (R(2) = 0.60) for cross-sectional area,
      and y = -13.802 + 1.222 * Age +/- 1.872 (R(2) = 0.84) and y = -11.038 + 1.061 *
      Age +/- 1.964 (R(2) = 0.80) for volume, respectively. CONCLUSIONS: The
      morphometric parameters of vertebra C4 and its three ossification centers show no
      sex differences. The C4 vertebral body increases logarithmically in height and
      both sagittal and transverse diameters, linearly in cross-sectional area, and
      four-degree polynomially in volume. The three ossification centers of vertebra C4
      grow logarithmically in both transverse and sagittal diameters, and linearly in
      both cross-sectional area and volume. The age-specific reference intervals for
      evolving vertebra C4 may be useful in the prenatal diagnosis of congenital spinal
      defects.

PMID- 22986652
TI  - Steroids, oh steroids, my kingdom for some answers.

PMID- 22986653
TI  - Whom should we rely on when assessing symptoms of critically ill patients?

PMID- 22986654
TI  - beta-blockers: more good news?

PMID- 22986655
TI  - Addressing the national organ shortage with targeted donor management.

PMID- 22986656
TI  - The many facets of procalcitonin in the critically ill population.

PMID- 22986657
TI  - Sedation, nighttime, icebergs, and the Titanic.

PMID- 22986658
TI  - Beware of the Nottingham sheriff when manipulating cerebral blood flow in
      subarachnoid hemorrhage.

PMID- 22986659
TI  - Precardiac surgery angiotensin-converting enzymes and mineralocorticoid blockers
      do not trump atrial fibrillation but possibly acute kidney injury: the value of a
      negative randomized study.

PMID- 22986660
TI  - Broken hearts and transfusion-related acute lung injury.

PMID- 22986661
TI  - Expanding our thinking regarding early goal-directed therapy.

PMID- 22986662
TI  - Tetrahydrobiopterin (BH4) in septic shock: a key to solving the nitric oxide
      puzzle and opening the microcirculation?

PMID- 22986663
TI  - Ventilator-induced diaphragmatic vascular dysfunction.

PMID- 22986664
TI  - Continuously monitored bedside electroencephalogram in the intensive care unit
      after cardiac arrest: about time!

PMID- 22986665
TI  - What parents want: personalizing the approach to medical decision making.

PMID- 22986666
TI  - On balance, are fluids a marker or a target?

PMID- 22986667
TI  - Assessment of renal perfusion: advocacy for Doppler ultrasonography.

PMID- 22986669
TI  - Ultrasound-guided subclavian and axillary vein cannulation via an infraclavicular
      approach:  In the tradition of Robert Aubaniac.

PMID- 22986670
TI  - Hemodynamic treatment algorithms should follow physiology or they fail to improve
      outcome.

PMID- 22986672
TI  - Right ventricular function in mechanical ventilation: it is not just about size!

PMID- 22986674
TI  - With sepsis:  If fever is good, then hypothermia is bad!

PMID- 22986676
TI  - Current randomized clinical trials of red cell storage duration and patient
      outcomes.

PMID- 22986678
TI  - Arm hand skilled performance in persons with a cervical spinal cord injury--long
      term follow-up.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess development of arm
      hand skilled performance (AHSP) during and after in-patient rehabilitation in
      persons with cervical spinal cord injury (CSCI) and to determine factors that
      influence the outcome. SETTING: Eight rehabilitation centres in the Netherlands
      with specialised spinal cord injury departments. METHODS: AHSP was assessed using
      the Van Lieshout test (VLT) in persons admitted with recent CSCI. Assessment was
      carried out at the beginning (t1), after 3 months (t2), at the end (t3) of in
      patient rehabilitation, and 1 and 5 years thereafter (t4, t5). Multilevel
      regression analysis was performed to determine development of AHSP and
      associations between AHSP and age, gender, motor completeness, lesion level (high
      or low CSCI), motor scores of upper extremity (MSUE), and pain in the tested arm.
      RESULTS: Fifty-five participants were included with mean age 38 years (range 18
      64). There were 73% male, 80% had high CSCI (C3-C6) and 69% had motor complete
      lesion. Scores of VLT improved significantly during in-patient rehabilitation
      (mean: t1=25; t3=33) (P=0.005), scores remained unchanged at 1 year (t4=32) and 5
      years (t5=32) (P=0.903) after in-patient rehabilitation. Motor completeness, MSUE
      and pain were significantly related to the VLT score (P<0.001, P<0.001, P=0.015,
      respectively). Age, gender and lesion level had no significant relationship.
      CONCLUSION: AHSP improved during in-patient rehabilitation. It was then stable
      during the next 5 years after discharge. Persons with an incomplete lesion, high
      MSUE and no pain in the tested arm perform best on the VLT.

PMID- 22986679
TI  - Editorial Note on: Morbidity of urinary tract infection after urodynamic
      examination of hospitalized SCI patients: the impact of bladder management.

PMID- 22986680
TI  - Paramutagenicity of a p1 epiallele in maize.
AB  - Complex silencing mechanisms in plants and other kingdoms target transposons,
      repeat sequences, invasive viral nucleic acids and transgenes, but also
      endogenous genes and genes involved in paramutation. Paramutation occurs in a
      heterozygote when a transcriptionally active allele heritably adopts the
      epigenetic state of a transcriptionally and/or post-transcriptionally repressed
      allele. P1-rr and its silenced epiallele P1-pr, which encode a Myb-like
      transcription factor mediating pigmentation in floral organs of Zea mays, differ
      in their cytosine methylation pattern and chromatin structure at a complex
      enhancer site. Here, we tested whether P1-pr is able to heritably silence its
      transcriptionally active P1-rr allele in a heterozygote and whether DNA
      methylation is associated with the establishment and maintenance of P1-rr
      silencing. We found that P1-pr participates in paramutation as the repressing
      allele and P1-rr as the sensitive allele. Silencing of P1-rr is highly variable
      compared to the inducing P1-pr resulting in a wide range of gene expression.
      Whereas cytosine methylation at P1-rr is negatively correlated with transcription
      and pigment levels after segregation of P1-pr, methylation lags behind the
      establishment of the repressed p1 gene expression. We propose a model in which P1
      pr paramutation is triggered by changing epigenetic states of transposons
      immediately adjacent to a P1-rr enhancer sequence. Considering the vast amount of
      transposable elements in the maize genome close to regulatory elements of genes,
      numerous loci could undergo paramutation-induced allele silencing, which could
      also have a significant impact on breeding agronomically important traits.

PMID- 22986681
TI  - Morbid obesity rates continue to rise rapidly in the United States.
AB  - Clinically severe or morbid obesity (body mass index (BMI) >40 or 50 kg m(-2))
      entails far more serious health consequences than moderate obesity for patients,
      and creates additional challenges for providers. The paper provides time trends
      for extreme weight categories (BMI >40 and >50 kg m(-2)) until 2010, using data
      from the Behavioral Risk Factor Surveillance System. Between 2000 and 2010, the
      prevalence of a BMI >40 kg m(-2) (type III obesity), calculated from self
      reported height and weight, increased by 70%, whereas the prevalence of BMI >50
      kg m(-2) increased even faster. Although the BMI rates at every point in time are
      higher among Hispanics and Blacks, there were no significant differences in
      trends between them and non-Hispanic Whites. The growth rate appears to have
      slowed down since 2005. Adjusting for self-report biases, we estimate that in
      2010 15.5 million adult Americans or 6.6% of the population had an actual BMI >40
      kg m(-2). The prevalence of clinically severe obesity continues to be increasing,
      although less rapidly in more recent years than prior to 2005.

PMID- 22986682
TI  - Prospective cohort study of body mass index and the risk of hospitalisation:
      findings from 246361 participants in the 45 and Up Study.
AB  - OBJECTIVE: To quantify the risk of hospital admission in relation to fine
      increments in body mass index (BMI). DESIGN, SETTING, AND PARTICIPANTS:
      Population-based prospective cohort study of 246,361 individuals aged greater
      than or equal to 45 years, from New South Wales, Australia, recruited from 2006
      2009. Self-reported data on BMI and potential confounding/mediating factors were
      linked to hospital admission and death data. MAIN OUTCOMES: Cox-models were used
      to estimate the relative risk (RR) of incident all-cause and diagnosis-specific
      hospital admission (excluding same day) in relation to BMI. RESULTS: There were
      61,583 incident hospitalisations over 479,769 person-years (py) of observation.
      In men, hospitalisation rates were lowest for BMI 20-<25 kg m(-2) (age
      standardised rate: 120/1000 py) and in women for BMI 18.5-<25 kg m(-2) (102/1000
      py); above these levels, rates increased steadily with increasing BMI; rates were
      203 and 183/1000 py, for men and women with BMI 35-50 kg m(-2), respectively.
      This pattern was observed regardless of baseline health status, smoking status
      and physical activity levels. After adjustment, the RRs (95% confidence interval)
      per 1 kg m(-2) increase in BMI from >= 20 kg m(-2) were 1.04(1.03-1.04) for men
      and 1.04(1.04-1.05) for women aged 45-64; corresponding RRs for ages 65-79 were
      1.03(1.02-1.03) and 1.03(1.03-1.04); and for ages >= 80 years, 1.01(1.00-1.01)
      and 1.01(1.01-1.02). Hospitalisation risks were elevated for a large range of
      diagnoses, including a number of circulatory, digestive, musculoskeletal and
      respiratory diseases, while being protective for just two-fracture and hernia.
      CONCLUSIONS: Above normal BMI, the RR of hospitalisation increases with even
      small increases in BMI, less so in the elderly. Even a small downward shift in
      BMI, among those who are overweight not just those who are obese, could result in
      a substantial reduction in the risk of hospitalisation.

PMID- 22986683
TI  - Lack of evidence for high fructose corn syrup as the cause of the obesity
      epidemic.

PMID- 22986684
TI  - Body weight, fat distribution and colorectal cancer risk: a report from cohort
      studies of 134255 Chinese men and women.
AB  - OBJECTIVE: The objective was to evaluate the association of body size and fat
      distribution with the risk of colorectal cancer (CRC) in Chinese men and women.
      DESIGN: This was a population-based, prospective cohort study. SUBJECTS: The
      analysis included 134,255 Chinese adults enrolled in the Shanghai Women's Health
      Study and the Shanghai Men's Health Study, with an average follow-up of 11.0 and
      5.5 years, respectively. MEASUREMENTS: Waist circumference (WC), body mass index
      (BMI) and waist-to-hip ratio (WHR) were measured by trained interviewers at
      baseline. Multivariable Cox models were used to calculate adjusted hazard ratios
      (HRs) for incident CRC. RESULTS: A total of 935 incident CRC cases were
      identified. Both measures of general adiposity (measured by BMI) and central
      adiposity (measured by WHR and WC) were significantly associated with an
      increased risk of colon cancer in men but not in women. Multivariable-adjusted
      HRs for colon cancer in men in the highest compared with the lowest quintiles
      were 2.15 (95% confidence interval (CI): 1.35-3.43; P for trend=0.0006) for BMI,
      1.97 (95% CI: 1.19-3.24; P for trend=0.0004) for WHR and 2.00 (95% CI: 1.21-3.29;
      P for trend=0.0002) for WC. The BMI-associated risk was attenuated in analyses
      stratified by WHR, whereas the WHR-associated risk remained significant in the
      high BMI stratum (HR for comparison of extreme tertiles of WHR: 3.38, 95% CI:
      1.47-7.75; P for trend =0.0002). None of these anthropometric measures were
      significantly associated with rectal cancer. CONCLUSION: Obesity, particularly
      central obesity, was associated with an increased risk of colon cancer in men.

PMID- 22986685
TI  - Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte  differentiation.
AB  - Indole-3-carbinol (I3C), a natural product of Brassica vegetables such as
      broccoli and cabbage, inhibits proliferation and induces apoptosis in various
      cancer cells. I3C has recently received attention as a possible anti-obesity
      agent. However, how I3C interacts with specific targets in the pathways involved
      in obesity and metabolic disorders is unknown. Silent mating type information
      regulation 2 homolog 1 (SIRT1), a NADp-dependent deacetylase sirtuin, has
      recently emerged as a novel therapeutic target for metabolic diseases. Herein, we
      report that I3C is a potent, specific SIRT1 activator efficacious in cultured 3T3
      L1 cell lines. A pull-down assay showed that I3C binds to SIRT1. To assess the
      significance of this binding, we determined whether I3C could activate SIRT1
      deacetylase activity in a cell-free system. We found that I3C binds to SIRT1 and
      activates SIRT1 deacetylase activity in 3T3-L1 cells. In addition, I3C did not
      inhibit adipocyte differentiation in 3T3-L1 cells in which SIRT1 was knockdowned.
      Further, reverse transcriptase polymerase chain reaction analysis showed that I3C
      treatment reduced mRNA levels of adipogenic genes that encode for C/EBPa, PPARg2,
      FAS, and aP2 in 3T3-L1 cells but not in SIRT1 knockdown cells. Overall, these
      results suggested that I3C ameliorates adipogenesis by activating SIRT1 in 3T3-L1
      cells.

PMID- 22986686
TI  - Male gametogenesis and sterility in garlic (Allium sativum L.): barriers on the
      way to fertilization and seed production.
AB  - Commercial cultivars of garlic (Allium sativum) do not produce flowers and seed;
      hence, information on microgametogenesis and genetic knowledge of this important
      crop is unavailable. Recently, physiological studies enabled flowering and
      fertility restoration in garlic bolting genotypes by environmental manipulations,
      thus broadening of the genetic variation and facilitating genetic studies. The
      present report provides first detailed description of the development of male
      gametophytes in 11 garlic genotypes varying in their fertility traits.
      Morphological and anatomical studies revealed completely fertile genotypes, as
      well as variation in anther and pollen development and disruption of the male
      organs and gametes at different developmental stages. Three types of plant
      sterility were observed, including complete sterility, male sterility and
      environmentally induced male sterility. The ITS1 and ITS2 regions of rRNA of the
      studied genotypes proved to be strongly conservative and thus did not correspond
      with the phenotypic expression of fertility or sterility in garlic. On the other
      hand, two-dimensional protein separation maps revealed significant differences
      between fertile and sterile genotypes, as well as between developmental stages of
      microsporogenesis. Further research is needed to investigate the internal
      mechanisms and environmental component of garlic sterility, as well as the
      possible molecular markers of these traits.

PMID- 22986687
TI  - CING: an integrated residue-based structure validation program suite.
AB  - We present a suite of programs, named CING for Common Interface for NMR Structure
      Generation that provides for a residue-based, integrated validation of the
      structural NMR ensemble in conjunction with the experimental restraints and other
      input data. External validation programs and new internal validation routines
      compare the NMR-derived models with empirical data, measured chemical shifts,
      distance- and dihedral restraints and the results are visualized in a dynamic Web
      2.0 report. A red-orange-green score is used for residues and restraints to
      direct the user to those critiques that warrant further investigation. Overall
      green scores below ~20 % accompanied by red scores over ~50 % are strongly
      indicative of poorly modelled structures. The publically accessible, secure iCing
      webserver ( https://nmr.le.ac.uk ) allows individual users to upload the NMR data
      and run a CING validation analysis.

PMID- 22986688
TI  - NMR structure note: solution structure of human Miz-1 zinc fingers 8 to 10.

PMID- 22986690
TI  - Bullae after rapid blood transfusion through a warming system.

PMID- 22986689
TI  - Solid-state NMR analysis of membrane proteins and protein aggregates by proton
      detected spectroscopy.
AB  - Solid-state NMR has emerged as an important tool for structural biology and
      chemistry, capable of solving atomic-resolution structures for proteins in
      membrane-bound and aggregated states. Proton detection methods have been recently
      realized under fast magic-angle spinning conditions, providing large sensitivity
      enhancements for efficient examination of uniformly labeled proteins. The first
      and often most challenging step of protein structure determination by NMR is the
      site-specific resonance assignment. Here we demonstrate resonance assignments
      based on high-sensitivity proton-detected three-dimensional experiments for
      samples of different physical states, including a fully-protonated small protein
      (GB1, 6 kDa), a deuterated microcrystalline protein (DsbA, 21 kDa), a membrane
      protein (DsbB, 20 kDa) prepared in a lipid environment, and the extended core of
      a fibrillar protein (alpha-synuclein, 14 kDa). In our implementation of these
      experiments, including CONH, CO(CA)NH, CANH, CA(CO)NH, CBCANH, and CBCA(CO)NH,
      dipolar-based polarization transfer methods have been chosen for optimal
      efficiency for relatively high protonation levels (full protonation or 100 %
      amide proton), fast magic-angle spinning conditions (40 kHz) and moderate proton
      decoupling power levels. Each H-N pair correlates exclusively to either intra- or
      inter-residue carbons, but not both, to maximize spectral resolution. Experiment
      time can be reduced by at least a factor of 10 by using proton detection in
      comparison to carbon detection. These high-sensitivity experiments are especially
      important for membrane proteins, which often have rather low expression yield.
      Proton-detection based experiments are expected to play an important role in
      accelerating protein structure elucidation by solid-state NMR with the improved
      sensitivity and resolution.

PMID- 22986691
TI  - Gefitinib-induced paronychia: response to autologous platelet-rich plasma.
AB  - BACKGROUND: Paronychia has been reported in as many as 10% of patients treated
      with gefitinib. Although conservative management and treatment with topical or
      systemic antibiotics are beneficial, no effective method exists for intractable
      cases. Platelet-rich plasma (PRP)consists of a high concentration of platelets
      that promote wound healing through chemotaxis, cell proliferation,angiogenesis,
      and tissue remodeling. OBSERVATIONS: We herein report a refractory case of
      gefitinib-induced paronychia successfully treated with autologous PRP. A 68-year
      old woman who had been diagnosed as having lung adenocarcinoma with multiple bone
      and brain metastases initiated gefitinib therapy at an oral dose of 250 mg/d.
      After 1 month, multiple paronychia with periungual granulation appeared on the
      nailfold of the first, second, and third toenails of both feet.Because the
      paronychia recurred repeatedly despite use of a topical antibiotic, topical
      corticosteroid, and short term systemic antibiotic, she started PRP treatment.
      After 3 months, the lesion showed marked improvement with minimal pain or
      discharge. CONCLUSION: This case highlights the therapeutic challenges of using
      PRP to promote tissue repair in intractable gefitinib-induced paronychia and
      merits further investigation.

PMID- 22986692
TI  - Low-dose rate brachytherapy of the prostate in elderly patients.
AB  - PURPOSE: This study evaluated the biochemical diseasefree survival (bDFS) rate,
      overall survival rate (OS) and toxicity after low-dose rate I(125) permanent
      implant prostate brachytherapy (LDR-BRT) in elderly patients affected by prostate
      cancer. METHODS AND MATERIALS: Patients aged >=65 years with a diagnosis of
      prostate cancer and treated at our institution were retrospectively evaluated.
      All patients received LDR-BRT as monotherapy; the prescribed dose was 145 Gy to
      the prostate. Patients were stratified according to the National Comprehensive
      Cancer Network (NCCN) recurrence risk groups. Biochemical failure was defined
      according to the American Society of Therapeutic Radiology and Oncology (ASTRO)
      criteria. The Radiation Therapy Oncology Group (RTOG) scale was used for
      toxicity. The bDFS was calculated from implant date to biochemical recurrence.
      RESULTS: Between June 2003 and December 2008, 80 elderly patients with a median
      age of 75 (range, 65-86) years were treated with LDR-BRT: 51 low risk (64%), and
      29 intermediate risk (36%). Over a median follow-up period of 53 (range, 28-94)
      months, the global actuarial 5-year bDFS rate was 91.3% and the 5-year OS was
      95%. Toxicity was mild: late grade-3 genitourinary toxicity was observed in only
      four patients (5%). CONCLUSIONS: Our data suggest that LDR-BRT is effective and
      safe as monotherapy in elderly patients.

PMID- 22986693
TI  - Accuracy of visual analysis vs. apparent diffusion coefficient quantification in
      differentiating solid benign and malignant focal liver lesions with diffusion
      weighted imaging.
AB  - PURPOSE: The authors compared the accuracy of diffusion-weighted imaging (DWI)
      visual analysis (VA) vs. apparent diffusion coefficient quantification (ADC-Q) in
      assessing malignancy of solid focal liver lesions (FLLs). MATERIALS AND METHODS:
      Using a 1.5-T system, two radiologists retrospectively assessed as benign or
      malignant 50 solid FLLs: (a) by VA of signal intensity on DWI images at b=800
      s/mm(2) and ADC map; (b) by quantifying lesion ADC. Reference standard included
      histology or follow-up confirmation of diagnosis by a consensus panel. Receiver
      operating characteristic (ROC) curve analysis was performed. RESULTS: because of
      20 false-negative hepatocellular carcinomas, VA showed lower accuracy than ADC-Q
      (52.0% VS. 68.0%). however, stratified accuracy for metastases was higher with VA
      (75.0 VS. 66%). ADC and signal features of malignant and benign FLLs were found
      to largely overlap. CONCLUSIONS: VA performed worse than ADC-Q for hepatocellular
      carcinoma and better for metastases. Overall, the accuracy of both methods was
      limited because of the overlap in visual appearance and ADC values between solid
      benign and malignant FLLs.

PMID- 22986694
TI  - Acoustic radiation force impulse (ARFI) imaging with Virtual Touch Tissue
      Quantification in liver disease associated with cystic fibrosis in children.
AB  - PURPOSE: Cystic-fibrosis-associated liver disease (CFLD) may lead to portal
      hypertension (PHT) and cirrhosis. Clinical signs and biochemistry of liver
      involvement are not discriminating. The aim of the study was to evaluate the
      performance of acoustic radiation force impulse (ARFI) with virtual tissue
      quantification in comparison with clinical signs, biochemistry and standard
      hepatic ultrasound (US) patterns. MATERIALS AND METHODS: Virtual Touch Tissue
      Quantification, an implementation of US ARFI with shear-wave velocity (SWV)
      measurements was used in 75 children with cystic fibrosis (CF) and suspected CFLD
      to quantify hepatic stiffness. In each patient, ten measurements of SWV were
      performed on the right hepatic lobe. Patients were also evaluated by standard
      diagnostic tools (standard US, liver- and lung function tests,
      oesophagogastroscopy). RESULTS: Among CF patients, median SWV was significantly
      higher in patients with clinical, biochemical and US signs of hepatic involvement
      than in patients without US evidence of liver disease 1.08 m/s [(95% confidence
      interval (CI), 1.02-1.14]. Median SWV values in patients with portal
      hypertension, splenomegaly and oesophageal varices were 1.30 (95% CI, 1.17-1.43),
      1.54 (95% CI, 1.32-1.75) and 1.63 (95% CI, 1.26-1.99), respectively. Differences
      were significant (p<0.001). CONCLUSIONS: ARFI is an innovative screening
      technique able to help identify CFLD in children.

PMID- 22986695
TI  - Multimodality imaging of intraosseous ganglia of the wrist and their differential
      diagnosis.
AB  - Intraosseous ganglion (IOG) is the most frequently occurring bone lesion within
      the carpus and is often an incidental finding on radiographs obtained for other
      reasons. Two types of IOG have been described: an "idiopathic" form (or type I),
      the pathogenesis of which has not been completely clarified, and a "penetrating"
      form (or type II), caused by the intrusion of juxtacortical material (often a
      ganglion cyst of the dorsal soft tissue) into the cancellous bone compartment.
      The differential diagnosis for IOG is wide-ranging and complex, including lesions
      of posttraumatic (posttraumatic cystlike defects), degenerative (subchondral
      degenerative cysts), inflammatory [cystic rheumatoid arthritis, chronic
      tophaceous gout (CTG)], neoplastic (benign primary bone tumours and synovial
      proliferative lesions), ischaemic (Kienbock's disease or avascular osteonecrosis
      of the lunate) and metabolic (amyloidosis) origin. Multimodality imaging of IOGs
      is a useful diagnostic tool that provides complete morphological characterisation
      and differentiation from other intraosseous cystic abnormalities of the carpus.
      Thin-slice multidetector computed tomography (MDCT) can provide high-spatial
      resolution images of the cortical and cancellous bone compartments, allowing
      detection of morphological findings helpful in characterising bone lesions,
      whereas magnetic resonance (MR) imaging can simultaneously visualise bone,
      articular surfaces, hyaline cartilage, fibrocartilage, capsules and ligaments,
      along with intra- and periarticular soft tissues.

PMID- 22986696
TI  - Dynamic contrast-enhanced MR evaluation of prostate cancer before and after
      endorectal high-intensity focused ultrasound.
AB  - PURPOSE: The authors sought to determine the diagnostic performance of dynamic
      contrast-enhanced magnetic resonance (DCE-MR) imaging in the evaluation of
      prostate cancer before and after transrectal high-intensity focused ultrasound
      (HIFU) treatment. MATERIALS AND METHODS: We analysed 25 patients with prostate
      cancer. The prostate-specific antigen (PSA) value was evaluated 1, 4 and 6 months
      after treatment. DCE-MR imaging was performed the day prior to and 1, 4 and 6
      months after HIFU treatment. Transrectal prostate biopsies were obtained at the
      time of diagnosis and 6 months after treatment. RESULTS: Before treatment,
      intraglandular lesions were considered to be potential sites of neoplasm and
      subsequently confirmed as sites of prostate adenocarcinoma in all 25 patients
      based on prostatespecific antigen (PSA) values and histological examinations
      (rho=1; p<0.001). Using histology as the gold standard, DCE-MR imaging displayed
      100% sensitivity, 100% specificity, 100% positive predictive value and 100%
      negative predictive value before treatment. After HIFU treatment, DCE-MR imaging
      showed 100% sensitivity and 96% specificity. CONCLUSIONS: DCE-MR imaging can be
      used to visualise prostate adenocarcinoma. Several morphological and
      postgadolinium modifications in the follow-up DCE-MR images after HIFU treatment
      were also observed.

PMID- 22986697
TI  - Diffuse neoplasms of the pleural serosa.
AB  - This study describes the diffuse neoplastic conditions that may affect pleural
      membranes. These include mesothelioma, the most important and common malignancy
      of pleural origin, and metastatic involvement by carcinomas, lymphomas and
      thymomas. On the basis of diagnostic imaging, we identify the distinctive
      features of pleural involvement by each of these conditions and provide elements
      enabling accurate differential diagnosis. Finally, we discuss the best diagnostic
      approach in the case of suspected primary or secondary neoplastic involvement of
      pleural membranes.

PMID- 22986698
TI  - Malpractice claims in interventional radiology: frequency, characteristics and
      protective measures.
AB  - PURPOSE: The use of interventional radiology procedures has considerably
      increased in recent years, as has the number of related medicolegal litigations.
      This study aimed to highlight the problems underlying malpractice claims in
      interventional radiology and to assess the importance of the informed consent
      process. MATERIALS AND METHODS: The authors examined all insurance claims
      relating to presumed errors in interventional radiology filed by radiologists
      over a period of 14 years after isolating them from the insurance database of all
      radiologists registered with the Italian Society of Medical Radiology (SIRM)
      between 1 January1993 and 31 December 2006. RESULTS: In the period considered, 98
      malpractice claims were filed against radiologists who had performed
      interventional radiology procedures. In 21 cases (21.4%), the event had caused
      the patient's death. In >80% of cases, the event occurred in a public facility.
      The risk of a malpractice claim for a radiologist practising interventional
      procedures is 47 per 1,000, which corresponds to one malpractice claim for each
      231 years of activity. DISCUSSION: Interventional radiology, a discipline with a
      biological risk profile similar to that of surgery, exposes practitioners to a
      high risk of medicolegal litigation both because of problems intrinsic to the
      techniques used and because of the need to operate on severely ill patients with
      compromised clinical status. CONCLUSIONS: Litigation prevention largely depends
      on both reducing the rate of medical error and providing the patient with correct
      and coherent information. Adopting good radiological practices, scrupulous review
      of procedures and efficiency of the instruments used and audit of organisational
      and management processes are all factors that can help reduce the likelihood of
      error. Improving communication techniques while safeguarding the patient's right
      to autonomy also implies adopting clear and rigorous processes for obtaining the
      patient's informed consent to the medical procedure.

PMID- 22986699
TI  - Direct magnetic resonance (MR) shoulder arthrography: posterior approach under
      ultrasonographic guidance and abduction (PAUGA).
AB  - PURPOSE: This study was undertaken to assess the reliability of the posterior
      approach under ultrasonographic guidance (PAUGA), with the arm abducted, before
      performing direct magnetic resonance (MR) arthrography of the shoulder. MATERIALS
      AND METHODS: A total of 111 (82 men, 29 women; mean age, 24 years) underwent
      direct MR arthrography of the shoulder. Patients were enrolled because of
      glenohumeral instability (n=71), chronic shoulder pain (n=25), suspicion of
      rotator cuff tear (n=13) and adhesive capsulitis (n=2). Patients were placed in
      the lateral position, on the contralateral side to that being examined; the arm
      of the shoulder undergoing the examination was placed in slight internal rotation
      with the hand under the contralateral armpit. A gadolinium-based solution was
      injected into the articular capsule under cryoanaesthesia and sonographic
      guidance. A posterior approach was systematically applied. For each patient, the
      number of injection attempts, room time, complications and pain, as recorded on a
      10-point visual analogue scale (VAS), were noted. For quantitative parameters
      (room time and pain intensity), the mean and standard deviation (SD) were
      calculated. RESULTS: Direct MR arthrographies were performed successfully in all
      patients; no immediate or late major complications were observed. Fourteen
      patients (12.6%) reported temporary and self-limiting compromise of arm
      movements, and 13 patients (11.7%) reported a vagal reaction not requiring
      medication. In 102 cases (92%), the injection was successful at the first
      attempt, whereas in the remaining nine cases (8%), needle repositioning without
      any additional puncture was required to obtain clear sonographic depiction of the
      position of the needle tip. Mean room time was 7.2+/-1.4 min. Mean pain intensity
      was 3.2+/-0.4 on the 10-point VAS scale. CONCLUSIONS: PAUGA is a reliable and
      rapid technique that is well tolerated by patients and easy for the radiologist
      to perform.

PMID- 22986700
TI  - Role of whole-body 64-slice multidetector computed tomography in treatment
      planning for multiple myeloma.
AB  - PURPOSE: The authors evaluated the role of whole-body 64-slice multidetector
      computed tomography (WB-MDCT) in treatment planning for multiple myeloma.
      MATERIAL AND METHODS: This was a prospective study of 28 consecutive patients
      with multiple myeloma (19 men, nine women; age range, 51-73 years; mean age, 60
      years) who underwent WB-MDCT and conventional radiography (CR) of the skeleton.
      The images were interpreted for the presence of bony lesions, medullary lesions,
      fractures and extraosseous lesions. We evaluated any changes in treatment
      planning as a result of WB-MDCT findings. RESULTS: WB-MDCT was superior to CR for
      detecting bony lesions (p=0.001), especially of the spine (p=0.001) and thoracic
      cage (p=0.006). WB-MDCT upstaged 14 patients, with a significant difference in
      staging (p=0.002) between WB-MDCT and CR. Medullary involvement either focal
      (n=6) or diffuse (n=3) had a positive correlation with the overall score
      (r=0.790) and stage (r=0.618) of disease. Spine fractures were better detected at
      WB-MDCT (n=4) than at CR (n=2). Extraosseous soft tissue lesions (n=7) were
      detected only at WB-MDCT. Findings detected at the WB-MDCT led to changes in the
      patient's treatment plan in 39% of cases. Upstaging of seven patients (25%)
      altered the medical treatment plan, and four of 28 (14%) patients required
      additional radiotherapy (7%) and vertebroplasty (7%). CONCLUSIONS: We conclude
      that WB-MDCT has an impact on treatment planning and prognosis in patients with
      multiple myeloma, as it has high rate of detecting cortical and medullary bone
      lesions, spinal fracture and extraosseous lesions. This information may alter
      treatment planning in multiple myeloma due to disease upstaging and detection of
      spine fracture and extraosseous spinal lesions.

PMID- 22986702
TI  - Determination of proton- and oxide ion tracer diffusion in lanthanum tungstate
      (La/W = 5.6) by means of ToF-SIMS.
AB  - Tracer diffusion of protons and oxide ions, as well as chemical diffusion of
      water, have been determined for the high temperature proton conductor lanthanum
      tungstate by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS).
      The oxygen tracer diffusion and surface exchange coefficients, D(O)* and k(O)*,
      were measured after exchange anneals in water vapor enriched in H(2)(18)O between
      350 and 620  degrees C, and the apparent activation energies were 176 and 82 kJ
      mol(-1), respectively. The hydrogen tracer diffusion coefficient (D(H)*) was
      measured between 220 and 320  degrees C after exchange anneals in D(2)O
      containing atmospheres, and the apparent activation energy was 63 kJ mol(-1). The
      extracted D(H)* agrees with the results of transient conductivity- and TG
      measurements. Chemical diffusion and surface exchange coefficients, D(H)delta and
      k(H)delta, were measured at 250 and 400  degrees C, and the result confirms that
      the material is hydrated by ambipolar sluggish transport of protons and oxide
      ions. The surface exchange coefficients were compared to the result of TG
      relaxation, suggesting that access to oxygen vacancies limits the overall surface
      exchange reaction under incorporation of water and oxygen.

PMID- 22986701
TI  - Overview of non-invasive factors (low level laser and low intensity pulsed
      ultrasound) accelerating tooth movement during orthodontic treatment.
AB  - The need for orthodontic treatment is increasing all the time. As the treatment
      is time consuming ranging from a year to several years, any method of reducing
      the period of treatment and increasing the quality of the tissue will be
      beneficial to patients. The use of non-invasive techniques such as low level
      laser therapy and low intensity pulsed ultasound in accelerating orthodontic
      tooth movement are promising. Thus, this overview study will help to generate
      more understanding about the background information and the possible applications
      of them in daily orthodontics, depending on previous literature searching for
      reviews and original research articles. 

PMID- 22986703
TI  - Respiratory distress syndrome at birth is a risk factor for hospitalization for
      lower respiratory tract infections in infancy.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) and hospitalization for lower
      respiratory tract infection (LRTI; specifically, respiratory syncytial virus) are
      important causes of morbidity in infancy. Whether RDS at birth is an independent
      risk factor for LRTI is unknown. This study estimated the risk of LRTI-related
      hospitalization among late preterm infants with a history of RDS. METHODS: The
      population-based cohort from Quebec included all late preterm infants (32-36
      weeks gestational age) born in 1996 to 1997. RDS was identified by International
      Classification of Diseases, Ninth Revision code 769, and a comparison cohort
      generated from all without RDS. A multivariable model estimated the adjusted odds
      ratio of LRTI-related hospitalization among late preterm infants with a history
      of RDS; and the incidence and increased risk of childhood chronic respiratory
      morbidity was calculated. RESULTS: Of the 7488 late preterms, 459 (6.1%) had a
      history of RDS; 525 late preterms (7.0%) were hospitalized for LRTI in infancy,
      including 57 (12.4%) with RDS. The adjusted odds ratio for LRTI-related
      hospitalization associated with RDS was 1.6 (1.2-2.2). Other significant risk
      factors included male sex, or diagnosis of other respiratory conditions,
      diaphragm anomalies, bacteremia, intraventricular hemorrhage, congenital heart
      disease or respiratory system anomalies. Late preterm infants with a history of
      RDS were also at a significantly increased risk of childhood chronic respiratory
      morbidity. CONCLUSIONS: Late preterms with a history of RDS are at a 60%
      increased risk of LRTI-related hospitalization in infancy compared with late
      preterm infants without RDS. Such infants may benefit from interventions
      decreasing the risk of contracting respiratory viruses causing acute LRTI.

PMID- 22986704
TI  - Prevalence of human leukocyte antigen-B*5701 among HIV-infected children in
      Thailand and Cambodia: implications for abacavir use.
AB  - Human leukocyte antigen (HLA)-B*5701 allele is associated with abacavir
      hypersensitivity. Limited data among Asians showed lower rates of HLA-B*5701
      compared with Caucasians. In 296 children with HIV in Thailand and Cambodia, the
      prevalence of HLA-B*5701 was 4.0% (95% confidence interval: 1.6-8.0%) among Thai
      and 3.4% (95% confidence interval: 0.9-8.5%) among Cambodian children. HLA-B*5701
      carriage is not uncommon among Thai and Cambodian children; it is close to the
      prevalence found in European and higher than the prevalence found in East Asian
      and African studies.

PMID- 22986705
TI  - Influenza A/H1N1 vaccination response is inadequate in down syndrome children
      when the latest cut-off values are used.
AB  - We determined the response of 48 Down syndrome children to 2 doses of influenza
      A/H1N1 vaccination. Ninety-two percent of the children reached the previously
      defined protective level (hemagglutination-inhibition titer >=1:40), but only 27%
      of the children reached the level of >=1:110 which was recently described to
      predict the conventional 50% clinical protection rate in children. Further
      studies, and potentially adaptations of the schedule, are needed.

PMID- 22986706
TI  - Profiling of ileal carcinoids.
AB  - Identification of common molecular mechanisms is needed to facilitate the
      development of new treatment options for patients with ileal carcinoids. PURPOSE
      OF REVIEW: Recent profiling studies on ileal carcinoids were examined to obtain a
      comprehensive view of risk factors, genetic aberrations, and transcriptional
      alterations. Special attention was paid to mechanisms that could provide novel
      targets for therapy. RESULTS: Genome-wide association studies have shown that
      single nucleotide polymorphisms (SNPs) at IL12A and DAD1 are associated with an
      increased risk of ileal carcinoids. Genomic profiling revealed distinct patterns
      of copy-number alterations in ileal carcinoids. Two groups of carcinoids could be
      identified by hierarchical clustering. A major group of tumors was characterized
      by loss on chromosome 18 followed by additional losses on chromosomes 3p, 11q,
      and 13. Three minimal common regions of deletions were identified at 18q21.1
      q21.31, 18q22.1-q22.2, and 18q22.3-q23. A minor group of tumors was characterized
      by clustered gains on chromosomes 4, 5, 7, 14, and 20. Expression profiling
      identified three groups of ileal carcinoids by principal component analysis.
      Tumor progression was associated with changes in gene expression including
      downregulation of MIR133A. Candidate genes for targeted therapy included
      ERBB2/HER2, DAD1, PRKCA, RYBP, CASP1, CASP4, CASP5, VMAT1, RET, APLP1, OR51E1,
      GPR112, SPOCK1, RUNX1, and MIR133A. CONCLUSION: Profiling of ileal carcinoids has
      revealed recurrent genetic alterations and distinct patterns of gene expression.
      Frequent alterations in cellular pathways and genes were identified, suggesting
      novel targets for therapy. Translational studies are needed to validate suggested
      molecular targets.

PMID- 22986707
TI  - Transcriptomic and epigenetic changes in the hypothalamus are involved in an
      increased susceptibility to a high-fat-sucrose diet in prenatally stressed female
      rats.
AB  - Disturbances in the prenatal period are linked to metabolic disorders in
      adulthood, implying the hypothalamic systems of appetite and energy balance
      regulation. In order to analyze the central effects of a high-fat-sucrose (HFS)
      diet in prenatally stressed (PNS) female adult rats, Wistar dams were exposed to
      chronic-mild-stress during the third week of gestation and were then compared
      with unstressed controls. Adult female offspring were fed a chow or HFS diet for
      10 weeks. Changes in body weight, adiposity as well as expression and methylation
      levels of selected hypothalamic genes were analyzed. PNS induced lower
      birthweight and body length with no changes in body fat mass. After the HFS diet,
      the expected overweight model was observed accompanied by higher adiposity and
      insulin resistance, which was worsened by PNS. The stress model induced higher
      energy intake in adulthood. Hypothalamic gene expression analysis revealed that
      the HFS diet decreased Slc6a3 (dopamine active transporter), NPY (neuropeptide Y)
      and IR (insulin receptor) and increased POMC (pro-opiomelanocortin). Hypothalamic
      DNA methylation levels in the promoter region of Slc6a3 revealed that Slc6a3 was
      hypermethylated by the HFS diet in CpG site -53 bp to the transcription start
      site. HFS diet also hypermethylated CpG site -167 bp of the POMC promoter only in
      nonstressed animals. No correlations were found between gene expression and DNA
      methylation levels. These results imply that early-life stress in females
      increased predisposition to diet-induced obesity in adulthood.

PMID- 22986708
TI  - Abstracts of European Vitreoretinal Update 2012. September 6-9, 2012.

PMID- 22986713
TI  - Cervical slide tracheoplasty.
AB  - OBJECTIVE: To describe our experience with cervical slide tracheoplasty (CST) in
      managing complex laryngotracheal disorders. DESIGN: Retrospective analysis.
      SETTING: Quaternary care pediatric institution. PATIENTS: The study included 29
      patients who underwent CST without cardiopulmonary bypass at our institution from
      January 2003 to January 2011. MAIN OUTCOME MEASURE: Surgery-specific and overall
      operative success. RESULTS: The most common airway lesion in our cohort of 29
      patients (mean age, 10.7 years) was tracheal stenosis (n = 18); 10 of 18 patients
      had long-segment acquired tracheal stenosis. Operation-specific success was
      achieved in 23 of 29 patients (79%), including all 10 patients with long-segment
      acquired tracheal stenosis. Six patients failed initial CST and required
      additional surgical procedures. Overall success was achieved in 3 of these
      patients. Patients with subglottic stenosis (n = 7), concomitant glottic stenosis
      (n = 4), and multilevel airway lesions (n = 10) had lower operation-specific and
      overall operative success than did patients with other airway lesions. Four
      patients (14%) experienced complications. CONCLUSIONS: Cervical slide
      tracheoplasty is a valuable technique that should be added to the surgical
      armamentarium for patients requiring open airway reconstruction. This technique
      yields a high success rate in treating patients with a broad spectrum of complex
      laryngotracheal disorders.

PMID- 22986710
TI  - Rapid stimulating effect of the antiarrhythmic agent amiodarone on absorption of
      organic anion compounds.
AB  - In a clinical setting, changes in pharmacokinetics due to drug-drug interactions
      can often directly affect the therapeutic safety and efficacy of drugs. Recently,
      interest has been shown in drug-drug interactions in the intestine. It is now
      recognized that changes in the functions of drug transporters substantially
      influence the absorption of administered drugs from the intestine. Amiodarone
      (AMD) is a potent drug used in the treatment of serious supraventricular and
      ventricular tachyarrhythmias. Despite its potent pharmacological effects, its
      wide clinical use is precluded by drug-drug interactions. In this study, we
      characterized the transporter function between AMD and various compounds in human
      intestinal model Caco-2 cells. AMD significantly and rapidly increased the uptake
      of [(3)H]estrone-3-sulfate (E-3-S) for 5 min. The apical-to-basal transport of
      [(3)H]E-3-S was significantly increased by AMD. The AMD-stimulated [(3)H]E-3-S
      uptake was inhibited by organic anion transporting polypeptide (OATP) substrates.
      Caco-2 cells treated with AMD showed increased OATP2B1 expression on the cell
      surface. AMD also increased the absorption of sulfobromophthalein (BSP), which is
      a typical organic anion compound, and the expression level of Oatp2b1 at the
      membrane in in vivo experiments. The results indicate that AMD induces
      OATP2B1/Oatp2b1 expression at the membrane in the intestine and enhances
      absorption of organic anion compounds.

PMID- 22986714
TI  - Changing trends in smoking and alcohol consumption in patients with oral cancer
      treated at Memorial Sloan-Kettering Cancer Center from 1985 to 2009.
AB  - OBJECTIVE: To describe smoking and alcohol consumption trends in patients with
      oral cavity cancer over the past 25 years. DESIGN: Retrospective cohort study.
      SETTING: Single-institution tertiary care cancer center. PATIENTS: Patients with
      oral cancer treated primarily with surgery from 1985 to 2009. Patients with
      previous head and neck cancer were excluded. MAIN OUTCOME MEASURES: The medical
      records of 1617 patients were reviewed. Patient demographics and details on
      smoking and alcohol consumption were recorded. Patients were divided in 5
      different cohorts according to the year of initial surgery. RESULTS: There were
      no differences in sex, age, or stage of disease among cohorts. Oral tongue was
      the most common subsite (49%). There was a progressive decrease in tobacco use;
      80% in cohort 1 vs 60% in cohort 5 (P < .001). A decrease in the daily amount of
      tobacco used was also found; 55% of patients in cohort 1 smoked more than 1 pack
      per day compared with 30% in cohort 5 (P < .001). Alcohol consumption decreased
      from 80% in cohort 1 to 67% in cohort 5 (P < .007). The percentage of patients
      who consumed more than 3 drinks per day decreased from 23% in cohort 1 to 9% in
      cohort 5 (P < .001). CONCLUSION: Over the past 25 years there has been a
      progressive decrease in the prevalence of tobacco and alcohol users in patients
      with oral cancer.

PMID- 22986716
TI  - The effectiveness of 1-point fixation for zygomaticomaxillary complex fractures.
AB  - OBJECTIVES: To introduce the surgical technique of 1-point fixation at the
      zygomaticomaxillary buttress (ZMB) and to verify its effectiveness using 3
      dimensional computed tomography (3D CT). DESIGN: Case series with chart review.
      SETTING: Academic tertiary care medical center. PATIENTS AND METHODS: The study
      included 29 patients who underwent 1-point fixation at the ZMB for
      zygomaticomaxillary complex fractures without comminution of lateral orbital rim
      fractures. Preoperative and postoperative 3D CT scans were obtained to evaluate
      vertical and horizontal changes of the zygoma, which were were analyzed according
      to preoperative 3D CT findings. RESULTS: The ZMB area was fixed with a resorbable
      system in 26 patients and with a metal system in 3 patients. After surgery, the
      mean vertical change improved from 1.28 degrees  to 0.58 degrees  (P < .001), and
      the mean horizontal change improved from 1.71 degrees  to 0.92 degrees  (P <
      .001). Postoperative vertical movement of the zygoma was not significantly
      affected by comminution of the inferior orbital wall, zygomaticofrontal process
      displacement, or comminution of the ZMB area and zygomatic arch (P > .05 for
      each). However, comminution of the ZMB area had an adverse effect on horizontal
      movement of the zygoma (P = .03). Complications after surgery included facial
      cellulitis associated with acute sinusitis in 1 patient, who was treated
      successfully. No patient required revision reduction because of facial deformity.
      CONCLUSION: Our findings suggest that 1-point fixation at the ZMB provides
      sufficient stability of the zygomaticomaxillary complex without comminuted
      fractures of the lateral orbital rim.

PMID- 22986715
TI  - Ultrasonography in the treatment of a pediatric midline neck mass.
AB  - OBJECTIVE: To assess the effectiveness of ultrasonography for determining which
      pediatric midline neck masses should be treated surgically. DESIGN: Retrospective
      study. SETTING: Tertiary care pediatric hospital. PATIENTS: Pediatric patients
      with a midline neck mass who underwent ultrasonography from 2003 to 2011. MAIN
      OUTCOME MEASURES: Demographics, ultrasonography, and surgical and pathology
      reports were studied. The ultrasonography findings and pathological analyses were
      compared. RESULTS: One hundred twenty-two patients met the inclusion criteria.
      The most common diagnosis obtained by ultrasonography was thyroglossal duct cyst
      (48.4%), followed by reactive lymph node (27.9%). Ninety-five of 122 patients
      (77.9%) underwent surgery. Twenty-seven patients (22.1%) were treated
      nonsurgically. The diagnosis and characteristics obtained from ultrasonography
      were confirmed by surgical pathologic analysis in 84.2% of the surgical cases. Of
      the 95 patients who underwent surgery, 85 (89.5%) had a non-lymph node lesion
      diagnosed by ultrasonography and confirmed by pathologic analysis.
      Ultrasonography was only 66.1% accurate in specifically diagnosing thyroglossal
      duct cyst and 30.0% accurate in specifically diagnosing reactive lymph node when
      compared with surgical specimens. CONCLUSIONS: Ultrasonography is helpful in
      determining the pediatric midline neck masses that need to be removed surgically.
      It is less helpful in determining the exact pathologic characteristics of the
      lesion.

PMID- 22986718
TI  - Factors associated with quality of life after ear surgery in patients with
      chronic otitis media.
AB  - OBJECTIVE: To assess the factors affecting health-related quality of life (HRQOL)
      after ear surgery in patients with chronic otitis media (COM). DESIGN:
      Prospective questionnaire-based outcome study. SETTING: Tertiary care
      institution. PATIENTS: The study population comprised 205 patients aged 21 to 67
      years referred for ear surgery owing to COM with or without cholesteatoma between
      November 2009 and March 2011. INTERVENTIONS: The ear surgery for COM included
      tympanoplasty, with or without mastoidectomy. The Korean version of the Chronic
      Ear Survey (K-CES), a disease-specific outcome survey, was administered before
      and 12 months after surgery. MAIN OUTCOME MEASURES: The primary outcome measures
      were the total score and subscale score, including an activity restriction-based
      subscale, symptom subscale, and medical resource utilization subscale. The scores
      were analyzed with disease- and patient-related factors affecting health-related
      quality of life. RESULTS: Of the 205 patients enrolled, complete data from 156
      patients were available for this study. The K-CES score in patients with COM
      improved after ear surgery in total and in all subscales of the K-CES (P < .001).
      In univariable analysis, poor improvement in total K-CES score was more likely to
      occur after ear surgery in patients with postoperative complications, diabetes
      mellitus, hearing loss as a chief complaint, lower air conduction threshold in
      postoperative audiometry, and a high level of education and in those who
      underwent canal wall down mastoidectomy (P < .05). Multivariable analysis using
      multiple linear regression revealed that the occurrence of complications,
      presence of diabetes mellitus, level of education, and postoperative air
      conduction thresholds were independent factors for poor improvement in total K
      CES score (P < .05). CONCLUSION: Recognition of factors that have significant
      relation with subjective outcomes may help surgeons to identify patients who are
      prone to have a lower satisfaction and provide useful information in preoperative
      counseling.

PMID- 22986709
TI  - Polymorphic transporters and platinum pharmacodynamics.
AB  - Several solute carriers and ATP-binding cassette transporters have been
      implicated in the influx or efflux of platinum-based chemotherapeutic agents such
      as cisplatin, carboplatin, and oxaliplatin. Given that many of these proteins are
      highly polymorphic, the genetic status of these proteins could be an important
      contributor to the extensive interindividual pharmacokinetic variability
      associated with the clinical use of these agents. In this review article, we
      provide an updated overview of the various transporters that have shown promise
      in animal models or patient populations in facilitating the movement of platinum
      based agents across cell membranes, and how their function is associated with
      drug disposition or pharmacodynamic effects.

PMID- 22986719
TI  - Categorizing nasal polyps by severity and controller therapy.
AB  - OBJECTIVE: To analyze a new categorization of chronic rhinosinusitis with nasal
      polyposis (CRSwNP) according to severity and controller therapy, modified from
      the 2007 stepwise treatment for asthma. DESIGN: Prospective categorization of 50
      new or established patients over a 3-month period. SETTING: Tertiary center of
      Hotel-Dieu de France Hospital, Beirut, Lebanon. PATIENTS: Fifty consecutive adult
      patients with nasal polyposis referred by primary care physicians for sinonasal
      complaints or by pulmonologists for worsening lower airway control including
      asthma. INTERVENTIONS: All patients were categorized according to CRSwNP severity
      scale and treated with stepwise therapy based on the study schematic. MAIN
      OUTCOME MEASURES: The Modified Sinonasal Questionnaire and the visual analog
      scale were used to assess patients' response to the treatment regimen and to
      modify the severity scale and the step treatment accordingly. RESULTS: Ten new
      medication-naive patients with CRSwNP were categorized by severity, which
      directed the subsequent treatment plan. All patients showed improvement in
      severity with the stepwise treatment plan. Thirty-seven of 40 patients with
      established CRSwNP seen in follow-up were easily categorized by degree of
      control, and subsequent treatment directed by therapy guidelines resulted in
      improvement. CONCLUSIONS: Initial categorization of medication-naive patients
      with CRSwNP and patients with established CRSwNP facilitated delivery of
      successful directed stepwise therapy that resulted in improvement of
      classification of severity in most patients. This proposed classification may
      provide a useful template for future studies comparing patients with CRSwNP.

PMID- 22986721
TI  - Desmoplastic fibroma arising from the anterior maxillary sinus in a child.

PMID- 22986720
TI  - Innate immunity mediating inflammation secondary to endotracheal intubation.
AB  - OBJECTIVE: To investigate the inflammatory markers associated with short-term
      endotracheal intubation in healthy surgical patients. DESIGN: An observational
      and prospective study of subjects scheduled for same-day surgery procedures.
      SETTING: Level I trauma center. PATIENTS: Fourteen healthy patients intubated for
      same-day surgery procedures. The median duration of surgery was 3 hours.
      INTERVENTIONS: Serial lavages above the tracheal cuff were obtained at the
      beginning of surgery, at 1 hour, and at the end of surgery; samples were assayed
      for cellular counts and levels of cytokines and complement 5a (C5a). RESULTS: The
      total number of polymorphonuclear cells (PMNs) increased almost 10-fold from
      intubation to extubation (P < .01). The levels of 3 of the cytokines measured in
      tracheal lavage supernatants were significantly elevated over the time of
      intubation: tumor necrosis factor (TNF) (P < .01), interleukin 6 (IL-6) (P <
      .01), and IL-1beta (P < .025). Levels of IL-8 showed an upward trend over time
      but were not significantly increased; C5a levels were significantly elevated over
      time (P < .05). CONCLUSIONS: Short-term intubation in healthy patients resulted
      in significant tracheal inflammation. Involvement of the innate immune system as
      documented in the present study provides information that may help to better
      understand the pathophysiologic characteristics of subglottic stenosis and other
      endotracheal injuries secondary to endotracheal intubation.

PMID- 22986722
TI  - IgG4-sclerosing pseudotumor of the trachea: a case report and review of the
      literature.

PMID- 22986723
TI  - Radiology quiz case 1. Riedel thyroiditis.

PMID- 22986725
TI  - Radiology quiz case 2. Docetaxel (Taxotere)-induced photosensitivity.

PMID- 22986727
TI  - Pathology quiz case 1. Ceruminous gland adenocarcinoma.

PMID- 22986729
TI  - Pathology quiz case 2. Tophaceous pseudogout (calcium pyrophosphate deposition
      disease [CPDD]) of the TMJ.

PMID- 22986731
TI  - Fasting plasma glucose and HbA1c in cardiovascular risk prediction: a sex
      specific comparison in individuals without diabetes mellitus.
AB  - AIMS/HYPOTHESIS: This study aimed to assess the cardiovascular risk of
      individuals with fasting plasma glucose (FPG)- and/or HbA(1c)-defined prediabetes
      (5.6-6.9 mmol/l and 39-47 mmol/mol [5.7-6.4%], respectively) or manifest diabetes
      mellitus and to evaluate whether FPG or HbA(1c) can improve risk prediction
      beyond that estimated by the Systematic Coronary Risk Evaluation (SCORE) chart in
      individuals without diabetes mellitus. METHODS: Cox regression was employed to
      estimate HRs for primary incident cardiovascular events (CVEs) in a cohort of
      8,365 individuals aged 50-74 years. Furthermore, HbA(1c) and FPG were added
      individually to the variables of the SCORE and measures of model discrimination
      and reclassification were assessed. RESULTS: During 8 years of follow-up, 702
      individuals had a primary CVE. After adjusting for conventional cardiovascular
      risk factors, HRs were attenuated close to one for the prediabetes groups
      (especially for women), whereas a 1.7- and a 1.9-fold increased risk persisted
      for men and women with diabetes, respectively. Extension of the SCORE variables
      by either FPG or HbA(1c) did not improve its predictive abilities in individuals
      without diabetes. There was a non-significant net reclassification improvement
      for men when HbA(1c) was added (2.2%, p = 0.16). CONCLUSIONS/INTERPRETATION: The
      increased cardiovascular risk of individuals with FPG- or HbA(1c)-defined
      prediabetes can mainly be explained by other cardiovascular risk factors. Adding
      FPG or HbA(1c) did not significantly improve CVE risk prediction by the SCORE
      variables in individuals without diabetes mellitus.

PMID- 22986732
TI  - "Trivalent influenza vaccination of healthy adults 3 years after the onset of
      swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v
      constituent?".
AB  - Influenza vaccination is advised annually to reduce the burden of influenza
      disease. For sufficient vaccine campaigns also a continuous adoption of influenza
      vaccines are necessary, due to particularly high genetic variability of influenza
      A virus. Therefore, we evaluate the effectiveness of the trivalent influenza
      vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune
      response was investigated in paired sera from 92 healthcare workers with the
      hemagglutination inhibition assay (HI). Protective antibody levels (HI titer
      >=40) were found after vaccination for influenza A/California/07/2009(H1N1):
      84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47]
      and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the
      currently circulating virus strains. However, the highest seroprevalence rate was
      found against influenza B; pre- and post-vaccination titers as well, which may be
      due to comparatively high virus preservation. Remarkable, lowest seropositivity
      was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd
      immunity was still not achieved. It can be assumed that a high influenza A herd
      immunity may be a requirement for a successful booster vaccination.

PMID- 22986733
TI  - Cobalt complexes bearing scorpionate ligands: synthesis, characterization,
      cytotoxicity and DNA cleavage.
AB  - A number of novel, water-stable redox-active cobalt complexes of the C
      functionalized tripodal ligands tris(pyrazolyl)methane XC(pz)(3) (X = HOCH(2),
      CH(2)OCH(2)Py or CH(2)OSO(2)Me) are reported along with their effects on DNA. The
      compounds were isolated as air-stable solids and fully characterized by IR and
      FIR spectroscopies, ESI-MS(+/-), cyclic voltammetry, controlled potential
      electrolysis, elemental analysis and, in a number of cases, also by single
      crystal X-ray diffraction. They showed moderate cytotoxicity in vitro towards
      HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma human cancer cell
      lines. This viability loss is correlated with an increase of tumour cell lines
      apoptosis. Reactivity studies with biomolecules, such as reducing agents,
      H(2)O(2), plasmid DNA and UV-visible titrations were also performed to provide
      tentative insights into the mode of action of the complexes. Incubation of Co(II)
      complexes with pDNA induced double strand breaks, without requiring the presence
      of any activator. This pDNA cleavage appears to be mediated by O-centred radical
      species.

PMID- 22986735
TI  - Development of amperometric lysine biosensors based on Au
      nanoparticles/multiwalled carbon nanotubes/polymers modified Au electrodes.
AB  - The construction of two amperometric l-lysine biosensors is described in this
      study. The construction comprises the covalent immobilization of lysine oxidase
      (LOx) onto nanocomposite composed of gold nanoparticles (AuNPs) and carboxylated
      multiwalled carbon nanotubes (c-MWCNT), decorated on (i) polyaniline (PANI) and
      (ii) poly 1,2 diaminobenzene (DAB), electrodeposited on Au electrodes. The
      biosensors were characterized by scanning electron microscopy (SEM), Fourier
      transform infrared (FTIR) and electrochemical impedance spectroscopy (EIS)
      studies. The optimum response (current) was observed within 2 s at pH 7.0 and 25 
      degrees C for LOx/AuNPs/c-MWCNT/PANI/Au, and 4 s at pH 7.0 and 30  degrees C for
      LOx/AuNPs/c-MWCNT/DAB/Au electrodes. There was a linear relationship between
      current and lysine concentration ranging from 5.0 to 600 MUM for LOx/AuNPs/c
      MWCNT/PANI/Au with a detection limit of 5.0 MUM, and 20 to 600 MUM for the
      LOx/AuNPs/c-MWCNT/DAB/Au electrode with a detection limit of 20 MUM. The PANI
      modified electrode was in good agreement with the standard HPLC method, with a
      better correlation (r = 0.992) compared to the DAB modified electrode (r =
      0.986). These observations revealed that the PANI modified Au electrode was
      better than the DAB modified electrode, and hence it was employed for the
      determination of lysine in milk, pharmaceutical tablets and sera. The PANI
      modified electrode showed a half life of 120 days, compared to that of 90 days
      for the DAB modified electrode, after their 100 uses, when stored at 4  degrees
      C.

PMID- 22986734
TI  - Altered cellular membrane fluidity levels and lipid peroxidation during
      experimental pancreas transplantation.
AB  - Although the pathogenesis of ischemia reperfusion (IR) injury is based on complex
      mechanisms, free radicals play a central role. We evaluated membrane fluidity and
      lipid peroxidation during pancreas transplantation (PT) performed in 12 pigs (six
      donors and six recipients). Fluidity was measured by fluorescence spectroscopy,
      and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations were used
      as an index of lipid oxidation. Pancreatic tissues were collected as follows: (A)
      donor, immediately before vascular clamping; (B) graft, following perfusion
      lavage with University of Wisconsin preservation fluid; (C) graft, after 16 h of
      cold ischemia; and (D) recipient, 30 min vascular postreperfusion. Fluidity and
      MDA and 4-HDA concentrations were similar in cases A, B, and C. However, there
      was significant membrane rigidity and increased lipid peroxidation after
      reperfusion (D). These findings suggest that reperfusion exaggerates oxidative
      damage and may account for the rigidity in the membranes of allografts during PT.

PMID- 22986736
TI  - More about imatinib and nilotinib combination therapy in chronic myeloid
      leukemia.

PMID- 22986737
TI  - The FGFR4-G388R single-nucleotide polymorphism alters pancreatic neuroendocrine
      tumor progression and response to mTOR inhibition therapy.
AB  - Pancreatic neuroendocrine tumors (pNET), also known as islet cell tumors, exhibit
      a wide range of biologic behaviors ranging from long dormancy to rapid
      progression. Currently, there are few molecular biomarkers that can be used to
      predict recurrence/metastasis or response to therapy. This study examined the
      predictive and prognostic value of a single nucleotide polymorphism substituting
      an arginine (R) for glycine (G) in codon 388 of the FGFR4 transmembrane domain.
      We established the FGFR4 genotype of 71 patients with pNETs and correlated
      genotype with biologic behavior. We created an in vivo model of pNET with BON1
      cells and transfected them with either FGFR4-G388 or FGFR4-R388 to determine the
      mechanism of action and to examine response to the mTOR inhibitor everolimus. We
      then validated the predictive results of experimental studies in a group of
      patients treated with everolimus. FGFR4-R388 is associated with more aggressive
      clinical behavior in patients with pNETs with a statistically significant higher
      risk of advanced tumor stage and liver metastasis. Using an orthotopic mouse
      xenograft model, we show that FGFR4-R388 promotes tumor progression by increasing
      intraperitoneal spread and metastatic growth within the liver. Unlike FGFR4-G388,
      FGFR4-R388 BON1 tumors exhibited diminished responsiveness to everolimus.
      Concordantly, there was a statistically significant reduction in response to
      everolimus in patients with FGFR4-R388. Our findings highlight the importance of
      the FGFR4 allele in pNET progression and identify a predictive marker of
      potential therapeutic importance in this disease.

PMID- 22986738
TI  - Neuropilin-1-dependent regulation of EGF-receptor signaling.
AB  - Neuropilin-1 (NRP1) is a coreceptor for multiple extracellular ligands. NRP1 is
      widely expressed in cancer cells and in advanced human tumors; however, its
      functional relevance and signaling mechanisms are unclear. Here, we show that
      NRP1 expression controls viability and proliferation of different cancer cells,
      independent of its short intracellular tail. We found that the extracellular
      domain of NRP1 interacts with the EGF receptor (EGFR) and promotes its signaling
      cascade elicited upon EGF or TGF-alpha stimulation. Upon NRP1 silencing, the
      ability of ligand-bound EGFR to cluster on the cell surface, internalize, and
      activate the downstream AKT pathway is severely impaired. EGFR is frequently
      activated in human tumors due to overexpression, mutation, or sustained
      autocrine/paracrine stimulation. Here we show that NRP1-blocking antibodies and
      NRP1 silencing can counteract ligand-induced EGFR activation in cancer cells.
      Thus our findings unveil a novel molecular mechanism by which NRP1 can control
      EGFR signaling and tumor growth.

PMID- 22986739
TI  - NLRP3 suppresses NK cell-mediated responses to carcinogen-induced tumors and
      metastases.
AB  - The NLRP3 inflammasome acts as a danger signal sensor that triggers and
      coordinates the inflammatory response upon infectious insults or tissue injury
      and damage. However, the role of the NLRP3 inflammasome in natural killer (NK)
      cell-mediated control of tumor immunity is poorly understood. Here, we show in a
      model of chemical-induced carcinogenesis and a series of experimental and
      spontaneous metastases models that mice lacking NLRP3 display significantly
      reduced tumor burden than control wild-type (WT) mice. The suppression of
      spontaneous and experimental tumor metastases and methylcholanthrene (MCA)
      induced sarcomas in mice deficient for NLRP3 was NK cell and IFN-gamma-dependent.
      Focusing on the amenable B16F10 experimental lung metastases model, we determined
      that expression of NLRP3 in bone marrow-derived cells was necessary for optimal
      tumor metastasis. Tumor-driven expansion of CD11b(+)Gr-1(intermediate) (Gr
      1(int)) myeloid cells within the lung tumor microenvironment of NLRP3(-/-) mice
      was coincident with increased lung infiltrating activated NK cells and an
      enhanced antimetastatic response. The CD11b(+)Gr-1(int) myeloid cells displayed a
      unique cell surface phenotype and were characterized by their elevated production
      of CCL5 and CXCL9 chemokines. Adoptive transfer of this population into WT mice
      enhanced NK cell numbers in, and suppression of, B16F10 lung metastases.
      Together, these data suggested that NLRP3 is an important suppressor of NK cell
      mediated control of carcinogenesis and metastases and identify CD11b(+)Gr-1(int)
      myeloid cells that promote NK cell antimetastatic function.

PMID- 22986740
TI  - CD22 antigen is broadly expressed on lung cancer cells and is a target for
      antibody-based therapy.
AB  - Most patients with lung cancer still die from their disease, necessitating
      additional options to improve treatment. Here, we provide evidence for targeting
      CD22, a cell adhesion protein known to influence B-cell survival that we found is
      also widely expressed in lung cancer cells. In characterizing the antitumor
      activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed
      CD22 expression by multiple approaches in various lung cancer subtypes, including
      7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in
      vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and
      tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the
      development of pulmonary metastasis and extended overall survival. The finding
      that CD22 is expressed on lung cancer cells is significant in revealing a
      heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests
      that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a
      malignancy that has few tumor-specific targets.

PMID- 22986741
TI  - Metabolic associations of reduced proliferation and oxidative stress in advanced
      breast cancer.
AB  - Aberrant metabolism is a hallmark of cancer, but whole metabolomic flux
      measurements remain scarce. To bridge this gap, we developed a novel metabolic
      phenotypic analysis (MPA) method that infers metabolic phenotypes based on the
      integration of transcriptomics or proteomics data within a human genome-scale
      metabolic model. MPA was applied to conduct the first genome-scale study of
      breast cancer metabolism based on the gene expression of a large cohort of
      clinical samples. The modeling correctly predicted cell lines' growth rates,
      tumor lipid levels, and amino acid biomarkers, outperforming extant metabolic
      modeling methods. Experimental validation was obtained in vitro. The analysis
      revealed a subtype-independent "go or grow" dichotomy in breast cancer, where
      proliferation rates decrease as tumors evolve metastatic capability. MPA also
      identified a stoichiometric tradeoff that links the observed reduction in
      proliferation rates to the growing need to detoxify reactive oxygen species.
      Finally, a fundamental stoichiometric tradeoff between serine and glutamine
      metabolism was found, presenting a novel hallmark of estrogen receptor (ER)(+)
      versus ER(-) tumor metabolism. Together, our findings greatly extend insights
      into core metabolic aberrations and their impact in breast cancer.

PMID- 22986742
TI  - The V-ATPase-inhibitor archazolid abrogates tumor metastasis via inhibition of
      endocytic activation of the Rho-GTPase Rac1.
AB  - The abundance of the multimeric vacuolar ATP-dependent proton pump, V-ATPase, on
      the plasma membrane of tumor cells correlates with the invasiveness of the tumor
      cell, suggesting the involvement of V-ATPase in tumor metastasis. V-ATPase is
      hypothesized to create a proton efflux leading to an acidic pericellular
      microenvironment that promotes the activity of proinvasive proteases. An
      alternative, not yet explored possibility is that V-ATPase regulates the
      signaling machinery responsible for tumor cell migration. Here, we show that
      pharmacologic or genetic reduction of V-ATPase activity significantly reduces
      migration of invasive tumor cells in vitro. Importantly, the V-ATPase inhibitor
      archazolid abrogates tumor dissemination in a syngeneic mouse 4T1 breast tumor
      metastasis model. Pretreatment of cancer cells with archazolid impairs
      directional motility by preventing spatially restricted, leading edge
      localization of epidermal growth factor receptor (EGFR) as well as of
      phosphorylated Akt. Archazolid treatment or silencing of V-ATPase inhibited Rac1
      activation, as well as Rac1-dependent dorsal and peripheral ruffles by inhibiting
      Rab5-mediated endocytotic/exocytotic trafficking of Rac1. The results indicate
      that archazolid effectively decreases metastatic dissemination of breast tumors
      by impairing the trafficking and spatially restricted activation of EGFR and Rho
      GTPase Rac1, which are pivotal for directed movement of cells. Thus, our data
      reveals a novel mechanism underlying the role of V-ATPase in tumor dissemination.

PMID- 22986743
TI  - Gliomagenesis arising from Pten- and Ink4a/Arf-deficient neural progenitor cells
      is mediated by the p53-Fbxw7/Cdc4 pathway, which controls c-Myc.
AB  - Glioblastoma multiforme is the most common type of primary malignant brain tumor
      and may arise from a cell with neural stem-like properties. Deregulation of the
      retinoblastoma, phosphoinositide-3 kinase (PI3K), and p53 pathways are molecular
      hallmarks of this disease. Recent work has shown that p53(-/-)Pten(-/-) mice form
      gliomas in a c-Myc-dependent manner. To explore the role of the INK4A/ARF locus
      and Pten deletions in gliomagenesis, we generated Pten(-/-)Ink4a/Arf(-/-) mouse
      neural stem cells (mNSC) and such cells were highly proliferative, self-renewing,
      relatively refractory to differentiation, and induced both low- and high-grade
      glioma formation in vivo. In contrast to p53(-/-) Pten(-/-) mNSCs, however, Pten(
      /-)Ink4a/Arf(-/-) mNSCs do not express appreciable levels of c-Myc in vitro,
      although glioma stem cells derived from thesecells did. Sequencing of Pten(-/
      )Ink4a/Arf(-/-) mNSC-derived tumors revealed spontaneous mutations in Tp53 in
      vivo with subsequent downregulation of Fbxw7. Expression of p53 mutants in Pten(
      /-)Ink4a/Arf(-/-) mNSC or knockdown of Fbxw7 resulted in reexpression of c-Myc
      with enhanced Pten(-/-)Ink4a/Arf(-/-) mNSC tumorigenecity. We propose that p53
      mutations contribute to gliomagenesis by both allowing the overexpression of c
      Myc through downregulation of Fbxw7 and by protecting against c-Myc-induced
      apoptosis.

PMID- 22986744
TI  - OTX2 represses myogenic and neuronal differentiation in medulloblastoma cells.
AB  - The brain development transcription factor OTX2 is overexpressed and/or
      genomically amplified in most medulloblastomas, but the mechanistic basis for its
      contributions in this setting are not understood. In this study, we identified
      OTX2 as a transcriptional repressor and a gatekeeper of myogenic and neuronal
      differentiation in medulloblastoma cells. OTX2 binds to the MyoD1 core enhancer
      through its homeobox domain, and the remarkable repressor activity exhibited by
      the homeobox domain renders OTX2 transcriptionally repressive. RNA interference
      mediated attenuation of OTX2 expression triggered myogenic and neuronal
      differentiation in vitro and prolonged the survival in an orthotopic
      medulloblastoma mouse model. Conversely, inducing myogenic conversion of
      medulloblastoma cells led to the loss of OTX2 expression. In medullomyoblastoma,
      a medulloblastoma subtype containing muscle elements, myogenic cells share
      cytogenetic signatures with the primitive tumor cells and OTX2 expression was
      lost in the differentiated myogenic cells. Thus, OTX2 functions via its homeobox
      domain as a suppressor of differentiation, and the loss of OTX2 expression is
      linked to the myogenesis in medullomyoblastoma. Together, our findings illustrate
      the origin of muscle cells in medullomyoblastomas and the oncogenic mechanism of
      OTX2 as a repressor of diverse differentiating potential.

PMID- 22986746
TI  - Hedgehog signaling blockade delays hepatocarcinogenesis induced by hepatitis B
      virus X protein.
AB  - The hepatitis B virus (HBV) encoded X protein (HBx) contributes centrally to the
      pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the
      Hedgehog (Hh) pathway has been linked to many tumor types including HCC. Thus,
      experiments were designed to test the hypothesis that HBx promotes HCC via
      activation of Hh signaling. HBx expression correlated with an upregulation of Hh
      markers in human liver cancer cell lines, in liver samples from HBV infected
      patients with HCC, and in the livers of HBx transgenic mice (HBxTg) that develop
      hepatitis, steatosis, and dysplasia, culminating in the appearance of HCC. The
      findings in human samples provide clinical validation for the in vitro results
      and those in the HBxTg. Blockade of Hh signaling inhibited HBx stimulation of
      cell migration, anchorage-independent growth, tumor development in HBxTg, and
      xenograft growth in nude mice. Results suggest that the ability of HBx to promote
      cancer is at least partially dependent upon the activation of the Hh pathway.
      This study provides biologic evidence for the role of Hh signaling in the
      pathogenesis of HBV-mediated HCC and suggests cause and effect for the first
      time. The observation that inhibition of Hh signaling partially blocked the
      ability of HBx to promote growth and migration in vitro and tumorigenesis in two
      animal models implies that Hh signaling may represent an "oncogene addiction"
      pathway for HBV-associated HCC. This work could be central to designing specific
      treatments that target early development and progression of HBx-mediated HCC.

PMID- 22986748
TI  - Contribution of phytochelatins to cadmium tolerance in peanut plants.
AB  - Cadmium (Cd) is a well known heavy metal considered as one of the most toxic
      metals on Earth, affecting all viable cells that are exposed even at low
      concentration. It is introduced to agricultural soils mainly by phosphate
      fertilizers and causes many toxic symptoms in cells. Phytochelatins (PCs) are non
      protein thiols which are involved in oxidative stress protection and are strongly
      induced by Cd. In this work, we analyzed metal toxicity as well as PCs
      implication on protection of peanut plants exposed to Cd. Results showed that Cd
      exposure induced a reduction of peanut growth and produced changes in the
      histological structure with a deposit of unknown material on the epidermal and
      endodermal cells. When plants were exposed to 10 MUM Cd, no modification of
      chlorophyll, lipid peroxides, carbonyl groups, or hydrogen peroxide (H2O2)
      content was observed. At this concentration, peanut leaves and roots glutathione
      (GSH) content decreased. However, peanut roots were able to synthesize different
      types of PCs (PC2, PC3, PC4). In conclusion, PC synthesis could prevent metal
      disturbance on cellular redox balance, avoiding oxidative damage to
      macromolecules.

PMID- 22986747
TI  - SIRT1 pathway dysregulation in the smoke-exposed airway epithelium and lung tumor
      tissue.
AB  - Cigarette smoke produces a molecular field of injury in epithelial cells lining
      the respiratory tract. However, the specific signaling pathways that are altered
      in the airway of smokers and the signaling processes responsible for the
      transition from smoking-induced airway damage to lung cancer remain unknown. In
      this study, we use a genomic approach to study the signaling processes associated
      with tobacco smoke exposure and lung cancer. First, we developed and validated
      pathway-specific gene expression signatures in bronchial airway epithelium that
      reflect activation of signaling pathways relevant to tobacco exposure, including
      ATM, BCL2, GPX1, NOS2, IKBKB, and SIRT1. Using these profiles and four
      independent gene expression datasets, we found that SIRT1 activity is
      significantly upregulated in cytologically normal bronchial airway epithelial
      cells from active smokers compared with nonsmokers. In contrast, this activity is
      strikingly downregulated in non-small cell lung cancer. This pattern of signaling
      modulation was unique to SIRT1, and downregulation of SIRT1 activity is confined
      to tumors from smokers. Decreased activity of SIRT1 was validated using genomic
      analyses of mouse models of lung cancer and biochemical testing of SIRT1 activity
      in patient lung tumors. Together, our findings indicate a role of SIRT1 in
      response to smoke and a potential role in repressing lung cancer. Furthermore,
      our findings suggest that the airway gene expression signatures derived in this
      study can provide novel insights into signaling pathways altered in the "field of
      injury" induced by tobacco smoke and thus may impact strategies for prevention of
      tobacco-related lung cancer.

PMID- 22986745
TI  - Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1
      and autotaxin.
AB  - Melanoma is the deadliest form of skin cancer in which patients with metastatic
      disease have a 5-year survival rate of less than 10%. Recently, the
      overexpression of a beta-galactoside binding protein, galectin-3 (LGALS3), has
      been correlated with metastatic melanoma in patients. We have previously shown
      that silencing galectin-3 in metastatic melanoma cells reduces tumor growth and
      metastasis. Gene expression profiling identified the protumorigenic gene
      autotaxin (ENPP2) to be downregulated after silencing galectin-3. Here we report
      that galectin-3 regulates autotaxin expression at the transcriptional level by
      modulating the expression of the transcription factor NFAT1 (NFATC2). Silencing
      galectin-3 reduced NFAT1 protein expression, which resulted in decreased
      autotaxin expression and activity. Reexpression of autotaxin in galectin-3
      silenced melanoma cells rescues angiogenesis, tumor growth, and metastasis in
      vivo. Silencing NFAT1 expression in metastatic melanoma cells inhibited tumor
      growth and metastatic capabilities in vivo. Our data elucidate a previously
      unidentified mechanism by which galectin-3 regulates autotaxin and assign a novel
      role for NFAT1 during melanoma progression.

PMID- 22986749
TI  - Field-in-field IMRT versus 3D-CRT of the breast. Cardiac vessels, ipsilateral
      lung, and contralateral breast absorbed doses in patients with left-sided
      lumpectomy: a dosimetric comparison.
AB  - PURPOSE: This study evaluated dose distribution and homogeneity of field-in-field
      intensity-modulated radiation treatment (FIF-IMRT) compared with standard wedged
      tangential-beam 3D conformal radiotherapy (CRT) of the left breast in patients
      who have undergone lumpectomy. Our aim was to improve dose-distribution
      homogeneity in the breast and decrease the dose to organs at risk (OAR), i.e,
      heart and vessels, ipsilateral lung, and contralateral breast. MATERIALS AND
      METHODS: FIF-IMRT and wedge plans of 3D-CRT were carried out for 18 patients with
      cancer of the left breast. Plans were compared according to cumulative dose
      volume histogram (c-DVH) analysis in terms of planned treatment volume (PTV),
      homogeneity index (HI), and conformity index (CI), as well as dose and volume
      parameters of OARs. RESULTS: When the targeted volumes receiving 105 % and 110 %
      of the prescribed dose in the PTV were compared, significant decreases were found
      with the FIF-IMRT technique. With the 105 % dose to the OARs, monitor unit (MU)
      counts were significantly lower with the FIF-IMRT technique. V2 of pulmonary
      artery, left atrium, and aorta and V1 for the contralateral breast were
      statistically significantly lower with FIF-IMRT plans (p = 0.001). PTV showed a
      better HI and CI with FIF-IMRT. CONCLUSIONS: FIF-IMRT enables better dose
      distribution in the PTV and reduces dose to OARs in breast cancer radiotherapy.

PMID- 22986750
TI  - A comparative study between arterial spin labeling and CT perfusion methods on
      hepatic portal venous flow.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility and potential
      usefulness of unenhanced magnetic resonance (MR) hepatic portal perfusion using
      arterial spin labeling (ASL) among healthy volunteers and hepatocellular
      carcinoma patients. MATERIALS AND METHODS: The five healthy volunteers underwent
      unenhanced MR perfusion with inversion time 2 (TI2) values at 500-ms intervals
      between 2,000 and 4,000 ms, and the 12 patients underwent unenhanced MR perfusion
      using ASL and computed tomography (CT) perfusion during superior mesenteric
      artery (SMA) portography. The regions of interest were placed in both the right
      and left lobes of the liver or both the right anterior and posterior segments of
      the liver and were placed over the tumor if a lesion was located within a
      particular perfusion study slice. RESULTS: In the healthy volunteer study,
      perfusion rate in hepatic parenchyma showed a peak at the TI2 value of 3,000 ms
      (254.3 ml/min/100 g +/- 58.3). In patients, a fair correlation was observed
      between CT and MR perfusion (r = 0.795, P < 0.01). CONCLUSION: Our results
      demonstrate a significant fair correlation between unenhanced MR hepatic portal
      perfusion imaging using ASL and CT perfusion during SMA portography.

PMID- 22986751
TI  - Mesenteric cysts associated with recurrent small-bowel volvulus: cause or effect?
AB  - Recurrent small-bowel volvulus is a state of recurrent intermittent or long
      standing persistent twisting of small-bowel loops around its mesentery. The
      association of mesenteric cysts with recurrent small-bowel volvulus as the cause
      or effect is a much debated issue in the literature. We report two cases of
      mesenteric lymphangioma and one case of enteric duplication cyst seen in
      association with recurrent small-bowel volvulus of long duration in absence of
      malrotation.

PMID- 22986752
TI  - Role of ventricular rate response on dementia in cognitively impaired elderly
      subjects with atrial fibrillation: a 10-year study.
AB  - BACKGROUND: The role of ventricular rate response (VRr) on the incidence of
      dementia in elderly subjects with cognitive impairment and atrial fibrillation
      (AF) is not known. Thus, we examined the ability of VRr to predict dementia in
      cognitively impaired elderly subjects with and without AF. METHODS: A total of
      358 cognitively impaired elderly subjects (MMSE <24) with and without AF were
      stratified in low/high (<50/>90) and moderate (>50/<90 bpm) VRr. A 10-year follow
      up was performed. RESULTS: Cognitively impaired subjects with dementia at the end
      of the follow-up were 135 (37.7%): 33 in the presence (75.0%) and 102 (32.5%) in
      the absence of AF (p < 0.001). Multivariate analysis shows that AF is a strong
      predictor of dementia (hazard ratio, HR = 4.10; 95% confidence interval, CI =
      1.80-9.30, p < 0.001). More importantly, low/high VRr (<50/>90 bpm) is predictive
      of dementia in the presence (HR = 7.70, 95% CI = 1.10-14.20, p = 0.03) but not in
      the absence (HR = 1.85; 95% CI = 0.78-4.47; p = 0.152) of AF. CONCLUSIONS: This
      study demonstrates that AF predicts dementia in elderly subjects with cognitive
      impairment. Moreover, VRr seems to play a key role in the incidence of dementia
      in cognitively impaired elderly subjects with AF.

PMID- 22986753
TI  - Meta-analysis shows strong positive association of the TNF-alpha gene with tumor
      stage in bladder cancer.
AB  - There is no consensus on the association between the tumor necrosis factor-alpha
      (TNF-alpha) gene promoter -308 A/G single nucleotide polymorphisms and bladder
      cancer risk. To obtain a more precise estimation of this correlation, we
      conducted a meta-analysis. The PubMed, MEDLINE, Cochrane Library and China
      National Knowledge Infrastructure (CNKI) databases were searched for relevant
      published studies. Seven case-control studies with a total of 1,311 cases and
      1,436 controls were identified and analyzed. A notable correlation was observed
      between the TNF-alpha genotype and bladder cancer grade (AA+GA vs. GG; odds ratio
      1.96, 95% confidence interval 1.37-2.80, p = 0.0002). In summary, this meta
      analysis demonstrates that the TNF-alpha -308 AA+GA genotype may be a marker to
      the tumor-invasive stage of bladder cancer.

PMID- 22986754
TI  - The effect of prone versus supine positioning of Goettingen minipigs on lung
      density as viewed by computed tomography.
AB  - Minipigs are frequently used for scientific research as they are easy to handle
      and the dimensions of their vascular system do not change after 20 months of age.
      Although surgical interventions under anaesthesia are often performed in the
      supine position the effects of this positioning on lung functionality in minipigs
      have not been systematically described. This study aimed to analyse the influence
      of supine positioning on the macrostructure of the lung and the pulmonary density
      by the use of computed tomography imaging in pre-adult Gottingen minipigs. Twelve
      pre-adult female minipigs were used in the study and lung density was
      investigated in both the prone and the supine positions. The time between the
      scans in prone and supine positions was less than 5 minutes (296 +/- 6 sec). In
      the prone position lung density did not differ between the dorsal and ventral
      part of the lung (-641 +/- 72 Hounsfield units [HU]). However in the supine
      position there was a ventrodorsal gradient of decreasing density (ventral part of
      the lung: -497 +/- 106 HU, dorsal part of the lung: -723 +/- 51 HU). The changes
      in lung density were not accompanied by changes in lung volume (829 +/- 191 ml).
      These results suggest an influence of the body position on the
      ventilation/perfusion (V(A)/Q) matching of the lung which could possibly result
      in lowered lung oxygenation as well as in an increased heart activity in the
      supine position. Additionally, due to the steep course of the vena cava caudalis
      from the caval foramen in the diaphragm across to the heart (in contrast to the
      more shallow course in the prone position) the activity of the heart necessary to
      pump the venous blood to the right atrium has to be higher in the supine position
      than in the prone position. In pigs the capacity of the heart to increase
      frequency is limited due to a diastolic/systolic (D/S) ratio <1. Supine
      positioning may possibly increase their risk of cardiovascular complications.

PMID- 22986755
TI  - Contrast-enhanced ultrasound and microcirculation: efficiency through dynamics-
      current developments.
AB  - Ultrasound is often the first imaging modality used in the diagnosis of abdominal
      vascular as well as parenchymal organ pathologies. Contrast-enhanced ultrasound
      (CEUS) enables the dynamic assessment and quantification of microvascularisation
      up to capillary perfusion. Current clinical applications of CEUS are mainly in
      detection and characterization of lesions, particularly benign and malignant
      hepatic and renal lesions, based on differences between lesion and organ
      perfusion. Multifrequency high-resolution transducers are being increasingly
      used, including intra-operatively. Dynamic 3D techniques and ultrasound image
      fusion with CT or MRI may assist the diagnosis and therapy control after
      interventional procedures. Our own studies have demonstrated the excellent
      diagnostic performance of CEUS with perfusion-analysis in the characterization of
      hepatic and renal lesions as well as the assessment of tissue transplant macro-
      and microvascularisation. CEUS opens up new possibilities in the characterization
      of the microvasculature with perfusion analysis, even during the course of
      interventions, thereby providing new possibilities for modified therapeutic
      strategies. In this review, the different new ultrasound techniques with their
      potential applications are described and illustrated.

PMID- 22986756
TI  - Percutaneous irreversible electroporation (IRE) of hepatic malignant tumours:
      contrast-enhanced ultrasound (CEUS) findings.
AB  - PURPOSE: The aim of this study is to describe the image findings of contrast
      enhanced ultrasound (CEUS) after irreversible electroporation (IRE), and to
      assess its usefulness in relation to the evaluation of the ablation status using
      a dynamic recording of the microvascularisation. MATERIAL AND METHOD: In this
      prospectively designed study, a percutaneous IRE was performed for the treatment
      of malignant hepatic lesions in a total of 15 patients following the
      interdisciplinary diagnosis. The lesions were documented using CEUS before,
      immediately after and 20 minutes after the ablation. The acquired CEUS image data
      was subsequently independently retrospectively evaluated by 2 experienced
      radiologists and assessed in relation to microvascularisation using a 5 point
      scale. RESULTS: Using CEUS, a significant reduction in the microcirculation of
      the lesions, both centrally and marginally, could be detected following IRE (p <
      0.001 and p < 0.001). The mean evaluation of the central microcirculation was
      reduced from 3.13 +/- 1.38 to 0.47 +/- 0.64 (p < 0.01). For the peripheral area
      of the lesion and the ablation margin, there was a reduction of 3.37 +/- 1.13 to
      1.57 +/- 0.46 (p = 0.001). There was no significant reduction in the
      macrocirculation. CONCLUSION: Within the framework of this study, it could be
      demonstrated that, in the course of IRE, a rapid significant reduction of the
      microcirculation in the ablation area occurred.

PMID- 22986757
TI  - Four-year-old outcomes of a universal infant-toddler shared reading intervention:
      the let's read trial.
AB  - OBJECTIVE: To determine the emergent literacy and language effects of a low
      intensity literacy promotion program (Let's Read) provided via universal well
      child services to parents during the first 4 years of their child's life. DESIGN:
      Population-based, cluster randomized controlled trial performed between March 1,
      2006, and December 10, 2010. SETTING: Maternal and child health centers
      (clusters) in 5 relatively disadvantaged local government areas in Melbourne,
      Australia. PARTICIPANTS: All parents attending their 4-week well-child
      appointments in participating centers were invited to take part in the study.
      INTERVENTION: The Let's Read program was delivered at 4, 12, 18, and 42 months
      during universal well-child care visits. MAIN OUTCOME MEASURE: Child emergent
      literacy skills (intrasyllabic, phonemic, and sound/letter knowledge) and
      language (core, receptive, and expressive), measured at 4 years of age. RESULTS:
      A total of 630 parents participated, with 365 children in 32 intervention
      clusters and 265 children in 33 control clusters; 563 children (89.4%) were
      retained in the study to 4 years of age. The adjusted mean differences
      (intervention minus control) for emergent literacy was 0.2 (95% CI, -0.2 to 0.6;
      P = .29) for intrasyllabic units, 0.05 (95% CI, -0.4 to 0.5; P = .85) for
      phonemic awareness, and 0.1 (95% CI, -1.5 to 1.6; P = .92) for letter knowledge.
      For language, the differences were 1.6 (95% CI, -1.1 to 4.3; P = .25) for core,
      0.8 (95% CI, -2.0 to 3.7; P = .56) for receptive, and 1.4 (95% CI, -1.4 to 4.2; P
      = .32) for expressive scores. CONCLUSION: This population-wide primary care
      literacy promotion and book distribution program provided neither the anticipated
      benefits to literacy and language nor enhanced uptake of literacy activities at 4
      years of age, even when targeted to relatively disadvantaged areas. TRIAL
      REGISTRATION: isrctn.org Identifier: ISRCTN04602902.

PMID- 22986758
TI  - Interleukin-1B promoter (-31T/C and -511C/T) polymorphisms in paranoid
      schizophrenia.

PMID- 22986759
TI  - Novel infectious agent-free hemostatic material (TDM-621) in cardiovascular
      surgery.
AB  - SUBJECTS: Currently, hemostatic materials made from human blood components and
      animal-derived collagen is used for controlling operative hemorrhage in the
      cardiovascular surgery field. In this study, we focused on an entirely synthetic
      self-assembling peptide (development code: TDM-621) that gels when in contact
      with blood or other bodily fluids and stops bleeding upon contact with a wound
      site. We investigated its usefulness as a hemostatic material in animal and
      clinical studies. METHODS: Before we began the clinical study, we demonstrated
      the hemostasis efficacy and safety of TDM-621 in animal experimental models.
      Twenty-five patients (22 men, 3 women) were enrolled in the clinical study, and
      the following procedures were performed: 1) coronary artery bypass graft (CABG)
      (n = 9), 2) abdominal aortic graft replacement (n = 4), and 3) peripheral artery
      bypass (n = 12). The TDM-621 material was applied to a total of 33 vascular
      anastomotic graft sites (some patients received material at more than one site).
      Both hemostatic efficacy and safety were examined. RESULTS: A total of 33
      anastomotic graft sites in 25 patients were evaluated, and the averaged primary
      and secondary efficacy rate was 94.5%. No postoperative bleeding or adverse
      events (including serious adverse events) with a causal relationship to treatment
      were observed. CONCLUSION: This study indicated that TDM-621 is a more effective
      and reliable hemostat than commonly-used general hemostatic agents and,
      therefore, will be very useful in several cardiovascular surgery applications.

PMID- 22986760
TI  - Inkjet printing of protein microarrays on freestanding polymeric nanofilms for
      spatio-selective cell culture environment.
AB  - In the last years, an increasing interest in bio-hybrid systems for what concerns
      the precise control of cell-material interactions has emerged. This trend leads
      towards the development of new nano-structured devices such as bioMEMS, tissue
      engineering scaffolds, biosensors, etc. In the present study, we focused on the
      development of a spatio-selective cell culture environment based on the inkjet
      printing of bio-patterns on polymeric ultra-thin films (nanofilms) composed of
      poly(methylmethacrylate) (PMMA). Freestanding PMMA nanofilms having hundreds-of
      nm thickness were prepared by spin-coating. Different shapes of cell adhesion
      promoters such as poly (L-lysine) (PLL) were micropatterned by inkjet printing.
      Moreover, to promote cell adhesion, the surface of PLL microarrays was modified
      with fibronectin via electorostatic interaction. The selective deposition of
      C2C12 skeletal muscle cells was confirmed and their viability was qualitatively
      assessed after 24 h. The combination of muscular cells with protein
      micropatterned freestanding nanofilm is beneficial for the implementation of new
      bio-hybrid system in muscular tissue engineering.

PMID- 22986761
TI  - A teaching-learning initiative with tablet computing.

PMID- 22986762
TI  - Longitudinal care planning and coordination in long-term and post-acute care
      settings.

PMID- 22986764
TI  - Measurement properties of outcome measures for vitiligo. A systematic review.
AB  - OBJECTIVE To summarize and critically appraise the evidence on the measurement
      properties of clinician-, patient-, and observer-reported outcomes, measuring any
      construct of interest in patients with all types of vitiligo. DATA SOURCES
      Electronic databases including PubMed (1948 to July 2011), OVID EMBASE (1980 to
      July 2011), and CINAHL (EBSCOhost) (1982 to July 2011) were searched. STUDY
      SELECTION Two authors independently screened all records for eligibility. For
      inclusion, the study population had to include patients with vitiligo, for which
      outcome measures were developed or evaluated on their measurement properties. The
      initial search retrieved 1249 records, of which 14 articles met the inclusion
      criteria. DATA EXTRACTION Characteristics of the included instruments, study
      population, and results of the measurement properties were extracted. The
      Consensus-Based Standards for the Selection of Health Status Measurement
      Instruments (COSMIN) 4-point checklist, combined with quality criteria for
      measurement properties, was used to calculate the overall level of evidence per
      measurement property of each instrument. Independent extraction and assessment
      was performed by 2 authors. DATA SYNTHESIS Eleven different measurement
      instruments were identified. Strong evidence was found for a positive internal
      consistency of the Dermatology Life Quality Index. For other instruments, the
      evidence of measurement properties was limited or unknown. CONCLUSIONS
      Recommendations on the use of specific outcome measures for vitiligo should be
      formulated with caution because current evidence is insufficient owing to a low
      number of studies with poor methodological quality and unclear clinical
      relevance. To recommend outcome measures for vitiligo, further research on
      measurement properties of clinical relevant outcome measures for vitiligo
      according to COSMIN quality criteria is needed.

PMID- 22986765
TI  - Iatrogenic peroneal artery pseudoaneurysm treated by transluminal coil
      embolization.
AB  - An 82-year-old male presented to our institution with sudden onset pain in the
      bilateral lower extremities. Emergent angiography showed thrombus in the right
      common femoral and left popliteal arteries. Thromboembolectomy was performed
      using a Fogarty-balloon catheter through the bilateral femoral arteriotomy. A few
      hours later, he complained of pain in the left calf. Emergent angiography showed
      a 3.6 * 2.4 cm pseudoaneurysm at the peroneal artery (PA). Coil embolization to
      the pseudoaneurysm of PA was performed with 8 coils. It is considered that use of
      the Fogarty-balloon catheter without angiographic guidance caused the
      pseudoaneurysm for this case. Endovascular coil embolization for a PA
      pseudoaneurysm is safer, less invasive and more effective.

PMID- 22986766
TI  - The impact of cerium oxide nanoparticles on tomato (Solanum lycopersicum L.) and
      its implications for food safety.
AB  - Sustainable development of nanotechnology requires an understanding of the long
      term ecotoxicological impact of engineered nanomaterials on the environment.
      Cerium oxide nanoparticles (CeO2-NPs) have great potential to accumulate and
      adversely affect the environment owing to their widespread applications in
      commercial products. This study documented the chronic phenotypic response of
      tomato plants to CeO2-NPs (0.1-10 mg L-1) and determined the effect of CeO2-NPs
      on tomato yield. The results indicated that CeO2-NPs at the concentrations
      applied in this study had either an inconsequential or a slightly positive effect
      on plant growth and tomato production. However, elevated cerium content was
      detected in plant tissues exposed to CeO2-NPs, suggesting that CeO2-NPs were
      taken up by tomato roots and translocated to shoots and edible tissues. In
      particular, substantially higher Ce concentrations were detected in the fruits
      exposed to 10 mg L-1 CeO2-NPs, compared with controls. This study sheds light on
      the long term impact of CeO2-NPs on plant health and its implications for our
      food safety and security.

PMID- 22986767
TI  - Granulomatous disease in CVID: retrospective analysis of clinical characteristics
      and treatment efficacy in a cohort of 59 patients.
AB  - BACKGROUND: Granulomatous disease (GD) will develop in a subset of patients with
      common variable immunodeficiency (CVID). Little is known about the efficacy of
      therapeutic agents used for treating this disorder. OBJECTIVE: To evaluate the
      efficacy of immunosuppressive drugs with the help of a set of clinical,
      biological and radiological criteria. METHOD: Clinical and laboratory features of
      CVID patients were collected from the French DEFI cohort, a prospective study on
      adults with hypogammaglobulinemia. The medical charts of 55 patients (93 %) of
      the GD cohort were reviewed. RESULTS: Among 436 subjects with CVID, 59 patients
      (13.5 %) were diagnosed with GD. Of the 55 patients in whom medical charts were
      available, 32 patients received treatment for the granulomatous disease.
      Corticosteroids were the most frequently used drug. Complete response to
      treatment was infrequent. It was achieved with corticosteroids, cyclophosphamide,
      hydroxychloroquine, rituximab and methotrexate. Azathioprine, cyclosporine,
      mycophenolate mofetil, sirolimus, infliximab and thalidomide led to partial or
      absence of response. Complete and partial responses were observed in lymph nodes,
      lungs, liver, skin, bone marrow and central nervous system. Absent of response
      for gastrointestinal tract granulomas was noted in all cases of treatment
      attempt. CONCLUSION: CVID patients with GD exhibit a particular biological
      phenotype. Treatment should be considered in any symptomatic patient or if there
      is evidence of organ dysfunction. Corticosteroids are the drug of choice in most
      instances but response to treatment is often unsatisfactory.

PMID- 22986768
TI  - Life events and difficulties and their association with antenatal distress in
      White and South Asian women in the UK.
AB  - PURPOSE: Symptoms of distress during pregnancy are common and often go unnoticed.
      There is a well-established relation between life events and depression. The
      current study aims to explore the association between life events and
      difficulties, and symptoms of emotional and somatic distress during pregnancy in
      White and South Asian women in the UK. METHODS: 100 pregnant women attending
      routine antenatal appointments were interviewed using the Life Events and
      Difficulties Schedule (LEDS). We investigated the frequency and type of events
      experienced in the year prior to conception and during pregnancy, as predictors
      for somatic and emotional distress, measured using the GHQ-28. RESULTS: Non
      severe stressors accounted for over 90 % of those reported, half of which (43-53
      %) were health and reproduction-related. Somatic symptoms were associated with
      the number of non-severe events, and number of children and emotional symptoms
      were associated with non-marked difficulties. There was little evidence of an
      association between severe events and distress. Ethnicity had little effect on
      any associations although South Asian women were at slightly higher odds of
      experiencing emotional symptoms, which appear to be buffered by social support.
      CONCLUSIONS: In routine antenatal care it is important to assess both emotional
      and somatic symptoms. Health professionals need to be sensitive to the health,
      social, cultural and environmental circumstances of women during pregnancy and
      ensure appropriate support is in place, particularly for multi-parous women.
      Regression models explained a small but significant amount of the variance in
      distress symptoms. Further work is necessary to explore other contributory
      factors and also the mechanisms through which stressors have their effect.

PMID- 22986769
TI  - Evidence-based current surgical practice: calculous gallbladder disease.
AB  - BACKGROUND: Gallbladder disease is common and, if managed incorrectly, can lead
      to high rates of morbidity, mortality, and extraneous costs. The most common
      complications of gallstones include biliary colic, acute cholecystitis, common
      bile duct stones, and gallstone pancreatitis. Ultrasound is the initial imaging
      modality of choice. Additional diagnostic and therapeutic studies including
      computed tomography, magnetic resonance imaging, magnetic resonance
      cholangiopancreatography, endoscopic ultrasound, and endoscopic retrograde
      cholangiopancreatography are not routinely required but may play a role in
      specific situations. DISCUSSION: Biliary colic and acute cholecystitis are best
      treated with early laparoscopic cholecystectomy. Patients with common bile duct
      stones should be managed with cholecystectomy, either after or concurrent with
      endoscopic or surgical relief of obstruction and clearance of stones from the
      bile duct. Mild gallstone pancreatitis should be treated with cholecystectomy
      during the initial hospitalization to prevent recurrence. Emerging techniques for
      cholecystectomy include single-incision laparoscopic surgery and natural orifice
      transluminal endoscopic surgery. Early results in highly selected patients
      demonstrate the safety of these techniques. The management of complications of
      the gallbladder should be timely and evidence-based, and choice of procedures,
      particularly for common bile duct stones, is largely influenced by facility and
      surgeon factors.

PMID- 22986771
TI  - MR imaging characteristics of soft tissue vascular anomalies in children.
AB  - Accurate classification of soft tissue vascular anomalies is critical since
      treatment options and morbidity differ significantly for the various groups of
      vascular anomalies (VA). A classification system introduced by Mulliken and
      Glowacki in 1982 explained the biology of VA, thus resulting in improved
      management and communication between different disciplines taking care of
      children with soft tissue vascular anomalies. This classification has been
      updated by the International Society for the Study of Vascular Anomalies in 1996
      and forms the basis for the current nomenclature. Although the majority of
      vascular anomalies can be accurately classified by their clinical history and a
      physical exam, imaging is necessary to determine the full anatomical extent of
      the anomaly, to follow up treatment response, to confirm diagnosis, and to
      provide correct classification in challenging cases when necessary. This article
      will review the key magnetic resonance imaging (MRI) features of most common soft
      tissue vascular anomalies in children. MRI and dynamic contrast-enhanced magnetic
      resonance angiography are crucial for the evaluation of vascular anomalies in
      children because of lack of radiation, high soft tissue resolution, and the
      capability of dynamic contrast-enhanced images to reflect the hemodynamics of the
      anomalies.

PMID- 22986770
TI  - Abnormal striatal circuitry and intensified novelty seeking among adolescents who
      abuse methamphetamine and cannabis.
AB  - It has been hypothesized that changes in striatal-mediated dopamine modulation
      during adolescence may increase the risk for initiating substance abuse as a
      result of its fundamental role in arbitrating reward sensitivity and motivation
      during learning and decision making. However, substance abuse during adolescence
      may also significantly modify striatal structure and function and concomitantly
      alter reward sensitivity and action control while this brain region is undergoing
      remodeling. In the present investigation, to assess the relationship of
      methamphetamine (Meth) or Meth and cannabis (CA) abuse to regional striatal
      morphology, we acquired structural magnetic resonance images, using a 3T Siemens
      Trio scanner, from three groups of adolescents composed of healthy controls (n =
      10), Meth abusers (n = 9) and combined Meth and CA abusers (Meth+CA, n = 8). We
      also assessed novelty seeking using the novelty seeking subscale of Cloninger's
      Tridimensional Character Inventory. The results indicate that adolescent Meth+CA
      abusers have increased regional striatal volume and show intensified novelty
      seeking in contrast to the controls. The degree of Meth exposure was also
      positively correlated with regional striatal volume and novelty seeking in both
      the Meth and Meth+CA users. These preliminary findings support theories that
      propose a role for the striatum in adolescent substance abuse and further
      indicate that novelty seeking may be related to the initiation of, or sustained,
      drug use.

PMID- 22986772
TI  - Simultaneous EMG-fMRI during startle inhibition in monosymptomatic enuresis--an
      exploratory study.
AB  - Evidence is growing that monosymptomatic enuresis (ME) is a maturational disorder
      of the central nervous system with a lack of arousal and lacking inhibition of
      the micturition reflex. Previous studies have shown a significant reduction of
      prepulse inhibition (PPI) of startle in children with enuresis. However, it is
      still unclear whether the abnormal PPI in enuresis is based on an inhibitory
      deficit at brainstem or cortical level. Nine children with ME and ten healthy
      children were investigated using simultaneous recording of EMG from the M.
      orbicularis oculi and functional MRI. The experimental paradigm consisted of
      acoustic startle stimulation, with startle-alone stimuli and prepulse-startle
      combinations. Functional MRI data were processed using multiple regression and
      parametric modulation with startle amplitudes as a parameter. Neither patients
      with enuresis nor healthy children revealed measurable PPI in the MRI scanner.
      Startle stimuli caused equal hemodynamic changes in the acoustic cortex, medial
      prefrontal and orbitofrontal cortex in both groups. The amplitude of startle
      correlated with more prominent BOLD signal changes in the anterior cingulate
      cortex in healthy subjects than in patients with ME. This pronounced frontal
      activation in healthy controls was related to the PPI condition, indicating that
      the prefrontal cortex of healthy children was activated more strongly to inhibit
      startle than in patients with ME. In conclusion, apart from the possibility that
      recordings of PPI inside the MRI scanner may be compromised by methodological
      problems, the results of this study suggest that high cortical control mechanisms
      at the prefrontal level are relevant for the pathogenesis of ME.

PMID- 22986773
TI  - Nationwide study of childhood celiac disease incidence over a 35-year period in
      Estonia.
AB  - The aims of the study were to analyze the trends and characteristics of the
      incidence and clinical presentation of childhood celiac disease (CD) from 1976 to
      2010 in Estonia. The study included all children up to 19 years of age diagnosed
      with small bowel biopsy proven CD. During a 35-year period, CD was diagnosed in
      152 children in Estonia (68 boys, median age 2.3 years). From 1976 to 1980, the
      age-standardized incidence rate of CD was 0.10 per 100,000 person-years. After
      the introduction of gliadin and endomysium antibody screening (in conjunction
      with activities directed to increase the physicians awareness), the incidence
      rate increased from 0.48 in 1986-1990 to 1.55 per 100,000 person-years in 1991
      1995. After initiating screening with anti-tissue transglutaminase antibodies in
      2003 and routine screening for CD among all children with newly diagnosed type 1
      diabetes in 2005, the incidence rate increased from 1.59 in 2001-2005 to 3.14 per
      100,000 person-years in 2006-2010 (median age 6.8 years). Our nationwide study
      demonstrates a more than 30-fold increase in the incidence of childhood CD over a
      35-year period in Estonia, along with changing patterns in the presentation of
      pediatric CD. In addition to the impact of use of novel CD screening methods,
      active search and rising of the awareness among doctors may have strongest
      effect. Both environmental and social factors could be also involved in the
      increase in CD incidence.

PMID- 22986774
TI  - A nickel containing polyoxometalate water oxidation catalyst.
AB  - A new pentanickel silicotungstate complex,
      K(10)H(2)[Ni(5)(OH)(6)(OH(2))(3)(Si(2)W(18)O(66))].34H(2)O (KH-), has been
      synthesized and characterized by X-ray crystallography and several other methods.
      Dynamic light scattering, kinetics and other experiments confirm that in the
      presence of [Ru(bpy)(3)](2+) (the photosensitizer for light-driven water
      oxidations) and [Ru(bpy)(3)](3+) (the oxidant in the dark water oxidations)
      exists in an equilibrium between solution (soluble) and a [Ru(bpy)(3)](n+)-
      complex (minimally soluble) form. This new pentanickel polyoxometalate catalyzes
      efficient water oxidation in both the dark and on irradiation with 455 nm LED
      light with 1.0 mM [Ru(bpy)(3)](2+) photosensitizer and 5.0 mM Na(2)S(2)O(8),
      sacrificial electron acceptor. Four lines of evidence indicate that in this
      solution [symbol:see text] Ru(bpy)(3)](n+)- complex equilibrium remains molecular
      and does not decompose to nickel hydroxide particles.

PMID- 22986775
TI  - Lost and forgotten? Orientation versus memory in Alzheimer's disease and
      frontotemporal dementia.
AB  - Recent studies suggest that significant memory problems are not specific to
      Alzheimer's disease (AD) but can be also observed in other neurodegenerative
      conditions, such as behavioral variant frontotemporal dementia (bvFTD). We
      investigated whether orientation (spatial & temporal) information is a better
      diagnostic marker for AD compared to memory and whether their atrophy correlates
      of orientation and memory differ. A large sample (n = 190) of AD patients (n =
      73), bvFTD patients (n = 54), and healthy controls (n = 63) underwent testing. A
      subset of the patients (n = 72) underwent structural imaging using voxel-based
      morphometry analysis of magnetic resonance brain imaging. Orientation and memory
      scores from the Addenbrooke's Cognitive Examination showed that AD patients had
      impaired orientation and memory, while bvFTD patients performing at control level
      for orientation but had impaired memory. A logistic regression showed that 78% of
      patients could be classified on the basis of orientation and memory scores alone
      at clinic presentation. Voxel-based morphometry analysis was conducted using
      orientation and memory scores as covariates, which showed that the neural
      correlates for orientation and memory also dissociated with posterior hippocampus
      cortex being related to orientation in AD, while the anterior hippocampus was
      associated with memory performance in the AD and bvFTD patients. Orientation and
      memory measures discriminate AD and bvFTD to a high degree and tap into different
      hippocampal regions. Disorientation and posterior hippocampus appears therefore
      specific to AD and will allow clinicians to discriminate AD patients from other
      neurodegenerative conditions with similar memory deficits at clinic presentation.

PMID- 22986776
TI  - Confirmation of the amyloidogenic process in posterior cortical atrophy: value of
      the Abeta42/Abeta40 ratio.
AB  - Posterior cortical atrophy (PCA) is characterized by progressive higher-order
      visuo-perceptual dysfunction and praxis declines. This syndrome is related to
      several underlying diseases, including Alzheimer's disease (AD), sometimes
      involving an amyloidogenic process. The aims of the study were to 1) define
      cerebrospinal fluid (CSF) biomarker profiles in PCA patients compared to AD
      patients and 2) explore the amyloidogenic process through the Abeta(42)/Abeta(40)
      ratio in PCA patients to elucidate the underlying disease in vivo. CSF biomarker
      analysis (t-tau, p-tau, Abeta(42), and Abeta(42)/Abeta(40) ratio) and
      neuropsychological examination were performed in 22 PCA patients and compared
      with those of age-matched AD patients. Associated clinical neurological signs
      were investigated (e.g., extrapyramidal motor signs, myoclonus). CSF biomarker
      profiles did not differ significantly between the PCA and AD groups; 82% of
      patients with PCA fulfilled the biological criteria for typical AD with abnormal
      levels of the three markers and 18% of PCA patients presented atypical CSF
      profiles. All PCA patients with associated clinical neurological signs presented
      typical AD CSF profiles. The clinical presentations of these patients were
      similar to other PCA subjects. The Abeta(42)/Abeta(40) ratio for all PCA
      patients, including those with atypical CSF profiles, was decreased. Most PCA
      syndromes were associated with CSF biomarkers suggestive of AD, even in cases
      with associated clinical neurological signs. The amyloidogenic process was
      confirmed by the decreased Abeta(42)/Abeta(40) ratio for all patients. This
      analysis avoids misdiagnosis in the presence of physiologically high or low
      amyloid peptide production rates and provides information in vivo to improve
      understanding of the underlying disease in PCA.

PMID- 22986777
TI  - Triptolide inhibits amyloid-beta production and protects neural cells by
      inhibiting CXCR2 activity.
AB  - Triptolide, a biologically active natural product from Tripterygium wilfordii,
      protects neurons from inflammation-mediated damage. Our results showed for the
      first time that triptolide inhibited the expression of CXCR2 and presenilin in a
      neuroblastoma cell line SHSY5Ysw. Moreover, triptolide potently inhibited amyloid
      beta1-42 production with IC50 value of 30 pM in HEK293sw cells or 2 nM in
      SHSY5Ysw cells, respectively. We also demonstrated that triptolide prevented
      primary cortical neurons from chemokine CXCL1-induced cytotoxicity. Therefore,
      our study indicates that the neural protective effect of triptolide is largely
      mediated by inhibiting CXCR2 activity.

PMID- 22986778
TI  - Structural brain signature of FTLD driven by Granulin mutation.
AB  - Several causative gene mutations have been identified in frontotemporal lobar
      degeneration (FTLD), including mutations within Granulin (GRN) genes. It was
      recently shown that FTLD patients carriers of GRN Thr272fs mutation [FTLD
      GRN(m+)] exhibit more severe abnormalities, as assessed by magnetic resonance
      imaging (MRI), than those with sporadic FTLD [FTLD-GRN(m-)]. The aim of this
      study was to investigate the relationship between grey (GM) and white matter (WM)
      microstructural damage in FTLD patients, carriers and non-carriers of the
      mutation. Twenty-three FTLD patients [6 GRN(m+) and 17 GRN(m-)] and 12 healthy
      subjects received an MRI scan including volumetric and diffusion imaging. GM was
      assessed using voxel-based morphometry, while the corpus callosum was
      reconstructed using diffusion tractography. Mean diffusivity and fractional
      anisotropy of the corpus callosum were compared between groups. FTLD patients
      showed widespread GM atrophy and altered diffusion indices in the corpus callosum
      when compared to healthy subjects. When contrasting GRN(m+) against GRN(m-)
      patients, the former group had more atrophy in the left frontal GM, and reduced
      fractional anisotropy and increased mean diffusivity in the left anterior part of
      the corpus callosum. Significant correlations between the GM and WM damage were
      found in GRN(m+) patients. This pattern of damage was able to predict some of the
      additional neuropsychological deficits observed in GRN(m+) as compared to GRN(m-)
      patients. A more prominent involvement of WM in GRN(m+) patients is consistent
      with the knowledge that GRN genes are expressed in the microglia. This
      involvement might be responsible for the accrual of additional GM atrophy via
      disconnection mechanisms.

PMID- 22986779
TI  - A modest proposal for a longitudinal study of dementia prevention (with apologies
      to Jonathan Swift, 1729).
AB  - Many studies have documented the role of risk and protective factors for late
      life dementing illnesses, particularly Alzheimer's disease. A "Systematic Review"
      from the US Agency for Healthcare Research and Quality and the National Institute
      on Aging concluded that because the overall quality of evidence was low,
      recommendations for public health could not be made. In order to gain evidence
      for the efficacy of lifestyle interventions, we propose a "Modest Proposal" to
      study 10,000 subjects over 40 years randomly assigned to groups of low or high
      saturated fat in the diet, head injury, and high or low levels of mental
      activity, physical activity, or inactivity as well as smoking or non-smoking.
      This proposed study cannot be accomplished. The "Modest Proposal" illustrates
      that the absence of definitive evidence should not restrict physicians from
      making reasonable recommendations based on the evidence that is available.

PMID- 22986780
TI  - SorLA deficiency dissects amyloid pathology from tau and cholinergic
      neurodegeneration in a mouse model of Alzheimer's disease.
AB  - Sortilin-related receptor with A-type repeats (SorLA, also known as LR11) has
      been implicated in Alzheimer's disease (AD). Thus, genetic studies associated
      SorLA gene variants with the risk of sporadic AD. Also, in vitro and in vivo
      studies showed that SorLA impairs processing of the amyloid-beta protein
      precursor (AbetaPP) to amyloid-beta. In particular, it has been found that loss
      of SorLA accelerates senile plaque deposition in mouse models overexpressing
      mutant forms of human AbetaPP and presenilin 1. Here we tested the possibility
      that SorLA deficiency also interferes with behavioral and neuropathological
      endpoints in an alternative murine AD model, the AD10 anti-nerve growth factor
      (NGF) mouse, in which amyloid-beta accumulation derives from the altered
      processing of endogenous AbetaPP. In addition to alterations in AbetaPP
      processing, AD10 mice also show cholinergic deficit and tau hyperphosphorylation
      resulting in behavioral deficits in learning and memory paradigms. We found that
      the loss of SorLA not only exacerbates early amyloid pathology but, at the same
      time, protects from cholinergic deficit and from early phospho-tau
      mislocalization. The results show that in the AD10 anti-NGF mouse model the
      AbetaPP processing-related aspects of neurodegeneration can be dissociated from
      those related to tau posttranslational processing and to cholinergic phenotypic
      maintenance by modulation of SorLA expression. We suggest that SorLA regulates
      different aspects of neurodegeneration in a complex way, supporting the
      hypothesis that SorLA expression might be critical not only for amyloid-related
      pathology but also for other cellular processes altered in AD.

PMID- 22986781
TI  - A brief history of Alzheimer's disease gene discovery.
AB  - The rich and colorful history of gene discovery in Alzheimer's disease (AD) over
      the past three decades is as complex and heterogeneous as the disease, itself.
      Twin and family studies indicate that genetic factors are estimated to play a
      role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous
      pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant
      for early-onset (<60 years) familial AD, which represents <5% of AD. On the other
      hand, common gene polymorphisms, such as the 4 and 2 variants of the APOE gene,
      influence susceptibility for common (>95%) late-onset AD. These four genes
      account for 30-50% of the inheritability of AD. Genome-wide association studies
      have recently led to the identification of additional highly confirmed AD
      candidate genes. Here, I review the past, present, and future of attempts to
      elucidate the complex and heterogeneous genetic underpinnings of AD along with
      some of the unique events that made these discoveries possible.

PMID- 22986782
TI  - Volumetric brain changes in thalamus, corpus callosum and medial temporal
      structures: mild Alzheimer's disease compared with amnestic mild cognitive
      impairment.
AB  - BACKGROUND: It is widely known that atrophy of medial temporal structures is
      present in the mild stage of Alzheimer's disease (AD) and amnestic mild cognitive
      impairment (aMCI). However, structures such as the thalamus and corpus callosum
      are much less studied. METHODS: We compared the volumes of the entorhinal cortex,
      hippocampus, thalamus and the corpus callosum in 14 controls, 14 patients with
      mild AD and 15 with aMCI and correlated these volumes with neuropsychological
      data. MRI was obtained at 2 T followed by manual segmentation. RESULTS: We found
      atrophy in hippocampi and thalami of MCI patients compared to controls, and in
      the bilateral entorhinal cortex of aMCI compared to AD patients. All the
      structures showed atrophy in AD patients compared to controls, including the
      corpus callosum. CONCLUSIONS: Our study confirms that thalamic areas are
      atrophied in aMCI, and the corpus callosum might represent a good structural
      marker for mild AD. Those areas were associated with cognitive functions already
      described in the literature.

PMID- 22986783
TI  - Association between intensive handwashing promotion and child development in
      Karachi, Pakistan: a cluster randomized controlled trial.
AB  - OBJECTIVE: To evaluate associations between handwashing promotion and child
      growth and development. DESIGN: Cluster randomized controlled trial. SETTING:
      Informal settlements in Karachi, Pakistan. PARTICIPANTS: A total of 461 children
      who were enrolled in a trial of household-level handwashing promotion in 2003 and
      were younger than 8 years at reassessment in 2009. INTERVENTIONS: In 2003,
      neighborhoods were randomized to control (n = 9), handwashing promotion (n = 9),
      or handwashing promotion and drinking water treatment (n = 10); intervention
      households received free soap and weekly handwashing promotion for 9 months. MAIN
      OUTCOME MEASURES: Anthropometrics and developmental quotients measured with the
      Battelle Developmental Inventory II at 5 to 7 years of age. RESULTS: Overall,
      24.9% (95% CI, 20.0%-30.6%) and 22.1% (95% CI, 18.0%-26.8%) of children had z
      scores that were more than 2 SDs below the expected z scores for height and body
      mass index for age, respectively; anthropometrics did not differ significantly
      across study groups. Global developmental quotients averaged 104.4 (95% CI, 101.9
      107.0) among intervention children and 98.3 (95% CI, 93.1-103.4) among control
      children (P = .04). Differences of similar magnitude were measured across
      adaptive, personal-social, communication, cognitive, and motor domains.
      CONCLUSIONS: Although growth was similar across groups, children randomized to
      the handwashing promotion during their first 30 months of age attained global
      developmental quotients 0.4 SDs greater than those of control children at 5 to 7
      years of age. These gains are comparable to those of at-risk children enrolled in
      publicly funded preschools in the United States and suggest that handwashing
      promotion could improve child well-being and societal productivity. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01538953.

PMID- 22986784
TI  - The association of plasma fluorescent oxidation products and chronic kidney
      disease: a case-control study.
AB  - BACKGROUND/AIMS: Plasma fluorescent oxidation products (FLOP) constitute a stable
      and easily measured biomarker of cumulative oxidative stress. However, their
      association with chronic kidney disease (CKD) has not been studied. METHODS: We
      examined the association of FLOP and CKD in 201 CKD patients and 201 controls
      without CKD from the community. CKD was defined as an estimated glomerular
      filtration rate (eGFR) <60 ml/min/1.73 m(2) or the presence of albuminuria.
      RESULTS: Adjusted median (interquartile range) FLOP levels were significantly
      higher in patients with CKD than in controls [FLOP1 (lipid oxidation products):
      215.2 (181.3-268.7) vs. 156.6 (139.6-177.3) fluorescent intensity units/ml, p <
      0.0001; FLOP2 (DNA oxidation products): 534.8 (379.3-842.4) vs. 269.9 (232.4
      410.5) fluorescent intensity units/ml, p < 0.0001; FLOP3 (protein and
      phospholipid oxidation products): 51.4 (44.4-66.0) vs. 45.2 (38.3-51.7)
      fluorescent intensity units/ml, p = 0.002]. Compared with those with a FLOP level
      below the 75th percentile, participants with a FLOP level above the 75th
      percentile had increased odds of CKD after adjustment for covariables (FLOP1:
      odds ratio 13.1, 95% confidence interval 6.2-27.6; FLOP2: odds ratio 5.7, 95%
      confidence interval 2.9-11.1; FLOP3: odds ratio 2.4, 95% confidence interval 1.2
      4.7). Levels of FLOP1, FLOP2 and FLOP3 were related to eGFR (p < 0.0001 for all)
      and log-transformed urine albumin (p < 0.005 for all) in multivariable-adjusted
      linear regression models. CONCLUSION: These data indicate that an elevated FLOP
      level is associated with CKD status and severity. Future studies are warranted to
      elucidate its role in the development and progression of CKD.

PMID- 22986785
TI  - Lack of hepatic c-Met and gp130 expression is associated with an impaired
      antibacterial response and higher lethality after bile duct ligation.
AB  - The prognosis of liver failure is often determined by infectious and cholestatic
      complications. As HGF/c-Met and interleukin (IL)-6/gp130 control hepatic
      cytoprotective pathways, we here investigated their cooperative role during the
      onset of cholestatic liver injury. Conditional hepatocyte-specific ((Deltahepa))
      c-Met, gp130 and c-Met/gp130 knockout mice (Cre-loxP system) were subjected to
      bile duct ligation (BDL) and lipopolysaccharide (LPS) stimulation.
      gp130(Deltahepa) and c-Met/gp130(Deltahepa) mice displayed increased lethality
      associated with severe bacteraemia early after BDL, whereas c-Met(Deltahepa) and
      wild-type mice showed normal survival. Analysis of the innate immune response and
      the regulation of hepatic antibacterial pathways showed that the LPS-triggered
      hepatocellular response via the Toll-like receptor-4 pathway was regulated
      differentially by HGF/c-Met and IL-6/gp130. Activation of p38MAPK, c-Jun N
      terminal kinase and signalling transducer and activator of transcription-3 was
      impaired in gp130(Delta) and c-Met(Deltahepa) livers. In addition, the acute
      phase response (APR) was reduced in c-Met(Deltahepa) livers, whereas
      gp130(Deltahepa) displayed a completely abolished APR. In contrast, TNF-alpha
      dependent NF-kappaB activation was enhanced in gp130(Deltahepa) and c
      Met(Deltahepa) mice and it was associated with a higher rate of apoptosis and
      inflammation. Moreover, expression of the neutrophil produced and secreted
      cathelin-related antimicrobial peptide and of genes related to the inflammasome
      complex correlated with the strength of the bacterial infection and with TNF
      alpha expression. In conclusion, Gp130 and c-Met are involved in the hepatic
      antibacterial and innate immune response, control the APR and thus prevent sepsis
      and liver injury during cholestatic conditions.

PMID- 22986786
TI  - Impaired post-infarction cardiac remodeling in chronic kidney disease is due to
      excessive renin release.
AB  - The complex pathophysiological interactions between heart and kidney diseases are
      collectively known as cardiorenal syndrome. The renin-angiotensin system (RAS)
      may have a pivotal role in the development of cardiorenal syndrome. The aim of
      this study was to elucidate the RAS activity responsible for adverse post
      infarction remodeling and prognosis in mice with renal failure. To establish the
      type IV cardiorenal syndrome model, 5/6 nephrectomy (NTX) was performed in a
      surgical procedure, followed by the induction of myocardial ischemia (MI) by a
      coronary artery ligation 4 weeks later. NTX and MI resulted in deteriorated left
      ventricular remodeling and RAS activation, which was improved by an aliskiren
      that appeared to be independent of renal function and blood pressure (BP).
      Moreover, MI induced in renin and angiotensinogen double-transgenic (Tg) mice
      showed comparable effects to MI plus NTX mice, including advanced ventricular
      remodeling and enhancement of RAS, oxidative stress, and monocytes
      chemoattractant protein (MCP)-1. Aliskiren suppressed these changes in the MI
      induced Tg mice. In in vitro study, Nox2 expression was elevated by the
      stimulation of plasma from NTX mice in isolated neonatal cardiomyocytes. However,
      Nox2 upregulation was negated when we administered plasma from aliskiren-treated
      NTX mice or isolated cardiomyocytes from AT1-deficient mice. Primary mononuclear
      cells also showed an upregulation in the expression of Nox2 and MCP-1 by
      stimulation with plasma from NTX mice. Our data suggest that renal disorder
      results in ventricular dysfunction and deteriorates remodeling after MI through
      excessive RAS activation. Moreover, renin inhibition improved the changes caused
      by cardiorenal syndrome.

PMID- 22986787
TI  - Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates
      contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway.
AB  - The contraction of hepatic stellate cells (HSCs) has a critical role in the
      regulation of intrahepatic vascular resistance and portal hypertension. Previous
      studies have confirmed that salvianolic acid B (Sal B) is effective against liver
      fibrosis. In the present study, we evaluated the effect of Sal B on portal
      hypertension and on HSCs contractility. Liver cirrhosis was induced in rats by
      peritoneal injection of dimethylnitrosamine and the portal pressure was measured.
      HSCs contraction was evaluated by collagen gel contraction assay. Glycerol-urea
      gel electrophoresis was performed to determine the phosphorylation of myosin
      light chain 2 (MLC2). F-actin stress fiber polymerization was detected by
      fluorescein isothiocyanate-labeled phalloidin. Intracellular Ca(2+) and RhoA
      signaling activation were also measured. Sal B effectively reduced the portal
      pressure in DMN-induced cirrhotic rats. It decreased the contraction by
      endothelin-1 (ET-1)-activated HSCs by ~66.5% and caused the disassembly of actin
      stress fibers and MLC2 dephosphorylation. Although Sal B reduced ET-1-induced
      intracellular Ca(2+) increase, blocking Ca(2+) increase completely by BAPTA-AM, a
      Ca(2+) chelator, barely affected the magnitude of contraction. Sal B decreased ET
      1-induced RhoA and Rho-associated coiled coil-forming protein kinase (ROCK) II
      activation by 66.84% and by 76.79%, respectively, and inhibited Thr(696)
      phosphorylation of MYPT1 by 80.09%. In vivo, Sal B lowers the portal pressure in
      rats with DMN-induced cirrhosis. In vitro, Sal B attenuates ET-1-induced HSCs
      contraction by inhibiting the activation of RhoA and ROCK II and the downstream
      MYPT1 phosphorylation at Thr(696). We consider Sal B a potential candidate for
      the pharmacological treatment of portal hypertension.

PMID- 22986788
TI  - Endometrial stromal sarcoma arising from endometriosis: a clinicopathological
      study and literature review.
AB  - OBJECTIVES: We aimed to investigate the nature of endometrial stromal sarcoma
      (ESS) arising from endometriosis. METHODS: The clinical data of 5 patients with
      ESS arising from endometriosis were reviewed retrospectively. The expression of
      CD117, HER2/neu, EGFR, VEGF, and PDGFR was analyzed by immunohistochemical
      staining. RESULTS: The median age of the 5 patients was 45 years. The primary
      tumor sites were the ovary in 2, the pelvis in 2, and the cervical canal in 1
      patient. Three patients had disseminated disease at diagnosis. Four patients
      underwent complete tumor resection. All of the 5 cases received adjuvant
      chemotherapy and 2 received progesterone therapy, while none were treated with
      radiotherapy. No recurrence occurred in the 4 cases who had complete tumor
      resection, and the only patient who progressed was the patient in whom the tumor
      was unresectable. Tumor cells in all cases exhibited positive staining for PDGFR
      and were negative for CD117 and HER2/neu. The expression of EGFR and VEGF was
      observed in 2 and 4 cases, respectively. CONCLUSION: ESS arising from
      endometriosis is rare. Complete tumor resection in ESS arising from endometriosis
      may reduce the recurrence rate.

PMID- 22986789
TI  - The salicylic acid receptor NPR3 is a negative regulator of the transcriptional
      defense response during early flower development in Arabidopsis.
AB  - Arabidopsis non-expressor of PR1 (NPR1) is a transcription co-activator that
      plays a central role in regulating the transcriptional response to plant
      pathogens. The NPR family consists of NPR1 and five NPR1-like genes. The NPR1
      paralog NPR3 has recently been shown to function as a receptor of the plant
      hormone salicylic acid and to mediate proteosomal degradation of NPR1. The
      function of NPR3 protein during early flower development was revealed through a
      detailed molecular-genetic analysis including promoter transcriptional fusion
      analysis, phenotype characterization of npr3-3 mutants/overexpressors, and whole
      plant fitness analysis. The physical interaction between NPR3 and NPR1/TGA2 was
      explored using bimolecular fluorescence complementation analysis in onion
      epidermal cells. Here, we show that NPR3 expression was strongest in the petals
      and sepals of developing flowers and declined after flower opening. Consistently
      with this observation, an npr3 knockout mutant displayed enhanced resistance to
      Pseudomonas syringae infection of immature flowers, but not leaves. Developing
      npr3 flowers exhibited increased levels of basal and induced PR1 transcript
      accumulation. However, the npr3 mutant showed lower fitness compared to Col-0 in
      the absence of pathogen. Moreover, NPR3 was shown to interact with NPR1 and TGA2
      in vivo. Our data suggest that NPR3 is a negative regulator of defense responses
      during early flower development and it may function through the association with
      both NPR1 and TGA2.

PMID- 22986791
TI  - Two-step processing of AtFtsH4 precursor by mitochondrial processing peptidase in
      Arabidopsis thaliana.

PMID- 22986790
TI  - Overexpression of Arabidopsis YUCCA6 in potato results in high-auxin
      developmental phenotypes and enhanced resistance to water deficit.
AB  - Indole-3-acetic acid (IAA), a major plant auxin, is produced in both tryptophan
      dependent and tryptophan-independent pathways. A major pathway in Arabidopsis
      thaliana generates IAA in two reactions from tryptophan. Step one converts
      tryptophan to indole-3-pyruvic acid (IPA) by tryptophan aminotransferases
      followed by a rate-limiting step converting IPA to IAA catalyzed by YUCCA
      proteins. We identified eight putative StYUC (Solanum tuberosum YUCCA) genes
      whose deduced amino acid sequences share 50%-70% identity with those of
      Arabidopsis YUCCA proteins. All include canonical, conserved YUCCA sequences:
      FATGY motif, FMO signature sequence, and FAD-binding and NADP-binding sequences.
      In addition, five genes were found with ~50% amino acid sequence identity to
      Arabidopsis tryptophan aminotransferases. Transgenic potato (Solanum tuberosum
      cv. Jowon) constitutively overexpressing Arabidopsis AtYUC6 displayed high-auxin
      phenotypes such as narrow downward-curled leaves, increased height, erect
      stature, and longevity. Transgenic potato plants overexpressing AtYUC6 showed
      enhanced drought tolerance based on reduced water loss. The phenotype was
      correlated with reduced levels of reactive oxygen species in leaves. The results
      suggest a functional YUCCA pathway of auxin biosynthesis in potato that may be
      exploited to alter plant responses to the environment.

PMID- 22986793
TI  - What's new in Shock? October 2012.

PMID- 22986792
TI  - A global identification and analysis of small nucleolar RNAs and possible
      intermediate-sized non-coding RNAs in Oryza sativa.
AB  - Accumulating evidence suggests that non-coding RNAs (ncRNAs) are both widespread
      and functionally important in many eukaryotic organisms. In this study, we
      employed a special size fractionation and cDNA library construction method
      followed by 454 deep sequencing to systematically profile rice intermediate-size
      ncRNAs. Our analysis resulted in the identification of 1349 ncRNAs in total,
      including 754 novel ncRNAs of an unknown functional category. Chromosome
      distribution of all identified ncRNAs showed no strand bias, and displayed a
      pattern similar to that observed in protein-coding genes with few chromosome
      dependencies. More than half of the ncRNAs were centered around the plus-strand
      of the 5' and 3' termini of the coding regions. The majority of the novel ncRNAs
      were rice specific, while 78% of the small nucleolar RNAs (snoRNAs) were
      conserved. Tandem duplication drove the expansion of over half of the snoRNA gene
      families. Furthermore, 90% of the snoRNA candidates were shown to produce small
      RNAs between 20-30 nt, 80% of which were associated with ARGONAUT proteins
      generally, and AGO1b in particular. Overall, our findings provide a comprehensive
      view of an intermediate-size non-coding transcriptome in a monocot species, which
      will serve as a useful platform for an in-depth analysis of ncRNA functions.

PMID- 22986794
TI  - Effect of hydrogen gas on the survival rate of mice following global cerebral
      ischemia (Shock 37(6), 645-652, 2012).

PMID- 22986796
TI  - Outcome measures in dermatology: comment on "measurement properties of outcome
      measures for vitiligo".

PMID- 22986797
TI  - Co-occurring psychotic and addictive disorders:  neurobiology and diagnosis.
AB  - Psychosis and substance abuse are intimately related. Psychotic spectrum
      illnesses commonly co-occur with substance use disorders (SUDs), and many
      substances of abuse can cause or exacerbate psychotic symptoms along a temporal
      spectrum from acute to chronic presentations. Despite the common co-occurrence
      between psychotic spectrum illnesses and SUDs, they are often under-recognized
      and undertreated, leading to poor treatment outcomes. Accurate detection and
      diagnosis of individuals with psychotic illness co-occurring with addictive
      disorders is key to properly treat such disorders. This article will review the
      nature of the relationship between psychosis and substance abuse by examining
      prevalence rates of each disorder alone and their rates of co-occurrence, the
      neurobiological basis for substance abuse comorbidity in schizophrenia spectrum
      disorders, key and salient aspects related to accurate diagnosis along a
      continuum from acute to subacute to chronic conditions, and pitfalls associated
      with diagnostic dilemmas. A case example will be used to highlight key points
      related to diagnostic challenges.

PMID- 22986798
TI  - Antipsychotics and abnormal liver function tests:  systematic review.
AB  - OBJECTIVE: Systematic assessment of the prevalence and pattern of liver function
      test (LFT) abnormalities associated with regular antipsychotics in adult humans
      and consideration of management of such abnormalities. DATA SOURCES: Systematic
      search identifying cohort, cross-sectional or case studies/series, reporting LFT
      abnormalities in patients receiving regular antipsychotics. EMBASE, PsychINFO,
      and MEDLINE were searched for studies in English from record onset. STUDY
      SELECTION: Abstracts were independently screened for eligibility by 2
      researchers. Ineligible studies included those that did not report LFT reference
      ranges, those that studied fewer than 10 patients on a given antipsychotic, and
      those studying children. DATA EXTRACTION: Key variables in group studies were
      extracted. Case studies/series were examined for patient outcome. DATA SYNTHESIS:
      Ten group studies and 91 case studies/series were eligible, although quality was
      poor. All groups receiving regular antipsychotics had a prevalence of LFT
      abnormalities greater than chance. The median percentage of patients with any
      abnormal LFT on any antipsychotic was 32%, with a range of 5% to 78%. The median
      percentage of patients with clinically significant elevations was 4%, with a
      range of 0% to 15%. Transaminases were most commonly elevated. Abnormalities were
      generally asymptomatic, arose within 6 weeks, and were either stably persistent
      or resolved with continued treatment. Case reports suggested that antipsychotics
      can be associated with severe hepatitis, fatal in a small minority of cases.
      Chlorpromazine is most commonly associated with acute liver injury. CONCLUSIONS:
      The LFT abnormalities in patients receiving regular antipsychotics are common but
      generally mild and transient. Very rarely, a severe or fatal hepatic injury can
      emerge.

PMID- 22986799
TI  - Iatrogenic botulism after the therapeutic use of botulinum toxin-A: a case report
      and review of the literature.
AB  - Local injection of botulinum toxin-A is an accepted treatment for hyperhidrosis.
      We report 2 cases of primary hyperhidrosis who developed iatrogenic botulism
      after the therapeutic dose of onabotulinumtoxinA (Botox). This case report
      highlights the necessity of clinicians having sufficient information of
      potentially adverse effects, optimal dose, and correct preparation and injection
      of botulinum toxin-A.

PMID- 22986800
TI  - Relief of intractable posthypoxic myoclonus after administration of agomelatine.
AB  - Chronic posthypoxic myoclonus is characterized by myoclonic jerks that are
      specifically triggered by action. It is a rare but devastating sequela of hypoxic
      encephalopathy. We report a 42-year-old female patient with treatment-resistant
      chronic posthypoxic myoclonus, which improved with administration of the drug
      agomelatine. We suggest that agomelatine could represent a useful therapeutic
      option in the treatment of chronic posthypoxic myoclonus.

PMID- 22986801
TI  - Toxicology fellow's perspective: filling a void in medical education regarding
      opioids.

PMID- 22986802
TI  - Are knee and foot orthopedic problems more disabling in the superobese?
AB  - BACKGROUND: Aiming to ascertain whether frequency and severity of knee and foot
      problems were different between morbid obesity (MO) and superobesity (SO), a
      prospective clinical study was designed. METHODS: Bariatric candidates (N = 81,
      body mass index 40-81.3 kg/m(2), 43.2 % with SO) were submitted to knee and foot
      radiologic assessment, baropodometric footprint measurement, and the
      questionnaires Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) and Foot and Ankle Outcome Score (FAOS). Main outcome measures were
      imaging diagnosis of knee osteoarthritis and flatfoot, along with functional
      impact on activities of daily living estimated by the questionnaires. RESULTS:
      Knee osteoarthritis was radiologically diagnosed in 74.1 % (60/81), and the
      entire cohort suffered from flatfoot according to both footprint index and talar
      first metatarsal radiographic angle; nevertheless, distribution was not different
      between SO and MO. However, WOMAC and FAOS scores were markedly worse in SO,
      affecting joint pain, stiffness, and general mobility. This is the first protocol
      of our knowledge to address foot and knee derangements in SO. CONCLUSIONS:
      Functional impairment was more severe in SO, despite a morphologic pattern
      similar to MO. Even though amelioration is probable with weight loss, long-term
      orthopedic assistance might be required in such circumstances.

PMID- 22986803
TI  - Intrasilicone bevacizumab injection for iris neovascularization after vitrectomy
      for proliferative diabetic retinopathy.
AB  - PURPOSE: To evaluate the efficacy and safety of intrasilicone injection of
      bevacizumab for the treatment of iris neovascularization after vitrectomy for
      proliferative diabetic retinopathy. METHODS: Bevacizumab 1.25 mg/0.05 ml was
      injected into silicone oil in 15 eyes of 11 patients with iris neovascularization
      which had developed 2.5-6 months after vitrectomy and silicone oil tamponade. The
      main outcome measures were regression of iris neovascularization, intraocular
      pressure elevation, and visual acuity. RESULTS: In all eyes, iris
      neovascularization regressed and postinjection intraocular pressure was
      controlled within 7 days postinjection. Visual acuity improved in 12 eyes. In 4
      patients, iris neovascularization recurred within 10 weeks after the injection
      and they were successfully treated with a second intrasilicone bevacizumab
      injection of the same dose. CONCLUSION: Intrasilicone injection of bevacizumab is
      safe and effective in the treatment of patients with iris neovascularization
      after vitrectomy for advanced proliferative diabetic retinopathy. Further studies
      on greater numbers of patients and more advanced neovascularization are
      recommended.

PMID- 22986804
TI  - Validation of continuous and noninvasive hemoglobin monitoring by pulse CO
      oximetry in Japanese surgical patients.
AB  - We evaluated the accuracy of noninvasive and continuous total hemoglobin (SpHb)
      monitoring with the Radical-7((r)) Pulse CO-Oximeter in Japanese surgical
      patients before and after an in vivo adjustment of the first SpHb value to match
      the first reference value from a satellite laboratory CO-Oximeter. Twenty
      patients undergoing surgical procedures with general anesthesia were monitored
      with Pulse CO-Oximetry for SpHb. Laboratory CO-Oximeter values (tHb) were
      compared to SpHb at the time of the blood draws. Bias, precision, limits of
      agreement and correlation coefficient of SpHb compared to tHb were calculated
      before and after SpHb values were adjusted by subtracting the difference between
      the first SpHb and tHb value from all subsequent SpHb values. Trending of SpHb to
      tHb and the effect of perfusion index (PI) on the agreement of SpHb to tHb were
      also analyzed. Ninety-two tHb values were compared to the SpHb. Bias +/- 1SD was
      0.2 +/- 1.5 g/dL before in vivo adjustment and -0.7 +/- 1.0 g/dL after in vivo
      adjustment. Bland-Altman analysis showed limits of agreement of -2.8 to 3.1 g/dL
      before in vivo adjustment and -2.8 to 1.4 g/dL after in vivo adjustment. The
      correlation coefficient was 0.76 prior to in vivo adjustment and 0.87 after in
      vivo adjustment. In patients with adequate perfusion (PI >=1.4) the correlation
      coefficient was 0.89. In vivo adjustment of SpHb significantly improved the
      accuracy in our cohort of Japanese surgical patients. The strongest correlation
      between SpHb and tHb values was observed in patients with adequate peripheral
      perfusion suggesting that low perfusion may affect the accuracy of SpHb
      monitoring.

PMID- 22986805
TI  - Quantum confinement effect of CdSe induced by nanoscale solvothermal reaction.
AB  - We report a novel method, nanoscale solvothermal reaction (NSR), to induce the
      quantum confinement effect of CdSe on nanostructured TiO(2) by solvothermal
      route. The time-dependent growth of CdSe is observed in solution at room
      temperature, which is found to be accomplished instantly by heat-treatment in the
      presence of solvent at 1 atm. However, no crystal growth occurs upon heat
      treatment in the absence of solvent. The nanoscale solvothermal growth of CdSe
      quantum dot is realized on the nanocrystalline oxide surface, where
      Cd(NO(3))(2).4H(2)O and Na(2)SeSO(3) solutions are sequentially spun on
      nanostructured TiO(2), followed by heat-treatment at temperatures ranging from
      100  degrees C to 250  degrees C. Size of CdSe increases from 4.4 nm to 5.3 nm,
      8.7 nm and 14.8 nm, which results in decrease in optical band gap from 2.19 eV
      to, 1.95 eV, 1.74 eV and 1.75 eV with increasing the NSR temperature from 100 
      degrees C to 150  degrees C, 200  degrees C and 250  degrees C, respectively,
      which is indicative of the quantum confinement effect. Thermodynamic studies
      reveal that increase in the size of CdSe is related to increase in enthalpy, for
      instance, from 3.77 J mg(-1) for 100  degrees C to 8.66 J mg(-1) for 200  degrees
      C. Quantum confinement effect is further confirmed from the CdSe-sensitized solar
      cell, where onset wavelength in external quantum efficiency spectra is
      progressively shifted from 600 nm to 800 nm as the NSR temperature increases,
      which leads to a significant improvement of power conversion efficiency by a
      factor of more than four. A high photocurrent density of 13.7 mA cm(-2) is
      obtained based on CdSe quantum dot grown by NSR at 200  degrees C.

PMID- 22986806
TI  - Exploring doxorubicin localization in eluting TiO2 nanotube arrays through
      fluorescence correlation spectroscopy analysis.
AB  - Drug elution properties of TiO(2) nanotube arrays have been largely investigated
      by means of solely macroscopic observations. Controversial elution performances
      have been reported so far and a clear comprehension of these phenomena is still
      missing as a consequence of a lack of molecular investigation methods. Here we
      propose a way to discern drug elution properties of nanotubes through the
      evaluation of drug localization by Fluorescence Correlation Spectroscopy (FCS)
      analysis. We verified this method upon doxorubicin elution from differently
      loaded TiO(2) nanotubes. Diverse elution profiles were obtained from nanotubes
      filled by soaking and wet vacuum impregnation methods. Impregnated nanotubes
      controlled drug diffusion up to thirty days, while soaked samples completed
      elution in seven days. FCS analysis of doxorubicin motion in loaded nanotubes
      clarified that more than 90% of drugs dwell preferentially in inter-nanotube
      spaces in soaked samples due to decorrelation in a 2D fashion, while a 97%
      fraction of molecules showed 1D mobility ascribable to displacements along the
      nanotube vertical axis of wet vacuum impregnated nanotubes. The diverse drug
      localizations inferred from FCS measurements, together with distinct drug-surface
      interaction strengths resulting from diverse drug filling techniques, could
      explain the variability in elution kinetics.

PMID- 22986807
TI  - On the interplay between charge, spin and structural dynamics in transition metal
      complexes.
AB  - This perspective presents some recent results concerning ultrafast intramolecular
      relaxation processes in metal-based molecular complexes. Ultrafast
      electronic/vibrational relaxation at sub-vibrational time scales, ultrafast
      intersystem crossing processes and ultrafast structure changes are discussed,
      stressing the questions that still need to be solved in order to arrive at a
      rationale that describes these processes. We will also discuss some new
      techniques, based on core-level spectroscopies that can provide new insights into
      the ultrafast intramolecular relaxation in these systems.

PMID- 22986808
TI  - Tripeptidyl peptidase II in human oral squamous cell carcinoma.
AB  - PURPOSE: Tripeptidyl peptidase II (TPP2), a member of the family of eukaryotic
      serine peptidase, has been implicated in DNA repair, cellular division, and
      apoptosis. The aim of this study was to examine TPP2 expression and its
      functional mechanisms in oral squamous cell carcinoma (OSCC). METHODS: TPP2 mRNA
      and protein expression in seven OSCC-derived cells (Ca9-22, HSC-2, HSC-3, HSC-4,
      HO-1-N-1, H1, and Sa3) was analyzed by quantitative reverse transcriptase
      polymerase chain reaction and immunoblotting analyses. Since previous studies
      indicated that TPP2 might control chromosomal division, we investigated cellular
      proliferation and spindle assembly checkpoint (SAC) molecules, MAD2 and CCNB1. In
      addition, we evaluated the correlation between TPP2 expression levels in primary
      OSCCs (n = 108 specimens) and the clinicopathologic status by
      immunohistochemistry (IHC). RESULTS: TPP2 mRNA and protein were significantly (P
      < 0.05) up-regulated in OSCC-derived cells compared with human normal oral
      keratinocytes. Suppression of TPP2 expression with shRNA significantly (P < 0.05)
      inhibited cellular proliferation compared with the control cells. In addition,
      appropriate localization of MAD2 and up-regulation of CCNB1 were observed in TPP2
      knockdown OSCC cells. IHC showed that TPP2 expression in primary OSCCs was
      significantly (P < 0.001) greater than that in the normal oral counterparts, and
      the TPP2-positive cases were significantly (P < 0.05) correlated with tumor size.
      CONCLUSION: The current study showed that overexpression of TPP2 occurs
      frequently during oral carcinogenesis and might be associated with OSCC
      progression via SAC activation.

PMID- 22986809
TI  - Significant correlation between LKB1 and LGR5 gene expression and the association
      with poor recurrence-free survival in rectal cancer after preoperative
      chemoradiotherapy.
AB  - PURPOSE: The aim of the present study was to investigate whether the gene
      expression levels of LKB1 and LGR5 correlated with clinical outcome in patients
      with locally advanced rectal cancer treated with preoperative chemoradiotherapy
      (CRT). METHODS: Residual cancer cells were obtained from 52 patients with locally
      advanced rectal cancer treated with preoperative CRT. Total RNA was then isolated
      from formalin-fixed, paraffin-embedded specimens using microdissection. The
      expression levels of LKB1 and LGR5 genes were measured using real-time reverse
      transcription polymerase chain reaction and by immunohistochemistry. In addition,
      in vitro studies were performed using colon cancer cell lines to study the serial
      changes of LKB1, LGR5 and PRKAA1 (AMPK) gene expression levels after irradiation.
      RESULTS: Our data demonstrate that specimens obtained from patients with poor
      pathological response and tumor recurrence had significantly higher gene
      expression levels of LKB1 and LGR5 than those without them (P < 0.05), and there
      was a significant positive correlation between LKB1 and LGR5 gene expression
      after CRT (Spearman's rho: 0.429, P = 0.0023). The patients with high expression
      levels of both LKB1 and LGR5 had a significantly lower recurrence-free survival
      compared with the other group (P = 0.0055, 95 % confidence interval: 1.39-11.08).
      Lastly, in vitro studies demonstrated a similar pattern of serial gene expression
      among LKB1, LGR5 and PRKAA1 after irradiation. CONCLUSIONS: Our results suggest
      that LKB1 and LGR5 expression may be implicated in resistance to CRT, therefore
      contributing to tumor relapse in patients with locally advanced rectal cancer
      treated with preoperative CRT.

PMID- 22986810
TI  - Adjuvant and salvage radiotherapy after prostatectomy: outcome analysis of 307
      patients with prostate cancer.
AB  - AIM: In men with adverse pathology after radical prostatectomy, the most
      appropriate timing to administer radiotherapy (RT) remains a topic of debate. We
      analyzed in terms of efficacy, prognostic factors and toxicity the two
      therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage
      radiotherapy (SART). MATERIALS AND METHODS: Between January 1995 and November
      2010, 307 patients underwent adjuvant or salvage radiotherapy, after
      prostatectomy. RESULTS: In the PORT group, 42 patients (20.7 %) had biochemical
      failure, with a median time to biochemical failure of 1.8 years; two parameters
      (age at diagnosis and PSA pre-RT) resulted to be significant at the survival
      analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the
      SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died
      of prostate cancer; postoperative hormones therapy, conformal radiotherapy and
      level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival
      analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. CONCLUSION: Our study
      is limited by its retrospective and nonrandomized design. As such, decisions to
      treat with adjuvant or salvage radiotherapy and the time to initiate therapy were
      based on patient preference and physician counseling. Our recommendation is to
      suggest adjuvant radiotherapy for all patients with adverse prognostic factors
      and to reserve salvage radiotherapy for low-risk patients, when the biochemical
      recurrence occurs.

PMID- 22986811
TI  - MGMT testing for glioma in clinical laboratories: discordance with methylation
      analyses prevents the implementation of routine immunohistochemistry.
AB  - PURPOSE: Glioblastoma is a universally fatal cancer of the central nervous system
      which responds poorly to treatment. MGMT has potential as a predictive biomarker
      in glioblastoma patients to determine treatment response. However, methods of
      measuring MGMT are currently unsatisfactory, and as such, use of this marker has
      not translated well into the clinic. This paper aims to review current
      methodology of MGMT measurement, with a focus on immunohistochemistry as a
      potential way forward. TOPICS AND METHODS: Studies of glioma patients where MGMT
      immunohistochemistry was undertaken, as well as the literature surrounding
      methylation analyses and the regulation of MGMT, were reviewed. RESULTS: All
      methods of measuring MGMT were disputed in some way in the literature. A trend of
      discordance between methylation analyses and protein analyses was present. There
      is a lack of standardisation in the measurement of MGMT, and as a result, it
      seems that there are highly variable results. CONCLUSIONS: No single method of
      MGMT analysis has emerged as a clear choice for routine clinical testing of MGMT
      in glioma patients. Although methylation analyses are favoured, their expense and
      inaccessibility are barriers to their use in routine clinical practice. More
      research into immunohistochemistry is needed to determine whether it can serve as
      a reliable and cost-effective alternative to methylation analyses.

PMID- 22986812
TI  - Definitive intensity-modulated radiation therapy for nasopharyngeal carcinoma:
      long-term outcome of a multicenter prospective study.
AB  - PURPOSE: To evaluate long-term outcome in nasopharyngeal carcinoma (NPC) treated
      with intensity-modulated radiation therapy. METHODS: Between January 2006 and
      August 2008, 300 patients with histologically proven NPC were enrolled in this
      multicenter prospective study. All patients received definitive IMRT. Cisplatin
      based concurrent chemotherapy was given to patients with stages III-IVb disease.
      RESULTS: Median follow-up time was 47.1 months (range 11-68 months). Median
      survival time was not reached. For all patients, the 4-year local control (LC),
      regional control (RC), distant metastasis-free survival (DMFS), and overall
      survival (OS) were 94.0, 95.1, 85.0, and 86.1 %, respectively. Thirty-five
      patients experienced locoregional failures: 18 were local only, 15 were regional
      only, and 2 were both local and regional. Forty-two patients developed distant
      metastasis. Of these, 32 patients had single organ metastasis, and 10 patients
      had multiple organ metastasis. The most common acute toxicities were mucositis,
      dermatitis, and xerostomia. Grade 0-2 mucositis, dermatitis, and xerostomia
      occurred in 200 patients (66.7 %), 288 patients (96.0 %), and 286 patients (95.3
      %), respectively. Grade 3 mucositis, dermatitis, and xerostomia were seen in 100
      patients (33.3 %), 12 patients (4.0 %), and 14 patients (4.7 %), respectively. No
      Grade 4 acute toxicities were observed. The most common late toxicity for 284
      patients who survived for more than 2 years was xerostomia. At 3 months after
      treatment, 16.2 % of patients had Grade 1, 73.6 % had Grade 2, and 10.2 % had
      Grade 3 xerostomia. However, the severity of xerostomia decreased over time. At
      24 months, only 12.3 % of patients had Grade 2 xerostomia, and none had Grade 3
      or 4 xerostomia. CONCLUSIONS: IMRT for NPC patients achieved excellent long-term
      locoregional control (LRC) and OS, with acceptable acute and late toxicities.
      After the treatment, xerostomia was improved over time. Distant metastasis
      remained the main cause of failure. More effective systemic therapy is demanding
      for reducing the risk of distant metastasis.

PMID- 22986813
TI  - Potential implications of adjuvant endocrine therapy for the oral health of
      postmenopausal women with breast cancer.
AB  - Current adjuvant treatment modalities for breast cancer that express the estrogen
      receptor or progesterone receptor include adjuvant anti-estrogen therapies, and
      tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine
      sensitive organ, as are other oral structures. This review examines the potential
      links between adjuvant anti-estrogen treatments in postmenopausal women with
      hormone receptor positive breast cancer and oral health. A search of PubMed,
      EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key
      terms "breast," "cancer," "neoplasm," "Tamoxifen," "Aromatase Inhibitor,"
      "chemotherapy," "hormone therapy," "alveolar bone loss," "postmenopausal bone
      loss," "estrogen," "SERM," "hormone replacement therapy," and "quality of life."
      We selected articles published in peer-reviewed journals in the English. The
      authors found no studies reporting on periodontal diseases, alveolar bone loss,
      oral health, or oral health-related quality of life in association with anti
      estrogen breast cancer treatments in postmenopausal women. Periodontal diseases,
      alveolar bone density, tooth loss, and conditions of the soft tissues of the
      mouth have all been associated with menopausal status supporting the hypothesis
      that the soft tissues and bone of the oral cavity could be negatively affected by
      anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast
      cancer therapy on the oral health of postmenopausal women is undefined. The
      structures of the oral cavity are influenced by estrogen; therefore, anti
      estrogen therapies may carry the risk of oral toxicities. Oral health care for
      breast cancer patients is an important but understudied aspect of cancer
      survivorship.

PMID- 22986814
TI  - Intratumoral regulatory T cells as an independent predictive factor for
      pathological complete response to neoadjuvant paclitaxel followed by 5
      FU/epirubicin/cyclophosphamide in breast cancer patients.
AB  - Anti-tumor immunity is thought to play a significant role in chemotherapeutic
      response of breast tumors. In the present study, we investigated whether tumor
      infiltrating FOXP3+ regulatory T cells, CD8+ cytotoxic T cells, and IL17F+ helper
      T cells were associated with a pathological complete response (pCR) to
      neoadjuvant chemotherapy (NAC). Breast cancer patients (stages II and III, n =
      180) who were treated with NAC consisting of sequential weekly paclitaxel
      followed by 5-FU/epirubicin/cyclophosphamide were included for this study. Core
      needle tumor specimens obtained before NAC were immunohistochemically examined
      for FOXP3, CD8, and IL17F. Intratumoral infiltration of FOXP3+, CD8+, and IL17F+
      T cells was observed in 62.2, 80.0, and 62.2 % of tumors, respectively. FOXP3 and
      CD8 infiltrates, but not IL17F infiltrate, were significantly (P < 0.001 and P =
      0.007, respectively) associated with a high-pCR rate (31.3 and 25.7 %,
      respectively), and breast tumors with both FOXP3 and CD8 infiltrates showed the
      highest pCR rate (33.0 %). Multivariate analysis indicated that only FOXP3
      infiltrates (P = 0.014) and the conventional predictive factor Ki67 (P = 0.031)
      were statistically significant and independent predictors of pCR. Breast tumors
      with FOXP3 and CD8 infiltrates were more likely to achieve pCR. FOXP3 infiltrate,
      in combination with Ki67, could thus be used as a clinically useful predictor of
      response to NAC. The possible indirect mechanism through which chemotherapy
      exerts its anti-tumor activity, i.e., enhancing anti-tumor immunity by inhibiting
      FOXP3, was also suggested.

PMID- 22986815
TI  - A model of proteolysis and amino acid biosynthesis for Lactobacillus delbrueckii
      subsp. bulgaricus in whey.
AB  - Lactobacillus delbrueckii subsp. bulgaricus 2038 (L. bulgaricus 2038) is a
      bacterium that is used as a starter for dairy products by Meiji Co., Ltd of
      Japan. Culturing L. bulgaricus 2038 with whey as the sole nitrogen source results
      in a shorter lag phase than other milk proteins under the same conditions (carbon
      source, minerals, and vitamins). Microarray results of gene expression revealed
      characteristics of amino acid anabolism with whey as the nitrogen source and
      established a model of proteolysis and amino acid biosynthesis for L. bulgaricus.
      Whey peptides and free amino acids are readily metabolized, enabling rapid entry
      into the logarithmic growth phase. The oligopeptide transport system is the
      primary pathway for obtaining amino acids. Amino acid biosynthesis maintains the
      balance between amino acids required for cell growth and the amount obtained from
      environment. The interconversion of amino acids is also important for L.
      bulgaricus 2038 growth.

PMID- 22986816
TI  - Biotransformation of ferulic acid to 4-vinylguaiacol by Enterobacter soli and E.
      aerogenes.
AB  - We investigated the conversion of ferulic acid to 4-vinylguaiacol (4-VG),
      vanillin, vanillyl alcohol, and vanillic acid by five Enterobacter strains. These
      high-value chemicals are usually synthesized by chemical methods but biological
      synthesis adds market value. Ferulic acid, a relatively inexpensive component of
      agricultural crops, is plentiful in corn hulls, cereal bran, and sugar-beet pulp.
      Two Enterobacter strains, E. soli, and E. aerogenes, accumulated 550-600 ppm
      amounts of 4-VG when grown in media containing 1,000 ppm ferulic acid; no
      accumulations were observed with the other strains. Decreasing the amount of
      ferulic acid present in the media increased the conversion efficiency. When
      ferulic acid was supplied in 500, 250, or 125 ppm amounts E. aerogenes converted
      ~72 % of the ferulic acid present to 4-VG while E. soli converted ~100 % of the
      ferulic acid to 4-VG when supplied with 250 or 125 ppm amounts of ferulic acid.
      Also, lowering the pH improved the conversion efficiency. At pH 5.0 E. aerogenes
      converted ~84 % and E. soli converted ~100 % of 1,000 ppm ferulic acid to 4-VG.
      Only small, 1-5 ppm, accumulations of vanillin, vanillyl alcohol, and vanillic
      acid were observed. E. soli has a putative phenolic acid decarboxylase (PAD) that
      is 168 amino acids long and is similar to PADs in other enterobacteriales; this
      protein is likely involved in the bioconversion of ferulic acid to 4-VG. E. soli
      or E. aerogenes might be useful as a means of biotransforming ferulic acid to 4
      VG.

PMID- 22986817
TI  - AiiA quorum-sensing quenching controls proteolytic activity and biofilm formation
      by Enterobacter cloacae.
AB  - The aim of this work was to evaluate a quorum-quenching approach to identify
      functions regulated by quorum sensing in Enterobacter cloacae. We employed an
      aiiA transconjugant strain of E. cloacae that synthesizes a lactonase enzyme that
      hydrolyzes N-acyl homoserine lactone signaling molecules to compare bacterial
      phenotypes in the presence and absence of quorum signals. The aiiA-expressing
      strain displayed increased proteolytic activity and intensity of a milk-clotting
      reaction when compared to the wild-type strain. Although both strains growing on
      polystyrene plates in rich media and a minimal medium of salts formed biofilms,
      the wild-type strain exhibited a higher number of adhered cells. On the surface
      of stainless steel coupons that were submerged in culture media, the number of
      adhered cells of the wild type contained up to one log more cells compared with
      the aiiA transconjugant. However, after 48 h of incubation, there was no
      significant difference between the strains. The results demonstrated that the
      quorum-sensing system negatively regulates proteolytic activity and is likely
      involved in the early steps of biofilm formation by E. cloacae 067.

PMID- 22986818
TI  - D-amino acid-induced expression of D-amino acid oxidase in the yeast
      Schizosaccharomyces pombe.
AB  - We investigated D-amino acid oxidase (DAO) induction in the popular model yeast
      Schizosaccharomyces pombe. The product of the putative DAO gene of the yeast
      expressed in E. coli displayed oxidase activity to neutral and basic D-amino
      acids, but not to an L-amino acid or acidic D-amino acids, showing that the
      putative DAO gene encodes catalytically active DAO. DAO activity was weakly
      detected in yeast cells grown on a culture medium without D-amino acid, and was
      approximately doubled by adding D-alanine. The elimination of ammonium chloride
      from culture medium induced activity by up to eight-fold. L-Alanine also induced
      the activity, but only by about half of that induced by D-alanine. The induction
      by D-alanine reached a maximum level at 2 h cultivation; it remained roughly
      constant until cell growth reached a stationary phase. The best inducer was D
      alanine, followed by D-proline and then D-serine. Not effective were N-carbamoyl
      D,L-alanine (a better inducer of DAO than D-alanine in the yeast Trigonopsis
      variabilis), and both basic and acidic D-amino acids. These results showed that
      S. pombe DAO could be a suitable model for analyzing the regulation of DAO
      expression in eukaryotic organisms.

PMID- 22986819
TI  - Evidence for two promoters internal to the alginate biosynthesis operon in
      Pseudomonas aeruginosa.
AB  - While much is known about the transcriptional regulation of the 12 gene alginate
      biosynthesis operon from the algD promoter in Pseudomonas aeruginosa, there has
      been little investigation into the possibility of other transcription starts
      within this operon, especially those genes dealing with the epimerization and
      acetylation of the alginate polymer. In this study, we utilized quantitative
      reverse transcription polymerase chain reaction, a beta-galactosidase reporter
      assay and sequence scanning to identify two putative promoters within the
      alginate biosynthesis operon upstream of the alginate epimerase gene algG and the
      alginate acetylation gene algI. These data support the possibility of
      differential regulation within the operon to alter polymer structure under
      varying environmental conditions.

PMID- 22986820
TI  - Extracellular enzyme activity in a willow sewage treatment system.
AB  - This paper presents the results of studies on the activity of extra-cellular
      enzymes in soil-willow vegetation filter soil which is used in the post-treatment
      of household sewage in an onsite wastewater treatment system located in central
      Poland. Wastewater is discharged from the detached house by gravity into the
      onsite wastewater treatment system. It flows through a connecting pipe into a
      single-chamber septic tank and is directed by the connecting pipe to a control
      well to be further channelled in the soil-willow filter by means of a subsurface
      leaching system. Soil samples for the studies were collected from two depths of 5
      cm and 1 m from three plots: close to the wastewater inflow, at mid-length of the
      plot and close to its terminal part. Soil samples were collected from May to
      October 2009. The activity of the extra-cellular enzymes was assayed by the
      fluorometric method using 4-methylumbelliferyl and 7-amido-4-methylcoumarin
      substrate. The ranking of potential activity of the assayed enzymes was the same
      at 5 cm and 1 m soil depths, i.e. esterase > phosphmomoesterase > leucine
      aminopeptidase > beta-glucosidase > alpha-glucosidase. The highest values of
      enzymatic activity were recorded in the surface layer of the soil at the
      wastewater inflow and decreased with increasing distance from that point.

PMID- 22986821
TI  - Microbial ecology and association of Bacillus thuringiensis in chicken feces
      originating from feed.
AB  - To explain the association of Bacillus thuringiensis (Bt) with animal feces, an
      ecological analysis in chickens was conducted by introducing a cry(-) strain
      marked by production of green fluorescent protein (GFP). After feeding with the
      tagged Bt strains, the feces of the tested chickens were collected at different
      times, isolated, and the morphology of Bt was observed. It was shown that Bt
      strain HD-73GFP in spore form could be isolated from feces of chickens for a
      period of 13 d, and then it disappeared thereafter. Bt could be detected only up
      to day 4 (but not thereafter), when chickens were fed with vegetative cells of HD
      73GFP. To confirm the source of newly isolated strains, the gfp gene was examined
      by polymerase chain reaction (PCR), which showed that all the isolated strains
      harbored the marker gene. Recent data from isolation and PCR had suggested that
      fecal Bt strains had originated from food. Chicken tissues were thus dissected to
      isolate Bt strains and to investigate whether Bt could be located in vivo. Bt was
      located within the duodenum in spore form. Compared to the morphology of the
      isolated strains at different growth times, the growth rates of all the tested Bt
      had little changes when passing through the digestive system to the feces.
      Dissection of the chickens confirmed that Bt was safe for the tested animal.

PMID- 22986822
TI  - Comments on O'Brien et al.: prevalence and outcome of cirrhosis patients admitted
      to UK intensive care: a comparison against dialysis-dependent chronic renal
      failure patients.

PMID- 22986824
TI  - The nervous system of cartilaginous fishes. Preface.

PMID- 22986825
TI  - The neuroecology of cartilaginous fishes: sensory strategies for survival.
AB  - As apex predators, chondrichthyans, or cartilaginous fishes, hold an important
      position within a range of aquatic ecosystems and influence the balance between
      species' abundance and biodiversity. Having been in existence for over 400
      million years and representing the earliest stages of the evolution of jawed
      vertebrates, this group also covers a diverse range of eco-morphotypes, occupying
      both marine and freshwater habitats. The class Chondrichthyes is divided into two
      subclasses: the Elasmobranchii (sharks, skates, and rays) and the Holocephali
      (elephant sharks and chimaeras). However, many of their life history traits, such
      as low fecundity, the production of small numbers of highly precocious young,
      slow growth rates, and late maturity, make them highly susceptible to human
      exploitation. To mitigate the negative effects of human impacts, it is important
      that we understand the sensory strategies that elasmobranchs use for navigating
      within their environment, forming reproductive aggregations, feeding, and even
      communicating. One approach to investigate the sensory bases of their behavior is
      to examine the peripheral sense organs mediating vision, olfaction, gustation,
      lateral line, electroreception, and audition in a large range of species in order
      to identify specific adaptations, the range of sensitivity thresholds, and the
      compromise between sensory spatial resolution and sensitivity. In addition, we
      can quantitatively assess the convergence of sensory input to the central nervous
      system and the relative importance of different sensory modalities. Using a
      comparative approach and often a combination of anatomical, electrophysiological,
      and molecular techniques, significant variation has been identified in the
      spatial and chromatic sampling of the photoreceptors in the eye, the surface area
      and the number of olfactory lamellae within the nasal cavity, the level of
      gustatory sampling within the oral cavity, the type and innervation of neuromasts
      of the lateral line system, the distribution of electroreceptive pores over the
      head, and the morphology of the inner ear. These results are presented in the
      context of predictions of sensory capabilities for species living in a range of
      ecological niches, what further research is needed, and how this sensory input
      may be a predictor of behavior.

PMID- 22986826
TI  - Electroreception in elasmobranchs: sawfish as a case study.
AB  - The ampullae of Lorenzini are the electroreceptors of elasmobranchs. Ampullary
      pores located in the elasmobranch skin are each connected to a gel-filled canal
      that ends in an ampullary bulb, in which the sensory epithelium is located. Each
      ampulla functions as an independent receptor that measures the potential
      difference between the ampullary pore opening and the body interior. In the
      elasmobranch head, the ampullary bulbs of different ampullae are aggregated in 3
      6 bilaterally symmetric clusters, which can be surrounded by a connective tissue
      capsule. Each cluster is innervated by one branch of the anterior lateral line
      nerve (ALLN). Only the dorsal root of the ALLN carries electrosensory fibers,
      which terminate in the dorsal octavo-lateral nucleus (DON) of the medulla. Each
      ampullary cluster projects into a distinctive area in the central zone of the
      DON, where projection areas are somatotopically arranged. Sharks and rays can
      possess thousands of ampullae. Amongst other functions, the use of
      electroreception during prey localization is well documented. The distribution of
      ampullary pores in the skin of elasmobranchs is influenced by both the phylogeny
      and ecology of a species. Pores are grouped in distinct pore fields, which remain
      recognizable amongst related taxa. However, the density of pores within a pore
      field, which determines the electroreceptive resolution, is influenced by the
      ecology of a species. Here, I compare the pore counts per pore field between
      rhinobatids (shovelnose rays) and pristids (sawfish). In both groups, the number
      of ampullary pores on the ventral side of the rostrum is similar, even though the
      pristid rostrum can comprise about 20% of the total length. Ampullary pore
      numbers in pristids are increased on the upper side of the rostrum, which can be
      related to a feeding strategy that targets free-swimming prey in the water
      column. Shovelnose rays pin their prey onto the substrate with their disk, while
      repositioning their mouth for ingestion and thus possess large numbers of pores
      ventrally around the mouth and in the area between the gills.

PMID- 22986827
TI  - Allometric scaling of the optic tectum in cartilaginous fishes.
AB  - In cartilaginous fishes (Chondrichthyes; sharks, skates and rays (batoids), and
      holocephalans), the midbrain or mesencephalon can be divided into two parts, the
      dorsal tectum mesencephali or optic tectum (analogous to the superior colliculus
      of mammals) and the ventral tegmentum mesencephali. Very little is known about
      interspecific variation in the relative size and organization of the components
      of the mesencephalon in these fishes. This study examined the relative
      development of the optic tectum and the tegmentum in 75 chondrichthyan species
      representing 32 families. This study also provided a critical assessment of
      attempts to quantify the size of the optic tectum in these fishes volumetrically
      using an idealized half-ellipsoid approach (method E), by comparing this method
      to measurements of the tectum from coronal cross sections (method S). Using
      species as independent data points and phylogenetically independent contrasts,
      relationships between the two midbrain structures and both brain and
      mesencephalon volume were assessed and the relative volume of each brain area
      (expressed as phylogenetically corrected residuals) was compared among species
      with different ecological niches (as defined by primary habitat and lifestyle).
      The relatively largest tecta and tegmenta were found in pelagic coastal/oceanic
      and oceanic sharks, benthopelagic reef sharks, and benthopelagic coastal sharks.
      The smallest tecta were found in all benthic sharks and batoids and the majority
      of bathyal (deep-sea) species. These results were consistent regardless of which
      method of estimating tectum volume was used. We found a highly significant
      correlation between optic tectum volume estimates calculated using method E and
      method S. Taxon-specific variation in the difference between tectum volumes
      calculated using the two methods appears to reflect variation in both the shape
      of the optic tectum relative to an idealized half-ellipsoid and the volume of the
      ventricular cavity. Because the optic tectum is the principal termination site
      for retinofugal fibers arising from the retinal ganglion cells, the relative size
      of this brain region has been associated with an increased reliance on vision in
      other vertebrate groups, including bony fishes. The neuroecological relationships
      between the relative size of the optic tectum and primary habitat and lifestyle
      we present here for cartilaginous fishes mirror those established for bony
      fishes; we speculate that the relative size of the optic tectum and tegmentum
      similarly reflects the importance of vision and sensory processing in
      cartilaginous fishes.

PMID- 22986828
TI  - Contributions of developmental studies in the dogfish Scyliorhinus canicula to
      the brain anatomy of elasmobranchs: insights on the basal ganglia.
AB  - The basic anatomy of the elasmobranch brain has been previously established after
      studying the organization of the different subdivisions in the adult brain.
      However, despite the relatively abundant immunohistochemical and hodologic
      studies performed in different species of sharks and skates, the organization of
      some brain subdivisions remains unclear. The present study focuses on some brain
      regions in which subdivisions established on the basis of anatomical data in
      adults remain controversial, such as the subpallium, mainly the striatal
      subdivision. Taking advantage of the great potential of the lesser spotted
      dogfish, Scyliorhinus canicula, as a model for developmental studies, we have
      characterized the subpallium throughout development and postembryonic stages by
      analyzing the distribution of immunomarkers for GABA, catecholamines, and
      neuropeptides, such as substance P. Moreover, we have analyzed the expression
      pattern of regulatory genes involved in the regionalization of the telencephalon,
      such as Dlx2, Nkx2.1, and Shh, and followed their derivatives throughout
      development in relation to the distribution of such neurochemical markers. For
      further characterization, we have also analyzed the patterns of innervation of
      the subpallium after applying tract-tracing techniques. Our observations may shed
      light on postulate equivalences of regions and nuclei among elasmobranchs and
      support homologies with other vertebrates.

PMID- 22986829
TI  - Forebrain organization in elasmobranchs.
AB  - It has long been known that many elasmobranch fishes have relatively large
      brains. The telencephalon, in particular, has increased in size in several
      groups, and as a percent of total brain weight, it is as large as in some
      mammals. Little is known, however, about the organization, connections, and
      functions of the telencephalon in elasmobranchs. Early experimental studies
      indicated that olfaction does not dominate the telencephalon and that other
      sensory modalities are represented, particularly in the pallium. We have
      investigated the intrinsic and extrinsic connections of the telencephalon in two
      elasmobranch species: the thornback guitarfish, Platyrhinoidis triseriata, and
      the spiny dogfish, Squalus acanthias. Tracers were injected into various parts of
      the forebrain and olfactory pathways were found to be extensive and were seen to
      involve the pallium. Injections into various parts of the pallium revealed a
      major input from the area basalis, which receives secondary and tertiary
      olfactory fibers. Nonolfactory input from the diencephalon appeared relatively
      minor and seemed to converge with olfactory information in the dorsal pallium and
      area superficialis basalis. Major descending projections were seen to originate
      in the dorsal pallium and terminate in the hypothalamus and - in the case of
      Platyrhinoidis - massively in the lateral mesencephalic nucleus. Descending
      pathways appeared mainly crossed in Platyrhinoidis, but not in Squalus. Our data
      indicate that the concept of the dorsal pallium as a nonolfactory area in
      elasmobranchs must be reconsidered, and we suggest that many telencephalic
      centers, including the dorsal pallium, are involved in olfactory orientation.

PMID- 22986830
TI  - The cerebellum and cerebellum-like structures of cartilaginous fishes.
AB  - The cerebellum is well developed in cartilaginous fishes, with the same cell
      types (barring basket cells) and organizational features found in other
      vertebrate groups, including mammals. In particular, the lattice-like
      organization of cerebellar cortex (with a molecular layer of parallel fibers,
      interneurons, spiny Purkinje cell dendrites, and climbing fibers) is a defining
      characteristic. In addition to the cerebellum, cartilaginous fishes have
      cerebellum-like structures in the dorsolateral wall of the hindbrain. These
      structures are adjacent to and, in part, contiguous with the cerebellum. They are
      cerebellum-like in that they have a molecular layer of parallel fibers and
      inhibitory interneurons that has striking organizational similarities to the
      molecular layer of the cerebellar cortex. However, these structures also have
      characteristics that differ from the cerebellum. For example, cerebellum-like
      structures do not have climbing fibers and are clearly sensory. They receive
      direct afferent input from peripheral sensory receptors and relay their outputs
      to midbrain sensory areas. As a consequence of this close sensory association and
      the ability of researchers to characterize signal processing in these structures
      in a behaviorally relevant context, good progress has been made in determining
      the fundamental processing algorithm of the cerebellum-like structures. This
      algorithm enables the molecular layer to act as an adaptive filter that cancels
      self-generated noise in electrosensory and lateral line systems. Given the
      fundamental similarities of the molecular layer across these structures and the
      phylogeny of these structures across basal vertebrates, it is clear that these
      structures share a common genetic-developmental program. Syngeny is a term that
      has been used to describe similarity of structure due to a shared genetic
      developmental program, whether the structures are phylogenetically homologous or
      not. Given that the cerebellum and cerebellum-like structures are physically
      adjacent, we propose that cerebellum-like structures were the evolutionary
      antecedent of the cerebellum and that the cerebellum arose through a change in
      the genetic-developmental program, amounting to a duplication of existing
      structure. Such duplication to form adjacent structures can be considered a
      special case of syngeny. On this view, the cerebellum is an evolutionary
      innovation in gnathostomes that is literally superimposed on pre-existing
      underlying brain structures and pathways. From this perspective, the cerebellum
      can be considered an example of 'subsumption architecture', a term that describes
      the addition of modules that add computational power while maintaining existing
      fundamental functionality. This addition is reflected in the finding that in
      elasmobranchs with relatively large brains, the size of the telencephalon and
      cerebellum enlarge disproportionately, while those parts of the brain that
      contain more direct sensory and motor connections do not. Added 'computational'
      power in the chondrichthyan brain and the comparative function and evolution of
      the cerebellum and cerebellum-like structures across the cartilaginous fishes
      supports the idea of the cerebellum as an example of subsumption architecture.

PMID- 22986831
TI  - Synthesis and antiproliferative activity of novel alpha-aminophosphonates.
AB  - A novel series of carbazole-based alpha-aminophosphonates were synthesized by
      three component coupling of 6-bromo-9-ethyl-9H-carbazole-3-carbaldehyde, amine
      and diethyl phosphite using polyethylene glycol (PEG-400) as a green reaction
      media. The antiproliferative activity of these molecules was evaluated against
      three cancer cell lines. Of these, compounds 4c, 4e and 4m were found to exhibit
      good antiproliferative activity against three cancer cells, A549, MCF-7, and NCI
      N87.

PMID- 22986832
TI  - Prediction of esophageal variceal bleeding in B-viral liver cirrhosis using the
      P2/MS noninvasive index based on complete blood counts.
AB  - BACKGROUND/AIM: Periodic endoscopy for esophageal varices (EVs) and prophylactic
      treatment of high-risk EVs, i.e., medium/large EVs, small EVs with the red-color
      sign or decompensation, are recommended in cirrhotic patients. We assessed the
      cumulative risks for future EV bleeding using the following simple P2/MS index:
      (platelet count)2/[monocyte fraction (%) * segmented neutrophil fraction (%)].
      METHODS: We enrolled 475 consecutive B-viral cirrhosis patients for 4 years, none
      of whom experienced EV bleeding. All underwent laboratory work-ups, endoscopy and
      ultrasonography. Those with EV bleeding took a nonselective beta-blocker as
      prophylaxis. The major endpoint was the first occurrence of EV bleeding, analyzed
      using the Kaplan-Meier and Cox regression methods. RESULTS: Among patients with
      EV bleeding (n = 131), 25 experienced their first EV bleeding during follow-up.
      To differentiate the risk for EV bleeding, we divided them into two subgroups
      according to their P2/MS value (subgroup 1: P2/MS >=9 and subgroup 2: P2/MS <9).
      The risk was significantly higher in subgroup 2 (p = 0.029). From multivariate
      analysis, a lower P2/MS (p = 0.040) remained a significant predictor for EV
      bleeding along with large varix size (p = 0.015), red-color sign (p = 0.041) and
      Child-Pugh classification B/C (p = 0.001). In subgroup 1, the risk for EV
      bleeding was similar to that of patients with low-risk EVs (p = 0.164).
      CONCLUSIONS: The P2/MS is a reliable predictor for the risk of EV bleeding among
      patients with EV bleeding. According to risk stratification, different
      prophylactic treatments should be considered for the subgroup with a P2/MS <9.

PMID- 22986833
TI  - Detection of Merkel cell polyomavirus in the human tissues from 41 Japanese
      autopsy cases using polymerase chain reaction.
AB  - It has recently been shown that approximately 80% of Merkel cell carcinomas
      harbor a novel polyomavirus named Merkel cell polyomavirus (MCPyV). MCPyV has
      been detected in human tissue samples. However, detailed distribution of MCPyV in
      non-neoplastic Japanese human tissues remains unclear. To address this, we used
      single or real-time quantitative polymerase chain reaction (PCR) for 41 autopsy
      cases. PCR revealed MCPyV-DNA in non-neoplastic samples: total, 29/41 (71%);
      adult, 29/39 (74%); fetus or infant, 0/2; men, 24/28 (86%); women, 5/13 (38%);
      total human tissues, 66/572 (12%); skin, 8/15 (53%); adrenal gland, 9/33 (27%),
      and other 16 organs (4-25%). This study first reported the presence of MCPyV-DNA
      in non-neoplastic tissues of thyroid gland, adrenal gland, spleen, bone marrow,
      stomach, gallbladder, pancreas, heart, and aorta. PCR revealed that viral load
      ranged from 0.00026 to 0.22 in all MCPyV-positive tissues compared with Merkel
      cell carcinoma samples. These detailed PCR data showed higher prevalence of MCPyV
      infection in Japanese men than women (p = 0.004) and broad distribution of MCPyV
      with low viral load in more non-neoplastic human tissues than in the previous
      reports. These data provide valuable insights for further studies of MCPyV
      infection and MCPyV-related diseases.

PMID- 22986834
TI  - Incidence, mode, and location of acute proximal junctional failures after
      surgical treatment of adult spinal deformity.
AB  - STUDY DESIGN: Multicenter, retrospective series. OBJECTIVE: To analyze the
      incidence, mode, and location of acute proximal junctional failures (APJFs) after
      surgical treatment of adult spinal deformity. SUMMARY OF BACKGROUND DATA: Early
      proximal junctional failures above adult deformity constructs are a serious
      clinical problem; however, the incidence and nature of early APJFs remain
      unclear. METHODS: A total of 1218 consecutive adult spinal deformity surgeries
      across 10 deformity centers were retrospectively reviewed to evaluate the
      incidence and nature of APJF, defined as any of the following within 28 weeks of
      index procedure: minimum 15 degrees  post-operative increase in proximal
      junctional kyphosis, vertebral fracture of upper instrumented vertebrae (UIV) or
      UIV + 1, failure of UIV fixation, or need for proximal extension of fusion within
      6 months of surgery. RESULTS: Sixty-eight APJF cases were identified out of 1218
      consecutive surgeries (5.6%). Patients had a mean age of 63 years (range, 26-82
      yr), mean fusion levels of 9.8 (range, 4-18), and mean time to APJF of 11.4 weeks
      (range, 1.5-28 wk). Fracture was the most common failure mode (47%), followed by
      soft-tissue failure (44%). Failures most often occurred in the thoracolumbar
      region (TL-APJF) compared with the upper thoracic region (UT-APJF), with 66% of
      patients experiencing TL-APJF compared with 34% experiencing UT-APJF. Fracture
      was significantly more common for TL-APJF relative to UT-APJF (P = 0.00), whereas
      soft-tissue failure was more common for UT-APJF (P < 0.02). Patients experiencing
      TL-APJF were also older (P = 0.00), had fewer fusion levels (P = 0.00), and had
      worse postoperative sagittal vertical axis (P < 0.01). CONCLUSION: APJFs were
      identified in 5.6% of patients undergoing surgical treatment of adult spinal
      deformity, with failures occurring primarily in the TL region of the spine. There
      is evidence that the mode of failure differs depending on the location of UIV,
      with TL failures more likely due to fracture and UT failures more likely due to
      soft-tissue failures.

PMID- 22986835
TI  - Preoperative vitamin D status of adults undergoing surgical spinal fusion.
AB  - STUDY DESIGN: Retrospective investigation of cross-sectional data. OBJECTIVE: To
      define the prevalence and determinants of preoperative vitamin D deficiency among
      adults undergoing spinal fusion. SUMMARY OF BACKGROUND DATA: Vitamin D plays a
      critical role in establishing optimal bone health, which, in turn, is vital to
      the success of spinal arthrodesis. Recently, hypovitaminosis D was documented in
      43% of adults undergoing any orthopedic surgery. METHODS: Serum 25-hydroxyvitamin
      D levels were routinely measured in adults undergoing spinal fusion at a single
      institution. Between January 2010 and March 2011, 313 patients were
      retrospectively identified for inclusion. Risk factors for vitamin D deficiency
      (<20 ng/mL) were analyzed using univariate analysis and multivariate logistic
      regression. RESULTS: The rates of inadequacy (<30 ng/mL) and deficiency were 57%
      and 27%, respectively. Although 260 patients were diagnosed with degenerative
      disease (spondylosis), 99 had deformity, and there were 73 revision cases. There
      was a higher rate of smoking (P = 0.03) and lower age (P < 0.01) in the vitamin D
      deficient subset. There was no sex difference. Increasing body mass index (P <
      0.01), increasing Neck and Oswestry Disability Index scores (P = 0.03), and lack
      of vitamin D and/or multivitamin supplementation (P < 0.01) remained predictors
      of deficiency after multivariate analysis. Those with previous supplementation
      were older (P < 0.01) and more likely to be at least 50 years old than those
      without repletion (P < 0.01). CONCLUSION: Our investigation revealed a
      substantially high prevalence of vitamin D abnormality in the analyzed
      population. Although advanced age is a well-established risk factor for
      hypovitaminosis, young adults undergoing fusion should not be overlooked with
      regard to vitamin D screening; this age bracket is less likely to have been
      previously supplemented. In the absence of better-recognized determinants, spinal
      disability indices may also be useful in identifying those with deficiency.

PMID- 22986836
TI  - Redefining global spinal balance: normative values of cranial center of mass from
      a prospective cohort of asymptomatic individuals.
AB  - STUDY DESIGN: Prospective radiographical analysis of cranial center of mass
      (CCOM), C2, and C7 plumb lines in young and elderly asymptomatic individuals.
      OBJECTIVE: To establish a normal range for craniosagittal balance for both young
      and elderly asymptomatic individuals. SUMMARY OF BACKGROUND DATA: Global sagittal
      balance must account for the position of the head in relation to the spine and
      pelvis. The C7 plumb line defines thoracolumbar sagittal balance and has been
      shown to have significant impact on patient outcomes. However, the C7 plumb line
      fails to take into consideration the position of the head in relation to the
      pelvis. METHODS: A total of 100 asymptomatic 20- to 40-year-old patients and 100
      asymptomatic 60- to 80-year-old patients were enrolled. Standing plain
      radiographs of 14 * 36 in were obtained. CCOM, C2, and C7 plumb lines were drawn
      and measured from the superoposterior endplate of S1. RESULTS: A total of 78
      asymptomatic 20- to 40-year-old patients and 62 asymptomatic 60- to 80-year-old
      patients had adequate radiographs. The mean plumb line values in the 20- to 40
      year-old patients and 60- to 80-year-old patients, respectively, were as follows;
      CCOM 9.0 mm (SD, 31.5 mm) and 41.2 mm (SD, 35.7 mm); C2 -2.7 mm (SD, 32.7 mm) and
      32.1 mm (SD, 33.6 mm); and C7 -16.4 mm (SD, 31.5 mm) and 10.6 mm (SD, 27.8 mm).
      One-way analysis of variance and Student t tests confirmed that these mean plumb
      line values were significantly different between young and elderly patients (P <
      0.001). The change at each level over time was highly correlated with the other
      levels (r > 0.97; P < 0.001) as did the degree of change between groups (r >
      0.90, P < 0.001). CONCLUSION: Spinopelvic alignment in conjunction with CCOM has
      increased our understanding of spinal balance by including the head and may
      better represent true global spinal balance. CCOM is an easily measured parameter
      by using the nasion-inion technique.

PMID- 22986837
TI  - Prevalence of adjacent segment degeneration after spine surgery: a systematic
      review and meta-analysis.
AB  - STUDY DESIGN: Systematic review of published prevalence of adjacent segment
      degeneration (ASD) after spine surgery. OBJECTIVE: To evaluate the prevalence of
      ASD in patients after cervical and lumbar spine surgery. SUMMARY OF BACKGROUND
      DATA: ASD is a common complication after spine surgery in long-term follow-up. A
      large body of literature has been reported on the topic, but no meta-analysis of
      the epidemiological data on ASD has been published METHODS: We searched the
      MEDLINE until March 2012 published in English language that reported the
      prevalence of ASD after spine surgery. We determined the ASD rates by calculating
      proportions and 95% confidence interval (CI) for each study and then pooled the
      data to derive a pooled proportion and 95% CI. RESULTS: A total of 94 studies
      with 34,716 patients from 19 countries were included. The occurrence of
      radiograph ASD ranged from 4.8% to 92.2%, and the pooled prevalence was 29.3%
      (95% CI, 22.7%-35.8%) by the random-effects model. The occurrence of symptoms ASD
      ranged from 0.0% to 30.3%, and the pooled prevalence was 7.4% (95% CI, 6.4%
      8.5%). In cervical position, the occurrence of radiograph ASD and symptoms ASD
      was 32.8% (95% CI, 17.8%-47.9%) and 6.3% (95% CI, 4.8%-7.8%); in lumbar position,
      the occurrence of radiograph ASD and symptoms ASD was 26.6% (95% CI, 21.3%-31.9%)
      and 8.5% (95% CI, 6.4%-10.7%). In the 0.5- to 2- or less, more than 2- to 5- or
      less, and more than 5- to 20- or less year diagnosis time, the radiograph ASD
      prevalence was 21.8% (16.0%-27.6%), 33.6% (21.8%-45.4%), and 37.4% (10.7%-64.1%),
      respectively; and the symptoms ASD prevalence was 6.5% (4.8%-8.1%), 12.1% (8.2%
      16.0%), and 3.2% (2.5%-4.0%), respectively. CONCLUSION: Spine surgery is
      associated with significant risk of ASD. These figures may be useful in the
      estimation of the burden of the ASD after spine surgery.

PMID- 22986839
TI  - Unknown case: part 2.

PMID- 22986838
TI  - Modified K-line in magnetic resonance imaging predicts insufficient decompression
      of cervical laminoplasty.
AB  - STUDY DESIGN: A retrospective single-center study. OBJECTIVE: To clarify
      preoperative factors predicting unsatisfactory indirect decompression after
      laminoplasty in patients with cervical spondylotic myelopathy. SUMMARY OF
      BACKGROUND DATA: Many authors have shown that inadequate indirect decompression
      after laminoplasty can inhibit neural recovery and should be considered a
      complication. We previously demonstrated that residual anterior compression of
      the spinal cord (ACS) impaired recovery of upper extremity motor function.
      Although the K-line has been established as a predictive index indicating that
      laminoplasty is required in patients with ossification of the posterior
      longitudinal ligament, it remains unclear what preoperative factors can predict
      insufficient posterior cord decompression in patients with cervical spondylotic
      myelopathy. METHODS: Forty-six consecutive patients who underwent laminoplasty
      for the treatment of cervical spondylotic myelopathy at our hospital were
      reviewed. A modified K-line was defined as the line connecting the midpoints of
      the spinal cord at C2 and C7 on a T1-weighted sagittal magnetic resonance image.
      We also determined the minimum interval between the tip of local kyphosis and a
      line connecting the midpoint of the cord at the level of the inferior endplates
      of C2 and C7 (INTmin) on the midsagittal image. Data analysis involved logistic
      regression and receiver operating characteristic curve analysis to select the
      most valuable index for predicting postoperative ACS. RESULTS: Ten patients had
      ACS immediately after laminoplasty. Logistic regression analysis showed that
      INTmin was a significant predictive factor for the occurrence of postoperative
      ACS (odds ratio = 0.485; 95% confidence interval = 0.29-0.81; P = 0.02). Receiver
      operating characteristic curve analysis showed an area under the curve of 0.871.
      A cutoff of 4.0 mm had a sensitivity of 80% and a specificity of 80.6% for
      prediction of postoperative ACS. CONCLUSION: The parameter INTmin correlated with
      the occurrence of postoperative ACS. A cutoff point of 4.0 mm is most appropriate
      for alerting spine surgeons to a high likelihood of postoperative ACS.

PMID- 22986840
TI  - Validation of a patient self-reported screening questionnaire for axial
      spondyloarthropathy in a UK Population.
AB  - STUDY DESIGN: Cross-sectional cohort study. OBJECTIVE: The aim of this study was
      to develop and validate a patient-completed screening questionnaire for axial
      spondyloarthropathy for use in the United Kingdom. SUMMARY OF BACKGROUND DATA:
      Axial spondyloarthropathy (axial SpA) can be difficult to diagnose in the early
      stages of disease, leading to diagnostic delay and morbidity. Existing population
      screening tools lack sensitivity or have not been validated in the UK population.
      METHODS: Questionnaires were sent to 295 patients with definite ankylosing
      spondylitis (meeting modified New York criteria), nonradiographical axial SpA
      (sacroiliitis on magnetic resonance imaging), or mechanical back pain. Responses
      from 190 patients were analyzed. Binary logistic regression was used to develop a
      model differentiating inflammatory from mechanical pain. RESULTS: The final model
      (male sex, onset of symptoms by age 33 years, no radiation of pain, pain gets
      better as day goes on, pain increases with rest, and personal history of iritis)
      correctly classified 86% of cases with Nagelkerke R = 0.486. A numerical score
      (with 1 point assigned for each feature present) was calculated and receiver
      operating characteristic curve was constructed, with area under the curve of
      0.911 (95% confidence interval: 0.87-0.96). A score of >=3/6 had sensitivity of
      75.6% and specificity of 87.9% for inflammation. CONCLUSION: We have developed a
      model that differentiates patients with ankylosing spondylitis/axial SpA from
      those with mechanical spinal disease and can be used as a self-completed
      screening tool.

PMID- 22986841
TI  - Perioperative characteristics, complications, and outcomes of single-level versus
      multilevel thoracic corpectomies via modified costotransversectomy approach.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To compare perioperative end
      points and outcomes of single-level versus multilevel corpectomy performed using
      a modified costotransversectomy approach. SUMMARY OF BACKGROUND DATA: Single
      level corpectomy via posterolateral approach has been shown to be an effective
      alternative to the traditional anterior thoracotomy approach. However, there is a
      paucity of studies that have examined multilevel thoracic corpectomy via
      posterolateral approach. METHODS: Using electronic medical records, we identified
      a consecutive population of adult patients who underwent modified
      costotransversectomy corpectomy in the thoracic region between 2006 and 2009.
      Patients were stratified by number of corpectomies performed into either a single
      level or multilevel group. With the use of baseline descriptive statistics and
      multivariate analysis, perioperative parameters and follow-up outcomes were
      assessed between the 2 groups. RESULTS: A total of 40 patients were included in
      the final analysis, with 25 patients in the single-level group and 15 patients in
      the multilevel group. Mean follow-up was 16.1 months. Overall complication rate
      was 37.5%. Between the 2 groups, there were no significant differences in
      operative time, blood loss, transfusion rate, quantity of blood transfused,
      length of hospital stay, or complication rates. Also, there were no significant
      differences in repeat surgery rate, Medical Research Council strength, Nurick
      score, or pain at most recent follow-up, and all groups gained a comparable
      magnitude of benefit from surgery. CONCLUSION: Multilevel corpectomy via modified
      costotransversectomy approach in the thoracic region is a feasible and effective
      option that does not seem to be associated with significantly increased
      morbidity. The degree of clinical improvement also seems comparable with single
      level corpectomy.

PMID- 22986842
TI  - Cost-effectiveness of single-level anterior cervical discectomy and fusion five
      years after surgery.
AB  - STUDY DESIGN: Longitudinal cohort. OBJECTIVE.: The purpose of this study is to
      determine the cost per quality-adjusted life year (cost/QALY) gained for single
      level instrumented anterior cervical discectomy and fusion (ACDF) over 5 years.
      SUMMARY OF BACKGROUND DATA: Economic value is an increasingly important component
      of health care policy decision making. METHODS: Control patients who had
      undergone ACDF with complete 5-year follow-up data who were part of the
      Investigational Device Exemption trials for cervical disc arthroplasty were
      identified. Direct costs for each intervention reported as part of the trial were
      determined using the 2012 Medicare Fee schedule. Health utility was determined
      using the Short Form-6D, calculated by transformation from the Short Form-36.
      RESULTS: There were 352 patients (182 women, 170 men), mean age was 44.6 years
      (22-73 yr). Cost per patient for the index ACDF was $15,714. Over 5 years, 41
      repeat ACDFs, 15 posterior fusions, 6 foraminotomies, 2 implant removals, 2
      hematoma evacuations, and 1 esophageal fistula repair were performed. Mean QALY
      gained in each year of follow-up was 0.16, 0.18, 0.17, 0.18, and 0.18 for a
      cumulative 0.88 QALY gain over 5 years. The resultant cost/QALY gain at 1 year
      was $104,831; $53,074 at year 2; $37,717 at year 3; $28,383 at year 4; and
      $23,460 at year 5. In this cohort, 11 nerve releases and 26 rotator cuff repairs
      were done within 5 years after the index ACDF. Subanalysis to include upper
      extremity procedures was performed. The cost/QALY gained at 1 year including
      upper extremity procedures was $106,256; $54,622 at year 2; $38,836 at year 3;
      $29,454 at year 4; and $24,479 at year 5. CONCLUSION: Increasing health care
      costs call for demonstration of cost-effectiveness in order to justify payment
      for interventions, including ACDFs. This study indicates that at 5-year follow
      up, single-level instrumented ACDF is both effective and durable resulting in a
      favorable cost/QALY gained as compared to other widely accepted health care
      interventions.

PMID- 22986843
TI  - Intraoperative pelvic brachytherapy for treatment of locally advanced or
      recurrent colorectal cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and morbidity of
      intraoperative radiation therapy (IORT) for advanced colorectal cancer. METHODS:
      All patients undergoing IORT for locally advanced rectal cancer from 2001-2009
      were reviewed for cancer recurrence, survival, and procedure-related morbidity.
      Cumulative event rates were estimated using the method of Kaplan and Meier.
      RESULTS: Twenty-nine patients with locally advanced (n = 8) or recurrent (n = 21)
      rectal cancers were treated with IORT and resection. Surgical interventions
      included low anterior resection, abdominoperineal resection, pelvic exenteration,
      and a variety of non-anatomic resections of pelvic recurrences. R(0) resections
      were achieved in 16 patients, while R(1) resections were achieved in 10, and
      margins were grossly positive in 3 patients. IORT was delivered to all patients
      over a median area of 48 (42-72) cm(2) at a median dose of 12 (12-15) Gy. Local
      and overall recurrence rates were 24 % (locally advanced group) and 45 %
      (recurrent group). Median disease-free and overall survival were 25 and 40 months
      respectively at a median follow-up of 26 (18-42) months. The short-term (<=30
      days) complication rate was 45 %. Eight patients developed local wound
      complications, 5 of which required operative intervention. Four patients
      developed intra-abdominal abscesses requiring drainage. Long-term (>30 days)
      complications were identified in 11 patients (38 %) and included long-term wound
      complications (n = 3), ureteral obstruction requiring stenting (n = 1),
      neurogenic bladder (n = 3), enteric fistulae (n = 2), small bowel obstruction (n
      = 1), and neuropathic pain (n = 1). CONCLUSIONS: Intraoperative brachytherapy is
      a viable IORT option during pelvic surgery for locally advanced or recurrent
      colorectal cancer but is associated with high postoperative morbidity. Whether
      intraoperative brachytherapy can improve local recurrence rates for locally
      advanced or recurrent colorectal cancer will require further prospective
      investigation.

PMID- 22986844
TI  - Combined screening for preeclampsia and small for gestational age at 11-13 weeks.
AB  - OBJECTIVE: To combine a specific algorithm for small for gestational age (SGA)
      without preeclampsia (PE) and another algorithm for PE in the prediction of SGA
      and PE. METHODS: This was a screening study of singleton pregnancies at 11-13
      weeks including 1,426 (2.3%) that subsequently developed PE, 3,168 (5.1%) that
      delivered SGA neonates and 57,458 that were unaffected by PE and SGA. We
      developed a prediction algorithm for SGA requiring delivery before 37 weeks'
      gestation (preterm-SGA) from maternal characteristics, uterine artery pulsatility
      index, mean arterial pressure, serum pregnancy-associated plasma protein-A and
      placental growth factor multiple of the median values. We then examined the
      performance of this algorithm individually and in combination with a previously
      reported algorithm for early-PE in the prediction of SGA and PE. RESULTS: When
      screen positivity was defined by risk cutoff of 1:200 using the algorithm for
      early-PE and the risk cutoff of 1:150 using the algorithm for preterm-SGA, the
      false positive rate was 10.9% and the detection rates of early-PE, late-PE,
      preterm-SGA and term-SGA were 95.3, 45.6, 55.5 and 44.3%, respectively.
      CONCLUSIONS: Effective first-trimester screening for early-PE and preterm-SGA can
      be provided by the combined use of the specific algorithms.

PMID- 22986848
TI  - Treatment of recalcitrant eosinophilic cellulitis with adalimumab.

PMID- 22986850
TI  - Effect of dermoscopy education on the ability of medical students to detect skin
      cancer.
AB  - OBJECTIVES: To determine students' ability to discriminate benign vs malignant
      lesions and to assess attitudes regarding skin cancer examination (SCE). DESIGN:
      Second-year medical students at 1 institution participated in an SCE intervention
      for 2 consecutive years. INTERVENTION: Cohort 1 received intervention A,
      consisting of SCE teaching without a dermoscopy tutorial. Cohort 2 received
      intervention B, consisting of SCE teaching with a dermoscopy tutorial, access to
      online dermoscopy resources, and a dermoscope. MAIN OUTCOME MEASURE: Surveys
      before and after the lecture included an image-based test of 10 lesions to assess
      ability to differentiate benign from malignant lesions. RESULTS: There were 130
      participants from cohort 1 and 131 participants from cohort 2 at the
      postintervention survey. At baseline, students in both groups reported similar
      attitudes regarding the value of SCE (P = .05) and intention to perform SCE on
      patients (P = .55). Overall, cohort 2 exhibited improvement (P < .001) from
      preintervention (52.0% correct) to postintervention assessments (63.0% correct),
      whereas cohort 1 did not (47.0% and 46.0% correct, respectively; P = .50).
      Although both groups improved (P < .001) in the diagnosis of the superficial
      spreading melanoma, cohort 2 improved in the diagnosis of the basal cell
      carcinoma (P < .001) and cohort 1 displayed deterioration in identifying the
      malignant nature of this lesion (P < .001). For the nodular melanoma, correct
      diagnosis decreased significantly in cohort 1 (P < .001) and negligibly in cohort
      2 (P = .90). CONCLUSIONS: Students receiving the dermoscopy tutorial improve in
      diagnosis of cutaneous lesions compared with those not receiving the dermoscopy
      intervention. Teaching SCE with inclusion of dermoscopy may be an effective means
      of enhancing skin cancer knowledge.

PMID- 22986852
TI  - Effect of teledermatology on the prognosis of patients with cutaneous melanoma.
AB  - OBJECTIVE: To evaluate differences in the initial prognosis of patients with
      cutaneous melanoma managed by teledermatology (TD) vs other non-TD referral
      systems. DESIGN: Descriptive and longitudinal study of a store-and-forward TD
      system aimed at the triage of patients with suspicious pigmented lesions.
      SETTING: In 2003, a store-and-forward TD triage system aimed at the selection of
      patients with skin growths suggestive of cancer was implemented at a skin cancer
      clinic. This system has been shown to be accurate and reliable and able to
      significantly shorten waiting periods for consultation with a dermatologist.
      PARTICIPANTS: Patients with primary cutaneous melanoma referred to the Melanoma
      Clinic of the Dermatology Unit, Hospital Universitario Virgen Macarena, Seville,
      Spain, by TD or non-TD tracks were included in the study. MAIN OUTCOME MEASURES:
      Decisions on the referral of patients with suspicious skin lesions by store-and
      forward TD vs by a conventional referral system. Breslow thickness and tumor
      stage were recorded in each study group (TD and non-TD) and were compared.
      RESULTS: Two hundred one patients with primary cutaneous melanoma were enrolled
      in the study. In total, 33.3% were managed at their primary care center by
      teleconsultation, whereas 66.7% were managed by a conventional referral system.
      The mean Breslow thickness was significantly lower among patients in the TD group
      than among patients in the non-TD group (1.06 vs 1.64 mm, P = .03). The frequency
      of melanoma with a favorable initial prognosis (tumor stages Tis and T1a) was
      significantly higher in the TD group (70.1% vs 56.9%, P = .03). The odds ratio of
      having a cutaneous melanoma with a favorable initial prognosis in the TD group
      was 1.96 (95% CI, 1.14-3.50; P = .04). CONCLUSION: Teledermatology as a screening
      system for cutaneous melanoma has a favorable effect on the initial prognosis of
      patients with melanoma.

PMID- 22986853
TI  - Top-accessed article: dressings for acute and chronic wounds.

PMID- 22986855
TI  - Transverse nasal crease and transverse nasal milia: clinical variants of the same
      entity.
AB  - BACKGROUND: Transverse nasal crease is an uncommonly reported entity. It likely
      represents an embryologic fault line. Transverse nasal milia have also been
      reported in the same location, both as an isolated finding and in a transverse
      nasal crease. This observation suggests they are variants of the same entity.
      OBSERVATIONS: Two cases, one of transverse nasal crease with milia and one of
      transverse nasal milia in the absence of a crease, are reported. A review of the
      literature on these rarely reported conditions was performed. CONCLUSIONS: It is
      important for clinicians to be aware of transverse nasal creases, since they may
      be encountered in a dermatologic practice. Transverse nasal creases, milia in
      transverse nasal creases, transverse nasal milia, and transverse nasal comedones
      in the absence of a transverse nasal crease are likely variants of the same
      entity. They most probably occur because the triangular cartilage and the alar
      cartilage attach in a linear fashion at the junction of the middle and lower
      third of the nose. This produces a potential embryonic fault line in which
      retention cysts presenting as milia and comedones can occur. These clinical
      presentations merit attention because they are likely much more common than
      reported.

PMID- 22986857
TI  - Intertriginous mycosis fungoides: a distinct presentation of cutaneous T-cell
      lymphoma that may be caused by malignant follicular helper T cells.
AB  - BACKGROUND: Follicular helper T cells are a subset of helper T cells that
      facilitate B-cell recruitment and maturation. Rare cases of cutaneous T-cell
      lymphoma manifesting as de novo tumor lesions in intertriginous skin contain an
      infiltrate rich in B cells. These cases may represent malignant counterparts of
      skin-homing follicular helper T cells. OBSERVATIONS: Two men and 1 woman (age
      range, 35-58 years) were seen with predominantly intertriginous tumor-stage
      cutaneous T-cell lymphoma lesions characterized by the absence of epidermotropism
      and the presence of a mixed infiltrate rich in B cells. Two of the patients died
      of the disease less than 3 years from the initial diagnosis. The surviving
      patient has aggressive disease and underwent hematopoietic stem cell
      transplantation. Two of the patients had a prominent CXCL13+, Bcl6/CD3+, and
      programmed death protein 1-positive follicular helper T-cell population.
      CONCLUSIONS: The intertriginous tumor variant of cutaneous T-cell lymphoma is
      heterogeneous but may be associated in some cases with a follicular helper T-cell
      immunophenotype. These patients may follow an aggressive clinical course. Tumor
      progression in sanctuary sites on patients receiving phototherapy may manifest as
      a similar clinical phenotype. Further characterization of the disease process is
      needed to confirm this observation.

PMID- 22986858
TI  - Hair breakage as a presenting sign of early or occult central centrifugal
      cicatricial alopecia: clinicopathologic findings in 9 patients.
AB  - BACKGROUND: Central centrifugal cicatricial alopecia is the most common form of
      cicatricial alopecia in African American women. Treatment options are limited and
      mostly aimed at halting further hair loss but rarely result in hair regrowth.
      Therefore, it is important to recognize early clinical signs, perform a
      confirmatory biopsy, and begin treatment promptly. We have observed that hair
      breakage may be a key sign of early central centrifugal cicatricial alopecia, and
      this association is not clearly described in the literature. OBSERVATIONS: Nine
      patients with hair breakage on the vertex with or without scalp symptoms
      underwent scalp biopsies as part of their evaluation. Of these, 8 had histologic
      samples adequate for complete interpretation: 5 specimens (63%) showed histologic
      changes typical of central centrifugal cicatricial alopecia, with 1 of these
      showing advanced end-stage changes of cicatricial alopecia. Two (25%) revealed
      premature desquamation of the inner root sheath as the sole finding suggestive of
      early central centrifugal cicatricial alopecia and 1 (13%) was normal.
      CONCLUSIONS: Although hair breakage can have multiple causes, early central
      centrifugal cicatricial alopecia must be considered in the differential
      diagnosis, particularly in women of African ancestry. Histologic evaluation may
      reveal early or late findings that can help establish the diagnosis.

PMID- 22986859
TI  - Efficacy of Mohs micrographic surgery for the treatment of dermatofibrosarcoma
      protuberans: systematic review.
AB  - OBJECTIVE To summarize evidence about the recurrence of dermatofibrosarcoma
      protuberans (DFSP) following Mohs micrographic surgery (MMS). DATA SOURCES
      MEDLINE, Cochrane Library, EMBASE, Pascal, Biosis, CisMef, BDSP, Scopus, and Web
      of Knowledge databases were searched for the period January 1, 1995, to August
      31, 2011. Search terms were Mohs micrographic surgery, dermatofibrosarcoma
      protuberans, and their synonyms. No language restriction was used. STUDY
      SELECTION Two of us selected randomized controlled trials or nonrandomized trials
      comparing the recurrence of DFSP among patients undergoing MMS vs wide local
      excision. The search retrieved 384 references, of which 31 were reviewed in
      detail. DATA EXTRACTION Twenty-three nonrandomized trials (4 comparative and 19
      noncomparative) were included, from which data were extracted by 2 of us
      independently. The methodological quality was assessed using the Cochrane
      Handbook for Systematic Reviews of Interventions. DATA SYNTHESIS Moderate-quality
      evidence (level B) was found for recurrence of DFSP after MMS (1.11%; 95% CI,
      0.02%-6.03%) vs after wide local excision (6.32%, 95% CI, 3.19%-11.02%). A mean
      raw recurrence rate of 1.03% (95% CI, 0.37%-2.22%) was found after MMS among 19
      nonrandomized noncomparative trials (low-quality evidence [level C]). The mean
      follow-up periods ranged from 26 to 127 months. The mean time to recurrence was
      68 months. CONCLUSIONS A weak recommendation is given in favor of MMS or similar
      surgical techniques with meticulous histologic evaluation of all margins as the
      first-line therapy for DFSP, particularly in recurrence-prone regions. Attention
      should be given to longer than a 5-year follow-up period. High-quality trials
      with sufficient follow-up periods should be encouraged.

PMID- 22986860
TI  - Practice gaps. Underuse of Mohs micrographic surgery for the treatment of
      dermatofibrosarcoma protuberans: comment on "efficacy of mohs micrographic
      surgery for the treatment of dermatofibrosarcoma protuberans".

PMID- 22986861
TI  - Efficacy and safety of spinosad cream rinse for head lice.

PMID- 22986862
TI  - Efficacy and safety of spinosad cream rinse for head lice-reply.

PMID- 22986863
TI  - Chronic hyperpigmented scaly plaques. Pityriasis rotunda (PR).

PMID- 22986864
TI  - Soft subcutaneous plantar masses. Precalcaneal congenital fibrolipomatous
      hamartoma (PCFH).

PMID- 22986865
TI  - Pruritic scaly plaques in a 75-year-old Hispanic man. Enterobius vermicularis
      (pinworm).

PMID- 22986866
TI  - Fatigue and lower-extremity ecchymosis in a 36-year-old woman. Scurvy.

PMID- 22986871
TI  - Incidence of moderate to severe ichthyosis in the United States.

PMID- 22986872
TI  - A call for consistent reporting of regression in melanoma.

PMID- 22986873
TI  - Comparison of diagnostic and management sensitivity to melanoma between
      dermatologists and MelaFind: a pilot study.

PMID- 22986874
TI  - The safety and efficacy of diphencyprone for the treatment of alopecia areata in
      children.

PMID- 22986875
TI  - Initial presentation of DRESS: often misdiagnosed as infections.

PMID- 22986876
TI  - Enhancing patients' satisfaction and sun-protective behaviors using the ABC
      method of physician-patient communication.

PMID- 22986877
TI  - Effects of anti-tumor necrosis factor therapy on body composition and insulin
      sensitivity in patients with psoriasis.

PMID- 22986878
TI  - Pitfalls of evidence-based medicine revisited.

PMID- 22986879
TI  - On dermatologist density and melanoma mortality.

PMID- 22986881
TI  - Scarring alopecia of the sideburns: a unique presentation of frontal fibrosing
      alopecia in men.

PMID- 22986882
TI  - Lepromatous leprosy in a 26-year-old man with concurrent disseminated
      tuberculosis.

PMID- 22986883
TI  - Case series demonstrating improvement in chronic cutaneous sarcoidosis following
      treatment with TNF inhibitors.

PMID- 22986884
TI  - Antimalarial myopathy in amyopathic dermatomyositis.

PMID- 22986885
TI  - Perniosis induced by a cold-therapy system.

PMID- 22986886
TI  - The "signature" pattern of multiple Basal cell carcinomas.

PMID- 22986887
TI  - Letting children sip: understanding why parents allow alcohol use by elementary
      school-aged children.
AB  - OBJECTIVES: To investigate prosipping beliefs about alcohol among parents and the
      relations among these beliefs, parents' alcohol-specific attitudes and practices,
      and children's reports of initiation of alcohol use. DESIGN: Telephone interview
      study of parent-child dyads. Data for the present study are from the baseline
      interviews of a 4-year intervention trial. SETTING: Southeastern United States.
      PARTICIPANTS: One thousand fifty pairs of mothers or mother surrogates and their
      third-grade children who were recruited for the 4-year intervention trial. MAIN
      OUTCOME MEASURES: Key measures from parents included prosipping beliefs (ie,
      beliefs that sipping alcohol has protective consequences for children), attitudes
      about children's sipping, and parenting practices that affect children's
      opportunity to try alcohol. The key measure from children was experience sipping
      beer, wine, or other types of alcohol. RESULTS: The belief among mothers that
      allowing children to sip alcohol can have protective consequences for children,
      including making children less likely to drink as adolescents and making them
      better at resisting peer influence to drink, ranged from approximately 15% to
      almost 40%. Alcohol use was reported by 32.8% of children. A strong, significant
      association was found between parental prosipping beliefs and children's reported
      alcohol use. CONCLUSIONS: The notion that early exposure to alcohol can be
      beneficial has a strong foothold among some parents of elementary school-aged
      children. More research is needed to understand how parents acquire prosipping
      beliefs and to test messages that effectively modify such beliefs and associated
      prosipping attitudes and practices among parents.

PMID- 22986888
TI  - One dodecahedral bismuth(III) complex derived from 2-acetylpyridine N(4)
      pyridylthiosemicarbazone: synthesis, crystal structure and biological evaluation.
AB  - One dodecahedral bismuth(III) complex [Bi(HL)(NO(3))(3)] (1) (HL = 2
      acetylpyridine N(4)-pyridylthiosemicarbazone) has been synthesized and
      structurally characterized. The analytical data reveals the formation of 1 : 1
      (metal : ligand) stoichiometry. The bismuth(III) ion is nine-coordinated by one
      electron pair (6s(2)) of the bismuth(III) atom, two nitrogen and one sulfur atoms
      from the N(2)S tridentate ligand and five oxygen atoms from three nitrate ions.
      Biological studies, carried out in vitro against eight selected bacteria, and
      four human cancer cells, respectively, have indicated that 1 shows better growth
      inhibiting properties. Upon further investigation, 1 might produce cytotoxicity
      through apoptosis.

PMID- 22986889
TI  - Complementary and alternative medicine in diabetes care.
AB  - Growing numbers of people with diabetes in the U.S. and worldwide use
      complementary and alternative medicine (CAM) while receiving conventional medical
      therapy as a means of managing disease and improving quality of life. Although
      herbal and natural products are the most commonly used forms of CAM, mind-body
      approaches are also gaining popularity and scientific interest. Current findings
      suggest that CAM may help to promote an integrative, participatory model of
      diabetes care that relies upon provider knowledge of evidence-based therapies and
      patient disclosure of CAM use. Emerging evidence of positive findings with some
      natural products and mind-body therapies have been reported in glycemic
      parameters, markers of cardiovascular risk, and quality of life in individuals
      with type 2 diabetes; however, further investigation in well-designed, adequately
      powered studies is needed before use of CAM modalities can be recommended as part
      of clinical care.

PMID- 22986890
TI  - Spatial aspects in the SMAD signaling pathway.
AB  - Among other approaches, differential equations are used for a deterministic
      quantitative description of time-dependent biological processes. For
      intracellular systems, such as signaling pathways, most existing models are based
      on ordinary differential equations. These models describe temporal processes,
      while they neglect spatial aspects. We present a model for the SMAD signaling
      pathway, which gives a temporal and spatial description on the basis of reaction
      diffusion equations to answer the question whether cell geometry plays a role in
      signaling. In this article we simulate the ordinary differential equations as
      well as partial differential equations of parabolic type with suile numerical
      methods, the latter on different cell geometries. In addition to manual
      construction of idealized cells, we also construct meshes from microscopy images
      of real cells. The main focus of the paper is to compare the results of the model
      without and with spatial aspects to answer the addressed question. The results
      show that diffusion in the model can lead to significant intracellular gradients
      of signaling molecules and changes the level of response to the signal transduced
      by the signaling pathway. In particular, the extent of these observations depends
      on the geometry of the cell. 

PMID- 22986891
TI  - Necessary and sufficient conditions for R0 to be a sum of contributions of
      fertility loops.
AB  - Recently, de-Camino-Beck and Lewis (Bull Math Biol 69:1341-1354, 2007) have
      presented a method that under certain restricted conditions allows computing the
      basic reproduction ratio R0 in a simple manner from life cycle graphs, without,
      however, giving an explicit indication of these conditions. In this paper, we
      give various sets of sufficient and generically necessary conditions. To this
      end, we develop a fully algebraic counterpart of their graph-reduction method
      which we actually found more useful in concrete applications. Both methods, if
      they work, give a simple algebraic formula that can be interpreted as the sum of
      contributions of all fertility loops. This formula can be used in e.g. pest
      control and conservation biology, where it can complement sensitivity and
      elasticity analyses. The simplest of the necessary and sufficient conditions is
      that, for irreducible projection matrices, all paths from birth to reproduction
      have to pass through a common state. This state may be visible in the state
      representation for the chosen sampling time, but the passing may also occur in
      between sampling times, like a seed stage in the case of sampling just before
      flowering. Note that there may be more than one birth state, like when plants in
      their first year can already have different sizes at the sampling time. Also the
      common state may occur only later in life. However, in all cases R0 allows a
      simple interpretation as the expected number of new individuals that in the next
      generation enter the common state deriving from a single individual in this
      state. We end with pointing to some alternative algebraically simple quantities
      with properties similar to those of R0 that may sometimes be used to good effect
      in cases where no simple formula for R0 exists.

PMID- 22986892
TI  - The equivalence of two phylogenetic biodiversity measures: the Shapley value and
      Fair Proportion index.
AB  - Most biodiversity conservation programs are forced to prioritise species in order
      to allocate their funding. This paper contains a mathematical proof that provides
      biological support for one common approach based on phylogenetic indices.
      Phylogenetic trees describe the evolutionary relationships between a group of
      taxa. Two indices for computing the distinctiveness of each taxon in a
      phylogenetic tree are considered here-the Shapley value and the Fair Proportion
      index. These indices provide a measure of the importance of each taxon for
      overall biodiversity and have been used to prioritise taxa for conservation. The
      Shapley value is the biodiversity contribution a taxon is expected to make if all
      taxa are equally likely to become extinct. This interpretation makes it appealing
      to use the Shapley value in biodiversity conservation applications. The Fair
      Proportion index lacks a convenient interpretation, however it is significantly
      easier to calculate and understand. It has been empirically observed that there
      is a high correlation between the two indices. This paper shows the mathematical
      basis for this correlation and proves that as the number of taxa increases, the
      indices become equivalent. Consequently in biodiversity prioritisation the
      simpler Fair Proportion index can be used whilst retaining the appealing
      interpretation of the Shapley value. 

PMID- 22986893
TI  - The interplay between tissue growth and scaffold degradation in engineered tissue
      constructs.
AB  - In vitro tissue engineering is emerging as a potential tool to meet the high
      demand for replacement tissue, caused by the increased incidence of tissue
      degeneration and damage. A key challenge in this field is ensuring that the
      mechanical properties of the engineered tissue are appropriate for the in vivo
      environment. Achieving this goal will require detailed understanding of the
      interplay between cell proliferation, extracellular matrix (ECM) deposition and
      scaffold degradation. In this paper, we use a mathematical model (based upon a
      multiphase continuum framework) to investigate the interplay between tissue
      growth and scaffold degradation during tissue construct evolution in vitro. Our
      model accommodates a cell population and culture medium, modelled as viscous
      fluids, together with a porous scaffold and ECM deposited by the cells,
      represented as rigid porous materials. We focus on tissue growth within a
      perfusion bioreactor system, and investigate how the predicted tissue composition
      is altered under the influence of (1) differential interactions between cells and
      the supporting scaffold and their associated ECM, (2) scaffold degradation, and
      (3) mechanotransduction-regulated cell proliferation and ECM deposition.
      Numerical simulation of the model equations reveals that scaffold heterogeneity
      typical of that obtained from [Formula: see text]CT scans of tissue engineering
      scaffolds can lead to significant variation in the flow-induced mechanical
      stimuli experienced by cells seeded in the scaffold. This leads to strong
      heterogeneity in the deposition of ECM. Furthermore, preferential adherence of
      cells to the ECM in favour of the artificial scaffold appears to have no
      significant influence on the eventual construct composition; adherence of cells
      to these supporting structures does, however, lead to cell and ECM distributions
      which mimic and exaggerate the heterogeneity of the underlying scaffold. Such
      phenomena have important ramifications for the mechanical integrity of engineered
      tissue constructs and their suitability for implantation in vivo. 

PMID- 22986894
TI  - A comprehensive review of everolimus clinical reports: a new mammalian target of
      rapamycin inhibitor.
AB  - As new immunosuppressive agents are introduced to the market, clinicians are
      faced with the daunting task of sifting through the published literature to
      decide the value that the agent will add to their own practice. We often must
      extrapolate information provided through study in other solid-organ
      transplantation populations than our specific area of interest as we interpret
      the results and outcomes. With these challenges in mind, this compilation of
      published work for the newest mammalian target of rapamycin inhibitor everolimus
      (Certican; Novartis Pharmaceuticals, Hanover, NJ) (Zortress; Novartis
      Pharmaceuticals, Basel, Switzerland) is intended to provide a concise but
      thorough presentation of available literature so that the reader who may be
      unfamiliar with the agent can make their own judgment. Both Ovid and PubMed
      search engines were queried with a particular focus on high-impact articles noted
      in the Web of Science or Citation Index. Work described solely in abstract or
      case report form was excluded, as well as meta-analyses or those that were
      editorial or commentary in nature. Included were publications presented using the
      English language that described adult human subjects who received a heart, lung,
      kidney, or liver allograft. The goal of this strategy was to allow for the
      inclusion of pertinent literature in an unbiased fashion. Tables are provided
      that outline trial specific information, leaving a discussion of major outcomes
      to the text of the review.

PMID- 22986896
TI  - Inter-individual variance and cardiac cycle dependency of aortic root dimensions
      and shape as assessed by ECG-gated multi-slice computed tomography in patients
      with severe aortic stenosis prior to transcatheter aortic valve implantation: is
      it crucial for correct sizing?
AB  - To evaluate the inter-individual variance and the variability of the aortic root
      dimensions during the cardiac cycle by computed tomography (CT) in patients with
      severe aortic stenosis prior to transcatheter aortic valve implantation (TAVI).
      Fifty-six patients (m/w = 16/40, 81 +/- 6.8 years), scheduled for a transapical
      aortic valve implantation with available preprocedural ECG-gated CT were
      retrospectively included. The evaluation included sizing of the aortic annulus
      and the aortic sinus, measurements of the coronary topography, aortic valve
      planimetry and scoring of calcification. The new defined aortic annulus
      sphericity ratio revealed a mostly elliptical shape with increasing diastolic
      deformation. The calculated effective diameter (ED), determined from the annulus'
      lumen area, turned out to be the parameter least affected from cardiac cycle
      changes while systolic and diastolic annulus dimensions and shape (diameter and
      area) differed significantly (p < 0.001). In about 70 % of the patients with
      relevant paravalvular leaks the finally implanted prosthesis was too small
      according to the CT based calculated ED. The ostial height of the coronaries
      showed a high variability with a critical minimum range <5 mm. The degree of the
      aortic calcification did not have an influence on the aortic annulus deformation
      during the cardiac cycle, but on the occurrence of paravalvular leaks. The aortic
      root anatomy demonstrated a high inter-individual variability and cardiac cycle
      dependency. These results must be strongly considered during the patient
      evaluation prior to TAVI to avoid complications. The systolic effective diameter,
      as measured by ECG-gated CT, represents an appropriate parameter for sizing the
      aortic annulus.

PMID- 22986897
TI  - The expression of metabolism-related proteins in phyllodes tumors.
AB  - The purpose of this study was to investigate the association between the
      expression of hypoxia-inducible factor (HIF)-1alpha, insulin-like growth factor
      (IGF)-1, glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX), and
      monocarboxylate transporter (MCT)4, which are metabolism-related proteins in
      phyllodes tumors (PTs), and clinicopathologic factors and its implication. We
      used tissue microarrays to analyze 207 PTs and performed immunohistochemical
      staining against the glycolysis-related molecules HIF-1alpha, IGF-1, Glut-1,
      CAIX, and MCT4. We then compared the immunohistochemical results and
      clinicopathologic parameters. The expressions of HIF-1alpha, Glut-1, CAIX, and
      MCT4 in the stromal component of PTs increased (P = 0.019, P < 0.001, P = 0.045,
      and P < 0.001, respectively) with increasing tumor grade. According to univariate
      analysis, factors associated with shorter disease-free survival were Glut-1
      expression (P = 0.001) and MCT4 expression (P < 0.001) in the stromal component,
      and the factors associated with shorter overall survival were IGF-1 expression (P
      = 0.012), Glut-1 expression (P < 0.001), CAIX expression (P = 0.039), and MCT4
      expression (P < 0.001) in the stromal component. Our investigation of stromal
      expression of the metabolism-related proteins HIF-1alpha, IGF-1, Glut-1, CAIX,
      and MCT4 revealed that, as the PT grade increased, the stromal expression of HIF
      1alpha, Glut-1, CAIX, and MCT4 significantly increased. This result suggested
      that increasing PT grade is associated with increased glycolysis in the stromal
      component.

PMID- 22986898
TI  - Mature teratoma in association with neural tube defect (occipital encephalocele):
      series of four cases and review of the literature.
AB  - Both occipital encephalocele and teratomas are midline congenital malformations.
      Encephalocele is a form of neural tube defect in which there is a congenital
      defect of the cranium through which occurs a protrusion of brain matter or
      meninges, while teratoma is a tumor derived from all three germ layers. The
      association between occipital encephalocele and teratoma has not been reported to
      date. In the present study, the authors present a series of four such cases.

PMID- 22986899
TI  - Perforation and postoperative bleeding of endoscopic submucosal dissection in
      gastric tumors: analysis of 1190 lesions in low- and high-volume centers in Saga,
      Japan.
AB  - BACKGROUND: This retrospective study aimed to determine risk factors associated
      with serious complications of endoscopic submucosal dissection of gastric tumors
      in multicenters compared between high- and low-volume centers. METHODS: Between
      2001 and 2010, gastric endoscopic submucosal dissection was performed in 1190
      lesions of 1082 patients in five hospitals in Saga, three high-volume and two low
      volume centers. Risk factors for serious complications were evaluated. Patients'
      background characteristics were evaluated, including anticoagulants use and
      underlying diseases. RESULTS: Postoperative bleeding was detected in 75 patients
      (6.9%), and perforation was detected in 40 patients (3.7%). Most postoperative
      bleeding and perforation cases were recovered with endoscopic procedures,
      although one case of each complication was treated by emergency surgery.
      Multivariate analysis indicated that risk factors for perforation were tumor
      location, massive submucusal invasion, endoscopists' experience of 100-149 cases
      and hypertension, and that risk factors for postoperative bleeding were tumor
      location, resected tumor size, and scar lesion. The serious complications were
      not different between high- and low-volume centers. CONCLUSIONS: The present
      study indicated that risk factors for perforation during endoscopic submucosal
      dissection were tumor, endoscopist and patient related, although risk factors for
      postoperative bleeding were tumor related. There was no difference in
      complications between high- and low-volume centers.

PMID- 22986901
TI  - Triterpenoids functionalized at C-2 as diagenetic transformation products of 2,3
      dioxygenated triterpenoids from higher plants in buried wood.
AB  - Several oleanane-related triterpenoids bearing a unique C-2 oxygenated
      functionality have been identified as the predominant triterpenoids from a 4900
      year old oak wood sample buried in a freshwater sediment. They likely represent
      specific molecular tools that can be used as markers to reconstruct past
      vegetation assemblages, or to recognise severely altered oak wood at
      archaeological sites.

PMID- 22986900
TI  - My journey as urogynaecologist.

PMID- 22986902
TI  - Distinct distribution and localization of Rho-kinase in mouse epithelial, muscle
      and neural tissues.
AB  - The small GTP-binding protein Rho plays a crucial role in a wide variety of
      cellular functions through various effector proteins. Rho-kinase is a key
      effector protein of Rho, which is composed of two isoforms, ROCK1 and ROCK2. To
      clarify the site of action of ROCK1 and ROCK2, we performed immunofluorescence
      and immunoelectron microscopic analyses using isoform-specific antibodies in
      mouse tissues. In the large and small intestines, ROCK1 immunoreactivity was
      predominantly identified in epithelial cells, and ROCK2 immunoreactivity was
      negligible. In these epithelial cells, ROCK1 immunoreactivity was distributed on
      plasma membranes, while ROCK1 immunogold signals were localized at cell-cell
      contacts and cell adhesion sites, especially at the adherens junctions at the
      ultrastructural level. In the bladder epithelium, however, ROCK1 and ROCK2
      signals were identified at intermediate filaments, and ROCK2 signals were also
      observed in nuclei. In the three types of muscular cells-smooth, cardiac, and
      skeletal muscle cells-ROCK1 and ROCK2 also showed differential distribution.
      ROCK1 signals were localized at actin filaments, plasma membranes, and vesicles
      near plasma membranes in smooth muscle cells; at the lysosomes in skeletal muscle
      cells; and were undetectable in cardiac muscle cells. ROCK2 signals were
      localized at actin filaments and centrosomes in smooth muscle cells, at
      intercalated discs in cardiac muscle cells, and at Z-discs and sarcoplasmic
      reticulum in skeletal muscle cells. In the brain, ROCK1 immunoreactivity was
      distributed in glia, whereas ROCK2 immunoreactivity was observed in neurons.
      These results indicate that the two isoforms of Rho-kinase distribute
      differentially to accomplish their specific functions.

PMID- 22986904
TI  - Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: The peptidylarginine deiminase 4 (PAD4) gene and PAD4 autoantibodies
      have been associated with rheumatoid arthritis (RA) and its pathogenesis.
      Therefore, methods for accurately determining their levels in the peripheral
      blood of these patients would be a diagnostic asset. The objective of our study
      was to adapt the enzyme-linked immunosorbent assay (ELISA) method for evaluating
      PAD4 levels in human blood. METHODS: We prepared recombinant human (h)PAD1, -2, 
      3, and -4 proteins to develop mouse monoclonal antibodies specific to hPAD4. We
      then generated six monoclonal antibodies against hPAD4 and developed two new
      sandwich ELISA methods for evaluating hPAD4 and PAD4 autoantibodies in the
      peripheral blood from 32 patients with RA, ten patients with osteoarthrosis, and
      20 healthy individuals. RESULTS: The distribution of hPAD4 in the patients'
      plasma was determined. Two populations were identified: one group with high hPAD4
      levels (>0.57 ng/mL) and a second group with near-zero levels (<0.1 ng/mL). Most
      patients approximating zero hPAD4 levels had PAD4 autoantibodies. In contrast,
      most of those with higher plasma hPAD4 levels did not have detectable PAD4
      autoantibodies. CONCLUSION: The combination of these sandwich ELISA methods may
      be a potentially beneficial clinical tool for diagnosing RA.

PMID- 22986905
TI  - Knowledge, attitudes and practices of caregivers in relation to oral health of
      preschool children.
AB  - OBJECTIVE: To assess the knowledge, attitudes and practices of caregivers in
      Kuwait in relation to the oral health of preschool children. SUBJECTS AND
      METHODS: Questionnaires with multiple-choice questions were distributed to 334
      caregivers of children under the age of 6 years attending vaccination centers in
      Kuwait. For each question, one of the multiple-choice answers was consistent with
      the consensus in the pediatric dental literature in relation to early childhood
      caries prevention, and was considered to be correct. The chi2 test, independent t
      test, ANOVA, and stepwise linear regression were used to assess the associations
      between the variables in question and p <= 0.05 was accepted as statistically
      significant. RESULTS: Of the 334 participants, 234 (70%) were between 20 and 40
      years of age with a high school diploma or higher degree and had between 2 and 5
      children. The mean knowledge score was 4.68 +/- 1.87, the mean attitude score was
      4.34 +/- 0.88 and the mean practice score was 2.45 +/- 0.99. Major weaknesses
      were reported in infant oral health-related concepts. Mothers had better
      knowledge than other caregivers (p < 0.001). Higher education was significantly
      associated with better knowledge (p = 0.003) and better practices (p = 0.017). In
      addition, knowledge, attitude and level of education were positively and
      significantly associated with practices (p < 0.005). CONCLUSIONS: Our study
      showed that caregivers had weak knowledge and practice in relation to the oral
      health of preschool children. Mothers and caregivers with higher education had
      better knowledge and practices. Education and attitude appeared to be favorable
      indicators of the caregivers' practices with regard to the oral health of their
      preschool children.

PMID- 22986903
TI  - Genome-wide study identifies two loci associated with lung function decline in
      mild to moderate COPD.
AB  - Accelerated lung function decline is a key COPD phenotype; however, its genetic
      control remains largely unknown. We performed a genome-wide association study
      using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation
      equations were used to assess genetic contributions to lung function decline over
      a 5-year period in 4,048 European American Lung Health Study participants with
      largely mild COPD. Genotype imputation was performed using reference HapMap II
      data. To validate regions meeting genome-wide significance, replication of top
      SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1)
      within the regions of interest were selected for tissue expression studies using
      immunohistochemistry. Two intergenic SNPs (rs10761570, rs7911302) on chromosome
      10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after
      Bonferroni. Further support for the chromosome 10 region was obtained by
      imputation, the most significantly associated imputed SNPs (rs10761571,
      rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results
      were not replicated in four general population cohorts or a smaller cohort of
      subjects with moderate to severe COPD; however, we show novel expression of genes
      near regions of significantly associated SNPS, including TMEM26 and FOXA1 in
      airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels
      of expression were associated with lung function and COPD status. We identified
      two novel regions associated with lung function decline in mild COPD. Genes
      within these regions were expressed in relevant lung cells and their expression
      related to airflow limitation suggesting they may represent novel candidate genes
      for COPD susceptibility.

PMID- 22986906
TI  - Distinct patterns and behaviour of urothelial carcinoma with respect to
      anatomical location: how molecular biomarkers can augment clinico-pathological
      predictors in upper urinary tract tumours.
AB  - PURPOSE: Upper urinary tract urothelial carcinoma (UTUC) shares many similarities
      with bladder-UC, but there is strong evidence on a clinical, aetiological,
      epidemiological and genetic level that key differences exist. In this review, we
      aim to highlight how UTUC differs from bladder-UC and report on the utility of
      molecular markers in the diagnosis and management of UTUC. MATERIALS AND METHODS:
      A systematic literature search was conducted using the Medline and Embase
      databases and specific keyword combinations: 'urothelial carcinoma', 'bladder
      cancer', 'transitional cell carcinoma', 'upper tract', 'upper urinary tract',
      'genetics', 'prognosis' and 'biomarkers'. RESULTS: UTUC has specific acquired
      (e.g. Balkans nephropathy, phenacetin abuse) and genetic hereditary non-polyposis
      colorectal cancer risk factors compared with bladder-UC. In general, the
      molecular biology of UC is broadly similar, irrespective of location in the
      urinary tract. However, there are distinct genetic (microsatellite instability)
      and epigenetic (hypermethylation) differences between some UTUC and bladder-UC.
      Clinical-pathological variables (e.g. hydronephrosis, tumour architecture, tumour
      location, stage and grade) have independent predictive power in UTUC, but tissue
      and urinary biomarkers can improve the clinical prediction of recurrence,
      invasion and survival in UTUC, though the evidence level is weak. CONCLUSIONS:
      UTUC shares many similarities with bladder-UC, but there is strong evidence that
      they should be considered as distinct urothelial entities. Prospective multi
      institutional studies investigating molecular markers are urgently needed to
      augment clinic-pathological predictors in UTUC.

PMID- 22986907
TI  - Predictive tools for clinical decision-making and counseling of patients with
      upper tract urothelial carcinoma.
AB  - BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare disease with a
      highly heterogeneous biologic behavior. Accurate individualized prediction of the
      behavior of UTUC could help guide personalized clinical decision-making regarding
      optimal therapy. METHODS: A MEDLINE literature search was performed on UTUC
      predictive tools. We recorded input variables, prediction form, number of
      patients used to develop the prediction tools, outcomes being predicted,
      prediction tool-specific features, predictive accuracy, and whether internal or
      external validations were performed. Each prediction tool was classified
      according to the clinical disease state it addressed and the outcome it
      predicted. RESULTS: The literature search generated five published tools for UTUC
      staging and prognostication. None of these prediction tools have undergone
      external validation yet. Two tools focused on the clinical decision-making
      regarding conservative management versus radical nephroureterectomy (RNU),
      lymphadenectomy versus not, and neoadjuvant systemic therapy versus not. Three
      tools focused on the prognosis after RNU, thereby helping in the decision-making
      regarding adjuvant systemic chemotherapy. CONCLUSIONS: Management of UTUC is
      challenging, and there are no high-level data to guide physicians and patients.
      Prognostic tools relying on data from large cohorts of patients are currently the
      best source of information for evidence-based management of UTUC patients.

PMID- 22986908
TI  - What is the optimal first-line agent in children requiring antihypertensive
      medication?
AB  - There has been an evolution in the understanding of the treatment of hypertension
      in children and adolescents over the past decade. This has been fueled in part by
      the increased attention paid to the clinical problem, given the increasing
      numbers of children and adolescents being diagnosed with this condition. There
      has also been a growing number of clinical trials performed and completed that
      demonstrate the blood pressure (BP)-lowering effects of antihypertensives and the
      side effect profiles of these medications, and that has led to FDA-labeling of
      many antihypertensive medications for use in children and adolescents. However,
      none of these trials has provided definitive data on the optimal first line agent
      for this patient population. Clinical experience and other approaches discussed
      in this review are still necessary to guide treatment of hypertension in the
      young. The quest for the optimal antihypertensive agent is just beginning, and it
      is going to take some extraordinary effort to reach that goal.

PMID- 22986909
TI  - Update on imaging for suspected renovascular hypertension in children and
      adolescents.
AB  - Although the epidemic of childhood obesity in the developed world has resulted in
      more children being diagnosed with primary hypertension, renovascular disease
      remains an important consideration. The reason for investigation is to try and
      delineate if renovascular disease is present, as there is the potential to treat
      this group of patients. Those patients are usually identified by poor blood
      pressure control, despite the use of multiple anti-hypertensive medications or
      having known associated syndromes. Although advances in Doppler renal
      ultrasonography, computed tomography angiography (CTA) and magnetic resonance
      angiography (MRA) have occurred over the last decade, digital subtraction
      angiography remains the gold standard investigation, and offers a possible
      therapeutic intervention at the same time.

PMID- 22986911
TI  - Artificial muscle for reanimation of the paralyzed face: durability and
      biocompatibility in a gerbil model.
AB  - BACKGROUND: Current management of permanent facial paralysis centers on nerve
      grafting and muscle transfer; however, limitations of those procedures call for
      other options. OBJECTIVES: To determine the durability and biocompatibility of
      implanted artificial muscle in a gerbil model and the degree of inflammation and
      fibrosis at the host tissue-artificial muscle interface. METHODS: Electroactive
      polymer artificial muscle (EPAM) devices engineered in medical-grade silicone
      were implanted subcutaneously in 13 gerbils. The implanted units were stimulated
      with 1 kV at 1 Hz, 24 h/d via a function generator. Electrical signal
      input/output was recorded up to 40 days after implantation. The animals were
      euthanized between 23 and 65 days after implantation, and the host tissue-implant
      interface was evaluated histologically. RESULTS: The animals tolerated
      implantation of the EPAM devices well, with no perioperative deaths. The muscle
      devices created motion for a mean of 30.3 days (range, 19-40 days), with a mean
      of 2.6 * 106 cycles (range, 1.6 * 106 to 3.5 * 106 cycles). Histologic
      examination of the explanted devices revealed the development of a minimal
      fibrous capsule surrounding the implants, with no evidence of bacterial infection
      or inflammatory infiltrate. No evidence of device compromise, corrosion, or
      silicone breakdown was noted. CONCLUSIONS: Artificial muscle implanted in this
      short-term animal model was safe and functional in this preliminary study. We
      believe that EPAM devices will be a safe and viable option for restoration of
      facial motions in patients with irreversible facial paralysis.

PMID- 22986910
TI  - Mechanisms and consequences of inflammatory signaling in the myocardium.
AB  - To further understand chronic heart disease, such as heart failure and
      cardiomyopathy, we must fully define signaling pathways within the myocardium.
      Recent studies suggest that some forms of heart disease are associated with a
      chronic low-grade inflammation that promotes adverse ventricular remodeling and
      correlates with disease progression. Several inflammatory mediators, including
      TNF-alpha, IL-1beta, and IL-6, are involved in cardiac injury subsequent to
      myocardial ischemia and reperfusion, sepsis, viral myocarditis, and transplant
      rejection. Once activated, components of the inflammatory response can have both
      beneficial and deleterious effects on the heart. In this review, we discuss the
      complex inflammatory signaling pathways in the myocardium and potential
      therapeutic implications.

PMID- 22986912
TI  - Addressing disparities in school readiness through promotion of parenting in well
      child care: the broader context of let's read.

PMID- 22986913
TI  - Dabigatran etexilate: another double-edged drug? : editorial to: "the beneficial
      effects of a direct thrombin inhibitor, dabigatran etexilate, on the development
      and stability of atherosclerotic lesions in apolipoprotein E-deficient mice" by
      N. Kadoglou et al.

PMID- 22986914
TI  - Challenges in intermetallics: synthesis, structural characterization, and
      transitions.
AB  - Intermetallics that contain rare-earth elements are particularly interesting
      because of their temperature- and pressure-dependent structural and physical
      transitions that make them potential candidates for magnetic applications. This
      article highlights synthetic routes and structural characterization advancements
      used to investigate intermetallic materials. Experimental and theoretical
      examples of three intermetallic structure types--ThCr(2)Si(2), Heusler and Laves-
      are discussed to present a historical review and to illustrate the grand
      challenges in unravelling structure-property relationships of intermetallic
      compounds.

PMID- 22986915
TI  - Public health action in genomics is now needed beyond newborn screening.
AB  - For decades, newborn screening was the only public health program in the US
      focused on reducing morbidity, mortality and disability in people affected by
      genetic conditions. The landscape has changed, however, as evidence-based
      recommendations are now available for several other genomic applications that can
      save lives now in the US. Many more such applications are expected to emerge in
      the next decade. An action plan, based on evidence, provides the impetus for a
      new paradigm for public health practice in genomics across the lifespan using
      established multilevel processes as a guide. These include policy interventions,
      education, clinical interventions, and surveillance. Applying what we know today
      in hereditary breast/ovarian cancer, Lynch syndrome and familial
      hypercholesterolemia has the potential to affect thousands of people in the US
      population every year. Enhanced partnerships between genetic and nongenetic
      providers of clinical medicine and public health are needed to overcome the
      challenges for implementing genomic medicine applications both now and in the
      future.

PMID- 22986916
TI  - Postprandial hyperglycemia corrected by IGF-I (Increlex(r)) in Laron syndrome.
AB  - BACKGROUND: Laron syndrome is caused by a mutation in the growth hormone (GH)
      receptor and manifests as insulin-like growth factor-I (IGF-I) deficiency, severe
      short stature, and early hypoglycemia. We report a case with postprandial
      hyperglycemia, an abnormality not reported previously. Postprandial hyperglycemia
      was due to chronic IGF-I deficiency, and was reversed by IGF-I replacement
      therapy. METHODS: A Moroccan girl referred for short stature at 7 years and 8
      months of age had dwarfism [height, 78 cm (-9 SDs); weight, 10 kg (-4 SDs)],
      hypoglycemia, and truncal obesity. Her serum IGF-I level was very low, and her
      baseline serum GH level was elevated to 47 mIU/l. Molecular analysis showed a
      homozygous mutation in the GH receptor gene. RESULTS: Continuous glucose
      monitoring before treatment showed asymptomatic hypoglycemia with postprandial
      hyperglycemia (2.5 g/l, 13.75 mmol/l). Treatment with recombinant human IGF-I
      (mecasermin, Increlex(r)) was started. The blood glucose profile improved with
      0.04 ug/kg/day and returned to normal with 0.12 ug/kg/day. CONCLUSION:
      Postprandial hyperglycemia is a metabolic consequence of chronic IGF-I
      deficiency. The beneficial effect of IGF-I replacement therapy may be ascribable
      to improved postprandial transfer of glucose.

PMID- 22986917
TI  - Sepsis: going to the heart of the matter.
AB  - Although myocardial depression is the predominant cause of death in severe
      sepsis/septic shock, it remains disputed whether the functional changes are a
      consequence of structural alterations. If we look at myocardial dysfunction from
      the perspective of a critically ill patient, there are a few questions to be
      asked: What causes myocardial dysfunction? What is the pathophysiology of cardiac
      dysfunction and death? Is there something that could be done to prevent the
      outcome? Each of these questions is interrelated and the answers will be more
      easily addressed if we continue to understand the basic mechanisms that are
      implicated. The principal mechanisms proposed for the pathogenesis of myocardial
      dysfunction support a prominent role for functional rather than anatomical
      abnormalities. However, attempts to reduce the high mortality in septic patients
      by manipulating the functional alterations have provided limited success. In
      recent years, the concept of septic cardiomyopathy has evolved, which implies
      alterations in the myocardial phenotype. This review includes an overview on the
      activation of the immune system and therapeutic approaches in sepsis, myocardial
      structural changes in the human septic heart, experimental models of sepsis, and
      cellular, molecular and functional myocardial changes seen in a variety of
      experimental sepsis models. The abnormal parameters discussed may emerge as
      therapeutic targets, for which modulation might provide beneficial effects on
      cardiovascular outcome and mortality in sepsis in the future.

PMID- 22986918
TI  - Association among ORMDL3 gene expression, 17q21 polymorphism and response to
      treatment with inhaled corticosteroids in children with asthma.
AB  - Recent genome-wide association studies linked childhood asthma with single
      nucleotide polymorphisms (SNPs) in ORM1-like protein 3 (ORMDL3) gene region on
      chromosome 17q21. We analyzed the effect of functional SNP rs2872507 in ORMDL3
      gene region on the response to antiasthmatic treatment with inhaled
      corticosteroids (ICSs) and ORMDL3 gene expression. Forced expiratory volume in 1
      s increased significantly by 13.3% of predicted value after therapy in atopic
      asthmatics with AA genotype, compared with 7.0% in heterozygotes and 4.9%
      increase in GG homozygotes (P=0.0176). Median relative expression of ORMDL3 gene
      in asthmatics with AA, AG and GG genotypes was 0.75, 1.05 and 1.21, respectively
      (P<0.0001). Treatment with ICSs was significantly associated with the increase of
      median relative expression of ORMDL3 gene, from 0.88 to 1.21 (P=0.0032) in atopic
      asthmatics. Our results suggest that rs2872507 is associated with ORMDL3 gene
      expression and with ICS treatment response in children with atopic asthma. 

PMID- 22986919
TI  - Highly stereoselective modifications of peptides via Pd-catalyzed allylic
      alkylation of internal peptide amide enolates.
AB  - Pd-catalyzed allylations are excellent tools for stereoselective peptide
      modifications, showing several advantages compared to normal alkylations.
      Reactions of internal peptide amide enolates with Pd-allyl complexes proceed not
      only with high yields of up to 86%, they show also high regio- and
      diastereoselectivities (88-99%), giving rise to the trans-configured products.
      Therefore, this protocol is a powerful synthetic tool for the synthesis of
      natural product and drug molecules.

PMID- 22986920
TI  - Linagliptin increases incretin levels, lowers glucagon, and improves glycemic
      control in type 2 diabetes mellitus.
AB  - INTRODUCTION: Linagliptin is a xanthine-based dipeptidyl peptidase (DPP)-4
      inhibitor that is now available in numerous countries worldwide for the treatment
      of type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate further
      the mechanisms underlying the improvements in glycemic control observed with
      linagliptin. The effects of linagliptin on DPP-4, pharmacodynamic parameters, and
      glycemic control versus placebo were assessed in patients with inadequately
      controlled T2DM. METHODS: Patients in this phase 2a, multicenter, randomized,
      double-blind, placebo-controlled study received placebo (n = 40) or linagliptin 5
      mg (n = 40). Sitagliptin 100 mg (n = 41) once daily for 4 weeks was included for
      exploratory purposes. Primary endpoints for linagliptin versus placebo: change
      from baseline to day 28 in 24-h weighted mean glucose (WMG) and intact glucagon
      like peptide (GLP)-1 area under the time-effect curve between 0 and 2 h (AUEC(0
      2h)) following meal tolerance test on day 28. RESULTS: Linagliptin increased
      intact GLP-1 AUEC(0-2h) (+18.1 pmol/h/L) and lowered 24-h WMG (-1.1 mmol/L)
      versus placebo (both P < 0.0001) after 28 days. Intact glucose-dependent
      insulinotropic polypeptide increased in line with GLP-1 (+91.4 pmol/h/L increase
      vs. placebo; P < 0.0001). Glycated hemoglobin (-0.22%; P = 0.0021), fasting
      plasma glucose (-0.6 mmol/L; P = 0.0283), and glucose (AUEC(0-3h)) (-5.9
      mmol/h/L; P < 0.0001) improved significantly with linagliptin versus placebo.
      Most adverse events were mild; hypoglycemia or serious adverse events were not
      reported. Sustained DPP-4 inhibition (>=80%) throughout the treatment period was
      accompanied by significant reductions in glucagon starting at day 1 of
      linagliptin administration. CONCLUSION: Linagliptin was well tolerated and
      effectively inhibited plasma DPP-4 activity in patients with T2DM, producing
      immediate improvements in incretin levels, glucagon suppression, and glycemic
      control that were maintained throughout the study period.

PMID- 22986921
TI  - Differential localisation of BPIFA1 (SPLUNC1) and BPIFB1 (LPLUNC1) in the nasal
      and oral cavities of mice.
AB  - Despite being initially identified in mice, little is known about the sites of
      production of members of the BPI fold (BPIF) containing (PLUNC) family of
      putative innate defence proteins in this species. These proteins have largely
      been considered to be specificaly expressed in the respiratory tract, and we have
      recently shown that they exhibit differential expression in the epithelium of the
      proximal airways. In this study, we have used species-specific antibodies to
      systematically localize two members of this protein family; BPIFA1
      (PLUNC/SPLUNC1) and BPIFB1 (LPLUNC1) in adult mice. In general, these proteins
      exhibit distinct and only partially overlapping localization. BPIFA1 is highly
      expressed in the respiratory epithelium and Bowman's glands of the nasal
      passages, whereas BPIFB1 is present in small subset of goblet cells in the nasal
      passage and pharynx. BPIFB1 is also present in the serous glands in the proximal
      tongue where is co-localised with the salivary gland specific family member,
      BPIFA2E (parotid secretory protein) and also in glands of the soft palate. Both
      proteins exhibit limited expression outside of these regions. These results are
      consistent with the localization of the proteins seen in man. Knowledge of the
      complex expression patterns of BPIF proteins in these regions will allow the use
      of tractable mouse models of disease to dissect their function.

PMID- 22986922
TI  - Biological activity and safety of Tripterygium extract prepared by sodium
      carbonate extraction.
AB  - The commercial preparation named "Tripterygium glycosides" prepared by column
      chromatography has been used for the treatment of inflammatory and autoimmune
      diseases with significant efficacy but concurrent toxicity. The aim of this study
      was to reduce the toxicity of Tripterygium extracts, using cytotoxicity and anti
      inflammatory activity of the three principal active components of Tripterygium
      wilfordii Hook. F. (TWHF)as guiding parameters. Column chromatography was
      replaced by sodium carbonate extraction for removing the acidic compounds and
      enriching epoxyditerpenoids and alkaloids in the extract. Results showed that the
      therapeutic index (IC50/EC50) on murine macrophage Raw 264.7 cells and rat
      mesangial HBZY-1 cells of the extract prepared by sodium carbonate extraction was
      significantly higher than that of Tripterygium glycosides(0.8 and 5.2 vs. 0.3 and
      2.6, p < 0.05), while its cytotoxicity on human liver HL7702 cells was
      significantly lower (14.5 +/- 1.4 vs. 6.8 +/- 0.9, p < 0.05). Further acute oral
      toxicity experiments showed that the LD50 value of this extract was 1,210 mg/kg
      compared to 257 mg/kg for Tripterygium glycosides. All the above results suggest
      that Tripterygium extract prepared by sodium carbonate extraction may represent a
      potentially optimal source of medicine with good therapeutic index.

PMID- 22986924
TI  - Proximate composition, nutritional attributes and mineral composition of
      Peperomia pellucida L. (Ketumpangan Air) grown in Malaysia.
AB  - This study presents the proximate and mineral composition of Peperomia pellucida
      L., an underexploited weed plant in Malaysia. Proximate analysis was performed
      using standard AOAC methods and mineral contents were determined using atomic
      absorption spectrometry. The results indicated Peperomia pellucida to be rich in
      crude protein, carbohydrate and total ash contents. The high amount of total ash
      (31.22%)suggests a high-value mineral composition comprising potassium, calcium
      and iron as the main elements. The present study inferred that Peperomia
      pellucida would serve as a good source of protein and energy as well as
      micronutrients in the form of a leafy vegetable for human consumption.

PMID- 22986923
TI  - Effects of sorghum [Sorghum bicolor (L.) Moench] crude extracts on starch
      digestibility, Estimated Glycemic Index (EGI), and Resistant Starch (Rs) contents
      of porridges.
AB  - Bran extracts (70% aqueous acetone) of specialty sorghum varieties (tannin,
      black, and black with tannin) were used to investigate the effects of sorghum
      phenolic compounds on starch digestibility, Estimated Glycemic Index (EGI), and
      Resistant Starch (RS) of porridges made with normal corn starch, enzyme resistant
      high amylose corn starch, and ground whole sorghum flours. Porridges were cooked
      with bran extracts in a Rapid Visco-analyser (RVA). The cooking trials indicated
      that bran extracts of phenolic-rich sorghum varieties significantly reduced EGI,
      and increased RS contents of porridges. Thus, there could be potential health
      benefits associated with the incorporation of phenolic-rich sorghum bran extracts
      into foods to slow starch digestion and increase RS content.

PMID- 22986925
TI  - The correlation between age, body weight and testicular parameters in Murrah
      buffalo bulls raised in Brazil.
AB  - Buffalo are an economically important source for meat and milk production,
      especially in Brazil. However, important aspects of their biology remain unknown
      thus far. Herein, we describe the reproductive characteristics of male Murrah
      buffalo (Bubalus bubalis) raised under extensive management conditions by
      applying biometrics associated with testicular weight. We analyzed seven males,
      divided into two groups: G1, which consisted of four 18-month-old animals, and
      G2, which consisted of three 24-month-old animals. Testicular development occurs
      slowly in Murrah buffalo, suggesting a delay of sexual maturity. The biometric
      testicular parameters analyzed were scrotal circumference, testicular weight,
      testicular length, testicular width, testicular thickness and testicular
      circumference. Our data indicate strong correlations between SC, age and body
      weight, and additional significant relationships were identified between body
      weight, age and other testicular parameters. Thus, these parameters are suitable
      indicators when selecting bulls for breeding purposes.

PMID- 22986926
TI  - Oxidative stress produced by xanthine oxidase induces apoptosis in human
      extravillous trophoblast cells.
AB  - Oxidative stress has been recognized as an important factor in the
      pathophysiology of preeclampsia. It has been reported that the expression of
      xanthine oxidase (XO) in the cytotrophoblast and plasma hydrogen peroxide
      (H(2)O(2)) level are significantly higher in preeclamptics than in control women.
      The aim of this study was to clarify the biological influence of reactive oxygen
      species (ROS) produced by XO on extravillous trophoblast (EVT) cells. TCL1 cells,
      a human immortalized EVT cell line, were incubated with xanthine and XO (X/XO).
      We then measured the cell number, urate level of the culture media and the
      apoptotic cell ratio. Similar experiments were performed with additional
      administration of allopurinol, catalase, L-NAME or D-NAME, and with
      administration of H(2)O(2) in substitution for X/XO. We assessed the effects of
      H(2)O(2) on invasion ability, tube-like formation and protein expression of HIF1A
      and ITGAV of TCL1. Finally, the apoptotic cell ratio using primary cultured
      trophoblasts was measured following exposure to H(2)O(2). X/XO decreased the
      relative cell number and increased the urate level and apoptotic cell ratio
      significantly. Elevation of the urate level and apoptotic cell ratio was
      attenuated by allopurinol and catalase, respectively. L-NAME and D-NAME had no
      influence on these effects. H(2)O(2) also decreased the relative cell number.
      Pretreatment with H(2)O(2) significantly inhibited the invasion ability, tube
      like formation and HIF1A and ITGAV of TCL1. H(2)O(2) also induced apoptosis in
      primary cultured trophoblasts. In conclusion, ROS produced by XO induced
      apoptosis and affected EVT function including invasion and differentiation.

PMID- 22986927
TI  - Interrelationships between apoptosis and fertility in bull sperm.
AB  - Male fertility, the ability of sperm to fertilize and activate the egg and
      support early embryogenesis, is vital for mammalian reproduction. Despite
      producing adequate numbers of sperm with normal motility and morphology, some
      males suffer from low fertility whose molecular mechanisms are not known. The
      objective was to determine apoptosis in sperm from high and low fertility bulls
      and its relationship with male fertility. DNA damage, phosphatidylserine (PS)
      translocation, and expression of pro- and anti-apoptotic proteins (BAX and BCL-2)
      in the sperm were determined using TUNEL, Annexin V, and immunoblotting
      approaches, respectively. Amounts of apoptotic spermatozoa were 2.86 (+/- 1.31)
      and 3.00 (+/- 0.96) in high and low fertility bulls, respectively (P=0.548), and
      were not correlated with fertility. There was a negative correlation between
      early necrotic spermatozoa and viable spermatozoa (r = -0.99, P<0.0001).
      Fertility scores were correlated with live spermatozoa detected by eosin-nigrosin
      test and necrotic spermatozoa determined via flow cytometry (r = -0.49, P<0.006
      and r = -0.266, P<0.0113, respectively). BAX level was higher in low fertile
      group than high fertile group; however, this difference was not statistically
      significant due to the variations of bull samples (Bull 1-3 vs. Bull 4-5) in low
      fertile group (P<0.283). BCL-2 was not detectable in any of the sperm samples.
      The results shed light onto molecular and cellular underpinnings of male
      fertility.

PMID- 22986928
TI  - Characterization of a human apolipoprotein a-I construct expressed in a bacterial
      system.
AB  - Apolipoprotein A-I (apoA-I) is the major protein component of high density
      lipoproteins. This protein has key functions in lipoprotein metabolism and its
      plasma concentration is inversely correlated with the incidence of
      atherosclerosis and cardiovascular diseases. There is an increasing need to
      develop methods for efficient production of recombinant apoA-I for using it in
      basic research or pharmacological therapy. An apoA-I variant lacking two amino
      acid residues at the N-terminus can be easily produced by bacterial expression.
      We report here the characterization of this variant comparing its properties with
      those of the protein isolated from human serum. The results validate the use of
      this variant in future assays and investigations.

PMID- 22986929
TI  - A review of recent developments in image-guided radiation therapy in cervix
      cancer.
AB  - Brachytherapy is an essential part of radiotherapy treatment for cervical cancer.
      Over the decades, it has evolved from manual loading of radium and caesium to
      remote after-loaders and from low-dose and medium-dose rates to high-dose rates.
      Over the past 10 years, 3D image-based Brachytherapy has evolved and established
      itself as the gold standard, improving local control and overall survival, and
      significantly reducing toxicity. In this article, we review some of the available
      literature on gynaecologic brachytherapy, more specifically on topics such as
      dose rates, high-dose-rate/pulsed-dose-rate (HDR/PDR) brachytherapy and image
      based brachytherapy (IBBT), and present some of the evidence that establishes
      IBBT.

PMID- 22986930
TI  - No dose-dependent increase in fracture risk after long-term exposure to high
      doses of retinol or beta-carotene.
AB  - Uncertainty remains over whether or not high intakes of retinol or vitamin A
      consumed through food or supplements may increase fracture risk. This
      intervention study found no increase in fracture risk among 2,322 adults who took
      a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for
      as long as 16 years. There was some evidence that beta-carotene supplementation
      decreased fracture risk in men. INTRODUCTION: There is conflicting
      epidemiological evidence regarding high intakes of dietary or supplemental
      retinol and an increased risk for bone fracture. We examined fracture risk in a
      study administering high doses of retinol and beta-carotene (BC) between 1990 and
      2007. METHODS: The Vitamin A Program was designed to test the efficacy of retinol
      and BC supplements in preventing malignancies in persons previously exposed to
      blue asbestos. Participants were initially randomised to 7.5 mg retinol
      equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from
      1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures
      were identified by questionnaire and hospital admission data up until 2006. Risk
      of any fracture or osteoporotic fracture according to cumulative dose of retinol
      and BC supplementation was examined using conditional logistic regression models
      adjusting for age, sex, smoking, body mass index, medication use and previous
      fracture. RESULTS: Supplementation periods ranged from 1 to 16 years. Of the
      2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures.
      No associations were observed between cumulative dose of retinol and risk for any
      fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR
      per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was
      associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI
      0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97).
      CONCLUSIONS: This study observed no increases in fracture risk after long-term
      supplementation with high doses of retinol and/or beta-carotene.

PMID- 22986931
TI  - The use of deep frozen and irradiated bone allografts in the reconstruction of
      tibial plateau fractures.
AB  - To investigate the clinical behavior of deep frozen and irradiated bone
      allografts in the treatment of depressed tibial plateau fractures. Twenty-two
      patients with a tibial plateau fracture were treated with cancellous bone
      allografts. The bone allograft preparation process included fresh-freezing at -70
      degrees C for 4 weeks and gamma-irradiation at 25 kGy. All of the patients were
      followed for 1-2 years. The clinical effects were assessed using the Rasmussen
      score for tibial head fractures and X-rays. Postoperatively, the average
      excellent and fair Rasmussen scores were 88.9%. Only one patient developed an
      infection, with no integration between allograft and recipient bone observed. All
      of the other bone allografts were incorporated successfully, and no osteoporosis
      or sclerosis was observed. The frozen and gamma-irradiated bone allograft is a
      good alternative in the treatment of tibial plateau fractures, which we have
      shown can integrate with the surrounding host bone.

PMID- 22986932
TI  - Risk factors for anastomotic leakage after anterior resection for rectal cancer.
AB  - BACKGROUND: The risk factors for anastomotic leak (AL) after anterior resection
      have been evaluated in several studies and remain controversial as the findings
      are often inconsistent or inconclusive. OBJECTIVE: To analyze the risk factors
      for AL after anterior resection in patients with rectal cancer. DESIGN:
      Retrospective analysis. SETTING: The Nationwide Inpatient Sample 2006 to 2009.
      PATIENTS: A total of 72 055 patients with rectal cancer who underwent elective
      anterior resection. MAIN OUTCOME MEASURES: To build a predictive model for AL
      using demographic characteristics and preadmission comorbidities, the lasso
      algorithm for logistic regression was used to select variables most predictive of
      AL. RESULTS: The AL rate was 13.68%. The AL group had higher mortality vs the non
      AL group (1.78% vs 0.74%). Hospital length of stay and cost were significantly
      higher in the AL group. Laparoscopic and open resections with a diverting stoma
      had a higher incidence of AL than those without a stoma (15.97% vs 13.25%).
      Multivariate analysis revealed that weight loss and malnutrition, fluid and
      electrolyte disorders, male sex, and stoma placement were associated with a
      higher risk of AL. The use of laparoscopy was associated with a lower risk of AL.
      Postoperative ileus, wound infection, respiratory/renal failure, urinary tract
      infection, pneumonia, deep vein thrombosis, and myocardial infarction were
      independently associated with AL. CONCLUSIONS: Anastomotic leak after anterior
      resection increased mortality rates and health care costs. Weight loss and
      malnutrition, fluid and electrolyte disorders, male sex, and stoma placement
      independently increased the risk of leak. Laparoscopy independently decreased the
      risk of leak. Further studies are needed to delineate the significance of these
      findings.

PMID- 22986937
TI  - Endonasal placement of spreader grafts: experience in 41 consecutive patients.
AB  - OBJECTIVES To evaluate the efficacy of placing spreader grafts via an endonasal
      approach and to examine the immediate and long-term functional results. METHODS A
      retrospective review was performed of 41 consecutive cases involving adult
      patients who underwent nasal valve reconstruction. Medical history and clinical
      examination established the cause of nasal obstruction, with internal valve
      dysfunction confirmed through endoscopic evaluation and the modified Cottle
      maneuver. Surgical correction involved a spreader graft harvested from autologous
      cartilage and placed endonasally. Comparison and evaluation of preoperative vs
      postoperative symptom severity, photographs, and patient self-assessment were
      used to quantify the results of the operation. RESULTS Our study included 22
      women and 19 men with a mean age (range) of 32 (19-56) years. Twenty-seven
      patients (66%) were Asian, 12 (29%) were white, and 2 (5%) were Hispanic. Thirty
      of 41 patients (73%) expressed strong concern regarding the presence of a
      transcolumellar scar. Among our patients with confirmed internal nasal valve
      dysfunction, 25 (61%) reported significant improvement, 15 (37%) noted some
      improvement, and 1 (2%) described no change; none reported a worsening of
      symptoms. CONCLUSIONS The endonasal approach to placement of spreader grafts for
      nasal valve reconstruction is effective at relieving nasal obstruction due to
      internal nasal valve dysfunction. Paramount to the success of the procedure is
      appropriate patient selection and careful attention to surgical technique.

PMID- 22986936
TI  - Reconstruction of nasal alar defects in asian patients.
AB  - OBJECTIVES: To present the aesthetic and functional outcomes of nasal alar
      reconstruction in Asian patients and to propose a working surgical algorithm.
      METHODS: Seventeen patients underwent nasal alar reconstruction at a university
      based facial plastic surgery practice from March 1, 1998, through February 28,
      2010. The male-female ratio was 10:7, with a median age of 59 years (range, 34-78
      years), and the mean follow-up duration was 64 months. RESULTS: The defect was
      mostly caused by basal cell carcinoma resection (14 of 17 [82%]), followed by the
      resection of squamous cell carcinoma, trauma, and excision of a previous scar.
      The mean defect size was 1.71 cm (range, 1-4 cm). The full-thickness defects were
      noted for 8 patients, whereas 9 had partial-thickness defects. The choice of
      reconstruction method was primarily based on the size and depth of the surgical
      defect. Most of the defects 1 to 2 cm in diameter needed nasolabial flaps (10 of
      17 [59%]), whereas full-thickness defects larger than 2 cm needed forehead flaps
      (3 of 17 [18%]) to reconstruct the external defect. Smaller defects less than 1
      cm were reconstructed with composite grafts (2 of 17 [12%]), a bilobed flap (1 of
      17 [6%]), or primary closure (1 of 17 [6%]). Seven of 8 full-thickness defects
      had the internal nasal lining reconstructed using a septal mucoperichondrial
      flap, and 1 case was reconstructed using a cutaneous turn-in flap. Reinforcement
      cartilage graft was used in 8 patients. No flap failure occurred except in 1
      case, in which necrosis of the internal lining flap caused contraction of the
      external flap with resultant alar rim elevation. An elevation of the alar margin
      and alar groove blunting occurred in 3 cases. No functional problems emerged.
      Subjective surgical outcome on a 4-point satisfaction scale revealed that 5
      patients (29%) were much satisfied, 10 patients (59%) were satisfied, 1 patient
      (6%) was fairly satisfied, and 1 patient (6%) was dissatisfied. CONCLUSIONS: The
      choice of reconstruction method of nasal alar defect in Asian patients depends
      primarily on the size and depth of the defect. Staged local flaps, use of
      cartilage reinforcement grafts, and internal lining reconstruction using septal
      mucoperichondrial flaps are key elements for achieving optimal aesthetic and
      functional results.

PMID- 22986938
TI  - Versatile applications of the polydioxanone plate in rhinoplasty and septal
      surgery.
AB  - BACKGROUND: Rhinoplasty and septal surgery often require the use of cartilage
      grafts. Autologous cartilage may be thin or deviated, and the use of an
      absorbable scaffold material to support the reimplanted cartilage during healing
      can improve technique and outcomes. OBJECTIVE: To describe the use of a
      polydioxanone plate not only as a template in extracorporeal septoplasty but also
      for various other grafts commonly used in rhinoplasty and for the repair of
      septal perforations. METHODS: A retrospective case note review was performed
      between November 1, 2007, and February 28, 2011, for all patients treated using a
      polydioxanone plate. Surgical outcomes are discussed. RESULTS: A polydioxanone
      plate was used in septal and/or rhinoplasty surgery in 102 patients treated
      during a 40-month period. Follow-up was 9 to 18 months (mean, 12 months), with 96
      patients reporting a good cosmetic or functional result. Up to 15% of patients
      experienced temporary septal swelling, but there were only 2 postoperative
      infections and no other significant complications. CONCLUSIONS: The polydioxanone
      plate is a safe and reliable absorbable implant that has many different
      applications in rhinoplasty and septal surgery. It not only acts as a scaffold
      but also stimulates and guides cartilage regeneration.

PMID- 22986939
TI  - Reformatted computed tomography to assess the internal nasal valve and
      association with physical examination.
AB  - OBJECTIVES: To assess the cross-sectional area and angle of the internal nasal
      valve more accurately by reformatting computed tomography (CT) scans of the nasal
      airway according to a more appropriate orientation than scans traditionally
      sectioned in the coronal plane and then to compare the results with clinical data
      on the nasal valve obtained from physical examination. METHODS: We performed a
      retrospective review of the medical records of 24 rhinoplasty patients treated at
      a private practice facial plastic surgery office affiliated with a tertiary care
      university hospital. The patients had fine-cut (0.75-mm section) CT scans ordered
      for nasal airway obstruction or nasal valve compromise at the same institution.
      These patients were evaluated from January 1, 2000, through December 31, 2010.
      The previously acquired CT scans were reformatted to obtain sections through the
      internal nasal valve at a more appropriate orientation. The internal nasal valve
      cross-sectional area and valve angle were measured through a standardized section
      (1 cut immediately anterior to the head of the inferior turbinate) from the
      reformatted scans. The cross-sectional area was also measured through the same
      point on the traditionally oriented CT scan, and the values were compared. The
      results from each patient's scan were compared with data from the patient's
      medical record and analyzed against the patient's preoperative modified Cottle
      examination findings. RESULTS: The CT scans oriented in the reformatted plane
      through the internal nasal valve provided a narrower valve angle than the
      traditionally oriented CT scans and more closely approximated the hypothesized
      true value of the internal nasal valve of 10 degrees  to 15 degrees  (P < .001).
      In a comparison of the same-side internal nasal valve angle and cross-sectional
      nasal valve area between the 2 different CT scan orientations, a statistically
      significant difference in the internal nasal valve angles between the 2 scan
      orientations was discovered, but this finding did not reach significance when
      distinguishing the nasal valve cross-sectional area. Finally, no correlation was
      found with regard to the preoperative modified Cottle maneuver scores for the
      internal nasal valve angle and cross-sectional valve area values in either scan
      orientation. CONCLUSIONS: Precise preoperative evaluation of the internal nasal
      valve is critical to the workup for reconstruction or repair of problems that
      involve this area. Although tools such as acoustic rhinometry exist to evaluate
      the cross-sectional area of the nasal valve, many rhinoplasty surgeons do not
      have access to this expensive equipment. A CT scan with reformatting in the
      proper plane of the internal nasal valve can provide the surgeon with improved
      anatomical information to assess that region. With this in mind, however, the
      surgeon should always perform a thorough preoperative physical examination and
      treat the patient and his or her symptoms, not the imaging studies, when
      considering a candidate for a surgical intervention.

PMID- 22986940
TI  - A review of 13 years of experience with endoscopic forehead-lift.
AB  - OBJECTIVE: To conduct objective quantitative and qualitative evaluations of the
      long-term result in endoscopic forehead-lift. METHODS: Medical charts of 143
      patients who underwent endoscopic forehead-lift between 1994 and 2007 were
      reviewed for postoperative complications and the duration of complaints. Patients
      received a questionnaire to evaluate satisfaction and social restriction after
      surgery. Objective photographic preoperative and postoperative eyebrow-to-eye
      distances in a relaxed position and during muscle contractions were obtained.
      RESULTS: A total of 98 patients (69% response; mean follow-up, 38 months) showed
      high satisfaction (score, 7.1 of 10). In a relaxed position, mean midpupil-to
      eyebrow elevation was 5.6 mm after surgery, with significant eyebrow symmetry
      between the left and right eyes (P < .05), and showed significant influence of
      time (P = .005) on persisting eyebrow elevation, with a decrease of almost 1 mm
      per year. Measurements during muscle contraction showed no relevant differences.
      CONCLUSION: Endoscopic forehead-lift enables long-lasting results with highly
      satisfied patients.

PMID- 22986941
TI  - Double-opposing rotation-advancement flaps for closure of forehead defects.
AB  - OBJECTIVE: To describe a local flap for closure of forehead defects of all sizes
      that does not alter the brow position or hairline. METHODS: Retrospective review
      of 16 cases in which the double-opposing rotation-advancement flaps were used for
      closure of small (<10 cm2), medium (10-20 cm2), and large (>20 cm2) forehead
      defects. This technique was developed from Orticochea's method for closure of
      large scalp wounds. RESULTS: All 16 patients underwent single-stage closure of
      forehead defects using our design. Six patients were men, 8 were women (mean age,
      71 years). Preoperative defect sizes ranged from 3 to 30 cm2 (mean, 18 cm2). All
      wounds resulted from Mohs surgery for cutaneous malignant neoplasms; 2 were
      adjacent to previous reconstructions. No recurrence of tumor was seen during the
      study period. No permanent frontal branch injuries occurred. One patient
      developed a moderate cellulitis. Photographic analysis showed that brow position
      and hairline contour were maintained in all cases. CONCLUSIONS: The double
      opposing rotation-advancement flap closure is a versatile reconstructive option
      for small, medium, and large forehead defects. The technique involves elevation
      of opposing, asymmetric flaps, with subsequent rotation of one side and
      advancement of the contralateral side. Single-stage closure may be accomplished
      without unappealing changes to the brow position or hairline.

PMID- 22986942
TI  - Split hump technique for reduction of the overprojected nasal dorsum: a
      statistical analysis on subjective body image in relation to nasal appearance and
      nasal patency in 97 patients undergoing aesthetic rhinoplasty.
AB  - OBJECTIVES: To describe the split hump technique (SHT) and to examine its
      effectiveness for correction of an overprojected nasal dorsum in patients
      undergoing aesthetic rhinoplasty. METHODS: This prospective study included 97
      patients. Objective assessment was performed using a short, practical
      questionnaire. Investigation focused on nasal patency and the patient perception
      of body image in relation to nasal appearance using 5-point Likert scale
      questions and visual analog scales. RESULTS: Use of the SHT resulted in a
      significant improvement in nasal patency and aesthetic nasal perception. Sum
      functional question scores decreased from 9.154 to 6.351 and aesthetic question
      scores from 13.897 to 6.825 (P < .001 for both). Mean aesthetic visual analog
      scale scores improved in all patients, from 3.346 to 7.782 (P < .001). Graphic
      illustration of this improvement revealed a gaussian curve of normal distribution
      around a mean (SD) improvement of 4.48 (1.93). CONCLUSIONS: Traditional en bloc
      humpectomy maneuvers are frequently combined with spreader graft use to avoid
      postoperative inferomedial repositioning of the upper lateral cartilages and
      inverted-V deformity. The SHT for correction of the overprojected dorsum creates
      a paradigm change in this patient group. The transverse segments of the upper
      lateral cartilages are saved and repositioned instead of being resected as a part
      of an en bloc osseocartilaginous composite hump resection in a transverse plane.
      Several modifications of the SHT enable the surgeon to deproject the nose while
      keeping sufficient strength in the keystone area and augmenting dorsal width.
      Using statistical analysis of subjective patient data, we could prove a broad
      acceptance and appreciation for the SHT.

PMID- 22986943
TI  - The hyoplatysmal ligament: characterization and biomechanical properties.

PMID- 22986946
TI  - Titian's Portrait of a Man Holding a Book.

PMID- 22986947
TI  - Purinergic receptor antagonist A438079 protects against acetaminophen-induced
      liver injury by inhibiting p450 isoenzymes, not by inflammasome activation.
AB  - Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure
      in the western world. Controversy exists regarding the hypothesis that the
      hepatocyte injury is amplified by a sterile inflammatory response, rather than
      being the result of intracellular mechanisms alone. A recent study suggested that
      the purinergic receptor antagonist A438079 protects against APAP-induced liver
      injury by preventing the activation of the Nalp3 inflammasome in Kupffer cells
      and thereby preventing inflammatory injury. To test the hypothesis that A438079
      actually affects the intracellular signaling events in hepatocytes, C57Bl/6 mice
      were treated with APAP (300 mg/kg) and A438079 (80 mg/kg) or saline and GSH
      depletion, protein adduct formation, c-jun-N-terminal kinase (JNK) activation,
      oxidant stress, and liver cell necrosis were determined between 0 and 6 h after
      APAP administration. APAP caused rapid GSH depletion, extensive protein adduct
      formation in liver homogenates and in mitochondria, JNK phosphorylation and
      mitochondrial translocation of phospho-JNK within 2 h, oxidant stress, and
      extensive centrilobular necrosis at 6 h. A438079 significantly attenuated GSH
      depletion, which resulted in a 50% reduction of total liver and mitochondrial
      protein adducts and substantial reduction of JNK activation, mitochondrial P-JNK
      translocation, oxidant stress, and liver injury. The same results were obtained
      using primary mouse hepatocytes. A438079 did not directly affect JNK activation
      induced by tert-butyl hydroperoxide and GSH depletion. However, A438079 dose
      dependently inhibited hepatic P450 enzyme activity. Thus, the protective effect
      of A438079 against APAP hepatotoxicity in vivo can be explained by its effect on
      metabolic activation and cell death pathways in hepatocytes without involvement
      of the Nalp3 inflammasome.

PMID- 22986948
TI  - Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral
      and oxidative stress effects: are they mediated by analogous mechanisms of
      action?
AB  - Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative
      damage. Little is known about the relationship between behavioral deficits and
      oxidative stress within the context of such exposures. Accordingly, the first
      experiment was carried out to address this issue. Male Wistar rats were
      administered 250 mg/kg of chlorpyrifos (CPF), 1.5 mg/kg of
      diisopropylphosphorofluoridate (DFP), or 15 mg/kg of parathion (PTN). Spatial
      learning in the water maze task was evaluated, and F(2)-isoprostanes (F(2)-IsoPs)
      and prostaglandin (PGE(2)) were analyzed in the hippocampus. A second experiment
      was designed to determine the degree of inhibition of brain acetylcholinesterase
      (AChE) activity, both the soluble and particulate forms of the enzyme, and to
      assess changes in AChE gene expression given evidence on alternative splicing of
      the gene in response to OP exposures. In addition, brain acylpeptide hydrolase
      (APH) activity was evaluated as a second target for OP-mediated effects. In both
      experiments, rats were sacrificed at various points to determine the time course
      of OPs toxicity in relation to their mechanism of action. Results from the first
      experiment suggest cognitive and emotional deficits after OPs exposure, which
      could be due to, at least in part, increased F(2)-IsoPs levels. Results from the
      second experiment revealed inhibition of brain AChE and APH activity at various
      time points post OP exposure. In addition, we observed increased brain read
      through splice variant AChE (AChE-R) mRNA levels after 48 h PTN exposure. In
      conclusion, this study provides novel data on the relationship between cognitive
      alterations and oxidative stress, and the diverse mechanisms of action along a
      temporal axis in response to OP exposures in the rat.

PMID- 22986952
TI  - The quality of 5-aminolevulinic acid-induced photodynamic diagnosis and
      transurethral resection of bladder tumors: does the urologist play a role?.
AB  - INTRODUCTION: The aim of this study is to evaluate the quality of photodynamic
      diagnosis (PDD) and transurethral resection of bladder tumors (TURBT) among
      different urologists. PATIENTS AND METHODS: The selected data consists of 194
      patients, 268 5-aminolevulinic acid (5-ALA)-induced PDD procedures and 934
      biopsies. Tumors were resected and biopsies were taken from suspicious areas
      under guidance of white light endoscopy and 5-ALA-induced fluorescence
      cystoscopy. The quality of PDD was determined by evaluating the mean number of
      tumors resected by 5 urologists and, thereafter, assessing the time to recurrence
      between groups. RESULTS: Urologist 1 took 37% more biopsies (p < 0.001) and
      diagnosed 42% more tumors (p = 0.005) and 46% more false positives (p < 0.001)
      from bladders compared to urologists 2, 3, 4 and 5 together. The mean time to
      bladder cancer recurrence for all recurrences within 0-18 months was 11.0 months
      for operator 1 and 8.3 months for the other urologists (p = 0.01). CONCLUSIONS:
      The resecting urologist appears to be an important factor for the quality of
      standard and PDD-assisted TURBT. Learning curve programs may be required with
      experienced surgeons accompanying those with less experience.

PMID- 22986950
TI  - The antioxidant role of paraoxonase 1 and vitamin E in three autoimmune diseases.
AB  - PURPOSE OF THE STUDY: To investigate the role of paraoxonase 1 (PON1) and vitamin
      E in the pathogenesis of some autoimmune diseases, and to correlate their levels
      with the disease activity. PROCEDURES: This randomized case control study was
      performed on 60 subjects: 45 patients [suffering from psoriasis, vitiligo and
      alopecia areata (AA) 15 patients each group] and 15 healthy controls. Venous
      blood and tissue biopsy were collected from each subject to estimate the levels
      of vitamin E and PON1. RESULTS: All patients showed significantly lower levels of
      both PON1 and vitamin E in tissue and serum than the controls (p < 0.001).
      CONCLUSION: An association between oxidative stress and pathogenesis of these
      autoimmune diseases is identified. Attenuation of oxidative stress might be a
      relevant therapeutic approach and it would be useful to recommend additional
      drugs with antioxidant effects in the treatment of these conditions.

PMID- 22986953
TI  - Prevention and treatment of pertussis.

PMID- 22986949
TI  - Maraviroc intensification of stable antiviral therapy in HIV-1-infected patients
      with poor immune restoration: MARIMUNO-ANRS 145 study.
AB  - OBJECTIVE: To address the ability of a 24-week Maraviroc (MVC) intensification of
      a stable antiretroviral therapy (cART) to significantly increase the CD4 cell
      count slope. METHODS: Patients were eligible if they had CD4 <350 cells/mm, a CD4
      slope <50 cells/mm per year, and sustained plasma HIV-RNA <50 copies/mL over the
      last 2 years, while receiving a stable cART. Patients harboring pure X4-using
      viruses by a phenotypic tropism assay were excluded. MVC was added to cART for 24
      weeks, at the recommended dosage per drug-drug interactions. The primary endpoint
      was a significant positive difference in CD4 slopes (with MVC- pre-MVC, paired t
      test). RESULTS: Sixty patients (55 men), with median age 51 years, baseline CD4
      238 cells/mm, and slope before intensification +14.1 cells/mm per year were
      included. CD4 nadir was <50/mm in 47% of the population. The full set of patients
      (N = 57) completed week 24, and the on-treatment patients (N = 48) did not
      discontinue MVC. The median CD4 slope difference from baseline was +22.6 cells/mm
      per year (P = 0.08) in full set and +22.6 cells/mm per year (P = 0.04) in on
      treatment. Slope evolution was not different according to baseline tropism, CD4
      nadir, or ongoing cART regimen. No drug-related severe adverse events were
      recorded during intensification. MVC plasma concentrations were significantly
      different depending on drug-drug interaction with ongoing cART regimen and tended
      to be correlated with CD4 cells increase. CONCLUSION: In this study, MVC
      intensification of stable cART over 24 weeks was able to enhance CD4 cell slopes
      in patients with prior insufficient immune restoration despite long-term
      virological control.

PMID- 22986954
TI  - Endocarditis prophylaxis for dental procedures.

PMID- 22986955
TI  - Insect repellents.

PMID- 22986956
TI  - Bile duct injury during laparoscopic cholecystectomy without intraoperative
      cholangiography: a retrospective study on 1,100 selected patients.
AB  - BACKGROUND: Whether to routinely or selectively use intraoperative
      cholangiography (IOC) during laparoscopic cholecystectomy (LC) has been a
      controversial issue for many years. Many authors maintain that IOC decreases the
      rate of biliary complications such as bile duct injuries, biliary leak, and
      missed common bile duct (CBD) stones. However, in contrast to these claims, many
      centers have opted to perform LC without IOC. In this retrospective study, the
      results of a series of 1,100 LCs, all of which involved major biliary
      complications and which were performed without the use of IOC, were reviewed.
      METHODS: Data from 1,100 selected patients (728 females and 372 males) undergoing
      LC without the use of IOC from January 2003 to November 2011 were analyzed. One
      hundred and seventy LCs were performed by young surgeons during the learning
      curve, and 930 by surgeons with over 10 years of experience. Two techniques were
      used to create pneumoperitoneum: the Veress technique in 319 cases (29%) and the
      Hasson technique in the remaining 781 cases (71%). Patients with a suspicion of
      CBD stones were excluded from the study. RESULTS: Two CBD injuries (0.18%) and
      three biliary leaks (0.27%) were detected among this group. Thirty-three patients
      (3%) needed conversion to open cholecystectomy. Missed CBD stones were reported
      in 4 cases (0.36%). There was no postoperative mortality. CONCLUSION: LC can be
      performed safely without the use of IOC and with acceptable low rates of biliary
      complications. An accurate preoperative evaluation of clinical risk factors,
      precise operative procedures, and conversion to an open approach in doubtful
      cases are important measures which must be taken to prevent CBD injury.

PMID- 22986958
TI  - Could  this have happened to us?

PMID- 22986957
TI  - Effect of bolus volume and viscosity on pharyngeal automated impedance manometry
      variables derived for broad Dysphagia patients.
AB  - Automated impedance manometry (AIM) analysis measures swallow variables defining
      bolus timing, pressure, contractile vigour, and bolus presence, which are
      combined to derive a swallow risk index (SRI) correlating with aspiration. In a
      heterogeneous cohort of dysphagia patients, we assessed the impact of bolus
      volume and viscosity on AIM variables. We studied 40 patients (average age = 46
      years). Swallowing of boluses was recorded with manometry, impedance, and
      videofluoroscopy. AIMplot software was used to derive functional variables: peak
      pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir
      impedance to peak pressure (TNadImp-PeakP), the interval of impedance drop in the
      distal pharynx (flow interval, FI), upper oesophageal sphincter (UES) relaxation
      interval (UES RI), nadir UES pressure (Nad UESP), UES intrabolus pressure (UES
      IBP), and UES resistance. The SRI was derived using the formula SRI = (FI *
      PNadImp)/(PeakP * (TNadImp-PeakP + 1)) * 100. A total of 173 liquid, 44
      semisolid, and 33 solid boluses were analysed. The SRI was elevated in relation
      to aspiration. PeakP increased with volume. SRI was not significantly altered by
      bolus volume. PNadImp, UES IBP, and UES resistance increased with viscosity. SRI
      was lower with increased viscosity. In patients with dysphagia, the SRI is
      elevated in relation to aspiration, reduced by bolus viscosity, and not affected
      by bolus volume. These data provide evidence that pharyngeal AIM analysis may
      have clinical utility for assessing deglutitive aspiration risk to liquid
      boluses.

PMID- 22986959
TI  - [Replacement therapy at a standstill?].

PMID- 22986960
TI  - [A dying specialty?].

PMID- 22986961
TI  - [Tailored medicine or narcissomics?].

PMID- 22986967
TI  - [Measles and timing of vaccine].

PMID- 22986968
TI  - Pre-hospital treatment of stroke--time is brain.

PMID- 22986969
TI  - Prescriptions for ADHD  medication, 2004-08.
AB  - BACKGROUND: The use of medication for ADHD has increased significantly since the
      1990 s. The objective of this study was to establish the prescription rate for
      such drugs in Norway, and to examine which doctors prescribe them. MATERIAL AND
      METHOD: Data relating to all ADHD medication collected in the period 2004-08 was
      obtained from the Norwegian Prescription Database and linked to the GP database.
      RESULTS: The number of people who collected at least one prescription annually
      for ADHD medication increased over the period, while the number of new drug users
      remained stable. In 2008, 3.6 % of the boys and 1.2 % of the girls aged 11-15
      collected their prescriptions. Of the people who collected their prescriptions
      for the first time in 2005, 53 % continued to collect prescriptions every year
      throughout the period 2006-08. In 2008, extended-release methylphenidate
      constituted 51 % of the prescription volume for adults and 83 % for children and
      young people. GPs prescribed 17 % of the total volume collected in 2004 and 48 %
      in 2008. INTERPRETATION: During childhood and the teenage years there are
      substantial differences between the sexes when it comes to the prescription pick
      up rate for ADHD medication. This may suggest that girls who suffer from ADHD go
      through large parts of their statutory education before they are diagnosed and
      receive treatment. GPs play an important role in the treatment of ADHD.

PMID- 22986970
TI  - General practitioners' views  on drug-assisted rehabilitation.
AB  - BACKGROUND: The Norwegian model for opioid maintenance treatment (OMT) "Drug
      assisted rehabilitation" (DAR) is a cross-disciplinary tripartite model for the
      treatment of opioid dependence. The model requires collaboration among GPs, the
      social services and the specialist health services. To some degree it restricts
      the doctor's professional autonomy. The investigation aims to examine GPs'
      attitudes to the model and in particular the experiences of those who have
      actively participated. MATERIAL AND METHOD: An electronic questionnaire
      (Questback) was sent to Norwegian GPs listed on the members' register of the
      Norwegian Medical Association. The respondents were questioned about their
      general opinions of drug-assisted rehabilitation. Those who had had relevant
      patients were asked about their experiences and evaluations based on 22
      statements. RESULTS: 1,165 doctors (34 % of all registered GPs) responded to the
      survey. 155 (13 %) were negative, 395 (34 %) neutral, and 604 (53 %) were
      positive towards drug-assisted rehabilitation. 683 (59 %) were doctors with DAR
      experience. These were treating approximately 50 % of the country's DAR patients.
      The tripartite model received significant support. Very few want greater
      autonomy. The majority also support the strong emphasis on monitoring, although
      some, particularly older doctors with DAR experience, believe that urine tests
      could be replaced by personal contact. INTERPRETATION: Drug-assisted
      rehabilitation was mainly viewed positively by Norwegian GPs in this sample.
      There was little opposition to the doctor's role in the model, even though it
      restricts the autonomy of the individual doctor to some degree.

PMID- 22986971
TI  - [Risk of infection through use of selective  immunomodulating drugs for
      rheumatoid arthritis].
AB  - BACKGROUND: New drugs for rheumatoid arthritis (RA) have resulted in an
      improvement in patients' functioning and morbidity, but are linked with increased
      risk of infections. Traditional immunosuppressant drugs are often used in
      combination with anti-tumour necrosis factor-alpha (TNF-alpha) inhibitors or anti
      CD20 (rituximab). METHOD: The review is based on a search in PubMed and on the
      authors' own experience of treating infections in patients who receive
      immunosuppressant treatment. RESULTS: Traditional immunomodulating treatment
      results in an increased risk of infection. The disease RA in itself increases the
      risk of infections. There is evidence of an increased incidence of infections
      with both extracellular bacteria and intracellular microorganisms such as
      mycobacteria, including Mycobacterium tuberculosis, and viruses in patients who
      are treated with TNF-alpha inhibitors. Patients who are about to start taking TNF
      alpha inhibitors must therefore undergo a tuberculosis-risk assessment. Rituximab
      may increase the incidence of infection, but long-term observations are limited.
      Combination therapy involving different drugs that selectively modulate immune
      response is normally contraindicated because of the increased risk of infection.
      INTERPRETATION: The benefit of TNF-alpha inhibitors and rituximab treatment for
      RA must be weighed up against the increased risk of infections. Symptoms,
      findings and laboratory test results pertaining to serious infections may be
      influenced by immunomodulation therapy and thereby make clinical assessment
      difficult.

PMID- 22986972
TI  - [Tattoo and MRI].

PMID- 22986973
TI  - A young man with chest  pain.

PMID- 22986974
TI  - Chest pain can be many things.

PMID- 22986975
TI  - Former cancer patient in  her 40s with chest pain and increasing dyspnoea.

PMID- 22986976
TI  - Points in common, but different origins.

PMID- 22986977
TI  - [More patient participation].

PMID- 22986978
TI  - [Physicians relations to language errors].

PMID- 22986983
TI  - Pediatric injury outcomes in racial/ethnic minorities in California: diversity
      may reduce disparity.
AB  - HYPOTHESIS: Differences in health outcomes are well documented in adult
      racial/ethnic minorities. We hypothesize that similar differences exist in
      pediatric racial/ethnic minorities because their care is a function of their
      parents' access. We investigated this issue by examining pediatric injury
      outcomes in California. DESIGN: Retrospective analysis of the California Office
      of Statewide Health Planning and Development hospital discharge database.
      SETTING: Sample of all California hospitalized patients. PATIENTS: In a sample of
      patients aged 18 years or younger at admission, injury patients were defined as
      having International Classification of Diseases, Ninth Revision, primary
      diagnosis codes between 800 and 959, with certain exclusions, from January 1,
      1999, through December 31, 2010. MAIN OUTCOME MEASURES: Adjusted risk of in
      hospital death, controlling for age, sex, injury severity measured by survival
      risk ratio, Charlson comorbidity index, insurance status, admission year,
      teaching hospital status, and mechanism of injury. RESULTS: A total of 47 000
      pediatric patients were identified. Bivariate analysis showed a significant
      difference in mortality by race/ethnicity among non-Hispanic whites (0.8%),
      blacks (1.2%), Hispanics (1.1%), Asians (1.2%), and American Indians/others
      (0.6%) (P = .01). However, with the exception of Asians (odds ratio, 0.32; 95%
      CI, 0.11-0.90), adjusted odds ratios of death relative to non-Hispanic whites for
      blacks (1.33; 0.71-2.46), Hispanics (1.06; 0.71-1.58), and American
      Indians/others (0.60; 0.17-2.10) showed no significant differences. CONCLUSIONS:
      Unlike previous studies that have shown that adult racial/ethnic minorities (age,
      18-64 years) have higher mortality relative to non-Hispanic whites, our study
      demonstrated no significant racial/ethnic differences among pediatric patients
      with injuries. It may be that differential access does not exist for children. In
      addition, it may also be possible that the diversity in California leads to
      culturally competent care and such care has been reported to improve patient
      outcomes.

PMID- 22986984
TI  - Myo-inositol treatment and GABA-A receptor subunit changes after kainate-induced
      status epilepticus.
AB  - Identification of compounds preventing the biochemical changes that underlie the
      epileptogenesis process is of great importance. We have previously shown that myo
      Inositol (MI) daily treatment prevents certain biochemical changes that are
      triggered by kainic acid (KA)-induced status epilepticus (SE). The aim of the
      current work was to study the further influence of MI treatment on the
      biochemical changes of epileptogenesis and focus on changes in the hippocampus
      and neocortex of rats for the following GABA-A receptor subunits: alpha1, alpha4,
      gamma2, and delta. After SE, one group of rats was treated with saline, while the
      second group was treated with MI. Control groups that were not treated by the
      convulsant received either saline or MI administration. 28-30 h after the
      experiment, a decrease in the amount of the alpha1 subunit was revealed in the
      hippocampus and MI had no significant influence on it. On the 28th day of the
      experiment, the amount of alpha1 was increased in both the KA- and KA + MI
      treated groups. The alpha4 and gamma2 subunits were strongly reduced in the
      hippocampus of KA-treated animals, but MI significantly halted this reduction.
      The effects of MI on alpha4 and gamma2 subunit changes were significantly
      different between hippocampus and neocortex. On the twenty-eighth day after SE, a
      decrease in the amount of alpha1 was found in the neocortex, but MI treatment had
      no effect on it. The obtained results indicate that MI treatment interferes with
      some of the biochemical processes of epileptogenesis.

PMID- 22986985
TI  - Perceiving the chemical language of Gram-negative bacteria: listening by high
      resolution mass spectrometry.
AB  - Gram-negative bacteria use N-acylhomoserine lactones (AHLs) as their command
      language to coordinate population behavior during invasion and colonization of
      higher organisms. Although many different bacterial bioreporters are available
      for AHLs monitoring, in which a phenotypic response, e.g. bioluminescence,
      violacin production, and beta-galactosidase activity, is exploited, mass
      spectrometry (MS) is the most versatile detector for rapid analysis of AHLs in
      complex microbial samples, with or without prior separation steps. In this paper
      we critically review recent advances in the application of high-resolution MS to
      analysis of the quorum sensing (QS) signaling molecules used by Gram-negative
      bacteria, with much emphasis on AHLs. A critical review of the use of
      bioreporters in the study of AHLs is followed by a short methodological survey of
      the capabilities of high-resolution mass spectrometry (HRMS), including Fourier
      transform ion cyclotron resonance (FTICR) MS and quadrupole time-of-flight (qTOF)
      MS. Use of infusion electrospray ultrahigh-resolution FTICR MS (12 Tesla) enables
      accurate mass measurements for determination of the elemental formulas of AHLs in
      Acidovorax sp. N35 and Burkholderia ubonensis AB030584. Results obtained by
      coupling liquid chromatography with a hybrid quadrupole linear ion trap-FTICR
      mass spectrometer (LC-LTQ-FTICRMS, 7-T) for characterization of acylated
      homoserine lactones in the human pathogen Pseudomonas aeruginosa are presented.
      UPLC-ESI-qTOF MS has also proved to be suitable for identification of 3O-C(10)HSL
      in Pseudomonas putida IsoF cell culture supernatant. Aspects of sample
      preparation and the avoidance of analytical pitfalls are also emphasized.

PMID- 22986986
TI  - Bead affinity chromatography in a temperature-controllable microsystem for
      biomarker detection.
AB  - This paper describes a temperature-controllable bead affinity chromatography
      (BAC) in a microsystem for biomarker detection, and preparing samples for matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS) analysis. Cancer marker proteins were captured in the microsystem by BAC with
      RNA aptamer-immobilized microbeads. The captured proteins were then denatured and
      released from the microbeads by controlling temperature. The microsystem consists
      of a microreactor for trapping microbeads and a temperature control unit for
      thermal treatment of the trapped beads. We used polymethylsilxoane or single
      crystalline silicon in fabricating two different types of reaction chamber to
      compare the differences in performance originated from the materials.
      Carcinoembryonic antigen was concentrated and purified from human serum using the
      microsystem and detected by MALDI-TOF MS to demonstrate the usefulness of the
      microsystem. The microsystem simplifies a sample preparation process required for
      protein analysis and cancer biomarker detection, which will accelerate the
      process of cancer research.

PMID- 22986987
TI  - Isolation and characterization of degradation products of moxidectin using LC,
      LTQ FT-MS, H/D exchange and NMR.
AB  - This study aimed to evaluate the degradation profile and pathways, and identify
      unknown impurities of moxidectin under stress conditions. During the experiments,
      moxidectin samples were stressed using acid, alkali, heat and oxidation, and
      chromatographic profiles were compared with known impurities given in European
      Pharmacopeia (EP) monograph. Moxidectin has shown good stability under heat,
      while reaction with alkali produced 2-epi and ?2,3 isomers (impurities D and E in
      EP) by characteristic reactions of the oxahydrindene (hexahydrobenzofuran)
      portion of the macrocyclic lactone. Two new, previously unreported, unknown
      degradation products, i.e. impurity 1 and impurity 2, detected after acid
      hydrolysis of moxidectin (impurity 2 was also observed to a lesser extent after
      oxidation), were isolated from sample matrices and identified using liquid
      chromatography, NMR, high-resolution FT-ICR MS, and hydrogen/deuterium exchange
      studies. FTMS analysis showed accurate mass of molecular ion peaks for moxidectin
      at m/z 640.38412, impurity 1 at m/z 656.37952 and impurity 2 at m/z 611.35684,
      giving rise to daughter ions traceable up to the seventh levels of MS(n)
      experiments and supporting the proposed structures. Both unknown impurities along
      with moxidectin were fully characterized by (1)H, (13)C, 1D HMBC and 2D (NOESY,
      COSY and HSQC) NMR experiments. The interpretation of experimental data
      positively identified impurity 1 as 3,4-epoxy-moxidectin and impurity 2 as 23
      keto-nemadectin. The identification of new impurities and correlation of their
      chromatographic profiles with the EP method is very useful to establish the
      stability profile of moxidectin and its preparations, as well as add value to the
      forthcoming moxidectin finished product European Pharmacopeia monographs.

PMID- 22986988
TI  - Is it possible to agree on a value for inorganic arsenic in food? The outcome of
      IMEP-112.
AB  - Two of the core tasks of the European Union Reference Laboratory for Heavy Metals
      in Feed and Food (EU-RL-HM) are to provide advice to the Directorate General for
      Health and Consumers (DG SANCO) on scientific matters and to organise proficiency
      tests among appointed National Reference Laboratories. This article presents the
      results of the 12th proficiency test organised by the EU-RL-HM (IMEP-112) that
      focused on the determination of total and inorganic arsenic in wheat, vegetable
      food and algae. The test items used in this exercise were: wheat sampled in a
      field with a high concentration of arsenic in the soil, spinach (SRM 1570a from
      NIST) and an algae candidate reference material. Participation in this exercise
      was open to laboratories from all around the world to be able to judge the state
      of the art of the determination of total and, more in particular, inorganic
      arsenic in several food commodities. Seventy-four laboratories from 31 countries
      registered to the exercise; 30 of them were European National Reference
      Laboratories. The assigned values for IMEP-112 were provided by a group of seven
      laboratories expert in the field of arsenic speciation analysis in food.
      Laboratory results were rated with z and zeta scores (zeta scores) in accordance
      with ISO 13528. Around 85 % of the participants performed satisfactorily for
      inorganic arsenic in vegetable food and 60 % did for inorganic arsenic in wheat,
      but only 20 % of the laboratories taking part in the exercise were able to report
      satisfactory results in the algae test material.

PMID- 22986989
TI  - Determination of nitrite, nitrate, bromide, and iodide in seawater by ion
      chromatography with UV detection using dilauryldimethylammonium-coated monolithic
      ODS columns and sodium chloride as an eluent.
AB  - A method was developed for determination of inorganic anions, including nitrite
      (NO(2)(-)), nitrate (NO(3)(-)), bromide (Br(-)), and iodide (I(-)), in seawater
      by ion chromatography (IC). The IC system used two dilauryldimethylammonium
      bromide (DDAB)-coated monolithic ODS columns (50 * 4.6 mm i.d. and 100 * 4.6 mm
      i.d.) connected in series for separation of the ions. Aqueous NaCl (0.5 mol/L;
      flow rate, 3 mL/min) containing 5 mmol/L phosphate buffer (pH 5) was used as the
      eluent, and detection was with a UV detector at 225 nm. The monolithic ODS
      columns were coated and equilibrated with a 1-mmol/L DDAB solution (in
      H(2)O/methanol, 90:10 v/v). The hydrophilic ions (NO(2)(-), NO(3)(-), and Br(-))
      were separated within 3 min and the retention time of I(-) was 16 min. No
      interferences from matrix ions, such as chloride and sulfate ions, were observed
      in 35 0/00 artificial seawater. The detection limits were 0.6 MUg/L for NO(2)(-),
      1.1 MUg/L for NO(3)(-), 70 MUg/L for Br(-), and 1.6 MUg/L for I(-) with a 200-MUL
      sample injection. The performance of the coated columns was maintained without
      addition of DDAB in the eluent. The IC system was successfully applied to real
      seawater samples with recovery rates of 94-108 % for all ions.

PMID- 22986990
TI  - Convenient synthesis of fluoride-alkoxides of Nb(V) and Ta(V): a spectroscopic,
      crystallographic and computational study.
AB  - The synthesis and the spectroscopic characterization of fluoride-alkoxides of
      niobium and tantalum in the highest oxidation state are reported. Suspensions of
      MF(5) (M = Nb, Ta) in a chlorinated solvent reacted with up to three equivalents
      of ROSiMe(3) (R = Me, Et, Ph) to afford polynuclear derivatives and variable
      amounts of FSiMe(3). Thus MF(4)(OR) (R = Et, Ph) and MF(3)(OR)(2) were obtained
      by selective 1 : 1 and 1 : 2 reactions almost exclusively as single isomeric
      products; otherwise mixtures of MF(4)(OMe) species were afforded from the
      equimolar reactions of MF(5) with MeOSiMe(3). The 1 : 3 reaction of TaF(5) with
      MeOSiMe(3) led to different forms of TaF(2)(OMe)(3). The synthesis of TaF(OPh)(4)
      was forced by high temperature conditions or the use of a large excess of
      PhOSiMe(3). DFT studies were carried out in order to predict, in the distinct
      cases, the most stable structures of the metal products. The molecular structures
      of [NbF(2)(OPh)(2)(MU-F)](3) and [TaF(OPh)(3)(MU-OPh)](2) were ascertained by X
      ray diffraction.

PMID- 22986991
TI  - Hospital readmission among elderly patients.
AB  - This study investigates the incidence and determinants of hospital readmissions
      among elderly patients in Norway. The analyses are based on registered data on
      inpatient admissions to public hospitals from 1999 to 2006. During this period,
      mean length of stay in hospital decreased, while readmission rates increased.
      Probit and instrumental variable regression models are applied for the analyses.
      The results indicate that longer length of stay in the hospital is associated
      with lower probability of readmission. A patient's age, comorbidities, and
      complexity of the treatment procedure are positively associated with
      readmissions, while higher number of diagnostic procedures negatively affects
      hospital readmission. Finally, patients discharged to institutions are more
      likely to be readmitted to the hospital. 

PMID- 22986992
TI  - Patients' access to biologics in rheumatoid arthritis: a comparison between
      Portugal and other European countries.
AB  - BACKGROUND: Despite the widespread availability of biologics across Europe,
      rheumatoid arthritis (RA) patients' access to these drugs differs significantly
      among countries. OBJECTIVES: To compare the proportion of RA patients treated
      with biologics across Europe and investigate the factors that most influence it,
      with focus on the Portuguese case, reportedly with low access rates to biologics.
      METHODS: The biologics' market was characterized for 15 selected European
      countries. Variables potentially influencing patients' access to biologics (PAB)
      in RA were also collected, including demographic, disease, economic, funding and
      biologics' market-related data. A multivariable regression model identified the
      factors that best explain PAB. Based on these determinants, a cluster analysis
      was performed to group the countries with most similar behaviour regarding PAB
      allowing the evaluation of Portugal's relative position among these countries.
      RESULTS: The regression model (R(2) = 0.953) indicated that PAB in selected
      countries is explained mostly by its gross domestic product (GDP) per capita, the
      usage of methotrexate (MTX) and the biologics' distribution channel. Current MTX
      usage in Portugal shows similarity with practice from UK, France, Germany or
      Spain 5 years before, explaining why PAB in Portugal stood at 7% in 2010, 12
      percentage points below the average of selected countries. CONCLUSIONS:
      Variations in RA PAB were found across selected countries with Portugal showing
      the lowest proportion. GDP per capita, biologics distribution channel and
      consumption of MTX appear to be the best explanatory factors for these
      fluctuations in European countries.

PMID- 22986993
TI  - Twist confers chemoresistance to anthracyclines in bladder cancer through
      upregulating P-glycoprotein.
AB  - BACKGROUND: The membrane transporter P-glycoprotein (P-gp) was found to mediate
      chemoresistance, which is one of the obstacles to effective chemotherapy in
      several types of human cancer. The transcription factor Twist, which has been
      reported to participate in cancer invasion and metastasis, also plays a vital
      role in the progression of chemoresistance. However, the effect of Twist on P-gp
      related chemoresistance remains dubious. METHODS AND RESULTS: We found that Twist
      can regulate the expression of P-gp and then confer resistance to anthracycline
      drugs in human bladder cancer cells. Firstly, Twist was found to be coexpressed
      with P-gp in human bladder cancer cells and tissues, which were associated with
      enhanced chemoresistance to anthracycline drugs. Secondly, knockdown of Twist by
      specific siRNA treatment significantly sensitized bladder cancer cells to
      anthracycline drugs via inhibiting P-gp expression. Bladder cancer cells that
      survived transient exposure to anthracycline drugs showed higher levels of P-gp
      expression and more nuclear localization of Twist than untreated cells.
      CONCLUSION: We report a novel mechanism of anthracycline chemoresistance in
      bladder cancer in which activated Twist mediates P-gp expression in addition to
      its antiapoptotic roles. Therapeutic strategies targeting Twist may improve the
      management of recurrent bladder cancer after chemotherapy.

PMID- 22986995
TI  - Mania: diagnosis and treatment recommendations.
AB  - This article provides recommendations for the diagnosis and treatment of mania,
      which characterizes bipolar I disorder (BD I). Failure to detect mania leads to
      misdiagnosis and suboptimal treatment. To diagnose mania, clinicians should
      include a detailed mood history within their assessment of patients presenting
      with depression, agitation, psychosis or insomnia. With regards to treatment, by
      synthesizing the findings from recent treatment guidelines, and reviewing
      relevant literature, this paper has distilled recommendations for both acute and
      long-term management. Antimanic agents including atypical antipsychotics and
      traditional mood stabilizers are employed to reduce acute manic symptoms,
      augmented by benzodiazepines if needed, and in refractory or severe cases with
      behavioural and/or psychotic disturbance, electroconvulsive therapy may
      occasionally be necessary. Maintenance/prophylaxis therapy aims to reduce
      recurrences/relapse, for which the combination of psychological interventions
      with pharmacotherapy is beneficial as it ensures adherence and monitoring of
      tolerability.

PMID- 22986994
TI  - Distributions of active spinal cord neurons during swimming and scratching motor
      patterns.
AB  - The spinal cord can generate motor patterns underlying several kinds of limb
      movements. Many spinal interneurons are multifunctional, contributing to multiple
      limb movements, but others are specialized. It is unclear whether anatomical
      distributions of activated neurons differ for different limb movements. We
      examined distributions of activated neurons for locomotion and scratching using
      an activity-dependent dye. Adult turtles were stimulated to generate repeatedly
      forward swimming, rostral scratching, pocket scratching, or caudal scratching
      motor patterns, while sulforhodamine 101 was applied to the spinal cord.
      Sulforhodamine-labeled neurons were widely distributed rostrocaudally,
      dorsoventrally, and mediolaterally after each motor pattern, concentrated
      bilaterally in the deep dorsal horn, the lateral intermediate zone, and the
      dorsal to middle ventral horn. Labeled neurons were common in all hindlimb
      enlargement segments and the pre-enlargement segment following swimming and
      scratching, but a significantly higher percentage were in the rostral segments
      following swimming than rostral scratching. These findings suggest that largely
      the same spinal regions are activated during swimming and scratching, but there
      are some differences that may indicate locations of behaviorally specialized
      neurons. Finally, the substantial inter-animal variability following a single
      kind of motor pattern may indicate that essentially the same motor output is
      generated by anatomically variable networks.

PMID- 22986996
TI  - New models for considering the role of medication in the treatment and
      elucidation of the etiology of autism.
AB  - Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Over
      the past decades, much research has been conducted to elucidate a single
      etiological factor and effective pharmacotherapuetics to address the core symptom
      domains of ASD with limited success. Research has changed focus from behavioral
      observations of ASD to translating findings from animal models, genomic
      manipulation studies and basic science studies to pharmacological agents with the
      aim to lessen or reverse core symptoms of ASD. This paper evaluates potential
      models for translating information from the biology of ASD to pharmacological
      treatments.

PMID- 22986997
TI  - Synthesis, antibacterial activity and mode of action of novel linoleic acid
      dipeptide-spermidine conjugates.
AB  - Towards therapeutically viable mimics of host defense cationic peptides (HDCPs)
      here we report the design and synthesis of a small library, based on a novel
      hydrophobic-dipeptide-spermidine template. Lipidated sequences 11, 14, 15, 16, 18
      and 19 exhibited potent activity against susceptible as well as drug resistant
      Gram-positive and Gram-negative bacterial strains. Structure-activity
      relationships of the template revealed a hydrophobicity window of 50-70% with
      minimum +2 charges to be crucial for activity and cell selectivity. Active
      sequences 14, 15 and 16 exhibited different modes of action based on dipeptide
      composition as revealed by studies on model membranes, intact bacterial cells and
      DNA. Further, severe damage to surface morphology of methicillin resistant S.
      aureus caused by 14, 15 and 16 at 10 * MIC was observed. The present study
      provides us two active sequences (14 and 16) with a membrane perturbing mode of
      action, cell selectivity to hRBCs and keratinocytes along with potent activity
      against clinically relevant pathogen MRSA. The designed template thus may prove
      to be a suitable probe to optimize sequences for better selectivity and potential
      to combat a wide range of drug resistant strains in further research.

PMID- 22986998
TI  - Ivano Bertini: 1940-2012.
AB  - Ivano Bertini left us on 7 July after a short illness. The chemical, biological
      and biomedical communities--indeed, society at large--have lost a unique and
      magnetic personality that will not be easily forgotten by those who have known
      him personally.

PMID- 22987007
TI  - Orchestrating hi-fi annotations.
AB  - By incorporating sequence homology and context associations, global probabilistic
      approaches to annotate genome-scale metabolic networks can substantially improve
      the accuracy of biochemical predictions, revealing potential functionality and
      directing experimental validation.

PMID- 22987008
TI  - Tafazzin senses curvature.
AB  - The phospholipid-lysophospholipid transacylase tafazzin is responsible for
      enrichment of the cardiolipin fraction of mitochondria with tetralinoleoyl
      cardiolipin. The specificity for linoleoyl hydrocarbon chains is now explained by
      the specific action of tafazzin on negatively curved lipid monolayers.

PMID- 22987009
TI  - GhoSTly bacterial persisters.
AB  - Bacterial persisters consist of a phenotypic subpopulation that survives
      antibiotic treatment, prolonging infection. The GhoT toxin from the newly
      discovered ghoS-ghoT toxin-antitoxin system contributes to persistence, most
      likely by interfering with bacterial inner membrane integrity.

PMID- 22987010
TI  - New first-trimester crown-rump length equations from a French general population.
AB  - INTRODUCTION: The purpose of this study was to obtain precise knowledge of fetal
      biometric measurements, in particular crown-rump length (CRL). Our results have
      been carefully compared to equations found in the literature. MATERIALS AND
      METHODS: Single-operator measurements of 2,123 spontaneous pregnancies from a
      general French population provided new statistical relationships between fetal
      age (FA) and CRL. Comparisons were made with measurements obtained from 402 in
      vitro fertilizations (IVFs) for which FA were known. Heteroskedastic and robust
      regressions were compared by cross-validation, and prediction errors were
      studied. All ultrasound measurements were taken during standard follow-ups of
      pregnancies, without any additional features. RESULTS: From a cleaned subsample
      of 513 spontaneous pregnancies, we reported good modeling of first-term embryonic
      growth, with equations and predictions of standard deviations agreeing with
      objective datations for IVFs. Most precise CRL measurements were predicted for FA
      of 49 days. DISCUSSION: Our results allow future detection of fetal growth
      abnormalities using Z-scores throughout the first trimester.

PMID- 22987011
TI  - An unmeasured harm of screening.

PMID- 22987012
TI  - Evaluation of a parent led curriculum in developmental disabilities for pediatric
      and medicine/pediatric residents.
AB  - Families of children with special health care needs (CSHCN) want to partner with
      their physicians to provide family-centered care and a medical home for their
      children. A parent group independently developed a parent-led curriculum to
      assist in the training of residents for this purpose. The objective of this study
      was to evaluate pediatric residents' satisfaction with and perceived relevance of
      this parent-led curriculum demonstrating the effects a disability has on the
      child and family. From 2002 to 2009, 188 residents participated in a parent
      interview and a home visit with families of CSHCN through Project DOCC(SM)
      (Delivery of Chronic Care), as part of their required developmental disabilities
      rotation. Residents voluntarily completed anonymous quantitative surveys
      regarding the parent interview and home visit, rating the Parent Presenters,
      Information Provided, Depth of Coverage, Relevance to Future Practice, and
      Overall Satisfaction. Scores were reported on a Likert scale: 1 = Poor, 2 = Fair,
      3 = Satisfactory, 4 = Very Good, and 5 = Excellent. Qualitative comments
      regarding the residents' experience on the quality and relevance of the
      curriculum were also received. 112 (60 %) residents completed the survey for the
      parent interview and 96 (51 %) for the home visit. Average scores and standard
      deviations were calculated for each variable. Results for the parent interview:
      Presenters = 4.76 +/- 0.52, Information = 4.40 +/- 0.73, Depth = 4.59 +/- 0.67,
      Relevance = 4.47 +/- 0.73, and Satisfaction = 4.64 +/- 0.60. Results for the home
      visit: Presenters = 4.68 +/- 0.62, Information = 4.25 +/- 0.89, Depth = 4.46 +/-
      0.82, Relevance = 4.40 +/- 0.75, and Satisfaction = 4.49 +/- 0.74. The overall
      experience was favorable with qualitative comments such as: excellent, eye
      opening, humbling, informative, valuable, and relevant. Pediatric residents rated
      this parent-led curriculum "very good" to "excellent" overall. Residents were
      highly satisfied with all areas assessed and felt that it was relevant to their
      future practices. Parent-led curricula regarding care of children with
      disabilities can be incorporated into and enhance pediatric resident training
      programs. 

PMID- 22987013
TI  - External stenting of pancreaticojejunostomy anastomosis and pancreatic duct after
      pancreaticoduodenectomy.
AB  - Pancreatic fistula is a major cause of morbidity and mortality after
      pancreaticoduodenectomy. External drainage of pancreaticojejunostomy anastomosis
      with a stent is used to reduce the rate of pancreatic fistula. This study
      compares the rates of pancreatic fistula between external stent drainage versus
      no-stent drainage for pancreaticojejunal anastomosis following
      pancreaticoduodenectomy. A total of 53 patients undergoing
      pancreaticoduodenectomy for various benign and malignant pathologies were
      included in the study. An external stent was inserted across the anastomosis to
      drain the pancreatic duct in 26 patients and 27 patients received no stent. The
      primary end point was pancreatic fistula. All surgeries were done by a single
      surgeon with expertise in hepatobiliary pancreatic surgery at a single institute.
      The two groups were comparable in demographic data, underlying pathologies,
      presenting complaints, presence of comorbid illnesses and proportion of patients
      with preoperative biliary drainage, pancreatic consistency and duct diameter. The
      pancreatic fistula rates were similar in both the groups (11.5 vs. 14.8 %, P =
      0.725). The morbidity and surgical re-exploration rate were statistically not
      significant between the two groups (65.4 vs. 51.9 %, P = 0.318 and 11.5 vs. 7.4
      %, P = 0.60). Postoperative stay was also similar with a mean of 14 days in both
      the groups (P = 0.66). The mortality rate was statistically not significant in
      the two groups (3.8 vs. 7.4 %, P = 0.575). External drainage of
      pancreaticojejunostomy anastomosis and the pancreatic duct with a stent does not
      decrease the rate of postoperative pancreatic fistula after
      pancreaticoduodenectomy.

PMID- 22987014
TI  - General surgeons' views on Oncologic Multidisciplinary Group meetings as part of
      colorectal cancer care.
AB  - This study aimed to assess the current effectiveness of Oncologic
      Multidisciplinary Groups (OMGs) meetings across central Tuscany through surgeons'
      reports and their individual perceived benefits on colorectal cancer management.
      One hundred and sixty-seven general surgeons received a questionnaire with 21
      questions covering organizational characteristics of OMGs and the individual
      perceived benefits of OMGs. The responses were analyzed by hospital setting
      (teaching vs. community hospital). The reply rate was 62.8 %, and 82 respondent
      surgeons (49.1 %) were involved in the treatment of colorectal cancer patients.
      At community hospitals, there was a more frequent participation of medical
      oncologists, radiation oncologists and pathologists; a less selection of
      discussed cases was performed; and almost all decisions were inserted into
      official patient charts (p < 0.05). Community hospital surgeons perceived more of
      a benefit than academic surgeons: OMGs ensure that all treatment options are
      considered and improve timeliness of care, patient outcomes, patient satisfaction
      and communication with patients (p < 0.05). The surveyed surgeons reported that
      OMGs offer a modest degree of protection from malpractice but improve
      communications between colleagues and are an opportunity for personal
      professional development. Professionals regularly participating in well-conducted
      and well-organized OMGs for colorectal cancer felt that the multidisciplinary
      strategy may be advantageous to both patients and caregivers.

PMID- 22987016
TI  - The complex factors determining neonatal abstinence syndrome and its management.

PMID- 22987015
TI  - Measurement of factor v activity in human plasma using a microplate coagulation
      assay.
AB  - In response to injury, blood coagulation is activated and results in generation
      of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which
      forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated
      form, FVa, is a critical cofactor for the protease FXa and accelerator of
      thrombin generation during fibrin clot formation as part of prothrombinase (1,
      2). Manual FV assays have been described (3, 4), but they are time consuming and
      subjective. Automated FV assays have been reported (5-7), but the analyzer and
      reagents are expensive and generally provide only the clot time, not the rate and
      extent of fibrin formation. The microplate platform is preferred for measuring
      enzyme-catalyzed events because of convenience, time, cost, small volume,
      continuous monitoring, and high-throughput (8, 9). Microplate assays have been
      reported for clot lysis (10), platelet aggregation (11), and coagulation Factors
      (12), but not for FV activity in human plasma. The goal of the method was to
      develop a microplate assay that measures FV activity during fibrin formation in
      human plasma. This novel microplate method outlines a simple, inexpensive, and
      rapid assay of FV activity in human plasma. The assay utilizes a kinetic
      microplate reader to monitor the absorbance change at 405 nm during fibrin
      formation in human plasma (Figure 1) (13). The assay accurately measures the
      time, initial rate, and extent of fibrin clot formation. It requires only MUl
      quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to
      24-80 pM FV, and measures the amount of unintentionally activated (1-stage
      activity) and thrombin-activated FV (2-stage activity) to obtain a complete
      assessment of its total functional activity (2-stage activity - 1-stage
      activity). Disseminated intravascular coagulation (DIC) is an acquired
      coagulopathy that most often develops from pre-existing infections (14). DIC is
      associated with a poor prognosis and increases mortality above the pre-existing
      pathology (15). The assay was used to show that in 9 patients with DIC, the FV 1
      stage, 2-stage, and total activities were decreased, on average, by 54%, 44%, and
      42%, respectively, compared with normal pooled human reference plasma (NHP). The
      FV microplate assay is easily adaptable to measure the activity of any
      coagulation factor. This assay will increase our understanding of FV biochemistry
      through a more accurate and complete measurement of its activity in research and
      clinical settings. This information will positively impact healthcare
      environments through earlier diagnosis and development of more effective
      treatments for coagulation disorders, such as DIC.

PMID- 22987017
TI  - Grape seed proanthocyanidin extracts enhance endothelial nitric oxide synthase
      expression through 5'-AMP activated protein kinase/Surtuin 1-Krupple like factor
      2 pathway and modulate blood pressure in ouabain induced hypertensive rats.
AB  - Grape seed proanthocyanidin extracts (GSPE) belonging to polyphenols, possess
      various biological effects including anti-inflammation, anti-oxidant, anti-aging,
      anti-atherosclerosis, etc. GSPE is potential in regulating endothelial function.
      However, the underlying mechanism is not clear yet. In this study, by small
      interfering RNA (siRNA) knocking down, we proved that GSPE increase endothelial
      nitric oxide synthase (eNOS) expression in human umbilical vessel cells (HUVECs)
      in vitro, which was attributed to its transcription factor Krupple like factor 2
      (KLF2) induction. Furthermore, GSPE activate 5'-AMP activated protein kinase
      (AMPK) and increase surtuin 1 (SIRT1) protein level, critical for KLF2 induction.
      We also illuminated the role of GSPE in hypertension treatment. By chronic
      administration of GSPE in ouabain induced hypertensive rats model, we access the
      effect of GSPE on blood pressure regulation and the possible mechanisms involved.
      After 5 weeks feeding, GSPE significantly block the ouabain induced blood
      pressure increase. The aortic NO production impaired by ouabain was improved. In
      conclusion, GSPE increase eNOS expression and NO production in an AMPK/SIRT1
      dependent manner through KLF2 induction, and attenuate ouabain induced
      hypertension.

PMID- 22987018
TI  - Intrinsic cerebral connectivity analysis in an untreated female-to-male
      transsexual subject: a first attempt using resting-state fMRI.
AB  - BACKGROUND/AIMS: Transsexualism is a gender identity disorder whose
      symptomatology could involve cognitive, neurobiological and psychological
      variance from biological sex standard. Several evidences support the hypothesis
      of a structural and functional brain reorganization in transgender subjects, with
      a different impact for male-to-female and female-to-male (FtM) subjects. Here we
      used resting-state fMRI to understand the similarities between the spontaneous
      brain connectivity of an untreated FtM subject and two male and female control
      groups. METHODS: Both seed-voxel and atlas-based region-of-interest (ROI)
      approaches were used. RESULTS: Brain areas sensitive to gender dimorphism like
      left lingual gyrus and precuneus showed strong similarities between the FtM
      subject and female control group with respect to control males, with comparable
      extension and location of functional connectivity maps. ROI analysis confirmed
      this evidence, highlighting a greater pattern of differences between the FtM
      subject and males and the FtM subject and females. No difference between seed
      voxel results in the FtM subject and females was found. CONCLUSION: These data
      partially support the idea that untreated FtM transgender shows a functional
      connectivity profile comparable to female control subjects.

PMID- 22987021
TI  - Perceived discrimination is a potential contributing factor to substance use and
      mental health problems among primary care patients in Chile.
AB  - OBJECTIVES: Perceived discrimination is a prevalent problem that has been linked
      to negative health outcomes for victims. The goal of this research was to examine
      whether perceived discrimination within the past 6 months was related to 6-month
      prevalence of problem drinking, illicit drug use, major depressive disorder
      (MDD), and posttraumatic stress disorder (PTSD) in a sample of primary care
      patients in Chile. METHODS: Structured diagnostic assessments were administered
      to assess for MDD and PTSD using the Composite International Diagnostic
      Interview. The Alcohol Use Disorders Identification Test assessed hazardous
      alcohol use. Additional measures captured illegal drug use and discrimination in
      the past 6 months. Measures were administered to 2839 participants between the
      ages of 15 to 98 in primary care centers in the Chilean cities of Concepcion and
      Talcahuano. RESULTS: Controlling for demographic variables and previous trauma
      victimization, patients who reported discrimination in the past 6 months were
      significantly more likely to engage in hazardous alcohol use, illegal drug use,
      be diagnosed with MDD, and PTSD within this same time period than patients not
      reporting discrimination. CONCLUSIONS: This study highlights the importance of
      considering discrimination as a potential contributing factor to substance use
      and mental health problems in a Latin American sample.

PMID- 22987020
TI  - A pilot study for the early assessment of the effects of BMS-754807 plus
      gefitinib in an H292 tumor model by [(18)F]fluorothymidine-positron emission
      tomography.
AB  - BMS-754807 is an inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and
      insulin receptor that also represses aurora kinase. Cancers that express high
      levels of IGF-1/IGF-1R are sensitive to BMS-754807; however, it shows limited
      efficacy in non-small cell lung cancer (NSCLC) in which IGF-1R-driven signals may
      not be dominant factors in cell proliferation. In this study, we investigated
      whether a combination of BMS-754807 and gefitinib would be synergistic in H292
      NSCLC and whether [(18)F]fluorothymidine ([(18)F]FLT)-positron emission
      tomography (PET) could predict the effects. We found that BMS-754807 synergized
      with gefitinib in reducing cell viability (combination index=0.38) and Akt
      phosphorylation, and increasing the subG1 fraction in H292 cells. BMS-754807
      alone and in combination with gefitinib increased the cells in G2M phase and
      polyploid cells and decreased the phosphorylation of IGF-1R and histone H3. The
      inhibition of tumor growth by gefitinib was increased by BMS-754807 (%T/C, 17.5 %
      vs. 58.0 % for gefitinib alone and combined treatment, respectively), although
      BMS-754807 alone had little effect. The standardized uptake value by [(18)F]FLT
      PET were increased in vehicle-treated mice by 73 %, minimally changed in
      gefitinib- or BMS-754807-treated mice, whereas decreased in co-treated mice by 
      48.8 % between day 0 and day 3. The combination therapy with BMS-754807 and
      gefitinib might be a more effective anticancer strategy than BMS-754807 alone in
      tumors that are less IGF-1R-dependent and that [(18)F]FLT-PET can be used to
      assess early therapeutic responses.

PMID- 22987023
TI  - No short-term cytogenetic consequences of Hungarian red mud catastrophe.
AB  - Red mud is an industrial waste produced in the process of alumina extraction from
      bauxite with concentrated NaOH. When the red mud-containing reservoir collapsed
      in Ajka Alumina Plant Hungary in October 2010, the most serious immediate effects
      were caused by the high alkalinity (pH >= 13) of the flood. Many persons suffered
      burn-like damage to tissues and contact with caustic desiccated ultra-fine dust
      with traces of toxic metals also caused irritation of upper respiratory tract and
      eyes. This catastrophe was unique from the point of view of genotoxic effects as
      well. Therefore cytogenetic examinations were carried out on inhabitants, either
      with burns (17 persons) or on those inhaling desiccated caustic dust (42
      persons). Chromosomal aberration (CA) analysis and bleomycin (BLM)-sensitivity
      assays, as possible markers of effects, were studied in peripheral blood
      lymphocytes of persons within 4-6 weeks following the catastrophe. Controls were
      matched for age, sex and smoking habits, and also places of residence with
      different constituents of air pollution either from rural (59 persons), or from
      urban environments (59 persons). Neither spontaneous rate of CAs (1.47% vs.
      1.69%) nor BLM-induced in vitro chromosomal breakage (0.79 vs. 0.83 break/cell)
      showed elevated rates when cytogenetic biomarkers of genotoxicity were compared
      between controls and exposed persons. Time spent in cleaning did not affect
      cytogenetic changes either (R(2) = 0.04). BLM-induced mutagen sensitivity was
      similar in exposed and control persons (27.1% vs. 30.5%). It seems that the red
      mud exposure does not appear to pose an immediate genotoxic hazard on residents
      when measured with cytogenetic methods. We recommend, however, that those
      involved in clean-up activities should be followed closely not only for overall
      health, but also for further genotoxic risk assessment, because the long-term
      hazards of ultra-fine fugitive dust particles with alkalinity of residual NaOH in
      red mud are still unknown.

PMID- 22987022
TI  - Safety of atomoxetine in combination with intravenous cocaine in cocaine
      experienced participants.
AB  - OBJECTIVES: Atomoxetine has been considered as an agonist replacement therapy for
      cocaine. We investigated the safety of the interaction of atomoxetine with
      cocaine and also whether cognitive function was affected by atomoxetine during
      short-term administration. METHODS: In a double-blind placebo-controlled
      inpatient study of 20 cocaine-dependent volunteers, participants received
      atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth
      and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in
      sequential daily sessions. RESULTS: Preinfusion mean systolic pressures showed a
      small but statistically significant difference between placebo and both doses of
      atomoxetine. Preinfusion mean diastolic pressures were significant between
      placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg
      cocaine was statistically significant only between the 80- and 100-mg atomoxetine
      doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS)
      scores for "bad effect" in the atomoxetine group were significantly higher at
      baseline, then declined, and for "likely to use" declined with atomoxetine
      treatment. On the Addiction Research Center Inventory, the atomoxetine group
      scored significantly lower on amphetamine, euphoria, and energy subscales (P <
      0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods
      State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did
      not affect cocaine pharmacokinetics. In tests of working memory, sustained
      attention, cognitive flexibility, and decision-making, atomoxetine improved
      performance on the visual n-back task. There were no differences in any
      pharmacokinetic parameters for cocaine with atomoxetine. CONCLUSIONS: Atomoxetine
      was tolerated safely by all participants. Certain cognitive improvements and a
      dampening effect on VAS scores after cocaine were observed, but should be weighed
      against small but significant differences in hemodynamic responses after
      atomoxetine.

PMID- 22987025
TI  - Long-term biomonitoring of breast cancer patients under adjuvant chemotherapy:
      the comet assay as a possible predictive factor.
AB  - Most chemotherapy treatments induce DNA damage in the exposed patients. Using the
      comet assay and peripheral blood mononuclear cells (PBMC), we have quantified
      this induced DNA damage and studied its relationship with GSTM1 and GSTT1
      polymorphisms, and clinical parameters. For this purpose, 29 Caucasian women,
      breast cancer patients under CMF or CEF adjuvant chemotherapy were included in
      the study. The clinical parameters considered were (i) therapies side effects,
      like haematological and biochemical toxicities, (ii) prognostic and predictive
      factors, like hormonal receptor expression, tumour differentiation degree,
      sickness stage, and nodal status, and (iii) the effectiveness of the chemotherapy
      measured as five years relapse probability. The results were also related to the
      confounding factor age. Comet assay results indicate that 13 patients were
      characterised by absence of induced DNA strand breaks, and 16 patients presented
      induced DNA strand breaks along the treatment. Relationships between comet
      variables and clinical parameters, found with principal component analysis,
      correlations, one-way ANOVA and multivariate logistic regression analyses
      revealed that: (1) baseline levels of DNA damage are related to GSTM1 genotype
      and to hormonal receptor expression; (2) GSTM1 genotype also influences comet
      results after chemotherapy, as it does the AST level; (3) the tail moment values
      of the cycle 6.1 and the sickness stage might predict cancer relapse at five
      years: for the Stage, OR = 13.8 (IIB versus I+IIA), 95% CI 0.80-238.97, and for
      6.1 cycle TM, OR = 1.3, 95%, CI 0.97-1.79, with a potential model (10* Stage (I
      IIA = 0, IIB = 1) + 6.1 cycle), that has a good predictive capacity, with an area
      under ROC curve of 0.872 (CI 0.62-1.00). To our knowledge, this is the first time
      such a predictive value is found for the comet assay. Nevertheless, before the
      comet assay could be used as a tool for oncologists, this relationship should be
      confirmed in more patients, and problems of standardisation and data
      interpretation should be solved.

PMID- 22987024
TI  - Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut
      Industrial Estate workers and nearby residents.
AB  - The Map-Ta-Phut Industrial Estate (MIE) in Rayong, Thailand, is the location of
      one of the largest industrial complexes in southeastern Asia. The MIE complex
      produces a mixture of air pollutants, including polycyclic aromatic hydrocarbons,
      compounds capable to induce the generation of DNA adducts. DNA adducts are
      considered to be a biomarker of carcinogen exposure; however, its production can
      be modulated by genetic susceptibility. Thus, we analysed the influence of EPHX1
      His139Arg (A>G, rs2234922) and NQO1 Pro187Ser (C>T, rs1800566) involved in the
      metabolism of polycyclic aromatic hydrocarbons; MnSOD(2) Val16Ala (C>T,
      rs1799725) a gene that acts against the free radical generation; APE1/Ref-1
      Asp148Glu (T>G, rs3136820) a gene involved in the repair of DNA, and in the
      control of cell-cycle and apoptosis on leucocyte DNA adducts in 77 MIE workers,
      69 Map-Ta-Phut residents, and 50 rural controls, Rayong, Thailand. We searched
      for associations with the 'sum of at-risk alleles' by combining the variant
      alleles of EPHX1, NQO1 and MnSOD(2) together with the wild-type allele of APE1,
      since they appeared to influence lung cancer risk. Although our findings revealed
      significant associations between DNA adducts and the EPHX1 His139Arg and NQO1
      Pro187Ser polymorphisms, the combination of at-risk alleles was found to affect
      DNA damage much stronger. DNA adducts were significantly increased in the
      individuals bearing 4 and >= 5 at-risk alleles [mean ratio (MR) = 1.55, 95% CI
      1.10-2.18, P = 0.012, and MR = 2.11, 95% CI 1.27-3.51, P = 0.004, respectively)].
      After correction for residence/employment categorisation, a significant increment
      was present in the MIE workers with >= 5 alleles (MR = 2.88, 95% CI 1.46-5.71, P
      = 0.003). Our data indicate relationships between the generation of DNA adducts
      and the enzymatic activities of EPHX and NQO1. The combination of unfavourable
      genetic variants seems to determine the individuals' susceptibility, rather than
      a single polymorphism.

PMID- 22987026
TI  - UVB irradiation changes genotoxic potential of nonylphenolpolyethoxylates-
      remarkable generation of gamma-H2AX with degradation of chemical structure.
AB  - Nonylphenolpolyethoxylates (NPEOs) are non-ionic surfactants widely used for
      industrial and household purposes. In actual environments, NPEOs can be
      biodegraded, but the products are reported to be more persistent and toxic than
      the parent compounds. NPEOs are also exposed to sunlight and degraded. Studies on
      the photodegradation of NPEOs have focused mainly on chemical changes after
      exposure to light. Toxic changes of photodegraded products correlating to the
      chemical changes are not completely understood. In this study, we examined the
      genotoxicity of UVB-irradiated NPEOs having ethylene oxide units 15 and 70 in a
      human breast adenocarcinoma cell line, MCF-7, based on the phosphorylation of
      histone H2AX (gamma-H2AX), a sensitive marker for DNA damage. We clarified that
      UVB irradiation drastically changed the genotoxic potential of NPEOs: NPEO(15)'s
      ability to generate gamma-H2AX was significantly reduced, whereas non-genotoxic
      NPEO(70) became able to generate gamma-H2AX. Flow cytometric analysis showed that
      the gamma-H2AX generated by UVB-irradiated NPEO(70)was produced independent of
      cell cycle phases. In addition, its production involved the activation of ATM or
      DNA-PK, a general signalling pathway in response to DNA double strand breaks.
      High-performance liquid chromatography analysis indicated that the formation of
      NPEO intermediates with a short side-chain like NPEO(15) was the cause of the
      gamma-H2AX generation. This study suggests the importance of taking the
      genotoxicity of photodegraded intermediates into consideration when conducting
      risk assessments of environmental pollutants.

PMID- 22987027
TI  - Molecular characterisation of murine acute myeloid leukaemia induced by 56Fe ion
      and 137Cs gamma ray irradiation.
AB  - Exposure to sparsely ionising gamma- or X-ray irradiation is known to increase
      the risk of leukaemia in humans. However, heavy ion radiotherapy and extended
      space exploration will expose humans to densely ionising high linear energy
      transfer (LET) radiation for which there is currently no understanding of
      leukaemia risk. Murine models have implicated chromosomal deletion that includes
      the hematopoietic transcription factor gene, PU.1 (Sfpi1), and point mutation of
      the second PU.1 allele as the primary cause of low-LET radiation-induced murine
      acute myeloid leukaemia (rAML). Using array comparative genomic hybridisation,
      fluorescence in situ hybridisation and high resolution melt analysis, we have
      confirmed that biallelic PU.1 mutations are common in low-LET rAML, occurring in
      88% of samples. Biallelic PU.1 mutations were also detected in the majority of
      high-LET rAML samples. Microsatellite instability was identified in 42% of all
      rAML samples, and 89% of samples carried increased microsatellite mutant
      frequencies at the single-cell level, indicative of ongoing instability.
      Instability was also observed cytogenetically as a 2-fold increase in chromatid
      type aberrations. These data highlight the similarities in molecular
      characteristics of high-LET and low-LET rAML and confirm the presence of ongoing
      chromosomal and microsatellite instability in murine rAML.

PMID- 22987028
TI  - Implication of gluconate kinase activity in L-ornithine biosynthesis in
      Corynebacterium glutamicum.
AB  - With the purpose of generating a microbial strain for L-ornithine production in
      Corynebacterium glutamicum, genes involved in the central carbon metabolism were
      inactivated so as to modulate the intracellular level of NADPH, and to evaluate
      their effects on L-ornithine production in C. glutamicum. Upon inactivation of
      the 6-phosphoglucoisomerase gene (pgi) in a C. glutamicum strain, the concomitant
      increase in intracellular NADPH concentrations from 2.55 to 5.75 mmol g-1 (dry
      cell weight) was accompanied by reduced growth rate and L-ornithine production,
      suggesting that L-ornithine production is not solely limited by NADPH
      availability. In contrast, inactivation of the gluconate kinase gene (gntK) led
      to a 51.8 % increase in intracellular NADPH concentration, which resulted in a
      49.9 % increase in L-ornithine production. These results indicate that excess
      NADPH is not necessarily rate-limiting, but is required for increased L-ornithine
      production in C. glutamicum.

PMID- 22987030
TI  - The new science of oxide interfaces.

PMID- 22987029
TI  - Impact of the 2008 US Preventive Services Task Force recommendation to
      discontinue prostate cancer screening among male Medicare beneficiaries.

PMID- 22987031
TI  - Magnetoelectric interfaces and spin transport.
AB  - Engineered heterostructures designed for electric control of magnetic properties,
      the so-called magnetoelectric interfaces, present a novel route towards using the
      spin degree of freedom in electronic devices. Here, we review how a subset of
      such interfaces, namely ferromagnet-ferroelectric heterostructures, display
      electronically mediated control of magnetism and, in particular, emphasis is
      placed on how these effects manifest themselves as detectable spin-dependent
      transport phenomena. Examples of these effects are given for a variety of
      material systems on the basis of ferroelectric oxides, manganese and ruthenium
      magnetic complex oxides and elemental ferromagnetic metals. Results from both
      theory and experiment are discussed.

PMID- 22987032
TI  - Emergent phenomena at multiferroic heterointerfaces.
AB  - The coupling and reconstruction of electronic degrees of freedom (such as charge,
      spin and orbital) at a heterointerface can lead to unexpected and exotic states
      of matter. In this study, using model systems consisting of multiferroic BiFeO(3)
      and ferromagnetic La(0.7)Sr(0.3)MnO(3), we review the current understanding of a
      novel interfacial magnetic state formed at the interface, and highlight some
      possible mechanisms responsible for this interesting phenomenon and identify open
      questions for future studies.

PMID- 22987033
TI  - Reliable polarization switching of BiFeO3.
AB  - As a room temperature multi-ferroic with coexisting anti-ferromagnetic,
      ferroelectric and ferroelastic orders, BiFeO(3) has been extensively studied to
      realize magnetoelectric devices that enable manipulation of magnetic ordering by
      an electric field. Moreover, BiFeO(3) is a promising candidate for ferroelectric
      memory devices because it has the largest remanent polarization (P(r)>100 MUC cm(
      2)) of all ferroelectric materials. For these applications, controlling
      polarization switching by an electric field plays a crucial role. However,
      BiFeO(3) has a complex switching behaviour owing to the rhombohedral symmetry:
      ferroelastic (71 degrees , 109 degrees ) and ferroelectric (180 degrees )
      switching. Furthermore, the polarization is switched through a multi-step
      process: 180 degrees  switching occurs through three sequential 71 degrees 
      switching steps. By using monodomain BiFeO(3) thin-film heterostructures, we
      correlated such multi-step switching to the macroscopically observed reliability
      issues of potential devices such as retention and fatigue. We overcame the
      retention problem (i.e. elastic back-switching of the 71 degrees  switched area)
      using monodomain BiFeO(3) islands. Furthermore, we suppressed the fatigue problem
      of 180 degrees  switching, i.e. loss of switchable polarization with switching
      cycles, using a single 71 degrees  switching path. Our results provide a
      framework for exploring a route to reliably control multiple-order parameters
      coupled to ferroelastic order in other rhombohedral and lower-symmetry materials.

PMID- 22987034
TI  - Insights from the study of high-temperature interface superconductivity.
AB  - A brief overview is given of the studies of high-temperature interface
      superconductivity based on atomic-layer-by-layer molecular beam epitaxy (ALL
      MBE). A number of difficult materials science and physics questions have been
      tackled, frequently at the expense of some technical tour de force, and sometimes
      even by introducing new techniques. ALL-MBE is especially suitable to address
      questions related to surface and interface physics. Using this technique, it has
      been demonstrated that high-temperature superconductivity can occur in a single
      copper oxide layer-the thinnest superconductor known. It has been shown that
      interface superconductivity in cuprates is a genuine electronic effect-it arises
      from charge transfer (electron depletion and accumulation) across the interface
      driven by the difference in chemical potentials rather than from cation diffusion
      and mixing. We have also understood the nature of the superconductor-insulator
      phase transition as a function of doping. However, a few important questions,
      such as the mechanism of interfacial enhancement of the critical temperature, are
      still outstanding.

PMID- 22987035
TI  - Termination control of electronic phases in oxide thin films and interfaces:
      LaAlO3/SrTiO3(001).
AB  - A wealth of intriguing properties emerge in the seemingly simple system composed
      of the band insulators LaAlO(3) and SrTiO(3) such as a two-dimensional electron
      gas, superconductivity and magnetism. In this paper, we review the current
      insight obtained from first principles calculations on the mechanisms governing
      the behaviour of thin LaAlO(3) films on SrTiO(3)(001). In particular, we explore
      the strong dependence of the electronic properties on the surface and interface
      termination, the finite film thickness, lattice polarization and defects. A
      further aspect that is addressed is how the electronic behaviour and
      functionality can be tuned by an SrTiO(3) capping layer, adsorbates and metallic
      contacts. Lastly, we discuss recent reports on the coexistence of magnetism and
      superconductivity in this system for what they might imply about the electronic
      structure of this system.

PMID- 22987036
TI  - Cationic-vacancy-induced room-temperature ferromagnetism in transparent,
      conducting anatase Ti1-xTaxO2 (x~0.05) thin films.
AB  - We report room-temperature ferromagnetism (FM) in highly conducting, transparent
      anatase Ti(1-x)Ta(x)O(2) (x~0.05) thin films grown by pulsed laser deposition on
      LaAlO(3) substrates. Rutherford backscattering spectrometry (RBS), X-ray
      diffraction, proton-induced X-ray emission, X-ray absorption spectroscopy (XAS)
      and time-of-flight secondary-ion mass spectrometry indicated negligible magnetic
      contaminants in the films. The presence of FM with concomitant large carrier
      densities was determined by a combination of superconducting quantum interference
      device magnetometry, electrical transport measurements, soft X-ray magnetic
      circular dichroism (SXMCD), XAS and optical magnetic circular dichroism, and was
      supported by first-principles calculations. SXMCD and XAS measurements revealed a
      90 per cent contribution to FM from the Ti ions, and a 10 per cent contribution
      from the O ions. RBS/channelling measurements show complete Ta substitution in
      the Ti sites, though carrier activation was only 50 per cent at 5 per cent Ta
      concentration, implying compensation by cationic defects. The role of the Ti
      vacancy (V(Ti)) and Ti(3+) was studied via XAS and X-ray photoemission
      spectroscopy, respectively. It was found that, in films with strong FM, the V(Ti)
      signal was strong while the Ti(3+) signal was absent. We propose (in the absence
      of any obvious exchange mechanisms) that the localized magnetic moments, V(Ti)
      sites, are ferromagnetically ordered by itinerant carriers. Cationic-defect
      induced magnetism is an alternative route to FM in wide-band-gap semiconducting
      oxides without any magnetic elements.

PMID- 22987037
TI  - Giant flexoelectric effect through interfacial strain relaxation.
AB  - Interfacial strain gradients in oxide epitaxial thin films provide an interesting
      opportunity to study flexoelectric effects and their potential applications.
      Oxide epitaxial thin films can exhibit giant and tunable flexoelectric effects,
      which are six or seven orders of magnitude larger than those in conventional bulk
      solids. The strain gradient in an oxide epitaxial thin film can generate an
      electric field above 1 MV m(-1) by flexoelectricity, large enough to affect the
      physical properties of the film. Giant flexoelectric effects on ferroelectric
      properties are discussed in this overview of recent experimental observations.

PMID- 22987038
TI  - Towards electrical spin injection into LaAlO3-SrTiO3.
AB  - Future spintronics devices will be built from elemental blocks allowing the
      electrical injection, propagation, manipulation and detection of spin-based
      information. Owing to their remarkable multi-functional and strongly correlated
      character, oxide materials already provide such building blocks for charge-based
      devices such as ferroelectric field-effect transistors (FETs), as well as for
      spin-based two-terminal devices such as magnetic tunnel junctions, with giant
      responses in both cases. Until now, the lack of suitable channel materials and
      the uncertainty of spin-injection conditions in these compounds had however
      prevented the exploration of similar giant responses in oxide-based lateral spin
      transport structures. In this paper, we discuss the potential of oxide-based spin
      FETs and report magnetotransport data that suggest electrical spin injection into
      the LaAlO(3)-SrTiO(3) interface system. In a local, three-terminal measurement
      scheme, we analyse the voltage variation associated with the precession of the
      injected spin accumulation driven by perpendicular or longitudinal magnetic
      fields (Hanle and 'inverted' Hanle effects). The spin accumulation signal appears
      to be much larger than expected, probably owing to amplification effects by
      resonant tunnelling through localized states in the LaAlO(3). We give
      perspectives on how to achieve direct spin injection with increased detection
      efficiency, as well on the implementation of efficient top gating schemes for
      spin manipulation.

PMID- 22987039
TI  - Phase engineering in oxides by interfaces.
AB  - Optical second harmonic generation and piezoresponse force microscopy are used to
      investigate manifestations of ordered states directly related to the presence of
      an oxide interface. Three examples, each with a very different scope, are
      reviewed in order to highlight the richness of interface-related phenomena in
      oxides. (i) The orbital states involved in the emergence of an interfacial
      conducting state in LaAlO(3)/SrTiO(3) heterostructures are investigated, which
      reveal a surprising decoupling of orbital and transport properties; (ii) the
      distribution of ferroelectric and antiferromagnetic domains in epitaxial films of
      the multiferroic hexagonal manganites is investigated, which reveals striking
      differences to the corresponding bulk crystals; and (iii) the distribution of
      trimerization-polarization domains in the hexagonal manganites is investigated,
      which reveals the presence of topologically protected domain walls with
      properties different from the bulk.

PMID- 22987040
TI  - Laparoscopic versus open Kasai portoenterostomy in infant with biliary atresia: a
      retrospective review on the 5-year native liver survival.
AB  - PURPOSE: Laparoscopic Kasai portoenterostomy was reported to be a safe and
      feasible procedure in infant with biliary atresia. We aimed to investigate the
      long-term results after laparoscopic portoenterostomy as such data in the
      literature are lacking. METHODS: Sixteen infants underwent laparoscopic Kasai
      portoenterostomy from 2002 to 2006. The age and the sex of the patient, the
      bilirubin level before the operation, the early clearance of jaundice (total
      bilirubin <20 MUmol/L within 6 months of portoenterostomy), the native liver
      survival at 2 and 5 years after the operation were reviewed. The results were
      retrospectively compared with 16 consecutive infants who underwent open Kasai
      portoenterostomy before 2002. RESULTS: All infants had type III biliary atresia.
      The early clearance of jaundice rate at 6 months was 50 % (8/16) after
      laparoscopic operation and was 75 % (12/16) after open operation (p = 0.144). Two
      years after the operation, the native liver survival was 50 % (8/16) in the
      laparoscopic group and was 81 % (13/16) in the open group (p = 0.076). Five years
      after the operation, the native liver survival rate was 50 % (8/16) in the
      laparoscopic group and was 81 % (13/16) in the open group (p = 0.076). The
      jaundice-free native liver survival rate at 5 years was 50 % (8/16) in
      laparoscopic group and was 75 % (12/16) in the open group. In the laparoscopic
      group, all patients with early clearance of jaundice survived and remained
      jaundice freed 5 years after the operation. CONCLUSION: The 5-year native liver
      survival rate after laparoscopic portoenterostomy was 50 %. Apparently superior
      result was observed in the open group (81 %) although the figures did not reach
      statistical difference because of the small sample size. A larger scale study is
      required to draw a more meaningful conclusion.

PMID- 22987041
TI  - The interaction between obesity and RAGE polymorphisms on the risk of knee
      osteoarthritis in Chinese population.
AB  - BACKGROUND: The receptor for advanced glycation end products (RAGE) has been
      reported to relate to osteoarthritis (OA), however, the role of RAGE genetic
      variants in OA remains unknown. METHOD: A total of 233 patients with primary knee
      OA and 255 healthy volunteer were recruited. Three RAGE gene polymorphisms,
      namely, Gly82Ser (rs2070600). -374T/A (rs1800624) and 429T/C (rs1800625) were
      genotyped. RESULTS: Of all three RAGE gene polymorphisms, only the genotype
      distributions and alleles frequencies of 82G/S polymorphisms significantly
      differed between knee OA and control subjects. The presence of SS genotype and S
      allele of 82G/S we significantly higher in knee OA subjects than in controls
      (34.76% vs. 19.61%, P for trend =0.004; 57.64% vs. 48.59%, P for trend <0.001,
      respectively). Multivariate logistic regression analysis showed a significantly
      increased risk for knee OA for the SS genotype compared with the AA genotype (OR=
      1.984, 95% CI: 1.238-3.181; P =0.004). The adjusted OR for S allele carriage was
      significantly higher than G allele carriage (OR=1.440, 95% CI: 1.137-1.8231,
      P=0.002). Moreover, a significant multiplicative interaction was observed between
      82G/S polymorphisms with obesity (Pinteraction=0.028). Taking the non-obese 82GG
      genotype as references, the OR for OA in non-obese SS carriers was 2.537 (95% CI
      1.241-5.189, P=0.001). Notably, the OR in obese GS carriers was 2.304 (95% CI:
      1.218-4.357, P=0.009) and in obese SS was 3.392 (95% CI: 1.672-6.885, P=0.001).
      The -374T/A and -429T/C did not show positive interaction with obesity and
      smoking status. CONCLUSION: The AGE 82G/S polymorphisms, in interaction with
      obesity, may determine the susceptibility of OA in Chinese population.

PMID- 22987042
TI  - Amyloid-beta induced signaling by cellular prion protein and Fyn kinase in
      Alzheimer disease.
AB  - Alzheimer disease (AD) is the most prevalent cause of dementia. Amyloid-beta
      (Abeta) oligomers are potent synaptotoxins thought to mediate AD-related
      phenotypes. Cellular prion protein (PrP(C)) has been identified as a high
      affinity receptor for Abeta oligomers. Herein, we review the functional
      consequences of Abeta oligomer binding to PrP(C) on the neuronal surface. We
      highlight recent evidence that Fyn kinase mediates signal transduction downstream
      of the PrP(C)-Abeta oligomer complex. These studies suggest that PrP(C) has a
      central role in AD pathogenesis and may provide a target for therapeutic
      intervention in AD.

PMID- 22987043
TI  - Intersection of inflammation and herbal medicine in the treatment of
      osteoarthritis.
AB  - Herbal remedies and dietary supplements have become an important area of research
      and clinical practice in orthopaedics and rheumatology. Understanding the risks
      and benefits of using herbal medicines in the treatment of arthritis, rheumatic
      diseases, and musculoskeletal complaints is a key priority of physicians and
      their patients. This review discusses the latest advances in the use of herbal
      medicines for treating osteoarthritis (OA) by focusing on the most significant
      trends and developments. This paper sets the scene by providing a brief
      introduction to ethnopharmacology, Ayurvedic medicine, and nutrigenomics before
      discussing the scientific and mechanistic rationale for targeting inflammatory
      signalling pathways in OA by use of herbal medicines. Special attention is drawn
      to the conceptual and practical difficulties associated with translating data
      from in-vitro experiments to in-vivo studies. Issues relating to the low
      bioavailability of active ingredients in herbal medicines are discussed, as also
      is the need for large-scale, randomized clinical trials.

PMID- 22987044
TI  - New dyads using (metallo)porphyrins as ancillary ligands in polypyridine
      ruthenium complexes. Synthesis and electronic properties.
AB  - Porphyrins bearing enaminoketones at their periphery have been used as ancillary
      ligands in ruthenium complexes. Free base, nickel and zinc porphyrins were
      successfully coordinated to Ru(bpy)(2)Cl(2) under microwave irradiation. The
      positive contribution of the ruthenium complex was demonstrated by the complexes'
      wide absorption domains that covered the 500-600 nm region where the parent
      porphyrins did not absorb. Electrochemical as well as computational data revealed
      an efficient electronic communication between the porphyrins and the ruthenium
      cation in the dyads.

PMID- 22987045
TI  - The meta-analysis of the association of PPARG P12A, C161T polymorphism and
      coronary heart disease.
AB  - OBJECTIVE: Two common variations of peroxisome proliferator-activated receptor
      gamma (PPARG), P12A (Pro12Ala, rs1801282), and C161T (His447His, rs3856806), are
      thought to have an effect on susceptibility to coronary heart disease (CHD), but
      the results are inconsistent. Therefore, a meta-analysis of published studies was
      performed. METHODS: The electronic databases, PubMed, Embase, Web of Science, and
      CNKI (China National Knowledge Infrastructure) were searched for studies to
      include in the present meta-analysis (last search was updated on 30 Aug. 2011).
      Twenty studies testing the association between PPARG gene polymorphisms and CHD
      were examined: 12 studies of P12A; 8 studies of C161T. Overall and ethnicity
      specific summary odds ratios and corresponding 95 % confidence intervals for CHD
      associated with these polymorphisms were estimated using fixed- and random
      effects models. Heterogeneity and publication bias were evaluated. A total of 20
      studies including 5,795 cases and 9,069 controls were included in this meta
      analysis. RESULTS: No significant associations were found in carriers of the rare
      Ala allele of the P12A polymorphism versus the common Pro/Pro genotype among the
      studies with both of the fixed-effect and random-effect model. In the subgroup
      analyses by ethnicity, source of control and type of study, no significant risks
      were found. For PPARG C161T, carriers of the T variant of C161T polymorphism were
      associated with an increased risk of CHD (OR = 1.182, 95 % CI: 1.023-1.341,
      P(heterogeneity) = 0.002), and in the stratified analysis by ethnicity and source
      of controls, the contrast of CT + TT vs. CC all produced significant association
      in Asian and hospital-based controls (OR = 1.276, 95 % CI: 1.084-1.468,
      P(heterogeneity) = 0.055; OR = 1.164, 95 % CI: 1.001-1.326, P(heterogeneity) =
      0.002),when the fixed-effect model was used. But they were all insignificant with
      the random-effect model. CONCLUSION: This meta-analysis suggests that the PPARG
      C161T polymorphism marginally contributes to increased susceptibility to CHD and
      marginally increased association between PPARG H477H polymorphism and CHD also
      appeared in Asian and hospital-based controls. But PPARG P12A polymorphism is not
      associated with CHD risk.

PMID- 22987048
TI  - Creativity and psychiatric illness: the search for a missing link--an historical
      context for current research.
AB  - Creativity is an important human quality upon which many achievements of
      humankind are based. Defined as the ability to produce something that is novel
      and useful or meaningful, it is difficult to operationalize for research. This
      text provides an overview of the historical and cultural context of this
      research. The assumption that creativity is related to psychiatric vulnerability
      dates back to antiquity. The modern interest in the subject stems from the
      romantic era and gained a scientific aura in the 19th century. In the 20th
      century, a further entanglement of creativity and psychopathology came about
      through the influence of patient artists on regular art. Psychometric,
      psychodiagnostic and genetic research supports a connection between creativity
      and psychiatric illness within the bipolar-psychotic continuum, with
      schizotypy/thymotypy as prototypes of creativity-related disorders. Evolutionary
      hypotheses link the schizophrenia paradox to a survival advantage through
      enhanced creative ability. The relevance of scientific research in this complex
      and heterogeneous area can be increased if creativity and psychopathology are
      further operationalized and if underlying art concepts are made explicit and
      placed in a broader cultural context. There is a continuing need for meaningful
      definitions and measures, as well as a multidisciplinary collaboration.

PMID- 22987049
TI  - Management of the open abdomen during the global war on terror.
AB  - OBJECTIVE: To evaluate factors that are predictive of delayed abdominal closure
      in patients injured during military conflict. DESIGN, SETTING, AND PATIENTS:
      Seventy-one patients managed with an open abdomen were identified from records at
      Landstuhl Regional Medical Center from 2005 and 2006. Follow-up data were
      available from Walter Reed Army Medical Center. Records were reviewed through all
      echelons of care. Ordinal logistic regression was used to predict delayed
      abdominal closure. RESULTS: Patients sustained injury from blunt (n = 2),
      penetrating (n = 30), and blast (n = 39) mechanisms. The median Injury Severity
      Score was 25 (interquartile range, 17-34). Abdominal injury was observed in 85%
      of patients, and 48% underwent a massive transfusion. The median time to transfer
      to the United States was 5.3 days (interquartile range, 4.3-6.8 days). Abdomens
      were definitively closed downrange (11%), at Landstuhl Regional Medical Center
      (33%), or at Walter Reed Army Medical Center (56%). The median time until
      abdominal closure was 13 days (interquartile range, 4-40 days) in 2005 compared
      with 4 days (interquartile range, 1-14.5 days) in 2006 (P = .02). The
      multivariate model identified massive transfusion (odds ratio, 3.9), presence of
      complications (odds ratio, 5.1), and an injury date in 2005 (odds ratio, 3.4) as
      independently predictive variables for later abdominal closure. CONCLUSIONS:
      Massive transfusion, occurrence of complications, and earlier injury date were
      predictive of delayed abdominal closure in casualties managed with an open
      abdomen. These data suggest an evolving approach to the management of severely
      injured combat casualties that involves earlier abdominal closure.

PMID- 22987047
TI  - Combinatorial Synthesis of and high-throughput protein release from polymer film
      and nanoparticle libraries.
AB  - Polyanhydrides are a class of biomaterials with excellent biocompatibility and
      drug delivery capabilities. While they have been studied extensively with
      conventional one-sample-at-a-time synthesis techniques, a more recent high
      throughput approach has been developed enabling the synthesis and testing of
      large libraries of polyanhydrides(1). This will facilitate more efficient
      optimization and design process of these biomaterials for drug and vaccine
      delivery applications. The method in this work describes the combinatorial
      synthesis of biodegradable polyanhydride film and nanoparticle libraries and the
      high-throughput detection of protein release from these libraries. In this
      robotically operated method (Figure 1), linear actuators and syringe pumps are
      controlled by LabVIEW, which enables a hands-free automated protocol, eliminating
      user error. Furthermore, this method enables the rapid fabrication of micro-scale
      polymer libraries, reducing the batch size while resulting in the creation of
      multivariant polymer systems. This combinatorial approach to polymer synthesis
      facilitates the synthesis of up to 15 different polymers in an equivalent amount
      of time it would take to synthesize one polymer conventionally. In addition, the
      combinatorial polymer library can be fabricated into blank or protein-loaded
      geometries including films or nanoparticles upon dissolution of the polymer
      library in a solvent and precipitation into a non-solvent (for nanoparticles) or
      by vacuum drying (for films). Upon loading a fluorochrome-conjugated protein into
      the polymer libraries, protein release kinetics can be assessed at high
      throughput using a fluorescence-based detection method (Figures 2 and 3) as
      described previously(1). This combinatorial platform has been validated with
      conventional methods(2) and the polyanhydride film and nanoparticle libraries
      have been characterized with (1)H NMR and FTIR. The libraries have been screened
      for protein release kinetics, stability and antigenicity; in vitro cellular
      toxicity, cytokine production, surface marker expression, adhesion, proliferation
      and differentiation; and in vivo biodistribution and mucoadhesion(1-11). The
      combinatorial method developed herein enables high-throughput polymer synthesis
      and fabrication of protein-loaded nanoparticle and film libraries, which can, in
      turn, be screened in vitro and in vivo for optimization of biomaterial
      performance.

PMID- 22987051
TI  - Endothelin(A)-endothelin(B) receptor cross talk in endothelin-1-induced
      contraction of smooth muscle.
AB  - The efficacy of selective endothelin (ET) receptor antagonists may be limited by
      a functional interaction between the ET(A) and ET(B) receptors. This interaction,
      also termed "cross talk", is characterized by the dependency of the inhibition of
      an ET-1 response due to antagonism of one ET receptor subtype upon concomitant
      antagonism of the other ET receptor subtype. Although a reduction in ET(A)-ET(B)
      receptor cross talk would presumably increase the efficacy of selective ET
      receptor antagonists, an approach that accomplishes this aim is largely absent
      due to a lack of mechanistic understanding. Toward this goal, we evaluated the
      characteristics and potential dependencies of cross talk in smooth muscle. Smooth
      muscle was adopted as an exemplar not only because cross talk is widely reported
      in this tissue type, thereby allowing numerous comparisons, but also significant
      controversy surrounds the use of selective versus nonselective ET receptor
      antagonists in ET-1-related pathophysiologies involving smooth muscle. Based on
      this evaluation, we suggest that ET(A)-ET(B) receptor cross talk is a dynamic
      process directed by either or both ET receptor subtypes and expressed to varying
      magnitudes depending on the ET-1 and selective ET receptor antagonist
      concentrations, tone due to intraluminal pressure/stretch, agonists acting at
      receptors other than the ET(A)/ET(B) receptors, and endothelial/epithelial
      function. It is speculated that ET(A)-ET(B) receptor cross talk occurs through
      signal transduction pathways along with changes at the receptor level.
      Pharmacologic intervention of the signaling pathways could increase the
      therapeutic efficacy of ET receptor antagonists.

PMID- 22987052
TI  - The effect of clonidine, an alpha-2 adrenergic receptor agonist, on inflammatory
      response and postischemic endothelium function during early reperfusion in
      healthy volunteers.
AB  - Ischemia-reperfusion disturbs endothelial physiology and generates a
      proinflammatory state. Animal studies showed that clonidine administered prior
      hypoxia improves posthypoxic endothelial function. To investigate this effect in
      human, we have assessed the postischemic endothelium function and the
      proinflammatory state in healthy volunteers with and without clonidine. Seven
      volunteers were included. Each subject underwent the experimental protocol (15
      minutes nondominant forearm ischemia) with and without clonidine. Endothelial
      function was assessed by flow-mediated dilatation (FMD) in the brachial artery
      before ischemia (FMDPI), immediately after ischemia (FMDIAI), and 15 minutes
      after ischemia (FMD15AI). Neutrophil (CD11b/CD18) and platelet (CD42b)
      activations were measured by flow cytometry during reperfusion in blood samples
      from ischemic (local) and nonischemic (systemic) forearms. Proinflammatory state
      was assessed by serum concentration of interleukin (IL)-1beta and -6. Clonidine
      does not influence baseline FMD (P = 0.118) but improves FMDIAI (P = 0.018) and
      FMD15AI (P = 0.018). It increases platelet activation in systemic circulation (P
      = 0.003) during reperfusion but not in local circulation (P = 0.086). Clonidine
      increases neutrophil activation in local circulation (P = 0.001) but not in
      systemic circulation (P = 0.642). In local circulation, clonidine decreases IL-6
      (P = 0.044) but does not influence IL-1beta (P = 0.113). By contrast, it
      decreases both IL-6 (P = 0.026) and IL-1beta (P = 0.027) concentrations in
      systemic circulation. In conclusion, clonidine improves endothelial function and
      modulates inflammation during reperfusion.

PMID- 22987053
TI  - Influence of simvastatin on the thromboxane and prostacyclin pathways, in vitro
      and in vivo.
AB  - 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) are
      believed to exert beneficial effects against cardiovascular disease beyond
      correction of dyslipidemia. The aim of this combined in vitro and in vivo study
      was to investigate the influence of the commonly used simvastatin on prostacyclin
      and thromboxane A2, 2 prostaglandins with different cardiovascular effects,
      normally in homeostatic balance in the circulatory system. Single-dose
      administration of simvastatin significantly decreased urinary prostacyclin
      excretion of healthy volunteers (P < 0.01) and increased the ratio between
      thromboxane A2 and prostacyclin (2-fold increase, P < 0.01), as assessed by
      enzyme immunoassays of the corresponding metabolites in urine. Human vascular
      endothelial cells, exposed to corresponding concentrations of simvastatin and
      assayed in the same way, reduced the release of prostacyclin about 40% (P <
      0.05), altered the transcriptional expression of cyclooxygenase and prostacyclin
      synthase as analyzed by real-time polymerase chain reaction, and reduced the
      prostacyclin synthase promoter activity by 50% (P < 0.05), evaluated in a
      luciferase reporter system. We speculate that simvastatin shifts the balance
      between thromboxane A2 and prostacyclin in favor of the thromboxane pathway in
      vivo, and after exposure to clinically relevant concentrations in vitro. This may
      have pathophysiological implications by promoting a prothrombotic state in the
      blood vessels.

PMID- 22987054
TI  - Effects of valsartan on cardiovascular morbidity and mortality in high-risk
      hypertensive patients with new-onset diabetes mellitus.
AB  - BACKGROUND:  The KYOTO HEART Study demonstrated that Valsartan Add-on treatment
      was effective to reduce new-onset diabetes in high-risk hypertensive patients.
      The purpose of the present study was to examine the effects of Valsartan Add-on
      treatment on cardiovascular (CV) events in patients with or without diabetes.
      METHODS AND RESULTS:  A total of 3,031 patients were divided at baseline:
      Baseline Diabetes (n=807) and Baseline Non-Diabetes (n=2,224). Among the Non
      Diabetes patients, 144 developed diabetes (New-Onset Diabetes) and the remaining
      patients did not throughout the study (Final Non-Diabetes, n=2,080). Baseline
      Diabetes showed significantly higher CV event rates than Baseline Non-Diabetes
      (10.3% vs. 7.0%, P=0.00400). Valsartan Add-on treatment significantly reduced CV
      event rates than Non-angiotensin receptor blocker (ARB) treatment both in
      Baseline Diabetes (6.7% vs. 13.8%, P=0.00274) and in Baseline Non-Diabetes (5.0%
      vs. 8.9%, P=0.00036), respectively. New-Onset Diabetes showed a similar CV event
      rate (12.5%) to Baseline Diabetes (10.3%) but the event rate was significantly
      higher than that of Final Non-Diabetes (6.6%, P=0.0065). In the New-Onset
      Diabetes, Valsartan add-on treatment significantly reduced CV event rate than Non
      ARB treatment (5.2% vs. 17.4%, P=0.04601). CONCLUSIONS:  CV event risk in New
      Onset Diabetes was relatively equivalent to Baseline Diabetes. Valsartan Add-on
      treatment was effective for the reduction of CV events not only in Baseline
      Diabetes but also in New-Onset Diabetes.

PMID- 22987056
TI  - Modulation of antioxidant enzyme expression by PTU-induced hypothyroidism in
      cerebral cortex of postnatal rat brain.
AB  - This study aimed to elucidate the effect of 6-n-propylthiouracil (PTU)-induced
      hypothyroidism on oxidative stress parameters and expression of antioxidant
      enzymes in cerebral cortex of rat brain during postnatal development. A
      significant decrease in levels of lipid peroxidation and H(2)O(2) were seen in 7
      and 30 days old PTU-treated rats with respect to their controls. Significantly
      decreased activities of superoxide dismutase (SOD) and catalase (CAT) along with
      the translated products of SOD1 and SOD2 were observed in 7, 15 and 30 days old
      PTU-treated rats as compared to their respective controls. However, increase in
      translated product of CAT was seen in all age groups of PTU-treated rats.
      Glutathione peroxidase activity was decreased in 7 days and increased in 15 days
      old PTU-treated rats with respect to their control groups. Histological sections
      clearly show a decline in neuronal migration with neurons packed together in the
      hypothyroid group as compared to the control.

PMID- 22987055
TI  - The causal role of megakaryocyte-platelet hyperactivity in acute coronary
      syndromes.
AB  - Platelets are causally involved in coronary artery obstruction in acute coronary
      syndromes (ACS). This cell type is unique to mammals and its production, which is
      unlike that of any other mammalian cell, involves polyploid nuclear change in the
      mother cell (megakaryocyte) and the production of anucleate cells with a log
      Gaussian distribution of volume. Platelets vary more in cellular volume than any
      other circulating blood element in mammals. Larger platelets are denser, contain
      more secretory granules, and are more reactive than their smaller counterparts. A
      causal relationship between the presence of large, dense, reactive platelets in
      the circulation and ACS is supported by many clinical studies. Furthermore, the
      results of two large, prospective, epidemiological studies have demonstrated that
      mean platelet volume was the strongest independent predictor of outcome in
      patients with acute myocardial infarction. Notably, evidence indicates that an
      increase in mean platelet volume in the pathogenesis of ACS can potentially
      overwhelm current therapeutics. The control system for the physiological and
      pathophysiological production of large platelets should, therefore, be
      researched. An understanding of this system might give rise to new therapeutics
      that could control platelet reactivity and thereby comprehensively prevent ACS.

PMID- 22987058
TI  - Regulation of ERalpha protein expression by 17beta-estradiol in cultured neurons
      of hypothalamic ventromedial nucleus.
AB  - The activation of the subtype alpha of estrogen receptors (ERalpha) in the
      hypothalamic ventromedial nucleus (VMNvl) is required to stimulate female sexual
      receptivity. Moreover, the hormone was found to govern the expression of the
      receptor. Its removal due to ovariectomy and subsequent substitution suggest that
      the hormone down-regulates the expression of ERalpha. In contrast, in normally
      cycling animals the expression of the receptor peaks at proestrus, the phase of
      highest concentration of 17beta-estradiol in estrous cycle. Therefore, in this
      study we examined the influence of the hormone on ERalpha expression in primary
      dissociated cultures of neurons isolated from the VMNvl of young adult female
      rats. Measurements of ERalpha immunofluorescence revealed that both
      supraphysiological and physiological concentrations of 17beta-estradiol increase
      the expression of ERalpha. Analyses with selective agonists showed that both
      nuclear ERs are able to mediate the action of the hormone. However, the
      activation of ERalpha had a stronger effect on the expression of its own receptor
      than the activation of ERbeta. Simultaneous activation of both receptors
      attenuated the influence of ERalpha alone. Physiological concentrations of
      progesterone were found to revoke the effect of 17beta-estradiol, whereas the
      expression of ERalpha is up-regulated by progesterone alone. These data indicate
      that the expression of ERalpha in VMNvl neurons is under the control of both
      types of nuclear ERs and, in addition, progesterone receptors (PRs). The
      particular contribution of the receptors is dependent on their level of
      expression and the hormonal context. In neurons expressing high quantity of
      ERalpha, ERbeta attenuates the overall expression of the receptor, whereas in
      cells containing mostly ERbeta it contributes to the up-regulation of ERalpha
      synthesis. Simultaneous activation of ERs and PRs reverses the influences of the
      receptors due to inter-inhibition of their transcriptional activities.

PMID- 22987057
TI  - Effects of transient cerebral ischemia on the expression of DNA methyltransferase
      1 in the gerbil hippocampal CA1 region.
AB  - DNA methylation is a key epigenetic modification of DNA that is catalyzed by DNA
      methyltransferases (Dnmt). Increasing evidences suggest that DNA methylation in
      neurons regulates synaptic plasticity as well as neuronal network activity. In
      the present study, we investigated the changes in DNA methyltransferases 1
      (Dnmt1) immunoreactivity and its protein levels in the gerbil hippocampal CA1
      region after 5 min of transient global cerebral ischemia. CA1 pyramidal neurons
      were well stained with NeuN (a neuron-specific soluble nuclear antigen) antibody
      in the sham-group, Four days after ischemia-reperfusion (I-R), NeuN-positive
      ((+)) cells were significantly decreased in the stratum pyramidale (SP) of the
      CA1 region, and many Fluro-Jade B (a marker for neuronal degeneration)(+) cells
      were observed in the SP. Dnmt1 immunoreactivity was well detected in all the
      layers of the sham-group. Dnmt1 immunoreactivity was hardly detected only in the
      stratum pyramidale of the CA1 region from 4 days post-ischemia; however, at these
      times, Dnmt1 immunoreactivity was newly expressed in GABAergic interneurons or
      astrocytes in the ischemic CA1 region. In addition, the level of Dnmt1 was lowest
      at 4 days post-ischemia. In brief, both the Dnmt1 immunoreactivity and protein
      levels were distinctively decreased in the ischemic CA1 region 4 days after
      transient cerebral ischemia. These results indicate that the decrease of Dnmt1
      expression at 4 days post-ischemia may be related to ischemia-induced delayed
      neuronal death.

PMID- 22987059
TI  - Feasibility of noninvasive single-channel automated differentiation of
      obstructive and central hypopneas with nasal airflow.
AB  - BACKGROUND: The identification of obstructive and central hypopneas is considered
      challenging in clinical practice. Presently, obstructive and central hypopneas
      are usually not differentiated or scores lack reliability due to the technical
      limitations of standard polysomnography. Esophageal pressure measurement is the
      gold-standard for identifying these events but its invasiveness deters its usage
      in daily practice. OBJECTIVES: To determine the feasibility and efficacy of an
      automatic noninvasive analysis method for the differentiation of obstructive and
      central hypopneas based solely on a single-channel nasal airflow signal. The
      obtained results are compared with gold-standard esophageal pressure scores.
      METHODS: A total of 41 patients underwent full night polysomnography with
      systematic esophageal pressure recording. Two experts in sleep medicine
      independently differentiated hypopneas with the gold-standard esophageal pressure
      signal. Features were automatically extracted from the nasal airflow signal of
      each annotated hypopnea to train and test the automatic analysis method.
      Interscorer agreement between automatic and visual scorers was measured with
      Cohen's kappa statistic (K). RESULTS: A total of 1,237 hypopneas were visually
      differentiated. The automatic analysis achieved an interscorer agreement of K =
      0.37 and an accuracy of 69% for scorer A, K = 0.40 and 70% for scorer B and K =
      0.41 and 71% for the agreed scores of scorers A and B. CONCLUSIONS: The promising
      results obtained in this pilot study demonstrate the feasibility of noninvasive
      single-channel hypopnea differentiation. Further development of this method may
      help improving initial diagnosis with home screening devices and offering a means
      of therapy selection and/or control.

PMID- 22987060
TI  - Temporal changes in perihematomal apparent diffusion coefficient values during
      the transition from acute to subacute phases in patients with spontaneous
      intracerebral hemorrhage.
AB  - INTRODUCTION: Diffusion-weighted imaging (DWI) studies focusing on apparent
      diffusion coefficient (ADC) abnormalities have provided conflicting results about
      the nature and fate of perihematomal edema. METHODS: We investigated 35 patients
      with supratentorial spontaneous intracerebral hemorrhage (SICH) by using DWI
      scanning obtained at 48 h and 7 days after symptom onset. Regional ADC (rADC)
      values were measured in three manually outlined regions of interest: (1) the
      perihematomal hyperintense area, (2) 1 cm of normal appearing brain tissue
      surrounding the perilesional hyperintense rim, and (3) a mirror area, including
      the clot and the perihematomal region, located in the contralateral hemisphere.
      RESULTS: rADC mean levels were lower at 7 days than at 48 h in each ROI (p <
      0.00001), showing a progressive normalization of initial vasogenic values.
      Perihematomal vasogenic rADC values were more frequent (p < 0.00001) at 48 h than
      at 7 days, whereas perihematomal cytotoxic and normal rADC levels were more
      represented (p < 0.02 and p < 0.001, respectively) at 7 days than at 48 h. A
      neurological worsening was more frequent (p < 0.02) in patients with than in
      those without perihematomal cytotoxic rADC values at 7 days. CONCLUSION: Our
      findings suggest that the transition from acute to subacute phases after SICH is
      characterized by a progressive resolution of perihematomal vasogenic edema
      associated with an increase in cytotoxic ADC values. In the subset of patients
      with perihematomal cytotoxic rADC levels in subacute stage after bleeding,
      irreversible damage development seems to be related to poor clinical outcome.

PMID- 22987061
TI  - New and unconventional treatments for obstructive sleep apnea.
AB  - Although continuous positive airway pressure, oral appliances and surgical
      modifications of the airway are considered as part of the routine management of
      patients with obstructive sleep apnea, many new and unconventional therapies
      exist. Many of the trials using these new alternatives have been limited by
      insufficient data, poor trial design, small sample size, unclear inclusion
      criteria, lack of randomization, and lack of blinding, and on occasion are biased
      by retrospective design. Bariatric surgery, positional therapy, auto-titrating
      positive airway pressure, serotonin agents, wake promoting agents, genioglossus
      stimulation surgery, supplemental oxygen, nasal dilators, nasal expiratory
      resistor devices and oropharyngeal exercises will be reviewed. As obstructive
      sleep apnea impacts the individual and society at large, further research is
      needed to explore new therapeutic treatment options for obstructive sleep apnea.
      Therapeutic trials for obstructive sleep apnea must be of rigorous design to
      prove clinical effectiveness while taking into account both patient satisfaction
      and cost effectiveness.

PMID- 22987063
TI  - The effect of urban and rural habitats and resource type on activity budgets of
      commensal rhesus macaques (Macaca mulatta) in Bangladesh.
AB  - Macaques are characterized by their wide distribution and ability to adapt to a
      variety of habitats. Activity budgets are affected by habitat type, season, and
      food availability in relation to differing age-sex class and individual
      requirements. We conducted a comparative study on two commensal rhesus groups,
      one living in a rural village and the other in the center of urban Dhaka,
      Bangladesh. The study was conducted in three different seasons between 2007 and
      2009 in order to evaluate how habitat type and season affects their behavioral
      activities. Differences in food type and its availability between these two
      habitats were mainly responsible for the variations in activity budgets between
      groups. Feeding time in the rural group was significantly longer than that in the
      urban group. In contrast, grooming and object manipulation/play were
      significantly greater in the urban than the rural group. Seasonal variations in
      all major behaviors were significantly affected by group, with more time spent
      feeding in summer than in winter/dry season, and more time spent grooming and
      moving in winter/dry season than summer in the rural group. In contrast, time
      spent resting was greater in the monsoon and summer seasons than the winter/dry
      season in the urban group. Grooming time was greater in the winter/dry season
      than the monsoon and summer seasons. In both groups, immature of both sexes spent
      significantly more time on feeding and object manipulation/playing and less time
      resting than adults. Adult females spent more time grooming than males and
      immatures, of both sexes, in both groups. Moreover, the rural group spent most of
      their time feeding on garden/crop produce and wild plant food resources, while
      the urban group spent more time feeding on provisioned foods. These results
      showed that differences in the activity budgets of rural and urban dwelling
      macaques were due largely to the differences in available food resources.
      Commensal rhesus macaques show a high degree of behavioral flexibility in
      response to habitat and resource variability, and knowledge of these differences
      is important for the conservation and management of highly commensal primates.

PMID- 22987062
TI  - Healthful dietary patterns and type 2 diabetes mellitus risk among women with a
      history of gestational diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions.
      Women with gestational diabetes mellitus (GDM) are at high risk for T2DM after
      pregnancy. Adherence to healthful dietary patterns has been inversely associated
      with T2DM in the general population; however, whether these dietary patterns are
      associated with progression to T2DM among a susceptible population is unknown.
      METHODS: Four thousand four hundred thirteen participants from the Nurses' Health
      Study II cohort with prior GDM were followed up from 1991 to 2005. We derived the
      alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension
      (DASH), and alternate Healthy Eating Index (aHEI) dietary pattern adherence
      scores from a post-GDM validated food-frequency questionnaire, with cumulative
      average updating every 4 years. Multivariable Cox proportional hazards models
      estimated the relative risk (hazard ratios) and 95% confidence intervals.
      RESULTS: We observed 491 cases of incident T2DM during 52 743 person-years. All 3
      patterns were inversely associated with T2DM risk with adjustment for age, total
      calorie intake, age at first birth, parity, ethnicity, parental diabetes, oral
      contraceptive use, menopause, and smoking. When we compared participants with the
      highest adherence (quartile 4) vs lowest (quartile 1), the aMED pattern was
      associated with 40% lower risk of T2DM (hazard ratio, 0.60 [95% CI, 0.44-0.82;
      P=.002]); the DASH pattern, with 46% lower risk (0.54 [0.39-0.73; P.001]); and
      the aHEI pattern, with 57% lower risk (0.43 [0.31-0.59; P.001]). Adjustment for
      body mass index moderately attenuated these findings. CONCLUSIONS: Adherence to
      healthful dietary patterns is associated with lower T2DM risk among women with a
      history of GDM. The inverse associations are partly mediated by body mass index.

PMID- 22987064
TI  - Hunger strike among detainees: guidance for good medical practice.
AB  - Hunger strike is a regularly reported problem in prison. Although clinical
      situations are rarely severe, hospitalisation is often considered. In
      consequence, it is not only physicians working in prisons, but also hospital
      medical teams who face challenges related to hunger strike, involving somatic,
      psychological, legal and human rights aspects. Furthermore, deontological rules
      must be strictly respected when delivering care, particularly in prison setting.
      Starvation involves metabolic changes and can cause severe, and sometimes even
      irreversible or fatal complications. Moreover, the phase of re-alimentation
      should not be trivialised, as re-feeding syndrome is a potentially fatal
      phenomenon. This article provides guidance for monitoring and management of
      patients on hunger strike.

PMID- 22987065
TI  - [Absracts from the 40th Congress of the Deutschen Gesellschaft fur Rheumatologie
      (DGRh), September 19-22, 2012, Bochum, Germany].

PMID- 22987066
TI  - Strain screening, fermentation, separation, and encapsulation for production of
      nattokinase functional food.
AB  - This study presents a novel and integrated preparation technology for nattokinase
      functional food, including strain screening, fermentation, separation, and
      encapsulation. To rapidly screen a nattokinase-productive strain, PCR-based
      screening method was combined with fibrinolytic activity-based method, and a high
      productive strain, Bacillus subtilis LSSE-22, was isolated from Chinese soybean
      paste. Reduction of poly-gamma-glutamic acid (gamma-PGA) concentration may
      contribute to separation of nattokinase and reduction of late-onset anaphylaxis
      risk. Chickpeas were confirmed as the favorable substrate for enhancement of
      nattokinase production and reduction of gamma-PGA yield. Using cracked chickpeas,
      the nattokinase activity reached 356.25 +/- 17.18 FU/g (dry weight), which is
      much higher than previous reports. To further reduce gamma-PGA concentration,
      ethanol fractional extraction and precipitation were applied for separation of
      nattokinase. By extraction with 50 % and precipitation with 75 % ethanol
      solution, 4,000.58 +/- 192.98 FU/g of nattokinase powders were obtained, and the
      activity recovery reached 89 +/- 1 %, while gamma-PGA recovery was reduced to 21
      +/- 2 %. To improve the nattokinase stability at acidic pH condition, the
      nattokinase powders were encapsulated, and then coated with methacrylic acid
      ethyl acrylate copolymer. After encapsulation, the nattokinase was protected from
      being denatured under various acid conditions, and pH-responsible controlled
      release at simulated intestinal fluid was realized.

PMID- 22987067
TI  - Isolation and characterization of Pseudomonas sp. STM 997 from soil sample having
      potentiality to degrade 3,6-dimethyl-1-keto-1,2,3,4-tetrahydrocarbazole: a novel
      approach.
AB  - A pure colony of a bacterium from contaminated soil was isolated by exploiting
      3,6-dimethyl-1-keto-1,2,3,4-tetrahydrocarbazole, a novel carbazole derivative,
      having indole moiety as well as 3-methyl functionality both in aromatic and hydro
      aromatic moiety, as a sole source of carbon and energy. Taxonomical studies,
      biochemical analysis, and 16S rDNA sequence analysis indicated that the isolated
      strain has close similarity with Pseudomonas sp. Thin-layer chromatography
      followed by HPLC and mass spectroscopic study indicates that the isolated
      Pseudomonas sp. STM 997 degrades 3,6-dimethyl-1-keto-1,2,3,4-tetrahydrocarbazole,
      and this strain may be useful in the bioremediation of environments contaminated
      by the compounds containing carbazole moiety with methyl substituents at various
      reactive sites. This study also provides an evidence in favor of the suggested
      biodegradation of 3-methylcarbazole to carbazole in plants.

PMID- 22987068
TI  - An efficient antigene activity and antiproliferative effect by targeting the Bcl
      2 or survivin gene with triplex forming oligonucleotides containing a W-shaped
      nucleoside analogue (WNA-betaT).
AB  - Triplex forming oligonucleotides (TFOs) are some of the most promising tools in
      the antigene strategy for the development of gene targeting therapeutics.
      However, the stable triplex formation is restricted to the homopurine sequences
      consisting of purine nucleosides, dG and dA. Therefore, the T or dC nucleoside in
      the homopurine strand inhibits the stable triplex formation. We have developed W
      shaped nucleoside analogues (WNAs) for the formation of the unnatural type
      triplex DNA, with sequences containing the interrupting site in an antiparallel
      triplex formation. In the present study, we tested the antigene effect of TFOs
      having WNA-betaT, which increased the stability of the triplex formation with a
      target sequence including the TA interrupting site. We designed the GU TFO (WNA)
      and GU TFO (natural) for targeting sequences of the Bcl-2 or survivin oncogene.
      The gel shift assay showed that the TFO (WNA) formed more stable triplexes than
      the natural TFO. Remarkably, the Bcl-2- or survivin-targeted TFO (WNA) inhibited
      the cell proliferation and induced a caspase-dependent apoptosis. It was
      confirmed that the survivin-targeted TFO (WNA) more effectively decreased the
      number of survivin products in the A549 cell than the natural TFOs.

PMID- 22987069
TI  - The effect of ultrasound stimulation on the cytoskeletal organization of
      chondrocytes seeded in three-dimensional matrices.
AB  - The impact of low-intensity diffuse ultrasound (LIDUS) stimulation on the
      cytoskeletal organization of chondrocytes seeded in three-dimensional (3D)
      scaffolds was evaluated. Chondrocytes seeded on 3D chitosan matrices were exposed
      to LIDUS at 5.0 MHz (approx. 15 kPa, 51 s, 4 applications/day) in order to study
      the organization of actin, tubulin and vimentin. The results showed that actin
      presented a punctate cytosolic distribution and tubulin presented a quasiparallel
      organization of microtubules, whereas vimentin distribution was unaffected.
      Chondrocytes seeded on 3D scaffolds responded to US stimulation by the disruption
      of actin stress fibers and were sensitive to the presence of Rho-activated kinase
      (ROCK) inhibitor (Y27632). The gene expression of ROCK-I, a key element in the
      formation of stress fibers and mDia1, was significantly upregulated under the
      application of US. We conclude that the results of both the cytoskeletal analyses
      and gene expression support the argument that the presence of punctate actin upon
      US stimulation was accompanied by the upregulation of the RhoA/ROCK pathway.

PMID- 22987070
TI  - Characterization of human Spartan/C1orf124, an ubiquitin-PCNA interacting
      regulator of DNA damage tolerance.
AB  - Unrepaired DNA damage may arrest ongoing replication forks, potentially resulting
      in fork collapse, increased mutagenesis and genomic instability. Replication
      through DNA lesions depends on mono- and polyubiquitylation of proliferating cell
      nuclear antigen (PCNA), which enable translesion synthesis (TLS) and template
      switching, respectively. A proper replication fork rescue is ensured by the
      dynamic ubiquitylation and deubiquitylation of PCNA; however, as yet, little is
      known about its regulation. Here, we show that human Spartan/C1orf124 protein
      provides a higher cellular level of ubiquitylated-PCNA by which it regulates the
      choice of DNA damage tolerance pathways. We find that Spartan is recruited to
      sites of replication stress, a process that depends on its PCNA- and ubiquitin
      interacting domains and the RAD18 PCNA ubiquitin ligase. Preferential association
      of Spartan with ubiquitin-modified PCNA protects against PCNA deubiquitylation by
      ubiquitin-specific protease 1 and facilitates the access of a TLS polymerase to
      the replication fork. In concert, depletion of Spartan leads to increased
      sensitivity to DNA damaging agents and causes elevated levels of sister chromatid
      exchanges. We propose that Spartan promotes genomic stability by regulating the
      choice of rescue of stalled replication fork, whose mechanism includes its
      interaction with ubiquitin-conjugated PCNA and protection against PCNA
      deubiquitylation.

PMID- 22987071
TI  - p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6.
AB  - p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting
      G1 cell cycle arrest and cellular senescence. Consistent with this role, p21 is a
      downstream target of several tumour suppressors and oncogenes, and it is
      downregulated in the majority of tumours, including breast cancer. Here, we
      report that protein arginine methyltransferase 6 (PRMT6), a type I PRMT known to
      act as a transcriptional cofactor, directly represses the p21 promoter. PRMT6
      knock-down (KD) results in a p21 derepression in breast cancer cells, which is
      p53-independent, and leads to cell cycle arrest, cellular senescence and reduced
      growth in soft agar assays and in severe combined immunodeficiency (SCID) mice
      for all the cancer lines examined. We finally show that bypassing the p21
      mediated arrest rescues PRMT6 KD cells from senescence, and it restores their
      ability to grow on soft agar. We conclude that PRMT6 acts as an oncogene in
      breast cancer cells, promoting growth and preventing senescence, making it an
      attractive target for cancer therapy.

PMID- 22987072
TI  - Thromboprophylaxis and major oncologic surgery performed with epidural analgesia.
AB  - OBJECTIVE: To evaluate clinical outcomes in patients with cancer undergoing major
      abdominal surgery who received preoperative indwelling epidural catheters (ECs)
      and no postoperative thromboprophylaxis. DESIGN: Retrospective analysis of a
      prospective database. SETTING: Tertiary referral medical center. PATIENTS Between
      January 1, 2009, and July 31, 2011, 119 patients, with a mean age of 64.5 years
      (range, 34-95 years), underwent major abdominal oncologic surgery with an
      indwelling EC. MAIN OUTCOME MEASURES: Records of all patients were reviewed for
      age, duration of surgery, hospital length of stay, and clinical outcomes. All
      patients underwent lower extremity venous duplex ultrasonography prior to
      hospital discharge. RESULTS: The average operative time was 338 minutes. Mean
      (SD) intensive care unit stay was 2.8 (1.4) days (range, 1-7 days). Patients
      ambulated by postoperative day 1 or 2. Most ECs were removed on postoperative day
      4. There were no major complications from the EC. Fifty-two patients (44%) were
      treated with deep venous thrombosis prophylaxis on postoperative day 4 after
      removal of the EC. Lower extremity duplex studies showed 8 patients (6.7%) had an
      acute thrombus. One patient (0.8%) developed an asymptomatic proximal deep venous
      thrombosis and 7 patients (5.9%) developed distal superficial thrombi. No patient
      developed a pulmonary embolus. CONCLUSIONS Thromboembolic complications following
      major abdominal surgery for cancer may be reduced with the use of ECs. Epidural
      catheters may directly prevent deep venous thrombosis through sympathetic
      blockade, resulting in increased blood flow to the lower extremities. This effect
      may also be attributable to earlier ambulation. These results suggest that
      patients who have an EC and do not receive concurrent postoperative
      thromboprophylaxis do not have an increased risk for thromboembolic events.

PMID- 22987074
TI  - Renal dysfunction on admission, worsening renal function, and severity of acute
      kidney injury predict 2-year mortality in patients with acute myocardial
      infarction.
AB  - BACKGROUND: Recent studies have proven that initial renal dysfunction and
      worsening renal function during hospitalization can predict the clinical outcome
      of patients with acute myocardial infarction (AMI). There is limited study
      regarding acute kidney injury (AKI) by the RIFLE classification (Risk of renal
      failure, Injury to the kidney, Failure of kidney function, Loss of kidney
      function, and End-stage renal failure) to assess the outcome of AMI survivors.
      METHODS AND RESULTS: During a mean follow-up period of 635.3 +/- 204.9 days, the
      2-year mortality rate was 10.6% in 613 AMI patients who survived to discharge.
      Adjusted Cox regression analysis revealed that left ventricular dysfunction
      (<40%) [hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.11-7.20;
      P=0.029], estimated glomerular filtration rate <60 ml min(-1) x 1.73 m(-2) on
      admission (HR, 4.01; 95% CI, 1.51-10.62; P=0.005), and AKI severity by RIFLE
      classification during first week after hospitalization (Injury: HR, 8.11; 95% CI,
      2.53-26.05; P=0.001; Failure: HR, 19.28; 95% CI, 2.24-166.26; P=0.007) were
      independent predictors of 2-year mortality. CONCLUSIONS: Independent of initial
      renal dysfunction on admission, the AKI severity by RIFLE classification may be
      useful in establishing the hospital discharge risk score for predicting long-term
      mortality in AMI patients who survive to discharge.

PMID- 22987075
TI  - KCNE3 T4A as the genetic basis of Brugada-pattern electrocardiogram.
AB  - BACKGROUND: Brugada syndrome (BrS) is genetically heterogeneous. In Japanese BrS
      patients, except for SCN5A and KCNE5, mutations in the responsible genes have not
      yet been identified, and therefore the genetic heterogeneity remains poorly
      elucidated. METHODS AND RESULTS: Forty consecutive patients with Brugada-pattern
      electrocardiogram (ECG) underwent comprehensive genetic analysis of BrS-causing
      genes including SCN5A, SCN1B, SCN3B, CACNA1C, CACNB2, KCNE3 and KCNE5. Besides
      identifying 8 SCN5A mutations in the present cohort, a KCNE3 T4A mutation was
      found in a 55-year-old male patient who had experienced several episodes of
      syncope. A head-up tilt test during passive tilt provoked both hypotension and
      bradycardia, followed by syncope. He was therefore diagnosed with neurally
      mediated syncope (NMS). To characterize the functional consequence of the mutant,
      electrophysiological experiments using whole-cell patch-clamp methods and
      computer simulations using human right ventricular wall model were carried out.
      It was found that KCNE3 T4A increased I(to) recapitulated by heterologously
      coexpressing Kv4.3+KChIP2b+KCNE3-wild type or KCNE3-T4A in CHO cells.
      CONCLUSIONS: A KCNE3 T4A mutation was identified in a Japanese patient presenting
      Brugada-pattern ECG and NMS. Its functional consequence was the gain of function
      of I(to), which could underlie the pathogenesis of Brugada-pattern ECG. The data
      provide novel insights into the genetic basis of Japanese BrS.

PMID- 22987076
TI  - Anxiodepressive disorders and chronic psychological stress are associated with
      Tako-Tsubo cardiomyopathy- New Physiopathological Hypothesis.
AB  - BACKGROUND: Recent retrospective studies suggest that psychiatric disorders could
      be a predisposing risk factor for Tako-tsubo cardiomyopathy (TTC). The aim of the
      present study was to characterize the prevalence of anxiodepressive disorders
      (ADD) and chronic psychological stress (CPS) in patients with TTC or acute
      coronary syndrome (ACS). METHODS AND RESULTS: Between January 2010 and December
      2011, 45 consecutive patients with TTC were prospectively screened by systematic
      interview with the Mini International Neuropsychiatric Interview. CPS was
      systematically recorded. During the same period, 50 patients admitted for ACS
      with troponin elevation and matched for age and sex were prospectively included
      as a control group. An acute stressful event within 72 h before presentation was
      identified in 35 patients (78%) with TTC vs. 9 (18%) with ACS (P<0.001). Thirty
      five patients (78%) and 13 (26%) had ADD in the TTC and ACS groups, respectively
      (P<0.001). CPS was found in 20 patients (44%) and in 9 (18%) with TTC and ACS,
      respectively (P=0.005). CPS and/or ADD were found in 35 patients (78%) and in 18
      (36%) with TTC and ACS, respectively (P<0.001). CONCLUSIONS: ADD and CPS are
      common in patients with TTC and more frequent than in patients with ACS. This
      finding suggests that systemic effects of ADD and CPS could participate in the
      pathophysiology of TTC.

PMID- 22987077
TI  - Proof of efficacy is not enough: contemporary management of patients with
      metastatic renal cell carcinoma with targeted therapy.

PMID- 22987079
TI  - Clinically based palliative care training is needed urgently for all oncologists.

PMID- 22987078
TI  - Prognostic significance of the European LeukemiaNet standardized system for
      reporting cytogenetic and molecular alterations in adults with acute myeloid
      leukemia.
AB  - PURPOSE: To evaluate the prognostic significance of the international European
      LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid
      leukemia (AML). PATIENTS AND METHODS: We analyzed 1,550 adults with primary AML,
      treated on Cancer and Leukemia Group B first-line trials, who had pretreatment
      cytogenetics and, for cytogenetically normal patients, mutational status of NPM1,
      CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease
      free survival (DFS), and overall survival (OS) among patients classified into the
      four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse)
      separately for 818 younger (age < 60 years) and 732 older (age >= 60 years)
      patients. RESULTS: The percentages of younger versus older patients in the
      favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and
      adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had
      the best and the adverse group the worst CR rates, DFS, and OS in both age
      groups. Both intermediate groups had significantly worse outcomes than the
      favorable but better than the adverse group. Intermediate-I and intermediate-II
      groups in older patients had similar outcomes, whereas the intermediate-II group
      in younger patients had better OS but not better CR rates or DFS than the
      intermediate-I group. The prognostic significance of ELN classification was
      confirmed by multivariable analyses. For each ELN group, older patients had worse
      outcomes than younger patients. CONCLUSION: The ELN classification clearly
      separates the genetic groups by outcome, supporting its use for risk
      stratification in clinical trials. Because they have different proportions of
      genetic alterations and outcomes, younger and older patients should be reported
      separately when using the ELN classification.

PMID- 22987080
TI  - Oxaliplatin-induced thrombotic thrombocytopenic purpura: case report and
      literature review.

PMID- 22987081
TI  - Radiotherapy in older women with low-risk breast cancer: why has practice not
      changed?

PMID- 22987082
TI  - Reprise: gemtuzumab ozogamicin for older patients with acute myeloid leukemia.

PMID- 22987083
TI  - Randomized, open-label, phase III study comparing patupilone (EPO906) with
      pegylated liposomal doxorubicin in platinum-refractory or -resistant patients
      with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal
      cancer.
AB  - PURPOSE: This study compared the efficacy and safety of patupilone with those of
      pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or 
      resistant epithelial ovarian, primary fallopian tube, or primary peritoneal
      cancer. PATIENTS AND METHODS: Patients with three or fewer prior regimens were
      eligible if they had received first-line taxane/platinum-based combination
      chemotherapy and were platinum refractory or resistant. Patients were randomly
      assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD
      (50 mg/m(2) intravenously every 4 weeks). RESULTS: A total of 829 patients were
      randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically
      significant difference in overall survival (OS), the primary end point, between
      the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09),
      with median OS rates of 13.2 and 12.7 months, respectively. Median progression
      free survival was 3.7 months for both arms. The overall response rate (all
      partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v
      7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates
      were similar (59.5% v 56.3%, respectively). Frequently observed adverse events
      (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in
      the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%)
      in the PLD arm. CONCLUSION: Patupilone did not demonstrate significant
      improvement in OS compared with the active control, PLD. No new or unexpected
      serious AEs were identified.

PMID- 22987084
TI  - Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized
      trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP)
      with ACP plus trastuzumab as adjuvant therapy for patients with node-positive,
      human epidermal growth factor receptor 2-positive breast cancer.
AB  - PURPOSE: Cardiac dysfunction (CD) is a recognized risk associated with the
      addition of trastuzumab to adjuvant chemotherapy for human epidermal growth
      factor receptor 2-positive breast cancer, especially when the treatment regimen
      includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing
      assessment of cardiac safety and identification of risk factors for CD are
      important for optimal patient care. PATIENTS AND METHODS: In National Surgical
      Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830
      patients who met eligibility criteria for initiation of trastuzumab were
      evaluated for CD. Recovery from CD was also assessed. A statistical model was
      developed to estimate the risk of severe congestive heart failure (CHF). Baseline
      patient characteristics associated with anthracycline-related decline in cardiac
      function were also identified. RESULTS: At 7-year follow-up, 37 (4.0%) of 944
      patients who received trastuzumab experienced a cardiac event (CE) versus 10
      (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred
      in each arm of the protocol. A Cardiac Risk Score, calculated using patient age
      and baseline left ventricular ejection fraction (LVEF) by multiple-gated
      acquisition scan, statistically correlates with the risk of a CE. After stopping
      trastuzumab, the majority of patients who experienced CD recovered LVEF in the
      normal range, although some decline from baseline often persists. Only two CEs
      occurred more than 2 years after initiation of trastuzumab. CONCLUSION: The late
      development of CHF after the addition of trastuzumab to paclitaxel after
      doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit
      of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.

PMID- 22987085
TI  - Adverse prognostic impact of intratumor heterogeneous HER2 gene amplification in
      patients with esophageal adenocarcinoma.
AB  - PURPOSE: There is increasing recognition of the existence of intratumoral
      heterogeneity of the human epidermal growth factor receptor (HER2), which affects
      interpretation of HER2 positivity in clinical practice and may have implications
      for patient prognosis and treatment. We determined the frequency and prognostic
      impact of heterogeneous HER2 gene amplification and polysomy 17 in patients with
      esophageal adenocarcinoma (EAC). PATIENTS AND METHODS: HER2 amplification (by
      fluorescence in situ hybridization) was examined in surgical EAC specimens (n =
      675). HER2 heterogeneity was defined according to consensus guidelines as gene
      amplification (HER2/CEP17 ratio >= 2.0) in more than 5% but less than 50% of
      cancer cells. No patient received neoadjuvant or HER2-targeted therapy. Cox
      models were used to assess disease-specific survival (DSS) and overall survival
      (OS). RESULTS: Overall, 117 EACs (17%) demonstrated HER2 amplification, of which
      20 (17%) showed HER2 heterogeneity. All HER2-heterogeneous tumors were amplified.
      Among HER2-amplified tumors, heterogeneous tumors had significantly higher
      frequency of poor histologic grade and polysomy 17. In multivariable models that
      included number of metastatic lymph nodes, grade, tumor stage, and polysomy 17,
      only HER2 heterogeneity and node number were prognostic among HER2-amplified
      tumors, with heterogeneity showing worse DSS (hazard ratio, 2.04; 95% CI, 1.09 to
      3.79; P = .025) and OS (P = .026). Among HER2-nonamplified EACs, polysomy 17 was
      independently associated with worse DSS (P = .012) and OS (P = .023). CONCLUSION:
      Among HER2-amplified EACs, 17% show HER2 heterogeneity, which independently
      predicts for worse cancer-specific death. Among HER2-nonamplified EACs, polysomy
      17 is independently associated with worse survival. These novel findings
      demonstrate aggressive subgroups in HER2-amplified and -nonamplified EACs that
      have important implications for HER2 analysis and determination of benefit from
      HER2-targeted therapy.

PMID- 22987086
TI  - Guideline for the management of fever and neutropenia in children with cancer
      and/or undergoing hematopoietic stem-cell transplantation.
AB  - PURPOSE: To develop an evidence-based guideline for the empiric management of
      pediatric fever and neutropenia (FN). METHODS: The International Pediatric Fever
      and Neutropenia Guideline Panel is a multidisciplinary and multinational group
      composed of experts in pediatric oncology and infectious disease as well as a
      patient advocate. The Panel was convened for the purpose of creating this
      guideline. We followed previously validated procedures for creating evidence
      based guidelines. Working groups focused on initial presentation, ongoing
      management, and empiric antifungal therapy. Each working group developed key
      clinical questions, conducted systematic reviews of the published literature, and
      compiled evidence summaries. The Grades of Recommendation Assessment,
      Development, and Evaluation approach was used to generate summaries, and evidence
      was classified as high, moderate, low, or very low based on methodologic
      considerations. RESULTS: Recommendations were made related to initial
      presentation (risk stratification, initial evaluation, and treatment), ongoing
      management (modification and cessation of empiric antibiotics), and empiric
      antifungal treatment (risk stratification, evaluation, and treatment) of
      pediatric FN. For each recommendation, the strength of the recommendation and
      level of evidence are presented. CONCLUSION: This guideline represents an
      evidence-based approach to FN specific to children with cancer. Although some
      recommendations are similar to adult-based guidelines, there are key distinctions
      in multiple areas. Implementation will require adaptation to the local context.

PMID- 22987088
TI  - Long term follow-up of national surgical adjuvant breast and bowel project trial
      B-31: how well can we predict cardiac toxicity with trastuzumab?

PMID- 22987089
TI  - L-carnitine supplementation for the management of fatigue in patients with
      cancer: an eastern cooperative oncology group phase III, randomized, double
      blind, placebo-controlled trial.
AB  - PURPOSE: L-carnitine, a popular complementary and alternative medicine product,
      is used by patients with cancer for the treatment of fatigue, the most commonly
      reported symptom in this patient population. The purpose of this study was to
      determine the efficacy of L-carnitine supplementation as a treatment for fatigue
      in patients with cancer. PATIENTS AND METHODS: In this double-blind, placebo
      controlled trial, patients with invasive malignancies and fatigue were randomly
      assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo.
      The primary end point was the change in average daily fatigue from baseline to
      week 4 using the Brief Fatigue Inventory (BFI). RESULTS: Three hundred seventy
      six patients were randomly assigned to treatment with L-carnitine supplementation
      or placebo. L-carnitine supplementation resulted in significant carnitine plasma
      level increase by week 4. The primary outcome, fatigue, measured using the BFI,
      improved in both arms compared with baseline (L-carnitine: -0.96, 95% CI, -1.32
      to -0.60; placebo: -1.11, 95% CI -1.44 to -0.78). There were no statistically
      significant differences between arms (P = .57). Secondary outcomes, including
      fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue
      instrument, depression, and pain, did not show significant difference between
      arms. A separate analysis of patients who were carnitine-deficient at baseline
      did not show statistically significant improvement in fatigue or other outcomes
      after L-carnitine supplementation. CONCLUSION: Four weeks of 2 g of L-carnitine
      supplementation did not improve fatigue in patients with invasive malignancies
      and good performance status.

PMID- 22987087
TI  - Advances in immuno-positron emission tomography: antibodies for molecular imaging
      in oncology.
AB  - Identification of cancer cell-surface biomarkers and advances in antibody
      engineering have led to a sharp increase in the development of therapeutic
      antibodies. These same advances have led to a new generation of radiolabeled
      antibodies and antibody fragments that can be used as cancer-specific imaging
      agents, allowing quantitative imaging of cell-surface protein expression in vivo.
      Immuno-positron emission tomography (immunoPET) imaging with intact antibodies
      has shown success clinically in diagnosing and staging cancer. Engineered
      antibody fragments, such as diabodies, minibodies, and single-chain Fv (scFv) 
      Fc, have been successfully employed for immunoPET imaging of cancer cell-surface
      biomarkers in preclinical models and are poised to bring same-day imaging into
      clinical development. ImmunoPET can potentially provide a noninvasive approach
      for obtaining target-specific information useful for titrating doses for
      radioimmunotherapy, for patient risk stratification and selection of targeted
      therapies, for evaluating response to therapy, and for predicting adverse
      effects, thus contributing to the ongoing development of personalized cancer
      treatment.

PMID- 22987090
TI  - Choroidal schwannoma presenting as nonpigmented intraocular mass.

PMID- 22987091
TI  - Gemtuzumab ozogamicin: time to resurrect?

PMID- 22987092
TI  - Drug development for chronic cancers: time to think differently?

PMID- 22987093
TI  - The multidimensional nature of the financial and economic burden of a cancer
      diagnosis on patients and their families: qualitative findings from a country
      with a mixed public-private healthcare system.
AB  - PURPOSE: Although awareness is increasing that cancer can have an adverse
      financial and economic impact for patients, the overall burden remains poorly
      understood. To elucidate these issues, we used qualitative methods to explore the
      financial impact of a cancer diagnosis in Ireland, which has a mixed public
      private healthcare system and where sick leave and sick pay are at employers'
      discretion. METHODS: Face-to-face semi-structured interviews were conducted with
      hospital-based oncology social workers (OSWs; 21 OSWs from 11 hospitals) and
      patients (20 from eight hospitals; 11 breast, 5 prostate and 4 lung cancer).
      Participants were asked about the (1) extra expenses incurred, (2) cancer's
      impact on work and income, and (3) accessing financial assistance/social welfare
      benefits. The two interview sets were analysed separately using thematic
      analysis. RESULTS: Broad themes that emerged included the wide range of
      additional cancer-related medical and non-medical expenses incurred by all
      patients, including those with medical cards (which entitle the bearer to receive
      health services free of charge) and those with private health insurance; the
      major impact of cancer and its treatment on work and patient/household income
      (all patients who were working at diagnosis experienced a drop in income); and
      difficulties in accessing medical cards and benefits. CONCLUSIONS: This study
      reveals the complex, multidimensional nature of the financial and economic burden
      cancer imposes on patients and the whole family unit. Changes in income post
      cancer exacerbate the effects of cancer-related out-of-pocket expenses. These
      findings have implications for healthcare professionals, service providers and
      policy makers.

PMID- 22987095
TI  - Effectiveness of varenicline as an aid to smoking cessation in primary care: an
      observational study.
AB  - AIMS: Although varenicline is commonly prescribed in primary care, information on
      smoking-related comorbidities and the effectiveness of varenicline in this
      context in Germany is scarce. This study assessed the efficacy and safety of
      varenicline in a large sample of patients seeking smoking cessation treatment
      through their general practitioners. The frequency of comorbidities was also
      evaluated. METHODS: This was a 12-week, prospective, observational, non
      comparative phase IV trial conducted in Germany. Abstinence rates at week 12 were
      evaluated by verbal reporting using the nicotine use inventory. RESULTS: Overall,
      1,391 subjects were enrolled; 1,177 received study medication and were evaluated
      for effectiveness and safety. At the end of the study, 71.1% (95% confidence
      interval 68.5-73.7) of subjects were abstinent. There were a total of 205 all
      causality adverse events; 2.2% were classified as serious or severe. There were
      no fatal adverse events. At inclusion, 66.7% of participants had at least 1
      concurrent comorbidity, with chronic obstructive pulmonary disease (35.5%),
      hypertension (29.6%) and depression (10.4%) being the most commonly reported.
      CONCLUSION: These real-world data indicate that varenicline is an effective and
      well-tolerated smoking cessation treatment when used in the primary care setting
      including patients with smoking-related comorbidities.

PMID- 22987096
TI  - Chiral Ag(I) and Pt(II) complexes of ditopic NHC ligands: synthesis, structural
      and spectroscopic properties.
AB  - The butyl and isopropyl derivatives (4I, 5Br) of chiral pool derived bis
      imidazolium dehydrohexitol salts have been prepared. The ditopic N-heterocyclic
      carbenes 4 and 5 form dinuclear Ag(I) and Pt(II) complexes. All compounds were
      fully characterised by multinuclear NMR spectroscopy. The bis-imidazolium salt 4I
      and platinum complexes cis-[Pt(2)(MU-2)(dmso)(2)Cl(4)] and cis-[Pt(2)(MU
      4)(dmso)(2)Cl(4)] were characterised by X-ray crystallography. In the case of the
      Pt(II) complexes, the carbene ring is positioned in a sterically preferred
      orientation, approximately perpendicular to the platinum coordination plane. The
      (1)H, (13)C, (15)N and (195)Pt NMR spectra of the platinum complexes show the
      presence of rotamers due to hindered rotation about the carbene-metal bond.

PMID- 22987094
TI  - Systematic review of cytokines and growth factors for the management of oral
      mucositis in cancer patients.
AB  - PURPOSE: The aim of this project was to review the literature and define clinical
      practice guidelines for the use of cytokines and growth factor agents for the
      prevention or treatment of oral mucositis induced by cancer chemotherapy or
      radiotherapy. METHODS: A systematic review was conducted by the Mucositis Study
      Group of the Multinational Association of Supportive Care in Cancer/International
      Society for Oral Oncology (MASCC/ISOO). The body of evidence for each
      intervention, in each cancer treatment setting, was assigned an evidence level.
      Based on the evidence level, one of the following three guideline determinations
      was possible: Recommendation, Suggestion, No guideline possible. RESULTS: Sixty
      four clinical studies across 11 interventions were evaluated. A recommendation
      was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60
      MUg/kg per day for 3 days prior to conditioning treatment and for 3 days post
      transplant for prevention of oral mucositis in patients receiving high-dose
      chemotherapy and total body irradiation followed by autologous stem cell
      transplantation for hematological malignancies. A suggestion was made against
      using granulocyte macrophage colony-stimulating factor mouthwash for the
      prevention of oral mucositis in the setting of high-dose chemotherapy followed by
      autologous or allogeneic stem cell transplantation. No guideline was possible for
      any other cytokine or growth factor agents due to inconclusive evidence.
      CONCLUSIONS: Of the cytokine and growth factor agents studied for oral mucositis,
      the evidence only supports use of palifermin in the specific population listed
      above. Additional well-designed research is needed on other cytokine and growth
      factor interventions and in other cancer treatment settings.

PMID- 22987097
TI  - The effect of intraoperative rectal washout on local recurrence after rectal
      cancer surgery: a meta-analysis.
AB  - BACKGROUND: Implantation of exfoliated cancer cells has been suggested as a
      possible mechanism of local recurrence at the site of colorectal anastomosis.
      Intraoperative rectal washout has been suggested to eliminate free cancer cells;
      however, there is no conclusive evidence of a beneficial effect of intraoperative
      rectal washout on local recurrence after anterior resection of rectal cancer.
      METHODS: Studies published through February 2012 evaluating the impact of
      intraoperative rectal washout for local recurrence or positive cytology from
      donuts wash were identified by an electronic literature search. A meta-analysis
      was performed using the DerSimonian-Laird random-effects models to compute risk
      ratio (RR) along with 95% confidence intervals (CI). RESULTS: Nine studies met
      the inclusion criteria, yielding a total of 5,395 patients. Eight studies
      evaluated overall local recurrence, including anastomotic recurrence, and five of
      the eight studies evaluated anastomotic recurrence separately. Two studies
      evaluated positive cytology from donuts wash. Local recurrence rate was 5.79% in
      the washout group and 10.05% in the no washout group-a difference that was
      statistically significant (RR = 0.57; 95% CI = 0.46-0.71; P < 0.00001). Rectal
      washout significantly reduced the risk of anastomotic recurrence (RR = 0.3; 95%
      CI = 0.12-0.71; P = 0.007). No influence of rectal washout was observed on
      positive cytology from donuts wash. CONCLUSIONS: From the results of this meta
      analysis, it may be justified to recommend intraoperative rectal washout to
      prevent local recurrence in rectal cancer surgery.

PMID- 22987098
TI  - Influence of comorbidity and age on 1-, 2-, and 3-month postoperative mortality
      rates in gastrointestinal cancer patients.
AB  - BACKGROUND: Studies on the impact of comorbidity and age on postoperative outcome
      after gastrointestinal tumor resection are scarce. In this study we investigated
      the impact of comorbidity and age on 30-, 60-, and 90-day mortality after
      resection of esophageal, gastric, periampullary, colon, and rectal cancer.
      METHODS: The study included 8,583 patients recorded in the population-based
      Netherlands Cancer Registry, regions Eindhoven (Eindhoven Cancer Registry) and
      Mid and South Limburg, who underwent resection for cancer stage I-III. Patients
      were diagnosed between 2005 and 2010. Age was categorized as <65, 65-74, and >=75
      years. RESULTS: Comorbidity was present in more than two-thirds (n = 5,910) of
      patients. The 30-day mortality rates ranged from 0.5 % for rectal cancer patients
      <65 years to 12.8 % for gastric cancer patients >=75 years. Patients with
      comorbidity who underwent esophageal tumor resection had the highest mortality
      rates, ranging from 8.4 % for 30-day to 12.0 % for 90-day mortality, while rectal
      cancer patients had the lowest rates, that is, 4.3-6.4 %, respectively. In
      multivariable analyses, cardiac disease (odds ratio [OR] = 1.74, 95 % confidence
      interval [95 % CI] = 1.32-2.30), vascular disease (OR = 1.41, 95 % CI = 1.02
      1.95) and previous malignancies (OR = 1.38, 95 % CI = 1.02-1.86) in colon cancer,
      and cardiac disease (OR = 1.81, 95 % CI = 1.10-2.98) and vascular disease (OR =
      1.95, 95 % CI = 1.11-3.42) in rectal cancer were associated with the highest 30
      day mortality. CONCLUSIONS: Postoperative mortality extends beyond 30 days.
      Comorbidity and older age are associated with early postoperative mortality after
      gastrointestinal cancer resection. Underlying comorbidity should be identified
      preoperatively with attention to patients' specific needs to optimally attenuate
      risk prior to surgery. A less aggressive treatment approach may well be
      considered in these groups.

PMID- 22987099
TI  - Breast cancer: Chemo fog becomes clearer.

PMID- 22987104
TI  - Genetics: Finding the path to everolimus sensitivity.

PMID- 22987105
TI  - Multi-parameter measurement of the permeability transition pore opening in
      isolated mouse heart mitochondria.
AB  - The mitochondrial permeability transition pore (mtPTP) is a non specific channel
      that forms in the inner mitochondrial membrane to transport solutes with a
      molecular mass smaller than 1.5 kDa. Although the definitive molecular identity
      of the pore is still under debate, proteins such as cyclophilin D, VDAC and ANT
      contribute to mtPTP formation. While the involvement of mtPTP opening in cell
      death is well established(1), accumulating evidence indicates that the mtPTP
      serves a physiologic role during mitochondrial Ca(2+) homeostasis(2),
      bioenergetics and redox signaling( 3). mtPTP opening is triggered by matrix
      Ca(2+) but its activity can be modulated by several other factors such as
      oxidative stress, adenine nucleotide depletion, high concentrations of Pi,
      mitochondrial membrane depolarization or uncoupling, and long chain fatty
      acids(4). In vitro, mtPTP opening can be achieved by increasing Ca(2+)
      concentration inside the mitochondrial matrix through exogenous additions of
      Ca(2+) (calcium retention capacity). When Ca(2+) levels inside mitochondria reach
      a certain threshold, the mtPTP opens and facilitates Ca(2+) release, dissipation
      of the proton motive force, membrane potential collapse and an increase in
      mitochondrial matrix volume (swelling) that ultimately leads to the rupture of
      the outer mitochondrial membrane and irreversible loss of organelle function.
      Here we describe a fluorometric assay that allows for a comprehensive
      characterization of mtPTP opening in isolated mouse heart mitochondria. The assay
      involves the simultaneous measurement of 3 mitochondrial parameters that are
      altered when mtPTP opening occurs: mitochondrial Ca(2+) handling (uptake and
      release, as measured by Ca(2+) concentration in the assay medium), mitochondrial
      membrane potential, and mitochondrial volume. The dyes employed for Ca(2+)
      measurement in the assay medium and mitochondrial membrane potential are Fura FF,
      a membrane impermeant, ratiometric indicator which undergoes a shift in the
      excitation wavelength in the presence of Ca(2+), and JC-1, a cationic,
      ratiometric indicator which forms green monomers or red aggregates at low and
      high membrane potential, respectively. Changes in mitochondrial volume are
      measured by recording light scattering by the mitochondrial suspension. Since
      high-quality, functional mitochondria are required for the mtPTP opening assay,
      we also describe the steps necessary to obtain intact, highly coupled and
      functional isolated heart mitochondria.

PMID- 22987106
TI  - Junctional ectopic tachycardia after congenital heart surgery in the current
      surgical era.
AB  - To determine the incidence of postoperative junctional ectopic tachycardia (JET)
      in a modern cohort of pediatric patients, evaluate possible risk factors for JET,
      and examine the effects of JET on postoperative morbidity and mortality. JET is
      common after congenital heart surgery. JET-related mortality has been a rare
      event at our center, which is different from previous reports. We reviewed
      records for pediatric patients who had postoperative arrhythmias between January
      2006 and June 2010 at a large tertiary-care children's hospital. We performed a
      matched case-control study to identify risk factors for JET and a matched-cohort
      study to compare outcomes between patients and controls. Whenever possible, each
      JET case was randomly matched to two controls on the basis of lesion, repair, and
      surgical period. We identified 54 patients with JET (incidence = 1.4 %). After
      multivariate logistic regression analysis, low operative weight, cardiopulmonary
      bypass (CPB) duration >100 min, and immediate postoperative serum lactic acid
      level >20 mg/dl were associated with increased odds of developing JET. Patients
      with JET had longer mechanical ventilation time, cardiac intensive care unit
      (CICU) stay, and hospital stay. There was only one death in JET group (1.8 %)
      with no significant difference compared with the control group. JET remains a
      relatively common postoperative arrhythmia, but it is less frequent than
      previously reported. JET occurs more commonly in smaller patients with longer CPB
      runs and significant postoperative lactic acidosis levels. Mortality associated
      with JET is lower than historically reported, but morbidity remains high.

PMID- 22987107
TI  - Prediction of residual valvular lesions in rheumatic heart disease: role of
      adhesion molecules.
AB  - Rheumatic heart disease (RHD) is a chronic condition characterized by fibrosis
      and scarring of the cardiac valves and damage to the heart muscle, leading to
      congestive heart failure and death. This prospective cohort study was conducted
      to investigate the possible relation between the levels of serum adhesion
      molecules and acute rheumatic fever (ARF) carditis, valvular insult severity, and
      residual valvular lesion after improvement of rheumatic activity. Serum levels of
      intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and E-selectin were assayed by enzyme-linked immunoassay (ELISA) for 50
      children with ARF carditis during activity and after improvement and for 50
      healthy children as control subjects. After the acute attack, patients were
      followed up regularly to detect residual valvular lesion. The serum levels of
      these adhesion molecules were significantly higher in the patients than in the
      control group (p < 0.001). In addition, the levels of serum adhesion molecules
      were significantly higher in the patients with severe carditis than in the
      patients with mild to moderate carditis (p < 0.001). Among the severe carditis
      group, the level of serum adhesion molecules was significantly higher among the
      patients with heart failure than among the patients without heart failure (p <
      0.001). Furthermore, the pretreatment serum levels of ICAM-1 and VCAM-1 were
      significantly higher among the patients with residual valve lesion (p = 0.002)
      than among those without the lesion (p < 0.001). The cutoff values were obtained
      for the prediction of residual valvular lesion (ICAM-1, >1,032.3 MUg/ml; VCAM-1,
      >3,662.3 MUg/ml; E-selectin, >104.8 MUg/ml). Finally, by combining the three
      adhesion molecules in a single prediction model, the highest area under the curve
      (AUC) +/- standard error (SE) was obtained (0.869 +/- 0.052), and the positive
      likelihood ratio for having a residual valvular lesion was increased (17.33).
      Levels of serum adhesion molecules could predict residual valvular lesions in RHD
      patients. The authors recommend that the serum level of adhesion molecules be
      measured in all cases of ARF carditis.

PMID- 22987108
TI  - Fetal long QT syndrome manifested as atrioventricular block and ventricular
      tachycardia: a case report and a review of the literature.
AB  - Fetal onset of congenital long QT syndrome (LQTS) is a rare manifestation, and
      prenatal diagnosis is difficult. This report describes a boy who presented with
      both atrioventricular (AV) block and ventricular tachycardia during the antenatal
      period. The early postnatal electrocardiogram showed prolongation of the QT
      interval and AV block, subsequently leading to a polymorphic ventricular
      tachycardia torsade de pointes. This unique feature of congenital LQTS has a poor
      outcome, but the boy was successfully treated with beta-blockers and implantation
      of an automated cardioverter-defibrillator. The intrauterine manifestation of
      fetal AV block and ventricular tachycardia should raise a high suspicion of
      congenital LQTS, and the strong association with a malignant clinical course
      should warrant special evaluation. The literature on the prenatal diagnosis,
      fetal therapy, and neonatal outcome of this condition also are reviewed.

PMID- 22987109
TI  - Transcatheter closure of multiple perimembranous ventricular septal defects with
      septal aneurysm using two overlapping Amplatzer Duct Occluders II.
AB  - Ventricular septal defect (VSD) is a common congenital heart defect in children.
      Perimembranous VSD (Pm VSD), a defect involving the membranous septum and the
      adjacent portion of the muscular septum, accounts for about 70 % of cases.
      Transcatheter closure of Pm VSDs using the Amplatzer Pm VSD device, although
      successful in many patients, has been associated with major adverse events.
      Complete heart block, thromboembolism, and new-onset valvular regurgitations in
      patients undergoing VSD closure using the Pm VSD occluder have been reported [3].
      Recently, a new retrograde approach for transcatheter closure of Pm VSDs using
      the Amplatzer Duct Occluder II (ADO II) has been described with a 90 % success
      rate [1]. This report describes a child who had multiple Pm VSDs with septal
      aneurysm undergoing successful transcatheter closure using two ADO II occluders
      with relative ease.

PMID- 22987110
TI  - Pulmonary hypertension in Kawasaki disease.
AB  - This report describes the case of two pediatric patients who demonstrated
      echocardiographic evidence of pulmonary hypertension (PH) during the acute phase
      of Kawasaki disease. The etiology of PH development in this setting is currently
      unknown, but the authors hypothesize that pulmonary vasculitis may play a
      significant role. Fortunately, the PH appeared to be self-limited and resolved in
      both cases with routine treatment of Kawasaki disease.

PMID- 22987111
TI  - Chest pain in the emergency department: the case against our current practice of
      routine noninvasive testing.
AB  - Current clinical practice for patients presenting to the emergency department
      with a resolved episode of chest pain and no electrographic or biomarker
      abnormalities is to conduct routine noninvasive testing, in accordance with
      American College of Cardiology and American Heart Association guidelines. The
      rationale is to further reduce the risk of missing a myocardial infarction, a
      major source of suits filed against emergency department physicians. Patients
      with negative stress test results may be reassured, with low event rates in the
      subsequent 30 days. Patients with positive stress test results have higher 30-day
      event rates, and a small fraction undergo revascularization procedures. Despite
      this endorsement, open questions remain. Does our current practice lead to the
      stenting of asymptomatic patients in the inevitable cases where the inciting pain
      was noncardiac? And, most importantly, does our practice improve outcomes?
      Randomized trials evaluating routine stress testing in other contexts have
      yielded negative results, despite diagnosing significant coronary artery disease.
      Population data suggest that our current practice may be increasing the diagnosis
      of coronary artery disease and the rate of intervention while failing to decrease
      rates of myocardial infarction. We propose that randomized trials be conducted to
      evaluate whether any testing is better than no further intervention. Data from
      such an evidence-based approach has the potential to reverse our current
      practice.

PMID- 22987113
TI  - Ten years of neuroinformatics.

PMID- 22987112
TI  - Slow spontaneous alpha-to-beta structural conversion in a non-denaturing neutral
      condition reveals the intrinsically disordered property of the disulfide-reduced
      recombinant mouse prion protein.
AB  - In prion diseases, the normal prion protein is transformed by an unknown
      mechanism from a mainly alpha-helical structure to a beta-sheet-rich, disease
      related isomer. In this study, we surprisingly found that a slow, spontaneous
      alpha-to-coil-to-beta transition could be monitored by circular dichroism
      spectroscopy in one full-length mouse recombinant prion mutant protein, denoted
      S132C/N181C, in which the endogenous cysteines C179 and C214 were replaced by Ala
      and S132 and N181 were replaced by Cys, during incubation in a non-denaturing
      neutral buffer. No denaturant was required to destabilize the native state for
      the conversion. The product after this structural conversion is toxic beta
      oligomers with high fluorescence intensity when binding with thioflavin T. Site
      directed spin-labeling ESR data suggested that the structural conversion involves
      the unfolding of helix 2. After examining more protein mutants, it was found that
      the spontaneous structural conversion is due to the disulfide-deletion (C to A
      mutations). The recombinant wild-type mouse prion protein could also be
      transformed into beta-oligomers and amyloid fibrils simply by dissolving and
      incubating the protein in 0.5 mM NaOAc (pH 7) and 1 mM DTT at 25 degrees C with
      no need of adding any denaturant to destabilize the prion protein. Our findings
      indicate the important role of disulfide bond reduction on the structural
      conversion of the recombinant prion protein, and highlight the special
      "intrinsically disordered" conformational character of the recombinant prion
      protein.

PMID- 22987114
TI  - Global alteration of microRNAs and transposon-derived small RNAs in cotton
      (Gossypium hirsutum) during Cotton leafroll dwarf polerovirus (CLRDV) infection.
AB  - Small RNAs (sRNAs) are a class of non-coding RNAs ranging from 20- to 40
      nucleotides (nts) that are present in most eukaryotic organisms. In plants, sRNAs
      are involved in the regulation of development, the maintenance of genome
      stability and the antiviral response. Viruses, however, can interfere with and
      exploit the silencing-based regulatory networks, causing the deregulation of
      sRNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). To
      understand the impact of viral infection on the plant sRNA pathway, we deep
      sequenced the sRNAs in cotton leaves infected with Cotton leafroll dwarf virus
      (CLRDV), which is a member of the economically important virus family
      Luteoviridae. A total of 60 putative conserved cotton miRNAs were identified,
      including 19 new miRNA families that had not been previously described in cotton.
      Some of these miRNAs were clearly misregulated during viral infection, and their
      possible role in symptom development and disease progression is discussed.
      Furthermore, we found that the 24-nt heterochromatin-associated siRNAs were
      quantitatively and qualitatively altered in the infected plant, leading to the
      reactivation of at least one cotton transposable element. This is the first study
      to explore the global alterations of sRNAs in virus-infected cotton plants. Our
      results indicate that some CLRDV-induced symptoms may be correlated with the
      deregulation of miRNA and/or epigenetic networks.

PMID- 22987116
TI  - Single cell molecular recognition of migrating and invading tumor cells using a
      targeted fluorescent probe to receptor PTPmu.
AB  - Detection of an extracellular cleaved fragment of a cell-cell adhesion molecule
      represents a new paradigm in molecular recognition and imaging of tumors. We
      previously demonstrated that probes that recognize the cleaved extracellular
      domain of receptor protein tyrosine phosphatase mu (PTPmu) label human
      glioblastoma brain tumor sections and the main tumor mass of intracranial
      xenograft gliomas. In this article, we examine whether one of these probes, SBK2,
      can label dispersed glioma cells that are no longer connected to the main tumor
      mass. Live mice with highly dispersive glioma tumors were injected intravenously
      with the fluorescent PTPmu probe to test the ability of the probe to label the
      dispersive glioma cells in vivo. Analysis was performed using a unique three
      dimensional (3D) cryo-imaging technique to reveal highly migratory and invasive
      glioma cell dispersal within the brain and the extent of colabeling by the PTPmu
      probe. The PTPmu probe labeled the main tumor site and dispersed cells up to 3.5
      mm away. The cryo-images of tumors labeled with the PTPmu probe provide a novel,
      high-resolution view of molecular tumor recognition, with excellent 3D detail
      regarding the pathways of tumor cell migration. Our data demonstrate that the
      PTPmu probe recognizes distant tumor cells even in parts of the brain where the
      blood-brain barrier is likely intact. The PTPmu probe has potential translational
      significance for recognizing tumor cells to facilitate molecular imaging, a more
      complete tumor resection and to serve as a molecular targeting agent to deliver
      chemotherapeutics to the main tumor mass and distant dispersive tumor cells.

PMID- 22987115
TI  - Transcriptomic changes and signalling pathways induced by arsenic stress in rice
      roots.
AB  - Arsenic (As) is considered the most common toxic metalloid, but its molecular
      mode of action is not well understood. We investigated whether arsenate [As(V)]
      can induce intracellular reactive oxygen species production and calcium
      oscillation in rice roots. To better understand the molecular basis of plant cell
      responses to As, we performed a large-scale analysis of the rice transcriptome
      during As(V) stress. As(V) induced genes involved in abiotic stress,
      detoxification pathways and secondary metabolic process. Genes involved in
      secondary cell wall biogenesis, cell cycle and oligopeptide transport were mainly
      downregulated. Genes encoding signalling components such as receptor-like
      cytoplasmic kinases protein kinase, APETALA2/ethylene response factor, heat shock
      factor, MYB and zinc-finger protein expressed in inflorescence meristem
      transcription factors were increased in expression. The expression of GARP-G2
      like and C3H transcription factors was specifically modulated by As(V) stress.
      The predominant families of As(V)-regulated transporters belonged to the ATP
      binding cassette superfamily and telurite-resistance/dicarboxylate transporters.
      Several factors involved in signaling, such as mitogen-activated protein kinase
      (MAPK), MAPK kinase kinase and calcium-dependent protein kinase (CDPK), were also
      upregulated. Moreover, As(V) markedly increased the activity of MAPKs and CDPK
      like kinases, and CDPK and NADPH oxidases were involved in As-induced MAPK
      activation. Further characterization of these As(V)-responsive genes and
      signalling pathways may help better understand the mechanisms of metalloid
      uptake, tolerance and detoxification in plants.

PMID- 22987118
TI  - Decreases in diameters of treated abdominal aortic aneurysms and reduction in
      rupture rate.
AB  - OBJECTIVE: To determine whether the diameters of treated abdominal aortic
      aneurysms (AAAs) have changed during the last 10 years. DESIGN, SETTING, AND
      PATIENTS: A retrospective record review was completed on all patients undergoing
      any AAA repair from January 1, 2000, through December 31, 2009, at a single high
      volume institution. All cases of repaired AAAs that had computed tomographic
      scans within 3 months of surgery were included. The mean and median maximal
      diameters of AAAs were noted. Correlation and regression analyses were used. MAIN
      OUTCOME MEASURES: The mean and median maximal diameters of AAAs. RESULTS: Of 360
      patients with treated AAAs, 339 met the inclusion criteria. The mean (SD)
      diameter of repaired AAAs decreased from 6.49 (1.46) cm (median, 6.40 cm) in 2000
      to 5.83 (1.23) cm (median, 5.60 cm) in 2009. Correlation analysis confirmed a
      decrease in diameter across years (Pearson R = -0.141; P = .01). A fitted
      regression line also showed a decreasing trend (slope = -0.059 cm per year; P =
      .01). CONCLUSIONS: The diameters of repaired AAAs at our hospital have decreased
      progressively during the last decade. This observation is consistent with a
      reduction in the expansion rates of AAAs and may account for the progressive
      decreases in the aneurysm rupture rate in the United States.

PMID- 22987117
TI  - CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors:
      clinical correlations in a single-centre patient cohort.
AB  - OBJECTIVE: To determine if molecular and immunohistochemical (IHC) features of
      the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history
      of parathyroid malignancy, particularly atypical adenoma, as seen in a single
      centre patient cohort. METHODS: Matched tumor and non-tumor tissues were obtained
      from 46 patients with parathyroid carcinoma (CA) (n = 15), atypical adenoma (AA)
      (n = 14) and typical adenoma (TA) (n = 17), as defined by standardized
      histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene
      were sequenced to identify germline or somatic mutations. IHC staining for
      parafibromin was performed and scored as positive if nuclear staining was at
      least partially IHC-positive. RESULTS: Mutations of CDC73 were observed in 9/15
      (60 %) CA, 2/14 (14 %) AA, and 1/17 (6 %) TA tumors. A recurrent two basepair
      mutation in exon 7 -- c.679_680delAG -- accounted for half of all identified
      mutations. Absence of parafibromin nuclear staining was noted in 8/12 (67 %) CA,
      2/13 (15 %) AA, and 3/17 (18 %) TA tumors. Median follow up times were 88 months
      for CA, 76 months for AA, and 104 months for TA patients. One patient, a member
      of a previously reported multiplex family with a germline CDC73 mutation was
      found to have a second adenoma after removal of an atypical adenoma. CONCLUSIONS:
      Molecular screening and IHC are both useful tools in the differential diagnosis
      of parathyroid tumors, but both have limited sensitivity and specificity. CDC73
      mutations and negative immunostaining were common in atypical adenomas, but no
      local recurrence was observed in any case with successful surgical removal after
      follow-up periods of 27 to 210 months.

PMID- 22987120
TI  - Medical management of radiation accidents: capabilities and deployment principles
      of the Bundeswehr Institute of Radiobiology.
AB  - Radiation accidents are fortunately infrequent occurrences, but since their
      consequences can be very serious as in the Chernobyl and the Fukushima nuclear
      accidents, medical management of radiation accidents is of great importance.
      Besides several other tasks, medical management of radiation accidents is one of
      the key tasks of the Bundeswehr Institute of Radiobiology. Within a Task Force
      Unit for medical chemical, biological, radiological, and nuclear (CBRN) Defense,
      the institute provides designated personnel who will perform clinical
      investigations on the scene and will liaise with the institute, where different
      methods for biological dosimetry and dose reconstruction will be performed. The
      most important aspects of efficient medical management of radiation accidents are
      diagnosis of radiation-induced health damage, determination of the cause, dealing
      with contamination/incorporation, pathophysiological and therapeutic principles,
      preparatory planning, national and international cooperation and training.
      Military and non-military institutions have to work closely together when it
      comes to radiation accidents and since national resources are limited and could
      be exhausted, international networks can help to ensure medical treatment for
      radiation accident victims.

PMID- 22987119
TI  - Evaluation of personal dose equivalent using optically stimulated luminescent
      dosemeters in Marumori after the Fukushima nuclear accident.
AB  - The personal dose equivalent for 36 Marumori residents living in wooden houses
      was evaluated using optically stimulated luminescent dosemeters after the
      Fukushima nuclear accident. The cumulative doses to residents over 200 d from 1
      September 2011 ranged from 536 to 1490 uSv. In each resident's house, the indoor
      and outdoor ambient dose equivalents were measured with an NaI scintillation
      survey meter. A linear relationship with a slope of 0.5 was found between them;
      however, the ratio of the indoor to the outdoor ambient dose equivalent varied
      from 0.36 to 1.0. A better linear relationship was observed between the personal
      dose equivalent and the indoor ambient dose equivalent compared with that between
      the personal dose equivalent and the outdoor ambient dose equivalent. These
      results indicate that the individual exposure dose depends on the indoor ambient
      dose equivalent rather than the outdoor ambient dose equivalent. These results
      should be very helpful in obtaining the countermeasures to reduce residents'
      exposure dose.

PMID- 22987121
TI  - Highlights and pitfalls of 20 years of application of computerised glow curve
      analysis to thermoluminescence research and dosimetry.
AB  - The technical and dosimetric aspects of computerised glow curve analysis are
      described in detail including a review of the current 'state-of-the-achieved' in
      applications to environmental and personal dosimetry, clinical dosimetry, quality
      control, characterisation of new materials, continuing characterisation of 'old'
      materials, heavy charged particle dosimetry, mixed field n-gamma dosimetry, X-ray
      dosimetry and other aspects of thermoluminescence dosimetry. Fearless emphasis is
      placed on 'pitfalls' as well as successes.

PMID- 22987122
TI  - Metal-free reactions of alkynes via electrophilic iodocarbocyclizations.
AB  - Despite attracting tremendous interest over the last few decades, the field of
      electrophilic cyclizations is still continuously and rapidly developing.
      Particularly, metal-free reactions that involve the activation of an alkyne using
      electrophilic halogen sources are powerful tools in the repertoire of synthetic
      chemists. This brief overview highlights recent progress in C-C bond-forming
      halocyclizations allowing for the reaction of alkynes with carbon-nucleophiles.
      Primarily guided by the type of carbon nucleophile, methods are categorized as
      the addition of arene, malonate, and olefin nucleophiles.

PMID- 22987123
TI  - Legal liability and the uncertain nature of risk prediction: the case of breast
      cancer risk prediction models.
AB  - BACKGROUND: The rapidity of technological change in genetics is not always
      matched by the uptake of this new knowledge into practice. Increasing genetic
      knowledge has already led to legal liability for those who have not used it
      properly, such as not informing patients or their families of potential genetic
      risk. A similar outcome is also of concern in the case of risk prediction models
      used for hereditary breast cancer. RESULTS: No legal case has directly addressed
      the use of risk prediction models. However, as genetic medicine and risk
      prediction models become more widely used, the prospect of a lawsuit will also
      increase. Current case law is instructive on the circumstances under which
      medical liability actions could be pursued and circumstances under which
      liability is unlikely, such as the provision of faulty family history information
      by a patient. CONCLUSIONS: There is existing case law on family history and
      genetics that parallels in many respects the use of risk prediction models.
      However, the idea of a bad 'prediction' is a difficult legal concept. Outside of
      a plain misuse or failure to use a risk prediction model when circumstances
      clearly required it, there is little legal guidance presently available to
      determine the risk for medical liability.

PMID- 22987125
TI  - Inferred spoligoforest topology unravels spatially bimodal distribution of
      mutations in the DR region.
AB  - Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among
      the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and
      mycobacterium interspersed repetitive unit (MIRU) patterns are commonly used to
      genotype clinical MTBC strains. In this study, we present an evolution model of
      spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of
      spoligotypes. We use a large patient dataset from the United States Centers for
      Disease Control and Prevention (CDC) to generate this model. Based on the
      contiguous deletion assumption and rare observation of convergent evolution, we
      first generate the most parsimonious forest of spoligotypes, called a
      spoligoforest, using three genetic distance measures. An analysis of topological
      attributes of the spoligoforest and number of variations at the direct repeat
      (DR) locus of each strain reveals interesting properties of deletions in the DR
      region. First, we compare our mutation model to existing mutation models of
      spoligotypes and find that our mutation model produces as many within-lineage
      mutation events as other models, with slightly higher segregation accuracy.
      Second, based on our mutation model, the number of descendant spoligotypes
      follows a power law distribution. Third, contrary to prior studies, the power law
      distribution does not plausibly fit to the mutation length frequency. Moreover,
      we find that the total number of mutation events at consecutive spacers follows a
      spatially bimodal distribution. The two modes are spacers 13 and 40, which are
      hotspots for chromosomal rearrangements, and the change point is spacer 34, which
      is absent in most MTBC strains. Based on this observation, we built two
      alternative models for mutation length frequency: the Starting Point Model (SPM)
      and the Longest Block Model (LBM). Both models are plausibly good fits to the
      mutation length frequency distribution, as verified by the goodness-of-fit test.
      We also apply SPM and LBM to a dataset from Institut Pasteur de Guadeloupe and
      verify that these models hold for different strain datasets.

PMID- 22987126
TI  - Estimating functional groups in human gut microbiome with probabilistic topic
      models.
AB  - In this paper, based on the functional elements derived from non-redundant CDs
      catalogue, we show that the configuration of functional groups in meta-genome
      samples can be inferred by probabilistic topic modeling. The probabilistic topic
      modeling is a Bayesian method that is able to extract useful topical information
      from unlabeled data. When used to study microbial samples (assuming that relative
      abundance of functional elements is already obtained by a homology-based
      approach), each sample can be considered as a "document," which has a mixture of
      functional groups, while each functional group (also known as a "latent topic")
      is a weight mixture of functional elements (including taxonomic levels, and
      indicators of gene orthologous groups and KEGG pathway mappings). The functional
      elements bear an analogy with "words." Estimating the probabilistic topic model
      can uncover the configuration of functional groups (the latent topic) in each
      sample. The experimental results demonstrate the effectiveness of our proposed
      method.

PMID- 22987127
TI  - SNP selection and classification of genome-wide SNP data using stratified
      sampling random forests.
AB  - For high dimensional genome-wide association (GWA) case-control data of complex
      disease, there are usually a large portion of single-nucleotide polymorphisms
      (SNPs) that are irrelevant with the disease. A simple random sampling method in
      random forest using default   mtry parameter to choose feature subspace, will
      select too many subspaces without informative SNPs. Exhaustive searching an
      optimal  mtry  is often required in order to include useful and relevant SNPs and
      get rid of vast of non-informative SNPs. However, it is too time-consuming and
      not favorable in GWA for high-dimensional data. The main aim of this paper is to
      propose a stratified sampling method for feature subspace selection to generate
      decision trees in a random forest for GWA high-dimensional data. Our idea is to
      design an equal-width discretization scheme for informativeness to divide SNPs
      into multiple groups. In feature subspace selection, we randomly select the same
      number of SNPs from each group and combine them to form a subspace to generate a
      decision tree. The advantage of this stratified sampling procedure can make sure
      each subspace contains enough useful SNPs, but can avoid a very high
      computational cost of exhaustive search of an optimal  mtry, and maintain the
      randomness of a random forest. We employ two genome-wide SNP data sets (Parkinson
      case-control data comprised of 408 803 SNPs and Alzheimer case-control data
      comprised of 380 157 SNPs) to demonstrate that the proposed stratified sampling
      method is effective, and it can generate better random forest with higher
      accuracy and lower error bound than those by Breiman's random forest generation
      method. For Parkinson data, we also show some interesting genes identified by the
      method, which may be associated with neurological disorders for further
      biological investigations.

PMID- 22987128
TI  - Combined rule extraction and feature elimination in supervised classification.
AB  - There are a vast number of biology related research problems involving a
      combination of multiple sources of data to achieve a better understanding of the
      underlying problems. It is important to select and interpret the most important
      information from these sources. Thus it will be beneficial to have a good
      algorithm to simultaneously extract rules and select features for better
      interpretation of the predictive model. We propose an efficient algorithm,
      Combined Rule Extraction and Feature Elimination (CRF), based on 1-norm
      regularized random forests. CRF simultaneously extracts a small number of rules
      generated by random forests and selects important features. We applied CRF to
      several drug activity prediction and microarray data sets. CRF is capable of
      producing performance comparable with state-of-the-art prediction algorithms
      using a small number of decision rules. Some of the decision rules are
      biologically significant.

PMID- 22987129
TI  - Multilabel learning for protein subcellular location prediction.
AB  - Protein subcellular localization aims at predicting the location of a protein
      within a cell using computational methods. Knowledge of subcellular localization
      of proteins indicates protein functions and helps in identifying drug targets.
      Prediction of 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 are only used to deal with the single-location
      proteins. To better reflect the characteristics of multiplex proteins, we
      formulate prediction of subcellular localization of multiplex proteins as a
      multilabel learning problem. We present and compare two multilabel learning
      approaches, which exploit correlations between labels and leverage label-specific
      features, respectively, to induce a high quality prediction model. Experimental
      results on six protein data sets under various organisms show that our described
      methods achieve significantly higher performance than any of the existing
      methods. Among the different multilabel learning methods, we find that methods
      exploiting label correlations performs better than those leveraging label
      specific features.

PMID- 22987130
TI  - Correlation of genomic features with dynamic modularity in the yeast interactome:
      a view from the structural perspective.
AB  - The idea of the existence of date and party hubs in protein-protein interaction
      networks has been debated since it was proposed in 2004. Based on the
      incorporation of the information extracted from known three-dimensional
      structures of protein interactions, we revisited the properties associated with
      date and party hubs previously identified. The correlation of genomic
      essentiality, gene coexpression, and functional semantic similarity with date and
      party hubs were examined. The number of interaction interfaces associated with
      each hub was taken into account. The results suggested that the identification of
      date and party hubs based on their network connectivity and expression profiles
      with interaction partners may be incomplete. The number of interaction interfaces
      could play an important role in examining functional and topological properties
      associated with each hub protein. The observation is robust to the choice of
      degree cutoffs for hubs. Furthermore, we found that while singlish-interface hubs
      seem to correspond mostly to date hub, it appears that there is no significant
      difference between the proportions of multi-interface proteins categorized as
      date and as party hubs.

PMID- 22987131
TI  - Robust and global delay-dependent stability for genetic regulatory networks with
      parameter uncertainties.
AB  - The study of stability is essential for designing or controlling genetic
      regulatory networks, which can be described by nonlinear differential equations
      with time delays. Much attention has been paid to the study of delay-independent
      stability of genetic regulatory networks and as a result, many sufficient
      conditions have been derived for delay-independent stability. Although it might
      be more interesting in practice, delay-dependent stability of genetic regulatory
      networks has been studied insufficiently. Based on the linear matrix inequality
      (LMI) approach, in this study we will present some delay-dependent stability
      conditions for genetic regulatory networks. Then we extend these results to
      genetic regulatory networks with parameter uncertainties. To illustrate the
      effectiveness of our theoretical results, gene repressilatory networks are
      analyzed .

PMID- 22987132
TI  - Reconstruction of large-scale gene regulatory networks using Bayesian model
      averaging.
AB  - Gene regulatory networks provide the systematic view of molecular interactions in
      a complex living system. However, constructing large-scale gene regulatory
      networks is one of the most challenging problems in systems biology. Also large
      burst sets of biological data require a proper integration technique for reliable
      gene regulatory network construction. Here we present a new reverse engineering
      approach based on Bayesian model averaging which attempts to combine all the
      appropriate models describing interactions among genes. This Bayesian approach
      with a prior based on the Gibbs distribution provides an efficient means to
      integrate multiple sources of biological data. In a simulation study with maximum
      of 2000 genes, our method shows better sensitivity than previous elastic-net and
      Gaussian graphical models, with a fixed specificity of 0.99. The study also shows
      that the proposed method outperforms the other standard methods for a DREAM
      dataset generated by nonlinear stochastic models. In brain tumor data analysis,
      three large-scale networks consisting of 4422 genes were built using the gene
      expression of non-tumor, low and high grade tumor mRNA expression samples, along
      with DNA-protein binding affinity information. We found that genes having a large
      variation of degree distribution among the three tumor networks are the ones that
      see most involved in regulatory and developmental processes, which possibly gives
      a novel insight concerning conventional differentially expressed gene analysis.

PMID- 22987133
TI  - BioVLAB-MMIA: a cloud environment for microRNA and mRNA integrated analysis
      (MMIA) on Amazon EC2.
AB  - MicroRNAs, by regulating the expression of hundreds of target genes, play
      critical roles in developmental biology and the etiology of numerous diseases,
      including cancer. As a vast amount of microRNA expression profile data are now
      publicly available, the integration of microRNA expression data sets with gene
      expression profiles is a key research problem in life science research. However,
      the ability to conduct genome-wide microRNA-mRNA (gene) integration currently
      requires sophisticated, high-end informatics tools, significant expertise in
      bioinformatics and computer science to carry out the complex integration
      analysis. In addition, increased computing infrastructure capabilities are
      essential in order to accommodate large data sets. In this study, we have
      extended the BioVLAB cloud workbench to develop an environment for the integrated
      analysis of microRNA and mRNA expression data, named BioVLAB-MMIA. The workbench
      facilitates computations on the Amazon EC2 and S3 resources orchestrated by the
      XBaya Workflow Suite. The advantages of BioVLAB-MMIA over the web-based MMIA
      system include: 1) readily expanded as new computational tools become available;
      2) easily modifiable by re-configuring graphic icons in the workflow; 3) on
      demand cloud computing resources can be used on an "as needed" basis; 4)
      distributed orchestration supports complex and long running workflows
      asynchronously. We believe that BioVLAB-MMIA will be an easy-to-use computing
      environment for researchers who plan to perform genome-wide microRNA-mRNA (gene)
      integrated analysis tasks.

PMID- 22987134
TI  - ENteric Immunity SImulator: a tool for in silico study of gastroenteric
      infections.
AB  - Clinical symptoms of microbial infection of the gastrointestinal (GI) tract are
      often exacerbated by inflammation induced pathology. Identifying novel avenues
      for treating and preventing such pathologies is necessary and complicated by the
      complexity of interacting immune pathways in the gut, where effector and
      inflammatory immune cells are regulated by anti-inflammatory or regulatory cells.
      Here we present new advances in the development of the ENteric Immunity SImulator
      (ENISI), a simulator of GI immune mechanisms in response to resident commensal
      bacteria as well as invading pathogens and the effect on the development of
      intestinal lesions. ENISI is a tool for identifying potential treatment
      strategies that reduce inflammation-induced damage and, at the same time, ensure
      pathogen removal by allowing one to test plausibility of in vitro observed
      behavior as explanations for observations in vivo, propose behaviors not yet
      tested in vitro that could explain these tissue-level observations, and conduct
      low-cost, preliminary experiments of proposed interventions/treatments. An
      example of such application is shown in which we simulate dysentery resulting
      from Brachyispira hyodysenteriae infection and identify aspects of the host
      immune pathways that lead to continued inflammation-induced tissue damage even
      after pathogen elimination.

PMID- 22987135
TI  - [Catecholaminergic polymorphic ventricular tachycardia].
AB  - Catecholaminergic polymorphic ventricular tachycardia (PCVT) is a rare,
      congenital ventricular tachyarrhythmia which occurs in the setting of adrenergic
      activation. It potentially leads to syncope and/or sudden cardiac death (SCD).
      PCVT represents one of the most dangerous congenital ion channel diseases.
      Mutations of the ryanodine receptor gene (RYR2), the calsequestrin gene (CASQ2),
      and the triadin gene (TRDN) have been identified as an underlying correlate. beta
      Blockers are employed as therapy and are sometimes combined with class IC
      antiarrhythmic drugs, or calcium antagonists of the verapamil type. ICD
      implantation is recommended in case of persisting syncope in the presence of beta
      blocker therapy or survived SCD. Left thoracic sympathectomy represents a
      subsidiary interventional therapy for individual cases. In addition,
      modifications of the patient's lifestyle including avoidance of physical stress
      and heart rates> 120/min are recommended.

PMID- 22987136
TI  - A comparative study between amiodarone and magnesium sulfate as antiarrhythmic
      agents for prophylaxis against atrial fibrillation following lobectomy.
AB  - PURPOSE: Atrial fibrillations are common after thoracic surgery. Amiodarone and
      magnesium sulfate have been used for the management of atrial fibrillation
      following cardiac and non-cardiac surgery. However, to our knowledge, comparisons
      of both drugs with each other and with a control group in relation to the
      prevention of AF following lung surgery have not been performed. Our primary aim
      in this study was to prospectively evaluate the prophylactic effects of magnesium
      sulfate and amiodarone used separately and compare them with a control group
      analyzed retrospectively during and following lobectomy surgeries. PATIENTS AND
      METHODS: The prophylactic value of amiodarone (group A; 219 patients)
      administered as an intravenous infusion (15 mg/kg for 48 h postoperatively) after
      a loading dose (5 mg/kg) was compared with magnesium sulfate (group M; 219
      patients) administered intravenously as a loading dose (80 mg/kg magnesium
      sulfate over 30 min preoperatively) and then as an intravenous infusion (8
      mg/kg/h for 48 h) in 438 patients undergoing lobectomy. These two groups were
      compared with a control group of 219 patients who were analyzed retrospectively.
      RESULTS: The results showed significantly lower incidences of AF in groups A and
      M when compared with group C (P < 0.05). There was no significant difference
      between the amiodarone and magnesium sulfate groups. However, the incidence of
      postoperative AF was lower in the amiodarone group, where only 21 (10 %) patients
      developed AF in comparison to 27 (12.5 %) patients in the magnesium sulfate
      group. Group C showed a higher incidence, 44 (20.5 %) patients, when compared
      with both groups. In addition, there were significant differences between the
      three groups concerning intensive care unit (ICU) and total hospital stays (P <
      0.05). CONCLUSION: Our study showed that during the intra- and postoperative
      periods, both amiodarone and magnesium sulfate are effective at preventing the
      incidence of atrial fibrillation following lung resection surgery in comparison
      to the control group.

PMID- 22987137
TI  - The effect of osteochondral regeneration using polymer constructs and continuous
      passive motion therapy in the lower weight-bearing zone of femoral trocheal
      groove in rabbits.
AB  - Remedying patellofemoral osteochondral defects using clinical therapy remains
      challenging. Construct-based and cell-based regenerative medicine with in vitro
      physical stimuli has been progressively implemented. However, the effect of
      physical stimuli in situ in knee joints with degradable constructs is still not
      well-documented. Therefore, we studied whether it was practical to achieve
      articular cartilage repair using a poly(lactic-co-glycolic acid) (PLGA) construct
      in addition to early short-term continuous passive motion (CPM) for treatment of
      full-thickness osteochondral defects in the lower-weigh bearing (LWB) zone of the
      femoral trocheal groove. Twenty-six rabbits were randomly allocated into either
      intermittent active motion (IAM) or CPM treatment groups with or without PLGA
      constructs, termed PLGA construct-implanted (PCI) and empty defect knee models,
      respectively. Gross observation, histology, inflammatory cells, which were
      identified using H&E staining, total collagen and alignment, studied
      qualitatively using Masson's trichrome staining, glycosaminoglycan (GAG),
      identified using Alcian blue staining, and newly formed bone, observed using
      micro-CT, were evaluated at 4 and 12 weeks after surgery. Repair of osteochondral
      defects in the PCI-CPM group was more promising than all other groups. The better
      osteochondral defect repair in the PCI-CPM group corresponded to smooth cartilage
      surfaces, no inflammatory reaction, hyaline cartilaginous tissues composition,
      sound collagen alignment with positive collagen type II expression, higher GAG
      content, mature bone regeneration with osteocyte, clear tidemark formation, and
      better degradation of PLGA. In summary, the use of a simple PLGA construct
      coupled with passive motion promotes positive healing and may be a promising
      clinical intervention for osteochondral regeneration in LWB defects.

PMID- 22987138
TI  - Crystal and electronic structures of metallic Ba2Pd5Ge4.
AB  - Crystals of a new intermetallic germanide Ba(2)Pd(5)Ge(4) have been grown out of
      a binary PdGe flux. Single crystal X-ray diffraction reveals that the compound
      crystallizes in a novel structure type in the Cmca space group, with a =
      10.9296(9) A, b = 14.1639(12) A, and c = 5.8808(5) A at 173(2) K. This structure
      type features a three-dimensional [Pd(5)Ge(4)] network made of distorted
      tetrahedral and square planar PdGe(4) units, with Ba atoms filling the voids. The
      magnetic susceptibility and the electrical resistivity measurements show that
      Ba(2)Pd(5)Ge(4) is a Pauli paramagnet and a metal with the room temperature
      resistivity value of rho(300 K) ~ 0.096 mOmega cm. The band structure
      calculations confirm that Ba(2)Pd(5)Ge(4) is a good metal with no magnetic
      instability.

PMID- 22987139
TI  - Influence of stearic acids on resveratrol-HSA interaction.
AB  - The interaction between the natural polyphenol resveratrol and human serum
      albumin (HSA), the most abundant transport protein in plasma, has been studied in
      the absence and in the presence of up to six molecules of stearic acids (SA) pre
      complexed with the protein. The study has been carried out by using the intrinsic
      fluorescence of both HSA and resveratrol. Protein and polyphenol fluorescence
      data indicate that resveratrol binds to HSA with an association constant k(a) =
      (1.10 +/- 0.14) * 10(5) M(-1) and (1.09 +/- 0.02) * 10(5) M(-1), respectively,
      whereas Job plot evidences the formation of an equimolar protein/drug complex.
      Low SA content associated with HSA does not affect significantly the structural
      conformation of the protein and its interaction with resveratrol, whereas high SA
      content induces conformational changes in the protein, and reduces resveratrol
      binding affinity. The photostability of resveratrol in the different samples
      changes in the order: buffer < (high [SA]/HSA) < HSA < (low [SA]/HSA). The
      results on (SA/HSA)-resveratrol samples highlight the ability of the protein to
      bind hydrophobic and amphiphilic ligands and to protect from degradation an
      important antioxidant molecule under biologically relevant conditions.

PMID- 22987140
TI  - Procedure for fabricating biofunctional nanofibers.
AB  - Electrospinning is an effective processing method for preparing nanofibers
      decorated with functional groups. Nanofibers decorated with functional groups may
      be utilized to study material-biomarker interactions i.e. act as biosensors with
      potential as single molecule detectors. We have developed an effective approach
      for preparing functional polymers where the functionality has the capacity of
      specifically binding with a model protein. In our model system, the functional
      group is 2,4-dinitrophenyl (DNP) and the protein is anti-DNP IgE (Immunoglobulin
      E). The functional polymer, alpha,omega-bi[2,4-dinitrophenyl
      caproic][poly(ethylene oxide)-b-poly(2-methoxystyrene)-b-poly(ethylene oxide)]
      (CDNP-PEO-P2MS-PEO-CDNP), is prepared by anionic living polymerization. The
      difunctional initiator utilized in the polymerization was prepared by electron
      transfer reaction of alpha-methylstyrene and potassium (mirror) metal. The 2
      methoxystyrene monomer was added first to the initiator, followed by the addition
      of the second monomer, ethylene oxide, and finally the living polymer was
      terminated by methanol. The alpha,omega-dihydroxyl polymer [HO-PEO-P2MS-PEO-OH]
      was reacted with N-2,4-DNP-?-amino caproic acid, by DCC coupling, resulting in
      the formation of alpha,omega-bi[2,4-dinitrophenylcaproic][poly(ethyleneoxide)-b
      poly(2-methoxystyrene)-b-poly(ethylene oxide)] (CDNP-PEO-P2MS-PEO-CDNP). The
      polymers were characterized by FT-IR, (1)H NMR and Gel Permeation Chromatography
      (GPC). The molecular weight distributions of the polymers were narrow (1.1-1.2)
      and polymers with molecular weights greater than 50,000 was used in this study.
      The polymers were yellow powders and soluble in tetrahydrofuran. A water soluble
      CDNP-PEO-P2MS-PEO-CDNP/ DMEG (dimethoxyethylene glycol) complex binds and
      achieves steady state binding with solution IgE within a few seconds. Higher
      molecular weight (water insoluble i.e. around 50,000) CDNP-PEO-P2MS-PEO-CDNP
      polymers, containing 1% single wall carbon nanotubes (SWCNT) were processed into
      electroactive nanofibers (100 nm to 500 nm in diameter) on silicon substrate.
      Fluorescence spectroscopy shows that anti-DNP IgE interacts with the nanofibers
      by binding with the DNP functional groups decorating the fibers. These
      observations suggest that appropriately functionalized nanofibers hold promise
      for developing biomarker detection device.

PMID- 22987141
TI  - Comparing kidney transplant outcomes; caveats and lessons.

PMID- 22987143
TI  - Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy
      interruption for gastrointestinal tract bleeding.
AB  - BACKGROUND: Patients who not only survive a warfarin-associated gastrointestinal
      tract bleeding (GIB) event but also have an ongoing risk for thromboembolism
      present 2 clinical dilemmas: whether and when to resume anticoagulation. The
      objective of this study was to determine the incidence of thrombosis, recurrent
      GIB, and death, as well as the time to resumption of anticoagulant therapy,
      during the 90 days following a GIB event. METHODS: In this retrospective, cohort
      study using administrative and clinical databases, patients experiencing GIB
      during warfarin therapy were categorized according to whether they resumed
      warfarin therapy after GIB and followed up for 90 days. Variables describing the
      management and severity of the index GIB were also collected. Kaplan-Meier curves
      were constructed to estimate the survival function of thrombosis, recurrent GIB,
      and death between the "resumed warfarin therapy" and "did not resume warfarin
      therapy" groups, with Cox proportional hazards modeling to adjust for potentially
      confounding factors. RESULTS: There were 442 patients with warfarin-associated
      index GIB included in the analyses. Following the index GIB, 260 patients (58.8%)
      resumed warfarin therapy. Warfarin therapy resumption after the index GIB was
      associated with a lower adjusted risk for thrombosis (hazard ratio [HR], 0.05;
      95% CI, 0.01-0.58) and death (HR, 0.31; 95% CI, 0.15-0.62), without significantly
      increasing the risk for recurrent GIB (HR, 1.32; 95% CI, 0.50-3.57). CONCLUSIONS:
      The decision to not resume warfarin therapy in the 90 days following a GIB event
      is associated with increased risk for thrombosis and death. For many patients who
      have experienced warfarin-associated GIB, the benefits of resuming anticoagulant
      therapy will outweigh the risks.

PMID- 22987142
TI  - Low- and high-molecular-weight urinary proteins as predictors of response to
      rituximab in patients with membranous nephropathy: a prospective study.
AB  - BACKGROUND: Selective urinary biomarkers have been considered superior to total
      proteinuria in predicting response to treatment and outcome in patients with
      membranous nephropathy (MN). METHODS: We prospectively tested whether urinary (U)
      excretion of retinol-binding protein (RBP), alpha1-microglobulin (alpha1M),
      albumin, immunoglobulin IgG and IgM and/or anti-phospholipase 2 receptor
      (PLA(2)R) levels could predict response to rituximab (RTX) therapy better than
      standard measures in MN. We also correlated changes in antibodies to PLA(2)R with
      these urinary biomarkers. RESULTS: Twenty patients with MN and proteinuria (P) >5
      g/24 h received RTX (375 mg/m(2) * 4) and at 12 months, 1 patient was in complete
      remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR)
      and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in
      1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at
      baseline (mg/24 h) was a significant predictor of change in proteinuria at 12
      months (Delta urinary protein) (P = 0.04). In addition, fractional excretion (FE)
      of IgG, urinary alpha 1 microglobulin (Ualpha1M) (mg/24 h) and URBP (MUg/24 h)
      were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the
      other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P =
      0.10, 0.27, 0.22 and 0.20, respectively). However, when results were analyzed in
      relation to proteinuria at 24 months, none of the U markers that predicted
      response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20).
      Decline in anti-PLA(2)R levels was associated with and often preceded urinary
      biomarker response but positivity at baseline was not a predictor of proteinuria
      response. CONCLUSIONS: The results suggest that in patients with MN,
      quantification of low-, medium- and high-molecular-weight urinary proteins may be
      associated with rate of response to RTX, but do not correlate with longer term
      outcomes.

PMID- 22987144
TI  - Patient-reported outcomes in randomized clinical trials: development of ISOQOL
      reporting standards.
AB  - PURPOSE: To develop expert consensus on a suite of reporting standards for HRQL
      outcomes of RCTs. METHODS: A Task Force of The International Society of Quality
      of Life Research (ISOQOL) undertook a systematic review of the literature to
      identify candidate reporting standards for HRQL in RCTs. Subsequently, a web
      based survey was circulated to the ISOQOL membership. Respondents were asked to
      rate candidate standards on a 4-point Likert scale based on their perceived value
      in reporting studies in which HRQL was a study outcome (primary or secondary).
      Results were synthesized into draft reporting guidelines, which were further
      reviewed by the membership to inform the final guidance. RESULTS: Forty-six
      existing candidate standards for reporting HRQL results in RCTs were synthesized
      to produce a 40 item survey that was completed electronically by 161 respondents.
      The majority of respondents rated all 40 items to be either 'essential' or
      'desirable' when HRQL was a primary RCT outcome. Ratings changed when HRQL was a
      secondary study outcome. Feedback on the survey findings resulted in the Task
      Force generalizing the guidance to include patient-reported outcomes (PROs). The
      final guidance, which recommends standards for use in reporting PROs generally,
      and more specifically, for PROs identified as primary study outcomes, was
      approved by the ISOQOL Board of Directors. CONCLUSIONS: ISOQOL has developed a
      suite of recommended standards for reporting PRO results of RCTs. Improved
      reporting of PROs will enable accurate interpretation of evidence to inform
      patient choice, aid clinical decision making, and inform health policy.

PMID- 22987146
TI  - Photochemical generation of oxa-dibenzocyclooctyne (ODIBO) for metal-free click
      ligations.
AB  - Oxa-dibenzocyclooctynes (ODIBO, 2a-c) are prepared by photochemical
      decarbonylation of corresponding cyclopropenones (photo-ODIBO, 1a-c). While photo
      ODIBO does not react with azides, ODIBO is one of the most reactive cyclooctynes
      exhibiting rates of cycloaddition over 45 M(-1) s(-1) in aqueous solutions. ODIBO
      is stable under ambient conditions and has low reactivity towards thiols. Photo
      ODIBO survives heating up to 160  degrees C and does not react with thiols.

PMID- 22987145
TI  - Assessment of proximal outcomes of self-management programs: translation and
      psychometric evaluation of a German version of the Health Education Impact
      Questionnaire (heiQTM).
AB  - PURPOSE: This paper describes the translation, cultural adaption, and
      psychometric evaluation of a German version of the Health Education Impact
      Questionnaire (heiQTM), a widely used generic instrument assessing a wide range
      of proximal outcomes of self-management programs. METHODS: The translation was
      carried out according to international standards and included forward and
      backward translations. Comprehensibility and content validity were tested using
      cognitive interviews with 10 rehabilitation inpatients. Psychometric properties
      were examined in rehabilitation inpatients (n = 1,202) with a range of chronic
      conditions. Factorial validity was assessed using confirmatory factor analysis;
      concurrent validity was explored by correlations with comparator scales. RESULTS:
      The items of the German heiQTM were well understood by rehabilitation inpatients.
      The structure of the eight heiQTM scales was replicated after minor adjustment.
      heiQTM scales had higher correlations with comparator scales with similar
      constructs, particularly mental health concepts than with physical health.
      Moreover, all heiQTM scales differentiated between individuals across different
      levels of depression. CONCLUSION: The German heiQTM is comprehensible for German
      speaking patients suffering from different types of chronic conditions; it
      assesses relevant outcomes of self-management programs in a reliable and valid
      manner. Further studies involving its practical application are warranted.

PMID- 22987147
TI  - Evaluation of a prospective surgical strategy of extended resection to achieve R0
      status in gall bladder cancer.
AB  - INTRODUCTION: Radical resection to achieve R0 status remains the only potential
      curative option in patients with gall bladder cancer (GBC). This study was aimed
      to evaluate the efficacy of an extended criterion of radical resection to achieve
      R0 status in GBC. METHODS: A triple-phase CT with 3D reconstruction was done in
      all patients. A standard resectability criterion was followed in all patients. A
      minimum of liver segment 4B + 5 resection and radical lymphadenectomy including
      the para-aortic areas were undertaken in all patients. Adjacent organectomy was
      added as required. RESULTS: Between November 2008 and April 2011, 59 patients
      with GBC underwent operation and 40 (resectability, 68 %) underwent resection.
      The resectional procedures performed were segmentectomy 4B + 5 in 31 (78 %),
      median sectorectomy in 2 (5 %), extended right hepatectomy in 3 (8 %), and
      hepatopancreaticoduodenectomy in 4 (10 %) patients. Postoperative complications
      occurred in 24 (60 %) patients. Two patients died postoperatively. A total of 829
      lymph nodes were harvested and the median lymph node count was 18 (4-77). Twenty
      three (58 %) patients had lymph node metastases. Twenty-eight of 40 (70 %) had
      disease limited till N1 nodes. Metastases up to N2 lymph nodes were seen in 12
      (30 %). American Joint Committee on Cancer seventh edition stages were I-2 (5 %)
      patients, II-5 (13 %), III-19 (48 %), and IV-14 (35 %). R0 resection was achieved
      in 33 (83 %) patients. Four patients had recurrence and one died of recurrence.
      All other patients are alive till the last follow-up. CONCLUSIONS: Assessment
      with triple-phase CT with 3D reconstruction can produce high resectability rate
      in GBC. Extended criterion of radical resection results in R0 status in more than
      80 % of patients with GBC.

PMID- 22987148
TI  - False external feedback modulates posterror slowing and the f-P300: implications
      for theories of posterror adjustment.
AB  - People tend to slow down after mistakes. This posterror slowing (PES) has
      commonly been explained by a change to a more conservative response threshold to
      avoid future errors. Alternatively, the attention-orienting account posits that
      all infrequent, surprising events (including errors) elicit an orienting response
      followed by a time-consuming process of task reorientation, explaining PES
      without increased response caution. In the present study, we employed both
      behavioral and electrophysiological measures to compare the predictions of these
      accounts using a flanker paradigm in which accurate or false external response
      feedback was provided. Participants demonstrated typical posterror adjustments,
      responding more slowly and accurately in posterror than in postcorrect trials.
      This finding provides initial evidence suggesting that posterror adjustments are
      motivated by the avoidance of subsequent mistakes. Most importantly, PES and an
      event-related potential relating to the attentional processing of feedback, the
      feedback-related P300 (f-P300), were modulated by feedback type. More
      specifically, the f-P300 was larger after false than after accurate feedback,
      suggesting that participants oriented their attention toward (i.e., were
      surprised by) inaccurate feedback signals. Interestingly, false feedback
      differentially modulated reaction times: Participants were slower after correct
      responses when feedback falsely informed of an error rather than confirmed the
      correct response. In contrast, faster responses were made after errors when
      feedback falsely indicated correct rather than incorrect performance. When these
      patterns of results are regarded together, they are best explained by theories of
      cognitive control in which posterror adjustments in choice reaction time tasks
      are assumed to reflect control processes leading to more conservative performance
      after error signals.

PMID- 22987149
TI  - Hypoxia and gerosuppression: the mTOR saga continues.
AB  - Growth-promoting and nutrient/mitogen-sensing pathways such as mTOR convert p21-
      and p16-induced arrest into senescence (geroconversion). We have recently
      demonstrated that hypoxia, especially near-anoxia, suppresses geroconversion.
      This gerosuppressive effect of hypoxia correlated with inhibition of the mTOR/S6K
      pathway but not with modulation of the LKB1/AMPK/eEF2 pathway. Here we further
      show that mTOR inhibition is required for gerosuppression by hypoxia, at least in
      some cellular models, because depletion of TSC2 abolished mTOR inhibition and
      gerosupression by hypoxia. Also, in two cancer cell lines resistant to inhibition
      of mTOR by both p53 and hypoxia, hypoxia did not suppress geroconversion.
      Therefore, the effects of hypoxia on the oxygen-sensing mTOR pathway and
      geroconversion are cell type-specific. We also briefly discuss replicative
      senescence, organismal aging and free radical theory.

PMID- 22987150
TI  - Understanding the origins of UV-induced recombination through manipulation of
      sister chromatid cohesion.
AB  - Ultraviolet light (UV) can provoke genome instability, partly through its ability
      to induce homologous recombination (HR). However, the mechanism(s) of UV-induced
      recombination is poorly understood. Although double-strand breaks (DSBs) have
      been invoked, there is little evidence for their generation by UV. Alternatively,
      single-strand DNA lesions that stall replication forks could provoke
      recombination. Recent findings suggest efficient initiation of UV-induced
      recombination in G1 through processing of closely spaced single-strand lesions to
      DSBs. However, other scenarios are possible, since the recombination initiated in
      G1 can be completed in the following stages of the cell cycle. We developed a
      system that could address UV-induced recombination events that start and finish
      in G2 by manipulating the activity of the sister chromatid cohesion complex. Here
      we show that sister-chromatid cohesion suppresses UV-induced recombination events
      that are initiated and resolved in G2. By comparing recombination frequencies and
      survival between UV and ionizing radiation, we conclude that a substantial
      portion of UV-induced recombination occurs through DSBs. This notion is supported
      by a direct physical observation of UV-induced DSBs that are dependent on
      nucleotide excision repair. However, a significant role of nonDSB intermediates
      in UV-induced recombination cannot be excluded.

PMID- 22987151
TI  - The real face of HIF1alpha in the tumor process.
AB  - It is well known that the hypoxia-inducible factor 1 alpha (HIF1alpha) is
      detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1alpha is
      detectable even under normoxic conditions, if the metabolism is altered, e.g.,
      high proliferation index. Importantly, both hypoxic metabolism and the Warburg
      effect have in common a decrease of the intracellular pH value. In our
      interpretation, HIF1alpha is not directly accumulated by hypoxia, but by a
      process which occurs always under hypoxic conditions, a decrease of the
      intracellular pH value because of metabolic imbalances. We assume that HIF1alpha
      is a sensitive controller of the intracellular pH value independently of the
      oxygen concentration. Moreover, HIF1alpha has its major role in activating genes
      to eliminate toxic metabolic waste products (e.g., NH3/NH4+) generated by the
      tumor-specific metabolism called glutaminolysis, which occur during hypoxia, or
      the Warburg effect. For that reason, HIF1alpha appears as a potential target for
      tumor therapy to disturb the pH balance and to inhibit the elimination of toxic
      metabolic waste products in the tumor cells.

PMID- 22987154
TI  - Level of cdk5 expression predicts the survival of relapsed multiple myeloma
      patients.

PMID- 22987152
TI  - Local and global functions of Timeless and Tipin in replication fork protection.
AB  - The eukaryotic cell replicates its chromosomal DNA with almost absolute fidelity
      in the course of every cell cycle. This accomplishment is remarkable considering
      that the conditions for DNA replication are rarely ideal. The replication
      machinery encounters a variety of obstacles on the chromosome, including damaged
      template DNA. In addition, a number of chromosome regions are considered to be
      difficult to replicate owing to DNA secondary structures and DNA binding proteins
      required for various transactions on the chromosome. Under these conditions,
      replication forks stall or break, posing grave threats to genomic integrity. How
      does the cell combat such stressful conditions during DNA replication? The
      replication fork protection complex (FPC) may help answer this question. Recent
      studies have demonstrated that the FPC is required for the smooth passage of
      replication forks at difficult-to-replicate genomic regions and plays a critical
      role in coordinating multiple genome maintenance processes at the replication
      fork.

PMID- 22987155
TI  - [Prevention and treatment of venous thromboembolism in patients with cancer].

PMID- 22987157
TI  - Remembering the past and imagining the future in the elderly.
AB  - Recent research has demonstrated commonalities between remembering past events
      and imagining future events. Behavioral studies have revealed that remembering
      the past and imagining the future depend on shared cognitive processes, whereas
      neuropsychological and neuroimaging studies have shown that many of the same
      brain regions are involved in both remembering the past and imagining the future.
      Here, we review recent cognitive and neuroimaging studies that examine
      remembering the past and imagining the future in elderly adults. These studies
      document significant changes in elderly adults' capacities to imagine future
      events that are correlated with their memory deficits; most strikingly, older
      adults tend to remember the past and imagine the future with less episodic detail
      than younger adults. These findings are in line with the constructive episodic
      simulation hypothesis [Schacter and Addis: Phil Trans R Soc B 2007;362:773-786],
      which holds that past and future events draw on similar information and rely on
      similar underlying processes, and that episodic memory supports the construction
      of future events by extracting and recombining stored information into a
      simulation of a novel event. At the same time, however, recent data indicate that
      non-episodic factors also contribute to age-related changes in remembering the
      past and imagining the future. We conclude by considering a number of questions
      and challenges concerning the interpretation of age-related changes in
      remembering and imagining, as well as functional implications of this research
      for everyday concerns of older adults.

PMID- 22987153
TI  - DNA2 and EXO1 in replication-coupled, homology-directed repair and in the
      interplay between HDR and the FA/BRCA network.
AB  - During DNA replication, stalled replication forks and DSBs arise when the
      replication fork encounters ICLs (interstrand crosslinks), covalent protein/DNA
      intermediates or other discontinuities in the template. Recently, homologous
      recombination proteins have been shown to function in replication-coupled repair
      of ICLs in conjunction with the Fanconi anemia (FA) regulatory factors FANCD2
      FANCI, and, conversely, the FA gene products have been shown to play roles in
      stalled replication fork rescue even in the absence of ICLs, suggesting a broader
      role for the FA network than previously appreciated. Here we show that DNA2
      helicase/nuclease participates in resection during replication-coupled repair of
      ICLs and other replication fork stresses. DNA2 knockdowns are deficient in HDR
      (homology-directed repair) and the S phase checkpoint and exhibit genome
      instability and sensitivity to agents that cause replication stress. DNA2 is
      partially redundant with EXO1 in these roles. DNA2 interacts with FANCD2, and
      cisplatin induces FANCD2 ubiquitylation even in the absence of DNA2. DNA2 and
      EXO1 deficiency leads to ICL sensitivity but does not increase ICL sensitivity in
      the absence of FANCD2. This is the first demonstration of the redundancy of human
      resection nucleases in the HDR step in replication-coupled repair, and suggests
      that DNA2 may represent a new mediator of the interplay between HDR and the
      FA/BRCA pathway.

PMID- 22987158
TI  - Accuracy of lower cervical pedicle screw placement with assistance of distinct
      navigation systems: a human cadaveric study.
AB  - PURPOSE: Evaluate the accuracy of five different techniques for lower cervical
      pedicle screw placement. METHODS: Forty human cadaveric cervical spines were
      equally divided into five groups, and each group had eight specimens. Pedicle
      screws with dia. 3.5 mm were used. Group 1 was blind screw placement without any
      assistance; Group 2-5 was assisted by the X-ray fluoroscopy, virtual fluoroscopy
      navigation system, CT-based navigation system, and Iso-C 3D navigation system,
      respectively. Thereafter, cortical integrity of each pedicle was evaluated by
      anatomic dissection of the specimens. RESULTS: A total of 398 pedicle screws were
      inserted. In the Group 1-5, the average operation time per sample was 27 +/- 3.0,
      112 +/- 10.3, 69 +/- 6.4, 98 +/- 11.0, and 91 +/- 6.0 min, respectively. The
      outcome for excellent, fair and poor were 29 (36.3 %), 21 (26.2 %) and 30 (37.5
      %) in Group 1; 35 (44.9 %), 29 (37.2 %) and 14 (17.9 %) in Group 2; 34 (42.5 %),
      36 (45.0 %) and 10 (12.5 %) in Group 3; 70 (87.5 %), 10 (12.5 %) and 0 (0.0 %) in
      Group 4; 72 (90.0 %), 8 (10.0 %) and 0 (0.0 %) in Group 5. CONCLUSIONS: Blind
      screw placement was surely unsafe. Lower cervical pedicle screw placement
      assisted by the CT-based navigation system or the Iso-C 3D navigation system
      significantly improved the accuracy compared to the fluoroscopy assistance and
      the virtual fluoroscopy navigation assistance.

PMID- 22987160
TI  - Nutrition: Reduce calories, live longer?

PMID- 22987162
TI  - What you hear is what you get.

PMID- 22987163
TI  - Benchmarks for international surgery.

PMID- 22987159
TI  - Rate of neonatal weight gain and effects on adult metabolic health.
AB  - The association of rapid weight gain in early life with increased adiposity and
      obesity in later life has been established, whereas whether rapid neonatal weight
      gain predisposes individuals to other risk factors for cardiovascular disease and
      type 2 diabetes mellitus remains controversial. Gain in weight of >0.5 SD scores
      in the first 3 months of life (described as rapid weight gain) is associated with
      an unfavourable health profile in adulthood, and keeping weight gain below this
      threshold could reduce the risk of cardiovascular and metabolic diseases later in
      life. Weight gain above this threshold is not necessarily unhealthy if the
      increase is in proportion with the increase in length. As such, regular
      measurement of both the weight and length of all infants is important. Preterm
      infants and those who are born small for gestational age are most likely to have
      rapid weight gain, and are high-risk populations for unfavourable health profiles
      in adulthood.

PMID- 22987164
TI  - Brief tool to measure risk-adjusted surgical outcomes in resource-limited
      hospitals.
AB  - OBJECTIVES: To develop and validate a risk-adjusted tool with fewer than 10
      variables to measure surgical outcomes in resource-limited hospitals. DESIGN: All
      National Surgical Quality Improvement Program (NSQIP) preoperative variables were
      used to develop models to predict inpatient mortality. The models were built by
      sequential addition of variables selected based on their area under the receiver
      operator characteristic curve (AUROC) and externally validated using data based
      on medical record reviews at 1 hospital outside the data set. SETTING Model
      development was based on data from the NSQIP from 2005 to 2009. Validation was
      based on data from 1 nonurban hospital in the United States from 2009 to 2010.
      PATIENTS: A total of 631 449 patients in NSQIP and 239 patients from the
      validation hospital. MAIN OUTCOME MEASURES: The AUROC value for each model.
      RESULTS: The AUROC values reached higher than 90% after only 3 variables
      (American Society of Anesthesiologists class, functional status at time of
      surgery, and age). The AUROC values increased to 91% with 4 variables but did not
      increase significantly with additional variables. On validation, the model with
      the highest AUROC was the same 3-variable model (0.9398). CONCLUSIONS: Fewer than
      6 variables may be necessary to develop a risk-adjusted tool to predict inpatient
      mortality, reducing the cost of collecting variables by 95%. These variables
      should be easily collectable in resource-poor settings, including low- and middle
      income countries, thus creating the first standardized tool to measure surgical
      outcomes globally. Research is needed to determine which of these limited
      variable models is most appropriate in a variety of clinical settings.

PMID- 22987165
TI  - NSQIP lite: a potential tool for global comparative effectiveness evaluations.

PMID- 22987167
TI  - Thyroid cancer operations for obese patients: the bad news and the good news.

PMID- 22987168
TI  - Radiologic evaluation of alternative sites for needle decompression of tension
      pneumothorax.
AB  - OBJECTIVE: To compare the distance to be traversed during needle thoracostomy
      decompression performed at the second intercostal space (ICS) in the
      midclavicular line (MCL) with the fifth ICS in the anterior axillary line (AAL).
      DESIGN: Patients were separated into body mass index (BMI) quartiles, with BMI
      calculated as weight in kilograms divided by height in meters squared. From each
      BMI quartile, 30 patients were randomly chosen for inclusion in the study on the
      basis of a priori power analysis (n = 120). Chest wall thickness on computed
      tomography at the second ICS in the MCL was compared with the fifth ICS in the
      AAL on both the right and left sides through all BMI quartiles. SETTING: Level I
      trauma center. PATIENTS: Injured patients aged 16 years or older evaluated from
      January 1, 2009, to January 1, 2010, undergoing computed tomography of the chest.
      RESULTS: A total of 680 patients met the study inclusion criteria (81.5% were
      male and mean age was 41 years [range, 16-97 years]). Of the injuries sustained,
      13.2% were penetrating, mean (SD) Injury Severity Score was 15.5 (10.3), and mean
      BMI was 27.9 (5.9) (range, 15.4-60.7). The mean difference in chest wall
      thickness between the second ICS at the MCL and the fifth ICS at the AAL was 12.9
      mm (95% CI, 11.0-14.8; P < .001) on the right and 13.4 mm (95% CI, 11.4-15.3; P <
      .001) on the left. There was a stepwise increase in chest wall thickness across
      all BMI quartiles at each location of measurement. There was a significant
      difference in chest wall thickness between the second ICS at the MCL and the
      fifth ICS at the AAL in all quartiles on both the right and the left. The
      percentage of patients with chest wall thickness greater than the standard 5-cm
      decompression needle was 42.5% at the second ICS in the MCL and only 16.7% at the
      fifth ICS in the AAL. CONCLUSIONS: In this computed tomography-based analysis of
      chest wall thickness, needle thoracostomy decompression would be expected to fail
      in 42.5% of cases at the second ICS in the MCL compared with 16.7% at the fifth
      ICS in the AAL. The chest wall thickness at the fifth ICS AAL was 1.3 cm thinner
      on average and may be a preferred location for needle thoracostomy decompression.

PMID- 22987169
TI  - The death of another sacred cow: comment on "radiologic evaluation of alternative
      sites for needle decompression of tension pneumothorax".

PMID- 22987172
TI  - When pNETs bust out of their shells.

PMID- 22987171
TI  - Lymph nodes and survival in pancreatic neuroendocrine tumors.
AB  - HYPOTHESIS: Lymph node metastases decrease survival in patients with pancreatic
      neuroendocrine tumors (pNETs). DESIGN: Prospective database searches. SETTING:
      National Institutes of Health (NIH) and Stanford University Hospital (SUH).
      PATIENTS: A total of 326 patients underwent surgical exploration for pNETs at the
      NIH (n = 216) and SUH (n = 110). MAIN OUTCOME MEASURES: Overall survival, disease
      related survival, and time to development of liver metastases. RESULTS: Forty
      patients (12.3%) underwent enucleation and 305 (93.6%) underwent resection. Of
      the patients who underwent resection, 117 (35.9%) had partial pancreatectomy and
      30 (9.2%) had a Whipple procedure. Forty-one patients also had liver resections,
      21 had wedge resections, and 20 had lobectomies. Mean follow-up was 8.1 years
      (range, 0.3-28.6 years). The 10-year overall survival for patients with no
      metastases or lymph node metastases only was similar at 80%. As expected,
      patients with liver metastases had a significantly decreased 10-year survival of
      30% (P < .001). The time to development of liver metastases was significantly
      reduced for patients with lymph node metastases alone compared with those with
      none (P < .001). For the NIH cohort with longer follow-up, disease-related
      survival was significantly different for those patients with no metastases, lymph
      node metastases alone, and liver metastases (P < .001). Extent of lymph node
      involvement in this subgroup showed that disease-related survival decreased as a
      function of the number of lymph nodes involved (P = .004). CONCLUSIONS: As
      expected, liver metastases decrease survival of patients with pNETs. Patients
      with lymph node metastases alone have a shorter time to the development of liver
      metastases that is dependent on the number of lymph nodes involved. With
      sufficient long-term follow-up, lymph node metastases decrease disease-related
      survival. Careful evaluation of number and extent of lymph node involvement is
      warranted in all surgical procedures for pNETs.

PMID- 22987173
TI  - General surgery resident remediation and attrition: a multi-institutional study.
AB  - OBJECTIVE: To determine the rates and predictors of remediation and attrition
      among general surgery residents. DESIGN, SETTING, AND PARTICIPANTS: Eleven-year
      retrospective analysis of 348 categorical general surgery residents at 6 West
      Coast programs. MAIN OUTCOME MEASURES: Rates and predictors of remediation and
      attrition. RESULTS: Three hundred forty-eight categorical general surgery
      residents were included. One hundred seven residents (31%) required remediation,
      of which 27 were remediated more than once. Fifty-five residents (15.8%) left
      their programs, although only 2 were owing to failed remediation. Remediation was
      not a predictor of attrition (20% attrition for those remediated vs 15% who were
      not [P = .40]). Remediation was most frequently initiated owing to a deficiency
      in medical knowledge (74%). Remediation consisted of monthly meetings with
      faculty (79%), reading assignments (72%), required conferences (27%), therapy
      (12%), and repeating a clinical year (6.5%). On univariate analysis, predictors
      of remediation included receiving honors in the third-year surgery clerkship,
      United States Medical Licensing Examination (USMLE) step 1 and/or step 2, and
      American Board of Surgery In-Training Examination scores at postgraduate years 1
      through 4. On multivariable regression analysis, remediation was associated with
      receiving honors in surgery (odds ratio, 1.9; P = .01) and USMLE step 1 score
      (odds ratio, 0.9; P = .02). On univariate analysis, the only predictor of
      attrition was the American Board of Surgery In-Training Examination score at the
      postgraduate year 3 level (P = .04). CONCLUSIONS: Almost one third of categorical
      general surgery residents required remediation during residency, which was most
      often owing to medical knowledge deficits. Lower USMLE step 1 scores were
      predictors of the need for remediation. Most remediated residents successfully
      completed the program. Given the high rates of remediation and the increased
      educational burden on clinical faculty, medical schools need to focus on better
      preparing students to enter surgical residency.

PMID- 22987174
TI  - Remediation and attrition: are they related? Comment on "general surgery resident
      remediation and attrition".

PMID- 22987175
TI  - Selective preoperative magnetic resonance imaging in women with breast cancer: no
      reduction in the reoperation rate.
AB  - HYPOTHESIS: The use of preoperative magnetic resonance (MR) imaging may have an
      effect on the reoperation rate in women with operable breast cancer. DESIGN:
      Retrospective cohort study. SETTING: University medical center. PATIENTS: Women
      with operable breast cancer treated by a single surgeon between January 1, 2006,
      and December 31, 2010. INTERVENTION: Selective preoperative MR imaging based on
      breast density and histologic findings. MAIN OUTCOME MEASURES: Reoperation rate
      and pathologically avoidable mastectomy at initial operation. RESULTS: Of 313
      patients in the study, 120 underwent preoperative MR imaging. Patients undergoing
      MR imaging were younger (mean age, 53.6 vs 59.5 years; P < .001), were more often
      of non-Hispanic white race/ethnicity (61.7% vs 52.3%, P < .05), and more likely
      had heterogeneously dense or very dense breasts (68.4% vs 22.3%, P < .001). The
      incidence of lobular carcinoma (8.3% in the MR imaging group vs 5.2% in the no MR
      imaging group, P = .27) and the type of surgery performed (mastectomy vs partial
      mastectomy, P = .67) were similar in both groups. The mean pathological size of
      the index tumor in the MR imaging group was larger than that in the no MR imaging
      group (2.02 vs 1.72 cm, P = .009), but the extent of disease was comparable
      (75.8% in the MR imaging group vs 82.9% in the no MR imaging group had
      pathologically localized disease, P = .26). The reoperation rate was similar
      between the 2 groups (19.1% in the MR imaging group vs 17.6% in the no MR imaging
      group, P = .91) even when stratified by breast density (P = .76), pT2 tumor size
      (P = .35), or lobular carcinoma histologic findings (P = .26). Pathologically
      avoidable mastectomy (multifocal or multicentric MR imaging and unifocal
      histopathological findings) was observed in 12 of 47 patients (25.5%) with
      preoperative MR imaging who underwent mastectomy. CONCLUSION: The selective use
      of preoperative MR imaging to decrease reoperation in women with breast cancer is
      not supported by these data. In a considerable number of patients, MR imaging
      overestimates the extent of disease.

PMID- 22987176
TI  - Preoperative breast magnetic resonance imaging: a solution looking for a problem:
      comment on "selective preoperative magnetic resonance imaging in women with
      breast cancer"a solution looking for a problem.

PMID- 22987177
TI  - Outcomes of open operation for aortoiliac occlusive disease after failed
      endovascular therapy.
AB  - OBJECTIVES: To compare patient outcomes of primary open operation for aortoiliac
      occlusive disease (AIOD) with those of secondary open operations for failed
      endovascular therapy (ET) of AIOD. DESIGN: A retrospective cohort study was
      performed analyzing demographic characteristics, comorbidities, and outcomes.
      SETTING: Affiliated Veterans Affairs Hospital from January 1, 1998, through March
      31, 2010. PATIENTS: Patients who underwent primary open operation for AIOD or
      secondary open operation for failed ET of AIOD. MAIN OUTCOME MEASURES: Overall
      survival and limb salvage. RESULTS: Primary open operations (n = 153) were 67
      aortobifemoral grafts (43.8%), 38 axillobifemoral grafts (24.8%), and 48 femoral
      femoral grafts (31.4%). Secondary open operations (n = 35) were 28 aortobifemoral
      grafts (80.0%), 5 axillobifemoral grafts (14.3%), and 2 femoral-femoral grafts
      (5.7%). Mean (SD) 5-year survival was 48.2% (5.6%) and 66.8% (10.0%),
      respectively, for patients undergoing primary vs secondary open surgery for AIOD
      (P = .01). There were 7 amputations during a mean follow-up of 3 years, all in
      the primary open surgery group. CONCLUSIONS: Despite a higher proportion of
      coronary artery disease and a 20% conversion of claudication to critical limb
      ischemia after failed ET for AIOD, survival was longer in patients undergoing
      secondary vs primary open surgery. Patients who underwent open surgery after
      failed ET for AIOD did not require amputation. Failed ET for AIOD does not lead
      to worse outcomes for patients undergoing open surgery for AIOD.

PMID- 22987178
TI  - Could the endo-first strategy really be better?

PMID- 22987179
TI  - Analysis of obesity-related outcomes and bariatric failure rates with the
      duodenal switch vs gastric bypass for morbid obesity.
AB  - OBJECTIVE: To compare the outcomes of a large cohort undergoing biliopancreatic
      diversion/duodenal switch (DS) vs gastric bypass (GB). DESIGN: Retrospective
      review of the Bariatric Outcomes Longitudinal Database from 2007 to 2010. All
      inpatient and outpatient follow-up data were analyzed. SETTING: Multicenter
      database. PATIENTS: Patients undergoing primary DS were compared with a
      concurrent cohort undergoing GB. MAIN OUTCOME MEASURES: The main outcome measures
      were (1) weight loss; (2) control of comorbidities including diabetes mellitus,
      hypertension, and sleep apnea; and (3) failure to achieve at least 50% excess
      body weight loss. RESULTS: One thousand five hundred forty-five patients
      underwent DS and 77 406 underwent GB, with a mean preoperative body mass index
      (BMI; calculated as weight in kilograms divided by height in meters squared) of
      52 and 48, respectively (P < .01). The DS was associated with longer operative
      times, greater blood loss, and longer lengths of hospital stay (all P < .05).
      Early reoperation rates were higher in the DS group (3.3% vs 1.5%). Percentage of
      change in BMI was significantly greater in the DS group at all follow-up
      intervals (P < .05). Subgroup analysis of the superobese population (BMI >50)
      revealed significantly greater percentage of excess body weight loss in the DS
      group at 2 years (79% vs 67%; P < .01). Comorbidity control of diabetes,
      hypertension, and sleep apnea were all superior with the DS (all P < .05). The
      risk of weight loss failure was significantly reduced with DS vs GB for all
      patients, with a greater reduction in the BMI more than 50 subgroup. CONCLUSIONS:
      The DS is a less commonly used bariatric operation, with higher early risks
      compared with GB. However, the DS achieved better weight and comorbidity control,
      with even more pronounced benefits among the superobese.

PMID- 22987180
TI  - Gastric bypass: time for a change?

PMID- 22987181
TI  - Influence of resident involvement on trauma care outcomes.
AB  - HYPOTHESIS: Discrepancies exist in complications and outcomes at teaching trauma
      centers (TTCs) vs nonteaching TCs (NTCs). DESIGN: Retrospective review of the
      National Trauma Data Bank research data sets (January 1, 2007, through December
      31, 2008). SETTING: Level II TCs. PATIENTS: Patients at TTCs were compared with
      patients at NTCs using demographic, clinical, and outcome data. Regression
      modeling was used to adjust for confounding factors to determine the effect of
      house staff presence on failure to rescue, defined as mortality after an in-house
      complication. MAIN OUTCOME MEASURES: The primary outcome measures were major
      complications, in-hospital mortality, and failure to rescue. RESULTS: In total,
      162 687 patients were available for analysis, 36 713 of whom (22.6%) were
      admitted to NTCs. Compared with patients admitted to TTCs, patients admitted to
      NTCs were older (52.8 vs 50.7 years), had more severe head injuries (8.3% vs
      7.8%), and were more likely to undergo immediate operation (15.0% vs 13.2%) or
      ICU admission (28.1% vs 22.8%) (P < .01 for all). The mean Injury Severity Scores
      were similar between the groups (10.1 for patients admitted to NTCs vs 10.4 for
      patients admitted to TTCs, P < .01). Compared with patients admitted to TTCs,
      patients admitted to NTCs experienced fewer complications (adjusted odds ratio
      [aOR], 0.63; P < .01), had a lower adjusted mortality rate (aOR, 0.87; P = .01),
      and were less likely to experience failure to rescue (aOR, 0.81; P = .01).
      CONCLUSIONS: Admission to level II TTCs is associated with an increased risk for
      major complications and a higher rate of failure to rescue compared with
      admission to level II NTCs. Further investigation of the differences in care
      provided by level II TTCs vs NTCs may identify areas for improvement in residency
      training and processes of care.

PMID- 22987182
TI  - Failure to rescue from residents?

PMID- 22987183
TI  - Umbilical hernia repair in patients with signs of portal hypertension: surgical
      outcome and predictors of mortality.
AB  - OBJECTIVES: To compare the outcomes of umbilical hernia repair in patients with
      and without signs of portal hypertension, such as esophageal varices or ascites;
      to assess the effect of emergency surgery on complication rates; and to identify
      predictors of postoperative mortality. DESIGN: Database search from January 1,
      2005, through December 31, 2009. SETTING: North American hospitals participating
      in the American College of Surgeons National Surgical Quality Improvement Program
      initiative. PATIENTS: We studied patients who underwent umbilical hernia repair.
      Those with congestive heart failure, disseminated malignant tumor, or chronic
      renal failure while undergoing dialysis were excluded. MAIN OUTCOME MEASURES:
      Preoperative variables and perioperative course were analyzed. Main outcome
      measures were morbidity and mortality after umbilical hernia repair. RESULTS: A
      total of 390 patients with ascites and/or esophageal varices formed the study
      group, and the remaining 22 952 patients formed the control group. The overall
      morbidity and mortality rates for the study group were 13.1% and 5.1%, whereas
      these rates were 3.9% and 0.1% for the control group, respectively (P < .001).
      For the study group, the mortality after elective repair among patients with a
      model for end-stage liver disease (MELD) score greater than 15 was 11.1% compared
      with 1.3% in patients with a MELD score of 15 or less. The patients with ascites
      and/or esophageal varices underwent emergency surgery more frequently than the
      control group (37.7% vs 4.9%; P < .001). Emergency surgery for the study group
      was associated with a higher morbidity than elective surgery (20.8% vs 8.3%; P <
      .001) but not a significantly higher mortality (7.4% vs 3.7%; P = .11). However,
      logistic regression analysis showed that age older than 65 years, MELD score
      higher than 15, albumin level less than 3.0 g/dL (to convert to grams per liter,
      multiply by 10), and sepsis at presentation were more predictive of postoperative
      mortality. CONCLUSIONS: Umbilical hernia repair in the presence of ascites and/or
      esophageal varices is associated with significant postoperative complication
      rates. Emergency surgery is associated with higher morbidity rates but not
      significantly higher mortality rates. Elective repair of umbilical hernia should
      be avoided for those with adverse predictors, such as age older than 65 years,
      MELD score higher than 15, and albumin level less than 3.0 g/dL.

PMID- 22987184
TI  - Should a patient with cirrhosis have an innie or an outie?

PMID- 22987186
TI  - Is palpation in the operating room the best method for surgical planning?

PMID- 22987185
TI  - Preoperative imaging of pulmonary metastases in patients with melanoma:
      implications for minimally invasive techniques.
AB  - HYPOTHESIS: Preoperative imaging underestimates the number of pulmonary melanoma
      metastases. Although thoracoscopic resection is less invasive than resection via
      thoracotomy, it does not allow manual palpation of the lung to identify any
      metastases not visible on the preoperative scan or at the time of resection.
      DESIGN: Retrospective review of a prospectively maintained database. SETTING:
      Tertiary referral center. PATIENTS: A total of 170 patients who underwent
      preoperative computed tomography of the chest, followed within 30 days by
      thoracotomy for resection of pulmonary metastatic melanoma. MAIN OUTCOME
      MEASURES: Number of pathology-confirmed pulmonary metastases detected by
      preoperative chest computed tomography vs intraoperative manual palpation.
      RESULTS: The mean age of the patients was 49.5 years at initial diagnosis of
      melanoma and 57.1 years at diagnosis of pulmonary metastases; 69% of patients
      were male. A total of 334 pulmonary metastases were resected; the mean lesion
      size was 2.0 cm (range, 0.1-14.0 cm). In 49 of 190 pulmonary resections (26%),
      manual palpation of the subpleural parenchyma revealed lesions not identified
      during preoperative imaging. The rate of 5-year overall survival was 33%.
      CONCLUSIONS: Preoperative imaging underestimates the number of pulmonary lesions
      in patients with metastatic melanoma. Because incomplete resection of metastatic
      disease is associated with worse outcomes, we recommend caution when considering
      a minimally invasive approach for the resection of pulmonary metastatic melanoma.

PMID- 22987187
TI  - Detection of colon cancer metastases with fluorescence laparoscopy in orthotopic
      nude mouse models.
AB  - OBJECTIVE: To improve detection of colon cancer metastases using fluorescence
      laparoscopy (FL). DESIGN: An orthotopic mouse model of human colon cancer was
      established by intracecal injection of HCT-116 human colon cancer cells
      expressing green fluorescent protein into 12 mice. One group modeled early
      disease and the second modeled late metastatic disease. For the early-disease
      model, 2 weeks after implantation, 6 mice underwent 2 modalities of laparoscopy:
      bright field laparoscopy (BL) and FL. The number of metastases identified within
      each of the 4 abdominal quadrants was recorded with both laparoscopy modalities.
      This process was repeated in the late-metastatic disease group 4 weeks after
      implantation. All animals were then humanely sacrificed and imaged using open
      fluorescence laparoscopy (OL) as a positive control to identify metastases.
      SETTING: Basic science laboratory. PARTICIPANTS: Twelve female, 6-week-old nude
      mice. INTERVENTIONS: Detection of tumor foci by FL compared with BL. MAIN OUTCOME
      MEASURES: Number of tumors identified in each quadrant. RESULTS Fluorescence
      laparoscopy enabled superior visualization of colon cancer metastases compared
      with BL in the early (P = .03) and late (P = .002) models of colon cancer.
      Compared with OL, BL was significantly inferior in the early (P = .04) and late
      (P < .001) groups. Fluorescence laparoscopy was not significantly different from
      OL in the early (P = .85) or late (P = .46) group. Thus, FL allowed
      identification of micrometastases that could not be distinguished from
      surrounding tissue using BL. CONCLUSIONS: The use of FL enables identification of
      metastases that could not be visualized using standard laparoscopy. This report
      illustrates the important clinical potential for FL in the surgical treatment of
      cancer.

PMID- 22987188
TI  - Appropriate surgical procedure for dominant thyroid nodules of the isthmus 1 cm
      or larger.
AB  - HYPOTHESIS: Surgeon-performed ultrasound (SUS) and fine-needle aspiration (FNA)
      may guide the management of dominant thyroid nodules of the isthmus. DESIGN:
      Retrospective review of prospectively collected data. SETTING: Tertiary academic
      referral center. PATIENTS: Of 942 patients who underwent preoperative SUS and
      FNA, followed by thyroidectomy, between January 1, 2002, and April 10, 2010, a
      total of 28 patients had a dominant thyroid nodule of the isthmus. MAIN OUTCOME
      MEASURES: Preoperative SUS features and FNA findings and final pathologic
      results. RESULTS: Of 28 patients (3%) who had a dominant thyroid nodule of the
      isthmus, 16 had benign final pathologic results, with all having at least 2
      benign SUS features and 9 having 3 benign SUS features; 15 of 16 patients had an
      FNA finding that was benign or indeterminate. Of 12 patients with malignant final
      pathologic results, 8 had 3 malignant SUS features, and all had an FNA finding
      that was malignant or suspicious for a malignant neoplasm. Among these 12
      patients, final pathologic results demonstrated multifocal disease (8 patients),
      extracapsular invasion (4 patients), or lymph node involvement (7 patients). When
      11 patients with a malignant dominant thyroid nodule of the isthmus were compared
      with an overall group of 270 other well-differentiated papillary thyroid
      carcinomas 1 cm or larger on final pathologic results, patients with isthmus
      nodules trended toward having higher rates of multifocal disease (P = .08),
      extracapsular invasion (P = .09), and lymph node involvement (P = .09).
      CONCLUSIONS: Preoperative SUS features and FNA findings in patients with dominant
      thyroid nodules of the isthmus can accurately predict malignant or benign thyroid
      disease and direct the extent of thyroidectomy. For malignant isthmus nodules,
      total thyroidectomy and possible central node dissection are recommended owing to
      high rates of multifocal disease and lymph node involvement. For benign isthmus
      nodules, thyroid lobectomy with isthmusectomy or isthmusectomy alone may be
      appropriate.

PMID- 22987189
TI  - Image of the month-quiz case. Diagnosis: primary colorectal carcinoma with
      ovarian metastasis.

PMID- 22987191
TI  - Image of the month-quiz case. Diagnosis: primary adenocarcinoma.

PMID- 22987193
TI  - Benchmarking curriculum content in entry-level health professional education with
      special reference to health promotion practice in physical therapy: a multi
      institutional international study.
AB  - Health promotion (HP) warrants being a clinical competency for health
      professionals given the global burden of lifestyle-related conditions; these are
      largely preventable with lifestyle behavior change. Physical therapists have a
      practice pattern conducive to HP, including lifestyle behavior change. The extent
      to which HP content is included in entry-level physical therapy (PT) curricula,
      and how it is taught however, is unknown. The aim of this study was to benchmark
      lifestyle behavior HP content within entry-level curricula of international PT
      programs. The sampling frame included 258 accredited PT academic programs
      spanning six countries. An internet-based survey was used to assess HP curricular
      content. Descriptive questions for HP topics (smoking cessation, nutrition,
      weight control, alcohol consumption, exercise, and stress management) included
      hours allotted and instructional methods used. Chi square tests examined
      differences between the proportion of programs in the United States (US) and
      other countries (combined) for HP topics, and among HP topics regarding
      instructional methods. The response rate was 48 %. Most programs (>80 %) included
      all HP topics except alcohol consumption (65.5 % of programs). Instructional
      methods used were primarily theory-based; few programs (range 2.6-24.1 %)
      combined theory, practical and attainment of clinical competency for all HP
      topics (exercise prescription notwithstanding). Proportionally, more US programs
      included alcohol and nutrition than other countries combined. Overall, HP
      lifestyle behavior topics were included to varying extent; however, instructional
      methods used and hours allotted per topic varied across PT curricula. Universal
      standards of HP practice as a clinical competency are warranted within the
      profession.

PMID- 22987194
TI  - Outcome (competency) based education: an exploration of its origins, theoretical
      basis, and empirical evidence.
AB  - Outcome based or competency based education (OBE) is so firmly established in
      undergraduate medical education that it might not seem necessary to ask why it
      was included in recommendations for the future, like the Flexner centenary
      report. Uncritical acceptance may not, however, deliver its greatest benefits.
      Our aim was to explore the underpinnings of OBE: its historical origins,
      theoretical basis, and empirical evidence of its effects in order to answer the
      question: How can predetermined learning outcomes influence undergraduate medical
      education? This literature review had three components: A review of historical
      landmarks in the evolution of OBE; a review of conceptual frameworks and
      theories; and a systematic review of empirical publications from 1999 to 2010
      that reported data concerning the effects of learning outcomes on undergraduate
      medical education. OBE had its origins in behaviourist theories of learning. It
      is tightly linked to the assessment and regulation of proficiency, but less
      clearly linked to teaching and learning activities. Over time, there have been
      cycles of advocacy for, then criticism of, OBE. A recurring critique concerns the
      place of complex personal and professional attributes as "competencies". OBE has
      been adopted by consensus in the face of weak empirical evidence. OBE, which has
      been advocated for over 50 years, can contribute usefully to defining requisite
      knowledge and skills, and blueprinting assessments. Its applicability to more
      complex aspects of clinical performance is not clear. OBE, we conclude, provides
      a valuable approach to some, but not all, important aspects of undergraduate
      medical education. 

PMID- 22987195
TI  - A new class of soluble and stable transition-metal-substituted polyoxoniobate:
      [Cr2(OH)4Nb10O30]8-.
AB  - Hydrothermal synthesis of [Cr(III)(2)(OH)(4)Nb(10)O(30)](8-) in gram-scale
      quantities leads to a new polyoxometalate ion composed of two CrNb(6)O(19)
      Lindqvist-type units that are fused via shared faces. The two Cr(III) atoms are
      located in the centre of the molecule and are bridged by two MU(4)-O atoms.
      Electronic transitions are calculated using density functional theory and compare
      well with the measured UV-Vis spectra.

PMID- 22987196
TI  - Alterations of fibrin network structure mediated by dermatan sulfate.
AB  - Dermatan sulfate (DS) is well-known for its anticoagulant activity through
      binding to heparin cofactor II (HCII) to enhance thrombin inhibition. It has also
      been reported that DS has a profibrinolytic effect. We have evaluated the effects
      of DS solutions (4-20 MUg/mL) on the formation (by kinetic studies), structure
      (by electron microscopy and compaction assays) and lysis (with urokinase-type
      plasminogen activator) of plasma fibrin networks. The results showed that DS
      significantly prolonged the lag phase and decreased the fibrin formation rate and
      the optical density of the final networks versus control, in a concentration
      dependent way. DS-associated networks presented a minor network percentage
      compared with control, composed of lower number of fibers per field, which
      resulted significantly thinner and longer. Moreover, DS rendered gels more
      sensible to rupture by centrifugal force and more susceptible to lysis. When
      fibrin formation kinetic assays were performed with purified fibrinogen instead
      of plasma, in the absence of HCII, the optical density of final DS-associated
      networks was statistically lower than control. Therefore, a direct effect of DS
      on the thickness of fibers was observed. Since in all in vitro assays low DS
      concentrations were used, it could be postulated that the fibrin features
      described above are plausible to be found in in vivo thrombi and therefore, DS
      would contribute to the formation of less thrombogenic clots.

PMID- 22987197
TI  - Increased risk of minor bleeding and antiplatelet therapy cessation in patients
      with acute coronary syndromes and low on-aspirin platelet reactivity. A
      prospective cohort study.
AB  - Bleeding negatively affects prognosis and adherence to antiplatelet therapy after
      acute coronary syndromes (ACSs). The potential association of on-aspirin platelet
      reactivity and bleeding is not established. We sought to determine whether low on
      aspirin platelet reactivity (LAPR) is associated with bleeding events and
      antiplatelet therapy compliance in patients with ACSs receiving coronary
      stenting. On-aspirin platelet reactivity was measured by the VerifyNowTM Aspirin
      assay (Accumetrics Inc., San Diego, CA, USA) in 531 patients with ACS. Cut-offs
      for LAPR were calculated by receiver-operating characteristic curve (ROC)
      analysis. Bleeding was reported according to Bleeding Academic Research
      Consortium (BARC) definition. The endpoints were minor bleeding (BARC types 1 or
      2), major bleeding (BARC types 3 or 5) and antiplatelet therapy cessation during
      6-months follow-up. By ROC analysis the VerifyNowTM Aspirin assay was able to
      distinguish between patients with and without minor bleeding (area under the
      curve [AUC] 0.66, 95 % confidence interval [CI] 0.62-0.70, P < 0.0001) whereas
      major bleeding could not be predicted by the assay (AUC 0.54, 95 % CI 0.49-0.58,
      P = 0.473). By logistic regression, LAPR was associated with increased risk of
      minor bleeding (odds ratio [OR] 4.32, 95 % CI 2.78-6.71, P < 0.0001) but not
      major bleeding (OR 2.05, 95 % CI 0.83-5.06, P = 0.117). Antiplatelet therapy
      discontinuation was more frequent in patients with LAPR as compared to those with
      no LAPR (21.6 vs. 9.1 %, P = 0.0008). In conclusion, early point-of-care on
      aspirin platelet reactivity testing in ACS may identify patients with increased
      risk of minor bleeding events and subsequent discontinuation of antiplatelet
      therapy. The possible impact of LAPR on major bleeding needs to be determined in
      larger trials.

PMID- 22987198
TI  - Mouse islet of Langerhans isolation using a combination of purified collagenase
      and neutral protease.
AB  - The interrogation of beta cell gene expression and function in vitro has squarely
      shifted over the years from the study of rodent tumorigenic cell lines to the
      study of isolated rodent islets. Primary islets offer the distinct advantage that
      they more faithfully reflect the biology of intracellular signaling pathways and
      secretory responses. Whereas the method of islet isolation using tissue
      dissociating enzyme (TDE) preparations has been well established in many
      laboratories(1-4), variations in the consistency of islet yield and quality from
      any given rodent strain limit the extent and feasibility of primary islet
      studies. These variations often occur as a result of the crude partially purified
      TDEs used in the islet isolation procedure; TDEs frequently exhibit lot-to-lot
      variations in activity and often require adjustments to the dose of enzyme used.
      A small number of reports have used purified TDEs for rodent cell isolations(5,
      6), but the practice is not widespread despite the routine use and advantages of
      purified TDEs for human islet isolations. In collaboration with VitaCyte, LLC
      (Indianapolis, IN), we developed a modified mouse islet isolation protocol based
      on that described by Gotoh(7, 8), in which the TDEs are perfused directly into
      the pancreatic duct of mice, followed by crude tissue fractionation through a
      Histopaque gradient(9), and isolation of purified islets. A significant
      difference in our protocol is the use of purified collagenase (CIzyme MA) and
      neutral protease (CIzyme BP) combination. The collagenase was characterized by
      the use of a(6) fluorescence collagen degrading activity (CDA) assay that
      utilized fluorescently labeled soluble calf skin fibrils as substrate(6). This
      substrate is more predictive of the kinetics of collagen degradation in the
      tissue matrix because it relies on native collagen as the substrate. The protease
      was characterized with a sensitive fluorescent kinetic assay(10). Utilizing these
      improved assays along with more traditional biochemical analysis enable the TDE
      to be manufactured more consistently, leading to improved performance consistency
      between lots. The protocol described in here was optimized for maximal islet
      yield and optimal islet morphology using C57BL/6 mice. During the development of
      this protocol, several combinations of collagenase and neutral proteases were
      evaluated at different concentrations, and the final ratio of collagenase:neutral
      protease of 35:10 represents enzyme performance comparable to Sigma Type XI.
      Because significant variability in average islet yields from different strains of
      rats and mice have been reported, additional modifications of the TDE composition
      should be made to improve the yield and quality of islets recovered from
      different species and strains.

PMID- 22987200
TI  - Enhanced enantioselectivity of a carboxyl esterase from Rhodobacter sphaeroides
      by directed evolution.
AB  - The present work created an esterase variant from Rhodobacter sphaeroides (RspE)
      with enhanced selectivity in hydrolytic kinetic resolutions by directed
      evolution. A "model" substrate, methyl mandelate, was introduced in the high
      throughput screening procedure. E values of a variant CH (Asn62Cys/Leu145His) for
      six different esters were 10-83, which were a relative improvement compared to 2
      20 for the wild type. Our subsequent crystal structure interpretation and
      molecular dynamics simulations helped shed light on the source of
      enantioselectivity modified by directed evolution. Though mutations displayed no
      "direct" interaction with the substrate, they were hypothesized to strengthen the
      intramolecular interaction in the catalytic cavity of variant. Conformation
      analysis revealed that the enhanced enantioselectivity of variant CH for the
      seven substrates applied in this study was derived from the decrease in size of
      the substrate binding pocket.

PMID- 22987199
TI  - Asymmetric reduction of diketones by two Gluconobacter oxydans oxidoreductases.
AB  - Two genes encoding recombinant cytosolic oxidoreductases from Gluconobacter
      oxydans, gox0313 and gox0646, were heterologously expressed in Escherichia coli
      and the resulting proteins were purified and characterized. GOX0313 was
      identified as a medium-chain alcohol dehydrogenase, whereas GOX0646 was
      classified as a ketocarbonyl reductase. GOX0313 had a broad substrate spectrum
      and oxidized various primary alcohols. However, GOX0313 had a preference for
      substrate reduction, reducing many aldehydes and alpha-diketones. In contrast,
      GOX0646 had a narrow substrate spectrum and reduced alpha-diketones, preferring
      short-chain ketocarbonyls. Both enzymes regio- and stereospecifically reduced
      alpha-diketones to the corresponding (S)-hydroxy ketone, as shown by NMR. These
      products are difficult to produce chemically, requiring complicated protecting
      group chemistry. Furthermore, hydroxy ketones find industrial application in the
      production of pheromones, fragrances, flavors, and pharmaceuticals. Hence, these
      enzymes are interesting biocatalysts for the production of enantiomerically pure
      building blocks that are difficult to prepare chemically.

PMID- 22987201
TI  - Production of sophorolipids with enhanced volumetric productivity by means of
      high cell density fermentation.
AB  - To achieve high time-space efficiency for sophorolipid production with yeast
      Candida bombicola, a strategy of high cell density fermentation was employed. The
      approach consisted of two sequential stages: (1) the optimization of the carbon
      source and the nutrient concentration to achieve the maximal cell density and (2)
      the computer-aided adjustment of physical parameters and the controlled feeding
      of substrates for enhanced volumetric productivity. Both stages have been
      successfully implemented in a 10-L fermenter, where up to 80 g dry cell weight/L
      was obtained and a remarkably high volumetric productivity (> 200 g isolated
      sophorolipids/L/day) was achieved. Both the biomass and volumetric productivity
      were markedly higher than previously reported. Specifically, the high
      productivity of sophorolipids could be attained on a very short time scale (24
      h), highlighting the industrial potential of the platform developed in this work.

PMID- 22987202
TI  - Autodisplay of nitrilase from Klebsiella pneumoniae and whole-cell degradation of
      oxynil herbicides and related compounds.
AB  - Using the Autodisplay system, a recombinant Escherichia coli strain displaying
      the dimeric nitrilase from Klebsiella pneumoniae subsp. ozaenae (NitKp) on the
      cell surface was constructed. Localization of the nitrilase in the cell envelope
      of E. coli was monitored by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and surface exposure was verified by its accessibility to
      externally added protease. The whole-cell biocatalyst obtained converted the
      substrates analyzed in the following order: chloroxynil > bromoxynil > ioxynil >
      3-bromo-4-hydroxybenzonitrile (1.67, 0.89, 0.13, and 0.09 mM product formation
      within 72 h, respectively), indicating the same substrate specificity for the
      displayed enzyme as for the free enzyme. The whole-cell biocatalyst was also able
      to convert 3-fluoro-4-hydroxybenzonitrile and 3,5-dimethyl-4-hydroxybenzonitrile
      to the corresponding carboxylic acids. In contrast, it was not possible to detect
      any enzyme activity when 4-methoxybenzonitrile was used as substrate. The
      temperature optimum determined was 45  degrees C for the surface-displayed enzyme
      instead of 35  degrees C for the purified enzyme. In addition, the optimum
      activity of the displayed nitrilase was shifted to more acidic pH in comparison
      to the free enzyme.

PMID- 22987203
TI  - Reconciling social interaction with habitat selection in territorial species.
AB  - The concept of habitat selection as the primary force in clustered distributions
      has been challenged by behavioral studies of conspecific attraction. This has
      lead to two conflicting explanations for settlement behavior, which we have
      integrated into one model. This model creates a range of fitness outcomes for
      different settlement strategies, encompassing the four combinations of positive
      and negative effects of the habitat selection and social interaction. It expands
      the ideal free distribution models (negative intra-specific interactions and
      positive habitat selection), to consider alternative situations where (1)
      beneficial social interaction increases fitness for clustered pairs in poor
      quality habitat, (2) neither habitat selection nor conspecific attraction can
      improve fitness, and (3) where both are beneficial and do not interfere with each
      other. The model does this by establishing an intrinsic fitness, where the
      effects of both habitat selection (h) and conspecific attractions (c) are neutral
      (h=c=1) and do not influence settlement. Clustered distributions occur when h.c>1
      because the fitness in clusters is greater than intrinsic fitness. Dispersed
      distributions occur when h.c<1 and fitness is lower than the intrinsic. The
      benefit of the model is that it allows conspecific attraction to be considered a
      positive force in fitness without rejecting the proven concept of ideal free
      distribution.

PMID- 22987204
TI  - Impact of the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act
      on abdominal ultrasonography use among Medicare beneficiaries.
AB  - BACKGROUND: Since January 1, 2007, Medicare has covered abdominal aortic aneurysm
      (AAA) screening for new male enrollees with a history of smoking under the
      Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act. We examined
      the association between this program and abdominal ultrasonography for AAA
      screening, elective AAA repair, hospitalization for AAA rupture, and all-cause
      mortality. METHODS: We used a 20% sample of traditional Medicare enrollees from
      2004 to 2008 to identify 65-year-old men eligible for screening and 3 control
      groups not eligible for screening (70-year-old men, 76-year-old men, and 65-year
      old women). We used logistic regression to examine the change in outcomes at 365
      days for eligible vs ineligible beneficiaries before and after SAAAVE Act
      implementation, adjusting for comorbidities, state-level smoking prevalence,
      geographic variation, and time trends. RESULTS: Fewer than 3% of abdominal
      ultrasonography claims after 2007 were for SAAAVE-specific AAA screening. There
      was a significantly greater increase in abdominal ultrasonography use among
      SAAAVE-eligible beneficiaries (2.0 percentage points among 65-year-old men, from
      7.6% in 2004 to 9.6% in 2008; 0.7 points [8.9% to 9.6%] among 70-year-old men;
      0.7 points [10.8% to 11.5%] among 76-year-old men; and 0.9 points [7.5% to 8.4%]
      among 65-year-old women) (P < .001 for all comparisons with 65-year-old men). The
      SAAAVE Act was associated with increased use of abdominal ultrasonography in 65
      year-old men compared with 70-year-old men (adjusted odds ratio [AOR], 1.15; 95%
      CI, 1.11-1.19) (P < .001), and this increased use remained even when SAAAVE
      specific AAA screening was excluded (AOR, 1.12; 95% CI, 1.08-1.16) (P < .001).
      Implementation of the SAAAVE Act was not associated with changes in rates of AAA
      repair, AAA rupture, or all-cause mortality. CONCLUSIONS: The impact of the
      SAAAVE Act on AAA screening was modest and was based on abdominal ultrasonography
      use that it did not directly reimburse. The SAAAVE Act had no discernable effect
      on AAA rupture or all-cause morality.

PMID- 22987205
TI  - Somatic mosaicism and double somatic hits can lead to MSI colorectal tumors.
AB  - Some patients happen to have a colorectal cancer with microsatellite instability
      (MSI), but without any alteration in Mismatch Repair (MMR) system (germline
      mutation/promoter methylation). We aimed to identify the mechanism of
      inactivation of MMR genes in those cases. We studied 18 patients with MSI CCR and
      loss of expression of a MMR protein. DNA was extracted from tumoral and normal
      colonic material. We studied the 3 main MMR genes in tumors, by sequencing and
      large rearrangement analysis, and looked for mosaicism. Seven patients lost
      expression of MLH1, we found 1 mutation in the tumor for 3 patients and 2
      mutations in one. Eight patients lost expression of MSH2: we found 1 mutation in
      2 patients and 2 mutations in four. In the 5 cases with 2 hits, MSI was due to
      double somatic hits (n = 3), mosaicism (n = 1) and missed germline mutation (n =
      1). Mosaicism was confirmed by HRM analysis, and by finding a germline mutation
      in one patient's son. We could explain MSI in the tumors of 5 patients (27.8 %).
      Their follow up and family's surveillance could be adjusted, as the sporadic
      cases don't require intensive surveillance. We describe the first case of somatic
      mosaicism after de novo mutation in MSH2.

PMID- 22987207
TI  - Reply: To PMID 22290640.

PMID- 22987208
TI  - Investing in children: changes in parental spending on children, 1972-2007.
AB  - Parental spending on children is often presumed to be one of the main ways that
      parents invest in children and a main reason why children from wealthier
      households are advantaged. Yet, although research has tracked changes in the
      other main form of parental investment-namely, time-there is little research on
      spending. We use data from the Consumer Expenditure Survey to examine how
      spending changed from the early 1970s to the late 2000s, focusing particularly on
      inequality in parental investment in children. Parental spending increased, as
      did inequality of investment. We also investigate shifts in the composition of
      spending and linkages to children's characteristics. Investment in male and
      female children changed substantially: households with only female children spent
      significantly less than parents in households with only male children in the
      early 1970s; but by the 1990s, spending had equalized; and by the late 2000s,
      girls appeared to enjoy an advantage. Finally, the shape of parental investment
      over the course of children's lives changed. Prior to the 1990s, parents spent
      most on children in their teen years. After the 1990s, however, spending was
      greatest when children were under the age of 6 and in their mid-20s.

PMID- 22987206
TI  - Novel mutations of the APC gene and genetic consequences of splicing mutations in
      the Czech FAP families.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with
      almost 100 % risk of colorectal cancer. The typical FAP is characterized by
      hundreds to thousands of colorectal adenomatous polyps and by extracolonic
      manifestations, later onset and lower number of polyps in colon is characteristic
      of an attenuated form (AFAP). We analyzed the APC gene for germline mutations in
      90 FAP/AFAP patients. Mutation screening was performed using Denaturing Gradient
      Gel Electrophoresis. DNA fragments showing an aberrant electrophoretic banding
      pattern were sequenced. APC-mutation-negative probands were screened for large
      deletions of the APC gene using multiplex ligation dependent probe amplification.
      Analysis of mRNA variants followed in probands with possible splicing mutation by
      PCR amplification of target site flanking exons and sequencing the normal and
      aberrant products. We identified 30 germline variants among 36 unrelated probands
      including large deletions. Eleven APC variants detected last two years have not
      been reported yet. At all, fifteen of them are expected to cause errors in mRNA
      splicing. Analysis of mRNA in ten of these patients revealed exon skipping in
      seven cases, exonisation of intron in one of these as well, change of the amount
      of alternatively spliced product in one case, and no effect was found in three
      cases. In two of the patients, the biopsy of colon mucosa and polyp enabled us to
      examine the effect of the mutation on splicing pattern in colon cells directly.
      The comparison of alternative and standard transcript amount showed similar
      transcription pattern of exon 14 in control colon mucosa tissue (9 samples) as in
      51 blood control samples.

PMID- 22987209
TI  - Plantar pressures and relative lesser metatarsal lengths in older people with and
      without forefoot pain.
AB  - Forefoot pain is a common problem in older people. We determined whether plantar
      pressures during gait and the relative lengths of the lesser metatarsals differ
      between older people with and without plantar forefoot pain. Dynamic plantar
      pressure assessment during walking was undertaken using the Tekscan MatScan(r)
      system in 118 community-dwelling older people (44 males and 74 females), mean age
      74 (standard deviation=5.9) years, 43 (36%) of whom reported current or previous
      plantar forefoot pain. The relative lengths of metatarsals 1-5 were determined
      from weightbearing X-rays. Participants with current or previous plantar forefoot
      pain exhibited significantly (p=0.032) greater peak plantar pressure under
      metatarsal heads 3-5 (1.93 +/- 0.41 kg/cm(2) vs. 1.74 +/- 0.48 kg/cm(2) ).
      However, no differences were found in relative metatarsal lengths between the
      groups. These findings indicate that older people with forefoot pain generate
      higher peak plantar pressures under the lateral metatarsal heads when walking,
      but do not exhibit relatively longer lesser metatarsals. Other factors may be
      responsible for the observed pressure increase, such as reduced range of motion
      of the metatarsophalangeal joints and increased stiffness of plantar soft
      tissues.

PMID- 22987210
TI  - Efficacy of a brief HIV prevention counseling intervention among STI clinic
      patients in Russia: a randomized controlled trial.
AB  - The study examined the efficacy of a brief theory-based counseling intervention
      to reduce sexual HIV risk behaviors among STI clinic patients in St. Petersburg,
      Russia. Men and women (n = 307) were recruited to receive either: (1) a 60-minute
      motivational/skills-building counseling session dealing with sexual HIV risk
      reduction, or (2) written HIV prevention information material. Participants
      completed baseline, three- and six-month assessments in the period between July
      2009 and May 2011. Compared to the control group, the face-to-face counseling
      intervention showed significant increases in the percentage of condom use and
      consistent condom use, and significant decreases in the number of unprotected
      sexual acts and frequency of drug use before sex. Intervention effects dissipated
      by 6 months. The brief counseling intervention may effectively reduce HIV sexual
      risk behaviors and enhance protective behaviors among STI clinic patients in
      Russia. Short-term positive effects were achieved with a single one hour
      counseling session.

PMID- 22987211
TI  - DNA polymerases in nonhomologous end joining: are there any benefits to standing
      out from the crowd?
AB  - Chromosome breaks, often with damaged or missing DNA flanking the break site, are
      an important threat to genome stability. They are repaired in vertebrates
      primarily by nonhomologous end joining (NHEJ). NHEJ is unique among the major DNA
      repair pathways in that a continuous template cannot be used by DNA polymerases
      to instruct replacement of damaged or lost DNA. Nevertheless, at least 3 out of
      the 17 mammalian DNA polymerases are specifically employed by NHEJ. Biochemical
      and structural studies are further revealing how each of the polymerases employed
      by NHEJ possesses distinct and sophisticated means to overcome the barriers this
      pathway presents to polymerase activity. Still unclear, though, is how the
      resulting network of overlapping and nonoverlapping polymerase activities
      contributes to repair in cells.

PMID- 22987212
TI  - Selective activation of group III metabotropic glutamate receptor subtypes
      produces different patterns of gamma-aminobutyric acid immunoreactivity and
      glutamate release in the retina.
AB  - Glutamate, the major excitatory neurotransmitter in the retina, functions by
      activation of both ionotropic (iGluR) and metabotropic (mGluR) glutamate
      receptors. Group III mGluRs, except for mGluR6, are mostly found in the inner
      plexiform layer (IPL), and their retinal functions are not well known. Therefore,
      we decided to investigate the effect of mGluRIII on glutamate release and
      GABAergic amacrine cells in the chick retina. The nonselective mGluRIII agonist L
      SOP promoted a decrease in the number of gamma-aminobutyric acid (GABA)-positive
      cells and in the GABA immunoreactivity in all sublayers of the IPL. This effect
      was prevented by the antagonist MAP-4, by GAT-1 inhibitor, and by antagonists of
      iGluR. Under the conditions used, L-SOP did not alter endogenous glutamate
      release. VU0155041, an mGluR4-positive allosteric modulator, reduced GABA
      immunoreactivity in amacrine cells and in sublayers 2 and 4 of the IPL but evoked
      an increase in the glutamate released. VU0155041's effect was inhibited by the
      absence of calcium. AMN082, a selective mGluR7-positive allosteric modulator,
      also decreased GABA immunoreactivity in amacrine cells and sublayers 1, 2, and 3
      and increased glutamate release, and this effect was also inhibited by calcium
      absence. DCPG, an mGluR8-selective agonist, did not significantly alter GABA
      immunoreactivity in amacrine cells or glutamate release. However, it did
      significantly increase GABA immunoreactivity in sublayers 4 and 5. The results
      suggest that mGluRIIIs are involved in the modulation of glutamate and GABA
      release in the retina, possibly participating in distinct visual pathways: mGluR4
      might be involved with cholinergic circuitry, whereas mGluR7 and mGluR8 might
      participate, respectively, in the OFF and the ON pathways.

PMID- 22987213
TI  - Real-time histology of colon polyps--is it ready for prime time?

PMID- 22987214
TI  - Warm water infusion colonoscopy: a review and meta-analysis.
AB  - BACKGROUND AND STUDY AIMS: Warm water infusion instead of traditional air
      insufflation during the insertion phase of colonoscopy has been proposed to
      reduce pain and improve patient acceptance of the procedure. This systematic
      review aimed to compare warm water infusion with standard air insufflation
      according to findings from randomized controlled trials (RCTs). METHODS: In a
      systematic review and meta-analysis of RCTs comparing warm water infusion with
      standard air insufflation, primary outcome measures were procedure-related (cecal
      intubation, time to cecal intubation, and adenoma detection rates) and patient
      related (pain). RESULTS: Nine studies (1283 patients) were included. Warm water
      infusion, as sole modality for facilitating insertion, was associated with a
      fourfold higher risk of cecal intubation failure compared with air insufflation
      (risk ratio [RR] 4.01, confidence interval [CI] 1.17 to 13.78, P = 0.03), but
      this risk did not significantly differ between warm water infusion and air
      insufflation with the hybrid technique (i. e., brief use of air when difficulty,
      e. g. poor view, was encountered). Warm water infusion and air insufflation were
      associated with similar cecal intubation times (P = 0.62) and adenoma detection
      rates (P = 0.49), but with warm water infusion patients experienced significantly
      less pain (P < 0.00001) and a significantly lower proportion requested sedation
      and/or analgesia (RR 0.48, CI 0.35 to 0.66, P < 0.00001). CONCLUSIONS: Although
      failure of cecal intubation is more frequent with warm water infusion, technical
      modifications, i. e., short air insufflations, can abolish this. Warm water
      infusion is less painful than standard air insufflation, reduces the need for
      sedation/analgesia, and improves patient acceptance of colonoscopy, without
      additional adverse reactions.

PMID- 22987215
TI  - Gastric extremely well-differentiated intestinal-type adenocarcinoma: a
      challenging lesion to achieve complete endoscopic resection.
AB  - Extremely well-differentiated tubular adenocarcinomas (EWDAs) of the stomach are
      characterized by surface maturation and their mimicking of intestinal metaplasia.
      Endoscopically, intramucosal EWDAs are frequently ill defined with indistinct
      borders due to the pallor of the neoplastic mucosa and the lack of contrast
      against the background atrophic and metaplastic mucosa. We evaluated the
      effectiveness of endoscopic resection for EWDAs after endoscopic submucosal
      dissection (ESD). Among 872 patients with early gastric cancer, 17 EWDAs were
      identified (1.9 %). Endoscopically, the flat or depressed type was significantly
      more common among EWDAs (88.2 %) than among early gastric cancers of other
      histologies (37.8 %; P < 0.01). The discrepancy between endoscopically estimated
      tumor size and tumor size as confirmed in pathology reports was significantly
      greater among EWDAs (18.4 +/- 22.0  mm) than among others (5.8 +/- 7.5  mm).
      Involvement of the lateral resection margin was more common (29.4 % vs. 2.5 %; P
      < 0.05), and complete resection was achieved less often in EWDAs (47.1 % vs. 80.4
      %; P = 0.01) compared to the others. EWDAs are associated with higher rates of
      incomplete resection after ESD, especially along the lateral margins.
      Pathologists should alert endoscopists when this diagnosis is made, with its
      associated risks; and endoscopists should pay particular attention to the extent
      of these tumors during resection.

PMID- 22987216
TI  - Endoscopic submucosal dissection with sentinel node navigation surgery for early
      gastric cancer.
AB  - We combined endoscopic submucosal dissection (ESD) and sentinel node navigation
      surgery with the purpose of achieving complete resection of early gastric cancer
      while preserving the organ and assessing pathological nodal status. A total of 13
      patients with cT1( <= 3 cm)N0 early gastric cancer underwent combined ESD and
      sentinel node navigation surgery (ESN) at a single tertiary referral center.
      Sentinel node navigation surgery using indocyanine green was performed during ESD
      and all suspected sentinel nodes were removed laparoscopically and examined
      intraoperatively. ESN was converted to gastrectomy with D2 dissection if there
      was evidence of metastasis on frozen section. ESN was completed in 12 patients
      and in 1 patient was converted to gastrectomy after sentinel node navigation
      surgery. En bloc tumor resection was achieved in all cases. Two patients
      underwent additional gastrectomy because they had tumor-positive vertical
      margins. In all cases ESN was conducted without intraoperative or postoperative
      adverse events. ESN is a feasible minimally invasive procedure that allows en
      bloc tumor resection to be achieved while assessing the pathological status of
      the lymph nodes.

PMID- 22987217
TI  - Quality in screening colonoscopy: position statement of the European Society of
      Gastrointestinal Endoscopy (ESGE).

PMID- 22987219
TI  - A continuing debate on 6-minute withdrawal time as a quality indicator during
      colonoscopy.

PMID- 22987220
TI  - Small bowel endoscopic exploration Spanish GI endoscopy society recommendations.

PMID- 22987221
TI  - Variations in the ceramide profile in different seasons and regions of the body
      contribute to stratum corneum functions.
AB  - The objective of this study was to clarify variations of the ceramide (CER)
      profile in human stratum corneum (SC) in different seasons and in different
      regions of the body and to estimate the contributions of CERs to the SC barrier
      and water-holding functions. Based on the information that there are great
      variations of SC functions among body sites, we compared the CER profiles
      obtained from ten different anatomical sites in healthy Japanese males in four
      seasons. Not only the physiological parameters of skin but also the CER profile
      showed body region and seasonal variations. The total CER level, the CER
      composition and the C34-CER[NS] species displayed strong correlations with the
      values of transepidermal water loss and capacitance throughout the body.
      Especially in the cheek, a strong correlation between the capacitance and the CER
      profile was observed. There were seasonal variations of the CER profile in the
      lip, upper arm and palm. Our results indicate that regional and seasonal
      variations of the CER profile may contribute to SC functions.

PMID- 22987222
TI  - Smokeless tobacco and risk of head and neck cancer: evidence from a case-control
      study in New England.
AB  - Current studies suggesting that smokeless tobacco use increases the risk of head
      and neck cancer are hampered by small numbers. Consequently, there remains
      uncertainty in the magnitude and significance of this risk. We examined the
      relationship between smokeless tobacco use and head and neck squamous cell
      carcinoma (HNSCC) in a population-based case-control study with 1,046 cases and
      1,239 frequency-matched controls. Logistic regression models were used to
      estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for
      age, gender, race, education level, cigarette smoking, and alcohol consumption. A
      nonsignificant elevated association between having ever used smokeless tobacco
      and HNSCC risk (OR = 1.20, 95% CI: 0.67-2.16) was observed. Individuals who
      reported 10 or more years of smokeless tobacco use had a significantly elevated
      risk of HNSCC (OR = 4.06, 95% CI: 1.31-12.64), compared to never users. In an
      analysis restricted to never cigarette smokers, a statistically significant
      association was observed between ever use of smokeless tobacco and the risk of
      HNSCC (OR = 4.21, 95% CI: 1.01-17.57). These findings suggest that long-term use
      of smokeless tobacco increases the risk of HNSCC.

PMID- 22987223
TI  - Prenatal genetic counseling and consanguinity.
AB  - OBJECTIVES: To evaluate the prevalence of consanguineous patients at a Western
      European prenatal genetic counseling clinic and to describe demographic as well
      as health-related characteristics of this patient group. METHOD: Retrospective
      analysis of 1964 primary consultations at the Prenatal Genetic Counseling
      Outpatient Clinic at the Medical University of Vienna General Hospital in
      Austria. Characteristics of consanguineous patients were compared with those of a
      control group of not-related unions. RESULTS: A total of 8.9% (174/1964) of all
      patients lived in a consanguineous union, meaning they were related as second
      cousin or closer [78.7% (137/174) first cousin, 14.4% (25/174) second cousin,
      6.3% (11/174) first cousin once removed or 0.6% (1/174) uncle/niece].
      Consanguineous patients were significantly younger (26.6 +/- 5.4 vs 30.4 +/- 6.5,
      p < 0.01) and of non-Austrian background [92.5% (161/174) vs 32.8% (57/174), p <
      0.01] than not-related controls. Forty-six per cent (80/174) were referred during
      an ongoing pregnancy. The main counseling issue was family history of
      consanguinity (ICD Z84.3) in 31.6% (55/174) of cases. CONCLUSIONS: Estimations of
      the prevalence of consanguinity among the general population in Western Europe
      likely highly underestimate the evaluated prevalence among patients referred for
      prenatal genetic counseling. Counseling strategies need to take into
      consideration that consanguineous patients are more likely to be young and have
      an immigrant background.

PMID- 22987224
TI  - A structural powder diffraction study of two polymorphic forms of nortriptyline
      hydrochloride.
AB  - Nortriptyline hydrochloride, a tricyclic antidepressant, appears in two different
      polymorphic forms, only one of which (hereafter, form beta) has been previously
      characterized by single-crystal analysis. Form beta is monoclinic, P2(1)/c, with
      a = 5.070(2), b = 34.088(5), c = 9.976(1) A, and beta = 90.74(2) degrees . A
      second crystalline form (the alpha form) has now been characterized by structural
      powder diffraction methods (using both laboratory and synchrotron radiation
      diffraction data). Form alpha crystallizes in the monoclinic P2/c space group, a
      = 9.99126(6), b = 5.10021(3), c = 34.1636(1) A, and beta = 98.684(6) degrees .
      The thermodynamic relationship between the two forms has been determined by
      differential scanning calorimetry analysis and variable-temperature
      thermodiffractometric experiments, revealing that the two forms are
      monotropically related and form alpha is more stable. Both phases are
      characterized by a sequence of hydrogen-bonded N-protonated molecules, which, in
      the two crystalline environments, adopt the same conformation. The difference
      between the two crystals can be traced back to the supramolecular arrangement
      characterized by one-dimensional chains, built by homochiral molecules (for
      conformationally driven chirality) in the alpha form, and by enantiomeric ones in
      the beta form. This observation nicely explains why, upon heating, solid-solid
      interconversion between the two forms does not occur.

PMID- 22987225
TI  - Expression of leptin and its long-form receptor in the marginal cutaneous tissues
      of diabetic foot ulcers.
AB  - To investigate the relationship between the expression of leptin and its long
      form receptor, OB-RL, and wound healing in diabetic foot ulcers. Biopsies from 10
      patients with diabetic foot ulcers (DU group), 10 with non-diabetic foot ulcers
      (NDU group), and 10 with normal skin (normal control, NC group) were examined.
      Leptin and OB-RL mRNA and protein levels were assessed using RT-PCR and
      immunohistochemistry analyses, respectively. The cuticle thickness was
      significantly greater, and the epidermal layer was significantly lesser in the DU
      and NDU groups. Leptin protein expression was significantly higher in the DU and
      NDU than NC group (P < 0.001), whereas OB-RL mRNA and protein expressions were
      significantly lower in the DU group and significantly higher in the NDU group (P
      < 0.001). Diabetic foot ulcer duration was negatively correlated with OB-RL
      protein expression (rho = -0.671, P = 0.034). Decreased OB-RL may result in
      reduced leptin signaling in diabetic foot ulcers. Further studies are required to
      determine whether OB-RL levels are related to the prognosis of diabetic foot
      ulcers, as well as to explore the use of leptin or mimetics for promoting ulcer
      healing.

PMID- 22987226
TI  - Time to rethink screening for abdominal aortic aneurysm?

PMID- 22987227
TI  - NMR assignments for the telokin-like domain of bacteriophage P22 coat protein.
AB  - The bacteriophage P22 virion is assembled from identical coat protein monomers in
      a complex reaction that is generally conserved among tailed, double-stranded DNA
      bacteriophages and viruses. Many coat proteins of dsDNA viruses have structures
      based on the HK97 fold, but in some viruses and phages there are additional
      domains. In the P22 coat protein, a "telokin-like" domain was recently
      identified, whose structure has not yet been characterized at high-resolution.
      Two recently published low-resolution cryo-EM reconstructions suggest markedly
      different folds for the telokin-like domain that lead to alternative conclusions
      about its function in capsid assembly and stability. Here we report (1)H, (15)N,
      and (13)C NMR resonance assignments for the telokin-like domain. The secondary
      structure predicted from the chemical shift values obtained in this work shows
      significant discrepancies from both cryo-EM models but agrees better with one of
      the models. In particular, the functionally important "D-loop" in one model shows
      chemical shifts and solvent exchange protection more consistent with beta-sheet
      structure. Our work will set the basis for a high-resolution NMR structure
      determination of the telokin-like domain that will help improve the cryo-EM
      models, and in turn lead to a better understanding of how coat protein monomers
      assemble into the icosahedral capsids required for virulence. 

PMID- 22987228
TI  - NMR assignments of SPOC domain of the human transcriptional corepressor SHARP in
      complex with a C-terminal SMRT peptide.
AB  - The transcriptional corepressor SMRT/HDAC1-associated repressor protein (SHARP)
      recruits histone deacetylases. Human SHARP protein is thought to function in
      processes involving steroid hormone responses and the Notch signaling pathway.
      SHARP consists of RNA recognition motifs (RRMs) in the N-terminal region and the
      spen paralog and ortholog C-terminal (SPOC) domain in the C-terminal region. It
      is known that the SPOC domain binds the LSD motif in the C-terminal tail of
      corepressors silencing mediator for retinoid and thyroid receptor (SMRT)/nuclear
      receptor corepressor (NcoR). We are interested in delineating the mechanism by
      which the SPOC domain recognizes the LSD motif of the C-terminal tail of
      SMRT/NcoR. To this end, we are investigating the tertiary structure of the
      SPOC/SMRT peptide using NMR. Herein, we report on the (1)H, (13)C and (15)N
      resonance assignments of the SPOC domain in complex with a SMRT peptide, which
      contributes towards a structural understanding of the SPOC/SMRT peptide and its
      molecular recognition. 

PMID- 22987229
TI  - 1H, 13C and 15N resonance assignments of TFIIS2-1 PWWP domain from Trypanosoma
      brucei.
AB  - TFIIS2-1, one of the two trypanosome homologues of transcription elongation
      factor TFIIS (TbTFIIS1, TbTFIIS2-1), with a PWWP domain in the N-terminus, has a
      possible association with the largest subunit of RNA polymerase II (RPB1) and
      shares an essential function with TbTFIIS1 in the growth of Trypanosoma brucei.
      Here we report the resonance assignments of the protein backbone of the PWWP
      domain of TFIIS2-1 from T. brucei. 

PMID- 22987230
TI  - Erythema persists longer than one year in split-thickness skin graft donor sites.
AB  - The recovery of skin function and appearance after harvest of split-thickness
      skin autografts is incompletely described. We followed the kinetics of skin
      restoration after a partial-thickness skin excision relative to adjacent normal
      skin over 12 months. Standardized donor site wounds were made on the thigh using
      a pneumatic dermatome in 19 consecutive Caucasian patients, median age 70 years,
      age range 44-86 years, who were undergoing skin graft surgery for leg ulcers.
      Transepidermal water loss (TEWL), erythema and pigmentation were measured
      quantitatively using non-invasive devices. The macroscopically healed wound was
      compared with adjacent normal skin at 1, 3 and 12 months. At 1 month
      postoperatively, TEWL was 108% (p = 0.003), erythema 145% (p < 0.0005) and
      pigmentation 24% (p < 0.001) higher in the wounds compared with adjacent
      uninjured skin. The corresponding values at 3 months were 48% (p = 0.015), 89% (p
      < 0.0005) and 15% (p < 0.0005). After 12 months, erythema was elevated by 36% (p
      < 0.0005), while TEWL (p = 0.246) and pigmentation (p = 0.211) had returned to
      same levels as in the surrounding normal skin. Diabetes mellitus (p = 0.024) and
      smoking (p = 0.017) were associated with increased TEWL of normal skin, and
      erythema decreased with age (rs = -0.53, p = 0.020). In conclusion, erythema
      appears to be the significant component contributing to long-term postoperative
      donor site appearance. We hypothesize that this is due to increased
      microvasculature.

PMID- 22987231
TI  - Anomalous high bifurcation of the common femoral artery at the groin: management
      of GSV incompetence with endovenous laser ablation.
AB  - OBJECTIVES: To discuss safety of EVLA in anomalies of the GSV anatomy. To review
      and discuss complications of surgery involving anomalous anatomy. METHOD: We
      report a case of high bifurcation of the common femoral artery wrapping around
      the saphenofemoral junction. RESULTS: Successful ablation was achieved with no
      adverse consequences. CONCLUSION: EVLA is a safe treatment for SFJ/GSV
      incompetence in the presence of vascular anomalies that have historically
      resulted in serious vascular complications from surgery.

PMID- 22987232
TI  - Early arteriovenous fistula after radiofrequency ablation of long saphenous vein.
AB  - A 75-year-old woman developed an arteriovenous fistula (AVF) between the common
      femoral artery and common femoral vein following radiofrequency ablation (RFA) of
      left long saphenous vein. Failed coil embolization of the AVF was followed by
      successful surgical ligation. Awareness of the aetiology of this uncommon
      complication of RFA and its treatment options is important with the increasing
      use of RFA for varicose vein treatment. 

PMID- 22987234
TI  - Compressive syndrome of internal jugular veins in multiple sclerosis: does it
      matter?
AB  - OBJECTIVES: Condition known as chronic cerebrospinal venous insufficiency (CCSVI)
      is characterized by insufficient cerebral vein drainage in patients with multiple
      sclerosis (MS) and internal jugular vein (IJV), vertebral and/or azygos veins
      stenoses. However, external compression on the IJV was not clearly described as a
      potential cause of CCSVI. We aim to present a case of CCSVI in a patient with MS
      caused by bilateral IJV inverted valves combined with IJV external compression by
      carotid bulb. METHODS: A 31-year-old female patient was admitted to our institute
      for IJV and vertebral veins morphological and haemodynamical assessment after
      being treated for MS for the last 14 years. Colour Doppler ultrasonography showed
      right IJV prestenotic dilation and inverted valves in both IJV. Computerized
      tomography angiography showed bilateral IJV compression by carotid bulb.
      Haemodynamical Doppler parameters showed that external IJV compression
      significantly contributed to CCSVI occurrence. RESULTS: Bilateral IJV confluence
      percutaneous angioplasty (PTA) was done, and the patient was discharged for
      further neurological examination. Partial carbon dioxide pressure was
      significantly lower in the distal part of both IJV following PTA and oxygen
      saturation increased. CONCLUSION: In the case presented, PTA of the IJV
      confluence resulted in haemodynamic improvement despite the presence of IJV
      external compression.

PMID- 22987233
TI  - Abnormal expression of Tie1 on the valves of great saphenous varicose vein.
AB  - OBJECTIVE: To investigate the abnormal expressions of Tie1 on the valves of great
      saphenous varicose vein, and to discuss the relationship between the phenomenon
      and pathogenesis of varicose vein of lower extremity. METHODS: Varicose veins
      group 18 samples, normal control group 14 samples. Immunohistochemistry staining
      has investigated the expression of CD31 and Tie1 in the first valves of great
      saphenous veins. Semi-quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) has checked mRNA expression of Tie1. Western blot has checked
      the expression of Tie1 protein in venous valves. RESULTS: In normal control group
      valves, there was no difference between proximal and distal sides endothelium,
      which expressing CD31 in both valvar basement and valve cusp (positive
      endothelial cells [ECs] percentage: P > 0.05, P > 0.05). However, the endothelium
      of the proximal side demonstrates Tie1 stronger than distal side in valvar
      basement (positive ECs percentage: P < 0.05), which was not found at valve cusp
      (positive ECs percentage: P > 0.05). In varicose veins group, the endothelium of
      proximal side cells expresses CD31 weaker than distal side at both valvar
      basement and valve cusp (positive ECs percentage: P < 0.05, P < 0.05) besides the
      morphological alteration of valves. Moreover, it expresses Tie1 much weaker than
      diatal side (positive ECs percentage: P < 0.01). Semi-quantitative RT-PCR showed
      that valves of varicose veins group expressed Tie1 much weaker than the normal
      control group (P < 0.01). Western blot could not detect the expression of Tie1 in
      venous valves. CONCLUSION: The decreasing expression of Tie1 may play an
      important role in the pathogenesis of primary lower extremity varicose veins.

PMID- 22987235
TI  - Gold-catalyzed cyclization-cycloaddition cascade reactions of allenyl acetals
      with nitrones.
AB  - Gold and silver: when allenyl acetals and nitrones are treated with a catalytic
      amount of a gold complex and a silver salt they react through a cyclization
      cycloaddition cascade reaction to give a mixture of diastereomeric tricyclic
      products. The mixture converges to a single product upon acid hydrolysis. The key
      intermediate is postulated to be a 1-methoxyfulvene species.

PMID- 22987236
TI  - Reverse altitudinal cline in cold hardiness among Erebia butterflies.
AB  - There is strong evidence for a shifting of range boundaries by many temperate
      butterfly species to higher altitudes and latitudes. Climate change represents a
      potential threat to mountain fauna. Nevertheless, information on ecophysiological
      limits of individual species is scarce.  We studied the lower thermal limits of
      four species representing the prevailingly mountain Holarctic butterfly genus
      Erebia. We measured the cold tolerance of hibernating larvae, namely the
      supercooling point (SCP) and the lower lethal temperature (LLT). Three mountain
      species were freeze avoiding, with various levels of SCP (-8 to -22 degree C),
      and LLT close to SCP. The only exception was lowland E. medusa, whose
      caterpillars were freeze tolerant with LLT (-21 degree C) slightly below its SCP
      (-17 degree C). Surprisingly, LLT was highest in the alpine E. tyndarus and
      lowest in E. medusa inhabiting lower altitudes with higher mean winter
      temperatures. We explain the observed reversed altitudinal cline in cold
      hardiness by the buffering function of snow cover in the hibernacula of
      caterpillars that is strong at high mountains but irregular, unpredictable and
      thus unreliable in lowlands.

PMID- 22987237
TI  - Cryopreservation of Lomandra sonderi (Asparagaceae) shoot tips using droplet
      vitrification.
AB  - A cryopreservation protocol was developed for Lomandra sonderi (Asparagaceae), an
      endemic plant of southwest Western Australia used for mine site restoration.
      Thermal analysis of L. sonderi shoot tips using differential scanning calorimetry
      was used to detect the formation of ice in shoot tips and consequently allowed
      optimisation of the time of incubation in plant vitrification solution 2 (PVS2),
      which attempted to minimise phytotoxicity of, and excessive dehydration by, its
      cryoprotective components. Sugar pretreatments did not improve survival. Use of a
      loading solution containing 2 M glycerol and 0.4 M sucrose prior to incubation in
      PVS2 improved survival of control shoot tips. Preconditioning at 20+/-1 degree C
      day/night alternating temperature with a 16 h photoperiod or at a constant 5
      degree C temperature with a 12 h photoperiod both significantly improved both
      control shoot tip survival and post-cryopreservation survival. Shoot tips that
      recovered from liquid nitrogen immersion were successfully re-established as
      actively growing in vitro plantlets.

PMID- 22987238
TI  - 'Personalisation' of droplet-vitrification protocols for plant cells: a
      systematic approach to optimising chemical and osmotic effects.
AB  - Although an appropriate cryopreservation protocol is a prerequisite for basic
      studies and large-scale implementation as well as further cryopreservation
      studies, the process relies on trial and error. Among the vitrification-based
      cryopreservation techniques, droplet-vitrification produces high post
      cryopreservation recovery. However, the protocol itself cannot solve the problems
      engaged in plant cryopreservation, prominently due to dehydration with cytotoxic
      vitrification solutions. This paper proposes a set of treatments to develop
      droplet-vitrification using a standard procedure associated with additional
      treatments and alternative vitrification solutions. The proposed standard
      protocol consists of a progressive preculture with 0.3 M sucrose for 31 h and
      with 0.7 M for 17 h, loading with vitrification solution C4-35% (17.5 percent
      glycerol + 17.5 percent sucrose, w/v) for 20 to 40 min, dehydration with
      vitrification solutions A3-90 percent (37.5 percent glycerol + 15% DMSO + 15
      percent EG + 22.5 percent sucrose) for 10 to 30 min or B1-100 percent (PVS3) for
      40 to 120 min at room temperature, cooling the samples using aluminum foil
      strips, rewarming by plunging into pre-heated (40 degree C) unloading solution
      (0.8 M sucrose) and further unloading for 20 to 60 min, depending on size and
      permeability of the materials. Using this systematic approach we can identify
      whether the material is tolerant or sensitive to chemical toxicity and to the
      osmotic stress of dehydration with vitrification solutions, thus revealing which
      is the main barrier in solution-based vitrification methods. Based on the
      sensitivity of samples we can design a droplet-vitrification procedure, i.e.
      preculture, loading, dehydration with vitrification solutions, cooling and
      rewarming. Using this approach, the development of appropriate droplet
      vitrification protocol is facilitated.

PMID- 22987239
TI  - Multi-decadal survival of an Antarctic nematode, Plectus murrayi, in a -20
      degrees C stored moss sample.
AB  - It is not clear for how long Antarctic soil nematodes might tolerate freezing.
      Samples of the Antarctic moss, Bryum argenteum, were collected on 1 October 1983
      at Langhovde, Soya coast, eastern Antarctica and were stored at -20 degrees C.
      After 25.5 years of storage, living nematodes were recovered from the samples and
      were identified as Plectus murrayi by morphological examination and nucleotide
      sequencing of ribosomal RNA loci. The nematodes can grow and reproduce in a water
      agar plate with bacteria (mainly Pseudomonas sp.) cultured from the moss extract.
      They showed freezing tolerance at -20 degrees C and -80 degrees C and their
      survival rate after exposure to -20 degrees C, but not -80 degrees C, was
      increased if they were initially frozen slowly at a high sub-zero temperature.
      They also showed some ability to tolerate desiccation stress.

PMID- 22987240
TI  - Proteomic expression of microfungal ripening starter Geotrichum candidum
      submitted to cold stress is strain-dependent: studies using 2d-dige technology
      and samespots software analysis.
AB  - Geotrichum candidum is a micro-fungus widely used as a ripening starter in cheese
      making. In anthropogenic environments such as dairy industries, this
      microorganism is subjected to many environmental and technological stresses
      including low temperature exposure. Our aim was to study the proteomic response
      of G. candidum to cold stress using a comparative proteomic approach by two
      dimensional Differential In Gel Electrophoresis (2D DIGE). This technique
      consists on the labeling of proteins by specific fluorescent dyes (CyDyes). The
      results, obtained with G. candidum cells subjected to cold temperature, show
      significant proteomic patterns differences compared with the standard conditions.
      Furthermore, this biochemical response seems strain specific. 2D DIGE technology
      combined with SameSpotsTM software analysis support these results through an
      important statistical validity. The comparative studies in a single gel, using
      two different fluorescent CyDyes (Cy3 and Cy5), lead to proteins differentiation.
      Selected spots were treated and analyzed by mass spectrometry.

PMID- 22987241
TI  - The effect of cryopreservation on genomic stability in strains of the fungus
      Trichoderma.
AB  - Within Biological Resource Collections, the successful long-term storage of
      fungal cultures is essential because of their scientific and potential commercial
      value. Preservation procedures such as cryopreservation have traditionally been
      used to ensure genomic stability due to the suspension of metabolic activity at
      ultra-low temperatures. Genomic integrity is important with regards to
      conservation, as changes in the genome may compromise production of a desired
      metabolite, enzyme or activity. To evaluate cryopreservation as a conservation
      protocol, genomic integrity was assessed in five strains of the economically
      important fungus Trichoderma. Two polymerase chain reaction (PCR) fingerprinting
      techniques commonly used for molecular studies of fungi were applied. Three
      genetic polymorphisms were detected amongst replicates post preservation,
      indicating that even robust, standardised preservation cryopreservation
      methodologies can sometimes induce genomic change. However, the low number of
      polymorphisms suggests that cryopreservation is a reliable method for organism
      storage over long periods of time.

PMID- 22987242
TI  - The effects of trehalose and sucrose on frozen spermatozoa of Yunnan semi-fine
      wool sheep during a non-mating season.
AB  - To improve the quality of frozen spermatozoa of Yunnan semi-fine wool sheep, the
      protective effect of trehalose and sucrose on frozen ram spermatozoa during a non
      mating season was evaluated and compared in this study. Briefly, following
      collection by electric stimulation, equilibration at  degree C following dilution
      with the freezing extender, and pre-freezing in liquid nitrogen vapor, the ram
      spermatozoa were frozen in liquid nitrogen. After thawing, viability, motility,
      acrosome status, membrane integrity, and phosphatidylserine (PS) distribution was
      determined using a computer-assisted spermatozoa analysis system and flow
      cytometry. The data indicated disaccharide can improve the quality of frozen ram
      spermatozoa. With a trehalose concentration of 100mM, the post-thaw viability and
      motility (80.56 +/- 6.89% and 46.07 +/- 5.84 %) of ram spermatozoa were
      significantly more than those of ram spermatozoa frozen with no disaccharide
      (65.46 +/- 18.96 % and 34.62 +/- 9.32%, P<0.05). However, the effect of sucrose
      on the viability, motility, and moving velocity of ram spermatozoa was similar to
      that of the control group (p > 0.05). Compared with sucrose, trehalose can
      significantly increase the motility of frozen ram spermatozoa (p<0.05). In
      addition, addition of trehalose or sucrose can efficiently protect the acrosome
      of frozen spermatozoa. Moreover, when the concentration of trehalose or sucrose
      was 100mM, the protective effect of trehalose or sucrose on the membrane
      integrity and PS distribution was significantly higher than that of the control
      group (p>0.05). However, the protective effect of trehalose on viability, moving
      velocity, acrosome status, membrane integrity, and PS distribution of frozen ram
      spermatozoa was similar to that of sucrose (p>0.05). In conclusion, the
      protective effect of trehalose on frozen sheep spermatozoa is superior to that of
      sucrose. Addition of 100mM of trehalose in the freezing extenders can improve the
      post-thaw quality of ram spermatozoa with respect to viability, motility, and
      linear velocity. Moreover, presence of disaccharide can protect acrosome and
      membrane of frozen sheep spermatozoa.

PMID- 22987243
TI  - Long-term preservation of chilled canine semen using vitamin C in combination
      with green tea polyphenol.
AB  - Vitamin C and green tea polyphenol are known to have antioxidant effects. The aim
      of this study was to evaluate the quality of canine semen after preservation with
      diluents containing vitamin C and polyphenol at 5 degree C for 4 weeks. In
      experiment 1, we investigated the effects of vitamin C combined with polyphenol
      supplementation on chilled semen quality. The addition of vitamin C (0.5 or 1 mM)
      with 0.75 mg per mL polyphenol to semen extender provided significantly higher
      percentages of sperm motility and viability during cold storage compared to
      unsupplemented semen. In experiment 2, we determined the optimal working
      concentration of vitamin C in the semen extender by comparison of a range of
      concentrations between 0.1 and 20 mM. Supplementation of 0.5 mM vitamin C plus
      polyphenol yielded the highest percentages of sperm motility and viability;
      however, there was no beneficial effect on the plasma membrane and acrosomal
      integrity of the spermatozoa.

PMID- 22987244
TI  - Interaction of serum ferritin and body mass index in patients with chronic
      hepatitis B: improved prediction of cirrhosis.

PMID- 22987245
TI  - Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression
      of myostatin in a rat heart failure model.
AB  - BACKGROUND: In chronic heart failure (CHF), cachexia is a hallmark of the
      terminal stage of this disease and is associated with a severely reduced quality
      of life and poor prognosis. Therapeutic options are currently not available.
      Ghrelin and its analogues BIM-28125 and BIM-28131 (now known as RM-131) have been
      shown to increase weight in a rat model of CHF. It has been further demonstrated
      that the expression of myostatin, a negative regulator of skeletal muscle mass,
      is increased in CHF. The aim of the study was to investigate the influence of
      ghrelin or its analogues on myostatin in CHF. METHODS: In an animal model of CHF,
      Sprague-Dawley rats received either ghrelin or two ghrelin analogues BIM-28125
      and BIM-28131 in two different concentrations (50 and 500 nmol/kg/day) compared
      to placebo. The compounds were delivered using osmotic mini pumps. The expression
      of myostatin was analyzed in skeletal muscle by RT-PCR and Western blot, and
      muscle mass of gastrocnemius muscle was measured. The plasma levels of tumor
      necrosis factor alpha (TNF-alpha) were measured. RESULTS: The relative weight of
      the gastrocnemius muscle of the sham-operated group was significantly increased
      compared to placebo-treated CHF rats. The application of ghrelin analogue BIM
      28125 and BIM-28131 in their higher concentrations led to a significant reduction
      in myostatin mRNA expression in comparison to placebo. Myostatin protein
      expression was significantly reduced in both concentrations of ghrelin and BIM
      28131 and in the lower concentration of BIM-28125. The increase of TNF-alpha
      plasma concentration in the CHF-animals could be abolished by all used
      substances. CONCLUSIONS: In an animal model of CHF, the expression of myostatin
      is significantly reduced in the skeletal muscle after application of ghrelin and
      most concentrations of its analogues BIM-28125 and BIM-28131 possibly due to anti
      inflammatory effects.

PMID- 22987246
TI  - Will GM animals follow the GM plant fate?
AB  - Despite being both Genetically Modified Organisms (GMOs), GM plants and GM
      animals share few similarities outside the laboratory premises. Whilst GM plants
      were soon embraced by industry and became a commercial success, only recently
      have GM animals reached the market. However, an area where GM animals are likely
      to follow the GM plant path is on their potential to cause social unrest. One of
      the major flaws of the 90s GMO crisis was the underestimation of the influence
      that different players can have in the adoption of new biotechnological
      applications. In this article we describe the unique evolution of GM animals in
      two of the most important fields: the pharmaceutical and the breeding sectors.
      For our analysis, we have subdivided the production chain into three governance
      domains: Science, Market and Public. We describe the influence and interaction of
      each of these domains as a vehicle for predicting the future adoptability of GM
      animals and to highlight conflicting areas.

PMID- 22987247
TI  - MRI characteristics of lipoma and atypical lipomatous tumor/well-differentiated
      liposarcoma: retrospective comparison with histology and MDM2 gene amplification.
AB  - PURPOSE: To review the reliability of MR imaging features for the purpose of
      distinguishing lipoma and atypical lipomatous tumor/well-differentiated
      liposarcoma (ALT/WDL). MATERIALS AND METHODS: A retrospective review of 87
      patients with histologically proven lipomatous tumors was performed. All
      underwent MR imaging, assessing lipomatous content, septation, and nodules. The
      associations between these features and tumor diagnosis based on morphology and
      the presence or absence of MDM2 amplification were explored. The age of the
      patient and the size and location of the lesion were also recorded for
      statistical analysis. RESULTS: Of the 87 patients, 54 were classified as lipomas
      and 33 as ALT/WDL. MR identified ALT/WDL with a sensitivity of 90.9 % (CI 74.5
      97.6) and a specificity of 37.0 % (CI 24.6-51.3). The positive and negative
      predictive values were 46.9 % (CI 34.5-59.7) and 86.9 % (CI 65.3-96.6),
      respectively. The mean age of patients with ALT/WDL was greater (60 years [range
      40-83 years]) than those with lipoma (52 years [range 10-79 years]) (p = 0.025).
      The mean size of ALT/WDL (18.7 cm [range 5-36 cm]) was significantly greater than
      lipoma (13.9 cm [range 3-32 cm]) (p = 0.003). Features that increased the
      likelihood of ALT/WDL included: patient age over 60 years, maximal lesion
      dimension over 10 cm, location in lower limb, and presence of non-fatty areas, by
      a factor of 2.61-6.25 times. CONCLUSIONS: ALT/WDL and lipoma have overlapping MR
      imaging characteristics. The most reliable imaging discriminators of ALT/WDL were
      size of lesion and lipomatous content, but due to the overlap in the MRI
      appearances of lipoma and ALT/WDL, discrimination should be based on molecular
      pathology rather than imaging.

PMID- 22987248
TI  - Phylogenetic diversity of bacterial endophytes of Panax notoginseng with
      antagonistic characteristics towards pathogens of root-rot disease complex.
AB  - Endophytes play an important role in protection of host plants from infection by
      phytopathogens. Endophytic bacteria were isolated from five different parts
      (root, stem, petiole, leaf and seed) of Panax notoginseng and evaluated for
      antagonistic activity against Fusarium oxysporum, Ralstonia sp. and Meloidogyne
      hapla, three major pathogens associated with root-rot disease complex of P.
      notoginseng. From 1000 endophytic bacterial strains evaluated in vitro, 104
      strains exhibited antagonistic properties against at least one of these three
      pathogens. Phylogenetic analyses of their 16S rRNA gene sequences showed that
      these 104 antagonistic bacteria belong to four clusters: Firmicutes,
      Proteobacteria, Actinobacteria and Bacteroidetes/Chlorobi. Members of the
      Firmicutes, in particular the Bacillus spp., were predominant in all analyzed
      tissues. The root was the main reservoir for antagonistic bacteria. Of the 104
      antagonists, 51 strains showed antagonistic activities to one pathogen only,
      while 43 and 10 displayed the activities towards two and all three pathogens,
      respectively. The most dominant species in all tissues were Bacillus
      amyloliquefaciens subsp. plantarum and Bacillus methylotrophicus, which were
      represented by eight strains with broad antagonistic spectrum to the all three
      test pathogens of root-rot disease complex of P. notoginseng.

PMID- 22987249
TI  - Description of Hymenobacter arizonensis sp. nov. from the southwestern arid lands
      of the United States of America.
AB  - Strain OR362-8(T) was isolated from a biological soil crust sample collected from
      the southwestern arid lands of the United States of America, using BG11-PGY
      medium. Cells of OR362-8(T) were found to be rod shaped; occur singly, as pairs
      and in groups; non-motile; positive for catalase, oxidase, phosphatase and
      gelatinase; hydrolyze starch; contain iso-C(15:0), anteiso-C(15:0), iso-C(15:1)G,
      C(16:1omega5c) and summed feature 3 (C(16:1(omega7c))/iso-C(15:0) 2OH as defined
      by the MIDI system) as the major fatty acids; and MK-7 as the sole respiratory
      quinone. A BLAST sequence similarity search using 16S rRNA gene sequence of OR362
      8(T) identified Hymenobacter as the nearest genus with a similarity of 90.4-96.9
      %. The phylogenetic analyses based on the phenetic methods UPGMA, NJ, ME and DNA
      parsimony resulted in the clustering of OR362-8(T) with Clade 1 Hymenobacter
      species represented by Hymenobacter glaciei, Hymenobacter antarcticus,
      Hymenobacter flocculans, Hymenobacter metalli and Hymenobacter soli with the
      closest being the Hymenobacter glaciei (96.9 % 16S rRNA gene sequence
      similarity). Besides the strong phylogentic affiliation, OR362-8(T) also
      exhibited significant phenotypic and chemotaxonomic differences with the members
      of Clade 1 Hymenobacter spp. More importantly, the DNA G+C content (mol%) of
      OR362-8(T) is very high (70 %) compared to the nearest species identified by
      phylogenetic analysis. Based on the phylogenetic, phenotypic and chemotaxonomic
      characteristics, OR362-8(T) was assigned to a novel species for which we propose
      here the name Hymenobacter arizonensis sp. nov., with OR362-8(T) (=ATCC BAA
      1266(T) = DSM 17860(T) = JCM 13504(T)) as the type strain.

PMID- 22987250
TI  - A global analysis of adaptive evolution of operons in cyanobacteria.
AB  - Operons are an important feature of prokaryotic genomes. Evolution of operons is
      hypothesized to be adaptive and has contributed significantly towards coordinated
      optimization of functions. Two conflicting theories, based on (i) in situ
      formation to achieve co-regulation and (ii) horizontal gene transfer of
      functionally linked gene clusters, are generally considered to explain why and
      how operons have evolved. Furthermore, effects of operon evolution on genomic
      traits such as intergenic spacing, operon size and co-regulation are relatively
      less explored. Based on the conservation level in a set of diverse prokaryotes,
      we categorize the operonic gene pair associations and in turn the operons as
      ancient and recently formed. This allowed us to perform a detailed analysis of
      operonic structure in cyanobacteria, a morphologically and physiologically
      diverse group of photoautotrophs. Clustering based on operon conservation showed
      significant similarity with the 16S rRNA-based phylogeny, which groups the
      cyanobacterial strains into three clades. Clade C, dominated by strains that are
      believed to have undergone genome reduction, shows a larger fraction of operonic
      genes that are tightly packed in larger sized operons. Ancient operons are in
      general larger, more tightly packed, better optimized for co-regulation and part
      of key cellular processes. A sub-clade within Clade B, which includes
      Synechocystis sp. PCC 6803, shows a reverse trend in intergenic spacing. Our
      results suggest that while in situ formation and vertical descent may be a
      dominant mechanism of operon evolution in cyanobacteria, optimization of
      intergenic spacing and co-regulation are part of an ongoing process in the life
      cycle of operons.

PMID- 22987251
TI  - Quantitative approaches for assessing dose-response relationships in genetic
      toxicology studies.
AB  - Genetic toxicology studies are required for the safety assessment of chemicals.
      Data from these studies have historically been interpreted in a qualitative,
      dichotomous "yes" or "no" manner without analysis of dose-response relationships.
      This article is based upon the work of an international multi-sector group that
      examined how quantitative dose-response relationships for in vitro and in vivo
      genetic toxicology data might be used to improve human risk assessment. The group
      examined three quantitative approaches for analyzing dose-response curves and
      deriving point-of-departure (POD) metrics (i.e., the no-observed-genotoxic-effect
      level (NOGEL), the threshold effect level (Td), and the benchmark dose (BMD)),
      using data for the induction of micronuclei and gene mutations by methyl
      methanesulfonate or ethyl methanesulfonate in vitro and in vivo. These results
      suggest that the POD descriptors obtained using the different approaches are
      within the same order of magnitude, with more variability observed for the in
      vivo assays. The different approaches were found to be complementary as each has
      advantages and limitations. The results further indicate that the lower
      confidence limit of a benchmark response rate of 10% (BMDL(10) ) could be
      considered a satisfactory POD when analyzing genotoxicity data using the BMD
      approach. The models described permit the identification of POD values that could
      be combined with mode of action analysis to determine whether exposure(s) below a
      particular level constitutes a significant human risk. Subsequent analyses will
      expand the number of substances and endpoints investigated, and continue to
      evaluate the utility of quantitative approaches for analysis of genetic toxicity
      dose-response data.

PMID- 22987252
TI  - Flow-through fibula flap using soleus branch as distal runoff: a case report.
AB  - The flow-through fibula flap utilizing the soleus branch as a distal runoff has
      not yet been reported. We herein present a patient with left tibial adamantimoma
      in whom wide resection of the tumor resulted in a segmental tibial defect 22 cm
      in length. The defect was successfully reconstructed with a flow-through free
      fibula osteocutaneous flap using the soleus branch of the peroneal artery as a
      distal runoff. The short T-segment of the peroneal artery was interposed to the
      transected posterior tibial artery. The soleus branch has a constant anatomy and
      a larger diameter than the distal stump of the peroneal artery. Short interposed
      flow-through anastomosis to the major vessels is much easier and more reliable
      than the conventional methods. We believe that our method represents a versatile
      option for vascularized fibula bone grafting for extremity reconstruction.

PMID- 22987253
TI  - Platelet response as the basis for approval in chronic immune (idiopathic)
      thrombocytopenic purpura (ITP): a regulatory perspective.

PMID- 22987254
TI  - ZnS nanocrystal cytotoxicity is influenced by capping agent chemical structure
      and duration of time in suspension.
AB  - As a result of their characteristic physical and optical properties, including
      their size, intense fluorescence, broad excitation, narrow emission and
      resistance to photobleaching, semiconductor nanocrystals are potentially useful
      for a variety of biological applications including molecular imaging, live-cell
      labeling, photodynamic therapy and targeted drug delivery. In this study, zinc
      sulfide (ZnS) semiconductor nanocrystals were synthesized in the 3 to 4 nm size
      range with selected capping agents intended to protect the nanocrystal core and
      increase its biological compatibility. We show that the biocompatibility of ZnS
      nanocrystals with primary murine splenocytes is influenced by the chemical
      structure of the outer capping agent on the nanocrystal. Additionally, the
      cytotoxicity of ZnS nanocrystals increases markedly as a function of time spent
      in suspension in phosphate-buffered saline (PBS). These data suggest that the
      potential therapeutic and/or biological use of ZnS nanocrystals is inherently
      dependent upon the proper choice of capping agent, as well as the conditions of
      nanocrystal preparation and storage.

PMID- 22987255
TI  - Resuming anticoagulation in the first week following gastrointestinal tract
      hemorrhage: should we adopt a 4-day rule?

PMID- 22987256
TI  - Doppler of the uterine arteries combined with endometrial thickness correlate
      well with the degree of pituitary suppression in women treated with long-acting
      GnRH agonists.
AB  - PURPOSE: The aim of this study was to evaluate the use of Doppler velocimetry of
      the uterine arteries and its association to endometrial thickness as a method to
      confirm pituitary suppression after administration of gonadotropin-releasing
      hormone analogues in assisted reproduction treatment cycles. METHODS: A total of
      70 patients using gonadotropin-releasing hormone analogues for pituitary
      suppression for in vitro fertilization treatment were studied. To confirm down
      regulation, serum estradiol levels and endometrial thickness were evaluated 10
      days after gonadotropin-releasing hormone analogues administration. When
      estradiol was <30 pg/ml and endometrial thickness was <3 mm, pituitary
      suppression was confirmed. Doppler velocimetric measurements were performed at
      the same day to study the pulsatility index of the uterine arteries, until
      pituitary suppression was confirmed. RESULTS: All 70 patients had normal ovarian
      morphology. For the patients who had estradiol levels <=30 pg/ml, the mean
      pulsatility index of the uterine arteries was 2.95 +/- 0.79 and for those who had
      levels >30 pg/ml the mean PI was 2.22 +/- 0.8 (p = 0.005). For the patients who
      had endometrial thickness <=5 mm the mean PI was 2.86 +/- 0.82 and for those with
      endometrial thickness >5 mm the mean PI was 2.17 +/- 0.79 (p = 0.004). Using a
      cut-off point of 2.51 for the pulsatility index, to compare to estradiol levels,
      we observed a sensitivity of 72.7 % and specificity of 71 %. The combination of
      Doppler velocimetric and endometrial thickness showed a sensitivity of 94 % and
      specificity of 82.3 %. CONCLUSIONS: Doppler velocimetric analysis of the uterine
      arteries can be an important tool in the diagnosis of the down-regulation after
      the use of gonadotropin-releasing hormone analogues and might help simplify
      assisted reproduction programmes.

PMID- 22987257
TI  - Effects of low molecular weight heparins and unfractionated heparin on viability
      of human umbilical vein endothelial cells.
AB  - AIM: The aim of this study was to investigate the effects of bemiparin,
      nadroparin, enoxaparin, and heparin on viability of human umbilical vein
      endothelial cells (HUVEC). METHODS: Cultivation of HUVEC was performed in an
      incubator having 5 % CO(2) at 37  degrees C and with predefined supplemented
      medium, until cell monolayers attained confluence which occurred after 7 days.
      The assays were performed in the exponential growth phase of the cells. The cell
      viability was assessed using the cleavage of tetrazolium salts added to the
      culture medium. Heparin sodium, enoxaparin sodium, bemiparin sodium, and
      nadroparin calcium with concentrations of 100, 10, and 1 IU/100 MUL were used for
      the proliferation assay in which cells were incubated for 24, 48, and 72 h with
      these drugs. The experiments were conducted in four replicates. RESULTS: Among
      the study drugs with maximal concentration used in the experiments (100 IU/100
      MUL), heparin was found to be associated with the lowest viability score in 24
      and 48 h, while bemiparin showed the lowest at 72 h. Bemiparin 100 IU/100 MUL was
      significantly associated with lower viability score than that of bemiparin 10
      IU/100 MUL and bemiparin 1 IU/100 MUL at every time interval. Among gradual
      concentrations of enoxaparin, however, concentration of 1 IU/100 MUL was
      associated with the lowest viability scores at every time point. Heparin 1 IU/100
      MUL, nadroparin 100 IU/100 MUL, and enoxaparin 100 IU/100 MUL groups had the
      highest viability score after 72 h of incubation. CONCLUSION(S): Among low
      molecular weight heparins (LMWHs), 100 IU/100 MUL concentration of bemiparin was
      associated with a more pronounced effect on reducing viability of HUVEC after 72
      h of incubation, while nadroparin 100 IU/100 MUL and enoxaparin 100 IU/100 MUL
      showed the least effects. LMWHs differ both from each other and heparin with
      respect to their effects on cellular viability of HUVEC in dose- and time
      dependent manner.

PMID- 22987258
TI  - Minimal invasive approaches for large ovarian cysts: a careful choice.

PMID- 22987259
TI  - Peeking into personality test answers: inter- and intraindividual variety in item
      interpretations.
AB  - Personality research of today applies basically inventories having neither
      unambiguously interpretable items nor responses. The substantive process of
      generating the test answer is rarely investigated and thus the possible field of
      meanings, out of which the answer is created, remains hidden. In order to
      investigate the possible array of spontaneous answers to personality test items,
      a situative open-ended personality inventory was developed to determine
      individuals' ways of interpreting personality test items and relevant personality
      descriptions for individuals. The children's sample (N = 704 of 10-13 year olds)
      answered five free-response contextualized personality test questions, each
      related to one of the Five Factor Model personality dimensions. It was revealed
      that there is no universal interpretation of an item. First, different children's
      answers to same question described different personality dimensions - substantial
      number of the respondents' answers did not reflect the personality domain assumed
      in an item. So there are several ways to interpret test questions; answers may
      refer to different personality dimensions and not necessarily the one assumed by
      the researcher. Second, a number of children mentioned more than one personality
      trait for one item, indicating that even within one person there may be several
      relevant interpretations of the same item. Considering personality traits as
      occurring one by one and mutually exclusively during personality test answering
      may be artificial; in reality trait combinations may reflect actual reaction. In
      sum, the results suggest there is no single predictable interpretational
      trajectory in meaning construction process if semiotically mediated constructs,
      e.g., personality reflection, are assessed.

PMID- 22987261
TI  - [Matematical modeling of antibiotic resistance: perspectives from a meta
      analysys].
AB  - The antibiotic resistance is one of the greatest challenges of the international
      health community. The study of antibiotic resistance must be a multidisciplinary
      task and, in this sense, the main goal of this work is to analyze the role that
      Mathematical Modeling can play in this scenario. A qualitative and cuantitative
      analysis of the works published in the scientific literature is done by means of
      a search in the most important databases: MEDLINE, SCOPUS and ISI Web of Science.
      Consequently, there are few papers related to our topic but the existing works
      have been published in high-quality and impact international journals. Moreover,
      we can state that mathematical models are a very important and useful tool to
      analyze and study both the treatments protocols for resistance prevention and the
      assesment of control strategies in hospital environtment, or the prediction of
      the evolution of diseases due to resistant strains.

PMID- 22987262
TI  - [Investigation of antimicrobial resistance to Enterococcus faecium].
AB  - We performed a antibiotic resistance study on Enterococcus faecium isolated from
      intrahospitalary and extrahospitalary samples between 2004 and 2010. Three
      different samples were studied; urine, blood and wound swabs, considering a
      strain per patient. We included in the study a global amount of 637 E. faecium
      isolares. We employed semiautomatic system WIDER I for identification and
      sensitivity testing. We considered susceptibility and resistance criteria
      recommended by MENSURA group. We found a susceptibility rate of 48.05% to
      betalactams, 100% to linezolid, and 99.46% to vancomycin. The resistance to
      aminoglycosides ranged between 41.41 and 73.55%. We obtained 6 isolates resistant
      to vancomycin one of them from an extrahospitalary strain and five from
      intrahospitalary strains. It seems that vancomycin resistance should be
      controlled.

PMID- 22987263
TI  - [Antimicrobial resistance of the most frequently isolated microorganisms in the
      Hospital General La Mancha Centro between June 2009 and May 2010].
AB  - INTRODUCTION: During the last two decades an increased incidence of infections
      caused by multiresistant bacteria has been observed. The spread of these
      microorganisms in the hospital is a major therapeutic and epidemiological
      problem. The aim of this study was to determine local resistance patterns of
      microorganisms causative of multirresistant infections in patients admitted to
      our hospital. METHODS: A retrospective study was designed, including
      Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeruginosa and Acinetobacter baumannii strains isolated from clinical and
      surveillance samples of patients admitted to the Hospital General La Mancha
      Centro, between June 2009 and May 2010. RESULTS: The rate of S. aureus isolates
      resistant to oxacillin was 50%, with 0% resistance to vancomycin. The percentage
      of resistance to 3rd generation cephalosporins in E. coli and K. pneumoniae was
      17 and 19%, respectively; the ESBL-production in enterobacterial strains was 15
      and 19%, respectively, and the quinolone resistance was 41 and 28%, respectively.
      The resistance of P. aeruginosa to ceftazidime and imipenem was 30 and 40%,
      respectively. Most strains of A. baumannii studied came from a single multidrug
      resistant clone, endemic in the ICU of our hospital. CONCLUSIONS: Of particular
      concern is the high rate of MRSA, E. coli and K. pneumoniae ESBL producers and
      resistant to fluoroquinolones as well as P. aeruginosa multiresistant. A.
      baumannii isolates belong mainly to endemic multidrug-resistant clone from the
      ICU.

PMID- 22987264
TI  - [Evaluation of the variability in the susceptibility of Acinetobacter baumannii
      to tigecycline in the same medium with two methods of quantitative diffusion
      different commercial].
AB  - INTRODUCTION: Tigecycline may be a therapeutic alternative for the control of
      multidrug-resistant Acinetobacter baumannii, although there is no consensus on
      the cutoffs or susceptibility to the variability of the minimum inhibitory
      concentration (MIC) according to the culture medium and strips for the
      antibiogram against this microorganism by quantitative diffusion method.
      Therefore, the objective was to verify this variability and propose epsilometer
      test strip that more closely resemble to the standard method. MATERIAL AND
      METHODS: 38 strains of A. baumannii were selected and evaluated their
      susceptibility to tigecycline with two different commercial strips (E-TEST and
      Liofilchem). MICs were compared with those obtained by the standard technique of
      microdilution broth. RESULTS: MICs obtained by the Liofilchem strip were more
      similar to standard method than those obtained by E-TEST strips. CONCLUSION: In
      the two studied strips, higher MICs to those obtained by the standard method were
      observed leading to false-positive tigecicline resistance in many cases. However,
      the Liofilchem strip showed the results more closely resemble to the standard
      method.

PMID- 22987265
TI  - Long-term outcome of acute prosthetic joint infections due to gram-negative
      bacilli treated with retention of prosthesis.
AB  - OBJECTIVE: To update the clinical information of the 47 patients with a
      prosthetic joint infection due to Gram-negative bacilli included in a previous
      study and to reassess the predictors of failure after a longer follow-up.
      METHODS: Using the electronic files of our hospital, all the information
      regarding readmissions to the hospital, new surgical procedures and the reason
      for the new surgery (infection, aseptic loosening), and the last visit in the
      hospital were registered. The medical chart of the 35 patients that were
      considered in remission in the previous publication was reviewed. RESULTS: In 30
      patients no clinical evidence of failure was detected and no additional surgery
      on the previously infected prosthesis was necessary and they were considered in
      long-term remission. In 5 cases a late complication was identified. One case had
      a reinfection due to coagulase-negative staphylococci after 22 months from the
      open debridement and required a 2-stage revision surgery. The other 4 cases
      developed an aseptic loosening and it was necessary to perform a 1-stage
      exchange. Receiving a fluoroquinolone when all the Gram-negatives involved in the
      infection were susceptible to fluoroquinolones was the only factor associated
      with remission in the univariate analysis (p=0.002). CONCLUSION: After a long
      term follow-up, our results support the importance of using fluoroquinolones in
      acute PJI due to Gram-negative bacilli.

PMID- 22987266
TI  - [Coagulase-negative Staphylococcus bacteraemia: prognosis factors and influence
      of antibiotic treatment].
AB  - INTRODUCTION: Coagulase-negative staphylococci (CNS) are the most frequent
      isolated microorganism in blood cultures; mortality has been associated to
      severity and to adequacy of empirical treatment but the relevance of the latter
      is not clearly recognised. The aims of the study were to analyze clinical and
      microbiological factors related to mortality in patients with CNS bacteraemia and
      the influence of empirical treatment in prognosis. PATIENTS AND METHODS: A
      prospective cohort study of patients with CNS bacteraemia was performed (January
      to June 2010) at a university-affiliated hospital; a determination of clinical
      significance was made and true bacteraemia was defined according to CDC criteria.
      We analysed epidemiological, clinical and microbiological variables related to
      mortality. RESULTS: A total of 269 cases were included (97 were considered true
      bacteraemia); 92% survived and mortality was 8% (1.6% CNS bacteraemia related
      mortality). Staphylococcus epidermidis was the most frequent isolated species; 93
      patients were included in the related mortality study of patients with true
      bacteraemia. Factors associated to mortality in the bivariate analysis (p<0.05)
      were: Winton score I-III, presence of pacemakers, sepsis or infective
      endocarditis and persistent bacteraemia. Adequate empirical treatment was not
      associated to survival. CONCLUSIONS: Severity at onset, the development of septic
      complications and having a pacemaker are associated to mortality in patients with
      CNS bacteraemia; in our cohort, inadequate empirical treatment is not related to
      mortality.

PMID- 22987268
TI  - [Meningitis due to Salmonella enterica].

PMID- 22987269
TI  - [Septic arthritis of the knee by Stenotrophomonas maltophilia].

PMID- 22987270
TI  - [Leptotrichia goodfellowii wound infection after a dog bite].

PMID- 22987271
TI  - [Strain of Escherichia coli resistant to broad-spectrum cephalosporin and
      amoxicillin/clavulanic acid].

PMID- 22987272
TI  - Comment on: Predictive factors for pneumonia in new pandemic H1N1 influenza.

PMID- 22987267
TI  - Impact of liposomal amphotericin B on renal function in critically ill patients
      with renal function impairment.
AB  - OBJECTIVE: To assess the tolerability of liposomal amphotericin B (L-AmB) in
      critically ill patients with elevated serum creatinine concentrations (Cr) (> 1.5
      mg/dL) at starting L-AmB therapy. METHODS: Retrospective, multicenter,
      comparative study of two cohorts of critically ill patients treated with L-AmB
      during 3 or more days, the difference between them was the level of Cr at the
      beginning of treatment. A cutoff value of Cr of 1.5 mg/dL was established.
      Patients undergoing extrarenal depuration procedures before or 48 hours after
      starting L-AmB were excluded. The primary endpoint was the difference between Cr
      values at the end of treatment as compared with Cr at starting L-AmB. Secondary
      endpoints were treatment-related withdrawals, need of extrarenal depuration
      techniques, and treatment-related severe adverse events. Demographic data,
      underlying illness, indication of L-AmB therapy, concomitant risk factors of
      nephrotoxicity, and vital status at ICU and hospital discharge were recorded.
      RESULTS: A total of 122 patients admitted to 26 ICUs (16 with Cr > 1.5 g/dL; 106
      with normal Cr levels) were recruited. Main reasons for the use of L-AmB in both
      groups were the broad spectrum of the drug and the presence of hemodynamic
      instability. L-AmB was administered as first-line treatment in 68.8% of patients
      with elevated Cr and in 52.8% with normal Cr. The APACHE II score on ICU
      admission was 25 in patients with elevated Cr and 17 in those with normal Cr
      values (p < 0.001). Duration of treatment with L-AmB was 16 and 12 days in
      patients with elevate and normal Cr values, respectively, with a mean dose of 3.5
      vs 3.9 mg/kg/day. The use of concomitant nephrotoxic drugs, mortality rate, and
      ICU and hospital length of stay were similar in both cohorts. In patients with
      renal function impairment at the initiation of L-AmB treatment, an absolute
      decrease of Cf-Ci of 1.08 mg/dL was observed (P < 0.001). A decrease of Cr levels
      to normal limits was observed in 50% of the patients; in 37.5% of patients there
      was a decrease but normal levels were not achieved, whereas a Cr increased
      occurred in only one (6.25%) patient. None of the patients required withdrawal of
      L-AmB or use of extrarenal depuration procedures. Treatment-related severe
      adverse events were not reported. CONCLUSIONS: In critically ill patients with
      impaired renal function, the impact of L-AmB on renal function was minimal. L-AmB
      can be used for the treatment of fungal infections in critically ill patients
      independently of renal function at the initiation of treatment.

PMID- 22987273
TI  - [Consensus document on vaccination against influenza in health care workers].
AB  - Health care workers (HCW) are included each year among risk groups for
      vaccination against influenza. However, vaccination coverage among this group in
      our country is very low, not exceeding 25%. Convinced that one of the best tools
      to increase this coverage among professionals in our country are the scientific
      evidence, 19 scientific societies and associations professionals bringing
      together health professionals more directly related to influenza as an health
      problem, and the General Nursing Council, met to discuss and develop this
      consensus document in order to inform HCW about the appropriateness of their
      vaccination against influenza and the benefits that flow from it for themselves,
      for their patients and for the rest of the population. This recommendation is
      based on 3 pillars: argument of necessity, ethics and exemplary.

PMID- 22987274
TI  - A classic presentation of an uncommon leukemia.

PMID- 22987275
TI  - Diagnostic and prognostic significance of miRNA signatures in tissues and plasma
      of endometrioid endometrial carcinoma patients.
AB  - The aim of our study was to define tissue and plasma miRNA signatures, which
      could potentially serve as diagnostic and prognostic markers in endometrioid
      endometrial cancer (EEC) and to investigate miRNA profiles in regard to
      clinicopathological characteristics. Tissue and plasma samples were collected
      from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs
      and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR
      validation in 104 patients. Expression of 16 miRNAs was analyzed in 48 plasma
      samples. Microarray study revealed regulation of 21 miRNAs in EEC tissues
      comparing to normal endometrium. Altered expression of 17 miRNAs was confirmed by
      qPCR performed in 104 tissue samples. Seven miRNAs were upregulated and two were
      downregulated in EEC plasma samples. Expression of a number of miRNAs was
      associated with International Federation of Gynecology and Obstetrics stage,
      grade, relapse and nodal metastases. Two miRNA signatures: miR-92a/miR-410 and
      miR-92a/miR-205/miR-410 classified tumor tissues with higher accuracy in
      comparison to single miRNAs (AUC: 0.977, 95% CI: 0.927-0.996 and 0.984, 95% CI:
      0.938-0.999, respectively). miRNA signature composed of miR-205 and miR-200a
      predicted relapse with AUC of 0.854 (95% CI: 0.691-0.951). Tissue miRNA
      signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR
      429, HR: 2.98) and progression-free survival (miR-1228/miR-429, HR: 2.453).
      Plasma miRNA signatures: miR-9/miR-1228 and miR-9/miR-92a, classified EEC plasma
      samples with high accuracy yielding AUCs of 0.909 (95% CI: 0.789-973) and 0.913
      (95% CI: 0.794-0.976), respectively. We conclude that miRNA signatures hold a
      great promise to become noninvasive biomarkers for early EEC detection and
      prognosis.

PMID- 22987276
TI  - DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II
      poison-induced chromosome aberrant cells.
AB  - The role of DNA double strand break (DSB) repair pathways, non-homologous end
      joining (NHEJ), and homologous recombination (HR) was evaluated to prevent the
      chromosome instability induced by the topoisomerase II (Top2) poisons,
      idarubicin, and etoposide in Chinese hamster cell lines. XR-C1 (DNA-PKcs
      deficient) and V-C8 (BRCA2 deficient) showed higher sensitivity to increased
      concentrations of Top2 poisons compared with their normal counterparts, CHO9 and
      V79. Both proficient and deficient cells exhibited a marked DSB induction in all
      phases of the cell cycle. Additionally, deficient cells showed persistent DNA
      damage 24 hr post-treatment. Chromosomal aberrations increased in the first
      mitosis following Top2 poison-treatments in G1 or G2 in proficient and deficient
      cells. CHO9 and V79 demonstrated chromosome and chromatid exchanges following
      treatments in G1 and G2 phases, respectively. Deficient cells showed high
      frequencies of chromatid exchanges following treatments in G1 and G2.
      Simultaneously, we analyzed the micronuclei (MN) induction in interphase cells
      after treatments in G1, S, or G2 of the previous cell cycle. Both Top2 poisons
      induced an important increase in MN in CHO9, V79, and V-C8 cells. XR-C1 exhibited
      an increased MN frequency when cells were treated in G1 phase but not in S or G2.
      This MN reduction was due to a cell accumulation at G2/M and death in G2-treated
      cells. Our data suggest that NHEJ and HR operate differentially throughout the
      cell cycle to protect from Top2 poison-induced chromosome instability, and that
      DNA-PKcs-dependent NHEJ pathway allows the survival of chromosome damaged cells
      during S/G2 to the next interphase.

PMID- 22987277
TI  - Surgical treatment of esophageal perforations: the importance of a primary
      repair.
AB  - PURPOSE: The aim of the current study was to evaluate the outcome after primary
      repair in comparison to other surgical treatments and the advantage of
      reinforcing the sutures with an absorbable polyglactin 910 prosthesis. METHODS:
      All esophageal perforations surgically managed in this institution from January
      1985 through April 2009 (n = 40) were retrospectively analyzed. Patients that
      underwent surgery with primary sutures (group A, n = 24) were compared with
      patients that received other surgical procedures (group B, n = 16). The time to
      initiate treatment (within or after the first 24 h) and if the suture was
      reinforced with a polyglactin 910 mesh were also analyzed in group A patients.
      RESULTS: The outcome was more favorable in group A than group B in terms of time
      in the intensive care unit (p = 0.005), and rate of reoperation (p = 0.005).
      There was no difference in the outcome after the primary suture with or without
      mesh reinforcement, although the rate of fistulization was lower in patients with
      a mesh (17 vs. 50 %, p = 0.19). CONCLUSIONS: Primary repair has a better outcome
      than other surgical treatment, even when performed more than 24 h after symptom
      onset, but not later than 48 h. Reinforcing the sutures with an absorbable
      polyglactin 910 mesh therefore seems to improve the outcome.

PMID- 22987278
TI  - Endovascular management of axillosubclavian artery injuries: report of three
      cases.
AB  - Open surgical repair of axillosubclavian artery injuries is technically demanding
      and associated with significant morbidity and mortality. Endovascular
      intervention has emerged as a valuable alternative to open surgical repair. This
      report presents three cases with axillosubclavian artery injuries managed with
      endovascular intervention. All three cases had a pseudoaneurysm of the
      axillosubclavian artery with one case associated with an arteriovenous fistula.
      They were successfully treated with endovascular stenting and balloon
      angioplasty. There were no observed acute complications. No complications or
      recurrence have occurred, with a mean follow-up of 26 months. Endovascular
      intervention for axillosubclavian artery injuries is less invasive, safe and
      effective; however, data concerning the long-term effects and complications
      associated with this technique are lacking.

PMID- 22987280
TI  - Supramolecular assembly of diplatinum species through weak Pt(II)???Pt(II)
      intermolecular interactions: a combined experimental and computational study.
AB  - The present study elucidates the factors that govern the spontaneous self
      assembly of a family of dimetal [Pt(2)L(4)] (L=dithiocarboxylato ligand)
      complexes. Experimental data show that variables such as temperature,
      concentration, solvent and the nature of the ligand L have a critical effect on
      the reversible self-assembly of supramolecular [Pt(2)L(4)](n) entities. In
      solution, new UV/Vis spectroscopic features emerge at low temperatures and/or
      high concentrations, which are attributed to the formation of oligomeric
      [Pt(2)L(4)](n) species. The description of intermolecular Pt???Pt interactions,
      the main driving force for the association, was addressed from a computational
      perspective. The contributions from intermolecular Pt???S and S???S interactions
      to these supramolecular assemblies were found to be repulsive. Experimental
      UV/Vis data have been interpreted by means of computational spectroscopy.

PMID- 22987279
TI  - Giant Krukenberg tumor from a perforated gastric cancer that was successfully
      removed after multidisciplinary therapy: report of a case.
AB  - A 46-year-old female underwent total gastrectomy with a combined resection of the
      pancreatic tail, spleen, and lateral segment of the liver surgery after
      conservative medical management for a perforated advanced gastric cancer. The
      histological findings showed poorly differentiated adenocarcinoma, and the tumor
      was Stage IIIC. S-1 and "Kampo-Juzen-taiho-to" were administered as postoperative
      adjuvant chemo-immunotherapy. A Krukenberg tumor was identified 4 years later.
      The histological findings strongly suggested the presence of peritoneal
      dissemination, and S-1-based combined chemotherapies using key drugs such as
      CDDP, CPT-11, and taxane with the biochemical response modifier "Lentinan" was
      administered. However, the Krukenberg tumor rapidly increased in size after 4
      years and she complained of abdominal distension. Therefore, it was removed with
      neither difficulties nor apparent recurrent disease, which was thought to be due
      to the S-1-based combined chemotherapy and the immunological agents are likely to
      have contributed to her long survival and good quality of life. 

PMID- 22987281
TI  - Quality of life instruments for skull base pathology: systematic review and
      methodologic appraisal.
AB  - BACKGROUND: Several quality of life (QOL) instruments exist for skull base
      pathology, however, there have been no attempts to appraise and systematically
      review these instruments. METHODS: We systematically reviewed MEDLINE, EMBASE,
      Central, AMED, Health and Psychosocial Instruments, and PsychoInfo for anterior
      or central skull base QOL instruments to January 2010. We queried experts,
      bibliographies, and meeting proceedings from the North American Skull Base
      Society from 2005 to 2009. Included instruments were evaluated for instrument
      characteristics, item generation and reduction, field testing, and measurement
      properties using predefined criteria. RESULTS: We identified 9 QOL instruments: 7
      measuring QOL for pituitary pathology, 1 for midface pathology, and 1 for
      anterior skull base pathology. Eight of the 9 instruments have had some
      psychometric testing. None demonstrated all of the predefined psychometric
      properties. CONCLUSIONS: There are several QOL instruments for patients with
      skull base pathology. None of these instruments met all predefined requirements,
      and further instrument development is needed.

PMID- 22987282
TI  - An exact model for predicting tablet and blend content uniformity based on the
      theory of fluctuations in mixtures.
AB  - Content uniformity (CU) of tablets is a critical property that needs to be well
      controlled in pharmaceutical products. Methods that predict the CU accurately can
      greatly help in reducing the development efforts. This article presents a
      statistical mechanical framework for predicting CU based on first principles at
      the molecular level. The tablet is modeled as an open system that can be treated
      as a grand canonical ensemble to calculate fluctuations in the number of granules
      and thus the CU. Exact analytical solutions to hard sphere mixture systems are
      applied to derive an expression for the CU and elucidate the different factors
      that impact CU. The model was tested against literature data and a large set of
      tablet formulations specifically made and analyzed for CU using a model active
      pharmaceutical ingredient. The formulations covered the effect of granule size,
      percentage loading, and tablet weight on the CU. The model is able to predict the
      mean experimental coefficient of variation (CV) with good success and captures
      all the elements that impact the CU. The predictions of the model serve as a
      theoretical lower limit for the mean CV (for infinite batches or tablets) that
      can be expected during manufacturing assuming the best processing conditions.

PMID- 22987283
TI  - DC-gated high resolution three-dimensional lung imaging during free-breathing.
AB  - PURPOSE: To use the acquisition of the k-space center signal (DC signal)
      implemented into a Cartesian three-dimensional (3D) FLASH sequence for
      retrospective respiratory self-gating and, thus, for the examination of the whole
      human lung in high spatial resolution during free breathing. MATERIALS AND
      METHODS: Volunteer as well as patient measurements were performed under free
      breathing conditions. The DC signal is acquired after the actual image data
      acquisition within each excitation of a 3D FLASH sequence. The DC signal is then
      used to track respiratory motion for retrospective respiratory gating. RESULTS:
      It is shown that the acquisition of the DC signal after the imaging module can be
      used in a 3D FLASH sequence to extract respiratory motion information for
      retrospective respiratory self-gating and allows for shorter echo times (TE) and
      therefore increased lung parenchyma SNR. CONCLUSION: The acquisition of the DC
      signal after image signal acquisition allows successful retrospective gating,
      enabling the reconstruction of high resolution images of the whole human lung
      under free breathing conditions.

PMID- 22987284
TI  - Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T
      cells provides the immunological basis for flucloxacillin-induced liver injury.
AB  - The role of the adaptive immune system in adverse drug reactions that target the
      liver has not been defined. For flucloxacillin, a delay in the reaction onset and
      identification of human leukocyte antigen (HLA)-B*57:01 as a susceptibility
      factor are indicative of an immune pathogenesis. Thus, we characterize
      flucloxacillin-responsive CD4+ and CD8+ T cells from patients with liver injury
      and show that naive CD45RA+CD8+ T cells from volunteers expressing HLA-B*57:01
      are activated with flucloxacillin when dendritic cells present the drug antigen.
      T-cell clones expressing CCR4 and CCR9 migrated toward CCL17 and CCL 25, and
      secreted interferon-gamma (IFN-gamma), T helper (Th)2 cytokines, perforin,
      granzyme B, and FasL following drug stimulation. Flucloxacillin bound covalently
      to selective lysine residues on albumin in a time-dependent manner and the level
      of binding correlated directly with the stimulation of clones. Activation of CD8+
      clones with flucloxacillin was processing-dependent and restricted by HLA-B*57:01
      and the closely related HLA-B*58:01. Clones displayed additional reactivity
      against beta-lactam antibiotics including oxacillin, cloxacillin, and
      dicloxacillin, but not abacavir or nitroso sulfamethoxazole. CONCLUSION: This
      work defines the immune basis for flucloxacillin-induced liver injury and links
      the genetic association to the iatrogenic disease.

PMID- 22987285
TI  - Enantioselective formal total syntheses of didehydrostemofoline and
      isodidehydrostemofoline through a catalytic dipolar cycloaddition cascade.
AB  - Sweet to the core: Enantioselective formal total syntheses of the title compounds
      were accomplished in 24 steps from 2-deoxy-D-ribose. The synthesis features a
      novel cascade of reactions culminating in an intramolecular dipolar cycloaddition
      to form the tricyclic core of the stemofoline alkaloids from an acyclic diazo
      imine intermediate.

PMID- 22987286
TI  - Effects of feeding sweet potato (Ipomoea batatas) vines as a supplement on feed
      intake, growth performance, digestibility and carcass characteristics of Sidama
      goats fed a basal diet of natural grass hay.
AB  - The objective of this study was to investigate the effects of substituting sweet
      potato [Ipomoea batatas (L) Lam] vines for concentrate on growth performance,
      digestibility, and carcass characteristics. Thirty yearling bucks (15.3 +/- 1.64
      kg) were assigned into six treatments in a randomized complete block design:
      natural grass hay alone (T1) or supplemented with 100 % sweet potato vines (SPV)
      (T2), 65 % SPV + 35 % concentrate (T3), 35 % SPV + 65 % concentrate (T4), and 100
      % concentrate (T5) on dry matter (DM) basis. Supplemented goats (T2, T3, T4, and
      T5) consumed higher (p < 0.001) total DM (553, 567, 505, and 515 g/day),
      respectively, when compared to the nonsupplemented (T1) goats (349 g/day). The
      crude protein (CP) intake (32.0, 48.6, 54.7, and 69.2 g/day) increased with
      increasing levels of the concentrate in the diet for T2, T3, T4, and T5,
      respectively. The DM digestibility in T2, T3, T4, and T5, respectively, was
      higher (P < 0.01) (0.69, 0.72, 0.72, and 0.74) than in T1 (0.56). Apparent
      digestibility of CP was observed to be higher (P < 0.001) in T3, T4, T5 (0.78,
      0.83, and 0.88) when compared to the bucks in T2 (0.60). Higher (P < 0.001) daily
      weight gain (31.2, 46.4, 48.6, and 47.6 g/day) were recorded for T2, T3, T4, and
      T5, respectively, whereas the nonsupplemented goats lost weight (-19.5 g/day).
      Slaughter weight, empty body weight, hot carcass weight, dressing percentage, rib
      eye muscle area, and total edible offals were higher (P < 0.05) in supplemented
      goats compared with nonsupplemented ones. Therefore, it could be concluded that
      sweet potato vine can replace the conventional concentrate and could be fed with
      poor quality hay to prevent body weight loss of animal in the absence of other
      feed supplements.

PMID- 22987287
TI  - Brief report: Misinterpretation of coculture differentiation experiments by
      unintended labeling of cardiomyocytes through secondary transduction: delusions
      and solutions.
AB  - Cardiomyogenic differentiation of stem cells can be accomplished by coculture
      with cardiomyocytes (CMCs). To facilitate their identification, stem cells are
      often labeled through viral transduction with a fluorescent protein. A second
      marker to distinguish stem cell-derived CMCs from native CMCs is rarely used.
      This study aimed to investigate the occurrence of secondary transduction of
      unlabeled neonatal rat (nr) CMCs after coculture with human cells that had been
      transduced 0, 7, or 14 days earlier with a vesicular stomatitis virus (VSV) G
      protein-pseudotyped lentiviral vector (LV) encoding enhanced green fluorescent
      protein (GFP). To reduce secondary LV transfer, GFP-labeled cells were incubated
      with non-heat-inactivated human serum (NHI) or with VSV-neutralizing rabbit serum
      (alphaVSV). Heat-inactivated human serum and normal rabbit serum were used as
      controls. Immunostaining showed substantial GFP gene transfer to nrCMCs in
      cocultures started at the day of transduction indicated by the presence of GFP
      positive/human lamin A/C-negative nrCMCs. The extent of secondary transduction
      was significantly reduced in cocultures initiated 7 days after GFP transduction,
      while it was completely abolished when human cells were added to nrCMCs 14 days
      post-transduction. Both NHI and alphaVSV significantly reduced the occurrence of
      secondary transduction compared to their controls. However, under all
      circumstances, GFP-labeled human cells had to be passaged for 14 days prior to
      coculture initiation to prevent any horizontal GFP gene transfer to the nrCMCs.
      This study emphasizes that differentiation experiments involving the use of viral
      vector-marked donor cells should be interpreted with caution and describes
      measures to reduce/prevent secondary transduction.

PMID- 22987289
TI  - Adverse reactions in patients with B-cell lymphomas during combined treatment
      with rituximab: In vitro evaluation of rituximab hypersensitivity by basophil
      activation test.

PMID- 22987288
TI  - Donor polymorphisms of toll-like receptor 4 associated with graft failure in
      liver transplant recipients.
AB  - There have been many reports showing significant associations between recipient
      genetic variants and allograft outcomes, including acute rejection and graft
      failure, but less is known about the contribution of the donor genotype. We
      analyzed 37 single-nucleotide polymorphisms (SNPs) within the toll-like receptor
      4 (TLR4) gene from deceased donor liver allografts transplanted into 738
      recipients to determine their effects on liver graft failure (LGF). Two SNPs
      exhibited a significant association with LGF after adjustments for donor race and
      recipient race and corrections for multiple test comparisons: rs11536865 [hazard
      ratio (HR) = 2.5, P = 0.0003] and rs5030717 (HR = 1.67, P = 0.0008). An
      additional SNP, rs913930, exhibited a significant association in Caucasian donors
      (HR = 1.62, P = 0.0006), and 2 SNPs exhibited a suggestive association in African
      American donors: rs11536865 (HR = 2.45, P = 0.002) and rs5030717 (HR = 2.32, P =
      0.002). Additionally, the liver donor risk index (HR = 2.56, 95% confidence
      interval = 1.54-4.26, P = 0.0003) and the recipient hepatitis C virus (HCV)
      status (HR = 1.53, 95% confidence interval = 1.04-2.24, P = 0.032) increased the
      risk of all-cause LGF in a Cox proportional hazards model adjusted for recipient
      race. Donor polymorphisms in TLR4 could be important factors in modulating TLR4
      activity and, therefore, affect the risk of graft loss. Additionally, there is a
      suggestion of an interaction between polymorphisms within TLR4 and the HCV
      status.

PMID- 22987290
TI  - Initial preclinical safety of non-replicating human endogenous retrovirus
      envelope protein-coated baculovirus vector-based vaccines against human
      papillomavirus.
AB  - Human endogenous retrovirus (HERV) envelope protein-coated, baculovirus vector
      based HPV 16 L1 (AcHERV-HPV16L1) is a non-replicating recombinant baculoviral
      vaccine. Here, we report an initial evaluation of the preclinical safety of
      AcHERV-HPV16L1 vaccine. In an acute toxicity study, a single administration of
      AcHERV-HPV16L1 DNA vaccine given intramuscularly (i.m.) to mice at a dose of 1 *
      10(8) plaque-forming units (PFU) did not cause significant changes in body weight
      compared with vehicle-treated controls. It did cause a brief increase in the
      weights of some organs on day 15 post-treatment, but by day 30, all organ weights
      were not significantly different from those in the vehicle-treated control group.
      No hematological changes were observed on day 30 post-treatment. In a range
      finding toxicity study with three doses of 1 * 10(7) , 2 * 10(7) and 5 * 10(7)
      PFU once daily for 5 days, the group treated with 5 * 10(7) PFU showed a
      transient decrease in the body weights from day 5 to day 15 post-treatment, but
      recovery to the levels similar to those in the vehicle-treated control group by
      post-treatment day 20. Organ weights were slightly higher for lymph nodes,
      spleen, thymus and liver after repeated dosing with 5 * 10(7) PFU on day 15, but
      had normalized by day 30. Moreover, repeated administration of AcHERV-HPV16L1 did
      not induce myosin-specific autoantibody in serum, and did not cause immune
      complex deposition or tissue damage at injection sites. Taken together, these
      results provide preliminary evidence of the preclinical safety of AcHERV-based
      HPV16L1 DNA vaccines in mice.

PMID- 22987291
TI  - Factors associated with rifampin resistance in staphylococcal periprosthetic
      joint infections (PJI): a matched case-control study.
AB  - PURPOSE: Rifampin combination therapy plays an important role in the management
      of staphylococcal periprosthetic joint infection (PJI). However, the emergence of
      rifampin resistance is a feared complication. We retrospectively analysed
      predetermined potential risk factors in patients with rifampin-resistant
      staphylococcal PJI in a multicentre case-control study. METHODS: Cases (n = 48)
      were defined as PJI caused by rifampin-resistant staphylococci. Rifampin
      susceptible controls (n = 48) were matched for microorganism and type of
      prosthetic joint. Uni- and multivariable conditional logistic regression analyses
      were performed to estimate odds ratios (OR) with 95 % confidence intervals (95 %
      CI). RESULTS: Forty-eight cases (31 men; median age 67 years; age range 39-88
      years) with hip- (n = 29), knee- (n = 13), elbow- (n = 4), shoulder- (n = 1) or
      ankle-PJI (n = 1) were enrolled in the study. Staphylococcus aureus and coagulase
      negative staphylococci were isolated in ten and 38 episodes, respectively. Most
      of the cases (n = 44, 92 %) had a previous PJI, and 93 % (n = 41) of these had
      been treated with rifampin. There was an independent association of emergence of
      rifampin resistance with male sex (OR 3.6, 95 % CI 1.2-11), >= 3 previous
      surgical revisions (OR 4.7, 95 % CI 1.6-14.2), PJI treatment with high initial
      bacterial load (inadequate surgical debridement, <2 weeks of intravenous
      treatment of the combination medication; OR 4.9, 95 % CI 1.6-15) and inadequate
      rifampin therapy (OR 5.4, 95 % CI 1.2-25). CONCLUSIONS: Based on our results,
      extensive surgical debridement and adequate antibiotic therapy are needed to
      prevent the emergence of rifampin resistance.

PMID- 22987292
TI  - Is genetic structure of the southern pygmy mouse Baiomys musculus (Cricetidae)
      related to human-induced spatial landscape heterogeneity in a tropical dry
      forest?
AB  - Tropical dry forests are biologically important biomes sustaining a high rate of
      endemic species. However, these forests are highly threatened by human activities
      that negatively impact them on distinct levels, including the genetic diversity.
      Within the framework of landscape genetics (that seeks to evaluate the relation
      of characteristics of the environmental matrix with population genetics), we used
      ISSR markers to evaluate the relationship between the alteration of tropical dry
      forest by human-induced activities (conserved vs. disturbed) with the genetic
      structure of four breeding sites of the southern pygmy mouse Baiomys musculus.
      Averaging among the 105 loci used, the unbiased heterozygosis per population
      (0.247-0.305) was statistically similar among the four sites, as well as between
      conserved and disturbed conditions (2-way ANOVA F ((3,16)) = 1.47, P = 0.1984).
      The genetic differentiation among the four breeding sites was high (F (ST) =
      0.1122; 95 % CI 0.082-0.146) considering the geographical scale evaluated (ca. 4
      km). Both, a factorial correspondence analysis and a model-based clustering
      analysis showed the existence of four genetic groups (one per breeding site).
      However, no association of genetic structure with disturbance conditions was
      revealed by these analyses. The absence of differences in mean genetic diversity
      and the lack of association of genetic structure with habitat transformation
      suggest that B. musculus has enough behavioral plasticity and enough genetic
      diversity to respond to environmental heterogeneity caused by human activities.
      We discussed conditions in which habitat transformation could indeed favor B.
      musculus.

PMID- 22987293
TI  - Recent duplications drive rapid diversification of trypsin genes in 12
      Drosophila.
AB  - Trypsin participates in many fundamental biological processes, the most notably
      in digesting food. The 12 species of Drosophila provide a great opportunity to
      analyze the duplication pattern of trypsins and their association with dietary
      changes. Here, we find that the trypsin family expands dramatically after
      speciation. The duplication events are strongly related to the host preferences,
      with significantly more copy numbers in species breeding on rotting fruits.
      Temporal analysis of the duplication events indicates that the occurrences of
      these events are not simultaneous, but rather correlate to the ecological change
      or host shift. Furthermore, we find that the specialists and generalists have
      different adaptive selections, which is revealed by dynamic duplication and/or
      deletion and relatively high Ka/Ks values on the duplicated events in
      specialists. Our findings suggest that the duplication of trypsin genes has
      played an important role in the adaption of Drosophila to the diverse ecosystems.

PMID- 22987295
TI  - Specific absorption rate reduction using nonlinear gradient fields.
AB  - The specific absorption rate is used as one of the main safety parameters in
      magnetic resonance imaging. The performance of imaging sequences is frequently
      hampered by the limitations imposed on the specific absorption rate that increase
      in severity at higher field strengths. The most well-known approach to reducing
      the specific absorption rate is presumably the variable rate selective excitation
      technique, which modifies the gradient waveforms in time. In this article, an
      alternative approach is introduced that uses gradient fields with nonlinear
      variations in space to reduce the specific absorption rate. The effect of such
      gradient fields on the relationship between the desired excitation profile and
      the corresponding radiofrequency pulse is shown. The feasibility of the method is
      demonstrated using three examples of radiofrequency pulse design. Finally, the
      proposed method is compared with and combined with the variable rate selective
      excitation technique.

PMID- 22987294
TI  - Role of CD61+ cells in thrombocytopenia of dengue patients.
AB  - Although hematological disorders with salient features of thrombocytopenia have
      been well documented in dengue patients, the role of CD61-expressing platelets
      and the megakaryocytic cell lineage in the pathogenesis of dengue virus (DENV)
      infection remains largely unexplored. A prospective observational study was
      performed using blood samples and PBMCs from dengue-confirmed patients, as well
      as from rhesus monkeys (RM) experimentally infected with DENV.
      Immunohistochemical staining and FACS techniques were applied to evaluate the
      frequencies of CD61(+) cells that contained DENV antigen. Highly enriched
      population of CD61(+) cells was also isolated from acute DENV-infected RM and
      assayed for DENV RNA by quantitative RT-PCR. Results revealed that DENV antigen
      was found in small vesicles of varying size, and more frequently in anucleated
      cells associated with platelets in dengue patients. The DENV antigen-containing
      cells were CD61(+) and appeared to share characteristics of megakaryocytes.
      Kinetic profiles of CD61(+) cells from DENV-infected RM revealed a transient
      increase in CD61(+)CD62P(+) cells early after DENV infection. DENV RNA in a
      highly enriched population of CD61(+) cells from the infected RM was observed
      during acute stage. Our results indicate that virus containing CD61(+) cells may
      be directly linked to the platelet dysfunction and low platelet count
      characteristics of dengue patients.

PMID- 22987296
TI  - Spatial characteristics of white matter abnormalities in schizophrenia.
AB  - There is considerable evidence implicating brain white matter (WM) abnormalities
      in the pathophysiology of schizophrenia; however, the spatial localization of WM
      abnormalities reported in the existing studies is heterogeneous. Thus, the goal
      of this study was to quantify the spatial characteristics of WM abnormalities in
      schizophrenia. One hundred and fourteen patients with schizophrenia and 138
      matched controls participated in this multisite study involving the Universities
      of Iowa, Minnesota, and New Mexico, and the Massachusetts General Hospital. We
      measured fractional anisotropy (FA) in brain WM regions extracted using 3
      different image-processing algorithms: regions of interest, tract-based spatial
      statistics, and the pothole approach. We found that FA was significantly lower in
      patients using each of the 3 image-processing algorithms. The region-of-interest
      approach showed multiple regions with lower FA in patients with schizophrenia,
      with overlap at all 4 sites in the corpus callosum and posterior thalamic
      radiation. The tract-based spatial statistic approach showed (1) global
      differences in 3 of the 4 cohorts and (2) lower frontal FA at the Iowa site.
      Finally, the pothole approach showed a significantly greater number of WM
      potholes in patients compared to controls at each of the 4 sites. In conclusion,
      the spatial characteristics of WM abnormalities in schizophrenia reflect a
      combination of a global low-level decrease in FA, suggesting a diffuse process,
      coupled with widely dispersed focal reductions in FA that vary spatially among
      individuals (ie, potholes). 

PMID- 22987297
TI  - Attentional modulation of source attribution in first-episode psychosis: a
      functional magnetic resonance imaging study.
AB  - BACKGROUND: In patients with schizophrenia, the misattribution of self-generated
      events to an external source is associated with the presence of psychotic
      symptoms. The aim of this study was to investigate how this misattribution is
      influenced by dysfunction of attentional processing, which is also impaired in
      schizophrenia. METHODS: Participants underwent functional Magnetic Resonance
      Imaging (fMRI) while listening to prerecorded speech. Their expectancies were
      manipulated using visual cues that were either congruent (valid) or incongruent
      (invalid) with the speech. The source (self/other) and the acoustic quality
      (undistorted/distorted) of the speech were also manipulated. Twenty patients with
      first-episode psychosis (FEP) and 20 matched healthy controls (HC) were tested.
      RESULTS: When listening to self-generated speech preceded by an invalid (other
      speech) cue, relative to HC, FEP patients showed a trend to misidentify their own
      speech as that of another person. Analysis of fMRI data showed that FEP patients
      had reduced activation in the right middle temporal gyrus (MTG) and left
      precuneus (Pc) relative to HC. Within the FEP group, the level of activation in
      the right MTG was negatively correlated with the severity of their positive
      psychotic symptoms. CONCLUSIONS: Impaired attentional modulation in schizophrenia
      may contribute to the tendency for FEP patients to misattribute the source of
      self-generated material, and this may be mediated by the right MTG and Pc,
      regions that are involved in both self-referential processing and the integration
      of sensory information.

PMID- 22987298
TI  - Mechanisms mediating the synergistic anticancer effects of combined gamma
      tocotrienol and sesamin treatment.
AB  - Epidemiological studies have highlighted the ability of phytochemicals to reduce
      the risk of breast cancer by attenuating specific intracellular signaling
      pathways that regulate cell proliferation and survival. gamma-Tocotrienol is a
      natural form of vitamin E that displays potent anticancer activity at doses that
      have no discernible toxicity toward normal cells. Sesamin is an abundant
      phytochemical found in sesame seed oil that also shows antiproliferative and
      antiangiogenic activity against human breast cancer cells. In this study, the
      combined treatment of subeffective doses of gamma-tocotrienol and sesamin caused
      a synergistic inhibition of murine +SA mammary epithelial cell growth, as
      determined by the MTT assay and immunofluorescent Ki-67 staining. Western blot
      studies revealed that combined low-dose treatment of gamma-tocotrienol and
      sesamin caused a marked reduction in EGF-induced ErbB3 and ErbB4 receptors
      phosphorylation (activation) and a relatively large decrease in intracellular
      levels of total and/or phosphorylated c-Raf, MEK1/2, ERK1/2, PI3K, PDK1, Akt, p
      NFkappaB, Jak1, Jak2, and Stat1, as compared to cells treated with only one
      compound or in the vehicle-treated control group. These findings demonstrate that
      the synergistic growth inhibitory effects of gamma-tocotrienol and sesamin
      treatment are associated with suppression of EGF-dependent mitogenic signaling in
      mammary tumor cells and suggest that dietary supplementation with these
      phytochemicals may provide some benefits in the prevention and/or treatment of
      breast cancer.

PMID- 22987302
TI  - An international comparison of male and female breast cancer incidence rates.
AB  - Global international trends in female breast cancer incidence have been described
      previously but no comparable analysis of male breast cancer incidence rates has
      been conducted. We obtained male and female case and population data using Cancer
      Incidence in Five Continents (CI5). We calculated age-adjusted, sex-specific
      incidence rates and female-to-male incidence rate ratios (FMIRRs) and compared
      trends of such for the period 1988-2002. This analysis included 8,681 male breast
      cancer cases and 1.14 million female breast cancer cases. The highest male
      incidence rate was observed in Israel at 1.24 per 100,000 man-years, and the
      highest female incidence rate was observed in the United States at 90.7 per
      100,000 woman-years. The lowest incidence rates for males (0.16) and females
      (18.0) were observed in Thailand. In general, male breast cancer incidence trends
      were variable; a minority of countries displayed evidence for an increase. In
      contrast, female incidence rates have been increasing in a majority of countries.
      The Pearson correlation coefficient (r) for male and female breast cancer
      incidence rates by country during 1988-2002 was 0.69. Male breast cancer rates
      were generally less than 1 per 100,000 man-years, in contrast to the much higher
      rates of female breast cancer, providing for an overall FMIRR of 122. The
      differences in both incidence rates and time trends between males and females may
      reflect sex differences in underlying risk factors, pathogenesis, and/or
      overdiagnosis. Conversely, the high correlation between male and female breast
      cancer incidences may indicate that both sexes share some common risk factors for
      breast cancer.

PMID- 22987303
TI  - Randomized clinical trial on the effect of coffee on postoperative ileus
      following elective colectomy.
AB  - BACKGROUND: Postoperative ileus is a common problem after abdominal surgery. It
      was postulated that coffee intake would decrease postoperative ileus after
      colectomy. METHODS: This was a multicentre parallel open-label randomized trial.
      Patients with malignant or benign disease undergoing elective open or
      laparoscopic colectomy were assigned randomly before surgery to receive either
      coffee or water after the procedure (100 ml three times daily). The primary
      endpoint was time to first bowel movement; secondary endpoints were time to first
      flatus, time to tolerance of solid food, length of hospital stay and
      perioperative morbidity. RESULTS: A total of 80 patients were randomized, 40 to
      each group. One patient in the water arm was excluded owing to a change in
      surgical procedure. Patient characteristics were similar in both groups. In
      intention-to-treat analysis, the time to the first bowel movement was
      significantly shorter in the coffee arm than in the water arm (mean(s.d.)
      60.4(21.3) versus 74.0(21.6) h; P = 0.006). The time to tolerance of solid food
      (49.2(21.3) versus 55.8(30.0) h; P = 0.276) and time to first flatus (40.6(16.1)
      versus 46.4(20.1) h; P = 0.214) showed a similar trend, but the differences were
      not significant. Length of hospital stay (10.8(4.4) versus 11.3(4.5) days; P =
      0.497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0.550) were
      comparable in the two groups. CONCLUSION: Coffee consumption after colectomy was
      safe and was associated with a reduced time to first bowel action.

PMID- 22987304
TI  - 'Living and dying well with end-stage liver disease': time for palliative care?

PMID- 22987305
TI  - Evidence of exposure to aristolochic acid in patients with urothelial cancer from
      a Balkan endemic nephropathy region of Romania.
AB  - Recently, chronic Aristolochia poisoning was found responsible for the aetiology
      of Balkan endemic nephropathy (BEN) in Croatia, Serbia, and Bosnia, and diet was
      the likely route of exposure to aristolochic acid (AA). BEN, often associated
      with an increased incidence of upper urinary tract carcinoma (UUC), also affects
      residents of certain rural villages in Romania. AA is a nephrotoxin and human
      carcinogen that forms DNA adducts after metabolic activation, which induce
      characteristic TP53 mutations in urothelial tumours. Here we present the first
      evidence linking AA exposure to UUC in residents of an endemic region in the
      Romanian Mehedinti County. DNA was extracted from kidney and tumour tissue of
      seven patients who underwent nephroureterectomy for UUC and resided in BEN
      villages (endemic group). Five patients with UUC from nonendemic villages served
      as controls. AA-DNA adducts (7-(deoxyadenosin-N(6) -yl)-aristolactam I),
      established biomarkers of AA exposure, were identified by (32)P-postlabelling in
      renal DNA of six patients from the endemic group and in one of the nonendemic
      group (adduct levels ranged from 0.3 to 6.5 adducts per 10(8) nucleotides).
      Additionally, an A to T transversion in TP53, a base substitution characteristic
      of AA mutagenic activity was found in urothelial tumour DNA of one patient from
      the endemic group. Our results provide a molecular link to the cause of
      urothelial tumours in BEN regions of Romania indicating that AA is the common
      aetiological agent for BEN across its numerous geographical foci.

PMID- 22987306
TI  - Parallel imaging and template-free patterning of self-assembled monolayers with
      soft linear microelectrode arrays.

PMID- 22987308
TI  - Incidental finding of alpha-methylacyl-CoA racemase deficiency in a patient with
      oculocutaneous albinism type 4.
AB  - Genome-wide studies may lead to the discovery of genetic variants of potential
      clinical importance beyond the aims of the study. We performed single nucleotide
      polymorphism array analysis in a boy with oculocutaneous albinism to identify
      copy-neutral regions of homozygosity harboring genes involved in melanin
      biosynthesis. An unanticipated homozygous deletion of chromosome 5p13.3 was
      discovered, encompassing not only the OCA gene SLC45A2, but also four additional
      genes. This led to an unexpected presymptomatic diagnosis of alpha-methylacyl-CoA
      racemase deficiency in the same patient.

PMID- 22987307
TI  - CXCL12 enhances human neural progenitor cell survival through a CXCR7- and CXCR4
      mediated endocytotic signaling pathway.
AB  - Chemokine CXCL12 is widely expressed in the central nervous system and essential
      for the proper functioning of human neural progenitor cells (hNPCs). Although
      CXCL12 is known to function through its receptor CXCR4, recent data have
      suggested that CXCL12 binds to chemokine receptor CXCR7 with higher affinity than
      to CXCR4. However, little is known about the function of CXCR7 in hNPCs. Using a
      primary hNPC culture system, we demonstrated that CXCL12 promotes hNPC survival
      in the events of camptothecin-induced apoptosis or growth factor deprivation, and
      that this effect requires both CXCR7 and CXCR4. Through fluorescence-activated
      cell sorting analysis and immunocytochemistry, we determined that CXCR7 is mainly
      localized in the early endosome, while CXCR4 is more broadly expressed at the
      cell surface and on both early and recycling endosomes. Furthermore, we found
      that endocytosis is required for the prosurvival function of CXCL12. Using dual
      color total internal reflection fluorescence microscopy and immunoprecipitation,
      we demonstrated that CXCR7 quickly trafficks to plasma membrane in mediating
      CXCL12 endocytosis and colocalizes with CXCR4 after CXCL12 treatment.
      Investigating the molecular mechanisms, we found that ERK1/2 endocytotic
      signaling pathway is essential for hNPC survival upon apoptotic challenges.
      Consistent with these findings, a significantly higher number of apoptotic NPCs
      were found in the developing brain of CXCR7 knockout mice. In conclusion, CXCL12
      protects hNPCs from apoptotic challenges through CXCR7- and CXCR4-mediated
      endocytotic signaling. Since survival of hNPCs is important for neurogenesis,
      CXCR7 may become a new therapeutic target to properly regulate critical processes
      of brain development.

PMID- 22987309
TI  - Cardiac myocyte-fibroblast interactions and the coronary vasculature.
AB  - Treatment of cardiovascular diseases relies on the ability not only to abrogate
      and compensate for congenital deformities but also to repair cardiac pathologies
      in the adult. Determining how cells communicate within the myocardium and how to
      use this communication to repair and treat pathological conditions have been
      necessary steps in the successful intervention of cardiac diseases. In this
      regard, research has mostly focused on relationships between the main cellular
      constituents of the heart, myocytes, and fibroblasts. However, the coronary
      vasculature is also critical to myocardial organization and integrity, and how
      the vasculature influences and responds to cues from cardiac myocytes and
      fibroblasts is largely underappreciated. This review discusses how factors that
      affect myocyte and fibroblast physiology and communication may also interact with
      the coronary vasculature. Defining the mechanisms of these cellular relationships
      will help identify ways to control angiogenesis during cardiac remodeling and the
      development of tissue-engineered therapies.

PMID- 22987311
TI  - The peroxisome proliferator-activated receptor-gamma agonist pioglitazone
      protects against cisplatin-induced renal damage in mice.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists not only
      improve metabolic abnormalities of diabetes and consequent diabetic nephropathy,
      but they also protect against non-diabetic kidney disease in experimental models.
      Here, we investigated the effect of PPAR-gamma agonist pioglitazone against acute
      renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single
      intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was
      administered for six consecutive days in doses of 15 or 30 mg kg(-1)  day(-1),
      per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to
      mice induced a marked renal failure, characterized by a significant increase in
      serum urea and creatinine levels and alterations in renal tissue architecture.
      Cisplatin exposure induced oxidative stress as indicated by decreased levels of
      non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels]
      and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD),
      catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and
      glutathione S-transferase(GST) activities)] in renal tissue. Administration of
      pioglitazone markedly protected against the increase in urea and creatinine
      levels and histological alterations in kidney induced by cisplatin treatment.
      Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by
      cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT,
      SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice.
      These results indicated that pioglitazone has a protective effect against
      cisplatin-induced renal damage in mice. The protection is mediated by preventing
      the decline of antioxidant status. The results have implications in use of PPAR
      gamma agonists in human application for protecting against drugs-induced
      nephrotoxicity.

PMID- 22987310
TI  - The origin and arrhythmogenic potential of fibroblasts in cardiac disease.
AB  - Fibroblasts play a major role in normal cardiac physiology and in the response of
      the heart to injury and disease. Cardiac electrophysiological research has
      primarily focused on the mechanisms of remodeling that accompany cardiac disease
      with an emphasis on myocyte electrophysiology. Recently, there has been
      increasing interest in the potential role of fibroblasts in cardiac
      electrophysiology. This review focuses on the arrhythmia mechanisms involving
      interactions between myocytes and fibroblasts. We also discuss the available
      evidence supporting the contribution of intracardiac and extracardiac sources to
      the fibroblast and myofibroblast populations in diseased hearts.

PMID- 22987312
TI  - Long-term safety and efficacy of imatinib mesylate (Gleevec(r)) in elderly
      patients with chronic phase chronic myelogenous leukemia: results of the AFR04
      study.
AB  - Data from registries suggest that the median age of chronic myelogenous leukemia
      (CML) patients is 10-15 years older than that of clinical trials. We conducted a
      prospective phase II study to evaluate imatinib mesylate (IM, 400 mg daily) in
      newly diagnosed chronic phase CML (CP-CML) patients. Patients aged 70 years and
      over diagnosed with CP-CML within 12 months were eligible. Thirty patients were
      enrolled from April 2002 to October 2004. Median age was 74.8 years (range, 70
      90). Male/female ratio was 1.72. At inclusion, comorbidities were reported in all
      but one patient, Cumulative Illness Rating Scale for Geriatrics comorbidity mean
      index was 1.47, and 66% of patients had cardiovascular disease. The median daily
      IM dose was 392 mg (range, 256-445). IM was interrupted in patients with severe
      comorbidities. Treatment discontinuation was observed in 36.6% of patients.
      Cumulative incidence of complete cytogenetic response was 71.4 and 78.5% at 12
      and 24 months, respectively. A high level of sustained responses was observed in
      patients with mild or moderate comorbidities. Seven-year estimated overall
      survival was 80.8% (95% CI: 59.0-91.7). Two-thirds of the patients were still on
      long-term therapy at cut-off, and no patients had died from progression. This
      trial was registered at http://www.clinicaltrials.gov as # NCT00219765.

PMID- 22987313
TI  - Excipient effects on humanized monoclonal antibody interactions with silicone oil
      emulsions.
AB  - The interfacial adsorption of three humanized monoclonal antibodies to emulsions
      of microdroplets of silicone oil was examined using indirect measurement via
      integrated peak areas in size-exclusion high-performance liquid chromatograms.
      The level of silicone oil far exceeded the typical levels used in prefillable
      syringes. The three antibodies rapidly adsorbed to silicone oil-water interfaces
      in various buffer formulations. Addition of 140 mM NaCl to solutions buffered
      with 10 mM l-histidine, pH 6.0, increased the amount of protein adsorbed.
      Conversely, the extent of adsorption was significantly decreased by the addition
      of 0.03% (w/v) Tween(r) 20. Stern-Volmer constants determined from intrinsic
      tryptophan fluorescence quenching by acrylamide suggested that the tertiary
      structure of the adsorbed antibodies was significantly perturbed. However, no
      aggregation or precipitation of the antibodies was detected. Flow cytometric
      analysis of emulsions of fluorescently stained silicone oil in solutions
      containing fluorescently labeled antibodies and light microscopy experiments
      suggested that agglomeration of silicone oil droplets in the emulsions occurred.
      Zeta potentials measured for silicone oil microdroplets with adsorbed antibodies
      suggested that droplet agglomeration was probably the result of reduced
      electrostatic energy barriers to droplet collisions.

PMID- 22987314
TI  - Preserving the morphology and evaluating the quality of liver grafts by
      hypothermic machine perfusion: a proof-of-concept study using discarded human
      livers.
AB  - The wider use of livers from expanded criteria donors and donation after
      circulatory death donors may help to improve access to liver transplantation. A
      prerequisite for safely using these higher risk livers is the development of
      objective criteria for assessing their condition before transplantation. Compared
      to simple cold storage, hypothermic machine perfusion (HMP) provides a unique
      window for evaluating liver grafts between procurement and transplantation. In
      this proof-of-concept study, we tested basic parameters during HMP that may
      reflect the condition of human liver grafts, and we assessed their morphology
      after prolonged HMP. Seventeen discarded human livers were machine-perfused.
      Eleven livers were nontransplantable (major absolute contraindications and severe
      macrovesicular steatosis in the majority of the cases). Six livers were found in
      retrospect to be transplantable but could not be allocated and served as
      controls. Metabolic parameters (pH, lactate, partial pressure of oxygen, and
      partial pressure of carbon dioxide), enzyme release in the perfusate [aspartate
      aminotransferase (AST) and lactate dehydrogenase (LDH)], and arterial/portal
      resistances were monitored during HMP. Nontransplantable livers released more AST
      and LDH than transplantable livers. In contrast, arterial/portal vascular
      resistances and metabolic profiles did not differ between the 2 groups.
      Morphologically, transplantable livers remained well preserved after 24 hours of
      HMP. In conclusion, HMP preserves the morphology of human livers for prolonged
      periods. A biochemical analysis of the perfusate provides information reflecting
      the extent of the injury endured.

PMID- 22987315
TI  - Influence of white matter fiber orientation on R2* revealed by MRI segmentation.
AB  - PURPOSE: To investigate white matter heterogeneity using a multichannel
      segmentation of a large sample of structural and diffusion magnetic resonance
      imaging (MRI) data. MATERIALS AND METHODS: A sample of 50 subjects was segmented
      using channels comprising exclusively structural (longitudinal and transverse
      relaxation times T1 and T2 and transverse relaxation rate R2*) and diffusion
      based MRI indices (mean diffusivity and fractional anisotropy). These data were
      analyzed using a data driven approach in which no prior information was used.
      RESULTS: The analysis revealed the splitting of white matter into two subclasses
      in which the longitudinal fasciculi were distinguished from inferior/superior
      ones. The distribution of the adopted indices in the obtained clusters showed
      that R2* was mainly responsible for this splitting. CONCLUSION: This result
      supports the observation, previously hypothesized in the literature, that R2* is
      influenced by the fiber orientation.

PMID- 22987316
TI  - The genotypes of citrus tristeza virus isolates from China revealed by sequence
      analysis of multiple molecular markers.
AB  - The genotypes of ten citrus tristeza virus (CTV) isolates from central China were
      determined by examining multiple molecular markers (MMMs) using 11 primer pairs.
      The results revealed that one isolate contained a single T30 genotype, two
      isolates contained a single VT genotype, and the other seven isolates were
      mixtures of two or more genotypes. Sequence analysis of amplified MMMs showed a
      high genetic diversity in Chinese CTV populations. The genotypes resembling T36,
      RB and B165 were identified from Chinese CTV isolates for the first time. Our
      results suggest that genotype assignment of CTV cannot be based solely on the
      amplification profiles of MMMs, and sequencing of MMMs is required.

PMID- 22987317
TI  - Reactive polymer as a versatile toolbox for construction of multifunctional
      superparamagnetic nanocomposites.
AB  - The development of magnetic nanoparticles with multiple functions has been an
      ever-growing field because of their diverse applications in drug delivery,
      biosensing, cell labeling, and so on. In this study, a facile method was
      developed to construct multifunctional magnetic nanocomposites. The approach is
      based on the use of poly(glycidyl methacrylate), PGMA, with numerous epoxy groups
      as reactive polymer to combine with fluorescent dye, the surface of magnetic
      nanoparticles, and targeting ligands directly without expatiatory functionality
      design. The resultant nanocomposites with good superparamagnetic and fluorescent
      properties could be exploited for bioimaging. Moreover, after conjugation with a
      model protein, namely, transferrin, which specifically targets cells
      overexpressing transferrin receptors, the nanocomposites could be used
      selectively to recognize Hela cells in comparison with nonconjugated ones. These
      results indicate that the newly designed magnetic nanocomposites with PGMA as
      functional polymer could serve as a novel versatile platform to conjugate with
      various molecules for construction of diverse multifunctional magnetic
      nanocomposites to meet different requirements and potential uses in nanomedicine
      and biological chemistry.

PMID- 22987319
TI  - Induction of cytokines, MMP9, TIMPs, RANKL and OPG during orthodontic tooth
      movement.
AB  - This controlled longitudinal intervention study investigated changes in cytokines
      and biomarkers of bone and tissue metabolism within gingival crevicular fluid
      (GCF) from patients undergoing orthodontic treatment. GCF was collected on
      PeriopaperTM strips (Oraflow Inc., USA) from 20 volunteers at baseline, before
      tooth extraction and appliance placement and then at intervals during orthodontic
      treatment. Samples were taken 10 weeks following first appliance placement: at
      four hours; 7 days; and 42 days after application of distalising forces to
      maxillary canine teeth. Cytokines (GM-CSF, interferon-gamma, IL-1beta, IL-2, IL
      4, IL-5, IL-6, IL-8, IL-10 and TNFalpha), tissue biomarkers (MMP-9, TIMP-1 & 2)
      and bone metabolism indicators (RANKL and OPG) were measured in GCF using
      multiplex assays. Tension sites adjacent to canines showed significant increases
      in IL-1beta, IL-8, TNFalpha, MMP-9 and TIMPs 1 and 2 across all time points
      following force application, while compression sites exhibited increases in IL
      1beta and IL-8 after 4 hours, MMP-9 after 7 and 42 days and RANKL after 42 days.
      These data demonstrate that high levels of pro-inflammatory cytokines and
      biomarkers of tissue and bone metabolism in GCF are associated with orthodontic
      force application. Elevated levels were evident at 4 hours but continued for
      periods of up to 6 weeks. The data suggest that GCF biomarker analysis may help
      optimise orthodontic forces for individual patients. 

PMID- 22987321
TI  - Measuring glucose concentrations in the rat brain using echo-time-averaged point
      resolved spectroscopy at 7 tesla.
AB  - Glucose has multiple functions in the brain, and there is interest in estimating
      in vivo concentrations rather than merely the uptake determined by nuclear
      medicine. Glucose can be estimated using magnetic resonance spectroscopy, but
      measurement is difficult due to its multiple J-coupled proton signals overlapping
      with other metabolite signals. To minimize the effect of interfering signals,
      echo time (TE) values between 60 and 95 ms were averaged, and the loss in signal
      due to the T2 effect was corrected in both the estimation of glucose
      concentration and in creation of the basis files for fitting. The effectiveness
      of the TE-averaging method was evaluated by measuring the glucose concentration
      in fasted rats before and after feeding. The brain glucose in all rats increased
      after feeding with fasted and fed glucose-to-creatine ratios of 0.15 +/- 0.03 and
      0.24 +/- 0.04, respectively. Data at a short TE of 13 ms measured ratios of 0.30
      +/- 0.16 and 0.36 +/- 0.24 for the fasted and fed rats, respectively,
      demonstrating the difficulty in obtaining reliable glucose measurements at short
      TE. Overall, TE averaging minimizes the influence of macromolecular signals and
      nearby peaks to give precise, consistent estimates of glucose.

PMID- 22987323
TI  - Platelet-rich plasma-loaded chitosan scaffolds: preparation and growth factor
      release kinetics.
AB  - The aim of this study is to compare the effects of different platelet-rich plasma
      (PRP) preparation methods on platelet activity and to investigate the growth
      factor (GF) release kinetics from PRP-loaded chitosan scaffolds for tissue
      engineering applications. Flow cytometry analysis showed that centrifugation
      processes used for PRP preparation did not cause significant effect on platelet
      activation levels by means of markers investigated. Two different methods were
      used to prepare PRP-loaded chitosan scaffolds: (i) PRP was added to chitosan gel
      before freeze-drying to prepare scaffolds called as "GEL" and (ii) PRP was
      embedded to freeze-dried chitosan scaffolds to prepare scaffolds called as
      "SPONGE." In addition, nonactivated PRP and PRP activated with type-I collagen
      were used as control groups. Scanning electron microscopy images demonstrated
      that, in GEL group, there is no deterioration on the scaffolds porous, 3D, and
      interconnected structure. GF release kinetics was determined by enzyme-linked
      immunosorbent assay for platelet-derived GF-BB, transforming GF-beta1, and
      insulin-like GF-1. A sustained release of GFs was achieved in GEL group while a
      sharp burst release was observed for all the GFs from the SPONGE groups.
      Moreover, platelet-derived GF-BB, insulin-like GF-1, and transforming GF-beta1
      releases were prolonged to 20 days in GEL groups, and the biological activities
      of all GFs released from GEL and SPONGE scaffolds were preserved. This study
      demonstrated that chitosan scaffold that was called GEL could be an appropriate
      carrier for PRP applications by providing sustained release of GFs.

PMID- 22987320
TI  - Anticoagulation in heart failure: current status and future direction.
AB  - Despite therapeutic advances, patients with worsening heart failure (HF)
      requiring hospitalization have unacceptably high post-discharge mortality and re
      admission rates soon after discharge. Evidence suggests a hypercoagulable state
      is present in patients with HF. Although thromboembolism as a direct consequence
      of HF is not frequently clinically recognized, it may contribute to mortality and
      morbidity. Additionally, many patients with HF have concomitant disorders
      conferring additional thrombotic risk, including atrial fibrillation (AF) and
      coronary artery disease (CAD). Acute coronary syndrome (ACS), a known consequence
      of coronary thrombosis, is a common precipitating factor for worsening HF.
      Coronary thrombosis may also cause sudden death in patients with HF and CAD.
      Because data are largely derived from observational studies or trials of modest
      size, guideline recommendations on anticoagulation for HF vary between
      organizations. The recently presented Warfarin versus Aspirin in Reduced Cardiac
      Ejection Fraction trial of HF patients in sinus rhythm suggested anticoagulation
      reduces the risk of stroke, although rates of the combined primary endpoint
      (death, ischemic stroke, or intracerebral hemorrhage) were similar for
      acetylsalicylic acid and warfarin. Newer oral anticoagulants dabigatran,
      apixaban, and rivaroxaban have successfully completed trials for the prevention
      of stroke in patients with AF and have shown benefits in the subpopulation of
      patients with concomitant HF. Positive results of the Anti-Xa Therapy to Lower
      Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute
      Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2-TIMI 51)
      trial of rivaroxaban in ACS are also encouraging. These data suggest there is a
      need to assess the potential role for these newer agents in the management of
      patients hospitalized for HF who continue to have a high post-discharge event
      rate despite available therapies. 

PMID- 22987324
TI  - Dating the origin and dispersal of hepatitis B virus infection in humans and
      primates.
AB  - The origin of hepatitis B virus (HBV) infection in humans and other primates
      remains largely unresolved. Understanding the origin of HBV is crucial because it
      provides a framework for studying the burden, and subsequently the evolution, of
      HBV pathogenicity with respect to changes in human population size and life
      expectancy. To investigate this controversy we examined the relationship between
      HBV phylogeny and genetic diversity of modern humans, investigated the timescale
      of global HBV dispersal, and tested the hypothesis of HBV-human co-divergence. We
      find that the global distribution of HBV genotypes and subgenotypes are
      consistent with the major prehistoric modern human migrations. We calibrate the
      HBV molecular clock using the divergence times of different indigenous human
      populations based on archaeological and genetic evidence and show that HBV jumped
      into humans around 33,600 years ago; 95% higher posterior density (HPD): 22,000
      47,100 years ago (estimated substitution rate: 2.2 * 10(-6) ; 95% HPD: 1.5-3.0 *
      10(-6) substitutions/site/year). This coincides with the origin of modern non
      African humans. Crucially, the most pronounced increase in the HBV pandemic
      correlates with the global population increase over the last 5,000 years. We also
      show that the non-human HBV clades in orangutans and gibbons resulted from cross
      species transmission events from humans that occurred no earlier than 6,100 years
      ago. CONCLUSION: Our study provides, for the first time, an estimated timescale
      for the HBV epidemic that closely coincides with dates of human dispersals,
      supporting the hypothesis that HBV has been co-expanding and co-migrating with
      human populations for the last 40,000 years. (HEPATOLOGY 2013).

PMID- 22987326
TI  - Gender-related differences in the obstructive sleep apnea syndrome.
AB  - The obstructive sleep apnea syndrome (OSAS) is associated with increased
      morbidity and mortality. Epidemiological studies suggest a two-fold higher
      prevalence of OSAS in men than in women. Differences in pharyngeal collapsibility
      and central respiratory drive may play a significant role in the gender-specific
      pathogenesis. Compared with their male counterparts, female patients experience
      OSAS at an older age (postmenopausal) and with higher body-mass-index. Female
      OSAS patients furthermore more frequently report atypical symptoms, such as
      insomnia, depression, and/or restless legs, and thus are less likely to be
      referred for the evaluation of sleep disordered breathing. Knowledge about these
      distinct gender-related differences in clinical features of OSAS may contribute
      to an increased awareness, improved diagnosis and its therapeutic consequences.

PMID- 22987325
TI  - Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic
      airway inflammation in mice.
AB  - We previously found that mesenchymal stem cells (MSCs) derived from human-induced
      pluripotent stem cells (iPSCs) exerted immunomodulatory effects on Th2-mediated
      allergic rhinitis in vitro. However, their contribution to the asthma and
      allergic rhinitis in animal models remains unclear. In this study, we developed a
      mouse model of ovalbumin (OVA)-induced allergic inflammation in both the upper
      and lower airways and evaluated the effects of the systemic administration of
      human iPSC-MSCs and bone marrow-derived MSCs (BM-MSCs) on allergic inflammation.
      Our results showed that treatments with both the iPSC-MSCs and BM-MSCs before the
      challenge phase protected the animals from the majority of allergy-specific
      pathological changes. This protection included an inhibition of inflammatory cell
      infiltration and mucus production in the lung, a reduction in eosinophil
      infiltration in the nose, and a decrease in inflammatory cell infiltration in
      both the bronchoalveolar and nasal lavage fluids. In addition, treatment with
      iPSC-MSCs or BM-MSCs before the challenge phase resulted in reduced serum levels
      of Th2 immunoglobulins (e.g., IgE) and decreased levels of Th2 cytokines
      including interleukin (IL)-4, IL-5, or IL-13 in the bronchoalveolar and/or nasal
      lavage fluids. Similar therapeutic effects were observed when the animals were
      pretreated with human iPSC-MSCs before the sensitization phase. These data
      suggest that iPSC-MSCs may be used as an alternative strategy to adult MSCs in
      the treatment of asthma and allergic rhinitis.

PMID- 22987327
TI  - [Technique and clinical importance of breathing wave generators].
AB  - In recent years, several comparisons of ventilators for invasive and noninvasive
      mechanical ventilation or automatic continuous pressure therapy (APAP) were
      published. Simulations were used with different test sequences. Simulations are
      particularly helpful when identical breathing patterns should be reproduced
      several times. In the following we report on recent developments of flow- and
      lung simulators from other groups and present our own experiences in Hagen. To
      study automatic CPAP devices we applied a custom-made simulator which reproduces
      the obstruction of the upper airway and any breathing waveform. From the
      different behavior of automatic CPAP devices concerning pressure dynamics
      important conclusions can be drawn about the real clinical situation.

PMID- 22987328
TI  - Plant growth promoting bacteria in Brachiaria brizantha.
AB  - Brachiaria brizantha is considered one of the preferred fodders among farmers for
      having high forage yield and large production of root mass. The association of
      beneficial bacteria with these grasses can be very valuable in the recovery of
      the pasture areas with nutritional deficiency. With the aim of studying this
      possibility, we carried out the sampling of soil and roots of B. brizantha in
      three areas (Nova Odessa-SP, Sao Carlos-SP and Campo Verde-MT, Brazil). Seventy
      two bacterial strains were isolated and used in tests to evaluate their
      biotechnological potential. Almost all isolates presented at least one positive
      feature. Sixty-eight isolates produced analogues of indole-3-acetic acid, ten
      showed nitrogenase activity when subjected to the method of increasing the
      concentration of total nitrogen (total N) in the culture medium and sixty-five
      isolates showed nitrogenase activity when subjected to acetylene reduction
      technique. The partial sequencing of 16S rRNA of these isolates allowed the
      identification of seven main groups, with the prevalence of those affiliated to
      the genus Stenotrophomonas (69 %). At the end, this work elected the strains C4
      (Pseudomonadaceae) and C7 (Rhodospirillaceae) as promising organisms for the
      development of inoculants due to their higher nitrogenase activity.

PMID- 22987329
TI  - Animal models for studying microglia: the first, the popular, and the new.
AB  - Microglia, the resident phagocytes of brain, have been intensively studied since
      their discovery in the 1920s. There is no doubt that the possibility of culturing
      microglia in vitro has advanced enormously our understanding of these cells.
      However, as we know today, that microglia react to even small changes in the
      brain, it is crucial to also study these cells by preserving as much as possible
      their natural environment. Nowadays, advances in imaging technologies and
      transgenic cell labeling methods allow the direct observation of cells at work.
      These in vivo approaches have already changed our view on microglia by showing
      that these cells are active even in the healthy adult brain. As today, there is
      upcoming evidence that microglia can directly influence neuronal activity,
      understanding their roles and, in particular, their interactions with neurons is
      of great importance. The aim of this review is to illustrate three animal models
      that are currently used for microglial research and to discuss their
      characteristics and advantages by presenting recent achievements in microglial
      research. In our view the availability of different systems for studying
      microglia will lead to a more comprehensive understanding of their functions.

PMID- 22987330
TI  - A method to predict the equilibrium solubility of drugs in solid polymers near
      room temperature using thermal analysis.
AB  - A method is presented for determining the equilibrium solubility of a drug in a
      solid polymer at or near room temperature, which represents a typical storage
      temperature. The method is based on a thermodynamic model to calculate the Gibbs
      energy change DeltaG(SS) associated with forming a binary drug-polymer solid
      solution from the unmixed polymer and solid drug. The model includes
      contributions from heat capacity differences between the solid solution and the
      corresponding unmixed components, breaking up of the solid drug structure, and
      drug-polymer mixing. Calculation of DeltaG(SS) from thermal analysis data is
      demonstrated, and it is shown that minima of plots of DeltaG(SS) versus the
      dissolved drug concentration represent the equilibrium drug solubility in the
      polymer. Solid solutions were produced for drug-polymer systems (griseofulvin,
      indomethacin, itraconazole; PVP K30, Eudragit L100, Eudragit E100) in drug weight
      fractions up to ~25%. At 25 degrees C, it was seen that heat capacity effects
      were important in determining the drug solubility. It was concluded that drug
      solubilities in solid polymers can be determined using thermal analysis, and must
      include heat capacity effects when evaluated near room temperature.

PMID- 22987331
TI  - Using age-referenced prostate-specific antigen percentile to predict survival
      outcomes in screened Taiwanese men.
AB  - The survival outcomes of Asian men with elevated prostate-specific antigen (PSA)
      levels at screening are largely unknown. We present the clinical outcomes of
      Taiwanese men based on their screening PSA levels. Between 1994 and 2006, 27,761
      men aged over 40 years underwent PSA screening in a self-funded health
      examination. The clinical database was linked with the national cancer and death
      registry databases to generate prostate cancer incidence, prostate cancer
      mortality (PCM) and overall mortality (OM). Participants were followed until the
      end of 2009. Survival analyses were performed for the participants' outcomes, and
      were stratified by five 10-year age strata (age 40-<50, 50-<60, 60-<70, 70-<80
      and >= 80), and six age-referenced PSA percentile groups, divided by the 50th,
      75th, 90th, 95th and 99 th percentile of PSA values for each 10-year age stratum.
      The median age of the 27,761 men was 54.7 years. The median PSA level at cancer
      diagnosis was 4.46 ng ml(-1) . Specifically, the PSA levels for the five 10-year
      age strata in order of respectively increasing ages were 1.93, 3.50, 4.10, 6.94
      and 12.4 ng ml(-1) . After a median follow-up of 8.4 years, 2,463 men died and
      337 were diagnosed with prostate cancer. Among the 337 patients, 29 (8.6%) died
      of prostate cancer. The prostate cancer incidence, PCM and OM rates were higher
      in men with higher age-referenced PSA percentile values. The 10-year PCM rate for
      men with >= the 99th age-referenced PSA percentile was 3.9%, which was
      significantly higher than the rate of <= 0.5% in the lower percentile groups.

PMID- 22987332
TI  - Cancer statistics for Hispanics/Latinos, 2012.
AB  - Hispanics/Latinos are the largest and fastest growing major demographic group in
      the United States, accounting for 16.3% (50.5 million/310 million) of the US
      population in 2010. In this article, the American Cancer Society updates a
      previous report on cancer statistics for Hispanics using incidence data from the
      National Cancer Institute, the Centers for Disease Control and Prevention, and
      the North American Association of Central Cancer Registries and mortality data
      from the National Center for Health Statistics. In 2012, an estimated 112,800 new
      cases of cancer will be diagnosed and 33,200 cancer deaths will occur among
      Hispanics. In 2009, the most recent year for which actual data are available,
      cancer surpassed heart disease as the leading cause of death among Hispanics.
      Among US Hispanics during the past 10 years of available data (2000-2009), cancer
      incidence rates declined by 1.7% per year among men and 0.3% per year among
      women, while cancer death rates declined by 2.3% per year in men and 1.4% per
      year in women. Hispanics have lower incidence and death rates than non-Hispanic
      whites for all cancers combined and for the 4 most common cancers (breast,
      prostate, lung and bronchus, and colorectum). However, Hispanics have higher
      incidence and mortality rates for cancers of the stomach, liver, uterine cervix,
      and gallbladder, reflecting greater exposure to cancer-causing infectious agents,
      lower rates of screening for cervical cancer, differences in lifestyle and
      dietary patterns, and possibly genetic factors. Strategies for reducing cancer
      risk among Hispanics include increasing utilization of screening and available
      vaccines, as well as implementing effective interventions to reduce obesity,
      alcohol consumption, and tobacco use.

PMID- 22987333
TI  - fMRI of human olfaction at the individual level: interindividual variability.
AB  - PURPOSE: To determine whether the range of normal variation of human olfactory
      functional magnetic resonance imaging (fMRI) activations in healthy single
      subjects is compatible with the detection of atypical patterns. MATERIALS AND
      METHODS: In an event-related olfactory experiment, the variability of fMRI
      activation in six bilateral olfactory areas known to be affected in
      neurodegenerative diseases was measured in a region of interest (ROI) analysis in
      terms of intensity, localization, and overlap on 51 subjects. fMRI measurements
      were compared against measurements from a visual experiment performed on 25
      subjects. RESULTS: Olfaction induced activations with low intensity, high
      variability, and a 4-fold lower contrast-to-noise ratio (CNR) than vision. Even
      in the best case (piriform cortex), mean pairwise activation overlap was still
      less than 40%. None of the olfactory ROIs showed significant activation for all
      subjects at the permissive threshold of P < 0.001. A gender-dependent
      significantly stronger activation was found in the bilateral piriform cortex of
      male subjects. CONCLUSION: Linking t-statistics and CNR showed that for all
      olfactory ROIs, CNR is either near or below the estimated threshold of 0.73 found
      to be necessary to obtain significant activations. In our experimental conditions
      the low reliability of olfactory activations should prompt major reservations
      over using fMRI of human olfaction as a diagnostic tool in single subjects.

PMID- 22987335
TI  - Use of routine ultrasound-guided fine-needle aspiration cytology to assess the
      neck in patients with head and neck squamous cell carcinoma.

PMID- 22987334
TI  - Pyrrole-imidazole polyamides distinguish between double-helical DNA and RNA.
AB  - Groove specificity: pyrrole-imidazole polyamides are well-known for their
      specific interactions with the minor groove of DNA. However, polyamides do not
      show similar binding to duplex RNA, and a structural rationale for the molecular
      level discrimination of nucleic acid duplexes by minor-groove-binding ligands is
      presented.

PMID- 22987336
TI  - Heterogeneous growth patterns in carriers of chromosome 7p12.2 imbalances
      affecting GRB10.
AB  - Chromosomal duplications and deletions in 7p12.2 have been described in patients
      with growth disturbance phenotypes, that is, Silver-Russell and Beckwith
      Wiedemann syndrome (SRS, BWS). The region harbors the imprinted GRB10/Grb10 gene
      which has been postulated to belong to a major fetal growth pathway. Based on its
      genomic localization, its physiological function and its imprinting status,
      GRB10/Grb10 was considered as a candidate for growth disturbance disorders.
      However, based on case reports with imbalances of the GRB10 locus it has been
      suggested that the altered GRB10 copy number should be responsible for the
      aberrant growth phenotype rather than an altered imprinting status of the gene.
      We now report on a patient with an increased height and weight in his first years
      of life carrying a de-novo duplication (5.1 Mb) of paternal 7p12.2 material. The
      increased growth in this patient again contradicts the hypothesis that a gain of
      GRB10 copies leads to growth restriction. Indeed, it is necessary to compare the
      regions of imbalances in 7p12 and the affected genes in the different patients as
      other genes than GRB10 in 7p12 might cause these aberrant growth phenotypes.

PMID- 22987337
TI  - Magnetic resonance spectroscopy of the normal cerebellum: what degree of
      variability can be expected?
AB  - The objectives of this paper are (a) to establish the reliability of relative
      metabolite concentrations determined with (1)H-MR spectroscopy of the cerebellum
      using a method appropriate to the constraints of clinical radiology and (b) to
      record normal values for metabolites within the cerebellum and to look for
      differences in metabolite concentrations between the cerebellar hemispheric white
      matter and the superior vermis. 3-T (1)H-MR spectra were obtained from voxels
      positioned in the right cerebellar hemispheric white matter and the superior
      vermis in 55 healthy adults (mean age 41 years, range 20 to 77) using a single
      voxel PRESS sequence (TR/TE = 2,000/144 ms). One volunteer (male, age 34 years)
      was examined in six separate sessions over a period of 3 weeks. Reliability of
      intra- and inter-subject metabolite fitted area ratios was determined by
      evaluating coefficients of variance (%). Inter- and intra-subject coefficients of
      variance (%) in metabolite ratios were consistently lower in the vermis (4 to
      11.6) compared to those of the hemisphere (7.2 to 14.3). Cho/Cr was significantly
      higher in the vermis (0.83 +/- 0.10) compared to the hemisphere (0.76 +/- 0.11)
      and NAA/Cho was significantly lower in the vermis (1.19 +/- 0.12) compared to the
      hemisphere (1.35 +/- 0.16). Low inter- and intra-subject variability can be
      achieved when using a (1)H-MR spectroscopy technique that is appropriate to the
      time constraints of clinical radiology. The regional variations of Cho/Cr and
      NAA/Cho within the hemisphere and vermis should be considered when performing
      studies of diseases, which may preferentially target a particular cerebellar
      location.

PMID- 22987339
TI  - Water-immersion restraint stress disrupts nonenzymatic antioxidant defense
      systems through rapid and continuous ascorbic acid depletion in the adrenal gland
      of rats.
AB  - We examined whether water-immersion restraint stress (WIRS) disrupts nonenzymatic
      antioxidant defense systems through ascorbic acid depletion in the adrenal gland
      of rats. Rats were exposed to WIRS for 0.5, 1.5, 3 or 6 h. WIRS increased serum
      adrenocorticotropic hormone, corticosterone and glucose concentrations and
      adrenal corticosterone content at each time point. WIRS increased adrenal lipid
      peroxide content at 3 and 6 h, and the increase was twofold higher than the
      unstressed level at 6 h. WIRS decreased adrenal ascorbic acid content at each
      time point, and the decrease reached one-third of the unstressed level at 6 h.
      WIRS increased adrenal reduced glutathione content at 0.5 and 6 h but reduced
      that content to half of the unstressed level at 6 h. WIRS increased adrenal alpha
      tocopherol content at 1.5 h but returned that content to the unstressed level
      thereafter. When rats with 6 h of WIRS was orally preadministered with l-ascorbic
      acid (250 mg/kg), WIRS-induced changes in adrenal lipid peroxide, ascorbic acid
      and reduced glutathione contents were attenuated without any change in stress
      response. These results indicate that WIRS disrupts nonenzymatic antioxidant
      defense systems through rapid and continuous ascorbic acid depletion in the
      adrenal gland of rats.

PMID- 22987338
TI  - Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant
      Staphylococcus aureus and improves wound healing in a mouse model of infected
      skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion.
AB  - Photodynamic therapy (PDT) is an alternative treatment for infections that can
      kill drug resistant bacteria without damaging host-tissue. In this study we used
      bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin
      abrasion model, to investigate the effect of PDT on bacterial inactivation and
      wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and
      toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria
      in vivo and the possible recurrence in the days post-treatment were monitored by
      real-time bioluminescence imaging, and wound healing by digital photography. The
      results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to
      inhibit bacterial re-growth after the treatment and to significantly accelerate
      the wound healing process ((c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). 

PMID- 22987340
TI  - Synthesis and characterization of rhenabenzyne complexes.
AB  - Reactions of [ReH(5)(PMe(2)Ph)(3)] with alkynols HC=CC(OH)(R)C=CSiMe(3) (R=tBu,
      iPr, 1-adamantyl) in the presence of HCl give the vinylcarbyne complexes
      [Re{=CCH=C(R)C=CSiMe(3)}Cl(2)(PMe(2)Ph)(3)], which react with tBuMgCl to give
      [Re{=CCH=C(R)C=CSiMe(3)}HCl(PMe(2)Ph)(3)]. Treatment of
      [Re{=CCH=C(R)C=CSiMe(3)}HCl(PMe(2)Ph)(3)] with nBu(4)NF gives
      [Re{=CCH=C(R)C=CH}HCl(PMe(2)Ph)(3)], which first isomerizes to the bicyclic
      complexes [Re{CH=CH-C(R)=CCH=}Cl(PMe(2)Ph)(3)], and then to the rhenabenzynes
      [Re{=CCH=C(R)CH=CH}Cl(PMe(2)Ph)(3)]. The NMR spectroscopic and structural data as
      well as the aromatic stabilization energy (ASE) and nucleus-independent chemical
      shift (NICS) values suggest that these rhenabenzynes have aromatic character.

PMID- 22987341
TI  - Architectural specialization of the intrinsic thoracic limb musculature of the
      American badger (Taxidea taxus).
AB  - Evaluation of the relationships between muscle structure and digging function in
      fossorial species is limited. Badgers and other fossorial specialists are
      expected to have massive forelimb muscles with long fascicles capable of
      substantial shortening for high power and applying high out-force to the
      substrate. To explore this hypothesis, we quantified muscle architecture in the
      thoracic limb of the American badger (Taxidea taxus) and estimated the force,
      power, and joint torque of its intrinsic musculature in relation to the use of
      scratch-digging behavior. Architectural properties measured were muscle mass,
      belly length, fascicle length, pennation angle, and physiological cross-sectional
      area. Badgers possess hypertrophied shoulder flexors/humeral retractors, elbow
      extensors, and digital flexors. The triceps brachii is particularly massive and
      has long fascicles with little pennation, muscle architecture consistent with
      substantial shortening capability, and high power. A unique feature of badgers is
      that, in addition to elbow joint extension, two biarticular heads (long and
      medial) of the triceps are capable of applying high torques to the shoulder joint
      to facilitate retraction of the forelimb throughout the power stroke. The massive
      and complex digital flexors show relatively greater pennation and shorter
      fascicle lengths than the triceps brachii, as well as compartmentalization of
      muscle heads to accentuate both force production and range of shortening during
      flexion of the carpus and digits. Muscles of most functional groups exhibit some
      degree of specialization for high force production and are important for
      stabilizing the shoulder, elbow, and carpal joints against high limb forces
      generated during powerful digging motions. Overall, our findings support the
      hypothesis and indicate that forelimb muscle architecture is consistent with
      specializations for scratch-digging. Quantified muscle properties in the American
      badger serve as a comparator to evaluate the range of diversity in muscle
      structure and contractile function that exists in mammals specialized for
      fossorial habits.

PMID- 22987343
TI  - Super-secondary structure: a historical perspective.
AB  - The history of the concept of protein folds is discussed, starting with the
      original concept of super-secondary structure. This has led to the recognition of
      a fairly small number of distinct folds defining individual domains within larger
      proteins. Each fold can usually be associated with a specific function. Thus the
      active site of an enzyme is likely to be at the boundary between domains, each
      contributing a simple function to a more complex process.

PMID- 22987344
TI  - Hierarchical representation of supersecondary structures using a graph
      theoretical approach.
AB  - The unique representation of proteins becomes more and more important with the
      growing number of known protein structure data. Graph-theory provides many
      methods not only for the description but also for comparison and classification
      of protein structures. Here, we describe a graph-theoretical modeling approach of
      the protein supersecondary structure. The resulting linear notations are
      intuitive and can be used to find common substructures very fast and easily. We
      illustrate the necessary definitions by biological examples and discuss the
      representation of various supersecondary structure motifs.

PMID- 22987345
TI  - Up, down, and around: identifying recurrent interactions within and between super
      secondary structures in beta-propellers.
AB  - The examination and analysis of super-secondary structures or other specific
      structural patterns associated with particular functions, sequence motifs, or
      structural contexts require that the set of structures examined shares the same
      feature. This seems obvious but in practice this may often present problems such
      as identifying complete sets of data avoiding false positives. In the case of the
      beta-propeller structures the symmetry of the propeller creates problems for many
      structure similarity search programs. Here we present a procedure that will
      identify propeller structures in PDB and assign them to the different N-propeller
      types. In addition we outline methods to examine similarities and differences
      within and between the four stranded up-and-down blades of the beta-propeller.

PMID- 22987342
TI  - Severe hyperglycemia immediately after allogeneic hematopoietic stem-cell
      transplantation is predictive of acute graft-versus-host disease.
AB  - Stress hyperglycemia and acute graft-versus-host disease (GVHD), the major early
      complication of hematopoietic stem cell transplantation (HSCT), are both
      associated with excessive release of inflammatory cytokines. We investigated
      whether new-onset hyperglycemia immediately after HSCT predicts acute GVHD. We
      studied nondiabetic adult recipients of human leukocyte antigen-matched HSCT
      (peripheral blood stem cells) for acute leukemia. Using mean morning serum
      glucose on Days 1-10, we classified hyperglycemia as: mild (6.11-8.33 mmol/L),
      moderate (8.34-9.98), and severe (minimum of 9.99). Subjects who were GVHD-free
      on Day 10 were followed during Days 11-100 for grades II-IV acute GVHD or
      competing event. Evaluation utilized cumulative incidence-based proportional
      hazards regression. Subjects (n = 328) were age 18-74, median of 49 years. Per
      body mass index (BMI)--25.0 % were obese (BMI, 30-48), 33.8 % overweight (25 to
      <30), 30.8 % normal weight (21 to <25), and 10.4 % lean (18 to <21). Mild,
      moderate, or severe hyperglycemia occurred during Days 1-10 in 50.0, 21.3, and
      16.8 % of subjects, respectively. Cumulative incidence on Day 100 was 44.8 (+/
      2.8) % acute GVHD and 7.9 (+/-1.5) % competing event. Among normal-to-overweight
      subjects (n = 212), severe hyperglycemia developed in 14.2 % (n = 30) and more
      than doubled the risk of acute GVHD (hazards ratio, 2.71; 95 % CI, 1.58-4.65-
      adjusted for donor/recipient characteristics, prophylactic regimen, and
      mucositis). In contrast, among obese subjects (n = 82), severe hyperglycemia
      developed in 30.5 % (n = 25) but did not significantly affect risk of GVHD. (No
      lean subjects (n = 34) developed severe hyperglycemia.) Hyperglycemia that was
      less than severe had an effect indistinguishable from normoglycemia. In
      nondiabetic patients, severe hyperglycemia immediately after allogeneic HSCT
      indicates increased likelihood of acute GVHD. This association is absent in obese
      patients, who may be primed by obesity-induced inflammation to develop severe
      hyperglycemia even without experiencing the cytokine storm that is essential to
      GVHD pathogenesis.

PMID- 22987346
TI  - Structure description and identification using the tableau representation of
      protein folding patterns.
AB  - We have developed a concise tableau representation of protein folding patterns,
      based on the order and contact patterns of elements of secondary structure:
      helices and strands of sheet. The tableaux provide a database, derived from the
      protein data bank, minable for studies on the general principles of protein
      architecture, including investigation of the relationship between local
      supersecondary structure of proteins and the complete folding topology. This
      chapter outlines the tableaux representation of protein folding patterns and
      methods to use them to identify structural and substructural similarities.

PMID- 22987347
TI  - Computational prediction of secondary and supersecondary structures.
AB  - The sequence-based prediction of the secondary and supersecondary structures
      enjoys strong interest and finds applications in numerous areas related to the
      characterization and prediction of protein structure and function. Substantial
      efforts in these areas over the last three decades resulted in the development of
      accurate predictors, which take advantage of modern machine learning models and
      availability of evolutionary information extracted from multiple sequence
      alignment. In this chapter, we first introduce and motivate both prediction areas
      and introduce basic concepts related to the annotation and prediction of the
      secondary and supersecondary structures, focusing on the beta hairpin, coiled
      coil, and alpha-turn-alpha motifs. Next, we overview state-of-the-art prediction
      methods, and we provide details for 12 modern secondary structure predictors and
      4 representative supersecondary structure predictors. Finally, we provide several
      practical notes for the users of these prediction tools.

PMID- 22987348
TI  - A survey of machine learning methods for secondary and supersecondary protein
      structure prediction.
AB  - In this chapter we provide a survey of protein secondary and supersecondary
      structure prediction using methods from machine learning. Our focus is on machine
      learning methods applicable to beta-hairpin and beta-sheet prediction, but we
      also discuss methods for more general supersecondary structure prediction. We
      provide background on the secondary and supersecondary structures that we
      discuss, the features used to describe them, and the basic theory behind the
      machine learning methods used. We survey the machine learning methods available
      for secondary and supersecondary structure prediction and compare them where
      possible.

PMID- 22987349
TI  - Beyond supersecondary structure: the global properties of protein sequences.
AB  - Analysis of the global properties of protein sequences, rather than single-site
      or local properties, has been shown to lead to new understanding of folding and
      function. Here we describe the use of software which can describe sequences
      numerically in an orthonormal fashion, Fourier-analyze those sequences, and
      verify the statistical significance of the resulting Fourier coefficients. The
      resulting parameters can be used to study problems involving sequences from a
      unique perspective.

PMID- 22987350
TI  - Creating supersecondary structures with BuildBeta.
AB  - BuildBeta is a feature of the ProteinShop software designed to thoroughly sample
      a protein conformational space given the protein's sequence of amino acids and
      secondary structure predictions. It targets proteins with beta sheets because
      they are particularly challenging to predict due to the complexity of sampling
      long-range strand pairings. Here we discuss some of the most difficult targets in
      the recent 9th Community Wide Experiment on the Critical Assessment of Techniques
      for Protein Structure Prediction (CASP9) and show how BuildBeta can leverage some
      of the most successful methods in the category "template-free modeling" by
      augmenting their sampling capabilities. We also discuss ongoing efforts to
      improve the quality of the supersecondary structures it generates.

PMID- 22987352
TI  - Residue-residue contacts: application to analysis of secondary structure
      interactions.
AB  - Protein structures and their complexes are formed and stabilized by interactions,
      both inside and outside of the protein. Analysis of such interactions helps in
      understanding different levels of structures (secondary, super-secondary, and
      oligomeric states). It can also assist molecular biologists in understanding
      structural consequences of modifying proteins and/or ligands. In this chapter,
      our definition of atom-atom and residue-residue contacts is described and applied
      to analysis of protein-protein interactions in dimeric beta-sandwich proteins.

PMID- 22987351
TI  - A modular perspective of protein structures: application to fragment based loop
      modeling.
AB  - Proteins can be decomposed into supersecondary structure modules. We used a
      generic definition of supersecondary structure elements, so-called Smotifs, which
      are composed of two flanking regular secondary structures connected by a loop, to
      explore the evolution and current variety of structure building blocks. Here, we
      discuss recent observations about the saturation of Smotif geometries in protein
      structures and how it opens new avenues in protein structure modeling and design.
      As a first application of these observations we describe our loop conformation
      modeling algorithm, ArchPred that takes advantage of Smotifs classification. In
      this application, instead of focusing on specific loop properties the method
      narrows down possible template conformations in other, often not homologous
      structures, by identifying the most likely supersecondary structure environment
      that cradles the loop. Beyond identifying the correct starting supersecondary
      structure geometry, it takes into account information of fit of anchor residues,
      sterical clashes, match of predicted and observed dihedral angle preferences, and
      local sequence signal.

PMID- 22987353
TI  - Super-secondary structures and modeling of protein folds.
AB  - A characteristic feature of the polypeptide chain is its ability to form a
      restricted set of commonly occurring folding units composed of two or more
      elements of secondary structure that are adjacent along the chain. Some of these
      super-secondary structures exhibit a unique handedness and a unique overall fold
      irrespective of whether they occur in homologous or nonhomologous proteins. Such
      super-secondary structures are of particular value since they can be used as
      starting structures in protein modeling. The larger protein folds can be obtained
      by stepwise addition of other secondary structural elements to the starting
      structures taking into account a set of simple rules inferred from known
      principles of protein structure.

PMID- 22987354
TI  - Computational simulations of protein folding to engineer amino acid sequences to
      encourage desired supersecondary structure formation.
AB  - The dynamics of protein folding are complicated because of the various types of
      amino acid interactions that create secondary, supersecondary, and tertiary
      interactions. Computational modeling can be used to simulate the biophysical and
      biochemical interactions that determine protein folding. Effective folding to a
      desired protein configuration requires a compromise between speed, stability, and
      specificity. If the primary sequence of amino acids emphasizes one of these
      characteristics, the others might suffer and the folding process may not be
      optimized. We provide an example of a model peptide whose primary sequence
      produces a highly stable supersecondary two-helix bundle structure, but at the
      expense of lower speed and specificity of the folding process. We show how
      computational simulations can be used to discover the configuration of the
      kinetic trap that causes the degradation in the speed and specificity of folding.
      We also show how amino acid sequences can be engineered by specific substitutions
      to optimize the folding to the desired supersecondary structure.

PMID- 22987355
TI  - Protein folding at atomic resolution: analysis of autonomously folding
      supersecondary structure motifs by nuclear magnetic resonance.
AB  - The study of protein folding has been conventionally hampered by the assumption
      that all single-domain proteins fold by an all-or-none process (two-state
      folding) that makes it impossible to resolve folding mechanisms experimentally.
      Here we describe an experimental method for the thermodynamic analysis of protein
      folding at atomic resolution using nuclear magnetic resonance (NMR). The method
      is specifically developed for the study of small proteins that fold autonomously
      into basic supersecondary structure motifs, and that do so in the sub-millisecond
      timescale (folding archetypes). From the NMR experiments we obtain hundreds of
      atomic unfolding curves that are subsequently analyzed leading to the
      determination of the characteristic network of folding interactions. The
      application of this approach to a comprehensive catalog of elementary folding
      archetypes holds the promise of becoming the first experimental approach capable
      of unraveling the basic rules connecting protein structure and folding mechanism.

PMID- 22987356
TI  - Artificial supersecondary structures based on aromatic oligoamides.
AB  - With an intelligent design of the monomers, considerable effort has so far
      focused on the creation of aromatic oligoamide foldamers which are able to mimic
      the secondary structures of biopolymers. Supersecondary structure is a growing
      set of known and classifiable protein folding patterns that provides an important
      organizational context to this complex endeavor. In this article, we highlight
      the design, chemical synthesis, and structural studies of artificial
      supersecondary structures based on aromatic oligoamide foldamers in recent years.

PMID- 22987357
TI  - Cross-beta-sheet supersecondary structure in amyloid folds: techniques for
      detection and characterization.
AB  - The formation of protein aggregates is linked to the onset of several human
      disorders of increasing prevalence, ranging from dementia to diabetes. In most of
      these diseases, the toxic effect is exerted by the self-assembly of initially
      soluble proteins into insoluble amyloid-like fibrils. Independently of the
      protein origin, all these macromolecular assemblies share a common supersecondary
      structure: the cross-beta-sheet conformation, in which a core of beta-strands is
      aligned perpendicularly to the fibril axis forming extended regular beta-sheets.
      Due to this ubiquity, the presence of cross-beta-sheet conformational signatures
      is usually exploited to detect, characterize, and screen for amyloid fibrils in
      protein samples. Here we describe in detail some of the most commonly used
      methods to analyze such supersecondary structure.

PMID- 22987358
TI  - Analyzing oligomerization of individual transmembrane helices and of entire
      membrane proteins in E. coli: A hitchhiker's guide to GALLEX.
AB  - Genetic systems, which allow monitoring interactions of individual transmembrane
      alpha-helices within the cytoplasmic membrane of the bacterium Escherichia coli,
      are now widely used to probe the structural biology and energetics of helix-helix
      interactions and the consequences of mutations. In contrast to other systems, the
      GALLEX system allows studying homo- as well as heterooligomerization of
      individual transmembrane alpha-helices, and even enables estimation of the
      energetics of helix-helix interactions within a biological membrane. Given that
      many polytopic membrane proteins form oligomers within membranes, the GALLEX
      system represents a unique and powerful approach to monitor formation and
      stability of oligomeric complexes of polytopic membrane proteins in vivo.

PMID- 22987359
TI  - Supersecondary structure prediction of transmembrane beta-barrel proteins.
AB  - We introduce a graph-theoretic model for predicting the supersecondary structure
      of transmembrane beta-barrel proteins--a particular class of proteins that
      performs diverse important functions but it is difficult to determine their
      structure with experimental methods. This ab initio model resolves the protein
      folding problem based on pseudo-energy minimization with the aid of a simple
      probabilistic filter. It also allows for determining structures whose barrel
      follows a given permutation on the arrangement of beta-strands, and allows for
      rapidly discriminating the transmembrane beta-barrels from other kinds of
      proteins. The model is fairly accurate, robust and can be run very efficiently on
      PC-like computers, thus proving useful for genome screening.

PMID- 22987360
TI  - Functional structural motifs for protein-ligand, protein-protein, and protein
      nucleic acid interactions and their connection to supersecondary structures.
AB  - Protein functions are mediated by interactions between proteins and other
      molecules. One useful approach to analyze protein functions is to compare and
      classify the structures of interaction interfaces of proteins. Here, we describe
      the procedures for compiling a database of interface structures and efficiently
      comparing the interface structures. To do so requires a good understanding of the
      data structures of the Protein Data Bank (PDB). Therefore, we also provide a
      detailed account of the PDB exchange dictionary necessary for extracting data
      that are relevant for analyzing interaction interfaces and secondary structures.
      We identify recurring structural motifs by classifying similar interface
      structures, and we define a coarse-grained representation of supersecondary
      structures (SSS) which represents a sequence of two or three secondary structure
      elements including their relative orientations as a string of four to seven
      letters. By examining the correspondence between structural motifs and SSS
      strings, we show that no SSS string has particularly high propensity to be found
      interaction interfaces in general, indicating any SSS can be used as a binding
      interface. When individual structural motifs are examined, there are some SSS
      strings that have high propensity for particular groups of structural motifs. In
      addition, it is shown that while the SSS strings found in particular structural
      motifs for nonpolymer and protein interfaces are as abundant as in other
      structural motifs that belong to the same subunit, structural motifs for nucleic
      acid interfaces exhibit somewhat stronger preference for SSS strings. In regard
      to protein folds, many motif-specific SSS strings were found across many folds,
      suggesting that SSS may be a useful description to investigate the universality
      of ligand binding modes.

PMID- 22987362
TI  - Segmental myocardial velocities in dilated cardiomyopathy with and without left
      bundle branch block.
AB  - PURPOSE: To quantify three-directional left ventricular (LV) myocardial
      velocities and intraventricular synchrony in dilated cardiomyopathy (DCM) with
      and without left bundle branch block (LBBB) using MR tissue phase mapping (TPM).
      MATERIALS AND METHODS: Regional velocities were assessed by TPM (spatial/temporal
      resolution = 1.3 * 1.3 mm(2) * 8 mm/14 ms) in DCM patients with (n = 12) and
      without LBBB (n = 7) compared with age-matched volunteers (n = 20). For the
      evaluation the AHA 16-segment and an extended LV visualization model was used.
      RESULTS: Radial velocities in DCM patients were reduced in 75% (systole) and in
      94% (diastole) (P = 0.0001 - P = 0.0360), long-axis velocities in 31% (systole)
      and in 75% (diastole) of the 16 segments compared with controls (P = 0.0001 - P =
      0.0310). LBBB resulted in inferolaterally delayed diastolic long-axis velocities
      (P = 0.0012 - P = 0.0464) and shortened TTP for septal systolic radial velocities
      (P = 0.0002). Intra-ventricular radial systolic TTP differed up to 150 ms between
      segments in patients with LBBB (89 ms without LBBB, 34 ms in volunteers)
      reflecting an increased dyssynchrony. LV twist was altered in all patients with
      reduced and delayed systolic and diastolic peak velocities. CONCLUSION: TPM
      identified previously not described alterations of the spatial distribution and
      timing of all myocardial velocities in patients with DCM and LBBB. This may help
      to optimize therapy management in future.

PMID- 22987361
TI  - Endothelial P2X7 receptors' expression is reduced by schistosomiasis.
AB  - Endothelial cells control vascular tone, permeability and leukocyte
      transmigration and are modulated by pro-inflammatory mediators. Schistosomiasis
      is an intravascular disease associated with inflammation, therefore altering
      endothelial cells' phenotype. Purinergic P2X7 receptors (P2X7R) play an important
      role in inflammation; however, the impact of the disease upon endothelial P2X7R
      function or expression has not been explored. Using ethidium bromide uptake to
      investigate P2X7R function, we observed that the effects of ATP (3 mM) and the
      P2X7R agonist 3'-O-(4-benzoyl)-ATP (BzATP) were smaller in mesenteric endothelial
      cells from the Schistosoma mansoni-infected group than in the control group. In
      the control group, BzATP induced endothelial nitric oxide production, which was
      blocked by the P2X7R antagonists KN-62 and A740003. However, in the infected
      group, we observed a reduced effect of BzATP and no effect of both P2X7R
      antagonists, suggesting a downregulation of endothelial P2X7R in schistosomiasis.
      We observed similar results in both infected and P2X7R(-/-) groups, which were
      also comparable to data obtained with KN-62- or A740004-treated control cells.
      Data from Western blot and immunocytochemistry assays confirmed the reduced
      expression of P2X7R in the infected group. In conclusion, our data show a
      downregulation of P2X7R in schistosomiasis infection, which likely limits the
      infection-related endothelial damage.

PMID- 22987363
TI  - Regulation of UHMWPE biomaterials in total hip arthroplasty.
AB  - This manuscript provides a brief history of the development of ultrahigh
      molecular weight polyethylene (UHWMPE) biomaterials and how the U.S. Food and
      Drug Administration (FDA) regulates medical devices. The flowchart used to decide
      whether a device is medium or high risk, known as the 510(k) flowchart, is
      illustrated by taking several examples through the flowchart. In order to
      demonstrate how changes to UHWMPE material used in the acetabular liners of total
      hips have been regulated, two major modifications to UHMWPE, highly crosslinked
      polyethylene and Vitamin E polyethylene, are taken through the flowchart. This
      manuscript describes the testing that has been provided to demonstrate safety and
      effectiveness of these modifications, as well as an explanation why the testing
      was supplied to the FDA.

PMID- 22987364
TI  - Combined analysis of three Lynch syndrome cohorts confirms the modifying effects
      of 8q23.3 and 11q23.1 in MLH1 mutation carriers.
AB  - Two colorectal cancer (CRC) susceptibility loci have been found to be
      significantly associated with an increased risk of CRC in Dutch Lynch syndrome
      (LS) patients. Recently, in a combined study of Australian and Polish LS
      patients, only MLH1 mutation carriers were found to be at increased risk of
      disease. A combined analysis of the three data-sets was performed to better
      define this association. This cohort-study includes three sample populations
      combined totaling 1,352 individuals from 424 families with a molecular diagnosis
      of LS. Seven SNPs, from six different CRC susceptibility loci, were genotyped by
      both research groups and the data analyzed collectively. We identified
      associations at two of the six CRC susceptibility loci in MLH1 mutation carriers
      from the combined LS cohort: 11q23.1 (rs3802842, HR = 2.68, p <= 0.0001)
      increasing risk of CRC, and rs3802842 in a pair-wise combination with 8q23.3
      (rs16892766) affecting age of diagnosis of CRC (log-rank test; p <= 0.0001). A
      significant difference in the age of diagnosis of CRC of 28 years was observed in
      individuals carrying three risk alleles compared to those with 0 risk alleles for
      the pair-wise SNP combination. A trend (due to significance threshold of p <=
      0.0010) was observed in MLH1 mutation carriers towards an increased risk of CRC
      for the pair-wise combination (p = 0.002). This study confirms the role of
      modifier loci in LS. We consider that LS patients with MLH1 mutations would
      greatly benefit from additional genotyping of SNPs rs3802842 and rs16892766 for
      personalized risk assessment and a tailored surveillance program.

PMID- 22987365
TI  - The impact of sialic acids on the pharmacokinetics of a PEGylated erythropoietin.
AB  - Erythropoietin (EPO) is an important molecule in the erythropoiesis and various
      forms of EPO have been marketed in managing anemia in humans. Long acting EPOs
      for less frequent dosing have been generated either by increasing the number of
      glycosylation sites of the EPO molecule or by linking it to a polyethylene glycol
      (PEG). We have generated recombinant human EPO (rhEPO) using glycoengineered
      Pichia pastoris strains and evaluated the pharmacokinetics (PK) in rats of this
      molecule linked to a 40 kDa PEG (PEGylated rhEPO), in relation to its
      glycosylation patterns. As expected, the PEGylated rhEPO exhibited a significant
      improvement in half-life of serum when compared with the non-PEGylated version.
      Interestingly, the PK properties of the PEGylated rhEPO molecule were also
      significantly influenced by the glycosylation profile. Specifically, PEGylated
      rhEPO with a significantly higher sialic acid content in the biantennary
      structure (high A2) exhibited lower systemic clearance and higher systemic
      exposure than those with a lower sialic acid content (low A2) following either
      intravenous or subcutaneous administrations. These results suggest that A2
      content may be one of the important criteria for release in manufacturing
      PEGylated rhEPO to ensure consistent PK.

PMID- 22987367
TI  - Value of the electrocardiographic signs in differential diagnosis of
      atrioventricular nodal reentrant tachycardia.

PMID- 22987366
TI  - Potential therapeutic target and independent prognostic marker of TROP2 in
      laryngeal squamous cell carcinoma.
AB  - BACKGROUND: The human trophoblastic cell surface antigen 2 (TROP2) gene is
      associated with the development of malignancies, but its expression in laryngeal
      squamous cell carcinoma (SCC) and its relationship with clinical characteristics
      of the disease remain undetermined. METHODS: Expression of TROP2 protein was
      detected by immunohistochemistry with a self-made anti-TROP2 antibody in
      laryngeal SCC tissue microarrays. RESULTS: Elevated expression of TROP2 was
      detected in laryngeal SCC tissues compared with adjacent noncancerous tissues.
      TROP2 expression in laryngeal SCC was related to tumor differentiation (p =
      .0001) and lymph node metastasis (p = .0352). Cox regression analyses confirmed
      that TROP2 expression (p = .015), lymph node metastasis (p = .001), degree of
      differentiation (p = .002), tumor site (p = .021), and T classification (p =
      .003) were independent prognostic factors. CONCLUSIONS: TROP2 can be used as an
      independent prognostic indicator for laryngeal SCC.

PMID- 22987368
TI  - DFT and experimental determination of conformations of 2-(ethoxycarbonylmethoxy)
      5-(arylazo)benzaldehydes and their oximes.
AB  - 2-(Ethoxycarbonylmethoxy)-5-(arylazo)benzaldehydes 1-4 and their oximes 5-8 were
      synthesized and characterized by IR, (1)H and (13)C NMR spectroscopy. The
      favoured conformations of aldehydes 1-4 and oximes 5-8 were predicted
      theoretically. Selected geometrical parameters and charges were derived from
      optimized structures. IR, (1)H and (13)C NMR data were also computed using
      Gaussian-03 package and compared with the observed values. (15)N and (17)O
      chemical shifts were also determined theoretically.

PMID- 22987369
TI  - [Fatal complication of hyperemesis gravidarum: Wernicke's encephalopathy].

PMID- 22987370
TI  - Laparoscopic diagnosis and treatment of an acute epiploic appendagitis.

PMID- 22987371
TI  - [Atypical presentations of internal mammary chain involvement in breast cancer].
AB  - BACKGROUND: Breast cancer is the first cancer in women. Lymphatic involvement in
      breast cancer is common, especially in our patients because of the frequency of
      locally advanced forms. This contrast with a weak rate of diagnosed internal
      mammary chain invasion. METHODS: We present observations of patients presenting
      atypical forms of internal mammary chain involvement. AIM: To clarify the
      atypical presentations of internal mammary chain involvement in breast cancer.
      RESULTS: The invasion of internal mammary chain is often underestimated. Indeed,
      this site of lymphatic spread is not accessible to the clinical exam and its
      radiological exploration is not systematic. Otherwise, different clinical,
      pathological and radiological presentations have to attract our attention to a
      potential internal mammary chain invasion. CONCLUSION: Our misrecognition of this
      site of spread and its different presentations can partly explain the lack of
      diagnosis.

PMID- 22987372
TI  - [Nocturnal gastroesophageal reflux and sleep apnea: what relationship?].
AB  - BACKGROUND: Gastroesophageal reflux disease and nocturnal sleep disturbances are
      frequently encountered in clinical practice and are often associated. However,
      the combination of these two syndromes does not necessarily imply a cause and
      effect. In a more precise, the relationship between nocturnal gastroesophageal
      reflux and sleep apnea syndrome has been debated since even if their respective
      prevalences are high in the presence of one or the other syndrome, it is
      difficult to eliminate mutual induction. AIM: To determine the pathophysiological
      relations, the frequency of the association between nocturnal gastroesophageal
      reflux and sleep apnea syndrome and the impact of specific therapies to each of
      these two syndromes on the other. METHODS: Review of the literature. RESULTS: On
      the relationship between these two entities, it seems obvious that nocturnal
      gastroesophageal reflux affects the normal physiology of sleep and alters its
      quality and that the sleep apnea syndrome can aggravate reflux. On the frequency
      of their association, gastroesophageal reflux was observed in the presence of
      sleep apnea syndrome; in 27 to 75% of patients in studies that do not include pH
      metric and polysomnographic recording simultaneously. Regarding treatment,
      continuous positive airway pressure seems to improve night time gastroesophageal
      reflux both in terms of symptoms that pH-metric results. Similarly, inhibitors of
      proton pump inhibitors have demonstrated their effectiveness in combination with
      specific treatment, in improving symptoms caused by sleep apnea syndrome.
      CONCLUSION: we can confirm that there is a strong link between nocturnal
      gastroesophageal reflux and sleep apnea syndrome but causality is hard to be
      confirmed. Moreover, it seems useful to look for sleep disorders in patients with
      nocturnal gastroesophageal reflux also to suggest the diagnosis of
      gastroesophageal reflux in patients with sleep apnea syndrome.

PMID- 22987373
TI  - [Immunophenotyping in adult acute myeloid leukemia: which prognostic value?].
AB  - BACKGROUND: Immunophenotyping is an essential step in the diagnosis of acute
      myeloid leukemia. Its prognostic value remains controversial with contradictory
      results. AIM: To assess prognostic impact of the immunophenotyping in AML.
      METHODS: Our study is retrospective (October, 2005 - July, 2007) concerning 56
      cases of AML (AML3 excluded) of the adult from 18 to 55 years old diagnosed and
      treated in Tunis Aziza Othmana Hospital. The immunophenotyping was performed by
      flow cytometry (Beckman Coulter EPICS XL MCL(r)). We studied clinical and
      biological characteristic, immunophenotypic expressions, and parameters of the
      response to the treatment: complete remission (CR), overall survival (OS),
      relapse free survival (RFS) and relapse in a delay of 1 year and 2 years. SPSS
      software was used to perform the statistical analysis. RESULTS: The median age of
      the patients is of 37,7+/-11.8 years. Sex ratio (M/F) is 1.33. Among individual
      antigenic expressions, only CD7 is associated to lower CR rates (p=0.044). We did
      not find any statistically significant association between immunophenotypic
      expressions and OS nor with relapse or RFS. CONCLUSION: The impact of
      immunophenotyping in AML remains controversial because of contradictory results.
      The research of molecular changes would be an interesting alternative in our
      context.

PMID- 22987374
TI  - [Pregnancy in dermatomyositis and polymyositis].
AB  - AIM: To determine the incidence of pregnancies during the inflammatory myopathy
      (IM), its influence on this disease and the influence of IM on the pregnancy's
      outcome. METHODS: From 1979 to 2007 we have collected retrospectively 67cases of
      IM (53 women and 14 men) in the department of internal medicine CHU Hedi Chaker
      of Sfax (Tunisia). Diagnosis criteria were those and Peter. We have included
      pregnancies occurring after diagnosis of DM or PM and cases of IM occurring
      during pregnancy or postpartum. RESULTS: Five women (4DM and PM), average age
      30.6 years (range 26 - 41 years) conducted 10 pregnancies (9.4%). The fertility
      rate is 2 pregnancies per patient. Nine pregnancies occurred after the diagnosis
      of myositis in 4 women. IM was inactive at conception in all this cas.No flare-up
      in IM has been noted during these pregnancies. The DM was revealed to the 10th
      day post-partum in one patient. Therapeutic interruption of pregnancy was needed
      in 3 cases. 4 pregnancies were completed without incident and resulted in the
      birth of healthy newborns. Foetal complications were observed in the other two
      pregnancies occurring in one patient who also presents an APS associated with DM.
      It was a foetal death in utero and premature delivery of a newborn who died in
      3rd day after birth. CONCLUSION: Pregnancy in the MI is rare. Its influence on
      the activity of the disease is variable, both during the pregnancy than
      postpartum. The foetal prognosis is good when the the disease is in remission.
      However foetal complications are important in case of active IM.

PMID- 22987375
TI  - Testicular cancer patterns in Tunisian men : diagnosis problems, pathological
      types and prognosis. About 41 patients.
AB  - AIM: To analyze the testicular cancer (TCa) incidence, diagnosis aspects,
      pathologic grade, stage, and survival in Tunisian men. METHODS: We studied all
      patients who had histopathologically confirmed TCa treated in La Rabta University
      Hospital between 1991 and 2010. Baseline demographic data included age at
      diagnosis, year of diagnosis, clinical symptoms, stage at diagnosis, histologic
      type, management strategies and survival were analyzed. RESULTS: The incidence of
      TCa among Tunisians is very low; we collected only 41 cases over a period of 20
      years with an average incidence of 2 new cases per year. Peak age incidence was
      30-49 years. Testicular swelling was the principal complaint in 25 patients.
      58.5% of tumours were rightsided and 39% were left-sided. There was bilateral
      involvement in only one case. The mean interval between onset of symptoms and
      presentation was 16.5 months (1-120). Most patients presented at stages T2 and T3
      (63.4% and 26.8% respectively). Treatment consisted of radical orchidectomy in
      all patients and cisplatin-based chemotherapy and radiotherapy in respectively 11
      and 12 patients (association in 5 patients). One patient with a tumour in an
      intra-abdominal testis underwent laparotomy. The most common histological types
      were seminomas (n=20) and mixed germ cell (n=8). Three patients died within 48
      months, while half were lost to follow-up. CONCLUSIONS: The incidence of TCas in
      Tunisia remains low. Late presentation and treatment are major challenges to
      management. Better health funding and education regarding testicular self
      examination is essential.

PMID- 22987376
TI  - Lack of association between C3123A polymorphism of the angiotensin II type 2
      receptor gene and hypertension in Tunisian population.
AB  - BACKGROUND: Hypertension is a polygenic disease. Various singlenucleotide gene
      polymorphisms of renin angiotensin system have been explored in hypertension.
      Angiotensin II, the major biologically active component of this system, exerts
      its effect via two pharmacologically distinct subtypes of angiotensin II
      receptors, the angiotensin II type 1 receptor and the angiotensin II type 2
      receptor. AIM: To examine whether the 3123 C/A polymorphism of angiotensin II
      type 2 receptor gene is involved in hypertension in a sample of Tunisian
      population. METHODS: Atotal of 403 normotensive subjects and 382 hypertensive
      patients were included in the study. Genotyping was performed by polymerase chain
      reaction followed by Alu I restriction digestion. RESULTS: The frequency of "A"
      genotype was not significantly different between the two groups in men (-2=1.18;
      p=0.16). The estimated odds prevalence for hypertension ("A" versus "C") was 0.77
      (95% CI 0.49 to 1.22, p=0.27). After adjustment for confounding factors, the OR
      for hypertension remained no significant (OR: 1.49, 95% CI: 0.84-2.63, p=0.16).
      In women, genotype distributions for C3123A variant in hypertensive patients were
      not significantly different from normotensive subjects (-2=3.16; p=0.20).
      Multiple logistic regression analysis showed that the AA genotype was not
      significantly associated with hypertension (OR: 1.09, 95% CI: 0.58-2.06, p=0.77).
      CONCLUSION: In the present study, we showed that the 3123 C/A polymorphism of
      AGT2R gene is not a significant factor for hypertension in a sample of Tunisian
      population.

PMID- 22987377
TI  - [Emergency peripartum hysterectomy: indications and prognosis].
AB  - AIM: Detect the risk factors, indications and maternal morbidity of haemostatic
      hysterectomy. METHODS: A retrospective study of 46 women who had haemostatic
      hysterectomy between 2005 and 2009. RESULTS: The mean age was 33.3 years. The
      mean parity was 3.5. 35% of patients had a previous cesarean section. The mode of
      delivery was: vaginal delivery (47.8%), cesarean delivery (52.2 %). The
      hysterectomy was subtotal in 39 cases (85%). The indications of haemostatic
      hysterectomy was: uterine inertia (44%), disseminated intravascular coagulation
      (26%), placenta accreta (8.7%), Placenta praevia (13%), uterine rupture
      (8.7%).Three patients were dead. Five patients had a depression. Six patients had
      a dyspareunia. Five patients had a decrease of sexual desire. CONCLUSION:
      Haemostatic hysterectomy is a mutilating surgery giving an irreversible
      infertility. The development of arterial embolization avoid the appeal to this
      surgery.

PMID- 22987378
TI  - [The Caroli's disease. Report of 16 cases].
AB  - BACKGROUND: Caroli's disease is a congenital dilatation of the intrahepatic
      biliary duct. AIM: To analyse and discuss diagnostic and therapeutics
      difficulties through 16 patients with Caroli's disease. METHODS: Between January
      1990 and September 2010, 16 patients underwent surgical procedure for Caroli's
      disease. Data recorded for each patient included clinical symptoms, biologic
      findings, previous biliary procedures, and the presenting symptoms. The
      distribution of the biliary lesions, the surgical procedure and the postoperative
      outcomes and follow up were detailed. RESULTS: The mean age was 55 years. The
      mean interval between the first symptoms and diagnosis was 27 months. Five of 16
      patients had undergone 12 surgical or endoscopic procedures prior to liver
      resection. Before the definitive diagnosis, 9 patients presented 15 episodes of
      acute cholangitis. The diagnosis was established preoperatively in 13 cases, 5
      among them underwent previous biliary surgical procedures. The diagnosis was
      documented peroperatively in 2 cases and postoperatively in 1 case. The
      distribution of the biliary lesions was monolobar in 13 and bilobar in 3
      patients. 13 patients underwent liver resection, in two cases we perfomed
      biliojejunostomy and the last one had endoscopic sphincterotomy. There was no
      mortality and the overall postoperative morbidity is about 43%. The follow-up
      shows that 12 patients still alive with a mean follow up for 53 months, from whom
      only one patient have intrahepepatic lithiasis. CONCLUSION: The clinical course
      of Caroli's disease is often complicated by recurrent episodes of angiocholitis
      and requires iterative surgery. The hepatectomy witch prevented septic
      complications and degenerescence is possible only in a restricted number of
      patients.

PMID- 22987379
TI  - [Vasculitis in Sweet's Syndrome].
AB  - BACKGROUND: Also called acute febrile neutrophilic dermatosis, Sweet's syndrome
      is non-infective dermatoses that exhibit a predominantly neutrophilic
      inflammatory infiltrate. Absence of vasculitis is a histologic criterion for
      diagnosis. However, recent reports suggest that vasculitis should not exclude the
      diagnosis. AIM: To describe their clinical, pathological and therapeutic
      characteristics. METHODS: We report a series of 47 cases of Sweet's syndrome,
      collected in our institution between 1997 and 2011. RESULTS: The patient
      population consisted of 11 males and 36 females. The mean age was 47 years (28
      74). An associated disease process was seen in 10 patients: inflammatory disease
      (3 cases), inflammatory bowel disease (2 cases), tuberculosis (3 cases) and
      diabetes (3 cases). One case of pregnancy was observed. In the prodromal phase,
      functional symptoms were reported in 38 cases (80.8%). Cutaneous lesions
      consisted of erythematous plaques or nodules. Lesions were located mainly on the
      upper or lower extremities. All biopsy specimens demonstrated a dermal infiltrate
      composed predominantly of neutrophils. Fibrinoid necrosis and intramural
      inflammation were observed in 8 cases. CONCLUSION: The dermatosis can precede,
      follow, or appear concurrent with the diagnosis of the patient's diseases which
      requires careful surveillance.

PMID- 22987380
TI  - [Special features of systemic sclerosis in men].
AB  - BACKGROUND: Systemic sclerosis (SS) is a generalized disorder of connective
      tissue and microvasculature characterized by tissue fibrosis and obliteration of
      the vessels. Several features of systemic scleroderma in men are discussed in the
      literature. AIM: To investigate the initial clinical features, evolution and
      prognosis of systemic sclerosis in men. METHODS: Patients with systemic sclerosis
      based on ACR's criteria were included. In this retrospective study we compared a
      cohort of men to a cohort of women, diagnosed between 2000 and 2010 in department
      of internal medicine. RESULTS: Fifty four patients were included amongst which
      nine men. The mean follow-up duration was 39.5 months. A higher proportion of
      cardiac, renal and lung involvement were noted at diagnosis Localized cutaneous
      sclerosis was predominant in men. CONCLUSION: This work has highlighted several
      features of systemic sclerosis encountered in men. These results warrant
      confirmation by analyzing a larger population.

PMID- 22987381
TI  - Evaluation of microsatellite instability, MLH1 expression and hMLH1 promoter
      hypermethylation in colorectal carcinomas among Tunisians patients.
AB  - BACKGROUND: About 10% to 15% of sporadic colorectal cancers demonstrate high
      level of microsatellite instability that is generally associated with aberrant
      methylation of hMLH1 promoter. AIM: To investigate the association between MSI
      status, hMLH1 protein expression and methylation status of the hMLH1 promoter in
      a cohort of Tunisian sporadic colorectal cancer. METHODS: Expression of MLH1 and
      MSH2 was determined by immunohistochemistry and the MSI status was analysed by
      microfluid-based on-chip electrophoresis. Methylation of the hMLH1 gene promoter
      was determined by methylation-specific PCR. RESULTS: Of the 150 colorectal
      cancers 57% were MSS, 28% were MSI-L and 15%were MSI-H. MSI-H tumors were more
      frequently right-sided, exhibited a stage III of TNM and tended more to be
      mucinous. The MSI status had no effect on overall patient survival. Most of the
      MSS/MSI-L 79% cancers were unmethylated at the hMLH1 promoter, while 26% MSI-H
      cancers were unmethylated. 84% of MSS and MSI-L expressed MLH1 and 52% of MSI-H
      expressed MLH1. Of the methylated MSI-H cases, 35% expressed MLH1 protein while
      100% of the unmethylated MSI-H were positive for MLH1 staining. Of 11 MSI-H
      cancers with loss of MLH1 expression, all cases were also methylated while 50%
      MSI-H cancers with positive immunostaining for MLH1 were methylated at the hMLH1
      promoter. CONCLUSION: Our study showed that MSI-H phenotype was mucinous, right
      side and exhibit stade III of TNM. The relative correlation of MLH1 expression
      and promotor hypermethylation of hMLH1 for the MSI status is similar to that
      reported for several study.

PMID- 22987382
TI  - [Aspects of myocardic parameters of Tunisian handball players: an
      echocardiographic study].
AB  - BACKGROUND: Given that handball is a mixed sports activity requiring 3 energy
      systems, namely aerobic, anaerobic alactic and lactic, it supposes then a cavity
      dilatation for the efforts involving endurance and a parietal hypertrophy for the
      efforts involving anaerobic work. AIM: To obtain, using the echocardiographic
      method, myocardic measurements from 3 groups of Tunisian handball players of
      different ages, in order to define the myocardic predispositions of the young
      players and to define the morphodynamic adaptation of the heart of the adult
      players so that the impact of the specialty on the operation and the morphology
      of the heart can be better explained. METHODS: Two-dimensional and time motion
      (T.M.) echocardiography (using a TOSHIBA SSH 104 A) was conducted to examine the
      following parameters: diastolic and systolic diameters of the left ventricle, the
      root of the aorta, the left atrium and the right ventricle, as well as the mean
      velocity of the shortening of circumferential fibers, the ejection time of left
      ventricle, and the dimensions of the inter-ventricular septum and the posterior
      wall as well as the E/A ratio. The echocardiograms were performed by medical
      technicians and reviewed by physicians. Thirty six handball players were involved
      in this study. Height and weight of all players were measured before the medical
      test. RESULTS: The Obtained results enable us to advance that the loads of drive
      and competition in handball requested the increase in the parameters of
      dilatation in the young players of 11-12 years to 15-16 years, whereas
      parameterize them of hypertrophy improved thereafter. What justifies the idea,
      which says that in the young players work must be based primarily on the
      improvement of aerobic quality requesting the dilatation of the myocardium,
      thereafter one can consider anaerobic work. CONCLUSION: The practice of handball
      at an early age may induce both cavity dilatation and parietal hypertrophy. The
      long-term consequences and significance of this marked remodeling of the
      athlete's heart is not known.

PMID- 22987383
TI  - [Ovarian pregnancy].

PMID- 22987384
TI  - [Renal disease in infective endocarditis].

PMID- 22987385
TI  - [Fetal ovarian cyst].

PMID- 22987386
TI  - [Urinary bladder gossypiboma in a child].

PMID- 22987387
TI  - [Pancreatic insulinoma].

PMID- 22987388
TI  - [Papillary serous adenocarcinoma of the endometrium and ovary].

PMID- 22987389
TI  - [Cerebral venous thrombosis and ulcerative colitis].

PMID- 22987390
TI  - [Pulmonary amyloidosis].

PMID- 22987391
TI  - Oxidative pyrolysis of polystyrene into styrene monomers in an autothermal fixed
      bed catalytic reactor.
AB  - Styrene monomer recovery: A selective stream of styrene from fast pyrolysis of
      polystyrene is obtained with an autothermal fixed-bed reactor containing noble
      metal (Rh, Pt) catalysts. Autothermal fast pyrolysis of polystyrene is an
      efficient means of recovering monomers from waste polystyrene in a continuous,
      high-throughput process without external heating.

PMID- 22987392
TI  - Changes in the astrocytic aquaporin-4 and inwardly rectifying potassium channel
      expression in the brain of the amyotrophic lateral sclerosis SOD1(G93A)  rat
      model.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      affecting upper and lower motor neurons. Dysfunction and death of motor neurons
      are closely related to the modified astrocytic environment. Astrocytic endfeet,
      lining the blood-brain barrier (BBB), are enriched in two proteins, aquaporin-4
      (AQP4) and inwardly rectifying potassium channel (Kir) 4.1. Both channels are
      important for the maintainance of a functional BBB astrocytic lining. In this
      study, expression levels of AQP4 and Kir4.1 were for the first time examined in
      the brainstem and cortex, along with the functional properties of Kir channels in
      cultured cortical astrocytes of the SOD1(G93A) rat model of ALS. Western blot
      analysis showed increased expression of AQP4 and decreased expression of Kir4.1
      in the brainstem and cortex of the ALS rat. In addition, higher immunoreactivity
      of AQP4 and reduced immunolabeling of Kir4.1 in facial and trigeminal nuclei as
      well as in the motor cortex were also observed. Particularly, the observed
      changes in the expression of both channels were retained in cultured astrocytes.
      Furthermore, whole-cell patch-clamp recordings from cultured ALS cortical
      astrocytes showed a significantly lower Kir current density. Importantly, the
      potassium uptake current in ALS astrocytes was significantly reduced at all
      extracellular potassium concentrations. Consequently, the Kir-specific Cs(+)- and
      Ba(2+)-sensitive currents were also decreased. The changes in the studied
      channels, notably at the upper CNS level, could underline the hampered ability of
      astrocytes to maintain water and potassium homeostasis, thus affecting the BBB,
      disturbing the neuronal microenvironment, and causing motoneuronal dysfunction
      and death.

PMID- 22987393
TI  - Reprogramming of the MHC-I and its regulation by NFkappaB in human-induced
      pluripotent stem cells.
AB  - The immunogenicity of human pluripotent stem cells plays a major role in their
      potential use in the clinic. We show that, during their reprogramming, human
      induced pluripotent stem (iPS) cells downregulate expression of human leukocyte
      antigen (HLA)-A/B/C and beta2 microglobulin (beta2M), the two components of major
      histocompatibility complex-I (MHC-I). MHC-I expression in iPS cells can be
      restored by differentiation or treatment with interferon-gamma (IFNgamma). To
      analyze the molecular mechanisms that regulate the expression of the MHC-I
      molecules in human iPS cells, we searched for correlation between the expression
      of HLA-A/B/C and beta2M and the expression of transcription factors that bind to
      the promoter of these genes. Our results show a significant positive correlation
      between MHC-I expression and expression of the nuclear factors, nuclear factor
      kappa B 1 (NFkappaB1) and RelA, at the levels of RNA, protein and was confirmed
      by chromatin binding. Concordantly, we detected robust levels of NFkappaB1 and
      RelA proteins in the nucleus of somatic cells but not in the iPS cell derived
      from them. Overexpression of NFkappaB1 and RelA in undifferentiated pluripotent
      stem cells led to induction in expression of MHC-I, whereas silencing NFkappaB1
      and RelA by small hairpin RNA decreased the expression of beta2M after IFNgamma
      treatment. Our data point to the critical role of NFkappaB proteins in regulating
      the MHC-I expression in human pluripotent stem cells.

PMID- 22987394
TI  - Re-assigned diagnosis of D4ST1-deficient Ehlers-Danlos syndrome (adducted thumb
      clubfoot syndrome) after initial diagnosis of Marden-Walker syndrome.
AB  - We report on a 16-year-old female originally diagnosed with Marden-Walker
      syndrome due to features such as facial dysmorphism, several musculoskeletal
      anomalies, and atrial septal defect in addition to hypoplasia of the inferior
      vermis with normal-sized cerebellum and absence of the septum pellucidum.
      However, an SNP array performed at age 15 years detected a total of 142 Mb of
      long runs of homozygosity (ROH), and put the diagnosis in doubt. Using the
      Genomic Oligoarray and SNP array evaluation tool (http://www.ccs.miami.edu/ROH),
      CHST14 provided a "hit" as a gene mapping to the largest ROH region associated
      with a phenotype matching our patient's (if mutated). At that time, she was a
      cognitively intact, thin female with growth parameters below the 3rd percentile.
      Craniofacial features included microcephaly, midface hypoplasia,
      blepharophimosis, entropion, myopia, microretrognathia, and dental malocclusion.
      Musculoskeletal features included kyphoscoliosis, arachnodactyly, camptodactyly,
      and rocker-bottom feet with interphalangeal contractures. Her skin displayed
      large ecchymoses and poorly healed atrophic scars. Sequencing of CHST14 revealed
      a complex homozygous frameshift mutation involving a 7-bp deletion and an 11-bp
      insertion predicted to produce a truncated protein. This mutation was not seen in
      100 controls of various ethnicities. Thus, our patient represents not only a
      novel (homozygous) mutation in CHST14, but is also the first patient with
      dermatan 4-O-sulfotransferase 1-deficient Ehlers-Danlos syndrome (adducted thumb
      clubfoot syndrome) (DD-EDS ATCS) documented in the Western Hemisphere.
      Furthermore, our patient's central nervous system anomalies have not before been
      described in DD-EDS (ATCS).

PMID- 22987395
TI  - Synthesis of 3-oxaterpenoids and its application in the total synthesis of (+/-)
      moluccanic acid methyl ester.
AB  - Cascades: An InBr(3)-catalyzed intermolecular polyene cyclization initiated by a
      Prins reaction provides a concise approach to 3-oxaterpenoid derivatives. The
      reaction is compatible with various aldehydes, ketones, and polyolefin-alcohol
      substrates. In addition, the total synthesis of (+/-)-moluccanic acid methyl
      ester was achieved in seven steps by using such a Prins-polyene cyclization as
      the key step.

PMID- 22987397
TI  - DNA metalating-intercalating hybrid agents for the treatment of chemoresistant
      cancers.
AB  - Nonclassical platinum-based antitumor agents have shown enormous potential in the
      treatment of chemoresistant cancers. The design of these agents is based on the
      hypothesis that platinum-containing pharmacophores that react with nuclear DNA in
      cancer cells radically differently than the clinical agent cisplatin will produce
      a unique spectrum of biological activity. One such class of molecules are
      platinum-acridine hybrid agents derived from the prototypical complex
      [PtCl(en)(ACRAMTU)](NO(3))(2), en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9
      ylamino)ethyl]-1,3-dimethylthiourea ("PT-ACRAMTU"). This article summarizes
      milestones in the development of these agents and reviews critical key concepts
      that have guided their design and that of related compounds.

PMID- 22987396
TI  - Toll-like receptor 2 and palmitic acid cooperatively contribute to the
      development of nonalcoholic steatohepatitis through inflammasome activation in
      mice.
AB  - Innate immune signaling associated with Toll-like receptors (TLRs) is a key
      pathway involved in the progression of nonalcoholic steatohepatitis (NASH). Here
      we show that both TLR2 and palmitic acid are required for activation of the
      inflammasome, interleukin (IL)-1alpha, and IL-1beta, resulting in the progression
      of NASH. Wild-type (WT) and TLR2(-/-) mice were fed a choline-deficient amino
      acid-defined (CDAA) diet for 22 weeks to induce NASH. Bone marrow-transplanted
      TLR2 chimeric mice were generated after the recipient mice were lethally
      irradiated. Kupffer cells and hepatic stellate cells (HSCs) were isolated from WT
      mice and stimulated with TLR2 ligand and/or palmitic acid. WT mice on the CDAA
      diet developed profound steatohepatitis and liver fibrosis. In contrast, TLR2(-/
      ) mice had suppressed progression of NASH. Although both Kupffer cells and HSCs
      respond to TLR2 ligand, TLR2 bone marrow chimeric mice demonstrated that Kupffer
      cells were relatively more important than HSCs in TLR2-mediated progression of
      NASH. In vitro, palmitic acid alone did not increase TLR2 signaling-target genes,
      including cytokines and inflammasome components in Kupffer cells and HSCs. The
      TLR2 ligand increased Nod-like receptor protein 3, an inflammasome component, in
      Kupffer cells but not in HSCs. In the presence of TLR2 ligand, palmitic acid did
      induce caspase-1 activation and release of IL-1alpha and IL-1beta in Kupffer
      cells; however, these effects were not observed in HSCs. In vivo, WT mice on the
      CDAA diet showed increased caspase-1 activation in the liver and elevated serum
      levels of IL-1alpha and IL-1beta levels, which were suppressed in TLR2(-/-) mice.
      CONCLUSION: TLR2 and palmitic acid cooperatively activate the inflammasome in
      Kupffer cells and/or macrophages in the development of NASH.

PMID- 22987398
TI  - Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on
      human colon adenocarcinoma cells.
AB  - Recent studies report that chalcones exhibit cytotoxicity to human cancer cell
      lines. Typically, the form of cell death induced by these compounds is apoptosis.
      In the context of the discovery of new anticancer agents and in light of the
      antitumour potential of several chalcone derivatives, in the present study, we
      synthesized and tested the cytotoxicity of six chalcone derivatives on human
      colon adenocarcinoma cells. Six derivatives of 3-phenyl-1-(thiophen-2-yl) prop-2
      en-1-one were prepared and characterized on the basis of their (1) H and (13) C
      NMR spectra. HT-29 cells were treated with synthesized chalcones on two
      concentrations by three different incubation times. Cells were evaluated by cell
      morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry
      (annexin V) and gene expression analyses to determine the cytotoxic way.
      Chalcones 3-(4-bromophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C06) and 3-(2
      nitrophenyl)-1-(thiophen-2-yl)prop-2-en-1-one (C09) demonstrated higher
      cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT
      assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay.
      These data were confirmed by a decreased expression of anti-apoptotic genes and
      increased pro-apoptotic genes. Our findings indicate in summary that the
      cytotoxic activity of chalcone C06 on colorectal carcinoma cells occurs by
      apoptosis.

PMID- 22987399
TI  - White matter changes in primary dystonia determined by 2D distribution analysis
      of diffusion tensor images.
AB  - PURPOSE: To determine brain tissue affected by dystonia by making group
      comparison of parameter-based diffusion tensor imaging (DTI) distributions of
      patients with control subjects. A 2D distribution analysis of mean diffusivity
      and fractional anisotropy index was used for modeling brain tissues according to
      the inherent diffusion characteristics. MATERIALS AND METHODS: Seven affected
      carriers of the DYT1 dystonia mutation and eight healthy control subjects were
      imaged for a previous study. We employed a 2D distribution analysis of all the
      diffusion voxels and a four compartmental brain model for group comparison of the
      dystonia subjects and controls. RESULTS: Our analysis showed disease involvement
      in the white matter of the patients. Excellent tissue characterization was
      achieved automatically using the 2D distribution analysis based on a physical
      brain model. CONCLUSION: This 2D analysis implicated white matter in dystonia and
      could be useful as a screening tool in diseases with unknown pathologies.

PMID- 22987400
TI  - X-ray diffraction and infrared spectroscopy of N,N-dimethylformamide and dimethyl
      sulfoxide solvatomorphs of betulonic acid.
AB  - X-ray diffraction and infrared spectroscopy measurements for the N,N
      dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) solvatomorphs of betulonic
      acid (BA) were investigated. BA [3-oxolup-20(29)-en-28-oic acid, C(30)H(46)O(3)]
      exhibits a wide spectrum of biological activities and is considered to be a
      promising natural agent for the treatment of various cancer diseases. BA as a
      noncrystalline substance was obtained by oxidation of betulin. Crystal structures
      and the spectral data allowed analysis of hydrogen bonding (H-bonding), molecular
      conformation, and crystal packing differences in the solvatomorphs. Crystals of
      BA solvates were grown from the DMF-acetone (1:10, v/v) and DMSO-water (9:1, v/v)
      solutions. BA-DMF (1:1) solvate crystallizes in the monoclinic P2(1) space group,
      Z = 2. The unit cell parameters are as follows: cell lengths a = 13.2458(5) A, b
      = 6.6501(2) A, c = 17.9766(7) A, and beta = 110.513(4) degrees . BA-DMSO (1:1)
      solvate crystallizes in the orthorhombic P2(1)2(1)2(1) (Z = 4) space group with
      the following unit cell parameters: a = 6.6484(4) A, b = 13.3279(8) A, and c =
      32.6821(19) A. Conformational analysis of the six-membered rings, cyclopentane
      ring, and isopropenyl group showed differences in comparison with other betulin
      derivatives examined earlier. For both solvates, the intermolecular packing
      arrangement was governed mainly by H-bonds. The shortest H-bonds with D...A
      distances of 2.604 and 2.657 A, and almost linear DH...A connection occurred
      between OH of carboxylic group of BA and oxygen atoms from O=C and O=S groups of
      DMF and DMSO, respectively.

PMID- 22987401
TI  - The phytoplasmas: an introduction.
AB  - This volume of "Methods in Molecular Biology" entitled "Phytoplasmas: Methods and
      Protocols" aims to provide a broad range of protocols for working with this group
      of plant pathogens. In this first chapter, we provide some background information
      about the phytoplasmas to put the protocols into context.

PMID- 22987402
TI  - Techniques for the maintenance and propagation of phytoplasmas in glasshouse
      collections of Catharanthus roseus.
AB  - Phytoplasma collections are a vital resource for researchers and diagnosticians
      studying phytoplasma diseases. They provide material as a point of reference and
      a research tool to increase our understanding of phytoplasmas and the diseases
      they cause. This chapter describes the techniques required to create and maintain
      collections of phytoplasma-infected Catharanthus roseus (Madagascar periwinkle).

PMID- 22987403
TI  - Micropropagation and maintenance of phytoplasmas in tissue culture.
AB  - Maintenance of phytoplasma strains in tissue culture is achievable for all
      strains transmitted to periwinkle (Catharanthus roseus), and also for other
      naturally infected plant host species. Shoots of 1-3 cm length are grown in a
      solid medium containing Murashige and Skoog (MS) micro- and macroelements and
      0.12 mg/L benzylaminopurine. The continued presence of phytoplasmas in infected
      shoots of periwinkle that have been maintained in micropropagation for up to 20
      years can be shown by diagnostic methods such as nested PCR tests using the 16S
      rDNA gene (see Chapters 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,and 26 for
      phytoplasma diagnostic methods).

PMID- 22987404
TI  - Dodder transmission of phytoplasmas.
AB  - Transmission of phytoplasmas from naturally infected plant host species using the
      parasitic plant Cuscuta spp. (dodder) to Catharanthus roseus (Madagascar
      periwinkle) is an effective way to maintain a wide range of phytoplasmas for
      further research. Here, we describe transmission via dodder from an infected
      medicinal plant Rehmannia glutinosa var. purpurea and from a symptomatic
      redcurrant plant (Ribes spp.) to C. roseus indicator plants using a "stable
      bridges" method. In both cases, typical symptoms of phytoplasma disease on
      periwinkle plants were obtained: virescent flowers with an increased number of
      axillary shoots and smaller leaves after transmission from R. glutinosa, and
      greening petals (virescence) after transmission from Ribes spp. Phytoplasmas
      could be detected in donor and recipient plants by electron microscopy and by
      polymerase chain reaction (PCR) assays using universal phytoplasma primer pairs.
      Restriction fragment length polymorphism analyses of PCR fragments can also be
      used to confirm the identity of the phytoplasmas from donor and recipient plants.

PMID- 22987405
TI  - Insect maintenance and transmission.
AB  - Phytoplasmas are plant pathogens of huge economic importance due to
      responsibility for crop yield losses worldwide. Institutions around the world are
      trying to understand and control this yield loss at a time when food security is
      high on government agendas. In order to fully understand the mechanisms of
      phytoplasma infection and spread, more insect vector and phytoplasma colonies
      will need to be established for research worldwide. Rearing and study of these
      colonies is essential in the research and development of phytoplasma control
      measures. This chapter highlights general materials and methods for raising
      insect vector colonies and maintenance of phytoplasmas. Specific methods of
      rearing the maize leafhopper and maize bushy stunt phytoplasma and the aster
      leafhopper and aster yellows phytoplasma strain witches' broom are also included.

PMID- 22987406
TI  - Capturing insect vectors of phytoplasmas.
AB  - Insect vectors of phytoplasmas are limited to leafhoppers, planthoppers, and
      psyllids. While populations can be monitored by a number of passive techniques in
      the field, the capture of live insects is necessary for manipulation and study. A
      number of physical methods for capturing these insects already exist, but more
      innovative traps equipped with infochemical lures for species-specific monitoring
      and mass trapping are being developed.

PMID- 22987407
TI  - Insect vector transmission assays.
AB  - Phytoplasmas are transmitted in a persistent propagative manner by phloem-feeding
      vectors belonging to the order Hemiptera, suborder Homoptera. Following
      acquisition from the infected source plant, there is a latent period before the
      vector can transmit, so transmission assays consist of three basic steps:
      acquisition, latency, and inoculation. More than 90 vector species (plant-,
      leafhoppers, and psyllids) have been discovered so far but many others are still
      undiscovered, and their role in spreading economically important crop diseases is
      neglected. Therefore, screening for vectors is an essential step in developing
      rational control strategies targeted against the actual vectors for phytoplasma
      associated diseases. The mere detection of a phytoplasma in an insect does not
      imply that the insect is a vector; a transmission assay is required to provide
      conclusive evidence. Transmission experiments can be carried out using insects
      from phytoplasma-free laboratory colonies or field-collections. Moreover,
      transmission assays can be performed by feeding vectors on an artificial diet
      through Parafilm((r)), after which phytoplasmas can be detected in the sucrose
      feeding medium by PCR. Transmission trials involve the use of different
      techniques according to the biology of the different vector species;
      planthoppers, leafhoppers, and psyllids.

PMID- 22987408
TI  - Molecular identification of phytoplasma vector species.
AB  - The correct identification of the insect species involved in phytoplasma
      transmission is an essential condition for managing phytoplasma diseases and
      employing control strategies. The taxonomy of leafhoppers, planthoppers, and
      psyllids traditionally relies on morphological characters. Unfortunately, the
      identification of the distinctive traits requires skills and experience possessed
      by only a few specialist entomologists. In this chapter we provide protocols for
      the molecular identification of phytoplasma-vector species, mainly based on the
      polymerase chain reaction (PCR) amplification of mitochondrial and ribosomal DNA.
      Protocols for the application of molecular identification keys to dried specimens
      stored in insect collections are also provided. The same total DNA preparations
      can serve as a PCR template for either insect species or phytoplasma
      identification. The molecular identification methods can be applied not only to
      males, but also to nymphs and females for which a morphological taxonomic tool is
      generally unavailable. We suggest that taxonomic databases of planthoppers,
      leafhoppers, and psyllids should include species-specific DNA sequences as soon
      as they become available.

PMID- 22987409
TI  - Dienes' staining and light microscopy for phytoplasma visualization.
AB  - The chapter describes the main light microscopy techniques used for the diagnosis
      of phytoplasmas. Because the described techniques are generally only effective in
      cases where the concentration of the pathogen inside the host phloem tissue is
      high, they are useful as preliminary methods to assess the presence of
      phytoplasmas and analyze the distribution in symptomatic plants.

PMID- 22987410
TI  - DAPI staining and fluorescence microscopy techniques for phytoplasmas.
AB  - The 4',6-diamidino-2-phenylindole (DAPI) stain technique is a simple method that
      was developed for confirming the presence of phytoplasmas in hand-cut or freezing
      microtome sections of infected tissues. DAPI binds AT-rich DNA preferentially, so
      that phytoplasmas, localized among phloem cells, can be visualized in a
      fluorescence microscope. The procedure is quick, easy to use, inexpensive, and
      can be used as a preliminary or quantitative method to detect or quantify
      phytoplasma-like bodies in infected plants.

PMID- 22987411
TI  - Visualization of phytoplasmas using electron microscopy.
AB  - The use of electron microscopy, both transmission and scanning, provides reliable
      and accurate methods for detecting phytoplasmas in plants. Our understanding of
      these pathogens, their morphology, development, and intracellular location in
      plants and insect vectors has been greatly increased through the use of these
      instruments. Development of techniques such as immunolabeling, cryofixation with
      freeze substitution or plunge freezing with direct transfer to the microscope
      stage, together with advances in instrumentation is enabling us to study these
      pathogens under conditions close to their native state. The visualization of fine
      detail and ultrastructure, using modern and established techniques, can only be
      appreciated by the magnification and spatial resolution offered in the electron
      microscopes. Now that the full sequencing of four phytoplasma genomes (to date)
      has been achieved, electron microscopy can play an important role in identifying
      and understanding specific gene functions.

PMID- 22987413
TI  - DNA extraction from arborescent monocots and how to deal with other challenging
      hosts.
AB  - Detection of pathogen DNA by polymerase chain reaction (PCR) assays is the most
      widely used method for diagnosing phytoplasma diseases. Reliable and efficient
      detection of phytoplasmas, especially in woody perennial plants, is challenging
      due to the unusually low abundance and sporadic distribution of phytoplasmas
      within infected host tissues. Detection success depends largely upon the host
      species and sampling procedures and, to a lesser extent, on the protocol used for
      DNA extraction. Here we describe a simple, straightforward, nondestructive stem
      sampling protocol to confirm phytoplasma infection of palms and other arborescent
      monocots of large stature. The protocol requires minimal processing of excised
      tissues and yields phytoplasma DNA preparations in suitable quantity for reliable
      detection by nested PCR assays.

PMID- 22987412
TI  - Automated DNA extraction for large numbers of plant samples.
AB  - The method described here is a rapid, total DNA extraction procedure applicable
      to a large number of plant samples requiring pathogen detection. The procedure
      combines a simple and quick homogenization step of crude extracts with DNA
      extraction based upon the binding of DNA to magnetic beads. DNA is purified in an
      automated process in which the magnetic beads are transferred through a series of
      washing buffers. The eluted DNA is suitable for efficient amplification in PCR
      reactions.

PMID- 22987414
TI  - Nested PCR and RFLP analysis based on the 16S rRNA gene.
AB  - Current phytoplasma detection and identification methods are primarily based on
      nested polymerase chain reaction followed by restriction fragment length
      polymorphism analysis and gel electrophoresis. These methods can potentially
      detect and differentiate all phytoplasmas including those previously not
      described. The present protocol describes the application of this method for
      identification of phytoplasmas at 16S rRNA (16Sr) group and 16Sr subgroup levels.

PMID- 22987415
TI  - PCR and RFLP analyses based on the ribosomal protein operon.
AB  - Differentiation and classification of phytoplasmas have been primarily based on
      the highly conserved 16S rRNA gene. RFLP analysis of 16S rRNA gene sequences has
      identified 31 16S rRNA (16Sr) groups and more than 100 16Sr subgroups.
      Classification of phytoplasma strains can, however, become more refined and
      specific if moderately conserved genes, such as the ribosomal protein (rp) genes,
      are used as genetic markers. The use of additional genetic markers enhances the
      resolving power of phytoplasma classification. This chapter describes the
      methodology of detection, differentiation, and classification of phytoplasma
      strains based on rp gene sequences. RFLP analysis of amplicons obtained by group-
      or subgroup-specific rp gene-based primers is used for finer differentiation of
      phytoplasma strains within a given group or subgroup. The rp gene-based
      classification not only readily resolves 16Sr subgroups within a given 16Sr
      group, but also provides finer differentiation of closely related phytoplasma
      strains. Many individual 16Sr subgroups can be further differentiated into two or
      more distinct rp subgroups.

PMID- 22987416
TI  - Tuf and secY PCR amplification and genotyping of phytoplasmas.
AB  - Tuf and secY genotyping techniques have been developed to distinguish phytoplasma
      strains. Tuf polymerase chain reaction sequence analyses are available for
      phytoplasma taxonomic groups 16SrI, 16SrV, 16SrXII-A, and XII-B. In addition to
      their use to confirm the taxonomic status of phytoplasma strains, they allow the
      spread of phytoplasma strains in host plants and insect vectors to be traced.
      SecY is more variable than tuf and is therefore more discriminatory than tuf, but
      secY and tuf phylogenies show congruence.

PMID- 22987417
TI  - PCR analysis of phytoplasmas based on the secA gene.
AB  - Conventionally, diagnostics and phylogenetics of phytoplasmas have been primarily
      based on the 16S rRNA gene, for which "universal" primers are available that
      amplify from most phytoplasma 16Sr groups. However, there has been a drive in
      recent years to develop "universal" primers for other genes that can be used to
      complement the use of the 16S rRNA gene. This chapter details the use of primers
      based on the phytoplasma secA gene and describes how these primers can be used in
      both a single or nested PCR approach for amplification. It also notes the use of
      appropriate controls that should be undertaken and provides a source for
      phytoplasma secA sequences that are available in databases that can be used for
      phylogenetic analyses.

PMID- 22987418
TI  - Single-strand conformation polymorphism analysis for differentiating phytoplasma
      strains.
AB  - Single-strand conformation polymorphism (SSCP) analysis is a sensitive and rapid
      technique for detecting DNA polymorphisms and mutations in PCR-amplified
      fragments. Due to its technical simplicity, it is widely used as a screening tool
      in various investigations, ranging from clinical diagnosis of human hereditary
      diseases to the characterization of microbial communities. This method can also
      be used successfully on phytoplasmas as a tool for the detection of molecular
      variability in conserved housekeeping genes such as 16S rRNA and tuf, as well as
      in more variable genes, revealing the presence of polymorphisms undetected by
      routine RFLP analyses. The reliability of SSCP has been confirmed by multiple
      alignments and phylogenetic analyses of representative sequences showing
      different SSCP profiles. However, it is not broadly applied in phytoplasma
      research yet. The technique provides an inexpensive, convenient, and sensitive
      method for determining sequence variation and to differentiate phytoplasma
      strains, and is particularly suitable for epidemiological studies or as a fast
      screening, typing tool when dealing with a large number of field samples.

PMID- 22987419
TI  - Microarrays for universal detection and identification of phytoplasmas.
AB  - Detection and identification of phytoplasmas is a laborious process often
      involving nested PCR followed by restriction enzyme analysis and fine-resolution
      gel electrophoresis. To improve throughput, other methods are needed. Microarray
      technology offers a generic assay that can potentially detect and differentiate
      all types of phytoplasmas in one assay. The present protocol describes a
      microarray-based method for identification of phytoplasmas to 16Sr group level.

PMID- 22987420
TI  - T-RFLP for detection and identification of phytoplasmas in plants.
AB  - Conventionally, detection of phytoplasmas has been performed by PCR of the 16S
      rRNA gene, followed by either RFLP or DNA sequencing to determine the phytoplasma
      16Sr group. This chapter demonstrates the technique of terminal restriction
      fragment length polymorphism (T-RFLP), a fingerprinting technique which combines
      both detection and identification in a single method, with the added benefit of
      inbuilt controls which removes the risk of false negative results and in addition
      highlights potential false positive results.

PMID- 22987421
TI  - Real-time PCR for universal phytoplasma detection and quantification.
AB  - Currently, the most efficient detection and precise quantification of
      phytoplasmas is by real-time PCR. Compared to nested PCR, this method is less
      sensitive to contamination and is less work intensive. Therefore, a universal
      real-time PCR method will be valuable in screening programs and in other setups
      in which large numbers of samples are tested.

PMID- 22987422
TI  - A real-time PCR detection system for the bois noir and flavescence doree
      phytoplasmas and quantification of the target DNA.
AB  - The real-time PCR detection system for grapevine yellows phytoplasmas described
      here is composed of two assays for group-specific detection of flavescence doree
      (FD) and bois noir (BN) phytoplasmas and a universal phytoplasma assay. It uses
      hydrolysis minor groove binder probes (TaqMan-MGB). The addition of an assay for
      amplification of plant DNA co-extracted with phytoplasma DNA provides a further
      quality control for the DNA extraction and PCR amplification for each sample. The
      detection system described is reliable, specific, sensitive, and easily
      applicable to fast, high-throughput diagnosis of grapevine yellows phytoplasmas.
      In addition to the detection system, an approach for the quantification of
      phytoplasmas in the sample is described.

PMID- 22987423
TI  - Real-time PCR for specific detection of three phytoplasmas from the apple
      proliferation group.
AB  - In this chapter, we describe a real-time PCR detection system for fast, reliable,
      specific, and sensitive detection and discrimination of 'Candidatus Phytoplasma
      mali', 'Ca. P. prunorum', and 'Ca. P. pyri' from the 16SrX (apple proliferation
      AP) group. These phytoplasmas are causal agents of fruit tree diseases within the
      Rosaceae family, namely apple proliferation, European stone fruit yellows, and
      pear decline. The assays use (hydrolysis) TaqMan((r)) minor groove binder probes.
      The panel of assays comprises the same set of primers and specific probes for
      species-specific amplification, and an additional set of primers and probe for
      18S rRNA as an endogenous quality control of DNA extraction. The assays described
      can be used in routine phytoplasma surveys and in certification programmes.

PMID- 22987424
TI  - Reverse transcription-PCR for phytoplasma detection utilizing crude sap
      extractions.
AB  - Phytoplasmas are routinely detected by nucleic acid-based techniques. These
      approaches rely on enriched phytoplasma DNA extracts of good quality, following
      labor intensive and time-consuming purification protocols. Here we describe a
      very rapid, specific, sensitive, and reliable method for flavescence doree
      phytoplasma detection, based on real-time Taqman((r)) reverse transcription-PCR
      of the 16S rRNA. The protocol is particularly useful for large-scale screening of
      vineyards and nurseries, pathogen surveys, and field epidemiological studies.

PMID- 22987425
TI  - In-field diagnostics using loop-mediated isothermal amplification.
AB  - Loop-mediated isothermal amplification (LAMP) is a method for amplification and
      detection of target organisms which, unlike polymerase chain reaction, does not
      require thermal cycling. LAMP assays can be developed in the laboratory for
      subsequent deployment in the field, where the simplicity of isothermal
      amplification makes LAMP a suitable method for rapid detection of phytoplasmas
      with levels of sensitivity and specificity approaching those of more complex and
      time-consuming laboratory methods.

PMID- 22987426
TI  - DNA bar-coding for phytoplasma identification.
AB  - Phytoplasma identification has proved difficult due to their inability to be
      maintained in vitro. DNA barcoding is an identification method based on
      comparison of a short DNA sequence with known sequences from a database. A DNA
      barcoding tool has been developed for phytoplasma identification. While other
      sequence-based methods may be well adapted to identification of particular
      strains of phytoplasmas, often they cannot be used for the simultaneous
      identification of phytoplasmas from different groups. The phytoplasma DNA
      barcoding protocol in this chapter, based on the tuf and 16SrRNA genes, can be
      used to identify the following phytoplasma groups: 16SrI, 16SrII, 16SrIII,
      16SrIV, 16SrV, 16SrVI, 16SrVII, 16SrIX, 16SrX, 16SrXI, 16SrXII, 16SrXV, 16SrXX,
      16SrXXI.

PMID- 22987427
TI  - Phylogenetic analyses of phytoplasmas based on whole-genome comparison.
AB  - It is no longer as difficult to determine genomic DNA sequences of uncultured
      bacteria as it once was, due to the development of DNA sequencing technology. It
      is likely that the number of whole-genome sequences of phytoplasmas will
      increase. In this chapter, two major strategies of whole-genome comparison
      studies, viz. gene content and orthologous protein sequence comparisons, are
      described. In general, horizontal gene transfer has greater influence on gene
      content-based phylogenetic analysis than orthologous protein sequence-based
      analysis. However, horizontal gene transfer has occurred rarely during the
      evolution of Mollicutes. Thus, the two phylogenetic topologies of the Mollicutes
      based on the two different strategies are similar.

PMID- 22987428
TI  - The iPhyClassifier, an interactive online tool for phytoplasma classification and
      taxonomic assignment.
AB  - The iPhyClassifier is an internet-based research tool for quick identification
      and classification of diverse phytoplasmas. The iPhyClassifier simulates
      laboratory restriction enzyme digestions and subsequent gel electrophoresis and
      generates virtual restriction fragment length polymorphism (RFLP) patterns. Based
      on RFLP pattern similarity coefficient scores, the iPhyClassifier gives instant
      suggestions on group and subgroup classification status of the phytoplasma
      strains under study. The iPhyClassifier also aligns the query sequences with that
      of reference strains of all previously described 'Candidatus Phytoplasma'
      species, -calculates sequence similarity scores, and assigns the phytoplasmas
      under study into respective 'Ca. Phytoplasma' species as related strains
      according to the guidelines set forth by the Phytoplasma Taxonomy Group of the
      International Research Program on Comparative Mycoplasmology. Additional
      functions of the iPhyClassifier include delineation of potentially new
      phytoplasma groups and subgroups as well as new 'Ca. Phytoplasma' species. This
      chapter describes the program components, the operational procedure, and the
      underlying principles of the iPhyClassifier operation. The chapter also provides
      hints on how to interpret the results.

PMID- 22987429
TI  - Phytoplasma proteomic analysis.
AB  - Proteome analysis is becoming a powerful tool in the functional characterization
      of organisms, and takes a broad, comprehensive, systematic approach to
      understanding biology. Following the sequencing of the phytoplasma genomes, the
      next step is to characterize the expressed proteome of phytoplasmas to acquire
      the verification and functional annotation of all predicted genes and their
      protein products. Here, we describe the protocol of mulberry dwarf phytoplasma
      purification, phytoplasma protein extraction and separation by SDS-PAGE, in-gel
      tryptic digestion of the proteins, separation of the digested peptides by liquid
      chromatography, and identification of the peptides by mass spectrometry. The
      protocol described here is also applicable to the analysis of other phytoplasma
      proteomes.

PMID- 22987430
TI  - Preparation of phytoplasma membrane recombinant proteins.
AB  - The study of phytoplasma membrane protein interactions with host cell proteins is
      crucial to understand the life cycle of these unculturable microorganisms within
      their hosts. A step-by-step protocol for the heterologous expression of
      phytoplasma membrane proteins in Escherichia coli is described, together with a
      procedure to purify a suitable quantity of fusion antigen for application in the
      study of phytoplasma-host interactions.

PMID- 22987431
TI  - Phytoplasma plasmid DNA extraction.
AB  - Phytoplasma plasmids have generally been detected from DNA extracted from plants
      and insects using methods designed for the purification of total phytoplasma DNA.
      Methods include extraction from tissues that are high in phytoplasma titre, such
      as the phloem of plants, with the use of CsCl-bisbenzimide gradients that exploit
      the low G+C content of phytoplasma DNA. Many of the methods employed for
      phytoplasma purification have been described elsewhere in this book. Here we
      describe in detail two methods that are specifically aimed at isolating plasmid
      DNA.

PMID- 22987432
TI  - Cesium chloride-bisbenzimide gradients for separation of phytoplasma and plant
      DNA.
AB  - CsCl-bisbezimide gradient centrifugation is a method to separate phytoplasma from
      host plant DNA. Bisbenzimide forms a complex with A + T-rich DNA thereby lowering
      its relative density. During centrifugation the A + T-rich phytoplasma DNA is
      spatially separated from the less A + T-rich host plant DNA. The difference in
      buoyant density between phytoplasma DNA and plant DNA varies according to the
      host-pathogen combination. The phytoplasma DNA forms a distinct band above the
      host plant DNA and can be collected. Depending on the phytoplasma titer and the
      scale of extraction, highly purified DNA is obtained in sufficient quantities for
      the construction of a genomic library, a sequencing project or hybridization
      studies.

PMID- 22987433
TI  - Pulsed-field gel electrophoresis for isolation of full-length phytoplasma
      chromosomes from plants.
AB  - Pulsed-field gel electrophoresis (PFGE) is a powerful technique for genomic
      studies of unculturable plant-pathogenic phytoplasmas, which enables separation
      of full-length phytoplasma chromosomes from contaminating host plant nucleic
      acids. The PFGE method described here involves isolation of phytoplasmal DNA from
      high-titer phytoplasma-infected herbaceous plants using a phytoplasma enrichment
      procedure, embedding of phytoplasma chromosomes in agarose blocks, and separation
      of entire phytoplasma chromosomes from contaminating host plant nucleic acids by
      electrophoresis. Full-length phytoplasma chromosomes are resolved as single,
      discrete bands in the gel. The identity of these bands can be confirmed by
      Southern blot hybridization using a ribosomal DNA fragment as a probe. The method
      does not utilize gamma-irradiation to linearize phytoplasma chromosomes prior to
      electrophoresis.

PMID- 22987434
TI  - Mapping the phytoplasma chromosome.
AB  - Physical and genetic mapping of the phytoplasma chromosome can be a useful tool
      in a genome sequencing project in order to assemble the in silico-predicted
      contigs robustly. Mapping consists of four distinct steps: preparation of
      phytoplasma chromosomes from infected plants, single- and double-digestion of
      chromosomes with rare-cutting restriction enzymes, separation of large DNA
      fragments by pulsed-field gel electrophoresis, and hybridization with various
      genetic markers. Materials and methods needed for each step are described and the
      technique is illustrated using the flavescence doree phytoplasma genome map as an
      example.

PMID- 22987435
TI  - Multimodal nonlinear microscopic investigations on head and neck squamous cell
      carcinoma: toward intraoperative imaging.
AB  - BACKGROUND: Prognosis and appropriate treatment of head and neck squamous cell
      carcinoma (HNSCC) depend on the tumor type routinely derived by invasive
      histopathology. A promising noninvasive alternative is nonlinear optical imaging,
      which is capable of in vivo tissue visualization for tumor typing and grading.
      METHODS AND RESULTS: Thin tissue sections from 3 patients aged 56 to 60 years
      presenting advanced carcinoma of the hypopharynx, larynx, and left tonsil were
      investigated by coherent anti-Stokes Raman scattering (CARS), second-harmonic
      generation (SHG), and 2 photon excited fluorescence (TPEF) to study the
      morphochemistry of the tissues. Morphologic alterations of prognostic
      significance, such as cell density, nuclear to cytoplasm ratio, and
      keratinization as well as the underlying compositional changes during malignant
      transformation were determined, such as the distributions of lipids, collagen,
      and autofluorophors. CONCLUSIONS: Nonlinear imaging provides a noninvasive
      optical biopsy of the epithelial layer comparable to staining microscopy. By
      integration into an operational microscope, routine screening of suspicious
      lesions and surgical guidance can be realized.

PMID- 22987436
TI  - Abstracts of the 44th Congress of the International Society of Paediatric
      Oncology (SIOP) 2012, October 5-8, 2012, London, United Kingdom.

PMID- 22987437
TI  - Mortality audit of the Finnish cervical cancer screening program.
AB  - Incidence-based evaluations of cervical cancer screening programs have suggested
      age-specific impacts and there is uncertainty regarding the effectiveness of
      screening outside the ages of 30-60 years. We audited the screening histories of
      cervical cancer deaths and conducted a case-control evaluation of the
      effectiveness of organized screening in different ages with mortality as outcome.
      We included all 506 cervical cancer deaths in Finland in 2000-2009 due to cancers
      diagnosed in 1990 or later, and 3,036 controls matched by age at diagnosis to the
      cases. Squamous cell carcinoma constituted 59% of the cases, adenocarcinomas 29%,
      and the remaining 12% were other specified and unspecified cervical malignancies.
      Most deaths (54%) were due to cancers diagnosed more than 5 years after last
      screening invitation, 24% were diagnosed among nonattenders and only 14% of
      deaths occurred among women who had attended invitational screening. The risk
      reduction associated with attending a single program screen at an age below 40
      was nonsignificant (OR 0.70; 95% CI 0.33-1.48), while clear risk reductions were
      observed after screening at the age of 40-54 (OR 0.33; CI 0.20-0.56) and 55-69
      (OR 0.29; CI 0.16-0.54). This study also provides some indication of a long
      lasting additional effect of screening at the age of 65. Possible avenues for
      improving the effectiveness of the Finnish screening program include efforts to
      increase attendance and an extension of the target ages to include 65-to 69-year
      old women. The potential benefit of increasing the sensitivity of the screening
      test or shortening the screening interval is smaller.

PMID- 22987439
TI  - Synthesis and applications of graphene-based TiO(2) photocatalysts.
AB  - Graphene is one of the most promising materials in the field of nanotechnology
      and has attracted a tremendous amount of research interest in recent years. Due
      to its large specific surface area, high thermal conductivity, and superior
      electron mobility, graphene is regarded as an extremely attractive component for
      the preparation of composite materials. At the same time, the use of
      photocatalysts, particularly TiO(2), has also been widely studied for their
      potential in addressing various energy and environmental-related issues. However,
      bare TiO(2) suffers from low efficiency and a narrow light-response range.
      Therefore, the combination of graphene and TiO(2) is currently one of the most
      active interdisciplinary research areas and demonstrations of photocatalytic
      enhancement are abundant. This Review presents and discusses the current
      development of graphene-based TiO(2) photocatalysts. The theoretical framework of
      the composite, the synthetic strategies for the preparation and modification of
      graphene-based TiO(2) photocatalysts, and applications of the composite are
      reviewed, with particular attention on the photodegradation of pollutants and
      photocatalytic water splitting for hydrogen generation.

PMID- 22987440
TI  - Prominent electronic and geometric modifications of palladium nanoparticles by
      polymer stabilizers for hydrogen production under ambient conditions.
AB  - A remarkable effect from the modification of electronic and geometric properties
      of Pd nanoparticles by the use of polymer pendant groups bound to the surface of
      palladium nanoparticles is reported. The degree of electron promotion to the Pd
      nanoparticles under ambient conditions was found to be dependent on the
      availability of the lone pair electrons of the pendant groups.

PMID- 22987438
TI  - Molecular scaffolds underpinning macroglial polarization: an analysis of retinal
      Muller cells and brain astrocytes in mouse.
AB  - Key roles of macroglia are inextricably coupled to specialized membrane domains.
      The perivascular endfoot membrane has drawn particular attention, as this domain
      contains a unique complement of aquaporin-4 (AQP4) and other channel proteins
      that distinguishes it from perisynaptic membranes. Recent studies indicate that
      the polarization of macroglia is lost in a number of diseases, including temporal
      lobe epilepsy and Alzheimer's disease. A better understanding is required of the
      molecular underpinning of astroglial polarization, particularly when it comes to
      the significance of the dystrophin associated protein complex (DAPC). Here, we
      employ immunofluorescence and immunogold cytochemistry to analyze the molecular
      scaffolding in perivascular endfeet in macroglia of retina and three regions of
      brain (cortex, dentate gyrus, and cerebellum), using AQP4 as a marker. Compared
      with brain astrocytes, Muller cells (a class of retinal macroglia) exhibit lower
      densities of the scaffold proteins dystrophin and alpha-syntrophin (a DAPC
      protein), but higher levels of AQP4. In agreement, depletion of dystrophin or
      alpha-syntrophin--while causing a dramatic loss of AQP4 from endfoot membranes of
      brain astrocytes--had only modest or insignificant effect, respectively, on the
      AQP4 pool in endfoot membranes of Muller cells. In addition, while polarization
      of brain macroglia was less affected by dystrophin depletion than by targeted
      deletion of alpha-syntrophin, the reverse was true for retinal macroglia. These
      data indicate that the molecular scaffolding in perivascular endfeet is more
      complex than previously assumed and that macroglia are heterogeneous with respect
      to the mechanisms that dictate their polarization.

PMID- 22987442
TI  - Hand preference for tool-use in capuchin monkeys (Cebus apella) is associated
      with asymmetry of the primary motor cortex.
AB  - Skilled motor actions are associated with handedness and neuroanatomical
      specializations in humans. Recent reports have documented similar neuroanatomical
      asymmetries and their relationship to hand preference in some nonhuman primate
      species, including chimpanzees and capuchin monkeys. We investigated whether
      capuchins displayed significant hand preferences for a tool-use task and whether
      such preferences were associated with motor-processing regions of the brain.
      Handedness data on a dipping tool-use task and high-resolution 3T MRI scans were
      collected from 15 monkeys. Capuchins displayed a significant group-level left
      hand preference for this type of tool use, and handedness was associated with
      asymmetry of the primary motor cortex. Left-hand preferent individuals displayed
      a deeper central sulcus in the right hemisphere. Our results suggest that
      capuchins show an underlying right-hemisphere bias for skilled movement.

PMID- 22987443
TI  - Symmetric expansion of neural stem cells from the adult olfactory bulb is driven
      by astrocytes via WNT7A.
AB  - Adult neural stem cells (NSCs) located in the subventricular zone (SVZ)
      persistently produce new neurons destined to the olfactory bulb (OB). Recent
      research suggests that the OB is also a source of NSCs that remains largely
      unexplored. Using single/dual-labeling procedures, we address the existence of
      NSCs in the innermost layers of the OB. In vivo, these cells are more quiescent
      that their SVZ counterparts, but after in vitro expansion, they behave similarly.
      Self-renewal and proliferation assays in co-culture with niche astrocytes
      indicate that OB-glia restricts NSC activity whereas SVZ-glia has the opposite
      effect. Gene expression profiling identifies WNT7A as a key SVZ-glial factor
      lacking in OB-glia that enhances self-renewal, thereby improving the propagation
      of OB-NSC cultures. These data demonstrate that region-specific glial factors
      account for in vivo differences in NSC activity and point to WNT7A as a tool that
      may be instrumental for the NSC expansion phase that precedes grafting.

PMID- 22987445
TI  - Comparison among direct, indirect and index selections on agronomic traits and
      nutritional quality traits in common bean.
AB  - BACKGROUND: Selection indices are linear combinations that allow the selection of
      several characters simultaneously. The objective of this study was to verify the
      efficiency of direct selection, indirect selection and selection indices in the
      identification of higher inbred common bean lines for grain yield, morphological,
      phenological and nutritional traits. RESULTS: There is genetic variability for
      grain yield, lodging, general adaptation note, cycle, insertion of the first pod,
      calcium and iron concentrations in the seeds. Moderate phenotypic correlation
      coefficients were observed between grain yield and general adaptation note (r = 
      0.57) and cycle (r = -0.57). When direct selection was performed for grain yield,
      the insertion of the first pod, calcium and iron concentrations showed negative
      indirect selection gains. The classic index showed that the distribution of gains
      has become more balanced: grain yield (39.05%), calcium (8.29%) and iron
      concentration (1.64%). CONCLUSION: Direct selection and indirect selection are
      not efficient in the simultaneous selection of agronomic traits and nutritional
      quality in common bean. The classical, base and multiplicative indexes provide
      responses of gain balanced among traits and superior genetic progress in the
      selection of inbred common bean lines, and have a high coincidence between the
      lines selected.

PMID- 22987446
TI  - Novel bisthienylethene containing ferrocenyl-substituted naphthalimide: a photo-
      and redox multi-addressable molecular switch.
AB  - A new photochromic bisthienylethene system (BTE-NAFc) is reported in which the
      ferrocene unit (Fc) is incorporated into a naphthalimide chromophore as the
      central ethene bridging unit. The incorporated Fc unit in the photochromic system
      of BTE-NAFc has several effects on optical properties, such as fluorescence
      modulation through photoinduced electron transfer (PET), a decrease in the
      photochromic cyclization quantum yield, and a selective two-step oxidation
      process. The ability to drive ring-opening and ring-closing reactions with a
      secondary redox-modulation provides increased functionality to the photochromic
      system. Based on these meaningful photo- and redox-modulation properties, five
      unprecedented multi-addressable states (BTE-NAFc, BTE-NAFc(+), c-BTE-NAFc, c-BTE
      NAFc(+), and BTE(+)-NAFc(+)) and gated photochromism are successfully obtained
      within the unimolecular BTE platform, thus providing deeper insight into
      photochromic systems as multifunctional outputs.

PMID- 22987448
TI  - Cancer-related risk factors and preventive measures in US Hispanics/Latinos.
AB  - In this article, we provide prevalence data on major cancer-related risk factors,
      early detection testing, and vaccination among Hispanics using nationally
      representative surveys. Compared with non-Hispanic whites, Hispanic adults are
      less likely to be current smokers (13% vs 22%) or frequent alcohol drinkers, but
      they are more likely to be obese (32% vs 26%) and to have lower levels of
      mammography use within the past year (46% vs 51%), colorectal screening as per
      recommended intervals (47% vs 61%), and Papanicolaou (Pap) test use within the
      past 3 years (74% vs 79%). Within the Hispanic population, the prevalence of
      these risk factors and early detection methods substantially vary by country of
      origin. For example, Cuban men (20.7%) and Puerto Rican men (19%) had the highest
      levels of current smoking than any other Hispanic subgroups, while Mexican women
      had the lowest levels of mammogram use (44%) and Pap test use (71%). Hispanic
      migrants have a higher prevalence of hepatitis B virus and Helicobacter pylori,
      which cause liver and stomach cancer, respectively. Among Hispanic adolescents,
      tobacco use (eg, 20.8% use of any tobacco products), alcohol use (42.9%), and
      obesity (23.2%) remain highly prevalent risk factors. Although 56% of Hispanic
      adolescents initiate human papillomavirus vaccination, only 56% of them completed
      the 3-dose series. Differences in risk factors and early detection testing among
      Hispanic groups should be considered in clinical settings and for cancer control
      planning.

PMID- 22987449
TI  - Janus kinase 2 and signal transducer and activator of transcription 3 activation
      is not essential for CCL3-, CCL5- or CCL8-induced chemotaxis.
AB  - Chemokine receptors induce cell migration, but the molecular basis of the signal
      cascade involved is not completely understood. Therefore, we investigated here
      the molecular mechanisms of CCL3-, CCL5- and CCL8-induced cells migration and
      investigated whether the Janus kinase/signal transducer and activator of
      transcription (STAT) signalling pathway is involved. Some STAT3 inhibitors, like
      Cucurbitacin I, destroy the actin cytoskeleton inside the cells and therefore
      prevent any cellular migration. However, for inhibitors that do not affect the
      actin cytoskeleton or induce cell death, we show that chemokine-induced cell
      migration is not dependent on activation of Janus kinase 2 or STAT3.

PMID- 22987447
TI  - New genetic findings in parotid gland pleomorphic adenomas.
AB  - BACKGROUND: Despite numerous studies, the tumor biology of pleomorphic adenomas,
      the most common salivary gland tumors, is still not completely defined. In order
      to identify further candidate genes important for tumor biology of pleomorphic
      adenomas, extended cytogenetic and molecular analysis are mandatory. METHODS: We
      performed a detailed molecular cytogenetic analysis using comparative genomic
      hybridization (CGH) followed by fluorescence in situ hybridization (FISH) with
      probes for chromosome X, 16p, 17, and 20 on a large cohort of pleomorphic
      adenomas (n = 29). RESULTS: We could confirm previously described deletions in
      pleomorphic adenomas affecting 16p, 17, 20q, and 22 by FISH and/or CGH analysis.
      Moreover, our CGH study revealed novel candidate regions on 8p23.1pter, 9p,
      10q25.1q25.3, and 11q24qter in the series of analyzed pleomorphic adenomas.
      CONCLUSION: Our present study reveals new insights in novel candidate regions
      implicated in pleomorphic adenoma tumorigenesis which should be considered in
      further molecular studies.

PMID- 22987450
TI  - SOT/EUROTOX debate: biomarkers from blood and urine will replace traditional
      histopathological evaluation to determine adverse responses.
AB  - The 2011 SOT/EUROTOX debate addressed the proposition that "Biomarkers From Blood
      and Urine will Replace Traditional Histopathological Evaluation to Determine
      Adverse Responses," identifying and comparing the strengths and limitations of
      histopathology and serum and urine biomarkers. Histopathology has a long and
      successful history in toxicity testing and a well-defined experience with the
      technique. Advantages include simplicity and general utility, sensitivity,
      spatial, and temporal resolution, a recognized role in defining adversity, the
      ability to use archived samples as a resource, and the ability to adapt to the
      advent of new molecular pathology tools and endpoints. On the other hand, safety
      biomarkers can be used to predict, detect, and monitor drug-induced toxicity
      during both preclinical studies and human trials. Unlike techniques for
      histopathology, blood and urine biomarkers are noninvasive but remain
      quantifiable and of translational value. Biomarker measurements reflect the time
      course of an injury and provide information on the molecular mechanisms of
      toxicity. After presenting the assenting and dissenting positions on the
      proposition, this article discusses the uses and the limitations of having a gold
      standard, how adverse responses are determined, the evolutionary (as opposed to
      revolutionary) process by which one technology is typically replaced by another,
      and the overall goal of developing biomarkers which can translate from
      preclinical safety assessment to clinical utility. The ultimate purpose of this
      discussion is to help researchers and regulators understand the challenges they
      face in the development and integration of new and existing biomarkers to
      determine adverse responses.

PMID- 22987451
TI  - Prediction of liver injury induced by chemicals in human with a multiparametric
      assay on isolated mouse liver mitochondria.
AB  - Drug-induced liver injury (DILI) in humans is difficult to predict using
      classical in vitro cytotoxicity screening and regulatory animal studies. This
      explains why numerous compounds are stopped during clinical trials or withdrawn
      from the market due to hepatotoxicity. Thus, it is important to improve early
      prediction of DILI in human. In this study, we hypothesized that this goal could
      be achieved by investigating drug-induced mitochondrial dysfunction as this toxic
      effect is a major mechanism of DILI. To this end, we developed a high-throughput
      screening platform using isolated mouse liver mitochondria. Our broad spectrum
      multiparametric assay was designed to detect the global mitochondrial membrane
      permeabilization (swelling), inner membrane permeabilization (transmembrane
      potential), outer membrane permeabilization (cytochrome c release), and
      alteration of mitochondrial respiration driven by succinate or malate/glutamate.
      A pool of 124 chemicals (mainly drugs) was selected, including 87 with documented
      DILI and 37 without reported clinical hepatotoxicity. Our screening assay
      revealed an excellent sensitivity for clinical outcome of DILI (94 or 92%
      depending on cutoff) and a high positive predictive value (89 or 82%). A highly
      significant relationship between drug-induced mitochondrial toxicity and DILI
      occurrence in patients was calculated (p < 0.001). Moreover, this multiparametric
      assay allowed identifying several compounds for which mitochondrial toxicity had
      never been described before and even helped to clarify mechanisms with some drugs
      already known to be mitochondriotoxic. Investigation of drug-induced loss of
      mitochondrial integrity and function with this multiparametric assay should be
      considered for integration into basic screening processes at early stage to
      select drug candidates with lower risk of DILI in human. This assay is also a
      valuable tool for assessing the mitochondrial toxicity profile and investigating
      the mechanism of action of new compounds and marketed compounds.

PMID- 22987456
TI  - Under-representation of minority ethnic groups in cardiovascular research: a semi
      structured interview study.
AB  - BACKGROUND: Minority ethnic groups are often excluded from research, and the
      reasons for this are complex. OBJECTIVE: This study aimed to explore why minority
      ethnic groups do not participate in research, and how their participation can be
      increased. METHODS: Ninety-one interviews were undertaken with people who either
      had (n = 48) or had not (n = 43) responded to the invitation to take part in a
      community heart failure screening study. These were split across four ethnic
      groups (African Caribbean, Bangladeshi, Indian and Pakistani) and between men and
      women. Participants were interviewed once, face-to-face, either in English or
      with an interpreter if they wished. Interview transcripts were analysed
      thematically. RESULTS: The main reason for participating in the screening study
      was for a health/heart check. Many participants either had not understood that it
      was research or had not known what this meant. Most people who did not
      participate had not remembered receiving the invitation or had been unavailable
      at the time. Few participants, including those who had and those who had not
      participated in the screening study, had any understanding of the objectives and
      nature of research. Once this had been briefly explained to them, many described
      altruistic reasons for why they would participate in research in the future.
      CONCLUSIONS: We have shown that South Asians and Black African-Caribbean
      communities are willing to take part in research as long as they are approached
      directly and the reasons for the research and potential benefits are explained
      clearly to them.

PMID- 22987457
TI  - How reliable are stroke patients' reports of their numbers of general practice
      consultations over 12 months?
AB  - BACKGROUND: Data on primary health care use are frequently used in economic
      evaluations. However, it is unclear how patient self-reports of their number of
      consultations with their general practitioner (GP) relate to actual consultations
      in the electronic records. These data are crucial if self-reports are used to
      conduct economic evaluations. OBJECTIVES: To report the accuracy of stroke
      patients' self-reports of their number of primary care consultations over a 12
      month period by comparison with practice-held electronic records. We also
      recorded the number of contacts required to collect service use data from the
      practices. METHODS: We contacted 65 practices requesting electronic consultation
      records over 12 months for 115 stroke patients who took part in a trial of home
      blood pressure monitoring. Consultation rates from the electronic records were
      compared with patients' self-reported number of consultations from a
      questionnaire covering the same period. RESULTS: Fifty-one practices (78%)
      responded. Patients' questionnaires (n = 83) reported a mean of 5.7 consultations
      with their GP per year compared with 7.2 in the electronic records (difference
      1.6, 95% confidence interval 0.5-2.7, P < 0.01). The mean time taken to obtain
      records from practices was 6 weeks. CONCLUSIONS: Patients modestly under-reported
      the number of consultations they had with a GP. Obtaining patient records from
      practices required more effort than obtaining information from patient
      questionnaires at the same time as assessing main trial outcomes. If patient self
      reports of health care usage are used in economic evaluations in primary care,
      researchers should consider validating a sample against electronic records.

PMID- 22987455
TI  - Neuromyelitis optica IgG does not alter aquaporin-4 water permeability, plasma
      membrane M1/M23 isoform content, or supramolecular assembly.
AB  - Neuromyelitis optica (NMO) is thought to be caused by immunoglobulin G
      autoantibodies (NMO-IgG) against astrocyte water channel aquaporin-4 (AQP4). A
      recent study (Hinson et al. (2012) Proc Natl Acad Sci USA 109:1245-1250) reported
      that NMO-IgG inhibits AQP4 water permeability directly and causes rapid cellular
      internalization of the M1 but not M23 isoform of AQP4, resulting in AQP4
      clustering, enhanced complement-dependent cytotoxicity, and tissue swelling.
      Here, we report evidence challenging this proposed mechanism of NMO-IgG-mediated
      pathology. We measured osmotic water permeability by stopped-flow light
      scattering on plasma membrane vesicles isolated from AQP4-expressing CHO cells,
      an approach that can detect changes in water permeability as small as 5% and is
      not confounded by internalization effects. We found similar single-molecule water
      permeability for M1-AQP4 tetramers and M23-AQP4 clusters (orthogonal arrays of
      particles, OAPs). Exposure of AQP4 to high concentrations of NMO-IgG from six
      seropositive NMO patients, and to high-affinity recombinant monoclonal NMO
      antibodies, did not reduce AQP4 water permeability. Also, NMO-IgG did not reduce
      water permeability in AQP4-reconstituted proteoliposomes. In transfected cells
      expressing M1- or M23-AQP4 individually, NMO-IgG caused more rapid
      internalization of M23- than M1-AQP4. In cells coexpressing both isoforms, M1-
      and M23-AQP4 comingled in OAPs that were internalized together in response to NMO
      IgG. Super-resolution imaging and native gel electrophoresis showed that the size
      of AQP4 OAPs was not altered by NMO sera or recombinant NMO antibodies. We
      conclude that NMO-IgG does not: (i) inhibit AQP4 water permeability, (ii) cause
      preferential internalization of M1-AQP4, or (iii) cause intramembrane AQP4
      clustering.

PMID- 22987458
TI  - Hyperbaric oxygen in the treatment of childhood autism: a randomised controlled
      trial.
AB  - BACKGROUND: Promising results with hyperbaric therapy for children with autism
      have been reported, but most involved the use of only mild pressure with oxygen
      supplementation. To date, there has been no randomised, blinded trial of 100%
      oxygen administered at hyperbaric pressure. This study evaluated the efficacy of
      hyperbaric oxygen therapy (HBOT). METHODS: Sixty Thai children with autism, aged
      three to nine years, were randomly assigned to receive 20 one-hour sessions of
      either HBOT at 153 kPa (1.5 ATA) or sham air at 116 kPa (1.15 ATA). Effects on
      behaviour were measured using the Autism Treatment Evaluation Checklist score
      (ATEC) and clinical improvement was measured with the Clinical Global Impression
      (CGI) system; in particular the clinical change (CGIC) and severity (CGIS) sub
      scores. These were evaluated by parents and clinicians, both of whom were blinded
      to the actual exposure. RESULTS: The mean total ATEC scores by both parents and
      clinicians were significantly improved after intervention in both arms of the
      study compared to the score before intervention (P < 0.001 in both groups by
      parents, P = 0.015 in HBOT group and P = 0.004 in sham group by clinician). There
      were no statistically significant differences in average percentage changes of
      total ATEC score and all subscales scores when comparing the HBOT and sham air
      groups, either by parents or clinicians. Changes in the CGI scores following
      intervention were inconsistent between parents and clinicians. For severity
      scores (CGIS), parents rated their children as more improved following HBOT (P =
      0.005), while the clinicians found no significant differences (P = 0.10). On the
      other hand, for change scores (CGIC) the clinicians indicated greater improvement
      following HBOT (P = 0.03), but the parents found no such difference (P = 0.28).
      CONCLUSIONS: Children with autism who received 20 sessions of either HBOT or a
      sham air exposure had significant improvements in overall behaviour but there
      were no significant differences in improvement between groups. The inconsistent
      changes on CGI sub-scores between parents and clinicians are difficult to
      interpret, but no overall clinically significant benefit from HBOT could be
      shown. Both interventions were safe and well tolerated with minimal side effect
      from middle ear barotraumas.

PMID- 22987459
TI  - Monitoring carbon dioxide in mechanically ventilated patients during hyperbaric
      treatment.
AB  - BACKGROUND: Measurement of the arterial carbon dioxide (P(a)CO(2)) is an
      established part of the monitoring of mechanically ventilated patients. Other
      ways to get information about carbon dioxide in the patient are measurement of
      end-tidal carbon dioxide (P(ET)CO(2)) and transcutaneous carbon dioxide (PTCCO2).
      Carbon dioxide in the blood and cerebral tissue has great influence on
      vasoactivity and thereby blood volume of the brain. We have found no studies on
      the correlation between P(ET)CO(2) or P(TC)CO(2), and P(a)CO(2) during hyperbaric
      oxygen therapy (HBOT). METHOD: We studied 10 intubated and ventilatory stable
      patients during HBOT. End-tidal and transcutaneous measurements provided
      continuous data. Arterial blood samples were collected after reaching the
      operational pressure of 284 kPa (2.8 ATA) and analysed outside the chamber. A
      total of 17 paired samples of P(ET)CO(2), P(TC)CO(2) and P(a)CO(2) were obtained.
      RESULTS: There was a good correlation between P(ET)CO(2) and P(a)CO(2) using
      linear regression (r(2) = 0.83). Bland-Altman analysis showed that P(ET)CO(2) on
      average was 2.22 kPa higher than P(a)CO(2) with limits of agreement (LoA) at +/-
      2.4 kPa. P(TC)CO(2), on average, was 2.16 kPa lower than P(a)CO(2) and the
      correlation using linear regression was poor (r(2) = 0.24). Bland-Altman analysis
      revealed LoA at +/- 3.2 kPa. CONCLUSION: During hyperbaric conditions we found
      that P(ET)CO(2) as opposed to P(TC)CO(2) offered the greater precision, but there
      was great variability among patients. Care must be taken when using P(ET)CO(2) or
      P(TC)CO(2) as an estimate of P(a)CO(2).

PMID- 22987460
TI  - A review of 17 years of telephone calls to the Australian Diver Emergency Service
      (DES).
AB  - INTRODUCTION: The Diver Emergency Service (DES) in Australia provides specialised
      medical advice on diving incidents 24 hours a day to divers, dive operators,
      families and health professionals. It is operated from the Hyperbaric Medicine
      Unit of the Royal Adelaide Hospital where the physician-on-call also carries the
      DES phone (1800-088200 or +61-8-8212-9242). METHODS: Data from calls to the
      service have been compiled into a computer database since 1991. Calls for the 17
      years from 1991 through 2007 were analysed. RESULTS: A total of 6,083 calls were
      logged, an average of 358 calls a year. Calls from Queensland and New South Wales
      each accounted for 25% of calls. Calls originating from outside Australia have
      been increasing and now make up 25% of calls. The diver themselves initiated the
      call 50% of the time and 66% of the calls were about male divers. The age range
      of divers was 12 to 95 years old. The mean age has increased from 30 to 36 years,
      with a greater proportion of calls from divers aged 50 years or older (from 2% to
      14%). The largest group of calls (37%) related to whether symptoms might be the
      result of decompression illness (DCI). DCI was considered to be the probable
      diagnosis in 17% of calls, and possible in a further 12%. Other common findings
      were barotrauma (11%) and questions regarding fitness to dive (15%). Older divers
      were more likely to call in relation to a medical problem. CONCLUSION:
      Interpretation of these data is qualitative but the prolonged collection period
      of 17 years allows some consideration of trends as to who calls the DES and why.

PMID- 22987461
TI  - Lower risk of decompression sickness after recommendation of conservative
      decompression practices in divers with and without vascular right-to-left shunt.
AB  - INTRODUCTION: A vascular right-to-left shunt (r/l shunt) is a well-known risk
      factor for the development of decompression sickness (DCS). No studies to date
      have examined whether divers with a history of DCS with or without a r/l shunt
      have a reduced risk of suffering recurrent DCS when diving more conservative dive
      profiles (CDP). METHODS: Twenty-seven divers with a history of DCS recommended
      previously to dive more conservatively were included in this study and
      retrospectively interviewed by phone to determine the incidence of DCS
      recurrence. RESULTS: Twenty-seven divers performed 17,851 dives before
      examination in our department and 9,236 after recommendations for conservative
      diving. Mean follow up was 5.3 years (range 0-11 years). Thirty-eight events of
      DCS occurred in total, 34 before and four after recommendation of CDP. Four
      divers had a closure of their patent foramen ovale (PFO). A highly significant
      reduction of DCS risk was observed after recommendation of CDP for the whole
      group as well as for the sub-groups with or without a r/l shunt. A significant
      reduction of DCS risk in respect to r/l shunt size was also observed. DISCUSSION:
      This study indicates that recommendations to reduce nitrogen load after DCS
      appear to reduce the risk of developing subsequent DCS. This finding is
      independent of whether the divers have a r/l shunt or of shunt size. The risk of
      suffering recurrent DCS after recommendation for CDP is less than or equal to an
      unselected cohort of divers. CONCLUSION: Recommendation for CDP seems to
      significantly reduce the risk of recurrent DCS.

PMID- 22987462
TI  - Provisional report on diving-related fatalities in Australian waters 2007.
AB  - INTRODUCTION: An individual case review of diving-related deaths reported as
      occurring in Australia in 2007 was conducted as part of the on-going Divers Alert
      Network (DAN) Asia-Pacific dive fatality reporting project. METHOD: The case
      studies were compiled using reports from witnesses, the police and coroners. In
      each case, the particular circumstances of the accident and details from the post
      mortem examination, where available, are provided. RESULTS: In total, there were
      19 reported fatalities, comprising three females and 16 males. Nine of the deaths
      occurred while snorkelling and/or breath-hold diving, eight while open-circuit
      scuba diving, one while using a closed-circuit rebreather, and one while using
      surface-supply breathing apparatus. Cardiac-related issues were thought to have
      contributed to the deaths of at least three but possibly up to six snorkel divers
      and possibly two scuba divers. One diver is believed to have died as a result of
      immersion pulmonary oedema of diving. Six of the compressed-gas divers were very
      inexperienced, three being certified within 14 days prior and dying while under
      the guidance of an instructor. CONCLUSIONS: Inexperience, pre-existing medical
      conditions and buoyancy issues were highlighted in several deaths in this series.

PMID- 22987464
TI  - Ultrasound under pressure.

PMID- 22987463
TI  - The use of deep tables in the treatment of decompression illness: the Hyperbaric
      Technicians and Nurses Association 2011 Workshop.
AB  - In August 2011, a one-day workshop was convened by the South Pacific Underwater
      Medicine Society and the Hyperbaric Technicians and Nurses Association to examine
      the use of deep recompression treatment tables for the treatment of decompression
      illness in Australia and New Zealand. The aim of the workshop was to develop a
      series of consensus statements to guide practice around the region. The workshop
      chose to focus the discussion on the use of 405 kPa (30 msw) maximum depth tables
      using helium-oxygen breathing periods, and covered indications, staffing and
      technical requirements. This report outlines the evidence basis for these
      discussions and summarises the series of consensus statements generated. These
      statements should assist hyperbaric facilities to develop and maintain
      appropriate policies and procedures for the use of such tables. We anticipate
      this work will lead to the formulation of a standard schedule for deep
      recompression to be developed at a future workshop.

PMID- 22987465
TI  - Control groups in hyperbaric trials.

PMID- 22987466
TI  - [Understanding needs of people with Multiple Sclerosis. Perspective of patients
      and significant others in the German-speaking part of Switzerland].
AB  - Since there is no data available about the needs of people living with Multiple
      Sclerosis and significant others in Switzerland a questionnaire based cross
      sectional study was conducted with 878 patients and 615 family caregivers. This
      Swiss study used the addresses from the Swiss Multiple Sclerosis Society. The
      response rate was 35.2 % for patients and 70.1 % for significant others. Data
      analysis included descriptive and inferential statistics. Results showed that
      information needs are most important followed by consultation. 42.4 % of patients
      and 39.2  % of family caregivers need more information about alternative
      treatment options and 34.4 %, resp. 36.6  % about actual research results. For
      39.5  % of patients, the possibility of using of their wheelchair in public is
      insufficient. Approximately a third of patients need more consultation in order
      to better manage cognitive impairment and fatigue. 30.9 % of family caregivers
      need more consultations in order to better manage their feelings of burden.
      Influencing factors of patients' need for consultation about fatigue are health
      status, quality of life, and anxiety. Patients' need for consultation about their
      management of cognitive impairment was influenced by health status, medication,
      and their ability of dealing with constraints and anxiety. The results showed
      that an enhancement of the quality of treatment and care based on patients' and
      family caregivers' needs are urgently needed.

PMID- 22987467
TI  - [A micro-education programme for breastfeeding women: a pilot study to
      investigate the educations' effect on injured and painful nipples].
AB  - Injured and painful nipples are frequently occurring events in nursing women
      during the first days after giving birth. These problems often result in a
      premature termination of breastfeeding despite the mother's wish to nurse.
      Unsystematic instructions given to women regarding correct breastfeeding increase
      the risk that these complications will arise. The objective of the study was to
      investigate the effect of a systematic micro-education programme for nursing
      women by means of a pilot study or a quasi-experiment. The study included 100
      mother and child pairs each in the experimental group and in the control group (N
      = 200). The pain experienced by all women during nursing was measured using the
      Visual Analogue Scale (VAS) and the degree of injury to the nipples after nursing
      was measured with a tool specially developed for this purpose, the Nipple Wound
      Score (NWS). Women who received instructions by means of the micro-education
      programme exhibited significantly less injured nipples (on the third day:
      experimental group 55 % and control group 77 %, p < 0.00; on the fourth day: 56 %
      and 80 %, p < 0.00).No differences were observed between the study groups in
      regard to the occurrence of pain (on the fourth day p = 0.68). The variables of
      birthing method, parity, age or nationality of the women had no effect on the
      degree of injury of the nipples or on the intensity of pain. The results of this
      pilot study suggest that repeated micro-education for breastfeeding women should
      be implemented during the first days after giving birth.

PMID- 22987468
TI  - [Oncological patients' decision making processes concerning their pain medication
      at home: a qualitative secondary analysis].
AB  - Unrelieved pain affects up to 75 % of cancer patients. Possible reasons for the
      undertreatment of pain are, amongst others, patient-related barriers towards
      cancer pain management. However the way patients decide on the use of analgesics
      remains unclear. The purpose of this qualitative study was to explore decision
      making processes of four women and four men with diverse cancers concerning their
      pain medications. Audiotaped protocols of the 10-week-intervention and interviews
      of the PEINCA-pilot study provided data for a secondary analysis. This pilot
      study was conducted at a comprehensive cancer centre in Germany to test the
      German version of a cancer pain self-management intervention to enhance oncology
      patients' pain self-management for the first time. The data of purposively
      selected patients were analysed using content analysis. The results showed that
      these patients were very ambivalent about their analgesic use. The need to
      relieve severe pain conflicted with the desire to avoid opioids at any price.
      Decisions were reconsidered and overturned even after good experiences with
      analgesics. This study seems to provide a first look into decision-making
      processes over 10 weeks during a self-management education. Individually tailored
      counselling by a professional within the education programme helped the patients
      adopt new attitudes towards analgesics and gradually reduce their pain levels.
      Previous experiences of the patients and their possible ambivalence towards
      analgesics should be considered in a pain therapy, and patients should be coached
      by professionals.

PMID- 22987469
TI  - [The experience and coping of primary coronary intervention: a review of
      qualitative studies].
AB  - Over the years, primary percutaneous coronary intervention (PCI) has been
      established as a superior emergency treatment for ST-elevation myocardial
      infarction (STEMI) in comparison to intravenous thrombolysis. This literature
      review is based on four qualitative studies and describes how patients with STEMI
      experience the acute phase of myocardial infarction with immediate PCI and how it
      affects their early recovery phase. Qualitative analysis in this study followed
      Noblit and Hare's method of metasynthesis. The results ascertained a correlation
      between the seriousness of the diagnosis and the quickness of treatment. PCI
      offers patients immediate pain relief. The patients' trust in the professionalism
      of the medical team becomes apparent through their passive participation during
      treatment. Although patients experience a quick recovery after PCI, they lack
      adequate information to completely understand their diagnosis of myocardial
      infarction. The patients feel having been cured by PCI, but continue to fear
      another myocardial infarction. The patients try to establish a new life routine,
      but report a lack of continuity in their healthcare provision. The results
      indicate that after PCI patients experience recurring changes of their
      perspective regarding their illness and well-being. Therefore, a comprehensive,
      sustained, and more patient-oriented approach regarding treatment in the early
      recovery phase is recommended.

PMID- 22987470
TI  - [Does nursing care planning improve general practice? Study of 100 nursing
      documentations].

PMID- 22987471
TI  - [The nursing process 25 years ago and today].

PMID- 22987472
TI  - [Validation and implementation of the comprehensive ICF Core Sets for patients
      with rehabilitation needs in the acute hospital].

PMID- 22987473
TI  - Early registration of diffusion tensor images for group tractography of dystonia
      patients.
AB  - PURPOSE: To make a group comparison of diffusion tensor imaging (DTI) results of
      dystonia patients and controls to reveal occult pathology. We propose using an
      early registration method that produces sharper group images and enables us to do
      group tractography. MATERIALS AND METHODS: Twelve dystonia patients manifesting
      the disease, seven nonmanifesting dystonia mutation carriers (DYT1 and DYT6 gene
      mutations), and eight age-matched normal control subjects were imaged for a
      previous study. Early and late registration methods for DTI were compared. An
      early registration technique for a super set was proposed, in which the diffusion
      weighted images were registered to a template, gradient vectors were reoriented
      for each subject, and they were combined into a super set before tensor
      calculation. The super set included images from all subjects and was useful for
      group comparisons. We used results obtained from the early registration of a
      super set for group analysis of tracts using the deterministic fiber-tracking
      technique. RESULTS: In dystonia mutation carriers, we detected fewer fibers in
      the cerebello-thalamo-cortical pathways. This result agrees well with the
      findings of a previous study that utilized a probabilistic tractography method
      and demonstrated that gene carriers have less fiber tracts in the disease
      involved pathway. CONCLUSION: This analysis visualized group level white matter
      fractional anisotropy and tract differences between dystonia patients and
      controls, and can be useful in understanding the pathophysiology of other
      nonfocal white matter diseases.

PMID- 22987474
TI  - Epstein-Barr virus presence in pediatric diffuse large B-cell lymphoma reveals a
      particular association and latency patterns: analysis of viral role in tumor
      microenvironment.
AB  - Non-Hodgkin's lymphoma represents 6-10% of pediatric malignancies, and diffuse
      large B-cell lymphoma (DLBCL) is one of the three major subtypes. The 2008 WHO
      classification included a new entity, Epstein-Barr virus (EBV)-positive DLBCL of
      the elderly, affecting patients >50 years. It has been demonstrated that EBV may
      play a role in tumor microenvironment composition, disturbing antitumor immune
      response and disease progression. As most studies were performed in adults, our
      aim was to assess EBV presence and latency pattern, as well as T-cell
      microenvironment in a pediatric DLBCL series of Argentina. The study was
      conducted on formalin-fixed paraffin-embedded biopsies from 25 DLBCL patients.
      EBV-encoded small nuclear early regions (EBERs) expression was performed by in
      situ hybridization, whereas EBV gene expression was analyzed using real-time PCR.
      Epstein-Barr virus latent membrane proteins (LMP)1, LMP2A, CD3, CD4, CD8 and
      Foxp3 expression were assessed by immunohistochemistry (IHC). Forty percent of
      cases showed EBV expression, with a significantly higher incidence among patients
      <10 years (p = 0.018), and with immunosuppressed (p = 0.023). T-cell subsets were
      not altered by EBV presence. Full EBV latency antigen expression (latency type
      III) was the most frequently pattern observed, together with BZLF1 lytic gene
      expression. One patient showed II-like pattern (LMP1 without LMP2A expression).
      Based exclusively on IHC, some patients showed latency II/III (EBERs and LMP1
      expression) or I (EBERs only). These findings suggest that EBV association in our
      series was higher than the previously demonstrated for elderly DLBCL and that EBV
      latency pattern could be more complex from those previously observed. Therefore,
      EBV could be an important cofactor in pediatric DLBCL lymphomagenesis.

PMID- 22987475
TI  - Detection of respiratory viruses in asymptomatic children undergoing allogeneic
      hematopoietic cell transplantation.
AB  - Detection of respiratory viruses by molecular methods, in children without
      respiratory symptoms undergoing hematopoietic cell transplantation (HCT), has not
      been well described. A prospective study of 33 asymptomatic children detected
      respiratory viruses in 8 of 33 (24%) patients before HCT. Human rhinovirus (HRV)
      was detected in five patients, and human adenovirus (hADV) in three patients. Two
      additional patients shed HRV, and one shed human coronavirus (hCoV), post-HCT.
      Two patients had co-infections. Of the 11 asymptomatic patients where respiratory
      virus was detected, 3 (27%) later developed an upper respiratory tract infection,
      from the same virus.

PMID- 22987476
TI  - Hot water, UV-C and superatmospheric oxygen packaging as hurdle techniques for
      maintaining overall quality of fresh-cut pomegranate arils.
AB  - BACKGROUND: In recent years there has been increasing consumer pressure to avoid
      the use of agrochemicals such as chlorine on fresh plant products for extending
      their shelf life. The combined use of eco-sustainable techniques may be an
      alternative. The effect of hot water (HW), ultraviolet-C (UV-C) light and high
      oxygen packaging (HO) on the overall quality of fresh-cut pomegranate arils
      stored under modified atmosphere packaging (MAP) for up to 14 days at 5  degrees
      C was studied. RESULTS: Arils extracted manually, washed with chlorine (100 uL L
      1 NaClO, pH 6.5, 5  degrees C water), rinsed and drained were exposed to single
      or combined (double and triple) hurdle techniques. The HW treatment consisted of
      a 30 s immersion in water at 55  degrees C followed by air surface drying. A 4.54
      kJ m-2 dose was used for the UV-C treatment before packaging. Active MAP with
      initial 90 kPa O2 was used in the HO treatment. The respiration rate remained
      relatively constant throughout shelf life, with no differences among treatments.
      CO2 accumulation was higher within HO packages. HW induced a slight reduction in
      total soluble solids, while no changes in titratable acidity were found. HO
      treated arils had the highest phenolic content, while the lowest was found in HW
      treated arils. The lowest antioxidant activity was found in HW + UV-C + HO and
      the highest in UV-C + HO and HO treatments. HW alone or in combination with UV-C
      and HO inhibited mesophile, mould and yeast growth, while UV-C + HO was most
      effective for controlling yeast and mould growth. CONCLUSION: UV-C and HO either
      alone or in combination are promising techniques to preserve the quality of
      pomegranate arils for up to 14 days at 5  degrees C.

PMID- 22987477
TI  - Effective fixation of CO2 by iridium-catalyzed hydrosilylation.

PMID- 22987479
TI  - Brief report: Adult hippocampal precursor cells shorten S-phase and total cell
      cycle length during neuronal differentiation.
AB  - Cell cycle analyses of adult hippocampal neural stem and precursor cells in vivo
      are challenging, as there is no temporal or local discrimination of different
      precursor cell populations. All commonly used techniques to determine the cell
      cycle length of proliferating cells in the adult hippocampus do not allow
      discrimination between different cell types. Here, we introduce a novel procedure
      to precisely calculate cell cycle phase lengths of distinct precursor cell
      populations in vivo and thereby demonstrate a large heterogeneity of cell cycle
      kinetics within the pool of adult hippocampal precursor cells. Proliferating
      NeuroD1(+) cells exhibited a significantly faster S-phase progression (T(s) =
      10.1 +/- 0.6 hours) and shorter total cell cycle length (T(c) = 22.6 +/- 0.1
      hours) than NeuroD1(-) cells (T(s) = 13.5 +/- 0.8 hours, T(c) = 27.0 +/- 0.5
      hours; p < .05). Dividing glial fibrillary acidic protein (GFAP(+)) cells also
      showed significantly shorter mean T(s) of 9.7 +/- 0.6 hours and T(c) of 22.8 +/-
      0.5 hours compared to the rest of uncommitted NeuroD1(-) precursors (p < .01).
      Together, NeuroD1(+) neuronal progenitors and mitotic GFAP(+) radial glia-like
      cells divide significantly faster than amplifying neural progenitor cells by
      accelerating their S-phase. S-phase duration seems to determine cell cycle length
      in the adult hippocampus.

PMID- 22987478
TI  - Trait-level and momentary correlates of bulimia nervosa with a history of
      anorexia nervosa.
AB  - OBJECTIVE: Some investigators have suggested subtyping bulimia nervosa (BN) by
      anorexia nervosa (AN) history. We examined trait-level and momentary eating
      related and psychosocial factors in BN with and without an AN history. METHOD:
      Interview, questionnaire, and ecological momentary assessment data of eating
      related and psychological symptoms were collected from 122 women with BN,
      including 43 with (BN+) and 79 without an AN history (BN-). RESULTS: Body mass
      index (kg/m(2) ) was lower in BN+ than BN- (p = 0.001). Groups did not differ on
      trait-level anxiety, shape/weight concerns, psychiatric comorbidity, or dietary
      restraint; or on momentary anxiety, dietary restriction, binge eating, purging,
      or exercise frequency, or affective patterns surrounding binge/purge behaviors.
      Negative affect increased prior to exercise and decreased thereafter in BN+ but
      not BN-, although groups did not statistically differ. DISCUSSION: Results do not
      support formally subtyping BN by AN history. Exercise in BN+ may modulate
      negative affect, which could have important treatment implications.

PMID- 22987480
TI  - The signature of craniofacial deformation in fibrodysplasia ossificans
      progressiva.

PMID- 22987481
TI  - Preparation of stable low-oxidation-state group 14 element amidohydrides and
      hydride-mediated ring-expansion chemistry of N-heterocyclic carbenes.
AB  - Various low oxidation state (+2) group 14 element amidohydride adducts,
      IPr?EH(BH(3))NHDipp (E=Si or Ge; IPr=[(HCNDipp)(2)C:], Dipp=2,6-iPr(2)C(6)H(3)),
      were synthesized. Thermolysis of the reported adducts was investigated as a
      potential route to Si- and Ge-based clusters; however, unexpected
      transmetallation chemistry occurred to yield the carbene-borane adduct,
      IPr?BH(2)NHDipp. When a solution of IPr?BH(2)NHDipp in toluene was heated to 100 
      degrees C, a rare C-N bond-activation/ring-expansion reaction involving the bound
      N-heterocyclic carbene donor (IPr) transpired.

PMID- 22987482
TI  - First bite syndrome: case report of 3 patients treated with botulinum toxin and
      review of other treatment modalities.
AB  - BACKGROUND: First bite syndrome is an unexpected yet relatively common
      complication of surgeries involving the parapharyngeal space. It can have a
      significant effect on both the quality of life and physical health of affected
      patients. This study presents 3 cases of first bite syndrome treated with
      botulinum toxin and a review of the current literature on available treatment
      modalities for first bite syndrome. METHODS: Three patients with first bite
      syndrome were injected with 75 units of botulinum toxin into affected parotid
      glands, focusing on areas of greatest first bite pain. RESULTS: Two of 3 patients
      experienced complete relief of symptoms for 4 to 6 months. The third patient had
      significant decrease in pain at 4-month follow-up. CONCLUSIONS: Many treatments
      for first bite syndrome have been attempted including: dietary modification,
      pharmacological treatments, and surgical treatments. However, few have been
      successful. Botulinum toxin is a safe and effective treatment for this life
      altering and difficult to treat first bite syndrome.

PMID- 22987483
TI  - Protective roles of single-wall carbon nanotubes in ultrasonication-induced DNA
      base damage.
AB  - The overall level of ultrasonication-induced DNA damage is reduced in the
      presence of single-wall carbon nanotubes (SWCNTs), particularly for DNA lesions
      formed by one-electron reduction of intermediate radicals. The protective role of
      SWCNTs observed in this work suggests a contrary view to the general idea that
      carbon nanotubes have damaging effects on biomolecules.

PMID- 22987484
TI  - Reduced connexin43 expression correlates with c-Src activation, proliferation,
      and glucose uptake in reactive astrocytes after an excitotoxic insult.
AB  - In diverse brain pathologies, astrocytes become reactive and undergo profound
      phenotypic changes. Connexin43 (Cx43), the main gap junction channel-forming
      protein in astrocytes, is one of the proteins modified in reactive astrocytes.
      Downregulation of Cx43 in cultured astrocytes activates c-Src, promotes
      proliferation, and increases the rate of glucose uptake; however, so far there
      have been no studies examining whether this cascade of events takes place in
      reactive astrocytes. In this work, we analyzed this pathway after a cortical
      lesion induced by a kainic acid injection. As previously described, astrocytes
      reacted to the lesion with an increase in glial fibrillary acidic protein and a
      decrease in Cx43 expression. Some of these reactive astrocytes proliferated, as
      estimated by bromodeoxyuridine incorporation and cyclins D1 and D3 upregulation.
      In addition, the expression of the glucose transporter GLUT-3 and the enzyme
      responsible for glucose phosphorylation, Type II hexokinase (Hx-2), were induced
      in reactive astrocytes, suggesting an increased glucose uptake. Previous in vitro
      studies reported that c-Src is the link between Cx43 and glucose uptake and
      proliferation in astrocytes. Here, we found that c-Src activity increased in the
      lesioned area. c-Src activation and Cx43 downregulation preceded the peak of Hx-2
      and cyclin D3 expression, suggesting that c-Src could mediate the effect of Cx43
      on glucose uptake and proliferation in reactive astrocytes after an excitotoxic
      insult. Interestingly, we identify c-Src, GLUT-3, and Hx-2 in the signaling
      mechanisms involved in the reaction of astroglia to injury. Altogether these data
      contribute to identify new therapeutical targets to enhance astrocyte
      neuroprotective activities.

PMID- 22987486
TI  - Androgen receptor on the move: boarding the microtubule expressway to the
      nucleus.
AB  - Recent studies have shown that the microtubule-stabilizing drug paclitaxel, which
      is commonly used for the treatment of prostate cancer, inhibits signaling from
      the androgen receptor by inhibiting its nuclear accumulation downstream of
      microtubule stabilization. This mechanism is independent of paclitaxel-induced
      mitotic arrest and could provide an alternative mechanism of drug action that can
      explain its clinical activity. In this review, we highlight the importance of
      signaling and trafficking pathways that depend on intact and dynamic
      microtubules, and, as such, they represent downstream targets of microtubule
      inhibitors. We showcase prostate cancer, which is driven by the activity of the
      androgen receptor, as recent reports have revealed a connection between the
      microtubule-dependent trafficking of the androgen receptor and the clinical
      efficacy of taxanes. Identification and further elucidation of microtubule
      dependent tumor-specific pathways will help us better understand the molecular
      basis of clinical taxane resistance as well as to identify individual patients
      more likely to respond to treatment.

PMID- 22987487
TI  - HER2 overexpression renders human breast cancers sensitive to PARP inhibition
      independently of any defect in homologous recombination DNA repair.
AB  - HER2 overexpression in breast cancer confers increased tumor aggressiveness.
      Although anti-HER2 therapies have improved patient outcome, resistance ultimately
      occurs. PARP inhibitors target homologous recombination (HR)-deficient tumors,
      such as the BRCA-associated breast and ovarian cancers. In this study, we show
      that HER2+ breast cancers are susceptible to PARP inhibition independent of an HR
      deficiency. HER2 overexpression in HER2 negative breast cancer cells was
      sufficient to render cells susceptible to the PARP inhibitors ABT-888 and AZD
      2281 both in vitro and in vivo, which was abrogated by HER2 reduction. In
      addition, ABT-888 significantly inhibited NF-kappaB (p65/RelA) transcriptional
      activity in HER2+ but not HER2 negative breast cancer cells. This corresponded
      with a reduction in phosphorylated p65 and total IKKalpha levels, with a
      concomitant increase in IkappaBalpha. Overexpression of p65 abrogated cellular
      sensitivity to ABT-888, whereas IkappaBalpha overexpression reduced cell
      viability to a similar extent as ABT-888. Therefore, susceptibility of HER2+
      breast cancer cells to PARP inhibition may be because of inhibition of NF-kappaB
      signaling driven by HER2. Our findings indicate that PARP inhibitors may be a
      novel therapeutic strategy for sporadic HER2+ breast cancer patients.

PMID- 22987488
TI  - Antidiabetic drugs and kidney disease--recommendations of the Swiss Society for
      Endocrinology and Diabetology.
AB  - Patients with diabetes are at risk of early renal function decline. Therefore,
      kidney function needs monitoring at least once per year. Once the glomerular
      filtration rate (GFR) is less than 60 ml/min, the pharmacokinetics of
      antidiabetic drugs may be altered. Sulfonylurea and glinide therapies are
      associated with a risk of hypoglycaemia which is increased in the presence of
      renal impairment. Most sulfonylureas must be discontinued once GFR is <60 ml/min.
      Some glinides may be continued beyond this threshold, in particular repaglinide,
      which may be used in dialysis patients. In the absence of comorbidities,
      metformin can be continued at lower doses until a GFR of 45 ml/min, but must be
      withdrawn in case of dehydration or during the administration of a nephrotoxic
      drug including dye for radiological investigations. Glitazones may worsen water
      and sodium retention in patients with renal impairment. The pharmacokinetics of
      all DPP-IV inhibitors except linagliptin are altered with impaired renal
      function. Only sitagliptin, saxagliptin and linagliptin may be used in advanced
      kidney disease, but experience is as yet very limited. GLP-1 agonists are
      contraindicated in moderate to advanced kidney disease.

PMID- 22987490
TI  - [Transference interpretations and how they work: a systematic review].
AB  - In clinical theory transference interpretations represent a central therapeutic
      technique and a specific mechanism of change in psychodynamic psychotherapies.
      However, the empirical basis lags behind the theoretical considerations. This
      article reviews both the results of empirical research on transference
      interpretations and their definitions of the measures employed (systematic
      database search for the timespan 1970-2011). The empirical results are rather
      heterogeneous and in part contradictory. As it turns out, specific patient
      characteristics (e.g., the quality of object relations), the amount and quality
      of transference interpretations as well as the patients' immediate reaction all
      decisively influence the potency of the change of transference interpretations.
      Currently, it is not possible to develop clear therapeutic strategies based on
      previous findings. Careful use of transference interpretations is generally
      recommended. Various methods for measuring transference interpretations exist,
      but the definitions do not correspond completely. A standardization of
      definitions would increase the comparability and interpretability of findings and
      greatly improve concordance with theory.

PMID- 22987491
TI  - [ADHD across the lifespan - an update on research and practice].
AB  - ADHD can be regarded as a lifespan disorder. From biopsychosocial vantage point,
      ADHD leads to age-specific impairments, high psychological distress and is
      associated with a high occurrence of comorbid disorders. For this review, we
      summarize actual findings from epidemiological, neuroscientific and clinical
      studies to present an overview of ADHD-research. We discuss the proposed
      revisions for DSM-V criteria by comparing them with the present DSM-IV-TR
      criteria, with a focus on the implications for research and practice. In the
      second part of this paper, we present new findings from socioeconomic, diagnostic
      and therapeutic perspectives. There is evidence for a high economic burden that
      is indirectly caused by ADHD (e.g., production loss, material costs, higher
      accident rates). Consequently, there is a high demand for comprehensive
      diagnostic and therapeutic approaches. We present a summary of the latest
      available diagnostic instruments and therapeutic manuals. The results of research
      and practice show a growing support for a lifespan perspective on ADHD
      psychopathology. The burdens resulting from ADHD are evident in all age groups,
      which has led to establishing age-specific diagnostic and therapeutic materials.
      Although there is a lack in ADHD-specific healthcare in adulthood, this should be
      realized by structural changes in healthcare services.

PMID- 22987492
TI  - [Therapy Process Questionnaire (TPQ) - a combined explorative and confirmatory
      factor analysis and psychometric properties].
AB  - OBJECTIVES: This contribution looks at the factorial structure of the Therapy
      Process Questionnaire (TPQ), which is used for daily self-ratings of patients
      tested by internet-based ambulatory assessment devices. METHODS: A combined
      explorative and confirmatory factor analysis of the TPQ. The time-series data
      were generated by 149 patients treated in an inpatient setting. RESULTS: 23 out
      of 42 items included in the explorative version of the TPQ are represented onto
      five factors, which were identified by a first explorative factor analysis and
      then validated by a confirmative factor analysis. We report on the psychometric
      data of the subscales: internal consistency (Cronbach's alpha), mean of item
      intercorrelation, and mean of item discrimination indices. CONCLUSION: The TPQ is
      useful for a high-frequency and equidistant (daily) assessment of
      psychotherapeutic change processes.

PMID- 22987493
TI  - [Quality of life and satisfaction of family caregivers in palliative care -
      results of postmortem interviews with bereaved family members].
AB  - INTRODUCTION: Family caregivers play an important role in palliative care.
      However, the number of studies focussing on the quality of life of these family
      caregivers is limited. The current study evaluates quality of life and
      satisfaction with medical care in bereaved family members. MATERIAL AND METHODS:
      Comparisons were made between (1) male vs. female family caregivers (N = 44) and
      (2) bereaved family caregivers vs. general population (EORTC QLQ-C30).
      Furthermore, the satisfaction of the family caregivers with medical care was
      assessed after the death of their relatives (ZUF HOPE). The interviews were
      conducted between six and eight weeks following the death of the palliative
      patients. RESULTS: Regarding quality of life, bereaved family caregivers suffered
      from both reduced emotional functioning and general quality of life. Female
      caregivers had lower functional values and stronger symptoms of insomnia, fatigue
      and pain than male caregivers. Bereaved family caregivers had a lower quality of
      life than the general population. Retrospectively, family caregivers were very
      satisfied with most aspects of outpatient palliative care. The only aspect
      criticised by the bereaved family members was a lack of psycho-social support.
      CONCLUSION: Family caregivers need stronger support in order to prevent burnout
      and to improve outpatient care. In this context, gender differences must also be
      considered.

PMID- 22987494
TI  - [OPD in the hospital: an algorithm for structuring the diagnostic process with
      the Operationalized Psychodynamic Diagnostics OPD-2].
AB  - OBJECTIVES: Operationalized psychodynamic diagnostics OPD-2 is a diagnostic
      procedure that has proven to be valuable for psychotherapy. However, to date
      there has been only little discussion about the application context and any
      necessary adaptations to various clinical fields. METHODS AND RESULTS: The
      working group "Implementation of OPD in Clinical Practice" proposes an algorithm
      for the sequential and adapted use of OPD depending on the clinical context.
      CONCLUSION: Especially for patients who are primarily not open to receiving
      psychotherapy, e.g., in psychiatric hospitals or general hospitals, OPD can be an
      important basis for structuring motivating interventions. A stepwise procedure is
      proposed which is adapted to the usage of OPD in such contexts. Furthermore, also
      for these contexts, simplified ratings are proposed and discussed for the axes
      relationships, conflicts and structure. However, complete OPD remains recommended
      when determining the focus of a psychotherapeutic treatment.

PMID- 22987495
TI  - Comparison of cognitive-behaviour therapy with psychoanalytic and psychodynamic
      therapy for depressed patients - a three-year follow-up study.
AB  - OBJECTIVE: The study investigates the effectiveness of long-term psychotherapies.
      Cognitive-behaviour therapy was compared with psychoanalytic and psychodynamic
      therapy in the treatment of patients with a primary diagnosis of unipolar
      depression. METHOD: In a prospective, quasi-experimental design 100 patients were
      compared at pre- and post-treatment and three-year follow-up. Outcome measures
      were the Beck Depression Inventory and Global Severity Index for measuring
      symptoms, the Inventory of Interpersonal Problems and the Social Support
      Questionnaire for measurement of social-interpersonal functioning, and the INTREX
      Introject Questionnaire for measuring personality structure. Comparative
      effectiveness of the experimental groups was analyzed using mixed models.
      RESULTS: We found significant outcome differences between psychoanalytic therapy
      and cognitive-behaviour therapy in depressive and global psychiatric symptoms,
      partly social-interpersonal and personality structure at three-year follow-up.
      Psychodynamic therapy was superior to cognitive-behaviour therapy in the
      reduction of interpersonal problems. CONCLUSION: Psychoanalytic therapy shows
      significantly longer-lasting effects compared to cognitive-behaviour therapy
      three years after termination of treatment, which is discussed as a dose-effect.

PMID- 22987496
TI  - Impact factors, open access, and 125 years of Angewandte Chemie.

PMID- 22987497
TI  - Multireference level set for the characterization of nuclear morphology in
      glioblastoma multiforme.
AB  - Histological tissue sections provide rich information and continue to be the gold
      standard for the assessment of tissue neoplasm. However, there are a significant
      amount of technical and biological variations that impede analysis of large
      histological datasets. In this paper, we have proposed a novel approach for
      nuclear segmentation in tumor histology sections, which addresses the problem of
      technical and biological variations by incorporating information from both
      manually annotated reference patches and the original image. Subsequently, the
      solution is formulated within a multireference level set framework. This approach
      has been validated on manually annotated samples and then applied to the TCGA
      glioblastoma multiforme (GBM) dataset consisting of 440 whole mount tissue
      sections scanned with either a 20 * or 40  * objective, in which, each tissue
      section varies in size from 40k  * 40k pixels to 100k   * 100k pixels.
      Experimental results show a superior performance of the proposed method in
      comparison with present state of art techniques.

PMID- 22987498
TI  - Technique for interference reduction in battery powered physiological monitoring
      devices.
AB  - This paper presents a novel simple method to identify and remove systematic
      interference in battery powered physiological monitoring devices. This
      interference is very typically introduced via fluctuations in the power supply
      voltage, caused by the nonideal output resistance of small batteries, when a
      transceiver chip changes operating modes. The proposed method is designed to have
      low computational complexity in order to potentially allow for low cost, real
      time implementations on low-power-based platforms, either in the system front or
      back end. Additionally, the paper provides guidelines on how to choose some of
      the operating conditions of the transceiver in order to minimize the effect of
      the interference through the application of the proposed method. Overall,
      successful performance is illustrated with experimental results obtained from an
      acoustic monitoring system, since this is considered to have specifications which
      are representative of most physiological monitoring devices.

PMID- 22987499
TI  - Center of mass acceleration feedback control of standing balance by functional
      neuromuscular stimulation against external postural perturbations.
AB  - This study investigated the use of center of mass (COM) acceleration feedback for
      improving performance of a functional neuromuscular stimulation control system to
      restore standing function to a subject with complete, thoracic-level spinal cord
      injury. The approach for linearly relating changes in muscle stimulation to
      changes in COM acceleration was verified experimentally and subsequently produced
      data to create an input-output map driven by sensor feedback. The feedback gains
      were systematically tuned to reduce upper extremity (UE) loads applied to an
      instrumented support device while resisting external postural disturbances. Total
      body COM acceleration was accurately estimated (>89% variance explained) using 3
      D outputs of two accelerometers mounted on the pelvis and torso. Compared to
      constant muscle stimulation employed clinically, feedback control of stimulation
      reduced UE loading by 33%. COM acceleration feedback is advantageous in
      constructing a standing neuroprosthesis since it provides the basis for a
      comprehensive control synergy about a global, dynamic variable and requires
      minimal instrumentation. Future work should include tuning and testing the
      feedback control system during functional reaching activity that is more
      indicative of activities of daily living.

PMID- 22987500
TI  - Chromosome stability in tonsillar squamous cell carcinoma is associated with
      HPV16 integration and indicates a favorable prognosis.
AB  - Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human
      papillomavirus (HPV) and chromosome instability. Data from cellular model systems
      are, however, controversial concerning a relation between HPV and chromosome
      instability development. Here we studied this association in 77 primary TSCC with
      known clinical outcome and cell cycle protein expression profiles. Thirty-two
      tumors (42%) showed HPV16-integration. All 77 cases were analyzed by fluorescence
      in situ hybridization using chromosome 1- and 7-specific centromere DNA probes to
      detect chromosome instability, indicated by the presence of chromosome imbalances
      and/or polyploidization for these chromosomes. In addition, eight HPV-positive
      dysplasias, seven of which were adjacent to a carcinoma, were analyzed. Disomy
      for chromosome 1 and 7 was present in 29 out of 77 TSCC (38%), of which 19 were
      HPV16-positive (p = 0.002). Aneusomy was observed in the remaining 48 TSCC, of
      which 13 were HPV-positive. Aneusomies correlated significantly with tobacco- and
      alcohol consumption (p = 0.001 and p = 0.016, respectively) and a higher T-stage
      (p = 0.018). Both HPV-positivity and chromosome disomy were significantly
      associated with a favorable disease-free survival (p = 0.001 and p = 0.025,
      respectively). Particularly in the HPV16-positive group chromosome instability is
      a very strong indicator for an unfavorable prognosis (p = 0.032). In the
      dysplasias an identical HPV and chromosome copy number status was identified as
      in the adjacent tumors. We conclude that HPV-positive TSCC and their precursor
      lesions are more often genetically stable than HPV-negative lesions and that
      these tumors are associated with a favorable prognosis. Chromosome instability is
      an indicator for unfavorable prognosis, particularly in the HPV-positive patient
      group.

PMID- 22987501
TI  - Links between psychopathological symptoms and disordered eating behaviors in
      overweight/obese youths.
AB  - OBJECTIVE: Among overweight and obese youths, rates of depression, anxiety
      disorders, attention-deficit/hyperactivity disorder (ADHD), and oppositional
      defiant disorder (ODD) are elevated. We analyze whether these emotional and
      behavioral problems are associated with specifically disordered eating pattern.
      METHOD: Participants in the study were 128 overweight and obese
      children/adolescents (BMI: m = 29.3, s = 4.5; BMI-SDS: m = 2.5, s = 0.4) between
      8 and 15 years. Structured psychiatric assessments were conducted adopting a
      multimethod, multiinformant approach. RESULTS: Children/adolescents with ODD
      symptoms showed increased eating in response to external cues and binge eating.
      ADHD symptoms were not associated with disordered eating behaviors.
      Children/adolescents with symptoms of depression and anxiety showed emotional and
      binge eating. In particular, overweight girls with symptoms of depression showed
      restrained eating. DISCUSSION: Our results point to specific eating problems in
      overweight/obese children with ODD and depression/anxiety symptoms. The findings
      could help to tailor interventions to optimally meet the specific needs of
      overweight children with emotional and behavioral problems.

PMID- 22987502
TI  - Growth retardation, intellectual disability, facial anomalies, cataract, thoracic
      hypoplasia, and skeletal abnormalities: a novel phenotype.
AB  - We report on a 14-year-old girl with growth deficiency, microcephaly,
      intellectual disability, distinctive dysmorphic features (bulbous nose with wide
      nasal base, hypotelorism, deeply set eyes, protruding cupped ears, and thick
      lower lip), cataract, pigmentary retinopathy, hypoplastic thorax, kyphoscoliosis,
      and unusual skeletal changes but without chromosomal imbalances detected by array
      CGH who probably represents a novel phenotype.

PMID- 22987503
TI  - ATP conditions intestinal epithelial cells to an inflammatory state that promotes
      components of DC maturation.
AB  - Intestinal epithelial cells (IECs) normally promote the development of gut
      resident tolerogenic dendritic cells (DCs) and regulatory T cells, but how this
      process is altered in inflammatory bowel disease is not well characterized.
      Recently, we published that the cell injury signal ATP modulates IEC chemokine
      responses to the TLR5 ligand flagellin and exacerbates colitis in the presence of
      flagellin. We hypothesized that ATP switches these IECs from tolerogenic to
      proinflammatory, enhancing DC activation and immune responses to commensal
      antigens. Here, we report that ATP enhanced murine IEC production of KC, IL-6,
      TGF-beta, and thymic stromal lymphopoietin in response to TLR1/2 stimulation by
      Pam(3) CSK(4)  (PAM). Moreover, supernatants from IECs stimulated with ATP+PAM
      enhanced expression of CD80 on bone marrow derived dendritic cells, and increased
      their production of IL-12, IL-6, IL-23, TGF-beta, and aldh1a2, suggesting a
      Th1/Th17 polarizing environment. DCs conditioned by stressed IECs stimulated an
      enhanced recall response to flagellin and supported the expansion of IFN-gamma(+)
      and IL-17(+)  memory T cells. Lastly, colonic administration of nonhydrolysable
      ATP increased production of IL-6 and Cxcl1 (KC) by IECs. These findings indicate
      that ATP influences the response of IECs to TLR ligands and biases the maturation
      of DCs to become inflammatory.

PMID- 22987504
TI  - Epithelial to mesenchymal transition as a portal to stem cell characters embedded
      in gene networks.
AB  - Cells can transit between a range of stable epithelial and mesenchymal states and
      this has allowed the evolution of complex body forms. Epithelial to mesenchymal
      transition (EMT) and its reverse, mesenchymal to epithelial transition (MET),
      occur sequentially in development and organogenesis. EMT often accompanies
      transitions between stem-like cells and their more differentiated progeny, as
      occurs at gastrulation, although the relevance of this had not been clarified.
      New findings from the cancer and cell reprogramming fields suggest that EMT and
      MET can act as essential portals to stem cell character. Here, we review these
      findings in the broader context of EMT and MET with emphasis on stem cell
      biology. Using the heart as an example, we also explore the potential role of
      EMT/MET in organ regeneration. Understanding EMT and MET at a network level will
      give us new tools to probe stem cell character and enhance tissue repair.

PMID- 22987505
TI  - Sterically hindered o-quinone annulated with dithiete: a molecule comprising
      diolate and dithiolate coordination sites.
AB  - A new stable sterically hindered o-quinone annelated with a 1,2-dithiete ring was
      prepared by using mild conditions. The skeleton of the compound comprises diolate
      and dithiolate functions that have the potential to bind metals leading to the
      corresponding complexes. The reactivity of this compound as a ligand with respect
      to both coordination sites was studied. Reactions with metals indicate that the o
      quinone function is reduced in the first stage to give semiquinonate and
      catecholate complexes. The dithiolate coordination site was involved in the
      reaction in a few cases only after diolate was bound. A trinuclear manganese
      complex with coordination on both sites was obtained and characterized by EPR
      spectroscopy. The electrochemical study of this quinone fused with dithiete is
      reported.

PMID- 22987506
TI  - Microbiological aspects and shelf life of processed seafood products.
AB  - BACKGROUND: Fresh fish and seafoods are very perishable products mainly owing to
      microbial activity of specific spoilage micro-organisms. Application of hurdle
      technology leads to a variety of processed products with extended shelf life. In
      this study, sensory evaluation and microbiological analysis were carried out on
      17 processed seafood products stored at 4  degrees C to determine their shelf
      life and the predominant spoilage micro-organisms. RESULTS: Shelf life determined
      by sensory analysis varied from 66 to 180 days depending on the product. The
      cause of spoilage for most of the products was the development of off
      flavours/off-odours, while two products were rejected owing to oil
      discolouration. Pseudomonads were in most cases below detection limit. H2S
      producing bacteria, Brochothrix thermosphacta and Enterobacteriaceae were below
      detection limit throughout the experiment. The predominant spoilage micro
      organisms were lactic acid bacteria and yeasts. Hygiene indicators such as
      Staphylococcus spp. and total coliforms were also below detection limit in all
      samples. CONCLUSION: Primarily the initial pH and secondarily the NaCl content
      determined shelf life duration. Under the applied conditions, lactic acid
      bacteria and yeasts predominated. The contribution of chemical oxidation and/or
      autolysis to spoilage and shelf life might be important for most of the products.

PMID- 22987507
TI  - High-throughput arrays for rapid characterization of solution-processable
      transparent conducting electrodes.

PMID- 22987508
TI  - Influence of study sponsorship on head and neck cancer randomized trial results.
AB  - BACKGROUND: The purpose of this study was to identify associations between study
      sponsorship and the methodological quality and published outcomes of head and
      neck cancer randomized controlled trials (RCTs). METHODS: We systematically
      searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled
      Trials for qualified RCTs, evaluating journal impact factor (IF), Jadad score
      (measure of study quality), and results favoring or not favoring experimental
      therapy. RESULTS: Of 118 RCTs, the most common sponsor was government (38; 32%),
      followed by nonprofit organizations (30; 25%) and industry (26; 22%). Industry
      supported RCTs were associated with publication in journals with higher IF
      compared with RCTs without industry support (p = .013). Government-supported RCTs
      were associated with higher mean Jadad score (p = .026) and results favoring
      experimental therapy (p = .034). CONCLUSIONS: Government-supported, but not
      industry-supported, RCTs were significantly associated with positive study
      results. These findings may be confounded by broadly applied definitions of
      sponsorship.

PMID- 22987509
TI  - Multi-modal image registration based on gradient orientations of minimal
      uncertainty.
AB  - In this paper, we propose a new multi-scale technique for multi-modal image
      registration based on the alignment of selected gradient orientations of reduced
      uncertainty. We show how the registration robustness and accuracy can be improved
      by restricting the evaluation of gradient orientation alignment to locations
      where the uncertainty of fixed image gradient orientations is minimal, which we
      formally demonstrate correspond to locations of high gradient magnitude. We also
      embed a computationally efficient technique for estimating the gradient
      orientations of the transformed moving image (rather than resampling pixel
      intensities and recomputing image gradients). We have applied our method to
      different rigid multi-modal registration contexts. Our approach outperforms
      mutual information and other competing metrics in the context of rigid multi
      modal brain registration, where we show sub-millimeter accuracy with cases
      obtained from the retrospective image registration evaluation project.
      Furthermore, our approach shows significant improvements over standard methods in
      the highly challenging clinical context of image guided neurosurgery, where we
      demonstrate misregistration of less than 2 mm with relation to expert selected
      landmarks for the registration of pre-operative brain magnetic resonance images
      to intra-operative ultrasound images.

PMID- 22987510
TI  - An efficient optimization framework for multi-region segmentation based on
      Lagrangian duality.
AB  - We introduce a multi-region model for simultaneous segmentation of medical
      images. In contrast to many other models, geometric constraints such as inclusion
      and exclusion between the regions are enforced, which makes it possible to
      correctly segment different regions even if the intensity distributions are
      identical. We efficiently optimize the model using a combination of graph cuts
      and Lagrangian duality which is faster and more memory efficient than current
      state of the art. As the method is based on global optimization techniques, the
      resulting segmentations are independent of initialization. We apply our framework
      to the segmentation of the left and right ventricles, myocardium and the left
      ventricular papillary muscles in magnetic resonance imaging and to lung
      segmentation in full-body X-ray computed tomography. We evaluate our approach on
      a publicly available benchmark with competitive results.

PMID- 22987511
TI  - Peripapillary atrophy detection by sparse biologically inspired feature manifold.
AB  - Peripapillary atrophy (PPA) is an atrophy of pre-existing retina tissue. Because
      of its association with eye diseases such as myopia and glaucoma, PPA is an
      important indicator for diagnosis of these diseases. Experienced ophthalmologists
      are able to determine the presence of PPA using visual information from the
      retinal images. However, it is tedious, time consuming and subjective to examine
      all images especially in a screening program. This paper presents biologically
      inspired feature (BIF) for the automatic detection of PPA. BIF mimics the process
      of cortex for visual perception. In the proposed method, a focal region is
      segmented from the retinal image and the BIF is extracted. As BIF is an
      intrinsically low dimensional feature embedded in a high dimensional space, it is
      not suitable to measure the similarity between two BIFs directly based on the
      Euclidean distance. Therefore, it is necessary to obtain a suitable mapping to
      reduce the dimensionality. In this paper, we explore sparse transfer learning to
      transfer the label information from ophthalmologists to the sample distribution
      knowledge contained in all samples. Selective pair-wise discriminant analysis is
      used to define two strategies of sparse transfer learning: negative and positive
      sparse transfer learning. Experimental results show that negative sparse transfer
      learning is superior to the positive one for this task. The proposed BIF based
      approach achieves an accuracy of more than 90% in detecting PPA, much better than
      previous methods. It can be used to save the workload of ophthalmologists and
      thus reduce the diagnosis costs.

PMID- 22987512
TI  - Regulation of microglia activation and deactivation by nuclear receptors.
AB  - Microglia cells function as sentinels for innate immunity in the central nervous
      system (CNS). To perform this function, microglia express a diverse set of
      pattern recognition receptors (PRRs) for pathogen-associated molecular patterns
      (PAMPs) that include Toll-like receptors (TLRs) and inflammasomes. Several
      members of the TLR and inflammasome family also recognize endogenously derived
      molecules that are generated as a consequence of tissue injury or other
      pathological processes. Recognition of PAMPs or endogenous ligands by PRRs in
      microglia induces the robust activation of innate immune responses leading to the
      production of proinflammatory mediators and the activation of adaptive immunity.
      Activation of microglia is essential for clearance of infection and repair of
      tissue injury. However, uncontrolled inflammatory responses of microglia are also
      thought to contribute to the severity of many neurodegenerative diseases. Thus,
      activation of microglia must be properly and tightly regulated to maintain normal
      tissue homeostasis. Several mechanisms have been identified that appear to
      function in the active maintenance of quiescence under normal conditions and/or
      re-establish this state following resolution of infection or injury. These
      mechanisms involve communication with neurons and other glia through secreted
      molecules or surface expressing receptors as well as actions of members of the
      nuclear receptor (NR) superfamily of transcription factors. Here, we review
      recent advances in our understanding of the regulation of microglia activation
      and deactivation with a focus on counter-regulation of microglia activation by
      nuclear receptors.

PMID- 22987513
TI  - Organic contaminants of emerging concern in sediments and flatfish collected near
      outfalls discharging treated wastewater effluent to the Southern California
      Bight.
AB  - To investigate the occurrence and bioaccumulation of organic contaminants of
      emerging concern (CECs) near four major wastewater ocean outfalls in the Southern
      California Bight, more than 75 pharmaceutical and personal care products, current
      use pesticides, and industrial/commercial chemicals were analyzed in sediment and
      liver tissues of hornyhead turbot (Pleuronichthys verticalis) using gas and
      liquid chromatography-mass spectrometry. Although most CECs targeted were
      infrequently detected or not detectable, triclosan, 4-nonylphenol (4-NP) and
      bis(2-ethylhexylphthalate) were detected in all sediments at median (maximum)
      concentrations of 5.1 (8.6), 30 (380), and 121 (470) ug/kg, respectively. In the
      liver, 4-NP and polybrominated diphenyl ether (PBDE) congeners 47 and 99 were
      detected in >90% of samples at median (maximum) concentrations of 85 (290) and
      210 (480) ug/kg, respectively. The sedative diazepam was detected in all liver
      samples, but was infrequently detected in sediments. Sediment and liver
      concentrations across outfall locations ranged over several orders of magnitude
      and were elevated relative to a reference site. Relative to sediment,
      accumulation in liver of PBDEs 47 and 99 was comparable to that for legacy
      organochlorines, confirming their high bioaccumulation potential and suggesting
      their inclusion in future tissue monitoring studies. Mean tissue PBDE and
      diazepam concentrations were higher in livers from male versus female P.
      verticalis, suggesting that gender differences also be considered in designing
      such studies.

PMID- 22987514
TI  - Thyroid function and serum electrolytes: does an association really exist?
AB  - BACKGROUND: Thyroid hormone is a central regulator of body functions. Disorders
      of thyroid function are considered to be a cause of electrolyte disorders. Only
      few data on the association between thyroid function and electrolyte disorders
      exists. METHODS: In the present retrospective analysis data from all patients
      admitted to the Department of Emergency Medicine of a university hospital who had
      measurements of thyroid function (TSH, fT(3), fT(4)) and electrolytes were
      included. RESULTS: 9,012 patients with measurement of TSH and electrolytes were
      available. 86% of patients had normal, 4% suppressed and 10% elevated TSH. Serum
      sodium was significantly lower in patients with high TSH levels (p <0.01). There
      was a significant correlation between serum TSH and phosphate level (p <0.05).
      Phosphate levels were higher in patients with elevated TSH than in patients with
      normal TSH (p <0.01). Serum calcium and magnesium correlated significantly with
      TSH (p <0.05). fT(3) levels correlated significantly with calcium (p <0.05).
      Hyponatraemia was present in 14% of patients with high TSH and was significantly
      more common than in the group with normal TSH levels of which 9% had
      hyponatraemia (p <0.01). Hypokalaemia was more common in the group with elevated
      TSH than in those with normal TSH (14 versus 11%, p = 0.016). Hyperkalaemia was
      more common in the group with high TSH levels (7%) than in those with normal TSH
      (7 vs. 4%, p <0.01). CONCLUSION: An association between thyroid function and
      electrolyte disorders seems to exist, although it is probably only relevant in
      marked hypo-/hyperthyroidism.

PMID- 22987515
TI  - The impact of chemical pollution on biodiversity and ecosystem services: the need
      for an improved understanding.

PMID- 22987516
TI  - Adaptation to global climate change--A bandage as the guillotine descends.

PMID- 22987517
TI  - Transitioning sediment quality assessment into regulations: Challenges and
      solutions in implementing California's sediment quality objectives.
AB  - Development and promulgation of sediment quality criteria represents a
      substantial challenge for water quality agencies. Unlike water quality programs
      that rely on individual chemical thresholds to assess water quality, the complex
      processes affecting contaminant bioavailability in sediments preclude the use of
      contaminant concentrations to independently assess impacts or identify cause.
      Various multiple line of evidence approaches (e.g., sediment quality triad) have
      been developed for sediment quality assessment, but such frameworks are rarely
      fully incorporated into statewide regulatory programs due to a lack of
      standardized and validated tools. In 2003, California's State Water Resources
      Control Board (State Water Board) initiated development of sediment quality
      criteria and an assessment framework that required the developers to resolve many
      challenging technical and policy related issues to the satisfaction of
      stakeholders, scientists, and the general public. The first part of this
      multiyear effort has been completed and resulted in the development and
      validation of an integrated collection of tools, thresholds, and a data
      interpretation framework for assessing sediment contamination impacts on benthic
      community condition. The State Water Board's narrative sediment quality criteria
      and assessment framework became effective in 2009, following US Environmental
      Protection Agency approval. The results of this effort are described in a series
      of 6 articles published in this issue of Integrated Environmental Assessment and
      Management. The articles describe: 1) a multiple line of evidence framework for
      data integration and assessment, 2) calibration and evaluation of sediment
      quality guidelines for predicting toxic responses, 3) development and evaluation
      of sediment quality guidelines with respect to benthic macrofauna responses, 4)
      selection of toxicity test methods and thresholds, 5) identification and
      characterization of benthic community assemblages, 6) the effect of sampling
      methods on benthic community assessment, and 7) recommendations on improving the
      assessment of contaminant exposure in sediment quality assessment. This
      collection of articles illustrates the steps needed to improve the scientific
      foundation for sediment quality assessment in regulatory applications.

PMID- 22987519
TI  - Metal contamination and pollution in China: Where are we now?

PMID- 22987518
TI  - Habitat-related benthic macrofaunal assemblages of bays and estuaries of the
      western United States.
AB  - Data from 7 coastwide and regional benthic surveys were combined and used to
      assess the number and distribution of estuarine benthic macrofaunal assemblages
      of the western United States. Q-mode cluster analysis was applied to 714 samples
      and site groupings were tested for differences in 4 habitat factors (latitude,
      salinity, sediment grain size, and depth). Eight macrofaunal assemblages,
      structured primarily by latitude, salinity, and sediment grain size, were
      identified: (A) Puget Sound fine sediment, (B) Puget Sound coarse sediment, (C)
      southern California marine bays, (D) polyhaline central San Francisco Bay, (E)
      shallow estuaries and wetlands, (F) saline very coarse sediment, (G) mesohaline
      San Francisco Bay, and (H) limnetic and oligohaline. The Puget Sound, southern
      California, and San Francisco Bay assemblages were geographically distinct, while
      Assemblages E, F and H were distributed widely along the entire coast. A second Q
      mode cluster analysis was conducted after adding replicate samples that were
      available from some of the sites and temporal replicates that were available for
      sites that were sampled in successive years. Variabilities due to small spatial
      scale habitat heterogeneity and temporal change were both low in Puget Sound, but
      temporal variability was high in the San Francisco estuary where large
      fluctuations in freshwater inputs and salinity among years leads to spatial
      relocation of the assemblages.

PMID- 22987521
TI  - Humility is not enough: An extension of Cairns (2012).

PMID- 22987522
TI  - Third-hand tobacco smoke: Significant vector for PAH exposure or non-issue?

PMID- 22987523
TI  - What to do with NOECS/NOELS--prohibition or innovation?

PMID- 22987524
TI  - Comment on Fox et al. (2012): What to do with NOECs/NOELs.

PMID- 22987525
TI  - Reluctant comment on Fox et al. (2012): On being dragged into the NOEC squabble.

PMID- 22987528
TI  - Immigration and its impact on daily occupations: a scoping review.
AB  - Immigrants often adopt new and unfamiliar occupations in an attempt to adapt to
      their new culture. Occupations provide a means for participation in the host
      country and play a significant role in formulating a person's identity. This
      scoping review sought to identify the current knowledge on immigration and its
      impact on occupations. A scoping review for peer-reviewed articles published
      between 2000 and 2010 in English or French was completed. Thirty-six articles met
      the inclusion criteria. Four themes were identified: 1) role change; 2) work; 3)
      identity; and 4) health and well-being. Limitations include the lack of a
      consistent definition of occupation, research primarily being conducted in the
      North American context and the limited number of occupational therapy based
      articles. Future research should focus on a systematic review of the lived
      experiences of immigrants and their occupational contexts, and how this can
      inform policy development.

PMID- 22987529
TI  - Modeling Human Control of Self-Motion Direction With Optic Flow and Vestibular
      Motion.
AB  - In this paper, we investigate the effects of visual and motion stimuli on the
      manual control of one's direction of self-motion. In a flight simulator, subjects
      conducted an active target-following disturbance-rejection task, using a
      compensatory display. Simulating a vehicular control task, the direction of
      vehicular motion was shown on the outside visual display in two ways: an explicit
      presentation using a symbol and an implicit presentation, namely, through the
      focus of radial outflow that emerges from optic flow. In addition, the effects of
      the relative strength of congruent vestibular motion cues were investigated. The
      dynamic properties of human visual and vestibular motion perception paths were
      modeled using a control-theoretical approach. As expected, improved tracking
      performance was found for the configurations that explicitly showed the direction
      of self-motion. The human visual time delay increased with approximately 150 ms
      for the optic flow conditions, relative to explicit presentations. Vestibular
      motion, providing higher order information on the direction of self-motion,
      allowed subjects to partially compensate for this visual perception delay,
      improving performance. Parameter estimates of the operator control model show
      that, with vestibular motion, the visual feedback becomes stronger, indicating
      that operators are more confident to act on optic flow information when congruent
      vestibular motion cues are present. 

PMID- 22987526
TI  - Barriers and facilitators to BRCA genetic counseling among at-risk Latinas in New
      York City.
AB  - BACKGROUND: Despite underuse of genetic services for hereditary breast and/or
      ovarian cancer risk among Latinas (including counseling and testing for BRCA
      mutations), there is little known about the barriers and facilitators to BRCA
      genetic counseling among this group. It is imperative to first understand factors
      that may impede Latinas seeking BRCA genetic counseling, as it is considered a
      prerequisite to testing. METHODS: Quantitative telephone interviews (N=120) were
      conducted with at-risk Latinas in New York City to investigate interest,
      barriers, and beliefs about BRCA genetic counseling. Statistical analyses
      examined predictors of intention to undergo BRCA genetic counseling. RESULTS:
      Despite moderate levels of awareness, Latinas held largely positive beliefs,
      attitudes, and knowledge about BRCA genetic counseling. Perceived barriers
      included logistic concerns (e.g., where to go, cost/health insurance coverage),
      emotional concerns (e.g., fear, distress), and competing life concerns (e.g., too
      many other things to worry about, too busy taking care of children or family
      members). Multivariate results showed that the strongest predictor of intention
      to undergo BRCA genetic counseling was competing life concerns; Latinas with more
      competing life concerns were less likely to intend to undergo BRCA genetic
      counseling (p=0.0002). Other significant predictors of intention included
      perceived risk of carrying a BRCA mutation (p=0.01) and referral by their
      physician (p=0.02). CONCLUSION: Educational efforts to promote BRCA genetic
      counseling among at-risk Latinas and increase referrals by their physicians
      should incorporate discussion of perceived barriers to counseling, such as
      competing life concerns that Latinas may need to overcome in order to seek
      genetic counseling.

PMID- 22987530
TI  - SAIL: Summation-bAsed Incremental Learning for Information-Theoretic Text
      Clustering.
AB  - Information-theoretic clustering aims to exploit information-theoretic measures
      as the clustering criteria. A common practice on this topic is the so-called Info
      Kmeans, which performs K-means clustering with KL-divergence as the proximity
      function. While expert efforts on Info-Kmeans have shown promising results, a
      remaining challenge is to deal with high-dimensional sparse data such as text
      corpora. Indeed, it is possible that the centroids contain many zero-value
      features for high-dimensional text vectors, which leads to infinite KL-divergence
      values and creates a dilemma in assigning objects to centroids during the
      iteration process of Info-Kmeans. To meet this challenge, in this paper, we
      propose a Summation-bAsed Incremental Learning (SAIL) algorithm for Info-Kmeans
      clustering. Specifically, by using an equivalent objective function, SAIL
      replaces the computation of KL-divergence by the incremental computation of
      Shannon entropy. This can avoid the zero-feature dilemma caused by the use of KL
      divergence. To improve the clustering quality, we further introduce the variable
      neighborhood search scheme and propose the V-SAIL algorithm, which is then
      accelerated by a multithreaded scheme in PV-SAIL. Our experimental results on
      various real-world text collections have shown that, with SAIL as a booster, the
      clustering performance of Info-Kmeans can be significantly improved. Also, V-SAIL
      and PV-SAIL indeed help improve the clustering quality at a lower cost of
      computation. 

PMID- 22987531
TI  - An Effective Methodology for Solving Matrix Games With Fuzzy Payoffs.
AB  - Of the different types of games, the matrix games with fuzzy payoffs have been
      extensively discussed. Two major kinds of solution methods have been devised. One
      is the defuzzification approach based on ranking functions. Another is the two
      level linear programming method which can obtain membership functions of players'
      fuzzy values (or gain floor and loss ceiling). These methods cannot always ensure
      that players' fuzzy/defuzzified values have a common value. The aim of this paper
      is to develop an effective methodology for solving matrix games with payoffs
      expressed by trapezoidal fuzzy numbers (TrFNs). In this methodology, we introduce
      the concept of Alpha-matrix games and prove that players' fuzzy values are always
      identical, and hereby, any matrix game with payoffs expressed by TrFNs has a
      fuzzy value, which is also a TrFN. The upper and lower bounds of any Alpha-cut of
      the fuzzy value and the players' optimal strategies are easily obtained through
      solving the derived four linear programming problems with the upper and lower
      bounds of Alpha-cuts of the fuzzy payoffs. In particular, the fuzzy value can be
      explicitly estimated through solving the auxiliary linear programming with data
      taken from the 1-cut and 0-cut of the fuzzy payoffs. The proposed method in this
      paper is illustrated with a real example and compared with other methods to show
      validity and applicability. 

PMID- 22987532
TI  - A Nonsymmetric Mixture Model for Unsupervised Image Segmentation.
AB  - Finite mixture models with symmetric distribution have been widely used for many
      computer vision and pattern recognition problems. However, in many applications,
      the distribution of the data has a non-Gaussian and nonsymmetric form. This paper
      presents a new nonsymmetric mixture model for image segmentation. The advantage
      of our method is that it is simple, easy to implement, and intuitively appealing.
      In this paper, each label is modeled with multiple D-dimensional Student's t
      distribution, which is heavily tailed and more robust than Gaussian distribution.
      Expectation-maximization algorithm is adopted to estimate model parameters and to
      maximize the lower bound on the data log-likelihood from observations. Numerical
      experiments on various data types are conducted. The performance of the proposed
      model is compared with that of other mixture models, demonstrating the
      robustness, accuracy, and effectiveness of our method. 

PMID- 22987533
TI  - Response to P. Autier and M. Boniol regarding our article--Relationship between
      sunbed use and melanoma risk in a large case-control study in the United Kingdom.

PMID- 22987536
TI  - High performance photoswitches based on flexible and amorphous D-A polymer
      nanowires.
AB  - A fluorene-based donor-acceptor conjugated polymer is synthesized and the polymer
      nanowires are successfully prepared with high quality and large scale using a
      simple and practical template dipping method. These amorphous polymer nanowires
      are flexible and show excellent photoconductive properties with reliable
      reproducibility. The individual nanowire photoswitches exhibit a responsivity as
      high as 1700 mA W(-1)  and an on/off ratio as high as 2000 under a light
      intensity of 5.76 mW cm(-2)  and a driving voltage of 40 V.

PMID- 22987535
TI  - Bcl-xL protein: predictor of complete tumor response in patients with oral cancer
      treated with curative radiotherapy.
AB  - BACKGROUND: We earlier observed altered expression of p53 and Bcl-xL in oral
      cancer cell lines/tissues and wanted to evaluate these proteins for prediction of
      radiotherapy response and outcome. METHODS: Thirty-nine paraffin-embedded,
      pretreatment oral cancer biopsies were analyzed for protein expression using
      immunohistochemistry and correlated with tumor response to radiotherapy and
      disease-free survival (DFS). RESULT: High p53 (p = .040) was observed in female
      versus male patients. Increased p53 intensity (p = .063) was observed in tobacco
      habitues (chewers +/- smokers) versus patients with no habits. In univariate
      analysis, nodal positivity (p = .044) and favorable/complete tumor response (p =
      .002) exhibited a significant correlation with DFS, whereas tumor response
      emerged as an independent predictor of DFS in multivariate analysis.
      Significantly high Bcl-xL (p = .048) was observed in the unfavorable versus
      favorable responders. CONCLUSION: Our study suggests that Bcl-xL expression along
      with clinical parameters may be useful for identifying patients with oral cancer
      likely to draw maximum benefit from curative radiotherapy.

PMID- 22987537
TI  - Real-time mandibular angle reduction surgical simulation with haptic rendering.
AB  - Mandibular angle reduction is a popular and efficient procedure widely used to
      alter the facial contour. The primary surgical instruments, the reciprocating saw
      and the round burr, employed in the surgery have a common feature: operating at a
      high-speed. Generally, inexperienced surgeons need a long-time practice to learn
      how to minimize the risks caused by the uncontrolled contacts and cutting motions
      in manipulation of instruments with high-speed reciprocation or rotation. A
      virtual reality-based surgical simulator for the mandibular angle reduction was
      designed and implemented on a CUDA-based platform in this paper. High-fidelity
      visual and haptic feedbacks are provided to enhance the perception in a realistic
      virtual surgical environment. The impulse-based haptic models were employed to
      simulate the contact forces and torques on the instruments. It provides
      convincing haptic sensation for surgeons to control the instruments under
      different reciprocation or rotation velocities. The real-time methods for bone
      removal and reconstruction during surgical procedures have been proposed to
      support realistic visual feedbacks. The simulated contact forces were verified by
      comparing against the actual force data measured through the constructed
      mechanical platform. An empirical study based on the patient-specific data was
      conducted to evaluate the ability of the proposed system in training surgeons
      with various experiences. The results confirm the validity of our simulator. 

PMID- 22987538
TI  - Novel fractal feature-based multiclass glaucoma detection and progression
      prediction.
AB  - We investigate the use of fractal analysis (FA) as the basis of a system for
      multiclass prediction of the progression of glaucoma. FA is applied to pseudo two
      dimensional images converted from one-dimensional retinal nerve fiber layer
      (RNFL) data obtained from the eyes of normal subjects, and from subjects with
      progressive and non-progressive glaucoma. FA features are obtained using a box
      counting method and a multi-fractional Brownian motion method that incorporates
      texture and multiresolution analyses. Both features are used for Gaussian kernel
      based multiclass classification. Sensitivity, specificity, and area under
      receiver operating characteristic curve (AUROC) are computed for the FA features
      and for metrics obtained using wavelet-Fourier analysis (WFA) and fast-Fourier
      analysis (FFA). The AUROCs that predict progressors from non-progressors based on
      classifiers trained using a dataset comprised of non-progressors and ocular
      normal subjects are 0.70, 0.71 and 0.82 for WFA, FFA, and FA, respectively. The
      correct multiclass classification rates among progressors, non-progressors, and
      ocular normal subjects are 0.82, 0.86 and 0.88 for WFA, FFA, and FA,
      respectively. Simultaneous multiclass classification among progressors, non
      progressors, and ocular normal subjects has not been previously described. The
      novel FA-based features achieve better performance with fewer features and less
      computational complexity than WFA and FFA. 

PMID- 22987539
TI  - Nitrogen use efficiency in grain production and the estimated nitrogen
      input/output balance in China agriculture.
AB  - BACKGROUND: Understanding the nitrogen (N) use efficiency and N input/output
      balance in the agricultural system is crucial for best management of N
      fertilisers in China. RESULTS: In the last 60 years, N fertiliser consumption
      correlated positively with grain production. During that period the partial
      factor productivity of N (PFPN ) declined greatly from more than 1000 kg grain kg
      1 N in the 1950s to nearly 30 kg grain kg-1 N in 2008. This change in PFPN could
      be largely explained by the increase in N rate. The average agronomic efficiency
      of fertiliser N (AEN ) for rice, wheat and maize during 2000-2010 was 12.6, 8.3
      and 11.5 kg kg-1 respectively, which was similar to that in the early 1980s but
      lower than that in the early 1960s. Estimation based on statistical data showed
      that a total of 49.16 * 106 t of N was input into Chinese agriculture, of which
      chemical N, organic fertiliser N, biological fixed N and other sources accounted
      for 58.2, 24.3, 10.5 and 7.0% respectively. Nitrogen was surplus in all regions,
      the total N surplus being 10.6 * 106 t (60.6 kg ha-1). CONCLUSION: The great
      challenge is to balance the use of current N fertilisers between regions and
      crops to improve N use efficiency while maintaining or increasing crop production
      under the high-intensity agricultural system of China.

PMID- 22987540
TI  - Microextraction by packed sorbent and liquid chromatography-tandem mass
      spectrometry as a tool for quantification of peptides in plasma samples:
      determination of sensory neuron-specific receptors agonist BAM8-22 and antagonist
      BAM22-8 in plasma samples.
AB  - Microextraction by packed sorbent (MEPS) is a miniaturized, solid-phase
      extraction (SPE) technique that works online with gas chromatography (GC) and
      liquid chromatography (LC). Not only is the automation process with MEPS
      advantageous, but the much smaller volumes of the samples, solvents and dead
      space in the system also provide other significant advantages such as the speed
      and the simplicity of the sample preparation process. In this study MEPS has been
      evaluated for quantification of sensory neuron-specific receptors agonist (BAM8
      22). Owing to the instability of BAMs, the focus was on fast extraction and
      determination of the peptide online using LC-MS/MS. Sorbents such as C2, C8 and
      ENV+ (hydroxylated polystyrene-divinylbenzene copolymer) were investigated in the
      present study. MEPS-C8 gave the best results compared with C2 and ENV and it was
      used for the method validation. The calibration curve was obtained within the
      concentration range of 20.0-3045 nmol/L in plasma. The regression correlation
      coefficients for plasma samples were >= 0.99 for all runs (n = 6). The between
      batch accuracy and precision for BAM8-22 ranged from -13 to -2.0% and from 4.0 to
      14%, respectively. Additionally, the accuracy and precision for BAM22-8 ranged
      from -13 to 7.0% and from 3.0 to 12%, respectively. The present method was used
      for pharmacokinetic studies for BAMs in plasma samples.

PMID- 22987541
TI  - Osteopathia striata with cranial sclerosis and developmental delay in a male with
      a mosaic deletion in chromosome region Xq11.2.
AB  - Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused
      by mutations involving WTX (FAM123B), a tumor suppressor protein with dual
      functions. OSCS typically affects females whereas males generally have fetal or
      neonatal lethality. Surviving affected males have characteristic facial
      dysmorphisms, skeletal features such as macrocephaly and short stature,
      neurodevelopmental disabilities and a high prevalence of neuromuscular anomalies.
      On imaging, hemizygous males display marked cranial and peripheral skeletal
      sclerosis without the metaphyseal striations that are seen in women with OSCS.
      Observations of striation in males may be indicative of a somatic mosaic mutation
      in WTX. To date only two cases of surviving males haves been confirmed with
      mosaic point mutations in WTX. We report on the first case of a male with a
      mosaic deletion of the entire WTX gene. We show that a mosaic deletion in a
      hemizygous male patient can cause a mild phenotype of OSCS, including facial and
      skull base bone striations, nasal stenosis, conductive hearing loss, global
      developmental delay, and mild facial dysmorphology without short stature or
      macrocephaly.

PMID- 22987542
TI  - Selectivity for specific cardiovascular effects of vagal nerve stimulation with a
      multi-contact electrode cuff.
AB  - The cardiovascular system can be influenced by electrically stimulating the vagal
      nerve. Selectivity for specific cardiac fibers may be limited when stimulating at
      the cervical level. Our objective was to increase effectiveness and selectivity
      for cardiovascular effects of vagal nerve stimulation by using local bipolar
      stimulation in one nerve cross section using a multi-contact cuff instead of less
      localized stimulation using a tripolar ring electrode. Both types of cuff
      electrodes were compared with respect to their relative effects on R-R interval
      (RRI), P-Q interval (PQI), left ventricular contractility (LVC), and left
      ventricular pressure  (P(LV)) in seven pigs. Stimulation using the optimal
      bipolar configuration on the multi-contact cuff significantly affected RRI, PQI,
      LVC, and  P(LV), whereas stimulation with the ring electrode only significantly
      affected RRI and PQI. The cardiovascular parameters that could be significantly
      influenced varied between the bipolar configurations. These novel findings may be
      relevant for optimizing electrode configurations for clinical cardiac
      applications of vagal nerve stimulation.

PMID- 22987543
TI  - [{Fe(CO)3}4{SnI}6I4]2-: the first bimetallic adamantane-like cluster.
AB  - Show some metal: the first bimetallic adamantane-like cluster,
      [{Fe(CO)(3)}(4){SnI}(6)I(4)](2-), was prepared by an ionic-liquid-based
      synthesis. The valence states of iron and tin were verified based on bond-length
      considerations, FT-IR and (119)Sn Mossbauer spectroscopy, as well as with DFT
      calculations.

PMID- 22987546
TI  - Efficient curing of vinyl carbonates by thiol-ene polymerization.
AB  - Vinyl carbonates have recently been identified as a suitable alternative to
      (meth)acrylates, especially due to the low irritancy and cytotoxicity of these
      monomers. The drawback of some vinyl carbonates containing abstractable hydrogens
      arises through their moderate reactivity compared with acrylates. Within this
      paper, we use the thiol-ene concept to enhance the photoreactivity of vinyl
      carbonates to a large extent to reach the level of those of similar acrylates.
      Mechanical properties of the final thiol-ene polymers were determined by
      nanoindentation. Furthermore, low toxicity of all components was confirmed by
      osteoblast cell culture experiments.

PMID- 22987547
TI  - Large-area, electronically monodisperse, aligned single-walled carbon nanotube
      thin films fabricated by evaporation-driven self-assembly.
AB  - By varying the evaporation conditions and the nanotube and surfactant
      concentrations, large-area, aligned single-walled carbon nanotube (SWCNT) thin
      films are fabricated from electronically monodisperse SWCNT solutions by
      evaporation-driven self-assembly with precise control over the thin film growth
      geometry. Tunability is possible from 0.5 MUm stripes to continuous thin films.
      The resulting SWCNT thin films possess highly anisotropic electrical and optical
      properties that are well suited for transparent conductor applications.

PMID- 22987548
TI  - RE: Relationship between sunbed use and melanoma risk in a large case-control
      study in the United Kingdom.

PMID- 22987549
TI  - Illustrating the machinery of life: viruses.
AB  - Data from electron microscopy, X-ray crystallography, and biophysical analysis
      are used to create illustrations of viruses in their cellular context. This
      report describes the scientific data and artistic methods used to create three
      illustrations: a depiction of the poliovirus lifecycle, budding of influenza
      virus from a cell surface, and a mature HIV particle in blood serum.

PMID- 22987550
TI  - The Bohr effect before Perutz.
AB  - Before the outbreak of World War II, Jeffries Wyman postulated that the Bohr
      effect in hemoglobin demanded the oxygen linked dissociation of the imidazole of
      two histidines of the polypeptide. This proposal emerged from a rigorous analysis
      of the acid-base titration curves of oxy- and deoxy-hemoglobin, at a time when
      the information on the chemistry and structure of the protein was essentially
      nil. The magnetochemical properties of hemoglobin led Linus Pauling to
      hypothesize that the (so called) Bohr histidines were coordinated to the heme
      iron in the fifth and sixth positions; and Wyman shared this opinion. However,
      this structural hypothesis was abandoned in 1951 when J. Wyman and D. W. Allen
      proposed the pK shift of the oxygen linked histidines to be the result of "...a
      change of configuration of the hemoglobin molecule as a whole accompanying
      oxygenation." This shift in paradigm, that was published well before the 3D
      structure of hemoglobin was solved by M.F. Perutz, paved the way to the concept
      of allostery. After 1960 the availability of the crystallographic structure
      opened new horizons to the interpretation of the allosteric properties of
      hemoglobin.

PMID- 22987551
TI  - Engagement of students with lectures in biochemistry and pharmacology.
AB  - Academic staff at universities have become concerned about the decrease in
      student attendance at lectures and the implication of this on student achievement
      and learning. Few studies have measured actual lecture attendance in a coherent
      or comprehensive way. The aim of this study was to measure actual lecture
      attendance of students over two year levels enrolled in two separate science
      disciplines, biochemistry and pharmacology. The study further sought to determine
      the factors that influence lecture attendance. Attendance at lectures in four
      units of study was monitored over a 12-week semester. Attendance at lectures
      decreased over the semester and was lower at early morning lectures (8 A.M.; 9
      A.M.). A questionnaire surveying students about their preparation for lectures,
      their compensation for missed lectures and the factors influencing their
      nonattendance was administered at the end of the semester. Students reported that
      the major factors influencing their attendance at lectures related to timetable
      issues and the quality of lecturing. If students missed lectures, the majority
      read the lecture notes and listened to the online recordings. The availability of
      online recordings of lectures was not a major influence on attendance at
      lectures. In three of the four units studied there was no correlation between
      self-reported lecture attendance and exam performance. The results of the study
      indicate that universities should dedicate more resources to timetabling and to
      supporting staff to improve the quality of their lectures.

PMID- 22987552
TI  - Integration of bioinformatics into an undergraduate biology curriculum and the
      impact on development of mathematical skills.
AB  - The development of fields such as bioinformatics and genomics has created new
      challenges and opportunities for undergraduate biology curricula. Students
      preparing for careers in science, technology, and medicine need more intensive
      study of bioinformatics and more sophisticated training in the mathematics on
      which this field is based. In this study, we deliberately integrated
      bioinformatics instruction at multiple course levels into an existing biology
      curriculum. Students in an introductory biology course, intermediate lab courses,
      and advanced project-oriented courses all participated in new course components
      designed to sequentially introduce bioinformatics skills and knowledge, as well
      as computational approaches that are common to many bioinformatics applications.
      In each course, bioinformatics learning was embedded in an existing disciplinary
      instructional sequence, as opposed to having a single course where all
      bioinformatics learning occurs. We designed direct and indirect assessment tools
      to follow student progress through the course sequence. Our data show significant
      gains in both student confidence and ability in bioinformatics during individual
      courses and as course level increases. Despite evidence of substantial student
      learning in both bioinformatics and mathematics, students were skeptical about
      the link between learning bioinformatics and learning mathematics. While our
      approach resulted in substantial learning gains, student "buy-in" and engagement
      might be better in longer project-based activities that demand application of
      skills to research problems. Nevertheless, in situations where a concentrated
      focus on project-oriented bioinformatics is not possible or desirable, our
      approach of integrating multiple smaller components into an existing curriculum
      provides an alternative.

PMID- 22987553
TI  - Using simple manipulatives to improve student comprehension of a complex
      biological process: protein synthesis.
AB  - Biological systems and living processes involve a complex interplay of
      biochemicals and macromolecular structures that can be challenging for
      undergraduate students to comprehend and, thus, misconceptions abound. Protein
      synthesis, or translation, is an example of a biological process for which
      students often hold many misconceptions. This article describes an exercise that
      was developed to illustrate the process of translation using simple objects to
      represent complex molecules. Animations, 3D physical models, computer
      simulations, laboratory experiments and classroom lectures are also used to
      reinforce the students' understanding of translation, but by focusing on the
      simple manipulatives in this exercise, students are better able to visualize
      concepts that can elude them when using the other methods. The translation
      exercise is described along with suggestions for background material, questions
      used to evaluate student comprehension and tips for using the manipulatives to
      identify common misconceptions.

PMID- 22987554
TI  - Self-regulation: an unexplored learning model in biochemistry and molecular
      biology.

PMID- 22987555
TI  - Improving journal club: increasing student discussion and understanding of
      primary literature in molecular biology through the use of dialectical notes.
AB  - Reading the primary literature in a journal club format is an excellent practice
      where undergraduate students can develop their abilities in experimental data
      analysis and critical thinking, learn about new ideas and methods, and gain a
      foothold in scientific discourse. However, students are not familiar with the
      format, writing style, and depth of knowledge assumed when first reading journal
      articles. This can inhibit class discussion. To alleviate this problem, the
      author has instituted the use of dialectical notes in journal club, so that
      students fully engage the article. This novel use of a strategy borrowed from
      humanities has improved class participation.

PMID- 22987557
TI  - Commentary: the Khan academy and the day-night flipped classroom.

PMID- 22987556
TI  - Problem-solving test: signal transduction in Philadelphia chromosome positive
      leukemia cells.
AB  - Terms to be familiar with before you start to solve the test: reciprocal
      translocation, proto-oncogene, gene expression, c-Abl, tyrosine protein kinases,
      transmembrane protein, G protein, Src protein, malignant transformation,
      transfection, immunoprecipitation, pre-immune serum, [gamma-(32)P]ATP, cAMP, SDS
      polyacrylamide gel electrophoresis, autoradiography, Western blot (immunoblot),
      co-immunoprecipitation, expression vector, cDNA, transient transfection, reporter
      gene, reporter plasmid, promoter, Ras protein, transformed foci, extracellular
      signal-regulated kinase.

PMID- 22987558
TI  - Proteopedia entry: "Tutorial: How we get the oxygen we breathe".

PMID- 22987560
TI  - Evaluation of p16(INK4a)/Ki-67 dual stain in comparison with an mRNA human
      papillomavirus test on liquid-based cytology samples with low-grade squamous
      intraepithelial lesion.
AB  - BACKGROUND: The objective of the current study was to investigate the clinical
      performance of detecting high-grade lesions with the CINtec PLUS p16(INK4a)/Ki-67
      dual stain and the APTIMA human papillomavirus (HPV) Assay in a cohort of women
      with low-grade squamous intraepithelial lesion (LSIL) cytology. The authors also
      assessed the reproducibility of the evaluation of immunocytochemical staining.
      METHODS: The 2 tests were performed on liquid-based residual material from 469
      women with LSILs. The samples had at least 5 years of follow-up and the gold
      standard used was high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+)
      proven on histology. RESULTS: Approximately 69% of all the women included in the
      study had a positive test for HPV mRNA and 56% was positive for the dual stain.
      The 2 tests demonstrated high sensitivities. When examining the specificities,
      the APTIMA HPV Assay performed with significantly lower values than the CINtec
      PLUS test. For patients with CIN2+, the APTIMA HPV Assay had a specificity of
      36.1% versus 51.3% for the CINtec PLUS test, and for women with CIN3+, the
      specificity was 33.8% versus 48.2%, respectively. The difference was even more
      pronounced when analyzing women aged < 30 years separately. The kappa values
      between the 3 observers in scoring the dual stain ranged from 0.43 to 0.49 and
      improved in a second evaluation round to values ranging from 0.50 to 0.66.
      CONCLUSIONS: The CINtec PLUS p16(INK4a)/Ki-67 dual-staining test in LSIL cytology
      samples demonstrated high sensitivity that was similar to that of the APTIMA HPV
      Assay in the detection of underlying high-grade disease but with enhanced
      specificity, especially among women aged < 30 years. The kappa value for the
      evaluation of the CINtec PLUS dual-staining test was moderate but could be
      improved through training.

PMID- 22987561
TI  - Contaminants of emerging concern in municipal wastewater effluents and marine
      receiving water.
AB  - The occurrence and concentrations of contaminants of emerging concern (CECs) were
      investigated in municipal effluents and in marine receiving water. Final effluent
      from four large publicly owned treatment works (POTWs) and seawater collected
      near the respective POTW outfall discharges and a reference station were
      collected quarterly over one year and analyzed for 56 CECs. Several CECs were
      detected in effluents; naproxen, gemfibrozil, atenolol, and tris(1-chloro-2
      propyl)phosphate were the compounds most frequently found and with the highest
      concentrations (>1 ug/L). Gemfibrozil and naproxen had the highest seawater
      concentrations (0.0009 and 0.0007 ug/L) and also were among the most frequently
      detected compounds. Effluent dilution factors ranged from >400 to approximately
      1,000. Fewer CECs were detected and at lower concentrations in seawater collected
      from the reference station than at the outfall sites. Effluent concentrations for
      some CECs (e.g., pharmaceuticals) were inversely related to the degree of
      wastewater treatment. This trend was not found in seawater samples. Few temporal
      differences were observed in effluent or seawater samples. Effluent CEC
      concentrations were lower than those currently known for chronic toxicity
      thresholds. Nevertheless, the evaluation of potential chronic effects for CECs is
      uncertain because aquatic life toxicity thresholds have been developed for only a
      few CECs, and the effluent and seawater samples had compounds, such as
      nonylphenol, known to bioaccumulate in local fish. Additional data are needed to
      better understand the significance of CEC presence and concentrations in marine
      environments.

PMID- 22987562
TI  - Vagal nerve stimulation without dissecting the carotid sheath during
      intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid
      surgery.
AB  - BACKGROUND: Vagal nerve stimulation (VNS) has been recommended as a routine
      procedure during intraoperative neuromonitoring (IONM) of the recurrent laryngeal
      nerve (RLN). However, many surgeons have been discouraged from performing VNS
      because of the need for opening the carotid sheath. The purpose of this study was
      to investigate the feasibility and reliability of VNS without carotid sheath
      dissection. METHODS: Two hundred twenty patients with 376 nerves at risk were
      enrolled in this study. VNS without nerve exposure during IONM was applied by
      simply pressing a ball-tip stimulator on the space between the carotid artery and
      jugular vein. RESULTS: VNS without nerve exposure was feasible in all cases and
      did not result in any morbidity. All VNS signals were successfully obtained
      within 30 minutes of the start of the operation and all showed a clear and
      reliable laryngeal electromyography (EMG) response that was similar to that from
      the conventional method in which nerve exposure for VNS is applied. CONCLUSIONS:
      VNS without dissecting the carotid sheath is feasible and reliable, rendering it
      a simple, safe, and surgeon-friendly procedure during IONM.

PMID- 22987564
TI  - Sonographic diagnosis and monitoring of localized langerhans cell histiocytosis
      of the skull.
AB  - PURPOSE: Langerhans cell histiocytosis (LCH) is an infrequent disorder of unknown
      origin associated with histiocytic proliferation. The bones' involvement
      (including cranial bones) is the most frequent manifestation of pediatric LCH.
      Imaging of skull LCH is based predominantly on conventional radiography, CT,
      scintigraphy, and sometimes MRI. The aim of the study was to investigate the role
      of sonography (US) in the diagnosis and monitoring of bone lesions in children
      with localized LCH of the skull. METHODS: Twenty-seven children (15 boys/12
      girls, mean age 6.1 years) were diagnosed between 1991 and 2005 in the Department
      of Pediatrics at the Medical University of Gdansk, Poland. Fourteen children
      (52%) had localized LCH of the skull. RESULTS: All lesions of the skull visible
      on CT were visualized on US examination. Overall, 30 focal lesions were revealed
      by US. The largest bone lesions were accompanied by changes within the adjacent
      soft tissues. CT revealed 26 lesions, the location and size of which corresponded
      to the lesions seen on US, but soft-tissue changes adjacent to the bony lesions
      were difficult to visualize. CONCLUSIONS: The US appearance of focal LCH lesions
      in cranial bones in children is not pathognomonic, but is characteristic enough
      to suggest an initial diagnosis and to monitor the evolution of lesions during
      treatment. US should be considered an additional diagnostic tool for LCH of the
      skull. Although US of localized LCH cannot replace CT, it could reduce the number
      of follow-up CT examinations.

PMID- 22987566
TI  - Implications of the use of genetic tests in psychiatry, with a focus on major
      depressive disorder: a review.
AB  - Advances in technology have enabled research to link many genetic markers to
      specific disease risk. This has led to the commercialization of genetic tests
      across a wide range of medical disorders. Public interest in one's own future
      health and an increasing desire for autonomy over one's health care have
      facilitated a large and growing market for such genetic tests to be sold direct
      to the consumer (DTC). Amidst a plethora of tests for a broad range of medical
      conditions, DTC genetic tests currently include a number of tests related to risk
      for various psychiatric illnesses including major depressive disorder (MDD),
      bipolar disorder, schizophrenia, and obsessive-compulsive disorder and also for
      prediction of individual response to psychotropic medication. Although a large
      number of studies show that there is strong public interest in genetic
      susceptibility testing for psychiatric disorders, little is known about the
      impact on individuals of receiving the results of genetic tests. Moreover, the
      low predictive power and uncertain clinical validity and utility of DTC genetic
      tests for psychiatric disorders have led to both controversy and difficulties of
      interpretation of results. This review summarizes the rationale for using genetic
      risk tests in psychiatry, as an intervention for protective cognitive and
      behavioral change, and to predict medication response, with a focus on MDD. Since
      genetic risk information has the potential to influence major life-changing
      health decisions, there is an imperative to ensure that there is an appropriate
      evidence base to support the use of such genetic tests.

PMID- 22987565
TI  - Pathogenesis of hypertrophic cardiomyopathy caused by myozenin 2 mutations is
      independent of calcineurin activity.
AB  - AIMS: The role of calcineurin protein phosphatase 2B (PP2B) in the pathogenesis
      of human hypertrophic cardiomyopathy (HCM) remains unsettled. We determined
      potential involvement of calcineurin in the pathogenesis of HCM caused by
      mutations in myozenin 2 (MYOZ2), an inhibitor of calcineurin. METHODS AND
      RESULTS: We generated multiple lines of transgenic mice expressing either Flag
      tagged wild-type (WT) (MYOZ2(WT)) or mutant MYOZ2(S48P) and MYOZ2(I246M),
      identified in families with HCM, in the heart. To mimic the human genotype, we
      generated bigenic mice expressing WT and mutant MYOZ2 in the background of
      hemizygous endogenous MYOZ2 (Myoz2(+/-)). Transgene proteins constituted 15-48%
      of the total MYOZ2 protein in the heart. Mutant MYOZ2 mice showed molecular,
      cellular, and gross cardiac hypertrophy, preserved systolic function, and
      interstitial fibrosis. Immunofluorescence staining showed co-localization of WT
      and mutant MYOZ2 proteins with alpha-actinin at the Z disks. Electron microscopy
      showed disrupted and mal-aligned Z disks in the mutant mice. Cardiac calcineurin
      activity, determined by quantifying Rcan1.4 mRNA and protein levels, luciferase
      activity in triple transgenic Myoz2(+/-):NFATc-Luc:MYOZ2(I246M) and Myoz2(+/
      ):NFATc-Luc:MYOZ2(WT) mice, and NFATc transcriptional activity assay, was
      unchanged in the mutant transgenic mice. However, levels of phospho-ERK1/2 and
      JNK54/46 were altered in the transgenic mice. Likewise, lentiviral-mediated
      expression of the MYOZ2(I246M) did not affect RCAN1.4 and calcineurin (PPP3CB)
      protein levels. CONCLUSIONS: Thus, the cardiac phenotype in HCM caused by MYOZ2
      mutations might be independent of calcineurin activity in the heart. Z disk
      abnormalities might provide the stimulus for the induction of cardiac hypertrophy
      caused by MYOZ2 mutations.

PMID- 22987567
TI  - Integrated wildfire risk assessment: framework development and application on the
      Lewis and Clark National Forest in Montana, USA.
AB  - The financial, socioeconomic, and ecological impacts of wildfire continue to
      challenge federal land management agencies in the United States. In recent years,
      policymakers and managers have increasingly turned to the field of risk analysis
      to better manage wildfires and to mitigate losses to highly valued resources and
      assets (HVRAs). Assessing wildfire risk entails the interaction of multiple
      components, including integrating wildfire simulation outputs with geospatial
      identification of HVRAs and the characterization of fire effects to HVRAs. We
      present an integrated and systematic risk assessment framework that entails 3
      primary analytical components: 1) stochastic wildfire simulation and burn
      probability modeling to characterize wildfire hazard, 2) expert-based modeling to
      characterize fire effects, and 3) multicriteria decision analysis to characterize
      preference structures across at-risk HVRAs. We demonstrate application of this
      framework for a wildfire risk assessment performed on the Little Belts Assessment
      Area within the Lewis and Clark National Forest in Montana, United States. We
      devote particular attention to our approach to eliciting and encapsulating expert
      judgment, in which we: 1) adhered to a structured process for using expert
      judgment in ecological risk assessment, 2) used as our expert base local resource
      scientists and fire/fuels specialists who have a direct connection to the
      specific landscape and HVRAs in question, and 3) introduced multivariate response
      functions to characterize fire effects to HVRAs that consider biophysical
      variables beyond fire behavior. We anticipate that this work will further the
      state of wildfire risk science and will lead to additional application of risk
      assessment to inform land management planning.

PMID- 22987568
TI  - Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid
      dysplasia.
AB  - Progressive pseudorheumatoid dysplasia (PPD) is a progressive skeletal syndrome
      characterized by stiffness, swelling and pain in multiple joints with associated
      osteoporosis in affected patients. Radiographically, the predominant features
      resemble a spondyloepiphyseal dysplasia. Mutations in the WISP3 gene are known to
      cause this autosomal recessive condition. To date, only a limited number of
      studies have looked into the spectrum of mutations causing PPD. We report on
      clinical features and WISP3 mutations in a large series of Indian patients with
      this rare skeletal dysplasia. Families with at least one member showing clinical
      and radiologic features of PPD were recruited for the study. Symptoms, signs and
      radiographic findings were documented in 35 patients from 25 unrelated families.
      Swelling of small joints of hands and contractures are the most common presenting
      features. Mutation analysis was carried out by bidirectional sequencing of the
      WISP3 gene in all 35 patients. We summarize the clinical features of 35 patients
      with PPD and report on 11 different homozygous mutations and one instance of
      compound heterozygosity. Eight (c.233G>A, c.340T>C, c.348C>A, c.433T>C, c.682T>C,
      c.802T>G, c.947_951delAATTT, and c.1010G>A) are novel mutations and three
      (c.156C>A, c.248G>A, and c.739_740delTG) have been reported previously. One
      missense mutation (c.1010G>A; p.Cys337Tyr) appears to be the most common in our
      population being seen in 10 unrelated families. This is the largest cohort of
      patients with PPD in the literature and the first report from India on mutation
      analysis of WISP3. We also review all the mutations reported in WISP3 till date.

PMID- 22987569
TI  - Anatomical evaluation and stress distribution of intact canine femur.
AB  - BACKGROUND: In the biomedical field, three-dimensional (3D) modeling and analysis
      of bones and tissues has steadily gained in importance. The aim of this study was
      to produce more accurate 3D models of the canine femur derived from computed
      tomography (CT) data by using several modeling software programs and two
      different methods. METHOD: The accuracy of the analysis depends on the modeling
      process and the right boundary conditions. Solidworks, Rapidform, Inventor, and
      3DsMax software programs were used to create 3D models. Data derived from CT were
      converted into 3D models using two different methods: in the first, 3D models
      were generated using boundary lines, while in the second, 3D models were
      generated using point clouds. RESULTS: Stress analyses in the models were made by
      ANSYS v12, also considering any muscle forces acting on the canine femur. When
      stress values and statistical values were taken into consideration, more accurate
      models were obtained with the point cloud method. CONCLUSION: It was found that
      the maximum von Mises stress on the canine femur shaft was 34.8 MPa. Stress and
      accuracy values were obtained from the model formed using the Rapidform software.
      The values obtained were similar to those in other studies in the literature.

PMID- 22987570
TI  - Broadband and omnidirectional, nearly zero reflective photovoltaic glass.
AB  - A novel two-step etching approach is used to modify the surface layer of
      photovoltaic glasses, leading to a porous surface layer with a graded refractive
      index, and nearly 100% transmittance over a broad range of wavelengths, from
      ultraviolet to near infrared.

PMID- 22987571
TI  - Single-step modified QuEChERS for determination of chlorothalonil in shallot
      (Allium ascalonicum) using GC-MUECD and confirmation via mass spectrometry.
AB  - A single extraction method was developed for chlorothalonil in shallot using gas
      chromatography with an electron capture detector (GC-MUECD). Samples were
      extracted with single-step modified quick, easy, cheap, effective, rugged, and
      safe (QuEChERS) method using ethyl acetate as an extraction solvent. Significant
      matrix effects were observed, and the calibration curve was constructed from the
      matrix. The linearity of the analytical response across the studied range of
      concentrations (0.01-1.00 mg/L) was excellent, obtaining a correlation
      coefficient (r(2) ) of 0.996. >0.996. Recovery studies were carried out on spiked
      shallot blank samples, at two concentration levels (0.4 and 2.0 mg/kg) with three
      replicates performed at each level. Mean recoveries of 97.2-104.9% with RSDs of
      1.3-2.7% were obtained. The method is demonstrated to be suitable for the
      determination of chlorothalonil in shallot. The dissipation rates of
      chlorothalonil were described using first-order kinetics, and its half-life was
      2.8 days. Based on the dissipation pattern of the pesticide residues, the pre
      harvest residue limit (PHRL) was also calculated. Residues were confirmed via
      mass spectrometry.

PMID- 22987572
TI  - Influence of high-dose lipid lowering treatment compared to low-dose lipid
      lowering treatment on plaque composition assessed by intravascular ultrasound
      virtual histology in patients with ST-segment elevation acute myocardial
      infarction: the VIRHISTAMI trial.
AB  - AIMS: The aim of this study was to evaluate the effect of low-dose versus high
      dose rosuvastatin therapy on the necrotic core (NC) content in coronary plaques
      of angiographic non-significant lesions as assessed by intravascular ultrasound -
      virtual histology. METHODS AND RESULTS: Eighty-seven statin-naive patients with
      ST-segment elevation myocardial infarction (STEMI) were randomised to 5 mg or 40
      mg rosuvastatin. The volume of each plaque component (necrotic core, fibrous
      tissue, fibro-fatty, and dense calcium) was assessed at baseline and after 12
      months of follow-up. Baseline low-density lipoprotein (LDL) cholesterol level was
      reduced by 31.8% in the low-dose group (from 3.1+/-0.7 mmol/l to 2.0+/-0.4
      mmol/l, p<0.001) vs. 49.0% in the high-dose group (from 3.1+/-1.0 mmol/l to 1.6+/
      0.7 mmol/l, p<0.001) (p=0.001 between groups). The plaque component necrotic core
      was reduced by 7.6% in the low-dose group (44.6+/-38.2 mm3 vs. 41.2+/-40.3 mm3,
      p=0.29) compared to 14.2% in the high-dose group (47.4+/-38.2 mm3 vs. 40.7+/-34.4
      mm3, p=0.003) (p=0.38 between groups). CONCLUSIONS: In statin-naive patients with
      STEMI, rosuvastatin therapy for 12 months resulted in significant reduction in
      LDL-cholesterol; however, a significant decrease in necrotic core volume was only
      seen in the high-dose group.

PMID- 22987573
TI  - Prognostic value of vascular endothelial growth factor in patients with head and
      neck cancer: A meta-analysis.
AB  - BACKGROUND: The correlation between vascular endothelial growth factor (VEGF)
      overexpression and the clinical outcome of head and neck cancer remains
      inconclusive. This meta-analysis aimed to evaluate the prognostic value of VEGF
      in patients with head and neck cancer. METHODS: We searched Ovid MEDLINE, EMBASE
      and 2 Chinese science databases in order to enroll all eligible articles. Forty
      seven studies were included in this meta-analysis. All results were evaluated by
      the random-effects model. RESULTS: VEGF overexpression is significantly
      associated with worse overall survival (OS; hazard ratio [HR], 1.89; 95%
      confidence interval [CI], 1.61-2.22) and progression-free survival (PFS; HR,
      1.68; 95% CI, 1.33-2.12). Subgroup analysis reveals that VEGF overexpression is a
      significant poor predictor for nasopharyngeal cancer (HR, 1.66; 95% CI, 1.30
      2.12) and salivary gland cancer (HR, 3.32; 95% CI, 1.61-6.84). CONCLUSION: Our
      meta-analysis supports that VEGF overexpression is an available poor predictor
      for patients with head and neck cancer.

PMID- 22987574
TI  - Alcohol consumption and major depression in the general population: the critical
      importance of dependence.
AB  - BACKGROUND: Substance use disorders and major depressive episodes (MDEs) often co
      occur. Alcohol consumption may contribute to the aetiology of depressive episodes
      and/or vice versa. In Canada, the National Population Health Survey (NPHS)
      evaluated several aspects of alcohol use and MDE in a large population cohort
      over 12 years of follow-up. We evaluated the incidence of MDE in relation to
      different patterns of alcohol use, and examined the incidence of alcohol misuse
      in respondents with and without MDE. METHODS: The NPHS is a longitudinal study
      that began data collection in 1994 and whose cohort has been followed with
      biannual interviews. These interviews assess MDE using the Composite
      International Diagnostic Interview Short Form for Major Depression (CIDI-SFMD).
      Another CIDI-SF module assessed alcohol dependence during two interviews. Any
      alcohol consumption, exceeding moderate drinking guidelines and binge drinking
      were also assessed. We used logistic regression and proportional hazards models
      to assess longitudinal relationships between these variables RESULTS: Respondents
      with alcohol dependence were at higher risk of MDE, but any alcohol consumption,
      exceeding guidelines for moderate drinking and binge drinking were not.
      Respondents with MDE showed no increase of alcohol consumption, but the risk of
      alcohol dependence was elevated in depressed men. CONCLUSION: Of direct clinical
      significance is the bidirectional relationship between alcohol dependence and
      MDE. Associations between alcohol consumption and MDE were not observed except
      when dependence was indicated. Alcohol dependence increased the risk of MDE, and
      MDE increased the risk of alcohol dependence, but only in men.

PMID- 22987576
TI  - Clouded by terminology: Edouard-Gerard Balbiani and the mitochondrial cloud.

PMID- 22987578
TI  - Nonparametric receiver operating characteristic-based evaluation for survival
      outcomes.
AB  - For censored survival outcomes, it can be of great interest to evaluate the
      predictive power of individual markers or their functions. Compared with
      alternative evaluation approaches, approaches based on the time-dependent
      receiver operating characteristics (ROC) rely on much weaker assumptions, can be
      more robust, and hence are preferred. In this article, we examine evaluation of
      markers' predictive power using the time-dependent ROC curve and a concordance
      measure that can be viewed as a weighted area under the time-dependent area under
      the ROC curve profile. This study significantly advances from existing time
      dependent ROC studies by developing nonparametric estimators of the summary
      indexes and, more importantly, rigorously establishing their asymptotic
      properties. It reinforces the statistical foundation of the time-dependent ROC
      based evaluation approaches for censored survival outcomes. Numerical studies,
      including simulations and application to an HIV clinical trial, demonstrate the
      satisfactory finite-sample performance of the proposed approaches.

PMID- 22987579
TI  - Kaposi's sarcoma-derived cell line SLK is not of endothelial origin, but is a
      contaminant from a known renal carcinoma cell line.
AB  - Kaposi's sarcoma (KS) is an endothelial cell-derived tumor. Investigations of the
      molecular mechanisms of KS pathogenesis and the identification of drugs for
      treatment of KS depend critically on valid cell-culture models. Two major
      immortalized cell lines are available for KS research. Recently, the KS cell line
      KS Y-1 has been shown to be cross-contaminated with the T24 urinary bladder
      cancer cell line (ATCC HTB-4). Here, we show by short tandem repeat profiling
      that the second KS cell line, SLK, is indistinguishable from the clear-cell renal
      cell carcinoma cell line Caki-1. Immunocytochemical detection of cytokeratin
      expression confirmed the epithelial-cell origin of SLK cells. Our findings
      indicate that SLK cells are not of endothelial origin and should not be used in
      future studies as a model for KS-derived endothelial tumor cells. We suggest that
      in the future, more attention needs to be paid to the authenticity of cells in
      lines derived from human tissues.

PMID- 22987580
TI  - Projected Hg dietary exposure of 3 bird species nesting on a contaminated
      floodplain (South River, Virginia, USA).
AB  - Dietary Hg exposure was modeled for Carolina wren (Thryothorus ludovicianus),
      Eastern song sparrow (Melospiza melodia), and Eastern screech owl (Otus asio)
      nesting on the contaminated South River floodplain (Virginia, USA).
      Parameterization of Monte-Carlo models required formal expert elicitation to
      define bird body weight and feeding ecology characteristics because specific
      information was either unavailable in the published literature or too difficult
      to collect reliably by field survey. Mercury concentrations and weights for
      candidate food items were obtained directly by field survey. Simulations
      predicted the probability that an adult bird during breeding season would ingest
      specific amounts of Hg during daily foraging and the probability that the average
      Hg ingestion rate for the breeding season of an adult bird would exceed published
      rates reported to cause harm to other birds (>100 ng total Hg/g body weight per
      day). Despite the extensive floodplain contamination, the probabilities that
      these species' average ingestion rates exceeded the threshold value were all
      <0.01. Sensitivity analysis indicated that overall food ingestion rate was the
      most important factor determining projected Hg ingestion rates. Expert
      elicitation was useful in providing sufficiently reliable information for Monte
      Carlo simulation.

PMID- 22987581
TI  - Influence of carbon and lipid sources on variation of mercury and other trace
      elements in polar bears (Ursus maritimus).
AB  - In the present study, the authors investigated the influence of carbon and lipid
      sources on regional differences in liver trace element (As, Cd, Cu, total Hg, Mn,
      Pb, Rb, Se, and Zn) concentrations measured in polar bears (Ursus maritimus) (n =
      121) from 10 Alaskan, Canadian Arctic, and East Greenland subpopulations. Carbon
      and lipid sources were assessed using delta(13) C in muscle tissue and fatty acid
      (FA) profiles in subcutaneous adipose tissue as chemical tracers. A negative
      relationship between total Hg and delta(13) C suggested that polar bears feeding
      in areas with higher riverine inputs of terrestrial carbon accumulate more Hg
      than bears feeding in areas with lower freshwater input. Mercury concentrations
      were also positively related to the FA 20:1n-9, which is biosynthesized in large
      amounts in Calanus copepods. This result raises the hypothesis that Calanus
      glacialis are an important link in the uptake of Hg in the marine food web and
      ultimately in polar bears. Unadjusted total Hg, Se, and As concentrations showed
      greater geographical variation among polar bear subpopulations compared with
      concentrations adjusted for carbon and lipid sources. The Hg concentrations
      adjusted for carbon and lipid sources in Bering-Chukchi Sea polar bear liver
      tissue remained the lowest among subpopulations. Based on these findings, the
      authors suggest that carbon and lipid sources for polar bears should be taken
      into account when one is assessing spatial and temporal trends of long-range
      transported trace elements.

PMID- 22987582
TI  - Behavior and toxicity of graphene and its functionalized derivatives in
      biological systems.
AB  - Graphene, as a class of 2D carbon nanomaterial, has attracted tremendous interest
      in different areas in recent years including biomedicine. The toxicity and
      behavior of graphene in biological systems are thus important fundamental issues
      that require significant attention. In this article, the toxicity of graphene is
      reviewed by describing the behavior of graphene and its derivatives in
      microorganisms, cells, and animals. Despite certain inconsistencies in several
      detailed experimental results and hypotheses of toxicity mechanisms, results from
      numerous reports all agree that the physicochemical properties such as surface
      functional groups, charges, coatings, sizes, and structural defects of graphene
      may affect its in vitro/in vivo behavior as well as its toxicity in biological
      systems. It is hoped that this review article will provide an overview
      understanding of the impacts, behavior, and toxicology of graphene and its
      derivatives in various biological systems.

PMID- 22987583
TI  - Photoswitchable supramolecular catalysis by interparticle host-guest competitive
      binding.
AB  - On and off: ester hydrolysis catalyzed by a Zn(II) -coordinated beta-cyclodextrin
      dimer can be switched on and off using light in the presence of gold
      nanoparticles with azobenzene units attached to their surfaces. Under visible
      light, the azobenzene units are trans and bind tightly to the dimer, thus leading
      to reduced catalysis. Under UV light, the azobenzene units are cis and bind
      loosely to the dimer, thus allowing substrates to bind and hydrolysis to occur.

PMID- 22987584
TI  - Agenesis of a submandibular gland with compensatory pseudotumoral hypertrophy of
      the contralateral gland: sonographic findings.
AB  - Agenesis of a submandibular gland with compensatory hypertrophy of the
      contralateral gland is an extremely rare disorder. Most reported cases of
      unilateral submandibular agenesis have been asymptomatic without any associated
      facial anomalies. We report a case of submandibular gland hypertrophy mimicking a
      mass that was detected incidentally. The absence of the contralateral
      submandibular gland and associated contralateral sublingual gland hypertrophy was
      confirmed by typical imaging findings.

PMID- 22987585
TI  - Glycine betaine: a widely reported osmolyte induces differential and selective
      conformational stability and enhances aggregation in some proteins in the
      presence of surfactants.
AB  - In this study, we extensively report the effect of glycine betaine during the
      refolding of partially folded bovine alpha-lactalbumin (alpha-LA) in presence of
      hexadecyl trimethyl ammonium bromide (HTAB), and Ribonuclease A (RNAse A) in
      presence of sodium dodecyl sulfate (SDS) by different complementary biophysical,
      light scattering, and microscopic techniques. Though a substantial
      refolding/compaction was observed in both the studied proteins, the fluorescence
      studies contradicted the finding obtained from circular dichroism spectroscopy
      (CD) in case of alpha-LA. CD stopped flow showed extensive presence of
      intermediates during the refolding of proteins which could potentially lead to
      aggregation. The aggregates as observed in dynamic light scattering (DLS), in
      alpha-LA were massive as compared to RNAse A and was directly proportional to
      betaine concentration. The zeta potential confirmed that the aggregates are a
      direct manifestation of strong aggregating and/or immense preferential excluding
      tendency of GB and not because of charge neutralization; however a possible role
      of conformational change as observed in FTIR spectroscopy cannot be completely
      ruled out. In contrary though RNAse A showed a substantial refolding, the final
      state of the folded protein was significantly different from the native state.
      These findings for alpha-LA and RNAse A were further supported by electron
      microscopic and thermodynamic studies. We thus propose that betaine has a strong
      macromolecular excluding tendency, primarily directed to shield the hydrophobic
      exposure either by refolding or aggregation, and depending on the hydrophobicity
      of the proteins, the functional restoration of the protein is manifested.

PMID- 22987586
TI  - A short GC-rich palindrome of human mannose receptor gene coding region displays
      a conformational switch.
AB  - Conformational switching in DNA is fundamental to biological processes. The
      structural status of a palindromic GC-rich dodecamer DNA sequence, integral part
      of human MRC2 coding region, and a related sequence of opposite polarity from
      human FDX1 gene were characterized and compared. UV-melting, circular dichroism,
      and gel electrophoresis experiments demonstrated the formation of intermolecular
      structures. Although stability and molecularity of both the oligomeric structures
      were found to be almost identical, their secondary structures differed remarkably
      as A1 MRC2 sequence showed A-like and B-like DNA conformation, whereas the A2
      FDX1 sequence exhibited only the A-like signatures. The study is relevant for
      understanding structural polymorphism at genomic locations depending on DNA
      sequence and solution environment.

PMID- 22987587
TI  - Unexpected high pressure effects on the structural properties of condensed whey
      protein systems.
AB  - We show that application of high hydrostatic pressure (600 MPa for 15 min) on
      condensed whey protein (WP) systems (e.g., 80% w/w solids content) results in
      unexpected structure-function behavior when compared with conventional thermal
      treatment. Unraveling the relaxation properties in first-order thermodynamic
      transitions, the manifestation of glass transition phenomena and the preservation
      of native conformation in condensed preparations were recorded using small
      deformation dynamic oscillation in shear, modulated differential scanning
      calorimetry, and infrared spectroscopy. Informed temperature application results
      in the formation of continuous networks at the denaturation temperature, which
      undergo vitrification at subzero temperatures. In contrast, high-pressure-treated
      WPs resist physicochemical denaturation, hence preserving the native conformation
      of secondary and tertiary structures. This was rationalized on the basis of a
      critical concentration threshold where transfer of water molecules to nonpolar
      residues in the protein interior is minimized because of low moisture content and
      restricted molecular mobility. The physical state and morphology of these high
      solid preparations were further examined by the combined framework of reduced
      variables and Williams, Landel, and Ferry equation/free volume theory.
      Theoretical treatment of experimental observations unveils the dynamic range of
      the mechanical manifestation of the glass transition region in samples subjected
      to heat or pressure. In addition to preserving native conformation, WPs subjected
      to high pressure form glassy systems at parity with the structural functionality
      of the thermally treated counterparts.

PMID- 22987588
TI  - Analysis of mixed DNA-bisnaphthalimide interactions involving groove association
      and intercalation with surface-based and solution methodologies.
AB  - The bisnaphthalimide cytotoxic agent elinafide exhibits a mixed DNA binding mode
      including groove-association and intercalation. We have compared the interaction
      of elinafide and two bisnaphthalimide analogues with various natural and modified
      DNA sequences using solution NMR and UV-melting methods and surface plasmon
      resonance (SPR) experiments at different pH conditions. The combined data
      obtained with these techniques established a high-affinity binding mode
      comprising intercalation and strong electrostatic contacts with guanine bases in
      the major groove, and a weaker interaction with A.T pairs likely involving groove
      association. However, the SPR binding constants and the NMR and UV-melting
      binding parameters responded differently to variations in DNA bases and ligand
      intercalating moieties. The rates and equilibrium constants determined by SPR
      clearly responded to changes in pH and DNA groove composition, but were rather
      insensitive to alterations in drug rings and DNA bases affecting the
      intercalation process. Conversely, the intermolecular stacking interactions
      detected by NMR and the ligand-induced thermal stabilizations measured by UV
      depended on both sets of factors and were controlled by the sequence-dependent
      properties of the DNA helices, indicating that these data were modulated by
      naphthalimide stacking in addition to groove association. A two-step binding
      process where a groove-bound state is required prior to intercalation is proposed
      as an explanation for these observations. These findings may be useful for
      studying other classes of DNA- and RNA-binding drugs, which frequently combine
      groove-binding and stacking moieties.

PMID- 22987589
TI  - Variable chain conformations of renatured beta-glucan in dimethylsulfoxide/water
      mixture.
AB  - We have firstly demonstrated the renaturation process of dissociated single
      chains of lentinan (s-LNT) and the variable conformations of the renatured LNT (r
      LNT). The results from ultrasensitive differential scanning calorimetry and
      circular dichroism revealed that the variable structures including perfect triple
      helix, defective triple helix containing duplex segment, and single chains
      occurred in the renaturation of s-LNT, depending on the renaturation time,
      solvent composition, molecular weight, and the mode of renaturation. When water
      was added into s-LNT/dimethylsulfoxide (DMSO) to reach 95% (v/v), the classic low
      temperature intra-triple-helical conformational transition at ~10( degrees ) C
      (T(1)) appeared within 4 h, indicative of a rapid reconstruction of triple
      helical structure. Besides, one newly endothermic peak at ~43( degrees ) C (T(2))
      simultaneously occurred, which was first ascribed to the melting of duplex
      segment in the imperfect triplex. The duplex stretches disappeared when DMSO
      reached 50%, in which single chains coexisted with triplex. Moreover, the duplex
      segment disappeared by slowly dropping water into s-LNT/DMSO. This work suggested
      that the structure of r-LNT could be controllable, and provided important
      information for their successful development and application in polymer and life
      science.

PMID- 22987590
TI  - Molecular dynamics studies of the antimicrobial peptides piscidin 1 and its
      mutants with a DOPC lipid bilayer.
AB  - Piscidin 1 (Pis-1) has a high broad-spectrum activity against bacteria, fungi,
      and viruses but it also has a moderate hemolytic activities. To improve the
      antibacterial activity and to reduce toxicity, mutants Pis-1AA (G8A/G13A double
      mutant) and Pis-1PG (G8P mutant) have been designed based on the crystal
      structure of Pis-1. Eighteen independent molecular dynamics (MD) simulations of
      Pis-1 and its mutants with membranes are conducted in this article. Furthermore,
      60 independent MD simulations of three peptides in water box have also been
      discussed for comparison. The results indicate that the unfolding process starts
      at the middle of the peptide. Pis-1 disrupts easily in the region of Val10-Lys14.
      Pis-1PG has a flexible N-terminal region, and the interaction between N-terminal
      and C-terminal is very weak. Pis-1AA has the most stable helical structure. In
      addition, percentage of native contacts and hydrogen bonds analysis are also
      performed. Lipid-peptide interaction analysis suggests that Pis-1 and Pis-1AA has
      a stronger interaction with the zwitterionic dioleoylphosphatidylcholine (DOPC)
      lipid bilayer than Pis-1PG. When compared with the results of peptide with
      membrane, peptides are unstable and unfolding quickly in water solution. Our
      results are applicable in examining diversities on hemolytic, antibacterial, and
      selectivity of antimicrobial peptides.

PMID- 22987591
TI  - Solvent-dependent conformation of a regioselective amylose carbamate: amylose-2
      acetyl-3,6-bis(phenylcarbamate).
AB  - Six amylose-2-acetyl-3,6-bis(phenylcarbamate) (AAPC) samples ranging in weight
      average molar mass M(w) from 1.8 * 10(4) g mol(-1) to 1.1 * 10(6) g mol(-1) have
      been prepared from enzymatically synthesized amylose samples. Static light
      scattering, small-angle X-ray scattering, sedimentation equilibrium, and
      viscosity measurements were made for the samples in 1,4-dioxane (DIOX), 2
      ethoxyethanol (2EE), and 2-butanone (MEK) all at 25 degrees C to determine
      particle scattering functions, z-average radii of gyration, intrinsic
      viscosities, as well as M(w). The data were analyzed in terms of the wormlike
      cylinder model mainly to yield the helix pitch per residue h and the Kuhn segment
      length lambda(-1), which corresponds to twice of the persistence length. The
      latter parameters (lambda(-1)) in 2EE (11 nm) and MEK (12 nm) are quite smaller
      than those for amylose tris(phenylcarbamate) (ATPC) in the same solvent (16 nm in
      2EE and 18 nm in MEK) whereas those for AAPC (21 nm) and ATPC (22 nm) in DIOX are
      essentially the same as each other. This indicates that the chain stiffness of
      AAPC is more strongly influenced by the solvents since the number of
      intramolecular H-bonds of AAPC is more changeable than that for ATPC.

PMID- 22987592
TI  - Computationally designed beta-turn foldamers of gamma-peptides based on 2
      (aminomethyl)cyclohexanecarboxylic acid.
AB  - The gamma-peptide beta-turn structures have been designed computationally by the
      combination of chirospecific gamma(2),(3)-residues of 2
      (aminomethyl)cyclohexanecarboxylic acid (gammaAmc(6)) with a cyclohexyl
      constraint on the C(alpha) -C(beta) bond using density functional methods in
      water. The chirospecific gammaAmc(6) dipeptide with the (2S,3S)-(2R,3R)
      configurations forms a stable turn structure in water, resembling a type II' turn
      of alpha-peptides, which can be used as a beta-turn motif in beta-hairpins of Ala
      based alpha-peptides. The gammaAmc(6) dipeptide with homochiral (2S,3S)-(2S,3S)
      configurations but different cyclohexyl puckerings shows the capability to be
      incorporated into one of two beta-turn motifs of gramicidin S. The overall
      structure of this gramicidin S analogue is quite similar to the native gramicidin
      S with the same patterns and geometries of hydrogen bonds. Our calculated results
      and the recently observed results may imply the wider applicability of
      chirospecific gamma-peptides with a cyclohexyl constraint on the backbone to form
      various peptide foldamers.

PMID- 22987595
TI  - Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and
      euploids individuals to atrioventricular septal defect.
AB  - To explore the role of CRELD1 variants on congenital heart defects, we sequenced
      the entire reading frame of CRELD1 in the samples from Kolkata and adjoining
      areas. Nearly, 400 participants were included in the genetic association study
      and they were stratified as Down syndrome (DS) with atrioventricular septal
      defect (AVSD), DS without AVSD, euploid with AVSD, and euploid without AVSD. A
      significant association was found between AVSD and three polymorphisms, namely
      rs9878047 (c.1049-129T > C), rs3774207 (c.1119C > T), and rs73118372 (c.1136T >
      C) among the Down syndrome and euploid individuals. The polymorphism rs73118372,
      involves a transition (c.1136T > C) that leads to change in amino acid methionine
      to threonine which alters protein secondary structure as confirmed by the
      bioinformatics software SOPMA. In addition, two haplotypes, C-T-C and C-T-T, in
      the order of loci rs9878047-rs3774207-rs73118372 were associated with incidence
      of AVSD among euploid and Down syndrome, with a slightly higher odds ratio in the
      later group. We hypothesize that these haplotypes increase the risk of AVSD, and
      the susceptibility is exacerbated in DS, possibly due to the trisomy 21 genetic
      background. Moreover, we report for the first time on an interaction between the
      mutant alleles of rs3774207 and rs73118372 which could disrupt the delicate
      balance between different CRELD1 isoforms.

PMID- 22987593
TI  - Fabrication of gelatin nanofibrous scaffolds using ethanol/phosphate buffer
      saline as a benign solvent.
AB  - Electrospinning of natural polymer nanofibers useful for biomedical applications
      often requires the use of cytotoxic organic solvents. In this study, gelatin
      nanofibers are electrospun from phosphate buffer saline/ethanol binary mixtures
      as a benign solvent at ambient temperature. The influences of ionic strength,
      ethanol concentration, and gelatin concentration on the electrospinnability of
      gelatin solutions and the fiber microarchitectures are analyzed. The electrospun
      scaffolds retain their morphologies during vapor-phase crosslinking with
      glutaraldehyde in ethanol and the subsequent removal of salts contained in the
      nanofibers via water rinsing. When fully hydrated, the mechanically
      preconditioned scaffolds display a Young's modulus of 25.5 +/- 5.3 kPa, tensile
      strength of 55.5 +/- 13.9 kPa, deformability of 160 +/- 15%, and resilience of
      89.9 +/- 1.8%. When cultured on the gelatin scaffolds, 3T3 fibroblasts displayed
      spindle-like morphology, similar to the cell's normal morphology in a 3D
      extracellular matrix.

PMID- 22987596
TI  - Developmental iodine deficiency delays the maturation of newborn granule neurons
      associated with downregulation of p35 in postnatal rat hippocampus.
AB  - We evaluated the role of p35 in the maturation of hippocampal granule neurons in
      offspring caused by developmental iodine deficiency. Two developmental rat models
      were established with either an iodine-deficient diet, or propylthiouracil
      adulterated water (5 ppm) to impair thyroid function, in pregnant rats from
      gestational day 6 until postnatal day 28. The protein levels of p35, cyclin
      dependent kinase 5, beta-catenin, and N-cadherin were assessed on postnatal day
      14, 21, and 28. Dendritic morphogenesis of newborn granule neurons in dentate
      gyrus was examined. Developmental hypothyroidism induced by iodine deficiency and
      PTU treatment delayed the maturation of hippocampal granule neurons in the
      offspring and decreased the percentage of Dcx-positive neurons that expressed
      beta-catenin on postnatal day 21 and 28. In addition, downregulation of p35 was
      observed in dentate gyrus of hypothyroid groups. Developmental hypothyroidism
      induced by iodine deficiency and PTU treatment could delay the maturation of
      newborn granule neurons in dentate gyrus, and this deficit may be attributed to
      the downregulation of p35.

PMID- 22987597
TI  - Hypopharyngeal paraganglioma with a paraneoplastic neurologic syndrome: a case
      report.
AB  - BACKGROUND: We report an extremely rare case of hypopharyngeal paraganglioma that
      was accompanied by a paraneoplastic neurologic syndrome (PNS). METHODS: The
      clinical, radiological, and histopathologic findings of the patient are
      presented. RESULTS: A 49-year-old woman presented with a history of progressive
      asthenia of the lower extremities persisting for 2 months. She also experienced
      numbness and sensory disturbance of the left lower limbs, 2 epileptic seizures,
      and constipation during the period. Clinical and radiological evaluations
      suggested the diagnosis of encephalomyelitis in combination with a left
      hypopharyngeal mass lesion. The patient underwent surgical excision of the
      lesion, which subsequently resolved her symptoms. Postoperative pathology was
      consistent with a paraganglioma. There was no evidence of local recurrence or
      distant metastasis of the tumor on recent follow-up. CONCLUSIONS: To the best of
      our knowledge, our patient represents the third reported case of hypopharyngeal
      paraganglioma, and the only one to have a paraneoplastic syndrome.

PMID- 22987598
TI  - Proteomic analysis of mitochondria from infantile hemangioma endothelial cells
      treated with sodium morrhuate and its liposomal formulation.
AB  - Hemangioma is the most common benign tumor of infancy. The aim of this study is
      to evaluate the biological effects of sodium morrhuate (SM) and its liposomal
      formulation on infantile hemangioma endothelial cells (IHECs). Morphological
      analysis revealed that exposure to liposomal sodium morrhuate (LSM)
      preferentially caused apoptotic death in IHECs, manifested as shrunken
      configuration and formation of apoptotic bodies. In contrast, necrotic death was
      prominent in IHECs treated with an equal concentration of SM. By means of
      proteomic analysis and confirmation experiments, we revealed that the apoptosis
      inducing effects of LSM were associated with an upregulation of a set of genes
      involved in mitochondrial death pathway, including apoptosis-inducing factor,
      cytochrome c1, caspase-8, and lamin B1. In conclusion, our data highlight the
      proapoptotic activity of LSM in IHECs through the mitochondrial apoptotic pathway
      and may provide a promising avenue to treat hemangiomas of infancy.

PMID- 22987599
TI  - Molecular catch and release: controlled delivery using optical trapping with
      light-responsive liposomes.
AB  - Gold-coated liposomes are maneuvered using an optical trap to achieve precise
      delivery of encapsulated molecular cargo. Movement and payload release from these
      plasmon resonant nanocapsules are independently controlled using a pulsed
      trapping beam. This technology enables in vitro delivery of a payload to a
      selected cell and may be applied to the interrogation of individual cells within
      their biological microenvironment.

PMID- 22987600
TI  - Risk for ingestion of toxic substances in children with Prader-Willi syndrome.
AB  - Individuals with Prader-Willi syndrome (PWS) have several common findings that
      may predispose to ingestion of potentially dangerous items. This study examined
      whether individuals with PWS have an increased prevalence of toxic ingestions. A
      survey regarding history of ingestions in PWS individuals and sibling controls
      was designed, piloted, and distributed on-line. The subjects were individuals
      with PWS (N = 129). The subjects' non-PWS siblings served as controls (N = 134).
      Participants who completed the anonymous online survey were either the parents or
      the primary caretaker of individuals with PWS. Responses were submitted by 141
      participants, providing information about 130 PWS subjects (M/F: 66:64) and 134
      sibling controls. Subjects and controls ranged in age from 2 to 18 years at the
      time of the survey. Eleven participants did not answer the questions regarding
      ingestions. History of toxic ingestion was more prevalent in PWS subjects (20%
      vs. 2% of controls). Several features of PWS, including history of searching for
      food and eating unusual objects, along with decreased cognitive ability, appeared
      to associate with increased prevalence of toxic ingestion in PWS individuals. PWS
      children appear to have an ~12-fold increased risk of ingesting toxins compared
      to the general population. Geneticists should include this information in
      counseling and in recommendations to primary care providers. Also, poison control
      centers need to be aware of this association and of the physiological and
      behavioral aspects of PWS that may complicate the diagnosis and management of a
      toxic ingestion.

PMID- 22987601
TI  - The HPV test has similar sensitivity but more overdiagnosis than the Pap test--a
      randomised health services study on cervical cancer screening in Finland.
AB  - We compared test sensitivity (in terms of prevented cancers) and overdiagnosis
      (in terms of non-progressive pre-invasive lesions) between the human
      papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in
      routine screening for cervical cancer. The design was a randomised (1:1) health
      services study in Finland with intake between 2003 and 2007. We estimated
      sensitivity by the incidence method within one screening round. Overdiagnosis was
      based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at
      screen and during the following interval. Out of 203,788 randomised women 132,298
      attended (65% in both study arms) and 600,753 person-years accumulated among
      attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers
      and 288 CIN3 lesions were diagnosed at screen or during the following interval.
      The interval cancer incidence was 2.5/10(5)  person-years (sensitivity 0.87) and
      1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of
      CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV
      testing was similar to that of Pap testing but caused more overdiagnosis.
      Therefore, implementation of HPV testing needs to be reconsidered especially in
      countries with well organised programmes.

PMID- 22987603
TI  - Method development and validation for the quantification of dasatinib, erlotinib,
      gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human
      plasma by liquid chromatography coupled with tandem mass spectrometry.
AB  - To support pharmacokinetic-guided dosing in individual patients, a fast and
      accurate method for simultaneous determination of anticancer tyrosine kinase
      inhibitors (TKIs) dasatinib, erlotinib, gefitinib, imatinib, lapatinib,
      nilotinib, sorafenib and sunitinib in human plasma was developed using high
      performance liquid chromatography and detection with tandem mass spectrometry
      (HPLC-MS/MS). Stable isotopically labeled compounds of the eight different TKIs
      were used as internal standards. Plasma proteins were precipitated and an aliquot
      of supernatant was directly injected onto a reversed phase chromatography system
      consisting of a Gemini C18 column (50 * 2.0 mm i.d., 5.0 um particle size) and
      then compounds were eluted with a gradient. The outlet of the column was
      connected to a triple quadrupole mass spectrometer with electrospray interface.
      Ions were detected in the positive multiple reaction monitoring mode. This method
      was validated over a linear range from 20.0 to 10,000 ng/mL for erlotinib,
      gefitinib, imatinib, lapatinib, nilotinib and sorafenib, and from 5.00 to 2500
      ng/mL for dasatinib and sunitinib. Results from the validation study demonstrated
      good intra- and inter-assay accuracy (<13.1%) and precision (10.0%) for all
      analytes. This method was successfully applied for routine therapeutic drug
      monitoring purposes in patients treated with the investigated TKIs.

PMID- 22987602
TI  - Annual and seasonal evaluation of reproductive status in hornyhead turbot at
      municipal wastewater outfalls in the Southern California Bight.
AB  - Treated wastewater effluent containing endocrine-disrupting chemicals is
      discharged into the coastal waters of the Southern California Bight (SCB) daily.
      The present study investigated changes in indicators of reproductive health and
      environmental estrogen exposure in hornyhead turbot (Pleuronichthys verticalis)
      near wastewater outfalls. Fish were collected from discharge areas, farfield
      stations, and a reference location in the SCB to examine spatial and temporal
      patterns. Fish from the Orange County outfall farfield site were younger and less
      sexually mature than fish from other sites. The sex ratio was skewed in some fish
      from outfall sites as well as from the Dana Point reference site. However, no
      consistent pattern in sex ratio was present over time. Low-level induction of
      vitellogenin was frequently observed in male fish from all sites, suggesting
      widespread exposure to estrogenic compounds, but did not appear to impact
      reproductive function as there was no incidence of gonad abnormalities (ova
      testis). Analysis of historical hornyhead turbot trawl data indicated that
      populations are either increasing or stable in the SCB; thus, environmental
      estrogen exposure was not adversely impacting fish abundance. Additional research
      is needed to determine the cause of the estrogenic response in hornyhead turbot
      and whether the source of the estrogenic compounds is a consequence of historical
      contamination or of ongoing sources or representative of baseline characteristic
      of this species.

PMID- 22987604
TI  - Reversible cyclopropane ring-cleavage reactions within etheno-bridged
      [4.3.1]propelladiene frameworks leading to aza- and oxa
      [5.6.5.6]fenestratetraenes.
AB  - Opening and closing a chemical window: oxidation of the etheno-bridged
      [4.3.1]propelladienol 1 with pyridinium chlorochromate (PCC) affords
      oxa[5.6.5.6]fenestratetraene 2. The reduction of 2 with diisobutylaluminum
      hydride (DIBAl-H) leads to the regeneration of its precursor (1). These
      transformations most likely involve a [3,5]-sigmatropic rearrangement process.

PMID- 22987605
TI  - Polymer grafting to single-walled carbon nanotubes: effect of chain length on
      solubility, graft density and mechanical properties of macroscopic structures.
AB  - Single-walled carbon nanotubes are grafted with polystyrene chains employing a
      graft-to protocol. Thermogravimetric analysis allows calculation of the grafted
      chain density and average interchain separation on the nanotube surface as a
      function of molecular weight. The separation scales with molecular weight as a
      power law with an exponent of ca. 0.588, showing the grafted chains to be in a
      swollen random walk conformation. This implies that chain packing is controlled
      by coil size in solution. In addition, the dispersed concentration of
      functionalized nanotubes scales with the size of the steric potential barrier
      that prevents aggregation of polymer functionalized nanotubes. It is also shown
      that the molecular weight of the grafted chains significantly affects the
      mechanical properties of nanotube films.

PMID- 22987606
TI  - Combining individual patient data and aggregate data in mixed treatment
      comparison meta-analysis: Individual patient data may be beneficial if only for a
      subset of trials.
AB  - BACKGROUND: Individual patient data (IPD) meta-analysis is the gold standard.
      Aggregate data (AD) and IPD can be combined using conventional pairwise meta
      analysis when IPD cannot be obtained for all relevant studies. We extend the
      methodology to combine IPD and AD in a mixed treatment comparison (MTC) meta
      analysis. METHODS: The proposed random-effects MTC models combine IPD and AD for
      a dichotomous outcome. We study the benefits of acquiring IPD for a subset of
      trials when assessing the underlying consistency assumption by including
      treatment-by-covariate interactions in the model. We describe three different
      model specifications that make increasingly stronger assumptions regarding the
      interactions. We illustrate the methodology through application to real data sets
      to compare drugs for treating malaria by using the outcome unadjusted treatment
      success at day 28. We compare results from AD alone, IPD alone and all data.
      RESULTS: When IPD contributed (i.e. either using IPD alone or combining IPD and
      AD), the chains converged, and we identified statistically significant regression
      coefficients for the interactions. Using IPD alone, we were able to compare only
      three of the six treatments of interest. When models were fitted to AD, the
      treatment effects and regression coefficients for the interactions were far more
      imprecise, and the chains did not converge. CONCLUSIONS: The models combining IPD
      and AD encapsulated all available evidence. When exploring interactions, it can
      be beneficial to obtain IPD for a subset of trials and to combine IPD with
      additional AD.

PMID- 22987607
TI  - Sleep-disordered breathing in Beckwith-Wiedemann syndrome: three patients.
AB  - Beckwith-Wiedemann syndrome is associated with craniofacial abnormalities that
      may predispose patients to sleep-related breathing disorders. There is limited
      literature on the polysomnography findings for children with this syndrome. Three
      patients with Beckwith-Wiedemann syndrome underwent polysomnography in our sleep
      lab and were found to have a variety of sleep-disordered breathing that ranged
      from obstructive apnea to isolated REM sleep-related hypoxemia-hypoventilation
      without obstructive apnea. Suspicion for sleep-disordered breathing should be
      high in children with Beckwith-Wiedemann syndrome.

PMID- 22987608
TI  - Carbon isotope ratio analysis of endogenous glucocorticoid urinary metabolites
      after cortisone acetate and adrenosterone administration for doping control.
AB  - Glucocorticoids are listed on the World Anti-Doping Agency (WADA) Prohibited List
      of substances. The detection of the administration of hydrocortisone and
      cortisone is complicated by the fact that the human body also produces these
      steroids naturally. Gas chromatography-combustion-isotope ratio mass spectrometry
      can be utilized to determine the use of endogenous glucocorticoids by measuring
      the carbon isotope ratio (CIR) of their resulting metabolites in human urine
      samples. A comprehensive sample preparation protocol for the analysis of
      endogenous glucocorticoid urinary metabolites was developed and validated,
      incorporating the use of high performance liquid chromatography (HPLC) for
      purification and chemical oxidation for derivatisation. Target compounds were
      tetrahydrocortisol and tetrahydrocortisone, and 11beta-hydroxyetiocholanolone, 11
      oxoetiocholanolone and 11beta-hydroxyandrosterone, while pregnanediol functioned
      as the endogenous reference compound. Urine samples from a population of 50
      volunteers were analyzed to determine CIR reference limits. Excretion studies of
      the endogenous glucocorticoid preparation cortisone acetate (25 mg oral) and the
      dietary supplement adrenosterone (75 mg oral) were conducted with six male
      individuals. Variable changes in steroid metabolite isotopic composition were
      found across subjects after administration. The study also revealed that CIR
      analysis of the major glucocorticoid metabolites tetrahydrocortisol and
      tetrahydrocortisone is necessary to unambiguously distinguish administration of
      cortisone and adrenosterone, the former officially restricted to out-of
      competition use by athletes, the latter not being restricted at the current time.
      Moreover, this study reaffirms that CIR methods for the doping control of
      endogenous steroids should not rely upon a single ERC, as the administration of
      an appropriate precursor to that ERC could cause complications during analysis.

PMID- 22987609
TI  - Accuracy of percutaneous core needle biopsy in diagnosing papillary breast
      lesions and potential impact of sonographic features on their management.
AB  - OBJECTIVE: To assess retrospectively the accuracy of core needle biopsy in
      diagnosing papillary breast lesions and evaluate the prediction of malignant
      papillary lesions based on sonographic features. METHODS: Review of 130 papillary
      lesions diagnosed on core needle biopsy (2002-2008) in 110 patients. The biopsy
      results were compared with final surgical pathology or evolution on imaging
      follow-up. Lesion size, patient age, type of biopsy needle and guidance, and
      length of imaging follow-up were documented. Sonographic features were
      retrospectively reviewed according to the BI-RADS lexicon. Morphology, not part
      of BI-RADS, was assessed as intraductal, intracystic, or solid. RESULTS: Of the
      130 papillary lesions, 6 were sampled with an 11-G vacuum-assisted needle under
      stereotactic guidance and the remaining 124 were sampled under US guidance with a
      14-G (n = 115), 18-G (n = 8), or 10-G (n = 1) needle. Initial core needle biopsy
      diagnosis was benign (n = 103), showed atypia (n = 20), or malignancy (n = 7).
      Thirty-seven (36%) benign lesions were surgically excised and 66 (64%) were
      followed up. On final outcome, 10 benign lesions were upgraded to malignancy
      (9.7%) and 3 to atypia (3.6%). There was no significant difference in the benign,
      malignant, and upgraded groups with respect to size, age, or BI-RADS sonographic
      characteristics. None of the oval-shaped lesions nor the intraductal ones were
      upgraded. CONCLUSIONS: Although some sonographic features could favor a benign
      diagnosis, when a core biopsy yields the diagnosis of a papillary lesion,
      surgical excision is recommended to definitely exclude malignancy.

PMID- 22987610
TI  - Vertically aligned Ta3N5 nanorod arrays for solar-driven photoelectrochemical
      water splitting.
AB  - A vertically aligned Ta(3)N(5) nanorod photoelectrode is fabricated by through
      mask anodization and nitridation for water splitting. The Ta(3)N(5) nanorods,
      working as photoanodes of a photoelectrochemical cell, yield a high photocurrent
      density of 3.8 mA cm(-2) at 1.23 V versus a reversible hydrogen electrode under
      AM 1.5G simulated sunlight and an incident photon-to-current conversion
      efficiency of 41.3% at 440 nm, one of the highest activities reported for
      photoanodes so far.

PMID- 22987611
TI  - Integrated coastal effects study: synthesis of findings.
AB  - Municipal wastewater discharges constitute a major source of contaminants of
      emerging concern (CECs) to coastal waters, yet uncertainty exists regarding their
      linkage to adverse biological effects such as endocrine disruption. Limited
      information is available concerning the types and fate of CECs discharged to the
      Southern California Bight (SCB) from municipal wastewater and their potential for
      ecological impacts. The present study investigated the impacts of CECs from ocean
      wastewater discharges on SCB fish. Concentrations of CECs were measured in
      effluents from four major municipal wastewater dischargers. Seawater, sediment,
      and hornyhead turbot (Pleuronichthys verticalis) from the discharge sites and a
      reference area were collected and analyzed for chemical and biological
      indicators. Low concentrations of pharmaceuticals, personal care products, and
      industrial and commercial compounds were measured in effluent. Some CECs were
      also detected in sediment, seawater, and fish livers near the outfalls,
      confirming exposure to CECs. Fish plasma hormone analyses suggested the presence
      of physiological effects, including a reduced stress response, altered estrogen
      synthesis or estrogenic exposure, and reduced thyroxine. Most fish responses were
      found at all sites and could not be directly associated with effluent discharges.
      However, concentrations of thyroxine were lower at all discharge sites relative
      to the reference, and estradiol concentrations were lower at three of the four
      outfall sites. The physiological responses found were not associated with adverse
      impacts on fish reproduction or populations. Interpretation of molecular and
      physiological measurements in field organisms such as those used in the present
      study is challenging because of a lack of information on baseline conditions and
      uncertain linkages to apical endpoints such as survival and reproduction.

PMID- 22987612
TI  - Responsiveness of hepatic and cerebral cytochrome P450 in rat offspring
      prenatally and lactationally exposed to a reconstituted PCB mixture.
AB  - Perinatal polychlorinated biphenyl (PCB) exposures still remain a serious health
      concern because offspring receive PCB burden from mother during vulnerable
      processes of development. Since cytochrome P450 (CYP) represents a toxicological
      endpoint, in the present study, representing an extended investigation of a
      previous multitasked one, we explored the long-term responsiveness of CYP1A and
      CYP2B isoforms by Western blot analysis in liver and whole brain of lactating
      (PN12), weaning (PN21), and adult offspring (PN60) rats prenatally and
      lactationally exposed to a reconstituted PCB mixture (RM) of noncoplanar PCB138,
      153, 180, and coplanar PCB126 congeners. We chose highly chlorinated PCBs instead
      of lower chlorinated one, because their recalcitrance to biotransformation makes
      easy their accumulation/persistence in tissues and breast milk. Dioxin-like
      congener PCB126 binding aryl hydrocarbon receptor (AHR) is responsible of many
      toxic effects. Pregnant Sprague-Dawley dams with high affinity AHR received
      subcutaneous injection of RM (10 mg/kg body weight) daily during gestation (days
      15-19) and twice a week during breast-feeding. The results evidenced a transfer
      of PCBs to neonates through milk and a significant responsiveness of hepatic CYP
      in both mothers and offspring. In liver of exposed progeny, CYP isoforms
      exhibited a significant increment at PN12 (70% over control) and at PN21 (270%
      over control). Contrary to dams, in adult PCB offspring CYP levels showed a
      decline up to values similar to those of control. This transient developmental
      responsiveness of CYP isoforms in offspring liver reflects roughly the time
      course of hepatic PCB levels previously reported. Even if congeners were detected
      in brain, we failed in evidencing a responsiveness of CYP isoforms probably
      because of region-specific CYP expression in this organ. In conclusion, induction
      of offspring hepatic CYP is index of liver PCB burden, and despite the
      insensitivity of whole brain CYP we cannot exclude brain vulnerability toward
      PCB. (c) 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 856-866, 2014. 

PMID- 22987613
TI  - Three unrelated patients with congenital anterior pituitary aplasia and a
      characteristic physical and neuropsychological phenotype: a new syndrome?
AB  - Anterior pituitary aplasia (APA) is a very rare cause of congenital-onset
      multiple pituitary hormone deficiency (CO-MPHD). We report on molecular analysis
      and clinical follow-up of three previously reported cases of APA [Scommegna et
      al., 2004], who share a characteristic physical and neuropsychological profile.
      Mutation analysis of genes encoding transcription factors involved in pituitary
      development (PROP1, POUF1, HESX1, LHX3, and LHX4) did not demonstrate a any
      mutation. In order to identify the genetic cause underlying the phenotypes we
      performed an array-based comparative genomic hybridization (array-CGH), which
      showed a cryptic interstitial deletion of 9p (200 kb), including the TEK and
      MOBKL2B, in one patient. Although an apparently identical deletion was carried by
      the clinically normal father, we assumed that the patient's phenotype might be
      due to a recessive mutation in the other allele. However, sequence analysis of
      exons and splice junctions of these genes did not detect pathogenic or
      predisposing variants in the three patients. We suggest that the constellation of
      clinical signs in these patients constitutes a previously undescribed syndrome,
      whose genetic cause has yet to be identified.

PMID- 22987614
TI  - An efficient method for purification of nonspecific lipid transfer protein-1 from
      rice seeds using kiwifruit actinidin proteolysis and ion exchange chromatography.
AB  - Plant nonspecific lipid transfer proteins are small basic proteins that transport
      phospholipids between membranes and are subdivided into two subfamilies, nsLTP(1)
      (9 kDa) and nsLTP(2) (7 kDa). LTPs have potential application in the defense
      reactions against pathogens and the drug delivery systems. Many efforts have been
      made for purification of different nsLTPs from various plants; however, most of
      them used successive purification procedures. We have developed a relatively
      simple and efficient method for the purification of rice nsLTP(1), based on the
      proteolytic activity of kiwifruit actinidin on the rice seed extract and one-step
      chromatographic procedure on a CM-Sepharose column. The purity of protein was
      determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The
      isolated LTP(1) migrated as a homogenous polypeptide with molecular mass of 9 kDa
      that confirms the efficiency of actinidin on the digestion of major
      contaminations present in the rice seed extract without any harmful effect on the
      LTP(1). The advantages of using proteolytic activity of actinidin in purifying
      rice LTP(1) includes the reduced separation time allowing the purification of
      LTP(1) in one-step chromatographic procedure, low costing, high efficiency, and
      the relative simplicity of the method.

PMID- 22987616
TI  - Enantioselective construction of pyrroloindolines catalyzed by chiral phosphoric
      acids: total synthesis of (-)-debromoflustramine B.

PMID- 22987615
TI  - Deletion of the RNA-editing enzyme ADAR1 causes regression of established chronic
      myelogenous leukemia in mice.
AB  - Patients with chronic myelogenous leukemia (CML) respond well to tyrosine kinase
      inhibitors (TKIs) of the Bcr-Abl oncoprotein. However, intolerance and resistance
      to these agents remains a challenge, and TKIs are unable to eradicate rare
      leukemia-initiating cells. Leukemia treatment would benefit from a better
      understanding of molecular signals that are necessary for the survival of
      leukemia-initiating cells but dispensable for normal hematopoietic stem cells.
      Leukemia-initiating cells in CML can arise from myeloid progenitor cells, a
      population that we have reported in normal hematopoiesis to depend on the RNA
      editing enzyme adenosine deaminase acting on RNA-1 (ADAR1). We now report that
      Bcr-Abl transformed leukemic cells were ADAR1-dependent in a conditional ADAR1
      knockout mouse model. ADAR1 deletion reversed leukocytosis and splenomegaly, and
      preferentially depleted primitive Lin-Sca+Kit+ (LSK) leukemic cells but not LSK
      cells lacking the leukemic oncoprotein. ADAR1 deletion ultimately normalized the
      peripheral white blood count, eliminating leukemic cells as assessed by PCR.
      These results uncover a novel requirement for ADAR1 in myeloid leukemic cells and
      indicate that ADAR1 may comprise a new molecular target for CML-directed
      therapeutics.

PMID- 22987617
TI  - Identification of upregulated genes in oral squamous cell carcinomas.
AB  - BACKGROUND: Oral cancer is the most common subset of head and neck squamous cell
      carcinomas (HNSCC). These tumors often have an aggressive clinical outcome
      hallmarked by a propensity for local invasion and regional nodal metastasis.
      Upregulated genes could be useful as markers for diagnosis, prognosis, and as new
      drug targets for these tumors. METHODS: To identify upregulated genes in oral
      squamous cell carcinomas (OSSCs), we examined the ORESTES public database and
      used a quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
      approach to determine the expression level of selected genes in tumor samples.
      RESULTS AND CONCLUSIONS: The ORESTES data mining analysis indicated 40
      upregulated genes in HNSCC. Nine of these candidate genes were selected for
      further qRT-PCR validation and 3 of them (ALDOA, AHSA1, and POLQ) were frequently
      found upregulated in OSCC samples, which may indicate an association of these
      genes with the carcinogenesis process in this tumor site and they can constitute
      potential new targets for therapy.

PMID- 22987619
TI  - Submission of scientifically sound and ethical manuscripts to peer-reviewed
      journals - a reviewer's personal perspective on bioanalytical publications.
AB  - In the pharmaceutical industry, bioanalysis is very dynamic and is probably one
      of the few fields of research covering the entire drug discovery, development and
      post-marketing process. Important decisions on drug safety can partially rely on
      bioanalytical data, which therefore can be subject to regulatory scrutiny.
      Bioanalytical scientists have historically contributed significant numbers of
      scientific manuscripts in many peer-reviewed analytical journals. All of these
      journals provide some high-level instructions, but they also leave sufficient
      flexibility for reviewers to perform independent critique and offer
      recommendations for each submitted manuscript. Reviewers play a pivotal role in
      the process of bioanalytical publication to ensure the publication of high
      quality manuscripts in a timely fashion. Their efforts usually lead to improved
      manuscripts. However, it has to be a joint effort among authors, reviewers and
      editors to promote scientifically sound and ethically fair bioanalytical
      publications. Most of the submitted manuscripts were well written with only minor
      or moderate revisions required for further improvement. Nevertheless, there were
      small numbers of submitted manuscripts that did not meet the requirements for
      publications because of scientific or ethical deficiencies, which are discussed
      in this Letter to the Editor.

PMID- 22987618
TI  - Bias correction to secondary trait analysis with case-control design.
AB  - In genetic association studies with densely typed genetic markers, it is often of
      substantial interest to examine not only the primary phenotype but also the
      secondary traits for their association with the genetic markers. For more
      efficient sample ascertainment of the primary phenotype, a case-control design or
      its variants, such as the extreme-value sampling design for a quantitative trait,
      are often adopted. The secondary trait analysis without correcting for the sample
      ascertainment may yield a biased association estimator. We propose a new method
      aiming at correcting the potential bias due to the inadequate adjustment of the
      sample ascertainment. The method yields explicit correction formulas that can be
      used to both screen the genetic markers and rapidly evaluate the sensitivity of
      the results to the assumed baseline case-prevalence rate in the population.
      Simulation studies demonstrate good performance of the proposed approach in
      comparison with the more computationally intensive approaches, such as the
      compensator approaches and the maximum prospective likelihood approach. We
      illustrate the application of the approach by analysis of the genetic association
      of prostate specific antigen in a case-control study of prostate cancer in the
      African American population.

PMID- 22987620
TI  - Haploinsufficiency of STK11 and neighboring genes cause a contiguous gene
      syndrome including Peutz-Jeghers phenotype.
AB  - We report on clinical and molecular findings of a 15-year-old female referred to
      our genetics clinic for a diagnostic evaluation due to mild developmental delay,
      submucosal cleft palate, and seizure disorder. Chromosomal microarray technology
      revealed a cancer predisposition due to a terminal deletion on chromosome 19p
      that includes the tumor suppressor gene STK11. In addition to abnormal lip
      pigmentation on exam, further diagnostic workup with upper and lower
      gastrointestinal screening confirmed polyps consistent with Peutz-Jeghers
      syndrome. The purpose of this study is to present a full clinical description of
      a patient with a rare 19p13.3 chromosomal deletion and review the current
      literature of this newly emerging contiguous gene deletion syndrome. It also
      supports the screening for complications of Peutz-Jeghers syndrome in all
      patients with this deletion.

PMID- 22987621
TI  - Application of electrospray ionization product ion spectra for identification
      with atmospheric pressure matrix-assisted laser desorption/ionization mass
      spectrometry - a case study with seized drugs.
AB  - Product ion spectra obtained with liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC-ESI/MS/MS) were applied to the identification of
      seized drug samples from atmospheric pressure matrix-assisted laser
      desorption/ionization product ion spectra (AP-MALDI-MS/MS spectra). Data
      acquisition was performed in the information-dependent acquisition (IDA) mode,
      and the substance identification was based on a spectral library previously
      created with LC-ESI/MS/MS using protonated molecules as precursor ions. A total
      of 39 seized drug samples were analyzed with both AP-MALDI and LC-ESI techniques
      using the same triple-quadrupole instrument (AB Sciex 4000QTRAP). The study shows
      that ESI-MS/MS spectra can be directly utilized in AP-MALDI-MS/MS measurements as
      the average fit and purity score percentages with AP-MALDI were 90% and 85%,
      respectively, being similar to or even better than those obtained with the
      reference LC/ESI-MS/MS method. This fact enables the possibility to use large ESI
      spectral libraries, not only to ESI analyses but also to analyses with other
      ionization techniques which produce protonated molecules as the base peak. The
      data obtained shows that spectral library search works also for analytical
      techniques which produce multi-component mass spectra, such as AP-MALDI, unless
      isobaric compounds are encountered. The spectral library search was successfully
      applied to rapid identification of confiscated drugs by AP-MALDI-IDA-MS/MS.

PMID- 22987622
TI  - Bistable large-strain actuation of interpenetrating polymer networks.
AB  - The bistable electroactive polymer is a new smart material capable of large
      strain, rigid-to-rigid actuation. At the rubbery state of the polymer heated to
      above its glass transition, stable electrically-induced actuation is obtained at
      strains as large as 150%. Electromechanical instability can be effectively
      overcome by the formation of interpenetrating polymer networks. An application as
      a refreshable braille display is demonstrated.

PMID- 22987623
TI  - Prognostic value of acute fluid collections diagnosed by ultrasound in the early
      assessment of severity of acute pancreatitis.
AB  - PURPOSE: To evaluate the prognostic value of acute fluid collections (AFC)
      diagnosed by conventional transabdominal ultrasound in the early assessment of
      severity acute pancreatitis (AP). METHODS: We studied 128 consecutive patients
      with AP between March 2006 and March 2011. The predictor was the number of AFC.
      Outcome measure was the occurrence of complications. Abdominal sonogram, contrast
      enhanced CT, and pancreatitis-specific clinical and laboratory findings were
      performed. RESULTS: AFC were associated with complications (p < 0.0001),
      Balthazar grade (p = 0.004), Ranson score (p < 0.0001), and the majority of
      clinical, radiologic, and biochemical parameters for predicting complications of
      AP (p < 0.05). Univariate logistic regression also revealed significant
      association between the number of AFC and the occurrence of complications (OR
      4.4; 95% CI 2.5-7.6). After the adjustment for covariates, AFC remained
      prognostic for complications and a cutoff point of >1 AFC was prognostic of their
      occurrence with 88% sensitivity and 82% specificity. CONCLUSIONS: AFC are related
      to the clinical course of AP and can predict its severity

PMID- 22987624
TI  - Evaluation of reproductive endocrine status in hornyhead turbot sampled from
      Southern California's urbanized coastal environments.
AB  - As part of a regionwide collaboration to determine the occurrence of contaminants
      and biological effects in coastal ecosystems offshore of urban southern
      California, the present study characterized the reproductive endocrinology of an
      indigenous flatfish, the hornyhead turbot (Pleuronichthys verticalis), and
      compared groups sampled from different study sites representing varying degrees
      of pollution to screen for potential endocrine disruptive effects. Turbot were
      sampled from locations near the coastal discharge sites of four large municipal
      wastewater treatment plants (WWTPs) located between Los Angeles and San Diego,
      California, USA, and were compared with fish sampled from three far-field
      reference locations in the region. Despite environmental presence of both legacy
      contaminants and contaminants of emerging concern and evidence for fish exposure
      to several classes of contaminants, both males and females generally exhibited
      coordinated seasonal reproductive cycles at all study sites. Patterns observed
      included peaks in sex steroids (17beta-estradiol, testosterone, 11
      ketotestosterone) in the spring and low levels in the fall, changes corresponding
      to similarly timed gonadal changes and plasma vitellogenin concentrations in
      females. Comparisons between fish captured at the different study sites
      demonstrated some regional differences in plasma levels of estrogens and
      androgens, indicative of location-associated effects on the endocrine system. The
      observed differences, however, could not be linked to the ocean discharge
      locations of four of the largest WWTPs in the world.

PMID- 22987625
TI  - Unstable transmission of a familial complex chromosome rearrangement.
AB  - Complex chromosome rearrangements (CCRs) are rare genomic structural aberrations
      involving three or more breakpoints on two or more chromosomes. About one-third
      of all CCRs are familial. Transmittance of such a CCR results either in genomic
      imbalance due to abnormal segregation at meiosis I or is stably passed on to the
      next generation. Here we present a phenotypically normal mother with a CCR
      involving chromosomes 1, 3, and 5 that gave birth to a phenotypically abnormal
      son. The boy presented with hypotonia, mild facial dysmorphisms, and severe
      intellectual disability. Conventional karyotyping revealed the same apparently
      balanced CCR as in the mother. However, by use of array-comparative genome
      hybridization (array-CGH) and fluorescence in situ hybridization (FISH) we
      discovered that one of the derivative chromosomes in the patient contained a de
      novo rearrangement. It appears that during transmission of the CCR, an additional
      de novo deletion and duplication had arisen in one of the derivative chromosomes.
      We speculate that this was the result of the inverted duplication with a distal
      deletion mechanism. We also demonstrate the importance of high-resolution
      breakpoint analysis in CCRs and stress that genetic counseling of a familial CCR
      is not straightforward. To our knowledge, this would be the first description of
      this mechanism operating on a structurally abnormal chromosome.

PMID- 22987626
TI  - Comparative evaluation in vitro of the herbicide flurochloridone by cytokinesis
      block micronucleus cytome and comet assays.
AB  - The in-vitro effects of flurochloridone and its formulations Twin Pack Gold(r)
      (25% a.i.) and Rainbow(r) (25% a.i.) were evaluated in Chinese Hamster Ovary K1
      (CHO-K1) cells. The cytokinesis-block micronucleus cytome (CBMN-cyt) and single
      cell gel electrophoresis (SCGE) assays were used. The activities were tested
      within the range of final concentrations of 0.25-15 MUg flurochloridone/mL. The
      results demonstrated that both the flurochloridone and Rainbow(r) were not able
      to induce micronuclei (MN). On the other hand, Twin Pack Gold(r) only increased
      the frequency of MN at 5 MUg/mL. Furthermore, 10 and 15 MUg/mL of both
      formulations resulted in a cellular cytotoxicity demonstrated by alterations in
      the nuclear division index and cellular death. SCGE assay appeared to be a more
      sensitive bioassay for detecting primary DNA strand breaks at lower
      concentrations of flurochloridone than MN did. A marked increase in the genetic
      damage index was observed when 5 and 15 MUg/mL of both flurochloridone and
      Rainbow(r) but only when 15 MUg/mL of Twin Pack Gold(r) were used. This is the
      first report demonstrating that flurochloridone and its two commercial
      formulations are able to induce single-strand DNA breaks in vitro on mammalian
      cells.

PMID- 22987627
TI  - Early gonadogenesis in mammals: significance of long and narrow gonadal
      structure.
AB  - In mammalian embryogenesis, the gonadal primordium arises from the thickening of
      the coelomic epithelium, which results in a pair of extremely long and narrow
      gonadal structures along the anteroposterior axis. These gonadal structures are
      conserved in various mammalian species, suggesting a great advantage in properly
      receiving migrating primordial germ cells (PGCs) that are widely scattered
      throughout the hindgut tube. Soon after the PGCs settle, the bipotential gonads
      undergo sex determination into testes or ovaries by the sex-determining gene,
      Sry, which is expressed in supporting cell precursors in a center-to-pole manner.
      Such a long, narrow gonadal structure bestows a considerable time lag on Sry
      expression between the center and pole regions, but testiculogenesis with cord
      formation and Leydig cell differentiation occurs synchronously throughout the
      whole organ. This synchronous testiculogenesis could be explained by a positive
      feedback mechanism between SOX9 (another SRY-related transcription factor) and
      FGF9 downstream of Sry. FGF signals are likely secreted from the center region,
      rapidly diffuse into the poles, and then induce the establishment of SOX9
      expression in Sertoli cells in the pole domains. This work focuses on recent
      knowledge of the molecular and cellular events of PGC migration, gonadogenesis,
      and testiculogenesis, and their biological significance in mammalian
      embryogenesis.

PMID- 22987628
TI  - EPCAM-A novel molecular target for the treatment of pediatric and adult germ cell
      tumors.
AB  - Germ cell tumors (GCTs) are thought to develop from totipotent primordial germ
      cells. Although the epithelial cell adhesion molecule (EPCAM) is expressed on
      embryonic stem cells as well as different tumor cells, it has not yet been
      extensively studied in GCTs. We analyzed EPCAM expression by quantitative RT-PCR
      in 48 fresh-frozen GCT specimens of different histology (10 mature teratoma, MT;
      6 immature teratoma, IT; 7 dysgerminoma; 6 mixed malignant GCTs; 19 yolk sac
      tumor, YST) and in the GCT cell lines NCCIT, TE76.T, JAR and 2102Ep, and
      correlated its expression with AFP and hCG protein levels, histologic
      differentiation, and clinical follow-up data. EPCAM protein was visualized by
      immunohistochemistry of selected corresponding paraffin embedded tumor tissues.
      EPCAM was expressed in malignant but not in benign GCTs irrespective of age, sex,
      site and clinical stage of tumor (P = 0.001). In primary teratomas, EPCAM
      expression increased with their grade of immaturity (mean 2(-DeltaCt) values: MT
      0.23, IT 1.61, P = 0.007) and significantly correlated with serum AFP (P = 0.03)
      and hCG (P = 0.03) levels in malignant GCTs. Particularly high EPCAM levels were
      found in nonseminomatous GCTs such as YSTs (8.49) and choriocarcinoma (13.54).
      Immunohistochemical analysis verified gene expression data showing a distinct
      EPCAM staining in YST. Similarly in vitro, highest EPCAM expression was measured
      in GCT cell lines comprising yolk sac (2102Ep: 5.59) or choriocarcinoma (JAR:
      10.65) components. This first comprehensive analysis of EPCAM in GCTs revealed
      high EPCAM expression in YSTs and choriocarcinomas. Thus, these nonseminomatous
      GCTs may be interesting targets for EPCAM immunotherapy, which has to be
      evaluated in further studies.

PMID- 22987629
TI  - Gold vinylidene complexes: intermolecular C(sp3)-H insertions and
      cyclopropanations pathways.
AB  - Highly reactive gold vinylidene species are used for intermolecular C(sp(3))-H
      insertions into unactivated alkanes (see scheme). In addition, they can be
      regarded as synthons for alkylidene carbenes. Initiated by cyclopropanation of
      the vinylidene species/alkylidene carbenoide, cyclobutene derivatives are formed
      in a diastereoselective fashion by a ring-enlargement cascade in only one step.

PMID- 22987630
TI  - Are we ready for targeted early breast cancer detection strategies in women with
      NF1 aged 30-49 years?

PMID- 22987631
TI  - Assessing overall evidence from noninferiority trials with shared historical
      data.
AB  - For regulatory approval of a new drug, the United States Code of Federal
      Regulations (CFR) requires 'substantial evidence' from 'adequate and well
      controlled investigations'. This requirement is interpreted in the Food and Drug
      Administration guidance as the need of 'at least two adequate and well-controlled
      studies, each convincing on its own to establish effectiveness'. The guidance
      also emphasizes the need of 'independent substantiation of experimental results
      from multiple studies'. However, several authors have noted the loss of
      independence between two noninferiority trials that use the same set of
      historical data to make inferences, raising questions about whether the CFR
      requirement is met in noninferiority trials through current practice. In this
      article, we first propose a statistical interpretation of the CFR requirement in
      terms of trial-level and overall type I error rates, which captures the essence
      of the requirement and can be operationalized for noninferiority trials. We next
      examine four typical regulatory settings in which the proposed requirement may or
      may not be fulfilled by existing methods of analysis (fixed margin and
      synthesis). In situations where the criteria are not met, we then propose
      adjustments to the existing methods. As illustrated with several examples, our
      results and findings can be helpful in designing and analyzing noninferiority
      trials in a way that is both compliant with the regulatory interpretation of the
      CFR requirement and reasonably powerful.

PMID- 22987632
TI  - GPSM2 mutations in Chudley-McCullough syndrome.

PMID- 22987633
TI  - The p53 family grows old.
AB  - p73 and p63 are evolving members of the p53 tumor suppressor family. TAp73 is a
      p73 isoform with a potent transcriptional activation domain, and loss of TAp73
      predisposes mice to tumor development. In this issue of Genes & Development,
      Rufini and colleagues (pp. 2009-2014) discuss how TAp73-null mice display an
      aging phenotype that is due to mitochondrial dysfunction. Specifically, decreased
      levels of cytochrome C oxidase subunit 4 isoform 1 (Cox4i1) impair cytochrome C
      oxidase (COX) function, the multimeric enzyme that executes the last step in
      aerobic respiration. An emerging theme is that defects in metabolism account for
      both cancer and aging.

PMID- 22987634
TI  - Peroxiredoxins, gerontogenes linking aging to genome instability and cancer.
AB  - Age is the highest risk factor known for a large number of maladies, including
      cancers. However, it is unclear how aging mechanistically predisposes the
      organism to such diseases and which gene products are the primary targets of the
      aging process. Recent studies suggest that peroxiredoxins, antioxidant enzymes
      preventing tumor development, are targets of age-related deterioration and that
      bolstering their activity (e.g., by caloric restriction) extends cellular life
      span. This review focuses on how the peroxiredoxin functions (i.e., as
      peroxidases, signal transducers, and molecular chaperones) fit with contemporary
      theories of aging and whether peroxiredoxins could be targeted therapeutically in
      the treatment of age-associated cancers.

PMID- 22987635
TI  - TAp73 depletion accelerates aging through metabolic dysregulation.
AB  - Aging is associated with impaired scavenging of reactive oxygen species (ROS).
      Here, we show that TAp73, a p53 family member, protects against aging by
      regulating mitochondrial activity and preventing ROS accumulation. TAp73-null
      mice show more pronounced aging with increased oxidative damage and senescence.
      TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial
      complex IV activity, with increased ROS production and oxidative stress
      sensitivity. We show that the mitochondrial complex IV subunit cytochrome C
      oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown
      phenocopies the cellular senescence of TAp73-null cells. Results indicate that
      TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating
      aging.

PMID- 22987636
TI  - Dynein mediates the localization and activation of mTOR in normal and human
      cytomegalovirus-infected cells.
AB  - Activation of stress signaling pathways normally leads to inhibition of the
      mammalian target of rapamycin complex 1 (mTORC1); however, human cytomegalovirus
      (HCMV) infection maintains mTORC1 activity in the presence of numerous types of
      stress. We previously demonstrated that HCMV infection maintains mTORC1 activity
      during amino acid deprivation through a Ras-related GTP-binding (Rag) protein
      independent mechanism. This depends on the colocalization of mTOR and its
      activator, Rheb (Ras homology enriched in brain)-GTP, to a perinuclear position
      that corresponds to the viral cytoplasmic assembly compartment (AC). The data
      presented here show that the HCMV-induced, amino acid depletion-resistant
      perinuclear localization and activation of mTORC1 occurs as early as 8 h post
      infection, prior to AC formation. We show that the molecular motor dynein is
      required for perinuclear localization of mTORC1 in both uninfected and HCMV
      infected cells. Association between dynein and mTOR is shown by
      coimmunoprecipitation, and inhibition of dynein function using RNAi or the small
      molecule inhibitor ciliobrevin A inhibits mTORC1 activity in both uninfected and
      HCMV-infected cells. The data suggest that mTORC1 activation requires dynein
      dependent transport to a position in the cell where it can be activated. Thus,
      the HCMV commandeers a cellular dynein-dependent mTORC1 activation mechanism to
      maintain stress-resistant mTORC1 activity during infection and to form the AC.

PMID- 22987637
TI  - Telomere-binding protein Taz1 controls global replication timing through its
      localization near late replication origins in fission yeast.
AB  - In eukaryotes, the replication of chromosome DNA is coordinated by a replication
      timing program that temporally regulates the firing of individual replication
      origins. However, the molecular mechanism underlying the program remains elusive.
      Here, we report that the telomere-binding protein Taz1 plays a crucial role in
      the control of replication timing in fission yeast. A DNA element located
      proximal to a late origin in the chromosome arm represses initiation from the
      origin in early S phase. Systematic deletion and substitution experiments
      demonstrated that two tandem telomeric repeats are essential for this repression.
      The telomeric repeats recruit Taz1, a counterpart of human TRF1 and TRF2, to the
      locus. Genome-wide analysis revealed that Taz1 regulates about half of
      chromosomal late origins, including those in subtelomeres. The Taz1-mediated
      mechanism prevents Dbf4-dependent kinase (DDK)-dependent Sld3 loading onto the
      origins. Our results demonstrate that the replication timing program in fission
      yeast uses the internal telomeric repeats and binding of Taz1.

PMID- 22987638
TI  - Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant
      cells and defines multipotent progenitors in the developing placenta.
AB  - Developmental arrest of Blimp1/Prdm1 mutant embryos at around embryonic day 10.5
      (E10.5) has been attributed to placental disturbances. Here we investigate
      Blimp1/Prdm1 requirements in the trophoblast cell lineage. Loss of function
      disrupts specification of the invasive spiral artery-associated trophoblast giant
      cells (SpA-TGCs) surrounding maternal blood vessels and severely compromises the
      ability of the spongiotrophoblast layer to expand appropriately, secondarily
      causing collapse of the underlying labyrinth layer. Additionally, we identify a
      population of proliferating Blimp1(+) diploid cells present within the
      spongiotrophoblast layer. Lineage tracing experiments exploiting a novel
      Prdm1.Cre-LacZ allele demonstrate that these Blimp1(+) cells give rise to the
      mature SpA-TGCs, canal TGCs, and glycogen trophoblasts. In sum, the
      transcriptional repressor Blimp1/Prdm1 is required for terminal differentiation
      of SpA-TGCs and defines a lineage-restricted progenitor cell population
      contributing to placental growth and morphogenesis.

PMID- 22987639
TI  - Autonomous and nonautonomous roles of Hedgehog signaling in regulating limb
      muscle formation.
AB  - Muscle progenitor cells migrate from the lateral somites into the developing
      vertebrate limb, where they undergo patterning and differentiation in response to
      local signals. Sonic hedgehog (Shh) is a secreted molecule made in the posterior
      limb bud that affects patterning and development of multiple tissues, including
      skeletal muscles. However, the cell-autonomous and non-cell-autonomous functions
      of Shh during limb muscle formation have remained unclear. We found that Shh
      affects the pattern of limb musculature non-cell-autonomously, acting through
      adjacent nonmuscle mesenchyme. However, Shh plays a cell-autonomous role in
      maintaining cell survival in the dermomyotome and initiating early activation of
      the myogenic program in the ventral limb. At later stages, Shh promotes slow
      muscle differentiation cell-autonomously. In addition, Shh signaling is required
      cell-autonomously to regulate directional muscle cell migration in the distal
      limb. We identify neuroepithelial cell transforming gene 1 (Net1) as a downstream
      target and effector of Shh signaling in that context.

PMID- 22987641
TI  - Self-reported family socioeconomic status, the 5-HTTLPR genotype, and delinquent
      behavior in a community-based adolescent population.
AB  - Twin and adoption studies have demonstrated a significant contribution of both
      genetic and environmental factors to antisocial and delinquent behavior.
      Associations have been reported between the serotonin transporter (5-HTT) and
      aggression, and between socioeconomic status (SES), aggression, and serotonergic
      functions of the brain. We aimed to investigate associations between the 5-HTTLPR
      genotype and family SES in relation to delinquent behavior among adolescents. A
      total of 1,467 17- to 18-year-old students in the county of Vastmanland, Sweden,
      anonymously completed a questionnaire and gave a saliva sample. Family SES had a
      U-shaped relation to delinquency, where adolescents with low and high family SES
      were the most delinquent. There were curvilinear interactions between the 5
      HTTLPR genotype and family SES in relation to delinquency. Among individuals
      having high family SES, boys with the LL (homozygous for the long allele) or LS
      (heterozygous) genotypes and girls with the SS (homozygous for the short allele)
      or LS (heterozygous) genotypes showed the highest delinquency scores. Among
      individuals having low family SES, boys with the LL (homozygous for the long
      allele) genotype and girls with the LS (heterozygous) genotype showed the highest
      delinquency scores. The present study suggests evidence for an interaction
      between family SES and the 5-HTTLPR genotype in relation to juvenile delinquency.

PMID- 22987642
TI  - Introduction to this issue: violent and aggressive behaviors in women - part II.

PMID- 22987640
TI  - Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb
      muscle diversity.
AB  - How muscle diversity is generated in the vertebrate body is poorly understood. In
      the limb, dorsal and ventral muscle masses constitute the first myogenic
      diversification, as each gives rise to distinct muscles. Myogenesis initiates
      after muscle precursor cells (MPCs) have migrated from the somites to the limb
      bud and populated the prospective muscle masses. Here, we show that Sonic
      hedgehog (Shh) from the zone of polarizing activity (ZPA) drives myogenesis
      specifically within the ventral muscle mass. Shh directly induces ventral MPCs to
      initiate Myf5 transcription and myogenesis through essential Gli-binding sites
      located in the Myf5 limb enhancer. In the absence of Shh signaling, myogenesis is
      delayed, MPCs fail to migrate distally, and ventral paw muscles fail to form.
      Thus, Shh production in the limb ZPA is essential for the spatiotemporal control
      of myogenesis and coordinates muscle and skeletal development by acting directly
      to regulate the formation of specific ventral muscles.

PMID- 22987643
TI  - Quantitative estimation of gymnemagenin in Gymnema sylvestre extract and its
      marketed formulations using the HPLC-ESI-MS/MS method.
AB  - INTRODUCTION: Gymnema sylvestre, with gymnemic acids as active pharmacological
      constituents, is a popular ayurvedic herb and has been used to treat diabetes, as
      a remedy for cough and as a diuretic. However, very few analytical methods are
      available for quality control of this herb and its marketed formulations.
      OBJECTIVES: To develop and validate a new, rapid, sensitive and selective HPLC
      ESI (electrospray ionisation)-MS/MS method for quantitative estimation of
      gymnemagenin in G. sylvestre and its marketed formulations. METHOD: HPLC-ESI
      MS/MS method using a multiple reactions monitoring mode was used for quantitation
      of gymnemagenin. Separation was carried out on a Luna C-18 column using gradient
      elution of water and methanol (with 0.1% formic acid and 0.3% ammonia). RESULTS:
      The developed method was validated as per International Conference on
      Harmonisation Guideline ICH-Q2B and found to be accurate, precise and linear over
      a relatively wide range of concentrations (5.280-305.920 ng/mL). Gymnemagenin
      contents were found from 0.056 +/- 0.002 to 4.77 +/- 0.59% w/w in G. sylvestre
      and its marketed formulations. CONCLUSION: The method established is simple,
      rapid, with high sample throughput, and can be used as a tool for quality control
      of G. sylvestre and its formulations.

PMID- 22987644
TI  - Cell-specific insulin resistance: implications for atherosclerosis.
AB  - Insulin resistance is increasingly acknowledged as an independent risk factor for
      cardiovascular disease. Despite this, our understanding of the cellular and
      molecular mechanisms that might account for this relationship remain incompletely
      understood. A key challenge has been in distinguishing between a 'whole-body'
      milieu of inflammation and oxidative stress from the ramifications of cell
      specific resistance to insulin. Transgenic models have now begun to explore the
      cellular influences of insulin resistance on vascular biology, with novel
      implications for atherosclerosis across a range of cells including endothelial
      cells, endothelial progenitor cells, vascular smooth muscle cells, macrophages
      and fibroblasts. Emerging data from these models have also begun to challenge
      conventional dogma. In particular, the findings across various cell types are
      disparate with some even implying a protective influence on vascular biology. We
      now review these data, highlighting recent advances in our understanding of
      cellular resistance to insulin as well as those areas where there remains a
      paucity of data.

PMID- 22987645
TI  - Characterization of TALE genes expression during the first lineage segregation in
      mammalian embryos.
AB  - BACKGROUND: Three amino acid loop extension (TALE) homeodomain-containing
      transcription factors are generally recognized for their role in organogenesis
      and differentiation during embryogenesis. However, very little is known about the
      expression and function of Meis, Pbx, and Prep genes during early development.
      RESULTS: In order to determine whether TALE proteins could contribute to the
      early cell fate decisions in mammalian development, this study aimed to
      characterize in a systematic manner the pattern of expression of all Meis, Pbx,
      and Prep genes from the precompaction to blastocyst stage corresponding to the
      first step of cell differentiation in mammals. To reveal to what extent TALE
      genes expression at these early stages is a conserved feature among mammals, this
      study was performed in parallel in the bovine and mouse models. We demonstrated
      the transcription and translation of TALE genes, before gastrulation in the two
      species. At least one member of Meis, Pbx, and Prep subfamilies was found
      expressed at the RNA and protein levels but different patterns of expression were
      observed between genes and between species, suggesting specific gene regulations.
      CONCLUSIONS: Taken together, these results suggest a previously unexpected
      involvement of these factors during the early development in mammals.

PMID- 22987646
TI  - Circularly polarized blue luminescent spherulites consisting of hierarchically
      assembled ionic conjugated polymers with a helically pi-stacked structure.
AB  - Cationic pi-conjugated polymers form an interchain helically pi-stacked assembly
      with anionic chiral compounds that is stabilized by both electrostatic and pi-pi
      interactions to hierarchically self-organize into a spherulite with a circularly
      polarized blue luminescence. To the best of our knowledge, this is the first
      example of a chiroptical spherulite that is hierarchically constructed from pi
      conjugated polymers.

PMID- 22987647
TI  - 30(th)  Cologne workshop on dope analysis (Manfred Donike workshop).

PMID- 22987648
TI  - Self-resistance to an antitumor antibiotic: a DNA glycosylase triggers the base
      excision repair system in yatakemycin biosynthesis.
AB  - Resistance is (not) futile: The yatakemycin biosynthetic gene cluster involves
      the ytkR2 gene, which encodes a protein with homology to a recently discovered
      bacterial DNA glycosylase. Genetic validation in vivo, biochemical assays, and in
      vitro mutagenesis studies revealed that YtkR2 confers resistance for the bacteria
      by specifically recognizing and cleaving the YTM-modified base (see scheme).

PMID- 22987649
TI  - The development of a loop-mediated isothermal amplification method (LAMP) for
      Echinococcus granulosus [corrected] coprodetection.
AB  - We have previously developed a polymerase chain reaction (PCR) assay for
      detection of Echinococcus granulosus infection, which proved very sensitive and
      specific for identification of infected dogs. We have now developed a loop
      mediated isothermal amplification (LAMP) assay, which amplifies the same genomic
      repeated sequences of E. granulosus for coprodetection. This assay enabled
      detection of a single egg in fecal samples and showed high species specificity
      for E. granulosus with no cross-amplification of DNA from closely related
      helminths, including Echinococcus multilocularis. Because the method does not
      require thermocycling for DNA amplification, or electrophoresis for amplicon
      detection, it can potentially be used for premortem identification of E.
      granulosus-infected dogs to enable large-scale surveys in endemic countries where
      highly specialized equipment to undertake PCR analysis is rare.

PMID- 22987650
TI  - Cytokine factors present in dengue patient sera induces alterations of junctional
      proteins in human endothelial cells.
AB  - Plasma leakage in severe dengue has been postulated to be associated with skewed
      cytokine immune responses. In this study, the association of cytokines with
      vascular permeability in dengue patients was investigated. Human serum samples
      collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic
      fever, and 6 healthy) were subjected to cytokines analysis by using Luminex
      Multiplex Technology. Selected serum samples from patients with dengue
      hemorrhagic fever sera and recombinant human cytokines were then tested for roles
      on inducing vascular permeability by treatment of human umbilical vein
      endothelial cells. Confocal immunofluorescence staining indicated morphologic
      alteration of human umbilical vein endothelial cells treated with serum samples
      from patients with dengue hemorrhagic fever compared with serum samples from
      healthy persons. The findings suggest that cytokines produced during dengue
      hemorrhagic infections could induce alterations in the vascular endothelium,
      which may play a fundamental role in the pathophysiology of dengue.

PMID- 22987651
TI  - Schistosoma mansoni morbidity among school-aged children: a SCORE project in
      Kenya.
AB  - Schistosomiasis control programs aim to reduce morbidity but are evaluated by
      infection prevalence and intensity reduction. We present baseline cross-sectional
      data from a nested cohort study comparing indicators of morbidity for measuring
      program impact. Eight hundred twenty-two schoolchildren 7-8 years of age from
      Nyanza Province, Kenya, contributed stool for diagnosis of Schistosoma mansoni
      and soil-transmitted helminths (STH) and blood smears for malaria, and were
      evaluated for anemia, quality of life, exercise tolerance, anthropometry, and
      ultrasound abnormalities. Schistosoma mansoni, STH, and malaria infection
      prevalence were 69%, 25%, and 8%, respectively. Only anemia and S. mansoni
      infection (adjusted odds ratio [aOR] = 1.70; confidence interval [CI] = 1.03
      2.80), and hepatomegaly and heavy S. mansoni infection (aOR = 2.21; CI = 1.19
      4.11) were associated. Though anemia and hepatomegaly appeared most useful at
      baseline, additional morbidity indicators may be sensitive longitudinal measures
      to evaluate schistosomiasis program health impact.

PMID- 22987652
TI  - Development of clinical immunity to malaria in highland areas of low and unstable
      transmission.
AB  - In highland areas of unstable, low malaria transmission, the extent to which
      immunity to uncomplicated malaria develops with age and intermittent parasite
      exposure has not been well characterized. We conducted active surveillance for
      clinical malaria during April 2003-March 2005 in two highland areas of western
      Kenya (Kapsisiywa and Kipsamoite). In both sites, annual malaria incidence was
      significantly lower in persons >= 15 years of age than in persons < 5 years of
      age (Kapsisiywa: incidence = 382.9 cases/1,000 persons among persons < 1-4 years
      of age versus 135.1 cases/1,000 persons among persons >= 15 years of age;
      Kipsamoite: incidence = 233.0 cases/1,000 persons in persons < 1-4 years of age
      versus 43.3 cases/1,000 persons in persons >= 15 years of age). In Kapsisiywa,
      among persons with malaria, parasite density and axillary body temperature were
      also significantly lower in persons >= 15 years of age than in persons < 5 years
      of age. Even in highland areas of unstable and low malaria transmission, age is
      associated with development of clinical immunity to malaria.

PMID- 22987653
TI  - Congenital transmission of Trypanosoma cruzi in non-endemic areas: evaluation of
      a screening program in a tertiary care hospital in Barcelona, Spain.
AB  - The impact of Chagas disease is no longer restricted to endemic areas. The aim of
      this study is to evaluate a 2-year period of a vertical transmission screening
      program of Trypanosoma cruzi infection in a tertiary care hospital in Barcelona
      (Spain). Two enzyme-linked immunosorbent assays (recombinant and crude antigen)
      were performed in parallel to pregnant women at risk of T. cruzi infection.
      Discordant results were confirmed by a third diagnostic test. In the case of a
      positive result, the newborn was tested at birth and after 8 months of life. A
      total of 1,473 women met the inclusion criteria for the screening program with a
      resulting seroprevalence for T. cruzi of 3.5% (2.2-5.2% 95% confidence interval
      [95% CI]). One case of congenital infection was identified. Screening programs
      for vertically transmitted T. cruzi acute infection are beneficial in non-endemic
      areas for early detection and treatment of acute infection.

PMID- 22987654
TI  - Preventing zoonotic canine leishmaniasis in northeastern Brazil: pet attachment
      and adoption of community Leishmania prevention.
AB  - Visceral leishmaniasis (VL), caused by Leishmania infantum chagasi (L.i. chagasi
      syn. infantum) in northeastern Brazil, was responsible for 51,000 new VL cases
      from 1980 to 2003. Household presence of L. infantum-infected dogs is a major
      risk factor for human infection. Despite culling of dogs based on seropositivity,
      canine L. infantum seroprevalence remains near 20%, suggesting that dog culling
      is ineffective for preventing VL spread. We administered a cross-sectional survey
      to 224 households within 300 m of the homes of VL human patients diagnosed within
      the last year. The goal was to develop a model for voluntary preventative use
      based on characteristics and motivations of dog owners. We identified that owner
      knowledge deficiencies regarding canine transmission of L. infantum associated
      with increased risk of dog infection (odds ratio [OR] = 3.681, confidence
      interval [CI] = 1.223, 11.08). Higher owner education was associated with
      decreased levels of dog seropositivity (OR = 0.40, CI = 0.20, 0.81). Pet
      attachment (P = 0.036) and perception of risk/disease knowledge (P = 0.040) were
      significantly associated with willingness to voluntarily purchase canine VL
      prevention. These results highlight the importance of owner attachment to their
      pet in implementing reservoir-targeted zoonotic VL prevention.

PMID- 22987655
TI  - Diphyllobothrium pacificum infection is seldom associated with megaloblastic
      anemia.
AB  - Twenty cases of Dyphillobothrium pacificum (fish tapeworm) infections were
      prospectively studied to determine whether this tapeworm is associated with
      megaloblastic anemia, as commonly reported for D. latum infections. The most
      frequent symptoms were fatigue and mild abdominal pain, which were identified in
      approximately 66.6% of the 18 patients interviewed. Fourteen patients received
      treatment with niclosamide and all were cured. The other six patients
      spontaneously eliminated the tapeworms. One patient, who also had chronic
      diabetes and gastric atrophy, had low vitamin B12 levels and megaloblastic
      anemia. In all other patients, including three other patients with anemia,
      baseline vitamin B12 levels were in the reference range and did not significantly
      change when re-assessed three months later. Unlike D. latum, infection with D.
      pacificum is seldom associated with megaloblastic anemia or vitamin B12 deficit.

PMID- 22987656
TI  - The dengue virus mosquito vector Aedes aegypti at high elevation in Mexico.
AB  - Mexico has cities (e.g., Mexico City and Puebla City) located at elevations >
      2,000 m and above the elevation ceiling below which local climates allow the
      dengue virus mosquito vector Aedes aegypti to proliferate. Climate warming could
      raise this ceiling and place high-elevation cities at risk for dengue virus
      transmission. To assess the elevation ceiling for Ae. aegypti and determine the
      potential for using weather/climate parameters to predict mosquito abundance, we
      surveyed 12 communities along an elevation/climate gradient from Veracruz City
      (sea level) to Puebla City (~2,100 m). Ae. aegypti was commonly encountered up to
      1,700 m and present but rare from 1,700 to 2,130 m. This finding extends the
      known elevation range in Mexico by > 300 m. Mosquito abundance was correlated
      with weather parameters, including temperature indices. Potential larval
      development sites were abundant in Puebla City and other high-elevation
      communities, suggesting that Ae. aegypti could proliferate should the climate
      become warmer.

PMID- 22987657
TI  - Evaluating the sustained health impact of household chlorination of drinking
      water in rural Haiti.
AB  - The Jolivert Safe Water for Families program has sold sodium hypochlorite
      solution (chlorine) and conducted household visits in rural Haiti since 2002. To
      assess the impact of the program on diarrheal disease, in 2010 we conducted a
      survey and water quality testing in 201 program participants and 425 control
      households selected at random. Fifty-six percent of participants (versus 10% of
      controls) had free chlorine residuals between 0.2 and 2.0 mg/L, indicating
      correct water treatment. Using intention-to-treat analysis, we found that
      significantly fewer children < 5 in participant households had an episode of
      diarrhea in the previous 48 hours (32% versus 52%; P < 0.001) with 59% reduced
      odds (odds ratio = 0.41, 95% confidence interval = 0.21-0.79). Treatment-on
      treated estimates of the odds of diarrhea indicated larger program effects for
      participants who met more stringent verifications of participation. Diarrheal
      disease reduction in this long-term program was comparable with that seen in
      short-term randomized, controlled interventions, suggesting that household
      chlorination can be an effective long-term water treatment strategy.

PMID- 22987658
TI  - Mechanism of anemia in Schistosoma mansoni-infected school children in Western
      Kenya.
AB  - A better understanding of the mechanism of anemia associated with Schistosoma
      mansoni infection might provide useful information on how treatment programs are
      implemented to minimize schistosomiasis-associated morbidity and maximize
      treatment impact. We used a cross-sectional study with serum samples from 206
      Kenyan school children to determine the mechanisms in S. mansoni-associated
      anemia. Serum ferritin and soluble transferrin receptor levels were measured by
      using an enzyme-linked immunosorbent assay. Results suggest that S. mansoni
      infected persons are more likely (odds ratio = 3.68, 95% confidence interval =
      1.33-10.1) to have levels of serum ferritin (> 100 ng/mL) that are associated
      with anemia of inflammation (AI) than S. mansoni-uninfected children. Our results
      suggest that AI is the most common form of anemia in S. mansoni infections. In
      contrast, the mechanism of anemia in S. mansoni-uninfected children was iron
      deficiency. Moreover, the prevalence of AI in the study participants demonstrated
      a significant trend with S. mansoni infection intensity (P < 0.001). Our results
      are consistent with those observed in S. japonicum-associated anemia.

PMID- 22987660
TI  - Adaptive prior variance calibration in the Bayesian continual reassessment
      method.
AB  - The use of the continual reassessment method (CRM) and other model-based
      approaches to design Phase I clinical trials has increased owing to the ability
      of the CRM to identify the maximum tolerated dose better than the 3 + 3 method.
      However, the CRM can be sensitive to the variance selected for the prior
      distribution of the model parameter, especially when a small number of patients
      are enrolled. Although methods have emerged to adaptively select skeletons and to
      calibrate the prior variance only at the beginning of a trial, there has not been
      any approach developed to adaptively calibrate the prior variance throughout a
      trial. We propose three systematic approaches to adaptively calibrate the prior
      variance during a trial and compare them via simulation with methods proposed to
      calibrate the variance at the beginning of a trial.

PMID- 22987659
TI  - Focal aberrations indicate EYA2 and hsa-miR-375 as oncogene and tumor suppressor
      in cervical carcinogenesis.
AB  - Cervical cancer results from persistent infection with high-risk human
      papillomavirus (hrHPV). Common genetic aberrations in cervical (pre)cancers
      encompass large genomic regions with numerous genes, hampering identification of
      driver genes. This study aimed to identify genes functionally involved in HPV
      mediated transformation by analysis of focal aberrations (<3 Mb) in high-grade
      cervical intraepithelial neoplasia (hgCIN). Focal chromosomal aberrations were
      determined in high-resolution array comparative genomic hybridization data of 60
      hgCIN. Genes located within focal aberrations were validated using 2 external
      gene expression datasets or qRT-PCR. Functional roles of candidate genes EYA2
      (20q13) and hsa-miR-375 (2q35) were studied by siRNA-mediated knock-down and
      overexpression, respectively, in hrHPV-containing cell lines. We identified 74
      focal aberrations encoding 305 genes. Concurrent altered expression in hgCIN
      and/or cervical carcinomas compared with normal cervical samples was shown for
      ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2, and NCR2. Gene silencing of
      EYA2 significantly reduced viability, migratory capacity, and anchorage
      independent growth of HPV16-transformed keratinocytes. For hsa-miR-375, a direct
      correlation between a (focal) loss and significantly reduced expression was
      found. Downregulation of hsa-miR-375 expression was confirmed in an independent
      series of cervical tissues. Ectopic expression of hsa-miR-375 in 2 cervical
      carcinoma cell lines reduced cellular viability. Our data provide a proof of
      concept that chromosomal aberrations are actively contributing to HPV-induced
      carcinogenesis and identify EYA2 and hsa-miR-375 as oncogene and tumor suppressor
      gene, respectively.

PMID- 22987662
TI  - Atypical findings in three patients with Pai syndrome and literature review.
AB  - Pai syndrome is a rare disorder characterized by congenital nasal or facial
      polyp, midline cleft lip, pericallosal lipoma, ocular anomalies, and normal
      neuropsychological development. Here, we report on three patients with Pai
      syndrome and atypical findings: temporal triangular alopecia, posterior
      lenticonus, bilateral palatal pits, bifid uvula, hypospadias, sacral dimple, true
      tracheal bronchus, and epilepsy. Thirty-three cases of Pai syndrome have been
      described so far. We present a review of the previously reported cases and
      suggest modified diagnostic criteria for Pai syndrome.

PMID- 22987661
TI  - Diffusion tensor imaging based network analysis detects alterations of
      neuroconnectivity in patients with clinically early relapsing-remitting multiple
      sclerosis.
AB  - Although it is inarguable that conventional MRI (cMRI) has greatly contributed to
      the diagnosis and assessment of multiple sclerosis (MS), cMRI does not show close
      correlation with clinical findings or pathologic features, and is unable to
      predict prognosis or stratify disease severity. To this end, diffusion tensor
      imaging (DTI) with tractography and neuroconnectivity analysis may assist disease
      assessment in MS. We, therefore, attempted this pilot study for initial
      assessment of early relapsing-remitting MS (RRMS). Neuroconnectivity analysis was
      used for evaluation of 24 early RRMS patients within 2 years of presentation, and
      compared to the network measures of a group of 30 age-and-gender-matched normal
      control subjects. To account for the situation that the connections between two
      adjacent regions may be disrupted by an MS lesion, a new metric, network
      communicability, was adopted to measure both direct and indirect connections. For
      each anatomical area, the brain network communicability and average path length
      were computed and compared to characterize the network changes in efficiencies.
      Statistically significant (P < 0.05) loss of communicability was revealed in our
      RRMS cohort, particularly in the frontal and hippocampal/parahippocampal regions
      as well as the motor strip and occipital lobes. Correlation with the 25-foot Walk
      test with communicability measures in the left superior frontal (r = -0.71) as
      well as the left superior temporal gyrus (r = -0.43) and left postcentral gyrus
      (r = -0.41) were identified. Additionally identified were increased
      communicability between the deep gray matter structures (left thalamus and
      putamen) with the major interhemispheric and intrahemispheric white matter
      tracts, the corpus callosum, and cingulum, respectively. These foci of increased
      communicability are thought to represent compensatory changes. The proposed DTI
      based neuroconnectivity analysis demonstrated quantifiable, structurally relevant
      alterations of fiber tract connections in early RRMS and paves the way for
      longitudinal studies in larger patient groups.

PMID- 22987663
TI  - Optimizing the fat and water content of impaction bone allograft.
AB  - Fresh morselized impacted bone graft usually fails due to shear forces. The
      presence of fat, water, and marrow particles act as interparticle lubricants,
      reducing the interlocking of particles and allowing the graft to move more
      freely. Furthermore, the presence of this incompressible fluid damps and resists
      compressive forces during impaction, preventing the graft particles from moving
      into a closer formation. We believe there exists an ideal concentration of fat
      and water that will maximize resistance to shear forces. We performed mechanical
      shear testing in vitro on morselized human femoral heads, varying the amount of
      fat and water to determine their optimum concentrations. Level of fat and water
      were determined that increased strength by 36% over unaltered bone graft. This is
      most closely approximated in an operating room by washing and subsequently
      squeezing the bone graft. Optimizing the fat and water content of bone graft
      produces a stronger graft that is more resistant to shear stresses, protecting
      the surgical construct until bone growth can occur.

PMID- 22987664
TI  - Coupling of a high-resolution monoamine oxidase-A inhibitor assay and HPLC-SPE
      NMR for advanced bioactivity profiling of plant extracts.
AB  - INTRODUCTION: Depression is a mental disease causing large personal and socio
      economic problems, and new improved drugs are therefore needed. Selective
      monoamine oxidase A (MAO-A) inhibitors are potential anti-depressants, but
      discovering new MAO-A inhibitors from natural sources by bioassay-guided
      approaches are a lengthy and time-consuming process. New analytical technologies
      that allow simultaneously chemical and biological screening of extracts are
      therefore urgently needed. METHOD: In the present study we describe coupling of a
      photometric microplate-based high-resolution MAO-A inhibitor assay with a
      hyphenated system consisting of high-performance liquid chromatography, solid
      phase extraction and tube transfer nuclear magnetic resonance (HPLC-SPE-ttNMR).
      The standard compound clorgyline, and an extract of black pepper (Piper nigrum
      L.), representing a complex plant matrix, were used for proof-of-concept.
      RESULTS: The work with clorgyline showed that the microplate-based high
      resolution assay produced MAO-A inhibition profiles that easily allowed detection
      of submicrogram amounts of this selective MAO-A inhibitor. Furthermore, the HPLC
      SPE-ttNMR/high-resolution MAO-A inhibition assay platform allowed identification
      of piperine and two piperine analogues as the main MAO-A inhibitors in the black
      pepper petroleum ether extract. CONCLUSION: The HPLC-SPE-ttNMR/high-resolution
      MAO-A inhibition assay platform is a powerful tool for fast and efficient
      identification of new MAO-A inhibitors from complex extracts, and promise future
      advancement in the search for new anti-depressants from natural sources.

PMID- 22987665
TI  - Equilibrium vitrification of mouse embryos at various developmental stages.
AB  - Previously, we developed a new method by which 2-cell mouse embryos can be
      vitrified in liquid nitrogen in a near-equilibrium state, and then kept at -80
      degrees C for several days. In the present study, we examined whether or not the
      method was effective for mouse embryos at other developmental stages. Eight-cell
      embryos, morulae, and expanded blastocysts of ICR mice were vitrified with
      ethylene glycol-based solutions, named EFSc because of their composition of
      ethylene glycol (30-40%, v/v) and FSc solution. The FSc solution was PB1 medium
      containing 30% (w/v) Ficoll PM-70 plus 1.5 M sucrose. The extent of equilibrium
      was assessed by examining how well vitrified embryos survived after being kept at
      -80 degrees C. When 8-cell embryos and morulae were vitrified with EFS35c or
      EFS40c and then kept at -80 degrees C, the survival rate was high even after 4
      days in storage and remained high after re-cooling in liquid nitrogen. On the
      other hand, the survival of vitrified-expanded blastocysts kept at -80 degrees C
      was low. Therefore, 8-cell embryos and morulae can be vitrified in a near
      equilibrium state using the same method as for 2-cell embryos. A high proportion
      of C57BL/6J embryos at the 2-cell, 8-cell, and morula stages vitrified with
      EFS35c developed to term after transportation on dry ice, re-cooling in liquid
      nitrogen, and transfer to recipients. In conclusion, the near-equilibrium
      vitrification method, which is effective for 2-cell mouse embryos, is also
      effective for embryos at the 8-cell and morula stages. The method would enable
      handy transportation of vitrified embryos using dry ice.

PMID- 22987667
TI  - Modeling zero-inflated count data using a covariate-dependent random effect
      model.
AB  - In various medical related researches, excessive zeros, which make the standard
      Poisson regression model inadequate, often exist in count data. We proposed a
      covariate-dependent random effect model to accommodate the excess zeros and the
      heterogeneity in the population simultaneously. This work is motivated by a data
      set from a survey on the dental health status of Hong Kong preschool children
      where the response variable is the number of decayed, missing, or filled teeth.
      The random effect has a sound biological interpretation as the overall oral
      health status or other personal qualities of an individual child that is
      unobserved and unable to be quantified easily. The overall measure of oral health
      status, responsible for accommodating the excessive zeros and also the
      heterogeneity among the children, is covariate dependent. This covariate
      dependent random effect model allows one to distinguish whether a potential
      covariate has an effect on the conceived overall oral health condition of the
      children, that is, the random effect, or has a direct effect on the magnitude of
      the counts, or both. We proposed a multiple imputation approach for estimation of
      the parameters. We discussed the choice of the imputation size. We evaluated the
      performance of the proposed estimation method through simulation studies, and we
      applied the model and method to the dental data.

PMID- 22987666
TI  - Computational analysis and characterization of UCE-like elements (ULEs) in plant
      genomes.
AB  - Ultraconserved elements (UCEs), stretches of DNA that are identical between
      distantly related species, are enigmatic genomic features whose function is not
      well understood. First identified and characterized in mammals, UCEs have been
      proposed to play important roles in gene regulation, RNA processing, and
      maintaining genome integrity. However, because all of these functions can
      tolerate some sequence variation, their ultraconserved and ultraselected nature
      is not explained. We investigated whether there are highly conserved DNA elements
      without genic function in distantly related plant genomes. We compared the
      genomes of Arabidopsis thaliana and Vitis vinifera; species that diverged ~115
      million years ago (Mya). We identified 36 highly conserved elements with at least
      85% similarity that are longer than 55 bp. Interestingly, these elements exhibit
      properties similar to mammalian UCEs, such that we named them UCE-like elements
      (ULEs). ULEs are located in intergenic or intronic regions and are depleted from
      segmental duplications. Like UCEs, ULEs are under strong purifying selection,
      suggesting a functional role for these elements. As their mammalian counterparts,
      ULEs show a sharp drop of A+T content at their borders and are enriched close to
      genes encoding transcription factors and genes involved in development, the
      latter showing preferential expression in undifferentiated tissues. By comparing
      the genomes of Brachypodium distachyon and Oryza sativa, species that diverged
      ~50 Mya, we identified a different set of ULEs with similar properties in
      monocots. The identification of ULEs in plant genomes offers new opportunities to
      study their possible roles in genome function, integrity, and regulation.

PMID- 22987669
TI  - Inter-laboratory assessment of flow cytometric monocyte HLA-DR expression in
      clinical samples.
AB  - BACKGROUND: Diminished expression of human leukocyte antigen DR on circulating
      monocytes (mHLA-DR) is a reliable indicator of immunosuppression in critically
      ill patients, predictive of both adverse outcome and septic complications. The
      objective of the present work was to test, in an inter-laboratory clinical study,
      a standardized protocol for mHLA-DR measurement by flow cytometry. METHODS: mHLA
      DR was assessed in fresh whole blood according to a standardized staining
      protocol. Cells were analyzed on different flow cytometers (FC500, Navios, FACS
      Canto II) in different laboratories (Lyon and Grenoble). Results were expressed
      as numbers of antibodies bound per cell (AB/C). RESULTS: Correlations between
      results were excellent (Pearson and interclass correlation coefficients > 0.98).
      Coefficients of variations for intra-assay precision ranged from 1.9 to 3.2%.
      CONCLUSION: The present report highlights the robustness of this standardized
      flow cytometric protocol for mHLA-DR measurement in multicentric clinical
      studies.

PMID- 22987670
TI  - Altered resting-state activity in seasonal affective disorder.
AB  - At present, our knowledge about seasonal affective disorder (SAD) is based mainly
      up on clinical symptoms, epidemiology, behavioral characteristics and light
      therapy. Recently developed measures of resting-state functional brain activity
      might provide neurobiological markers of brain disorders. Studying functional
      brain activity in SAD could enhance our understanding of its nature and possible
      treatment strategies. Functional network connectivity (measured using ICA-dual
      regression), and amplitude of low-frequency fluctuations (ALFF) were measured in
      45 antidepressant-free patients (39.78 +/- 10.64, 30 ?, 15 ?) diagnosed with SAD
      and compared with age-, gender- and ethnicity-matched healthy controls (HCs)
      using resting-state functional magnetic resonance imaging. After correcting for
      Type 1 error at high model orders (inter-RSN correction), SAD patients showed
      significantly increased functional connectivity in 11 of the 47 identified RSNs.
      Increased functional connectivity involved RSNs such as visual, sensorimotor, and
      attentional networks. Moreover, our results revealed that SAD patients compared
      with HCs showed significant higher ALFF in the visual and right sensorimotor
      cortex. Abnormally altered functional activity detected in SAD supports
      previously reported attentional and psychomotor symptoms in patients suffering
      from SAD. Further studies, particularly under task conditions, are needed in
      order to specifically investigate cognitive deficits in SAD.

PMID- 22987671
TI  - Highly enantioselective transfer hydrogenation of quinolines catalyzed by gold
      phosphates: achiral ligand tuning and chiral-anion control of stereoselectivity.
AB  - A little gold goes a long way: as little as 0.01 mol % of chiral gold phosphate
      is sufficient to afford the asymmetric transfer hydrogenation of quinolines with
      high stereoselectivity (up to 98 % ee). The achiral ligands on gold were found to
      have considerable effect on the catalytic efficiency.

PMID- 22987672
TI  - Meconium testing for fatty acid ethyl esters: a 2011 status report.
AB  - The Canadian Association of Pediatric Health Centres, working in partnership with
      the Public Health Agency of Canada has recently published a toolkit to guide
      screening for identification of risk of FAS/FASD. One of the tools highlighted is
      the testing of meconium for fatty acid ethyl esters to identify high risk
      pregnancies and to support associated prevention programs. This paper describes
      the conclusions of a workshop held in Prince Edward Island in September 2011 to
      discuss key issues surrounding the wider deployment of meconium testing for
      assessment of population risk for FAS/FASD.

PMID- 22987674
TI  - Computational models of perirhinal cortex function.
AB  - I review seven models of the contribution of perirhinal cortex (PRC) or
      neighboring neocortical regions to cognition. Five of the models address
      recognition memory function (Sohal and Hasselmo (2000) Network 11:169-190; Bogacz
      et al. (2001) J Comput Neurosci 10:5-23; Bogacz and Brown (2003a) Neurocomputing
      52:1-6; Norman and O'Reilly (2003) Psychol Rev 110:611-646; Cowell et al. (2006)
      J Neurosci 26:12186-12197) and two account for the role of PRC in visual
      discrimination learning (Bussey and Saksida (2002) Eur J Neurosci 15:355-364;
      Cowell et al. (2010b) J Cogn Neurosci 22:2460-2479). The models span a range of
      biological scales and target a variety of datasets, such that like for like
      comparison between them is not always possible. I lay out a novel framework for
      facilitating comparison by defining some general abstract principles concerning
      the organization of cognition in the brain about which all of the models make a
      statement. The controversies that are revealed by scrutinizing the models within
      this framework highlight the fundamental questions that remain to be answered by
      future research. Ultimately, it is by combining these disparate accounts to build
      a unified model that bridges several levels of biological scale and accounts for
      multiple psychological phenomena that a full account of PRC function will be
      achieved.

PMID- 22987673
TI  - Why is there a special issue on perirhinal cortex in a journal called
      hippocampus? The perirhinal cortex in historical perspective.
AB  - Despite its small size, the perirhinal cortex (PRh) plays a central role in
      understanding the cerebral cortex, vision, and memory; it figures in discussions
      of cognitive capacities as diverse as object perception, semantic knowledge,
      feelings of familiarity, and conscious recollection. Two conceptual constructs
      have encompassed PRh. The current orthodoxy incorporates PRh within the medial
      temporal lobe (MTL) as a memory area; an alternative considers PRh to be a
      sensory area with a role in both perception and memory. A historical perspective
      provides insight into both these ideas. PRh came to be included in the MTL
      because of two accidents of history. In evolutionary history, the hippocampus
      migrated from its ancestral situation as medial cortex into the temporal lobe; in
      the history of neuropsychology, a "memory system" that originally consisted of
      the amygdala and hippocampus came to include PRh. These two histories explain why
      a part of the sensory neocortex, PRh, entered into the conceptual construct
      called the MTL. They also explain why some experimental results seem to exclude a
      perceptual function for this sensory area, while others embrace perception. The
      exclusion of perceptual functions results from a history of categorizing tasks as
      perceptual or mnemonic, often on inadequate grounds. By exploring the role of PRh
      in encoding, representing, and retrieving stimulus information, it can be
      understood as a part of the sensory neocortex, one that has the same relationship
      with the hippocampus as do other parts of the neocortex that evolved at about the
      same time.

PMID- 22987675
TI  - The perirhinal cortex modulates V2 activity in response to the agreement between
      part familiarity and configuration familiarity.
AB  - Research has demonstrated that the perirhinal cortex (PRC) represents complex
      object-level feature configurations, and participates in familiarity versus
      novelty discrimination. Barense et al. [(in press) Cerebral Cortex, 22:11,
      doi:10.1093/cercor/bhr347] postulated that, in addition, the PRC modulates part
      familiarity responses in lower-level visual areas. We used fMRI to measure
      activation in the PRC and V2 in response to silhouettes presented peripherally
      while participants maintained central fixation and performed an object
      recognition task. There were three types of silhouettes: Familiar Configurations
      portrayed real-world objects; Part-Rearranged Novel Configurations created by
      spatially rearranging the parts of the familiar configurations; and Control Novel
      Configurations in which both the configuration and the ensemble of parts
      comprising it were novel. For right visual field (RVF) presentation, BOLD
      responses revealed a significant linear trend in bilateral BA 35 of the PRC
      (highest activation for Familiar Configurations, lowest for Part-Rearranged Novel
      Configurations, with Control Novel Configurations in between). For left visual
      field (LVF) presentation, a significant linear trend was found in a different
      area (bilateral BA 38, temporal pole) in the opposite direction (Part-Rearranged
      Novel Configurations highest, Familiar Configurations lowest). These data confirm
      that the PRC is sensitive to the agreement in familiarity between the
      configuration level and the part level. As predicted, V2 activation mimicked that
      of the PRC: for RVF presentation, activity in V2 was significantly higher in the
      left hemisphere for Familiar Configurations than for Part-Rearranged Novel
      Configurations, and for LVF presentation, the opposite effect was found in right
      hemisphere V2. We attribute these patterns in V2 to feedback from the PRC because
      receptive fields in V2 encompass parts but not configurations. These results
      reveal two new aspects of PRC function: (1) it is sensitive to the congruency
      between the familiarity of object configurations and the parts comprising those
      configurations and (2) it likely modulates familiarity responses in visual area
      V2.

PMID- 22987677
TI  - Reducing perceptual interference improves visual discrimination in mild cognitive
      impairment: implications for a model of perirhinal cortex function.
AB  - Memory loss resulting from damage to the medial temporal lobes (MTL) is
      traditionally considered to reflect damage to a dedicated, exclusive memory
      system. Recent work, however, has suggested that damage to one MTL structure, the
      perirhinal cortex (PRC), compromises complex object representations that are
      necessary for both memory and perception. These representations are thought to be
      critical in shielding against the interference caused by a stream of visually
      similar input. In this study, we administered a complex object discrimination
      task to two memory-impaired populations thought to have brain damage that
      includes the PRC [patients diagnosed with amnestic mild cognitive impairment
      (MCI), and older adults at risk for MCI], as well as age-matched controls.
      Importantly, we carefully manipulated the level of interference: in the High
      Interference condition, participants completed a block of consecutive
      perceptually similar complex object discriminations, whereas in the Low
      Interference condition, we interspersed perceptually dissimilar objects such that
      there was less buildup of visual interference. We found that both memory-impaired
      populations were impaired on the High Interference condition compared with
      controls, but critically, by reducing the degree of perceptual interference, we
      were largely able to improve their performance. These findings, when taken
      together with convergent evidence from animals with selective PRC lesions and
      amnesic patients with focal damage to the PRC, provide support for a
      representational-hierarchical model of PRC function and suggest that memory loss
      following PRC damage may reflect a heightened vulnerability to perceptual
      interference.

PMID- 22987676
TI  - Age-related impairment in a complex object discrimination task that engages
      perirhinal cortex.
AB  - Previous lesion studies have shown compromised complex object discrimination in
      rats, monkeys, and human patients with damage to the perirhinal cortical region
      (PRC) of the medial temporal lobe. These findings support the notion that the PRC
      is involved in object discrimination when pairs of objects have a high degree of
      overlapping features but not when object discrimination can be resolved on the
      basis of a single feature (e.g., size or color). Recent studies have demonstrated
      age-related functional changes to the PRC in animals (rats and monkeys) resulting
      in impaired complex object discrimination and object recognition. To date, no
      studies have compared younger and older humans using paradigms previously shown
      to engage the PRC. To investigate the influence of age on complex object
      discrimination in humans, the present study used an object matching paradigm for
      blob-like objects that have previously been shown to recruit the PRC. Difficulty
      was manipulated by varying the number of overlapping features between objects.
      Functional MRI data was acquired to determine the involvement of the PRC in the
      two groups during complex object discrimination. Results indicated that while
      young and older adults performed similarly on the easy version of the task, most
      older adults were impaired relative to young participants when the number of
      overlapping features increased. fMRI results suggest that older adults do not
      engage bilateral anterior PRC to the same extent as young adults. Specifically,
      complex object matching performance in older adults was predicted by the degree
      to which they engage left anterior PRC. These results provide evidence for human
      age-related changes in PRC function that impact complex object discrimination.

PMID- 22987679
TI  - Recognition memory and synaptic plasticity in the perirhinal and prefrontal
      cortices.
AB  - Work is reviewed that relates recognition memory to studies of synaptic
      plasticity mechanisms in perirhinal and prefrontal cortices. The aim is to
      consider evidence that perirhinal cortex and medial prefrontal cortex store
      rather than merely transmit information necessary for recognition memory and, if
      so, to consider what mechanisms are potentially available within these cortices
      for producing such storage through synaptic change. Interventions with known
      actions on plasticity mechanisms are reviewed in relation to their effects on
      recognition memory processes. These interventions importantly include those
      involving antagonism of glutamatergic and cholinergic receptors but also
      inhibition of plasticity consolidation and expression mechanisms. It is concluded
      that there is strong evidence that perirhinal cortex is involved in information
      storage necessary for object recognition memory and, moreover, that such storage
      involves synaptic weakening mechanisms including the removal of AMPA glutamate
      receptors from synapses. There is good evidence that medial prefrontal cortex is
      necessary for associative and temporal order recognition memory and that this
      cortex expresses plasticity mechanisms that potentially allow the storage of
      information. However, the case for medial prefrontal cortex acting as a store
      requires further support.

PMID- 22987678
TI  - Differential effects of experience on tuning properties of macaque MTL neurons in
      a passive viewing task.
AB  - The structures of the medial temporal lobe (MTL) have been shown to be causally
      involved in episodic and recognition memory. However, recent work in a number of
      species has demonstrated that impairments in recognition memory seen following
      lesions of the perirhinal cortex (PRh) can be accounted for by deficits in
      perceptual discrimination. These findings suggest that object representation,
      rather than explicit recognition memory signals, may be crucial to the mnemonic
      process. Given the large amount of visual information encountered by primates,
      there must be a reconsideration of the mechanisms by which the brain efficiently
      stores visually presented information. Previous neurophysiological recordings
      from MTL structures in primates have largely focused on tasks that implicitly
      define object familiarity (i.e., novel vs. familiar) or contain significant
      mnemonic demands (e.g., conditional associations between two stimuli), limiting
      their utility in understanding the mechanisms underlying visual object
      recognition and information storage. To clarify how different regions in the MTL
      may contribute to visual recognition, we recorded from three rhesus macaques
      performing a passive viewing task. The task design systematically varies the
      relative familiarity of different stimuli enabling an examination of how neural
      activity changes as a function of experience. The data collected during this
      passive viewing task revealed that neurons in the MTL are generally not sensitive
      to the relative familiarity of a stimulus. In addition, when the specificity
      (i.e., which images a neuron was selective for) of individual neurons was
      analyzed, there was a significant dissociation between different medial temporal
      regions, with only neurons in TF, but not CA3 or the PRh, altering their activity
      as stimuli became familiar. The implications of these findings are discussed in
      the context of how MTL structures process information during a passive viewing
      paradigm.

PMID- 22987680
TI  - Representation of three-dimensional objects by the rat perirhinal cortex.
AB  - The perirhinal cortex (PRC) is known to play an important role in object
      recognition. Little is known, however, regarding the activity of PRC neurons
      during the presentation of stimuli that are commonly used for recognition memory
      tasks in rodents, that is, three-dimensional objects. Rats in the present study
      were exposed to three-dimensional objects while they traversed a circular track
      for food reward. Under some behavioral conditions, the track contained novel
      objects, familiar objects, or no objects. Approximately 38% of PRC neurons
      demonstrated "object fields" (a selective increase in firing at the location of
      one or more objects). Although the rats spent more time exploring the objects
      when they were novel compared to familiar, indicating successful recognition
      memory, the proportion of object fields and the firing rates of PRC neurons were
      not affected by the rats' previous experience with the objects. Together, these
      data indicate that the activity of PRC cells is powerfully affected by the
      presence of objects while animals navigate through an environment; but under
      these conditions, the firing patterns are not altered by the relative novelty of
      objects during successful object recognition.

PMID- 22987681
TI  - Perirhinal cortex represents nonspatial, but not spatial, information in rats
      foraging in the presence of objects: comparison with lateral entorhinal cortex.
AB  - The medial temporal lobe (MTL) is involved in mnemonic processing. The perirhinal
      cortex (PRC) plays a role in object recognition memory, while the hippocampus is
      required for certain forms of spatial memory and episodic memory. The lateral
      entorhinal cortex (LEC) receives direct projections from PRC and is one of the
      two major cortical inputs to the hippocampus. The transformations that occur
      between PRC and LEC neural representations are not well understood. Here, we show
      that PRC and LEC had similarly high proportions of neurons with object-related
      activity (PRC 52/94; LEC 72/153), as expected from their locations in the "what"
      pathway into the hippocampus. However, LEC unit activity showed more spatial
      stability than PRC unit activity. A minority of LEC neurons showed stable spatial
      firing fields away from objects; these firing fields strongly resembled
      hippocampal place fields. None of the PRC neurons showed this place-like firing.
      None of the PRC or LEC neurons demonstrated the high firing rates associated with
      interneurons in hippocampus or medial entorhinal cortex, further dissociating
      this information processing stream from the path-integration based, movement
      related processing of the medial entorhinal cortex and hippocampus. These results
      provide evidence for nonspatial information processing in the PRC-LEC pathway, as
      well as showing a functional dissociation between PRC and LEC, with more purely
      nonspatial representations in PRC and combined spatial-nonspatial representations
      in LEC.

PMID- 22987682
TI  - The effects of combined perirhinal and postrhinal damage on complex
      discrimination tasks.
AB  - Rats with combined lesions of the perirhinal (PER) and postrhinal (POR) cortices
      were trained on a complex discrimination in the simultaneous feature-positive and
      feature-negative discrimination task. In this task, a panel light (L) paired with
      an auditory stimulus determined whether a tone (T) or white noise (N) would be
      rewarded (+) or not rewarded (-). Thus, the light feature determined whether the
      target auditory stimuli were rewarded or not. In each session, trial types were
      LT+, T-, N+, and LN-. We had hypothesized that damage to the target regions would
      impair performance on this task. Acquisition was altered in the lesioned rats,
      but not in the predicted direction. Instead, lesioned rats exhibited
      significantly enhanced acquisition of the discrimination. Manipulation of
      intertrial intervals indicated that reduction of proactive interference did not
      explain the enhancement. Lesioned rats were not different from controls on a
      multiple-cued interval timing task, providing evidence that the enhancement does
      not extend to all types of discriminations and is not due to a deficit in timing.
      Other research shows that rats with PER lesions are impaired on similar tasks,
      thus the enhancement is likely due to the effects of POR damage. Normally in this
      task, context is thought to accrue inhibitory control over other cues. Without
      this inhibitory control, animals might be expected to learn the task more
      efficiently. Our conclusion is that deficits in processing contextual information
      underlie the enhanced acquisition observed in rats with combined PER and POR
      damage on this complex discrimination task.

PMID- 22987683
TI  - Layer V perirhinal cortical ensemble activity during object exploration: a
      comparison between young and aged rats.
AB  - Object recognition memory requires the perirhinal cortex (PRC) and this cognitive
      function declines during normal aging. Recent electrophysiological recordings
      from young rats have shown that neurons in Layer V of the PRC are activated by
      three-dimensional objects. Thus, it is possible that age-related object
      recognition deficits result from alterations in PRC neuron activity in older
      animals. To examine this, the present study used cellular compartment analysis of
      temporal activity by fluorescence in situ hybridization (catFISH) with confocal
      microscopy to monitor cellular distributions of activity-induced Arc RNA in layer
      V of the PRC. Activity was monitored during two distinct epochs of object
      exploration. In one group of rats (6 young/6 aged) animals were placed in a
      familiar testing arena and allowed to explore five different three-dimensional
      objects for two 5-min sessions separated by a 20-min rest (AA). The second group
      of animals (6 young/6 aged) also explored the same objects for two 5-min
      sessions, but the environment was changed between the first and the second epoch
      (AB). Behavioral data showed that both age groups spent less time exploring
      objects during the second epoch, even when the environment changed, indicating
      successful recognition. Although the proportion of active neurons between epochs
      did not change in the AA group, in the AB group more neurons were active during
      epoch 2 of object exploration. This recruitment of neurons into the active neural
      ensemble could serve to signal that familiar stimuli are being encountered in a
      new context. When numbers of Arc positive neurons were compared between age
      groups, the old rats had significantly lower proportions of Arc-positive PRC
      neurons in both the AA and AB behavioral conditions. These data support the
      hypothesis that age-associated functional alterations in the PRC contribute to
      declines in stimulus recognition over the lifespan.

PMID- 22987684
TI  - Grange syndrome: an identifiable cause of stroke in young adults.
AB  - Grange syndrome is a disorder characterized by arterial occlusive disease,
      hypertension, congenital cardiac defects, bone fragility, brachysyndactyly, and
      learning disabilities. It was first described in four members of the same family
      and in two sporadic cases thereafter, suggesting the possibility of various
      patterns of inheritance. We report on the case of an 18-year-old female
      presenting with subarachnoid hemorrhage due to the rupture of a basilar artery
      aneurysm, and with distinctive systemic features including extensive
      vasculopathy, facial dysmorphisms and brachysyndactyly, consistent with the
      diagnosis of Grange syndrome. Although rare and not fully characterized, Grange
      syndrome should be included in the differential diagnosis of stroke at young age.

PMID- 22987685
TI  - Coarse-grained and all-atom modeling of structural states and transitions in
      hemoglobin.
AB  - Hemoglobin (Hb), an oxygen-binding protein composed of four subunits (alpha1,
      alpha2, beta1, and beta2), is a well-known example of allosteric proteins that
      are capable of cooperative ligand binding. Despite decades of studies, the
      structural basis of its cooperativity remains controversial. In this study, we
      have integrated coarse-grained (CG) modeling, all-atom simulation, and structural
      data from X-ray crystallography and wide-angle X-ray scattering (WAXS), aiming to
      probe dynamic properties of the two structural states of Hb (T and R state) and
      the transitions between them. First, by analyzing the WAXS data of unliganded and
      liganded Hb, we have found that the structural ensemble of T or R state is
      dominated by one crystal structure of Hb with small contributions from other
      crystal structures of Hb. Second, we have used normal mode analysis to identify
      two distinct quaternary rotations between the alpha1beta1 and alpha2beta2 dimer,
      which drive the transitions between T and R state. We have also identified the
      hot-spot residues whose mutations are predicted to greatly change these
      quaternary motions. Third, we have generated a CG transition pathway between T
      and R state, which predicts a clear order of quaternary and tertiary changes
      involving alpha and beta subunits in Hb. Fourth, we have used the accelerated
      molecular dynamics to perform an all-atom simulation starting from the T state of
      Hb, and we have observed a transition toward the R state of Hb. Further analysis
      of crystal structural data and the all-atom simulation trajectory has
      corroborated the order of quaternary and tertiary changes predicted by CG
      modeling.

PMID- 22987686
TI  - Magnetic resonance imaging of muscle disease: a pattern-based approach.
AB  - Magnetic resonance imaging (MRI) is a powerful tool to assess the severity,
      distribution, and progression of muscle injury and disease. However, a muscle's
      response to a pathological insult is limited to only a few patterns on MRI, and
      findings can be nonspecific. A pattern-based approach is therefore essential to
      correctly interpret MR studies of abnormal muscle. In this article we review the
      anatomy, function, and normal MRI appearance of skeletal muscle. We present a
      classification scheme that categorizes abnormal MR appearances of muscle into 4
      main pattern descriptors: (1) distribution; (2) change in size and shape; (3) T1
      signal; and (4) T2 signal. Each category is further subdivided into the various
      patterns seen on MRI. Such an approach allows one to systematically assess
      abnormal findings on muscle MRI studies and ascertain clues to the diagnosis or
      differential diagnosis, particularly when findings are correlated with the
      clinical context.

PMID- 22987688
TI  - Dysphagia in Duchenne muscular dystrophy versus myotonic dystrophy type 1.
AB  - INTRODUCTION: In this study we aimed to demonstrate the distinctive features of
      dysphagia in patients with myotonic dystrophy type 1 (DM1) and Duchenne muscular
      dystrophy (DMD). METHODS: Diet-type score (DTS) and maximum tongue pressure (MTP)
      were measured in 20 DM1 and 24 DMD patients; all patients were also examined by
      videofluoroscopy (VF). We used VF to measure the range of hyoid bone excursion
      (RHBE) during pharyngeal transit time and the area of pharyngeal residue (APR)
      after the first swallow. RESULTS: RHBE and APR values for DM1 patients were
      significantly greater than those for DMD patients. DTS and MTP did not differ
      between patients. A significant correlation was observed between DTS, MTP, and
      RHBE in DMD patients, but not in DM1 patients. CONCLUSIONS: Our findings reveal
      the differences in the distinctive features of dysphagia in DM1 and DMD.
      Adjustments in the diet of DMD patients in accordance with swallowing ability
      could be useful.

PMID- 22987689
TI  - Medical costs and health-care resource use in patients with inflammatory
      myopathies in an insured population.
AB  - INTRODUCTION: In this study we determined the health-care costs and resource
      utilization associated with idiopathic inflammatory myopathies (IIMs) in a large
      managed care plan in the USA. METHODS: Myositis subjects >=18 years of age with
      claims-based evidence of IIMs were identified from a health plan database.
      Subjects were matched with unaffected controls, and costs and resource use were
      determined during a 12-month period. RESULTS: A total of 1781 newly diagnosed IIM
      subjects were matched to 5343 controls, and 2697 subjects with existing disease
      were matched to 8091 controls. Mean overall annual medical costs were higher
      among newly diagnosed subjects ($16,319 vs. $4926, P < 0.001) and subjects with
      an existing IIM ($15,539 vs. $5210, P < 0.001) in comparison to controls. IIM
      subjects had significantly higher mean counts of ambulatory visits, specialist
      visits, and inpatient hospital stays compared with controls (all P < 0.001).
      CONCLUSION: Our analysis suggests that IIMs have increased medical costs and
      resource use.

PMID- 22987687
TI  - A quantitative measure of handgrip myotonia in non-dystrophic myotonia.
AB  - INTRODUCTION: Non-dystrophic myotonia (NDM) is characterized by myotonia without
      muscle wasting. A standardized quantitative myotonia assessment (QMA) is
      important for clinical trials. METHODS: Myotonia was assessed in 91 individuals
      enrolled in a natural history study using a commercially available computerized
      handgrip myometer and automated software. Average peak force and 90% to 5%
      relaxation times were compared with historical normal controls studied with
      identical methods. RESULTS: Thirty subjects had chloride channel mutations, 31
      had sodium channel mutations, 6 had DM2 mutations, and 24 had no identified
      mutation. Chloride channel mutations were associated with prolonged first
      handgrip relaxation times and warm-up on subsequent handgrips. Sodium channel
      mutations were associated with prolonged first handgrip relaxation times and
      paradoxical myotonia or warm-up, depending on underlying mutations. DM2 subjects
      had normal relaxation times but decreased peak force. Sample size estimates are
      provided for clinical trial planning. CONCLUSION: QMA is an automated, non
      invasive technique for evaluating myotonia in NDM.

PMID- 22987690
TI  - Comparison of analysis approaches for phase III clinical trials in amyotrophic
      lateral sclerosis.
AB  - INTRODUCTION: In this study we explore several methods for incorporating survival
      information in the analysis of Amyotrophic Lateral Sclerosis Functional Rating
      Scale (ALSFRS) scores. METHODS: ALSFRS scores and patient survival times were
      simulated based on estimates from a recent clinical trial. Six analysis
      approaches were applied to the data. Each approach was based on ALSFRS scores,
      the survival time, or a combination of the 2. The power of each approach to
      detect potential treatment effects was estimated. RESULTS: When the treatment
      acted solely on the change in ALSFRS, the shared parameter model provided the
      most power, although all of the models based on random effects were similar. As
      the effect on survival increased, rank-based analysis showed potential gains in
      power. Survival analysis was superior under a small effect on ALSFRS and a larger
      effect on mortality. CONCLUSIONS: The shared parameter model and rank-based
      approach can offer improvements in power over traditional approaches.

PMID- 22987691
TI  - Foot drop splints improve proximal as well as distal leg control during gait in
      Charcot-Marie-Tooth disease.
AB  - INTRODUCTION: During walking, people with Charcot-Marie-Tooth (CMT) disease may
      compensate for distal weakness by using proximal muscles. We investigated the
      effect of different AFOs on distal leg control and proximal compensatory actions.
      METHODS: Fourteen people with CMT were tested while wearing 3 types of ankle-foot
      orthosis (AFO) bilaterally compared with shoes alone. Walking was assessed using
      three-dimensional gait analysis. Stiffness of the splints was measured by
      applying controlled 5-degree ankle stretches using a motor. RESULTS: The results
      showed that each AFO significantly stiffened the ankle and increased ankle
      dorsiflexion at foot clearance compared with shoes alone. At push off, peak ankle
      power generation was reduced, but only with 1 type of AFO. A significant decrease
      in hip flexion amplitude during the swing phase was observed with all 3 AFOs.
      CONCLUSIONS: These results indicate that AFOs reduce foot drop and remove the
      need for some proximal compensatory action.

PMID- 22987692
TI  - The assisted 6-minute cycling test to assess endurance in children with a
      neuromuscular disorder.
AB  - INTRODUCTION: For late- or non-ambulant children with a neuromuscular disorder no
      suitable endurance tests are currently available. We developed the assisted 6
      minute cycling test (A6MCT) for the legs and arms and investigated its
      psychometric properties in healthy boys and boys with Duchenne muscular dystrophy
      (DMD). METHODS: Ninety-nine healthy boys and 30 boys with DMD (12 wheelchair
      dependent) performed the A6MCT. Seventy healthy boys also performed the 6-minute
      walk test (6MWT), and 23 boys performed the A6MCT twice within 2 weeks. Boys with
      DMD also performed the Motor Function Measure (MFM). RESULTS: The A6MCT was
      feasible for >90% of all boys. Boys with DMD achieved fewer cycling revolutions
      than controls. The A6MCT was positively correlated with the 6MWT and was
      reproducible in healthy boys, and it correlated with disease severity in boys
      with DMD. CONCLUSIONS: The A6MCT is a promising outcome measure for the follow-up
      of non-ambulant children with a neuromuscular disorder.

PMID- 22987694
TI  - Elimination of dysphagia using ultrasound guidance for botulinum toxin injections
      in cervical dystonia.
AB  - INTRODUCTION: Dysphagia is a common side effect after botulinum toxin injections
      for cervical dystonia, with an incidence of 10-40%, depending upon the study and
      dose used. METHODS: Our study consisted of 5 preselected women who met criteria
      for cervical dystonia and subsequent dysphagia after electromyography (EMG)
      guided injections. Injections were performed with ultrasound (US) imaging, and
      the effects on swallowing were examined. Separately, sternocleidomastoid (SCM)
      thickness in healthy controls and treated patients was measured. RESULTS: There
      were 34 episodes of dysphagia over 98 injection sessions using EMG guidance for a
      cumulative rate of 34.7%. Using US plus EMG guidance, there was 0% dysphagia
      across 27 injection sessions. SCM thickness was <1.1 cm. CONCLUSION: US combined
      with EMG guidance eliminated recurrent dysphagia after botulinum toxin treatment,
      possibly by keeping the injectate within the SCM.

PMID- 22987693
TI  - Manual needle placement: accuracy of botulinum toxin A injections.
AB  - INTRODUCTION: Electrophysiological or ultrasound guidance can facilitate
      botulinum toxin A (BoNt-A) injection accuracy, but clinical landmarks and
      palpation are often used for superficial muscles. We evaluated the accuracy of
      manual needle placement in the gastrocnemius muscles (GC) guided only by
      anatomical landmarks and palpation. METHODS: Bilateral limbs from 30 cadavers
      were used to evaluate ink injection into the GC. One anatomist and one orthopedic
      surgeon verified the accuracy of manual needle placement postinjection by calf
      muscle dissection. Injection was considered a failure if the ink was not located
      in the head of the target GC. RESULTS: One hundred twenty-one practitioners were
      evaluated. Fifty-two injections were successful (43%), and 69 failed (57%). This
      result was unrelated to injector experience (P = 0.097). CONCLUSIONS: Our
      findings show a poor success rate, regardless of injector experience. Therefore,
      muscle palpation and anatomical landmarks are insufficient to ensure the accuracy
      of BoNt-A injections, even for large, superficial muscles.

PMID- 22987695
TI  - A more detailed mechanism to explain the "bands of Fontana" in peripheral nerves.
AB  - INTRODUCTION: In 1779, Fontana identified transverse and oblique bands along
      peripheral nerves. Subsequent studies pointed alternatively to endoneural or
      perineural components as the cause. Our aim was to clarify these conflicting
      findings. METHODS: Recoiling of the bands of Fontana was video-recorded in the
      rat sciatic nerve. Computer-assisted design (CAD) software was used to model the
      nerve by interference figures. RESULTS: In vivo microdissection showed
      distinctive, black-and-white, closely packed bands in the perineurium, which
      differed from the widely spaced, translucent, dark/pale gray, staggered bands in
      the endoneurium. CAD merging of these 2 patterns produced images resembling the
      bands observed in vivo. CONCLUSIONS: Two repetitive structures with different
      characteristics, 1 in the perineurium and the other in the endoneurium, merge to
      give the appearance of these bands.

PMID- 22987696
TI  - Quadriceps and ankle dorsiflexor strength in chronic obstructive pulmonary
      disease.
AB  - INTRODUCTION: Quadriceps strength and size are commonly reduced in chronic
      obstructive pulmonary disease (COPD). We wished to assess volitional and
      nonvolitional ankle dorsiflexor strength in COPD. METHODS: Quadriceps and ankle
      dorsiflexor strength were measured by maximum voluntary contraction (MVC) and by
      twitch responses to supramaximal femoral and fibular nerve stimulation. Cross
      sectional areas of the tibialis anterior (TA(CSA)) and rectus femoris muscles
      (RF(CSA)) were measured by ultrasound. RESULTS: Eighteen elderly subjects and 20
      COPD patients [mean(SD) %predictedFEV(1) 50(20)%] participated. No significant
      difference in fat-free mass index, ankle dorsiflexor strength, or TA(CSA) were
      observed in the presence of reduced quadriceps strength and size in COPD [mean
      MVC difference: -10.9 kg (95% confidence interval {CI}: -17.1 kg to -4.8 kg, P <
      0.01; mean RF(CSA) difference -119 mm(2), 95% CI: -180 mm(2) to -58 mm(2), P <
      0.01)]. CONCLUSIONS: Ankle dorsiflexor strength is less attenuated than
      quadriceps strength in COPD patients with moderate airflow obstruction. Direct
      quadriceps assessment may be more relevant than measurement of lower limb fat
      free mass.

PMID- 22987697
TI  - Grip and knee extension muscle strength reflect a common construct among adults.
AB  - INTRODUCTION: Both grip and knee extension strength are often used to
      characterize overall limb muscle strength. We sought to determine if the measures
      actually reflect a common construct. METHODS: The isometric grip and knee
      extension strength of 164 healthy men and women (range, 18-85 years) were
      measured bilaterally using standard procedures. Pearson correlations (r),
      Cronbach alpha, principal components analysis, and multiple
      regression/correlation were used to investigate the dimensionality of the
      measures. RESULTS: Left and right grip forces and knee extension torques were
      highly correlated, internally consistent, and loaded on a single component.
      Gender and age explained the variance in both measures, but height added to the
      explanation of grip strength, whereas weight added to the explanation of knee
      extension strength. CONCLUSIONS: Among healthy adults, grip and knee extension
      strength reflect a common underlying construct. The measures, however, are
      affected differently by height and weight.

PMID- 22987698
TI  - Assessment of musculo-articular and muscle stiffness in young and older men.
AB  - INTRODUCTION: The aim of this cross-sectional study was to concurrently assess
      musculo-articular stiffness (MAS) and muscle stiffness (MS) of the knee extensors
      in younger and older individuals. METHODS: Fourteen young (22.1 +/- 3.0 years
      old) and 12 older (65.4 +/- 5.7 years old) men were tested for maximal voluntary
      contraction (MVC), rate of torque development (RTD), muscle thickness, MAS, and
      MS of knee extensors. RESULTS: MVC, RTD, and muscle thickness were higher in the
      younger group (288.6 vs. 194.3 Nm, 1319.5 vs. 787.0 Nm s(-1), 23.1 vs. 17.7 mm,
      respectively, P < 0.05). MAS normalized to the load supported (30% of MVC) was
      not different between groups (87.9 vs. 88.5 Nm(-1) kg(-1)), whereas the older
      group exhibited a higher level of normalized MS (23.2 vs. 18.6 Nm(-1) kg(-1), P <
      0.05). CONCLUSIONS: Determinants of MS have been highlighted along with their
      role in elevated MS. The unaltered level of MAS, which is functionally important
      in an aging population, might be achieved through a decrease in tendon stiffness.

PMID- 22987699
TI  - Reliability of neuromuscular measurements during explosive isometric
      contractions, with special reference to electromyography normalization
      techniques.
AB  - INTRODUCTION: This study determined the between-session reliability of
      neuromuscular measurements during explosive isometric contractions, with special
      consideration of electromyography (EMG) normalization. METHODS: Following
      familiarization, 13 men participated in 3 identical measurement sessions
      involving maximal and explosive voluntary contractions of the knee extensors,
      while force and surface EMG were recorded. Root mean square EMG amplitude was
      normalized to different reference measures: (evoked maximal M-wave peak-to-peak
      amplitude and area, maximum and sub-maximum voluntary contractions). RESULTS:
      Explosive voluntary force measurements were reliable on a group level, whereas
      within-subject reliability was low over the initial 50 ms and good from 100 ms
      onward. Normalization of EMG during explosive voluntary contractions,
      irrespective of the reference method, did not reduce the within-subject
      variability, but it did reduce substantially the variability between-subject.
      CONCLUSIONS: The high intra-individual variability of EMG and early phase
      explosive voluntary force production may limit their use to measuring group as
      opposed to individual responses to an intervention.

PMID- 22987700
TI  - Estimating electromyographic and heart rate fatigue thresholds from a single
      treadmill test.
AB  - INTRODUCTION: The purposes of this study were to (1) develop a fatigue threshold
      based on electromyography (EMG) and heart rate (HR) responses for treadmill
      running from a single incremental test; and (2) propose a new fatigue threshold
      called the RV(EMGFT) and RV(HRFT). METHODS: Eleven men performed incremental
      treadmill exercise to exhaustion on a single occasion. The RV(EMGFT) and RV(HRFT)
      were defined as the average of the highest velocity that resulted in a
      nonsignificant slope coefficient for the EMG amplitude versus time relationship
      and the lowest velocity that resulted in a significant positive slope
      coefficient. RESULTS: There was a significant (P < 0.05) difference between the 2
      thresholds [RV(EMGFT) = 11.7 +/- 0.6 km/h and RV(HRFT) = 8.3 +/- 0.8 km/h].
      CONCLUSIONS: The fatigue threshold for EMG amplitude and heart rate can be
      determined from a single incremental treadmill test, but there are differences
      between cardiac and neuromuscular factors of fatigue.

PMID- 22987701
TI  - Decay-accelerating factor 1 deficiency exacerbates Trypanosoma cruzi-induced
      murine chronic myositis.
AB  - INTRODUCTION: Murine infection with Trypanosoma cruzi (Tc) has been used to study
      the role of T-cells in the pathogenesis of human inflammatory idiopathic
      myositis. Absence of decay-accelerating factor 1 (Daf1) has been shown to enhance
      murine T-cell responses and autoimmunity. METHODS: To determine whether Daf1
      deficiency can exacerbate Tc-induced myositis, C57BL/6 DAF(+/+) and DAF(-/-) mice
      were inoculated with 5 * 10(4) trypomastigotes, and their morbidity, parasitemia,
      parasite burden, histopathology, and T-cell expansion were studied in the acute
      and chronic stages. RESULTS: DAF(-/-) mice had lower parasitemia and parasite
      burden but higher morbidity, muscle histopathology, and increased number of
      CD44(+) (activated/memory phenotype) splenic CD4(+) and CD8(+) T-cells.
      CONCLUSIONS: An enhanced CD8(+) T-cell immune-specific response may explain the
      lower parasitemia and parasite burden levels and the increase in
      histopathological lesions. We propose that Tc-inoculated DAF(-/-) mice are a
      useful model to study T-cell mediated immunity in skeletal muscle tissues.

PMID- 22987703
TI  - Discharge rates in electromyography distinguish early between peripheral and
      central paresis.
AB  - INTRODUCTION: Abnormally increased discharge rates (DRs) of motor unit potentials
      on concentric needle electromyography (CNEMG) indicate a loss of motor units in
      peripheral neurogenic lesions. METHODS: To determine when increased DRs occur
      during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG
      recordings of 19 patients with acute weakness of peripheral origin. RESULTS: The
      initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the
      lesion. Abnormally increased DRs (>=20/s) were found in all but 1 of the muscles
      in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all
      patients thereafter. The DRs depended on neither the kind of lesion nor the time
      between onset and CNEMG examination. CONCLUSIONS: The measurement of DRs of motor
      unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or
      worse to differentiate between a central and a peripheral lesion.

PMID- 22987702
TI  - Muscle function in a canine model of X-linked myotubular myopathy.
AB  - INTRODUCTION: We established a colony of dogs that harbor an X-linked MTM1
      missense mutation.Muscle from affected male dogs exhibits reduction and altered
      localization of the MTM1 gene product, myotubularin, and provides a model
      analogous to X-linked myotubular myopathy (XLMTM). METHODS: We studied hindlimb
      muscle function in age-matched canine XLMTM genotypes between ages 9 and 18
      weeks. RESULTS: By the end of the study, affected dogs produce only ~15% of the
      torque generated by normals or carriers (0.023 +/- 0.005 vs. 0.152 +/- 0.007 and
      0.154 +/- 0.003 N-m/kg body mass, respectively, P < 0.05) and are too weak to
      stand unassisted. At this age, XLMTM dogs also demonstrate an abnormally low
      twitch:tetanus ratio, a right-shifted torque-frequency relationship and an
      increase in torque during repetitive stimulation (P < 0.05). CONCLUSIONS: We
      hypothesize that muscle weakness results from impaired excitation-contraction (E
      C) coupling. Interventions that improve E-C coupling might be translated from the
      XLMTM dog model to patients.

PMID- 22987704
TI  - Cardiac screening investigations in adult-onset progressive external
      ophthalmoplegia patients.
AB  - INTRODUCTION: Patients with mitochondrial myopathies may develop cardiac
      complications such as cardiomyopathy and/or cardiac conduction defects. To
      identify these potentially life-threatening and treatable conditions, it is
      common practice to screen patients intermittently with electrocardiography and
      echocardiography. The optimal time interval for such screening investigations is
      unknown. We developed this study to review our screening results in adult-onset
      patients with progressive external ophthalmoplegia (PEO). METHODS: This study was
      a retrospective review of PEO patients with 5 years or more of cardiac screening
      investigations who did not have any cardiac symptoms. RESULTS: Fifteen patients
      were included, and cardiomyopathy was identified on screening echocardiogram in 1
      patient. Four patients had other abnormalities identified, which were unrelated
      to their mitochondrial myopathy. CONCLUSIONS: Only 1 patient in 15 developed
      cardiac complications related to mitochondrial disease during 5 years of follow
      up. We suggest that a screening interval of 3-5 years is probably appropriate for
      adult-onset PEO patients who do not have cardiac symptoms.

PMID- 22987705
TI  - Dorsal sural neuropathy: electrophysiological, ultrasonographic, and magnetic
      resonance imaging findings.
AB  - Dorsal sural neuropathy occurs infrequently as a result of compression of the
      nerve due to various etiologies.We describe a 52-year-old diabetic woman with
      dorsal sural neuropathy. The diagnosis was based on clinical,
      electrophysiological, ultrasonographic, and magnetic resonance imaging (MRI)
      findings. This case report demonstrates the usefulness of electrophysiological
      and imaging studies, including ultrasonography, in the diagnosis of dorsal sural
      neuropathy.

PMID- 22987706
TI  - Limb-girdle myasthenia with tubular aggregates associated with novel GFPT1
      mutations.
AB  - INTRODUCTION: Limb-girdle myasthenia with tubular aggregates (LGM with TAs) is a
      subtype of congenital myasthenic syndrome caused by recessive mutations of
      glutamine-fructose-6-phosphate transaminase 1 (GFPT1). METHODS: Clinical and
      neurophysiological assessment was made in a Korean boy who had proximal limb
      muscle weakness. Findings suggested a diagnosis of congenital myasthenic
      syndrome. RESULTS: Muscle biopsy disclosed numerous TAs in muscle fibers, and DNA
      sequence analysis disclosed 2 novel missense mutations (p.E256Q and p.M499T) in
      GFPT1. Treatment with oral cholinesterase inhibitors produced a dramatic
      improvement in muscle strength. CONCLUSIONS: GFPT1 is the key enzyme in the
      hexosamine biosynthesis pathway, and mutations in GFPT1 cause defective
      glycosylation in the proteins of the neuromuscular junction. Identification of
      LGM with TAs among patients with congenital myasthenic syndrome is important
      because treatment with cholinesterase inhibitors can produce symptomatic
      improvement.

PMID- 22987707
TI  - Spinal Charcot-Marie-Tooth disease: a reappraisal.
AB  - INTRODUCTION: Distal hereditary motor neuropathy (dHMN) is characterized by
      isolated distal muscle atrophy without sensory deficit. Nevertheless, clinical
      sensory loss has been reported despite preserved sensory nerve conduction in a
      few patients, thus differentiating these cases from the classical type 2 Charcot
      Marie-Tooth disease (CMT2). METHODS: We report 4 patients who presented with
      clinical sensory and motor neuropathy and normal peripheral sensory nerve
      conduction studies and were investigated with complete electrophysiological
      studies, including somatosensory evoked potentials (SEP). RESULTS: These patients
      had a clinical presentation of classical CMT with isolated axonal motor
      neuropathy suggestive of dHMN. Interestingly, tibial nerve SEPs showed
      abnormalities suggestive of proximal involvement of dorsal roots that may explain
      the clinical somatosensory disturbances. CONCLUSIONS: These cases support the
      concept of spinal CMT that should be recognized as an intermediate form between
      dHMN and CMT2. SEP recording was helpful in defining a more precise phenotype of
      spinal CMT.

PMID- 22987708
TI  - Neuropathy in chronic graft-versus-host disease caused by donor T cells.

PMID- 22987709
TI  - Pathophysiological basis of contralateral reinnervation in facial palsy.

PMID- 22987710
TI  - Stiff person syndrome and rituximab.

PMID- 22987718
TI  - Development, optimisation and validation of a stability-indicating HPLC method of
      achyrobichalcone quantification using experimental designs.
AB  - INTRODUCTION: Achyrobichalcone is a new biflavonoid found in Achyrocline
      satureioides. It is structurally similar to other bioactive bichalcones that were
      proven to exert anti-cancer activity. Recently we isolated several
      achyrobichalcone batches on a semi-preparative scale, showing the need to assess
      the quality and stability of this substance by analytical methods. OBJECTIVE: To
      develop and validate a stability-indicating HPLC method of achyrobichalcone
      quantification using experimental designs. METHOD: The method was developed and
      optimised by Box-Behnken design using column temperature, flow rate and
      acetonitrile content in the mobile phase as factors and system suitability
      parameters as responses. Validation parameters were determined according to
      official compendiums. Robustness was determined by Plackett-Burman design.
      Stability of achyrobichalcone was assessed in alkaline, acid, oxidative, thermal
      and photolytic stress conditions. RESULTS: The ideal chromatographic conditions
      were defined from the optimisation: 37 % of acetonitrile, flow rate of 1.2 mL/min
      and 33 degrees C temperature. All factors were significant for the resolution
      between achyrobichalcone and impurities peaks and for the retention factor. The
      mathematical model developed exhibited a good predictive capacity, and the design
      proved suitable. The HPLC method was successfully validated, being linear,
      specific, accurate and precise. The robustness test revealed that the flow rate
      and detection wavelength should be strictly controlled, as they affect
      achyrobichalcone concentration. The analyte was unstable only in alkaline media.
      CONCLUSION: The new method developed affords evaluation of the quality of
      achyrobichalcone obtained by isolation, and indicates the stability of the
      molecule under various stress conditions.

PMID- 22987719
TI  - Serum levels of fibroblast growth factor 2 in children with orthopedic diseases:
      potential role in predicting bone healing.
AB  - Fibroblast growth factor 2 (FGF-2) plays an important role in the early phases of
      bone healing. In this study, we measured FGF-2 serum levels in 88 children
      undergoing surgical treatment for congenital (n = 49) or acquired (n = 39)
      orthopedic conditions, which were associated (n = 35) or not (n = 53) with bone
      lesions, to assess whether serum levels of FGF-2 varied according to the
      underlying disease and may predict clinical outcomes. FGF-2 serum levels were
      significantly lower in patients who did not heal after surgery (p = 0.008).
      Diagnostic accuracy was validated statistically, and the ROC curve provided a
      threshold value useful in discriminating good versus poor outcomes. The
      relationship between FGF-2 and bone healing was supported by in vitro
      experiments. A mineralization assay was performed on bone marrow stromal cells
      from three patients with congenital pseudarthrosis, who had low serum levels of
      FGF-2 and a poor clinical outcome after surgical treatment. Autologous serum
      alone was not sufficient to induce in vitro mineralization, but it did occur when
      cells were cultured with different sources of exogenous growth factors (GFs),
      including recombinant FGF-2 and homologous serum collected from children with
      fractures, high FGF-2 levels, and a good clinical outcome. In conclusion, our
      findings suggest that osteoinductive GFs are essential for bone repair, and that
      the amount of circulating FGF-2 may predict bone healing.

PMID- 22987721
TI  - A tape recorder as a therapeutic "witness" in the treatment of an 8-year-old
      girl.
AB  - A tape-recorded session of an early moment in an 8-year-old girl's psychotherapy
      experience is presented. The use of the recording device is immediately taken up
      by the child as a means of creating a "witness" for her depiction of both
      intensely distorted experiences of her therapist and poignant portrayals of her
      life as miserable and despairing. A discussion of both the process and the
      content generated from the use of the tape recorder is described, with
      implications drawn as to its effectiveness in the therapeutic process.

PMID- 22987720
TI  - CNP/NPR2 signaling maintains oocyte meiotic arrest in early antral follicles and
      is suppressed by EGFR-mediated signaling in preovulatory follicles.
AB  - Oocyte meiosis is arrested at prophase I by factors secreted from surrounding
      somatic cells after oocytes acquire meiotic competence at an early antral stage,
      and meiosis resumes in preovulatory follicles as a result of the luteinizing
      hormone (LH) surge. Recently, signaling by C-type natriuretic peptide (CNP)
      through its receptor, natriuretic peptide receptor 2 (NPR2), was found to be
      essential for meiotic arrest at the late antral stage. Whether or not CNP/NPR2
      signaling maintains oocyte meiotic arrest in earlier follicular stages and how it
      is associated with meiotic resumption induced by the LH surge is unclear. In this
      study, we examined the expression of Nppc and Npr2, respectively encoding CNP and
      NPR2, in the ovaries of immature mice. Nppc and Npr2 mRNA were specifically
      expressed in the outer and inner granulosa cell layers, respectively, in early
      antral follicles. Histological analysis of mice with a mutation in Npr2 revealed
      precocious resumption of oocyte meiosis in early antral follicles. Ovaries of
      mice treated with excess human chorionic gonadotropin (hCG) exhibited markedly
      decreased Nppc mRNA levels in granulosa cells of preovulatory follicles.
      Moreover, we found that amphiregulin, a mediator of LH/hCG activity through
      epidermal growth factor receptor (EGFR), suppressed Nppc mRNA levels in cultured
      granulosa cells. These results suggest that CNP/NPR2 signaling is essential for
      oocyte meiotic arrest in early antral follicles and that activated
      LH/amphiregulin/EGFR signaling pathway suppresses this signal by downregulating
      Nppc expression.

PMID- 22987722
TI  - Mapping and correction of the CMM workspace error with the use of an electronic
      gyroscope and neural networks--practical application.
AB  - The article presents the application of neural networks in determining and
      correction of the deformation of a coordinate measuring machine (CMM) workspace.
      The information about the CMM errors is acquired using an ADXRS401 electronic
      gyroscope. A test device (PS-20 module) was built and integrated with a
      commercial measurement system based on the SP25M passive scanning probe and with
      a PH10M module (Renishaw). The proposed solution was tested on a Kemco 600 CMM
      and on a DEA Global Clima CMM. In the former case, correction of the CMM errors
      was performed using the source code of WinIOS software owned by The Institute of
      Advanced Manufacturing Technology, Cracow, Poland and in the latter on an
      external PC. Optimum parameters of full and simplified mapping of a given layer
      of the CMM workspace were determined for practical applications. The proposed
      method can be employed for the interim check (ISO 10360-2 procedure) or to detect
      local CMM deformations, occurring when the CMM works at high scanning speeds (>20
      mm/s).

PMID- 22987723
TI  - Specific frequency bands of amplitude low-frequency oscillation encodes
      personality.
AB  - The biological model of extraversion and neuroticism identified by Eysenck has
      stimulated increasing interest in uncovering neurobiological substrate of the two
      fundamental dimensions. Here we aim to explore brain disturbances underlying
      extraversion and neuroticism in 87 healthy individuals using fractional amplitude
      of low-frequency fluctuations (LFF) on resting-state functional magnetic
      resonance imaging. Two different frequency bands, Slow-5 (0.01-0.027 Hz)
      exhibiting higher power and involving larger brain regions, and Slow-4 (0.027
      0.073 Hz) exhibiting less power and emerging locally, were analyzed. Our results
      showed a positive correlation between LFF amplitude at Slow-5 and extraversion in
      medial prefrontal cortex and precuneus, important portions of the default mode
      network, thus suggesting a link between default network activity and personality
      traits. LFF amplitude at Slow-5 was correlated positively with neuroticism in
      right posterior portion of the frontal lobe, further validating neuroticism with
      frontal lateralization. In addition, LFF amplitude at Slow-4 was negatively
      associated with extraversion and neuroticism in left hippocampus (HIP) and
      bilateral superior temporal cortex (STC) respectively, supporting the
      hypothesized (inverse) relationship between extraversion and resting arousal,
      also implying neural circuit underlying emotional process influencing on
      personality. Overall, these findings suggest the important relationships, between
      personality and LFF amplitude dynamic, depend on specific frequency bands.

PMID- 22987725
TI  - Fabrication of ssDNA/oligo(ethylene glycol) monolayers and complex nanostructures
      by an irradiation-promoted exchange reaction.

PMID- 22987724
TI  - Towards a new tuberculosis drug: pyridomycin - nature's isoniazid.
AB  - Tuberculosis, a global threat to public health, is becoming untreatable due to
      widespread drug resistance to frontline drugs such as the InhA-inhibitor
      isoniazid. Historically, by inhibiting highly vulnerable targets, natural
      products have been an important source of antibiotics including potent anti
      tuberculosis agents. Here, we describe pyridomycin, a compound produced by
      Dactylosporangium fulvum with specific cidal activity against mycobacteria. By
      selecting pyridomycin-resistant mutants of Mycobacterium tuberculosis, whole
      genome sequencing and genetic validation, we identified the NADH-dependent enoyl-
      (Acyl-Carrier-Protein) reductase InhA as the principal target and demonstrate
      that pyridomycin inhibits mycolic acid synthesis in M. tuberculosis. Furthermore,
      biochemical and structural studies show that pyridomycin inhibits InhA directly
      as a competitive inhibitor of the NADH-binding site, thereby identifying a new,
      druggable pocket in InhA. Importantly, the most frequently encountered isoniazid
      resistant clinical isolates remain fully susceptible to pyridomycin, thus opening
      new avenues for drug development. ->See accompanying article
      http://dx.doi.org/10.1002/emmm.201201811.

PMID- 22987726
TI  - Involvement of NOS3 in RA-Induced neural differentiation of human NT2/D1 cells.
AB  - Nitric oxide (NO) plays a key role in neurogenesis as a regulator of cell
      proliferation and differentiation. NO is synthesized from the amino acid L
      arginine by nitric oxide synthases (NOS1, NOS2, and NOS3), which are encoded by
      separate genes and display different tissue distributions. We used an in vitro
      model of RA-induced neural differentiation of NT2 cells to examine which of the
      three NO-synthesizing enzymes is involved in this process. The results revealed a
      transient induction of NOS3 (known as the constitutively expressed endothelial
      nitric oxide synthase; eNOS) during the time course of the RA treatment. The peak
      of gene expression and the nuclear presence of NOS3 protein coincided with cell
      cycle exit of NT2-derived neuronal precursors. The subsequent analysis of
      cytosine methylation and histone H3 acetylation of the human NOS3 5' regulatory
      sequences indicated that epigenetic modifications, especially upstream of the
      proximal promoter (-734 to -989, relative to exon 2 TSS at +1), were also taking
      place. NOS1 was expressed only in the differentiated neurons (NT2-N), whereas
      NOS2 was not expressed at all in this cellular model. Thus, a burst of NO
      production, possibly required to inhibit neural cell proliferation, was generated
      by the transient expression of NOS3. This pattern of gene expression, in turn,
      required epigenetic remodeling of its regulatory region.

PMID- 22987728
TI  - [Hungarian psychopharmacology -- what direction?].

PMID- 22987729
TI  - The message of the survival curves: I. Composite analysis of long-term treatment
      studies in bipolar disorder.
AB  - RATIONALE: There is a shortage of studies analyzing the time course of recurrent
      episodes and comparing effectiveness of long-term treatments in bipolar disorder.
      'Number needed to treat' (NNT) analyses have been proven to be useful for
      clinically meaningful comparisons, but results vary considerably among studies.
      The survival curves of different trials also show a great variability preventing
      reliable conclusions on the time course of maintenance therapies. The variance of
      survival analyses on long-term medication management can be reduced with
      increasing the statistical power by combining the life-tables of individual
      studies. METHODS: In this study the survival tables of 28 studies on maintenance
      treatment of bipolar disorder were reconstructed from the published diagrams, and
      the numbers of relapsed patients in the original studies were estimated for
      plotting composite survival curves of an inactive, mono- and combination therapy
      arm. The review was finally based on 5231 subjects. RESULTS: The resulting
      composite diagrams indicate that within the first year 48% of patients on
      monotherapy, and 35% on combination therapy experienced recurrence of any
      affective episode ('early relapsers'). The rest of the patient population was
      affected by recurrences in a smaller rate over a more extended period of time
      ('late relapsers'). For a favorable outcome at 40 months of episode prevention in
      bipolar disorder the NNT was 6 for mono- and 3 for combination therapy. Log-rank
      analyses of the composite data supported the effectiveness of both medication
      protocols over placebo, and the superiority of drug combination over monotherapy;
      though there were some indications of decreased efficacy in the two treatment
      arms after extended maintenance. CONCLUSIONS: Composite analysis offers increased
      statistical power for studying the time course of survival data. Mood episodes in
      bipolar disorder are likely to recur early on and relapses in "real-life" can be
      more frequent than the rates published here. Our results favor combination
      therapy for the long-term management of bipolar disorder. Concerns are expressed
      that NNT analyses have significant limitations when applied to recurring events
      with cumulative deterioration instead of cases where cumulative improvement is
      expected over time.

PMID- 22987727
TI  - Potential strategies and biosafety protocols used for dual-use research on highly
      pathogenic influenza viruses.
AB  - Influenza A viruses (IAVs), particularly the highly pathogenic avian influenza
      H5N1, have posed a substantial threat to public health worldwide. Although the
      laboratory generation of the mutant influenza virus H5N1 with airborne
      transmissibility among mammals, which has been considered as a dual-use research,
      may benefit the development of effective vaccines and therapeutics against the
      emerging infectious agents, it may also pose threats to national biosecurity,
      laboratory biosafety, and/or public health. This review introduces the
      classification and characterization of IAVs, pinpoints historic pandemics and
      epidemics caused by IAVs, emphasizes the significance and necessity of biosafety,
      summarizes currently established biosafety-related protocols for IAV research,
      and provides potential strategies to improve biosafety protocols for dual-use
      research on the highly pathogenic avian influenza viruses and other emerging
      infectious agents.

PMID- 22987730
TI  - Marking the markers of Alzheimer's: too good to diagnose, too bad to use?
AB  - One of the most important neurodegenerative diseases of our time is Alzheimer's
      disease, which mainly affects the elderly population. The accumulation of beta
      amyloid and tau protein in the brain tissue is the most characteristic
      pathomechanical event of the disease, later causing neuronal cell death. Setting
      up an accurate diagnosis of Alzheimer's disease has essentially changed recently,
      since besides psychometry, neurochemical and neuroimaging examinations are also
      gaining greater importance in the clinical routine. Thanks to the widening of
      diagnostic methods, in the future the disease could be recognised even during the
      preclinical phase. The most remarkable source of brain-derived compounds is the
      cerebrospinal fluid. Although obtaining cerebrospinal fluid is greatly
      unpleasant, it poses a low risk and is frequently used as part of the diagnostic
      procedure. The assay of cerebrospinal fluid means the identification of the level
      of beta-amyloid(1-42), tau and phospho-tau and their ratio, but to get more
      specific and sensitive investigations there is intensive research work both on
      the utility of their combination and on finding even more specific biomarkers.
      This review gives a summary of the biomarkers that are being used and being
      researched for the diagnostic tests of both familial and sporadic forms of
      Alzheimer's disease. Other notable sources of neurochemical compounds are the
      serum and the plasma, however, the identification of their biomarkers is under
      preclinical examinations. Unfortunately neither the validation of these markers
      nor the consistent acceptance of the experimental results is possible due to the
      wide range of protocols in international research. The importance of biomarkers
      in the development of potential drug candidates is also discussed.

PMID- 22987731
TI  - Associations between season of birth and suicide: a brief review.
AB  - Suicide is a complex behaviour contributing to a significant number of
      unnecessary deaths worldwide. Accordingly, the quest for suicide risk factors is
      one of the most intensively developing issues of psychiatric research. In the
      last few decades a number of interesting results have been published about
      associations between season of birth (SOB) and several physiological and
      pathological aspects of human life, while, in regard to neuroscience, several
      investigations confirmed that SOB is associated with the risk of several major
      neuropsychiatric disorders and suicide as well. Research concerning the possible
      causative factors behind these associations were also performed suggesting that
      SOB-associated factors (including day length; seasonal changes in maternal
      nutritional status and vitamin D levels; seasonal alterations in incidence of
      some common infective disorders) contribute to neurochemical and consequentially
      temperament/personality trait alterations which may mediate the associations
      between SOB and psychiatric disorders. Other results indicate an uneven
      distribution of monoamine metabolism-related genotypes in different birth season
      cohorts possibly underpinning the effects of SOB. In our narrative review we
      summarize and discuss the available literature on the relevance of the most
      important findings concerning the above fields.

PMID- 22987732
TI  - [Antipsychotic drug combinations in the treatment of schizophrenia. A review of
      the literature].
AB  - Main indication for antipsychotic medication is the treatment of schizophrenia
      and other psychotic disorders. Influential protocols in the treatment of
      schizophrenia recommend the use of antipsychotics in monotherapy. In case of
      therapy resistance, combination of antipsychotics is a feasible option. Applying
      antipsychotics in combination is common in clinical practice, although existing
      efficacy and safety data concerning antipsychotic combinations are scarce.
      Authors, after reviewing existing scientific data, make attempt to give
      recommendations for combined antipsychotic therapy in everyday clinical practice.

PMID- 22987733
TI  - [Maintenance therapy in schizophrenia -- a brief review of the literature].
AB  - This article reviews the role of the first and second generation antipsychotics
      in the long-term treatment of schizophrenia. The different forms of course, the
      relationship between maintenance treatment and relapse rates, the influence of
      depot antipsychotics and adherence on the outcome, and other predictive factors
      will be addressed in the paper. The necessity of a survival meta-analysis is
      emphasized for the calculation of the 'number needed to treat', and for a
      detailed analysis of the time course of recurrences.

PMID- 22987734
TI  - Additional case of an uncommon 22q11.2 reciprocal rearrangement in a
      phenotypically normal mother of children with 22q11.2 deletion and 22q11.2
      duplication syndromes.

PMID- 22987735
TI  - Selective capture of anti-A antibodies from human blood using a novel integrated
      bead and hollow fiber module.
AB  - Anti-A/B antibody removal from blood in the peritransplantation period
      facilitates ABO-incompatible transplantation and significantly increases the
      donor pool. We have been developing an anti-A/B immunoadsorption device (BSAF),
      compatible with whole blood perfusion. The BSAF is based on integrated
      microfiltration hollow fibers with antibody capturing beads uniformly distributed
      within the fiber interstitial space. In this study we fabricated BSAF prototypes,
      appropriately scaled down from a conceptual clinical scale device. We then, for
      the first time, measured the time course of anti-A capture from blood samples
      recirculating through the scaled down BSAF devices. We observed a significant
      reduction in IgM (96% +/- 5%, n = 5, p < 0.001), and IgG (81% +/- 18%, n = 5, p <
      0.05) anti-A antibody titers within 2 h. We did not observe a significant change
      between the initial and final values of hematocrit, total plasma protein
      concentration, plasma free hemoglobin concentration, and anti-B antibody titer
      over five experiments. In conclusion we showed that the BSAF modules selectively
      removed anti-A antibodies from blood in a simple one step process, without
      requiring a separate plasmapheresis unit.

PMID- 22987737
TI  - Graphene nanosheets as a platform for the 2D ordering of metal oxide
      nanoparticles: mesoporous 2D aggregate of anatase TiO2 nanoparticles with
      improved electrode performance.
AB  - Graphene nanosheets are successfully applied as an effective platform for the 2D
      ordering of metal oxide nanoparticles. Mesoporous 2D aggregates of anatase TiO(2)
      nanoparticles are synthesized by the heat treatment of the uniformly hybridized
      nanocomposite of layered titanate-reduced graphene oxide (RGO) at elevated
      temperatures. The precursor layered titanate-RGO nanocomposite is prepared by
      self-assembly of anionic RGO nanosheets and cationic TiO(2) nanosols. The
      calcination of the as-prepared layered titanate-RGO nanocomposite at 500  degrees
      C induces a structural and morphological change of layered titanate nanoplates
      into anatase TiO(2) nanoparticles without significant modification of the RGO
      nanosheet. Increasing the heating temperature to 600  degrees C gives rise to
      elimination of the RGO component, leading to the formation of sheetlike porous
      aggregates of RGO-free TiO(2) nanoparticles. The nanocomposites calcined at 500
      700  degrees C display promising functionality as negative electrodes for lithium
      ion batteries. Among the present calcined derivatives, the 2D sheet-shaped
      aggregate of TiO(2) nanoparticles obtained from calcination at 600  degrees C
      delivers the greatest specific discharge capacity with good capacity retention
      for all current density conditions applied. Such superior electrode performance
      of the nanocomposite calcined at 600  degrees C is attributable both to the
      improved stability of the crystal structure and crystal morphology of titania and
      to the enhancement of Li(+) ion transport through the enlargement of mesopores.
      The present findings clearly demonstrate the usefulness of RGO nanosheets as a
      platform for 2D-ordered superstructures of metal oxide nanoparticles with
      improved electrode performance.

PMID- 22987736
TI  - Prediction of protein domain boundaries from inverse covariances.
AB  - It has been known even since relatively few structures had been solved that
      longer protein chains often contain multiple domains, which may fold separately
      and play the role of reusable functional modules found in many contexts. In many
      structural biology tasks, in particular structure prediction, it is of great use
      to be able to identify domains within the structure and analyze these regions
      separately. However, when using sequence data alone this task has proven
      exceptionally difficult, with relatively little improvement over the naive method
      of choosing boundaries based on size distributions of observed domains. The
      recent significant improvement in contact prediction provides a new source of
      information for domain prediction. We test several methods for using this
      information including a kernel smoothing-based approach and methods based on
      building alpha-carbon models and compare performance with a length-based
      predictor, a homology search method and four published sequence-based predictors:
      DOMCUT, DomPRO, DLP-SVM, and SCOOBY-DOmain. We show that the kernel-smoothing
      method is significantly better than the other ab initio predictors when both
      single-domain and multidomain targets are considered and is not significantly
      different to the homology-based method. Considering only multidomain targets the
      kernel-smoothing method outperforms all of the published methods except DLP-SVM.
      The kernel smoothing method therefore represents a potentially useful improvement
      to ab initio domain prediction.

PMID- 22987738
TI  - Selective and sensitive fluorescent turn-off chemosensors for Fe3+.
AB  - Two novel chemosensors (2a and 2b) were synthesized by facile condensation of the
      binding unit (L-histidine) and the fluorophores (anthracene and dansyl groups).
      Both of them displayed high selectivity and sensitivity towards Fe(3+) over other
      metal ions in aqueous solution. The sensing mechanism was based on the
      paramagnetic property of Fe(3+) that would lead to fluorescence quenching of the
      fluorophores when Fe(3+) was bound to the recognition units. The results showed
      that l-histidine was a good coordination motif for Fe(3+) and both the anthracene
      and dansyl groups can sensitively report the sensing information.

PMID- 22987739
TI  - HPLC-ESI-QTOF-MS as a powerful analytical tool for characterising phenolic
      compounds in olive-leaf extracts.
AB  - INTRODUCTION: Olea europaea L. leaves may be considered a cheap, easily available
      natural source of phenolic compounds. In a previous study we evaluated the
      possibility of obtaining bioactive phenolic compounds from olive leaves by
      pressurised liquid extraction (PLE) for their use as natural anti-oxidants. The
      alimentary use of these kinds of extract makes comprehensive knowledge of their
      composition essential. OBJECTIVE: To undertake a comprehensive characterisation
      of two olive-leaf extracts obtained by PLE using high-performance liquid
      chromatography coupled to electrospray ionisation and quadrupole time-of-flight
      mass spectrometry (HPLC-ESI-QTOF-MS). METHOD: Olive leaves were extracted by PLE
      using ethanol and water as extraction solvents at 150 degrees C and 200 degrees C
      respectively. Separation was carried out in a HPLC system equipped with a C18
      column working in a gradient elution programme coupled to ESI-QTOF-MS operating
      in negative ion mode. RESULTS: This analytical platform was able to detect 48
      compounds and tentatively identify 31 different phenolic compounds in these
      extracts, including secoiridoids, simple phenols, flavonoids, cinnamic-acid
      derivatives and benzoic acids. Lucidumoside C was also identified for the first
      time in olive leaves. CONCLUSION: The coupling of HPLC-ESI-QTOF-MS led to the in
      depth characterisation of the olive-leaf extracts on the basis of mass accuracy,
      true isotopic pattern and tandem mass spectrometry (MS/MS) spectra. We may
      conclude therefore that this analytical tool is very valuable in the study of
      phenolic compounds in plant matrices.

PMID- 22987740
TI  - The mechanical environment in Dupuytren's contracture determines cell
      contractility and associated MMP-mediated matrix remodeling.
AB  - Matrix metalloproteinases (MMPs) are expressed in Dupuytren's contracture and
      play a role in matrix remodeling. We tested the role of tension on contractility
      and MMP expression in Dupuytren's nodule and cord cells. Cells were subjected to
      pre-determined loading patterns of known repeatable magnitudes (static load,
      unloading, and overloading) and tested for MMP gene expression (MMP-1, -2, -9, 
      13, and TIMP-1, -2) and force generation using a tension-culture force monitor.
      Matrix remodeling was assessed by addition of cytochalasin D and residual matrix
      tension was quantified. Nodule compared to cord and control cells demonstrate
      greater force generation and remodeling (p < 0.05). Nodule cells subjected to a
      reduced load and overloading led to threefold increase of MMP-1, -2, and -9
      compared to static load, whilst cord and control cells only showed a twofold
      increase of MMP-9. Nodule cells subjected to overloading showed a twofold
      increase in TIMP-2 expression, whilst cord and control cells showed a twofold
      increase in TIMP-1 expression. Nodule cells differ from cord cells by increased
      force generation in response to changes in the mechanical environment and related
      MMP/TIMP-mediated matrix remodeling. In turn this may lead to permanent matrix
      shortening and digital contracture. Interventional therapies should be aimed at
      nodule cells to prevent contraction and subsequent permanent matrix remodeling.

PMID- 22987741
TI  - Craniofacial evolution in Polynesia: a geometric morphometric study of population
      diversity.
AB  - OBJECTIVES: This study tests differences in craniofacial size and shape
      attributed to demographic history and plastic responses to differing environments
      in the islands of Polynesia. The dispersal of modern humans into Polynesia
      provides a useful scenario to investigate the impact of migration on human
      craniofacial diversity. METHODS: Three dimensional geometric morphometric
      techniques are used to examine morphological diversity within Oceanic population
      samples. The importance of geographic and climatic variables is quantified by
      partial linear regression. RESULTS: The results show a homogeneous Polynesian
      morphology grouping in relation to neighboring regions. There is, however,
      considerable diversity within the Polynesian samples themselves. Natural
      selection due to environmental differences is not an important factor in the
      patterns of craniofacial diversity found in the samples. CONCLUSIONS: Historical
      patterns such as migration and population isolation influence patterns of
      craniofacial morphology within Polynesia, and our results demonstrate that
      morphological diversity can evolve in populations isolated for a relatively short
      period of time.

PMID- 22987742
TI  - Brain disorders where resources are scarce: The unfinished agenda.

PMID- 22987743
TI  - Membrane trafficking and transport: overview and neurologic implications.

PMID- 22987744
TI  - Peri-ictal restricted diffusion in heterotopic gray matter assessed by MRI.

PMID- 22987745
TI  - Evidence-based guideline update: NSAIDs and other complementary treatments for
      episodic migraine prevention in adults: report of the quality standards
      subcommittee of the American Academy of Neurology and the American Headache
      Society.

PMID- 22987746
TI  - Epilepsy surgery trends in the United States, 1990-2008.

PMID- 22987747
TI  - Teaching NeuroImages: Duret hemorrhage due to bilateral subdural hematomas
      causing internuclear ophthalmoplegia.

PMID- 22987748
TI  - Teaching NeuroImages: Neuropathic elbow arthropathy due to syringomyelia.

PMID- 22987749
TI  - Right Brain: past medical story.

PMID- 22987750
TI  - Fgf10 expression patterns in the developing chick inner ear.
AB  - The inner ear is a complex three-dimensional sensorial structure with auditory
      and vestibular functions. It originates from the otic placode, which invaginates,
      forming the otic vesicle; the latter gives rise to neurosensory and nonsensory
      elements of the adult membranous labyrinth. A hypothesis based on descriptive and
      experimental evidence suggests that the acquisition of discrete sensory patches
      during evolution of this primordium may be related to subdivision of an early
      pansensory domain. In order to gain insight into this developmental mechanism, we
      carried out a detailed analysis of the spatial and temporal expression pattern of
      the gene Fgf10, by comparing different markers of otic patterning and hair cell
      differentiation. Fgf10 expression labels a sensory-competent domain included in a
      Serrate-positive territory from which most of the sensory epithelia arise. Our
      data show that Fgf10 transcripts are present initially in a narrow ventromedial
      band of the rudimentary otocyst, extending between its rostral and caudal poles.
      During development, this Fgf10-expressing area splits repetitively into several
      separate subareas, creating six of the eight sensory organs present in birds.
      Only the lateral crista and the macula neglecta were initially Fgf10 negative,
      although they activated Fgf10 expression after their specification as sensory
      elements. These results allowed us to determine a timetable of sensory
      specification in the developing chick inner ear. The comparison of the expression
      pattern of Fgf10 with those of other markers of sensory differentiation
      contributes to our understanding of the mechanism by which vertebrate inner ear
      prosensory domains have arisen during evolution.

PMID- 22987751
TI  - Task and task-free FMRI reproducibility comparison for motor network
      identification.
AB  - Test-retest reliability of individual functional magnetic resonance imaging
      (fMRI) results is of importance in clinical practice and longitudinal
      experiments. While several studies have investigated reliability of task-induced
      motor network activation, less is known about the reliability of the task-free
      motor network. Here, we investigate the reproducibility of task-free fMRI, and
      compare it to motor task activity. Sixteen healthy subjects participated in this
      study with a test-retest interval of seven weeks. The task-free motor network was
      assessed with a univariate, seed-voxel-based correlation analysis.
      Reproducibility was tested by means of intraclass correlation (ICC) values and
      ratio of overlap. Higher ICC values and a better overlap were found for task fMRI
      as compared to task-free fMRI. Furthermore, ratio of overlap improved for task
      fMRI at higher thresholds, while it decreased for task-free fMRI, suggesting a
      less focal spatial pattern of the motor network during resting state. However,
      for both techniques the most active voxels were located in the primary motor
      cortex. This indicates that, just like task fMRI, task-free fMRI can properly
      identify critical brain areas for motor task performance. Although both fMRI
      techniques are able to detect the motor network, resting-state fMRI is less
      reliable than task fMRI.

PMID- 22987752
TI  - Variationally determined electronic states for the theoretical analysis of
      intramolecular interaction. II. Qualitative nature of the P-O bond in phosphine
      oxides.
AB  - We have developed a space-restricted wave function (SRW) method for the analysis
      of various types of intramolecular interactions. In this study, we demonstrate
      the applicability of our SRW method to the analysis of the nature of the P-O bond
      in phosphine oxide (R(3)PO), one of the hypervalent molecules. An interesting
      character of this bond has been extensively studied by focusing on the negative
      hyperconjugation of the O lone pair (n(O)) with the R(3)P group. We
      reinvestigated the nature of the bond in terms of a change in total energy to
      produce evidence for the validity of our method. The electronic states without
      the interaction involving three n(O) orbitals (R(3)P(+)-O(-)) produced by the
      method were used as reference states in the assessment of the effects of this
      n(O)-R(3)P interaction. The result confirms that this interaction plays an
      essential role in the nature of the bond and occurs between the n(O) orbitals and
      the P-R antibonding orbitals, in agreement with previous studies. A molecular
      orbital (MO)-pair analysis technique shows that the n(O)-R(3) P interaction is
      decomposed into the negative hyperconjugation and the Pauli repulsion.
      Considering a reference state where the P-O bond is completely broken (R(3)P(2+)
      . . .O(2-)) at an interacting distance, P-O bond formation is attributed to one
      sigma bond plus two 0.5 pi bonds. This is equivalent to three banana bonds highly
      polarized to the O atom. Consequently, the SRW method suggested improved
      explanations of the nature of the P-O bond.

PMID- 22987753
TI  - Back to the future: a new 'old' lead for tuberculosis.

PMID- 22987754
TI  - Organosilica-functionalized zeolitic imidazolate framework ZIF-90 membrane with
      high gas-separation performance.
AB  - A clear separation: A post-synthetic functionalization method is reported to
      obtain a highly permselective zeolitic imidazolate framework (ZIF-90) membrane.
      The intercrystalline defects of the ZIF-90 membrane are minimized to enhance the
      separation selectivity while a high permeance is maintained.

PMID- 22987757
TI  - The brain in the belly: what and how of fetal neuroimaging?
AB  - This work reviews magnetic resonance imaging in the developing human brain. It
      focuses on fetal brain imaged in vivo and in utero with complementary sections on
      abnormalities seen in clinical settings, and on potential of diffusion tensor
      imaging and of proton magnetic resonance spectroscopy. The main purposes are to
      illustrate the normal fetal developing brain and its abnormalities commonly
      encountered in utero, and to emphasize the potential role of adjunct techniques
      such as diffusion imaging and spectroscopy that may help elucidate fetal brain
      maturation and its abnormalities.

PMID- 22987758
TI  - Practical medical applications of quantitative MR relaxometry.
AB  - Conventional MR images are qualitative, and their signal intensity is dependent
      on several complementary contrast mechanisms that are manipulated by the MR
      hardware and software. In the absence of a quantitative metric for absolute
      interpretation of pixel signal intensities, one that is independent of scanner
      hardware and sequences, it is difficult to perform comparisons of MR images
      across subjects or longitudinally in the same subject. Quantitative relaxometry
      isolates the contributions of individual MR contrast mechanisms (T1, T2, T2) and
      provides maps, which are independent of the MR protocol and have a physical
      interpretation often expressed in absolute units. In addition to providing an
      unbiased metric for comparing MR scans, quantitative relaxometry uses the
      relationship between MR maps and physiology to provide a noninvasive surrogate
      for biopsy and histology. This study provides an overview of some promising
      clinical applications of quantitative relaxometry, followed by a description of
      the methods and challenges of acquiring accurate and precise quantitative MR
      maps. It concludes with three case studies of quantitative relaxometry applied to
      studying multiple sclerosis, liver iron, and acute myocardial infarction.

PMID- 22987756
TI  - Advances in musculoskeletal MRI: technical considerations.
AB  - The technology of musculoskeletal magnetic resonance imaging (MRI) is advancing
      at a dramatic rate. MRI is now done at medium and higher field strengths with
      more specialized surface coils and with more variable pulse sequences and
      postprocessing techniques than ever before. These innumerable technical advances
      are advantageous as they lead to an increased signal-to-noise ratio and increased
      variety of soft-tissue contrast options. However, at the same time they
      potentially produce more imaging artifacts when compared with past techniques.
      Substantial technical advances have considerable clinical challenges in
      musculoskeletal radiology such as postoperative patient imaging, cartilage
      mapping, and molecular imaging. In this review we consider technical advances in
      hardware and software of musculoskeletal MRI along with their clinical
      applications.

PMID- 22987755
TI  - Review of MR elastography applications and recent developments.
AB  - The technique of MR elastography (MRE) has emerged as a useful modality for
      quantitatively imaging the mechanical properties of soft tissues in vivo.
      Recently, MRE has been introduced as a clinical tool for evaluating chronic liver
      disease, but many other potential applications are being explored. These
      applications include measuring tissue changes associated with diseases of the
      liver, breast, brain, heart, and skeletal muscle including both focal lesions
      (e.g., hepatic, breast, and brain tumors) and diffuse diseases (e.g., fibrosis
      and multiple sclerosis). The purpose of this review article is to summarize some
      of the recent developments of MRE and to highlight some emerging applications.

PMID- 22987760
TI  - Predicting the enantioselectivity of the copper-catalysed cyclopropanation of
      alkenes by using quantitative quadrant-diagram representations of the catalysts.
AB  - We present a new methodology to predict the enantioselectivity of asymmetric
      catalysis based on quantitative quadrant-diagram representations of the catalysts
      and quantitative structure-selectivity relationship (QSSR) modelling. To account
      for quadrant occupation, we used two types of molecular steric descriptors: the
      Taft-Charton steric parameter (nu(Charton)) and the distance-weighted volume
      (V(W) ). By assigning the value of the steric descriptors to each of the
      positions of the quadrant diagram, we generated the independent variables to
      build the multidimensional QSSR models. The methodology was applied to predict
      the enantioselectivity in the cyclopropanation of styrene catalysed by copper
      complexes. The dataset comprised 30 chiral ligands belonging to four different
      oxazoline-based ligand families: bis- (Box), azabis- (AzaBox), quinolinyl-
      (Quinox) and pyridyl-oxazoline (Pyox). In the first-order approximation, we
      generated QSSR models with good predictive ability (r(2) =0.89 and q(2) =0.88).
      The derived stereochemical model indicated that placing very large groups at two
      diagonal quadrants and leaving free the other two might be enough to obtain an
      enantioselective catalyst. Fitting the data to a higher-order polynomial, which
      included crossterms between the descriptors of the quadrants, resulted in an
      improvement of the predicting ability of the QSSR model (r(2) =0.96 and q(2)
      =0.93). This suggests that the relationship between the steric hindrance and the
      enantioselectivity is non-linear, and that bulky substituents in diagonal
      quadrants operate synergistically. We believe that the quantitative quadrant
      diagram-based QSSR modelling is a further conceptual tool that can be used to
      predict the selectivity of chiral catalysts and other aspects of catalytic
      performance.

PMID- 22987761
TI  - Dysregulated expression of secretogranin III is involved in neurotoxin-induced
      dopaminergic neuron apoptosis.
AB  - The neurotoxins paraquat (PQ) and dopamine (DA or 6-OHDA) cause apoptosis of
      dopaminergic neurons in the substantia nigra pars compacta (SNpc), reproducing an
      important pathological feature of Parkinson's disease (PD). Secretogranin III
      (SCG3), a member of the multifunctional granin family, plays a key role in
      neurotransmitter storage and transport and in secretory granule biogenesis, which
      involves the uptake of exogenous toxins and endogenous "toxins" in neuroendocrine
      cells. However, the molecular mechanisms of neurotoxin-induced apoptosis in
      dopaminergic neurons and the role of SCG3-associated signaling pathways in
      neuroendocrine regulation are unclear. To address this, we used PQ- and DA
      induced apoptosis in SH-SY5Y human dopaminergic cells as an in vitro model to
      investigate the association between SCG3 expression level and apoptosis. SCG3 was
      highly expressed in SH-SY5Y cells, and SCG3 mRNA and protein levels were
      dramatically decreased after PQ treatment. Apoptosis induced by PQ is associated
      with caspase activation and decreased SCG3 expression, and restoration of SCG3
      expression is observed after treatment with caspase inhibitors. Overexpressed
      SCG3 in nonneuronal cells and endogenous SCG3 in SH-SY5Y cells are cleaved into
      specific fragments by recombinant caspase-3 and -7, but the fragments were not
      detected in PQ-treated SH-SY5Y cells. Therefore, SCG3 may be involved in
      apoptosis signal transduction as a caspase substrate, leading to loss of its
      original biological functions. In addition, SCG3 may be a pivotal component of
      the neuroendocrine pathway and play an important role in neuronal communication
      and neurotransmitter release, possibly representing a new potential target in the
      course of PD pathogenesis.

PMID- 22987762
TI  - Developing scaffolds for tissue engineering using the Ca2+-induced cold gelation
      by an experimental design approach.
AB  - The Ca(2+)-induced cold gelation technique was found suitable to prepare highly
      porous biodegradable scaffolds based on bovine serum albumin (BSA) and alpha
      casein from bovine milk for tissue engineering. A 2(3) full factorial design was
      used to study the influence and impact of each factor on the several responses of
      the scaffolds. In vitro degradation (ID), swelling ratio (SR), porosity (PO), and
      pore size (PS) as well cytotoxicity (CT) were evaluated and shown to be dependent
      on the pH of sample preparation and on the amount of BSA and casein present,
      making these scaffolds tunable structures. Under optimized working conditions
      (4.19% of BSA, 0.69% of Casein, pH 7.07), the ID attained was 37.97%, the SR
      observed was 11.87, the PO was 82.11%, the PS measured was 180.63 MUm at surface,
      and 175.91 MUm at fracture, whereas maximum cell viability was 84% in comparison
      to controls. Moreover, the scaffold supported cell adhesion and proliferation.
      These results, consistent with the prediction by the experimental design
      approach, support the use of this methodology to develop tunable scaffolds for
      tissue engineering using the Ca(2+)-induced cold gelation.

PMID- 22987763
TI  - Crystal structure of the Campylobacter jejuni Cj0090 protein reveals a novel
      variant of the immunoglobulin fold among bacterial lipoproteins.
AB  - Bacterial lipoproteins play an important role in bacterial pathogenesis and
      physiology. The genome of Campylobacter jejuni, a major foodborn pathogen, is
      predicted to contain over 20 lipoproteins. However, the functions of the majority
      of C. jejuni lipoproteins remain unknown. The Cj0090 protein is encoded by a
      lipoprotein operon composed of cj0089, cj0090, and cj0091. Here, we report the
      crystal structure of Cj0090 at 1.9 A resolution, revealing a novel variant of the
      immunoglobulin fold with beta-sandwich architecture. The structure suggests that
      Cj0090 may be involved in protein-protein interactions, consistent with a
      possible role for bacterial lipoproteins.

PMID- 22987764
TI  - [Screening of depression in primary care in Hungary and its importance in suicide
      prevention].
AB  - The current prevalence of DSM-IV depressive disorders were surveyed among 984
      primary care attendees in 6 PCPs in Hungary, using the Beck Depression Inventory
      (BDI) and the PRIME-MD screening instrument. The current prevalence rate of any
      DSM-IV depressive disorders, including symptomatic major depressive episode (MDE)
      were 18.5% and 7.3% respectively. BDI identified any current depressive disorders
      with 95% sensitivity and 56% specificity and the same figures for MDE were 83%
      and 23%, respectively. Current MDE was found 50% of patients with positive family
      history of suicide, comparing to the 14.3% of those without. The BDI and the
      PRIME-MD are useful screening tools for detecting depressive disorders in PCPs.
      Family history of completed suicide as a clinical marker could improve suicide
      prevention through the more effective management of MDE in primary care.

PMID- 22987765
TI  - [Integrative approach in the psychotherapy of borderline personality disorder].
AB  - In the last 20 years six psychotherapy methods have been developed specifically
      for borderline personality disorder. Solid RCT evidences suggests the efficacy of
      all the methods. Roughly equivalent improvement was obtained from the different
      types of psychotherapies. Today we have reached a new phase of the borderline
      "psychotherapy boom", the integrative approach. According to the integrative
      treatment advocates we should not choose among these effective treatments but we
      can incorporate in the therapy all the components that work. The integrative
      approach uses general factors common to all effective therapies, combined with
      specific treatment techniques taken from different therapies in order to treat
      the given patient's psychopathology. These common factors are: coherent
      framework; attention to strategies for building strong positive alliance and
      maintaining patient motivation; creating a safe and structured therapeutic
      environment; clear treatment frame; transparency of the goals and roles; focus
      upon presenting problems; higher level therapeutic activity; here-and-now focus;
      and facilitating self-reflection. Treatment focuses on change while maintaining a
      validating and supportive stance. General strategies can be supplemented by more
      specific techniques such as cognitive-behavioral interventions for reducing
      maladaptive behavior, training for developing emotion regulation skills and
      interpersonal skills coming from dialectical behavior therapy. Methods drawn from
      psychodynamic approaches can be used for the modification of underlying
      interpersonal cognitive-emotional schemas.

PMID- 22987767
TI  - [Be in role. Examination of dissociative experiences of theatrical actors].
AB  - INTRODUCTION: In spite of the fact that acting makes great demands on the
      personality, there is lack of research dealing with the psychological status of
      actors. Resulted from their profession actors often experience dissociation,
      since absorption and changing of their identity is a routine task for them. They
      are acting on the stage, and they are acting in private. METHOD: 36 theatrical
      actors completed the DISQ-H version of the Dissociation Questionnaire measuring
      four subscales: Identity Confusion, Amnesia, Loss of Control and Absorption. In
      order to understand their experiences deeper, nine actors were interviewed. The
      sample consisted of 21 men and 15 women and their ages ranged from 23 to 60.
      Higher ages implied longer career as an actor, thus the youngest subject had been
      working for 2 years, while the oldest one had been working for 39 years. RESULTS:
      DISQ-H total score results of the actors were significantly higher compared to
      the Hungarian standard scores. As we expected, the two non-pathological subscales
      (Loss of Control and Absorption) showed significant differences compared to the
      standard scores of the subscales. In the case of Identity Confusion subscale we
      found no significant differences, however the results indicate that the tendency
      observed emphasizes the importance of further research of this phenomenon.
      CONCLUSION: To sum up, dissociative experiences proved to be important elements
      of acting.

PMID- 22987766
TI  - [Hungarian version of the Impact of Event Scale. Psychometric evaluation].
AB  - BACKGROUND: The Impact of Event Scale (IES, Horowitz, 1979) has been widely used
      to evaluate subjective stress following traumatic life events. Based on the
      theoretical reflections of the authors, it consists of two subscales: intrusion
      and avoidance. Although the empirical data of the past 30 years have supported
      the original two-factor model to a large extent, alternative models have also
      been published. Our aim was to evaluate the psychometric properties of the Impact
      of Event Scale Hungarian version. METHODS: Data from 244 undergraduate students
      on the Hungarian version of Impact of Event Scale (Annus, Perczel Forintos, Kiss,
      2005) were analyzed. Subjects were asked to fill in Beck Depression Inventory
      shortened version (Beck & Beck, 1972, Kopp & Forizs, 1993) and STAI-T
      (Spielberger, 1970, Sipos & Sipos, 1978) too. RESULTS: Internal consistency of
      the whole IES (Cronbach's a=0,891) as well as of intrusion (Cronbach's a=0,874)
      and avoidance (Cronbach's a=0,818) was found to be very good. Test-retest
      reliability of the whole scale (r=0,491, p<0,001) as well as of subscales (for
      intrusion r=0,543 p<0,001, for avoidance r=0,523 p<0,001) was satisfactory. No
      association was found between gender and IES scores. Confirmatory and explanatory
      factor analysis supported the two factor model in our sample. IES had a moderate
      positive correlation with depression (r=0,273, p<0,001) and anxiety (r=0,381,
      p<0,001), indicating that it reflects a somewhat related but still independent
      construct. CONCLUSIONS: The Hungarian version of the Impact of Event Scale has
      been proved a valid and reliable measure of post-traumatic stress symptoms.

PMID- 22987768
TI  - [Psychosomatic approach to ulcerative colitis, a survey of its psychological
      characteristics -- viewpoint of the clinical psychologist].
AB  - INTRODUCTION: Provides a short overview of the basics of psychosomatic approach.
      THEORETICAL BACKGROUND: Introduces ulcerative colitis (UC) in psychosomatic
      bibliography, its psychodynamic, behavioral and systemic approach, which is less
      investigated than irritable bowel syndrome. Describes picture of
      'colitispersonality' and possible psychotherapeutic treatments found in
      bibliography. Later these psychological characteristics are investigated
      empirically. METHODS: 21 patients with ulcerative colitis and 21 healthy controls
      are compared by Hungarian versions of the Toronto Alaexithymia Scale (TAS-20),
      Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Parental Bonding
      Instrument (PBI) and the Ways of Coping Questionnaire (WCQ). RESULTS: UC patients
      can be described by higher measures of alexithymia (p<0.05), depression (p<0.05),
      and anxiety (p<0.05) than controls. Parental Bonding Instrument showed patients'
      higher level of 'overprotection' (p<.05), and lower of experienced 'restriction'
      (p<0.05). According to the WCQ patients show significant difference from healthy
      controls in ways of coping: have lower measures of 'problem-analyzing' (p<0.05),
      are less likely to 'seek social support' (p<0.05), and tend to show less
      'purposeful action' (p=0.07). CONCLUSIONS: Results showed, that there is at least
      a group of UC patients who may have the personality traits and psychological
      problems of the 'psychosomatic syndrome', and in their case psychological
      intervention, help would be relevant. This small-sample survey can be regarded as
      a presearch, and indicates the importance and necessity of further comprehensive
      investigation of UC patients' psychological characteristics.

PMID- 22987769
TI  - [Cancer as psychological trauma and its effects on positive illusions].
AB  - Cancer as a psychological trauma can result in development of psychopathological
      disorders (e.g. depression), and also positive changes experienced in numerous
      domains of life (e.g. greater appreciation of life). Cognitivists tried to
      explain the potential traumatic impact of the adversities with the phenomenon
      that most of the people's world concepts are full of positive illusions and they
      mostly lack the idea that tragedies can occur also with them. However, this naive
      worldview can be altered by a trauma in a negative way. Moreover, according to
      the theory of cognitive adaptation certain positive illusions (perception of
      personal control, self-enhancement, unrealistic optimism, search for meaning)
      become even more activated by traumatic life events helping the adjustment to the
      adversity. More recently, researches have succeeded in proving the role of
      positive illusions in maintaining mental and physical health. The aim of the
      present study is to review the potential psychological consequences of cancer as
      a trauma and to display the schema-changes of trauma victims through the
      phenomenon of positive illusions.

PMID- 22987770
TI  - Central nervous system malformations and deformations in FGFR2-related
      craniosynostosis.
AB  - Central nervous system anomalies in Pfeiffer syndrome (PS) due to mutations in
      the FGFR2 gene are poorly understood, even though PS is often associated with
      serious cognitive impairment. The aim of this study is to describe the
      neuropathological phenotype in PS. We present four severe fetal cases of sporadic
      PS with FGFR2 mutations who underwent termination followed by fetopathological
      and neuropathological examination. We studied the expression pattern of Fgfr2 in
      the mouse brain using radioactive fluorescence in situ hybridization. PS is
      associated with brain deformations due to the abnormal skull shape, but FGFR2
      mutations also induce specific brain developmental anomalies: megalencephaly,
      midline disorders, amygdala, and hippocampus malformations, and ventricular wall
      alterations. The expression pattern of Fgfr2 in mice matches the distribution of
      malformations in humans. The brain anomalies in PS result from the combination of
      mechanical deformations and intrinsic developmental disorders due to FGFR2
      hyperactivity. Several similarities are noted between these anomalies and the
      brain lesions observed in other syndromes due to mutations in FGF-receptor genes.
      The specific involvement of the hippocampus and the amygdala should encourage the
      precise cognitive screening of patients with mild forms of PS.

PMID- 22987771
TI  - Growth factor regulation of intracellular pH homeostasis under hypoxic conditions
      in isolated equine articular chondrocytes.
AB  - Hypoxia and acidosis are recognized features of inflammatory arthroses. This
      study describes the effects of IGF-1 and TGF-beta(1) on pH regulatory mechanisms
      in articular cartilage under hypoxic conditions. Acid efflux, reactive oxygen
      species (ROS), and mitochondrial membrane potential were measured in equine
      articular chondrocytes isolated in the presence of serum (10% fetal calf serum),
      IGF-1 (1, 10, 50, 100 ng/ml) or TGF-beta(1) (0.1, 1, 10 ng/ml) and then exposed
      to a short-term (3 h) hypoxic insult (1% O(2)). Serum and 100 ng/ml IGF-1 but not
      TGF-beta(1) attenuated hypoxic regulation of pH homeostasis. IGF-1 appeared to
      act through mitochondrial membrane potential stabilization and maintenance of
      intracellular ROS levels in very low levels of oxygen. Using protein
      phosphorylation inhibitors PD98059 (25 uM) and wortmannin (200 nM) and Western
      blotting, ERK1/2 and PI-3 kinase pathways are important for the effect of IGF-1
      downstream to ROS generation in normoxia but only PI-3 kinase is implicated in
      hypoxia. These results show that oxygen and growth factors interact to regulate
      pH recovery in articular chondrocytes by modulating intracellular oxygen
      metabolites.

PMID- 22987772
TI  - Photoluminescence properties and energy transfer in Ce(3+) /Dy(3+) co-doped Sr(3)
      MgSi(2) O(8) phosphors for potential application in ultraviolet white light
      emitting diodes.
AB  - Sr(3) MgSi(2) O(8) :Ce(3+) , Dy(3+) phosphors were prepared by a solid-state
      reaction technique and the photoluminescence properties were investigated. The
      emission spectra show not only a band due to Ce(3+) ions (403 nm) but also as a
      band due to Dy(3+) ions (480, 575 nm) (UV light excitation). The
      photoluminescence properties reveal that effective energy transfer occurs in
      Ce(3+) /Dy(3+) co-doped Sr(3) MgSi(2) O(8)phosphors, and the co-doping of Ce(3+)
      could enhance the emission intensity of Dy(3+) to a certain extent by
      transferring its energy to Dy(3+) . The Ce(3+) /Dy(3+) energy transfer was
      investigated by emission/excitation spectra, and photoluminescence decay
      behaviors. In Sr2.94 MgSi2 O8 :0.01Ce(3+) , 0.05Dy(3+) phosphors, the
      fluorescence lifetime of Dy(3+) (from 3.35 to 27.59 ns) is increased whereas that
      of Ce(3+) is greatly decreased (from 43.59 to 13.55 ns), and this provides
      indirect evidence of the Ce(3+) to Dy(3+) energy transfer. The varied emitted
      color of Sr(3) MgSi(2) O(8):Ce(3+) , Dy(3+) phosphors from blue to white were
      achieved by altering the concentration ratio of Ce(3+) and Dy(3+) . These results
      indicate Sr(3) MgSi(2) O(8):Ce(3+) , Dy(3+) may be as a candidate phosphor for
      white light-emitting diodes.

PMID- 22987773
TI  - Why do women have more children than they want? Understanding differences in
      women's ideal and actual family size in a natural fertility population.
AB  - OBJECTIVES: We develop and test a conceptual model of factors influencing women's
      ideal family size (IFS) in a natural fertility population, the Tsimane of
      Bolivia. The model posits affects of socioecology, reproductive history, maternal
      condition, and men's IFS. We test three hypotheses for why women may exceed their
      IFS despite experiencing socioeconomic development: (H(1) ) limited autonomy;
      (H(2) ) improved maternal condition; and (H(3) ) low returns on investments in
      embodied capital. METHODS: Women's reproductive histories and prospective
      fertility data were collected from 2002 to 2008 (n = 305 women). Semistructured
      interviews were conducted with Tsimane women to study the perceived value of
      parental investment (n = 76). Multiple regression, t-tests, and analysis of
      variance (ANOVA) are used to test model predictions. RESULTS: Women's IFS is
      predicted by their socioecology, reproductive history, maternal condition, and
      husband's IFS. Hypotheses 2 and 3 are supported. Couples residing near town have
      smaller IFS (women = 3.75 +/- 1.64; men = 3.87 +/- 2.64) and less variance in
      IFS. However, the degree fertility exceeds IFS is inversely correlated with
      distance to town (Partial r = -0.189, df = 156, P = 0.018). Women living near
      town have greater maternal condition but 64% value traditional skills over formal
      schooling and 88% believe living in town is unfeasible. CONCLUSIONS: While
      reduced IFS is evident with socioeconomic development, fertility decline may not
      immediately follow. When perceived benefits of investment in novel forms of
      embodied capital are low, and somatic wealth and large kin networks persist as
      important components of fitness, fertility may remain high and increase if
      maternal condition improves.

PMID- 22987775
TI  - Reply: To PMID 21953442.

PMID- 22987774
TI  - Functional connectivity evidence of cortico-cortico inhibition in temporal lobe
      epilepsy.
AB  - Epileptic seizures can initiate a neural circuit and lead to aberrant neural
      communication with brain areas outside the epileptogenic region. We focus on
      interictal activity in focal temporal lobe epilepsy and evaluate functional
      connectivity (FC) differences that emerge as function of bilateral versus
      strictly unilateral epileptiform activity. We assess the strength of FC at rest
      between the ictal and non-ictal temporal lobes, in addition to whole brain
      connectivity with the ictal temporal lobe. Results revealed strong connectivity
      between the temporal lobes for both patient groups, but this did not vary as a
      function of unilateral versus bilateral interictal status. Both the left and
      right unilateral temporal lobe groups showed significant anti-correlated activity
      in regions outside the epileptogenic temporal lobe, primarily involving the
      contralateral (non-ictal/non-pathologic) hemisphere, with precuneus involvement
      prominent. The bilateral groups did not show this contralateral anti-correlated
      activity. This anti-correlated connectivity may represent a form of protective
      and adaptive inhibition, helping to constrain epileptiform activity to the
      pathologic temporal lobe. The absence of this activity in the bilateral groups
      may be indicative of flawed inhibitory mechanisms, helping to explain their more
      widespread epileptiform activity. Our data suggest that the location and build up
      of epilepsy networks in the brain are not truly random, and are not limited to
      the formation of strictly epileptogenic networks. Functional networks may develop
      to take advantage of the regulatory function of structures such as the precuneus
      to instantiate an anti-correlated network, generating protective cortico-cortico
      inhibition for the purpose of limiting seizure spread or epileptogenesis.

PMID- 22987776
TI  - A competitive strategy coupled with endonuclease-assisted target recycling for
      DNA detection using silver-nanoparticle-tagged carbon nanospheres as labels.
AB  - A simple competitive strategy was designed for the sensitive detection of
      sequence-specific DNA by combining endonuclease-assisted target recycling and
      electrochemical stripping analysis of silver nanoparticles (AgNPs). The AgNP
      tagged carbon nanospheres were synthesized by means of in situ reduction of Ag(+)
      adsorbed onto a negatively charged polyelectrolyte layer and functionalized with
      streptavidin for binding biotin-labeled DNA strands. The labeled strand was
      captured on the DNA sensor surface by competitive hybridization of biotinated
      primer 1 and its cleaved product. The cleaved product could be amplified in
      homogeneous solution by endonuclease-assisted target recycling with a Y-shaped
      junction DNA structure, thus leading to the correlation of the stripping signal
      to the target concentration. The functionalized nanosphere was characterized with
      X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission
      electron microscopy. The proposed method showed a linear range from 0.1 to 1000
      fM with a limit of detection of 0.066 fM (3sigma) and good selectivity for base
      discrimination. The designed strategy provided a sensitive tool for DNA analysis
      and could be widely applied in bioanalysis and biomedicine.

PMID- 22987777
TI  - Gamma ray treatment enhances bioactivity and osseointegration capability of
      titanium.
AB  - The time-dependent degradation of titanium bioactivity (i.e., the biological
      aging of titanium) has been reported in previous studies. This phenomenon is
      caused by the loss of hydrophilicity and the inevitable occurrence of progressive
      contamination of titanium surfaces by hydrocarbons. In this study, we tested the
      hypothesis that gamma ray treatment, owing to its high energy to decompose and
      remove organic contaminants, enhances the bioactivity and osteoconductivity of
      titanium. Titanium disks were acid-etched and stored for 4 weeks. Rat bone marrow
      derived osteoblasts (BMOs) were cultured on titanium disks with or without gamma
      ray treatment (30 kGy) immediately before experiments. The cell density at day 2
      increased by 50% on gamma-treated surfaces, which reflected the 25% higher rate
      of cell proliferation. Osteoblasts on gamma-treated surfaces showed 30% higher
      alkaline phosphatase activity at day 5 and 60% higher calcium deposition at day
      20. The strength of in vivo bone-implant integration increased by 40% at the
      early healing stage of week 2 for gamma-treated implants. Gamma ray-treated
      surfaces regained hydrophilicity and showed a lower percentage of carbon (35%) as
      opposed to 48% on untreated aged surfaces. The data indicated that gamma ray
      pretreatment of titanium substantially enhances its bioactivity and
      osteoconductivity, in association with the significant reduction in surface
      carbon and the recovery of hydrophilicity. The results suggest that gamma ray
      treatment could be an effective surface enhancement technology to overcome
      biological aging of titanium and improve the biological properties of titanium
      implants.

PMID- 22987778
TI  - Staphylococcal display for combinatorial protein engineering of a head-to-tail
      affibody dimer binding the Alzheimer amyloid-beta peptide.
AB  - We have previously generated an affibody molecule for the disease-associated
      amyloid beta (Abeta) peptide, which has been shown to inhibit the formation of
      various Abeta aggregates and revert the neurotoxicity of Abeta in a fruit fly
      model of Alzheimer's disease. In this study, we have investigated a new bacterial
      display system for combinatorial protein engineering of the Abeta-binder as a
      head-to-tail dimeric construct for future optimization efforts, e.g. affinity
      maturation. Using the bacterial display platform, we have: (i) demonstrated
      functional expression of the dimeric binder on the cell surface, (ii) determined
      the affinity and investigated the pH sensitivity of the interaction, (iii)
      demonstrated the importance of an intramolecular disulfide bond through
      selections from a cell-displayed combinatorial library, as well as (iv)
      investigated the effects from rational truncation of the N-terminal part of the
      affibody molecule on surface expression level and Abeta binding. Overall, the
      detailed engineering and characterization of this promising Abeta-specific
      affibody molecule have yielded valuable insights concerning its unusual binding
      mechanism. The results also demonstrated that our bacterial display system is a
      suitable technology for future protein engineering and characterization efforts
      of homo- or heterodimeric affinity proteins.

PMID- 22987779
TI  - Self-healing supramolecular block copolymers.
AB  - Polymer, heal thyself! Supramolecular ABA triblock copolymers formed by
      dimerization of 2-ureido-4-pyrimidinone (UPy) end-functionalized polystyrene-b
      poly(n-butyl acrylate) (PS-b-PBA) AB diblock copolymers have been synthesized,
      resulting in a self-healing material that combines the advantageous mechanical
      properties of thermoplastic elastomers and the dynamic self-healing features of
      supramolecular materials.

PMID- 22987781
TI  - Characterization of plasma beta-secretase (BACE1) activity and soluble amyloid
      precursor proteins as potential biomarkers for Alzheimer's disease.
AB  - Reduction in cerebrospinal fluid (CSF) amyloid beta42 (Abeta42) and elevation in
      total tau and phospho-thr181 tau consistently differentiate between Alzheimer's
      disease (AD) and age-matched control subjects. In contrast, CSF beta-site APP
      cleaving enzyme activity (BACE1) and soluble amyloid precursor proteins alpha and
      beta (sAPPalpha and sAPPbeta) are without consistent patterns in AD subjects.
      Plasma sampling is much easier, with fewer side effects, and is readily applied
      in primary care centers, so we have developed and validated novel plasma BACE
      activity, sAPPbeta, and sAPPalpha assays and investigated their ability to
      distinguish AD from age-matched controls. Plasma BACE activity assay was
      sensitive and specific, with signal being immunodepleted with a specific BACE1
      antibody and inhibited with a BACE1-specific inhibitor. Plasma sAPPbeta and
      sAPPalpha assays were specific, with signal diluting linearly, immunodepleted
      with specific antibodies, and at background levels in APP knockout mice. In
      rhesus monkeys, BACE1 but not gamma-secretase inhibitor led to significant
      lowering of plasma sAPPbeta with concurrent elevation of plasma sAPPalpha. AD
      subjects showed a significant increase in plasma BACE1 activity, sAPPbeta,
      sAPPalpha, and Abeta42 (P < 0.001) compared with age-matched controls. In
      conclusion, plasma BACE activity and sAPP endpoints provide novel investigative
      biomarkers for AD diagnosis and potential pharmacodynamic biomarkers for
      secretase inhibitor studies.

PMID- 22987783
TI  - Recurrence of osteogenesis imperfecta due to maternal mosaicism of a novel COL1A1
      mutation.

PMID- 22987782
TI  - Crystal structure and nucleic acid-binding activity of the CRISPR-associated
      protein Csx1 of Pyrococcus furiosus.
AB  - In many prokaryotic organisms, chromosomal loci known as clustered regularly
      interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (CAS) genes
      comprise an acquired immune defense system against invading phages and plasmids.
      Although many different Cas protein families have been identified, the exact
      biochemical functions of most of their constituents remain to be determined. In
      this study, we report the crystal structure of PF1127, a Cas protein of
      Pyrococcus furiosus DSM 3638 that is composed of 480 amino acids and belongs to
      the Csx1 family. The C-terminal domain of PF1127 has a unique beta-hairpin
      structure that protrudes out of an alpha-helix and contains several positively
      charged residues. We demonstrate that PF1127 binds double-stranded DNA and RNA
      and that this activity requires an intact beta-hairpin and involve the
      homodimerization of the protein. In contrast, another Csx1 protein from
      Sulfolobus solfataricus P2 that is composed of 377 amino acids does not have the
      beta-hairpin structure and exhibits no DNA-binding properties under the same
      experimental conditions. Notably, the C-terminal domain of these two Csx1
      proteins is greatly diversified, in contrast to the conserved N-terminal domain,
      which appears to play a common role in the homodimerization of the protein. Thus,
      although P. furiosus Csx1 is identified as a nucleic acid-binding protein, other
      Csx1 proteins are predicted to exhibit different individual biochemical
      activities.

PMID- 22987784
TI  - Motion artifact reduction of diffusion-weighted MRI of the liver: use of velocity
      compensated diffusion gradients combined with tetrahedral gradients.
AB  - PURPOSE: To assess the effect of motion artifact reduction on the diffusion
      weighted magnetic resonance imaging (DWI-MRI) of the liver, we compared velocity
      compensated DWI (VC-DWI) and VC-DWI combined with tetrahedral gradients (t-VC
      DWI) to conventional DWI (c-DWI) in the assessment of apparent diffusion
      coefficients (ADCs) of the liver. MATERIALS AND METHODS: In 12 healthy
      volunteers, the liver was scanned with c-DWI, VC-DWI, and t-VC-DWI sequences. The
      signal-to-noise ratio (SNR) and ADC of the liver parenchyma were measured and
      compared among sequences. RESULTS: The image quality was visually better for t-VC
      DWI than for the others. The SNR for t-VC-DWI was significantly higher than that
      for VC-DWI (P < 0.05) and comparable to that for c-DWI. ADCs in both hepatic
      lobes were significantly lower for t-VC-DWI than for c-DWI (P < 0.01). ADC in the
      left lobe was significantly lower for VC-DWI than for c-DWI (P < 0.01). Although
      ADC in the left lobe was significantly higher for c-DWI (P < 0.01), no
      significant differences in ADCs were found between the right and left lobes for
      VC-DWI and t-VC-DWI. CONCLUSION: The use of a t-VC-DWI sequence enables us to
      correct ADCs of the liver for artificial elevation due to cardiac motion, with
      preserved SNR.

PMID- 22987780
TI  - The cellular and synaptic location of activated TrkB in mouse hippocampus during
      limbic epileptogenesis.
AB  - Understanding the mechanisms of limbic epileptogenesis in cellular and molecular
      terms may provide novel therapeutic targets for its prevention. The neurotrophin
      receptor tropomyosin-related kinase B (TrkB) is thought to be critical for limbic
      epileptogenesis. Enhanced activation of TrkB, revealed by immunodetection of
      enhanced phosphorylated TrkB (pTrkB), a surrogate measure of its activation, has
      been identified within the hippocampus in multiple animal models. Knowledge of
      the cellular locale of activated TrkB is necessary to elucidate its functional
      consequences. Using an antibody selective to pTrkB in conjunction with confocal
      microscopy and cellular markers, we determined the cellular and subcellular
      locale of enhanced pTrkB induced by status epilepticus (SE) evoked by infusion of
      kainic acid into the amygdala of adult mice. SE induced enhanced pTrkB
      immunoreactivity in two distinct populations of principal neurons within the
      hippocampus-the dentate granule cells and CA1 pyramidal cells. Enhanced
      immunoreactivity within granule cells was found within mossy fiber axons and
      giant synaptic boutons. By contrast, enhanced immunoreactivity was found within
      apical dendritic shafts and spines of CA1 pyramidal cells. A common feature of
      this enhanced pTrkB at these cellular locales is its localization to excitatory
      synapses between excitatory neurons, presynaptically in the granule cells and
      postsynaptically in CA1 pyramidal cells. Long-term potentiation (LTP) is one
      cellular consequence of TrkB activation at these excitatory synapses that may
      promote epileptogenesis.

PMID- 22987785
TI  - Price and tax measures and illicit trade in the framework convention on tobacco
      control: what we know and what research is required.
AB  - INTRODUCTION: Article 6 of the Framework Convention on Tobacco Control commits
      Parties to use tax and price policies to reduce tobacco use, whereas Article 15
      commits Parties to implement measures to eliminate the illicit trade in tobacco
      products. This paper identifies research gaps/needs, especially in low- and
      middle-income countries, which, if adequately addressed, would help in
      implementing Articles 6 and 15. METHODS: Based on a recent comprehensive review
      on the impact of tax and price on tobacco consumption and a summary of reviews
      and narratives about the illicit tobacco market, research gaps are identified.
      RESULTS: Countries have highly diverse research needs, depending on the stage of
      the tobacco epidemic, previous research and data availability, and making a
      ranking of research needs infeasible. Broad issues for further research are the
      following: (1) monitoring tobacco consumption, prices, and taxes, (2) assessing
      the effectiveness of the tax structure in generating revenue and reducing tobacco
      use, (3) strengthening the tax administration system in order to reduce tax
      evasion and tax avoidance, (4) improving our understanding of the political
      economy of tobacco tax policy, and (5) employing a multidisciplinary approach to
      assessing the magnitude of illicit tobacco trade. CONCLUSIONS: At a technical
      level, the case for increasing excise taxes to improve public health and increase
      government revenue is easily made, but the political and policy environment is
      often not supportive. In order to effectively impact policy, the required
      approach would typically make use of rigorous economic techniques, and be
      cognizant of the political economy of raising excise taxes.

PMID- 22987786
TI  - Effects of brief mindfulness instructions on reactions to body image stimuli
      among female smokers: an experimental study.
AB  - INTRODUCTION: Recent research has shown that body image stimuli increase negative
      affect and smoking urges among female smokers. Mindfulness (paying attention to
      present-moment experience with an attitude of nonjudgmental acceptance) may be a
      useful technique to minimize the influence of body dissatisfaction on negative
      affect, smoking urges, and smoking behavior. METHODS: This study investigated
      whether mindfulness influences how female college smokers respond to a body image
      challenge. The study used a 2 * 2 factorial design with body image challenge
      (trying on a bathing suit vs. looking at a purse) crossed with instructions
      (mindfulness vs. silence). Female smokers (n = 64; M (age) = 20.03 [+/- 1.77],
      87.5% Caucasian) were randomly assigned to one of four conditions: Purse +
      Silence (n = 16), Body Image + Silence (n = 15), Purse + Mindfulness (n = 15),
      and Body Image + Mindfulness (n = 18).

PMID- 22987787
TI  - Toward a rational management of very early hepatocellular carcinoma.

PMID- 22987788
TI  - Spectrofluorimetric method for the determination of sulpiride in pharmaceutical
      preparations and human plasma through derivatization with 2-cyanoacetamide.
AB  - A sensitive and accurate spectrofluorimetric method has been developed for the
      determination of sulpiride in pharmaceutical preparations and human plasma. The
      developed method is based on the derivatization reaction of 2-cyanoacetamide with
      sulpiride in 30% ammonical solution. The fluorescent derivatized reaction product
      exhibited maximum fluorescence intensity at 379 nm after excitation at 330 nm.
      The optimum conditions for derivatization reactions were studied and the
      fluorescence intensity versus concentration plot was found to be linear over the
      concentration range 0.2-20.0 ug/mL with a correlation coefficient of 0.9985. The
      limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.82
      and 2.73 ng/mL, respectively. The proposed method was validated according to ICH
      guidelines. The effects of common excipients and co-administered drugs were also
      studied. The accuracy of the method was checked using the standard addition
      method and percent recoveries were found to be in the range of 99.00-101.25% for
      pharmaceutical preparations and 97.00-97.80% for spiked human plasma. The method
      was successfully applied to commercial formulations and the results obtained for
      the proposed method were compared with a high-performance liquid chromatography
      reference method and statistically evaluated using the Student's t-test for
      accuracy and the variance ratio F-test for precision. A reaction pathway was also
      proposed.

PMID- 22987789
TI  - Osteocutaneous radial forearm reconstruction of large partial cricotracheal
      defects.
AB  - BACKGROUND: Single-stage procedures for reconstruction of large cricotracheal
      defects have been limited in success and malignant immature teratomas in the
      larynx of an adult have never been reported. METHODS AND RESULTS: This was a case
      report and literature review. A 27-year-old man presented with 2 weeks of new
      onset stridor and was found to have a mass obstructing 80% of the subglottis and
      trachea. He underwent a noncircumferential partial cricotracheal resection with a
      resultant 7-cm luminal defect, followed by osteocutaneous radial forearm flap
      semi-rigid reconstruction. A novel technique was used to allow a functional and
      patent airway, which may be applied to other partial luminal reconstructive
      defects. Postoperatively, the patient was decannulated and has good speech
      quality and swallowing function. This work was performed at the Henry Ford Health
      System. This project was reviewed and was granted full approval by the Henry Ford
      Health System Institutional Review Board. CONCLUSIONS: This is the first reported
      case of malignant immature teratoma to involve the larynx, trachea, and recurrent
      laryngeal nerve in an adult patient, and the first single-stage technique
      described to use free tissue transfer without prefabrication for a 7-cm airway
      defect.

PMID- 22987790
TI  - Brain network of semantic integration in sentence reading: insights from
      independent component analysis and graph theoretical analysis.
AB  - A set of cortical and sub-cortical brain structures has been linked with sentence
      level semantic processes. However, it remains unclear how these brain regions are
      organized to support the semantic integration of a word into sentential context.
      To look into this issue, we conducted a functional magnetic resonance imaging
      (fMRI) study that required participants to silently read sentences with
      semantically congruent or incongruent endings and analyzed the network properties
      of the brain with two approaches, independent component analysis (ICA) and graph
      theoretical analysis (GTA). The GTA suggested that the whole-brain network is
      topologically stable across conditions. The ICA revealed a network comprising the
      supplementary motor area (SMA), left inferior frontal gyrus, left middle temporal
      gyrus, left caudate nucleus, and left angular gyrus, which was modulated by the
      incongruity of sentence ending. Furthermore, the GTA specified that the
      connections between the left SMA and left caudate nucleus as well as that between
      the left caudate nucleus and right thalamus were stronger in response to
      incongruent vs. congruent endings.

PMID- 22987791
TI  - Synthesis and structure-activity relationships of lansine analogues as
      antileishmanial agents.
AB  - Clear and rational thinking: A series of rationally designed, lansine-derived
      carbazoles was synthesized and evaluated for activity against promastigotes and
      amastigotes of Leishmania donovani, the causative agent of leishmaniasis. Some
      structural modifications gave rise to compounds with enhanced activity and
      selectivity over lansine, allowing structure-activity relationships to be
      elucidated and providing a foundation for the further development of this
      pharmacophore. 

PMID- 22987792
TI  - Evaluation of silver-containing activated carbon fiber for wound healing study:
      In vitro and in vivo.
AB  - Silver has antiseptic properties, anti-inflammatory properties, and is a broad
      spectrum antibiotic for multidrug-resistant strains of bacteria. The commercially
      available product, Silverlon(r), is a silver-plated three-dimensional polyamide
      fabric with a high silver concentration of 546 mg/100 cm(2). Thus, fibroblast
      cell growth is affected when exposed to the Silverlon(r) treated cell medium. Our
      study produced an activated carbon fiber wound dressing that incorporated various
      silver concentrations (in cooperation of Bio-Medical Carbon Technology) to
      examine antimicrobial properties and determine fibroblast cell viability upon
      exposure to the silver impregnated dressing material as compared to other
      commercially available products such as calcium alginate dressing, Sorbalgon(r),
      and silver-polyamide fabric dressing, Silverlon(r). The silver impregnated
      activated carbon fiber dressing induced less damage to fibroblast cells compared
      to the effect produced by Silverlon(r) and exhibited similar antibacterial
      abilities in vitro. An in vivo analysis showed that various silver concentrations
      impregnated activated carbon fiber dressings promoted tissue reconstruction for
      wound healing in rats with Pseudomonas aeruginosa infected wounds.

PMID- 22987793
TI  - Reservations in accepting that there is "depletion of bone marrow progenitor
      cells with aging." Generalization should be avoided.

PMID- 22987794
TI  - Physical activity increases gains in and prevents loss of physical function:
      results from the lifestyle interventions and independence for elders pilot study.
AB  - BACKGROUND: Physical activity (PA) appears to have a positive effect on physical
      function, however, studies have not examined multiple indices of physical
      function jointly nor have they conceptualized physical functioning as a state
      rather than a trait. METHODS: About 424 men and women aged 70-89 were randomly
      assigned to complete a PA or a successful aging (SA) education program. Balance,
      gait speed, chair stand performance, grip strength, and time to complete the 400
      m walk were assessed at baseline and at 6 and 12 months. Using hidden Markov
      model, empiric states of physical functioning were derived based on these
      performance measures of balance, strength, and mobility. Rates of gain and loss
      in physical function were compared between PA and SA. RESULTS: Eight states of
      disability were identified and condensed into four clinically relevant states.
      State 1 represented mild disability with physical functioning, states 2 and 3
      were considered intermediate states of disability, and state 4 severe disability.
      About 30.1% of all participants changed states at 6 months, 24.1% at 12 months,
      and 11.0% at both time points. The PA group was more likely to regain or sustain
      functioning and less likely to lose functioning when compared with SA. For
      example, PA participants were 20% more likely than the SA participants to remain
      in state 1. CONCLUSION: PA appears to have a favorable effect on the dynamics of
      physical functioning in older adults.

PMID- 22987795
TI  - Associations between arterial elasticity and markers of inflammation in healthy
      older women.
AB  - The purpose of this investigation was to examine the associations between
      circulating markers of inflammation and arterial elasticity in healthy older
      women. Participants were 50 women older than 60 years of age, body mass index 27
      +/- 4, and physically untrained. Large artery elasticity, small artery
      elasticity, systemic vascular resistance, total vascular impedance, estimated
      cardiac output, and estimated cardiac index were determined using pulse contour
      analysis. Serum concentrations of tumor necrosis factor-alpha, C-reactive protein
      (CRP), and interleukin 6 were assessed. Results from Pearson's correlation
      revealed that tumor necrosis factor-alpha was inversely associated with large
      artery elasticity (-.426, p < .01) and estimated cardiac index (-.324, p < .05)
      and positively associated with systemic vascular resistance (.386, p < .01) and
      total vascular impedance (.416, p < .01). Additionally, C-reactive protein was
      inversely associated with large artery elasticity (-.308, p < .01). The overall
      implication was that tumor necrosis factor-alpha and C-reactive protein appear to
      be critical inflammatory cytokines associated with reductions in arterial
      elasticity in older women.

PMID- 22987796
TI  - Using timed up-and-go to identify frail members of the older population.
AB  - BACKGROUND: Fried's definition of frailty is widely used but its measurement is
      problematic. Timed up-and-go (TUG) is a simple measure of mobility that may be a
      useful proxy for frailty. Here, we describe the distribution of frailty and TUG
      in the older population of Ireland and discuss the extent to which TUG identifies
      the frail and prefrail populations. METHODS: A total of 1,814 participants of The
      Irish Longitudinal Study on Ageing aged 65 and older completed a comprehensive
      health assessment. Frailty was defined by having three or more of low gait speed,
      low grip strength, unintentional weight loss, self-reported exhaustion, and low
      physical activity. ROC curves were used to identify how well TUG discriminates
      the frail and prefrail populations and whether TUG improves on gait speed as a
      single objective measure of frailty. RESULTS: Among the Irish population aged 65
      and older, 7.7% were frail and 44.0% were prefrail. TUG identifies frail members
      of the population well (AUC = 0.87) but is less able to discriminate the nonfrail
      from the prefrail or frail populations (AUC = 0.73). TUG captures the components
      of frailty that become more common with age but does not discriminate the
      components that do not, for example, unintended weight loss or exhaustion. There
      is no advantage in using TUG instead of gait speed with respect to identifying
      frailty. CONCLUSIONS: TUG is a sensitive and specific measure of frailty that
      offers advantages in its measurement where the full application or interpretation
      of Fried's criteria is impracticable; however, TUG cannot be used to reliably
      identify prefrail individuals.

PMID- 22987797
TI  - Motoric cognitive risk syndrome and the risk of dementia.
AB  - BACKGROUND: Despite growing evidence of links between gait and cognition in
      aging, cognitive risk assessments that incorporate motoric signs have not been
      examined. We sought to validate a new Motoric Cognitive Risk (MCR) syndrome to
      identify individuals at high risk of developing dementia. METHODS: We evaluated
      997 community residing individuals aged 70 and older participating in the
      Einstein Aging Study over a median follow-up time of 36.9 months. MCR syndrome
      was defined as presence of cognitive complaints and slow gait (one standard
      deviation below age- and sex-specific gait speed means) in nondemented
      individuals. Cox models were used to evaluate the effect of MCR syndrome on the
      risk of developing dementia and subtypes. RESULTS: Fifty-two participants met
      criteria for MCR syndrome at baseline with a prevalence of 7% (95% CI: 5-9%).
      Prevalence of MCR increased with age. Participants with MCR were at higher risk
      of developing dementia (hazard ratio [HR] adjusted for age, sex, and education:
      3.27, 95% CI: 1.55-6.90) and vascular dementia (adjusted HR: 12.81, 95% CI: 4.98
      32.97). The association of MCR with risk of dementia or vascular dementia
      remained significant even after accounting for other confounders and diagnostic
      overlap with "cognitive" mild cognitive impairment syndrome subtypes.
      CONCLUSIONS: A motor-based MCR syndrome provides a clinical approach to identify
      individuals at high risk for dementia, especially vascular dementia, to target
      for further investigations and who may benefit from preventive interventions.

PMID- 22987799
TI  - Enantioselective aza-Morita-Baylis-Hillman reactions of acrylonitrile catalyzed
      by palladium(II) pincer complexes having C2-symmetric chiral bis(imidazoline)
      ligands.

PMID- 22987798
TI  - Genetic labeling of steroidogenic factor-1 (SF-1) neurons in mice reveals
      ventromedial nucleus of the hypothalamus (VMH) circuitry beginning at
      neurogenesis and development of a separate non-SF-1 neuronal cluster in the
      ventrolateral VMH.
AB  - The ventromedial nucleus of the hypothalamus (VMH) influences a wide variety of
      physiological responses. Here, using two distinct but complementary genetic
      tracing approaches in mice, we describe the development of VMH efferent
      projections, as marked by steroidogenic factor-1 (SF-1; NR5A1). SF-1 neurons were
      visualized by Tau-green fluorescent protein (GFP) expressed from the endogenous
      Sf-1 locus (Sf-1(TauGFP)) or by crossing the transgenic Sf1:Cre driver to a GFP
      reporter strain (Z/EG(Sf1:Cre)). Strikingly, VMH projections were visible early,
      at embryonic (E) 10.5, when few postmitotic SF1 neurons have been born,
      suggesting that formation of VMH circuitry begins at the onset of neurogenesis.
      At E14.5, comparison of these two reporter lines revealed that SF1-positive
      neurons in the ventrolateral VMH (VMH(vl)) persist in Z/EG(Sf1:Cre) embryos but
      are virtually absent in Sf-1(TauGFP). Therefore, although the entire VMH
      including the VMH(vl) shares a common lineage, the VMH(vl) further differentiates
      into a neuronal cluster devoid of SF-1. At birth, extensive VMH projections to
      broad regions of the brain were observed in both mouse reporter lines, matching
      well with those previously discovered by injection of axonal anterograde tracers
      in adult rats. In summary, our genetic tracing studies show that VMH efferent
      projections are highly conserved in rodents and are established far earlier than
      previously appreciated. Moreover, our results imply that neurons in the VMH(vl)
      adopt a distinct fate early in development, which might underlie the unique
      physiological functions associated with this VMH subregion.

PMID- 22987800
TI  - Autoreactive T cells bypass negative selection and respond to self-antigen
      stimulation during infection.
AB  - Central and peripheral tolerance prevent autoimmunity by deleting the most
      aggressive CD8(+) T cells but they spare cells that react weakly to tissue
      restricted antigen (TRA). To reveal the functional characteristics of these
      spared cells, we generated a transgenic mouse expressing the TCR of a TRA
      specific T cell that had escaped negative selection. Interestingly, the isolated
      TCR matches the affinity/avidity threshold for negatively selecting T cells, and
      when developing transgenic cells are exposed to their TRA in the thymus, only a
      fraction of them are eliminated but significant numbers enter the periphery. In
      contrast to high avidity cells, low avidity T cells persist in the antigen
      positive periphery with no signs of anergy, unresponsiveness, or prior
      activation. Upon activation during an infection they cause autoimmunity and form
      memory cells. Unexpectedly, peptide ligands that are weaker in stimulating the
      transgenic T cells than the thymic threshold ligand also induce profound
      activation in the periphery. Thus, the peripheral T cell activation threshold
      during an infection is below that of negative selection for TRA. These results
      demonstrate the existence of a level of self-reactivity to TRA to which the
      thymus confers no protection and illustrate that organ damage can occur without
      genetic predisposition to autoimmunity.

PMID- 22987801
TI  - LAPCs promote follicular helper T cell differentiation of Ag-primed CD4+ T cells
      during respiratory virus infection.
AB  - The humoral immune response to most respiratory virus infections plays a
      prominent role in virus clearance and is essential for resistance to reinfection.
      T follicular helper (Tfh) cells are believed to support the development both of a
      potent primary antibody response and of the germinal center response critical for
      memory B cell development. Using a model of primary murine influenza A virus
      (IAV) infection, we demonstrate that a novel late activator antigen-presenting
      cell (LAPC) promotes the Tfh response in the draining lymph nodes (dLNs) of the
      IAV-infected lungs. LAPCs migrate from the infected lungs to the dLN "late,"
      i.e., 6 d after infection, which is concomitant with Tfh differentiation. LAPC
      migration is CXCR3-dependent, and LAPC triggering of Tfh cell development
      requires ICOS-ICOSL-dependent signaling. LAPCs appear to play a pivotal role in
      driving Tfh differentiation of Ag-primed CD4(+) T cells and antiviral antibody
      responses.

PMID- 22987802
TI  - Macrophages induce differentiation of plasma cells through CXCL10/IP-10.
AB  - In tonsils, CD138(+) plasma cells (PCs) are surrounded by CD163(+) resident
      macrophages (Ms). We show here that human Ms (isolated from tonsils or generated
      from monocytes in vitro) drive activated B cells to differentiate into
      CD138(+)CD38(++) PCs through secreted CXCL10/IP-10 and VCAM-1 contact. IP-10
      production by Ms is induced by B cell-derived IL-6 and depends on STAT3
      phosphorylation. Furthermore, IP-10 amplifies the production of IL-6 by B cells,
      which sustains the STAT3 signals that lead to PC differentiation. IP-10-deficient
      mice challenged with NP-Ficoll show a decreased frequency of NP-specific PCs and
      lower titers of antibodies. Thus, our results reveal a novel dialog between Ms
      and B cells, in which IP-10 acts as a PC differentiation factor.

PMID- 22987803
TI  - Bcl6 expression specifies the T follicular helper cell program in vivo.
AB  - T follicular helper cells (Tfh cells) play a pivotal role in germinal center
      reactions, which require B cell lymphoma 6 (Bcl6) transcription factor. To
      analyze their relationships with other effector T cell lineages and their
      stability in vivo, we developed and analyzed a new Bcl6 reporter mouse alone or
      together with other lineage reporter systems. Assisted with genome-wide
      transcriptome analysis, we show substantial plasticity of T cell differentiation
      in the early phase of immune response. At this stage, CXCR5 appears to be
      expressed in a Bcl6-independent manner. Once Bcl6 is highly expressed, Tfh cells
      can persist in vivo and some of them develop into memory cells. Together, our
      results indicate Bcl6 as a bona fide marker for Tfh polarized program.

PMID- 22987805
TI  - Combining MR elastography and diffusion tensor imaging for the assessment of
      anisotropic mechanical properties: a phantom study.
AB  - PURPOSE: To investigate the anisotropic elasticity of soft tissues using MR
      elastography (MRE) combined with diffusion tensor imaging (DTI). MATERIALS AND
      METHODS: The storage moduli parallel (MU(||)) and perpendicular (MU(?)) to the
      local fiber orientation were calculated assuming a transversely isotropic model.
      The local fiber orientation was provided by DTI. The proposed technique was
      validated against rheometry using anisotropic viscoelastic phantoms with various
      fiber volume fractions (V(f) = 0%, 15%, and 35%) and bovine skeletal muscle
      samples. RESULTS: The anisotropic ratio (MU(||)/MU(?)) as measured by MRE
      correlated well with rheometry for all samples (R(2) = 0.809). The combined
      MRE/DTI technique was also able to differentiate different levels of mechanical
      anisotropy with the mechanical anisotropy (MU(||)/MU(?)) of the V(f) = 35%
      phantoms being significantly higher than the V(f) = 15% and the isotropic (V(f) =
      0%) phantoms. The bovine muscle samples showed significantly higher mechanical
      anisotropy than all phantoms. CONCLUSION: This study has demonstrated the
      feasibility of the proposed imaging technique for characterizing mechanical
      anisotropy of anisotropic materials and biological tissues, and validated the
      mechanical anisotropy results.

PMID- 22987804
TI  - Temporal changes in N-acylethanolamine content and metabolism throughout the peri
      adolescent period.
AB  - Fatty acid amide hydrolase (FAAH) regulates tissue concentrations of N
      acylethanolamines (NAEs), including the endocannabinoid, N
      arachidonylethanolamide (anandamide, AEA). FAAH activity and NAEs are widely
      distributed throughout the brain and FAAH activity regulates an array of
      processes including emotion, cognition, inflammation, and feeding. However, there
      is relatively little research describing how this system develops throughout
      adolescence, particularly within limbic circuits regulating stress and reward
      processing. Thus, this study characterized temporal changes in NAE content (AEA,
      oleoylethanolamine [OEA], and palmitoylethanolamide [PEA]) and FAAH activity
      across the peri-adolescent period, in four corticolimbic structures (amygdala,
      hippocampus, prefrontal cortex, and hypothalamus). Brain tissue of male Sprague
      Dawley rats was collected on postnatal days (PND) 25, 35, 45, and 70,
      representing pre-adolescence, early- to mid-adolescence, late adolescence, and
      adulthood, respectively. Tissue was analyzed for AEA, OEA, and PEA content as
      well as FAAH activity at each time point. AEA, OEA, and PEA exhibited a similar
      temporal pattern in all four brain regions. NAE concentrations were lowest at PND
      25 and highest at PND 35. NAE concentrations decreased between PNDs 35 and 45 and
      increased between PNDs 45 and 70. FAAH activity mirrored the pattern of NAE
      content in which it decreased between PNDs 25 and 35, increased between PNDs 35
      and 45, and decreased between PNDs 45 and 70. These age-dependent patterns of NAE
      content and FAAH activity demonstrate temporal specificity to the development of
      this system and could contribute to alterations in stress sensitivity,
      emotionality, and executive function which also fluctuate during this
      developmental period.

PMID- 22987806
TI  - Fluorescence spectroscopic investigation of competitive interactions between
      ochratoxin A and 13 drug molecules for binding to human serum albumin.
AB  - Ochratoxin A (OTA) is a highly toxic mycotoxin found worldwide in cereals, foods,
      animal feeds and different drinks. Based on previous studies, OTA is one of the
      major causes of the chronic tubulointerstitial nephropathy known as Balkan
      endemic nephropathy (BEN) and exerts several other adverse effects shown by cell
      and/or animal models. It is a well-known fact that OTA binds to various albumins
      with very high affinity. Recently, a few studies suggested that reducing the
      bound fraction of OTA might reduce its toxicity. Hypothetically, certain drugs
      can be effective competitors displacing OTA from its albumin complex. Therefore,
      we examined 13 different drug molecules to determine their competing abilities to
      displace OTA from human serum albumin (HSA). Competitors and ineffective
      chemicals were identified with a steady-state fluorescence polarization-based
      method. After characterization the competitive abilities of individual drugs,
      drug pairs were formed and their displacing activity were tested in OTA-HSA
      system. Indometacin, phenylbutazone, warfarin and furosemide showed the highest
      competing capacity but ibuprofen, glipizide and simvastatin represented
      detectable interaction too. Investigations of drug pairs raised the possibility
      of the presence of diverse binding sites of competing drugs. Apart from the
      chemical information obtained in our model, this explorative research might
      initiate future designs for epidemiologic studies to gain further in vivo
      evidence of long-term (potentially protective) effects of competing drugs
      administered to human patients.

PMID- 22987807
TI  - Marked variability in the radiographic features of cartilage-hair hypoplasia:
      case report and review of the literature.
AB  - Cartilage-hair hypoplasia (CHH) is a rare recessive metaphyseal chondrodysplasia
      characterized by severe short stature, ectodermal dysplasia, anemia in childhood,
      immune deficiency, susceptibility to malignancy, and normal intelligence. Short,
      thick long bones, metaphyseal flaring and irregularities, and globular epiphyses
      at the knees and ankles are the typical radiographic findings. The diagnosis is
      primarily made on the basis of clinical features, although mutations in the RMRP
      gene have recently been described in affected individuals, facilitating
      confirmation of the clinical diagnosis in atypical patients. We present a patient
      with two RMRP mutations whose stature and ectodermal features supported the
      diagnosis of CHH, but whose radiographic findings and other extraskeletal
      findings did not. We propose that the most consistent and reliable features of
      CHH are short stature of prenatal onset and ectodermal dysplasia, and suggest
      that the diagnosis of CHH be considered and mutation analysis pursued even when
      typical radiographic findings are absent.

PMID- 22987810
TI  - Photoswitchable upconversion luminescence of rare-earth nanophosphors with
      covalently grafted spiropyran.

PMID- 22987808
TI  - Orthotopic VX rabbit tongue cancer model with FDG-PET and histologic
      characterization.
AB  - BACKGROUND: We present our experience with the use of an immunocompetent medium
      sized animal model of tongue cancer that may be suitable for imaging and surgical
      studies. METHODS: A New Zealand white rabbit model of tongue cancer was created
      by injecting a VX tumor cell suspension grown in culture into the tongue of our
      model. The tumor was examined 7 days following implantation by physical
      examination, photography, and (18) fluoro 2-deoxyglucose-positron emission
      tomography (FDG-PET). At 12 days postimplantation, the model was again studied as
      described above prior to euthanization, and then tongue excision and bilateral
      neck dissections were performed. All tissue was examined by histology. RESULTS:
      We confirmed a successful orthotopic tongue cancer model that resulted in
      cervical nodal metastases. CONCLUSION: This model may be a useful model of
      orthotopic head and neck cancer for future surgical or imaging research.

PMID- 22987811
TI  - Nonlocal regularization for active appearance model: Application to medial
      temporal lobe segmentation.
AB  - The human medial temporal lobe (MTL) is an important part of the limbic system,
      and its substructures play key roles in learning, memory, and neurodegeneration.
      The MTL includes the hippocampus (HC), amygdala (AG), parahippocampal cortex
      (PHC), entorhinal cortex, and perirhinal cortex--structures that are complex in
      shape and have low between-structure intensity contrast, making them difficult to
      segment manually in magnetic resonance images. This article presents a new
      segmentation method that combines active appearance modeling and patch-based
      local refinement to automatically segment specific substructures of the MTL
      including HC, AG, PHC, and entorhinal/perirhinal cortex from MRI data. Appearance
      modeling, relying on eigen-decomposition to analyze statistical variations in
      image intensity and shape information in study population, is used to capture
      global shape characteristics of each structure of interest with a generative
      model. Patch-based local refinement, using nonlocal means to compare the image
      local intensity properties, is applied to locally refine the segmentation results
      along the structure borders to improve structure delimitation. In this manner,
      nonlocal regularization and global shape constraints could allow more accurate
      segmentations of structures. Validation experiments against manually defined
      labels demonstrate that this new segmentation method is computationally
      efficient, robust, and accurate. In a leave-one-out validation on 54 normal young
      adults, the method yielded a mean Dice kappa of 0.87 for the HC, 0.81 for the AG,
      0.73 for the anterior parts of the parahippocampal gyrus (entorhinal and
      perirhinal cortex), and 0.73 for the posterior parahippocampal gyrus.

PMID- 22987812
TI  - Health characteristics of inland waterway merchant marine captains and pilots.
AB  - BACKGROUND: Most published studies on seafarer health have focused on patterns of
      mortality, injury and communicable diseases. Little information is available
      regarding lifestyle-related cardio-metabolic disease in maritime populations.
      AIMS: To describe health characteristics of a population of US inland waterway
      merchant marine captains and pilots. METHODS: A cross-sectional study of the
      health characteristics of mariners required to complete the United States Coast
      Guard physical assessment at a regional medical centre from 2003-10. Variables
      collected included self-reported smoking status, body mass index, fasting lipids,
      glucose and triglyceride levels, blood pressure and treadmill time and maximal
      oxygen uptake as measured using the Bruce Protocol. Major medical conditions
      related to lifestyle and risk for metabolic syndrome were also assessed. RESULTS:
      There were 388 participants. The study population had high prevalence of obesity
      (61%), smoking (41%), high triglycerides (42%), low HDL cholesterol (47%), high
      blood pressure (42%), high fasting glucose (22%) and three or more features of
      the metabolic syndrome (39%). CONCLUSIONS: This population exhibited a high
      prevalence of chronic disease risk factors and could potentially benefit from
      health promotion programmes aimed at improving health and fitness.

PMID- 22987814
TI  - Effects of irradiation on osteoblast-like cells on different titanium surfaces in
      vitro.
AB  - The aim of this study was to investigate the effects of irradiation on adhesion
      ability, proliferation, and differentiation of MC3T3-E1 cells on microarc
      oxidation (MAO) titanium surfaces and polished titanium (PT) surfaces. MC3T3-E1
      cells were exposed to a single dose at 2, 4, 6, 8, or 10 Gy using a (60) Co
      source, with tissue culture polystyrene plates chosen as controls. On all
      surfaces, irradiation resulted in a dose-dependent decrease in cellular
      proliferation. At 4 Gy dose, the cell proliferation of cells decreased by 17.8%
      on MAO and 18.6% on PT surfaces, respectively, compared with nonirradiated
      controls. Cells exposed to 8 Gy dose showed significant inhibition in collagen
      secretion and osteogenesis-related genes expression (OSX, COL-Ialpha1, and OCN).
      In contrast, irradiation increased cell adhesion to three surfaces dose
      dependently. It was also demonstrated that cells on MAO surface showed higher
      adhesion and collagen secretion than on PT surface at different radiation doses.
      This study revealed the effects of irradiation on osteoblasts in vitro on two
      titanium surfaces. MAO surface could be used in dental implants in irradiated
      bone due to enhanced adhesion ability and collagen secretion in osteoblasts.

PMID- 22987815
TI  - Reactions of metal-metal quintuple bonds with alkynes: [2+2+2] and [2+2]
      cycloadditions.

PMID- 22987813
TI  - Afferent regulation of chicken auditory brainstem neurons: rapid changes in
      phosphorylation of elongation factor 2.
AB  - The relationships between protein synthesis and neuronal survival are poorly
      understood. In chicken nucleus magnocellularis (NM), significant alterations in
      overall protein synthesis precede neuronal death induced by deprivation of
      excitatory afferent activity. Previously we demonstrated an initial reduction in
      the overall rate of protein synthesis in all deprived NM neurons, followed by
      quick recovery (starting at 6 hours) in some, but not all, neurons. Neurons with
      recovered protein synthesis ultimately survive, whereas others become "ghost"
      cells (no detectable Nissl substance) at 12-24 hours and die within 48 hours. To
      explore the mechanisms underlying this differential influence of afferent input
      on protein synthesis and cell survival, the current study investigates the
      involvement of eukaryotic translation elongation factor 2 (eEF2), the
      phosphorylation of which reduces overall protein synthesis. Using
      immunocytochemistry for either total or phosphorylated eEF2 (p-eEF2), we found
      significant reductions in the level of phosphorylated, but not total, eEF2 in NM
      neurons as early as 0.5-1 hour following cochlea removal. Unexpectedly, neurons
      with low levels of p-eEF2 show reduced protein synthesis at 6 hours, indicated by
      a marker for active ribosomes. At 12 hours, all "ghost" cells exhibited little or
      no p-eEF2 staining, although not every neuron with a comparable low level of p
      eEF2 was a "ghost" cell. These observations demonstrate that a reduced level of p
      eEF2 is not responsible for immediate responses (including reduced overall
      protein synthesis) of a neuron to compromised afferent input but may impair the
      neuron's ability to initiate recovery signaling for survival and make the neuron
      more vulnerable to death.

PMID- 22987816
TI  - New spectrofluorimetric and spectrophotometric methods for the determination of
      the analgesic drug, nalbuphine in pharmaceutical and biological fluids.
AB  - We describe the first studies of a simple and sensitive spectrofluorimetric and
      spectrophotometric methods for the analysis of nalbuphine (NLB) in dosage form
      and biological fluids. The spectrofluorimetric method was based on the oxidation
      of NLB with Ce(IV) to produce Ce(III) and its fluorescence was monitored at 352
      nm after excitation at 250 nm. The spectrophotometric method involves addition of
      a known excess of Ce(IV) to NLB in acid medium, followed by determination of
      residual Ce(IV) by reacting with a fixed amount of methyl orange and measuring
      absorbance at 510 nm. In both methods, the amount of Ce(IV) reacted corresponds
      to the amount of NLB and measured fluorescence or absorbance were found to
      increase linearly with the concentration of NLB, which are corroborated by
      correlation coefficients of 0.9997 and 0.9999 for spectrofluorimetric and
      spectrophotometric methods, respectively. Different variables affecting the
      reaction conditions such as concentrations of Ce(IV), type and concentration of
      acid medium, reaction time, temperature, and diluting solvents were carefully
      studied and optimized. The accuracy and precision of the methods were evaluated
      on intra-day and inter-day basis. The proposed methods were successfully applied
      for the determination of NLB in pharmaceutical formulation and biological samples
      with good recoveries.

PMID- 22987819
TI  - A highly efficient Friedel-Crafts reaction of tertiary alpha-hydroxyesters or
      alpha-hydroxyketones to alpha-quaternary esters or ketones.
AB  - A catalytic Friedel-Crafts arylation of alpha-hydroxyesters or alpha
      hydroxyketones with electron-rich aromatic compounds to furnish alpha-quaternary
      esters/ketones has been developed. The cheap and easy to handle catalyst HClO(4) 
      (70 %, aq) was identified as a powerful catalyst for this arylation reaction.

PMID- 22987817
TI  - Economic analysis of FDG-PET-guided management of the neck after primary
      chemoradiotherapy for node-positive head and neck squamous cell carcinoma.
AB  - BACKGROUND: The aim of this economic analysis was to model different strategies
      using pre-treatment nodal stage or nodal response assessment with CT or positron
      emission tomography (PET)/CT to determine the need for neck dissection. METHODS:
      A cost-minimization analysis was developed on the basis of probability data from
      a prospective study of PET-guided management of the neck in patients achieving a
      complete response at the primary site. Costs were derived from our institution's
      activity-based clinical costing system. The effect of uncertainty was tested with
      sensitivity and scenario analyses including nationally representative cost data.
      RESULTS: Strategies incorporating PET had a 7% rate for neck dissection compared
      with 44% for CT-guided and 90% for planned neck dissection. The cost per patient
      was A$16,502 for planned neck dissection, A$8014 for CT-guided, and A$2573 for
      PET-guided. A policy with PET used only for incomplete response on CT was the
      least-cost strategy (A$2111). Policies incorporating PET remained the most
      efficient for all sensitivity/scenario analyses. CONCLUSION: The incorporation of
      PET/CT into nodal response assessment significantly reduced the number of
      unnecessary neck dissections and generated considerable cost savings in our
      cohort.

PMID- 22987818
TI  - WDR35 mutation in siblings with Sensenbrenner syndrome: a ciliopathy with
      variable phenotype.
AB  - Sensenbrenner syndrome and unclassified short rib-polydactyly conditions are
      ciliopathies with overlapping phenotypes and genetic heterogeneity. Mutations in
      WDR35 were identified recently in a sub-group of patients with Sensenbrenner
      syndrome and in a single family that presented with an unclassified form of short
      rib polydactyly (SRP) syndrome. We report on siblings with an unusual combination
      of phenotypes: narrow thorax, short stature, minor anomalies, developmental
      delay, and severe hepatic fibrosis leading to liver failure and early death in
      two of the children. Both parents were unaffected suggesting autosomal recessive
      inheritance. The family and their affected children were followed over a decade.
      Exome sequencing was performed in one affected individual. It showed a homozygous
      missense mutation in a highly conserved position of the WDR35 gene. This family
      represents a WDR35-ciliopathy with a complex clinical presentation that includes
      significant overlap of the phenotypes described in Sensenbrenner syndrome and the
      unclassified SRPs. The accurate molecular diagnosis of this family exemplifies
      the power of exome sequencing in the diagnosis of Mendelian disorders and enabled
      us to broaden and refine our understanding of Sensenbrenner syndrome and SRP.
      Detailed genotype-phenotype information is provided as well as discussion of
      previously reported cases.

PMID- 22987820
TI  - Novel objective classification of reactive microglia following hypoglossal
      axotomy using hierarchical cluster analysis.
AB  - A total of 136 microglia were intracellularly labeled and their morphological
      features were evaluated by 3D morphometric measurement. According to hierarchical
      cluster analysis, microglia were objectively categorized into four groups termed
      types I-IV. The validity of this classification was confirmed by principal
      component analysis and linear discriminant analysis. Type I microglia were found
      in sham-operated mice and in mice sacrificed 28 days (D28) after axotomy. The
      appearance of type I cells was similar to so-called ramified microglia in a
      resting state. Type II microglia were mainly seen in D14 mice, which exhibited
      small cell bodies with thin and short processes. Interestingly, none of the
      already-known morphological types of microglia seemed to be comparable to type II
      cells. We thus named type II microglia "small ramified" cells. Types III and IV
      microglia were mainly seen in D3 and D7 mice and their appearances were similar
      to hypertrophied and bushy cells, respectively. Proliferating cell nuclear
      antigen (PCNA), a mitosis marker, was almost exclusively expressed in D3 mice. On
      the other hand, voltage-dependent potassium channels (Kv1.3/1.5), neurotoxicity
      related molecules, were most highly expressed in D14 mice. Increased expression
      of Kv1.3/1.5 in D14 mice was suppressed by minocycline treatment. These findings
      indicate that type II and III microglia may be involved in neurotoxicity and
      mitosis, respectively. Type IV microglial cells are assumed to be in the process
      of losing mitotic activity and gaining neurotoxicity. Our data also suggest that
      type II microglia can be a potential therapeutic target against neurodegenerative
      diseases.

PMID- 22987821
TI  - Bovine osteoblasts cultured on polyanionic collagen scaffolds: an ultrastructural
      and immunocytochemical study.
AB  - Collagen is the most abundant protein in the body and is also the most important
      component of the extracellular matrix. Collagen has several advantages as a
      biomaterial such as lack of toxicity, biocompatibility, biodegradability, and
      easy reabsorption. In this study, we examined bovine osteoblasts cultured on
      native or anionic collagen scaffolds prepared from bovine pericardium after
      selective hydrolysis of glutamine and asparagine side chain amides for periods
      from 24 (BP24) and 48 h (BP48). The cells were cultured in control and
      mineralization medium at 37  degrees C in the presence of 5% CO(2). Transmission
      and scanning electron microscopy, energy dispersive spectroscopy, and an
      immunocytochemical marker were used for analysis. Cells with an irregular
      morphology forming a confluent multilayer were observed on matrices kept in
      control medium. Most of these cells presented a polygonal or elongated flattened
      morphology. Several spherical deposits of calcium crystal associated with
      phosphorus were observed on the native and BP48 matrices. Similar results were
      observed in samples kept in control medium except with lower calcium/phosphorus
      ratio. Vesicles actively expelled from the cell membrane were also seen (do this
      vesicles corresponds to calcium/phosphorus deposits). Osteocalcin was clearly
      visible on matrices kept in mineralization medium and was more expression on the
      surface of BP48 matrices. The results showed that anionic collagen is able to
      support osteoblastic differentiation, regardless of the medium used. Finally, the
      BP48 matrix promoted better osteoblast differentiation than the native matrix.

PMID- 22987822
TI  - 12q14 microdeletion associated with HMGA2 gene disruption and growth restriction.
AB  - The 12q14 microdeletion syndrome is a rare condition that has previously been
      characterized by pre- and postnatal growth restriction, proportionate short
      stature, failure to thrive, developmental delay, and osteopoikilosis. Previously
      reported microdeletions within this region have ranged in size from 1.83 to 10.12
      Mb with a proposed 2.61 Mb smallest region of overlap containing the LEMD3,
      HMGA2, and GRIP1 genes. Here, we report on the identification of a 12q14
      microdeletion in a female child presenting with proportionate short stature,
      failure to thrive, and speech delay. The genomic loss (minimum size 4.17 Mb,
      maximum size 4.21 Mb) contained 25 RefSeq genes including IRAK3, GRIP1, and the
      3' portion of the HMGA2 gene. This is the first partial deletion of HMGA2
      associated with the 12q14 microdeletion syndrome. This case further clarifies the
      association of LEMD3 deletions with the 12q14 microdeletion syndrome and provides
      additional support for the role of the HMGA2 gene in human growth.

PMID- 22987823
TI  - Electroswitching of emission and coloration with quick response and high
      reversibility in an electrochemical cell.
AB  - No fade to grey: Electroswitching of emission and coloration was achieved for a
      combination of a luminescent Eu(III) complex and an electrochromic molecule of
      diheptyl viologen (HV(2+)), indicating that such a combination could be used as a
      display material with dual emissive and reflective modes. The Prussian blue (PB)
      modified electrode improved the response time and reversibility for the switching
      of emission and coloration, by acting as a counter electrode for the
      electrochromism of HV(2+).

PMID- 22987824
TI  - Inequality and inequity in access to health care and treatment for chronic
      conditions in China: the Guangzhou Biobank Cohort Study.
AB  - Non-communicable diseases (NCDs) are a large and rapidly-growing problem in China
      and other middle-income countries. Clinical treatment of NCDs is long-term and
      expensive, so it may present particular problems for equality and horizontal
      equity (equal treatment for equal need) in access to health care, although little
      is known about this at present in low- and middle-income countries. To address
      this gap, and inform policy for a substantial proportion of the global
      population, we examined inequality and inequity in general health care
      utilization (doctor consultations and hospital admissions) and in treatment of
      chronic conditions (hypertension, hyperglycaemia and dyslipidaemia), in 30 499
      Chinese adults aged >=50 years from one of China's richest provinces, using the
      Guangzhou Biobank Cohort Study (2003-2008). We used concentration indices to test
      for inequality and inequity in utilization by household income per head.
      Inequality was decomposed to show the contributions of income, indicators of
      'need for health care' (age, sex, self-rated health, coronary heart disease risk
      and chronic obstructive pulmonary disease) and non-need factors (education,
      occupation, out-of-pocket health care payments and health insurance). We found
      inequality and inequity in treatment of chronic conditions but not in general
      health care utilization. Using more objective and specific measures of 'need for
      health care' increased estimates of inequity for treatment of chronic conditions.
      Income and non-need factors (especially health insurance, education and
      occupation) made the largest contributions to inequality. Further work is needed
      on why access to treatment for chronic conditions in China is restricted for
      those on low incomes and how these inequities can be mitigated. 

PMID- 22987825
TI  - Addressing the challenges of improving primary care quality in Uzbekistan: a
      qualitative study of chronic heart failure management.
AB  - Uzbekistan has a well-developed primary care system, with universal access to
      care, but faces challenges in improving the quality of clinical care provided.
      This study aimed to identify barriers to quality improvement by focusing on one
      common condition, Chronic Heart Failure (CHF), for which there are evidence-based
      international guidelines for management. To identify the challenges to improving
      the quality of care for CHF in line with such guidelines we took a qualitative
      approach, interviewing 15 physicians and 30 patients in detail about their
      experiences of CHF management. Despite recent improvements to the training of
      primary care physicians, their access to up-to-date information was limited, and
      they were disproportionately reliant on information from pharmaceutical
      companies. The main barriers to implementing international standards of care
      were: reluctance of physicians (and patients) to abandon ineffective
      interventions; enduring, system-wide incentives for clinically unnecessary
      hospitalization; and the lack of structural support for evidence-based health
      services improvement. Patients were in general positive about adherence to
      medications, but faced some problems in affording drugs and hospital care. Future
      interventions to strengthen primary care should be implemented with evaluations
      of their impact on the processes and outcomes of care for chronic conditions. 

PMID- 22987831
TI  - Multiphoton imaging of freezing and heating effects in plant leaves.
AB  - Thermally-induced changes in Arabidopsis thaliana leaves were investigated with a
      novel cryo microscope by multiphoton, fluorescence lifetime and spectral imaging
      as well as micro spectroscopy. Samples were excited with fs pulses in the near
      infrared range and cooled/heated in a cryogenic chamber. The results show
      morphological changes in the chloroplast distribution as well as a shift from
      chlorophyll to cell-wall fluorescence with decreasing temperature. At
      temperatures below -40  degrees C, also second harmonic generation was observed.
      The measurements illustrate the suitability of multiphoton imaging to investigate
      thermally-induced changes at temperatures used for cryopreservation as well as
      for basic investigations of thermal effects on plant tissue in general.

PMID- 22987832
TI  - Performance of different screening methods for the determination of urinary
      glycosaminoclycans.
AB  - BACKGROUND: The study aim was to compare the performance of three different
      methods used for determining urinary glycosaminoglycans (GAG) levels in spot and
      24-h urine samples. METHODS: Performance characteristics were studied for
      cetylpyridinium chloride (CPC), and manual and automated dimethylmethylene blue
      (DMB) methods. RESULTS: For automated DMB method, within-run precisions were
      9.10% and 1.98%, and between-day precisions were 13.0% and 5.81% in low- and high
      urine pools, respectively. The method was linear up to 100 mg/L of GAG
      concentration. The detection limit of the method was 0.71 mg/L. Mean recovery was
      95.7%. CONCLUSIONS: The automated DMB method was found to give better performance
      characteristics than cetylpyridinium chloride (CPC) and manual DMB methods. It is
      a fast, cheap, simple and reliable method and can be applied in many diseases in
      which GAG is used as a screening test.

PMID- 22987833
TI  - Point-of-care testing on admission to the intensive care unit: lactate and
      glucose independently predict mortality.
AB  - BACKGROUND: The aim of the study was to retrospectively investigate whether
      parameters of routine point-of-care testing (POCT) predict hospital mortality in
      critically ill surgical patients on admission to the intensive care unit (ICU).
      METHODS: Arterial blood analyses of 1551 patients on admission to the adult
      surgical ICU of the Technical University Munich were reviewed. POCT was performed
      on a blood gas analyser. The association between acid-base status and mortality
      was evaluated. Metabolic acidosis was defined by base excess (BE) <-2 mmol/L and,
      wherever applicable, subdivided into lactic acidosis by lactate >50% of BE, anion
      gap (AG)-acidosis by AG >16 mmol/L, hyperchloraemic acidosis by chloride >115
      mmol/L. Metabolic alkalosis was defined by BE >=3 mmol/L. Logistic regression
      analysis identified variables independently associated with mortality. RESULTS:
      Overall mortality was 8.8%. Mortality was greater in male patients (p=0.012).
      Mean age was greater in non-survivors (p<0.0005). Nine hundred and eighty-six
      patients showed no metabolic acid-base disorder (mortality 7.3%), thereof 26
      patients with pCO(2)>55 mm Hg (mortality 23.1%). Three hundred and seventy-seven
      patients presented with acidosis (mortality 11.4%), thereof 163 patients with
      lactic acidosis (mortality 19%). Mortality for alkalosis (174 patients) was
      12.1%. Mean blood glucose level for non-survivors was higher compared to
      survivors (p<0.0005). Logistic regression analysis identified lactate, glucose,
      age, male gender as independent predictors of mortality. CONCLUSIONS: Lactate and
      glucose on ICU admission independently predict mortality. BE and AG failed as
      prognostic markers. Lactic acidosis showed a high mortality rate implying that
      lactate levels should be obtained on ICU admission. Prevalence of hyperchloraemic
      acidosis was low. Metabolic alkalosis was associated with an increased mortality.
      Further studies on this disturbance and its attendant high mortality are
      warranted.

PMID- 22987834
TI  - Shop for quality or quantity? Volumes and costs in clinical laboratories.
AB  - BACKGROUND: The increasing need to reduce the costs of providing diagnostic
      laboratory services has prompted initiatives based on the centralization and
      consolidation of laboratory facilities. However, the majority of papers and
      experiences reported in literature focus on "cost per test" thus overlooking the
      real value of a laboratory service, which requires more complex economic
      evaluations, such as cost-benefit, cost-effectiveness, and cost-utility analysis.
      It is important to perform cost analysis, which is no mean feat, by taking into
      consideration all variables affecting the final and true cost per test. METHODS:
      The present study was conducted in order to evaluate the costs of delivering
      laboratory services in 20 Italian clinical laboratories using a widely accepted
      methodology, the so-called "activity-based costing analysis". RESULTS: The
      finding of a trend towards a decrease in total costs - due to an increase in test
      volumes - attained statistical significance only for quantities of up to about
      1,100,00 tests per year. For 1,800,00 tests and more, the cost per test appeared
      to range from 1.5 to 2.0 ? irrespective of the different volumes. Regarding the
      relationship between volumes and number of staff, there is an evident linear
      relationship between the number of senior staff and volumes, whereas this trend
      is not observed in the case of medical technologists, the degree and type of
      automation strongly affecting this variable. CONCLUSIONS: The findings made in
      the present study confirm that the relationship between volumes and costs is not
      linear; since it is complex, numerous variables should be taken into account.

PMID- 22987835
TI  - Laboratory medicine and medical oncology: the tale of two Cinderellas.
AB  - Cancer represents a leading cause of death in the developed countries. The past
      50 years have witnessed major progress in both laboratory medicine and clinical
      oncology that has translated into improved prognosis of cancer patients. From the
      humble beginnings as unrelated specialties, major advances in the understanding
      of molecular bases of cancer progression led to increased interactions between
      laboratory medicine and clinical (mostly medical) oncology. Laboratory medicine
      is now an integral part of the management of cancer patients. The many aspects of
      the role of laboratory medicine in clinical oncology include the determination of
      biomarkers that are used in establishing the diagnosis, predicting response to
      therapy or prognosis, study of the host response to tumor growth, detection of
      treatment toxicity and determining the concentrations of anticancer drugs.

PMID- 22987836
TI  - Improving attitudes and knowledge toward organ donation among nursing students.
AB  - This study explored how an educational intervention related to organ donation
      affected the knowledge and attitude of a randomized two group sample of
      baccalaureate nursing students. A convenience sample of 101 subjects in the
      experimental group and 83 subjects in the control group were asked to complete a
      pretest. One week later the experimental group attended a one hour education
      intervention. Two weeks after intervention the pretest questionnaire was
      administered as a post test to the experimental and control groups. The
      introduction of specific education strategies improved the attitudes and
      knowledge base of the experimental group. SPSS results indicated a 40% increase
      in knowledge and an 8.5% increase in attitudes in the experimental group. Post
      intervention knowledge was the sole significant predictor of post-intervention
      attitude scores. Results support nurse educator's use of a short term educational
      intervention as a means to improve knowledge and attitudes towards donation among
      nursing students.

PMID- 22987837
TI  - Proteome changes in tomato lines transformed with phytoene synthase-1 in the
      sense and antisense orientations.
AB  - The commercial cultivation of genetically engineered (GE) crops in Europe has met
      with considerable consumer resistance, which has led to vigorous safety
      assessments including the measurement of substantial equivalence between the GE
      and parent lines. This necessitates the identification and quantification of
      significant changes to the metabolome and proteome in the GE crop. In this study,
      the quantitative proteomic analysis of tomato fruit from lines that have been
      transformed with the carotenogenic gene phytoene synthase-1 (Psy-1), in the sense
      and antisense orientations, in comparison with a non-transformed, parental line
      is described. Multidimensional protein identification technology (MudPIT), with
      tandem mass spectrometry, has been used to identify proteins, while
      quantification has been carried out with isobaric tags for relative and absolute
      quantification (iTRAQ). Fruit from the GE plants showed significant alterations
      to their proteomes compared with the parental line, especially those from the Psy
      1 sense transformants. These results demonstrate that MudPIT and iTRAQ are
      suitable techniques for the verification of substantial equivalence of the
      proteome in GE crops.

PMID- 22987838
TI  - Co-evolution between Grapevine rupestris stem pitting-associated virus and Vitis
      vinifera L. leads to decreased defence responses and increased transcription of
      genes related to photosynthesis.
AB  - Grapevine rupestris stem pitting-associated virus (GRSPaV) is a widespread virus
      infecting Vitis spp. Although it has established a compatible viral interaction
      in Vitis vinifera without the development of phenotypic alterations, it can occur
      as distinct variants that show different symptoms in diverse Vitis species. The
      changes induced by GRSPaV in V. vinifera cv 'Bosco', an Italian white grape
      variety, were investigated by combining agronomic, physiological, and molecular
      approaches, in order to provide comprehensive information about the global
      effects of GRSPaV. In two years, this virus caused a moderate decrease in
      physiological efficiency, yield performance, and sugar content in berries
      associated with several transcriptomic alterations. Transcript profiles were
      analysed by a microarray technique in petiole, leaf, and berry samples collected
      at veraison and by real-time RT-PCR in a time course carried out at five
      grapevine developmental stages. Global gene expression analyses showed that
      transcriptomic changes were highly variable among the different organs and the
      different phenological phases. GRSPaV triggers some unique responses in the
      grapevine at veraison, never reported before for other plant-virus interactions.
      These responses include an increase in transcripts involved in photosynthesis and
      CO(2) fixation, a moderate reduction in the photosynthesis rate and some defence
      mechanisms, and an overlap with responses to water and salinity stresses. It is
      hypothesized that the long co-existence of grapevine and GRSPaV has resulted in
      the evolution of a form of mutual adaptation between the virus and its host. This
      study contributes to elucidating alternative mechanisms used by infected plants
      to contend with viruses.

PMID- 22987839
TI  - Ecophysiology of nickel phytoaccumulation: a simplified biophysical approach.
AB  - Solute active transport or exclusion by plants can be identified by the values of
      the Transpiration Stream Concentration Factor (TSCF=xylem:solution solute
      concentration ratio). The aim of this study was to estimate this parameter for Ni
      uptake by the Ni-hyperaccumulator Leptoplax emarginata or the Ni-excluder
      Triticum aestivum cultivar 'Fidel'. The Intact Plant TSCF for nickel (IPTSCF(Ni))
      was calculated as the ratio between the nickel mass accumulation in the leaves
      and the nickel concentration in solution per volume of water transpired.
      Predominantly, Ni active transport occurred for L. emarginata, with IPTSCF(Ni)
      values of 4.7-7.2 and convective component proportions of the root Ni uptake flow
      of only 15-20% for a range of Ni concentrations in solutions of 2-16 umol Ni l(
      1), regardless of the growth period and the time of Ni uptake. Hyperaccumulator
      roots were permeable to both water and nickel (mean reflection coefficient for
      Ni, sigma(Ni), of 0.06), which was mainly attributed to an absence of exodermis.
      Results provide a new view of the mechanisms of Ni hyperaccumulation. By
      contrast, the wheat excluder was characterized by an extremely low mean
      IPTSCF(Ni) value of 0.006, characterizing a predominantly Ni sequestration in
      roots. From a methodological viewpoint, the 'microscopic' TSCF(Ni), measured
      directly on excised plants was 2.4 times larger than its recommended
      'macroscopic' IPTSCF(Ni) counterpart. Overall, IPTSCF and sigma determined on
      intact transpiring plants appeared to be very useful biophysical parameters in
      the study of the mechanisms involved in metal uptake and accumulation by plants,
      and in their modelling.

PMID- 22987840
TI  - The molecular architecture of the plant nuclear pore complex.
AB  - The nucleus contains the cell's genetic material, which directs cellular activity
      via gene regulation. The physical barrier of the nuclear envelope needs to be
      permeable to a variety of macromolecules and signals. The most prominent gateways
      for the transport of macromolecules are the nuclear pore complexes (NPCs). The
      NPC is the largest multiprotein complex in the cell, and is composed of multiple
      copies of ~30 different proteins called nucleoporins. Although much progress has
      been made in dissecting the NPC structure in vertebrates and yeast, the molecular
      architecture and physiological function of nucleoporins in plants remain poorly
      understood. In this review, we summarize the current knowledge regarding the
      plant NPC proteome and address structural and functional aspects of plant
      nucleoporins, which support the fundamental cellular machinery.

PMID- 22987841
TI  - Respiratory-induced vasoconstriction measured by light transmission and by laser
      Doppler signal.
AB  - Changes in finger tissue blood volume (TBV) measured by light transmission and in
      laser Doppler flow (LDF) were obtained during long breathing (of 12 s period) and
      associated with the respiratory phases, inspiration and expiration. For fifteen
      out of sixteen subjects TBV and LDF started to decrease 0-2 s after the start of
      expiration and increased during inspiration but the start of increase occurred
      before the start of inspiration, showing that the respiratory-induced changes in
      TBV and LDF are mainly associated with the expiration. Decrease of TBV and LDF
      after expiration was also found during the inspiratory gasps

PMID- 22987842
TI  - Australian health promotion practitioners' perceptions on evaluation of
      empowerment and participation.
AB  - Although participation and empowerment are hallmarks of the WHO vision of health
      promotion, it is acknowledged that they are difficult to evaluate. Devising
      adequate study designs, indicators and methods for the assessment of
      participation and empowerment should consider the experiences, concerns and
      constraints of health promotion practitioners. The aim of this study was to
      investigate health promotion practitioners' perspectives on general and
      methodological aspects of evaluation of empowerment and participation. Semi
      structured interviews were conducted with 17 experienced practitioners in
      community-based health promotion in New South Wales, Australia. The interviews
      covered benefits of and barriers to the evaluation of participation and
      empowerment, key indicators and methodological aspects. Interview transcripts
      were examined using thematic content analysis. The idea of evaluating empowerment
      and participation is supported by health promotion practitioners. Including
      indicators of empowerment and participation in the evaluation could also
      emphasise-to practitioners and citizens alike-the value of involving and enabling
      community members. The interviews highlighted the importance of a receptive
      environment for evaluation of empowerment and participation to take root. The
      resistance of health authorities towards empowerment indicators was seen as a
      challenge for funding evaluations. Community members should be included in the
      evaluation process, although interviewees found it difficult to do so in a
      representative way and empowering approach. Qualitative methods might capture
      best whether empowerment and participation have occurred in a programme. The
      positive experiences that the interviewees made with innovative qualitative
      methods encourage further investment in developing new research designs. 

PMID- 22987843
TI  - Enabling the powerful? Participatory action research with local policymakers and
      professionals for physical activity promotion with women in difficult life
      situations.
AB  - Enabling is a concept central to health promotion. It is perceived as a mechanism
      that can help people gain control over determinants of health. Little is known,
      however, about enabling among policy-makers and professionals. This case study
      investigates enabling among policy-makers and professionals who engaged in a
      specific participatory approach, cooperative planning. We define 'enabling' as
      creating action situations that allow policy-makers and professionals to (i)
      build individual capacities for health promotion and to (ii) apply these
      capacities to concrete organizational and political action at the institutional
      level. This case study followed policy-makers and professionals as they
      participated in a local physical activity promotion action research project in
      Germany. We conducted a secondary analysis of qualitative data gathered in that
      project (2005-2011). Methods included participant observation, document analysis,
      focus groups and qualitative interviews. All data were revisited for the case
      study and analyzed using qualitative content analysis. Findings include examples
      of enabling among policy-makers and professionals related to the cooperative
      planning process. Individual capacities were developed in perceived project
      roles, interactions with target groups and decision-making procedures. Findings
      also demonstrated municipal policy changes. Access to physical activity
      infrastructures improved, and an intersectoral job position was funded to support
      physical activity promotion among target group participants. Findings were
      analyzed using a model that links cooperative planning with a framework on policy
      change from a political science perspective. We conclude that cooperative
      planning might be a pathway to negotiated agreements that foster systematic
      enabling and health-promoting policy change. 

PMID- 22987844
TI  - 2012 Wayne Fenton Award for exceptional clinical care: Dr. Eadbhard O'Callaghan.

PMID- 22987845
TI  - Status of psychotic disorders in ICD-11.

PMID- 22987846
TI  - Treatment timing vs treatment type in first-episode psychosis: a paradigm shift
      in strategy and effectiveness.

PMID- 22987847
TI  - Implications of genetic findings for understanding schizophrenia.
AB  - From the perspective of those of us working on the genetics of schizophrenia,
      recent progress in identifying specific genetic risk factors at highly robust
      levels of statistical significance has been striking. However, the prevailing
      response among other schizophrenia researchers and some funders, families, and
      sufferers is often one of disappointment. In particular, it is often claimed that
      these discoveries explain only a small proportion of the genetic risk and hence
      tell us little about the nature of schizophrenia. The purpose of this article is
      to persuade you that recent genetic findings, while only revealing the tip of a
      complex genetic iceberg, already have profound implications for our general
      understanding of the classification and pathogenesis of schizophrenia and related
      disorders and that these have implications for schizophrenia research of all
      kinds.

PMID- 22987848
TI  - Cognitive behavior therapy versus other psychosocial treatments for
      schizophrenia.

PMID- 22987849
TI  - Twenty-five years of glutamate in schizophrenia: are we there yet?
AB  - At present, all medications for schizophrenia function primarily by blocking
      dopamine D2 receptors. Over 50 years ago, the first observations were made that
      subsequently led to development of alternative, glutamatergic conceptualizations.
      This special issue traces the historic development of the phencyclidine (PCP)
      model of schizophrenia from the initial description of the psychotomimetic
      effects of PCP in the early 1960s, through discovery of the link to N-methyl-D
      aspartate-type glutamate receptors (NMDAR) in the 1980s, and finally to the
      development of NMDA-based treatment strategies starting in the 1990s. NMDAR
      antagonists uniquely reproduce both positive and negative symptoms of
      schizophrenia, and induce schizophrenia-like cognitive deficits and
      neurophysiological dysfunction. At present, there remain several hypotheses
      concerning mechanisms by which NMDAR dysfunction leads to symptoms/deficits, and
      several theories regarding ideal NMDAR-based treatment approaches as outlined in
      the issue. Several classes of agent, including metabotropic glutamate agonists,
      glycine transport inhibitors, and D-serine-based compounds are currently in late
      stage clinical development and may provide long-sought treatments for persistent
      positive and negative symptoms and cognitive dysfunction in schizophrenia.

PMID- 22987850
TI  - NMDA receptor and schizophrenia: a brief history.
AB  - Although glutamate was first hypothesized to be involved in the pathophysiology
      of schizophrenia in the 1980s, it was the demonstration that N-methyl-D-aspartate
      (NMDA) receptor antagonists, the dissociative anesthetics, could replicate the
      full range of psychotic, negative, cognitive, and physiologic features of
      schizophrenia in normal subjects that placed the "NMDA receptor hypofunction
      hypothesis" on firm footing. Additional support came from the demonstration that
      a variety of agents that enhanced NMDA receptor function at the glycine
      modulatory site significantly reduced negative symptoms and variably improved
      cognition in patients with schizophrenia receiving antipsychotic drugs. Finally,
      persistent blockade of NMDA receptors recreates in experimental animals the
      critical pathologic features of schizophrenia including downregulation of 
      parvalbumin-positive cortical GABAergic neurons,  pyramidal neuron dendritic
      dysgenesis, and reduced spine density.

PMID- 22987856
TI  - Computer and statistical analysis of transcription factor binding and chromatin
      modifications by ChIP-seq data in embryonic stem cell.
AB  - Advances in high throughput sequencing technology have enabled the identification
      of transcription factor (TF) binding sites in genome scale. TF binding studies
      are important for medical applications and stem cell research. Somatic cells can
      be reprogrammed to a pluripotent state by the combined introduction of factors
      such as Oct4, Sox2, c-Myc, Klf4. These reprogrammed cells share many
      characteristics with embryonic stem cells (ESCs) and are known as induced
      pluripotent stem cells (iPSCs). The signaling requirements for maintenance of
      human and murine embryonic stem cells (ESCs) differ considerably. Genome wide
      ChIP-seq TF binding maps in mouse stem cells include Oct4, Sox2, Nanog, Tbx3,
      Smad2 as well as group of other factors. ChIP-seq allows study of new candidate
      transcription factors for reprogramming. It was shown that Nr5a2 could replace
      Oct4 for reprogramming. Epigenetic modifications play important role in
      regulation of gene expression adding additional complexity to transcription
      network functioning. We have studied associations between different histone
      modification using published data together with RNA Pol II sites. We found strong
      associations between activation marks and TF binding sites and present it
      qualitatively. To meet issues of statistical analysis of genome ChIP-sequencing
      maps we developed computer program to filter out noise signals and find
      significant association between binding site affinity and number of sequence
      reads. The data provide new insights into the function of chromatin organization
      and regulation in stem cells.

PMID- 22987857
TI  - Imaging of ex vivo nonmelanoma skin cancers in the optical and terahertz spectral
      regions optical and terahertz skin cancers imaging.
AB  - We tested the hypothesis that polarization sensitive optical and terahertz
      imaging may be combined for accurate nonmelanoma skin cancer (NMSC) delineation.
      Nine NMSC specimens were imaged. 513 MUm and 440 nm wavelengths were used for
      terahertz and optical imaging, respectively. Histopathology was processed for
      evaluation. Terahertz reflectance of NMSC was quantified. Our results demonstrate
      that cross-polarized terahertz images correctly identified location of the
      tumours, whereas cross-polarized and polarization difference optical images
      accurately presented morphological features. Cross-polarized terahertz images
      exhibited lower reflectivity values in cancer as compared to normal tissue.
      Combination of optical and terahertz imaging shows promise for intraoperative
      delineation of NMSC.

PMID- 22987851
TI  - Has an angel shown the way? Etiological and therapeutic implications of the
      PCP/NMDA model of schizophrenia.
AB  - Over the last 20 years, glutamatergic models of schizophrenia have become
      increasingly accepted as etiopathological models of schizophrenia, based on the
      observation that phencyclidine (PCP) induces a schizophrenia-like psychosis by
      blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate
      receptors. This article reviews developments in two key predictions of the model:
      first, that neurocognitive deficits in schizophrenia should follow the pattern of
      deficit predicted based on underlying NMDAR dysfunction and, second, that agents
      that stimulate NMDAR function should be therapeutically beneficial. As opposed to
      dopamine receptors, NMDAR are widely distributed throughout the brain, including
      subcortical as well as cortical brain regions, and sensory as well as association
      cortex. Studies over the past 20 years have documented severe sensory dysfunction
      in schizophrenia using behavioral, neurophysiological, and functional brain
      imaging approaches, including impaired generation of key sensory-related
      potentials such as mismatch negativity and visual P1 potentials. Similar deficits
      are observed in humans following administration of NMDAR antagonists such as
      ketamine in either humans or animal models. Sensory dysfunction, in turn,
      predicts impairments in higher order cognitive functions such as auditory or
      visual emotion recognition. Treatment studies have been performed with compounds
      acting directly at the NMDAR glycine site, such as glycine, D-serine, or D
      cycloserine, and, more recently, with high-affinity glycine transport inhibitors
      such as RG1678 (Roche). More limited studies have been performed with compounds
      targeting the redox site. Overall, these compounds have been found to induce
      significant beneficial effects on persistent symptoms, suggesting novel
      approaches for treatment and prevention of schizophrenia.

PMID- 22987858
TI  - Caring for a loved one with Alzheimer's disease: views from the population about
      hiring a health care advocate.
AB  - OBJECTIVE: Alzheimer's disease (AD) is associated with considerable caregiver and
      social burden. It is important to examine ways to minimize the negative effects
      of AD. Health care advocates (HCAs) may be one means of limiting the aversive
      effects of AD. METHOD: Participants completed a short survey that assessed their
      perceptions of the impact of comorbid AD on health status and their likelihood of
      hiring an HCA to assist in managing it. A mediational model was proposed:
      cognitive status (AD vs cognitively healthy) was the independent variable,
      perception of severity was the mediator, and the probability of hiring an HCA was
      the dependent variable. RESULTS: The results indicated that the relationship
      between cognitive status and probability of hiring an HCA was fully mediated by
      perceptions of severity. CONCLUSION: This study demonstrated that participants
      appreciated the impact of AD on health status, and this translated into a greater
      probability of hiring an HCA.

PMID- 22987859
TI  - An ignition key for atomic-scale engines.
AB  - A current-carrying resonant nanoscale device, simulated by non-adiabatic
      molecular dynamics, exhibits sharp activation of non-conservative current-induced
      forces with bias. The result, above the critical bias, is generalized rotational
      atomic motion with a large gain in kinetic energy. The activation exploits sharp
      features in the electronic structure, and constitutes, in effect, an ignition key
      for atomic-scale motors. A controlling factor for the effect is the non
      equilibrium dynamical response matrix for small-amplitude atomic motion under
      current. This matrix can be found from the steady-state electronic structure by a
      simpler  static calculation, providing a way to detect the likely appearance, or
      otherwise, of non-conservative dynamics, in advance of real-time modelling.

PMID- 22987860
TI  - Localization-delocalization transition for disordered cubic harmonic lattices.
AB  - We study numerically the disorder-induced localization-delocalization phase
      transitions that occur for mass and spring constant disorder in a three
      dimensional cubic lattice with harmonic couplings. We show that, while the phase
      diagrams exhibit regions of stable and unstable waves, the universality of the
      transitions is the same for mass and spring constant disorder throughout all the
      phase boundaries. The combined value for the critical exponent of the
      localization lengths of nu = 1.550(-0.017)(+0.020) confirms the agreement with
      the universality class of the standard electronic Anderson model of localization.
      We further support our investigation with studies of the density of states, the
      participation numbers and wave function statistics.

PMID- 22987861
TI  - Fatalism and its implications for risky road use and receptiveness to safety
      messages: a qualitative investigation in Pakistan.
AB  - Given the increasing vehicle numbers and expanding road construction in
      developing countries, the importance of safe road user behaviour is critical.
      Road traffic crashes (RTCs) are a significant problem in Pakistan; however, the
      factors that contribute to RTCs in Pakistan are not well researched. Fatalistic
      beliefs are a potential barrier to the enhancement of road safety, especially
      participation in health-promoting and injury prevention behaviours, and also
      contribute to risk taking. Fatalistic beliefs relating to road safety have been
      found in some developing countries, although research is scarce and indicates
      that the nature and extent of fatalism differs in each country. Qualitative
      research was undertaken with a range of drivers, religious orators, police and
      policy makers to explore associations between fatalism, risky road use and
      associated issues. Findings indicate that fatalistic beliefs are pervasive in
      Pakistan, are strongly linked with religion, present a likely barrier to road
      safety messages and contribute to risky road use. Fatalism appears to be a
      default attribution of RTC and the intensity of belief in fate surpasses the
      kinds of fatalism noted in the limited existing literature. These findings have
      importance to developing road safety countermeasures in countries where
      fatalistic beliefs are strong.

PMID- 22987862
TI  - Developing web-based training for public health practitioners: what can we learn
      from a review of five disciplines?
AB  - During a time when governmental funding, resources and staff are decreasing and
      travel restrictions are increasing, attention to efficient methods of public
      health workforce training is essential. A literature review was conducted to
      inform the development and delivery of web-based trainings for public health
      practitioners. Literature was gathered and summarized from five disciplines:
      Information Technology, Health, Education, Business and Communications, following
      five research themes: benefits, barriers, retention, promotion and evaluation. As
      a result, a total of 138 articles relevant to web-based training design and
      implementation were identified. Key recommendations emerged, including the need
      to conduct formative research and evaluation, provide clear design and layout,
      concise content, interactivity, technical support, marketing and promotion and
      incentives. We conclude that there is limited application of web-based training
      in public health. This review offers an opportunity to learn from other
      disciplines. Web-based training methods may prove to be a key training strategy
      for reaching our public health workforce in the environment of limited resources.

PMID- 22987863
TI  - What might work? Exploring the perceived feasibility of strategies to promote
      physical activity among women living in socioeconomically disadvantaged
      neighbourhoods.
AB  - This study aimed to investigate preferences for, perceived feasibility of and
      barriers to uptake of hypothetical physical activity promotion strategies among
      women from socioeconomically disadvantaged neighbourhoods. Semi-structured
      interviews were conducted with 20 purposively recruited women (18-45 years)
      living in socioeconomically disadvantaged urban and rural areas of Victoria,
      Australia. Participants indicated the most and least appealing of nine
      hypothetical strategies, strategies most likely to use and strategies most likely
      to increase physical activity. Interviews were digitally recorded and transcribed
      verbatim. Thematic and interpretive content analyses were used to identify
      emergent common and contrasting themes. A community centre-based program with
      free childcare, the provision of a cleaner while physical activity is undertaken
      and a neighbourhood-based program were the three most popular strategies. Mobile
      telephone-delivered text messages, an online interactive diary and subsidized gym
      memberships were considered least useful. Irrespective of the strategy,
      components of importance commonly identified were social support; being
      accountable to someone; having the option of a structured or flexible attendance
      design; integration of multiple strategies and financial considerations. Issues
      around trust and privacy and weight loss also emerged as important. The findings
      provide important insights for the development of physical activity programs
      targeting socioeconomically disadvantaged women.

PMID- 22987865
TI  - Metastable C-centered orthorhombic Si8 and Ge8.
AB  - A theoretical prediction on the structural stabilities, mechanical properties,
      and electronic properties of the C-centered orthorhombic (Cco) Si(8) and Ge(8) is
      presented, inspired by a recently proposed carbon allotrope structure, Cco-C(8).
      Energetically comparable with previously known metastable phases, Cco-Si(8) and
      Cco-Ge(8) may be obtained by decompressing the high-pressure beta-Sn phases, or
      by compressing the corresponding nanotubes. The calculated bulk moduli of Cco
      Si(8) and Cco-Ge(8) are close to those of the diamond phases. Further study of
      the electronic properties reveals that the band gaps of Cco-Si(8) and Cco-Ge(8)
      are tunable with variations in lattice parameters.

PMID- 22987864
TI  - Associations between hookah tobacco smoking knowledge and hookah smoking behavior
      among US college students.
AB  - Hookah tobacco smoking is increasing among US college students, including those
      who would not otherwise use tobacco. Part of hookah's appeal is attributed to the
      perception that hookah is less harmful than cigarettes. The aims of this study
      were to assess knowledge of harmful exposures associated with hookah smoking
      relative to cigarette smoking and to determine associations between this
      knowledge and hookah smoking outcomes. Students (N = 852) at the University of
      Florida were randomly sampled via e-mail to obtain information on demographics,
      hookah smoking behavior and knowledge of five exposures (e.g. tar and nicotine).
      Multivariable logistic regression models assessed independent associations
      between knowledge and hookah smoking outcomes. Of the five factual knowledge
      items asked, 475 (55.8%) of the respondents answered none correctly. In
      multivariable models, correct responses to any knowledge items were not
      associated with lower odds of hookah smoking or susceptibility to hookah smoking
      in the future. Although college students are largely unaware of the toxicant
      exposures associated with hookah smoking, there is little association between
      knowledge and hookah smoking behavior.

PMID- 22987866
TI  - Luminescence of impurity-bound excitons in Li6GdB3O9:Ce3+ single crystals.
AB  - The anomalous (tau < 10 ns) luminescence of wide bandgap crystals of lithium
      gadolinium orthoborate Li(6)GdB(3)O(9) doped with trivalent cerium ions, has been
      revealed for the first time and investigated through the low-temperature time
      resolved vacuum ultraviolet synchrotron spectroscopy. It was shown that the
      optical transitions at 6.2 eV are due to electron transfer from the ground 4f(1)
      states of Ce(3+) ion onto the autoionized states near the conduction band bottom
      of a crystal. These transitions lead to the formation of impurity-bound excitons
      in the form of correlated electron-hole pair, in which the hole component is
      localized at 4f-level of the cerium ion and an electron component is located at
      the conduction band bottom in the attractive potential of this hole. It is
      established that the direct radiative recombination of the cerium impurity-bound
      exciton leads to a fast broadband emission at 4.25 eV. The energy threshold for
      creation of the impurity-bound excitons was determined on the basis of the
      obtained spectroscopic data. We calculated the H(k) functions of distribution of
      the elementary relaxations over the reaction rate constants and explained on this
      basis the decay kinetics and quenching processes, not only for the anomalous
      emission at 4.25 eV, but for the ordinary 5d-4f luminescence at 3.0 eV in Ce(3+)
      ions. The paper discusses the decay channels for the impurity-bound excitons and
      their influence on the decay kinetics and spectra of luminescence in
      Li(6)GdB(3)O(9) crystals.

PMID- 22987867
TI  - Mixed modes of surface polaritons in a PML-type magnetoelectric multiferroic with
      canted spins.
AB  - We present a theoretical discussion of surface polaritons on a ferroelectric
      antiferromagnet with magnetoelectric coupling which allows the magnetic subsystem
      to be canted. Canting of the antiferromagnet results in weak ferromagnetism. The
      surface polaritons for a semi-infinite film are calculated for a propagation
      parallel to the uniaxial easy axis, leading to mixed modes. A superposition of
      two plane waves is needed to generate mixed surface modes. We find two branches,
      one near the magnon resonance frequency and the other near the phonon resonance
      frequency. We also find that the surface modes are non-reciprocal due to
      magnetoelectric interaction, such that omega(k) ? omega(-k), where omega is the
      frequency and k is the propagation vector.

PMID- 22987868
TI  - Magnetic and electronic properties of bulk and clusters of FePt L1(0).
AB  - An efficient tight-binding model including magnetism and spin-orbit interactions
      is extended to metallic alloys. The tight-binding parameters are determined from
      a fit to bulk ab initio calculations of each metal and rules are given to obtain
      the heteroatomic parameters. The spin and orbital magnetic moments as well as the
      magneto-crystalline anisotropy are derived. We apply this method to bulk FePt
      L1(0) and the results are compared with success to ab initio results where
      available. Finally this model is applied to a set of FePt L1(0) clusters and
      physical trends are derived.

PMID- 22987869
TI  - Sodium intake and blood pressure among US children and adolescents.
AB  - OBJECTIVE: To assess the association between usual dietary sodium intake and
      blood pressure among US children and adolescents, overall and by weight status.
      METHODS: Children and adolescents aged 8 to 18 years (n = 6235) who participated
      in NHANES 2003-2008 comprised the sample. Subjects' usual sodium intake was
      estimated by using multiple 24-hour dietary recalls. Linear or logistic
      regression was used to examine association between sodium intake and blood
      pressure or risk for pre-high blood pressure and high blood pressure (pre
      HBP/HPB). RESULTS: Study subjects consumed an average of 3387 mg/day of sodium,
      and 37% were overweight/obese. Each 1000 mg per day sodium intake was associated
      with an increased SD score of 0.097 (95% confidence interval [CI] 0.006-0.188,
      ~1.0 mm Hg) in systolic blood pressure (SBP) among all subjects and 0.141 (95%
      CI: -0.010 to 0.298, ~1.5 mm Hg) increase among overweight/obese subjects. Mean
      adjusted SBP increased progressively with sodium intake quartile, from 106.2 mm
      Hg (95% CI: 105.1-107.3) to 108.8 mm Hg (95% CI: 107.5-110.1) overall (P = .010)
      and from 109.0 mm Hg (95% CI: 107.2-110.8) to 112.8 mm Hg (95% CI: 110.7-114.9; P
      = .037) among those overweight/obese. Adjusted odds ratios comparing risk for pre
      HBP/HPB among subjects in the highest versus lowest sodium intake quartile were
      2.0 (95% CI: 0.95-4.1, P = .062) overall and 3.5 (95% CI: 1.3-9.2, P = .013)
      among those overweight/obese. Sodium intake and weight status appeared to have
      synergistic effects on risk for pre-HBP/HPB (relative excess risk for interaction
      = 0.29 (95% CI: 0.01-0.90, P < .05). CONCLUSIONS: Sodium intake is positively
      associated with SBP and risk for pre-HBP/HPB among US children and adolescents,
      and this association may be stronger among those who are overweight/obese.

PMID- 22987870
TI  - Water-absorbing balls: a "growing" problem.
AB  - Foreign body ingestion is a potentially serious clinical problem in children. We
      report a case of an 8-month-old infant who developed complete bowel obstruction
      requiring laparotomy due to ingestion of a superabsorbent polymer ball with
      advertised growth up to 400 times its original size. Most ingested foreign bodies
      that pass through the pylorus will make it safely through the gastrointestinal
      tract. This is not true for water-absorbing balls that progressively increase in
      size and cause intestinal obstruction. Other household products and toys on the
      market use a similar polymer-based water-absorbing technology, thus increasing
      the risk for accidental ingestion by young children. These rapidly expanding
      objects can cause significant morbidity, and timely diagnosis and treatment are
      prudent to improve patient outcomes.

PMID- 22987871
TI  - Improving delivery of EPSDT well-child care at acute visits in an academic
      pediatric practice.
AB  - BACKGROUND AND OBJECTIVE: Many patients with Medicaid do not receive timely,
      comprehensive well-child care through the Early and Periodic Screening,
      Diagnosis, and Treatment (EPSDT) program. Missed opportunities for EPSDT well
      child check-ups (WCCs) at acute visits contribute to this problem. The authors
      sought to reduce missed opportunities for WCCs at acute visits for patients
      overdue for those services. METHODS: A quality improvement team developed key
      drivers and used a people-process-technology framework to devise 3 interventions:
      (1) an electronic indicator based on novel definitions of EPSDT status (up-to
      date, due, overdue, no EPSDT), (2) a standardized scheduling process for acute
      visits based on EPSDT status, and (3) a dedicated nurse practitioner to provide
      WCCs at acute visits. Data were collected for 1 year after full implementation.
      RESULTS: At baseline, 10.3 acute visits per month were converted to WCCs. After
      intervention, 86.7 acute visits per month were converted. Of 13801 acute visits
      during the project, 31.2% were not up-to-date. Of those overdue for WCCs, 51.4%
      (n = 552) were converted to a WCC in addition to the acute visit. Including all
      patients who were not up-to-date, a total of 1047 acute visits (7.6% of all acute
      visits) were converted to comprehensive WCCs. Deferring needed WCCs at acute
      visits resulted in few patients who scheduled or completed future WCC visits.
      CONCLUSIONS: Implementation of interventions focused on people-process-technology
      significantly increased WCCs at acute visits within a feasible and practical
      model that may be replicated at other academic general pediatrics practices.

PMID- 22987872
TI  - The relationship between motor coordination and intelligence across the IQ range.
AB  - OBJECTIVE: In both clinical practice and research, motor delay is understood to
      be explained, at least in part, by intellectual abilities; however, no data are
      available to operationalize these criteria to guide clinical decision making.
      This study provides data on IQ and motor skills in children to answer 3 research
      questions concerning the relationship between IQ and motor skill: (1) Can motor
      coordination impairment be explained in terms of general intellectual
      retardation? (2) What level of motor performance should be expected given the
      person's measured intelligence? (3) At what point are motor difficulties
      considered to be in excess of those usually associated with mental retardation?
      METHODS: IQ and motor skill data were analyzed from a group of 460 children
      identified with/without motor difficulties from both clinical and educational
      settings. RESULTS: Typical and atypical motor skill was seen at all IQ levels,
      19% of the variance in motor outcomes was explained by IQ scores, and for each SD
      lower IQ, a mean loss of 10 percentile motor points should be expected.
      CONCLUSIONS: Although individuals with a lower measured IQ more often showed
      poorer motor performance than those with a higher measured IQ, motor skill at all
      levels of proficiency was seen in all IQ categories. These findings have
      important implications for clinical judgments and decision-making, as well as for
      future research directions to further operationalize the criteria relating to
      motor disorders in both the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Revision, and the International Classification of Diseases,
      10th Revision.

PMID- 22987873
TI  - Favorable outcome in a newborn with molybdenum cofactor type A deficiency treated
      with cPMP.
AB  - Molybdenum cofactor deficiency (MoCD) is a lethal autosomal recessive inborn
      error of metabolism with devastating neurologic manifestations. Currently,
      experimental treatment with cyclic pyranopterin monophosphate (cPMP) is available
      for patients with MoCD type A caused by a mutation in the MOCS-1 gene. Here we
      report the first case of an infant, prenatally diagnosed with MoCD type A, whom
      we started on treatment with cPMP 4 hours after birth. The most reliable method
      to evaluate neurologic functioning in early infancy is to assess the quality of
      general movements (GMs) and fidgety movements (FMs). After a brief period of
      seizures and cramped-synchronized GMs on the first day, our patient showed no
      further clinical signs of neurologic deterioration. Her quality of GMs was normal
      by the end of the first week. Rapid improvement of GM quality together with
      normal FMs at 3 months is highly predictive of normal neurologic outcome. We
      demonstrated that a daily cPMP dose of even 80 MUg/kg in the first 12 days
      reduced the effects of neurodegenerative damage even when seizures and cramped
      synchronized GMs were already present. We strongly recommend starting cPMP
      treatment as soon as possible after birth in infants diagnosed with MoCD type A.

PMID- 22987874
TI  - Electronic cigarette use among teenagers and young adults in Poland.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) are battery-powered devices
      developed with the goal of mimicking the action of smoking, including nicotine
      delivery, without the toxic effects of tobacco smoke. Little is known about the
      uptake of e-cigarettes among young people. METHODS: A survey was conducted with a
      cluster sample of 20240 students enrolled at 176 nationally representative Polish
      high schools and universities between September 2010 and June 2011. We estimated
      national e-cigarette prevalence among various demographic groups by using
      population weights. Multiple logistic regression was used to evaluate which
      demographic factors were independent predictors of 2 outcomes: ever use of e
      cigarettes and use in the previous 30 days. RESULTS: Among high school students,
      aged 15 to 19 years, 23.5% had ever used e-cigarettes and 8.2% had done so within
      the previous 30 days. Among those in universities, aged 20 to 24 years, 19.0% had
      ever used an e-cigarette and 5.9% had done so in the previous 30 days. In
      multivariate analyses that controlled for covariates, smoking cigarettes, male
      gender, living in an urban area, and having parents who smoke were associated
      with ever use of e-cigarettes. Overall, 3.2% of never smoking students reported
      ever use of e-cigarettes. CONCLUSIONS: About one-fifth of Polish youth have tried
      e-cigarettes; most of them had previously smoked cigarettes. It is unclear
      whether e-cigarettes are just a novelty that young people try only once or
      whether they have potential to compete in the marketplace with conventional
      cigarettes.

PMID- 22987875
TI  - Trends in venous thromboembolism-related hospitalizations, 1994-2009.
AB  - OBJECTIVE: Information on trends in venous thromboembolism (VTE) in US children
      is scant and inconsistent. We assessed national trends in VTE-associated
      pediatric hospitalizations. METHODS: All nonroutine newborn hospitalizations for
      children 0 to 17 years of age in the 1994-2009 Nationwide Inpatient Samples were
      included; routine newborn discharges were excluded. VTE diagnoses were identified
      by using the International Classification of Diseases, Ninth Revision, Clinical
      Modification codes. Variance weighted least square regression was used to assess
      trends in patient characteristics and rates of hospitalization per 100000
      population <18 years of age. Multivariable logistic regression models were used
      to estimate the probability of VTE diagnosis over the study period. RESULTS: The
      rate of VTE-associated hospitalization increased for all age subgroups (<1, 1-5,
      6-11, and 12-17 years), with the largest increase noted among children <1 year of
      age (from 18.1 per 100000 during 1994 to 49.6 per 100000 during 2009). Compared
      with 1994-1997, the adjusted odds of hospitalization with a VTE diagnosis were
      88% higher during 2006-2009 (adjusted odds ratio: 1.88 [95% confidence interval:
      1.64-2.17]). Venous catheter use, mechanical ventilation, malignancy,
      hospitalization >= 5 days, and VTE-related medical conditions were associated
      with increased likelihood of VTE diagnosis. CONCLUSIONS: The rate of VTE
      associated hospitalization among US children increased from 1994 through 2009.
      Increases in venous catheter procedures were associated with and may have
      contributed to the observed trends. The degree to which increased awareness of
      VTE influenced the temporal differences could not be determined.

PMID- 22987877
TI  - A new liquid human milk fortifier and linear growth in preterm infants.
AB  - OBJECTIVES: To evaluate the growth, tolerance, and safety of a new
      ultraconcentrated liquid human milk fortifier (LHMF) designed to provide optimal
      nutrients for preterm infants receiving human breast milk in a safe, nonpowder
      formulation. METHODS: Preterm infants with a body weight <= 1250 g fed expressed
      and/or donor breast milk were randomized to receive a control powder human milk
      fortifier (HMF) or a new LHMF for 28 days. When added to breast milk, the LHMF
      provided ~20% more protein than the control HMF. Weight, length, head
      circumference, and serum prealbumin, albumin, blood urea nitrogen, electrolytes,
      and blood gases were measured. The occurrence of sepsis, necrotizing
      enterocolitis, and serious adverse events were monitored. RESULTS: This
      multicenter, third party-blinded, randomized controlled, prospective study
      enrolled 150 infants. Achieved weight and linear growth rate were significantly
      higher in the LHMF versus control groups (P = .04 and 0.03, respectively). Among
      infants who adhered closely to the protocol, the LHMF had a significantly higher
      achieved weight, length, head circumference, and linear growth rate than the
      control HMF (P = .004, P = .003, P = .04, and P = .01, respectively). There were
      no differences in measures of feeding tolerance or days to achieve full feeding
      volumes. Prealbumin, albumin, and blood urea nitrogen were higher in the LHMF
      group versus the control group (all P < .05). There was no difference in the
      incidence of confirmed sepsis or necrotizing enterocolitis. CONCLUSIONS: Use of a
      new LHMF in preterm infants instead of powder HMF is safe. Benefits of LHMF
      include improvements in growth and avoidance of the use of powder products in the
      NICU.

PMID- 22987878
TI  - Variability of growth in children starting antiretroviral treatment in southern
      Africa.
AB  - BACKGROUND: Poor growth is an indication for antiretroviral therapy (ART) and a
      criterion for treatment failure. We examined variability in growth response to
      ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa.
      METHODS: Treatment naive children aged <10 years were included. We calculated
      weight for age z scores (WAZs), height for age z scores (HAZs), and weight for
      height z scores (WHZs) up to 3 years after starting ART, by using the World
      Health Organization standards. Multilevel regression models were used. RESULTS: A
      total of 17990 children (range, 238-8975) were followed for 36181 person-years.
      At ART initiation, most children were underweight (50%) and stunted (66%). Lower
      baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch
      up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated
      or reversed thereafter, whereas HAZ increased continuously over time. Three years
      after starting ART, WAZ ranged from -2.80 (95% confidence interval [CI]: -3.66 to
      -2.02) to -1.98 (95% CI: -2.41 to -1.48) in children with a baseline z score < -3
      and from -0.79 (95% CI: -1.62 to 0.02) to 0.05 (95% CI: -0.42 to 0.51) in
      children with a baseline WAZ >= -1. For HAZ, the corresponding range was -2.33
      (95% CI: -2.62 to -2.02) to -1.27 (95% CI: -1.58 to -1.00) for baseline HAZ < -3
      and -0.24 (95% CI: -0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ >= -1.
      CONCLUSIONS: Despite a sustained growth response and catch-up growth in children
      with advanced HIV disease treated with ART, normal weights and heights are not
      achieved over 3 years of ART.

PMID- 22987876
TI  - Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological
      development.
AB  - OBJECTIVE: To investigate whether circulating 25-hydroxyvitamin D(3) [25(OH)D(3)]
      concentration in pregnancy is associated with neuropsychological development in
      infants. METHODS: The Spanish population-based cohort study INfancia y Medio
      Ambiente Project recruited pregnant women during the first trimester of pregnancy
      between November 2003 and February 2008. Completed data on 1820 mother-infant
      pairs were used. Maternal plasma 25(OH)D(3) concentration was measured by high
      performance liquid chromatography in pregnancy (mean 13.5 +/- 2.1 weeks of
      gestation). Offspring mental and psychomotor scores were assessed by trained
      psychologists at age 14 months (range, 11-23) by using the Bayley Scales of
      Infant Development. beta-Coefficients with 95% confidence intervals (CIs) of
      mental and psychomotor scores associated with continuous or categorical
      concentrations of maternal plasma 25(OH)D(3) were calculated by using linear
      regression analysis. RESULTS: The median plasma value of 25(OH)D(3) in pregnancy
      was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship
      was found between circulating concentrations of maternal 25(OH)D(3)
      concentrations in pregnancy and mental and psychomotor scores in the offspring.
      After adjustment for potential confounders, infants of mothers with 25(OH)D(3)
      concentrations in pregnancy >30 ng/mL showed higher mental score (beta = 2.60;
      95% CI 0.63-4.56) and higher psychomotor score (beta = 2.32; 95% CI 0.36-4.28) in
      comparison with those of mothers with 25(OH)D(3) concentrations <20 ng/mL.
      CONCLUSIONS: Higher circulating concentration of maternal 25(OH)D(3) in pregnancy
      was associated with improved mental and psychomotor development in infants.

PMID- 22987880
TI  - Feasibility and preliminary outcomes of a scalable, community-based treatment of
      childhood obesity.
AB  - OBJECTIVE: Clinic-based treatments of childhood obesity are effective but
      typically have limited reach and are costly. In this study, we evaluated the
      effects of a scalable weight management program for children and teenagers.
      METHODS: Participants were 155 children and their parent/guardian. Children had a
      mean +/- SD age of 11.3 +/- 2.8 years, BMI z score of 2.23 +/- 0.41, and a
      percentage overweight of 72.5 +/- 34.0. Most (92%) were obese, and nearly half
      (46.5%) were >= 99th percentile for BMI. The primary outcome was change in
      percentage overweight from baseline to 6 months. RESULTS: At 6 months, children
      experienced a 3.4 percentage point reduction in percentage overweight (P = .001).
      Children <13 years had a 4.3 percentage point reduction in percentage overweight,
      whereas those >= 13 years had a 1.0 percentage point reduction. Those who
      attended a greater number of face-to-face group sessions experienced greater
      changes in percentage overweight. There were significant improvements in child
      health-related quality of life as reported by both children and their parents.
      CONCLUSIONS: These data suggest that a scalable, community-based pediatric
      obesity intervention can result in clinically significant reductions in
      percentage overweight, as well as improvements in health-related quality of life.

PMID- 22987879
TI  - Efficacy of family-based weight control program for preschool children in primary
      care.
AB  - OBJECTIVE: To test the efficacy of an innovative family-based intervention for
      overweight preschool-aged children and overweight parents conducted in the
      primary care setting. METHODS: Children with BMI >= 85th percentile and an
      overweight parent were randomized to intervention or information control (IC).
      Trained staff delivered dietary and physical/sedentary activities education to
      parents over 6 months (10 group meetings and 8 calls). Parents in the
      intervention received also behavioral modification. An intention-to-treat
      analysis was performed by using mixed analysis of variance models to test changes
      in child percent over BMI (%OBMI) and z-BMI and to explore potential moderators
      of group differences in treatment response. RESULTS: Ninety-six of 105 randomized
      families started the program: 46 children (31 girls/15 boys) in the intervention
      and 50 (33 girls/17 boys) in the IC, with 33 and 39 mothers and 13 and 11 fathers
      in intervention and IC, respectively. Baseline characteristics did not differ
      between groups. Children in the intervention group had greater %OBMI and z-BMI
      decreases at 3 and 6 months compared with those assigned to IC (P < .0021). A
      greater BMI reduction over time was also observed in parents in the intervention
      compared with parents assigned to IC (P < .0001). Child %OBMI and parent BMI
      changes were correlated (r = .31; P = .003). Children with greater baseline %OBMI
      were more likely to have a greater %OBMI decrease over time (P = .02).
      CONCLUSIONS: Concurrently targeting preschool-aged overweight youth and their
      overweight parents for behavioral weight control in a primary care setting
      reduced child %OBMI and parent BMI, with parent and child weight changes
      correlating.

PMID- 22987881
TI  - Pediatric residents' knowledge, use, and comfort with expedited partner therapy
      for STIs.
AB  - OBJECTIVE: We examined California pediatric residents' knowledge, practices, and
      comfort of providing expedited partner therapy (EPT) for sexually transmitted
      infections, by postgraduate year of training and presence of an adolescent
      medicine fellowship. We hypothesized that few residents are aware of EPT, and
      fewer are comfortable providing it; knowledge, practices, and comfort increase
      during residency; and presence of an adolescent medicine fellowship increases
      knowledge, practices, and comfort. METHODS: Online anonymous questionnaires were
      completed by pediatric residents from 14 California programs. RESULTS: Two
      hundred eighty-nine pediatric residents (41% response; mean age, 29.4 +/- 2.7
      years; 78% female) responded. Twenty-two percent reported being moderately or
      very familiar with EPT. Most correctly identified several EPT methods.
      Incorrectly identified as EPT included patient (55%), health department (42%),
      and provider (37%) referrals. Only 8% were aware of California's legal status
      regarding EPT. Sixty-nine percent knew that California law allows EPT for
      chlamydia and gonorrhea, but 38% incorrectly stated that EPT can be used to treat
      trichomoniasis. Fifty-two percent reported ever providing EPT, but 30% of them
      were uncomfortable doing so. Postgraduate year 1 residents were significantly
      more likely to report lack of experience as a barrier to prescribing EPT.
      Residents in programs with the presence of an adolescent medicine fellowship had
      significantly higher global knowledge scores and were more likely to practice EPT
      with fewer concerns. CONCLUSIONS: California pediatric residents have knowledge
      gaps and discomfort providing EPT, and the presence of adolescent medicine
      fellowship is associated with increased EPT knowledge, use, and comfort among
      residents. Our findings demonstrate a need to improve EPT education in pediatric
      residencies.

PMID- 22987882
TI  - Sexually explicit cell phone messaging associated with sexual risk among
      adolescents.
AB  - OBJECTIVES: Sexting (sending/receiving sexually explicit texts and images via
      cell phone) may be associated with sexual health consequences among adolescents.
      However, to date, no published data from a probability-based sample has examined
      associations between sexting and sexual activity. METHODS: A probability sample
      of 1839 students was collected alongside the 2011 Youth Risk Behavior Survey in
      Los Angeles high schools. Logistic regressions were used to assess the correlates
      of sexting behavior and associations between sexting and sexual risk-taking.
      RESULTS: Fifteen percent of adolescents with cell phone access reported sexting,
      and 54% reported knowing someone who had sent a sext. Adolescents whose peers
      sexted were more likely to sext themselves (odds ratio [OR] = 16.87, 95%
      confidence interval [CI]: 9.62-29.59). Adolescents who themselves sexted were
      more likely to report being sexually active (OR = 7.17, 95% CI: 5.01-10.25).
      Nonheterosexual students were more likely to report sexting (OR = 2.74, 95% CI:
      1.86-4.04), sexual activity (OR = 1.52, 95% CI: 1.07-2.15), and unprotected sex
      at last sexual encounter (OR = 1.84, 95% CI: 1.17-2.89). CONCLUSIONS: Sexting,
      rather than functioning as an alternative to "real world" sexual risk behavior,
      appears to be part of a cluster of risky sexual behaviors among adolescents. We
      recommend that clinicians discuss sexting as an adolescent-friendly way of
      engaging patients in conversations about sexual activity, prevention of sexually
      transmitted infections, and unwanted pregnancy. We further recommend that
      discussion about sexting and its associated risk behavior be included in school
      based sexual health curricula.

PMID- 22987883
TI  - Hypertension screening during ambulatory pediatric visits in the United States,
      2000-2009.
AB  - BACKGROUND AND OBJECTIVE: Hypertension occurs in 2% to 5% of children in the
      United States, and its prevalence has increased during the obesity epidemic.
      There is no consensus among professional organizations about how frequently blood
      pressure should be measured in children >3 years old. The purpose of this study
      was to estimate the frequency of hypertension screening during ambulatory
      pediatric visits in the United States and to determine patient- and provider
      level factors associated with screening during visits specifically for preventive
      care. METHODS: We analyzed data from a nationally representative sample of
      ambulatory visits by using the National Ambulatory Medical Care Survey and the
      National Hospital Ambulatory Medical Care Survey from 2000 through 2009. In the
      subset of visits involving patients aged 3 to 18 years, we estimated the
      frequency of screening during all visits, preventive visits, and preventive
      visits in which overweight/obesity was diagnosed. We used multivariable logistic
      regression to identify patient- and provider-level factors associated with
      screening. RESULTS: Hypertension screening occurred during 35% of ambulatory
      pediatric visits, 67% of preventive visits, and 84% of preventive visits in which
      overweight/obesity was diagnosed. Between 2000 and 2009, the frequency of
      screening increased in all visits and in preventive visits. Factors independently
      associated with screening included older age and overweight/obesity diagnosis.
      CONCLUSIONS: Providers do not measure blood pressure in two-thirds of pediatric
      visits and one-third of pediatric preventive visits. Providers may understand the
      importance of screening among overweight/obese children; however, efforts to
      encourage routine screening, particularly in young children, may be needed.

PMID- 22987886
TI  - Short report: Improving record-review surveillance of young children with an
      autism spectrum disorder.
AB  - INTRODUCTION: Records-based autism spectrum disorder surveillance developed at
      the Centers for Disease Control and Prevention has been extended to younger
      cohorts, although the utility of additional record sources has not been examined.
      We therefore conducted a pilot project to describe whether Centers for Disease
      Control and Prevention surveillance could identify younger children with an
      autism spectrum disorder evaluated as part of an ongoing screening study at
      Georgia State University. METHODS: In all, 31 families of children who screened
      positive for autism spectrum disorder and received a clinical evaluation at
      Georgia State University agreed to participate in the project. Of these, 10
      children lived inside the surveillance area and had records abstracted and
      reviewed for this project. Centers for Disease Control and Prevention
      surveillance results (i.e. autism spectrum disorder or non-autism spectrum
      disorder) were compared with Georgia State University evaluation results (i.e.
      autism spectrum disorder or non-autism spectrum disorder). RESULTS: In all, 4 of
      the 10 children were diagnosed with an autism spectrum disorder after the Georgia
      State University evaluation. None of the 4 children with an autism spectrum
      disorder were identified by current Centers for Disease Control and Prevention
      surveillance methods but all 4 children were identified by Centers for Disease
      Control and Prevention surveillance methods when additional record sources were
      included (i.e. records from the statewide early intervention program and Georgia
      State University evaluation). CONCLUSION: These findings suggest that partnering
      with early intervention programs and encouraging early autism spectrum disorder
      screening might improve autism spectrum disorder surveillance among young
      children.

PMID- 22987884
TI  - Misexpression of a chloroplast aspartyl protease leads to severe growth defects
      and alters carbohydrate metabolism in Arabidopsis.
AB  - The crucial role of carbohydrate in plant growth and morphogenesis is widely
      recognized. In this study, we describe the characterization of nana, a dwarf
      Arabidopsis (Arabidopsis thaliana) mutant impaired in carbohydrate metabolism. We
      show that the nana dwarf phenotype was accompanied by altered leaf morphology and
      a delayed flowering time. Our genetic and molecular data indicate that the
      mutation in nana is due to a transfer DNA insertion in the promoter region of a
      gene encoding a chloroplast-located aspartyl protease that alters its pattern of
      expression. Overexpression of the gene (oxNANA) phenocopies the mutation. Both
      nana and oxNANA display alterations in carbohydrate content, and the extent of
      these changes varies depending on growth light intensity. In particular, in low
      light, soluble sugar levels are lower and do not show the daily fluctuations
      observed in wild-type plants. Moreover, nana and oxNANA are defective in the
      expression of some genes implicated in sugar metabolism and photosynthetic light
      harvesting. Interestingly, some chloroplast-encoded genes as well as genes whose
      products seem to be involved in retrograde signaling appear to be down-regulated.
      These findings suggest that the NANA aspartic protease has an important
      regulatory function in chloroplasts that not only influences photosynthetic
      carbon metabolism but also plastid and nuclear gene expression.

PMID- 22987885
TI  - Crystal structures of Physcomitrella patens AOC1 and AOC2: insights into the
      enzyme mechanism and differences in substrate specificity.
AB  - In plants, oxylipins regulate developmental processes and defense responses. The
      first specific step in the biosynthesis of the cyclopentanone class of oxylipins
      is catalyzed by allene oxide cyclase (AOC) that forms cis(+)-12-oxo-phytodienoic
      acid. The moss Physcomitrella patens has two AOCs (PpAOC1 and PpAOC2) with
      different substrate specificities for C18- and C20-derived substrates,
      respectively. To better understand AOC's catalytic mechanism and to elucidate the
      structural properties that explain the differences in substrate specificity, we
      solved and analyzed the crystal structures of 36 monomers of both apo and ligand
      complexes of PpAOC1 and PpAOC2. From these data, we propose the following
      intermediates in AOC catalysis: (1) a resting state of the apo enzyme with a
      closed conformation, (2) a first shallow binding mode, followed by (3) a tight
      binding of the substrate accompanied by conformational changes in the binding
      pocket, and (4) initiation of the catalytic cycle by opening of the epoxide ring.
      As expected, the substrate dihydro analog cis-12,13S-epoxy-9Z,15Z-octadecadienoic
      acid did not cyclize in the presence of PpAOC1; however, when bound to the
      enzyme, it underwent isomerization into the corresponding trans-epoxide. By
      comparing complex structures of the C18 substrate analog with in silico modeling
      of the C20 substrate analog bound to the enzyme allowed us to identify three
      major molecular determinants responsible for the different substrate
      specificities (i.e. larger active site diameter, an elongated cavity of PpAOC2,
      and two nonidentical residues at the entrance of the active site).

PMID- 22987887
TI  - To enforce or not to enforce? The use of collaborative interfaces to promote
      social skills in children with high functioning autism spectrum disorder.
AB  - The goal of this stud was to examine whether a technological touch activated
      Collaborative Puzzle Game (CPG) increased positive social behaviors in children
      with high functioning autism spectrum disorder (HFASD). The CPG involved
      construction of a virtual puzzle by selecting and dragging pieces into the
      solution area on a touch screen table. The target picture was presented on the
      top of the screen. Six dyads of children with HFASD (aged 8-11 years) engaged in
      the CPG in a Free Play (FP) mode in which partners could independently move
      puzzle pieces versus in an Enforced Collaboration (EC) mode in which partners
      could only move puzzle pieces together. Videos of the dames were coded for the
      frequencies of positive and negative social interaction, affect, play, and
      autistic behaviors. Parents completed the Social Responsiveness Scale (SRS).
      Wilcoxon Signed-ranks tests indicated that children with HFASD showed
      significantly higher frequencies of positive social interaction and collaborative
      play in the EC versus FP modes but there were no differences in negative social
      behaviors. Differences in social behaviors between partners during the puzzle
      games were not significant; however there were differences within pair in the
      severity of social deficits as assessed by the SRS questionnaire. The CPG in an
      EC mode was effective in promoting positive social interaction by requiring
      children to work together towards a mutual goal. However, the increased challenge
      in this mode, particularly for children with lower social-communication skills,
      suggests the need for establishing selection criteria and mediation steps for
      such interventions.

PMID- 22987888
TI  - Reduced accuracy and sensitivity in the perception of emotional facial
      expressions in individuals with high autism spectrum traits.
AB  - Autism spectrum disorder (ASD) is among other things characterized by specific
      impairments in emotion processing. It is not clear, however, to what extent the
      typical decline in affective functioning is related to the specific autistic
      traits. We employed The Autism Spectrum-Quotient (AQ) to quantify autistic traits
      in a group of 500 healthy individuals and investigate whether we could detect
      similar difficulties in the perception of emotional expressions in a broader
      autistic phenotype. The group with high AQ score was less accurate and needed
      higher emotional content to recognize emotions of anger, disgust, and sadness.
      Our findings demonstrate a selective impairment in identification of emotional
      facial expressions in healthy individuals that is primarily related to the extent
      of autistic traits. 

PMID- 22987889
TI  - Social cognition, social skill, and the broad autism phenotype.
AB  - Social-cognitive deficits differentiate parents with the "broad autism phenotype"
      from non-broad autism phenotype parents more robustly than other
      neuropsychological features of autism, suggesting that this domain may be
      particularly informative for identifying genetic and brain processes associated
      with the phenotype. The current study examined whether the social-cognitive
      deficits associated with the broad autism phenotype extend to the general
      population and relate to reduced social skill. A total of 74 undergraduates
      completed the Broad Autism Phenotype Questionnaire, three standardized social
      cognitive tasks, and a live social interaction with an unfamiliar research
      assistant. Social broad autism phenotype traits were significantly associated
      with deficits in social cognition and reduced social skill. In addition, the
      relationship between social broad autism phenotype traits and social skill was
      partially mediated by social cognition, suggesting that the reduced interpersonal
      ability associated with the broad autism phenotype occurs in part because of
      poorer social-cognitive ability. Together, these findings indicate that the
      impairments in social cognition and social skill that characterize autism
      spectrum disorder extend in milder forms to the broad autism phenotype in the
      general population and suggest a framework for understanding how social broad
      autism phenotype traits may manifest in diminished social ability. 

PMID- 22987890
TI  - Diseases of the gastrointestinal tract in individuals diagnosed as children with
      atypical autism: a Danish register study based on hospital diagnoses.
AB  - The purpose of this study is to compare the prevalence and types of diseases
      (International classification of mental and behavioural disorders, 10th edition
      codes K20-K93) relating to the gastrointestinal tract in a clinical sample of 89
      individuals diagnosed as children with atypical autism/pervasive developmental
      disorder not otherwise specified with 258 controls from the general population.
      All participants were screened through the nationwide Danish National Hospital
      Register. The average observation time was 32.9 years, and mean age at the end of
      the observation period was 48.5 years. Among the 89 cases with atypical autism, a
      total of 22 (24.7%) were registered with at least one diagnosis of any disease of
      the gastrointestinal tract, against 47 of 258 (18.2%) in the comparison group (p
      = 0.22; odds ratio = 1.5; 95% confidence interval = 0.8-2.6). Without reaching
      statistical significance, the rate of diseases of the gastrointestinal tract was
      particularly high (odds ratio = 1.2) in those with intelligence quotient < 70.
      Overall, people with atypical autism had about the same frequency of gastric,
      intestinal and hepatic diseases as had controls.

PMID- 22987891
TI  - Motor proficiency and physical fitness in adolescent males with and without
      autism spectrum disorders.
AB  - This study compared components of motor proficiency and physical fitness in
      adolescents with and without autism spectrum disorders, and assessed the
      associations between the two measures within each group. A total of 62 adolescent
      males with (n = 31) and without (n = 31) autism spectrum disorders aged 10-17
      years completed the Bruininks-Oseretsky Test of Motor Proficiency (2nd ed.), the
      BROCKPORT Physical Fitness Test, and the bioelectrical impedance analysis. The
      main findings are as follows: (1) adolescents with autism spectrum disorders had
      significantly lower scores on all motor proficiency and fitness measures, except
      body composition, than adolescents without autism spectrum disorders and that (2)
      the types of associations between the two measures differed significantly across
      the groups. Specific interventions to maximize motor proficiency and physical
      fitness in adolescents with autism spectrum disorders are urgently needed. 

PMID- 22987892
TI  - Adaptive function in preschoolers in relation to developmental delay and
      diagnosis of autism spectrum disorders: insights from a clinical sample.
AB  - This study aims to explore the relationship between developmental ability, autism
      and adaptive skills in preschoolers. Adaptive function was assessed in 152
      preschoolers with autism, with and without developmental delay, and without
      autism, with and without developmental delay. Their overall adaptive function,
      measured by the general adaptive composite on the Adaptive Behaviour Assessment
      System, was closely correlated to developmental ability as measured by the
      general quotient on the Griffith Mental Development Scales. Children with autism
      performed significantly less well on both scales. Domain scores discriminated
      between children with and without autism, with poorer performance on both the
      social and practical domain scores for children with autism, even when
      controlling for the effects of development. Children with average development,
      both with and without autism, had lower adaptive skills than expected for their
      developmental level. The importance of considering domain scores as well as the
      general adaptive composite when determining support needs is emphasised. 

PMID- 22987893
TI  - Spontaneous attention to faces in Asperger syndrome using ecologically valid
      static stimuli.
AB  - Previous eye tracking research on the allocation of attention to social
      information by individuals with autism spectrum disorders is equivocal and may be
      in part a consequence of variation in stimuli used between studies. The current
      study explored attention allocation to faces, and within faces, by individuals
      with Asperger syndrome using a range of static stimuli where faces were either
      viewed in isolation or viewed in the context of a social scene. Results showed
      that faces were viewed typically by the individuals with Asperger syndrome when
      presented in isolation, but attention to the eyes was significantly diminished in
      comparison to age and IQ-matched typical viewers when faces were viewed as part
      of social scenes. We show that when using static stimuli, there is evidence of
      atypicality for individuals with Asperger syndrome depending on the extent of
      social context. Our findings shed light on the previous explanations of gaze
      behaviour that have emphasised the role of movement in atypicalities of social
      attention in autism spectrum disorders and highlight the importance of
      consideration of the realistic portrayal of social information for future
      studies. 

PMID- 22987894
TI  - Referral pattern and special interests in children and adolescents with Asperger
      syndrome: a Turkish referred sample.
AB  - OBJECTIVES: To investigate the most frequent reasons for referral, the most
      common special interests, age at first referral to a mental health service, and
      the age of diagnosis in children and adolescents with Asperger syndrome living in
      Turkey. METHODS: This study includes 61 children and adolescents diagnosed with
      Asperger syndrome using strict DSM-IV criteria. RESULTS: The mean age at first
      referral was 7.9 whereas the mean age when Asperger syndrome was diagnosed was
      9.9, which is compatible with other studies. The most frequent reasons for the
      first referral were attention deficits, hyperactivity, and academic failure, and
      the most common special interest area was "electronic devices, computer, and
      technical interests". CONCLUSIONS: The types of special interests and referral
      reasons in our Asperger syndrome sample are very similar to the interest areas
      and referral reasons of individuals with Asperger syndrome from developed western
      countries indicating the universality of symptoms. It could be concluded that
      children and adolescents with Asperger syndrome may refer to mental health
      services with a variety of symptoms; therefore, it is important to make a
      detailed assessment of social difficulties especially in school-age children and
      adolescents for the differential diagnosis of Asperger syndrome.

PMID- 22987895
TI  - Relationship satisfaction, parenting stress, and depression in mothers of
      children with autism.
AB  - Mothers of children with autism report higher levels of depression than mothers
      of children with other developmental disabilities. We explored the relations
      between child characteristics of diagnostic severity and problem behaviors,
      parenting stress, relationship quality, and depressive symptoms in 70 mothers of
      young children with autism. We hypothesized that relationship quality and
      parenting stress would relate to maternal depression beyond contributions of
      child characteristics. Multiple regression analysis revealed a main effect of
      parenting stress above and beyond child problem behaviors and autism severity. A
      significant interaction emerged, with relationship quality buffering the effect
      of parenting stress on depression. Results suggest that the relation between
      child problem behaviors and maternal depression should be considered in
      conjunction with other measures of marriage and family stress. Relationship
      quality and parenting stress may also represent important factors to be
      explicitly considered within intervention paradigms for young children with
      autism spectrum disorders. 

PMID- 22987896
TI  - The distribution of and relationship between autistic traits and social anxiety
      in a UK student population.
AB  - Traits associated with autism and social anxiety were assessed in a UK student
      population (n = 1325) using the Autism-spectrum Quotient and the Liebowitz Social
      Anxiety Scale. Clinically relevant levels of autistic traits were observed in
      3.3% of the cohort; 10.1% of the cohort reported clinically relevant levels of
      social anxiety; 1.8% of the cohort met clinically relevant cut-offs for both
      conditions. There was a significant positive correlation between scores on the
      two scales (r = .51); students with high levels of autistic traits were more
      likely to report increased social anxiety than those with average or low levels
      of autistic traits. Level of social anxiety was best predicted by autistic traits
      associated with social skill, attention switching and communication, accounting
      for 33% of the variance in social anxiety scores. Social skill was a better
      predictor of social anxiety in males than females; attention switching ability
      was a better predictor of social anxiety in females than males. Students with
      high levels of autistic traits displayed heightened anxiety to situations and
      activities necessary for the successful completion of their degree. Implications
      for student well-being and attainment are discussed.

PMID- 22987897
TI  - A randomised group comparison controlled trial of 'preschoolers with autism': a
      parent education and skills training intervention for young children with
      autistic disorder.
AB  - AIM: To determine the effect of parent education on adaptive behaviour, autism
      symptoms and cognitive/language skills of young children with autistic disorder.
      METHOD: A randomised group comparison design involving a parent education and
      counselling intervention and a parent education and behaviour management
      intervention to control for parent skills training and a control sample. Two
      rural and two metropolitan regions were randomly allocated to intervention groups
      (n = 70) or control (n = 35). Parents from autism assessment services in the
      intervention regions were randomly allocated to parent education and behaviour
      management (n = 35) or parent education and counselling (n = 35). RESULTS: Parent
      education and behaviour management resulted in significant improvement in
      adaptive behaviour and autism symptoms at 6 months follow-up for children with
      greater delays in adaptive behaviour. Parent education and behaviour management
      was superior to parent education and counselling. We conclude that a 20-week
      parent education programme including skills training for parents of young
      children with autistic disorder provides significant improvements in child
      adaptive behaviour and symptoms of autism for low-functioning children.

PMID- 22987898
TI  - 2011: the scurvy Odyssey.
AB  - The authors report the case of a 50-year-old alcoholic man with chronic hepatitis
      C virus infection, who presented to the emergency department with fever and
      exuberant ecchymoses and petechiae on both legs. After a careful examination and
      laboratory assessment, the not-so-obvious hypothesis of scurvy was disclosed.
      Simply with vitamin C replacement and nutritional advice, a dramatic improvement
      in his condition was observed. In modern societies, a generalised access to food
      renders scurvy as a rare disease, often misdiagnosed. A multidisciplinary
      approach is emphasised as the key to a more simple differential diagnosis,
      avoiding unnecessary exams and preventing serious complications, or even death,
      if left untreated.

PMID- 22987899
TI  - Retrograde dissection during percutaneous coronary intervention: sealing of the
      entry site by covered stent implantation.
AB  - We present a case of iatrogenic aortic haematoma, developed during percutaneous
      coronary intervention, treated with covered stent implantation followed by a
      conservative approach characterised by the integration of both clinical and
      multimodal imaging information. This complication can lead to overt aortic
      dissection (28-47%), rupture (20-45%) or death (21%). In 10% of the cases it can
      completely regress. Guidelines for its treatment are debated because of the
      unpredictable natural history of intramural haematoma. Nowadays, a close follow
      up with multimodal imaging is considered a valid strategy for the appropriate
      management of this severe condition. On the basis of the patient's clinical
      condition and the information obtained by multiple imaging tests (angiography,
      transthoracic and transesophageal echocardiography and multidetector CT scan) we
      decided to treat our patient with medical therapy. To date, a 1-year follow-up
      negative for cardiac events is recorded.

PMID- 22987900
TI  - Severe primary hypothyroidism presenting with torsades de pointes.
AB  - An 85-year-old lady presented to our institution following multiple episodes of
      transient loss of consciousness. Her admission ECG revealed a junctional
      bradycardia with significant QT prolongation. Telemetry captured a torsades de
      pointes arrhythmia. Possible offending drugs (digoxin and hydroxychloroquine)
      were stopped and she was given intravenous magnesium and potassium. Despite this,
      she continued to have runs of torsades. An isoprenaline infusion was commenced to
      increase her resting heart rate. Her QT interval shortened and she had no further
      arrhythmia. Investigation into the cause of her bradycardia and prolonged QT
      revealed profound hypothyroidism. Levothyroxine was commenced but the patient
      remained bradycardia and required a permanent pacemaker. She had no further
      arrhythmia and was discharged home safely. This is a very rare case of severe
      primary hypothyroidism presenting with torsades de pointes.

PMID- 22987902
TI  - The Hummingbird sign: a diagnostic clue for Steele-Richardson-Olszweski syndrome.

PMID- 22987901
TI  - Primary total knee arthroplasty infected with Serratia marcescens.
AB  - We report an unusual case of a Serratia marcescens infection of total knee
      arthroplasty 4&emsp14;weeks after the procedure following aspiration carried out
      on the ward (contrary to local protocol). This was successfully treated with
      thorough wound debridement, irrigation, change of the polyethylene liner and
      systemic antibiotics using intravenous meropenem for 3&emsp14;weeks followed by
      oral ciprofloxacin for another 3&emsp14;weeks. Our patient made an uneventful
      recovery and there was no reported recurrence of infection at 8&emsp14;months of
      follow-up. We are unsure as to whether the infection was introduced at the time
      of the joint aspiration or was a complication of the initial procedure despite
      all the standard aseptic measures taken at the time of surgery.

PMID- 22987903
TI  - Penetrating intracranial gunshot wound transecting the right transverse sinus.
AB  - A 23-year-old man sustained a gunshot wound to the posterior head. Imaging
      demonstrated a transection of the right transverse sinus, a retained bullet
      fragment and significant cerebellar oedema. The patient emergently underwent
      suboccipital decompression associated with brisk bleeding from the transverse
      sinus. Reported examples of surgical management of cerebral venous sinuses
      include: packing, grafting, patching and ligation. Our patient had a codominant
      transverse sinus and underwent successful unilateral ligation. His postoperative
      course was uneventful, however, he did require a ventriculoperitoneal shunt. He
      was subsequently discharged to rehab with a favourable outcome.

PMID- 22987904
TI  - A novel false-positive cause in testis scintigraphy in the diagnosis of testis
      torsion.
AB  - Testis scintigraphy is the most reliable modality in the diagnosis of testis
      torsion since it directly reflects the vascularity of the testis. The 'rim sign'
      is considered as the pathognomonic sign of the missed torsion. However, there are
      some possible false-positive cases. In this case report, we would like to present
      an unexpected false-positive cause of the 'rim sign' in testis scintigraphy in an
      18-year-old male patient.

PMID- 22987905
TI  - Acquired methaemoglobinaemia related to phenazopyridine ingestion.
AB  - Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of
      haeme are oxidised to the ferric state. This results in increased affinity to the
      bound oxygen and decreasing its availability to tissues. Most cases of
      methaemoglobinaemia are acquired, resulting from an increased methaemoglobin
      formation by various exogenous agents. The authors report an elderly patient
      presenting to the emergency department with a 1-month history of shortness of
      breath. Around the same time she had started using over-the-counter (OTC)
      phenazopyridine tablets for urinary symptoms. The patient was hypoxic and
      cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The
      presence of abnormal haemoglobin was suspected and confirmed by elevated levels
      of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the
      methaemoglobinaemia, which the patient was not aware of. This case highlights the
      importance of always inquiring the OTC drug use especially in geriatric
      population.

PMID- 22987906
TI  - The lack of sleep, the pineal gland and breast cancer.

PMID- 22987907
TI  - Bilateral optic disc swelling as a presenting sign of superior sagittal sinus
      thrombosis.
AB  - The case of a 59-year-old Caucasian man who presented with a 6-week history of
      intermittent blurring of vision and diplopia is reported. Fundoscopy revealed
      asymmetrical, bilateral optic disc swelling with peripapillary haemorrhages. An
      initial CT scan and D-dimer level were reported as normal. A subsequent MRI
      revealed a recanalising superior sagittal sinus thrombosis. Cerebral venous sinus
      thrombosis is a rare and potentially fatal condition. The author suggests that it
      should be part of the differential diagnosis of bilateral optic disc swelling and
      that a normal unenhanced CT scan and D-dimer would not rule out this potentially
      devastating condition.

PMID- 22987908
TI  - Posterior reversible encephalopathy syndrome: the importance of early diagnosis.
AB  - A 14-year-old boy was submitted to cardiac transplant due to a dilated
      cardiomyopathy. On the fourth day of immunosuppression (corticosteroids,
      mycophenolate mofetil and tacrolimus), he developed right focal seizures and
      drowsiness. Blood pressure was in the normal range and laboratory findings in
      cerebral spinal fluid and blood were unremarkable, with drugs in non-toxic
      levels. The EEG showed a slow background rhythm more pronounced on the right and
      a seizure onset in the right occipital region. MRI revealed a diffuse
      hyperintense subcortical white-matter lesion on fluid attenuated inversion
      recovery, with lesser involvement of left temporal-occipital region. There was no
      enhancement with gadolinium and MRI diffusion-weighted imaging was consistent
      with vasogenic oedema. Tacrolimus was stopped with regression of MRI
      abnormalities and clinical recovery. Posterior reversible encephalopathy
      associated with tacrolimus is a rare but potentially serious complication of
      solid organ transplants. A prompt diagnosis and correct treatment is essential to
      avoid irreversible brain damage.

PMID- 22987909
TI  - Annular pancreas associated with duodenal obstruction.

PMID- 22987910
TI  - An unusual polyp at colonoscopy.

PMID- 22987911
TI  - Endometrial stromal sarcoma of uterus with metastasis to the lung and brain.
AB  - Endometrial stromal sarcomas are rare tumours of the uterus and account for 10%
      of uterine sarcomas. Most of such tumours are low grade, although even these
      types can spread to the extrauterine areas; however, brain metastasis is very
      uncommon. This case report presents a 43-year-old Iranian woman with synchronous
      lung and brain metastases.

PMID- 22987912
TI  - Ashwagandha root in the treatment of non-classical adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is a well-characterised family of disorders
      of the adrenal cortices, resulting in varying degrees of cortisol, aldosterone
      and androgen deficiency or androgen excess, depending on the enzyme(s) affected
      and the degree of quantitative or functional enzyme deficit. Withania somnifera
      (WS), commonly known as Ashwagandha, is a medicinal plant that has been employed
      for centuries in ayurvedic medicine. Preclinical studies have shown that WS
      increases circulating cortisol levels and improves insulin sensitivity. We report
      the case of a 57-year-old woman with non-classical adrenal hyperplasia due to
      both 3-beta-ol dehydrogenase deficiency and aldosterone synthase deficiency who
      was self-treated with WS for 6 months. After 6 months of treatment her serum 18
      OH-hydroxycorticoserone, 17-OH-pregnenolone, corticosterone and 11-deoxycortisol
      decreased by 31%, 66%, 69% and 55%, respectively. The biochemical improvement was
      accompanied by a noticeable reduction in scalp hair loss.

PMID- 22987913
TI  - Progressive gait instability in a young girl; what will happen at the end?

PMID- 22987914
TI  - Incidental finding of a large Morgagni's hernia in a 76-year-old lady.

PMID- 22987915
TI  - Graduated exposure and positive reinforcement to overcome setting and activity
      avoidance in an adolescent with autism.
AB  - Some students who have developmental disabilities avoid settings and activities
      that can improve their learning and quality of life. This two-phase study
      concerned an adolescent boy with autism who avoided the gross-motor exercise
      room, gymnasium, and music room at his school; he demonstrated distress,
      agitation, and problem behaviors when prompted to enter these areas. Using
      graduated exposure combined with positive reinforcement, he learned to enter
      these settings without resisting and eventually to participate in activities
      within the settings. This article discusses this intervention approach for
      reducing and eliminating avoidant behavior.

PMID- 22987916
TI  - Initial open trial of a computerized behavioral activation treatment for
      depression.
AB  - This article presents preliminary findings from use of a novel computer program
      that implements an evidence-based psychological intervention to treat depression
      based on behavioral activation (BA) therapy. The program is titled "Building a
      Meaningful Life Through Behavioral Activation". The findings derive from an open
      trial with moderate to severely depressed individuals (N = 15) in an Intention to
      Treat sample. Hierarchical linear modeling (HLM) analyses revealed significant
      change over time on Beck Depression Inventory-Second Edition (BDI-II) scores,
      Revised Hamilton Depression Rating Scale scores, and significant contribution to
      BDI-II score variance by participant age over time, change over time in negative
      automatic thoughts, and change over time in BA scores. Piecewise HLM analyses
      revealed that significant change over time was associated uniquely with active
      treatment and not during 3 weeks of baseline measurement. In addition to
      treatment-associated significant change on all dependent measures over time,
      effect sizes were in the moderate to large range. Limitations are small sample
      size, nonrandomized control, research-recruited patients instead of purely
      treatment-seeking patients, possible rating bias by independent assessors who had
      knowledge that participants had received active treatment in this open trial, and
      the influence of additional services received in the post acute-treatment phase
      by some participants could have contributed to maintenance of gains reported for
      that period.

PMID- 22987917
TI  - Evidence-based behavioral treatment of dog phobia with young children: two case
      examples.
AB  - Specific phobias are among the most common anxiety disorders, especially in
      children. Unfortunately, a paucity of literature exists regarding the treatment
      of specific phobia in young children, despite the knowledge that traditional
      techniques (i.e., cognitive-behavioral therapy [CBT]) may not be practical.
      Therefore, the purpose of this article is to present two case studies that
      provide empirical support for the evidence-based behavioral treatment of specific
      phobia with young children (ages 4 and 5 years). Results indicated that following
      10 to 13 sessions of graduated exposure therapy using reinforced practice and
      participant modeling, the children no longer met criteria for clinically
      significant phobias of dogs. Treatment effects were maintained at 7-month follow
      up despite reported lack of practice and/or regular exposure to dogs in the
      children's daily lives.

PMID- 22987918
TI  - Salt sensitivity of blood pressure is associated with polymorphisms in the sodium
      bicarbonate cotransporter.
AB  - Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of
      the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with
      hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with
      salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant
      diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of
      high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a >= 7-mm Hg
      increase in mean arterial pressure during a randomized transition between high
      and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were
      assayed, 25 of which were tested for association. Association analyses with salt
      sensitivity revealed 3 variants that associated with salt sensitivity, 2 in
      SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842
      and rs10177833) demonstrated highly significant results and large effects sizes,
      using logistic regression. These 2 SNPs had P values of 1.0 * 10(-4) and 3.1 *
      10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models,
      respectively, with the G allele at both sites conferring protection. These SNPs
      remained significant after adjusting for body mass index and age (P=8.9 * 10(-5)
      and 2.6 * 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the
      association of these SNPs with salt sensitivity was replicated in a second
      hypertensive population. Meta-analysis demonstrated significant associations of
      both SNPs with salt sensitivity (rs7571842 [P=1.2 * 10(-5)]; rs1017783 [P=1.1 *
      10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt
      sensitivity of blood pressure in 2 separate white populations.

PMID- 22987920
TI  - Urinary plasmin activates collecting duct ENaC current in preeclampsia.
AB  - In nephrotic syndrome, plasminogen is aberrantly filtered from plasma to the
      urinary space and activated along the tubular system. In vitro, plasmin increases
      ENaC current by proteolytic cleavage of the gamma-subunit. It was hypothesized
      that preeclampsia is associated with plasmin-dependent ability of tubular fluid
      to activate ENaC. Urine was sampled from 16 preeclamptic (PE) patients and 17
      normotensive pregnant women (Ctrl). Urine was analyzed for plasmin(ogen),
      creatinine, albumin, aldosterone, Na(+), K(+), proteolytic activity, and for its
      effect on inward current in cortical collecting duct cells (M1 cells) by whole
      cell patch clamp. In PE, urine plasmin(ogen): creatinine ratio was elevated 40
      fold (geometric mean, 160 versus 4 ug/g; P<0.0001) and urine aldosterone:
      creatinine ratio was suppressed to 25% of Ctrl (geometric mean, 27 versus 109
      ug/g; P<0.001). A significant negative correlation was found in PE between
      urinary plasmin(ogen) and aldosterone (P<0.05). In PE, proteolytic activity was
      detected at 90 to 75 kD by gelatin zymography in 14 of 16 patients and confirmed
      by serine protease assay. Immunoblotting showed active plasmin in PE urine. Whole
      cell inward current increased in M1 cells on exposure to urine from PE (173+/
      21%; n=6; P<0.001). The increase in current was abolished by amiloride (2
      MUmol/L; P<0.001), alpha(2)-antiplasmin (1 MUmol/L; P<0.001), and heat
      denaturation (P<0.001). Preeclampsia is associated with urinary excretion of
      plasmin(ogen) and plasmin-dependent activation of ENaC by urine. Proteolytic
      activation of ENaC by plasmin may contribute to Na(+) retention and hypertension
      in preeclampsia.

PMID- 22987919
TI  - Genetic variants in Arhgef11 are associated with kidney injury in the Dahl salt
      sensitive rat.
AB  - A previous genetic analysis comparing the Dahl salt-sensitive (S) rat with the
      spontaneously hypertensive rat identified a major locus on chromosome 2 that
      influences proteinuria in the S rat. In the present study, blood pressure,
      proteinuria, and renal hemodynamics were evaluated in congenic strains with small
      segments of the protective spontaneously hypertensive rat genome on the S
      background. Proteinuria and renal function were significantly improved in the
      congenic strains compared with the S. The causative locus interval was narrowed
      to <375 kb on the basis of congenic strains, haplotype data, comparative mapping,
      and concordance with human genetic studies. Sequencing of the coding region of
      genes in this region identified 36 single nucleotide polymorphisms (13
      nonsynonymous and 23 synonymous). Gene expression profiling indicated that only a
      few genes exhibited differential expression. Arhgef11, Pear1, and Sh2d2 were
      identified as important candidate genes that may be linked to kidney injury in
      the S rat. In particular, Arhgef11 plays an important role in the activation of
      the Rho-ROCK signaling pathway. Inhibition of this pathway using fasudil resulted
      in a significant reduction of proteinuria in treated S rats (compared with
      untreated S). However, no difference was observed between treated or untreated
      spontaneously hypertensive rat or congenic strains. The homologous region in
      humans was found to be associated with estimated glomerular filtration rate in
      the Candidate Gene Association Resource population. In summary, these findings
      demonstrate that allelic variants in Arhgef11, acting through the Rho-ROCK
      pathway, could influence kidney injury in the S as well as provide insight into
      human kidney disease.

PMID- 22987921
TI  - Left ventricular mass and geometry in adolescence: early childhood determinants.
AB  - It is not known whether birth weight and early childhood growth are associated
      with the development of cardiac left ventricular mass (LVM) in healthy
      adolescents. Left ventricular growth and geometric remodeling may have long-term
      consequences on cardiovascular health later in life. We studied the determinants
      of LVM and patterns of geometric remodeling in adolescents with specific emphasis
      on birth size and growth in early childhood. Left ventricular measurements were
      obtained with echocardiography in 418 adolescents at the age of 15 years in a
      prospective atherosclerosis prevention study, Special Turku Coronary Risk Factor
      Intervention Project (STRIP). Birth weight (P=0.0004), current pulse pressure
      (P=0.013), physical activity level (P=0.0024), weight (P<0.0001), and male sex
      (P<0.001) had an independent direct association with LVM in adolescents
      explaining 47% of the variation. Growth in early childhood was not associated
      with LVM in adolescents. Birth weight (P=0.0066), current weight (P<0.0001), and
      physical activity level (P=0.0017) were directly associated with left ventricular
      posterior wall thickness. Current weight was also directly associated with septal
      thickness (P<0.0001). Boys had a thicker septum than girls (P=0.0092). Normal
      relative wall thickness and increased left ventricular mass index (eccentric
      remodeling) (P<0.0001), as well as increase in both variables (concentric,
      increased LVM) (P=0.0003), were associated with higher body mass index. Our
      results indicate that birth weight has a long-lasting impact on LVM and normal
      body weight is beneficial for cardiac structure in adolescents.

PMID- 22987922
TI  - MicroRNAs are involved in end-organ damage during hypertension.
AB  - Even in the new millennium, arterial hypertension remains a serious condition,
      with considerable morbidity and mortality worldwide. Crucial in managing the
      disease is not only lowering arterial blood pressure but also preventing or
      treating the typical end-organ damage caused by long-lasting and inadequately
      treated hypertension. In the past decade, it has been shown that microRNAs (miRs)
      are involved in several hypertension-related pathologies, such as cardiac
      hypertrophy and fibrosis, hypertensive heart failure, renal fibrosis, kidney
      failure, and, to a lesser extent, eye disease and hemorrhagic stroke. Whereas
      others extensively reviewed the role of miRs in atherosclerosis and vascular
      disease, this review focuses on their role in target organ damage during arterial
      hypertension. We emphasize the involvement of miRs in pathological end-organ
      remodeling processes and try to demonstrate some common miR signatures in
      distinct end organs. Hence, we aimed to provide proof of arterial hypertension
      being a systemic disease, similar to diabetes mellitus or metabolic syndrome.
      Furthermore, miRs that act on one particular process in different end organs are
      interesting therapeutic targets. Some future perspectives in miR research are
      highlighted with respect to novel therapeutic strategies in the cardiovascular
      field.

PMID- 22987924
TI  - Dairy consumption and incidence of hypertension: a dose-response meta-analysis of
      prospective cohort studies.
AB  - Observational and clinical studies suggest that dairy intake, particularly low
      fat dairy, could have a beneficial effect on blood pressure. We performed a dose
      response meta-analysis of prospective cohort studies on dairy intake and risk of
      hypertension in the general population. A systematic literature search for
      eligible studies was conducted until July 2011, using literature databases and
      hand search. Study-specific dose-response associations were computed according to
      the generalized least squares for trend estimation method, and linear and
      piecewise regression models were created. Random-effects models were performed
      with summarized dose-response data. We included 9 studies with a sample size of
      57 256, a total of 15 367 incident hypertension cases, and a follow-up time
      between 2 and 15 years. Total dairy (9 studies; range of intake, ~100-700 g/d),
      low-fat dairy (6 studies; ~100-500 g/d), and milk (7 studies; ~100-500 g/d) were
      inversely and linearly associated with a lower risk of hypertension. The pooled
      relative risks per 200 g/d were 0.97 (95% CI, 0.95-0.99) for total dairy, 0.96
      (95% CI, 0.93-0.99) for low-fat dairy, and 0.96 (95% CI, 0.94-0.98) for milk.
      High-fat dairy (6 studies), total fermented dairy (4 studies), yogurt (5
      studies), and cheese (8 studies) were not significantly associated with
      hypertension incidence (pooled relative risks of ~1). This meta-analysis of
      prospective cohort studies suggests that low-fat dairy and milk could contribute
      to the prevention of hypertension, which needs confirmation in randomized
      controlled trials.

PMID- 22987923
TI  - Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing
      a corin variant identified in blacks.
AB  - Blacks represent a high-risk population for salt-sensitive hypertension and heart
      disease, but the underlying mechanism remains unclear. Corin is a cardiac
      protease that regulates blood pressure by activating natriuretic peptides. A
      corin gene variant (T555I/Q568P) was identified in blacks with hypertension and
      cardiac hypertrophy. In this study, we tested the hypothesis that the corin
      variant contributes to the hypertensive and cardiac hypertrophic phenotype in
      vivo. Transgenic mice were generated to express wild-type (WT) or T555I/Q568P
      variant corin in the heart under the control of alpha-myosin heavy chain
      promoter. The mice were crossed into a corin knockout (KO) background to create
      KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the
      heart. Functional studies showed that KO/TgV mice had significantly higher levels
      of proatrial natriuretic peptide in the heart compared with that in control
      KO/TgWT mice, indicating that the corin variant was defective in processing
      natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to
      have hypertension that was sensitive to dietary salt loading. The mice also
      developed cardiac hypertrophy at 12 to 14 months of age when fed a normal salt
      diet or at a younger age when fed a high-salt diet. The phenotype of salt
      sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles
      the pathological findings in blacks who carry the corin variant. The results
      indicate that corin defects may represent an important mechanism in salt
      sensitive hypertension and cardiac hypertrophy in blacks.

PMID- 22987942
TI  - From chemotherapy to targeted treatment.
AB  - Today, melanoma is considered as a spectrum of melanocytic malignancies that can
      be characterized by clinical and molecular features, including targetable
      mutations in several kinases. The successful development of therapies, targeting
      mutated BRaF (v-raf murine sarcoma viral oncogene homolog B1) or c-KIT (v-kit
      Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog), has resulted in new
      treatment options including vemurafenib, imatinib and mitogen-activated protein
      kinase inhibitors. These molecules are selected if the respective mutation is
      present. after this first progress in the treatment of advanced melanoma, there
      is expectation that combinations of kinase inhibitor will additionally improve
      the overall survival rates and progression-free survival in advanced melanoma.

PMID- 22987943
TI  - Advances and perspectives in immunotherapy of melanoma.
AB  - Immunotherapy using unspecific modulators has a long tradition in the adjuvant
      treatment of stage II/III melanoma. Interferon has shown a consistent effect on
      relapse-free survival independent of interferon dosage and duration. The results
      of the american Joint Committee on Cancer (AJCC) Melanoma Staging Database
      analysis led to a strict inclusion of additional prognostic risk factors such as
      ulceration of the primary and microscopic lymph node involvement explored by the
      sentinel node biopsy in the revised 2009 AJCC classification. These factors are
      now being increasingly included as stratification factors into clinical trials
      and yield a new hypothesis that primarily patients with both characteristics
      benefit from adjuvant interferon treatment. In the metastatic situation,
      interleukin-2 is the only immunotherapeutic agent approved by the Food and Drug
      administration. In combination with interferon and/or with various
      chemotherapeutic agents, IL-2 is associated with substantial toxic effect and
      poor efficacy that does not improve overall survival (OS). Ipilimumab is a fully
      human, monoclonal antibody that blocks the cytotoxic T-lymphocyte antigen-4 and
      has recently been approved for metastatic melanoma based on two independent
      randomized phase III studies both demonstrating an improved OS rate after 1, 2,
      and 3 years compared with the control group. Based on this major step in treating
      metastatic melanoma, novel adjuvant strategies in stage III and combination
      therapies with targeted agents in stage IV are currently being explored.

PMID- 22987945
TI  - Optimal first-line treatment in ovarian cancer.
AB  - Treatment of ovarian cancer remains challenging despite the high complete
      response rate seen after maximal surgical debulking surgery and platinum
      combination chemotherapy. as most patients will relapse and eventually succumb to
      ovarian cancer, new strategies are urgently required to improve survival. a
      platinum-taxane combination has been the cornerstone of treatment for >15 years.
      Better use of these drugs is being explored through scheduling studies, and dose
      dense or intraperitoneal (IP) therapies. Further improvements in treatment will
      most likely come from the integration of optimal chemotherapy with one or more of
      the hundreds of molecular-targeted agents that could be active in ovarian cancer.
      The greatest experience has been with anti-angiogenic agents. Two large phase III
      trials in first-line ovarian cancer have demonstrated a positive effect of
      bevacizumab when administered concurrently with chemotherapy and then as a
      maintenance treatment. In this review, we discuss the existing treatments for
      ovarian cancer and highlight areas of recent progress.

PMID- 22987944
TI  - New insights into ovarian cancer pathology.
AB  - Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and
      also the most lethal gynecological malignancies. Based on histopathology and
      molecular genetic alterations, ovarian carcinomas are divided into five main
      types [high-grade serous (70%), endometrioid (10%), clear-cell (10%), mucinous
      (3%), and low-grade serous carcinomas (<5%)] that account for over 95% of cases.
      These types are essentially distinct diseases, as indicated by differences in
      epidemiological and genetic risk factors, precursor lesions, patterns of spread,
      and molecular events during oncogenesis, response to chemotherapy, and prognosis.
      For a successful specific treatment, reproducible histopathological diagnosis of
      the tumor cell type is critical. The five tumor types are morphologically diverse
      and resemble carcinomas of the uterus. Actually, recent investigations have
      demonstrated that a substantial number of cancers, traditionally thought to be
      primary ovarian tumors (particularly serous, endometrioid, and clear-cell
      carcinomas), originate in the fallopian tube and the endometrium and involve the
      ovary secondarily. This presentation summarizes recent advances in the molecular
      pathology which have greatly improved our understanding of the biology of ovarian
      carcinoma and are also relevant to patient management.

PMID- 22987947
TI  - How to approach patients in relapse.

PMID- 22987949
TI  - New insights into pancreatic cancer biology.
AB  - Pancreatic cancer remains a devastating disease. Over the last few years, there
      have been important advances in the molecular and biological understanding of
      pancreatic cancer. This included understanding of the genomic complexity of the
      disease, the role of pancreatic cancer stem cells, the relevance of the tumor
      microenvironment, and the unique metabolic adaptation of pancreas cancer cells to
      obtain nutrients under hypoxic environment. In this paper, we review the most
      salient developments in these few areas.

PMID- 22987950
TI  - Treatment of advanced pancreatic cancer.

PMID- 22987951
TI  - Treatment of locoregional disease: adjuvant versus neoadjuvant.
AB  - The efficacy of adjuvant therapy after the resection of pancreatic adenocarcinoma
      has been demonstrated by several randomized studies. Postoperative treatment
      applied either as chemotherapy alone or in combination with chemoradiotherapy is
      therefore considered a recommended standard in resectable pancreatic cancer (PC).
      Multiple arguments speak in favor of preoperative systemic therapy. Specifically,
      the conception of PC as a metastatic disease even at the early stage of apparent
      resectability supports the strategy of upfront systemic therapy. Unfortunately,
      randomized studies comparing neoadjuvant with adjuvant regimens have not been
      performed, and the superiority of one strategy over the other still has to be
      confirmed. Future clinical research may even combine neoadjuvant and adjuvant
      treatment. New avenues of individualized treatment may also be reached by the
      inclusion of molecular parameters of the tumor and pharmacogenomic profiles of
      the patient into decision making.

PMID- 22987952
TI  - The treatment of uterine sarcomas.
AB  - Uterine sarcomas are rare and comprise only 3% of all uterine cancers. Within the
      group of adult soft tissue sarcomas, they account for ~7% of new cases. They
      consist of several distinct histological subtypes like leiomyosarcoma,
      endometrial stromal tumors, undifferentiated sarcomas, pure heterologous
      sarcomas, and mixed epithelial and mesenchymal tumors. Standard treatment in
      localized disease is abdominal hysterectomy. Bilateral salpingo-oophorectomy and
      lymphadenectomy have no proven value in leiomyosarcomas and high-grade
      undifferentiated sarcomas. However, in endometrial stromal tumors, given the
      hormonal reponsiveness of most tumors, salpingo-oophorectomy is generally
      recommended. Carcinosarcomas are treated according to current recommendations for
      epithelial uterine cancers. In leiomyosarcomas, postoperative radiation does not
      improve both relapse-free and overall survival. adjuvant chemotherapy seems to
      improve survival in the context of uncontrolled phase II trials. However, it is
      currently not considered standard of care in the absence of data from randomized
      trials. In contrast, adjuvant chemotherapy does improve overall survival in
      carcinosarcomas and is therefore considered standard of care. Systemic therapy
      for advanced uterine leiomyosarcomas, undifferentiated uterine sarcomas, and
      heterologous sarcomas is generally following the recommendations for adult soft
      tissue sarcomas. Endometrial stromal sarcomas are usually hormonal receptor
      positive, which allows endocrine therapy in most cases.

PMID- 22987953
TI  - The treatment of desmoid tumors: a stepwise clinical approach.
AB  - Aggressive fibromatosis (AF) is a monoclonal proliferative disease but does not
      metastasize and does not dedifferentiate to a high-grade malignancy in case of
      recurrence. Biopsy is usually necessary to confirm the diagnosis. A hallmark is
      its apparent unpredictable clinical course producing a large heterogeneity even
      with an indistinguishable morphology. Additional studies of the molecular
      determinants of desmoid behavior are needed to guide selection of the various
      therapeutic modalities. During the last 10 years, the treatment of AF has evolved
      and the role of routine, aggressive first-line treatment (radiotherapy and
      surgery) is now debated. If a wait-and-see policy is used at initial
      presentation, it is observed that >50% of patients will have relatively indolent
      disease. Aggressive treatments that take their indications from retrospective
      studies should be re-evaluated in the light of new data. The objective of this
      article is to propose an algorithm that commences with more conservative
      approaches before treatments that have associated long-term morbidity, the more
      aggressive therapies being reserved only for those who really need it.

PMID- 22987955
TI  - Histology- and non-histology-driven therapy for treatment of soft tissue
      sarcomas.
AB  - Medical treatment of adult soft tissue sarcomas is more and more dictated by the
      histological subtype, in a family of rare cancers made up of dozens of these
      subsets. This applies to both cytotoxics and target therapies. In addition to
      doxorubicin and ifosfamide, therefore, there is evidence of efficacy of
      gemcitabine in leiomyosarcomas; trabectedin in leiomyosarcomas and liposarcomas,
      with an exceedingly high activity in myxoid liposarcoma; taxanes and gemcitabine
      in angiosarcoma. With regard to target therapies, imatinib is paradigmatically
      effective in the usually non-medically treated dermatofibrosarcoma. Then, in the
      face of a strong rationale, mammalian target of rapamycin (mTOR) inhibitors are
      active in a proportion of PEComas (perivascular epithelioid cell tumours) and
      crizotinib in ALK-rearranged inflammatory myofibroblastic tumours. Though the
      mechanism is less understood at the moment, pazopanib seems especially active in
      leiomyosarcoma and synovial sarcoma; sunitinib and cediranib in alveolar soft
      part sarcomas; sunitinib and bevacizumab-temozolomide in solitary fibrous
      tumours; sorafenib in angiosarcomas. Pazopanib was also proved to prolong
      progression-free survival in a trial including pre-treated patients suffering
      from all advanced adult soft tissue sarcomas excluding liposarcomas. all this
      highlights the current need for new methods to do clinical studies on rare
      cancers, amid highly specific though anecdotal proofs and less specific though
      statistically more powerful evidence.

PMID- 22987957
TI  - Treatment choice for locally advanced head and neck cancers on the basis of risk
      factors: biological risk factors.
AB  - Patients with locally advanced head and neck squamous cell carcinoma often
      experience relapse, the cause of poor survival statistics. Relapse occurs
      following the three main types of treatment, surgery with or without post
      operative (chemo)radiotherapy, or chemoradiation (containing cisplatin). Cancer
      relapse can result from (i) outgrowth of residual tumour cells, sometimes with a
      number too small to be detected by routine histopathology or (ii) development of
      another carcinoma in a field of pre-neoplastic cells that has remained after
      treatment of the primary carcinoma. At this moment, clinical staging is not
      enough to identify patients who will develop relapse and who need tailored
      treatment. This review describes the latest knowledge of mechanisms of cancer
      relapse, addresses the biomarkers of potential interest detectable in the tissue
      of the tumour or its surgical margins and discusses three biomarkers, human
      papillomavirus, TP53 and epidermal growth receptor in more detail. Once a marker
      panel has been established, treatment should be focussed on the patients at risk
      of relapse by improved tailoring of existing treatment modalities. Also, the
      implementation of more targeting therapies based on the characteristics of the
      discovered markers should lead to better survival rates.

PMID- 22987958
TI  - Locally advanced head and neck squamous cell cancer: treatment choice based on
      risk factors and optimizing drug prescription.
AB  - Despite the policy changes to decrease tobacco consumption and therapeutic
      advances in this disease, squamous cell carcinomas arising from the head and neck
      (HNSCC) continue to represent a common neoplasm and a leading cause of cancer
      related mortality in Europe and worldwide. although different approaches have
      been evaluated, no treatment has currently been shown to be superior to cisplatin
      (Platinol, Corden Pharma) based chemoradiation in locally advanced HNSCC. Based
      on retrospective subgroup analyses from multiple large clinical trials, human
      papillomavirus (HPV) status has been shown to be a validated prognostic factor in
      oropharyngeal tumors. Patients with HPV-related tumors, especially those who are
      non-smokers, have generally excellent outcome as their tumors are highly
      sensitive to both chemotherapy and radiation, whereas those with tobacco-related
      and HPV-negative tumors, who continue to represent substantial number of cases in
      Europe, have worse prognosis with tumors that are more resistant to treatment.
      The goal of treatment de-intensification in patients with favorable risk is to
      avoid long-term and late toxicity, but this must be achieved without compromise
      of treatment efficacy. For those with risk factors that portend a worse
      prognosis, the question remains whether addition to or modification of
      conventional treatment regimens would improve upon therapeutic index. Innovative
      clinical trial designs specifically tailored to these risk groups are urgently
      needed.

PMID- 22987959
TI  - Can sensitivity to cytotoxic chemotherapy be predicted by biomarkers?
AB  - Non-small-cell lung cancer is the leading cause of cancer-related death worldwide
      with poor outcomes, even when a curative treatment approach is feasible.
      Chemotherapy remains a useful option for the majority of patients with advanced
      or relapsed disease as well as having a substantial role in the adjuvant setting.
      Identifying predictive biomarkers would enable us to better select those patients
      more likely to benefit from chemotherapy while avoiding toxic effects in those
      patients not deriving benefit from chemotherapy. although the use of biomarkers
      to select chemotherapy is not the standard approach, several potential biomarkers
      have been identified and a few prospective trials are ongoing. We review here the
      most-studied biomarkers for chemotherapy.

PMID- 22987961
TI  - Epidermal growth factor receptor (EGFR) inhibitors and derived treatments.
AB  - Epidermal growth factor receptor inhibitors are used to treat advanced lung
      cancer patients for almost a decade. Current knowledge on their role in the first
      or subsequent lines of therapy serves as a model for other targeted therapies in
      development. Several molecular predictors of outcomes were successfully
      identified in preclinical and clinical studies. Evaluation of EGFR-activating
      mutations is currently used to define biologically distinct patient subsets with
      important consequences for prognosis and therapy. Ongoing translational and
      clinical research exploring EGFR inhibition in lung cancer focuses on better
      understanding of biology of EGFR-driven disease, efficacy of novel irreversible
      EGFR inhibitors and monoclonal antibodies, efficacy of combination strategies,
      and attempts to move EGFR inhibitors into therapy portfolio for early-stage
      disease.

PMID- 22987962
TI  - Going beyond EGFR.
AB  - a substantial proportion of non-small-cell lung cancer (NSCLC), and
      adenocarcinoma in particular, depends on a so-called 'driver mutation' for their
      malignant phenotype. This genetic alteration induces and sustains tumorigenesis,
      and targeting of its protein product can result in growth inhibition, tumor
      response and increased patient survival. NSCLC can thus be subdivided into
      clinically relevant molecular subsets. Mutations in EGFR best illustrate the
      therapeutic relevance of molecular classification. This article reviews the scope
      of presently known driving molecular alterations, including ROS1, BRAF, KRAS,
      HER2 and PIK3CA, with a special emphasis on aLK rearrangements, and outlines
      their potential therapeutic applications.

PMID- 22987963
TI  - The current state of breast cancer classification.
AB  - Breast cancer is a highly heterogeneous disease due to its diverse morphological
      features, the variable clinical outcome and the response to different therapeutic
      options. It is therefore necessary to devise a clinically meaningful
      classification of the disease, which has to be scientifically sound, clinically
      useful and widely reproducible. The established histopathological classification
      has a limited clinical utility, due to insufficient prognostic and predictive
      power. More recent classification schemes, based on the immunohistochemical
      characterization of breast cancer for the assessment of hormone receptor status,
      HER2 gene over-expression or amplification and the proliferative fraction or on
      gene expression profiles, correlate much better with the clinical outcome and may
      be used to inform the choice of the systemic therapy.

PMID- 22987965
TI  - Genomic analyses to select patients for adjuvant chemotherapy: trials and
      tribulations.
AB  - Despite improvements in adjuvant chemotherapy regimens in breast cancer,
      personalised use of specific cytotoxic regimens remains a clinical challenge.
      Defining the correct therapeutic strategy for individual patients with breast
      cancer based on the genomic and transcriptomic characteristics of the tumour and
      the patient remains an area of unmet clinical need. Despite the promise of
      microarray-based predictors of response to chemotherapy, clinical decisions are
      still guided by a limited constellation of biomarkers. In this review we will
      address current genomic and transcriptomic approaches to the stratification of
      adjuvant therapies in breast cancer, the reasons for the limited success in the
      incorporation of novel multi-gene predictors of response to chemotherapy in
      clinical practice and focus on new approaches that aim to understand the clonal
      evolution of the disease. The polygenic nature of drug resistance, and inter- and
      intra-tumour heterogeneity are considered as important research areas, given that
      they may constitute important challenges for the development of chemotherapy
      specific response predictors.

PMID- 22987966
TI  - Developments in Ki67 and other biomarkers for treatment decision making in breast
      cancer.
AB  - Estrogen receptor (ER) and HER2 are well established as predictive markers for
      treatment benefit, although methodological deficiencies can still affect their
      predictive accuracy. The shift towards earlier diagnosis poses a challenge in
      identifying those low-risk patients who may safely avoid adjuvant chemotherapy
      for early breast cancer. Therefore, recent research has focused on developing
      biomarkers to quantify residual risk on adjuvant endocrine therapy. For
      widespread adoption into clinical practice, these must be validated in well
      designed clinical trials and provide additional information to current standards
      using reproducible and cost-effective methodologies. Furthermore, evidence from
      preoperative studies indicates that on- or post-treatment biomarkers can be more
      predictive than at baseline. In particular, Ki67 has recently emerged as an
      intermediate marker of long-term outcome. The power of Ki67 to predict treatment
      benefit from endocrine therapy has facilitated the design of studies where Ki67
      is the primary end-point. This has also led to investigations into the predictive
      power of Ki67 to determine benefit from signal transduction inhibitors and
      chemotherapy in several recent and ongoing trials.

PMID- 22987968
TI  - Neoadjuvant treatment of breast cancer.
AB  - Neoadjuvant treatment of breast cancer has become established as the safe and
      often effective therapeutic approach of choice for larger primary and for locally
      advanced breast cancer. The neoadjuvant approach offers the advantages of
      downstaging the disease, potentially reducing the extent of surgery and in an era
      of individualization of therapy, testing the efficacy of therapy administered to
      patients. The preoperative setting is also an effective way to study the activity
      of novel agents or therapeutic combinations in vivo against human breast cancer.
      For new therapies, preoperative trials avoid the issue of adaptive resistance and
      pretreatments that can be problematic in the advanced disease setting. For
      evidence of a drug targeting the cancer in vivo, comparisons of endocrine
      therapy, chemotherapy agents and/or targeted agents can provide data on activity
      and efficacy with a much shorter time frame and many fewer patients than for
      adjuvant trials; effects seen in neoadjuvant trials may even reflect what is
      found in the adjuvant setting. Patient benefits from the neoadjuvant approach may
      be greatest for those who experience complete pathologically documented response
      (and the consequent survival benefits) and women for whom breast conservation,
      rather than mastectomy, becomes possible.

PMID- 22987969
TI  - Neoadjuvant treatment for HER-2-positive and triple-negative breast cancers.
AB  - Neoadjuvant therapy (NT) has become a valuable research tool for the
      incorporation of alternative cytotoxic agents, as well as new biological
      therapies, into anthracycline and taxane chemotherapy-based regimens. Her-2
      positive disease is predictive of higher pathological complete response (pCR) to
      neoadjuvant chemotherapy and trastuzumab. Benefits were also seen for the
      combination of trastuzumab with lapatinib or pertuzumab, suggesting that dual
      blockage of the HER-2 will probably emerge as the new standard. Triple-negative
      phenotype is also predictive of high pCR to NT, but the prognosis of patients
      whose tumours do not achieve a pCR after neoadjuvant chemotherapy with
      anthracyclines and taxanes is dismal. Currently, it is recommended to use the
      same chemotherapy regimens as in non-triple-negative disease. The suggested
      benefit of neoadjuvant platinum, mainly in BRCA1-related cancers, needs to be
      confirmed in large randomized trials. Bevacizumab combined with neoadjuvant
      chemotherapy yields increased pCR compared with non-bevacizumab treatment, in
      large randomized data recently published. One study suggested higher benefit in
      triple-negative tumours. Long-term follow-up of these trials is needed to
      understand the role of bevacizumab treatment in BC and its important to find
      predictive biomarkers of response to this drug.

PMID- 22987970
TI  - Neoadjuvant therapy for ER-positive breast cancers.
AB  - ER-positive, HER-2-negative operable breast cancer represents a heterogeneous
      group of tumors. Tumor subtypes associated with different responses to
      neoadjuvant therapies can be identified through the evaluation of pathological
      features that include grade, the degree of expression of estrogen (ER) and
      progesterone (PgR) receptors and markers of cell proliferation such as Ki67
      labeling index. For patients with a high proliferative index and/or a high grade
      who have a higher likelihood for a pathologic complete response, the selection of
      neoadjuvant chemotherapy should follow the same algorithm utilized for
      postoperative adjuvant treatments. In particular, both anthracyclines and taxanes
      should be evaluated for the chemotherapy regimen. Neoadjuvant endocrine therapy
      should be considered in place of cytotoxic neoadjuvant therapy for postmenopausal
      patients with tumors with low grade or proliferation and high ER and PgR
      expression. If given, such treatment should be continued for a minimum of 4-8
      months. Selected patients with special types of breast cancer (e.g. pure tubular,
      cribriform and mucinous tumors) have a limited expected benefit from preoperative
      therapy and might receive adjuvant endocrine therapy alone. Tailored neoadjuvant
      treatments should be considered in patients with ER-positive tumors. Issues
      focusing on safety, quality of life and patient preference should be routinely
      discussed.

PMID- 22987971
TI  - Can molecular markers help with decision making?

PMID- 22987972
TI  - Non-metastatic CRPC and asymptomatic metastatic CRPC: which treatment for which
      patient?
AB  - The introduction of early PSa-based diagnosis has profoundly impacted the
      epidemiology of castration-resistant prostate cancer (CRPC). Many patients enter
      the disease at an early stage when the only sign of resistance to androgen
      deprivation therapy (ADT) is a progressive elevation of prostate-specific antigen
      (PSA). This created a very heterogeneous population of non-metastatic (M0) CRPC.
      PSa kinetics is the most powerful indicator of aggressiveness in that population
      and can be used to trigger imaging investigation and enrollment in clinical
      trials. Several registered and near to come treatments have not been tested in
      that population but in men with more advanced metastatic and often symptomatic
      disease. Several agents have been investigated to delay the onset of the first
      bone metastasis but only one, denosumab, has reached its end-point. Because CRPC
      remains largely driven by the androgen receptor (AR), physicians have relied on
      second-line hormonal manipulations to delay the progression of the disease,
      including first generation antiandrogens, adrenal synthesis inhibitors, steroids
      and estrogens. The data however are mostly limited to phase II trials.

PMID- 22987973
TI  - Novel hormonal therapy for castration-resistant prostate cancer.

PMID- 22987974
TI  - Novel and bone-targeted agents for CRPC.
AB  - Clearly, no neoplasm other than prostate cancer has benefited from so many
      breakthroughs since the beginning of this decade: the past two years can be
      considered exceptional due to the number of emerging agents against castration
      resistant prostate cancer (CRPC), which have demonstrated positive outcomes in
      phase III trials. Until 2010, docetaxel (Taxotere) was the only agent capable of
      improving survival in patients with metastatic CRPC. Since then, positive results
      from phase III trials have been reported for sipuleucel-T, cabazitaxel,
      denosumab, abiraterone, radium-223, and enzalutamide, while other promising
      agents including notably orteronel, ipilimumab and cabozantinib are currently
      under study. Taken together, the incorporation of these agents in the routine
      management of patients with CRPC is likely to expand their median life
      expectancy, which was only ~1 year until the early 2000, to >30 months in the
      near future. The availability of these agents will lead to new challenges and
      questions, such as: Can our societies afford the costs? Should we use these
      agents sequentially or in combination with an incremental benefit? Can we
      personalise treatment based on the biology of the individual's disease? How will
      we develop new active compounds in the context where a half dozen approved agents
      may confound their potential overall survival effect?

PMID- 22987975
TI  - Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to
      molecular profiling.
AB  - Carcinoma of unknown primary (CUP) remains a common and challenging clinical
      problem. The aim of diagnostic work-up in CUP is to classify as specifically as
      possible the cancer affecting the patient, according to the broad tumour type,
      subtype and, where possible, site of origin. This classification currently best
      predicts patient outcome and guides optimal treatment. a stepwise approach to
      diagnostic work-up is described. although pathology is based on morphology, the
      assessment of tissue-specific genes through immunohistochemistry (IHC)
      substantially helps tumour classification at each diagnostic step. For IHC in
      CUP, recent improvements include more standardised approaches and marker panels
      plus new markers. Tissue-specific genes are also being used in CUP work-up
      through molecular profiling. Large-scale profiles of hundreds of tumours of
      different types have been generated, compared and used to generate diagnostic
      algorithms. Commercial tests for CUP classification have been developed at the
      mRNa and microRNA and (miRNA) levels and validated in metastatic tumours and
      CUPs. While currently optimal pathology and IHC remain the 'gold standard' for
      CUP diagnostic work-up, and full clinical correlation is vital, the molecular
      tests appear to perform well: in the main diagnostic challenge of
      undifferentiated or poorly differentiated tumours, molecular profiling performs
      as well as or better than IHC.

PMID- 22987976
TI  - CUP: looking for a missing primary site and its biology.

PMID- 22987977
TI  - Personalized surgical therapy.
AB  - Gliomas are more or less diffuse tumours with the ability to infiltrate
      surrounding functional brain tissue. Thus, curative surgical treatment generally
      cannot be achieved. Despite these limitations, open tumour resection represents
      one of the mainstays in glioma treatment settings. Beyond tissue sampling for
      accurate histological and molecular genetic evaluation, decompressive effects in
      the case of space occupying tumours and oncologically relevant cytoreductive
      effects of microsurgery have been reported in selected patients with glioma of
      different grades. This paper provides practical considerations in order to
      integrate the concept of a personalized surgical therapy into the prognostic
      network of low- and high-grade gliomas, covering both microsurgery and
      stereotactic biopsy techniques.

PMID- 22987978
TI  - Optimal therapeutic management of patients with distinct clinicopathological
      cancer of unknown primary subsets.
AB  - Cancer of unknown primary sites (CUP) is a compilation of various malignant
      entities--the majority of which behave aggressively and carry poor prognosis. CUP
      is classified into two different clinicopathological groups: the unfavourable
      (poor-prognosis) and the favourable (good-prognosis) group. Patients with
      favourable subsets are treated relevant to the hidden primary tumour chemotherapy
      regimens and/or radiotherapy. These patients exhibit better responses and
      prolonged survival. On the other hand, patients of unfavourable subsets are
      treated with various chemotherapy combinations of platinum- or taxane-containing
      regimens. Unfortunately, responses and overall survival in this group of CUP
      patient are not very promising. Several independent prognostic factors have been
      associated with survival of CUP patients. Since CUP is not an unknown disease,
      emerging therapeutic innovations are warranted.

PMID- 22987979
TI  - Emerging topics in anaemia and cancer.
AB  - Erythropoiesis-stimulating agents (ESAs) increase red blood cell (RBC) production
      by activating the erythropoietin receptor on erythrocytic progenitor cells. ESAs
      are approved in the United States and Europe for treating anaemia in cancer
      patients receiving chemotherapy. ESA safety issues include thromboembolic events
      and there have been concerns about disease progression and/or mortality in cancer
      patients. This educational supplement paper is based on two recently published
      papers. We review both clinical trial data on ESAs and disease progression and
      preclinical data on how ESAs could affect tumour growth. We conclude that ESAs
      may have little effect on disease progression in chemotherapy patients, and
      preclinical data indicate a direct or indirect effect of ESAs on tumour growth is
      not strongly supported. We also summarise the mechanisms and clinical
      consequences of iron deficiency and anaemia in cancer patients. Randomised
      clinical trials have shown superior efficacy of i.v. iron over oral or no iron in
      reducing blood transfusions, increasing haemoglobin, and improving quality of
      life in ESA-treated anaemic advanced cancer patients. Furthermore, i.v. iron
      without additional ESA should be evaluated as potential treatment in patients
      with chemotherapy-induced anaemia. at recommended doses, i.v. iron is well
      tolerated, particularly compared with oral iron, but caution should be used in
      some specific situations.

PMID- 22987980
TI  - Pain management.
AB  - Despite published guidelines and educational programs on the assessment and
      treatment of cancer-related pain, in any stage of oncological disease, unrelieved
      pain continues to be a substantial worldwide public health concern either in
      patients with solid and haematological malignancies. The proper and regular self
      reporting assessment of pain is the first step for an effective and
      individualized treatment. Opioids are the mainstay of analgesic therapy and can
      be associated with non-opioids drugs such as paracetamol or non-steroidal anti
      inflammatory drugs and to adjuvant drugs (for neuropathic pain and symptom
      control). The role and the utility of weak opioids (i.e. codeine, dihydrocodeine,
      tramadol) are a controversy point. Morphine has been placed by World Health
      Organization on its Essential Drug List. In the comparative study with other
      strong opioids (hydromorphone, oxycodone), there is no evidence to show
      superiority or inferiority with morphine as the first choice opioid. Oral
      methadone is a useful and safe alternative to morphine. Methadone presents the
      potential to control pain difficult to manage with other opioids. although the
      oral route of opioid administration is considered the one of choice, intravenous,
      subcutaneous, rectal, transdermal, sublingual, intranasal, and spinal routes must
      be used in particular situation. Transdermal opioids such as fentanyl and
      buprenorphine are best reserved for patients whose opioid requirements are
      stable. Switching from one opioid to another can improve analgesia and
      tolerability.

PMID- 22987981
TI  - Psychological aspects of depression in cancer patients: an update.

PMID- 22987982
TI  - How to select amongst available options for the treatment of advanced RCC?
AB  - The treatment of renal cell carcinoma has dramatically changed in the past 6
      years with the approval of seven new drugs since 2006. although treatment
      algorithms have been reported and updated every year since 2006, the choice of
      targeted therapy is not always easy. Selecting a targeted agent in metastatic
      renal cell carcinoma (mRCC) should take into account various parameters,
      including the status of the disease, the histology, the status of the patient and
      finally the availability of the drugs in each country. In addition, in front of
      every patient, the physician will need to raise important questions such as
      whether the patient should be treated, should receive surgery, and also what is
      his prognostic group. The different options are described in this manuscript.

PMID- 22987983
TI  - Prevention and handling of acute allergic and infusion reactions in oncology.
AB  - Drug hypersensitivity reactions (HSR) are adverse events resembling allergy which
      occur at therapeutic doses. Both anticancer chemotherapeutics and monoclonal
      antibodies have the potential for acute HSR. all infusion reactions involve the
      immune system; however, some (anaphylactic) are allergic in nature and usually
      are mediated by immunoglobulin E (IgE), whereas others (anaphylactoid) are not
      true allergic reactions and are not mediated by IgE. although HSR can be allergic
      or nonallergic, the clinical manifestations are the same and require prompt,
      accurate assessment and management to avoid severe adverse events, including
      fatality. Monoclonal antibodies have a unique side-effect profile that includes
      the potential for nonallergic HSR caused by cytokine release. Chemotherapeutic
      agents with the highest potential for acute HSR include the platinum salts,
      taxanes, procarbazine, asparaginase and the epipodophyllotoxins. From all
      anticancer agents, rituximab causes the majority of HSR (27%), followed by
      paclitaxel (10%). The most frequent symptoms in patients experiencing acute HSR
      include chest pain, dyspnea, wheezing and exanthema for the taxanes, dyspnea and
      exanthema for platinum salts, chills and rigor for antibodies. Patients with mild
      to-moderate acute HSR can be rechallenged following intensified prophylaxis, but
      rechallenge is usually not recommended following severe HSR.

PMID- 22987985
TI  - Multikinase inhibitors in thyroid cancer.

PMID- 22987984
TI  - Screening and early detection of lung cancer.
AB  - The greatest news of the past year in this field was the first large-scale early
      detection trial that could prove a 20% reduction in lung cancer-related mortality
      by screening high-risk individuals with low-dose computed tomography (LDCT).
      Several expert groups and medical societies have assessed the data and concluded
      that LDCT screening for lung cancer is, however, not ready for large-scale
      population-based implementation. Too many open questions remain, such as
      definition of the at-risk population, timing and intervals of screening, optimal
      method of acquisition and interpretation of the images, how to handle (false)
      positive findings, and especially cost-effectiveness in relation to other lung
      cancer prevention strategies, mainly smoking cessation. Further analyses and
      several ongoing European trials are eagerly awaited. Much hope also resides in
      the use of biomarkers, as their use in, e.g., blood or exhaled air may provide
      more easy-to-use tests to better stratify high-risk populations for screening
      studies. While exciting research is ongoing in this domain--e.g. with microRNAs-
      none of the tests has yet reached sufficient validation for clinical use. Early
      central lung cancers are more difficult to visualise by CT. For these patients,
      standard bronchoscopy, complemented by autofluoresence endoscopy, has been
      studied in different screening and follow-up settings.

PMID- 22987986
TI  - Decision making and management of gliomas: practical considerations.
AB  - Over the last decade, diagnostic options and introduction of novel treatments
      have expanded the armamentarium in the management of malignant glioma. Combined
      chemoradiotherapy has become the standard of care in glioblastoma up to the age
      of 70 years, while treatment in elderly patients or with lower grade glioma is
      less well defined. Molecular markers define different disease subtypes and allow
      for adapted treatment selection. This review focuses on simple questions arising
      in the daily management of patients.

PMID- 22987988
TI  - Issues in the adjuvant treatment of common tumors (with a focus on breast cancer)
      in older adults (age >70).
AB  - Establishing an indication for adjuvant chemotherapy in older cancer patients
      represents a major challenge. after surgery, older cancer patients can also have
      a significant risk of relapse and cancer death (even reported to be higher than
      in younger patients), but this is counterbalanced by the fact that the chance of
      dying from a noncancer cause is also much higher. a careful geriatric evaluation
      including assessment of comorbidity can provide some insight into the life
      expectancy and expected benefit from adjuvant chemotherapy for individual
      patients. age-related physiological changes can decrease tolerance of classical
      chemotherapy regimens, indicating the need for close monitoring and preventive
      measures.

PMID- 22987987
TI  - How to select among available options for the treatment of multiple myeloma.
AB  - The introduction of novel agents (thalidomide, bortezomib and lenalidomide) in
      the frontline therapy of multiple myeloma has markedly improved the outcome both
      in younger patients who are candidates for high-dose therapy plus autologous stem
      cell transplantation (HDT/ASCT) and in elderly patients. In the HDT/ASCT
      paradigm, novel agents may be used as induction therapy or after HDT/ASCT as
      consolidation and/or maintenance therapy. It is now possible to achieve up to 70%
      complete plus very good partial remission after HDT/ASCT and 70% 3-year
      progression-free survival (PFS). However long-term non-intensive therapy may also
      yield high response rates and prolonged PFS. Randomized trials comparing these
      two strategies are underway. In elderly patients, six randomized studies show the
      benefit of adding thalidomide to melphalan-prednisone (MP). a large randomized
      trial has also shown that the combination of bortezomib-MP is superior to MP for
      all parameters measuring the response and outcome. Finally, the role of
      maintenance is currently evaluated and a randomized trial shows that low-dose
      lenalidomide maintenance prolongs PFS.

PMID- 22987989
TI  - Surveillance or adjuvant treatments in stage 1 testis germ-cell tumours.
AB  - All patients with stage 1 testicular germ-cell tumours (TGCT) can expect to be
      permanently cured with currently available management approaches. Orchidectomy
      alone cures 80% of pure seminomas and 70%-75% of nonseminomatous and combined
      seminoma plus nonseminomatous germ-cell tumours of the testis (NSGCTT). Currently
      there are well-validated criteria for estimating recurrence risk in NSGCTT. The
      presence of vascular invasion (VI+) in the testicular primary identifies a group
      with a recurrence risk approaching 50%. In VI-cases, the risk is <=20%. Adjuvant
      chemotherapy with two cycles of bleomycin, etoposide, and cisplatin (BEP) is
      increasingly recommended in VI+ cases, and when offered is selected in place of
      surveillance by many VI- patients. In seminomatous germ-cell testicular tumours
      (SGCTT), there are no validated criteria for estimating recurrence risk. Concerns
      about second cancers complicating adjuvant radiotherapy are reducing its
      popularity and the absence of tumour markers, the need for frequent scans, long
      follow-up and evidence of poor compliance argue against surveillance. Single-dose
      carboplatin is well tolerated, cheap, reduces recurrence rates to <5% and also
      the risk of second primary TGCT. There remain concerns about long-term toxicity
      although evidence is accumulating to allay these. This article discusses the
      relevant issues affecting decision-making and choice in these intriguing, curable
      cancers.

PMID- 22987990
TI  - When to order a biopsy to characterise a metastatic relapse in breast cancer.
AB  - Today, the diagnosis of metastatic breast cancer is usually based on radiological
      findings, and therapeutic decisions are made by considering the pathological
      characteristics and predictive markers of the primary tumour. Accumulating
      evidence suggests that tumour characteristics, including estrogen receptor (ER)
      and human epidermal growth factor receptor 2 (HER2), are unstable through tumour
      progression. Several retrospective studies and, recently, two prospective studies
      have investigated the discrepancies in receptor status between primary tumours
      and the corresponding metastases in a total of 1773 patients (for ER) and 2845
      patients (for HER2). Changes in ER and HER2 status in these studies range from
      14.5% to 40% and from 0% to 37.5%, respectively. In the two prospective studies,
      a different diagnosis, usually non-malignant, was obtained in 3% and 9% of the
      cases, and the biopsy led to a treatment modification in about one out of seven
      patients. Here, we review and discuss the currently available data and provide
      our recommendations on when a metastatic biopsy should be obtained.

PMID- 22987991
TI  - Advances in surgery.
AB  - In the last decade, technological advances, new staging tools, better
      understanding the role of surgery within multimodal treatment concepts in
      advanced stages and progress in the functional assessment of surgical candidates
      improved the quality of surgery in the management of patients with lung cancer.
      Lung resection with video-assisted thoracoscopic access gained wide acceptance,
      the indication for lobectomy or sublobar resection in early stages was applied
      based on new data and selection for multimodal treatment in stage III is better
      understood based on the data. a major impact on the outcome of patients with lung
      cancer has the treatment in specialized high-volume centers.

PMID- 22987992
TI  - Developments in early-stage NSCLC: advances in radiotherapy.
AB  - An increase in the number of predominantly elderly patients with early-stage non
      small-cell lung cancer is anticipated in many Western populations. Patients often
      have major co-morbidities and are at increased risk for surgical morbidity and
      mortality. In the past decade, the use of stereotactic ablative radiotherapy
      (SABR) has achieved excellent results, with only mild toxicity in such vulnerable
      patient groups, leading to SABR becoming accepted as a standard of care for unfit
      patients in several countries. The planning and delivery of SABR has rapidly
      improved in recent years, particularly with the use of 'on-board' imaging at
      treatment units, and shortened treatment delivery times. Increasingly, more
      central tumors are being treated using lower doses per fraction (so-called risk
      adapted schemes). It is also becoming clear that long-term follow-up should take
      place at specialist centers in order to distinguish the evolving fibrosis that is
      frequently observed from the relatively infrequent local recurrences. Given the
      high local control rates and limited toxicity, increasing attention is being paid
      to the use of SABR in the subgroup of so-called borderline operable patients, and
      clinical trials comparing surgery and SABR in these patients are ongoing.

PMID- 22987993
TI  - Developments in the treatment of early NSCLC: when to use chemotherapy.
AB  - approximately 30% of lung carcinomas are resected and these cases are candidates
      for adjuvant treatments. The PORT meta-analysis reported in 1999 that
      postoperative radiotherapy had a detrimental effect for pathological N0 and N1
      patients, and a debatable effect for N2 patients. Following the results of the
      1995 meta-analysis on the role of chemotherapy (CT) in non-small-cell lung cancer
      (NSCLC), many randomized, controlled trials were launched to evaluate the effect
      of adjuvant cisplatin-based CT after the complete resection of NSCLC. The Lung
      adjuvant Ciplatin Evaluation pooled analysis included a total of 4584 patients
      recruited in five recent cisplatin-based adjuvant trials. It confirmed that
      adjuvant CT was associated with an absolute 5-year survival benefit of 5.3% (P =
      0.0043). In addition, it showed that adjuvant cisplatin-based CT is detrimental
      in cases of stage Ia resected NSCLC; it also suggested that the combination of
      vinorelbine and cisplatin was of more benefit than older two and three drug
      combinations. The individual data-based meta-analysis was also updated with a
      total of over 10 000 patients. It confirmed the substantial effect of
      postoperative CT, with or without postoperative radiotherapy, with a substantial
      overall benefit of 4% at 5 years. Recent results of biological programs suggest
      that evaluating the expression of various tumor markers, including excision
      repair cross-complementation group 1, may allow the identification of patients
      most likely to benefit from CT. If these results are confirmed, tailored therapy
      might be the next step forward for resected NSCLC.

PMID- 22987994
TI  - What can molecular pathology offer for optimal decision making?
AB  - In recent years, colorectal cancer (CRC), once a uniform disease with well
      understood carcinogenesis, has been divided into at least five different
      subgroups with distinct precursor lesions, pathways of carcinogenesis,
      morphological, and molecular characteristics. Moreover, new therapeutic concepts
      with 'targeted' substances have added to the complexity of the management of CRC
      patients. The clinical value of biomarkers in advanced CRC is indisputable ever
      since activating mutations of the KRAS oncogene have been shown to predict
      resistance to anti-epidermal growth factor receptor antibodies. Prognostic
      biomarkers predicting patient outcomes and predictive biomarkers forecasting
      response to a certain therapy may help us to improve therapeutic agent selection
      and patient management with the ultimate goal of maximizing the benefit of
      treatment and minimizing toxicity. Biomarkers with known implications in advanced
      CRC will be discussed in this paper.

PMID- 22987996
TI  - Current stages of adjuvant treatment of colon cancer.

PMID- 22987997
TI  - Conceptual approaches to metastatic disease.

PMID- 22987998
TI  - New insights into the diagnosis of lymphomas.
AB  - The current diagnosis of lymphoid neoplasias is based on the criteria of the
      World Health Organization (WHO) classification. This framework is built on two
      major principles: the stratification of neoplasms according to their derivation
      from precursor or mature cells and the definition of clinically relevant
      nonoverlapping diseases. The diagnosis is established by integrating the
      clinical, morphological, phenotypic, genetic and molecular characteristics of the
      tumors. This approach is reproducible, clinically relevant and scientifically
      sound. The elucidation of the human genome a decade ago and the development of
      high-throughput technologies have opened the possibility to search for
      comprehensive views of the genomic alterations of the tumors that are starting to
      influence our current approach to diagnosis. The new generation of sequencing
      technologies and their systematic application to human cancer and in particular
      to lymphoid neoplasms are revealing a landscape of somatic mutations of
      unprecedented complexity. These studies have already provided a number of
      important findings with functional and clinical implications. The translation of
      all this knowledge into the clinic is challenging and offers relevant
      perspectives.

PMID- 22988000
TI  - New agents for the treatment of lymphoma.
AB  - Despite improvements in the diagnosis and management of lymphomas, many patients
      remain incurable with available treatments. advances in preclinical research and
      a better understanding of the molecular biology of lymphomas have allowed the
      development of a high number of therapeutic agents with innovative mechanisms of
      action. Many of these new agents have shown activity in patients not responding
      to standard treatments and there is optimism that their incorporation into the
      standard of care can result in improved treatment outcomes. Here we review new
      monoclonal antibodies and small molecules that have recently entered clinical
      evaluation for patients with lymphomas.

PMID- 22987999
TI  - The role of FDG-PET and bone marrow examination in lymphoma staging.
AB  - The introduction of positron emission tomography using [F-18]fluorodeoxyglucose
      (FDG-PET) has had a substantial impact on the management of patients with
      lymphoma. Increasing numbers of patients are having an FDG-PET study as part of
      their initial staging, despite FDG-PET cannot be considered yet a standard
      procedure for staging in many types of lymphoma. FDG-PET has demonstrated its
      superiority over conventional imaging to identify nodal and extra-nodal sites of
      disease and provides complementary information to that obtained with bone marrow
      biopsy. This can result in disparities in the staging and prognostication of
      patients based on the procedures used to assess the extension of the disease. The
      difficulty lies in how to use the information provided by FDG-PET to communicate
      effectively when using staging classifications and prognostic indices that were
      designed following conventional imaging.

PMID- 22988001
TI  - Capillary electrophoresis of clenbuterol enantiomers and NMR investigation of the
      clenbuterol/carboxymethyl-beta-cyclodextrin complex.
AB  - A capillary electrophoretic method has been established for the separation of the
      enantiomers of clenbuterol. The effects of pH value, composition of the
      background electrolyte, concentration of carboxymethyl-beta-cyclodextrin (CM-beta
      CD), capillary temperature and running voltage have been investigated. The two
      enantiomers were separated in an uncoated capillary with phosphate buffer (50
      mmol/L, pH 3.5) containing 10 mmol/L CM-beta-CD. The capillary temperature was at
      15 degrees C and applied voltage was at 20 kV. The inclusion complex of CM-beta
      CD and clenbuterol was synthesized and characterized by two-dimensional rotating
      frame spectroscopy (2D ROESY). Based on the 2D ROESY analysis, an inclusion
      structure of the clenbuterol/CM-beta-CD complex was proposed, in which
      clenbuterol penetrated CM-beta-CD in a tilted manner due to the interaction of
      intermolecular hydrogen bonds between clenbuterol and CM-beta-CD.

PMID- 22988002
TI  - Development and validation of a stability-indicating RP-HPLC method for the
      simultaneous estimation of process related impurities and degradation products of
      rasagiline mesylate in pharmaceutical formulation.
AB  - A sensitive, stability-indicating gradient reverse phase high-performance liquid
      chromatography-ultraviolet method has been developed for the quantitative
      determination of process-related impurities and forced degradation products of
      rasagiline mesylate in pharmaceutical formulation. Efficient chromatographic
      separation was achieved on an ACE C8, 150 * 4.6 mm, 3 um column with mobile phase
      containing a gradient mixture of solvents A and B. The flow rate of the mobile
      phase was 0.8 mL/min with column temperature of 30 degrees C and detection
      wavelength at 210 nm. Rasagiline was subjected to the stress conditions of
      oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Rasagiline
      was found to degrade significantly in acid and thermal stress conditions. The
      degradation products were well resolved from rasagiline and its impurities. The
      peak purity test results confirmed that the rasagiline peak was homogenous and
      pure in all stress samples and the mass balance was found to be more than 97%,
      thus proving the stability-indicating power of the method. The developed method
      was validated according to the guidelines of the International Conference on
      Harmonization with respect to specificity, linearity, limits of detection and
      quantification, accuracy, precision and robustness.

PMID- 22988003
TI  - A rapid determination of patulin using capillary zone electrophoresis and its
      application to analysis of apple juices.
AB  - This study describes a capillary zone electrophoretic method for the
      determination of patulin. An optimum run buffer was found to be 25 mM of sodium
      tetraborate and 10% acetonitrile (v/v) at pH 10. Optimum conditions were
      determined to be: an applied voltage of 25 kV (normal polarity), temperature of
      25 degrees C and injection time of 10 s at 50 mbar; the signals of patulin and
      phenobarbital as internal standard were detected at 276 nm. The method was highly
      reproducible, with relative standard deviations of 0.02-0.85 for intra-day and
      0.04-0.42 for inter-day for standard patulin. Acceptable linearity [y = 0.0020C
      (MUg/L) - 0.0680 (r = 0.9999)] was obtained over a concentration range of 0.25 to
      4.99 ug/mL of patulin. The limits of detection and quantification were calculated
      to be 5.9 * 10(-3) and 1.79 * 10(-2) ug/mL, respectively. Recovery was 68.0%. The
      proposed method was applied to 21 apple juice samples purchased from different
      Turkish markets, and two were found to contain higher than the limits of the
      European Union Directive for patulin.

PMID- 22988004
TI  - Editorial on "Behavioral and emotional symptoms and primary headaches in
      children: a population-based study" by Arruda and Bigal.

PMID- 22988005
TI  - Behavioral and emotional symptoms and primary headaches in children: a population
      based study.
AB  - OBJECTIVE: To investigate behavioral and emotional symptoms in a community-based
      sample of children as a function of headache status and of headache frequency.
      METHODS: Our sample consisted of 1,856 children (5-11 years). Primary headaches
      were assessed using a validated headache questionnaire. Emotional symptoms were
      assessed by the Child Behavior Checklist (CBCL). CBCL scores were modeled as a
      function of headache status after adjustments for demographics and headache
      frequency. RESULTS: Relative to controls, children with migraine were
      significantly more likely to have abnormalities in the following CBCL domains:
      somatic, anxiety-depressive, social, attention, internalizing and total score.
      Children with tension-type headache (TTH) were significantly different from
      controls in the same domains but at a lower rate than migraine. In children with
      migraine, impairments significantly varied as a function of headache frequency,
      race, and income. In children with TTH, gender, age, and headache frequency were
      significantly associated with abnormal scores. CONCLUSIONS: Migraine and TTH are
      significantly associated with behavioral symptoms in several domains, and
      headache frequency affects the association. Internalizing symptoms are common in
      children with headaches, while externalizing symptoms (e.g. rule-breaking and
      aggressivity) are not significantly more common than in controls.

PMID- 22988006
TI  - Hemicranial pain in bilateral internal carotid artery dissection.

PMID- 22988007
TI  - Mental health issues in adolescents and young adults with type 1 diabetes:
      prevalence and impact on glycemic control.
AB  - Mental health comorbidities can negatively affect disease management in
      adolescents with chronic illnesses. This study sought to determine the prevalence
      and impact of mental health issues in a population of adolescents and young
      adults with type 1 diabetes. A cross-sectional study of 150 patients aged 11 to
      25 years with type 1 diabetes from an urban, academic diabetes center was
      conducted. Participants completed 3 validated mental health disorder screening
      instruments: Beck's Depression Inventory, the Screen for Child Anxiety Related
      Emotional Disorders-41 anxiety screen, and the Eating Disorder Screen for Primary
      Care. More than a third screened positive: 11.3% for depression, 21.3% for
      anxiety, and 20.7% for disordered eating (14.7% had >=2 positive screens).
      Patients with a positive screen had twice the odds of having poor glycemic
      control as those without, as measured by HgbA1c. This study supports screening
      for mental health issues in adolescents and young adults with type 1 diabetes.

PMID- 22988008
TI  - Reduction in the number of animals and the evaluation period for the positive
      control group in Tg.rasH2 short-term carcinogenicity studies.
AB  - The lack of a clear guidance on the adequate number of animals used for positive
      controls in the short-term (26-weeks) transgenic mouse carcinogenicity studies
      has resulted in the use of high number of animals. In our earlier Tg.rasH2
      studies, 25 mice/sex were used in the urethane-positive control dose groups that
      were sacrificed by 18 weeks. Based on a robust response, several of our protocols
      for Tg.rasH2 studies with 15 mice/sex and terminal sacrifice at 17 +/- 1 weeks
      were submitted and accepted by the Carcinogenicity Assessment Committee of the US
      Food and Drug Administration since we demonstrated close to 100% response for the
      development of lung and splenic tumors (target organs) in 500 mice/sex. These 500
      mice/sex included 17 groups of 25 mice/sex and 5 groups of 15 mice/sex.  The
      objective of this investigation was to determine whether the number of animals
      can be further reduced along with the shortened duration of exposure to urethane.
      Accordingly, 10 Tg.rasH2 mice/sex/group were administered a total of 3
      intraperitoneal (IP) injections of urethane (1000 mg/kg per day) on study days 1,
      3, and 5, and the presence of tumors in the lungs and spleen was evaluated after
      8, 10, 12, 14, or 16 weeks. Our results demonstrate that 100% of the mice at 8
      weeks had developed lung tumors, whereas close to 100% of the mice at 14 weeks
      had developed splenic tumors. Based on the development of lung tumors alone in
      100% of the mice, we recommend that 10 mice/sex are sufficient and that these
      mice can also be sacrificed as early as 10 +/- 1 weeks following the
      administration of urethane.

PMID- 22988009
TI  - Short- and long-term outcomes of coronary stenting in women versus men: results
      from the National Cardiovascular Data Registry Centers for Medicare & Medicaid
      services cohort.
AB  - BACKGROUND: Conflicting evidence exists on sex-based outcomes after coronary
      stenting. METHODS AND RESULTS: Data on 426 996 patients >=65 years old (42.3%
      women) from the National Cardiovascular Data Registry CathPCI Registry (2004
      2008) were linked to Medicare inpatient claims to compare in-hospital outcomes by
      sex and long-term outcomes by sex and stent type. In-hospital complications were
      more frequent in women than in men: death (3869 [2.2%] versus 3737 [1.6%];
      adjusted odds ratio, 1.41; 95% confidence interval [CI], 1.33-1.49), myocardial
      infarction (2365 [1.3%] versus 2858 [1.2%]; odds ratio, 1.19; 95% CI, 1.11-1.27),
      bleeding (7860 [4.4%] versus 5627 [2.3%]; odds ratio, 1.86; 95% CI, 1.79-1.93),
      and vascular complications (2381 [1.3%] versus 1648 [0.7%]; odds ratio, 1.85; 95%
      CI, 1.73-1.99). At 20.4 months, women had a lower adjusted risk of death (hazard
      ratio [HR], 0.92; 95% CI, 0.90-0.94) but similar rates of myocardial infarction,
      revascularization, and bleeding. Relative to bare metal stent use, drug-eluting
      stent use was associated with similar improved long-term outcomes in both sexes:
      death (women: adjusted HR, 0.78; 95% CI, 0.76-0.81; men: HR, 0.77; 95% CI, 0.74
      0.79), myocardial infarction (women: HR, 0.79; 95% CI, 0.74-0.84; men: HR, 0.81;
      95% CI, 0.77-0.85), and revascularization (women: HR, 0.93; 95% CI, 0.90-0.97;
      men: HR, 0.91; 95% CI, 0.88-0.94). There was no interaction between sex and stent
      type for long-term outcomes. CONCLUSIONS: In contemporary coronary stenting,
      women have a slightly higher procedural risk than men but have better long-term
      survival. In both sexes, use of a drug-eluting stent is associated with lower
      long-term likelihood for death, myocardial infarction, and revascularization.

PMID- 22988010
TI  - Our time: a call to save preventable death from cardiovascular disease (heart
      disease and stroke).

PMID- 22988011
TI  - Interplay between mesenchymal stem cells and lymphocytes: implications for
      immunotherapy and tissue regeneration.
AB  - In addition to their potential for replacing damaged and diseased tissues by
      differentiating into tissue-specific cells, mesenchymal stem cells (MSCs) have
      been found to interact closely with immune cells, such as lymphocytes. In this
      review, we will discuss current research regarding the immunomodulatory
      properties of MSCs and the effects of lymphocytes on MSCs. We will suggest how
      these findings could be translated to potential clinical treatment. MSCs can
      regulate immune response by inducing activated T-cell apoptosis through the FAS
      ligand (FASL)/FAS-mediated death pathway via cell-cell contact, leading to up
      regulation of regulatory T-cells (Tregs), which ultimately results in immune
      tolerance. Conversely, lymphocytes can impair survival and osteogenic
      differentiation of implanted MSCs by secreting the pro-inflammatory cytokines IFN
      gamma and TNF-alpha and/or through the FASL/FAS-mediated death pathway, thereby
      negatively affecting MSC-mediated tissue regeneration. One novel strategy to
      improve MSC-based tissue engineering involves the reduction of IFN-gamma and TNF
      alpha concentration by systemic infusion of Tregs or local application of
      aspirin. Further understanding of the mechanisms underlying the interplay between
      lymphocytes and MSCs may be helpful in the development of promising approaches to
      improve cell-based regenerative medicine and immune therapies.

PMID- 22988012
TI  - Human oral mucosa and gingiva: a unique reservoir for mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) represent a heterogeneous population of progenitor
      cells with self-renewal and multipotent differentiation potential. Aside from
      their regenerative role, extensive in vitro and in vivo studies have demonstrated
      that MSCs are capable of potent immunomodulatory effects on a variety of innate
      and adaptive immune cells. In this article, we will review recent experimental
      studies on the characterization of a unique population of MSCs derived from human
      oral mucosa and gingiva, especially their immunomodulatory and anti-inflammatory
      functions and their application in the treatment of several in vivo models of
      inflammatory diseases. The ease of isolation, accessible tissue source, and rapid
      ex vivo expansion, with maintenance of stable stem-cell-like phenotypes, render
      oral mucosa- and gingiva-derived MSCs a promising alternative cell source for MSC
      based therapies.

PMID- 22988013
TI  - Selenite-induced hormonal and signalling mechanisms during root growth of
      Arabidopsis thaliana L.
AB  - Selenium excess can cause toxicity symptoms, e.g. root growth inhibition in non
      hyperaccumulator plants such as Arabidopsis. Selenite-induced hormonal and
      signalling mechanisms in the course of development are poorly understood;
      therefore this study set out to investigate the possible hormonal and signalling
      processes using transgenic and mutant Arabidopsis plants. Significant alterations
      were observed in the root architecture of the selenite-treated plants, due to the
      loss of cell viability in the root apex. During mild selenite excess, the plants
      showed symptoms of the morphogenic response: primary root (PR) shortening and
      increased initiation of laterals, ensuring better nutrient and water uptake and
      stress acclimation. As well as lower meristem cell activity, the second reason
      for the Se-induced growth hindrance is the hormonal imbalance, since the in situ
      expression of the auxin-responsive DR5::GUS, and consequently the auxin levels,
      significantly decreased, while that of the cytokinin-inducible ARR5::GUS and the
      ethylene biosynthetic ACS8::GUS increased. It is assumed that auxin and ethylene
      might positively regulate selenium tolerance, since reduced levels of them
      resulted in sensitivity. Moreover, high cytokinin levels caused notable selenite
      tolerance. During early seedling development, nitric oxide (NO) contents
      decreased but hydrogen peroxide levels increased reflecting the antagonism
      between the two signal molecules during Se excess. High levels of NO in gsnor1-3,
      lead to selenite tolerance, while low NO production in nia1nia2 resulted in
      selenite sensitivity. Consequently, NO derived from the root nitrate reductase
      activity is responsible for the large-scale selenite tolerance in Arabidopsis.

PMID- 22988014
TI  - Immune modulation by group B Streptococcus influences host susceptibility to
      urinary tract infection by uropathogenic Escherichia coli.
AB  - Urinary tract infection (UTI) is most often caused by uropathogenic Escherichia
      coli (UPEC). UPEC inoculation into the female urinary tract (UT) can occur
      through physical activities that expose the UT to an inherently polymicrobial
      periurethral, vaginal, or gastrointestinal flora. We report that a common
      urogenital inhabitant and opportunistic pathogen, group B Streptococcus (GBS),
      when present at the time of UPEC exposure, undergoes rapid UPEC-dependent
      exclusion from the murine urinary tract, yet it influences acute UPEC-host
      interactions and alters host susceptibility to persistent outcomes of bladder and
      kidney infection. GBS presence results in increased UPEC titers in the bladder
      lumen during acute infection and reduced inflammatory responses of murine
      macrophages to live UPEC or purified lipopolysaccharide (LPS), phenotypes that
      require GBS mimicry of host sialic acid residues. Taken together, these studies
      suggest that despite low titers, the presence of GBS at the time of polymicrobial
      UT exposure may be an overlooked risk factor for chronic pyelonephritis and
      recurrent UTI in susceptible groups, even if it is outcompeted and thus absent by
      the time of diagnosis.

PMID- 22988015
TI  - Dectin-1 is not required for controlling Candida albicans colonization of the
      gastrointestinal tract.
AB  - Candida albicans is normally found as a commensal microbe, commonly colonizing
      the gastrointestinal tract in humans. However, this fungus can also cause mucosal
      and systemic infections once immune function is compromised. Dectin-1 is an
      innate pattern recognition receptor essential for the control of fungal
      infections in both mice and humans; however, its role in the control of C.
      albicans colonization of the gastrointestinal tract has not been defined. Here,
      we demonstrate that in mice dectin-1 is essential for the control of
      gastrointestinal invasion during systemic infection, with dectin-1 deficiency
      associating with impaired fungal clearance and dysregulated cytokine production.
      Surprisingly, however, following oral infection, dectin-1 was not required for
      the control of mucosal colonization of the gastrointestinal tract, in terms of
      either fungal burdens or cytokine response. Thus, in mice, dectin-1 is essential
      for controlling systemic infection with C. albicans but appears to be redundant
      for the control of gastrointestinal colonization.

PMID- 22988016
TI  - Meningococcal PilV potentiates Neisseria meningitidis type IV pilus-mediated
      internalization into human endothelial and epithelial cells.
AB  - The type IV pilus of Neisseria meningitidis is the major factor for meningococcal
      adhesion to host cells. In this study, we showed that a mutant of N. meningitidis
      pilV, a minor pilin protein, internalized less efficiently to human endothelial
      and epithelial cells than the wild-type strain. Matrix-assisted laser desorption
      ionization-time of flight mass spectrometry and electrospray ionization tandem
      mass spectrometry analyses showed that PilE, the major subunit of pili, was less
      glycosylated at its serine 62 residue (Ser62) in the DeltapilV mutant than in the
      pilV(+) strain, whereas phosphoglycerol at PilE Ser93 and phosphocholine at PilE
      Ser67 were not changed. Introduction of the pglL mutation, which results in
      complete loss of O-linked glycosylation from Ser62, slightly reduced N.
      meningitidis internalization into human brain microvascular endothelial cells,
      whereas the addition of the DeltapilV mutation greatly reduced N. meningitidis
      internalization. The accumulation of ezrin, which is part of the cytoskeleton ERM
      family, was observed with pilV(+), DeltapglL, and pilE(S62A) strains but not with
      the DeltapilV mutant. These results suggested that whereas N. meningitidis pilin
      originally had an adhesive activity that was less affected by minor pilin
      proteins, the invasive function evolved with incorporation of the PilV protein
      into the pili to promote the N. meningitidis internalization into human cells.

PMID- 22988017
TI  - Transposon mutagenesis of Salmonella enterica serovar Enteritidis identifies
      genes that contribute to invasiveness in human and chicken cells and survival in
      egg albumen.
AB  - Salmonella enterica serovar Enteritidis is an important food-borne pathogen, and
      chickens are a primary reservoir of human infection. While most knowledge about
      Salmonella pathogenesis is based on research conducted on Salmonella enterica
      serovar Typhimurium, S. Enteritidis is known to have pathobiology specific to
      chickens that impacts epidemiology in humans. Therefore, more information is
      needed about S. Enteritidis pathobiology in comparison to that of S. Typhimurium.
      We used transposon mutagenesis to identify S. Enteritidis virulence genes by
      assay of invasiveness in human intestinal epithelial (Caco-2) cells and chicken
      liver (LMH) cells and survival within chicken (HD-11) macrophages as a surrogate
      marker for virulence. A total of 4,330 transposon insertion mutants of an
      invasive G1 Nal(r) strain were screened using Caco-2 cells. This led to the
      identification of attenuating mutations in a total of 33 different loci, many of
      which include genes previously known to contribute to enteric infection (e.g.,
      Salmonella pathogenicity island 1 [SPI-1], SPI-4, SPI-5, CS54, fliH, fljB, csgB,
      spvR, and rfbMN) in S. Enteritidis and other Salmonella serovars. Several genes
      or genomic islands that have not been reported previously (e.g., SPI-14, ksgA,
      SEN0034, SEN2278, and SEN3503) or that are absent in S. Typhimurium or in most
      other Salmonella serovars (e.g., pegD, SEN1152, SEN1393, and SEN1966) were also
      identified. Most mutants with reduced Caco-2 cell invasiveness also showed
      significantly reduced invasiveness in chicken liver cells and impaired survival
      in chicken macrophages and in egg albumen. Consequently, these genes may play an
      important role during infection of the chicken host and also contribute to
      successful egg contamination by S. Enteritidis.

PMID- 22988019
TI  - Involvement of signal regulatory protein alpha, a negative regulator of Toll-like
      receptor signaling, in impairing the MyD88-independent pathway and intracellular
      killing of Burkholderia pseudomallei-infected mouse macrophages.
AB  - The facultative intracellular gram-negative bacterium Burkholderia pseudomallei
      is the causative agent of melioidosis and is known for its ability to evade the
      Toll-like receptor (TLR)-mediated innate immune response. Previously it has been
      demonstrated that this bacterium was able to suppress the MyD88-independent
      pathway and can survive macrophage intracellular killing. However, the underlying
      mechanisms responsible for the suppression of this pathway are not fully
      understood. In the present study, we showed that both living and heat-killed B.
      pseudomallei bacteria restrict the TLR signaling response, particularly
      macrophage inducible nitric oxide synthase (iNOS) expression, by preventing
      downregulation of constitutively expressed signal regulatory protein alpha
      (SIRPalpha) molecule, a known negative regulator of TLR signaling. In contrast, a
      lipopolysaccharide (LPS) mutant of B. pseudomallei, a less virulent strain, was
      able to downregulate SIRPalpha expression in mouse macrophages. However,
      depletion of constitutively expressed SIRPalpha was able to induce the gene
      expression downstream of TLR signaling pathways (particularly the MyD88
      independent pathway), such as that of the iNOS gene, leading to enhanced
      macrophage intracellular killing of B. pseudomallei. Induction of gene expression
      was consistent with the enhanced degradation pattern of IkappaBalpha with
      SIRPalpha depletion. Additionally, the downregulation of SIRPalpha expression
      with upregulation of iNOS was observed when the macrophages were pretreated with
      gamma interferon (IFN-gamma) prior to the infection, suggesting that the enhanced
      intracellular killing of bacteria by IFN-gamma is associated with the decreased
      SIRPalpha expression. Altogether our findings demonstrate that B. pseudomallei
      evades macrophage intracellular killing by preventing the downregulation of
      SIRPalpha that results in the inhibition of gene expression downstream of the
      MyD88-independent pathway.

PMID- 22988018
TI  - Nocardia farcinica activates human dendritic cells and induces secretion of
      interleukin-23 (IL-23) rather than IL-12p70.
AB  - Studying the interaction of dendritic cells (DCs) with bacteria controlled by T
      cell-mediated immune responses may reveal novel adjuvants for the induction of
      cellular immunity. Murine studies and the observation that nocardias infect
      predominantly immunosuppressed patients have suggested that these bacteria may
      possess an adjuvant potential. Moreover, adjuvants on the basis of the nocardial
      cell wall have been applied in clinical studies. Since the handling of adjuvants
      by DCs may determine the type of immune responses induced by a vaccine, the
      present study aimed at investigating the interaction of immature human monocyte
      derived DCs with live or inactivated Nocardia farcinica in vitro and determining
      the cellular phenotypic changes as well as alterations in characteristic
      functions, such as phagocytosis, induction of T-cell proliferation, and cytokine
      secretion. Human DCs ingested N. farcinica and eradicated the bacterium
      intracellularly. DCs exposed to inactivated N. farcinica were activated, i.e.,
      they developed a mature phenotype, downregulated their phagocytic capacity, and
      stimulated allogeneic T cells in mixed leukocyte reactions. Soluble factors were
      not involved in this process. To elucidate the potential adjuvant effect of N.
      farcinica on the induction of T-cell-mediated immune responses, we characterized
      the cytokines produced by nocardia-exposed DCs and detected substantial amounts
      of tumor necrosis factor alpha (TNF-alpha) and interleukin-12 p40 (IL-12p40).
      However, nocardia-treated DCs secreted only small amounts of IL-12p70, which were
      significantly smaller than the amounts of IL-23. Thus, N. farcinica activates
      DCs, but adjuvants based on this bacterium may have only a limited capacity to
      induce Th1 immune responses.

PMID- 22988020
TI  - Susceptibility to progressive Cryptococcus neoformans pulmonary infection is
      regulated by loci on mouse chromosomes 1 and 9.
AB  - Genetic factors that regulate the pathogenesis of pneumonia caused by the fungus
      Cryptococcus neoformans are poorly understood. Through a phenotypic strain survey
      we observed that inbred C3H/HeN mice develop a significantly greater lung fungal
      burden than mice of the resistant CBA/J strain 4 weeks following intratracheal
      infection with C. neoformans ATCC 24067. The aim of the present study was to
      characterize the inflammatory response of C3H/HeN mice following C. neoformans
      pulmonary infection and to identify genetic loci that regulate host defense.
      Following cryptococcal infection, C3H/HeN mice demonstrated a Th2 immune response
      with heightened airway and tissue eosinophilia, goblet cell metaplasia, and
      significantly higher lung interleukin-5 (IL-5) and IL-13 protein expression
      relative to CBA/J mice. Conversely, CBA/J mice exhibited greater airway and
      tissue neutrophilia that was associated with significantly higher pulmonary
      expression of gamma interferon, CXCL10, and IL-17 proteins than C3H/HeN mice.
      Using the fungal burden at 4 weeks postinfection as a phenotype, genome-wide
      quantitative trait locus (QTL) analysis among 435 segregating (C3H/HeN * CBA/J)F2
      (C3HCBAF2) hybrids identified two significant QTLs on chromosomes 1 (Cnes4) and 9
      (Cnes5) that control susceptibility to cryptococcal pneumonia in an additive
      manner. Susceptible C3H/HeN mice carry a resistance allele at Cnes4 and a
      susceptibility allele at Cnes5. These studies reveal additional genetic
      complexity of the host response to C. neoformans that is associated with
      divergent patterns of pulmonary inflammation.

PMID- 22988021
TI  - Cyclic di-GMP stimulates biofilm formation and inhibits virulence of Francisella
      novicida.
AB  - Francisella tularensis is a gram-negative bacterium that is highly virulent in
      humans, causing the disease tularemia. F. novicida is closely related to F.
      tularensis and exhibits high virulence in mice, but it is avirulent in healthy
      humans. An F. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two
      proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that
      modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE
      encoding protein genes are present in the F. tularensis genome. F. novicida
      strains lacking either the two DGC/PDE genes (cdgA and cdgB) or the entire gene
      cluster (strain KKF457) are defective for biofilm formation. In addition,
      expression of CdgB or a heterologous DGC in strain KKF457 stimulated F. novicida
      biofilms, even in a strain lacking the biofilm regulator QseB. Genetic evidence
      suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC. The
      F. novicida qseB strain showed reduced cdgA and cdgB transcript levels,
      demonstrating an F. novicida biofilm signaling cascade that controls cdGMP
      levels. Interestingly, KKF457 with elevated cdGMP levels exhibited a decrease in
      intramacrophage replication and virulence in mice, as well as increased growth
      yields and biofilm formation in vitro. Microarray analyses revealed that cdGMP
      stimulated the transcription of a chitinase (ChiB) known to contribute to biofilm
      formation. Our results indicate that elevated cdGMP in F. novicida stimulates
      biofilm formation and inhibits virulence. We suggest that differences in human
      virulence between F. novicida and F. tularensis may be due in part to the absence
      of cdGMP signaling in F. tularensis.

PMID- 22988023
TI  - The path of screw insertion for stabilization of the scapholunate joint. A
      radiological study.

PMID- 22988022
TI  - Reversible inhibition of Chlamydia trachomatis infection in epithelial cells due
      to stimulation of P2X(4) receptors.
AB  - Bacterial infections of the mucosal epithelium are a major cause of human
      disease. The prolonged presence of microbial pathogens stimulates inflammation of
      the local tissues, which leads to changes in the molecular composition of the
      extracellular milieu. A well-characterized molecule that is released to the
      extracellular milieu by stressed or infected cells is extracellular ATP and its
      ecto-enzymatic degradation products, which function as signaling molecules
      through ligation of purinergic receptors. There has been little information,
      however, on the effects of the extracellular metabolites on bacterial growth in
      inflamed tissues. Millimolar concentrations of ATP have been previously shown to
      inhibit irreversibly bacterial infection through ligation of P2X(7) receptors. We
      show here that the proinflammatory mediator, ATP, is released from Chlamydia
      trachomatis-infected epithelial cells. Moreover, further stimulation of the
      infected cells with micromolar extracellular ADP or ATP significantly impairs the
      growth of the bacteria, with a profile characteristic of the involvement of
      P2X(4) receptors. A specific role for P2X(4) was confirmed using cells
      overexpressing P2X(4). The chlamydiae remain viable and return to normal growth
      kinetics after removal of the extracellular stimulus, similar to responses
      previously described for persistence of chlamydial infection.

PMID- 22988024
TI  - The 'chased method' of mini screw fixation: a percutaneous surgical approach to
      treating mallet fractures.

PMID- 22988025
TI  - Ice cream scoop test: a novel clinical test to diagnose extensor carpi ulnaris
      instability.

PMID- 22988027
TI  - Swimming in the intermediate Reynolds range: kinematics of the pteropod Limacina
      helicina.
AB  - Limacina helicina (1-3 mm) lives in the environment that straddles both inertial
      and viscous regimes. In this intermediate Reynolds range (10(0)-10(3)), an
      oscillating appendage may use either drag-based or lift-based locomotion. The
      swimming motion of L. helicina was investigated to determine its mechanics and
      whether features of rowing or flying gaits were present. Mean speeds, stroke
      frequencies, and general paths were revealed from the trajectories of free
      swimming individuals. High-speed videography of tethered animals enabled a
      detailed analysis of stroke parameters involved in L. helicina swimming. During
      swimming episodes, L. helicina ascend along a sawtooth trajectory in mostly
      linear and sometimes helical paths. Mean speeds varied from 13 to 44 mm/s for
      straight ascents and slightly more for helical paths. During swimming, the stroke
      cycle caused oscillations in body orientation, whereas sinking is characterized
      by smooth straight descents. Sinking speeds of 5-45 mm s(-1) were observed. Wing
      beat frequencies decreased with body size from 4.5 to 9.4 Hz. The wing stroke is
      a complex, three-dimensional motion that does not perfectly correspond to
      theoretical concepts of drag-based or lift-based propulsion. Instead, the
      repertoire of movements indicates that elements of both rowing and flying are
      incorporated in the swimming of L. helicina with the added element of rotation.
      Size-dependent differences in stroke mechanics are described. Of particular note
      is evidence that a clap-and-fling mechanism is applied during the stroke cycle.

PMID- 22988028
TI  - Neonatal autoimmune diseases.

PMID- 22988026
TI  - Using computational and mechanical models to study animal locomotion.
AB  - Recent advances in computational methods have made realistic large-scale
      simulations of animal locomotion possible. This has resulted in numerous
      mathematical and computational studies of animal movement through fluids and over
      substrates with the purpose of better understanding organisms' performance and
      improving the design of vehicles moving through air and water and on land. This
      work has also motivated the development of improved numerical methods and
      modeling techniques for animal locomotion that is characterized by the
      interactions of fluids, substrates, and structures. Despite the large body of
      recent work in this area, the application of mathematical and numerical methods
      to improve our understanding of organisms in the context of their environment and
      physiology has remained relatively unexplored. Nature has evolved a wide variety
      of fascinating mechanisms of locomotion that exploit the properties of complex
      materials and fluids, but only recently are the mathematical, computational, and
      robotic tools available to rigorously compare the relative advantages and
      disadvantages of different methods of locomotion in variable environments.
      Similarly, advances in computational physiology have only recently allowed
      investigators to explore how changes at the molecular, cellular, and tissue
      levels might lead to changes in performance at the organismal level. In this
      article, we highlight recent examples of how computational, mathematical, and
      experimental tools can be combined to ultimately answer the questions posed in
      one of the grand challenges in organismal biology: "Integrating living and
      physical systems."

PMID- 22988029
TI  - Diagnosis of antiphospholipid syndrome in routine clinical practice.
AB  - The updated international consensus criteria for definite antiphospholipid
      syndrome (APS) are useful for scientific clinical studies. However, there remains
      a need for diagnostic criteria for routine clinical use. We audited the results
      of routine antiphospholipid antibodies (aPLs) in a cohort of 193 consecutive
      patients with aPL positivity-based testing for lupus anticoagulant (LA), IgG and
      IgM anticardiolipin (aCL) and anti-beta(2)glycoprotein-1 antibodies
      (abeta(2)GPI). Medium/high-titre aCL/abeta(2)GPI was defined as >99th percentile.
      Low-titre aCL/abeta(2)GPI positivity (>95(th )< 99(th) percentile) was considered
      positive for obstetric but not for thrombotic APS. One hundred of the 145
      patients fulfilled both clinical and laboratory criteria for definite APS. Twenty
      six women with purely obstetric APS had persistent low-titre aCL and/or
      abeta(2)GPI. With the inclusion of these patients, 126 of the 145 patients were
      considered to have APS. Sixty-seven out of 126 patients were LA-negative, of whom
      12 had aCL only, 37 had abeta(2)GPI only and 18 positive were for both. The
      omission of aCL or abeta(2)GPI testing from investigation of APS would have led
      to a failure to diagnose APS in 9.5% and 29.4% of patients, respectively. Our
      data suggest that LA, aCL and abeta(2)GPI testing are all required for the
      accurate diagnosis of APS and that low-titre antibodies should be included in the
      diagnosis of obstetric APS.

PMID- 22988031
TI  - Scavenger receptor in fish is a lipopolysaccharide recognition molecule involved
      in negative regulation of NF-kappaB activation by competing with TNF receptor
      associated factor 2 recruitment into the TNF-alpha signaling pathway.
AB  - Scavenger receptors (SRs) play crucial roles in innate immunity by acting as
      pattern recognition receptors. Although SRs are widely documented in mammals,
      data on their occurrence and functions in ancient vertebrates are limited. In
      this study, we report, to our knowledge, the first cloning and functional
      characterization of an SR molecule from teleost fish (Tetraodon nigroviridis).
      This SR (TnSR) was identified as a homolog to mammalian scavenger receptor class
      A member 5 with the conserved structure of a class A SR. TnSR contained
      multidomains in a type II transmembrane receptor, including an SR cysteine-rich
      domain, two coiled-coil collagenous domains, a transmmebrane domain, and a short
      N-terminal intracellular region with an unexpected TNFR-associated factor 2
      binding consensus motif similar to that in human MSR molecules. Phylogenetic
      analysis suggested that TnSR may be an ancient member of class A SRs resulting
      from the close relationship between scavenger receptor class A member 5 and
      macrophage SR in vertebrates associated with the subtle differences in TnSR
      structure. Subcellular localization analysis showed that TnSR was a cell membrane
      receptor with homotrimer forms involved in the recognition and internalization of
      LPS from surface membranes into lysosomes. Functionally, TnSR expression was
      dramatically induced by LPS stimulation. TnSR served as a negative regulator in
      LPS-induced NF-kappaB activation by the competitive recruitment of TNFR
      associated factor 2 from the TNF-alpha signaling pathway. To our knowledge, this
      is the first report showing that SR plays an inhibitory role in LPS-elicited
      inflammation by cross-talking with the TNF-alpha inflammatory pathway. These
      findings contribute to a better understanding of the biological and evolutionary
      history of the SR family.

PMID- 22988030
TI  - Abelson tyrosine kinase controls phagosomal acidification required for killing of
      Mycobacterium tuberculosis in human macrophages.
AB  - The mechanisms that regulate the acidification of intracellular compartments are
      key to host defense against pathogens. In this paper, we demonstrate that Abl
      tyrosine kinase, a master switch for cell growth and trafficking of intracellular
      organelles, controls the acidification of lysosomes in human macrophages.
      Pharmacological inhibition by imatinib and gene silencing of Abelson (Abl)
      tyrosine kinase reduced the lysosomal pH in human macrophages by increasing the
      transcription and expression of the proton pumping enzyme vacuolar-type H(+)
      adenosine triphosphatase. Because lysosomal acidification is required for
      antimicrobial activity against intracellular bacteria, we determined the effect
      of imatinib on the growth of the major human pathogen Mycobacterium tuberculosis.
      Imatinib limited the multiplication of M. tuberculosis, and growth restriction
      was dependent on acidification of the mycobacterial compartment. The effects of
      imatinib were also active in vivo because circulating monocytes from imatinib
      treated leukemia patients were more acidic than monocytes from control donors.
      Importantly, sera from imatinib-treated patients triggered acidification and
      growth restriction of M. tuberculosis in macrophages. In summary, our results
      identify the control of phagosomal acidification as a novel function of Abl
      tyrosine kinase and provide evidence that the regulation occurs on the level of
      the vacuolar-type H(+)-adenosine triphosphatase. Given the efficacy of imatinib
      in a mouse model of tuberculosis and our finding that orally administered
      imatinib increased the ability of human serum to trigger growth reduction of
      intracellular M. tuberculosis, clinical evaluation of imatinib as a complementary
      therapy of tuberculosis, in particular multidrug or extremely drug-resistant
      disease, is warranted.

PMID- 22988033
TI  - Prevention of virus-induced type 1 diabetes with antibiotic therapy.
AB  - Microbes were hypothesized to play a key role in the progression of type 1
      diabetes (T1D). We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced
      T1D to test the hypothesis that the intestinal microbiota is involved in the
      mechanism leading to islet destruction. Treating LEW1.WR1 rats with KRV and a
      combination of trimethoprim and sulfamethoxazole (Sulfatrim) beginning on the day
      of infection protected the rats from insulitis and T1D. Pyrosequencing of
      bacterial 16S rRNA and quantitative RT-PCR indicated that KRV infection resulted
      in a transient increase in the abundance of Bifidobacterium spp. and Clostridium
      spp. in fecal samples from day 5- but not day 12-infected versus uninfected
      animals. Similar alterations in the gut microbiome were observed in the jejunum
      of infected animals on day 5. Treatment with Sulfatrim restored the level of
      intestinal Bifidobacterium spp. and Clostridium spp. We also observed that virus
      infection induced the expression of KRV transcripts and the rapid upregulation of
      innate immune responses in Peyer's patches and pancreatic lymph nodes. However,
      antibiotic therapy reduced the virus-induced inflammation as reflected by the
      presence of lower amounts of proinflammatory molecules in both the Peyer's
      patches and pancreatic lymph nodes. Finally, Sulfatrim treatment reduced the
      number of B cells in Peyer's patches and downmodulated adaptive immune responses
      to KRV, but did not interfere with antiviral Ab responses or viral clearance from
      the spleen, pancreatic lymph nodes, and serum. The data suggest that gut
      microbiota may be involved in promoting virus-induced T1D in the LEW1.WR1 rat
      model.

PMID- 22988035
TI  - The thymic niche does not limit development of the naturally diverse population
      of mouse regulatory T lymphocytes.
AB  - Thymus-derived CD4(+)Foxp3(+) regulatory T lymphocytes (Tregs) play a central
      role in the suppression of immune responses to self-antigens and thus avoid
      autoimmune disorders. It remains unclear if the specialized thymic niche controls
      the number of differentiating Tregs. We investigated development of murine Tregs
      from precursors expressing the naturally very large repertoire of TCRs. By
      analyzing their developmental kinetics, we observed that differentiating Tregs
      dwell in the thymus ~1 d longer than their conventional T cell counterparts. By
      generating hematopoietic chimeras with very low proportions of trackable
      precursors, we could follow individual waves of developing T cells in the thymus.
      We observed strongly increased proportions of Tregs at the end of the waves,
      confirming that these cells are the last to leave the thymus. To assess whether
      the thymic niche limits Treg development, we generated hematopoietic chimeras in
      which very few T cell precursors could develop. The substantial increase in the
      proportion of Tregs we found in these mice suggested a limiting role of the
      thymic niche; however, this increase was accounted for entirely by the prolonged
      thymic dwell time of Tregs. We conclude that, when precursors express a naturally
      diverse TCR repertoire, the thymic niche does not limit differentiation of Tregs.

PMID- 22988034
TI  - Foxp3 expression is required for the induction of therapeutic tissue tolerance.
AB  - CD4(+)Foxp3(+) regulatory T cells (Treg) are essential for immune homeostasis and
      maintenance of self-tolerance. They are produced in the thymus and also generated
      de novo in the periphery in a TGF-beta-dependent manner. Foxp3(+) Treg are also
      required to achieve tolerance to transplanted tissues when induced by coreceptor
      or costimulation blockade. Using TCR-transgenic mice to avoid issues of
      autoimmune pathology, we show that Foxp3 expression is both necessary and
      sufficient for tissue tolerance by coreceptor blockade. Moreover, the known need
      in tolerance induction for TGF-beta signaling to T cells can wholly be explained
      by its role in induction of Foxp3, as such signaling proved dispensable for the
      suppressive process. We analyzed the relative contribution of TGF-beta and Foxp3
      to the transcriptome of TGF-beta-induced Treg and showed that TGF-beta elicited a
      large set of downregulated signature genes. The number of genes uniquely
      modulated due to the influence of Foxp3 alone was surprisingly limited.
      Retroviral-mediated conditional nuclear expression of Foxp3 proved sufficient to
      confer transplant-suppressive potency on CD4(+) T cells and was lost once nuclear
      Foxp3 expression was extinguished. These data support a dual role for TGF-beta
      and Foxp3 in induced tolerance, in which TGF-beta stimulates Foxp3 expression,
      for which sustained expression is then associated with acquisition of tolerance.

PMID- 22988036
TI  - Ten top considerations in pediatric tympanoplasty.
AB  - Tympanoplasty in children poses some different challenges from the same procedure
      in adults. The aim of the current article is to review 10 important
      considerations in pediatric tympanoplasty that focus on these differences and
      help to optimize the chance of successful outcome.

PMID- 22988032
TI  - Kruppel-like factor 2 modulates CCR5 expression and susceptibility to HIV-1
      infection.
AB  - CCR5, a cell surface molecule critical for the transmission and spread of HIV-1,
      is dynamically regulated during T cell activation and differentiation. The
      molecular mechanism linking T cell activation to modulation of CCR5 expression
      remains undefined. Kruppel-like factor 2 (KLF2) is a transcription factor that
      promotes quiescence, survival, and in part by modulating chemokine receptor
      levels, induces homing to secondary lymphoid organs. Given the relationship
      between T cell activation and chemokine receptor expression, we tested whether
      the abundance of KLF2 after T cell activation regulates CCR5 expression and,
      thus, susceptibility of a T cell to CCR5-dependent HIV-1 strains (R5). We
      observed a strong correlation between T cell activation, expression of KLF2 and
      CCR5, and susceptibility to infection. To directly measure how KLF2 affects CCR5
      regulation, we introduced small interfering RNA targeting KLF2 expression and
      demonstrated that reduced KLF2 expression also resulted in less CCR5. Chromatin
      immunoprecipitation assays identified KLF2 bound to the CCR5 promoter in resting
      but not CD3/28 activated T cells, suggesting that KLF2 directly regulates CCR5
      expression. Introduction of KLF2 under control of a heterologous promoter could
      restore CCR5 expression and R5 susceptibility to CD3/28 costimulated T cells and
      some transformed cell lines. Thus, KLF2 is a host factor that modulates CCR5
      expression in CD4 T cells and influences susceptibility to R5 infection.

PMID- 22988037
TI  - Comparison of pathological outcomes of active surveillance candidates who
      underwent radical prostatectomy using contemporary protocols at a high-volume
      Korean center.
AB  - OBJECTIVE: We compared contemporary active surveillance protocols based on
      pathological outcomes in patients who underwent radical prostatectomy. METHODS:
      We identified the experimental cohort from prostate cancer patients who underwent
      radical prostatectomy between 2001 and 2011, and who met the inclusion criteria
      of five published active surveillance protocols, namely Johns Hopkins Medical
      Institution, University of California at San Francisco, Memorial Sloan-Kettering
      Cancer Center, University of Miami and Prostate Cancer Research International:
      Active Surveillance. To compare each protocol, we evaluated the pathological
      outcomes and calculated the sensitivity, specificity and accuracy for each
      protocol according to the proportion of organ-confined Gleason<=6 disease.
      RESULTS: Overall, 376 patients met the inclusion criteria of the active
      surveillance protocols with 61, 325, 222, 212 and 206 patients meeting the
      criteria of the Johns Hopkins Medical Institution, University of California at
      San Francisco, Memorial Sloan-Kettering Cancer Center, University of Miami and
      Prostate Cancer Research International: Active Surveillance protocols,
      respectively. The sensitivity and specificity values of the five protocols,
      respectively, were 0.199 and 0.882 in Johns Hopkins Medical Institution, 0.855
      and 0.124 in University of California at San Francisco, 0.638 and 0.468 in
      Memorial Sloan-Kettering Cancer Center, 0.599 and 0.479 in University of Miami,
      and 0.609 and 0.527 in Prostate Cancer Research International: Active
      Surveillance. In terms of both the sensitivity and specificity, Prostate Cancer
      Research International: Active Surveillance was the most balanced protocol. In
      addition, Prostate Cancer Research International: Active Surveillance showed a
      more accurate performance for favourable pathological outcomes than the others.
      However, using the area under the curve to compare the discriminative ability of
      each protocol, there were no statistically significant differences. CONCLUSIONS:
      The contemporary active surveillance protocols showed similar pathological
      characteristics in patients who had undergone radical prostatectomy. However, we
      concluded that the Prostate Cancer Research International: Active Surveillance
      protocol would be most helpful to Korean populations in choosing candidates for
      active surveillance considering the balance between sensitivity and specificity
      and the accuracy of diagnosis.

PMID- 22988038
TI  - Prevalence of breast cancer risk factors in Japan.
AB  - OBJECTIVE: Breast cancer is the most common type of cancer in women worldwide.
      Although the incidence of breast cancer is still on an increasing trend, there
      are few studies concerning breast cancer risk factors in Japan. Therefore, we
      conducted an Internet survey investigating the prevalence of risk factors for
      breast cancer. METHODS: We conducted an Internet survey using opt-in panels in
      women aged from 20 to 70 years. The survey items consisted of potential and
      proven risk factors for breast cancer such as age at menarche, menopausal status,
      premenopausal use of oral contraceptives, postmenopausal use of hormones, parity,
      height, alcohol consumption and family history of breast cancer. RESULTS:
      Subjects comprised 2002 persons who were matched for sex, age and residential
      area with the National Census in 2005. Statistically significant trends were
      observed for most factors: age at menarche is becoming lower, age at first birth
      is higher, height is higher, the proportion of women who have given birth is
      smaller and the proportion of women who drink alcohol is larger. CONCLUSIONS: We
      showed a clear increase in the prevalence of risk factors for breast cancer.
      Based on the results, the incidence of breast cancer in Japan may be increasing
      for at least a few decades.

PMID- 22988039
TI  - HSL-knockout mouse testis exhibits class B scavenger receptor upregulation and
      disrupted lipid raft microdomains.
AB  - There is a tight relationship between fertility and changes in cholesterol
      metabolism during spermatogenesis. In the testis, class B scavenger receptors (SR
      B) SR-BI, SR-BII, and LIMP II mediate the selective uptake of cholesterol esters
      from HDL, which are hydrolyzed to unesterified cholesterol by hormone-sensitive
      lipase (HSL). HSL is critical because HSL knockout (KO) male mice are sterile.
      The aim of the present work was to determine the effects of the lack of HSL in
      testis on the expression of SR-B, lipid raft composition, and related cell
      signaling pathways. HSL-KO mouse testis presented altered spermatogenesis
      associated with decreased sperm counts, sperm motility, and infertility. In wild
      type (WT) testis, HSL is expressed in elongated spermatids; SR-BI, in Leydig
      cells and spermatids; SR-BII, in spermatocytes and spermatids but not in Leydig
      cells; and LIMP II, in Sertoli and Leydig cells. HSL knockout male mice have
      increased expression of class B scavenger receptors, disrupted caveolin-1
      localization in lipid raft plasma membrane microdomains, and activated phospho
      ERK, phospho-AKT, and phospho-SRC in the testis, suggesting that class B
      scavenger receptors are involved in cholesterol ester uptake for steroidogenesis
      and spermatogenesis in the testis.

PMID- 22988040
TI  - Benefits and harms of detecting clinically occult breast cancer.
AB  - Over the last few decades there has been an increase in the use of strategies to
      detect clinically occult breast cancer with the aim of achieving diagnosis at an
      earlier stage when prognosis may be improved. Such strategies include screening
      mammography in healthy women, diagnostic imaging and axillary staging in those
      diagnosed with breast cancer, and the use of follow-up imaging for the early
      detection of recurrent or metastatic disease. Some of these strategies are
      established, whereas for others there are inconsistent supportive data. Although
      the potential benefit of early detection of clinically occult breast cancer seems
      intuitive, use of such strategies can also be associated with harm. In this
      commentary, we provide an extended discussion on the potential benefits and harms
      of the routine and frequent use of screening interventions to detect clinically
      occult breast cancer and question whether we may be causing more harm than good.

PMID- 22988041
TI  - Validation of the Polish version of the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire - Core 15 - Palliative Care in
      patients with advanced cancer.
AB  - BACKGROUND: Limited data exist on the validation of the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire - Core 15 -
      Palliative Care in advanced cancer patients. AIM: To adapt the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire -
      Core 15 - Palliative Care to the Polish clinical setting and to evaluate its
      psychometric properties in advanced cancer patients. DESIGN: Two quality-of-life
      measurements were performed at baseline and after 7 days. The concurrent validity
      of the European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire - Core 15 - Palliative Care was established by the Pearson
      correlation coefficients with the modified Edmonton Symptom Assessment System,
      the Karnofsky Performance Status and the Brief Pain Inventory - Short Form.
      Reliability was assessed using Cronbach's alpha coefficients and the Spearman
      correlation coefficients of the baseline and of the second measurement of
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire - Core 15 - Palliative Care items. SETTING/PARTICIPANTS: A total of
      160 consecutive patients in one academic palliative medicine centre were
      included. RESULTS: A total of 129 patients completed the study. The concurrent
      validity revealed significant correlations of the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire - Core 15 -
      Palliative Care pain scale with the Brief Pain Inventory - Short Form, the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire - Core 15 - Palliative Care symptom items with the modified
      Edmonton Symptom Assessment System and European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire - Core 15 - Palliative Care
      functional scales with the Karnofsky Performance Status scores. High Cronbach's
      alpha and standardised Cronbach's alpha values were found in the case of both
      functional (range: 0.830-0.925; 0.830-0.932) and symptom scales (range: 0.784
      0.940; 0.794-0.941) of the European Organization for Research and Treatment of
      Cancer Quality of Life Questionnaire - Core 15 - Palliative Care, respectively.
      The Spearman correlation coefficients between the first and the second
      measurements were significant (p < 0.0001) for all European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire - Core 15 -
      Palliative Care items. CONCLUSIONS: Polish version of the European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire - Core 15 -
      Palliative Care is a valid and reliable tool recommended for quality-of-life
      assessment and monitoring in advanced cancer patients.

PMID- 22988043
TI  - Changes over a decade in end-of-life care and transfers during the last 3 months
      of life: a repeated survey among proxies of deceased older people.
AB  - BACKGROUND: In the ageing population, older people are living longer with chronic
      diseases. Especially in the last year of life, this can result in an increased
      need for (complex) end-of-life care. AIM: To study potential changes in received
      end-of-life care and transfers by older people during the last 3 months of life
      between 2000 and 2010. DESIGN: A repeated survey in 2000 and 2010. PARTICIPANTS:
      Data were collected from a sample of proxies of deceased sample members of the
      Longitudinal Aging Study Amsterdam in 2000 (n = 270; response = 79%) and 2010 (n
      = 168; response = 59%). RESULTS: Compared to 2000, in 2010, older people had a
      significantly lower functional ability 3 months before death. Over the 10-year
      period, people were significantly less likely to receive no care (12% vs 39%) and
      more likely to receive formal home care (45% vs 15%). Older people aged over 80
      years, females, and those in the 2010 sample were more likely to receive formal
      home and institutional care (formal home care - age > 80 years, odds ratio: 3.7,
      male odds ratio: 0.74, 2010 - odds ratio: 6.9; institutional care - age > 80
      years, odds ratio: 11.6, male odds ratio: 0.34, 2010 - odds ratio: 2.5) than
      informal or no care. Regardless of the study year, older people receiving
      informal home care were more likely to die in hospital (odds ratio: 2.3).
      CONCLUSION: Two scenarios of care in the last 3 months of life seem to arise:
      staying at home as long as possible with a higher chance of hospital death or
      living in a residential or nursing home, reducing the chance of hospital death.

PMID- 22988042
TI  - Communicating advanced cancer patients' symptoms via the Internet: a pooled
      analysis of two randomized trials examining caregiver preparedness, physical
      burden, and negative mood.
AB  - BACKGROUND: Using available communication technologies, clinicians may offer
      timely support to family caregivers in managing symptoms in patients with
      advanced cancer at home. AIM: To assess the effects of an online symptom
      reporting system on caregiver preparedness, physical burden, and negative mood.
      DESIGN: A pooled analysis of two randomized trials (NCT00214162 and NCT00365963)
      was conducted to compare caregiver outcomes at 6 and 12 months after intervention
      between two randomized, unblinded groups using General Linear Mixed Modeling.
      Caregivers in one group (Comprehensive Health Enhancement Support System-Only)
      were given access to an interactive cancer communication system, the
      Comprehensive Health Enhancement Support System. Those in the other group
      (Comprehensive Health Enhancement Support System + Clinician Report) received
      access to Comprehensive Health Enhancement Support System plus an online symptom
      reporting system called the Clinician Report. Clinicians of patients in the
      Comprehensive Health Enhancement Support System + Clinician Report group received
      e-mail alerts notifying them when a symptom distress was reported over a
      predetermined threshold. SETTING/PARTICIPANTS: Dyads (n = 235) of advanced-stage
      lung, breast, and prostate cancer patients and their adult caregivers were
      recruited at five outpatient oncology clinics in the United States. RESULTS:
      Caregivers in the Comprehensive Health Enhancement Support System + Clinician
      Report group reported less negative mood than those in the Comprehensive Health
      Enhancement Support System-Only group at both 6 months (p = 0.009) and 12 months
      (p = 0.004). Groups were not significantly different on caregiver preparedness or
      physical burden at either time point. CONCLUSIONS: This study provides new
      evidence that by using an online symptom reporting system, caregivers may
      experience less emotional distress due to the Clinician Report's timely
      communication of caregiving needs in symptom management to clinicians.

PMID- 22988044
TI  - Delirium prevalence, incidence, and implications for screening in specialist
      palliative care inpatient settings: a systematic review.
AB  - BACKGROUND: Delirium is a serious neuropsychiatric syndrome frequently
      experienced by palliative care inpatients. This syndrome is under-recognized by
      clinicians. While screening increases recognition, it is not a routine practice.
      AIM AND DESIGN: This systematic review aims to examine methods, quality, and
      results of delirium prevalence and incidence studies in palliative care inpatient
      populations and discuss implications for delirium screening. DATA SOURCES: A
      systematic search of the literature identified prospective studies reporting on
      delirium prevalence and/or incidence in inpatient palliative care adult
      populations from 1980 to 2012. Papers not in English or those reporting the
      occurrence of symptoms not specifically identified as delirium were excluded.
      RESULTS: Of the eight included studies, the majority (98.9%) involved
      participants (1079) with advanced cancer. Eight different screening and
      assessment tools were used. Delirium incidence ranged from 3% to 45%, while
      delirium prevalence varied, with a range of: 13.3%-42.3% at admission, 26%-62%
      during admission, and increasing to 58.8%-88% in the weeks or hours preceding
      death. Studies that used the Diagnostic and Statistical Manual-Fourth Edition
      reported higher prevalence (42%-88%) and incidence (40.2%-45%), while incidence
      rates were higher in studies that screened participants at least daily (32.8%
      45%). Hypoactive delirium was the most prevalent delirium subtype (68%-86% of
      cases). CONCLUSION: The prevalence and incidence of delirium in palliative care
      inpatient settings supports the need for screening. However, there is limited
      consensus on assessment measures or knowledge of implications of delirium
      screening for inpatients and families. Further research is required to develop
      standardized methods of delirium screening, assessment, and management that are
      acceptable to inpatients and families.

PMID- 22988045
TI  - Gait evaluation of the advanced reciprocating gait orthosis with solid versus
      dorsi flexion assist ankle foot orthoses in paraplegic patients.
AB  - BACKGROUND: Mechanical orthoses are used for standing and walking after
      neurological injury. Most orthoses such as the advanced reciprocating gait
      orthosis typically use solid ankle-foot orthoses. OBJECTIVES: The goal of this
      study was to test the effects of ankle dorsiflexion assistance in patients with
      spinal cord injury when ambulating with an advanced reciprocating gait orthosis
      compared to walking with fixed ankles. STUDY DESIGN: Quasi-experimental. METHODS:
      Four patients with spinal cord injury were fitted with an advanced reciprocating
      gait orthosis equipped with solid and dorsiflexion assist-type ankle-foot
      orthoses and walked at their self-selected speed. Joint angles and spatial
      temporal parameters were measured and analyzed. RESULTS: The mean walking speed
      and stride length were both significantly increased along with cadence by the
      volunteer subjects when ambulating using the advanced reciprocating gait orthosis
      fitted with dorsiflexion assist ankle-foot orthoses compared to the advanced
      reciprocating gait orthosis with solid ankle-foot orthoses. The mean ankle joint
      ranges of motion were significantly increased when walking with the advanced
      reciprocating gait orthosis with dorsiflexion assist ankle-foot orthoses compared
      to when using the advanced reciprocating gait orthosis with the solid ankle-foot
      orthoses. Knee joint ranges of motion were reduced, and hip joint ranges of
      motion were increased but not significantly. CONCLUSION: The advanced
      reciprocating gait orthosis fitted with the dorsiflexion assist ankle-foot
      orthoses had the effect of improving gait parameters when compared to the
      advanced reciprocating gait orthosis with solid ankle-foot orthoses. Clinical
      relevance The advanced reciprocating gait orthosis with dorsiflexion assist ankle
      foot orthoses has the potential to improve hip and ankle joint kinematics and the
      temporal-spatial parameters of gait in spinal cord injury patients' walking.

PMID- 22988046
TI  - Sleep apnea and cardiovascular disease: a bidirectional relationship.

PMID- 22988047
TI  - Cardiac magnetic resonance imaging can clearly depict the morphology and
      determine the significance of cor triatriatum.

PMID- 22988048
TI  - Levoatriocardinal vein with partial anomalous venous return and a bidirectional
      shunt.

PMID- 22988049
TI  - Cardiac amyloidosis.

PMID- 22988051
TI  - Letter by khawaja et Al regarding article, "percutaneous coronary intervention in
      patients with severe aortic stenosis: implications for transcatheter aortic valve
      replacement".

PMID- 22988052
TI  - Letter by hendricks regarding article, "obesity and cardiovascular disease".

PMID- 22988053
TI  - Discerning cultural identification from a thinly sliced behavioral sample.
AB  - This research examined whether individual differences in cultural identification
      can be discerned at zero acquaintance. This issue was examined in Hong Kong,
      where the idiosyncrasy of cultural identification is a salient social
      psychological issue. The participants were able to perceive accurately the
      targets' identification with Western culture from a video clip and from a still
      image. Findings also indicated that a stereotype of Western cultural identity
      (i.e., extraversion and particular hairstyle) facilitated these perceptions.
      Specifically, (a) the participants with a stronger stereotype were more accurate
      in perceiving Western cultural identification, (b) the targets who were
      experimentally manipulated to appear extraverted were rated as more strongly
      identifying with Western culture, and (c) the participants relatively unfamiliar
      with these stereotypes did not correctly perceive Western cultural
      identification. Implications of these findings on research on multiculturalism
      are also discussed.

PMID- 22988054
TI  - The cultural construction of self and well-being: a tale of two cities.
AB  - Does local context (e.g., city of residence) matter for self and well-being? We
      theorized that it does because local contexts diverge in prevalent historically
      derived ideas, norms, and products. Through historical analysis, studies of norms
      (tightness-looseness; Study 1) and cultural products (content analyses of
      newspaper headlines, venture capital firm websites, hospital websites; Studies 2
      4), and studies assessing individuals' self and well-being (Studies 5-7), we
      compared Boston and San Francisco-similar cities on many metrics. We find that
      self and well-being are, in some important part, local. Reflecting themes of "old
      and established," Boston's history and cultural products emphasize tradition,
      status, and community, and social norms are relatively tight; accordingly
      feelings and selves are socially contingent. In contrast, reflecting themes of
      "new and free," San Francisco's history and cultural products emphasize unlimited
      possibility, egalitarianism, and innovation, and social norms are relatively
      loose; accordingly feelings and selves are relatively less contingent on others.

PMID- 22988055
TI  - Pediatric phase I trial and pharmacokinetic study of MLN8237, an investigational
      oral selective small-molecule inhibitor of Aurora kinase A: a Children's Oncology
      Group Phase I Consortium study.
AB  - PURPOSE: MLN8237, a selective small-molecule inhibitor of Aurora kinase A, has
      activity in a broad range of preclinical pediatric cancer models. We conducted a
      phase I trial in children with refractory/recurrent solid tumors to define the
      maximum-tolerated dose, toxicities, and pharmacokinetic properties of MLN8237.
      EXPERIMENTAL DESIGN: MLN8237 was administered orally either once daily or divided
      twice daily for seven days, every 21 days. Using a rolling-six design, four dose
      levels (45, 60, 80, and 100 mg/m(2)/day) were evaluated on the once-daily
      schedule, and two dose levels (60 and 80 mg/m(2)/d) on the twice-daily schedule.
      Pharmacokinetic studies were conducted with the initial dose and trough drug
      concentrations also measured at the steady state. RESULTS: Thirty-seven patients
      were enrolled. On the once-daily dosing schedule, myelosuppression was dose
      limiting in three of four patients at 100 mg/m(2), and one of six patients had
      dose-limiting mood alteration at 80 mg/m(2). At 45 mg/m(2), one of six patients
      experienced dose-limiting mucositis. Mucositis and myelosuppression were dose
      limiting at 80 mg/m(2) on the twice-daily schedule, and one of five patients at
      60 mg/m(2) on the twice-daily schedule experienced a dose-limiting alkaline
      phosphatase. Five of 11 patients experienced hand-foot-skin syndrome with twice
      daily dosing versus one of 21 after once-daily dosing. There was one partial
      response and six with prolonged stable disease among 33 evaluable subjects.
      CONCLUSION: The twice-daily dose regimen is well tolerated in adults; however,
      children experienced a greater frequency of myelosuppression and hand-foot-skin
      syndrome on this schedule. Children tolerated a higher dose and the recommended
      pediatric phase II dose is 80 mg/m(2)/d once daily for seven days.

PMID- 22988056
TI  - Stemness of B-cell progenitors in multiple myeloma bone marrow.
AB  - PURPOSE: In myeloma, B cells and plasma cells show a clonal relationship.
      Clonotypic B cells may represent a tumor-initiating compartment or cancer stem
      cell responsible for minimal residual disease in myeloma. EXPERIMENTAL DESIGN: We
      report a study of 58 patients with myeloma at time of diagnosis or relapse. B
      cells in bone marrow were evaluated by multicolor flow cytometry and sorting.
      Clonality was determined by light chain and/or immunoglobulin chain gene
      rearrangement PCR. We also determined aldehyde dehydrogenase activity and colony
      formation growth. Drug sensitivity was tested with conventional and novel agents.
      RESULTS: Marrow CD19+ cells express a light chain identical to plasma cells and
      are therefore termed light chain restricted (LCR). The LCR B-cell mass is small
      in both newly diagnosed and relapsed patients (<= 1%). Few marrow LCR B cells
      (~10%) are CD19+/CD34+, with the rest being more differentiated CD19+/CD34- B
      cells. Marrow LCR CD19+ B cells exhibit enhanced aldehyde dehydrogenase activity
      versus healthy controls. Both CD19+/CD34+ and CD19+/CD34- cells showed colony
      formation activity, with colony growth efficiency optimized when stroma
      conditioned medium was used. B-cell progenitors showed resistance to melphalan,
      lenalidomide, and bortezomib. Panobinostat, a histone deacetylase inhibitor,
      induced apoptosis of LCR B cells and CD138+ cells. LCR B cells are CD117,
      survivin, and Notch positive. CONCLUSIONS: We propose that antigen-independent B
      cell differentiation stages are involved in disease origination and progression
      in myeloma. Furthermore, investigations of myeloma putative stem cell progenitors
      may lead to novel treatments to eradicate the potential reservoir of minimal
      residual disease.

PMID- 22988059
TI  - 90Y Radioembolization after radiation exposure from peptide receptor radionuclide
      therapy.
AB  - Previous radiation therapy of the liver is a contraindication for performing
      (90)Y microsphere radioembolization, and its safety after internal radiation
      exposure through peptide receptor radionuclide therapy (PRRT) has not yet been
      investigated. METHODS: We retrospectively assessed a consecutive cohort of 23
      neuroendocrine tumor (NET) patients with liver-dominant metastatic disease
      undergoing radioembolization with (90)Y microspheres as a salvage therapy after
      failed PRRT. Toxicity was recorded throughout follow-up and reported according to
      Common Terminology Criteria for Adverse Events (version 3). Radiologic (response
      evaluation criteria in solid tumors), biochemical, and symptomatic responses were
      investigated at 3 mo after treatment, and survival analyses were performed with
      the Kaplan-Meier method (log-rank test, P < 0.05). RESULTS: The median follow-up
      period after radioembolization was 38 mo (95% confidence interval, 18-58 mo). The
      mean previous cumulative activity of (177)Lu-DOTA-octreotate was 31.8 GBq. The
      mean cumulative treatment activity of (90)Y microspheres was 3.4 +/- 2.1 GBq,
      administered to the whole liver in a single session (n = 8 patients), in a
      sequential lobar fashion (n = 10 patients), or to only 1 liver lobe (n = 5
      patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded.
      One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall
      response rates for radiologic, biochemical, and symptomatic responses were 30.4%,
      53.8%, and 80%, respectively. The median overall survival was 29 mo (95%
      confidence interval, 4-54 mo) from the first radioembolization session and 54 mo
      (95% confidence interval, 47-61 mo) from the first PRRT cycle. A tumor
      proliferation index Ki-67 greater than 5% predicted shorter survival (P = 0.007).
      CONCLUSION: Radioembolization is a safe and effective salvage treatment option in
      advanced NET patients with liver-dominant tumor burden who failed or reprogressed
      after PRRT. The lack of relevant liver toxicity despite high applied (90)Y
      activities and considerable previous cumulative activities of (177)Lu-octreotate
      is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk
      factor in subsequent radioembolization.

PMID- 22988057
TI  - Immuno-PET of tissue factor in pancreatic cancer.
AB  - Upregulation of tissue factor (TF) expression leads to increased patient
      morbidity and mortality in many solid tumor types. The goal of this study was to
      develop a PET tracer for imaging of TF expression in pancreatic cancer. METHODS:
      ALT-836, a chimeric antihuman TF monoclonal antibody, was conjugated to 2-S-(4
      isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn
      NOTA) and labeled with (64)Cu. To compare the TF binding affinity of ALT-836 and
      NOTA-ALT-836, flow cytometry analysis was performed in 3 pancreatic cancer cell
      lines with different expression levels of TF (from low to high: PANC-1, ASPC-1,
      and BXPC-3). PET, biodistribution, blocking, and histology studies were performed
      on pancreatic tumor-bearing mice to evaluate the ability and specificity of
      (64)Cu-NOTA-ALT-836 to target TF in vivo. RESULTS: There was no difference in TF
      binding affinity between ALT-836 and NOTA-ALT-836. (64)Cu-labeling was achieved
      with high yield and specific activity. Serial PET revealed that the uptake of
      (64)Cu-NOTA-ALT-836 in BXPC-3 tumors (high TF expression) was 5.7 +/- 1.8, 10.4
      +/- 0.8, and 16.5 +/- 2.6 percentage injected dose per gram at 4, 24, and 48 h
      after injection, respectively (n = 4), significantly higher than that in the PANC
      1 and ASPC-1 tumors. Biodistribution data as measured by gamma-counting were
      consistent with the PET findings. Blocking experiments and histology further
      confirmed the TF specificity of (64)Cu-NOTA-ALT-836. CONCLUSION: Herein we report
      the first successful PET imaging of TF expression. Persistent and TF-specific
      uptake of (64)Cu-NOTA-ALT-836 was observed in pancreatic cancer models.

PMID- 22988060
TI  - The interrelationships among paternal and maternal parenting stress, metabolic
      control, and depressive symptoms in adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVE: To examine the relationship between paternal and maternal parenting
      stress, metabolic control, and depressive symptoms in adolescents with type 1
      diabetes mellitus (T1DM). METHODS: 151 adolescents with T1DM (mean age 14.9 +/-
      1.7 years) and a comparison group (n = 122) reported their depressive symptoms
      and behavior problems. Mothers (T1DM n = 126; comparison group n = 106) and
      fathers (T1DM n = 103; comparison group n = 55) each reported parenting stress.
      Metabolic control was assessed by the glycosylated hemoglobin (HbA1c) values
      obtained from the medical records. RESULTS: Fathers of adolescents with T1DM
      reported significantly more parenting stress than fathers of the comparison
      group. Parenting stress was associated with depressive symptoms only in
      adolescents with T1DM. Parenting stress in fathers explained 25% of the variance
      in depressive symptoms in adolescents with T1DM and 18% of the variance in HbA1c.
      In mothers, this was 22% and 19%, respectively. CONCLUSION: The combination of
      blood glucose control and depressive symptoms in adolescents with T1DM was found
      to be associated with both paternal and maternal parenting stress.

PMID- 22988061
TI  - The orally active glutamate carboxypeptidase II inhibitor E2072 exhibits
      sustained nerve exposure and attenuates peripheral neuropathy.
AB  - Peripheral neuropathy from nerve trauma is a significant problem in the human
      population and often constitutes a dose-limiting toxicity in patients receiving
      chemotherapy. (3-2-Mercaptoethyl)biphenyl-2,3-dicarboxylic acid (E2072) is a
      potent (K(i) = 10 nM), selective, and orally available inhibitor of glutamate
      carboxypeptidase II (GCPII). Here, we report that E2072 attenuates hyperalgesia
      and nerve conduction velocity deficits in preclinical rodent models of
      neuropathic pain and oxaliplatin-induced neuropathy. In the chronic constrictive
      injury model, orally administered E2072 reversed pre-existing thermal
      hyperalgesia in rats in a dose-dependent fashion with a minimally effective dose
      of 0.1 mg/kg/day. It is noteworthy that multiple days of dosing of E2072 were
      required before analgesia was realized even though GCPII inhibitory exposures
      were achieved on the first day of dosing. In addition, analgesia was found to
      persist for up to 7 days after cessation of dosing, consistent with E2072's
      pharmacokinetic profile and sustained exposure. Furthermore, in a chronic
      oxaliplatin-induced neuropathy model (6 mg/kg i.p. oxaliplatin twice weekly for 4
      weeks), female BALB/c mice receiving daily oral E2072 at 1.0 and 0.1 mg/kg
      displayed no deficits in either caudal or digital velocity compared with
      significant deficits observed in mice treated with oxaliplatin alone (12 +/- 3
      and 9 +/- 2%, respectively). Similar findings were seen with oxaliplatin-induced
      digital and caudal amplitude deficits. It is noteworthy that E2072 showed no
      interference with the antineoplastic efficacy of oxaliplatin in mice bearing
      leukemia (L1210), even at doses 100 times its neuroprotective/analgesic dose,
      indicating a selective effect on neuropathy. These data support the therapeutic
      utility of GCPII inhibitors in neuropathy and neuropathic pain.

PMID- 22988062
TI  - Inhibitory influence of the hexapeptidic sequence SLIGRL on influenza A virus
      infection in mice.
AB  - Proteinase-activated receptor 2 (PAR(2)) is widely expressed in the respiratory
      tract and is an integral component of the host antimicrobial defense system. The
      principal aim of this study was to investigate the influence of a PAR(2)
      activating peptide, SLIGRL, on influenza A virus (IAV)-induced pathogenesis in
      mice. Intranasal inoculation of BALB/c mice with influenza A/PR/8/34 virus caused
      time-dependent increases in the number of pulmonary leukocytes (recovered from
      bronchoalveolar lavage fluid), marked airway histopathology characterized by
      extensive epithelial cell damage, airway hyper-responsiveness to the
      bronchoconstrictor methacholine, and elevated levels of inflammatory chemokines
      (keratinocyte-derived chemokine and macrophage inflammatory protein 2) and
      cytokines (interferon-gamma). It is noteworthy that these IAV-induced effects
      were dose-dependently attenuated in mice treated with a PAR(2)-activating
      peptide, SLIGRL, at the time of IAV inoculation. However, SLIGRL also inhibited
      IAV-induced increases in pulmonary leukocytes in PAR(2)-deficient mice,
      indicating these antiviral actions were not mediated by PAR(2). The potency order
      obtained for a series of structural analogs of SLIGRL for anti-IAV activity (IGRL
      > SLIGRL > LSIGRL >2-furoyl-LIGRL) was also inconsistent with a PAR(2)-mediated
      effect. In further mechanistic studies, SLIGRL inhibited IAV-induced propagation
      in ex vivo perfused segments of trachea from wild-type or PAR(2)(-/-) mice, but
      did not inhibit viral attachment or replication in Madin-Darby canine kidney
      cells and chorioallantoic membrane cells, which are established hosts for IAV. In
      summary, SLIGRL protected mice from IAV infection independently of PAR(2) and
      independently of direct inhibition of IAV attachment or replication, potentially
      through the activation of endogenous antiviral pathways within the mouse
      respiratory tract.

PMID- 22988063
TI  - Effects of the novel alpha7 nicotinic acetylcholine receptor agonist ABT-107 on
      sensory gating in DBA/2 mice: pharmacodynamic characterization.
AB  - Nicotinic acetylcholine receptor (nAChR) agonists improve sensory gating deficits
      in animal models and schizophrenic patients. The aim of this study was to
      determine whether the novel and selective alpha7 nAChR full agonist 5-(6-[(3R)-1
      azabicyclo[2.2.2]oct-3-yloxy]pyridazin-3-yl)-1H-indole (ABT-107) improves sensory
      gating deficits in DBA/2 mice. Sensory gating was measured by recording
      hippocampal-evoked potential P20-N40 waves and determining gating
      test/conditioning (T/C) ratios in a paired auditory stimulus paradigm. ABT-107 at
      0.1 MUmol/kg (average plasma concentration of 1.1 ng/ml) significantly improved
      sensory gating by lowering T/C ratios during a 30-min period after administration
      in unanesthetized DBA/2 mice. ABT-107 at 1.0 MUmol/kg was ineffective at 30 min
      after administration when average plasma levels were 13.5 ng/ml. However, the 1.0
      MUmol/kg dose was effective 180 min after administration when plasma
      concentration had fallen to 1.9 ng/ml. ABT-107 (0.1 MUmol/kg) also improved
      sensory gating in anesthetized DBA/2 mice pretreated with alpha7 nAChR
      desensitizing doses of nicotine (6.2 MUmol/kg) or ABT-107 (0.1 MUmol/kg) itself.
      Moreover, repeated b.i.d. dosing of ABT-107 (0.1 MUmol/kg) was as efficacious as
      a single dose. The acute efficacy of ABT-107 (0.1 MUmol/kg) was blocked by the
      nAChR antagonist methyllycaconitine, but not by the alpha4beta2 nAChR antagonist
      dihydro-beta-erythroidine. These studies demonstrate that ABT-107 improves
      sensory gating through the activation of nAChRs, and efficacy is sustained under
      conditions of repeated dosing or with prior nAChR activation with nicotine.

PMID- 22988064
TI  - Engineering a model protein cavity to catalyze the Kemp elimination.
AB  - Synthetic cavitands and protein cavities have been widely studied as models for
      ligand recognition. Here we investigate the Met102 -> His substitution in the
      artificial L99A cavity in T4 lysozyme as a Kemp eliminase. The resulting enzyme
      had k(cat)/K(M) = 0.43 M(-1) s(-1) and a (k(cat)/K(M))/k(uncat) = 10(7) at pH
      5.0. The crystal structure of this enzyme was determined at 1.30 A, as were the
      structures of four complexes of substrate and product analogs. The absence of
      ordered waters or hydrogen bonding interactions, and the presence of a common
      catalytic base (His102) in an otherwise hydrophobic, buried cavity, facilitated
      detailed analysis of the reaction mechanism and its optimization. Subsequent
      substitutions increased eliminase activity by an additional four-fold. As
      activity-enhancing substitutions were engineered into the cavity, protein
      stability decreased, consistent with the stability-function trade-off hypothesis.
      This and related model cavities may provide templates for studying protein design
      principles in radically simplified environments.

PMID- 22988065
TI  - Statistical inference of the generation probability of T-cell receptors from
      sequence repertoires.
AB  - Stochastic rearrangement of germline V-, D-, and J-genes to create variable
      coding sequence for certain cell surface receptors is at the origin of immune
      system diversity. This process, known as "VDJ recombination", is implemented via
      a series of stochastic molecular events involving gene choices and random
      nucleotide insertions between, and deletions from, genes. We use large sequence
      repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains
      to infer the statistical properties of these basic biochemical events. Because
      any given CDR3 sequence can be produced in multiple ways, the probability
      distribution of hidden recombination events cannot be inferred directly from the
      observed sequences; we therefore develop a maximum likelihood inference method to
      achieve this end. To separate the properties of the molecular rearrangement
      mechanism from the effects of selection, we focus on nonproductive CDR3 sequences
      in T-cell DNA. We infer the joint distribution of the various generative events
      that occur when a new T-cell receptor gene is created. We find a rich picture of
      correlation (and absence thereof), providing insight into the molecular
      mechanisms involved. The generative event statistics are consistent between
      individuals, suggesting a universal biochemical process. Our probabilistic model
      predicts the generation probability of any specific CDR3 sequence by the
      primitive recombination process, allowing us to quantify the potential diversity
      of the T-cell repertoire and to understand why some sequences are shared between
      individuals. We argue that the use of formal statistical inference methods, of
      the kind presented in this paper, will be essential for quantitative
      understanding of the generation and evolution of diversity in the adaptive immune
      system.

PMID- 22988066
TI  - Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation.
AB  - Intrinsically disordered proteins (IDP) are a broad class of proteins with
      relatively flat energy landscapes showing a high level of functional promiscuity,
      which are frequently regulated through posttranslational covalent modifications.
      Histone tails, which are the terminal segments of the histone proteins, are
      prominent IDPs that are implicated in a variety of signaling processes, which
      control chromatin organization and dynamics. Although a large body of work has
      been done on elucidating the roles of posttranslational modifications in
      functional regulation of IDPs, molecular mechanisms behind the observed behaviors
      are not fully understood. Using extensive atomistic molecular dynamics
      simulations, we found in this work that H4 tail mono-acetylation at LYS-16, which
      is a key covalent modification, induces a significant reorganization of the
      tail's conformational landscape, inducing partial ordering and enhancing the
      propensity for alpha-helical segments. Furthermore, our calculations of the
      potentials of mean force between the H4 tail and a DNA fragment indicate that
      contrary to the expectations based on simple electrostatic reasoning, the Lys-16
      mono-acetylated H4 tail binds to DNA stronger than the unacetylated protein.
      Based on these results, we propose a molecular mechanism for the way Lys-16
      acetylation might lead to experimentally observed disruption of compact chromatin
      fibers.

PMID- 22988067
TI  - Role of isostaticity and load-bearing microstructure in the elasticity of yielded
      colloidal gels.
AB  - We report a simple correlation between microstructure and strain-dependent
      elasticity in colloidal gels by visualizing the evolution of cluster structure in
      high strain-rate flows. We control the initial gel microstructure by inducing
      different levels of isotropic depletion attraction between particles suspended in
      refractive index matched solvents. Contrary to previous ideas from mode coupling
      and micromechanical treatments, our studies show that bond breakage occurs mainly
      due to the erosion of rigid clusters that persist far beyond the yield strain.
      This rigidity contributes to gel elasticity even when the sample is fully
      fluidized; the origin of the elasticity is the slow Brownian relaxation of rigid,
      hydrodynamically interacting clusters. We find a power-law scaling of the elastic
      modulus with the stress-bearing volume fraction that is valid over a range of
      volume fractions and gelation conditions. These results provide a conceptual
      framework to quantitatively connect the flow-induced microstructure of soft
      materials to their nonlinear rheology.

PMID- 22988069
TI  - Unprecedented hydroxyl radical-dependent two-step chemiluminescence production by
      polyhalogenated quinoid carcinogens and H2O2.
AB  - Most chemiluminescence (CL) reactions usually generate only one-step CL, which is
      rarely dependent on the highly reactive and biologically/environmentally
      important hydroxyl radicals ((*)OH). Here, we show that an unprecedented two-step
      CL can be produced by the carcinogenic tetrachloro-1,4-benzoquinone (also known
      as p-chloranil) and H(2)O(2), which was found to be well-correlated to and
      directly dependent on its two-step metal-independent production of (*)OH. We
      proposed that (*)OH-dependent formation of quinone-dioxetane and electronically
      excited carbonyl species might be responsible for this unusual two-step CL
      production by tetrachloro-1,4-benzoquinone/H(2)O(2). This is a unique report of a
      previously undefined two-step CL-producing system that is dependent on
      intrinsically formed (*)OH. These findings may have potential applications in
      detecting and quantifying (*)OH and the ubiquitous polyhalogenated aromatic
      carcinogens, which may have broad biological and environmental implications for
      future research on these types of important species.

PMID- 22988070
TI  - On the strength of glasses.
AB  - The remarkable strength of glasses is examined using the random first order
      transition theory of the glass transition. The theory predicts that strength
      depends on elastic modulus but also on the configurational energy frozen in when
      the glass is prepared. The stress catalysis of cooperative rearrangements of the
      type responsible for the supercooled liquid's high viscosity account
      quantitatively for the measured strength of a range of metallic glasses, silica,
      and a polymer glass.

PMID- 22988071
TI  - Independent evaluation of conflicting microspherule results from different
      investigations of the Younger Dryas impact hypothesis.
AB  - Firestone et al. sampled sedimentary sequences at many sites across North
      America, Europe, and Asia [Firestone RB, et al. (2007) Proc Natl Acad Sci USA
      106:16016-16021]. In sediments dated to the Younger Dryas onset or Boundary (YDB)
      approximately 12,900 calendar years ago, Firestone et al. reported discovery of
      markers, including nanodiamonds, aciniform soot, high-temperature melt-glass, and
      magnetic microspherules attributed to cosmic impacts/airbursts. The
      microspherules were explained as either cosmic material ablation or terrestrial
      ejecta from a hypothesized North American impact that initiated the abrupt
      Younger Dryas cooling, contributed to megafaunal extinctions, and triggered human
      cultural shifts and population declines. A number of independent groups have
      confirmed the presence of YDB spherules, but two have not. One of them [Surovell
      TA, et al. (2009) Proc Natl Acad Sci USA 104:18155-18158] collected and analyzed
      samples from seven YDB sites, purportedly using the same protocol as Firestone et
      al., but did not find a single spherule in YDB sediments at two previously
      reported sites. To examine this discrepancy, we conducted an independent blind
      investigation of two sites common to both studies, and a third site investigated
      only by Surovell et al. We found abundant YDB microspherules at all three widely
      separated sites consistent with the results of Firestone et al. and conclude that
      the analytical protocol employed by Surovell et al. deviated significantly from
      that of Firestone et al. Morphological and geochemical analyses of YDB spherules
      suggest they are not cosmic, volcanic, authigenic, or anthropogenic in origin.
      Instead, they appear to have formed from abrupt melting and quenching of
      terrestrial materials.

PMID- 22988072
TI  - Complexity of chromatin folding is captured by the strings and binders switch
      model.
AB  - Chromatin has a complex spatial organization in the cell nucleus that serves
      vital functional purposes. A variety of chromatin folding conformations has been
      detected by single-cell imaging and chromosome conformation capture-based
      approaches. However, a unified quantitative framework describing spatial
      chromatin organization is still lacking. Here, we explore the "strings and
      binders switch" model to explain the origin and variety of chromatin behaviors
      that coexist and dynamically change within living cells. This simple polymer
      model recapitulates the scaling properties of chromatin folding reported
      experimentally in different cellular systems, the fractal state of chromatin, the
      processes of domain formation, and looping out. Additionally, the strings and
      binders switch model reproduces the recently proposed "fractal-globule" model,
      but only as one of many possible transient conformations.

PMID- 22988073
TI  - Programmed -1 frameshifting efficiency correlates with RNA pseudoknot
      conformational plasticity, not resistance to mechanical unfolding.
AB  - Programmed -1 frameshifting, whereby the reading frame of a ribosome on messenger
      RNA is shifted in order to generate an alternate gene product, is often triggered
      by a pseudoknot structure in the mRNA in combination with an upstream slippery
      sequence. The efficiency of frameshifting varies widely for different sites, but
      the factors that determine frameshifting efficiency are not yet fully understood.
      Previous work has suggested that frameshifting efficiency is related to the
      resistance of the pseudoknot against mechanical unfolding. We tested this
      hypothesis by studying the mechanical properties of a panel of pseudoknots with
      frameshifting efficiencies ranging from 2% to 30%: four pseudoknots from
      retroviruses, two from luteoviruses, one from a coronavirus, and a
      nonframeshifting bacteriophage pseudoknot. Using optical tweezers to apply
      tension across the RNA, we measured the distribution of forces required to unfold
      each pseudoknot. We found that neither the average unfolding force, nor the
      unfolding kinetics, nor the parameters describing the energy landscape for
      mechanical unfolding of the pseudoknot (energy barrier height and distance to the
      transition state) could be correlated to frameshifting efficiency. These results
      indicate that the resistance of pseudoknots to mechanical unfolding is not a
      primary determinant of frameshifting efficiency. However, increased frameshifting
      efficiency was correlated with an increased tendency to form alternate,
      incompletely folded structures, suggesting a more complex picture of the role of
      the pseudoknot involving the conformational dynamics.

PMID- 22988074
TI  - Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide.
AB  - Gene regulation by DNA binding small molecules could have important therapeutic
      applications. This study reports the investigation of a DNA-binding pyrrole
      imidazole polyamide targeted to bind the DNA sequence 5'-WGGWWW-3' with reference
      to its potency in a subcutaneous xenograft tumor model. The molecule is capable
      of trafficking to the tumor site following subcutaneous injection and modulates
      transcription of select genes in vivo. An FITC-labeled analogue of this polyamide
      can be detected in tumor-derived cells by confocal microscopy. RNA deep
      sequencing (RNA-seq) of tumor tissue allowed the identification of further
      affected genes, a representative panel of which was interrogated by quantitative
      reverse transcription-PCR and correlated with cell culture expression levels.

PMID- 22988078
TI  - Dynamics of the last glacial maximum Antarctic ice-sheet and its response to
      ocean forcing.
AB  - Retreat of the Last Glacial Maximum (LGM) Antarctic ice sheet is thought to have
      been initiated by changes in ocean heat and eustatic sea level propagated from
      the Northern Hemisphere (NH) as northern ice sheets melted under rising
      atmospheric temperatures. The extent to which spatial variability in ice dynamics
      may have modulated the resultant pattern and timing of decay of the Antarctic ice
      sheet has so far received little attention, however, despite the growing
      recognition that dynamic effects account for a sizeable proportion of mass
      balance changes observed in modern ice sheets. Here we use a 5-km resolution
      whole-continent numerical ice-sheet model to assess whether differences in the
      mechanisms governing ice sheet flow could account for discrepancies between
      geochronological studies in different parts of the continent. We first simulate
      the geometry and flow characteristics of an equilibrium LGM ice sheet, using pan
      Antarctic terrestrial and marine geological data for constraint, then perturb the
      system with sea level and ocean heat flux increases to investigate ice-sheet
      vulnerability. Our results identify that fast-flowing glaciers in the eastern
      Weddell Sea, the Amundsen Sea, central Ross Sea, and in the Amery Trough respond
      most rapidly to ocean forcings, in agreement with empirical data. Most
      significantly, we find that although ocean warming and sea-level rise bring about
      mainly localized glacier acceleration, concomitant drawdown of ice from
      neighboring areas leads to widespread thinning of entire glacier catchments-a
      discovery that has important ramifications for the dynamic changes presently
      being observed in modern ice sheets.

PMID- 22988076
TI  - High-throughput lensfree 3D tracking of human sperms reveals rare statistics of
      helical trajectories.
AB  - Dynamic tracking of human sperms across a large volume is a challenging task. To
      provide a high-throughput solution to this important need, here we describe a
      lensfree on-chip imaging technique that can track the three-dimensional (3D)
      trajectories of > 1,500 individual human sperms within an observation volume of
      approximately 8-17 mm(3). This computational imaging platform relies on
      holographic lensfree shadows of sperms that are simultaneously acquired at two
      different wavelengths, emanating from two partially-coherent sources that are
      placed at 45 degrees  with respect to each other. This multiangle and multicolor
      illumination scheme permits us to dynamically track the 3D motion of human sperms
      across a field-of-view of > 17 mm(2) and depth-of-field of approximately 0.5-1 mm
      with submicron positioning accuracy. The large statistics provided by this
      lensfree imaging platform revealed that only approximately 4-5% of the motile
      human sperms swim along well-defined helices and that this percentage can be
      significantly suppressed under seminal plasma. Furthermore, among these observed
      helical human sperms, a significant majority (approximately 90%) preferred right
      handed helices over left-handed ones, with a helix radius of approximately 0.5-3
      MUm, a helical rotation speed of approximately 3-20 rotations/s and a linear
      speed of approximately 20-100 MUm/s. This high-throughput 3D imaging platform
      could in general be quite valuable for observing the statistical swimming
      patterns of various other microorganisms, leading to new insights in their 3D
      motion and the underlying biophysics.

PMID- 22988079
TI  - Multi-scale kinetics of a field-directed colloidal phase transition.
AB  - Polarizable colloids are expected to form crystalline equilibrium phases when
      exposed to a steady, uniform field. However, when colloids become localized this
      field-induced phase transition arrests and the suspension persists indefinitely
      as a kinetically trapped, percolated structure. We anneal such gels formed from
      magneto-rheological fluids by toggling the field strength at varied frequencies.
      This processing allows the arrested structure to relax periodically to
      equilibrium--colloid-rich, cylindrical columns. Two distinct growth regimes are
      observed: one in which particle domains ripen through diffusive relaxation of the
      gel, and the other where the system-spanning structure collapses and columnar
      domains coalesce apparently through field-driven interactions. There is a stark
      boundary as a function of magnetic field strength and toggle frequency
      distinguishing the two regimes. These results demonstrate how kinetic barriers to
      a colloidal phase transition are subverted through measured, periodic variation
      of driving forces. Such directed assembly may be harnessed to create unique
      materials from dispersions of colloids.

PMID- 22988080
TI  - Alternating electron and proton transfer steps in photosynthetic water oxidation.
AB  - Water oxidation by cyanobacteria, algae, and plants is pivotal in oxygenic
      photosynthesis, the process that powers life on Earth, and is the paradigm for
      engineering solar fuel-production systems. Each complete reaction cycle of
      photosynthetic water oxidation requires the removal of four electrons and four
      protons from the catalytic site, a manganese-calcium complex and its protein
      environment in photosystem II. In time-resolved photothermal beam deflection
      experiments, we monitored apparent volume changes of the photosystem II protein
      associated with charge creation by light-induced electron transfer (contraction)
      and charge-compensating proton relocation (expansion). Two previously invisible
      proton removal steps were detected, thereby filling two gaps in the basic
      reaction-cycle model of photosynthetic water oxidation. In the S(2) -> S(3)
      transition of the classical S-state cycle, an intermediate is formed by
      deprotonation clearly before electron transfer to the oxidant (Y Z OX). The rate
      determining elementary step (tau, approximately 30 us at 20  degrees C) in the
      long-distance proton relocation toward the protein-water interface is
      characterized by a high activation energy (E(a) = 0.46 +/- 0.05 eV) and strong
      H/D kinetic isotope effect (approximately 6). The characteristics of a proton
      transfer step during the S(0) -> S(1) transition are similar (tau, approximately
      100 us; E(a) = 0.34 +/- 0.08 eV; kinetic isotope effect, approximately 3);
      however, the proton removal from the Mn complex proceeds after electron transfer
      to . By discovery of the transient formation of two further intermediate states
      in the reaction cycle of photosynthetic water oxidation, a temporal sequence of
      strictly alternating removal of electrons and protons from the catalytic site is
      established.

PMID- 22988081
TI  - Synthesis of site-specific antibody-drug conjugates using unnatural amino acids.
AB  - Antibody-drug conjugates (ADCs) allow selective targeting of cytotoxic drugs to
      cancer cells presenting tumor-associated surface markers, thereby minimizing
      systemic toxicity. Traditionally, the drug is conjugated nonselectively to
      cysteine or lysine residues in the antibody. However, these strategies often lead
      to heterogeneous products, which make optimization of the biological, physical,
      and pharmacological properties of an ADC challenging. Here we demonstrate the use
      of genetically encoded unnatural amino acids with orthogonal chemical reactivity
      to synthesize homogeneous ADCs with precise control of conjugation site and
      stoichiometry. p-Acetylphenylalanine was site-specifically incorporated into an
      anti-Her2 antibody Fab fragment and full-length IgG in Escherichia coli and
      mammalian cells, respectively. The mutant protein was selectively and efficiently
      conjugated to an auristatin derivative through a stable oxime linkage. The
      resulting conjugates demonstrated excellent pharmacokinetics, potent in vitro
      cytotoxic activity against Her2(+) cancer cells, and complete tumor regression in
      rodent xenograft treatment models. The synthesis and characterization of
      homogeneous ADCs with medicinal chemistry-like control over macromolecular
      structure should facilitate the optimization of ADCs for a host of therapeutic
      uses.

PMID- 22988082
TI  - Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from
      reinfection via epigenetic reprogramming of monocytes.
AB  - Adaptive features of innate immunity, recently described as "trained immunity,"
      have been documented in plants, invertebrate animals, and mice, but not yet in
      humans. Here we show that bacille Calmette-Guerin (BCG) vaccination in healthy
      volunteers led not only to a four- to sevenfold increase in the production of IFN
      gamma, but also to a twofold enhanced release of monocyte-derived cytokines, such
      as TNF and IL-1beta, in response to unrelated bacterial and fungal pathogens. The
      enhanced function of circulating monocytes persisted for at least 3 mo after
      vaccination and was accompanied by increased expression of activation markers
      such as CD11b and Toll-like receptor 4. These training effects were induced
      through the NOD2 receptor and mediated by increased histone 3 lysine 4
      trimethylation. In experimental studies, BCG vaccination induced T- and B
      lymphocyte-independent protection of severe combined immunodeficiency SCID mice
      from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in
      control mice). In conclusion, BCG induces trained immunity and nonspecific
      protection from infections through epigenetic reprogramming of innate immune
      cells.

PMID- 22988083
TI  - Hemisphere-scale differences in conifer evolutionary dynamics.
AB  - Fundamental differences in the distribution of oceans and landmasses in the
      Northern and Southern Hemispheres potentially impact patterns of biological
      diversity in the two areas. The evolutionary history of conifers provides an
      opportunity to explore these dynamics, because the majority of extant conifer
      species belong to lineages that have been broadly confined to the Northern or
      Southern Hemisphere during the Cenozoic. Incorporating genetic information with a
      critical review of fossil evidence, we developed an age-calibrated phylogeny
      sampling ~80% of living conifer species. Most extant conifer species diverged
      recently during the Neogene within clades that generally were established during
      the later Mesozoic, but lineages that diversified mainly in the Southern
      Hemisphere show a significantly older distribution of divergence ages than their
      counterparts in the Northern Hemisphere. Our tree topology and divergence times
      also are best fit by diversification models in which Northern Hemisphere conifer
      lineages have higher rates of species turnover than Southern Hemisphere lineages.
      The abundance of recent divergences in northern clades may reflect complex
      patterns of migration and range shifts during climatic cycles over the later
      Neogene leading to elevated rates of speciation and extinction, whereas the
      scattered persistence of mild, wetter habitats in the Southern Hemisphere may
      have favored the survival of older lineages.

PMID- 22988084
TI  - The widely used small subunit 18S rDNA molecule greatly underestimates true
      diversity in biodiversity surveys of the meiofauna.
AB  - Molecular tools have revolutionized the exploration of biodiversity, especially
      in organisms for which traditional taxonomy is difficult, such as for microscopic
      animals (meiofauna). Environmental (eDNA) metabarcode surveys of DNA extracted
      from sediment samples are increasingly popular for surveying biodiversity. Most
      eDNA surveys use the nuclear gene-encoding small-subunit rDNA gene (18S) as a
      marker; however, different markers and metrics used for delimiting species have
      not yet been evaluated against each other or against morphologically defined
      species (morphospecies). We assessed more than 12,000 meiofaunal sequences of 18S
      and of the main alternatively used marker [Cytochrome c oxidase subunit I (COI)
      mtDNA] belonging to 55 datasets covering three taxonomic ranks. Our results show
      that 18S reduced diversity estimates by a factor of 0.4 relative to
      morphospecies, whereas COI increased diversity estimates by a factor of 7.6.
      Moreover, estimates of species richness using COI were robust among three of four
      commonly used delimitation metrics, whereas estimates using 18S varied widely
      with the different metrics. We show that meiofaunal diversity has been greatly
      underestimated by 18S eDNA surveys and that the use of COI provides a better
      estimate of diversity. The suitability of COI is supported by cross-mating
      experiments in the literature and evolutionary analyses of discreteness in
      patterns of genetic variation. Furthermore its splitting of morphospecies is
      expected from documented levels of cryptic taxa in exemplar meiofauna. We
      recommend against using 18S as a marker for biodiversity surveys and suggest that
      use of COI for eDNA surveys could provide more accurate estimates of species
      richness in the future.

PMID- 22988085
TI  - Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory
      pseudosubstrate.
AB  - The type II p21-activated kinases (PAKs) are key effectors of RHO-family GTPases
      involved in cell motility, survival, and proliferation. Using a structure-guided
      approach, we discovered that type II PAKs are regulated by an N-terminal
      autoinhibitory pseudosubstrate motif centered on a critical proline residue, and
      that this regulation occurs independently of activation loop phosphorylation. We
      determined six X-ray crystal structures of either full-length PAK4 or its
      catalytic domain, that demonstrate the molecular basis for pseudosubstrate
      binding to the active state with phosphorylated activation loop. We show that
      full-length PAK4 is constitutively autoinhibited, but mutation of the
      pseudosubstrate releases this inhibition and causes increased phosphorylation of
      the apoptotic regulation protein Bcl-2/Bcl-X(L) antagonist causing cell death and
      cellular morphological changes. We also find that PAK6 is regulated by the
      pseudosubstrate region, indicating a common type II PAK autoregulatory mechanism.
      Finally, we find Src SH3, but not beta-PIX SH3, can activate PAK4. We provide a
      unique understanding for type II PAK regulation.

PMID- 22988086
TI  - Global forecasts of urban expansion to 2030 and direct impacts on biodiversity
      and carbon pools.
AB  - Urban land-cover change threatens biodiversity and affects ecosystem productivity
      through loss of habitat, biomass, and carbon storage. However, despite
      projections that world urban populations will increase to nearly 5 billion by
      2030, little is known about future locations, magnitudes, and rates of urban
      expansion. Here we develop spatially explicit probabilistic forecasts of global
      urban land-cover change and explore the direct impacts on biodiversity hotspots
      and tropical carbon biomass. If current trends in population density continue and
      all areas with high probabilities of urban expansion undergo change, then by
      2030, urban land cover will increase by 1.2 million km(2), nearly tripling the
      global urban land area circa 2000. This increase would result in considerable
      loss of habitats in key biodiversity hotspots, with the highest rates of
      forecasted urban growth to take place in regions that were relatively undisturbed
      by urban development in 2000: the Eastern Afromontane, the Guinean Forests of
      West Africa, and the Western Ghats and Sri Lanka hotspots. Within the pan
      tropics, loss in vegetation biomass from areas with high probability of urban
      expansion is estimated to be 1.38 PgC (0.05 PgC yr(-1)), equal to ~5% of
      emissions from tropical deforestation and land-use change. Although urbanization
      is often considered a local issue, the aggregate global impacts of projected
      urban expansion will require significant policy changes to affect future growth
      trajectories to minimize global biodiversity and vegetation carbon losses.

PMID- 22988087
TI  - Small RNA binding-site multiplicity involved in translational regulation of a
      polycistronic mRNA.
AB  - In animal systems, mRNAs subject to posttranscriptional regulation by small RNAs
      (sRNAs) often possess multiple binding sites with imperfect complementarity to a
      given sRNA. In contrast, small RNA-mRNA interactions in bacteria and plants
      typically involve a single binding site. In a previous study, we demonstrated
      that the Escherichia coli sRNA SgrS base pairs with a site in the coding region
      of the first gene of a polycistronic message, manXYZ. This interaction was shown
      to be responsible for translational repression of manX and to contribute to
      destabilization of the manXYZ mRNA. In the current study, we report that
      translational repression of the manY and manZ genes by SgrS requires a second
      binding site located in the manX-manY intergenic region. Pairing at this site can
      repress translation of manY and manZ even when mRNA degradation is blocked. Base
      pairing between SgrS and the manX site does not affect translation of manY or
      manZ. Pairing at both sites is required for optimal SgrS-mediated degradation of
      the full-length manXYZ mRNA and for a particular stress phenotype. These results
      suggest that bacterial sRNAs may use target-site multiplicity to enhance the
      efficiency and stringency of regulation. Moreover, use of multiple binding sites
      may be particularly important for coordinating regulation of multiple genes
      encoded in operons.

PMID- 22988088
TI  - Platelet biogenesis and functions require correct protein O-glycosylation.
AB  - Platelets express a variety of membrane and secreted glycoproteins, but the
      importance of glycosylation to platelet functions is poorly understood. To
      explore the importance of O-glycosylation, we generated mice with a targeted
      deletion of Cosmc in murine endothelial/hematopoietic cells (EHC) (EHC Cosmc(
      /y)). X-linked Cosmc encodes an essential chaperone that regulates protein O
      glycosylation. This targeted mutation resulted in lethal perinatal hemorrhage in
      the majority of mice, and the surviving mice displayed severely prolonged tail
      bleeding times and macrothrombocytopenia. EHC Cosmc(-/y) platelets exhibited a
      marked decrease in GPIb-IX-V function and agonist-mediated integrin alphaIIbbeta3
      activation, associated with loss of interactions with von Willebrand factor and
      fibrinogen, respectively. Significantly, three O-glycosylated glycoproteins,
      GPIbalpha, alphaIIb, and GPVI normally on platelet surfaces that play essential
      roles in platelet functions, were partially proteolyzed in EHC Cosmc(-/y)
      platelets. These results demonstrate that extended O-glycans are required for
      normal biogenesis of the platelets as well as the expression and functions of
      their essential glycoproteins, and that variations in O-glycosylation may
      contribute to altered hemostasis.

PMID- 22988089
TI  - Prolonging the postcomplex spike pause speeds eyeblink conditioning.
AB  - Climbing fiber input to the cerebellum is believed to serve as a teaching signal
      during associative, cerebellum-dependent forms of motor learning. However, it is
      not understood how this neural pathway coordinates changes in cerebellar
      circuitry during learning. Here, we use pharmacological manipulations to prolong
      the postcomplex spike pause, a component of the climbing fiber signal in Purkinje
      neurons, and show that these manipulations enhance the rate of learning in
      classical eyelid conditioning. Our findings elucidate an unappreciated aspect of
      the climbing fiber teaching signal, and are consistent with a model in which
      convergent postcomplex spike pauses drive learning-related plasticity in the deep
      cerebellar nucleus. They also suggest a physiological mechanism that could
      modulate motor learning rates.

PMID- 22988090
TI  - Integration of stress-related and reactive oxygen species-mediated signals by
      Topoisomerase VI in Arabidopsis thaliana.
AB  - Environmental stress often leads to an increased production of reactive oxygen
      species that are involved in plastid-to-nucleus retrograde signaling. Soon after
      the release of singlet oxygen ((1)O(2)) in chloroplasts of the flu mutant of
      Arabidopsis, reprogramming of nuclear gene expression reveals a rapid transfer of
      signals from the plastid to the nucleus. We have identified extraplastidic
      signaling constituents involved in (1)O(2)-initiated plastid-to-nucleus signaling
      and nuclear gene activation after mutagenizing a flu line expressing the
      luciferase reporter gene under the control of the promoter of a (1)O(2)
      responsive AAA-ATPase gene (At3g28580) and isolating second-site mutations that
      lead to a constitutive up-regulation of the reporter gene or abrogate its (1)O(2)
      dependent up-regulation. One of these mutants, caa39, turned out to be a weak
      mutant allele of the Topoisomerase VI (Topo VI) A-subunit gene with a single
      amino acid substitution. Transcript profile analysis of flu and flu caa39 mutants
      revealed that Topo VI is necessary for the full activation of AAA-ATPase and a
      set of (1)O(2)-responsive transcripts in response to (1)O(2). Topo VI binds to
      the promoter of the AAA-ATPase and other (1)O(2)-responsive genes, and hence
      could directly regulate their expression. Under photoinhibitory stress
      conditions, which enhance the production of (1)O(2) and H(2)O(2), Topo VI
      regulates (1)O(2)-responsive and H(2)O(2)-responsive genes in a distinct manner.
      These results suggest that Topo VI acts as an integrator of multiple signals
      generated by reactive oxygen species formed in plants under adverse environmental
      conditions.

PMID- 22988091
TI  - Discovery of an orally active small-molecule irreversible inhibitor of protein
      disulfide isomerase for ovarian cancer treatment.
AB  - Protein disulfide isomerase (PDI), an endoplasmic reticulum chaperone protein,
      catalyzes disulfide bond breakage, formation, and rearrangement. The effect of
      PDI inhibition on ovarian cancer progression is not yet clear, and there is a
      need for potent, selective, and safe small-molecule inhibitors of PDI. Here, we
      report a class of propynoic acid carbamoyl methyl amides (PACMAs) that are active
      against a panel of human ovarian cancer cell lines. Using fluorescent
      derivatives, 2D gel electrophoresis, and MS, we established that PACMA 31, one of
      the most active analogs, acts as an irreversible small-molecule inhibitor of PDI,
      forming a covalent bond with the active site cysteines of PDI. We also showed
      that PDI activity is essential for the survival and proliferation of human
      ovarian cancer cells. In vivo, PACMA 31 showed tumor targeting ability and
      significantly suppressed ovarian tumor growth without causing toxicity to normal
      tissues. These irreversible small-molecule PDI inhibitors represent an important
      approach for the development of targeted anticancer agents for ovarian cancer
      therapy, and they can also serve as useful probes for investigating the biology
      of PDI-implicated pathways.

PMID- 22988092
TI  - Altered fear learning across development in both mouse and human.
AB  - The only evidence-based behavioral treatment for anxiety and stress-related
      disorders involves desensitization techniques that rely on principles of
      extinction learning. However, 40% of patients do not respond to this treatment.
      Efforts have focused on individual differences in treatment response, but have
      not examined when, during development, such treatments may be most effective. We
      examined fear-extinction learning across development in mice and humans. Parallel
      behavioral studies revealed attenuated extinction learning during adolescence.
      Probing neural circuitry in mice revealed altered synaptic plasticity of
      prefrontal cortical regions implicated in suppression of fear responses across
      development. The results suggest a lack of synaptic plasticity in the prefrontal
      regions, during adolescence, is associated with blunted regulation of fear
      extinction. These findings provide insight into optimizing treatment outcomes for
      when, during development, exposure therapies may be most effective.

PMID- 22988093
TI  - Selective requirement for Mediator MED23 in Ras-active lung cancer.
AB  - K-RAS-activating mutations occur frequently in non-small cell lung cancer,
      leading to aberrant activation of the Ras-MAPK signaling pathway that contributes
      to the malignant phenotype. However, the development of Ras-targeted therapeutics
      remains challenging. Here, we show that MED23, a component of the multisubunit
      Mediator complex that is known to integrate signaling and gene activities, is
      selectively important for Ras-active lung cancer. By screening a large panel of
      human lung cancer cell lines with or without a Ras mutation, we found that Med23
      RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer
      cells with hyperactive Ras activity. Med23 deficiency in fibroblasts selectively
      inhibited the oncogenic transformation induced by Ras but not by c-Myc. The
      transcription factor ELK1, which is phosphorylated by MAPK for relaying Ras
      signaling to MED23, also was required for the Ras-driven oncogenesis.
      Transcriptome analysis revealed that MED23 and ELK1 co-regulate a common set of
      target genes enriched in regulating cell-cycle and -proliferation functions to
      support the Ras dependency. Furthermore, MED23 was up-regulated by Ras
      transformation in correlation with the strength of Ras signaling as indicated by
      the ELK1 phosphorylation level and was found to be overexpressed in both Ras
      mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23
      expression predicted better survival in Ras-active lung cancer patients and
      xenograft mice. Collectively, our findings demonstrate a critical role for MED23
      in enabling the "Ras-addiction" of lung carcinogenesis, thus providing a
      vulnerable target for the treatment of Ras-active lung cancer.

PMID- 22988094
TI  - Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and
      humoral immune responses.
AB  - IgM antibodies have been known for decades to enhance humoral immune responses in
      an antigen-specific fashion. This enhancement has been thought to be dependent on
      complement activation by IgM-antigen complexes; however, recent genetic studies
      render this mechanism unlikely. Here, we describe a likely alternative
      explanation; mice lacking the recently identified Fc receptor for IgM (FcMUR) on
      B cells produced significantly less antibody to protein antigen during both
      primary and memory responses. This immune deficiency was accompanied by impaired
      germinal center formation and decreased plasma and memory B-cell generation.
      FcMUR did not affect steady-state B-cell survival but specifically enhanced the
      survival and proliferation induced by B-cell receptor cross-linking. Moreover,
      FcMUR-deficient mice produced far more autoantibodies than control mice as they
      aged, suggesting that FcMUR is also required for maintaining tolerance to self
      antigens. Our results thus define a unique pathway mediated by the FcMUR for
      regulating immunity and tolerance and suggest that IgM antibodies promote humoral
      immune responses to foreign antigen yet suppress autoantibody production through
      at least two pathways: complement activation and FcMUR.

PMID- 22988095
TI  - O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models
      of human neurodegenerative diseases.
AB  - O-GlcNAcylation is an abundant posttranslational modification in the brain
      implicated in human neurodegenerative diseases. We have exploited viable null
      alleles of the enzymes of O-GlcNAc cycling to examine the role of O-GlcNAcylation
      in well-characterized Caenorhabditis elegans models of neurodegenerative
      proteotoxicity. O-GlcNAc cycling dramatically modulated the severity of the
      phenotype in transgenic models of tauopathy, amyloid beta-peptide, and
      polyglutamine expansion. Intriguingly, loss of function of O-GlcNAc transferase
      alleviated, whereas loss of O-GlcNAcase enhanced, the phenotype of multiple
      neurodegenerative disease models. The O-GlcNAc cycling mutants act in part by
      altering DAF-16-dependent transcription and modulating the protein degradation
      machinery. These findings suggest that O-GlcNAc levels may directly influence
      neurodegenerative disease progression, thus making the enzymes of O-GlcNAc
      cycling attractive targets for neurodegenerative disease therapies.

PMID- 22988096
TI  - alpha-Synuclein disrupts stress signaling by inhibiting polo-like kinase
      Cdc5/Plk2.
AB  - Parkinson disease (PD) results from the slow, progressive loss of dopaminergic
      neurons in the substantia nigra. Alterations in alpha-synuclein (aSyn), such as
      mutations or multiplications of the gene, are thought to trigger this
      degeneration. Here, we show that aSyn disrupts mitogen-activated protein kinase
      (MAPK)-controlled stress signaling in yeast and human cells, which results in
      inefficient cell protective responses and cell death. aSyn is a substrate of the
      yeast (and human) polo-like kinase Cdc5 (Plk2), and elevated levels of aSyn
      prevent Cdc5 from maintaining a normal level of GTP-bound Rho1, which is an
      essential GTPase that regulates stress signaling. The nine N-terminal amino acids
      of aSyn are essential for the interaction with polo-like kinases. The results
      support a unique mechanism of PD pathology.

PMID- 22988097
TI  - Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells
      requires stronger T-cell receptor signals than conventional CD4 T cells.
AB  - MHC class II-expressing thymocytes and thymic epithelial cells can mediate CD4 T
      cell selection resulting in functionally distinct thymocyte-selected CD4 (T-CD4)
      and epithelial-selected CD4 (E-CD4) T cells, respectively. However, little is
      known about how T-cell receptor (TCR) signaling influences the development of
      these two CD4 T-cell subsets. To study TCR signaling for T-CD4 T-cell
      development, we used a GFP reporter system of Nur77 in which GFP intensity
      directly correlates with TCR signaling strength. T-CD4 T cells expressed higher
      levels of GFP than E-CD4 T cells, suggesting that T-CD4 T cells received stronger
      TCR signaling than E-CD4 T cells during selection. Elimination of Ras GTPase
      activating protein enhanced E-CD4 but decreased T-CD4 T-cell selection
      efficiency, suggesting a shift to negative selection. Conversely, the absence of
      IL-2-inducible T-cell kinase that causes poor E-CD4 T-cell selection due to
      insufficient TCR signaling improved T-CD4 T-cell generation, consistent with
      rescue from negative selection. Strong TCR signaling during T-CD4 T-cell
      development correlates with the expression of the transcription factor
      promyelocytic leukemia zinc finger protein. However, although modulation of the
      signaling strength affected the efficiency of T-CD4 T-cell development during
      positive and negative selection, the signaling strength is not as important for
      the effector function of T-CD4 T cells. These findings indicate that innate T-CD4
      T cells, together with invariant natural killer T cells and gammadelta T cells,
      receive strong TCR signals during their development and that signaling
      requirements for the development and the effector functions are distinct.

PMID- 22988098
TI  - Completion of the core beta-oxidative pathway of benzoic acid biosynthesis in
      plants.
AB  - Despite the importance of benzoic acid (BA) as a precursor for a wide array of
      primary and secondary metabolites, its biosynthesis in plants has not been fully
      elucidated. BA formation from phenylalanine requires shortening of the C(3) side
      chain by two carbon units, which can occur by a non-beta-oxidative route and/or a
      beta-oxidative pathway analogous to the catabolism of fatty acids. Enzymes
      responsible for the first and last reactions of the core BA beta-oxidative
      pathway (cinnamic acid -> cinnamoyl-CoA -> 3-hydroxy-3-phenylpropanoyl-CoA -> 3
      oxo-3-phenylpropanoyl-CoA -> BA-CoA) have previously been characterized in
      petunia, a plant with flowers rich in phenylpropanoid/benzenoid volatile
      compounds. Using a functional genomics approach, we have identified a petunia
      gene encoding cinnamoyl-CoA hydratase-dehydrogenase (PhCHD), a bifunctional
      peroxisomal enzyme responsible for two consecutively occurring unexplored
      intermediate steps in the core BA beta-oxidative pathway. PhCHD spatially,
      developmentally, and temporally coexpresses with known genes in the BA beta
      oxidative pathway, and correlates with emission of benzenoid volatiles. Kinetic
      analysis of recombinant PhCHD revealed it most efficiently converts cinnamoyl-CoA
      to 3-oxo-3-phenylpropanoyl-CoA, thus forming the substrate for the final step in
      the pathway. Down-regulation of PhCHD expression in petunia flowers resulted in
      reduced CHD enzyme activity, as well as decreased formation of BA-CoA, BA and
      their derived volatiles. Moreover, transgenic lines accumulated the PhCHD
      substrate cinnamoyl-CoA and the upstream pathway intermediate cinnamic acid.
      Discovery of PhCHD completes the elucidation of the core BA beta-oxidative route
      in plants, and together with the previously characterized CoA-ligase and thiolase
      enzymes, provides evidence that the whole pathway occurs in peroxisomes.

PMID- 22988099
TI  - Late Pleistocene climate change and the global expansion of anatomically modern
      humans.
AB  - The extent to which past climate change has dictated the pattern and timing of
      the out-of-Africa expansion by anatomically modern humans is currently unclear
      [Stewart JR, Stringer CB (2012) Science 335:1317-1321]. In particular, the
      incompleteness of the fossil record makes it difficult to quantify the effect of
      climate. Here, we take a different approach to this problem; rather than relying
      on the appearance of fossils or archaeological evidence to determine arrival
      times in different parts of the world, we use patterns of genetic variation in
      modern human populations to determine the plausibility of past demographic
      parameters. We develop a spatially explicit model of the expansion of
      anatomically modern humans and use climate reconstructions over the past 120 ky
      based on the Hadley Centre global climate model HadCM3 to quantify the possible
      effects of climate on human demography. The combinations of demographic
      parameters compatible with the current genetic makeup of worldwide populations
      indicate a clear effect of climate on past population densities. Our estimates of
      this effect, based on population genetics, capture the observed relationship
      between current climate and population density in modern hunter-gatherers
      worldwide, providing supporting evidence for the realism of our approach.
      Furthermore, although we did not use any archaeological and anthropological data
      to inform the model, the arrival times in different continents predicted by our
      model are also broadly consistent with the fossil and archaeological records. Our
      framework provides the most accurate spatiotemporal reconstruction of human
      demographic history available at present and will allow for a greater integration
      of genetic and archaeological evidence.

PMID- 22988100
TI  - Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19
      by targeting a membrane coreceptor beta-Klotho.
AB  - MicroRNA-34a (miR-34a) is the most highly elevated hepatic miR in obese mice and
      is also substantially elevated in patients who have steatosis, but its role in
      obesity and metabolic dysfunction remains unclear. After a meal, FGF19 is
      secreted from the ileum; binds to a hepatic membrane receptor complex, FGF19
      receptor 4 and coreceptor beta-Klotho (betaKL); and mediates postprandial
      responses under physiological conditions, but hepatic responses to FGF19
      signaling were shown to be impaired in patients with steatosis. Here, we show an
      unexpected functional link between aberrantly elevated miR-34a and impaired
      betaKL/FGF19 signaling in obesity. In vitro studies show that miR-34a down
      regulates betaKL by binding to the 3' UTR of betaKL mRNA. Adenoviral-mediated
      overexpression of miR-34a in mice decreased hepatic betaKL levels, impaired FGF19
      activated ERK and glycogen synthase kinase signaling, and altered expression of
      FGF19 metabolic target genes. Consistent with these results, betaKL levels were
      decreased and hepatic responses to FGF19 were severely impaired in dietary obese
      mice that have elevated miR-34a. Remarkably, in vivo antisense inhibition of miR
      34a in obese mice partially restored betaKL levels and improved FGF19 target gene
      expression and metabolic outcomes, including decreased liver fat. Further, anti
      miR-34a treatment in primary hepatocytes of obese mice restored FGF19-activated
      ERK and glycogen synthase kinase signaling in a betaKL-dependent manner. These
      results indicate that aberrantly elevated miR-34a in obesity attenuates hepatic
      FGF19 signaling by directly targeting betaKL. The miR-34a/betaKL/FGF19 axis may
      present unique therapeutic targets for FGF19-related human diseases, including
      metabolic disorders and cancer.

PMID- 22988101
TI  - Distinct regions of the Pseudomonas syringae coiled-coil effector AvrRps4 are
      required for activation of immunity.
AB  - Gram-negative phytopathogenic bacteria translocate effector proteins into plant
      cells to subvert host defenses. These effectors can be recognized by plant
      nucleotide-binding-leucine-rich repeat immune receptors, triggering defense
      responses that restrict pathogen growth. AvrRps4, an effector protein from
      Pseudomonas syringae pv. pisi, triggers RPS4-dependent immunity in resistant
      accessions of Arabidopsis. To better understand the molecular basis of AvrRps4
      triggered immunity, we determined the crystal structure of processed AvrRps4
      (AvrRps4(C), residues 134-221), revealing that it forms an antiparallel alpha
      helical coiled coil. Structure-informed mutagenesis reveals an electronegative
      surface patch in AvrRps4(C) required for recognition by RPS4; mutations in this
      region can also uncouple triggering of the hypersensitive response from disease
      resistance. This uncoupling may result from a lower level of defense activation,
      sufficient for avirulence but not for triggering a hypersensitive response.
      Natural variation in AvrRps4 reveals distinct recognition specificities that
      involve a surface-exposed residue. Recently, a direct interaction between AvrRps4
      and Enhanced Disease Susceptibility 1 has been implicated in activation of
      immunity. However, we were unable to detect direct interaction between AvrRps4
      and Enhanced Disease Susceptibility 1 after coexpression in Nicotiana benthamiana
      or in yeast cells. How intracellular plant immune receptors activate defense upon
      effector perception remains an unsolved problem. The structure of AvrRps4(C), and
      identification of functionally important residues for its activation of plant
      immunity, advances our understanding of these processes in a well-defined model
      pathosystem.

PMID- 22988102
TI  - Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and
      phosphatidylglycerol as substrates.
AB  - Depending on growth phase and culture conditions, cardiolipin (CL) makes up 5-15%
      of the phospholipids in Escherichia coli with the remainder being primarily
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). In E. coli, the cls
      and ybhO genes (renamed clsA and clsB, respectively) each encode a CL synthase
      (Cls) that catalyzes the condensation of two PG molecules to form CL and
      glycerol. However, a DeltaclsAB mutant still makes CL in the stationary phase,
      indicating the existence of additional Cls. We identified a third Cls encoded by
      ymdC (renamed clsC). ClsC has sequence homology with ClsA and ClsB, which all
      belong to the phospholipase D superfamily. The DeltaclsABC mutant lacks
      detectible CL regardless of growth phase or growth conditions. CL can be restored
      to near wild-type levels in stationary phase in the triple mutant by expressing
      either clsA or clsB. Expression of clsC alone resulted in a low level of CL in
      the stationary phase, which increased to near wild-type levels by coexpression of
      its neighboring gene, ymdB. CL synthesis by all Cls is increased with increasing
      medium osmolarity during logarithmic growth and in stationary phase. However,
      only ClsA contributes detectible levels of CL at low osmolarity during
      logarithmic growth. Mutation of the putative catalytic motif of ClsC prevents CL
      formation. Unlike eukaryotic Cls (that use PG and CDP-diacylglycerol as
      substrates) or ClsA, the combined YmdB-ClsC used PE as the phosphatidyl donor to
      PG to form CL, which demonstrates a third and unique mode for CL synthesis.

PMID- 22988103
TI  - Molecular conformations, interactions, and properties associated with drug
      efficiency and clinical performance among VEGFR TK inhibitors.
AB  - Analyses of compounds in clinical development have shown that ligand efficient
      molecules with privileged physical properties and low dose are less likely to
      fail in the various stages of clinical testing, have fewer postapproval
      withdrawals, and are less likely to receive black box safety warnings. However,
      detailed side-by-side examination of molecular interactions and properties within
      single drug classes are lacking. As a class, VEGF receptor tyrosine kinase
      inhibitors (VEGFR TKIs) have changed the landscape of how cancer is treated,
      particularly in clear cell renal cell carcinoma, which is molecularly linked to
      the VEGF signaling axis. Despite the clear role of the molecular target, member
      molecules of this validated drug class exhibit distinct clinical efficacy and
      safety profiles in comparable renal cell carcinoma clinical studies. The first
      head-to-head randomized phase III comparative study between active VEGFR TKIs has
      confirmed significant differences in clinical performance [Rini BI, et al. (2011)
      Lancet 378:193-1939]. To elucidate how fundamental drug potency-efficiency is
      achieved and impacts differentiation within the VEGFR TKI class, we determined
      potencies, time dependence, selectivities, and X-ray structures of the drug
      kinase complexes using a VEGFR2 TK construct inclusive of the important
      juxtamembrane domain. Collectively, the studies elucidate unique drug-kinase
      interactions that are dependent on distinct juxtamembrane domain conformations,
      resulting in significant potency and ligand efficiency differences. The
      identified structural trends are consistent with in vitro measurements, which
      translate well to clinical performance, underscoring a principle that may be
      broadly applicable to prospective drug design for optimal in vivo performance.

PMID- 22988104
TI  - Dual signaling by innate and adaptive immune receptors is required for TLR7
      induced B-cell-mediated autoimmunity.
AB  - Toll-like receptor 7 (Tlr7) has been linked to systemic lupus disease incidence
      in humans and mice, but how TLR7 potentiates autoimmunity is unclear. We used a
      Tlr7 transgenic (tg) mouse model to investigate the cellular and molecular events
      required to induce spontaneous autoimmunity through increased TLR7 activity. We
      determined that Tlr7 exerts B-cell-intrinsic effects in promoting spontaneous
      germinal center (GC) and plasmablast B-cell development, and that these B-cell
      subsets are dependent on T-cell-derived signals through CD40L and SLAM-associated
      protein (SAP), but not IL-17. Antigen specificity also factored into TLR7-induced
      disease, as both a restricted T cell receptor (TCR) specificity and MHC haplotype
      H2(k/k) protected Tlr7tg mice from spontaneous lymphocyte activation and
      autoantibody production. Inflammatory myeloid cell expansion and autoimmunity did
      not develop in Tlr7tgIgH(-/-) mice, suggesting either that spontaneous TLR7
      activation does not occur in dendritic cells, or, if it does occur, cannot drive
      these events in the absence of B-cell aid. These data indicate that autoimmune
      disease in Tlr7tg mice is contingent upon B cells receiving stimulation both
      through innate pathways and T-cell-derived signals and suggest a codependent
      relationship between B cells and T cells in the development of autoimmunity.

PMID- 22988106
TI  - Upper thermal limits of Drosophila are linked to species distributions and
      strongly constrained phylogenetically.
AB  - Upper thermal limits vary less than lower limits among related species of
      terrestrial ectotherms. This pattern may reflect weak or uniform selection on
      upper limits, or alternatively tight evolutionary constraints. We investigated
      this issue in 94 Drosophila species from diverse climates and reared in a common
      environment to control for plastic effects that may confound species comparisons.
      We found substantial variation in upper thermal limits among species, negatively
      correlated with annual precipitation at the central point of their distribution
      and also with the interaction between precipitation and maximum temperature,
      showing that heat resistance is an important determinant of Drosophila species
      distributions. Species from hot and relatively dry regions had higher resistance,
      whereas resistance was uncorrelated with temperature in wetter regions. Using a
      suite of analyses we showed that phylogenetic signal in heat resistance reflects
      phylogenetic inertia rather than common selection pressures. Current species
      distributions are therefore more likely to reflect environmental sorting of
      lineages rather than local adaptation. Similar to previous studies, thermal
      safety margins were small at low latitudes, with safety margins smallest for
      species occupying both humid and dry tropical environments. Thus, species from a
      range of environments are likely to be at risk owing to climate change. Together
      these findings suggest that this group of insects is unlikely to buffer global
      change effects through marked evolutionary changes, highlighting the importance
      of facilitating range shifts for maintaining biodiversity.

PMID- 22988105
TI  - Structural basis for the sheddase function of human meprin beta metalloproteinase
      at the plasma membrane.
AB  - Ectodomain shedding at the cell surface is a major mechanism to regulate the
      extracellular and circulatory concentration or the activities of signaling
      proteins at the plasma membrane. Human meprin beta is a 145-kDa disulfide-linked
      homodimeric multidomain type-I membrane metallopeptidase that sheds membrane
      bound cytokines and growth factors, thereby contributing to inflammatory
      diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid
      precursor protein (APP) at the beta-secretase site, giving rise to amyloidogenic
      peptides. We have solved the X-ray crystal structure of a major fragment of the
      meprin beta ectoprotein, the first of a multidomain oligomeric transmembrane
      sheddase, and of its zymogen. The meprin beta dimer displays a compact shape,
      whose catalytic domain undergoes major rearrangement upon activation, and reveals
      an exosite and a sugar-rich channel, both of which possibly engage in substrate
      binding. A plausible structure-derived working mechanism suggests that substrates
      such as APP are shed close to the plasma membrane surface following an "N-like"
      chain trace.

PMID- 22988107
TI  - Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway
      smooth muscle contraction.
AB  - Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are
      hallmark features of inflammatory airway diseases, including asthma. Here, we
      show that the recently identified calcium-activated chloride channel (CaCC)
      TMEM16A is expressed in the adult airway surface epithelium and ASM. The
      epithelial expression is increased in asthmatics, particularly in secretory
      cells. Based on this and the proposed functions of CaCC, we hypothesized that
      TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and
      ASM contraction. We used a high-throughput screen to identify small-molecule
      blockers of TMEM16A-CaCC channels. We show that inhibition of TMEM16A-CaCC
      significantly impairs mucus secretion in primary human airway surface epithelial
      cells. Furthermore, inhibition of TMEM16A-CaCC significantly reduces mouse and
      human ASM contraction in response to cholinergic agonists. TMEM16A-CaCC blockers,
      including those identified here, may positively impact multiple causes of asthma
      symptoms.

PMID- 22988108
TI  - Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T
      cell abundance and function during inflammatory hypoxia of the mucosa.
AB  - Recent studies have demonstrated dramatic shifts in metabolic supply-and-demand
      ratios during inflammation, a process resulting in localized tissue hypoxia
      within inflammatory lesions ("inflammatory hypoxia"). As part of the adaptive
      immune response, T cells are recruited to sites of inflammatory hypoxia. Given
      the profound effects of hypoxia on gene regulation, we hypothesized that T-cell
      differentiation is controlled by hypoxia. To pursue this hypothesis, we analyzed
      the transcriptional consequences of ambient hypoxia (1% oxygen) on a broad panel
      of T-cell differentiation factors. Surprisingly, these studies revealed
      selective, robust induction of FoxP3, a key transcriptional regulator for
      regulatory T cells (Tregs). Studies of promoter binding or loss- and gain-of
      function implicated hypoxia-inducible factor (HIF)-1alpha in inducing FoxP3.
      Similarly, hypoxia enhanced Treg abundance in vitro and in vivo. Finally, Treg
      intrinsic HIF-1alpha was required for optimal Treg function and Hif1a-deficient
      Tregs failed to control T-cell-mediated colitis. These studies demonstrate that
      hypoxia is an intrinsic molecular cue that promotes FoxP3 expression, in turn
      eliciting potent anti-inflammatory mechanisms to limit tissue damage in
      conditions of reduced oxygen availability.

PMID- 22988109
TI  - Closely related bird species demonstrate flexibility between beak morphology and
      underlying developmental programs.
AB  - The astonishing variation in the shape and size of bird beaks reflects a wide
      range of dietary specializations that played an important role in avian
      diversification. Among Darwin's finches, ground finches (Geospiza spp.) have
      beaks that represent scaling variations of the same shape, which are generated by
      alterations in the signaling pathways that regulate growth of the two skeletal
      components of the beak: the prenasal cartilage (pnc) and the premaxillary bone
      (pmx). Whether this developmental mechanism is responsible for variation within
      groups of other closely related bird species, however, has remained unknown.
      Here, we report that the Caribbean bullfinches (Loxigilla spp.), which are
      closely related to Darwin's finches, have independently evolved beaks of a novel
      shape, different from Geospiza, but also varying from each other only in scaling.
      However, despite sharing the same beak shape, the signaling pathways and tissues
      patterning Loxigilla beaks differ among the three species. In Loxigilla noctis,
      as in Geospiza, the pnc develops first, shaped by Bmp4 and CaM signaling,
      followed by the development of the pmx, regulated by TGFbetaIIr, beta-catenin,
      and Dkk3 signaling. In contrast, beak morphogenesis in Loxigilla violacea and
      Loxigilla portoricensis is generated almost exclusively by the pmx through a
      mechanism in which Ihh and Bmp4 synergize to promote expansion of bone tissue.
      Together, our results demonstrate high flexibility in the relationship between
      morphology and underlying developmental causes, where different developmental
      programs can generate identical shapes, and similar developmental programs can
      pattern different shapes.

PMID- 22988111
TI  - C-terminal region of the UV-B photoreceptor UVR8 initiates signaling through
      interaction with the COP1 protein.
AB  - UV-B light initiates photomorphogenic responses in plants. Arabidopsis UV
      RESISTANCE LOCUS8 (UVR8) specifically mediates these responses by functioning as
      a UV-B photoreceptor. UV-B exposure converts UVR8 from a dimer to a monomer,
      stimulates the rapid accumulation of UVR8 in the nucleus, where it binds to
      chromatin, and induces interaction of UVR8 with CONSTITUTIVELY PHOTOMORPHOGENIC1
      (COP1), which functions with UVR8 to control photomorphogenic UV-B responses.
      Although the crystal structure of UVR8 reveals the basis of photoreception, it
      does not show how UVR8 initiates signaling through interaction with COP1. Here we
      report that a region of 27 amino acids from the C terminus of UVR8 (C27) mediates
      the interaction with COP1. The C27 region is necessary for UVR8 function in the
      regulation of gene expression and hypocotyl growth suppression in Arabidopsis.
      However, UVR8 lacking C27 still undergoes UV-B-induced monomerization in both
      yeast and plant protein extracts, accumulates in the nucleus in response to UV-B,
      and interacts with chromatin at the UVR8-regulated ELONGATED HYPOCOTYL5 (HY5)
      gene. The UV-B-dependent interaction of UVR8 and COP1 is reproduced in yeast
      cells and we show that C27 is both necessary and sufficient for the interaction
      of UVR8 with the WD40 domain of COP1. Furthermore, we show that C27 interacts in
      yeast with the REPRESSOR OF UV-B PHOTOMORPHOGENESIS proteins, RUP1 and RUP2,
      which are negative regulators of UVR8 function. Hence the C27 region has a key
      role in UVR8 function.

PMID- 22988112
TI  - New Caledonian crows reason about hidden causal agents.
AB  - The ability to make inferences about hidden causal mechanisms underpins
      scientific and religious thought. It also facilitates the understanding of social
      interactions and the production of sophisticated tool-using behaviors. However,
      although animals can reason about the outcomes of accidental interventions, only
      humans have been shown to make inferences about hidden causal mechanisms. Here,
      we show that tool-making New Caledonian crows react differently to an observable
      event when it is caused by a hidden causal agent. Eight crows watched two series
      of events in which a stick moved. In the first set of events, the crows observed
      a human enter a hide, a stick move, and the human then leave the hide. In the
      second, the stick moved without a human entering or exiting the hide. The crows
      inspected the hide and abandoned probing with a tool for food more often after
      the second, unexplained series of events. This difference shows that the crows
      can reason about a hidden causal agent. Comparative studies with the methodology
      outlined here could aid in elucidating the selective pressures that led to the
      evolution of this cognitive ability.

PMID- 22988110
TI  - Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple
      myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).
AB  - Hypothesis directed proteomics offers higher throughput over global analyses. We
      show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929
      multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected
      BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec).
      BCR-ABL is the driving mutation in chronic myeloid leukemia (CML) and is uncommon
      to other cancers. Three different IP-MS experiments central to cell signaling
      pathways were sufficient to discover a BCR-ABL fusion in H929 cells:
      phosphotyrosine (pY) peptide IP, p85 regulatory subunit of phosphoinositide-3
      kinase (PI3K) IP, and the GRB2 adaptor IP. The pY peptides inform tyrosine kinase
      activity, p85 IP informs the activating adaptors and receptor tyrosine kinases
      (RTKs) involved in AKT activation and GRB2 IP identifies RTKs and adaptors
      leading to ERK activation. Integration of the bait-prey data from the three
      separate experiments identified the BCR-ABL protein complex, which was confirmed
      by biochemistry, cytogenetic methods, and DNA sequencing revealed the e14a2
      fusion transcript. The tyrosine phosphatase SHP2 and the GAB2 adaptor protein,
      important for MAPK signaling, were common to all three IP-MS experiments. The
      comparative treatment of tyrosine kinase inhibitor (TKI) drugs revealed only
      imatinib, the standard of care in CML, was inhibitory to BCR-ABL leading to down
      regulation of pERK and pS6K and inhibiting cell proliferation. These data suggest
      a model for directed proteomics from patient tumor samples for selecting the
      appropriate TKI drug(s) based on IP and LC-MS/MS. The data also suggest that MM
      patients, in addition to CML patients, may benefit from BCR-ABL diagnostic
      screening.

PMID- 22988113
TI  - Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon.
AB  - Quorum sensing allows bacteria to sense and respond to changes in population
      density. Acyl-homoserine lactones serve as quorum-sensing signals for many
      Proteobacteria, and acyl-homoserine lactone signaling is known to control
      cooperative activities. Quorum-controlled activities vary from one species to
      another. Quorum-sensing controls a constellation of genes in the opportunistic
      pathogen Pseudomonas aeruginosa, which thrives in a number of habitats ranging
      from soil and water to animal hosts. We hypothesized that there would be
      significant variation in quorum-sensing regulons among strains of P. aeruginosa
      isolated from different habitats and that differences in the quorum-sensing
      regulons might reveal insights about the ecology of P. aeruginosa. As a test of
      our hypothesis we used RNA-seq to identify quorum-controlled genes in seven P.
      aeruginosa isolates of diverse origins. Although our approach certainly overlooks
      some quorum-sensing-regulated genes we found a shared set of genes, i.e., a core
      quorum-controlled gene set, and we identified distinct, strain-variable sets of
      quorum-controlled genes, i.e., accessory genes. Some quorum-controlled genes in
      some strains were not present in the genomes of other strains. We detected a
      correlation between traits encoded by some genes in the strain-variable subsets
      of the quorum regulons and the ecology of the isolates. These findings indicate a
      role for quorum sensing in extension of the range of habitats in which a species
      can thrive. This study also provides a framework for understanding the molecular
      mechanisms by which quorum-sensing systems operate, the evolutionary pressures by
      which they are maintained, and their importance in disparate ecological contexts.

PMID- 22988114
TI  - DEC-205 is a cell surface receptor for CpG oligonucleotides.
AB  - Synthetic CpG oligonucleotides (ODN) have potent immunostimulatory properties
      exploited in clinical vaccine trials. How CpG ODN are captured and delivered to
      the intracellular receptor TLR9, however, has been elusive. Here we show that DEC
      205, a multilectin receptor expressed by a variety of cells, is a receptor for
      CpG ODN. When CpG ODN are used as an adjuvant, mice deficient in DEC-205 have
      impaired dendritic cell (DC) and B-cell maturation, are unable to make some
      cytokines such as IL-12, and display suboptimal cytotoxic T-cell responses. We
      reveal that DEC-205 directly binds class B CpG ODN and enhances their uptake. The
      CpG-ODN binding function of DEC-205 is conserved between mouse and man, although
      human DEC-205 preferentially binds a specific class B CpG ODN that has been
      selected for human clinical trials. Our findings identify an important receptor
      for class B CpG ODN and reveal a unique function for DEC-205.

PMID- 22988115
TI  - Identification of a BAHD acetyltransferase that produces protective acyl sugars
      in tomato trichomes.
AB  - Glandular secreting trichomes on the surface of tomato plants and many of its
      relatives in the Solanaceae produce a mixture of O-acyl sugars that contribute to
      insect resistance. The majority of acyl sucroses produced by the cultivated
      tomato (Solanum lycopersicum) contain three or four short chain aliphatic acyl
      esters, and tetra-acyl sucroses have an acetyl group as one of the acyl chains.
      We previously reported overlapping S. lycopersicum * Solanum pennellii
      introgression lines (ILs) that fail to accumulate high levels of acetylated tetra
      acyl sucroses. A survey of the annotated genes in this region of cultivated
      tomato chromosome 1 revealed three candidate acyltransferases that were tested
      for function using virus-induced gene silencing. A member of the BAHD family of
      acyltransferases (Solyc01g105580, SlAT2) was shown to encode an acetyl-CoA
      dependent acyltransferase enzyme capable of acyl sucrose acetylation in vitro.
      RNAi suppression of SlAT2 in transgenic S. lycopersicum cv. M82 resulted in
      reduced acyl sugar acetylation, whereas expression of the functional S.
      lycopersicum allele of SlAT2 in the triacyl sucrose producing IL1-3 restored the
      ability of the IL to synthesize acetylated tetra-acyl sugars. Transgenic plants
      with the SlAT2 promoter driving GFP expression showed fluorescence in tips cells
      of long, slender trichomes that is consistent with acyl sugar acetylation
      occurring in these cells.

PMID- 22988116
TI  - Distinct roles of metabotropic glutamate receptor dimerization in agonist
      activation and G-protein coupling.
AB  - The eight metabotropic glutamate receptors (mGluRs) are key modulators of
      synaptic transmission and are considered promising targets for the treatment of
      various brain disorders. Whereas glutamate acts at a large extracellular domain,
      allosteric modulators have been identified that bind to the seven transmembrane
      domain (7TM) of these dimeric G-protein-coupled receptors (GPCRs). We show here
      that the dimeric organization of mGluRs is required for the modulation of active
      and inactive states of the 7TM by agonists, but is not necessary for G-protein
      activation. Monomeric mGlu2, either as an isolated 7TM or in full-length,
      purified and reconstituted into nanodiscs, couples to G proteins upon direct
      activation by a positive allosteric modulator. However, only a reconstituted full
      length dimeric mGlu2 activates G protein upon glutamate binding, suggesting that
      dimerization is required for glutamate induced activation. These data show that,
      even for such well characterized GPCR dimers like mGluR2, a single 7TM is
      sufficient for G-protein coupling. Despite this observation, the necessity of
      dimeric architecture for signaling induced by the endogenous ligand glutamate
      confirms that the central core of signaling complex is dimeric.

PMID- 22988117
TI  - Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and
      inhibits somatic cell reprogramming.
AB  - The homeodomain transcription factor Nanog plays an important role in embryonic
      stem cell (ESC) self-renewal and is essential for acquiring ground-state
      pluripotency during reprogramming. Understanding how Nanog is transcriptionally
      regulated is important for further dissecting mechanisms of ESC pluripotency and
      somatic cell reprogramming. Here, we report that Nanog is subjected to a negative
      autoregulatory mechanism, i.e., autorepression, in ESCs, and that such
      autorepression requires the coordinated action of the Nanog partner and
      transcriptional repressor Zfp281. Mechanistically, Zfp281 recruits the NuRD
      repressor complex onto the Nanog locus and maintains its integrity to mediate
      Nanog autorepression and, functionally, Zfp281-mediated Nanog autorepression
      presents a roadblock to efficient somatic cell reprogramming. Our results
      identify a unique transcriptional regulatory mode of Nanog gene expression and
      shed light into the mechanistic understanding of Nanog function in pluripotency
      and reprogramming.

PMID- 22988118
TI  - CD73-generated adenosine facilitates Toxoplasma gondii differentiation to long
      lived tissue cysts in the central nervous system.
AB  - Toxoplasma gondii is an obligate intracellular protozoan pathogen that traffics
      to the central nervous system (CNS) following invasion of its host. In the CNS,
      T. gondii undergoes transformation from a rapidly dividing tachyzoite to a long
      lived, slow-dividing bradyzoite contained within cysts. The role of extracellular
      adenosine in T. gondii pathogenesis has not been previously investigated. T.
      gondii uses host purines such as adenosine for its energy needs, as it is unable
      to make its own. Here, we show that CD73(-/-) mice, which lack the ability to
      generate extracellular adenosine, are protected from T. gondii chronic infection,
      with significantly fewer cysts and reduced susceptibility to reactivation of
      infection in the CNS independent of host effector function. Parasite
      dissemination to the brain was unimpaired in CD73(-/-) hosts, suggesting that the
      reduced cyst number is due to impaired parasite differentiation in the CNS.
      Confirming this, T. gondii tachyzoites formed fewer cysts following alkaline pH
      stress in astrocytes isolated from CD73(-/-) mice compared with wild type, and in
      fibroblasts treated with a CD73 inhibitor. Cyst formation was rescued in CD73(-/
      ) astrocytes supplemented with adenosine, but not with adenosine receptor agonist
      5'-N-ethylcarboxamidoadenosine. Furthermore, mice lacking adenosine receptors had
      no defect in cyst formation. Based on these findings, we conclude that CD73
      expression promotes Toxoplasma bradyzoite differentiation and cyst formation by a
      mechanism dependent on the generation of adenosine, but independent of adenosine
      receptor signaling. Overall, these findings suggest that modulators of
      extracellular adenosine may be used to develop therapies aimed at defending
      against human toxoplasmosis.

PMID- 22988119
TI  - Diet-induced metabolic change induces estrogen-independent allometric mammary
      growth.
AB  - Lifetime breast cancer risk reflects an unresolved combination of early life
      factors including diet, body mass index, metabolic syndrome, obesity, and age at
      first menses. In parallel, the onset of allometric growth by the mammary glands
      around puberty is widely held to be estrogen (E)-dependent. Here we report that
      several physiological changes associated with metabolic syndrome in response to a
      diet supplemented with the trans-10, cis-12 isomer of conjugated linoleic acid
      lead to ovary-independent allometric growth of the mammary ducts. The E
      independence of this diet-induced growth was highlighted by the fact that it
      occurred both in male mice and with pharmacological inhibition of either E
      receptor function or E biosynthesis. Reversal of the metabolic phenotype with the
      peroxisome proliferator-activated receptor-gamma agonist rosiglitazone abrogated
      diet-induced mammary growth. A role for hyperinsulinemia and increased insulin
      like growth factor-I receptor (IGF-IR) expression during mammary growth induced
      by the trans-10, cis-12 isomer of conjugated linoleic acid was confirmed by its
      reversal upon pharmacological inhibition of IGF-IR function. Diet-stimulated
      ductal growth also increased mammary tumorigenesis in ovariectomized polyomavirus
      middle T-antigen mice. Our data demonstrate that diet-induced metabolic
      dysregulation, independently of ovarian function, stimulates allometric growth
      within the mammary glands via an IGF-IR-dependent mechanism.

PMID- 22988120
TI  - siRNA silencing of estrogen receptor-alpha expression specifically in medial
      preoptic area neurons abolishes maternal care in female mice.
AB  - The medial preoptic area has been shown to be intricately involved in many
      behaviors, including locomotion, sexual behavior, maternal care, and aggression.
      The gene encoding estrogen receptor-alpha (ERalpha) protein is expressed in
      preoptic area neurons, and a very dense immunoreactive field of ERalpha is found
      in the preoptic region. ERalpha knockout animals show deficits in maternal care
      and sexual behavior and fail to exhibit increases in these behaviors in response
      to systemic estradiol treatment. In the present study, we used viral-vector
      mediated RNA interference to silence ERalpha expression specifically in the
      preoptic area of female mice and measured a variety of behaviors, including
      social and sexual aggression, maternal care, and arousal activity. Suppression of
      ERalpha in the preoptic area almost completely abolished maternal care,
      significantly increasing the latency to pup retrieval and significantly reducing
      the time the moms spent nursing and licking the pups. Strikingly, maternal
      aggression toward a male intruder was not different between control and preoptic
      ERalpha-silenced mice, demonstrating the remarkably specific role of ERalpha in
      these neurons. Reduction of ERalpha expression in preoptic neurons significantly
      decreased sexual behavior in female mice and increased aggression toward both
      sexual partners and male intruders in a seminatural environment. Estrogen
      dependent increases in arousal, measured by home cage activity, were not mediated
      by ERalpha expression in the preoptic neurons we targeted, as ERalpha-suppressed
      mice had increases similar to control mice. Thus, we have established that a
      specific gene in a specific group of neurons is required for a crucially
      important natural behavior.

PMID- 22988121
TI  - Transient receptor potential channel TRPC5 is essential for P-glycoprotein
      induction in drug-resistant cancer cells.
AB  - An attractive strategy to overcome multidrug resistance in cancer chemotherapy is
      to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells
      to remove cytotoxic drugs from cells. In the present study, a Ca(2+)-permeable
      channel TRPC5 was found to be overproduced together with P-gp in adriamycin
      resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5
      activity/expression reduced the P-gp induction and caused a remarkable reversal
      of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of
      adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth
      of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was
      the transcriptional factor that links the TRPC5 activity to P-gp production.
      Together, we demonstrated an essential role of TRPC5-NFATc3-P-gp signaling
      cascade in P-gp induction in drug-resistant cancer cells.

PMID- 22988124
TI  - Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify
      candidate biomarkers.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular
      disorder caused by contractions of repetitive elements within the macrosatellite
      D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result,
      there is currently no effective treatment available for this disease. To better
      understand the pathophysiology of FSHD and develop mRNA-based biomarkers of
      affected muscles, we compared global analysis of gene expression in two distinct
      muscles obtained from a large number of FSHD subjects and their unaffected first
      degree relatives. Gene expression in two muscle types was analyzed using GeneChip
      Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease
      involvement; and deltoid, which is relatively uninvolved. For both muscle types,
      the expression differences were mild: using relaxed cutoffs for differential
      expression (fold change >=1.2; nominal P value <0.01), we identified 191 and 110
      genes differentially expressed between affected and control samples of biceps and
      deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a
      false-discovery rate of <0.25 reduced the number of differentially expressed
      genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered
      in this study were used as a "molecular signature" in a validation study of an
      additional 26 subjects and predicted them as FSHD or control with 90% accuracy
      based on biceps and 80% accuracy based on deltoids.

PMID- 22988125
TI  - Regulation of bacterial photosynthesis genes by the small noncoding RNA PcrZ.
AB  - The small RNA PcrZ (photosynthesis control RNA Z) of the facultative phototrophic
      bacterium Rhodobacter sphaeroides is induced upon a drop of oxygen tension with
      similar kinetics to those of genes for components of photosynthetic complexes.
      High expression of PcrZ depends on PrrA, the response regulator of the PrrB/PrrA
      two-component system with a central role in redox regulation in R. sphaeroides.
      In addition the FnrL protein, an activator of some photosynthesis genes at low
      oxygen tension, is involved in redox-dependent expression of this small (s)RNA.
      Overexpression of full-length PcrZ in R. sphaeroides affects expression of a
      small subset of genes, most of them with a function in photosynthesis. Some mRNAs
      from the photosynthetic gene cluster were predicted to be putative PcrZ targets
      and results from an in vivo reporter system support these predictions. Our data
      reveal a negative effect of PcrZ on expression of its target mRNAs. Thus, PcrZ
      counteracts the redox-dependent induction of photosynthesis genes, which is
      mediated by protein regulators. Because PrrA directly activates photosynthesis
      genes and at the same time PcrZ, which negatively affects photosynthesis gene
      expression, this is one of the rare cases of an incoherent feed-forward loop
      including an sRNA. Our data identified PcrZ as a trans acting sRNA with a direct
      regulatory function in formation of photosynthetic complexes and provide a model
      for the control of photosynthesis gene expression by a regulatory network
      consisting of proteins and a small noncoding RNA.

PMID- 22988126
TI  - Science faculty's subtle gender biases favor male students.
AB  - Despite efforts to recruit and retain more women, a stark gender disparity
      persists within academic science. Abundant research has demonstrated gender bias
      in many demographic groups, but has yet to experimentally investigate whether
      science faculty exhibit a bias against female students that could contribute to
      the gender disparity in academic science. In a randomized double-blind study (n =
      127), science faculty from research-intensive universities rated the application
      materials of a student-who was randomly assigned either a male or female name-for
      a laboratory manager position. Faculty participants rated the male applicant as
      significantly more competent and hireable than the (identical) female applicant.
      These participants also selected a higher starting salary and offered more career
      mentoring to the male applicant. The gender of the faculty participants did not
      affect responses, such that female and male faculty were equally likely to
      exhibit bias against the female student. Mediation analyses indicated that the
      female student was less likely to be hired because she was viewed as less
      competent. We also assessed faculty participants' preexisting subtle bias against
      women using a standard instrument and found that preexisting subtle bias against
      women played a moderating role, such that subtle bias against women was
      associated with less support for the female student, but was unrelated to
      reactions to the male student. These results suggest that interventions
      addressing faculty gender bias might advance the goal of increasing the
      participation of women in science.

PMID- 22988128
TI  - Mucus supramolecular topology: an elusive riddle.

PMID- 22988127
TI  - Features of the Arabidopsis recombination landscape resulting from the combined
      loss of sequence variation and DNA methylation.
AB  - The rate of meiotic crossing over (CO) varies considerably along chromosomes,
      leading to marked distortions between physical and genetic distances. The causes
      underlying this variation are being unraveled, and DNA sequence and chromatin
      states have emerged as key factors. However, the extent to which the suppression
      of COs within the repeat-rich pericentromeric regions of plant and mammalian
      chromosomes results from their high level of DNA polymorphisms and from their
      heterochromatic state, notably their dense DNA methylation, remains unknown.
      Here, we test the combined effect of removing sequence polymorphisms and repeat
      associated DNA methylation on the meiotic recombination landscape of an
      Arabidopsis mapping population. To do so, we use genome-wide DNA methylation data
      from a large panel of isogenic epigenetic recombinant inbred lines (epiRILs) to
      derive a recombination map based on 126 meiotically stable, differentially
      methylated regions covering 81.9% of the genome. We demonstrate that the
      suppression of COs within pericentromeric regions of chromosomes persists in this
      experimental setting. Moreover, suppression is reinforced within 3-Mb regions
      flanking pericentromeric boundaries, and this effect appears to be compensated by
      increased recombination activity in chromosome arms. A direct comparison with 17
      classical Arabidopsis crosses shows that these recombination changes place the
      epiRILs at the boundary of the range of natural variation but are not severe
      enough to transgress that boundary significantly. This level of robustness is
      remarkable, considering that this population represents an extreme with key
      recombination barriers having been forced to a minimum.

PMID- 22988130
TI  - Antibody isolation from immunized animals: comparison of phage display and
      antibody discovery via V gene repertoire mining.
AB  - Phage display has enabled the rapid isolation of antigen-specific antibodies from
      combinatorial libraries of V(H) and V(L) genes obtained from lymphocytes of
      immunized animals. Recently, a different approach to antibody isolation that
      circumvents library screening and instead relies on the mining of the V(H) and
      V(L) gene repertoires obtained by high throughput sequencing of cDNAs from bone
      marrow antibody-secreting cells was reported. Here we compared the antibodies
      obtained via phage library screening or via repertoire mining of V gene cDNAs
      obtained from total splenocytes of mice immunized with the hapten trinitrophenyl
      (TNP) conjugated to carrier proteins. We show that, despite the large
      heterogeneity of B lymphocytes in the spleen, the most abundant V genes encoded
      antigen-specific antibodies, indicating that total splenocytes can be used in
      place of bone marrow plasma cells for antibody discovery at least in high titer
      animals. While both phage display and repertoire mining yielded antigen-specific
      antibodies showing comparable affinities by enzyme-linked immunosorbent assay
      analysis, clones obtained by the latter approach displayed higher selectivity
      towards TNP relative to control haptens. Interestingly, the antibody genes
      isolated by phage display were of low abundance or absent from the V gene
      repertoire obtained by 454 sequencing. Similarly, the highly abundant V genes
      identified by repertoire mining, that as soluble antibodies were antigen
      specific, were found to be poorly displayed on phage and were not enriched by
      phage panning. Thus, our results reveal that phage display and repertoire mining
      of immune repertoires are complementary technologies that can yield different
      antigen-specific antibody clones.

PMID- 22988131
TI  - Engineering antibodies for the 21st century.

PMID- 22988132
TI  - The IgM CH2 domain as covalently linked homodimerization module for the
      generation of fusion proteins with dual specificity.
AB  - Dimeric assembly of antibody fragments and other therapeutic molecules can result
      in increased binding and improved bioactivity. Here, we investigated the use of
      the IgM heavy chain domain 2 (MHD2) as covalently linked homodimerization module.
      Fusion of single-chain fragment variable (scFv) molecules directed against
      epidermal growth factor receptor (EGFR) and human epidermal growth factor
      receptor 2 to the N- and/or C-terminus of the MHD2, respectively, resulted in
      molecules with single or dual specificity for tumor cells. Bispecific tetravalent
      molecules were further generated by fusing a bispecific single-chain diabody
      directed against EGFR and epithelial cell adhesion molecule to the N-terminus of
      the MHD2. By combining an anti-EGFR scFv with a single-chain derivative of tumor
      necrosis factor, a tetravalent bifunctional fusion protein was produced. This
      fusion protein exhibited improved TNF activity, also mimicking the membrane-bound
      form of TNF, as shown by the activation of TNFR2-mediated cell killing.
      Furthermore, the scFv moiety allowed for an antigen-dependent delivery of TNF to
      EGFR-positive cells and an improved stimulatory TNF action on these cells. Thus,
      we established the MHD2 as a versatile module for the generation of bispecific
      and bifunctional fusion proteins.

PMID- 22988133
TI  - A novel hSH3 domain scaffold engineered to bind folded domains in CD2BP2 and HIV
      capsid protein.
AB  - Engineered protein scaffolds destined to target and inhibit molecular
      interactions in the context of disease bear great diagnostic and therapeutic
      potential. Apart from antibodies several alternative scaffolds have been
      exploited over the years making use of the fact that individual domain families
      are best suited for certain target families. Here we capitalize on the helically
      extended SH3 domain hSH3N of the ADAP protein as loop-randomized template that
      was tested against HIV capsid (CA) protein and the GYF domain of human CD2BP2 as
      molecular targets. Phage display of mutant proteins resulted in the isolation of
      variants with changes in all randomized positions compared with wild-type hSH3N.
      The soluble scaffolds bind with 340 and 600 nM affinity to CA and CD2BP2,
      respectively, and employ large molecular surfaces to pull out these targets from
      complex mixtures.

PMID- 22988134
TI  - Compensatory vasodilatation during hypoxic exercise: mechanisms responsible for
      matching oxygen supply to demand.
AB  - Hypoxia can have profound influences on the circulation. In humans, acute
      exposure to moderate hypoxia has been demonstrated to result in vasodilatation in
      the coronary, cerebral, splanchnic and skeletal muscle vascular beds. The
      combination of submaximal exercise and hypoxia produces a 'compensatory'
      vasodilatation and augmented blood flow in contracting skeletal muscles relative
      to the same level of exercise under normoxic conditions. This augmented
      vasodilatation exceeds that predicted by a simple sum of the individual dilator
      responses to hypoxia alone and normoxic exercise. Additionally, this enhanced
      hypoxic exercise hyperaemia is proportional to the hypoxia-induced fall in
      arterial oxygen (O(2)) content, thus preserving muscle O(2) delivery and ensuring
      it is matched to demand. Several vasodilator pathways have been proposed and
      examined as likely regulators of skeletal muscle blood flow in response to
      changes in arterial O(2) content. The purpose of this review is to put into
      context the present evidence regarding mechanisms responsible for the
      compensatory vasodilatation observed during hypoxic exercise in humans. Along
      these lines, this review will highlight the interactions between various local
      metabolic and endothelial derived substances that influence vascular tone during
      hypoxic exercise.

PMID- 22988135
TI  - Voluntary scheduled exercise alters diurnal rhythms of behaviour, physiology and
      gene expression in wild-type and vasoactive intestinal peptide-deficient mice.
AB  - The circadian system co-ordinates the temporal patterning of behaviour and many
      underlying biological processes. In some cases, the regulated outputs of the
      circadian system, such as activity, may be able to feed back to alter core clock
      processes. In our studies, we used four wheel-access conditions (no access; free
      access; early night; and late night) to manipulate the duration and timing of
      activity while under the influence of a light-dark cycle. In wild-type mice,
      scheduled wheel access was able to increase ambulatory activity, inducing a level
      of exercise driven at various phases of the light-dark cycle. Scheduled exercise
      also manipulated the magnitude and phasing of the circadian-regulated outputs of
      heart rate and body temperature. At a molecular level, the phasing and amplitude
      of PER2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN and peripheral
      tissues of Per2::Luc knockin mice were altered by scheduled exercise. We then
      tested whether scheduled wheel access could improve deficits observed in
      vasointestinal polypeptide-deficient mice under the influence of a light-dark
      cycle. We found that scheduled wheel access during the late night improved many
      of the behavioural, physiological and molecular deficits previously described in
      vasointestinal polypeptide-deficient mice. Our results raise the possibility that
      scheduled exercise could be used as a tool to modulate daily rhythms and, when
      applied, may counteract some of the negative impacts of ageing and disease on the
      circadian system.

PMID- 22988136
TI  - beta-Adrenergic stimulation increases the intra-sarcoplasmic reticulum Ca2+
      threshold for Ca2+ wave generation.
AB  - beta-Adrenergic signalling induces positive inotropic effects on the heart that
      associate with pro-arrhythmic spontaneous Ca(2+) waves. A threshold level of
      sarcoplasmic reticulum (SR) Ca(2+) ([Ca(2+)](SR)) is necessary to trigger Ca(2+)
      waves, and whether the increased incidence of Ca(2+) waves during beta-adrenergic
      stimulation is due to an alteration in this threshold remains controversial.
      Using the low-affinity Ca(2+) indicator fluo-5N entrapped within the SR of rabbit
      ventricular myocytes, we addressed this controversy by directly monitoring
      [Ca(2+)](SR) and Ca(2+) waves during beta-adrenergic stimulation. Electrical
      pacing in elevated extracellular Ca(2+) ([Ca(2+)](o) = 7 mM) was used to increase
      [Ca(2+)](SR) to the threshold where Ca(2+) waves were consistently observed. The
      beta-adrenergic agonist isoproterenol (ISO; 1 MUM) increased [Ca(2+)](SR) well
      above the control threshold and consistently triggered Ca(2+) waves. However,
      when [Ca(2+)](SR) was subsequently lowered in the presence of ISO (by lowering
      [Ca(2+)](o) to 1 mM and partially inhibiting sarcoplasmic/endoplasmic reticulum
      calcium ATPase with cyclopiazonic acid or thapsigargin), Ca(2+) waves ceased to
      occur at a [Ca(2+)](SR) that was higher than the control threshold. Furthermore,
      for a set [Ca(2+)](SR) level the refractoriness of wave occurrence (Ca(2+) wave
      latency) was prolonged during beta-adrenergic stimulation, and was highly
      dependent on the extent that [Ca](SR) exceeded the wave threshold. These data
      show that acute beta-adrenergic stimulation increases the [Ca(2+)](SR) threshold
      for Ca(2+) waves, and therefore the primary cause of Ca(2+) waves is the robust
      increase in [Ca(2+)](SR) above this higher threshold level. Elevation of the
      [Ca(2+)](SR) wave threshold and prolongation of wave latency represent
      potentially protective mechanisms against pro-arrhythmogenic Ca(2+) release
      during beta-adrenergic stimulation.

PMID- 22988137
TI  - A neurosteroid potentiation site can be moved among GABAA receptor subunits.
AB  - Endogenous neurosteroids are among the most potent and efficacious potentiators
      of activation of GABA(A) receptors. It has been proposed that a conserved
      glutamine residue in the first membrane-spanning region (TM1 region) of the alpha
      subunits is required for binding of potentiating neurosteroids. Mutations of this
      residue can reduce or remove the ability of steroids to potentiate function.
      However, it is not known whether potentiation requires that a steroid interact
      with the alpha subunit, or not. To examine this question we mutated the
      homologous residue in the beta2 and gamma2L subunits to glutamine, and found that
      these mutations could not confer potentiation by allopregnanolone (3alpha5alphaP)
      when expressed in receptors containing ineffective alpha1 subunits. However,
      potentiation is restored when the entire TM1 region from the alpha1 subunit is
      transferred to the beta2 or gamma2L subunit. Mutations in the TM1 region that
      affect potentiation when made in the alpha1 subunit have similar effects when
      made in transferred TM1 region. Further, the effects of 3alpha5alphaP on single
      channel kinetics are similar for wild-type receptors and receptors with moved TM1
      regions. These results support the idea that steroids bind in the transmembrane
      regions of the receptor. The observations are consistent with previous work
      indicating that neurosteroid potentiation is mediated by an action that affects
      the receptor as a whole, rather than an individual subunit or pair of subunits,
      and in addition demonstrate that the mechanism is independent of the nature of
      the subunit that interacts with steroid.

PMID- 22988138
TI  - Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral
      hippocampus.
AB  - The hippocampus has a central role in learning and memory. Although once
      considered a relatively homogenous structure along the longitudinal axis, it has
      become clear that the rodent hippocampus can be anatomically and functionally
      divided into a dorsal component generally associated with spatial navigation, and
      a ventral component primarily associated with non-spatial functions that involve
      an emotional component. The ventral hippocampus (VHC) is also more sensitive to
      epileptogenic stimuli than the dorsal hippocampus (DHC), and seizures tend to
      originate in the VHC before spreading to other brain regions. Although synaptic
      and biochemical differences in DHC and VHC have been investigated, the intrinsic
      excitability of individual neurones from the DHC and VHC has received
      surprisingly little attention. In this study, we have characterized the intrinsic
      electrophysiological properties of CA1 pyramidal neurones from the DHC and the
      VHC using the whole-cell current-clamp method. Our results demonstrate that
      somatic current injections of equal magnitude elicit significantly more action
      potentials in VHC neurones than DHC neurones, and that this difference stems from
      the more depolarized resting membrane potential (RMP; 7 mV) and higher input
      resistance (R(in); 46 M measured from RMP) observed in VHC neurones. These
      differences in RMP and R(in) were also observed in dendritic whole-cell current
      clamp recordings. Furthermore, morphological reconstructions of individual
      neurones revealed significant differences in the dendritic branching pattern
      between DHC and VHC neurones that could, in principle, contribute to the lower
      somatic R(in) of DHC neurones. Together, our results highlight significant
      differences in the intrinsic electrophysiological properties of CA1 pyramidal
      neurones across the longitudinal hippocampal axis, and suggest that VHC neurones
      are intrinsically more excitable than DHC neurones. This difference is likely to
      predispose the VHC to hyperexcitability.

PMID- 22988139
TI  - TARP-associated AMPA receptors display an increased maximum channel conductance
      and multiple kinetically distinct open states.
AB  - Fast excitatory synaptic transmission in the CNS is mediated mainly by AMPA-type
      glutamate receptors (AMPARs), whose biophysical properties are dramatically
      modulated by the presence of transmembrane AMPAR regulatory proteins (TARPs). To
      help construct a kinetic model that will realistically describe native AMPAR/TARP
      function, we have examined the single-channel properties of homomeric GluA1
      AMPARs in combination with the TARPs, gamma-2, gamma-4 and gamma-5. In a
      saturating concentration of agonist, each of these AMPAR/TARP combinations gave
      rise to single-channel currents with multiple conductance levels that appeared
      intrinsic to the receptor-channel complex, and showed long-lived subconductance
      states. The open time and burst length distributions of the receptor complexes
      displayed multiple dwell-time components. In the case of gamma-2- and gamma-4
      associated receptors, these distributions included a long-lived component lasting
      tens of milliseconds that was absent from both GluA1 alone and gamma-5-associated
      receptors. The open time distributions for each conductance level required two
      dwell-time components, indicating that at each conductance level the channel
      occupies a minimum of two kinetically distinct open states. We have explored how
      these data place novel constraints on possible kinetic models of TARP-associated
      AMPARs that may be used to define AMPAR-mediated synaptic transmission.

PMID- 22988140
TI  - Vasodilator interactions in skeletal muscle blood flow regulation.
AB  - During exercise, oxygen delivery to skeletal muscle is elevated to meet the
      increased oxygen demand. The increase in blood flow to skeletal muscle is
      achieved by vasodilators formed locally in the muscle tissue, either on the
      intraluminal or on the extraluminal side of the blood vessels. A number of
      vasodilators have been shown to bring about this increase in blood flow and,
      importantly, interactions between these compounds seem to be essential for the
      precise regulation of blood flow. Two compounds stand out as central in these
      vasodilator interactions: nitric oxide (NO) and prostacyclin. These two
      vasodilators are both stimulated by several compounds, e.g. adenosine, ATP,
      acetylcholine and bradykinin, and are affected by mechanically induced signals,
      such as shear stress. NO and prostacyclin have also been shown to interact in a
      redundant manner where one system can take over when formation of the other is
      compromised. Although numerous studies have examined the role of single and
      multiple pharmacological inhibition of different vasodilator systems, and
      important vasodilators and interactions have been identified, a large part of the
      exercise hyperaemic response remains unexplained. It is plausible that this
      remaining hyperaemia may be explained by cAMP- and cGMP-independent smooth muscle
      relaxation, such as effects of endothelial derived hyperpolarization factors
      (EDHFs) or through metabolic modulation of sympathetic effects. The nature and
      role of EDHF as well as potential novel mechanisms in muscle blood flow
      regulation remain to be further explored to fully elucidate the regulation of
      exercise hyperaemia.

PMID- 22988141
TI  - Association of TMEM16A chloride channel overexpression with airway goblet cell
      metaplasia.
AB  - The TMEM16A protein has a potential role as a Ca(2+)-activated Cl(-) channel
      (CaCC) in airway epithelia where it may be important in the homeostasis of the
      airway surface fluid. We investigated the function and expression of TMEM16A in
      primary human bronchial epithelial cells and in a bronchial cell line (CFBE41o-).
      Under resting conditions, TMEM16A protein expression was relatively low. However,
      TMEM16A silencing with short-interfering RNAs caused a marked inhibition of CaCC
      activity, thus demonstrating that a low TMEM16A expression is sufficient to
      support Ca(2+)-dependent Cl(-) transport. Following treatment for 24-72 h with
      interleukin-4 (IL-4), a cytokine that induces mucous cell metaplasia, TMEM16A
      protein expression was strongly increased in approximately 50% of primary
      bronchial epithelial cells, with a specific localization in the apical membrane.
      IL-4 treatment also increased the percentage of cells expressing MUC5AC, a marker
      of goblet cells. Interestingly, MUC5AC was detected specifically in cells
      expressing TMEM16A. In particular, MUC5AC was found in 15 and 60% of TMEM16A
      positive cells when epithelia were treated with IL-4 for 24 or 72 h,
      respectively. In contrast, ciliated cells showed expression of the cystic
      fibrosis transmembrane conductance regulator Cl(-) channel but not of TMEM16A.
      Our results indicate that TMEM16A protein is responsible for CaCC activity in
      airway epithelial cells, particularly in cells treated with IL-4, and that
      TMEM16A upregulation by IL-4 appears as an early event of goblet cell
      differentiation. These findings suggest that TMEM16A expression is particularly
      required under conditions of mucus hypersecretion to ensure adequate secretion of
      electrolytes and water.

PMID- 22988143
TI  - Inefficient functional sympatholysis is an overlooked cause of malperfusion in
      contracting skeletal muscle.
AB  - Contracting skeletal muscle can overcome sympathetic vasoconstrictor activity
      (functional sympatholysis), which allows for a blood supply that matches the
      metabolic demand. This ability is thought to be mediated by locally released
      substances that modulate the effect of noradrenaline (NA) on the alpha-receptor.
      Tyramine induces local NA release and can be used in humans to investigate the
      underlying mechanisms and physiological importance of functional sympatholysis in
      the muscles of healthy and diseased individuals as well as the impact of the
      active muscles' training status. In sedentary elderly men, functional
      sympatholysis and muscle blood flow are impaired compared to young men, but
      regular physical activity can prevent these age related impairments. In young
      subjects, two weeks of leg immobilization causes a reduced ability for functional
      sympatholysis, whereas the trained leg maintained this function. Patients with
      essential hypertension have impaired functional sympatholysis in the forearm, and
      reduced exercise hyperaemia in the leg, but this can be normalized by aerobic
      exercise training. The effect of physical activity on the local mechanisms that
      modulate sympathetic vasoconstriction is clear, but it remains uncertain which
      locally released substance(s) block the effect of NA and how this is
      accomplished. NO and ATP have been proposed as important inhibitors of NA
      mediated vasoconstriction and presently an inhibitory effect of ATP on NA
      signalling via P2 receptors appears most likely.

PMID- 22988142
TI  - Glycine receptors support excitatory neurotransmitter release in developing mouse
      visual cortex.
AB  - Glycine receptors (GlyRs) are found in most areas of the brain, and their
      dysfunction can cause severe neurological disorders. While traditionally thought
      of as inhibitory receptors, presynaptic-acting GlyRs (preGlyRs) can also
      facilitate glutamate release under certain circumstances, although the underlying
      molecular mechanisms are unknown. In the current study, we sought to better
      understand the role of GlyRs in the facilitation of excitatory neurotransmitter
      release in mouse visual cortex. Using whole-cell recordings, we found that
      preGlyRs facilitate glutamate release in developing, but not adult, visual
      cortex. The glycinergic enhancement of neurotransmitter release in early
      development depends on the high intracellular to extracellular Cl(-) gradient
      maintained by the Na(+)-K(+)-2Cl(-) cotransporter and requires Ca(2+) entry
      through voltage-gated Ca(2+) channels. The glycine transporter 1, localized to
      glial cells, regulates extracellular glycine concentration and the activation of
      these preGlyRs. Our findings demonstrate a developmentally regulated mechanism
      for controlling excitatory neurotransmitter release in the neocortex.

PMID- 22988144
TI  - Impaired mitochondrial respiration and decreased fatigue resistance followed by
      severe muscle weakness in skeletal muscle of mitochondrial DNA mutator mice.
AB  - Mitochondrial dysfunction can drastically impair muscle function, with weakness
      and exercise intolerance as key symptoms. Here we examine the time course of
      development of muscle dysfunction in a mouse model of premature ageing induced by
      defective proofreading function of mitochondrial DNA (mtDNA) polymerase (mtDNA
      mutator mouse). Isolated fast-twitch muscles and single muscle fibres from young
      (3-5 months) and end-stage (11 months) mtDNA mutator mice were compared to age
      matched control mice. Force and free myoplasmic [Ca(2+)] ([Ca(2+)](i)) were
      measured under resting conditions and during fatigue induced by repeated tetani.
      Muscles of young mtDNA mutator mice displayed no weakness in the rested state,
      but had lower force and [Ca(2+)](i) than control mice during induction of
      fatigue. Muscles of young mtDNA mutator mice showed decreased activities of
      citrate synthase and beta-hydroxyacyl-coenzyme A dehydrogenase, reduced
      expression of cytochrome c oxidase, and decreased expression of triggers of
      mitochondrial biogenesis (PGC-1alpha, PPARalpha, AMPK). Muscles from end-stage
      mtDNA mutator mice showed weakness under resting conditions with markedly
      decreased tetanic [Ca(2+)](i), force per cross-sectional area and protein
      expression of the sarcoplasmic reticulum Ca(2+) pump (SERCA1). In conclusion,
      fast-twitch muscles of prematurely ageing mtDNA mutator mice display a sequence
      of deleterious mitochondrial-to-nucleus signalling with an initial decrease in
      oxidative capacity, which was not counteracted by activation of signalling to
      increase mitochondrial biogenesis. This was followed by severe muscle weakness in
      the end stage. These results have implication for normal ageing and suggest that
      decreased mitochondrial oxidative capacity due to a sedentary lifestyle may
      predispose towards muscle weakness developing later in life.

PMID- 22988146
TI  - Infectious disease experts monitor outbreaks of enterovirus 71 in Asia.

PMID- 22988145
TI  - Facilitation of cytosolic calcium wave propagation by local calcium uptake into
      the sarcoplasmic reticulum in cardiac myocytes.
AB  - The widely accepted paradigm for cytosolic Ca(2+) wave propagation postulates a
      'fire-diffuse-fire' mechanism where local Ca(2+)-induced Ca(2+) release (CICR)
      from the sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) Ca(2+) release
      channels diffuses towards and activates neighbouring release sites, resulting in
      a propagating Ca(2+) wave. A recent challenge to this paradigm proposed the
      requirement for an intra-SR 'sensitization' Ca(2+) wave that precedes the
      cytosolic Ca(2+) wave and primes RyRs from the luminal side to CICR. Here, we
      tested this hypothesis experimentally with direct simultaneous measurements of
      cytosolic ([Ca(2+)](i); rhod-2) and intra-SR ([Ca(2+)](SR); fluo-5N) calcium
      signals during wave propagation in rabbit ventricular myocytes, using high
      resolution fluorescence confocal imaging. The increase in [Ca(2+)](i) at the wave
      front preceded depletion of the SR at each point along the calcium wave front,
      while during this latency period a transient increase of [Ca(2+)](SR) was
      observed. This transient elevation of [Ca(2+)](SR) could be identified at
      individual release junctions and depended on the activity of the sarco
      endoplasmic reticulum Ca(2+)-ATPase (SERCA). Increased SERCA activity (beta
      adrenergic stimulation with 1 MUM isoproterenol (isoprenaline)) decreased the
      latency period and increased the amplitude of the transient elevation of
      [Ca(2+)](SR), whereas inhibition of SERCA (3 MUM cyclopiazonic acid) had the
      opposite effect. In conclusion, the data provide experimental evidence that local
      Ca(2+) uptake by SERCA into the SR facilitates the propagation of cytosolic
      Ca(2+) waves via luminal sensitization of the RyR, and supports a novel paradigm
      of a 'fire-diffuse-uptake-fire' mechanism for Ca(2+) wave propagation in cardiac
      myocytes.

PMID- 22988148
TI  - Adequate sleep to improve the treatment of obesity.

PMID- 22988147
TI  - Constipation and poor feeding in an infant with botulism.

PMID- 22988152
TI  - One last nail in the MAPLEs coffin.

PMID- 22988154
TI  - Free medicine for all in India.

PMID- 22988153
TI  - Diagnosing borderline personality disorder.

PMID- 22988155
TI  - Protecting our most vulnerable elders from abuse.

PMID- 22988156
TI  - Bier spots.

PMID- 22988157
TI  - Tackling immobility in hospitalized seniors.

PMID- 22988158
TI  - Risk of cancer among patients with herpes zoster infection: a population-based
      study.
AB  - BACKGROUND: Whether the risk of cancer is increased among patients with herpes
      zoster is unclear. We investigated the risk of cancer among patients with herpes
      zoster using a nationwide health registry in Taiwan. METHODS: We identified 35
      871 patients with newly diagnosed herpes zoster during 2000-2008 from the
      National Health Insurance Research Database in Taiwan. We analyzed the
      standardized incidence ratios for various types of cancer. RESULTS: Among
      patients with herpes zoster, 895 cases of cancer were reported. Patients with
      herpes zoster were not at increased risk of cancer (standardized incidence ratio
      0.99, 95% confidence interval 0.93-1.06). Among the subgroups stratified by sex,
      age and years of follow-up, there was also no increased risk of overall cancer.
      INTERPRETATION: Herpes zoster is not associated with increased risk of cancer in
      the general population. These findings do not support extensive investigations
      for occult cancer or enhanced surveillance for cancer in patients with herpes
      zoster.

PMID- 22988234
TI  - Isozyme-specific interaction of protein kinase Cdelta with mitochondria dissected
      using live cell fluorescence imaging.
AB  - PKCdelta signaling to mitochondria has been implicated in both mitochondrial
      apoptosis and metabolism. However, the mechanism by which PKCdelta interacts with
      mitochondria is not well understood. Using FRET-based imaging, we show that
      PKCdelta interacts with mitochondria by a novel and isozyme-specific mechanism
      distinct from its canonical recruitment to other membranes such as the plasma
      membrane or Golgi. Specifically, we show that PKCdelta interacts with
      mitochondria following stimulation with phorbol esters or, in L6 myocytes, with
      insulin via a mechanism that requires two steps. In the first step, PKCdelta
      translocates acutely to mitochondria by a mechanism that requires its C1A and C1B
      domains and a Leu-Asn sequence in its turn motif. In the second step, PKCdelta is
      retained at mitochondria by a mechanism that depends on its C2 domain, a unique
      Glu residue in its activation loop, intrinsic catalytic activity, and the
      mitochondrial membrane potential. In contrast, of these determinants, only the
      C1B domain is required for the phorbol ester-stimulated translocation of PKCdelta
      to other membranes. PKCdelta also basally localizes to mitochondria and increases
      mitochondrial respiration via many of the same determinants that promote its
      agonist-evoked interaction. PKCdelta localized to mitochondria has robust
      activity, as revealed by a FRET reporter of PKCdelta-specific activity
      (deltaCKAR). These data support a model in which multiple determinants unique to
      PKCdelta drive a specific interaction with mitochondria that promotes
      mitochondrial respiration.

PMID- 22988235
TI  - Inhibition of paclitaxel-induced decreases in calcium signaling.
AB  - Peripheral neuropathy is one of the most severe and irreversible side effects
      caused by treatment from several chemotherapeutic drugs, including paclitaxel
      (Taxol(r)) and vincristine. Strategies are needed that inhibit this unwanted side
      effect without altering the chemotherapeutic action of these drugs. We previously
      identified two proteins in the cellular pathway that lead to Taxol-induced
      peripheral neuropathy, neuronal calcium sensor-1 (NCS-1) and calpain. Prolonged
      treatment with Taxol induces activation of calpain, degradation of NCS-1, and
      loss of intracellular calcium signaling. This paper has focused on understanding
      the molecular basis for prevention of peripheral neuropathy by testing the
      effects of addition of two candidate compounds to the existing chemotherapeutic
      drug regime: lithium and ibudilast. We found that the co-administration of either
      lithium or ibudilast to neuroblastoma cells that were treated with Taxol or
      vincristine inhibited activation of calpain and the reductions in NCS-1 levels
      and calcium signaling associated with these chemotherapeutic drugs. The ability
      of Taxol to alter microtubule formation was unchanged by the addition of either
      candidate compound. These results allow us to suggest that it is possible to
      prevent the unnecessary and irreversible damage caused by chemotherapeutic drugs
      while still maintaining therapeutic efficacy. Specifically, the addition of
      either lithium or ibudilast to existing chemotherapy treatment protocols has the
      potential to prevent chemotherapy-induced peripheral neuropathy.

PMID- 22988236
TI  - Vascular bioactivation of nitroglycerin by aldehyde dehydrogenase-2: reaction
      intermediates revealed by crystallography and mass spectrometry.
AB  - Aldehyde dehydrogenase-2 (ALDH2) catalyzes the bioactivation of nitroglycerin
      (glyceryl trinitrate, GTN) in blood vessels, resulting in vasodilation by nitric
      oxide (NO) or a related species. Because the mechanism of this reaction is still
      unclear we determined the three-dimensional structures of wild-type (WT) ALDH2
      and of a triple mutant of the protein that exhibits low denitration activity
      (E268Q/C301S/C303S) in complex with GTN. The structure of the triple mutant
      showed that GTN binds to the active site via polar contacts to the oxyanion hole
      and to residues 268 and 301 as well as by van der Waals interactions to
      hydrophobic residues of the catalytic pocket. The structure of the GTN-soaked
      wild-type protein revealed a thionitrate adduct to Cys-302 as the first reaction
      intermediate, which was also found by mass spectrometry (MS) experiments. In
      addition, the MS data identified sulfinic acid as the irreversibly inactivated
      enzyme species. Assuming that the structures of the triple mutant and wild-type
      ALDH2 reflect binding of GTN to the catalytic site and the first reaction step,
      respectively, superposition of the two structures indicates that denitration of
      GTN is initiated by nucleophilic attack of Cys-302 at one of the terminal nitrate
      groups, resulting in formation of the observed thionitrate intermediate and
      release of 1,2-glyceryl dinitrate. Our results shed light on the molecular
      mechanism of the GTN denitration reaction and provide useful information on the
      structural requirements for high affinity binding of organic nitrates to the
      catalytic site of ALDH2.

PMID- 22988237
TI  - Inhibition of microRNA-302 (miR-302) by bone morphogenetic protein 4 (BMP4)
      facilitates the BMP signaling pathway.
AB  - The signaling pathway mediated by BMPs plays an essential role during development
      as well as the maintenance of homeostasis in adult. Aberrant activation or
      inactivation of BMP signaling can lead to developmental defects and various human
      disorders. To fine-tune its activity, BMP signaling is regulated both positively
      and negatively by extrinsic and intrinsic regulatory factors that modulate
      binding of ligand to the receptors, and the activity of receptors and their
      dedicated signal transducers, the Smad proteins. Upon BMP binding to the receptor
      complex, Smad proteins translocate to the nucleus and modulate gene expression
      transcriptionally by directly associating with the promoter region of target
      genes, or post-transcriptionally through modulation of microRNA (miRNA)
      synthesis. In this study, we demonstrate that BMP signaling down-regulates
      transcription of the miRNA-302~367 gene cluster. We show that the type II BMP
      receptor (BMPRII) is a novel target of miR-302. Upon overexpression, miR-302
      targets a partially complementary sequence localized in the 3'-untranslated
      region (UTR) of BMPRII transcripts and leads to destabilization of the
      transcripts and down-regulation of BMP signaling. We propose that the negative
      regulatory loop of BMP4-miR-302-BMPRII is a potential mechanism for the
      maintenance and fine-tuning of the BMP signaling pathway in various systems.

PMID- 22988238
TI  - Activation of NF-kappaB protein prevents the transition from juvenile ovary to
      testis and promotes ovarian development in zebrafish.
AB  - Testis differentiation in zebrafish involves juvenile ovary to testis
      transformation initiated by an apoptotic wave. The molecular regulation of this
      transformation process is not fully understood. NF-kappaB is activated at an
      early stage of development and has been shown to interact with steroidogenic
      factor-1 in mammals, leading to the suppression of anti-Mullerian hormone (Amh)
      gene expression. Because steroidogenic factor-1 and Amh are important for proper
      testis development, NF-kappaB-mediated induction of anti-apoptotic genes could,
      therefore, also play a role in zebrafish gonad differentiation. The aim of this
      study was to examine the potential role of NF-kappaB in zebrafish gonad
      differentiation. Exposure of juvenile zebrafish to heat-killed Escherichia coli
      activated the NF-kappaB pathways and resulted in an increased ratio of females
      from 30 to 85%. Microarray and quantitative real-time-PCR analysis of gonads
      showed elevated expression of NF-kappaB-regulated genes. To confirm the
      involvement of NF-kappaB-induced anti-apoptotic effects, zebrafish were treated
      with sodium deoxycholate, a known inducer of NF-kappaB or NF-kappaB activation
      inhibitor (NAI). Sodium deoxycholate treatment mimicked the effect of heat-killed
      bacteria and resulted in an increased proportion of females from 25 to 45%,
      whereas the inhibition of NF-kappaB using NAI resulted in a decrease in females
      from 45 to 20%. This study provides proof for an essential role of NF-kappaB in
      gonadal differentiation of zebrafish and represents an important step toward the
      complete understanding of the complicated process of sex differentiation in this
      species and possibly other cyprinid teleosts as well.

PMID- 22988239
TI  - Combined effects of agitation, macromolecular crowding, and interfaces on
      amyloidogenesis.
AB  - Amyloid formation and accumulation is a hallmark of protein misfolding diseases
      and is associated with diverse pathologies including type II diabetes and
      Alzheimer's disease (AD). In vitro, amyloidogenesis is widely studied in
      conditions that do not simulate the crowded and viscous in vivo environment. A
      high volume fraction of most biological fluids is occupied by various
      macromolecules, a phenomenon known as macromolecular crowding. For some amyloid
      systems (e.g. alpha-synuclein) and under shaking condition, the excluded volume
      effect of macromolecular crowding favors aggregation, whereas increased viscosity
      reduces the kinetics of these reactions. Amyloidogenesis can also be catalyzed by
      hydrophobic-hydrophilic interfaces, represented by the air-water interface in
      vitro and diverse heterogeneous interfaces in vivo (e.g. membranes). In this
      study, we investigated the effects of two different crowding polymers (dextran
      and Ficoll) and two different experimental conditions (with and without shaking)
      on the fibrilization of amyloid-beta peptide, a major player in AD pathogenesis.
      Specifically, we demonstrate that, during macromolecular crowding, viscosity
      dominates over the excluded volume effect only when the system is spatially non
      homogeneous (i.e. an air-water interface is present). We also show that the
      surfactant activity of the crowding agents can critically influence the outcome
      of macromolecular crowding and that the structure of the amyloid species formed
      may depend on the polymer used. This suggests that, in vivo, the outcome of
      amyloidogenesis may be affected by both macromolecular crowding and spatial
      heterogeneity (e.g. membrane turn-over). More generally, our work suggests that
      any factors causing changes in crowding may be susceptibility factors in AD.

PMID- 22988240
TI  - beta-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1)-deficient
      mice exhibit a close homolog of L1 (CHL1) loss-of-function phenotype involving
      axon guidance defects.
AB  - BACE1 is the beta-secretase enzyme that initiates production of the beta-amyloid
      peptide involved in Alzheimer disease. However, little is known about the
      functions of BACE1. BACE1-deficient mice exhibit mild but complex neurological
      phenotypes suggesting therapeutic BACE1 inhibition may not be completely free of
      mechanism-based side effects. Recently, we have reported that BACE1 null mice
      have axon guidance defects in olfactory sensory neuron projections to glomeruli
      in the olfactory bulb. Here, we show that BACE1 deficiency also causes an axon
      guidance defect in the hippocampus, a shortened and disorganized infrapyramidal
      bundle of the mossy fiber projection from the dentate gyrus to CA3. Although we
      observed that a classical axon guidance molecule, EphA4, was cleaved by BACE1
      when co-expressed with BACE1 in HEK293 cells, we could find no evidence of BACE1
      processing of EphA4 in the brain. Remarkably, we discovered that the axon
      guidance defects of BACE1(-/-) mice were strikingly similar to those of mice
      deficient in a recently identified BACE1 substrate, the neural cell adhesion
      molecule close homolog of L1 (CHL1) that is involved in neurite outgrowth. CHL1
      undergoes BACE1-dependent processing in BACE1(+/+), but not BACE1(-/-),
      hippocampus, and olfactory bulb, indicating that CHL1 is a BACE1 substrate in
      vivo. Finally, BACE1 and CHL1 co-localize in the terminals of hippocampal mossy
      fibers, olfactory sensory neuron axons, and growth cones of primary hippocampal
      neurons. We conclude that BACE1(-/-) axon guidance defects are likely the result
      of abrogated BACE1 processing of CHL1 and that BACE1 deficiency produces a CHL1
      loss-of-function phenotype. Our results imply the possibility that axon mis
      targeting may occur in adult neurogenic and/or regenerating neurons as a result
      of chronic BACE1 inhibition and add a note of caution to BACE1 inhibitor
      development.

PMID- 22988241
TI  - The regulatory mechanism of the LY6K gene expression in human breast cancer
      cells.
AB  - LY6K is a cancer biomarker and a therapeutic target that induces invasion and
      metastasis. However, the molecular mechanisms that determine human LY6K
      transcription are completely unknown. To elucidate the mechanisms involved in
      human LY6K gene regulation and expression, multiple cis-elements were predicted
      using TRANSFAC software, and the LY6K regulatory region was identified using the
      luciferase assay in the human LY6K gene promoter. We performed ChIP, EMSA, and
      supershift assays to investigate the transcription factor activity on the LY6K
      promoter, and the effect of a SNP and CpG site methylation on AP-1 transcription
      factor binding affinity. AP-1 and the CREB transcription factor bound to LY6K
      promoter within -550/-1, which was essential for LY6K expression, but only the AP
      1 heterodimer, JunD, and Fra-1, modulates LY6K gene transcriptional level. A
      decrease in LY6K was associated with the SNP242 C allele, a polymorphic G/C-SNP
      at the 242 nucleotide in the LY6K promoter region (rs2585175), or methylation of
      the CpG site, which was closely located with the AP-1 site by interfering with
      binding of the AP-1 transcription factor to the LY6K promoter. Our findings
      reveal an important role for AP-1 activation in promoting LY6K gene expression
      that regulates cell mobility of breast cancer cells, whereas the SNP242 C allele
      or methylation of the CpG site may reduce the risk of invasion or metastasis by
      interfering AP-1 activation.

PMID- 22988242
TI  - A 22-mer segment in the structurally pliable regulatory domain of metazoan CTP:
      phosphocholine cytidylyltransferase facilitates both silencing and activating
      functions.
AB  - CTP:phosphocholine cytidylyltransferase (CCT), an amphitropic enzyme that
      regulates phosphatidylcholine synthesis, is composed of a catalytic head domain
      and a regulatory tail. The tail region has dual functions as a regulator of
      membrane binding/enzyme activation and as an inhibitor of catalysis in the
      unbound form of the enzyme, suggesting conformational plasticity. These functions
      are well conserved in CCTs across diverse phyla, although the sequences of the
      tail regions are not. CCT regulatory tails of diverse origins are composed of a
      long membrane lipid-inducible amphipathic helix (m-AH) followed by a highly
      disordered segment, reminiscent of the Parkinson disease-linked protein, alpha
      synuclein, which we show shares a novel sequence motif with vertebrate CCTs. To
      unravel features required for silencing, we created chimeric enzymes by fusing
      the catalytic domain of rat CCTalpha to the regulatory tail of CCTs from
      Drosophila, Caenorhabditis elegans, or Saccharomyces cerevisiae or to alpha
      synuclein. Only the tail domains of the two invertebrate CCTs were competent for
      both suppression of catalytic activity and for activation by lipid vesicles.
      Thus, both silencing and activating functions of the m-AH can tolerate
      significant changes in length and sequence. We identified a highly amphipathic 22
      residue segment in the m-AH with features conserved among animal CCTs but not
      yeast CCT or alpha-synuclein. Deletion of this segment from rat CCT increased the
      lipid-independent V(max) by 10-fold, equivalent to the effect of deleting the
      entire tail, and severely weakened membrane binding affinity. However, membrane
      binding was required for additional increases in catalytic efficiency. Thus, full
      activation of CCT may require not only loss of a silencing conformation in the m
      AH but a gain of an activating conformation, promoted by membrane binding.

PMID- 22988243
TI  - Malectin forms a complex with ribophorin I for enhanced association with
      misfolded glycoproteins.
AB  - Malectin is an endoplasmic reticulum-resident lectin, which recognizes di
      glucosylated Glc(2)Man(9)GlcNAc(2) (G2M9) N-glycans on newly synthesized
      glycoproteins. We previously demonstrated that malectin preferentially associates
      with misfolded glycoproteins and inhibits their secretion (Chen, Y., Hu, D.,
      Yabe, R., Tateno, H., Qin, S. Y., Matsumoto, N., Hirabayashi, J., and Yamamoto,
      K. (2011) Mol. Biol. Cell 22, 3559-3570). The sugar binding activity of malectin
      is required for this process. However, because G2M9 N-glycans are generated at
      the very early stage of processing and are typically found on both misfolded
      glycoproteins and glycoproteins undergoing folding, other mechanisms must
      underlie the preference of malectin for misfolded glycoproteins. Here, we
      searched for proteins that were co-immunoprecipitated with malectin, and we found
      that malectin formed a stable complex with an endoplasmic reticulum-resident
      transmembrane protein, ribophorin I. Co-expression of malectin and ribophorin I
      significantly enhanced the association between malectin and a folding-defective
      alpha1-antitrypsin variant (null Hong Kong) and reduced its secretion; however,
      secretion of wild-type alpha1-antitrypsin was not affected. The enhanced
      association and reduced secretion were counteracted by siRNA-mediated down
      regulation of ribophorin I. Also, a reporter assay revealed that ribophorin I
      preferentially interacted with misfolded ribonuclease A but not with the native
      form, suggesting that ribophorin I may function as a chaperone that recognizes
      misfolded proteins inside cells. These results provide the first evidence of the
      mechanism by which malectin preferentially associates with misfolded
      glycoproteins.

PMID- 22988244
TI  - Glycosyltransferase-specific Golgi-targeting mechanisms.
AB  - Glycosylation of secreted and membrane-bound mucins is carried out by
      glycosyltransferases localized to specific Golgi compartments according to the
      step in which each enzyme participates. However, the Golgi-targeting mechanisms
      of these enzymes are not clear. Herein, we investigate the Golgi-targeting
      mechanisms of core 1 beta3 galactosyltransferase (C1GalT1) and core 2 beta1,6-N
      acetylglucosaminyltransferase-2 or mucus type (C2GnT-M), which participate in the
      early O-glycosylation steps. siRNAs, co-immunoprecipitation, and confocal
      fluorescence microscopy were employed to identify the golgins involved in the
      Golgi docking of vesicular complexes (VCs) that carry these two enzymes. We have
      found that these VCs use different golgins for docking: C2GnT-M-carrying VC
      (C2GnT-M-VC) utilizes Giantin, whereas C1GalT1-VC employs GM130-GRASP65 complex.
      However, in the absence of GRASP65, C1GalT1-VC utilizes GM130-Giantin complex.
      Also, we have found that these VCs are 1.1-1.2 MUm in diameter, specific for each
      enzyme, and independent of coat protein complex II and I (COPII and COPI). These
      two fluorescently tagged enzymes exhibit different fluorescence recovery times in
      the Golgi after photobleaching. Thus, novel enzyme-specific Golgi-targeting
      mechanisms are employed by glycosyltransferases, and multiple Golgi docking
      strategies are utilized by C1GalT1.

PMID- 22988245
TI  - The kelch protein KLHDC8B guards against mitotic errors, centrosomal
      amplification, and chromosomal instability.
AB  - The malignant cell in classical Hodgkin lymphoma (HL) is the binucleated giant
      Reed-Sternberg cell. Chromosomal instability and mitotic errors may contribute to
      HL pathogenesis; one potential mitotic regulator is the kelch protein KLHDC8B,
      which localizes to the midbody, is expressed during mitosis, and is mutated in a
      subset of familial and sporadic HL. We report that disrupting KLHDC8B function in
      HeLa cells, B lymphoblasts, and fibroblasts leads to significant increases in
      multinucleation, multipolar mitoses, failed abscission, asymmetric segregation of
      daughter nuclei, formation of anucleated daughter cells, centrosomal
      amplification, and aneuploidy. We recapitulated the major pathologic features of
      the Reed-Sternberg cell and concluded that KLHDC8B is essential for mitotic
      integrity and maintenance of chromosomal stability. The significant impact of
      KLHDC8B implicates the central roles of mitotic regulation and chromosomal
      segregation in the pathogenesis of HL and provides a novel molecular mechanism
      for chromosomal instability in HL.

PMID- 22988246
TI  - Starch source influences dietary glucose generation at the mucosal alpha
      glucosidase level.
AB  - The quality of starch digestion, related to the rate and extent of release of
      dietary glucose, is associated with glycemia-related problems such as diabetes
      and other metabolic syndrome conditions. Here, we found that the rate of glucose
      generation from starch is unexpectedly associated with mucosal alpha-glucosidases
      and not just alpha-amylase. This understanding could lead to a new approach to
      regulate the glycemic response and glucose-related physiologic responses in the
      human body. There are six digestive enzymes for starch: salivary and pancreatic
      alpha-amylases and four mucosal alpha-glucosidases, including N- and C-terminal
      subunits of both maltase-glucoamylase and sucrase-isomaltase. Only the mucosal
      alpha-glucosidases provide the final hydrolytic activities to produce substantial
      free glucose. We report here the unique and shared roles of the individual alpha
      glucosidases for alpha-glucans persisting after starch is extensively hydrolyzed
      by alpha-amylase (to produce alpha-limit dextrins (alpha-LDx)). All four alpha
      glucosidases share digestion of linear regions of alpha-LDx, and three can
      hydrolyze branched fractions. The alpha-LDx, which were derived from different
      maize cultivars, were not all equally digested, revealing that the starch source
      influences glucose generation at the mucosal alpha-glucosidase level. We further
      discovered a fraction of alpha-LDx that was resistant to the extensive digestion
      by the mucosal alpha-glucosidases. Our study further challenges the conventional
      view that alpha-amylase is the only rate-determining enzyme involved in starch
      digestion and better defines the roles of individual and collective mucosal alpha
      glucosidases. Strategies to control the rate of glucogenesis at the mucosal level
      could lead to regulation of the glycemic response and improved glucose management
      in the human body.

PMID- 22988247
TI  - Identification of novel alpha1,3-galactosyltransferase and elimination of alpha
      galactose-containing glycans by disruption of multiple alpha
      galactosyltransferase genes in Schizosaccharomyces pombe.
AB  - The oligosaccharides from fission yeast Schizosaccharomyces pombe contain large
      amounts of D-galactose (Gal) in addition to D-mannose (Man), in contrast to the
      budding yeast Saccharomyces cerevisiae. Detailed structural analysis has revealed
      that the Gal residues are attached to the N- and O-linked oligosaccharides via
      alpha1,2- or alpha1,3-linkages. Previously we constructed and characterized a
      septuple alpha-galactosyltransferase disruptant (7GalTDelta) anticipating a
      complete lack of alpha-Gal residues. However, the 7GalTDelta strain still
      contained oligosaccharides consisting of alpha1,3-linked Gal residues, indicating
      the presence of at least one more additional unidentified alpha1,3
      galactosyltransferase. In this study we searched for unidentified putative
      glycosyltransferases in the S. pombe genome sequence and identified three novel
      genes, named otg1(+)-otg3(+) (alpha one, three-galactosyltransferase), that
      belong to glycosyltransferase gene family 8 in the Carbohydrate Active EnZymes
      (CAZY) database. Gal-recognizing lectin blotting and HPLC analyses of
      pyridylaminated oligosaccharides after deletion of these three additional genes
      from 7GalTDelta strain demonstrated that the resultant disruptant missing 10
      alpha-galactosyltransferase genes, 10GalTDelta, exhibited a complete loss of
      galactosylation. In an in vitro galactosylation assay, the otg2(+) gene product
      had Gal transfer activity toward a pyridylaminated Man(9)GlcNAc(2)
      oligosaccharide and pyridylaminated Manalpha1,2-Manalpha1,2-Man oligosaccharide.
      In addition, the otg3(+) gene product exhibited Gal transfer activity toward the
      pyridylaminated Man(9)GlcNAc(2) oligosaccharide. Generation of an alpha1,3
      linkage was confirmed by HPLC analysis, alpha-galactosidase digestion analysis,
      (1)H NMR spectroscopy, and LC-MS/MS analysis. These results indicate that Otg2p
      and Otg3p are involved in alpha1,3-galactosylation of S. pombe oligosaccharides.

PMID- 22988248
TI  - Versatile high resolution oligosaccharide microarrays for plant glycobiology and
      cell wall research.
AB  - Microarrays are powerful tools for high throughput analysis, and hundreds or
      thousands of molecular interactions can be assessed simultaneously using very
      small amounts of analytes. Nucleotide microarrays are well established in plant
      research, but carbohydrate microarrays are much less established, and one reason
      for this is a lack of suitable glycans with which to populate arrays.
      Polysaccharide microarrays are relatively easy to produce because of the ease of
      immobilizing large polymers noncovalently onto a variety of microarray surfaces,
      but they lack analytical resolution because polysaccharides often contain
      multiple distinct carbohydrate substructures. Microarrays of defined
      oligosaccharides potentially overcome this problem but are harder to produce
      because oligosaccharides usually require coupling prior to immobilization. We
      have assembled a library of well characterized plant oligosaccharides produced
      either by partial hydrolysis from polysaccharides or by de novo chemical
      synthesis. Once coupled to protein, these neoglycoconjugates are versatile
      reagents that can be printed as microarrays onto a variety of slide types and
      membranes. We show that these microarrays are suitable for the high throughput
      characterization of the recognition capabilities of monoclonal antibodies,
      carbohydrate-binding modules, and other oligosaccharide-binding proteins of
      biological significance and also that they have potential for the
      characterization of carbohydrate-active enzymes.

PMID- 22988250
TI  - Mechanisms for kinase-mediated dimerization of the epidermal growth factor
      receptor.
AB  - We study a mechanism by which dimerization of the EGF receptor (EGFR) cytoplasmic
      domain is transmitted to the ectodomain. Therapeutic and other small molecule
      antagonists to the kinase domain that stabilize its active conformation, but not
      those that stabilize an inactive conformation, stabilize ectodomain dimerization.
      Inhibitor-induced dimerization requires an asymmetric kinase domain interface
      associated with activation. EGF and kinase inhibitors stimulate formation of
      identical dimer interfaces in the EGFR transmembrane domain, as shown by
      disulfide cross-linking. Disulfide cross-linking at an interface in domain IV in
      the ectodomain was also stimulated similarly; however, EGF but not inhibitors
      stimulated cross-linking in domain II. Inhibitors similarly induced noncovalent
      dimerization in nearly full-length, detergent-solubilized EGFR as shown by gel
      filtration. EGFR ectodomain deletion resulted in spontaneous dimerization,
      whereas deletion of exons 2-7, in which extracellular domains III and IV are
      retained, did not. In EM, kinase inhibitor-induced dimers lacked any well defined
      orientation between the ectodomain monomers. Fab of the therapeutic antibody
      cetuximab to domain III confirmed a variable position and orientation of this
      domain in inhibitor-induced dimers but suggested that the C termini of domain IV
      of the two monomers were in close proximity, consistent with dimerization in the
      transmembrane domains. The results provide insights into the relative energetics
      of intracellular and extracellular dimerization in EGFR and have significance for
      physiologic dimerization through the asymmetric kinase interface, bidirectional
      signal transmission in EGFR, and mechanism of action of therapeutics.

PMID- 22988249
TI  - Regulation of glycan structures in murine embryonic stem cells: combined
      transcript profiling of glycan-related genes and glycan structural analysis.
AB  - The abundance and structural diversity of glycans on glycoproteins and
      glycolipids are highly regulated and play important roles during vertebrate
      development. Because of the challenges associated with studying glycan regulation
      in vertebrate embryos, we have chosen to study mouse embryonic stem (ES) cells as
      they differentiate into embryoid bodies (EBs) or into extraembryonic endodermal
      (ExE) cells as a model for cellular differentiation. We profiled N- and O-glycan
      structures isolated from these cell populations and examined transcripts encoding
      the corresponding enzymatic machinery for glycan biosynthesis in an effort to
      probe the mechanisms that drive the regulation of glycan diversity. During
      differentiation from mouse ES cells to either EBs or ExE cells, general trends
      were detected. The predominance of high mannose N-glycans in ES cells shifted to
      an equal abundance of complex and high mannose structures, increased sialylation,
      and increased alpha-Gal termination in the differentiated cell populations.
      Whereas core 1 O-glycan structures predominated in all three cell populations,
      increased sialylation and increased core diversity characterized the O-glycans of
      both differentiated cell types. Increased polysialylation was also found in both
      differentiated cell types. Differences between the two differentiated cell types
      included greater sialylation of N-glycans in EBs, whereas alpha-Gal-capped
      structures were more prevalent in ExE cells. Changes in glycan structures
      generally, but not uniformly, correlated with alterations in transcript abundance
      for the corresponding biosynthetic enzymes, suggesting that transcriptional
      regulation contributes significantly to the regulation of glycan expression.
      Knowledge of glycan structural diversity and transcript regulation should provide
      greater understanding of the roles of protein glycosylation in vertebrate
      development.

PMID- 22988251
TI  - Translational control of protein synthesis: the early years.
AB  - For the past fifty-five years, much of my research has focused on the function
      and biogenesis of red blood cells, including the cloning and study of many
      membrane proteins such as glucose and anion transporters and the erythropoietin
      receptor. We have also elucidated the mechanisms of membrane insertion, folding,
      and maturation of many plasma membrane and secreted proteins. Despite all of this
      work and more, I remain extremely proud of our very early work on the regulation
      of mRNA translation: work on bacteriophage f2 RNA in the 1960s and on translation
      of alpha- and beta-globin mRNAs in the early 1970s. Using techniques hopelessly
      antiquated by today's standards, we correctly elucidated many important aspects
      of translational control, and I thought readers would be interested in learning
      how we did these experiments.

PMID- 22988252
TI  - Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage
      migration inhibitory factor (MIF) family members in non-small cell lung
      carcinomas.
AB  - AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing
      enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage
      migration inhibitory factor (MIF) and its functional homolog, d-dopachrome
      tautomerase (d-DT), have protumorigenic functions in non-small cell lung
      carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell
      types, we set out to investigate this apparent paradox. Our data now suggest
      that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed
      cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and
      activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our
      data further indicate that MIF and d-DT, acting through their shared cell surface
      receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake,
      ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin
      dependent kinase kinase beta-dependent AMPK activation. Combined, these studies
      indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1
      independent manner.

PMID- 22988254
TI  - A multivalent three-point linkage analysis model of autotetraploids.
AB  - Because of its widespread occurrence and role in shaping evolutionary processes
      in the biological kingdom, especially in plants, polyploidy has been increasingly
      studied from cytological to molecular levels. By inferring gene order, gene
      distances and gene homology, linkage mapping with molecular markers has proven
      powerful for investigating genome structure and organization. Here we review and
      assess a general statistical model for three-point linkage analysis in
      autotetraploids by integrating double reduction, a phenomenon that commonly
      occurs in autopolyploids whose chromosomes are derived from a single ancestral
      species. This model does not require any assumption on the distribution of the
      occurrence of double reduction and can handle the complexity of multilocus
      linkage in terms of crossover interference. Implemented with the expectation
      maximization (EM) algorithms, the model can estimate and test the recombination
      fractions between less informative dominant markers, thus facilitating its
      practical implications for any autopolyploids in most of which inexpensive
      dominant markers are still used for their genetic and evolutionary studies. The
      model was applied to reanalyze a published data in tetraploid switchgrass,
      validating its practical usefulness and utilization. 

PMID- 22988253
TI  - Intracellular and extracellular ATP coordinately regulate the inverse correlation
      between osteoclast survival and bone resorption.
AB  - Osteoclasts, highly differentiated bone-resorbing cells of hematopoietic origin,
      have two conflicting tendencies: a lower capacity to survive and a higher
      capacity to execute energy-consuming activities such as bone resorption. Here, we
      report that when compared with their precursors, mature mitochondria-rich
      osteoclasts have lower levels of intracellular ATP, which is associated with
      receptor activator of nuclear factor kappa-B ligand (RANKL)-induced Bcl-x(L) down
      regulation. Severe ATP depletion, caused by disrupting mitochondrial
      transcription factor A (Tfam) gene, leads to increased bone-resorbing activity
      despite accelerated apoptosis. Although AMP-activated protein kinase (AMPK)
      activation by ATP depletion is not involved in the regulation of osteoclast
      function, the release of ATP from intracellular stores negatively regulates bone
      resorbing activity through an autocrine/paracrine feedback loop by altering
      cytoskeletal structures. Furthermore, osteoclasts derived from aged mice exhibit
      reduced mitochondrial DNA (mtDNA) and intracellular ATP levels with increased
      bone-resorbing activity, implicating the possible involvement of age-related
      mitochondrial dysfunction in osteoporosis. Thus, our study provides evidence for
      a mechanism underlying the control of cellular functions by reciprocal changes in
      intracellular and extracellular ATP, which regulate the negative correlation
      between osteoclast survival and bone resorption.

PMID- 22988255
TI  - Developing an online programme in computational biology.
AB  - Much has been written about the need for continuing education and training to
      enable life scientists and computer scientists to manage and exploit the
      different types of biological data now becoming available. Here we describe the
      development of an online programme that combines short training courses, so that
      those who require an educational programme can progress to complete a formal
      qualification. Although this flexible approach fits the needs of course
      participants, it does not fit easily within the organizational structures of a
      campus-based university. 

PMID- 22988256
TI  - A comprehensive evaluation of normalization methods for Illumina high-throughput
      RNA sequencing data analysis.
AB  - During the last 3 years, a number of approaches for the normalization of RNA
      sequencing data have emerged in the literature, differing both in the type of
      bias adjustment and in the statistical strategy adopted. However, as data
      continue to accumulate, there has been no clear consensus on the appropriate
      normalization method to be used or the impact of a chosen method on the
      downstream analysis. In this work, we focus on a comprehensive comparison of
      seven recently proposed normalization methods for the differential analysis of
      RNA-seq data, with an emphasis on the use of varied real and simulated datasets
      involving different species and experimental designs to represent data
      characteristics commonly observed in practice. Based on this comparison study, we
      propose practical recommendations on the appropriate normalization method to be
      used and its impact on the differential analysis of RNA-seq data. 

PMID- 22988257
TI  - On the classification of microarray gene-expression data.
AB  - We consider the classification of microarray gene-expression data. First,
      attention is given to the supervised case, where the tissue samples are
      classified with respect to a number of predefined classes and the intent is to
      assign a new unclassified tissue to one of these classes. The problems of forming
      a classifier and estimating its error rate are addressed in the context of there
      being a relatively small number of observations (tissue samples) compared to the
      number of variables (that is, the genes, which can number in the tens of
      thousands). We then proceed to the unsupervised case and consider the clustering
      of the tissue samples and also the clustering of the gene profiles. Both problems
      can be viewed as being non-standard ones in statistics and we address some of the
      key issues involved. The focus is on the use of mixture models to effect the
      clustering for both problems. 

PMID- 22988258
TI  - What can modelling provide to cardiac physiology?

PMID- 22988259
TI  - Sacrococcygeal teratoma: a literature review.
AB  - OBJECTIVE: To review the current and relevant literature pertaining to the
      origin, imaging, and treatment for the sacrococcygeal teratoma in order to obtain
      information beneficial for radiologic technologists. METHODS: Both peer-reviewed
      articles and contemporary imaging textbooks were used in the research for this
      review. The material was analyzed further for practical and instructive
      components for imaging professionals. RESULTS: The inquiry regarding the origin,
      imaging, and treatment of the sacrococcygeal teratoma yielded important facts and
      clinically useful information that radiologic technologists can use. CONCLUSION:
      Because the sacrococcygeal teratoma is the most common congenital tumor found in
      newborns, all imaging professionals who may be asked to actively or indirectly
      care for a patient diagnosed with the condition should have a fundamental
      knowledge of the origin, imaging, and treatment of this potentially fatal tumor.

PMID- 22988260
TI  - Radiologist views of positron emission mammography.
AB  - BACKGROUND: Early detection and diagnosis of malignant breast lesions are vital
      to survival. Although current imaging modalities such as mammography,
      ultrasonography, and magnetic resonance imaging focus on an anatomic approach,
      they do not provide sufficient data about the pathophysiology of malignant breast
      lesions. Positron emission mammography (PEM) is an innovative technology
      specifically designed to visualize the physiologic and metabolic processes in
      malignant breast lesions, but it remains underused as a diagnostic tool.
      OBJECTIVE: The purpose of this research is to provide quantitative and
      qualitative evidence from radiologists' perspective about the efficacy of
      physiologic imaging and the future implementation of PEM as a diagnostic tool in
      clinical practice. METHODS: Radiologists were asked to complete a survey designed
      to elicit their perspective on the role of physiologic imaging in detecting and
      diagnosing breast cancer and on PEM as an adjunct modality. RESULTS: Based on the
      survey data, 66% of participants considered physiologic imaging to be beneficial
      because it provides additional diagnostic data, and 67% supported the future use
      of PEM as an adjunct to mammography. CONCLUSION: Although preliminary indications
      favor the use of adjunct PEM, further research is needed before it becomes a
      common clinical tool.

PMID- 22988261
TI  - Stopping the chain of infection in the radiology suite.
AB  - Billions of dollars and thousands of lives are lost each year because of
      communicable diseases. The basic component of every communicable disease
      transmission is the chain of infection. By breaking just 1 link in the chain, a
      communicable disease cannot be passed on to another individual. Radiologic
      technologists have the ability to continue the chain of infection or stop
      transmission. This article explores how a disease is transmitted and what
      techniques are available to stop transmission.

PMID- 22988262
TI  - Stress management for the radiologic technologist.
AB  - Changes in technology in the radiology department and an emphasis on multitasking
      can lead to stress and burnout, along with the potential for medical errors. A
      shift in viewpoint and exercises in self-evaluation can help radiologic
      technologists learn to manage change in a positive manner. Learning to approach
      change through a series of transitions and positive steps can reduce stress at
      work and at home.

PMID- 22988263
TI  - Steps to a successful site visit.

PMID- 22988267
TI  - Best practices in digital radiography.

PMID- 22988268
TI  - The difference between peer review and nonpeer review.

PMID- 22988269
TI  - Image gently: using exposure indicators to improve pediatric digital radiography.

PMID- 22988270
TI  - Central venous access using a translumbar hemiazygos approach.

PMID- 22988271
TI  - Linear artifacts caused by grid damage.

PMID- 22988272
TI  - Safety concerns and recommendations.

PMID- 22988273
TI  - Safety concerns and recommendations.

PMID- 22988275
TI  - Safety concerns and recommendations.

PMID- 22988276
TI  - Safety concerns and recommendations.

PMID- 22988279
TI  - Breast cancer: age-related factors.
AB  - The literature on breast cancer inevitably includes age as a risk factor for the
      disease, and there is considerable controversy regarding the best age for women
      to start screening mammography. A woman's breast develops and changes over the
      course of her lifetime, and at various times is more or less susceptible to
      cancer. Developmental differences also affect breast imaging. This article
      focuses on the age groups outside the majority of women who receive breast cancer
      diagnoses, instead emphasizing effects of age on the very youngest and oldest
      women.

PMID- 22988280
TI  - Bayesian analysis of RNA sequencing data by estimating multiple shrinkage priors.
AB  - Next generation sequencing is quickly replacing microarrays as a technique to
      probe different molecular levels of the cell, such as DNA or RNA. The technology
      provides higher resolution, while reducing bias. RNA sequencing results in counts
      of RNA strands. This type of data imposes new statistical challenges. We present
      a novel, generic approach to model and analyze such data. Our approach aims at
      large flexibility of the likelihood (count) model and the regression model alike.
      Hence, a variety of count models is supported, such as the popular NB model,
      which accounts for overdispersion. In addition, complex, non-balanced designs and
      random effects are accommodated. Like some other methods, our method provides
      shrinkage of dispersion-related parameters. However, we extend it by enabling
      joint shrinkage of parameters, including those for which inference is desired. We
      argue that this is essential for Bayesian multiplicity correction. Shrinkage is
      effectuated by empirically estimating priors. We discuss several parametric
      (mixture) and non-parametric priors and develop procedures to estimate
      (parameters of) those. Inference is provided by means of local and Bayesian false
      discovery rates. We illustrate our method on several simulations and two data
      sets, also to compare it with other methods. Model- and data-based simulations
      show substantial improvements in the sensitivity at the given specificity. The
      data motivate the use of the ZI-NB as a powerful alternative to the NB, which
      results in higher detection rates for low-count data. Finally, compared with
      other methods, the results on small sample subsets are more reproducible when
      validated on their large sample complements, illustrating the importance of the
      type of shrinkage.

PMID- 22988281
TI  - Incorporating group correlations in genome-wide association studies using
      smoothed group Lasso.
AB  - In genome-wide association studies, penalization is an important approach for
      identifying genetic markers associated with disease. Motivated by the fact that
      there exists natural grouping structure in single nucleotide polymorphisms and,
      more importantly, such groups are correlated, we propose a new penalization
      method for group variable selection which can properly accommodate the
      correlation between adjacent groups. This method is based on a combination of the
      group Lasso penalty and a quadratic penalty on the difference of regression
      coefficients of adjacent groups. The new method is referred to as smoothed group
      Lasso (SGL). It encourages group sparsity and smoothes regression coefficients
      for adjacent groups. Canonical correlations are applied to the weights between
      groups in the quadratic difference penalty. We first derive a GCD algorithm for
      computing the solution path with linear regression model. The SGL method is
      further extended to logistic regression for binary response. With the assistance
      of the majorize-minimization algorithm, the SGL penalized logistic regression
      turns out to be an iteratively penalized least-square problem. We also suggest
      conducting principal component analysis to reduce the dimensionality within
      groups. Simulation studies are used to evaluate the finite sample performance.
      Comparison with group Lasso shows that SGL is more effective in selecting true
      positives. Two datasets are analyzed using the SGL method.

PMID- 22988282
TI  - A modified Phase I trial of radiation dose escalation in 3D conformal radiation
      therapy with concurrent vinorelbine and carboplatin chemotherapy for non-small
      cell lung cancer.
AB  - The Radiation Therapy Oncology Group reported a maximum tolerated dose of 74 Gy
      for patients with non-small cell lung cancer (NSCLC); however, it was unclear
      whether this dose could be safely administered to Asian patients due to
      differences in their physique compared to Western patients. We therefore
      conducted a modified Phase I trial to determine whether 70 Gy could be safely
      delivered to Chinese patients with NSCLC undergoing 3D-conformal radiation
      therapy (3D-CRT) with concurrent chemotherapy. Previously untreated NSCLC
      patients received 3D-CRT (2 Gy/day, 5 fractions per week). Three dose levels were
      examined: 62, 66 and 70 Gy. Two cycles of concurrent chemotherapy (vinorelbine
      and carboplatin) were started on the first day of radiation therapy. Dose
      limiting toxicity (DLT) was defined as severe or life-threatening side effects
      that altered the continued implementation of chemoradiotherapy. Among the 19
      patients recruited in this study, most of the haematologic and non-haematologic
      toxicities were mild to moderate and clinically manageable. Only one patient, in
      the 70 Gy cohort, experienced a DLT of Grade 3 radiation-induced pneumonia. The
      overall response rate was 77.8% (14/18). The median progression-free survival
      (PFS) was 12 months, and the 1-year PFS was 37.6%. Our results support both the
      feasibility of incorporating 3D-CRT with concurrent vinorelbine and carboplatin
      and a dose escalation to 70 Gy for Chinese patients with NSCLC, based on the
      acceptable toxicity and encouraging overall response and survival rates. A
      further evaluation of this regimen in a prospective Phase II trial is ongoing.

PMID- 22988283
TI  - Radiotherapy for stage I or II hypopharyngeal carcinoma.
AB  - Hypopharyngeal squamous cell carcinoma (HPSCC) is usually diagnosed at an
      advanced stage, and early-stage HPSCC is relatively rare. Because of the rarity
      of early-stage HPSCC, few reports have been published on the efficacy of
      radiotherapy (RT) in its treatment. We retrospectively reviewed the clinical
      records of 45 consecutive patients with Stage I and II HPSCC from May 1991 to
      June 2010. Patient characteristics were as follows: median age, 66 years (range,
      44-90 years); male/female, 39/6; and T1/T2, 27/18. The irradiation dose ranged
      from 60 to 72 Gy (median: 70 Gy). Of the 45 patients, 21 underwent concurrent
      chemotherapy. With a median follow-up period of 62 months, the 5-year overall
      survival rate was 81%. Local failure occurred in 5 patients, and the 5-year local
      control rate was 83%. All local recurrences were successfully salvaged by
      surgery. The 5-year functional larynx preservation rate was 92%. Acute toxicity
      was manageable. Grade 3 laryngeal edema and Grade 3 hypothyroidism occurred in 1
      patient each. No other late adverse events of Grade 3 or greater were observed.
      Based on these results, RT seemed to be an effective treatment modality for early
      HPSCC, with favorable organ preservation and acceptable adverse events. Early
      detection and accurate management of local recurrence and second malignancy was
      deemed to be critical.

PMID- 22988284
TI  - Analysis of late toxicity associated with external beam radiation therapy for
      prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions:
      a survey study by the Osaka Urological Tumor Radiotherapy Study Group.
AB  - We aimed to analyse late toxicity associated with external beam radiation therapy
      (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement,
      with the focus on the effect of 3D (CT) simulation and portal field size. We
      collected data concerning patients with localized prostate adenocarcinoma who had
      been treated with EBRT at five institutions in Osaka, Japan, between 1998 and
      2006. All had been treated with 70 Gy in 35 fractions, using the classical 4
      field technique with gantry angles of 0 degrees , 90 degrees , 180 degrees  and
      270 degrees . Late toxicity was evaluated strictly in terms of the Common
      Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were
      analysed, with a median follow-up of 4.5 years (range 1.0-11.6). The 5-year
      overall and cause-specific survival rates were 93% and 96%, respectively. The
      mean +/- SD portal field size in the right-left, superior-inferior, and anterior
      posterior directions was, respectively, 10.8 +/- 1.1, 10.2 +/- 1.0 and 8.8 +/-
      0.9 cm for 2D simulation, and 8.4 +/- 1.2, 8.2 +/- 1.0 and 7.7 +/- 1.0 cm for 3D
      simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial
      5-year Grade 2-3 genitourinary and gastrointestinal (GI) late toxicity rates were
      6% and 14%, respectively, while the corresponding late rectal bleeding rate was
      23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform
      setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the
      resultant reduction in portal field size were significantly associated with
      reduced late GI toxicity, especially with less rectal bleeding.

PMID- 22988285
TI  - Exemplar variability facilitates rapid learning of an otherwise unlearnable
      grammar by individuals with language-based learning disability.
AB  - PURPOSE: Even without explicit instruction, learners are able to extract
      information about the form of a language simply by attending to input that
      reflects the underlying grammar. In this study, the authors explored the role of
      variability in this learning by asking whether varying the number of unique
      exemplars heard by the learner affects learning of an artificial syntactic form.
      METHOD: Learners with normal language (n = 16) and language-based learning
      disability (LLD; n = 16) were exposed to strings of nonwords that represented an
      underlying grammar. Half of the learners heard 3 exemplars 16 times each (low
      variability group), and the other half of the learners heard 24 exemplars twice
      each (high variability group). Learners were then tested for recognition of items
      heard and generalization of the grammar with new nonword strings. RESULTS: Only
      those learners with LLD who were in the high variability group were able to
      demonstrate generalization of the underlying grammar. For learners with normal
      language, both those in the high and the low variability groups showed
      generalization of the grammar, but relative effect sizes suggested a larger
      learning effect in the high variability group. CONCLUSION: The results
      demonstrate that the structure of the learning context can determine the ability
      to generalize from specific training items to novel cases.

PMID- 22988286
TI  - Sentence comprehension in specific language impairment: a task designed to
      distinguish between cognitive capacity and syntactic complexity.
AB  - PURPOSE: This study examined sentence comprehension in children with specific
      language impairment (SLI) in a manner designed to separate the contribution of
      cognitive capacity from the effects of syntactic structure. METHOD: Nineteen
      children with SLI, 19 typically developing children matched for age (TD-A), and
      19 younger typically developing children (TD-Y) matched according to sentence
      comprehension test scores responded to sentence comprehension items that varied
      in either length or their demands on cognitive capacity, based on the nature of
      the foils competing with the target picture. RESULTS: The TD-A children were
      accurate across all item types. The SLI and TD-Y groups were less accurate than
      the TD-A group on items with greater length and, especially, on items with the
      greatest demands on cognitive capacity. The types of errors were consistent with
      failure to retain details of the sentence apart from syntactic structure.
      CONCLUSIONS: The difficulty in the more demanding conditions seemed attributable
      to interference. Specifically, the children with SLI and the TD-Y children
      appeared to have difficulty retaining details of the target sentence when the
      information reflected in the foils closely resembled the information in the
      target sentence.

PMID- 22988288
TI  - Referential communication in children with ADHD: challenges in the role of a
      listener.
AB  - PURPOSE: Successful communication requires that listeners accurately interpret
      the meaning of speakers' statements. The present work examined whether children
      with and without attention-deficit/hyperactivity disorder (ADHD) differ in their
      ability to interpret referential statements (i.e., phrases that denote objects or
      events) from speakers. METHOD: Children (6 to 9 years old), diagnosed with ADHD
      (n = 27) and typically developing (n = 26), took part in an interactive task in
      which they were asked by an adult speaker to retrieve objects from a display
      case. Children interpreted the referential statements in contexts that either did
      or did not require perspective-taking. Children's eye movements and object
      choices were recorded. Parents completed questionnaires assessing their child's
      frequency of ADHD symptoms and pragmatic communicative abilities. RESULTS:
      Behavioral and eye movement measures revealed that children with ADHD made more
      interpretive errors and were less likely to consider target referents across the
      2 communicative conditions. Furthermore, ADHD symptoms related to children's
      performance on the communicative task and to parental report of the child's
      pragmatic skills. CONCLUSION: Children with ADHD are less accurate in their
      interpretations of referential statements. Such difficulties would lead to
      greater occurrences of miscommunication.

PMID- 22988287
TI  - Rapid naming by children with and without specific language impairment.
AB  - PURPOSE: Previous studies have reported that children with specific language
      impairment (SLI) name pictures more slowly than do chronological age-matched
      (CAM) peers. Rapid naming depends on 2 factors known to be problematic for
      children with SLI-lexical retrieval and nonlinguistic speed of processing.
      Although all studies implicate a speed-of-processing deficit as a contributing
      factor, researchers do not agree on the influence of language factors. The
      purpose of the current study was to explore word frequency (WF) and phonotactic
      pattern frequency (PPF) as potential lexical factors contributing to the naming
      deficits experienced by children with SLI. METHOD: Three groups of children-20
      children with SLI (Mage = 9;8 [years;months]), 20 younger vocabulary-matched (VM)
      controls, and 20 CAM controls-named pictures whose labels varied by WF and PPF.
      RESULTS: Reaction time results revealed significant main effects of group (CAM <
      SLI = VM) and WF (high WF < low WF). Effects due to WF were comparable for all
      groups, but a significant Group * PPF interaction revealed that PPF effects were
      greater for children with SLI than for VM or CAM children. CONCLUSION: Results
      replicate previous findings of a naming deficit in children with SLI.
      Furthermore, results suggest that children with SLI are more vulnerable to
      increased competition from words with frequent phonotactic patterns, which also
      come from dense phonological neighborhoods.

PMID- 22988289
TI  - A role of protein degradation in memory consolidation after initial learning and
      extinction learning in the honeybee (Apis mellifera).
AB  - Protein degradation is known to affect memory formation after extinction
      learning. We demonstrate here that an inhibitor of protein degradation, MG132,
      interferes with memory formation after extinction learning in a classical
      appetitive conditioning paradigm. In addition, we find an enhancement of memory
      formation when the same inhibitor is applied after initial learning. This result
      supports the idea that MG132 targets an ongoing consolidation process.
      Furthermore, we demonstrate that the sensitivity of memory formation after
      initial learning and extinction learning to MG132 depends in the same way on the
      number of CS-US trials and the intertrial interval applied during initial
      learning. This supports the idea that the learning parameters during acquisition
      are critical for memory formation after extinction and that protein degradation
      in both learning processes might be functionally linked.

PMID- 22988290
TI  - The GABAergic anterior paired lateral neurons facilitate olfactory reversal
      learning in Drosophila.
AB  - Reversal learning has been widely used to probe the implementation of cognitive
      flexibility in the brain. Previous studies in monkeys identified an essential
      role of the orbitofrontal cortex (OFC) in reversal learning. However, the
      underlying circuits and molecular mechanisms are poorly understood. Here, we use
      the T-maze to investigate the neural mechanism of olfactory reversal learning in
      Drosophila. By adding a reversal training cycle to the classical learning
      protocol, we show that wild-type flies are able to reverse their choice according
      to the alteration of conditioned stimulus (CS)-unconditioned stimulus (US)
      contingency. The reversal protocol induced a specific suppression of the initial
      memory, an effect distinct from memory decay or extinction. GABA down-regulation
      in the anterior paired lateral (APL) neurons, which innervate the mushroom bodies
      (MBs), eliminates this suppression effect and impairs normal reversal. These
      findings reveal that inhibitory regulation from the GABAergic APL neurons
      facilitates olfactory reversal learning by suppressing initial memory in
      Drosophila.

PMID- 22988291
TI  - Alcoholics and the law.

PMID- 22988292
TI  - Prognostic value of the ECG.

PMID- 22988293
TI  - Treating opioid addiction.

PMID- 22988294
TI  - Factors distinguishing skilled and less skilled deaf readers: evidence from four
      orthographies.
AB  - This study aims to enhance understanding of the factors underlying variance in
      the reading comprehension skills of prelingually deaf individuals. Participants
      were 213 sixth through tenth graders with prelingual deafness recruited from four
      orthographic backgrounds (Hebrew, Arabic, English, and German) and allocated to
      three distinct reading profiles (levels). A sentence comprehension test
      manipulating the semantic plausibility of sentences and a word processing
      experiment requiring rapid determination of the semantic relationship between two
      real words or between a real word and a pseudohomophonic letter string were used
      to determine the factors distinguishing skilled from less skilled deaf readers.
      Findings point to deficits in structural (syntactic) knowledge and deficient
      knowledge structures, rather than differences in phonological processing skills,
      as making that distinction. Moreover, the acquisition of such knowledge seems to
      be modified by particularities of the read orthography.

PMID- 22988295
TI  - Impact of peer and teacher relations on deaf early adolescents' well-being:
      comparisons before and after a major school transition.
AB  - This study focused on the peer and teacher relationships of deaf children and the
      effects of these relationships on well-being in school during the transition from
      elementary school to junior high school. Differences due to gender and
      educational context were also considered. In Study 1, the predictive effects of
      peer acceptance, popularity, and teacher support on well-being were examined
      cross-sectionally for early adolescents in Grade 6 (N = 759, 87 deaf) and Grade 7
      (N = 840, 104 deaf). Study 2 examined the effects of the same predictors on well
      being in school longitudinally during the transition to secondary school on a
      subsample of participants from Study 1 (n = 105). Well-being in school was stable
      during the transition for mainstreamed hearing children, but not for deaf
      children. In mainstream schools, school well-being increased for deaf boys but
      decreased for deaf girls. In contrast, in special education schools, school well
      being increased for deaf girls but decreased for deaf boys. Peer acceptance,
      popularity, and relationship with the teacher had different effects on well-being
      for deaf early adolescents in mainstream schools compared to the effects on those
      in special education schools. Moderation by gender was also found.

PMID- 22988296
TI  - The breast cancer susceptibility gene product fibroblast growth factor receptor 2
      serves as a scaffold for regulation of NF-kappaB signaling.
AB  - Fibroblast growth factor (FGF) receptor 2 (FGFR2) has been identified in genome
      wide association studies to be associated with increased breast cancer risk;
      however, its mechanism of action remains unclear. Here we show that the two major
      FGFR2 alternatively spliced isoforms, FGFR2-IIIb and FGFR2-IIIc, interact with
      IkappaB kinase beta and its downstream target, NF-kappaB. FGFR2 inhibits nuclear
      RelA/p65 NF-kappaB translocation and activity and reduces expression of dependent
      transcripts, including interleukin-6. These interactions result in diminished
      STAT3 phosphorylation and reduced breast cancer cell growth, motility, and
      invasiveness. FGFR2 also arrests the epithelial cell-to-mesenchymal cell
      transition (EMT), resulting in attenuated neoplastic growth in orthotopic
      xenografts of breast cancer cells. Our studies provide strong evidence for the
      protective effects of FGFR2 on tumor progression. We propose that FGFR2 serves as
      a scaffold for multiple components of the NF-kappaB signaling complex. Through
      these interactions, FGFR2 isoforms can respond to tissue-specific FGF signals to
      modulate epithelial cell-stromal cell communications in cancer progression.

PMID- 22988297
TI  - A phosphatidylinositol 3-kinase-Pax3 axis regulates Brn-2 expression in melanoma.
AB  - Deregulation of transcription arising from mutations in key signaling pathways is
      a hallmark of cancer. In melanoma, the most aggressive and lethal form of skin
      cancer, the Brn-2 transcription factor (POU3F2) regulates proliferation and
      invasiveness and lies downstream from mitogen-activated protein kinase (MAPK) and
      Wnt/beta-catenin, two melanoma-associated signaling pathways. In vivo Brn-2
      represses expression of the microphthalmia-associated transcription factor, MITF,
      to drive cells to a more stem cell-like and invasive phenotype. Given the key
      role of Brn-2 in regulating melanoma biology, understanding the signaling
      pathways that drive Brn-2 expression is an important issue. Here, we show that
      inhibition of phosphatidylinositol 3-kinase (PI3K) signaling reduces invasiveness
      of melanoma cells in culture and strongly inhibits Brn-2 expression. Pax3, a
      transcription factor regulating melanocyte lineage-specific genes, directly binds
      and regulates the Brn-2 promoter, and Pax3 expression is also decreased upon PI3K
      inhibition. Collectively, our results highlight a crucial role for PI3K in
      regulating Brn-2 and Pax3 expression, reveal a mechanism by which PI3K can
      regulate invasiveness, and imply that PI3K signaling is a key determinant of
      melanoma subpopulation diversity. Together with our previous work, the results
      presented here now place Brn-2 downstream of three melanoma-associated signaling
      pathways.

PMID- 22988298
TI  - Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for
      the phosphorylation of the C-terminal domain of RNA polymerase II.
AB  - CrkRS (Cdc2-related kinase, Arg/Ser), or cyclin-dependent kinase 12 (CKD12), is a
      serine/threonine kinase believed to coordinate transcription and RNA splicing.
      While CDK12/CrkRS complexes were known to phosphorylate the C-terminal domain
      (CTD) of RNA polymerase II (RNA Pol II), the cyclin regulating this activity was
      not known. Using immunoprecipitation and mass spectrometry, we identified a 65
      kDa isoform of cyclin K (cyclin K1) in endogenous CDK12/CrkRS protein complexes.
      We show that cyclin K1 complexes isolated from mammalian cells contain
      CDK12/CrkRS but do not contain CDK9, a presumed partner of cyclin K. Analysis of
      extensive RNA-Seq data shows that the 65-kDa cyclin K1 isoform is the
      predominantly expressed form across numerous tissue types. We also demonstrate
      that CDK12/CrkRS is dependent on cyclin K1 for its kinase activity and that small
      interfering RNA (siRNA) knockdown of CDK12/CrkRS or cyclin K1 has similar effects
      on the expression of a luciferase reporter gene. Our data suggest that cyclin K1
      is the primary cyclin partner for CDK12/CrkRS and that cyclin K1 is required to
      activate CDK12/CrkRS to phosphorylate the CTD of RNA Pol II. These properties are
      consistent with a role of CDK12/CrkRS in regulating gene expression through
      phosphorylation of RNA Pol II.

PMID- 22988299
TI  - Reciprocal phosphorylation of yeast glycerol-3-phosphate dehydrogenases in
      adaptation to distinct types of stress.
AB  - Eukaryotic cells have evolved mechanisms for ensuring growth and survival in the
      face of stress caused by a fluctuating environment. Saccharomyces cerevisiae has
      two homologous glycerol-3-phosphate dehydrogenases, Gpd1 and Gpd2, that are
      required to endure various stresses, including hyperosmotic shock and hypoxia.
      These enzymes are only partially redundant, and their unique functions were
      attributed previously to differential transcriptional regulation and
      localization. We find that Gpd1 and Gpd2 are negatively regulated through
      phosphorylation by distinct kinases under reciprocal conditions. Gpd2 is
      phosphorylated by the AMP-activated protein kinase Snf1 to curtail glycerol
      production when nutrients are limiting. Gpd1, in contrast, is a target of TORC2
      dependent kinases Ypk1 and Ypk2. Inactivation of Ypk1 by hyperosmotic shock
      results in dephosphorylation and activation of Gpd1, accelerating recovery
      through increased glycerol production. Gpd1 dephosphorylation acts
      synergistically with its transcriptional upregulation, enabling long-term growth
      at high osmolarity. Phosphorylation of Gpd1 and Gpd2 by distinct kinases thereby
      enables rapid adaptation to specific stress conditions. Introduction of
      phosphorylation motifs targeted by distinct kinases provides a general mechanism
      for functional specialization of duplicated genes during evolution.

PMID- 22988300
TI  - IkappaB kinase 2 regulates TPL-2 activation of extracellular signal-regulated
      kinases 1 and 2 by direct phosphorylation of TPL-2 serine 400.
AB  - Tumor progression locus 2 (TPL-2) functions as a MEK-1/2 kinase, which is
      essential for Toll-like receptor 4 (TLR4) activation of extracellular signal
      regulated kinase 1 and 2 (ERK-1/2) mitogen-activated protein (MAP) kinases in
      lipopolysaccharide (LPS)-stimulated macrophages and for inducing the production
      of the proinflammatory cytokines tumor necrosis factor and interleukin-1beta. In
      unstimulated cells, association of TPL-2 with NF-kappaB1 p105 prevents TPL-2
      phosphorylation of MEK-1/2. LPS stimulation of TPL-2 MEK-1/2 kinase activity
      requires TPL-2 release from p105. This is triggered by IkappaB kinase 2 (IKK-2)
      phosphorylation of the p105 PEST region, which promotes p105 ubiquitination and
      degradation by the proteasome. LPS activation of ERK-1/2 additionally requires
      transphosphorylation of TPL-2 on serine 400 in its C terminus, which controls TPL
      2 signaling to ERK-1/2 independently of p105. However, the identity of the
      protein kinase responsible for TPL-2 serine 400 phosphorylation remained unknown.
      In the present study, we show that TPL-2 serine 400 phosphorylation is mediated
      by IKK2. The IKK complex therefore regulates two of the key regulatory steps
      required for TPL-2 activation of ERK-1/2, underlining the close linkage of ERK
      1/2 MAP kinase activation to upregulation of NF-kappaB-dependent transcription.

PMID- 22988301
TI  - Regulation of GATA factor expression is distinct between erythroid and mast cell
      lineages.
AB  - The zinc finger transcription factors GATA1 and GATA2 participate in mast cell
      development. Although the expression of these factors is regulated in a cell
      lineage-specific and differentiation stage-specific manner, their regulation
      during mast cell development has not been clarified. Here, we show that the GATA2
      mRNA level was significantly increased while GATA1 was maintained at low levels
      during the differentiation of mast cells derived from mouse bone marrow (BMMCs).
      Unlike in erythroid cells, forced expression or small interfering RNA (siRNA)
      mediated knockdown of GATA1 rarely affected GATA2 expression, and vice versa, in
      mast cells, indicating the absence of cross-regulation between Gata1 and Gata2
      genes. Chromatin immunoprecipitation assays revealed that both GATA factors bound
      to most of the conserved GATA sites of Gata1 and Gata2 loci in BMMCs. However,
      the GATA1 hematopoietic enhancer (G1HE) of the Gata1 gene, which is essential for
      GATA1 expression in erythroid and megakaryocytic lineages, was bound only weakly
      by both GATA factors in BMMCs. Furthermore, transgenic-mouse reporter assays
      revealed that the G1HE is not essential for reporter expression in BMMCs and
      peritoneal mast cells. Collectively, these results demonstrate that the
      expression of GATA factors in mast cells is regulated in a manner quite distinct
      from that in erythroid cells.

PMID- 22988302
TI  - Unwalkable neighborhoods, poverty, and the risk of diabetes among recent
      immigrants to Canada compared with long-term residents.
AB  - OBJECTIVE: This study was designed to examine whether residents living in
      neighborhoods that are less conducive to walking or other physical activities are
      more likely to develop diabetes and, if so, whether recent immigrants are
      particularly susceptible to such effects. RESEARCH DESIGN AND METHODS: We
      conducted a population-based, retrospective cohort study to assess the impact of
      neighborhood walkability on diabetes incidence among recent immigrants (n =
      214,882) relative to long-term residents (n = 1,024,380). Adults aged 30-64 years
      who were free of diabetes and living in Toronto, Canada, on 31 March 2005 were
      identified from administrative health databases and followed until 31 March 2010
      for the development of diabetes, using a validated algorithm. Neighborhood
      characteristics, including walkability and income, were derived from the Canadian
      Census and other sources. RESULTS: Neighborhood walkability was a strong
      predictor of diabetes incidence independent of age and area income, particularly
      among recent immigrants (lowest [quintile 1 {Q1}] vs. highest [quintile 5 {Q5}]
      walkability quintile: relative risk [RR] 1.58 [95% CI 1.42-1.75] for men; 1.67
      [1.48-1.88] for women) compared with long-term residents (Q1 to Q5) 1.32 [1.26
      1.38] for men; 1.24 [1.18-1.31] for women). Coexisting poverty accentuated these
      effects; diabetes incidence varied threefold between recent immigrants living in
      low-income/low walkability areas (16.2 per 1,000) and those living in high
      income/high walkability areas (5.1 per 1,000). CONCLUSIONS: Neighborhood
      walkability was inversely associated with the development of diabetes in our
      setting, particularly among recent immigrants living in low-income areas.

PMID- 22988303
TI  - Neural stem cells: therapeutic potential for neurodegenerative diseases.
AB  - INTRODUCTION: Neural stem cells (NSCs) from specific brain areas or developed
      from progenitors of different sources are of therapeutic potential for
      neurodegenerative diseases. SOURCES OF DATA: Treatment strategies involve the (i)
      transplantation of exogenous NSCs; (ii) pharmacological modulations of endogenous
      NSCs and (iii) modulation of endogenous NSCs via the transplantation of exogenous
      NSCs. AREAS OF AGREEMENT: There is a consensus about the therapeutic potential of
      transplanted NSCs. The ability of NSCs to home into areas of central nervous
      system injury allows their delivery by intravenous injection. There is also a
      general agreement about the neuroprotective mechanisms of NSCs involving a
      'bystander effect'. AREAS OF CONTROVERSY: Individual laboratories may be using
      phenotypically diverse NSCs, since these cells have been differentiated by a
      variety of neurotrophins and/or cultured on different ECM proteins, therefore
      differing in the expression of neuronal markers. GROWING POINTS: Optimization of
      the dose, delivery route, timing of administration of NSCs, their interactions
      with the immune system and combination therapies in conjunction with tissue
      engineered neural prostheses are under investigation. AREAS TIMELY FOR DEVELOPING
      RESEARCH: In-depth understanding of the biological properties of NSCs, including
      mechanisms of therapy, safety, efficacy and elimination from the organism. These
      areas are central for further use in cell therapy. CAUTIONARY NOTE: As long as
      critical safety and efficacy issues are not resolved, we need to be careful in
      translating NSC therapy from animal models to patients.

PMID- 22988305
TI  - Prison environment and health.

PMID- 22988306
TI  - Optimising the value of interventions for populations.

PMID- 22988304
TI  - Use of population based background rates of disease to assess vaccine safety in
      childhood and mass immunisation in Denmark: nationwide population based cohort
      study.
AB  - OBJECTIVES: To predict the number of selected outcomes temporally associated but
      not caused by vaccination, to aid causality assessment of adverse events arising
      after mass immunisation in a paediatric population. DESIGN: Nationwide population
      based cohort study. SETTING: Denmark. PARTICIPANTS: All liveborn infants
      delivered after 1 January 1980. Study population was followed from date of birth
      until hospital admission for selected outcome diagnoses, death, first emigration,
      age 18 years, or 31 December 2009. The study population was subject to vaccines
      used in standard childhood immunisation in Denmark, with 82-93% vaccine coverage.
      MAIN OUTCOME MEASURES: Incidence of acute infectious and post-infectious
      polyneuritis (Guillain-Barre syndrome), acute transverse myelitis, optic
      polyneuritis, facial nerve palsy, anaphylactic shock, seizure, multiple
      sclerosis, autoimmune thrombocytopenia, type 1 diabetes mellitus, juvenile and
      rheumatoid arthritis, narcolepsy, and death of unknown cause stratified by sex,
      age, and season. We predicted the number of events for a hypothetical vaccine
      cohort of 1,000,000 people for follow-up periods of up to 182 days. RESULTS: The
      study included 2,300,227 liveborn infants, yielding 37,262,404 person years of
      follow-up; median follow-up was 16.8 person years. Incidence of outcome diagnoses
      spanned from 0.32 per 100,000 patient years for autoimmune thrombocytopenia to
      189.82 per 100,000 patient years for seizure. Seasonal differences were most
      pronounced for anaphylactic shock, seizure, and multiple sclerosis. Even for rare
      outcomes, numerous events were predicted in the hypothetical vaccine cohort. We
      predicted that 20 cases of type 1 diabetes mellitus, 19 of juvenile or rheumatoid
      arthritis, eight of facial nerve palsy, and five of multiple sclerosis per
      1,000,000 children would occur within 42 days after vaccination. CONCLUSIONS:
      Incorporating exact background rates of disease based on age, sex, and seasonal
      distribution could strengthen vaccine safety assessment, and provides an evidence
      based focus for discussing the incremental risk of newly introduced vaccines.

PMID- 22988307
TI  - Redesigning the general practice consultation to improve care for patients with
      multimorbidity.

PMID- 22988308
TI  - "World's pharmacy" faces new challenges from Western drug companies.

PMID- 22988309
TI  - Critics condemn proposals to restrict use of social media among health staff.

PMID- 22988310
TI  - French government wastes ?15bn a year on useless drugs, book claims.

PMID- 22988311
TI  - Family of man with Down's syndrome takes legal action over "do not resuscitate"
      order.

PMID- 22988312
TI  - Dentomaxillofacial manifestations of Gaucher's disease: preliminary clinical and
      radiographic findings.
AB  - OBJECTIVES: A wide variety of manifestations is presented in patients with
      Gaucher's disease (GD), including bone, haematology and visceral disturbances.
      This study was conducted to ascertain the main maxillofacial abnormalities by
      means of clinical survey, panoramic and cone beam CT (CBCT); to compare the
      patient's group with an age-sex matched control group; and to correlate clinical
      and radiological data. METHODS: Ten patients previously diagnosed with GD were
      submitted to clinical and radiological surveys (CBCT and panoramic radiographs).
      The examination consisted of anamnesis, extra- and intraoral examinations and
      analyses of each patient's records. Imaging data were collected from the point of
      view of 3 observers, and the results compared with a healthy group (20
      individuals) by means of statistical analysis (Fisher's exact test). RESULTS:
      Gaucher patients had significantly more manifestations than otherwise healthy
      carriers. The most prevalent findings were enlarged marrow spaces, generalized
      osteopenia and effacement of jaw structures (mandibular canal, lamina dura and
      mental foramen). Here we describe a case in which thickening of the maxillary
      sinus mucosa was observed on CBCT rather than opacification of the sinus as seen
      on panoramic radiographs. Pathological fractures, root resorption and delay on
      tooth eruption were not observed. CONCLUSIONS: A poor relationship could be
      observed between clinical and radiological data. Patients showed important bone
      manifestations, which require careful diagnostic and surgical planning whenever
      necessary. Although panoramic radiographs have shown significant differences,
      CBCT is more effective in pointing out differences between patients and a control
      group, thus showing it as an important tool for evaluation of Gaucher patients.

PMID- 22988313
TI  - A false presence of bifid mandibular canals in panoramic radiographs.

PMID- 22988314
TI  - Our time: a call to save preventable death from cardiovascular disease (heart
      disease and stroke).

PMID- 22988315
TI  - Social determinants of sexual health.

PMID- 22988316
TI  - Euthanasia: Evolving role of the psychiatrists in India.

PMID- 22988317
TI  - Psychiatric oncology: Cancer in mind.
AB  - Psychosocial oncology is an upcoming area of interest, which deals with numerous
      psychiatric, psychological, and social aspects of malignancies. Psychiatric
      oncology relates to some of the common psychological and emotional problems
      encountered in persons with malignancy and their formal and informal caregivers.
      This oration will discuss the importance of this field of Consultation Liaison
      Psychiatry, with a focus on the research and practice in the Indian setting. This
      presentation will also share the findings and researches of the presenter. All
      these range from studies on cancer pain and palliative care, screening for
      psychiatric morbidity, quality of life, communication skills for health
      professionals in breaking bad news and handling difficult questions, and
      counseling. The findings on researches on somatization and illness behavior in
      cancer patients would highlight newer challenges in this field. Caregivers of
      persons with cancer are as important as the patient, but usually ignored. The
      stress, strain, burden, positive emotions, and coping in the context of care
      giving for persons with cancer are being increasingly realized. Professional
      caregivers should be aware of caregiver difficulties and support them through
      their ordeal. Lastly, the importance of dealing with staff stress and burnout
      among health professionals looking after families with cancer patients and
      survivors will be emphasized.

PMID- 22988319
TI  - Twenty-five years of schizophrenia: The Madras longitudinal study.
AB  - AIM: To determine the 25 year follow-up of subjects originally enrolled in the
      Study of factors associated with course and outcome of schizophrenia (SOFACOS) at
      Chennai. MATERIALS AND METHODS: All subjects who were followed up were
      administered the same research tools which were done at inclusion, namely the PSE
      & PPHS. RESULTS: At the end of 25 years, 47 of the original ninety subjects were
      assessed completely. Twenty five (26%) had died and 18 (20%) were lost to follow
      up during the 25 year period. 32 of the 47 followed up were in partial or total
      remission. Outcome was good in 27.7%, intermediate in 52% and poor in 19%. More
      men were single and more women were either married or separated. Gender
      differences were not marked. CONCLUSIONS: This is one of the few prospective,
      long term follow up studies from India. Although outcome was good in those
      followed up, the numbers who died and could not be followed up causes concern.

PMID- 22988318
TI  - Position statement and guidelines on unmodified electroconvulsive therapy.
AB  - BACKGROUND: In modern day psychiatric practice, it is assumed as a matter of fact
      that when electroconvulsive therapy (ECT) is administered, it will be
      administered under anesthesia and with succinylcholine (or its equivalent)
      modification. Yet, as surveys indicate, there is considerable practice of
      unmodified ECT in developing countries and, to a small extent, in the developed
      world, as well. MATERIALS AND METHODS: This document examines historical and
      recent literature on the geographical practice, physiology, efficacy, and adverse
      effects of unmodified ECT. Particular attention is paid to musculoskeletal risks.
      RESULTS: Although almost all the research is of poor methodological quality,
      there is a good reason to accept that unmodified ECT is associated with a wide
      range of adverse consequences, important among which are musculoskeletal
      complications, pre-ECT anxiety, and post-ECT confusion. However, it appears from
      recent data that these risks are not as large as historically portrayed. Possibly
      explanations are suggested, with seizure modification using parenteral
      benzodiazepines as a special possibility. CONCLUSIONS: Under exceptional
      circumstances, if ECT is strongly indicated and seizure modification with
      succinylcholine is not feasible, unmodified ECT, especially benzodiazepine
      modified ECT, may be a viable option. A detailed set of recommendations for such
      use of unmodified ECT is proposed along with necessary checks and balances. This
      document has been approved by the Indian Psychatric Society, the Indian
      Association of Biological Psychiatry, and the Indian Association of Private
      Psychiatry (which commissioned the preparation of the document).

PMID- 22988320
TI  - A cross-sectional study of factors associated with adolescent sexual activity.
AB  - CONTEXT: Adolescents constitute about 20% of our population and increasingly more
      of them are initiating sexual activity at an early age. Several behaviors
      associated with adolescence like masturbation, expression of
      masculinity/femininity, lifestyle habits like attending late night parties, and
      consumption of alcohol have been variously implicated in initiating sexual
      activities. Sexual abuse can also lead to premature sexualization. In view of few
      worthwhile studies from India that have dealt with these issues this study was
      undertaken. AIMS: To elicit information from two co-education schools adolescent
      boys and girls on matters related to pubescence, sexual experiences, and sexual
      health. SETTINGS AND DESIGN: Study subjects involved students from class IX to
      XII in two co-education schools. Consent of parents was taken to administer the
      questionnaire to their wards. MATERIALS AND METHODS: A total of 586 out of 1580
      students completed a self-reporting questionnaire on matters related to
      sexuality. Statistical Analysis EpiInfo6 Software was used. RESULTS: Significant
      association was found among those holding the view that having sex proves their
      masculinity, being sexually abused, masturbation among boys, and sexual activity.
      A significantly large number of boys and girls are unaware of role of alcohol on
      sexual activity and that pregnancy can be caused by single intercourse.
      CONCLUSIONS: This was probably the first such comparative study from India.
      Mechanisms need to be evaluated to help adolescents understand their sexual
      attitudes and situations that are likely to provoke sexual activity. Therefore,
      not only more detailed and longitudinal studies are needed to understand these
      relations in a better perspective, but also a well-planned educational program
      for adolescents is a need of the hour.

PMID- 22988321
TI  - Mental health problems among inhabitants of old age homes: A preliminary study.
AB  - BACKGROUND: An exceptional increase in the number and proportion of older adults
      in the country, rapid increase in nuclear families, and contemporary changes in
      psychosocial matrix and values often compel this segment of society to live alone
      or in old age homes. As this group of people is more vulnerable to mental health
      problems, therefore a pilot study was carried out by the Department of Geriatric
      Mental Health, Lucknow with following aim. AIM: To study mental health and
      associated morbidities among inhabitants of old age homes. MATERIALS AND METHODS:
      It was an exploratory study in which information about available old age homes at
      Lucknow were obtained and three of them were randomly selected. All the heads of
      these institutions were contacted and permission to carry out the study was
      obtained. Consent from the participants was obtained. Survey Psychiatric
      Assessment Schedule (SPAS), Mini Mental State Examination (MMSE), Mood Disorder
      Questionnaire (MDQ), and SCAN-based clinical interviews were applied for
      assessment by a trained research staff. RESULTS: Forty five elderly inhabitants
      who had given their consent to participate in the study were interviewed.
      Depression (37.7%) was found to be the most common mental health problem followed
      by anxiety disorders (13.3%) and dementia (11.1%). CONCLUSIONS: A majority of the
      inhabitants (64.4%) were having psychiatric morbidity and no one was observed
      physically fit. Large sample studies are needed to substantiate the observations.

PMID- 22988322
TI  - Study to assess the prevalence, nature and extent of cognitive impairment in
      people living with AIDS.
AB  - BACKGROUND: HIV directly affects the brain and produces varied psychiatric
      manifestations. 10-30% of patients with AIDS were found to have cognitive
      impairment and the virus is isolated in the CSF in 70% of AIDS patients. AIM: The
      present study is aimed at finding out the prevalence, nature, and extent of
      cognitive changes in AIDS patients. MATERIALS AND METHODS: The consecutive sample
      of 33 patients with AIDS attending the ART center of our college were clinically
      interviewed and administered MMSE, BGT, Wechsler Memory Scale, and International
      HIV Dementia Scale. RESULTS: In clinical assessment, only 1/33 (3%) patients
      could be diagnosed as dementia in HIV disease (ICD10-F02.4). This confirms the
      current Indian reports which indicate a lower prevalence of HIV dementia in our
      population. 2/33 (6%) patients were recognized to have mild cognitive disorder
      due to HIV disease (ICD10-F06.7). Asymptomatic cognitive impairment is very
      common in AIDS patients and it was noted in 69% of our study population. In the
      tests, MMSE was positive in only 3 of the 33 patients (9%) and it was not helpful
      to recognize cognitive deficits in our patients. The Wechsler Memory Scale was
      abnormal in 18 of the 33 patients (55%). BGT was abnormal in 48.5% of patients.
      The International HIV Dementia Scale was the most sensitive instrument and 63.6%
      the patients had abnormal scores in this scale. CONCLUSION: Tests which assess
      cognitive and motor speed may be more helpful than clinical psychiatric interview
      to spot the AIDS patients who have cognitive impairment.

PMID- 22988323
TI  - Comparison between the effect of liothyronine and piracetam on personal
      information, orientation and mental control in patients under treatment with ECT.
AB  - OBJECTIVE: The study aimed to compare the effect of liothyronine and piracetam on
      three subscales of the Wechsler memory test on patients under treatment with ECT.
      MATERIALS AND METHODS: In a double blind clinical trial, 60 of 99 patients
      between 20 and 45 years old, under treatment with ECT were studied in three
      groups. Patients in the allocation groups received liothyronine, piracetam, or
      placebo, from the first session of ECT until 1 month after the last session of
      ECT. Personal information, orientation, and mental control were tested in the
      participants at first, fourth, and last session of ECT and 1 month after the last
      session of ECT. Data were analyzed with Repeated measure ANOVA using SPSS 13.
      RESULTS: There wasn't any significant difference among three groups in
      demographic characteristics before the study and number of ECT sessions
      (P=0.684). After intervention, a significant difference in memory scores was seen
      in third and fourth assessment sessions (0.002). Orientation subscales showed a
      significant difference among four assessment sessions (P=0.001). Personal
      information and mental control never decreased in the liothyronine group. There
      was no significant difference among three studied groups in personal information,
      orientation, and mental control (P>0.05). CONCLUSION: Memory changes due to ECT
      may be limited to some parts of memory like orientation. More powerful studies
      for comparison between the effect of liothyronine and placebo are necessary.

PMID- 22988324
TI  - Neurological soft signs in children with attention deficit hyperactivity
      disorder.
AB  - CONTEXT: Attention deficit hyperactivity disorder (ADHD) is a common
      neurodevelopmental disorder with wide repercussions. Since it is etiologically
      related to delayed maturation, neurological soft signs (NSS) could be a tool to
      assess this. Further the correlation of NSS with severity and type of ADHD and
      presence of Specific Learning Disability (SLD) would give further insight into
      it. AIMS: To study neurological soft signs and risk factors (type, mode of
      delivery, and milestones) in children with ADHD and to correlate NSS with type
      and severity of ADHD and with co-morbid Specific Learning Disability. SETTINGS
      AND DESIGN: The study was carried out in Child care services of a tertiary
      teaching urban hospital. It was a cross-sectional single interview study.
      MATERIALS AND METHODS: 52 consecutive children diagnosed as having ADHD were
      assessed for the presence of neurological soft signs using Revised Physical and
      Neurological Examination soft Signs scale (PANESS). The ADHD was rated by parents
      using ADHD parent rating scale. STATISTICAL ANALYSIS: The data was analyzed using
      the chi-squared test and Pearson's co-relational analysis. RESULTS AND
      CONCLUSIONS: Neurological soft signs are present in 84% of children. They are
      equally present in both the inattentive-hyperactive and impulsive-hyperactive
      types of ADHD. The presence of neurological soft signs in ADHD are independent of
      the presence of co-morbid SLD. Dysrrhythmias and overflow with gait were
      typically seen for impulsive-hyperactive type and higher severity of ADHD is
      related to more errors.

PMID- 22988325
TI  - Investigation of the possible role of Shankapushpi in the attenuation of ECT
      induced amnestic deficits.
AB  - INTRODUCTION: Shankapushpi (Evolvulus alsinoides and others) has received mention
      in traditional Indian writings as a potential enhancer of cognitive functioning.
      This study used an animal model to examine whether Shankapushpi improves learning
      and memory and attenuates anterograde and retrograde amnesia associated with
      electroconvulsive shocks (ECS). MATERIALS AND METHODS: Adult, male, Sprague
      Dawley rats (n=64) were treated with an aqueous extract of Shankapushpi or
      vehicle all through the 13-day study. From Days 1 to 8, the animals received
      Shankapushpi or vehicle alone. On Days 8-10, the animals were trained in a T
      maze. On Day 11, they received two true or sham 30 mC ECS 5 h apart. On Day 12,
      recall of pre-ECS training was examined, and on Day 13, new learning was
      assessed. RESULTS: Shankapushpi-treated rats did not show better learning during
      the pre-ECS phase (Days 8-10). Seizure duration was not influenced by
      Shankapushpi treatment (Day 11). Shankapushpi did not attenuate ECS-induced
      retrograde amnesia (Day 12). ECS did not impair new learning, and the effect of
      Shankapushpi herein, therefore, could not be ascertained (Day 13). CONCLUSIONS:
      In this animal model of learning and memory, and of ECS-induced retrograde
      amnesia, Shankapushpi was found to have no favorable or unfavorable effects on
      either cognitive or seizure duration parameters. These findings diminish
      expectations of cognitive and anticonvulsant benefits of simple Shankapushpi
      decoctions in clinical settings, but do not preclude benefits with extracts
      obtained and concentrated by using other methods.

PMID- 22988327
TI  - Euthanasia: An Indian perspective.
AB  - In our society, the palliative care and quality of life issues in patients with
      terminal illnesses like advanced cancer and AIDS have become an important concern
      for clinicians. Parallel to this concern has arisen another controversial issue
      euthanasia or "mercy -killing" of terminally ill patients. Proponents of
      physician-assisted suicide (PAS) feel that an individual's right to autonomy
      automatically entitles him to choose a painless death. The opponents feel that a
      physician's role in the death of an individual violates the central tenet of the
      medical profession. Moreover, undiagnosed depression and possibility of social
      'coercion' in people asking for euthanasia put a further question mark on the
      ethical principles underlying such an act. These concerns have led to strict
      guidelines for implementing PAS. Assessment of the mental state of the person
      consenting to PAS becomes mandatory and here, the role of the psychiatrist
      becomes pivotal. Although considered illegal in our country, PAS has several
      advocates in the form of voluntary organizations like "death with dignity"
      foundation. This has got a fillip in the recent Honourable Supreme Court Judgment
      in the Aruna Shaunbag case. What remains to be seen is how long it takes before
      this sensitive issue rattles the Indian legislature.

PMID- 22988328
TI  - Psychiatric assessment and the art and science of clinical medicine.
AB  - The decline of phenomenology was associated with the corresponding rise of
      operational criteria for psychiatric diagnosis. Detailed and nuanced evaluations
      were replaced by symptom checklists, the diversity of clinical phenomena reduced
      to a few "typical symptom" and contexts ignored in favor of symptom criteria.
      This article highlights some issues related to the art and the science of
      clinical examination. It includes conceptual models, matching patients with
      typical typologies, cross-sectional and longitudinal perspectives, symptom
      checklists and contexts, population characteristics, prevalence and predictive
      values, demarcation of abnormalities, and the Bayesian approach to diagnosis. The
      challenge is to rekindle the interest in phenomenology, appreciate the complexity
      of the task of psychiatric assessment and to teach the principles of clinical
      examination.

PMID- 22988326
TI  - Suicide prevention is possible: A perception after suicide attempt.
AB  - BACKGROUND: Suicide is a preventable cause of death, inspite of which its
      incidence is increasing worldwide. Very few studies are done to know the
      perception of suicide attempters regarding prevention of their suicide attempt.
      Such information may be helpful in implementing preventive strategies. This study
      was done to find out whether those who attempted suicide and recovered perceived
      that their suicide attempt could have been prevented or not. MATERIALS AND
      METHODS: Fifty consecutive subjects were recruited by purposive sampling method.
      These subjects were admitted for suicide attempt and were stable after medical
      management. Subjects were assessed using socio-demographic and clinical proforma,
      Pierce suicide intent scale and structured questionnaire to assess their
      perception regarding suicide. Group differences for categorical variables were
      examined with the chi-square test, whereas an independent 't' test was used for
      continuous variables. RESULTS: Analysis revealed that 80% of suicide attempters
      felt that their suicide attempt could have been prevented. 64% of the study
      subjects perceived that family members and near and dear ones could have helped
      in preventing their attempt while 16% of the study subjects perceived that
      society could have helped. CONCLUSIONS: Majority of subjects on recovery from the
      suicide attempt perceived that their suicide attempt could have been prevented by
      family members, near and dear ones and society.

PMID- 22988329
TI  - Poet Bharathi, touched with fire.
AB  - Substance use among creative artists is very common. In this paper, such use by
      the great Tamil poet, Subramani Bharathi, is considered.

PMID- 22988330
TI  - A case of Todd's Palsy following unilateral electroconvulsive therapy.
AB  - This case describes a woman undergoing unilateral electroconvulsive therapy (ECT)
      who developed a Todd's Palsy following the treatment, and which resolved when
      converted to bilateral ECT. We go on to hypothesize that this rare side effect
      may be an indication of the need to switch laterality during a course of ECT.

PMID- 22988331
TI  - Antidepressant-induced mania in obsessive compulsive disorder.
AB  - Serotonin-reuptake inhibitors have come forth to become the mainstay of treatment
      in obsessive compulsive disorder (OCD), predominantly as a result of evidence
      from clinical psychopharmacological response studies. Comorbid psychiatric
      disorders frequent OCD patients, most often depression. Although selective
      serotonin reuptake inhibitors are effective in the treatment of both OCD and
      depressive disorder, all antidepressants are associated with treatment-emergent
      affective switch. We present a 48-year-old patient with OCD, on antidepressants,
      initially for OCD and later for depression as well. She switched to mania after
      20 years of treatment, which responded to olanzapine and divalproex sodium.

PMID- 22988332
TI  - Trichotillomania with trichorhizophagia in a schizophrenic patient: Case report
      and review of literature.
AB  - Trichotillomania is a disorder characterized by chronic hair pulling that often
      results in alopecia. Eating the part of hair pulled out is a common practice and
      trichorhizophagia is a new term to denote the habit of eating the root of hairs
      pulled out, associated with trichotillomania. Many psychiatric disorders are
      prevalent among patients with trichotillomania. Here we report a case of
      trichotillomania with trichorhizophagia in a 58-year-old man with schizophrenia.
      The various treatment options are also discussed.

PMID- 22988333
TI  - Dissociative stupor, mutism and amnesia in a young man.

PMID- 22988334
TI  - NIMHANS' objective structured clinical assessment and feedback model could be a
      boon for budding medical colleges in India.

PMID- 22988335
TI  - On the Nature of Tintinnid Loricae (Ciliophora: Spirotricha: Tintinnina): a
      Histochemical, Enzymatic, EDX, and High-resolution TEM Study.
AB  - Tintinnids (Ciliophora: Spirotricha: Tintinnina) are occasionally the dominant
      ciliates in the marine plankton. The tintinnid loricae are minute artworks
      fascinating scientists for more than 230 years, but their chemical composition
      remained unclear, viz., chitinous or proteinaceous substances were discussed.
      Since sedimenting loricae contribute to the flux of elements and organic
      compounds in the oceans, knowledge about their nature is necessary in assessing
      their ecological role. Previous techniques and new methods, e.g. enzymatic
      digestion and high-resolution transmission electron microscopy, are applied in
      the present study. A chitinous nature of the loricae is rejected by the Van
      Wisselingh test and failure of chitinase digestion. Only proteins might show a
      resistance against strong hot bases (KOH at 160 degrees C for ~ 40 min. in
      tintinnid loricae) similar to that of chitin. Actually, the presence of nitrogen
      in the EDX analyses and the digestion of at least some loricae by proteinase K
      strongly indicate a proteinaceous nature. Furthermore, the crystal lattice
      revealed by high-resolution TEM in Eutintinnus loricae is similar to the
      proteinaceous surface layer (S-layer) of archaea, and the striation recognizable
      in transverse sections of Eutintinnus loricae has a periodicity resembling that
      of the crystalline proteins in the extruded trichocysts of Paramecium and
      Frontonia. The proteolytic resistance of some loricae does not reject the idea of
      a proteinaceous nature, as proteins in S-layers of some archaea and in most
      naturally occurring prions show comparable reactions. The data from the present
      study and the literature indicate proteins in the loricae of thirteen genera.
      Differences in the proteolytic resistance and staining properties between genera
      and congeners are probably due to deviations in the protein composition and the
      additional substances, e.g. lipids, carbohydrates. At the present state of
      knowledge, correlations between lorica structure, wall texture, ultrastructure of
      the lorica forming granules, and the histochemical and enzymatic findings are not
      evident. Therefore, further studies are required to estimate the taxonomic
      significance of these features and the ecological role of sedimenting loricae.

PMID- 22988336
TI  - Beyond ROC curvature: Strength effects and response time data support continuous
      evidence models of recognition memory.
AB  - A classic question in the recognition memory literature is whether retrieval is
      best described as a continuous-evidence process consistent with signal detection
      theory (SDT), or a threshold process consistent with many multinomial processing
      tree (MPT) models. Because receiver operating characteristics (ROCs) based on
      confidence ratings are typically curved as predicted by SDT, this model has been
      preferred in many studies of recognition memory (Wixted, 2007). Recently, Broder
      and Schutz (2009) argued that curvature in ratings ROCs may be produced by
      variability in scale usage; therefore, ratings ROCs are not diagnostic in
      deciding between the two approaches. From this standpoint, only ROCs constructed
      via experimental manipulations of response bias ('binary' ROCs) are predicted to
      be linear by threshold MPT models. The authors claimed that binary ROCs are
      linear, consistent with the assumptions of threshold MPT models. We compared SDT
      and the double high-threshold MPT model using binary ROCs differing in target
      strength. Results showed that the SDT model provided a superior account of both
      the ROC curvature and the effect of strength compared to the MPT model. Moreover,
      the bias manipulation produced differences in RT distributions that were well
      described by the diffusion model (Ratcliff, 1978), a dynamic version of SDT.

PMID- 22988338
TI  - Tracheal Morphologic and Protein Alterations FollowingShort-Term Cigarette
      Mainstream Smoke Exposure to Rats.
AB  - A short-term 5-day nose-only cigarette smoke exposure study was conducted in
      Fisher 344 rats to identify smoke-induced tracheal protein changes. Groups of 10
      male and female 5 week old rats were assigned to 1 of 4 exposure groups. Animals
      received filtered air, or 75, 200 or 400 mg total particulate matter (TPM)/m(3)
      of diluted 3R4F Kentucky reference cigarette mainstream smoke. Exposures were
      conducted for 3 hrs/day, for 5 consecutive days. Tracheas from half the rats were
      processed for pathology, and tracheas from the other half of the rats frozen
      immediately for proteomics. We hypothesized that smoke will activate tracheal
      inflammatory, apoptotic, proliferative, and stress-induced pathways. Mucosal
      epithelial toxicity from the inhaled material was evidenced by cilia shortening
      and loss of tracheal mucosal epithelium in smoke-exposed animals. Mucosal
      thinning occurred in all smoke-exposed groups with hyperplastic reparative
      responses in the 200 and 400 mg TPM/m(3) groups. Tracheal lysates from control
      vs. treated animals were screened for 800 proteins using antibody-based
      microarray technology and subsequently the most changed proteins evaluated by
      Western blot. Tracheal proteins expressed at high levels that were markedly
      increased or decreased by smoke exposure depended on dose and gender and included
      caspase 5, ERK 1/2 and p38. Signaling pathways common between the morphologic and
      protein changes were stress, apoptosis, cell cycle control, cell proliferation
      and survival. Changes in identified proteins affected by smoke exposure were
      associated with tracheal mucosal pathology, may induce functional tracheal
      changes, and could serve as early indicators of tracheal damage and associated
      disease.

PMID- 22988337
TI  - Comparative histomorphological review of rat and human hepatocellular
      proliferative lesions.
AB  - In this comparative review, histomorphological features of common nonneoplastic
      and neoplastic hepatocyte lesions of rats and humans are examined using H&E
      stained slides. The morphological similarities and differences of both neoplastic
      (hepatocellular carcinoma and hepatocellular adenoma) and presumptive
      preneoplastic lesions (large and small cell change in humans and foci of cellular
      alteration in rats) are presented and discussed. There are major similarities in
      the diagnostic features, growth patterns and behavior of both rat and human
      hepatocellular proliferative lesions and in the process of hepatocarcinogenesis.
      Further study of presumptive preneoplastic lesions in humans and rats should help
      to further define their role in progression to hepatocellular neoplasia in both
      species.

PMID- 22988339
TI  - Lack of Hepatocarcinogenicity of Combinations of Low Doses of 2-amino-3, 8
      dimethylimidazo[4,5- f ]quinoxaline and Diethylnitrosamine in Rats: Indication
      for the Existence of a Threshold for Genotoxic Carcinogens.
AB  - The purposes of the present study were to evaluate the hepatocarcinogenicity of
      concurrent treatment of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and
      diethylnitrosamine (DEN) in rats and to determine whether no effect levels of
      combinations of these two different structural categories of genotoxic
      hepatocarcinogens exist. Two 16-week rat hepatocarcinogenesis assays were
      performed using a total of 790 male F344 rats. In experiment 1, we evaluated the
      effects of concurrent treatment of a subcarcinogenic dose of DEN on rat
      hepatocarcinogenesis induced by various doses of MeIQx. In experiment 2, we
      determined hepatocarcinogenicities of combinations of MeIQx and DEN at
      subcarcinogenic doses, low carcinogenic doses and high carcinogenic doses.
      Quantitative analyses of glutathione S-transferase placental form (GST-P)
      positive foci, a preneoplastic lesion of the liver in rats, revealed that
      concurrent treatment with subcarcinogenic doses of DEN did not enhance MeIQx
      induced rat hepatocarcinogenicity. We also found that concurrent treatment with
      combinations of subcarcinogenic doses of DEN and MeIQx was not
      hepatocarcinogenic, indicating that the combined effects of subcarcinogenic doses
      of DEN and MeIQx were neither additive nor synergistic. Moreover, concurrent
      treatment with low carcinogenic doses of these 2 carcinogens did not show
      additive or synergistic effects. Synergetic effects were observed only in rats
      coadministered high carcinogenic doses of the 2 carcinogens. These results
      demonstrate the existence of no effect levels of combinations of these 2
      genotoxic hepatocarcinogens, and provide new evidence supporting our idea that
      there is a threshold, at least a practical threshold, that should be considered
      when evaluating the risk of genotoxic carcinogens. ( ; : -).

PMID- 22988340
TI  - Histopathological changes in the pancreas from a spontaneous hyperglycemic
      cynomolgus monkey.
AB  - Morphological and immunohistochemical examinations were carried out on the
      pancreas of a hyperglycemic 5-year-old male cynomolgus monkey. Body weight
      gradually decreased from 6 months before termination, accompanying a slight
      reduction in food consumption and anorexia for the last 2 days. The blood glucose
      level was markedly elevated when examined at termination. Histopathologically, in
      the exocrine pancreas, diffuse hyperplasia of centroacinar and intercalated duct
      cells and diffuse atrophy of acinar cells with sporadic apoptosis were observed,
      although most centroacinar and intercalated duct cells were proliferating cell
      nuclear antigen (PCNA)-positive in both the present case and age-matched control
      animals. In the endocrine pancreas, the islets tended to be hypertrophic, with an
      increase in insulin-positive cells in comparison with the age-matched control
      animals. PCNA-positive cells also tended to increase in the islets, although
      positive cells for phospho-histone H3, a marker for mitotic cells, were not
      detected in the endocrine and exocrine pancreas. Moreover, neither inflammation
      nor amyloidosis was noted in the islets. In conclusion, the present case probably
      suffered from early-stage type 2 diabetes mellitus, and it provides fundamental
      information concerning pancreatic histopathology under insulin-related
      derangement in monkeys.

PMID- 22988341
TI  - Spontaneous Mammary Adenocarcinoma in a Twelve-week-old Female Sprague-Dawley
      Rat.
AB  - Spontaneous mammary adenocarcinoma was observed in a 12-week-old female SD rat. A
      movable mass in the right cervical region was found at 11 weeks of age, and the
      rat was sacrificed the following week. The mass was located in the vicinity of
      the right salivary gland and measured 38 mm * 26 mm * 16 mm in gross size. It was
      a firm whitish mass, with a cut surface that was also whitish in appearance.
      Histopathologically, neoplastic cells formed glandular structures that contained
      secreted eosinophilic material. Ultrastructurally, similar secreted material and
      lipid droplets were in the cytoplasm of the neoplastic cells.
      Immunohistochemically, the neoplastic cells were positive for cytokeratin 8,
      cytokeratin 18 and estrogen receptor alpha. Based on these findings, the tumor
      was diagnosed as a mammary gland adenocarcinoma, and we therefore conclude that
      this tumor type can occur spontaneously in female SD rats as young as 12 weeks of
      age.

PMID- 22988342
TI  - Enhancement of Drug Resistance by Lysophosphatidic Acid Receptor-3 in Mouse
      Mammary Tumor FM3A Cells.
AB  - Lysophosphatidic acid (LPA) acts as a simple phospholipid that interacts with G
      protein-coupled transmembrane LPA receptors. Recently, it has been reported that
      each LPA receptor plays different biological roles in acquisition of the
      malignant property of tumor cells. In this study, to assess the involvement of
      LPA receptor-3 (LPA(3)) in cell survival after treatment with anticancer drugs,
      we generated Lpar3-expressing FM3A-a3A9 cells from mouse mammary tumor FM3A cells
      and examined the cell survival rate after treatment with anticancer drugs
      compared with Lpar3-unexpressing cells. Cells were treated with 0.005 to 10 MUM
      of cisplatin (CDDP) or doxorubicin (DOX) for 3 days. For the CDDP and DOX
      treatments, the cell survival rate of FM3A-a3A9 cells was significantly higher
      than that of Lpar3-unexpressing cells. The expression level of the Mdr1a gene in
      FM3A-a3A9 cells was higher than that of Lpar3-unexpressing cells, whereas no
      significant difference in multidrug resistance 1b (Mdr1b) and glutathione S
      transferase mu1 (Gstm1) expressions was found. These results suggest that LPA(3)
      may enhance the cell survival rate after treatment with anticancer drugs in mouse
      mammary tumor cells, correlating with increased expression of the Mdr1 gene.

PMID- 22988343
TI  - Spontaneous gingivitis related to hair penetration in rats.
AB  - Maxillary gingivae from male and female Crl:CD(SD) rats at 12, 16, 21, and 34
      weeks of age were examined histologically. The incidence of gingivitis was
      approximately 40%, with no age or sex predilection, and was most frequent between
      the first and second molar. Lesions were characterized by acute focal
      neutrophilic infiltration into the gingival mucosa, occasionally with
      inflammatory exudate. In severe cases, inflammation extended to the periodontal
      ligament with abscess formation, and adjacent alveolar bone
      destruction/resorption. The most characteristic finding was the presence of hair
      shafts associated with the lesion, which was observed in approximately 80% of the
      rats with gingivitis. These findings suggest that molar gingivitis occurs in rats
      from an early age and persists thereafter, and that the main cause of gingivitis
      in rats is hair penetration into the gingiva. It would be prudent to keep these
      background lesions in mind as potential modifiers in toxicity studies.

PMID- 22988344
TI  - Intravitreal devices for the treatment of vitreous inflammation.
AB  - The eye is a well-suited organ for local delivery of therapeutics to treat
      vitreous inflammation as well as other pathologic conditions that induce visual
      loss. Several conditions are particularly challenging to treat and often require
      chronic courses of therapy. The use of implantable intravitreal devices for drug
      delivery is an emerging field in the treatment of vitreous inflammation as well
      as other ophthalmologic diseases. There are unique challenges in the design of
      these devices which include implants, polymers, and micro- and nanoparticles.
      This paper reviews current and investigational drug delivery systems for treating
      vitreous inflammation as well as other pathologic conditions that induce visual
      loss. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene
      vinyl acetate polymers and polysulfone capillary fibers, and biodegradable
      devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic
      acid, polycaprolactones, and polyanhydrides are reviewed. Clinically used
      implantable devices for therapeutic agents including ganciclovir, fluocinolone
      acetonide, triamcinolone acetonide, and dexamethasone are described. Finally,
      recently developed investigational particulate drug delivery systems in the form
      of liposomes, microspheres, and nanoparticles are examined.

PMID- 22988345
TI  - The EGF receptor and HER2 participate in TNF-alpha-dependent MAPK activation and
      IL-8 secretion in intestinal epithelial cells.
AB  - TNF-alpha activates multiple mitogen-activated protein kinase (MAPK) cascades in
      intestinal epithelial cells (IECs) leading to the secretion of interleukin 8 (IL
      8), a neutrophil chemoattractant and an angiogenic factor with tumor promoting
      properties. As the epidermal growth factor receptor (EGFR) is a known transducer
      of proliferative signals and a potent activator of MAPKs, we hypothesized that
      the EGFR participates in TNF-dependent MAPK activation and IL-8 secretion by
      intestinal epithelial cells (IECs). We show that the EGFR is tyrosine
      phosphorylated following treatment of IECs (HT-29 and IEC-6) with TNF-alpha. This
      requires EGFR autophosphorylation as it was blocked by the EGFR kinase inhibitor
      AG1478. Autophosphorylation was also inhibited by both a Src-kinase inhibitor and
      the metalloproteinase inhibitor batimastat. TNF treatment of IECs resulted in the
      accumulation of soluble TGF-alpha; treatment of IECs with batimastat suppressed
      TGF-alpha release and immunoneutralization of TGF-alpha resulted in decreased
      EGFR and ERK phosphorylations. TNF-alpha treatment of IECs resulted in an
      association between EGFR and HER2 and inhibition of HER2 using a specific
      inhibitor AG879 in combination with AG1478-suppressed TNF-alpha-dependent ERK
      phosphorylation and IL-8 release. Downregulation of HER2 via siRNA resulted in a
      significant decrease in ERK phosphorylation and a 50% reduction in IL-8
      secretion.

PMID- 22988347
TI  - Update of faecal markers of inflammation in children with cystic fibrosis.
AB  - There is evidence of intestinal inflammation in patients with CF. Intestinal
      inflammation may negatively impact the nutritional status of patient with CF,
      which adversely affects pulmonary function and survival. This paper provides an
      up-to-date review of intestinal inflammation in CF and an evaluation of utility
      of two specific faecal inflammatory markers (S100A12 and calprotectin).

PMID- 22988348
TI  - Arecanut as an emerging etiology of oral cancers in India.
AB  - Arecanut (AN) usage is widespread in Asian countries, especially India and
      Taiwan. The incidence of oral cancer is increasing day by day, but there is no
      exponential increase with tobacco usage. Especially in the country like Taiwan
      where betel quid mostly do not contain tobacco, AN can be correlated with the
      increased incidence of cancer. There are different studies in the literature
      about AN and oral cancer but none of them have concluded with the definite
      pathway for carcinogenesis. The present paper includes reviews of the literature
      for AN and oral cancer and summarizes the possible mechanisms associated with AN
      induced carcinogenesis; and we have also tried to propose pathway of
      carcinogenesis.

PMID- 22988346
TI  - Arginine-based inhibitors of nitric oxide synthase: therapeutic potential and
      challenges.
AB  - In the past three decades, nitric oxide has been well established as an important
      bioactive molecule implicated in regulation of cardiovascular, nervous, and
      immune systems. Therefore, it is not surprising that much effort has been made to
      find specific inhibitors of nitric oxide synthases (NOS), the enzymes responsible
      for production of nitric oxide. Among the many NOS inhibitors developed to date,
      inhibitors based on derivatives and analogues of arginine are of special
      interest, as this category includes a relatively high number of compounds with
      good potential for experimental as well as clinical application. Though this
      group of inhibitors covers early nonspecific compounds, modern drug design
      strategies such as biochemical screening and computer-aided drug design have
      provided NOS-isoform-specific inhibitors. With an emphasis on major advances in
      this field, a comprehensive list of inhibitors based on their structural
      characteristics is discussed in this paper. We provide a summary of their
      biochemical properties as well as their observed effects both in vitro and in
      vivo. Furthermore, we focus in particular on their pharmacology and use in recent
      clinical studies. The potential of newly designed specific NOS inhibitors
      developed by means of modern drug development strategies is highlighted.

PMID- 22988349
TI  - Current therapy and recent advances in the management of retinoblastoma.
AB  - Retinoblastoma is the most common intraocular malignancy in children. The
      survival of retinoblastoma patients and visual outcome has improved dramatically
      in the developed world. This can be attributed to early tumor recognition and
      advances in the management of retinoblastoma. Chemoreduction followed by adjuvant
      consolidative treatment has replaced external beam radiotherapy as the primary
      modality of treatment for intraocular retinoblastoma. Further, histopathological
      high-risk factors have been identified in enucleated eyes, allowing use of
      prophylactic chemotherapy to take care of possible micrometastasis. The survival
      in case of extraocular retinoblastoma is still low, and the reported survival
      rate ranges between 50% and 70%. In developing countries, the overall survival of
      retinoblastoma patients remains low, primarily due to a delayed presentation,
      resulting in larger proportions of extraocular disease compared with the
      developed world, where majority of the disease is intraocular. Greater efforts
      need to be directed toward early tumor recognition in order to improve the
      survival of retinoblastoma patients in the developing world. In this article, we
      provide an overview of the current clinical management of retinoblastoma.

PMID- 22988350
TI  - mTOR inhibition in management of advanced breast cancer.
AB  - The mTOR pathway is becoming increasingly important in several cancers including
      breast cancer. This review will focus on the role of its inhibition in the
      management of advanced breast cancer.

PMID- 22988351
TI  - Diarrhea in neutropenic children with cancer: An Egyptian center experience, with
      emphasis on neutropenic enterocolitis.
AB  - BACKGROUND: Diarrhea is a frequent complication in children with cancer who
      received intensive chemotheraputic regimens. It may be caused by several factors,
      neutropenic enterocolitis (NE) being the most serious. AIM: To study diarrhea in
      neutropenic cancer patients in the pediatric age group, with its underlying
      etiologies and risk factors, especially the bacterial causes, with special
      concern on NE. MATERIALS AND METHODS: This study was carried out at the Pediatric
      Hematology and Oncology Units, Zagazig University Hospitals, Egypt, from January
      2009 to September 2010. All children with malignant diseases who are <=12 years
      of age were included. Patients who were neutropenic (<500/ mm(3)) on admission or
      who became neutropenic during their stay in the hospital were monitored regularly
      (daily) for diarrhea. Neutropenic cancer patients with diarrhea were grouped into
      two groups: Group 1, with NE, and group 2, with neutropenic diarrhea rather than
      NE. On the first day of diarrhea, patients were subjected to complete blood
      count, blood cultures, stool microscopy and culture. Abdominal ultrasonography
      was carried out within 3 days of diarrhea. RESULTS: A total of 200 children <=12
      years old, suffering from different malignancies, with a total of 180 neutropenic
      episodes were followed. Diarrhea was observed in 100 episodes (55.5%). NE
      constituted 16% of these diarrheal episodes. All patients with NE had
      significantly more severe neutropenia, and this was of longer duration than the
      other group. All patients with NE were febrile, with 100% positive blood culture.
      Stool analysis diagnosed giardiasis in 4.8% of the non-NE patients and in none of
      the NE patients, while stool culture was positive in 75% of the NE patients
      compared with 40.5% of the other group. CONCLUSIONS: Diarrhea is a common
      complication in neutropenic cancer children. Gram negative bacteria and Candida
      are the most incriminated pathogens. Duration and severity of neutropenia carry a
      great risk for the development of NE.

PMID- 22988352
TI  - Study of histopathological features and proliferation markers in cases of Wilms'
      tumor.
AB  - CONTEXT: The spectrum of pediatric renal tumors is different from adult renal
      tumors, and Wilms' tumor (WT) forms the majority. The histological type and
      clinicopathological staging are the two important prognostic parameters. The role
      of newer prognostic factors is not clear. AIMS: This study was performed to
      analyze the histopathological spectrum of pediatric renal tumors and to study the
      expression of proliferation markers (Ki-67 and p53) in WT and correlate its
      expression in epithelial and blastema components in different stages. MATERIALS
      AND METHODS: Twenty-seven cases of pediatric renal tumors were collected over 2
      years. Hematoxylin-eosin staining was used for diagnosis. Immunostaining was
      performed for Ki-67 and p53. Ki-67 proliferation index (PI) and p53 expression
      were determined in each case and for the epithelial and blastema components
      separately. STATISTICAL ANALYSIS AND RESULTS: We had 20 cases of WT (74.1%),
      three cases of mesoblastic nephroma (11.1%), three cases of clear cell sarcoma
      (11.1%) and one case of rhabdoid tumor (3.7%). It was observed that the PI of the
      epithelial component (57.2%) was significantly higher than that of blastema
      (39.53%) in all stages. The PI in Stage II is significantly higher than that in
      Stage I. Statistical analysis could not be performed in Stages III and IV due to
      the small number of cases. p53 expression did not show any significant difference
      in the epithelial and blastema components. There was also no significant
      difference between the stages. CONCLUSION: In this study, we found the
      differences between PI of different tissue components of WT, with the epithelial
      component having a higher PI, which correlated with the stage of advancement of
      the disease.

PMID- 22988353
TI  - Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma.
AB  - CONTEXT: The diagnosis of papillary thyroid carcinoma (PTC) is based on nuclear
      features. These features may be present in focal areas in benign thyroid diseases
      and follicular adenoma (FA), leading to diagnostic difficulty. AIMS: To evaluate
      the expression and pattern of the distribution of cytokeratin 19 (CK19) in PTC
      and compare its reactivity with other neoplastic and non-neoplastic conditions to
      assess its potential as a useful marker for PTC. MATERIALS AND METHODS: Twenty
      two cases of papillary carcinoma (usual type, follicular and diffuse sclerosing
      variant), eight follicular adenomas, eight multinodular goiters (MNG) were
      collected for a period of two years and six months. Sections were taken from
      thyroidectomy specimens fixed in 10% buffered neutral formalin. Hematoxylin and
      eosin staining and immunohistochemical staining for CK19 were done using standard
      protocol. Results were semiquantitatively scored as follows: 1+ (<5% positively
      stained cells), 2+ (5-25%), 3+ (25-75%) and 4+ (>75%), and then analyzed.
      STATISTICAL ANALYSIS AND RESULTS: All 22 (100%) papillary carcinomas showed
      diffuse and strong (3+ and 4+) CK19 expression. Six out of eight (75%) FAs and
      four out of eight (50%) MNG were positive for CK19, but it was of weaker
      intensity (1+ and 2+) and focal in distribution. CONCLUSION: Focal CK19 staining
      may be found in benign disease, but diffuse and strong positivity is
      characteristic of PTC, which can be used in the diagnosis of PTC in lesions of
      equivocal morphological appearances.

PMID- 22988355
TI  - Spontaneous rupture of benign mediastinal teratoma: A report of two cases.
AB  - Benign mediastinal teratomas are commonly asymptomatic and seldom cause
      complications. Spontaneous rupture into the pleura is rare and cross-sectional
      imaging is crucial in its early detection and planning a proper surgical
      approach. We report two cases of spontaneous pulmonary and pleural rupture of
      benign mediastinal teratoma and discuss the imaging appearances.

PMID- 22988354
TI  - Guidelines for locoregional therapy in primary breast cancer in developing
      countries: The results of an expert panel at the 8(th) Annual Women's Cancer
      Initiative - Tata Memorial Hospital (WCI-TMH) Conference.
AB  - BACKGROUND: Limited guidelines exist for breast cancer management in developing
      countries. In this context, the Women's Cancer Initiative - Tata Memorial
      Hospital (WCI-TMH) organised its 8(th) Annual Conference to update guidelines in
      breast cancer. MATERIALS AND METHODS: Appropriately formulated guideline
      questions on each topic and subtopic in the surgical, radiation and systemic
      management of primary breast cancer were developed by the scientific committee
      and shared with the guest faculty of the Conference. Majority of the questions
      had multiple choice answers. The opinion of the audience, comprising academic and
      community oncologists, was electronically cumulated, followed by focussed
      presentations by eminent national and international experts on each topic. The
      guidelines were finally developed through an expert panel that voted on each
      guideline question after all talks had been delivered and audience opinion
      elicited. Separate panels were constituted for locoregional and systemic therapy
      in primary breast cancer. RESULTS: Based on the voting results of the expert
      panel, guidelines for locoregional therapy of breast cancer have been formulated.
      Voting patterns for each question are reported. CONCLUSIONS: The updated
      guidelines on locoregional management of primary breast cancer in the context of
      developing countries are presented in this article. These recommendations have
      been designed to allow centers in the developing world to improve the quality of
      care for breast cancer patients.

PMID- 22988357
TI  - PNET of kidney: Report of four cases.
AB  - Primitive neuroectodermal tumor (PNET) of kidney is a rare tumor of kidney with
      only a few published reports. We report here four cases of PNET of kidney in the
      age group between 30 and 50 years who had complaints of vague pain and lump in
      loin. Hematuria was present in one case. Imaging of all cases revealed renal
      mass. The pathologic findings were consistent with PNET in all cases-confirmed by
      immunohistochemistry with diffuse membrane positivity of tumor cells of CD99. We
      could not do fluorescent in situ hybridization to demonstrate EWS-FLI-1 gene
      fusion. Each case was in the advanced stage. However, after giving postoperative
      radiotherapy and chemotherapy patients are still alive. Reporting of these cases
      are important as we got them in a short span of 3 years. In view of its poor
      prognosis, aggressive nature and different therapeutic approach- renal PNET
      should be differentiated from other small blue round cell tumors like
      neuroblastoma, rhabdoid tumor of kidney, nephroblastoma, small cell carcinoma,
      synovial sarcoma (monophasic, poorly differentiated) and non-Hodgkin lymphoma
      (NHL) by immunohistochemistry, cytogenetic, and molecular genetics study to see
      the different gene rearrangements in NHL and 3p deletion in small cell carcinoma.

PMID- 22988356
TI  - Angiosarcoma of the scalp associated with Xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis
      associated with hypersensitivity to ultraviolet light due to defects in
      Deoxyribonucleic acid (DNA) repair. These patients have more than a 1000-fold
      increased risk of developing skin cancers. Although multiple cutaneous
      malignancies are common, the simultaneous occurrence of angiosarcoma and basal
      cell carcinoma is a rare phenomenon. We report a case of a 25-year-old male with
      XP with angiosarcoma scalp and basal cell carcinoma of face and occiput and
      discuss the treatment of this aggressive neoplasm with a review of the literature
      pertaining to it.

PMID- 22988358
TI  - Geriatric oncology: The need for a separate subspecialty.

PMID- 22988359
TI  - Glutathione-s-transferase and CYP1A1*2A polymorphisms in acute lymphoblastic
      leukemia patients.

PMID- 22988361
TI  - Norepinephrine supplemented with dobutamine or epinephrine for the cardiovascular
      support of patients with septic shock.
AB  - BACKGROUND AND AIMS: Sepsis management remains a great challenge for intensive
      care medicine. The aim of this study was to evaluate the effect of adding
      dobutamine versus epinephrine to norepinephrine in treating septic shock patients
      refractory to fluid therapy. MATERIALS AND METHODS: Sixty adult patients with the
      diagnosis of septic shock were included in this study. Norepinephrine infusion
      was started at a dose of 0.05 MUg/kg/min, and increased gradually up to 0.1
      MUg/kg/min. Upon reaching this dose, patients with mean arterial pressure <70
      mmHg were further divided randomly into two equal groups. In group I: the
      patients continued on norepinephrine and dobutamine was added at a starting dose
      of 3 MUg/kg/min and increased in increments of 2 MUg/kg/min up to 20 MUg/kg/min.
      In group II: the patients continued on norepinephrine and epinephrine was added
      in a starting dose of 0.05 MUg/kg/ min and increased in increments of 0.03
      MUg/kg/min up to 0.3 MUg/kg/min. RESULTS: Group II patients developed
      significantly better cardiovascular parameters, lower arterial pH and higher
      serum lactate and urine output; however, the 28-day mortality and major adverse
      effects were comparable in both groups. CONCLUSIONS: The addition of epinephrine
      to norepinephrine has positive effects on the cardiovascular parameters but
      negative results on the serum lactate concentration and systemic pH compared with
      the addition of dobutamine to norepinephrine.

PMID- 22988360
TI  - Low molecular weight heparin in prophylaxis of deep vein thrombosis in Asian
      general surgical patients: A Kashmir experience.
AB  - BACKGROUND AND OBJECTIVES: Deep vein thrombosis (DVT) occurs at a lower rate in
      Asia than in the rest of the world. We wanted to study the significance and
      efficacy of low molecular weight heparin (LMWH) in prophylaxis of DVT in major
      general surgical patients in the Kashmir Valley (India, Asia) so as to make it a
      routine in our patients. PATIENTS AND METHODS: This was a prospective study in
      which the effect of LMWH was compared with no prophylaxis. RESULTS: LMWHs are
      more effective than no prophylaxis in the prevention of DVT and pulmonary
      thromboembolism in highest-risk general surgical patients (odds ratio = 16.64;
      95% confidence interval = 3.63-1130.03; P-value = 0.014). CONCLUSION: LMWHs have
      a significant prophylactic effect on DVT in general surgical patients, with a
      higher benefit to risk ratio, and, in spite of the low incidence of DVT in Asia,
      its prophylaxis should routinely be considered in this part of the world as well,
      preferably in the form of LMWHs.

PMID- 22988362
TI  - Admission source and mortality in a pediatric intensive care unit.
AB  - BACKGROUND AND AIMS: Studies carried out in different countries have shown that
      source of patient admission in Intensive Care Units (ICUs) is associated to
      death. Patients admitted from wards show a greater ICU mortality. The aim of the
      present study was to investigate the association between admission source and
      outcome in a Pediatric Intensive Care Unit (PICU). MATERIALS AND METHODS: We
      studied all PICU admissions that took place between January 2002 and December
      2005 in a tertiary hospital in Brazil. The major outcome studied was death while
      in the PICU. The independent variable analyzed was admission source, defined
      either as pediatric emergency room (PER), wards, operating room (OR) of the same
      hospital or other sources. RESULTS: A total of 1823 admissions were studied. The
      overall expected mortality based on the Pediatric Index of Mortality 2 was 6.5%
      and the observed mortality was 10.3%. In adjusted analysis, the mortality was
      doubled in patients admitted from wards when compared with the PER patients.
      CONCLUSIONS: Observed mortality rates were higher in patients admitted from wards
      within the same hospital, even after adjustment.

PMID- 22988363
TI  - Percutaneous dilatational tracheostomy: Griggs guide wire dilating forceps
      technique versus ULTRA-perc single-stage dilator - A prospective randomized
      study.
AB  - Percutaneous dilatational tracheostomy (PDT) is a frequently performed surgical
      procedure on critically ill patients. This study was designed to compare its two
      methods: Griggs guide wire dilating forceps (GWDF) technique and the ULTRA-perc
      single-stage dilator technique MATERIALS AND METHODS: Thirty Intensive Care Unit
      (ICU) patients on prolonged mechanical ventilation and requiring tracheostomy
      were included in our prospective randomized study. The first group (GP-GWDF)
      underwent PDT by the GWDF technique and the second group by the ULTRA-perc
      technique (GP-UP). Time for the procedure and early and late procedural
      complications were recorded and compared in between the two groups. RESULTS: Time
      taken for tracheostomy was 11.68 +/- 6.48 min for GP-GWDF and 13.93 +/- 11.54 min
      for GP-UP (P-value 0.486). Desaturation was noted in two patients in GP-GWDF
      versus five in GP-UP (P-value = 0.195). Hypercapnea and rise in peak airway
      pressure occurred in one patient in GP-GWDF versus two in GP-UP (P-value =
      0.543). Loss of airway was recorded in two patients in GP-UP and in none in GP
      GWDF (P-value = 0.143). Subcutaneous emphysema, pneumothorax and
      pneumomediastinum occurred in one patient in GP-UP. No major complications were
      observed in GP-GWDF (P-value = 0.309). Hoarseness of voice was noted in one
      patient in each group (P-value = 0.659). CONCLUSION: Both the techniques seem to
      be equally reliable for carrying out PDT at bedside in the ICU.

PMID- 22988364
TI  - Isolated inhalational injury: Clinical course and outcomes in a multidisciplinary
      intensive care unit.
AB  - BACKGROUND AND AIMS: Although smoke inhalation is well known to cause acute lung
      injury, there are few reports in literature that study the evolution, clinical
      course and outcomes of isolated inhalational lung injury in a modern intensive
      care setting. A major fire disaster provided us the opportunity to study victims
      of isolated inhalational injury admitted to our Multidisciplinary Intensive Care
      Unit (MICU). MATERIALS AND METHODS: We studied the clinical course, ICU and
      hospital outcomes of 13 victims of a fire disaster who required mechanical
      ventilation for isolated inhalational lung injury. All patients were followed up
      at regular intervals, and their functional status was assessed at 8 months after
      hospital discharge. RESULTS: The Lung Injury Scores (LIS) worsened to reach a
      nadir on Day 3 of injury. There was a significant correlation between the LIS on
      Day 3 and duration of mechanical ventilation (r = 0.8; P = 0.003), ICU (r = 0.8;
      P = 0.002) and hospital (r = 0.6; P = 0.02) days. Late-onset airway complications
      were encountered in four patients. Three of them required long-term artificial
      airways - two with a tracheostomy while the third patient required surgical
      insertion of a "T" tube. Persistent problems with phonation occurred in two
      patients. At 8 months postdischarge, all patients were independent with
      activities of daily living; all were back to work, except for two who continued
      to need artificial airways. CONCLUSIONS: Inhalational lung injury progresses over
      the first few days and is worst after 72 h. Late-onset airway complications may
      manifest after several weeks and require repeated intervention.

PMID- 22988365
TI  - An audit of characteristics and outcomes in adult intensive care patients
      following tracheostomy.
AB  - BACKGROUND: Tracheostomies are commonly performed on critically ill patients
      requiring prolonged mechanical ventilation. The purpose of this study was to
      review our experience with surgical and percutaneous tracheostomies and identify
      factors affecting outcome. MATERIALS AND METHODS: Patients who underwent
      tracheostomy between January 1999 and June 2008 were identified on the basis of
      Diagnostic Related Group coding and the International Statistical Classification
      of Diseases and Related Health Problems, Tenth Revision, Australian Modification
      procedural code. The primary endpoint was in-hospital mortality. Contingency
      tables were generated for clinical variables and a chi-squared test was used to
      determine significance. RESULTS: One hundred and sixty-eight patients underwent
      tracheostomy between January 1999 and 30 June 2008. In-hospital mortality was
      22.6%. The probability of death was found to be independent of timing of
      tracheostomy, technique used (percutaneous vs. surgical), number of failed
      extubations and obesity. On univariate analysis, the null hypothesis of
      independence was rejected for age on admission (P = 0.014), diagnosis of sepsis
      (P = 0.0008) or cardiac arrest (P = 0.0016), Acute Physiology and Chronic Health
      Evaluation II score (P = 0.0319) and the Australasian Outcomes Research Tool for
      Intensive Care calculated risk of death (P = 0.0432). CONCLUSION: Although a
      number of patient factors are associated with worse outcome, tracheostomy appears
      to be a relatively safe technique in the Intensive Care Unit population.

PMID- 22988366
TI  - A sound sleep.
AB  - Benzodiazepine is a commonly encountered agent of poisoning, which is readily
      diagnosed by a pertinent history of drug ingestion and the clinical scenario. In
      the absence of a proper drug history, the diagnosis becomes challenging. Proper
      clinical assessment, urine assays and imaging play a very important role in
      reaching the diagnosis. We present a case of acute benzodiazepine poisoning
      without a history of drug intake. The key pointers toward diagnosis were an
      unarousable state with obstructive apnea. Magnetic resonance imaging (MRI) of the
      brain revealed peculiar symmetrical isolated globus pallidus T2 hyperintensity.
      We believe this to be the first report of isolated bilateral basal ganglia T2
      weighted hyperintensity in MRI in the setting of acute benzodiazepine poisoning
      from India.

PMID- 22988367
TI  - Severe arrhythmia after lithium intoxication in a patient with bipolar disorder
      admitted to the intensive care unit.
AB  - Despite its narrow therapeutic index, lithium remains widely used as a mood
      stabilizer for the treatment of bipolar disease. The cardiac side-effects of
      lithium have been well documented, and may induce non-specific T-wave flattening,
      prolonged QT interval, sinus node dysfunction and also ventricular tachycardia
      and ventricular fibrillation. We report the case of a 61-year-old male patient
      diagnosed with bipolar disorder who developed life-threatening cardiac
      manifestations secondary to severe lithium poisoning. Although hemodialysis was
      performed and the arrhythmias were adequately treated, the patient died on the
      sixth day after hospital admission due hemorrhagic complications after
      tracheostomy.

PMID- 22988368
TI  - Hot climate and perioperative outcome: Relationship?

PMID- 22988369
TI  - Patient communication in intensive care unit.

PMID- 22988370
TI  - Pseudoleukopenia due to ethylenediaminetetraacetate induced leukoagg-lutination
      in a case of hypovolemic shock.

PMID- 22988371
TI  - Loss of dialysis catheter guide-wire: How to prevent?

PMID- 22988372
TI  - Inadvertent insertion of nasogastric tube into the trachea of a conscious
      patient.

PMID- 22988373
TI  - Advanced cardiac life support training program on the outcome of cardiopulmonary
      resuscitation in a tertiary care hospital: Real scenario.

PMID- 22988374
TI  - A simple method to prevent devastating complications.

PMID- 22988375
TI  - Cartap poisoning: Additional thoughts.

PMID- 22988376
TI  - Hemovigilance and blood safety.

PMID- 22988377
TI  - Visual inspection of platelet concentrates; still an essential prerelease check.

PMID- 22988378
TI  - Automation in immunohematology.
AB  - There have been rapid technological advances in blood banking in South Asian
      region over the past decade with an increasing emphasis on quality and safety of
      blood products. The conventional test tube technique has given way to newer
      techniques such as column agglutination technique, solid phase red cell adherence
      assay, and erythrocyte-magnetized technique. These new technologies are adaptable
      to automation and major manufacturers in this field have come up with semi and
      fully automated equipments for immunohematology tests in the blood bank.
      Automation improves the objectivity and reproducibility of tests. It reduces
      human errors in patient identification and transcription errors. Documentation
      and traceability of tests, reagents and processes and archiving of results is
      another major advantage of automation. Shifting from manual methods to automation
      is a major undertaking for any transfusion service to provide quality patient
      care with lesser turnaround time for their ever increasing workload. This article
      discusses the various issues involved in the process.

PMID- 22988379
TI  - Code development of the national hemovigilance system and expansion strategies
      for hospital blood banks.
AB  - OBJECTIVES: The aims of this study were to develop reportable event codes that
      are applicable to the national hemovigilance systems for hospital blood banks,
      and to present expansion strategies for the blood banks. MATERIALS AND METHODS:
      The data were obtained from a literature review and expert consultation, followed
      by adding to and revising the established hemovigilance code system and
      guidelines to develop reportable event codes for hospital blood banks. The
      Medical Error Reporting System-Transfusion Medicine developed in the US and other
      codes of reportable events were added to the Korean version of the Biologic
      Products Deviation Report (BPDR) developed by the Korean Red Cross Blood Safety
      Administration, then using these codes, mapping work was conducted. We deduced
      outcomes suitable for practice, referred to the results of the advisory councils,
      and conducted a survey with experts and blood banks practitioners. RESULTS: We
      developed reportable event codes that were applicable to hospital blood banks and
      could cover blood safety - from blood product safety to blood transfusion safety 
      and also presented expansion strategies for hospital blood banks. CONCLUSION: It
      was necessary to add 10 major categories to the blood transfusion safety stage
      and 97 reportable event codes to the blood safety stage. Contextualized solutions
      were presented on 9 categories of expansion strategies of hemovigilance system
      for the hospital blood banks.

PMID- 22988380
TI  - A prospective study for prevalence and/or development of transfusion-transmitted
      infections in multiply transfused thalassemia major patients.
AB  - OBJECTIVE: To evaluate the rate of seropositivity to hepatitis B and C and Human
      Immunodeficiency Virus (HIV) infections among children with beta-thalassemia
      major receiving multiple transfusions in Ahmedabad, India, compared with healthy
      controls. MATERIALS AND METHODS: The study was performed during January 2007 to
      January 2009 on multi-transfused children suffering with beta-thalassemia major
      registered in the Prathama Blood Centre, Ahmedabad; Jeevandeep hospital,
      Ahmedabad; and Red Cross Blood Centre, Ahmedabad, and investigated for the
      prevalence and development of transfusion-transmitted infections. Hepatitis B
      surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV) Antibodies (Ab), and HIV Ab
      were checked using a fourth-generation Enzyme-Linked Immunosorbent Assay (ELISA).
      Positive tests were confirmed by western blots. Healthy blood donors were used
      for the control group. RESULTS: Hepatitis B surface antigen, anti-HCV Ab, and HIV
      Ab were positive in one of 96 (1.04%; 95% Confidence Interval (CI) = 0.17-1.3),
      24 of 96 (25%; 95% CI = 11.4-14.2), and one of 96 (1.04%; 95% CI = 0.12-1.3),
      respectively. The rate of anti-HCV Ab was significantly higher in multi
      transfused children suffering with beta-thalassemia major. In thalassemia
      patients, the rate of positive anti-HCV Ab was significantly higher than that for
      positive HBsAg (P<0.001) and HIV Ab (P<0.001). CONCLUSION: It is concluded that
      HCV is the current major problem in multi-transfused children with thalassemia
      major and more careful pretransfusion screening of blood for anti-HCV must be
      introduced in blood centers.

PMID- 22988381
TI  - Analysis of adverse events and predisposing factors in voluntary and replacement
      whole blood donors: A study from north India.
AB  - BACKGROUND: Lack of awareness and community motivation, compounded with
      fragmented blood transfusion services in our country, Often leads to shortage of
      blood. Donor recruitment and retention are essential for ensuring adequate blood
      supply. However, adverse events (AEs) in donors have a negative impact on donor
      return. AIMS AND OBJECTIVES: The present study was aimed to assess the frequency
      of AEs in whole blood donors and analyze the predisposing factors for AEs.
      MATERIAL AND METHODS: The study was conducted on allogeneic whole blood donors
      over a period of 14 months, i.e., from January 2002 to February 2003. A total of
      37,896 donors were monitored for any AEs: 22587 (59.6%) were voluntary donors
      (VD) and 15,309 (40.4%) were replacement donors (RD). RESULTS: Overall reaction
      rate was 2.5% with vasovagal reactions constituting 63.5% and hematomas 35.0% of
      all reactions. Vasovagal reactions showed a significant association with young
      age, lower weight, first time donation status, female gender, and nature of blood
      donation camps. Amongst male donors, RDs had more reactions (P=0.03) than VDs.
      Majority of donors (85%) with vasovagal reactions admitted to some fear or
      anxiety prior to donation. Hematoma formation occurred significantly more when
      less trained staff performed phlebotomy. CONCLUSION: Donor safety is an essential
      prerequisite to increase voluntary blood donation. AE analysis helps in
      identifying the blood donors at risk of donor reactions and adopting appropriate
      donor motivational strategies, pre-donation counseling, and care during and after
      donation.

PMID- 22988382
TI  - Neonatal thrombocytopenia and platelets transfusion.
AB  - BACKGROUND: Neonates often develop thrombocytopenia at some time during hospital
      stay. Platelet transfusion are frequently given to them and are likely to result
      in unnecessary transfusion. MATERIAL AND METHODS: Thus, we analyzed
      thrombocytopenia in neonates, its prevalence, and relationship if any, between
      clinical condition and platelet transfusion in neonates, which would have been
      helpful in developing guidelines and/or protocols for platelet transfusion (and
      reducing the donor exposure) in neonates. RESULTS: A total of 870 neonates who
      were admitted in Neonatal Intensive Care Unit (NICU) with various morbidities had
      platelets count done; of these, 146 (16.7%) neonate revealed thrombocytopenia.
      DISCUSSION: Low birth weight babies (P 0.009) and babies born with mother having
      hypertension (P 0.04) showed significant thrombocytopenia. Neonates with
      intrauterine growth retardation (IUGR) diagnosed during antenatal screening
      showed lower platelet count (P 0.022). Neonates having associated illness, such
      as sepsis, gastrointestinal, and respiratory problems, and on vasopressor drugs
      were found to be associated with low platelet count. CONCLUSION: In our study,
      16.40% of thrombocytopenic neonates required platelet transfusion either alone or
      with other blood component during their stay in NICU.

PMID- 22988383
TI  - True positivity of anti-Hepatitis C Virus Enzyme-linked immunosorbent assay
      reactive blood donors: A prospective study done in western India.
AB  - BACKGROUND: A significant number of safe donations are removed from the blood
      supply, because of the reactive anti-HCV screening test results. This study aimed
      to assess if the HCV (Hepatitis C Virus) seropositive donors were confirmed
      positive or not. MATERIALS AND METHODS: More than 68,000 blood donors' samples
      were routinely screened and 140 samples were found to be anti-HCV ELISA reactive.
      These 140 samples were tested by NAT. The NAT negative samples were tested by
      RIBA. Analysis of samples reactive in single ELISA kit vs. two ELISA kits was
      done. RESULTS: Out of 140 anti-HCV ELISA reactive samples, a total of 16 (11.43%)
      were positive by NAT. The results of 124 RIBA showed 6 (4.84%) positive, 92
      (74.19%) negative, and 26 (20.97%) indeterminate results. None of the sample
      which was reactive in only single ELISA kit was positive by NAT or RIBA.
      CONCLUSION: Only a minority of blood donors with repeatedly reactive anti-HCV
      screening test is positive by confirmatory testing, but all these blood units are
      discarded as per existing legal provisions in India. Efforts should be made to
      retain these donors and also donor units.

PMID- 22988384
TI  - Effectiveness of blood donor questionnaire directed at risk factor for
      transfusion transmitted infections in Pakistani population.
AB  - BACKGROUND: Deferring blood donors who admit to high-risk behavior on questioning
      are likely to eliminate those in window period for transfusion transmitted
      infections (TTI). However, many questions have been implemented in some countries
      as part of donor history questionnaire, based on precautionary principle and not
      on evidence, and can result in increased donor losses. This study aims to
      identify effective risk-directed questions having high predictive value, in local
      context which can form part of blood donor deferral policies. For this, a case
      control study in a hospital blood bank having donation services was carried out
      prospectively over a period of three years. MATERIALS AND METHODS: Two hundred
      and twenty donors, who were repeatedly reactive for HBsAg, anti-HCV, anti-HIV
      with EIA, and syphilis with TPHA, were the cases. Eight hundred and eighty four
      controls were the donors who tested negative for all TTI test. All donors
      answered seven hepatitis risk directed questions and their responses and
      reactivity status for TTI were used for statistical analysis with SPSS ver. 15.
      RESULTS: Positive predictive value for history of jaundice at any age for HBsAg
      was 20%, while PPV for history of surgery in previous six months for both HBsAg
      and anti-HCVHCV was also around 20%, based on pretest probability of 7%. The post
      test probability for these questions was around 30%. Odds ratios with 95% CI did
      not reveal any significant association of hepatitis with any of seven questions.
      Donor losses after deferring on basis of two questions were 5.3% per year, while
      deferral rate after all seven questions was 20%. CONCLUSIONS: Donors should be
      permanently deferred if there is history of jaundice at any age, while deferral
      period after surgery should be one year. Other risk-directed questions should not
      be used to defer donors. Donor deferral policies should be evidence based and
      questions with proven efficacy should be made part of donor history questionnaire
      to minimize donor losses.

PMID- 22988385
TI  - Seroprevalence of malaria in blood donors and multi-transfused patients in
      Northern India: Relevance to prevention of transfusion-transmissible malaria.
AB  - BACKGROUND: Transfusion-transmissible malaria (TTM) is a major concern in malaria
      endemic countries. A study was therefore conducted to know sero-prevalence of
      malaria in blood donors and the risk of TTM to multi-transfused patients at our
      hospital. MATERIALS AND METHODS: STUDY SUBJECTS WERE: eligible blood donors (n =
      1000), donors deferred due to history of fever in the last 3 months (n = 100),
      and multi-transfused patients (n = 200). Screening for malaria was done by slide
      microscopy, immunochromatographic rapid diagnostic test (RDT) for malaria
      antigen, and anti-malaria antibody by enzyme linked immunosorbent assay. RESULTS:
      Malaria antibody prevalence in eligible donors and donors with history of fever,
      thalassemia patients, and in other multi-transfused patients was 16.9%, 22%, 6%,
      and 15%, respectively. None of the donors were positive for malaria on
      microscopic examination. None of the blood donors except one donor with history
      of fever, tested positive with RDT. CONCLUSION: Malaria antibody prevalence in
      blood donors at our center is high. As blood units donated by such donors have
      high-risk potential, special processing may be undertaken to reduce the risk of
      TTM.

PMID- 22988386
TI  - Deferral pattern in voluntary blood donors on basis of low hemoglobin and effect
      of application of digital hemoglobinometer on this pattern.
AB  - BACKGROUND: One of the responsibilities of blood center is to provide safety to
      blood donors. It is mandatory to screen a blood donor for hemoglobin (Hb) or
      hematocrit which should not be less than 12.5 g/dl or 38% Hct. Most commonly
      applied method for hemoglobin estimation is copper sulphate method, but this
      method has chances of false acceptance as well as false deferral. In order to
      avoid this chance of error, digital hemoglobinometer is used. This study was
      planned to analyze effect of application of digital hemoglobinometer for
      detection of Hb on donors, who are deferred by copper sulphate method. MATERIALS
      AND METHODS: Total 35,339 voluntary non renumareted altruistic donors were
      included in this study between the periods of September 2005 to July 2006. Total
      deferred donors were 8622 (24.39%) and donors deferred due to hemoglobin by
      copper sulphate method were 4391 (50.92%). Digital hemoglobinometer was applied
      on 3163 deferred donors (72.03%). Results of digital hemoglobinometer were
      validated by known controls. RESULT: Digital hemoglobinometer was applied on 3163
      donors who were deferred by copper sulphate method. Out of this, donors accepted
      by digital hemoglobinometer were 1196 (37.01%). Total repeat donors were 629
      (52.50%) and first time were 567 (47.40%). Male donors were 891 (74.44%) and
      females were 305 (25.50%). Donors deferred with digital hemoglobinometer were
      2135, out of them 1097 (51.14%) were repeat, 1038 (48.38%) were first time, 1349
      (60.79%) were male, 786 (34.47%) donors were female donors. Range of hemoglobin
      in deferred donors was 7.0 to 12.4 and in accepted donors 12.5 to 16.4.
      CONCLUSION: By the application of digital hemoglobinometer 37.81% donors were
      found hemoglobin >12.5 which were deferred with copper sulphate method and
      unnecessary deferral of donors can be reduced to a great extent. In country like
      India, where blood supply is always less than the requirement, this new technique
      may be helpful to increase donor population but cost benefit ratio should be
      analyzed.

PMID- 22988387
TI  - Expanding role of a blood center.
AB  - MATERIALS AND METHODS: The study was performed on prospective donors who reported
      to the Department of Transfusion Medicine. Individuals deferred due to
      hypertension contributed the study population. They were compared with age and
      sex matched donor controls. Demographic details were recorded in a proforma. On
      identification of a hypertensive individual, consequent two comparable donors
      were taken as controls with a total of 50 hypertensive subjects. Hypertensive
      status of the subjects were assessed based on the criteria formulated by the WHO
      ISH and US Seventh Joint National Committee report on prevention, detection,
      evaluation and treatment of high blood pressure. RESULTS: About 0.95% of healthy
      blood donors had undetected hypertension. Mean age at detection of hypertension
      in the study group was 35.44 +/- 7.69 years. Higher BMI was observed in the
      hypertensive group compared to normotensive control group with P value
      significant at 0.0001. CONCLUSION: About 1% of healthy individuals were found to
      have undetected hypertension. Though the study was not designed to determine the
      prevalence of hypertension in the region, it is a rough estimate of the
      proportion of undetected hypertension in the local population as donors are
      considered as representative of healthy population.

PMID- 22988388
TI  - Hemolytic disease of fetus and newborn due to anti-E alloantibody in a newborn of
      Rh (D)-positive mother.

PMID- 22988390
TI  - Audit of use of blood and its components in a tertiary care center in South
      India.

PMID- 22988389
TI  - IgA-induced autoimmune hemolytic anemia in a patient with antiphospholipid
      syndrome.

PMID- 22988391
TI  - Ahead to 100% of voluntary nonremunerated blood donation at a tertiary referral
      hospital blood bank in South India.

PMID- 22988392
TI  - Effective implementation of regulations and facilitation in improving blood
      transfusion services in Gujarat state.

PMID- 22988393
TI  - Rapid decreasing of transfused platelet in a cancerous patient: Anti-platelet
      antibody.

PMID- 22988394
TI  - Blood cell MicroRNAs and blood product safety.

PMID- 22988395
TI  - Role of transfusion medicine in post-crisis nuclear leakage.

PMID- 22988396
TI  - What's New in Emergencies Trauma and Shock? Studying glasgow outcome scores at
      discharge and final outcomes in severe head injury.

PMID- 22988397
TI  - Interval appendectomy in adults: A necessary evil?
AB  - The management of appendiceal mass remains a matter of major controversy in the
      current literature. Currently, initial nonoperative management followed by
      interval appendectomy is favored over immediate appendicectomy. However, the
      necessity of doing an interval appendectomy has been questioned - is it a
      necessary evil? The present review revisits the above controversy, evaluates the
      current literature, assesses the need for interval appendectomy in adults, and
      provides recommendations.

PMID- 22988398
TI  - Can glasgow score at discharge represent final outcome in severe head injury?
AB  - BACKGROUND: Patients with head injury continue to improve over time and a minimum
      follow-up of six months is considered necessary to evaluate outcome. However,
      this may be difficult to assess due to lack of follow-up. It is also well known
      that operated patients who return for cranioplasty usually have the best outcome.
      AIMS AND OBJECTIVES: To assess the outcome following severe head injury using
      cranioplasty as a surrogate marker for good outcome. MATERIALS AND METHODS: This
      was a retrospective study carried out from January 2009 to December 2010. All
      patients with severe head injury who underwent decompressive craniectomy (DC) in
      the study period were included. Patients who came back for cranioplasty in the
      same period were also included. Case records, imaging and follow up visit data
      from all patients were reviewed. Glasgow Coma Score (GCS) on admission and
      Glasgow Outcome Score (GOS) at discharge were assessed. OBSERVATIONS AND RESULTS:
      Of the 273 patients, 84.25% (n=230) were males and 15.75% (n= 43) were females.
      The mean age was 34.3 years (range 2-81 years, SD 16.817). The mean GCS on
      admission was 5.615 (range 3-8, SD 1.438). The in-hospital mortality was 54%
      (n=149). Good outcome (GOS of 4 or 5) at discharge was attained in 22% (n=60)
      patients. Sixty five patients returned for cranioplasty (with a GOS of 4 or 5)
      during the study period. There was no statistical difference in the number of
      patients discharged with good outcome and those coming back for cranioplasty in
      the study period (P>0.5). Patients who came back for cranioplasty were younger in
      age (mean age 28.815 years SD 13.396) with better admission GCS prior to DC (mean
      GCS 6.32 SD1.39). CONCLUSIONS: In operated severe head injury patients
      significant number of patients (24% in our study) have excellent outcome.
      However, insignificant number of patients had further improvement to GOS 4 or 5
      (good outcome) from the time of initial discharge. This suggests that due to lack
      of intensive rehabilitative facilities, GOS at discharge may be representative of
      final outcome in the vast majority of cases of severe head injury in developing
      countries like India.

PMID- 22988400
TI  - Non-fatal suicide attempt by intentional stab wound: Clinical management,
      psychiatric assessment, and multidisciplinary considerations.
AB  - BACKGROUND: Suicide by means of self-inflicted stab wounds is relatively uncommon
      and little is known about this population and their management. MATERIALS AND
      METHODS: Retrospective review of adult trauma patients admitted to our Level-1
      trauma center between January 2005 and October 2009 for management of non-fatal,
      self-inflicted stab wounds. RESULTS: Fifty-eight patients were evaluated with
      self-inflicted stab wounds. Four patients died due to their injuries (mortality,
      7%). Of the non-fatal stab wounds, 78% were male ranging in age from 19-82 (mean:
      45 years). The most common injury sites were the abdomen (46%), neck (33%), and
      chest (20%). In terms of operative interventions, 56% of abdominal operations
      were therapeutic, whereas 100% of neck and chest operations were therapeutic.
      When assessing for suicidal ideation, 44 patients (81%) admitted to suicidal
      intentions whereas 10 patients (19%) described accidental circumstances.
      Following psychiatric evaluation, 8 of the 10 patients with "accidental injuries"
      were found to be suicidal. Overall, 54 patients (98%) met criteria for a formal
      psychiatric diagnosis with 48 patients (89%) necessitating inpatient or
      outpatient psychiatric assistance at discharge. CONCLUSIONS: Compared to previous
      reports of stab wounds among trauma patients, patients with self- inflicted stab
      wounds may have a higher incidence of operative interventions and significant
      injuries depending on the stab location. When circumstances surrounding a self
      inflicted stabbing are suspicious, additional interviews by psychiatric care
      providers may uncover a suicidal basis to the event. Given the increased
      incidence of psychiatric illness in this population, it is imperative to approach
      the suicidal patient in a multidisciplinary fashion.

PMID- 22988399
TI  - Pediatric emergency medical services and their drawbacks.
AB  - AIM: To survey the literature on Pediatric Emergency Medical Services (PEMS) with
      an aim to focus its drawbacks and emphasize the means of improvement. MATERIALS
      AND METHODS: Published articles selected for inclusion were based on the
      significance and understanding of literature search on different aspects of PEMS.
      To meet this criterion, PubMed, PubMed Central, Science Direct, Uptodate, Med
      Line, comprehensive databases, Cochrane library and the Internet (Google, Yahoo)
      were thoroughly searched. RESULTS: PEMS provide out-of-hospital medical care
      and/or transport the patients to definitive care. The task force represents
      specialties of ambulance transport, first aid, emergency medical care, life
      saving, trauma, emergency medicine, water rescue, and extrication. Preliminary
      care is undertaken to save the patients from different medical exigencies. The
      techniques and procedures of basic and advanced life-support are employed. A
      large number of weaknesses are recorded in PEMS system, such as ambulance
      transport irregularities, deficit equipment, lack of expertise, and ignorance of
      the pre-hospital care providers. These are discussed with special reference to a
      few examples of medical exigencies. CONCLUSIONS: The appointments in PEMS should
      be regularized with specific qualifications, experience, and expertise in
      different areas. Responsibility of PEMS should not be left to pre-hospital care
      providers, who are non clinicians and lack proper education and training.
      Pediatricians should be adequately trained to play an active role in PEMS.
      Meetings should be convened to discuss the lapses and means of improvement.
      Networks of co-operation between pre-hospital providers and experts in the
      emergency department should be established.

PMID- 22988401
TI  - Utility of admission physiology in the surgical triage of isolated ballistic
      battlefield torso trauma.
AB  - BACKGROUND: An assessment of hemodynamic stability is central to surgical
      decision-making in the management of battlefield ballistic torso trauma (BBTT).
      AIMS: To analyse the utility of admission physiological parameters in
      characterising hemodynamic stability. SETTINGS AND DESIGN: A retrospective
      analysis of consecutive admissions, with BBTT, to forward surgical facility in
      Afghanistan. MATERIALS AND METHODS: The cohorts' admission physiology, need for
      operative intervention, and mortality data were collected retrospectively. The
      cohort was divided into patients requiring surgery for Life-Threatening Torso
      Hemorrhage (LTTH) and those not requiring immediate surgery (non-LTTH).
      STATISTICAL ANALYSIS: Parameters were compared using two sample t tests, Mann
      Whitney, Fisher's exact, and Chi-square tests. Receiver operator characteristic
      curves were used to identify significant parameters and determine optimum cut-off
      values. RESULTS: A total of 103 patients with isolated BBTT were identified: 44
      in the LTTH group and 59 in the non-LTTH group. The mean New Injury Severity
      Score +/- Standard Deviation (NISS+/-SD) was 28+/-14 and 13+/-12, respectively.
      The heart rate, systolic blood pressure (SBP), pulse pressure, shock index
      (SI=heart rate/SBP) and base excess were analysed. SI correlated best with the
      need for surgical torso hemorrhage control, P<0.05. An optimal cut-off of 0.9 was
      identified, producing a positive and negative predictive value of 81% and 82%,
      respectively. CONCLUSIONS: Shock index (SI) is a useful parameter for helping
      military surgeons triage BBTT, identifying patients requiring operative torso
      hemorrhage control. SI performance requires a normal physiological response to
      hypovolemia, and thus should always be considered in clinical context.

PMID- 22988402
TI  - The epidemiological findings and characteristic ground glass appearance on chest
      CT among patients with blunt lung injury.
AB  - AIM: To clarify the epidemiological findings and characteristics of ground glass
      lesions on chest computed tomography (CT) after blunt trauma. SETTING AND DESIGN:
      A medical college hospital and retrospective study. MATERIALS AND METHODS: We
      retrospectively investigated all blunt chest trauma patients who were admitted
      from January 2004 to December 2010. The inclusion criteria were patients with:
      (1) chest CT examination on arrival, (2) intrathoracic traumatic lesions
      confirmed by initial CT, and (3) a second chest CT examination within 7 days from
      admission. We divided the subjects into two groups. A GG group included subjects
      who had ground glass lesions on initial chest CT and a control group included
      subjects who did not have the ground glass appearance. RESULTS: The average age
      in the GG group was significantly lesser than that in the control group. The
      ratio of improvement for the value of SpO(2)/FiO(2) between on arrival and the
      second hospital day and ratio of improvement for CT findings between on arrival
      and the second CT examination in the GG group was greater than in the control
      group. CONCLUSION: The ground glass appearance on chest CT after blunt trauma was
      not rare, and the patients with ground glass lesions were younger and tended to
      have a better improvement of oxygenation and CT images in comparison with the
      patients without these characteristic lesions.

PMID- 22988403
TI  - Difficult nasoendotracheal intubation in a patient with severe maxillofacial
      trauma.
AB  - Dental occlusion is key point for proper maxillofacial reconstruction. In this
      way nasal airway management is extremely important for both oral and
      maxillofacial surgeons and anesthesiologists. We report a challenging case with
      severe maxillofacial trauma and nasal obstruction that it managed with a novel
      anesthetic - surgical procedure.

PMID- 22988405
TI  - Post traumatic arachnoiditis ossificans.
AB  - Arachnoiditis ossificans is a rare chronic disorder characterized by the presence
      of calcification/ ossification of the spinal arachnoid. We describe the computed
      tomography (CT) and magnetic resonance imaging (MRI) findings of arachnoiditis
      ossificans as sequelae to trauma in a 30-year-old patient. This imaging diagnosis
      becomes important to alert the clinician as most of them can be treated by
      conservative management.

PMID- 22988404
TI  - Thermometry in children.
AB  - Accurate measurement of temperature is important for detection of fever and
      hypothermia in pediatric patients. Ideal temperature-measurement technique should
      be safe, easy, noninvasive, cost effective, time efficient, and should precisely
      reflect core body temperature. Pulmonary artery is the closest to hypothalamus
      and best reflects the core temperature. Other sites used are distal esophagus,
      urinary bladder and nasopharynx. All these methods are invasive and difficult to
      use in clinical practice. Amongst the noninvasive methods, rectal thermometry is
      considered to be the closest to core temperature, but it has its own drawbacks.
      With the current evidence available, tympanic artery thermometry for children
      more than 2 years of age and temporal artery thermometry in all age groups are
      taking precedence over other methods.

PMID- 22988406
TI  - Manure pit injuries: Rare, deadly, and preventable.
AB  - A male worker entered an underground manure pit and lost consciousness. His
      coworker tried to rescue him and also lost consciousness in the pit. Emergency
      service arrived in minutes and removed both of them from the pit. Both men
      suffered anoxic brain injury and died in the hospital. Cases from Iowa Fatality
      Assessment and Control Evaluation Program Data Base program were reviewed.
      Occupational mortality rate was found to be 7.4 per 10,000 per year for
      occupational deaths related to agriculture compared to 3.1 per 10,000 per year
      for deaths not related to agriculture. In most of the cases associated with
      sewage or livestock waste handling, victims died of asphyxiation. While manure
      pit injury is rare, it has an extremely high fatality rate. The most effective
      strategy to decrease mortality is active prevention.

PMID- 22988407
TI  - Anaphylaxis related to fentanyl citrate.
AB  - Anaphylaxis is a fulminant, unexpected, immunoglobulin E-mediated allergic
      reaction that can be triggered by multiple agents. Common causative agents
      include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics,
      and opioids. Fentanyl citrate, however, is an extremely unusual cause of
      anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a
      prominent feature, as was in one of the patient. An adverse drug reaction is a
      noxious or unintended reaction to a drug that is administered in standard doses
      by the proper route for the purpose of prophylaxis, diagnosis, or treatment.
      Reactions are classified into two major subtypes: type A, which are dose
      dependent and predictable; and type B, which are not dose dependent and
      unpredictable. Unpredictable reactions include immune (allergic) or no immune
      drug hypersensitivity reactions and are related to genetic susceptibilities or
      undefined mechanisms (formally called idiosyncratic and intolerance reactions). A
      drug allergy is always associated with an immune mechanism for which evidence of
      drug-specific antibodies or activated T lymphocytes can be shown. In the last few
      years, many novel drugs have entered clinical practice (i.e., biologic agents)
      generating novel patterns of drug hypersensitivity reactions. As old drugs
      continue to be used, new clinical and biologic techniques enable improvement in
      the diagnosis of these reactions.

PMID- 22988408
TI  - Aorto-esophageal fistula secondary to penetrating atherosclerotic ulcer.
AB  - Aorto-esophageal fistula (AEF) is a rare and life threatening condition, which
      can be rapidly fatal. More than half of such cases are secondary to aortic
      aneurysm rupture. There are only two previous reports describing AEF caused by
      penetrating atherosclerotic ulcer. We present multidetector computed tomography
      findings in a case of AEF secondary to penetrating atherosclerotic ulcer.

PMID- 22988409
TI  - Diagnosis of congenital broncho-esophageal fistula in a 62-year-old male.
AB  - Congenital broncho-esophageal fistula (BEF) may go unrecognized in infancy and
      childhood and present later in life, due to non specific signs and symptoms. We
      report an adult case of congenital BEF which was diagnosed after massive
      aspiration precipitated by raised intra abdominal pressure due to severe acute
      pancreatitis.

PMID- 22988410
TI  - Using thrombolytics in frostbite injury.
AB  - Until recently, the treatment of frostbite injuries has been limited to
      supportive care only, with mediocre outcomes. The use of thrombolytic therapy has
      been presented in a limited fashion in the literature since 2005. This case study
      describes the work-up and treatment of a patient with severe frostbite injury who
      received tPA. We then discuss thrombolytic therapy in more detail, with
      particular attention to the two studies outlining different treatment regimens.

PMID- 22988411
TI  - Pulmonary cement embolism after pedicle screw vertebral stabilization.
AB  - Pulmonary arterial embolization of polymethylmethacrylate cement, most usually
      occurring after vertebroplasty or kyphoplasty, is very uncommon following
      vertebral stabilization procedures. Unenhanced CT scans viewed at lung window
      settings allow confident identification of cement emboli in the pulmonary
      circulation along with possible associate parenchymal changes, whereas hyperdense
      emboli may be less conspicuous on CT-angiographic studies with high-flow contrast
      medium injection. Although clinical manifestations are largely variable from
      asymptomatic cases to severe respiratory distress, most cases are treated with
      anticoagulation.

PMID- 22988412
TI  - Septic thrombophlebitis in a HIV-positive intravenous drug user.
AB  - Septic thrombophlebitis of the pelvic veins may occur secondary to non-sterile
      intravenous drug injection and represents an uncommon yet life-threatening
      condition, most usually manifesting with persistent spiking fever and limb edema.
      Risk is further increased in HIV-infected people. High clinical suspicion and
      prompt imaging assessment with contrast-enhanced multidetector CT are necessary
      for correct diagnosis and staging, since early treatment prevents further
      complications such as systemic embolization.

PMID- 22988413
TI  - Gastric lavage in hair dye (Super-Vasmaol 33) poisoning: A friend or foe.

PMID- 22988414
TI  - Perinatal education and grandparenting: creating an interdependent family
      environment. Part I: documenting the need.
AB  - This is the first of two articles on the development, implementation, and
      evaluation of a grandparenting perinatal education program. In part one, a review
      of the literature is presented, along with the planned content and objectives for
      the program.

PMID- 22988415
TI  - Looking back in time: an interview with madame blanche cohen.
AB  - Madame Blanche Cohen, a French physiotherapist, was both a colleague of Drs.
      Fernand Lamaze and Pierre Vellay and their primary teacher of the Lamaze method
      (also known as accouchement sans douleur, or "painless childbirth"). She is the
      woman we read about in Marjorie Karmel's landmark book, Thank You, Dr. Lamaze. In
      her Paris apartment in 1955, Madame Cohen conducted private classes to prepare
      Marjorie for her birth experience. She also served as Marjorie's monitrice when
      Marjorie gave birth to her first daughter. Madame Cohen is still living in France
      with her husband, Henry. In this interview, she shares a fascinating glimpse into
      the history of the Lamaze method.

PMID- 22988416
TI  - Sex and babies: pregnant couples' postnatal sexual concerns.
AB  - What are pregnant couples' concerns regarding their sexual relationship after
      their baby's arrival? A study in regard to this question was conducted with five
      prenatal groups (n = 82). Its results are presented in this article. The sexual
      concerns are categorized as being about physical matters, psychological issues,
      adaptation issues, and anticipatory planning. A review of the literature then
      develops the theoretical interpretation of each of the sexual concerns and offers
      suggestions for childbirth educators to address some of these issues.

PMID- 22988417
TI  - Analysis and application of the concept of modesty to breastfeeding.
AB  - Modesty may be a significant variable impacting breast- feeding outcomes in
      western cultures, yet this term has received minimal attention in the
      breastfeeding literature. An analysis of the concept of modesty was conducted to
      gain greater understanding of the potential impact of modesty on breastfeeding
      outcomes. Various uses of the term modesty and particularly modesty in the
      context of breastfeeding are discussed in this paper. The defining attributes of
      breastfeeding modesty are identified and examples are provided. Implications for
      research and clinical practice are suggested.

PMID- 22988418
TI  - Professional nursing may include teaching childbirth classes.
AB  - In answer to a reader's question, this column advises licensed nurses who are
      also Lamaze certified childbirth educators that teaching childbirth classes is
      indeed considered within the scope of the practice of nursing.

PMID- 22988419
TI  - Once upon a time . . .
AB  - Telling stories to help relieve a woman in labor may be soothing, but one must be
      sure to choose the right tale.

PMID- 22988420
TI  - Leaving a lamaze legacy.
AB  - The author reaches out across the years to establish a new link with Madame
      Blanche Cohen and acknowledge her legacy in ongoing efforts to promote natural
      childbirth.

PMID- 22988421
TI  - Trichomoniasis and lactoferrin: future prospects.
AB  - Trichomonas vaginalis is a parasitic protozoan which infects the urogenital tract
      and requires iron as an essential nutrient. Iron is known to upregulate various
      adhesins required for cytoadherance and other factors involved in pathogenesis.
      At mucosal surfaces, iron is chelated by lactoferrin resulting in low levels of
      free iron. However, pathogens have evolved mechanisms for an increased uptake of
      iron. The present review highlights the role of iron in survival of Trichomonas
      during fluctuating concentrations of iron at mucosal surfaces during the
      menstrual cycle. Future prospects in terms of new drug and vaccine targets
      related to iron and its receptors have also been described.

PMID- 22988424
TI  - Biometrics and biosecurity.

PMID- 22988422
TI  - The immunologic injury composite with balloon injury leads to dyslipidemia: a
      robust rabbit model of human atherosclerosis and vulnerable plaque.
AB  - Atherosclerosis is a condition in which a lipid deposition, thrombus formation,
      immune cell infiltration, and a chronic inflammatory response, but its systemic
      study has been hampered by the lack of suitable animal models, especially in
      herbalism fields. We have tried to perform a perfect animal model that completely
      replicates the stages of human atherosclerosis. This is the first combined study
      about the immunologic injury and balloon injury based on the cholesterol diet. In
      this study, we developed a modified protocol of the white rabbit model that could
      represent a novel approach to studying human atherosclerosis and vulnerable
      plaque.

PMID- 22988423
TI  - Role of vitamin D in insulin resistance.
AB  - Vitamin D is characterized as a regulator of homeostasis of bone and mineral
      metabolism, but it can also provide nonskeletal actions because vitamin D
      receptors have been found in various tissues including the brain, prostate,
      breast, colon, pancreas, and immune cells. Bone metabolism, modulation of the
      immune response, and regulation of cell proliferation and differentiation are all
      biological functions of vitamin D. Vitamin D may play an important role in
      modifying the risk of cardiometabolic outcomes, including diabetes mellitus (DM),
      hypertension, and cardiovascular disease. The incidence of type 2 DM is
      increasing worldwide and results from a lack of insulin or inadequate insulin
      secretion following increases in insulin resistance. Therefore, it has been
      proposed that vitamin D deficiency plays an important role in insulin resistance
      resulting in diabetes. The potential role of vitamin D deficiency in insulin
      resistance has been proposed to be associated with inherited gene polymorphisms
      including vitamin D-binding protein, vitamin D receptor, and vitamin D 1 alpha
      hydroxylase gene. Other roles have been proposed to involve immunoregulatory
      function by activating innate and adaptive immunity and cytokine release,
      activating inflammation by upregulation of nuclear factor kappaB and inducing
      tumor necrosis factor alpha, and other molecular actions to maintain glucose
      homeostasis and mediate insulin sensitivity by a low calcium status, obesity, or
      by elevating serum levels of parathyroid hormone. These effects of vitamin D
      deficiency, either acting in concert or alone, all serve to increase insulin
      resistance. Although there is evidence to support a relationship between vitamin
      D status and insulin resistance, the underlying mechanism requires further
      exploration. The purpose of this paper was to review the current information
      available concerning the role of vitamin D in insulin resistance.

PMID- 22988425
TI  - Pigment epithelium-derived factor: chemistry, structure, biology, and
      applications.

PMID- 22988426
TI  - Mercury toxicity.

PMID- 22988428
TI  - Dependability modeling and assessment in UML-based software development.
AB  - Assessment of software nonfunctional properties (NFP) is an important problem in
      software development. In the context of model-driven development, an emerging
      approach for the analysis of different NFPs consists of the following steps: (a)
      to extend the software models with annotations describing the NFP of interest;
      (b) to transform automatically the annotated software model to the formalism
      chosen for NFP analysis; (c) to analyze the formal model using existing solvers;
      (d) to assess the software based on the results and give feedback to designers.
      Such a modeling->analysis->assessment approach can be applied to any software
      modeling language, be it general purpose or domain specific. In this paper, we
      focus on UML-based development and on the dependability NFP, which encompasses
      reliability, availability, safety, integrity, and maintainability. The paper
      presents the profile used to extend UML with dependability information, the model
      transformation to generate a DSPN formal model, and the assessment of the system
      properties based on the DSPN results.

PMID- 22988427
TI  - Sunflower oil supplementation has proinflammatory effects and does not reverse
      insulin resistance in obesity induced by high-fat diet in C57BL/6 mice.
AB  - High consumption of polyunsaturated fatty acids, such as sunflower oil has been
      associated to beneficial effects in plasma lipid profile, but its role on
      inflammation and insulin resistance is not fully elucidated yet. We evaluated the
      effect of sunflower oil supplementation on inflammatory state and insulin
      resistance condition in HFD-induced obese mice. C57BL/6 male mice (8 weeks) were
      divided in four groups: (a) control diet (CD), (b) HFD, (c) CD supplemented with
      n-6 (CD + n-6), and (d) HFD supplemented with n-6 (HFD + n-6). CD + n-6 and HFD +
      n-6 were supplemented with sunflower oil by oral gavage at 2 g/Kg of body weight,
      three times per week. CD and HFD were supplemented with water instead at the same
      dose. HFD induced whole and muscle-specific insulin resistance associated with
      increased inflammatory markers in insulin-sensitive tissues and macrophage cells.
      Sunflower oil supplementation was not efficient in preventing or reducing these
      parameters. In addition, the supplementation increased pro-inflammatory cytokine
      production by macrophages and tissues. Lipid profile, on the other hand, was
      improved with the sunflower oil supplementation in animals fed HFD. In
      conclusion, sunflower oil supplementation improves lipid profile, but it does not
      prevent or attenuate insulin resistance and inflammation induced by HFD in
      C57BL/6 mice.

PMID- 22988429
TI  - Development of Chinese adolescents: assessment, issues, and intervention.

PMID- 22988431
TI  - Activity of protease-activated receptors in primary cultured human myenteric
      neurons.
AB  - Activity of the four known protease-activated receptors (PARs) has been well
      studied in rodent enteric nervous system and results in animal models established
      an important role for neuronal PAR2. We recently demonstrated that, unlike in
      rodents, PAR1 is the dominant neuronal protease receptor in the human submucous
      plexus. With this study we investigated whether this also applies to the human
      myenteric plexus. We used voltage sensitive dye recordings to detect action
      potential discharge in primary cultures of human myenteric neurons in response to
      PAR activating peptides (APs). Application of the PAR1-AP (TFLLR) or PAR4-AP
      (GYPGQV) evoked spike discharge in 79 or 23% of myenteric neurons, respectively.
      The PAR1-AP response was mimicked by the endogenous PAR1 activator thrombin and
      blocked by the PAR1 antagonists SCH79797. Human myenteric neurons did not respond
      to PAR2-AP. This was not due to culture conditions because all three PAR-APs
      evoked action potentials in cultured guinea pig myenteric neurons. Consecutive
      application of PAR-APs revealed coexpression (relative to the population
      responding to PAR-APs) of PAR1/PAR2 in 51%, PAR1/PAR4 in 43%, and of PAR2/PAR4 in
      29% of guinea pig myenteric neurons. Our study provided further evidence for the
      prominent role of neuronal PAR1 in the human enteric nervous system.

PMID- 22988430
TI  - A genome-wide screen to identify transcription factors expressed in pelvic
      Ganglia of the lower urinary tract.
AB  - Relative positions of neurons within mature murine pelvic ganglia based on
      expression of neurotransmitters have been described. However the spatial
      organization of developing innervation in the murine urogenital tract (UGT) and
      the gene networks that regulate specification and maturation of neurons within
      the pelvic ganglia of the lower urinary tract (LUT) are unknown. We used whole
      mount immunohistochemistry and histochemical stains to localize neural elements
      in 15.5 days post coitus (dpc) fetal mice. To identify potential regulatory
      factors expressed in pelvic ganglia, we surveyed expression patterns for known or
      probable transcription factors (TF) annotated in the mouse genome by screening a
      whole-mount in situ hybridization library of fetal UGTs. Of the 155 genes
      detected in pelvic ganglia, 88 encode TFs based on the presence of predicted DNA
      binding domains. Neural crest (NC)-derived progenitors within the LUT were
      labeled by Sox10, a well-known regulator of NC development. Genes identified were
      categorized based on patterns of restricted expression in pelvic ganglia, pelvic
      ganglia and urethral epithelium, or pelvic ganglia and urethral mesenchyme. Gene
      expression patterns and the distribution of Sox10+, Phox2b+, Hu+, and PGP9.5+
      cells within developing ganglia suggest previously unrecognized regional
      segregation of Sox10+ progenitors and differentiating neurons in early
      development of pelvic ganglia. Reverse transcription-PCR of pelvic ganglia RNA
      from fetal and post-natal stages demonstrated that multiple TFs maintain post
      natal expression, although Pax3 is extinguished before weaning. Our analysis
      identifies multiple potential regulatory genes including TFs that may participate
      in segregation of discrete lineages within pelvic ganglia. The genes identified
      here are attractive candidate disease genes that may now be further investigated
      for their roles in malformation syndromes or in LUT dysfunction.

PMID- 22988432
TI  - Entorhinal theta-frequency input to the dentate gyrus trisynaptically evokes
      hippocampal CA1 LTP.
AB  - There exists substantial evidence that some forms of explicit learning in mammals
      require long-term potentiation (LTP) at hippocampal CA3-CA1 synapses. While CA1
      LTP has been well characterized at the monosynaptic level, it still remains
      unclear how the afferent systems to the hippocampus can initiate formation of
      this neuroplastic phenomenon. Using voltage-sensitive dye imaging (VSDI) in a
      mouse brain slice preparation, we show that evoked entorhinal cortical (EC) theta
      frequency input to the dentate gyrus highly effectively generates waves of
      neuronal activity which propagate through the entire trisynaptic circuit of the
      hippocampus ("HTC-Waves"). This flow of activity, which we also demonstrate in
      vivo, critically depends on frequency facilitation of mossy fiber to CA3 synaptic
      transmission. The HTC-Waves are rapidly boosted by the cognitive enhancer
      caffeine (5 MUM) and the stress hormone corticosterone (100 nM). They precisely
      follow the rhythm of the EC input, involve high-frequency firing (>100 Hz) of CA3
      pyramidal neurons, and induce NMDA receptor-dependent CA1 LTP within a few
      seconds. Our study provides the first experimental evidence that synchronous
      theta-rhythmical spiking of EC stellate cells, as occurring during EC theta
      oscillations, has the capacity to drive induction of CA1 LTP via the hippocampal
      trisynaptic pathway. Moreover, we present data pointing to a basic filter
      mechanism of the hippocampus regarding EC inputs and describe a methodology to
      reveal alterations in the "input-output relationship" of the hippocampal
      trisynaptic circuit.

PMID- 22988433
TI  - Automated measurement of the human corpus callosum using MRI.
AB  - The corpus callosum includes the majority of fibers that connect the two cortical
      hemispheres. Studies of cross-sectional callosal morphometry and area have
      revealed developmental, gender, and hemispheric differences in healthy
      populations and callosal deficits associated with neurodegenerative disease and
      brain injury. However, accurate quantification of the callosum using magnetic
      resonance imaging is complicated by intersubject variability in callosal size,
      shape, and location and often requires manual outlining of the callosum in order
      to achieve adequate performance. Here we describe an objective, fully automated
      protocol that utilizes voxel-based images to quantify the area and thickness both
      of the entire callosum and of different callosal compartments. We verify the
      method's accuracy, reliability, robustness, and multisite consistency and make
      comparisons with manual measurements using public brain-image databases. An
      analysis of age-related changes in the callosum showed increases in length and
      reductions in thickness and area with age. A comparison of older subjects with
      and without mild dementia revealed that reductions in anterior callosal area
      independently predicted poorer cognitive performance after factoring out Mini
      Mental Status Examination scores and normalized whole brain volume. Open-source
      software implementing the algorithm is available at www.nitrc.org/projects/c8c8.

PMID- 22988434
TI  - Challenges and opportunities for characterizing cognitive aging across species.
AB  - The gradual decline of cognitive ability with age, even in the absence of overt
      brain disease, is a growing problem. Although cognitive aging is a common and
      feared accompaniment of the aging process, its underlying mechanisms are not well
      understood and there are no highly effective means to prevent it. Additional
      research on cognitive aging is sorely needed, and methods that enable ready
      translation between human subjects and animal models stand to provide the most
      benefit. Here and in the six companion pieces in this special issue, we discuss a
      variety of challenges and opportunities for studying cognitive aging across
      species. We identify tests of associative memory, recognition memory, spatial and
      contextual memory, and working memory and executive function as cognitive domains
      that are age-sensitive and amenable to testing with parallel means in both humans
      and animal models. We summarize some of the important challenges in using animal
      models to test cognition. We describe unique opportunities to study cognitive
      aging in human subjects, such as those provided by recent large-scale initiatives
      to characterize cognition in large groups of subjects across the lifespan.
      Finally, we highlight some of the challenges of studying cognitive aging in human
      subjects.

PMID- 22988435
TI  - Characterizing cognitive aging of associative memory in animal models.
AB  - An overview is provided of the simple single-cue delay and trace eyeblink
      conditioning paradigms as techniques to assess associative learning and memory in
      the aged. We highlight and focus this review on the optimization of the parameter
      space of eyeblink conditioning designs in the aged to avoid and control for
      potential confounds that may arise when studying aged mammals. The need to
      examine the contribution of non-associative factors that can contribute to
      performance outcomes is emphasized, and how age-related changes in the central
      nervous system as well as peripheral sensory factors can potentially bias the
      interpretation of the data in the aged is discussed. The way in which slight
      alterations of the parameter space in the delay and trace eyeblink conditioning
      paradigms can lead to delayed but intact conditioning, rather than impaired
      performance in aged animals is also discussed. Overall, the eyeblink conditioning
      paradigm, when optimized for the age of the animal in the study, is an elegantly
      simple technique for assessment of associative learning and memory. When design
      caveats described above are taken into account, this important type of memory,
      with its well-defined neural substrates, should definitely be included in
      cognitive assessment batteries for the aged.

PMID- 22988437
TI  - Characterizing cognitive aging of recognition memory and related processes in
      animal models and in humans.
AB  - Analyses of complex behaviors across the lifespan of animals can reveal the brain
      regions that are impacted by the normal aging process, thereby, elucidating
      potential therapeutic targets. Recent data from rats, monkeys, and humans
      converge, all indicating that recognition memory and complex visual perception
      are impaired in advanced age. These cognitive processes are also disrupted in
      animals with lesions of the perirhinal cortex, indicating that the the functional
      integrity of this structure is disrupted in old age. This current review
      summarizes these data, and highlights current methodologies for assessing
      perirhinal cortex-dependent behaviors across the lifespan.

PMID- 22988438
TI  - Characterizing cognitive aging of working memory and executive function in animal
      models.
AB  - Executive functions supported by prefrontal cortical (PFC) systems provide
      essential control and planning mechanisms to guide goal-directed behavior. As
      such, age-related alterations in executive functions can mediate profound and
      widespread deficits on a diverse array of neurocognitive processes. Many of the
      critical neuroanatomical and functional characteristics of prefrontal cortex are
      preserved in rodents, allowing for meaningful cross species comparisons relevant
      to the study of cognitive aging. In particular, as rodents lend themselves to
      genetic, cellular and biochemical approaches, rodent models of executive function
      stand to significantly contribute to our understanding of the critical
      neurobiological mechanisms that mediate decline of executive processes across the
      lifespan. Moreover, rodent analogs of executive functions that decline in human
      aging represent an essential component of a targeted, rational approach for
      developing and testing effective treatment and prevention therapies for age
      related cognitive decline. This paper reviews behavioral approaches used to study
      executive function in rodents, with a focus on those assays that share a
      foundation in the psychological and neuroanatomical constructs important for
      human aging. A particular emphasis is placed on behavioral approaches used to
      assess working memory and cognitive flexibility, which are sensitive to decline
      with age across species and for which strong rodent models currently exist. In
      addition, other approaches in rodent behavior that have potential for providing
      analogs to functions that reliably decline to human aging (e.g., information
      processing speed) are discussed.

PMID- 22988436
TI  - Characterizing cognitive aging of spatial and contextual memory in animal models.
AB  - Episodic memory, especially memory for contextual or spatial information, is
      particularly vulnerable to age-related decline in humans and animal models of
      aging. The continuing improvement of virtual environment technology for testing
      humans signifies that widely used procedures employed in the animal literature
      for examining spatial memory could be developed for examining age-related
      cognitive decline in humans. The current review examines cross species
      considerations for implementing these tasks and translating findings across
      different levels of analysis. The specificity of brain systems as well as gaps in
      linking human and animal laboratory models is discussed.

PMID- 22988440
TI  - Characterizing healthy samples for studies of human cognitive aging.
AB  - Characterizing the cognitive declines associated with aging, and differentiating
      them from the effects of disease in older adults, are important goals for human
      neuroscience researchers. This is also an issue of public health urgency in
      countries with rapidly aging populations. Progress toward understanding cognitive
      aging is complicated by numerous factors. Researchers interested in cognitive
      changes in healthy older adults need to consider these complexities when they
      design and interpret studies. This paper addresses important factors in study
      design, patient demographics, co-morbid and incipient medical conditions, and
      assessment instruments that will allow researchers to optimize the
      characterization of healthy participants and produce meaningful and generalizable
      research outcomes from studies of cognitive aging. Application of knowledge from
      well-designed studies should be useful in clinical settings to facilitate the
      earliest possible recognition of disease and guide appropriate interventions to
      best meet the needs of the affected individual and public health priorities.

PMID- 22988439
TI  - Characterizing cognitive aging in humans with links to animal models.
AB  - With the population of older adults expected to grow rapidly over the next two
      decades, it has become increasingly important to advance research efforts to
      elucidate the mechanisms associated with cognitive aging, with the ultimate goal
      of developing effective interventions and prevention therapies. Although there
      has been a vast research literature on the use of cognitive tests to evaluate the
      effects of aging and age-related neurodegenerative disease, the need for a set of
      standardized measures to characterize the cognitive profiles specific to healthy
      aging has been widely recognized. Here we present a review of selected methods
      and approaches that have been applied in human research studies to evaluate the
      effects of aging on cognition, including executive function, memory, processing
      speed, language, and visuospatial function. The effects of healthy aging on each
      of these cognitive domains are discussed with examples from
      cognitive/experimental and clinical/neuropsychological approaches. Further, we
      consider those measures that have clear conceptual and methodological links to
      tasks currently in use for non-human animal studies of aging, as well as those
      that have the potential for translation to animal aging research. Having a
      complementary set of measures to assess the cognitive profiles of healthy aging
      across species provides a unique opportunity to enhance research efforts for
      cross-sectional, longitudinal, and intervention studies of cognitive aging.
      Taking a cross-species, translational approach will help to advance cognitive
      aging research, leading to a greater understanding of associated neurobiological
      mechanisms with the potential for developing effective interventions and
      prevention therapies for age-related cognitive decline.

PMID- 22988441
TI  - Decreasing Poly(ADP-Ribose) Polymerase Activity Restores DeltaF508 CFTR
      Trafficking.
AB  - Most cystic fibrosis is caused by mutations in CFTR that prevent its trafficking
      from the ER to the plasma membrane and is associated with exaggerated
      inflammation, altered metabolism, and diminished responses to oxidative stress.
      PARP-1 is activated by oxidative stress and causes energy depletion and cell
      dysfunction. Inhibition of this enzyme protects against excessive inflammation
      and recent studies have also implicated it in intracellular protein trafficking.
      We hypothesized that PARP-1 activity is altered in CF and affects trafficking and
      function of the most common CF mutant DeltaF508 CFTR. Indeed, PARP-1 activity was
      2.9-fold higher in CF (DeltaF508/DeltaF508) human bronchial epithelial primary
      cells than in non-CF cells, and similar results were obtained by comparing CF vs.
      non-CF bronchial epithelial cell lines (2.5-fold higher in CFBE41o(-) vs.
      16HBE14o(-), P < 0.002). A PARP-1 inhibitor (ABT-888, Veliparib) partially
      restored CFTR channel activity in CFBE41o(-) cells overexpressing DeltaF508 CFTR.
      Similarly, reducing PARP-1 activity by 85% in ileum from transgenic CF mice
      (Cftr(tm1)Eur) partially rescued DeltaF508 CFTR activity to 7% of wild type mouse
      levels, and similar correction (7.8%) was observed in vivo by measuring salivary
      secretion. Inhibiting PARP-1 with ABT-888 or siRNA partially restored DeltaF508
      CFTR trafficking in cell lines, and most DeltaF508 CFTR was complex glycosylated
      when heterologously expressed in PARP-1(-/-) mouse embryonic fibroblasts.
      Finally, levels of the mature glycoform of CFTR were reduced by peroxynitrite, a
      strong activator of PARP-1. These results demonstrate that PARP-1 activity is
      increased in CF, and identify a novel pathway that could be targeted by
      proteostatic correctors of CFTR trafficking.

PMID- 22988444
TI  - Lipid binding proteins from parasitic platyhelminthes.
AB  - TWO MAIN FAMILIES OF LIPID BINDING PROTEINS HAVE BEEN IDENTIFIED IN PARASITIC
      PLATYHELMINTHES: hydrophobic ligand binding proteins (HLBPs) and fatty acid
      binding proteins (FABPs). Members of the former family of proteins are specific
      to the Cestoda class, while FABPs are conserved across a wide range of animal
      species. Because Platyhelminthes are unable to synthesize their own lipids, these
      lipid-binding proteins are important molecules in these organisms. HLBPs are a
      high molecular mass complex of proteins and lipids. They are composed of subunits
      of low molecular mass proteins and a wide array of lipid molecules ranging from
      CoA esters to cholesterol. These proteins are excretory-secretory molecules and
      are key serological tools for diagnosis of diseases caused by cestodes. FABPs are
      mainly intracellular proteins of low molecular weight. They are also vaccine
      candidates. Despite that the knowledge of their function is scarce, the
      differences in their molecular organization, ligand preferences,
      intra/extracellular localization, evolution, and phylogenetic distribution,
      suggest that platyhelminths HLBPs and FABPs should play different functions.
      FABPs might be involved in the removal of fatty acids from the inner surface of
      the cell membrane and in their subsequent targeting to specific cellular
      destinations. In contrast, HLBPs might be involved in fatty acid uptake from the
      host environment.

PMID- 22988445
TI  - Lack of Association of ACE2 G8790A Gene Mutation with Essential Hypertension in
      the Chinese Population: A Meta-Analysis Involving 5260 Subjects.
AB  - BACKGROUND: The angiotensin converting enzyme 2 (ACE2) G8790A gene polymorphism
      has been associated with the susceptibility to essential hypertension (EH), but
      the results are disputable. OBJECTIVE AND METHODS: To investigate the
      relationship between the ACE2 G8790A gene polymorphism and EH, eight separate
      studies with 5260 subjects were meta-analyzed. The pooled odds ratio (OR) and its
      corresponding 95% confidence interval (CI) were calculated by a random effect
      model. RESULTS: In the ACE2 G8790A gene polymorphism and EH meta-analysis in a
      Chinese population, no significant association was found between the ACE2 G8790A
      gene polymorphism and EH (OR: 1.03, 95% CI: 0.87-1.21, P = 0.76). In the
      stratified analysis by gender, no significant risk was found among males (OR:
      1.06, 95% CI: 0.82-1.36, P = 0.66) or females (OR: 0.98, 95% CI: 0.77-1.24, P =
      0.85). Under a dominant model of inheritance in the female subgroup, the pooled
      OR for the GG/GA + AA value was 1.01 (95% CI: 0.82-1.25, P = 0.92). Under a
      recessive model of inheritance in the female subgroup, the pooled OR for the
      AA/AG + GG value was 0.93 (95% CI: 0.50-1.73, P = 0.83). CONCLUSION: The current
      meta-analysis suggested that the ACE2 G8790A gene polymorphism might not be
      related to the increased EH risk in the Chinese population.

PMID- 22988442
TI  - Mechanism of electromechanical coupling in voltage-gated potassium channels.
AB  - Voltage-gated ion channels play a central role in the generation of action
      potentials in the nervous system. They are selective for one type of ion -
      sodium, calcium, or potassium. Voltage-gated ion channels are composed of a
      central pore that allows ions to pass through the membrane and four peripheral
      voltage sensing domains that respond to changes in the membrane potential. Upon
      depolarization, voltage sensors in voltage-gated potassium channels (Kv) undergo
      conformational changes driven by positive charges in the S4 segment and aided by
      pairwise electrostatic interactions with the surrounding voltage sensor.
      Structure-function relations of Kv channels have been investigated in detail, and
      the resulting models on the movement of the voltage sensors now converge to a
      consensus; the S4 segment undergoes a combined movement of rotation, tilt, and
      vertical displacement in order to bring 3-4e(+) each through the electric field
      focused in this region. Nevertheless, the mechanism by which the voltage sensor
      movement leads to pore opening, the electromechanical coupling, is still not
      fully understood. Thus, recently, electromechanical coupling in different Kv
      channels has been investigated with a multitude of techniques including
      electrophysiology, 3D crystal structures, fluorescence spectroscopy, and
      molecular dynamics simulations. Evidently, the S4-S5 linker, the covalent link
      between the voltage sensor and pore, plays a crucial role. The linker transfers
      the energy from the voltage sensor movement to the pore domain via an interaction
      with the S6 C-termini, which are pulled open during gating. In addition, other
      contact regions have been proposed. This review aims to provide (i) an in-depth
      comparison of the molecular mechanisms of electromechanical coupling in different
      Kv channels; (ii) insight as to how the voltage sensor and pore domain influence
      one another; and (iii) theoretical predictions on the movement of the cytosolic
      face of the Kv channels during gating.

PMID- 22988446
TI  - Transcranial direct current stimulation modulates human color discrimination in a
      pathway-specific manner.
AB  - Previous research showed that transcranial direct current stimulation (tDCS) can
      modulate visual cortex excitability. However, there is no experiment on the
      effects of tDCS on color perception to date. The present study aimed to
      investigate the effects of tDCS on color discrimination tasks. Fifteen healthy
      subjects (mean age of 25.6 +/- 4.4 years) were tested with Cambridge Color Test
      2.0 (Trivector and ellipses protocols) and a Forced-choice Spatial Color Contrast
      Sensitivity task (vertical red-green sinusoidal grating) while receiving tDCS.
      Anodal, cathodal, and sham tDCS were delivered at Oz for 22 min using two square
      electrodes (25 cm(2) with a current of 1.5 mA) in sessions separated by 7 days.
      Anodal tDCS significantly increased tritan sensitivity (p < 0.01) and had no
      significant effect on protan, deutan, or red-green grating discrimination. The
      effects on the tritan discrimination returned to baseline after 15 min (p <
      0.01). Cathodal tDCS reduced the sensitivity in the deutan axis and increased
      sensitivity in the tritan axis (p < 0.05). The lack of anodal tDCS effects in the
      protan, deutan, and red-green grating sensitivities could be explained by a
      "ceiling effect" since adults in this age range tend to have optimal color
      discrimination performance for these hues. The differential effects of cathodal
      tDCS on tritan and deutan sensitivities and the absence of the proposed ceiling
      effects for the tritan axes might be explained by Parvocellular (P) and
      Koniocellular (K) systems with regard to their functional, physiological, and
      anatomical differences. The results also support the existence of a systematic
      segregation of P and K color-coding cells in V1. Future research and possible
      clinical implications are discussed.

PMID- 22988447
TI  - Systems biology of microbial infection.

PMID- 22988443
TI  - Cancer cell growth and survival as a system-level property sustained by enhanced
      glycolysis and mitochondrial metabolic remodeling.
AB  - Systems Biology holds that complex cellular functions are generated as system
      level properties endowed with robustness, each involving large networks of
      molecular determinants, generally identified by "omics" analyses. In this paper
      we describe four basic cancer cell properties that can easily be investigated in
      vitro: enhanced proliferation, evasion from apoptosis, genomic instability, and
      inability to undergo oncogene-induced senescence. Focusing our analysis on a K
      ras dependent transformation system, we show that enhanced proliferation and
      evasion from apoptosis are closely linked, and present findings that indicate how
      a large metabolic remodeling sustains the enhanced growth ability. Network
      analysis of transcriptional profiling gives the first indication on this
      remodeling, further supported by biochemical investigations and metabolic flux
      analysis (MFA). Enhanced glycolysis, down-regulation of TCA cycle, decoupling of
      glucose and glutamine utilization, with increased reductive carboxylation of
      glutamine, so to yield a sustained production of growth building blocks and
      glutathione, are the hallmarks of enhanced proliferation. Low glucose
      availability specifically induces cell death in K-ras transformed cells, while
      PKA activation reverts this effect, possibly through at least two mitochondrial
      targets. The central role of mitochondria in determining the two investigated
      cancer cell properties is finally discussed. Taken together the findings reported
      herein indicate that a system-level property is sustained by a cascade of
      interconnected biochemical pathways that behave differently in normal and in
      transformed cells.

PMID- 22988448
TI  - Podoplanin: emerging functions in development, the immune system, and cancer.
AB  - Podoplanin (PDPN) is a well-conserved, mucin-type transmembrane protein expressed
      in multiple tissues during ontogeny and in adult animals, including the brain,
      heart, kidney, lungs, osteoblasts, and lymphoid organs. Studies of PDPN-deficient
      mice have demonstrated that this molecule plays a critical role in development of
      the heart, lungs, and lymphatic system. PDPN is widely used as a marker for
      lymphatic endothelial cells and fibroblastic reticular cells of lymphoid organs
      and for lymphatics in the skin and tumor microenvironment. Much of the
      mechanistic insight into PDPN biology has been gleaned from studies of tumor
      cells; tumor cells often upregulate PDPN as they undergo epithelial-mesenchymal
      transition and this upregulation is correlated with increased motility and
      metastasis. The physiological role of PDPN that has been most studied is its
      ability to aggregate and activate CLEC-2-expressing platelets, as PDPN is the
      only known endogenous ligand for CLEC-2. However, more recent studies have
      revealed that PDPN also plays crucial roles in the biology of immune cells,
      including T cells and dendritic cells. This review will provide a comprehensive
      overview of the diverse roles of PDPN in development, immunology, and cancer.

PMID- 22988449
TI  - The non-coding oncogene: a case of missing DNA evidence?
AB  - The evidence that links classical protein-coding proto-oncogenes and tumor
      suppressors, such as MYC, RAS, P53, and RB, to carcinogenesis is indisputable.
      Multiple lines of proof show how random somatic genomic alteration of such genes
      (e.g., mutation, deletion, or amplification), followed by selection and clonal
      expansion, forms the main molecular basis of tumor development. Many important
      cancer genes were discovered using low-throughput approaches in the pre-genomic
      era, and this knowledge is today solidified and expanded upon by modern genome
      scale methodologies. In several recent studies, non-coding RNAs (ncRNAs), such as
      microRNAs and long ncRNAs (lncRNAs), have been shown to contribute to tumor
      development. However, in comparison with coding cancer genes, the genomic (DNA
      level) evidence is sparse for ncRNAs. The coding proto-oncogenes and tumor
      suppressors that we know of today are major molecular hubs in both normal and
      malignant cells. The search for ncRNAs with tumor driver or suppressor roles
      therefore holds the additional promise of pinpointing important, biologically
      active, ncRNAs in a vast and largely uncharacterized non-coding transcriptome.
      Here, we assess the available DNA-level data that links non-coding genes to tumor
      development. We further consider historical, methodological, and biological
      aspects, and discuss future prospects of ncRNAs in cancer.

PMID- 22988450
TI  - Diverse developmental disorders from the one ring: distinct molecular pathways
      underlie the cohesinopathies.
AB  - The multi-subunit protein complex, cohesin, is responsible for sister chromatid
      cohesion during cell division. The interaction of cohesin with DNA is controlled
      by a number of additional regulatory proteins. Mutations in cohesin, or its
      regulators, cause a spectrum of human developmental syndromes known as the
      "cohesinopathies." Cohesinopathy disorders include Cornelia de Lange Syndrome and
      Roberts Syndrome. The discovery of novel roles for chromatid cohesion proteins in
      regulating gene expression led to the idea that cohesinopathies are caused by
      dysregulation of multiple genes downstream of mutations in cohesion proteins.
      Consistent with this idea, Drosophila, mouse, and zebrafish cohesinopathy models
      all show altered expression of developmental genes. However, there appears to be
      incomplete overlap among dysregulated genes downstream of mutations in different
      components of the cohesion apparatus. This is surprising because mutations in all
      cohesion proteins would be predicted to affect cohesin's roles in cell division
      and gene expression in similar ways. Here we review the differences and
      similarities between genetic pathways downstream of components of the cohesion
      apparatus, and discuss how such differences might arise, and contribute to the
      spectrum of cohesinopathy disorders. We propose that mutations in different
      elements of the cohesion apparatus have distinct developmental outcomes that can
      be explained by sometimes subtly different molecular effects.

PMID- 22988451
TI  - Propyl gallate plays a nephroprotective role in early stage of diabetic
      nephropathy associated with suppression of glomerular endothelial cell
      proliferation and angiogenesis.
AB  - There is growing evidence suggesting that glomerular endothelial cell
      proliferation and angiogenesis may be responsible for the pathophysiological
      events in the early stage of diabetic nephropathy. This study was designed to
      investigate the factors related to glomerular endothelial cell proliferation and
      glomerular angiogenesis and assess the effect of propyl gallate on preventing
      these disorders in diabetic rats. We found that glomerular hypertrophy,
      glomerular mesangial matrix expansion, and albuminuria were significantly
      increased in DN rats. CD31+ endothelial cells significantly increased in
      glomerulus of diabetic rats. Double immunofluorescence staining showed some
      structurally defective vasculus tubes in glomerulus. Real-time PCR and western
      blot demonstrated the glomerular eNOS expression remained at the same level,
      while remarkable decreased NO productions and suppressed eNOS activities were
      observed in diabetic rats. Treatment with propyl gallate improved glomerular
      pathological changes, reduced endothelial cell proliferation, decreased
      albuminuria, and restored eNOS activity, but did not alter eNOS expression. These
      data suggest that endothelial cell proliferation and immature angiogenesis may be
      the contributors to progression of DN. Propyl gallate is a potential novel
      therapeutic agent on prevention of diabetic nephropathy.

PMID- 22988453
TI  - Celiac artery compression syndrome: an experience in a single institution in
      taiwan.
AB  - Celiac artery compression syndrome (CACS) or median arcuate ligament (MAL)
      syndrome is a rare vascular disease. The clinical manifestations of CACS include
      the triad of postprandial pain, vomiting, and weight loss. The pathogenesis of
      CACS is the external compression of celiac artery by the MAL or celiac ganglion.
      Moreover, some authors also reported the compression with different etiologies,
      such as neoplasms of pancreatic head, adjacent duodenal carcinoma, vascular
      aneurysms, aortic dissection, or sarcoidosis. In the literature, most cases of
      CACS were reported from Western countries. In contrast, this disease was seldom
      reported in Oriental countries or regions, including Taiwan. Superior mesenteric
      artery syndrome (SMAS) is also a rare disease characterized by compression of the
      third portion of the duodenum by the SMA. The clinical features of SMAS are
      postprandial pain, vomiting, and weight loss. To date, there are no guidelines to
      ensure the proper treatment of patients with CACS because of its low incidence.
      Thus, tailored therapy for patients with CACS remains a challenge as well as the
      prediction of clinical response and prognosis. The aim of our present study was
      to investigate the clinical features, the association with SMAS, treatments, and
      outcomes of patients with CACS in a single institution in Taiwan.

PMID- 22988452
TI  - The infant skin barrier: can we preserve, protect, and enhance the barrier?
AB  - Infant skin is different from adult in structure, function, and composition.
      Despite these differences, the skin barrier is competent at birth in healthy,
      full-term neonates. The primary focus of this paper is on the developing skin
      barrier in healthy, full-term neonates and infants. Additionally, a brief
      discussion of the properties of the skin barrier in premature neonates and
      infants with abnormal skin conditions (i.e., atopic dermatitis and eczema) is
      included. As infant skin continues to mature through the first years of life, it
      is important that skin care products (e.g., cleansers and emollients) are
      formulated appropriately. Ideally, products that are used on infants should not
      interfere with skin surface pH or perturb the skin barrier. For cleansers, this
      can be achieved by choosing the right type of surfactant, by blending
      surfactants, or by blending hydrophobically-modified polymers (HMPs) with
      surfactants to increase product mildness. Similarly, choosing the right type of
      oil for emollients is important. Unlike some vegetable oils, mineral oil is more
      stable and is not subject to oxidation and hydrolysis. Although emollients can
      improve the skin barrier, more studies are needed to determine the potential long
      term benefits of using emollients on healthy, full-term neonates and infants.

PMID- 22988454
TI  - Management of peptic ulcer bleeding in different case volume workplaces: results
      of a nationwide inquiry in hungary.
AB  - The aim of this study was to conduct a national survey to evaluate the recent
      endoscopic treatment and drug therapy of peptic ulcer bleeding (PUB) patients and
      to compare practices in high and low case volume Hungarian workplaces. A total of
      62 gastroenterology units participated in the six-month study. A total of 3033
      PUB cases and a mean of 8.15 +/- 3.9 PUB cases per month per unit were reported.
      In the 23 high case volume units (HCV), there was a mean of 12.9 +/- 5.4 PUB
      cases/month, whereas in the 39 low case volume units (LCV), a mean of 5.3 +/- 2.9
      PUB cases/month were treated during the study period. In HCV units, endoscopic
      therapies for Forrest Ia, Ib, and IIa ulcers were significantly more often used
      than in LCV units (86% versus 68%; P = 0.001). Among patients with stigmata of
      recent haemorrhage (Forrest I, II), bolus + continuous infusion PPI was given
      significantly more frequently in HCV than in LCV units (49.6% versus 33.2%; P =
      0.001). Mortality in HCV units was less than in LCV units (2.7% versus 4.3%; P =
      0.023). The penetration of evidence-based recommendations for PUB management is
      stronger in HCV units resulting lower mortality.

PMID- 22988456
TI  - Effect of head rotation on cerebral blood velocity in the prone position.
AB  - Background. The prone position is applied to facilitate surgery of the back and
      to improve oxygenation in the respirator-treated patient. In particular, with
      positive pressure ventilation the prone position reduces venous return to the
      heart and in turn cardiac output (CO) with consequences for cerebral blood flow.
      We tested in healthy subjects the hypothesis that rotating the head in the prone
      position reduces cerebral blood flow. Methods. Mean arterial blood pressure
      (MAP), stroke volume (SV), and CO were determined, together with the middle
      cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters
      bilaterally in 22 healthy subjects in the prone position with the head centered,
      respectively, rotated sideways, with and without positive pressure breathing (10
      cmH(2)O). Results. The prone position reduced SV (by 5.4 +/- 1.5%; P < 0.05) and
      CO (by 2.3 +/- 1.9 %), and slightly increased MAP (from 78 +/- 3 to 80 +/- 2
      mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged.
      Positive pressure breathing in the prone position increased MAP (by 3.6 +/- 0.8
      mmHg) but further reduced SV and CO (by 9.3 +/- 1.3 % and 7.2 +/- 2.4 % below
      baseline) while MCA V(mean) was maintained. The head-rotated prone position with
      positive pressure breathing augmented MAP further (87 +/- 2 mmHg) but not CO,
      narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 +/- 3.2 %).
      Conclusion. During positive pressure breathing the prone position with sideways
      rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone
      positioning with rotated head affects both CBF and cerebrovenous drainage
      indicating that optimal brain perfusion requires head centering.

PMID- 22988457
TI  - Leprosy: an overview of pathophysiology.
AB  - Leprosy, also known as Hansen's disease, is a chronic infectious disease caused
      by Mycobacterium leprae, a microorganism that has a predilection for the skin and
      nerves. The disease is clinically characterized by one or more of the three
      cardinal signs: hypopigmented or erythematous skin patches with definite loss of
      sensation, thickened peripheral nerves, and acid-fast bacilli detected on skin
      smears or biopsy material. M. leprae primarily infects Schwann cells in the
      peripheral nerves leading to nerve damage and the development of disabilities.
      Despite reduced prevalence of M. leprae infection in the endemic countries
      following implementation of multidrug therapy (MDT) program by WHO to treat
      leprosy, new case detection rates are still high-indicating active transmission.
      The susceptibility to the mycobacteria and the clinical course of the disease are
      attributed to the host immune response, which heralds the review of
      immunopathology of this complex disease.

PMID- 22988459
TI  - Light modulates leptin and ghrelin in sleep-restricted adults.
AB  - Acute and chronic sleep restrictions cause a reduction in leptin and an increase
      in ghrelin, both of which are associated with hunger. Given that light/dark
      patterns are closely tied to sleep/wake patterns, we compared, in a within
      subjects study, the impact of morning light exposures (60 lux of 633-nm [red],
      532-nm [green], or 475-nm [blue] lights) to dim light exposures on leptin and
      ghrelin concentrations after subjects experienced 5 consecutive days of both an 8
      hour (baseline) and a 5-hour sleep-restricted schedule. In morning dim light, 5
      hour sleep restriction significantly reduced leptin concentrations compared to
      the baseline, 8-hour sleep/dim-light condition (t(1,32) = 2.9; P = 0.007).
      Compared to the 5-hour sleep/dim-light condition, the red, green, and blue
      morning light exposures significantly increased leptin concentrations (t(1,32) =
      5.7; P < 0.0001, t(1,32) = 3.6; P = 0.001, and t(1,32) = 3.0; P = 0.005, resp.).
      Morning red light and green light exposures significantly decreased ghrelin
      concentrations (t(1,32) = 3.3; P < 0.003 and t(1,32) = 2.2; P = 0.04, resp.), but
      morning blue light exposures did not. This study is the first to demonstrate that
      morning light can modulate leptin and ghrelin concentrations, which could have an
      impact on reducing hunger that accompanies sleep deprivation.

PMID- 22988458
TI  - Integrated Tools for American Cutaneous Leishmaniasis Surveillance and Control:
      Intervention in an Endemic Area in Rio de Janeiro, RJ, Brazil.
AB  - American cutaneous leishmaniasis (ACL) is a focal disease whose surveillance and
      control require complex actions. The present study aimed to apply integrated
      tools related to entomological surveillance, environmental management, and health
      education practices in an ACL-endemic area in Rio de Janeiro city, RJ, Brazil.
      The distribution of the disease, the particular characteristics of the
      localities, and entomological data were used as additional information about ACL
      determinants. Environmental management actions were evaluated after health
      education practices. The frequency of ACL vectors Lutzomyia (N.) intermedia and
      L. migonei inside and outside houses varied according to environment
      characteristics, probably influenced by the way of life of the popular groups. In
      this kind of situation environmental management and community mobilization become
      essential, as they help both specialists and residents create strategies that can
      interfere in the dynamics of vector's population and the contact between man and
      vectors.

PMID- 22988460
TI  - Perfusion flow enhances osteogenic gene expression and the infiltration of
      osteoblasts and endothelial cells into three-dimensional calcium phosphate
      scaffolds.
AB  - Maintaining cellular viability in vivo and in vitro is a critical issue in three
      dimensional bone tissue engineering. While the use of osteoblast/endothelial cell
      cocultures on three-dimensional constructs has shown promise for increasing in
      vivo vascularization, in vitro maintenance of cellular viability remains
      problematic. This study used perfusion flow to increase osteogenic and angiogenic
      gene expression, decrease hypoxic gene expression, and increase cell and matrix
      coverage in osteoblast/endothelial cell co-cultures. Mouse osteoblast-like cells
      (MC3T3-E1) were cultured alone and in co-culture with mouse microvascular
      endothelial cells (EOMA) on three-dimensional scaffolds for 1, 2, 7, and 14 days
      with or without perfusion flow. mRNA levels were determined for several
      osteogenic, angiogenic, and hypoxia-related genes, and histological analysis was
      performed. Perfusion flow downregulated hypoxia-related genes (HIF-1alpha, VEGF,
      and OPN) at early timepoints, upregulated osteogenic genes (ALP and OCN) at 7
      days, and downregulated RUNX-2 and VEGF mRNA at 14 days in osteoblast
      monocultures. Perfusion flow increased cell number, coverage of the scaffold
      perimeter, and matrix area in the center of scaffolds at 14 days. Additionally,
      perfusion flow increased the length of endothelial cell aggregations within co
      cultures. These suggest perfusion stimulated co-cultures provide a means of
      increasing osteogenic and angiogenic activity.

PMID- 22988461
TI  - Auditory brainstem responses to bone-conducted brief tones in young children with
      conductive or sensorineural hearing loss.
AB  - The bone-conduction (BC) tone ABR has been used clinically for over 20 years. The
      current study formally evaluated the test performance of the BC tone-evoked ABR
      in infants with hearing loss. Method. By comparing BC-ABR results to follow-up
      behavioural results, this study addressed two questions: (i) whether the BC tone
      ABR was successful in differentiating children with conductive versus
      sensorineural hearing loss (Study A; conductive: 68 ears; SNHL: 129 ears) and
      (ii) the relationship between BC ABR and behavioural hearing loss severity (Study
      B: 2000 Hz: 104 ears; 500 Hz: 47 ears). Results. Results demonstrate that the
      "normal" BC-ABR levels accurately differentiated normal versus elevated cochlear
      sensitivity (accuracy: 98% for 2000 Hz; 98% for 500 Hz). A subset of infants in
      Study A with elevated BC-ABR (i.e., no response at normal level) had additional
      testing at higher intensities, which allowed for categorization of the degree of
      cochlear impairment. Study B results indicate that the BC ABR accurately
      categorizes the degree of cochlear hearing loss for 2000 Hz (accuracy = 95.2%). A
      preliminary dBnHL-to-dBHL correction factor of "0 dB" was determined for 2000 Hz
      BC ABR. Conclusions. These findings further support the use of BC tone ABR for
      diagnostic ABR testing.

PMID- 22988463
TI  - Painless Livedoid Vasculopathy in a Patient with G20210A Prothrombin Gene
      Mutation.
AB  - 87 year old Caucasian female with chronic painless non-healing ulcers over
      malleoli was admitted to the hospital. On a physical examination, there were two
      bilateral and laterally located malleoli ulcers with no discharge. A thorough
      work up was done: lower extremities venous and arterial Doppler ultrasound did
      not show any evidence of venous and arterial disease respectively. Heterozygous
      G20210A Prothrombin gene mutation was found, and the patient was started on
      anticoagulation. This case reports highlights a possibility of a painless
      livedoid vasculopathy presentation in a patient without significant past
      thrombotic events. Therefore, it is important to consider livedoid vasculopathy
      in the differential in a patient with painless ulcerative, atrophic and/or
      nodular skin lesions over the shins and malleoli.

PMID- 22988462
TI  - Circulating biomarkers of interstitial lung disease in systemic sclerosis.
AB  - Interstitial lung disease (ILD) is a major cause of morbidity and mortality in
      patients with systemic sclerosis (SSc). Although a large proportion of SSc
      patients have only limited interstitial involvement with an indolent course, in a
      significant minority ILD is progressive, requiring prompt treatment and careful
      monitoring. One of the main challenges for the clinician treating this highly
      variable disease is the early identification of patients at risk of progressive
      ILD, while avoiding potentially toxic treatments in those whose disease is
      inherently stable. Easily available and repeatable biomarkers that allow
      estimation of the risk of ILD progression and early response to treatment are
      highly desirable. In this paper, we review the evidence for circulating
      biomarkers with potential roles in diagnosis, monitoring of disease activity, or
      determining prognosis. Peripheral blood biomarkers offer the advantages of being
      readily obtained, non-invasive, and serially monitored. Several possible
      candidates have emerged from studies performed so far, including SP-D, KL-6, and
      CCL18. Presently however, there are few prospective studies evaluating the
      predictive ability of prospective biomarkers after adjustment for disease
      severity. Future carefully designed, prospective studies of well characterised
      patients with ILD, with optimal definition of disease severity and outcome
      measures are needed.

PMID- 22988466
TI  - Variation in malaria transmission dynamics in three different sites in Western
      kenya.
AB  - The main objective was to investigate malaria transmission dynamics in three
      different sites, two highland villages (Fort Ternan and Lunyerere) and a lowland
      peri-urban area (Nyalenda) of Kisumu city. Adult mosquitoes were collected using
      PSC and CDC light trap while malaria parasite incidence data was collected from a
      cohort of children on monthly basis. Rainfall, humidity and temperature data were
      collected by automated weather stations. Negative binomial and Poisson
      generalized additive models were used to examine the risk of being infected, as
      well as the association with the weather variables. Anopheles gambiae s.s. was
      most abundant in Lunyerere, An. arabiensis in Nyalenda and An. funestus in Fort
      Ternan. The CDC light traps caught a higher proportion of mosquitoes (52.3%) than
      PSC (47.7%), although not significantly different (P = 0.689). The EIR's were 0,
      61.79 and 6.91 bites/person/year for Fort Ternan, Lunyerere and Nyalenda. Site,
      month and core body temperature were all associated with the risk of having
      malaria parasites (P < 0.0001). Rainfall was found to be significantly associated
      with the occurrence of P. falciparum malaria parasites, but not relative humidity
      and air temperature. The presence of malaria parasite-infected children in all
      the study sites provides evidence of local malaria transmission.

PMID- 22988465
TI  - The insulin regulatory network in adult hippocampus and pancreatic endocrine
      system.
AB  - There is a very strong correlation between the insulin-mediated regulatory system
      of the central nervous system and the pancreatic endocrine system. There are many
      examples of the same transcriptional factors being expressed in both regions in
      their embryonic development stages. Hormonal signals from the pancreatic islets
      influence the regulation of energy homeostasis by the brain, and the brain in
      turn influences the secretions of the islets. Diabetes induces neuronal death in
      different regions of the brain especially hippocampus, causes alterations on the
      neuronal circuits and therefore impairs learning and memory, for which the
      hippocampus is responsible. The hippocampus is a region of the brain where steady
      neurogenesis continues throughout life. Adult neurogenesis from undifferentiated
      neural stem cells is greatly decreased in diabetic patients, and as a result
      their learning and memory functions decline. Might it be possible to reactivate
      stem cells whose functions have deteriorated and that are present in the tissues
      in which the lesions occur in diabetes, a lifestyle disease, which plagues modern
      humans and develops as a result of the behavior of insulin-related factor? In
      this paper we summarize research in regard to these matters based on examples in
      recent years.

PMID- 22988464
TI  - Cellular programming and reprogramming: sculpting cell fate for the production of
      dopamine neurons for cell therapy.
AB  - Pluripotent stem cells are regarded as a promising cell source to obtain human
      dopamine neurons in sufficient amounts and purity for cell replacement therapy.
      Importantly, the success of clinical applications depends on our ability to steer
      pluripotent stem cells towards the right neuronal identity. In Parkinson disease,
      the loss of dopamine neurons is more pronounced in the ventrolateral population
      that projects to the sensorimotor striatum. Because synapses are highly specific,
      only neurons with this precise identity will contribute, upon transplantation, to
      the synaptic reconstruction of the dorsal striatum. Thus, understanding the
      developmental cell program of the mesostriatal dopamine neurons is critical for
      the identification of the extrinsic signals and cell-intrinsic factors that
      instruct and, ultimately, determine cell identity. Here, we review how extrinsic
      signals and transcription factors act together during development to shape
      midbrain cell fates. Further, we discuss how these same factors can be applied in
      vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.

PMID- 22988467
TI  - Lithium Attenuates TGF-beta(1)-Induced Fibroblasts to Myofibroblasts Transition
      in Bronchial Fibroblasts Derived from Asthmatic Patients.
AB  - Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of
      bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial
      fibroblasts (HBFs) derived from patients with diagnosed asthma display
      predestination towards TGF-beta-induced phenotypic switches. Since the
      interference between TGF-beta and GSK-3beta signaling contributes to
      pathophysiology of chronic lung diseases, we investigated the effect of lithium,
      a nonspecific GSK-3beta inhibitor, on TGF-beta(1)-induced fibroblast to
      myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3beta
      attenuates TGF-beta(1)-induced FMT in HBF populations derived from asthmatic but
      not healthy donors. Cytoplasmically sequestrated beta-catenin, abundant in TGF
      beta(1)/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits
      the nuclear accumulation and signal transduction of Smad proteins. These data
      indicate that the specific cellular context determines FMT-related responses of
      HBFs to factors interfering with the TGF-beta signaling pathway. They may also
      provide a mechanistic explanation for epidemiological data revealing coincidental
      remission of asthmatic syndromes and their recurrence upon the discontinuation of
      lithium therapy in certain psychiatric diseases.

PMID- 22988468
TI  - Gene-expression-guided selection of candidate loci and molecular phenotype
      analyses enhance genetic discovery in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder
      characterized by differences in autoantibody profiles, serum cytokines, and
      clinical manifestations. We have previously conducted a case-case genome-wide
      association study (GWAS) of SLE patients to detect associations with autoantibody
      profile and serum interferon alpha (IFN-alpha). In this study, we used public
      gene expression data sets to rationally select additional single nucleotide
      polymorphisms (SNPs) for validation. The top 200 GWAS SNPs were searched in a
      database which compares genome-wide expression data to genome-wide SNP genotype
      data in HapMap cell lines. SNPs were chosen for validation if they were
      associated with differential expression of 15 or more genes at a significance of
      P < 9 * 10(-5). This resulted in 11 SNPs which were genotyped in 453 SLE patients
      and 418 matched controls. Three SNPs were associated with SLE-associated
      autoantibodies, and one of these SNPs was also associated with serum IFN-alpha (P
      < 4.5 * 10(-3) for all). One additional SNP was associated exclusively with serum
      IFN-alpha. Case-control analysis was insensitive to these molecular subphenotype
      associations. This study illustrates the use of gene expression data to
      rationally select candidate loci in autoimmune disease, and the utility of
      stratification by molecular phenotypes in the discovery of additional genetic
      associations in SLE.

PMID- 22988470
TI  - Efficacy of Boesenbergia rotunda Treatment against Thioacetamide-Induced Liver
      Cirrhosis in a Rat Model.
AB  - Background. Experimental research in hepatology has focused on developing
      traditional medicines into potential pharmacological solutions aimed at
      protecting liver from cirrhosis. Along the same line, this study investigated the
      effects of ethanol-based extract from a traditional medicine plant Boesenbergia
      rotunda (BR) on liver cirrhosis. Methodology/Results. The BR extract was tested
      for toxicity on 3 groups of rats subjected to vehicle (10% Tween 20, 5 mL/kg) and
      2g/kg and 5g/kg doses of the extract, respectively. Next, experiments were
      conducted on a rat model of cirrhosis induced by thioacetamide injection. The
      rats were divided into five groups and, respectively, administered orally with
      10% Tween-20 (5 mL/kg) (normal control group), 10% Tween-20 (5 mL/kg) (cirrhosis
      control group), 50 mg/kg of silymarin (reference control group), and 250 mg/kg
      and 500 mg/kg of BR extract (experimental groups) daily for 8 weeks. The rats in
      normal group were intraperitoneally injected with sterile distilled water (1
      mL/kg) 3 times/week, and those in the remaining groups were injected
      intraperitoneally with thioacetamide (200 mg/kg) thrice weekly. At the end of the
      8 weeks, the animals were sacrificed and samples were collected for comprehensive
      histopathological, coagulation profile and biochemical evaluations. Also, the
      antioxidant activity of the BR extract was determined and compared with that of
      silymarin. Data from the acute toxicity tests showed that the extract was safe to
      use. Histological analysis of the livers of the rats in cirrhosis control group
      revealed uniform coarse granules on their surfaces, hepatocytic necrosis, and
      lymphocytes infiltration. But, the surfaces morphologically looked much smoother
      and the cell damage was much lesser in those livers from the normal control,
      silymarin and BR-treated groups. In the high-dose BR treatment group, the livers
      of the rats exhibited nearly normal looking lobular architecture, minimal
      inflammation, and minimal hepatocyte damage, the levels of the serum biomarkers
      and liver enzymes read nearly normal, and these results were all comparable to
      those observed or quantified from the normal and silymarin-treated groups. The BR
      extract had the antioxidant activity about half of what was recorded for
      silymarin. Conclusion. The progression of the liver cirrhosis can be intervened
      using the ethanol-based BR extract, and the liver's status quo of property,
      structure, and function can be preserved. This capability of the extract warrants
      further studies exploring the significance of its pharmacologic potential in
      successfully treating the liver cirrhosis in humans.

PMID- 22988471
TI  - Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced
      Hematotoxicity in Mice.
AB  - The aim of the present study was to investigate the protective role of methanolic
      leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in
      Swiss albino mice. GC analysis and subacute toxicity level of the extract were
      tested. Mice were randomly divided into three groups among which II and III were
      exposed to benzene vapour at a dose 300 ppm * 6 hr/day * 5 days/week for 2 weeks
      and group I was control. Group III of this experiment was treated with the leaf
      methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range.
      Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory
      proteins expression and DNA fragmentation analysis of bone marrow cells was
      performed. There was an upregulation of p53 and p21 and downregulation of levels
      of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was
      less fragmented in group III compared to group II (P < 0.05). The present study
      indicates that the secondary metabolites of O. basilicum L. methanolic leaf
      extract, comprising essential oil monoterpene geraniol and its oxidized form
      citral as major constituents, have modulatory effect in cell cycle deregulation
      and hematological abnormalities induced by benzene in mice.

PMID- 22988472
TI  - High-tech acupuncture and integrative laser medicine.

PMID- 22988469
TI  - Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus
      infection.
AB  - Patients with chronic hepatitis C virus (HCV) infection frequently have many
      extrahepatic manifestations, as persistent HCV infection often triggers
      lymphoproliferative disorders and metabolic abnormalities. These manifestations
      primarily include autoimmune disorders such as cryoglobulinemia, Sjogren's
      syndrome, and autoimmune thyroid disorders. It has been well established that
      chronic HCV infection plays important roles in the production of non-organ
      specific autoantibodies, including antinuclear antibodies and smooth muscle
      antibodies, and organ-specific autoantibodies such as thyroid autoantibodies.
      However, the clinical significance of autoantibodies associated with the
      extrahepatic manifestations caused by HCV infection has not been fully
      recognized. In this paper, we mainly focus on the relationship between
      extrahepatic manifestations and the emergence of autoantibodies in patients with
      HCV infection and discuss the clinical relevance of the autoantibodies in the
      extrahepatic disorders.

PMID- 22988473
TI  - Single agent polysaccharopeptide delays metastases and improves survival in
      naturally occurring hemangiosarcoma.
AB  - The 2008 World Health Organization World Cancer Report describes global cancer
      incidence soaring with many patients living in countries that lack resources for
      cancer control. Alternative treatment strategies that can reduce the global
      disease burden at manageable costs must be developed. Polysaccharopeptide (PSP)
      is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate
      PSP has in vitro antitumor activities and inhibits the growth of induced tumors
      in animal models. Clear evidence of clinically relevant benefits of PSP in cancer
      patients, however, is lacking. The investment of resources required to complete
      large-scale, randomized controlled trials of PSP in cancer patients is more
      easily justified if antitumor and survival benefits are documented in a complex
      animal model of a naturally occurring cancer that parallels human disease.
      Because of its high metastatic rate and vascular origin, canine hemangiosarcoma
      is used for investigations in antimetastatic and antiangiogenic therapies. In
      this double-blind randomized multidose pilot study, high-dose PSP significantly
      delayed the progression of metastases and afforded the longest survival times
      reported in canine hemangiosarcoma. These data suggest that, for those cancer
      patients for whom advanced treatments are not accessible, PSP as a single agent
      might offer significant improvements in morbidity and mortality.

PMID- 22988475
TI  - Anti-Inflammatory Effect of Triterpene Saponins Isolated from Blue Cohosh
      (Caulophyllum thalictroides).
AB  - Blue cohosh has been used as a medicinal herb in eastern North America. It was
      commonly used as traditional medicines for the treatment of menopausal symptoms,
      rheumatic pain, and as anti-inflammatory remedy. Particularly, extract of blue
      cohosh roots has been used as anti-inflammatory antipyretic in traditional
      medicines. In the present study, we investigated the effects of blue cohosh
      components on the suppressive expression of iNOS or proinflammatory cytokines
      after the activation of microglia with lipopolysaccharide (LPS). The expression
      of iNOS, TNF-alpha, IL-1beta, and IL-6 was determined by western blotting or gene
      expression. Blue cohosh treatment suppressed the elevation of LPS-induced iNOS
      expression in a concentration-dependent manner in microglia cells. Blue cohosh
      constituents also suppressed the expression of TNF-alpha, IL-1beta, and IL-6. In
      addition, blue cohosh extract suppressed the expression of COX-2, iNOS, and
      proinflammatory cytokines in adrenal glands of mice. These results demonstrate
      that constituents of blue cohosh exert anti-inflammatory effects through the
      inhibition of expression of iNOS and proinflammatory cytokines. Therefore, blue
      cohosh may have therapeutic potential for the treatment of inflammation-related
      diseases.

PMID- 22988476
TI  - Coral-Associated Bacteria as a Promising Antibiofilm Agent against Methicillin
      Resistant and -Susceptible Staphylococcus aureus Biofilms.
AB  - The current study deals with the evaluation of two coral-associated bacterial
      (CAB) extracts to inhibit the biofilm synthesis in vitro as well as the virulence
      production like hemolysin and exopolysaccharide (EPS), and also to assess their
      ability to modify the adhesion properties, that is cell surface hydrophobicity
      (CSH) of methicillin-resistant (MRSA) and -susceptible Staphylococcus aureus
      (MSSA). Out of nine CAB screened, the ethyl acetate extract of CAB-E2 (Bacillus
      firmus) and CAB-E4 (Vibrio parahemolyticus) have shown excellent antibiofilm
      activity against S. aureus. CAB-E2 reduced the production of EPS (57-79%) and
      hemolysin (43-70%), which ultimately resulted in the significant inhibition of
      biofilms (80-87%) formed by both MRSA and MSSA. Similarly, CAB-E4 was also found
      to decrease the production of EPS (43-57%), hemolysin (43-57%) and biofilms (80
      85%) of test pathogens. CLSM analysis also proved the antibiofilm efficacy of CAB
      extracts. Furthermore, the CAB extracts strongly decreased the CSH of S. aureus.
      Additionally, FT-IR analysis of S. aureus treated with CAB extracts evidenced the
      reduction in cellular components compared to their respective controls. Thus, the
      present study reports for the first time, B. firmus-a coral-associated bacterium,
      as a promising source of antibiofilm agent against the recalcitrant biofilms
      formed by multidrug resistant S. aureus.

PMID- 22988474
TI  - Alkaloids isolated from natural herbs as the anticancer agents.
AB  - Alkaloids are important chemical compounds that serve as a rich reservoir for
      drug discovery. Several alkaloids isolated from natural herbs exhibit
      antiproliferation and antimetastasis effects on various types of cancers both in
      vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already
      been successfully developed into anticancer drugs. This paper focuses on the
      naturally derived alkaloids with prospective anticancer properties, such as
      berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and
      summarizes the mechanisms of action of these compounds. Based on the information
      in the literature that is summarized in this paper, the use of alkaloids as
      anticancer agents is very promising, but more research and clinical trials are
      necessary before final recommendations on specific alkaloids can be made.

PMID- 22988477
TI  - Viscum album L. Extracts Protects HeLa Cells against Nuclear and Mitochondrial
      DNA Damage.
AB  - Viscum album L. is a semiparasitic plant grown on trees and widely used for the
      treatment of many diseases in traditional and complementary therapy. It is well
      known that some activities of Viscum album extracts are varied depending on the
      host trees, such as antioxidant, apoptosis-inducing, anticancer activities of the
      plant. The aim of the present study is to examine the comparative effects of
      methanolic extracts of V. album grown on three different host trees (locust tree,
      lime tree, and hedge maple tree) on H(2)O(2)-induced DNA damage in HeLa cells.
      Oxidative damage in mitochondrial DNA and two nuclear regions was assessed by
      QPCR assay. The cells were pretreated with methanolic extracts (10 MUg/mL) for 48
      h, followed by the treatment with 750 MUM H(2)O(2) for 1 hour. DNA damage was
      significantly induced by H(2)O(2) while it was inhibited by V. album extracts.
      All extracts completely protected against nuclear DNA damage. While the extract
      from lime tree or white locust tree entirely inhibited mitochondrial DNA damage,
      that from hedge maple tree inhibited by only 50%. These results suggest that
      methanolic extracts of V. album can prevent oxidative DNA damage, and the
      activity is dependent on the host tree.

PMID- 22988478
TI  - Evaluation of chinese-herbal-medicine-induced herb-drug interactions: focusing on
      organic anion transporter 1.
AB  - The consumption of Chinese herbal medicines (CHMs) is increasing exponentially.
      Many patients utilize CHMs concomitantly with prescription drugs in great
      frequency. Herb-drug interaction has hence become an important focus of study.
      Transporter-mediated herb-drug interactions have the potential to seriously
      influence drug efficacy and toxicity. Since organic anion transporter 1 (OAT1) is
      crucial in renal active secretion and drug-drug interactions, the possibility of
      modulation of OAT1-mediated drug transport should be seriously concerned. Sixty
      three clinically used CHMs were evaluated in the study. An hOAT1-overexpressing
      cell line was used for the in vitro CHMs screening, and the effective candidates
      were administered to Wistar rats to access renal hemodynamics. The regulation of
      OAT1 mRNA expression was also examined for further evidence of CHMs affecting
      OAT1-mediated transport. Among all the 63 CHMs, formulae Gui Zhi Fu Ling Wan (GZ)
      and Chia Wei Hsiao Yao San (CW) exhibited significant inhibitions on hOAT1
      mediated [(3)H]-PAH uptake in vitro and PAH clearance and net secretion in vivo.
      Moreover, GZ showed concentration-dependent manners both in vitro and in vivo,
      and the decrease of rOAT1 mRNA expression indicated that GZ not only inhibited
      function of OAT1 but also suppressed expression of OAT1.

PMID- 22988479
TI  - Microdosimetry for targeted alpha therapy of cancer.
AB  - Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to
      individual cancer cells while reducing the dose to normal tissues. TAT
      applications relate to hematologic malignancies and now extend to solid tumors.
      Results from several clinical trials have shown efficacy with limited toxicity.
      However, the dosimetry for the labeled alpha particle is challenging because of
      the heterogeneous antigen expression among cancer cells and the nature of short
      range, high-LET alpha radiation. This paper demonstrates that it is inappropriate
      to investigate the therapeutic efficacy of TAT by macrodosimetry. The objective
      of this work is to review the microdosimetry of TAT as a function of the cell
      geometry, source-target configuration, cell sensitivity, and biological factors.
      A detailed knowledge of each of these parameters is required for accurate
      microdosimetric calculations.

PMID- 22988480
TI  - Extraction of lesion-partitioned features and retrieval of contrast-enhanced
      liver images.
AB  - The most critical step in grayscale medical image retrieval systems is feature
      extraction. Understanding the interrelatedness between the characteristics of
      lesion images and corresponding imaging features is crucial for image training,
      as well as for features extraction. A feature-extraction algorithm is developed
      based on different imaging properties of lesions and on the discrepancy in
      density between the lesions and their surrounding normal liver tissues in triple
      phase contrast-enhanced computed tomographic (CT) scans. The algorithm includes
      mainly two processes: (1) distance transformation, which is used to divide the
      lesion into distinct regions and represents the spatial structure distribution
      and (2) representation using bag of visual words (BoW) based on regions. The
      evaluation of this system based on the proposed feature extraction algorithm
      shows excellent retrieval results for three types of liver lesions visible on
      triple-phase scans CT images. The results of the proposed feature extraction
      algorithm show that although single-phase scans achieve the average precision of
      81.9%, 80.8%, and 70.2%, dual- and triple-phase scans achieve 86.3% and 88.0%.

PMID- 22988482
TI  - The impact of early re-resection in patients with pT1 high-grade non-muscle
      invasive bladder cancer.
AB  - AIM: To evaluate the impact of early re-resection on the incidence of tumour
      recurrence and progression in patients with pT1 high-grade non-muscle invasive
      bladder cancer (HG-NMIBC). PATIENTS AND METHODS: From 2001 to 2008, 486
      consecutive patients were diagnosed with pT1 HG-NMIBC. Data were collected
      retrospectively which included patient demographics, histological parameters
      including the presence of detrusor muscle at initial TUR and at re-resection,
      adjuvant intravesical therapy, and recurrence and progression rates. Early re
      resection was performed within six weeks of initial TUR. Patients comprised those
      who underwent an early re-resection (Group A, n = 172) and those who did not
      (Group B, n = 314). RESULTS: At initial TUR, detrusor muscle was present in 61%
      (n = 105) of patients in Group A and 76% (n = 240) of patients in Group B. At
      early re-resection, detrusor muscle was present in 77.9% of cases. A residual
      tumour was present in 54.6% of re-resected cases. The overall incidence of tumour
      recurrence was 35% and 42% in Groups A and B, respectively. During follow-up,
      there was a significantly higher rate of tumour stage progression in patients who
      did not undergo early re-resection (Group B 14.4% vs. Group A 3.3%, P < 0.05).
      CONCLUSIONS: Early re-resection facilitates accurate staging and clearance of
      residual disease. Subsequent rates of tumour stage progression are significantly
      improved. We advocate early re-resection for all patients with HG-NMIBC.

PMID- 22988481
TI  - BIOMARKERS OF OPERATIONAL TOLERANCE IN SOLID ORGAN TRANSPLANTATION.
AB  - INTRODUCTION: Long-term immunosuppressive therapy represents a huge burden on
      transplant recipients, but currently cannot be omitted. Improving long-term
      transplant outcome by immunosuppressive drug withdrawal may be achieved in
      patients who have developed (partial) immunological unresponsiveness towards
      their graft, either spontaneously or through tolerance induction. Reliable
      biomarkers are essential to define such immunological unresponsiveness and will
      facilitate controlled immunosuppressive drug weaning as well as provide surrogate
      end-points for tolerance induction trials.  AREAS COVERED: Tolerance biomarkers
      have been defined for both liver and kidney transplantation and can accurately
      identify operationally tolerant transplant recipients retrospectively. These two
      tolerance fingerprints are remarkably different, indicating the involvement of
      distinct mechanisms. Limited data suggest that tolerance biomarkers can be
      detected in immunosuppressed transplant recipients. Whether these patients can
      safely have their immunosuppressive drugs withdrawn needs to be established. 
      EXPERT OPINION: Mechanistic interpretation of the kidney transplant tolerance
      biomarker profile dominated by B cell markers remains a challenge in light of
      experimental evidence suggesting the pivotal involvement of regulatory T cells.
      Therefore, defining animal models that resemble human transplant tolerance is
      crucial in understanding the underlying mechanisms. Additionally, to ensure
      patient safety while monitoring for tolerance, it is essential to develop
      biomarkers to non-invasively detect early signs of rejection as well.

PMID- 22988483
TI  - Oxygen concentration-dependent oxidative stress levels in rats.
AB  - INTRODUCTION: We determined derivatives of reactive oxygen metabolites (dROMs) as
      an index of oxidative stress level (oxidant capacity) and biochemical antioxidant
      potential (BAP) as an index of antioxidant capacity in rats exposed to different
      oxygen concentrations. METHODS: Male Wistar rats were exposed to 14.4%, 20.9%,
      35.5%, 39.8%, 62.5%, and 82.2% oxygen at 1 atmosphere absolute for 24 h. Serum
      levels of dROMs and BAP were examined by using a free radical and antioxidant
      potential determination device. The morphological characteristics of red blood
      cells were examined by phase contrast microscopy. RESULTS: There were no
      differences in the levels of dROMs in rats exposed to 14.4%, 20.9%, and 35.5%
      oxygen. However, the levels of dROMs increased in the rats exposed to 39.8% and
      62.5% oxygen. The levels of dROMs were the highest in the rats exposed to 82.2%
      oxygen. There were no differences in the levels of BAP with respect to the oxygen
      concentration. Morphological changes in the red blood cells induced by oxidative
      attack from reactive oxygen species were observed in the rats exposed to 39.8%,
      62.5%, and 82.2% oxygen. CONCLUSION: Our results suggest that exposure to oxygen
      concentrations higher than 40% for 24 h induces excessive levels of oxidative
      stress in rats.

PMID- 22988484
TI  - Evaluation of protocol biopsy utility 12 months after renal transplantation: a
      multicenter observational analysis.
AB  - The clinical merit of surveillance kidney graft biopsies remains controversial. A
      retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB,
      154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in
      patients >18 months posttransplant with estimated GFR (eGFR) >=30 mL/min. The
      primary objective was to describe renal function at 18 months post-transplant in
      patients with or without SB at month 12. Globally, most recipients in both
      cohorts were at low immunological risk (<10% of patients with PRA >=30%). The
      immunosuppressive regimen remained unchanged following more than half of SB that
      exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary
      endpoint) was 56 (19) mL/min/1.73 m2 with SB and 54 (15) mL/min/1.73 m2 with NSB
      (P = 0.48). In the SB group, slight nonspecific changes were observed in 51
      cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases,
      recurrence of initial disease in two cases, and interstitial fibrosis/tubular
      atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III
      lesions. eGFR <50 mL/min/1.73 m2 at month 6 predicted IF/TA grade II or III (OR
      3.85, 95% CI 1.64, 9.05, P < 0.002). SB at 12 months posttransplant did not
      prompt significant modification of immunosuppression, and no renal benefit was
      observed.

PMID- 22988485
TI  - Reduced heart rate recovery is associated with poorer cognitive function in older
      adults with cardiovascular disease.
AB  - Cardiovascular disease (CVD) in older adults has been associated with varying
      degrees of cognitive dysfunction. Several mechanisms may explain this
      association, including impaired cardiovascular reactivity to autonomic nervous
      system (ANS) signaling. Reduced heart rate recovery following a stress test may
      be considered an indication of impaired ANS function (i.e., reduced
      parasympathetic activity). Participants were 47 older adults (53-83 years) who
      underwent a treadmill stress test and were administered a comprehensive
      neuropsychological battery upon entry to phase II cardiac rehabilitation. Reduced
      parasympathetic activity was associated with impaired cognitive performance on a
      measure of global cognitive function and on tasks of speeded executive function
      and confrontation naming. These relationships suggest that changes in autonomic
      function may be mechanistically related to the impaired cognitive function
      prevalent in CVD patients.

PMID- 22988486
TI  - Allelic Imbalance in TOR1A mRNA Expression in Manifesting and Non-Manifesting
      Carriers of the GAG-Deletion.
AB  - Early onset dystonia (EOD) is associated with a 3bp-(DeltaGAG) in-frame deletion
      in the TOR1A gene, which encodes for torsinA. Carriers of the mutant (DeltaGAG)
      allele can either develop or escape a dystonic phenotype (~30% penetrance). The
      expression ratio of the two alleles could be important for the manifestation or
      prevention of the disease since wild-type (WT) torsinA is thought to have
      protective function. Absence of an antibody discriminating WT from DeltaE torsinA
      has precluded the determination DeltaE and WT torsinA levels in manifesting and
      nonmanifesting carriers. We performed quantitative analysis of TOR1A allele
      expression in manifesting (MC) and nonmanifesting (NMC) carriers using
      quantitative allele-specific PCR (qASPCR) to determine the levels of mutant
      versus WT torsinA mRNA. The technique described showed high degree of specificity
      in detecting the two alleles. The present study represents the first
      comprehensive analysis of biallelic expression of the TOR1A gene in lymphoblast
      and brain samples from patients and NMC relatives. We demonstrate that mRNA is
      transcribed from both the WT and DeltaGAG allele in peripheral and neural tissues
      with a trend for increased expression of the DeltaGAG allele compared to the WT
      in carriers regardless of their phenotype and thus cannot account for the reduced
      penetrance.

PMID- 22988488
TI  - Cognition and vascular risk factors: an epidemiological study.
AB  - We conducted an epidemiological approach to identify the negative impact of the
      vascular risk factors (such as hypertension, diabetes and hypercholesterolemia)
      over cognition. The interesting aspect of this study was that the survey was
      conducted in all age groups through a voluntary call (n = 1365; >=18 years old,
      both sexes; age 49 +/- 15 y, female 75.7%). Thus, we demonstrated that the use of
      a Minimum Cognitive Examination (MCE), a brief, simple, and easy managed
      neuropsychological evaluation, detected a greater number of people with cognitive
      decline surpassing to the Minimal Mental Statement Examination alone (14.5% of
      the participants showed MMSE <=24, 34,6% showed dys-executive function, and 45,8%
      memory impairment. Out of the 4 studied RF, the only one that was not related to
      cognitive impairment was dyslipemia. Finally, we noted the importance of
      cognitive state early detection in all age groups, even in the youngest group.
      Acting in the middle of the life stages, we can prevent or delay the onset of a
      disease in adults, nowadays incurable: dementia.

PMID- 22988490
TI  - Obesity and pulmonary hypertension: a review of pathophysiologic mechanisms.
AB  - Pulmonary hypertension (PH) is a potentially life-threatening condition arising
      from a wide variety of pathophysiologic mechanisms. Effective treatment requires
      a systematic diagnostic approach to identify all reversible mechanisms. Many of
      these mechanisms are relevant to those afflicted with obesity. The unique
      mechanisms of PH in the obese include obstructive sleep apnea, obesity
      hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and
      pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include
      endothelial dysfunction and hyperuricemia. A wide range of effective therapies
      exist to mitigate the disability of PH in the obese.

PMID- 22988489
TI  - Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and
      Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort.
AB  - Purpose. This study evaluates high-throughput autoantibody screening and
      determines associated systemic lupus erythematosus (SLE) clinical features in a
      large lupus cohort. Methods. Clinical and demographic information, along with
      serum samples, were obtained from each SLE study participant after appropriate
      informed consent. Serum samples were screened for 10 distinct SLE autoantibody
      specificities and examined for association with SLE ACR criteria and subcriteria
      using conditional logistic regression analysis. Results. In European-American SLE
      patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched
      in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in
      patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients
      with proteinuria. In African-American SLE patients, cellular casts associate with
      autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high
      throughput, bead-based method of autoantibody detection, anti-dsDNA is
      significantly enriched in patienets with SLE ACR renal criteria as has been
      previously described. However, lymphopenia is associated with several distinct
      autoantibody specificities. These findings offer meaningful information to allow
      clinicians and clinical investigators to understand which autoantibodies
      correlate with select SLE clinical manifestations across common racial groups
      using this novel methodology which is expanding in clinical use.

PMID- 22988491
TI  - Fruit and vegetable intake in adolescents: association with socioeconomic status
      and exposure to supermarkets and fast food outlets.
AB  - Background. We investigated differences in family social class associations
      between food outlet exposure and fruit and vegetable intake. Methods. We
      supplemented data from the 2006 Health Behavior in School Aged Children Study (n
      = 6, 096) with geocoded food outlet information surrounding schools (n = 80). We
      used multilevel logistic regression to examine associations between infrequent
      fruit and vegetable intake and supermarket and fast food outlet concentration,
      stratified by family social class. Results. Boys and older children were most
      likely to eat fruit and vegetables infrequently. High fast food outlet exposure
      was marginally significant for low fruit intake in low social class children
      only. Children from middle and low social class backgrounds attending schools
      with combined high fast food outlet/low supermarket exposure were most likely to
      report infrequent fruit intake (OR(low) = 1.60; CI:  1.02-2.45; OR(mid) = 1.40;
      CI:  1.03-190). Children from low social class backgrounds were also likely to
      report infrequent vegetable intake, given low supermarket and high fast food
      outlet exposure (OR = 1.79; CI:  0.99-3.21). Conclusion. Our findings suggest
      social class modifies the relationship between intake and food outlet
      concentration. School interventions improving fruit and vegetable intake should
      consider neighborhood surroundings, targetting older children from low social
      class backgrounds.

PMID- 22988493
TI  - Reduced PKC alpha Activity Induces Senescent Phenotype in Erythrocytes.
AB  - The molecular mechanism mediating expression of senescent cell antigen-aggregated
      or cleaved band 3 and externalized phosphatidylserine (PS) on the surface of aged
      erythrocytes and their premature expression in certain anemias is not completely
      elucidated. The erythrocytes with these surface modifications undergo macrophage
      mediated phagocytosis. In this study, the role of protein kinase C (PKC) isoforms
      in the expression of these surface modifications was investigated. Inhibition of
      PKC alpha by 30 MUM rottlerin (R30) and 2.3 nM Go 6976 caused expression of both
      the senescent cell marker-externalized PS measured by FACS analysis and
      aggregated band 3 detected by western blotting. In contrast to this observation,
      but in keeping with literature, PKC activation by phorbol-12-myristate-13-acetate
      (PMA) also led to the expression of senescence markers. We explain this
      antithesis by demonstrating that PMA-treated cells show reduction in the activity
      of PKC alpha, thereby simulating inhibition. The reduction in PKC alpha activity
      may be attributed to the known downregulation of PMA-activated PKC alpha, caused
      by its membrane translocation and proteolysis. We demonstrate membrane
      translocation of PKC alpha in PMA-treated cells to substantiate this inference.
      Thus loss of PKC alpha activity either by inhibition or downregulation can cause
      surface modifications which can trigger erythrophagocytosis.

PMID- 22988492
TI  - Partial replacement with menhaden oil improves peripheral neuropathy in high-fat
      fed low-dose streptozotocin type 2 diabetic rat.
AB  - Aims. To determine the effect of partial replacement of a high-fat diet with
      menhaden oil on diabetic neuropathy in an animal model of type 2 diabetes.
      Materials and Methods. High-fat/low-dose streptozotocin diabetic rats were used
      to examine the influence of replacing 50% of the source of the high-fat diet
      (lard) with menhaden oil, a natural source of n-3 fatty acids, on diabetic
      neuropathy. Endpoints included analyses of glucose tolerance, fatty liver
      disease, serum and liver fatty acid composition, serum lipid and adiponectin
      levels, motor and sensory nerve conduction velocity, thermal sensitivity and
      innervation of the hindpaw. Results. Diabetic rats were insulin resistant and
      menhaden oil did not improve whole animal glucose utilization. Menhaden oil did
      not improve elevated HbA(1)C levels or serum lipid levels but serum levels of
      adiponectin were significantly increased and hepatic steatosis was significantly
      improved. Diabetic rats were thermal hypoalgesic, had reduced motor and sensory
      nerve conduction velocities and intraepidermal nerve fiber profiles were
      decreased in the hindpaw and these endpoints were significantly improved with
      menhaden oil. Conclusions. We found that enrichment of a high-fat diet with
      menhaden oil improved a number of endpoints associated with diabetic neuropathy.

PMID- 22988494
TI  - Consumer Feedback following Participation in a Family-Based Intervention for
      Youth Mental Health.
AB  - Background. This paper presents findings derived from consumer feedback,
      following a multicentre randomised controlled trial for adolescent mental health
      problems and substance misuse. The paper focuses on the implementation of a
      family-based intervention, including fidelity of delivery, family members'
      experiences, and their suggestions for program improvements. Methods. Qualitative
      and quantitative data (n = 21) were drawn from the Deakin Family Options trial
      consumer focus groups, which occurred six months after the completion of the
      trial. Consumer focus groups were held in both metropolitan and regional
      locations in Victoria, Australia. Findings. Overall reductions in parental
      isolation, increases in parental self-care, and increased
      separation/individuation were the key therapeutic features of the intervention.
      Sharing family experiences with other parents was a key supportive factor, which
      improved parenting confidence and efficacy and potentially reduced family
      conflict. Consumer feedback also led to further development of the intervention,
      with a greater focus on aiding parents to engage adolescents in services and
      addressing family factors related to adolescent's mood and anxiety symptoms.
      Conclusions. Participant feedback provides valuable qualitative data, to monitor
      the fidelity of treatment implementation within a trial, to confirm predictions
      about the effective mechanisms of an intervention, and to inform the development
      of new interventions.

PMID- 22988496
TI  - Resection of nonalcoholic steatohepatitis-associated hepatocellular carcinoma: a
      Western experience.
AB  - Introduction. Hepatocellular carcinoma is now known to arise in association with
      nonalcoholic steatohepatitis. The aim of this study is to examine the
      clinicopathological features of this entity using liver resection cases at a
      large Western center. Methods. We retrospectively reviewed all cases of partial
      liver resection for hepatocellular carcinoma over a 10-year period. We included
      for the purpose of this study patients with histological evidence of nonalcoholic
      steatohepatitis and excluded patients with other chronic liver diseases such as
      viral hepatitis and alcoholic liver disease. Results. We identified 9 cases in
      which malignancy developed against a parenchymal background of histologically
      active nonalcoholic steatohepatitis. The median age at diagnosis was 58 (52-82)
      years, and 8 of the patients were male. Median body mass index was 30.2 (22.7
      39.4) kg/m(2). Hypertension was present in 77.8% of the patients and diabetes
      mellitus, obesity, and hyperlipidemia in 66.7%, respectively. The background
      liver parenchyma was noncirrhotic in 44% of the cases. Average tumor diameter was
      7.0 +/- 4.8 cm. Three-fourths of the patients developed recurrence within two
      years of resection, and 5-year survival was 44%. Conclusion. Hepatocellular
      carcinoma may arise in the context of nonalcoholic steatohepatitis, often before
      cirrhosis has developed. Locally advanced tumors are typical, and long-term
      failure rate following resection is high.

PMID- 22988497
TI  - Single-port access laparoscopy-assisted vaginal hysterectomy: our initial
      experiences with 100 cases.
AB  - Objectives. To present our initial experiences with laparoscopically assisted
      vaginal hysterectomy performed using homemade transumbilical single-port system.
      Materials and Methods. We reviewed the medical records of one hundred patients
      who underwent single-port access laparoscopically assisted vaginal hysterectomy
      (SPA-LAVH). SPA-LAVH was performed with homemade single port system and
      conventional rigid laparoscopic instruments. Results. All procedures were
      successfully completed through the single-port system and vagina without need for
      extraumbilical puncture or conversion to laparotomy. The median patient age was
      48.2 +/- 6.5 years. Thirty-three patients had history of past abdominopelvic
      surgery. The median total operative time, largest dimension of the uterus, and
      weight of the uterus were 73.1 +/- 24.6 min, 10.5 +/- 2.1 cm, and 300.8 +/- 192.5
      gram, respectively. The median decline in the hemoglobin from before surgery to
      postoperative day 1 was 1.8 +/- 0.9 g/dL. Bladder injury in occurred one patient
      who was repaired through intraoperative laparoscopic suture. The postoperative
      course was uneventful in most patients except for three who had a transient
      paralytic ileus, five who had pelvic hematoma, but they were recovered following
      conservative managements. No port-related complications were noted, and the
      cosmetic results were excellent. Conclusions. SPA-LAVH is technically safe
      procedure, and the homemade single-port system offers reliable access for single
      port surgery.

PMID- 22988495
TI  - Ductal carcinoma in situ of the breast: a surgical perspective.
AB  - Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous neoplasm with
      invasive potential. Risk factors include age, family history, hormone replacement
      therapy, genetic mutation, and patient lifestyle. The incidence of DCIS has
      increased due to more widespread use of screening and diagnostic mammography;
      almost 80% of cases are diagnosed with imaging with final diagnosis established
      by biopsy and histological examination. There are various classification systems
      used for DCIS, the most recent of which is based on the presence of
      intraepithelial neoplasia of the ductal epithelium (DIN). A number of molecular
      assays are now available that can identify high-risk patients as well as help
      establish the prognosis of patients with diagnosed DCIS. Current surgical
      treatment options include total mastectomy, simple lumpectomy in very low-risk
      patients, and lumpectomy with radiation. Adjuvant therapy is tailored based on
      the molecular profile of the neoplasm and can include aromatase inhibitors, anti
      estrogen, anti-progesterone (or a combination of antiestrogen and
      antiprogesterone), and HER2 neu suppression therapy. Chemopreventive therapies
      are under investigation for DCIS, as are various molecular-targeted drugs. It is
      anticipated that new biologic agents, when combined with hormonal agents such as
      SERMs and aromatase inhibitors, may one day prevent all forms of breast cancer.

PMID- 22988498
TI  - Reversible crystallization of argatroban after subcutaneous application in pigs.
AB  - Argatroban is a thrombin inhibitor used as anticoagulant in patients with heparin
      induced thrombocytopenia. It is usually administered as an intravenous bolus
      followed by infusion. Nevertheless, its pharmacokinetics after subcutaneous
      administration is unknown. The aim of this study was to assess the
      pharmacokinetics of two different formulations of argatroban in pigs after
      subcutaneous administration. Antithrombotic activity in plasma was determined by
      ecarin chromogenic assay. To visualize the formation of crystals, argatroban was
      administered to rats into the subcutaneous tissue exposed after removing the
      skin, and the injection site was photographed at different times. After
      subcutaneous administration of a sorbitol/ethanol formulation of argatroban in
      pigs was observed a slow absorption phase was followed by long-lasting levels of
      this inhibitor. C(max) and AUC((0-24)) showed dose-dependent increases, while
      elimination half-life and t(max) value did not change significantly with dose. In
      contrast, saline-dissolved argatroban showed a faster absorption phase followed
      by a shorter elimination half-life. Argatroban dissolved in sorbitol/ethanol
      leads to long-lasting plasma levels due to the formation and permanent
      dissolution of a crystalline depot at the injection place. This represents a
      simple way to deliver argatroban continuously over an extended period which can
      be beneficial for prophylaxis or treatment of chronic coagulations disorders.

PMID- 22988499
TI  - RGD-Dependent Epithelial Cell-Matrix Interactions in the Human Intestinal Crypt.
AB  - Interactions between the extracellular matrix (ECM) and integrin receptors
      trigger structural and functional bonds between the cell microenvironment and the
      cytoskeleton. Such connections are essential for adhesion structure integrity and
      are key players in regulating transduction of specific intracellular signals,
      which in turn regulate the organization of the cell microenvironment and,
      consequently, cell function. The RGD peptide-dependent integrins represent a key
      subgroup of ECM receptors involved in the maintenance of epithelial homeostasis.
      Here we review recent findings on RGD-dependent ECM-integrin interactions and
      their roles in human intestinal epithelial crypt cells.

PMID- 22988501
TI  - The effects of gas humidification with high-flow nasal cannula on cultured human
      airway epithelial cells.
AB  - Humidification of inspired gas is important for patients receiving respiratory
      support. High-flow nasal cannula (HFNC) effectively provides temperature and
      humidity-controlled gas to the airway. We hypothesized that various levels of gas
      humidification would have differential effects on airway epithelial monolayers.
      Calu-3 monolayers were placed in environmental chambers at 37 degrees C with
      relative humidity (RH) < 20% (dry), 69% (noninterventional comparator), and >90%
      (HFNC) for 4 and 8 hours with 10 L/min of room air. At 4 and 8 hours, cell
      viability and transepithelial resistance measurements were performed, apical
      surface fluid was collected and assayed for indices of cell inflammation and
      function, and cells were harvested for histology (n = 6/condition).
      Transepithelial resistance and cell viability decreased over time (P < 0.001)
      between HFNC and dry groups (P < 0.001). Total protein secretion increased at 8
      hours in the dry group (P < 0.001). Secretion of interleukin (IL)-6 and IL-8 in
      the dry group was greater than the other groups at 8 hours (P < 0.001).
      Histological analysis showed increasing injury over time for the dry group. These
      data demonstrate that exposure to low humidity results in reduced epithelial cell
      function and increased inflammation.

PMID- 22988502
TI  - Cigarette and waterpipe smoking decrease respiratory quality of life in adults:
      results from a national cross-sectional study.
AB  - Background. Chronic obstructive pulmonary disease (COPD) is gaining an importance
      over the world, and its effect on quality of life is better grasped. Our
      objective was to use the Clinical COPD Questionnaire (CCQ) to describe the
      respiratory quality of life in the Lebanese population, stressing on differences
      between smokers and nonsmokers. Methods. Using data from a cross-sectional
      national study, we checked the construct validity and reliability of the CCQ.
      Factors and items correlation with postbronchodilator FEV1/FVC were reported, in
      addition to factors and scale association with COPD and its severity. We then
      conducted a multiple regression to find predictors of quality of life. Results.
      The CCQ demonstrated excellent psychometric properties, with adequacy to the
      sample and high consistency. Smokers had a decreased respiratory quality of life
      versus nonsmokers, independently of their respiratory disease status and
      severity. This finding was confirmed in COPD individuals, where several
      environmental factors, lower education, and cumulative smoking of cigarette and
      of waterpipe were found to be independent predictors of a lower quality of life,
      after adjusting for COPD severity. Conclusions. Smoking decreases the respiratory
      quality of life of Lebanese adults; this issue has to be further emphasized
      during smoking cessation and patients' education.

PMID- 22988500
TI  - Involvement of Src in the Adaptation of Cancer Cells under Microenvironmental
      Stresses.
AB  - Protein-tyrosine phosphorylation, which is catalyzed by protein-tyrosine kinase
      (PTK), plays a pivotal role in a variety of cellular functions related to health
      and disease. The discovery of the viral oncogene Src (v-Src) and its cellular
      nontransforming counterpart (c-Src), as the first example of PTK, has opened a
      window to study the relationship between protein-tyrosine phosphorylation and the
      biology and medicine of cancer. In this paper, we focus on the roles played by
      Src and other PTKs in cancer cell-specific behavior, that is, evasion of
      apoptosis or cell death under stressful extracellular and/or intracellular
      microenvironments (i.e., hypoxia, anoikis, hypoglycemia, and serum deprivation).

PMID- 22988503
TI  - Autism: where genetics meets the immune system.

PMID- 22988504
TI  - Retrospective analysis of metabolic syndrome: prevalence and distribution in
      executive population in urban pakistan.
AB  - Background. Metabolic Syndrome (MetS) is a major public health concern.
      Objective. The aim of this study was to estimate the frequency of MetS, its
      components, and factors associated with MetS amongst apparently healthy
      individuals in Pakistan. Methods. A retrospective cross-sectional study was
      conducted at the executive Clinics of Aga Khan Hospital, Pakistan. Medical
      records of patients aged >=18 years visiting the clinics from July 2011 to
      December 2011 were consecutively reviewed. Records in which either MetS
      components data or 10% of overall data was missing were excluded. A total of 1329
      participants' records was included in final analysis. Data was analyzed using
      SPSS version 19 and multivariable logistic regression was used to identify the
      factors associated with MetS. Results. A total of 847 (63.7%) participants had
      MetS; mean age of the participants were 47.6 +/- 11.6 years. About 70.4% were
      males and 29.6% were females. Approximately 70% of participants had BMI >=25
      kg/m(2). MetS was associated with male gender (AOR = 2.1; 95% C.I: 1.6-3.2) and
      history of diabetes among parents (AOR = 3.0; 95% C.I: 1.6-6.0). Conclusion. This
      study shows that a large proportion of population has MetS and is overweight or
      obese. This requires urgent interventions on part of health care providers'
      especially family physicians. Educating masses about life style factors can make
      a difference. Further researches on this issue are warranted.

PMID- 22988506
TI  - SELDI-TOF-MS Serum Profiling Reveals Predictors of Cardiac MRI Changes in
      Marathon Runners.
AB  - Purpose. To utilize proteomics to discover proteins associated with significant
      cardiac magnetic resonance imaging (MRI) changes in marathon runners. Methods.
      Serum from 25 runners was analyzed by surface enhanced laser desorption
      ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Proteomic profiles
      were compared in serum samples obtained prior to the race, at the finish line and
      within 7 hours after race to identify dynamic proteins correlated with cardiac
      MRI changes. Results. 693 protein/peptide clusters were identified using two
      ProteinChip surface chemistries and, of these, 116 were significantly different
      between the three time points. We identified 7 different patterns of protein
      expression change within the runners and 5 prerace protein peaks, 16 finish-line
      protein levels, and 15 postrace proteins which were correlated with significant
      postrace cardiac MRI changes. Conclusions. This study has identified baseline
      levels of proteins which may be predictive of risk of significant cardiac damage
      following a marathon race. Preliminary identification of the significant proteins
      suggested the involvement of cytokines and other proteins involved in stress and
      inflammatory response.

PMID- 22988505
TI  - Weight gain, schizophrenia and antipsychotics: new findings from animal model and
      pharmacogenomic studies.
AB  - Excess body weight is one of the most common physical health problems among
      patients with schizophrenia that increases the risk for many medical problems,
      including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and
      hypertension, and accounts in part for 20% shorter life expectancy than in
      general population. Among patients with severe mental illness, obesity can be
      attributed to an unhealthy lifestyle, personal genetic profile, as well as the
      effects of psychotropic medications, above all antipsychotic drugs. Novel
      "atypical" antipsychotic drugs represent a substantial improvement on older
      "typical" drugs. However, clinical experience has shown that some, but not all,
      of these drugs can induce substantial weight gain. Animal models of antipsychotic
      related weight gain and animal transgenic models of knockout or overexpressed
      genes of antipsychotic receptors have been largely evaluated by scientific
      community for changes in obesity-related gene expression or phenotypes. Moreover,
      pharmacogenomic approaches have allowed to detect more than 300 possible
      candidate genes for antipsychotics-induced body weight gain. In this paper, we
      summarize current thinking on: (1) the role of polymorphisms in several candidate
      genes, (2) the possible roles of various neurotransmitters and neuropeptides in
      this adverse drug reaction, and (3) the state of development of animal models in
      this matter. We also outline major areas for future research.

PMID- 22988507
TI  - Resistance training and older adults with type 2 diabetes mellitus: strength of
      the evidence.
AB  - Objective. This paper analyzes the effects of resistance training (RT) on
      metabolic, neuromuscular, and cardiovascular functions in older adults (mean age
      >= 65 years) with type 2 diabetes (T2DM). Research Design and Methods. A
      systematic review conducted by two reviewers of the published literature produced
      3 records based on 2 randomized controlled trials that assessed the effect of RT
      on disease process measures and musculoskeletal/body composition measures.
      Statistical, Comprehensive Meta-Analysis (version 2) software was used to compute
      Hedge's g, and results were calculated using the random effects model to account
      for methodological differences amongst studies. Results. Largest effect of RT was
      seen on muscle strength; especially lower body strength, while the point estimate
      effect on body composition was small and not statistically significant. The
      cumulative point estimate for the T2DM disease process measures was moderate and
      statistically significant. Conclusions. RT generally had a positive effect on
      musculoskeletal, body composition, and T2DM disease processes measures, with
      tentative conclusions based on a low number of completed RCTs. Thus, more
      research is needed on such programs for older adults (>=65 years) with T2DM.

PMID- 22988509
TI  - The de morton mobility index: normative data for a clinically useful mobility
      instrument.
AB  - Determining mobility status is an important component of any health assessment
      for older adults. In order for a mobility measure to be relevant and meaningful,
      normative data are required for comparison to a healthy reference population. The
      DEMMI is the first mobility instrument to measure mobility across the spectrum
      from bed bound to functional levels of independent mobility. In this cross
      sectional observational study, normative data were obtained for the DEMMI from a
      population of 183 healthy, community-dwelling adults age 60+ who resided in
      Vancouver, Canada and Melbourne, Australia. Older age categories had
      significantly lower DEMMI mobility mean scores (P < 0.05), as did individuals who
      walked with a mobility aid or lived in semi-independent living (assisted living
      or retirement village), whereas DEMMI scores did not differ by sex (P = 0.49) or
      reported falls history (P = 0.21). Normative data for the DEMMI mobility
      instrument provides vital reference scores to facilitate its use across the
      mobility spectrum in clinical, research, and policymaking settings.

PMID- 22988508
TI  - The role of lifestyle behaviors on 20-year cognitive decline.
AB  - This study examined the association between smoking, physical activity and
      dietary choice at 36 and 43 years, and change in these lifestyle behaviors
      between these ages, and decline in verbal memory and visual search speed between
      43 and 60-64 years in 1018 participants from MRC National Survey of Health and
      Development (NSHD, the British 1946 birth cohort). ANCOVA models were adjusted
      for sex, social class of origin, childhood cognition, educational attainment,
      adult social class, and depression; then the lifestyle behaviors were
      additionally mutually adjusted. Results showed that healthy dietary choice and
      physical activity were associated, respectively, with slower memory and visual
      search speed decline over 20 years, with evidence that increasing physical
      activity was important. Adopting positive health behaviors from early midlife may
      be beneficial in reducing the rate of cognitive decline and ultimately reducing
      the risk of dementia.

PMID- 22988510
TI  - Social Networks and Memory over 15 Years of Followup in a Cohort of Older
      Australians: Results from the Australian Longitudinal Study of Ageing.
AB  - The purpose was to examine the relationship between different types of social
      networks and memory over 15 years of followup in a large cohort of older
      Australians who were cognitively intact at study baseline. Our specific aims were
      to investigate whether social networks were associated with memory, determine if
      different types of social networks had different relationships with memory, and
      examine if changes in memory over time differed according to types of social
      networks. We used five waves of data from the Australian Longitudinal Study of
      Ageing, and followed 706 participants with an average age of 78.6 years (SD 5.7)
      at baseline. The relationships between five types of social networks and changes
      in memory were assessed. The results suggested a gradient of effect; participants
      in the upper tertile of friends or overall social networks had better memory
      scores than those in the mid tertile, who in turn had better memory scores than
      participants in the lower tertile. There was evidence of a linear, but not
      quadratic, effect of time on memory, and an interaction between friends' social
      networks and time was apparent. Findings are discussed with respect to mechanisms
      that might explain the observed relationships between social networks and memory.

PMID- 22988511
TI  - Barriers are not the limiting factor to participation in physical activity in
      canadian seniors.
AB  - The identification of barriers to physical activity and exercise has been used
      for many decades to explain exercise behavior in older adults. Typically health
      concerns are the number one barrier to participation. Data from CCHS-HA dataset
      (N = 20, 875) were used to generate a sample of Canadians, 60+ years, who did not
      identify a health condition limitation, illness, or injury as a barrier to
      participation in physical activity (n = 4,900) making this dataset unique in
      terms of the study of barriers to participation. While the vast majority of older
      adults participated in physical activity, 9.4% did not. The relationships between
      nonparticipation, barriers, self-reported health status, and chronic health
      conditions were determined using binary logistic regression. The main findings
      suggest that traditional barriers and self-reported health status are not
      responsible for nonparticipation. Nonparticipation was best predicted by chronic
      health conditions suggesting a disconnect between self-reported health status and
      underlying health conditions. The data are clear in suggesting that barriers are
      not the limiting factor and physical activity programming must be focused on
      meeting the health needs of our aging population.

PMID- 22988513
TI  - Hepatic Metabolic, Inflammatory, and Stress-Related Gene Expression in Growing
      Mice Consuming a Low Dose of Trans-10, cis-12-Conjugated Linoleic Acid.
AB  - Dietary trans-10, cis-12-conjugated linoleic acid (trans-10, cis-12-CLA) fed to
      obese and nonobese rodents reduces body fat but leads to greater liver mass due
      to steatosis. The molecular mechanisms accompanying such responses remain largely
      unknown. Our study investigated the effects of chronic low trans-10, cis-12-CLA
      supplementation on hepatic expression of 39 genes related to metabolism,
      inflammation, and stress in growing mice. Feeding a diet supplemented with 0.3%
      trans-10, cis-12-CLA (wt/wt basis) for 6 weeks increased liver mass and
      concentration of long-chain fatty acids (LCFAs) in liver, while adipose tissue
      mass decreased markedly. These changes were accompanied by greater expression of
      genes involved in LCFA uptake (Cd36), lipogenesis, and triacylglycerol synthesis
      (Acaca, Gpam, Scd, Pck1, Plin2). Expression of these genes was in line with
      upregulation of the lipogenic transcription factor Srebf1. Unlike previous
      studies where higher >0.50% of the diet) doses of trans-10, cis-12-CLA were fed,
      we found greater expression of genes associated with VLDL assembly/secretion
      (Mttp, Cideb), ketogenesis (Hmgcs2, Bdh1), and LCFA oxidation (Acox1, Pdk4) in
      response to trans-10, cis-12-CLA. Dietary CLA, however, did not affect
      inflammation- and stress-related genes. Results suggested that a chronic low dose
      of dietary CLA increases liver mass and lipid accumulation due to activation of
      lipogenesis and insufficient induction of LCFA oxidation and VLDL
      assembly/secretion.

PMID- 22988514
TI  - Bacteria isolations from broiler and layer chicks in zambia.
AB  - Chick mortality (CM) is one of the major constraints to the expansion of the
      poultry industry in Zambia. Of the 2,829 avian disease cases submitted to the
      national diagnostic laboratory based at the Central Veterinary Research Institute
      in Lusaka between 1995 and 2007, 34.39% (973/2,829) were from CM cases. The
      disease accounted for 40.2% (218,787/544,903) mortality in the affected flocks
      with 89.6% (196,112/218,787) of the affected birds dying within seven days. Major
      bacteria species involved were Escherichia coli, Salmonella gallinarum, and
      Proteus species being isolated from 84.58%, 46.15%, and 26.93% of the reported CM
      cases (n = 973), respectively. Detection of Salmonella typhimurium, Salmonella
      enteritidis, and Salmonella dublin indicates that poultry has the potential of
      transmitting zoonotic pathogenic bacteria to humans. The proportion of Salmonella
      gallinarum reactors in the adult breeding stock was generally low (<0.5%)
      throughout the study period although its prevalence in CM cases was correlated (r
      = 0.68, P < 0.011) with seroprevalence of the same pathogen in the adult breeding
      stock. Given that the disease accounts for a large proportion of the avian
      diseases in Zambia as shown in the present study (34.39%, n = 2,829), it is
      imperative that an effective disease control strategy aimed at reducing its
      occurrence should be developed.

PMID- 22988512
TI  - Ubiquitin-mediated regulation of endocytosis by proteins of the arrestin family.
AB  - In metazoans, proteins of the arrestin family are key players of G-protein
      coupled receptors (GPCRS) signaling and trafficking. Following stimulation,
      activated receptors are phosphorylated, thus allowing the binding of arrestins
      and hence an "arrest" of receptor signaling. Arrestins act by uncoupling
      receptors from G proteins and contribute to the recruitment of endocytic
      proteins, such as clathrin, to direct receptor trafficking into the endocytic
      pathway. Arrestins also serve as adaptor proteins by promoting the recruitment of
      ubiquitin ligases and participate in the agonist-induced ubiquitylation of
      receptors, known to have impact on their subcellular localization and stability.
      Recently, the arrestin family has expanded following the discovery of arrestin
      related proteins in other eukaryotes such as yeasts or fungi. Surprisingly, most
      of these proteins are also involved in the ubiquitylation and endocytosis of
      plasma membrane proteins, thus suggesting that the role of arrestins as ubiquitin
      ligase adaptors is at the core of these proteins' functions. Importantly,
      arrestins are themselves ubiquitylated, and this modification is crucial for
      their function. In this paper, we discuss recent data on the intricate
      connections between arrestins and the ubiquitin pathway in the control of
      endocytosis.

PMID- 22988515
TI  - Prognostic significance of tissue inhibitor of metalloproteinase-1 in breast
      cancer.
AB  - Introduction. Despite advances in breast cancer systemic treatment, new
      prognostic and predictive factors are still needed. Tissue inhibitor of
      metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix
      metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role
      of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic
      significance of TIMP-1 in breast cancer. Methods. A single center-based case
      control study was applied. Primary breast cancers from women with early stage
      disease treated with standard adjuvant therapy were analyzed by gene expression
      microarrays and immunohistochemistry for TIMP-1. Results. At the optimized cut
      point, patients with high TIMP-1 RNA levels had a significantly shorter time to
      relapse, with a hazard ratio (HR) of 1.64 (P = 0.04), but without significant
      differences in overall survival (HR 1.29, P = 0.37). Although cytoplasmic
      overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0, P
      = 0.92), there was a tendency for short overall survival in patients with high
      expression (HR 1.41, P = 0.21). Conclusions. Our data indicate that elevated TIMP
      1 RNA levels are independently prognostic for early recurrence, and there is a
      tendency for association of high cytoplasmic TIMP-1 protein levels with short
      survival in primary breast cancer.

PMID- 22988516
TI  - The effect of accompanying in situ ductal carcinoma on accuracy of measuring
      malignant breast tumor size using B-mode ultrasonography and real-time
      sonoelastography.
AB  - Objectives. Clinical estimation of malignant breast tumor size is critical for
      preoperative planning and is crucial for following up the tumor's response to the
      therapy in case she receives a neoadjuvant chemotharapy. Ductal carcinoma in situ
      (DCIS) accompanies about 25.4% of detected invasive breast cancers. The aim of
      this study was to examine the effect of the presence of DCIS on the accuracy of
      the ultrasonographic measuring malignant breast tumor size using B-mode and real
      time elastography. Materials and Methods. We recruited histologically confirmed
      breast cancer patients in a prospective observational study. Results. We
      recruited 50 breast cancer patients with a median age of 57.5 years. DCIS was
      confirmed to accompany 42% (n = 21) of the cases. Tumor size estimation using B
      mode sonography (P < 0.001) as well as using real time elastography (P < 0.001).
      was statistically significant correlated to the actual tumor size. Presence of
      DCIS in 42% of our recruited patients affected the tumor size estimation using
      both methods thus losing the correlation between both estimations (P = 0.794).
      Conclusion. This study shows that the presence of DCIS significantly affects the
      accuracy of measuring the sizes of malignant breast tumors when using either B
      mode ultrasonography or real time elastography.

PMID- 22988517
TI  - The utility of scoring systems in predicting early and late mortality in
      alcoholic hepatitis: whose score is it anyway?
AB  - Background. Alcoholic hepatitis (AH) is a distinct clinical entity in the
      spectrum of alcoholic liver disease with a high short-term mortality. Several
      scoring systems are being used to assess the severity of AH but the ability of
      these scores to predict long-term survival in these patients is largely unknown.
      Aims. We aim to assess the utility of five different scoring systems Child Pugh
      (CP), model for end-stage liver disease (MELD), Maddrey's discriminant function
      (mDF), Glasgow AH score (GAHS), and age-bilirubin-INR-creatinine (ABIC) score in
      predicting shot-term and long-term survival in patients with AH. Methods.
      Patients with histological evidence of AH were identified from our database. The
      clinical and biochemical parameters were used to calculate the 5 different
      scores. The prognostic utility of these scores was determined by generating an
      ROC curve for survival at 30 days, 90 days, 6 months, and 1 year. Results and
      Conclusions. All 5 scores with the exception of CP score have a similar accuracy
      in predicting the short-term prognosis. However, they are uniformly poor in
      predicting longer-term survival with AUROC not exceeding 0.74. CP score is a very
      poor predictor of survival in both short and long term. Abstinence from alcohol
      was significantly (P < 0.05) associated with survival at 1 year.

PMID- 22988518
TI  - Primary sclerosing cholangitis associated with elevated immunoglobulin-g4: a
      preliminary study.
AB  - Background. Immunoglobulin IgG4-associated cholangitis (IAC) disease is a
      systemic disease histologically characterized by extensive T lymphocytes and IgG4
      positive plasma cell infiltration in various organs. Prevalence of IAC in PSC
      patients was reported to be between 7% and 11.6% in a few previous studies. This
      study was carried out to evaluate frequency of serum IgG4 level in PSC patient
      referred to the gastroenterology ward of Taleghani educational hospital in
      Tehran, Iran. Material and Methods. This study was a prospective analytical cross
      sectional study. Clinical presentation, laboratory values, imaging changes,
      inflammatory bowel disease (IBD), esophageal varices, ascites, and child score in
      newly PSC patients with elevated IgG4 were determined and compared with PSC
      patients with normal levels of IgG4. Data was analyzed by using SPSS software.
      The frequency and standard deviations were calculated. Differences among groups
      were evaluated by using the chi-square, fisher exact, and Mann-Whitney U tests.
      Results. 34 patients with PSC were examined in the study period, of which 9 cases
      (26.5%) had high IgG4 levels. Most of the patients were male, 23 cases (67.6%)
      and nonsmoker, 26 cases (76.5%). Patient average age was 47 years old (range 21
      67 years). There was not any significant relationship among patients with IAC and
      PSC patients in terms of variables such as age, smoking, presence of IBD,
      ascites, esophageal varices, child score, and imaging findings (P > 0.05).
      Conclusion. IAC should be suspected in cases of unexplained biliary strictures
      with increased serum IgG4. Testing PSC patients for IgG4 and treating those who
      have high levels with corticosteroids in clinical trials should be considered in
      future studies.

PMID- 22988519
TI  - Preventing Microbial Contamination during Long-Term In Vitro Culture of Human
      Granulosa-Lutein Cells: An Ultrastructural Analysis.
AB  - Purpose. To investigate whether the addition of antibiotic/antimycotic during
      human granulosa-lutein cells (GLCs) isolation and cell-plating procedures
      prevents microbial contamination after 144 h of culture and also evaluate the
      effects of contamination on GLCs ultrastructure and steroid secretion. Methods.
      GLCs obtained from five women submitted to assisted reproductive techniques
      (ARTs) were isolated with PBS supplemented with antibiotic/antimycotic or PBS
      nonsupplemented and cultured for 144 h. GLCs were evaluated by transmission
      electron microscopy (TEM), and estradiol (E2) and progesterone (P4) secretion was
      assayed by chemiluminescence. Results. Although no contaminating microorganisms
      were identified by light microscopy, TEM analyses revealed several bacterial
      colonies in culture dishes of GLCs isolated with only PBS. Bacterial
      contamination disrupted the adherence of the GLCs to the culture plate
      interfering with monolayer formation affecting the growth pattern of GLCs.
      Various cellular debris and bacteria were observed, and no organelles were found
      in the cytoplasm of infected cells. While bacterial contamination decreased
      estradiol media levels, it increased progesterone, as compared with
      noncontaminated group. Conclusion. Taken together, our data showed that the
      addition of a high dose of antibiotic/antimycotic during the isolation and cell
      plating procedures prevents microbial contamination of long-term GLCs culture as
      its effects on cells growth and function in vitro.

PMID- 22988520
TI  - A Comparative Study of Relationship between Micronutrients and Gestational
      Diabetes.
AB  - In this paper, we studied the relation between the micronutrient and gestational
      diabetes. Therefore, we measured micronutrient concentration including Ni, Al,
      Cr, Mg, Fe, Zn, Cu, and Se in serum of women with gestational diabetes between 24
      and 28 weeks of gestational age (study group) who had inclusion criteria and
      comparison with micronutrient levels in normal pregnant women with same
      gestational age (control group). Results showed that there was no significant
      difference between the serum micronutrient level (Ni, Al, Cr, Mg, Zn, Cu, Se) in
      study and control groups except serum level of iron which in serum of gestational
      diabetic women was lower than normal pregnant women and difference was
      significant.

PMID- 22988521
TI  - High-fat programming of hyperglycemia, hyperinsulinemia, insulin resistance,
      hyperleptinemia, and altered islet architecture in 3-month-old wistar rats.
AB  - High-fat programming, by exposure to a high-saturated-fat diet in utero and/or
      during lactation, compromises beta-cell development and function in neonatal and
      weanling offspring. Therefore, high-fat programming effects were investigated on
      metabolism and islet architecture in young adult rats. Three-month-old male and
      female Wistar rat offspring were studied: HFG (maintained on a high-fat diet
      throughout fetal life), HFP (high-fat diet maintenance from birth to 3 months),
      and HFGP (high-fat diet maintenance throughout fetal and postnatal life). Control
      rats were maintained on a standard laboratory diet. Pancreata were double
      immunolabeled for insulin and glucagon to assess islet morphology and with Ki-67
      to determine islet and acinar cell proliferation. HFP and HFGP males were
      heavier, hyperleptinemic, and hyperinsulinemic. Hyperglycemia presented in HFP
      males, HFP females, and HFGP males. HFGP males and HFP females were insulin
      resistant. HFP males displayed beta- and alpha-cell hyperplasia with alpha-cell
      hypertrophy evident in HFP females. Acinar cell proliferation rates were
      increased in HFP males. Postnatal high-fat programming induced the most
      diabetogenic phenotype with high-fat maintenance throughout fetal and postnatal
      life resulting in a severely obese phenotype. Fetal and postnatal nutrition
      shapes offspring health outcomes.

PMID- 22988523
TI  - The effect of tempol administration on the aortic contractile responses in rat
      preeclampsia model.
AB  - It is reported that reactive oxygen species production has a critical role in the
      manifestations and complications of preeclampsia. In the present study, the
      effect of tempol on the response changes of aortic rings of preeclamptic rats has
      been studied. Preeclamptic rats (induced by L-NAME) were treated with three
      different oral doses of tempol (20, 60 and 180 mg/kg/day) from the Day 10 of
      gestation. Systolic blood pressure, plasma malondialdehyde and 8-isoprostane and
      the vascular effects of phenylephrine, calcium, acetylcholine and diazoxide were
      the studied parameters. L-NAME administration resulted in hypertension,
      proteinuria, increased oxidative stress markers, increased vascular sensitivity
      to phenylephrine and decreased sensitivity to acetylcholine in pregnant rats. No
      significant changes in response to calcium and diazoxide were observed. Tempol at
      doses of 20 and 60 mg/kg/day significantly reversed these changes but at a high
      dose (180 mg/kg/day), it had no significant effect and in some cases intensified
      the effect. These results revealed that in the experimental preeclampsia, the
      sensitivity of rat aorta to alpha- adrenergic receptor agonists was increased and
      its endothelium-dependent relaxation was decreased. Tempol at lower used doses
      reduced the blood pressure and oxidative stress and restored the normal
      responsiveness of vascular tissue in preeclamptic rats.

PMID- 22988522
TI  - Cow's Milk Allergy Is a Major Contributor in Recurrent Perianal Dermatitis of
      Infants.
AB  - Background. Recurrent perianal inflammation has great etiologic diversity. A
      possible cause is cow's milk allergy (CMA). The aim was to assess the magnitude
      of this cause. Subjects and Methods. This follow up clinical study was carried
      out on 63 infants with perianal dermatitis of more than 3 weeks with history of
      recurrence. Definitive diagnosis was made for each infant through medical history
      taking, clinical examination and investigations including stool analysis and
      culture, stool pH and reducing substances, perianal swab for different cultures
      and staining for Candida albicans. Complete blood count and quantitative
      determination of cow's milk-specific serum IgE concentration were done for all
      patients. CMA was confirmed through an open withdrawal-rechallenge procedure.
      Serum immunoglobulins and CD markers as well as gastrointestinal endoscopies were
      done for some patients. Results. Causes of perianal dermatitis included CMA
      (47.6%), bacterial dermatitis (17.46%), moniliasis (15.87%), enterobiasis (9.52%)
      and lactose intolerance (9.5%). Predictors of CMA included presence of bloody
      and/or mucoid stool, other atopic manifestations, anal fissures, or recurrent
      vomiting. Conclusion. We can conclude that cow's milk allergy is a common cause
      of recurrent perianal dermatitis. Mucoid or bloody stool, anal fissures or
      ulcers, vomiting and atopic manifestations can predict this etiology.

PMID- 22988524
TI  - Nursing student perceptions of reflective journaling: a conjoint value analysis.
AB  - This study used a statistical technique, conjoint value analysis, to determine
      student perceptions related to the importance of predetermined reflective
      journaling attributes. An expert Delphi panel determined these attributes and
      integrated them into a survey which presented students with multiple journaling
      experiences from which they had to choose. After obtaining IRB approval, a
      convenience sample of 66 baccalaureate nursing students completed the survey. The
      relative importance of the attributes varied from a low of 16.75% (format) to a
      high of 23.58% (time). The model explained 77% of the variability of student
      journaling preferences (r(2) = 0.77). Students preferred shorter time, complete
      confidentiality, one-time complete feedback, semistructured format, and behavior
      recognition. Students with more experience had a much greater preference for a
      free-form format (P < .05) when compared to students with less journaling
      experience. Additionally, the results of English as a second language students
      were significantly different from the rest of the sample. In order to better
      serve them, educators must consider the relative importance of these attributes
      when developing journaling experiences for their students.

PMID- 22988525
TI  - Radiation Dose Reduction during Radial Cardiac Catheterization: Evaluation of a
      Dedicated Radial Angiography Absorption Shielding Drape.
AB  - Objectives. Radiation scatter protection shield drapes have been designed with
      the goal of decreasing radiation dose to the operators during transfemoral
      catheterization. We sought to investigate the impact on operator radiation
      exposure of various shielding drapes specifically designed for the radial
      approach. Background. Radial access for cardiac catheterization has increased due
      to improved patient comfort and decreased bleeding complications. There are
      concerns for increased radiation exposure to patients and operators. Methods.
      Radiation doses to a simulated operator were measured with a RadCal Dosimeter in
      the cardiac catheterization laboratory. The mock patient was a 97.5 kg fission
      product phantom. Three lead-free drape designs were studied. The drapes were
      placed just proximal to the right wrist and extended medially to phantom's trunk.
      Simulated diagnostic coronary angiography included 6 minutes of fluoroscopy time
      and 32 seconds of cineangiography time at 4 standard angulated views (8 s each),
      both 15 frames/s. ANOVA with Bonferroni correction was used for statistical
      analysis. Results. All drape designs led to substantial reductions in operator
      radiation exposure compared to control (P < 0.0001). The greatest decrease in
      radiation exposure (72%) was with the L-shaped design. Conclusions. Dedicated
      radial shielding drapes decrease radiation exposure to the operator by up to 72%
      during simulated cardiac catheterization.

PMID- 22988526
TI  - Primary gastric lymphoma: conservative treatment modality is not inferior to
      surgery for early-stage disease.
AB  - Objectives. The aim of this study was to evaluate clinical characteristics,
      prognostic factors, survival rates, and treatment modalities in patients with
      primary gastric lymphoma (PGL). Methods. We retrospectively reviewed and analyzed
      data from patients treated for PGL in our clinic from 1998 through 2010. Staging
      was performed using the Lugano Staging System. Overall and disease-free survival
      (OS and DFS) were calculated from the date of diagnosis. Results. We identified
      79 patients. Thirty-seven patients (47%) were male. The median age at
      presentation was 57 (18-85) years. The median follow-up time was 41 (9-52)
      months. Thirty patients (38%) underwent surgery, 74 (92%) received chemotherapy,
      and 18 (23%) received radiotherapy. The five-year OS and DFS rates were 91.2% and
      83.9%, respectively, in patients with stage I/II or IIE disease and 70.6% and
      65.5%, respectively, in patients with stage IV disease (P = 0.02 for both rates).
      Treatment modality (surgical or conservative) had no impact on OS or DFS in early
      stages. In a multivariate analysis, poor performance status, advanced stage, and
      high LDH levels were significant bad prognostic factors for DFS, while advanced
      stage, poor performance status, and age > 60 years were significant bad
      prognostic factors for OS. Conclusion. Surgery provides no advantage for survival
      over conservative treatment; thus, conservative treatment modalities should be
      preferred initially at early stages of PGL.

PMID- 22988527
TI  - Response surface optimization of sustained release metformin-hydrochloride matrix
      tablets: influence of some hydrophillic polymers on the release.
AB  - The aim of the present work was designed to develop a model-sustained release
      matrix tablet formulation for Metformin hydrochloride using wet granulation
      technique. In the present study the formulation design was employed to
      statistically optimize different parameters of Metformin hydrochloride tablets at
      different drug-to-polymer ratios employing polymers Hydroxypropyl methylcellulose
      of two grades K4M and K100M as two independent variables whereas the dependent
      variables studied were X(60), X(120), T(50), T(90), n, and b values obtained from
      dissolution kinetics data. The in vitro drug release studies were carried out at
      simulated intestinal fluids, and the release showed a non-Fickian anomalous
      transport mechanism. The drug release was found to reveal zero order kinetics.
      The granules and the tablets were tested for their normal physical,
      morphological, and analytical parameters and were found to be within the
      satisfactory levels. There were no significant drug-polymer interactions as
      revealed by infrared spectra. It has been found out that on an optimum increased
      Hydroxypropyl methylcellulose K100M concentration and decreased Hydroxypropyl
      methylcellulose K4M concentration the formulations were elegant in terms of their
      release profiles and were found to be statistically significant and generable.

PMID- 22988528
TI  - Use of zirconia to restore severely worn dentition: a case report.
AB  - The management of tooth wear has been a subject of increasing interest from both
      preventive and restorative points of view. Severe tooth wear is frequently
      multifactorial and variable. Successful management is a subject of interest in
      dentistry. A critical aspect is to determine the occlusal vertical dimension
      (OVD) and a systematic approach that can lead to a predictable and favorable
      treatment prognosis. Management of patients with worn dentition is complex and
      difficult. Accurate clinical and radiographic examinations, a diagnostic wax-up,
      and determining OVD are crucial. This paper describes the full-mouth
      rehabilitation of a 47-year-old bruxer with a severely worn dentition.

PMID- 22988529
TI  - Preoperative embolization reduces the risk of cathecolamines release at the time
      of surgical excision of large pelvic extra-adrenal sympathetic paraganglioma.
AB  - A 30-year-old woman with severe hypertension was admitted to the hospital with a
      history of headache, palpitations, and diaphoresis following sexual intercourse.
      Twenty-four hour urinary excretion of free catecholamines and metabolites was
      markedly increased as was serum chromogranin A. Computed tomography scan revealed
      a large mass in the left adnex site and magnetic resonance imaging confirmed the
      computer tomography finding, suggesting the presence of extra-adrenal sympathetic
      paraganglioma. I-metaiodobenzyl guanidine scintigram revealed an increased uptake
      in the same area. Transcatheter arterial embolization of the mass resulted in
      marked decreases in blood pressure and urinary excretion of free catecholamines
      and metabolites. Surgical excision of the mass was then accomplished without
      complication. Preoperative embolization is a useful and safe procedure which may
      reduce the risk of catecholamines release at the time of surgical excision in
      large pelvic extra-adrenal sympathetic paraganglioma.

PMID- 22988530
TI  - Bilateral primary adrenal lymphoma presenting with adrenal insufficiency.
AB  - Lymphoma may occasionally involve the adrenal glands, but primary adrenal
      lymphoma (PAL) is very rare and only few cases have been reported. We present a
      case of a 60-year-old, otherwise healthy, woman, with bilateral PAL presenting
      with adrenal insufficiency. The patient responded initially upon administration
      of large doses of intravenously hydrocortisone with total remission of symptoms.
      An abdominal computerized tomography scan demonstrated bilateral adrenal lesions
      but did not demonstrate any other pathology. Since metastatic malignant disease
      was suspected a positron-emission-tomography scan was performed only showing
      significant uptake in the adrenal glands. Endocrine evaluation did not reveal
      abnormal function of any hormonal system and the patient was scheduled for
      bilateral adrenalectomy. However the clinical condition deteriorated rapidly and
      the patient was readmitted to hospital before surgery was performed. A new
      computerized tomography scan showed rapid progression of disease with further
      enlargement of the adrenal masses and both pulmonary and hepatic metastasis.
      Needle biopsy was performed but the patient refused further treatment and died
      before a diagnosis was obtained. The immuneohistochemical diagnosis was large B
      cell lymphoma. This case should remind clinicians that PAL may be a cause of
      bilateral adrenal incidentaloma especially if the patient presents with adrenal
      insufficiency.

PMID- 22988531
TI  - The rise of tunnel endoscopic surgery: a case report and literature review.
AB  - There has been booming interest in natural orifice transluminal surgery since it
      was first described. Several techniques first developed for the safe transluminal
      access now derive into independent endoscopic surgical procedures. In this paper,
      we describe a case treated by a novel procedure by submucosal tunnelling
      technique and provide a literature review of the rise of tunnel endoscopic
      surgery.

PMID- 22988532
TI  - Bing and neel syndrome.
AB  - Introduction. We report the case of a Bing and Neel syndrome revealed by an
      isolated left ptosis. Case Report. a 57-year-old man was followed up since
      October 2003 for a typical Waldenstrom's macroglobulinemia. A first complete
      remission was obtained with chlorambucil. In August 2004, he relapsed. A second
      complete remission was obtained with RFC chemotherapy regimen (rituximab,
      fludarabine, and cyclophosphamide). In October 2009, the patient presented with
      an isolated left ptosis revealing a Bing and Neel syndrome. The diagnosis was
      suspected on MRI and confirmed by the detection in the CSF of a monoclonal IgM
      similar to the one found in the plasma. A quite good partial remission has been
      obtained after one course of RDHAP (rituximab, dexamethasone, cytarabine, and
      cisplatin) and 3 courses of RDHOx (rituximab, dexamethasone, cytarabine, and
      oxaliplatin), in addition to ten intrahectal chemotherapy injections. The
      treatment was followed by intensification and autologous stem cell
      transplantation. At D58, the patient died due to a septic shock. Conclusion. BNS
      is a rare and potentially treatable complication of WM. It should be considered
      in patients with neurologic symptoms and a history of WM.

PMID- 22988533
TI  - Severe Anaemia during Late Pregnancy.
AB  - Vitamin B12 deficiency is uncommon in pregnancy, it occurs in 10-28% of
      uncomplicated pregnancies, and is associated with a few complications. We present
      a case report of a 21-year-old patient with severe anaemia during late pregnancy
      caused by vitamin B12 deficiency. At 38 weeks gestation and with a BMI of 48.9, a
      history of rupture of membranes was given but not confirmed. On examination, she
      appeared pale and therefore full blood counts were done. Interestingly her
      haemoglobin (Hb) levels were 3.7 g/dL. Folate and vitamin B12 levels were also
      found to be low, and the diagnosis of anaemia caused by vitamin B12 deficiency
      was made. After treatment with vitamin B12 injections, folic acid and blood
      transfusions, the patient's haemoglobin levels improved from 3.7 g/dL to 10.7
      g/dL. The conclusion is that effective history taking, diagnosis, and management
      can prevent many complications that are usually associated with vitamin B12
      deficiency anaemia.

PMID- 22988534
TI  - Tropheryma whipplei Crystalline Keratopathy: Report of a Case and Updated Review
      of the Literature.
AB  - Purpose. To report a case of Tropheryma whipplei infection with crystalline
      keratopathy and review the recent literature on the presentation, diagnosis, and
      management of Whipple's disease. Methods. Detailed case presentation and
      extensive literature search of Pubmed for all years through February 2012 using
      the following search terms: Whipple's disease, Tropheryma whipplei, corneal
      deposits, crystalline keratopathy, and uveitis. Relevant articles were retrieved
      and analyzed. English abstracts were used for non-English articles. Cross
      referencing was employed and reference lists from selected articles were used to
      identify additional pertinent articles. Results. Diagnosis of Whipple's disease
      remains challenging and untreated infection can result in mortality. Ocular signs
      and symptoms are usually nonspecific, but several independent cases have reported
      the presence of intraocular crystals or crystalline-like deposits. Conclusions.
      The presence of intraocular crystals or crystalline-like deposits may be an
      identifying feature of ocular Whipple's disease.

PMID- 22988535
TI  - Complex form variant of dysembryoplastic neuroepithelial tumor of the cerebellum.
AB  - Dysembryoplastic neuroepithelial tumor (DNT) is a benign neoplasm with typical
      supratentorial location, but the possibility of these rare tumors can also be
      located in the posterior fossa must be taken into account. We report a 21-year
      old woman that suffered gait instability, headache, and diplopia. On CT-scan, an
      intraparenchymatous cerebellar tumor was disclosed. It was isodense, showing
      light enhancement after contrast administration. On MRI (T1-weighted image) the
      tumor was isointense, showing inhomogeneous hyperintensity after-gadolinium
      administration. On T2-weighted MRI, the tumor was inhomogenously hyperintense. At
      surgery, a solid and hypervascularized tumor was completely removed. Two years
      after surgery, the patient is symptom-free. Pathological study showed coexistence
      of areas of pilocytic astrocytoma with areas in which small rounded
      oligodendrocyte-like cells (OLC), with strong synaptophysin expression were
      identified. These neurocytic areas showed an eosinophilic matrix forming
      microcysts, and cells with aspect of "floating neurons" were occasionally
      identified. A complex form variant of DNT was diagnosed. Our case suggests that
      in presence of a cerebellar tumor with features of pilocytic astrocytoma, the
      possibility of a complex form variant of DNT should be considered.

PMID- 22988536
TI  - Delusional parasitosis in a female treated with mixed amphetamine salts: a case
      report and literature review.
AB  - Objectives. To explore factors underlying the onset of delusional parasitosis; a
      condition in which an individual has a fixed, false belief that he/she is
      infested with insects. Case Description. MJ is a 57-year-old female who presents
      with symptoms of fatigue and AD/HD. Upon treatment with extended release mixed
      amphetamine salts, the patient displayed symptoms of delusional parasitosis.
      After eventual discontinuation of this medication, her delusions resolved.
      Comments. In order to maintain confidentiality, all identifying information was
      removed. To this end, please note that MJ is a fictitious name.

PMID- 22988537
TI  - A case of laparoscopic mesenteric cyst excision.
AB  - The objective of this study is to discuss the presentation, diagnosis, and
      surgical management of a young, healthy patient with a symptomatic mesenteric
      cyst. He had a 5-month history of abdominal pain from this disorder, and the case
      is presented to illustrate the clinical picture and operative management of this
      rare disorder.

PMID- 22988538
TI  - Unusual Appearance of a Pendulated Gastric Tumor: Always Think of GIST.
AB  - Objective. To investigate the clinicopathological characteristics of
      gastrointestinal stromal tumor (GIST) with significant cystic changes and to
      assess the molecular genetic characteristics. Methods. In a 68-year-old man, a
      large abdominal tumoral mass was discovered incidentally. Computed tomography
      (CT) and magnetic resonance imaging (MRI) confirmed the presence of a large
      cystic lesion with multiple contrast-enhancing septae and papillary projections.
      No clear connection with any of the surrounding organs was identified. Malignancy
      could not be excluded, and surgery was indicated. During surgery, the large mass
      was found to be attached by a narrow stalk to the large curvature of the stomach.
      Results. The histological features and immunohistiochemical profile of the tumor
      cells (positivity for CD117 and CD34) were consistent with a gastrointestinal
      stromal tumor with a high risk of progressive disease according to the Fletcher
      classification. Diagnosis was confirmed by mutational analysis; this demonstrated
      mutation in exon 14 of PDGFRA. During the followup of 97 months, the patient had
      a cancer-free survival. Conclusions. This case demonstrates that gastrointestinal
      stromal tumors (GISTs) with extensive cystic degeneration should be considered in
      the differential diagnosis of a cystic abdominal mass.

PMID- 22988539
TI  - Ascending aortic wall cohesion: comparison of bicuspid and tricuspid valves.
AB  - Objectives. Bicuspid aortic valve (AV) represents the most common form of
      congenital AV malformation, which is frequently associated with pathologies of
      the ascending aorta. We compared the mechanical properties of the aortic wall
      between patients with bicuspid and tricuspid AV using a new custom-made device
      mimicking transversal aortic wall shear stress. Methods. Between 03/2010 and
      07/2011, 190 consecutive patients undergoing open aortic valve replacement at our
      institution were prospectively enrolled, presenting either with a bicuspid (group
      1, n = 44) or a tricuspid (group 2, n = 146) AV. Aortic wall specimen were
      examined with the "dissectometer" resulting in nine specific aortic-wall
      parameters derived from tensile strength curves (TSC). Results. Patients with a
      bicuspid AV showed significantly more calcified valves (43.2% versus 15.8%, P <
      0.001), and a significantly thinner aortic wall (2.04 +/- 0.42 mm versus 2.24 +/-
      0.41 mm, P = 0.008). Transesophageal echocardiography diameters (annulus, aortic
      sinuses, and sinotubular junction) were significantly larger in the bicuspid
      group (P = 0.003, P = 0.02, P = 0.01). We found no difference in the aortic wall
      cohesion between both groups as revealed by shear stress testing (P = 0.72, P =
      0.40, P = 0.41). Conclusion. We observed no differences of TSC in patients
      presenting with tricuspid or bicuspid AVs. These results may allow us to assume
      that the morphology of the AV and the pathology of the ascending aorta are
      independent.

PMID- 22988541
TI  - Caspase-mediated truncation of tau potentiates aggregation.
AB  - Caspase-mediated truncation of tau is associated with aggregation. We examined
      the impact of manipulation of caspase activity on intracellular aggregation of a
      mutant form of tau (3PO) that forms spontaneous aggregates. Treatment with the
      caspase inhibitor Z-VAD-fmk reduced both N and C-terminal tau truncation but did
      not significantly reduce aggregation. Treatment with staurosporine, which
      activated caspases, increased C-terminal but not N-terminal truncation and
      enhanced aggregation. These findings suggest that caspase activation is one
      potential route, rather than an obligatory initiation step, in aggregation, and
      that N- and C-terminal truncation contribute differentially to aggregation.

PMID- 22988540
TI  - Myocardial viability: what we knew and what is new.
AB  - Some patients with chronic ischemic left ventricular dysfunction have shown
      significant improvements of contractility with favorable long-term prognosis
      after revascularization. Several imaging techniques are available for the
      assessment of viable myocardium, based on the detection of preserved perfusion,
      preserved glucose metabolism, intact cell membrane and mitochondria, and presence
      of contractile reserve. Nuclear cardiology techniques, dobutamine
      echocardiography and positron emission tomography are used to assess myocardial
      viability. In recent years, new advances have improved methods of detecting
      myocardial viability. This paper summarizes the pathophysiology, methods, and
      impact of detection of myocardial viability, concentrating on recent advances in
      such methods. We reviewed the literature using search engines MIDLINE, SCOUPS,
      and EMBASE from 1988 to February 2012. We used key words: myocardial viability,
      hibernation, stunning, and ischemic cardiomyopathy. Recent studies showed that
      the presence of viable myocardium was associated with a greater likelihood of
      survival in patients with coronary artery disease and LV dysfunction, but the
      assessment of myocardial viability did not identify patients with survival
      benefit from revascularization, as compared with medical therapy alone. This
      topic is still debatable and needs more evidence.

PMID- 22988542
TI  - Serum levels of gelatinase associated lipocalin as indicator of the inflammatory
      status in coronary artery disease.
AB  - Background. Atherosclerosis is a chronic inflammatory disease and the acute
      clinical manifestations represent acute on chronic inflammation. Neutrophil
      gelatinase-associated lipocalin (NGAL) is found in the granules of human
      neutrophils, with many diverse functions. The aim of this study was to evaluate
      the hypothesis that levels NGAL in blood may reflect the inflammatory process in
      various stages of coronary artery disease. Methods. We studied 140 patients, with
      SA 40, UA 35, NSTEMI 40, and STEMI 25, and 20 healthy controls. Serum NGAL was
      measured upon admission and before coronary angiography. Results. Significant
      differences were observed in median serum-NGAL(ng/mL) between patients with SA
      (79.23 (IQR, 37.50-100.32)), when compared with UA (108.00 (68.34-177.59)),
      NSTEMI (166.49 (109.24-247.20)), and STEMI (178.63 (111.18-305.92)) patients and
      controls (50.31 (44.30-69.78)) with significant incremental value from SA to
      STEMI. We observed a positive and significant correlation between serum-NGAL and
      hs-CRP (spearman coefficient rho = 0.685, P < 0.0001) as well as with neutrophil
      counts (r = 0.511, P < 0.0001). Conclusions. In patients with coronary artery
      disease serum levels of NGAL increase and reflect the degree of inflammatory
      process. In patients with acute coronary syndromes, serum levels of NGAL have
      high negative predictive value and reflecting the inflammatory status could show
      the severity of coronary clinical syndrome.

PMID- 22988543
TI  - Adult Onset Still's Disease and Autoinflammation.

PMID- 22988544
TI  - Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and
      Functional Impairments following Permanent Focal Cerebral Ischemia in Rats.
AB  - Studies from a single laboratory have shown that in rodent models of permanent
      stroke, administration of the sulfonylurea glibenclamide (Glib) is highly
      effective in reducing edema, mortality, and lesion volume. The Stroke Therapy
      Academic Industry Roundtable (STAIR) recommends that new acute treatments for
      ischemic stroke to be replicated across different laboratories. Accordingly, we
      examined the effect of low-dose Glib in a permanent suture occlusion model of
      stroke. Male Sprague-Dawley rats underwent permanent middle cerebral artery
      occlusion (pMCAO) followed by an initial intraperitoneal injection of Glib (10
      MUg/kg) and the start of a constant infusion (200 ng/h) via miniosmotic pump at
      the onset of ischemia. Functional deficits were assessed by Neurological Severity
      Score (NSS) and grip-strength meter at 24 and 48 h after pMCAO. Glib-treated rats
      showed a significant reduction in infarct volume, lower NSS, and less hemispheric
      swelling compared to vehicle. Grip strength was decreased significantly in pMCAO
      rats compared to shams and significantly improved by treatment with Glib. Taken
      together, these data indicate that Glib has strong neuroprotective effects
      following ischemic stroke and may warrant further testing in future clinical
      trials for human stroke.

PMID- 22988545
TI  - Diurnal Variation and Spatial Distribution Effects on Sulfur Speciation in
      Aerosol Samples as Assessed by X-Ray Absorption Near-Edge Structure (XANES).
AB  - This paper focuses on providing new results relating to the impacts of Diurnal
      variation, Vertical distribution, and Emission source on sulfur K-edge XANES
      spectrum of aerosol samples. All aerosol samples used in the diurnal variation
      experiment were preserved using anoxic preservation stainless cylinders (APSCs)
      and pressure-controlled glove boxes (PCGBs), which were specially designed to
      prevent oxidation of the sulfur states in PM(10). Further investigation of sulfur
      K-edge XANES spectra revealed that PM(10) samples were dominated by S(VI), even
      when preserved in anoxic conditions. The "Emission source effect" on the sulfur
      oxidation state of PM(10) was examined by comparing sulfur K-edge XANES spectra
      collected from various emission sources in southern Thailand, while "Vertical
      distribution effects" on the sulfur oxidation state of PM(10) were made with
      samples collected from three different altitudes from rooftops of the highest
      buildings in three major cities in Thailand. The analytical results have
      demonstrated that neither "Emission source" nor "Vertical distribution"
      appreciably contribute to the characteristic fingerprint of sulfur K-edge XANES
      spectrum in PM(10).

PMID- 22988547
TI  - [Ablation treatment of hepatocellular carcinoma: current status, pitfalls and
      future implications].

PMID- 22988548
TI  - [Radiofrequency ablation therapy and its strategies in multidisciplinary
      treatment of hepatocellular carcinoma].

PMID- 22988546
TI  - Atypical teratoid rhabdoid tumor: current therapy and future directions.
AB  - Atypical teratoid rhabdoid tumors (ATRTs) are rare central nervous system tumors
      that comprise approximately 1-2% of all pediatric brain tumors; however, in
      patients less than 3 years of age this tumor accounts for up to 20% of cases.
      ATRT is characterized by loss of the long arm of chromosome 22 which results in
      loss of the hSNF5/INI-1 gene. INI1, a member of the SWI/SNF chromatin remodeling
      complex, is important in maintenance of the mitotic spindle and cell cycle
      control. Overall survival in ATRT is poor with median survival around 17 months.
      Radiation is an effective component of therapy but is avoided in patients younger
      than 3 years of age due to long term neurocognitive sequelae. Most long term
      survivors undergo radiation therapy as a part of their upfront or salvage
      therapy, and there is a suggestion that sequencing the radiation earlier in
      therapy may improve outcome. There is no standard curative chemotherapeutic
      regimen, but anecdotal reports advocate the use of intensive therapy with
      alkylating agents, high-dose methotrexate, or therapy that includes high-dose
      chemotherapy with stem cell rescue. Due to the rarity of this tumor and the lack
      of randomized controlled trials it has been challenging to define optimal therapy
      and advance treatment. Recent laboratory investigations have identified aberrant
      function and/or regulation of cyclin D1, aurora kinase, and insulin-like growth
      factor pathways in ATRT. There has been significant interest in identifying and
      testing therapeutic agents that target these pathways.

PMID- 22988549
TI  - [Complications arising from radiofrequency ablation of hepatocellular carcinoma
      and preventative measure].

PMID- 22988550
TI  - [Clinical application of ultrasound guided percutaneous ablation therapy for
      hepatocellular carcinoma].

PMID- 22988551
TI  - [Ablation therapy for super-indication hepatocellular carcinoma].

PMID- 22988552
TI  - In memoriam.  John O. Susac, MD (1940-2012).

PMID- 22988553
TI  - [Clinical features of aplastic: anemia patients with hepatitis B virus infection:
      a case report of 12 patients].

PMID- 22988554
TI  - [Research progress in cell-based therapeutics of liver diseases].

PMID- 22988555
TI  - [The role of Th17 cells in liver diseases].

PMID- 22988556
TI  - [Recent advances in understanding the regulatory mechanism of hepatocyte growth
      factor activation].

PMID- 22988557
TI  - X-space MPI: magnetic nanoparticles for safe medical imaging.
AB  - One quarter of all iodinated contrast X-ray clinical imaging studies are now
      performed on Chronic Kidney Disease (CKD) patients. Unfortunately, the iodine
      contrast agent used in X-ray is often toxic to CKD patients' weak kidneys,
      leading to significant morbidity and mortality. Hence, we are pioneering a new
      medical imaging method, called Magnetic Particle Imaging (MPI), to replace X-ray
      and CT iodinated angiography, especially for CKD patients. MPI uses magnetic
      nanoparticle contrast agents that are much safer than iodine for CKD patients.
      MPI already offers superb contrast and extraordinary sensitivity. The iron oxide
      nanoparticle tracers required for MPI are also used in MRI, and some are already
      approved for human use, but the contrast agents are far more effective at
      illuminating blood vessels when used in the MPI modality. We have recently
      developed a systems theoretic framework for MPI called x-space MPI, which has
      already dramatically improved the speed and robustness of MPI image
      reconstruction. X-space MPI has allowed us to optimize the hardware for fi ve MPI
      scanners. Moreover, x-space MPI provides a powerful framework for optimizing the
      size and magnetic properties of the iron oxide nanoparticle tracers used in MPI.
      Currently MPI nanoparticles have diameters in the 10-20 nanometer range, enabling
      millimeter-scale resolution in small animals. X-space MPI theory predicts that
      larger nanoparticles could enable up to 250 micrometer resolution imaging, which
      would represent a major breakthrough in safe imaging for CKD patients.

PMID- 22988558
TI  - Biologically responsive polymeric nanoparticles for drug delivery.
AB  - Responsive nanoparticles that release their drug cargo in accordance with a
      change in pH or oxidative stress are of significant clinical interest as this
      approach offers the opportunity to link drug delivery to a specific location or
      disease state. This research news article reviews the current state of this field
      by examining a series of published articles that highlight the novelty and
      benefits of using responsive polymeric particles to achieve functionally-targeted
      drug delivery.

PMID- 22988561
TI  - Much still to be done to tackle irresponsible dog breeding.

PMID- 22988559
TI  - Mucus penetrating nanoparticles: biophysical tool and method of drug and gene
      delivery.
AB  - A method that could provide more uniform and longer-lasting drug and gene
      delivery to mucosal surfaces holds the potential to greatly improve the
      effectiveness of prophylactic and therapeutic approaches for numerous diseases
      and conditions, including sexually transmitted infections, cystic fibrosis,
      chronic rhinosinusitis, inflammatory bowel disease, and glaucoma to name a few.
      However, the body's natural defenses, including adhesive, rapidly cleared mucus
      linings coating nearly all entry points to the body not covered by skin, has
      limited the effectiveness of drug and gene delivery by nanoscale delivery
      systems. This article discusses the recent development of the "mucuspenetrating
      particle" or "MPP" nanotechnology, and how it has been used to both enhance
      understanding of the nanoscale barrier properties of human mucus secretions, and
      to achieve more uniform and longer-lasting drug delivery to mucosal tissues
      following topical administration. Drug loaded MPPs possess non-adhesive coatings
      that allow them to rapidly penetrate mucus layers through openings in the mucus
      mesh at rates nearly as fast as they would penetrate pure water. Critically, MPPs
      allow enhanced drug and gene delivery to mucosal tissues without diminishing the
      protective function of mucus. Recent progress in the development of MPPs as a
      biophysical tool to probe the length-scale dependent rheological properties of
      mucosal secretions and as a method for drug and gene delivery is highlighted.

PMID- 22988562
TI  - FMD reference lab receives funding to help deliver new control strategy.

PMID- 22988560
TI  - The changing face of brain tumours. Preface.

PMID- 22988563
TI  - Call to support badger vaccination programme, despite reservations.

PMID- 22988564
TI  - VMD to phase out importation of virginiamycin for veterinary use.

PMID- 22988565
TI  - EFSA suggests a toolbox of measures for assessing animal welfare.

PMID- 22988566
TI  - RCVS Council agrees new structure for specialisation.

PMID- 22988567
TI  - A systematic review on the application of cardiovascular risk prediction models
      in pharmacoeconomics, with a focus on primary prevention.
AB  - BACKGROUND: Long-term trials on the effectiveness of pharmacological treatment
      for primary cardiovascular disease prevention are scant. For that reason risk
      prediction models are used as a tool to project changes in cardiovascular disease
      incidence due to changes in risk factor levels observed in short-term randomized
      clinical trials. In this article, we summarize the literature on the application
      of these risk models in pharmacoeconomic studies for primary cardiovascular
      disease prevention interventions in high-income countries. METHODS AND RESULTS:
      We systematically reviewed the available literature on the application of
      cardiovascular disease risk models in pharmacoeconomic studies and assessed the
      quality of incorporation of risk models in these studies. Quality assessment
      indicated the distance between the characteristics of populations of the risk
      model and the studies reviewed, the frequent disagreement between risk model and
      study time horizons and the lack of proper consideration of the uncertainty
      surrounding risk predictions. CONCLUSION: Given that utilizing a risk model to
      project the effect of a pharmacological intervention to cardiovascular events
      provides an estimate of the intervention's clinical and economical impact,
      consideration should be paid to the agreement between the study and risk model
      populations as well as the level of uncertainty that these predictions add to the
      outcome of a decision-analytic model. In the absence of hard endpoint trials, the
      value of risk models to model pharmacological efficacy in primary cardiovascular
      disease prevention remains high, although their limitations should beacknowledged

PMID- 22988568
TI  - Big changes to skilled migration.

PMID- 22988569
TI  - [The Federation Council of Users and Residents of Quebec: another tool].

PMID- 22988570
TI  - [Spouse abuse. How does one react?].

PMID- 22988571
TI  - [A tax on carbonated and energy drinks?].

PMID- 22988572
TI  - [Oncotype DX. Treating breast cancer with or without chemotherapy. Deciding which
      is best].

PMID- 22988573
TI  - A primary nipple lymphoma diagnosed by a modified fine-needle aspiration method.
AB  - Primary breast lymphomas are uncommon. All reported primary breast lymphomas were
      in the breast parenchyma. Here we reported the first case of primary nipple
      lymphoma in a 76-year-old woman initially diagnosed using a modified fine-needle
      aspiration method. The aspirated material by this method had yielded adequate
      material for both cytomorphologic and flowcytometric analysis, as well as for
      molecular analysis of light chain rearrangement. In smears the atypical
      lymphocytes were predominantly middle-sized with irregular nuclei. Scattered
      large centroblast or immunoblast-like cells, a few reactive
      lymphocytes,histocytes, and few plasma cells were also observed. These findings
      suggested a low-grade lymphoma that was further confirmed by flow cytometry
      (CD19+/CD3-, positive for cytoplasmic kappa light chain but negative for lambda
      light chain) and molecular analysis (monoclonal rearrangement of immunoglobulin
      kappa chain). Immunohistochemical stains performed on the excised specimen showed
      that the tumor cells were positive forCD20 and CD79a but negative for
      cytokeratin, CD3, CD5,CD10, CD23, CD43, CD45RO, bcl-6, and cyclin-D1. The Ki-67
      proliferation index was less than 20%. Taking these together, the case was
      diagnosed as a primary MALT lymphoma of the nipple.FNA usually provides a better
      cell morphology than tissue sections, but pathologists have to face the sampling
      error and lack of immunophenotype information when subtyping lymphoma issues
      using FNA. With the help of flow cytometry and molecular analysis, more and more
      trials have proved the accuracy of FNA in diagnosis of lymphomas. Therefore, FNA
      could play an informative and diagnostic role in diagnosis of lymphoma

PMID- 22988574
TI  - Adaptive landscape genetics: pitfalls and benefits.
AB  - Landscape genetics offers a promising framework for assessing the interactions
      between the environment and adaptive genetic variation in natural populations. A
      recent workshop held at the University of Neuchatel brought together leading
      experts in this field to address current insights and future research directions
      in adaptive landscape genetics. Considerable amounts of genetic and / or
      environmental data can now be collected, but the forthcoming challenge is to do
      more with such manna. This requires a markedly better understanding of the
      genetic variation that is adaptive and prompts for advances in information
      management together with the development of a balance between theory and data.
      Moreover, showing the links between landscapes and adaptive genetic variation
      will ultimately move the field beyond association studies.

PMID- 22988575
TI  - Familial idiopathic basal ganglia calcification: unraveling the first genetic
      cause.

PMID- 22988577
TI  - Women set to benefit as US health reform rolls out.

PMID- 22988576
TI  - Generation of Dhx9-deficient clones in T-cell development with a mitotic
      recombination technique.
AB  - Mitotic recombination is an effective tool for generating mutant clones in
      somatic tissues. Because of difficulties associated with detecting and
      quantifying mutant clones in mice, this technique is limited to analysis of
      growth-related phenotypes induced by loss function of tumor suppressor genes.
      Here, we used the polymorphic CD45.1/CD45.2 alleles on chromosome 1 as pan
      hematopoietic markers to track mosaic clones generated through mitotic
      recombination in developing T cells. We show that lineage-specific mitotic
      recombination can be induced and reliably detected as CD45.1 or CD45.2 homozygous
      clones from the CD45.1/CD45.2 heterozygous background. We have applied this
      system in the analysis of a lethal mutation in the Dhx9 gene. Mosaic analysis
      revealed a stage-specific role for Dhx9 during T-cell maturation. Thus, the
      experimental system described in this study offers a practical means for mosaic
      analysis of germline mutations in the hematopoietic system.

PMID- 22988578
TI  - The Central African Republic's silent health crisis.

PMID- 22988579
TI  - India's patent laws under pressure.

PMID- 22988580
TI  - [Importance on the early diagnosis and treatment of autoimmune hepatitis].

PMID- 22988581
TI  - Not my turn.

PMID- 22988582
TI  - [Recent progress in laboratory diagnosis of autoimmune liver disease].

PMID- 22988583
TI  - [Differential diagnosis and therapy for autoimmune hepatitis and drug-induced
      liver injury].

PMID- 22988584
TI  - [Therapy for refractory primary biliary cirrhosis].

PMID- 22988585
TI  - [Role of specific T cells in autoimmune hepatitis].

PMID- 22988586
TI  - [The expression of NPRL2 protein in hepatocellular carcinoma and its clinical
      significance].

PMID- 22988587
TI  - [Dynamic alterations of angiotensin-converting enzyme, angiotensin-(1-7), and
      insulin-like growth factor binding protein-2 in fibrotic rat liver].

PMID- 22988588
TI  - [Changes of the serum adiponectin during treatment with peginterferon alpha-2a
      and ribavirin for chronic hepatitis C].

PMID- 22988589
TI  - [Diagnosis and management of autoimmune hepatitis with acute presentation].

PMID- 22988590
TI  - [Role of sex hormones in nonalcoholic fatty liver disease pathogenesis].

PMID- 22988591
TI  - Recommendations for physical activity  within the general population: is this all
      what we need to keep us healthy?

PMID- 22988592
TI  - Effect of outpatient exercise training  programmes in patients with chronic 
      heart failure: a systematic review.
AB  - BACKGROUND: Advantages of outpatient exercise training are reduced waiting lists,
      better compliance, reduced time investment by the patient with reduced travel
      expenses, and less dependence on other people to participate. Therefore, this
      systematic review studies the effects of outpatient exercise training programmes
      compared with usual care on exercise capacity, exercise performance, quality of
      life, and safety in patients with chronic heart failure. DESIGN: Systematic
      review with meta-analysis. METHODS: Randomized controlled trials concerning
      patients with chronic heart failure, with a left ventricular ejection fraction
      <=40%, were included. A meta-analysis was performed. RESULTS: Twenty-two studies
      were included. VO(2)max, 6-min walking test, and quality of life showed
      significant differences in favour of the intervention group of 1.85 ml/kg/min,
      47.9 m, and 6.9 points, respectively. In none of the studies, a significant
      relationship was found between exercise training and adverse events. CONCLUSION:
      This meta-analysis illustrates the efficacy and safety of outpatient training
      programmes for patients with chronic heart failure.

PMID- 22988593
TI  - Exercise training and cardiac  rehabilitation in patients with implantable 
      cardioverter defibrillators: a review of  current literature focusing on safety, 
      effects of exercise training, and the  psychological impact of programme 
      participation.
AB  - BACKGROUND: Indications for implantable cardioverter defibrillators (ICDs) have
      been widened considerably during the last decade due to the well-documented
      effect in the heart failure population. Exercise training (ET) has a 1A
      recommendation in heart failure. However, data on safety and efficacy of ET in
      patients with ICDs is sparse. ICD shocks are associated with reduced quality of
      life and increased mortality. Whether ET may have a beneficial effect in heart
      failure patients with an ICD is not well documented. METHODS: This review is
      based on a systematic search in the Pub Med database using the terms 'exercise
      training', 'implantable cardioverter defibrillator', and 'cardiac
      rehabilitation'. RESULTS: Nine studies were identified, comprising 1889 patients.
      The average duration of exercise-based cardiac rehabilitation (CR) was 9.6 weeks.
      Ten ICD therapies (seven shocks) were reported in the 834 patients with ICD
      during ET. Between exercise sessions and during follow up 182 events were
      recorded including 166 shocks. Three studies (2 randomized) showed that the
      control group representing sedentary patients were more prone to ICD discharge
      than patients undergoing CR/ET. In all studies the ICD patients improved their
      aerobic fitness following ET. Few studies report data on the effect of ET on
      anxiety and depression. CONCLUSION: Based on the current literature, ET in
      patients with an ICD seems to be safe and is not associated with increased risk
      of shocks. ET improves aerobic capacity in ICD patients, while effects on
      anxiety, depression and quality of life are still under debate.

PMID- 22988594
TI  - hERG K(+) channels: structure, function, and clinical significance.
AB  - The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of
      the rapid component of the delayed rectifier K(+) channel, Kv11.1, which are
      expressed in the heart, various brain regions, smooth muscle cells, endocrine
      cells, and a wide range of tumor cell lines. However, it is the role that Kv11.1
      channels play in the heart that has been best characterized, for two main
      reasons. First, it is the gene product involved in chromosome 7-associated long
      QT syndrome (LQTS), an inherited disorder associated with a markedly increased
      risk of ventricular arrhythmias and sudden cardiac death. Second, blockade of
      Kv11.1, by a wide range of prescription medications, causes drug-induced QT
      prolongation with an increase in risk of sudden cardiac arrest. In the first part
      of this review, the properties of Kv11.1 channels, including biogenesis,
      trafficking, gating, and pharmacology are discussed, while the second part
      focuses on the pathophysiology of Kv11.1 channels.

PMID- 22988595
TI  - [Four outstanding electrophysiologists].

PMID- 22988597
TI  - [How to overcome the crisis of American physiological society-advised from the
      former presidents].

PMID- 22988598
TI  - The injustice of infertility insurance coverage: an examination of marital status
      restrictions under state law.

PMID- 22988599
TI  - Donation after cardiac death: respecting patient autonomy and guaranteeing
      donation with guidance from Oregon's Death with Dignity Act.

PMID- 22988600
TI  - [Autophagy in pancreatic beta cells].

PMID- 22988601
TI  - [Molecular cellular mechanism of improved somatic sensation in vision deprived
      animals].

PMID- 22988602
TI  - [The first case of adenine phosphoribosyltransferase deficiency with APRT*Q0
      (M1I) mutation in Japan].
AB  - Adenine phosphoribosyltransferase (APRT) deficiency is an enzyme deficiency
      associated with purine metabolism, a hereditary disease that causes recurrent 2,
      8-DHA stone formation due to a complete or partial APRT defect and slowly damages
      the renal function. Since APRT deficiency can be treated to prevent its
      progression to renal insufficiency, it is important to detect APRT gene mutations
      and make a definite diagnosis early. A 3.5-year-old girl presented with painful
      urination and dysuria, and was admitted to our hospital. The analysis of stones
      collected after spontaneous passage revealed 2, 8-dihydroxyadenine (DHA)
      urolithiasis. To make a definite diagnosis, we searched for the APRT gene
      mutations reported in Japanese. However, no APRT Q0 mutation was identified. Only
      a heterogeneous mutation, APRT J, was noted. Subsequently, we screened the gene
      mutation regions reported from Europe and the United States and identified a
      heterogeneous mutation at the start codon of APRT Q0 from methionine to valine.
      This is the first report of this mutation in Japan. She was diagnosed with APRT
      deficiency caused by a compound heterogeneous mutation: APRT Q0/(M1V) APRT J
      (M136T). We believe that the same gene mutation has been inherited among other
      Japanese. For the future genetic diagnosis of APRT deficiency, this is a valuable
      case.

PMID- 22988603
TI  - Adsorption of textile reactive dyestuffs by treatment sludges of inorganic
      nature.
AB  - Colour removal from industrial effluents, particularly from the textile industry,
      has become an important requirement as the adverse effects ofdyestuffs, such as
      toxicity, on the environment have been proven. Adsorption is a commonly used
      treatment method for colour removal. Although activated carbon is very effective
      for this purpose, a number of natural materials and waste materials, such as
      waste sludges generated from treatment systems, have been tested to reduce the
      cost of the process. In this paper, sludges arising from the operation of an
      electrocoagulation process that used stainless steel or aluminium electrodes were
      investigated as adsorbents for decolorization of reactive dyestuffs.
      Electrocoagulation waste sludges produced with the use of stainless steel
      electrodes provided higher than 90% or complete decolorization of Crimson HEXL,
      Yellow HE4R and RB5 dyestuffs. The sludge produced with aluminium electrodes
      yielded colour adsorption between 95% and 100% at a 1 g/L dose and pH 8.5-9.1 for
      two of the dyestuffs; the removal of RB5 did not exceed 60% up to a 4.76 g/L
      dose. FeCl3 coagulation and adsorption using freshly precipitated coagulation
      sludge resulted in poor colour removals of 10% for all three dyestuffs. The
      superior colour adsorption performance of electrocoagulation waste sludges was
      attributed to modification of the surface properties of the sludges during the
      electrocoagulation operation. A batch-wise kinetic study indicated that the
      adsorption of RB5 on to electrocoagulation waste sludges was well fitted by the
      pseudo-second-order kinetic model, suggesting the intra-particle diffusion
      process as the rate-limiting step of the adsorption process.

PMID- 22988604
TI  - Biological treatment of nitrogen-rich refinery wastewater by partial nitritation
      (SHARON) process.
AB  - Wastewater discharges containing high nitrogen levels can be toxic to aquatic
      life and cause eutrophication. In this study, the application of the SHARON
      (Single reactor for High activity Ammonium Removal Over Nitrite) process for the
      treatment of refinery wastewater (sour water) was evaluated, in view of its
      coupling with the ANAMMOX (ANaerobic AMMonium OXidation) process. A Continuous
      Flow Stirred Tank Reactor was initially fed with a synthetic medium, and the
      applied NH4-N concentration and wastewater/synthetic medium ratio were
      progressively increased up to 2000 mgN/L and 100%, respectively. Despite the high
      potential toxic effect of the real wastewater, overall SHARON performance did not
      decrease with the increasing real wastewater/synthetic medium ratio, and biomass
      showed progressive acclimation to the toxic compounds in the real wastewater, as
      demonstrated by toxicity assessments. NH4-N and dissolved organic carbon removal
      efficiency were around 50% and 65%, respectively. Moreover, the effluent was
      characterized by a NO2-N/NH4-N ratio of 0.9 +/- 0.01 and low nitrate
      concentration (<30 mgN/L), in line with the requirements for the subsequent
      treatment by the ANAMMOX process.

PMID- 22988605
TI  - Removal of high concentration ammonia from wastewater by a combination of partial
      nitrification and anammox treatment.
AB  - Attached growth reactors were developed separately for solids retention time
      (SRT)-controlled partial nitrification and for anaerobic ammonia oxidation
      (Anammox) treatment, and a new nitrogen removal process is proposed for
      wastewater containing highly concentrated ammonia. For partial nitrification, an
      attached growth medium of polyurethane foam was used. Partial nitrification was
      achieved stably under a SRT of 4 days, and the abundance ratio of NO2(-)-N to the
      sum of NH4(+)-N, NO2(-)-N and NO3(-)-N was approximately 0.8 after 10 days. Under
      a SRT of4 days, the amoA gene concentrations of ammonia-oxidizing bacteria
      increased from 1 x 10(8) to 7 x 10(8) copies/l, whereas the 16S ribosomal RNA
      (16S rRNA) gene concentrations of nitrite-oxidizing bacteria did not increase.
      These results indicate that SRT-controlled operation is a promising technology
      for achieving partial nitrification. For the Anammox treatment, an attached
      growth medium of non-woven fabric was used. Inorganic nitrogen removal of
      approximately 80-90% was observed at an inorganic nitrogen loading rate of over
      10 kgN/(m3-medium.d) and an influent nitrogen concentration of 400 mgN/l. Our non
      woven fabric reactor showed similar or superior Anammox performance to that
      reported previously. By using a combination of these two rectors, we can develop
      a method that combines partial nitrification and Anammox treatment for effective
      and stable nitrogen removal.

PMID- 22988606
TI  - Effect of dual substrate environment on the formation of intracellular storage
      biopolymers.
AB  - We investigated the effect of a starch/acetate mixture on the formation of
      intracellular storage biopolymers compared with system behaviour where these
      compounds served as a single organic substrate. Three laboratory-scale sequencing
      batch reactors (SBRs) were operated at steady state with a sludge age of 8 days,
      one fed with acetate, another with starch and the third with a starch/acetate
      mixture. The SBR operation involved six cycles per day and continuous feeding
      during each cycle. Both acetate and starch generated storage biopolymers under
      continuous feeding. A poly-hydroxybutyrate (PHB) or glycogen pool was formed
      depending on the selected single substrate. In addition, around 18% of the
      acetate fed within each cycle was converted to PHB, while the remaining 82% was
      directly utilized for microbial growth. A higher glycogen formation of 44% was
      observed for starch. Substrate storage as PHB and glycogen continued with the
      feeding of the acetate/starch mixture. This observation, supported by
      microbiological analyses, indicated that the acclimated biomass in the
      corresponding SBR system sustained microbial fractions capable of performing
      metabolic functions associated with the formation of the two storage biopolymers.
      PHB accumulation was reduced as acetate could be more readily used for direct
      microbial growth in the presence of starch.

PMID- 22988607
TI  - Evaluation of pre-treatment processes for increasing biodegradability of agro
      food wastes.
AB  - Anaerobic digestion (AD) technology can be employed for treating sewage sludge,
      livestock waste or food waste. Generally, the hydrolysis stage is the rate
      limiting step of the AD processes for solid waste degradation. Therefore,
      physical, chemical and biological pre-treatment methods or their combination are
      required, in order to reduce the rate of such a limiting step. In this study,
      four methods (mechanical shredding, acid hydrolysis, alkaline hydrolysis and
      sonication) were tested to improve methane production and anaerobic
      biodegradability of different agro-food wastes and their mixtures. The kinetics
      of anaerobic degradation and methane production ofpre-treated individual wastes
      and selected mixtures were investigated with batch tests. Sonication at lower
      frequencies (37 kHz) proved to give the best results with methane productivity
      enhancements of over 100% in the case of pig manure and in the range of 10-47%
      for the other wastes assayed. Furthermore, the ultimate methane production was
      proportional, in all the cases, to the specific energy input applied (Es).
      Sonication can, thus, enhance waste digestion and the rate and quantity of biogas
      generated. The behaviour of the other pre-treatments under the conditions assayed
      is not significant. Only a slight enhancement of biogas production (around 10%)
      was detected for whey and waste activated sludge (WAS) after mechanical
      shredding. The lack of effectiveness of chemical pre-treatments (acid and
      alkaline hydrolysis) can be justified by the inhibition of the methanogenic
      process due to the presence of high concentrations of sodium (up to 8 g l(-1) in
      some tests). Only in the case of WAS did the acid hydrolysis considerably
      increase the biodegradability of the sample (79%), because in this case no
      inhibition by sodium took place. Some hints of a synergistic effect have been
      observed when co-digestion of the mixtures was performed.

PMID- 22988608
TI  - COD fractionation and denitrification potential of sonicated waste activated
      sludge liquids.
AB  - This study characterized sonicated waste activated sludge (WAS) liquids as a
      possible carbon source for nitrogen removal. In this context, the effect of
      sonication density on chemical oxygen demand (COD) and nitrogen release was
      determined by particle size distribution (PSD) analysis and anoxic batch
      experiments. The increase in ultrasonic density from 0.8 W/mL to 1.6 W/mL had a
      slight impact on the soluble COD/total COD ratio. The high ultrasonic energy
      input increased the solubilization of nitrogenous organic substances and resulted
      in a low COD/TKN (total Kjeldahl nitrogen) ratio, which is not appropriate for
      nutrient removal systems. The change in ultrasonic power had a significant effect
      on COD fractionation of sonicated WAS liquid. The COD fraction at the size ranges
      higher than 1600 nm decreased from 44% to 3% as the energy input increased. The
      increase in specific energy raised the COD fraction, at the size ranges of <2 nm,
      from 11% to 23%.The PSD-based COD fractionation showed that increasing the
      sonication density markedly changed the size distribution. The anoxic batch tests
      indicated that the specific denitrification rate of sonicated WAS liquid was in
      the range of that reported for the slowly biodegradable fraction of the domestic
      wastewater and higher than those reported for agro-food wastewater.

PMID- 22988609
TI  - Performance evaluation of a pilot-scale anaerobic membrane bioreactor (AnMBR)
      treating ethanol thin stillage.
AB  - The ethanol industry has grown rapidly during the past ten years, mainly due to
      increasing oil prices. However, efficient and cost-effective solutions for
      treating thin stillage wastewater have still to be developed. The anaerobic
      membrane bioreactor (AnMBR) technology combines classical anaerobic treatment in
      a completely-stirred tank reactor (CSTR) with membrane separation. The
      combination of these two technologies can achieve a superior effluent quality and
      also increase biogas production compared to conventional anaerobic solutions. A
      pilot-scale AnMBR treating thin stillage achieved very high treatment
      efficiencies in terms of chemical oxygen demand (COD) and total suspended solids
      (TSS) removal (>98%). An average permeate flux of 4.3 L/m2 x h was achieved at
      relatively low transmembrane pressure (TMP) values (0.1-0.2 bars) with flat-sheet
      membranes. Experience gained during the pilot-scale studies provides valuable
      information for scaling up of AnMBRs treating complex and high-strength
      wastewaters.

PMID- 22988610
TI  - Fate and effect of xenobiotics on biodegradation processes: basis for
      respirometric appraisal.
AB  - The paper mainly focused on illustrating the merit of respirometric analysis in
      assessing the inhibitory/toxic impact of xenobiotics on substrate biodegradation.
      It also evaluated biodegradation characteristics of these chemicals at continuous
      exposure through acclimation ofthe microbial culture. The nature and role
      ofoxygen uptake rate (OUR) profiles were discussed in conjunction with
      appropriate modelling, which should incorporate dissolved oxygen as an
      indispensable component for respirometric evaluation. Emphasis was placed upon
      differentiating acute effects from chronic impact, which may be totally different
      as it involves biodegradation of the chemical due biomass acclimation. Three case
      studies, each involving OUR measurements and process modelling, were presented
      for this purpose. The first one related to the inhibitory action of
      pharmaceutical effluent when mixed with plain-settled tannery wastewater. The
      second investigated the fate of H-acid, a commercially important naphthalene
      sulfonate, which exerted no adverse effect on substrate biodegradation, while
      remaining intact before and after a long acclimation period. The third one
      involved 2,6-dihydroxybenzoic acid, a naturally occurring organic compound in
      olive oil wastewater, which became biodegradable after acclimation by the
      development ofa specific microbial biomass fraction, while it heavily inhibited
      substrate biodegradation at first exposure. Model evaluation of the experimental
      data could provide related information on process stoichiometry and kinetics in
      all studies.

PMID- 22988611
TI  - Comparison of simultaneous and separate processes: saccharification and
      thermophilic L-lactate fermentation of catch crop and aquatic plant biomass.
AB  - Catch crop candidates (corn, guinea grass) for recovering nutrients from farm
      soil and aquatic plants (water caltrop, water hyacinth) were utilized to produce
      L-lactic acid. The efficiencies ofpre-treatment methods for enzymatic
      saccharification and L-lactate production of two fermentation processes,
      thermophilic simultaneous saccharification and fermentation (SSF), as well as
      separate saccharification and fermentation, were compared. Conditions were set at
      55 degrees C and pH 5.5 for non-sterile fermentation. Alkaline/peroxide pre
      treatment proved the most effective for saccharification in pre-treated corn,
      guinea grass, water caltrop and water hyacinth with glucose yields of 0.23, 0.20,
      0.11 and 0.14 g/g-dry native biomass (24-hour incubation period), respectively.
      Examination of the two types of thermophilic L-lactate fermentation employed
      following alkaline/peroxide pre-treatment and saccharification demonstrated that
      the L-lactate yield obtained using SSF (0.15 g/g in the case of corn) was lower
      than that obtained using separate saccharification and fermentation (0.28 g/g in
      the case of corn). The lower yield obtained from SSF is likely to have resulted
      from the saccharification conditions used in the present study, as the
      possibility of cellulase deactivation during SSF by thermophilic L-lactate
      producing bacteria existed. A cellulase that retains high activity levels under
      non-sterile conditions and a L-lactate producer without cellulose hydrolysis
      activity would be required in order for SSF to serve as an effective method of L
      lactate production.

PMID- 22988612
TI  - H2O2/UV-C treatment of textile preparation wastewater: kinetic investigation on
      alternative combinations of commercial textile preparation auxiliaries.
AB  - Four different textile preparation effluents were simulated to examine the
      applicability of the hydrogen peroxide/ultraviolet-C (H2O2/UV-C) advanced
      oxidation process for the treatment of real textile preparation (desizing,
      scouring and bleaching) wastewater bearing the non-ionic surfactant nonyl phenol
      decaethoxylate (NP-10). In the absence of any textile preparation chemical, NP-10
      degradation was complete in 15 min (rate coefficient: 0.22 min(-1)) accompanied
      by 78% chemical oxygen demand (COD) (rate coefficient: 0.026 min(-1)) and 57%
      total organic carbon (TOC) (rate coefficient: 0.014 min(-1)) removals achieved
      after 60 min photochemical treatment. H2O2 consumption rates were not
      significantly affected by the introduction of carbonate and chloride ions
      (average rate coefficient: 0.032 min(-1)) at pH values <11.5, above which H2O2
      dissociation to its conjugate base HO2(-) became pronounced. The organic,
      phosphonate-based sequestering agents competed with NP-10 for UV-C light
      absorption and HO* radicals. H2O2/UV-C oxidation of the simulated textile
      preparation effluent containing 3.0 g L(-1) Cl(-), 1.5 g L(-1) NaOH and 1.0 g L(
      1) diethylenetriamine pentamethylene phosphonic acid (DTPMP) resulted in the
      worst treatment performance due to its high pH and organic carbon content. For
      this textile preparation effluent, NP-10 abatement was complete in 100min (rate
      coefficient: 0.018 min(-1)), while COD and TOC removals dropped down to only 16%
      and 8%, respectively, achieved after 60 min treatment. The highest H2O2/UV-C
      oxidation efficiency resulting in 34% COD and 28% TOC removals was obtained for
      the simulated textile preparation effluent comprising of 3.0 g L(-1) Cl(-), 1.5 g
      L(-1) NaOH and 1.0 g L(-1) 1-hydroxy ethylidene-1,1-diphosphonic acid (HEDP). For
      this textile preparation effluent, NP-10 degradation was complete after 50 min
      (rate coefficient: 0.061 min(-1)) exposure to H2O2/UV-C treatment.

PMID- 22988613
TI  - Emission of greenhouse gases from controlled incineration of cattle manure.
AB  - Greenhouse gas emission is a potential limiting factor in livestock farming
      development. While incineration is one approach to minimize livestock manure,
      there are concerns about significant levels of nitrogen and organic compounds in
      manure as potential sources of greenhouse gas emissions (N2O and CH4). In this
      study, the effects of various incineration conditions, such as the furnace
      temperature and air ratio on N2O and CH4 formation behaviour, of cattle manure
      (as a representative livestock manure) were investigated in a pilot rotary kiln
      furnace. The results revealed that N2O emissions decreased with increasing
      temperature and decreasing air ratio. In addition, CH4 emissions tended to be
      high above 800 degrees C at a low air ratio. The emission factors for N2O and CH4
      under the general conditions (combustion temperature of 800-850 degrees C and air
      ratio of 1.4) were determined to be 1.9-6.0% g-N2O-N/g-N and 0.0046-0.26% g-CH4/g
      burning object, respectively. The emission factor for CH4 differed slightly from
      the published values between 0.16 and 0.38% g-CH4/g-burning object. However, the
      emission factor for N2O was much higher than the currently accepted value of 0.7%
      g-N2O-N/g-N and, therefore, it is necessary to revise the N2O emission factor for
      the incineration of livestock manure.

PMID- 22988614
TI  - Decolourization of the azo dye Orange G in aqueous solution via a heterogeneous
      Fenton-like reaction catalysed by goethite.
AB  - Decolourization of the azo dye Orange G (OG) was investigated by using
      goethite/H2O2 as a heterogeneous Fenton-like reagent. Five principle operational
      parameters, namely pH, ion strength, concentrations ofgoethite (alpha-FeOOH) and
      hydrogen peroxide (H2O2), and reaction temperature, were taken into account to
      investigate how these controlling factors mediated OG decolourization. Goethite
      surfaces catalysed a Fenton-like reaction responsible for decolourizing OG
      following pseudo-first-order kinetics (R2 > 0.964). This process was effective
      but seriously impacted by the medium pH and the dosages of both alpha-FeOOH and
      H2O2. The decolourization efficiencies of OG increased with the decrease of
      solution pH and NaCl (chloride ion) concentration and/or the increase of H2O2.
      The acidic aqueous medium conditions were likely favourable due to the surface
      adsorption of the negatively charged OG leading to the promotion of decolourizing
      OG. The apparent activation energy (E) for this reaction was 42.18 kJ mol(-1), a
      relatively low value. This is consistent with the OG decolourization being
      enhanced with the reaction temperature increase.

PMID- 22988615
TI  - Application of activated carbon impregnated with metal oxides to the treatment of
      multi-contaminants.
AB  - In this study, as a novel technique for the simultaneous treatment of As(III) and
      phenol in a single column reactor, different ratios of manganese-impregnated
      activated carbon (Mn-AC) and iron-impregnated activated carbon (Fe-AC) were
      applied in a bench-scale column reactor. In this bench-scale test, the column
      system packed with both Mn-AC and Fe-AC (binary system) was identified as the
      best system due to the good oxidation efficiency of As(III) to As(V) by Mn-AC,
      which reasonably controlled the mobility of total arsenic through adsorption of
      As(V), along with efficient removal of phenol . When the pilot-scale column
      reactor, packed with equal amounts of Mn-AC and Fe-AC, was applied for the
      removal of As(III) and phenol, the oxidation of As(III) by 1 g of Mn-AC for up to
      110 days and the removal of phenol by total 1 g of Mn-AC and Fe-AC for up to 100
      days were 1.81 x 10(-4) g and 8.20 x 10(-4) g, respectively. Based on this work,
      Fe-AC and Mn-AC can be regarded as a promising filter material in the treatment
      of wastewater contaminated with organic compounds, such as phenol, and redox
      sensitive ions, such as As(III).

PMID- 22988616
TI  - Vapour-liquid equilibrium relationship between toluene and mixed surfactants.
AB  - Micellar partitioning of volatile organic compounds (VOCs) in surfactant
      solutions and its effects on vapour-liquid equilibrium is fundamental to the
      overall design and implementation ofsurfactant-enhanced remediation. Knowledge of
      the vapour-liquid equilibrium partitioning coefficients for VOCs, especially in
      contaminated soils and groundwater in which they exist, is required. Headspace
      experiments were performed to quantify the effect of three mixed surfactants,
      cetyltrimethyl ammonium bromide (CTMAB) with tetrabutylammonium bromide (TBAB),
      sodium dodecyl sulphate (SDS) with Triton X-405 (TX405), and CTMAB with Triton X
      100 (TX100), on the apparent Henry's constants (Hc) of toluene at temperatures
      ranging from 25 degrees C to 40 degrees C. The Hc values were significantly
      reduced in the presence of all three mixed surfactants at concentrations above
      their critical micelle concentrations (CMC). Mixed micellar partitioning, showing
      effects on the vapour-liquid equilibrium of toluene, was primarily responsible
      for the significant reduction of Hc in their mixed systems. The mixed surfactants
      CTMAB-TX100 had the greatest effect on Hc above the CMC, followed by SDS-TX405,
      then CTMAB-TBAB. Mixed systems of CTMAB-TX100 decreased Hc at concentrations
      significantly lower than the SDS-TX405 and CTMAB-TBAB concentrations, because of
      to the lower CMC of CTMAB-TX100. Vapour-liquid equilibrium data were also tested
      against the model (Hc = H/(1 + K(X - CMC)) that described the partitioning of
      VOCs in vapour-water-micelle phases. The correlation of Hc with mixed surfactant
      concentrations (X) and CMC can be utilized as an effective tool to predict the Hc
      by mixed surfactants.

PMID- 22988617
TI  - Recycling of hazardous waste as a new resource for nickel extraction.
AB  - Nickel extraction from hazardous waste by sulphuric acid leaching has been
      investigated. This study was performed to assess the effects of different
      parameters such as reaction time, acid concentrations, solid-liquid ratio,
      particle size, stirring speed and reaction temperature on nickel extraction from
      zinc plant residue, with the aim of recycling this waste and reducing its
      environmental impact. It was shown that the nickel extraction increased with
      increasing reaction time, acid concentration and temperature, and decreasing
      solid:liquid ratio and particle size. Leaching residues were subjected to
      chemical analysis, XRD and SEM studies, and the results indicated that it is
      possible to extract more than 96% nickel content by optimization of leaching
      conditions. These results provided important data on the recovery of nickel from
      toxic hazardous waste, and leaching is a suitable method for this waste
      management. The results also showed that this waste can be used as a secondary
      resource for nickel extraction.

PMID- 22988618
TI  - Leaching of nitrogen and base cations from calcareous soil amended with organic
      residues.
AB  - The potential for groundwater and surface water pollution by nutrients in organic
      residues, primarily nitrogen (N) and base cations (K+, Na+, Ca2+, Mg2+), is a
      consideration when applying such residues to land. In this study, we used a
      laboratory column leaching procedure to examine the leaching of N, K+, Na+, Ca2+
      and Mg2+ in soils treated with two types of raw organic residues (poultry manure
      and potato residues) and one municipal waste compost, which are currently
      recycled on agricultural land in Iran. Each organic residue was thoroughly mixed
      with two different soils (sandy loam and clay) at the rate of 3%. Soil columns
      were leached at 4-d intervals for 92 d with distilled water, and effluents were
      analysed for pH, EC, nitrate (NO3(-)-N), ammonium (NH4(+)-N) K+, Na+, Ca2+ and
      Mg2+. The results indicated that the amounts of NO3(-)-N and NH4(+)-N leached
      from the poultry manure and potato residues could represent very important
      economic losses of N and pose an environmental threat under field conditions. The
      sandy loam soil amended with poultry manure lost the highest amount of NO3(-)-N
      (206.4 kg ha(-1)), and clay soil amended with poultry manure lost the highest
      amounts of NH4(+)-N (454.3 kg ha(-1)). The results showed that a treatment
      incorporating 3% of municipal waste compost could be used without negative
      effects to groundwater N concentration in clay soil. Significant amounts of K+,
      Na+, Ca2+, and Mg2+ were leached owing to the application of poultry manure,
      potato and municipal waste compost to soils. There was a positive relationship
      between K+, Na+, Ca2+, and Mg2+ with NO3(-)-N and NH4(+)-N leached in soils.
      Analysis of variance detected significant effects of amendment, soil type and
      time on the leaching NO3(-)-N, NH4(+)-N, K+, Na+, Ca2+ and Mg2+.

PMID- 22988619
TI  - UV-H2O2 degradation of methyl orange catalysed by H3PW12O40/activated clay.
AB  - A catalyst consisting of phosphotungstic acid (H3PW12O40) combined with activated
      clay was prepared by the impregnation method, and an experiment was carried out
      to evaluate the catalytic activity of the H3PW12O40/activated clay for the
      degradation of methyl orange (MO) in the UV-H2O2 process. The degradation ratio
      of MO can be affected by H2O2 concentration, reaction time, catalyst dosage, pH
      and temperature. The reaction temperature should be controlled at less than 70
      degrees C, and the catalyst has a wide applicable pH range in the UV-H2O2
      process. Hydroxyl radicals were generated in the UV-H2O2 system under the action
      of H3PW12O40/activated clay, and MO was degraded by hydroxyl radicals. Compared
      with traditional catalysts used in UV-H2O2 systems, H3PW12O40/activated clay has
      certain advantages for its practical application.

PMID- 22988620
TI  - Cosmetics as a potential source of environmental contamination in the UK.
AB  - Chemicals of emerging concern (CECs) are frequently used in cosmetic formulations
      and can potentially reach the environment at concentrations that may cause harm.
      A methodology was developed to assess over 120 chemicals assembled from product
      ingredient listings to identify and validate potential CECs in cosmetics, based
      on Annex XIII of REACH legislation. Ten potential CECs were identified:
      polydimethylsiloxane, butylated hydroxylanisole (BHA), butylated hydroxytoluene,
      triclosan, nano titanium dioxide, nano zinc oxide, butylparaben, diethyl
      phthalate, octinoxate methoxycinnamate and benzophenone. These chemicals were
      quantified based on their consumption and concentrations in cosmetics and
      percentage market penetration. The initial predicted environmental concentrations
      (PEC initial) were estimated to determine their exposure to the environment. With
      the exception of BHA, the PEC initial highlighted levels of exposure to the
      environment that triggered the need for further investigation of the chemicals.
      These chemicals were linked to cosmetics to highlight products with the potential
      to cause environmental harm. Skin care products had the highest quantities of
      CECs, with titanium dioxide and zinc oxide nanomaterials being dominant potential
      contaminants. Further research is required to assess the exposure pathways and
      fate of these chemicals to determine environmental risks associated with their
      use and disposal.

PMID- 22988621
TI  - Phytoremediation of heavy metals from aqueous solutions by two aquatic
      macrophytes, Ceratophyllum demersum and Lemna gibba L.
AB  - Wetland plants are being used successfully for the phytoremediation of trace
      elements in natural and constructed wetlands. Under the present investigation,
      two aquatic macrophytes, Ceratophyllum demersum and Lemna gibba, were tested for
      their effectiveness at removing two toxic metals (Pb and Cr). These plants were
      grown at four different concentrations in single-metal solutions of the two
      metals and were separately harvested after 2, 4, 6, 9 and 12 days in a laboratory
      experiment. These plants performed extremely well at removing the chromium and
      lead from their solutions and were capable of removing up to 95% of lead and 84%
      of chromium during the 12-day incubation period. The removal continued through
      the 12 days and up to the highest value on the 12th day of the experiment. The
      results revealed that, of the two species, L. gibba was the most efficient for
      the removal of selected heavy metals. The plants accumulated heavy metals without
      the production of any toxicity or reduction in growth.

PMID- 22988622
TI  - Stormwater run-off from an industrial log yard: characterization, contaminant
      correlation and first-flush phenomenon.
AB  - The stormwater run-off generated in an industrial log yard during eight run-off
      events was studied with the main focus on the transport of toxic metals.
      Associations between water quality constituents and potential surrogates were
      evaluated by correlation analysis. The first-flush phenomenon was verified by
      normalized M(V) curves. The results have shown that, whereas some metals such as
      Zn, Ba, Cd, As and Fe were always detected in these waters, others (Cr, Pb, Cu,
      Ni, V, Co) were not. Large variations in the water constituents' concentrations
      were observed, with Fe, Pb and V being the most variable ones. Concentrations of
      Zn and Cu in the run-off waters exceeded the values established by the Swedish
      environmental authorities in 100% and 97% of samples, respectively. The
      correlation analyses indicated TSS as a potential surrogate of Pb, V, Co, Ni, As,
      Ba, Cr and COD (0.949 > R > 0.808), making it reasonable to state that a
      treatment system with focus on TSS removal would also reduce toxic metals from
      these waters. The first-flush phenomenon was evident for most of the
      constituents. Significant differences (p < 0.05) in the first-flush magnitude of
      different run-off events were observed confirming that hydro-meteorological
      variables such as dry period, precipitation duration and average intensity play
      important roles. Metal loads originating from the log yard were mainly composed
      ofZn, Cu and Ba. Knowledge of the physicochemical characteristics, discharge
      dynamics and the storm variables involved in the process is a crucial step for
      the proposal and implementation of a stormwater management programme.

PMID- 22988623
TI  - Linking bacterial diversity and geochemistry of uranium-contaminated groundwater.
AB  - To understand the link between bacterial diversity and geochemistry in uranium
      contaminated groundwater, microbial communities were assessed based on clone
      libraries of 16S rDNA genes from the USDOE Oak Ridge Field Research Centre (FRC)
      site. Four groundwater wells (GW835, GW836, FW113-47 and FW215-49) with a wide
      range of pH (3 to 7), nitrate (44 to 23,400 mg L(-1)), uranium (0.73 to 60.36 mg
      L(-1)) and other metal contamination, were investigated. Results indicated that
      bacterial diversity correlated with the geochemistry of the groundwater.
      Microbial diversity decreased in relation to the contamination levels of the
      wells. The highly contaminated well (FW113-47) had lower gene diversity than less
      contaminated wells (FW215-49, GW835 and GW836). The high concentrations of
      contaminants present in well FW113-47 stimulated the growth of organisms capable
      of reducing uranium (Shewanella and Pseudomonas), nitrate (Pseudomonas,
      Rhodanobacter and Xanthomonas) and iron (Stenotrophomonas), and which were unique
      to this well. The clone libraries consisted primarily of sequences closely
      related to the phylum Proteobacteria, with FW-113-47 almost exclusively
      containing this phylum. Metal-reducing bacteria were present in all four wells,
      which may suggest that there is potential for successful bioremediation of the
      groundwater at the Oak Ridge FRC. The microbial community information gained from
      this study and previous studies at the site can be used to develop predictive
      multivariate and geographical information system (GIS) based models for microbial
      populations at the Oak Ridge FRC. This will allow for a better understanding of
      what organisms are likely to occur where and when, based on geochemistry, and how
      these organisms relate to bioremediation processes at the site.

PMID- 22988624
TI  - Composting sewage sludge amended with different sawdust proportions and textures
      and organic waste of food industry--assessment of quality.
AB  - The quality of compost made from dewatered sewage sludge, sawdust (SD) and
      organic wastes of a potato-processing industry (OW), in terms of chemical and
      biological properties, was assessed. Mixtures of the sludge, SD and OW were
      composted for 57 days in insulated containers at two C:N ratios (approximately 30
      : 1 and approximately 20 : 1) and SD textures (coarse- and fine-textured SD). The
      parameters monitored over this period were pH, electrical conductivity (EC), C:N
      ratio, CO2 evolution and two spectrophotometric ratios (Q2/6 and Q2/4). All the
      studied parameters were in general similarly influenced by initial C:N ratio and
      texture of SD except for EC, Q2/6 and Q2/4. At high C:N ratio of both textures,
      the EC of the final products increased but were less than those of low C:N ratio
      of both textures. Thus, final product can be used alone as growth medium without
      the need for grinding or blending with other materials. The spectrophotometric
      ratios (Q2/6 and Q2/4) dramatically decreased two weeks after composting and then
      slightly increased at the end of composting process. However, coarse-textured SD
      at the low C:N ratio and fine-textured SD at both C:N ratios resulted in lower
      Q2/6 and Q2/4 ratios, reflecting a better degree of aromatic condensation and
      organic matter humification. Considering these parameters, co-composting sludge
      with fine-textured SD and OW at high initial C:N ratio would represent the best
      compromise.

PMID- 22988625
TI  - Disinfection of water using Pt- and Ag-doped TiO2 photocatalysts.
AB  - In this article we have reported heterogeneous photocatalytic disinfection using
      pristine and Ag- and Pt-doped nano TiO2 under near-UV light and solar light
      irradiation. Disinfection experiments were conducted in slurry reactors with
      Escherichia coli, artificial light and sunlight. The influence of various amounts
      of Pt and Ag loading (0.5% to 5%) on the E. coli inactivation was examined and
      results indicated that 5% Pt-TiO2 and 0.5% Ag-TiO2 showed the highest
      photocatalytic E. coli inactivation. The Pt- and Ag-doped photocatalysts were
      characterized using XPS and TEM analysis. The influence of experimental
      parameters such as various photocatalysts, photocatalyst concentration, reactor
      geometry effect, pH and temperature on the photocatalytic disinfection was
      studied. The experimental results show that sunlight or near-UV light with TiO2
      photocatalyst strongly inactivates E. coli. The Ag-TiO2 photocatalyst was the
      most efficient photocatalyst tested for bactericidal activity. A plausible
      mechanism ofphotocatalysed E. coli inactivation is discussed. In conclusion, the
      doped nano TiO2 photocatalysts is a potential candidate for E. coli inactivation.

PMID- 22988626
TI  - Biosorption of cadmium by a metal-resistant filamentous fungus isolated from
      chicken manure compost.
AB  - A fungus, XJ-1, isolated from chicken manure compost was phylogenetically related
      to Penicillium chrysogenum. The minimum inhibitory concentrations of the fungus
      for Cd2+, Cu2+, Cr3+, Cr6+, Co2+ and Zn2+ were 300, 85, 55, 8, 25 and 70mM on
      plates and 200, 65, 30, 2, 30 and 48mM in liquid media, respectively. Biosorption
      of Cd2+ by XJ-1 was investigated as a function of initial pH, contact time,
      biomass loading and Cd+ concentration. According to the Langmuir isotherm, the
      maximum adsorption of Cd2+ was 100.41 mg g(-1) dry biomass. Analyses using FTIR,
      SEM and XPS showed that the functional groups -OH and -C=O on the XJ-1 cell wall
      are the dominant binding sites for Cd2+. The results indicate that XJ-1 biomass
      is an efficient biosorbent for Cd2+ and has great potential for the in situ
      remediation of environments contaminated with heavy metals.

PMID- 22988627
TI  - Efficiency of biological activator formulated material (BAFM) for volatile
      organic compounds removal--preliminary batch culture tests with activated sludge.
AB  - During biological degradation, such as biofiltration of air loaded with volatile
      organic compounds, the pollutant is passed through a bed packed with a solid
      medium acting as a biofilm support. To improve microorganism nutritional
      equilibrium and hence to enhance the purification capacities, a Biological
      Activator Formulated Material (BAFM) was developed, which is a mixture of solid
      nutrients dissolving slowly in a liquid phase. This solid was previously
      validated on mineral pollutants: ammonia and hydrogen sulphide. To evaluate the
      efficiency of such a material for biodegradation of some organic compounds, a
      simple experiment using an activated sludge batch reactor was carried out. The
      pollutants (sodium benzoate, phenol, p-nitrophenol and 2-4-dichlorophenol) were
      in the concentration range 100 to 1200 mg L(-1). The positive impact of the
      formulated material was shown. The improvement of the degradation rates was in
      the range 10-30%. This was the consequence of the low dissolution of the
      nutrients incorporated during material formulation, followed by their consumption
      by the biomass, as shown for urea used as a nitrogen source. Owing to its twofold
      interest (mechanical resistance and nutritional supplementation), the Biological
      Activator Formulated Material seems to be a promising material. Its addition to
      organic or inorganic supports should be investigated to confirm its relevance for
      implementation in biofilters.

PMID- 22988628
TI  - Chemical phosphorus removal: a clean strategy for piggery wastewater management
      in Brazil.
AB  - The intensive production of animal protein is known to be an environmental
      polluting activity, especially if the wastewater produced is not managed
      properly. Swine production in Brazil is growing, and technologies to manage all
      pollutants present in the wastewater effluent are needed. This work presents a
      case of study of phosphorus (P) removal from piggery wastewater using Ca(OH)2,
      and demonstrates the feasibility of this strategy for P management. The effluent
      of a swine manure treatment plant was treated with Ca(OH)2. According to the
      addition of Ca(OH)2 the pH of the effluent ranged from 8.0 to 10.0. Different
      conditions of sludge dewatering were evaluated, and the chemical composition of
      sludge was investigated. Ion chromatography analysis of effluent samples showed
      that 92% of total P (TP) was present as soluble P (SP) whereas 75% of SP species
      were present as phosphate. The efficiency of P removal was typically 90% at pH
      8.5 and higher than 98% at pH 10.5. The sludge was separated by sedimentation,
      centrifugation or filtration and dried. The TP content of dried sludge was 9.3%
      (w/w). X-ray diffraction analysis of the dry sludge showed the presence of
      amorphous compounds of Ca and P, which is an indication that the sludge obtained
      from the swine manure treatment has a potential for application as biofertilizer.

PMID- 22988629
TI  - Development of water movement model as a module of moisture content simulation in
      static pile composting.
AB  - This paper presents a mathematical model of vertical water movement and a
      performance evaluation of the model in static pile composting operated with
      neither air supply nor turning. The vertical moisture content (MC) model was
      developed with consideration of evaporation (internal and external evaporation),
      diffusion (liquid and vapour diffusion) and percolation, whereas additional water
      from substrate decomposition and irrigation was not taken into account. The
      evaporation term in the model was established on the basis of reference
      evaporation of the materials at known temperature, MC and relative humidity of
      the air. Diffusion of water vapour was estimated as functions of relative
      humidity and temperature, whereas diffusion of liquid water was empirically
      obtained from experiment by adopting Fick's law. Percolation was estimated by
      following Darcy's law. The model was applied to a column of composting wood chips
      with an initial MC of 60%. The simulation program was run for four weeks with
      calculation span of 1 s. The simulated results were in reasonably good agreement
      with the experimental results. Only a top layer (less than 20 cm) had a
      considerable MC reduction; the deeper layers were comparable to the initial MC,
      and the bottom layer was higher than the initial MC. This model is a useful tool
      to estimate the MC profile throughout the composting period, and could be
      incorporated into biodegradation kinetic simulation of composting.

PMID- 22988630
TI  - Efficiency influence of exogenous betaine on anaerobic sequencing batch biofilm
      reactor treating high salinity mustard tuber wastewater.
AB  - When treating a composite mustard tuber wastewater with high concentrations of
      salt (about 20 g Cl(-) L(-1)) and organics (about 8000 mg L(-1) COD) by an
      anaerobic sequencing batch biofilm reactor (ASBBR) in winter, both high salinity
      and low temperature will inhibit the activity of anaerobic microorganisms and
      lead to low treatment efficiency. To solve this problem, betaine was added to the
      influent to improve the activity of the anaerobic sludge, and an experimental
      study was carried to investigate the influence of betaine on treating high
      salinity mustard tuber wastewater by the ASBBR. The results show that, when using
      anaerobic acclimated sludge in the ASBBR, and controlling biofilm density at 50%
      and water temperature at 8-12 degrees C, the treatment efficiency of the reactor
      could be improved by adding the betaine at different concentrations. The
      efficiency reached the highest when the optimal dosage ofbetaine was 0.5 mmol L(
      1). The average effluent COD, after stable acclimation, was 4461 mg L(-1).
      Relative to ASBBR without adding betaine, the activity of the sludge increased
      significantly. Meanwhile, the dehydrogenase activity of anaerobic microorganisms
      and the COD removal efficiency were increased by 18.6% and 18.1%, respectively.

PMID- 22988631
TI  - Preparation of paper mill sludge-based granular activated carbon fillers for
      fluidized-bed bioreactor (FBBR).
AB  - Paper mill sludge (PMS) was utilized to prepare granular activated carbon (GAC)
      fillers for fluidized-bed bioreactor (FBBR) through stream activation. The
      properties of the PMS were tested and the optimum conditions for the production
      process were determined. Then, the GAC fillers were used in the FBBR to
      investigate the capacity for wastewater treatment. The results showed that the
      optimal conditions were: carbonization temperature of 450 degrees C,
      carbonization time of 50 min, activation temperature of 800 degrees C and
      activation time of 60 min. The specific surface area of the GAC fillers was 130
      m2/g and the grain density was 1.34 x 10(3) kg/m3. The wastewater treatment
      results showed that after40 days ofrunning, under the conditions of influent COD
      of 800 mg/L and HRT of2 h, the COD removal efficiency was about 90%, which
      demonstrated that PMS-based GAC fillers were feasible for FBBR.

PMID- 22988632
TI  - Highly efficient removal of Cu(II), Zn(II), Ni(II) and Fe(II) from electroplating
      wastewater using sulphide from sulphidogenic bioreactor effluent.
AB  - A bench-scale, stirred-tank batch precipitator was used to assess the selective
      removal of Cu2+, Zn2+, Ni2+ and Fe2+ from acidic electroplating wastewater using
      sulphide from a sulphidogenic bioreactor effluent. At pH approximately 1.7, >99%
      of Cu was selectively precipitated, over Zn, Ni and Fe, from the wastewater as
      pure CuS by recycling H2S from the bioreactor effluent via N2 sparging, resulting
      in a Cu effluent concentration <0.4 mg/L. The rate of Cu precipitation increased
      from 1.6 to 6.4 mg Cu/(L x min) when the pH of the bioreactor effluent decreased
      from 7.5 to 5.5. Experiments focusing on the precipitation of Zn, Ni and Fe from
      the wastewater devoid of Cu (at pH approximately 1.7), using sulphide-rich
      bioreactor effluent, achieved approximately 85-97% precipitation efficiency for
      Zn, approximately 25-92% for Ni, and approximately 2-99% for Fe, depending on the
      initial sulphide/metal molar ratio. The sulphide/metal ratio of 1.76 was found to
      be optimal for the precipitation of Zn, Ni and Fe with sulphides and, to a lesser
      extent, with hydroxides, resulting in residual metal concentrations of 1 mg Zn/L,
      3 mg Ni/L, and 0.5 mg Fe/L. These findings suggest the potential of waste
      biogenic sulphides for the selective recovery of valuable metals from acidic
      metal-rich industrial wastewaters.

PMID- 22988633
TI  - Nano-structured Mg-doped Fe2O3-ferrihydrite powder--a new adsorbent for cation
      removal from aqueous solutions.
AB  - The present studies were undertaken with a view to developing a low-cost,
      efficient adsorbent for removal of heavy metal ions from aqueous solutions. A new
      cost-effective nano-structured Mg-doped Fe2O3-ferrihydrite adsorbent exhibiting
      high uptake capacities for various cations was synthesized. After preliminary
      testing of a series of Mg-doped (0.38 to 0.98%) samples for Pb(II), Cd(II),
      Cu(II) or Co(II) adsorption, a typical sample containing 55.7% Fe and 0.38% Mg
      was chosen for detailed characterization studies (XRD, TG-DTA, FTIR and TEM
      techniques). The adsorption behaviour of cations on the prepared nano powder was
      studied under various experimental conditions. The generated data were fitted to
      kinetic and isotherm models. The Langmuir monolayer capacities were 99.1, 83.3,
      111.1 and 151.5 mg/g for Pb(II), Cd(II), Cu(II) and Co(II), respectively. It is
      the first time that such a high loading capacity for Co(II) has been reported.
      The effect of the presence of chloride or sulphate was dependent on the nature of
      the cation. Lead(II) adsorption was endothermic in nature with increased
      randomness at the solid-liquid interface, while for the rest of the three cations
      the adsorption process was exothermic. The XRD and FTIR studies on the loaded
      samples revealed structural changes during the adsorption process. The high
      cation loading capacities along with the stability of the loaded adsorbent make
      the synthesized ferrihydrite-Fe2O3 nano powder a potential candidate for
      contaminated water purification.

PMID- 22988634
TI  - Biodegradation of nonylphenols using nitrifying sludge, 4-chlorophenol-adapted
      consortia and activated sludge in liquid and solid phases.
AB  - The biodegradation of a technical mixture of nonylphenols (tNP) with three
      different biomasses (nitrifying sludge, 4-chlorophenol-adapted consortia and
      activated sludge) was evaluated in batch tests. The tNP degradation was
      determined in solid and liquid phases. The three biomasses studied were able to
      biodegrade the technical mixture of nonylphenols. It was found that 33% to 44% of
      the initial tNP was adsorbed on to the sludge after 250 h. Nitrifying sludge
      presented the highest biodegradation percentage (43.1% +/- 2.3%) and degradation
      rate (3.10 x 10(-3) micromol/d). Acclimated 4-chlorophenol and activated sludge
      degraded 34.3% +/- 1.2% and 18.2% +/- 0.5% of the initial tNP, respectively.
      Actual half-life times of 10.9, 12.0 and 22.8 days were obtained for the
      biodegradation of tNP by nitrifying, acclimated 4-chlorophenol and activated
      sludge, respectively. It was concluded that, although nitrifiying biomass posses
      a high initial adsorption rate, this biomass can also biodegrade the tNP faster
      than the other tested biomasses.

PMID- 22988635
TI  - Phenol biodegradation by a microbial consortium: application of artificial neural
      network (ANN) modelling.
AB  - In this study, an effective microbial consortium for the biodegradation of phenol
      was grown under different operational conditions, and the effects of phosphate
      concentration (1.4 g L(-1), 2.8 g L(-1), 4.2 g L(-1)), temperature (25 degrees C,
      30 degrees C, 35 degrees C), agitation (150 rpm, 200 rpm, 250 rpm) and pH (6, 7,
      8) on phenol degradation were investigated, whereupon an artificial neural
      network (ANN) model was developed in order to predict degradation. The learning,
      recall and generalization characteristics of neural networks were studied using
      data from the phenol degradation system. The efficiency of the model generated by
      the ANN was then tested and compared with the experimental results obtained. In
      both cases, the results corroborate the idea that aeration and temperature are
      crucial to increasing the efficiency ofbiodegradation.

PMID- 22988636
TI  - Evaluation of pretreatments for inhibiting bromate formation during ozonation.
AB  - This study compared several pretreatment methods for inhibiting BrO3(-) formation
      during ozonation of tap water, from the DTU (Technical University of Denmark)
      campus, including H2O2 addition (peroxone), pH depression, and NH4+ and Cl2/NH4+
      addition. At the same time, the inhibition of atrazine and carbamazepine removal
      was evaluated for each pretreatment. The required delivered O3 dose to achieve
      90% removal of atrazine in the tap water from the DTU campus was 3.5 mg/L, which
      produced 130-170 microg/L BrO3(-). Peroxone did not reduce the required O3 dose
      for contaminant removal; however, it limited BrO3(-) formation to below the
      drinking water limit of 10 microg/L. Depression of solution pH to 6.0, reduced
      BrO3(-) formation to half, but it was still well above the water limit.
      Pretreatment with NH4+ also reduced BrO3(-) formation by approximately 50%,
      though it reduced atrazine degradation to 65%. Pretreatment with Cl2/NH4+ reduced
      BrO3(-) formation close to the 10 microg/L limit; however, atrazine removal did
      not exceed 75%. Carbamazepine was completely removed under all the tested
      experimental conditions with the 3.5 mg/L O3 dose.

PMID- 22988637
TI  - Effect of oligochaete worm body fluids on biological phosphorus removal in a
      bench-scale EBPR system.
AB  - During waste sludge reduction by oligochaetes, phosphorus (P) concentrations in
      the effluent have been noticed to increase. In the current study, batch
      experiments were carried out in order to provide explanations for this phosphorus
      release. The results indicated that increase in effluent phosphorus concentration
      might not be directly linked to the phosphorus in worm body fluids, as the
      phosphorus concentration in the system at the start of each operational period
      did not change significantly. However, the phosphorus removal efficiency rapidly
      dropped from 93.9% +/- 1.9% to 62.2% +/- 1.3% with increasing addition
      ofoligochaete worm body fluids. Furthermore, an increase in worm body fluids
      induced a remarkable enhancement ofanaerobic phosphorus release rate as well as
      anaerobic storage of poly-beta-hydroxyalkanoate (PHA). At a worm density (wet
      weight) of 14.4 g/L, the anaerobic phosphorus release rate was elevated by 31.1%
      +/- 2.8% and 57.3% +/- 4.6% at 2.5% and 5.0% worm death rate, respectively,
      compared with the control. The contribution of worm body fluids to PHA production
      was 39.3-67.7 mg/g of dead worm (wet weight), which was mainly attributed to the
      extra synthesis of poly-beta-hydroxyvalerate (PHV). Unfortunately, in the
      concomitant aerobic stage, inhibition of 3-hydroxybutyric acid (PHB) oxidation
      and ammonia utilization was observed along with the increasing addition of worm
      body fluids. Meanwhile, nitrite elevation was found at the beginning of the
      aerobic stage, which might be negative to the aerobic metabolic processes
      performed by phosphate-accumulating organisms (PAOs), namely PHB oxidation,
      phosphate uptake and ammonia utilization for biomass growth.

PMID- 22988638
TI  - In-storage psychrophilic anaerobic digestion: acclimated microbial kinetics.
AB  - In-storage psychrophilic anaerobic digestion develops by microbial acclimation in
      covered swine-manure storage tanks, producing CH4 and stabilizing organic matter.
      To optimize the system's performance, the process kinetics must be understood.
      The objective of this study was to evaluate kinetic parameters describing the
      major stages in the digestion process, and to investigate the effect of
      temperature acclimation on these parameters. Specific activity tests were
      performed using manure inocula and five substrates at three incubation
      temperatures. Extant substrate activities were determined analytically for each
      case, and intrinsic kinetic parameters for glucose uptake were estimated by grid
      search fitting to the Monod model. The results demonstrate that this acclimated
      microbial community exhibits different kinetic parameters to those of the
      mesophilic communities currently modelled in the literature, with increased
      activity at low temperatures, varying with substrate and temperature. For
      glucose, the higher uptake is accompanied by lower microbial yield and half
      saturation constant. Decomposing these values suggests that active psychrophilic
      and mesophilic microbial populations co-exist within the community. This work
      also confirms that a new method of assessing microbial substrate kinetics must be
      developed for manure microbial communities, separating microbial mass from other
      suspended organics.

PMID- 22988639
TI  - A multi-technique approach for the quantification of Microcystis aeruginosa FACHB
      905 biomass during high algae-laden periods.
AB  - A pronounced dominance of toxic cyanobacteria has been found in eutrophic water
      bodies, with Microcystis being a common species. Although toxic cyanobacteria are
      commonly described worldwide, few recent papers on the sensitive and effective
      quantification of cyanobacteria have been published. In this paper, a multi
      technique approach was applied by the use of cell density counting, cell
      viability testing, chlorophyll a determination, microcystin monitoring and gene
      extraction techniques to quantitatively analyse the cyanobacterial biomass of
      Microcystis aeruginosa FACHB-905. The entire dataset was used to examine the
      relationships between these indices. Results showed that, for 10(7) viable cells
      in the experimental conditions, the contents of chlorophyll a, microcystin-LR and
      total genes (16S rDNA) averaged 2.65 microg, 0.61 microg and 0.79 microg,
      respectively. For different cell viability proportions in the same particular
      phase of growth, it is easy to obtain the respective amount of viable cells and
      inactive cells and their measurable indices when any one of the three indices,
      chlorophyll a, DNA or microcystin-LR, is measured. This study provides a new
      perspective and method for determining multiple indices of toxic cyanobacteria
      during the same conditions and phases.

PMID- 22988640
TI  - Grain type and size of particulate matter from diesel vehicle exhausts analysed
      by transmission electron microscopy.
AB  - The aim of this research was to apply a simple and quick method of size and shape
      characterization by TEM to diesel exhaust particles from large-capacity, high
      performance trucks. Particulate matter (PM) samples were collected while the
      engines were idling. Investigation of this type of emission is essential because
      vehicles are idling at stop lights, in traffic, or during slow movement, goods
      loading and unloading. In these conditions, PM emission cumulates in a small
      area. It was found that PM from vehicle exhaust emissions can be divided into
      three groups: soot, irregular-shaped particles and circular particles. Irregular
      shaped particles and soot aggregates were present in the exhausts of the three
      types of vehicle tested. Circular particles were identified only in the samples
      collected from exhaust emissions from the MAN vehicle, and were present in small
      amounts. The average surface area was in the range of 0.06 microm2 to 0.24
      microm2. Mean perimeter fluctuated from 2.09 microm to 4.14 microm, and Feret
      diameter from 0.21 microm to 0.31 microm. Circularity was in the range of 0.12 to
      0.30. Aspect ratio was around 0.30 to 0.45. Feret diameter seems to be a good
      parameter to define the mean size of particles, but does not take into account
      the influence of the shape. Therefore, this measurement seems to be useful just
      in the case of spherical or very rounded particles, not for all diesel PM. Thus,
      it is necessary to consider circularity or aspect ratio for DPM characterization.

PMID- 22988641
TI  - Physicochemical and thermal characteristics of the sludge produced after
      thermochemical treatment of petrochemical wastewater.
AB  - The present work describes the physicochemical and thermal characteristics of the
      sludge generated after thermochemical treatment of wastewater from a
      petrochemical plant manufacturing purified terephthalic acid (PTA). Although
      FeCl3 was found to be more effective than CuSO4 in removing COD from wastewater,
      the settling and filtration characteristics of FeCl3 sludge were poorer. Addition
      of cationic polyacrylamide (CPAA; 0.050kg/m3) to the FeCl3 wastewater system
      greatly improved the values of the filter characteristics of specific cake
      resistance (1.2 x 10(8) m/kg) and resistance of filter medium (9.9 x 10(8) m(-1))
      from the earlier values of 1.9 x 10(9) m/kg and 1.7 x 10(8) m(-1), respectively.
      SEM-EDAX and FTIR studies were undertaken, to understand the sludge structure and
      composition, respectively. The moisture distribution in the CuSO4 sludge, FeCl3
      sludge and FeCl3 + CPAA sludge showed that the amount of bound water content in
      the CuSO4 and FeCl3 + CPAA sludges is less than that of the FeCl3 sludge and
      there was a significant reduction in the solid-water bond strength of FeCl3 +
      CPAA sludge, which was responsible for better settling and filtration
      characteristics. Due to the hazardous nature of the sludge, land application is
      not a possible route of disposal. The thermal degradation behaviour of the sludge
      was studied for its possible use as a co-fuel. The studies showed that
      degradation behaviour of the sludge was exothermic in nature. Because of the
      exothermic nature of the sludge, it can be used in making fuel briquettes or it
      can be disposed of via wet air oxidation.

PMID- 22988642
TI  - Performance evaluation of cigarette filter rods as a biofilm carrier in an
      anaerobic moving bed biofilm reactor.
AB  - Biocarriers are an important component of anaerobic moving bed biofilm reactors
      (AMBBRs). In this study, the capability of cigarette filter rods (CFRs) as a
      biocarrier in an anaerobic moving bed biofilm reactor was evaluated. Two similar
      lab-scale anaerobic moving bed biofilm reactors were undertaken using Kaldnes-K3
      plastic media and cigarette filter rods (wasted filters from tobacco factories)
      as biofilm attachment media for wastewater treatment. Organic substance and total
      posphours (TP) removal was investigated over 100 days. Synthetic wastewater was
      prepared with ordinary water and glucose as the main sources of carbon and
      energy, plus balanced macro- and micro-nutrients. Process performance was studied
      by increasing the organic loading rate (OLR) in the range of 1.6-4.5 kg COD/m3 x
      d. The COD average removal efficiency were 61.3% and 64.5% for AMBBR with
      cigarette filter rods (Reactor A) and AMBBR with Kaldnes plastic media (Reactor
      B), respectively. The results demonstrate that the performance of the AMBBR
      containing 0.25 litres of cigarette filters was comparable with a similar reactor
      containing 1.5 litres of Kaldnes plastic media. An average phosphorus removal of
      67.7% and 72.9% was achieved by Reactors A and B, respectively.

PMID- 22988643
TI  - Experimental study on removal of NO using adsorption of activated
      carbon/reduction decomposition of microwave heating.
AB  - Experimental studies were carried out on flue gas denitrification using activated
      carbon irradiated by microwave. The effects of microwave irradiation power
      (reaction temperature), the flow rate of flue gas, the concentration of NO and
      the flue gas coexisting compositions on the adsorption property of activated
      carbon and denitrification efficiency were investigated. The results show that:
      the higher of microwave power, the higher of denitrification efficiency;
      denitrification efficiency would be greater than 99% and adsorption capacity of
      NO is relatively stable after seven times regeneration if the microwave power is
      more than 420 W; adsorption capacity of NO in activated carbon bed is 33.24 mg/g
      when the space velocity reaches 980 per hour; adsorption capacity declines with
      increasing of the flow rate of flue gas; the change in denitrification efficiency
      is not obvious with increasing oxygen content in the flue gas; and the maximum
      adsorption capacity of NO was observed when moisture in flue gas was about 5.88%.
      However, the removal efficiency of NO reduces with increasing moisture, and
      adsorption capacity and removal efficiency of NO reduce with increasing of SO2
      concentration in the flue gas.

PMID- 22988644
TI  - Full-scale in-line hydrolysis and simulation for potential energy and resource
      savings in activated sludge--a case study.
AB  - The potential effects of altering primary settlers during biological in-line
      hydrolysis and converting a nitrifying activated sludge process into a partial
      pre-denitrification process for the purpose of resource conservation were
      evaluated. A full-scale primary sludge hydrolysis experiment was performed at a
      wastewater treatment plant and implemented in a dynamic modelling tool based on
      ASM2d. The full-scale hydrolysis experiment achieved a volatile fatty acid (VFA)
      production of 43 g COD(HAc) x m(-3) with no release of ammonium. Additional
      nitrogen removal of 44 t N x a(-1) was simulated, and the produced hydrolysate
      was able to replace 50% of the annual ethanol usage. Furthermore, 196 MWh of
      electricity per annum could be saved through the reduction of ethanol production
      and the optimization of the operation strategy of the activated sludge tank by
      operating a different number of anoxic zones.

PMID- 22988645
TI  - Is it acne or is it rosacea? An important distinction.

PMID- 22988646
TI  - What is your diagnosis? Demodex folliculitis.

PMID- 22988647
TI  - Dermatopathology diagnosis: junctional epidermolysis bullosa.

PMID- 22988648
TI  - Nonpseudomonal ecthyma gangrenosum associated with methicillin-resistant
      staphylococcus aureus infection: a case report and review of the literature.
AB  - Ecthyma gangrenosum (EG) is a skin infection that is classically associated with
      Pseudomonas aeruginosa septicemia in immunocompromised patients. Other bacterial,
      viral, and fungal pathogens also have been implicated in EG. Both bacteremic and
      nonbacteremic forms of EG have been described. We describe a case of EG
      associated with methicillin-resistant Staphylococcus aureus (MRSA) in a 35-year
      old woman with acute lymphoblastic leukemia (ALL) and review the literature.

PMID- 22988649
TI  - Whey protein precipitating moderate to severe acne flares in 5 teenaged athletes.
AB  - Acne vulgaris has been linked to milk ingestion, both whole and skim milk. The
      milk fraction that promotes acne is unknown. Five case reports are presented of
      male patients aged 14 to 18 years who experienced onset of acne shortly after
      initiation of whey protein supplementation; 3 teenagers used the supplement for
      muscle building in football training and the other 2 for attempting to gain
      weight. All 5 patients had poor response to acne treatment regimens of oral
      antibiotics, topical retinoids, and benzoyl peroxide. Lesions fully cleared in 4
      patients after discontinuation of whey protein supplementation, but 1 patient's
      acne flared after reinitiation of the whey protein supplement. Two patients did
      not immediately discontinue whey protein supplementation; 1 of them cleared after
      he discontinued whey protein during his second course of isotretinoin and 1 was
      lost to follow-up. Among these patients, at least 6 different brands of whey
      protein supplementation had been used, including whey protein shakes and
      reconstituted powders. Whey protein may be the fraction of dairy products that
      promote acne formation. Larger studies are needed to determine the mechanism of
      comedogenesis.

PMID- 22988650
TI  - Finasteride in the treatment of female pattern (androgenic) alopecia: a case
      report and review of the literature.
AB  - We describe a case of a 44-year-old woman with biopsy-proven female androgenic
      alopecia (FAGA), or female pattern alopecia, who was nonresponsive to topical
      minoxidil. After careful consideration and discussion with the patient, the
      decision was made to introduce oral finasteride 1.25 mg daily. After only 3.5
      months of therapy there was a remarkable reduction in hair shedding and increased
      hair regrowth without any reported side effects. We also present a comprehensive
      review of the limited studies and case series that have reported finasteride use
      for FAGA.

PMID- 22988651
TI  - Acneiform eruptions induced by epidermal growth factor receptor inhibitors:
      treatment with oral isotretinoin.
AB  - The most common cutaneous side effects to epidermal growth factor receptor (EGFR)
      inhibitors are follicular or acneiform eruptions, nail disorders, xerosis, and
      desquamation. Although topical and oral antibiotics with or without topical
      corticosteroids usually are safe and effective treatment options for acneiform
      eruptions due to EGFR inhibitors, they are not always successful in refractory
      cases. We report 3 cases of severe acneiform eruptions induced by EGFR inhibitors
      that were successfully treated with oral isotretinoin. Complete response was
      observed in all 3 patients. We recommend oral isotretinoin for the management of
      acneiform reactions to EGFR inhibitors when the lesions persist or worsen despite
      antibiotic treatment.

PMID- 22988652
TI  - Combined oral contraceptives for the treatment of acne: a practical guide.
AB  - Many therapies exist in the arsenal of drugs available to dermatologists for the
      treatment of acne vulgaris. Among them, hormonal therapy stands out as a unique
      and highly efficacious treatment modality. Although some dermatologists may be
      hesitant to prescribe hormonal therapies, they can be safely and appropriately
      used in eligible female patients to treat acne vulgaris. Herein, current issues
      regarding the hormonal treatment of acne in the form of combined oral
      contraceptives (COCs) are presented, and a practical method for implementing this
      therapy is proposed. Specifically, drug selection, associated risks, benefits,
      monitoring, and counseling are discussed, with emphasis on the practicality of
      use in the clinical setting.

PMID- 22988653
TI  - Randomized, observer-blind, split-face study to compare the irritation potential
      of 2 topical acne formulations over a 14-day treatment period.
AB  - This randomized, observer-blind, split-face study assessed the irritation
      potential and likelihood of continued use of clindamycin phosphate 1.2%--benzoyl
      peroxide (BPO) 2.5% gel or adapalene 0.1%--BPO 2.5% gel once daily over a 14-day
      treatment period in 21 participants (11 males; 10 females) with acne who were 18
      years or older. Investigator clinical assessment (erythema and dryness) and self
      assessment (dryness and burning/stinging) were performed at baseline and each
      study visit (days 1-14) using a 4-point scale (O = none; 3 = severe).
      Transepidermal water loss (TEWL) and corneometry measurements were performed at
      baseline and days 3, 5, 7, 9, 11, and 14. Lesions were counted at baseline and on
      day 14. Participant satisfaction questionnaires were completed on days 7 and 14.
      At the end of the study, investigators reported none or only mild erythema in 86%
      (18/21) of participants treated with clindamycin phosphate 1.2%--BPO 2.5% gel
      compared with 62% (13/21) of participants treated with adapalene 0.1%--BPO 2.5%
      gel. No severe erythema was reported with clindamycin phosphate 1.2%--BPO 2.5%
      gel. Adapalene 0.1%--BPO 2.5% gel was prematurely discontinued due to severe
      erythema in 1 participant on day 5 and a second participant on day 9.
      Additionally, 2 more participants reported severe erythema on day 14. Mean
      erythema scores were 0.9 (mean change from baseline, 0.7) with clindamycin
      phosphate 1.2%--BPO 2.5% gel and 1.4 (mean change from baseline, 1.3) with
      adapalene 0. 1%--BPO 2.5% gel on day 14 (P < .05 for days 6-14). Similar results
      were seen with dryness. Mean scores were 0.5 (mean change from baseline, 0.4) and
      1.0 (mean change from baseline, 1.0), respectively (P < .05 for days 6-14). Self
      assessment, TEWL, and corneometry results underscored the investigator clinical
      assessment. Participant preference and likelihood of continued usage was greater
      with clindamycin phosphate 1.2%--BPO 2.5% gel. Continued use and efficacy results
      for the treatment of acne were influenced by the potential of the product to
      cause irritation and the participant preferences. Irritation potential was more
      pronounced and severe with adapalene 0.1%--BPO 2.5% gel. Undoubtedly, as a result
      more participants preferred treatment with clindamycin phosphate 1.2%--BPO 2.5%
      gel and were more likely to continue to use the product.

PMID- 22988654
TI  - Antipruritic hydrogel for the treatment of atopic dermatitis: an open-label pilot
      study.
AB  - Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in
      industrialized nations. The efficacy and tolerability of Atrapro (RD047-26)
      antipruritic hydrogel was evaluated in 17 adult participants with mild to
      moderate AD with associated pruritus. The antipruritic hydrogel was applied 3
      times daily to the affected areas of the body, and participants were evaluated on
      days 3, 7, and 14 (end of study). There were 3 efficacy end points: investigator
      global assessment (IGA), investigator pruritus assessment (IPA), and participant
      itch assessment (PIA). All 3 efficacy end points were met and showed a
      statistically significant improvement in the mean score from baseline to day 14
      (P < .001). The mean IGA score improved 43% from a baseline score of 2.7 to a day
      14 score of 1.53 (P < .001) on a 5-point scale (0 = clear; 4 = severe). The
      severity of pruritus decreased in 88% (15/17) of participants from baseline to
      day 14 based on the IPA and 82% (14/17) of participants based on the PIA. Most
      participants (82% [14/17]) experienced relief from itching by day 3, and this
      improvement remained consistent at each of the follow-up office visits. The only
      adverse event (AE) was mild postapplication skin dryness, which was reported by
      59% (10/17) of participants and resolved with increased use of emollients. Based
      on these promising results, further research on the antipruritic hydrogel is
      warranted.

PMID- 22988655
TI  - Minding MDS accuracy.

PMID- 22988656
TI  - Bridging the gap in dementia care.

PMID- 22988657
TI  - Culture and familiarity matter to elders.

PMID- 22988658
TI  - Plugged in.

PMID- 22988659
TI  - Honest apologies inspire trust.

PMID- 22988660
TI  - Do elderly edentulous patients with a history of periodontitis harbor periodontal
      pathogens?
AB  - OBJECTIVES: The presence of periodontal pathogens in the oral cavity may impact
      implant survival. Therefore, this study aimed to determine the prevalence of
      Campylobacter rectus, Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, Treponema
      denticola, Eikenella corrodens, and Parvimonas micra in a specific elderly
      population with a history of periodontitis who have never worn dentures. MATERIAL
      AND METHODS: Thirty dentate subjects (mean age 61.7 +/- 7.05 years) and 30
      edentulous subjects (mean age 65.8 +/- 8.05 years) were included in this cross
      sectional study. Microbiological samples of cheek mucosa and the dorsum of the
      tongue were taken from all subjects. In addition, sulcus samples were taken from
      the dentate group. All samples were analysed using a bacterial DNA-specific
      polymerase chain reaction. RESULTS: All the pathogens studied were detected in
      dentate and edentulous subjects. When cheek and tongue samples were combined, C.
      rectus, A. actinomycetemcomitans and E. corrodens presented with a similar
      prevalence in both groups, whereas the other species were more prevalent
      specifically in the dentate group (P<0.05). In dentate subjects, P. intermedia
      and T. denticola were present in higher frequencies in the cheek mucosa (26.67%
      and 66.67%, respectively), whereas P. gingivalis and T. forsythia were more
      prevalent in the tongue samples (26.67% and 56.67%, respectively). CONCLUSIONS:
      Periodontal pathogens may persist in the oral cavity of edentulous subjects who
      have had periodontal disease, even 1 year after the extraction of all teeth and
      in the absence of other hard surfaces in the mouth.

PMID- 22988662
TI  - Are you ready for the betel nut?
AB  - As Texas becomes more diverse in its urban populations, dentists should educate
      themselves on their diverse patient base, including its cultures and cultural
      habits. The betel nut is chewed by more than 10% of the world's population and
      the oral care of these patients present many unique challenges. Other cultural
      beliefs can represent years of ideas passed on from one generation to another and
      need to be respected. Education is an excellent way of changing harmful cultural
      habits.

PMID- 22988661
TI  - Oral and maxillofacial pathology case of the month. Palatal melanosis associated
      with imatinib mesylate therapy.

PMID- 22988663
TI  - Dentist-prescribed overnight bleaching is more effective than over-the-counter
      methods for vital tooth bleaching (UT CAT #557).

PMID- 22988664
TI  - Value for your profession: Answers to the most common credit-card processing
      questions.

PMID- 22988665
TI  - Changing the DNA of clinical care.

PMID- 22988666
TI  - Paging 'Dr. V'. Interview by Elizabeth Gardner.

PMID- 22988667
TI  - Medicare and private duty.

PMID- 22988668
TI  - Innovation opportunities for home health and hospice.

PMID- 22988669
TI  - Medicare beneficiaries and the future of the program.

PMID- 22988670
TI  - Medicare: past present and future. A conversation with Val J. Halamandaris.
      Interview by Lisa Yarkony.

PMID- 22988672
TI  - Romney picks Paul Ryan for VP.

PMID- 22988671
TI  - U.S. Supreme Court rules ACA constitutional: now what?

PMID- 22988673
TI  - A tribute to Senator Olympia Snowe.

PMID- 22988674
TI  - What's my role?

PMID- 22988675
TI  - Getting answers to your health coverage questions.

PMID- 22988676
TI  - 47 candles for Medicare.

PMID- 22988677
TI  - Putting elasticity in customer relationships.

PMID- 22988678
TI  - Delirium and dementia: can they coexist?

PMID- 22988679
TI  - A closer look at nutritional risk factors.

PMID- 22988680
TI  - Happy birthday Medicare!

PMID- 22988681
TI  - Clinical comparison of gluma and Er:YAG laser treatment of cervically exposed
      hypersensitive dentin.
AB  - PURPOSE: To compare the desensitizing effects of a glutaraldehyde-based
      desensitizing system (Gluma) and an Er:YAG laser treatment on cervically exposed
      hypersensitive dentin. METHODS: A total of 22 subjects (mean age: 39 +/- 13.7
      years; 15 females, 7 males) suffering from cervical dentin hypersensitivity was
      included in a prospective, split-mouth clinical study. The teeth were treated on
      one side of the mouth with the glutaraldehyde-based desensitizing system and on
      the other side with the Er:YAG laser. Sensitivity perception was recorded before
      treatment (baseline), during and immediately after treatment, after 1 week, 1
      month, 3 months and 6 months. The subjects were asked to rate the sensitivity
      experienced during air stimulation by placing a mark on a visual analogue scale
      (VAS). RESULTS: Both techniques showed an effective reduction of cervical dentin
      hypersensitivity. The subjects experienced equal improvements compared to their
      status before and 6 months after treatment with both methods (P<0.001).

PMID- 22988682
TI  - Anti-gingivitis effects of a novel 0.454% stabilized stannous fluoride dentifrice
      relative to a positive control.
AB  - PURPOSE: To compare the anti-gingivitis efficacy of a novel 0.454% stannous
      fluoride dentifrice to a commercially available positive control triclosan
      containing dentifrice in a population of adults with gingivitis. METHODS: This
      single-center, randomized and controlled, double-blind, parallel group, 2-month
      trial enrolled 200 adults with mild-to-moderate gingivitis. At baseline, pre
      treatment gingivitis levels were assessed with both the Lobene Modified Gingival
      Index (MGI) and the Gingival Bleeding Index (GBI). Subjects were randomly
      assigned to one of two test dentifrices: either 0.454% highly bioavailable
      stannous fluoride or the 0.30% triclosan positive control. Following at-home,
      unsupervised toothbrushing according to manufacturer's instructions with their
      assigned test dentifrice for 2 months, subjects were re-evaluated for gingivitis
      again via the MGI and GBI examinations. RESULTS: A total of 196 subjects
      completed the trial and were evaluable. At Month 2, both test dentifrices
      produced statistically significant reductions in number of bleeding sites, GBI,
      and MGI on average relative to pre-treatment (P< 0.0001). The Month 2 adjusted
      mean improvement from baseline for the stannous fluoride dentifrice group was 62%
      greater for number of bleeding sites, 60% greater for GBI, and 45% greater for
      MGI versus the triclosan/copolymer positive control group; groups differed
      significantly (P<0.0001) for each gingivitis measure at Month 2. Both dentifrices
      were well-tolerated.

PMID- 22988683
TI  - Secondary caries inhibition promoted by adhesive systems and bleaching agents
      with fluoride.
AB  - PURPOSE: To evaluate the initial caries development at adhesive/enamel interface
      after 10% carbamide peroxide bleaching (CP) with or without fluoride (F) under
      dynamic pH-cycling. METHODS: Standard cavities were prepared on the bucal surface
      of 60 bovine incisors, which were restored with two fluoride-containing
      adhesives: Optibond FL (FL) and Optibond Solo Plus (SP). The restored teeth were
      submitted to thermal cycling process in order to age the adhesive/enamel
      interface. Both SP and FL adhesive-restored teeth were divided into groups (n=
      10) and bleached with 10% CP (CP) and 10% CP + F (CPF) or remained unbleached
      (Control). Bleaching was performed for 14 days simultaneously with pH-cycling.
      The specimens were prepared for cross-section microhardness evaluation and
      polarized light microscopy analysis to evaluate caries lesions at different
      depths around the bonded interface. RESULTS: Group FL (not bleached) presented
      the lowest mineral loss rate among groups, but secondary caries formation was
      observed for all groups around the bonded interface. An inhibition zone was
      observed for all groups, with caries lesion detected at 5 microm from the cavity
      wall.

PMID- 22988684
TI  - Comparative efficacy of two treatment regimens combining in-office and at-home
      programs for dentin hypersensitivity relief: a 24-week clinical study.
AB  - PURPOSE: Dentin hypersensitivity is a significant clinical problem that affects
      numerous individuals. This sharp pain, arising from exposed dentin in response to
      external stimuli, can be a particularly uncomfortable and unpleasant sensation
      for patients, because it interferes with their quality of life. The objective of
      this 24-week, single-center, parallel group, double-blind, stratified and
      randomized clinical study was to evaluate the clinical efficacy of a single
      professional treatment with an in-office desensitizing paste followed by twice
      daily brushing with a desensitizing toothpaste and toothbrush for 24 weeks.
      METHODS: 100 adults with confirmed dentin hypersensitivity were randomly assigned
      into two groups. One group received a single in-office treatment with a
      desensitizing paste containing 8% arginine and calcium carbonate (marketed as
      Colgate Sensitive Pro-Relief Desensitizing Paste and Elmex Sensitive Professional
      desensitizing paste), after dental scaling, followed by 24 weeks of brushing
      twice daily with a desensitizing toothpaste containing 8% arginine, calcium
      carbonate with 1450 ppm fluoride as MFP (marketed as Colgate Sensitive Pro-Relief
      toothpaste and Elmex Sensitive Professional toothpaste) and using the Colgate
      Sensitive Pro-Relief toothbrush (Test Group). The other group received a single
      in-office treatment with Nupro-M pumice prophylaxis paste, after dental scaling,
      followed by 24 weeks of brushing twice daily with a non-desensitizing toothpaste
      containing 1450 ppm fluoride as MFP and with the Oral-B Indicator toothbrush
      (Negative Control Group). Hypersensitivity was reexamined immediately after in
      office product application and after 8 and 24 weeks of twice daily brushing.
      RESULTS: Immediately after professional product application, and after 8 and 24
      weeks, subjects assigned to the Test Group demonstrated statistically significant
      improvements in dentin hypersensitivity compared to subjects assigned to the
      Negative Control Group in tactile (49.8%, 57.5% and 32.9%, respectively) and air
      blast (26.0%, 38.4% and 34.3%, respectively) sensitivity scores. The instant
      reductions in dentin hypersensitivity provided by the single professional
      application of a desensitizing paste for in-office use, containing 8% arginine
      and calcium carbonate were maintained by twice daily brushing with the 8%
      arginine, calcium carbonate toothpaste with 1450 ppm fluoride as MFP and the
      Colgate Sensitive Pro-Relief toothbrush for at least 24 weeks.

PMID- 22988685
TI  - Laboratory bonding ability of a multi-purpose dentin adhesive.
AB  - PURPOSE: To evaluate the laboratory dentin and enamel microtensile bond strengths
      (microTBS) and interfacial ultra-morphology of a new multi-purpose dental
      adhesive applied under different bonding strategies. METHODS: microTBS - 36
      extracted caries-free human molars were assigned to six groups: Group CSE -
      Clearfil SE Bond, a 2-step self-etch adhesive (self-etch control); Group SBU-SE -
      Scotchbond Universal Adhesive (SBU), applied as a one-step self-etch adhesive;
      Group OSLm - OptiBond SOLO Plus (OSL), a 2-step etch-and-rinse adhesive applied
      on moist dentin (etch-and-rinse control); Group OSLd - OSL applied on air-dried
      dentin; Group SBU-ERm - SBU applied as a 2-step etch-and-rinse adhesive on moist
      dentin; Group SBU-ERd - SBU applied as a 2-step etch-and-rinse adhesive on air
      dried dentin. Build-ups were constructed with Filtek Z250 and cured in three
      increments of 2 mm each. Specimens were sectioned with a slow-speed diamond saw
      under water in X and Y directions to obtain bonded beams that were tested to
      failure in tension at a crosshead speed of 1 mm/minute. Statistical analyses were
      computed using one-way ANOVA followed by post-hoc tests at P< 0.05. Ultra
      morphologic evaluation - dentin-resin interfaces were prepared for each of the
      six groups, processed, and observed under a FESEM. RESULTS: microTBS - OSLm
      resulted in significantly higher mean microTBS (63.0 MPa) than the other five
      groups. All SBU groups ranked in the same statistical subset regardless of the
      dentin treatment. The lowest mean microTBS were obtained with CSE (47.2 MPa) and
      OSLd (50.2 MPa), which were ranked in the same statistical subset.
      Ultramorphologic evaluation - The two self-etch adhesives resulted in a similar
      ultra-morphology. Dried dentin did not preclude the formation of a hybrid layer
      with SBU-ERd, as opposed to OSLd.

PMID- 22988686
TI  - Effects of post surface treatments on the bond strength of self-adhesive cements.
AB  - PURPOSE: To evaluate whether fiber post surface conditioning techniques would
      influence the ultimate retentive strength of self-adhesive resin cements into the
      root canal. METHODS: 50 single-rooted premolars with one root canal were
      endodontically treated and prepared to receive a fiber post. Five groups were
      formed (n=10) according to the post surface pre-treatment performed: (1) Silane
      application (Monobond S) for 60 seconds; (2) 10% hydrogen peroxide application
      for 20 minutes; (3) Rocatec Pre; (4) Silicate/silane coating (DT Light SL Post);
      (5) No treatment (DT Light Post). Two self-adhesive resin cements (RelyX Unicem
      and MaxCem) were used as luting agents. The bonded specimens were stored up to 1
      month (37 degrees C and 100% humidity). The force required to dislodge the post
      (MPa) via an apical-coronal direction was measured with the push-out bond
      strength test (cross-head speed: 0.5 mm/minute until failure). Failure patterns
      were evaluated under SEM. Data was statistically analyzed with one-way ANOVA and
      Tukey tests (P< 0.05). RESULTS: No increase in the push-out bond strength values
      were observed for RelyX Unicem, independently from the post surface treatment
      performed. MaxCem attained higher bond strengths when luted to silanated posts.

PMID- 22988687
TI  - Clinical evaluation of an in-office desensitizing paste containing 8% arginine
      and calcium carbonate for relief of dentin hypersensitivity prior to dental
      prophylaxis.
AB  - PURPOSE: To evaluate the clinical efficacy of a professional prophylaxis paste
      containing 8% arginine-calcium carbonate in the reduction of dentin
      hypersensitivity used as a pre-procedural application compared to a commercially
      available prophylaxis paste. METHODS: This study was conducted at Jersey Shore
      University Medical Center in Neptune, New Jersey, USA. A mixed population of
      adult males and females between the ages of 18-70 were included in the study.
      Baseline air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity
      Scale) were mandatory for inclusion in this study. Subjects were randomly
      assigned to either: (1) Control paste, Nupro non-fluoridated pumice based
      prophylaxis paste (Dentsply Professional) or (2) Test paste, a desensitizing
      paste containing 8% arginine and calcium carbonate (Colgate-Palmolive Company).
      Either the Control or Test paste was applied to subjects prior to their receiving
      a routine dental prophylaxis. After completion of the dental cleaning procedure,
      a final post-cleaning air blast examination was performed on each subject
      following identical methods as at the baseline exam. Paired t-tests and ANCOVA
      were used. RESULTS: 66 subjects were enrolled in the study. Following the post
      cleaning air blast hypersensitivity examination, there was a significant decrease
      of 83.94% in the hypersensitivity of subjects using the Test paste. The group
      using the Control paste showed a 13.43% desensitization. There was a
      statistically significant difference of 79.65% between the two groups. Subjects
      in the age groups 41-50, 51-60, and 61-70 years of age showed the most reduction
      in dentin hypersensitivity.

PMID- 22988688
TI  - Quantification and identification of bacteria in acrylic resin dentures and dento
      maxillary obturator-prostheses.
AB  - PURPOSE: To quantify and identify bacteria detected in acrylic resin dentures and
      dento-maxillary obturator-prostheses after long-term use. METHODS: The internal
      layer of denture bases from 13 daily-use removable acrylic resin dentures was
      sampled, while the inner fluid samples/no-fluid samples of obturators were
      collected from 11 in-use acrylic resin dento-maxillary obturator-prostheses.
      Samples were cultured, and isolated bacteria were counted and identified by
      molecular biological methods. RESULTS: Bacteria were detected in five (38.5%)
      acrylic resin dentures and six (54.5%) acrylic resin obturators. Four
      Lactobacillus species and one Propionibacterium species were isolated from three
      repaired denture bases, and from two non-repaired dentures, two Actinomyces
      species and Streptococcus mutans were isolated. On the other hand, 17 bacterial
      species, belonging to the family and genera of Olsenella, Bacillus, Citrobacter,
      Enterobacteriaceae, Lactobacillus, Pantoea, Peptoniphilus, Klebsiella and
      Pseudomonas, were isolated from obturators. Several species of viable bacteria
      were detected in acrylic resin denture bases and obturators.

PMID- 22988689
TI  - Effect of adhesive resin application on the progression of cavitated and non
      cavitated incipient carious lesions.
AB  - PURPOSE: To evaluate the penetration of two different adhesive resin systems into
      cavitated and non-cavitated artificial carious lesions and the behavior of
      treated carious lesions under further acid attack. METHODS: Artificial caries
      like lesions were created on the proximal surface of 100 human primary molars by
      a demineralizing gel. The teeth were assigned to three groups according to the
      adhesive resin used. Group 1 (G1) was for Single Bond adhesive resin, Group 2
      (G2) for Xeno V adhesive resin, and Group 3 (G3) was without any adhesive
      application. Each group was randomly and equally subdivided into subgroups a and
      b. In subgroup a, the teeth were kept with intact artificial caries-like lesion
      surfaces while in the subgroup b, a minute cavity was made at the center of
      artificial caries-like lesions using a sharp explorer. Each tooth was sectioned
      occluso-cervically into two halves through the center of the lesion; the
      sectioned surface was polished and examined under a reflected light microscope
      for estimating the depth of the carious lesion or penetration of the adhesive
      resin. All tooth halves were coated at the sectioned surface with two layers of
      acid resistant nail varnish and returned again to the demineralizing solution to
      assess the progression or arrest of the carious lesion after the second acid
      attack. RESULTS: The penetration depth of adhesive resins did not differ
      significantly between subgroups (P>0.05). After the second acid attack, the
      infiltrated carious lesions showed no lesion progression while the non
      infiltrated lesions showed advanced caries progression.

PMID- 22988690
TI  - Contemporary adhesives: marginal adaptation and microtensile bond strength of
      class II composite restorations.
AB  - PURPOSE: To evaluate the marginal adaptation (in terms of % continuous margin)
      and microtensile bond strength (microTBS) of the enamel and dentin of direct
      class II composite restorations. METHODS: 32 standardized class II cavities were
      prepared with the gingival margin of one box occlusal to the cementum-enamel
      junction (CEJ) and one gingival floor extended beyond the CEJ. The teeth (n= 8)
      were restored using one of four adhesive systems [Adper Scotchbond Multi Purpose
      (SMPP), Adper Scotchbond 1 XT (S1XT), Clearfil SE Bond (CSEB), or Clearfil Tri-S
      Bond (CTSB)] with incrementally placed composite restorations before being stored
      in water (24 hours), thermocycled (2,000 cycles, 5 to 55 degrees C) and
      mechanically loaded (50,000 cycles, 50 N). Marginal adaptation was evaluated by
      SEM. Additionally, the teeth were sectioned and trimmed to obtain specimens for
      microTBS testing. RESULTS: All adhesive systems exhibited "continuous margins" in
      enamel over 95.4%, whereas "continuous margins" in dentin ranged from 60.2 to
      84.8%. CSEB and CTSB yielded significantly more "continuous margins" between the
      adhesive restoration and dentin than SMPP or S1XT (P< 0.05). The mean microTBSs
      (MPa) for enamel were 40.5 (SMPP), 37.3 (S1XT), 30.8 (CSEB) and 23.2 (CTSB), and
      for dentin, they were 37.7 (SMPP), 33.0 (S1XT), 37.3 (CSEB) and 29.0 (CTSB).

PMID- 22988691
TI  - DDS do-it-yourself.

PMID- 22988692
TI  - Considering renting space in an established office? Define terms to avoid
      complications.

PMID- 22988693
TI  - Cloud computing?

PMID- 22988694
TI  - Dr Craig A Mason. Interview by Bill Scheerer.

PMID- 22988695
TI  - 10 common management errors: mistakes dentists make--and the solutions.

PMID- 22988696
TI  - Are dental X-rays safe?

PMID- 22988697
TI  - Inner peace.

PMID- 22988698
TI  - Snacking ourselves sick.

PMID- 22988699
TI  - The gift that keeps on costing: a real-life story of a dentist's kind gesture
      gone sour.

PMID- 22988700
TI  - Do 5-ARIs have a role in preventing BPH?

PMID- 22988701
TI  - Early diagnosis improves survival in colorectal cancer.
AB  - Colorectal cancer is the second most common cause of death from cancer in the UK.
      Common alarm symptoms include rectal bleeding, change in bowel habit and iron
      deficiency anaemia. Abdominal mass, weight loss, nausea and vomiting, anorexia
      and abdominal swelling are less common presenting symptoms. Patients meeting the
      NICE criteria for urgent referral should be referred via the two week wait
      pathway to the local colorectal department for prompt assessment to exclude
      colorectal cancer. Colorectal cancer has a male predominance and is strongly
      associated with age; 80% of new cases occur in patients aged over 60. Obesity and
      limited exercise are strong risk factors. Diets low in fruit and vegetables and
      fibre and high in red meat have also been associated with an increased risk.
      Patients with one first-degree relative under 45 or two first-degree relatives of
      any age have an approximate lifetime risk of developing colorectal cancer of 16
      25% in men and 10-15% in women. Having one first-degree relative who developed
      the disease after the age of 65 barely increases lifetime risk. Patients with
      ulcerative colitis and Crohn's colitis also have an increased lifetime risk of
      colorectal cancer. In the NHS Bowel Cancer Screening Programme, patients are
      screened with a faecal occult blood test which they complete at home and return
      by post. Patients with positive tests are then offered further investigation,
      typically colonoscopy. The sensitivity of colonoscopy for detecting abnormalities
      is > 90% and hence it is the gold standard test for evaluating the large bowel.
      Once a diagnosis of colorectal cancer has been confirmed, the extent of disease
      is evaluated by a CT scan of the chest, abdomen and pelvis.

PMID- 22988702
TI  - Diagnosing and managing acute diverticulitis.
AB  - Diverticulosis is the most common structural abnormality of the colon and affects
      up to one third of those over the age of 60 years. Its complications account for
      more than 3,000 deaths per year. Acute diverticulitis is the most common
      complication and 10-25% of patients with diverticulosis may have one or more
      episodes. Patients present with left-sided abdominal pain that localises in the
      left iliac fossa. This left-sided pain reflects the underlying predominant left
      sided distribution of the diverticula on this side. Patients may also present
      with right-sided or suprapubic pain, caused either by right-sided diverticulosis
      or a redundant sigmoid loop lying toward the right side, which may mimic
      appendicitis. The pain may be associated with changes in bowel habit. Dysuria and
      frequency may occur if the inflamed segment of bowel is adjacent to the bladder.
      Patients should be assessed according to their level of pain and associated
      systemic features of sepsis. In those in whom the pain is controlled and there
      are no signs of systemic sepsis and no high-risk features the patient may be
      treated in primary care but for those with systemic features of sepsis or high
      risk features admission to hospital is required. The diagnosis of acute
      diverticulitis in all patients with a new presentation should be confirmed by CT
      scan on admission to hospital.

PMID- 22988703
TI  - Identifying patients at risk of type 2 diabetes.
AB  - At present there are nearly 3 million people with diabetes in the UK. It is
      predicted that this number will almost double by 2025. Nine out of ten of these
      individuals will have type 2 diabetes. It is estimated that one in seven adults
      have impaired glucose regulation and up to 12% of these will develop type 2
      diabetes each year. The impact of obesity on the development of type 2 diabetes
      cannot be overemphasised, with a 1 kg/m2 increase in BMI raising the risk of
      impaired fasting glycaemia by 9.5% and of developing new-onset type 2 diabetes by
      8.4%. A 1 cm increase in waist circumference increases the risks by 3.2% and 3.5%
      respectively. NICE advises using a validated risk assessment tool to identify
      patients at risk of diabetes. Risk factors used by such tools include: age;
      ethnicity; weight; first-degree relative with type 2 diabetes; low birthweight
      and sedentary lifestyle. Certain comorbidities increase the risk of type 2
      diabetes, these include: cardiovascular and cerebrovascular disease; polycystic
      ovary syndrome; a history of gestational diabetes; and mental health problems.
      The initial screening blood test could be a fasting plasma glucose, HbA1c, or an
      oral glucose tolerance test, according to WHO criteria. NICE recommends that high
      risk patients should be offered a programme encouraging them to undertake a
      minimum of 150 minutes of moderate intensity physical activity a week, gradually
      lose weight to reach and maintain a BMI within the healthy range, increase
      consumption of whole grains, vegetables, and other foods that are high in dietary
      fibre, reduce the total amount of fat in their diet and eat less saturated fat.

PMID- 22988704
TI  - Psoriasis.

PMID- 22988705
TI  - Should we rethink the way we practise?

PMID- 22988707
TI  - American Nurses Association House of Delegates approves organizational
      transformation.

PMID- 22988706
TI  - Colorado Appeals Court rules in support of governor's opt out.

PMID- 22988708
TI  - Nurses as leaders: needed now more than ever!

PMID- 22988709
TI  - Clinical RNs lead quality improvement.

PMID- 22988710
TI  - [Chronic complex diseases. A new medical model of a huge societal challenge ].

PMID- 22988711
TI  - [Diffuse large B cell lymphoma: management in 2012].
AB  - Diffuse Large B Cells Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma
      and comprises a large number of different entities with different clinico
      pathological characteristics. The role of positron emission tomography is
      essential during the initial staging and post treatment assessment, and
      potentially at early- or mid-treatment evaluation of response. First line therapy
      comprises immuno-chemotherapy with rituximab and different cytotoxic agents that
      differ for components, dosages and frequency of administration taking worldwide
      recognized pre-treatment prognostic variables into account. After relapse,
      peripheral blood stem cells transplantation remains the only chance of cure. This
      review attempts to summarize the current state of our knowledge by highlighting
      the leads pursued to further improve current therapeutic results.

PMID- 22988712
TI  - [Perspectives in the management of congestive heart failure].
AB  - Heart failure constitutes a major public health problem. Its incidence continues
      to grow and its prognosis remains poor. Therapeutic approach of chronic heart
      failure with left ventricular systolic dysfunction is well codified. Recommended
      medical treatment is presented with the description of the different therapeutic
      classes. Recent advances are discussed. New therapeutic targets are described.
      Optimization of recognized treatment and application to heart failure of drugs
      used for other indications are developed. Therapeutic approach of heart failure
      with preserved ejection fraction is tackled but stays far less well defined. Many
      studies concerning treatment of acute heart failure are ongoing.

PMID- 22988713
TI  - [Is there still a place for a dual blockade of the renin-angiotensin system in
      2012?].
AB  - The blockade of the renin-angiotensin system (RAS) improves the prognosis of
      patients with complications related to diabetes, hypertension or, in general,
      atherosclerosis. Several observational studies have suggested the use of a dual
      blockade of the RAS to benefit from a better cardiorenal protection. However,
      recent randomized controlled studies failed to demonstrate that a dual blockade
      exert a better protection than single blockade, but showed a higher risk for
      renal complications and hyperkalemia. To decrease the residual risk, other
      opportunities may be recommended such as reinforcement of low salt diet, use of
      supraphysiological dose of a monotherapy inhibiting the RAS (perhaps prescribed
      at the evening) or addition of an aldosterone antagonist. However, all these
      approaches, as dual therapy, may also increase the risk of hypotension and renal
      insufficiency and thus require to be used under strict medical supervision.

PMID- 22988714
TI  - [Interest of chronotherapy in arterial hypertension].
AB  - The interest of chronotherapy in the field of arterial hypertension is
      progressively rising, especially in treated hypertensive patients characterized
      by a small decrease of their blood pressure during the night, and therefore often
      presenting a high cardiovascular risk. There are more and more data showing that
      administration of one antihypertensive drug in the evening (and even aspirin) can
      improve the blood pressure control during the night and the day/night blood
      pressure pattern, and so can diminish the level of risk. The role of
      chronotherapy also emphasizes the interest of 24 h ambulatory blood pressure
      monitoring in the management of high risk hypertensive patients.

PMID- 22988715
TI  - [Use of oral glucose-lowering agents in patients with renal impairment].
AB  - People with chronic kidney disease (CKD) of stages 3-4 (creatinine clearance <50
      ml/min) represent 25-30% of type 2 diabetic patients, but the problem is often
      underrecognized or neglected in clinical practice. However, most of oral
      antidiabetic agents have limitations in case of renal impairment, either because
      they require a dose adjustment, or because they are contra-indicated for safety
      reasons. It is the case for metformin (risk of lactic acidosis) and for most
      sulfonylureas (risk of hypoglycaemia). New antidiabetic agents are better
      tolerated in case of CKD. However, the daily dose of dipeptidyl peptidase-4
      inhibitors should be adjusted (except for linagliptin). Concerning new inhibitors
      of renal SGLT2 cotransporters, they have a reduced efficacy and their safety
      remains to be demonstrated in presence of CKD.

PMID- 22988716
TI  - [Metabolic surgery: an increasing place in the management of diabetes].
AB  - Bariatric surgery becomes more and more important in the management of the obese
      patient with type 2 diabetes, especially in case of failure of medical
      approaches. Metabolic improvement results not only from weight loss and the
      subsequent reduction in insulin resistance, but also from modifications of
      digestive hormones (especially incretins) that contribute to promote insulin
      secretion. This new paradigm, moving from bariatric surgery to metabolic surgery,
      opens new perspectives. The present article briefly describes innovative surgical
      techniques focusing on endocrine and metabolic improvement rather than on weight
      loss, the preliminary results of metabolic surgery in patients with type 2
      diabetes and a body mass index <35 kg/m2 and, finally, some data regarding the
      surgical management of obese patients with type I diabetes not well treated with
      classical medical means.

PMID- 22988717
TI  - [Neurosciences and the mind-brain connection: treatment of depression].
AB  - Neuroscientists claim that thoughts and intentions result only from brain
      activity. It is illustrated by the ability to control a robotic arm only by
      thought. However although they have a biological support, emotions, ideas and
      intentions are perceived at another level of reality than synapses and
      neurotransmitters. The reduction of mind to brain (called monism) represents a
      categorical error. Psychiatric praxis relies on a dualistic (complementary)
      position regarding e.g. depression treatment. Antidepressants and psychotherapy
      have distinct impacts on cerebral metabolism measured by fMRI and different ways
      to modify emotions. The combination of these two therapies is indicated in case
      of severe depression.

PMID- 22988718
TI  - [Latest news on the anti-alzheimer's front].

PMID- 22988720
TI  - [Hospital gowns].

PMID- 22988719
TI  - [Avastin and Lucentis for macular degeneration].

PMID- 22988721
TI  - [Jean-Paul and the delicacy of general medicine].

PMID- 22988722
TI  - [Alcoholic liver disease: another neglected disease?].

PMID- 22988723
TI  - [Alcoholic steatohepatitis: what's new in 2012?].
AB  - Alcoholic liver disease is a spectrum of lesions, of which the most severe is
      alcoholic steatohepatitis (ASH). Recent European guidelines define alcoholic
      hepatitis as a clinical syndrome: the recent onset of jaundice and/or ascites in
      a patient with ongoing alcohol misuse. Next to infection, the most frequent
      aetiology is ASH, a histological diagnosis. In case of severe ASH, as defined by
      prognostic scores, a biopsy is needed to confirm the diagnosis. Non-severe forms
      of ASH may improve with interruption of alcohol abuse only; however survival of
      severe forms of ASH is improved by the association of corticosteroids and N
      acetylcysteine. In case of uncontrolled infection, pentoxifylline may be
      administered. The Lille score, measured at the 7th day of corticosteroid therapy,
      measures response to therapy and guides the total duration of treatment.

PMID- 22988724
TI  - [Coagulation and cirrhosis: new insight].
AB  - The liver plays a key role in coagulation as all clotting factors except for
      factor VIII are synthetized by hepatocytes. In cirrhotic patients, there is a
      decrease of clotting factors and a thrombocytopenia. Those parameters usually
      modify routine coagulation tests and may suggest that cirrhotic patients are at a
      higher risk of bleeding. However, studies have shown that these patients are
      rather at risk for thrombosis. The reason is a concomitant decrease of
      coagulation inhibitors factors that is not detected in routine laboratory
      coagulation tests. The coagulation system in cirrhotic patient is a balance of
      pro and anti-coagulants. This balance may be affected by co-factors such as renal
      failure or infection. Artificial correction of laboratory values by transfusion
      of blood products may be rather deleterious (e.g. volume overload, TRALI).

PMID- 22988725
TI  - [Gastrointestinal neuroendocrine tumors: pleomorphic and often ignored].
AB  - Although generally considered as rare, incidence of gastrointestinal
      neuroendocrine tumors (GI-NETs) is increasing. The general practitioner has thus
      to be familiar with the vast array of clinical presentations and the growing
      family of diagnostic tools that can be used. Symptoms can be related to their
      hormonal production, their local extent or a bleeding complication. The prognosis
      depends on the grade of tumor, its local extent at diagnosis and its
      localization. The diagnosis relies on radiologic, endoscopic and nuclear medicine
      strategies. In case of typical symptoms, a hormonal secretion should be sought.
      Treatment options are extensive and should be discussed in an interdisciplinary
      manner.

PMID- 22988727
TI  - [Fecal calprotectin: a diagnostic tool for inflammatory bowel disease].
AB  - Fecal calprotectin (FC) is a valid biomarker to discriminate with a good
      sensitivity and specificity the presence of mucosal lesions of the
      gastrointestinal tube (e.g. ulcers in the context of inflammatory bowel disease
      (IBD)) from functional disorders (e.g. irritable bowel syndrome). FC is not
      specific for IBD and can be elevated also in gastrointestinal infections,
      ischemic colitis or neoplasia. An elevated FC should stimulate further
      investigations, notably an endoscopic workup. The level of FC correlates with the
      endoscopic score in Crohn's disease and ulcerative colitis. The correlation of FC
      and the endoscopic severity is better than the one of CRP or blood leukocytes.
      Thus, FC can also be used in the follow-up of IBD patients.

PMID- 22988726
TI  - [Management of ascites due to portal hypertension].
AB  - Portal hypertension is regularly encountered by the general practitioner. It is
      defined by an elevation of the porto-systemic pressure gradient, with
      complications such as ascites, spontaneous bacterial peritonitis, hepatorenal
      syndrome, variceal bleeding, hypersplenism, hepatopulmonary syndrome or hepatic
      encephalopathy occuring when a significant elevation of this gradient is reached.
      Cirrhosis is the primary cause of portal hypertension in industrialized
      countries. Symptomatic portal hypertension carries a poor prognosis. Management
      should be initiated rapidly, including the identification and correction of any
      reversible underlying condition. Liver transplantation should be considered in
      advanced cases.

PMID- 22988728
TI  - [The role of probiotics in the treatment of inflammatory bowel diseases].
AB  - The intestinal mucosa is the site of a fundamental interaction between a large
      amount of foreign substances, the immune system and bacteria that colonizes the
      mucosa. Many gastrointestinal diseases are due to an altered interaction between
      all these actors, particularly inflammatory bowel diseases. As such probiotics
      (bacteria providing a benefit to the host) could provide an interesting solution
      as a therapeutic agent. The evidences supporting such use are limited but there
      are still some quality randomized controlled trials. The purpose of this review
      is to discuss the most recent evidences from the literature on the use of
      probiotics in the treatment of inflammatory bowel diseases.

PMID- 22988729
TI  - [Advanced practice nursing].

PMID- 22988730
TI  - [Down syndrome: diagnose or eradicate?].

PMID- 22988731
TI  - [A new form of West Nile virus. West Nile virus in Texas].

PMID- 22988732
TI  - [The deaths of Niel and Lance Armstrong].

PMID- 22988733
TI  - [Comparing premiums could be harmful to the truth].

PMID- 22988735
TI  - Japanese strategy for healthcare reform.

PMID- 22988734
TI  - Resumption of medical services after Great East Japan Earthquake.

PMID- 22988736
TI  - Implementing international patient safety goals.

PMID- 22988737
TI  - The issues and future of the healthcare delivery system in Japan.

PMID- 22988738
TI  - Main medical conditions of elderly Japanese in urban areas requiring long-term
      care: improving the focus of preventive care.
AB  - AIM: To improve preventive care administration, this paper epidemiologically
      categorized causative illnesses of frail Japanese elderly living in urban areas
      by age and sex. METHODS: Data from Japanese long-term care insurance (LTCI)
      documentation was used to categorize the patterns of disease incidence consisting
      of the main medical conditions and comorbid diseases among frail elders aged
      above 65 years (male: 193; female: 360) from the central area of Osaka
      prefecture. Logistic regression analysis was used to determine the diseases
      requiring intensive care: care level 3+. The fracture patients' ADL and cognitive
      functions were examined using the Cognitive Performance Scale (CPS). RESULTS: In
      the patterns of disease incidence, 43% of the men had lifestyle-related diseases,
      while 53% of the women had musculoskeletal disorders. The main medical conditions
      associated with care level 3+ in men were dementia (odds ratio, 5.4),
      cerebrovascular disease (CVD; 3.9), renal failure (8.9), and fracture and
      fracture sequelae (4.7); and in women, femoral fracture (42.7), CVD (8),
      vertebral fracture (6.2), dementia (4.4), and neoplasms (4.1). Further, 46% of
      the female patients with femoral fractures had dementia. CONCLUSIONS: Preventive
      measures should focus on lifestyle-related diseases, preventing dementia by early
      detection, treatment of hypertension and diabetes through medication, physical
      exercise and nutrition, and cancer screenings for both sexes, along with
      musculoskeletal disorders prevention for women. Since femoral fractures render
      patients (especially those over 80 years) bedridden with cognitive dysfunctions,
      fall prevention is essential.

PMID- 22988739
TI  - Laughter education for implementation of the smile-sun method to promote natural
      healing in public and healthcare facilities.

PMID- 22988740
TI  - Report on support activity for the East Japan Great Earthquake (May 27-29, 2011).
AB  - The M9.0 great earthquake that occurred on March 11, 2011 triggered a huge
      tsunami on the Pacific coast in the Tohoku region and caused enormous damage,
      resulting in 15,854 deaths and 3,276 missing persons (as of March 1, 2012,
      according to the Japanese National Police Agency). Presently, inhabitants in
      Fukushima Prefecture continue to live as refugees because of radiation
      contamination caused by explosions at the Fukushima nuclear power plants.
      Immediately after the earthquake, DMATs (Disaster Medical Assistance Teams) went
      to the affected areas to begin relief operations. The Japan Medical Association
      then founded the JMAT (Japan Medical Association Team), an organization to take
      over DMAT activities. The purpose of JMAT is (1) to assist hospitals and clinics
      in affected areas with daily care and (2) to provide medical care in refuge and
      aid stations. The Osaka Medical Association was assigned to be in charge of
      medical support in Iwate Prefecture. For medical services, team activities are
      more effective than individual efforts. Therefore, JMAT is basically a team
      composed of one doctor, two nurses, and one clerical officer. The team of Yao
      Municipal Hospital consists of two doctors, two nurses, two pharmaceutical
      chemists, and two office clerks. It is 13,000 km each way from Osaka to Iwate,
      and it is an estimated 15 hours by road. Our initial schedule was five days and
      four nights, leaving Osaka on the afternoon of May 26 and heading for Iwate on a
      chartered bus, engaging in medical care from the morning of May 27 to 30, leaving
      Iwate on the morning of May 30 and returning to Osaka that evening. However,
      since Hanamaki Airport in the inland area of Iwate Prefecture became usable
      starting in mid-May, we arrived in Hanamaki City by air and used a large taxi
      from the airport. In accordance with the recovery of local medical institutions,
      the Osaka Medical Association JAMT dispatch was to be terminated by the end of
      May. As a result, our team's itinerary was reduced to three days and two nights,
      leaving on the morning of May 27 (by air), and returning to Osaka on the evening
      of May 29 (by air).

PMID- 22988741
TI  - Stress coping ability in nursing students: studies on the influence factor of
      Sense of Coherence (SOC).
AB  - The researchers conducted an investigation on factors influencing stress coping
      ability, referred to as a Sense of Coherence (SOC). 278 students in the 2nd to
      4th year of "A" University nursing program were subjected to this survey, and the
      response rate was 75.5%. The average SOC value was 39.5 +/- 6.6 for males, and
      37.4 +/- 7.0 for females. The value for age group 20 to 24 years old was 37.1 +/-
      6.8. The average SOC value obtained through this survey was higher than the
      survey results of the Kanto region and lower than the national results. When a
      comparison was made between "the group with higher average SOC" and "the group
      with lower average SOC" among the entire survey average SOC, especially
      significant differences were discovered in the following items. "Prospects for
      the future is bright", "Difficult experiences have meaning", "I have good
      relationship with friends", "I feel stressed", and "I was seriously ill" (P <
      0.001). "I am always interested in other people", and "I have a friend to rely on
      in difficult circumstances" (P<0.01). "I can do most anything if I put my mind to
      it", "We can encourage each other", "I am satisfied with my current situation",
      "I was satisfied with my role in my club", and "I was able to enter my desired
      university" (P<0.05). The researchers categorized these items into 1) Positive
      meaning from a difficult experience, 2) Cognition to prevent stressor from
      becoming negative stress, 3) Experience of success, 4) Satisfaction and self
      confidence, 5) Sociability, and 6) Presence of a reliable other. It was
      discovered that offering environment where people can work hard together by
      learning from others is an important issue to improve SOC.

PMID- 22988742
TI  - [Development of scientific research and infrastructure as a part of the goals of
      the programme "pediatrics"].

PMID- 22988743
TI  - [Technological programme "pediatrics". Proposals and concepts of the programme
      events].

PMID- 22988744
TI  - [Scientific research and infrastructure of the programme "pediatrics"].

PMID- 22988745
TI  - [The presidium resolution on development of scientific researches and
      infrastructure as a part of the programme "pediatrics"].

PMID- 22988746
TI  - [World level of competitiveness of national researches in the field of clinical
      medicine].
AB  - There is proposed formalization of concepts ,world research levelb and "leading
      scientific technological directions" of global science used in program documents
      which define main trends of reformation of Russian science. Use of bibliographic
      index as an example of "normalized citation in related area" for analyzing
      various subject areas for Russian clinic medicine it was shown that there is a
      different correlation of some areas of some national subject areas to their world
      levels. It was noted that it's necessary to develop national methodology of
      Russian science audit considering its national aspect which is a real problem
      while application world-acclaimed methods.

PMID- 22988747
TI  - [Heme oxygenase-2 neurons brain and spinal cord of human].
AB  - Immune localization of heme oxygenase-2 in neurons of some nuclei of the spinal
      cord and brain stem in 6 men 18-44 years old who died from causes unrelated to
      injury of central nervous system was studied. Neurons with positive reaction are
      determined for all studied regions of the brain where their contents in various
      nuclei ranging from 0.5 to 16% of the total number of cells detected by methylene
      blue. In all the sensory nuclei there is a high proportion of small neurons with
      a high or moderate density of reaction produce deposits. Large cells of motor
      nuclei often exhibit negative or low intensive enzyme reaction.

PMID- 22988748
TI  - [Molecular mechanisms of development of cerebral tolerance to ischemia. Part 1].
AB  - In the first part of this review molecular mechanisms of ischemic tolerance
      emerging as a result ofpreconditioning of the brain are discussed. Data on
      inductors, sensors, transducers and effectors of early and delayed ischemic
      tolerance are presented.

PMID- 22988749
TI  - [Occupational risk management: prognosis, causation and bioinformational
      technologies].
AB  - Methodology of occupational risk management is outlined based on workers' health
      disorders forecast and causation (work-relatedness assessment). It originates
      from Labour Code of Russian Federation prescriptions and includes principles,
      methods and criteria of risk management and risk communication. The methodology
      is realized by means of bioinformational technologies as expert and analytical
      system in the form of interactive Web-based directory "occupational risk
      assessment" for practical use for occupational risk prevention.

PMID- 22988750
TI  - ['Translational medicine as a way from fundamental biomedical science to public
      health services].
AB  - Increasing distance between practical public health services and collecting of
      theoretical information in the field of biomedical researches reflects the
      necessity of professional contact between clinicians and scientists in many areas
      associated with medicine for active carrying over ("translation") of the modern
      basic researches in which mechanisms of basic metabolic processes and
      possibilities of their correction are detected, to effective medical help to
      individual patient, i.e., personified medicine. Such approach was called
      transmitting medicine. Examples of the personified medicine in which biomedical
      researches together with the anamnesis morbi of individual patient that are
      responsible for treatment strategy including doses and regimens are discussed.

PMID- 22988751
TI  - [Oxygen-transport function of blood at pregnant, transferred the aggravation of
      the herpesvirus infection].
AB  - Factors which may influence on erythrocytes in peripheral blood while
      exacerbation of herpes infection are studied. The data showed that herpes
      infection changed quantitative spectrum of proteins in erythrocytes. In cellular
      membranes of erythrocytes lipid peroxidation increases that results in increase
      of microviscosity of membranes. Disconnection of hemoglobin with 2, 3-DPhG was
      defined. This results in decreased hemoglobin oxygenation and change of
      erythrocytes form. The data showed that herpes virus in exacerbation leads to
      tissue hypoxia in pregnant women.

PMID- 22988752
TI  - [Endogenous opioid system as a mediator of acute and long-term adaptation to
      stress. Prospects for clinical use of opioid peptides].
AB  - It has been well established that opioid peptides (OPs) affect various hormonal
      systems. Opioids exhibit stress-limiting and gastro-protective effects in
      stressed animals, acting via mu- and delta-opioid receptors (OR). Peripheral mu
      OR stimulation by endogenous and exogenous opioids increases cardiac tolerance to
      pathological consequences of stress. Enhancement ofprostacyclin synthesis,
      decrease of thromboxane production as well as suppression of lipid peroxidation
      can be directly responsible for cardioprotective effects of OPs in stressed
      animals. Adaptive responses are accompanied by increased OP levels in blood and
      tissues. Reduction of ventricular arrhythmias induced by repeated short-term
      immobilization stress is mediated via mu-OR stimulation by endogenous opioids,
      while delta-OR account for an antiarrhythmic effect of adaptation to chronic
      intermittent hypobaric hypoxia. The mechanism of infarct size-limiting effect of
      continuous normobaric hypoxia involves both mu- and delta-OR stimulation. Peptide
      OR agonists can be considered in future clinical practice for treatment of
      withdrawal syndrome, stress-related cardiac disease or myocardial injury caused
      by ischemia-reperfusion insult.

PMID- 22988753
TI  - [Specific features of the melanophore system in different color morphs of larvae
      of the common toad (Bufo bufo L.)].
AB  - In a natural pond among usual black larvae of the common toad (Bufo bufo L.), a
      few unusual individuals of red-olive coloring were found out. In both morphs we
      investigated the melanophores of skin using different methods. The ESR
      spectrometric analysis has shown the absence of distinctions between morphs by
      the amount of melanin. Analysis of total preparations of skin has shown the
      presence of various kinds of melanophore cells both in the derma and in the
      epidermis. Among typical melanophores, essentially differing cells appeared
      (atypical cells). In black morph tadpoles, the number of all kinds of
      melanophores is significantly greater than in red-olive morphs. It is shown that
      dark coloring is connected with a considerable number of atypical cells in the
      epidermis imposed on a dense layer of typical dermal melanophores with dispersed
      melanin.

PMID- 22988754
TI  - [Evolutional principles of homology in regulatory genes of myogenesis].
AB  - Analysis of early steps in muscular system development of invertebrates and
      vertebrates shows that early steps of myogenesis are regulated by genes-orthologs
      mainly belonging to two families, Pax and bHLH. In the majority of the following
      organisms, muscles formation (steps of determination and the earliest steps of
      myogenesis) is regulated by genes orthologs Pax3 which belong to the family Pax:
      nematodes (Caenorhabditis elegans, Pristionchus pacificus), insects (Drosophila
      melanogaster), echinoderms (Strongylocentrotus purpuratus), sea squirts (Ciona
      intestinalis, Holocynthia roretzi), fishes (Danio rerio), amphibians (Xenopus
      laevis), birds, and mammals (mouse, rat). The nematode C. elegans is an exception
      since formation of its muscles in this period is regulated by homeobox gene Pal-1
      belonging to the family Caudal. The sea squirt C. intestinalis is also an
      exception because the earliest steps of development involved in further muscle
      formation are accompanied by activation of the gene CiSna (snail) (gene family
      basic Zinc finger). The next steps of myogenesis in all analyzed species are
      regulated by genes orthologs belonging to the family of transcriptional factors
      bHLH. They along with genes Pax3 are characterized by a high extent of homology
      in all studied groups of animals.

PMID- 22988755
TI  - [Phylogeography of red deer (Cervus elaphus): data of analysis of polymorphism of
      the mitochondrial gene for cytochrome b].
AB  - Analysis of polymorphism of the gene for cytochrome b (1140 bp) of 106 samples of
      red deer (Cervus elaphus) of Eurasia is carried out, and the phylogenetic
      relationships of groups throughout the entire geographic range, including North
      America, are reconstructed. In total, the paper describes 75 haplotypes, 33 of
      them for the European and 42 for the Asian part of the geographic range. Common
      haplotypes for these two parts of the range were not found. The genetic kinship
      of Asian Siberian stags and North American wapiti is confirmed. Red deer living
      in Yakutia are close to the Siberian stags of Altai and Tuva, whereas red deer
      that live in Krasnoyarsk krai and Irkutsk oblast form a separate group. Overall,
      the reconstructed phylogeographic structure of the species is significantly
      different from the accepted subspecies differentiation based on morphological
      characters.

PMID- 22988756
TI  - [Septicaemia of chironomid larvae (Diptera: Chironomidae) promoted by Bacillus
      cereus and B. thuringiensis].
AB  - Natural factors regulating the population of chironomids were studied. The
      bacteria Bacillus cereus were isolated from chironomids sampled from Kuyalnitskii
      Firth after epizooty of Chironomus sp., and bacteria Bacillus thuringiensis spp.
      israelensis (Bti) were isolated from dead larva of Chironomus plumosus sampled in
      the Sea of Azov (3-m depth). Bti were characterized by high insecticide activity
      on midges Anopheles messeae Fall., Aedes cireneus Mg., and Culex pipiens pipiens
      f. pipiens L.

PMID- 22988757
TI  - [Correspondence analysis and combination of molecular genetic and morphological
      data in zoological systematics].
AB  - A new algorithmic approach is proposed for correspondence analysis of different
      types of data in zoological systematics. The algorithm is tested on actual data.
      A high degree of correspondence is shown for morphometric and genetic distances
      in the tested set of species. Two directions of variation in both character
      spaces have clearly appeared. The first direction discriminates families; the
      second discriminates orders. The characters responsible for these differences
      have been revealed. After uniting both distance matrixes, the morphological one
      and the molecular genetic one, into a single matrix, and displaying the
      summarized distances between species on a plane, the configuration of species
      remained principally unchanged. The principal directions of variations were
      preserved and marked the differences between orders, families, and genera.

PMID- 22988758
TI  - [Functional features of microbial communities in the digestive tract of field
      voles (Microtus rossiaemeridionalis and clethrionomys glareolus)].
AB  - The nitrogen-fixating and cellobiohydrolase activity, the nitrogen (N) and carbon
      (C) contents, and the number of microorganisms in the prestomach, cecum, and
      colon of two vole species were studied: the southern vole (Microtus
      rossiaemeridionalis) and the bank vole (Clethrionomys glareolus), which is
      characterized by a mixed type of diet. The nitrogen-fixating activity in the
      cecum was found to be the highest in the voles compared with the mammals studied
      earlier. The seasonal dynamics of both nitrogenase and cellobiohydrolase
      activities was registered in the southern vole. The structure of the microbial
      complex in the southern vole is more varied and includes microorganisms
      associated with plant substrates.

PMID- 22988759
TI  - [Behavioral interactions of adult females of the common shrew (Sorex araneus)
      with conspecifics on familiar territory].
AB  - Interactions of overwintered females with conspecifics (> or = 5 days) on
      familiar territories were studied experimentally. In interactions of the resident
      females with unfamiliar overwintered females (28 experiments), there were no
      differences related to the reproductive status of both parties. Between the
      behavior of the residents and aliens, there were no significant differences,
      except the refusals of contacts--and aliens had more of it. Identification and
      affiliative behavior and the presence of ritualized aggression was noted. There
      was little direct aggression. Females were sharply aggressive toward the
      overwintered males (23 experiments) regardless of their reproductive status.
      Males tried to avoid contacts. Identification and affiliative behavior were rare.
      Toward yearlings (25 experiments), females that participated in reproduction were
      aggressive (direct aggression prevailed) and singles (9 experiments) were not.

PMID- 22988760
TI  - [Involvement of calmodulin in realization of vasoconstrictive effects of
      serotonin and norepinephrin].
AB  - Possible involvement ofcalmodulin in adrenergic and serotoninergic regulation of
      vascular contractility has been studied. Calmodulin inhibitors trifluoperazine
      and W-13 suppress vasoconstriction of the rat aorta in response to
      norepinephrine, serotonin, and serotonin 5HT1A- and 5HT2A-receptor agonists (8-OH
      DPAT and DOI, respectively) and do not affect the vasodilatory effect of 5HT1B-,
      5HT2B-, and 5HT4-receptors. The force of aorta contraction in response to 8-OH
      DPAT increases after the activation of calcium entry through voltage-gated Ca2+
      channels. This effect is not related to non-specific activation of alpha1
      adrenoceptors, since it is realized in the presence of prazosin. The inhibitor of
      calmodulin-dependent myosin light chain kinase KN93 decreases the
      vasoconstrictive response in response to norepinephrine and serotonin by only
      20%. Calmodulin inhibitors slightly decrease aortic constriction in response to
      endothelin-1, vasopressin, angiotensin II, and KCl. Trifluoperazine does not
      suppress vasoconstriction induced by the G-protein activator AlF4(-). It is
      assumed that the target of trifluoperazine and W-13 is calmodulin interacting
      directly with alpha1-adrenoceptors and serotonin 5HT1A- and 5HT2A-receptors.

PMID- 22988761
TI  - [The role of the floodplain gradient in structuring of testate amoebae
      communities in the Ilych River].
AB  - Forty-two testate amoebae taxa were identified in alluvial soils of floodplain
      islands in the Ilych River. Among the pedo- and eurybionts, there were aquatic
      rhizopods. Along the floodplain transect (willow --> meadow --> deciduous forest 
      -> coniferous forest), the testate amoebae community changed directly. There are
      spatially homogeneous (low beta-diversity) testacean communities but species rich
      on the local level (high alpha-diversity) within forests. Within willows and
      meadows, communities are characterized by low alpha-diversity and high
      heterogeneity that leads to high gamma-diversity.

PMID- 22988762
TI  - [Specific features of the numbers and structure of the population of
      Proteocephalus longicollis (Zeder 1800) (Cestoda: Proteocephalidea)--a mass
      parasite of whitefish Coregonus lavaretus L. under conditions of technogenic
      pollution of the water body].
AB  - The numbers, age structure, and morphological variation of the cestode
      Proteocephalus longicollis from whitefish of a natural water body (Kamennoe Lake)
      and those of Kostomuksha Lake polluted with wastes of the mining industry
      (Northern Karelia) have been studied. In the polluted water body, a high
      infestation of whitefish and domination of larval stages in the structure of the
      parasite population have been established. It is shown that under conditions of
      pollution, only one of the variations ofscolex signs dominates in the structure
      of phenotypic diversity. The size indices of cestodes are reliably smaller as
      compared with cestodes from the natural water body. The data obtained indicate
      that technogenic pollution determines a decrease in the intrapopulation diversity
      of P. longiocollis, and a decrease in the values of morphometric characters
      indicates inhibition of the morphophysiological state of individuals.

PMID- 22988763
TI  - [The mushroom bodies of the lower nematocera: a link between those of the higher
      Diptera and other mecopteroids].
AB  - Nematoceran Diptera are nonuniform in the structure of their mushroom bodies.
      Members of the more basal families (Ptychopteridae, Pediciidae, and Tipulidae)
      have bipartite mushroom bodies, characteristic of members of the other
      mecopteroid complex orders. In members of Bibionomorpha (Bibionidae and
      Anisopodidae), tripartite mushroom bodies have been found characteristic of
      Brachycera Orthorrhapha.

PMID- 22988764
TI  - [Geographic range of Callipogon relictus Semenov, 1899 (Coleoptera, Cerambycidae)
      in the Russian Far East].
AB  - Data on the distribution of Callipogon relictus Semenov, 1899 over the Russian
      Far East were generalized. The distribution map for C. relictus is based upon
      long-term observations and collection materials by the leading institutions. The
      chronology was studied within the Russian geographic range of the species.

PMID- 22988765
TI  - [Genetic diversity and evolution of the influenza C virus].
AB  - The influenza C virus is spread worldwide and causes diseases of the upper and
      (less frequently) lower respiratory tract in human. The virus is not pandemic,
      but it circulates together with pandemic influenza A and B viruses during winter
      months and has quite similar clinical manifestations. The influenza C virus is
      also encountered in animals (pigs and dogs) and is known to override the
      interspecific barriers oftransmssion. The immune system of mammals often fails to
      recognize new antigenic variants of influenza C virus, which invariably arise in
      nature, resulting in outbreaks of diseases, although the structure of antigens in
      influenza C virus in general is much more stable than those of influenza viruses
      A and B. Variability of genetic information in natural isolates of viruses is
      determined by mutations, reassortment, and recombination. However, recombination
      events very rarely occur in genomes of negative-strand RNA viruses, including
      those of influenza, and virtually have no effect on their evolution. Unambiguous
      explanations for this phenomenon have thus far not been proposed. There is no
      proof of recombination processes in the influenza C virus genome. On the
      contrary, reassortant viruses derived from different strains of influenza C virus
      frequently appear in vitro and are likely to be common in nature. The genome of
      influenza C virus comprises seven segments. Based on the comparison of sequences
      in one of its genes (HEF), six genetic or antigenic lineages of this virus can be
      distinguished (Yamagata/26/81, Aichi/1/81, Mississippi/80, Taylor/1233/47, Sao
      Paulo/378/82, and Kanagawa/1/76). However, the available genetic data show that
      all the seven segments of the influenza C virus genome evolve independently.

PMID- 22988766
TI  - [Inversion polymorphism and ecological specialization of malaria mosquitoes
      (Diptera, Culicidae) in Karelia].
AB  - The species composition and inversion polymorphism were studied in malaria
      mosquito larva hemipopulations of Karelia. Three malaria mosquito species-
      Anopheles messeae, A. beklemishevi, and A. maculipennis--were found in the
      region. The northern boundary of their range is at 65 degrees NL. The greatest
      species diversity was observed in biotopes of the central region. Within-species
      chromosome polymorphism was observed in larva populations of all three species.
      For A. messeae, maximum karyotype diversity indices were established for the
      southern and northern regions of Karelia.

PMID- 22988767
TI  - [Interspecific hybridization in the genus Paeonia (Paeoniaceae): polymorphic
      sites in transcribed spacers of the 45S rRNA genes as indicators of natural and
      artificial peony hybrids].
AB  - The ITS1-5.8S rDNA-ITS2 regions of 33 accessions belonging to 16 species and five
      natural and garden interspecific hybrids of the genus Paeonia L. were sequenced.
      Chromatograms of the peony hybrids demonstrated the presence of the signals,
      corresponding to two different nucleotides at the positions differing in the
      parents, indicating that in the hybrids, no rDNA isogenization usually occurred,
      and they preserved rDNA of both parents. Analysis of these polymorphic sites (PS)
      showed that P. x majkoae was interspecific hybrid between P. tenuifolia and P.
      caucasica. The ITS of P. hybrida differs from ITS of P. x majkoae in 19
      mutations. Because of this, P. x majkoae is definitely not synonymous to P.
      hybrida. Comparative analysis of ITS 1-5.8S rDNA-ITS2 showed that species
      diversity in section Paeonia was based on recombination as a result of
      intraspecific hybridization of three haplotype families. Specifically, haplotypes
      A, typical of the P. tenuifolia and P. anomala genomes, haplotypes B, typical of
      P. mlokosewitschii and P. obovata, and haplotypes of family C, currently
      represented in rDNA of diploid and tetraploid forms of some Caucasian and
      Mediterranean species. The ITS regions many diploid peonies contain no dimorphic
      sites, while P. oreogeton, P. cambessedesii, P. rhodia, and P. daurica carry from
      ten to 17 PS, and supposed to be the interspecific hybrids. Most of the
      tetraploid peonies contain from six to 18 PS in the ITS regions. These are
      alloploids with one of the parental genomes similar to that of P. mlokosewitschii
      (B1), or P. obovata (B3). The second parental genome in P. banatica, P.
      peregrina, and P. russii is represented by the genome, close to that of P.
      tenuifolia (A). P. macrophylla, P. mascula, P. coriacea, P. wittmanniana, and P.
      tomentosa carry genome of series B and genome of series C, which slightly
      resembles genome A.

PMID- 22988768
TI  - [Epigenetic variation of the choriflowered--symflowered character in the
      symflowered sugar beet line SOAN-14].
AB  - The effect of 5-azacytidine on the variation of the choriflowered (CF)
      symflowered (SF) character in sugar beet was studied in several generations
      obtained via seed reproduction. The epimutagen (5-azacytidine) significantly
      reduced the number of flowers in glomerate inflorescences in the year of seed
      treatment and in the next generation (Az1), leading to the appearance of plants
      with single flowers in bract axils of a flower stalk. The CF character resulting
      from epimutagene treatment of sugar beet seeds (plants with genotype M(Z)M(Z) was
      inherited as a monohybrid character in both zygotic and apozygotic seed
      progenies. The proportion of the CF and SF phenotypes in the progenies was
      affected bythe chromatid number in the chromosomes (mixoploidy of the cell
      populations). Alleles of the Mm locus were found to affect the variation in
      phytomere organization of flower stalks.

PMID- 22988769
TI  - [Phylogeography of the mallard Anas platyrhynchos from Eurasia inferred from
      sequencing of the mtDNA control region].
AB  - Phylogenetic relationships, demographic history, and geographic distribution of
      the mtDNA haplotypes of the mallard Anas platyrhynchos were examined in three
      populations, Indian, Northern European, and Far Eastern. Two divergent haplotype
      groups, A and B, were found in the Far Eastern population, while haplotypes
      identified in Northern European and Far Eastern populations were exclusively of
      the A group. The presence of B group haplotypes in the Far Eastern population can
      be explained either in terms of hybridization of the mallard with spot-billed
      duck Anas zonorhyncha at the south of the Russian Far East, or by the mtDNA
      paraphyly in mallards. In general, mallards from Eurasia were characterized by
      low genetic population differentiation along with slightly expressed
      phylogeographic structure. The most differentiated was the population from India
      (Phi(st) = 0.076-0.077), while the difference between Northern European and Far
      Eastern populations was extremely low (Phi(st) = 0.0029). Differentiation of Anas
      platyrhynchos Indian population was determined by the fact that a part of the
      population, inhabiting southern and eastern coasts of the Hindustan Peninsula,
      was resident.

PMID- 22988770
TI  - [Analysis of the mitochondrial DNA variation in pond smelt Hypomesus olidus
      (Osmeridae)].
AB  - Pond smelt Hypomesus olidus (Pallas, 1814), one of the five species of the genus
      Hypomesus, family Osmeridae, was examined for intraspecific variation of the
      mitochondrial DNA cytb (1062 bp) and COI (567 bp) genes. Among the ten single
      substitutions discovered, only one, leading to the substitution of isoleucine by
      valine, was nonsynonymous, while the remaining substitutions were synonymous. The
      degree of genetic divergence among pooled nucleotide sequences in H. olidus
      populations examined constituted 0.4% on average, ranging from 0.2 to 0.6%. These
      values were not higher than the levels of divergence between the individuals
      within the populations. Phylogenetic analysis of the populations examined did not
      reveal their subdivision depending of their geographic location, and pointed to
      the absence of intraspecific differentiation of the species.

PMID- 22988771
TI  - [Identification and classification of bovine leukemia virus isolates in Russia
      and Ukraine based on the pol viral gene polymorphism].
AB  - Bovine leukemia virus (BLV) is a widespread specific pathogen of cattle. Analysis
      of the pol viral gene polymorphism has been used to characterize the polymorphism
      of BLV isolates at stock-breeding farms in Russia and Ukraine. The fragments of
      the pol gene corresponding to the reverse transcriptase and integrase 494 and 233
      bp in size, respectively, have been used for analysis. Phylogenetic analysis has
      revealed several variants of BLV clustered with a high bootstrap support in
      Russia and Ukraine. A new classification of BLV variants is suggested. Comparison
      of phylograms based on the polymorphism of the nucleotide sequences of the
      integrase and reverse transcriptase domains did not show topological conflicts.
      Therefore, recombination between BLV variants has not been found.

PMID- 22988772
TI  - [Mutation p.E92K is the primary cause of cystic fibrosis in Chuvashes].
AB  - Molecular genetic study of the CFTR gene in cystic fibrosis patients from the
      Chuvash Republic is presented. We found linkage disequilibrium of the disease
      with 22-7-16-13 haplotype using intragenic markers. Major mutation p.E92K was
      revealed in chromosomes carrying this haplotype. The frequency of this mutation
      in Chuvash patients was 66.6%. Population study of the distribution of two
      mutations (p.E92K and F508del) of the CFTR gene revealed that their population
      frequency in heterozygous carriers was one per 37 subjects while calculated
      cystic fibrosis frequency in Chuvashia is one per 5420 newborns.

PMID- 22988773
TI  - [Crow's index and reproductive characteristic of the Republic of Tatarstan
      population].
AB  - On the basis of 1212 questionnaires filled up by women of postreproductive age
      living in five districts of the Republic of Tatarstan (Arsky, Atninsky,
      Kukmorsky, Buinsky, and Drozhzhanovsky), the basic reproductive characteristics
      and Crow's index and its components have been calculated. The rural population is
      characterized by expanded reproduction with a mean sibship size of 2.68; in
      district administrative centers, there is only simple reproduction. Crow's index
      and its components for the rural Tatar population are Im = 0.026, If = 0.172,
      Itot = 0.202. Graphic analysis of the mutual positions of some populations
      studied has been carried out.

PMID- 22988775
TI  - [New data on coat color mutant gene frequencies in domestic cats of the European
      part of Russia (the City of Kamyshin)].
AB  - Frequencies of mutant alleles that control coat color of domestic cats were
      determined in population of the city of Kamyshin, Volgograd oblast. Intermediate
      position of the population with respect to the O and t(b) mutant gene frequencies
      was demonstrated. These data were consistent with the idea on the existence of
      the so-called corridor of low frequencies of the first gene and the zone of
      absence of the second gene. One of the highest frequencies of gene d was
      recorded. The frequencies of the other genes were in the ranges observed in other
      populations.

PMID- 22988774
TI  - [Effect of random sample size on the accuracy of nucleotide diversity
      estimation].
AB  - Mathematical simulation has been used to analyze how the sample size affects the
      accuracy of the estimation of molecular variation in a population. The sample
      size was varied from 1/200 to 1/4 of the total size of the simulated population.
      The possible effect of the length of the nucleotide sequences compared has also
      been estimated; it was varied from 500 to 15 000 bp. A tendency towards
      underestimation of the mean nucleotide diversity (pi) by about 25% of the
      expected value has been found. The sample size and/or the length of the
      nucleotide sequence used have been shown to affect more the scatter of the pi
      values than the accuracy of its measurement (the proportion of correct estimates
      of pi is about 14%). The assumption is made that the sample size affects the
      probability of accepting a false null hypothesis in analysis of the demographic
      history of a species.

PMID- 22988776
TI  - Polymorphisms associated with sickle cell disease in Southern Iran.
AB  - Sickle cell disease (SCD) is an inherited autosomal recessive disorder. We aimed
      to describe the spectrum of haplotyes of BS-gene and to investigate a
      relationship with disease phenotype in patients with SCD in Southern Iran. We
      didn't find any significant association between BS-globin gene haplotypes and
      clinical severity of the disease in an Iranian population. The exact mechanism by
      which the BS-globin gene polymorphism affects clinical presentation is not
      obvious; however, further detailed studies at the molecular level, with a larger
      sample size are required to show the mechanisms that influence the clinical
      presentation of SCD in Iranian population.

PMID- 22988777
TI  - [Mapping of the 3' end for artificial human microRNA].
AB  - The 3' end was exactly mapped for has-mir-30a-like artificial human microRNAs
      that specifically recognize the mRNA of the aml1/eto fusion oncogene. The results
      indicated that the intracellular microRNA pool was heterogeneous in linear size
      relative to the 3' end, which is necessary to consider in designing and using
      artificial microRNAs specific for mRNAs of other genes.

PMID- 22988778
TI  - [Identity of the Rht-11 and Rht-B1e reduced plant height genes].
AB  - The Rht (reduced plant height) genes provided a basis for the "green revolution",
      which led to a substantial increase in wheat productivity. More than 20 Rht genes
      are now known in wheat, Rht-B1 and Rht-11 being among the most important ones.
      Analysis of a segregating F2 population and molecular analysis of the common
      wheat cultivars carrying the Rht-11 gene showed that the Rht-11 and Rht-B1e genes
      are identical.

PMID- 22988779
TI  - [Association of polymorphisms in glutathione-S-transferase and DNA repair genes
      with ovarian cancer risk in the Russian population].
AB  - Polymorphism ofglutathione-S-transferase (GSTA1, GSTM1, GSTM3, GSTP1, and GSTT1)
      and DNA repair (ERCC1, ERCC2, and XRCC1) genes in samples of ovarian cancer
      patients and healthy women of the Russian ethnic group was studied. A trend in
      the allele frequency variation of ERCC2 gene single nucleotide polymorphism
      (rs13181, A > C) was revealed. The A allele frequency was higher in the sample of
      patients (60,6% versus 52,9%, P = 0.058).

PMID- 22988780
TI  - Development and psychometric assessment of the undergraduate nursing student
      academic satisfaction scale (UNSASS).
AB  - BACKGROUND AND PURPOSE: To examine the psychometric properties of a newly
      developed instrument: The Undergraduate Nursing Student Academic Satisfaction
      Scale (UNSASS). METHODS: A self-report test-retest questionnaire was administered
      to a convenience sample of 313 students enrolled in Bachelor of Science in
      Nursing (BScN) program in Ontario, Canada. RESULTS: The psychometric analysis
      yielded a 48-item multidimensional instrument. Validity testing revealed a
      content validity index (CVI) of .83. Factor analysis suggested a four-dimension
      scale with distinct factor loadings that all exceeded .4 and explained 50% of the
      variance. The scale had an overall Cronbach's alpha coefficient of .96 and a test
      retest correlation coefficient of .88, indicating a highly reliable instrument.
      CONCLUSIONS: The newly developed instrument provides a tool to comprehensively
      measure the satisfaction of nursing students with the academic aspects of their
      nursing programs.

PMID- 22988781
TI  - Measuring motivation and volition of nursing students in nontraditional learning
      environments.
AB  - The purpose of this study was to identify the best fitting model to represent
      interrelationships between motivation, volition, and academic success for adult
      nursing students learning in nontraditional environments. Participants (N=297)
      completed a survey that incorporated two measures: the Motivated Strategies for
      Learning Questionnaire (MSLQ) and the academic volitional strategies inventory
      (AVSI) as well as demographic information. Exploratory factor analysis (EFA),
      confirmatory factor analysis (CFA), and structural equation modeling (SEM) were
      used for data analysis. In phase 1, EFA resulted in factors that generally
      aligned with previous theoretical factors as defined by the psychometrics used.
      In Phase 2 of the analysis, CFA validated the use of predefined factor
      structures. In Phase 3, SEM analysis revealed that motivation has a larger effect
      on grade point average (GPA; beta = .28, p < .01) than volition (beta = .15, p <
      .05). The covariance between motivation and volition (r = .42, p < .01) was also
      found to be significant. These results suggest that there is a significant
      relationship among motivation, volition, and academic success for adult learners
      studying in nontraditional learning environments. These findings are consistent
      with and elaborate the relationship between motivation and volition with a
      population and setting underrepresented in the research.

PMID- 22988782
TI  - Development and testing of the Jakubik mentoring benefits questionnaire among
      pediatric nurses.
AB  - BACKGROUND AND PURPOSE: The ability to measure the benefits of mentoring among
      bedside nurses is essential for leaders in health care organizations to evaluate
      the effectiveness of mentoring initiatives for nurses. This article describes the
      development and testing of the Jakubik mentoring benefits questionnaire (Jakubik
      MBQ). The instrument is a 36-item tool that uses a 5-point Likert scale to
      measure the individual and organizational benefits of mentoring from the nurse
      protege's perspective. METHODS: The original Jakubik MBQ was a 57-item tool
      developed and validated (validity = .96) with a panel of 6 expert judges prior to
      reliability testing in a pilot study with 11 subjects (Cronbach's alpha = .98).
      Subsequently, the 57-item instrument was used in 3 separate research studies
      (Jakubik, 2007a, 2007b; Jakubik, Eliades, Gavriloff, & Weese, 2011) with strong
      internal consistency reliability evidenced by Cronbach's alpha coefficients of
      .98, .98, and .97, respectively. Exploratory factor analysis was conducted on the
      57-item instrument with the 453 subjects from the aforementioned 3 studies.
      RESULTS: Results of the factor analysis confirmed a total of 6 factors
      (subscales). Based on the factor analysis, the 4 original theoretical subscales
      were confirmed, 2 additional subscales were added, the original subscales were
      renamed, and the instrument was shortened to 36 items with each subscale
      containing 6 items and an overall Cronbach's alpha of .97. CONCLUSIONS: Based on
      these overall findings, the Jakubik MBQ provides a valid and reliable instrument
      for use in measuring the mentoring benefits among pediatric staff nurse proteges
      engaged in mentoring relationships.

PMID- 22988783
TI  - Development of the Thai breast cancer belief scale for Thai immigrants in the
      United States.
AB  - Asian American women have not benefited from the decline in breast cancer
      mortality and have lower rates of mammography use. Understanding mammography
      behaviors among these Asian American women requires culturally specific measures.
      Champion's belief scale was translated into Thai and cultural items were added.
      The Thai breast cancer belief scale (TBCBS), the Suinn-Lew self-identification
      acculturation, and the Asian values scale-revised were administered to 250 Thai
      immigrants. The TBCBS was tested for face validity, construct validity, and
      internal consistency. Factor analysis reflected the 4 constructs of the health
      belief model and accounted for 45.8% of the variance. Cronbach's alpha ranged
      from .77 to .90. Modest correlations were observed between TBCBS subscales and
      acculturation scales. Results indicate that the TBCBS measures breast cancer
      beliefs among Thai immigrant population.

PMID- 22988784
TI  - Multisite recruitment and data collection among older adults: exploring methods
      to conserve human and financial resources.
AB  - The purpose of this article is to describe strategies that were effective in
      recruitment and data collection among older adults in 3 quantitative studies
      while decreasing costs in terms of time and money. Factors effective in reducing
      use of investigators' time and expenses included limiting exclusion of data
      because of abnormal Mini-Cog scores by careful initial screening and avoiding
      repeated reminders or follow-up, collecting data in small groups, collapsing
      consent, dementia screening, and data collection into single sessions, as well as
      accommodating for sensory and literacy deficits. The cross-sectional, descriptive
      studies were conducted among community-dwelling older adults attending senior
      citizen centers and among older adults in independent or assisted living
      apartments within continuing care retirement communities (CCRCs). In the latest
      study, a convenience sample (N=152) was recruited and data collection was
      completed in 4 weeks at a total cost of less than $5,000. Methods common to
      qualitative research and those commonly used in community-based research were
      adapted to reduce time and costs for recruitment, screening, and data collection.
      Given limited availability of research funding, other nursing researchers may
      find one or more of these methods useful.

PMID- 22988785
TI  - World oral health.

PMID- 22988786
TI  - Substantiation of an artificial saliva formulated for use in a masticatory
      apparatus.
AB  - The aim of this work was to substantiate artificial saliva prepared for use in a
      masticator apparatus. Mastication's goal is to produce a viscous and plastic food
      bolus where these properties authorize a safe swallow. Apart from its biochemical
      contribution, saliva is mainly used in this kind of apparatus to provide a
      viscous component to the bolus. Artificial saliva was prepared with water and
      minerals, and completed with mucin and amylase. Different physico-chemical
      conditions were applied and the resultant viscosity was compared to that of human
      saliva. Mechanically- or chemically-stimulated salivas of ten healthy subjects
      were collected. Viscosity was measured with a capillary viscometer in response to
      changes in measurement's temperature, air exposure or pH. The effects of
      circadian saliva collection and the stimulation type on viscosity of human saliva
      were also studied. Viscosity of artificial and human salivas was comparable. An
      increase in the measurement's temperature or a 30 min-exposure of saliva to air
      led to a significant decrease in viscosity of both types of saliva. Amylase in
      artificial saliva did not change viscosity. The viscosity of human saliva
      displayed important subject variability as well as a dependence on the
      stimulation type of saliva production. This work allowed a useful evaluation of
      the formulated artificial saliva. It exhibited similar viscosity as the natural
      saliva in response to different methodological conditions. Therefore the proposed
      artificial saliva satisfies the major requirement of viscosity for a use in the
      masticator apparatus designed to prepare a food bolus.

PMID- 22988787
TI  - [Determination of fluoride in toothpastes marketed in Morocco using a fluoride
      selective electrode].
AB  - INTRODUCTION: Dental caries represents a problem of public health in Morocco and
      the reduction of this pathology is a priority of the Ministry of Health. The use
      of fluoride toothpastes is, at present, recognized as being an effective means
      for the prevention of dental caries. MATERIAL AND METHODS: [corrected] The aim of
      our study was to verify the correspondence of the information marked on
      packagings with the international standards, but also to determine using
      potentiometry the quantity of fluorine presents in toothpastes marketed in
      Morocco from three origins: pharmacies, hypermarkets and ambulant sellers.
      RESULTS: The study concerned 56 toothpastes, 73.2% of toothpastes respect the
      standards of the concerning WHO dates of manufacturing and lapsing. The type of
      fluoride was specified only on 67.8% of packagings and the used concentration of
      fluoride was indicated only in 62.5% of the tested samples. For 56 studied
      toothpastes, the results revealed that if we take into account standards
      recommended by the WHO and the European Union, only 57.1% of toothpastes could
      have an effect dental caries. CONCLUSION: The results of this study show that
      there is a real need of quality control of fluoride toothpastes sold in Morocco
      especially those of the itinerant market.

PMID- 22988788
TI  - Relationship between dental impacts on daily living, satisfaction with the
      dentition and personality profiles among a Palestinian population.
AB  - INTRODUCTION: The aim of this study was to investigate the relationship between
      dental impacts on patients' daily living, satisfaction with the dentition and
      personality profiles. MATERIALS AND METHODS: Fifty-two patients (22 males and 30
      females; mean age 22.7 +/- 5.5 years) were recruited for this study. A "dental
      impact on daily living" (DIDL) questionnaire was used to assess patients'
      satisfaction with their dentition and impacts on daily living. The NEO five
      factor inventory (NEO-FFI) was used to assess personality profiles. RESULTS: The
      dentition had measurable impacts on daily living as well as satisfaction with
      appearance, pain levels, oral comfort, general performance, and eating capability
      (p < 0.001). Older patients were more totally satisfied (p = 0.014), more
      satisfied with appearance (p = 0.034), and less satisfied with general
      performance (p = 0.024). Older patients had higher Conscientiousness scores (p =
      0.001) and lower Openness scores (0.018). Females were more satisfied with eating
      (p < 0.001). Significant correlations were established between neuroticism and
      total DIDL scores (p = 0.006). Extraversion had significant correlations with
      total satisfaction (p < 0.001) as well as satisfaction with appearance (p =
      0.047) and oral comfort (p = 0.008). Significant correlations were also
      established between openness and satisfaction with general performance (p <
      0.001), between Agreeableness and satisfaction with eating (p = 0.001), and
      between Conscientiousness and total satisfaction (p = 0.001), satisfaction with
      pain (p = 0.004), and satisfaction with oral comfort (p = 0.043). CONCLUSIONS:
      The status of the oral cavity might impact on patients' daily living and
      satisfaction with the dentition. Patients' satisfaction with their dentition has
      definitive impacts on daily living and dental perceptions. Personality profiles
      (neuroticism; extraversion; openness; agreeableness and conscientiousness) may
      influence dental perceptions; play a significant role in shaping satisfaction
      with dentition, and help with prediction of dental impacts on daily living.
      Patient satisfaction and psychological profiles should be considered when
      formulating a treatment plan in order to achieve patient acceptance of the
      offered treatment.

PMID- 22988789
TI  - [Orthodontic treatment and gingival hyperplasia: a case report].
AB  - Gingival hyperplasia is a relatively frequent pathologic condition during
      orthodontic treatment. Oral hygiene can be easily altered in such cases because
      of additive and irritative effects of orthodontics appliances. So, adequate
      control of the gingival inflammation is required. The present case reports on a
      13-year-old boy who developed, during orthodontic treatment, a gingival
      hypertrophy that was successfully treated with periodontal surgery consisting on
      an apically positioned flap procedure. For this purpose, multidisciplinary
      approach involving orthodontist and periodontist was crucial in the perspective
      of optimal clinical issues.

PMID- 22988790
TI  - Guided bone regeneration using resorbable and non-resorbable membranes: a
      histological study in dogs.
AB  - AIM: The aim of this study was to evaluate the effectiveness of e-PTFE titanium
      reinforced and Guidor membranes in the management of alveolar ridge deformities.
      MATERIALS AND METHODS: Five beagle dogs were included in the study. Three through
      and through defects of the same size (12 x 5 x 5) were created in each animal,
      one on the right side and two defects 3-4 mm distant from each other on the left
      side. Guidor membrane was applied to the right defect, e-PTFE was applied to one
      of the left defects while the third defect served as control. Three, six and nine
      months following membrane placement, the dogs were euthanized and membranes with
      surrounding bone tissues harvested for histological analysis. RESULTS: Healing in
      each animal was uneventful with no clinical sign of inflammation. Histological
      evaluation indicated the defects covered with both membranes had significantly
      gained greater bone formation than the control defects. On the other hand, the
      control defects healed thin rim of bone mostly with a persistent central defect
      and suprabony connective tissue invasion. CONCLUSIONS: There were no significant
      differences in the bone volume surrounding the membranes in the two experimental
      groups. Control defects produced significantly less amount of bone when compared
      the membrane sites.

PMID- 22988792
TI  - [The detection of myeloperoxidase in case of surgical treatment of ischemic heart
      disease].
AB  - The article deals with the assessment of significance of detection of
      myeloperoxidase in neutrophils to laboratory monitoring of patients conditions
      under surgical treatment of ischemic heart disease. The analysis of clinical
      laboratory data of 123 patients with chronic ischemic heart disease and
      stenocardia of functional class II-III was carried out. The activity of
      myeloperoxidase was detected using the Graham-Knoll cytochemical technique. The
      decrease of activity of myeloperoxidase of neutrophils under ischemic heart
      disease was established. The stereotype neutrophils reaction were lacking in
      patients with cardiac complications after coronary artery bypass grafting.

PMID- 22988791
TI  - [The individual fatty acids in blood plasma, erythrocytes and lipoproteins. The
      comparison of tests results of patients with ischemic heart disease and
      volunteers].
AB  - According to the generally accepted theory, the atherosclerosis is a kind of
      disorder of metabolism of lipids which chemically are the ethers of fatty lipids
      with spirits. Hence, the atherosclerosis is fatty acids pathology. In conformity
      with the biologic classification, among fatty acids it is functionally valid to
      distinguish saturated fatty acids without double bonds; monoenic fatty acids with
      one double bond; unsaturated fatty acids with two or three double bonds and
      polyenic fatty acids with four of six double bonds in chain. The saturated and
      monenic fatty acids are the substrates for cells to groundwork energy, ATP The
      unsaturated fatty acids in vivo are needed to form membranes. The polyenic fatty
      acids are essential since they are precursors of cell synthesis of humoral
      regulators--eicosanoids (prostanoids and leukotrienes). To clarify the
      pathogenesis of the "metabolic pandemics" most prevalent in human population, the
      quantitative determination of individual fatty acids in blood plasma and
      erythrocytes using gas chromatography technique is needed. It is necessary to
      evaluate the content of medium chain fatty acids; palmitic and stearic saturated
      fatty acids; oleic monoenic fatty acid and its transforms--linoleic, linolenic
      and dihomo-gamma-linolenic unsaturated fatty acids; essential polyenic omega-6
      arachidonic, omega-3 eicosapentaenoic and docosahexaenoic fatty acids. The higher
      is in food the content of palmitic saturated fatty acid, palmitoleic and trans
      vaccenic monoenic fatty acids, the more is in patient diet of beef meat and
      products of fat cow's milk. The higher is ratio of palmitic/oleic fatty acids the
      lower is the risk of formation of atheromatosis of arteries intima and
      development of ischemic heart disease and vice versa. The decrease of ratio of
      omega-3/omega-6 essential polyenic fatty acids is undesirable in prognostic
      sense. The metabolism of these acids differs and functional activity of omega-3
      eicosanoid type 3 is higher In case of deficiency of omega-3 and omega-6 polyenic
      fatty acids in cells eicosanoids are synthesized from unsaturated dihomogamma
      linolenic fatty acid and their influence turns out to be aphysiologic. This
      condition is a pathogenic foundation of atherosclerosis. There is a diagnostic
      reason to detect fatty acids in case of diabetes mellitus, obesity, metabolic
      syndrome and partially arterial hypertension.

PMID- 22988793
TI  - [The metabolic changes in blood of women of reproductive age under hypertension
      disease].
AB  - The study established that the initial stages of formation of hypertension
      disease in women of reproductive age is characterized by concomitant imbalance of
      functioning of enzymatic antioxidants. This process results in the
      intensification of free radical oxidation. These changes contribute into
      oxidative modification of protein and lipid components of circulating
      lipoproteins, activation of enzymatic degradation of connective tissue and
      formation of endothelial dysfunction and antipathies.

PMID- 22988794
TI  - [The prognostic value of content of acute phase proteins in development of
      puerperal endometritis].
AB  - The analysis was made of the content of proteins in inflammation acute phase in
      100 healthy puerperants and 157 women with endometritis after cesarean section.
      The established disproportion in protein concentration during acute phase in
      healthy puerperants is considered as a female organism adaptive reaction to
      pregnancy and delivery. As for patients with endometritis, this condition
      testifies the compensatory resources stress, development of pathophysiological
      reactions of organism and intensity of local damages. The concentration of C
      reactive protein and prealbumin in patients with endometritis provides an
      opportunity to forecast the degree of severity of course of disease.

PMID- 22988795
TI  - [The content of Clara's cells protein in highly premature newborns with
      respiration disorders].
AB  - The study was carried out to analyze the content of Clara's cells protein in
      highly premature newborns with respiration disorders in neonatal period. The
      sample of 106 premature newborns of gestational age 26-32 weeks and body mass at
      birth 660-1500 g was examined. The concentration of Clara's cells protein in
      bronchoalveolar liquid and blood serum was higher in patients with inborn
      pneumonia as compared with children with respiratory distress syndrome. The low
      content Clara's cells protein in highly premature newborns with pneumonia was
      related with subsequent development of bronchopulmonary dysplasia.

PMID- 22988796
TI  - [The blood biochemical indicators in drug addicted patients with HIV-infection
      and viral hepatitis].
AB  - The article demonstrates that in drug addicted patients joining of viral
      infections (HIV hepatitis) results in increase of content of total and direct
      bilirubin, alanine aminotransferase and aspartate aminotransferase and in
      decrease of content of urea. These processes testify the development of
      organopathologic complications in the form of liver's barrier functions
      impairment.

PMID- 22988797
TI  - [The algorithm of modern laboratory diagnostics of anemic syndrome in oncologic
      patients].
AB  - The algorithm of analysis of blood of oncologic patients with anemic syndrome was
      elaborated using large clinical sampling (n = 284). It is established that 72% of
      oncologic patients developed anemia by kind of chronic diseases anemia. However
      in some patients the anemic syndrome was caused by the iron deficiency The cases
      of B12 deficient, autoimmune hemolytic anemia were registered and inefficient
      erythropoiesis under metastatic lesion of bone marrow and myelodysplasia
      syndromes as well. The high importance of methods of objective evaluation of iron
      resources (level of ferritin and soluble receptors of transferrin),
      erythropoietic activity of bone marrow (reticulocytes and reticulocyte indices)
      and adequate response to anemia degree (level of endogenic erythropoietin). The
      possibility to detect the concentration of hemoglobin in reticulocytes makes it
      possible to monitor the restoration of hemoglobin content on early stages of
      treatment of patient with iron deficiency anemia.

PMID- 22988798
TI  - [The quantitative evaluation of mutation V617F of gene JAK2 under chronic
      myeloproliferative diseases].
AB  - The mutation V617F of gene JAK2 is detected in 95% of patients with genuine
      polycythemia, in 50% of patients with essential thrombocytemia and idiopathic
      myelofibrosis. The mutation V617F can be applied as a molecular marker of
      response to treatment in patients with chronic myeloproliferative diseases
      associated with this mutation. The technique of quantitative evaluation of V617F
      (sensitivity up to 0.01%) using polymerase chain reaction is described. This
      method can be applied to assess the minimal residual disease in patients with
      chronic myeloproliferative diseases.

PMID- 22988799
TI  - [The analysis of relationship between numbers of hemopoietic hematoblasts and
      laboratory indicators of state of hepatobiliary system in children with
      congenital and hereditary diseases of liver].
AB  - The content of CD34/CD45dim-positive cells in peripheral blood of children with
      congenital and hereditary diseases of hepatobiliary system is studied. The
      analysis of relationship between numbers of studied cells and level of C-reactive
      protein, sCD40L, sCD30 and laboratory parameters specific to liver functions is
      applied The number of CD34-positive hemopoietic hematoblasts in children with
      hepatocirrhosis correlated with the level of C-reactive protein, albumin,
      hemoglobin concentration and quantity of blood erythrocytes. No relationship was
      established with the levels of sDC40L and sDC30. The number ofstudied cells in
      children with liver diseases was higher than in healthy adult donors.

PMID- 22988800
TI  - [The application of method of flow cytometry in diagnostics of hereditary
      spherocytosis (eosin-5 maleimid binding test)].
AB  - The technique of binding eosin-5 maleimid fluorescent dye with lysine-430 of
      first extracellular protein bulge of band 3 of erythrocytes' membranes makes it
      possible to detect the defects of cytoskeleton of erythrocytes as a biological
      foundation of pathogenesis of hereditary spherocytosis. The samples of peripheral
      blood from 125 adult persons and 18 children with established absence of
      hematologic disorders were analyzed The samples of peripheral blood from 19
      patients with verified hereditary spherocytosis were analyzed too. The method of
      flow cytometry was applied to register the average intensity of fluorescence of
      eosin-5 maleimid. The decrease of average intensity of fluorescence of eosin-5
      maleimid of erythrocytes of patients with hereditary spherocytosis as compared
      with data from comparison groups was established in all cases.

PMID- 22988801
TI  - [The computer morphometry of synoviocytes: the diagnostic possibilities and
      importance for patients with post-traumatic osteoarthritis].
AB  - The article deals with the data of computer morphometric analysis ofsynovial
      cells in 27 patients 35-53 years old with knee joint posttraumatic osteoarthritis
      stage I-II according Kellgren and Lowrence classification. The proposed technique
      of image computer analysis made it possible to apply a large specter of cardio
      metric studies of pathologic processes in synovia of patients with post-traumatic
      osteoarthritis. The study results favored the implementation in computer
      morphometry new indicators characterizing brightness and optical density of image
      and permitting to evaluate the degree of compactization and amount of DNA in
      cells nuclei. The synoviocytes were differentiated on types I, II and III on
      basis of form parameters and histograms of distribution of cells nuclei
      brightness. The results of computer analysis of kinetics of proliferation of
      these cells dyed by Feulgen testified that in synovia of patients with post
      traumatic osteoarthritis synoviocytes type II were in G1 -period of interphase
      and synoviocytes type III were in S-period or G2 -period of interphase.

PMID- 22988802
TI  - [The diagnostic value of laboratory markers of epithelium damage in patients
      passing the program hemodialysis].
AB  - The sampling of 82 patients was included into the study to assess the diagnostic
      value of laboratory markers of endothelium dysfunction (homocysteine
      concentration, von Willebrand factor activity) in patients passing the treatment
      of program hemodialysis. The study detected the reliable increase of homocysteine
      level and activity of von Willebrand factor in patients passing hemodialysis. The
      association of increasing of concentration of homocysteine and von Willebrand
      factor activity with rate of cardiovascular complications in patients passing the
      program in patients passing hemodialysis was established.

PMID- 22988803
TI  - [The application of synthetic peptides to characterize the site-directed
      antiviral humoral immune response in patients with respiratory syncytial viral
      infection].
AB  - The article deals with the study of characteristics of epitope-specific humoral
      immune response to respiratory syncytial viral infection depending on nature of
      disease and patients' age. The couple serums from 226 children and adults with
      respiratory syncytial viral infection were analyzed. To detect in enzyme
      immunoassay the epitope-specific IgG the synthetic peptides were applied
      imitating the structure of functionally depended epitopes of F-protein of
      respiratory syncytial virus with amino acid sequences 221-232 (F = SP12), 479-491
      (F-SP13) and G-protein with amino acid sequences 152-164 (G-H13), 184-198 (G
      T15). The respiratory syncytial viral infection neutralizing antibodies were
      detected using the microneutralization reaction. The rate of seroconversions of
      epitope-specific IgG consisted 21-25% in children 3-18 years old under primary
      respiratory syncytial viral infection and increased up to 42-50% in children 3-18
      years old and adults under recurrent episodes of diseases. In these groups, the
      seroconversions of respiratory syncytial virus neutralizing antibodies were
      observed in 42%, 65% and 58% of cases correspondingly. Independently of age of
      patients with diagnosed respiratory syncytial viral infection, the absence of
      conversions of neutralizing antibodies was statistically significant associated
      with the absence of response from epitope-specific IgG. The presence among B-cell
      epitopes of immune dominance of surface glycoproteins of respiratory syncytial
      virus in patients with recurrent (but not primary) respiratory syncytial viral
      infection is detected The hierarchy of epitope-specific immune response in case
      of complicated course of disease (response activity to epitopes: SP12 = G-T15 > G
      H13) differed from the case of uncomplicated course of disease.

PMID- 22988804
TI  - [The characteristics of cell and humoral immunity in patients with acute
      pancreatitis under impact of cold laser radiation].
AB  - The analysis of immune status of 57 patients with acute pancreatitis made it
      possible to assess the impact of cold laser radiation on cell and humoral
      immunity under different forms of acute destructive pancreatitis. The sessions of
      laser therapy applied to patients with acute edematous pancreatitis favored the
      normalization of leucocytes indices, regeneration of lymphocytes. The leucocyte-T
      lymphocyte index came to normality which is an indicator of adequacy of immune
      response.

PMID- 22988805
TI  - [The DS-DIF-KORINE kit to identify microorganisms corynebacterium, including C.
      diphtheriae].
AB  - The DS-DIF-KORINE kit make it possible to identify 20 types of corynebacteriae
      entered the Bergi identification guide (1997) including biovars gravis and mitis
      and belfanti version of diphtheria agent. The possibility to determine its
      toxigenic characteristics is also provided The test system is ready to be applied
      since it has all needed components to implement bacteriologic analysis in search
      of diphtheroids and diagnostics of diphtheria. The presented data demonstrate
      high diagnostic effectiveness of the new DS-DIF-KORINE kit which has the state
      registration in Roszdravnadzor and is adapted for spectrophotometer automatic
      pickup and included into Microbe-Automate and Microbe-2 programs.

PMID- 22988806
TI  - [The architectonics of microbe ecology in the purulent surgery department of
      municipal clinical hospital].
AB  - S. aureus, S. pyogenes, P. aerugenosa, E. coli, P mirabilis, A. baumannii, S.
      epidermidis, K. pneumoniae, E. faecalis, E. cloacae are the priority pathogens of
      various forms of pyoinflammatory diseases. They form the architectonics of
      microbe ecology of the purulent surgery department of multi-type hospital of
      regional level with S.aureus subsp.aureus playing dominating role. In case of
      unchanged specter of priority pathogens of pyoinflammatory and pyoseptic diseases
      the number of gram-positive coccuses decreases at the expense of decrease of
      number of streptococcuses and staphylococcuses. At the same time, the number of
      enterobacteria and gram-negative non-fermentative bacteria increases. The
      resistance ofgram-positive coccuses increases regarding erythromycin, clyndamicin
      and cyprofloxacin. The resistance of gram-negative bacilli increases regarding
      ciprofloxacin, cephalosporins of III-IV generations, amikacin. The resistance is
      the highest among clinical isolates MRSA, K. pneumoniae, A. baumannii. The
      vancomycin is active regarding all gram-positive pathogens. The carbapenems are
      active regarding all enterobacteriae. The carbapenems, cefoperazone/tazobactam,
      cefepime are most active regarding non-fermentative glucose oxidizing bacteria.
      The netimicin is active regarding A.baumannii. The polymyxine is active regarding
      P. aerugenosa. The circulation of S. aureus hospital strain of particular
      genotype is established confirming the propagation of epidemic S. aureus strains
      in Moscow multi-type medical institutions. The strains are genetically affined to
      epidemic strains in European and other countries according the international data
      base (http://SpaServer.ridom.de). The genetic typing of S. aureus ssp. aureus out
      hospital hemocultures detected their considerable genetic variety. The epidemic
      relationship between isolates from different patients is not established. The
      algorithms of rationale antibacterial chemotherapy of pyoinflammatory and
      pyoseptic diseases are developed to be implemented in the purulent surgery
      department of municipal clinical hospital of Moscow.

PMID- 22988808
TI  - [The issues and basic principles of training of physicians of clinical laboratory
      diagnostics].
AB  - The article considers the main positions concerning the clinical laboratory
      diagnostics as an independent clinical specialty and the principles of
      professional training and improvement of specialists. The basic issues
      complicating the training and improvement of personnel to be kept in line with
      actual needs of laboratory service of public health system are discussed. Among
      them are the availability of laboratory academic sub disciplines demanding a
      profound special theoretical education and technical skills; the need to account
      in the process of professional training the variety of forms, sizes and types of
      laboratory structures in different medical institutions; the need of special
      training programs for numerous specialists with non-medical basic education. The
      combination of the present system of postgraduate training of specialists on
      chairs of state educational organizations with initiative involvement of
      specialists in various public forms of permanent professional improvement
      (professional scientific societies meetings, research conferences, internet
      seminars, etc.) is supported Along with a positive appraisal of the existing
      system of training in the state educational institutions and corresponding
      regulation documents, a critique is expressed regarding certain actual documents
      which improperly limit the administrative functions of physicians of clinical
      laboratory diagnostics and complicate training of bacteriologists for clinical
      laboratories.

PMID- 22988807
TI  - [The mechanism of formation of hospital strains of hospital-acquired infections
      agents and modes of prevention].
AB  - The article deals with the mechanisms of formation of hospital strains through
      immunocompromized organism analyzed using the clinically significant signs. It is
      established that application of galavitum with lidocaine results in the
      saprophitization of agents in organism hence preventing the formation of strains
      with "hospital" signs.

PMID- 22988809
TI  - Luminescent microporous metal-organic framework with functional lewis basic sites
      on the pore surface: specific sensing and removal of metal ions.
AB  - A three-dimensional luminescent metal-organic framework, {Mg(DHT)(DMF)(2)}(n)
      (1), based on an excited-state intramolecular proton-transfer (ESIPT) responsive
      linker, 2,5-dihydroxyterephthalic acid (H(2)DHT), has been synthesized, and its
      desolvated microporous framework with pendent -OH groups on the pore surface was
      exploited for the binding and specific sensing of metal ions via Lewis acid-base
      interactions. The luminescence intensity significantly quenches with Cu(II) among
      various s- and d-block metal ions, and highly selective sensing of Cu(II) ions
      has been realized in both solid and solution states (up to nanomolar
      concentration). The immobilized Cu(II) metal ions can be selectively removed by
      chelating agents like ethylenediaminetetraacetic acid without any structural
      disintegration of the framework, as revealed by the luminescence and gas
      adsorption studies.

PMID- 22988810
TI  - Dimerization of an immunoactivating peptide derived from mycobacterial hsp65
      using N-hydroxysuccinimide based bifunctional reagents is critical for its
      antitumor properties.
AB  - We have shown previously that a short pentapeptide derived from the mycobacterial
      heat shock protein hsp65 can be highly activating for the immune system based on
      its strong reactivity with the early activation antigen of lymphocytes CD69.
      Here, we investigated an optimal form of presentation of this antigen to the
      cells of the immune system. Four different forms of the dimerized heptapeptide
      LELTEGY, and of the control inactive dimerized heptapeptide LELLEGY that both
      contained an extra UV active glycine-tyrosine sequence, were prepared using
      dihydroxysuccinimidyl oxalate (DSO), dihydroxysuccinimidyl tartarate (DST),
      dihydroxysuccinimidyl glutarate (DSG), and dihydroxysuccinimidyl suberate (DSS),
      respectively. Heptapeptides dimerized through DST and DSG linkers had optimal
      activity in CD69 precipitation assay. Moreover, dimerization of active
      heptapeptide resulted in a remarkable increase in its proliferation activity and
      production of cytokines in vitro. Furthermore, while DST and DSG dimerized
      heptapeptides both significantly enhanced the cytotoxicity of natural killer
      cells in vitro, only the DSG dimerized compound was active in suppressing growth
      of melanoma tumors in mice and in enhancing the cytotoxic activity of tumor
      infiltrating lymphocytes ex vivo. Thus, while the dimerization of the
      immunoactive peptide caused a dramatic increase in its immunoactivating
      properties, its in vivo anticancer properties were influenced by the chemical
      nature of linker used for its dimerization.

PMID- 22988811
TI  - Factor structure of the Liebowitz Social Anxiety Scale in community-dwelling
      subjects in Japan.
AB  - This study examined the internal consistency and structural/construct validity of
      the Liebowitz Social Anxiety Scale (LSAS) for community-dwelling subjects in
      Japan. A cross-sectional study that included 929 participants was conducted.
      Structural/construct validity was assessed on confirmatory factor analysis. The
      internal consistency reliability was good for the overall LSAS scale (alpha =
      0.97) and for its original four factors (alpha = 0.92-0.89). The original four
      factor model fit the observed data relatively better than alternative models.
      These findings indicate that the LSAS is a valid and reliable measure of anxiety
      symptoms for this community-dwelling population in Japan.

PMID- 22988812
TI  - Burkholdines from Burkholderia ambifaria: antifungal agents and possible
      virulence factors.
AB  - Burkholdines are cyclic lipopeptides with unusual antifungal potency, making them
      promising leads as a new class of antifungal agents. However, a recent report
      using knockout mutagenesis indicates that these and related compounds, such as
      occidiofungins, xylocandins, and cepacidines, may also be synonymous with the
      long-known hemolytic virulence factors found in diverse Burkholderia isolates.
      Because of their possible roles in causing Burkholderia infections or curing
      fungal infections, it is important to fully define their structures and
      biological activities using pure compounds. Here, we report the structures of
      three further burkholdines, Bk-1119, Bk-1213, and Bk-1215, which were elucidated
      using spectroscopic methods. The absolute configuration of this compound class
      was determined for the first time using a combination of spectroscopy and
      chemical degradation techniques. Antifungal and hemolytic activities were
      assessed for five pure burkholdines, representative of the structural diversity
      of this lipopeptide class. All of the burkholdines were potent antifungal and
      hemolytic agents, validating their probable role in virulence. However, one of
      the burkholdines (Bk-1119) exhibited a >30-fold selectivity for fungi versus
      sheep erythrocytes and was more than 25-fold more potent than amphotericin
      against some fungal strains. Therefore, burkholdines have potential to
      selectively target fungal infections.

PMID- 22988813
TI  - Exploring structural and optical properties of fluorescent proteins by squeezing:
      modeling high-pressure effects on the mStrawberry and mCherry red fluorescent
      proteins.
AB  - Molecular dynamics calculations of pressure effects on mStrawberry and mCherry
      fluorescent proteins are reported. The simulations reveal that mStrawberry has
      much floppier structure at atmospheric pressure, as evidenced by larger backbone
      fluctuations and the coexistence of two conformers that differ by Ser146
      orientation. Consequently, pressure increase has a larger effect on mStrawberry,
      making its structure more rigid and reducing the population of one of the
      conformers. The most significant effect of pressure increase is in the hydrogen
      bonding network between the chromophore and the nearby residues. The quantum
      mechanics/molecular mechanics calculations of excitation energies in mStrawberry
      explain the observed blue shift and identify Lys70 as the residue that has the
      most pronounced effect on the spectra. The results suggest that pressure increase
      causes an initial increase of fluorescence yield only for relatively floppy
      fluorescent proteins, whereas the fluorescent proteins that have more rigid
      structures have quantum yields close to their maximum. The results suggest that a
      low quantum yield in fluorescent proteins is dynamic in nature and depends on the
      range of thermal motions of the chromophore and fluctuations in the H-bonding
      network rather than on their average structure.

PMID- 22988814
TI  - Synthesis of lignin nanofibers with ionic-responsive shells: water-expandable
      lignin-based nanofibrous mats.
AB  - A series of ionic responsive poly(N-isopropylacrylamide) (PNIPAM) surface
      modified lignin nanofiber mats were prepared by aqueous surface-initiated atom
      transfer radical polymerization (SI-ATRP). PNIPAM brushes with various molecular
      weights, thickness, and grafting densities were immobilized on electrospun lignin
      nanofiber mats by adjusting initial monomer concentration and surface initiator
      density. ATR-FTIR, SEM, TGA, XPS, and water contact angle measurements confirmed
      successful surface modification. Analysis of the PNIPAM-modified lignin nanofiber
      mats (Lig-PN) found that the lower critical solution temperature (LCST) was
      similar to that of PNIPAM and demonstrated ionic responsive characteristics. With
      increasing ionic concentration, the water contact angles of the Lig-PN increased
      correspondingly. AFM images showed that the PNIPAM on the lignin nanofiber mat
      surface expanded in water and contracted in 0.5 M Na(2)SO(4).

PMID- 22988815
TI  - Host specificity of North American Rhabdias spp. (Nematoda: Rhabdiasidae):
      combining field data and experimental infections with a molecular phylogeny.
AB  - Lungworms of the cosmopolitan genus Rhabdias are among the most common parasites
      of amphibians and squamate reptiles. The present study used experimental
      infections, field studies, and a molecular phylogeny to determine the host
      specificity of 6 Rhabdias spp. that infect snakes and anurans from North America.
      The molecular phylogeny suggests Rhabdias ranae from Nebraska and Mississippi may
      represent separate, cryptic species. In addition, the phylogeny strongly supports
      separate clades for anuran and snake lungworms. Field studies and experimental
      infections indicate that snake lungworms are generalist snake parasites; however,
      laboratory experiments also suggest that lizards can be infected under some
      environmental conditions. Lungworms from anurans were found not to infect
      salamanders or reptiles, in nature or in the laboratory; anuran lungworm species
      ranged from strict host specificity, e.g., R. ranae from Nebraska, to relative
      generalist, e.g., Rhabdias joaquinensis from Nebraska. Overall, host specificity
      for species of Rhabdias does not provide support for the evolution of progressive
      specialization over time. For most species of lungworms, host specificity in
      nature appears to be limited by both ecological and physiological factors, which
      vary between species and their hosts. Furthermore, some lungworms, e.g., Rhabdias
      bakeri from Missouri, appear to be tracking host resources instead of host
      phylogenies, an example of ecological fitting.

PMID- 22988816
TI  - Cellulose nanocrystal iridescence: a new model.
AB  - A homogeneous aqueous dispersion of cellulose nanocrystals (CNs) that is left to
      evaporate in a Petri dish self-organizes into smectic liquid crystals that are
      actually liquid multilamellar structures. As evaporation proceeds, the liquid
      multilamellar structures solidify to become a solid multilamellar film. Each
      solid lamella is in the submicrometer range, and its iridescence is easily
      explained by classical light interference. A careful inspection of each solid
      lamella revealed long, oriented arrays of colloids. Interestingly, the array
      orientation is generally the same for each superposed layer. This is exceptional
      because the stratification appears first in the liquid, and the solid colloids
      are formed in each stratum at the very end of the process. Our findings are
      supported by optical, atomic force, and electron microscope observations and by
      laser diffraction observations. The multilamellar solid film model is easier to
      engineer than the helical model currently used to explain the iridescence and
      optical activities of CN solid films. This new understanding should promote the
      industrial production of colorful CN coatings and inks as a green alternative for
      decades to come.

PMID- 22988817
TI  - Mapping single molecule sequencing reads using basic local alignment with
      successive refinement (BLASR): application and theory.
AB  - BACKGROUND: Recent methods have been developed to perform high-throughput
      sequencing of DNA by Single Molecule Sequencing (SMS). While Next-Generation
      sequencing methods may produce reads up to several hundred bases long, SMS
      sequencing produces reads up to tens of kilobases long. Existing alignment
      methods are either too inefficient for high-throughput datasets, or not sensitive
      enough to align SMS reads, which have a higher error rate than Next-Generation
      sequencing. RESULTS: We describe the method BLASR (Basic Local Alignment with
      Successive Refinement) for mapping Single Molecule Sequencing (SMS) reads that
      are thousands of bases long, with divergence between the read and genome
      dominated by insertion and deletion error. The method is benchmarked using both
      simulated reads and reads from a bacterial sequencing project. We also present a
      combinatorial model of sequencing error that motivates why our approach is
      effective. CONCLUSIONS: The results indicate that it is possible to map SMS reads
      with high accuracy and speed. Furthermore, the inferences made on the mapability
      of SMS reads using our combinatorial model of sequencing error are in agreement
      with the mapping accuracy demonstrated on simulated reads.

PMID- 22988818
TI  - Friedelin and lanosterol from Garcinia prainiana stimulated glucose uptake and
      adipocytes differentiation in 3T3-L1 adipocytes.
AB  - Friedelin and lanosterol have been isolated from twigs of Garcinia prainiana.
      Their structures were elucidated by spectroscopic methods. The compounds were
      examined for their effects on 3T3-L1 adipocytes. In the MTT assay, it was found
      that the compounds had no cytotoxic effects up to 25 uM. Adipocyte
      differentiation analysis was carried out by Oil Red O staining method. In the
      presence of adipogenic cocktail (MDI), it was found that friedelin and lanosterol
      enhanced intracellular fat accumulation by 2.02 and 2.18-fold, respectively,
      compared with the vehicle-treated cells. Deoxyglucose uptake assay was used to
      examine the insulin sensitivity of adipocytes in the presence of the compounds.
      It was found that friedelin was able to stimulate glucose uptake up to 1.8-fold
      compared with insulin-treated cells. It was suggested that friedelin and
      lanosterol may be beneficial to mimic insulin action that would be useful in the
      treatment of diabetes type 2 patients.

PMID- 22988819
TI  - Orientational time correlation functions for vibrational sum-frequency
      generation. 1. Acetonitrile.
AB  - Orientational time correlation functions (TCFs) are derived for vibrational sum
      frequency generation (VSFG) spectroscopy of the symmetric and asymmetric
      stretches of high-symmetry oscillators such as freely rotating methyl groups,
      acetylenic C-H groups, and cyanide groups. Molecular dynamics simulations are
      used to calculate these TCFs and the corresponding elements of the second-order
      response for acetonitrile at the liquid/vapor and liquid/silica interfaces. We
      find that the influence of reorientation depends significantly on both the
      functional group in question and the polarization conditions used. Additionally,
      under some circumstances, reorientation can cause the VSFG response function to
      grow with time, partially counteracting the effects of other dephasing
      mechanisms. 

PMID- 22988820
TI  - Lamotrigine ameliorates seizures and psychiatric comorbidity in a rat model of
      spontaneous absence epilepsy.
AB  - PURPOSE:   Lamotrigine (LTG) is an effective clinical treatment for epilepsy
      associated with absence seizures. However, the impact of LTG administration in
      studies employing various animal models of epilepsy remains controversial. This
      study aimed to clarify the outcomes of LTG treatment on absence seizures and
      comorbid anxiety and depression disorders in Long-Evans rats with spontaneous
      spike-wave discharges (SWDs). METHODS:   LTG (10 mg/kg) or water vehicle was
      chronically administered perorally to Long-Evans rats (twice daily for 35 days).
      Cortical activities were recorded to assess the presence of SWDs. Five behavioral
      tests, including the open field (OF), elevated plus maze (EPM), sucrose
      consumption (SC), sucrose preference, and forced swimming (FS) tests, were
      performed after LTG/vehicle treatment. The behavioral indexes of these tests were
      designed to assess anxiety (OF and EPM tests), depression (SC and FS tests), and
      preference for hedonistic stimuli (sugar preference test). KEY FINDINGS:   Total
      SWD duration, SWD number, and mean SWD duration were significantly decreased in
      rats that received 35-day LTG treatment compared with rats that received vehicle
      treatment. Rats with spontaneous SWDs versus rats with no SWDs showed significant
      levels of anxiety and depression in the OF, EPM, and SC tests. Rats with SWDs
      also showed longer immobility in the FS test. However, the LTG-treated group
      compared with the vehicle group presented with significantly lower manifestations
      of anxiety and depression in the OF, EPM, SC, and sucrose preference tests and
      shorter immobility in the FS test. SIGNIFICANCE:   The results of this study
      suggest that chronic LTG treatment can benefit patients with epilepsy via
      suppression of absence seizures and amelioration of comorbid anxiety and
      depression.

PMID- 22988821
TI  - Dissecting molecular stress networks: identifying nodes of divergence between
      life-history phenotypes.
AB  - The complex molecular network that underlies physiological stress response is
      comprised of nodes (proteins, metabolites, mRNAs, etc.) whose connections span
      cells, tissues and organs. Variable nodes are points in the network upon which
      natural selection may act. Thus, identifying variable nodes will reveal how this
      molecular stress network may evolve among populations in different habitats and
      how it might impact life-history evolution. Here, we use physiological and
      genetic assays to test whether laboratory-born juveniles from natural populations
      of garter snakes (Thamnophis elegans), which have diverged in their life-history
      phenotypes, vary concomitantly at candidate nodes of the stress response network,
      (i) under unstressed conditions and (ii) in response to an induced stress. We
      found that two common measures of stress (plasma corticosterone and liver gene
      expression of heat shock proteins) increased under stress in both life-history
      phenotypes. In contrast, the phenotypes diverged at four nodes both under
      unstressed conditions and in response to stress: circulating levels of reactive
      oxygen species (superoxide, H(2)O(2)); liver gene expression of GPX1 and
      erythrocyte DNA damage. Additionally, allele frequencies for SOD2 diverge from
      neutral markers, suggesting diversifying selection on SOD2 alleles. This study
      supports the hypothesis that these life-history phenotypes have diverged at the
      molecular level in how they respond to stress, particularly in nodes regulating
      oxidative stress. Furthermore, the differences between the life-history
      phenotypes were more pronounced in females. We discuss the responses to stress in
      the context of the associated life-history phenotype and the evolutionary
      pressures thought to be responsible for divergence between the phenotypes.

PMID- 22988823
TI  - Platelet-rich plasma-derived growth factors promote osteogenic differentiation of
      rat muscle satellite cells: in vitro and in vivo studies.
AB  - PRP (platelet-rich plasma)-derived growth factors are a new application of tissue
      engineering and a developing area for researchers and clinicians. We have
      assessed the effects of PRP-derived growth factors on the proliferation and
      osteogenic differentiation of rMSCs (rat muscle satellite cells), and constructed
      a novel tissue engineering bone composed of PRP-derived growth factors and rMSCs.
      PRP were created by a freeze-thaw process. rMSCs were isolated from rat
      masticatory muscle using serial platings technique. Wst-1 assay, SEM (scanning
      electron microscopy), ALP (alkaline phosphatase) activity, total protein
      concentration, AR (Alizarin red S) staining, calcium analyses and RT-PCR (reverse
      transcription-PCR) of osteogenic-related genes were used to assess the effect of
      PRP-derived growth factors on proliferation and osteogenic differentiation of
      cultured rMSCs on scaffolds. The different composite scaffolds were implanted to
      the subcutaneous spaces of nude mice. H&E (haematoxylin and eosin) and Masson's
      trichrome staining were used to examine the ectopic bone formation. In vitro, we
      found that PRP-derived growth factors showed excellent cell compatibility and
      significantly enhanced cell proliferation over serum and control groups at 48 and
      72 h. SEM, ALP activity, AR staining, calcium analyses and RT-PCR showed that PRP
      derived growth factors significantly increased cells osteogenic differentiation
      when compared with other groups. In vivo examination showed that more fibrous
      tissue capsule and bone with lamellar structures appeared in PRP-derived growth
      factors groups. These results suggest that the PRP-derived growth factors
      significantly promote rMSCs proliferation, osteogenic differentiation compared
      with serum and scaffolds alone, and may be suitable for stem cell growth factors
      delivery and bone tissue engineering.

PMID- 22988822
TI  - Celiac disease arthropathy and autoimmunity study.
AB  - BACKGROUND AND AIM: To evaluate presence of sero-negative spondyloarthritis (SpA)
      in celiac disease (CD) patients, and whether compliance with a gluten free diet
      (GFD) improved arthritis manifestations in these patients. METHODS: We undertook
      a prospective, questionnaire based, cross-sectional cohort study to evaluate the
      presence or absence of SpA simultaneously in both CD and non-CD cohorts. RESULTS:
      356/590 (60.3%) patients with CD participated in this study. 99% had diagnosis
      confirmed by a diagnostic test (79% small bowel biopsy, 19.8% blood test, 3.9%
      stool test). Approximately 131 (37%) cases of arthritis were reported in CD
      patients. Of the 6/356 CD patients with seronegative spondyloarthritides, four
      had sacroiliitis, two ankylosing spondylitis, and one psoriatic arthritis,
      compared to one ankylosing spondylitis and five psoriatic arthritis in non-CD.
      Osteoarthritis (89 vs 59, P = 0.93) was the most common diagnosis reported by
      respondents. More CD patients with diarrhea (94%) and anemia (81%) improved on
      GFD, compared to arthritis symptoms (30%). Autoimmune thyroiditis (10.6% vs
      0.4%), insulin dependent diabetes mellitus (IDDM) (2.2% vs 1.7%), systemic Lupus
      erythematosus (SLE) (1.1% vs 0), and psoriasis (12.9% vs 5.5%) occurred more
      frequently in CD patients. The prevalence of Crohn's disease, ulcerative colitis,
      Sjogren's syndrome, primary biliary cirrhosis, and primary sclerosing cholangitis
      was around 1% each. Univariate Logistic regression analysis showed <= high school
      education (odds ratio [OR] 2.01, P < 0.003), age >= 60 years (OR 4.13, P <
      0.001), and osteoporosis (OR 2.78, P < 0.001) to be significantly associated with
      report of arthritis in CD patients. CONCLUSION: We did not find a high rate of
      SpA in CD patients. In contrast, increased rates of autoimmune thyroiditis, SLE,
      IDDM, and psoriasis were seen in CD.

PMID- 22988824
TI  - Nature of fatigue moderates depressive symptoms and anxiety in sarcoidosis.
AB  - OBJECTIVES: Fatigue, depressive symptoms, and anxiety are frequently reported in
      sarcoidosis. However, the relationship between these debilitating symptoms is
      unclear. Therefore, the purpose of this prospective follow-up study was to
      identify the prevalence of depressive symptoms and anxiety in sarcoidosis
      patients, stratified for the nature of fatigue. In addition, we examined whether
      depressive symptoms and anxiety predicted fatigue. DESIGN: This is a prospective
      follow-up study. METHODS: Sarcoidosis outpatients (n = 274) were included.
      Clinical data were obtained from medical records. At baseline, patients completed
      the Fatigue Assessment Scale (FAS), the Center for Epidemiological Studies
      Depression Scale (CES-D), and the State and Trait Anxiety Inventory (STAI). After
      6, 12, and 18 months patients completed the FAS again. RESULTS: Concomitant
      fatigue (FAS > 21) and high-trait anxiety (STAI > 40) was frequently reported (35
      36%). The combination of fatigue and high levels of depressive symptoms (CES-D >
      16) was reported in 43-46%. Combined high-trait anxiety and high levels of
      depressive symptoms were reported in 31% of the patients. These percentages were
      higher in patients with all day fatigue, compared with patients with
      intermittent, or mild fatigue. Both anxiety and depressive symptoms were
      significant predictors of high fatigue scores. CONCLUSIONS: Nature of fatigue
      moderates the relationships between fatigue and anxiety and fatigue and
      depressive symptoms in sarcoidosis. Hence, beside fatigue, depressive symptoms
      and anxiety should be an integral part of the multidisciplinary management of
      sarcoidosis patients. STATEMENT OF CONTRIBUTION: What is already known on this
      subject? Fatigue is a frequently reported symptom in sarcoidosis. Symptoms such
      as depressive symptoms and anxiety are also prevalent in sarcoidosis. However,
      the relationships between these symptoms are still unclear and require more
      research. What does this study add? This paper shows that fatigue is often
      accompanied by depressive symptoms and anxiety, although these symptoms are not
      fully overlapping. In addition, depressive symptoms and anxiety predict fatigue
      after follow-up. Fatigue, depressive symptoms and anxiety are most strongly
      correlated in patients with All Day Fatigue, which indicate that these patients
      may benefit from psychological interventions in the management of fatigue.

PMID- 22988826
TI  - Treatment of chronic myelomonocytic leukemia with azacitidine.

PMID- 22988827
TI  - Vascular inflammation and aortic stiffness relate to early left ventricular
      diastolic dysfunction in prehypertension.
AB  - Prehypertension is characterized by an increased cardiovascular risk and by an
      increased prevalence of target organ damage compared with the pure normotensive
      state. The present study was designed to assess in prehypertensive subjects the
      possible relationships between early left ventricular dysfunction, vascular
      inflammation and aortic stiffness. The study population consisted of 31 untreated
      prehypertensive subjects (age: 34 +/- 6 years, mean +/- SD) and 31 age-matched
      pure normotensive controls. Left ventricular function was assessed by
      echocardiography, aortic distensibility parameters were derived from aortic
      diameters measured by ultrasonography, and high-sensitivity C-reactive protein
      was assessed by latex-enhanced reagent. Prehypertensive subjects displayed a
      significantly lower E/A ratio and a significantly greater deceleration time and
      isovolumetric relaxation time compared with normotensive controls. They also
      displayed aortic systolic diameter, diastolic diameter and mean aortic stiffness
      index beta significantly increased while systo-diastolic diameter change, mean
      aortic distensibility and aortic strain were significantly reduced compared with
      controls. Values of inflammatory markers were increased. At multiple regression
      analysis, E/A ratio was significantly related to high-sensitivity C-reactive
      protein and aortic stiffness index beta, after correction for age, left
      ventricular mass index and mean blood pressure (beta coefficient = -0.49, overall
      r(2) = 0.24, p = 0.01 and beta coefficient =-0.46, overall r(2) = 0.21, p = 0.02,
      respectively). Thus, in prehypertension, left ventricular dysfunction is
      significantly related to vascular inflammation and aortic stiffness, suggesting
      that early cardiac and vascular alterations may have an increased inflammatory
      process as a common pathophysiological link.

PMID- 22988828
TI  - 17beta-estradiol protects human skin fibroblasts and keratinocytes against
      oxidative damage.
AB  - BACKGROUND: Reactive oxygen species (ROS) cause severe damage to extracellular
      matrix and to molecular structure of DNA, proteins and lipids. Accumulation of
      these molecular changes apparently constitutes the basis of cell ageing. 17b
      estradiol (E2) has a key role in skin ageing homeostasis as evidenced by the
      accelerated decline in skin appearance seen in the perimenopausal years.
      Oestrogens improve many aspects of the skin such as skin thickness,
      vascularization, collagen content and quality. Despite these clinical evidences,
      the effects of oestrogens on skin at the cellular level need further
      clarification. MATERIALS AND METHODS: HaCaT and human fibroblasts were cultured
      under various conditions with E2 and H2 O2 ; then were subjected to
      immunofluorescence and western blot analysis. Lipoperoxidation was investigated
      using BODIPY. RESULTS: In human fibroblasts oxidative stress decreases
      procollagen-I synthesis, while E2 significantly increases it. Fibroblasts and
      HaCaT cells viability in the presence of E2 demonstrates a notably increased
      resistance to H2 O2 effects. Furthermore E2 is able to counteract H2 O2 -mediated
      lipoperoxidation and DNA oxidative damage in skin cells. DISCUSSION: In this
      study we highlight that the menopause-associated oestrogens decline is involved
      in reduced collagen production and that E2 could counteract the detrimental
      effects of oxidative stress on the dermal compartment during skin aging.
      Furthermore, our data show that physiological concentrations of oestrogens are
      able to interfere with ROS-mediated cell viability reduction and to protect human
      skin cells against oxidative damage to cellular membranes and nucleic acids
      structure. CONCLUSION: Our experimental data show that the presence of 17beta
      estradiol may protect skin cells against oxidative damage and that the dramatic
      lowering of oestrogen levels during menopause, could render skin more susceptible
      to oxidative damage.

PMID- 22988825
TI  - Advanced maternal age and risk perception: a qualitative study.
AB  - BACKGROUND: Advanced maternal age (AMA) is associated with several adverse
      pregnancy outcomes, hence these pregnancies are considered to be "high risk." A
      review of the empirical literature suggests that it is not clear how women of AMA
      evaluate their pregnancy risk. This study aimed to address this gap by exploring
      the risk perception of pregnant women of AMA. METHODS: A qualitative descriptive
      study was undertaken to obtain a rich and detailed source of explanatory data
      regarding perceived pregnancy risk of 15 women of AMA. The sample was recruited
      from a variety of settings in Winnipeg, Canada. In-depth interviews were
      conducted with nulliparous women aged 35 years or older, in their third
      trimester, and with singleton pregnancies. Interviews were recorded and
      transcribed verbatim, and content analysis was used to identify themes and
      categories. RESULTS: Four main themes emerged: definition of pregnancy risk,
      factors influencing risk perception, risk alleviation strategies, and risk
      communication with health professionals. CONCLUSIONS: Several factors may
      influence women's perception of pregnancy risk including medical risk,
      psychological elements, characteristics of the risk, stage of pregnancy, and
      health care provider's opinion. Understanding these influential factors may help
      health professionals who care for pregnant women of AMA to gain insight into
      their perspectives on pregnancy risk and improve the effectiveness of risk
      communication strategies with this group.

PMID- 22988829
TI  - Sentinel lymph node mapping and biopsy using radioactive tracer in gastric
      cancer.
AB  - BACKGROUND: Lymph node metastasis is one of the most important prognostic factors
      in gastric cancer survival. Sentinel lymph node (SLN) mapping and biopsy may
      reduce the extension of lymph node dissection by determination of lymph node
      involvement. The current study prospectively evaluates the feasibility and
      reliability of SLN biopsy in gastric cancer. METHODS: A total of 30 patients with
      gastric cancer with a preoperative imaging stage of T1-T2 or T3, N0 and M0 were
      enrolled in the study. Furthermore, 2-16 h prior to each operation, (99m) Tc
      sulphur colloid solution (0.5 mL, 2 mCi/mL) was endoscopically injected into the
      submucosal layer around the primary lesion. Lymph nodes were examined using a
      hand-held gamma probe. Subsequently, a total or subtotal gastrectomy and D2
      lymphadenectomy was performed in each patient. RESULTS: The success rate of SLN
      biopsy was 100%. Sensitivity, specificity, positive predictive value and negative
      predictive value were 91.7%, 100%, 100% and 75%, respectively. Both of the two
      false-negative cases were in the T3 group. In cases of T2 tumours, the
      sensitivity was 100%. DISCUSSION: SLN biopsy using a gamma probe in early stage
      gastric cancer seems to be a safe, feasible and accurate procedure with high
      sensitivity in predicting regional lymph node involvement.

PMID- 22988830
TI  - Differing associations of white matter lesions and lacunar infarction with
      retinal microvascular signs.
AB  - BACKGROUND: White matter lesions (WML) and lacunar infarcts (LI) are believed to
      have microvascular etiologies but the exact microvascular changes occurring in
      each is unclear. AIM: Using the retina as a proxy, we assessed retinal
      microvascular changes in WML and LI. METHODS: We prospectively recruited 1211
      acute stroke patients. Four subgroups were identified from neuroimaging: WML
      alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs
      identified retinopathy and retinal arteriolar wall signs and measured retinal
      vascular caliber. RESULTS: Compared with 448 controls with neither WML nor LI,
      384 patients with only WML were more likely to have retinopathy [odds ratio (OR)
      1.5, 95% confidence interval (CI) 1.1 to 2.1] and enhanced arteriolar light
      reflex (OR 1.6, 95% CI 1.1 to 2.3); 200 patients with only LI were more likely to
      have arteriolar narrowing (OR 1.6, 95% CI 1.1 to 2.3) and enhanced arteriolar
      light reflex (OR 1.6, 95% CI 1.0 to 2.4); and 179 patients with both WML and LI
      were more likely to have arteriovenous nicking (OR 1.7, 95% CI 1.1 to 2.6),
      enhanced arteriolar light reflex (OR 2.0, 95% CI 1.3 to 3.2) and wider venules
      (OR 2.3, 95% CI 1.4 to 3.6). All analyses were adjusted for age, gender, study
      site and cardiovascular risk factors. CONCLUSION: Both WML and LI were associated
      with retinal microvascular signs, supporting a microvascular etiology. Differing
      patterns of association suggest different mechanisms may predominate, e.g.
      greater endothelial permeability in WML, and ischemia associated with arteriolar
      wall disease in LI.

PMID- 22988832
TI  - Capping ligands as selectivity switchers in hydrogenation reactions.
AB  - We systematically investigated the role of surface modification of nanoparticles
      catalyst in alkyne hydrogenation reactions and proposed the general explanation
      of effect of surface ligands on the selectivity and activity of Pt and Co/Pt
      nanoparticles (NPs) using experimental and computational approaches. We show that
      the proper balance between adsorption energetics of alkenes at the surface of NPs
      as compared to that of capping ligands defines the selectivity of the
      nanocatalyst for alkene in alkyne hydrogenation reaction. We report that addition
      of primary alkylamines to Pt and CoPt(3) NPs can drastically increase selectivity
      for alkene from 0 to more than 90% with ~99.9% conversion. Increasing the primary
      alkylamine coverage on the NP surface leads to the decrease in the binding energy
      of octenes and eventual competition between octene and primary alkylamines for
      adsorption sites. At sufficiently high coverage of catalysts with primary
      alkylamine, the alkylamines win, which prevents further hydrogenation of alkenes
      into alkanes. Primary amines with different lengths of carbon chains have similar
      adsorption energies at the surface of catalysts and, consequently, the same
      effect on selectivity. When the adsorption energy of capping ligands at the
      catalytic surface is lower than adsorption energy of alkenes, the ligands do not
      affect the selectivity of hydrogenation of alkyne to alkene. On the other hand,
      capping ligands with adsorption energies at the catalytic surface higher than
      that of alkyne reduce its activity resulting in low conversion of alkynes.

PMID- 22988833
TI  - The clinical course of alcoholic cirrhosis: effects of hepatic metabolic
      capacity, alcohol consumption, and hyponatremia--a historical cohort study.
AB  - BACKGROUND: The cirrhosis complications hepatic encephalopathy, ascites, and
      variceal bleeding increase mortality but develop in random sequence. Therefore
      prognoses based on the presence or absence of these clinical complications are
      inherently inaccurate, and other determinants of the clinical course should be
      identified. Here we present our study of patho-etiological factors that may be
      causally involved in the development of specific complications to alcoholic
      cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing
      hepatic metabolic capacity, continued alcohol consumption, and circulatory
      dysfunction. METHODS: We followed a Danish community-based cohort of 466 patients
      with alcoholic cirrhosis. Stratified Cox regression was used to examine the
      effects of GEC (a measure of hepatic metabolic capacity), alcohol consumption,
      and plasma sodium concentration (a measure of circulatory dysfunction) on the
      hazard rates of first-time hepatic encephalopathy, first-time ascites, first-time
      variceal bleeding, and mortality. We adjusted for confounding by comorbidity,
      gender, and age. Data on risk factors and confounders were updated during follow
      up. RESULTS: A low GEC increased the risk of first-time hepatic encephalopathy
      (hazard ratio [HR] 1.21 per 0.1 mmol/min GEC loss, 95% CI 1.11-1.31), but was
      unassociated with other adverse events. Alcohol consumption increased the risk of
      first-time ascites (HR 3.18, 95% CI 1.19-8.47), first-time variceal bleeding (HR
      2.78, 95% CI 1.59-4.87), and mortality (HR 2.45, 95% CI 1.63-3.66), but not the
      risk of first-time hepatic encephalopathy. Hyponatremia increased the risk of all
      adverse events. CONCLUSIONS: Reduced hepatic metabolic capacity, alcohol
      consumption, and hyponatremia were causally involved in the development of
      specific complications to alcoholic cirrhosis.

PMID- 22988834
TI  - Social support for women of reproductive age and its predictors: a population
      based study.
AB  - BACKGROUND: Social support is an exchange of resources between at least two
      individuals perceived by the provider or recipient to be intended to promote the
      health of the recipient. Social support is a major determinant of health. The
      objective of this study was to determine the perceived social support and its
      associated sociodemographic factors among women of reproductive age. METHODS:
      This was a population-based cross-sectional study with multistage random cluster
      sampling of 1359 women of reproductive age. Data were collected using
      questionnaires on sociodemographic factors and perceived social support (PRQ85
      Part 2). The relationship between the dependent variable (perceived social
      support) and the independent variables (sociodemographic characteristics) was
      analyzed using the multivariable linear regression model. RESULTS: The mean score
      of social support was 134.3 +/- 17.9. Women scored highest in the "worth"
      dimension and lowest in the "social integration" dimension. Multivariable linear
      regression analysis indicated that the variables of education, spouse's
      occupation, Sufficiency of income for expenses and primary support source were
      significantly related to the perceived social support. CONCLUSION:
      Sociodemographic factors affect social support and could be considered in
      planning interventions to improve social support for Iranian women.

PMID- 22988835
TI  - Behavioral and physiological female responses to male sex ratio bias in a pond
      breeding amphibian.
AB  - INTRODUCTION: The phenomenon of sexual conflict has been well documented, and in
      populations with biased operational sex ratios the consequences for the rarer sex
      can be severe. Females are typically a limited resource and males often evolve
      aggressive mating behaviors, which can improve individual fitness for the male
      while negatively impacting female condition and fitness. In response, females can
      adjust their behavior to minimize exposure to aggressive mating tactics or
      minimize the costs of mating harassment. While male-male competition is common in
      amphibian mating systems, little is known about the consequences or responses of
      females. The red-spotted newt (Notophthalmus viridescens) is a common pond
      breeding amphibian with a complex, well-studied mating system where males
      aggressively court females. Breeding populations across much of its range have
      male-biased sex ratios and we predicted that female newts would have behavioral
      mechanisms to mitigate mating pressure from males. We conducted four experiments
      examining the costs and behavioral responses of female N. viridescens exposed to
      a male-biased environment. RESULTS: In field enclosures, we found that female
      newts exposed to a male-biased environment during the five-month breeding season
      ended with lower body condition compared to those in a female-biased environment.
      Shorter-term exposure to a male-biased environment for five weeks caused a
      decrease in circulating total leukocyte and lymphocyte abundance in blood, which
      suggests females experienced physiological stress. In behavioral experiments, we
      found that females were more agitated in the presence of male chemical cues and
      females in a male-biased environment spent more time in refuge than those in a
      female-biased environment. CONCLUSIONS: Our results indicate that male-biased
      conditions can incur costs to females of decreased condition and potentially
      increased risk of infection. However, we found that females can also alter their
      behavior and microhabitat use under a male-biased sex ratio. Consistent with
      surveys showing reduced detection probabilities for females, our research
      suggests that females avoid male encounters using edge and substrate habitat. Our
      work illustrates the integrated suite of impacts that sexual conflict can have on
      the structure and ecology of a population.

PMID- 22988836
TI  - BMP4 can generate primordial germ cells from bone-marrow-derived pluripotent stem
      cells.
AB  - Evidence of germ cell derivation from embryonic and somatic stem cells provides
      an in vitro model for the study of germ cell development, associated epigenetic
      modification and mammalian gametogenesis. More importantly, in vitro derived
      gametes also represent a potential strategy for treating infertility. In mammals,
      male and female gametes, oocyte and sperm, are derived from a specific cell
      population, PGCs (primordial germ cells) that segregate early in embryogenesis.
      We have isolated pluripotent SSEA-1+ (stage-specific embryonic antigen-1+) cells
      from mice bone marrow using a MACS (magnetic-activated cell sorting) system. SSEA
      1+ cells were directly separated from the suspension of MMCs (murine mononuclear
      cells) harvested from bone marrow of 2-4-week-old mice. Flow-cytometry assay
      immediately after sorting and culturing under undifferentiated condition showed
      55+/-7% and 87+/-4% purity respectively. RT-PCR (reverse transcription-PCR)
      analysis after differentiation of SSEA-1+ cells into derivations of three germ
      layers showed the pluripotency properties of isolated cells. SSEA-1+ cells were
      induced to differentiate along germ cell lineage by adding BMP4 (bone morphogenic
      factor-4) to the medium. Regarding the expression of germ cell markers (PGCs,
      male and female germ cell lineage), it was found that adding exogenous BMP4 to
      culture medium could differentiate pluripotent SSEA-1+ cells isolated from an
      adult tissue into gamete precursors, PGCs. Differentiated cells expressed
      specific molecular markers of PGCs, including Oct4, fragilis, Stella and Mvh
      (mouse vasa homologue). Therefore BMP4 is insufficient to induce SSEA-1+ cells
      derived from PGCs to develop further into late germ cells in vitro.

PMID- 22988837
TI  - Early functional and transcriptomic changes in the myocardium predict outcome in
      a long-term rat model of sepsis.
AB  - Myocardial function is depressed in sepsis and is an important prognosticator in
      the human condition. Using echocardiography in a long-term fluid-resuscitated
      Wistar rat model of faecal peritonitis we investigated whether depressed
      myocardial function could be detected at an early stage of sepsis and, if so,
      whether the degree of depression could predict eventual outcome. At 6 h post
      insult, a stroke volume <0.17 ml prognosticated 3-day mortality with positive and
      negative predictive values of 93 and 80%, respectively. Subsequent fluid loading
      studies demonstrated intrinsic myocardial depression with poor-prognosis animals
      tolerating less fluid than either good-prognosis or sham-operated animals.
      Cardiac gene expression analysis at 6 h detected 527 transcripts significantly up
      or down-regulated by the septic process, including genes related to inflammatory
      and cell cycle pathways. Predicted mortality was associated with significant
      differences in transcripts of genes expressing proteins related to the TLR2/MyD88
      (Toll-like receptor 2/myeloid differentiation factor 88) and JAK/STAT (Janus
      kinase/signal transducer and activator of transcription) inflammatory pathways,
      beta-adrenergic signalling and intracellular calcium cycling. Our findings
      highlight the presence of myocardial depression in early sepsis and its
      prognostic significance. Transcriptomic analysis in heart tissue identified
      changes in signalling pathways that correlated with clinical dysfunction. These
      pathways merit further study to both better understand and potentially modify the
      disease process.

PMID- 22988838
TI  - A-to-I editing of protein coding and noncoding RNAs.
AB  - Adenosine deaminase acting on RNA (ADAR) catalyzes the hydrolytic deamination of
      adenosine to inosine in double-stranded RNA (dsRNA) substrates. Inosine pairs
      preferentially with cytidine, as opposed to uridine; therefore, ADAR editing
      alters the sequence and base pairing properties of both protein-coding and non
      coding RNA. Editing can directly alter the sequence of protein-coding transcripts
      and modify splicing, or affect a variety of non-coding targets, including
      microRNA, small interfering RNA, viral transcripts, and repeat elements such as
      Alu and LINE. Such editing has a wide range of physiological effects, including
      modification of targets in the brain and in disease states.

PMID- 22988839
TI  - Hematopoietic cytokines as tumor markers in gynecological malignancies. A
      multivariate analysis in epithelial ovarian cancer patients.
AB  - We investigated plasma levels of selected hematopoietic cytokines: stem cell
      factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating
      factor (M-CSF) and the tumor marker cancer antigen (CA 125) in epithelial ovarian
      cancer patients as compared with control groups: benign ovarian tumor patients
      (cysts) and healthy subjects. Cytokine levels were determined by enzyme-linked
      immunosorbent assay, CA 125 - using the chemiluminescent microparticle
      immunoassay method. Our results have demonstrated significant differences in the
      concentrations of M-CSF, G-CSF, SCF (with the exception of GM-CSF), and CA 125
      between the groups of ovarian cancer patients, cysts patients, and the healthy
      controls. When compared with CA 125, M-CSF has equal or higher values of
      diagnostic sensitivity and specificity. The M-CSF area under the receiver
      operating characteristic curve (AUC) was the largest from all the cytokines
      tested and slightly lower than the AUC of CA 125. These findings suggest the
      usefulness of M-CSF in diagnosing ovarian cancer, especially when discriminating
      between cancer and non-carcinoma lesions.

PMID- 22988840
TI  - Personal social network factors associated with overdose prevention training
      participation.
AB  - We investigated social network factors associated with participation in overdose
      prevention training among injection drug users (IDUs). From 2008 to 2010, 106
      IDUs who had witnessed an overdose in the past year from two syringe exchange
      programs in Los Angeles provided data on overdose prevention training status
      (trained vs. untrained), social networks, history of overdose, and demographics.
      In multivariate logistic regression, naming at least one network member who had
      been trained in overdose prevention was significantly associated with being
      trained (Adjusted Odds Ratio 3.25, 95% Confidence Interval 1.09, 9.68). Using
      social network approaches may help increase training participation. Limitations
      are noted.

PMID- 22988842
TI  - Limited-stage mantle cell lymphoma: not so different from advanced-stage.

PMID- 22988841
TI  - Maritrema orensense and Maritrema bonaerense (Digenea: Microphallidae):
      descriptions, life cycles, and comparative morphometric analyses.
AB  - We elucidate the life cycle of Maritrema orensense for the first time and
      experimentally confirm that of the sympatric Maritrema bonaerense. In Argentinean
      estuaries, both species parasitize the cochliopid snail Heleobia australis as
      first intermediate host, the grapsid crabs Neohelice granulata and Cyrtograpsus
      angulatus as second intermediate hosts, and gulls as definitive hosts. Here, we
      describe the daughter sporocysts and cercariae of M. orensense and redescribe
      these stages for M. bonaerense. Sporocysts of M. orensense are shorter, with
      fewer developed cercariae than M. bonaerense. The cercariae of M. orensense have
      longer, larger, and more undulating cephalic glands than M. bonaerense. We
      redescribe metacercariae and adults of both species and compare them with the
      previous descriptions. Intestinal ceca length, vitellaria shape and extension,
      and egg size are the most relevant characteristics in metacercariae and adults
      for differentiating the species. Hence, the detailed morphological description
      and comparative analyses of morphometrics obtained from natural and experimental
      infections permit clear differentiation of M. orensense and M. bonaerense at each
      life stage.

PMID- 22988843
TI  - Development of inhibitors as research tools for carbohydrate-processing enzymes.
AB  - Carbohydrates, which are present in all domains of life, play important roles in
      a host of cellular processes. These ubiquitous biomolecules form highly diverse
      and often complex glycan structures without the aid of a template. The
      carbohydrate structures are regulated solely by the location and specificity of
      the enzymes responsible for their synthesis and degradation. These enzymes,
      glycosyltransferases and glycoside hydrolases, need to be functionally well
      characterized in order to investigate the structure and function of glycans. The
      use of enzyme inhibitors, which target a particular enzyme, can significantly aid
      this understanding, and may also provide insights into therapeutic applications.
      The present article describes some of the approaches used to design and develop
      enzyme inhibitors as tools for investigating carbohydrate-processing enzymes.

PMID- 22988844
TI  - Synthesis of post-translationally modified proteins.
AB  - Post-translational modifications of proteins can have dramatic effect on the
      function of proteins. Significant research effort has gone into understanding the
      effect of particular modifications on protein parameters. In the present paper, I
      review some of the recently developed tools for the synthesis of proteins
      modified with single post-translational modifications at specific sites in the
      protein, such as amber codon suppression technologies, tag and modify, and native
      chemical ligation.

PMID- 22988845
TI  - Intrinsically disordered proteins: administration not executive.
AB  - IDPs (intrinsically disordered proteins) are common in eukaryotic genomes and
      have regulatory roles. In the cell, they are disordered, although not completely
      random. They bind weakly, but specifically, often remaining partially disordered
      even when bound. Whereas folded globular proteins have 'executive' roles in the
      cell, IDPs have an essential administrative function, making sure that the
      executive functions are properly co-ordinated. This makes them a good target for
      pharmaceutical intervention.

PMID- 22988846
TI  - Bacterial in-cell NMR of human alpha-synuclein: a disordered monomer by nature?
AB  - The notion that human alpha-synuclein is an intrinsically disordered monomeric
      protein was recently challenged by a postulated alpha-helical tetramer as the
      physiologically relevant protein structure. The fact that this alleged
      conformation had evaded detection for so many years was primarily attributed to a
      widely used denaturation protocol to purify recombinant alpha-synuclein. In the
      present paper, we provide in-cell NMR evidence obtained directly in intact
      Escherichia coli cells that challenges a tetrameric conformation under native in
      vivo conditions. Although our data cannot rule out the existence of other
      intracellular protein states, especially in cells of higher organisms, they
      indicate clearly that inside E. coli alpha-synuclein is mostly monomeric and
      disordered.

PMID- 22988847
TI  - Structural characterization of intrinsically disordered proteins by the combined
      use of NMR and SAXS.
AB  - In recent years, IDPs (intrinsically disordered proteins) have emerged as pivotal
      actors in biology. Despite IDPs being present in all kingdoms of life, they are
      more abundant in eukaryotes where they are involved in the vast majority of
      regulation and signalling processes. The realization that, in some cases,
      functional states of proteins were partly or fully disordered was in
      contradiction to the traditional view where a well defined three-dimensional
      structure was required for activity. Several experimental evidences indicate,
      however, that structural features in IDPs such as transient secondary-structural
      elements and overall dimensions are crucial to their function. NMR has been the
      main tool to study IDP structure by probing conformational preferences at residue
      level. Additionally, SAXS (small-angle X-ray scattering) has the capacity to
      report on the three-dimensional space sampled by disordered states and therefore
      complements the local information provided by NMR. The present review describes
      how the synergy between NMR and SAXS can be exploited to obtain more detailed
      structural and dynamic models of IDPs in solution. These combined strategies,
      embedded into computational approaches, promise the elucidation of the structure
      function properties of this important, but elusive, family of biomolecules.

PMID- 22988848
TI  - Diverse functional manifestations of intrinsic structural disorder in molecular
      chaperones.
AB  - IDPs (intrinsically disordered proteins) represent a unique class of proteins
      which show diverse molecular mechanisms in key biological functions. The aim of
      the present mini-review is to summarize IDP chaperones that have increasingly
      been studied in the last few years, by focusing on the role of intrinsic disorder
      in their molecular mechanism. Disordered regions in both globular and disordered
      chaperones are often involved directly in chaperone action, either by modulating
      activity or through direct involvement in substrate identification and binding.
      They might also be responsible for the subcellular localization of the protein.
      In outlining the state of the art, we survey known IDP chaperones discussing the
      following points: (i) globular chaperones that have an experimentally proven
      functional disordered region(s), (ii) chaperones that are completely disordered
      along their entire length, and (iii) the possible mechanisms of action of
      disordered chaperones. Through all of these details, we chart out how far the
      field has progressed, only to emphasize the long road ahead before the chaperone
      function can be firmly established as part of the physiological mechanistic
      arsenal of the emerging group of IDPs.

PMID- 22988849
TI  - Regulation of protein phosphatase 1 by intrinsically disordered proteins.
AB  - PP1 (protein phosphatase 1) is an essential serine/threonine phosphatase that
      plays a critical role in a broad range of biological processes, from muscle
      contraction to memory formation. PP1 achieves its biological specificity by
      forming holoenzymes with more than 200 known regulatory proteins. Interestingly,
      most of these regulatory proteins (>= 70%) belong to the class of IDPs
      (intrinsically disordered proteins). Thus structural studies highlighting the
      interaction of these IDP regulatory proteins with PP1 are an attractive model
      system because it allows general parameters for a group of diverse IDPs that
      interact with the same binding partner to be identified, while also providing
      fundamental insights into PP1 biology. The present review provides a brief
      overview of our current understanding of IDP-PP1 interactions, including the
      importance of pre-formed secondary and tertiary structures for PP1 binding, as
      well as changes of IDP dynamics upon interacting with PP1.

PMID- 22988850
TI  - Interplay between allostery and intrinsic disorder in an ensemble.
AB  - Allostery is a biological phenomenon of critical importance in metabolic
      regulation and cell signalling. The fundamental premise of classical models that
      describe allostery is that structure mediates 'action at a distance'. Recently,
      this paradigm has been challenged by the enrichment of IDPs (intrinsically
      disordered proteins) or ID (intrinsically disordered) segments in transcription
      factors and signalling pathways of higher organisms, where an allosteric response
      from external signals is requisite for regulated function. This observation
      strongly suggests that IDPs elicit the capacity for finely tunable allosteric
      regulation. Is there a set of transferable ground rules that reconcile these
      disparate allosteric phenomena? We focus on findings from the human GR
      (glucocorticoid receptor) which is a nuclear transcription factor in the SHR
      (steroid hormone receptor) family. GR contains an intrinsically disordered NTD (N
      terminal domain) that is obligatory for transcription activity. Different GR
      translational isoforms have various lengths of NTD and by studying these isoforms
      we found that the full-length ID NTD consists of two thermodynamically distinct
      coupled regions. The data are interpreted in the context of an EAM (ensemble
      allosteric model) that considers only the intrinsic and measurable energetics of
      allosteric systems. Expansion of the EAM is able to reconcile the paradox that
      ligands for SHRs can be agonists and antagonists in a cell-context-dependent
      manner. These findings suggest a mechanism by which SHRs in particular, and IDPs
      in general, may have evolved to couple thermodynamically distinct ID segments.
      The ensemble view of allostery that is illuminated provides organizing principles
      to unify the description of all allosteric systems and insight into 'how'
      allostery works.

PMID- 22988851
TI  - Cell cycle regulation by the intrinsically disordered proteins p21 and p27.
AB  - Today, it is widely accepted that proteins that lack highly defined globular
      three-dimensional structures, termed IDPs (intrinsically disordered proteins),
      play key roles in myriad biological processes. Our understanding of how intrinsic
      disorder mediates biological function is, however, incomplete. In the present
      paper, we review disorder-mediated cell cycle regulation by two intrinsically
      disordered proteins, p21 and p27. A structural adaptation mechanism involving a
      stretchable dynamic linker helix allows p21 to promiscuously recognize the
      various Cdk (cyclin-dependent kinase)-cyclin complexes that regulate cell
      division. Disorder within p27 mediates transmission of an N-terminal tyrosine
      phosphorylation signal to a C-terminal threonine phosphorylation, constituting a
      signalling conduit. These mechanisms are mediated by folding upon binding
      p21/p27's regulatory targets. However, residual disorder within the bound state
      contributes critically to these functional mechanisms. Our studies provide
      insights into how intrinsic protein disorder mediates regulatory processes and
      opportunities for designing drugs that target cancer-associated IDPs.

PMID- 22988852
TI  - Residual dipolar couplings measured in unfolded proteins are sensitive to amino
      acid-specific geometries as well as local conformational sampling.
AB  - Many functional proteins do not have well defined folded structures. In recent
      years, both experimental and computational approaches have been developed to
      study the conformational behaviour of this type of protein. It has been shown
      previously that experimental RDCs (residual dipolar couplings) can be used to
      study the backbone sampling of disordered proteins in some detail. In these
      studies, the backbone structure was modelled using a common geometry for all
      amino acids. In the present paper, we demonstrate that experimental RDCs are also
      sensitive to the specific geometry of each amino acid as defined by energy
      minimized internal co-ordinates. We have modified the FM (flexible-Meccano)
      algorithm that constructs conformational ensembles on the basis of a statistical
      coil model, to account for these differences. The modified algorithm inherits the
      advantages of the FM algorithm to efficiently sample the potential energy
      landscape for coil conformations. The specific geometries incorporated in the new
      algorithm result in a better reproduction of experimental RDCs and are generally
      applicable for further studies to characterize the conformational properties of
      intrinsically disordered proteins. In addition, the internal-co-ordinate-based
      algorithm is an order of magnitude more efficient, and facilitates side-chain
      construction, surface osmolyte simulation, spin-label distribution sampling and
      proline cis/trans isomer simulation.

PMID- 22988853
TI  - An intrinsically disordered protein, CP12: jack of all trades and master of the
      Calvin cycle.
AB  - Many proteins contain disordered regions under physiological conditions and lack
      specific three-dimensional structure. These are referred to as IDPs
      (intrinsically disordered proteins). CP12 is a chloroplast protein of
      approximately 80 amino acids and has a molecular mass of approximately 8.2-8.5
      kDa. It is enriched in charged amino acids and has a small number of hydrophobic
      residues. It has a high proportion of disorder-promoting residues, but has at
      least two (often four) cysteine residues forming one (or two) disulfide bridge(s)
      under oxidizing conditions that confers some order. However, CP12 behaves like an
      IDP. It appears to be universally distributed in oxygenic photosynthetic
      organisms and has recently been detected in a cyanophage. The best studied role
      of CP12 is its regulation of the Calvin cycle responsible for CO2 assimilation.
      Oxidized CP12 forms a supramolecular complex with two key Calvin cycle enzymes,
      GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and PRK (phosphoribulokinase),
      down-regulating their activity. Association-dissociation of this complex, induced
      by the redox state of CP12, allows the Calvin cycle to be inactive in the dark
      and active in the light. CP12 is promiscuous and interacts with other enzymes
      such as aldolase and malate dehydrogenase. It also plays other roles in plant
      metabolism such as protecting GAPDH from inactivation and scavenging metal ions
      such as copper and nickel, and it is also linked to stress responses. Thus CP12
      seems to be involved in many functions in photosynthetic cells and behaves like a
      jack of all trades as well as being a master of the Calvin cycle.

PMID- 22988854
TI  - LEA proteins: IDPs with versatile functions in cellular dehydration tolerance.
AB  - LEA (late embryogenesis abundant) proteins were originally described almost 30
      years ago as accumulating late in plant seed development. They were later found
      to be induced in vegetative plant tissues under environmental stress conditions
      and also in desiccation-tolerant micro-organisms and invertebrates. Although they
      are widely assumed to play crucial roles in cellular dehydration tolerance, their
      physiological and biochemical functions are largely unknown. Most LEA proteins
      are predicted to be intrinsically disordered and this has been experimentally
      verified in several cases. In addition, some LEA proteins partially fold, mainly
      into alpha-helices, during drying or in the presence of membranes. Recent studies
      have concentrated on the potential roles of LEA proteins in stabilizing membranes
      or sensitive enzymes during freezing or drying, and the present review
      concentrates on these two possible functions of LEA proteins in cellular
      dehydration tolerance.

PMID- 22988855
TI  - Mechanisms of small-molecule binding to intrinsically disordered proteins.
AB  - IDPs (intrinsically disordered proteins) play crucial roles in many important
      cellular processes such as signalling or transcription and are attractive
      therapeutic targets for several diseases. The considerable structural flexibility
      of IDPs poses a challenge for rational drug discovery approaches. Consequently,
      structure-based drug design efforts to date have mostly focused on inhibiting
      interactions of IDPs with other proteins whose structure can be solved by
      conventional biophysical methods. Yet, in recent years, several examples of small
      molecules that bind to monomeric IDPs in their disordered states have been
      reported, suggesting that this approach may offer new opportunities for
      therapeutic interventions. Further developments of this strategy will greatly
      benefit from an improved understanding of molecular recognition mechanisms
      between small molecules and IDPs. The present article summarizes findings from
      experimental and computational studies of the mechanisms of interaction between
      small molecules and three IDPs in their disordered states: c-Myc, Abeta (amyloid
      beta-peptide) and alpha-synuclein.

PMID- 22988856
TI  - Native disorder mediates binding of dynein to NudE and dynactin.
AB  - In the present paper, I report the molecular overlap of the linkage of three
      essential protein complexes that co-ordinate the formation of the mitotic
      spindle. These proteins are dynein, a large motor complex that moves machinery
      inside cells, and two of its regulators: a protein complex called dynactin, a
      dynein activator, and a protein called NudE whose depletion in mice produces a
      small brain and mental retardation. What is intriguing about the dynein-dynactin
      NudE interplay is that dynactin and NudE bind to a common segment of dynein that
      is intrinsically disordered. Elucidating differences in their binding modes may
      explain how one regulator can be selected over the other even when both are
      present in the same cellular compartment. These results not only have a far
      reaching impact on our understanding of processes essential for the formation and
      orientation of the spindle, but also offer a novel role for protein disorder in
      controlling cellular processes, and highlight the advantages of NMR spectroscopy
      in elucidating atomic-level characterization of extremely complex dynamic
      cellular assemblies.

PMID- 22988857
TI  - Using NMR chemical shifts to calculate the propensity for structural order and
      disorder in proteins.
AB  - NMR spectroscopy offers the unique possibility to relate the structural
      propensities of disordered proteins and loop segments of folded peptides to
      biological function and aggregation behaviour. Backbone chemical shifts are
      ideally suited for this task, provided that appropriate reference data are
      available and idiosyncratic sensitivity of backbone chemical shifts to structural
      information is treated in a sensible manner. In the present paper, we describe
      methods to detect structural protein changes from chemical shifts, and present an
      online tool [ncSPC (neighbour-corrected Structural Propensity Calculator)], which
      unites aspects of several current approaches. Examples of structural propensity
      calculations are given for two well-characterized systems, namely the binding of
      alpha-synuclein to micelles and light activation of photoactive yellow protein.
      These examples spotlight the great power of NMR chemical shift analysis for the
      quantitative assessment of protein disorder at the atomic level, and further our
      understanding of biologically important problems.

PMID- 22988858
TI  - Intrinsic disorder in proteins: a challenge for (un)structural biology met by ion
      mobility-mass spectrometry.
AB  - The link between structure and function of a given protein is a principal tenet
      of biology. The established approach to understand the function of a protein is
      to 'solve' its structure and subsequently investigate interactions between the
      protein and its binding partners. However, structure determination via
      crystallography or NMR is challenging for proteins where localized regions or
      even their entire structure fail to fold into a three-dimensional form. These so
      called IDPs (intrinsically disordered proteins) or intrinsically disordered
      regions constitute up to 40% of all expressed proteins, and a much higher
      percentage in proteins involved in the proliferation of cancer. For these
      proteins, there is a need to develop new methods for structural characterization
      which exploit their biophysical properties. IM (ion mobility)-MS is uniquely able
      to examine both absolute conformation(s), populations of conformation and also
      conformational change, and is therefore highly applicable to the study of IDPs.
      The present article details the technique of IM-MS and illustrates its use in
      assessing the relative disorder of the wild-type p53 DNA-core-binding domain of
      cellular tumour antigen p53. The IM data were acquired on a Waters Synapt HDMS
      instrument following nESI (nanoelectrospray ionization) from 'native' and low-pH
      solution conditions.

PMID- 22988859
TI  - Structures and interactions in 'bottlebrush' neurofilaments: the role of charged
      disordered proteins in forming hydrogel networks.
AB  - NFs (neurofilaments), the major cytoskeletal constituent of myelinated axons in
      vertebrates, consist of three different molecular-mass subunit proteins, NF-L
      (low), NF-M (medium) and NF-H (high), assembled to form mature filaments with
      protruding intrinsically disordered C-terminal side-arms. Liquid crystal gel
      networks of side-arm-mediated NF assemblies play a key role in the mechanical
      stability of neuronal processes. Disruptions of the NF network, due to NF
      overaccumulation or incorrect side-arm interactions, are a hallmark of motor
      neuron diseases including amyotrophic lateral sclerosis. Using synchrotron small
      angle X-ray scattering and various microscopy techniques, we have investigated
      the role of the peptide charges in the subunit side-arms on the structure and
      interaction of NFs. Our findings, which delineate the distinct roles of NF-M and
      NF-H in regulating NF interactions, shed light on possible mechanisms of
      disruption of optimal mechanical network properties.

PMID- 22988860
TI  - Evolutionary selection for protein aggregation.
AB  - Protein aggregation is being found to be associated with an increasing number of
      human diseases. Aggregation can lead to a loss of function (lack of active
      protein) or to a toxic gain of function (cytotoxicity associated with protein
      aggregates). Although potentially harmful, protein sequences predisposed to
      aggregation seem to be ubiquitous in all kingdoms of life, which suggests an
      evolutionary advantage to having such segments in polypeptide sequences. In fact,
      aggregation-prone segments are essential for protein folding and for mediating
      certain protein-protein interactions. Moreover, cells use protein aggregates for
      a wide range of functions. Against this background, life has adapted to tolerate
      the presence of potentially dangerous aggregation-prone sequences by constraining
      and counteracting the aggregation process. In the present review, we summarize
      the current knowledge of the advantages associated with aggregation-prone
      stretches in proteomes and the strategies that cellular systems have developed to
      control the aggregation process.

PMID- 22988861
TI  - Deciphering the function of leucine-rich repeat kinase 2 and targeting its
      dysfunction in disease.
AB  - LRRK2 (leucine-rich repeat kinase 2) is a gene of unknown function that has been
      linked to a number a human diseases, including PD (Parkinson's disease), IBD
      (inflammatory bowel disease), leprosy and cancer. The papers from the LRRK2:
      Function and Dysfunction meeting in this issue of Biochemical Society
      Transactions explore our growing knowledge of LRRK2's normal function, the role
      that it plays in disease and emerging strategies to exploit LRRK2 as a
      therapeutic target.

PMID- 22988862
TI  - Genetic analysis of Parkinson's disease-linked leucine-rich repeat kinase 2.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common genetic
      cause of PD (Parkinson's disease). To investigate how mutations in LRRK2 cause
      PD, we generated LRRK2 mutant mice either lacking its expression or expressing
      the R1441C mutant form. Homozygous R1441C knockin mice exhibit no dopaminergic
      neurodegeneration or alterations in steady-state levels of striatal dopamine, but
      they show impaired dopamine neurotransmission, as was evident from reductions in
      amphetamine-induced locomotor activity and stimulated catecholamine release in
      cultured chromaffin cells as well as impaired dopamine D2 receptor-mediated
      functions. Whereas LRRK2-/- brains are normal, LRRK2-/- kidneys at 20 months of
      age develop striking accumulation and aggregation of alpha-synuclein and
      ubiquitinated proteins, impairment of the autophagy-lysosomal pathway, and
      increases in apoptotic cell death, inflammatory responses and oxidative damage.
      Our further analysis of LRRK2-/- kidneys at multiple ages revealed unique age
      dependent biphasic alterations of the autophagic activity, which is unchanged at
      1 month of age, enhanced at 7 months, but reduced at 20 months. Levels of alpha
      synuclein and protein carbonyls, a general oxidative damage marker, are also
      decreased in LRRK2-/- kidneys at 7 months of age. Interestingly, this biphasic
      alteration is associated with increased levels of lysosomal proteins and
      proteases as well as progressive accumulation of autolysosomes and lipofuscin
      granules. We conclude that pathogenic mutations in LRRK2 impair the nigrostriatal
      dopaminergic pathway, and LRRK2 plays an essential role in the dynamic regulation
      of autophagy function in vivo.

PMID- 22988863
TI  - The synaptic function of LRRK2.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most frequent genetic
      lesions so far found in familial as well as sporadic forms of PD (Parkinson's
      disease), a neurodegenerative disease characterized by the dysfunction and
      degeneration of dopaminergic and other neuronal types. The molecular and cellular
      mechanisms underlying LRRK2 action remain poorly defined. Synaptic dysfunction
      has been increasingly recognized as an early event in the pathogenesis of major
      neurological disorders. Using Drosophila as a model system, we have shown that
      LRRK2 controls synaptic morphogenesis. Loss of dLRRK (Drosophila LRRK2) results
      in synaptic overgrowth at the Drosophila neuromuscular junction synapse, whereas
      overexpression of wild-type dLRRK, hLRRK2 (human LRRK2) or the pathogenic hLRRK2
      G2019S mutant has the opposite effect. Alteration of LRRK2 activity also affects
      synaptic transmission in a complex manner. LRRK2 exerts its effects on synaptic
      morphology by interacting with distinct downstream effectors at the pre- and post
      synaptic compartments. At the postsynapse, LRRK2 functionally interacts with 4E
      BP (eukaryotic initiation factor 4E-binding protein) and the microRNA machinery,
      both of which negatively regulate protein synthesis. At the presynapse, LRRK2
      phosphorylates and negatively regulates the microtubule-binding protein Futsch
      and functionally interacts with the mitochondrial transport machinery. These
      results implicate compartment-specific synaptic dysfunction caused by altered
      protein synthesis, cytoskeletal dynamics and mitochondrial transport in LRRK2
      pathogenesis and offer a new paradigm for understanding and ultimately treating
      LRRK2-related PD.

PMID- 22988864
TI  - Biochemical and functional characterization of the ROC domain of DAPK establishes
      a new paradigm of GTP regulation in ROCO proteins.
AB  - DAPK (death-associated protein kinase) is a newly recognized member of the
      mammalian family of ROCO proteins, characterized by common ROC (Ras of complex
      proteins) and COR (C-terminal of ROC) domains. In the present paper, we review
      our recent work showing that DAPK is functionally a ROCO protein; its ROC domain
      binds and hydrolyses GTP. Furthermore, GTP binding regulates DAPK catalytic
      activity in a novel manner by enhancing autophosphorylation on inhibitory Ser308,
      thereby promoting the kinase 'off' state. This is a novel mechanism for in cis
      regulation of kinase activity by the distal ROC domain. The functional
      similarities between DAPK and the Parkinson's disease-associated protein LRRK2
      (leucine-rich repeat protein kinase 2), another member of the ROCO family, are
      also discussed.

PMID- 22988865
TI  - Role of LRRK2 kinase activity in the pathogenesis of Parkinson's disease.
AB  - Interest in studying the biology of LRRK2 (leucine-rich repeat kinase 2) started
      in 2004 when missense mutations in the LRRK2 gene were linked to an inherited
      form of Parkinson's disease with clinical and pathological presentation
      resembling the sporadic syndrome. LRRK2 is a complex molecule containing domains
      implicated in protein interactions, as well as kinase and GTPase activities. The
      observation that the common G2019S mutation increases kinase activity in vitro
      suggests that altered phosphorylation of LRRK2 targets may have pathological
      outcomes. Given that protein kinases are ideal targets for drug therapies, much
      effort has been directed at understanding the role of LRRK2 kinase activity on
      disease onset. However, no clear physiological substrates have been identified to
      date, indicating that much research is still needed to fully understand the
      signalling pathways orchestrated by LRRK2 and deregulated under pathological
      conditions.

PMID- 22988866
TI  - The GTPase function of LRRK2.
AB  - LRRK2 (leucine-rich repeat kinase 2) is a large protein encoding multiple
      functional domains, including two catalytically active domains, a kinase and a
      GTPase domain. The LRRK2 GTPase belongs to the Ras-GTPase superfamily of GTPases,
      more specifically to the ROC (Ras of complex proteins) subfamily. Studies with
      recombinant LRRK2 protein purified from eukaryotic cells have confirmed that
      LRRK2 binds guanine nucleotides and catalyses the hydrolysis of GTP to GDP. LRRK2
      is linked to PD (Parkinson's disease) and GTPase activity is impaired for several
      PD mutants located in the ROC and COR (C-terminal of ROC) domains, indicating
      that it is involved in PD pathogenesis. Ras family GTPases are known to function
      as molecular switches, and several studies have explored this possibility for
      LRRK2. These studies show that there is interplay between the LRRK2 GTPase
      function and its kinase function, with most data pointing towards a role for the
      kinase domain as an upstream regulator of ROC. The GTPase function is therefore a
      pivotal functionality within the LRRK2-mediated signalling cascade which includes
      partners encoded by other LRRK2 domains as well as other cellular signalling
      partners. The present review examines what is known of the enzymatic properties
      of the LRRK2 GTPase, the interplay between ROC and other LRRK2 domains, and the
      interplay between ROC and other cellular proteins with the dual goal to
      understand how LRRK2 GTPase affects cellular functions and point to future
      research venues.

PMID- 22988867
TI  - Cellular effects of LRRK2 mutations.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) are a relatively common cause
      of inherited PD (Parkinson's disease), but the mechanism(s) by which mutations
      lead to disease are poorly understood. In the present paper, I discuss what is
      known about LRRK2 in cellular models, focusing specifically on assays that have
      been used to tease apart the effects of LRRK2 mutations on cellular phenotypes.
      LRRK2 expression has been suggested to cause loss of neuronal viability, although
      because it also has a strong effect on the length of neurites on these cells,
      whether this is true toxicity or not is unclear. Also, LRRK2 mutants can promote
      the redistribution of LRRK2 from diffuse cytosolic staining to more discrete
      structures, at least at high expression levels achieved in transfection
      experiments. The relevance of these phenotypes for PD is not yet clear, and a
      great deal of work is needed to understand them in more depth.

PMID- 22988869
TI  - Insights into LRRK2 function and dysfunction from transgenic and knockout rodent
      models.
AB  - Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene on chromosome 12 cause
      autosomal dominant PD (Parkinson's disease), which is indistinguishable from
      sporadic forms of the disease. Numerous attempts have therefore been made to
      model PD in rodents via the transgenic expression of LRRK2 and its mutant
      variants and to elucidate the function of LRRK2 by knocking out rodent Lrrk2.
      Although these models often only partially recapitulate PD pathology, they have
      helped to elucidate both the normal and pathological function of LRRK2. In
      particular, LRRK2 has been suggested to play roles in cytoskeletal dynamics,
      synaptic machinery, dopamine homoeostasis and autophagic processes. Our
      understanding of how these pathways are affected, their contribution towards PD
      development and their interaction with one another is still incomplete, however.
      The present review summarizes the findings from LRRK2 rodent models and draws
      potential connections between the apparently disparate cellular processes
      altered, in order to better understand the underlying mechanisms of LRRK2
      dysfunction and illuminate future therapeutic interventions.

PMID- 22988868
TI  - LRRK2 GTPase dysfunction in the pathogenesis of Parkinson's disease.
AB  - Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene are the most frequent
      genetic cause of PD (Parkinson's disease), and these mutations play important
      roles in sporadic PD. The LRRK2 protein contains GTPase and kinase domains and
      several protein-protein interaction domains. The kinase and GTPase activity of
      LRRK2 seem to be important in regulating LRRK2-dependent cellular signalling
      pathways. LRRK2's GTPase and kinase domains may reciprocally regulate each other
      to direct LRRK2's ultimate function. Although most LRRK2 investigations are
      centred on LRRK2's kinase activity, the present review focuses on the function of
      LRRK2's GTPase activity in LRRK2 physiology and pathophysiology.

PMID- 22988870
TI  - Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number
      and sites of Parkinson's disease mutations.
AB  - Various investigators have identified the major domain organization of LRRK2
      (leucine-rich repeat kinase 2), which includes a GTPase ROC (Ras of complex
      proteins) domain followed by a COR (C-terminal of ROC) domain and a protein
      kinase domain. In addition, there are four domains composed of structural repeat
      motifs likely to be involved in regulation and localization of this complex
      protein. In the present paper, we report our bioinformatic analyses of the human
      LRRK2 amino acid sequence to predict the repeat size, number and likely
      boundaries for the armadillo repeat, ankyrin repeat, the leucine-rich repeat and
      WD40 repeat regions of LRRK2. Homology modelling using known protein structures
      with similar domains was used to predict structures, exposed residues and
      location of mutations for these repeat regions. We predict that the armadillo
      repeats, ankyrin repeats and leucine-rich repeats together form an extended N
      terminal flexible 'solenoid'-like structure composed of tandem repeat modules
      likely to be important in anchoring to the membrane and cytoskeletal structures
      as well as binding to other protein ligands. Near the C-terminus of LRRK2, the
      WD40 repeat region is predicted to form a closed propeller structure that is
      important for protein complex formation.

PMID- 22988871
TI  - MASL1: a neglected ROCO protein.
AB  - The human ROCO proteins are a family of four proteins characterized by a
      conserved supradomain: a Ras-like GTPase domain. This domain consists of ROC (Ras
      of complex proteins) occurring in tandem with a COR (C-terminal of ROC) domain.
      Together, these proteins are linked to various pathologies including cancer and
      PD (Parkinson's disease). Despite an increasing research focus on these proteins,
      their functions in general, and their specific roles in disease, are still
      unknown. In the case of MASL1 (malignant fibrous histiocytoma amplified sequences
      with leucine-rich tandem repeats 1), a predicted oncoprotein in MFHs (malignant
      fibrous histiocytomas), there is a particular lack of information available in
      the literature. The aim of the present review is therefore to summarize the
      existing information on MASL1 and also to compile data that could be linked to
      MASL1 and thus help our understanding of this neglected ROCO protein.

PMID- 22988872
TI  - Human leucine-rich repeat kinase 1 and 2: intersecting or unrelated functions?
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) are associated with both
      familial and sporadic PD (Parkinson's disease). LRRK1 (leucine-rich repeat kinase
      1) shares a similar domain structure with LRRK2, but it is not linked to PD. LRRK
      proteins belong to a gene family known as ROCO, which codes for large proteins
      with several domains. All ROCO proteins have a ROC (Ras of complex proteins)
      GTPase domain followed by a domain of unknown function [COR (C-terminal of ROC)].
      LRRK2, LRRK1 and other ROCO proteins also possess a kinase domain. To date, the
      function of LRRK1 and both the physiological and the pathological roles of LRRK2
      are only beginning to unfold. The comparative analysis of these two proteins is a
      strategy to single out the specific properties of LRRKs to understand their
      cellular physiology. This comparison is the starting point to unravel the
      pathways that may lead to PD and eventually to develop therapeutic strategies for
      its treatment. In the present review, we discuss recently published results on
      LRRK2 and its paralogue LRRK1 concerning their evolutionary significance,
      biochemical properties and potential functional roles.

PMID- 22988873
TI  - Phosphorylation of LRRK2: from kinase to substrate.
AB  - The PD (Parkinson's disease) protein LRRK2 (leucine-rich repeat kinase 2) occurs
      in cells as a highly phosphorylated protein, with the majority of phosphosites
      clustering in the region between the ankyrin repeat and leucine-rich repeat
      domains. The observation that several pathogenic variants of LRRK2 display
      strongly reduced cellular phosphorylation suggests that phosphorylation of LRRK2
      is involved in the PD pathological process. Furthermore, treatment of cells with
      inhibitors of LRRK2 kinase activity, which are currently considered as potential
      disease-modifying therapeutics for PD, leads to a rapid decrease in the
      phosphorylation levels of LRRK2. For these reasons, understanding the cellular
      role and regulation of LRRK2 as a kinase and as a substrate has become the focus
      of intense investigation. In the present review, we discuss what is currently
      known about the cellular phosphorylation of LRRK2 and how this relates to its
      function and dysfunction.

PMID- 22988874
TI  - Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2.
AB  - PD (Parkinson's disease) is a common neurodegenerative disease clinically
      characterized by bradykinesia, rigidity and resting tremor. Recent studies have
      proposed that synaptic dysfunction, implicated in numerous studies of animal
      models of PD, might be a key factor in PD. The molecular defects that lead to PD
      progression might be hidden at the presynaptic neuron: in fact accumulating
      evidence has shown that the majority of the genes linked to PD play a critical
      role at the presynaptic site. In the present paper, we focus on the presynaptic
      function of LRRK2 (leucine-rich repeat kinase 2), a protein that mutated
      represents the main genetic cause of familial PD described to date.
      Neurotransmission relies on proper presynaptic vesicle trafficking; defects in
      this process, variation in dopamine flow and alteration of presynaptic plasticity
      have been reported in several animal models of LRRK2 mutations. Furthermore,
      impaired dopamine turnover has been described in presymptomatic LRRK2 PD
      patients. Thus, given the pathological events occurring at the synapses of PD
      patients, the presynaptic site may represent a promising target for early
      diagnostic therapeutic intervention.

PMID- 22988875
TI  - LRRK2 and vesicle trafficking.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) (also known as PARK8 or
      dardarin) are responsible for the autosomal-dominant form of PD (Parkinson's
      disease). LRRK2 mutations were found in approximately 3-5% of familial and 1-3%
      of sporadic PD cases with the highest prevalence (up to 40%) in North Africans
      and Ashkenazi Jews. To date, mutations in LRRK2 are a major genetic risk factor
      for familial and sporadic PD. Despite the fact that 8 years have passed from the
      establishment of the first link between PD and dardarin in 2004, the
      pathophysiological role of LRRK2 in PD onset and progression is far from clearly
      defined. Also the generation of different LRRK2 transgenic or knockout animals
      has not provided new hints on the function of LRRK2 in the brain. The present
      paper reviews recent evidence regarding a potential role of LRRK2 in the
      regulation of membrane trafficking from vesicle generation to the movement along
      cytoskeleton and finally to vesicle fusion with cell membrane.

PMID- 22988876
TI  - The importance of Wnt signalling for neurodegeneration in Parkinson's disease.
AB  - PD (Parkinson's disease) is a devastating progressive motor disorder with no
      available cure. Over the last two decades, an increasing number of genetic
      defects have been found that cause familial and idiopathic forms of PD. In
      parallel, the importance of Wnt signalling pathways for the healthy functioning
      of the adult brain and the dysregulation of these pathways in neurodegenerative
      disease has become apparent. Cell biological functions disrupted in PD are
      partially controlled by Wnt signalling pathways and proteins encoded by PARK
      genes have been shown to modify Wnt signalling. This suggests the prospect of
      targeting Wnt signalling pathways to modify PD progression.

PMID- 22988877
TI  - Possible involvement of the relationship of LRRK2 and autophagy in Parkinson's
      disease.
AB  - PD (Parkinson's disease) is a neurodegenerative disorder caused by loss of
      dopamine-generating cells in the substantia nigra. The implication of genetic
      factors in the aetiology of PD has an essential importance in our understanding
      of the development of the disease. Mutations in the LRRK2 (leucine-rich repeat
      kinase 2) gene cause late-onset PD with a clinical appearance indistinguishable
      from idiopathic PD. Moreover, LRRK2 has been associated with the process of
      autophagy regulation. Autophagy is an intracellular catabolic mechanism whereby a
      cell recycles or degrades damaged proteins and cytoplasmic organelles. In the
      present paper, we discuss the role of LRRK2 in autophagy, and the importance of
      this relationship in the development of nigral degeneration in PD.

PMID- 22988878
TI  - An emerging role for LRRK2 in the immune system.
AB  - Missense mutations in LRRK2 (leucine-rich repeat kinase 2) contribute
      significantly to autosomal dominant PD (Parkinson's disease). Genome-wide
      association studies have suggested further that mutations in LRRK2 comprise a
      risk factor for sporadic PD. How LRRK2 contributes to PD, however, is largely
      unknown. Recent work has shown that LRRK2 is highly expressed in tissue and
      circulating immune cells and is suggestive of a potential role for LRRK2 in
      innate immunity. These studies and their potential implications for PD are
      discussed in the present paper.

PMID- 22988879
TI  - A link between LRRK2, autophagy and NAADP-mediated endolysosomal calcium
      signalling.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) represent a significant
      component of both sporadic and familial PD (Parkinson's disease). Pathogenic
      mutations cluster in the enzymatic domains of LRRK2, and kinase activity seems to
      correlate with cytotoxicity, suggesting the possibility of kinase-based
      therapeutic strategies for LRRK2-associated PD. Apart from cytotoxicity, changes
      in autophagy have consistently been observed upon overexpression of mutant, or
      knockdown of endogenous, LRRK2. However, delineating the precise mechanism(s) by
      which LRRK2 regulates autophagy has been difficult. Recent data suggest a
      mechanism involving late steps in autophagic-lysosomal clearance in a manner
      dependent on NAADP (nicotinic acid-adenine dinucleotide phosphate)-sensitive
      lysosomal Ca2+ channels. In the present paper, we review our current knowledge of
      the link between LRRK2 and autophagic-lysosomal clearance, including regulation
      of Ca2+-dependent events involving NAADP.

PMID- 22988880
TI  - LRRK2 and autophagy: a common pathway for disease.
AB  - LRRK2 (leucine-rich repeat kinase 2) is an enzyme implicated in human disease,
      containing kinase and GTPase functions within the same multidomain open reading
      frame. Dominant mutations in the LRRK2 gene are the most common cause of familial
      PD (Parkinson's disease). Additionally, in genome-wide association studies, the
      LRRK2 locus has been linked to risk of PD, Crohn's disease and leprosy, and LRRK2
      has also been linked with cancer. Despite its association with human disease,
      very little is known about its pathophysiology. Recent reports suggest a
      functional association between LRRK2 and autophagy. Implications of this set of
      data for our understanding of LRRK2's role in physiology and disease are
      discussed in the present paper.

PMID- 22988881
TI  - Cellular reprogramming: a new approach to modelling Parkinson's disease.
AB  - iPSCs (induced pluripotent stem cells) offer an unparalleled opportunity to
      generate and study physiologically relevant cell types in culture. iPSCs can be
      generated by reprogramming almost any somatic cell type using pluripotency
      factors such as Oct4, SOX2, Nanog and Klf4. By reprogramming cells from patients
      carrying disease-associated mutations, and subsequent differentiation into the
      cell type of interest, researchers now have the opportunity to study disease
      specific cell types which were previously inaccessible. In the case of PD
      (Parkinson's disease), reprogramming is advancing rapidly, and cell lines have
      been generated from patients carrying mutations in several disease-associated
      genes, including SNCA (alpha-synuclein), PARK2 (parkin), PINK1 (phosphatase and
      tensin homologue deleted on chromosome 10-induced putative kinase 1), PARK7 (DJ
      1) and LRRK2 (leucine-rich repeat kinase 2), as well as idiopathic cases.
      Functional dopaminergic neurons have been differentiated from these cells and
      their physiology has been compared with control neurons. Human dopaminergic
      neurons had been previously inaccessible until post-mortem, when the disease is
      generally highly progressed into pathology. In comparison, iPSCs provide a living
      cell model with the potential to study early molecular changes which accumulate
      in cells and ultimately result in neurodegeneration. Although clear phenotypes
      have not yet been unambiguously identified in patient-derived dopaminergic
      neurons, there are suggested aberrations in cellular pathways involved in
      neurodegeneration. Overall, these cells offer a unique opportunity to study
      dopaminergic neurons carrying a 'Parkinsonian genome'. The present review
      discusses the advances in cellular reprogramming technologies and studies that
      have been carried out on PD-derived iPSCs and differentiated dopaminergic
      neurons.

PMID- 22988882
TI  - Pharmacological inhibition of LRRK2 cellular phosphorylation sites provides
      insight into LRRK2 biology.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) have been linked to inherited
      forms of PD (Parkinson's disease). Substantial pre-clinical research and drug
      discovery efforts have focused on LRRK2 with the hope that small-molecule
      inhibitors of the enzyme may be valuable for the treatment or prevention of the
      onset of PD. The pathway to develop therapeutic or neuroprotective agents based
      on LRRK2 function (i.e. kinase activity) has been facilitated by the development
      of both biochemical and cell-based assays for LRRK2. LRRK2 is phosphorylated on
      Ser910, Ser935, Ser955 and Ser973 in the N-terminal domain of the enzyme, and
      these sites of phosphorylation are likely to be regulated by upstream enzymes in
      an LRRK2 kinase-activity-dependent manner. Knowledge of these phosphorylation
      sites and their regulation can be adapted to high-throughput-screening-amenable
      platforms. The present review describes the utilization of LRRK2 phosphorylation
      as indicators of enzyme inhibition, as well as how such assays can be used to
      deconvolute the pathways in which LRRK2 plays a role.

PMID- 22988883
TI  - Covalent attachment of biomacromolecules to plasma-patterned and functionalized
      carbon nanotube-based devices for electrochemical biosensing.
AB  - The interface between biomacromolecules and carbon nanotubes (CNTs) is of
      critical importance in developing effective techniques that provide CNTs with
      both biomolecular recognition and signal transduction through immobilization.
      However, the chemical inertness of CNT surfaces poses an obstacle to wider
      implementation of CNTs in bioanalytical applications. In this paper, we present a
      review of our recent research activities related to the covalent attachment of
      biomacromolecules to plasma-patterned and functionalized carbon nanotube films
      and their application to the fabrication of electrochemical biosensing devices.
      The SWCNT films were spray-deposited onto a miniaturized three-electrode system
      on a glass substrate and activated using highly purified atomic oxygen generated
      in radiofrequency plasma; this introduced oxygen-containing functional groups
      into the SWCNT surface without fatal loss of the original physicochemical
      properties of the CNTs. The carboxylated SWCNT electrodes were then selectively
      modified via amidation or esterification for covalent immobilization of the
      biomacromolecules. The plasma-treated SWCNT-based sensing electrode had an
      approximately six times larger effective area than the untreated SWCNT-based
      electrode, which significantly amplified the amperometric electrochemical signal.
      Finally, the efficacy of plasma-functionalized SWCNT (pf-SWCNT) as a biointerface
      was examined by immobilizing glucose oxidase, Legionella pneumophila ( L.
      pneumophila)-specific antibodies, L. pneumophila-originated DNAs, and thrombin
      specific aptamers on the pf-SWCNT-based three-electrode devices. The pf-SWCNT
      films were found to support direct covalent immobilization of the above-listed
      biomacromolecules on the films and to thereby overcome the many drawbacks
      typically associated with simple physisorption. Thus, pf-SWCNT sensing electrodes
      on which biomacromolecules were covalently immobilized were found to be
      chemically stable and have a long lifetime.

PMID- 22988884
TI  - Isolation of thuridillins D-F, diterpene metabolites from the Australian
      sacoglossan mollusk Thuridilla splendens; relative configuration of the
      epoxylactone ring.
AB  - This first chemical study of the sacoglossan mollusk Thuridilla splendens from
      Mooloolaba, South East Queensland, has resulted in the isolation of three new
      metabolites, thuridillins D-F (1-3), and one known metabolite, thuridillin A (4).
      Thuridillin D (1) was isolated by conventional flash chromatography on silica
      gel, while a mixture of thuridillins E (2) and F (3) was obtained by PTLC on
      AgNO(3)-impregnated silica gel. Thuridillins D-F were determined to be
      structurally related to thuridillin B (5); 1 possessed a hydroxy group at C-11,
      and 2 and 3 were Delta(10,11)- and Delta(11,12)-isomers, respectively. HSQC
      HECADE NMR data, together with conformational analysis, NOESY experiments, and
      (1)H-(1)H coupling studies enabled assignment of the individual relative
      configurations of the epoxylactone, the 2,5-diacetoxy-2,5-dihydrofuran, and
      cyclohexyl moieties within thuridillin D (1).

PMID- 22988885
TI  - Constructing multiplicative measures of beliefs in the theory of planned
      behaviour.
AB  - OBJECTIVE: Commonly used theories in health psychology involve multiplicative
      composites of measures, which have been used as predictors, mediators, and
      outcomes. The chosen scaling system can affect correlations with other variables.
      This study evaluated how best to construct composites in the context of the
      theory of planned behaviour (TPB), using hierarchical linear regression, a priori
      defined scaling systems, and optimal scaling. DESIGN: Longitudinal. METHODS: At
      baseline, 6 and 12 months, 365 trial participants (ProActive) completed
      questionnaires assessing salient beliefs, which were used to construct composites
      (indirect measures), and direct measures of instrumental and affective attitude,
      subjective norm, and perceived behavioural control towards becoming more
      physically active over the next 12 months. RESULTS: Linear regression supported a
      multiplicative model for indirect instrumental attitude and perceived control.
      Except for perceived control, associations between composites and direct measures
      were unaffected by different a priori scaling systems. Optimal scaling produced
      widely differing composites over time for subjective norm and affective attitude
      and a negative association between composite and direct measure for subjective
      norm. CONCLUSIONS: We recommend that researchers who use multiplicative
      composites first establish clear support for a multiplicative model, before they
      examine a range of meaningful scaling systems on theoretical and empirical
      grounds. Caution is needed when using optimal scaling without checking that a
      multiplicative model is supported and the resulting scaling system meaningful.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? Multiplicative
      composites are included in commonly used theories in health psychology (e.g.,
      theory of planned behaviour). Valid measures are needed as the choice of scaling
      system (e.g., unipolar or bipolar) can affect estimates of associations between
      composites and other variables. Ajzen has advocated the use of optimal scaling.
      What does this study add? The study shows that optimal scaling can result in
      meaningless measures. We recommend that health psychologists use optimal scaling
      with great caution and we provide alternative recommendations for constructing
      composites.

PMID- 22988886
TI  - Intracranial evaluation of the epileptogenic zone in regional infrasylvian
      polymicrogyria.
AB  - PURPOSE: To define the relationship between the epileptogenic zone and the
      polymicrogyric area using intracranial electroencephalography (EEG) recordings in
      patients with structural epilepsy associated with regional infrasylvian
      polymicrogyria (PMG). METHODS: We retrospectively reviewed the medical charts,
      scalp, and intracranial video-EEG recordings, neuroimaging findings, and
      neuropsychological evaluations of four patients with refractory temporal lobe
      epilepsy related to PMG who consequently underwent resective surgery. KEY
      FINDINGS: High-resolution magnetic resonance imaging (MRI) revealed temporal lobe
      PMG in all cases, accompanied by hippocampal malrotation and closed lip
      schizencephaly in 3/4 cases, respectively. In intracranial recordings, interictal
      spike activity was localized within the PMG in only 2/4 and within the amygdala,
      hippocampus, and entorhinal cortex in all cases. In the first patient, two
      epileptogenic networks coexisted: the prevailing network initially involved the
      mesial temporal structures with spread to the anterior PMG; the secondary network
      successively involved the anterior part of the PMG and later the mesial temporal
      structures. In the second patient, the epileptogenic network was limited to the
      mesial temporal structures, fully sparing the PMG. In the third patient, the
      epileptogenic network first involved the mesial temporal structures and later the
      PMG. Conversely, in the last case, part of the PMG harbored an epileptogenic
      network that propagated to the mesial temporal structures. Consistent with these
      findings a favorable outcome (Engel class I in three of four patients; Engel
      class II in one of four) at last follow-up was obtained by a resection involving
      parts of the PMG cortex in three of four and anteromesial temporal lobe
      structures in another three of four cases. SIGNIFICANCE: Infrasylvian PMG
      displays a heterogeneous epileptogenicity and is occasionally and partially
      involved in the epileptogenic zone that commonly includes the mesial temporal
      structures. Our results highlight the intricate interrelations between the MRI
      detectable lesion and the epileptogenic zone as delineated by intracranial
      recordings. Seizure freedom can be accomplished as a result of a meticulous
      intracranial study guiding a tailored resection that may spare part of the PMG.

PMID- 22988887
TI  - Application of the Hubbard model to Cp*(2)Yb(bipy), a model system for strong
      exchange coupling in lanthanide systems.
AB  - Exchange coupling is quantified in lanthanide (Ln) single-molecule magnets (SMMs)
      containing a bridging N(2)(3-) radical ligand and between [Cp*(2)Yb](+) and
      bipy(*-) in Cp*(2)Yb(bipy), where Cp* is pentamethylcyclopentadienyl and bipy is
      2,2'-bipyridyl. In the case of these lanthanide SMMs, the magnitude of exchange
      coupling between the Ln ion and the bridging N(2)(3-), 2J, is very similar to the
      barrier to magnetic relaxation, U(eff). A molecular version of the Hubbard model
      is applied to systems in which unpaired electrons on magnetic metal ions have
      direct overlap with unpaired electrons residing on ligands. The Hubbard model
      explicitly addresses electron correlation, which is essential for understanding
      the magnetic behavior of these complexes. This model is applied quantitatively to
      Cp*(2)Yb(bipy) to explain its very strong exchange coupling, 2J = -0.11 eV (-920
      cm(-1)). The model is also used to explain the presence of strong exchange
      coupling in Ln SMMs in which the lanthanide spins are coupled via bridging N(2)(3
      ) radical ligands. The results suggest that increasing the magnetic coupling in
      lanthanide clusters could lead to an increase in the blocking temperatures of
      exchange-coupled lanthanide SMMs, suggesting routes to  rational design of future
      lanthanide SMMs.

PMID- 22988888
TI  - Obstructive sleep apnoea and the risk of type 2 diabetes: a meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND AND OBJECTIVE: There has been increasing recognition that obstructive
      sleep apnoea (OSA) is associated with incident type 2 diabetes. The aim of this
      study was to assess the association between the severity of OSA and the risk of
      type 2 diabetes by performing a meta-analysis of all available prospective cohort
      studies. METHODS: A search was conducted of the PubMed, EMBASE, CINAHL and ISI
      Web of Knowledge databases through March 2012 to identify studies linking OSA
      with the risk of diabetes. Only prospective cohort studies, in which the presence
      of OSA was confirmed by objective measurements, were included. Fixed and random
      effects models were used to calculate pooled relative risks (RR). RESULTS: This
      meta-analysis of six prospective cohort studies including a total of 5953
      participants, with follow-up periods of 2.7-16 years, and 332 incident cases of
      type 2 diabetes, showed that moderate-severe OSA was associated with a greater
      risk of diabetes (RR 1.63; 95% confidence interval (CI): 1.09-2.45), as compared
      with the absence of OSA. Sensitivity analyses yielded similar results. For
      subjects with mild OSA, as compared with those without OSA, the pooled RR of
      developing type 2 diabetes was 1.22 (95% CI: 0.91-1.63). CONCLUSIONS: This meta
      analysis indicates that moderate-severe OSA is associated with an increased risk
      of type 2 diabetes, and this appears to be an independent risk factor for the
      development of diabetes.

PMID- 22988889
TI  - Differential effects of landscape-level environmental features on genetic
      structure in three codistributed tree species in Central America.
AB  - Landscape genetic studies use spatially explicit population genetic information
      to determine the physical and environmental causes of population genetic
      structure on regional scales. Comparative studies that identify common barriers
      to gene flow across multiple species within a community are important to both
      understand the evolutionary trajectories of populations and prioritize habitat
      conservation. Here, we use a comparative landscape genetic approach to ask
      whether gradients in temperature or precipitation seasonality structure genetic
      variation across three codistributed tree species in Central America, or whether
      a simpler (geographic distance) or more complex, species-specific environmental
      niche model is necessary to individually explain population genetic structure.
      Using descriptive statistics and causal modelling, we find that different factors
      best explain genetic distance in each of the three species: environmental niche
      distance in Bursera simaruba, geographic distance in Ficus insipida and
      historical barriers to gene flow or cryptic reproductive barriers for Brosimum
      alicastrum. This study confirms suggestions from previous studies of Central
      American tree species that imply that population genetic structure of trees in
      this region is determined by complex interactions of both historical and current
      barriers to gene flow.

PMID- 22988891
TI  - Preterm birth, ADHD and the ESSENCE in adult psychiatry.

PMID- 22988892
TI  - Synthesis and self-assembly of perylenetetracarboxylic diimide derivatives with
      helical oligo(L-lactic acid)n segments.
AB  - Three perylenetetracarboxylic diimide (PDI) derivatives consisting of a short
      oligo(L-lactic acid)(n) (O-LLA) segment at one imide nitrogen were synthesized.
      The polymers were characterized by (1)H NMR and gel permeation chromatography
      (GPC). Their properties were investigated by differential scanning calorimetry
      (DSC), X-ray diffraction (XRD) experiments, scanning electron microscopy (SEM),
      electronic absorption, and circular dichroism (CD) spectroscopy. The self
      assembly behavior of these PDIs in molten state as well as in solvent was
      examined. It was found that the structure and the morphology of the self-assembly
      of these polymers depend on the relative length of the O-LLA segment. The PDIs
      with longer O-LLA chains present liquid crystal properties with an obvious phase
      transition from disordered phase to an ordered (alpha) phase, which cannot be
      found for the PDIs with short O-LLA segments. The long O-LLA segments also caused
      a left-handed helicity for the aggregates of the PDIs from solution. This
      research demonstrated that one can control the order, aggregation mode, and
      morphology of the molecular aggregates by changing the length of the O-LLA
      chains. This information can be useful in the design of new organic materials
      that exhibit molecular aggregation.

PMID- 22988890
TI  - Immunomodulatory effect of water soluble extract separated from mycelium of
      Phellinus linteus on experimental atopic dermatitis.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is becoming a popular
      treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus)
      as one of the CAMs has been used to modulate cancers, inflammation and allergic
      activities. However, little evidence has been shown about its underlying
      mechanism of action by which it exerts a beneficial role in dermatological
      disease in vivo. In this study, we examined the immunomodulatory effects of P.
      linteus on experimental atopic dermatitis (AD) and elucidated its action
      mechanism. METHODS: The immunomodulatory effect of total extract of P. linteus on
      IgE production by human myeloma U266B1 cells was measured by ELISA. To further
      identify the effective components, P. linteus was fractionated into methanol
      soluble, water soluble and boiling water soluble extracts. Each extract was
      treated to U266B1 cells and primary B cells to compare their inhibitory effects
      on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis
      (AD) was established by alternative treatment of DNCB and house dust mite extract
      into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a
      positive control were topically applied to ears of atopic mouse every day for 2
      weeks and progression of the disease was estimated by the following criteria: (a)
      ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE
      level by ELSIA, (c) histological examination of ear tissue by H&E staining and
      (d) cytokine profile of total ear cells and CD4(+) T cells by real time PCR and
      ELSIA. RESULTS: Treatment of total extracts of P. linteus to U266B1 inhibited IgE
      secretion. Among the diverse extracts of P. linteus, water soluble extract of P.
      linteus (WA) significantly reduced the IgE production in primary B cells and B
      cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear
      swelling, erythema, and dryness and decreased recruitment of lymphocyte into the
      inflamed site. Interestingly WA treatment significantly reduced IgE level without
      affecting IgG levels and also down-regulated the levels of pathogenic cytokines
      (IL-4, IL-13, IL-12 and IFN-gamma) and chemokines (CCL17 and CCL22) involved in
      AD development. CONCLUSIONS: Our study indicates that protective effect of water
      soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE
      production and expression of AD associated pathogenic cytokines as well as
      chemokines, suggesting the beneficial effect of P. linteus to modulate allergic
      skin disease.

PMID- 22988893
TI  - Pathogen effects on vegetative and floral odours mediate vector attraction and
      host exposure in a complex pathosystem.
AB  - Pathogens can alter host phenotypes in ways that influence interactions between
      hosts and other organisms, including insect disease vectors. Such effects have
      implications for pathogen transmission, as well as host exposure to secondary
      pathogens, but are not well studied in natural systems, particularly for plant
      pathogens. Here, we report that the beetle-transmitted bacterial pathogen Erwinia
      tracheiphila - which causes a fatal wilt disease - alters the foliar and floral
      volatile emissions of its host (wild gourd, Cucurbita pepo ssp. texana) in ways
      that enhance both vector recruitment to infected plants and subsequent dispersal
      to healthy plants. Moreover, infection by Zucchini yellow mosaic virus (ZYMV),
      which also occurs at our study sites, reduces floral volatile emissions in a
      manner that discourages beetle recruitment and therefore likely reduces the
      exposure of virus-infected plants to the lethal bacterial pathogen - a finding
      consistent with our previous observation of dramatically reduced wilt disease
      incidence in ZYMV-infected plants.

PMID- 22988894
TI  - Thrombolysis for acute ischaemic stroke with alteplase in an Asian population:
      results of the multicenter, multinational Safe Implementation of Thrombolysis in
      Stroke-Non-European Union World (SITS-NEW).
AB  - BACKGROUND: Safe Implementation of Thrombolysis in Stroke-Non-European Union
      World was a multinational, prospective, open, monitored, observational study of
      intravenous alteplase as thrombolytic therapy in clinical practice. Safe
      Implementation of Thrombolysis in Stroke-Non-European Union World was required to
      assess the safety of alteplase in an Asian population by comparison with results
      from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study
      and pooled results from randomized controlled trials. AIMS AND/OR HYPOTHESIS: To
      evaluate the efficacy and safety of intravenous alteplase (0.9 mg/kg) as
      thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an
      Asian population. METHODS: The 591 patients included were treated at 48 centers
      in four countries (South Korea, China, India, and Singapore) between 2006 and
      2008. Primary outcomes were symptomatic (deterioration in National Institutes of
      Health Stroke Scale score >=4 or death within the first 24 h) intracerebral
      haemorrhage type 2 22-36 h after the thrombolysis and mortality at three-month
      follow-up. The secondary outcome was functional independence (modified Rankin
      Scale score 0-2) at three-months. Results were compared with those from Safe
      Implementation of Thrombolysis in Stroke-Monitoring Study (n = 6483) and pooled
      results of patients (n = 415) who received intravenous alteplase (0.9 mg/kg) zero
      to three-hours from onset of stroke symptoms in four randomized controlled
      trials (National Institute of Neurological Disorders and Stroke A and B,
      Altephase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke,
      and European Cooperative Acute Stroke Study II). RESULTS: Results are presented
      as Safe Implementation of Thrombolysis in Stroke-Non-European Union World vs.
      Safe Implementation of Thrombolysis in Stroke-Monitoring Study vs. pooled
      randomized controlled trials. Median age was 64 vs. 68 vs. 70 years, National
      Institutes of Health Stroke Scale score at baseline was 12 vs. 12 vs. 13, time
      from stroke onset to treatment was 130 vs. 140 vs. 135 mins, and females were
      36.4% vs. 39.8% vs. 41.2%. Main outcomes (proportion of patients and 95%
      confidence intervals) were symptomatic intracerebral haemorrhage: 1.9% (1.1-3.3)
      vs. 1.7% (1.4-2.0) vs. 3.1% (1.8-5.3); mortality: 10.2% (8.0-12.9) vs. 11.3%
      (10.5-12.1) vs. 16.4% (13.1-20.3); and functional independence: 62.5% (58.5-66.4)
      vs. 54.8% (53.5-56.0) vs. 50.1% (45.3-54.9) at three-months. Adjusted odds ratio
      (95% confidence intervals) between Safe Implementation of Thrombolysis in Stroke
      Non-European Union World and Safe Implementation of Thrombolysis in Stroke
      Monitoring Study, and between Safe Implementation of Thrombolysis in Stroke-Non
      European Union World and the pooled trials were 1.83 (0.89-3.77; P = 0.1156) and
      0.63 (0.19-2.07; P = 0.4470) for symptomatic intracerebral haemorrhage, 0.90
      (0.64-1.25; P = 0.5092) and 0.93 (0.52-1.64; P = 0.7915) for mortality at three
      months, and 1.57 (1.25-1.96; P < 0.0001) and 1.35 (0.91-2.00; P = 0.1325) for
      functional independence. CONCLUSIONS: These data demonstrate the safety and
      efficacy of the standard dose of intravenous alteplase (0.9 mg/kg) in an Asian
      population, as previously observed in the European population studied in Safe
      Implementation of Thrombolysis in Stroke-Monitoring Study and the populations in
      pooled randomized controlled trials, when used in routine clinical practice
      within three-hours of stroke onset. The findings should encourage wider use of
      thrombolytic therapy in Asian countries for suitable patients treated in stroke
      centers.

PMID- 22988895
TI  - Enhancing the production of Rhodobacter sphaeroides-derived physiologically
      active substances using carbonic anhydrase-immobilized electrospun nanofibers.
AB  - In order to achieve continuous biocatalytic hydration of CO(2), carbonic
      anhydrase (CA) derived from Rhodobacter sphaeroides was immobilized on
      electrospun polystyrene/poly(styrene-co-maleic anhydride) (PS/PSMA) nanofibers as
      cross-linked enzyme aggregates (CLEA). The CA-CLEA maintained more than 94.7% of
      its initial activity during 60 days of storage period at 4  degrees C and also
      retained more than 45.0% activity after 60 reuses. The capability of CA-CLEA to
      hydrolyze CO(2) was verified in terms of CaCO(3) precipitation. The immobilized
      CA induced enhanced cell growth of R. sphaeroides , which then increased the
      production of R. sphaeroides -derived organic substances including carotenoid,
      bacteriochlorophyll, porphyrin, and coenzyme Q10. Further exploitation of such
      nanofiber-catalyst complexes that allows environment friendly use of CO(2) is
      expected in a variety of research fields.

PMID- 22988896
TI  - Diversity of clinical manifestations and response to corticosteroids for
      idiopathic hypereosinophilic syndrome: retrospective study in 33 patients.
AB  - Idiopathic hypereosinophilic syndrome (IHES) is characterized by blood
      hypereosinophilia with no underlying cause and eosinophilia-associated organ
      dysfunction. Thirty-three patients, 20 female (61%) and 13 male (29%), with a
      median age of 56 years at diagnosis (range 16-77 years) were included in the
      study. The median blood eosinophilia at diagnosis was 7.6 * 10(9)/L and the
      median percentage of eosinophils in the bone marrow was 39.5%. The most common
      clinical manifestations were splenomegaly and cardiac involvement.
      Corticosteroids (CS) as monotherapy were initiated in all study patients. The
      median starting dose of prednisone was 30 mg daily (range 5-85 mg), and the
      maintenance dose varied from 5 mg twice weekly to 60 mg daily. Overall, 21
      patients (64%) responded to CS within a week. Seven patients (21%) were resistant
      or intolerant to CS. Five patients (15%) achieved a 50% reduction of blood
      eosinophilia. In conclusion, CS were found to be highly effective in IHES with
      manageable side effects.

PMID- 22988898
TI  - Transference interpretation in the treatment of borderline personality disorder
      patients.
AB  - Transference is seen as an important change mechanism in psychotherapeutic
      technique, although questions remain about its therapeutic use, especially with
      borderline personality disorder (BPD) patients. This article illustrates the
      lively debate about transference interpretation through the perspective of two
      psychotherapeutic techniques under empirical scrutiny--transference-focused
      psychotherapy (TFP) and mentalization-based treatment (MBT). Each technique
      offers a similar understanding and appreciation of transference, but they differ
      in their technical use of this change mechanism. The article presents a brief
      case study of a BPD patient. The treatment highlights the utility of each
      psychotherapeutic technique in understanding the developmental progress made by
      the patient in therapy. The authors argue that each technique may be useful in a
      long-term dynamic therapy, and that one can use an epigenetic framework to
      understand this observation.

PMID- 22988897
TI  - Women's experiences of factors that facilitate or inhibit gestational diabetes
      self-management.
AB  - BACKGROUND: Gestational diabetes rates have increased dramatically in the past
      two decades and this pattern of increase appears to relate primarily to the
      obesity epidemic, older maternal age and migration from world areas of high GDM
      risk. Women from disadvantaged and migrant backgrounds are most at risk of
      developing and of mismanaging this condition. The aim of the study was to explore
      the factors that facilitated or inhibited gestational diabetes self-management
      among women in a socially deprived area. METHODS: Fifteen pregnant women, with a
      diagnosis of gestational diabetes, were purposively recruited for this study.
      Qualitative semi structured interviews and 1 focus group were conducted when
      participants were approximately 28-38 weeks gestation. The study's theoretical
      framework was based on interpretative phenomenology and data was analysed using a
      thematic analysis approach. RESULTS: Women in this study identified a number of
      factors that complicated their task of GDM self-management. Barriers included:
      (1) time pressures; (2) physical constraints; (3) social constraints; (4) limited
      comprehension of requirements, and (5) insulin as an easier option. Factors
      facilitating GDM self-management included: thinking about the baby and
      psychological support from partners and families. CONCLUSION: Women from low
      socio economic and migrant backgrounds often struggle to comprehend GDM self
      management requirements. To improve adherence to management plans, these women
      require educational and supportive services that are culturally appropriate and
      aimed at a low level of literacy.

PMID- 22988899
TI  - Narcissism: its function in modulating self-conscious emotions.
AB  - This study focused on the functional aspects of narcissism in regulating self
      conscious emotions (guilt, shame, hubristic pride, and achievement-oriented
      pride) as well as two other attribution styles (externalization and detachment).
      The authors investigated Japanese university students (N = 452) with regard to
      their self-conscious emotions using the Test of Self-Conscious Affect-3 (TOSCA-3)
      and their narcissistic personality using the short version of Narcissistic
      Personality Inventory (NPI-S). Structural equation modeling was used for the
      analysis. The authors found that narcissism led individuals to feel achievement
      oriented pride, hubristic pride, externalization, and detachment, but inhibited
      feelings of shame. It did not have a significant effect on guilt. Shame-proneness
      prompted hubristic pride and externalization. Guilt-proneness inclined an
      individual toward achievement-oriented pride, but deterred externalization. In
      this article, the authors present and interpret these results in detail and then
      discuss how they can be utilized in psychotherapy.

PMID- 22988900
TI  - On not praying for the return of an amputated limb: conserving a relationship
      with God as the primary function of prayer.
AB  - Prayer is commonplace at times of illness. But what do people pray for? After
      reviewing recent work in the cognitive science of religion, the authors argue
      that pray-ers preferentially ask for psychological as opposed to physical
      outcomes because these are easier to accommodate God's intervention in the
      healing process. The authors exemplify this argument with recent studies of
      illness-related prayer. The findings from this study accord with other studies
      which demonstrate that those who follow spiritual pathways engage in efforts to
      conserve their understanding of and their relationship with the sacred. Thus, the
      authors argue that prayers to God are designed to enhance human health and well
      being in ways that conserve the sacred. Unanswered prayers in a health-related
      context then may elicit spiritual struggles and significant distress to patients.
      The authors conclude by discussing the implications of unanswered prayer and
      theodicy for psychotherapy, emphasizing the seminal work of Anna-Maria Rizzuto.

PMID- 22988901
TI  - Do attachment representations predict depression and anxiety in psychiatrically
      hospitalized prepubertal children?
AB  - Thirty-six prepubertal inpatients were videotaped completing five stories
      thematically related to attachment experiences and classified by their attachment
      representations. Children also completed the Children's Depression Inventory and
      Diagnostic Interview for Children and Adolescents-Revised. Mothers completed
      demographic questionnaires. Percentage of secure (B) attachment was only about
      one tenth of the normative percentage, anxious-ambivalent (C) attachment was
      between two and three times the normative percentage, and disorganized (D)
      attachment was almost twice the normative percentage. Both D attachment and the
      total number of disorganized story responses were associated with negative self
      esteem and clinical-range depression. Anxious-avoidant (A) attachment decreased
      the likelihood, while C and D attachment increased the likelihood, of separation
      anxiety disorder. Clinical intervention needs to focus on the meaning of parental
      relationships represented in the child's mind, specifically the negative self
      esteem and separation anxiety associated with the lack of felt security provided
      by the parents.

PMID- 22988903
TI  - Utility of epithelial membrane antigen immunostaining in the differentiation
      between palmoplantar pustulosis and pompholyx.

PMID- 22988904
TI  - Human blood RNA stabilization in samples collected and transported for a large
      biobank.
AB  - BACKGROUND: The Norwegian Mother and Child Cohort Study (MoBa) is a nation-wide
      population-based pregnancy cohort initiated in 1999, comprising more than 108.000
      pregnancies recruited between 1999 and 2008. In this study we evaluated the
      feasibility of integrating RNA analyses into existing MoBa protocols. We compared
      two different blood RNA collection tube systems - the PAXgeneTM Blood RNA system
      and the TempusTM Blood RNA system - and assessed the effects of suboptimal blood
      volumes in collection tubes and of transportation of blood samples by standard
      mail. Endpoints to characterize the samples were RNA quality and yield, and the
      RNA transcript stability of selected genes. FINDINGS: High-quality RNA could be
      extracted from blood samples stabilized with both PAXgene and Tempus tubes. The
      RNA yields obtained from the blood samples collected in Tempus tubes were
      consistently higher than from PAXgene tubes. Higher RNA yields were obtained from
      cord blood (3 - 4 times) compared to adult blood with both types of tubes.
      Transportation of samples by standard mail had moderate effects on RNA quality
      and RNA transcript stability; the overall RNA quality of the transported samples
      was high. Some unexplained changes in gene expression were noted, which seemed to
      correlate with suboptimal blood volumes collected in the tubes. Temperature
      variations during transportation may also be of some importance. CONCLUSIONS: Our
      results strongly suggest that special collection tubes are necessary for RNA
      stabilization and they should be used for establishing new biobanks. We also show
      that the 50,000 samples collected in the MoBa biobank provide RNA of high quality
      and in sufficient amounts to allow gene expression analyses for studying the
      association of disease with altered patterns of gene expression.

PMID- 22988905
TI  - Neurologic safety event rates in the SENTIS trial control population.
AB  - BACKGROUND: Adverse event (AE) rates for interventional stroke trials are not
      well established. AIMS: We prospectively evaluated control arm AEs from a
      randomized stroke trial to establish expected rates of neurologic AEs. METHODS:
      Control data from the Safety and Efficacy of NeuroFlo Technology in Ischemic
      Stroke (SENTIS) Trial were evaluated. Patients were >= 18 years with National
      Institutes of Health Stroke Scale (NIHSS) scores 5-18 within 14 h of stroke
      onset. Follow-up was 90 days. Neurological AEs and serious AEs (SAEs) were
      adjudicated and the following defined times used to determine treatment
      relatedness: 24-h imaging for intracranial hemorrhage (ICnH) including
      hemorrhagic transformation, 7 days each for cerebral edema and neurologic
      worsening/stroke progression, and 30 days for new ischemic strokes. RESULTS: The
      control group included 257 patients, 49.4% female, mean age of 68.3 years, and
      median NIHSS of 10. Neurologic AEs occurred at the following rates: ICnH 27.6%,
      cerebral edema 6.6%, neurologic worsening 18.3%, and new stroke 4.7%. Most of
      these events occurred within the defined times: ICnH 74.6%, cerebral edema 94.1%,
      neurologic worsening 87.2%, and new stroke 83.3%. CONCLUSIONS: SENTIS Trial
      control arm neurologic events provide estimates of expected AE rates and defined
      times that can be used for future stroke trial's safety assessments.

PMID- 22988906
TI  - Synthesis of tri- and tetrasubstituted pyrazoles via Ru(II) catalysis:
      intramolecular aerobic oxidative C-N coupling.
AB  - An unprecedented ruthenium(II)-catalyzed intramolecular oxidative C-N coupling
      method has been developed for the facile synthesis of a variety of synthetically
      challenging tri- and tetrasubstituted pyrazoles. Dioxygen gas is employed as the
      oxidant in this transformation. The reaction demonstrates excellent reactivity,
      functional group tolerance, and high yields.

PMID- 22988908
TI  - Modulation of tau protein fibrillization by oleocanthal.
AB  - Among the phenolic compounds extracted from extra virgin olive oil, oleocanthal
      (1) has attracted considerable attention in the modulation of many human
      diseases, such as inflammation and Alzheimer's disease (AD). Indeed, 1 is capable
      of altering the fibrillization of tau protein, which is one of the key factors at
      the basis of neurodegenerative diseases, and of covalently reacting with lysine
      epsilon-amino groups of the tau fragment K18 in an unspecific fashion. In the
      present study, an investigation of the recognition process and the reaction
      profile between 1 and the wild-type tau protein has been conducted by a circular
      dichroism, surface plasmon resonance, fluorescence, and mass spectrometry
      combined approach. As a result, 1 has been found to interact with tau-441,
      inducing stable conformational modifications of the protein secondary structure
      and also interfering with tau aggregation. These findings provide experimental
      support for the potential reduced risk of AD and related neurodegenerative
      diseases associated with olive oil consumption and may offer a new chemical
      scaffold for the development of AD-modulating agents.

PMID- 22988909
TI  - Comparison of representational spaces based on structural information in the
      development of QSAR models for benzylamino enaminone derivatives.
AB  - In this paper we study different representational spaces of molecule data sets
      based on 2D representation models for the building of QSAR models for the
      prediction of the activity of 37 benzylamino enaminone derivatives.
      Approximations based on classical similarity calculated from fingerprint
      representation of molecules and isomorphism obtained using sub-graph matching
      algorithms are compared to fragmentation-based approximations using partial least
      squares and genetic algorithms. The influence of the anchored position of a non
      common moiety and the kind of substituents in the common core structure of the
      data set are analysed, demonstrating the anomalous behaviour of some molecules
      and therefore the difficulty in building prediction models. These problems are
      solved by considering approximate similarity models. These models tune the
      prediction equations based on the size of the substituent and the anchored
      position, by adjusting the contribution of each substituent in similarity
      measurements calculated between the molecule data sets.

PMID- 22988907
TI  - Strong innate immune response and cell death in chicken splenocytes infected with
      genotype VIId Newcastle disease virus.
AB  - BACKGROUND: Genotype VIId Newcastle disease virus (NDV) isolates induce more
      severe damage to lymphoid tissues, especially to the spleen, when compared to
      virulent viruses of other genotypes. However, the biological basis of the unusual
      pathological changes remains largely unknown. METHODS: Virus replication,
      cytokine gene expression profile and cell death response in chicken splenocytes
      infected with two genotype VIId NDV strains (JS5/05 and JS3/05), genotype IX NDV
      strain F48E8 and genotype IV NDV strain Herts/33 were evaluated. Statistical
      significance of differences between experimental groups was determined using the
      Independent-Samples T test. RESULTS: JS5/05 and JS3/05 caused hyperinduction of
      type I interferons (IFNs) (IFN-alpha and -beta) during detection period compared
      to F48E8 and Herts/33. JS5/05 increased expression level of IFN-gamma gene at 6 h
      post-inoculation (pi) and JS3/05 initiated sustained activation of IFN-gamma
      within 24 h pi, whereas transcriptional levels of IFN-gamma remained unchanged at
      any of the time points during infection of F48E8 and Herts/33. In addition,
      compared to F48E8 and Herts/33, JS3/05 and JS5/05 significantly increased the
      amount of free nucleosomal DNA in splenocytes at 6 and 24 h pi respectively.
      Annexin-V and Proidium iodid (PI) double staining of infected cells showed that
      cell death induced by JS3/05 and JS5/05 was characterized by marked necrosis
      compared to F48E8 and Herts/33 at 24 h pi. These results indicate that genotype
      VIId NDV strains JS3/05 and JS5/05 elicited stronger innate immune and cell death
      responses in chicken splenocytes than F48E8 and Herts/33. JS5/05 replicated at a
      significantly higher efficiency in splenocytes than F48E8 and Herts/33. Early
      excessive cell death induced by JS3/05 infection partially impaired virus
      replication. CONCLUSIONS: Viral dysregulaiton of host response may be relevant to
      the severe pathological manifestation in the spleen following genotype VIId NDV
      infection.

PMID- 22988911
TI  - Laelapinae mites (Acari: Parasitiformes: Laelapidae) parasitic of sigmodontine
      rodents from northern Peru, with the description of a new species from Akodon
      aerosus (Rodentia: Cricetidae: Sigmodontinae).
AB  - Laelapine mites are common parasites of sigmodontine rodents in the Neotropics.
      However, few species are reported from Peru as a result of the low number of
      mammal surveys that include ectoparasite collections. Herein we report 12 species
      of mites from northern Peru. From these, 8 are reported for the first time for
      the country, and 1 is new to science , Androlaepaps aerosus sp. nov., the latter
      associated exclusively with the sigmodontine Akodon aerosus . Most of the
      laelapine species were host specific. The new species, included in the
      Androlaelaps rotundus species group, resembles An. rotundus "sensu stricto" and
      An. ulysespardinasi in general appearance but is unique in the length of the
      hypostomal seta h3 (>58 MUm), which is 3 times as long as the gnathosomal seta,
      and its tip reaching or over-reaching the gnathosomal setal bases; dorsal seta j2
      is very long (>70 MUm), almost reaching the point of j3.

PMID- 22988912
TI  - Alternative perspectives on the sustainability of Alaska's commercial fisheries.
AB  - Many believe commercial fisheries in Alaska (U.S.A.) are sustainability success
      stories, but ongoing socioeconomic problems across the state raise questions
      about how this sustainability is being defined and evaluated. Problems such as
      food insecurity and the disenfranchisement of Alaska Natives from fishing rights
      are well documented, yet these concerns are obscured by marketing campaigns that
      convey images of flourishing fishing communities and initiatives to certify
      Alaska's fisheries as responsibly managed. Fisheries management mandates and
      approaches built on such metrics and technologies as maximum sustainable yield
      and systems of tradable quotas actually serve to constrain, circumscribe, and
      marginalize some Alaskans' opportunities for effecting change in how the benefits
      of these fisheries are allocated. Beneath the narrative of sustainability, these
      management technologies perpetuate a cognitive ecological model of sustainability
      that is oriented to single-species outcomes, that casts people as parasites, and
      thus assumes the necessity of trade-offs between biological and social goals.
      Alternative cognitive models are available that draw metaphors from different
      ecological concepts such as keystone species and mutualisms. Such models, when
      used to inform management approaches, may improve societal outcomes in Alaska and
      elsewhere by promoting food security and sustainability through diversified
      natural resource harvest strategies that are more flexible and responsive to
      environmental variability and change.

PMID- 22988910
TI  - Prolonged FGF signaling is necessary for lung and liver induction in Xenopus.
AB  - BACKGROUND: FGF signaling plays numerous roles during organogenesis of the
      embryonic gut tube. Mouse explant studies suggest that different thresholds of
      FGF signaling from the cardiogenic mesoderm induce lung, liver, and pancreas
      lineages from the ventral foregut progenitor cells. The mechanisms that regulate
      FGF dose in vivo are unknown. Here we use Xenopus embryos to examine the
      hypothesis that a prolonged duration of FGF signaling from the mesoderm is
      required to induce foregut organs. RESULTS: We show that both mesoderm and FGF
      signaling are required for liver and lung development in Xenopus; formally
      demonstrating that this important step in organ induction is conserved with other
      vertebrate species. Prolonged contact with the mesoderm and persistent FGF
      signaling through both MEK and PI3K over an extended period of time are required
      for liver and lung specification. Inhibition of FGF signaling results in reduced
      liver and lung development, with a modest expansion of the pancreas/duodenum
      progenitor domain. Hyper-activation of FGF signaling has the opposite effect
      expanding liver and lung gene expression and repressing pancreatic markers. We
      show that FGF signaling is cell autonomously required in the endoderm and that a
      dominant negative FGF receptor decreases the ability of ventral foregut
      progenitor cells to contribute to the lung and liver buds. CONCLUSIONS: These
      results suggest that the liver and lungs are specified at progressively later
      times in development requiring mesoderm contact for different lengths of time.
      Our data suggest that this is achieved at least in part through prolonged FGF
      signaling. In addition to providing a foundation for further mechanistic studies
      on foregut organogenesis using the experimental advantages of the Xenopus system,
      these data have implications for the directed differentiation of stem cells into
      foregut lineages.

PMID- 22988913
TI  - Khat use among HIV voluntary counselling and testing centre clients in Ethiopia.
AB  - Khat (Catha edulis, a natural stimulant), has been used in Ethiopia for
      centuries. Over the past few decades, however, its use has dramatically
      increased, with recent research linking khat use to HIV status. Using qualitative
      methods, we explored the individual and micro-environmental characteristics of
      khat use and the social and physical contexts influencing type, acceptability and
      consequences of khat use. Among khat chewers attending an HIV voluntary
      counselling and testing centre in Addis Ababa, Ethiopia, we found that chewing
      typically starts at an early age (15-18 years). The majority of users are young
      (aged 18-35) and chew for pleasure, primarily in social settings. Over 25 types
      of khat, with varying effects were reported. Approximately half of the
      participants perceived khat to enhance sexual desire, while the rest claimed the
      effect on sexual desire to be the opposite. Alcohol use among chewers was high.
      Our findings suggest the need for culturally appropriate interventions that
      highlight the factors associated with khat use and the potential interplay
      between khat, alcohol and risky sexual behaviour.

PMID- 22988914
TI  - Optimal definition of inter-residual contact in globular proteins based on
      pairwise interaction energy calculations, its robustness, and applications.
AB  - Although a contact is an essential measurement for the topology as well as
      strength of non-covalent interactions in biomolecules and their complexes, there
      is no general agreement in the definition of this feature. Most of the
      definitions work with simple geometric criteria which do not fully reflect the
      energy content or ability of the biomolecular building blocks to arrange their
      environment. We offer a reasonable solution to this problem by distinguishing
      between "productive" and "non-productive" contacts based on their interaction
      energy strength and properties. We have proposed a method which converts the
      protein topology into a contact map that represents interactions with
      statistically significant high interaction energies. We do not prove that these
      contacts are exclusively stabilizing, but they represent a gateway to
      thermodynamically important rather than geometry-based contacts. The process is
      based on protein fragmentation and calculation of interaction energies using the
      OPLS force field and relies on pairwise additivity of amino acid interactions.
      Our approach integrates the treatment of different types of interactions,
      avoiding the problems resulting from different contributions to the overall
      stability and the different effect of the environment. The first applications on
      a set of homologous proteins have shown the usefulness of this classification for
      a sound estimate of protein stability.

PMID- 22988915
TI  - Perceived stress mediates the relationship between emotional loneliness and sleep
      quality over time in older adults.
AB  - OBJECTIVE: Both loneliness and poor sleep quality are common occurrences in late
      life and both are detrimental to physical and mental health. While loneliness may
      be difficult to intervene upon, there may be correlated factors, which, if
      alleviated, could mitigate the effects of loneliness and sleep quality on health
      in late life. DESIGN: A longitudinal, observational study whereby we gathered
      predictive variables at baseline and dependent variable (sleep) at follow-up.
      METHOD: We investigated the relationship between loneliness at baseline and sleep
      quality at follow-up in a group of 447 older adults attending the clinic for
      research participation. Loneliness, stress and sleep quality were all measured
      using self-report validated psychometric tools. RESULTS: We found that
      loneliness, specifically emotional loneliness, predicted sleep quality at follow
      up, controlling for demographic factors and for sleep quality at baseline. Upon
      applying mediation methods to the data, we then found that this relationship was
      mediated in part by perceived stress. CONCLUSION: We conclude that the impact of
      emotional loneliness on sleep quality in older adults is partly because of the
      stress experienced as a result of feeling lonely.

PMID- 22988916
TI  - Deep sequencing reveals extensive variation in the gut microbiota of wild
      mosquitoes from Kenya.
AB  - The mosquito midgut is a hostile environment that vector-borne parasites must
      survive to be transmitted. Commensal bacteria in the midgut can reduce the
      ability of mosquitoes to transmit disease, either by having direct anti-parasite
      effects or by stimulating basal immune responses of the insect host. As different
      bacteria have different effects on parasite development, the composition of the
      bacterial community in the mosquito gut is likely to affect the probability of
      disease transmission. We investigated the diversity of mosquito gut bacteria in
      the field using 454 pyrosequencing of 16S rRNA to build up a comprehensive
      picture of the diversity of gut bacteria in eight mosquito species in this
      population. We found that mosquito gut typically has a very simple gut microbiota
      that is dominated by a single bacterial taxon. Although different mosquito
      species share remarkably similar gut bacteria, individuals in a population are
      extremely variable and can have little overlap in the bacterial taxa present in
      their guts. This may be an important factor in causing differences in disease
      transmission rates within mosquito populations.

PMID- 22988917
TI  - Regression curves of brain metastases after gamma knife irradiation: Difference
      by tumor and patient characteristics.
AB  - Regression curves and local control rates of brain metastases after gamma knife
      treatment were evaluated to investigate differences in tumor response to
      radiation. A total of 203 metastases were serially evaluated using contrast
      enhanced MRI (or computed tomography) at 1, 2, 3, 4.5 and 6 months after a 20-Gy
      dose. Differences were evaluated in regression curves and control rates between
      tumors >=10 mm and tumors <10 mm in mean diameter, among three major histological
      subtypes of lung cancer, among adenocarcinomas of the lung, breast and
      colorectum, and between tumors in patients with above and below median hemoglobin
      levels. Smaller tumors shrank faster and yielded better control rates than larger
      tumors. Metastases from small cell and squamous cell carcinomas of the lung
      shrank faster than those from lung adenocarcinoma, but 6-month control rates were
      not different. Breast adenocarcinomas tended to shrink faster than lung
      adenocarcinomas, but the control rates were not different among adenocarcinomas
      of the lung, breast and colorectum. Tumors in patients with higher hemoglobin
      levels tended to shrink faster but the control rates were not different. Small
      cell and squamous cell carcinomas of the lung regress more rapidly than
      adenocarcinomas, although local control rates might not differ significantly.

PMID- 22988918
TI  - Geometric morphometrics of corolla shape: dissecting components of symmetric and
      asymmetric variation in Erysimum mediohispanicum (Brassicaceae).
AB  - Symmetry is an important feature of floral structure, and floral symmetries are
      diverse and often complex. We use a new morphometric approach for analysing
      shapes with complex types of symmetry, which partitions shape variation into a
      component of symmetric variation and different components of asymmetry. This
      approach, based on the mathematical theory of symmetry groups, can be used for
      landmark configurations with any type of symmetry and is therefore promising as a
      general framework for morphometric analyses of floral symmetry and asymmetry. We
      demonstrate this approach by quantifying floral shape variation in a wild
      population of Erysimum mediohispanicum (Brassicaceae). Flowers of this species
      are disymmetric, so that the symmetry in the left-right and adaxial-abaxial
      directions can be considered separately and in combination. Both principal
      component analysis and Procrustes ANOVA indicate that symmetric variation
      accounts for most of the total variance and that adaxial-abaxial asymmetry is the
      dominant component of fluctuating asymmetry. Each component is associated with
      specific patterns of shape variation. These results illustrate the potential of
      the new method and suggest new areas for future research. The new morphometric
      approach is promising for further analyses of floral symmetry and asymmetry in
      evolutionary and developmental contexts.

PMID- 22988919
TI  - Development of copper-catalyzed azide-alkyne cycloaddition for increased in vivo
      efficacy of interferon beta-1b by site-specific PEGylation.
AB  - The development of protein conjugate therapeutics requires control over the site
      of modification to allow for reproducible generation of a product with the
      desired potency, pharmacokinetic, and safety profile. Placement of a single
      nonnatural amino acid at the desired modification site of a recombinant protein,
      followed by a bioorthogonal reaction, can provide complete control. To this end,
      we describe the development of copper-catalyzed azide-alkyne cycloaddition
      (CuAAC, a click chemistry reaction) for site-specific PEGylation of interferon
      beta-1b (IFNb) containing azidohomoalanine (Aha) at the N-terminus. Reaction
      conditions were optimized using various propargyl-activated PEGs,
      tris(benzyltriazolylmethyl)amine (TBTA), copper sulfate, and dithiothreitol (DTT)
      in the presence of SDS. The requirement for air in order to advance the redox
      potential of the reaction was investigated. The addition of unreactive PEG diol
      reduced the required molar ratio to 2:1 PEG-alkyne to IFNb. The resultant method
      produced high conversion of Aha-containing IFNb to the single desired product.
      PEG-IFNbs with 10, 20, 30, and 40 kDa linear or 40 kDa branched PEGs were
      produced with these methods and compared. Increasing PEG size yielded decreasing
      in vitro antiviral activities along with concomitant increases in elimination
      half-life, AUC, and bioavailability when administered in rats or monkeys. A Daudi
      tumor xenograft model provided comparative evaluation of these combined effects,
      wherein a 40 kDa branched PEG-IFNb was much more effective than conjugates with
      smaller PEGs or unPEGylated IFNb at preventing tumor growth in spite of dosing
      with fewer units and lesser frequency. The results demonstrate the capability of
      site-specific nonnatural amino acid incorporation to generate novel biomolecule
      conjugates with increased in vivo efficacy.

PMID- 22988920
TI  - Home medication management practices and associated factors among patients with
      selected chronic diseases in a community pharmacy in Uganda.
AB  - BACKGROUND: Chronic diseases are rapidly increasing and are currently the major
      cause of death and disability worldwide. Patients with chronic diseases
      experience many challenges including medicine-related problems. However, there is
      limited information about the home management of medicines among these patients.
      This study therefore was to determine home medication management practices and
      associated factors among patients with chronic diseases seeking care in a
      community pharmacy in Uganda. METHODS: A cross-sectional study was conducted in a
      community pharmacy in Kampala from June to July 2010. A total of 207 consenting
      chronic disease patients or caregivers of children with chronic disease were
      consecutively sampled. The patients were visited at home to evaluate their drug
      management practices and to check their medical forms for disease types and drugs
      prescribed. An interviewer-administered questionnaire and an observation
      checklist were used to collect the data. RESULTS: Overall home medication
      management was inappropriate for 70% (n = 145) of the participants (95% CI = 63.3
      76.2) and was associated with perceived severity of disease (not severe OR =0.40,
      moderately severe OR = 0.35), duration of disease >5 years (OR = 2.15), and
      health worker not assessing for response to treatment (OR = 2.53). About 52% (n =
      107) had inappropriate storage which was associated with inadequate information
      about the disease (OR = 2.39) and distance to the health facility >5 kilometres
      (OR = 2.82). Fifteen percent (n = 31) had no drug administration schedule and
      this was associated with increasing age (OR = 0.97), inadequate information about
      the disease (OR = 2.96), and missing last appointment for medical review (OR =
      6.55). About 9% (n = 18) had actual medication duplication; 1.4% (n = 3) had
      expired medicines; while 18.4% (n = 38) had drug hoarding associated with
      increasing number of prescribers (OR = 1.34) and duration of disease (OR = 2.06).
      About 51% (n = 105) had multiple prescribers associated with perceiving the
      disease to be non severe (OR = 0.27), and having more than one chronic disease
      (OR = 2.37). CONCLUSIONS: Patients with chronic disease have poor home management
      of medicines. In order to limit the occurrence of poor outcomes of treatment or
      drug toxicity, health providers need to strengthen the education of patients with
      chronic disease on how to handle their medicines at home.

PMID- 22988921
TI  - Self-assembly in the mixtures of surfactant and dye molecule controlled via
      temperature and beta-cyclodextrin recognition.
AB  - A new ternary system of tetradecyldimethylamine oxide (C(14)DMAO)/4-phenylazo
      benzoic acid (AzoH)/H(2)O was first investigated, and it was found that the self
      assembly can be regulated via temperature and beta-cyclodextrin (beta-CD)
      recognition. In the temperature regulated self-assembly, the self-assembled phase
      structural transition between wormlike micelles and multilamellar vesicles
      (onions) were determined by cryogenic-transmission electron microscopy (cryo-TEM)
      images and (2)H nuclear magnetic resonance ((2)H NMR) spectra. The phase
      structural transition temperatures (PSTT) controlled by changing the amount of
      AzoH were measured by differential scanning calorimetry analysis. The self
      assembled phase structural transition mechanism was discussed. It is argued that
      the self-assembled phase structural transition is the synergetic balance among
      the hydrophilic headgroup, steric structures of the hydrophobic chain, and
      membrane charge. beta-CD molecules were used as controlling hands to modulate the
      phase structural transition of self-assembly of the C(14)DMAO/AzoH/H(2)O system
      in solution via snatching C(14)DMAO molecules. The phase structural transitions
      from the threadlike micellar phase to the lamellar phase and from the lamellar
      phase to the vesicular phase can each be controlled because of the beta-CD
      molecular recognition. The phase structural transitions were confirmed by cryo
      TEM observations and (2)H NMR measurements. The rheological properties were also
      investigated to display the importance in the phase structural transition. It was
      found that the dye molecule, AzoH, is harder to enclose by beta-CD than by
      C(14)DMAO because of the lower complex stability constant (i.e., K(C(14)DMAO@beta
      CD) ? K(AzoH@beta-CD). Therefore, the phase structural transition is mainly
      controlled by the inclusion of C(14)DMAO into the hydrophobic cavity of beta-CD
      molecules. The phase structural transition controlled via temperature and beta-CD
      may find potential applications such as in actuators, shape memories, drug
      delivery systems, and drag-reducing fluids, etc.

PMID- 22988922
TI  - Quantitative proteomic approaches in biomarker discovery of inflammatory bowel
      disease.
AB  - Proteomics offers considerable opportunities for either enhancing our biological
      understanding or discovering biomarkers, blood and biopsied specimen-based
      proteomic approaches, provide reproducible and quantitative tools that can
      complement clinical assessments and aid clinicians in the diagnosis and treatment
      of inflammatory bowel disease (IBD). Sometimes a differential diagnosis of
      Crohn's disease (CD) and ulcerative colitis (UC) and the prediction of treatment
      response can be deduced by finding meaningful biomarkers, for which the central
      platform for proteomics is tandem mass spectrometry (MS/MS). A range of workflows
      are available for protein (or peptide) separation prior to MS/MS as well as
      bioinformatics analysis to achieve protein identification, for which two
      dimensional electrophoresis (2-DE) and subsequent mass spectrometry (MS), liquid
      chromatography-MS, difference gel electrophoresis following 2-DE, isobaric tags
      for relative and absolute quantification (iTRAQ), stable isotope labeling by
      amino acids and label-free quantification are under development. In this article,
      the current status and perspective of these advanced proteomic technologies are
      introduced, with examples of recent biomarkers focused on the diagnosis,
      treatment response, prognosis of IBD, and even colitis-associated carcinogenesis
      in both animal models and human patients.

PMID- 22988923
TI  - Characteristics of achalasia subtypes in untreated Chinese patients: a high
      resolution manometry study.
AB  - OBJECTIVE: To evaluate and compare the clinical characteristics, manometric
      results and treatment outcomes of different subtypes of achalasia in untreated
      Chinese patients using high-resolution esophageal manometry. METHODS: A total of
      75 achalasia patients and 34 healthy controls were enrolled in the study, and
      three achalasia subtypes were determined based on the Chicago classification.
      Clinical characteristics, manometric and treatment outcomes were compared.
      RESULTS: In all, 25 patients were classified as type I, 46 as type II and 4 as
      type III. The mean overall length of lower esophageal sphincter (LES) in type III
      was significantly longer than those in the controls and type I patients (P <
      0.05), and abdominal LES length was significantly longer in type III than those
      in controls, type I and type II patients. All subtypes of achalasia had higher
      resting and residual LES pressures than those found in healthy controls (P <
      0.05). Resting upper esophageal sphincter (UES) pressure in type III patients was
      significantly lower than those in healthy controls and type I patients, whereas
      types I and II patients had higher residual UES pressures compared with healthy
      controls (P < 0.05). Type II patients had a better response to the treatment than
      type I and III patients. CONCLUSIONS: Type II is more common in untreated Chinese
      achalasia patients, and type II patients had better treatment outcomes than other
      types of patients. Large-sample multicenter trials are necessary in the future.

PMID- 22988924
TI  - Change of mucosal color in early gastric cancer.
AB  - OBJECTIVE: To investigate the association between mucosal color change and the
      characteristics of early gastric cancer (EGC). METHODS: Data of consecutive
      patients with EGC resected between August 2005 and October 2010 at Konkuk
      University Medical Center were analyzed retrospectively. The characteristics of
      EGC relative to mucosal color change were analyzed. RESULTS: Whitish
      discoloration of the cancer was linked to female to male gender ratio (P =
      0.009), large tumor size (P < 0.001), deep invasion (P = 0.046) and depressed
      contours (P < 0.001) compared with EGC without discoloration or with hyperemic
      change. In addition, a whitish discoloration was also related to signet ring cell
      carcinoma (P < 0.001) and diffuse type carcinoma based on Lauren's classification
      (P < 0.001). On multiple linear regression analysis, diffuse type based on
      Lauren's classification (P = 0.017) and depth of invasion (P = 0.003) were
      significant independent factors for whitish discoloration. CONCLUSIONS: Mucosal
      color change is an important clue in the diagnosis of EGC. EGC with whitish
      discoloration needs more attention due to its link with the diffuse type of
      Lauren's classification.

PMID- 22988925
TI  - Factors influencing diagnosis of colorectal cancer: a hospital-based survey in
      China.
AB  - OBJECTIVE: To investigate the diagnostic status of colorectal cancer (CRC) and
      the influence of early diagnosis and cancer stage in a tertiary care hospital in
      China. METHODS: Face-to-face interviews were conducted in 364 consecutive CRC
      patients who had never participated in CRC screening. Initial symptoms, diagnosis
      and treatment delay were determined using a questionnaire. Factors influencing
      diagnostic status were analyzed using univariate analysis and logistic regression
      model. RESULTS: A total of 307 patients were enrolled, in which 128 were with
      colon cancer and 179 with rectal cancer. The duration of diagnosis delay was
      significant longer than that of treatment delay. Unlike rectal cancer, colon
      cancer was likely to be treated at an advanced stage with a short interval
      between symptom onset and treatment. Colon cancer patients with a history of
      biliary tract or gallbladder stones, aged >= 50 years and with abdominal mass or
      intestinal obstruction as the initial symptom were diagnosed and treated much
      earlier. In rectal cancer, women and non-smokers were diagnosed and treated
      quickly. Factors correlated with early cancer stage were found in colon cancer,
      including bloody stool as the initial symptom (OR = 2.63, 95% CI 1.08-6.25, P =
      0.034) and a history of appendectomy (OR = 4.00, 95% CI 1.15-14.29, P = 0.029).
      CONCLUSIONS: The factors contributing to early cancer detection were identified
      but their clinical value is limited. Diagnosis by symptoms suggesting CRC needs
      to be improved and CRC screening should be vigorously promoted.

PMID- 22988926
TI  - Inhibitory effect of Ginkgo biloba extract on fatty liver: regulation of
      carnitine palmitoyltransferase 1a and fatty acid metabolism.
AB  - OBJECTIVE: To investigate the potential effect of Ginkgo biloba extract (GBE) on
      the prevention and treatment of nonalcoholic fatty liver disease (NAFLD).
      METHODS: Male Wistar rats were divided into 4 groups (the control group, GBE
      group, high-fat diet [HFD] group and HFD + GBE group). The human hepatocellular
      carcinoma cell line (HepG2) was treated with GBE and its flavonoid ingredients.
      The fatty acid composition of the rat liver was analyzed with gas
      chromatography/time-of-flight mass spectrometry (GC/TOFMS). Triglyceride contents
      of both the rat liver and HepG2 cells were measured by enzymatic colorimetric
      method. The expressions of fatty acid metabolism-related genes were analyzed with
      real-time reverse transcription-polymerase chain reaction (RT-PCR). The protein
      expression and enzymatic activity were subsequently measured. RESULTS: In rat
      livers, GBE reduced the elevations of hepatic triglyceride contents caused by HFD
      and the increased hepatic fatty acids were differentially affected by GBE.
      Notably, the expression and total activity of the fatty acid beta-oxidation rate
      limiting enzyme, carnitine palmitoyltransferase 1a (CPT1A), were also promoted
      with GBE ingestion. In HepG2 cells, GBE and its ingredients, quercetin,
      kaempferol and isorhamnetin, could decrease the cellular triglyceride content and
      upregulate the expression and total activity of CPT1A, respectively. CONCLUSIONS:
      The triglyceride-lowering effect of GBE on the HFD rat liver is closely
      associated with the increased expression and activity of CPT1A, and the flavonoid
      ingredients are the major contributors of GBE.

PMID- 22988927
TI  - Role of nicotine in gallbladder carcinoma: a preliminary report.
AB  - OBJECTIVE: To assess the role of nicotine in gallbladder carcinoma and its
      association with the stage and degree of cancer differentiation. METHODS: Tissue
      samples from gallbladder were obtained from 20 patients with gallbladder cancer
      and 20 age- and gender-matched patients with cholelithiasis who served as the
      control group. Gallbladder tissue (2 g) was extracted and analyzed for nicotine
      content using capillary gas chromatography. Nitrogen was used as the carrier gas.
      Standard curves of nicotine in methanol were made by injecting the internal
      standards. RESULTS: A significantly higher tissue nicotine concentration was
      observed in the gallbladder carcinoma group than that in the control group
      (179.63 ng/mg vs 6.00 ng/mg, P < 0.001). The stage and degree of cancer
      differentiation did not seem to affect the nicotine levels. Gallbladder tissue
      contained a significantly higher nicotine concentration in smokers with cancer
      compared with those in the control group (1570.00 ng/mg vs 232.25 ng/mg, P <
      0.001). Interestingly, non-smokers in cancer group also had a higher nicotine
      concentration than the control group (161.50 ng/mg vs 4.00 ng/mg, P = 0.002).
      CONCLUSION: Nicotine is selectively concentrated in malignant gallbladder tissue
      irrespective of smoking status, showing its strong association with gallbladder
      cancer.

PMID- 22988928
TI  - Simultaneous resection of abdominal cancer and synchronous pancreaticoduodenal
      metastasis: indications and literature review.
AB  - OBJECTIVE: This study was aimed to identify the potential indications for
      simultaneous resection of abdominal cancer and synchronous pancreaticoduodenal
      metastasis (SRAPM) and improve the efficacy of SRAPM. METHODS: The data of 34
      patients who underwent SRAPM were retrospectively reviewed. The intraoperative
      findings, morbidity and mortality, patterns of tumor invasion in the pancreas and
      duodenum, lymph node metastases, long-term outcomes and causes of death were
      evaluated. RESULTS: Fourteen patients (41.2%) developed complications, and 2 died
      of pancreatic fistulas with abdominal bleeding. The in-hospital mortality was
      5.9%. The overall 1-year, 2-year and 3-year survival rates were 52.9%, 32.3% and
      21.8%, respectively. The survival rates depended on the primary tumor, the
      invasion pattern, the presence of metastatic lymph nodes at the paraaortic site
      and the presence of residual tumor. The follow-up outcomes revealed that the main
      causes of death were as follows: systemic metastasis (n = 7), peritoneal
      metastasis (n = 6) and intrahepatic metastasis (n = 6). CONCLUSIONS: SRAPM is
      indicated for low-grade malignant tumors and in cases with direct invasion of the
      pancreaticoduodenum. The presence of metastatic lymph nodes at the paraaortic
      site, intrahepatic metastasis, micro-peritoneal metastasis, and distinct
      metastasis should be contraindications for the surgical procedure.

PMID- 22988929
TI  - Splenic arteriovenous fistula: unusual cause of portal hypertension complicated
      with gastric variceal bleeding.

PMID- 22988931
TI  - Employment of a new tripodal ligand for the synthesis of cobalt(II/III),
      nickel(II), and copper(II) clusters: magnetic, optical, and thermal properties.
AB  - The employment of 2-(beta-naphthalideneamino)-2-(hydroxymethyl)-1-propanol
      (LH(3)) in cobalt, nickel, and copper chemistry has led to the isolation of five
      new metallic complexes with interesting magnetic properties. More specifically,
      the reaction of Co(OAc)(2).4H(2)O with LH(3) in MeOH in the presence of NEt(3)
      under solvothermal conditions forms the complex
      [Co(III)(2)Co(II)(3)(L)(2)(LH)(2)(L')(OAc)].8.5MeOH (1.8.5MeOH; L' = monoanion of
      2-hydroxy-1-naphthaldehyde), while in nickel chemistry, a similar reaction of
      Ni(OAc)(2).6H(2)O with LH(3) in MeCN in the presence of NEt(3) under high
      pressure/temperature forms the complex [Ni(II)(LH(2))(2)].2MeCN (2.2MeCN).
      Repeating the same reaction in MeOH and switching from Ni(OAc)(2).4H(2)O to
      NiSO(4).4H(2)O produces the complex
      [Ni(II)(4)(HL)(3)(OMe)(MeOH)(3)](SO(4))(0.5).2MeOH (3.2MeOH) under solvothermal
      conditions. Furthermore, in copper chemistry, the reaction of
      Cu(2)(OAc)(4).2H(2)O with LH(3) in the presence of NEt(3) in MeOH under
      solvothermal conditions affords the complex [Cu(II)(4)(LH)(4)] (4), while the
      same reaction under ambient temperature and pressure conditions forms
      [Cu(II)(4)(LH)(4)] .3.5MeOH.2.25H(2)O (5.3.5MeOH.2.25H(2)O). Complex 1 is a mixed
      valent [Co(III)(2)Co(II)(3)] complex, consisting of three edge-sharing [Co(3)]
      triangles. Complex 2 is a nickel(II) monomer in which the central metal is found
      in an octahedral geometry, while complex 3 describes a [Ni(II)(4)] cubane.
      Complexes 4 and 5 may be considered as structural isomers because they possess
      the same formulas but different topologies: 4 describes a highly distorted
      [Cu(II)(4)(OR)(4)](4+) eight-membered ring, while 5 consists of a distorted
      [Cu(II)(4)(MU(3)-OR)(4)](4+) cubane. In addition, 5 can be converted to 4 in
      excellent yield under solvothermal conditions. Direct-current magnetic
      susceptibility studies have been carried out in the 5-300 K range for complexes 1
      and 3-5, revealing the possibility of a high-spin ground state for 1, an S = 4
      ground state for 2, and diamagnetic ground states for 4 and 5.

PMID- 22988930
TI  - Chronic alcohol-induced hepatic insulin resistance and endoplasmic reticulum
      stress ameliorated by peroxisome-proliferator activated receptor-delta agonist
      treatment.
AB  - BACKGROUND AND AIM: Chronic alcoholic liver disease is associated with hepatic
      insulin resistance, dysregulated lipid metabolism with increased toxic lipid
      (ceramide) accumulation, lipid peroxidation, and oxidative and endoplasmic
      reticulum (ER) stress. Peroxisome-proliferator activated receptor (PPAR) agonists
      are insulin sensitizers that can restore hepatic insulin responsiveness in both
      alcohol and non-alcohol-related steatohepatitis. Herein, we demonstrate that
      treatment with a PPAR-delta agonist enhances insulin signaling and reduces the
      severities of ER stress and ceramide accumulation in an experimental model of
      ethanol-induced steatohepatitis. METHODS: Adult male Long Evans rats were pair
      fed with isocaloric liquid diets containing 0% or 37% ethanol (caloric) for 8
      weeks. After 3 weeks on the diets, rats were treated with vehicle or PPAR-delta
      agonist twice weekly by i.p. injection. RESULTS: Ethanol-fed rats developed
      steatohepatitis with inhibition of signaling through the insulin and insulin-like
      growth factor-1 receptors, and Akt activated pathways. Despite continued ethanol
      exposure, PPAR-delta agonist co-treatments increased Akt activation, reduced
      multiple molecular indices of ER stress and steatohepatitis. CONCLUSIONS: These
      results suggest that PPAR-delta agonist rescue of chronic alcoholic liver disease
      is mediated by enhancement of insulin signaling through Akt/metabolic pathways
      that reduce lipotoxicity and ER stress.

PMID- 22988932
TI  - Modified release terbutaline (SKP1052) for hypoglycaemia prevention: a proof-of
      concept study in people with type 1 diabetes mellitus.
AB  - AIMS: In this randomized, single blind, cross-over study 2.5 mg and 5 mg of the
      modified-release terbutaline formulation (SKP-1052) were compared with
      conventional immediate-release terbutaline (IRT, 5 mg) and placebo on overnight
      blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes
      mellitus. METHODS: Subjects received subcutaneous injections of insulin glargine
      (individualized doses) before dinner. SKP-1052, IRT or placebo was administered
      around 21:00 hours. BG and terbutaline concentrations were monitored overnight
      for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0-10 h, primary
      endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia
      rates as well as pharmacokinetic (PK) endpoints. RESULTS: SKP-1052 delayed
      release of terbutaline by 2 h [PK-tmax (mean +/- SD) 5.0 +/- 2.1 h (2.5 mg) and
      4.7 +/- 1.7 h (5 mg) vs. 2.6 +/- 1.3 h with IRT, p < 0.01, respectively].
      Compared with placebo, no significant differences were observed for BGn 0-10 h
      across treatments, but both 5 mg formulations showed less hypoglycaemic events
      [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95 mg/dl) and
      BGmorning (126, 126 and 101 mg/dl, all comparisons p < 0.05 vs. placebo).
      Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5
      mg SKP-1052 vs. placebo. CONCLUSIONS: Compared with IRT SKP-1052 delays release
      of terbutaline. 2.5 mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose
      without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting
      hyperglycaemia vs. placebo. Future studies will investigate optimized doses of
      SKP-1052 for nocturnal hypoglycaemia prevention.

PMID- 22988933
TI  - A new modified prophylactic scheme against liposomal cytarabine-induced
      arachnoiditis in adult patients with lymphoma.

PMID- 22988935
TI  - Use of fully biodegradable panels to reduce derelict pot threats to marine fauna.
AB  - Fishing pots (i.e., traps) are designed to catch fish or crustaceans and are used
      globally. Lost pots are a concern for a variety of fisheries, and there are
      reports that 10-70% of deployed pots are lost annually. Derelict fishing pots can
      be a source of mortality for target and bycatch species for several years.
      Because continual removal of derelict gear can be impractical over large spatial
      extents, modifications are needed to disarm gear once it is lost. We tested a
      fully biodegradable panel with a cull or escape ring designed for placement on
      the sides of a crab pot that completely degrades into environmentally neutral
      constituents after approximately 1 year. This panel is relatively inexpensive,
      easy to install, and can be used in multiple fisheries. We used the blue crab
      (Callinectes sapidus) fishery as a test case because it is a large pot fishery
      and blue crab pots are similar to traps used in other pot fisheries. We had
      commercial fishers deploy pots with panels alongside standard pots in Chesapeake
      Bay (U.S.A.) to assess potential effects of our experimental pots on blue crab
      catch. We compared the number, biomass, and size of crabs captured between
      standard and experimental pots and evaluated differences in catch over a crabbing
      season (March-November) at five locations. There was no evidence that
      biodegradable panels adversely affected catch. In all locations and time periods,
      legal catches were comparable in abundance, biomass, and size between
      experimental and standard pots. Properly designed biodegradable panels appear to
      be a viable solution to mitigate adverse effects of derelict pots.

PMID- 22988934
TI  - Yoga for breast cancer patients and survivors: a systematic review and meta
      analysis.
AB  - BACKGROUND: Many breast cancer patients and survivors use yoga to cope with their
      disease. The aim of this review was to systematically assess and meta-analyze the
      evidence for effects of yoga on health-related quality of life and psychological
      health in breast cancer patients and survivors. METHODS: MEDLINE, PsycInfo,
      EMBASE, CAMBASE, and the Cochrane Library were screened through February 2012.
      Randomized controlled trials (RCTs) comparing yoga to controls were analyzed when
      they assessed health-related quality of life or psychological health in breast
      cancer patients or survivors. Risk of bias was assessed using the Cochrane risk
      of bias tool. Standardized mean differences (SMD) and 95% confidence intervals
      (CI) were calculated. RESULTS: Twelve RCTs with a total of 742 participants were
      included. Seven RCTs compared yoga to no treatment; 3 RCTs compared yoga to
      supportive therapy; 1 RCT compared yoga to health education; and 1 RCT compared a
      combination of physiotherapy and yoga to physiotherapy alone. Evidence was found
      for short-term effects on global health-related quality of life (SMD = 0.62 [95%
      CI: 0.04 to 1.21]; P = 0.04), functional (SMD = 0.30 [95% CI: 0.03 to 0.57),
      social (SMD = 0.29 [95% CI: 0.08 to 0.50]; P < 0.01), and spiritual well-being
      (SMD = 0.41 [95% CI: 0.08; 0.74]; P = 0.01). These effects were, however, only
      present in studies with unclear or high risk of selection bias. Short-term
      effects on psychological health also were found: anxiety (SMD = -1.51 [95% CI: 
      2.47; -0.55]; P < 0.01), depression (SMD = -1.59 [95% CI: -2.68 to -0.51]; P <
      0.01), perceived stress (SMD = -1.14 [95% CI:-2.16; -0.12]; P = 0.03), and
      psychological distress (SMD = -0.86 [95% CI:-1.50; -0.22]; P < 0.01). Subgroup
      analyses revealed evidence of efficacy only for yoga during active cancer
      treatment but not after completion of active treatment. CONCLUSIONS: This
      systematic review found evidence for short-term effects of yoga in improving
      psychological health in breast cancer patients. The short-term effects on health
      related quality of life could not be clearly distinguished from bias. Yoga can be
      recommended as an intervention to improve psychological health during breast
      cancer treatment.

PMID- 22988936
TI  - Callosal atrophy in multiple sclerosis is related to cognitive speed.
AB  - BACKGROUND: Long-term changes regarding corpus callosum area (CCA) and
      information processing speed in cognitive and sensory-motor tasks have rarely
      been studied in multiple sclerosis (MS). OBJECTIVE AND METHODS: Information
      processing speed in cognitive (Symbol Digit Modalities Test, SDMT), sensory
      (visual and auditory reaction time) and motor (finger-tapping speed, FT; right
      and left hand) tasks as well as auditory inter-hemispheric transfer (verbal
      dichotic listening, VDL) was related to CCA, measured by MRI at baseline and at
      follow-up after nine years in 22 patients with MS. Possible confounding by
      demographic (age, gender and education), clinical (symptom onset, duration,
      severity of disease) and relative brain volume (RBV) as well as T2 lesion load
      was taken into account. RESULTS: The smaller the CCA at baseline, the slower was
      SDMT performance at baseline. In a similar way, CCA at follow-up was associated
      with poor SDMT result at follow-up. Furthermore, the higher the annual rate of
      change in CCA, the poorer was performance in VDL on the left ear and the more
      pronounced was the right ear advantage. A positive relationship between
      performance in VDL right ear and annual rate of change in RBV was also seen.
      Sensory-motor tests were not significantly associated with CCA. T2 lesion load at
      baseline was associated with FT performance at baseline. Demographic, clinical
      and radiological (RBV and T2 lesion load) characteristics did not confound the
      significant relation between CCA and SDMT. CONCLUSIONS: CCA unlike RBV and T2
      lesion load was associated with SDMT, which indicated a marked cognitive rather
      than perceptual-motor component.

PMID- 22988937
TI  - Discovery of tetrasubstituted pyrazines as semiochemicals in a sexually deceptive
      orchid.
AB  - Sexually deceptive orchids employ mimicry of insect sex pheromones to exploit a
      diverse group of pollinators. The chemical structures of five semiochemicals (1
      3, 7, 8) produced by populations of the warty hammer orchid, Drakaea livida,
      pollinated by a thynnine wasp in the genus Catocheilus were elucidated. With the
      exception of (2,5-dimethylpyrazin-3-yl)methyl 3-methylbutanoate (7), all active
      compounds were tetrasubstituted pyrazines, including hydroxymethyl (1) and ester
      (2 and 3) trimethylpyrazine derivatives. Male Catocheilus wasps were responsive
      to all of these compounds in GC-EAD experiments.

PMID- 22988938
TI  - The polyomaviruses WUPyV and KIPyV: a retrospective quantitative analysis in
      patients undergoing hematopoietic stem cell transplantation.
AB  - BACKGROUND: The polyomaviruses WUPyV and KIPyV have been detected in various
      sample types including feces indicating pathogenicity in the gastrointestinal
      (GI) system. However, quantitative viral load data from other simultaneously
      collected sample types are missing. As a consequence, primary replication in the
      GI system cannot be differentiated from swallowed virus from the respiratory
      tract. Here we present a retrospective quantitative longitudinal analysis in
      simultaneously harvested specimens from different organ sites of patients
      undergoing hematopoietic stem cell transplantation (HSCT). This allows the
      definition of sample types where deoxyribonucleic acid (DNA) detection can be
      expected and, as a consequence, the identification of their primary replication
      site. FINDINGS: Viral DNA loads from 37 patients undergoing HSCT were quantified
      in respiratory tract secretions (RTS), stool and urine samples as well as in
      leukocytes (n = 449). Leukocyte-associated virus could not be found. WUPyV was
      found in feces, RTS and urine samples of an infant, while KIPyV was repeatedly
      detected in RTS and stool samples of 4 adult patients.RTS and stool samples were
      matched to determine the viral load difference showing a mean difference of 2.3
      log copies/ml (p < 0.001). CONCLUSIONS: The data collected in this study suggest
      that virus detection in the GI tract results from swallowed virus from the
      respiratory tract (RT). We conclude that shedding from the RT should be ruled out
      before viral DNA detection in the feces can be correlated to GI symptoms.

PMID- 22988939
TI  - Parallel lipoplex folding pathways revealed using magnetic tweezers.
AB  - Lipid-coated DNA nanoparticles (lipoplexes) are a powerful gene delivery tool
      with promising therapeutic applications. The mechanism of lipoplex assembly
      remains poorly understood. We explored DNA packing by a cationic lipid DSTAP
      (distearoyl trimethylammonium-propane) using magnetic tweezers. DSTAP-induced DNA
      condensation occurred as a series of bursts with the mean step size of 60-80 nm.
      The pause time preceding the steps could be approximated as a bimodal
      distribution, which reveals at least two distinct condensation pathways. The
      rapidly condensed DNA was more resilient to force-induced decondensation. The
      proportion of the stable, fast-formed complexes decreased at high salt
      concentrations. A similar trend was observed in bulk experiments. Lipoplexes
      assembled at low salt concentration more efficiently shielded DNA from
      fluorescent dyes and DNase even after transfer to the high salt conditions. These
      data reveal that lipoplex folding occurs via two parallel pathways even at the
      single molecule level. The progress through the two pathways can be monitored in
      real time using single DNA manipulations. The relative efficiency of the two
      pathways can be varied by external conditions.

PMID- 22988940
TI  - A tale of two chitons: is habitat specialisation linked to distinct associated
      bacterial communities?
AB  - Although most chitons (Mollusca: Polyplacophora) are shallow-water molluscs,
      diverse species also occur in deep-sea habitats. We investigated the feeding
      strategies of two species, Leptochiton boucheti and Nierstraszella lineata,
      recovered on sunken wood sampled in the western Pacific, close to the Vanuatu
      Islands. The two species display distinctly different associations with bacterial
      partners. Leptochiton boucheti harbours Mollicutes in regions of its gut
      epithelium and has no abundant bacterium associated with its gill. Nierstraszella
      lineata displays no dense gut-associated bacteria, but harbours bacterial
      filaments attached to its gill epithelium, related to the Deltaproteobacteria
      symbionts found in gills of the wood-eating limpet Pectinodonta sp. Stable carbon
      and nitrogen isotope signatures and an absence of cellulolytic activity give
      evidence against a direct wood-feeding diet; both species are secondary consumers
      within the wood food web. We suggest that the distinct associations with
      bacterial partners are linked to niche specialisations of the two species.
      Nierstraszella lineata is in a taxonomic family restricted to sunken wood and is
      possibly adapted to more anoxic conditions thanks to its gill-associated
      bacteria. Leptochiton boucheti is phylogenetically more proximate to an ancestral
      form not specialised on wood and may itself be more of a generalist; this
      observation is congruent with its association with Mollicutes, a bacterial clade
      comprising gut-associated bacteria occurring in several metazoan phyla.

PMID- 22988942
TI  - Smoking during pregnancy: changes in mid-gestation angiogenic factors in women at
      risk of developing preeclampsia according to uterine artery Doppler findings.
AB  - OBJECTIVES: To ascertain whether angiogenic factors are altered in smokers at
      increased risk of preeclampsia (PE) according to uterine artery Doppler (UAD)
      assessment. METHODS: Uterine artery mean pulsatility index (PI), maternal
      placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)
      serum levels were measured in 125 healthy pregnant women at 24 weeks of
      gestation. Smoking status was determined based on cotinine levels in maternal
      blood. RESULTS: Smokers had significantly higher PlGF concentration compared with
      nonsmokers [median PlGF levels: 575 (511) vs. 277 (259) pg/mL, respectively, p =
      0.001]. The differences in PlGF levels were also observed between smokers and
      nonsmokers within the group of women with abnormal UAD and therefore at high risk
      of developing PE [median PlGF levels: 472 (434) vs. 235 (169) pg/mL,
      respectively, p = 0.0005]. In our patient cohort, 16 women developed PE (12.8%),
      of whom only 3 were smokers [odds ratios (ORs): 0.49; 95% confidence interval
      (CI) (0.13-1.84)]. In patients who finally developed intrauterine growth
      restriction, the PlGF/sFlt-1 ratio was significantly higher in the group of
      smokers compared with that of nonsmokers [0.39 (0.28) vs. 0.13 (0.21),
      respectively, p = 0.0311]. CONCLUSION: The effect of smoking in reducing the risk
      of PE may be due to the increase of PlGF and PlGF/sFlt-1 ratio in maternal blood,
      even among women with abnormal UAD.

PMID- 22988943
TI  - Computed tomography of coxofemoral injury in five mute swans (Cygnus olor).
AB  - Five mute swans (Cygnus olor) were presented with inability to stand or with
      abnormal positioning of a leg. Clinical examinations indicated the possibility of
      femoral fractures or coxofemoral luxations. The suspected diagnosis was proven by
      means of computed tomography (CT), while superimposition of gastrointestinal
      contents or other artefacts limited radiographic diagnosis in three birds. A
      typical CT sign for lesions of the coxofemoral joint apart from femoral
      displacement was haemorrhage within the pelvic bones (especially around the
      acetabulum), found in four of the five birds. Small femoral head avulsion
      fractures could be detected only with CT.

PMID- 22988941
TI  - Acid-triggered release via dePEGylation of fusogenic liposomes mediated by
      heterobifunctional phenyl-substituted vinyl ethers with tunable pH-sensitivity.
AB  - A new family of heterobifunctional phenyl-substituted vinyl ether (PIVE) coupling
      agents with tunable acid-sensitivity has been developed. The PIVE compounds are
      designed to hydrolyze under acidic conditions with hydrolysis rates that can be
      varied by rational selection of the phenyl ring substituent. These reagents were
      incorporated within 2-methoxypoly(ethylene glycol) PEG-conjugated 1,3-dioctadecyl
      rac-glycerol lipids to produce the acid-cleavable lipopolymers mPEG-[H-PIVE]-DOG,
      mPEG-[F-PIVE]-DOG, mPEG-[Me-PIVE]-DOG, and mPEG-[MeO-PIVE]-DOG. These
      lipopolymers were hydrolyzed under acidic conditions (pH 3.5 or 4.5) at rates
      that were dependent on the electron donating or withdrawing character of the
      alpha-phenyl vinyl ether substituent, while remaining stable at pH 7.4. Blending
      of these compounds with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in a
      10:90 mPEG-PIVE-Lipid:DOPE ratio produced stable liposomes at neutral pH;
      however, acidification of the solution led to dePEGylation and release of the
      liposomal cargo in a manner that correlated with the PIVE proton affinity.
      Specifically, we observed 70% calcein release within 12 h from mPEG-[MeO-PIVE]
      DOG-containing liposomes at pH 4.5, whereas only 22% calcein release was observed
      from mPEG-[F-PIVE]-DOG:DOPE liposomes over this same time scale and pH. These
      results indicate that dePEGylation following acidification is a triggering
      mechanism that can be rationally designed and controlled through the appropriate
      selection of PIVE moieties.

PMID- 22988945
TI  - Ring-closing metathesis/isomerization/Pictet-Spengler cascade via
      ruthenium/chiral phosphoric acid sequential catalysis.
AB  - Chiral phosphoric acid worked together with Hoveyda-Grubbs II catalyst enabling
      highly efficient synthesis of enantioenriched tetrahydro-beta-carbolines (up to
      98% yield, 99% ee) through a ring-closing metathesis/isomerization/Pictet
      Spengler cascade reaction via sequential catalysis.

PMID- 22988944
TI  - Network-based SNP meta-analysis identifies joint and disjoint genetic features
      across common human diseases.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have provided a large set of
      genetic loci influencing the risk for many common diseases. Association studies
      typically analyze one specific trait in single populations in an isolated fashion
      without taking into account the potential phenotypic and genetic correlation
      between traits. However, GWA data can be efficiently used to identify overlapping
      loci with analogous or contrasting effects on different diseases. RESULTS: Here,
      we describe a new approach to systematically prioritize and interpret available
      GWA data. We focus on the analysis of joint and disjoint genetic determinants
      across diseases. Using network analysis, we show that variant-based approaches
      are superior to locus-based analyses. In addition, we provide a prioritization of
      disease loci based on network properties and discuss the roles of hub loci across
      several diseases. We demonstrate that, in general, agonistic associations appear
      to reflect current disease classifications, and present the potential use of
      effect sizes in refining and revising these agonistic signals. We further
      identify potential branching points in disease etiologies based on antagonistic
      variants and describe plausible small-scale models of the underlying molecular
      switches. CONCLUSIONS: The observation that a surprisingly high fraction (>15%)
      of the SNPs considered in our study are associated both agonistically and
      antagonistically with related as well as unrelated disorders indicates that the
      molecular mechanisms influencing causes and progress of human diseases are in
      part interrelated. Genetic overlaps between two diseases also suggest the
      importance of the affected entities in the specific pathogenic pathways and
      should be investigated further.

PMID- 22988946
TI  - Outpatient prescription practices in rural township health centers in Sichuan
      Province, China.
AB  - BACKGROUND: Sichuan Province is an agricultural and economically developing
      province in western China. To understand practices of prescribing medications for
      outpatients in rural township health centers is important for the development of
      the rural medical and health services in this province and western China.
      METHODS: This is an observational study based on data from the 4th National
      Health Services Survey of China. A total of 3,059 prescriptions from 30 township
      health centers in Sichuan Province were collected and analyzed. Seven indicators
      were employed in the analyses to characterize the prescription practices. They
      are disease distribution, average cost per encounter, number of medications per
      encounter, percentage of encounters with antibiotics, percentage of encounters
      with glucocorticoids, percentage of encounters with combined glucocorticoids and
      antibiotics, and percentage of encounters with injections. RESULTS: The average
      medication cost per encounter was 16.30 Yuan ($2.59). About 60% of the
      prescriptions contained Chinese patent medicine (CPM), and almost all
      prescriptions (98.07%) contained western medicine. 85.18% of the prescriptions
      contained antibiotics, of which, 24.98% contained two or more types of
      antibiotics; the percentage of prescriptions with glucocorticoids was 19.99%; the
      percentage of prescriptions with both glucocorticoids and antibiotics was 16.67%;
      51.40% of the prescriptions included injections, of which, 39.90% included two or
      more injections. CONCLUSIONS: The findings from this study demonstrated
      irrational medication uses of antibiotics, glucocorticoids and injections
      prescribed for outpatients in the rural township health centers in Sichuan
      Province. The reasons for irrational medication uses are not only solely due to
      the pursuit of maximizing benefits in the township health centers, but also more
      likely attributable to the lack of medical knowledge of rational medication uses
      among rural doctors and the lack of medical devices for disease diagnosis in
      those township health centers. The policy implication from this study is to
      enhance professional training in rational medication uses for rural doctors,
      improve hardware facilities for township health centers, promote health education
      to rural residents and establish a public reporting system to monitor
      prescription practices in rural township health centers, etc.

PMID- 22988947
TI  - The waiting room: vector for health education? The general practitioner's point
      of view.
AB  - BACKGROUND: General practitioners (GPs) play a central role in disseminating
      information and most health policies are tending to develop this pivotal role of
      GPs in dissemination of health-related information to the public. The objective
      of this study was to evaluate use of the waiting room by GPs as a vector for
      health promotion. RESULTS: A cross-sectional study was conducted on a
      representative sample of GPs using semi-structured, face-to-face interviews. A
      structured grid was used to describe the documents. Quantitative and qualitative
      analysis was performed. Sixty GPs participated in the study. They stated that a
      waiting room had to be pleasant, but agreed that it was a useful vector for
      providing health information. The GPs stated that they distributed documents
      designed to improve patient care by encouraging screening, providing health
      education information and addressing delicate subjects more easily. However, some
      physicians believed that this information can sometimes make patients more
      anxious. A large number of documents were often available, covering a variety of
      topics. CONCLUSION: General practitioners intentionally use their waiting rooms
      to disseminate a broad range of health-related information, but without
      developing a clearly defined strategy. It would be interesting to correlate the
      topics addressed by waiting room documents with prevention practices introduced
      during the visit.

PMID- 22988948
TI  - Genetic linkages for thyroxine released in response to thyrotropin stimulation in
      three sets of recombinant inbred mice provide evidence for shared and novel genes
      controlling thyroid function.
AB  - BACKGROUND: Graves' hyperthyroidism is induced by immunizing mice with adenovirus
      expressing the human thyrotropin (TSH)-receptor. Using families of recombinant
      inbred mice, we previously discovered that genetic susceptibility to induced
      thyroid-stimulating antibodies and hyperthyroidism are linked to loci on
      different chromosomes, indicating a fundamental genetic difference in thyroid
      sensitivity to ligand stimulation. An approach to assess thyroid sensitivity
      involves challenging genetically diverse lines of mice with TSH and measuring the
      genotype/strain-specific increase in serum thyroxine (T4). METHODS: We
      investigated genetic susceptibility and genetic control of T4 stimulation by 10
      mU bovine TSH in female mice of the CXB, BXH, and AXB/BXA strain families, all
      previously studied for induced Graves' hyperthyroidism. RESULTS: Before TSH
      injection, T4 levels must be suppressed by inhibiting endogenous TSH secretion.
      Three daily intraperitoneal L-triiodothyronine injections efficiently suppressed
      serum T4 in females of 50 of 51 recombinant inbred strains. T4 stimulation by TSH
      was more strongly linked in CXB and BXH sets, derived from parental strains with
      divergent T4 stimulation, than in AXB/BXA strains generated from parents with
      similar TSH-induced responses. Genetic loci linked to the acute TSH-induced T4
      response (hours) were not the same as those linked to induced hyperthyroidism
      (which develops over months). CONCLUSIONS: Genetic susceptibility for thyroid
      sensitivity to TSH stimulation was distinct for three families of inbred mouse
      lines. These observations parallel the human situation with multiple genetic loci
      contributing to the same trait and different loci associated with the same trait
      in different ethnic groups. Of the genetic loci highlighted in mice, three
      overlap with, or are located up or downstream, of human TSH-controlling genes.
      Other studies show that human disease genes can be identified through cross
      species gene mapping of evolutionary conserved processes. Consequently, our
      findings suggest that novel thyroid function genes may yet be revealed in humans.

PMID- 22988949
TI  - Site-isolated redox reactivity in a trinuclear iron complex.
AB  - The symmetric, high-spin triiron complex ((Ph)L)Fe(3)(THF)(3) reacts with mild
      chemical oxidants (e.g., Ph(3)C-X, I(2)) to afford an asymmetric core, where one
      iron bears the halide ligand ((Ph)L)Fe(3)X(L) and the hexadentate ((Ph)L =
      MeC(CH(2)NPh-o-NPh)(3)) ligand has undergone significant rearrangement. In the
      absence of a suitable trapping ligand, the chlorine and bromine complexes form
      (MU-X)(2)-bridged structures of the type [((Ph)L)Fe(3)(MU-X)](2). In the
      trinuclear complexes, the halide-bearing iron site sits in approximate trigonal
      bipyramidal (tbp) geometry, formed by two ((Ph)L) anilides and an exogenous
      solvent molecule. The two distal iron atoms reside in distorted square-planar
      sites featuring a short Fe-Fe separation at 2.301 A, whereas the distance to the
      tbp site is substantially elongated (2.6-2.7 A). Zero-field, (57)Fe Mossbauer
      analysis reveals the diiron unit as the locus of oxidation, while the tbp site
      bearing the halide ligand remains divalent. Magnetic data acquired for the series
      reveal that the oxidized diiron unit comprises a strongly coupled S = (3)/(2)
      unit that is weakly ferromagnetically coupled to the high-spin (S = 2) ferrous
      site, giving an overall S = (7)/(2) ground state for the trinuclear units.

PMID- 22988950
TI  - Protein and steroid profiles in follicular fluid after ovarian hyperstimulation
      as potential biomarkers of IVF outcome.
AB  - Controlled ovarian hyperstimulation is performed to assist with generation of
      multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our
      study was to evaluate differences in protein and steroid profiles in ovarian
      follicular fluid (hFF) samples obtained during oocyte retrieval from women
      undergoing IVF treatment and to identify physiological pathways associated with
      the proteins. The hFF samples were depleted of abundant proteins, fractionated by
      ultrafiltration, digested, and analyzed by nano-LC-QTOF. Concentrations of 15
      endogenous steroids were determined in the samples using LC-MS/MS methods. The
      total number of proteins identified in the samples was 75, of which 4, 7, and 2
      were unique to the samples from women with viable pregnancy, miscarriage, and no
      pregnancy, respectively. Identified proteins were associated with the acute
      response signaling, coagulation system, intrinsic and extrinsic prothrombin
      activation, complement system, neuroprotective role of THOP1, FXR/RXR activation,
      role of tissue factor, and growth hormone pathways. A greater number of proteins
      associated with biosynthesis was found in hFF samples corresponding to the
      oocytes resulting in pregnancy. The abundance of seven proteins was found to be
      associated with steroidogenesis. The obtained data will contribute to better
      understanding of the pathogenesis and development of noninvasive markers for
      assessment of oocytes viability.

PMID- 22988951
TI  - Functional gastrointestinal disorders in adolescents and quality of school life.
AB  - BACKGROUND AND AIM: The prevalence of functional gastrointestinal disorders
      (FGID) in adolescents and their relationship to quality of school life (QOSL) are
      not fully understood. This study investigated the relationship between FGID and
      QOSL. METHODS: Adolescents (10-17 years) were recruited from 40 schools. FGID
      diagnoses were based on the Questionnaire on Pediatric Gastrointestinal Symptoms
      Rome III version (QPGS-RIII). QOSL was evaluated by a questionnaire and
      calculated as the QOSL score. RESULTS: Five hundred and fifty-two of the 3976
      students (13.9%) met the FGID criteria for one or more diagnoses according to the
      QPGS-RIII: 12.3% met the criteria for one, 1.5% for two or more. Irritable bowel
      syndrome (IBS) was the most common diagnosis (5.9%) followed by functional
      abdominal pain (3.1%). The prevalence of FGID was significantly higher in the
      female students in comparison to male students (P < 0.01). The prevalence of FGID
      was 9.5% in elementary school, 15.4% in junior high school, 26.0% in high school
      students, respectively. The prevalence of FGID was significantly increased with
      age (P < 0.01). The QOSL score of the patients with FGID was 10.9 +/- 4.5 and
      that without FGID was 8.2 +/- 2.8, respectively. The QOSL score of the patients
      with FGID was significantly worse than those without FGID (P < 0.01). The QOSL
      scores with IBS, aerophagia, and cyclic vomiting syndrome were significantly
      worse among the FGID (P < 0.01). CONCLUSIONS: The prevalence of FGID in
      adolescents was relatively high. The presences of FGID worsen the QOSL score.
      Medical intervention and/or counseling are needed for such students to improve
      the QOSL.

PMID- 22988952
TI  - Diabetes treatment: the coming paradigm shift.

PMID- 22988953
TI  - Psychological distress among university female students and their need for mental
      health services.
AB  - Psychological distress among university students, especially young women, is of
      increasing concern. This study focuses on the prevalence of psychological
      distress among female university students and their need for mental health
      services. The analysis is based on two cross-sectional surveys, an internet
      survey among women students attending the University of Iceland in the spring of
      2007, and a postal survey of Icelandic female adults conducted in the Fall of
      2006. Psychological distress was measured with the Symptom Checklist-90
      Depression and Anxiety subscales. The prevalence of above-threshold depression
      and anxiety among the university women students was 22.5% and 21.2% respectively.
      Results showed that the mean depression score was significantly lower among the
      students than among women of the same age in the general population. However,
      little less than one-third of students with elevated distress levels received any
      professional help. Only 1.4% of the distressed students received mental help care
      from nurses. The high proportion of distressed female students not receiving
      professional help is a challenge to the primary health-care system and the
      nursing profession. This also raises questions about the adequacy of the current
      system of health-care delivery and the potential advantages of on-campus health
      services, in closer proximity to the students.

PMID- 22988955
TI  - Migratory response of Echinostoma caproni (Digenea: Echinostomatidae) to feeding
      by ICR mice.
AB  - The migratory response of Echinostoma caproni to host feeding was examined in
      female ICR mice. Thirty-six mice were each infected with 20 metacercariae of E.
      caproni . Twenty-eight days post-infection, food, but not water, was withheld for
      24 hr. Mice were haphazardly divided into 4 groups of 9, and each group received
      one of the following treatments: (1) 0.25 g glucose, (2) access to standard lab
      chow, (3) 0.5 ml saline, and (4) continued fasting. Three mice from each
      treatment group were killed 1, 2, and 4 hr post-treatment. The intestine of each
      mouse was removed, flash-frozen, and stored in a conventional freezer for later
      examination. Intestines were partially thawed, measured, and opened
      longitudinally, and the position of each worm, or worm cluster was measured. The
      intestine was divided into equal 5% segments based on the initial measurement and
      locations of worms, and worm clusters were recorded from the appropriate section
      of the intestine for analysis. There was no significant effect of treatment in
      the position of worms at 1 hr. There was a posterior shift in worm position in
      all treatment groups at 2 hr, except in the saline-treated mice; however, only
      worms in the glucose-fed mice were significantly posterior to the unfed controls.
      From 2 to 4 hr, there was a significant anterior movement of worms in both the
      glucose and chow-fed mice. The data strongly suggest that E. caproni responds to
      the initiation of gastric activity of the host by migrating anteriorly in the
      ileum. The specific stimulus for this migration is unknown.

PMID- 22988956
TI  - Limitations of targeted therapy with sorafenib in elderly high-risk
      myelodysplastic syndrome and acute myeloid leukemia.

PMID- 22988957
TI  - Actin filament motility induced variation of resonance frequency and rigidity of
      polymer surfaces studied by quartz crystal microbalance.
AB  - This contribution reports on the quantification of the parameters of the motility
      assays for actomyosin system using a quartz crystal microbalance (QCM). In
      particular, we report on the difference in the observed resonance frequency and
      dissipation of a quartz crystal when actin filaments are stationary as opposed to
      when they are motile. The changes in QCM measurements were studied for various
      polymer-coated surfaces functionalized with heavy meromyosin (HMM). The results
      of the QCM experiments show that the HMM-induced sliding velocity of actin
      filaments is modulated by a combination of the viscoelastic properties of the
      polymer layer including the HMM motors.

PMID- 22988958
TI  - The distribution of axial length, anterior chamber depth, lens thickness, and
      vitreous chamber depth in an adult population of Shahroud, Iran.
AB  - BACKGROUND: Ocular biometric parameters can be influenced by race, ethnicity, and
      genetics; their differences across different populations can probably explain
      differences in refractive errors in these populations. The aim of this study is
      to determine the normal range of axial length, anterior chamber depth, lens
      thickness, and vitreous chamber depth in the population of Shahroud in the north
      of Iran. METHODS: In the first phase of Shahroud Eye Cohort Study, the 40-64 year
      old population were sampled cross-sectionally; 6311 were invited and 5190 (82.2%)
      participated in the study. Biometric examinations were done using the
      LENSTAR/BioGraph (WaveLight AG, Erlangen, Germany) after vision tests and before
      cycloplegic refraction tests. Any type of eye surgery, extensive pterygium, and
      lack of cooperation were used as exclusion criteria, and analyses were done with
      data from 4869 eyes. RESULTS: We found a mean axial length of 23.14 mm (95%
      confidence interval [CI], 23.11-23.17), mean anterior chamber depth of 2.62 mm
      (95% CI, 2.60-2.63), mean lens thickness of 4.28 mm (95% CI, 4.27-4.29), and the
      mean vitreous chamber depth was 15.72 mm (95% CI, 15.70-15.75).Kolmogorov-Smirnov
      tests showed that the distribution of axial length, anterior chamber depth, lens
      thickness, and vitreous chamber depth significantly differed from normal; axial
      length and vitreous chamber depth demonstrated a leptokurtic distribution as
      well.Axial length, anterior chamber depth, and vitreous chamber depth
      significantly decreased with age, and lens thickness significantly increased with
      age (p < 0.001). All indices were significantly higher in men. CONCLUSIONS: The
      distributions of axial length, vitreous chamber depth, and lens thickness are
      reported for the first time in an Iranian adult population. Compared to other
      studies, axial length was in the mid range, nonetheless, studying axial length
      components showed that the Iranian population had smaller anterior chamber depth
      and lens thickness. Age and gender were significantly associated with all indices
      assessed in this study.

PMID- 22988959
TI  - Canine dacryolithiasis: a case description and mineral analysis.
AB  - A 4-year-old, female, spayed, Labrador retriever was presented with a painless
      swelling of the left ventromedial eyelid and epiphora of 3 months duration.
      Bilateral patency of the nasolacrimal system was confirmed by the appearance of
      fluorescein dye at both nares. Ultrasonography revealed a well-demarcated fluid
      filled structure containing echogenic ill-defined material in close proximity to
      the nasolacrimal system. A transconjunctival surgical approach confirmed the
      close anatomical proximity of the cyst and the absence of a communication with
      the inferior canaliculus. The cyst contained multiple intraluminal calculi
      (dacryoliths). Following surgical excision of the cyst, the epiphora resolved and
      no recurrence was noted over a 12-month follow-up period. On histopathology, the
      cystic structure was lined by stratified squamous epithelium, consistent with
      lacrimal canaliculus epithelium. Presumed progression of a canalicular
      diverticulum to a cyst with the formation of intraluminal dacryoliths was
      suspected. Mineral analysis of the dacryoliths revealed a calcium carbonate
      composition.

PMID- 22988960
TI  - TPA for ischemic stroke in patients >=80 years.
AB  - OBJECTIVE: Although patients >80 years were excluded in RCTs for tPA treatment of
      acute ischemic stroke (AIS), many centers treat old patients. We wanted to
      examine whether age >=80 years is an independent predictor of outcome after tPA.
      MATERIALS: We included 77 consecutive patients >=80 years and 83 patients <80
      years treated with tPA within 4.5 h after onset of AIS. Baseline variables were
      analyzed by multiple stepwise logistic regression analyses against three
      outcomes: symptomatic intracerebral hemorrhage (sICH), death and good functional
      outcome (mRS, 0-1) at 3-month follow-up. RESULTS: Age >=80 years was associated
      with increased risk of sICH (OR, 18.2 [95% CI, 1.0-324.1], P = 0.048), and death
      (OR, 3.3 [95% CI, 1.2-9.1], P = 0.018), but not with functional outcome at 3
      months. Other factors associated with death were longer onset to treatment time
      (OTT) (OR, 1.007/min increase [95% CI, 1.00-1.015], P = 0.047), higher NIHSS (OR,
      1.12 per point increase [95% CI, 1.04-1.19], P = 0.001), and previous stroke (OR,
      4.0 [95% CI, 1.2-13.7], P = 0.03). Predictors of good functional outcome were
      shorter OTT (OR, 0.99 [95% CI, 0.98-1.00], P = 0.02) and lower NIHSS (OR, 0.80
      [95% CI, 0.74-0.87] P <= 0.001). CONCLUSION: Age >=80 years might be an
      independent risk factor for sICH and death the first 3 months after treatment
      with tPA for AIS, but does not influence the chance of a good functional outcome.
      We suggest to treat patients over 80 years with tPA, but be cautious if the time
      from onset (OTT) is long.

PMID- 22988961
TI  - Racial differences in long-term outcomes after percutaneous coronary intervention
      with paclitaxel-eluting coronary stents.
AB  - OBJECTIVES: To assess the influence of race on long-term outcomes following
      percutaneous coronary intervention (PCI) with paclitaxel-eluting stents (PES).
      BACKGROUND: Data on the influence of race on long-term outcomes following PCI
      with drug-eluting stents are limited because of severe underrepresentation of
      minority populations in randomized trials. METHODS: We compared 5-year outcomes
      of 2,301 whites, 127 blacks, and 169 Asians treated with PES in the TAXUS IV, V,
      and ATLAS trials. Outcomes were adjusted using a propensity score logistic
      regression model with 1:4 matching. RESULTS: Blacks were more likely than whites
      to be female, have a history of hypertension, diabetes mellitus, congestive heart
      failure, and stroke, but were less likely to have prior coronary artery disease.
      Compared with whites, Asians were younger, more likely to be male, have stable
      angina, and left anterior descending disease, and less likely to have silent
      ischemia, previous coronary artery bypass surgery, prior coronary artery disease,
      diabetes mellitus, peripheral vascular disease, and to receive glycoprotein
      IIb/IIIa inhibitors. Despite higher antiplatelet compliance, the adjusted 5-year
      rates of myocardial infarction (15.4% vs. 5.4%, P < 0.001) and stent thrombosis
      (5.6% vs. 1.1%, P = 0.002) were higher in blacks than whites. Despite lower
      antiplatelet compliance, Asians had no differences in myocardial infarction and
      stent thrombosis compared with whites. Mortality and revascularization rates were
      similar between the three groups. CONCLUSIONS: The long-term risk of major
      thrombotic events after PCI with PES was higher in blacks, but not Asians,
      compared with whites. The mechanisms underlying these racial differences warrant
      further investigation.

PMID- 22988962
TI  - Ligand-gated ion channels: new insights into neurological disorders and ligand
      recognition.

PMID- 22988963
TI  - Stability studies of HIV-1 Pr55gag virus-like particles made in insect cells
      after storage in various formulation media.
AB  - BACKGROUND: HIV-1 Pr55gag virus-like particles (VLPs) expressed by baculovirus in
      insect cells are considered to be a very promising HIV-1 vaccine candidate, as
      they have been shown to elicit broad cellular immune responses when tested in
      animals, particularly when used as a boost to DNA or BCG vaccines. However, it is
      important for the VLPs to retain their structure for them to be fully functional
      and effective. The medium in which the VLPs are formulated and the temperature at
      which they are stored are two important factors affecting their stability.
      FINDINGS: We describe the screening of 3 different readily available formulation
      media (sorbitol, sucrose and trehalose) for their ability to stabilise HIV-1
      Pr55gag VLPs during prolonged storage. Transmission electron microscopy (TEM) was
      done on VLPs stored at two different concentrations of the media at three
      different temperatures (4 degrees C, -20 degrees C and -70 degrees C) over
      different time periods, and the appearance of the VLPs was compared. VLPs stored
      in 15% trehalose at -70 degrees C retained their original appearance the most
      effectively over a period of 12 months. VLPs stored in 5% trehalose, sorbitol or
      sucrose were not all intact even after 1 month storage at the temperatures
      tested. In addition, we showed that VLPs stored under these conditions were able
      to be frozen and re-thawed twice before showing changes in their appearance.
      CONCLUSIONS: Although the inclusion of other analytical tools are essential to
      validate these preliminary findings, storage in 15% trehalose at -70 degrees C
      for 12 months is most effective in retaining VLP stability.

PMID- 22988964
TI  - Low neutral genetic variability in a specialist puffin hunter: the Norwegian
      Lundehund.
AB  - The genetic variability of 125 Norwegian Lundehund and 27 Nova Scotia Duck
      Tolling Retriever was analysed using a set of 26 microsatellite markers. In
      Lundehund, the average number of alleles per locus was 1.73, and average observed
      (H(O)) and expected (H(E)) heterozygosity were 0.07. In Toller, all measures of
      genetic diversity were much higher than in Lundehund and similar to studies on
      other dog breeds. The cluster analysis correctly assigned individuals to their
      respective breed. The low genetic variability in Lundehund was not surprising,
      given the two strong bottlenecks in the 1940s and the 1960s. The relatedness of
      Lundehund to other Nordic small spitzes should be investigated in the view of
      possible outcrossing.

PMID- 22988965
TI  - Endocardial mapping and catheter ablation for ventricular fibrillation prevention
      in Brugada syndrome.
AB  - Endocardial Mapping and Ablation of Brugada Syndrome. INTRODUCTION: Brugada
      syndrome (BS) is characterized by ST-segment elevation in the right precordial
      electrocardiogram (ECG) leads and episodes of ventricular fibrillation (VF). This
      study aimed to observe the feasibility of substrate modification by
      radiofrequency catheter ablation and its effects on VF storm. METHODS AND
      RESULTS: Ten BS patients (all men; median age 36.5 years) with VF storm (group I,
      n = 4) and no VF storm (group II, n = 6) were enrolled in the study between
      August 2007 and December 2008. All patients underwent electrophysiological study
      using noncontact mapping. The multielectrode array was placed in the right
      ventricular outflow tract (RVOT). The isopotential map was analyzed during sinus
      rhythm and the region that had electrical activity occurring during J point to
      +60 (J+60) milliseconds interval of the V1 or V2 of surface ECG was considered as
      the late activation zone (LAZ) and also the substrate for ablation. LAZ was found
      in RVOT with variable distribution in both groups. Endocardial catheter ablation
      of the LAZ modified Brugada ECG pattern in 3 of 4 patients (75%) and suppressed
      VF storm in all 4 patients in group I during long-term follow-up (12-30 months).
      One patient had complete right bundle branch block from the ablation procedure.
      CONCLUSIONS: LAZ on RVOT identified by noncontact mapping may serve as potential
      VF substrate in BS patients with VF episodes. Radiofrequency ablation on LAZ
      normalized ECG, suppressed VF storm, and reduced VF recurrence. The procedure is
      safe and may prevent VF occurrence.

PMID- 22988967
TI  - Application of strain-promoted azide-alkyne cycloaddition and tetrazine ligation
      to targeted Fc-drug conjugates.
AB  - We have previously described an approach whereby antibody Fc fragments harboring
      a single C-terminal selenocysteine residue (Fc-Sec) are directed against a
      variety of targets by changing the peptide or small molecule to which they are
      conjugated. In the present work, we describe methodology for improving the
      efficacy of these Fc-Sec conjugates by incorporating cytotoxic drugs. The Fc-Sec
      protein is first programmed to target specific tumor cell types by attachment of
      a bifunctional linker that contains a "clickable" handle (e.g., cyclobutane or
      cyclooctyne) in addition to a tumor cell-binding peptide or small molecule.
      Following Fc-Sec conjugation, a cytotoxic warhead is then attached by
      cycloaddition reactions of tetrazine or azide-containing linker. To validate this
      approach, we used a model system in which folic acid (FA) is the targeting moiety
      and a disulfide-linked biotin moiety serves as a cytotoxic drug surrogate. We
      demonstrated successful targeting of Fc-Sec proteins to folate-receptor
      expressing tumor cells. Tetrazine ligation was found to be an efficient method
      for biotin "arming" of the folate-targeted Fc-Sec proteins. We also report novel
      bioconjugation methodologies that use [4 + 2] cycloaddition reactions between
      tetrazines and cyclooctynes.

PMID- 22988966
TI  - Crystal structure of the MrkD1P receptor binding domain of Klebsiella pneumoniae
      and identification of the human collagen V binding interface.
AB  - Klebsiella species are members of the family enterobacteriaceae, opportunistic
      pathogens that are among the eight most prevalent infectious agents in hospitals.
      Among other virulence factors in Klebsiella, type 3 pili exhibit a unique binding
      pattern in the human kidney via interaction of two MrkD adhesion variants 1C1 and
      1P to type IV and/or V collagen. However, very little is known about the nature
      of this recognition. Here we present the crystal structure of the plasmid born
      MrkD1P receptor domain (MrkDrd). The structure reveals a jelly-roll beta-barrel
      fold comprising 17 beta-strands very similar to the receptor domain of GafD, the
      tip adhesin from the F17 pilus that recognizes n-acetyl-d-glucosamine (GlcNAc).
      Analysis of collagen V binding of different MrkD1P mutants revealed that two
      regions were responsible for its binding: a pocket, that aligns approximately
      with the GlcNAc binding pocket of GafD involving residues R105 and Y155, and a
      transversally oriented patch that spans strands beta2a, beta9b and beta6
      including residues V49, T52, V91, R102 and I136. Taken together, these data
      provide structural and functional insights on MrkD1P recognition of host cells,
      providing a tool for future development of rationally designed drugs with the
      prospect of blocking Klebsiella adhesion to collagen V.

PMID- 22988968
TI  - Arsenic trioxide-induced growth arrest of breast cancer MCF-7 cells involving
      FOXO3a and IkappaB kinase beta expression and localization.
AB  - Currently, arsenic has been clinically investigated as a therapeutic agent for a
      variety of solid malignancies, including breast cancer. However, the exact
      underlying molecular mechanisms through which arsenic trioxide (As(2)O(3))
      induces cell growth arrest and apoptosis in solid tumors have not been clearly
      understood. The aim of our study was to gain an insight into the effect of
      As(2)O(3) on the human breast cancer MCF-7 cell line and investigate cell growth
      inhibition, apoptosis, and the molecular mechanism after As(2)O(3) treatment in
      MCF-7 cells. Expression of FOXO3a, nuclear-FOXO3a, caspase-3, and IkappaB kinase
      beta (IKKbeta) mRNA levels in MCF-7 cells was determined by reverse transcription
      polymerase chain reaction (RT-PCR). The protein expression was examined by the
      Western blot analysis and immunocytochemical staining. The distribution of
      apoptotic cells was assessed by flow cytometry, and the morphology of the
      apoptotic cells was investigated by Hoechest33258 staining. Our results showed
      that As(2)O(3) significantly induced the apoptosis of MCF-7 cells tested in this
      study in a dose-dependent manner. As(2)O(3) induced the decrease of IKKbeta
      expression and the increase of total as well as nuclear FOXO3a expression, which
      triggered the phosphorylation of cytoplasmic FOXO3a at the Thr32 residue
      decrease. RT-PCR, Western blot analysis, and immunocytochemistry revealed that
      the expression of IKKbeta in MCF-7 cells was upregulated when As(2)O(3) was
      combined with tumor necrosis factor-alpha (TNF-alpha), whereas the expression of
      FOXO3a was downregulated in comparison with the As(2)O(3)-alone group. These
      findings indicated a specific molecular mechanism by which MCF-7 cell lines were
      susceptible to the As(2)O(3) therapy through FOXO3a expression and localization.
      This FOXO3a accumulation may be well correlated with the As(2)O(3)-induced
      reduction of active IKKbeta, which may provide new insights into As(2)O(3)
      related signaling activities.

PMID- 22988970
TI  - Preparation and characterization of nano-liposome-mediated FL gene in the Lovo
      cells.
AB  - AIMS: The purpose of the present work was to formulate and evaluate cationic nano
      liposomes as novel nonviral gene delivery for colon cancer treatment. METHODS:
      Recombinant pEGFP-c1-Fms-like tyrosine kinase receptor 3 ligand (FL) plasmids
      containing human FL gene and green fluorescent protein (GFP) reporter genes were
      constructed. FL and GFP Gene-carrying cationic nano-liposomes were prepared based
      on the electrostatic adherence principle and then transfected into Lovo cells.
      The morphology, particle size, and zeta potential of gene-carrying cationic nano
      liposomes were observed using an electron microscope. GFP expression was observed
      by fluorescence microscopy to assay the transfection efficiency. The cytotoxicity
      of FL/nano-liposomes was evaluated by the MTT method. RESULTS: Recombinant
      plasmids pEGFP-c1-FL are successfully constructed using gene cloning methods and
      confirmed by restriction enzyme digestion and sequencing. The cationic nano
      liposomes carrying pEGFP-cl-FL were observed by an electron micrograph and showed
      uniform spherical or elliptical shapes and many pores. The fluorescence
      microscopy images of gene-carrying cationic nano-liposomes showed good expression
      of GFP in pEGFP and pEGFP-cl-FL groups. The MTT assay of cell death indicated a
      significantly higher level of cell death between the FL group and the control
      group at 24, 48, and 96 hours after transplantation. CONCLUSION: Cationic nano
      liposomes show safe and high-performance transfection as gene carriers. Gene
      therapy has significant implications for colon cancer treatment in future.

PMID- 22988969
TI  - Gene therapy of malignant solid tumors by targeting erbB2 receptors and by
      activating T cells.
AB  - One of the strategies to improve the outcome of anti-erbB2-mediated immunotherapy
      is to combine anti-erbB2 antibodies with T-cell-based adoptive immunotherapy,
      which can be achieved by expressing anti-erbB2 mAb on the surface of T cells. A
      single-chain variable fragment (scFv) from an anti-erbB2 mAb has been expressed
      on T cell surface to bind to erbB2-positive cells, and CD3zeta has been expressed
      as a fusion partner at C terminus of this scFv to transduce signals. T cells
      grafted with this chimeric scFv/CD3zeta were able to specifically attack target
      tumor cells with no MHC/Ag restriction. To test the effects of CD28 signal on
      cellular activation and antitumor effectiveness of chimeric scFv/CD3zeta-modified
      T cells, we constructed a recombinant anti-erbB2 scFv/Fc/CD28/CD3zeta gene in a
      retroviral vector. T cells expressing anti-erbB2 scFv/Fc/CD28/CD3zeta
      specifically lyzed erbB2-positive target tumor cells and secreted not only
      interferon-gamma (IFN-gamma) but also IL-2 after binding to their target cells.
      Our data indicate that CD3 and CD28 signaling can be delivered in one molecule,
      which is sufficient for complete T cell activation without exogenous B7/CD28 co
      stimulation.

PMID- 22988971
TI  - Comparison of the effect of functional groups on gas-uptake capacities by fixing
      the volumes of cages A and B and modifying the inner wall of cage C in rht-type
      MOFs.
AB  - Three porous (3,24)-connected rht-type metal-organic frameworks (MOFs),
      [Cu(3)L(H(2)O)(3)].xsolvents (H(6)L(OH) = 4,4',4"
      (hydroxysilanetriyl)tris(triphenyl-3,5-dicarboxylic acid), SDU-6; H(6)L(Me) =
      4,4',4"-(methylsilanetriyl)tris(triphenyl-3,5-dicarboxylic acid), SDU-7;
      H(6)L(iBu) = 4,4',4"-(isobutylsilanetriyl)tris(triphenyl-3,5-dicarboxylic acid),
      SDU-8), have been successfully prepared from [Cu(2)(COO)(4)] paddlewheel SBUs
      (secondary building units) and C(3)-symmetric Si-based hexatopic
      carboxylatelinkers. All porous MOFs are constructed from 3D packing of nanosized
      cuboctahedral, truncated tetrahedral, and truncated octahedral cages. SDU-6-8
      differ only in the functionality of the central Si atom of the hexacarboxylate
      ligands with hydroxyl, methyl, and isobutyl groups, respectively. Gas adsorption
      measurements of activated MOFs suggested that decoration of the cage walls with
      strong polar groups can enhance the adsorption capacities for N(2), H(2), and
      CH(4). SDU-6 with -OH as the functional group possesses high CH(4) uptake (172
      cm(3) cm(-3) at 35 bar), which is very close to DOE target of 180 cm(3) cm(-3).

PMID- 22988972
TI  - A sequential methodology that allows apoptotic cell sorting and FISH analysis in
      human testicular cells.
AB  - The objective of this study was to develop a methodology that permits the
      detection and separation of apoptotic cells in human testicular tissue and their
      subsequent cytogenetic analysis by fluorescence in situ hybridization (FISH). The
      sequential methodology consisted of five steps: 1) enzymatic disaggregation of
      testicular tissue, 2) specific staining of apoptotic cells, 3) cell sorting by
      flow cytometry, 4) cell fixation, and 5) FISH. Enzymatic disaggregation yielded
      cell counts that ranged from 1.7x10(5) to 5x10(6) cells, and viability values
      greater than 72%. The apoptotic (mean +/- SD: 22% +/- 5.3%) and viable (45.5% +/-
      7.3%) populations were identified and selected by flow cytometry and demonstrated
      purity values ranging between 62% and 100%. The paraformaldehyde fixation of the
      selected fractions resulted in cell loss values of less than 10%. The application
      of three treatments before FISH (membrane permeabilization, elimination of
      cytoplasmic components, and re-fixation of the sample) resulted in hybridization
      frequencies of greater than 98%. In both selected fractions, cells of all
      spermatogenic stages and Sertoli cells were identified. The methodology developed
      has enabled the preparation of a cellular suspension with optimal viability and
      counting, the efficient selection of the apoptotic population, and its analysis
      by cytogenetic techniques. The application of this methodology in testicular
      cells should help establish whether there is a direct relationship between
      chromosome anomalies and apoptosis.

PMID- 22988973
TI  - Mini-clusters with mean probabilities for identifying effective siRNAs.
AB  - BACKGROUND: The distinction between the effective siRNAs and the ineffective ones
      is in high demand for gene knockout technology. To design effective siRNAs, many
      approaches have been proposed. Those approaches attempt to classify the siRNAs
      into effective and ineffective classes but they are difficult to decide the
      boundary between these two classes. FINDINGS: Here, we try to split effective and
      ineffective siRNAs into many smaller subclasses by RMP-MiC(the relative mean
      probabilities of siRNAs with the mini-clusters algorithm). The relative mean
      probabilities of siRNAs are the modified arithmetic mean value of three
      probabilities, which come from three Markov chain of effective siRNAs. The mini
      clusters algorithm is a modified version of micro-cluster algorithm. CONCLUSIONS:
      When the RMP-MiC was applied to the experimental siRNAs, the result shows that
      all effective siRNAs can be identified correctly, and no more than 9% ineffective
      siRNAs are misidentified as effective ones. We observed that the efficiency of
      those misidentified ineffective siRNAs exceed 70%, which is very closed to the
      used efficiency threshold. From the analysis of the siRNAs data, we suggest that
      the mini-clusters algorithm with relative mean probabilities can provide new
      insights to the applications for distinguishing effective siRNAs from ineffective
      ones.

PMID- 22988974
TI  - Interactions between alpha-tocopherol and rosmarinic acid and its alkyl esters in
      emulsions: synergistic, additive, or antagonistic effect?
AB  - Many antioxidants can interact to produce synergistic interactions that can more
      effectively inhibit lipid oxidation in foods. Esterification of rosmarinic acid
      produces a variety of compounds with different antioxidant activity due to
      differences in polarity and thus differences in partitioning in oil, water, and
      interfacial regions of oil-in-water emulsions (O/W). Therefore, rosmarinic acid
      and rosmarinate esters provide an interesting tool to study the ability of
      antioxidant to interact in O/W emulsions. In O/W emulsions, rosmarinic acid (R0)
      exhibited the strongest synergistic interaction with alpha-tocopherol while butyl
      (R4) and dodecyl (R12) rosmarinate esters exhibited small synergistic interaction
      and eicosyl rosmarinate esters (R20) exhibited slightly antagonistic interaction.
      Fluorescence quenching and electron paramagnetic resonance (EPR) studies showed
      that water-soluble rosmarinic acid (R0) exhibited more interactions with alpha
      tocopherol than any of the tested esters (R4, R12, R20). This was also confirmed
      in O/W emulsions where R0 altered the formation of alpha-tocopherol quinone and
      alpha-tocopherol increased the formation of caffeic acid from R0. This formation
      of caffeic acid was proposed to be responsible for the synergistic activity of R0
      and alpha-tocopherol since the formation of an additional antioxidant could
      further increase the oxidative stability of the emulsion.

PMID- 22988975
TI  - A global model of malaria climate sensitivity: comparing malaria response to
      historic climate data based on simulation and officially reported malaria
      incidence.
AB  - BACKGROUND: The role of the Anopheles vector in malaria transmission and the
      effect of climate on Anopheles populations are well established. Models of the
      impact of climate change on the global malaria burden now have access to high
      resolution climate data, but malaria surveillance data tends to be less precise,
      making model calibration problematic. Measurement of malaria response to
      fluctuations in climate variables offers a way to address these difficulties.
      Given the demonstrated sensitivity of malaria transmission to vector capacity,
      this work tests response functions to fluctuations in land surface temperature
      and precipitation. METHODS: This study of regional sensitivity of malaria
      incidence to year-to-year climate variations used an extended Macdonald Ross
      compartmental disease model (to compute malaria incidence) built on top of a
      global Anopheles vector capacity model (based on 10 years of satellite climate
      data). The predicted incidence was compared with estimates from the World Health
      Organization and the Malaria Atlas. The models and denominator data used are
      freely available through the Eclipse Foundation's Spatiotemporal Epidemiological
      Modeller (STEM). RESULTS: Although the absolute scale factor relating reported
      malaria to absolute incidence is uncertain, there is a positive correlation
      between predicted and reported year-to-year variation in malaria burden with an
      averaged root mean square (RMS) error of 25% comparing normalized incidence
      across 86 countries. Based on this, the proposed measure of sensitivity of
      malaria to variations in climate variables indicates locations where malaria is
      most likely to increase or decrease in response to specific climate factors.
      Bootstrapping measures the increased uncertainty in predicting malaria
      sensitivity when reporting is restricted to national level and an annual basis.
      Results indicate a potential 20x improvement in accuracy if data were available
      at the level ISO 3166-2 national subdivisions and with monthly time sampling.
      CONCLUSIONS: The high spatial resolution possible with state-of-the-art numerical
      models can identify regions most likely to require intervention due to climate
      changes. Higher-resolution surveillance data can provide a better understanding
      of how climate fluctuations affect malaria incidence and improve predictions. An
      open-source modelling framework, such as STEM, can be a valuable tool for the
      scientific community and provide a collaborative platform for developing such
      models.

PMID- 22988978
TI  - The cross-talk between the skeleton and energy metabolism.

PMID- 22988977
TI  - The strain-specific dynamics of Escherichia coli O157:H7 faecal shedding in
      cattle post inoculation.
AB  - This study reports analysis of faecal shedding dynamics in cattle for three
      Escherichia coli O157:H7 (ECO157) strains (S1, S2 and S3) of different genotype
      and ecological history, using experimental inoculation data. The three strains
      were compared for their shedding frequency and level of ECO157 in faeces. A
      multistate Markov chain model was used to compare shedding patterns of S1 and S2.
      Strains S1 and S2 were detected seven to eight times more often and at 10(4)
      larger levels than strain S3. Strains S1 and S2 had similar frequencies and
      levels of shedding. However, the total time spent in the shedding state during
      colonization was on average four times longer for S1 (15 days) compared to S2 (4
      days). These results indicate that an ECO157 strain effect on the frequency,
      level, pattern and the duration of faecal shedding may need to be considered in
      control of ECO157 in the cattle reservoir.

PMID- 22988979
TI  - Effect of acid swallowing on esophageal contraction in patients with heartburn
      related to hypersensitivity.
AB  - BACKGROUND AND AIM: There are heterogeneous subgroups among those with heartburn,
      and data on these individuals are relatively scant. We aimed to evaluate the
      effect of acid challenge on the segmental contractions of esophageal smooth
      muscle in endoscopy-negative patients with normal esophageal acid exposure.
      METHODS: High-resolution esophageal manometry (HRM) was performed on 30 endoscopy
      negative patients with heartburn accompanied by normal esophageal acid exposure
      using 10 water swallows followed by 10 acidic pomegranate juice swallows.
      Patients were classified into functional heartburn (FH) and hypersensitive
      esophagus (HE) groups based on the results of 24-hr impedance pH testing. HRM
      topographic plots were analyzed and maximal wave amplitude and pressure volumes
      were measured for proximal and distal smooth muscle segments. RESULTS: The
      pressure volume of the distal smooth muscle segment in the HE group measured
      during acidic swallows was higher than during water swallows (2224.1 +/- 68.2
      mmHg/cm per s versus 2105.6 +/- 66.4 mmHg/cm per s, P = 0.027). A prominent shift
      in the pressure volume to the distal smooth muscle segment was observed in the HE
      group compared with the FH group (segmental ratio: 2.72 +/- 0.08 versus 2.39 +/-
      0.07, P = 0.005). Manometric measurements during acidic swallows revealed that
      this shift was augmented in the HE group. The optimal ratio of pomegranate juice
      swallowing for discrimination of FH from HE was 2.82, with a sensitivity of 88.9%
      and a specificity of 100%. CONCLUSIONS: Hypercontractile response of distal
      smooth muscle segment to acid swallowing was more prominent in the HE group than
      the FH group.

PMID- 22988976
TI  - An efficient RNA interference screening strategy for gene functional analysis.
AB  - BACKGROUND: RNA interference (RNAi) is commonly applied in genome-scale gene
      functional screens. However, a one-on-one RNAi analysis that targets each gene is
      cost-ineffective and laborious. Previous studies have indicated that siRNAs can
      also affect RNAs that are near-perfectly complementary, and this phenomenon has
      been termed an off-target effect. This phenomenon implies that it is possible to
      silence several genes simultaneously with a carefully designed siRNA. RESULTS: We
      propose a strategy that is combined with a heuristic algorithm to design suitable
      siRNAs that can target multiple genes and a group testing method that would
      reduce the number of required RNAi experiments in a large-scale RNAi analysis. To
      verify the efficacy of our strategy, we used the Orchid expressed sequence tag
      data as a case study to screen the putative transcription factors that are
      involved in plant disease responses. According to our computation, 94 qualified
      siRNAs were sufficient to examine all of the predicated 229 transcription
      factors. In addition, among the 94 computer-designed siRNAs, an siRNA that
      targets both TF15 (a previously identified transcription factor that is involved
      in the plant disease-response pathway) and TF21 was introduced into orchids. The
      experimental results showed that this siRNA can simultaneously silence TF15 and
      TF21, and application of our strategy successfully confirmed that TF15 is
      involved in plant defense responses. Interestingly, our second-round analysis,
      which used an siRNA specific to TF21, indicated that TF21 is a previously
      unidentified transcription factor that is related to plant defense responses.
      CONCLUSIONS: Our computational results showed that it is possible to screen all
      genes with fewer experiments than would be required for the traditional one-on
      one RNAi screening. We also verified that our strategy is capable of identifying
      genes that are involved in a specific phenotype.

PMID- 22988980
TI  - An electrochemical capacitor electrode based on porous carbon spheres hybrided
      with polyaniline and nanoscale ruthenium oxide.
AB  - Nanoscopic ruthenium oxide (RuO(2))/polyaniline (PANI)/carbon double-shelled
      hollow spheres (CS) composites, RuO(2)/PANI/CS, have been prepared via electro
      polymerization of aniline and redox deposition of RuO(2) on the surface of CS.
      The structures and morphologies of the resulting ternary composites are
      characterized using scanning electron microscopy (SEM), infrared spectroscopy
      (IR), energy-dispersive X-ray spectroscopy (EDX). The electrochemical properties
      of the ternary composites as active electrode materials for electrochemical
      capacitors have been investigated by different electrochemical techniques
      including cyclic voltammetry, galvanostatic charge-discharge, and impedance
      spectroscopy. The results show that the specific capacitance of RuO(2)/PANI/CS
      composites is 531 F g(-1) at 1 mA cm(-2) in 1.0 M H(2)SO(4) electrolyte, which is
      higher than many other currently available ternary composites based on
      RuO(2)/PANI. At the same time, the composites display a good rate capability and
      70% of the initial specific capacitance is retained with the charge-discharge
      current density up to 10 mA cm(-2).

PMID- 22988981
TI  - Synthesis of thieno-bridged porphyrins: changing the antiaromatic contribution by
      the direction of the thiophene ring.
AB  - Two types of thieno-bridged porphyrins were synthesized by incorporating a
      thiophene group across their meso and beta positions with different directions of
      the thiophene ring to investigate the aromaticity of these porphyrins with
      extended pi-systems. The 2,3-thieno-bridged porphyrin showed a larger
      antiaromatic contribution than did the 3,4-thieno-bridged porphyrin. In the
      former, the antiaromatic contribution is based on a 20-pi-electron conjugated
      circuit. The two thieno-bridged porphyrins were characterized by calculations of
      nucleus-independent chemical shift and anisotropy of the induced current density
      as well as by X-ray crystallography, NMR spectroscopy, UV-vis-NIR absorption
      spectroscopy, electrochemical studies, time-resolved excited-state analysis, and
      two-photon absorption cross section measurements. Chemical derivatization of the
      2,3-thieno-bridged porphyrin was also demonstrated.

PMID- 22988982
TI  - Fourier transform infrared and Raman and surface-enhanced Raman spectroscopy
      studies of a novel group of boron analogues of aminophosphonic acids.
AB  - Five analogues of a novel group of boron derivatives of aminophosphonic acids-N
      benzylamino-(3-boronphenyl)-S-methylphosphonic acid (m-PhS), N-benzylamino-(4
      boronphenyl)-S-methylphosphonic acid (p-PhS), N-benzylamino-(2-boronphenyl)-R
      methylphosphonic acid (o-PhR), N-benzylamino-(3-boronphenyl)-R-methylphosphonic
      acid (m-PhR), and N-benzylamino-(4-boronphenyl)-R-methylphosphonic acid (p-PhR)
      were studied using Fourier transform infrared (FT IR), Fourier transform Raman
      (FT RS), and surface-enhanced Raman (SERS) spectroscopies. Analysis of obtained
      FT IR and FT RS spectra show that all investigated compounds in the solid state
      exist as dimeric species formed by an H-bonding interaction between -B(OH)(2)
      moieties of each monomer. In addition, comparison of the wavenumbers,
      intensities, and broadness of bands from the FT Raman and SERS spectra allowed
      information to be obtained regarding the adsorption geometry of the investigated
      compounds immobilized onto an electrochemically roughened silver substrate.

PMID- 22988983
TI  - Retrospective review of trends in assaults and seclusion at an acute psychiatric
      ward over a 5-year period.
AB  - In developing countries such as South Africa, not much is known about the
      prevalence of assaults and seclusion occurring in mental health wards over time.
      Here, we describe a 5-year trend in assaults and seclusions, stratified by
      gender, at Stikland Hospital, South Africa. A retrospective review of clinical
      records of patients admitted to the acute psychiatric admission wards at Stikland
      and involved in assault and secluded was undertaken between 1 January 2005 and 31
      December 2010. Data on the number of patient and staff assaults as well as
      seclusions, gender, age, marital status, level of education, level of income,
      duration of hospital admission and primary psychiatric diagnosis were collected.
      Significantly (P < 0.01) more men than women engaged in patient assaults, while
      significantly (P < 0.01) more men were secluded than women. On a monthly basis,
      the number of gender-stratified patient assaults and seclusions significantly
      increased (P < 0.01) throughout the study period. In conclusion, we show here
      that gender had a significant effect on both patient assault and seclusion
      numbers, which increased towards the end of the study period. Monitoring of these
      events is therefore important to continuously improve quality of care.

PMID- 22988984
TI  - Influence of the molecular design on the antifouling performance of poly(ethylene
      glycol) monolayers grafted on (111) Si.
AB  - Various poly(ethylene glycol) monomethyl ether moieties were grafted onto
      hydrogenated silicon surfaces in order to investigate the influence of the
      molecular design on the antifouling performance of such coatings. The grafted
      chains were either oligo(ethylene oxide) chains (EG)(n)OMe bound to silicon via
      Si-O-C covalent bonds, or hybrid alkyl/oligo(ethylene oxide) chains
      C(p)(EG)(n)OMe bound via Si-C covalent bonds (from home-synthesized precursors).
      Quantitative IR spectroscopy gave the molecular coverage of the grafted layers,
      and AFM imaging demonstrated that a proper surfactinated rinse yields
      C(p)(EG)(n)OMe layers free of unwanted residues. The protein-repellent character
      of these grafted layers (here, toward BSA) was studied by IR and AFM imaging.
      C(p)(EG)(n)OMe layers exhibit a lower surface concentration than (EG)(n)OMe
      layers, because of the presence of a solvent in the grafting solution; they
      however demonstrate high resistance against BSA adsorption for high values of the
      n/p ratio and a higher stability than (EG)(n)OMe. This behavior is consistently
      explained by the poor ordering capability of the alkyl part of the layer,
      contrary to what is observed for similar layers on Au, and the key role of an
      entangled arrangement of the ethylene oxide chains which forms when these chains
      are long enough.

PMID- 22988985
TI  - Fatal outcome after heart transplantation caused by Aspergillus lentulus.
AB  - Opportunistic invasive fungal infections are a major cause of mortality in
      immunocompromised patients. Early diagnosis of invasive aspergillosis and proper
      identification of the causative agent is crucial for guidance of therapy.
      Accurate differentiation of Aspergillus lentulus, a filamentous fungus often
      misidentified as atypical Aspergillus fumigatus, is of concern as multiple
      antifungal drugs show a reduced susceptibility. This is the first report, to our
      knowledge, of a proven pulmonary invasive fungal infection caused by A. lentulus
      after heart transplantation.

PMID- 22988987
TI  - Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies.
AB  - The receptor tyrosine kinase ROR1 has been shown to be overexpressed in chronic
      lymphocytic leukemia (CLL). The aim of this study was to further characterize the
      expression of ROR1 and the other member of the ROR family, ROR2, in other
      lymphoid and myeloid malignancies. Normal white blood cells and reactive lymph
      nodes were negative for ROR1 and ROR2. A significantly high and uniform surface
      expression of ROR1 was found in CLL/hairy cell leukemia (HCL) compared to mantle
      cell lymphoma (MCL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma
      (DLBCL), follicular lymphoma (FL), myelomas, acute lymphoblastic leukemia (ALL)
      and myeloid leukemias (p = 0.02 to < 0.001). The lowest proportion of ROR1+ cells
      was seen in FL, whereas CLL, HCL and CML had significantly higher numbers of
      ROR1+ cells. Longitudinal follow-up of individual patients with CLL revealed that
      ROR1+ cells remained stable over time in non-progressive patients, but increased
      when the disease progressed (p < 0.05). Thus, a variable staining pattern of ROR1
      ranging from very high (CLL, HCL) and high (CML) to intermediate (myeloma and
      DLBCL) or low (FL) was noted. ROR2 was not detected in hematological
      malignancies.

PMID- 22988986
TI  - Treatment patterns in major depressive disorder after an inadequate response to
      first-line antidepressant treatment.
AB  - BACKGROUND: The aim of the study was to determine the most common pharmacological
      strategies used in the management of major depressive disorder (MDD) after an
      inadequate response to first-line antidepressant treatment in clinical practice.
      METHODS: Multicenter, non-interventional study in adult outpatients with a DSM-IV
      TR diagnosis of MDD and inadequate response to first-line antidepressant
      medication. Multiple logistic regression analyses were performed to identify
      independent factors associated with the adoption of a specific second-line
      strategy. RESULTS: A total of 273 patients were analyzed (mean age: 46.8 years,
      67.8% female). Baseline mean Montgomery-Asberg Depression Rating Scale total
      score was 32.1 (95%CI 31.2-32.9). The most common strategies were: switching
      antidepressant medication (39.6%), augmentation (18.8%), and combination therapy
      (17.9%). Atypical antipsychotic drugs were the most commonly used agent for
      augmenting antidepressant effect. The presence of psychotic symptoms and the
      number of previous major depressive episodes were associated with the adoption of
      augmenting strategy (OR = 3.2 and 1.2, respectively). CONCLUSION: The switch to
      another antidepressant agent was the most common second-line therapeutic
      approach. Psychiatrists chose augmentation based on a worse patients' clinical
      profile (number of previous episodes and presence of psychotic symptoms).

PMID- 22988988
TI  - Internet use and anxiety in people with melanoma and nonmelanoma skin cancer.
AB  - BACKGROUND: People with cancer are increasingly turning to the Internet for
      health-related information. OBJECTIVE: To compare the patterns of Internet use of
      people with skin cancer with previous findings by including people with
      nonmelanoma skin cancer (NMSC) using a comprehensive survey. To evaluate
      perceived anxiety levels and overall satisfaction after searching the Internet of
      people with skin cancer. METHODS & MATERIALS: We conducted a survey study and
      prospectively collected data from people newly diagnosed with melanoma or NMSC.
      RESULTS: Four hundred fifteen participants with melanoma and 400 with NMSC
      completed the questionnaire. Internet use and overall satisfaction with the
      Internet search increased more than 50% in participants with melanoma from 2005.
      One-third of participants with melanoma, but many fewer participants with NMSC,
      reported higher anxiety after Internet use. Participants who were younger,
      female, more highly educated, and diagnosed with melanoma were most likely to use
      the Internet to search for information about their diagnosis. CONCLUSION:
      Internet use is prevalent and increasing sharply in individuals with skin cancer.
      The majority of individuals describe their use of the Internet as a positive
      experience. Greater anxiety from searching the Internet is more common in
      individuals with melanoma than in those with NMSC.

PMID- 22988989
TI  - Alexandrite laser for the treatment of port wine stains refractory to pulsed dye
      laser.
AB  - BACKGROUND: The 755-nm ms pulsed Alexandrite laser (MSPAL) has been reported to
      be successfully in the treatment of port wine stains (PWS) that are refractory to
      pulsed dye laser (PDL). MATERIALS & METHODS: This was a prospective pilot study
      to assess the degree of improvement after a series of treatments with a MSPAL for
      hypertrophic, nodular, and macular PWS refractory to PDL. Treatment was
      administered to the PWS using the 755-nm MSPAL at settings of 3-ms pulse
      duration, 8- to 12-mm spot, 40 to 60 J/cm(2), and dynamic cooling of 60/40.
      Patients received a series of two to four treatment session, given at 6- to 8
      week intervals. RESULTS: The eight patients in this study had undergone a mean of
      25.9 treatment sessions with PDL over 8.8 years. The number of MSPAL sessions
      required for significant improvement of PWS ranged from two to four (mean 2.6).
      From before treatment to 2 months after treatment, the mean score decreased from
      3.2 to 1.4 for skin color (56.3% mean improvement, 95% confidence interval
      (CI)=53.2-59.4%), from 2.5 to 1.0 at (60.0% mean improvement, 95% CI=55.9-64.1%)
      for skin texture, and from 3.2 to 1.3 (59.4% mean improvement, 95% CI=56.2-62.6%)
      for overall cosmetic outcome (all p<.05). DISCUSSION: In this pilot study, PDL
      resistant PWS responded significantly to a series of MSPAL treatments. Given the
      potential for adverse effects and narrow therapeutic index, treatment with
      conservative parameters and close observation of tissue response are essential.

PMID- 22988990
TI  - Fractionated carbon dioxide laser treatment of photoaging: prospective study in
      45 patients and review of the literature.
AB  - BACKGROUND: Ablative fractional photothermolysis (AFP) has been reported to be
      effective for photoaging. OBJECTIVE: To perform a clinical trial in 45 patients
      with moderate to severe skin photoaging to quantify improvement with AFP.
      MATERIALS AND METHODS: A prospective, single-blind study in 45 patients who
      presented for desired treatment of photoaging. Patients received a series of two
      to three treatments with AFP. RESULTS: Thirty-nine women (86.7%) and six men
      (13.3%) were enrolled. Patients received two or three treatment sessions (mean
      2.4). There were no incidence of adverse events of scarring, prolonged erythema
      (lasting more than 7 days), postinflammatory hyper- or hypopigmentation, or
      infection in the 108 treatment sessions given during this study. Mean improvement
      was 48.5% (95% confidence interval (CI)=44.6-52.4%) for skin texture, 50.3% (95%
      CI=46.1-54.5%) for skin laxity, 53.9% (95% CI=49.5-58.5%) for dyschromia, and
      52.4% (95% CI=47.9-56.9%) for overall cosmetic outcome (all p<.05). CONCLUSIONS:
      Significant improvement in photoaging of the face can be achieved using an AFP
      device with skin types I to III after a series of two to three treatments.

PMID- 22988991
TI  - The efficacy of stereoimage optical topometry to evaluate depressed acne scar
      treatment using cultured autologous fibroblast injection.

PMID- 22988992
TI  - Commentary on Micropunch (0.8 mm or less in diameter) hair transplantation.

PMID- 22988993
TI  - Hair transplantation for reconstruction of scalp defects using artificial dermis.

PMID- 22988994
TI  - Reply to: Use of reflectance confocal microscopy to differentiate hidrocystoma
      from basal cell carcinoma.

PMID- 22988995
TI  - A patient with Bowen's disease successfully treated using a 1,927-nm thulium
      fiber fractional laser.

PMID- 22988996
TI  - Treatment of lipomas using a subdermal 1,444-nm micropulsed neodymium-doped
      yttrium aluminum garnet laser.

PMID- 22988997
TI  - Tandem repeats modify the structure of the canine CD1D gene.
AB  - Among the CD1 proteins that present lipid antigens to T cells, CD1d is the only
      one that stimulates a population of T cells with an invariant T-cell receptor
      known as NKT cells. Sequencing of a 722 nucleotide gap in the dog (Canis lupus
      familiaris) genome revealed that the canine CD1D gene lacks a sequence homologous
      to exon 2 of human CD1D, coding for the start codon and signal peptide. Also, the
      canine CD1D gene contains three different short tandem repeats that disrupt the
      expected gene structure. Because canine CD1D cDNA lacks sequences homologous to
      human exon 2 and 3, the functionality of canine CD1d protein may be affected, and
      this could have consequences for the development and activation of canine NKT
      cells.

PMID- 22988998
TI  - Molecular typing of Coxiella burnetii from animal and environmental matrices
      during Q fever epidemics in the Netherlands.
AB  - BACKGROUND: The bacterium Coxiella burnetii has caused unprecedented outbreaks of
      Q fever in the Netherlands between 2007 and 2010. Since 2007, over 4000 human
      cases have been reported, with 2354 cases in 2009 alone. Dairy goat farms were
      identified as most probable sources for emerging clusters of human Q fever cases
      in their vicinity. However, identifying individual farms as primary source for
      specific clusters of human cases remains a challenge, partly due to limited
      knowledge of the different C. burnetii strains circulating in livestock, the
      environment and humans. RESULTS: We used a multiplex multi-locus variable number
      of tandem repeats analysis (MLVA) assay to investigate the genotypic diversity of
      C. burnetii in different types of samples that were collected nationwide during
      the Dutch Q fever outbreaks between 2007 and 2010. Typing was performed on C.
      burnetii positive samples obtained from several independent studies investigating
      C. burnetii presence in animals and the environment. Six different genotypes were
      identified on 45 farm locations, based on sequence-confirmed estimates of repeat
      numbers of six MLVA markers. MLVA genotype A was observed on 38 of the 45
      selected farm locations in animals and in environmental samples. CONCLUSIONS:
      Sequence confirmation of the numbers of tandem repeats within each locus and
      consensus about repeat identification is essential for accurate MLVA typing of C.
      burnetii. MLVA genotype A is the most common genotype in animal samples obtained
      from goat, sheep, and rats, as well as in environmental samples such as
      (aerosolized) dust, which is considered to be the major transmission route from
      animals via the environment to humans. The finding of a single dominant MLVA
      genotype in patients, the environment, and livestock complicates accurate source
      finding. Pinpointing individual sources in the Netherlands requires
      discrimination of genotypes at a higher resolution than attained by using MLVA,
      as it is likely that the dominant C. burnetii MLVA type will be detected on
      several farms and in different patients in a particular area of interest.

PMID- 22989000
TI  - A two-question method for assessing gender categories in the social and medical
      sciences.
AB  - Three studies (N = 990) assessed the statistical reliability of two methods of
      determining gender identity that can capture transgender spectrum identities
      (i.e., current gender identities different from birth-assigned gender
      categories). Study 1 evaluated a single question with four response options
      (female, male, transgender, other) on university students. The missing data rate
      was higher than the valid response rates for transgender and other options using
      this method. Study 2 evaluated a method of asking two separate questions (i.e.,
      one for current identity and another for birth-assigned category), with response
      options specific to each. Results showed no missing data and two times the
      transgender spectrum response rate compared to Study 1. Study 3 showed that the
      two-question method also worked in community samples, producing near-zero missing
      data. The two-question method also identified cisgender identities (same birth
      assigned and current gender identity), making it a dynamic and desirable
      measurement tool for the social and medical sciences. 

PMID- 22988999
TI  - A longitudinal study of patients' symptoms before and during the first year after
      lung transplantation.
AB  - BACKGROUND: Lung transplantation provides a viable option for survival of end
      stage respiratory disease. In addition to prolonging survival, there is
      considerable interest in improving patient-related outcomes such as transplant
      recipients' symptom experiences. METHODS: A prospective, repeated measures design
      was used to describe the symptom experience of 85 lung transplant recipients
      between 2000 and 2005. The transplant symptom inventory was administered before
      and at one, three, six, nine, and 12 months post-transplant. Ridit analysis
      provided a unique method for describing symptom experiences and changes. RESULTS:
      After lung transplantation, significant (p<0.05) improvements were reported for
      the most frequently occurring and most distressing pre-transplant symptoms (e.g.,
      shortness of breath with activity). Marked increases in the frequency and
      distress of new symptoms such as tremors were also reported. Patterns of symptom
      frequency and distress varied with time since transplant. CONCLUSION: The
      findings provide data-based information that can be used to inform pre- and post
      transplant patient education and also help caregivers anticipate a general time
      frame for symptom changes to prevent or minimize symptoms and their associated
      distress. In addition, symptoms are described, using an innovative method of
      illustration which shows "at-a-glance" change or lack of change in patients'
      symptoms from pre- to post-lung transplant.

PMID- 22989001
TI  - Biologically relevant heterodinuclear iron-manganese complexes.
AB  - The heterodinuclear complexes [Fe(III)Mn(II)(L-Bn)(MU-OAc)(2)](ClO(4))(2) (1) and
      [Fe(II)Mn(II)(L-Bn)(MU-OAc)(2)](ClO(4)) (2) with the unsymmetrical dinucleating
      ligand HL-Bn {[2-bis[(2-pyridylmethyl)aminomethyl]]-6-[benzyl-2
      (pyridylmethyl)aminomethyl]-4-methylphenol} were synthesized and characterized as
      biologically relevant models of the new Fe/Mn class of nonheme enzymes.
      Crystallographic studies have been completed on compound 1 and reveal an
      Fe(III)Mn(II)MU-phenoxobis(MU-carboxylato) core. A single location of the Fe(III)
      ion in 1 and of the Fe(II) ion in 2 was demonstrated by Mossbauer and (1)H NMR
      spectroscopies, respectively. An investigation of the temperature dependence of
      the magnetic susceptibility of 1 revealed a moderate antiferromagnetic
      interaction (J = 20 cm(-1)) between the high-spin Fe(III) and Mn(II) ions in 1,
      which was confirmed by Mossbauer and electron paramagnetic resonance (EPR)
      studies. The electrochemical properties of complex 1 are described. A
      quasireversible electron transfer at -40 mV versus Ag/AgCl corresponding to the
      Fe(III)Mn(II)/Fe(II)Mn(II) couple appears in the cyclic voltammogram. Thorough
      investigations of the Mossbauer and EPR signatures of complex 2 were performed.
      The analysis allowed evidencing of a weak antiferromagnetic interaction (J = 5.72
      cm(-1)) within the Fe(II)Mn(II) pair consistent with that deduced from magnetic
      susceptibility measurements (J = 6.8 cm(-1)). Owing to the similar value of the
      Fe(II) zero-field splitting (D(Fe) = 3.55 cm(-1)), the usual treatment within the
      strong exchange limit was precluded and a full analysis of the electronic
      structure of the ground state of complex 2 was developed. This situation is
      reminiscent of that found in many diiron and iron-manganese enzyme active sites.

PMID- 22989002
TI  - Influence of the length of imogolite-like nanotubes on their cytotoxicity and
      genotoxicity toward human dermal cells.
AB  - Physical-chemical parameters such as purity, structure, chemistry, length, and
      aspect ratio of nanoparticles (NPs) are linked to their toxicity. Here, synthetic
      imogolite-like nanotubes with a set chemical composition but various sizes and
      shapes were used as models to investigate the influence of these physical
      parameters on the cyto- and genotoxicity and cellular uptake of NPs. The NPs were
      characterized using X-ray diffraction (XRD), small angle X-ray scattering (SAXS),
      and atomic force microscopy (AFM). Imogolite precursors (PR, ca. 5 nm curved
      platelets), as well as short tubes (ST, ca. 6 nm) and long tubes (LT, ca. 50 nm),
      remained stable in the cell culture medium. Internalization into human
      fibroblasts was observed only for the small particles PR and ST. None of the
      tested particles induced a significant cytotoxicity up to a concentration of 10(
      1) mg.mL(-1). However, small sized NPs (PR and ST) were found to be genotoxic at
      very low concentration 10(-6) mg.mL(-1), while LT particles exhibited a weak
      genotoxicity. Our results indicate that small size NPs (PR, ST) were able to
      induce primary lesions of DNA at very low concentrations and that this DNA damage
      was exclusively induced by oxidative stress. The higher aspect ratio LT particles
      exhibited a weaker genotoxicity, where oxidative stress is a minor factor, and
      the likely involvement of other mechanisms. Moreover, a relationship among cell
      uptake, particle aspect ratio, and DNA damage of NPs was observed.

PMID- 22989003
TI  - Influence of translation on RppH-dependent mRNA degradation in Escherichia coli.
AB  - In Escherichia coli, the endonuclease RNase E can access internal cleavage sites
      in mRNA either directly or by a 5' end-dependent mechanism in which cleavage is
      facilitated by prior RppH-catalysed conversion of the 5'-terminal triphosphate to
      a monophosphate, to which RNase E can bind. The characteristics of transcripts
      that determine which of these two pathways is primarily responsible for their
      decay are poorly understood. Here we report the influence of ribosome binding and
      translocation on each pathway, using yeiP and trxB as model transcripts. Ribosome
      binding to the translation initiation site impedes degradation by both
      mechanisms. However, because the effect on the rate of 5' end-independent decay
      is greater, poor ribosome binding favours degradation by that pathway. Arresting
      translation elongation with chloramphenicol quickly inhibits RNase E cleavage
      downstream of the initiation codon but has little or no immediate effect on
      cleavage upstream of the ribosome binding site. RNase E binding to a
      monophosphorylated 5' end appears to increase the likelihood of cleavage at sites
      within the 5' untranslated region. These findings indicate that ribosome binding
      and translocation can have a major impact on 5' end-dependent mRNA degradation in
      E. coli and suggest a possible sequence of events that follow pyrophosphate
      removal.

PMID- 22989004
TI  - Deep sequencing does not reveal additional transmitted mutations in patients
      diagnosed with HIV-1 variants with single nucleoside reverse transcriptase
      inhibitor resistance mutations.
AB  - OBJECTIVES: The aim of the study was to gain more insight into the relationship
      between transmitted singletons found at HIV diagnosis by population sequencing
      and the possible presence of clinically relevant viral minorities containing
      additional resistance mutations. METHODS: We studied the viral quasispecies and
      therapy response in 10 individuals with transmitted single nucleoside reverse
      transcriptase inhibitor (NRTI)-related resistance mutations as detected by
      population sequencing. RESULTS: Ultra-deep pyrosequencing did not reveal
      additional drug-resistance mutations in nine of 10 patients. In these nine
      patients, no breakthrough with resistant viruses was observed despite the use of
      low genetic nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens
      in the majority of patients. CONCLUSIONS: These data suggest that viral minority
      variants containing additional resistance mutations may be rare in patients with
      transmitted NRTI singletons in the Netherlands. Larger studies are required to
      confirm these findings and to determine the therapeutic consequences.

PMID- 22989005
TI  - Biocompatible silicon surfaces through orthogonal click chemistries and a high
      affinity silicon oxide binding peptide.
AB  - Multifunctionality is gaining more and more importance in the field of improved
      biomaterials. Especially peptides feature a broad chemical variability and are
      versatile mediators between inorganic surfaces and living cells. Here, we
      synthesized a unique peptide that binds to SiO(2) with nM affinity. We equipped
      the peptide with the bioactive integrin binding c[RGDfK]-ligand and a fluorescent
      probe by stepwise Diels-Alder reaction with inverse electron demand and copper(I)
      catalyzed azide-alkyne cycloaddition. For the first time, we report the
      generation of a multifunctional peptide by combining these innovative coupling
      reactions. The resulting peptide displayed an outstanding binding to silicon
      oxide and induced a significant increase in cell spreading and cell viability of
      osteoblasts on the oxidized silicon surface.

PMID- 22989006
TI  - No association between neuropathy and restless legs in Parkinson's disease.
AB  - BACKGROUND: The prevalence of restless legs syndrome (RLS) has been studied
      extensively in Parkinson's disease (PD), with conflicting findings. More
      recently, both neuropathy and leg motor restlessness (LMR) have been found to be
      significantly more prevalent in PD patients than in controls. AIMS: Our objective
      was to determine whether RLS or LMR may be secondary to neuropathy, or its
      currently postulated determinants, cumulative levodopa usage and vitamin B(12)
      metabolism, in patients with PD. MATERIALS AND METHODS: We compared prevalence of
      RLS, LMR and neuropathy in 37 PD patients and 37 age- and gender-matched
      controls. Correlations between RLS/LMR and neuropathy and symptomatic neuropathy,
      cumulative levodopa usage and vitamin B(12) levels were ascertained. RESULTS: RLS
      prevalence was comparable in PD patients and controls (16.2% vs 10.8%; P = 0.30).
      LMR was significantly more common in PD patients than in controls (40.5% vs
      16.2%; P = 0.038), as was neuropathy (37.8% vs 8.1%; P = 0.005). Neither RLS, nor
      LMR correlated with neuropathy or symptomatic neuropathy, cumulative levodopa
      exposure or serum vitamin B(12) levels in patients with PD. There was a non
      significant trend for a correlation between LMR and earlier age of onset of PD (P
      = 0.069). CONCLUSIONS: RLS and LMR appear unrelated to neuropathy or symptomatic
      neuropathy, cumulative levodopa usage, or serum vitamin B(12) levels in patients
      with PD. The occurrence of LMR may relate to the earlier onset of PD, raising the
      possibility of common pathophysiological mechanisms for PD and RLS, of which LMR
      may be an early manifestation in some patients.

PMID- 22989007
TI  - The development of insecticide-treated durable wall lining for malaria control:
      insights from rural and urban populations in Angola and Nigeria.
AB  - BACKGROUND: Durable lining (DL) is a deltamethrin-impregnated polyethylene
      material, which is designed to cover domestic walls that would normally be
      sprayed with residual insecticide. The operational success of DL as a long
      lasting insecticidal substrate will be dependent on a high level of user
      acceptability as households must maintain correctly installed linings on their
      walls for several years. Preliminary trials were undertaken to identify a
      material to develop into a marketable wall lining and to assess its level of
      acceptability among rural and urban populations. METHODS: In Angola (n=60),
      prototype DL and insecticide-treated plastic sheeting (ITPS) were installed on
      urban house walls and ceilings, respectively, and acceptability was compared to
      indoor residual spraying (IRS) (n=20) using a knowledge, attitude and practice
      (KAP) questionnaire. In Nigeria (n=178), three materials (prototype DL, ITPS and
      insecticide-treated wall netting) were distributed among rural and urban
      households. User opinions were gathered from focus group discussions, in-depth
      interviews and KAP questionnaires. RESULTS: In Angola, after two weeks, the
      majority of participants (98%) expressed satisfaction with the products and
      identified the killing of insects as the materials' principal benefits (73%).
      After one year, despite a loss of almost 50% of households to refugee
      repatriation, all 32 remaining households still asserted that they had liked the
      DL/ITPS in their homes and given the choice of intervention preferred DL/ITPS to
      IRS (94%) or insecticide-treated nets (78%). In Nigeria, a dichotomy between
      rural and urban respondents emerged. Rural participants favoured wall adornments
      and accepted wall linings because of their perceived decorative value and
      entomological efficacy. By contrast, urban households preferred minimal wall
      decoration and rejected the materials based upon objections to their aesthetics
      and installation feasibility. CONCLUSIONS: The high level of acceptability among
      rural inhabitants in Nigeria identifies these communities as the ideal target
      consumer group for durable wall linings. The poorer compliance among urban
      participants suggests that wall linings would not be readily adopted or sustained
      in these regions. If DL is as well received by other rural populations it could
      overcome some of the logistical constraints associated with spray campaigns and
      has the potential to become a long-lasting alternative to IRS in malaria endemic
      areas.

PMID- 22989008
TI  - Lactase persistence/non-persistence genetic variants in irritable bowel syndrome
      in an endemic area for lactose malabsorption.
AB  - BACKGROUND AND AIM: Lactase non-persistence is common in India. We evaluated: (i)
      frequency of lactase gene (C/T-13910 and G/A-22018) polymorphisms in irritable
      bowel syndrome (IBS) and healthy controls (HC), (ii) association between these
      polymorphisms and IBS-subtypes and symptoms. METHODS: A total of 150 IBS patients
      (Rome-III criteria) and 252 age and gender-matched HC were evaluated for C/T
      13910 and G/A-22018 genotypes using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: Totals of 79 (52%), 52 (35%)
      and 19 (13%) patients had diarrhea-predominant IBS (D-IBS), constipation
      predominant IBS (C-IBS) and alternating diarrhea and constipation IBS (A-IBS),
      respectively (Rome-III). Frequency of C/T-13910 [genotypes: CC 102 (68%), CT 43
      (29%), TT 5 (3%) vs CC 155 (61%), CT 83 (33%), TT 14 (6%), P > 0.05] and G/A
      22018 [GG 97 (65%), GA 41 (27%), AA 12 (8%) vs GG 154 (61%), GA 78 (31%), AA 20
      (8%), P > 0.05] were similar among IBS and HC. Patients with D-IBS more often had
      C/T-13910 and G/A-22018 genotypes than C-IBS (CC 71 [90%], CT 6 [8%], TT 2 [2%])
      versus (24 [46%], 25 [48%], 3 [6%]), A-IBS (7 [39%], 12 [63%], 0, [0%]) and HC
      (155 [61%], 83 [33%], 14 [6%]), P < 0.0001 and (GG 69 [87%], GA 6 [8%], AA 4
      [5%]) vs (22 [42%], 24 [46%], 6 [12%]) vs (6 [32%], 11 [58%], 2 [10%]), P <
      0.0001. IBS with CC and GG genotypes more often had abdominal pain (P = 0.005),
      distension (P = 0.031) and higher stool frequency (P = 0.003) and reported
      symptoms following dairy products than non-CC (P < 0.0001). CONCLUSION: Though
      C/T-13910 and G/A-22018 polymorphisms were comparable among IBS and HC, these
      were more common among D-IBS and reported some symptoms like abdominal pain,
      bloating and exacerbation by dairy products.

PMID- 22989010
TI  - Identifying causes for poor visual outcome after DSEK/DSAEK following secondary
      DMEK in the same eye.
AB  - PURPOSE: To identify causes of reduced visual acuity after Descemet stripping
      (automated) endothelial keratoplasty (DSEK/DSAEK) and to determine whether such
      eyes can be successfully 'repaired' with a secondary Descemet membrane
      endothelial keratoplasty (DMEK). METHODS: Twelve eyes of 12 patients, who
      underwent secondary DMEK to manage poor visual outcome after initial DSEK/DSAEK,
      were evaluated with biomicroscopy, Pentacam imaging, and specular and confocal
      microscopy, before and at 1, 3 and 6 months after DMEK. RESULTS: Four causes of
      reduced optical quality of the transplanted host cornea could be identified in
      DSEK/DSAEK: five eyes (42%) showed large host-Descemet remnants within the visual
      axis during surgery; six eyes (50%) irregular graft thickness; six eyes subtle
      'stromal waves'; and nine eyes (75%) high reflectivity at the donor-to-host
      interface. After DMEK graft replacement, all corneas cleared and achieved a best
      corrected visual acuity of >=20/25 (>=0.8), except for one with a partial
      Descemet graft detachment. Pachymetry values decreased from 670 (+/-112) MUm
      before to 517 (+/-57) MUm after secondary DMEK. Higher-order aberrations (Coma
      and Trefoil) at the posterior surface tended to be lower (p = 0.07) in DMEK
      grafts than in DSEK/DSAEK grafts. CONCLUSION: Host-Descemet remnants at the donor
      to-host interface, interface reflectivity, graft thickness irregularity and donor
      stromal contraction may contribute to poor visual outcome after DSEK/DSAEK,
      without causing permanent host corneal damage, as in most cases, complete visual
      recovery could be achieved by performing a secondary DMEK.

PMID- 22989009
TI  - HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline),
      regulates p53 through enhanced HDM2 autoubiquitination and degradation in human
      malignant B-cell lymphomas.
AB  - BACKGROUND: Lymphomas frequently retain wild-type (wt) p53 function but
      overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a
      suitable model for studying the therapeutic value of disrupting the HDM2-p53
      interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are
      under various stages of preclinical and clinical investigation. Previously, we
      examined the anti-lymphoma activity of MI-319, the laboratory grade of a new
      class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI
      219, the clinical grade has become readily available. This study further examines
      the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma
      cell lines as well as a cohort of patient-derived B-lymphocytes for its potential
      clinical use. RESULTS: Preclinical assessment of MI-219 was evaluated by means of
      an in vitro and ex vivo approach and compared to Nutlin-3, the gold standard.
      Characterization of p53 activity and stability were assessed by quantitative PCR,
      Western blot, and immunoprecipitation. Biological outcome was measured using
      Trypan blue exclusion assay, Annexin V/PI, PARP and caspase-3 cleavage.
      Surprisingly, the overall biological effects of Nutlin-3 were more delayed (48 h)
      while MI-219 triggered an earlier response (12-24 h), predominantly in the form
      of apoptotic cell death. Using a cell free autoubiquitination assay, neither
      agent interfered with HDM2 E3 ligase function. MI-219 was more effective in
      upregulating wt-p53 stabilization compared to Nutlin-3. MI-219, but not Nutlin-3,
      enhanced the autoubiquitination and degradation of HDM2. CONCLUSIONS: Our data
      reveals unexpected differences between MI-219 and the well-studied Nutlin-3 in
      lymphoma cell lines and patient samples. We suggest a novel mechanism for MI-219
      that alters the functional activity of HDM2 through enhanced autoubiquitination
      and degradation. Additionally, this mechanism appears to correspond to biological
      outcome. Our results provide evidence that different classes of HDM2 SMIs elicit
      molecular events that extend beyond HDM2-p53 dissociation which may be of
      biological and potentially therapeutic importance.

PMID- 22989012
TI  - The effectiveness of pharmacological approaches in the treatment of alcohol
      withdrawal syndrome (AWS): a literature review.
AB  - Mortality statistics for excessive alcohol consumption show no signs of
      abatement, with a report published in 2011 from the World Health Organization
      (WHO) estimating that 2.5 million people worldwide died because of their alcohol
      consumption. Serious physiological, psychological, social and legal problems are
      thought to affect many more. Alcohol withdrawal syndrome (AWS) is a potentially
      life-threatening condition that often occurs in those individuals who
      significantly reduce or stop their intake after a prolonged and excessive period
      of drinking. Pharmacological treatment of the AWS has traditionally been
      undertaken by the use of the benzodiazepines, but recent years have witnessed the
      emergence of several alternatives. The aim of this paper was (1) to review the
      evidence base supporting the use of various pharmacological agents currently
      employed to treat AWS, and (2) to consider the efficacy and safety of the
      emerging alternatives to the benzodiazepines. The Cochrane Database of Systematic
      Reviews, CINAHL, Embase, PsycINFO, MEDLINE and BNI databases were extensively
      searched in order to retrieve the maximum number of relevant articles. Reference
      lists from relevant literature were also used to identify other potential studies
      for inclusion. All studies concerned with measuring the efficacy and safety of
      the various pharmacological treatment options for AWS were considered and a total
      of 63 trials were included in this review. Findings support the use of
      benzodiazepines as the recommended drug of choice for the treatment of AWS in the
      absence of adequate evidence to support the use of alternative agents. There is a
      lack of evidence of a superior pharmacological agent to the benzodiazepines for
      the treatment of AWS. There are several studies that have shown that there are
      pharmacological alternatives that could compete or act as an adjunct with the
      benzodiazepines in terms of high efficacy and safety in the treatment of AWS, but
      there is a need for further quality research to be carried out before definitive
      conclusions can be drawn.

PMID- 22989013
TI  - Empirical correction of nondynamical correlation energy for density functionals.
AB  - To provide an efficient means to address nondynamical correlation, an empirical
      correction for single and double hybrid density functionals has been formulated.
      The correction utilizes the highest doubly occupied, lowest unoccupied, and
      singly occupied generalized Kohn-Sham orbitals and, for potential energy curves,
      a few additional strongly correlated orbitals. Utilizing proposed nondynamical
      correlation corrections, hybrid BLYP predicted potential energy curves that fit
      well to those obtained by ab initio multireference methods for the torsional
      rotation of ethylene and the automerization of cyclobutadiene. The empirical
      nondynamical correlation corrections, calculated at the transition structures,
      also reduce the overall errors of B2K-PLYP for the DBH24 and BH76 barrier height
      data sets. The proposed empirical correction can efficiently enhance the utility
      of both single and double hybrid density functionals for chemical situations with
      moderate to significant nondynamical correlation.

PMID- 22989011
TI  - Transcriptome-scale homoeolog-specific transcript assemblies of bread wheat.
AB  - BACKGROUND: Bread wheat is one of the world's most important food crops and
      considerable efforts have been made to develop genomic resources for this
      species. This includes an on-going project by the International Wheat Genome
      Sequencing Consortium to assemble its large and complex genome, which is
      hexaploid and contains three closely related 'homoeologous' copies for each
      chromosome. This multi-national effort avoids the complications polyploidy
      entails for correct assembly of the genome by sequencing flow-sorted chromosome
      arms one at a time. Here we report on an alternate approach, a direct homoeolog
      specific assembly of the expressed portion of the genome, the transcriptome.
      RESULTS: After assessment of the ability of various assemblers to generate
      homoeolog-specific assemblies, we employed a two-stage assembly process to
      produce a high-quality assembly of the transcriptome of hexaploid wheat from
      Roche-454 and Illumina GAIIx paired-end sequence reads. The assembly process made
      use of a rapid partitioning of expressed sequences into homoeologous clusters,
      followed by a parallel high-fidelity assembly of each cluster on a 1150-processor
      compute cloud. We assessed assembly quality through comparison to known wheat
      gene sequences and found that in ca. 98.5% of cases the assembly was sufficiently
      accurate for homoeologous triplets to be cleanly separated into either two or
      three separate contigs. Comparison to publicly available transcript collections
      suggests that the assembly covers ~75-80% of the complete transcriptome.
      CONCLUSIONS: This work therefore describes the first homoeolog-specific sequence
      assembly of the wheat transcriptome and provides a reference transcriptome for
      future wheat research. Furthermore, our assembly methodology is transferable to
      other polyploid organisms.

PMID- 22989014
TI  - Small molecules based on benzo[1,2-b:4,5-b']dithiophene unit for high-performance
      solution-processed organic solar cells.
AB  - Small molecules, namely, DCAO(3)TBDT and DR(3)TBDT, with 2-ethylhexoxy
      substituted BDT as the central building block and octyl cyanoacetate and 3
      ethylrhodanine as different terminal units with the same linkage of
      dioctyltertthiophene, have been designed and synthesized. The photovoltaic
      properties of these two molecules as donors and fullerene derivatives as the
      acceptors in bulk heterojunction solar cells are studied. Among them, DR(3)TBDT
      shows excellent photovoltaic performance, and power conversion efficiency as high
      as 7.38% (certified 7.10%) under AM 1.5G irradiation (100 mW cm(-2)) has been
      achieved using the simple solution spin-coating fabrication process, which is the
      highest efficiency reported to date for any small-molecule-based solar cells. The
      results demonstrate that structure fine turning could cause significant
      performance difference and with that the performance of solution-processed small
      molecule solar cells can indeed be comparable with or even surpass their polymer
      counterparts.

PMID- 22989015
TI  - The usefulness of Real Time Morphology software in semen assessment of
      teratozoospermic boars.
AB  - The aim of the present study was to compare two different techniques of sperm
      cell morphology evaluation in teratozoospermic boars: computer assisted semen
      morphology analysis and conventional assessment of stained semen smears. The
      semen samples were collected manually from 30 boars with reduced semen quality.
      In all samples the percentage of morphologically normal spermatozoa was below
      70%. Computer assisted semen morphology assessment was performed using the Real
      Time Morphology (RTM) software (IVOS ver. 12.2, Hamilton Thorne Bioscience). The
      assessment was made by phase contrast optics, with the magnification of 20 x 3.8
      and without staining. Conventional morphology assessment was performed by bright
      field microscopy with 1,000 x magnification after staining with Giemsa. At least
      200 spermatozoa were evaluated per slide in both methods. The Bland-Altman plot
      indicated a general agreement between both methods of sperm morphology
      evaluation. The plots revealed the widest limits of agreement (mean +/- 1.96 SD)
      for the percentage of midpiece anomalies (from -16 to 13.2), and the narrowest
      for the percentage of looped tail (from -1.49 to 1.09). The Bland Altman plot
      indicates general agreement between RTM and Giemsa staining in the percentage of
      major and minor defects. However, it was not possible to evaluate acrosomes using
      RTM. Otherwise, RTM proved to be a valuable tool in sperm morphology assessment,
      with accuracy equal to typical conventional methods.

PMID- 22989016
TI  - (13)C NMR-based metabolomics for the classification of green coffee beans
      according to variety and origin.
AB  - (13)C NMR-based metabolomics was demonstrated as a useful tool for distinguishing
      the species and origins of green coffee bean samples of arabica and robusta from
      six different geographic regions. By the application of information on (13)C
      signal assignment, significantly different levels of 14 metabolites of green
      coffee beans were identified in the classifications, including sucrose, caffeine,
      chlorogenic acids, choline, amino acids, organic acids, and trigonelline, as
      captured by multivariate analytical models. These studies demonstrate that the
      species and geographical origin can be quickly discriminated by evaluating the
      major metabolites of green coffee beans quantitatively using (13)C NMR-based
      metabolite profiling. 

PMID- 22989017
TI  - Anti-Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      differentially regulate apoptosis in normal and neoplastic human basophils.
AB  - Basophilia is associated with allergic and parasitic diseases and advanced
      chronic myeloid leukemia. In the present study, we characterized the expression
      and function of the death receptors Fas/CD95 and tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) receptors in basophils from healthy donors
      compared to neoplastic basophils. Peripheral blood basophils obtained from
      healthy donors (HD-PBB) and from patients with chronic myeloid leukemia (CML-PBB)
      were found to express high levels of Fas/CD95 and low levels of TRAIL-R2, whereas
      the basophil-like chronic myeloid leukemia cell line KU-812 expressed significant
      levels of TRAIL-R1 and TRAIL-R2. HD-PBB underwent apoptosis in response to anti
      Fas/CD95, but showed resistance to TRAIL, unless they were co-treated with
      actinomycin D. Interestingly, CML-PBB and KU-812 cells exhibited the opposite
      response pattern with resistance to anti-Fas/CD95, but significant susceptibility
      to TRAIL-induced apoptosis. Our data show that anti-Fas/CD95 and TRAIL
      differentially regulate apoptosis of normal and neoplastic human basophils, which
      may direct the development of novel therapeutic strategies.

PMID- 22989018
TI  - Single domain m-plane ZnO grown on m-plane sapphire by radio frequency magnetron
      sputtering.
AB  - High-quality m-plane orientated ZnO films have been successfully grown on m-plane
      sapphire by using radio frequency magnetron sputtering deposition. The
      introduction of a nanometer-thick, low-temperature-grown ZnO buffer layer
      effectively eliminates inclusions of other undesirable orientations. The
      structure characteristics of the ZnO epi-layers were thoroughly studied by
      synchrotron X-ray scattering and transmission electron microscopy (TEM). The in
      plane epitaxial relationship between ZnO and sapphire follows (0002)(ZnO)
      [parallel] (112[overline]0)(sapphire) and (112[overline]0)(ZnO) [parallel]
      (0006)(sapphire) and the ZnO/sapphire interface structure can be described by the
      domain matching epitaxy along the [112[overline]0](ZnO) direction. The
      vibrational properties of the films were investigated by polarization dependent
      micro-Raman spectroscopy. Both XRD and micro-Raman results reveal that the
      obtained m-ZnO layers are under an anisotropic biaxial strain but still retains a
      hexagonal lattice.

PMID- 22989019
TI  - Review: immune-mediated necrotizing myopathies--a heterogeneous group of diseases
      with specific myopathological features.
AB  - Immune-mediated necrotizing myopathies (IMNMs) are now well recognized among the
      so-called idiopathic inflammatory myopathies (IIMs), which also comprise
      dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (sIBM)
      and non-specific myositis. All of these conditions are defined on the basis of
      distinct clinical symptoms, in combination with results derived from muscle
      biopsy and additional data, such as measurement of the serum creatine kinase (CK)
      level as well as myositis-associated and myositis-specific autoantibodies,
      electromyography (EMG) and modern imaging techniques. Importantly, diagnosis of
      one of the above mentioned myositis forms implies a specific clinical syndrome or
      a distinct disease. However, there is considerable clinical heterogeneity, and
      overlap requiring further diagnostic precision. Classification and
      subclassification of IIMs are highly debated and the subjects of intense
      research, especially as clinical trials with anti-inflammatory agents should
      follow universally defined and accepted criteria. This review focuses on the
      description of the spectrum of immune-mediated necrotizing myopathies with an
      emphasis on their myopathological features.

PMID- 22989021
TI  - The systematic activation method as a nursing intervention in depressed elderly:
      a protocol for a multi-centre cluster randomized trial.
AB  - BACKGROUND: Depression in later life is a common mental disorder with a
      prevalence rate of between 3% and 35% for minor depression and approximately 2%
      for Major Depressive Disorder (MDD). The most common treatment modalities for MDD
      are antidepressant medication and psychological interventions. Recently,
      Behavioral Activation (BA) has gained renewed attention as an effective treatment
      modality in MDD. Although BA is considered an easy accessible intervention for
      both patients and health care workers (such as nurses), there is no research on
      the effectiveness of the intervention in inpatient depressed elderly.The aim of
      study, described in the present proposal, is to examine the effects of BA when
      executed by nurses in an inpatient population of elderly persons with MDD.
      METHODS/DESIGN: The study is designed as a multi-center cluster randomized
      controlled trial. BA, described as The Systematic Activation Method (SAM) will be
      compared with Treatment as Usual (TAU). We aim to include ten mental health care
      units in the Netherlands that will each participate as a control unit or an
      experimental unit. The patients will meet the following criteria: (1) a primary
      diagnosis of Major Depressive Disorder (MDD) according to the DSM-IV criteria;
      (2) 60 years or older; (3) able to read and write in Dutch; (4) have consented to
      participate via the informed consent procedure. Based on an effect size d = 0.7,
      we intend to include 51 participants per condition (n = 102). The SAM will be
      implemented within the experimental units as an adjunctive therapy to Treatment
      As Usual (TAU). All patients will be assessed at baseline, after eight weeks, and
      after six months. The primary outcome will be the level of depression measured by
      means of the Beck Depression Inventory (Dutch version). Other assessments will be
      activity level, mastery, costs, anxiety and quality of life. DISCUSSION: To our
      knowledge this is the first study to test the effect of Behavioral Activation as
      a nursing intervention in an inpatient elderly population. This research has been
      approved by the medical research ethics committee for health-care settings in the
      Netherlands (No. NL26878.029.09) and is listed in the Dutch Trial Register (NTR
      No.1809).

PMID- 22989022
TI  - Comparative effects of amlodipine and benazepril on left atrial pressure in dogs
      with experimentally-induced mitral valve regurgitation.
AB  - BACKGROUND: One of the purposes of treatment for dogs with mitral regurgitation
      (MR) is lowering left atrial pressure (LAP). There has been few study of the
      amlodipine in dogs with MR and amlodipine's effect on LAP has not been fully
      evaluated in a quantitative manner because of difficulties in directly measuring
      LAP. The objective of our study was to compare the short-term effects of
      amlodipine (0.2 mg/kg PO q12h) vs benazepril (0.5 mg/kg PO q12h), on LAP and
      echocardiographic parameters in five beagle dogs with experimentally-induced MR.
      LAP of eight dogs that has own control were measured using radiotelemetry system
      at baseline and again on days 1, 2, 3, 4, 5, 6, 7 of the drug administration.
      RESULTS: Mean LAP decreased significantly after amlodipine (11.20 +/- 4.19 mmHg
      vs 14.61 +/- 3.81 mmHg at baseline, p < .01) but not after benazepril treatment
      (13.19 +/- 3.47 mmHg, p > .05). LAP was lower after 7 days of amlodipine
      treatment than after 7 days of benazepril treatment. Significant reduction was
      seen for the first time 4 days after the administration amlodipine. The rate of
      the maximal area of the regurgitant jet signals to the left atrium area (ARJ/LAA)
      of the amlodipine treatment was significantly lower (p < .05) after 7 days
      compared to baseline. Other echocardiographic parameters did not change
      significantly. CONCLUSIONS: LAP was significantly decreased after amlodipine
      treatment in dogs with surgically-induced MR but not after benazepril treatment.
      Although this study did not focus on adverse effects, amlodipine may be an
      effective drug for helping the patients with acute onset of severe MR, such as
      rupture of chordae tendinae or end stage patients were the LAP is likely to be
      elevated. Additional studies in clinical patients with degenerative mitral valve
      disease and acute chordal rupture are warranted because the blood-pressure
      lowering effects of amlodipine can decrease renal perfusion and this can further
      activate the RAAS.

PMID- 22989020
TI  - Nonfouling poly(ethylene oxide) layers end-tethered to polydopamine.
AB  - Nonfouling surfaces capable of reducing protein adsorption are highly desirable
      in a wide range of applications. Coating of surfaces with poly(ethylene oxide)
      (PEO), a water-soluble, nontoxic, and nonimmunogenic polymer, is most frequently
      used to reduce nonspecific protein adsorption. Here we show how to prepare dense
      PEO brushes on virtually any substrate by tethering PEO to polydopamine (PDA)
      modified surfaces. The chain lengths of hetero-bifunctional PEOs were varied in
      the range of 45-500 oxyethylene units (M(n) = 2000-20,000). End-tethering of PEO
      chains was performed through amine and thiol headgroups from reactive polymer
      melts to minimize excluded volume effects. Surface plasmon resonance (SPR) was
      applied to investigate the adsorption of model protein solutions and complex
      biologic medium (human blood plasma) to the densely packed PEO brushes. The level
      of protein adsorption of human serum albumin and fibrinogen solutions was below
      the detection limit of the SPR measurements for all PEO chains end-tethered to
      PDA, thus exceeding the protein resistance of PEO layers tethered directly on
      gold. It was found that the surface resistance to adsorption of lysozyme and
      human blood plasma increased with increasing length and brush character of the
      PEO chains end-tethered to PDA with a similar or better resistance in comparison
      to PEO layers on gold. Furthermore, the chain density, thickness, swelling, and
      conformation of PEO layers were determined using spectroscopic ellipsometry (SE),
      dynamic water contact angle (DCA) measurements, infrared reflection-absorption
      spectroscopy (IRRAS), and vibrational sum-frequency-generation (VSFG)
      spectroscopy, the latter in air and water.

PMID- 22989023
TI  - The effect of crank position and backrest inclination on shoulder load and
      mechanical efficiency during handcycling.
AB  - Handbikes come in different models and setups, but only limited knowledge is
      available on the handbike-user interface. The aim of this study was to identify
      optimal handbike setups, assuming that in such a setup mechanical efficiency is
      high, while shoulder load is low. Thirteen subjects with a spinal cord injury
      (paraplegia) performed handcycling with different handbike setups at constant
      power output: four crank positions (two distances, two heights) and four backrest
      inclinations. The O2-consumption, kinetics, and kinematics were measured to
      calculate mechanical efficiency and shoulder load (glenohumeral contact force,
      net shoulder moments, and rotator cuff force). The analysis showed that more
      upright backrest positions resulted in lower shoulder load compared with the most
      reclined position [glenohumeral contact force (260 vs 335 N), supraspinatus
      (14.4% vs 18.2%), and infraspinatus force (5.4% vs 9.8%)], while there was no
      difference in efficiency. Except for a reduction in subscapularis force at the
      distant position, no differences in shoulder load or efficiency were found
      between crank positions. Recreational handbike users, who want to improve their
      physical capacity in a shoulder-friendly way, should set up their handbike with a
      more upright backrest position and a distant crank placement.

PMID- 22989024
TI  - Focal high-concentration trichloroacetic acid peeling for treatment of atrophic
      facial chickenpox scar: an open-label study.
AB  - BACKGROUND: Despite their prevalence, there is a paucity of information in the
      medical literature on the treatment of atrophic chickenpox scars. OBJECTIVE: To
      evaluate the efficacy and safety of using the chemical reconstruction of skin
      scar technique for the treatment of atrophic facial chickenpox scars. METHODS AND
      MATERIALS: One hundred patients (mean age 23 years; Fitzpatrick skin types II-IV)
      were treated with focal chemical peeling with 70% trichloroacetic acid (TCA) for
      a maximum of six sessions. Improvement rate, frequency of adverse events and
      patient satisfaction were assessed. RESULTS: Five hundred thirty-three peeling
      sessions in 100 consecutive patients were performed. Final assessment at 12-week
      follow-up visit after the last treatment revealed improvement in 95% of patients:
      mild improvement in 12 cases, moderate improvement in 42 cases, and marked
      improvement in 41 cases. The appearance of scars did not change in five patients.
      Seventy-nine patients expressed moderate to high satisfaction with the results.
      Post-treatment side effects were mild and transient, resolving gradually within
      the study period. CONCLUSION: Focal peeling with high-concentration TCA appears
      to be a safe and effective alternative in the treatment of atrophic facial
      chickenpox scars.

PMID- 22989025
TI  - Dietary correlates of an at-risk BMI among Inuit adults in the Canadian high
      arctic: cross-sectional international polar year Inuit health survey, 2007-2008.
AB  - BACKGROUND: The study's objective was to investigate the dietary correlates of an
      at-risk body mass index (BMI) among Inuit adults from thirty-six communities
      across the Canadian Arctic using data from the cross-sectional International
      Polar Year Inuit Health Survey, conducted in 2007-2008. METHODS: The survey
      included assessments of 24-hr dietary recall, sociodemographics, physical
      activity, and anthropometry. Dietary characteristics of overweight and obesity
      were similar and therefore combined into one at- risk BMI category (>=25 kg/m2)
      for analyses. The relationship between an at-risk BMI and energy intake from
      macronutrients, high sugar drinks, high-fat foods, saturated fatty acids, and
      traditional foods were examined entering each dietary variable separately into a
      logistic regression model as an independent variable. Analyses were adjusted for
      age, sex, region, kcalories, walking, smoking and alcohol consumption. Further
      multivariable models considered selected dietary variables together in one model.
      RESULTS: An at-risk BMI was present for 64% with a prevalence of overweight and
      obesity of 28% and 36%, respectively. Consumption of high-sugar drinks (>15.5% E)
      was significantly related with having an at-risk BMI (OR = 1.6; 95% CI 1.2; 2.2),
      whereas the % E from total carbohydrate evaluated as a continuous variable and as
      quartiles was inversely related to an at-risk BMI (P -trend < 0.05) in
      multivariable analyses. While % E from high-fat foods was positively related to
      an at-risk BMI, the findings were not significant in a model controlling for high
      sugar drinks and % E from carbohydrates. CONCLUSIONS: The prevalence of
      overweight and obesity is of public health concern among Inuit. The current
      findings highlight the obesogenic potential of high-sugar drink consumption in an
      ethnically distinct population undergoing rapid cultural changes and raises
      concerns regarding carbohydrate restricted diets. Health promotion programs aimed
      at preventing the development of an unhealthy body weight should focus on
      physical activity and the promotion of healthy diets with reduced intake of sugar
      drinks.

PMID- 22989028
TI  - Abstracts of the AAGBI (Association of Anaesthetists of Great Britain and
      Ireland) Annual Congress. September 19-21, 2012. Bournemouth, United Kingdom.

PMID- 22989026
TI  - Assembly of the BclB glycoprotein into the exosporium and evidence for its role
      in the formation of the exosporium 'cap' structure in Bacillus anthracis.
AB  - The outermost layer of the Bacillus anthracis spore consists of an exosporium
      comprised of an outer hair-like nap layer and an internal basal layer. A major
      component of the hair-like nap is the glycosylated collagen-like protein BclA. A
      second collagen-like protein, BclB, is also present in the exosporium. BclB
      possesses an N-terminal sequence that targets it to the exosporium and is similar
      in sequence to a cognate targeting region in BclA. BclB lacks, however, sequence
      similarity to the region of BclA thought to mediate attachment to the basal layer
      via covalent interactions with the basal layer protein BxpB. Here we demonstrate
      that BxpB is critical for correct localization of BclB during spore formation and
      that the N-terminal domains of the BclA and BclB proteins compete for BxpB
      controlled assembly sites. We found that BclB is located principally in a region
      of the exosporium that excludes a short arc on one side of the exosporium (the so
      called bottle-cap region). We also found that in bclB mutant spores, the
      distribution of exosporium proteins CotY and BxpB is altered, suggesting that
      BclB has roles in exosporium assembly. In bclB mutant spores, the distance
      between the exosporium and the coat, the interspace, is reduced.

PMID- 22989029
TI  - Reversible metal-dependent destabilization and stabilization of a stem-chelate
      loop probe binding to an unmodified DNA target.
AB  - Herein, we report the discovery of a novel DNA probe with a stem-chelate-loop
      structure, wherein the stability of the probe-target duplex can be modulated
      lower or higher using a narrow concentration range of dilute transition metal
      ions (0.1-10 MUM). Oligonucleotide probes containing two terpyridine (TPY)
      ligands separated by 15 bases of single-stranded DNA, with or without a flanking
      5 base self-complementary DNA stem, were tested in thermal transition studies
      with linear target DNA and varying amounts of ZnCl(2). Without the stem, addition
      of Zn(2+) resulted only in reversible destabilization of the probe-target duplex,
      consistent with assembly (up to 1 equiv Zn(2+)) and disassembly (excess Zn(2+))
      of the intramolecular Zn(2+)-(TPY)(2) chelate. Surprisingly, probes including
      both the intramolecular chelate and the stem gave a probe-target duplex that was
      reversibly destabilized and stabilized upon addition of Zn(2+) by +/-5-7  degrees
      C, a phenomenon consistent with assembly and then disassembly of the entire stem
      Zn(2+)-(TPY)(2) motif, including the DNA stem. Stem-chelate-loop probes
      containing dipicolylamine (DPA) ligands exhibited no metal-dependent
      stabilization or destabilization. The stem-Zn(2+)-(TPY)(2) motif is readily
      introduced with automated synthesis, and may have broad utility in applications
      where it is desirable to have both upward and downward, reversible metal
      dependent control over probe-target stability involving an unmodified DNA target.

PMID- 22989030
TI  - An Egyptian family with H syndrome due to a novel mutation in SLC29A3
      illustrating overlapping features with pigmented hypertrichotic dermatosis with
      insulin-dependent diabetes and Faisalabad histiocytosis.
AB  - The SLC29A3 gene, encoding hENT3, a member of the equilibrative nucleoside
      transporter family, has recently been found mutated in Faisalabad histiocytosis,
      pigmented hypertrichotic dermatosis with insulin-dependent diabetes, familial
      sinus histiocytosis with massive lymphadenopathy (SHML), and H syndromes. We here
      report clinical and genetic findings of an Egyptian family with H syndrome. We
      describe two siblings, a 19-yr old girl and a 15-yr old boy, of consanguineous
      parents. From 5 yr of age, the girl developed bilateral flexion deformity of
      interphalengeal joints and insulin-dependent diabetes mellitus. At age 7 yr,
      prominent hyperpigmented patches appeared on the skin at lower limbs, genitalia,
      and trunk. On clinical examination, she had hepatosplenomegaly, generalized
      lymphadenopathy, left ventricular hypertrophy, sensorineural hearing loss,
      hypogonadism, short stature, and characteristic dysmorphic features. Her brother
      had fixed flexion contractures of the feet, profound sensorineural hearing loss,
      characteristic dysmorphic features, but no diabetes. DNA sequence analysis
      revealed a homozygous mutation (c.300+1G>C) in SLC29A3 in both siblings. The
      phenotype and genotype of the siblings were compatible with that of the H
      syndrome, although the features were overlapping with those found in pigmented
      hypertrichotic dermatosis with insulin-dependent diabetes, familial SHML, and
      Faisalabad histiocytosis, indicating that these four syndromes may be regarded as
      one disease with varying phenotypic features. A new, common name for these
      conditions is warranted. 

PMID- 22989031
TI  - Preoperative NT-proBNP independently predicts outcome in patients with acute
      coronary syndrome undergoing CABG.
AB  - OBJECTIVES: The predictive value of preoperative N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) was evaluated in patients with acute coronary
      syndrome undergoing coronary artery bypass grafting (CABG). DESIGN: As a substudy
      to a clinical trial 383 patients with acute coronary syndrome undergoing CABG
      were studied. 17 patients had a concomitant procedure. NT-proBNP was measured
      immediately preoperatively and evaluated with regard to in-hospital mortality,
      and severe circulatory failure postoperatively according to prespecified
      criteria. Follow-up was 3.2 +/- 0.9 years. RESULTS: In patients with isolated
      CABG, receiver operating characteristics (ROC) analysis showed an area under the
      curve (AUC) of 0.82 for in-hospital mortality and 0.87 for severe circulatory
      failure respectively with a best cut-off for preoperative NT-proBNP of 1028 ng/L.
      This cut-off level independently predicted severe circulatory failure. Patients
      with NT-proBNP < 1028 ng/L had significantly better long-term survival (p =
      0.004). Preoperative NT-proBNP was higher in patients with concomitant procedure
      than isolated CABG (2146 +/- 1858 v 887 +/- 1635 ng/L; p = 0.0005). In patients
      with concomitant procedure ROC analysis showed an AUC of 0.93 for severe
      circulatory failure with a best cut-off for preoperative NT-proBNP of 3145 ng/L.
      CONCLUSIONS: Preoperative NT-proBNP predicted in-hospital mortality, severe
      circulatory failure postoperatively and long-term survival in patients undergoing
      surgery for acute coronary syndrome but a higher threshold was found in patients
      having concomitant procedures.

PMID- 22989032
TI  - Insights into the novel hydrolytic mechanism of a diethyl 2-phenyl-2-(2
      arylacetoxy)methyl malonate ester-based microsomal triglyceride transfer protein
      (MTP) inhibitor.
AB  - Inhibition of intestinal and hepatic microsomal triglyceride transfer protein
      (MTP) is a potential strategy for the treatment of dyslipidemia and related
      metabolic disorders. Inhibition of hepatic MTP, however, results in elevated
      liver transaminases and increased hepatic fat deposition consistent with hepatic
      steatosis. Diethyl 2-((2-(3-(dimethylcarbamoyl)-4-(4'-(trifluoromethyl)-[1,1'
      biphenyl]-2-ylcarboxamido)phenyl)acetoxy)methyl)-2-phenylmalonate (JTT-130) is an
      intestine-specific inhibitor of MTP and does not cause increases in transaminases
      in short-term clinical trials in patients with dyslipidemia. Selective inhibition
      of intestinal MTP is achieved via rapid hydrolysis of its ester linkage by liver
      specific carboxylesterase(s), resulting in the formation of an inactive
      carboxylic acid metabolite 1. In the course of discovery efforts around tissue
      specific inhibitors of MTP, the mechanism of JTT-130 hydrolysis was examined in
      detail. Lack of 18O incorporation in 1 following the incubation of JTT-130 in
      human liver microsomes in the presence of H218O suggested that hydrolysis did not
      occur via a simple cleavage of the ester linkage. The characterization of atropic
      acid (2-phenylacrylic acid) as a metabolite was consistent with a hydrolytic
      pathway involving initial hydrolysis of one of the pendant malonate ethyl ester
      groups followed by decarboxylative fragmentation to 1 and the concomitant
      liberation of the potentially electrophilic acrylate species. Glutathione
      conjugates of atropic acid and its ethyl ester were also observed in microsomal
      incubations of JTT-130 that were supplemented with the thiol nucleophile.
      Additional support for the hydrolysis mechanism was obtained from analogous
      studies on diethyl 2-(2-(2-(3-(dimethylcarbamoyl)-4-(4'-trifluoromethyl)-[1,1'
      biphenyl]-2-ylcarboxamido)phenyl)acetoxy)ethyl)-2-phenylmalonate (3), which
      cannot participate in hydrolysis via the fragmentation pathway because of the
      additional methylene group. Unlike the case with JTT-130, 18O was readily
      incorporated into 1 during the enzymatic hydrolysis of 3, suggestive of a
      mechanism involving direct hydrolytic cleavage of the ester group in 3. Finally,
      3-(ethylamino)-2-(ethylcarbamoyl)-3-oxo-2-phenylpropyl 2-(3-(dimethylcarbamoyl)-4
      (4'-(trifluoromethyl)-[1,1'-biphenyl]-2-ylcarboxamido)phenyl)acetate (4), which
      possessed an N,N-diethyl-2-phenylmalonamide substituent (in lieu of the diethyl-2
      phenylmalonate motif in JTT-130) proved to be resistant to the hydrolytic
      cleavage/decarboxylative fragmentation pathway that yielded 1, a phenomenon that
      further confirmed our hypothesis. From a toxicological standpoint, it is
      noteworthy to point out that the liberation of the electrophilic acrylic acid
      species as a byproduct of JTT-130 hydrolysis is similar to the bioactivation
      mechanism established for felbamate, an anticonvulsant agent associated with
      idiosyncratic aplastic anemia and hepatotoxicity.

PMID- 22989033
TI  - Tunable wetting of polymer surfaces.
AB  - A simple method was developed for the preparation of polymeric materials with
      controlled surface wettability or tunable surface wetting. The method is
      applicable to a large number of polymers, thermoplastic or thermoset. With this
      method, it is possible to prepare polymer surfaces with static water contact
      angles ranging from 0 degrees  (superhydrophilic) to greater than 170 degrees 
      (superhydrophobic). The method developed is based on spin-coating of a
      hydrophilic/hydrophobic silica mixture dispersed in an organic solvent or solvent
      mixture onto the polymer surface. Depending on the hydrophilic/hydrophobic silica
      ratio in the coating mixture, it is possible to obtain polymer surfaces
      displaying gradually changing wettability from superhydrophilic to
      superhydrophobic. In this article, preparation and surface characteristics of
      polystyrene (PS) and cross-linked epoxy resin (ER) films are provided as general
      examples. Polymer surfaces obtained were characterized by scanning electron
      microscopy, white light interferometry, atomic force microscopy, X-ray
      photoelectron spectroscopy, and static water contact angle measurements. Effects
      of the type of polymeric substrate and composition of the silica mixture on the
      surface behavior of the composite systems were investigated.

PMID- 22989034
TI  - Hodges' Health Career Model and its role and potential application in forensic
      mental health nursing.
AB  - Forensic mental health nursing is increasingly recognized as a speciality of
      mental health nursing. Despite this, there are limited examples of theoretical
      models to underpin this specialism. This paper describes a conceptual framework
      known as the Hodges' Health Career - Care Domains - Model, hereafter referred to
      as the Health Career Model (HCM). Readers will learn of the model's origins,
      development, structure and content together with its application in forensic
      mental health nursing. Created in the 1980s, the model was developed in the North
      West of England by Brian E. Hodges. Overall, the purpose of the paper is to
      demonstrate the model's potential in forensic mental health nursing, its
      flexibility, adaptability and its increasing relevance to the problems of 21st
      century health, social care and well-being. Forensic nursing is discussed and the
      rationale for a nursing model is made. Hodges' model is introduced by explaining
      its original purposes, structure, its four knowledge (care) domains, its current
      status, publications and resources. The model's relevance and application in
      forensic nursing is explored, in particular the demands and unique constraints of
      this care environment as exercised upon service users, the multidisciplinary
      team, families, carers and other stakeholders. Future implications for research
      and recovery-orientated practice are discussed.

PMID- 22989035
TI  - Intraureteral injection of NASHA/Dx gel under direct ureteroscopic visualization
      for the treatment of primary high-grade vesicoureteral reflux.
AB  - OBJECTIVE: To present a preliminary experience with the modified technique of
      extravesical intraureteral injection of non-animal-stabilized hyaluronic
      acid/dextranomer (NASHA/Dx) gel under direct ureteroscopic visualization for the
      treatment of primary high-grade vesicoureteral reflux (VUR). PATIENTS AND
      METHODS: The medical records of all pediatric patients (age range, 0-14 years)
      who underwent intraureteral injection of NASHA/Dx gel under direct ureteroscopic
      visualization for the treatment of primary high-grade VUR during the period June
      2006-June 2010 were reviewed. RESULTS: Eighty-nine children (61 boys, 28 girls;
      M:F ratio, 2.1) underwent intraureteral injection of NASHA/Dx gel under direct
      ureteroscopic visualization for the treatment of primary high-grade VUR during
      the study period. VUR completely disappeared after the injection of NASHA/Dx gel
      into 105 (73%) of 144 ureters, with no further treatment required. Thirty-five
      (24.3%) required a second injection, and 2 (1.4%) required a third injection for
      resolution of their VUR. No intraoperative complications were observed. No
      ureteral obstruction during follow-up was observed using ultrasound or
      micturition studies. CONCLUSIONS: Intraureteral injection of NASHA/Dx gel under
      direct ureteroscopic visualization is safe and effective in the treatment of
      primary high-grade VUR, including cases with ureteral duplication, if the
      ureteral meatus is easy to pass through without mechanical dilation. This
      approach represents an effective and safe alternative to antibiotic prophylaxis
      alone and open surgery.

PMID- 22989036
TI  - Embolism risk analysis--helium versus carbon dioxide.
AB  - BACKGROUND: Helium is used as an insufflation gas to avoid the negative
      properties of carbon dioxide (CO(2)), such as CO(2) accumulation, acidosis, and
      tachycardia, particularly in the case of insufficient respiratory function, seen
      also in infancy. Any laparoscopic procedure carries the risk of a gas embolism.
      MATERIALS AND METHODS: Seven anesthetized piglets (weighing 9.9-12.8 kg),
      randomized into three groups, served as models for pre-teenage children. Three
      piglets received a CO(2) embolism, followed by a helium embolism of 2 mL/kg,
      respectively. Helium was administered to three piglets, whereas both gases were
      repeatedly administered alternately to one piglet. The embolisms were
      administered for 30 seconds via a central venous line. Cardiac output was
      measured using the thermodilution method. The observation period for each
      embolism was 60 minutes in Groups 1 and 2 and 15 minutes in Group 3. RESULTS: All
      animals survived CO(2) embolisms. Four of the six piglets died after helium
      embolisms. Following helium embolisms there was a prompt initial decrease in the
      end-tidal CO(2) pressure and an initial increase in the pulmonary arterial
      pressure. A further decrease in arterial blood pressure was prevented by a
      compensatory increase in the heart rate and appeared just before death. After
      only 5 minutes cardiac output showed a 25% decline from the initial value. Helium
      embolisms led to a severe increase in the pulmonary dead space. CONCLUSIONS:
      Embolisms with the smallest amounts of helium administered via direct venous
      puncture have an immediate lethal impact. Extended perioperative monitoring and
      trocar placement under vision should be performed.

PMID- 22989038
TI  - Single-incision transumbilical (SITU) surgery after SITU laparoscopic Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: Recently, single-incision transumbilical (SITU) laparoscopic
      bariatric surgery has been adopted as an alternative option for treating morbid
      obesity. Patients prefer SITU because it leaves minimal scarring. However, second
      surgery after SITU is a new challenge for surgeons. Here, we report on the safety
      and results for patients at a university hospital who underwent second surgery
      with the SITU procedure after SITU-laparoscopic Roux-en-Y gastric bypass (LRYGB).
      PATIENTS AND METHODS: From November 2008 to May 2011, in total, 78 morbidly obese
      patients underwent SITU-LRYGB. After follow-up, 7 cases required reoperation with
      the SITU procedure because of dilated gastrojejunostomy in 1 patient, intractable
      hiccups in 1 patient, gallstones in 2 patients, and internal hernia from
      Petersen's defect in the remaining 3 patients. SITU was repeated via the previous
      umbilical incision to avoid creating a new scar. Three trocars were inserted
      separately, and pneumoperitoneum was created. The surgical procedures were
      performed with straight instruments. All surgical results and complications were
      recorded. RESULTS: The procedure was successfully completed in all 7 patients
      without addition of trocars or conversion to conventional LRYGB or open
      procedure. Mean surgical time was 63+/-23 minutes. There were no intraoperative
      complications or postoperative wound complications noted in 3 months of follow
      up. CONCLUSIONS: Second surgery can be successfully done via a single umbilical
      incision after SITU-LRYGB, with reasonable operative time and good recovery,
      without additional abdominal scarring.

PMID- 22989037
TI  - Stitch versus scar--evaluation of laparoscopic pediatric inguinal hernia repair:
      a pilot study in a rabbit model.
AB  - BACKGROUND: Many have questioned whether the laparoscopic, percutaneous hernia
      repair technique is as durable as an open repair in which the sac is divided and
      ligated. We set out to assess if the suture alone causes enough injury and scar
      over time to obliterate the internal ring. MATERIALS AND METHODS: In total, 28
      male rabbits with congenital patent processus vaginalis underwent laparoscopic
      repair with the subcutaneous endoscopically assisted ligation technique. For
      Group 1 the repairs were evaluated laparoscopically at predetermined time points
      before and after removal of the ligating suture. Group 2 assessed the effect of
      sharp peritoneal trauma at the time of repair and was evaluated at 2 and 4 weeks.
      RESULTS: When durability of repair with suture alone was evaluated, all repairs
      failed after insufflation to 35 mm Hg after suture removal out to a time point of
      12 weeks. In the peritoneal trauma group, at the 2- and 4-week survival time
      point, 87.5% and 100%, respectively, of repairs remained intact after removal of
      suture. In contrast, only 25% and 12.5%, respectively, of defects remained closed
      in the animals repaired with suture ligation alone. CONCLUSIONS: The
      laparoscopic, percutaneous hernia repair may rely heavily on the suture itself to
      prevent recurrence. In the event of suture failure, this could lead to an
      increasingly high recurrence rate. The addition of minor peritoneum trauma may
      induce sufficient scarring to provide a more durable repair.

PMID- 22989039
TI  - Efficacy and intensity of day hospital treatment for eating disorders.
AB  - The purpose of the study was to compare the effectiveness of 4-day versus 5-day
      day hospital (DH) treatment and to document effectiveness based on a large sample
      size. Participants were 801 patients, diagnosed with an eating disorder, who
      participated in DH treatment from 1985 to 2009. The study followed a sequential
      cohort ABA design. Higher intensity DH was associated with higher rates of
      abstinence from bingeing and vomiting and larger improvements in depression and
      body dissatisfaction. Higher intensity DH provided no consistent advantage in
      rates of weight restoration or improvement on other indices of psychological
      functioning. These findings suggest that the optimal intensity of treatment may
      vary depending on treatment goals, but 5-day DH is recommended for eating
      disorders.

PMID- 22989040
TI  - Is homophobia associated with an implicit same-sex attraction?
AB  - Some theorists propose that homophobia stems from underlying same-sex attraction.
      A few studies have tested this hypothesis, yet without a clear measure of
      implicit sexual attraction, producing mixed results. For the first time, we test
      this attraction-based account of homophobia among both men and women using an
      implicit measure of sexual attraction. No evidence of an attraction-based account
      of homophobia emerged. Instead, implicit same-sex attraction was related to
      positive evaluations of gay men and lesbians among female participants. Even in
      targeted analyses examining the relation between implicit same-sex attraction and
      homosexual evaluations among only those theoretically most likely to demonstrate
      an attraction-based homophobic effect, implicit same-sex attraction was not
      associated with evaluations of homosexuals or was associated with more positive
      evaluations of homosexuals. In addition, explicit same-sex attraction was related
      to positive evaluations of gay men and lesbians for male participants. These
      results are more in keeping with the attitude-similarity effect (i.e., people
      like, rather than dislike, similar others). 

PMID- 22989041
TI  - Photoconversion of a protonated diarylethene derivative.
AB  - A photochromic diarylethene with N,N-dimethyl substituted group 1a was prepared.
      1a showed ring-opening and ring-closing photoisomerization with UV/vis light
      irradiation. Treatment of 1a with CF(3)COOH produced a protonated diarylethene
      1aH. With UV light irradiation, 1aH photoconverted to protonated ring-closed
      isomer 1c, which is photoinactive. It is found that 1c is hydrophilic and 1aH is
      hydrophobic.

PMID- 22989042
TI  - The effectiveness of probiotics for managing diarrhoea in people with HIV
      infection: a critically appraised topic.
AB  - OBJECTIVES: The implications of HIV infection are vast. Management of clinical
      symptomatology, though, cannot be overshadowed by focus on disease management.
      These must be managed in concert. Diarrhoea, a common complaint of HIV-infected
      people, can be difficult to manage, and complicated further by polypharmacy. This
      review will critically appraise literature related to the management of diarrhoea
      with probiotics in HIV-infected people. METHODS: PubMed, CINAHL, and The Cochrane
      Library were searched for randomized controlled trials investigating the use of
      probiotics in HIV-infected people, which included diarrhoeal symptoms as a
      primary or secondary endpoint. RESULTS: Three randomized controlled trials and
      one randomized control cross-over study were identified as best evidence. One
      study identified a statistically significant improvement in diarrhoea for those
      treated with probiotics. An additional study identified improvement in diarrhoea;
      however, a similar improvement was seen in those treated with placebo. Two
      studies did not identify a statistical difference for those treated with
      probiotics. CONCLUSIONS: There is insufficient evidence to allow a strong
      recommendation to be made for or against the use of probiotics for diarrhoea, but
      safety and lack of drug-drug interactions make it a reasonable option for some
      patients.

PMID- 22989044
TI  - Direct writing patterns for electroless plated copper thin film on plastic
      substrates.
AB  - A simple and efficient method is developed to create conductive copper thin films
      on polymer surfaces. Instead of regular palladium colloid inks, micropatterns of
      silver nitrate inks, which serve as an activating agent for copper plating, were
      printed and dried on flexible plastic substrates. The printed plastic sheets were
      then immersed in an electroless copper plating bath at 55  degrees C for 2 min to
      create copper thin films on the printed patterns. The prepared copper films have
      an electrical conductivity as high as 83% of bulk copper and show good adhesion
      on PET or PI substrates.

PMID- 22989043
TI  - Risk of subsequent biliary malignancy in patients undergoing cyst excision for
      congenital choledochal cysts.
AB  - BACKGROUND AND AIM: The aim of this study was to elucidate the risk of subsequent
      biliary malignancy in patients undergoing cyst excision for congenital
      choledochal cysts. METHODS: A retrospective analysis of 94 patients who had
      undergone cyst excision for congenital choledochal cysts was conducted. The
      median age at the time of cyst excision and median follow-up time after cyst
      excision were 7 years and 181 months, respectively. RESULTS: Biliary tract cancer
      developed in four patients at 13, 15, 23, and 32 years after cyst excision. The
      cumulative incidences of biliary tract cancer at 15, 20, and 25 years after cyst
      excision were 1.6%, 3.9%, and 11.3%, respectively. The sites of biliary tract
      cancer were the intrahepatic (n = 2), hilar (n = 1), and intrapancreatic (n = 1)
      bile ducts. Of the four patients with biliary tract cancer after cyst excision,
      three patients underwent surgical resection and one patient received chemo
      radiotherapy. The overall cumulative survival rates after treatment in the four
      patients with biliary tract cancer were 50% at 2 years and 25% at 3 years, with a
      median survival time of 15 months. CONCLUSIONS: The risk of subsequent biliary
      malignancy in patients undergoing cyst excision for congenital choledochal cysts
      seems to be relatively high in the long-term. The risk of biliary malignancy in
      the remnant bile duct increases more than 15 years after cyst excision. Despite
      an aggressive treatment approach for this condition, subsequent biliary
      malignancy following cyst excision for congenital choledochal cysts shows an
      unfavorable outcome.

PMID- 22989045
TI  - Long-term interdisciplinary therapy reduces endotoxin level and insulin
      resistance in obese adolescents.
AB  - AIM: The purpose of the present study was to assess the dietary fat intake,
      glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR,
      and endotoxin levels and correlate them with adipokine serum concentrations in
      obese adolescents who had been admitted to long-term interdisciplinary weight
      loss therapy. DESIGN: The present study was a longitudinal clinical intervention
      of interdisciplinary therapy. Adolescents (n = 18, aged 15-19 y) with a body mass
      index > 95th percentile were admitted and evaluated at baseline and again after 1
      year of interdisciplinary therapy. We collected blood samples, and IL-6,
      adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was
      measured using 3-day diet records. In addition, we assessed glucose and insulin
      levels as well as the homeostasis model assessment for insulin resistance (HOMA
      IR). RESULTS: The most important finding from the present investigation was that
      the long-term interdisciplinary lifestyle therapy decreased dietary fat intake
      and endotoxin levels and improved HOMA-IR. We observed positive correlations
      between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR.
      In addition, endotoxin levels showed positive correlations with IL-6 levels,
      insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation
      between serum adiponectin and both dietary fat intake and endotoxin levels.
      CONCLUSIONS: The present results indicate an association between dietary fat
      intake and endotoxin level, which was highly correlated with a decreased pro
      inflammatory state and an improvement in HOMA-IR. In addition, this benefits
      effect may be associated with an increased adiponectin level, which suggests that
      the interdisciplinary therapy was effective in improving inflammatory pathways.

PMID- 22989046
TI  - Systematic evaluation of three different commercial software solutions for
      automatic segmentation for adaptive therapy in head-and-neck, prostate and
      pleural cancer.
AB  - PURPOSE: To validate, in the context of adaptive radiotherapy, three commercial
      software solutions for atlas-based segmentation. METHODS AND MATERIALS: Fifteen
      patients, five for each group, with cancer of the Head&Neck, pleura, and prostate
      were enrolled in the study. In addition to the treatment planning CT (pCT)
      images, one replanning CT (rCT) image set was acquired for each patient during
      the RT course. Three experienced physicians outlined on the pCT and rCT all the
      volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2
      (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the
      automatic contouring on the repeated CT. All the VOIs obtained with automatic
      contouring (AC) were successively corrected manually. We recorded the time needed
      for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software
      solutions; 3) manual correction of AC.To compare the quality of the volumes
      obtained automatically by the software and manually corrected with those drawn
      from scratch on rCT, we used the following indexes: overlap coefficient (DICE),
      sensitivity, inclusiveness index, difference in volume, and displacement
      differences on three axes (x, y, z) from the isocenter. RESULTS: The time saved
      by the three software solutions for all the sites, compared to the manual
      contouring from scratch, is statistically significant and similar for all the
      three software solutions. The time saved for each site are as follows: about an
      hour for Head&Neck, about 40 minutes for prostate, and about 20 minutes for
      mesothelioma. The best DICE similarity coefficient index was obtained with the
      manual correction for: A (contours for prostate), A and M (contours for H&N), and
      M (contours for mesothelioma). CONCLUSIONS: From a clinical point of view, the
      automated contouring workflow was shown to be significantly shorter than the
      manual contouring process, even though manual correction of the VOIs is always
      needed.

PMID- 22989047
TI  - Orally administered Lactobacillus rhamnosus modulates the respiratory immune
      response triggered by the viral pathogen-associated molecular pattern poly(I:C).
AB  - BACKGROUND: Some studies have shown that probiotics, including Lactobacillus
      rhamnosus CRL1505, had the potential to beneficially modulate the outcome of
      certain bacterial and viral respiratory infections. However, these studies did
      not determine the mechanism(s) by which probiotics contribute to host defense
      against respiratory viruses. RESULTS: In this work we demonstrated that orally
      administered Lactobacillus rhamnosus CRL1505 (Lr1505) was able to increase the
      levels of IFN-gamma, IL-10 and IL-6 in the respiratory tract and the number of
      lung CD3(+)CD4(+)IFN-gamma(+) T cells. To mimic the pro-inflammatory and
      physiopathological consecuences of RNA viral infections in the lung, we used an
      experimental model of lung inflammation based on the administration of the
      artificial viral pathogen-associated molecular pattern poly(I:C). Nasal
      administration of poly(I:C) to mice induced a marked impairment of lung function
      that was accompanied by the production of pro-inflammatory mediators and
      inflammatory cell recruitment into the airways. The preventive administration of
      Lr1505 reduced lung injuries and the production of TNF-alpha, IL-6, IL-8 and MCP
      1 in the respiratory tract after the challenge with poly(I:C). Moreover, Lr1505
      induced a significant increase in lung and serum IL-10. We also observed that
      Lr1505 was able to increase respiratory IFN-gamma levels and the number of lung
      CD3(+)CD4(+)IFN-gamma(+) T cells after poly(I:C) challenge. Moreover, higher
      numbers of both CD103(+) and CD11b(high) dendritic cells and increased expression
      of MHC-II, IL-12 and IFN-gamma in these cell populations were found in lungs of
      Lr1505-treated mice. Therefore, Lr1505 treatment would beneficially regulate the
      balance between pro-inflammatory mediators and IL-10, allowing an effective
      inflammatory response against infection and avoiding tissue damage. CONCLUSIONS:
      Results showed that Lr1505 would induce a mobilization of cells from intestine
      and changes in cytokine profile that would be able to beneficially modulate the
      respiratory mucosal immunity. Although deeper studies are needed using challenges
      with respiratory viruses, the results in this study suggest that Lr1505, a potent
      inducer of antiviral cytokines, may be useful as a prophylactic agent to control
      respiratory virus infection.

PMID- 22989048
TI  - Shared genomic segment analysis: the power to find rare disease variants.
AB  - Shared genomic segment (SGS) analysis uses dense single nucleotide polymorphism
      genotyping in high-risk (HR) pedigrees to identify regions of sharing between
      cases. Here, we illustrate the power of SGS to identify dominant rare risk
      variants. Using simulated pedigrees, we consider 12 disease models based on
      disease prevalence, minor allele frequency and penetrance to represent disease
      loci that explain 0.2-99.8% of total disease risk. Pedigrees were required to
      contain >= 15 meioses between all cases and to be HR based on significant excess
      of disease (P < 0.001 or P < 0.00001). Across these scenarios, the power for a
      single pedigree ranged widely. Nonetheless, fewer than 10 pedigrees were
      sufficient for excellent power in the majority of models. Power increased with
      the risk attributable to the disease locus, penetrance and the excess of disease
      in the pedigree. Sharing allowing for one sporadic case was uniformly more
      powerful than sharing using all cases. Furthermore, an SGS analysis using a large
      attenuated familial adenomatous polyposis pedigree identified a 1.96 Mb region
      containing the known causal APC gene with genome-wide significance. SGS is a
      powerful method for detecting rare variants and a valuable complement to genome
      wide association studies and linkage analysis.

PMID- 22989050
TI  - Multiple squamous cell carcinomas and eruptive keratoacanthomas in an arc welder.

PMID- 22989051
TI  - Effects of repeated intravitreal bevacizumab injections on the inner retinal
      function in neovascular age-related macular degeneration.

PMID- 22989049
TI  - Biomarkers and molecular probes for cell death imaging and targeted therapeutics.
AB  - Cell death is a critically important biological process. Disruption of
      homeostasis, either by excessive or deficient cell death, is a hallmark of many
      pathological conditions. Recent research advances have greatly increased our
      molecular understanding of cell death and its role in a range of diseases and
      therapeutic treatments. Central to these ongoing research and clinical efforts is
      the need for imaging technologies that can locate and identify cell death in a
      wide array of in vitro and in vivo biomedical samples with varied spatiotemporal
      requirements. This review article summarizes community efforts over the past five
      years to identify useful biomarkers for dead and dying cells, and to develop
      molecular probes that target these biomarkers for optical, radionuclear, or
      magnetic resonance imaging. Apoptosis biomarkers are classified as either
      intracellular (caspase enzymes, mitochondrial membrane potential, cytosolic
      proteins) or extracellular (plasma membrane phospholipids, membrane potential,
      surface exposed histones). Necrosis, autophagy, and senescence biomarkers are
      described, as well as unexplored cell death biomarkers. The article discusses
      possible chemotherapeutic and theranostic strategies, and concludes with a
      summary of current challenges and expected eventual rewards of clinical cell
      death imaging.

PMID- 22989052
TI  - Synergistic effect of oleic acid and glycerol on zein film plasticization.
AB  - Oleic acid and glycerol are two different molecules with different plasticization
      mechanisms, and their effects on the mechanical properties of zein film were
      investigated. The mechanical parameters of tensile strength (TS) and elongation
      to break (E) were improved by either oleic acid or glycerol in a dose-dependent
      manner up to 20%. When a combination of the two plasticizers in different ratios
      was used to make zein films, the highest TS was observed at a ratio of 3:1 of
      oleic acid to glycerol, and a synergy between them was revealed through a
      statistical analysis. A significant decrease of glass transition temperature (Tg)
      and different microscopic patterns examined by scanning electronic microscopy
      (SEM) indicate the supramolecular structure was changed by the plasticizers. A
      combination of plasticizers with different plasticization mechanisms might be a
      better way to synergistically improve the mechanical properties of biopolymer
      based films for practical applications. 

PMID- 22989053
TI  - Tumor-to-tumor metastasis from pituitary carcinoma to radiation-induced
      meningioma.
AB  - Radiation-induced meningioma and pituitary carcinoma are both uncommon. Tumor-to
      tumor metastasis (TTM) from pituitary carcinoma to meningioma, to our knowledge,
      has not been previously reported. A 67-year old man presented with a previous
      history of transcranial subtotal resection of pituitary adenoma, at the age of
      36, followed by radiotherapy. The follow-up was uneventful for the following 31
      years. The patient presented with worsening sight and numbness of the right arm.
      Three separate lesions were found on MRI. Histological examinations revealed
      pituitary carcinomas and TTM from pituitary carcinoma to meningioma. A constant
      surveillance is necessary for patients with pituitary tumor, especially those
      followed by radiotherapy.

PMID- 22989054
TI  - ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder.
AB  - BACKGROUND: In recent years, the identification of peripheral biomarkers that are
      associated with psychiatric diseases, such as Major Depressive Disorder (MDD),
      has become relevant because these biomarkers may improve the efficiency of the
      differential diagnosis process and indicate targets for new antidepressant drugs.
      Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels
      have been found to be altered in the leukocytes of patients that are affected by
      bipolar disorder in a depressive state. On this basis, the aim of the study was
      to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD.
      METHODS: We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in
      leukocytes of MDD patients compared with controls. Successively, to assess
      whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we
      stratified our patients sample in two cohorts, comparing drug-naive versus drug
      free patients. Moreover, we evaluated the levels of the transcript in MDD
      patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of
      rats stressed and treated with an antidepressant drug of the same class. RESULTS:
      These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in
      leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3
      levels were not affected by antidepressant treatment in either human or animal
      models CONCLUSIONS: Our data suggest that ErbB3 might be considered as a
      biomarker for MDD and that its deficit may underlie the pathophysiology of the
      disease and is not a consequence of treatment. Moreover the study supports the
      usefulness of leukocytes as a peripheral system for identifying biomarkers in
      psychiatric diseases.

PMID- 22989056
TI  - Are the national orthopaedic thromboprophylaxis guidelines appropriate?
AB  - BACKGROUND: To identify enablers and barriers to thromboprophylaxis prescribing
      following hip and knee arthroplasty, from the perspective of orthopaedic
      surgeons. METHODS: An invitation to participate in an online survey was
      distributed electronically to Arthroplasty Society of Australia members (n =
      103). The survey collected demographic details, thromboprophylaxis attitudes and
      clinical practice of the orthopaedic surgeons, and explored their familiarity
      with contemporary national and international guidelines. RESULTS: Twenty-five
      surgeons (24%) completed the survey, all male with a median of 20 years of
      practice as orthopaedic surgeons (range: 8-27 years). Most surgeons (92%)
      practised predominantly in the private sector, and conducted both hip and knee
      arthroplasties each month. While all surgeons prescribed chemoprophylaxis
      following arthroplasty, most surgeons (64%) were uncertain to what extent it
      would prevent fatal pulmonary embolism (PE). The pharmacological agents of choice
      were low molecular weight heparin (48%) and aspirin (44%). One-third of surgeons
      were not familiar with the National Health and Medical Research Council
      recommendations for thromboprophylaxis in hip and knee arthroplasty patients.
      After reviewing a summary of the recommendations, most surgeons (80%) indicated
      they were inappropriate, commonly citing that they were grounded on an
      insufficient evidence base and should include aspirin as a sole chemoprophylaxis
      option. CONCLUSION: There are clearly strong barriers to the translation of
      current thromboprophylaxis guidelines into practice. Many surgeons doubt the
      effectiveness of chemoprophylaxis to prevent fatal PE, perceive the risk of
      venous thromboembolism following surgery to be low, are unfamiliar with current
      national guidelines or believe the guidelines are grounded on inappropriate
      evidence.

PMID- 22989055
TI  - Immunohystochemical analysis of CFTR in normal and disrupted spermatogenesis.
AB  - Cystic fibrosis is the most frequent autosomal recessive disease in the Caucasian
      population, with an incidence of 1:2500 newborn and a frequency of 1:25. The
      associated gene is Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and
      it encodes the CFTR protein that functions as a chloride (Cl(-)) channel. It is
      found in the apical membrane of exocrine epithelial cells, responsible for the
      regulation of the movement of water and solutes through biological membranes. To
      our knowledge, there are no studies on protein localization in the different cell
      types of the seminiferous epithelium with different pathologies. The aim of the
      present study was to analyze the expression of the CFTR protein in the human
      seminiferous epithelium of infertile males with different pathologies. CFTR
      protein expression was studied by immunohistochemistry in paraffin sections of
      testicular biopsies of six infertile men: Sertoli cell only syndrome, maturation
      arrest, secondary obstructive azoospermia, primary obstructive azoospermia due to
      congenital bilateral absence of the vas deferens (CBAVD), severe oligozoospermia,
      and retrograde ejaculation. All cell types of the seminiferous epithelium were
      studied: Sertoli cells, spermatogonia, primary spermatocytes at the
      leptotene/zygotene and at the pachytene stages, secondary spermatocytes, round,
      elongating and elongated spermatids, and spermatozoa. With the exception of
      sperm, all cells were labeled in the cytoplasm and in the cytoplasmic membrane.
      In the patient with CBAVD labeling was light at the cell membrane and absent in
      the cytoplasm of Sertoli cells and diploid germ cells. Generally, labeling was
      stronger after the diploid stage, which is probably related to cell volume
      reduction during spermiogenesis. The results obtained also suggest that the CFTR
      protein may impact CBAVD spermatogenesis and other pathologies.

PMID- 22989057
TI  - Aortic regurgitation after transcatheter aortic valve implantation of the Edwards
      SAPIEN TM valve.
AB  - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is established as an
      attractive treatment option for high-risk patients with aortic valve stenosis.
      One concern is the high risk of prosthetic valve regurgitation. This study aimed
      to examine for potential preoperative risk factors for postprocedural
      transcatheter heart valve regurgitation and to quantify the risk, degree, and
      consequences of postprocedural regurgitation. MATERIALS AND METHODS: 100
      consecutive patients who underwent femoral (n = 22) or transapical (n = 78) TAVI
      were retrospectively reviewed. Echocardiographic valve regurgitation and clinical
      parameters were analyzed over the first year after TAVI. RESULTS: Seventy-five
      percent of all patients had prosthetic valve regurgitation. It was, however, only
      mild or absent in 64% of patients and did not require re-intervention in any of
      the patients in the series. The severity of the regurgitation appeared unchanged
      over the one-year follow-up period. Moderate to severe regurgitation was
      associated with significant yet stable dilatation of the left ventricle over one
      year and lesser NYHA class improvement three months after TAVI. Asymmetrical
      native valve calcification increased the risk of paravalvular regurgitation non
      significantly. CONCLUSION: Transcatheter heart valve regurgitation seems to be
      mild in the majority of cases and unchanged over a 12 months follow-up period.
      While affecting left ventricular dimensions in moderate or severe cases, we
      observed no obvious undesirable consequences of the prosthetic valve
      regurgitation within the first year.

PMID- 22989058
TI  - Are MXenes promising anode materials for Li ion batteries? Computational studies
      on electronic properties and Li storage capability of Ti3C2 and Ti3C2X2 (X = F,
      OH) monolayer.
AB  - Density functional theory (DFT) computations were performed to investigate the
      electronic properties and Li storage capability of Ti(3)C(2), one representative
      MXene (M represents transition metals, and X is either C or/and N) material, and
      its fluorinated and hydroxylated derivatives. The Ti(3)C(2) monolayer acts as a
      magnetic metal, while its derived Ti(3)C(2)F(2) and Ti(3)C(2)(OH)(2) in their
      stable conformations are semiconductors with small band gaps. Li adsorption forms
      a strong Coulomb interaction with Ti(3)C(2)-based hosts but well preserves its
      structural integrity. The bare Ti(3)C(2) monolayer exhibits a low barrier for Li
      diffusion and high Li storage capacity (up to Ti(3)C(2)Li(2) stoichiometry). The
      surface functionalization of F and OH blocks Li transport and decreases Li
      storage capacity, which should be avoided in experiments. The exceptional
      properties, including good electronic conductivity, fast Li diffusion, low
      operating voltage, and high theoretical Li storage capacity, make Ti(3)C(2) MXene
      a promising anode material for Li ion batteries.

PMID- 22989059
TI  - Liver histopathology in the cane toad, Rhinella marina (Amphibia: Bufonidae),
      induced by Ortleppascaris sp. larvae (Nematoda: Ascarididae).
AB  - Exposure to parasites is considered to be an important factor in the development
      of many diseases and histopathologies which are the result of the parasite-host
      interaction. The present study evaluated the impact of natural infection by
      larvae of Ortleppascaris sp. (Nematoda: Ascaridida) in the liver of the cane toad
      Rhinella marina (Linnaeus, 1758). Larvae were encysted in nodules delimited by
      collagenous fibers and fibroblasts or freely within the hepatic parenchyma,
      provoking a clear response from the host. The histological examination of the
      liver revealed viable larvae in a number of different developmental stages, as
      well as cysts filled with amorphous material and cell residues and surrounded by
      dense fibrotic tissue. The infection of the liver by these larvae induces a
      significant increase in the area occupied by melanomacrophages and a reduction or
      deficit in the vascularization of the liver, hypertrophy of the hepatocytes,
      vacuolar bodies, and cytoplasmatic granules. Focal concentrations of inflammatory
      infiltrates were observed enclosing the unencapsulated early-stage larvae. These
      results indicate that infection by Ortleppascaris sp. induces severe
      physiological problems and histopathological lesions in the liver of R. marina .

PMID- 22989060
TI  - Protect Lake Victoria through green economy, public participation and good
      governance.

PMID- 22989061
TI  - Consequences of interfacial viscoelasticity on thin film stability.
AB  - The phenomenon of dewetting is frequently observed in our everyday life. It is of
      central importance in many technological applications as well as in a variety of
      physical and biological systems. The presence of nonsoluble surfactants at an
      air/liquid interface may affect the dewetting properties of the aqueous layer. An
      important example is the tear film, which comprises an aqueous layer covered with
      a ~100-nm-thick blanket of lipids, known as the meibomian lipids. Interfacial
      rheological measurements of meibomian lipids reveal that these films are
      remarkably viscoelastic. Tear film dewetting is of central importance to
      understanding tear film stability. To better understand the role of surface
      viscoelasticity in tear film stability, we have developed a methodology to
      systematically control interfacial rheology of thin aqueous layers at the onset
      of dewetting events. The apparatus allows control over the surface pressure of
      the monolayer, which is a key feature since this variable controls the surface
      viscoelasticity. Three insoluble monolayer materials were used: newtonian
      arachidyl alcohol (AA), DPPC, a phospholipid that is slightly viscoelastic, and
      meibum, which produces a strongly viscoelastic monolayer. It is reported that
      monolayers of viscoelastic surfactants are able to stabilize thin films against
      spontaneous dewetting. As the surface pressure of these layers is increased,
      their effectiveness is enhanced. Moreover, these surfactants are able to reduce
      the critical film thickness for dewetting. Meibum is particularly effective in
      stabilizing thin films. Our results suggest that the meibomian lipids play a
      vital role in maintaining tear film stability in addition to suppressing
      evaporation.

PMID- 22989063
TI  - DNA barcoding South China Sea fishes.
AB  - We have determined 222 DNA barcode sequences of 95 fish species in 86 genera of
      69 families from 15 orders. Fish were captured by trawl from two important
      fisheries regions in South China Sea: Spratly Islands (Nansha Islands) and Beibu
      Gulf. The average genetic distances between intraspecies were about 60-fold less
      than those of interspecies within different taxonomic levels, as Kimura two
      parameter genetic distances averaged 17.260% among congeners, 20.097% among
      genus, and only 0.317% for intraspecific individuals. There were a few examples
      of deep divergence within species, suggesting the need for further taxonomic
      work, and a few examples of closely allied species, perhaps reflecting
      introgressive hybridization. The results provide further evidence for the
      reliability and accessibility of DNA barcodes for marine fish identification, and
      also highlight their effectiveness for flagging cases needing taxonomical
      reexamination.

PMID- 22989064
TI  - An evaluation of a collaborative bibliotherapy scheme delivered via a library
      service.
AB  - This paper reports on the evaluation of a bibliotherapy scheme delivered via a
      local library service, in conjunction with General Practice (GP) practices, local
      social welfare agencies and through self-referral. The Read Yourself Well (RYW)
      scheme was based on principles established from other similar schemes and as a
      way of delivering support for adults experiencing mild to moderate mental health
      problems for whom clinical treatments are not appropriate. The intervention
      consisted of initial referral and evaluation by the scheme bibliotherapist, a one
      hour session at the beginning and end of the intervention where a purpose
      designed questionnaire and two mental health assessments were carried out (the
      General Health Questionnaire and the Clinical Outcomes in Routine Evaluation
      questionnaire). Contact and support from the bibliotherapist was provided during
      the intervention period. One hundred and fifty-seven participants were recruited
      to the evaluation of whom 114 provided full data. Statistical analyses of the
      mental health scores showed significant improvements post treatment, for, both
      male and female participants, for all three referral routes, and for participants
      who were previously library users, and those who joined the library service to
      participate in the RYW scheme. The results of this large sample evaluation
      support the proposal that library-based bibliotherapy can be effective in the
      treatment of mental health problems.

PMID- 22989065
TI  - Metabolic labeling of human bone marrow mesenchymal stem cells for the
      quantitative analysis of their chondrogenic differentiation.
AB  - Human mesenchymal stem cells (hMSCs), residing in bone marrow as well as in the
      synovial lining of joints, can be triggered to differentiate toward chondrocytes.
      Thus, hMSCs harbor great therapeutic potential for the repair of cartilage
      defects in osteoarthritis (OA) and other articular diseases. However, the
      molecular mechanisms underlying the chondrogenesis process are still in part
      unknown. In this work, we applied for the first time the stable isotope labeling
      by amino acids in cell culture (SILAC) technique for the quantitative analysis of
      protein modulation during the chondrogenic differentiation process of hMSCs.
      First, we have standardized the metabolic labeling procedure on MSCs isolated
      from bone marrow (hBMSCs), and we have assessed the quality of chondrogenesis
      taking place in these conditions. Then, chondrogenic differentiation was induced
      on these labeled cells, and a quantitative proteomics approach has been followed
      to evaluate protein changes between two differentiation days. With this strategy,
      we could identify 622 different proteins by LC-MALDI-TOF/TOF analysis and find 65
      proteins whose abundance was significantly modulated between day 2 and day 14 of
      chondrogenesis. Immunohistochemistry analyses were performed to verify the
      changes on a panel of six proteins that play different biological roles in the
      cell: fibronectin, gelsolin, vimentin, alpha-ATPase, mitochondrial superoxide
      dismutase, and cyclophilin A. All of these proteins were increased at day 14
      compared to day 2 of chondrogenic induction, thus being markers of the enhanced
      extracellular matrix synthesis, cell adhesion, metabolism, and response to stress
      processes that take place in the early steps of chondrogenesis. Our strategy has
      allowed an additional insight into both specific protein function and the
      mechanisms of chondrogenesis and has provided a panel of protein markers of this
      differentiation process in hBMSCs.

PMID- 22989066
TI  - Prostate cancer incidence and newly diagnosed patient profile in Spain in 2010.
AB  - What's known on the subject? and What does the study add? Prostate cancer (PCa)
      accounts for 12% of newly diagnosed cases of cancer in Europe. It is one of the
      most frequently diagnosed tumours in the developed world. Since the introduction
      of prostate specific antigen as a test for early detection of PCa, the rate of
      diagnosis has increased significantly and specific mortality has reduced in most
      western countries. Most of the data on the incidence of PCa are obtained from
      population-based cancer registries which frequently do not cover the whole
      population. This first national hospital-based PCa registry aims not only to
      estimate the incidence of the disease but to ascertain the clinical profile of
      newly diagnosed PCa patients, a useful tool for evaluating the impact of the
      disease and its socio-health management. OBJECTIVES: * To estimate the 2010
      incidence of prostate cancer (PCa) in Spain. * To describe the clinical profile
      of newly diagnosed cases using a nationwide hospital-based registry. PATIENTS AND
      METHODS: * This was a national epidemiological observational study in 25 public
      hospitals with a specific reference population according to the National Health
      System. * Sociodemographic and clinical variables of all newly diagnosed,
      histopathologically confirmed PCa cases were collected in 2010, in the area of
      influence of each centre. Cases diagnosed in private practice were not collected
      (estimated nearly 10% in Spain). * Data monitoring was external to guarantee
      quality and homogeneity. * The age-standardized PCa incidence was determined
      based on the age distribution of the European standard population. RESULTS: * In
      all, 4087 new cases of PCa were diagnosed for a reference population of 4933940
      men (21.8% of the Spanish male population). * The estimated age-standardized PCa
      incidence was 70.75 cases per 100000 men. * Mean age at diagnosis was 69 years;
      11.6% of patients presented with tumour-related symptoms and 39.5% with LUTS.
      Median PSA was 8 ng/mL. Gleason score was <= 6 in 56.5%, 7 in 26.7% and >7 in
      16.8% of patients. At diagnosis, 89.8% had localized, 6.4% locally advanced and
      3.8% metastatic disease. CONCLUSIONS: * This study on PCa incidence in Spain, a
      western country with intensive opportunistic PSA screening, shows that PCa is a
      high incidence tumour, diagnosed close to 70 years, usually asymptomatic. *
      Almost 40% of cases have low risk disease with a risk of over-diagnosis and over
      treatment. * Around 55% of patients with intermediate or high risk disease are
      candidates for active therapy which may result in a reduction of cancer-specific
      mortality.

PMID- 22989069
TI  - Electroreduction and acid-base properties of dipyrrolylquinoxalines.
AB  - The electroreduction and acid-base properties of dipyrrolylquinoxalines of the
      form H(2)DPQ, H(2)DPQ(NO(2)), and H(2)DPQ(NO(2))(2) were investigated in
      benzonitrile (PhCN) containing 0.1 M tetra-n-butylammonium perchlorate (TBAP).
      This study focuses on elucidating the complete electrochemistry,
      spectroelectrochemistry, and acid-base properties of H(2)DPQ(NO(2))(n) (n = 0, 1,
      or 2) in PhCN before and after the addition of trifluoroacetic acid (TFA), tetra
      n-butylammonium hydroxide (TBAOH), tetra-n-butylammonium fluoride (TBAF), or
      tetra-n-butylammonium acetate (TBAOAc) to solution. Electrochemical and
      spectroelectrochemical data provide support for the formation of a
      monodeprotonated anion after disproportionation of a dipyrrolylquinoxaline
      radical anion produced initially. The generated monoanion is then further reduced
      in two reversible one-electron-transfer steps at more negative potentials in the
      case of H(2)DPQ(NO(2)) and H(2)DPQ(NO(2))(2). Electrochemically monitored
      titrations of H(2)DPQ(NO(2))(n) with OH(-), F(-), or OAc(-) (in the form of
      TBA(+)X(-) salts) give rise to the same monodeprotonated H(2)DPQ(NO(2))(n)
      produced during electroreduction in PhCN. This latter anion can then be reduced
      in two additional one-electron-transfer steps in the case of H(2)DPQ(NO(2)) and
      H(2)DPQ(NO(2))(2). Spectroscopically monitored titrations of H(2)DPQ(NO(2))(n)
      with X(-) show a 1:2 stoichiometry and provide evidence for the production of
      both [H(2)DPQ(NO(2))(n)](-) and XHX(-). The spectroscopically measured
      equilibrium constants range from log beta(2) = 5.3 for the reaction of H(2)DPQ
      with TBAOAc to log beta(2) = 8.8 for the reaction of H(2)DPQ(NO(2))(2) with
      TBAOH. These results are consistent with a combined deprotonation and anion
      binding process. Equilibrium constants for the addition of one H(+) to each
      quinoxaline nitrogen of H(2)DPQ, H(2)DPQ(NO(2)), and H(2)DPQ(NO(2))(2) in PhCN
      containing 0.1 M TBAP were also determined via electrochemical and spectroscopic
      means; this gave rise to log beta(2) values ranging from 0.7 to 4.6, depending
      upon the number of nitro substituents present on the H(2)DPQ core. The redox
      behavior of the H(2)DPQ(NO(2))(n) compounds of the present study were further
      analyzed through comparisons with simple quinoxalines that lack the two linked
      pyrrole groups, i.e., Q(NO(2))(n) where n = 0, 1, or 2. It is concluded that the
      pyrrolic substituents play a critical role in regulating the electrochemical and
      spectroscopic features of DPQs.

PMID- 22989067
TI  - Genomic impact of cigarette smoke, with application to three smoking-related
      diseases.
AB  - There is considerable evidence that inhaled toxicants such as cigarette smoke can
      cause both irreversible changes to the genetic material (DNA mutations) and
      putatively reversible changes to the epigenetic landscape (changes in the DNA
      methylation and chromatin modification state). The diseases that are believed to
      involve genetic and epigenetic perturbations include lung cancer, chronic
      obstructive pulmonary disease (COPD), and cardiovascular disease (CVD), all of
      which are strongly linked epidemiologically to cigarette smoking. In this review,
      we highlight the significance of genomics and epigenomics in these major smoking
      related diseases. We also summarize the in vitro and in vivo findings on the
      specific perturbations that smoke and its constituent compounds can inflict upon
      the genome, particularly on the pulmonary system. Finally, we review state-of-the
      art genomics and new techniques such as high-throughput sequencing and genome
      wide chromatin assays, rapidly evolving techniques which have allowed epigenetic
      changes to be characterized at the genome level. These techniques have the
      potential to significantly improve our understanding of the specific mechanisms
      by which exposure to environmental chemicals causes disease. Such mechanistic
      knowledge provides a variety of opportunities for enhanced product safety
      assessment and the discovery of novel therapeutic interventions.

PMID- 22989068
TI  - The effects of indoor environmental exposures on pediatric asthma: a discrete
      event simulation model.
AB  - BACKGROUND: In the United States, asthma is the most common chronic disease of
      childhood across all socioeconomic classes and is the most frequent cause of
      hospitalization among children. Asthma exacerbations have been associated with
      exposure to residential indoor environmental stressors such as allergens and air
      pollutants as well as numerous additional factors. Simulation modeling is a
      valuable tool that can be used to evaluate interventions for complex
      multifactorial diseases such as asthma but in spite of its flexibility and
      applicability, modeling applications in either environmental exposures or asthma
      have been limited to date. METHODS: We designed a discrete event simulation model
      to study the effect of environmental factors on asthma exacerbations in school
      age children living in low-income multi-family housing. Model outcomes include
      asthma symptoms, medication use, hospitalizations, and emergency room visits.
      Environmental factors were linked to percent predicted forced expiratory volume
      in 1 second (FEV1%), which in turn was linked to risk equations for each outcome.
      Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5,
      cockroach allergen, and dampness as a proxy for mold. RESULTS: Model design
      parameters and equations are described in detail. We evaluated the model by
      simulating 50,000 children over 10 years and showed that pollutant concentrations
      and health outcome rates are comparable to values reported in the literature. In
      an application example, we simulated what would happen if the kitchen and
      bathroom exhaust fans were improved for the entire cohort, and showed reductions
      in pollutant concentrations and healthcare utilization rates. CONCLUSIONS: We
      describe the design and evaluation of a discrete event simulation model of
      pediatric asthma for children living in low-income multi-family housing. Our
      model simulates the effect of environmental factors (combustion pollutants and
      allergens), medication compliance, seasonality, and medical history on asthma
      outcomes (symptom-days, medication use, hospitalizations, and emergency room
      visits). The model can be used to evaluate building interventions and green
      building construction practices on pollutant concentrations, energy savings, and
      asthma healthcare utilization costs, and demonstrates the value of a simulation
      approach for studying complex diseases such as asthma.

PMID- 22989071
TI  - Quality control of saffron (Crocus sativus L.): development of SCAR markers for
      the detection of plant adulterants used as bulking agents.
AB  - A method based on sequence-characterized amplified regions (SCARs) was developed
      from random amplified polymorphic DNA markers (RAPDs) specific for Arnica montana
      L., Bixa orellana L., Calendula officinalis L., Carthamus tinctorius L., Crocus
      vernus L. (Hill), Curcuma longa L., and Hemerocallis sp. to detect these common
      bulking agents in commercial saffron (Crocus sativus). The method enabled the
      unequivocal detection of low amounts (up to 1%) of each adulterant, allowing the
      preemptive rejection of suspect samples. Its enforcement limits the number of
      samples to be subjected to further evaluation with pharmacognostic or
      phytochemical analyses, especially when multiple batches have to be evaluated in
      a short time. The dimension of the amplicons is suitable for the analysis of
      degraded DNA obtained from dried, stored, processed, and finely ground commercial
      material. Proper SCAR markers may represent a fast, sensitive, reliable, and low
      cost screening method for the authentication of dried commercial saffron
      material.

PMID- 22989070
TI  - Proteomics of Streptococcus gordonii within a model developing oral microbial
      community.
AB  - BACKGROUND: Streptococcus gordonii is one of several species that can initiate
      the formation of oral biofilms that develop into the complex multispecies
      microbial communities referred to as dental plaque. It is in the context of
      dental plaque that periodontal pathogens such as Porphyromonas gingivalis cause
      disease. We have previously reported a whole cell quantitative proteomics
      investigation of P. gingivalis in a model dental plaque community of S. gordonii,
      P. gingivalis, and Fusobacterium nucleatum. Here we report the adaptation of S.
      gordonii to the same model. RESULTS: 1122 S. gordonii proteins were detected in
      S. gordonii control samples, 915 in communities with F. nucleatum, 849 with P.
      gingivalis, and 649 with all three organisms. Quantitative comparisons showed
      extensive proteome changes in association with F. nucleatum or P. gingivalis
      individually or both P. gingivalis and F. nucleatum together. The changes were
      species specific, though the P. gingivalis interaction may be dominant, indicated
      by large differences between the proteomes with F. nucleatum or P. gingivalis but
      limited changes between communities with P. gingivalis or both P. gingivalis and
      F. nucleatum. The results were inspected manually and an ontology analysis
      conducted using DAVID. Extensive changes were seen in nutrition pathways with
      increases in energy metabolism and changes in the resulting byproducts, while the
      acid and sugar repressed PTS (phosphoenolpyruvate dependent phosphotransferase
      system) sugar transport systems showed decreases. These results were seen across
      all the multispecies samples, though with different profiles according to the
      partner species. F. nucleatum association decreased proteins for the metabolic
      end products acetate and ethanol but increased lactate, the primary source of
      acidity from streptococcal cultures. P. gingivalis containing samples had a
      reduction in levels of proteins for ethanol and formate but increased proteins
      for both acetate and lactate production. The communities also showed increases in
      exopolysaccharide synthesis, amino acid biosynthesis, and oxidative stress
      protection and decreases in adhesion and transporter proteins. CONCLUSION: This
      study showed that S. gordonii demonstrates species specific responses during
      interactions with F. nucleatum or P. gingivalis. Extensive changes were seen in
      energy metabolism and byproduct production implicating nutrient transfer as an
      important community interaction.

PMID- 22989073
TI  - Author reply to Holford, Vu and Nutt regarding 'Piecing together the puzzle of
      progression and mortality in Parkinson's disease'.

PMID- 22989072
TI  - Sex-related differences in sleep slow wave activity in major depressive disorder:
      a high-density EEG investigation.
AB  - BACKGROUND: Sleep disturbance plays an important role in major depressive
      disorder (MDD). Prior investigations have demonstrated that slow wave activity
      (SWA) during sleep is altered in MDD; however, results have not been consistent
      across studies, which may be due in part to sex-related differences in SWA and/or
      limited spatial resolution of spectral analyses. This study sought to
      characterize SWA in MDD utilizing high-density electroencephalography (hdEEG) to
      examine the topography of SWA across the cortex in MDD, as well as sex-related
      variation in SWA topography in the disorder. METHODS: All-night recordings with
      256 channel hdEEG were collected in 30 unipolar MDD subjects (19 women) and 30
      age and sex-matched control subjects. Spectral analyses of SWA were performed to
      determine group differences. SWA was compared between MDD and controls, including
      analyses stratified by sex, using statistical non-parametric mapping to correct
      for multiple comparisons of topographic data. RESULTS: As a group, MDD subjects
      demonstrated significant increases in all-night SWA primarily in bilateral
      prefrontal channels. When stratified by sex, MDD women demonstrated global
      increases in SWA relative to age-matched controls that were most consistent in
      bilateral prefrontal regions; however, MDD men showed no significant differences
      relative to age-matched controls. Further analyses demonstrated increased SWA in
      MDD women was most prominent in the first portion of the night. CONCLUSIONS:
      Women, but not men with MDD demonstrate significant increases in SWA in multiple
      cortical areas relative to control subjects. Further research is warranted to
      investigate the role of SWA in MDD, and to clarify how increased SWA in women
      with MDD is related to the pathophysiology of the disorder.

PMID- 22989074
TI  - Morphogenesis underlying the development of the everted teleost telencephalon.
AB  - BACKGROUND: Although the mechanisms underlying brain patterning and
      regionalization are very much conserved, the morphology of different brain
      regions is extraordinarily variable across vertebrate phylogeny. This is
      especially manifest in the telencephalon, where the most dramatic variation is
      seen between ray-finned fish, which have an everted telencephalon, and all other
      vertebrates, which have an evaginated telencephalon. The mechanisms that generate
      these distinct morphologies are not well understood. RESULTS: Here we study the
      morphogenesis of the zebrafish telencephalon from 12 hours post fertilization
      (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle
      formation, evolving patterns of gene and transgene expression, neuronal
      organization, and fate mapping. Our results highlight two key events in
      telencephalon morphogenesis. First, the formation of a deep ventricular recess
      between telencephalon and diencephalon, the anterior intraencephalic sulcus
      (AIS), effectively creates a posterior ventricular wall to the telencephalic
      lobes. This process displaces the most posterior neuroepithelial territory of the
      telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed
      between days 2 and 5 of development, the pallial region of the posterior
      ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS.
      This brings the ventricular zone (VZ) into close apposition with the roof of the
      AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As
      the pallial VZ expands, the tc also expands over the upper surface of the
      telencephalon. During this period, the major axis of growth and extension of the
      pallial VZ is along the anteroposterior axis. This second step effectively
      generates an everted telencephalon by 5 dpf. CONCLUSION: Our description of
      telencephalic morphogenesis challenges the conventional model that eversion is
      simply due to a laterally directed outfolding of the telencephalic
      neuroepithelium. This may have significant bearing on understanding the eventual
      organization of the adult fish telencephalon.

PMID- 22989075
TI  - Natural direct and indirect effects on the exposed: effect decomposition under
      weaker assumptions.
AB  - We define natural direct and indirect effects on the exposed. We show that these
      allow for effect decomposition under weaker identification conditions than
      population natural direct and indirect effects. When no confounders of the
      mediator-outcome association are affected by the exposure, identification is
      possible under essentially the same conditions as for controlled direct effects.
      Otherwise, identification is still possible with additional knowledge on a
      nonidentifiable selection-bias function which measures the dependence of the
      mediator effect on the observed exposure within confounder levels, and which
      evaluates to zero in a large class of realistic data-generating mechanisms. We
      argue that natural direct and indirect effects on the exposed are of intrinsic
      interest in various applications. We moreover show that they coincide with the
      corresponding population natural direct and indirect effects when the exposure is
      randomly assigned. In such settings, our results are thus also of relevance for
      assessing population natural direct and indirect effects in the presence of
      exposure-induced mediator-outcome confounding, which existing methodology has not
      been able to address.

PMID- 22989076
TI  - Bimodal anti-glioma mechanisms of cilengitide demonstrated by novel invasive
      glioma models.
AB  - Integrins are expressed in tumor cells and tumor endothelial cells, and likely
      play important roles in glioma angiogenesis and invasion. We investigated the
      anti-glioma mechanisms of cilengitide (EMD121974), an alphavbeta3 integrin
      inhibitor, utilizing the novel invasive glioma models, J3T-1 and J3T-2.
      Immunohistochemical staining of cells in culture and brain tumors in rats
      revealed positive alphavbeta3 integrin expression in J3T-2 cells and tumor
      endothelial cells, but not in J3T-1 cells. Established J3T-1 and J3T-2 orthotopic
      gliomas in athymic rats were treated with cilengitide or solvent. J3T-1 gliomas
      showed perivascular tumor cluster formation and angiogenesis, while J3T-2 gliomas
      showed diffuse single-cell infiltration without obvious angiogenesis. Cilengitide
      treatment resulted in a significantly decreased diameter of the J3T-1 tumor
      vessel clusters and its core vessels when compared with controls, while an anti
      invasive effect was shown in the J3T-2 glioma with a significant reduction of
      diffuse cell infiltration around the tumor center. The survival of cilengitide
      treated mice harboring J3T-1 tumors was significantly longer than that of control
      animals (median survival: 57.5 days and 31.8 days, respectively, P < 0.005),
      while cilengitide had no effect on the survival of mice with J3T-2 tumors (median
      survival: 48.9 days and 48.5, P = 0.69). Our results indicate that cilengitide
      exerts a phenotypic anti-tumor effect by inhibiting angiogenesis and glioma cell
      invasion. These two mechanisms are clearly shown by the experimental treatment of
      two different animal invasive glioma models.

PMID- 22989078
TI  - Characteristics of basal cell carcinoma of the lip treated using Mohs
      micrographic surgery.
AB  - BACKGROUND: There is a lack of U.S-based studies on basal cell carcinoma (BCC) of
      the upper lip treated using Mohs micrographic surgery (MMS). OBJECTIVE: To
      explore characteristics of BCC of the upper lip treated using MMS. METHODS: We
      performed a chart review of BCC cases from 2005 to 2011. RESULTS: Two hundred
      eighty-one cases were identified. There was a slight female predominance (55%).
      Men had a larger initial (p < .01) and final (p = .03) defect size. Infiltrative
      tumors had larger initial (p < .01) and final areas (p < .01). Ten percent of
      tumors were designated recurrent after previous treatment. Recurrent lesions (p <
      .001) and older age (p = .03) were associated with larger initial size. Complex
      reconstruction was required: 44% by local flap or graft and 13% by plastic
      surgery. CONCLUSION: There was a 1.2:1 female to male ratio, in contrast to the
      previously reported female predominance of 3.5:1. This cohort showed a higher
      recurrence rate than reported in the literature. Men and elderly patients were
      also found to have significantly larger initial lesion size. Thirteen percent of
      patients required repair by plastic surgery, reflecting heightened levels of
      cosmetic concern. These findings suggest that MMS is important in delineating
      subclinical tumor spread and providing complex repairs.

PMID- 22989079
TI  - What is the optimal dosage for intravitreal bevacizumab for retinopathy of
      prematurity?

PMID- 22989077
TI  - Music's use for anesthesia and analgesia.
AB  - This review article provides an overview of published data regarding the
      involvement of music in anesthesia practice. Music is an important topic for
      research in different fields of anesthesiology. The use of music preoperatively
      is aimed at reducing anxiety, stress, and fear. However, the effect of music on
      perception of pain intraoperatively is controversial, according to studies of
      both adults and children undergoing various surgical procedures under general
      and/or regional anesthesia. In postoperative pain management, postanesthesia
      care, and neonatal intensive care, music can be a complementary method for
      reducing pain, anxiety, and stress. Music is a mild anxiolytic, but it is
      relatively ineffective when a pain stimulus is severe. However, music is
      inexpensive, easily administered, and free of adverse effects, and as such, can
      serve as complementary method for treating perioperative stress and for acute and
      chronic pain management, even though music's effectiveness depends on each
      individual patient's disposition and severity of pain stimulus.

PMID- 22989080
TI  - Decoration of TiO2 nanotubes with metal nanoparticles using polyoxometalate as a
      UV-switchable reducing agent for enhanced visible and solar light photocatalysis.
AB  - We present the employment of the Keggin ion 12-phosphotungstic acid as a UV
      switchable reducing agent for the decoration of Au, Ag, Pt, and Cu nanoparticles
      onto the surface of TiO(2) nanotubes synthesized by electrochemical anodization.
      The synthesized composites were studied using SEM, GADDS XRD, and EDX, and the
      photocatalytic activity of the composites was examined by measuring the
      photodegradation of the organic dye "Congo red" under simulated solar light.
      Decoration with metal nanoparticles was observed to enhance the activity of the
      photocatalytic process by upward of 100% with respect to unmodified TiO(2)
      nanotubes.

PMID- 22989081
TI  - Use of scintigraphy to evaluate gastric accommodation and emptying: comparison
      with barostat.
AB  - BACKGROUND AND AIM: Scintigraphy is a useful noninvasive technique for assessment
      of gastric motility, especially emptying, but there is little knowledge of use of
      the technique to assess gastric accommodation. Therefore, to clarify the
      usefulness of scintigraphy as a technique for assessing gastric accommodation, we
      compared scintigraphy with barostat, the gold standard modality. METHODS: Twenty
      healthy volunteers (14 men, six women; mean age, 28.5 +/- 5.4 years) were
      enrolled in the study. The volunteers ingested a radiolabeled ((99m) Tc) test
      meal and scintigraphic images were recorded. Radioactivity in the upper third and
      whole stomach was calculated to evaluate accommodation. In the barostat
      procedure, gastric accommodation was evaluated by measuring the maximum volume of
      the distended balloon. Thereafter, correlation between scintigraphic and barostat
      accommodation was investigated. Intra-and inter-observer variation of the
      scintigraphic test results were also assessed. Finally, the diagnostic
      performance of scintigraphy was evaluated by using sumatriptan as a positive
      control. RESULTS: Measurements of accommodation by scintigraphy and barostat
      correlated (r = 0.524, P < 0.05). Sumatriptan significantly increased
      scintigraphically measured gastric accommodation (with sumatriptan, 51.5 +/-
      16.4%; without sumatriptan, 38.4 +/- 13.8%) (P < 0.01), and had significantly (P
      < 0.05) delayed 50% half emptying time at 60, 90, 120, and 150 min after the
      start of the experiment. The data from repeated scintigraphic tests were highly
      reproducible (r = 0.804) with significant differences not observed among the
      investigators (inter-observer variation = 0.932, intra-observer variation =
      0.898). CONCLUSION: Gastric scintigraphy is a useful technique for assessing
      gastric accommodation and emptying.

PMID- 22989083
TI  - Photodriven charge separation dynamics in CdSe/ZnS core/shell quantum
      dot/cobaloxime hybrid for efficient hydrogen production.
AB  - Photodriven charge-transfer dynamics and catalytic properties have been
      investigated for a hybrid system containing CdSe/ZnS core/shell quantum dots
      (QDs) and surface-bound molecular cobaloxime catalysts. The electron transfer
      from light-excited QDs to cobaloxime, revealed by optical transient absorption
      spectroscopy, takes place with an average time constant of 105 ps, followed a
      much slower charge recombination process with a time constant of ?3 ns. More
      interestingly, we also observed photocatalytic hydrogen generation by this
      QD/cobaloxime hybrid system, with >10,000 turnovers of H(2) per QD in 10 h, using
      triethanolamine as a sacrificial electron donor. These results suggest that
      QD/cobaloxime hybrids succeed in coupling single-photon events with multielectron
      redox catalytic reactions, and such systems could have potential applications in
      long-lived artificial photosynthetic devices for fuel generation from sunlight.

PMID- 22989082
TI  - Pharmacokinetics and tissue distribution of amphotericin B following oral
      administration of three lipid-based formulations to rats.
AB  - The objective of this study was to assess the pharmacokinetics and tissue
      distribution of amphotericin B (AmB) in rats following oral administration of
      three lipid-based formulations (iCo-009, iCo-010 and iCo-011). The lipid-based
      formulations were administered to rats at a dose of 10 mg/kg and blood samples
      were withdrawn at predose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 h, after which
      the animals were sacrificed and the body organs were collected for AmB
      quantification using a validated HPLC method. Plasma pharmacokinetics parameters
      were determined using non-compartmental analysis. The disappearance of AmB from
      plasma was the slowest following the administration of iCo-010 with MRT of 63 h
      followed by iCo-009 then iCo-011 (36 and 27 h). The AUC(0-24h) of iCo-009 and iCo
      010 was 1.5-2-fold higher than that of iCo-011. The kidney exposure was
      comparable between iCo-009 and iCo-010 and was higher than that of iCo-011. The
      lung exposure was the highest following iCo-010 administration as compared to
      that of iCo-009. The distribution of AmB from plasma to tissues resulted in a
      high accumulation of AmB overtime with slow back-distribution to plasma. The
      pharmacokinetics profiles varied among the three formulations, despite the
      similarity in lipid composition between iCo-010 and iCo-011 and the presence of
      Peceol(r) as a common component in the formulations. The administration of oral
      iCo-010 could lead to higher steady state concentrations in the tissues after
      multiple dosing, which could lead to enhanced eradication of tissue borne fungal
      and parasitic infections.

PMID- 22989085
TI  - Review of para-articular soft tissue osteochondromas of the knee.
AB  - Para-articular osteochondromas (PAOCs) are a rare benign subtype of chondroma
      that occur in the soft tissues around the joints. Initially hypothesized to be
      derived from cartilaginous metaplasia, its aetiology and pathogenesis are still
      not fully understood. This tumour often causes a diagnostic and management
      dilemma due to similar clinical and histopathological features compared with
      other pathology. We report the fourth case of PAOC arising from the suprapatella
      region of the knee joint and review the literature to update our understanding of
      this tumour. From the data analysed, a distinctive pattern of tumour formation
      within or adjacent to a fat pad structure was evident, while trauma appears to
      play a role in its pathogenesis. Histologically, the tumour consists of a
      cartilage cap, with varying degrees of trabecular bone and endochondral
      ossification. Importantly, there are no features of nuclear pleomorphism or
      increased mitotic activity suggestive of a malignant process. All tumours were
      surgically removed and behaved in a benign fashion without evidence of
      recurrence. PAOC may often be suspected for more malignant processes; thus,
      recognition of this entity is important as simple excision is curative.

PMID- 22989087
TI  - High-intensity focused ultrasound in prostate cancer: today's outcomes and
      tomorrow's perspectives.
AB  - High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied
      for prostate cancer that capitalizes on the coagulation necrosis that occurs at
      temperatures greater than 60 degrees C. Owing to a lack of long-term follow-up
      data the procedure is still considered experimental treatment. As primary
      therapy, HIFU is indicated in patients aged >=70 years with clinical organ
      confined disease, although it has also been used, with encouraging results, as
      first line salvage therapy after definitive treatment, and in locally advanced
      (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated
      with this treatment method appears to be low and includes urinary retention (1
      9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13
      53%) and rectourethral fistulae (0-3%). The risk of complications increases with
      repeated treatments. A few studies have recently been published on HIFU as focal
      therapy. HIFU technology can be enhanced using means such as ultrasound
      microbubble contrast agents for assessment of therapy efficacy, magnetic
      resonance imaging to guide the enhancement of heat rate, and localized drug and
      gene delivery.

PMID- 22989086
TI  - Effects of aerobic exercise training on serum sex hormone binding globulin, body
      fat index, and metabolic syndrome factors in obese postmenopausal women.
AB  - BACKGROUND: The percentage of obese postmenopausal women with metabolic syndrome
      is rising, and physical factors associated with the metabolic syndrome prevalence
      or incidence are also rising, including high body mass index (BMI), visceral fat
      area (VFA), low plasma sex hormone-binding globulin (SHBG) levels, and low
      cardiorespiratory fitness. Therefore, we investigated the influence of aerobic
      exercise on SHBG, body fat index (BFI), and metabolic syndrome factors in obese
      postmenopausal Korean women. METHODS: Thirty healthy postmenopausal, women aged
      53.46 +/- 2.4 years and with over 32% body fat, were randomly assigned to an
      aerobic exercise group (EX; n=15) or to a "nonexercise" control (Con; n=15)
      group. The primary outcome measurements were serum SHBG, lipid profiles, insulin
      levels, and metabolic syndrome factors. Secondary outcome measurements were body
      composition, VFA, blood pressure (BP), and homeostasis model assessment of
      insulin resistance (HOMA-IR). RESULTS: Posttraining body weight and BFI (P<0.05),
      total cholesterol, glucose, and insulin levels (P<0.01), BP, and HOMA-IR
      (P<0.001) decreased, whereas SHBG (P<0.001) and metabolic syndrome factors
      (P<0.01) improved in the exercise group but not in the control group. SHBG levels
      also showed a significant positive correlation with high-density lipoprotein
      cholesterol (HDL-C) and significant negative correlations withglucose, diastolic
      blood pressure, fat mass, BMI, and percent body fat (P<0.05). CONCLUSIONS: Our
      findings indicate that aerobic exercise improves body composition, SHBG, insulin
      levels, and metabolic syndrome factors. These findings suggest that in
      obesepostmenopausal Korean women, 16 weeks of aerobic exercise is effective for
      preventing the metabolic syndrome caused by obesity.

PMID- 22989088
TI  - The impact of training and delivering alcohol brief intervention on the knowledge
      and attitudes of community pharmacists: a before and after study.
AB  - INTRODUCTION AND AIMS: Alcohol misuse is the third leading cause of ill health in
      the UK. Alcohol brief intervention can identify risky drinkers and motivate
      individuals to take action. Community pharmacists have been identified as having
      a role in providing brief interventions. This study aimed to evaluate:
      pharmacists' attitudes towards hazardous/harmful drinkers and knowledge before
      training and after delivering brief intervention; and their experience of
      training. DESIGN AND METHODS: Pharmacists' attitudes to alcohol problems were
      assessed using Short Alcohol and Alcohol Problems Perception Questions before
      training and after brief intervention delivery. Alcohol misuse knowledge was
      assessed by questionnaire prior to and immediately after training, and after the
      delivery period. Following brief intervention delivery, pharmacists' experience
      of training was obtained using a questionnaire and focus groups. Qualitative
      thematic analysis identified experiences of brief intervention training.
      Quantitative data were analysed using spss. RESULTS: One hundred and thirty-nine
      alcohol interventions were delivered by 19 pharmacists over five months
      (recruiters). Ten pharmacists completed no interventions (non-recruiters). Both
      groups improved their alcohol knowledge between baseline and immediately
      following training; and their knowledge decreased between the end of training and
      following service delivery. Pharmacists who were initially more motivated
      recruited more participants and increased their work satisfaction. DISCUSSION AND
      CONCLUSIONS: This confirmed findings of previous studies that pharmacists
      unfamiliar with brief intervention could be trained to deliver this service.
      Pharmacists with positive attitude towards drinkers delivered a greater number of
      alcohol interventions and experienced increased work satisfaction than those
      pharmacists with less positive attitudes.

PMID- 22989089
TI  - Millimeter-scale resolution of trace metal distributions in microbial mats from a
      hypersaline environment in Baja California, Mexico.
AB  - Microbial mats from two ponds with different salinities from the saltern of
      Guerrero Negro (Mexico) points toward millimeter-scale coherent variations in
      trace metal (Me) concentrations (Cd, Co, Cu, Fe, Mn, Ni, Pb, Zn). Total, HCl
      leachable and pyrite-associated Me showed a trend of increasing concentrations
      with increasing depth suggesting gradual addition of reactive Me probably as a
      result of metal sulfide precipitation at depth. The trends in Me profiles can be
      ascribed to the establishment and maintenance of microzones that promote
      geochemical processes, bacterial population distributions, and differential mass
      transport within the mats. Degrees of trace metal pyritization (1 +/- 1% for Zn
      to 24 +/- 7% for Cd) as well as metals associated with the pyrite fraction (<1.4
      36 +/- 18 nmol g(-1) for Zn and Mn, respectively) were low, as expected from a
      reactive Fe-limited system like Guerrero Negro. Calculated enrichment factors
      showed that Ni (2.6 +/- 2.1), Co (5.5 +/- 4.0), Pb (9.4 +/- 7.4), and Cd (57 +/-
      39) were, on average, enriched in the microbial mats of Guerrero Negro. Natural
      enrichments of Cd, Pb, and Co in sediments along the coast of Baja California and
      metabolical requirements of Co and Ni by the predominant cyanobacteria in the
      Guerrero Negro mats may explain these enrichments. Metal characteristics in
      microbial mats could be advantageously used as biosignatures to identify their
      presence in the geological record or in other planetary systems.

PMID- 22989090
TI  - Economic evaluations of prophylaxis with clotting factor for people with severe
      haemophilia: why do the results vary so much?
AB  - A number of studies examining the cost effectiveness of haemophilia prophylaxis
      have been published, but they report a wide range of results. The aim of this
      study was to explain why the results from existing economic evaluations of
      prophylaxis with clotting factor vary so much and to suggest areas of further
      research that will help to generate stronger economic evidence. Results from a
      previous systematic review were updated using a textword search of a number of
      electronic databases. Eleven economic evaluations were identified. They reported
      incremental cost-effectiveness ratios for prophylaxis ranging from 'cost saving
      and clinically beneficial' (i.e. 'dominant') to over ?1 million per additional
      quality-adjusted life year (QALY) if prophylaxis replaces treatment following a
      bleed. A number of reasons are likely to explain this breadth of results, most
      notably differences in choice of time horizon, estimates of treatment effect,
      clotting factor unit cost, discount rates and definitions of prophylaxis.
      Although the existing cost-effectiveness literature for haemophilia prophylaxis
      appears to report a wide range of results, closer inspection suggests that
      differences are largely explained by a number of design features. Some are likely
      to reflect local economic conditions and should be expected. However, others,
      such as differences in the choice of appropriate time horizon, are more
      concerning as they reflect differences in opinion over appropriate methodology. A
      number of studies to help address these evidence gaps are suggested: however, it
      is also recommended that analysts continue to adhere to established conventions
      when conducting and reporting economic evaluations.

PMID- 22989091
TI  - A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant
      with an alternative exon 1 potentially encoding an extended N-terminus.
AB  - BACKGROUND: The major rate-limiting enzyme for de novo cholesterol synthesis is 3
      hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). HMGCR is sterically
      inhibited by statins, the most commonly prescribed drugs for the prevention of
      cardiovascular events. Alternative splicing of HMGCR has been implicated in the
      control of cholesterol homeostasis. The aim of this study was to identify novel
      alternatively spliced variants of HMGCR with potential physiological importance.
      RESULTS: Bioinformatic analyses predicted three novel HMGCR transcripts
      containing an alternative exon 1 (HMGCR-1b, -1c, -1d) compared with the canonical
      transcript (HMGCR-1a). The open reading frame of the HMGCR-1b transcript
      potentially encodes 20 additional amino acids at the N-terminus, compared with
      HMGCR-1a. Reverse transcription quantitative polymerase chain reaction (RT-qPCR)
      was used to examine the mRNA levels of HMGCR in different tissues; HMGCR-1a was
      the most highly expressed variant in most tissues, with the exception of the
      skin, esophagus, and uterine cervix, in which HMGCR-1b was the most highly
      expressed transcript. Atorvastatin treatment of HepG2 cells resulted in increased
      HMGCR-1b mRNA levels, but unaltered proximal promoter activity compared to
      untreated cells. In contrast, HMGCR-1c showed a more restricted transcription
      pattern, but was also induced by atorvastatin treatment. CONCLUSIONS: The gene
      encoding HMGCR uses alternative, mutually exclusive exon 1 sequences. This
      contributes to an increased complexity of HMGCR transcripts. Further studies are
      needed to investigate whether HMGCR splice variants identified in this study are
      physiologically functional.

PMID- 22989092
TI  - Dietary Fructus Schisandrae extracts and fenofibrate regulate the serum/hepatic
      lipid-profile in normal and hypercholesterolemic mice, with attention to
      hepatotoxicity.
AB  - BACKGROUND: Schisandra, a globally distributed plant, has been widely applied to
      health care products. Here, we investigated the effects of dietary intake of
      Fructus Schisandrae chinensis (FSC), both aqueous and ethanolic extracts (AqFSC,
      EtFSC), on serum/hepatic lipid contents in normal diet (ND)- and high
      fat/cholesterol/bile salt diet (HFCBD)-fed mice. METHODS: Male ICR mice were fed
      with ND or HFCBD, supplemented with 1 and 4% of AqFSC and EtFSC, respectively, or
      0.1% fenofibrate, for 13 days. Lipids were determined according to the
      manufacture's instructions. RESULTS: EtFSC, but not AqFSC, significantly elevated
      hepatic triglyceride (TG) in mice fed with ND. Feeding mice with HFCBD increased
      serum total cholesterol (TC), high density lipoprotein (HDL) and low density
      lipoprotein (LDL) levels as well as alanine aminotransferase (ALT) activity.
      Supplementation with AqFSC, EtFSC or fenofibrate significantly reduced hepatic TC
      and TG levels. However, AqFSC and EtFSC supplementation increased serum HDL and
      LDL levels in mice fed with HFCBD. Fenofibrate increased serum HDL and reduced
      serum LDL contents in hypercholesterolemic mice. EtFSC reduced, but fenofibrate
      elevated, serum ALT activity in both normal and hypercholesterolemic mice. While
      fenofibrate reduced serum TC, TG, and HDL levels in mice fed with ND, it
      increased serum HDL and reduced serum LDL and TC levels in mice fed with HFCBD.
      Hepatomegaly was found in normal and hypercholesterolemic mice fed with diet
      supplemented with fenofibrate. CONCLUSIONS: Feeding mice with AqFSC and EtFSC
      ameliorated the HFCBD-induced hepatic steatosis. In addition, EtFSC may offer
      protection against hepatic injury in hypercholesterolemic mice.

PMID- 22989093
TI  - Disaster exposure as a risk factor for mental health problems, eighteen months,
      four and ten years post-disaster--a longitudinal study.
AB  - BACKGROUND: Disaster experiences have been associated with higher prevalence
      rates of (mental) health problems. The objective of this study was to examine the
      independent relation between a series of single disaster experiences versus the
      independent predictive value of a accumulation of disaster experiences, i.e. a
      sum score of experiences and symptoms of distress and post-traumatic stress
      disorder (PTSD). METHODS: Survivors of a fireworks disaster participated in a
      longitudinal study and completed a questionnaire three weeks (wave 1), eighteen
      months (wave 2) and four years post-disaster (wave 3). Ten years post-disaster
      (wave 4) the respondents consisted of native Dutch survivors only. Main outcome
      measures were general distress and symptoms of PTSD. RESULTS: Degree of disaster
      exposure (sum score) and some disaster-related experiences (such as house
      destroyed, injured, confusion) were related to distress at waves 2 and 3. This
      relation was mediated by distress at an earlier point in time. None of the
      individual disaster-related experiences was independently related to symptoms of
      distress. The association between the degree of disaster exposure and symptoms of
      PTSD at waves 2 and 3 was still statistically significant after controlling for
      symptoms of distress and PTSD at earlier point in time. The variable 'house
      destroyed' was the only factor that was independently related to symptoms of PTSD
      at wave 2. Ten years after the disaster, disaster exposure was mediated by
      symptoms of PTSD at waves 2 and 3. Disaster exposure was not independently
      related to symptoms of PTSD ten years post-disaster. CONCLUSIONS: Until 4 years
      after the disaster, degree of exposure (a sum score) was a risk factor for PTSD
      symptoms while none of the individual disaster experiences could be identified as
      an independent risk factor. Ten years post-disaster, disaster exposure was no
      longer an independent risk factor for symptoms of PTSD. Since symptoms of PTSD
      and distress at earlier waves perpetuate the symptoms at later waves, health care
      workers should aim their resources at those who still have symptoms after one and
      a half year post-disaster, to prevent health problems at medium and long-term.

PMID- 22989094
TI  - Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant
      ovarian cancer patients treated with bevacizumab.
AB  - INTRODUCTION: Anti-VEGF treatment has proven effective in recurrent ovarian
      cancer. However, the identification of the patients most likely to respond is
      still pending. It is well known that the angiogenesis is regulated by several
      other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF)
      system and the fibroblast growth factor (FGF) system. These other signaling
      pathways may remain active or become upregulated during anti-VEGF treatment.The
      aim of the present study was to investigate if potential changes of PDGF-BB, PDGF
      AA, and FGF2 before and during bevacizumab treatment had predictive value for
      early progression or survival. Furthermore, we wanted to investigate the
      importance of serum VEGF in the same cohort. METHODS: This study included 106
      patients with chemotherapy-resistant epithelial ovarian cancer who were treated
      with single agent bevacizumab as part of a biomarker protocol. Patients were
      evaluated for response by the Response Evaluation Criteria In Solid Tumors
      (RECIST) and/ or Gynecologic Cancer Intergroup (GCIG) CA125 criteria. Serum
      samples were collected at baseline and prior to each treatment. FGF2, PDGF-BB,
      PDGF-AA were quantified simultaneously using the Luminex system, and VEGF-A was
      measured by ELISA. Eighty-eight baseline samples were avaliable for FGF2, PDGF
      BB, PDGF-AA analysis, and 93 baseline samples for VEGF. RESULTS: High baseline
      serum VEGF was related to poor overall survival. Furthermore, high serum PDGF-BB
      and FGF2 was of prognostic significance. None of the markers showed predictive
      value, neither at baseline level nor during the treatment.

PMID- 22989095
TI  - Caught in the AKT: identification of a de novo pathway in MCAP and MPPH and its
      therapeutic implications.

PMID- 22989096
TI  - Authors' response to Marras and Oakes, 'Piecing together the puzzle of
      progression and mortality in Parkinson's disease'.

PMID- 22989097
TI  - The Tie2 receptor antagonist angiopoietin-2 in systemic lupus erythematosus: its
      correlation with various disease activity parameters.
AB  - BACKGROUND: Systemic lupus erythematosus is one of the autoimmune diseases
      characterized by multisystem involvement associated with autoantibody and immune
      complex vasculitis along with endothelial cell damage. OBJECTIVE: to study the
      possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory
      and angiogenic mediator in the pathogenesis of SLE and its correlation with the
      state of another inflammatory marker, P-Selectin, as well as with various markers
      of the disease activity. PATIENTS AND METHODS: The present study included 3 main
      groups: active SLE patients (group I), inactive SLE patients (group II) and
      healthy normal control subjects (group III). Groups I and II were subjected to
      disease activity assessment using the SLEDAI scoring system and measurement of
      plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory
      investigations to assess disease activity as: Complete blood count, ESR, serum
      creatinine, C3, C4 and 24-h urinary proteins. RESULTS: The mean level of Plasma
      Ang-2 and P-selectin showed a high significant increase in active group compared
      to inactive SLE patients and control subjects (p < 0.001).There was a significant
      positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h
      urinary proteins in all SLE patients as well as in the active group, and Ang-2
      was a significant independent marker for proteinuria. A significant negative
      correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P
      Selectin showed a high sensitivity and specificity in the patients with SLE.
      CONCLUSION: Our study suggests that Ang-2 may be a more useful marker than P
      Selectin, C3 and C4 in the assessment of disease activity.

PMID- 22989098
TI  - Systemic primary carnitine deficiency: an overview of clinical manifestations,
      diagnosis, and management.
AB  - Systemic primary carnitine deficiency (CDSP) is an autosomal recessive disorder
      of carnitine transportation. The clinical manifestations of CDSP can vary widely
      with respect to age of onset, organ involvement, and severity of symptoms, but
      are typically characterized by episodes of hypoketotic hypoglycemia,
      hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal
      myopathy, elevated creatine kinase (CK), and cardiomyopathy in childhood; or
      cardiomyopathy, arrhythmias, or fatigability in adulthood. The diagnosis can be
      suspected on newborn screening, but is established by demonstration of low plasma
      free carnitine concentration (<5 MUM, normal 25-50 MUM), reduced fibroblast
      carnitine transport (<10% of controls), and molecular testing of the SLC22A5
      gene. The incidence of CDSP varies depending on ethnicity; however the frequency
      in the United States is estimated to be approximately 1 in 50,000 individuals
      based on newborn screening data. CDSP is caused by recessive mutations in the
      SLC22A5 gene. This gene encodes organic cation transporter type 2 (OCTN2) which
      transport carnitine across cell membranes. Over 100 mutations have been reported
      in this gene with the c.136C > T (p.P46S) mutation being the most frequent
      mutation identified. CDSP should be differentiated from secondary causes of
      carnitine deficiency such as various organic acidemias and fatty acid oxidation
      defects. CDSP is an autosomal recessive condition; therefore the recurrence risk
      in each pregnancy is 25%. Carrier screening for at-risk individuals and family
      members should be obtained by performing targeted mutation analysis of the
      SLC22A5 gene since plasma carnitine analysis is not a sufficient methodology for
      determining carrier status. Antenatal diagnosis for pregnancies at increased risk
      of CDSP is possible by molecular genetic testing of extracted DNA from chorionic
      villus sampling or amniocentesis if both mutations in SLC22A5 gene are known.
      Once the diagnosis of CDSP is established in an individual, an echocardiogram,
      electrocardiogram, CK concentration, liver transaminanses measurement, and pre
      prandial blood sugar levels, should be performed for baseline assessment. Primary
      treatment involves supplementation of oral levocarnitine (L-carnitine) at a dose
      of 50-400 mg/kg/day divided into three doses. No formal surveillance guidelines
      for individuals with CDSP have been established to date, however the following
      screening recommendations are suggested: annual echocardiogram and
      electrocardiogram, frequent plasma carnitine levels, and CK and liver
      transaminases measurement can be considered during acute illness. Adult women
      with CDSP who are planning to or are pregnant should meet with a metabolic or
      genetic specialist ideally before conception to discuss management of carnitine
      levels during pregnancy since carnitine levels are typically lower during
      pregnancy. The prognosis for individuals with CDSP depends on the age,
      presentation, and severity of symptoms at the time of diagnosis; however the long
      term prognosis is favorable as long as individuals remain on carnitine
      supplementation.

PMID- 22989099
TI  - Body posture during colour Doppler imaging of the eye and orbit.

PMID- 22989100
TI  - Quercetin improves hepatic fibrosis reducing hepatic stellate cells and
      regulating pro-fibrogenic/anti-fibrogenic molecules balance.
AB  - BACKGROUND AND AIM: Development of hepatic cirrhosis involves oxidative stress,
      inflammation, hepatic stellate cells (HSC)s activation and fibrosis. On the other
      hand, quercetin, a natural flavonoid is a potent antioxidant and activator of
      superoxide dismutase and catalase. The aim was to determinate the effect of
      quercetin on HSCs and development of hepatic fibrosis. METHODS: Wistar male rats
      were chronically intoxicated with CCl(4) for 8 weeks and concomitantly treated
      with 100 mg/kg per day of quercetin. Oxidative state, inflammation and fibrosis
      were evaluated. Effect of quercetin on apoptosis of HSC was determined by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling reaction.
      RESULTS: Sixty percent of reduction in fibrosis index was observed with quercetin
      treatment compared with control animals. Considerable reduction on hepatic
      enzymes was detected in the quercetin group. Expression of pro-fibrotic genes
      (transforming growth factor-beta [TGF-beta], Collagen 1alpha [Col-1alpha] and
      connective tissue growth factor [CTGF]) were decreased by quercetin. Quercetin
      increased gene expression and functional activity of antioxidant enzymes
      superoxide dismutase and catalase. Inflammatory index was highly reduced as
      determined by H-E staining and pro-inflammatory cytokines expression and nuclear
      factor-kappaB activation were also inhibited. A significant reduction of 65% on
      activated HSC number was detected when rats were treated with quercetin.
      Quercetin also induced activation of matrix metalloproteinases MMP2 and MMP9
      contributing to decreased index of fibrosis. CONCLUSIONS: Treatment with
      quercetin reduces oxidation and inflammation and also prevents liver fibrosis,
      through induction of HSC apoptosis and activation of MMPs.

PMID- 22989101
TI  - Giant cell polymyositis and myocarditis associated with myasthenia gravis and
      thymoma.
AB  - We describe an unusual case of myasthenia gravis. Our patient had been diagnosed
      as having myasthenia gravis with thymoma at the age of 64 years, and died of
      acute respiratory failure at the age of 80 years. Post mortem examination
      revealed CD8-positive lymphocytic infiltration with numerous giant cells in the
      skeletal muscles and myocardium. Immunohistochemical and ultrastructural studies
      revealed that there were two types of giant cells: histiocytic and myocytic in
      origin. Furthermore, both types of giant cells were immunopositive for proteins
      implicated in the late endosome and lysosome-protease systems, suggesting that
      endocytosis may be the key mechanism in the formation of giant cells. The present
      case, together with a few similar cases reported previously, may represent a
      particular subset of polymyositis, that is, giant cell polymyositis and
      myocarditis associated with myasthenia gravis and thymoma.

PMID- 22989102
TI  - Effects of polyethylene glycol on DNA adsorption and hybridization on gold
      nanoparticles and graphene oxide.
AB  - Understanding the interface between DNA and nanomaterials is crucial for rational
      design and optimization of biosensors and drug delivery systems. For detection
      and delivery into cells, where high concentrations of cellular proteins are
      present, another layer of complexity is added. In this context, we employ
      polyethylene glycol (PEG) as a model polymer to mimic the excluded volume effect
      of cellular proteins and to test its effects on DNA adsorption and hybridization
      on gold nanoparticles (AuNPs) and graphene oxide (GO), both of which show great
      promise for designing intracellular biosensors and drug delivery systems. We show
      that PEG 20000 (e.g., 4%) accelerates DNA hybridization to DNA-functionalized
      AuNPs by 50-100%, but this enhanced hybridization kinetics has not been observed
      with free DNA. Therefore, this rate enhancement is attributed to the surface
      blocking effect by PEG instead of the macromolecular crowding effect. On the
      other hand, DNA adsorption on citrate-capped AuNP surfaces is impeded even in the
      presence of a trace level (i.e., parts per billion) of PEG, confirming PEG
      competes with DNA for surface binding sites. Additional insights have been
      obtained by studying the adsorption of a thiolated DNA and a peptide nucleic
      acid. In these cases, the steric effects of PEG to impede adsorption are
      observed. Similar observations have also been made with GO. Therefore, PEG may be
      used as an effective blocking agent for both hydrophilic AuNP and for GO that
      also contains hydrophobic domains.

PMID- 22989103
TI  - Tailoring bimetallic alloy surface properties by kinetic control of self
      diffusion processes at the nanoscale.
AB  - Achieving control of the nanoscale structure of binary alloys is of paramount
      importance for the design of novel materials with specific properties, leading
      to, for example, improved reaction rates and selectivity in catalysis, tailored
      magnetic behavior in electronics, and controlled growth of nanostructured
      materials such as graphene. By means of a combined experimental and theoretical
      approach, we show that the complex self-diffusion mechanisms determining these
      key properties can be mostly defined by kinetic rather than energetic effects. We
      explain how in the Ni-Cu system nanoscale control of self-diffusion and
      segregation processes close to the surface can be achieved by finely tuning the
      relative concentration of the alloy constituents. This allows tailoring the
      material functionality and provides a clear explanation of previously observed
      effects involved, for example, in the growth of graphene films and in the
      catalytic reduction of carbon dioxide.

PMID- 22989104
TI  - Characteristics of squamous cell carcinoma in situ of the ear treated using Mohs
      micrographic surgery.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is used to treat squamous cell
      carcinoma in situ (SCCIS) for tissue conservation. OBJECTIVE: To examine
      characteristics of patients with SCCIS of the external ear treated using MMS.
      METHODS: A retrospective review from 2005 to 2011. RESULTS: We identified 173
      cases of SCCIS of the ear. The population was 94% male (p < .01), with a mean age
      of 71. Eight percent (n = 13) of tumors were recurrent after prior treatment.
      Recurrent tumors occurred exclusively in men and were associated with larger
      initial size (p = .05), more layers for clearance p = .059), and larger final
      defect size (p = .01). Tumors with larger initial area were independently
      associated with older age (p < .01). Complexity of repair was independently
      associated with more layers (p < .01), larger initial area (p = .01), and larger
      final area (p = .02). Sex did not affect repair type. CONCLUSION: SCCIS of the
      ear predominantly affects men in our referral base of 85% to 90% private patients
      and 10% to 15% veterans. Recurrent tumors were associated with larger initial
      size and subclinical spread of tumor. Primary tumors on average required 1.6
      layers, validating the utility of MMS in this population in delineating the
      subclinical spread of SCCIS of the ear.

PMID- 22989105
TI  - Micropollutant fate in wastewater treatment: redefining "removal".

PMID- 22989106
TI  - Use of wireless phones and serum beta-trace protein in randomly recruited persons
      aged 18-65 years: a cross-sectional study.
AB  - BACKGROUND: There are studies suggesting effects on sleep from pulse-modulated
      radiofrequency fields used in mobile and cordless phones. So far, reports of
      adverse effects in observational studies are of limited value for risk assessment
      while effects from experimental studies seem to be more consistent but unclear as
      to their importance for health. The aim of this study was to investigate whether
      use of wireless phones is associated with lower concentrations of beta-trace
      protein (lipocalin-type prostaglandin D synthase), a key enzyme in the synthesis
      of prostaglandin D(2), an endogenous sleep-promoting neurohormone. METHODS: Three
      hundred and fourteen people, aged 18-65 years and living in the municipality of
      Orebro, Sweden, were recruited randomly using the population registry. Total and
      age-specific linear regression analyses adjusted for known covariates were used
      to calculate associations between levels of beta-trace protein and short- and
      long-term use of wireless phones. RESULTS: Overall, no statistically significant
      association between use of wireless phones and the serum concentration of beta
      trace protein was found, neither with respect to short-term nor long-term use.
      Age-specific analyses, however, yielded negative associations for long-term use
      (cumulative hours of use) and beta-trace protein in the youngest age group (18-30
      years). CONCLUSION: This study provided no overall evidence of an association
      between wireless phone use and serum concentrations of beta-trace protein. While
      the findings in the 18-30 year age group indicating lower concentrations with
      more cumulative hours of use should be further investigated, no causal inferences
      can be made from the results of the present study.

PMID- 22989107
TI  - Living large: affect amplification in visual perception predicts emotional
      reactivity to events in daily life.
AB  - It was hypothesised that affect-amplifying individuals would be more reactive to
      affective events in daily life. Affect amplification was quantified in terms of
      overestimating the font size of positive and negative, relative to neutral, words
      in a basic perception task. Subsequently, the same (N=70) individuals completed a
      daily diary protocol in which they reported on levels of daily stressors,
      provocations, and social support as well as six emotion-related outcomes for 14
      consecutive days. Individual differences in affect amplification moderated
      reactivity to daily affective events in all such analyses. For example, daily
      stressor levels predicted cognitive failures at high, but not low, levels of
      affect amplification. Affect amplification, then, appears to have widespread
      utility in understanding individual differences in emotional reactivity.

PMID- 22989108
TI  - Population data of six Alu insertions in indigenous groups from Sabah, Malaysia.
AB  - BACKGROUND AND AIM: The present study is the first to report the genetic
      relatedness of indigenous populations of Sabah, Malaysia, using a set of Indel
      markers (HS4.32, TPA25, APO, PV92, B65 and HS3.23). The primary aim was to assess
      the genetic relationships among these populations and with populations from other
      parts of the world by examining the distribution of these markers. SUBJECTS AND
      METHODS: A total of 504 volunteers from the three largest indigenous groups, i.e.
      Kadazan-Dusun, Bajau and Rungus, were recruited for the study. Six Alu insertions
      were typed by PCR with specific primer sets. RESULTS: All insertions were found
      to present at different frequencies, ranging from 0.170-0.970. The heterozygosity
      of most of the markers was high (>0.4), with the exception of HS3.23 and APO. A
      genetic differentiation study revealed that these populations are closely related
      to each other (G(ST) = 0.006). A principle component plot showed that these
      populations have higher affinity to Mainland South East Asia/East Asia
      populations, rather than Island Southeast Asia (ISEA) populations. CONCLUSION: In
      summary, these indigenous groups were closely associated in terms of their
      genetic composition. This finding also supports the colonization model of ISEA,
      which suggests that the inhabitants of this region were mostly descendants from
      Southern China.

PMID- 22989109
TI  - Mycobacterium ulcerans infection: evolution in clinical management.
AB  - Mycobacterium ulcerans causes significant morbidity in various endemic locations
      in Australia and West Africa. The commonest presentation is as a necrotic ulcer
      often with surrounding subcutaneous necrosis and oedema, which can cause
      significant morbidity, deformity and functional impairment. Traditional treatment
      was wide excision and debridement with grafting or flap reconstructions further
      adding to morbidity and with high recurrence rates. Following publication of
      clinical studies where antibiotics were shown to be effective, treatment has
      moved towards combination management with systemic antibiotics and limited
      surgery involving mainly debridement of the ulcers. Identification of the
      'paradoxical' immune-reconstitution syndrome has also impacted upon the extent of
      excision required. This paper will present the evolution in clinical management
      of M. ulcerans cases on the Bellarine Peninsula, Victoria, Australia.

PMID- 22989110
TI  - Preoperative staging of locally advanced bladder cancer before radical cystectomy
      using 3 tesla magnetic resonance imaging with a standardized protocol.
AB  - OBJECTIVE: The correlation between clinical tumour stage and pathological tumour
      stage in radical cystectomy specimens in locally advanced bladder cancer is
      suboptimal. Radiological methods have so far been of limited value in
      preoperative staging; however, the resolution with magnetic resonance imaging
      (MRI) has improved with further technical developments of the method. The aim of
      this study was to compare tumour stage at MRI with pathological tumour stage in
      the cystectomy specimen. MATERIAL AND METHODS: Prospectively, 53 patients with
      invasive bladder cancer were preoperatively investigated with 3 tesla (3T) MRI
      using a standardized protocol. 3T MRI was performed at a standardized bladder
      volume. Clinical tumour stage, tumour stage at MRI and pathological tumour stage
      groups (Ta, Cis, T1/T2a, T2b/T3a, T3b/T4a), were compared, and sensitivity and
      specificity for organ-confined and non-organ-confined disease (stage T3a or above
      or lymph-node metastases) were analysed. RESULTS: MRI overestimated tumour stage
      in 23 out of 47 patients (49%), whereas six patients (13%) were understaged. In
      the three groups of patients (those with the same stage group at MRI as in the
      cystectomy specimen, overestimated tumour stage and understaged patients), the
      time interval between transurethral resection of the bladder (TURB) and MRI did
      not differ significantly. CONCLUSIONS: Preoperative MRI overestimated tumour
      stage in almost half of the patients investigated in this study. Postoperative
      changes could have contributed to such overstaging with MRI.

PMID- 22989111
TI  - Hepatocyte growth factor regulates HLX1 gene expression to modulate HTR-8/SVneo
      trophoblast cells.
AB  - BACKGROUND: Paracrine signaling of the hepatocyte growth factor (HGF) cytokine
      plays an important role in survival and invasion ability of placental
      trophoblasts. However, the intracellular factors and biological pathways
      underlying these responses remain unclear. METHODS: This study investigated
      whether HGF affected the expression of homeobox gene HLX1, which is principally
      expressed in reproductive tissues and in some immune cells, and evaluated the
      implications of such in the HGF-induced human trophoblast cell line HTR-8/SVneo.
      RESULTS: HGF was found to up-regulate both HLX1 mRNA and protein levels.
      Transient transfection of small interfering RNA (siRNA) targeting HLX1 abrogated
      its induction by HGF. Functionally, HLX1 siRNA not only reduced the growth and
      invasion capacities of HTR-8/SVneo cells at the basal level, but also inhibited
      these responses induced by HGF treatment. CONCLUSIONS: HLX1 is an essential
      downstream signaling component of HGF that leads to growth and invasiveness of
      trophoblast cells.

PMID- 22989112
TI  - von Willebrand's disease in Mexico: a pilot study.
AB  - von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder.
      For a long time, it has been said that VWD was absent in some countries due to
      ethnical differences. Information about the prevalence of VWD in Mexico remains
      unclear, owing largely to poor awareness and diagnosis of the disease. The aim of
      this study was to objectively diagnose VWD in a cohort of highly selected Mexican
      patients with a chronic history of bleeding. Mexican Mestizos were recruited
      between July 2010 and August 2011. Included were 133 adult and paediatric
      patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47
      (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3
      VWD. Mean age for female patients was 19.5 years (range 3-44 years) and 18.5
      years (range 4-63 years) for male patients. Mean age at start of bleeding
      symptoms was 8.8 years (range 1-61). The most frequent clinical symptoms were
      epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and
      petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17
      patients (32.1%). Twenty-six women at childbearing age had a history of abnormal
      gynaecological bleeding. Our results clearly demonstrate the presence of VWD in
      Mexican and underscore the importance of a more detailed description of VWD.
      Efforts to increase the awareness and diagnosis of VWD could help in better
      identification of patients with bleeding disorders and lead to early, appropriate
      management with safe and efficacious therapies such as desmopressin and plasma
      concentrates.

PMID- 22989113
TI  - Creation of a binuclear purple copper site within a de novo coiled-coil protein.
AB  - Although various kinds of metal binding proteins have been constructed by de novo
      design, the creation of a binuclear metal binding site remains especially
      challenging. The purple copper site in subunit II of COX, referred to as the
      Cu(A) site, has two copper ions bridged by two Cys residues. We constructed the
      Cu(A) site consisting of two Cys and two His residues in a de novo designed four
      helical coiled-coil protein. The protein bound two copper ions and exhibited a
      purple color, with relatively intense absorption bands at 488 and 530 nm in the
      UV-vis spectrum. The EPR spectrum displayed unresolved hyperfine splittings in
      the g(?) region, which was similar to the native or engineered Cu(A) site with an
      A(~480)/A(~530) > 1. The extended X-ray absorption structure analyses of the
      protein revealed the presence of the Cu(2)S(2) core structure, with two typical
      N(His)-Cu bonds per core at 1.90 A, two S (Cys)-Cu bonds at 2.21 A, and the Cu-Cu
      bond at 2.51 A, which are also characteristic structures of a purple copper site.

PMID- 22989114
TI  - Interactions among alcohol dependence, perinatal common mental disorders and
      violence in couples in rural Vietnam: a cross-sectional study using structural
      equation modeling.
AB  - BACKGROUND: There is increasing recognition that perinatal common mental
      disorders (PCMDs) are prevalent in women in low and lower-middle income countries
      and emerging evidence that PCMDs and alcohol abuse occur in men in these
      settings. Domestic violence is associated with PCMDs in both women and men. The
      aim of this study was to examine the relationships among PCMDs, alcohol abuse and
      domestic violence in couples in a rural, low-income setting. METHODS: A cross
      sectional, population-based study was undertaken in randomly selected communes in
      Ha Nam and Hanoi, Vietnam. All women in the selected study sites who were at
      least 28 weeks pregnant or were mothers of 4 - 6 week old babies in the
      recruitment period were eligible. The husbands of the women who consented to join
      the study were also invited to participate. Data sources were study-specific
      questions and standardised measures: PCMDs were assessed by psychiatrist
      administered Structured Clinical Interviews for DSM IV disorders, and alcohol
      dependence (AD) by the CAGE questionnaire (cut-off of >= 2). Structural Equation
      Modeling was used to test direct, indirect and mutual relationships
      simultaneously in the hypothesised model. RESULTS: In total 364/392 (93%)
      eligible women agreed to participate. Of these, 360 were married, and 230 (64%)
      of their husbands also participated to yield a sample of 230 couples for
      analyses. Overall, in 7.4% (95% CI: 4.6-11.6) of couples both wife and husband
      were diagnosed with a PCMD; and 41.2% (95% CI: 35.1-47.8) of couples at least one
      member had a PCMD. Comorbid PCMD and AD were observed in 6.9% (95% CI: 4.3-11.0)
      of men, but did not occur in women. After controlling for other psychosocial risk
      factors comorbid PCMD and AD in husbands increased by 4.7 times the probability
      of PCMDS in their wives via intimate partner violence. PCMDS in wives did not
      increase the probability of PCMDS or AD in husbands. CONCLUSIONS: These data
      provide evidence that comorbid PCMD and AD in husbands have a significant adverse
      effect on the mental health of their wives in rural areas of Vietnam. This
      indicates that strategies to prevent and treat PCMDs in women will be more
      effective if paired with initiatives to reduce alcohol dependence and violent
      behaviours in men.

PMID- 22989115
TI  - Incomplete transfer of accessory loci influencing SbMATE expression underlies
      genetic background effects for aluminum tolerance in sorghum.
AB  - Impaired root development caused by aluminum (Al) toxicity is a major cause of
      grain yield reduction in crops cultivated on acid soils, which are widespread
      worldwide. In sorghum, the major Al-tolerance locus, AltSB , is due to the
      function of SbMATE, which is an Al-activated root citrate transporter. Here we
      performed a molecular and physiological characterization of various AltSB donors
      and near-isogenic lines harboring various AltSB alleles. We observed a partial
      transfer of Al tolerance from the parents to the near-isogenic lines that was
      consistent across donor alleles, emphasizing the occurrence of strong genetic
      background effects related to AltSB . This reduction in tolerance was variable,
      with a 20% reduction being observed when highly Al-tolerant lines were the AltSB
      donors, and a reduction as great as 70% when other AltSB alleles were
      introgressed. This reduction in Al tolerance was closely correlated with a
      reduction in SbMATE expression in near-isogenic lines, suggesting incomplete
      transfer of loci acting in trans on SbMATE. Nevertheless, AltSB alleles from the
      highly Al-tolerant sources SC283 and SC566 were found to retain high SbMATE
      expression, presumably via elements present within or near the AltSB locus,
      resulting in significant transfer of the Al-tolerance phenotype to the derived
      near-isogenic lines. Allelic effects could not be explained by coding region
      polymorphisms, although occasional mutations may affect Al tolerance. Finally, we
      report on the extensive occurrence of alternative splicing for SbMATE, which may
      be an important component regulating SbMATE expression in sorghum by means of the
      nonsense-mediated RNA decay pathway.

PMID- 22989117
TI  - Characteristics of esophageal proper muscle in patients with non-cardiac chest
      pain using high-frequency intraluminal ultrasound.
AB  - BACKGROUND AND AIM: It is unclear which mechanisms play a predominant role in the
      pathogenesis of esophageal non-cardiac chest pain (NCCP). We aimed to examine the
      features of esophageal proper muscle and esophageal contractility using a high
      frequency intraluminal ultrasound (HFIUS) in patients with NCCP. METHODS: A total
      of 68 patients with NCCP were classified into two groups according to the results
      of typical reflux symptoms and/or esophagogastroduodenoscopy and/or 24-h
      esophageal pH monitoring: gastroesophageal reflux disease (GERD)-positive NCCP (n
      = 34) and GERD-negative NCCP groups (n = 34). Additionally 16 asymptomatic
      healthy subjects were included as controls. Using HFIUS, we analyzed the
      esophageal proper muscle thickness and cross-sectional area (CSA) at 3 cm above
      lower esophageal sphincter (LES) and 9 cm above LES during baseline rest and peak
      contraction periods among the control, GERD-positive NCCP and GERD-negative NCCP
      groups, and examined the completeness of three phases of esophageal action during
      five wet swallows in the three groups. RESULTS: The muscle thickness and CSA
      tended to be larger in GERD-negative NCCP than in GERD-positive NCCP and in
      control groups at esophageal body during both periods. All of the controls and
      patients with GERD-positive NCCP presented the complete peristaltic type.
      Whereas, 11 of 34 patients with GERD-negative NCCP presented the incomplete
      peristaltic type. CONCLUSIONS: Using HFIUS, patients with GERD-negative NCCP had
      increased muscle thickness and CSA. Some GERD-negative NCCP had the incomplete
      peristaltic type.

PMID- 22989118
TI  - Physicians' perspectives on the uncertainties and implications of chromosomal
      microarray testing of children and families.
AB  - Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic
      disorders in pediatric populations, but can produce uncertain and unexpected
      findings. This article explores clinicians' perspectives and identifies
      challenges in effectively interpreting results and communicating with families
      about CMA. Responses to an online survey were obtained from 40 clinicians who had
      ordered CMA. Content included practice characteristics and perceptions, and
      queries about a hypothetical case involving uncertain and incidental findings.
      Data were analyzed using nonparametric statistical tests. Clinicians' comfort
      levels differed significantly for explaining uncertain, abnormal, and normal CMA
      results, with lowest levels for uncertain results. Despite clinical guidelines
      recommending informed consent, many clinicians did not consider it pertinent to
      discuss the potential for CMA to reveal information concerning biological
      parentage or predisposition to late-onset disease, in a hypothetical case. Many
      non-genetics professionals ordering CMA did not feel equipped to interpret the
      results for patients, and articulated needs for education and access to genetics
      professionals. This exploratory study highlights key challenges in the practice
      of genomic medicine, and identifies needs for education, disseminated practice
      guidelines, and access to genetics professionals, especially when dealing with
      uncertain or unexpected findings.

PMID- 22989119
TI  - Temporal occurrence of retinal detachments after cataract surgery.
AB  - PURPOSE: To characterize the temporal occurrence of retinal detachments (RD)
      after cataract surgery. METHODS:   In this retrospective, consecutive case
      series, we reviewed the charts of 798 pseudophakic patients with primary
      rhegmatogenous RD that underwent surgery between 1999 and 2009, at the Center of
      Ophthalmology, University of Cologne, Germany. RESULTS: Twenty-five percent of
      all pseudophakic RDs occurred within 1 year after cataract surgery, 50% within
      3.2 years and 90% within 9.9 years. Risk was increased for at least 11 years. The
      time interval was significantly shorter in vitrectomized eyes (2.49 versus 4.31
      years, p = 0.016). Women showed a statistical trend towards longer time intervals
      (4.72 versus 3.93 years, p = 0.052), whereas myopic patients and different age
      groups showed no significant difference. CONCLUSIONS: After cataract surgery, the
      risk for RD was highest in the beginning and decreased continuously over time.
      However, the risk was increased for at least 11 years. Therefore, most studies
      have underestimated the incidence of RD after cataract surgery.

PMID- 22989122
TI  - To blind or not to blind? That remains the question.

PMID- 22989116
TI  - Critical care considerations in the management of the trauma patient following
      initial resuscitation.
AB  - BACKGROUND: Care of the polytrauma patient does not end in the operating room or
      resuscitation bay. The patient presenting to the intensive care unit following
      initial resuscitation and damage control surgery may be far from stable with
      ongoing hemorrhage, resuscitation needs, and injuries still requiring definitive
      repair. The intensive care physician must understand the respiratory,
      cardiovascular, metabolic, and immunologic consequences of trauma resuscitation
      and massive transfusion in order to evaluate and adjust the ongoing resuscitative
      needs of the patient and address potential complications. In this review, we
      address ongoing resuscitation in the intensive care unit along with potential
      complications in the trauma patient after initial resuscitation. Complications
      such as abdominal compartment syndrome, transfusion related patterns of acute
      lung injury and metabolic consequences subsequent to post-trauma resuscitation
      are presented. METHODS: A non-systematic literature search was conducted using
      PubMed and the Cochrane Database of Systematic Reviews up to May 2012. RESULTS
      AND CONCLUSION: Polytrauma patients with severe shock from hemorrhage and massive
      tissue injury present major challenges for management and resuscitation in the
      intensive care setting. Many of the current recommendations for "damage control
      resuscitation" including the use of fixed ratios in the treatment of trauma
      induced coagulopathy remain controversial. A lack of large, randomized,
      controlled trials leaves most recommendations at the level of consensus, expert
      opinion. Ongoing trials and improvements in monitoring and resuscitation
      technologies will further influence how we manage these complex and challenging
      patients.

PMID- 22989120
TI  - The relationship between nurses' perception of work environment and patient
      satisfaction in adult critical care.
AB  - BACKGROUND: Patient satisfaction in critical care is rarely measured yet has a
      major impact on hospital reimbursement. The critical care setting is
      characterized by high patient acuity and a fast-paced work environment. Nurses'
      perception of work environment in relation to various patient outcomes including
      patient satisfaction has not been explored exclusively in critical care.
      OBJECTIVES: (a) Examine patient's perception of nursing care associated with
      their hospitalization in the intensive care unit. (b) Describe nurses' perception
      of work environment within a defined sample of adult critical care units, using
      the Practice Environment Scale of the Nursing Work Index (PES-NWI). (c) Explore
      the relationships between nurses' perception of work environment and patient
      satisfaction in adult critical care. METHODS: This study used existing data to
      address the study aims. Unit-level comparisons were examined using analysis of
      variance. The final aim was examined using multilevel modeling for longitudinal
      data. RESULTS: Patients were very satisfied with their hospitalization (4.48 out
      of 5.0). Significant differences were noted among all unit level comparisons (p <
      .001). Nurses also reported moderate satisfaction with work environment as
      measured by the PES-NWI, with perception of the role of their nurse manager
      receiving the highest scores. Perception of nurse manager leadership and ability
      was significantly related to patient satisfaction (p= .018). Favorable perception
      of the nurse manager was associated with a .424 point increase in patient
      satisfaction. CONCLUSIONS: This study offers preliminary support for the
      relationship between nurses' perception of work environment and patient
      satisfaction in critical care. It also highlights the pivotal role of the nurse
      manager in both nurse and patient satisfaction. CLINICAL RELEVANCE: This study
      examines two important aspects that are both relevant and important to clinical
      nursing. The first aspect is the healthy work environment. Multiple studies have
      linked the nursing work environment to patient outcomes and this is an area that
      deserves further attention. The second aspect, patient satisfaction, is now
      associated with hospital reimbursement. The relationship between the nursing work
      environment and patient satisfaction highlights an important link to improving
      patient care.

PMID- 22989123
TI  - Conflict in context: designing authentic teamwork education.

PMID- 22989124
TI  - Unsigned: why anonymous evaluations in clinical settings are counterproductive.

PMID- 22989125
TI  - Don't manage the conflict: transform it through collaboration.

PMID- 22989126
TI  - Management of human capital: how can we inspire casual tutors to go the extra
      mile?

PMID- 22989127
TI  - Conflict in medical teams: opportunity or danger?
AB  - OBJECTIVES:   Intragroup conflicts often occur when people are called upon to
      collaborate in the accomplishment of a task. For example, when surgeons and
      nurses work together during an operation, conflicts may emerge because of
      differences in functional understanding. Whether these conflicts are beneficial
      or detrimental to team outcomes has been the source of much debate. From one
      perspective, a conflict that stems from differences in members' functional
      understanding may enhance team members' understanding and performance of the task
      at hand. By contrast, such a conflict may cause hostility, emotionality and
      distraction from actual task accomplishment. METHODS:   This study reviews
      findings on the relationships between intragroup conflict and team outcomes,
      discusses potential conflict resolution strategies for intragroup conflicts and
      explores how these link to the field of medical education. RESULTS:   Three
      primary types of conflict have been distinguished, involving, respectively, task
      , process- and relationship-associated conflict. Both process conflict, or
      conflict about the logistics of task accomplishment, and relationship conflict,
      or conflict about interpersonal incompatibilities, have been shown to detract
      from effective team functioning. Task conflict, or conflict about the content of
      the task itself, is also generally negative for team functioning, but under
      certain conditions its negative effects may be minimised. For example, when teams
      can clearly separate task issues from relationship issues, task conflicts are
      less destructive for team outcomes. However, achieving such a separation in
      practice, and thereby realising the benefits of task conflict, is quite difficult
      to achieve. CONCLUSIONS:   Intragroup conflicts pose a challenge to effective
      team functioning. In the education of medical professionals, effective training
      in conflict management skills and their application to specific team conflict
      dynamics, such as with reference to how to resolve task as opposed to
      relationship conflict, is critical.

PMID- 22989128
TI  - Conducting systematic reviews in medical education: a stepwise approach.
AB  - OBJECTIVES: As medical education research continues to proliferate, evidence
      syntheses will become increasingly important. The purpose of this article is to
      provide a concise and practical guide to the conduct and reporting of systematic
      reviews. RESULTS:   (i) Define a focused question addressing the population,
      intervention, comparison (if any) and outcomes. (ii) Evaluate whether a
      systematic review is appropriate to answer the question. Systematic and non
      systematic approaches are complementary; the former summarise research on focused
      topics and highlight strengths and weaknesses in existing bodies of evidence,
      whereas the latter integrate research from diverse fields and identify new
      insights. (iii) Assemble a team and write a study protocol. (iv) Search for
      eligible studies using multiple databases (MEDLINE alone is insufficient) and
      other resources (article reference lists, author files, content experts). Expert
      assistance is helpful. (v) Decide on the inclusion or exclusion of each
      identified study, ideally in duplicate, using explicitly defined criteria. (vi)
      Abstract key information (including on study design, participants, intervention
      and comparison features, and outcomes) for each included article, ideally in
      duplicate. (vii) Analyse and synthesise the results by narrative or quantitative
      pooling, investigating heterogeneity, and exploring the validity and assumptions
      of the review itself. In addition to the seven key steps, the authors provide,
      information on electronic tools to facilitate the review process, practical tips
      to facilitate the reporting process and an annotated bibliography.

PMID- 22989129
TI  - Perceptions of job satisfaction relating to affective organisation commitment.
AB  - OBJECTIVES: Affective organisation commitment, which refers to a psychological
      attachment to, and involvement with, an employing institution, is regarded as
      important because of its effects on employee identification with the employer and
      its causal effects on work effort and staff retention. This paper explores the
      experiences of casual tutors facilitating problem-based learning (PBL) tutorials
      and aims to identify aspects of their role that strengthen and detract from
      employee job satisfaction and affective commitment. METHODS: Qualitative data
      were gathered from first- and second-year tutors (N = 13) through 2 focus groups.
      Both clinicians and non-clinicians were recruited, including highly experienced
      staff and those with < 12 months of tutoring experience. RESULTS: Four main
      themes arose from inductive analysis of data: job-related factors; job
      involvement characteristics; professional challenges and responsibilities, and
      mentoring for learning and support. The first 2 themes are congruent with
      previous literature on organisation commitment; novel findings include the
      supportive and compensatory nature of the collegial relationships formed between
      casual tutors. Role attenuation, a job-related factor, was a predominant
      perception as it related to dysfunctional groups and increasing student
      disengagement with PBL. CONCLUSIONS: Within the unique learning environment of
      PBL, positive factors relating to job satisfaction may have an important role to
      play in improving tutors' commitment to their employing organisation. Aspects of
      the role which are viewed most negatively and relate most significantly to
      affective commitment need to be addressed promptly. Attention should be directed
      to supporting tutors to maximise the perceived benefits and providing
      professional development and improved communication to better address issues
      associated with difficult or disengaged students as well as isolation from
      decision-makers.

PMID- 22989130
TI  - Phenomenological analysis of patient experiences of medical student teaching
      encounters.
AB  - CONTEXT: It is important to know how patients are affected by becoming
      opportunistically involved in medical student education. In previous studies,
      researchers rather than patients set the research agenda and expert patients or
      people well known to teachers were more often involved than ordinary people.
      OBJECTIVES: This study aimed to explore how ordinary patients experience
      undergraduate medical teaching when they become involved in it opportunistically
      and to derive practical insights from the lived experiences of these patients.
      METHODS: The research was conducted in line with a conceptual orientation towards
      communities of practice theory and used phenomenology as a way of exploring
      patients' lived experiences in depth. Minimally structured interviews were
      carried out with 10 patients following ordinary out-patient or general practice
      appointments in which students were being taught. Template analysis was used to
      generate provisional themes and a process of phenomenological reduction was used
      to distil individual respondents' lived experiences to their essence. RESULTS:
      The presence of students in ambulatory consultations was normal. Nine respondents
      described transactional relationships in which they remained outside the
      community of practice of which the doctor and student were members. Only an
      intimate problem would engage them deeply enough for a student's presence to
      'bother' them. One patient's personal and professional background led her to
      regard doctors' handling of consultation dynamics as factors contributing to
      whether teaching consultations were negative or positive experiences. When
      doctors' sensitive and inclusive behaviour drew her into a triadic relationship
      with the student and doctor, she experienced mutual benefits with students. When
      it did not, she felt objectified and alienated. CONCLUSIONS: Provided they
      receive the clinical care for which they are attending a consultation and are
      treated respectfully, patients may sometimes willingly become 'objects' from
      which students learn. They may, however, become more deeply engaged in teaching
      consultations in which they participate actively in a triadic relationship of
      mutual benefit with a doctor and student. Teaching consultations call for doctors
      to be sensitive and adaptable.

PMID- 22989131
TI  - Using marketing research concepts to investigate specialty selection by medical
      students.
AB  - OBJECTIVES: This study was intended to examine whether a marketing research
      approach improves understanding of medical specialty selection by medical
      students. This approach likens students to consumers who are deciding whether or
      not to purchase a product (specialty). This approach proposes that when
      consumers' criteria match their perceptions of a product's features, the
      likelihood that they will purchase it (select the specialty) increases. This
      study examines whether exploring students' selection criteria and perceptions of
      various specialties provides additional insights into the selection process.
      METHODS: Using a consumer behaviour model as a framework, a questionnaire was
      designed and administered to Year 6 (final-year) students in 2008 and 2009 to
      elicit information on their knowledge about and interests in various specialties,
      the criteria they used in specialty selection, and their perceptions of six
      specialties. RESULTS: A total of 132 (67%) questionnaires were returned. In many
      instances, consistency between selection criteria and perceptions of a specialty
      was accompanied by interest in pursuing the specialty. Exceptions were noted and
      pointed to areas requiring additional research. For example, although > 70% of
      female students replied that the affordance of a controllable lifestyle was an
      important selection criterion, many were interested in obstetrics and gynaecology
      despite the fact that it was not perceived as providing a controllable lifestyle.
      Minimal overlap among students reporting interest in primary specialties that
      possess similar characteristics (e.g. paediatrics and family medicine)
      demonstrated the need to target marketing (recruitment) efforts for each
      specialty individually. CONCLUSIONS: Using marketing research concepts to examine
      medical specialty selection may precipitate a conceptual shift among health care
      leaders which acknowledges that, to attract students, specialties must meet
      students' selection criteria. Moreover, if consumers (students) deem a product
      (specialty) unattractive, it may need to be examined further to improve its
      appeal.

PMID- 22989132
TI  - Payback time: the associations of debt and income with medical student career
      choice.
AB  - CONTEXT: With impending health care reform in the USA, there is an imperative to
      increase the number of students choosing primary care (PC) careers. Research is
      needed to better understand the roles of economic factors in medical student
      career choice. The objective of this study was to examine the relationships among
      debt, income and career choice by comparing students planning PC careers with
      those aspiring to one of the 12 non-PC fields in which median income exceeds
      US$300 000 ('high-paying non-primary care' [HPNPC]). METHODS: Surveys (response
      rate = 81%) were administered to Year 1 students scheduled to graduate between
      1996 and 2012, and Year 4 students graduating between 1993 and 2010. Respondents
      were students at New York Medical College and East Carolina University's Brody
      School of Medicine. Analyses focused on the 2674 Year 1 respondents choosing a PC
      (n = 1437, 54%) or HPNPC (n = 1237, 46%) career, and the 2307 Year 4 respondents
      intending to pursue PC (n = 992, 43%) or HPNPC (n = 1315, 57%). Longitudinal
      analyses examining changes in career goals during medical school were based on
      students who completed surveys in both Years 1 and 4. The outcome measures
      studied were self-reported debt, anticipated income and self-rated value placed
      on income. RESULTS: Relative to their PC counterparts, students intending to
      pursue HPNPC careers anticipated an average of US$24 904 (Year 4 students) or
      US$29 237 (Year 1 students) greater debt, placed a higher importance value on
      income, and anticipated earning an average of US$58 463 (Year 1 students) and
      US$89 909 (Year 4 students) more in annual income after graduation. Debt was
      associated with the value placed on income in the choice of career and the amount
      of future income anticipated. Students who valued income highly were especially
      inclined to switch from PC during medical school. The switch away from PC was
      associated with debt, as well as with a marked increase in anticipated income.
      CONCLUSIONS: Debt and anticipated income are important concerns which may shape
      future supplies of PC doctors.

PMID- 22989133
TI  - Patients as educators: the challenges and benefits of sharing experiences with
      students.
AB  - CONTEXT: Despite movement towards active patient involvement in the education of
      health professionals, explorations of the experiences of patient-educators beyond
      descriptive research are limited. OBJECTIVES: The purpose of this study was to
      identify the positive and negative factors that contributed to the experiences of
      patient-educators in a health mentors programme for health professional students
      at a Canadian university. METHODS:   Semi-structured focus group discussions and
      individual interviews were used to elicit the experiences of 30 patient-educators
      with chronic conditions or disabilities, of the 151 involved in the programme.
      Thematic analysis was used to identify key themes in the participants'
      experiences. RESULTS: Study participants spoke of the potential challenges and
      benefits of sharing their experiences. The main challenge involved in sharing
      their experiences was potential vulnerability should students not appreciate what
      was shared. The main benefits were personal learning and making valued
      contributions. Two factors influenced the participants' sense of whether the
      potential benefits outweighed the challenges of personal sharing in the
      programme: monitoring disclosure, and perceived student learning. Participants
      used the strategy of monitoring their disclosure to limit how much personal
      information they shared with students. The benefits of participating in the
      programme outweighed the potential challenges when students were seen to embrace
      the intended messages of the patient-educators. CONCLUSIONS: The results of this
      study provide a conceptual framework that can be used to better prepare patient
      educators and students for more reciprocal learning interaction.

PMID- 22989134
TI  - Vicarious learning during simulations: is it more effective than hands-on
      training?
AB  - CONTEXT: Doctor-patient communication skills are often fostered by using
      simulations with standardised patients (SPs). The efficiency of such experiences
      is greater if student observers learn at least as much from the simulation as do
      students who actually interact with the patient. OBJECTIVES: This study aimed to
      investigate whether the type of simulation-based learning (learning by doing
      versus vicarious learning) and the order in which these activities are carried
      out (learning by doing -> vicarious learning versus vicarious learning ->
      learning by doing) have any effect on the acquisition of knowledge on effective
      doctor-patient communication strategies. In addition, we wished to examine the
      extent to which an observation script and a feedback formulation script affect
      knowledge acquisition in this domain. METHODS: The sample consisted of 200
      undergraduate medical students (126 female, 74 male). They participated in two
      separate simulation sessions, each of which was 30 minutes long and was followed
      by a collaborative peer feedback phase. Half of the students first performed
      (learning by doing) and then observed (vicarious learning) the simulation, and
      the other half participated in the reverse order. Knowledge of doctor-patient
      communication was measured before, between and after the simulations. RESULTS:
      Vicarious learning led to greater knowledge of doctor-patient communication
      scores than learning by doing. The order in which vicarious learning was
      experienced had no influence. The inclusion of an observation script also enabled
      significantly greater learning in students to whom this script was given compared
      with students who were not supported in this way, but the presence of a feedback
      script had no effect. CONCLUSIONS: Students appear to learn at least as much, if
      not more, about doctor-patient communication by observing their peers interact
      with SPs as they do from interacting with SPs themselves. Instructional support
      for observing simulations in the form of observation scripts facilitates both
      vicarious learning and learning by doing. An observation script may focus
      learners' attention on the important aspects of doctor-patient communication and
      increase the content-related accuracy of peer feedback.

PMID- 22989135
TI  - Medical misconduct in Hong Kong: implications for medical education around the
      world.
AB  - CONTEXT: Medical educators emphasise responses to medical misconduct, but little
      is known about medical misconduct and its implications for medical education.
      This article investigates the nature of medical malpractice in Hong Kong and
      offers guidance for the inclusion of a curriculum to prevent the occurrence of
      medical misconduct in medical education around the world. METHODS: A
      comprehensive review of judgements made by the Medical Council of Hong Kong
      during the period from July 2008 to December 2010 was conducted. Each of the 40
      cases of inquiry related to medical misconduct were summarised and analysed
      according to 14 factors. RESULTS: Of the 40 cases, nearly half involved only one
      or two charges. The Council found the defendants guilty of professional
      misconduct on 148 of 169 charges, and ordered the following four types of
      penalty: removal order, suspension, warning letter, and reprimand. Cases are
      grouped into three categories involving: improper documentation, inappropriate
      management or prescription of drugs, and failure to interact appropriately with
      patients. The relevant ethical codes or legislation for each category are
      illustrated. CONCLUSIONS: Various types of medical misconduct unquestionably
      caused suffering to the patients involved, their families and society. Hence, it
      is crucial for medical educators to teach students about the importance of
      medical ethics and the prevention of misconduct.

PMID- 22989136
TI  - Setting standards: quality in accreditation.

PMID- 22989137
TI  - Going beyond 'received and understood' as a way of conceptualising feedback.

PMID- 22989139
TI  - An ICF-CY-based content analysis of the Vineland Adaptive Behavior Scales-II.
AB  - BACKGROUND: The International Classification of Functioning, Disability and
      Health (ICF), and its version for children and youth (ICF-CY), has been
      increasingly adopted as a system to describe function and disability. A content
      analysis of the Vineland Adaptive Behavior Scales-II (VABS-II) was conducted to
      examine congruence with the functioning and disability component of this
      framework. METHOD: The 383 VABS-II items contained a total of 1,231 concepts.
      Established linking rules were used to map these concepts to ICF-CY codes.
      RESULTS: Overall the VABS-II concepts were well represented in the ICF-CY. Most
      of the concepts mapped to activity codes; however, about 30% of concepts were
      coded as body function. Most concepts represented relatively discrete activities,
      with more limited coverage of broader categories often included in measures of
      participation. CONCLUSIONS: The VABS-II content maps well to the ICF-CY
      activity/participation codes. Although VABS-II items ask about typical
      performance, item requirements often imply specific means of performance.

PMID- 22989138
TI  - Omega 3 polyunsaturated fatty acid improves spatial learning and hippocampal
      peroxisome proliferator activated receptors (PPARalpha and PPARgamma) gene
      expression in rats.
AB  - BACKGROUND: This study examined the effects of dietary polyunsaturated fatty
      acids (PUFA) as different n-6: n-3 ratios on spatial learning and gene expression
      of peroxisome- proliferator-activated receptors (PPARs) in the hippocampus of
      rats. Thirty male Sprague-Dawley rats were randomly allotted into 3 groups of ten
      animals each and received experimental diets with different n-6: n-3 PUFA ratios
      of either 65:1, 22:1 or 4.5:1. After 10 weeks, the spatial memory of the animals
      was assessed using the Morris Water Maze test. The expression of PPARalpha and
      PPARgamma genes were determined using real-time PCR. RESULTS: Decreasing dietary
      n-6: n-3 PUFA ratios improved the cognitive performance of animals in the Morris
      water maze test along with the upregulation of PPARalpha and PPARgamma gene
      expression. The animals with the lowest dietary n-6: n-3 PUFA ratio presented the
      highest spatial learning improvement and PPAR gene expression. CONCLUSION: It can
      be concluded that modulation of n-6: n-3 PUFA ratios in the diet may lead to
      increased hippocampal PPAR gene expression and consequently improved spatial
      learning and memory in rats.

PMID- 22989140
TI  - Localization of CHMP2B-immunoreactivity in the brainstem of Lewy body disease.
AB  - Alpha-synuclein (alphaS) is one of the major constituents of Lewy bodies (LBs).
      Several lines of evidence suggest that the autophagy-lysosome pathway (ALP) is
      involved in the removal of alphaS. We have previously reported that
      granulovacuolar degeneration (GVD) in neurons involved a subunit of the endosomal
      sorting complexes required for transport (ESCRT). In this study, we examined the
      association between alpha-synucleinopathy and autophagy through
      immunohistochemical analysis of charged multivesicular body protein 2B (CHMP2B),
      a component of the ESCRT-pathway. We examined the brainstems of 17 patients with
      Parkinson's disease (PD), incidental Lewy body disease (ILBD), multiple system
      atrophy (MSA), and Alzheimer's disease (AD) immunohistochemically using
      antibodies against phosphorylated alphaS (palphaS), phosphorylated tau and
      CHMP2B. LBs and a proportion of glial cytoplasmic inclusions (GCIs) were
      immunopositive for palphaS and CHMP2B. Neurons containing CHMP2B-immunoreactive
      granules were detected in PD and ILBD, but not in MSA and AD brains. CHMP2B
      immunoreactivity was increased in the dorsal motor nucleus of the vagus nerve
      (DMNX) in PD and ILBD brains, relative to that in MSA and AD. These findings
      indicate that the ESCRT-pathway is implicated in the formation of alphaS
      inclusions, especially in PD and ILBD.

PMID- 22989141
TI  - Conjunction of chirality and slow magnetic relaxation in the supramolecular
      network constructed of crossed cyano-bridged Co(II)-W(V) molecular chains.
AB  - The addition of chiral 2,2'-(2,6-pyridinediyl)bis(4-isopropyl-2-oxazoline) (iPr
      Pybox) to a self-assembled Co(II)-[W(V)(CN)(8)] magnetic system gives two
      enantiomorphic cyano-bridged chains, {[Co(II)((S,S)-iPr
      Pybox)(MeOH)](3)[W(V)(CN)(8)](2).5.5MeOH.0.5H(2)O}(n) (1-SS) and {[Co(II)((R,R)
      iPr-Pybox) (MeOH)](3)[W(V)(CN)(8)](2).5.5MeOH.0.5H(2)O}(n) (1-RR). Both compounds
      crystallize with a structure containing a unique crossed arrangement of one
      dimensional chains that form a microporous supramolecular network with large
      channels (14.9 A * 15.1 A * 15.3 A) filled with methanol. The investigated
      materials exhibited optical chirality, as confirmed by natural circular dichroism
      and UV-vis absorption spectra. 1-(SS) and 1-(RR) are paramagnets with cyano
      mediated Co(II)-W(V) magnetic couplings that lead to a specific spin arrangement
      with half of the W(V) ions coupled ferromagnetically with their Co(II) neighbors
      and the other half coupled antiferromagnetically. Significant magnetic anisotropy
      with the easy axis along the [101] direction was confirmed by single-crystal
      magnetic studies and can be explained by the single-ion anisotropy of elongated
      octahedral Co(II) sites. Below 3 K, the frequency-dependent chi(M)"(T) signal
      indicated slow magnetic relaxation characteristic of single-chain magnets.

PMID- 22989142
TI  - Protein sorption to charged microgels: characterizing binding isotherms and
      driving forces.
AB  - We present a set of Langmuir binding models in which electrostatic cooperativity
      effects to protein sorption is incorporated in the spirit of Guoy-Chapman-Stern
      models, where the global substrate (microgel) charge state is modified by bound
      reactants (charged proteins). Application of this approach to lysozyme sorption
      to oppositely charged core-shell microgels allows us to extract the intrinsic,
      binding affinity of the protein to the gel, which is salt concentration
      independent and mostly hydrophobic in nature. The total binding affinity is found
      to be mainly electrostatic in nature, changes many orders of magnitude during the
      sorption process, and is significantly influenced by osmotic deswelling effects.
      The intrinsic binding affinity is determined to be about 7 k(B)T for our system.
      We additionally show that Langmuir binding models and those based on excluded
      volume interactions are formally equivalent for low to moderate protein packing,
      if the nature of the bound state is consistently defined. Having appreciated
      this, a more quantitative interpretation of binding isotherms in terms of
      separate physical interactions is possible in the future for a wide variety of
      experimental approaches.

PMID- 22989143
TI  - Management of median lower lip fissures.

PMID- 22989144
TI  - The contribution of stimulus-driven and goal-driven mechanisms to feature-based
      selection in patients with spatial attention deficits.
AB  - When people search a display for a target defined by a unique feature, fast
      saccades are predominantly stimulus-driven whereas slower saccades are primarily
      goal-driven. Here we use this dissociative pattern to assess whether feature
      based selection in patients with lateralized spatial attention deficits is
      impaired in stimulus-driven processing, goal-driven processing, or both. A group
      of patients suffering from extinction or neglect after parietal damage, and a
      group of healthy, age-matched controls, were instructed to make a saccade to a
      uniquely oriented target line which was presented simultaneously with a
      differently oriented distractor line. We systematically varied the salience of
      the target and distractor by changing the orientation of background elements, and
      used a time-based model to extract stimulus-driven (salience) and goal-driven
      (target set) components of selection. The results show that the patients
      exhibited reduced stimulus-driven processing only in the contralesional
      hemifield, while goal-driven processing was reduced across both hemifields.

PMID- 22989145
TI  - A reconfigurable NAND/NOR genetic logic gate.
AB  - BACKGROUND: Engineering genetic Boolean logic circuits is a major research theme
      of synthetic biology. By altering or introducing connections between genetic
      components, novel regulatory networks are built in order to mimic the behaviour
      of electronic devices such as logic gates. While electronics is a highly
      standardized science, genetic logic is still in its infancy, with few agreed
      standards. In this paper we focus on the interpretation of logical values in
      terms of molecular concentrations. RESULTS: We describe the results of
      computational investigations of a novel circuit that is able to trigger specific
      differential responses depending on the input standard used. The circuit can
      therefore be dynamically reconfigured (without modification) to serve as both a
      NAND/NOR logic gate. This multi-functional behaviour is achieved by a) varying
      the meanings of inputs, and b) using branch predictions (as in computer science)
      to display a constrained output. A thorough computational study is performed,
      which provides valuable insights for the future laboratory validation. The
      simulations focus on both single-cell and population behaviours. The latter give
      particular insights into the spatial behaviour of our engineered cells on a
      surface with a non-homogeneous distribution of inputs. CONCLUSIONS: We present a
      dynamically-reconfigurable NAND/NOR genetic logic circuit that can be switched
      between modes of operation via a simple shift in input signal concentration. The
      circuit addresses important issues in genetic logic that will have significance
      for more complex synthetic biology applications.

PMID- 22989146
TI  - Abdominal obesity has the highest impact on metabolic profile in an overweight
      African population.
AB  - AIM: The aim of this study was to determine the association between different
      anthropometric parameters and metabolic profile in an overweight, adult, black
      Kenyan population. METHODS: An opportunity sample of 245 overweight adult Kenyans
      (body mass index (BMI) >= 25 kg/m(2)) was analysed. A score of metabolic profile
      (metabolic Z-score) was constructed on the basis of levels of plasma lipids,
      blood pressure, blood glucose and serum insulin. Linear regressions using
      metabolic Z-score as outcome and six anthropometric variables (waist
      circumference (WC), hip circumference, visceral adipose tissue (VAT), abdominal
      subcutaneous adipose tissue, arm fat area and arm muscle area) separately as
      independent variables were carried out. RESULTS: Mean age of study participants
      was 42.1 years (SD = 9.6) and 26.5% of the participants were men. The median BMI
      was 28.6 kg/m(2) (Q1 = 26.3; Q3 = 31.3). Of the six anthropometric variables
      tested, WC and VAT thickness had the strongest negative association with the
      metabolic profile (beta = 0.17 (0.09; 0.24) and 0.15 (0.08; 0.23), respectively).
      CONCLUSIONS: WC and VAT thickness were the strongest anthropometric predictors
      for the metabolic profile in overweight adult Kenyans. WC is useful in clinical
      practice for the diagnosis of metabolically unhealthy fat accumulation in an
      African setting.

PMID- 22989147
TI  - Utility of 18-fluorodeoxyglucose positron emission/computed tomography in the
      management of recurrent colorectal cancer.
AB  - BACKGROUND: This study aimed to evaluate the utility of 18-fluorodeoxyglucose
      positron emission/computed tomography (PET/CT) in the management of colorectal
      cancer (CRC) patients with suspected recurrence. METHODS: Clinical and imaging
      histories of CRC patients who underwent PET/CT at our institution between 1 April
      2007 and 31 August 2008 for evaluation of recurrent disease were retrospectively
      reviewed. Patients were divided into two groups - (A) patients evaluated for
      suspected local recurrence (based on conventional imaging) and (B) patients with
      carcinoembryonic antigen (CEA) levels in excess of 5 ng/mL; in whom conventional
      imaging was either normal or equivocal. Sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) were derived using
      either histopathology or follow-up imaging as the standard of reference. RESULTS:
      In group A (n = 44), the sensitivity, specificity, PPV, NPV and accuracy of
      PET/CT were 100% (95% confidence interval (CI): 86.7-100), 84.2% (95% CI: 62.4
      94.5), 89.3% (95% CI: 72.8-96.3), 100% (95% CI: 80.6-100) and 93.2%,
      respectively. In group B (n = 18), the sensitivity, specificity, PPV and NPV of
      PET/CT were 76.9% (95% CI: 49.7-91.8), 60.0%, (95% CI: 23.1-88.2), 83.3% (95% CI:
      55.2-95.3) and 50% (95% CI: 18.8-81.2), respectively. CONCLUSION: PET/CT has high
      accuracy in the assessment of local recurrence, particularly with regard to its
      NPV. PET/CT is useful for problem solving in cases of unexplained elevated CEA
      levels.

PMID- 22989148
TI  - Spontaneously published illness stories on a website for young women with breast
      cancer: do writers and themes reflect the wider population?
AB  - This study examined writer characteristics and themes written about in a set of
      167 spontaneously published stories on a Dutch website for young women with
      breast cancer. The stories were coded for 6 disease characteristics and 16
      themes. Coding results were compared with the characteristics of young women with
      breast cancer in a hospital cancer register and to the frequency of problems
      among young breast cancer patients participating in quantitative studies. We
      found that writer characteristics were diverse. Yet, logistic regression showed
      that women were more likely to be a writer if they were diagnosed at a younger
      age (OR 0.82; 95% CI (0.78, 0.85)), underwent a mastectomy (OR 4.63; 95% CI
      (2.59, 8.26)), or were in the first treatment period (OR 2.83; 95% CI (1.44,
      5.58)). All 16 themes were present in the stories, but some themes were addressed
      less often than their frequency among participants of quantitative studies
      suggested. The findings indicate that a set of spontaneously published stories
      might not completely reflect the characteristics and themes of the wider
      population of young women with breast cancer. Websites with spontaneously
      published stories should inform readers about this.

PMID- 22989149
TI  - Changes in physical activity levels, lesson context, and teacher interaction
      during physical education in culturally and linguistically diverse Australian
      schools.
AB  - BACKGROUND: Recent data show that only 15% of Australian adolescents participate
      in adequate amounts of physical activity (PA) and those students from Asian and
      Middle-Eastern backgrounds in Grades 6-12 are significantly less active than
      their English-speaking background peers. Schools have recently been recognised as
      the most widely used and cost-effective setting for promoting PA among youth and
      one domain within schools where PA can occur regularly for all youth, regardless
      of cultural background or socio-economic status, is during physical education
      (PE). METHODS: This study describes changes in physical activity (PA), lesson
      context and teacher interaction in physical education over the first two years in
      culturally and linguistically diverse secondary schools. Grade 7 PE classes in
      six schools were randomly observed using systematic direct observation (n = 81)
      and then followed up over the same period (n = 51) twelve months later. RESULTS:
      There was no significant decline in moderate-to-vigorous physical activity (MVPA)
      during PE (MD = -4.8%; p = .777), but a significant decline and medium negative
      effect in time spent in vigorous physical activity (VPA) (MD = -7.9%; p = .009)
      during PE was observed. Significant declines and large negative effects over time
      in percentage of PE time spent in management (MD = -8.8%; p < .001) and the
      number of observations where teachers promoted PA (MD = -20.7%; p < .001).
      CONCLUSIONS: The decline of VPA and teacher promotion of PA in culturally and
      linguistically diverse schools is of concern. Given the declines in VPA and the
      increases in time spent in game play, further research is needed to ascertain
      whether PE instruction could be improved by focussing on skill instruction and
      fitness in a games-based PE instruction model. Further research for increasing
      teacher promotion of PA during PE is needed.

PMID- 22989150
TI  - Initial symptoms and delay in patients with penile carcinoma.
AB  - OBJECTIVE: This study aimed to assess initial symptoms and factors associated
      with patients' and doctors' delay in penile carcinoma. MATERIAL AND METHODS:
      Fifty consecutive patients with penile carcinoma treated with an organ-sparing
      technique and nine with partial amputation were enrolled in a prospective study
      at the Department of Urology, Orebro University Hospital, between 2005 and 2009.
      Face-to-face structured interviews in combination with self-assessment forms were
      used for the patients' descriptions of clinical symptoms, treatment seeking and
      reasons for delay. Data were also extracted from the medical records confirming
      time-lag between GP assessment, specialist care and time for diagnosis. RESULTS:
      Erythema, rash and eczema were the most common initial symptoms (35%). In total,
      65% had a patients' delay of more than 6 months, and among these there was a
      small, but not statistically significant, predominance for pT1 and pTis tumours.
      Living with a stable partner did not affect the delay. The most common reason for
      patients' delay was the feeling of embarrassment over symptoms localized in a
      sexual body area. Nine patients had a doctors' delay of more than 3 months from
      first special visit to diagnosis. Eight of these patients consulted
      dermatologists and were subjected to repeated biopsies, leaving premalignant
      results. CONCLUSIONS: A considerable proportion of the patients had a patients'
      delay of more than 6 months, perhaps due to benign initial symptoms as erythema,
      rash or eczema. Psychological factors such as embarrassment and denial may also
      be involved, as well as insufficient awareness or knowledge.

PMID- 22989151
TI  - Towards a Universal SMILES representation - A standard method to generate
      canonical SMILES based on the InChI.
AB  - BACKGROUND: There are two line notations of chemical structures that have
      established themselves in the field: the SMILES string and the InChI string. The
      InChI aims to provide a unique, or canonical, identifier for chemical structures,
      while SMILES strings are widely used for storage and interchange of chemical
      structures, but no standard exists to generate a canonical SMILES string.
      RESULTS: I describe how to use the InChI canonicalisation to derive a canonical
      SMILES string in a straightforward way, either incorporating the InChI
      normalisations (Inchified SMILES) or not (Universal SMILES). This is the first
      description of a method to generate canonical SMILES that takes stereochemistry
      into account. When tested on the 1.1 m compounds in the ChEMBL database, and a 1
      m compound subset of the PubChem Substance database, no canonicalisation failures
      were found with Inchified SMILES. Using Universal SMILES, 99.79% of the ChEMBL
      database was canonicalised successfully and 99.77% of the PubChem subset.
      CONCLUSIONS: The InChI canonicalisation algorithm can successfully be used as the
      basis for a common standard for canonical SMILES. While challenges remain - such
      as the development of a standard aromatic model for SMILES - the ability to
      create the same SMILES using different toolkits will mean that for the first time
      it will be possible to easily compare the chemical models used by different
      toolkits.

PMID- 22989152
TI  - Hypercalciuria and kidney function in children with haemophilia.
AB  - Adults with haemophilia have a higher incidence of chronic kidney disease than
      general male population. We recently showed that children with haemophilia have
      higher urinary calcium excretion and lower whole body bone mineral density than
      controls in spite of prophylaxis with the deficient coagulation factor
      concentrate, serum vitamin D concentrations comparable to those of healthy
      children and physically active lifestyle. Persistent hypercalciuria may result in
      nephrocalcinosis and impact renal function. This study sought to assess
      persistence of urinary calcium excretion and kidney function in children with
      haemophilia. We investigated retrospectively urinary calcium excretion in 30
      children with haemophilia (mean age 12.5 years) from consecutive urine samples
      over a 2-year period. Renal evaluation included blood and urine specimen, blood
      pressure, and renal ultrasound. High number of children with haemophilia had
      intermittent hypercalciuria. Hypercalciuria was not associated with age, severity
      of haemophilia or previous hypercalciuria. Kidney function and renal ultrasound
      were normal with the exception of suspected kidney stone in one patient with
      haemophilia and transient hypercalciuria. Vitamin D concentrations improved after
      the families had received information and recommendations concerning vitamin D
      substitution. Our findings indicate that haemophilia per se predisposes to
      hypercalciuria which may in turn affect bone mineral content and kidney function.
      Whether childhood-onset intermittent hypercalciuria contributes to hypertension
      and renal complications in adulthood remains to be elucidated in future studies.

PMID- 22989154
TI  - LAMBADA and InflateGRO2: efficient membrane alignment and insertion of membrane
      proteins for molecular dynamics simulations.
AB  - At the beginning of each molecular dynamics membrane simulation stands the
      generation of a suitable starting structure which includes the working steps of
      aligning membrane and protein and seamlessly accommodating the protein in the
      membrane. Here we introduce two efficient and complementary methods based on pre
      equilibrated membrane patches, automating these steps. Using a voxel-based cast
      of the coarse-grained protein, LAMBADA computes a hydrophilicity profile-derived
      scoring function based on which the optimal rotation and translation operations
      are determined to align protein and membrane. Employing an entirely geometrical
      approach, LAMBADA is independent from any precalculated data and aligns even
      large membrane proteins within minutes on a regular workstation. LAMBADA is the
      first tool performing the entire alignment process automatically while providing
      the user with the explicit 3D coordinates of the aligned protein and membrane.
      The second tool is an extension of the InflateGRO method addressing the
      shortcomings of its predecessor in a fully automated workflow. Determining the
      exact number of overlapping lipids based on the area occupied by the protein and
      restricting expansion, compression and energy minimization steps to a subset of
      relevant lipids through automatically calculated and system-optimized operation
      parameters, InflateGRO2 yields optimal lipid packing and reduces lipid vacuum
      exposure to a minimum preserving as much of the equilibrated membrane structure
      as possible. Applicable to atomistic and coarse grain structures in MARTINI
      format, InflateGRO2 offers high accuracy, fast performance, and increased
      application flexibility permitting the easy preparation of systems exhibiting
      heterogeneous lipid composition as well as embedding proteins into multiple
      membranes. Both tools can be used separately, in combination with other methods,
      or in tandem permitting a fully automated workflow while retaining a maximum
      level of usage control and flexibility. To assess the performance of both
      methods, we carried out test runs using 22 membrane proteins of different size
      and transmembrane structure.

PMID- 22989153
TI  - Human NAD(P)H:quinone oxidoreductase type I (hNQO1) activation of quinone
      propionic acid trigger groups.
AB  - NAD(P)H:quinone oxidoreductase type I (NQO1) is a target enzyme for triggered
      delivery of drugs at inflamed tissue and tumor sites, particularly those that
      challenge traditional therapies. Prodrugs, macromolecules, and molecular
      assemblies possessing trigger groups that can be cleaved by environmental stimuli
      are vehicles with the potential to yield active drug only at prescribed sites.
      Furthermore, quinone propionic acids (QPAs) covalently attached to prodrugs or
      liposome surfaces can be removed by application of a reductive trigger stimulus,
      such as that from NQO1; their rates of reductive activation should be tunable via
      QPA structure. We explored in detail the recombinant human NAD(P)H:quinone
      oxidoreductase type I (rhNQO1)-catalyzed NADH reduction of a family of
      substituted QPAs and obtained high precision kinetic parameters. It is found that
      small changes in QPA structure-in particular, single atom and function group
      substitutions on the quinone ring at R(1)-lead to significant impacts on the
      Michaelis constant (K(m)), maximum velocity (V(max)), catalytic constant
      (k(cat)), and catalytic efficiency (k(cat)/K(m)). Molecular docking simulations
      demonstrate that alterations in QPA structure result in large changes in QPA
      alignment and placement with respect to the flavin isoalloxazine ring in the
      active site of rhNQO1; a qualitative relationship exists between the kinetic
      parameters and the depth of QPA penetration into the rhNQO1 active site. From a
      quantitative perspective, a very good correlation is observed between
      log(k(cat)/K(m)) and the molecular-docking-derived distance between the flavin
      hydride donor site and quinone hydride acceptor site in the QPAs, an observation
      that is in agreement with developing theories. The comprehensive kinetic and
      molecular modeling knowledge obtained for the interaction of recombinant human
      NQO1 with the quinone propionic acid analogues provides insight into the design
      and implementation of the QPA trigger groups for drug delivery applications.

PMID- 22989157
TI  - Mutation type and position varies between mosaic and inherited NF2 and correlates
      with disease severity.

PMID- 22989156
TI  - The molecular and enzymatic basis of bitter/non-bitter flavor of citrus fruit:
      evolution of branch-forming rhamnosyltransferases under domestication.
AB  - Domestication and breeding of citrus species/varieties for flavor and other
      characteristics, based on the ancestral species pummelo, mandarin and citron, has
      been an ongoing process for thousands of years. Bitterness, a desirable flavor
      characteristic in the fruit of some citrus species (pummelo and grapefruit) and
      undesirable in others (oranges and mandarins), has been under positive or
      negative selection during the breeding process of new species/varieties.
      Bitterness in citrus fruit is determined by the composition of branched-chain
      flavanone glycosides, the predominant flavonoids in citrus. The flavor
      determining biosynthetic step is catalyzed by two branch-forming
      rhamnosyltransferases that utilize flavanone-7-O-glucose as substrate. The 1,2
      rhamnosytransferase (encoded by Cm1,2RhaT) leads to the bitter flavanone-7-O
      neohesperidosides whereas the 1,6-rhamnosytransferase leads to the
      tastelessflavanone-7-O-rutinosides. Here, we describe the functional
      characterization of Cs1,6RhaT, a 1,6-rhamnosyltransferase-encoding gene directing
      biosynthesis of the tasteless flavanone rutinosides common to the non-bitter
      citrus species. Cs1,6RhaT was found to be a substrate-promiscuous enzyme
      catalyzing branched-chain rhamnosylation of flavonoids glucosylated at positions
      3 or 7. In vivo substrates include flavanones, flavones, flavonols and
      anthocyanins. Cs1,6RhaT enzyme levels were shown to peak in young fruit and
      leaves, and gradually subside during development. Phylogenetic analysis of
      Cm1,2RhaT and Cs1,6RhaT demonstrated that they both belong to the branch-forming
      glycosyltransferase cluster, but are distantly related and probably originated
      separately before speciation of the citrus genome. Genomic data from citrus,
      supported by a study of Cs1,6RhaT protein levels in various citrus species,
      suggest that inheritance, expression levels and mutations of branch-forming
      rhamnosyltransferases underlie the development of bitter or non-bitter
      species/varieties under domestication. 

PMID- 22989155
TI  - A prospective cohort study of health behavior profiles after age 50 and mortality
      risk.
AB  - BACKGROUND: This study examines the mortality risk associated with distinct
      combinations of multiple risk behaviors in middle-aged and older adults, and
      assesses whether the mortality risks of certain health behaviors are moderated by
      the presence of other risk behaviors. METHODS: Data for this prospective cohort
      study are from the Health and Retirement Study (HRS), a nationwide sample of
      adults older than 50 years. Baseline data are from respondents (n = 19,662) to
      the 1998 wave of the HRS. Twelve distinct health behavior profiles were created,
      based on each respondent's smoking, physical activity, and alcohol use status in
      1998. Mortality risk was estimated through 2008 using Cox regression. RESULTS:
      Smoking was associated with elevated risk for mortality within all behavioral
      profiles, but risk was greatest when combined with heavy drinking, both for
      middle-aged (ages 51-65) and older (ages 66+) adults. Profiles that included
      physical inactivity were also associated with increased mortality risk in both
      age groups. However, the impact of inactivity was clearly evident only among non
      smokers; among smokers, the risk of inactivity was less evident, and seemingly
      overshadowed by the risk of smoking. Moderate drinking was protective relative to
      abstinence among non-smokers, and relative to heavy drinking among smokers.
      CONCLUSIONS: In both middle-aged and older adults, multiple unhealthy behaviors
      increase mortality risk. However, the level of risk varies across unique
      combinations of unhealthy behaviors. These findings highlight the role that
      lifestyle improvements could play in promoting healthy aging, and provide insight
      into which behavioral combinations should receive top priority for intervention.

PMID- 22989158
TI  - The role of postoperative positioning after DSAEK in preventing graft
      dislocation.
AB  - PURPOSE: The aim of the study was to evaluate the importance of immediate
      postoperative supine patient positioning after Descemet stripping automated
      endothelial keratoplasty (DSAEK). METHODS: Forty eyes from 40 patients who
      underwent DSAEK were randomized into two groups: 20 patients sat in a chair for 2
      hr postoperatively (group 1), and 20 patients were placed in a supine position
      (group 2) for the same time interval. At the end of surgery, the anterior chamber
      was fully filled with air, aiming at an intraocular pressure (IOP) of
      approximately 20 mmHg. The dislocation rate in the two groups was registered. IOP
      was measured 2 hr postoperatively and compared with endothelial cell loss at 6
      months. RESULTS: There was no statistically significant difference in the
      dislocation rate between the two groups (p = 0.548): two patients (10%) in group
      1 and one patient (5%) in group 2. Endothelial cell loss at 6 months was 29.6%
      and 29.7% in group 1 and 2, respectively. There was no correlation between the
      IOP 2 hr after surgery and endothelial cell loss at 6 months (p = 0.741).
      CONCLUSION: Supine positioning does not seem to be of crucial importance in
      avoiding graft dislocation in DSAEK when the anterior chamber is fully filled
      with air for 2 hr postoperatively.

PMID- 22989160
TI  - Effects of low-level laser therapy (LLLT) and diclofenac (topical and
      intramuscular) as single and combined therapy in experimental model of controlled
      muscle strain in rats.
AB  - Muscle injuries represent ca 30% of sports injuries and excessive stretching of
      muscle causes more than 90% of injuries. Currently the most used treatments are
      nonsteroidal anti-inflammatory drugs (NSAIDs), however, in last years, low-level
      laser therapy (LLLT) is becoming an interesting therapeutic modality. The aim of
      this study was to evaluate the effect of single and combined therapies (LLLT,
      topical application of diclofenac and intramuscular diclofenac) on functional and
      biochemical aspects in an experimental model of controlled muscle strain in rats.
      Muscle strain was induced by overloading tibialis anterior muscle of rats.
      Injured groups received either no treatment, or a single treatment with topical
      or intramuscular diclofenac (TD and ID), or LLLT (3 J, 810 nm, 100 mW) 1 h after
      injury. Walking track analysis was the functional outcome and biochemical
      analyses included mRNA expression of COX-1 and COX-2 and blood levels of
      prostaglandin E2 (PGE2 ). All treatments significantly decreased COX-1 and COX-2
      gene expression compared with injury group (P < 0.05). However, LLLT showed
      better effects than TD and ID regarding PGE2 levels and walking track analysis (P
      < 0.05). We can conclude that LLLT has more efficacy than topical and
      intramuscular diclofenac in treatment of muscle strain injury in acute stage.

PMID- 22989161
TI  - Prognostic indicators in 35 patients with extramammary Paget's disease.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is an uncommon skin tumor that
      usually occurs in the genital area. Few studies on EMPD have been conducted.
      OBJECTIVE: To evaluate the clinical and pathologic features, treatments,
      recurrence, survival rates, and prognostic factors of EMPD. METHODS: A total of
      35 (27 men and 8 women) patients with EMPD was analyzed. The average age of the
      patients was 73.4 years. RESULT: Twenty nine Of the 35 patients had lesions in
      the genital area, one in the genital and perianal area, three in the axillary
      area and two in the perianal area. Eighteen patients had in situ lesions, five
      had inguinal lymph node metastases and two had distant metastases at the time of
      diagnosis. Surgical resection was performed in 30 cases and radiation therapy,
      was administered in three cases. Six patients died of EMPD, and the overall 5
      year survival rate was 75%. CONCLUSION: The presence of a nodule on the primary
      lesion, clinically palpable lymph nodes, the level of tumor invasion, and lymph
      node metastases were found to be significant prognostic factors in the 35 EMPD
      cases at our institution.

PMID- 22989159
TI  - The neuronal insulin sensitizer dicholine succinate reduces stress-induced
      depressive traits and memory deficit: possible role of insulin-like growth factor
      2.
AB  - BACKGROUND: A number of epidemiological studies have established a link between
      insulin resistance and the prevalence of depression. The occurrence of depression
      was found to precede the onset of diabetes and was hypothesized to be associated
      with inherited inter-related insufficiency of the peripheral and central insulin
      receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin
      receptor, was shown to stimulate insulin-dependent H2O2 production of the
      mitochondrial respiratory chain leading to an enhancement of insulin receptor
      autophosphorylation in neurons. As such, this mechanism can be a novel target for
      the elevation of insulin signaling. RESULTS: Administration of DS (25 mg/kg/day,
      intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure,
      diminished manifestations of anhedonia defined in a sucrose test and behavioral
      despair in the forced swim test. Treatment with dicholine succinate reduced the
      anxiety scores of stressed mice in the dark/light box paradigm, precluded stress
      induced decreases of long-term contextual memory in the step-down avoidance test
      and hippocampal gene expression of IGF2. CONCLUSIONS: Our data suggest that
      dicholine succinate has an antidepressant-like effect, which might be mediated
      via the up-regulation of hippocampal expression of IGF2, and implicate the
      neuronal insulin receptor in the pathogenesis of stress-induced depressive
      syndrome.

PMID- 22989162
TI  - Correct equations for calculating the maximum allowable fish consumption rate for
      human health risk assessment considering the noncarcinogenic effects of multiple
      contaminants in fish.

PMID- 22989163
TI  - An analysis of the health service efficiency and patient experience with two
      different intravenous iron preparations in a UK anaemia clinic.
AB  - BACKGROUND: Historically, the Renal Unit at King's College Hospital used
      intravenous (IV) iron sucrose (IS) to treat iron deficiency anaemia in patients
      with chronic kidney disease who were not on dialysis (CKD-ND). As part of a
      service initiative to improve patient experience, new products were considered as
      alternatives. This study investigated the potential impact on patient experience
      and service costs by switching from IS to ferric carboxymaltose (FCM). METHODS: A
      decision analytical model was used to calculate the impact of switching from IS
      to FCM for a cohort of CKD-ND patients. Service provision data were collected for
      365 patients who received 600 mg IS within a 12 month period, creating the IS
      data set. The service provision data, along with a clinically relevant FCM
      administration protocol (stipulating total doses of 500 mg FCM), were used to
      calculate a corresponding theoretical data set for FCM for the same cohort of
      patients. RESULTS: The FCM protocol saved each patient two hospital visits and
      2.66 hours of time (equating to approximately a saving of L36.21 in loss of
      earnings) and L19 in travel costs. Direct attributable costs for iron
      administration (which included drug, disposables, nursing staff, and hospital
      provided patient transport costs) were L58,646 for IS vs L46,473 for FCM. Direct
      overhead costs (which included nursing preparation time, administration staff,
      clinic space, and consultant time costs) were L40,172 for the IS service vs
      L15,174 for the FCM service. LIMITATIONS: Based on clinical experience with the
      products, this analysis assumes that 500 mg FCM is therapeutically equivalent to
      600 mg IS. Consultant time costs are assumed to be the same between the two
      treatment groups. IV iron administration protocols and data are specific to
      King's College Hospital. The design is retrospective and changes to the
      management of the clinic, including service delivery optimization, may also
      affect real costs. CONCLUSION: FCM was associated with fewer hospital visits and
      reduced transport costs for CKD-ND patients receiving IV iron and has the
      potential to save 19-37% in service costs. Owing to increased administration
      efficiency, FCM can improve the overall patient experience while reducing the
      total cost of the King's College Hospital IV iron service for CKD-ND patients,
      compared with treatment with IS.

PMID- 22989164
TI  - A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant
      inbred strains.
AB  - The DBA/2J inbred strain of mice has been used extensively in hearing research as
      it suffers from early-onset, progressive hearing loss. Initially, it mostly
      affects high frequencies, but already at 2-3 months hearing loss becomes broad.
      In search for hearing loss genes other than Cadherin 23 (otocadherin) and fascin
      2, which make a large contribution to the high-frequency deficits, we used a
      large set of the genetic reference population of BXD recombinant inbred strains.
      For frequencies 4, 8, 16 and 32 kHz, auditory brainstem response hearing
      thresholds were longitudinally determined from 2-3 up to 12 weeks of age. Apart
      from a significant, broad quantitative trait locus (QTL) for high-frequency
      hearing loss on chromosome 11 containing the fascin-2 gene, we found a novel,
      small QTL for low-frequency hearing loss on chromosome 18, from hereon called
      ahl9. Real-time quantitative polymerase chain reaction of organs of Corti,
      isolated from a subset of strains, showed that a limited number of genes at the
      QTL were expressed in the organ of Corti. Of those genes, several showed
      significant expression differences based on the parental line contributing to the
      allele. Our results may aid in the future identification of genes involved in low
      frequency, early-onset hearing loss. 

PMID- 22989165
TI  - Influence of non-alcoholic fatty liver disease on the development of diabetes
      mellitus.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is linked to
      metabolic syndrome, and is known to be associated with impaired fasting glycemia
      and diabetes mellitus. This prospective community-based study was conducted to
      determine the association between NAFLD and incidence of diabetes mellitus in an
      urban adult population in Sri Lanka. METHODS: Participants of the Ragama Health
      Study cohort were assessed for NAFLD using established ultrasound criteria in
      2007. Those who were free of diabetes at baseline were followed up for 3 years.
      Incidence rates of diabetes mellitus were compared between subjects with and
      without NAFLD at baseline. RESULTS: Out of 2984 subjects, 926 had NAFLD and 676
      had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007,
      1914 were re-assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD
      and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de
      novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person
      years of follow up for those with and without NAFLD. NAFLD was an independent
      predictor of developing diabetes mellitus. Other independent predictors were
      impaired fasting glycemia and dyslipidemia. CONCLUSIONS: Subjects with
      ultrasonically diagnosed NAFLD have an increased risk of developing diabetes
      mellitus. Intervention for NAFLD through lifestyle modification may prevent
      progression of the current diabetes epidemic.

PMID- 22989166
TI  - Second campaign of microclimate monitoring in the carcer tullianum: temporal and
      spatial correlation and gradients evidenced by multivariate analysis.
AB  - BACKGROUND: This paper discusses results obtained in the second monitoring
      campaign of the Carcer Tullianum, a particular hypogeum environment located in
      the historical centre of Rome (Italy). In the first paper we stressed the need to
      apply chemometric tools to this kind of studies in order to obtain full and
      significant information; really information on sampling design, sensors (type,
      number, position) and instrument validation seems to be not easy to find in
      literature for researches dealing with monitoring of indoor environments.Also in
      this case three main parameters (temperature, humidity, illuminance) were
      monitored in the complex construction by an inexpensive self-assembled system
      along some horizontal and vertical vectors together with some measurements of
      oxygen, carbon dioxide and barometric pressure.With respect to the first
      campaign, we used a higher number of sensors to cover a new excavated zone; for
      the same reason, as well as to take into account the presence of visitors, a
      different experimental design was adopted. RESULTS: Different data treatments
      were applied to data coming from all the used sensors. A good view of the
      microclimate was obtained that also resulted coherent with the different position
      of the three rooms constituting the monitored site (Carcer, Tullianum, Convent).
      Classical time plots resulted useful to evidence the correlation of the main
      monitored parameters (T, RH% and illuminance) with macroclimate, as well as their
      delay in following macroclimate. Box-Whisker and Gain-Loss graphs evidenced at
      the best the microclimate differences between the three rooms; an almost hypogean
      microclimate was evidenced for the lower room (Tullianum) where humidity values
      range between 90 and 100% while lower values, but anyway higher than the
      external, and spread more widely were measured passing to Convent and Carcer with
      minimum values around 50% for the last. A scarce or very scarce correlation with
      macroclimate was evidenced for all the three main measured parameters. Lighting
      results mainly dependent on artificial light and only in few cases, but
      unfortunately in the most precious zone, illuminance exceeds values suggested by
      Normative. CONCLUSIONS: Box-Whisker and Gain-Loss graphs allowed us to have the
      best view of the microclimate for all the monitored rooms. The influence of
      lighting by lamps on the other monitored parameters resulted overlapped and
      clearly topped the solar one. The worst situation was found in the Carcer, where
      the presence of the main chandelier worsens the state of the frescoed walls,
      already subjected to wide changes in temperature and humidity. Also the
      lighthouse located above the Convent provokes lighting exceeding values suggested
      by Normative while, as expected, LEDs resulted as suitable source of light from a
      conservation point of view.Susanne Heidi Plattner, Patrizia Fortini and Maria Pia
      Sammartino contributed equally to this work.

PMID- 22989167
TI  - Association of melanocortin-4 receptor gene polymorphisms with obesity-related
      parameters in Malaysian Malays.
AB  - BACKGROUND: Melanocortin-4 receptor (MC4R) is an important regulator of body
      weight and energy intake. Genetic polymorphisms of the MC4R gene have been found
      to be linked to obesity in many recent studies across the globe. AIM: This study
      aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage
      disequilibrium (LD) pattern and haplotypes in Malaysian Malays. METHODS: The
      study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal
      swabs. Genotyping was performed using Sequenom MassARRAY(r) iPLEX platform.
      Anthropometric and blood lipid profiles were measured. RESULTS: MC4R rs571312 SNP
      was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005),
      while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p =
      0.016). The MC4R rs7227255 SNP did not show any association with obesity
      parameters. CONCLUSIONS: The strength of LD of the MC4R gene region is low and
      the haplotypes were not associated with obesity in Malaysian Malays.

PMID- 22989168
TI  - Abstracts of the 9th Asia Pacific Medical Education Conference (APMEC). National
      University of Singapore, Singapore. January 11-15, 2012.

PMID- 22989170
TI  - An outcomes model to evaluate risks and benefits of Escherichia coli vaccination
      in beef cattle.
AB  - We developed a stochastic simulation model to evaluate the impact of Escherichia
      coli O157:H7 (O157) vaccination on key epidemiological outcomes. The model
      evaluated a reduction in the O157 prevalence in feedlot cattle as well as
      concentration in cattle feces due to vaccination. The impact of this reduction on
      outcomes at slaughter/harvest and consumption was evaluated by simulating the
      relationships between the O157 prevalence and concentration at various points in
      the ground beef supply chain. The uncertainty and variability associated with the
      O157 contamination was explicitly modeled in production, slaughter, and
      consumption modules. Our results show that vaccination can have a significant
      benefit with respect to relevant outcomes such as (1) the number of human O157
      illnesses due to the consumption of ground beef, (2) the number of production
      lots with high O157 contamination levels, (3) the likelihood of detection by U.S.
      Department of Agriculture Food Safety and Inspection Service testing, and (4) the
      probability of multiple illnesses due to ground beef servings from the same lot.
      These results show that these outcomes are strongly impacted by preharvest
      vaccination. For example, if the vaccine is used so as to reduce the prevalence
      of E. coli shedding cattle by 80% and if all U.S. steers and heifers were
      vaccinated, the expected number of human illnesses from ground beef-associated
      O157 would be reduced almost 60%. If the vaccine is 60% or 40% effective, the
      illness rate would be reduced approximately 45% or 40%, respectively. The number
      of production lots (10,000-lb lots) with high O157 contamination levels (> 1000
      servings) would be reduced by 96% if all steers and heifers received an 80%
      effective vaccine regimen. The analysis shows that resulting reduction in the
      number of shedding animals and the reduced concentration of E. coli on carcasses
      can combine to reduce human illnesses and cost to beef packers.

PMID- 22989171
TI  - UV-C inactivation of Cronobacter sakazakii.
AB  - The purpose of this research was to study the effect of different factors on the
      resistance of Cronobacter sakazakii NCTC 9238 to UV-C light (which includes
      germicidal ultraviolet light at 254 nm) and to determine whether a combined
      treatment with heat would produce a synergistic effect for its inactivation.
      Growth temperature between 10 degrees C and 37 degrees C did not change the UV-C
      resistance of C. sakazakii. On the contrary, cells in the logarithmic phase of
      growth were more sensitive to UV-C light than in the stationary phase. The
      lethality of UV-C was independent of pH (between 3.0 and 7.0) and a(w) (between
      0.94 and > 0.99) of the treatment media, but it exponentially decreased with the
      absorption coefficient (alpha). When applying a UV-C treatment of 27.1 J/mL at 25
      degrees C to C. sakazakii suspended in vegetable soup and apple juice, 1 and 2
      log10 cycles of inactivation were barely achieved, respectively. However, the
      bactericidal effect of UV-C light increased with temperature. The lethality of
      the combined process was the result of a synergistic effect that was maximum at
      52.5 degrees C for apple juice and 55 degrees C for vegetable soup. In
      conclusion, these results indicate that UV-C efficacy may be influenced by
      microbial growth conditions and food characteristics, and that its combination
      with heat may act synergistically against C. sakazakii.

PMID- 22989172
TI  - Intestinal atresia occurring in association with placental fetal thrombotic
      vasculopathy: a case report with literature review.
AB  - Fetal thrombotic vasculopathy (FTV) is a thrombo-occlusive disorder of the
      placenta that has been reported in association with perinatal conditions such as
      cardiac abnormalities, neurological injury, and perinatal liver disease. These
      complications are related to fetal circulation vascular compromise. We herein
      report a previously undocumented association of congenital intestinal atresia and
      placental FTV. Vascular occlusion of the fetal mesenteric vessels has been
      hypothesized to result in congenital intestinal atresia. Our report provides
      support for this vascular hypothesis and illustrates the value of formal
      pathological examination of the placenta in explaining this occurrence of
      congenital intestinal atresia.

PMID- 22989173
TI  - Technical competence in surgeons.
AB  - In this paper, we review the literature to date on technical competence in
      surgeons; how it can be defined, taught to trainees and assessed. We also examine
      how we can predict which candidates for surgical training will most likely
      develop technical competence. While technical competency is just one aspect of
      what makes a good surgeon, we have recognized a need to review the literature in
      this area and to combine this with broader definitions of competency. Our review
      found that several methods are available to objectively measure, assess and
      predict technical competence and should be used in surgical training.

PMID- 22989174
TI  - Two-year evaluation of the MiniArc in obese versus non-obese patients for
      treatment of stress urinary incontinence.
AB  - OBJECTIVES: Obesity is a well-established risk factor of stress urinary
      incontinence, which affects up to 35% of adult women worldwide. We evaluated
      whether there is a difference in outcomes with MiniArc sling for treatment of
      stress incontinence in obese women versus non-obese women at 24 months. METHODS:
      A 2-year subanalysis of obese (body mass index >30 kg/m(2) ) versus non-obese
      patients enrolled into a multicenter, prospective study evaluating the
      effectiveness of MiniArc sling was carried out. Qualitative (Urogenital Distress
      Inventory 6 and Incontinence Impact Questionnaire 7) and quantitative
      measurements, including the cough stress test, were carried out. Secondary
      outcome measures included procedure time, estimated blood loss, length of stay,
      perioperative complications, Wong-Baker Faces Pain Scale and adverse events.
      RESULTS: Of 188 patients, 62 were obese. The mean procedure time, blood loss and
      length of stay were no different between groups. Obese patients reported
      significantly more pain immediately postoperatively (2 vs 1, Wong-Baker, P =
      0.042), but there was no difference at postoperative day 7. There was no
      difference in objective cure using the cough stress test (81% obese vs 86% non
      obese; P = 0.449). Urogenital Distress Inventory 6 and Incontinence Impact
      Questionnaire 7 median scores showed no difference between groups in improvement
      (P = 0.126 and P = 0.087, respectively). No serious device-related complications
      were reported in either group. CONCLUSIONS: The MiniArc sling represents a safe
      and effective treatment option for both obese and non-obese patients with stress
      incontinence. Comparable outcomes at 2 years can be obtained in terms of cure
      rates using the cough stress test or questionnaires, as well as complication
      rates.

PMID- 22989175
TI  - The importance of interaction in the implementation of information technology in
      health care: a symbolic interactionism study on the meaning of accessibility.
AB  - A challenge when groups from different disciplines work together in implementing
      health information technology (HIT) in a health-care context is that words often
      have different meanings depending upon work practices, and definition of
      situations. Accessibility is a word commonly associated with HIT implementation.
      This study aimed to investigate different meanings of accessibility when
      implementing HIT in everyday work practice in a health-care context. It focused
      on the perspective of nurses to highlight another view of the complex
      relationship between HIT and information in a health-care context. This is a
      qualitative study influenced by institutional ethnographic. District nurses and
      student nurses were interviewed. The results indicate that when implementing HIT
      accessibility depends on working routines, social structures and patient
      relationship. The findings of the study suggest that interaction needs to take on
      a more important role when implementing HIT because people act upon words from
      the interpreted meaning of them. Symbolic interactionism is proposed as a way to
      set a mutual stage to facilitate an overall understanding of the importance of
      the meaning of words. There is a need for making place and space for negotiation
      of the meaning of words when implementing HIT in everyday work practice.

PMID- 22989176
TI  - Does parkland influence walking? The relationship between area of parkland and
      walking trips in Melbourne, Australia.
AB  - BACKGROUND: Using two different measures of park area, at three buffer distances,
      we sought to investigate the ways in which park area and proximity to parks, are
      related to the frequency of walking (for all purposes) in Australian adults.
      Little previous research has been conducted in this area, and results of existing
      research have been mixed. METHODS: Residents of 50 urban areas in metropolitan
      Melbourne, Australia completed a physical activity survey (n = 2305). Respondents
      reported how often they walked for >=10 minutes in the previous month. Walking
      frequency was dichotomised to 'less than weekly' (less than 1/week) and 'at least
      weekly' (1/week or more). Using Geographic Information Systems, Euclidean buffers
      were created around each respondent's home at three distances: 400metres (m), 800
      m and 1200 m. Total area of parkland in each person's buffer was calculated for
      the three buffers. Additionally, total area of 'larger parks', (park space >=
      park with Australian Rules Football oval (17,862 m2)), was calculated for each
      set of buffers. Area of park was categorised into tertiles for area of all parks,
      and area of larger parks (the lowest tertile was used as the reference category).
      Multilevel logistic regression, with individuals nested within areas, was used to
      estimate the effect of area of parkland on walking frequency. RESULTS: No
      statistically significant associations were found between walking frequency and
      park area (total and large parks) within 400 m of respondent's homes. For total
      park area within 800 m, the odds of walking at least weekly were lower for those
      in the mid (OR 0.65, 95% CI 0.46-0.91) and highest (OR 0.65, 95% CI 0.44-0.95)
      tertile of park area compared to those living in areas with the least amount of
      park area. Similar results were observed for total park area in the 1200 m
      buffers. When only larger parks were investigated, again more frequent walking
      was less likely when respondents had access to a greater amount of park area.
      CONCLUSIONS: In this study we found that more park area in residential
      environments reduced the odds of walking more frequently. Other area
      characteristics such as street connectivity and destinations may underlie these
      associations by negatively correlating with park area.

PMID- 22989177
TI  - Fatal transorbital penetrating intracranial injury caused by a bicycle hand
      brake.
AB  - A transorbital penetrating intracranial injury is a rare and severe traumatic
      brain injury. Patients with this type of injury may present dramatically, but
      often the injury is subtle and therefore easily overlooked and not recognized in
      the first place. We present the case of a 45-year-old female admitted to the
      emergency department after she fell with her bike and the bicycle brake handle
      penetrated her left eye. A computerized tomography of the cerebrum showed a
      fracture of the superior orbital roof with multiple bone fragments extending into
      the brain near the circle of Willis. A pneumocephalus and traumatic frontobasal,
      intraventricular and subdural hemorrhage was seen. The patient deteriorated
      suddenly and was transferred to a neurosurgical center where she underwent an
      emergency craniotomy with evacuation of the intracerebral hematoma and an
      intraventricular drain was placed. After surgery, the patient's condition
      deteriorated, and total compression of the brain stem occurred, upon which the
      patient was declared brain dead. Our case report shows that the Glasgow Coma
      Scale score at admission is not always a good predictor of the severity of the
      injury. Even when there is minimal suspicion of a penetrating intracranial
      injury, a computerized tomography should be performed immediately, independent of
      the patient's Glasgow Coma Scale score. A direct transfer to a specialized
      neurosurgical center is recommended because this injury often results in death
      due to fatal complications such as intracerebral hemorrhage, pneumocephalus and
      brain stem injury.

PMID- 22989178
TI  - Solvent effect in reactions using Stryker's reagent.
AB  - The solvent has a significant influence in the rate of reactions promoted by
      Stryker's reagent. The reactions performed in THF were, in most cases, faster
      than in toluene.

PMID- 22989179
TI  - Populated intermediates in the thermal unfolding of the human telomeric
      quadruplex.
AB  - Thermal denaturation profiles of several model oligonucleotides of the human
      telomere DNA sequence including d[A(GGGTTA)(3)GGG] (Tel22) were determined using
      circular dichroism (CD), fluorescence of adenine -> 2-aminopurine analogs, and
      fluorescence resonance energy transfer (FRET) to monitor the unfolding process at
      specific locations within the quadruplex. The resulting optical spectra vs
      temperature data matrices were analyzed by singular value decomposition (SVD) to
      ascertain the minimum number of species required to reproduce the unfolding
      spectral profiles. Global nonlinear least-squares fitting of the SVD amplitude
      vectors was used to estimate thermodynamic parameters and optical spectra of all
      species for a series of unfolding mechanisms that included one-, two-, and three
      step sequential pathways F ? I(n) ? U, n = 0, 1, or 2) as well as two mechanisms
      with spectroscopically distinct starting structures (F(1) and F(2)). The CD and
      FRET data for Tel22 unfolding between 4 and 94  degrees C in 25 mM KCl were best
      described by a sequential unfolding model with two intermediates, while the 2
      aminopurine analogs required one intermediate. The higher melting intermediate
      I(2) had a transition midpoint temperature (T(m)) of 61  degrees C and a CD
      spectrum with a maximum and minimum at ~265 and ~245 nm, respectively. The
      fluorescence emission spectra of the 2-aminopurine and FRET derivatives suggest
      greater solvent exposure of the 5'-AGGGTTA- segment in the intermediate compared
      to the folded state. The spectroscopic properties of the 61  degrees C
      intermediate suggest that it may be a triple helical structure.

PMID- 22989180
TI  - Results of clot waveform analysis and thrombin generation test for a plasma
      derived factor VIIa and X mixture (MC710) in haemophilia patients with inhibitors
      -phase I trial: 2nd report.
AB  - We reported the results of a clinical pharmacological study of MC710 (a mixture
      of plasma-derived FVIIa and FX) in haemophilia patients with inhibitors during a
      non-haemorrhagic state. This report provides the results of a clot waveform
      analysis (CWA) and thrombin generation test (TGT) using blood samples obtained in
      this study. CWA and TGT were conducted using blood samples obtained from a
      pharmacokinetic and pharmacodynamic study in which MC710 (five dose rates: 20,
      40, 80, 100 and 120 MUg kg(-1)) was compared with NovoSeven (120 MUg kg(-1)) and
      FEIBA (two dose rates: 50 and 75 U kg(-1)) as control drugs in 11 haemophilia
      patients with inhibitors without haemorrhagic symptoms. CWA showed that MC710
      provided significantly greater improvement than the control drugs in activated
      partial thromboplastin time (APTT) at 80 MUg kg(-1); maximum clot velocity and
      maximum clot acceleration were more enhanced by MC710 than by control drugs. TGT
      revealed that MC710 significantly shortened the initiation time of thrombin
      generation in comparison to FEIBA and induced greater thrombin generation potency
      than NovoSeven. It was not clear whether or not MC710 caused significant dose
      dependent changes in the two measurements; however, differences between MC710 and
      the control drugs were clarified. MC710 was confirmed to have superior
      coagulation activity and thrombin productivity and is expected to have superior
      bypassing activity.

PMID- 22989181
TI  - Metal-ion dependent catalytic properties of Sulfolobus solfataricus class ii
      alpha-mannosidase.
AB  - The active site for the family GH38 class II alpha-mannosidase is constituted in
      part by a divalent metal ion, mostly Zn(2+), as revealed in the crystal
      structures of enzymes from both animal and bacterial sources. The metal ion
      coordinates to the bound substrate and side chains of conserved amino acid
      residues. Recently, evidence has accumulated that class II alpha-mannosidase is
      active in complex with a range of divalent metal ions. In the present work, with
      employment of the class II alpha-mannosidase, ManA, from the hyperthermophilic
      archaeon Sulfolobus solfataricus, we explored the influence of the divalent metal
      ion on the associated steady-state kinetic parameters, K(M) and k(cat), for
      various substrates. With p-nitrophenyl-alpha-d-mannoside as a substrate, the
      enzyme showed activity in the presence of Co(2+), Cd(2+), Mn(2+), and Zn(2+),
      whereas Ni(2+) and Cu(2+) were inhibitory and nonactivating. Co(2+) was the
      preferred metal ion, with a k(cat)/K(M) value of about 120 mM(-1) s(-1), 6 times
      higher than that with Cd(2+) and Zn(2+) and 10 times higher than that with
      Mn(2+). With alpha-1,2-, alpha-1,3-, alpha-1,4-, or alpha-1,6-mannobiose as a
      substrate, Co(2+) was the only metal ion promoting hydrolysis of all substrates;
      however, Mn(2+), Cd(2+), and Zn(2+) could substitute to a varying extent. A
      change in the divalent metal ion generally affected the K(M) for the hydrolysis
      of p-nitrophenyl-alpha-d-mannoside; however, changes in both k(cat) and K(M) for
      the hydrolysis of alpha-mannobioses were observed, along with changing
      preferences for the glycosidic linkage. Finally, it was found that the metal ion
      and substrate bind in that order via a steady-state, ordered, sequential
      mechanism.

PMID- 22989183
TI  - Seroepidemiology of Coxiella burnetii in wild white-tailed deer (Odocoileus
      virginianus) in New York, United States.
AB  - Coxiella burnetii is an environmentally resistant bacterium that has been
      reported in wildlife populations. Frequent contact on pasture between white
      tailed deer (Odocoileus virginianus) and cattle has been reported by farmers in
      the Northeast U.S., and transmission of C. burnetii is thought to occur between
      wild deer and domestic livestock such as cows, sheep, and goats. Blood samples
      were collected from white-tailed deer throughout New York State in 2009 and 2010
      and examined for anti-C. burnetii phase II antibodies via indirect
      microimmunofluorescence assays. Exploratory spatial cluster analysis revealed a
      lack of significant clustering of C. burnetii-seropositive deer. Logistic
      regression analysis revealed a significant association between the C. burnetii
      serostatus of deer and sex, percent agriculture, shrub, and forest cover, and
      townships with more than 10 bovine herds. A lack of significant association was
      revealed between the serostatus of deer and the year of sampling, soil type,
      percent wetland and open water cover, total annual precipitation, and townships
      with more than two sheep or goat herds. Because four different land cover types
      were associated with a higher probability of C. burnetii seropositivity, it is
      likely that land cover is not a discriminating factor in C. burnetii exposure.
      This is probably because C. burnetii environmental contamination is widespread
      and not localized to certain cover types. The social behavior of male deer may
      contribute to the lack of spatial clustering. Bucks typically travel over greater
      distances, which leads to a greater variety of encountered environments and a
      greater chance for exposure to C. burnetii. Because increasing agricultural land
      cover and townships with greater than 10 bovine herds are associated with an
      increased probability of diagnosing a seropositive deer, it appears likely that
      transmission of C. burnetii between domestic livestock and white-tailed deer may
      occur.

PMID- 22989182
TI  - Serological evidence of flaviviruses and alphaviruses in livestock and wildlife
      in Trinidad.
AB  - Seroprevalence rates of selected arboviruses in animal populations in Trinidad
      were determined using serum samples collected between 2006 and 2009 from horses
      (n=506), cattle (n=163), sheep (n=198), goats (n=82), pigs (n=184), birds
      (n=140), rodents (n=116), and other vertebrates (n=23). The sera were screened
      for antibodies to West Nile virus (WNV), St. Louis encephalitis virus (SLEV),
      Ilheus virus (ILHV), Bussuquara virus (BSQV), Venezuelan equine encephalitis
      virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine
      encephalitis virus (WEEV), using hemagglutination inhibition assay (HIA) and
      epitope-blocking enzyme-linked immunosorbent assays (ELISA). Antibodies to SLEV
      were detected in a total of 49 (9.7%) horses, 8 (4.9%) cattle, 1 (1.2%) goat, 2
      (1.4%) wild birds, and 3 (2.2%) wild rodents by both methods. In contrast,
      antibodies to EEEV, VEEV, and WNV were detected only in horses, at rates of 4.3%,
      0.8%, and 17.2%, respectively, by ELISA, and IgM capture ELISA was WNV-positive
      in 3 (0.6%) of these sera. Among locally bred unvaccinated horses that had never
      left Trinidad, seroprevalence rates against WNV were 12.1% and 17.2% by ELISA and
      HIA, respectively. The presence of WNV- and SLEV-specific antibodies in a
      representative sample of horse sera that were both ELISA- and HIA-seropositive
      was confirmed by plaque reduction neutralization testing (PRNT). Antibodies to
      ILHV and BSQV were not detected in any of the serum samples tested (i.e., sera
      from horses, other livestock, and wild birds in the case of ILHV, and wild
      mammals in the case of BSQV). The data indicate the presence of WNV in Trinidad,
      and continuing low-level circulation of SLEV, EEEV, and VEEV.

PMID- 22989185
TI  - Modeling of open, closed, and open-inactivated states of the hERG1 channel:
      structural mechanisms of the state-dependent drug binding.
AB  - The human ether-a-go-go related gene 1 (hERG1) K ion channel is a key element for
      the rapid component of the delayed rectified potassium current in cardiac
      myocytes. Since there are no crystal structures for hERG channels, creation and
      validation of its reliable atomistic models have been key targets in molecular
      cardiology for the past decade. In this study, we developed and vigorously
      validated models for open, closed, and open-inactivated states of hERG1 using a
      multistep protocol. The conserved elements were derived using multiple-template
      homology modeling utilizing available structures for Kv1.2, Kv1.2/2.1 chimera,
      and KcsA channels. Then missing elements were modeled with the ROSETTA De Novo
      protein-designing suite and further refined with all-atom molecular dynamics
      simulations. The final ensemble of models was evaluated for consistency to the
      reported experimental data from biochemical, biophysical, and
      electrophysiological studies. The closed state models were cross-validated
      against available experimental data on toxin footprinting with protein-protein
      docking using hERG state-selective toxin BeKm-1. Poisson-Boltzmann calculations
      were performed to determine gating charge and compare it to electrophysiological
      measurements. The validated structures offered us a unique chance to assess
      molecular mechanisms of state-dependent drug binding in three different states of
      the channel.

PMID- 22989184
TI  - Absence of deficits in social behaviors and ultrasonic vocalizations in later
      generations of mice lacking neuroligin4.
AB  - Mutations in NLGN4X have been identified in individuals with autism spectrum
      disorders and other neurodevelopmental disorders. A previous study reported that
      adult male mice lacking neuroligin4 (Nlgn4) displayed social approach deficits in
      the three-chambered test, altered aggressive behaviors and reduced ultrasonic
      vocalizations. To replicate and extend these findings, independent comprehensive
      analyses of autism-relevant behavioral phenotypes were conducted in later
      generations of the same line of Nlgn4 mutant mice at the National Institute of
      Mental Health in Bethesda, MD, USA and at the Institut Pasteur in Paris, France.
      Adult social approach was normal in all three genotypes of Nlgn4 mice tested at
      both sites. Reciprocal social interactions in juveniles were similarly normal
      across genotypes. No genotype differences were detected in ultrasonic
      vocalizations in pups separated from the nest or in adults during reciprocal
      social interactions. Anxiety-like behaviors, self-grooming, rotarod and open
      field exploration did not differ across genotypes, and measures of developmental
      milestones and general health were normal. Our findings indicate an absence of
      autism-relevant behavioral phenotypes in subsequent generations of Nlgn4 mice
      tested at two locations. Testing environment and methods differed from the
      original study in some aspects, although the presence of normal sociability was
      seen in all genotypes when methods taken from Jamain et al. (2008) were used. The
      divergent results obtained from this study indicate that phenotypes may not be
      replicable across breeding generations, and highlight the significant roles of
      environmental, generational and/or procedural factors on behavioral phenotypes. 

PMID- 22989186
TI  - Investigation of primary microcephaly in Bushehr province of Iran: novel STIL and
      ASPM mutations.

PMID- 22989187
TI  - The effect of being overweight on survival in patients with gastric cancer
      undergoing adjuvant chemoradiotherapy.
AB  - The aim of this study was to examine the effect of being overweight on survival
      in patients with gastric cancer undergoing adjuvant chemoradiotherapy and
      chemotherapy. In this study 152 patients were evaluated. Radiotherapy dose was 45
      Gy given in 5 weeks. 5-FU 425 mg/m(2) and folinic acid 20 mg/m(2) were
      administered weekly during the radiotherapy and four cycles with 4-week intervals
      as consolidation chemotherapy after radiotherapy. Patients were assigned into two
      groups according to their body mass index: overweight (body mass index >=25
      kg/m(2)) and normal weight (body mass index <25.0 kg/m(2)). The median overall
      survival was 39 months vs. 18 months and median disease-free survival was 27
      months vs. 13 months in the overweight and normal-weight groups respectively (P =
      0.004 and P = 0.006 respectively). The 5-year survival was better in the patients
      with overweight than those with normal weight (42% vs. 17%; P = 0.004). The
      overall survival was significantly better with being overweight and early
      pathological stage (P = 0.016 and P = 0001 respectively). Overall survival,
      disease-free survival and long-term survival in patients with gastric cancer
      undergoing adjuvant treatment were better in overweight than normal-weight
      patients. Moreover, it was shown that body mass index and pathological stage were
      associated to survival and prognosis.

PMID- 22989188
TI  - Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia
      through activation of canonical Notch pathway.
AB  - BACKGROUND: Electroacupuncture (EA) pretreatment can induce the tolerance against
      focal cerebral ischemia. However, the underlying mechanisms have not been fully
      understood. Emerging evidences suggest that canonical Notch signaling may be
      involved in ischemic brain injury. In the present study, we tested the hypothesis
      that EA pretreatment-induced tolerance against focal cerebral ischemia is
      mediated by Notch signaling. RESULTS: EA pretreatment significantly enhanced
      Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1
      intracellular domain level, which could be increased evidently by ischemia. After
      ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in
      ischemic striatum in EA pretreatment group were increased and reached the peak at
      2 h and 24 h, respectively, which were both earlier than the peak achieved in
      control group. Intraventricular injection with the gamma-secretase inhibitor
      MW167 attenuated the neuroprotective effect of EA pretreatment. CONCLUSIONS: EA
      pretreatment induces the tolerance against focal cerebral ischemia through
      activation of canonical Notch pathway.

PMID- 22989189
TI  - An evaluation of the appropriateness and safety of nurse and midwife prescribing
      in Ireland.
AB  - AIM: To evaluate the clinical appropriateness and safety of nurse and midwife
      prescribing practice. BACKGROUND: The number of countries introducing nurse and
      midwife prescribing is increasing; however, concerns over patient safety remain.
      DESIGN: A multi-site documentation evaluation was conducted using purposeful and
      random sampling. The sample included 142 patients' records and 208 medications
      prescribed by 25 Registered Nurse Prescribers. METHODS: Data were extracted from
      patient and prescription records between March-May 2009. Two expert reviewers
      applied the modified Medication Appropriate Index tool (8 criteria) to each drug.
      The percentage of appropriate or inappropriate responses for each criterion was
      reported. Reviewer concordance was measured using the Cohen's kappa statistic
      (inter-rater reliability). RESULTS: Nurse or midwife prescribers from eight
      hospitals working in seventeen different areas of practice were included. The
      reviewers judged that 95-96% of medicines prescribed were indicated and effective
      for the diagnosed condition. Criteria relating to dosage, directions, drug-drugs
      or disease-condition interaction, and duplication of therapy were judged
      appropriate in 87-92% of prescriptions. Duration of therapy received the lowest
      value at 76%. Overall, reviewers indicated that between 69 (reviewer 2)-80%
      (reviewer 1) of prescribing decisions met all eight criteria. CONCLUSION: The
      majority of nurse and midwife prescribing decisions were deemed safe and
      clinically appropriate. However, risk of inappropriate prescribing with the
      potential for drug errors was detected. Continuing education and evaluation of
      prescribing practice, especially related to drug and condition interactions, is
      required to maximize appropriate and safe prescribing.

PMID- 22989191
TI  - Effect of a novel fixation method for spinal cord stimulators.
AB  - INTRODUCTION: Spinal cord stimulation is a well-established treatment for
      recalcitrant pain syndromes such as failed back surgery syndrome. Techniques
      minimizing surgical time and incision size and increasing lead stability are of
      great value to both the patient and implanting physician. We present a
      consecutive case series review of ten permanent percutaneous spinal cord implants
      utilizing a novel lead fixation device. The purpose of this case series review is
      to present initial findings of the minimized incision size and thoughts
      surrounding the new device and technique. CASE SERIES REPORT: Ten cases were
      performed utilizing the new device (fiXate) and technique. Incision size was
      dictated by adequate visualization of the fascial stratum as well as technical
      working space required for lead fixation and redirection to the generator pocket.
      Each spinal cord stimulator lead was affixed to the thoracodorsal fascia
      utilizing the novel device. DISCUSSION: In this consecutive series, the average
      midline incision size was 2.2 cm (range = 1.9-2.6 cm) which is greatly minimized
      through the use of the device. Not only may fiXate directly affect incision size,
      operating room and anesthesia time may also be lessened due to the semiautomated
      nature of the device. Of the cases performed, there were no complications or
      adverse events. Of note, there have been no reports of lead migrations during
      this case series, the average follow-up time being 18 weeks (range 11-26 weeks).
      CONCLUSION: These data suggest a new method of fixation can be utilized for
      percutaneous spinal cord stimulation that allows a reduction in incision size.
      Intuitively, reduction in incision size is relevant with regard to tissue
      morbidity and may also have implications with regard to infection. Use of the
      device may also reduce operating room and anesthesia time as well as provide
      greater stability than standard suture.

PMID- 22989190
TI  - Attenuation of hepatic fibrosis by an imidazolium salt in thioacetamide-induced
      mouse model.
AB  - BACKGROUND AND AIM: Hepatic fibrosis is a worldwide healthy burden associated
      with significant morbidity and mortality. It is caused by a variety of chronic
      liver injuries. There is currently no effective treatment for liver fibrosis. In
      this report, we tested an imidazolium salt, 1,3-diisopropylimidazolium
      tetrafluoroborate (DPIM), for its anti-fibrotic properties in the thioacetamide
      induced mouse model. METHODS: DPIM was orally delivered to the thioacetamide
      treated mice via drinking water for 12 weeks at the onset of thioacetamide
      treatment at a concentration of 0.1% (prevention group), and for 4 weeks starting
      at the 8(th)  week at a concentration of 0.1% or 0.2% (attenuation group),
      respectively. Messenger RNA and protein were determined by real-time polymerase
      chain reaction and Western blotting, matrix metalloproteinase (MMP) activities
      were measured by fluorogenic peptide substrate and zymography. Mitogen-activated
      protein kinase (MAPK) and PI3K inhibitors were applied in HSC-T6 cells in
      combination of DPIM to probe possible signal pathways underlying the compound's
      action. RESULTS: We observed a significant reduction in collagen deposition in
      both prevention and attenuation groups. The alpha-smooth muscle actin (SMA) and
      transforming growth factor (TGF)-beta gene expressions were also reduced in both
      groups. The reduction of collagen deposition could be in part attributed to the
      suppression of CCR-2 expression and the enhanced matrix protein remodeling by
      metalloproteinases, especially MMP-3. MAPK and PI3K signaling pathways may be
      partially participated in DPIM's molecular action. CONCLUSION: DPIM reduced
      fibrosis in the thioacetamide-induced mouse liver fibrosis model, and warranted
      further studies for possible clinical application in the future.

PMID- 22989192
TI  - Neuroimaging characteristics and growth pattern on magnetic resonance imaging in
      a 52-year-old man presenting with pituicytoma: a case report.
AB  - INTRODUCTION: Pituicytoma is a rare neoplasm of the neurohypophysis. To the best
      of our knowledge there have been no reports of pituicytoma in which long-term
      magnetic resonance imaging observation was performed. We calculated the doubling
      time of the tumor volume and described the growth pattern of a pituicytoma. CASE
      PRESENTATION: A 52-year-old Japanese man with a history of decreased libido was
      found to have a sellar and suprasellar mass. He underwent transsphenoidal
      surgery, but only a small specimen was obtained because of intraoperative
      bleeding. The tentative histological diagnosis was schwannoma. He noticed
      bitemporal hemianopsia 7 years later. A follow-up magnetic resonance imaging
      disclosed a tumor volume doubling time of 3830 days. Transcranial gross-total
      tumor resection was performed. The lesion consisted of elongated and plump tumor
      cells that were arranged in a fascicular or storiform pattern and were positive
      for S-100 protein and focally positive for glial fibrillary acidic protein. The
      final histological diagnosis was pituicytoma. CONCLUSION: Pituicytoma is a slow
      growing tumor, but the growth rate may change during follow-up.

PMID- 22989193
TI  - Second trimester maternal serum markers and a predictive model for predicting
      fetal hemoglobin Bart's disease.
AB  - OBJECTIVE: To compare the levels of maternal serum alpha-fetoprotein (AFP),
      unconjugated estriol (uE3) and free beta-human chorionic gonadotropin (free beta
      hCG) between pregnancies with fetal Hb Bart's disease and unaffected pregnancies.
      METHODS: 148 pregnancies at risk of fetal Hb Bart's disease scheduled for
      cordocentesis at 18 to 22 weeks were prospectively recruited into the study. AFP,
      uE3 and free beta-hCG concentrations were measured before cordocentesis and the
      final fetal diagnosis of Hb Bart's disease was based on fetal Hb typing using
      high-performance liquid chromatography. RESULTS: AFP and free beta-hCG were
      significantly higher whereas uE3 was lower in women with fetal Hb Bart's disease
      than those with unaffected fetuses (1.94 MoM, 1.38 MoM and 0.81 MoM
      respectively). Hb Bart's predictive model; probability = 1/1+e(-[2.876 +
      1.333(AFP) - 6.310(uE3)]), effectively predicted fetal Hb Bart's disease (AUC ROC
      0.91, 95% CI 0.84-0.97) with 61.5% sensitivity and 98.1% specificity using a cut
      off probability at greater than 0.5. CONCLUSIONS: In triple test, serum AFP and
      hCG levels are significantly higher while serum uE3 is significantly lower in
      pregnancies with fetal Hb Bart's disease. Hb Bart's predictive model included AFP
      and uE3 is relatively effective and may be helpful in Hb Bart's prenatal
      screening.

PMID- 22989194
TI  - Flexibility of event boundaries in autobiographical memory.
AB  - Events have clear and consistent boundaries that are defined during perception in
      a manner that influences memory performance. The natural process of event
      segmentation shapes event definitions during perception, and appears to play a
      critical role in defining distinct episodic memories at encoding. However, the
      role of retrieval processes in modifying event definitions is not clear. We
      explored how such processes changed event boundary definitions at recall. In
      Experiment 1 we showed that distance from encoding is related to boundary
      flexibility. Participants were more likely to move self-reported event boundaries
      to include information reported beyond those boundaries when recalling more
      distant events compared to more recent events. In Experiment 2 we showed that age
      also influenced boundary flexibility. Older Age adults were more likely to move
      event boundaries than College Age adults, and the relationship between distance
      from encoding and boundary flexibility seen in Experiment 1 was present only in
      College Age and Middle Age adults. These results suggest that factors at
      retrieval have a direct impact on event definitions in memory and that, although
      episodic memories may be initially defined at encoding, these definitions are not
      necessarily maintained in long-term memory.

PMID- 22989195
TI  - Fluconazole resistance in cryptococcal disease: emerging or intrinsic?
AB  - With the widespread use of long-term fluconazole prophylaxis and suppressive
      treatment, the potential development of fluconazole resistance poses a threat to
      the management of cryptococcal disease. Interpretive breakpoints for the in vitro
      antifungal susceptibility testing of C. neoformans have not been established and
      it is unclear whether the fluconazole minimum inhibitory concentration (MIC) is
      clinically relevant. To gain insight into the management of patients with
      cryptococcosis who fail fluconazole therapy, we conducted a PubMed literature
      search for cases of fluconazole-resistant cryptococcosis reported from 1991 to
      2011. A total of 20 such cases were identified in which most patients had AIDS
      and 30% had never had prior exposure to fluconazole. Fluconazole failure in
      patients with cryptococcal disease cannot be fully attributed to emerging
      resistance of the etiologic agent and heteroresistance is a potential alternative
      mechanism. There is a need to refine the definition of fluconazole-resistant
      cryptococcosis and additional studies of such patients will improve treatment
      strategies and outcomes.

PMID- 22989196
TI  - Emergence of pathogenicity in the Sporothrix schenckii complex.
AB  - Sporothrix schenckii sensu lato is a complex of thermally dimorphic species whose
      natural habitats are soil and plant materials. However, the traumatic
      implantation of the species into human skin is traditionally thought to be the
      route leading to the fungal disease sporotrichosis. The complex contains
      Sporotrhix mexicana, S. globosa, S. brasiliensis, S. luriei, in addition to S.
      schenckii sensu stricto. In this study we evaluated the differences among these
      species relative to their frequency in the environment and in human hosts, as
      well as discuss their remarkable diverse pathogenicity. Today, S. brasiliensis is
      epidemic in and geographically restricted to Brazil. In contrast, S. mexicana and
      S. globosa have rarely been reported over the decades. We discovered that the
      species have been present in collections from clinical cases since 1955 and were
      able to re-identify six isolates originally classified as S. schenckii as
      Sporothrix mexicana (three isolates) and Sporothrix globosa (three isolates).
      Despite their long presence as potential human pathogens they have not shown any
      increase in frequency as etiologic agents of human infections.

PMID- 22989197
TI  - A new modular approach to nanoassembly: stable and addressable DNA nanoconstructs
      via orthogonal click chemistries.
AB  - Thermodynamic instability is a problem when assembling and purifying complex DNA
      nanostructures formed by hybridization alone. To address this issue, we have used
      photochemical fixation and orthogonal copper-free, ring-strain-promoted, click
      chemistry for the synthesis of dimeric, trimeric, and oligomeric modular DNA
      scaffolds from cyclic, double-stranded, 80-mer DNA nanoconstructs. This
      particular combination of orthogonal click reactions was more effective for
      nanoassembly than others explored. The complex nanostructures are stable to heat
      and denaturation agents and can therefore be purified and characterized. They are
      addressable in a sequence-specific manner by triplex formation, and they can be
      reversibly and selectively deconstructed. Nanostructures utilizing this
      orthogonal, chemical fixation methodology can be used as building blocks for
      nanomachines and functional DNA nanoarchitectures.

PMID- 22989198
TI  - Effects of light-emitting diode radiations on human retinal pigment epithelial
      cells in vitro.
AB  - Human visual system is exposed to high levels of natural and artificial lights of
      different spectra and intensities along lifetime. Light-emitting diodes (LEDs)
      are the basic lighting components in screens of PCs, phones and TV sets; hence it
      is so important to know the implications of LED radiations on the human visual
      system. The aim of this study was to investigate the effect of LEDs radiations on
      human retinal pigment epithelial cells (HRPEpiC). They were exposed to three
      light-darkness (12 h/12 h) cycles, using blue-468 nm, green-525 nm, red-616 nm
      and white light. Cellular viability of HRPEpiC was evaluated by labeling all
      nuclei with DAPI; Production of reactive oxygen species (ROS) was determined by
      H2DCFDA staining; mitochondrial membrane potential was quantified by TMRM
      staining; DNA damage was determined by H2AX histone activation, and apoptosis was
      evaluated by caspases-3,-7 activation. It is shown that LED radiations decrease
      75-99% cellular viability, and increase 66-89% cellular apoptosis. They also
      increase ROS production and DNA damage. Fluorescence intensity of apoptosis was
      3.7% in nonirradiated cells and 88.8%, 86.1%, 83.9% and 65.5% in cells exposed to
      white, blue, green or red light, respectively. This study indicates three light
      darkness (12 h/12 h) cycles of exposure to LED lighting affect in vitro HRPEpiC.

PMID- 22989199
TI  - Recovery of retinal pigment epithelium correlating with restoration of retinal
      sensitivity in eyes with a retinal pigment epithelial tear.

PMID- 22989200
TI  - The less healthy urban population: income-related health inequality in China.
AB  - BACKGROUND: Health inequality has been recognized as a problem all over the
      world. In China, the poor usually have less access to healthcare than the better
      off, despite having higher levels of need. Since the proportion of the Chinese
      population living in urban areas increased tremendously with the urbanization
      movements, attention has been paid to the association between urban/rural
      residence and population health. It is important to understand the variation in
      health across income groups, and in particular to take into account the effects
      of urban/rural residence on the degree of income-related health inequalities.
      METHODS: This paper empirically assesses the magnitude of rural/urban disparities
      in income-related adult health status, i.e., self-assessed health (SAH) and
      physical activity limitation, using Concentration Indices. It then uses
      decomposition methods to unravel the causes of inequalities and their variations
      across urban and rural populations. Data from the China Health and Nutrition
      Survey (CHNS) 2006 are used. RESULTS: The study finds that the poor are less
      likely to report their health status as "excellent or good" and are more likely
      to have physical activity limitation. Such inequality is more pronounced for the
      urban population than for the rural population. Results from the decomposition
      analysis suggest that, for the urban population, 76.47 per cent to 79.07 per cent
      of inequalities are driven by non-demographic/socioeconomic-related factors,
      among which income, job status and educational level are the most important
      factors. For the rural population, 48.19 per cent to 77.78 per cent of
      inequalities are driven by non-demographic factors. Income and educational
      attainment appear to have a prominent influence on inequality. CONCLUSION: The
      findings suggest that policy targeting the poor, especially the urban poor, is
      needed in order to reduce health inequality.

PMID- 22989201
TI  - Haplotypic association of ADAM33 (T+1, S+1 and V - 3) gene variants in genetic
      susceptibility to asthma in Indian population.
AB  - AIM: The aim of this study was to find out if the ADAM33 gene polymorphisms
      T+1(A>G), S+1(T>A) and V - 3(C>T) and their haplotypes play any role in genetic
      susceptibility to asthma. SUBJECTS AND METHODS: Three hundred and ninety healthy
      controls and 386 asthmatic patients from Lucknow, India, were recruited for the
      study. Subjects were aged between 1-50 years. Among total recruited asthma cases,
      95 (24.6%) had mild intermittent asthma, 235 (60.9%) had mild persistent asthma
      and 56 (14.5%) had moderate persistent asthma. Genotyping was carried out using
      the Polymerase Chain Reaction and Restriction Fragment Length polymorphism
      (PCRRFLP) method. RESULTS: No significant differences in the genotype or allele
      frequencies of ADAM33 gene polymorphisms between asthmatic patients and healthy
      controls were found [p-value>0.05 (All the p-values were Bonferroni corrected)].
      Also, no association of studied SNPs with the severity of the disease asthma was
      observed. However, the TTA haplotype was observed to be associated with asthma
      (OR = 3.4; 95%CI = 1.4-8.7; p = 0.002). CONCLUSIONS: SNPs, T+1, S+1 and V - 3 do
      not individually confer any significant risk of asthma or its severity, but
      haplotype analysis suggests all three polymorphisms together play an important
      role in the disease of asthma.

PMID- 22989202
TI  - Milk kinship hypothesis in light of epigenetic knowledge.
AB  - BACKGROUND: A wet nurse can be used if a baby's natural mother is unable or
      chooses not to breastfeed her infant. The practice of using wet nurses is ancient
      and common to many cultures. PRESENTATION OF THE HYPOTHESIS: We hypothesize that
      infants breastfeeding from the same woman may develop consanguinity even in cases
      in which they are not blood relatives, and that children of two individuals
      breastfed by the same woman may thus be at risk of several genetic diseases
      because of such consanguinity. TESTING THE HYPOTHESIS: Possible evidence for the
      milk kinship hypothesis is to be found in the composition of breast milk, which
      is composed of living substances such as stem cells or substances that can affect
      epigenetic regulation such as microRNAs. IMPLICATIONS OF THE HYPOTHESIS: If these
      epigenetic modifications are heritable, marriages between individuals breastfed
      by the same woman may result in the same consequences as consanguineous
      marriages. In this paper, we attempt to assess this possibility.

PMID- 22989203
TI  - Single molecule magnetoresistance with combined antiferromagnetic and
      ferromagnetic electrodes.
AB  - The magnetoresistance of a hydrogen-phthalocyanine molecule placed on an
      antiferromagnetic Mn(001) surface and contacted by a ferromagnetic Fe electrode
      is investigated using density functional theory based transport calculations and
      low-temperature scanning tunneling microscopy. A large and negative
      magnetoresistance ratio of ~50% is observed in combination with a high
      conductance. The effect originates from a lowest unoccupied molecular orbital
      (LUMO) doublet placed almost in resonance with the Fermi energy. As a
      consequence, irrespective of the mutual alignment of magnetizations, electron
      transport is always dominated by resonant transmission of Mn-majority charge
      carries going through LUMO levels.

PMID- 22989204
TI  - Palladium(II)-catalyzed enantioselective arylation of alpha-imino esters.
AB  - A protocol for Pd(II)-catalyzed asymmetric arylation of N-aryl imino esters has
      been developed. The method affords a practical and direct access to chiral
      arylglycine derivatives in good yields and with high enantioselectivities.

PMID- 22989205
TI  - Superoxide reaction with tyrosyl radicals generates para-hydroperoxy and para
      hydroxy derivatives of tyrosine.
AB  - Tyrosine-derived hydroperoxides are formed in peptides and proteins exposed to
      enzymatic or cellular sources of superoxide and oxidizing species as a result of
      the nearly diffusion-limited reaction between tyrosyl radical and superoxide.
      However, the structure of these products, which informs their reactivity in
      biology, has not been unequivocally established. We report here the complete
      characterization of the products formed in the addition of superoxide, generated
      from xanthine oxidase, to several peptide-derived tyrosyl radicals, formed from
      horseradish peroxidase. RP-HPLC, LC-MS, and NMR experiments indicate that the
      primary stable products of superoxide addition to tyrosyl radical are para
      hydroperoxide derivatives (para relative to the position of the OH in tyrosine)
      that can be reduced to the corresponding para-alcohol. In the case of glycyl
      tyrosine, a stable 3-(1-hydroperoxy-4-oxocyclohexa-2,5-dien-1-yl)-L-alanine was
      formed. In tyrosyl-glycine and Leu-enkephalin, which have N-terminal tyrosines,
      bicyclic indolic para-hydroperoxide derivatives were formed ((2S,3aR,7aR)-3a
      hydroperoxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indole-2-carboxylic acid) by the
      conjugate addition of the free amine to the cyclohexadienone. It was also found
      that significant amounts of the para-OH derivative were generated from the
      hydroxyl radical, formed on exposure of tyrosine-containing peptides to Fenton
      conditions. The para-OOH and para-OH derivatives are much more reactive than
      other tyrosine oxidation products and may play important roles in physiology and
      disease.

PMID- 22989206
TI  - Malignant mixed epithelial and stromal tumor of the kidney: report of the first
      male case.
AB  - Mixed epithelial and stromal tumor of the kidney is a rare benign tumor that
      consists of both epithelial and stromal cells. To date, eight malignant cases
      have previously been reported in female patients only. We report the first case
      of malignant mixed epithelial and stromal tumor of the kidney in a male patient.
      A 67-year-old Japanese man receiving hormonal therapy for prostatic cancer was
      found to have a right renal cystic tumor and underwent right nephrectomy.
      Histologically, the tumor was composed of benign epithelial and stromal cells in
      addition to malignant undifferentiated stromal cells. Immunohistochemically, the
      malignant stromal component was positive for cluster of differentiation 99 and B
      cell lymphoma 2, but no chimeric transcripts for synovial sarcoma were
      identified. Finally, a diagnosis of malignant mixed epithelial and stromal tumor
      of the kidney was recorded. Urologists and pathologists should recognize that
      malignant mixed epithelial and stromal tumors of the kidney might occur in male
      patients receiving hormonal therapy for prostatic cancer.

PMID- 22989207
TI  - Mechanism of feedback allosteric inhibition of ATP phosphoribosyltransferase.
AB  - MtATP-phosphoribosyltransferase catalyzes the first and committed step in l
      histidine biosynthesis in Mycobacterium tuberculosis and is therefore subjected
      to allosteric feedback regulation. Because of its essentiality, this enzyme is
      being studied as a potential target for novel anti-infectives. To understand the
      basis for its regulation, we characterized the allosteric inhibition using gel
      filtration, steady-state and pre-steady-state kinetics, and the pH dependence of
      inhibition and binding. Gel filtration experiments indicate that MtATP
      phosphoribosyltransferase is a hexamer in solution, in the presence or absence of
      l-histidine. Steady-state kinetic studies demonstrate that l-histidine inhibition
      is uncompetitive versus ATP and noncompetitive versus PRPP. At pH values close to
      neutrality, a K(ii) value of 4 MUM was obtained for l-histidine. Pre-steady-state
      kinetic experiments indicate that chemistry is not rate-limiting for the overall
      reaction and that l-histidine inhibition is caused by trapping the enzyme in an
      inactive conformation. The pH dependence of binding, obtained by nuclear magnetic
      resonance, indicates that l-histidine binds better as the neutral alpha-amino
      group. The pH dependence of inhibition (K(ii)), on the contrary, indicates that l
      histidine better inhibits MtATP-phosphoribosytransferase with a neutral imidazole
      and an ionized alpha-amino group. These results are combined into a model that
      accounts for the allosteric inhibition of MtATP-phosphoribosyltransferase.

PMID- 22989208
TI  - Health professionals' perspectives on information provision for patients with
      brain tumours and their families.
AB  - A significant number of patients diagnosed with primary brain tumours report
      unmet information needs. Using concept mapping methodology, this study aimed to
      identify strategies for improving information provision, and to describe factors
      that health professionals understood to influence their provision of information
      to patients with brain tumours and their families. Concept mapping is a mixed
      methods approach that uses statistical methods to represent participants'
      perceived relationships between elements as conceptual maps. These maps, and
      results of associated data collection and analyses, are used to extract concepts
      involved in information provision to these patients. Thirty health professionals
      working across a range of neuro-oncology roles and settings participated in the
      concept mapping process. Participants rated a care coordinator as the most
      important strategy for improving brain tumour care, with psychological support as
      a whole rated as the most important element of care. Five major themes were
      identified as facilitating information provision: health professionals'
      communication skills, style and attitudes; patients' needs and preferences;
      perceptions of patients' need for protection and initiative; rapport and
      continuity between patients and health professionals; and the nature of the
      healthcare system. Overall, health professionals conceptualised information
      provision as 'individualised', dependent on these interconnected personal and
      environmental factors.

PMID- 22989209
TI  - Resolution of Hypoprothrombinemia-Lupus Anticoagulant Syndrome (HLAS) after
      multidrug therapy with rituximab: a case report and review of the literature.
AB  - Hypoprothrombinemia associated with a lupus anticoagulant (LA) was first reported
      in the literature over 50 years ago. The hypoprothrombinemia-lupus anticoagulant
      syndrome (HLAS) is a rare bleeding diathesis that has been associated with LAs in
      adult and paediatric patients with systemic lupus erythematosus (SLE) and with
      transient LAs due to other causes. There are no standard recommendations for
      treating haemorrhage associated with this syndrome. Herein, we report a patient
      with SLE and HLAS who achieved a durable remission following treatment with
      intravenous immune globulin (IVIG), prednisone and rituximab.

PMID- 22989210
TI  - Brain-derived neurotrophic factor genotype is associated with brain gray and
      white matter tissue volumes recovery in abstinent alcohol-dependent individuals.
AB  - Neuroimaging studies have linked the methionine (Met) allele of the brain-derived
      neurotrophic factor (BDNF) gene to abnormal regional brain volumes in several
      psychiatric and neurodegenerative diseases. However, no neuroimaging studies
      assessed the effects of this allele on brain morphology in alcohol use disorders
      and its demonstrated change during abstinence from alcohol. Here we assessed the
      effects of the BDNF Val66Met (rs6265) polymorphism on regional brain tissue
      volumes and their recovery during short-term abstinence in treatment-seeking
      alcohol-dependent individuals. 3D T1 weighted magnetic resonance images from 62
      individuals were acquired at 1.5 T at one week of abstinence from alcohol; 41 of
      the participants were rescanned at 5 weeks of abstinence. The images were
      segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid and
      parcellated into regional volumes. The BDNF genotype was determined from blood
      samples using the TaqMan technique. Alcohol-dependent Val (Valine)/Met
      heterozygotes and Val homozygotes had similar regional brain volumes at either
      time point. However, Val homozygotes had significant GM volume increases, while
      Val/Met heterozygotes increased predominantly in WM volumes over the scan
      interval. Longitudinal increases in GM but not WM volumes were related to
      improvements in neurocognitive measures during abstinence. The findings suggest
      that functionally significant brain tissue volume recovery during abstinence from
      alcohol is influenced by BDNF genotype.

PMID- 22989212
TI  - Scanning structure-activity relationships with structure-activity similarity and
      related maps: from consensus activity cliffs to selectivity switches.
AB  - Systematic description of structure-activity relationships (SARs) of data sets
      and structure-property relationships (SPRs) is of paramount importance in
      medicinal chemistry and other research fields. To this end, structure-activity
      similarity (SAS) maps are one of the first tools proposed to describe SARs using
      the concept of activity landscape modeling. One of the major goals of the SAS
      maps is to identify activity cliffs defined as chemical compounds with high
      similar structure but unexpectedly very different biological activity. Since the
      first publication of the SAS maps more than ten years ago, these tools have
      evolved and adapted over the years to analyze various types of compound
      collections, including structural diverse and combinatorial sets with activity
      for one or multiple biological end points. The development of SAS maps has led to
      general concepts that are applicable to other activity landscape methods such as
      "consensus activity cliffs" (activity cliffs common to a series of
      representations or descriptors) and "selectivity switches" (structural changes
      that completely invert the selectivity pattern of similar compounds against two
      biological end points). Herein, we review the development, practical
      applications, limitations, and perspectives of the SAS and related maps which are
      intuitive and powerful informatics tools to computationally analyze SPRs.

PMID- 22989211
TI  - Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156
      controlled gene network.
AB  - BACKGROUND: The Arabidopsis microRNA156 (miR156) regulates 11 members of the
      SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to
      complementary target mRNAs. Each SPL gene further regulates a set of other genes;
      thus, miR156 controls numerous genes through a complex gene regulation network.
      Increased axillary branching occurs in transgenic Arabidopsis overexpressing
      miR156b, similar to that observed in loss-of-function max3 and max4 mutants with
      lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to
      enhance carotenoid levels and reproductive shoot branching when expressed in
      Brassica napus, suggesting a link between miR156b expression and carotenoid
      metabolism. However, details of the miR156 regulatory network of SPL genes
      related to carotenoid metabolism are not known. RESULTS: In this study, an
      Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered
      branching and trichome morphology and increased seed carotenoid levels compared
      to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S
      enhancers present on the T-DNA insert was responsible for these phenotypes.
      Constitutive and leaf primodium-specific expression of a miR156-insensitive
      (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant
      morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15
      (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT
      phenotype in sk156. Our findings suggest that SPL15 function is somewhat
      redundant with other SPL family members, which collectively affect plant
      phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156
      expressing SPL15m, together with the presence of multiple repeats of SPL-binding
      GTAC core sequence close to the miR156b transcription start site, suggested
      feedback regulation of miR156b expression by SPL15. This was supported by the
      demonstration of specific in vitro interaction between DNA-binding SBP domain of
      SPL15 and the proximal promoter sequence of miR156b. CONCLUSIONS: Enhanced
      miR156b expression in sk156 leads to the mutant phenotype including carotenoid
      levels in the seed through suppression of SPL15 and other SPL target genes.
      Moreover, SPL15 has a regulatory role not only for downstream components, but
      also for its own upstream regulator miR156b.

PMID- 22989213
TI  - IL-17A in the tumor microenvironment of the human colorectal adenoma-carcinoma
      sequence.
AB  - OBJECTIVES: Interleukin (IL)-17A is an important pro-inflammatory cytokine and
      involved in the colorectal carcinogenesis. In this study, the authors evaluated
      the dynamic change of IL-17A expression in the tumor microenvironment throughout
      the colorectal adenoma-carcinoma sequence. MATERIALS & METHODS: Using
      quantitative real-time PCR (polymerase chain reaction) and semi-quantitative
      immunohistochemistry, the authors examined the expression level of IL-17A in 50
      of human colorectal adenoma tissues, 50 of colorectal cancer (CRC) tissues and 15
      controls. The relationship between IL-17A expression and clinicopathological
      parameters throughout the sequence was also evaluated. RESULTS: The results
      revealed a step-up increased IL-17A mRNA level throughout the colorectal adenoma
      carcinoma sequence, which began to increase in the adenomas and became even
      higher in the CRCs; notably, the increase of IL-17A mRNA level in the adenomatous
      tissues was associated with the severity of dysplasia. Immunohistochemical
      analysis confirmed the real-time PCR results and revealed gradually increasing IL
      17A cells in both the stroma and adenomatous/cancerous epithelium. In addition,
      the quantitative real-time PCR result has also revealed an increased expression
      of TH17-stimulating factors throughout the sequence. CONCLUSIONS: IL-17A and TH17
      are highly activated throughout the colorectal adenoma-carcinoma sequence.

PMID- 22989215
TI  - Recurrent laryngeal nerve injury in thyroid surgery: a review.
AB  - Recurrent laryngeal nerve palsy (RLNP) is an important and potentially
      catastrophic complication of thyroid surgery. Permanent RLNP occurs in 0.3-3% of
      cases, with transient palsies in 5-8%. A literature review and analysis of recent
      data regarding RLNP in thyroid surgery was performed, with particular focus on
      the identification of high-risk patients, the role of intraoperative
      identification and dissection of the nerve, and the role of intraoperative
      neuromonitoring (IONM) and optimal perioperative nerve assessment. In conjunction
      with the review, data from the Monash University/Alfred Hospital Endocrine
      Surgery Unit between January 2007 and October 2011 were retrospectively analysed,
      including 3736 consecutive nerves at risk (NAR). The current literature and our
      data confirm that patients undergoing re-operative thyroid surgery and thyroid
      surgery for malignancies are at increased risk of RLNP. Intraoperative
      visualization and capsular dissection of the RLN remain the gold standard for
      intraoperative care during thyroid surgery for reducing RLNP risk. IONM should
      not be used as the sole mechanism for identifying and preserving the nerve,
      although it can be used to aid in the identification and dissection of the nerve,
      and may aid in nerve protection in high-risk cases including cancer surgery and
      re-operative surgery.

PMID- 22989216
TI  - Skin temperature changes following sciatic nerve injury in rats.
AB  - In the clinical setting, skin temperature is both easily evaluated and useful in
      assessments of sympathetic dysfunction. The present study purposed to observe the
      serial skin temperature changes of both hindlimbs following several types of
      sciatic nerve injury (complete transection and ligation model [CTL], crush injury
      model [CRI], and chronic constriction injury model [CCI]) in Sprague-Dawley rats
      and, further, to delineate the possible mechanisms through various evaluation
      methods. The temperature differences between the intact and injured areas
      (DeltaT) on the plantar surface and toes varied among the CTL, CRI, and CCI
      injury models during the acute stage (7 days post-injury). During the subacute to
      chronic stages (7-28 days post-injury), DeltaT on the plantar area and toes of
      the CCI model were higher than those of the CTL and CRI models. The sciatic
      functional index was gradually restored in the CRI and CCI models, but was
      unchanged in the CTL model. The CTL model showed constant hypoesthesia; the CRI
      model, contrastingly, was restored to normal, and the CCI model showed gradual
      hyperesthesia until 28 days post-injury. The latency and amplitude of the
      compound muscle action potential (CMAP) in the involved plantar muscle was not
      found in the CTL group 4 weeks post-injury, but showed gradual restoration in the
      CRI and CCI models. Regression analysis revealed that the DeltaT in the plantar
      area and toes were affected only by the CMAP amplitude in the involved plantar
      muscle; therefore, it can be said that the skin temperature on the injured area
      after sciatic nerve injury was influenced by the functional status of the
      involved muscle. Measurement of skin temperature can differentiate mild
      peripheral nerve injury from moderate-to-severe injuries, although its clinical
      significance might be limited.

PMID- 22989217
TI  - Ferroelectric and magnetic properties of Nd-doped Bi4 - xFeTi3O12 nanoparticles
      prepared through the egg-white method.
AB  - Multiferroic behavior of Bi4 - xNdxFeTi3O12 (0.0 <= * <= 0.25, * = 0.05) ceramic
      nanoparticles prepared through the egg-white method was investigated. The
      dielectric properties of the samples show normal behavior and are explained in
      the light of space charge polarization. Room temperature polarization-electric
      field (P-E) curves show that the samples are not saturated with maximum remanence
      polarization, Pr = 0.110 MUC/cm2, and a relatively low coercive field, Ec = of
      7.918 kV/cm, at an applied field of 1 kV/cm was observed for 5% Nd doping. The
      room temperature M-H hysteresis curve shows that the samples exhibit intrinsic
      antiferromagnetism with a weak ferromagnetism. These properties entitle the grown
      nanoparticles of BNFT as one of the few multiferroic materials that exhibit
      decent magnetization and electric polarization.

PMID- 22989218
TI  - Detection and monitoring of neurotransmitters--a spectroscopic analysis.
AB  - OBJECTIVES: We demonstrate that confocal Raman mapping spectroscopy provides
      rapid, detailed, and accurate neurotransmitter analysis, enabling millisecond
      time resolution monitoring of biochemical dynamics. As a prototypical
      demonstration of the power of the method, we present real-time in vitro
      serotonin, adenosine, and dopamine detection, and dopamine diffusion in an
      inhomogeneous organic gel, which was used as a substitute for neurologic tissue.
      MATERIALS AND METHODS:  Dopamine, adenosine, and serotonin were used to prepare
      neurotransmitter solutions in distilled water. The solutions were applied to the
      surfaces of glass slides, where they interdiffused. Raman mapping was achieved by
      detecting nonoverlapping spectral signatures characteristic of the
      neurotransmitters with an alpha 300 WITec confocal Raman system, using 532 nm
      neodymium-doped yttrium aluminum garnet laser excitation. Every local Raman
      spectrum was recorded in milliseconds and complete Raman mapping in a few
      seconds. RESULTS:  Without damage, dyeing, or preferential sample preparation,
      confocal Raman mapping provided positive detection of each neurotransmitter,
      allowing association of the high-resolution spectra with specific microscale
      image regions. Such information is particularly important for complex,
      heterogeneous samples, where changes in composition can influence
      neurotransmission processes. We also report an estimated dopamine diffusion
      coefficient two orders of magnitude smaller than that calculated by the flow
      injection method. CONCLUSIONS:  Accurate nondestructive characterization for real
      time detection of neurotransmitters in inhomogeneous environments without the
      requirement of sample labeling is a key issue in neuroscience. Our work
      demonstrates the capabilities of Raman spectroscopy in biological applications,
      possibly providing a new tool for elucidating the mechanism and kinetics of deep
      brain stimulation.

PMID- 22989219
TI  - Nanoparticle-mediated remote control of enzymatic activity.
AB  - Nanomaterials have found numerous applications as tunable, remotely controlled
      platforms for drug delivery, hyperthermia cancer treatment, and various other
      biomedical applications. The basis for the interest lies in their unique
      properties achieved at the nanoscale that can be accessed via remote stimuli.
      These properties could then be exploited to simultaneously activate secondary
      systems that are not remotely actuatable. In this work, iron oxide nanoparticles
      are encapsulated in a bisacrylamide cross-linked polyacrylamide hydrogel network
      along with a model dehalogenase enzyme, L-2-HAD(ST). This thermophilic enzyme is
      activated at elevated temperatures and has been shown to have optimal activity at
      70  degrees C. By exposing the Fe(3)O(4) nanoparticles to a remote stimulus, an
      alternating magnetic field (AMF), enhanced system heating can be achieved, thus
      remotely activating the enzyme. The internal heating of the nanocomposite
      hydrogel network in the AMF results in a 2-fold increase in enzymatic activity as
      compared to the same hydrogel heated externally in a water bath, suggesting that
      the internal heating of the nanoparticles is more efficient than the diffusion
      limited heating of the water bath. This system may prove useful for remote
      actuation of biomedical and environmentally relevant enzymes and find
      applications in a variety of fields.

PMID- 22989220
TI  - Language dominance in translation priming: evidence from balanced and unbalanced
      Chinese-English bilinguals.
AB  - It is well established in the masked translation priming literature that the
      priming effect is sensitive to language direction with noncognates-namely, the
      priming effect is consistently observed from first language (L1) to second
      language (L2), but not always from L2 to L1. Several recent reports demonstrated
      both L1-L2 and L2-L1 priming and attributed the restoration of L2-L1 priming to
      high proficiency in L2. Here, the current study tested two groups of highly
      proficient Chinese-English bilinguals, with one group more dominant in English
      and the other more balanced in both languages. The L2-L1 priming effect was only
      observed with the balanced bilinguals, but not the English-dominant ones. Based
      on these results, I argue that the language proficiency account is not sufficient
      to explain the priming asymmetry and that the relative bilingual balance is a
      more accurate account. Theoretically, the cross-language balance is determined by
      the representational difference between L1 and L2 at the semantic level. I
      discuss the results in relation to various bilingual models, in particular, the
      sense model and the distributional representational model (DRM), which capture
      the semantic representations of bilinguals.

PMID- 22989222
TI  - A discussion of HIV/AIDS family interventions: implications for family-focused
      nursing practice.
AB  - AIM: This article presents a discussion on the role of family interventions in
      HIV/AIDS disease prevention and care. BACKGROUND: Although HIV/AIDS epidemic and
      its impact on the society traditionally has been measured in terms of individual
      risk behaviours and individual-level HIV prevention, HIV/AIDS family-focused
      prevention and management strategies are increasingly becoming a priority.
      However, little is known as to what constitutes a HIV/AIDS family intervention.
      DATA SOURCES: The search was limited to English and published literature starting
      in the year 1983 to date. CINAHL and PubMed were emphasized using a combination
      of text words and subject headings. Cochrane Library, PsycInfo, Scopus, and the
      ISI Web of Science databases were also searched using keywords and in the case of
      PsycInfo, subject headings were used. The main keywords were 'nurse', or
      'nursing', 'HIV/AIDS', 'family interventions', 'family support' and 'family
      education', and/or 'family subsystems'. DISCUSSION: The process of theorizing
      about 'family interventions' and 'HIV/AIDS-family interventions' is critical for
      putting forth essential components unique for designing culturally specific
      HIV/AIDS family interventions. In addition, any proposed design of HIV/AIDS
      family intervention should consider the impact of HIV/AIDS on the family across
      the family life span, disease trajectory, and from an interdisciplinary
      perspective. CONCLUSION: Training needs of family nurses should be met when
      designing multidisciplinary HIV/AIDS-FIs. Furthermore, nurses should be proactive
      in advocating for HIV/AIDS family intervention and HIV/AIDS family policies to
      improve outcomes in family functioning, processes, and relationships. More needs
      to be done in regard to research on families, family interventions,
      effectiveness, and cost of family-focused approaches.

PMID- 22989221
TI  - Histology of symptomatic gastroesophageal reflux disease: is it predictive of
      response to proton pump inhibitors?
AB  - BACKGROUND AND AIM: To examine the differences in esophageal histopathology
      between non-erosive reflux disease (NERD) and reflux esophagitis (RE), and to
      investigate whether baseline esophageal histopathology can predict the
      therapeutic response to proton pump inhibitors (PPIs). METHOD: The subjects
      comprised 94 patients with NERD (n = 71) or mild RE (n = 23). Tissue was biopsied
      from 5 cm above the squamo-columnar junction (SCJ), and the degree or presence of
      nine histopathological markers was assessed. The patients were treated with
      rabeprazole (RPZ) 10 mg once daily for 4 weeks. If complete heartburn relief was
      not achieved, RPZ was increased to 10 mg twice daily for another 2 weeks, and
      then to 20 mg twice daily for another 2 weeks if heartburn remained. RESULTS:
      Features of esophageal histopathology 5 cm above the SCJ differed between NERD
      and RE patients. The esophageal histopathology in patients unresponsive to RPZ
      was characterized by Protein Gene Product (PGP) 9.5 negativity in those with
      NERD, and intraepithelial bleeding in those with RE. In addition, the combination
      of dilated intercellular spaces (DIS) (+)/PGP 9.5 (-) was indicative of strong
      resistance to PPI therapy in NERD patients. CONCLUSION: The therapeutic efficacy
      of PPI can be predicted from the features of biopsied esophageal tissue. Factors
      predictive of resistance to treatment with PPI are negativity for PGP 9.5 in NERD
      patients and intraepithelial bleeding in RE patients.

PMID- 22989223
TI  - Medical simulation technology: educational overview, industry leaders, and what's
      missing.
AB  - Modern medical simulation technology (MST) debuted in 1960 with the development
      of Resusci Annie (Laerdal 2007), which assisted students in the acquisition of
      proper ventilation and compression techniques used during basic life support.
      Following a steady stream of subsequent technological advances and innovations,
      MST manufacturers are now able to offer training aids capable of facilitating
      innovative learning in such diverse areas as human patient simulators, simulated
      clinical environments, virtual procedure stations, virtual medical environments,
      electronic tutors, and performance recording. The authors list a number of the
      most popular MSTs presently available while citing evaluative efforts undertaken
      to date regarding the efficacy of MST to the medical profession. They conclude by
      proposing a variety of simulation innovations of prospective interest to both
      medical and technology personnel while offering healthcare administrators a
      series of recommended considerations when planning to integrate MST into existing
      medical systems.

PMID- 22989225
TI  - Organizational citizenship behavior and work experience.
AB  - The authors compared the relationship of elements of the Organizational
      Citizenship Behavior (OCB) and years of work experience of registered nurses in
      the state of Texas. Work experience research has shown a relationship between OCB
      and work experience through mediating roles of various work related
      characteristics does exist. Work experience is described as the overall length of
      time in an occupation or workforce. Civic virtue was the only element of
      organizational citizenship behavior to have a statistically significant
      correlation with years of work experience in this study. Other elements were
      found to have no statistically significant correlation with years of work
      experience. Further research should be undertaken to determine if correlations
      between these two constructs holds up when the population under study is further
      refined by job classification, such as management and staff, or industry segment.

PMID- 22989224
TI  - 'Phantom networks' of managed behavioral health providers: an empirical study of
      their existence and effect on patients in two New Jersey counties.
AB  - Managed care organizations often tout the availability of clinicians in their
      provider networks, yet their clients seeking mental healthcare may find it
      difficult to obtain such care in a timely and effective manner. Using
      comprehensive data from two counties in New Jersey, the authors examine the
      prevalence of phantom networks of managed care providers of behavioral health
      services and the effects of such networks on patients' wait times and the
      availability of therapists treating children.

PMID- 22989226
TI  - Lack of access in healthcare delivery: a model for using dental hygienists in a
      cost effective manner to help address the oral healthcare problem.
AB  - The healthcare delivery of the United States is confronted with many issues and
      problems. In an attempt to deal with them, the country has been engaged in a
      process of healthcare reform. Unfortunately, this reform has largely focused on
      who is going to pay, what is going to be covered, and how all of the
      constituencies are hopefully going to be satisfied. What have been largely
      unaddressed are new delivery paradigms or how the care will be distributed to the
      underserved. The authors attempt to seek solutions to these last two areas of
      concern. They spell out how the expansion of the scope of practice for dental
      hygienists will allow them to bridge the gaps in service and to help deliver
      dental coverage and elements of systemic healthcare to underserved populations.
      Finally, the authors provide the steps and mechanisms of how the scope of
      practice can be expanded. Policy and educational requirements are considered.

PMID- 22989227
TI  - Metabolization of the bacteriostatic agent triclosan in edible plants and its
      consequences for plant uptake assessment.
AB  - Persistent environmental contaminants may enter agricultural fields via the
      application of sewage sludge, by irrigation with treated municipal wastewater or
      by manuring. It has been shown that such contaminants can be incorporated into
      crop plants. The metabolism of the bacteriostatic agents triclocarban, triclosan,
      and its transformation product methyl triclosan was investigated after their
      uptake into carrot cell cultures. A fast metabolization of triclosan was observed
      and eight so far unknown phase II metabolites, conjugates with saccharides,
      disaccharides, malonic acid, and sulfate, were identified by liquid
      chromatography-mass spectrometry. Triclocarban and methyl triclosan lack a
      phenolic group and remained unaltered in the cell cultures. Phase I
      metabolization was not observed for any of the compounds. All eight triclosan
      conjugates identified in the cell cultures were also detected in extracts of
      intact carrot plants cultivated on triclosan contaminated soils. Their total
      amount in the plants was assessed to exceed the amount of the triclosan itself by
      a factor of 5. This study shows that a disregard of conjugates in studies on
      plant uptake of environmental contaminants may severely underestimates the extent
      of uptake into plants and, eventually, the potential human exposure to
      contaminants via food of plant origin.

PMID- 22989228
TI  - Segmental arterial mediolysis accompanied by renal infarction and pancreatic
      enlargement: a case report.
AB  - INTRODUCTION: Due to recent advances in imaging diagnostic techniques, there are
      an increasing number of case reports of segmental arterial mediolysis. However,
      there are only a limited number of reports on segmental arterial mediolysis
      related abnormalities of abdominal organs other than the intestine. This report
      describes a case of segmental arterial mediolysis accompanied by abnormalities of
      abdominal organs without clinical symptoms. CASE PRESENTATION: A 52-year-old
      Japanese man with hematuria and no prior medical history was referred to a
      urologist and was diagnosed as having urinary bladder cancer. He underwent trans
      urethral resection of the bladder tumor and intra-vesical instillation therapy,
      which was followed by observation. During follow-up, although no abdominal
      symptoms were observed, an abdominal computed tomography scan revealed a
      dissection of the superior mesenteric artery. A false lumen partially occluded by
      a thrombus was located distal to this occlusion. The lumen was irregularly shaped
      with narrow and wide sections. Similar irregularities were also observed in the
      wall of the inferior mesenteric artery. Arterial dissection with thromboembolism
      in the left renal artery and renal infarction was also observed. Follow-up
      computed tomography after two months revealed an enlargement of the pancreatic
      tail adjacent to the splenic artery. Follow-up three-dimensional computed
      tomography showed gradual  re-expansion of the true lumen of the superior
      mesenteric artery, improvement in arterial wall irregularities, and a reduction
      in the pancreas enlargement and renal infarction. Over the following 15 months,
      these changes gradually normalized. On the basis of the vascular changes in
      multiple arterial systems that resolved spontaneously, we considered that the
      lesions were associated with segmental arterial mediolysis. CONCLUSIONS: We
      present a rare case of segmental arterial mediolysis accompanied by abnormalities
      of abdominal organs without clinical symptoms. Three-dimensional computed
      tomography was useful for follow-up evaluation in our patient.

PMID- 22989229
TI  - Effects of PAR and UV-B radiation on herbal yield, bioactive compounds and their
      antioxidant capacity of some medicinal plants under controlled environmental
      conditions.
AB  - Photosynthetically active radiation (PAR) and Ultraviolet B (UV-B) radiation are
      among the main environmental factors acting on herbal yield and biosynthesis of
      bioactive compounds in medicinal plants. The objective of this study was to
      evaluate the influence of biologically effective UV-B light (280-315 nm) and PAR
      (400-700 nm) on herbal yield, content and composition, as well as antioxidant
      capacity of essential oils and polyphenols of lemon catmint (Nepeta cataria L. f.
      citriodora), lemon balm (Melissa officinalis L.) and sage (Salvia officinalis L.)
      under controlled greenhouse cultivation. Intensive UV-B radiation (2.5 kJ m(-2) 
      d(-1) ) influenced positively the herbal yield. The essential oil content and
      composition of studied herbs were mainly affected by PAR and UV-B radiation. In
      general, additional low-dose UV-B radiation (1 kJ m(-2) d(-1) ) was most
      effective for biosynthesis of polyphenols in herbs. Analysis of major
      polyphenolic compounds provided differences in sensitivity of main polyphenols to
      PAR and UV-B radiation. Essential oils and polyphenol-rich extracts of radiated
      herbs showed essential differences in antioxidant capacity by the ABTS system.
      Information from this study can be useful for herbal biomass and secondary
      metabolite production with superior quality under controlled environment
      conditions.

PMID- 22989230
TI  - Initial Japanese experience with the LAP-BAND system.
AB  - INTRODUCTION: Laparoscopic bariatric surgery has gradually spread in Japan since
      it was introduced in 2000. In 2005, we introduced laparoscopic adjustable gastric
      banding (LAGB) with the LAP-BAND system into Japan. Here, we evaluate our
      intermediate-term results with the LAP-BAND system. METHODS: Between August 2005
      and June 2010, 27 Japanese patients with morbid obesity (BMI >= 35 kg/m(2) )
      underwent LAGB with the LAP-BAND system in our institution. Our patients' average
      weight was 111 kg and BMI was 41 kg/m(2) . All LAGB procedures were performed
      through the pars flaccida pathway with band fixation using gastric-to-gastric
      sutures. The average follow-up period was 48 months. RESULTS: All procedures were
      completed laparoscopically. One early complication (sudden cardiac arrest due to
      postoperative bleeding) and three late complications (port trouble,
      megaesophagus, and band slippage) were experienced, and reoperations were
      performed in three of the patients. Weight loss and percentage of excess weight
      loss on average were 26 kg and 53% after 3 years and 22 kg and 53% after 6 years,
      respectively. In line with this good weight loss, comorbidities, especially those
      of type 2 diabetes and metabolic syndrome were frequently resolved or improved.
      CONCLUSION: LAGB with the LAP-BAND system appears to be beneficial in obese
      Japanese patients.

PMID- 22989231
TI  - The effect of the UP4FUN pilot intervention on objectively measured sedentary
      time and physical activity in 10-12 year old children in Belgium: the ENERGY
      project.
AB  - BAKCKGROUND: The first aim was to examine the effect of the UP4FUN pilot
      intervention on children's total sedentary time. The second aim was to
      investigate if the intervention had an effect on children's physical activity
      (PA) level. Finally, we aimed to investigate demographic differences (i.e. age,
      gender, ethnicity, living status and having siblings) between children in the
      intervention group who improved in sedentary time and PA at post-test and
      children in the intervention group who worsened in sedentary time and PA at post
      test. METHODS: The six weeks UP4FUN intervention was tested in a randomized
      controlled trial with pre-test post-test design with five intervention and five
      control schools in Belgium and included children of the 5th and 6th grade. The
      children wore accelerometers for seven days at pre- and post-test. Analyses
      included children with valid accelerometer data for at least two weekdays with
      minimum 10h-wearing time and one weekend day with 8h-wearing time. RESULT: Final
      analyses included 372 children (60% girls, mean age = 10.9 +/- 0.7 years). There
      were no significant differences in the change in sedentary time or light PA
      between intervention and control schools for the total sample or for the subgroup
      analyses by gender. However, children (specifically girls) in the intervention
      group had a higher decrease in moderate-to-vigorous PA than children in the
      control group. In the intervention group, children who lived with both parents
      and children with one or more siblings were less likely to reduce sedentary time
      after exposure to the intervention. Older children, girls and children who lived
      with both parents were less likely to increase light PA after the intervention.
      CONCLUSION: The UP4FUN intervention did not result in an effect on children's
      sedentary time. Based on the high amounts of accelerometer-derived sedentary time
      in this age group, more efforts are needed to develop strategies to reduce
      children's sedentary time.

PMID- 22989232
TI  - IGF2/H19 hypomethylation is tissue, cell, and CpG site dependent and not
      correlated with body asymmetry in adolescents with Silver-Russell syndrome.
AB  - BACKGROUND: Silver-Russell syndrome (SRS) is characterized by severe
      intrauterine and postnatal growth failure and frequent body asymmetry. Half of
      the patients with SRS carry a DNA hypomethylation of the imprinting center region
      1 (ICR1) of the insulin-like growth factor 2 (IGF2)/H19 locus, and the clinical
      phenotype is most severe in these patients. We aimed to elucidate the epigenetic
      basis of asymmetry in SRS and the cellular consequences of the ICR1
      hypomethylation. RESULTS: The ICR1 methylation status was analyzed in blood and
      in addition in buccal smear probes and cultured fibroblasts obtained from punch
      biopsies taken from the two body halves of 5 SRS patients and 3 controls. We
      found that the ICR1 hypomethylation in SRS patients was stronger in blood
      leukocytes and oral mucosa cells than in fibroblasts. ICR1 CpG sites were
      affected differently. The severity of hypomethylation was not correlated to body
      asymmetry. IGF2 expression and IGF-II secretion of fibroblasts were not
      correlated to the degree of ICR1 hypomethylation. SRS fibroblasts responded well
      to stimulation by recombinant human IGF-I or IGF-II, with proliferation rates
      comparable with controls. Clonal expansion of primary fibroblasts confirmed the
      complexity of the cellular mosaicism. CONCLUSIONS: We conclude that the ICR1
      hypomethylation SRS is tissue, cell, and CpG site specific. The correlation of
      the ICR1 hypomethylation to IGF2 and H19 expression is not strict, may depend on
      the investigated tissue, and may become evident only in case of more severe
      methylation defects. The body asymmetry in juvenile SRS patients is not related
      to a corresponding ICR1 hypomethylation gradient, rendering more likely an
      intrauterine origin of asymmetry. Overall, it may be instrumental to consider not
      only the ICR1 methylation status as decisive for IGF2/H19 expression regulation.

PMID- 22989233
TI  - Glycine rescue of beta-sheets from cis-proline.
AB  - Proline is incompatible with ideal beta-sheet geometry, and the incompatibility
      gets magnified when Pro assumes the cis peptidyl-prolyl conformation. We show
      that Gly appears with high propensity at pre-cisPro positions in beta-sheets and
      rescues the beta-sheet from severe distortions by assuming a right-handed
      polyproline conformation (beta(PR)), effectively increasing the local beta-sheet
      register by one residue. The united residue, Gly(beta(PR))-cisPro, is
      evolutionarily conserved, functionally important, and dynamic in nature.

PMID- 22989234
TI  - Consensus recommendations for the use of FEIBA((r))  in haemophilia A patients
      with inhibitors undergoing elective orthopaedic and non-orthopaedic surgery.
AB  - A growing number of publications have described the efficacy and safety of FEIBA
      as a first-line haemostatic agent for surgical procedures in haemophilia A
      patients with high-responding FVIII inhibitors. The aim of this study was to
      provide practical guidance on patient management and selection and also to
      communicate a standardized approach to the dosing and monitoring of FEIBA during
      and after surgery. A consensus group was convened with the aims of (i) providing
      an overview of the efficacy and safety of FEIBA in surgery; (ii) sharing best
      practice; (iii) developing recommendations based on the outcome of (i) and (ii).
      To date there have been 17 publications reporting on the use of FEIBA in over 210
      major and minor orthopaedic and non-orthopaedic surgical procedures. Haemostatic
      outcome was rated as 'excellent' or 'good' in 78-100% of major cases. The
      reporting of thromboembolic complications or anamnestic response to FEIBA was
      very rare. Key to the success of FEIBA as haemostatic cover in surgery is to
      utilize the preplanning phase to prepare the patient both for surgery and also
      for rehabilitation. Haemostatic control with FEIBA should be continued for an
      adequate period postoperatively to support wound healing and to cover what can in
      some patients be an extended period of physiotherapy. Published data have
      demonstrated that FEIBA can provide adequate, well tolerated, peri and
      postoperative haemostatic cover for a variety of major and minor surgical
      procedures in patients with haemophilia A. The consensus recommendations provide
      a standardized approach to the dosing and monitoring of FEIBA.

PMID- 22989235
TI  - Farnesyl diphosphate analogues with aryl moieties are efficient alternate
      substrates for protein farnesyltransferase.
AB  - Farnesylation is an important post-translational modification essential for the
      proper localization and function of many proteins. Transfer of the farnesyl group
      from farnesyl diphosphate (FPP) to proteins is catalyzed by protein
      farnesyltransferase (FTase). We employed a library of FPP analogues with a range
      of aryl groups substituting for individual isoprene moieties to examine some of
      the structural and electronic properties of the transfer of an analogue to the
      peptide catalyzed by FTase. Analysis of steady-state kinetics for modification of
      peptide substrates revealed that the multiple-turnover activity depends on the
      analogue structure. Analogues in which the first isoprene is replaced with a
      benzyl group and an analogue in which each isoprene is replaced with an aryl
      group are good substrates. In sharp contrast with the steady-state reaction, the
      single-turnover rate constant for dansyl-GCVLS alkylation was found to be the
      same for all analogues, despite the increased chemical reactivity of the benzyl
      analogues and the increased steric bulk of other analogues. However, the single
      turnover rate constant for alkylation does depend on the Ca(1)a(2)X peptide
      sequence. These results suggest that the isoprenoid transition-state conformation
      is preferred over the inactive E.FPP.Ca(1)a(2)X ternary complex conformation.
      Furthermore, these data suggest that the farnesyl binding site in the exit groove
      may be significantly more selective for the farnesyl diphosphate substrate than
      the active site binding pocket and therefore might be a useful site for the
      design of novel inhibitors.

PMID- 22989236
TI  - Statin use is associated with a reduction in the incidence of esophageal
      adenocarcinoma: a case control study.
AB  - The incidence of esophageal adenocarcinoma (EAC) is increasing significantly
      throughout the developed world. As yet, there are no proven chemopreventive
      strategies. In laboratory studies, aspirin, non-steroidal anti-inflammatory drugs
      and statins have promising chemopreventive actions. Several observational studies
      support a protective effect of aspirin and non-steroidal anti-inflammatory drugs,
      but there are only limited clinical data exploring the potential protective
      effect of statins. We conducted a case-control study examining aspirin and statin
      use in patients with EAC. Cancer cases were compared against age-sex-matched
      controls attending for diagnostic upper gastrointestinal endoscopy. Risk factor
      and drug exposure were established using standardized interviews. Logistic
      regression was used to compare statin exposure and correct for confounding
      factors. A total of 112 cases and 448 controls were enrolled. Statin use was
      associated with a significantly lower incidence of EAC (odds ratio 0.52, 95%
      confidence interval 0.27-0.92). Aspirin use was also associated with apparent
      protection against EAC (odds ratio 0.68, 95% confidence interval 0.28-0.92), and
      a significantly greater effect was seen with the combination of statin plus
      aspirin (odds ratio 0.27, 95% confidence interval 0.05-0.67). There was a
      significant trend for greater risk reduction with longer duration and higher
      doses of statin use. Simvastatin comprised the majority of statin use, but
      similar effects were seen with simvastatin and non-simvastatin agents. In this
      observational study, patients regularly using statins or aspirin had a lower
      incidence of EAC. Statins may have clinically useful effects in preventing the
      development of EAC. 

PMID- 22989237
TI  - Bodies and occlusion: item types, cognitive processes, and gender differences in
      mental rotation.
AB  - The aim of the current study was to reexamine previous findings in which the
      magnitude of the male advantage in mental rotation abilities increased when
      participants mentally rotated occluded versus nonoccluded items and decreased
      when participants mentally rotated human figures versus blocks. Mainly, the study
      aimed to address methodological issues noted on previous human figure mental
      rotations tests as the items composed of blocks and human body were probably not
      equivalent in terms of their cognitive requirements. Our results did not support
      previous research on embodied cognition as mental rotation performance decreased
      among both men and women when mentally rotating human figures compared to block
      items. However, for women, the effect of occlusion was decreased when mentally
      rotating human figures. Results are discussed in terms of task difficulty and
      gender differences in confidence and guessing behaviour.

PMID- 22989238
TI  - Early diagnosis and treatment of necrotizing fasciitis can improve survival: an
      observational intensive care unit cohort study.
AB  - BACKGROUND: The aim of this study was to describe the clinical characteristics,
      causative pathogens, clinical management and outcomes of patients presenting to a
      tertiary adult Australian intensive care unit (ICU) with a diagnosis of
      necrotizing fasciitis (NF). METHODS: This retrospective observational study was
      conducted in a 19-bed, level III, adult ICU in a 450-bed tertiary, regional
      hospital. Clinical databases were accessed for patients diagnosed with NF and
      admitted to The Geelong Hospital ICU between 1 February 2000 and 1 June 2011.
      Information on severity of sepsis, surgical procedures and microbiological
      results were collected. RESULTS: Twenty patients with NF were identified. The
      median age was 52.5 years and 38% were female. The overall mortality rate was
      8.3%. Common co-morbidities were diabetes (21%) and heart failure (17%), although
      50% of patients had no co-morbidities. Group A Streptococcus was the identified
      pathogen in 11 (46%) patients, and Streptococcus milleri group in 5 (21%)
      patients. Hyperbaric oxygen therapy was not used in the majority of patients. The
      initial antibiotics administered were active against subsequently cultured
      bacteria in 83% of patients. Median time to surgical debridement was 20 h.
      Diagnosis and management was delayed in the nosocomial group. CONCLUSIONS: This
      study reports physiological data, aetiology and therapeutic interventions in NF
      for an adult tertiary hospital. We demonstrate one of the lowest reported
      mortality rates, with early surgical debridement being achieved in the majority
      of patients. The main delay was found to be in the diagnosis of NF.

PMID- 22989239
TI  - A plea to university researchers.

PMID- 22989241
TI  - Childhood betrayal trauma and self-blame appraisals among survivors of intimate
      partner abuse.
AB  - Child abuse perpetrated by a close other, such as a parent, is linked to a wide
      range of detrimental effects, including an increased risk of self-blame. The
      current study evaluated whether experiences of childhood betrayal trauma were
      linked to self-blame following victimization in adulthood. A diverse sample of
      women (n = 230) from an urban city were recruited based on having experienced an
      incident of intimate partner abuse (IPA) reported to the local police. Women
      reported on their trauma histories and levels of self-blame for the target IPA
      incident. Results showed that a history of childhood betrayal trauma exposure
      predicted the degree of self-blame for the IPA incident. Women who experienced
      severe IPA during the target incident also indicated higher levels of self-blame.
      Findings from this study suggest that it may be important to target self-blame
      appraisals in interventions with adults exposed to abuse in childhood.

PMID- 22989240
TI  - Peritraumatic dissociation and peritraumatic emotional predictors of PTSD in
      Latino youth: results from the Hispanic family study.
AB  - This is the 1st study to examine peritraumatic dissociation and peritraumatic
      emotions as they predict symptoms and diagnosis of posttraumatic stress disorder
      (PTSD) in Latino youth. Our aim was to test the hypothesis that the degree of
      peritraumatic dissociation would predict the number of PTSD symptoms and PTSD
      clinical diagnosis when the influences of other salient factors were
      statistically controlled. We also explored the possible contributions of
      peritraumatic emotional responses to PTSD symptomatology and PTSD diagnosis. We
      expected that peritraumatic dissociation would emerge as a significant predictor
      of PTSD. A total of 204 Latino youth (mean age = 12.37 years) completed
      semistructured individual clinical interviews with bilingual research assistants.
      These interviews assessed trauma exposure, peritraumatic responses, and current
      psychopathology. A linear regression analysis demonstrated significant
      relationships between lifetime number of traumatic events, peritraumatic
      dissociation, shame, and number of PTSD symptoms endorsed. Significant inverse
      (protective) relationships were demonstrated between anger and guilt and current
      PTSD symptomatology. Logistic regression analysis demonstrated significant
      relationships between peritraumatic dissociation, shame, lifetime number of
      traumatic events experienced, and PTSD diagnosis. The analyses examined both the
      number of PTSD symptoms as well as diagnosis of PTSD while simultaneously
      controlling for age, lifetime exposure to traumatic events, time residing in the
      United States, and gender. These results support an increasingly robust body of
      empirical literature suggesting that the peritraumatic dissociative and emotional
      responses to trauma are important predictors of future PTSD diagnosis. Possible
      cultural factors contributing to the dissociative responses in Latino youth and
      clinical implications are discussed.

PMID- 22989242
TI  - Construct validity of three depersonalization measures in trauma-exposed college
      students.
AB  - Depersonalization is a type of dissociation characterized by feelings of
      unreality and detachment from one's sense of self. Despite a history rich in
      clinical description, the construct of depersonalization has proven difficult to
      define and measure. Available measures vary substantially in content, and all
      have relatively limited psychometric support. In this study the content validity,
      internal consistency, and convergent and discriminant validity of 3
      depersonalization measures were compared in a sample of 209 trauma-exposed
      college students. Measures were the Dissociative Experiences Scale ( E. M.
      Bernstein & F. W. Putnam, 1986 ), Cambridge Depersonalization Scale (CDS;  M.
      Sierra & G. E. Berrios, 2000 ), and Multiscale Dissociation Inventory (MDI;  J.
      Briere, 2002 ). All 3 measures exhibited adequate to high internal consistency
      for the depersonalization-derealization items. Based on  D. Westen and R.
      Rosenthal's (2003)  procedure for quantifying construct validity, the CDS and MDI
      demonstrated the best fit with the predicted pattern of correlations with
      measures of other constructs. The CDS and MDI also demonstrated the strongest
      evidence of content validity. Overall, the results most strongly support the use
      of the CDS and MDI for assessing depersonalization in this population.

PMID- 22989243
TI  - Dissociative and psychotic experiences of adolescents admitted to a psychiatric
      inpatient unit.
AB  - A positive correlation between the incidences of dissociative and psychotic
      experiences has been consistently reported in a variety of adult populations. The
      present study was a preliminary investigation of the association between
      dissociative and psychotic experiences in adolescents requiring inpatient mental
      health care. No previous research has investigated this relationship in an
      adolescent cohort. Adolescents currently under inpatient care (n = 18) completed
      questionnaires assessing their experience of dissociative and psychotic
      phenomena. In line with previous research, a significant positive correlation was
      found between dissociative and psychotic experiences that remained highly
      significant once similarities between measures were taken into account.
      Recognizing the relationship between psychotic and dissociative experiences may
      be important in developing appropriate and effective treatment for young people
      experiencing mental health difficulties. Although the study is cross-sectional in
      nature and has a small sample, the results offer further evidence of the robust
      relationship between dissociative and psychotic experiences.

PMID- 22989244
TI  - Posthypnotic state changes and flashbacks: analogous processes?
AB  - Careful study of the posttraumatic stress disorder and hypnosis literatures
      reveals some parallels between posttraumatic flashbacks and responses to
      posthypnotic suggestions. Highly susceptible subjects can slip into hypnosis
      spontaneously and accept and respond to implied or inadvertent suggestions, some
      of which may operate in a manner equivalent to posthypnotic suggestions. Later,
      exposure to appropriate cues may trigger an intrusive revivification of the
      hypnotic state in which the suggestion occurred. This sequence of events closely
      resembles the sequence of reactions that some individuals have to trauma that
      ultimately leads to flashbacks. Thus, flashbacks may be conceived of as intrusive
      posttraumatic revivifications of trauma-induced hypnosis-like states that are
      reactivated by trauma-reminiscent cues operating similarly to posthypnotic
      signals. Implications of viewing flashbacks in this way, especially if this view
      is supported by future research, could include significant changes in how
      posttraumatic stress disorder is conceptualized and treated.

PMID- 22989245
TI  - An exploration of young adults' progress in treatment for dissociative disorder.
AB  - Although treatment outcome research on dissociative disorders (DD) is increasing,
      an examination of treatment progress in young adults with these disorders remains
      noticeably absent from the literature. Many studies of DD patients report mean
      ages over 35. The present study examined the response to treatment of a subsample
      of young adults ages 18-30 with dissociative identity disorder and dissociative
      disorder not otherwise specified who participated in a naturalistic, longitudinal
      study of DD treatment outcome. Over 30 months, these patients demonstrated
      decreases in destructive behaviors and symptomatology as well as improved
      adaptive capacities. Compared to the older adult participants in the study, the
      young adults were more impaired initially. However, these younger patients
      improved at a rapid pace, such that their clinical presentations were similar to
      or more improved than those of the older adults at the 30-month follow-up. This
      brief report suggests not only that young adult DD patients can benefit from a
      trauma-focused, phasic treatment approach but that their treatment may progress
      at a faster pace than that of older adults with DD.

PMID- 22989250
TI  - Single-incision laparoscopic adrenalectomy at Viet Duc University Hospital.
AB  - INTRODUCTION: Laparoscopic adrenalectomy is the technique of choice in the
      treatment of adrenal tumors. SILS has recently been introduced in this field and
      applied in Viet Duc University Hospital. Herein, we report our experience with
      single-incision transperitoneal adrenalectomy. METHODS: Between August 2010 and
      January 2012, 61 patients (23 men, 38 women) underwent SILS adrenalectomy at our
      institution. The diagnoses consisted of 20 patients with pheochromocytoma, 17
      with nonfunctioning adenoma, 16 with Conn syndrome, 4 with Cushing syndrome and 4
      with adrenal cysts. The mean age was 47.8 years (range, 21-68 years). There were
      29 right-sided and 32 left-sided tumors; their mean diameter was 30.7 mm (range,
      8-59 mm). Patients were in the flank position with the operated side up. A 2.5-cm
      pararectal incision at the level of the umbilicus was made to insert the SILS
      Port. RESULTS: The mean operating time was 78 min (range, 50-120 min), and mean
      blood loss was approximately 70 mL. Left-sided tumors were excised entirely with
      the SILS technique. Right-sided lesions sometimes required an additional trocar
      (hybrid technique). No drainage was needed at the operating site. There were no
      intraoperative or postoperative complications, but one case was converted to the
      conventional three-port technique. The mean length of hospital stay was 3.4 days
      (range, 2-6 days). CONCLUSION: Our preliminary results show that SILS
      adrenalectomy is safe and technically feasible. It should be considered among the
      surgical managements for selected patients with adrenal tumors.

PMID- 22989251
TI  - Quantitative determination of the band gap of WS2 with ambipolar ionic liquid
      gated transistors.
AB  - We realized ambipolar field-effect transistors by coupling exfoliated thin flakes
      of tungsten disulfide (WS(2)) with an ionic liquid dielectric. The devices show
      ideal electrical characteristics, including very steep subthreshold slopes for
      both electrons and holes and extremely low OFF-state currents. Thanks to these
      ideal characteristics, we determine with high precision the size of the band gap
      of WS(2) directly from the gate-voltage dependence of the source-drain current.
      Our results demonstrate how a careful use of ionic liquid dielectrics offers a
      powerful strategy to study quantitatively the electronic properties of nanoscale
      materials.

PMID- 22989252
TI  - Does preparedness planning improve attitudes and completion of advance directives
      in patients with symptomatic heart failure?
AB  - BACKGROUND AND OBJECTIVE: There is little evidence to support whether
      interventions that engage patients with symptomatic heart failure (HF) in
      preparedness planning impacts completion of advance directives (ADs). This study
      was conducted to assess the impact of a palliative care intervention on health
      perceptions, attitudes, receipt of information and knowledge of ADs, discussion
      of ADs with family and physicians, and completion of ADs in a cohort of patients
      with symptomatic HF. METHODS: Thirty-six patients hospitalized for HF
      decompensation were recruited and referred for an outpatient consultation with a
      palliative care specialist in conjunction with their routine HF follow-up visit
      after discharge; telephone interviews to assess health status and attitudes
      toward ADs were conducted before and 3 months after the initial consultation
      using an adapted version of the Advance Directive Attitude Survey (ADAS).
      Information pertaining to medical history and ADs was verified through medical
      chart abstraction. RESULTS AND CONCLUSION: The current study found support for
      enhancing attitudes and completion of ADs following a palliative care
      consultation in patients with symptomatic HF. Despite a significant increase in
      attitudes toward completion of ADs following the intervention, only 47% of the
      participants completed ADs. This finding suggests that although education and
      understanding of ADs is important and can result in more positive attitudes, it
      does not translate to completion of ADs in all patients.

PMID- 22989253
TI  - Tandem aza-Wittig/carbodiimide-mediated annulation applicable to 1,2-diaza-1,3
      dienes for the one-pot synthesis of fully substituted 1,2-diaminoimidazoles.
AB  - One-pot sequential aza-Michael, Staudinger, and aza-Wittig reactions on 1,2-diaza
      1,2-dienes (DDs) can afford fully substituted 1,2-diaminoimidazoles. A plausible
      mechanism for the imidazole core formation involving an intramolecular ring
      closure of the carbodiimide-derived phosphazene intermediate is given. The
      reported strategy has sufficient flexibility to allow substituted 1,2
      diaminoimidazoles with orthogonal nitrogen-protective groups to be generated from
      a variety of heterocumulene moieties linked to the DDs skeleton.

PMID- 22989254
TI  - Causes and trends in traumatic brain injury for United States adolescents.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability among
      United States adolescents. The authors sought to determine causes and trends for
      TBI-related hospitalizations in the United States adolescent population (10-19
      years). The authors identified common causes and trends of adolescent TBI,
      overall and within 2-year age categories, using hospitalization data from 2005 to
      2009 in the Nationwide Inpatient Sample. The leading cause of adolescent TBI
      overall was motor vehicle occupant accidents (35%), which are also the leading
      cause in the 14-15, 16-17, and 18-19 year age groups. Falls were the cause of
      most TBI in the 10-11 year (23%) and 12-13 year (20%) age groups. For both
      unintentional and intentional mechanisms of injury, there was evidence of
      increasing hospitalizations with increasing age. From 2005 to 2009, the overall
      annual incidence of adolescent TBI hospitalizations decreased 21% from an
      estimated 75.5-59.3 per 100,000 (p<0.001). These rates declined for mild,
      moderate, and severe TBI, and decreased for 2-year age groups, except for the 18
      19 year-old group. For TBI attributable to motor vehicle occupants, rates
      declined 27% from 27.6 to 20.2 per 100,000 (p<0.001). Motor vehicle occupant
      injuries account for 42% of in-hospital mortality from adolescent TBI; however,
      firearms are the most lethal mechanism with 46% proportional mortality among
      victims of firearm-related TBI. Rates of adolescent TBI-related hospitalizations
      have decreased overall. Motor vehicle accidents and firearms were identified as
      leading causes of injury and mortality for adolescent TBI, and represent
      potential targets for intervention.

PMID- 22989255
TI  - Sonographic cervical motion tenderness: A sign found in a patientA with pelvic
      inflammatory disease.
AB  - No single historical, physical, laboratory, or imaging finding is both sensitive
      and specific for the diagnosis of pelvic inflammatory disease (PID). Cervical
      motion tenderness (CMT), when present, is classically found on bimanual
      examination of the cervix and uterus. CMT is often associated with PID but can be
      present in other disease entities. We present a case report of a patient who was
      ultimately diagnosed with acute PID. The evaluating physician performed a trans
      vaginal bedside ultrasound, and the operator appreciated 'sonographic CMT'. In
      cases where the physical examination is equivocal or in patients where the exact
      location of tenderness is difficult to discern, performing a trans-vaginal
      bedside ultrasound examination can increase the physician's confidence that CMT
      is present as the cervix is being directly visualized as pressure is applied with
      the probe. Bedside ultrasound and specifically sonographic CMT may prove useful
      in diagnosing PID in patients with equivocal or unclear physical examination
      findings.

PMID- 22989256
TI  - Caregivers' anxiety and self-efficacy in palliative care.
AB  - This study examined the relationship between caregivers' anxiety supporting a
      patient with advanced cancer and self-efficacy and their socio-demographic
      characteristics, and then whether these variables could influence their self
      efficacy. One hundred and seven caregivers of advanced cancer patients
      participated in the study and completed the Greek versions of the State-Trait
      Anxiety Inventory (STAI) and the General Perceived Self-efficacy Scale (GSE).
      Significant comparisons were found between State anxiety and female gender (P=
      0.009), cohabitation (P= 0.002) and relationship with the patient (P= 0.004);
      statistically significant associations were found between State, Trait anxiety
      and self-efficacy scores of caregivers (P < 0.0005 respectively). A multiple
      regression model (enter method) showed women (P= 0.005), spouses (P= 0.01) and
      self-efficacy (P= 0.02) as the significant predictors of State anxiety.
      Furthermore, self-efficacy seemed to be the strongest contributor of trait
      anxiety (P < 0.0005). Female caregivers and spouses of advanced cancer patients
      experience more state anxiety levels than men and other caregivers respectively.
      In addition, caregivers with low self-efficacy are more likely to have elevated
      anxiety scores than self-efficacious caregivers. These findings can help
      healthcare professionals focus on some problems common to caregivers of cancer
      patients and plan appropriate interventions.

PMID- 22989257
TI  - Recognizing nucleosides with transverse electronic transport via perpendicular
      direction of base planes for DNA sequencing.
AB  - Putting the four DNA nucleosides in the middle of gold [111] nanoelectrodes with
      base planes parallel to the electrode surface layer, we study the transverse
      electronic transport properties of four nucleosides along the direction of
      electrodes. First, the optimal distance of the electrodes is released. The
      results show that the optimal electrode distance to study transverse electronic
      transport characteristics of DNA nucleosides is about 0.68 nm. Second, we
      theoretically calculate the conductance and current of the four nucleosides via
      perpendicular direction of base planes in the bias range of [-2, 2] V by
      exploiting the first principle theory. According to the calculated results, we
      propose three methods to recognize the nucleoside type in practice application.

PMID- 22989258
TI  - Editorial Comment to extracorporeal shock wave lithotripsy for distal ureteral
      calculi: Improved efficacy using low frequency.

PMID- 22989259
TI  - Molecular characterization and clinical presentation of HKalphaalpha and anti
      HKalphaalpha alleles in southern Chinese subjects.
AB  - The HKalphaalpha allele is a rearrangement occurring in the alpha-globin gene
      cluster containing both the -alpha(3.7) and alphaalphaalpha(anti4.2) unequal
      crossover junctions. The anti-HKalphaalpha allele is the reciprocal product
      containing both the -alpha(4.2) and alphaalphaalpha(anti3.7) unequal crossover
      junctions, which had been predicted but had not been detected previously. The
      phenotypic feature and population frequency of these two unusual alleles were not
      described. We report the identification of nine individuals carrying the
      HKalphaalpha allele and two individuals carrying the anti-HKalphaalpha allele in
      southern China and describe their phenotype and haplotype data. The molecular
      structures of HKalphaalpha allele and anti-HKalphaalpha allele were confirmed by
      two-round nested polymerase chain reaction assay. The mechanism of origin of both
      alleles is related to probably simultaneous double crossover. Heterozygotes of
      HKalphaalpha or anti-HKalphaalpha allele show a normal hematological phenotype.
      Finally, we report the carrier rates of these both alleles in the Guangxi Zhuang
      Autonomous Region of southern China, namely, ~0.07% for the HKalphaalpha allele
      and ~0.02% for the anti-HKalphaalpha allele.

PMID- 22989260
TI  - Theoretical effect of hyperventilation on speed of recovery and risk of
      rehypnotization following recovery - a GasMan(r) simulation.
AB  - BACKGROUND: Hyperventilation may be used to hasten recovery from general
      anesthesia with potent inhaled anesthetics. However, its effect may be less
      pronounced with the newer, less soluble agents, and it may result in
      rehypnotization if subsequent hypoventilation occurs because more residual
      anesthetic will be available in the body for redistribution to the central
      nervous system. We used GasMan(r) simulations to examine these issues. METHODS:
      One MAC of isoflurane, sevoflurane, or desflurane was administered to a
      fictitious 70 kg patient for 8 h with normoventilation (alveolar minute
      ventilation [VA] 5 L.min-1), resulting in full saturation of the vessel rich
      group (VRG) and >95% saturation of the muscle group. After 8 h, agent
      administration was stopped, and fresh gas flow was increased to 10 L.min-1 to
      avoid rebreathing. At that same time, we continued with one simulation where
      normoventilation was maintained, while in a second simulation hyperventilation
      was instituted (10 L.min-1). We determined the time needed for the partial
      pressure in the VRG (FVRG; representing the central nervous system) to reach 0.3
      MAC (MACawake). After reaching MACawake in the VRG, several degrees of
      hypoventilation were instituted (VA of 2.5, 1.5, 1, and 0.5 L.min-1) to determine
      whether FVRG would increase above 0.3 MAC(= rehypnotization). RESULTS: Time to
      reach 0.3 MAC in the VRG with normoventilation was 14 min 42 s with isoflurane, 9
      min 12 s with sevoflurane, and 6 min 12 s with desflurane. Hyperventilation
      reduced these recovery times by 30, 18, and 13% for isoflurane, sevoflurane, and
      desflurane, respectively. Rehypnotization was observed with VA of 0.5 L.min-1
      with desflurane, 0.5 and 1 L.min-1 with sevoflurane, and 0.5, 1, 1.5, and 2.5
      L.min-1 with isoflurane. Only with isoflurane did initial hyperventilation
      slightly increase the risk of rehypnotization. CONCLUSIONS: These GasMan(r)
      simulations confirm that the use of hyperventilation to hasten recovery is
      marginally beneficial with the newer, less soluble agents. In addition,
      subsequent hypoventilation results in rehypnotization only with more soluble
      agents, unless hypoventilation is severe. Also, initial hyperventilation does not
      increase the risk of rehypnotization with less soluble agents when subsequent
      hypoventilation occurs. Well-controlled clinical studies are required to validate
      these simulations.

PMID- 22989261
TI  - Radiotherapy for inoperable and refractory endometriosis presenting with massive
      hemorrhage: a case report.
AB  - INTRODUCTION: Many patients with endometriosis are treated with medication or by
      surgical approaches. However, a small number of patients do not respond to
      medication and are inoperable because of comorbidities. This case report shows
      the effectiveness of radiotherapy for refractory endometriosis and includes a
      time series of serum estradiol levels. CASE PRESENTATION: A 47-year-old Asian
      woman presented to our facility with uncontrolled endometriosis refractory to
      medication. Our patient was considered inoperable because of severe idiopathic
      thrombocytopenic purpura, and underwent radiotherapy for massive genital bleeding
      requiring blood transfusions. A radiation dose of 20Gy in 10 fractions was
      delivered to the pelvis, including the bilateral ovaries, uterus, and myomas. An
      additional 10Gy in five fractions was delivered to the endometrium to control
      residual bleeding. Genital bleeding was completely inhibited on day 46 after
      radiotherapy. Hormonal analysis revealed that radiotherapy induced post
      menopausal status. Two years after radiotherapy, atypical genital bleeding had
      not recurred and has been well controlled without side effects. CONCLUSIONS:
      Disrupted ovarian function is an adverse effect of radiotherapy. However,
      radiotherapy can be useful for inducing menopause. In cases of medication
      refractory or inoperable endometriosis, radiotherapy would be an effective
      treatment option.

PMID- 22989262
TI  - Association of TAP1 and TAP2 polymorphisms with the outcome of persistent HBV
      infection in a northeast Han Chinese population.
AB  - OBJECTIVE: Transporter associated with antigen processing (TAP) plays a central
      role in a cellular immune response against HBV. Polymorphisms exist at the coding
      region of TAP and alter its structure and function. The aim of this study was to
      evaluate the potential relationship between polymorphisms of TAP and different
      outcomes of persistent HBV infection in a Han population in northeastern China.
      MATERIAL AND METHODS: 189 HBV spontaneously recovered (SR) subjects, 571 HBV
      infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis
      (LC) and 195 hepatocellular carcinoma (HCC) individuals were included in this
      study. TAP1-333 Ile/Val and -637 Asp/Gly, TAP2-651 Arg/Cys and -687 Stop/Gln were
      genotyped in all the samples by using a PCR-RFLP method. RESULTS: The frequency
      of TAP1-637-Gly (allele G) was significantly higher in persistently HBV-infected
      individuals (CHB and LC) than that of SR subjects (OR = 1.58, 95% CI 1.12-2.45, p
      = 0.024; OR = 1.78, 95% CI 1.27-2.68, p = 0.002) by a logistic regression
      analysis. In addition, the statistically significant difference in the
      distribution of TAP2-651-Cys (allele T) was observed between HCC cases and SR
      controls (OR = 2.30, 95% CI 1.51-3.72, p < 0.001), and TAP2-687-Gln (allele C) in
      CHB patients was more common than that in SR subjects (OR = 1.41, 95% CI 1.13
      1.97, p = 0.021). The data also revealed that haplotype 687 Gln-651 Cys-637 Gly
      333 Ile was strongly associated with persistent HBV infection (CHB, LC and HCC)
      (p < 0.001, < 0.05 and < 0.001, respectively). CONCLUSION: These results
      suggested that TAP variants were likely to play a substantial role in different
      outcomes of persistent HBV infection in the studied population.

PMID- 22989263
TI  - Fluorescence quenching by intercalation of a pyrene group tethered to an N4
      modified cytosine in duplex DNA.
AB  - A series of duplex DNA oligomers was prepared that contain a pyrene chromophore
      linked by a trimethylene chain (-(CH2 )3 -) to N(4) of a cytosine. The pyrene
      group stabilizes the DNA as evidenced by an increase in melting temperature. The
      absorption spectrum of the linked pyrene chromophore shows a temperature
      dependent shift and there is also a strong induced circular dichroism spectrum
      attributed to the pyrene group. The fluorescence of the pyrene chromophore is
      strongly quenched at room temperature by linkage to the DNA, but it increases
      above the melting temperature. We attribute these observations to intramolecular
      intercalation of the pyrene group at a base pair adjacent to its linkage site at
      cytosine.

PMID- 22989264
TI  - Combination of fluvastatin with pegylated interferon/ribavirin therapy reduces
      viral relapse in chronic hepatitis C infected with HCV genotype 1b.
AB  - BACKGROUND AND AIM: Although the anti-hepatitis C virus (HCV) effect of statins
      in vitro and clinical efficacy of fluvastatin combined with Pegylated interferon
      (PEG-IFN)/ribavirin therapy for chronic hepatitis C (CHC) have been reported, the
      details of clinical presentation are largely unknown. We focused on viral relapse
      that influences treatment outcome, and performed a post-hoc analysis by using
      data from a randomized controlled trial. METHODS: Thirty-four patients in the
      fluvastatin group and 33 patients in the non-fluvastatin group who achieved
      virological response (complete early virological response [cEVR] or late
      virological response [LVR]) with PEG-IFN/ribavirin therapy were subjected to this
      analysis. Factors contributing to viral relapse were identified by using multiple
      logistic regression analysis. RESULTS: Relapse rate in patients with cEVR was
      significantly lower in the fluvastatin group (2 of 23, 8.7%) than in the non
      fluvastatin group (9 of 26, 34.6%; P = 0.042). The use of fluvastatin decreased
      relapse rate in patients with LVR (27.3% vs 57.1%), though not significantly.
      Overall, relapse rate was significantly lower in the fluvastatin group (14.7%; 5
      of 34) than in the non-fluvastatin group (39.4%; 13 of 33; P = 0.027).
      Multivariate analysis identified absence of fluvastatin (P = 0.027, odds ratio
      [OR] = 3.98, 95% confidence interval [CI] = 1.05-15.11) and low total ribavirin
      dose (P = 0.002, OR = 2.41, 95% CI = 1.38-4.19) as independent factors
      contributing to relapse. CONCLUSION: The concomitant addition of fluvastatin
      significantly suppressed viral relapse, resulting in the improvement of sustained
      virological response rate, in PEG-IFN/ribavirin therapy for CHC patients with HCV
      genotype 1b and high viral load.

PMID- 22989265
TI  - Stature is an essential predictor of muscle strength in children.
AB  - BACKGROUND: Children with growth retardation or short stature generally present
      with lower strength than children of the same chronological age. The aim of the
      study was to establish if strength was dependent on variables related to stature
      in a population of healthy children and to propose practical predictive models
      for the muscle functions tested. A secondary aim was to test for any learning
      effects concerning strength measured at two successive visits by children.
      METHODS: Hand grip, elbow flexion and extension, and knee flexion and extension
      were measured by fixed dynamometry in 96 healthy subjects (47 girls and 49 boys,
      aged from 5 to 17 years). RESULTS: For the present paediatric population, muscle
      strength was highly dependent on height. Predictive models are proposed for the
      muscle functions tested. No learning effect between the first and the second
      visit was detected for any of the muscle functions tested. CONCLUSIONS: This work
      shows that strength measurements using fixed dynamometry are reliable in children
      when using appropriate standardization of operating procedures. It underlines the
      particular relationship between body stature and muscle strength. Predictive
      equations may help with assessing the neuromuscular involvement in children
      suffering from various disorders, particularly those affecting their stature.

PMID- 22989266
TI  - Illness trajectory and Internet as a health information and communication channel
      used by parents of infants admitted to a neonatal intensive care unit.
AB  - BACKGROUND: Internet use became an integral part of the healthcare relationship.
      Literature indicates that the illness trajectory plays a role in the use of
      Internet as a health information tool. This study focuses on infants admitted to
      a neonatal intensive care unit. AIM: This study aims to understand how the
      illness trajectory triggers the use of Internet by parents of infants admitted to
      a neonatal intensive care unit, using a conceptual framework influenced by Corbin
      and Strauss' illness trajectory. DESIGN: This study was based on a qualitative
      longitudinal multiple-case study design. METHODS: From July 2007-August 2008 and
      from June 2009-May 2010, parents with newborns were prospectively interviewed
      over a period of 10 months. Parents were recruited in four neonatal intensive
      care units. The interviews were subject of a thematic content analysis. RESULTS:
      The multi-layered illness trajectory triggers Internet use. Parents' online
      health information behaviour interacts with other information channels too (such
      as interaction with healthcare professionals). Parents accumulate knowledge along
      the illness trajectory affecting their information needs. The sickness trajectory
      helps to understand the complexity of the information behaviour. Labels have a
      major impact on the effectiveness of search strategies. CONCLUSIONS: Nursing and
      other healthcare professionals should become more aware about the complex
      relationship between information needs and Internet use along the illness
      trajectory of an infant. As such, they will be more able to assist parents in
      finding and evaluating high-quality online information at the right time.

PMID- 22989267
TI  - Loss of masculine identity, marital affection, and sexual bother in men with
      localized prostate cancer.
AB  - INTRODUCTION: Erectile dysfunction (ED) is one of the most frequent sources of
      distress after treatment for prostate cancer (PCa), yet evidence suggests that
      men do not easily adjust to loss of sexual function over time. A hypothesized
      determinant of men's adaptation to ED is the degree to which they experience a
      loss of masculine identity in the aftermath of PCa treatment. AIMS: The aims of
      this study were (i) to describe the prevalence of concerns related to diminished
      masculinity among men treated for localized PCa; (ii) to determine whether
      diminished masculinity is associated with sexual bother, after controlling for
      sexual functioning status; and (iii) to determine whether men's marital quality
      moderates the association between diminished masculinity and sexual bother.
      METHODS: We analyzed cross-sectional data provided by 75 men with localized PCa
      who were treated at one of two cancer centers. Data for this study were provided
      at a baseline assessment as part of their enrollment in a pilot trial of a couple
      based intervention. MAIN OUTCOME MEASURES: The sexual bother subscale from the
      Prostate Health-Related Quality-of-Life Questionnaire and the Masculine Self
      Esteem and Marital Affection subscales from Clark et al's PCa-related quality-of
      life scale. RESULTS: Approximately one-third of men felt they had lost a
      dimension of their masculinity following treatment. Diminished masculinity was
      the only significant, independent predictor of sexual bother, even after
      accounting for sexual functioning status. The association between diminished
      masculinity and sexual bother was strongest for men whose spouses perceived low
      marital affection. CONCLUSIONS: Diminished masculinity is a prominent, yet
      understudied concern for PCa survivors. Regardless of functional status, men who
      perceive a loss of masculinity following treatment may be more likely to be
      distressed by their ED. Furthermore, its impact on adjustment in survivorship may
      rely on the quality of their intimate relationships.

PMID- 22989268
TI  - Pyramidalization of the glycosidic nitrogen provides the way for efficient
      cleavage of the N-glycosidic bond of 8-OxoG with the hOGG1 DNA repair protein.
AB  - A mechanistic pathway for cleavage of the N-glycosidic bond of 8-oxo-2'
      deoxyguanosine (oxoG) catalyzed with the human 8-oxoguanine glycosylase 1 DNA
      repair protein (hOGG1) is proposed in this theoretical study. The reaction scheme
      suggests direct proton addition to the glycosidic nitrogen N9 of oxoG from the
      Nepsilon-ammonium of Lys249 residue of hOGG1 that is enabled owing to the N9
      pyramidal geometry. The N9-pyramidalization of oxoG is induced within hOGG1
      active site. The coordination of N9 nitrogen to the Nepsilon-ammonium of Lys249
      unveiled by available crystal structures enables concerted, synchronous
      substitution of the N9-C1' bond by the N9-H bond. The reaction is compared with
      other pathways already proposed by means of calculated activation energies. The
      DeltaG(#) energy for the newly proposed reaction mechanism calculated with the
      B3LYP/6-31G(d,p) method 17.0 kcal mol(-1) is significantly lower than DeltaG(#)
      energies for other reactions employing attack of the Nepsilon-amino group to the
      anomeric carbon C1' of oxoG and attack of the Nepsilon-ammonium to the N3
      nitrogen of oxoG base. Moreover, activation energy for the oxoG cleavage
      proceeding via N9-pyramidalization is lower than energy calculated for normal G
      because the electronic state of the five-membered aromatic ring of oxoG is better
      suited for the reaction. The modification of aromatic character introduced by
      oxidation to the nucleobase thus seems to be the factor that is checked by hOGG1
      to achieve base-specific cleavage.

PMID- 22989269
TI  - The helix located between the two domains of a mip-like peptidyl-prolyl cis-trans
      isomerase is crucial for its structure, stability, and protein folding ability.
AB  - FKBP22, a PPIase (peptidyl-prolyl cis-trans isomerase) produced by Escherichia
      coli, binds FK506 and rapamycin (both immunosuppressive drugs), shares
      significant homology with the Mip-like virulence factors, and has been thought to
      carry a long alpha-helix (namely alpha3) between its two domains. To understand
      whether the length of helix alpha3 plays any role in the structure, function, and
      stability of FKBP22-like proteins, we studied a recombinant E. coli FKBP22
      (rFKBP22) and its four helix alpha3 mutant variants by various in vitro probes.
      Of the helix alpha3 mutants, two were deletion mutants (rFKBP22D5 and
      rFKBP22D30), whereas the two others were insertion mutants (rFKBP22I3 and
      rFKBP22I6). Our investigations revealed that the molecular dimensions,
      dimerization efficiencies, secondary structures, tertiary structures,
      stabilities, and protein folding abilities of all mutant proteins are different
      from those of rFKBP22. Conversely, the rapamycin binding affinities of the mutant
      proteins were affected very little. Urea-induced unfolding of each protein
      followed a two-state mechanism and was reversible in nature. Interestingly,
      rFKBP22D30 was the least stable, whereas rFKBP22I3 appeared to be the most stable
      of the five proteins. The data together suggest that length of helix alpha3
      contributes significantly to the preservation of the structure, function, and
      stability of E. coli FKBP22.

PMID- 22989270
TI  - Depression and posttraumatic stress disorder among HIV-infected Gambians on
      antiretroviral therapy.
AB  - Mood disorders are more frequent among people with HIV infection than among non
      HIV-infected individuals of the same age, socioeconomic status, and HIV risks.
      They have been associated with worse adherence and clinical outcomes, yet remain
      underdiagnosed and undertreated in sub-Saharan Africa. We explored the
      relationship between mood disorders using the 10-item depression scale of the
      Centers for Epidemiological Studies (CES-D10) and the 22-item Impact of Events
      Scale-Revised (IES-R) for posttraumatic stress disorder, and a range of
      demographic and HIV-related variables among 252 consecutive subjects on
      antiretroviral therapy (ART). The study was conducted in the Genito-Urinary
      Medicine Clinic of the Medical Research Council's Gambia Unit. These screening
      tests were positive in 7% and 30%, respectively, of the patients, with higher
      scores (more depression or more post-traumatic stress) associated with female
      gender, more advanced WHO clinical stage, and lower Karnofsky Perfomance Scale
      rating. Higher CES-D10 scores were also seen among those on their second ART
      regimen. No relationship was seen with age, time on ART, viral load, or CD4 cell
      count. Compared to an earlier study at the same site in subjects prior to
      starting ART, the prevalence of depression in those stabilized on ART was
      dramatically reduced (by 34%, from 41%) while that of PTSD dropped less (by 13%,
      from 43%). Integrating the CES-D10 or a similar instrument into patient
      preparation for ART is recommended in order to identify those who may benefit
      from further mental health investigations, specific therapy, or closer follow-up
      during early ART.

PMID- 22989271
TI  - HIV/sexual risk reduction interventions in China: a meta-analysis.
AB  - The current study was a meta-analysis of the efficacy of educational,
      psychosocial or behavioral interventions that were conducted in China to promote
      HIV/sexual risk reduction. A total of 26 intervention studies qualified for the
      meta-analysis. Outcome variables for which effect sizes were calculated included
      condom use with different types of sexual partners, HIV/AIDS knowledge, condom
      use knowledge, intentions of condom use, condom use self-efficacy, and others.
      Mean weighted effect sizes were calculated for each outcome measure across
      reviewed studies; effect size for each outcome measure was weighted by their
      inverse variance; fixed effects and random effects meta-analytic procedures were
      used. The Q statistic was used to examine whether the effect sizes were
      homogeneous in nature and moderating analysis (i.e., the Q(b) statistic) was used
      to compare the effect sizes of intervention studies that were different in a
      number of categorical variables. The reviewed interventions were successful in
      improving HIV knowledge (d=0.706), condom use knowledge (d=0.620), attitudes
      toward people living with HIV/AIDS (PLWHA; d=0.625) and in increasing condom use
      with regular partners (d=0.477), condom use with casual partners (d=0.444),
      general condom use (d=0.408), and condom use self-efficacy (d=0.584) among target
      audiences. In addition, moderating analyses on three most examined variables,
      including HIV knowledge, condom use, and attitudes toward PLWHA, demonstrated
      that interventions that reported the conduction of formative research and process
      evaluation, that were peer-led, and that included only one follow-up were more
      likely to report a positive impact on condom use behavior among target audiences
      (p<0.001), HIV knowledge (p<0.001), or attitudes toward PLWHA (p<0.001).

PMID- 22989272
TI  - Forming a flossing habit: an exploratory study of the psychological determinants
      of habit formation.
AB  - OBJECTIVES: Habit formation has been proposed as a means to promote maintenance
      of healthy behaviours, but there have been few investigations into how habits are
      formed. This exploratory study sought to model determinants of the formation of a
      dental flossing habit, including placement of the behaviour within the routine
      (before vs. after tooth-brushing), past behaviour, prospective memory ability,
      and motivational factors. DESIGN AND METHOD: All participants (N = 50) received a
      motivational intervention designed to initiate behaviour change and habit
      formation. Half of the participants were instructed to floss before brushing, and
      half after. Participants subsequently self-reported flossing behaviour daily and,
      4 weeks later, flossing automaticity. Automaticity and flossing frequency were
      also measured at 8-month follow-up. RESULTS: Participants with stronger
      prospective memory ability, higher levels of past behaviour, and a more positive
      attitude flossed more frequently during the study. Stronger automaticity was
      predicted by positive attitudes, and increased behaviour frequency during and
      prior to the study. Those who flossed after brushing (rather than before) tended
      to form stronger flossing habits and, at 8-month follow-up, had stronger habits
      and flossed more frequently. CONCLUSIONS: Habit forming interventions might
      usefully consider features of everyday routines and how behaviour may be
      reinforced. Suggestions for further research using more methodologically rigorous
      designs are offered. STATEMENT OF CONTRIBUTION: What is already known on this
      subject? The formation of habit - that is, a learnt automatic response to
      contextual cues - requires initiation of a behaviour and repetition in a constant
      context. A recent formation study showed variation in habit strength despite
      equal repetitions, indicating that factors other than repetition may be important
      in habit development. From studies of routine behaviour, the boundaries between
      sub-routines are characterized by different processes than the middle of sub
      routines, suggesting that placement of behaviour within existing routines may
      affect the likelihood of habit formation. What does this study add? Greater
      prospective memory ability predicted more frequent dental flossing. Initiating
      flossing after rather than before tooth-brushing promoted stronger habits.
      Positive attitudes impacted directly on habit formation, independent of behaviour
      repetition.

PMID- 22989273
TI  - A transition-state interaction shifts nucleobase ionization toward neutrality to
      facilitate small ribozyme catalysis.
AB  - One mechanism by which ribozymes can accelerate biological reactions is by
      adopting folds that favorably perturb nucleobase ionization. Herein we used Raman
      crystallography to directly measure pK(a) values for the Ade38 N1 imino group of
      a hairpin ribozyme in distinct conformational states. A transition-state analogue
      gave a pK(a) value of 6.27 +/- 0.05, which agrees strikingly well with values
      measured by pH-rate analyses. To identify the chemical attributes that contribute
      to the shifted pK(a), we determined crystal structures of hairpin ribozyme
      variants containing single-atom substitutions at the active site and measured
      their respective Ade38 N1 pK(a) values. This approach led to the identification
      of a single interaction in the transition-state conformation that elevates the
      base pK(a) > 0.8 log unit relative to the precatalytic state. The agreement of
      the microscopic and macroscopic pK(a) values and the accompanying structural
      analysis supports a mechanism in which Ade38 N1(H)+ functions as a general acid
      in phosphodiester bond cleavage. Overall the results quantify the contribution of
      a single electrostatic interaction to base ionization, which has broad relevance
      for understanding how RNA structure can control chemical reactivity.

PMID- 22989274
TI  - Identification of insulin-like growth factor 2 mRNA-binding protein 3 as a
      radioresistance factor in squamous esophageal cancer cells.
AB  - Identification of reliable markers of radiosensitivity and the key molecules that
      donate susceptibility to anticancer treatments to esophageal cancer cells would
      be highly desirable. We found that the mRNA expression of insulin-like growth
      factor 2 mRNA-binding protein 3 (IGF2BP3) was higher in radioresistant TE-5 and
      TE-9 cells than in radiosensitive TE-12 cloneA1 cells. Conversely, knocking down
      expression of IGF2BP3 mRNA in TE-5 and TE-9 cells using small interfering RNA
      significantly enhanced their radiosensitivity. Furthermore, patients with
      squamous cell esophageal cancers strongly expressing IGF2BP3 tended to respond
      poorly to chemoradiation. These data suggest that IGF2BP3 may be a key marker of
      radiosensitivity that diminishes the susceptibility of squamous cell esophageal
      cancer cells to radiotherapy. IGF2BP3 may, thus, be a useful target for improving
      radiotherapy for patients with esophageal squamous cell carcinoma. 

PMID- 22989275
TI  - Results of a statewide survey of adolescent substance use screening rates and
      practices in primary care.
AB  - Professional guidelines recommend annual screening, brief intervention, and
      referral to treatment (SBIRT) as part of health maintenance for all adolescents,
      but reported screening rates have been low and no report has documented the
      techniques being used. The objective of this study was to describe the results of
      a statewide questionnaire regarding adolescent substance use screening rates and
      techniques used by primary care physicians practicing in Massachusetts. A
      questionnaire was mailed to every licensed physician registered as practicing
      pediatrics (N = 2176), family medicine (N = 1335), or both (N = 8) in the
      Massachusetts Board of Medicine database. After eliminating physicians who did
      not provide care for adolescents, the survey response rate was 28% and the final
      analyzable sample consisted of 743 surveys. Less than half of respondents
      reported using a validated adolescent screening tool. The majority of respondents
      used ineffective screening practices for adolescent substance use. Further
      physician training is recommended to encourage the use of developmentally
      appropriate screening tools and interventions for adolescents.

PMID- 22989276
TI  - Secular trends in prevalence of alcohol use disorder and its correlates in Korean
      adults: results from Korea National Health and Nutrition Examination Survey 2005
      and 2009.
AB  - The Alcohol Use Disorders Identification Test (AUDIT) has been found to provide
      an accurate measure for risk of hazardous and harmful alcohol use, as well as
      possible dependence. Data from 2 representative samples of 7693 adults in the
      Korea National Health and Nutrition Examination Survey (KNHANES) 2005 and 6276
      participants in 2009 were analyzed. The overall age-adjusted prevalence of
      alcohol use disorder (AUD) in 2009 (38.8%) was higher than that in 2005 (32.7%),
      with a difference of 6.1% (95% confidence interval [CI], 2.9%-9.3%; P = .0002).
      Men were about 7 times as likely as women to meet the criteria for AUD (odds
      ratio [OR] = 7.16; 95% CI, 6.27-8.17). Current smoking was the most important
      correlate associated with AUD in both genders (women: OR = 6.03; 95% CI, 4.40
      8.27; men: OR = 2.83; 95% CI, 2.29-3.48). Among women, unmarried (OR = 1.76; 95%
      CI, 1.35-2.31), less than high school education (OR = 2.71, 95% CI, 1.86-3.96),
      and lowest income (OR = 1.45, 95% CI, 1.06-1.97) were associated with AUD. These
      findings provide the most updated prevalence estimates of AUD in the Korean
      population and they highlight its strong association with smoking, gender
      differences, and lower socioeconomic status in the Korean population.

PMID- 22989277
TI  - Is baclofen a revolutionary medication in alcohol addiction management? Review
      and recent updates.
AB  - Baclofen, a gamma-aminobutyric acid (GABA)-B receptor agonist, represents a
      promising drug in alcohol addiction management. Animal models have shown its
      action at various stages of the process of alcohol addiction. Moreover, initial
      open and randomized controlled trials have shown the efficacy of 30 mg/day
      baclofen on alcohol craving, intake, and relapse prevention. It may also decrease
      alcohol withdrawal symptoms. However, these initial studies were conducted by the
      same Italian team; 2 American studies, using a different methodology, did not
      confirm these effects. Following recent reports by an alcohol-dependent French
      physician who treated himself with high doses (120-270 mg/day), claiming
      prolonged suppression of alcohol craving and absence of dependence symptoms,
      baclofen has since received wide media exposure in France where it has been
      called "the treatment for alcoholism." An open-label French study supports these
      findings. In addition, baclofen seems to be particularly interesting because of
      its safety and tolerance, even in patients with cirrhosis. Thus, baclofen should
      benefit from further studies of its biobehavioral mechanisms, dose-response
      effect, and indications in various alcoholic patient profiles.

PMID- 22989278
TI  - Exercise as an adjunct treatment for opiate agonist treatment: review of the
      current research and implementation strategies.
AB  - Opiate dependence is a significant public health concern linked to poor quality
      of life, comorbid psychiatric disorders, and high costs to society. Current
      opiate agonist treatments are an effective but limited intervention. Adjunctive
      interventions could improve and augment opiate agonist treatment outcomes,
      including drug abstinence, quality of life, and physical health. This article
      reviews exercise as an adjunctive intervention for opiate agonist treatment,
      especially in regards to improving mood and overall quality of life, while
      reducing other substance use. Poor adherence and dropout frequently prevent many
      individuals from garnering the many physical and mental health benefits of
      exercise. Strategies for implementing an exercise intervention, including safety
      considerations, are discussed.

PMID- 22989279
TI  - Pain is not associated with worse office-based buprenorphine treatment outcomes.
AB  - Physical pain is common among individuals seeking treatment for opioid
      dependence. Pain may negatively impact addiction treatment. The authors
      prospectively studied opioid-dependent individuals initiating office-based
      buprenorphine treatment, comparing buprenorphine treatment outcomes (treatment
      retention and opioid use) among participants with and without pain (baseline pain
      or persistent pain). Among 82 participants, 60% reported baseline pain and 38%
      reported persistent pain. Overall, treatment retention was 56% and opioid use
      decreased from 89% to 26% over 6 months. In multivariable analyses, the authors
      found no association between pain and buprenorphine treatment outcomes. Opioid
      dependent individuals with and without pain can achieve similar success with
      buprenorphine treatment.

PMID- 22989280
TI  - The antemortem neurobehavior in fatal paramethoxymethamphetamine usage.
AB  - Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug
      with a structure analogous to amphetamine and related psychostimulants. However,
      the neurobehavioral effect is only studied in experimental animals and is barely
      mentioned in human. The authors report the antemortem neurobehavioral
      manifestations in 8 patients with PMMA use. There were 2 different antemortem
      presentations. The first group of patients showed delirium, hypertalkativity, and
      incoherence speech and then turned into convulsion and death. They did not
      exhibit the typical hyperdopaminergic movement disorder. The second group of
      patients gradually fell asleep and then suffered respiratory or cardiovascular
      collapse. The heart blood PMMA level was higher in the second group than in the
      first group of patients. Forensic autopsy showed variable findings, ranging from
      no remarkable change to significant pathological damage similar to serotonin
      syndrome in both groups of patients. PMMA seems to enhance serotoninergism than
      dopaminergism, and exerts a concentration-related dual effect on human.

PMID- 22989281
TI  - Behavior, knowledge, and attitudes towards khat among Yemeni medical students and
      effects of a seminar.
AB  - This study describes khat behavior, knowledge, and attitudes among Yemeni medical
      students (MS) and the effects of a seminar. The students completed a survey (n =
      62); a subgroup participated in a discussion-based seminar and follow-up survey
      (n = 18). Although the students demonstrated knowledge about khat's health
      effects and considered it unacceptable for health professionals to chew khat,
      they disagreed that health professionals should advise patients to quit.
      Knowledge and attitudes improved post-seminar (not significant, except for a
      borderline significant increase in students correctly identifying khat as
      addictive; P = 0.063). Although effects were small, seminars may help health
      professionals address khat use in Yemen.

PMID- 22989283
TI  - Use of alcoholics anonymous as part of medical school education: students' and
      educators' perspectives.
AB  - The objective of this study was to discover the utility, barriers, and
      experiences with the use of Alcoholics Anonymous (AA) as a learning resource in
      the medical school curriculum. A third-year medical student cohort and a
      psychiatric educator group were queried about learned experiential lessons,
      attendance requirements, attitudes, and obstacles encountered. Forty-three
      educators, whose familiarity with AA varied widely, responded to the survey.
      Forty-seven percent required AA attendance and reported it was a positive
      experience for their students. Eighty-four percent felt students should attend AA
      and identified obstacles to its implementation. Separately, descriptive
      impressions of students (N = 95) who attended AA meetings were collected. Their
      responses were positive 46%, neutral 43%, or negative 11%. Respondents found AA
      meeting experiences generally positive, and although impediments to
      implementation of this experience still exist, they may be overcome with
      concerted efforts of psychiatric educators.

PMID- 22989282
TI  - Assessment of readiness to change and relationship to AUDIT score in a trauma
      population utilizing computerized alcohol screening and brief intervention.
AB  - Trauma patient readiness-to-change score and its relationship to the Alcohol Use
      Disorder Identification Test (AUDIT) score were assessed in addition to the
      feasibility of computerized alcohol screening and brief intervention (CASI). A
      bilingual computerized tablet for trauma patients was utilized and the data were
      analyzed using Stata. Twenty-five percent of 1145 trauma patients drank more than
      recommended and 4% were dependent. As many Spanish-speaking as English-speaking
      males did not drink, but a higher percentage of Spanish-speaking males drank more
      than recommended and were dependent. Half of patients who drank more than
      recommended rated themselves 8 or higher on a 10-point readiness-to-change scale.
      CASI also provided personalized feedback. A high percentage of trauma patients
      (92%) found CASI easy and a comfort in use (87%). Bilingual computerized
      technology for trauma patients is feasible, acceptable, and an innovative
      approach to alcohol screening, brief intervention, and referral to treatment in a
      tertiary care university.

PMID- 22989284
TI  - Addiction training in general psychiatry residency: a national survey.

PMID- 22989287
TI  - The future dominance of combination therapies: implications for today's medical
      research.

PMID- 22989286
TI  - Epilepsy-related mortality is low in children: a 30-year population-based study
      in Olmsted County, MN.
AB  - PURPOSE: Epilepsy is a common childhood neurologic disorder, affecting 0.5-1% of
      children. Increased mortality occurs due to progression of underlying disease,
      seizure-related accidents, suicide, status epilepticus, aspiration during
      seizures, and sudden unexplained death in epilepsy (SUDEP). Previous studies show
      mortality rates of 2.7-6.9 per 1,000 person-years. Potential risk factors include
      poor seizure control, intractable epilepsy, status epilepticus, tonic-clonic
      seizures, mental retardation, and remote symptomatic cause of epilepsy. Few
      population-based studies of mortality and SUDEP in childhood-onset epilepsy have
      been published. The purpose of this study is to report mortality and SUDEP from a
      30-year population-based cohort of children with epilepsy. METHODS: The Medical
      Diagnostic Index of the Rochester Epidemiology Project was searched for all codes
      related to seizure and convulsion in children living in Olmsted County, Minnesota
      and of ages birth through 17 years from 1980 through 2009. The medical records of
      these children were reviewed to identify all those with new-onset epilepsy, and
      to abstract other baseline and follow-up information. Potential risk factors
      including seizure type, epilepsy syndrome, history of status epilepticus, the
      presence and severity of neurologic impairment, and epilepsy outcome was
      reviewed. Epilepsy outcome was characterized by seizure frequency, number of
      antiseizure medications (antiepileptic drugs, AEDs) used, and number of AEDs
      failed due to lack of efficacy, and epilepsy intractability at 1 year and 2, 3,
      5, 10, 15, and 20 years after epilepsy onset. We followed all children through
      their most recent visit to determine vital status, cause of death, and whether
      autopsy was performed. KEY FINDINGS: From 1980 to 2009, there were 467 children
      age birth through 17 years diagnosed with epilepsy while residents of Olmsted
      County, Minnesota, and who had follow-up beyond the time of epilepsy diagnosis.
      Children were followed for a median of 7.87 years after the time of diagnosis
      (range 0.04-29.49 years) for a total of 4558.5 person-years. Sixteen (3.4%) of
      the children died, or 3.51 deaths per 1,000 person-years. Two deaths were
      epilepsy related (12.5%) for a rate of 0.44 per 1,000 person-years. One of these
      children died of probable SUDEP and one died of aspiration during a seizure. The
      remaining 14 deaths (87.5%) were caused by other complications of underlying
      disease. Several risk factors for mortality were found, including abnormal
      cognition, abnormal neurologic examination, structural/metabolic etiology for
      epilepsy, and poorly controlled epilepsy. SIGNIFICANCE: Although mortality in
      children with epilepsy was higher than what would be expected in the general
      pediatric population, death occurred significantly more in children with
      neurologic impairment and poorly controlled epilepsy. Epilepsy-related death,
      including SUDEP, was rare and mortality due to epilepsy alone was similar to the
      expected mortality in the general population (observed deaths = 2, expected
      deaths = 1.77; standardized mortality ratio 1.13, 95% confidence interval 0.19
      3.73, p = 0.86). By contrast, most children died of complications of the
      underlying neurologic disease or unrelated disease rather than the epilepsy.

PMID- 22989288
TI  - Multiplexed and electrically modulated plasmon laser circuit.
AB  - With unprecedented ability to localize electromagnetic field in time and space,
      the nanometer scale laser promises exceptionally broad scientific and
      technological innovation. However, as the laser cavity becomes subwavelength, the
      diffraction of light prohibits the directional emission, so-called the
      directionality, one of the fundamental attributes of the laser. Here, we have
      demonstrated a deep subwavelength waveguide embedded (WEB) plasmon laser that
      directs more than 70% of its radiation into an embedded semiconductor nanobelt
      waveguide with dramatically enhanced radiation efficiency. The unique
      configuration of WEB plasmon laser naturally integrates photonic and electronic
      functionality allowing both efficient electrical modulation and wavelength
      multiplexing. We have demonstrated a plasmonic circuit integrating five
      independently modulated multicolored plasmon laser sources multiplexed onto a
      single semiconductor nanobelt waveguide, illustrating the potential of plasmon
      lasers for large scale, ultradense photonic integration.

PMID- 22989289
TI  - Ecological and evolutionary genomics of marine photosynthetic organisms.
AB  - Environmental (ecological) genomics aims to understand the genetic basis of
      relationships between organisms and their abiotic and biotic environments. It is
      a rapidly progressing field of research largely due to recent advances in the
      speed and volume of genomic data being produced by next generation sequencing
      (NGS) technologies. Building on information generated by NGS-based approaches,
      functional genomic methodologies are being applied to identify and characterize
      genes and gene systems of both environmental and evolutionary relevance. Marine
      photosynthetic organisms (MPOs) were poorly represented amongst the early genomic
      models, but this situation is changing rapidly. Here we provide an overview of
      the recent advances in the application of ecological genomic approaches to both
      prokaryotic and eukaryotic MPOs. We describe how these approaches are being used
      to explore the biology and ecology of marine cyanobacteria and algae,
      particularly with regard to their functions in a broad range of marine
      ecosystems. Specifically, we review the ecological and evolutionary insights
      gained from whole genome and transcriptome sequencing projects applied to MPOs
      and illustrate how their genomes are yielding information on the specific
      features of these organisms.

PMID- 22989290
TI  - Metastatic non-seminomatous germ cell tumor with vena cava and vertebral
      involvement.

PMID- 22989292
TI  - Online detection of metals in environmental samples: comparing two concepts of
      bioluminescent bacterial biosensors.
AB  - In this study, we compared two bacterial biosensors designed for the
      environmental monitoring of metals: Lumisens III and Lumisens IV. These two
      biosensors are based on the same bacterial sensors (inducible or constitutive
      bacterial strains) but with a different conservation mode. The results showed
      that the biosensor Lumisens III using immobilized cells in agarose hydrogel,
      allowed to detect artificial mercury contaminations on the limited period of 7
      days in laboratory conditions with a reproducibility of 40%. With environmental
      samples, bioluminescence of the immobilized bacteria inside the biosensor was
      strongly limited by the environmental microflora because of the lack of oxygen,
      limiting the use of the biosensor to 2 days. The biosensor of the last
      generation, Lumisens IV, using freeze-dried bacteria in a disposable card allowed
      a stable detection during 10 days with 3% of reproducibility of the
      bioluminescence signal both in laboratory conditions and environmental samples.
      One analysis was performed in only 90 min against 360 min for Lumisens III.
      Nevertheless, the lack of specificity of the promoter, which regulates the
      bioluminescent reporter genes, limits the metal detection. We addressed the
      problem by using Lumisens IV and a data analysis software namely Metalsoft,
      developed in previous works. Thanks to this analytical software, Lumisens IV was
      a reliable online biosensor for the multidetection of Cd, As, Hg, and Cu.

PMID- 22989294
TI  - Gangrenous appendicitis presenting as acute abdominal pain in a patient on
      automated peritoneal dialysis: a case report.
AB  - INTRODUCTION: Presentations of abdominal pain in patients on peritoneal dialysis
      deserve maximal attention and careful differential diagnosis on admittance to
      medical care. In this case report a gangrenous appendicitis in a patient on
      automated peritoneal dialysis is presented. CASE PRESENTATION: We report the case
      of a 38-year-old Caucasian man with end-stage renal disease who was on automated
      peritoneal dialysis and developed acute abdominal pain and cloudy peritoneal
      dialysate. Negative microbiological cultures of the peritoneal dialysis fluid and
      an abdominal ultrasonography misleadingly led to a diagnosis of culture negative
      peritonitis. It was decided to remove the peritoneal catheter but the clinical
      situation of the patient did not improve. An explorative laparotomy was then
      carried out; diffuse peritonitis and gangrenous appendicitis were found. An
      appendectomy was performed. Myocardial infarction and sepsis developed, and the
      outcome was fatal. CONCLUSION: A peritoneal dialysis patient with abdominal pain
      that persists for more than 48 hours after the usual antibiotic protocol for
      peritoneal dialysis-related peritonitis should immediately alert the physician to
      the possibility of peritonitis caused by intra-abdominal pathology. Not only
      peritoneal catheter removal is indicated in patients whose clinical features
      worsen or fail to resolve with the established intra-peritoneal antibiotic
      therapy but, after 72 hours, an early laparoscopy should be done and in a case of
      correct indication (intra-abdominal pathology) an early explorative laparotomy.

PMID- 22989293
TI  - Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but
      not associated with left ventricular function and myocardial fibrosis as assessed
      by cardiac magnetic resonance imaging.
AB  - BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is common in
      cardiovascular diseases and associated with hypertension, renal dysfunction
      and/or heart failure. There is a paucity of data about the prevalence and the
      role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and
      chronic kidney disease (CKD). We investigated the prevalence in patients with
      combined CHF/CKD and its association with renal function, cardiac dysfunction and
      the presence and extent of myocardial fibrosis. METHODS: The EPOCARES study
      (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic
      patients with combined CHF/CKD. Eligible subjects underwent combined cardiac
      magnetic resonance imaging (cMRI), including late gadolinium enhancement, with
      magnetic resonance angiography of the renal arteries (MRA). RESULTS: MR study was
      performed in 37 patients (median age 74 years, eGFR 37.4 +/- 15.6 ml/min, left
      ventricular ejection fraction (LVEF) 43.3 +/- 11.2%), of which 21 (56.8%) had
      ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe
      ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA).
      There were no differences in age, NT-proBNP levels and medication profile between
      patients with ARAS versus those without. Renal function declined with the
      severity of ARAS (p = 0.03), although this was not significantly different
      between patients with ARAS versus those without. Diabetes mellitus was more
      prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p =
      0.04). The presence and extent of late gadolinium enhancement, depicting
      myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p =
      0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was
      there a difference in the presence of an ischemic pattern of late enhancement in
      patients with ARAS versus those without. CONCLUSIONS: ARAS is prevalent in
      combined CHF/CKD and its severity is associated with a decline in renal function.
      However, its presence does not correlate with a worse LVEF, a higher left
      ventricular mass or with the presence and extent of myocardial fibrosis. Further
      research is required for the role of ARAS in the pathophysiology of combined
      chronic heart and renal failure.

PMID- 22989296
TI  - Primary and secondary metabolism in the sun-exposed peel and the shaded peel of
      apple fruit.
AB  - The metabolism of carbohydrates, organic acids, amino acids and phenolics was
      compared between the sun-exposed peel and the shaded peel of apple fruit.
      Contents of sorbitol and glucose were higher in the sun-exposed peel, whereas
      those of sucrose and fructose were almost the same in the two peel types. This
      was related to lower sorbitol dehydrogenase activity and higher activities of
      sorbitol oxidase, neutral invertase and acid invertase in the sun-exposed peel.
      The lower starch content in the sun-exposed peel was related to lower sucrose
      synthase activity early in fruit development. Dark respiratory metabolism in the
      sun-exposed peel was enhanced by the high peel temperature due to high light
      exposure. Activities of most enzymes in respiratory metabolism were higher in the
      sun-exposed peel, but the concentrations of most organic acids were relatively
      stable, except pyruvate and oxaloacetate. Due to the different availability of
      carbon skeletons from dark respiration in the two peel types, amino acids with
      higher C/N ratios are accumulated in the sun-exposed peel whereas those with
      lower C/N ratios are accumulated in the shaded peel. Contents of anthocyanins and
      flavonols and activities of phenylalanine ammonia-lyase, UDP-galactose:flavonoid
      3-O-glucosyltransferase and several other enzymes were higher in the sun-exposed
      peel than in the shaded peel, indicating the entire phenylpropanoid pathway is
      upregulated in the sun-exposed peel. Comprehensive analyses of the metabolites
      and activities of enzymes involved in primary metabolism and secondary metabolism
      have allowed us to gain a full picture of the metabolic network in the two peel
      types under natural light exposure.

PMID- 22989297
TI  - Examples of regioselective anion recognition among a family of two-, three-, and
      four-"armed" bis-, tris-, and tetrakis(thioureido) [n]polynorbornane hosts.
AB  - A family of conformationally preorganized, [n]polynorbornane-based anion hosts
      1a,b-6a,b have been synthesized. The series includes receptors with 4, 8, and 12
      H-bond donors. Using (1)H NMR titration techniques, evaluation of the new hosts
      against a series of alkyl and aryl dicarboxylates as well as a range of
      phosphoanionic species has revealed that the tris(thioureido) hosts (in
      particular 3a) are capable of regioselectively binding dicarboxylates and
      pyrophosphate (H(2)PPi(2-)).

PMID- 22989298
TI  - Diffusion tensor imaging in elderly patients with idiopathic normal pressure
      hydrocephalus or Parkinson's disease: diagnosis of gait abnormalities.
AB  - BACKGROUND: Gait abnormalities in the elderly, characterized by short steps and
      frozen gait, can be caused by several diseases, including idiopathic normal
      pressure hydrocephalus (INPH), and Parkinson's disease (PD). We analyzed the
      relationship between these two conditions and their association with gait
      abnormalities using laboratory test data and findings from diffusion tensor
      imaging (DTI). METHODS: The study involved 10 patients with INPH, 18 with PD, and
      10 healthy individuals (control group). Fractional anisotropy (FA) of five brain
      areas was measured and compared among the three groups. In addition, the
      association of INPH and PD with gait capability, frontal lobe function, and FA of
      each brain area was evaluated. RESULTS: The INPH group had significantly lower FA
      for anterior thalamic radiation (ATR) and forceps minor (Fmin) as compared to the
      PD group. The gait capability correlated with ATR FA in the INPH and PD groups.
      We found that adding DTI to the diagnosis assisted the differential diagnosis of
      INPH from PD, beyond what could be inferred from ventricular size alone.
      CONCLUSIONS: We expect that DTI will provide a useful tool to support the
      differential diagnosis of INPH and PD and their respective severities.

PMID- 22989295
TI  - Pinocembrin protects against beta-amyloid-induced toxicity in neurons through
      inhibiting receptor for advanced glycation end products (RAGE)-independent
      signaling pathways and regulating mitochondrion-mediated apoptosis.
AB  - BACKGROUND: It is known that amyloid-beta peptide (Abeta) plays a pivotal role in
      the pathogenesis of Alzheimer's disease (AD). Interaction between Abeta and the
      receptor for advanced glycation end products (RAGE) has been implicated in
      neuronal degeneration associated with this disease. Pinocembrin, a flavonoid
      abundant in propolis, has been reported to possess numerous biological activities
      beneficial to health. Our previous studies have demonstrated that pinocembrin has
      neuroprotective effects on ischemic and vascular dementia in animal models. It
      has been approved by the State Food and Drug Administration of China for clinical
      use in stroke patients. Against this background, we investigated the effects of
      pinocembrin on cognitive function and neuronal protection against Abeta-induced
      toxicity and explored its potential mechanism. METHODS: Mice received an
      intracerebroventricular fusion of Abeta25-35. Pinocembrin was administrated
      orally at 20 mg/kg/day and 40 mg/kg/day for 8 days. Behavioral performance,
      cerebral cortex neuropil ultrastructure, neuronal degeneration and RAGE
      expression were assessed. Further, a RAGE-overexpressing cell model and an AD
      cell model were used for investigating the mechanisms of pinocembrin. The
      mechanisms underlying the efficacy of pinocembrin were conducted on target
      action, mitochondrial function and potential signal transduction using
      fluorescence-based multiparametric technologies on a high-content analysis
      platform. RESULTS: Our results showed that oral administration of pinocembrin
      improved cognitive function, preserved the ultrastructural neuropil and decreased
      neurodegeneration of the cerebral cortex in Abeta25-35-treated mice. Pinocembrin
      did not have a significant effect on inhibiting Abeta1-42 production and
      scavenging intracellular reactive oxygen species (ROS). However, pinocembrin
      significantly inhibited the upregulation of RAGE transcripts and protein
      expression both in vivo and in vitro, and also markedly depressed the activation
      of p38 mitogen-activated protein kinase (MAPK)-MAPKAP kinase-2 (MK2)-heat shock
      protein 27 (HSP27) and stress-activated protein kinase (SAPK)/c-Jun N-terminal
      kinase (JNK)-c-Jun pathways and the downstream nuclear factor kappaB (NFkappaB)
      inflammatory response subsequent to Abeta-RAGE interaction. In addition,
      pinocembrin significantly alleviated mitochondrial dysfunction through improving
      mitochondrial membrane potential and inhibiting mitochondrial oxidative stress,
      and regulated mitochondrion-mediated apoptosis by restoration of B cell lymphoma
      2 (Bcl-2) and cytochrome c and inactivation of caspase 3 and caspase 9.
      CONCLUSIONS: Pinocembrin was shown to infer cognitive improvement and neuronal
      protection in AD models. The mechanisms of action of the compound were
      illustrated on RAGE-dependent transduction inhibition and mitochondrion
      protection. It appears to be a promising candidate for the prevention and therapy
      of AD.

PMID- 22989300
TI  - The meaning of craft: craft makers' descriptions of craft as an occupation.
AB  - The aim of this study is to examine how craft makers describe the meaning of
      craft as an activity in relation to their well-being. The study is based on an
      analysis of the written narratives of 92 textile craft makers aged 16 to 84.
      Based on the results, the well-being enhancing nature of craft as a meaningful
      occupation for those interested in crafting is evident. The significance of craft
      making as an occupation is described by the following three themes: (a) "the
      meaning and value of crafts", (b) "the feelings experienced during craft
      activity", and (c) "the holisticity and intentionality of craft-making". As an
      activity and a metaphor, craft making helped the participants to adjust to life
      situations. Elements of craft that enhance well-being can be traced to both the
      artefacts and the sense of achievement gained in producing them. The effects of
      craft include personal growth, development of physical and cognitive skills,
      control of one's body, thoughts, and feelings, as well as cultural and social
      awareness. The results indicate that the participants noticed the significance of
      craft as an agony- and stress-reducing and mind-calming activity. Holistic craft
      and ordinary craft played different roles in maintaining well-being.

PMID- 22989299
TI  - An efficient strategy for cell-based antibody library selection using an
      integrated vector system.
AB  - BACKGROUND: Cell panning of phage-displayed antibody library is a powerful tool
      for the development of therapeutic and imaging agents since disease-related cell
      surface proteins in native complex conformation can be directly targeted. Here,
      we employed a strategy taking advantage of an integrated vector system which
      allows rapid conversion of scFv-displaying phage into scFv-Fc format for
      efficient cell-based scFv library selection on a tetraspanin protein, CD9.
      RESULTS: A mouse scFv library constructed by using a phagemid vector, pDR-D1 was
      subjected to cell panning against stable CD9 transfectant, and the scFv
      repertoire from the enriched phage pool was directly transferred to a mammalian
      cassette vector, pDR-OriP-Fc1. The resulting constructs enabled transient
      expression of enough amounts of scFv-Fcs in HEK293E cells, and flow cytometric
      screening of binders for CD9 transfectant could be performed simply by using the
      culture supernatants. All three clones selected from the screening showed correct
      CD9-specificity. They could immunoprecipitate CD9 molecules out of the
      transfectant cell lysate and correctly stain endogenous CD9 expression on cancer
      cell membrane. Furthermore, competition assay with a known anti-CD9 monoclonal
      antibody (mAb) suggested that the binding epitopes of some of them overlap with
      that of the mAb which resides within the large extracellular loop of CD9.
      CONCLUSIONS: This study demonstrates that scFv-Fc from mammalian transient
      expression can be chosen as a reliable format for rapid screening and validation
      in cell-based scFv library selection, and the strategy described here will be
      applicable to efficient discovery of antibodies to diverse cell-surface targets.

PMID- 22989301
TI  - Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B
      virus transgenic mice model.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) overlapping with
      chronic hepatitis B virus (HBV) infection is undergoing a rapid increase in
      China. Therefore, the establishment and character of an animal model with both
      NAFLD and chronic HBV infection has become an urgent task. METHODS: Mice with
      chronic HBV genotype B infection were established with a microinjection of
      oocytes. Transgenic and nontransgenic mice were then randomized into groups of
      NAFLD + HBV, HBV, NAFLD, and control and were treated with high-fat diets or
      common forage. At 8, 16, and 24 weeks, characteristics of NAFLD were evaluated by
      physical indices, liver function tests, glycolipid metabolism, and
      histopathological scoring. Viral dynamics were also analyzed by HBV-DNA and HBV
      related antigens. RESULTS: Hepatitis B surface antigen (HBsAg) and hepatitis B e
      antigen (HBeAg) were expressed, and HBV-DNA was replicated in HBV transgenic mice
      at different stages in the serum and liver. Hepatic steatosis was only induced
      after exposure of the mice to high-fat diets, and no obvious pathological changes
      occurred in the HBV group from 8 to 24 weeks. Compared to mice with HBV alone,
      significant reductions in serum levels of HBV-DNA, HBsAg and HBeAg occurred in
      the NAFLD + HBV group after 24 weeks (all P < 0.05). Nevertheless, the NAFLD and
      NAFLD + HBV groups shared comparable physical and metabolic disorders and similar
      steatotic, inflammatory and fibrotic characteristics in the liver. CONCLUSION:
      High-fat diets and transgenic operations on the HBV genotype B induced a rodent
      model of NAFLD overlapping with chronic HBV infection, and this model reduces the
      HBV viral factors but not the metabolic and histologic features.

PMID- 22989302
TI  - Multinuclear NMR study of the effect of acid concentration on ion transport in
      phosphoric acid doped poly(benzimidazole) membranes.
AB  - (1)H and (31)P NMR spectra, line widths, spin-lattice relaxation times (T(1)),
      and (1)H self-diffusion coefficients (D) were determined for two distinct
      poly(benzimidazole) (PBI) proton exchange membranes (PEM), para-PBI and dihydroxy
      PBI (2OH-PBI), both incorporating varying concentrations of phosphoric acid. The
      study was performed over the temperature range of 20-180  degrees C, for
      phosphoric acid concentrations of 30, 50, and 70 wt %. Of the two samples, less
      mobility was indicated for the 2OH-PBI compared with the para-PBI at all acid
      concentrations. It was also observed that increasing the acid content resulted in
      an increase in the temperature at which the T(1) minimum or plateau occurred.
      (31)P spectra reveal the presence of pyrophosphates and in the case of the 50 and
      70 wt % para-PBI samples higher oligomers such as tripolyphosphates. (1)H D data
      showed the 30 wt % para-PBI having almost identical values as the 70 wt % 2OH-PBI
      over the entire temperature range. In general, stronger short- and long-range
      interactions were observed in the 2OH-PBI matrix, yielding reduced translational
      proton transport compared to that of para-PBI. While these stronger interactions
      hinder translational proton diffusion, they could enhance proton transport by the
      Grotthuss or structure diffusion mechanism, the more favorable transport
      mechanism. Activation energies obtained from the (1)H D data supports a proton
      hopping mechanism, with possible assistance from fast exchange between phosphate
      groups.

PMID- 22989303
TI  - Nursing competence: psychometric evaluation using Rasch modelling.
AB  - AIM: To test the psychometric properties and evaluate the German version of the
      Nurse Competence Scale. BACKGROUND: Nursing competence is an important factor for
      high-quality healthcare. However, there are only few instruments available, which
      try to assess nurse competence and there is limited knowledge about the
      psychometric quality of any of these instruments. DESIGN: A cross-sectional
      survey of 679 nurses was used. METHOD: Analysis of the psychometric properties of
      the 73-item Nurse Competence Scale was undertaken using confirmatory factor
      analyses and Rasch modelling with data generated in a study in 2007. RESULTS: The
      7-factor model of the Nurse Competence Scale could not be confirmed. However, six
      scales consisting of 54 items demonstrated adequate fit to the Rasch model. The
      six subscales could also be combined into an overall competence scale.
      CONCLUSIONS: There are concerns about the psychometric properties of the Nurse
      Competence Scale. The reduced set of items removes redundancy among items, is
      free from item bias and constitutes six unidimensional scales.

PMID- 22989304
TI  - Expression, purification, and reconstitution of the voltage-sensing domain from
      Ci-VSP.
AB  - The voltage-sensing domain (VSD) is the common scaffold responsible for the
      functional behavior of voltage-gated ion channels, voltage sensitive enzymes, and
      proton channels. Because of the position of the voltage dependence of the
      available VSD structures, at present, they all represent the activated state of
      the sensor. Yet in the absence of a consensus resting state structure, the
      mechanistic details of voltage sensing remain controversial. The voltage
      dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that
      at 0 mV it presumably populates the putative resting state. Appropriate
      biochemical methods are an essential prerequisite for generating sufficient
      amounts of Ci-VSD protein for high-resolution structural studies. Here, we
      present a simple and robust protocol for the expression of eukaryotic Ci-VSD in
      Escherichia coli at milligram levels. The protein is pure, homogeneous,
      monodisperse, and well-folded after solubilization in Anzergent 3-14 at the
      analyzed concentration (~0.3 mg/mL). Ci-VSD can be reconstituted into liposomes
      of various compositions, and initial site-directed spin labeling and electron
      paramagnetic resonance (EPR) spectroscopic measurements indicate its first
      transmembrane segment folds into an alpha-helix, in agreement with the homologous
      region of other VSDs. On the basis of our results and enhanced relaxation EPR
      spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in
      proteoliposomes, precluding straightforward application of transmembrane voltages
      in combination with spectroscopic methods. Nevertheless, these results represent
      an initial step that makes the resting state of a VSD accessible to a variety of
      biophysical and structural approaches, including X-ray crystallography,
      spectroscopic methods, and electrophysiology in lipid bilayers.

PMID- 22989305
TI  - Acute mediastinitis: evaluation of clinical risk factors for death in surgically
      treated patients.
AB  - BACKGROUND: Acute mediastinitis (AM) is the most lethal form of infection within
      the thorax. The authors of this study, using statistical tools, made an attempt
      to determine the most important clinical risk factors in retrospective material
      of patients treated surgically due to AM. METHODS: A total of 44 consecutive
      patients with AM were subjected to surgery. The aetiology was differentiated:
      iatrogenic (19), traumatic (11), descending mediastinitis (9) and neoplastic (5).
      A statistical analysis was performed using chi-square test with Yates correction
      and analysis of variance test to investigate the correlation between mortality
      and selected risk factors such as age, gender, aetiology, microbiology, delay
      between the diagnosis and surgery, coexisting diseases and the kind and number of
      post-operative complications. RESULTS: The general death rate was 31.82%.
      Aetiology was associated with mortality: neoplastic (100%), descending (33.3%),
      iatrogenic (26.3%) and post-traumatic (9.1%). The following types of bacteria
      were isolated: aerobes (65.9%), anaerobes (25%) and mixed flora (9.1%). The
      prognosis was not related to age, gender or the kind of the pathogen. The risk of
      death increased depending on the number of preoperative co-morbidities (P =
      0.0446), particularly on the occurrence of a neoplasm (P = 0.0104). Early
      qualification for surgery (<24 h) resulted in lower death rate (P = 0.085).
      Manifestation of more than two post-operative complications (P = 0.0007) should
      be listed as one of the most negative risk factors. CONCLUSIONS: The knowledge of
      negative prognostic factors can appear to be a crucial tool enabling one to work
      out a better therapeutic strategy for high-risk patients with AM.

PMID- 22989306
TI  - In-house preparation of hydrogels for batch affinity purification of glutathione
      S-transferase tagged recombinant proteins.
AB  - BACKGROUND: Many branches of biomedical research find use for pure recombinant
      proteins for direct application or to study other molecules and pathways.
      Glutathione affinity purification is commonly used to isolate and purify
      glutathione S-transferase (GST)-tagged fusion proteins from total cellular
      proteins in lysates. Although GST affinity materials are commercially available
      as glutathione immobilized on beaded agarose resins, few simple options for in
      house production of those systems exist. Herein, we describe a novel method for
      the purification of GST-tagged recombinant proteins. RESULTS: Glutathione was
      conjugated to low molecular weight poly(ethylene glycol) diacrylate (PEGDA) via
      thiol-ene "click" chemistry. With our in-house prepared PEGDA:glutathione
      (PEGDA:GSH) homogenates, we were able to purify a glutathione S-transferase (GST)
      green fluorescent protein (GFP) fusion protein (GST-GFP) from the soluble
      fraction of E. coli lysate. Further, microspheres were formed from the PEGDA:GSH
      hydrogels and improved protein binding to a level comparable to purchased GSH
      agarose beads. CONCLUSIONS: GSH containing polymers might find use as in-house
      methods of protein purification. They exhibited similar ability to purify GST
      tagged proteins as purchased GSH agarose beads.

PMID- 22989307
TI  - Percutaneous transgastric traction-assisted esophageal endoscopic submucosal
      dissection: a randomized controlled trial in a porcine model.
AB  - OBJECTIVES: Endoscopic submucosal dissection (ESD) is a technically difficult,
      hazardous, and time-consuming treatment option for superficial neoplasms of the
      esophagus. The aim of this pilot study was to determine the effectiveness and
      safety of percutaneous transgastric traction (PTT)-assisted ESD, a method that
      overcomes the drawbacks of conventional ESD, in a porcine model. METHODS: Six
      domestic pigs (25-30 kg) were used in the study. In each animal, two 5-cm-long
      esophageal areas were assigned randomly for resection by conventional ESD or PTT
      assisted ESD. The PTT method was designed to offer esophageal mucosal traction
      directed toward the stomach. The wire was introduced into the stomach through a
      percutaneous transgastric cannula and was fixed on the resected esophageal
      mucosa. RESULTS: Submucosal dissection in the traction group required only half
      the time of that in the non-traction group (mean dissection time 596.0 vs. 1127.3
      s, respectively; p = 0.01). At necropsy, no differences in the incidence of
      perforation or bleeding were found between two groups. CONCLUSIONS: The PTT
      method can enhance the speed of submucosal dissection for esophageal ESD to
      completely remove large areas of resected mucosa.

PMID- 22989308
TI  - An automated device for appetitive conditioning in zebrafish (Danio rerio).
AB  - An automated device and a procedure for the operant conditioning individual
      zebrafish were developed. The key feature of this procedure was the construction
      of a simple, inexpensive feeder that can deliver extremely small amounts of food,
      thus preventing rapid satiation. This allows the experimenter to run multiple
      trails in a single test session and multiple sessions in one day. In addition,
      small response keys made from acryl rods and fiber sensors were developed that
      were sufficiently sensitive to detect fish contact. To illustrate the efficiency
      and utility of the device for traditional learning paradigms, we trained
      zebrafish in a fixed ratio schedule where subjects were reinforced with food
      after 10 responses. Zebrafish reliably responded on the response key for sessions
      that lasted as long 80-reinforcements. They also showed the traditional "break
      and run" response pattern that has been found in many species. These results show
      that this system will be valuable for behavioral studies with zebrafish,
      especially for experiments that need many repeated trials using food reinforcer
      in a session. The present system can be used for sensory and learning
      investigations, as well applications in behavioral pharmacology, behavioral
      genetics, and toxicology where the zebrafish is becoming the vertebrate model of
      choice.

PMID- 22989309
TI  - Dual carbon-chlorine stable isotope investigation of sources and fate of
      chlorinated ethenes in contaminated groundwater.
AB  - Chlorinated ethenes (CEs) are ubiquitous groundwater contaminants, yet there
      remains a need for a method to efficiently monitor their in situ degradation. We
      report here the first field application of combined stable carbon and chlorine
      isotope analysis of tetrachloroethene (PCE) and trichloroethene (TCE) to
      investigate their biodegradation in a heavily contaminated aquifer. The two
      dimensional Compound Specific Isotope Analysis (2D-CSIA) approach was facilitated
      by a recently developed gas chromatography-quadrupole mass spectrometry (GCqMS)
      method for delta(37)Cl determination. Both C and Cl isotopes showed evidence of
      ongoing PCE transformation. Applying published C isotope enrichment factors
      (epsilon(C)) enabled evaluation of the extent of in situ PCE degradation (11
      78%). We interpreted C and Cl isotopes using a numerical reactive transport model
      along a 60-m flow path. It revealed that combined PCE and TCE mass load was
      dechlorinated by less than 10%, and that cis-dichloroethene was not further
      dechlorinated. Furthermore, the 2D-CSIA approach allowed estimation of Cl isotope
      enrichment factors epsilon(Cl) (-7.8 to -0.80/00) and characteristic
      epsilon(Cl)/epsilon(C) values (0.42-1.12) for reductive PCE dechlorination at
      this field site. This investigation demonstrates the benefit of 2D-CSIA to assess
      in situ degradation of CEs and the applicability of Cl isotope fractionation to
      evaluate PCE and TCE dechlorination.

PMID- 22989311
TI  - Editorial comment from Dr Montironi et al. to malignant mixed epithelial and
      stromal tumor of the kidney: report of the first male case.

PMID- 22989310
TI  - Construction of the octose 8-phosphate intermediate in lincomycin A biosynthesis:
      characterization of the reactions catalyzed by LmbR and LmbN.
AB  - Lincomycin A is a potent antimicrobial agent noted for its unusual C1
      methylmercapto-substituted 8-carbon sugar. Despite its long clinical history for
      the treatment of Gram-positive infections, the biosynthesis of the C(8)-sugar,
      methylthiolincosamide (MTL), is poorly understood. Here, we report our studies of
      the two initial enzymatic steps in the MTL biosynthetic pathway leading to the
      identification of D-erythro-D-gluco-octose 8-phosphate as a key intermediate. Our
      experiments demonstrate that this intermediate is formed via a transaldol
      reaction catalyzed by LmbR using D-fructose 6-phosphate or D-sedoheptulose 7
      phosphate as the C(3) donor and D-ribose 5-phosphate as the C(5) acceptor.
      Subsequent 1,2-isomerization catalyzed by LmbN converts the resulting 2-keto C(8)
      sugar (octulose 8-phosphate) to octose 8-phosphate. These results provide, for
      the first time, in vitro evidence for the biosynthetic origin of the C(8)
      backbone of MTL.

PMID- 22989312
TI  - Direct monitoring of the role played by a stabilizer in a solid sample of polymer
      using direct analysis in real time mass spectrometry: the case of Irgafos 168 in
      polyethylene.
AB  - Direct analysis in real time (DART) ionization method is used with a time-of
      flight (TOF) mass spectrometer to perform the analysis of industrial polyethylene
      pellets free of additives or containing Irgafos 168 as stabilizing agent without
      any sampling step. The developed analytical method uses the [M + H](+) ion of the
      bis(2-ethylhexyl) phthalate (DEHP) for performing the exact mass measurements of
      the stabilizer and polymer ions using the mass drift compensation procedure
      available on the AccuTOF mass spectrometer. DEHP is in fact a plastic contaminant
      always presents on the mass spectra of the analyzed samples. The mass spectra
      allow one to characterize either the ions of the polyethylene and that of the
      Irgafos. The analysis of thermally treated samples show that the polymer does not
      undergo any degradation when the Irgafos is present in the bulk of the material,
      and the role played by the Irgafos 168 is that of an oxygen trapping agent. Under
      UV exposure, the DART-TOF MS analyses performed on the exposed polyethylene
      pellets shows that the Irgafos 168 behavior toward the UV radiations is different
      since this one reacts by cleavages of its P-O bonds to prevent the degradation of
      the polymer. These interpretations are supported by all the elemental formula
      determination of the detected ions.

PMID- 22989313
TI  - Speciation analysis of aqueous nanoparticulate diclofenac complexes by solid
      phase microextraction.
AB  - The dynamic sorption of an organic compound by nanoparticles (NPs) is analyzed by
      solid-phase microextraction (SPME) for the example case of the pharmaceutical
      diclofenac in dispersions of impermeable (silica, SiO(2)) and permeable (bovine
      serum albumin, BSA) NPs. It is shown that only the protonated neutral form of
      diclofenac is accumulated in the solid phase, and hence this species governs the
      eventual partition equilibrium. On the other hand, the rate of the solid/water
      partition equilibration is enhanced in the presence of the sorbing nanoparticles
      of SiO(2) and BSA. This feature demonstrates that the NPs themselves do not enter
      the solid phase to any appreciable extent. The enhanced rate of attainment of
      equilibrium is due to a shuttle-type of contribution from the NP-species to the
      diffusive supply of diclofenac to the water/solid interface. For both types of
      nanoparticulate complexes, the rate constant for desorption (k(des)) of bound
      diclofenac was derived from the measured thermodynamic affinity constant and a
      diffusion-limited rate of adsorption. The computed k(des) values were found to be
      sufficiently high to render the NP-bound species labile on the effective time
      scale of SPME. In agreement with theoretical prediction, the experimental results
      are quantitatively described by fully labile behavior of the
      diclofenac/nanoparticle system and an ensuing accumulation rate controlled by the
      coupled diffusion of neutral, deprotonated, and NP-bound diclofenac species.

PMID- 22989314
TI  - Predicting having condoms available among adolescents: the role of personal norm
      and enjoyment.
AB  - OBJECTIVES: Having condoms available has been shown to be an important predictor
      of condom use. We examined whether or not personal norm and goal enjoyment
      contribute to predicting having condoms available in the context of cognition
      specified by the theory of planned behaviour (TPB). DESIGN: Prospective survey
      study, with a baseline and follow-up measurement (at 3 months). METHODS: Data
      were gathered using an online survey. In total 282 adolescents (mean age = 15.6,
      74% female adolescents) completed both questionnaires. At baseline, demographics,
      sexual experience, condom use, TPB variables, descriptive norm, personal norm,
      and enjoyment towards having condoms available were measured. At T2 (3 months
      later) having condoms available was measured. Direct and moderating effects of
      personal norm and goal enjoyment were examined by means of hierarchical linear
      regression analyses. RESULTS: Regression analyses yielded a direct effect of self
      efficacy and personal norm on condom availability. In addition, moderation of the
      intention-behaviour relation by goal enjoyment added to the variance explained.
      The final model explained approximately 35% of the variance in condom
      availability. CONCLUSIONS: Personal norm and goal enjoyment add to the predictive
      utility of a TPB model of having condoms available and may be useful intervention
      targets. STATEMENT OF CONTRIBUTION: What is already known about this subject?
      Having condoms available is an important prerequisite for actual condom use. The
      theory of planned behaviour has successfully been applied to explain condom
      availability behaviour. The theory of planned behaviour has been criticized for
      not adequately taking into account affective motivation. What does this study
      add? Personal norm and goal enjoyment add to the predictive utility of the model.
      Personal norm explains condom availability directly, enjoyment increases
      intention enactment. Personal norm and goal enjoyment therefore are useful
      intervention targets.

PMID- 22989315
TI  - Cryptic diversity of the 'cosmopolitan' harpacticoid copepod Nannopus palustris:
      genetic and morphological evidence.
AB  - Nannopus palustris Brady, 1880 is a free-living widely distributed harpacticoid
      copepod, which has been formerly assumed to be a single, cosmopolitan but highly
      variable species. We compared several geographically distant N. palustris
      populations in terms of their morphology and genetics. Populations from the White
      Sea (WS), the North Sea (NS), the Black Sea (BS) and two sympatric morphs from
      South Carolina, USA (SC notched and SC straight morphs), were considered. The NS,
      BS and to a lesser extent SC notched specimens were morphologically similar and
      partly coincided to the 'canonical' description of the species. By contrast, WS
      population showed remarkable anatomical and morphometric peculiarities that
      correspond to some earlier descriptions. Genetic analyses of mitochondrial
      (cytochrome b) and nuclear (28S rDNA) genes demonstrated the significant
      distinctness among WS, both SC and (NS+BS) populations, the latter two being
      genetically indistinguishable. Concordance between mitochondrial and nuclear gene
      trees and morphological data supports that N. palustris is in fact composed of
      several pseudo-sibling species, which are genetically and morphologically
      divergent. Neither correlation between genetic divergence and geographical
      distance nor significant intrapopulation diversity was found for these species.
      Taxonomic status, distribution and phylogenetic relationships of the species
      within the Nannopus genus need to be reconsidered. A further subdivision of
      species complexes might have important implications for the analysis of
      biodiversity of benthic copepods and consequently for the interpretation of their
      (species-specific) ecological function.

PMID- 22989316
TI  - Effective intravenous immunoglobulin therapy for Churg-Strauss syndrome (allergic
      granulomatous angiitis) complicated by neuropathy of the eighth cranial nerve: a
      case report.
AB  - INTRODUCTION: We report the case of a patient with Churg-Strauss syndrome with
      eighth cranial nerve palsy. Vestibulocochlear nerve palsy is extremely rare in
      Churg-Strauss syndrome. To the best of our knowledge, only one case of
      complicated neuropathy of the eighth cranial nerve has been described in a
      previous report presenting an aggregate calculation, but no differentiation
      between polyarteritis nodosa and Churg-Strauss syndrome was made. High-dose
      immunoglobulin was administered to our patient, and her neuropathy of the eighth
      cranial nerve showed improvement. CASE PRESENTATION: At the age of 46, a Japanese
      woman developed Churg-Strauss syndrome that later became stable with low-dose
      prednisolone treatment. At the age of 52, she developed sudden difficulty of
      hearing in her left ear, persistent severe rotary vertigo, and mononeuritis
      multiplex. At admission, bilateral perceptive deafness of about 80dB and
      eosinophilia of 4123/MUL in peripheral blood were found. A diagnosis of cranial
      neuropathy of the eighth cranial nerve associated with exacerbated Churg-Strauss
      syndrome was made. Although high doses of steroid therapy alleviated the
      inflammatory symptoms and markers, the vertigo and bilateral hearing loss
      remained. Addition of a high-dose immunoglobulin finally resulted in marked
      alleviation of the symptoms associated with neuropathy of the eighth cranial
      nerve. CONCLUSIONS: A high dose of immunoglobulin therapy shows favorable effects
      in neuropathy of the eighth cranial nerve, but no reports regarding its efficacy
      in cranial neuropathy have been published.

PMID- 22989317
TI  - Temperature interactions with transpiration response to vapor pressure deficit
      among cultivated and wild soybean genotypes.
AB  - A key strategy in soybean drought research is increased stomatal sensitivity to
      high vapor pressure deficit (VPD), which contributes to the 'slow wilting' trait
      observed in the field. These experiments examined whether temperature of the
      growth environment affected the ability of plants to respond to VPD, and thus
      control transpiration rate (TR). Two soybean [Glycine max (L.) Merr.] and four
      wild soybean [Glycine soja (Sieb. and Zucc.)] genotypes were studied. The TR was
      measured over a range of VPD when plants were growing at 25 or 30 degrees C, and
      again after an abrupt increase of 5 degrees C. In G. max, a restriction of TR
      became evident as VPD increased above 2.0 kPa when temperature was near its
      growth optimum of 30 degrees C. 'Slow wilting' genotype plant introduction (PI)
      416937 exhibited greater TR control at high VPD compared with Hutcheson, and only
      PI 416937 restrained TR after the shift to 35 degrees C. Three of the four G.
      soja genotypes exhibited control over TR with increasing VPD when grown at 25
      degrees C, which is near their estimated growth optimum. The TR control became
      engaged at lower VPD than in G. max and was retained to differing degrees after a
      shift to 30 degrees C. The TR control systems in G. max and G. soja clearly were
      temperature-sensitive and kinetically definable, and more restrictive in the
      'slow wilting' soybean genotype. For the favorable TR control traits observed in
      G. soja to be useful for soybean breeding in warmer climates, the regulatory
      linkage with lower temperatures must be uncoupled.

PMID- 22989318
TI  - Ballistic thermal conductance of a lab-in-a-TEM made Si nanojunction.
AB  - The thermal conductance of a single silicon nanojunction was measured based on a
      Lab-in-a-TEM (microelectromechanical systems in a transmission electron
      microscope) technique and was found to be at least 2 orders of magnitude larger
      than the ones of long nanowires in the 380-460 K temperature range. The
      predominance of ballistic phonon transport appears as the best hypothesis to
      retrieve quantitative predictions despite the geometrical irregularity of the
      junction. The measurement is based on a MEMS structure including an electrostatic
      actuator that allows producing nanojunctions with the accuracy based on the
      resolution of a transmission electron microscope. The thermal conductance is
      measured by two integrated resistors that are simultaneously heating and
      measuring the local temperatures at the nearest of the nanojunction. The
      considerable thermal conductance of short nanojunctions constitutes a new key
      element in the design of nanosystems and in the understanding of the damaging of
      mechanical micronanocontacts. This conducting behavior is also paving the way for
      the development of nanoscale cooling devices as well as of the recent phononic
      information technology.

PMID- 22989319
TI  - Trait impulsivity in suicide attempters: preliminary study.
AB  - Suicide attempt is a risk factor for suicide. To investigate trait impulsivity
      among suicide attempters, 93 attempters admitted to an emergency department and
      113 healthy controls were evaluated using the Japanese version of the Barratt
      Impulsiveness Scale (BIS-11J). Impulsivity was analyzed in relation to clinical
      data in the attempters. Total BIS-11J, attention impulsiveness, and motor
      impulsiveness scores were significantly higher in the attempters than in the
      controls. Both total BIS-11J and non-planning impulsiveness scores were
      significantly higher in attempters with schizophrenia and other psychotic
      disorders among the diagnostic groups. Control of impulsivity should be
      considered as one of the targets for suicide prevention.

PMID- 22989320
TI  - Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation
      in the rat.
AB  - INTRODUCTION: Soluble guanylate cyclase (sGC) is the receptor for nitric oxide
      (NO) and in pathophysiologic conditions where NO formation or bioavailability is
      impaired, erectile dysfunction (ED) occurs. AIM: The aim of this study was to
      investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic
      and pathophysiologic conditions. METHODS: Increases in intracavernosal pressure
      (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were
      investigated in the anesthetized rat. MAIN OUTCOME MEASURES: Increases in ICP/MAP
      in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543
      with exogenous and endogenously released NO were investigated and the effect of
      the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the
      increase in ICP/MAP in response to ic injection of acetylcholine was
      investigated. RESULTS: The ic injections of BAY 41-8543 increased ICP/MAP and the
      duration of the response. BAY 41-8543 was less potent than sodium nitroprusside
      (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than
      the algebraic sum of responses to either agent alone. Simultaneous ic injection
      of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than
      either intervention alone. Atropine and cavernosal nerve crush injury decreased
      the response to nerve stimulation and ic injection of BAY 41-8543 restored the
      response. CONCLUSION: These data show that BAY 41-8543 has significant erectile
      activity and can synergize with exogenous and endogenously released NO. This
      study shows that atropine and nerve crush attenuate the response to cavernosal
      nerve stimulation and that BAY 41-8543 can restore the response. The results with
      atropine, L-NAME and hexamethonium indicate that the response to ic injection of
      acetylcholine is mediated by muscarinic receptors and the release of NO with no
      significant role for nicotinic receptors. These results suggest that BAY 41-8543
      would be useful in the treatment of ED.

PMID- 22989321
TI  - Patients' perspectives of living with a percutaneous endoscopic gastrostomy
      (PEG).
AB  - BACKGROUND: Since enteral nutrition therapy is the preferred nutritional support
      for dysphagic patients with a range of diagnoses, PEG has become part of
      traditional care. However, enteral nutrition with PEG transfers treatment
      responsibility and activity to the patients and their carers, so the advantages
      should be discussed. The aim of this study was therefore to investigate patients'
      experience of living with a percutaneous endoscopic gastrostomy (PEG) in order to
      increase the understanding of patients' need for support. METHOD: In a
      prospective study at Karolinska University Hospital in Sweden, data were
      collected consecutively at the time of PEG and two months later using a study
      specific questionnaire about each patient's experience of living with a PEG.
      Fishers exact test was used to test for statistically significant difference at
      five per cent level. RESULTS: There were 104 responders (response rate of 70%).
      Women felt more limited in daily activity compared to men (p = 0.004). Older
      patients experienced a more limited ability to influence the number of feeding
      times compared to younger (p = 0.026). Highly educated patients found feeding
      more time-consuming (p = 0.004). Patients with a cancer diagnosis reported that
      the PEG feeding interfered with their oral feeding more than patients with a
      neurological disease (p = 0.009). Patients mostly contacted the PEG outpatient
      clinic with problems regarding their PEG, and were mainly assisted by their
      spouse rather than district nurses. CONCLUSIONS: PEG feeding is time-consuming
      and interferes with daily life. Although 73% was satisfied, patients' experiences
      of living with a PEG may be dependent on age, sex, education and diagnosis.
      Spouses are the main carers for PEG patients at home, and patients prefer to go
      to the PEG outpatient clinic for help if problems occur.

PMID- 22989322
TI  - Viral load and alanine aminotransferase correlate with serologic response in
      chronic hepatitis B patients treated with entecavir.
AB  - BACKGROUND AND AIM: Although entecavir has been shown to have good efficacy and
      low resistance for the treatment of chronic hepatitis B (CHB), factors associated
      with a favorable response remain unknown. METHODS: This was a retrospective,
      multicenter study of 248 treatment-naive hepatitis B e antigen (HBeAg)-positive
      patients (69.4% male; median age, 39.4 years) treated with entecavir for more
      than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints
      were HBeAg loss and/or seroconversion. RESULTS: The median baseline levels of
      alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA were 201 U/L
      (range, 27-2415 U/L) and 7.6 log(10) IU/mL (range, 2.2-13.18), respectively. The
      median treatment period was 25.3 months (range, 12-69.6). The rates of ALT
      normalization at years 1, 2, and 3 were 83.1%, 87.9%, and 94.9%, respectively.
      The cumulative rates of HBeAg loss at years 1, 2, and 3 were 20.3%, 38.0%, and
      48.9%, respectively. The rates of undetectable HBV-DNA at years 1, 2, and 3 were
      52.1%, 78.9%, and 82.5%, respectively. Using Cox proportional hazards model,
      multivariate analysis showed that baseline ALT greater than five times the upper
      limit of normal, and viral load were independent factors associated with HBeAg
      loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062-3.085; 0.7
      0.942, respectively). CONCLUSION: Entecavir treatment for 3 years can achieve
      good biochemical and virologic responses in HBeAg-positive CHB patients, but has
      a modest effect on HBeAg loss and/or seroconversion. In addition, baseline serum
      ALT and HBV-DNA levels are independent factors associated with favorable
      treatment responses.

PMID- 22989323
TI  - Nurse practice environment, workload, burnout, job outcomes, and quality of care
      in psychiatric hospitals: a structural equation model approach.
AB  - AIM: To study the relationships between nurse practice environment, workload,
      burnout, job outcomes and nurse-reported quality of care in psychiatric hospital
      staff. BACKGROUND: Nurses' practice environments in general hospitals have been
      extensively investigated. Potential variations across practice settings, for
      instance in psychiatric hospitals, have been much less studied. DESIGN: A cross
      sectional design with a survey. METHOD: A structural equation model previously
      tested in acute hospitals was evaluated using survey data from a sample of 357
      registered nurses, licensed practical nurses, and non-registered caregivers from
      two psychiatric hospitals in Belgium between December 2010-April 2011. The model
      included paths between practice environment dimensions and outcome variables,
      with burnout in a mediating position. A workload measure was also tested as a
      potential mediator between the practice environment and outcome variables.
      RESULTS: An improved model, slightly modified from the one validated earlier in
      samples of acute care nurses, was confirmed. This model explained 50% and 38% of
      the variance in job outcomes and nurse-reported quality of care respectively. In
      addition, workload was found to play a mediating role in accounting for job
      outcomes and significantly improved a model that ultimately explained 60% of the
      variance in these variables. CONCLUSION: In psychiatric hospitals as in general
      hospitals, nurse-physician relationship and other organizational dimensions such
      as nursing and hospital management were closely associated with perceptions of
      workload and with burnout and job satisfaction, turnover intentions, and nurse
      reported quality of care. Mechanisms linking key variables and differences across
      settings in these relationships merit attention by managers and researchers.

PMID- 22989324
TI  - Mitoplasticity: adaptation biology of the mitochondrion to the cellular redox
      state in physiology and carcinogenesis.
AB  - Adaptation and transformation biology of the mitochondrion to redox status is an
      emerging domain of physiology and pathophysiology. Mitochondrial adaptations
      occur in response to accidental changes in cellular energy demand or supply while
      mitochondrial transformations are a part of greater program of cell
      metamorphosis. The possible role of mitochondrial adaptations and transformations
      in pathogenesis remains unexplored, and it has become critical to decipher the
      stimuli and the underlying molecular pathways. Immediate activation of
      mitochondrial function was described during acute exercise, respiratory chain
      injury, Endoplasmic Reticulum stress, genotoxic stress, or environmental toxic
      insults. Delayed adaptations of mitochondrial form, composition, and functions
      were evidenced for persistent changes in redox status as observed in endurance
      training, in fibroblasts grown in presence of respiratory chain inhibitors or in
      absence of glucose, in the smooth muscle of patients with severe asthma, or in
      the skeletal muscle of patients with a mitochondrial disease. Besides,
      mitochondrial transformations were observed in the course of human cell
      differentiation, during immune response activation, or in cells undergoing
      carcinogenesis. Little is known on the signals and downstream pathways that
      govern mitochondrial adaptations and transformations. Few adaptative loops,
      including redox sensors, kinases, and transcription factors were deciphered, but
      their implication in physiology and pathology remains elusive. Mitoplasticity
      could play a protective role against aging, diabetes, cancer, or
      neurodegenerative diseases. Research on adaptation and transformation could allow
      the design of innovative therapies, notably in cancer.

PMID- 22989326
TI  - Effects of a 15-week accumulated brisk walking programme on the body composition
      of primary school children.
AB  - The purpose of this study was to establish whether an accumulated brisk walking
      programme, performed during the school day, is effective in changing body
      composition in primary school children aged 5-11 years. Altogether, 152
      participants (79 boys and 73 girls) took part in this repeated-measures
      intervention study, divided into groups of walkers and controls. The walkers took
      part in the intervention during school time, which involved brisk walking around
      the school grounds for 15 min in the morning and afternoon, at least three times
      a week for 15 weeks. This represented an additional 90 min of moderate physical
      activity per week. The controls undertook their usual school day activities. Pre-
      and post-intervention anthropometric and body composition measures were taken.
      Body fat (-1.95 +/- 2.6%) and fat mass (-0.49 +/- 1.0 kg) were significantly
      reduced in the walkers after the intervention, whereas the controls showed no
      significant changes in these measures. Our results show that regular accumulated
      bouts of brisk walking during the school day can positively affect body
      composition in primary school children.

PMID- 22989327
TI  - Multicenter validation of scoring system of pre-transplant serum ferritin and
      disease risk in patients with acute myeloid leukemia and myelodysplastic syndrome
      after allogeneic hematopoietic stem cell transplant.

PMID- 22989328
TI  - Role of ionic liquid on the conformational dynamics in the native, molten
      globule, and unfolded states of cytochrome c: a fluorescence correlation
      spectroscopy study.
AB  - The role of a room temperature ionic liquid (RTIL, [pmim][Br]) on the size and
      conformational dynamics of a protein, horse heart cytochrome c (Cyt C) in its
      native, molten globule (MG-I and II), and unfolded states is studied using
      fluorescence correlation spectroscopy (FCS). For this purpose, the protein was
      covalently labeled by a fluorescent dye, Alexa Fluor 488. It is observed that the
      addition of the RTIL leads to an increase in the hydrodynamic radius (r(H)) of
      the protein, Cyt C in the native or MG-I state. In contrast, the addition of RTIL
      causes a decrease in the size (hydrodynamic radius, r(H)) of Cyt C unfolded by
      GdnHCl or MG-II state. The decrease in size indicates the formation of a
      relatively compact structure. We detected two types of conformational relaxation
      of the protein. The shorter relaxation time component (~3-5.5 MUs) corresponds to
      the protein folding or intrachain contact formation, while the relatively longer
      time component (~63-122 MUs) may be assigned to the motion of the protein side
      chains or concerted chain dynamics. The burst integrated fluorescence lifetime
      histograms indicate that the increase in size of the protein is accompanied by an
      increase in the contribution of the shorter component (~0.3-0.4 ns) with a
      concomitant decrease of the contribution of the longer component (~2.8-3.6 ns).
      An opposite trend is observed during the decrease in size of the protein.

PMID- 22989329
TI  - Evaluation of insulin expression and secretion in genetically engineered gut K
      and L-cells.
AB  - BACKGROUND: Gene therapy could provide an effective treatment of diabetes.
      Previous studies have investigated the potential for several cell and tissue
      types to produce mature and active insulin. Gut K and L-cells could be potential
      candidate hosts for gene therapy because of their special features. RESULTS: In
      this study, we isolated gut K and L-cells to compare the potential of both cell
      types to produce insulin when exposed to similar conditions. The isolated pure K
      and L-cells were transfected with recombinant plasmids encoding insulin and with
      specific promoters for K or L-cells. Insulin expression was studied in response
      to glucose or meat hydrolysate. We found that glucose and meat hydrolysate
      efficiently induced insulin secretion from K and L-cells. However, the effects of
      meat hydrolysate on insulin secretion were more potent in both cells compared
      with glucose. Results of enzyme-linked immunosorbent assays showed that L-cells
      secreted more insulin compared with K-cells regardless of the stimulator,
      although this difference was not statistically significant. CONCLUSION: The
      responses of K and L-cells to stimulation with glucose or meat hydrolysate were
      generally comparable. Therefore, both K and L-cells show similar potential to be
      used as surrogate cells for insulin gene expression in vitro. The potential use
      of these cells for diabetic gene therapy warrants further investigation.

PMID- 22989325
TI  - Low-level laser therapy regulates microglial function through Src-mediated
      signaling pathways: implications for neurodegenerative diseases.
AB  - BACKGROUND: Activated microglial cells are an important pathological component in
      brains of patients with neurodegenerative diseases. The purpose of this study was
      to investigate the effect of He-Ne (632.8 nm, 64.6 mW/cm2) low-level laser
      therapy (LLLT), a non-damaging physical therapy, on activated microglia, and the
      subsequent signaling events of LLLT-induced neuroprotective effects and
      phagocytic responses. METHODS: To model microglial activation, we treated the
      microglial BV2 cells with lipopolysaccharide (LPS). For the LLLT-induced
      neuroprotective study, neuronal cells with activated microglial cells in a
      TranswellTM cell-culture system were used. For the phagocytosis study,
      fluorescence-labeled microspheres were added into the treated microglial cells to
      confirm the role of LLLT. RESULTS: Our results showed that LLLT (20 J/cm2) could
      attenuate toll-like receptor (TLR)-mediated proinflammatory responses in
      microglia, characterized by down-regulation of proinflammatory cytokine
      expression and nitric oxide (NO) production. LLLT-triggered TLR signaling
      inhibition was achieved by activating tyrosine kinases Src and Syk, which led to
      MyD88 tyrosine phosphorylation, thus impairing MyD88-dependent proinflammatory
      signaling cascade. In addition, we found that Src activation could enhance Rac1
      activity and F-actin accumulation that typify microglial phagocytic activity. We
      also found that Src/PI3K/Akt inhibitors prevented LLLT-stimulated Akt (Ser473 and
      Thr308) phosphorylation and blocked Rac1 activity and actin-based microglial
      phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway.
      CONCLUSIONS: The present study underlines the importance of Src in suppressing
      inflammation and enhancing microglial phagocytic function in activated microglia
      during LLLT stimulation. We have identified a new and important neuroprotective
      signaling pathway that consists of regulation of microglial phagocytosis and
      inflammation under LLLT treatment. Our research may provide a feasible
      therapeutic approach to control the progression of neurodegenerative diseases.

PMID- 22989331
TI  - Rhodium-catalyzed cascade oxidative annulation leading to substituted naphtho[1,8
      bc]pyrans by sequential cleavage of C(sp2)-H/C(sp3)-H and C(sp2)-H/O-H bonds.
AB  - The cascade oxidative annulation reactions of benzoylacetonitrile with internal
      alkynes proceed efficiently in the presence of a rhodium catalyst and a copper
      oxidant to give substituted naphtho[1,8-bc]pyrans by sequential cleavage of
      C(sp(2))-H/C(sp(3))-H and C(sp(2))-H/O-H bonds. These cascade reactions are
      highly regioselective with unsymmetrical alkynes. Experiments reveal that the
      first-step reaction proceeds by sequential cleavage of C(sp(2))-H/C(sp(3))-H
      bonds and annulation with alkynes, leading to 1-naphthols as the intermediate
      products. Subsequently, 1-naphthols react with alkynes by cleavage of C(sp(2))
      H/O-H bonds, affording the 1:2 coupling products. Moreover, some of the
      naphtho[1,8-bc]pyran products exhibit intense fluorescence in the solid state.

PMID- 22989330
TI  - Cardiac surgery versus stenting: what is better for the patient?
AB  - Patterns of myocardial revascularization have changed significantly over the past
      decade. There has been a relative decrease of coronary artery bypass grafting
      (CABG) compared with percutaneous coronary intervention (PCI) and some patients
      are undergoing PCI for coronary lesions traditionally reserved for CABG. The mid-
      to long-term results of several trials comparing PCI with CABG have recently been
      published. For three-vessel disease, CABG is superior to PCI, with lower rates of
      major adverse cardiac events. PCI may be equivalent to CABG for three-vessel
      disease in the lowest disease complexity tercile (SYNTAX score <22; ~20% of
      patients). This review focuses on the most recent evidence for myocardial
      revascularization in patients with multi-vessel and left main coronary artery
      disease.

PMID- 22989332
TI  - 127I and 129I species and transformation in the Baltic proper, Kattegat, and
      Skagerrak basins.
AB  - Occurrence of anthropogenic (129)I in seawater has provided invaluable
      information about water circulation and exchange rates, but results on (129)I
      species (iodide and iodate) are limited and only available for surface water. We
      here present the first extensive results on (129)I and (127)I species in samples
      of seawater depth profiles, which were collected in August 2006 and April 2007 in
      the Skagerrak, Kattegat, and Baltic Proper. The results expose <=10% annual
      reduction of iodate as (129)I is transported from the English Channel along the
      Dutch coast and German Bight into the Skagerrak and Kattegat. The results also
      suggest strong variability between surface and bottom seawater with respect to
      the predominant iodine species. Distribution of iodide and iodate of both (127)I
      and (129)I in the Kattegat mainly reflects water mixing process rather than
      speciation transformation. In water of the Baltic Proper, high (127)I(
      )/(127)IO(3)(-) and (129)I(-)/(129)IO(3)(-) values suggest effective reduction of
      iodate with a maximum rate of 8 * 10(-7) ((127)IO(3)(-)) and 6 * 10(-14)
      ((129)IO(3)(-)) (g/m(3).day). The reduction process of iodate seems to be related
      to decomposition of organic matter and photochemically induced reactions.

PMID- 22989334
TI  - In-111 transferrin scintigraphy in cirrhosis with hypoalbuminemia: evidence for
      protein-losing enteropathy in a small group of selected cases.
AB  - BACKGROUND: Hypoalbuminemia commonly observed in cirrhosis is considered to be
      mainly related to hepatocellular dysfunction. However, the correlation between
      the decrease in serum albumin and liver function is far from linear and arguments
      in favor of an additive role of protein-losing enteropathy have been brought by a
      few studies. AIM: To assess the potential role of protein-losing enteropathy in a
      group of patients with cirrhosis, portal hypertension, and hypoalbuminemia.
      DESIGN AND METHODS: Eleven patients with documented cirrhosis, portal
      hypertension, and a low serum albumin level compared to liver function underwent
      an (111)In-transferrin scintigraphy. RESULTS: Using this sensitive method of
      investigation, nine exhibited features suggestive of exudative enteropathy. Serum
      albumin level and digestive protein loss were even correlated (Pearson's
      coefficient = -0.529, one-sided p = 0.047). Protein loss were however not
      correlated with the degree of portal hypertension or with the extent of liver
      dysfunction evaluated by the aminopyrine breath test. CONCLUSIONS: Our
      preliminary data obtained in a small group of selected patients with cirrhosis,
      portal hypertension, and hypoalbuminemia indicate that protein-losing enteropathy
      may represent an appreciable and underestimated cause of hypoproteinemia.

PMID- 22989333
TI  - Design and validation of bicyclic iminopyrimidinones as beta amyloid cleaving
      enzyme-1 (BACE1) inhibitors: conformational constraint to favor a bioactive
      conformation.
AB  - On the basis of our observation that the biaryl substituent of iminopyrimidinone
      7 must be in a pseudoaxial conformation to occupy the contiguous S1-S3 subsites
      of BACE1, we have designed a novel fused bicyclic iminopyrimidinone scaffold
      intended to favor this bioactive conformation. Strategic incorporation of a
      nitrogen atom in the new constrained ring allowed us to develop SAR around the
      S2' binding pocket and ultimately resulted in analogues with low nanomolar
      potency for BACE1. In particular, optimization of the prime side substituent led
      to major improvements in potency by displacement of two conserved water molecules
      from a region near S2'. Further optimization of the pharmacokinetic properties of
      this fused pyrrolidine series, in conjunction with facile access to a rat
      pharmacodynamic model, led to identification of compound 43, which is an orally
      active, brain penetrant inhibitor that reduces Abeta(40) in the plasma, CSF, and
      cortex of rats in a dose-dependent manner.

PMID- 22989335
TI  - Is hemiepiphytism an adaptation to high irradiance? Testing seedling responses to
      light levels and drought in hemiepiphytic and non-hemiepiphytic Ficus.
AB  - The epiphytic growth habit in many Ficus species during their juvenile stages has
      commonly been hypothesized to be an adaptation for avoiding deep shade in the
      forest understory, but this has never been tested experimentally. We examined
      growth and ecophysiology in seedlings of three hemiepiphytic (Hs) and three non
      hemiepiphytic (NHs) Ficus species grown under different irradiance levels. Both
      Hs and NHs exhibited characteristics of high light requiring species, such as
      high plasticity to growth irradiance and relatively high maximum photosynthetic
      assimilation rates. Diurnal measurements of leaf gas exchange showed that Hs have
      much shorter active photosynthetic periods than NHs; moreover, leaves of Hs have
      lower xylem hydraulic conductivity but stronger drought tolerance as indicated by
      much lower rates of leaf diebacks during the drought treatment. Seedlings of NHs
      had 3.3- and 13.3-fold greater height and biomass than those of Hs species after
      growing in the nursery for 5 months, indicating a trade-off between growth and
      drought tolerance due to the conflicting requirements for xylem conductivity and
      cavitation resistance. This study does not support the shade-avoidance
      hypothesis; rather, it suggests that the canopy regeneration in Hs is an
      adaptation to avoid alternative terrestrial growth-related risks imposed to tiny
      Ficus seedlings. The NHs with terrestrial regeneration reduce these risks by
      having an initial burst of growth to rapidly gain relatively large seedling
      sizes, while in Hs seedlings more conservative water use and greater drought
      tolerance for surviving the canopy environment are intrinsically associated with
      slow growth.

PMID- 22989336
TI  - Recombinant hybrids retain heterozygosity at many loci: new insights into the
      genomics of reproductive isolation in Populus.
AB  - The maintenance of species barriers in the face of gene flow is often thought to
      result from strong selection against intermediate genotypes, thereby preserving
      genetic differentiation. Most speciation genomic studies thus aim to identify
      exceptionally divergent loci between populations, but divergence will be affected
      by many processes other than reproductive isolation (RI) and speciation. Through
      genomic studies of recombinant hybrids sampled in the wild, genetic variation
      associated with RI can be observed in situ, because selection against
      incompatible genotypes will leave detectable patterns of variation in the hybrid
      genomes. To better understand the mechanisms directly involved in RI, we
      investigated three natural 'replicate' hybrid zones between two divergent Populus
      species via locus-specific patterns of ancestry across recombinant hybrid
      genomes. As expected, genomic patterns in hybrids and their parental species were
      consistent with the presence of underdominant selection at several genomic
      regions. Surprisingly, many loci displayed greatly increased between-species
      heterozygosity in recombinant hybrids despite striking genetic differentiation
      between the parental genomes, the opposite of what would be expected with
      selection against intermediate genotypes. Only a limited, reproducible set of
      genotypic combinations was present in hybrid genomes across localities. In the
      absence of clearly delimited 'hybrid habitats', our results suggest that complex
      epistatic interactions within genomes play an important role in advanced stages
      of RI between these ecologically divergent forest trees. This calls for more
      genomic studies that test for unusual patterns of genomic ancestry in hybridizing
      species.

PMID- 22989337
TI  - Protocol for vastly reduced emesis after strabismus surgerg.

PMID- 22989338
TI  - Words: Perception, "-Omics" Another Epidemic? Vaccine Optic Neuritis; An
      Amblyopia Symposium; Strasbismus surgery anesthesia.

PMID- 22989339
TI  - Reversible blindness in bilateral optic neruritis associated with nasal flu
      vaccine.
AB  - BACKGROUND: Various case reports have shown possible associations between optic
      neuritis and different vaccines.  Some of the vaccines include influenza,
      hepatitis B and anthrax PURPOSE: To present evidence for a causal relationship
      between optic neuritis and Live Attenuated Influenza Vaccine (LAIV), administered
      as nasal flu vaccine. METHODS: Case Report.  In a 13-year-old male with bilateral
      optic neuritis, detailed clinical history, neuro-ophthalmologic examination,
      magnetic resonance imaging, stereo-disc photos, visual field testing, ocular
      coherence tomography, blood tests and cerebral spinal fluid analysis were
      performed. RESULTS: Exam findings on presentation:  BCVA: 20/CF OD; 20/LP OS. 
      Positive relative afferent pupil defect OD.  Unremarkable anterior segment and
      posterior segment exam.  No papillitis or papilledema. Global visual field defect
      OU based on Humphrey 30-2.  MRI: diffuse enlargement of Optic Chiasm with
      inflammation of distal optic nerves bilateral.  Blood cultures and CSF were
      negative. Patient received 3 divided doses of methyl prednisone with mild
      improvement of vision upon hospital discharge and marked improvement of vision at
      2 month follow up. CONCLUSION: In this child, no infectious, vascular,
      granulomatous, viral or immune-related cause of optic neuritis was identified.
      This case provides compelling evidence that supports the nasal flu vaccination as
      a cause of optic neuritis.

PMID- 22989340
TI  - Characterization of bangerter filter effect in mild and moderate amblyopia
      associated with strabismus.
AB  - BACKGROUND: To evaluate the outcome achieved by using Bangerter filters in cases
      of mild to moderate amblyopia associated to strabismus. METHODS: Prospective
      study comprising 30 children (age range 2-9 years) with unilateral mild to
      moderate amblyopia associated to esotropia and hyperopia. All patients were
      treated by prescribing the use of a Bangerter filter in the non-amblyopic eye in
      combination with the refractive correction. In all cases, the filter selected
      induced a reduction of the visual acuity of 2 lines below the best spectacle
      corrected visual acuity (BSCVA) of the amblyopic eye. A follow-up of 12 months
      was completed. RESULTS: A statistically significant improvement in BSCVA was
      observed at 3 months in amblyopic eyes (p 0.01), with additional significant
      improvements at 6, 9 and 12 months (p 0.02). The BSCVA in non-amblyopic eyes
      remained unchanged during the initial 6 months of treatment (p 0.52), with a
      significant improvement at 9 months (p=0.03). Significant differences between
      amblyopic and fellow eyes were only detected at 3 months (p 0.01). Filter density
      had to be changed during the follow-up in 12 eyes (40%). Inverse significant
      correlations between baseline filter density and BSCVA were found at the end of
      the follow-up (r -0.35, p 0.01). A significant correlation of the visual acuity
      with the baseline visual acuity difference among eyes was only present at 3
      months (r=-0.55, p 0.01). CONCLUSIONS: Bangerter filters seem to be useful for
      treating mild or moderate amblyopia due to strabismus, but ocular dominance
      inversion should be maintained during treatment for obtaining an optimized
      outcome.

PMID- 22989341
TI  - Depth of suppression in anisometropic amblyopia (with or without microtropia).
AB  - BACKGROUND AND PURPOSE: There are conflicting reports concerning the relationship
      between depth of suppression and  level of amblyopia in strabismics. Little
      attention has been given to anisometropes. This study examines the density of
      suppression in anisometropic amblyopes, with or without microtropia, and
      investigates whether there is a relationship with level of amblyopia. METHODS:
      Patients with anisometropia (defined as a difference of 1D or 0.5 D cyl),
      binocular single vision and a difference in corrected visual acuity of at least
      0.1 logMAR between eyes were recalled. The degree of amblyopia was expressed as
      the interocular difference using the Bailey-Lovie logMAR chart. Stereoacuity
      (Titmus test), binocular alignment and fixation were recorded. The depth of
      suppression was measured using the neutral density filter bar together with the
      Worth four dot test at 4.5m (subtending an angle of 0.5 degrees). Best spherical
      equivalent (BSE) was calculated to represent anisometropia. RESULTS: Thirteen
      participants aged 8.3 years to 12.1 years (mean 9.7 years) completed the study. 
      No significant correlation was present (r=0.10, p=0.74) between the depth of
      suppression and degree of amblyopia.  However, there was a correlation between
      depth of suppression and level of stereoacuity (r=0.59, p=0.03). Six participants
      had microtropia and showed stronger suppression (p=0.03) and worse stereoacuity
      (p=0.001) than the pure anisometropes. CONCLUSIONS: No evidence was found of a
      relationship between density of suppression and amblyopia in this cohort of
      anisometropic amblyopes.

PMID- 22989342
TI  - Frequent Evaluation To Improve Compliance In Patients Treated With Occlusion For
      Amblyopia: A Randomized controlled Trial.
AB  - BACKGROUND: The benefits of occlusion treatment for amblyopia are well
      established.True compliance can be difficult to assess and is usually based on
      patient history. We hypothesize that more visits to the physician provides more
      chances to improve compliance. METHODS: We conducted a prospective, comparative,
      blind trial in which 30 children with amblyopia were randomly assigned to be
      followed up more frequently (every 4 to 6 weeks) (study group) or as established
      on our standard  regular basis (month intervals based on age in years) (control
      group). The primary outcome was to study differences in treatment compliance
      between these groups. The secondary outcome was to report compliance in a group
      of Chilean children and to compare survey results with adherence, to assess
      concordance between them. RESULTS: Baseline clinical characteristics were similar
      in the two groups. 30 patients were recruited. Mean compliance for all patients
      was 82%. Study group compliance was 83% versus 76% in control group (p = 0.5).
      Without epidemiology, intention to treat analysis (ITT), study group compliance
      was 97% compared to 76%  in control group (p = 0.049). Pearson correlation
      between negative responses to a parental survey after treatment, of the
      percentage of adherence and compliance, was -0.57 and statistically significant
      (p = 0.013). CONCLUSIONS: There were no differences in patient compliance
      comparing more frequent evaluation versus a follow up evaluation based in an age
      according scheme. There is a high compliance to occlusion therapy in this group
      of Chilean children. If parents reported more negative adherence aspects in the
      survey, the worse the compliance.

PMID- 22989343
TI  - Stereo Perception: A Conscious Experience: Perception Is "In" and Big In BV Via
      The Egocenter.

PMID- 22989344
TI  - Quality of life and its associated factors among patients with two common types
      of chronic mental illness living in Kaohsiung City.
AB  - AIM: This study explored the associations of personal, disease, family, and
      social factors with quality of life (QoL) in patients with two common types of
      chronic mental illness (CMI) living in Kaohsiung City, Taiwan. METHODS: Using a
      convenience sample and a cross-sectional design, 714 patients (50.1% male, 49.9%
      female) with CMI (72.1% schizophrenia and 27.9% affective disorder) and their
      caregivers were recruited. Demographic information was collected via the
      following questionnaires: 12-Item Short-Form Health Survey (SF-12), five-item
      Brief Symptom Rating Scale (BSRS-5), Caregiver Burden Scale, and Clinical Global
      Impressions (CGI-S) Scale. Pearson correlations and hierarchical regression
      analyses were used to predict QoL. RESULTS: Disease factors accounted for 17-50%
      of the change in variance. Predictors of low mental subscale scores included the
      following: high psychological distress and high family burden as well as a
      history of suicide attempts, negative caregiver attitudes, and living away from
      home. Disease factors also explained the greatest variance in the physical
      subscales. Predictors of low physical subscale scores included the following:
      high psychological distress, age, unemployment, a history of suicide attempts,
      high family burden, and living alone. CONCLUSIONS: Disease factors were the most
      important predictors of QoL in patients with CMI. Family factors were more
      important than social factors on the mental subscales. Differential relationships
      were also found for the other two dimensions. Together, these results indicate
      that a wide range of factors improve the QoL in patients with CMI.

PMID- 22989345
TI  - Crystallinity segregation upon selective self-assembling of gold colloidal single
      nanocrystals.
AB  - Spontaneous separation of single from polycrystalline 5 nm gold nanocrystals
      (NCs) is observed in colloidal solution. This segregation takes place upon self
      assembling of single crystalline NCs at the air-solvent interface and in
      precipitated superlattices. Polycrystalline NCs are observed to remain in the
      suspension. Transmission electron microscopy analysis of the size distribution of
      NCs issued from the different populations indicates that the NC size does not
      change from each other, excluding therefore any size segregation in this process.
      Using both low-frequency Raman scattering and X-ray diffraction provides reliable
      characterization of nanocrystallinity for each population of NCs, thus confirming
      the crystallinity segregation. The single crystalline NCs are found by electron
      diffraction to self-assemble into close-packed superlattices with long-range
      translational and orientational ordering, while polycrystalline NCs behave like
      spheres with no preferential orientation. The face-to-face orientational
      ordering, which is only observed for single crystalline NCs, supports the
      relevance of the specific crystallinity-related morphologies of these NCs in
      their better ability to self-assemble. Exploiting this spontaneous segregation
      would open up a simple alternative to other demanding routes for controlling
      crystallinity of nanocrystals and optimizing their properties for potential
      applications.

PMID- 22989346
TI  - Fulminant invasive aspergillosis of the mediastinum in an immunocompetent host: a
      case report.
AB  - INTRODUCTION: Invasive aspergillosis is a serious complication in
      immunocompromised patients. It is an opportunistic disease, which predominantly
      occurs in the lungs, although dissemination to virtually any organ is possible.
      Invasive aspergillosis in an immunocompetent patient with extension to the
      mediastinum has rarely been reported. Here, we present the case of a patient with
      no apparent immunodeficiency state, who presented with Aspergillus endocarditis
      and fulminant invasive aspergillosis with extensive involvement of the
      mediastinal structures, which ultimately was responsible for her death. To the
      best of our knowledge, this is the first reported case in the literature on
      fulminant invasive mediastinal aspergillosis with extension to the pulmonary
      vasculature and concomitant Aspergillus endocarditis in an apparently
      immunocompetent patient without pre-existing lung disease. CASE PRESENTATION: Our
      patient was a previously healthy 47-year-old Asian woman, who presented to our
      emergency room with severe progressive shortness of breath of one month's
      duration, associated with orthopnea and unstable vital signs. CONCLUSION:
      Invasive aspergillosis has been described in the presence of pulmonary disease,
      such as chronic obstructive pulmonary disorder, and one case has been reported in
      a patient without preexistent disease, but none of these have been fatal. Our
      case is therefore the first reported case of its kind. Our case shows that
      fulminant aspergillosis can occur in an immunocompetent host and can be fatal. We
      conclude that invasive aspergillosis should not be excluded from the differential
      diagnosis on the basis of immunocompetency.

PMID- 22989347
TI  - Encapsulating nanoemulsions inside eLiposomes for ultrasonic drug delivery.
AB  - An eLiposome is a liposome encapsulating an emulsion nanodroplet and can be used
      for drug delivery. For example, therapeutic agents are encapsulated inside the
      eLiposomes, and the application of ultrasound can cause the emulsion droplet to
      change from liquid to gas, thus increasing the volume inside the vesicle and
      causing rupture and the release of the drug. In this research, two different
      methods were used to prepare eLiposomes. In the first method, emulsion droplets
      were made of perfluorohexane or perfluoropentane and stabilized with 1,2
      dipalmitoyl-sn-glycero-3-phosphate. A layer of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine was dried in a round-bottomed flask. Then the emulsion suspension
      was added to the flask. As the suspension hydrated the phospholipids, they formed
      liposomes around the emulsions. In the second method, emulsions and liposomes
      were made separately, and then they were mixed using ultrasound. The advantage of
      this second method compared to the previous one is that eLiposomes can be made
      with fewer restrictions because of incompatible combinations of surfactants.
      Dynamic light scattering and transmission electron microscopy were used to
      measure the size of the emulsions, liposomes, and eLiposomes. The size of
      eLiposomes is appropriate for extravasation into tumors with malformed capillary
      beds. We hypothesize that ultrasound breaks open these eLiposomes. Both types of
      eLiposomes were constructed with folate attached via a poly(ethylene glycol)
      tether to induce endocytosis of the eLiposome. The latter eLiposomes were
      successfully used to deliver calcein as a model drug to HeLa cells.

PMID- 22989348
TI  - alpha1-blocker tamsulosin as initial treatment for patients with benign prostatic
      hyperplasia: 5-year outcome analysis of a prospective multicenter study.
AB  - OBJECTIVE: To comprehensively analyze the 5-year outcomes of tamsulosin treatment
      for patients with benign prostatic hyperplasia. METHODS: Tamsulosin (0.2 mg/day)
      was given to 112 patients who had International Prostate Symptom Scores >=8. They
      were prospectively followed for 5 years with periodic evaluation. If tamsulosin
      had to be discontinued, the reason was determined. Treatment failure was
      considered in the case of disease progression (postvoid residual urine volume
      >=200 mL, acute urinary retention, febrile urinary tract infection or
      hydronephrosis as a result of bladder outlet obstruction), conversion to other
      alpha1-blockers or need for surgery. An intention-to-treat analysis was carried
      out. RESULTS: A total of 34 patients (30.4%) continued the same medication for
      the overall study period, whereas 78 patients (69.6%) discontinued the
      medication. International Prostate Symptom Scores, Benign Prostatic Hyperplasia
      Problem Index and Quality of Life Index were significantly improved over the 5
      year period. Treatment failure was observed in 21 patients (18.8%). Baseline
      prostate volume and postvoid residual urine volume were independent factors to
      predicting treatment failure. A total of 21 patients (18.8%) discontinued
      tamsulosin because of an improvement of symptoms. They were younger and had lower
      prostate-specific antigen levels than the remaining 91 patients. Their symptoms
      were stable even 1 year after termination of therapy. CONCLUSIONS: Long-term
      efficacy of tamsulosin was observed, although only a small portion of patients
      continued the treatment. alpha1-blocker monotherapy might be not appropriate for
      achieving a good long-term outcome in patients with a large prostate volume and a
      large amount of postvoid residual urine volume. Persistent improvement of
      symptoms, even after termination of tamsulosin, was observed in young patients
      with low prostate-specific antigen levels.

PMID- 22989349
TI  - Antibacterial resistances in uncomplicated urinary tract infections in women:
      ECO.SENS II data from primary health care in Austria.
AB  - BACKGROUND: Uncomplicated urinary tract infections (UTI) are a frequent reason
      for consultation of women in primary health care. To avoid therapy failure and
      development of resistances, the choice of an antibiotic should be based on the
      knowledge of recent local resistance data but these data are scarce for the
      Austrian primary health care sector. Within the context of the ECO.SENS II study
      it was the aim to obtain appropriate and relevant local resistance data and
      describe the changes in the resistance pattern in comparison to the ECO.SENS
      study. METHODS: 23 GPs from different parts of Austria participated in the study
      between July 2007 and November 2008. According to the defined inclusion- and
      exclusion criteria female patients with symptoms of an uncomplicated UTI were
      included and a midstream urine sample was collected. In case of significant
      bacteriuria susceptibility testing of E. coli against 14 antibiotics was
      performed. Descriptive statistical methods were used. RESULTS: In 313 patients
      included in the study, a total of 147 E. coli isolates (47%) were detected and
      tested. The resistance rates were in %: Mecillinam (0.0), nitrofurantoin (0.7),
      fosfomycin trometamol (0.7), gentamycin (1.4), cefotaxime (2.7), ceftazidime
      (2.7), Cephadroxil (4.1) and ciprofloxacin (4.1). Higher resistance rates were
      found in amoxicillin/clavulanic acid (8.9), nalidixic acid (9.6),
      trimethoprim/sulphamethoxazole (14.4), trimethoprim (15.8), sulphamethoxazole
      (21.2) and ampicillin (28.8). Additionally, the comparison of these results with
      the results of the ECO.SENS study demonstrated an increase in resistance rates of
      ampicillin, amoxicillin/clavulanic acid, nalidixic acid and ciprofloxacin.
      CONCLUSIONS: The resistance data for E. coli in uncomplicated UTIs in women
      gained by this study are the most recent data for this disease in Austria at the
      moment. The increased resistance rates of amoxicillin/clavulanic acid,
      ciprofloxacin and nalidixic acid should be respected when choosing an appropriate
      antibiotic for uncomplicated UTIs. The use of ampicillin, sulphamethoxazole,
      trimethoprim and trimethoprim/sulphametoxazole in uncomplicated UTIs in women
      should be questioned at all. The findings of this study should result in a
      regular surveillance system of resistances emerging in the ambulatory sector
      designed after the model of the EARS-Net.

PMID- 22989350
TI  - Are visiting oncologists enough? A qualitative study of the needs of Australian
      rural and regional cancer patients, carers and health professionals.
AB  - AIM: Survival rates for patients with cancer who live in rural and regional areas
      are worse than in metropolitan areas. This may be due to geographical isolation,
      delayed diagnosis, inadequate transport, lower socioeconomic status and workforce
      shortages. We conducted a qualitative study of rural patients, carers and health
      professionals. It aimed to identify concerns about, and strategies to optimize
      cancer care from those with direct experience. METHODS: Focus groups and
      structured interviews were conducted in New South Wales, Australia at four rural
      and regional hospitals (Bega, Dubbo, Tamworth and Albury) and three metropolitan
      locations (in Sydney and the Jean Colvin Hostel) caring for rural patients.
      Sessions were audiotaped, transcribed and analyzed using thematic analysis.
      RESULTS: In total, 36 patients, 14 carers and 32 health professionals were
      interviewed in seven focus groups and 42 individual interviews. Concerns related
      to access to oncologists and other health professionals, and for services for
      investigation and treatment, the financial and social consequences of travel,
      unmet carer support needs and the hardships for health professionals. Strategies
      for improvement included comprehensive staffing and services coordinated in a hub
      and spoke model from adjacent larger centers, adequate reimbursement for travel
      and better carer support. CONCLUSION: We identified broad concerns about regional
      and rural cancer care in Australia. The Australian Federal Government commitment
      of $560 million to establish regional cancer centers is welcome; however,
      improvements must extend beyond infrastructure funding in large regional centers
      to comprehensive staffing in centers currently lacking resident oncologists,
      travel support and assistance for carers.

PMID- 22989351
TI  - YKL-40-gene polymorphism affects acute cellular rejection and fibrosis
      progression after transplantation for hepatitis C virus-induced liver disease.
AB  - BACKGROUND AND AIM: The development of end-stage graft disease is suspected to be
      partially determined by an individual genetic background. The aim of our study
      was to determine the prevalence of YKL-40-gene polymorphism in hepatitis C virus
      (HCV)-positive patients and its impact on the incidence of acute cellular
      rejection (ACR), graft fibrosis and antiviral treatment response. METHODS: A
      total of 149 patients, who underwent liver transplantation for HCV-induced liver
      disease, were genotyped for YKL-40 (rs4950928; G/C) by TaqMan Genotyping Assay.
      The results were correlated with 616 post-transplant graft biopsies regarding
      inflammation, fibrosis and evidence for ACR. RESULTS: No association of YKL-40
      genotypes was observed regarding mean inflammation grade (P = 0.216) and
      antiviral treatment outcome (P = 0.733). However, the development of advanced
      fibrosis (F3-4) was significantly faster in patients with YKL-40-G-allele: t(CC)
      = 4.6 versus t(CG/GG) = 2.4 years; P = 0.006. Patients with lower fibrosis (F0-2)
      compared to advanced fibrosis (F3-4) received significantly more frequent dual
      immunosuppression (calcineurin inhibitors [CNIs]/mofetile mycophenolate [MMF] vs
      CNIs; P = 0.003). ACR-occurrence was associated with YKL-40-genotypes (ACR: CC =
      60.4%, CG = 25.0% and GG = 14.6% vs non-ACR: CC = 74.2%, CG = 23.8% and GG =
      2.0%; P = 0.009) and with gender compatibility between donor and recipient (P =
      0.012). CONCLUSION: Fibrosis progression and ACR-incidence after transplantation
      for HCV-induced liver disease seem to be under genetic control. The negative
      impact of G-allele on post-transplant events observed in our study, deserves
      attention and should be verified in larger liver transplantation-cohorts.

PMID- 22989352
TI  - Appearance-based interventions to reduce ultraviolet exposure and/or increase sun
      protection intentions and behaviours: a systematic review and meta-analyses.
AB  - OBJECTIVES: A systematic review and meta-analyses were conducted to identify and
      review research examining the impact of appearance-based interventions on sun
      protection intentions and/or ultraviolet (UV) exposure behaviour. METHODS: A
      search of 16 databases including PsycARTICLES, Cochrane Library and Web of
      Knowledge was conducted to identify studies examining the impact of appearance
      based interventions on reducing UV exposure and/or increasing sun protection
      intentions and behaviours. A total of 21 articles met the inclusion criteria, and
      these studies were subjected to a systematic review and meta-analyses to
      determine the effectiveness of the interventions. RESULTS: Interventions used a
      variety of techniques including UV technology and photoaging information. Study
      design and outcome measures varied. The research indicated that appearance-based
      interventions have a positive effect on UV exposure and sun protection intentions
      and behaviour. CONCLUSIONS: Findings suggest that interventions based on the
      appearance-damaging effects of UV exposure, and the positive effects of sun
      protection, may have a role in health promotion. It is concluded that there is a
      need for further research incorporating a wider range of participants, and using
      qualitative and mixed methods designs. STATEMENT OF CONTRIBUTION: What is already
      known on the subject? Recreational exposure to ultraviolet (UV) radiation, are
      the primary causes of all melanomas, leading to skin cancer. A previous
      systematic review (Dodd & Forshaw, ) looking at the efficacy of appearance
      focussed interventions in skin cancer prevention, suggested that there were
      significant effects for UV protection behaviour after such interventions. What
      does this study add? An up-to-date systematic review of studies that has carried
      out appearance-based interventions to reduce UV exposure and/or increase sun
      protection intentions and behaviours. A meta-analysis of data providing
      statistical evidence indicating that appearance-based interventions have a
      positive effect on UV exposure and sun protection intentions and behaviour.

PMID- 22989353
TI  - Effects of statins on oxidative stress and primed polymorphonuclear leukocytes in
      hyperlipidemic patients.
AB  - Inflammation and oxidative stress are among the factors that have been implicated
      in the pathogenesis of hyperlipidemia. In metabolic syndrome and hyperlipidemic
      patients, peripheral polymorphonuclear leukocytes (PMNL) are primed and they
      release uncontrolled superoxide that contributes to oxidative stress and
      inflammation. Recent studies have demonstrated that the anti-hyperlipidemic drug,
      Atrovastatin effects improvement in endothelial function, exhibits anti-oxidative
      characteristics and reduces lipid markers of oxidation. To evaluate possible
      nontraditional effects of treatment with Atrovastatin on PMNL priming, oxidative
      stress and inflammation in hyperlipidemia, 50 non-smoking hyperlipidemic patients
      were treated for 6 months with Atrovastatin and compared to age and gender
      matched healthy controls. PMNL priming was assessed by the rate of superoxide
      release from separated, phorbol ester-stimulated PMNL and by PMNL-CD11b levels.
      Inflammation was reflected by blood inflammatory markers including albumin,
      transferrin, C-reactive protein (CRP) and fibrinogen levels, white blood cells
      (WBC), PMNL counts and PMNL apoptosis. Atrovastatin treatment showed a reduction
      in PMNL priming, PMNL apoptosis, fibrinogen and CRP levels concomitant with
      decreased lipid levels. Atrovastatin may be preferred for hyperlipidemic patients
      owing to its combined anti-PMNL priming and anti-inflammatory effects in addition
      to its anti-atherogenic effects.

PMID- 22989355
TI  - Flow cytometric immunophenotyping of regulatory T cells in chronic lymphocytic
      leukemia: comparative assessment of various markers and use of novel antibody
      panel with CD127 as alternative to transcription factor FoxP3.
AB  - This study analyzed the frequency of regulatory T cells (Tregs) in chronic
      lymphocytic leukemia (CLL) by multiparameter flow cytometric immunophenotyping.
      Patients showed significantly increased frequencies of Tregs as compared to
      controls, a significantly higher percentage than that identified by previous
      studies, possibly indicating a different prognosis of CLL in different parts of
      the world and, more precisely, a worse prognosis of CLL in the Indian population.
      A higher frequency of Tregs was also seen in advanced stage of disease with
      significantly reduced frequencies of Tregs in patients with CLL after
      chemotherapy. A significant proportion of CD127low/-FoxP3+ Tregs expressed only
      low levels of CD25. Thus, CD127 appears to be a better marker than CD25 for the
      identification of CD4+FoxP3+ T cells as potential Tregs. Our results suggest that
      the specificity and sensitivity of CD4+CD127low/- cells are comparable to those
      of CD4+FoxP3+, which is the gold standard, and can be used as an alternative.
      This novel flow cytometric antibody panel with fewer number of antibodies is cost
      effective and can be used to enumerate Tregs in resource-limited settings.

PMID- 22989356
TI  - A new procedure for race analysis in swimming based on individual distance
      measurements.
AB  - The aim of this study was to develop a new application based on the "individual
      distances" method to analyse swimming races, and to compare it with the
      traditional "fixed distances" method. One hundred and seventy-nine national level
      100 m (four strokes) performances obtained from the 2008 "Open Comunidad de
      Madrid" (Spain) were analysed using a two-dimensional Direct Linear
      Transformation (2D-DLT) video analysis system. Average velocities in all race
      segments (P < 0.001) were faster using the "individual distances" method than
      when employing the "fixed distances" method. Specifically, start and turn times
      were shorter (P < 0.001) while free swimming times were longer (P < 0.001) when
      using the "individual distances" method. Correlations between methods were
      moderate to high, but several gender and stroke groups showed poor to no
      correlation, especially during the start and turn segments. Differences between
      methods were higher in some groups (female swimmers and freestyle stroke) where
      the start and turn distances were shorter. Measurements with the 2D-DLT technique
      provide distances and times employed during the race segments, which do not
      completely agree with times at fixed distances. Therefore, when evaluating
      swimming races, a combination of the individual and fixed distances methods
      should be used.

PMID- 22989354
TI  - Deficiency of terminal complement pathway inhibitor promotes neuronal tau
      pathology and degeneration in mice.
AB  - BACKGROUND: The neuronal microtubule-associated protein tau becomes
      hyperphosphorylated and forms aggregates in tauopathies but the processes leading
      to this pathological hallmark are not understood. Because tauopathies are
      accompanied by neuroinflammation and the complement cascade forms a key innate
      immune pathway, we asked whether the complement system has a role in the
      development of tau pathology. FINDINGS: We tested this hypothesis in two mouse
      models, which expressed either a central inhibitor of complement or lacked an
      inhibitor of the terminal complement pathway. Complement receptor-related
      gene/protein y is the natural inhibitor of the central complement component C3 in
      rodents. Expressing a soluble variant (sCrry) reduced the number of phospho-tau
      (AT8 epitope) positive neurons in the brain stem, cerebellum, cortex, and
      hippocampus of aged P301L mutant tau/sCrry double-transgenic mice compared with
      tau single-transgenic littermates (JNPL3 line). CD59a is the major inhibitor of
      formation of the membrane attack complex in mice. Intrahippocampal injection of
      adeno-associated virus encoding mutant human P301L tau into Cd59a-/- mice
      resulted in increased numbers of AT8-positive cells compared with wild-type
      controls. This was accompanied by neuronal and synaptic loss and reduced
      dendritic integrity. CONCLUSIONS: Our data in two independent mouse models with
      genetic changes in key regulators of the complement system support the hypothesis
      that the terminal pathway has an active role in the development of tau pathology.
      We propose that inhibition of the terminal pathway may be beneficial in
      tauopathies.

PMID- 22989357
TI  - Reactions of the unsaturated hydroxo complex [W2Cp2(OH)(MU-PPh2)2(CO)]BF4 with
      mono- and bidentate ligands having E-H bonds (E = O, S, N).
AB  - The title compound reacted with CO at room temperature in the presence of excess
      HBF(4).OEt(2) to yield a mixture of the electron-precise complexes [W(2)Cp(2)(MU
      PPh(2))(2)(CO)(4)](BF(4))(2) and [W(2)Cp(2)(MU
      PPh(2))(2)(CO)(3)(OH(2))](BF(4))(2), with the aquo ligand in the latter complex
      being easily displaced by simple donors such as acetonitrile. Reaction of the
      title complex with simple acidic molecules such as HSPh or HBr took place rapidly
      with elimination of H(2)O to give the 32-electron cations [W(2)Cp(2)(Z)(MU
      PPh(2))(2)(CO)](+) [Z = Br, SPh (W-W = 2.8076(9) A)], which were reversibly
      carbonylated to give the electron-precise derivatives [W(2)Cp(2)(MU-Z)(MU
      PPh(2))(2)(CO)(2)](+). Reaction with hydrogen sulfide likely proceeded
      analogously, but also involved fast cleavage of the second S-H bond to give the
      sulfido hydride cation [W(2)Cp(2)(MU-H)(MU-PPh(2))(2)(S)(CO)](+). Deprotonation
      of the latter cation with 1,8-diazabicycloundec-7-ene (DBU) in the presence of
      excess H(2)S gave a mixture of the corresponding sulfido and disulfido complexes
      [W(2)Cp(2)(MU-PPh(2))(2)(S)(CO)] and [W(2)Cp(2)(kappa(2)-S(2))(MU
      PPh(2))(2)(CO)]. Reactions of [W(2)Cp(2)(OH)(MU-PPh(2))(2)(CO)]BF(4) with several
      bidentate ligands (L(2)H) having weakly acidic H atoms (L(2) = SC(5)H(4)N,
      SC(6)H(4)NH(2), NHC(S)Ph) gave the unsaturated chelate derivatives
      [W(2)Cp(2)(kappa(2)-L(2))(MU-PPh(2))(2)(CO)]BF(4). The N-H bonds in the latter
      cations could be further deprotonated with strong bases (DBU or NaOH) to give
      neutral derivatives displaying either chelate (N,S-SC(6)H(4)NH) or imido-like
      terminal ligands (N-NC(S)Ph), respectively. The related chelate complex
      [W(2)Cp(2)(O,O'-OC(6)H(4)O)(MU-PPh(2))(2)(CO)] (W-W = 2.836(1) A) was obtained in
      high yield from the reaction of the thiolato complex [W(2)Cp(2)(SPh)(MU
      PPh(2))(2)(CO)]BF(4) with catechol in the presence of DBU.

PMID- 22989360
TI  - Comparison of chemical composition and antibacterial activity of lavender
      varieties from Poland.
AB  - The aim of the study was comparing the chemical composition of the essential oils
      from five varieties of lavender (Lavandula angustifolia L.), and its biological
      activity against two pathogenic bacteria, Staphylococcus aureus and Pseudomonas
      aeruginosa. In the comparison we included the following varieties: 'Munstead',
      'Munstead Strain', 'Lavender Lady', 'Ellegance Purple' and 'Blue River'. Selected
      varieties of lavender (L. angustifolia) are characterised by exactly the same
      main compounds with only variations in the percentage of content. The primary
      components of the essential oils were: linalool (23.9-15.8%), linalyl
      anthranilate (12.3-1.6%), 1-terpinen-4-ol (9.7-5.5%), p-menth-1-en-8-ol (7.9
      4.0%) and linalool oxide (4.7-1.1%). From the essential oils that were tested,
      the 'Blue River' and 'Munstead' varieties have the greatest antibacterial
      activity against S. aureus and P. aeruginosa. 

PMID- 22989359
TI  - The OPTIMIST study: optimisation of cost effectiveness through individualised FSH
      stimulation dosages for IVF treatment. A randomised controlled trial.
AB  - BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due
      to the use of follicle stimulating hormone (FSH). FSH is usually administered in
      a standard dose. However, due to differences in ovarian reserve between women,
      ovarian response also differs with potential negative consequences on pregnancy
      rates. A Markov decision-analytic model showed that FSH dose individualisation
      according to ovarian reserve is likely to be cost-effective in women who are
      eligible for IVF. However, this has never been confirmed in a large randomised
      controlled trial (RCT). The aim of the present study is to assess whether an
      individualised FSH dose regime based on an ovarian reserve test (ORT) is more
      cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in
      subfertile women indicated for a first IVF or intracytoplasmic sperm injection
      cycle, who are aged < 44 years, have a regular menstrual cycle and no major
      abnormalities at transvaginal sonography. Women with polycystic ovary syndrome,
      endocrine or metabolic abnormalities and women undergoing IVF with oocyte
      donation, will not be included. Ovarian reserve will be assessed by measuring the
      antral follicle count. Women with a predicted poor response or hyperresponse will
      be randomised for a standard versus an individualised FSH regime (150 IU/day, 225
      450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of
      three stimulation cycles during maximally 18 months. The primary study outcome is
      the cumulative ongoing pregnancy rate resulting in live birth achieved within 18
      months after randomisation. Secondary outcomes are parameters for ovarian
      response, multiple pregnancies, number of cycles needed per live birth, total IU
      of FSH per stimulation cycle, and costs. All data will be analysed according to
      the intention-to-treat principle. Cost-effectiveness analysis will be performed
      to assess whether the health and associated economic benefits of individualised
      treatment of subfertile women outweigh the additional costs of an ORT.
      DISCUSSION: The results of this study will be integrated into a decision model
      that compares cost-effectiveness of the three dose-adjustment strategies to a
      standard dose strategy. The study outcomes will provide scientific foundation for
      national and international guidelines. TRIAL REGISTRATION: NTR2657.

PMID- 22989361
TI  - Uniformly cationized protein efficiently reaches the cytosol of mammalian cells.
AB  - Protein cationization techniques are powerful protein transduction methods for
      mammalian cells. As we demonstrated previously, cationized proteins with limited
      conjugation to polyethylenimine have excellent ability to enter into cells by
      adsorption-mediated endocytosis [Futami, J., et al. (2005) J. Biosci. Bioeng. 99,
      95-103]. In this study, we show that proteins with extensive and uniform
      cationization covering the protein surface reach the cytoplasm and nucleus more
      effectively than proteins with limited cationic polymers or proteins that are
      fused to cationic peptides. Although extensive modification of carboxylates
      results in loss of protein function, chicken avidin retains biotin-binding
      ability even after extensive amidation of carboxylates. Using this cationized
      avidin carrier system, the protein transduction ability of variously cationized
      avidins was investigated using biotinylated protein as a probe. The results
      revealed that cationized avidins bind rapidly to the cell surface followed by
      endocytotic uptake. Small amounts of uniformly cationized avidin showed direct
      penetration into the cytoplasm within a 15 min incubation. This penetration route
      seemed to be energy dependent and functioned under cellular physiological
      conditions. A biotinylated exogenous transcription factor protein that penetrated
      cells was demonstrated to induce target gene expression in living cells.

PMID- 22989362
TI  - History of lower limb reconstruction after trauma.
AB  - BACKGROUND: The principles guiding reconstruction of the lower limb after trauma
      have become established over 300 years through advances in technology and studies
      of epidemiology. This paper reviews how these principles came about and why they
      are important. METHODS: This is a structured review of historical and recent
      literature pertinent to lower limb reconstruction. The outcomes assessed in the
      pre-modern era were wound mortality, amputation mortality and amputation rate. In
      the modern era, infection and non-union emerged as measures of outcome, which are
      morbidity- rather than mortality-based. Indications for amputation published
      during the eras are taken to reflect the reconstructive practices of the time.
      RESULTS: Amputation and wound mortality fell throughout the pre-modern era, from
      70% and 20% to 1.8% and 1.8%, respectively. Amputation rates peaked in the
      American Civil War (53%) but have remained less than 20% since then. Infection
      and non-union rates in the modern era have fluctuated between 5% and 45%.
      CONCLUSIONS: Priority areas for research include refinement of soft tissue
      reconstruction, injury classification, standardization of outcome measures and
      primary prevention. The impact of debridement and antisepsis on outcomes should
      not be forgotten as progress is made.

PMID- 22989363
TI  - Flavonoid dimers as novel, potent antileishmanial agents.
AB  - The present study found that synthetic flavonoid dimers with either polyethylene
      glycol linker or amino ethyleneglycol linker have marked leishmanicidal activity.
      Compound 39 showed very consistent and promising leishmanicidal activity for both
      extracellular promastigotes (IC50 ranging from 0.13 to 0.21 MUM) and
      intracellular amastigotes (IC50 = 0.63 MUM) irrespective of the drug-sensitivity
      of parasites. Moreover, compound 39 displayed no toxicity toward macrophage RAW
      264.7 cells (IC50 > 100 MUM) and primary mouse peritoneal elicited macrophages
      (IC50 > 88 MUM). Its high value of therapeutic index (>140) was better than other
      highly potent antileishmanials such as amphotericin B (therapeutic index = 119).
      Compound 39 is therefore a new, safe, and effective antileishmanial candidate
      compound which is even effective against drug-refractory parasites.

PMID- 22989364
TI  - Is chemotherapy dose intensity adequate in breast cancer management in the
      Australian healthcare setting: a retrospective analysis.
AB  - AIM: To determine the adequacy of chemotherapy received dose intensity (RDI) in
      breast cancer treatment in a general population and to identify factors that
      influence RDI. METHODS: A retrospective analysis of breast cancer patients who
      commenced a course of i.v. chemotherapy in 2008 was undertaken. Data were
      collected on patient and tumor characteristics, chemotherapy regimen, dose
      (including delays, reductions and the reasons for these), granulocyte colony
      stimulating factor (G-CSF) use and febrile neutropenia incidence. RDI was
      calculated using the planned and actual dose received and time taken. A level of
      >=85% RDI was considered acceptable for treatment given with curative intent.
      RESULTS: In all, 131 patients (aged 28 to 77 years) received chemotherapy in
      adjuvant (n = 76, 58%), neoadjuvant (n = 11, 8%) and metastatic settings (n = 44,
      34%). RDI did not reach 85% for 12% adjuvant, 36% neoadjuvant and 34% metastatic
      cases (chi(2) = 10.55, P = 0.005). Overall, 43% of patients received G-CSF.
      CONCLUSION: Acceptable chemotherapy RDI was delivered for most patients in the
      adjuvant setting but not in the neoadjuvant setting. G-CSF treatment contributed
      to the optimization of dose intensity in the adjuvant setting only. Dose
      intensity in the metastatic setting was considered satisfactory where quality of
      life is the primary focus. Other factors can be modified to improve RDI.

PMID- 22989365
TI  - Social and economic burden of walking and mobility problems in multiple
      sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic progressive neurological disease
      and the majority of patients will experience some degree of impaired mobility. We
      evaluated the prevalence, severity and burden of walking and mobility problems
      (WMPs) in 5 European countries. METHODS: This was a cross-sectional, patient
      record-based study involving 340 neurologists who completed detailed patient
      record forms (PRF) for patients (>18 years) attending their clinic with MS.
      Patients were also invited to complete a questionnaire (PSC). Information
      collected included demographics, disease characteristics, work productivity,
      quality of life (QoL; EuroQol-5D and Hamburg Quality of Life Questionnaire
      Multiple Sclerosis [HAQUAMS]) and mobility (subjective patient-reported and
      objectively measured using the timed 25 foot walk test [T25FW]). Relationships
      between WMPs and disease and other characteristics were examined using Chi square
      tests. Analysis of variance was used to examine relationships between mobility
      measures and work productivity. RESULTS: Records were available for 3572 patients
      of whom 2171 also completed a PSC. WMPs were regarded as the most bothersome
      symptom by almost half of patients who responded (43%; 291/683). There was a
      clear, independent and strong directional relationship between severity of WMPs
      (subjective and objective) and healthcare resource utilisation. Patients with
      longer T25FW times (indicating greater walking impairment) were significantly
      more likely to require additional caregiver support (p < 0.0001), visit a variety
      of healthcare professionals including their primary care physicians (p = 0.0044)
      and require more long-term non-disease modifying drugs (p = 0.0001). A similar
      pattern was observed when subjective reporting of the severity of WMPs was
      considered. Work productivity was also markedly impacted by the presence of WMPs
      with fewer patients working full time and a reduction in weekly working hours as
      T25FW times and the subjective severity of WMPs increased. CONCLUSIONS: In
      Europe, WMPs in MS represent a considerable personal and social burden both
      financially and in terms of quality of life. Interventions to improve mobility
      could have significant benefits for patients and society as a whole.

PMID- 22989358
TI  - Testing hypotheses for genealogical discordance in a rainforest lizard.
AB  - Genealogical discordance, or when different genes tell distinct stories although
      they evolved under a shared history, often emerges from either coalescent
      stochasticity or introgression. In this study, we present a strong case of mito
      nuclear genealogical discordance in the Australian rainforest lizard species
      complex of Saproscincus basiliscus and S. lewisi. One of the lineages that
      comprises this complex, the Southern S. basiliscus lineage, is deeply divergent
      at the mitochondrial genome but shows markedly less divergence at the nuclear
      genome. By placing our results in a comparative context and reconstructing the
      lineages' demography via multilocus and coalescent-based approximate Bayesian
      computation methods, we test hypotheses for how coalescent variance and
      introgression contribute to this pattern. These analyses suggest that the
      observed genealogical discordance likely results from introgression. Further, to
      generate such strong discordance, introgression probably acted in concert with
      other factors promoting asymmetric gene flow between the mitochondrial and
      nuclear genomes, such as selection or sex-biased dispersal. This study offers a
      framework for testing sources of genealogical discordance and suggests that
      historical introgression can be an important force shaping the genetic diversity
      of species and their populations.

PMID- 22989366
TI  - Analysis of scalp EEG and quantitative MRI in cases of temporal lobe epilepsy
      requiring intracranial electrographic monitoring.
AB  - Abstract Purpose. Contradictory scalp electroencephalographic (sEEG) and
      discordant imaging features are common in temporal lobe epilepsy (TLE). We
      assessed the relative importance of sEEG features and their relation to
      quantitative magnetic resonance (MR) imaging measures in regard to surgical
      outcome. Methods and materials. Patients with a putative TLE underwent
      extraoperative electrocorticography (eECoG) with bitemporal subdural electrodes
      for clarification of the ictogenic source. Patients were categorized by sEEG
      ictal patterns (IPs) as showing unilateral or bilateral onset. Concordance with
      the side of resection, as determined by eECoG, to that suggested by the
      predominant sEEG IP was further analysed as: (a) entirely ipsilateral eECoG IPs
      with discordant nonelectrographic data; (b) ipsilateral preponderant (> 80%)
      eECoG IPs; and c) contralateral preponderant (> 80%) eECoG IPs. Quantitative
      hippocampal volumes and signal characteristics were applied for comparison.
      Results. Of 26 patients, eECoG confirmed a unilateral IP on sEEG in 19 (73%). Of
      these 19, exclusively ipsilateral sEEG interical epileptiform discharges (IEDs)
      were identified in 9 (47%). When bilateral, generalized, absent or contralateral
      IEDs were found, 6 cases (60%) still showed a preponderantly ipsilateral IP
      identifying the epileptogenic side. In patients with sEEG bilateral IPs, 5 (71%)
      also had bilateral IEDs. Of the 16 patients who underwent resection, 14 (87.5%)
      achieved favourable outcomes and 9 (56%), seizure cessation. Hippocampal
      volumetry in 23 patients correctly lateralized 7 (30%) whereas fluid-attenuated
      inversion recovery (FLAIR) signal measures applied in 23 patients lateralized 9
      (39%). Conclusions. Favourable surgical outcomes are attainable following eECoG
      in cases where ambiguity exists regarding the laterality of TLE on sEEG, even for
      those in whom bilateral IPs and either bilateral or no IEDs are demonstrated on
      sEEG. Neither volumetric nor FLAIR signal ratios were sufficiently reliable for
      lateralizing TLE in the majority of cases.

PMID- 22989367
TI  - Effect of a GaAsP shell on the optical properties of self-catalyzed GaAs
      nanowires grown on silicon.
AB  - We realize the growth of self-catalyzed core-shell GaAs/GaAsP nanowires (NWs) on
      Si substrates using molecular-beam epitaxy. Transmission electron microscopy of
      single GaAs/GaAsP NWs demonstrates their high crystal quality and shows
      domination of the GaAs zinc-blende phase. Using continuous-wave and time-resolved
      photoluminescence (PL), we make a detailed comparison with uncapped GaAs NWs to
      emphasize the effect of the GaAsP capping in suppressing the nonradiative surface
      states. Significant PL enhancement in the core-shell structures exceeding 3
      orders of magnitude at 10 K is observed; in uncapped NWs PL is quenched at 60 K,
      whereas single core-shell GaAs/GaAsP structures exhibit bright emission even at
      room temperature. From analysis of the PL temperature dependence in both types of
      NW we are able to determine the main carrier escape mechanisms leading to the PL
      quench.

PMID- 22989368
TI  - Diagnostic accuracy of punch biopsy in subtyping basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in humans.
      The histological subtype reported by punch biopsy may influence the type of
      treatment. Few studies have investigated the accuracy of punch biopsy in
      diagnosing the true BCC subtype. OBJECTIVE: To determine the accuracy,
      sensitivity and specificity of punch biopsy in BCC subtype diagnosis. METHODS: In
      this retrospective study, 333 biopsy specimens and excisions were reviewed.
      Histological subtypes present in the initial biopsy were compared with tumour
      subtypes of the total excision. RESULTS: The concordance between the BCC subtype
      present in the biopsy specimen and in the subsequent excision specimen was 72.3%.
      The most common BCC patterns were nodular (158, 47.5%) and mixed subtype (90,
      27%). Most mixed tumours contained one or more aggressive subtype (63/90, 70%).
      In 47/120 (39.1%) aggressive tumours (14.1% of the total), punch biopsy failed to
      correctly identify the aggressive component. The most commonly missed aggressive
      subtype was mixed aggressive including nodular/micronodular and
      nodular/infiltrative (30/47, 63.8%). In 45/213 (21.1%) non-aggressive BCCs (13.5%
      of total cases), punch biopsy incorrectly reported an aggressive subtype. The
      most commonly misidentified non-aggressive subtype was nodular (39/45, 86.6). The
      sensitivity and specificity of punch biopsy in diagnosing aggressive vs. non
      aggressive BCC subtypes 60.8% (95% CI, 51.9-69.1) and 78.9% (95% CI, 72.8-83.8),
      respectively. The positive and negative predictive values were 61.9% and 78.1%,
      respectively. CONCLUSION: Punch biopsy has serious pitfalls in differentiating
      aggressive and non-aggressive BCC subtypes. Dermatologists should consider the
      possibility of aggressive components within non-aggressive BCCs reported using
      punch biopsy.

PMID- 22989369
TI  - Experiences of young people who have undergone the Lightning Process to treat
      chronic fatigue syndrome/myalgic encephalomyelitis--a qualitative study.
AB  - OBJECTIVES: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a
      serious condition characterized by debilitating but unexplained fatigue.
      Treatment alternatives are few, and especially so for young people. The aetiology
      of CFS/ME is still unclear and controversial, but rehabilitative interventions
      seem so far most promising. The Lightning Process is a 3-day training programme
      that has recently become available, but no outcome studies have yet been
      published. It is a non-medical training programme that combines concepts from
      Neuro-Linguistic Programming, Life Coaching and Osteopathy. The aim of this study
      was to explore the experiences of young people with CFS/ME after they had
      undergone the Lightning Process. DESIGN: Qualitative research study. METHODS:
      Semi-structured interviews were conducted with an opportunistic sample recruited
      through open advertisements of nine young people, aged 14-26, who had undergone
      the treatment, and three of their parents. Inductive thematic analysis was used
      to evaluate the content of the interviews. RESULTS: Mostly positive experiences
      were reported of the Lightning Process. Two reported dissatisfaction and no
      improvement, while seven were satisfied and were much improved. Particular
      helpful aspects were the theoretical rationale, practical exercises, and the
      technique they learned. Less helpful aspects were the intensity and short
      duration of the treatment with little follow-up, the secrecy surrounding it, and
      feelings of being blamed if the treatment did not work. CONCLUSIONS: As this is
      the first report of young people's experiences with the Lightning Process, it
      will be important to consider the helpful and unhelpful treatment components for
      future refinement of interventions for CFS/ME.

PMID- 22989370
TI  - Co-grafting of amino-poly(ethylene glycol) and Magainin I on a TiO2 surface:
      tests of antifouling and antibacterial activities.
AB  - An antimicrobial peptide, Magainin I (Mag), was grafted to a titanium oxide
      surface, via an antiadhesive poly(ethylene glycol) (PEG) cross-linker. The latter
      plays a 2-fold part, being antiadhesive, and enabling the covalent immobilization
      of the peptide. The functionalization was characterized at each step by
      reflection absorption infrared spectroscopy (RAIRS) and X-ray photoelectron
      spectroscopy (XPS). The antiadhesive properties of PEG, and antibacterial
      activity of the anchored Magainin I, were individually tested toward adsorption
      of bovin serum albumin (BSA) proteins, and against Gram positive bacteria,
      Listeria ivanovii , respectively. The results reveal that adhesion of both
      proteins and bacteria have been considerably reduced, accompanied by an
      inhibition of the growth of remaining adhered bacteria. This work thus offers a
      novel approach to functionalize oxide surfaces against biofilms and to measure
      the so-obtained properties in each of the successive steps of a biofilm
      formation.

PMID- 22989371
TI  - Successful treatment for adrenocorticotropic hormone-independent macronodular
      adrenal hyperplasia with laparoscopic adrenalectomy: a case series.
AB  - INTRODUCTION: Adrenocorticotropic hormone-independent macronodular adrenal
      hyperplasia, characterized by bilateral macronodular adrenal hypertrophy and
      autonomous cortisol production, is a rare cause of Cushing's syndrome. Bilateral
      adrenalectomy is considered the standard treatment for adrenocorticotropic
      hormone-independent macronodular adrenal hyperplasia but obliges the patient to
      receive lifetime steroid replacement therapy subsequently, and may increase the
      patient's risk of adrenal insufficiency. These circumstances require surgeons to
      carefully consider operative strategies on an individual basis. CASE
      PRESENTATION: We performed successful laparoscopic adrenalectomy on four patients
      with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia.
      Computed tomography scans showed bilateral adrenal enlargement in all patients.
      Case 1: a 56-year-old Japanese woman presented with obvious Cushing's symptoms
      during treatment for diabetes mellitus and hypertension. Case 2: a 37-year-old
      Japanese man also presented with Cushing's symptoms during treatment for diabetes
      mellitus and hypertension. These patients were diagnosed as Cushing's syndrome
      caused by adrenocorticotropic hormone-independent macronodular adrenal
      hyperplasia based on endocrinologic testing, and underwent bilateral laparoscopic
      adrenalectomy. Case 3: an 80-year-old Japanese woman was hospitalized due to
      unusual weight gain and heightened general fatigue, and was diagnosed as
      Cushing's syndrome caused by adrenocorticotropic hormone-independent macronodular
      adrenal hyperplasia. She underwent unilateral laparoscopic adrenalectomy due to
      high operative risk. Case 4: a 66-year-old Japanese man was discovered to have
      bilateral adrenal tumors on medical examination. He did not have Cushing's
      symptoms and was diagnosed as subclinical Cushing's syndrome due to suppressed
      adrenocorticotropic hormone serum levels and loss of cortisol circadian rhythm
      without abnormal levels of serum cortisol. He underwent unilateral laparoscopic
      adrenalectomy. During follow-up, serum cortisol levels were within the normal
      range in all cases, and serum adrenocorticotropic hormone levels were not
      suppressed. Further, cases with Cushing's syndrome experienced clinical
      improvement. CONCLUSIONS: We were able to effectively treat adrenocorticotropic
      hormone-independent macronodular adrenal hyperplasia in patients with obvious
      Cushing's symptoms by laparoscopic bilateral adrenalectomy, which promptly
      improved symptoms. Further, unilateral adrenalectomy was effective for treating
      an older patient at high operative risk and a patient with subclinical Cushing's
      syndrome.

PMID- 22989372
TI  - Airway responses and inflammation in subjects with asthma after four days of
      repeated high-single-dose allergen challenge.
AB  - BACKGROUND: Both standard and low-dose allergen provocations are an established
      tool in asthma research to improve our understanding of the pathophysiological
      mechanism of allergic asthma. However, clinical symptoms are less likely to be
      induced. Therefore, we designed a protocol for repetitive high-dose bronchial
      allergen challenges to generate clinical symptoms and airway inflammation.
      METHODS: A total of 27 patients aged 18 to 40 years with positive skin-prick
      tests and mild asthma underwent repetitive high-dose allergen challenges with
      household dust mites for four consecutive days. Pulmonary function and exhaled NO
      were measured at every visit. Induced sputum was analysed before and after the
      allergen challenges for cell counts, ECP, IL-5, INF-gamma, IL-8, and the
      transcription factor Foxp3. RESULTS: We found a significant decrease in pulmonary
      function, an increased use of salbutamol and the development of a late asthmatic
      response and bronchial hyperresponsiveness, as well as a significant induction of
      eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the
      majority of patients. Two subjects had severe adverse events requiring
      prednisolone to cope with nocturnal asthma symptoms. CONCLUSIONS: Repeated high
      dose bronchial allergen challenges resulted in severe asthma symptoms and marked
      Th-2-mediated allergic airway inflammation. The high-dose challenge model is
      suitable only in an attenuated form in diseased volunteers for proof-of-concept
      studies and in clinical settings to reduce the risk of severe asthma
      exacerbations. TRIAL REGISTRATION: ClinicalTrials.govNCT00677209.

PMID- 22989373
TI  - Benefits of pharmaceutical innovation: the case of simvastatin in Canada.
AB  - BACKGROUND: The benefits of pharmaceutical innovations are widely diffused; they
      accrue to the healthcare providers, patients, employers, and manufacturers. We
      estimate the societal monetary benefits of simvastatin in Canada and its
      distribution among different beneficiaries overtime. METHODS: Monetary benefits
      to developing and generic manufacturers were estimated by calculating public and
      private revenues minus the development costs of simvastatin and the contribution
      toward further research and development. We used a dynamic Markov model to
      estimate monetary benefits to healthcare and employment sectors in terms of cost
      avoidance associated with prevented cardiovascular events, including stroke and
      myocardial infarction, and lost productivity due to disability and premature
      death in working population. RESULTS: Cumulative monetary benefits of simvastatin
      from 1990 to 2009 were $4.8 billion (2010 CA$), of which developing and generic
      manufacturers, and healthcare and employment sectors accounted for 32 percent, 27
      percent, 32 percent, and 9 percent, respectively. The yearly trend showed that
      after the patent expired in 2002 the generic manufacturers became dominant in the
      market. Benefits for the healthcare sector started to decrease from 2003
      corresponding to the decreasing population taking simvastatin during the same
      time period. Sensitivity analysis showed the higher the compliance or the
      efficacy, the larger the benefits to healthcare and employment sectors, while
      monetary benefits for manufacturers were unchanged. CONCLUSIONS: Societal
      monetary benefits of simvastatin are significant and the distributions of the
      benefits have changed overtime. Patent, compliance, and efficacy play a vital
      role in the estimation of the benefits. Analysis of all beneficiaries separately
      overtime is important when assessing the value of pharmaceutical innovation.

PMID- 22989374
TI  - Involvement of microRNA-224 in cell proliferation, migration, invasion, and anti
      apoptosis in hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Changes in microRNA (miRNA) expression have been detected in
      a broad range of biological processes including cancer. Here we determined the
      role of miRNA dysregulation in hepatocellular carcinoma (HCC). METHODS: We
      investigated the expression of nine cancer-related miRNAs in HCC. Among these,
      miR-224 was the most significantly uprgulated in HCC tissues (n = 18), compared
      with normal (n = 9) and HCC adjacent non-tumorous liver tissues (n = 18). After
      leading-in currently reported gene targets from Sanger miRBase, we characterized
      the expression profiles of target genes of miR-224 using cDNA microarray. The
      altered expression was subsequently validated by real-time polymerase chain
      reaction and Western blot. The phenotypic changes by miR-224 expression were
      identified by cell viability, apoptosis, and in vitro scratch assays. RESULTS:
      The microarray analysis and miRNA target prediction analysis allowed the
      identification of significant changes in 68 putative gene targets after
      overexpression of miR-224. The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and
      MAPK1 were confirmed as important targets of miR-224 and involvement in
      hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7
      cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA
      and protein levels. Similar changes in the expression of the same genes were also
      observed in HCC tissues. Via functional analyses, cell proliferation, migration
      and anti-apoptosis were proved to be affected by miR-224 expression. CONCLUSION:
      The results suggest that miR-224 plays a role in cell proliferation, migration,
      invasion, and anti-apoptosis in HCC by directly binding to its gene targets,
      implicating this RNA in HCC development and progression.

PMID- 22989376
TI  - Study on the volatile oil contents of Annona glabra L., Annona squamosa L.,
      Annona muricata L. and Annona reticulata L., from Vietnam.
AB  - The volatile compounds identified from four species of Annona from Vietnam are
      being reported. The oils were obtained from aliquots of plant samples by steam
      distillation and subjected to GC and GC-MS analysis. The main compounds of Annona
      glabra L., were beta-caryophyllene (21.5%) germacrene D (17.7%), alpha-cadinol
      (5.4%) and beta-elemene (5.2%). Annona squamosa L., comprised mainly of alpha
      pinene (1.0-11.9%), limonene (0.8-11.7%), beta-cubebene (0.5-13.0%), beta
      caryophyllene (11.6-24.5%), spathulenol (0.8-9.0%), caryophyllene oxide (1.0
      10.6%) and alpha-cadinol (3.3-7.8%). The significant constituents of Annona
      muricata L., were alpha-pinene (9.4%), beta-pinene (20.6%), rho-mentha-2,4(8)
      diene (9.8%), beta-elemene (9.1%) and germacrene D (18.1%). However, camphene
      (0.2-6.6%), alpha-copaene (2.0-7.3%), beta-elemene (5.9-16.6%), beta
      caryophyllene (8.3-14.9%), beta-bisabolene (0.4-10.2%), delta-cadinene (1.7-4.8%)
      and germacrene D (9.3-22.8%) were the main compounds common to samples of Annona
      reticulata L. There were significant amounts of sabinene (11.2% and 2.7%; leaf
      and stem bark) and bicycloelemene (9.6% and 6.1%; stem and bark). 

PMID- 22989375
TI  - Domestication and geographic origin of Oryza sativa in China: insights from
      multilocus analysis of nucleotide variation of O. sativa and O. rufipogon.
AB  - Previous studies have indicated that China is one of the domestication centres of
      Asian cultivated rice (Oryza sativa), and common wild rice (O. rufipogon) is the
      progenitor of O. sativa. However, the number of domestication times and the
      geographic origin of Asian cultivated rice in China are still under debate. In
      this study, 100 accessions of Asian cultivated rice and 111 accessions of common
      wild rice in China were selected to examine the relationship between O. sativa
      and O. rufipogon and thereby infer the domestication and evolution of O. sativa
      in China through sequence analyses of six gene regions, trnC-ycf6 in chloroplast
      genomes, cox3 in mitochondrial genomes and ITS, Ehd1, Waxy, Hd1 in nuclear
      genomes. The results indicated that the two subspecies of O. sativa (indica and
      japonica) were domesticated independently from different populations of O.
      rufipogon with gene flow occurring later from japonica to indica; Southern China
      was the genetic diversity centre of O. rufipogon, and the Pearl River basin near
      the Tropic of Cancer was the domestication centre of O. sativa in China.

PMID- 22989377
TI  - Haem oxygenase-1 overexpression alters intracellular iron distribution.
AB  - Induction or ectopic overexpression of HO-1 (haem oxygenase 1) protects against a
      wide variety of disorders. These protective effects have been variably ascribed
      to generation of carbon monoxide (released during cleavage of the alpha-methene
      bridge of haem) and/or to production of the antioxidant bilirubin. We
      investigated HO-1-overexpressing A549 cells and find that, as expected, HO-1
      overexpressing cells are resistant to killing by hydrogen peroxide. Surprisingly,
      these cells have approximately twice the normal amount of intracellular iron
      which usually tends to amplify oxidant killing. However, HO-1-overexpressing
      cells contain only ~25% as much 'loose' (probably redox active) iron. Indeed,
      inhibition of ferritin synthesis [via siRNA (small interfering RNA) directed at
      the ferritin heavy chain] sensitizes the HO-1-overexpressing cells to peroxide
      killing. It appears that HO-1 overexpression leads to enhanced destruction of
      haem, consequent 2-3-fold induction of ferritin, and compensatory increases in
      transferrin receptor expression and haem synthesis. However, there is no
      functional haem deficiency because cellular oxygen consumption and catalase
      activity are similar in both cell types. We conclude that, at least in many
      cases, the cytoprotective effects of HO-1 induction or forced overexpression may
      derive from elevated expression of ferritin and consequent reduction of redox
      active 'loose' iron.

PMID- 22989378
TI  - TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients
      treated with Glatiramer acetate or Natalizumab.
AB  - BACKGROUND: The balance between T helper cells Th2- and Th1-related cytokines
      plays a key role in multiple sclerosis (MS). A shift from a Th1 towards a Th2
      cytokine profile could have a beneficial effect on the clinical course of the
      disease. The objective of this study was to assess Th2/Th1 cytokine profile in
      relapsing-remitting MS (RRMS) patients receiving an immunosuppressive treatment
      with natalizumab (NAT), or an immunomodulatory treatment with glatiramer acetate
      (GA) after one year of treatment. METHODS: This was an observational cross
      sectional study. All consecutive patients diagnosed with RRMS who had received GA
      or NAT for 12 months were included in the study. We determined serum levels of
      Th1 and Th2 cytokines (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8,
      IL-10, IL-12p70, IL-13, monocyte chemotactic protein [MCP]-1, tumor-necrosis
      factor [TNF]-alpha, interferon [IFN]-gamma and granulocyte macrophage colony
      stimulating factor [GM-CSF]) by flow cytometry. Th2/Th1 bias was defined based on
      the ratio of IL-4, IL-5, IL-6 or IL-10 Th2 cytokines and proinflammatory INF
      gamma or TNF-alpha Th1 cytokines. RESULTS: Eleven patients under treatment with
      NAT and 12 patients treated with GA were evaluated. RRMS patients treated with
      NAT showed significantly higher levels of IL-6 (p < 0.05), MCP-1 (p < 0.01), and
      GM-CSF (p < 0.05) compared to GA patients after one year of treatment. A trend
      for increasing of IL-12p70, IL-1b, TNF- alpha and IFN- gamma levels was also
      found in patients receiving NAT compared to GA patients. IL-4/IFN-gamma, IFN
      gamma/TNF-alpha and IL-10/IFN-gamma ratios as markers of Th2/Th1 ratio were
      significantly elevated in GA patients compared to those receiving NAT (p < 0.05).
      CONCLUSION: In conclusion, our findings suggest that GA promotes a superior Th2
      biased anti-inflammatory response as compared with NAT in the systemic
      circulation of RRMS patients. Future studies with larger cohorts will determine
      whether this immune Th2 shift in GA patients is associated with a beneficial
      effect on disease outcome.

PMID- 22989379
TI  - Synthesis and biological evaluation of 1alpha,25-dihydroxyvitamin D3 analogues
      with a long side chain at C12 and short C17 side chains.
AB  - Structure-guided optimization was used to design new analogues of 1alpha,25
      dihydroxyvitamin D3 bearing the main side chain at C12 and a shorter second
      hydroxylated chain at C17. The new compounds 5a-c were efficiently synthesized
      from ketone 9 (which is readily accessible from the Inhoffen-Lythgoe diol) with
      overall yields of 15%, 6%, and 3% for 5a, 5b, and 5c, respectively. The triene
      system was introduced by the Pd-catalyzed tandem cyclization-Suzuki coupling
      method. The new analogues were assayed against human colon and breast cancer cell
      lines and in mice. All new vitamin D3 analogues bound less strongly to the VDR
      than 1alpha,25-dihydroxyvitamin D3 but had similar antiproliferative, pro
      differentiating, and transcriptional activity as the native hormone. In vivo, the
      three analogues had markedly low calcemic effects.

PMID- 22989380
TI  - [European Association of Urology guidelines on laser technologies].
AB  - CONTEXT: The European Association of Urology (EAU) Guidelines Office has set up a
      guideline working panel to analyse the scientific evidence published in the world
      literature on lasers in urologic practice. OBJECTIVE: Review the physical
      background and physiologic and technical aspects of the use of lasers in urology,
      as well as current clinical results from these new and evolving technologies,
      together with recommendations for the application of lasers in urology. The
      primary objective of this structured presentation of the current evidence base in
      this area is to assist clinicians in making informed choices regarding the use of
      lasers in their practice. EVIDENCE ACQUISITION: Structured literature searches
      using an expert consultant were designed for each section of this document.
      Searches were carried out in the Cochrane Database of Systematic Reviews, the
      Cochrane Central Register of Controlled Trials, and Medline and Embase on the
      Dialog/DataStar platform. The controlled terminology of the respective databases
      was used, and both Medical Subject Headings and EMTREE were analysed for relevant
      entry terms. One Cochrane review was identified. EVIDENCE SYNTHESIS: Depending on
      the date of publication, the evidence for different laser treatments is
      heterogeneous. The available evidence allows treatments to be classified as safe
      alternatives for the treatment of bladder outlet obstruction in different
      clinical scenarios, such as refractory urinary retention, anticoagulation, and
      antiplatelet medication. Laser treatment for bladder cancer should only be used
      in a clinical trial setting or for patients who are not suitable for conventional
      treatment due to comorbidities or other complications. For the treatment of
      urinary stones and retrograde endoureterotomy, lasers provide a standard tool to
      augment the endourologic procedure. CONCLUSIONS: In benign prostatic obstruction
      (BPO), laser vaporisation, resection, or enucleation are alternative treatment
      options. The standard treatment for BPO remains transurethral resection of the
      prostate for small to moderate size prostates and open prostatectomy for large
      prostates. Laser energy is an optimal treatment method for disintegrating urinary
      stones. The use of lasers to treat bladder tumours and in laparoscopy remains
      investigational.

PMID- 22989381
TI  - Derivation and characterization of sleeping beauty transposon-mediated porcine
      induced pluripotent stem cells.
AB  - The domestic pig is an important large animal model for preclinical testing of
      novel cell therapies. Recently, we produced pluripotency reporter pigs in which
      the Oct4 promoter drives expression of the enhanced green fluorescent protein
      (EGFP). Here, we reprogrammed Oct4-EGFP fibroblasts employing the nonviral
      Sleeping Beauty transposon system to deliver the reprogramming factors Oct4,
      Sox2, Klf4, and cMyc. Successful reprogramming to a pluripotent state was
      indicated by changes in cell morphology and reactivation of the Oct4-EGFP
      reporter. The transposon-reprogrammed induced pluripotent stem (iPS) cells showed
      long-term proliferation in vitro over >40 passages, expressed transcription
      factors typical of embryonic stem cells, including OCT4, NANOG, SOX2, REX1,
      ESRRB, DPPA5, and UTF1 and surface markers of pluripotency, including SSEA-1 and
      TRA-1-60. In vitro differentiation resulted in derivatives of the 3 germ layers.
      Upon injection of putative iPS cells under the skin of immunodeficient mice, we
      observed teratomas in 3 of 6 cases. These results form the basis for in-depth
      studies toward the derivation of porcine iPS cells, which hold great promise for
      preclinical testing of novel cell therapies in the pig model.

PMID- 22989382
TI  - Biotite dissolution in brine at varied temperatures and CO2 pressures: its
      activation energy and potential CO2 intercalation.
AB  - For sustainable geologic CO(2) sequestration (GCS), it is important to understand
      the effects of temperature and CO(2) pressure on mica's dissolution and surface
      morphological changes under saline hydrothermal conditions. Batch experiments
      were conducted with biotite (Fe-end member mica) under conditions relevant to GCS
      sites (35-95  degrees C and 75-120 atm CO(2)), and 1 M NaCl solution was used to
      mimic the brine. With increasing temperature, a transition from incongruent to
      congruent dissolution of biotite was observed. The dissolution activation energy
      based on Si release was calculated to be 52 +/- 5 kJ mol(-1). By comparison with
      N(2) experiments, we showed that CO(2) injection greatly enhanced biotite's
      dissolution and its surface morphology evolutions, such as crack formation and
      detachment of newly formed fibrous illite. For biotite's dissolution and
      morphological evolutions, the pH effects of CO(2) were differentiated from the
      effects of bicarbonate complexation and CO(2) intercalation. Bicarbonate
      complexation effects on ion release from biotite were found to be minor under our
      experimental conditions. On the other hand, the CO(2) molecules in brine could
      get into the biotite interlayer and cause enhanced swelling of the biotite
      interlayer and hence the observed promotion of biotite surface cracking. The
      cracking created more reactive surface area in contact with brine and thus
      enhanced the later ion release from biotite. These results provide new
      information for understanding CO(2)-brine-mica interactions in saline aquifers
      with varied temperatures and CO(2) pressures, which can be useful for GCS site
      selection and operations.

PMID- 22989384
TI  - Surgical location and anatomical variations of pudendal nerve.
AB  - BACKGROUND: An objective of our work was to clarify variations in pudendal nerve
      formation, as well as their possible impact on the clinical picture. METHOD:
      Bilateral pudendal nerve course and formation was studied on 20 adult cadavers.
      An anterior approach was used in 15 subjects, and both posterior and anterior
      approaches were used in five subjects. RESULTS: The prefixed type plexus
      formation was observed in eight cases (40%). In these cases, S(1)  and S(2) 
      roots contributed to the formation of the pudendal nerve. In the postfixed type,
      the S(3)  root was dominant in two cases (66.7%), and less the S(4)  root in one
      case (23.3%), albeit to a lesser degree. Most commonly, the S(2)  root
      participated in its formation in 17 cases (85%). The inferior rectal nerve
      penetrating the sacrospinous ligament was seen in one case, arising from the
      pudendal nerve before entering the pudendal canal in four cases. The dorsal nerve
      of the penis arose from the S(1)  root in two cases (10%). We observed it
      branching before entering the pudendal canal in 15 cases (75%), and it had
      divided in the pudendal canal in the other cases. For the posterior access, the
      pudendal nerve was localized 13.1 +/- 0.72 cm medial to the greater trochanter,
      8.1 +/- 0.72 cm above the ischial tuberosity, at a depth of 6.4 +/- 0.32 cm.
      CONCLUSIONS: This description may be useful when carrying out a pudendal nerve
      block and during surgical procedures carried out in this anatomical region.

PMID- 22989383
TI  - Differential responses of osteoblast lineage cells to nanotopographically
      modified, microroughened titanium-aluminum-vanadium alloy surfaces.
AB  - Surface structural modifications at the micrometer and nanometer scales have
      driven improved success rates of dental and orthopaedic implants by mimicking the
      hierarchical structure of bone. However, how initial osteoblast-lineage cells
      populating an implant surface respond to different hierarchical surface
      topographical cues remains to be elucidated, with bone marrow mesenchymal stem
      cells (MSCs) or immature osteoblasts as possible initial colonizers. Here we show
      that in the absence of any exogenous soluble factors, osteoblastic maturation of
      primary human osteoblasts (HOBs) but not osteoblastic differentiation of MSCs is
      strongly influenced by nanostructures superimposed onto a microrough Ti6Al4V
      (TiAlV) alloy. The sensitivity of osteoblasts to both surface microroughness and
      nanostructures led to a synergistic effect on maturation and local factor
      production. Osteoblastic differentiation of MSCs was sensitive to TiAlV surface
      microroughness with respect to production of differentiation markers, but no
      further enhancement was found when cultured on micro/nanostructured surfaces.
      Superposition of nanostructures to microroughened surfaces affected final MSC
      numbers and enhanced production of vascular endothelial growth factor (VEGF) but
      the magnitude of the response was lower than for HOB cultures. Our results
      suggest that the differentiation state of osteoblast-lineage cells determines the
      recognition of surface nanostructures and subsequent cell response, which has
      implications for clinical evaluation of new implant surface nanomodifications.

PMID- 22989385
TI  - Prevention of relative migration of the implant and the skin in murine model.

PMID- 22989386
TI  - Clinical coding of transnasal pituitary operations.

PMID- 22989387
TI  - W/O microemulsions as dendrimer nanocarriers: an EPR study.
AB  - A complex system, based on a dendrimer solubilized in the aqueous core of water
      in-oil microemulsion, may combine the advantages of both dendrimers and
      microemulsions to provide better control of drug release. We report for the first
      time the use of EPR technique to determine the effect of solubilized dendrimer on
      the structure of the microemulsion. The solubilized poly(propyleneimine) (PPI-G2)
      interacts with sodium bis(2-ethylhexyl) sulfosuccinate (AOT). EPR analysis
      provided information on polarity, microviscosity, and molecular order of the
      systems. Polarity and microviscosity increased from unloaded water-in-oil
      microemulsion to the system loaded with 0.2 wt % PPI-G2, but remained unchanged
      with higher PPI-G2 loads. The degree of order also increased with 0.2 wt % PPI-G2
      with only minor additional increase with larger quantities (25 wt %) of PPI-G2.
      Variations in pH only slightly affected the structure of microemulsion in the
      absence and presence of the loaded dendrimers. Aliphatic oils with longer
      lipophilic chains enhanced the structural order of the microemulsion. On
      increasing water content, polarity and degree of order increased. PPI-G2
      dendrimer in small loads is attracted by the negatively charged AOT and thus
      intercalates in the interface of the droplets. Yet, at higher PPI-G2 loads, the
      excess molecules are solubilized in the water core.

PMID- 22989388
TI  - World Stroke Day 2012: one in six.

PMID- 22989390
TI  - ASPECTaSaurus (a dinosaur)?
AB  - There is mounting evidence that shows how poorly non-contrast computed tomography
      (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) performs in the first
      three-hours after stroke onset compared to Diffusion weighted (DWI) magnetic
      resonance imaging (MRI). It is time to move into the 21st century and use more
      advanced imaging routinely in hyper-acute stroke assessment. While a useful tool
      if one is limited to NCCT alone, ASPECTS becomes somewhat superfluous as we now
      have rapid, validated, automated infarct core and penumbra volumes with either
      MRI or perfusion CT.

PMID- 22989391
TI  - Cerebral microbleeds: do they really predict macrobleeding?
AB  - There is growing evidence linking microbleeds to macrobleeding in selected
      patient populations. Yet, prospective data in unselected populations are scarce.
      The high prevalence of microbleeds and relatively low incidence of symptomatic
      intracerebral haemorrhage suggest that it may be a specific sub-group of persons
      with microbleeds developing macrobleeding. This may be related to the severity
      and nature of the underling vascular pathology. Future studies should therefore
      use a longitudinal design and not only focus on microbleed presence, but also on
      location and number of microbleeds.

PMID- 22989392
TI  - IST-3: a major contribution to thrombolysis research.

PMID- 22989393
TI  - IST-3: no pragmatic answers.

PMID- 22989394
TI  - The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program.
AB  - BACKGROUND: Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in
      phase III of clinical development. In comparison to alteplase, it has high fibrin
      selectivity, is associated with minimal or no neurotoxicity, and has no apparent
      negative effect on the blood-brain barrier. The safety and efficacy of
      desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke
      clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in
      Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in
      Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind,
      placebo-controlled, phase III trials are ongoing at >200 sites worldwide
      (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic
      Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo
      controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in
      Acute Ischemic Stroke-Japan, n = 48; DIAS-J). AIMS: The objective of DIAS-3 and
      DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of
      90 MUg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke
      (National Institutes of Health Stroke Scale 4-24, age 18-85 years). The objective
      of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90
      MUg/kg three- to nine-hours after ischemic stroke onset in Japanese patients.
      METHODS: Patients are included with occlusion or high-grade stenosis
      (thrombolysis in myocardial infarction 0-1) in proximal cerebral arteries on
      magnetic resonance or computed tomography angiography but excluded with extended
      ischemic edema on computed tomography or diffusion-weighted imaging. CONCLUSION:
      Desmoteplase is the only thrombolytic agent in late-stage development for acute
      ischemic stroke that is now tested in patients with proven stroke pathology. The
      results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will
      show whether patients with major artery occlusions but not extended ischemic
      brain damage can be safely and effectively treated up to nine-hours after onset.

PMID- 22989396
TI  - Enhanced carotid plaque on contrast-enhanced ultrasound is associated with plaque
      instability and rupture.

PMID- 22989395
TI  - Release of free fatty acids and interleukins from atherosclerotic plaques during
      carotid artery stenting.

PMID- 22989397
TI  - Effectiveness of thrombolysis in the Rhone region, France: a prospective
      population-based study.

PMID- 22989398
TI  - Low education as a predictor of poor one-year stroke survival in the EMMA Study
      (Study of Stroke Mortality and Morbidity in Adults), Brazil.

PMID- 22989399
TI  - Statins and cerebral perfusion in patients with leukoaraiosis--a translational
      proof-of-principal MRI study.

PMID- 22989400
TI  - Poor visual estimation of stroke patients' body weight by healthcare
      professionals has implications for stroke thrombolysis therapy.

PMID- 22989401
TI  - Association of PDE4D gene with ischaemic stroke.

PMID- 22989402
TI  - Recombinant tissue plasminogen activator (rtPA) and stroke unit for acute
      ischaemic stroke in developing countries, are they cost-effective?

PMID- 22989403
TI  - Evaluating health visitor assessments of mother-infant interactions: a mixed
      methods study.
AB  - BACKGROUND: Given the significance of reliably detecting cases where mother
      infant relationships are not developing successfully, it is important that
      initial assessment processes are as sensitive and specific as possible.
      OBJECTIVES: This study sought to examine the processes by which health visitors
      identify problems in mother-infant relationships in the post-natal period.
      DESIGN: Mixed methods. SETTINGS: Two universities and two primary care trusts.
      PARTICIPANT: In Phase One 17 first-time mothers and their 6- to 16-week-old
      infants were recruited. In Phase Two, a sample of 12 health visitors
      participated. METHODS: The study incorporated two data collection phases. In
      Phase One, each mother's interaction with her baby was video-recorded for 20min
      in an observation laboratory. The video-recordings were coded and resultant data
      were analysed to derive a number of quantitative measures of interaction quality,
      including mothers' responsiveness and sensitivity to their infants as rated by
      the Global Ratings Scales (GRS) of Mother-Infant Interaction. In Phase Two, 12
      health visitors rated and assessed 9 clips of the video-recorded mother-infant
      interactions. The rationales for their ratings were then explored through in
      depth interviews. Health visitor ratings of the video clips were compared to the
      GRS ratings. The relationship between the main focus of each health visitor
      rating, as reported in the interview, and the consistency of ratings with the GRS
      ratings were then investigated. RESULTS: Correlations between individual health
      visitors' ratings and the GRS ratings ranged from .17 to .83 and were
      statistically significant in only four cases. There was a weak relationship with
      health visitors' years of experience (r(s)=.47, NS). When explaining their
      judgements, health visitors tended to comment on the mother's behaviours or the
      relationship between the mother and baby and often ignored the behaviour of the
      baby. There was a highly significant relationship between the consistency of
      health visitor/GRS ratings and the number of references to the baby in the health
      visitors' explanations (r(s)=.75, p=.005). CONCLUSION: This study contributes to
      the understanding of how health visitors make assessments of mother-infant
      interactions. The frequent lack of attention and reference to the baby's
      behaviour suggests an area for further training.

PMID- 22989404
TI  - Determinants of moral distress in daily nursing practice: a cross sectional
      correlational questionnaire survey.
AB  - BACKGROUND: Moral distress is associated with job dissatisfaction, turnover and
      early retirement. Because of these negative consequences moral distress should be
      reduced. Little research has been done on what job factors contribute to whether
      or not a situation causes moral distress. OBJECTIVE: To identify individual and
      job characteristics associated with moral distress in nursing staff. DESIGN: This
      is a cross sectional correlational study. Nursing staff members completed two
      survey questionnaires with a time-interval of 3 months. In the first survey
      questions were asked about job characteristics and job satisfaction. Three months
      afterwards the respondents answered questions on moral distress. PARTICIPANTS:
      365 nursing staff members employed in nursing homes, homes for the elderly, home
      care and acute care hospitals completed both questionnaires. RESULTS: High moral
      distress levels were related to lower job satisfaction. Moral distress is higher
      when nurses perceive less time available to give care to patients. If
      satisfaction with the consultation possibilities within the team is low and when
      an instrumental leadership style exists, nursing staff members are also more
      likely to experience moral distress. Nursing staff members working 30-40h per
      week experience less moral distress than colleagues working fewer hours per week.
      Multivariate analyses showed no relations with other individual characteristics
      measured. CONCLUSION: Job characteristics that contribute to moral distress
      should be an issue for managers because it is related to job satisfaction.
      Interventions to reduce moral distress should target at organisational issues.
      The way a team is supported can raise or decrease moral distress levels.

PMID- 22989405
TI  - Assessment of internal condition of waste in a roofed landfill.
AB  - Recently, roofed landfills have been gaining popularity in Japan. Roofed
      landfills have several advantages over non-roofed landfills such as eliminating
      the visibility of waste and reducing the spread of offensive odours. This study
      examined the moisture balance and aeration conditions, which promote waste
      stabilisation, in a roofed landfill that included organic waste such as food
      waste. Moisture balance was estimated using waste characterization and the total
      amount of landfilled waste. Internal conditions were estimated based on the
      composition, flux, and temperature of the landfill gas. Finally, in situ aeration
      was performed to determine the integrity of the semi-aerobic structure of the
      landfill. With the effects of rainfall excluded, only 15% of the moisture held by
      the waste was discharged as leachate. The majority of the moisture remained in
      the waste layer, but was less than the optimal moisture level for biodegradation,
      indicating that an appropriate water spray should be administered. To assess
      waste degradation in this semi-aerobic landfill, the concentration and flow rate
      of landfill gas were measured and an in situ aeration test was performed. The
      results revealed that aerobic biodegradation had not occurred because of the
      unsatisfactory design and operation of the landfill.

PMID- 22989407
TI  - Exfoliated cells of the oral mucosa for HPV typing by SPF10 in head and neck
      cancer.
AB  - HPV infection in the superficial cells of the oral mucosa could reflect the
      presence of HPV in head and neck cancer cells. Due mostly to the use of
      heterogeneous analytical methods, discordant data exist in the literature
      regarding the agreement between the presence of HPV in non-neoplastic oral mucosa
      and in tumour tissue from the same patient. The presence of HPV DNA and viral
      types were compared in paired cytological and biopsy samples from 56 patients
      with head and neck neoplastic and preneoplastic lesions using the highly
      sensitive SPF10 LiPA Extra assay, which has been validated recently for formalin
      fixed paraffin-embedded tissue using paired cervical cytology and biopsy samples.
      Kappa statistics were used to measure the inter-rater agreement. The overall
      agreement with respect to HPV infection was 96.43% (kappa=0.8367). For 76.79% of
      subjects (kappa=0.6937), the same number of HPV types was detected in cytological
      and biopsy specimens. The overall positive typing agreement was 90.90%,
      comprising 130 out of 143 individual HPV type analyses. The agreement shown was
      good for HPV 18, 44, 45, 54 and 66 (kappa=0.6585-0. 7321), excellent for HPV 6,
      16, 40, and 54 (kappa=0.8108-0.8679), and absolute for HPV 11, 31, 33, 35, 39,
      51, 52, 53, 59, 74, and 69-71 (kappa=1.0000). The high sensitivity of the SPF10
      LiPA and its excellent performance both for recognising HPV infection and for
      identifying the viral types present in tumour tissue and in oral exfoliated cells
      make it a useful method for the assessment of HPV infection in patients with head
      and neck cancer. The excellent agreement for HPV infection and genotyping in
      paired samples suggests that oral exfoliated cells can be used for HPV detection
      in the head and neck region.

PMID- 22989406
TI  - Multifunctional protein APPL2 contributes to survival of human glioma cells.
AB  - Some endocytic proteins have recently been shown to play a role in tumorigenesis.
      In this study, we demonstrate that APPL2, an adapter protein with known endocytic
      functions, is upregulated in 40% cases of glioblastoma multiforme, the most
      common and aggressive cancer of the central nervous system. The silencing of
      APPL2 expression by small interfering RNAs (siRNAs) in glioma cells markedly
      reduces cell survival under conditions of low growth factor availability and
      enhances apoptosis (measured by executor caspase activity). Long-term depletion
      of APPL2 by short hairpin RNAs (shRNAs), under regular growth factor
      availability, suppresses the cell transformation abilities, assessed by inhibited
      colony formation in soft agar and by reduced xenograft tumor growth in vivo. At
      the molecular level, the negative effect of APPL2 knockdown on cell survival is
      not due to the alterations in AKT or GSK3beta activities which were reported to
      be modulated by APPL proteins. Instead, we attribute the reduced cell survival
      upon APPL2 depletion to the changes in gene expression, in particular to the
      upregulation of apoptosis-related genes, such as UNC5B (a proapoptotic dependence
      receptor) and HRK (harakiri, an activator of apoptosis, which antagonizes anti
      apoptotic function of Bcl2). In support of this notion, the loss of glioma cell
      survival upon APPL2 knockdown can be rescued either by an excess of netrin-1, the
      prosurvival ligand of UNC5B or by simultaneous silencing of HRK. Consistently,
      APPL2 overexpression reduces expression of HRK and caspase activation in cells
      treated with apoptosis inducers, resulting in the enhancement of cell viability.
      This prosurvival activity of APPL2 is independent of its endosomal localization.
      Cumulatively, our data indicate that a high level of APPL2 protein might enhance
      glioblastoma growth by maintaining low expression level of genes responsible for
      cell death induction.

PMID- 22989408
TI  - Quantitative analysis of four rapid antigen assays for detection of pandemic H1N1
      2009 compared with seasonal H1N1 and H3N2 influenza A viruses on nasopharyngeal
      aspirates from patients with influenza.
AB  - Data on analytical sensitivity of rapid diagnostic assays are important for
      clinical management of influenza, especially during a pandemic. Four rapid
      antigen detection assays were compared for detection of pandemic influenza A H1N1
      2009, seasonal H1N1 and H3N2 in 96 patients with influenza A infection confirmed
      by real-time RT-PCR. These rapid antigen tests appeared to have lower sensitivity
      (55.8%) for the diagnosis of pandemic influenza A H1N1 2009 as compared with
      seasonal H3N2 (71.0%) or H1N1 (69.4%) influenza infections, a difference that was
      related to a lower viral load in patients infected with the pandemic influenza A
      H1N1 2009 virus. The detection limit of these antigen detection tests in clinical
      specimens was an influenza A M gene copy number of average 1.0*10(7) copies/ml.
      Significant variations between tests in sensitivity for detection of pandemic
      influenza A H1N1 2009 (43.4-63.3%) were observed. The Directigen EZ Influenza A+B
      and the Espline Influenza A+B had comparable sensitivity (63%) and were the most
      sensitive among the four assays evaluated.

PMID- 22989409
TI  - Evaluation of five rapid diagnostic kits for influenza A/B virus.
AB  - Influenza viruses cause seasonal epidemics associated with high morbidity and
      mortality. However, even during periods of epidemic prevalence, clinical
      diagnoses are problematic. Rapid diagnostic tests for the detection of pandemic
      influenza A/B virus are valuable for their ease of use. Many rapid influenza
      diagnostic kits were introduced recently in the Republic of Korea (ROK),
      including Directizen EZ Flu A and B (Becton Dickinson, Sparks, USA), Binax Now
      Influenza A/B antigen kit (Binax, Portland, USA), Genedia influenza Ag (Green
      Cross, Yongin, ROK), Humasis Influenza A/B antigen test (Humasis, Anyang, ROK),
      and SD Bioline rapid influenza kit (Standard Diagnostics, Yongin, ROK). The
      objective of this study was to evaluate the performance of these five rapid
      diagnostic kits. The results were compared with those of viral culture and
      reverse transcription (RT)-PCR. A total of 253 nasopharyngeal swabs were analyzed
      from 253 patients (influenza A, n=67; B, n=86; negative samples, n=100). The
      specimens were tested immediately by conventional influenza virus culture and RT
      PCR, stored at -80 degrees C, and tested using five rapid test kits. The
      performance of the five rapid tests kits varied with sensitivities between 71.0
      and 82.1% and between 37.2 and 47.7% for detecting influenza A and B,
      respectively. For influenza A, the sensitivities of the Directizen EZ Flu A and
      B, Binax Now Influenza A/B antigen kit, Genedia influenza Ag, Humasis Influenza
      A/B antigen test, and SD Bioline rapid influenza kits were 82.1%, 71.0%, 76.1%,
      79.1%, and 82.1%, respectively; those for influenza B were 40.7%, 37.2%, 40.7%,
      41.8%, and 47.7%, respectively. The specificity of all rapid tests was 100%.
      Commercial influenza antigen detection assays are useful tools for the rapid
      diagnosis of influenza. However, confirmatory testing is always recommended.

PMID- 22989410
TI  - Similarities and differences between five European drug reimbursement systems.
AB  - OBJECTIVES: The aim of our study is to compare five European drug reimbursement
      systems, describe similarities and differences, and obtain insight into their
      strengths and weaknesses and formulate policy recommendations. METHODS: We used
      the analytical Hutton Framework to assess in detail drug reimbursement systems in
      Austria, Belgium, France, the Netherlands, and Sweden. We investigated policy
      documents, explored literature, and conducted fifty-seven interviews with
      relevant stakeholders. RESULTS: All systems aim to balance three main objectives:
      system sustainability, equity and quality of care. System impact, however, is
      mainly assessed by drug expenditure. A national reimbursement agency evaluates
      reimbursement requests on a case-by-case basis. The minister has discretionary
      power to alter the reimbursement advice in Belgium, France, and the Netherlands.
      All systems make efforts to increase transparency in the decision-making process
      but none uses formal hierarchical reimbursement criteria nor applies a cost
      effectiveness threshold value. Policies to deal with uncertainty vary: financial
      risk-sharing by price/volume contracts (France, Belgium) versus coverage with
      evidence development (Sweden, the Netherlands). Although case-by-case revisions
      are embedded in some systems for specific groups of drugs, systematic (group)
      revisions are limited. CONCLUSIONS: As shared strengths, all systems have clear
      objectives reflected in reimbursement criteria and all are prepared to pay for
      drugs with sufficient added value. However, all systems could improve the
      transparency of the decision-making process; especially appraisal lacks
      transparency. Systems could increase the use of (systematic) revisions and could
      make better use of HTA (among others cost-effectiveness) to obtain value for
      money and ensure system sustainability.

PMID- 22989412
TI  - Sleep-dependency of episodic-like memory consolidation in rats.
AB  - Episodic memory refers to the recollection of a representation that binds
      together into a unique past experience "what" happened, "where" and "when". Sleep
      has been identified as a state that optimizes the consolidation of newly acquired
      memory. To determine if sleep is important for the consolidation of episodic-like
      memory, we tested rats on an episodic-like memory task requiring the binding of
      an object memory into a spatio-temporal context, as well as retention of its
      individual components, using separate tests of novel-object recognition ("what"),
      object-place recognition ("where") and temporal memory ("when"), respectively.
      The 80-min retention interval between encoding of the task and retrieval testing
      covered either a period of regular morning sleep or sleep deprivation or a period
      of evening wakefulness. Sleep during the retention interval, compared with the
      other two retention conditions, significantly enhanced retrieval in the episodic
      like memory task as well as in the object-place recognition and temporal memory
      tasks. In fact, when the rats stayed awake during the retention interval, there
      was no significant memory left at retrieval testing for the learnt object place
      and temporal memory. Sleep did not benefit novel-object recognition memory which
      unlike the other components of episodic-like memory is considered not to
      critically rely on the hippocampus. In an additional delayed sleep condition,
      episodic-like memory in rats which had stayed awake during the first 80-min
      interval after encoding, was not recovered when they were allowed to sleep during
      a subsequent 80-min interval. Our results suggest that sleep specifically
      supports the aspects in episodic memory most closely linked to hippocampal
      function, i.e., the binding of an event into spatio-temporal context as well as
      the spatio-temporal context itself. Sleep is particularly effective when it
      occurs shortly after encoding.

PMID- 22989411
TI  - Small-molecule inhibition of MLL activity by disruption of its interaction with
      WDR5.
AB  - WDR5 (WD40 repeat protein 5) is an essential component of the human trithorax
      like family of SET1 [Su(var)3-9 enhancer-of-zeste trithorax 1] methyltransferase
      complexes that carry out trimethylation of histone 3 Lys4 (H3K4me3), play key
      roles in development and are abnormally expressed in many cancers. In the present
      study, we show that the interaction between WDR5 and peptides from the catalytic
      domain of MLL (mixed-lineage leukaemia protein) (KMT2) can be antagonized with a
      small molecule. Structural and biophysical analysis show that this antagonist
      binds in the WDR5 peptide-binding pocket with a Kd of 450 nM and inhibits the
      catalytic activity of the MLL core complex in vitro. The degree of inhibition was
      enhanced at lower protein concentrations consistent with a role for WDR5 in
      directly stabilizing the MLL multiprotein complex. Our data demonstrate
      inhibition of an important protein-protein interaction and form the basis for
      further development of inhibitors of WDR5-dependent enzymes implicated in MLL
      rearranged leukaemias or other cancers.

PMID- 22989413
TI  - Intracerebroventricular injection of orexin-2 receptor antagonist promotes REM
      sleep.
AB  - Orexins are important regulators of sleep-wakefulness (S-W). Rats were
      intracerebroventricularly (ICV) administered selective orexin-2 receptor
      antagonist, TCS-OX2-29. There was decreased wakefulness due to a decrease in the
      average wake episode duration and an increased REM sleep due to an increase in
      the number of REM episodes, indicating an inhibitory role of the central orexin-2
      receptors on REM sleep generation.

PMID- 22989414
TI  - Withaferin A-stimulated Ca2+ entry, ceramide formation and suicidal death of
      erythrocytes.
AB  - Withaferin A, a triterpenoid component from Withania somnifera, counteracts
      malignancy, an effect attributed to stimulation of apoptosis. Withaferin A is
      partially effective through induction of oxidative stress, altered gene
      expression and mitochondrial depolarization. Erythrocytes lack mitochondria and
      nuclei but may enter apoptosis-like eryptosis, a suicidal cell death
      characterized by cell shrinkage and cell membrane scrambling with
      phosphatidylserine exposure at the cell surface. Triggers of eryptosis include
      increase of cytosolic Ca(2+)-activity [Ca(2+)](i) following activation of oxidant
      sensitive Ca(2+)-permeable cation channels, ceramide formation and/or ATP
      depletion. The present study explored, whether withaferin A triggers eryptosis.
      To this end, [Ca(2+)](i) was estimated from Fluo3-fluorescence, cell volume from
      forward scatter, phosphatidylserine exposure from annexin-V-binding, hemolysis
      from hemoglobin release, oxidative stress from DCFDA-fluorescence and ceramide
      abundance utilizing antibodies. A 48 h exposure to withaferin A significantly
      decreased forward scatter (at >= 10 MUM withaferin concentration) and increased
      [Ca(2+)](i) (>= 5 MUM), ROS-formation (>= 10 MUM) ceramide-formation ( >= 10 MUM)
      as well as annexin-V-binding ( >= 5 MUM). Withaferin A treatment was followed by
      slight but significant increase of hemolysis. Extracellular Ca(2+) removal,
      amiloride, and the antioxidant N-acetyl-l-cysteine significantly blunted
      withaferin A-triggered annexin-V-binding. The present observations reveal that
      withaferin A triggers suicidal erythrocyte death despite the absence of gene
      expression and key elements of apoptosis such as mitochondria.

PMID- 22989415
TI  - Dr George Home: Royal Australasian College of Surgeons Fellow 169.
AB  - George Home was Fellow number 169 of the Royal Australasian College of Surgeons.
      He was born in San Francisco in 1870, coming to New Zealand as an infant. He
      overcame the early death of his father to excel at school and graduate top of his
      class at the University of Edinburgh in 1892. During his time in Edinburgh, he
      was taught by Lord Lister and developed a lifelong interest in surgical asepsis
      and antisepsis. After working in Liverpool for five years, he returned to New
      Zealand and commenced practice as a surgeon in New Plymouth in 1899. He remained
      in New Plymouth for the remainder of his life, although served with distinction
      in World War I and was the longest serving New Zealand medical officer in the
      Gallipoli Campaign. Upon his return to New Zealand after World War I, he founded
      and developed many community institutions and was a noted amateur alpinist,
      photographer and botanist. He died in 1956 after a lifetime dominated, not by one
      single achievement, but by much service to his community.

PMID- 22989416
TI  - Headless compression screw fixation of jones fractures: an outcomes study in
      Japanese athletes.
AB  - BACKGROUND: Internal fixation is advocated as the primary treatment for fifth
      metatarsal Jones fractures in athletes; however, screw insertion site discomfort
      and refracture can occur especially in competitive athletes. The ideal implant
      has not been determined. HYPOTHESIS: Headless compression screw fixation of
      proximal fifth metatarsal Jones fractures is an effective treatment approach
      especially in competitive athletes. STUDY DESIGN: Case series; Evidence level, 4.
      METHODS: We studied 60 athletes treated surgically with a headless compression
      screw for fifth metatarsal Jones fractures (mean age, 19 years). The mean follow
      up time was 178 weeks. We evaluated the clinical and radiographic outcomes of
      headless compression screw fixation of Jones fractures. RESULTS: All athletes
      returned to full activity. The mean time to start running after surgery was 6.3
      weeks (range, 3-12.7 weeks), and the mean time to full activity after surgery was
      11.2 weeks (range, 6-25 weeks). One athlete suffered a delayed union, which
      healed uneventfully. One athlete suffered a nonunion and underwent reoperation
      for a screw exchange to an autogenous bone graft harvested from the iliac crest.
      No screw breakage was reported. No athlete suffered a refracture or discomfort in
      the screw insertion site. CONCLUSION: Headless compression screw fixation of
      fifth metatarsal Jones fractures provided excellent results, allowing athletes to
      return to full activity without both screw insertion site irritation and clinical
      refracture.

PMID- 22989417
TI  - Comparative analysis of Shigella sonnei biotype g isolated from paediatric
      populations in Egypt, 1999-2005.
AB  - Strain characteristics of 51 Shigella sonnei isolates obtained from children
      seeking medical care (MC) and 48 isolates recovered during a prospective
      diarrhoea birth cohort (BC) study were compared. Biochemical characterization and
      antibiotic susceptibility testing determined that all S. sonnei isolates were
      biotype g and multidrug-resistant. Plasmid profiling identified 15 closely
      related patterns and XbaI pulsed-field gel electrophoresis confirmed the high
      degree of genetic similarity between isolates. All S. sonnei isolates harboured
      ipaH and class II integrase genes and 84?3 and 80% of the MC and BC isolates,
      respectively carried the sen gene. Neither the class I integrase nor the set gene
      was detected. Our results indicate that S. sonnei isolates associated with severe
      diarrhoea were indistinguishable from those associated with mild diarrhoea.
      Additional genetic tests with greater discrimination might offer an opportunity
      to determine genetic differences within the globally disseminating biotype g
      clone.

PMID- 22989418
TI  - The response of mental health services to domestic violence: a qualitative study
      of service users' and professionals' experiences.
AB  - PURPOSE: Despite numerous policies advocating for routine enquiry of abuse by
      mental health professionals, it is not known if such enquiry is acceptable to
      service users and clinicians. Furthermore, limited evidence exists on clinicians'
      response to domestic violence. This study aims to explore the acceptability of
      routine enquiry and experiences of responding to domestic violence from service
      user and professional perspectives. METHODS: A qualitative study design was used
      to conduct individual interviews with a purposive sample of community mental
      health service users (n = 24) and professionals (n = 25). Thematic analysis was
      employed to establish superordinate and subordinate themes, which were
      transformed into conceptual maps. RESULTS: All service users considered routine
      enquiry about domestic violence in mental health settings to be acceptable but a
      small minority of professionals did not. Service users described positive
      experiences of help seeking, including receiving acknowledgement for the abuse
      and support for their multiple needs, and negative experiences, including
      nonvalidating responses from clinicians following disclosure, discrimination, and
      an absence of support from services. Main themes for professionals included
      difficulties in assessment and management of domestic violence, reporting
      requirements, and unclear referral pathways. CONCLUSIONS: To respond to the needs
      of mental health service users experiencing domestic violence, services need to
      articulate a clear care and referral pathway.

PMID- 22989419
TI  - Targeting protein tyrosine kinase 6 enhances apoptosis of colon cancer cells
      following DNA damage.
AB  - Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that has
      distinct functions in normal epithelia and cancer. It is expressed primarily in
      nondividing epithelial cells in the normal intestine, where it promotes
      differentiation. However, after DNA damage, PTK6 is induced in proliferating
      progenitor cells, where it contributes to apoptosis. We examined links between
      PTK6 and the tumor suppressor p53 in the isogenic p53(+/+) and p53(-/-) HCT116
      colon tumor cell lines. We found that p53 promotes expression of PTK6 in HCT116
      cells, and short hairpin RNA-mediated knockdown of PTK6 leads to reduced
      induction of the cyclin-dependent kinase inhibitor p21. Knockdown of PTK6
      enhances apoptosis in HCT116 cells with wild-type p53, following treatment of
      cells with gamma-radiation, doxorubicin, or 5-fluorouracil. No differences in the
      activation of AKT, ERK1/2, or ERK5, known PTK6-regulated prosurvival signaling
      proteins, were detected. However, activity of STAT3, a PTK6 substrate, was
      impaired in cells with knockdown of PTK6 following DNA damage. In contrast to its
      role in the normal epithelium following DNA damage, PTK6 promotes survival of
      cancer cells with wild-type p53 by promoting p21 expression and STAT3 activation.
      Targeting PTK6 in combination with use of chemotherapeutic drugs or radiation may
      enhance death of colon tumor cells with wild-type p53.

PMID- 22989420
TI  - Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of
      small cell lung cancer cells through the downregulation of the NF-kappaB
      activity.
AB  - Notch signaling regulates cell-fate decisions during development and postnatal
      life. Little is known, however, about the role of Delta-like-4 (Dll4)-Notch
      signaling between cancer cells, or how this signaling affects cancer metastasis.
      We, therefore, assessed the role of Dll4-Notch signaling in cancer metastasis. We
      generated a soluble Dll4 fused to the IgG1 constant region (Dll4-Fc) that acts as
      a blocker of Dll4-Notch signaling and introduced it into human small cell lung
      cancer (SCLC) cell lines expressing either high levels (SBC-3 and H1048) or low
      levels (SBC-5) of Dll4. The effects of Dll4-Fc on metastasis of SCLC were
      evaluated using a mouse model. Although Dll4-Fc had no effect on the liver
      metastasis of SBC-5, the number of liver metastasis inoculated with SBC-3 and
      H1048 cells expressing Dll4-Fc was significantly lower than that injected with
      control cells. To study the molecular mechanisms of the effects of Dll4-Fc on
      liver metastasis, a PCR array analysis was conducted. Because the expression of
      NF-kappaB target genes was affected by Dll4-Fc, we conducted an electrophoretic
      mobility shift assay and observed that NF-kappaB activities, both with and
      without stimulation by TNF-alpha, were downregulated in Dll4-Fc-overexpressing
      SBC-3 and H1048 cells compared with control cells. Moreover, Dll4-Fc attenuates,
      at least in part, the classical and alternative NF-kappaB activation pathway by
      reducing Notch1 signaling. These results suggest that Dll4-Notch signaling in
      cancer cells plays a critical role in liver metastasis of SCLC by regulating NF
      kappaB signaling.

PMID- 22989421
TI  - Chronic urticaria following acute hepatitis A.
AB  - Urticaria has a documented association with the prodromal phases of hepatitis A,
      B and, although still contentious, likely hepatitis C. Despite the documented
      association there are few actual reported cases of urticaria occurring with
      hepatitis A infection and in all of the cases reported so far the urticaria
      preceded the diagnosis of hepatitis A and was acute rather than chronic. We
      describe a case of urticaria occurring following acute infection with hepatitis
      A, which persisted beyond 6 weeks and therefore was by definition chronic.
      Although chronic urticaria has been reported to be associated with other forms of
      viral hepatitis, to the best of our knowledge this has not been reported
      previously with hepatitis A.

PMID- 22989422
TI  - Williams-Campbell syndrome presenting in an adult.
AB  - A 59-year-old man presented with a 4-year history of productive cough, shortness
      of breath and wheeze. He had been treated for asthma and given several courses of
      antibiotics which improved his symptoms. Medical history was unremarkable. There
      was no history respiratory disease in childhood although he was prone to chest
      infections in adult life. A high-resolution chest CT showed marked proximal
      cystic bronchiectasis associated with collapse of distal bronchi on expiration. A
      diagnosis of cystic bronchiectasis due to undiagnosed adult Williams-Campbell
      syndrome was made on the basis of these characteristic radiological features and
      the exclusion of other possible causes.

PMID- 22989423
TI  - Determination of nine environmental phenols in urine by ultra-high-performance
      liquid chromatography-tandem mass spectrometry.
AB  - A method was developed to determine nine environmental phenols, including
      bisphenol A, 2,3,4-trichlorophenol, 2,4,5-trichlorophenol, pentachlorophenol,
      triclosan (2,4,4'-trichloro-2'-hydroxyphenylether), 4-tert-octylphenol, 4-n
      octylphenol, 4-n-nolyphenol and benzophenone-3 (2-hydroxy-4-methoxybenzophenone)
      in human urine using ultra-high-performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS-MS). The analytes were extracted and preconcentrated with
      solid-phase extraction, and then quantified with UPLC-electrospray ionization
      (negative ion mode)-MS-MS using multiple reaction monitoring mode. Limits of
      detection of the nine phenols ranged from 0.02 to 0.90 ng/mL. This method was
      further validated by the determination of phenols in 325 human urine samples that
      generated data regarding the exposure of various phenols to Chinese adults
      without occupational exposure to phenols.

PMID- 22989424
TI  - An efficient sample preparation method for high-throughput analysis of 15(S)-8
      iso-PGF2alpha in plasma and urine by enzyme immunoassay.
AB  - Although several methods have been reported on the analysis of the oxidative
      stress marker 15(S)-8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha) in biological
      fluids, they either involve extensive sample preparation and costly technology or
      require high sample volume. This study presents a sample preparation method that
      utilizes low sample volume for 8-iso-PGF2alpha analysis in plasma and urine by an
      enzyme immunoassay (EIA). In brief, 8-iso-PGF2alpha in deproteinized plasma or
      native urine sample is complexed with an antibody and then captured by molecular
      weight cut-off filtration. This method was compared with two other sample
      preparation methods that are typically used in the analysis of 8-iso-PGF2alpha by
      EIA: Cayman's affinity column purification method and solid-phase extraction on C
      18. The immunoaffinity purification method described here was superior to the
      other two sample preparation methods and yielded recovery values of 99.8 and
      54.1% for 8-iso-PGF2alpha in plasma and urine, respectively. Analytical precision
      (relative standard deviation) was +/-5% for plasma and +/-15% for urine. The
      analysis of healthy human plasma and urine resulted in basal 8-iso-PGF2alpha
      levels of 31.8 +/- 5.5 pg/mL and 2.9 +/- 2.0 ng/mg creatinine, respectively. The
      robustness and analytical performance of this method makes it a promising tool
      for high-throughput screening of biological samples for 8-iso-PGF2alpha.

PMID- 22989425
TI  - Hospital admissions associated with gout and their comorbidities in New Zealand
      and England 1999-2009.
AB  - OBJECTIVES: To describe the national demographics, comorbidities and mortality of
      admissions associated with gout in New Zealand (NZ) from 1999 to 2009 and compare
      this with English gout admission data from the same period. METHODS: The
      characteristics of all admissions due to or complicated by gout in NZ from 1999
      to 2009 were analysed. These findings were then compared with the wider NZ
      population and the English National Health Service (NHS) gout admission rates
      from 1999 to 2009. RESULTS: There were 10 241 admissions due to gout (group A)
      and 34 318 admissions complicated by gout (group B) in NZ from 1999 to 2009.
      There were 32 741 admissions due to gout in England over the same period. Gout
      admissions rose at 5.5% per year in NZ and at 7.2% per year in England over the
      study period. NZ gout patients admitted to hospital were more likely to be Maori
      or a Pacific Islander and had 3-7 comorbidities. Multiple admissions were common
      with 1479 NZ gout patients admitted more than once. Comorbidities varied between
      the NZ groups A and B: hypertension (19-39%), renal disease (16-27%) and diabetes
      mellitus (20-27%) were common. Heart failure (27.6%) and cardiovascular disease
      (39.1%) were common in those who had gout complicating their hospital admission.
      This group also had poorer survival compared with those admitted primarily for
      gout. CONCLUSION: This is the first study to describe the epidemiology of
      admissions associated with gout across an entire country. Admissions are rising
      in both countries studied and those admitted in NZ have a high rate of
      comorbidity and re-admission.

PMID- 22989426
TI  - Obesity and psoriatic arthritis: from pathogenesis to clinical outcome and
      management.
AB  - PsA is an axial and/or peripheral inflammatory arthritis associated with
      psoriasis, included in the group of spondylarthritides. It has been suggested
      that PsA could be a systemic disease, involving even coronary arteries and the
      heart. An increased prevalence of vascular risk factors has been found in PsA
      subjects as compared with the general population and psoriatic subjects.
      Moreover, PsA patients exhibit an increased prevalence of liver steatosis, a
      marker of metabolic syndrome, and of obesity. Interestingly, many reports
      demonstrate that adipose tissue is metabolically active, representing a source of
      inflammatory mediators, known as adipokines. The latter include TNF-alpha,
      macrophage chemoattractant protein-1, plasminogen activator inhibitor-1 (PAI-1),
      IL-6, leptin and adiponectin, leading to a pro-inflammatory status in obese
      subjects. This evidence supports the idea of obesity as a low-grade inflammatory
      disease. Accordingly, obesity might be associated with some rheumatic diseases.
      In particular, it seems to affect several features of PsA, such as its
      development, cardiovascular risk and clinical outcome. Recent data suggest that
      increased BMI in early adulthood increases the risk of PsA development in
      psoriatic patients, supporting a link between fat-mediated inflammation and joint
      involvement. Obesity may represent an additive cardio-metabolic risk factor in
      PsA subjects. Abdominal obesity may also determine an increased risk of not
      achieving minimal disease activity in PsA patients, highlighting the role of
      abdominal fat accumulation as a negative predictor of good clinical response to
      biologic agents. This review assesses the relationship between obesity and PsA
      according to the available literature.

PMID- 22989427
TI  - Personal protective equipment, hygiene behaviours and occupational risk of
      illness after July 2011 flood in Copenhagen, Denmark.
AB  - Incidence of various diseases can increase following a flood. We aimed to
      identify professionals in Copenhagen who became ill after contact with 2 July
      2011 floodwater/sediment and determine risks and protective factors associated
      with illness. We conducted a cohort study of employees engaged in post-flood
      management activities. Participants completed a questionnaire collecting
      information about demographics, floodwater/sediment exposure, compliance with
      standard precautions, and symptoms of illness. Overall, 257 professionals
      participated, with 56 (22%) cases. Risk of illness was associated with not
      washing hands after floodwater/sediment contact [relative risk (RR) 2?45],
      exposure to floodwater at work and home (RR 2?35), smoking (RR 1?92), direct
      contact with floodwater (RR 1?86), and eating/drinking when in contact with
      floodwater (RR 1?77). Professionals need to follow standard precautions when in
      contact with floodwater/sediment, especially proper hand hygiene after personal
      protective equipment use and before eating/drinking and smoking.

PMID- 22989429
TI  - Carotid artery compression by the hyoid bone.
AB  - An 83-year-old male presented with bilateral carotid stenosis. Stenosis on the
      left side was reported to be greater than 70%. A left carotid endarterectomy was
      undertaken to increase the lumen size and remove the atherosclerotic plaque.
      During surgery, the hyoid bone was observed to have a 2-cm calcified horn capable
      of compressing the carotid artery. This unusual compression was confirmed by
      radiographic images. In cases where the carotid artery is compressed by the hyoid
      bone, a carotid endarterectomy rather than a stent may be the procedure of
      choice.

PMID- 22989430
TI  - Noninvasive respiratory support in neonates: a brief review.
AB  - In the era of gentle ventilation and open lung strategy noninvasive ventilatory
      support in neonates has gained momentum and its use in nurseries around the world
      is also increased. This paper reviews various modalities of non-invasive
      respiratory support in some details and its relevance in the recent evidence
      based use. Continuous positive airway pressure (CPAP) is a mode of ventilatory
      assistance in which positive pressure is delivered to the airway throughout the
      respiratory cycle. It is also referred to as continuous distending pressure (CDP)
      or positive end expiratory pressure (PEEP) when applied through a ventilator
      along with intermittent mandatory ventilation (IMV). It has been proven over the
      years to be an effective mode of ventilatory support and as such has gained
      widespread use in the management of a variety of neonatal respiratory diseases.
      It is relatively cheap and easy to apply and certainly feasible for routine use
      in underdeveloped world. Besides improving oxygenation CPAP often functions as an
      airway stabilizer of the trachea thus helping to decrease the frequency of
      neonatal apneas, particularly the obstructive variety. There is good to fair
      quality supportive evidence from several studies that the use of primary CPAP can
      reduce the need for intubation and mechanical ventilation in infants less than 32
      weeks gestation. In this review, we will attempt to describe different delivery
      devices and pressure generating systems and discuss different ways in which CPAP
      can be applied. Although it is unclear that primary use of CPAP can reduce
      overall neonatal mortality and morbidity it is becoming increasingly clear that
      early CPAP use is less invasive, baby friendly and decreases the need and
      frequency of the use of surfactants. Besides, clinical indications for CPAP, its
      advantages and limitations will also be explored. CPAP adjuncts such as nasal
      intermittent positive pressure ventilation (NIPPV) and infant flow driver will
      also be discussed.

PMID- 22989428
TI  - Clinical significance of the clopidogrel-proton pump inhibitor interaction after
      peripheral endovascular intervention for claudication.
AB  - OBJECTIVE: Despite numerous studies in the cardiology literature, the clinical
      impact of proton pump inhibitor (PPI) administration on the antiplatelet effect
      of clopidogrel remains controversial. The objective of this study is to evaluate
      the effects of concurrent PPI and clopidogrel administration on outcomes after
      percutaneous transluminal angioplasty and stenting (PTA&S) of the superficial
      femoral artery (SFA) for claudication. METHODS: Retrospective review of a
      prospectively maintained database (2004-2010) identified patients undergoing
      PTA&S of the SFA for lifestyle-limiting claudication (Rutherford Class III).
      Statistical analysis included univariate comparison (Wilcoxon, chi-square) of
      demographics, lesion characteristics, complication rates, and outcome measures.
      Patency comparisons were made with Cox-PH multivariable models and Kaplan-Meier
      survival analysis. RESULTS: Totally, 109 limbs were treated in 103 patients. All
      were prescribed clopidogrel for 1 month; concurrent PPI use (+PPI) was identified
      after 42 (38.5%) interventions. There were no statistically significant
      differences in demographics, comorbidity prevalence, lesion length, degree of
      stenosis, or runoff associated with PPI use. There were no cases of early
      thrombosis in either group. There were more instances of patency loss (28 [50%]
      vs 21 [42%]; P = .40) in patients with +PPI, and a trend toward reduced primary
      patency that did not achieve statistical significance (P = .5). By multivariate
      analysis only TransAtlantic Inter-Society Consensus (TASC) D lesions were
      independent predictors of primary (hazards ratio [HR] = 4.366; [95% confidence
      interval (CI): 1.291-14.764; P = .018) and assisted patency loss (HR = 6.815
      [1.181-39.327]; P = .032). CONCLUSIONS: The clinical significance of the
      clopidogrel-PPI interaction is a controversial topic that has been the subject of
      numerous studies in the cardiology literature. This is the first report to
      examine this medication interaction after peripheral intervention. While there is
      no apparent association between PPI coadministration with clopidogrel in this
      series, the high prevalence of PPI use among patients prescribed clopidogrel
      following peripheral intervention warrants ongoing attention to this purported
      medication interaction.

PMID- 22989431
TI  - [Serum osteoprotegerin level in children with nephrotic syndrome and the effect
      of glucocorticoid on it].
AB  - OBJECTIVE: To observe serum osteoprotegerin (OPG) level in children with
      nephrotic syndrome (NS) and changes in serum OPG level after glucocorticoid
      therapy, with the aim of studying the role of OPG in the bone metabolism of
      children with NS. METHODS: Forty-four children with idiopathic NS were randomly
      selected as the study group, including 24 newly diagnosed, untreated patients and
      20 who had relapsed during the process of glucocorticoid reduction (cumulative
      dose of glucocorticoid 28327+/-5879 mg/m2). Twenty-three age- and sex-matched
      healthy children served as the control group. Serum osteoprotegerin (OPG) level
      was measured using ELISA. Serum N-terminal midfragment of osteocalcin (N-MID
      osteocalcin) was determined using electrochemical luminescence immunoassays
      (ECLIA). RESULTS: Serum levels of OPG (211+/-55 ng/L) and N-MID osteocalcin (46+/
      14 ng/mL) in the untreated NS group were reduced compared with 470+/-57 ng/L
      (OPG) and 73+/-9 ng/ml (N-MID osteocalcin) in the control group (P<0.05). Serum
      levels of OPG (176+/-42 ng/L) and N-MID osteocalcin (29+/-10 ng/mL) in the NS
      relapsed group were lower than in the untreated NS and control groups (P<0.05).
      CONCLUSIONS: Bone metabolism disorders are found in children with NS. High-doses
      of glucocorticoid therapy can aggravate these disorders. Serum OPG levels in
      children with NS may be affected by both the renal disease itself and steroid
      therapy, suggesting that OPG is expected to become a new biochemical indicator
      for predicting changes to the bone metabolism of children with NS.

PMID- 22989432
TI  - [Spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic
      syndrome complicated by urinary tract infection: an analysis of 97 cases].
AB  - OBJECTIVE: To investigate the spectrum and drug sensitivity of pathogenic
      bacteria in children with nephrotic syndrome (NS) complicated by urinary tract
      infection (UTI). METHODS: A retrospective analysis was performed on the spectrum
      and drug sensitivity of pathogenic bacteria in 97 children with NS complicated by
      UTI, who hospitalized from January to December, 2011. RESULTS: The incidence of
      UTI in children with NS was 36.5%. It was significantly more common in children
      with recurrent NS than in those with primary NS (44.0% vs 31.9%; P<0.05). These
      cases mainly presented with asymptomatic bacteriuria. Enterococcus was the most
      common pathogenic bacteria (50.5%), including Enterococcus faecium (29.4%) and
      Enterococcus faecalis (21.1%), followed by Gram-negative bacteria, such as
      Escherichia coli (15.6%) and Klebsiella pneumoniae (14.7%). Enterococcus was
      highly sensitive to nitrofurantoin, vacomycin and linezolid, but was highly
      resistant to tetracycline and moxifloxacin. More multi-resistant strains were
      detected in Enterococcus faecium than in Enterococcus faecalis (72% vs 17%;
      P<0.05). Escherichia coli and Klebsiella pneumoniae were highly sensitive to
      amikacin, imipenem and piperacillin/tazobactam. Of the Gram-negative bacteria,
      25% produced extended spectrum beta-lactamases (ESBLs). ESBLs-producing bacteria
      had 100% sensitivity to imipenem, amikacin and piperacillin/tazobactam but were
      highly resistant to ampicillin, cefazolin and ceftriaxone. CONCLUSIONS: Children
      with recurrent NS are more susceptible to UTI than those with primary NS.
      Enterococcus is becoming major pathogenic bacteria for UTI in children with NS
      and has relatively high drug resistance, and most strains of Enterococcus faecium
      are multi-resistant.

PMID- 22989433
TI  - [Effect of chorioamnionitis on brain injury in preterm infants].
AB  - OBJECTIVE: To explore the association between chorioamnionitis and brain injury
      in preterm infants. METHODS: A total of 88 preterm infants (28-34 weeks), who
      were born between June 2008 and June 2011, were divided into a case group (n=41)
      and a control group (n=47) according to whether or not they had chorioamnionitis.
      All the infants were examined by brain ultrasonography periodically after birth
      and underwent brain diffusion weighted imaging (DWI) between 3 and 7 days after
      birth. The two groups were compared in terms of the incidence of periventricular
      leukomalacia (PVL) and periventricular and intraventricular hemorrhage (PVH-IVH)
      by brain magnetic resonance imaging (MRI) at the corrected gestational age of 40
      weeks. RESULTS: There was statistical significance in the incidence of PVL
      between the case and the control groups (32% vs 6%; P<0.05), but no significant
      difference in the incidence of PVH-IVH between the two groups (27% vs 23%;
      P>0.05). CONCLUSIONS: Chorioamnionitis is associated with brain injury in preterm
      infants, increasing the incidence of PVL but having little influence over the
      incidence of PVH-IVH.

PMID- 22989434
TI  - [Predictive indices for critical condition for infants and young children with
      severe pneumonia].
AB  - OBJECTIVE: To investigate the early predictive indices of critical condition in
      infants and young children with severe pneumonia, and to provide reference for
      diagnosis and treatment of the disease. METHODS: Clinical data were collected on
      411 patients (aged 1-36 months) with severe pneumonia who were admitted from
      January 2009 to December 2011, and multivariate logistic regression analysis was
      performed using 23 potential indices. These cases were divided into a critical
      group of 139 cases who died in hospital or needed rescue or mechanical
      ventilation during the course of disease and an ordinary group of 411 cases.
      RESULTS: Eight indices with statistical significance were selected to predict the
      critical condition after multivariate logistic regression analysis, including
      hypocalcemia with the highest odds ratio (OR) (11.488), followed by sinus
      tachycardia (7.506), congenital heart disease (5.977), brain disorder symptoms
      (5.182), premature birth (4.978), blood potassium abnormality (2.910), metabolic
      acidosis (2.489) and malnutrition (2.048). CONCLUSIONS: The predictive indices of
      critical condition in infants and young children with severe pneumonia are
      hypocalcemia, sinus tachycardia, congenital heart disease, brain disorder
      symptoms, premature birth, blood potassium abnormality, metabolic acidosis and
      malnutrition. The infants and young children with these risk factors need
      intensive care.

PMID- 22989435
TI  - [Causes of chronic cough in children].
AB  - OBJECTIVE: To study the causes of chronic cough in children. METHODS:
      Retrospective analysis was carried out on the clinical data of 132 children with
      chronic cough from August 2010 to September 2011. RESULTS: Several conditions
      were found to contribute to chronic cough in children, including cough variant
      asthma (CVA, n=56), upper airway cough syndrome (UACS, n=44),
      infections/postinfectious cough (IC/PIC, n=22), allergic cough (AC, n=8),
      gastroesophageal reflux cough (GERC, n=5), and others (n=3). There was
      significant difference in the distribution of IC/IPC among an infant group (<1
      year), a group of young children (>1 year), a group of preschool aged children
      (>3 years) and a group of school-age children (6-14 years) (chi2=11.638,
      P=0.001), and the infant group showed a significantly higher prevalence of IC/PIC
      than the other three age groups (P<0.05). IC/PIC was the main cause of chronic
      cough in the infant group, while CVA and UACS were the main causes in each of the
      other groups. A relatively large proportion of AC, CVA and UACS cases had a
      personal history of allergy, a family history of allergy/asthma and a history of
      exposure to harmful environments. CONCLUSIONS: CVA, UACS, and IC/PIC are main
      causes of chronic cough in children, varying among different age groups. Children
      with a personal history of allergy, family history of allergy/asthma and a
      history of exposure to harmful environment are more vulnerable to AC, CVA and
      UACS.

PMID- 22989436
TI  - [Causes of stopping subcutaneous specific immunotherapy in asthmatic children].
AB  - OBJECTIVE: To improve the compliance with subcutaneous specific immunotherapy
      (SCIT) by analyzing the causes of stopping SCIT in asthmatic children. METHODS: A
      telephone follow-up was conducted in the asthmatic children who received SCIT but
      did not finished the 3-year course of treatment from June 2005 to October 2010,
      so as to analyze the causes of stopping SCIT. RESULTS: A total of 616 asthmatic
      children received SCIT, and 322 (52.2%) of them stopped SCIT.A total of 127 cases
      (39.4%) of the 322 children received telephone follow-up. In the 127 children, 53
      (41.8%) stopped the SCIT for the reason of bad effecacy, 29 (22.8%) for remission
      of asthma,12 (9.4%) for expensive fees, 10 (7.9%) for complex process of
      treatment, 10 (7.9%) for adverse reaction, 9 (7.1%) for long distance from the
      hospital, and 4 (3.1%) for having no time for treatment. And 69 (54.3%) of them
      stopped SCIT in the first year, 28 (22.1%) in the second year, and 30 (23.6%) in
      the third year. Currently, 85 cases (66.9%) of the 127 asthmatic children were up
      to the control level, and the other 42 cases were not. There was significant
      difference in the control level of asthma berween the group receiving treatment
      with regular inhaled corticosteroids (ICS) and the group receiving treatment with
      irregular ICS (P<0.01). CONCLUSIONS: Bad efficacy, remission of asthma, expensive
      fees, complex process of treatment, and adverse reaction are the main reasons
      contributing to the stop of SCIT in asthmatic children. To improve the compliance
      with SCIT, It is important to make the patients and their parents understand the
      long treatment course and slow effect of SCIT, encourage them to use objective
      indices for evaluating the state of asthma, and effectively prevent and treat the
      adverse reactions.

PMID- 22989437
TI  - [Investigation of current infection with Helicobacter pylori in children with
      gastrointestinal symptoms].
AB  - OBJECTIVE: To investigate current infection with Helicobacter pylori (H. pylori)
      and related risk factors in children with gastrointestinal symptoms. METHODS: A
      total of 376 children with upper gastrointestinal symptoms were examined by
      gastroscopy. Three pieces of gastric mucosa were sampled for rapid urease test
      and pathohistological examination. Some children received 13C-urea breath test.
      Children with two or more positive results were diagnosed with H. pylori
      infection. A questionnaire on living environment, family economic status,
      parents' education level and family history of gastrointestinal diseases was
      completed for all children. RESULTS: The H. pylori infection rate was 44.9%
      (169/376) in children with upper gastrointestinal symptoms. There was no
      statistical difference in the infection rate between males and females (P>0.05).
      The H. pylori infection rates in the 3 to 7-year old, 8 to 12-year old and 13 to
      16-year-old children were 39.5% (47/119), 41.0% (55/134), and 54.5% (67/123)
      respectively, with significant differences between different age groups
      (chi2=6.76, P<0.05). The H. pylori positive rate was significantly higher in
      children who were in full-time nursery or collective living and dining than in
      those who were not (53.6% vs 40.6%; P<0.05). The H. pylori positive rate in high
      income families was lower than that in middle to low-income families (36.9% vs
      48.3%; P<0.05). In addition, the H. pylori positive rate in children with well
      educated parents was lower than in those with parents who had not received higher
      education (39.5% vs 50.8%; P<0.05). The H. pylori infection rate in children with
      a family history of digestive disease was significantly higher than in those
      without family history of gastrointestinal diseases (52.9% vs 41.2%; P<0.05).
      CONCLUSIONS: The infection rate increases with age and is higher in children who
      are in collective living and dining, come from low income family, have parents
      who have not received higher education and have a family history of upper
      gastrointestinal diseases.

PMID- 22989438
TI  - [Clinical manifestations and gene mutations of a Chinese family with MYH9-related
      syndrome].
AB  - OBJECTIVE: To explore the method for early diagnosis and pathogenesis of MYH9
      related syndrome through analysis of the clinical manifestation and gene mutation
      of a Chinese family with MYH9-related syndrome. METHODS: Peripheral blood samples
      were collected from a three-generation Chinese family with MYH9-related syndrome
      (11 individuals, including 3 patients) and 100 healthy individuals. Polymerase
      chain reaction (PCR) amplification and direct sequencing of DNA were performed to
      analyze mutations of MYH9 gene. RESULTS: Thrombocytopenia, increased volume of
      platelet, and granulocyte inclusion bodies were found in the patients with MYH9
      related syndrome via a peripheral blood test. A missense mutation of a base pair
      (G-A) in exon 30 was revealed by PCR amplification and direct sequencing of MYH9
      of the proband. That lead to Asp-Asn substitution at position 1424 (D1424N
      mutation). The mutation was the same as in other patients with MYH9-related
      syndrome. It was not found in healthy people from the Chinese family or in the
      other 100 healthy individuals. CONCLUSIONS: Patients with MYH9-related syndrome
      show diverse symptoms. Mutation of MYH9 gene may be the molecular mechanism of
      MYH9-related syndrome, and D1424N mutation of MYH9 has not been reported in
      Chinese people. Early diagnosis of MYH9-related syndrome can be carried out by
      investigating family history and making early examinations.

PMID- 22989439
TI  - [Association of cytotoxic T lymphocyte-associated antigen-4+49A/G polymorphism
      with childhood type 1 diabetes mellitus: a meta-analysis].
AB  - OBJECTIVE: To evaluate the association of cytotoxic T lymphocyte-associated
      antigen-4 (CTLA-4) + 49A/G polymorphism with type 1 diabetes mellitus (T1DM) in
      children. METHODS: Papers about the association of CTLA4+49A/G polymorphism with
      T1DM in children were collected by searching PubMed, EBSCO, CBM, CNKI, and
      Wanfang Data. A meta-analysis was performed to examine differences in the
      genotypes (AG, GG, and GG+AG) and G allele at position 49 of the CTLA-4 gene
      between a childhood T1DM group and a control group. RESULTS: A total of 10 papers
      involving 1084 T1DM children and 1338 healthy children were included. The Meta
      analysis was performed to evaluate the association of the genotypes (AG, GG, and
      GG+AG) and the G allele at position 49 of the CTLA-4 gene with T1DM using a fixed
      effect model according to the heterogeneity test results of all studies. The
      pooled OR values (95% CI) were 1.13 (0.97-1.33), 1.42 (1.16-1.75), 1.20 (1.03
      1.40), and 1.21 (1.09-1.33), suggesting a significant difference in genotypes
      (AG, GG, and GG+AG) and the G allele at position 49 of the CTLA-4 gene between
      the two groups. CONCLUSIONS: CTLA-4 +49A/G polymorphism is associated with T1DM
      in children.

PMID- 22989440
TI  - [An epidemiological survey of attention deficit hyperactivity disorder in school
      age children in Shenzhen].
AB  - OBJECTIVE: To investigate the prevalence of attention deficit hyperactivity
      disorder (ADHD) and behavior problems among school-age children in Shenzhen City
      of Guangdong. METHODS: A total of 10553 students in Grades 1-6 from different
      primary schools in Shenzhen City were assessed by Conners Parent Symptom
      Questionnaire (PSQ) and Conners Teacher Rating Scale (TRS). Children showing
      abnormalities according to PSQ or TRS were further assessed according to the
      diagnostic standard for ADHD as laid out in the diagnostic and statistical manual
      for mental disorders- 4th edition (DSM-IV). RESULTS: A total of 8193 PSQ and TRS
      assessments were completed. The children were aged from 7 to 13 years. The total
      prevalence rate was 7.60% by PSQ and 5.59 % by TRS. Four hundred and forty-two
      children were diagnosed having ADHD by DSM-IV, with a prevalence rate of 5.39%.
      There were significant differences in the prevalence rate of ADHD among children
      aged 7 to 13 years (chi2=21.613, P<0.05). In children aged 7 to 9 years, the
      prevalence rate was higher (above 6%). The prevalence rate of ADHD in boys was
      significantly higher than in girls (6.65% vs 3.12%; P<0.05). Impulsion and
      hyperactivity (79.6%), learning (60.6%) and conduct disorders (52.0%) were the
      main behavioral problems in children with ADHD. The prevalence of learning
      disorders was higher in girls than in boys. Conclusions The prevalence rate of
      ADHD in children from primary schools in Shenzhen City is 5.39%, and it is higher
      in children aged 7 to 9 years. Boys have a higher prevalence rates of ADHD than
      girls. Impulsion and hyperactivity, learning and conduct disorders are common
      problems in children with ADHD.

PMID- 22989441
TI  - [A retrospective study on the progression of myopia in school-age children].
AB  - OBJECTIVE: To study the progression of myopia in school-age children over the
      past 12 years and factors influencing myopia progression. METHODS: A total of
      4569 cases of 5 to 12-year-old children who had refractive examinations in the
      Third Xiangya Hospital, Central South University between January 2000 and
      December 2011 were enrolled in this study. The children had no family history of
      congenital high myopia or other eye diseases. Myopia progression was evaluated
      when the children were re-examined. The refractive state of each child was
      measured with cyclopiegic retinoscopy. RESULTS: The mean spherical equivalent
      (SE) myopia was-2.0+/-1.7 D between January 2000 and December 2011. There was no
      statistical difference in yearly myopia progression between different years. The
      average age of the myopic children decreased from 10.1 in 2000 to 8.9 years old
      in 2011 (P<0.05). Mean myopia progression was -0.6+/-0.7 D per year from 2000 to
      2011. Myopia progression reduced gradually in 5 to 8-year-olds (P<0.05), however,
      it accelerated between ages 9 and 11 years. Myopia progression in 10- and 11-year
      olds was significantly greater than in 7- and 8-year-olds (P<0.01). The multiple
      linear regression analysis demonstrated that age and baseline myopic refraction
      were positively related to myopia progression. CONCLUSIONS: There was no obvious
      change in the yearly myopia progression of the children over the past 12 years.
      The mean age of myopia occurrence became younger with time. More preventive
      measures are needed to ward off high myopia in children with moderate myopia,
      especially those aged over 10 years.

PMID- 22989442
TI  - [Changes of neuroglobin in the pathologic process of contusion and laceration of
      brain in children].
AB  - OBJECTIVE: To study the role of neuroglobin (Ngb) in the pathologic process of
      contusion and laceration of brain in children. METHODS: The proteins in the brain
      tissue were extracted by two-dimensional gel electrophoresis in 3 children
      undergoing brain ventricular neoplasms resection (normal brain tissue) and in 8
      children with contusion and laceration of brain. The image analysis was done
      using the PDQuest 7.0 software. The differential protein spots were detected and
      analyzed with Applied Biosystems Voyager System 4307 MALDI-TOF Mass Spectrometer
      and bioinformatical skills. Ngb expression in the brain tissue was measured using
      immunohistochemisty. Ngb expression in plasma was measured using ELISA in 15
      children with contusion and laceration of brain and 10 healthy children. RESULTS:
      Expression maps of the brain tissue were established by two-dimensional gel
      electrophoresis in children with contusion and laceration of brain and healthy
      children. Six differential protein spots were found and 5 of them were identified
      by mass spectrum. Immunohistochemisty assay showed that Ngb expression in the
      brain tissue in children with contusion and laceration of brain was significantly
      higher than in normal controls (P<0.05). ELISA results showed that Ngb expression
      in the plasma increased significantly 6, 12, 18, 24 and 48 hours after trauma in
      children with contusion and laceration of brain compared with healthy children
      (P<0.01). CONCLUSIONS: Ngb may play an important role in the pathologic process
      of contusion and laceration of brain in children.

PMID- 22989443
TI  - [Effects of early environment on the expression of brain-derived neurotrophic
      factor and its receptor and brain development].
AB  - OBJECTIVE: To study the effect of early environment on the learning-memory
      ability of rats and the expression of brain-derived neurotrophic factor (BDNF)
      and its receptor, tyrosine kinase receptor B (TrkB), and to explore the influence
      of early environment on development of rat brain in developing stage and possible
      regulation mechanisms. METHODS: Forty-five newborn Sprague-Dawley rats were
      randomly divided into three groups (15 rats in each group): enriched environment
      group (EE group), isolated environment group (IE group) and normal control group
      (NC group). The pups were nurtured separately in their groups. The learning
      memory abilities of the rats were measured by "Y"-arm maze test 28 to 29 days
      after birth. The number of neural cells and the expression of BDNF and TrkB in
      the hippocampal CA3 and frontal lobe were were detected by Nissl's staining and
      immunohistochemistry respectively. RESULTS: The results of the "Y"-arm maze test
      showed that rats in the EE group needed less training times, and retained a
      higher percentage of memory than the other two groups(P<0.01). Rats in the IE
      group needed more training times, and retained a lower percentage of memory than
      the NC group (P<0.01). By Nissl's staining, the numbers of neural cells in the
      hippocampal CA3 and frontal lobe were highest in the EE group followed by the NC
      group. They were lowest in the IE group (P<0.01). By immunohistochemistry, the
      expression of BDNF in the hippocampal CA3 and frontal lobe were highest in the EE
      group followed by the NC group. It was lowest in the IE group (P<0.01). Results
      were similar for expression of TrkB. CONCLUSIONS: Early environment can affect
      the long-term brain development and brain function of rats by influencing the
      expression of BDNF and its receptor TrkB in the hippocampus and frontal lobe.

PMID- 22989444
TI  - [Role of miRNA-126/miRNA-126* in the fetal lung development of rats].
AB  - OBJECTIVE: To investigate the expression and role of miRNA-126/miRNA-126(*) in
      the fetal lung development of rats. METHODS: Twelve pregnant Sprague-Dawley rats
      were randomly divided into 3 groups and the fetal rats were removed at 16, 19 and
      21 days of gestation respectively. Hematoxylin and eosin staining was performed
      to observe lung morphology of fetal rats. Then microRNA (miRNA) microarray was
      used to study the expression patterns of miRNA-126/miRNA-126(*) in fetal lungs at
      the three time points. And miRNA-126(*) was selected for further study by real
      time PCR. RESULTS: There was no evident difference in the expression of miRNA-126
      among the three groups, however the expression level of miRNA-126(*) increased
      gradually as the fetal lung developed. The real-time PCR result further showed
      that expression of miRNA-126(*) increased gradually with lung development,
      displaying significant differences among the three groups (P<0.05). CONCLUSIONS:
      miRNA-126(*) may play an important role in development of the fetal lung in rats.

PMID- 22989445
TI  - [Upper gastrointestinal bleeding and hyperglycemia induced by acute alcoholism in
      an infant].

PMID- 22989446
TI  - [Pyogenic osteomyelitis of femoral bone in a neonate].

PMID- 22989447
TI  - [Trichothiodystrophy complicated by SIBI(D)S syndrome: a case report].

PMID- 22989448
TI  - [A new component of breast milk: microRNA].
AB  - MicroRNA (miRNA) is a class of non-coding endogenous small molecule single strand
      RNA which is found in human body fluids. In recent years, miRNAs have been found
      in breast milk and parts of miRNAs are related to immune organ development and
      regulation of the immune function in infants. This article summarizes the
      functions of miRNA in breast milk and evidence-based clinical practice, and the
      differences between microRNA content and species in breast milk and cow milk.
      Understanding the role of miRNA can bring new opportunities for childhood
      nutrition research.

PMID- 22989450
TI  - Role of the French rescue teams in Diquini Hospital: Port-au-Prince, January
      2010.
AB  - On January 12, 2010, Port-au-Prince, Haiti, was shattered by a violent earthquake
      that killed or injured thousands of its citizens. Local emergency services became
      overwhelmed and international assistance was required. French relief teams were
      deployed to assist local hospitals in caring for the victims. The medical care
      activity of the team at Diquini Hospital from January 17-26 was analyzed.
      Priority was given to surgery, leading to the creation of a pre- and post
      operative area and a medical care unit. Special attention was required for
      infection prevention, pain relief, minor surgery, and pre-surgery triage. The
      continual influx of accompanied victims necessitated the creation of a receiving
      area. In spite of the assistance from several foreign surgical teams, some
      patients had to be evacuated to French or American facilities, particularly
      children, patients with spinal cord injuries, and those needing intensive care.
      Analysis of the actions undertaken highlights the importance of well-prepared and
      flexible medical teams and the ability to provide local and regional anesthesia,
      including the necessary medical supplies and equipment. Medical care activity,
      especially post-surgical care, was a predominant, ongoing need. The ability to
      provide medical care required organization and cooperation among local health
      care providers and other relief workers.

PMID- 22989449
TI  - Identifying the seasonal origins of human campylobacteriosis.
AB  - Human campylobacteriosis exhibits a distinctive seasonality in temperate regions.
      This paper aims to identify the origins of this seasonality. Clinical isolates
      [typed by multi-locus sequence typing (MLST)] and epidemiological data were
      collected from Scotland. Young rural children were found to have an increased
      burden of disease in the late spring due to strains of non-chicken origin (e.g.
      ruminant and wild bird strains from environmental sources). In contrast the adult
      population had an extended summer peak associated with chicken strains. Travel
      abroad and UK mainland travel were associated with up to 17% and 18% of cases,
      respectively. International strains were associated with chicken, had a higher
      diversity than indigenous strains and a different spectrum of MLST types
      representative of these countries. Integrating empirical epidemiology and
      molecular subtyping can successfully elucidate the seasonal components of human
      campylobacteriosis. The findings will enable public health officials to focus
      strategies to reduce the disease burden.

PMID- 22989451
TI  - A fluorescent-based high-throughput screening assay for small molecules that
      inhibit the interaction of MdmX with p53.
AB  - A fluorescent-based high-throughput screening (HTS) assay for small molecules
      that inhibit the interaction of MdmX with p53 was developed and applied to
      identify new inhibitors. The assay evaluated the MdmX-p53 interaction by
      detecting the quenching of the fluorescence of green fluorescent protein (GFP)
      fused to the MdmX protein, after its interaction with a p53 peptide labeled with
      a fluorescence quencher. In this report, the developed HTS assay was applied to
      about 40 000 compounds, and 255 hit compounds that abrogated the GFP quenching
      were selected. Next, the obtained hits were reevaluated by other assays. First,
      their effects on the diffusion time of a fluorescently-labeled p53 peptide after
      incubation with the MdmX protein were tested by measuring the diffusion time
      using fluorescence correlation spectroscopy, and six stable hit compounds with
      IC(50) values less than 5 uM were selected. Next, we further confirmed their
      inhibition of the MdmX-p53 interaction by surface plasmon resonance. To indicate
      the efficacy of the hit compound as a candidate anticancer drug, we showed that
      the hit compound triggered apoptosis after p53 and p21 accumulation in cultured
      MV4;11 leukemia cells. Thus, the new HTS assay is effective for obtaining novel
      MdmX-p53 interaction inhibitors that are valuable as candidate compounds for
      cancer treatment.

PMID- 22989452
TI  - [Effect of Src tyrosine kinase inhibition on the drug-resistance as well as MDR1
      and LRP expression of the human cis-platinum-resistant lung cancer cell line
      A549/DDP].
AB  - BACKGROUND: The aim of this study is to investigate the effect of Src tyrosine
      kinase inhibition on the drug-resistance as well as the expression of multidrug
      resistance 1 (MDR1) and lung resistance-related protein (LRP) of the human cis
      platinum-resistant lung cancer cell line A549/DDP. METHODS: 4-Anilinoquirazoline
      was used to inhibit Src tyrosine kinase activity in A549/DDP. Western blot
      analysis was used to detect the Src tyrosine kinase activity. CellTiter-Glo assay
      was used to detect the drug sensitivity of tumor cells. Flow cytometry was used
      to detect the intracellular Rh-123 content. Western blot and real-time PCR assay
      were used to detect the expression of tumor MDR1 and LRP. RESULTS: 4
      Anilinoquirazoline can down-regulate the cellular Src tyrosine kinase activity in
      A549/DDP. After treatment with 2.5 MUM and 10 MUM of 4-anilinoquirazoline, the
      cells became more sensitive to the drug and the reversal folds (RFs) of tumor
      cell sensitivity to the drug were 1.59- and 2.10-fold, respectively. The
      intracellular content of Rh-123 improved by 1.21- and 1.59-fold, respectively.
      The mRNA levels of MDR1 were 53.8% and 27.5% of the control, respectively. The
      mRNA level of LRP was 59.3% and 21.4% of the control, respectively. The
      expression of MDR1 and LRP protein significantly decreased. CONCLUSIONS: The
      inhibition of Src tyrosine kinase activity in A549/DDP cells can reverse multi
      drug resistance and increase the sensitivity of the cells to the drug. The
      mechanism may be related to the down-regulation of cellular MDR1 and LRP.

PMID- 22989453
TI  - [Gemcitabine combined with vinorelbine in the treatment of refractory patients
      with advanced non-small cell lung cancer: a multi-center retrospective study].
AB  - BACKGROUND: The aim of this study is to detect the efficacy and toxicity of
      gemcitabine and vinorelbine (GN as second-line or further-line treatment) in
      refractory advanced non-small cell lung cancer (NSCLC) patients in China.
      METHODS: We retrospectively reviewed 53 NSCLC patients treated with this agent at
      four hospital in China from Jan 01, 2004 to Jun 30, 2010. Survival analysis was
      evaluated by Kaplan-Meier method. RESULTS: A total of 53 patients were analyzed
      in this study (28 patients in second-line and 25 in third- or further-line
      treatment). The objective response rate (ORR) was 9.4%. The disease control rate
      (DCR) was 56.6%. The progression-free survival (PFS) and median overall survival
      (OS) was 3.0 and 17.6 months, respectively. Univariate analysis, revealed
      performance status (PS) score was an independent prognostic factor for overall
      survival. CONCLUSIONS: The GN agent is effective for the second-line or further
      line treatment in advanced non-small cell lung cancer. The toxicity is well
      tolerated .

PMID- 22989454
TI  - [EGFR gene mutation statuses in advanced non-small cell lung cancer patients and
      their influence on effect of gefitinib].
AB  - BACKGROUND: It has been proven that the status of epidermal growth factor
      receptor (EGFR) gene mutation was related to effects of gefitinib in patients
      with advanced non-small cell lung cancer (NSCLC). The aim of this study is to
      reports distribution of EGFR gene mutations in advanced NSCLC and their influence
      on effect of gefitinib. METHODS: From Jan 2007 to Dec 2009, 160 patients with
      advanced non-squamous NSCLC received EGFR mutation tests, and EGFR exon 19 and 21
      were amplified by mutant-enriched PCR and analyzed by sequencing. Among those
      patients, 111 received gefitinib therapy. Overall survival (OS) and progression
      free survival (PFS) were calculated using the Kaplan-Meier method and a Cox
      regression analysis was used to detect differences between strata. RESULTS: The
      percentage of EGFR mutation in advanced non-squamous NSCLC was 55%, and it was
      only significantly related with pathological type. OS of the patients with or
      without EGFR gene mutations were 29.0 months (95%CI: 24.2-33.8) and 21.0 months
      (95% CI: 14.7-27.3) respectively, and the difference was not significant. PFS of
      patients with or without EGFR gene mutations were 17.0 months (95% CI: 5.6-17.6)
      and 11.6 months (95% CI 8.6-25.4), and the difference was significant (P =
      0.022). Multivariate analysis shows that OS was significantly related with ECOG
      status, pathological type and EGFR mutation statuses, and PFS was significantly
      related to ECOG status, former regimens number and EGFR mutation statuses. There
      were no significant differences in OS and PFS between patients with EGFR exon 19
      deletions and those with exon 21 point mutation. CONCLUSIONS: PFS of patients
      with EGFR mutations was better than those without EGFR mutations, but OS was
      similar. There were no significant differences in OS and PFS between patients
      with EGFR exon 19 deletions and those with exon 21 point mutation.

PMID- 22989455
TI  - [Expression and bioinformatic analysis of ornithine aminotransferase ?in non
      small cell lung cancer].
AB  - BACKGROUND: It has been proven that ornithine aminotransferase (OAT) might play
      an important role in the oncogenesis and progression of numerous malignant
      tumors. The aim of this study is to detect the mRNA and protein expression of OAT
      in non-small cell lung cancer (NSCLC), as well as to analyze the bioinformatic
      features and binary interactions. METHODS: OAT mRNA expression was detected in
      A549 and 16HBE cell lines by reverse transcription-polymerase chain reaction. OAT
      protein expression was determined in 55 cases of NSCLC and 17 cases of adjacent
      non-tumor lung tissues by immunohistochemical staining. The bioinformatic
      features and binary interactions of OAT were analyzed. Gene ontology annotation
      and signal pathway analysis were performed. RESULTS: OAT mRNA expression in A549
      cells was 2.85-fold lower than that in 16HBE cells. OAT protein expression was
      significantly higher in NSCLC tissues than that in adjacent non-tumor lung
      tissues. A significant difference of OAT protein expression was existed between
      squamous cell lung cancer and adenocarcinoma (P < 0.05), but was not correlated
      with the gender, age, lymph node metastasis, tumor size, and TNM stages.
      Bioinformatic analysis suggested that OAT was a highly homologous and stable
      protein located in the mitochondria. An aminotran-3 domain and several sites of
      phosphorylation, which may function in signal transduction, gene transcription,
      and molecular transit, were found. In the 54 selected binary interactions of OAT,
      TNF and TRAF6 play roles in the NF-kappaB pathway. CONCLUSIONS: OAT may play an
      important role in the oncogenesis and progression of NSCLC. Thus, OAT may be a
      novel biomarker for the diagnosis of NSCLC or a new target for its treatment.

PMID- 22989456
TI  - [Retrospective study on lobe-specific lymph node dissection for patients with
      early-stage non-small cell lung cancer].
AB  - BACKGROUND: The aim of this study is to explore the effects of different modes of
      lymph node dissection in early-stage non-small cell lung cancer (NSCLC) on the
      survival rate, to study the prognostic factors, and to discuss the clinical
      application of lobe-specific lymph node dissection. METHODS: A total of 379
      patients with completely resected pathological stage I NSCLC between the years
      1998 and 2005 at Shanghai Chest Hospital were retrospectively analyzed. Among the
      patients, 148 were placed in the systematic lymph node dissection group and 150
      in the lobe-specific lymph node dissection group. All of them were in
      pathological stage I (T1a-2aN0M0). The differences between the two groups were
      compared. RESULTS: No statistical difference was found between the two sets of
      data in terms of the clinical and pathological features of distribution (P >
      0.05). The overall survival distribution between the two groups had no
      statistical difference (P > 0.05). The pathological stage, pathological type, and
      tumor size significantly differed between the two groups. The duration of
      surgery, blood loss, blood transfusion, drain secretion, duration of drainage,
      and duration of hospital stay also significantly differed between the two groups
      (P < 0.01). The complications significantly differed between the two groups as
      well (P < 0.05). CONCLUSIONS: Systematic lymph node dissection does not improve
      the five-year survival rates in pathological stage I NSCLC. The pathological
      stage, pathological type, and tumor size critically affect the prognosis. Lobe
      specific lymph node dissection can significantly reduce complications and
      perioperative risks.

PMID- 22989457
TI  - [Effect of amifostine on locally advanced non-small cell lung cancer patients
      treated with radiotherapy: a meta-analysis of randomized controlled trials].
AB  - BACKGROUND: Controversy exists on whether amifostine can reduce the efficacy and
      decrease the side effects of non-small cell lung cancer (NSCLC) treated by
      radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side
      effects of amifostine in NSCLC patients treated with radiotherapy. METHODS: Open
      published randomized controlled trials on the efficacy and side effects of
      amifostine in NSCLC patients treated with radiotherapy were collected from
      Medline, Cochrane Central Register of Controlled Trials, EMBSE, CBM, CNKI,
      WANFANG, American Society of Clinical Oncology, and European Society of Medical
      Oncology databases. The pooled efficacy and side effects of amifostine in these
      patients were calculated using the statistics software Stata 11.0. RESULTS: Nine
      trials that included 769 (381 and 388 in each arm) patients were analyzed. The
      pooled relative risk of complete, partial, and objective responses were 1.16 (95%
      CI: 0.90-1.50, Z = 1.07, P = 0.29), 1.02 (95% CI: 0.87-1.19, Z = 0.21, P = 0.83)
      and 1.06 (95% CI: 0.97-1.17, Z = 1.31, P = 0.20), respectively. The side effects
      in seven trials including 738 (367 and 371 in each arm) patients were analyzed.
      The pooled relative risk of developing grades 3 to 4 esophagitis and pneumonitis
      were 0.51 (95% CI: 0.37-0.72, Z = 3.88, P < 0.001) and 0.51 (95% CI: 0.26-0.99, Z
      = 1.98, P = 0.04), respectively. CONCLUSIONS: Amifostine can significantly
      decrease the risk of developing serious esophagitis and pneumonitis without
      reducing the response rate in NSCLC patients treated by radiotherapy.

PMID- 22989458
TI  - [Advances of molecular subtype and targeted therapy of lung cancer].
AB  - The discovery of multiple molecular mechanisms underlying the development,
      progression, and prognosis of lung cancer, has created new opportunities for
      targeted therapy. Each subtype is associated with molecular tests that define the
      subtype and drugs that may have potential therapeutic effect on lung cancer. In
      2004, mutations in the epidermal growth factor receptor (epidermal growth factor
      receptor, EGFR) gene were discovered in non-small cell lung cancers (NSCLC),
      especially in adenocarcinomas. And they are strongly associated with sensitivity
      to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Moreover, in 2007 the existence
      of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma
      kinase (EML4-ALK) fusion gene was discovered in NSCLC, and the same as EGFR-TKIs,
      ALK inhibitors are being found to be highly effective in lung cancers. At
      present, multiple molecular subtype of lung cancer and relevant targeted drugs
      are undering study. Here, we review the remarkable progress in molecular subtype
      of lung cancer and the related targeted therapy.

PMID- 22989459
TI  - [Advance of prophylactic cranial irradiation in lung cancer].

PMID- 22989460
TI  - [Pulmonary giant spherical mass--one case of intracranial hemangiopericytoma
      metastatic to lungs].

PMID- 22989461
TI  - Impact of breast cancer subtypes and treatment on survival: an analysis spanning
      two decades.
AB  - BACKGROUND: We investigated the impact of breast cancer molecular subtypes and
      treatment on survival in a cohort of medically insured women followed for more
      than 20 years. METHODS: We examined 934 female members of an integrated health
      care delivery system newly diagnosed with invasive breast cancer between 1988 and
      1995 and followed them through 2008. Tumors were classified into four molecular
      subtypes on the basis of their expression profile: luminal A; luminal B; basal
      like; and HER2-enriched. We followed women from the surgery date to death, health
      plan disenrollment, or study's end. HR and 95% confidence intervals (CI) were fit
      using Cox proportional hazards models adjusting for cancer treatments and tumor
      characteristics. RESULTS: A total of 223 (23.9%) women died because of breast
      cancer during the 21-year study period. Compared with women with luminal A
      tumors, women with HER2-enriched (HR 2.56, 95% CI 1.53-4.29) and luminal B tumors
      (HR 1.96, 95% CI: 1.08-3.54) had roughly a two-fold increased adjusted risk of
      breast cancer mortality. In addition, the survival curves suggest that risk of
      late mortality persists in women with luminal A tumors. CONCLUSION: Among women
      with health care coverage, molecular subtypes were important predictors of breast
      cancer mortality. Women with HER2-enriched tumors and luminal B subtypes had the
      poorest survival despite adjusting for important covariates. IMPACT: In a cohort
      followed for more than 20 years, women with HER2-enriched tumors had worse
      survival, but interestingly, the survival curve for women with luminal A tumors
      continued to steadily decline after 10 years of follow-up.

PMID- 22989462
TI  - Viability of primary term cytotrophoblast cell culture in normoxia and hypoxia.
AB  - Cytotrophoblast (CT) cells isolated and purified from term placenta are able to
      differentiate into syncytiotrophoblast cells. Previous reports suggested that
      hypoxia is an inhibitor of this differentiation and also increases apoptosis. As
      visual observations of our CT cell cultures indicated a better development in
      hypoxia than in normoxia (defined as 2.5 and 21% O(2), respectively), we decided
      to assess the effect of low oxygen tension on in vitro CT cell differentiation by
      measuring cell viability, apoptosis and CT cell fusion and differentiation. We
      observed a 45% decrease in cell viability 24 h after plating both in normoxia and
      in hypoxia but no difference between the two oxygen conditions. Cell viability
      remained stable during the 4-day culture. Apoptosis also did not increase in
      hypoxia. Apoptotic index and caspase activation were even lower in hypoxia than
      in normoxia at Day 1 and Day 4 of the culture. Finally, we observed a 5-fold and
      6-fold increase in Syncytin-1 mRNA expression in normoxia and in hypoxia,
      respectively, indicating that hypoxia did not inhibit CT cell fusion. CT cells
      differentiated as well in hypoxia as an increase in inhibin alpha subunit mRNA
      was evidenced during the 4-day culture. This increase was even higher in hypoxia
      than in normoxia. In conclusion, hypoxia defined as 2.5% O(2) based on first
      trimester placental pO(2) did not decrease term primary CT cell viability and did
      not increase apoptosis. Moreover, it did not inhibit either CT cell fusion or
      differentiation.

PMID- 22989463
TI  - Identifying abnormalities in symbiotic development between Trifolium spp. and
      Rhizobium leguminosarum bv. trifolii leading to sub-optimal and ineffective
      nodule phenotypes.
AB  - BACKGROUND AND AIMS: Legumes overcome nitrogen limitations by entering into a
      mutualistic symbiosis with N(2)-fixing bacteria (rhizobia). Fully compatible
      associations (effective) between Trifolium spp. and Rhizobium leguminosarum bv.
      trifolii result from successful recognition of symbiotic partners in the
      rhizosphere, root hair infection and the formation of nodules where N(2)-fixing
      bacteroids reside. Poorly compatible associations can result in root nodule
      formation with minimal (sub-optimal) or no (ineffective) N(2)-fixation. Despite
      the abundance and persistence of strains in agricultural soils which are poorly
      compatible with the commercially grown clover species, little is known of how and
      why they fail symbiotically. The aims of this research were to determine the
      morphological aberrations occurring in sub-optimal and ineffective clover nodules
      and to determine whether reduced bacteroid numbers or reduced N(2)-fixing
      activity is the main cause for the Sub-optimal phenotype. METHODS: Symbiotic
      effectiveness of four Trifolium hosts with each of four R. leguminosarum bv.
      trifolii strains was assessed by analysis of plant yields and nitrogen content;
      nodule yields, abundance, morphology and internal structure; and bacteroid
      cytology, quantity and activity. KEY RESULTS: Effective nodules (Nodule Function
      83-100 %) contained four developmental zones and N(2)-fixing bacteroids. In
      contrast, Sub-optimal nodules of the same age (Nodule Function 24-57 %) carried
      prematurely senescing bacteroids and a small bacteroid pool resulting in reduced
      shoot N. Ineffective-differentiated nodules carried bacteroids aborted at stage 2
      or 3 in differentiation. In contrast, bacteroids were not observed in Ineffective
      vegetative nodules despite the presence of bacteria within infection threads.
      CONCLUSIONS: Three major responses to N(2)-fixation incompatibility between
      Trifolium spp. and R. l. trifolii strains were found: failed bacterial
      endocytosis from infection threads into plant cortical cells, bacteroid
      differentiation aborted prematurely, and a reduced pool of functional bacteroids
      which underwent premature senescence. We discuss possible underlying genetic
      causes of these developmental abnormalities and consider impacts on N(2)-fixation
      of clovers.

PMID- 22989464
TI  - Identification of two paralogous caprine CD36 genes that display highly divergent
      mRNA expression profiles.
AB  - The CD36 molecule plays a pivotal role in a variety of immunological and cellular
      processes, including pathogen recognition, inflammation and apoptosis. Herein, we
      demonstrate that this gene is duplicated in goats, with two copies (CD36 and CD36
      like) that display highly divergent mRNA expression profiles. In this way, CD36
      mRNA is mostly expressed in the adipose tissue and heart whilst CD36-like mRNA
      shows a high expression in the liver. We have also found evidence of the presence
      of two paralogous CD36 and CD36-like genes in the bovine genome, suggesting that
      CD36 duplication took place before goat-cattle radiation, i.e. at least 20 MYR
      ago. Finally, we have characterized the polymorphism of the coding regions of the
      goat CD36 and CD36-like genes. In doing so, we have identified one synonymous
      polymorphism at the CD36-like gene (c.390A>C) that displays a significant
      association (P=0.04) with milk somatic cell count, a parameter often used to
      diagnose mastitis in domestic ruminants.

PMID- 22989465
TI  - Deciphering puberty: novel partners, novel mechanisms.
AB  - Puberty is a fascinating developmental phase that involves the attainment of
      reproductive capacity and the completion of sexual and somatic maturation. As a
      life-changing event, puberty onset is precisely controlled by interconnected
      regulatory pathways that are sensitive to numerous endogenous signals and
      environmental cues. The mechanisms of normal puberty and its potential deviations
      have been thoroughly studied in humans and model species. Yet, characterization
      of the neurobiological basis of puberty is still incomplete. Progress on this
      front is not only relevant from a physiological perspective but would also help
      to unravel the underlying causes for the observed changes in the timing of
      puberty in humans, with a trend for earlier puberty onset, especially in girls.
      In this review, we will provide a synoptic overview of some recent developments
      in the field that have deepened our understanding of the neuroendocrine and
      molecular basis for the control of puberty onset. These include not only the
      demonstration of the involvement of the hypothalamic Kiss1 system in the control
      of puberty and its modulation by metabolic cues but also the identification of
      the roles of other neuropeptide pathways and molecular mediators in the
      regulation of puberty. In addition, the potential contribution of novel
      regulatory mechanisms, such as epigenetics, in the central control of puberty
      will be briefly discussed. Characterization of these novel players and regulatory
      mechanisms will improve our understanding of the basis of normal puberty and its
      eventual alterations in various pathological conditions.

PMID- 22989466
TI  - Endocrine disorders in childhood and adolescence. Natural history of subclinical
      hypothyroidism in children and adolescents and potential effects of replacement
      therapy: a review.
AB  - OBJECTIVE: Subclinical hypothyroidism (SH) is quite common in children and
      adolescents. The natural history of this condition and the potential effects of
      replacement therapy need to be known to properly manage SH. The aim of this
      review is to analyze: i) the spontaneous evolution of SH, in terms of the rate of
      reversion to euthyroidism, the persistence of SH, or the progression to over
      hypothyroidism; and ii) the effects of replacement therapy, with respect to
      auxological data, thyroid volume, and neuropsychological functions. METHODS: We
      systematically searched PubMed, Cochrane, and EMBASE (1990-2012) and identified
      39 potentially relevant articles of which only 15 articles were suitable to be
      included. RESULTS AND CONCLUSIONS: SH in children is a remitting process with a
      low risk of evolution toward overt hypothyroidism. Most of the subjects reverted
      to euthyroidism or remained SH, with a rate of evolution toward overt
      hypothyroidism ranging between 0 and 28.8%, being 50% in only one study (nine
      articles). The initial presence of goiter and elevated thyroglobulin antibodies,
      the presence of celiac disease, and a progressive increase in thyroperoxidase
      antibodies and TSH value predict a progression toward overt hypothyroidism.
      Replacement therapy is not justified in children with SH but with TSH 5-10 mIU/l,
      no goiter, and negative antithyroid antibodies. An increased growth velocity was
      observed in children treated with levothyroxine (l-T(4); two articles). l-T(4)
      reduced thyroid volume in 25-100% of children with SH and autoimmune thyroiditis
      (two studies). No effects on neuropsychological functions (one study) and
      posttreatment evolution of SH (one study) were reported.

PMID- 22989467
TI  - Serum cytokeratin 19 fragments: a dedifferentiation marker in advanced thyroid
      cancer.
AB  - BACKGROUND: This study was undertaken to evaluate serum cytokeratin 19 fragment
      (Cyfra 21.1) expressions in patients with advanced thyroid carcinoma and to
      explore the relationship between serum Cyfra 21.1 and the degree of radioiodine
      ((131)I) avidity of thyroid carcinoma cells. METHODS: Enrolled were 76
      consecutive patients with advanced thyroid carcinoma submitted to high-activity
      (131)I treatment. In each patient, serum thyroglobulin (Tg) and Cyfra 21.1 were
      measured before (131)I administration and compared with the posttreatment whole
      body scan results. RESULTS: Thirty-one (41%) of 76 patients had iodine-avid and
      45 (59%) had iodine-refractory diseases respectively. Significantly higher serum
      Cyfra 21.1, but not Tg, levels were found in patients with (131)I-refractory
      disease compared with patients with iodine-avid disease (P<0.01). CONCLUSIONS:
      This is the first report describing the potential role of serum Cyfra 21.1 as
      marker of dedifferentiation and resistance to (131)I therapy in patients with
      advanced thyroid carcinoma.

PMID- 22989468
TI  - Medullary thyroid carcinoma: the influence of policy changing in clinical
      characteristics and disease progression.
AB  - OBJECTIVE: Medullary thyroid carcinoma (MTC) has varying clinical course. We
      assessed trends in MTC presentation during the last 34 years. DESIGN:
      Retrospective study. METHODS: One hundred and fifty one patients (44.4% males)
      were followed for 0.934 years. Patients were classified according to year of
      diagnosis: group 1, 1977-2000 (n=53) and group 2, 2001-2011 (n=98). Extent of
      disease at diagnosis, during follow-up, number of surgeries, and pre- and
      postoperative calcitonin levels were recorded. RESULTS: In total, 48.34% reported
      family history of MTC. Group 1 had larger tumors (median 1.70 (intraquartile
      range (IQR) 1.7) vs 1.1 (1.2) cm, P=0.045, Mann-Whitney), they presented less
      frequently micro-MTCs (27.8 vs 46.1%, P=0.045), and underwent more multiple
      surgeries (63.3 vs 20.0%, P<0.001). Group 1 had more frequently progressive
      disease (35.8 vs 12.2%, P=0.003) and distant metastasis at follow-up (39.7 vs
      17.4%, P=0.017). Chronological group (HR 0.15, 95% CI 0.03-0.68, P=0.015) and
      distant metastases at follow-up (HR 0.07, 95% CI 0.015-0.30, P=0.001) were
      independently associated with 10-year disease progression (P<0.001). In sporadic
      cases, cervical lymph node invasion and distant metastases at diagnosis were more
      frequent in group 1 (72.7 vs 45.5%, P=0.032 and 27.3 vs 5%, P=0.019
      respectively); disease stage at diagnosis was more advanced (P=0.004). They
      underwent more multiple surgeries (P<0.001), presented more frequently distant
      metastasis at follow-up (67.7 vs 20.0%, P=0.002), had less frequently remission,
      and more frequently progressive disease (21.4 vs 58.0% and 64.3 vs 14.0%
      respectively, P<0.001). Postoperative calcitonin levels were higher (P=0.024).
      CONCLUSIONS: Recently, an increase in micro-MTCs is observed, while indices of
      invasiveness and persistence of disease are better. Increased awareness in
      familial cases, routine calcitonin measurements, and improved surgical procedures
      could be responsible.

PMID- 22989469
TI  - Fatigue and fatigue-related symptoms in patients treated for different causes of
      hypothyroidism.
AB  - OBJECTIVE: Research on determinants of well-being in patients on thyroid hormone
      replacement therapy is warranted, as persistent fatigue-related complaints are
      common in this population. In this study, we evaluated the impact of different
      states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore,
      the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu
      polymorphism, a common genetic variant of the TSHR, was analyzed. DESIGN: A cross
      sectional study was performed in 278 patients (140 patients treated for
      differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism
      (AIH)) genotyped for the TSHR-Asp727Glu polymorphism. METHODS: The
      multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with
      higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores
      were related to disease status and Asp727Glu polymorphism status. RESULTS: AIH
      patients scored significantly higher than DTC patients on all five MFI-20
      subscales (P<0.001), independent of clinical and thyroid hormone parameters. The
      frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more
      favorable MFI-20 scores than wild-type DTC patients on four of five subscales.
      The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC
      patients only. CONCLUSIONS: AIH patients had significantly higher levels of
      fatigue compared with DTC patients, which could not be attributed to clinical or
      thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism
      on fatigue in DTC patients should be confirmed in other cohorts.

PMID- 22989470
TI  - Submucosal tunnelling endoscopic resection for the treatment of esophageal
      submucosal tumours originating from the muscularis propria layer: an analysis of
      15 cases.
AB  - BACKGROUND AND AIMS: The aim of this prospective study was to evaluate the
      feasibility of submucosal tunnelling endoscopic resection of esophageal tumours
      originating from the muscularis propria layer. METHODS: Fifteen patients with
      esophageal submucosal tumours originating from the muscularis propria layer
      underwent submucosal tunnelling endoscopic resection between August 2011 and
      February 2012. The key steps were: (1) creating a submucosal tunnel from 5 cm
      above the tumour between the submucosal and muscular layers with a hook knife or
      hybrid knife; (2) dissecting the tumour by the technique of endoscopic submucosal
      dissection; (3) closing the mucosal incision site with clips after the tumour was
      removed. RESULTS: Submucosal tunnelling endoscopic resection was successfully
      performed in all cases. The en bloc resection rate was 100%. The average tumour
      diameter was 1.8 cm (range 1.0-3.0 cm). During the procedure, perforation
      occurred in 3 patients, who recovered after conservative treatment. No residual
      tumour or tumour recurrence was detected during the follow-up period (mean: 3.5
      months, range: 1-9 months). Pathological diagnoses of these tumours were
      leiomyomas (12/15) and gastrointestinal stromal tumours (3/15). CONCLUSIONS:
      Submucosal tunnelling endoscopic resection is a feasible method for the treatment
      of small esophageal submucosal tumours originating from the muscularis propria
      layer.

PMID- 22989471
TI  - Essential role of nitric oxide in acute ischemic preconditioning: S
      nitros(yl)ation versus sGC/cGMP/PKG signaling?
AB  - Nitric oxide (NO) plays an important role in acute ischemic preconditioning
      (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine
      monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated
      protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role
      in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous
      studies, we have shown that IPC-induced cardioprotection could be blocked by
      treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO
      synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify
      NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved
      in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the
      dark to prevent SNO decomposition by light exposure. Treatment with 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of
      sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC
      induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does
      not play an important role in NO-mediated cardioprotective signaling during acute
      IPC. In addition, treatment with ODQ in IPC hearts provided an additional
      protective effect on functional recovery, in parallel with a higher SNO level in
      these ODQ+IPC hearts. In conclusion, these results suggest that the protective
      effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling
      pathway, but rather through SNO signaling in IPC-induced acute cardioprotection.

PMID- 22989473
TI  - Lateralization of motor control in the human nervous system: genetics of mirror
      movements.
AB  - Mirror movements (MM) are a peculiar motor defect in humans where the intended
      unilateral movement of a body part results in involuntary movement of the same
      body part on the opposite side. This loss in the lateralization of motor control
      can be caused by genetic mutations that result in an aberrant projection of the
      corticospinal tract. However, recent evidence suggests that the same genes
      controlling corticospinal tract development also play roles in the development of
      other circuits involved in motor control, including local spinal circuits and the
      corpus callosum. These recent studies in humans and mouse models of MM will be
      discussed to provide an overview of the basis of MM and the molecular mechanisms
      underlying the lateralization of motor control.

PMID- 22989472
TI  - Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not
      accelerate neoplasia in carcinogen treated mice.
AB  - INTRODUCTION: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2)
      are secreted in parallel from the intestinal endocrine cells after nutrient
      intake. GLP-1 is an incretin hormone and analogues are available for the
      treatment of type 2 diabetes mellitus (T2DM). GLP-2 is an intestinal growth
      hormone and is shown to promote growth of colonic adenomas in carcinogen treated
      mice. Both peptides are degraded by dipeptidyl peptidase-4 (DPP-4) into inactive
      metabolites. DPP-4 inhibitors are therefore also in use for treatment of T2DM. It
      is possible that DPP-4 inhibition by enhancing the exposure of endogenous GLP-2
      to the intestinal epithelia also might mediate growth and promote neoplasia. We
      investigated the intestinal growth effect of the GLP-1 receptor agonists (GLP-1
      RAs) (liraglutide and exenatide) and DPP-4 inhibition (sitagliptin) in healthy
      mice. We also investigated the potential tumour promoting effect of liraglutide
      and sitaglitin in the colon of carcinogen treated mice. We used GLP-2 as a
      positive control. METHODS: For the growth study we treated healthy CD1 mice with
      liraglutide (300 MUg*2), exenatide (12.5 MUg*2) or vehicle subcutaneously and
      sitagliptin (8mg*2) or water by oral gavage for 10 or 30 days. We measured
      intestinal weight, cross sectional area, villus height and crypt depth. For the
      tumour study we treated carcinogen treated mice (1,2 dimethylhydrazine 21
      mg/kg/week for 12 weeks) with liraglutide (300 MUg*2), Gly2-GLP-2 (25 MUg*2) or
      vehicle subcutaneously and sitagliptin (8 mg*2) or water by oral gavage for 45
      days. We counted aberrant crypt foci (ACF), mucin depleted foci (MDF) and
      adenomas in the colon. Using COS-7 cells transfected with a GLP-2 receptor, we
      tested if liraglutide or exenatide could activate the receptor. RESULTS: In the
      10 days experiment the relative small intestinal weight was increased with 56% in
      the liraglutide group (p<0.001) and 26% in the exenatide group (p<01) compared
      with vehicle treated mice. After 30 days of treatment, liraglutide did also
      increase the colonic weight (p<0.01). By morphometry the growth pattern mimicked
      that of GLP-2. Sitagliptin treatment had only a minor effect. In the carcinogen
      treated mice we found no increase of ACF in any of the groups, the numbers of MDF
      and adenomas after liraglutide and sitagliptin treatments were similar to their
      respective control groups. Neither liraglutide nor exenatide stimulated cAMP
      release from GLP-2 receptor transfected cells. CONCLUSION: Both GLP-1 analogues
      were potent growth stimulators of the healthy mouse intestine. No agonism was
      found for GLP-1 RAs at the GLP-2 receptor. Despite of the growth effect,
      liraglutide did not promote dysplasia in the colon. Sitagliptin did not show any
      tumour promoting effects, and non considerable growth effects.

PMID- 22989474
TI  - Relationship between hydrogen sulfide levels and HDL-cholesterol, adiponectin,
      and potassium levels in the blood of healthy subjects.
AB  - Hydrogen sulfide (H(2)S) is an important signaling molecule whose blood levels
      have been shown to be lower in certain disease states. Increasing evidence
      indicates that H(2)S plays a potentially significant role in many biological
      processes and that malfunctioning of H(2)S homeostasis may contribute to the
      pathogenesis of vascular inflammation and atherosclerosis. This study examined
      the fasting blood levels of H(2)S, HDL-cholesterol, LDL-cholesterol,
      triglycerides, adiponectin, resistin, and potassium in 36 healthy adult
      volunteers. There was a significant positive correlation between blood levels of
      H(2)S and HDL-cholesterol (r = 0.49, p = 0.003), adiponectin (r = 0.36, p =
      0.04), and potassium (r = 0.34, p = 0.047), as well as a significant negative
      correlation with LDL/HDL levels (r = -0.39, p = 0.02). This is the first
      demonstration of an association of circulating levels of H(2)S with the HDL, LDL,
      and adiponectin homeostasis in the blood of healthy humans.

PMID- 22989475
TI  - Can intake of extra antioxidants delay the development and progression of
      atherosclerosis?

PMID- 22989476
TI  - Reduced regulatory T cells are associated with higher levels of Th1/TH17
      cytokines and activated MAPK in type 1 bipolar disorder.
AB  - Bipolar disorder (BD) has been associated with an immunologic imbalance shown by
      increased peripheral inflammatory markers. The underlying mechanisms of this
      phenomenon may include changes in circulating cells and differential activation
      of mitogen-activated protein kinases (MAPKs). Twenty-seven euthymic female
      subjects with BD type I (all medicated) and 24 age- and sex-matched controls were
      recruited in this study. Lymphocytes were isolated and stimulated in vitro to
      assess Th1/Th17/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-gamma and TNF
      alpha) and MAPK phosphorylation. The expression of phospho-MAPKs, a large panel
      of lymphocyte subsets and cytokines were assessed by multi-color flow cytometry.
      BD patients had reduced proportions of natural T regulatory cells (CD4+ CD25+
      FoxP3+) (p<0.01) in parallel to higher cytokine production (all p<0.01) than
      healthy controls. In particular, BD was associated with a strong bias to Th1
      rather than Th2 profile. There was an expansion of senescence-associated cells
      (CD8+ CD28-) in BD (p<0.0001). T cells of BD patients had an increased p-ERK
      signaling (p<0.0001), indicating lymphocyte activation. Our data suggest that
      multiple molecular and cellular mechanisms may contribute to the immunologic
      imbalance observed in BD. In addition, our data concur to an early senescence
      process in these patients.

PMID- 22989477
TI  - Healthy conversation skills: increasing competence and confidence in front-line
      staff.
AB  - OBJECTIVE: (i) To assess change in confidence in having conversations that
      support parents with healthy eating and physical activity post-training. (ii) To
      assess change in staff competence in using 'open discovery' questions (those
      generally beginning with 'how' and 'what' that help individuals reflect and
      identify barriers and solutions) post-training. (iii) To examine the relationship
      between confidence and competence post-training. DESIGN: A pre-post evaluation of
      'Healthy Conversation Skills', a staff training intervention. SETTING: Sure Start
      Children's Centres in Southampton, England. SUBJECTS: A total of 145 staff
      working in Sure Start Children's Centres completed the training, including play
      workers (43%) and community development or family support workers (35%). RESULTS:
      We observed an increase in median confidence rating for having conversations
      about healthy eating and physical activity (both P < 0.001), and in using 'open
      discovery' questions (P < 0.001), after staff attended the 'Healthy Conversation
      Skills' training. We also found a positive relationship between the use of 'open
      discovery' questions and confidence in having conversations about healthy eating
      post-training (r = 0.21, P = 0.01), but a non-significant trend was observed for
      having conversations about physical activity (r = 0.15, P = 0.06). CONCLUSIONS:
      The 'Healthy Conversation Skills' training proved effective at increasing the
      confidence of staff working at Sure Start Children's Centres to have more
      productive conversations with parents about healthy eating. Wider implementation
      of these skills may be a useful public health nutrition capacity building
      strategy to help community workers support families with young children to eat
      more healthy foods.

PMID- 22989478
TI  - Influence of reported study design characteristics on intervention effect
      estimates from randomised controlled trials: combined analysis of meta
      epidemiological studies.
AB  - BACKGROUND: The design of randomised controlled trials (RCTs) should incorporate
      characteristics (such as concealment of randomised allocation and blinding of
      participants and personnel) that avoid biases resulting from lack of
      comparability of the intervention and control groups. Empirical evidence suggests
      that the absence of such characteristics leads to biased intervention effect
      estimates, but the findings of different studies are not consistent. OBJECTIVES:
      To examine the influence of unclear or inadequate random sequence generation and
      allocation concealment, and unclear or absent double blinding, on intervention
      effect estimates and between-trial heterogeneity, and whether or not these
      influences vary with type of clinical area, intervention, comparison and outcome
      measure. DATA SOURCES AND METHODS: Data were combined from seven contributing
      meta-epidemiological studies (collections of meta-analyses in which trial
      characteristics are assessed and results recorded). The resulting database was
      used to identify and remove overlapping meta-analyses. Outcomes were coded such
      that odds ratios < 1 correspond to beneficial intervention effects. Outcome
      measures were classified as mortality, other objective or subjective. We examined
      agreement between assessments of trial characteristics in trials assessed in more
      than one contributing study. We used hierarchical Bayesian bias models to
      estimate the effect of trial characteristics on average bias [quantified as
      ratios of odds ratios (RORs) with 95% credible intervals (CrIs) comparing trials
      with and without a characteristic] and in increasing between-trial heterogeneity.
      RESULTS: The analysis data set contained 1973 trials included in 234 meta
      analyses. Median kappa statistics for agreement between assessments of trial
      characteristics were: sequence generation 0.60, allocation concealment 0.58 and
      blinding 0.87. Intervention effect estimates were exaggerated by an average 11%
      in trials with inadequate or unclear (compared with adequate) sequence generation
      (ROR 0.89, 95% CrI 0.82 to 0.96); between-trial heterogeneity was higher among
      such trials. Bias associated with inadequate or unclear sequence generation was
      greatest for subjective outcomes (ROR 0.83, 95% CrI 0.74 to 0.94) and the
      increase in heterogeneity was greatest for such outcomes [standard deviation (SD)
      0.20, 95% CrI 0.03 to 0.32]. The effect of inadequate or unclear (compared with
      adequate) allocation concealment was greatest among meta-analyses with a
      subjectively assessed outcome intervention effect (ROR 0.85, 95% CrI 0.75 to
      0.95), and the increase in between-trial heterogeneity was also greatest for such
      outcomes (SD 0.20, 95% CrI 0.02 to 0.33). Lack of, or unclear, double blinding
      (compared with double blinding) was associated with an average 13% exaggeration
      of intervention effects (ROR 0.87, 95% CrI 0.79 to 0.96), and between-trial
      heterogeneity was increased for such studies (SD 0.14, 95% CrI 0.02 to 0.30).
      Average bias (ROR 0.78, 95% CrI 0.65 to 0.92) and between-trial heterogeneity (SD
      0.37, 95% CrI 0.19 to 0.53) were greatest for meta-analyses assessing subjective
      outcomes. Among meta-analyses with subjectively assessed outcomes, the effect of
      lack of blinding appeared greater than the effect of inadequate or unclear
      sequence generation or allocation concealment. CONCLUSIONS: Bias associated with
      specific reported study design characteristics leads to exaggeration of
      beneficial intervention effect estimates and increases in between-trial
      heterogeneity. For each of the three characteristics assessed, these effects were
      greatest for subjectively assessed outcomes. Assessments of the risk of bias in
      RCTs should account for these findings. Further research is needed to understand
      the effects of attrition bias, as well as the relative importance of blinding of
      patients, care-givers and outcome assessors, and thus separate the effects of
      performance and detection bias. FUNDING: National Institute for Health Research
      Health Technology Assessment programme.

PMID- 22989479
TI  - New brace design combining CAD/CAM and biomechanical simulation for the treatment
      of adolescent idiopathic scoliosis.
AB  - BACKGROUND: A numerical based brace design platform, including biomechanical
      simulation, Computer Aided Design and Computer Aided Manufacturing (CAD/CAM) was
      developed to rationalize braces for the treatment of adolescent idiopathic
      scoliosis. The objective of this study was to test the feasibility of the
      approach and assess the effectiveness of braces issued from this platform as
      compared to standard brace design. METHODS: The biomechanical finite element
      model was built using the 3D reconstruction of the trunk skeleton from bi-planar
      radiographs and of the torso surface from surface topography. The finite element
      model is linked to a CAD/CAM software (Rodin4D), allowing the iterative design
      and simulation of the correction provided by the brace, as well as predicting
      pressures exerted on the torso. The resulting brace design was then fabricated
      using a numerical controlled carver. A brace designed using this platform (New
      Brace) as well as a standard thoraco-lumbo-sacral orthosis (Standard Brace) were
      built for six scoliotic patients. Both brace effectiveness was assessed using
      radiographs and compared to the simulations. FINDINGS: The New Brace corrected on
      average the spine deformities within 5 degrees  of Cobb angle of the simulated
      correction and with a similar correction as compared to the Standard Brace
      (average correction of 16 degrees  vs. 11 degrees  (MT); P=0.1 and 13 degrees 
      vs. 16 degrees  (TL/L); P=0.5 for the Standard Brace and the New Brace
      respectively). The two braces had a similar 10 degrees  lordosing effect of the
      thoracic curve. The coronal balance was quite similar (7.3 vs. 6.8mm balance
      improvement respectively for New Brace vs. Standard Brace). INTERPRETATION: These
      first clinical results showed the feasibility of building computer-assisted
      braces, equivalent to standard orthosis. An extended study on more cases is under
      way to fully assess this new design paradigm, which in the long term would allow
      improving brace design and rationalize the conservative treatments of scoliosis.

PMID- 22989480
TI  - Resolution of refractory uveitis, switching anti-TNF treatment.

PMID- 22989481
TI  - Liganded vitamin D receptor displays anti-hypertrophic activity in the murine
      heart.
AB  - Vitamin D and its analogs have been suggested to have palliative effects in the
      cardiovascular system. We have examined the effects of co-administration of the
      vitamin D receptor agonist, paricalcitol, on the hypertension, cardiac
      hypertrophy and interstitial fibrosis produced by chronic angiotensin II (AII)
      infusion. Administration of AII (800ng/kg/min) over a 14-day period resulted in
      increased blood pressure, myocyte hypertrophy, activation of the hypertrophic
      fetal gene program (atrial natriuretic peptide, B-type natriuretic peptide and
      alpha skeletal actin gene expression), increased expression of the pro
      hypertrophic modulatory calcineurin inhibitor protein 1 (MCIP 1), and increased
      fibrosis with augmented procollagen 1 and 3 gene expression. In each case co
      administration of paricalcitol (300ng/kg intraperitoneally every 48h) at least
      partially reversed the AII-dependent effect. These studies demonstrate that the
      liganded vitamin D receptor possesses potent anti-hypertrophic activity in this
      non-renin-dependent model of cardiac hypertrophy. The anti-hypertrophic activity
      appears to be at least partially intrinsic to the cardiac myocyte and may involve
      suppression of the MCIP 1 protein. This article is part of a Special Issue
      entitled 'Vitamin D Workshop'.

PMID- 22989482
TI  - Vitamin D metabolism and action in human marrow stromal cells: effects of chronic
      kidney disease.
AB  - Human marrow stromal cells (hMSCs) are targets of 1alpha,25-dihydroxyvitamin D
      [1alpha,25(OH)2D3] action to promote their differentiation to osteoblasts, but
      they also participate in vitamin D metabolism by converting 25-dihydroxyvitamin
      D3 [25(OH)D3] to 1alpha,25(OH)2D3 by 1alpha-hydroxylase (CYP27B1). Chronic kidney
      disease (CKD) is associated with impaired renal biosynthesis of 1alpha,25(OH)2D,
      low bone mass, and increased fracture risk. We tested whether CKD influences
      hMSCs' responses to vitamin D3 metabolites. The hMSCs were obtained from tissues
      discarded during arthroplasty for hip osteoarthrosis, including a subject who had
      been undergoing hemodialysis for 2+ years. There was a significant positive
      correlation between in vitro stimulation of osteoblastogenesis (alkaline
      phosphatase activity) by 1alpha,25(OH)2D3 and subjects' estimated glomerular
      filtration rate (eGFR, r=0.47, p=0.015, n=26, 56-83 years of age).
      Osteoblastogenesis was stimulated in hMSCs from both the hemodialysis and control
      subjects by 1alpha,25(OH)2D3 (10MUM), 25(OH)D3 (100MUM), or D3 (1000MUM). Thus,
      vitamin D metabolism may play an autocrine/paracrine role in osteoblast
      differentiation of hMSCs. These findings suggest that in CKD patients 25(OH)D
      sufficiency may play an important role in skeletal health; osteoblastic bone
      formation in CKD patients may not be optimal unless there is sufficient serum
      25(OH)D substrate for the MSCs to synthesize and respond to local
      1alpha,25(OH)2D. This article is part of a Special Issue entitled 'Vitamin D
      Workshop'.

PMID- 22989483
TI  - Modulation of osteoclastic migration by metabolism of 25OH-vitamin D3.
AB  - We have reported the metabolism of 25(OH) vitamin D3 (25D) into active
      1alpha,25(OH)2 vitamin D3 (1,25D) by osteoclasts derived from human peripheral
      blood mononuclear cells (PBMC), RAW 264.7cells or giant cell tumor of bone (GCT),
      which appears to optimize osteoclast differentiation but inhibit their activity.
      In this study, to elucidate the mechanism by which 25D reduces osteoclast
      resorption, we further examined the effect of 25D on osteoclast function by using
      GCT-derived osteoclasts. 25D treated cells on dentine slices resulted in
      decreased resorption volume and depth in 3D image analysis. Tartrate-resistant
      acid phosphatase (TRAP) has been reported to enhance the dephosphorylation of
      substrate binding proteins, resulting in reduced osteoclast attachment.
      Therefore, we next investigated the effect of 25D on cell migration. Treatment of
      GCT cells with 25D augmented cell migration, as determined by live cell imaging.
      These observations suggest that 25D metabolism by osteoclasts reduces their
      resorptive capacity, in part by modifying their surface adhesion and migration
      properties. This article is part of a Special Issue entitled "Vitamin D
      Workshop".

PMID- 22989484
TI  - 1,25-Dihydroxyvitamin D3 and the aging-related forkhead box O and sestrin
      proteins in osteoblasts.
AB  - Forkhead Box O (FoxO) transcription factors and Sestrins (SESN) are highly
      conserved and related stress-responsive proteins that protect the organism
      against age-related pathologies. For FoxOs, growing evidence shows a crucial role
      in osteoblast function. Here we investigated the role of different FoxO and SESN
      isoforms in 1,25(OH)2D3-treated MC3T3-E1 osteoblasts. 1,25(OH)2D3 rapidly and
      strongly induced the expression of SESN1 and FoxO3a but down-regulated the
      expression of SESN3 and FoxO1. SESN2 and FoxO4 levels were hardly affected by
      1,25(OH)2D3. Chromatin Immunoprecipitation (ChIP)-sequencing revealed significant
      VDR/RXR binding to a DR3-type VDRE in SESN1 but not in the genomic region where
      FoxO3a is located. Mutation of the SESN1 VDRE abolished responsiveness to
      1,25(OH)2D3 in luciferase-based transfection assays. siRNA-mediated knock-down of
      SESN1, SESN3, FoxO1 or FoxO3a did not prevent 1,25(OH)2D3 from reducing the
      expression of cell cycle markers like Cyclin D1 and Cdc6 and from exerting its
      characteristic antiproliferative effect on MC3T3-E1 osteoblasts. Accordingly, the
      1,25(OH)2D3-induced reduction in the number of S-phase cells was also maintained.
      The antiproliferative effect was still present in primary osteoblast in which all
      three FoxO isoforms were deleted (TKOpOB). Interestingly, both MC3T3-E1
      osteoblasts in which FoxO1 was knocked-down and TKOpOBs accumulated significantly
      more reactive oxygen species (ROS) after treatment with 1,25(OH)2D3 than control
      cells. siRNA-mediated knock-down of individual SESN isoforms did not result in
      significant differences in ROS levels. In conclusion, 1,25(OH)2D3 directly and
      indirectly alters the expression levels of different FoxO and SESN isoforms in
      osteoblasts, presumably not to exert its antiproliferative action but to control
      ROS levels. This article is part of a Special Issue entitled 'Vitamin D
      Workshop'.

PMID- 22989485
TI  - Incidental finding of partial anomalous pulmonary venous drainage.

PMID- 22989486
TI  - Effects of osmotic and cold shock on adherent human mesenchymal stem cells during
      cryopreservation.
AB  - Cryopreservation is one of the most practical methods for the long-term storage
      of cell-matrix systems to ensure off-shelf availability in tissue engineering,
      stem cell therapy and drug testing. The aim of this study is to investigate the
      effects of osmotic and cold shock caused by the procedures of cryoprotectant
      agent addition/removal and freezing during cryopreservation on cell viability,
      intracellular properties, such as filamentous actin distribution, mitochondria
      localization and intracellular pH, and further recovery of adherent human
      mesenchymal stem cells. Our results shows a significant decrease in cell
      viability around 30% after cryopreservation at the cooling rates of 1, 5 and 10
      degrees C/min in comparison to the adherent cells and the cells in suspension,
      implicating that the adherent cells are more vulnerable than the suspension
      cells. The osmotic shock and cold shock induced by freezing lead to dramatic
      changes in the intracellular properties. The cooling rate of 10 degrees C/min
      results in acidification of intracellular pH, distortion and accumulation of
      filamentous actin, and aggregation of mitochondria. Our findings also suggest
      that the cooling rate of 1 degrees C/min helps to maintain cell morphology and
      attachment, integrity and uniformity of filamentous actin, and leads to better
      cell recovery after cryopreservation.

PMID- 22989487
TI  - Separation of alkali metals using isotachophoresis with cryptand 222 as a leading
      electrolyte additive.
AB  - This work shows how the inclusion of cryptand 222 as a leading electrolyte
      additive in isotachophoresis affects the electrophoretic mobilities of alkali
      metal cations. Using isotachophoresis the separation of alkali metals can be
      difficult due to the similar electrophoretic mobilities of three of the ions:
      caesium, rubidium and potassium. However, the presence of cryptand 222 in the
      leading electrolyte retards the mobilities of the caesium, rubidium and potassium
      to a different extent allowing separations to be made. A novel electrolyte system
      was formulated which consisted of a leading electrolyte of 10 mM caesium
      hydroxide, 0.75 mM cryptand 222 buffered to pH 9.4 with glycylglycine and a
      terminating electrolyte of 10 mM tetrabutylammonium hydroxide. The use of this
      electrolyte system allowed good separations of mixtures of rubidium, potassium,
      sodium and lithium to be achieved. The method was also applied to the analysis of
      edible salt samples.

PMID- 22989488
TI  - Maximizing the speed of separations for industrial problems.
AB  - Recent improvement efforts in chromatography have provided great improvements in
      the rate of plate production, but less attention has been spent on optimizing the
      kinds of problems that are most often encountered in industry. When factors are
      not independent in their effects on the responses of a chromatographic
      separation, all adjustable factors must be considered in concert in seeking the
      best or optimum condition that solves the problem. This requires careful
      attention to specifying the goals, the adjustable factors, and the constraints
      required to make sure the outcome can actually be implemented. Strategies for
      optimizing assay and screening methods in the context of industrial needs are
      presented. Expanding the factor space of the system being investigated can lead
      to better outcomes. The prospect of adding column-outlet pressure control and
      expanding the mobile phase composition to include condensed gases or
      supercritical fluids is explored. Reversed-phase liquid chromatography,
      hydrophilic interaction chromatography, electrostatic repulsion hydrophilic
      interaction chromatography, and supercritical fluid chromatography are contiguous
      with regard to mobile phase characteristics. Adjustment of selectivity through
      instrument-controlled factors can benefit method development. Opportunities
      obtained by blending modifiers, varying temperature and pressure with
      compressible mobile phases, and controlling pH are discussed in the context of
      optimizing methods.

PMID- 22989489
TI  - A new accurate quadratic equation model for isothermal gas chromatography and its
      comparison with the linear model.
AB  - The gas holdup time (tM) is a dominant parameter in gas chromatographic retention
      models. The difference equation (DE) model proposed by Wu et al. (J. Chromatogr.
      A 2012, http://dx.doi.org/10.1016/j.chroma.2012.07.077) excluded t(M). In the
      present paper, we propose that the relationship between the adjusted retention
      time t'RZ and carbon number z of n-alkanes follows a quadratic equation (QE) when
      an accurate tM is obtained. This QE model is the same as or better than the DE
      model for an accurate expression of the retention behavior of n-alkanes and model
      applications. The QE model covers a larger range of n-alkanes with better curve
      fittings than the linear model. The accuracy of the QE model was approximately 2
      6 times better than the DE model and 18-540 times better than the LE model.
      Standard deviations of the QE model were approximately 2-3 times smaller than
      those of the DE model.

PMID- 22989490
TI  - Dietary patterns are associated with insulin resistance in Chinese adults without
      known diabetes.
AB  - The aim of the present study was to examine the association between dietary
      patterns and insulin resistance in Chinese adults without known diabetes. Study
      subjects were 1070 Chinese adults aged 18 years and above in Jiangsu Province who
      participated in the 2006 wave of the China Health and Nutrition Survey. Usual
      dietary intake was assessed by using a validated FFQ. Dietary patterns were
      identified by factor analysis using a principal component analysis method.
      Insulin resistance was defined as the highest quartile of the homeostasis model
      assessment of insulin resistance (HOMA-IR) scores. We derived four dietary
      patterns in our population by factor analysis: the Western, High-wheat,
      Traditional and Hedonic pattern. After adjusted for potential confounders, the
      Western pattern was significantly associated with greater odds for insulin
      resistance (P for trend = 0.009), while a significant negative association was
      found between the Hedonic pattern and insulin resistance (P for trend = 0.035).
      Compared with the lowest quartile of the Western pattern, the highest quartile
      had higher odds of insulin resistance (adjusted OR 1.89, 95 % CI 1.12, 3.19).
      There was a 42 % decrease in the odds after adjustment for all covariates in the
      highest quartile of the Hedonic pattern, compared with the lowest quartile
      (adjusted OR 0.58, 95 % CI 0.34, 0.99). HOMA-IR levels as a continuous variable
      also increased across the quartiles of the Western pattern and decreased across
      the quartiles of the Hedonic pattern. In conclusion, dietary patterns were
      significantly associated with insulin resistance in Chinese adults without known
      diabetes.

PMID- 22989491
TI  - Realist randomised controlled trials: a new approach to evaluating complex public
      health interventions.
AB  - Randomized trials of complex public health interventions generally aim to
      identify what works, accrediting specific intervention 'products' as effective.
      This approach often fails to give sufficient consideration to how intervention
      components interact with each other and with local context. 'Realists' argue that
      trials misunderstand the scientific method, offer only a 'successionist' approach
      to causation, which brackets out the complexity of social causation, and fail to
      ask which interventions work, for whom and under what circumstances. We counter
      argue that trials are useful in evaluating social interventions because
      randomized control groups actually take proper account of rather than bracket out
      the complexity of social causation. Nonetheless, realists are right to stress
      understanding of 'what works, for whom and under what circumstances' and to argue
      for the importance of theorizing and empirically examining underlying mechanisms.
      We propose that these aims can be (and sometimes already are) examined within
      randomized trials. Such 'realist' trials should aim to: examine the effects of
      intervention components separately and in combination, for example using multi
      arm studies and factorial trials; explore mechanisms of change, for example
      analysing how pathway variables mediate intervention effects; use multiple trials
      across contexts to test how intervention effects vary with context; draw on
      complementary qualitative and quantitative data; and be oriented towards building
      and validating 'mid-level' program theories which would set out how interventions
      interact with context to produce outcomes. This last suggestion resonates with
      recent suggestions that, in delivering truly 'complex' interventions, fidelity is
      important not so much in terms of precise activities but, rather, key
      intervention 'processes' and 'functions'. Realist trials would additionally
      determine the validity of program theory rather than only examining 'what works'
      to better inform policy and practice in the long-term.

PMID- 22989492
TI  - Replicating MISTERS: an epidemiological criminology framework analysis of a
      program for criminal justice-involved minority males in the community.
AB  - The Men in STD Training and Empowerment Research Study (MISTERS) program and
      epidemiological criminology began their development in Atlanta at about the same
      time. MISTERS focuses on men recently released from jail to reduce both HIV/STD
      and crime-related risk factors through a brief educational intervention. This
      article examines ways in which MISTERS and epidemiological criminology have been
      used to inform one another in the replication of the MISTERS program in Orange
      County, Florida. Data from 110 MISTERS participants during the first 10 months of
      operation are analyzed to examine the overlapping occurrence of health and
      criminal risk behaviors in the men's lives. This provides a test of core
      hypotheses from the epidemiological criminology framework. This article also
      examines application of the epidemiological criminology framework to develop
      interventions to address health and crime risk factors simultaneously in Criminal
      Justice-Involved populations in the community.

PMID- 22989493
TI  - Syphilis outbreak at a California men's prison, 2007-2008: propagation by lapses
      in clinical management, case management, and public health surveillance.
AB  - This field report describes an investigation to identify cases to control a
      syphilis outbreak in a prison and determine whether clinical, case management,
      and surveillance practices influenced the outbreak occurrence, detection, or
      management. Key performance measures were assessed to evaluate timeliness and
      quality of clinical and case management activities and surveillance practices.
      Thirty cases were found. Prior to the investigation, median times for clinical
      and reporting/surveillance measures were 15 days from primary and secondary (P&S)
      symptom onset to exam, 7 days from P&S exam to treatment, and 63 days from
      serologic test to the state's receipt of case. After the investigation, these
      measures improved to 8, 4.5, and 28 days, respectively. Lack of adherence to
      surveillance and clinical management protocols likely contributed to this
      outbreak, which was curtailed by aggressive control measures.

PMID- 22989494
TI  - Validation of the Italian version of Mini-ICF-APP, a short instrument for rating
      activity and participation restrictions in psychiatric disorders.
AB  - Aims. The assessment of limitations in social capacities can be done with the
      Mini-ICF-APP, a rating scale built in reference to the International
      Classification of Functioning, Disability and Health (ICF). The aim of this study
      was to assess the reliability and the convergent validity of the Italian version
      of this scale. Methods. We recruited 120 consecutive patients diagnosed with
      schizophrenia, major depression, bipolar I disorder and anxiety disorders.
      Included measures were the Brief Psychiatric Rating Scale (BPRS), the Clinical
      Global Impression Scale (CGI-S), the Personal and Social Performance Scale (PSP)
      and the Social and Occupational Functioning Assessment Scale (SOFAS). Results.
      The median CGI-S and BPRS scores were 5 and 16.5. Mean Mini-ICF-APP total score
      was 18.1. Schizophrenics' Mini-ICF-APP score was higher, while that of anxious
      patients was lower than in the other diagnoses. Intra-class correlations (ICC)
      revealed a significant inter-rater agreement for total score (ICC 0.987) and for
      each item of the Mini-ICF-APP. The test-retest agreement was also highly
      significant (ICC 0.993). The total score of the Mini-ICF-APP obtained good
      negative correlations with PSP (r s = -0.767) and with SOFAS scores (r s = 
      0.790). The distribution items of the Mini-ICF-APP showed some skewness,
      indicating that self-care (item 12) and mobility (item 13) were amply preserved
      in most patients. The Mini-ICF-APP total score was significantly correlated with
      both CGI-S (r s = 0.777) and BPRS (r s = 0.729). Conclusions. As a short
      instrument, the Mini-ICF-APP scale seems to be well suited to everyday
      psychiatric practice as a means of monitoring changes in psychosocial
      functioning, in particular in schizophrenic patients.

PMID- 22989495
TI  - Dosimetric assessment and characterisation of the neutron field around a Howitzer
      container using a Bonner sphere spectrometer, Monte Carlo simulations and the
      NSDann and NSDUAZ unfolding codes.
AB  - The Neutron Measurements Laboratory at the Nuclear Engineering Department of the
      Polytechnic University of Madrid consists of a bunker-like room and was built for
      neutron dosimetry research purposes and measurements. The facility includes a 74
      GBq 241Am-Be neutron source placed inside a neutron Howitzer container. The
      source can be moved to the irradiation or to the storage position. In this work,
      a Bonner sphere spectrometer (BSS) was used to measure the neutron fluence
      spectra with the source in both positions. Ambient dose equivalent rates, *(10),
      were measured using a calibrated neutron area monitor LB6411 (Berthold). The
      measured count rates were used as input to the NSDann and NSDUAZ unfolding
      programs to obtain the neutron fluence spectra and *(10). Monte Carlo (MC)
      simulation methods were used to model the system and to calculate the neutron
      fluence rate and the ambient dose equivalent rate at the measurement points. The
      comparison between NSDUAZ and NSDann resulted in relative deviations up to 6.87 %
      in the total neutron fluence rate and 7.18 % in *(10) values, despite the
      differences in the shape of the spectra obtained for the irradiation position.
      Comparing with the measured values, the *(10) values obtained with the unfolding
      programs exhibit a maximum relative deviation of 12.19 %. Taking into account the
      associated uncertainties, MC simulations seem to be in reasonable agreement with
      measurements. A maximum relative deviation of 15.65 % between computed and
      measured *(10) values was obtained. The computed count rates were applied to the
      unfolding programs to calculate the total neutron fluence rate and a maximum
      deviation of 12.83 % was obtained between the original values calculated by
      NSDann. A sensitivity test showed that the NSDann unfolding program is very
      sensitive to the uncertainties of the BSS count rates.

PMID- 22989496
TI  - Effect of passive immunization against leptin on ovarian follicular development
      in prepubertal mice.
AB  - Leptin has been demonstrated to be essential for reproduction. However, all the
      relevant studies reported to date have investigated either the effect of a
      complete absence of leptin both centrally and peripherally, or excess leptin
      administration. The aim of this present study was to investigate the effect of
      reducing peripheral leptin concentrations on ovarian follicular development in
      prepubertal animals via administration of an anti-leptin antibody. Pre-pubertal
      female mice were administered anti-leptin antibody under the skin behind the head
      for four days, with or without gonadotropins, and ovaries were weighed and
      collected for follicle counting. Control animals were treated with non-immune
      serum. Passive immunization against leptin, with or without gonadotropins,
      resulted in a significant increase in ovarian weight compared with control
      ovaries. Furthermore, the ovaries from the anti-leptin group had significantly
      greater numbers of primary follicles per ovarian section than the control group,
      thus suggesting an increase in the transition of primordial to primary follicles
      after treatment. Interestingly, animals treated with anti-leptin plus
      gonadotropins had a significantly higher number of Graafian follicles in their
      ovaries compared with the other groups. Collectively, the results of the present
      study indicate that reduction of leptin in the circulation promotes ovarian
      follicle development in female mice, suggesting that peripheral leptin acts as an
      inhibitor of ovarian follicle development.

PMID- 22989497
TI  - Association of interleukin-10G microsatellite polymorphism with the
      susceptibility of ankylosing spondylitis.

PMID- 22989498
TI  - Acute cognitive effects of high doses of dextromethorphan relative to triazolam
      in humans.
AB  - BACKGROUND: Although concerns surrounding high-dose dextromethorphan (DXM) abuse
      have recently increased, few studies have examined the acute cognitive effects of
      high doses of DXM. The aim of this study was to compare the cognitive effects of
      DXM with those of triazolam and placebo. METHODS: Single, acute, oral doses of
      DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5mg/70
      kg), and placebo were administered p.o. to twelve healthy volunteers with
      histories of hallucinogen use, under double-blind conditions, using an ascending
      dose run-up design. Effects on cognitive performance were examined at baseline
      and after drug administration for up to 6h. RESULTS: Both triazolam and DXM
      produced acute impairments in attention, working memory, episodic memory, and
      metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were
      generally smaller in magnitude than those observed after 0.5mg/70 kg triazolam.
      Doses of DXM that impaired performance to the same extent as triazolam were in
      excess of 10-30 times the therapeutic dose of DXM. CONCLUSION: The magnitude of
      the doses required for these effects and the absence of effects on some tasks
      within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad
      therapeutic window of over-the-counter DXM preparations when used appropriately.
      However, the administration of supratherapeutic doses of DXM resulted in acute
      cognitive impairments on all tasks that were examined. These findings are likely
      relevant to cases of high-dose DXM abuse.

PMID- 22989499
TI  - The relationship between alcohol use and injecting drug use: impacts on health,
      crime and wellbeing.
AB  - BACKGROUND AND OBJECTIVES: People who inject drugs (PWID) are at risk of a
      variety of adverse outcomes. Previous research suggests that alcohol, when
      consumed with opioids, is a risk factor for overdose, but there has been less
      investigation of the effects of alcohol consumption on other health, criminogenic
      or life satisfaction outcomes. In this paper we explore the effects of alcohol on
      outcomes for PWID across a variety of life domains. METHODS: Baseline data were
      drawn from the Melbourne Injecting Drug User cohort study, which is a cohort of
      688 PWID. Drinking scores were generated from the AUDIT-C (0, 1-7, 8+) and
      associations between them and health (recent heroin overdose, Emergency
      Department use), criminogenic (violent and nonviolent crime) and life
      satisfaction (personal wellbeing) outcomes were examined using logistic and
      linear regression. RESULTS: While around 36% of the cohort reported past-month
      abstinence from alcohol, 44% scored between 1 and 7 and 20% above 7 on the AUDIT
      C. A score above 7 was associated with perpetration of violent crime and lower
      personal wellbeing ratings than a score of 0, after adjusting for potential
      confounders. There was no association between alcohol and other outcomes
      examined, after adjustment for confounders. CONCLUSION: Cohort participants who
      drink heavily were more likely to report engaging in violent crime and poorer
      life satisfaction. The relationship between alcohol and the offending behaviours
      of the cohort was consistent with the effects of alcohol on violent offending in
      the broader community.

PMID- 22989500
TI  - Minimally invasive surgery for spontaneous supratentorial intracerebral
      hemorrhage: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: There has been a nonstandard surgical procedure and
      extensive international controversy in minimally invasive surgery (MIS) for the
      management of spontaneous supratentorial intracerebral hemorrhage. This meta
      analysis assessed the effectiveness of MIS as compared with other treatment
      options, including conservative medical treatment and conventional craniotomy, in
      patients with supratentorial intracerebral hemorrhage. METHODS: PubMed, Embase,
      Cochrane Controlled Trials Register (CCTR), Web of Science, European Association
      for Grey Literature Exploitation (EAGLE), National Technical Information Service
      (NTIS), Current Controlled Trials, Clinical Trials, International Clinical Trials
      Registry, Internet Stroke Center, Chinese Biomedical Literature Database (CBM),
      Chinese National Knowledge Infrastructure (CNKI) (last searched December 2011)
      were searched. Randomized controlled trials on MIS in patients with computed
      tomography-confirmed supratentorial intracerebral hemorrhage were included. We
      excluded low-quality randomized controlled trials. The death or dependence at the
      end of follow-up was defined as the primary outcome, and the death at the end of
      follow-up was defined as the secondary outcome. RESULTS: The 313 randomized
      controlled trials met the included criteria. We only analyzed 12 high-quality
      randomized controlled trials involving 1955 patients. The quality of the included
      trials was consistently high. OR of the primary outcome and secondary outcome of
      MIS both showed significant reductions (OR, 0.54, P<0.00001; OR, 0.53,
      P<0.00001). CONCLUSIONS: Patients with supratentorial intracerebral hemorrhage
      may benefit more from MIS than other treatment options. The most likely
      candidates to benefit from MIS are both sexes, age of 30 to 80 years with
      superficial hematoma, Glasgow Coma Scale score of >=9, hematoma volume between 25
      and 40 mL, and within 72 hours after onset of symptoms. Our study could help
      select appropriate patients for MIS and guide clinicians to optimize treatment
      strategies in supratentorial intracerebral hemorrhage.

PMID- 22989501
TI  - Time is brain(stem) in basilar artery occlusion.
AB  - BACKGROUND AND PURPOSE: The frequent use of a longer time window for
      recanalization therapy in patients with basilar artery occlusion (BAO) in daily
      practice is not supported by any scientific evidence. We investigated the
      relationship between time to recanalization therapy and functional outcome in BAO
      with data from the Basilar Artery International Cooperation Study (BASICS).
      METHODS: BASICS is a prospective multicenter registry of patients (n=619) with
      radiologically confirmed BAO. We analyzed patients receiving intravenous
      thrombolysis or intra-arterial treatment. Patients were divided into 4 groups
      based on the interval between estimated time of BAO and start of recanalization
      therapy: <=3 hours (n=134), >3 to <=6 hours (n=151), >6 to <=9 hours (n=56), and
      >9 hours (n=68). Primary outcome measure was poor functional outcome (modified
      Rankin scale score 4-6) after 1 month. We calculated adjusted risk ratios with
      95% CIs using Poisson regression analyses with the <=3 hours group as the
      reference group. RESULTS: Patients had an increased risk of poor functional
      outcome as time to recanalization therapy became longer (<=3 hours: 62%; >3 to
      <=6 hours: 67% [adjusted risk ratio, 1.06; 0.91-1.25]; >6 to <=9 hours: 77%
      [adjusted risk ratio, 1.26; 1.06-1.51]; >9 hours: 85% [adjusted risk ratio, 1.47;
      1.26-1.72]). CONCLUSIONS: Early recanalization therapy in patients with BAO is
      associated with a more favorable outcome with a significant increased chance of a
      poor outcome when recanalization therapy is started >6 hours after estimated time
      of BAO.

PMID- 22989502
TI  - Letter by Griebe et al regarding article, "Jugular veins in transient global
      amnesia: innocent bystanders".

PMID- 22989503
TI  - Critique of closure or medical therapy for cryptogenic stroke with patent foramen
      ovale: the hole truth?

PMID- 22989504
TI  - Gut microbiota, immune development and function.
AB  - The microbiota of Westerners is significantly reduced in comparison to rural
      individuals living a similar lifestyle to our Paleolithic forefathers but also to
      that of other free-living primates such as the chimpanzee. The great majority of
      ingredients in the industrially produced foods consumed in the West are absorbed
      in the upper part of small intestine and thus of limited benefit to the
      microbiota. Lack of proper nutrition for microbiota is a major factor under
      pinning dysfunctional microbiota, dysbiosis, chronically elevated inflammation,
      and the production and leakage of endotoxins through the various tissue barriers.
      Furthermore, the over-comsumption of insulinogenic foods and proteotoxins, such
      as advanced glycation and lipoxidation molecules, gluten and zein, and a reduced
      intake of fruit and vegetables, are key factors behind the commonly observed
      elevated inflammation and the endemic of obesity and chronic diseases, factors
      which are also likely to be detrimental to microbiota. As a consequence of this
      lifestyle and the associated eating habits, most barriers, including the gut, the
      airways, the skin, the oral cavity, the vagina, the placenta, the blood-brain
      barrier, etc., are increasingly permeable. Attempts to recondition these barriers
      through the use of so called 'probiotics', normally applied to the gut, are
      rarely successful, and sometimes fail, as they are usually applied as adjunctive
      treatments, e.g. in parallel with heavy pharmaceutical treatment, not rarely
      consisting in antibiotics and chemotherapy. It is increasingly observed that the
      majority of pharmaceutical drugs, even those believed to have minimal adverse
      effects, such as proton pump inhibitors and anti-hypertensives, in fact adversely
      affect immune development and functions and are most likely also deleterious to
      microbiota. Equally, it appears that probiotic treatment is not compatible with
      pharmacological treatments. Eco-biological treatments, with plant-derived
      substances, or phytochemicals, e.g. curcumin and resveratrol, and pre-, pro- and
      syn-biotics offers similar effects as use of biologicals, although milder but
      also free from adverse effects. Such treatments should be tried as alternative
      therapies; mainly, to begin with, for disease prevention but also in early cases
      of chronic diseases. Pharmaceutical treatment has, thus far, failed to inhibit
      the tsunami of endemic diseases spreading around the world, and no new tools are
      in sight. Dramatic alterations, in direction of a paleolithic-like lifestyle and
      food habits, seem to be the only alternatives with the potential to control the
      present escalating crisis. The present review focuses on human studies,
      especially those of clinical relevance.

PMID- 22989505
TI  - Ezetimibe inhibits PMA-induced monocyte/macrophage differentiation by altering
      microRNA expression: a novel anti-atherosclerotic mechanism.
AB  - Ezetimibe, a selective inhibitor of intestinal cholesterol absorption,
      effectively reduces plasma cholesterol both in monotherapy or combined with a
      statin. However, its effect on atherosclerosis plaque progression is certainly
      unknown. MicroRNAs are short non-encoding RNA molecules dynamically implicated in
      monocytic differentiation which is considered an essential process during
      atherosclerosis development. The purpose of this study was to investigate the
      effect of ezetimibe on monocyte/macrophage differentiation as well as the
      implication of microRNAs (miRNAs) in this process. THP-1 differentiation with PMA
      became cells adherent to the plastic surface, and induced the expression of
      macrophage surface markers (CD11a, CD11b and ICAM-1) and miR-155, miR-222, miR
      424 and miR-503. In the presence of ezetimibe, the adhesive capacity of THP-1
      cells was decreased in a dose-dependent manner (P<0.05) and the expression of
      CD11a, CD11b and ICAM-1 was almost totally inhibited (P<0.05). The expression of
      miR-155, miR-222, miR-424 and miR-503 was reduced by 55%, 100%, 75% and 100%,
      respectively (P<0.05). Further mechanistic studies demonstrated that ezetimibe
      suppressed the PMA-induced phosphorylation of ERK/MAPK and inhibited the NF
      kappaB activity, which are upstream signalling molecules in the differentiation
      process. In conclusion, ezetimibe inhibits PMA-induced THP-1 cell differentiation
      into macrophage-like cells in association with the inhibition of miRNA pathways.
      Our study suggests that inhibition of miRNAs might form a novel mechanism of anti
      atherosclerotic effect of ezetimibe.

PMID- 22989506
TI  - Coverbal gestures in the recovery from severe fluent aphasia: a pilot study.
AB  - This post hoc study investigated coverbal gesture patterns in two persons with
      chronic Wernicke's aphasia. They had both received therapy focusing on multimodal
      communication therapy, and their pre- and post-therapy verbal and gestural skills
      in face-to-face conversational interaction with their speech therapist were
      analysed by administering a partial barrier Referential Communication Task (RCT).
      The RCT sessions were reviewed in order to analyse: (a) participant coverbal
      gesture occurrence and types when in speaker role, (b) distribution of iconic
      gestures in the RCT communicative moves, (c) recognisable semantic content, and
      (d) the ways in which gestures were combined with empty or paraphasic speech. At
      post-therapy assessment only one participant showed improved communication skills
      in spite of his persistent language deficits. The improvement corresponded to
      changes on all gesturing measures, suggesting thereby that his communication
      relied more on gestural information. No measurable changes were observed for the
      non-responding participant-a finding indicating that the coverbal gesture
      measures used in this study might account for the different outcomes. These
      results point to the potential role of gestures in treatment aimed at fostering
      recovery from severe fluent aphasia. Moreover, this pattern of improvement runs
      contrary to a view of gestures used as a pure substitute for lexical items, in
      the communication of people with severe fluent aphasia. LEARNING OUTCOMES: The
      readers will describe how to assess and interpret the patterns of coverbal
      gesturing in persons with fluent aphasia. They will also recognize the potential
      role of coverbal gestures in recovery from severe fluent aphasia.

PMID- 22989507
TI  - A qualitative exploration of the health promotion effects of varying body size in
      photographs analyzed using Interpretative Phenomenological Analysis.
AB  - As levels of obesity continue to rise worldwide so do the number of public health
      campaigns designed to help address this problem with advice and information on
      how to stabilize or decrease weight. However, few studies have explored the
      influence of visual images, and specifically photographs, in weight-related
      health materials despite their widespread use in publications and online. We
      carried out qualitative individual telephone interviews with eight women who were
      actively engaged in managing their weight. They viewed a series of photographs of
      slim and overweight women demonstrating healthy behaviors such as engaging in
      physical activity or reading a food label. Responses were analyzed using
      Interpretative Phenomenological Analysis. The two core themes that emerged were
      the motivating/de-motivating effect of body size representation on health
      behavior intentions, and the social implications of being overweight.
      Participants liked and appeared motivated by the images of larger women, actively
      seeking out social comparisons. Implications of these findings in the development
      of health promotion messages are discussed.

PMID- 22989508
TI  - Virus assembly and plasma membrane domains: which came first?
AB  - Viral assembly is a key step in the virus life cycle. In this review, we focus
      mainly on the ability of retroviruses, especially HIV-1, to assemble at the
      plasma membrane of their host cells. The assembly process of RNA enveloped
      viruses necessitates a fine orchestration between the different viral components
      and specific interactions between viral proteins and lipids of the host cell
      membrane. Searching for a comparison with another RNA enveloped virus, we refer
      to influenza virus to show how it could share (or not) some common features with
      HIV-1 assembly since both viruses are believed to assemble mainly in raft
      microdomains. We also discuss the role of RNA and the cellular actin cytoskeleton
      in enhancing these viral assembly processes. Finally, based on the literature and
      on new results we have obtained by molecular docking, we propose another
      mechanism for HIV-1 assembly in membrane domains. This mechanism involves the
      trapping of acidic lipids by the viral Gag protein by means of ionic protein
      lipid interactions, inducing thereby formation of acidic lipid-enriched
      microdomains (ALEM).

PMID- 22989509
TI  - Cooking practices, air quality, and the acceptability of advanced cookstoves in
      Haryana, India: an exploratory study to inform large-scale interventions.
AB  - BACKGROUND: In India, approximately 66% of households rely on dung or woody
      biomass as fuels for cooking. These fuels are burned under inefficient
      conditions, leading to household air pollution (HAP) and exposure to smoke
      containing toxic substances. Large-scale intervention efforts need to be informed
      by careful piloting to address multiple methodological and sociocultural issues.
      This exploratory study provides preliminary data for such an exercise from Palwal
      District, Haryana, India. METHODS: Traditional cooking practices were assessed
      through semi-structured interviews in participating households. Philips and
      Oorja, two brands of commercially available advanced cookstoves with small
      blowers to improve combustion, were deployed in these households. Concentrations
      of particulate matter (PM) with a diameter <2.5 MUm (PM2.5) and carbon monoxide
      (CO) related to traditional stove use were measured using real-time and
      integrated personal, microenvironmental samplers for optimizing protocols to
      evaluate exposure reduction. Qualitative data on acceptability of advanced stoves
      and objective measures of stove usage were also collected. RESULTS: Twenty-eight
      of the thirty-two participating households had outdoor primary cooking spaces.
      Twenty households had liquefied petroleum gas (LPG) but preferred traditional
      stoves as the cost of LPG was higher and because meals cooked on traditional
      stoves were perceived to taste better. Kitchen area concentrations and kitchen
      personal concentrations assessed during cooking events were very high, with
      respective mean PM2.5 concentrations of 468 and 718 ug/m3. Twenty-four hour
      outdoor concentrations averaged 400 ug/m3. Twenty-four hour personal CO
      concentrations ranged between 0.82 and 5.27 ppm. The Philips stove was used more
      often and for more hours than the Oorja. CONCLUSIONS: The high PM and CO
      concentrations reinforce the need for interventions that reduce HAP exposure in
      the aforementioned community. Of the two stoves tested, participants expressed
      satisfaction with the Philips brand as it met the local criteria for usability.
      Further understanding of how the introduction of an advanced stove influences
      patterns of household energy use is needed. The preliminary data provided here
      would be useful for designing feasibility and/or pilot studies aimed at
      intervention efforts locally and nationally.

PMID- 22989510
TI  - Practical utility and reliability of whole-room calorimetry in young children.
AB  - The use of whole-room calorimetry (WRC) in young children can increase our
      understanding of children's energy balance. However, studies using WRC in young
      children are rare due to concerns about its feasibility. To assess the
      feasibility of WRC in young children, forty children, aged 4-6 years, were asked
      to follow a graded activity protocol while in a WRC. In addition, six children
      participated in two additional resting protocols to examine the effect of diet
      induced thermogenesis on resting energy expenditure (REE) measures and the
      reliability of REE measurement. Refusals to participate and data loss were
      quantified as measures of practical utility, and REE measured after an overnight
      fast and after a 90-min fast were compared. In addition, both were compared to
      predicted BMR values using the Schofield equation. Our results showed that thirty
      (78.9 %) participants had acceptable data for all intensities of the activity
      protocol. The REE values measured after a 90-min fast (5.07 (SD 1.04) MJ/d) and
      an overnight fast (4.73 (SD 0.61) MJ/d) were not significantly different from
      each other (P= 0.472). However, both REE after an overnight fast and a 90-min
      fast were significantly higher than predicted BMR (3.96 (SD 0.18) MJ/d) using the
      Schofield equation (P= 0.024 and 0.042, respectively). We conclude that, with a
      developmentally sensitive approach, WRC is feasible and can be standardised
      adequately even in 4- to 6-year-old children. In addition, the effect of a small
      standardised breakfast, approximately 90 min before REE measurements, is likely
      to be small.

PMID- 22989511
TI  - Role of gemcitabine-based combination therapy in the management of advanced
      pancreatic cancer: a meta-analysis of randomised trials.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death
      worldwide. Gemcitabine is the mainstay treatment for advanced disease. However,
      almost all up-to-date trials, that evaluated the benefit of gemcitabine
      combination schedules, failed to demonstrate an improvement in overall survival
      (OS). In this study, we performed a systematic review and a meta-analysis of
      randomised clinical trials (RCTs) to investigate the efficacy and safety of
      gemcitabine-based combination regimens as compared to gemcitabine alone in the
      management of pancreatic cancer. METHODS: Clinical trials were collected by
      searching different databases (PubMed, Embase and the Central Registry of
      Controlled Trials of the Cochrane Library) and abstracts from major cancer
      meetings. We considered period ranging from January 1997 to January 2012. Primary
      end-point was OS, secondary end-points were response rate (RR), disease control
      rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR
      and risk ratios of grade 3-4 toxicity rates (TRs), were extracted as presented in
      retrieved studies and used for statistical analysis. Meta-analytic estimates were
      derived using random-effects model. FINDINGS: Thirty-four trials for a total of
      10,660 patients were selected and included in the final analysis. The analysis
      showed that combination chemotherapy confers benefit in terms of OS (HR: 0.93;
      95% confidence interval (CI): 0.89-0.97; p=0.001). ORs for both RR and DCR
      demonstrated a significant advantage for combination therapy (OR for RR: 0.60,
      95%CI: 0.47-0.76, p<0.001; OR for DCR: 0.79; 95%CI: 0.66-0.93; p=0.006).
      Toxicities were more frequent with the combination treatment and significance in
      terms of risk ratio was reached for diarrhoea (0.53, 95%CI: 0.36-0.79), nausea
      (0.74, 95%CI: 0.56-0.96), neutropenia (0.71, 95%CI: 0.59-0.85) and
      thrombocytopenia (0.57, 95%CI: 0.43-0.75). INTERPRETATION: The combination
      chemotherapy as compared to gemcitabine alone significantly improves OS in
      advanced pancreatic cancer (APC). However, this advantage is marginal whereas the
      treatment-related toxicity is increased, suggesting the use of gemcitabine-based
      combination regimens only in selected patient populations. New prospective
      trials, based on translational approaches and innovative validated biomarkers,
      are eagerly awaited on this topic.

PMID- 22989512
TI  - Mandibular second molar periodontal healing after impacted third molar extraction
      in young adults.
AB  - PURPOSE: To estimate the prevalence of preoperative periodontal defects and
      analyze 12-month spontaneous healing on the distal aspect of the mandibular
      second molar (M2) after impacted mandibular third molar (M3) extraction.
      MATERIALS AND METHODS: This prospective clinical study was conducted in 25
      healthy young patients (21.03 +/- 4.38 yr old) with 40 extractions of higher-risk
      periodontal impacted M3s. Plaque and gingival indexes, recession, bleeding on
      probing, probing depth (PD), and attachment level were recorded before surgery
      and at 3, 6, and 12 months after surgery at 5 sites on the distal aspect of the
      M2. RESULTS: The initial mean PD was 5.70 +/- 3.80 mm, with the deepest mean PD
      at the lingual side. At 12 months, a mean PD average of 3.77 +/- 2.86 mm was
      recorded, with a total average recovery of 1.93 +/- 2.46 mm (P < .001), that was
      higher at 3 months (-1.62 mm, P < .001). The PD and attachment level improvements
      were statistically significant (P < .001) and nearly clinically significant from
      baseline to 12-month follow-up and from the buccal to the lingual side of the
      distal aspect of the M2. CONCLUSIONS: Impacted M3s adjacent to M2s lead to
      periodontal defects that are deepest at the lingual side and almost recover at 12
      months after extraction. The first 3 months is considered the cutoff for
      periodontal healing. Young adults with high-risk periodontal M3 impactions may
      benefit from early extraction, which increases spontaneous periodontal healing.

PMID- 22989513
TI  - Therapeutic gene silencing with siRNA for IL-23 but not for IL-17 suppresses the
      development of experimental autoimmune encephalomyelitis in rats.
AB  - Gene silencing with siRNAs is important as a therapeutic tool in autoimmune
      diseases. In this study, we administered siRNAs specific for cytokines that may
      be involved in pathogenesis of experimental autoimmune encephalomyelitis (EAE).
      siRNA specific for IL-23p19 (siRNA-IL-23) suppressed EAE almost completely,
      whereas siRNA-IL-17A did not modulate the clinical course. Flow cytometric
      analysis revealed that siRNA-IL-23 significantly reduced the proportion of both
      IFN-gamma(+)IL-17(-) Th1 and IFN-gamma(-)IL-17(+) Th17 cells in the spinal cord.
      Consistent with this finding, siRNA-IL-23 treatment downregulated IL-12, IL-17
      and IL-23 mRNAs. These findings indicate that IL-23, but not IL-17, play an
      important role in the development of EAE.

PMID- 22989514
TI  - The conserved surface M-protein SiMA of Streptococcus iniae is not effective as a
      cross-protective vaccine against differing capsular serotypes in farmed fish.
AB  - Streptococcus iniae causes invasive infections in fresh and saltwater fish and
      occasional zoonoses. Vaccination against S. iniae is complicated by serotypic
      variation determined by capsular polysaccharide. A potential target for
      serologically cross-protective vaccines is the M-like protein SiMA, an essential
      virulence factor in S. iniae that is highly conserved amongst virulent strains.
      The present study determined how SiMA is regulated and investigated potential as
      a cross-protective vaccine for fish. Electrophoretic mobility shift suggested
      that SiMA is regulated by the multigene regulator Mgx via a binding site in the 
      35 region of the simA promoter. Moreover, expression of simA and mgx was highly
      correlated, with the highest level of simA and mgx expression during exponential
      growth under iron limitation (20-fold increase in relative expression compared to
      growth in Todd-Hewitt broth). Based on these results, a vaccination and challenge
      experiment was conducted in barramundi (Lates calcarifer) to determine whether
      SiMA is protective against S. iniae infection and cross-protective against a
      different capsular serotype. The challenge resulted in 60% mortality in control
      fish. Formalin-killed bacterins prepared from the challenge strain resulted in
      100% protection, whereas bacterins prepared from a serotypically heterologous
      strain resulted in significantly reduced protection, even when culture conditions
      were manipulated to optimise SiMA expression. Moreover, recombinant SiMA protein
      was not protective against the challenge strain in spite of eliciting specific
      antibody response in vaccinated fish. Specific antibody did not increase
      oxidative activity or phagocytosis by barramundi macrophages. Indeed incubating
      S. iniae with antisera significantly reduced phagocytosis. Lack of specific
      antibody mediated opsonisation in spite of 100% protection against challenge with
      the homologous vaccine suggests that other immune parameters result in protection
      of challenged fish.

PMID- 22989515
TI  - Prevalence of Flavobacterium psychrophilum bacterial cells in farmed rainbow
      trout: characterization of metallothionein A and interleukin1-beta genes as
      markers overexpressed in spleen and kidney of diseased fish.
AB  - The aim of the present study was to assess the prevalence of the flavobacteria
      within farmed trout and to quantify their bacterial burden. A total of 61 fish
      were sampled from seven farms, and were distributed in two groups: (1) visibly
      diseased fish suffering from the rainbow trout fry syndrome or the bacterial cold
      water disease caused by the bacteria Flavobacterium psychrophilum and (2)
      normally appearing fish. F. psychrophilum cells were titered by qPCR, targeting a
      specific area of the 16S rRNA gene in skin, muscle, gills, liver, spleen and
      kidney from all fish. The pathogen was detected in these organs whatever the
      health status, with titers ranging from 10(4) to 6 * 10(7)bacteria/g of tissue in
      normally appearing fish, thus showing they were bacterial carriers. Two organs
      allowed differentiation between diseased and normally appearing fish: spleen and
      kidney, with titers ranging from 10(6) to 10(7)bacteria/g of tissue in normally
      appearing fish vs 10(11) to 10(12)bacteria/g of tissue in diseased fish. No
      relationship was found between immunoglobulin M-like titer in plasma and health
      status. Gene expression analysis in fish organs revealed two genes that were
      markers of the bacterial infection: mt-a and il-1beta genes encoding the
      metallothionein A and the interleukin1-beta, respectively. These genes were both
      over-expressed in gills, liver, spleen and kidney of diseased fish. Four genes
      encoding immunity markers were down-regulated in spleen (a key organ implicated
      in immunity) of diseased fish: tgf-beta, cd8-alpha, mhc2-beta and igt, suggesting
      a weakened immune system in diseased fish.

PMID- 22989516
TI  - Carriage of methicillin susceptible and resistant Staphylococcus schleiferi among
      dog with or without topic infections.

PMID- 22989517
TI  - Emergence of the virulence plasmid in Salmonella onarimon and Salmonella blegdam
      from yak.

PMID- 22989518
TI  - MeDIP-HMM: genome-wide identification of distinct DNA methylation states from
      high-density tiling arrays.
AB  - MOTIVATION: Methylation of cytosines in DNA is an important epigenetic mechanism
      involved in transcriptional regulation and preservation of genome integrity in a
      wide range of eukaryotes. Immunoprecipitation of methylated DNA followed by
      hybridization to genomic tiling arrays (MeDIP-chip) is a cost-effective and
      sensitive method for methylome analyses. However, existing bioinformatics methods
      only enable a binary classification into unmethylated and methylated genomic
      regions, which limit biological interpretations. Indeed, DNA methylation levels
      can vary substantially within a given DNA fragment depending on the number and
      degree of methylated cytosines. Therefore, a method for the identification of
      more than two methylation states is highly desirable. RESULTS: Here, we present a
      three-state hidden Markov model (MeDIP-HMM) for analyzing MeDIP-chip data. MeDIP
      HMM uses a higher-order state-transition process improving modeling of spatial
      dependencies between chromosomal regions, allows a simultaneous analysis of
      replicates and enables a differentiation between unmethylated, methylated and
      highly methylated genomic regions. We train MeDIP-HMM using a Bayesian Baum-Welch
      algorithm, integrating prior knowledge on methylation levels. We apply MeDIP-HMM
      to the analysis of the Arabidopsis root methylome and systematically investigate
      the benefit of using higher-order HMMs. Moreover, we also perform an in-depth
      comparison study with existing methods and demonstrate the value of using MeDIP
      HMM by comparisons to current knowledge on the Arabidopsis methylome. We find
      that MeDIP-HMM is a fast and precise method for the analysis of methylome data,
      enabling the identification of distinct DNA methylation levels. Finally, we
      provide evidence for the general applicability of MeDIP-HMM by analyzing promoter
      DNA methylation data obtained for chicken. AVAILABILITY: MeDIP-HMM is available
      as part of the open-source Java library Jstacs (www.jstacs.de/index.php/MeDIP
      HMM). Data files are available from the Jstacs website. CONTACT: seifert@ipk
      gatersleben.de. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 22989519
TI  - [Prognosis factors in donor semen insemination: a 10-years follow-up study of 188
      patients].
AB  - OBJECTIVES: Improving our practice by a constant evaluation is essential in the
      field of donor semen insemination (DI). Our center examined the prognosis factors
      for DI success in order to standardize patient treatment options. PATIENTS AND
      METHODS: We retrospectively analysed all couples referred for DI from January
      2000 till December 2010. RESULTS: We analysed 551 cycles among 188 patients.
      Pregnancy rate by stimulation cycle was 19,8% with birth rate of 16.7%. The rate
      of pregnancy was improved till the fourth trial then plateau. On a patient-based
      analysis, success factors were age (P=0.04), previous successful DSI (P=0.02),
      and no previous failure of an ICSI-C (P=0.035). On a cycle-based analysis,
      success factors were the number of follicles greater than 15mm (P=0.04) and than
      18mm (P=0.001). The percentage of 68.1 patients obtained a child by IVF-D after a
      failed DI. CONCLUSION: There are two predictive factors for DI success: the age
      of the patient and the number of mature follicles. It seems accurate to referred
      patients to IVF-D after four unsuccessful cycles of DSI. This recommendation may
      be adapted according to patient's age and hormonal evaluation.

PMID- 22989520
TI  - Lapatinib and obatoclax kill breast cancer cells through reactive oxygen species
      dependent endoplasmic reticulum stress.
AB  - Previous studies showed that lapatinib and obatoclax interact in a greater-than
      additive fashion to cause cell death and do so through a toxic form of autophagy.
      The present studies sought to extend our analyses. Lapatinib and obatoclax killed
      multiple tumor cell types, and cells lacking phosphatase and tensin homolog
      (PTEN) function were relatively resistant to drug combination lethality;
      expression of PTEN in PTEN-null breast cancer cells restored drug sensitivity.
      Coadministration of lapatinib with obatoclax elicited autophagic cell death that
      was attributable to the actions of mitochondrial reactive oxygen species. Wild
      type cells but not mitochondria-deficient rho-zero cells were radiosensitized by
      lapatinib and obatoclax treatment. Activation of p38 mitogen-activated protein
      kinase (MAPK) and c-Jun NH(2)-terminal kinase 1/2 (JNK1/2) by the drug
      combination was enhanced by radiation, and signaling by p38 MAPK and JNK1/2
      promoted cell killing. In immunohistochemical analyses, the autophagosome protein
      p62 was determined to be associated with protein kinase-like endoplasmic
      reticulum kinase (PERK) and inositol-requiring enzyme 1, as well as with binding
      immunoglobulin protein/78-kDa glucose-regulated protein, in drug combination
      treated cells. Knockdown of PERK suppressed drug-induced autophagy and protected
      tumor cells from the drug combination. Knockdown of PERK suppressed the reduction
      in Mcl-1 expression after drug combination exposure, and overexpression of Mcl-1
      protected cells. Our data indicate that mitochondrial function plays an essential
      role in cell killing by lapatinib and obatoclax, as well as radiosensitization by
      this drug combination.

PMID- 22989521
TI  - Inhibition of autophagy as a strategy to augment radiosensitization by the dual
      phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235.
AB  - We investigated the effect of 2-methyl-2-{4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3
      dihydro-1H-imidazo[4,5-c]quinolin-1-yl]phenyl} propanenitrile (NVP-BEZ235)
      (Novartis, Basel Switzerland), a dual phosphatidylinositol 3-kinase
      (PI3K)/mammalian target of rapamycin (mTOR) inhibitor currently being tested in
      phase I clinical trials, in radiosensitization. NVP-BEZ235 radiosensitized a
      variety of cancer cell lines, including SQ20B head and neck carcinoma cells and
      U251 glioblastoma cells. NVP-BEZ235 also increased in vivo radiation response in
      SQ20B xenografts. Knockdown of Akt1, p110alpha, or mTOR resulted in
      radiosensitization, but not to the same degree as with NVP-BEZ235. NVP-BEZ235
      interfered with DNA damage repair after radiation as measured by the CometAssay
      and resolution of phosphorylated H2A histone family member X foci. NVP-BEZ235
      abrogated the radiation-induced phosphorylation of both DNA-dependent protein
      kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated. Knockdown
      of either p110alpha or mTOR failed to decrease the phosphorylation of DNA-PKcs,
      suggesting that the effect of the drug was direct rather than mediated via
      p110alpha or mTOR. The treatment of cells with NVP-BEZ235 also promoted
      autophagy. To assess the importance of this process in radiosensitization, we
      used the autophagy inhibitors 3-methyladenine and chloroquine and found that
      either drug increased cell killing after NVP-BEZ235 treatment and radiation.
      Knocking down the essential autophagy proteins autophagy related 5 (ATG5) and
      beclin1 increased NVP-BEZ235-mediated radiosensitization. Furthermore, NVP-BEZ235
      radiosensitized autophagy-deficient ATG5(-/-) fibroblasts to a greater extent
      than ATG5(+/+) cells. We conclude that NVP-BEZ235 radiosensitizes cells and
      induces autophagy by apparently distinct mechanisms. Inhibiting autophagy via
      pharmacologic or genetic means increases radiation killing after NVP-BEZ235
      treatment; hence, autophagy seems to be cytoprotective in this situation. Our
      data offer a rationale for combining NVP-BEZ235 along with an autophagy inhibitor
      (i.e., chloroquine) and radiation in future clinical trials.

PMID- 22989523
TI  - Genetic and epigenetic factors in regulation of microRNA in colorectal cancers.
AB  - Studies on miRNA profiling revealed that a large number of them are significantly
      deregulated in human cancers. The molecular mechanisms of this deregulation are
      not totally clarified, even if genetics and epigenetics are frequently involved.
      Single nucleotide polymorphisms (SNPs) are the most common type of genetic
      variation in the human genome. A SNP into miRNA gene might affect the
      transcription of primary miRNA, its processing and miRNA-mRNA interaction. We
      investigated the distribution of sequence variants of miR-146a, miR-196a2, miR
      499 and miR-149 in colorectal cancer (CRC) and their effect on miRNA expression.
      Each variant was identified with HRM. For miR-499 we demonstrated a significant
      reduction of its expression in CRC connected to a specific genotype. To evaluate
      the epigenetic effects on miRNA genes in CRC, we investigated the influence of
      DNA methylation on miR-34b, miR-34c and miR-9-1 expression. We aimed to verify
      the relationship between the methylation status of these miRNA genes and their
      relative expression in tumor samples. For the quantification of DNA methylation
      we adopted a method based on Differential High Resolution Melting (D-HRM).

PMID- 22989522
TI  - Analysis of kalirin-7 knockout mice reveals different effects in female mice.
AB  - Estradiol treatment of ovariectomized rodents is known to affect the morphology
      of dendritic spines and produce behavioral and cognitive effects. Kalirin-7
      (Kal7), a postsynaptic density (PSD)-localized Rho-guanine nucleotide exchange
      factor, is important for dendritic spine formation and stability. Male Kal7
      knockout [Kal7(KO)] mice exhibit a number of abnormal behavioral and biochemical
      phenotypes. Given that chronic 17beta-estradiol (E2) replacement of
      ovariectomized rats enhanced Kal7 expression in the hippocampus and primary
      hippocampal cultures, we assessed the behavioral and biochemical effects of
      chronic E2 treatment of ovariectomized female wild-type and Kal7(KO) mice. Both
      intact and ovariectomized Kal7(KO) female mice exhibited decreased anxiety-like
      behavior compared with the corresponding wild type in the elevated zero maze and
      were unaffected by E2 treatment. Chronic E2 decreased locomotor activity in the
      open field and enhanced performance in a passive-avoidance fear conditioning
      task, which were both unaffected by genotype. Kal7(KO) female mice engaged in
      significantly more object exploration, both familiar and novel, than did wild
      type females. E2 enhanced the acute locomotor response to cocaine, with no
      significant effect of genotype. Similar to Kal7(KO) males, Kal7(KO) females had
      decreased levels of N-methyl-d-aspartate receptor 2B in hippocampal PSD fractions
      with no effect of E2 treatment. The differing behavioral effects of Kal7 ablation
      in female and male mice may offer insight into the molecular underpinnings of
      these differences.

PMID- 22989524
TI  - [Freestyle free perforator flaps for heel reconstruction].
AB  - INTRODUCTION: Heel coverage requires the surgeon to considerate of multiple
      parameters: the type of defect, the exposed tissues, the weight-bearing
      requirements, the donor site morbidity, and the shape of the reconstructed heel
      allowing at best normal footwear. Although many methods of coverage exist, they
      are often chosen at the cost of a compromise between all the parameters
      described. In recent years, perforator freestyle free flaps offer plastic
      surgeons an unparalleled freedom that can adapt the constraints of the
      reconstruction while minimizing the functional and scar donor site morbidity.
      PATIENTS AND METHODS: We present four cases of heel defect of different origins
      treated by three types of tailored perforator freestyle free flaps (ALT, TAP and
      SCIP Flaps). End-to-side anastomosis to the posterior tibial vessels was used in
      three flaps while one flap was anastomosed to the internal plantar artery in an
      end-to-end fashion. RESULTS: No postoperative complication occurred. This
      approach allowed, in all patients, a reconstruction of excellent quality with
      minimal cicatricial morbidity. All patients were walking effectively at 21 days
      postoperatively. CONCLUSION: Perforator freestyle free flaps offer a solution of
      first choice for heel reconstruction. At the price of a linear hidden scar, they
      offer a functional, aesthetic and durable coverage.

PMID- 22989525
TI  - Parental status and gender preferences for children: is differential fertility
      stopping consistent with the trivers-willard hypothesis?
AB  - Based on evolutionary reasoning, Trivers & Willard (1973) predicted status-biased
      sex composition and parental investment with son-preferencing effects in higher,
      and daughter-preferencing effects in lower status groups. Previous research shows
      mixed results. This study uses event-history methods and Swedish register data to
      study one possible mechanism in isolation: do parents in different status groups
      vary in their proclivities to continue fertility based on the sex composition of
      previous offspring? The results show no support for the Trivers-Willard
      hypothesis on a wide range of different status indicators. Future research on the
      stated hypothesis should focus on physiological rather than behavioural
      mechanisms.

PMID- 22989526
TI  - A homozygous splice site mutation in TRAPPC9 causes intellectual disability and
      microcephaly.
AB  - Autosomal recessive intellectual disability is believed to be particularly
      prevalent in highly consanguineous populations and genetic isolates and may
      account for a quarter of all non-syndromic cases. Mutations in more than 50 genes
      have been reported to be involved in autosomal recessive intellectual disability,
      including TRAPPC9 (MIM 611966), mutations of which have been identified in six
      families from different geographical origins. We performed a clinical and
      molecular genetic study of a consanguineous Pakistani family segregating
      intellectual disability and microcephaly. SNP-array-based homozygosity mapping
      revealed suggestive linkage to four genomic regions including one on chromosome 8
      that contained TRAPPC9. We detected a homozygous TRAPPC9 splice donor site
      mutation (c.1024+1G>T) that cosegregated with intellectual disability in the
      family and led to skipping of exon 3 and exons 3 and 4 in blood-derived patient
      RNA. We have thus identified a novel splice site mutation leading to exon
      skipping and premature termination of TRAPPC9 translation. These data further
      suggest that TRAPPC9 mutations -unlike mutations in the vast majority of the
      known intellectual disability-associated genes- constitute a more frequent cause
      of autosomal-recessive cognitive deficits, especially when microcephaly is also
      present.

PMID- 22989527
TI  - Postural influence on the neutral zone of the porcine cervical spine under
      anterior-posterior shear load.
AB  - Segmental instability, characterized by excessive or aberrant movement of the
      vertebrae can be assessed quantitatively using mechanical characteristics within
      a region of minimal resistance called the neutral zone. The diagnosis of
      instability is often used to decide whether or not to surgically fuse the
      vertebrae. Alterations in flexion/extension posture cause changes in both contact
      area and spacing between articulating facets that may lead to changes in the
      mechanical response of the functional spinal unit (FSU) within the neutral zone.
      This investigation quantified neutral zone (NZ) length under anterior and
      posterior shear loading and the influence of posture on the shear NZ
      characteristics of the vertebral joint. Thirty porcine cervical FSUs (15 C34 and
      15 C56) were tested. Endplate area was calculated from measurements of the
      exposed endplates while facet angles were measured from X-rays taken in the
      transverse plane. Specimens were exposed to a 300 N compressive preload followed
      by a test to determine flexion/extension NZ limits. These limits were used as
      target angles during shear passive tests performed in extended and flexed
      postures. Displacement rate during shear passive tests was 0.2mm/s and five
      cycles of anterior-posterior shear were performed to a target of +/-400 N in a
      randomized order of extended, neutral and flexed postures. Shear NZ length and
      average stiffness were quantified. Stiffness within the shear NZ was 67 N/mm in
      the neutral posture. Extended postures produced a 37% (p<0.0001) increase in
      shear stiffness within the NZ compared to both flexed and neutral postures.
      Posture did not influence shear NZ length. Therefore, a true region of zero
      stiffness does not exist during shear loading with a baseline compressive load.
      Neutral zone length for the porcine FSU exposed to shear load was not influenced,
      despite known changes in facet articulation, by changing posture. Average
      stiffness increased likely as a result of increased contact area and force in
      extension. The results from this investigation demonstrate that postural
      deviation of the vertebral joint is not likely a significant confounding factor
      when assessing segmental stability.

PMID- 22989528
TI  - Investigation of metallic and carbon fibre PEEK fracture fixation devices for
      three-part proximal humeral fractures.
AB  - A computational investigation of proximal humeral fracture fixation has been
      conducted. Four devices were selected for the study; a locking plate,
      intramedullary nail (IM Nail), K-wires and a Bilboquet device. A 3D model of a
      humerus was created using a process of thresholding based on the grayscale values
      of a CT scan of an intact humerus. An idealised three part fracture was created
      in addition to removing a standard volume from the humeral head as a
      representation of bone voids that occur as a result of the injury. All finite
      element simulations conducted represent 90 degrees  arm abduction. Simulations
      were conducted to investigate the effect of filling this bone void with calcium
      phosphate cement for each device. The effect of constructing devices from carbon
      fibre polyetheretherketone (CFPEEK) was investigated. Simulations of cement
      reinforced devices predict greater stability for each device. The average
      unreinforced fracture line opening (FLO) is reduced by 48.5% for metallic devices
      with a lesser effect on composite devices with FLO reduced by 23.6%. Relative
      sliding (shear displacement) is also reduced between fracture fragments by an
      average of 58.34%. CFPEEK device simulations predict reduced stresses at the
      device-bone interface.

PMID- 22989530
TI  - Compound instability in dimethyl sulphoxide, case studies with 5-aminopyrimidines
      and the implications for compound storage and screening.
AB  - The oxidation reactions of 5-aminopyrimidine derivatives in dimethyl sulphoxide
      (DMSO) were studied. The DMSO solutions of the studied compounds became deeply
      coloured within a few hours or days. The oxidation products can undergo further
      condensation reactions with the starting pyrimidines to yield bipyrimidines
      and/or pyrimidopteridines. The reaction mechanism of the oxidation-condensation
      reaction was also supported by reactions of the 5-aminopyrimidines with alloxan
      (2,4,5,6-tetraoxopyrimidine). DMSO is often used as the solvent in in vitro tests
      of biological activities, but it is also an oxidising agent and may react with
      solute molecules and significantly affect the quality of the generated
      biochemical data.

PMID- 22989529
TI  - "We don't exist": a qualitative study of marginalization experienced by HIV
      positive lesbian, bisexual, queer and transgender women in Toronto, Canada.
AB  - BACKGROUND: Lesbian, bisexual, queer and transgender (LBQT) women living with HIV
      have been described as invisible and understudied. Yet, social and structural
      contexts of violence and discrimination exacerbate the risk of HIV infection
      among LBQT women. The study objective was to explore challenges in daily life and
      experiences of accessing HIV services among HIV-positive LBQT women in Toronto,
      Canada. METHODS: We used a community-based qualitative approach guided by an
      intersectional theoretical framework. We conducted two focus groups; one focus
      group was conducted with HIV-positive lesbian, bisexual and queer women (n = 7)
      and the second with HIV-positive transgender women (n = 16). Participants were
      recruited using purposive sampling. Focus groups were digitally recorded and
      transcribed verbatim. Thematic analysis was used for analyzing data to enhance
      understanding of factors that influence the wellbeing of HIV-positive LBQT women.
      RESULTS: Participant narratives revealed a trajectory of marginalization.
      Structural factors such as social exclusion and violence elevated the risk for
      HIV infection; this risk was exacerbated by inadequate HIV prevention
      information. Participants described multiple barriers to HIV care and support,
      including pervasive HIV-related stigma, heteronormative assumptions in HIV
      positive women's services and discriminatory and incompetent treatment by health
      professionals. Underrepresentation of LBQT women in HIV research further
      contributed to marginalization and exclusion. Participants expressed a
      willingness to participate in HIV research that would be translated into action.
      CONCLUSIONS: Structural factors elevate HIV risk among LBQT women, limit access
      to HIV prevention and present barriers to HIV care and support. This study's
      conceptualization of a trajectory of marginalization enriches the discussion of
      structural factors implicated in the wellbeing of LBQT women and highlights the
      necessity of addressing LBQT women's needs in HIV prevention, care and research.
      Interventions that address intersecting forms of marginalization (e.g. sexual
      stigma, transphobia, HIV-related stigma) in community and social norms, HIV
      programming and research are required to promote health equity among LBQT women.

PMID- 22989531
TI  - Cytotoxicity and DNA binding property of phenanthrene imidazole with polyglycol
      side chains.
AB  - A series of phenanthrene imidazole with polyglycol side chain (2a-2c and 3a-3c)
      were synthesized and characterized by IR, NMR and MS. The cytotoxicity of 2a-2c
      and 3a-3c against cancer cell lines (HL-60, BGC-823, Bel-7402 and KB) in vitro
      were measured using MTT method. The DNA binding properties of 3a-3c were
      investigated by UV, fluorescence, CD spectroscopies and thermal denaturation. The
      results indicate that 2a exhibits higher cytotoxicity than cisplatin against BGC
      823 and Bel-7402 cell lines, 3b and 3c exhibit higher cytotoxicity than 2b and 2c
      against BGC-823, Bel-7402 and KB cell lines. The cytotoxic effect of 2a-2c
      decrease with the increase of side chains length, the cytotoxic effect of 3a-3c
      increased with the increasing length of side chains against BGC-823, Bel-7402 and
      KB cell lines. Compounds 3a-3c intercalated DNA with a vertical orientation in
      the intercalation pocket. The binding constants of 3a-3c with Ct-DNA are
      1.68*10(6), 1.51*10(6) and 0.709*10(6)M(-1), respectively. The binding affinity
      of 3a-3c with Ct-DNA trended to decrease with the increasing length of polyglycol
      side chains.

PMID- 22989532
TI  - Zizimauritic acids A-C, three novel nortriterpenes from Ziziphus mauritiana.
AB  - Zizimauritic acids A-C (1-3), three novel nortriterpenes with a unique A-nor-E
      seco spiro-lactone ceanothane-type triterpene skeleton, together with 3 known
      triterpenes ceanothenic acid (4), betulinic acid (5), and ceanothic acid (6),
      were isolated from the roots of Ziziphus mauritiana. Compounds 1-4 showed
      cytotoxicities with the IC(50) values ranging from 5.05 to 11.94 MUg/ml, and
      compounds 1 and 3 showed an inhibitory effect on the growth of Staphylococcus
      aureus with the IC(50) values 2.17 and 12.79 MUg/ml. A plausible biosynthetic
      pathway of compounds 1-3 was proposed.

PMID- 22989533
TI  - Discovery of potent inhibitors of receptor protein tyrosine phosphatase sigma
      through the structure-based virtual screening.
AB  - Receptor protein tyrosine phosphatase sigma (PTPsigma) has proved to be a
      promising target for the development of therapeutics for the treatment of
      neurological diseases. Here, we report the first example for a successful
      application of the structure-based virtual screening to identify the novel small
      molecule inhibitors of PTPsigma. These inhibitors revealed high potencies with
      the associated IC(50) values ranging from 0.1 to 1.3 MUM and were also screened
      for having desirable physicochemical properties as a drug candidate. Therefore,
      they deserve consideration for further development by structure-activity
      relationship studies to develop therapeutics for neurological diseases.
      Structural features relevant to the stabilization of the newly identified
      inhibitors in the active site of PTPsigma are discussed in detail.

PMID- 22989534
TI  - Nerve dependence in tissue, organ, and appendage regeneration.
AB  - Many regeneration contexts require the presence of regenerating nerves as a
      transient component of the progenitor cell niche. Here we review nerve
      involvement in regeneration of various structures in vertebrates and
      invertebrates. Nerves are also implicated as persistent determinants in the niche
      of certain stem cells in mammals, as well as in Drosophila. We consider our
      present understanding of the cellular and molecular mechanisms underlying nerve
      dependence, including evidence of critical interactions with glia and non-neural
      cell types. The example of the salamander aneurogenic limb illustrates that
      developmental interactions between the limb bud and its innervation can be
      determinative for adult regeneration. These phenomena provide a different
      perspective on nerve cells to that based on chemical and electrical excitability.

PMID- 22989535
TI  - Liposomal paclitaxel formulations.
AB  - Over the past three decades, taxanes represent one of the most important new
      classes of drugs approved in oncology. Paclitaxel (PTX), the prototype of this
      class, is an anti-cancer drug approved for the treatment of breast and ovarian
      cancer. However, notwithstanding a suitable premedication, present-day
      chemotherapy employing a commercial preparation of PTX (Taxol(r)) is associated
      with serious side effects and hypersensitivity reactions. Liposomes represent
      advanced and versatile delivery systems for drugs. Generally, both in vivo mice
      tumor models and human clinical trials demonstrated that liposomal PTX
      formulations significantly increase a maximum tolerated dose (MTD) of PTX which
      outperform that for Taxol(r). Liposomal PTX formulations are in various stages of
      clinical trials. LEP-ETU (NeoPharm) and EndoTAG(r)-1 (Medigene) have reached the
      phase II of the clinical trials; Lipusu(r) (Luye Pharma Group) has already been
      commercialized. Present achievements in the preparation of various liposomal
      formulations of PTX, the development of targeted liposomal PTX systems and the
      progress in clinical testing of liposomal PTX are discussed in this review
      summarizing about 30 years of liposomal PTX development.

PMID- 22989536
TI  - Role of MRCP in the measurement of the CBD diameter.

PMID- 22989538
TI  - Clinical features in adult patients with in-hospital cardiovascular events with
      confirmed 2009 Influenza A (H1N1) virus infection: comparison with those without
      in-hospital cardiovascular events.
AB  - BACKGROUND: Comprehensive data regarding in-hospital cardiovascular events of
      adults with confirmed 2009 influenza A (H1N1) (2009 H1N1) infections are limited.
      The aim of this study was to determine the clinical characteristics, laboratory
      parameters, and electrocardiographic (ECG) findings for adults with 2009 H1N1
      infections and to assess the differences in these parameters among adult patients
      with and without in-hospital cardiovascular events. METHODS: Seventy-one patients
      were enrolled from the 2009 H1N1 registry database (our hospital registry of
      confirmed 2009 H1N1 infection during the year 2009) and divided according to the
      presence of in-hospital cardiovascular events. Six patients had cardiovascular
      events (CV group) and 65 did not (NCV group). RESULTS: The CV group was more
      likely to be old (p = 0.023). Regarding co-morbidities, underlying coronary heart
      disease (p = 0.001), congestive heart failure (p = 0.001), diabetes (p = 0.001),
      and hypertension (p = 0.014) had significant influences on cardiovascular events.
      The CV group was also more likely to have chest pain (p = 0.034), dyspnea (p =
      0.045), higher leukocyte count (p = 0.014), higher C-reactive protein (p =
      0.010), higher glucose level (p = 0.001), and higher N-terminal probrain
      natriuretic peptide level (p = 0.010) than the NCV group. In addition, the CV
      group had a significantly higher in-hospital mortality rate (p = 0.010) and
      cardiac mortality rate (p = 0.001) than the NCV group. However, there were no
      significant differences in ECG findings between the two groups. CONCLUSION: Our
      study demonstrated that the CV group had higher in-hospital and cardiac mortality
      rates than the NCV group. A meticulous therapeutic approach should be considered
      for elderly patients with 2009 H1N1 infections having coronary heart disease,
      congestive heart failure, diabetes, hypertension, and high levels of leukocyte
      count, hs-CRP, glucose, and NT-proBNP at the time of admission.

PMID- 22989537
TI  - Primary hyperparathyroidism in children and adolescents.
AB  - Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in
      whom the typical presentation is incidentally discovered as asymptomatic
      hypercalcemia. PHPT is much less common in children and adolescents, but has
      greater morbidity in this age group, as most young patients with PHPT will have
      symptomatic hypercalcemia or complications such as kidney stones, abdominal pain,
      and skeletal fragility. An important feature of PHPT in younger patients is the
      relatively high prevalence of germline inactivating mutations of the CASR gene,
      which encodes the calcium-sensing receptor. Biallelic CASR mutations cause
      neonatal severe hyperparathyroidism, a life-threatening condition that presents
      within days of life with marked hypercalcemia, respiratory distress, failure to
      thrive, and skeletal demineralization. By contrast, more common heterozygous CASR
      mutations are generally associated with a benign variant of PHPT termed familial
      hypocalciuric hypercalcemia. Appropriate management of PHPT in children and
      adolescents requires distinction between familial hypocalciuric hypercalcemia,
      which generally requires no specific treatment, and other forms of PHPT that are
      best treated by parathyroidectomy.

PMID- 22989539
TI  - Citrus reticulata peel improves patient tolerance of low-volume polyethylene
      glycol for colonoscopy preparation.
AB  - BACKGROUND: Adequate adjuncts help to reduce the volume of polyethylene glycol
      electrolyte lavage solution (PEG-ELS) needed, to ameliorate patient discomfort,
      and to improve colonic visibility during colonoscopy. This study aimed to assess
      the effect of Citrus reticulata peel (CRP) as an adjunct to low-volume PEG for
      colonic preparation. METHODS: A total of 1092 health examination examinees
      received colonoscopy during the study period. After excluding those who refused
      to participate and those who did not meet our criteria, 212 examinees were
      enrolled into this study. They were divided into the PEG group and the PEG + CRP
      group according to their date of examination. All examinees received 2 L of PEG
      ELS one day before colonoscopy. The PEG + CRP group also received additional CRP
      in the form of a "buccal tablet" between drinks. Tolerance and adverse events
      were assessed by questionnaire, while the quality of bowel preparation for
      colonoscopy was scored by an endoscopist. RESULTS: There were 107 examinees in
      the PEG group and 105 examinees in the PEG + CRP group. The demographic
      characteristics of the examinees were comparable between these two groups.
      Examinees in the PEG + CRP group had a trend of better colonic visibility than
      those in the PEG group (p = 0.056). Moreover, examinees in the PEG + CRP group
      had higher rate of acceptable taste (p = 0.015) and lower rate of difficulty
      swallowing (p = 0.001). The incidences of adverse events including vomiting (p =
      0.045), bloating (p = 0.035), and difficulty sleeping (p < 0.001) were also
      significantly lower in the PEG + CRP group. CONCLUSION: Compared with
      conventional colonic preparation, the application of CRP as an adjunct could
      improve examinees' tolerance, decrease the incidence of adverse events, and
      maintain the quality of colonic cleansing.

PMID- 22989540
TI  - Cranial neurotransmitter alteration in newborn piglets exposed to oxygen.
AB  - BACKGROUND: To evaluate the influence of hyperoxia on neurotransmitters in the
      developing brain of newborn piglets. METHODS: Ten newborn piglets were randomly
      assigned to hyperoxia (inhaled 100% oxygen) or control (inhaled room air) groups
      and ventilated for 4 hours. Blood samples were obtained at 0, 15, 30, and then
      every 30 minutes for 4 hours. Extracts of whole brain tissue were assayed for
      dopamine, serotonin, and their metabolites using high-performance liquid
      chromatography. RESULTS: In comparison with the control group, there was a
      general trend of lower neurotransmitter content in the brains of the hyperoxia
      group. In addition, the levels of dopamine and 3,4-dihydroxyphenylacetic acid in
      the left frontal lobe, and serotonin in the right occipital lobe and left frontal
      lobe, of the hyperoxia group were significantly lower compared with the control
      group (p < 0.05). CONCLUSION: The results indicate that hyperoxia may alter the
      production or metabolism of dopamine and serotonin in some cortical areas of the
      neonatal central nervous system, and it tended to have some inhibitory effects.
      Therefore, pediatricians should be very judicious in using high oxygen on the
      developing brain.

PMID- 22989541
TI  - Immediate results of microsurgical clipping of posterior communicating artery
      aneurysms using the pretemporal transclinoidal approach.
AB  - BACKGROUND: We evaluated adverse ischemic events as early surgical results of
      microsurgical clipping of 44 and 34 posterior communicating artery (PComA)
      aneurysms through the pterional transsylvian and pretemporal transclinoidal
      approach, respectively, between January 2007 and October 2010. METHODS: Patients
      undergoing PComA aneurysm clipping were divided into two groups, and their
      immediate surgical results were compared and analyzed. Those who underwent the
      pterional transsylvian approach (group A) comprised 42 patients with 44 PComA
      aneurysms (24 ruptured and 20 unruptured). Those who underwent the pretemporal
      transclinoidal approach (group B) comprised 32 patients with 34 PComA aneurysms
      (20 ruptured and 14 unruptured). RESULTS: The immediate postoperative total
      occlusion rates were 97.7% in group A and 100% in group B. The pretemporal
      transclinoidal approach significantly reduced the overall risk of silent and
      symptomatic ischemic strokes (p = 0.04) in ruptured PComA clippings and tended to
      lower the incidence of intraoperative aneurysm rupture (p = 0.07) as well as the
      overall ischemic events (p = 0.06) in a total of 78 aneurysm clippings, as
      compared with the pterional transsylvian approach. Although not significantly,
      the pretemporal transclinoidal approach also tended to have a lower incidence of
      intraoperative aneurysm rupture in ruptured aneurysm clippings (p = 0.11), which
      were mainly responsible for the symptomatic ischemia. The pretemporal
      transclinoidal approach had no additional advantage over the traditional
      pterional transsylvian approach in unruptured PComA aneurysm clippings in the
      present study. CONCLUSION: The pretemporal transclinoidal approach achieved
      better visualization of the vital neurovascular structures surrounding PComA
      aneurysms, which might be a key improvement in lowering the risk of
      intraoperative aneurysm rupture and obtaining significantly satisfactory
      immediate surgical results in the microsurgical clipping of PComA aneurysms,
      especially ruptured ones.

PMID- 22989542
TI  - Combined enteral feeding and total parenteral nutritional support improves
      outcome in surgical intensive care unit patients.
AB  - BACKGROUND: For intensive care unit (ICU) patients with gastrointestinal
      dysfunction and in need of total parenteral nutrition (TPN) support, the benefit
      of additional enteral feeding is not clear. This study aimed to investigate
      whether combined TPN with enteral feeding is associated with better outcomes in
      surgical intensive care unit (SICU) patients. METHODS: Clinical data of 88
      patients in SICU were retrospectively collected. Variables used for analysis
      included route and percentage of nutritional support, total caloric intake, age,
      gender, body weight, body mass index, admission diagnosis, surgical procedure,
      Acute Physiology and Chronic Health Evaluation (APACHE) II score, comorbidities,
      length of hospital stay, postoperative complications, blood glucose values and
      hospital mortality. RESULTS: Wound dehiscence and central catheter infection were
      observed more frequently in the group of patients receiving TPN calories less
      than 90% of total calorie intake (p = 0.004 and 0.043, respectively). APACHE II
      scores were higher in nonsurvivors than in survivors (p = 0.001). More
      nonsurvivors received TPN calories exceeding 90% of total calorie intake and were
      in need of dialysis during ICU admission (p = 0.005 and 0.013, respectively).
      Multivariate analysis revealed that the percentage of TPN calories over total
      calories and APACHE II scores were independent predictors of ICU mortality in
      patients receiving supplementary TPN after surgery. CONCLUSION: In SICU patients
      receiving TPN, patients who could be fed enterally more than 10% of total
      calories had better clinical outcomes than patients receiving less than 10% of
      total calorie intake from enteral feeding. Enteral feeding should be given
      whenever possible in severely ill patients.

PMID- 22989543
TI  - Can missed breast cancer be recognized by regular peer auditing on screening
      mammography?
AB  - BACKGROUND: This study was conducted to investigate whether detectable missed
      breast cancers could be distinguished from truly false negative images in a
      mammographic screening by a regular peer auditing. METHODS: Between 2004 and
      2007, a total of 311,193 free nationwide biennial mammographic screenings were
      performed for 50- to 69-year-old women in Taiwan. Retrospectively comparing the
      records in Taiwan's Cancer registry, 1283 cancers were detected (4.1 per 1000).
      Of the total, 176 (0.6 per 1000) initial mammographic negative assessments were
      reported to have cancers (128 traditional films and 48 laser-printed digital
      images). We selected 186 true negative films (138 traditional films and 48 laser
      printed ones) as control group. These were seeded into 4815 films of 2008 images
      to be audited in 2009. Thirty-four auditors interpreted all the films in a single
      blind, randomized, pair-control study. The performance of 34 auditors was
      analyzed by chi-square test. A p value of < 0.05 was considered significant.
      RESULTS: Eight (6 traditional and 2 digital films) of the 176 false negative
      films were not reported by the auditors (missing rate of 4.5%). Of this total, 87
      false negatives were reassessed as positive, while 29 of the 186 true negatives
      were reassessed as positive, making the overall performance of the 34 auditors in
      interpreting the false negatives and true negatives a specificity of 84.4% and
      sensitivity of 51.8%. The specificity and sensitivity in traditional films and
      laser-printed films were 98.6% versus 43.8% and 41.8% versus 78.3%, respectively.
      Almost 42% of the traditional false negative films had positive reassessment by
      the auditors, showing a significant difference from the initial screeners (p <
      0.001). The specificity of their reinterpretation of laser-printed films was
      obviously low. CONCLUSION: Almost 42% of the false negative traditional films
      were judged as missed cancers in this study. A peer auditing should reduce the
      probability of missed cancers.

PMID- 22989544
TI  - Ultrasound-guided compression repair of peripheral artery pseudoaneurysm: 8
      years' experience of a single institute.
AB  - BACKGROUND: Femoral artery pseudoaneurysm is a rare complication but with
      increasing frequency nowadays due to the advances of endovascular intervention.
      Rare cases of brachial or popliteal artery pseudoaneurysms had ever been reported
      and the predictive factors of failed ultrasound-guided compression repair (UGCR)
      are controversial. METHODS: During the past 8 years, 21 patients (12 males and
      nine females; median age, 64 years) with peripheral pseudoaneurysms (femoral
      artery, n = 17; brachial artery, n = 3; popliteal artery, n = 1) were enrolled. A
      high frequency of 10-12 MHz color ultrasound was used to evaluate the presence of
      a pseudoaneurysm. The area of the pseudoaneurysm sac and the width and length of
      the pseudoaneurysm neck were recorded. Under real-time ultrasound guiding,
      gradual pressure was applied with the probe to obliterate flow in the
      pseudoaneurysm neck while still allowing flow through the supplying artery for
      approximately 10-15 minutes with at most three times (45 minutes' compression).
      Follow-up color sonography was obtained at 24 hours to detect any recurrence.
      RESULTS: The mean area and the largest dimension of the 21 pseudoaneurysms were
      7.3 +/- 6.5 cm(2) and 3.6 +/- 1.8 cm, respectively. The mean width and the mean
      length of the pseudoaneurysm neck were 2.1 +/- 0.9 and 3.3 +/- 2.0 mm,
      respectively. Successful thrombosis of the pseudoaneurysm was achieved in
      19(90.5%) patients. The mean compression time of the 19 successful UGCR was 21.2
      +/- 11.0 minutes. Two patients failed the UGCR procedure after a 45-minute
      compression. Both of the two pseudoaneurysms were located in the femoral artery
      with a large width of the pseudoaneurysm neck (4 and 5 mm, respectively).
      CONCLUSION: UGCR is a safe and cost-effective therapy for treating peripheral
      pseudoaneurysms of not only femoral artery, but also brachial artery and
      popliteal artery. We considered the width of the pseudoaneurysm neck to be the
      predictive factor of technical success.

PMID- 22989545
TI  - Endovascular treatment of a nontraumatic left subclavian artery pseudoaneurysm.
AB  - Mycotic subclavian artery pseudoaneurysms are rare. There are controversies over
      the surgical or endovascular approach as the treatment of choice for these
      lesions. The standard surgical debridement might not be a choice for poorly
      surgically reachable lesions or for patients with multiple comorbidities.
      Endovascular aneurysm repair may be an effective alternative in selected cases.
      This treatment was rarely reported previously. Herein, we present a high-surgical
      risk case with a highly suspected left subclavian arterial mycotic
      pseudoaneurysm, which, although difficult to approach surgically, was
      successfully managed with stent grafting and a complete antibiotic treatment
      course. An 89-year-old male was admitted due to intermittent fever and hemoptysis
      for 2 months. Salmonella group B was cultured from his sputum, and a 3.5 cm
      pseudoaneurysm was identified by chest multidetector-row computed tomography
      (MDCT) angiogram. Endovascular treatment with a graft stent was chosen due to
      high surgical risk and difficult surgical access to the lesion. The intervention
      was well planned ad hoc, based on MDCT images and meticulously performed by dual
      endovascular approaches. Antibiotics were continued after the procedure, and the
      patient was discharged from the hospital. As MDCT disclosed near-complete
      regression of the pseudoaneurysms 2 months later and the patient was in healthy
      status, antibiotics were continued for 6 months. He was readmitted 11 months
      later due to lacunar infarction with minor pneumonia over the left lower lung in
      which Salmonella enteritis was also diagnosed. After this acute event, he was
      again hospitalized 14 days later due to sepsis with adult respiratory distress
      syndrome and shortly expired despite all emergent treatment measures. No evidence
      of local subclavian infection recurrence was noted throughout or related to
      subsequent events. In conclusion, endovascular treatment of an infected
      subclavian artery pseudoaneurysm could be a choice in selected patients, but
      treatment of underlying infection determines the clinical outcome.

PMID- 22989546
TI  - Malignant solitary fibrous tumor of the urinary bladder.
AB  - A 67-year-old man was examined for persistent pain over his lower abdomen and was
      found to have a large pelvic tumor. During surgery, we detected a 16 * 9 * 9
      cm(3) urinary bladder tumor with small intestinal adhesions, and performed
      partial cystectomy and segmental resection. Histological and immunohistochemical
      examinations established the diagnosis of malignant solitary fibrous tumor (SFT).
      Only 10 cases of urinary bladder SFT have been reported in the English
      literature; our patient is the second one with malignancy and had a longer follow
      up period than the other case.

PMID- 22989547
TI  - Tumor seeding after diagnostic vitrectomy for choroidal metastasis in breast
      cancer.
AB  - Choroidal metastasis is the most common type of intraocular tumor in adults, and
      in females the most common primary site is the breast. We report a case of
      unilateral choroidal metastasis with exudative retinal detachment as the initial
      presentation of recurrent breast cancer, and subsequent ophthalmic metastasis
      following diagnostic vitrectomy. A 49-year-old woman with a 7-year-history of
      well-treated bilateral breast cancer had been suffering from blurred vision in
      the left eye for 1 week. Ocular examination was normal except for superotemporal
      retinal detachment in the left eye. Neither retinal break nor choroidal mass was
      seen. The patient received scleral buckling and pneumatic retinopexy without
      significant improvement. Fluorescein angiography revealed a suspected choroidal
      metastasis in the left eye, but ocular ultrasonography did not show a visible
      choroidal mass. Two consecutive diagnostic vitrectomies with cytology could not
      confirm malignancy. A systemic workup was also negative. Six months later, two
      tumor masses were noted over two of the sclerotomy wounds of the left eye.
      Pathology showed adenocarcinoma compatible with invasive ductal carcinoma of the
      breast. Ocular metastasis may present as infiltrative choroidal lesions with
      exudative retinal detachment without a visible mass. Invasive procedures, such as
      fine-needle aspiration biopsy and diagnostic vitrectomy, may risk tumor seeding.

PMID- 22989548
TI  - Optimization of TNF-alpha overexpression in Escherichia coli using response
      surface methodology: Purification of the protein and oligomerization studies.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is responsible for many autoimmune
      disorders including rheumatoid arthritis, psoriasis, Chron's disease, stroke, and
      atherosclerosis. Thus, inhibition of TNF-alpha is a major challenge in drug
      discovery. However, a sufficient amount of purified protein is needed for the in
      vitro screening of potential TNF-alpha inhibitors. In this work, induction
      conditions for the production of human TNF-alpha fusion protein in a soluble form
      by recombinant Escherichia coli BL21(DE3) pLysS were optimized using response
      surface methodology based on the central composite design. The induction
      conditions included cell density prior induction (OD(600nm)), post-induction
      temperature, IPTG concentration and post-induction time. Statistical analysis of
      the results revealed that all variables and their interactions had significant
      impact on production of soluble TNF-alpha. An 11% increase of TNF-alpha
      production was achieved after determination of the optimum induction conditions:
      OD(600nm) prior induction 0.55, a post induction temperature of 25 degrees C, an
      IPTG concentration of 1mM and a post-induction time of 4h. We have also studied
      TNF-alpha oligomerization, the major property of this protein, and a K(d) value
      of 0.26nM for protein dimerization was determined. The concentration of where
      protein trimerization occurred was also detected. However, we failed to determine
      a reliable K(d) value for protein trimerization probably due to the
      complexibility of our model.

PMID- 22989550
TI  - Male-mediated infertility in sons of building painters and gardeners: a
      nationwide register-based follow-up study.
AB  - AIM: To investigate whether sons of gardeners and building painters have
      increased risk of infertility in comparison with sons of bricklayers, carpenters
      and electricians. METHODS: Participants were men born 1965-1984 in Denmark whose
      fathers the year before birth had worked as gardeners, painters, bricklayers,
      carpenters or electricians (N=22,978). Cases of infertility were identified by
      Danish registers, and participants were followed-up for up to 24 years after
      their 20th birthday. RESULTS: Sons of gardeners did not have increased risk of
      infertility. Hazard ratios for sons of painters fluctuated around the null in
      main analyses but were 1.6 (98% CI: 1.0-2.5) and 1.7 (95% CI: 0.9-3.2) in the
      subset of participants with smallest risk of paternal exposure misclassification.
      CONCLUSIONS: Working as gardener or building painter was not related to increased
      risk of infertility among the next generation of males in main analyses. However,
      inherent limitations in data may have attenuated true associations.

PMID- 22989549
TI  - Expression of a dominant negative estrogen receptor alpha variant in transgenic
      mice accelerates uterine cancer induced by the potent estrogen
      diethylstilbestrol.
AB  - ERDelta3 transgenic mice expressing a dominant negative estrogen receptor alpha
      (ERalpha) variant lacking the second zinc finger in the DNA binding domain were
      developed to examine its potential to inhibit estrogen action in vivo. To
      investigate if ERDelta3 expression influences uterine carcinogenesis, ERDelta3
      transgenic mice were exposed to diethylstilbestrol (DES) on post-natal days 1-5.
      Neonatal DES treatment induced uterine adenocarcinomas in 81% of 8-month-old
      ERDelta3 mice compared to 49% of wild-type females (p<0.016). ERDelta3 did not
      inhibit the expression of the estrogen-responsive progesterone receptor and
      lactoferrin genes in the presence of ERalpha or modify their expression in
      ERalpha knockout (alphaERKO) mice. Higher circulating 17beta-estradiol levels and
      non-classical signaling by ERDelta3 may be related to the earlier incidence of
      uterine cancer. These findings indicate that expression of this ERalpha variant
      can influence determining events in uterine cancer development and its natural
      occurrence in the human uterus would unlikely be protective.

PMID- 22989551
TI  - Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and
      adult models.
AB  - Electronic cigarettes (EC) and refill fluids are distributed with little
      information on their pre- and postnatal health effects. This study compares the
      cytotoxicity of EC refill fluids using embryonic and adult cells and examines the
      chemical characteristics of refill fluids using HPLC. Refill solutions were
      tested on human embryonic stem cells (hESC), mouse neural stem cells (mNSC), and
      human pulmonary fibroblasts (hPF) using the MTT assay, and NOAELs and IC(50)s
      were determined from dose-response curves. Spectral analysis was performed when
      products of the same flavor had different MTT outcomes. hESC and mNSC were
      generally more sensitive to refill solutions than hPF. All products from one
      company were cytotoxic to hESC and mNSC, but non-cytotoxic to hPF. Cytotoxicity
      was not due to nicotine, but was correlated with the number and concentration of
      chemicals used to flavor fluids. Additional studies are needed to fully assess
      the prenatal effect of refill fluids.

PMID- 22989552
TI  - Two drugs with paradoxical effects on liver regeneration through antiangiogenesis
      and antifibrosis: Losartan and Spironolactone: a pharmacologic dilemma on
      hepatocyte proliferation.
AB  - BACKGROUND: There is a strong relationship between liver regeneration and
      angiogenesis and fibrosis. It is known that Spironolactone, an aldosterone
      antagonist, acting on rennin-aldosterone axis, and Losartan, an angiotensin II
      type I antagonist, have both antifibrotic and antiangiogenic effects.
      Theoretically, the end result of these mechanisms with contradictory influences
      on liver regeneration is not known well. In this study, we aimed to reveal the
      effects on liver regeneration of administration of Spironolactone and Losartan,
      having contradicting effects on regeneration through antiangiogenesis and
      antifibrosis. MATERIALS AND METHODS: A total of 72 Wistar albino rats were
      divided into control, Spironolactone, and Losartan groups and subdivided to
      conduct examinations on days 1, 3, 5, and 7. The specimens were treated with
      proliferating cell nuclear antigen to evaluate the characteristics of liver
      regeneration; with phosphorylated Smad2 (phospho-Smad2), serum transforming
      growth factor beta (TGF-B) 1, and tissue TGF-B1 to evaluate the termination of
      regeneration and with vascular endothelial growth factor receptor 2, Flk-1/KDR,
      to evaluate angiogenesis. RESULTS: The proliferating cell nuclear antigen
      labeling index was found to be significantly higher in Spironolactone and
      Losartan groups than in the control group on days 1, 3, and 5 (P = 0.031, 0.0023,
      and 0.032, respectively). Vascular endothelial growth factor receptor 2, Flk
      1/KDR, expression was significantly lower in Spironolactone and Losartan groups
      than in the control group on days 3, 5, and 7 (P = 0.032, 0.0024, and 0.007,
      respectively). Phospho-Smad2 was significantly lower on days 1, 3, and 5 in
      Spironolactone and Losartan groups than in the control group (P = 0.011, 0.0020,
      and 0.05, respectively). Tissue TGF-B1 levels were significantly lower in
      Spironolactone and Losartan groups than in the control group only on day 3 (P =
      0039). Serum TGF-B1 levels in Losartan groups were significantly different from
      those of control and Spironolactone groups only on day 1 (P < 0.05). CONCLUSIONS:
      Liver regeneration, expected to decrease on day 3, was prolonged and increased
      even on day 5 despite antiangiogenic effects of Losartan and Spironolactone,
      which in fact inhibit fibrosis through phospho-Smad2 and increase regeneration.
      In addition, serum and tissue TGF-B1 levels are not sensitive enough to show
      active TGF-B1 for the evaluation of regeneration.

PMID- 22989553
TI  - When is injury potentially reversible in a lung ischemia-reperfusion model?
AB  - OBJECTIVE: To verify the impact of ischemic time on lung cell viability in an
      experimental model of lung ischemia-reperfusion (IR) injury and its repercussion
      on lung performance after reperfusion. METHODS: Twenty-four animals were
      subjected to selective clamping of the left pulmonary artery and divided into
      four groups (n = 6) according to ischemic time: 15 (IR15), 30 (IR30), 45 (IR45),
      and 60 min (IR60). All animals were observed for 120 min after reperfusion. The
      hemodynamics, arterial blood gases measurements, and histologic changes were
      analyzed. Immunofluorescence assays for caspase 3 and annexin V were performed.
      Lipid peroxidation was assessed by thiobarbituric acid-reactive substances, and
      caspase 3 activity was assessed by colorimetric extract. RESULTS: The partial
      pressure of arterial oxygen significantly decreased at the end of the observation
      period in the IR30, IR45, and IR60 groups (P < 0.05). The final mean arterial
      pressure significantly decreased in the IR60 group (P < 0.05). We observed a
      significant increase in caspase 3 activity and caspase 3-positive cells by
      immunofluorescence in the IR45 group compared with the other groups (P < 0.05).
      Additionally, there was an increase in necrotic cells assessed by annexin V in
      the IR60 group. The histologic score did not show differences among the different
      groups. CONCLUSIONS: The degree of cell damage had a negative impact on lung
      performance. Sixty minutes of lung ischemia and posterior reperfusion resulted in
      an increased number of necrotic cells, suggesting that these cells may not be
      able to reverse the effects of the IR injury because of the lack of viable cells.

PMID- 22989554
TI  - Regulation of mitochondrial function and energetics by reactive nitrogen oxides.
AB  - Endogenous nitric oxide (NO) generated from L-arginine by NO synthase regulates
      mitochondrial function by binding to cytochrome c oxidase in competition with
      oxygen. This interaction can elicit a variety of intracellular signaling events
      of both physiological and pathophysiological significance. Recent lines of
      research demonstrate that inorganic nitrate and nitrite, derived from oxidized NO
      or from the diet, are metabolized in vivo to form NO and other bioactive nitrogen
      oxides with intriguing effects on cellular energetics and cytoprotection. Here we
      discuss the latest advances in our understanding of the roles of nitrate,
      nitrite, and NO in the modulation of mitochondrial function, with a particular
      focus on dietary nitrate and exercise.

PMID- 22989555
TI  - Iatrogenic arteriovenous fistula in the hand: a case report.
AB  - Peripheral intravenous cannulation is widely used in medicine. Arteriovenous
      fistulas are rare complications but their occurrence has never been reported in
      the hands. We report on a young patient who developed a high flow arteriovenous
      fistula on the dorsum of her hand two weeks after a failed peripheral intravenous
      cannulation attempt.

PMID- 22989556
TI  - Body height and socioeconomic status of females at different life stages.
AB  - Adult height reflects long-term nutritional status and exposure to infectious
      diseases, both of which are influenced by socioeconomic factors. Very little
      research has been done on these inequalities from a longitudinal perspective.
      This paper explores the links between body height at different life stages and
      socioeconomic characteristics. Data were obtained from 1008 Polish schoolgirls
      aged 16-18 years for whom earlier data on height were available. The height of
      each subject was measured. Socioeconomic status and age at menarche were assessed
      based on information received from the surveyed girls. Girls' heights in early
      life were ascertained from medical records. All girls were measured by trained
      school nurses at 7, 9 and 14 years of age. Socioeconomic status was found to be
      related to body height, but not to the rate of height gain during childhood and
      adolescence. Girls of a higher socioeconomic status were taller than girls of a
      lower socioeconomic status. On dividing the research material into homogeneous
      groups by maturity status, the same relationship was observed. No significant
      relationships were found between socioeconomic status and rate of height gain
      between ages 7 and 16, 17, 18 years. The findings suggest that socioeconomic
      variation in height is the result of living conditions during the first years of
      life.

PMID- 22989557
TI  - Estimation of genetic effects in multiple cases family studies using penalized
      maximum likelihood methodology.
AB  - Family studies are often used in genetic research to explore associations between
      genetic markers and various phenotypes. A commonly used design oversamples
      families enriched with the disease under study for efficient data collection and
      estimation. For instance, in a multiple cases family study, families are selected
      based on the number of affected relatives. In such cases, valid inference for the
      model parameters relies on the proper modeling of both the within family
      correlations and the outcome-dependent sampling, also known as ascertainment. A
      flexible modeling approach is the ascertainment-corrected mixed-effects model,
      but it is known to only be asymptotically identifiable, because in small samples
      the available data do not provide sufficient information to estimate both the
      intercept and the genetic variance. To deal with this issue, we propose a
      penalized maximum likelihood estimation procedure which reliably estimates the
      model parameters in small family studies by using external population-based
      information.

PMID- 22989558
TI  - Urinary cytokine levels in apparently healthy cats and cats with chronic kidney
      disease.
AB  - Chronic kidney disease (CKD) is a common cause of illness and death in cats. The
      hallmark of CKD in cats is chronic tubulointerstitial nephritis, and inflammation
      contributes to the progression of renal fibrosis. However, at present, it is
      difficult to assess directly the degree of intra-renal inflammation without renal
      biopsy. Measurement of inflammatory cytokine levels in urine may provide a non
      invasive means of assessing intra-renal inflammation. Urine cytokine levels
      (urine cytokine/urine creatinine ratio) were measured in 18 healthy cats and 26
      cats with CKD. When urine cytokine levels in healthy and CKD cats were compared,
      we found significantly higher levels of IL-8 and transforming growth factor-beta1
      (TGF-beta1) in urine of CKD cats, along with significantly lower vascular
      endothelial growth factor (VEGF) levels. A significant positive correlation
      between serum creatinine and TGF-beta1 levels was found in CKD cats. Urinary
      cytokine measurement may, potentially, be a useful means of assessing intra-renal
      inflammation, fibrosis and vascular health in cats with CKD.

PMID- 22989559
TI  - Persistent right aortic arch and associated axial skeletal malformations in cats.
AB  - Persistent right aortic arch (PRAA) in cats is an uncommon vascular anomaly with
      clinical signs referable to oesophageal obstruction. To our knowledge no reports
      of axial skeletal malformations concomitant to PRAA have been reported in cats.
      The aim of this study is to depict a new clinical feature in cats affected by
      PRAA. In the study six cats with a diagnosis of vascular ring anomaly were
      enrolled. A complete physical examination, a neurological examination and a total
      body radiograph were performed on each animal. Four of the six cats showed
      contemporary PRAA and skeletal malformations. Additionally, for the first time, a
      genetic test was performed on one subject to detect DNA alterations in the
      homologous DiGeorge region of cat. The percentage of skeletal malformations
      reported in the normal population was compared with animals with PRAA and showed
      a higher frequency. Genetic testing failed to demonstrate a correlation between
      PRAA and DiGeorge genomic deletion. A review of veterinary and human diseases
      that presented both conditions was assessed. The few animals enrolled do not
      allow definitive conclusions. Further studies are required to corroborate the
      correlation between PRAA and axial skeletal malformations in cats.

PMID- 22989560
TI  - A retrospective study of 180 anaemic cats: features, aetiologies and survival
      data.
AB  - The study comprised 180 anaemic cats. Descriptive and survival data were
      obtained. Cats were classified by aetiology of anaemia development and
      degenerative, anomalous, metabolic, miscellaneous, neoplastic, infectious,
      inflammatory, immune-mediated, toxic, traumatic or vascular disease (DAMNITV)
      classification and anaemia severity. Sixty-four (35.6%) cats had mild [packed
      cell volume (PCV)/haematocrit (HCT) 20-24.9%], 58 (32.2%) moderate (14-19.9%), 23
      (12.8%) severe (11-13.9%) and 35 (19.4%) very severe (<10.9%) anaemia. By
      aetiology of anaemia development, bone marrow (BM) abnormalities were more common
      (95, 52.8%) than haemorrhage (37, 20.6%) or haemolysis (19, 10.6%). By DAMNITV
      classification, infectious diseases were more common (39, 21.7%) than neoplasia
      (36, 20%), metabolic (21, 11.7%), trauma (15, 8.3%), miscellaneous (14, 7.8%),
      inflammatory (11, 6.1%), immune-mediated (11, 6.1%), anomalous (8, 4.4%), toxic
      (2, 1.1%) or vascular disease (1, 0.6%). BM abnormalities were significantly
      associated with more severe anaemia (P = 0.003). Most cats (112, 62.2%) survived
      to discharge whereas 55 (30.6%) were euthanased and 13 (7.2%) died. Survival to
      discharge was not associated with anaemia severity but was associated
      significantly with aetiology of anaemia development (P = 0.046), as cats with
      haemolysis were more likely to survive to discharge than cats with BM
      abnormalities. Survival to discharge was also associated significantly with
      DAMNITV classification (P = 0.010), with cats with neoplasia being less likely,
      and cats with immune-mediated disease more likely, to survive to discharge. Cox
      regression analysis found that survival was not associated with anaemia severity,
      but was associated with DAMNITV classification (P = 0.011) and age (P = 0.082),
      with cats with immune-mediated disease and younger cats more likely to survive.

PMID- 22989561
TI  - Factors associated with the effect of pramipexole on symptoms of idiopathic REM
      sleep behavior disorder.
AB  - BACKGROUND: The clinical effectiveness of pramipexole (PPX), a candidate
      treatment for idiopathic rapid eye movement sleep behavior disorder (iRBD),
      varies among individuals. This study investigates factors associated with PPX
      effectiveness for treating RBD symptoms. METHODS: Ninety-eight consecutive
      patients with RBD who had taken PPX or clonazepam (CNZP) for more than three
      months were enrolled. Factors associated with PPX effectiveness were examined:
      the ratio of REM sleep without atonia to total REM sleep (RWA/REM), length of RBD
      morbidity, frequency of vocalization or abnormal behavior, and Sniffin' Stick
      Test scores. These factors were also compared among the responders to PPX
      monotherapy, CNZP monotherapy, and PPX + CNZP combined therapy. RESULTS: PPX was
      efficacious in 61.7% (50/81) of the subject patients. RWA/REM was associated with
      PPX effectiveness. The cut-off rate of RWA/REM for predicting PPX effectiveness
      was estimated as 16.8%. Responders to PPX + CNZP combined therapy showed
      significantly higher RWA/REM and frequency of vocalization or dream enactment
      behavior than either responders to monotherapy with PPX or to CNZP. CONCLUSION:
      PPX is probably applicable as an alternative to CNZP, especially for mild iRBD
      cases with a lower rate of RWA. Results of this study suggest that dopaminergic
      dysfunction can play a role in iRBD pathophysiology.

PMID- 22989562
TI  - Quantitative XRD analysis of {110} twin density in biotic aragonites.
AB  - {110} Twin densities in biotic aragonite have been estimated quantitatively from
      the peak widths of specific reflections in powder X-ray diffraction (XRD)
      patterns, as well as direct confirmation of the twins using transmission electron
      microscopy (TEM). Influence of the twin density on the peak widths in the XRD
      pattern was simulated using DIFFaX program, regarding (110) twin as
      interstratification of two types of aragonite unit layers with mirrored
      relationship. The simulation suggested that the twin density can be estimated
      from the difference of the peak widths between 111 and 021, or between 221 and
      211 reflections. Biotic aragonite in the crossed-lamellar microstructure (three
      species) and nacreous microstructure (four species) of molluscan shells, fish
      otoliths (two species), and a coral were investigated. The XRD analyses indicated
      that aragonite crystals in the crossed-lamellar microstructure of the three
      species contain high density of the twins, which is consistent with the TEM
      examination. On the other hand, aragonite in the nacre of the four species showed
      almost no difference of the peak widths between the paired reflections,
      indicating low twin densities. The results for the fish otoliths were varied
      between the species. Such variation of the twin density in biotic aragonites may
      reflect different schemes of crystal growth in biomineralization.

PMID- 22989563
TI  - Treatment adherence - room for improvement, not only in autoimmune hepatitis.

PMID- 22989564
TI  - Endothelial progenitor cells in cirrhosis: the more, the merrier?

PMID- 22989566
TI  - Living donor liver transplantation for HCV: will the true outcomes stand up?

PMID- 22989565
TI  - The transcription factor KLF2 mediates hepatic endothelial protection and
      paracrine endothelial-stellate cell deactivation induced by statins.
AB  - BACKGROUND & AIMS: Statins improve hepatic endothelial function and liver
      fibrosis in experimental models of cirrhosis, thus they have been proposed as
      therapeutic options to ameliorate portal hypertension syndrome. The transcription
      factor Kruppel-like factor 2 (KLF2) may be induced by statins in liver sinusoidal
      endothelial cells (SEC), orchestrating an efficient vasoprotective response. The
      present study aimed at characterizing whether KLF2 mediates statins-derived
      hepatic protection. METHODS: Expression of KLF2 and its vasoprotective target
      genes was determined in SEC freshly isolated from control or CCl(4)-cirrhotic
      rats treated with four different statins (atorvastatin, mevastatin, simvastatin,
      and lovastatin), in the presence of mevalonate (or vehicle), under static or
      controlled shear stress conditions. KLF2-derived vasoprotective transcriptional
      programs were analyzed in SEC transfected with siRNA for KLF2 or siRNA-control,
      and incubated with simvastatin. Paracrine effects of SEC highly-expressing KLF2
      on the activation status of rat and human hepatic stellate cells (HSC) were
      evaluated. RESULTS: Statins administration to SEC induced significant
      upregulation of KLF2 expression. KLF2 upregulation was observed after 6h of
      treatment and was accompanied by induction of its vasoprotective programs.
      Simvastatin vasoprotection was inhibited in the presence of mevalonate, and was
      magnified in cells cultured under physiological shear stress conditions. Statin
      dependent induction of vasoprotective genes was not observed when KLF2 expression
      was muted with siRNA. SEC overexpressing KLF2 induced quiescence of HSC through a
      KLF2-nitric oxide-guanylate cyclase-mediated paracrine mechanism. CONCLUSIONS:
      Upregulation of hepatic endothelial KLF2-derived transcriptional programs by
      statins confers vasoprotection and stellate cells deactivation, reinforcing the
      therapeutic potential of these drugs for liver diseases that course with
      endothelial dysfunction.

PMID- 22989567
TI  - Factor VII activating protease (FSAP) exerts anti-inflammatory and anti-fibrotic
      effects in liver fibrosis in mice and men.
AB  - BACKGROUND & AIMS: Factor VII activating protease (FSAP) is a circulating serine
      protease produced in the liver. A single nucleotide polymorphism (G534E, Marburg
      I, MI-SNP) in the gene encoding FSAP (HABP2) leads to lower enzymatic activity
      and is associated with enhanced liver fibrosis in humans. FSAP is activated by
      damaged cells and its substrates include growth factors and hemostasis proteins.
      METHODS: We have investigated the progression of liver fibrosis in FSAP deficient
      mice and FSAP expression in human liver fibrosis. RESULTS: Serum FSAP
      concentrations declined in patients with end-stage liver disease, and hepatic
      FSAP expression was decreased in patients with advanced liver fibrosis and liver
      inflammation. Moreover, there was an inverse correlation between hepatic FSAP
      expression and inflammatory chemokines, chemokine receptors as well as pro
      fibrotic mediators. Upon experimental bile duct ligation, FSAP(-/-) mice showed
      enhanced liver fibrosis in comparison to wild type mice, alongside increased
      expression of alpha-smooth muscle actin, collagen type I and fibronectin that are
      markers of stellate cell activation. Microarray analyses indicated that FSAP
      modulates inflammatory pathways. CONCLUSIONS: Lower FSAP expression is associated
      with enhanced liver fibrosis and inflammation in patients with chronic hepatic
      disorders and murine experimental liver injury. This strengthens the concept that
      FSAP is a "protective factor" in liver fibrosis and explains why carriers of the
      Marburg I SNP have more pronounced liver fibrosis.

PMID- 22989568
TI  - Inhibition of inflammatory CD4 T cell activity by murine liver sinusoidal
      endothelial cells.
AB  - BACKGROUND & AIMS: The liver can mitigate the inflammatory activity of
      infiltrating T cells by mechanisms that are not entirely clear. Here we
      investigated the role of liver sinusoidal endothelial cells (LSECs) in regulating
      the activity of inflammatory CD4 T cells. METHODS: Interactions between T helper
      (Th) 1 or Th17 cells and LSEC were studied by intravital microscopy and by in
      vitro stimulation assays. RESULTS: Circulating CD4 T cells established lasting
      and repeated interactions with liver endothelium in vivo. Stimulation of Th1 and
      Th17 cells by LSEC greatly inhibited their capacity to secrete interferon-gamma
      or interleukin-17 in vitro; in contrast, stimulation by dendritic cells (DCs)
      resulted in considerable secretion of both cytokines. Cytokine release by Th1 or
      Th17 cells seemed to be actively suppressed by LSEC, as indicated by the
      inhibition of cytokine secretion even in the presence of Th1- and Th17-promoting
      DC. This inhibition of CD4 T cell effector function seemed to depend on the
      dominance of inhibitory over activating co-stimulatory signals on LSEC, since (1)
      cytokine secretion could be restored by increased CD28 co-activation; (2) LSEC
      from interleukin-10(-/-) mice, which manifest increased activating signals, such
      as MHC II, and decreased inhibitory signals, such as PD-L1, failed to suppress
      cytokine secretion; and (3) cytokine secretion by Th1 or Th17 cells that lacked
      PD-1, the ligand for inhibitory PD-L1, could not be suppressed by LSEC.
      CONCLUSIONS: LSEC inhibit inflammatory cytokine secretion of Th1 and Th17
      effector CD4 T cells in dependence of interleukin-10 and PD-1.

PMID- 22989569
TI  - Relapse is almost universal after withdrawal of immunosuppressive medication in
      patients with autoimmune hepatitis in remission.
AB  - BACKGROUND & AIMS: Current treatment strategies in autoimmune hepatitis (AIH)
      include long-term treatment with corticosteroids and/or azathioprine. Here we
      determined the risk of relapse after drug withdrawal in patients in long-term
      remission and factors associated with such a relapse. METHODS: A total of 131
      patients (out of a cohort including 844 patients) from 7 academic and 14 regional
      centres in the Netherlands were identified in whom treatment was tapered after at
      least 2 years of clinical and biochemical remission. Relapse was defined as
      alanine-aminotransferase levels (ALT) three times above the upper limit of normal
      and loss of remission as a rising ALT necessitating the reinstitution of drug
      treatment. RESULTS: During follow-up, 61 (47%) patients relapsed and 56 (42%) had
      a loss of remission. In these 117 patients, 60 patients had fully discontinued
      medication whereas 57 patients were still on a withdrawal scheme. One year after
      drug withdrawal, 59% of the patients required retreatment, increasing to 73% and
      81% after 2 and 3 years, respectively. Previous combination therapy of
      corticosteroids and azathioprine, a concomitant autoimmune disease and younger
      age at time of drug withdrawal were associated with an increased risk of relapse.
      Subsequent attempts for discontinuation after initial failure in 32 patients
      inevitably resulted in a new relapse. CONCLUSIONS: This retrospective analysis
      indicates that loss of remission or relapse occurs in virtually all patients with
      AIH in long-term remission when immunosuppressive therapy is discontinued. These
      findings indicate a reluctant attitude towards discontinuation of
      immunosuppressive treatment in AIH patients.

PMID- 22989570
TI  - Recombinant human manganese superoxide dismutase reduces liver fibrosis and
      portal pressure in CCl4-cirrhotic rats.
AB  - BACKGROUND & AIMS: High oxidative stress plays a major role in increasing hepatic
      vascular resistance in cirrhosis, by facilitating liver fibrosis and by
      increasing hepatic vascular tone. This study is aimed at investigating whether
      the use of the novel isoform of recombinant human manganese superoxide dismutase
      (rMnSOD) could be a new therapeutic strategy to reduce oxidative stress and
      portal hypertension in cirrhotic rats. METHODS: In CCl(4)- and BDL-cirrhotic rats
      treated with rMnSOD (i.p. 15 MUg/kg/day) or its vehicle for 7 days, mean arterial
      pressure (MAP), portal pressure (PP) and portal blood flow (PBF) or small
      mesenteric arterial flow (SMABF) were measured. In addition, in CCl(4)-cirrhotic
      rats, we evaluated the hepatic vasodilatory response to acetylcholine, liver
      fibrosis with Sirius red staining and hepatic stellate cell activation by alpha
      smooth muscle actin (alpha-SMA) protein expression. RESULTS: rMnSOD treatment
      significantly reduced PP either in CCl(4)- or BDL-cirrhotic rats without
      significant changes in splanchnic blood flow, suggesting a reduction in hepatic
      vascular resistance. MAP was not modified. Reduction in PP was associated with a
      significant reduction in liver fibrosis, and alpha-SMA protein expression as well
      as with improved vasodilatory response to acetylcholine. CONCLUSIONS: Chronic
      rMnSOD administration to cirrhotic rats reduces portal pressure by reducing
      hepatic vascular resistance without deleterious effects on systemic hemodynamics,
      suggesting that it might constitute a new antioxidant to be considered as
      additional therapy for treating portal hypertension in cirrhosis.

PMID- 22989571
TI  - Hepatitis B virus DNA integration in tumour tissue of a non-cirrhotic HFE
      haemochromatosis patient with hepatocellular carcinoma.
AB  - Co-existence of multiple causes of liver injury increases the risk of
      hepatocellular carcinoma (HCC) development. HCC usually develops in patients with
      cirrhosis although it may also occur in individuals with no or mild liver
      disease, in particular in cases with hepatitis B virus (HBV) infection. Here we
      report the case of a 43year-old man with HFE-haemochromatosis, seronegative for
      hepatitis B and C infections, who developed HCC in the absence of severe liver
      damage. Both tumoural and non-tumoural liver DNA extracts were tested by nested
      PCR and primers specific for four different HBV genomic regions in order to
      evaluate the presence of occult HBV infection. Only X gene sequences were
      detected in tumour (but not in non-tumour) DNA extracts. HBV-Alu PCR showed a HBV
      integration involving a 5'-deleted X gene with an intact enhancer-II/basal-core
      promoter region. The viral-host junction sequencing revealed that this integrant
      was located upstream of the partitioning-defective-6-homolog-gamma gene (PARD6G)
      and real time-PCR quantification demonstrated that PARD6G was overexpressed in
      tumour compared to non-tumour liver tissues. In conclusion, the combination of
      HFE-haemochromatosis and occult HBV infection in this patient might have led to a
      sequel of cellular events that determined the development of HCC even in the
      absence of cirrhosis.

PMID- 22989572
TI  - Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: a large
      multicenter AGEO study.
AB  - BACKGROUND & AIMS: The current standard treatment for advanced hepatocellular
      carcinoma (HCC) is sorafenib. This drug is effective but generally does not
      induce tumor shrinkage and other treatment options are still needed. METHODS:
      This retrospective multicenter study included all consecutive patients with
      advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and
      2010. Survival curves were drawn with the Kaplan-Meier method and compared with
      the log-rank test. Univariate and multivariate analyses were used to evaluate
      prognostic factors. RESULTS: Two hundred four consecutive patients were treated
      with GEMOX (median age, 60 years; men, 86%; underlying cirrhosis, 76%). Grade 3-4
      toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia
      18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16%
      of the cases. The overall response and disease control rates were 22% (95% CI, 16
      27) and 66% (95% CI, 59-72), respectively. No clinical or biological factors were
      associated with the treatment response, and 8.5% of the patients were
      subsequently eligible for curative-intent therapies after downstaging. Median
      PFS, TTP, and OS were 4.5 (95% CI, 4-6), 8 (95% CI, 6-11), and 11 months (95% CI,
      9-14), respectively. In multivariate analysis, gender (p=0.03), underlying
      cirrhosis (p=0.01), CLIP score (p=0.03), and response to GEMOX (p<0.0001) were
      independently associated with OS. CONCLUSIONS: This large study confirms that
      GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor
      responses permitted potentially curative treatment that was not initially
      feasible in a significant proportion of patients.

PMID- 22989573
TI  - LEFT ventricular function assessed by echocardiography in cirrhosis: relationship
      to systemic hemodynamics and renal dysfunction.
AB  - BACKGROUND & AIMS: The current study aimed at assessing the potential role of
      cardiac abnormalities in the pathogenesis of circulatory and renal dysfunction in
      cirrhosis. METHODS: One hundred and fifty-two patients (34 without ascites, 95
      with ascites without renal failure and 21 with hepatorenal syndrome) were
      evaluated using Doppler echocardiography. In 102 patients, diastolic function was
      assessed by measuring parameters related to ventricular filling velocity, mitral
      annulus velocity and left atrial dimensions. Cardiopulmonary pressures were also
      measured by cardiac catheterization in 54 patients. In 50 additional patients,
      left ventricular myocardial strain was performed to estimate myocardial
      contractility and systolic function. RESULTS: Grade 1 and 2 diastolic dysfunction
      was present in 41% and 16% of the patients, respectively. There was no patient
      with severe grade 3 diastolic dysfunction. Grade 2 diastolic dysfunction was
      associated with higher cardiopulmonary pressures but values were within the
      normal limits in all cases. Diastolic dysfunction directly correlated with liver
      failure but not with the degree of impairment in circulatory and renal function.
      The proportion of patients without or with grade 1 or 2 diastolic dysfunction was
      similar in patients with compensated cirrhosis, with ascites without renal
      failure or with hepatorenal syndrome despite marked differences in the degree of
      circulatory dysfunction, as indicated by plasma renin activity and noradrenaline
      concentration. The heart rate and systolic function were normal in all cases.
      There were no differences between patients without ascites, with ascites without
      renal failure or with HRS, despite marked differences in the activity of the
      renin-angiotensin system and sympathetic nervous system. These features indicate
      an impaired response of cardiac chronotropic and inotropic function to changes in
      systemic hemodynamics. CONCLUSIONS: These data indicates that: (1) diastolic
      dysfunction is frequent in cirrhosis but in most cases it is of mild degree and
      does not increase the cardiopulmonary pressure to abnormal levels. This feature,
      which may be due to the central hypovolemia of cirrhosis, probably accounts for
      the lack of symptoms associated with this condition. (2) Diastolic dysfunction in
      cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. (3) In
      cirrhosis, there is a lack of response of the left ventricular systolic and
      chronotropic function to peripheral arterial vasodilation and activation of the
      sympathetic nervous system and this feature is an important contributory factor
      to the progression of circulatory dysfunction and the pathogenesis of ascites and
      HRS.

PMID- 22989575
TI  - Patterns and predictors of participation in leisure activities outside of school
      in children and adolescents with Cerebral Palsy.
AB  - This study analyzed the patterns and predictors of participation in leisure
      activities outside of school of Spanish children and adolescents with Cerebral
      Palsy (CP). Children and adolescents with CP (n = 199; 113 males and 86 females)
      participated in this cross-sectional study. Their mean age was 12.11 years (SD =
      3.02; range 8-18 years), and they were evaluated using the Spanish version of the
      Children's Assessment of Participation and Enjoyment (CAPE). Means, standard
      deviations and percentages were used to characterize the profile of
      participation, and linear regression analyses were employed to assess
      associations between the variables (child, family and environmental factors) and
      the diversity, intensity and enjoyment of participation. Children and adolescents
      with CP reported low diversity and intensity of participation and high levels of
      enjoyment. Participation in leisure activities outside of school was determined
      more by child and environmental factors than by family ones.

PMID- 22989576
TI  - A systematic review of mindfulness intervention for individuals with
      developmental disabilities: long-term practice and long lasting effects.
AB  - Can individuals with developmental disabilities learn mindfulness? If so, with
      what result? A systematic literature review identified 12 studies that taught
      mindfulness practice to individuals with mild to severe developmental
      disabilities, demonstrating that mindfulness intervention could significantly
      reduce the behavioural and/or psychological problems of this population. The
      majority of these mindfulness intervention studies were longitudinal, featuring
      long intervention periods and long lasting intervention effects. This paper
      analyses the characteristics and objectives of mindfulness interventions, along
      with their effects, focusing on the adjustments made to intervention content and
      instruction strategies to meet the specific requirements of individuals with
      developmental disabilities. The potential for improving mindfulness interventions
      for people with developmental disabilities is also discussed.

PMID- 22989577
TI  - Description and psychometric properties of the CP QOL-Teen: a quality of life
      questionnaire for adolescents with cerebral palsy.
AB  - To assess the measurement properties of a new QOL instrument, the Cerebral Palsy
      Quality of Life Questionnaire-Teen (CP QOL-Teen), in adolescents with cerebral
      palsy (CP) aged 13-18 years, examining domain structure, reliability, validity
      and adolescent-caregiver concordance. Based on age, 695 eligible families were
      invited to participate by mail. Questionnaires were returned by 112 primary
      caregivers (71.8% of questionnaires sent). 87 adolescents aged 12-18 years also
      completed the questionnaires. CP QOL-Teen, generic QOL instruments (KIDSCREEN,
      Pediatric Quality of Life Inventory), functioning (Gross Motor Function
      Classification System) and a condition-specific instrument (PedsQL-CP) were used.
      Principal components analysis produced seven scales: wellbeing and participation;
      communication and physical health; school wellbeing; social wellbeing; access to
      services; family health; feelings about functioning. Cronbach's alphas for the
      derived scales ranged from 0.81 to 0.96 (primary caregiver report) and 0.78 to
      0.95 (adolescent report). Test-retest reliability (4 weeks) ranged from 0.57 to
      0.88 for adolescent self-report and 0.29 to 0.83 for primary caregiver report.
      Moderate correlations were observed with other generic and condition specific
      measures of QOL, indicating adequate construct validity. Moderate correlations
      were observed between adolescent self-report and primary caregiver proxy report.
      This study demonstrates acceptable psychometric properties of both the adolescent
      self-report and the primary caregiver proxy report versions of the CP QOL-Teen.

PMID- 22989574
TI  - Crizotinib for the treatment of ALK-rearranged non-small cell lung cancer: a
      success story to usher in the second decade of molecular targeted therapy in
      oncology.
AB  - Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U.S. Food and Drug
      Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged
      non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first
      publication of ALK-rearranged NSCLC. The crizotinib approval was accompanied by
      the simultaneous approval of an ALK companion diagnostic fluorescent in situ
      hybridization assay for the detection of ALK-rearranged NSCLC. Crizotinib
      continued to be developed as an ALK and MET inhibitor in other tumor types driven
      by alteration in ALK and MET. Crizotinib has recently been shown to be an
      effective ROS1 inhibitor in ROS1-rearranged NSCLC, with potential future clinical
      applications in ROS1-rearranged tumors. Here we summarize the heterogeneity
      within the ALK- and ROS1-rearranged molecular subtypes of NSCLC. We review the
      past and future clinical development of crizotinib for ALK-rearranged NSCLC and
      the diagnostic assays to detect ALK-rearranged NSCLC. We highlight how the
      success of crizotinib has changed the paradigm of future drug development for
      targeted therapies by targeting a molecular-defined subtype of NSCLC despite its
      rarity and affected the practice of personalized medicine in oncology,
      emphasizing close collaboration between clinical oncologists, pathologists, and
      translational scientists.

PMID- 22989578
TI  - Dorsal area 46 is a major target of disynaptic projections from the medial
      temporal lobe.
AB  - The medial temporal lobe (MTL) is responsible for various mnemonic functions,
      such as association/conjunction memory. The lateral prefrontal cortex (LPFC) also
      plays crucial roles in mnemonic functions and memory-based cognitive behaviors,
      for example, decision-making. Therefore, it is considered that the MTL and LPFC
      connect with each other and cooperate for the control of cognitive behaviors.
      However, there exist very weak, if any, direct inputs from the MTL to the LPFC.
      Employing retrograde transsynaptic transport of rabies virus, we investigated the
      organization of disynaptic bottom-up pathways connecting the MTL and the
      inferotemporal cortex to the LPFC in macaques. Three days after rabies injections
      into dorsal area 46, a large number of labeled neurons were observed in the MTL,
      such as the hippocampal formation (including the entorhinal cortex), the
      perirhinal cortex, and the parahippocampal cortex. In contrast, a majority of the
      labeled neurons were located in the inferotemporal cortex following rabies
      injections into ventral area 46 and lateral area 12. Rabies injections into
      lateral area 9/area 8B labeled only a small number of neurons in the MTL and the
      inferotemporal cortex. The present results indicate that, among the LPFC, dorsal
      area 46 is the main target of disynaptic inputs from the MTL. 

PMID- 22989579
TI  - Coding of melodic gestalt in human auditory cortex.
AB  - The perception of a melody is invariant to the absolute properties of its
      constituting notes, but depends on the relation between them-the melody's
      relative pitch profile. In fact, a melody's "Gestalt" is recognized regardless of
      the instrument or key used to play it. Pitch processing in general is assumed to
      occur at the level of the auditory cortex. However, it is unknown whether early
      auditory regions are able to encode pitch sequences integrated over time (i.e.,
      melodies) and whether the resulting representations are invariant to specific
      keys. Here, we presented participants different melodies composed of the same 4
      harmonic pitches during functional magnetic resonance imaging recordings.
      Additionally, we played the same melodies transposed in different keys and on
      different instruments. We found that melodies were invariantly represented by
      their blood oxygen level-dependent activation patterns in primary and secondary
      auditory cortices across instruments, and also across keys. Our findings extend
      common hierarchical models of auditory processing by showing that melodies are
      encoded independent of absolute pitch and based on their relative pitch profile
      as early as the primary auditory cortex. 

PMID- 22989580
TI  - Inter- and intrahemispheric dissociations in ideomotor apraxia: a large-scale
      lesion-symptom mapping study in subacute brain-damaged patients.
AB  - Pantomimes of object use require accurate representations of movements and a
      selection of the most task-relevant gestures. Prominent models of praxis,
      corroborated by functional neuroimaging studies, predict a critical role for left
      parietal cortices in pantomime and advance that these areas store representations
      of tool use. In contrast, lesion data points to the involvement of left inferior
      frontal areas, suggesting that defective selection of movement features is the
      cause of pantomime errors. We conducted a large-scale voxel-based lesion-symptom
      mapping analyses with configural/spatial (CS) and body-part-as-object (BPO)
      pantomime errors of 150 left and right brain-damaged patients. Our results
      confirm the left hemisphere dominance in pantomime. Both types of error were
      associated with damage to left inferior frontal regions in tumor and stroke
      patients. While CS pantomime errors were associated with left temporoparietal
      lesions in both stroke and tumor patients, these errors appeared less associated
      with parietal areas in stroke than in tumor patients and less associated with
      temporal in tumor than stroke patients. BPO errors were associated with left
      inferior frontal lesions in both tumor and stroke patients. Collectively, our
      results reveal a left intrahemispheric dissociation for various aspects of
      pantomime, but with an unspecific role for inferior frontal regions. 

PMID- 22989581
TI  - Functional regeneration of the ex-vivo reconstructed mesocorticolimbic
      dopaminergic system.
AB  - CNS reparative-medicine therapeutic strategies need answers on the putative
      recapitulation of the basic rules leading to mammalian CNS development. To
      achieve this aim, we focus on the regeneration of functional connections in the
      mesocorticolimbic dopaminergic system. We used organotypic slice cocultures of
      ventral tegmental area/substantia nigra (VTA/SN) and prefrontal cortex (PFC) on a
      multielectrode array (MEA) platform to record spikes and local field potentials.
      The spontaneously growing synaptically based bidirectional bursting activity was
      followed from 2 to 28 days in vitro (DIV). A statistical analysis of excitatory
      and inhibitory neurons properties of the physiological firing activity
      demonstrated a remarkable, exponentially increasing maturation with a time
      constant of about 5-7 DIV. Immunohistochemistry demonstrated that the ratio of
      excitatory/inhibitory neurons (3:1) was in line with the functional results
      obtained. Exemplary pharmacology suggested that GABAA receptors were able to
      exert phasic and tonic inhibition typical of an adulthood network. Moreover,
      dopamine D2 receptor inactivation was equally inhibitory both on the spontaneous
      neuronal activity recorded by MEA and on patch-clamp electrophysiology in PFC
      pyramidal neurons. These results demonstrate that axon growth cones reach
      synaptic targets up to full functionality and that organotypic cocultures of the
      VTA/SN-PFC perfectly model their newly born dopaminergic, glutamatergic and
      GABAergic neuronal circuitries. 

PMID- 22989582
TI  - A hierarchical structure of cortical interneuron electrical diversity revealed by
      automated statistical analysis.
AB  - Although the diversity of cortical interneuron electrical properties is well
      recognized, the number of distinct electrical types (e-types) is still a matter
      of debate. Recently, descriptions of interneuron variability were standardized by
      multiple laboratories on the basis of a subjective classification scheme as set
      out by the Petilla convention (Petilla Interneuron Nomenclature Group, PING).
      Here, we present a quantitative, statistical analysis of a database of nearly
      five hundred neurons manually annotated according to the PING nomenclature. For
      each cell, 38 features were extracted from responses to suprathreshold current
      stimuli and statistically analyzed to examine whether cortical interneurons
      subdivide into e-types. We showed that the partitioning into different e-types is
      indeed the major component of data variability. The analysis suggests refining
      the PING e-type classification to be hierarchical, whereby most variability is
      first captured within a coarse subpartition, and then subsequently divided into
      finer subpartitions. The coarse partition matches the well-known partitioning of
      interneurons into fast spiking and adapting cells. Finer subpartitions match the
      burst, continuous, and delayed subtypes. Additionally, our analysis enabled the
      ranking of features according to their ability to differentiate among e-types. We
      showed that our quantitative e-type assignment is more than 90% accurate and
      manages to catch several human errors. 

PMID- 22989583
TI  - Synchronization across sensory cortical areas by electrical microstimulation is
      sufficient for behavioral discrimination.
AB  - The temporal correlation hypothesis proposes that cortical neurons engage in
      synchronized activity, thus configuring a general mechanism to account for a
      range of cognitive processes from perceptual binding to consciousness. However,
      most studies supporting this hypothesis have only provided correlational, but not
      causal evidence. Here, we used electrical microstimulation of the visual and
      somatosensory cortices of the rat in both hemispheres, to test whether rats could
      discriminate synchronous versus asynchronous patterns of stimulation applied to
      the same cortical sites. To disambiguate synchrony from other related parameters,
      our experiments independently manipulated the rate and intensity of stimulation,
      the spatial locations of stimulation, the exact temporal sequence of stimulation
      patterns, and the degree of synchrony across stimulation sites. We found that
      rats reliably distinguished between 2 microstimulation patterns, differing in the
      spatial arrangement of cortical sites stimulated synchronously. Also, their
      performance was proportional to the level of synchrony in the microstimulation
      patterns. We demonstrated that rats can recognize artificial current patterns
      containing precise synchronization features, thus providing the first direct
      evidence that artificial synchronous activity can guide behavior. Such precise
      temporal information can be used as feedback signals in machine interface
      arrangements. 

PMID- 22989585
TI  - Decreased NOS1 expression in the anterior cingulate cortex in depression.
AB  - Decreased function of the anterior cingulate cortex (ACC) is crucially involved
      in the pathogenesis of depression. A key role of nitric oxide (NO) has also been
      proposed. We aimed to determine the NO content in the cerebrospinal fluid (CSF)
      and the expression of NO synthase (NOS) isoforms, that is, NOS1, NOS2, and NOS3
      in the ACC in depression. In depressive patients, CSF-NOx levels (the levels of
      the NO metabolites nitrite and nitrate) were significantly decreased (P = 0.007),
      indicating a more general decrease of NO production in this disorder. This agreed
      with a trend toward lower NOS1-mRNA levels (P = 0.083) and a significant decrease
      of NOS1-immunoreactivity (ir) (P = 0.043) in ACC. In controls, there was a
      significant positive correlation between ACC-NOS1-ir cell densities and their CSF
      NOx levels. Furthermore, both localization of NOS1 in pyramidal neurons that are
      known to be glutamatergic and co-localization between NOS1 and GABAergic neurons
      were observed in human ACC. The diminished ACC-NOS1 expression and decreased CSF
      NOx levels may be involved in the alterations of ACC activity in depression,
      possibly by affecting glutamatergic and GABAergic neurotransmission. 

PMID- 22989584
TI  - Quantification and discrimination of abnormal sulcal patterns in polymicrogyria.
AB  - Polymicrogyria (PMG) is a malformation of cortical development characterized by
      an irregular gyral pattern and its diagnosis and severity have been qualitatively
      judged by visual inspection of imaging features. We aimed to provide a
      quantitative description of abnormal sulcal patterns for individual PMG brains
      using our sulcal graph-based analysis and examined the association with language
      impairment. The sulcal graphs were constructed from magnetic resonance images in
      26 typical developing and 18 PMG subjects and the similarity between sulcal
      graphs was computed by using their geometric and topological features. The
      similarities between typical and PMG groups were significantly lower than the
      similarities measured within the typical group. Furthermore, more lobar regions
      were determined to be abnormal in most patients when compared with the visual
      diagnosis of PMG involvement, suggesting that PMG may have more global effects on
      cortical folding than previously expected. Among the PMG, the group with intact
      language development showed sulcal patterns more closely matched with the typical
      than the impaired group in the left parietal lobe. Our approach shows the
      potential to provide a quantitative means for detecting the severity and extent
      of involvement of cortical malformation and a greater understanding of genotype
      phenotype and clinical-imaging features correlations. 

PMID- 22989586
TI  - Interdisciplinary rounds in the postanesthesia care unit: a new perioperative
      paradigm.
AB  - Patients in the perioperative and postanesthesia care unit (PACU) experience
      several transitions in patient care at the same time that the majority of major
      morbidities will arise. The transitions for these patients are at the critical
      juncture between surgery and a steady sustained recovery. Historically these
      important medical problems have been addressed as a nonformalized process. The
      authors have introduced a formalized process, based on interdisciplinary rounding
      strategies used in intensive care units, to attend patients and address problems.

PMID- 22989587
TI  - Postoperative considerations of neuraxial anesthesia.
AB  - Spinal and epidural anesthesia and analgesia, and the combination of the two
      techniques, have been excellent choices for the management of certain surgical
      procedures and continue to grow in popularity. The demand for increased patient
      mobility and quicker discharge for both inpatients and outpatients lends itself
      to the benefits of regional anesthesia. A neuraxial block is indicated for any
      surgical procedure in which the appropriate sensory level can be accomplished
      without any adverse outcome. This article outlines the indications and
      contraindications for these techniques.

PMID- 22989588
TI  - Perioperative glycemic control.
AB  - Perioperative hyperglycemia has potential significant adverse consequences of
      increased mortality and morbidity including surgical site infection, renal
      insufficiency and anemia requiring transfusion. Both diabetic and non-diabetic
      patients are affected adversely by perioperative hyperglycemia. However, these
      two subgroups do not necessarily benefit equally from perioperative glycemic
      control. Moreover, ideal target glucose range as well as the appropriate patient
      population(s) for whom glycemic control offers the most benefit have yet to be
      fully elucidated. However, there are clear potential adverse consequences of
      tight control such as hypoglycemia.

PMID- 22989589
TI  - Anxiolytic use in the postoperative care unit.
AB  - Postoperative anxiety has received less attention historically than preoperative
      anxiety. Recognition that anxiety occurs throughout the perioperative period has
      led to increased interest in identifying and treating anxiety in the
      postoperative period. This article outlines the causes of postoperative anxiety,
      how it is classified, the effects of anxiety on outcomes after surgery, and some
      of the clinical procedures that produce the highest levels of anxiety for
      patients. In addition, an attempt is made to delineate the major risk factors for
      developing postoperative anxiety and the classic therapeutic modalities used to
      reduce symptoms and treat the psychological manifestations of anxiety.

PMID- 22989590
TI  - Management of postoperative nausea and vomiting: how to deal with refractory
      PONV.
AB  - Postoperative nausea and vomiting (PONV) constitutes a significant factor in
      delaying recovery after anesthesia and impairing patient satisfaction. To date
      the prevention of PONV using single or multimodal interventions, usually based on
      risk assessment, has gained some popularity. However, comprehensive
      implementation and knowledge transfer of the latest accomplishments in the
      prevention of PONV is only slowly being adopted into clinical practice.
      Preventing PONV is the first step in avoiding refractory PONV. This review
      comments mainly on the management of refractory PONV. As the data on coping with
      established PONV are rare, further studies focusing on treatment of established
      PONV are needed.

PMID- 22989591
TI  - Postoperative noninvasive ventilation.
AB  - General anesthesia and surgery are associated with changes in the shape of the
      chest that result in atelectasis, a major factor in the development of
      postoperative respiratory failure. Postoperative noninvasive positive pressure
      ventilation (NIPPV) has been shown to improve oxygenation and ventilation for
      high-risk patients. NIPPV has been used as rescue therapy for patients developing
      acute respiratory distress postoperatively, and appears to be most frequently
      successful in patients whose problem is atelectasis or obesity. Failure to
      respond to NIPPV after 20 minutes is usually an indication of intubation,
      mechanical ventilation, and transfer to the intensive care unit.

PMID- 22989593
TI  - Hemodynamic and related challenges: monitoring and regulation in the
      postoperative period.
AB  - The clinician caring for patients in the immediate postoperative period must
      maintain a high index of suspicion for the development of complications. Evolving
      illness manifests itself throughout the continuum of care and must be recognized
      and aggressively managed to ensure optimal outcome. This article discusses common
      hemodynamic problems encountered in the postanesthesia care unit. These problems
      are presented in a clinical framework that is familiar to experienced
      practitioners and recognizable to trainees. This article reviews of these common
      problems including relevant physiologic principles; effects on hemodynamics; and
      a logical approach to evaluation, monitoring, and management of a complex
      postoperative patient.

PMID- 22989592
TI  - Decreased urine output and acute kidney injury in the postanesthesia care unit.
AB  - Decreased urine output and acute kidney injury (also known as acute renal
      failure) are among the most important complications that may develop in the
      postanesthetic period. In this article, the authors present definitions of
      decreased urine output, oliguria, and acute kidney injury. They review the
      epidemiology, pathophysiology, and prevention of postoperative acute kidney
      injury. Finally, the article offers approaches to diagnosis and management of the
      postsurgical patient with decreased urine output or acute kidney injury.

PMID- 22989594
TI  - Perioperative quality and improvement.
AB  - Health care quality and safety are becoming more transparent, and consumers will
      increasingly value safety and quality rating in choosing where they go for
      surgery. Perioperative services are major drivers to a hospital's safety rating.
      Surgical services are often the most, or one of the most, profitable services,
      and loss of referrals and poor media reports will directly reduce margins. This
      article aims to guide leaders and perioperative staff in how to start improving
      perioperative quality and safety in health care and surgical services.

PMID- 22989595
TI  - The Post Anesthesia Care Unit (PACU). Foreword.

PMID- 22989596
TI  - Postoperative care.

PMID- 22989597
TI  - 25C-NBOMe--new potent hallucinogenic substance identified on the drug market.
AB  - This publication reports analytical properties of a new hallucinogenic substance
      identified in blotter papers seized from the drug market, namely 25C-NBOMe [2-(4
      chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine]. The identification
      was based on results of comprehensive study including several analytical methods,
      i.e., GC-EI-MS (without derivatization and after derivatization with TFAA), LC
      ESI-QTOF-MS, FTIR and NMR. The GC-MS spectrum of 25C-NBOMe was similar to those
      obtained for other representatives of the 25-NBOMe series, with dominant ions
      observed at m/z=150, 121 and 91. Fragment ions analogic to those in 2C-C (4
      chloro-2,5-dimethoxy-beta-phenylethanamine) were also observed, but their
      intensities were low. Derivatization allowed the determination of molecular mass
      of the investigated substance. The exact molecular mass and chemical formula were
      confirmed by LC-QTOF-MS experiments and fragmentation pattern under electrospray
      ionization was determined. The MS/MS experiments confirmed that the investigated
      substance was N-(2-methoxy)benzyl derivative of 2C-C. The substance was also
      characterized by FTIR spectroscopy to corroborate its identity. Final elucidation
      of the structure was performed by NMR spectroscopy.

PMID- 22989598
TI  - Comparative analysis of aspartic acid racemization methods using whole-tooth and
      dentin samples.
AB  - One way to estimate biological age is to use the aspartic acid (Asp) racemization
      method. Although this method has been performed mostly using enamel and dentin,
      we investigated whether an entire tooth can be used for age estimation. This
      study used 12 pairs of canines extracted from both sides of the mandible of 12
      individuals of known age. From each pair, one tooth was used as a dentin sample
      and the other as a whole-tooth sample. Amino acids were extracted from each
      sample, and the integrated peak areas of D-Asp and L-Asp were determined using a
      gas chromatograph/mass spectrometer. Statistical analysis was performed using the
      D/L-Asp ratio. Furthermore, teeth from two unidentified bodies, later identified
      as Japanese and Brazilian, were examined in the same manner. Results showed that
      the D/L ratios of whole-tooth samples were higher overall than those of dentin
      samples. The correlation coefficient between the D/L ratios of dentin samples and
      their age was r=0.98, and that of the whole-tooth samples was r=0.93. The
      difference between estimated age and actual chronological age was -0.116 and 
      6.86 years in the Japanese and Brazilian cases, respectively. The use of whole
      teeth makes the racemization technique easier and can standardize the sampling
      site. Additionally, using only a few tooth samples per analysis made it possible
      to reanalyze known-age samples. Although the difficulty in obtaining a proper
      control sample has prevented racemization from being widely used, the method
      described here not only ensures the availability of a control tooth, but also
      enables the teeth to be used for other purposes such as DNA analysis. The use of
      a whole tooth will increase the application of the racemization technique for age
      determination.

PMID- 22989600
TI  - Detection of metal residues on bone using SEM-EDS. Part I: Blunt force injury.
AB  - Previous studies have indicated that metal particles remain on bone after sharp
      force injury or gunshot and that their detection by scanning electron microscopy
      with energy dispersive X-ray spectrometry (SEM-EDS) could greatly help in tool
      identification. However, the presence of metal particles on bone surfaces in the
      context of blunt force trauma has never been assessed experimentally. For this
      reason the present paper represents an experimental study of the behaviour of
      metal residues on bone following blunt force injury. Ten fresh sub-adult bovine
      metatarsal bones were manually cleaned of soft tissues. They were then struck by
      metal bars (copper, iron or aluminium) on the external surface of the mid
      diaphysis. All blunt metal instruments used in this study left a sign in the form
      of single particles, a smear or a powder-like deposit on the bone surface. The
      residues of all three metal implements were detected on the bone surface, 0.3-10
      mm from the fracture border. The presence of metal particles was confirmed in all
      samples struck with iron and copper and in two of six aluminium samples; no
      particles were detected on the negative control. Chemical composition of residues
      highly corresponded with the composition of applied bars.

PMID- 22989601
TI  - Chemical profiling of seized methamphetamine putatively synthesized from
      phenylacetic acid derivatives.
AB  - We report a case of seized crystalline methamphetamine (MA) samples showing
      unique drug profiles. The samples were mainly composed of (S)-(+)-MA, with each
      containing a slight amount of (R)-(-)-MA (enantiomeric excess: 99.2-99.4%). 1
      Phenyl-2-propanol and N-methyl-2-phenylacetamide were detected as characteristic
      impurities. These analytical results suggested that the samples were synthesized
      as racemic MA by reductive amination of 1-phenyl-2-propanone, which was
      synthesized from phenylacetic acid, putatively prepared from phenylacetic acid
      ester, and then the racemic MA was optically resolved to the (+)-form-rich
      product. This proposed preparation route was in accordance with recent reports of
      seizures worldwide of the raw materials of MA such as phenylacetic acid
      derivatives, methylamine, and tartaric acid (optical resolving reagent).

PMID- 22989602
TI  - Transition in Duchenne muscular dystrophy: An expert meeting report and
      description of transition needs in an emergent patient population: (Parent
      Project Muscular Dystrophy Transition Expert Meeting 17-18 June 2011, Amsterdam,
      The Netherlands).

PMID- 22989603
TI  - Novel oral anticoagulants in acute coronary syndrome.
AB  - Coronary artery disease (CAD) is a leading cause of morbidity and mortality
      worldwide with a prevalence that has now reached pandemic levels as a consequence
      of the rapid modernization of the developing world. Its presentation as an acute
      coronary syndrome (ACS) is a frequent reason for hospital admission and of
      profound implications for personal, societal and global health. Despite
      improvements in the management of ACS with anti-platelet and anticoagulant
      therapy and revascularization techniques, many patients continue to suffer
      recurrent ischemic events. The need to reduce future cardiovascular events has
      led to the development of novel therapies to prevent coronary thrombosis,
      targeting thrombin-mediated pathways. These include direct Xa inhibitors
      (apixaban, rivaroxaban and darexaban), direct thrombin inhibitors (dabigatran)
      and PAR 1 antagonists (vorapaxar and atopaxar). This article critically reviews
      the comparative mechanisms of action, the risks and benefits, together with the
      clinical evidence base for the use of these novel oral agents in the management
      of ACS patients. 

PMID- 22989604
TI  - Acute exercise induce endothelial nitric oxide synthase phosphorylation via Akt
      and AMP-activated protein kinase in aorta of rats: Role of reactive oxygen
      species.
AB  - BACKGROUND: Acute exercise increases reactive oxygen species (ROS) levels,
      including hydrogen peroxide (H2O2). H2O2 promotes endothelial nitric oxide
      synthase (eNOS) activation and phosphorylation in endothelial cells. With this in
      mind, the present study was designed to evaluate ex vivo eNOS phosphorylation in
      rat aortas incubated with H2O2 and to test this hypothesis in vivo in the aortas
      of rats submitted to acute exercise. METHODS: For ex vivo studies, six groups of
      aortic tissue were formed: control, H2O2, N-acetylcysteine (NAC), LY294002,
      compound C, and LY294002 plus compound C. While incubation with H2O2 increased
      Akt, AMPK and eNOS phosphorylation, pre-incubation with NAC strongly reduced the
      phosphorylation of these enzymes. For in vivo studies, male Wistar rats were
      divided into four groups: control, cont+NAC, exercise, and exer+NAC. After a 3h
      swimming session, animals were decapitated and aortas were excised for
      biochemical and immunoblotting analysis. RESULTS: Acute exercise increased
      superoxide levels and dichlorofluorescein (DCF) concentrations, and this increase
      was related to phosphorylation of Akt, AMPK and eNOS. On the other hand, use of
      NAC reduced superoxide levels and DCF concentration. Reduced superoxide levels
      and DCF in the exer+NAC group were associated with decreased Akt, AMPK and eNOS
      phosphorylation. These results appear to be connected with vascular function
      because VASP phosphorylation increased in acute exercise and decreased in
      exer+NAC. CONCLUSION: Our results indicate that ROS induced by acute exercise
      play the important role of activating eNOS, a process apparently mediated by Akt
      and AMPK.

PMID- 22989605
TI  - Decreased endogenous secretory RAGE and increased hsCRP levels in serum are
      associated with atrial fibrillation in patients undergoing coronary angiography.

PMID- 22989606
TI  - Are prostate-specific antigen levels predictors of acute coronary syndrome or
      atrial fibrillation?

PMID- 22989607
TI  - Incident thromboembolism and heart failure associated with new-onset atrial
      fibrillation in cancer patients.

PMID- 22989608
TI  - Ventricular fibrillation and life-threatening ventricular tachycardia in the
      setting of outflow tract arrhythmias--the place of ICD therapy.

PMID- 22989609
TI  - Implantable defibrillators in cardiac amyloidosis.

PMID- 22989610
TI  - Imbalance of interneuron distribution between neocortex and basal ganglia:
      consideration of epileptogenesis of focal cortical dysplasia.
AB  - AIM: The balance of excitation and inhibition of neurons and neuronal network is
      very important to perform complete neuronal function. Damage or loss of
      inhibitory gamma-aminobutyric acid (GABA)-ergic interneuron is associated with
      impaired inhibitory control of cortical pyramidal neurons, leading to
      hyperexcitability and epileptogenesis. Ectopic neurons in the basal ganglia are
      to be one of the pathological features of epileptogenesis. In the present study,
      we investigated distribution of interneuron subtypes between neocortex and
      caudate nucleus. METHODS: We performed immunohistochemistry of GABA, glutamic
      acid decarboxylase (GAD), calretinin (CR), calbindin (CB), parvalbumin (PV) and
      neuropeptide. We used surgical materials of four focal cortical dysplasia (FCD)
      cases, having lesions of neocortex and caudate nucleus, and eight age-matched
      autopsy controls. RESULTS: The pathology showed three FCD IIa, containing
      dysmorphic neurons, and one FCD IIb, balloon cells. In the neocortex, the
      concentrations (each positive cell number/all cell numbers in the evaluated
      field) of GAD+, CR+ and CB+ cells were significantly lower in FCD than in
      controls. On the contrary, in the caudate nucleus those of CR+ and CB+ cells were
      significantly more in FCD than in controls. CONCLUSION: The interneuron imbalance
      between the neocortex and basal ganglia may affect the epileptogenesis of FCD.

PMID- 22989611
TI  - Tracheostomy mechanical ventilation in patients with amyotrophic lateral
      sclerosis: clinical features and survival analysis.
AB  - BACKGROUND: Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic
      lateral sclerosis (ALS) patients with a respiratory failure or when the non
      invasive ventilation (NIV) is no longer effective. We evaluated the clinical
      characteristics and survival of a cohort of tracheostomized ALS patients,
      followed in a single ALS Clinical Center. METHODS: Between 2001 and 2010, 87 out
      of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in
      25. After tracheostomy, most patients were followed up through telephone
      interviews to caregivers. A complete survival analysis could be performed in
      fifty-two TMV patients. RESULTS: 31.3% ALS patients underwent tracheostomy, with
      a male prevalence (M/F=1.69) and a median age of 61 years (interquartile range=47
      66). After tracheostomy, nearly all patients were under home care. TMV ALS
      patients were more likely than non-tracheostomized (NT) patients to be implanted
      with a PEG device, although the bulbar-/spinal-onset ratio did not differ between
      the two groups. Kaplan-Meyer analysis showed that tracheostomy increases median
      survival (TMV, 47 months vs NT, 31 months, p=0.008), with the greatest effect in
      patients younger than 60 at onset (TMV <= 60 years, 57.5 months vs NT <= 60
      years, 38.5 months, p=0.002). CONCLUSIONS: TMV is increasingly performed in ALS
      patients. Nearly all TMV patients live at home and most of them are fed through a
      PEG device. Survival after tracheostomy is generally increased, with the stronger
      effect in patients younger than 60. This survival advantage is apparently lost
      when TMV is performed in patients older than 60. The results of this study might
      be useful for the decision-making process of patients and their families about
      this advanced palliative care.

PMID- 22989612
TI  - Premorbid physical activity predicts disability progression in relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: Disability progression is a hallmark feature of multiple sclerosis
      (MS) that has been predicted by a variety of demographic and clinical variables
      and treatment with disease modifying therapies. This study examined premorbid
      physical activity as a predictor of change in disability over 24 months in
      persons with relapsing-remitting MS (RRMS). METHODS: 269 persons with RRMS
      completed baseline measures of demographic and clinical variables, premorbid and
      current physical activity, and disability status. The measure of disability was
      further completed every six months over the subsequent 24-month period. The data
      were analyzed with unconditional and conditional latent growth curve modeling
      (LGCM). RESULTS: The unconditional LGCM indicated that there was a significant,
      linear increase in disability scores over time (p=.0015). The conditional LGCM
      indicated that premorbid physical activity significantly predicted the linear
      change in disability scores (standardized beta=-.23, p<.005); current physical
      activity (standardized beta=-.02, p=.81), gender (standardized beta=-.06, p=.54),
      age (standardized beta=.05, p=.56), duration of MS (standardized beta=.11,
      p=.15), and treatment with disease modifying therapies (standardized beta=-.03,
      p=.77) did not predict change in disability scores. CONCLUSIONS: The current
      research highlights the possible role of premorbid physical activity for
      lessening disability progression over time in persons with RRMS. Additional
      research is necessary on physical activity initiated after the diagnosis of RRMS
      as a lifestyle approach for bolstering physiological reserve and preventing
      disability progression.

PMID- 22989613
TI  - Challenges in diagnosis of young onset Parkinson's disease.
AB  - Young onset Parkinson's disease patients, typically aged 21 to between 40 and 55,
      have symptomatology similar to regular onset patients. Despite this, we suspect
      that physicians take longer to diagnose young onset patients since Parkinson's
      disease is ruled out due to the younger age. The history prior to diagnosis of 14
      young onset patients (within 21 to 45 years of age) was compared with an
      equivalent number of regular onset patients matched by gender, tremor presence,
      and Hoehn and Yahr stage. Indeed, a longer period of time was taken to diagnose
      younger patients with an average of additional 15 months (p<0.001). This trend of
      older patients being diagnosed sooner was present in the regular onset group
      analyzed in isolation, but not so for the younger group. The lack of age
      dependent variation in time required for diagnosis suggests that Parkinson's
      disease is not considered at all in the diagnosis for an extended period,
      accounting for the large difference in prevalence of young onset group to the
      regular onset group. We also observed a significantly higher number of
      neurologist visits (p=0.002) and clinical investigations (p<0.001) prior to
      diagnosis of young-onset patients. Due to the impact of delayed diagnoses on
      young onset patients and clinical resources, we propose that Parkinson's disease
      be more actively considered in differential diagnoses of younger patients
      presenting associated symptoms.

PMID- 22989614
TI  - Plasma monocyte chemotactic protein-1 levels at 24 hours are a biomarker of
      primary graft dysfunction after lung transplantation.
AB  - Monocyte chemotactic protein-1 (MCP-1), also known as "chemokine ligand 2"
      (CCL2), is a monocyte-attracting chemokine produced in lung epithelial cells. We
      previously reported an association of increased levels of plasma MCP-1 with
      primary graft dysfunction (PGD) after lung transplantation in a nested case
      control study of extreme phenotypes using a multiplex platform. In this study, we
      sought to evaluate the role of plasma MCP-1 level as a biomarker across the full
      spectrum of PGD. We performed a prospective cohort study of 108 lung transplant
      recipients within the Lung Transplant Outcomes Group cohort. Plasma MCP-1 levels
      were measured pretransplantation and 6 and 24 hours after transplantation. The
      primary outcome was development of grade 3 PGD within 72 hours of transplant,
      with secondary analyses at the 72-hour time point. Multivariable logistic
      regression was used to evaluate confounding. Thirty subjects (28%) developed PGD.
      Median MCP-1 measured at 24 hours post-transplant was elevated in subjects with
      PGD (167.95 vs 103.5 pg/mL, P = .04). MCP-1 levels at 24 hours were associated
      with increased odds of grade 3 PGD after lung transplantation (odds ratio for
      each 100 pg/mL, 1.24; 95% confidence interval, 1.00-1.53) and with grade 3 PGD
      present at the 72-hour time point (odds ratio for each 100 pg/mL, 1.57; 95%
      confidence interval, 1.18-2.08), independent of confounding variables in
      multivariable analyses. MCP-1 levels measured preoperatively and 6 hours after
      transplant were not significantly associated with PGD. Persistent elevations in
      MCP-1 levels at 24 hours are a biomarker of grade 3 PGD post-transplantation.
      Monocyte chemotaxis may play a role in the pathogenesis of PGD.

PMID- 22989615
TI  - Morphology and surface topography of the schistosome Bivitellobilharzia nairi
      from the Asian elephant (Elephas maximus maximus) in Sri Lanka.
AB  - Bivitellobilharzia nairi was first recorded from an Indian elephant (Elephas
      maximus) in Berlin. Infections with this parasite have become increasingly
      important in E. maximus maximus populations in Sri Lanka. The present work is the
      first morphological description of this schistosome from Sri Lanka. A number of
      adult worms were recovered from a dead Asian elephant near the elephant
      orphanage, Pinnawala, in Sri Lanka. The observed clinical features of the
      infected elephant included emaciation, subventral oedema and anaemia. Post-mortem
      results indicated that the liver was enlarged and adult schistosomes were found
      in the blood vessels of the liver parenchyma. The total number of worms recovered
      from a portion of the liver was 129,870, which is an average of 22 worms per 100
      g of liver. The present study uses both light microscopic and scanning electron
      microscope (SEM) techniques for the morphological and topographical
      characterization of this parasite and to permit comparison with other species of
      schistosomes. Morphologically, these worms correspond very well to the
      description of B. nairi by Dutt & Srivastava (1955). Moreover, it is clear that
      B. nairi is a distinctive species easily differentiated from other schistosomes.
      The SEM study of the tegument of male worms shows that the surface of B. nairi is
      smoother than in other schistosomes. 

PMID- 22989617
TI  - The HAT/HDAC interplay: multilevel control of STAT signaling.
AB  - Besides the transcription-promoting role of histone acetyltransferases (HATs) and
      the transcription-delimiting function of histone deacetylases (HDACs) through
      histone acetylation and deacetylation respectively, HATs and HDACs also regulate
      the activity of several non-histone proteins. This includes signal transducers
      and activators of transcription (STATs), key proteins in cytokine signaling.
      Unlike Tyr phosphorylation/dephosphorylation, which mainly acts as an on/off
      switch of STAT activity, the control exerted by HATs and HDACs appears
      multifaceted and far more complex than initially imagined. Our review focuses on
      the latest trends and novel hypotheses to explain differential context-dependent
      STAT regulation by complex posttranslational modification patterns. We chart the
      knowledge on how STATs interact with HATs and HDACs, and additionally bring a
      transcriptional regulatory and gene-set specific role for HDACs in the picture.
      Indeed, a growing amount of evidence demonstrates, paradoxically, that not only
      HAT but also HDAC activity can be required for STAT-dependent transcription, in a
      STAT subtype- and cell type-dependent manner. Referring to recent reports, we
      review and discuss the various molecular mechanisms that have recently been
      proposed to account for this peculiar regulation, in an attempt to shed more
      light on the difficult yet important question on how STAT specificity is being
      generated.

PMID- 22989619
TI  - Health care research unit: a challenging environment for a new context?

PMID- 22989616
TI  - Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12.
AB  - Although chemokines are well established to function in immunity and endothelial
      cell activation and proliferation, a rapidly growing literature suggests that CXC
      Chemokine receptors CXCR3, CXCR4 and CXCR7 are critical in the development and
      progression of solid tumors. The effect of these chemokine receptors in
      tumorigenesis is mediated via interactions with shared ligands I-TAC (CXCL11) and
      SDF-1 (CXCL12). Over the last decade, CXCR4 has been extensively reported to be
      overexpressed in most human solid tumors and has earned considerable attention
      toward elucidating its role in cancer metastasis. To enrich the existing
      armamentarium of anti-cancerous agents, many inhibitors of CXCL12-CXCR4 axis have
      emerged as additional or alternative agents for neo-adjuvant treatments and even
      many of them are in preclinical and clinical stages of their development.
      However, the discovery of CXCR7 as another receptor for CXCL12 with rather high
      binding affinity and recent reports about its involvement in cancer progression,
      has questioned the potential of "selective blockade" of CXCR4 as cancer
      chemotherapeutics. Interestingly, CXCR7 can also bind another chemokine CXCL11,
      which is an established ligand for CXCR3. Recent reports have documented that
      CXCR3 and their ligands are overexpressed in different solid tumors and regulate
      tumor growth and metastasis. Therefore, it is important to consider the
      interactions and crosstalk between these three chemokine receptors and their
      ligand mediated signaling cascades for the development of effective anti-cancer
      therapies. Emerging evidence also indicates that these receptors are
      differentially expressed in tumor endothelial cells as well as in cancer stem
      cells, suggesting their direct role in regulating tumor angiogenesis and
      metastasis. In this review, we will focus on the signals mediated by this
      receptor trio via their shared ligands and their role in tumor growth and
      progression.

PMID- 22989620
TI  - Characteristics of mentoring relationships formed by medical students and
      faculty.
AB  - BACKGROUND: Little is known about the characteristics of mentoring relationships
      formed between faculty and medical students. Individual mentoring relationships
      of clinical medical students at Munich Medical School were characterized
      quantitatively and qualitatively. METHODS: All students signing up for the
      mentoring program responded to a questionnaire on their expectations (n = 534).
      Mentees were asked to give feedback after each of their one-on-one meetings (n =
      203). A detailed analysis of the overall mentoring process and its
      characteristics was performed. For qualitative text analysis, free-text items
      were analyzed and categorized by two investigators. Quantitative analysis was
      performed using descriptive statistics and Wilcoxon-test to assess differences in
      grades between students with and without mentors. RESULTS: High-performing
      students were significantly more likely to participate in the mentoring program
      (p<0.001). Topics primarily discussed include the mentee's personal goals
      (65.5%), career planning (59.6%), and experiences abroad (57.6%). Mentees mostly
      perceived their mentors as counselors (88.9%), providers of ideas (85.0%), and
      role models (73.3%). Mentees emphasized the positive impact of the mentoring
      relationship on career planning (77.2%) and research (75.0%). CONCLUSIONS:
      Medical students with strong academic performance as defined by their grades are
      more likely to participate in formal mentoring programs. Mentoring relationships
      between faculty and medical students are perceived as a mutually satisfying and
      effective instrument for key issues in medical students' professional
      development. PRACTICAL IMPLICATIONS: Mentoring relationships are a highly
      effective means of enhancing the bidirectional flow of information between
      faculty and medical students. A mentoring program can thus establish a feedback
      loop enabling the educational institution to swiftly identify and address issues
      of medical students.

PMID- 22989621
TI  - Computer-based assessments of expected satiety predict behavioural measures of
      portion-size selection and food intake.
AB  - Previously, expected satiety (ES) has been measured using software and two
      dimensional pictures presented on a computer screen. In this context, ES is an
      excellent predictor of self-selected portions, when quantified using similar
      images and similar software. In the present study we sought to establish the
      veracity of ES as a predictor of behaviours associated with real foods.
      Participants (N=30) used computer software to assess their ES and ideal portion
      of three familiar foods. A real bowl of one food (pasta and sauce) was then
      presented and participants self-selected an ideal portion size. They then
      consumed the portion ad libitum. Additional measures of appetite, expected and
      actual liking, novelty, and reward, were also taken. Importantly, our screen
      based measures of expected satiety and ideal portion size were both significantly
      related to intake (p<.05). By contrast, measures of liking were relatively poor
      predictors (p>.05). In addition, consistent with previous studies, the majority
      (90%) of participants engaged in plate cleaning. Of these, 29.6% consumed more
      when prompted by the experimenter. Together, these findings further validate the
      use of screen-based measures to explore determinants of portion-size selection
      and energy intake in humans.

PMID- 22989622
TI  - The motivational and informational basis of attitudes toward foods with health
      claims.
AB  - This research explored the effects of food choice motives, nutritional knowledge,
      and the use of food labels, on attitude toward food with health claims. Food with
      health claims was chosen as a relatively novel category of products designed to
      be beneficial for health. We identified eight motives served by food in general,
      and tested if they serve as motivations to positively evaluate functional food.
      Questionnaire was administered on nationally representative samples of 3085
      respondents from six Western Balkan countries. We proposed two structural models
      relating an extensive list of eight and, alternatively, restricted list of three
      food-choice motives (health, mood and sensory appeal) to attitude toward
      functional food. We also expected the indirect association between the health
      motive and attitude, through nutritional knowledge and use of food labels. The
      results revealed highly positive, although undifferentiated attitude toward
      functional food, with no significant differences between the countries. The
      restricted model provided a better fit then the exhaustive model; the health
      motive was proven to have indirect influence on attitude through knowledge and
      label use. The implications of these findings for functional approach to
      attitudes, understanding the demand for functional food and overcoming barriers
      to dietary change are discussed.

PMID- 22989624
TI  - Neural correlates of control operations in inverse priming with relevant and
      irrelevant masks.
AB  - The inverse priming paradigm can be considered one example which demonstrates the
      operation of control processes in the absence of conscious experience of the
      inducing stimuli. Inverse priming is generated by a prime that is followed by a
      mask and a subsequent imperative target stimulus. With "relevant" masks that are
      composed of the superposition of both prime alternatives, the inverse priming
      effect is typically larger than with "irrelevant" masks that are free of task
      relevant features. We used functional magnetic resonance imaging (fMRI) to
      examine the neural substrates that are involved in the generation of inverse
      priming effects with relevant and irrelevant masks. We found a network of brain
      areas that is accessible to unconscious primes, including supplementary motor
      area (SMA), anterior insula, middle cingulate cortex, and supramarginal gyrus.
      Activation of these brain areas were involved in inverse priming when relevant
      masks were used. With irrelevant masks, however, only SMA activation was involved
      in inverse priming effects. Activation in SMA correlated with inverse priming
      effects of individual participants on reaction time, indicating that this brain
      area reflects the size of inverse priming effects on the behavioral level.
      Findings are most consistent with the view that a basic inhibitory mechanism
      contributes to inverse priming with either type of mask and additional processes
      contribute to the effect with relevant masks. This study provides new evidence
      showing that cognitive control operations in the human cortex take account of
      task relevant stimulus information even if this information is not consciously
      perceived.

PMID- 22989623
TI  - Associations between white matter microstructure and infants' working memory.
AB  - Working memory emerges in infancy and plays a privileged role in subsequent
      adaptive cognitive development. The neural networks important for the development
      of working memory during infancy remain unknown. We used diffusion tensor imaging
      (DTI) and deterministic fiber tracking to characterize the microstructure of
      white matter fiber bundles hypothesized to support working memory in 12-month-old
      infants (n=73). Here we show robust associations between infants' visuospatial
      working memory performance and microstructural characteristics of widespread
      white matter. Significant associations were found for white matter tracts that
      connect brain regions known to support working memory in older children and
      adults (genu, anterior and superior thalamic radiations, anterior cingulum,
      arcuate fasciculus, and the temporal-parietal segment). Better working memory
      scores were associated with higher FA and lower RD values in these selected white
      matter tracts. These tract-specific brain-behavior relationships accounted for a
      significant amount of individual variation above and beyond infants' gestational
      age and developmental level, as measured with the Mullen Scales of Early
      Learning. Working memory was not associated with global measures of brain volume,
      as expected, and few associations were found between working memory and control
      white matter tracts. To our knowledge, this study is among the first
      demonstrations of brain-behavior associations in infants using quantitative
      tractography. The ability to characterize subtle individual differences in infant
      brain development associated with complex cognitive functions holds promise for
      improving our understanding of normative development, biomarkers of risk,
      experience-dependent learning and neuro-cognitive periods of developmental
      plasticity.

PMID- 22989625
TI  - Representations of the temporal envelope of sounds in human auditory cortex: can
      the results from invasive intracortical "depth" electrode recordings be
      replicated using non-invasive MEG "virtual electrodes"?
AB  - Magnetoencephalography (MEG) beamformer analyses use spatial filters to estimate
      neuronal activity underlying the magnetic fields measured by the MEG sensors. MEG
      "virtual electrodes" are the outputs of beamformer spatial filters. The present
      study aimed to test the hypothesis that MEG virtual electrodes can replicate the
      findings from intracortical "depth" electrode studies relevant to the processing
      of the temporal envelopes of sounds [e.g. Nourski et al. (2009) "Temporal
      envelope of time-compressed speech represented in the human auditory cortex," J.
      Neurosci. 29:15564-15574]. Specifically we aimed to determine whether it is
      possible to use non-invasive MEG virtual electrodes to characterise the
      representation of temporal envelopes of 6-Hz sinusoidal amplitude modulation
      (SAM) and speech using both auditory evoked fields (AEFs) and patterns of power
      changes in high-frequency (>70 Hz) bands. MEG signals were analysed using a
      location of interest (LOI) approach by seeding virtual electrodes in the left and
      right posteromedial Heschl's gyri. AEFs showed phase-locking to the temporal
      envelope of SAM and speech stimuli. Time-frequency analyses revealed no clear
      differences in high gamma power between the pre-stimulus baseline and the post
      stimulus presentation periods. Nevertheless the patterns of changes in high gamma
      power were significantly correlated with the temporal envelopes of 6-Hz SAM and
      speech in the majority of participants. The present study reveals difficulties in
      replicating clear augmentations in high gamma power changes using MEG virtual
      electrodes cf. intracortical "depth" electrode studies (Nourski et al., 2009).

PMID- 22989626
TI  - Spontaneous kisspeptin neuron firing in the adult mouse reveals marked sex and
      brain region differences but no support for a direct role in negative feedback.
AB  - Kisspeptin-Gpr54 signaling is critical for the GnRH neuronal network controlling
      fertility. The present study reports on a kisspeptin (Kiss)-green fluorescent
      protein (GFP) mouse model enabling brain slice electrophysiological recordings to
      be made from Kiss neurons in the arcuate nucleus (ARN) and rostral
      periventricular region of the third ventricle (RP3V). Using dual
      immunofluorescence, approximately 90% of GFP cells in the RP3V of females, and
      ARN in both sexes, are shown to be authentic Kiss-synthesizing neurons in adult
      mice. Cell-attached recordings of ARN Kiss-GFP cells revealed a marked sex
      difference in their mean firing rates; 90% of Kiss-GFP cells in males exhibited
      slow irregular firing (0.17 +/- 0.04 Hz) whereas neurons from diestrous (0.01 +/-
      0.01 Hz) and ovariectomized (0 Hz) mice were mostly or completely silent. In
      contrast, RP3V Kiss-GFP cells were all spontaneously active, exhibiting tonic,
      irregular, and bursting firing patterns. Mean firing rates were significantly (P
      < 0.05) higher in diestrus (2.1 +/- 0.3 Hz) compared with ovariectomized (1.0 +/-
      0.2 Hz) mice without any changes in firing pattern. Recordings from RP3V Kiss-GFP
      neurons at the time of the proestrous GnRH surge revealed a significant decline
      in firing rate after the surge. Together, these observations demonstrate
      unexpected sex differences in the electrical activity of ARN Kiss neurons and
      markedly different patterns of firing by Kiss neurons in the ARN and RP3V.
      Although data supported a positive influence of gonadal steroids on RP3V Kiss
      neuron firing, no direct evidence was found to support the previously postulated
      role of ARN Kiss neurons in the estrogen-negative feedback mechanism.

PMID- 22989627
TI  - Periovulatory expression of hydrogen peroxide-induced sulfiredoxin and
      peroxiredoxin 2 in the rat ovary: gonadotropin regulation and potential
      modification.
AB  - Reactive oxygen species are involved in ovulation. The aim of this study was to
      examine gonadotropin regulation of antioxidant enzyme sulfiredoxin (Srx) and
      peroxiredoxin 2 (PRDX2) expressions and modification during the ovulatory process
      in rats. Administration of antioxidants in vivo reduced ovulation rate and
      cumulus expansion. LH treatment increased H(2)O(2) levels within 15 min, which,
      in turn, induced Srx gene expression in cultured preovulatory follicles.
      Treatment of preovulatory follicles with catalase suppressed the stimulatory
      effect of LH on Akt phosphorylation. LH- or H(2)O(2)-stimulated Srx mRNA levels
      were suppressed by inhibitors of antioxidant agents and MAPK kinase. An in vivo
      injection of equine chorionic gonadotropin-human chorionic gonadotropin (hCG)
      stimulated Srx mRNA within 1 h in granulosa but not thecal cells of preovulatory
      follicles. Srx protein levels were stimulated from 3 h post-hCG injection.
      Immunofluorescence analysis revealed that oocytes expressed the Srx protein.
      Furthermore, hCG treatment increased Srx expression in mural granulosa, theca and
      cumulus cells, but the Srx protein was not detected in corpora lutea. Gene
      expression of PRDX2, identified as an Srx-dependent modified enzyme, was
      stimulated by gonadotropins. In situ hybridization analysis demonstrated that
      PRDX2 mRNA was detected in oocytes and theca cells as well as granulosa cells of
      some antral and preovulatory follicles. High levels of PRDX2 mRNA were detected
      in corpora lutea. Total levels of PRDX2 protein were not changed by
      gonadotropins. However, levels of hyperoxidized PRDX2 increased within 2-3 h
      after the hCG injection. Taken together, gonadotropin stimulation of Srx
      expression and PRDX2 modification in the ovary suggest the existence of an
      antioxidant system to maintain H(2)O(2) production and elimination during the
      periovulatory period.

PMID- 22989629
TI  - Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle
      amplifies local insulin sensitivity.
AB  - Adiponectin is an adipokine whose plasma levels are inversely related to degrees
      of insulin resistance (IR) or obesity. It enhances glucose disposal and
      mitochondrial substrate oxidation in skeletal muscle and its actions are mediated
      through binding to receptors, especially adiponectin receptor 1 (AdipoR1).
      However, the in vivo significance of adiponectin sensitivity and the molecular
      mechanisms of muscle insulin sensitization by adiponectin have not been fully
      established. We used in vivo electrotransfer to overexpress AdipoR1 in single
      muscles of rats, some of which were fed for 6 wk with chow or high-fat diet (HFD)
      and then subjected to hyperinsulinemic-euglycemic clamp. After 1 wk, the effects
      on glucose disposal, signaling, and sphingolipid metabolism were investigated in
      test vs. contralateral control muscles. AdipoR1 overexpression (OE) increased
      glucose uptake and glycogen accumulation in the basal and insulin-treated rat
      muscle and also in the HFD-fed rats, locally ameliorating muscle IR. These
      effects were associated with increased phosphorylation of insulin receptor
      substrate-1, Akt, and glycogen synthase kinase-3beta. AdipoR1 OE also caused
      increased phosphorylation of p70S6 kinase, AMP-activated protein kinase, and
      acetyl-coA carboxylase as well as increased protein levels of adaptor protein
      containing pleckstrin homology domain, phosphotyrosine binding domain, and
      leucine zipper motif-1 and adiponectin, peroxisome proliferator activated
      receptor-gamma coactivator-1alpha, and uncoupling protein-3, indicative of
      increased mitochondrial biogenesis. Although neither HFD feeding nor AdipoR1 OE
      caused generalized changes in sphingolipids, AdipoR1 OE did reduce levels of
      sphingosine 1-phosphate, ceramide 18:1, ceramide 20:2, and dihydroceramide 20:0,
      plus mRNA levels of the ceramide synthetic enzymes serine palmitoyl transferase
      and sphingolipid Delta-4 desaturase, changes that are associated with increased
      insulin sensitivity. These data demonstrate that enhancement of local adiponectin
      sensitivity is sufficient to improve skeletal muscle IR.

PMID- 22989630
TI  - Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis.
AB  - Glucocorticoids and their synthetic derivatives are known to alter cardiac
      function in vivo; however, the nature of these effects and whether
      glucocorticoids act directly on cardiomyocytes are poorly understood. To explore
      the role of glucocorticoid signaling in the heart, we used rat embryonic H9C2
      cardiomyocytes and primary cardiomyocytes as model systems. Dexamethasone (100
      nm) treatment of cardiomyocytes caused a significant increase in cell size and up
      regulated the expression of cardiac hypertrophic markers, including atrial
      natriuretic factor, beta-myosin heavy chain, and skeletal muscle alpha-actin. In
      contrast, serum deprivation and TNFalpha exposure triggered cardiomyocyte
      apoptosis, and these apoptotic effects were inhibited by dexamethasone. Both the
      hypertrophic and anti-apoptotic actions of glucocorticoids were abolished by the
      glucocorticoid receptor (GR) antagonist RU486 and by short hairpin RNA-mediated
      GR depletion. Blocking the activity of the mineralocorticoid receptor had no
      effect on these glucocorticoid-dependent cardiomyocyte responses. Aldosterone (1
      MUm) activation of GR also promoted cardiomyocyte hypertrophy and cell survival.
      To elucidate the mechanism of the dual glucocorticoid actions, a genome-wide
      microarray was performed on H9C2 cardiomyocytes treated with vehicle or
      dexamethasone in the absence or presence of serum. Serum dramatically influenced
      the transcriptome regulated by GR, revealing potential glucocorticoid signaling
      mediators in both cardiomyocyte hypertrophy and apoptosis. These studies reveal a
      direct and dynamic role for glucocorticoids and GR signaling in the modulation of
      cardiomyocyte function.

PMID- 22989628
TI  - Kisspeptin neurons from mice to men: similarities and differences.
AB  - The discovery that kisspeptin was critical for normal fertility in humans ushered
      in a new chapter in our understanding of the control of GnRH secretion. In this
      paper, we will review recent data on the similarities and differences across
      several mammalian species in the role of kisspeptin in reproductive
      neuroendocrinology. In all mammals examined to date, there is strong evidence
      that kisspeptin plays a key role in the onset of puberty and is necessary for
      both tonic and surge secretion of GnRH in adults, although kisspeptin-independent
      systems are also apparent in these studies. Similarly, two groups of kisspeptin
      neurons, one in the arcuate nucleus (ARC) and the other more rostrally, have been
      identified in all mammals, although the latter is concentrated in a limited area
      in rodents and more scattered in other species. Estrogen has divergent actions on
      kisspeptin expression in these two regions across these species, stimulating it
      the latter and inhibiting expression in the former. There is also strong evidence
      that the rostral population participates in the GnRH surge, whereas the ARC
      population contributes to steroid-negative feedback. There may be species
      differences in the role of these two populations in puberty, with the ARC cells
      important in rats, sheep, and monkeys, whereas both have been implicated in mice.
      ARC kisspeptin neurons also appear to participate in the GnRH surge in sheep and
      guinea pigs, whereas the data on this possibility in rodents are contradictory.
      Similarly, both populations are sexually dimorphic in sheep and humans, whereas
      most data in rodents indicate that this occurs only in the rostral population.
      The functional consequences of these species differences remain to be fully
      elucidated but are likely to have significance for understanding normal
      neuroendocrine control of reproduction as well as for use of kisspeptin
      agonists/antagonists as a therapeutic tool.

PMID- 22989631
TI  - KNDy (kisspeptin/neurokinin B/dynorphin) neurons are activated during both
      pulsatile and surge secretion of LH in the ewe.
AB  - KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC)
      appear to mediate the negative feedback actions of estradiol and are thought to
      be key regulators of pulsatile LH secretion. In the ewe, KNDy neurons may also be
      involved with the positive feedback actions of estradiol (E(2)) to induce the LH
      surge, but the role of kisspeptin neurons in the preoptic area (POA) remains
      unclear. The goal of this study was to identify which population(s) of kisspeptin
      neurons is (are) activated during the LH surge and in response to the removal of
      E(2)-negative feedback, using Fos as an index of neuronal activation. Dual-label
      immunocytochemistry for kisspeptin and Fos was performed on sections containing
      the ARC and POA from ewes during the luteal phase of the estrous cycle, or before
      or after the onset of the LH surge (experiment 1), and from ovary-intact, short
      term (24 h) and long-term (>30 d) ovariectomized (OVX) ewes in anestrus
      (experiment 2). The percentage of kisspeptin neurons expressing Fos in both the
      ARC and POA was significantly higher during the LH surge. In contrast, the
      percentage of kisspeptin/Fos colocalization was significantly increased in the
      ARC, but not POA, after both short- and long-term E(2) withdrawal. Thus, POA
      kisspeptin neurons in the sheep are activated during, and appear to contribute
      to, E(2)-positive feedback, whereas ARC kisspeptin (KNDy) neurons are activated
      during both surge and pulsatile modes of secretion and likely play a role in
      mediating both positive and negative feedback actions of E(2) on GnRH secretion
      in the ewe.

PMID- 22989632
TI  - Experimental and modeling study of a two-stage pilot scale high solid anaerobic
      digester system.
AB  - This study established a comprehensive model to configure a new two-stage high
      solid anaerobic digester (HSAD) system designed for highly degradable organic
      fraction of municipal solid wastes (OFMSW). The HSAD reactor as the first stage
      was naturally separated into two zones due to biogas floatation and low specific
      gravity of solid waste. The solid waste was retained in the upper zone while only
      the liquid leachate resided in the lower zone of the HSAD reactor. Continuous
      stirred-tank reactor (CSTR) and advective-diffusive reactor (ADR) models were
      constructed in series to describe the whole system. Anaerobic digestion model No.
      1 (ADM1) was used as reaction kinetics and incorporated into each reactor module.
      Compared with the experimental data, the simulation results indicated that the
      model was able to well predict the pH, volatile fatty acid (VFA) and biogas
      production.

PMID- 22989633
TI  - Synergetic pretreatment of waste activated sludge by Fe(II)-activated persulfate
      oxidation under mild temperature for enhanced dewaterability.
AB  - The potential benefits of Fe(II)-activated persulfate (S(2)O(8)(2-)) oxidation
      under mild temperature in enhancing the dewaterability of waste activated sludge
      were investigated. Capillary suction time (CST) was used to characterize sludge
      dewatering. Zeta potential, particle size distribution, three-dimensional
      excitation-emission matrix (EEM) fluorescence spectroscopy, fourier-transformed
      infrared (FT-IR) spectroscopy and scanning electronic microscopy (SEM) were
      employed to explore influencing mechanisms. The results indicated that the
      dewaterability was deteriorated with single thermal treatment, but significantly
      enhanced in the presence of Fe(II)-S(2)O(8)(2-) oxidation and further advanced
      together with thermal treatment. EEM and FT-IR analysis indicated that combined
      thermal and Fe(II)-S(2)O(8)(2-) oxidation pretreatment led to degrading of
      tyrosine and tryptophan protein-like substances in extracellular polymeric
      substances (EPS) and cleavage of linkages in polymeric backbone. SEM images
      further revealed the rupture of sludge flocs at the colloidal scale, which
      contributed to the release of EPS-bound water and interstitial water trapped
      between flocs, and subsequent enhanced dewaterability.

PMID- 22989634
TI  - Use of Bio-Amp, a commercial bio-additive for the treatment of grease trap
      wastewater containing fat, oil, and grease.
AB  - This research investigated the application of Bio-Amp, a commercial bio-additive
      for the treatment of fat, oil, and grease (FOG) in a grease trap, and evaluated
      potential impacts of treated effluent on downstream collection system and
      treatment processes. Results show that after Bio-Amp treatment, FOG deposit
      formation was reduced by 40%, implicating a potential reduction of sewer line
      blockages. Chemical oxygen demand (COD), total nitrogen (TN), total phosphorus
      (TP) and total fatty acids were reduced by 39%, 33%, 56%, and 59%, respectively,
      which represents an overall loading reduction of 9% COD, 5% TN and 40% TP
      received by the treatment plant from all the dining halls. On the other hand,
      readily biodegradable COD fractions significantly increased, which implies a
      potential improvement on Bio-P removal. Overall, the results showed that
      application of Bio-Amp in grease trap provides potential reduction of sewer line
      blockages, and can also alleviate downstream treatment burden.

PMID- 22989635
TI  - Importance of heat transfer in an anaerobic digestion plant in a continental
      climate context.
AB  - Investigation on the sensivity to temperature variations has been achieved on a
      full-scale experimental dairy wastewater treatment plant including an unheated
      but insulated upflow anaerobic sludge blanket. A simple steady-state heat
      transfer model based on energy balance has been designed to forecast the biogas
      production depending on ambient air and dairy wastewater temperatures variations.
      Energy balance has been described for any part of the digestion plant. Calculated
      heat losses were in the same range than observed losses with an uncertainty of
      about 10%. From the equalization tank to the digester the average heat loss under
      cold period was close to 10 degrees C due to convection and conduction.
      Mesophilic conditions are not respected for couples of ambient air and wastewater
      temperatures ranging respectively from 8-35 to 35-29 degrees C. Technical
      solutions are suggested to increase the biogas production.

PMID- 22989636
TI  - Syntrophic interactions drive the hydrogen production from glucose at low
      temperature in microbial electrolysis cells.
AB  - H(2) can be obtained from glucose by fermentation at mesophilic temperatures, but
      here we demonstrate that hydrogen can also be obtained from glucose at low
      temperatures using microbial electrolysis cells (MECs). H(2) was produced from
      glucose at 4 degrees C in single-chamber MECs at a yield of about 6 mol H(2)mol(
      1) glucose, and at rates of 0.25+/-0.03-0.37+/-0.04 m(3) H(2)m(-3)d(-1).
      Pyrosequencing of 16S rRNA gene and electrochemical analyses showed that
      syntrophic interactions combining glucose fermentation with the oxidization of
      fermentation products by exoelectrogens was the predominant pathway for current
      production at a low temperature other than direct glucose oxidization by
      exoelectrogens. Another syntrophic interaction, methanogenesis and
      homoacetogenesis, which have been found in 25 degrees C reactors, were not
      detected in MECs at 4 degrees C. These results demonstrate the feasibility of
      H(2) production from abundant biomass of carbohydrates at low temperature in
      MECs.

PMID- 22989637
TI  - High level lipid production by a novel inulinase-producing yeast Pichia
      guilliermondii Pcla22.
AB  - In this study, an inulinase-producing yeast strain Pcla22 of Pichia
      guilliermondii was identified. It was found that the yeast strain Pcla22 could
      produce higher amount of oil and more lipid bodies in its cells than any other
      yeast strains tested in this study. Under the optimal conditions, 60.6%(w/w) of
      lipid based on cell dry weight, 20.4 g/l of the dry cell mass, SCO produced per g
      of consumed sugar of 0.19 g/g and biomass produced per g of consumed sugar of
      0.32 g/g were obtained in the culture of the yeast strain Pcla22 after 96 h of
      the fed-batch fermentation. Over 79.8% of the fatty acids from the yeast strain
      Pcla22 grown in the oil production medium containing inulin was C(16:0) and
      C(18:1), especially C(18:1) (57.9%). The biodiesel obtained from the produced
      lipid could be burnt well.

PMID- 22989638
TI  - Formation of liquid and solid products from liquid phase pyrolysis.
AB  - The aim of the present work was to improve the C:O ratio in biomass by preserving
      the lignin macrostructure of lignocellulosic feed. The intention of liquid phase
      pyrolysis is to liquefy biomass and prepare biomass for further upgrading steps
      like hydrogenation and deoxygenation. Pyrolysis was carried out in a non-aqueous
      liquid phase heat carrier. The process was carried out in a semi-batch reaction
      vessel under isothermal conditions at T=350 degrees C, supported by a quench to
      stop reactions instantaneously in order to observe formation of solid
      intermediates. This pyrolysis system enables the observation of liquid and solid
      product formation. Transformation of biomass into biochar was analyzed by
      infrared spectroscopy and elemental analysis. Stable lignin structure throughout
      the whole transformation was confirmed. It was shown that the lignin frame in
      wood remains without substantial loss, while the major amount of carbohydrates is
      pyrolyzed during liquid phase pyrolysis at T=350 degrees C.

PMID- 22989639
TI  - Pretreatment as the crucial step for a cellulosic ethanol biorefinery: testing
      the efficiency of wet explosion on different types of biomass.
AB  - The efficiency of wet explosion applied as modified dilute acid pretreatment at
      previously identified reference conditions (150 degrees C, 0.3% H(2)SO(4), 15
      min) was investigated on lucerne, ryegrass, fescue grass, cocksfoot grass, rye
      fescue, forage grass, and wheat straw in order to identify their potential as
      feedstock for cellulosic bioethanol production. After pretreatment, cellulose
      recovery was more than 95% for all biomass while enzymatic convertibility of
      cellulose ranged from 40% to 80%. Lower enzymatic conversion of cellulose was
      correlated with higher lignin content of the biomass. Hemicellulose recovery was
      81-91% with a final pentose yield of 65-85%. Cocksfoot grass and wheat straw had
      the highest bioethanol potential of 292 and 308 L/ton DM, respectively. Overall
      efficiencies were higher than 68% for cocksfoot grass harvested in August, fescue
      grass, wheat straw, and forage grass while efficiencies were lower than 61% for
      the other tested biomass resources, making further adjustment of the process
      parameters necessary.

PMID- 22989640
TI  - Physicochemical properties and trace organic compounds in a dairy processor's
      aerobic bioreactor.
AB  - Wastewater samples were taken from an aerobic bioreactor, operated by a dairy
      processor in southeastern Australia to reduce nutrient and pollutant loads.
      Samples were taken over a two-year period, to determine whether trace organic
      compounds or physicochemical analyses of the wastewater could be used to
      discriminate the water taken before, during and after processing of the
      wastewater in the bioreactor. Multivariate analyses of the physicochemical data
      suggested that nitrate, pH and total dissolved nitrogen best described the infeed
      wastewater entering the bioreactor, while organic and particulate phosphorus
      concentrations where predominantly responsible for describing the composition of
      the content of the bioreactor. Gas chromatography-mass spectrometry data of
      organic compounds within the wastewater samples were also analysed via
      multivariate analyses. The analyses found that the compound 4-nitrophenol was
      associated with ammonia concentrations and mixed liquor wastewater. Therefore, 4
      nitrophenol may possibly be used to act as an indicator of anaerobicity in
      aerobic bioreactors.

PMID- 22989641
TI  - Biodegradation of benzene homologues in contaminated sediment of the East China
      Sea.
AB  - This study focused on acclimating a microbial enrichment to biodegrade benzene,
      toluene, ethylbenzene and xylenes (BTEX) in a wide range of salinity. The
      enrichment degraded 120 mg/L toluene within 5d in the presence of 2M NaCl or 150
      mg/L toluene within 7d in the presence of 1-1.5M NaCl. PCR-DGGE (polymerase chain
      reaction-denatured gradient gel electrophoresis) profiles demonstrated the
      dominant species in the enrichments distributed between five main phyla:
      Gammaproteobacteria, Sphingobacteriia, Prolixibacter, Flavobacteriia and
      Firmicutes. The Marinobacter, Prolixibacter, Balneola, Zunongwangia, Halobacillus
      were the dominant genus. PCR detection of genotypes involved in bacterial BETX
      degradation revealed that the degradation pathways contained all the known
      initial oxidative attack of BTEX by monooxygenase and dioxygenase. And the
      subsequent ring fission was catalysed by catechol 1,2-dioxygenase and catechol
      2,3-dioxygenase. Nuclear magnetic resonance (NMR) spectroscopy profiles showed
      that the bacterial consortium adjusted the osmotic pressure by ectoine and
      hydroxyectoine as compatible solutes to acclimate the different salinity
      conditions.

PMID- 22989642
TI  - Modeling algal growth in bubble columns under sparging with CO2-enriched air.
AB  - A theoretical model for predicting biomass growth in semi-continuous mode under
      sparging with CO(2)-enriched air was developed. The model includes gas-to-liquid
      mass transfer, algal uptake of carbon dioxide, algal growth kinetics, and light
      and temperature effects. The model was validated using experimental data on
      growth of two microalgal species in an internally illuminated photobioreactor:
      Nannochloropsis salina under gas flow rates of 800 and 1200 mL min(-1) and CO(2)
      enrichments of 0.5, 1, and 2%; and Scenedesmus sp. at a gas flow rate of 800 mL
      min(-1) and CO(2) enrichments of 3 and 4%. Temporal algal concentration profiles
      predicted by the model under semi-continuous mode with harvesting under the
      different test conditions agreed well with the measured data, with r(2) values
      ranging from 0.817 to 0.944, p<0.001. As demonstrated, this model can be
      beneficial in predicting temporal variations in algal concentration and in
      scheduling harvesting operations under semi-continuous cultivation mode.

PMID- 22989643
TI  - Concentration and speciation of heavy metals during water hyacinth composting.
AB  - The Tessier sequential extraction method was employed to investigate the changes
      in heavy metals speciation (Zn, Cu, Mn, Fe, Pb, Ni, Cd and Cr) during water
      hyacinth (Eichhornia crassipes) composting. Results showed that, the contents of
      total metals concentration were increased during the composting process. The
      largest proportion of metals was found in the residual fraction which was in more
      stable form and is consequently considered unavailable for plant uptake.
      Reducible and oxidizable fractions of Ni, Pb and Cd were not found in all trials
      during water hyacinth composting. The concentrations of Cu and Cd were very low
      comparative to the other metals, but the percentage of exchangeable and carbonate
      fractions were similar as other metals. From this study it can be concluded that
      the appropriate proportion of cattle manure addition (Trial 4) significantly
      reduced the mobile and easily available fractions (exchangeable and carbonate
      fractions) during the composting process.

PMID- 22989644
TI  - The effects of Bacillus subtilis on nitrogen recycling from aquaculture solid
      waste using heterotrophic nitrogen assimilation in sequencing batch reactors.
AB  - A sequencing batch reactor (SBR) supplied with Bacillus subtilis (treatment
      group) was employed to treat the sludge from a re-circulating aquaculture system
      (RAS). The crude protein content of bio-flocs from the treatment group increased
      from 21.52%+/-1.5% to 29.65%+/-13.34%, which was 23.97%+/-11.62% greater than
      that of the SBRs without B. subtilis (control group). The removal rate of
      dissolved inorganic nitrogen (RR(DIN)) for the treatment group was 0.41+/-0.079
      mg L(-1)d(-1), which was 1.17 times greater than that of the control group. The
      utility rate of total organic nitrogen (UR(TON)) for the treatment group was
      1.42+/-0.33 mg L(-1)d(-1), which was 1.71 times greater than the control. The
      removal rate of dissolved organic carbon (RR(DOC)) for the treatment group was
      138.39+/-7.77 mg L(-1)d(-1), which was 1.95 times greater than the control. The
      extra-cellular polymer substance (EPS) was primarily composed of polysaccharides.
      The flocs volume after 5 min (FV-5 min) reached 22.67%+/-2.08% at 19 days.

PMID- 22989645
TI  - Characterization of the liquid product obtained by pyrolysis of karanja seed.
AB  - Karanja (Pongamia glabra) seeds were pyrolyzed in semi-batch mode at a
      temperature range of 450-550 degrees C and at a heating rate of 20 degrees C/min.
      FTIR (Fourier transform infrared spectroscopy) analysis of the liquid product
      indicates the presence of alkanes, alkenes, ketones, carboxylic acids and
      aromatics rings. GC-MS (Gas chromatography-Mass spectrometry) demonstrated the
      presence of hydrocarbons with between 14 and 31 carbon atoms in a chain. The
      physical properties of the pyrolysis liquid were close to mixture of diesel and
      petrol.

PMID- 22989646
TI  - Direct liquefaction of Dunaliella tertiolecta for bio-oil in sub/supercritical
      ethanol-water.
AB  - This paper presents bio-oil preparation by direct liquefaction of Dunaliella
      tertiolecta (D. tertiolecta) with sub/supercritical ethanol-water as the medium
      in a batch autoclave with high temperature and high pressure. The results
      indicated that ethanol and water showed synergistic effects on direct
      liquefaction of D. tertiolecta. The maximum bio-oil yield was 64.68%, with an
      optimal D. tertiolecta conversion of 98.24% in sub/supercritical ethanol-water.
      The detailed chemical compositional analysis of the bio-oil was performed using
      an EA, FT-IR, and GC-MS. The empirical formulas of the bio-oil obtained using the
      ethanol-water co-solvent (40%, v/v) and sole water as the reaction medium were
      CH(1.52)O(0.14)N(0.06) and CH(1.43)O(0.23)N(0.09), with calorific values of 34.96
      and 29.80 MJ kg(-1), respectively. XPS and SEM results showed that ethanol-water
      is a very effective reaction medium in the liquefaction. A plausible reaction
      mechanism of the main chemical component in D. tertiolecta is proposed based on
      our results and the literatures.

PMID- 22989647
TI  - Characterization of a microbial fuel cell with reticulated carbon foam
      electrodes.
AB  - A microbial fuel cell with open-pore reticulated vitreous carbon electrodes is
      studied to assess the suitability of this material in a batch mode, in the
      perspective of flow-through reactors for wastewater treatment with electricity
      generation. The cell shows good stability and fair robustness in regards to
      substrate cycles. A power density of 40 W/m(3) is reached. The cell efficiency is
      mainly limited by cathodic transfers, representing 85% of the global
      overpotential in open circuit. Through impedance spectrocopy, equivalent circuit
      modeling reveals the complex nature of the bioelectrochemical phenomena. The
      global electrical behavior of the cell seems to result in the addition of three
      anodic and two cathodic distinct phenomena. On the cathode side, the Warburg
      element in the model is related to the diffusion of oxygen. Warburg resistance
      and time are respectively 2.99 kOmega cm(2) and 16.4s, similar to those published
      elsewhere.

PMID- 22989649
TI  - Effect of microbial treatment on the prevention and removal of paraffin deposits
      on stainless steel surfaces.
AB  - In this study, biosurfactant-producing strain N2 and non-biosurfactant producing
      stain KB18 were used to investigate the effects of microbial treatment on the
      prevention and removal of paraffin deposits on stainless steel surfaces. Strain
      N2, with a biosurfactant production capacity, reduced the contact angle of
      stainless steel to 40.04 degrees , and the corresponding adhesion work of aqueous
      phase was decreased by 26.5 mJ/m(2). By contrast, KB18 could only reduce the
      contact angle to 50.83 degrees , with a corresponding 7.6 mJ/m(2) decrease in the
      aqueous phase work adhesion. The paraffin removal test showed that the paraffin
      removal efficiencies of strain N2 and KB18 were 79.0% and 61.2%, respectively.
      Interestingly, the N2 cells could attach on the surface of the oil droplets to
      inhibit droplets coalescence. These results indicate that biosurfactant-producing
      strains can alter the wettability of stainless steel and thus eliminate paraffin
      deposition.

PMID- 22989648
TI  - Development of Bio-PORec(r) system for polyhydroxyalkanoates (PHA) production and
      its storage in mixed cultures of palm oil mill effluent (POME).
AB  - High PHA production and storage using palm oil mill effluent (POME) was
      investigated using a laboratory batch Bio-PORec(r) system under aerobic-feeding
      conditions. Results showed that maximum PHA was obtained at a specific rate
      (q(p)) of 0.343 C-mol/C-molh when air was supplied at 20 ml/min. The PHA yield
      was found to be 0.80 C-mol/C-mol acetic acid (HAc) at microaerophilic condition
      and the mass balance calculation showed that PHA production increased up to
      15.68+/-2.15 C-mmol/cycle. The experiments showed that short feeding rate,
      limited requirements for electron acceptors (e.g. O(2), NO(3)) and nutrients (N
      and P) showed lower tendency of glycogen accumulation and contributed more to PHA
      productivity.

PMID- 22989650
TI  - Effect of poly(vinyl acetate-acrylamide) microspheres properties and steric
      hindrance on the immobilization of Candida rugosa lipase.
AB  - Poly(vinyl acetate-acrylamide) microspheres were synthesized in the absence or
      presence of isooctane via suspension polymerization and utilized as carriers to
      immobilize Candida rugosa lipase. When the hydrophobic/hydrophilic surface
      characteristics of the microspheres were modified by changing the ratio of vinyl
      acetate (hydrophobic monomer) to acrylamide (hydrophilic monomer) from 50:50 to
      86:24, the immobilization ratio changed from 45% to 92% and the activity of the
      immobilized lipase increased from 202.5 to 598.0 U/g microsphere. Excessive
      lipase loading caused intermolecular steric hindrance, which resulted in a
      decline in lipase activity. The maximum specific activity of the immobilized
      lipase (4.65 U/mg lipase) was higher than that of free lipase (3.00 U/mg lipase),
      indicating a high activity recovery during immobilization.

PMID- 22989651
TI  - Enhanced fed-batch fermentation of 2,3-butanediol by Paenibacillus polymyxa DSM
      365.
AB  - Fed-batch fermentations for the production of 2,3-butanediol (BDL) with
      Paenibacillus polymyxa DSM 365 were investigated in 2-L-fermenters. A suitable
      micro-aerobic set-up enabled high product selectivity of up to 98% R,R-BDL
      towards meso-BDL and acetoin. Up to 111 g L(-1)R,R-BDL within 54 h could be
      achieved with sufficient supply of complex medium (yeast extract). To the best of
      the knowledge of the authors, this is the highest titer so far reported for P.
      polymyxa indicating its high potential as a non pathogenic BDL-producer.
      Fermentation in low nutritional medium (5 g L(-1) yeast extract) yielded up to 72
      g L(-1) BDL+acetoin (79% R,R-BDL), yet was affected by formation of
      exopolysaccharides (EPS). In the range of 30-40 degrees C EPS formation decreased
      with raising temperature although growth rate and BDL-production remained
      similar. Additionally, Tween80(r) was found to be a good additive to reduce
      viscosity caused by EPS.

PMID- 22989652
TI  - An antioxidant exopolysaccharide devoid of pro-oxidant activity produced by the
      soil bacterium Bordetella sp. B4.
AB  - An exopolysaccharide (EPS) with a molecular weight of 230 kDa, was isolated from
      Bordetella sp. B4. The EPS was identified as linear alpha-1,6-(6-methyl)-glucan
      with N-acetyl-D-glucosamine branches at alpha-1, 4-linkages by IR and NMR
      spectroscopy. The free radical scavenging capacities of EPS on 2,2'-azinobis-(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)), H(2)O(2), -OH and lipid
      peroxidation were 2-, 86-, 134- and 18-fold higher than that of ascorbic acid,
      respectively. Compared with ascorbic acid, the EPS was more effective in
      preventing DNA and protein from free radical damage induced by 2,2'-azobis (2
      amidinopropane) dihydrochloride (AAPH). More significantly, the EPS did not
      degrade DNA and protein by the pro-oxidant effect in the presence of copper ions
      and H(2)O(2). Furthermore, EPS could protect human umbilical vein endothelium
      cells (HUVECs) from high glucose-mediated damage. The production of EPS reached
      10.2 g/L in the fermentation medium containing 3.0 g/L cholesterol, suggesting
      that Bordetella sp. B4 was a potential producer of antioxidant EPS.

PMID- 22989653
TI  - Towards thermal design optimization of tubular digesters in cold climates: a heat
      transfer model.
AB  - A cold climate, low cost, tubular digester is monitored and temperatures from
      different parts of the slurry, greenhouse, and adobe walls are presented,
      discussing the thermal performance of the digester. The slurry exhibits a
      vertical gradient of 6 degrees C, with a mean value of 24.5 degrees C, while the
      ambient temperature varies from 10 degrees C to 30 degrees C, showing the
      efficiency of the system as a solar heat collector with thermal inertia. A simple
      time-dependent thermal model is developed using inputs of solar radiation, wind
      velocity, ambient temperature, and digester geometry. The model outputs include
      temperatures of the slurry, the biogas, its holding membrane and the greenhouse
      air, wall and cover. Radiative, convective and conductive heat transfer phenomena
      are considered between all system elements. The model has 0.47 degrees C (2%)
      standard error for the average slurry temperature. This model can be used to
      predict the influence of geometry and materials on the performance of the
      digester.

PMID- 22989654
TI  - Rate determination of supercritical water gasification of primary sewage sludge
      as a replacement for anaerobic digestion.
AB  - Supercritical water gasification of primary sewage sludge sampled from a local
      facility was undertaken at different solids content. The performance of the
      process was compared with the anaerobic digestion system in use at the facility
      where the samples were taken. The mass and composition of the vapor products
      documented showed that the process generates more energy per gram of feed while
      rapidly destroying more volatile solids relative to the anaerobic digestion
      process. However, the energy input requirements are greater for supercritical
      water gasification. This study defines parameters for a model of the gasification
      reaction using the power law and Arrhenius equation. The activation energy was
      estimated to be 15 kJ/mol, and the reaction order was estimated to be 0.586. This
      model allows estimation of the size of a supercritical water reactor needed to
      replace the anaerobic digesters that are currently used at the wastewater
      treatment plant.

PMID- 22989655
TI  - Anaerobic biodegradability of Category 2 animal by-products: methane potential
      and inoculum source.
AB  - Category 2 animal by-products that need to be sterilized with steam pressure
      according Regulation (EC) 1774/2002 are studied. In this work, 2 sets of
      experiments were performed in mesophilic conditions: (i) biomethane potential
      determination testing 0.5%, 2.0% and 5.0% total solids (TS), using sludge from
      the anaerobic digester of a wastewater treatment plant as inoculum; (ii)
      biodegradability tests at a constant TS concentration of 2.0% and different
      inoculum sources (digested sludge from a wastewater treatment plant; granular
      sludge from an upflow anaerobic sludge blanket reactor; leachate from a municipal
      solid waste landfill; and sludge from the slaughterhouse wastewater treatment
      anaerobic lagoon) to select the more adapted inoculum to the substrate in study.
      The higher specific methane production was of 317 mL CH(4)g(-1) VS(substrate) for
      2.0% TS. The digested sludge from the wastewater treatment plant led to the
      lowest lag-phase period and higher methane potential rate.

PMID- 22989656
TI  - Effects of sodium carbonate pretreatment on the chemical compositions and
      enzymatic saccharification of rice straw.
AB  - The effects of sodium carbonate (Na(2)CO(3)) pretreatment on the chemical
      compositions and enzymatic saccharification of rice straw were investigated. The
      enzymatic digestibility of rice straw is enhanced after pretreatment since
      pretreated solids show significant delignification with high sugar availability.
      During pretreatment, an increasing temperature and Na(2)CO(3) charge leads to
      enhanced delignification, whereas an increased degradation of polysaccharides as
      well, of which xylan acts more susceptible than glucan. The sugar recovery of
      enzymatic hydrolysis goes up rapidly with the total titratable alkali (TTA)
      increasing from 0% to 8%, and then it reaches a plateau. The highest sugar
      recovery of rice straw after pretreatment, 71.7%, 73.2%, and 76.1% for total
      sugar, glucan, and xylan, respectively, is obtained at 140 degrees C, TTA 8% and
      cellulase loading of 20 FPU/g-cellulose. In this condition, the corresponding
      delignification ratio of pretreated solid is 41.8%, while 95% of glucan and 76%
      of xylan are conserved.

PMID- 22989657
TI  - Green liquor pretreatment for improving enzymatic hydrolysis of corn stover.
AB  - Green liquor consists of sodium carbonate and sodium sulfide and is readily
      available in any kraft mills. The green liquor pretreatment process for
      bioethanol production was developed for wood chips. This process uses only proven
      technology and equipment currently used in a kraft pulp mill and has several
      additional advantages such as high sugar recovery and concentration, no
      inhibitive substances produced, as compared to acid-based pretreatment methods.
      The liquor was used to pretreat corn stover for enhancing enzymatic hydrolysis in
      bioethanol production. Pulp yield of 70% with 45% lignin removal was achieved
      under optimized conditions (8% total titratable alkali, 40% sulfidity and 140
      degrees C). About 70% of the original polysaccharides were converted into
      fermentable sugars, using 20 FPU/g-pulp of enzyme in the subsequent enzymatic
      hydrolysis. The result indicates that green liquor is a feasible pretreatment to
      improve the enzymatic saccharification of corn stover for bioethanol production.

PMID- 22989658
TI  - Pretreatment of wheat straw using SO2 dissolved in hot water.
AB  - Efficient pretreatment is important for complete enzymatic conversion of
      lignocellulosic materials. Pretreatment of wheat straw with sulfur dioxide
      (SO(2)) dissolved in hot water achieved xylose and total product yields of up to
      61.1% and 93.9%, respectively, based on the mass of lignocellulose in wheat
      straw. The apparent activation energies for hemicellulose conversion and xylose
      dehydration were 7.8 and 9.0 kJ/mol. FT-IR spectra of the residual solid after
      treatment showed that the hemicellulosic components were converted, the hydrogen
      bonds in cellulose were broken, but the lignin structure was not changed.
      Importantly, the SO(2) was recovered from the product mixture by steam stripping
      and could be reused. Thus, the SO(2)-H(2)O system is an efficient and
      environmentally friendly way for the conversion of hemicellulose in wheat straw
      into monosaccharides, such as xylose, glucose and arabinose.

PMID- 22989659
TI  - Selection and optimisation of a method for efficient metabolites extraction from
      microalgae.
AB  - Over the last decade, the use of microalgae for biofuel production and carbon
      dioxide sequestration has become a challenge worldwide. Processing costs are
      still too high for these methods to be profitable though, leading to a need to
      find high value by-products to optimise the added value of this biomass. For high
      throughput screening of such metabolites, it is essential to reach the inner
      content of the cell. This paper presents research and development of a technique
      enabling a high extraction yield of any metabolite, taking into account the
      difficulty of extracting bound and or inaccessible molecules with a wide variety
      of polarities. To this end, several disruption techniques were tested at
      laboratory scale on two biological models: Porphyridium purpureum and
      Phaeodactylum tricornutum. A mixer mill gave the best results, offering access to
      a broad diversity of metabolites from microalgae for high-throughput screening.

PMID- 22989660
TI  - Thermo- and mesophilic anaerobic digestion of wheat straw by the upflow anaerobic
      solid-state (UASS) process.
AB  - In this experimental work, the feasibility of wheat straw as a feedstock for
      biogas production is investigated using the newly developed upflow anaerobic
      solid-state (UASS) process. With the analytical emphasis placed on methane and
      metabolite production, both mesophilic and thermophilic 39 L UASS reactors were
      operated for 218 days at an organic loading rate of 2.5 g(VS)L(-1)d(-1) using
      wheat straw as sole substrate. For improved methanization of soluble metabolites,
      each UASS reactor was connected to an individual 30 L anaerobic filter (AF).
      During steady state thermophilic straw digestion was found to have a 36% higher
      methane yield (0.165 L g(VS)(-1)) whereas the hydrolysis rate constant increased
      by 106% (0.066 d(-1)).

PMID- 22989661
TI  - Anaerobic co-digestion of excess brewery yeast in a granular biomass reactor to
      enhance the production of biomethane.
AB  - The anaerobic co-digestion of brewery yeast using granular biomass was studied on
      the lab, pilot and full-scale. The study shows no adverse effects in the co
      digestion of yeast and wastewater in concentrations up to 1.1 (v/v)%. In
      concentrations up to 2.3% the process is manageable; however, not advisable. In
      concentrations over 2.8% the process exhibits failure due to the overload with
      suspended solids. An average specific biogas production of 0.560 m(3)kg(-1) of
      volatile solids was achieved. Full-scale operation with 0.7% yeast concentration
      showed a 38.5% increase in the biogas production and a 26.2% increase in the
      organic loading rate, which resulted in an increase of the biomethane/natural-gas
      substitute ratio from 10% to 16%. The influence of the yeast addition on the
      structure of the microbial biomass showed up to 7% dissimilarity in the archaeal
      and a 32% dissimilarity in the bacterial biomass community, which did not present
      any difficulties.

PMID- 22989662
TI  - Visual outcomes in corneal transplantation.

PMID- 22989663
TI  - Repeatability of measurements of effectiveness of glaucoma medication.
AB  - AIMS: To determine short-term repeatability of the effect of intraocular pressure
      (IOP) reducing medication and the number of repeated measurements necessary to
      estimate therapeutic effect with a given degree of precision. METHODS: IOP was
      measured at 8:00, 11:00 and 16:00 h at each of three weekly visits in untreated
      patients with primary open-angle glaucoma or ocular hypertension. After starting
      travaprost (0.004%) to both eyes, the measurements were repeated for a further
      three weekly visits. Repeatability of the change in IOP 1, 2 and 3 weeks after
      starting treatment was reported as the coefficient of repeatability (CR) and
      coefficient of variability (CV). RESULTS: Mean reduction in IOP was 7.5 mm Hg
      (29.9%). CR and CV between visits were 7.8 mm Hg and 37.2%, respectively.
      Repeated estimates of the effectiveness of treatment in the same subject at the
      same time of day would, therefore, be expected to lie within a range of 7.8 mm Hg
      and within +/-73.2% of the mean effect with 95% confidence. A reduction in IOP
      less than 7.8 mm Hg over a single pair of measurements would be indistinguishable
      from measurement error. Precision improves from +/-73.2% for a single pair of
      readings to +/-25.9% for eight pairs. CONCLUSIONS: Day-to-day repeatability in
      the estimation of medication effectiveness is poor even for time-of-day
      standardised measurements and the number of IOP measurements required to achieve
      precision adequate for use in clinical practice is large.

PMID- 22989664
TI  - EORTC 24051: unexpected side effects in a phase I study of TPF induction
      chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2
      inhibitor, in patients with locally advanced resectable larynx and hypopharynx
      squamous cell carcinoma.
AB  - BACKGROUND: In this phase I/II study, the addition of lapatinib (LAP) was
      investigated in combination with the sequential use of both approaches TPF
      induction chemotherapy (ICT) followed by chemoradiation (CRT) in locally advanced
      larynx or hypopharynx squamous cell carcinoma. PATIENTS AND METHODS: Objectives
      were to assess maximum tolerated dose, dose-limiting toxicity (DLT) and to
      recommend a safe dose of LAP when administered with 4 cycles of TPF followed by
      CRT. RESULTS: Seven male patients were included. Three patients were included in
      the first cohort, at dose level 1 (LAP 500 mg daily plus TPF). Renal toxicity was
      observed among these three patients (grade 3 [n=1], grade 2 [n=1] and grade 1
      [n=1]), with 1 DLT, leading to treatment interruption in this group.
      Nephrotoxicity was reversible after stopping LAP and hydration of the patients.
      In a second cohort of four patients administering docetaxel from the second
      cycle, 3 more DLTs were observed (grade 2 renal toxicity and grade 3 diarrhea,
      grade 3 anorexia and grade 3 stomatitis, and grade 4 neutropenia). Based on the
      occurrence of 4 DLTs at the first dose level of LAP, patient recruitment was
      closed. CONCLUSION: These data indicate that LAP cannot be combined safely with
      full dose TPF.

PMID- 22989666
TI  - Reply to Drs. Silva and Santana's letter.

PMID- 22989665
TI  - Malaria outside the Amazon region: natural Plasmodium infection in anophelines
      collected near an indigenous village in the Vale do Rio Branco, Itanhaem, SP,
      Brazil.
AB  - A few cases of Plasmodium vivax malaria in which anophelines of subgenus
      Kerteszia were incriminated as vectors have been reported outside the Amazon
      region, in the Atlantic Forest. This study was carried out near an indigenous
      Guarani village in the Curucutu reserve, an environmental protection area in the
      municipality of Itanhaem in the state of Sao Paulo, Brazil, on November 30, 2009,
      February 18, 2010, April 29, 2010 and May 26, 2010. Mosquitoes were collected
      along the route to the Guarani village where the edge of the Branco river
      floodplain meets the forests on the mountain slopes. Adult forms were collected
      with CO(2)-baited CDC traps and Shannon traps from twilight to 10:00 P.M.
      Anopheles cruzii predominated in both traps. The other species collected in the
      CDC traps were An. pseudomaculipes/maculipes, An. fluminensis and An.
      mediopunctatus/forattinii/costai. In addition to the latter three species, An.
      apicimacula/intermedius and An. strodei were also found in the Shannon traps. All
      but An. cruzii and An. strodei belong to subgenus Anopheles. A total of 506
      mosquitoes were assayed by PCR to detect natural infection by Plasmodium species.
      In the CDC traps, An. fluminensis and An. pseudomaculipes/maculipes were positive
      for Plasmodium malariae, while in the Shannon traps An. pseudomaculipes/maculipes
      was positive for Plasmodium vivax and Plasmodium malariae and An. cruzii was
      positive for P. malariae, resulting in a minimum infection rate of 0.24%. Our
      findings suggest that An. cruzii may be incriminated in the transmission of
      malaria between monkeys and humans, as this species was found to be infected by
      P. malariae. They also highlight the need for an understanding of the role of
      anophelines from outside subgenus Kerteszia in the transmission of malaria in the
      Atlantic Forest, as these were also found to be naturally infected by P. vivax
      and P. malariae.

PMID- 22989667
TI  - Acquired generalized hypertrichosis due to diazoxide.

PMID- 22989668
TI  - Detection of local recurrence following breast-conserving treatment in young
      women with early breast cancer: optimization of long-term follow-up strategies.
AB  - The detection of a local recurrence (LR) in young women with breast cancer after
      breast-conserving treatment (BCT) was investigated to compare the impact of
      different long-term follow-up strategies. Between 1988 and 2005, 937 women aged
      <=40 years were treated with BCT for early-stage breast cancer in the southern
      part of the Netherlands. Up to October 2009, 152 had developed an isolated LR.
      Information on follow-up visits was available for 124 of them. Fifty-four LRs
      (44%) were diagnosed within 5 years and 70 (56%) more than 5 years after BCT.
      Fifty-six LRs (45%) were detected during routine follow-up visits and 68 (55%)
      presented between two visits. Sixty-six LRs (53%) were diagnosed in patients
      reporting symptoms. In 31 patients (25%) the LR was found by mammography alone.
      About a quarter of the LRs was larger than 2 cm in diameter. These results imply
      that current follow-up strategies for young women with BCT do not guarantee a
      timely detection of LR.

PMID- 22989669
TI  - Morphological and molecular analyses of larval trematodes in the intertidal
      bivalve Perumytilus purpuratus from central Chile.
AB  - The bivalve Perumytilus purpuratus is a common species that is widely distributed
      throughout rocky intertidal zones in Chile. This bivalve is the first
      intermediate host for three trematode species: one bucephalid (an undetermined
      species) and two fellodistomids (Proctoeces lintoni and one undetermined
      species). A few studies based on morphological comparisons, experimental
      infection and molecular analyses have been performed to ascertain the taxon (at
      least at the family level) to which these trematodes belong; yet, there remains
      no clarification about the specific identity of these trematodes. Therefore, in
      this study, we compared the V4 region nucleotide sequences of the 18S rRNA of
      these three sporocyst species, classified as morphotypes, found in P. purpuratus
      and nine adult trematode species from intertidal fishes that are likely
      definitive hosts for these parasites. The sequences from two of the sporocyst
      morphotypes matched with adult trematodes from the intertidal fish: type 1
      sporocyst was similar to Prosorhynchoides carvajali (Bucephalidae), with a mean
      genetic divergence of 0.78%, and type 2 sporocyst was similar to Proctoeces sp.
      (but not P. lintoni), with 0% genetic divergence. The third species (type 3
      sporocyst) was classified to the family Fellodistomidae; however, the sequence
      from this species differed greatly from the three other fellodistomid species
      documented in the marine fish of Chile and from other fellodistomids in public
      databases. Moreover, this morphotype has a particular cercarial morphology that
      greatly differs from other fellodistomid species described thus far. Therefore,
      this intriguing trematode remains a mystery. 

PMID- 22989670
TI  - Differential action of monohydroxylated polycyclic aromatic hydrocarbons with
      estrogen receptors alpha and beta.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a diverse group of widespread
      environmental pollutants, some of which have been found to be estrogenic or
      antiestrogenic. Recent data have shown that hydroxylated PAH metabolites may be
      responsible for the estrogenic effects of some PAHs. The purpose of this study
      was to investigate the effects of several PAHs, as well as their monohydroxylated
      metabolites, on estrogen receptors (ERs), ERalpha and ERbeta. Three parent PAHs
      and their monohydroxylated metabolites were each evaluated using transcriptional
      reporter assays in isogenic stable cell lines to measure receptor activation,
      competitive binding assays to determine ligand binding, and bioluminescence
      resonance energy transfer assays to assess dimerization. Finally, the estrogenic
      effects of the hydroxylated metabolites were confirmed by quantitative real-time
      PCR of estrogen-responsive target genes. Although the parent PAHs did not induce
      ERalpha or ERbeta transcriptional activity, all of the monohydroxylated PAHs (1
      OH naphthanol, 9-OH phenanthrene, 1-OH pyrene) selectively induced ERbeta
      transcriptional activity at the concentrations tested, while not activating
      ERalpha. Additionally, the monohydroxylated PAHs were able to competively bind
      ERbeta, induce ERbeta homodimers, and regulate ERbeta target genes. Although
      monohydroxylated PAHs appeared to have weak agonist activity to ERbeta, our
      results showed that they can elicit a biologically active response from ERbeta in
      human breast cancer cells and potentially interfere with ERbeta signaling
      pathways.

PMID- 22989671
TI  - Which specificity in cooperation between phytostimulating rhizobacteria and
      plants?
AB  - Plant growth-promoting rhizobacteria (PGPR) are found in association with a large
      range of host plants. Although the subject of plant host specificity has been
      well studied in parasitic and mutualistic interactions, the question of whether
      phytostimulating rhizobacteria efficiently interact only with a specific host
      remains poorly discussed. This review presents elements suggesting the existence
      of specificity in three-step establishment of associative symbiosis between
      phytostimulating rhizobacteria and plants: bacterial attraction by the host
      plant, bacterial colonization of roots, and functioning of associative symbiosis.

PMID- 22989672
TI  - Epifluorescent direct counts of bacteria and viruses from topsoil of various
      desert dust storm regions.
AB  - Topsoil from arid regions is the main source of dust clouds that move through the
      earth's atmosphere, and microbial communities within these soils can survive long
      range dispersion. Microbial abundance and chemical composition were analyzed in
      topsoil from various desert regions. Statistical analyses showed that microbial
      direct counts were strongly positively correlated with calcium concentrations and
      negatively correlated with silicon concentrations. While variance between deserts
      was expected, it was interesting to note differences between sample sites within
      a given desert region, illustrating the 'patchy' nature of microbial communities
      in desert environments.

PMID- 22989673
TI  - Impact of salinity-tolerant MCM6 transgenic tobacco on soil enzymatic activities
      and the functional diversity of rhizosphere microbial communities.
AB  - The development of genetically modified plants for agriculture has provided
      numerous economic benefits, but has also raised concern over the potential impact
      of transgenic plants upon the environment. The rhizosphere is the soil
      compartment that is directly under the influence of living roots; it constitutes
      a complex niche likely to be exploited by a wide variety of bacteria potentially
      influenced by the introduction of transgenes in genetically modified plants. In
      the present study, the impact of overexpression of the salinity stress-tolerant
      minichromosome maintenance complex subunit 6 (MCM6) gene upon functional
      diversity and soil enzymatic activity in the rhizosphere of transgenic tobacco in
      the presence and absence of salt stress was examined. The diversity of culturable
      bacterial communities and soil enzymes, namely, dehydrogenases and acid
      phosphatases, was assessed and revealed no significant (or only minor)
      alterations due to transgenes in the rhizosphere soil of tobacco plants. Patterns
      in principal components analysis showed clustering of transgenic and non
      transgenic tobacco plants according to the fingerprint of their associated
      bacterial communities. However, the presence of MCM6 tobacco did not cause
      changes in microbial populations, soil enzymatic activities or the functional
      diversity of the rhizosphere soil microbial community.

PMID- 22989674
TI  - [Immunological diseases of buccal localisation].

PMID- 22989675
TI  - [Human immunodeficiency virus/AIDS and immigration: an essential issue].

PMID- 22989676
TI  - [Hypertriglyceridemia-increased waist: may we improve the prediction of
      cardiovascular risk in human immunodeficiency virus infection?].

PMID- 22989677
TI  - [Acute glaucoma associated to topiramate: report of 2 cases].

PMID- 22989678
TI  - [New synthetic drugs: legal highs in Spain (2010-2012)].

PMID- 22989679
TI  - [Classic homocystinuria: rare cause of massive pulmonary thromboembolism with
      cardiac arrest].

PMID- 22989680
TI  - [Acral vasculitis and pancytopenia as a paraneoplastic syndrome associated with
      epidermoid lung cancer].

PMID- 22989681
TI  - [Recurrent pleural effusion and marked elevation of CA-125 in a patient with
      pseudo-Meigs' syndrome secondary to a struma ovarii].

PMID- 22989682
TI  - [Intermittent gastrointestinal bleeding secondary to small bowel cavernous
      hemangioma diagnosed by wireless capsule endoscopy].

PMID- 22989683
TI  - [Inhospital cardio-cerebral resuscitation].

PMID- 22989684
TI  - [Dysphonia as non-local tumour expression].

PMID- 22989685
TI  - Activation of nicotinic acetylcholine receptors on bone marrow-derived cells
      relieves neuropathic pain accompanied by peripheral neuroinflammation.
AB  - Emerging evidence indicates that chronic neuroinflammation plays a pivotal role
      in neuropathic pain. We explored whether activation of the nicotinic
      acetylcholine receptor (nAChRs) pathway on peripheral immune cells improves
      neuropathic pain. Mice were subjected to partial sciatic nerve ligation (PSL).
      Enhanced green fluorescent protein (EGFP)-chimeric mice were generated by
      transplantation of EGFP(+) bone marrow (BM) cells from EGFP-transgenic mice into
      wild-type mice. EGFP(+) BM-derived cells infiltrated the injured sciatic nerve
      (SCN) of EGFP-chimeric mice, and these cells were found to be F4/80(+)
      macrophages and Ly6G(+) neutrophils. The protein expression of nAChR subunit
      alpha4 and alpha7 were up-regulated in the injured SCN. Increased alpha4 and
      alpha7 subunits were localized on both BM-derived macrophages and neutrophils.
      When nicotine (20nmol) was perineurally administered once a day for 4days (days 0
      3), PSL-induced tactile allodynia and thermal hyperalgesia were significantly
      prevented. Relieving effects of nicotine on neuropathic pain were reversed by co
      administration of mecamylamine (20nmol), a non-selective antagonist for nAChRs.
      PSL-induced up-regulation of inflammatory cytokines and chemokines was suppressed
      by perineural administration of nicotine. Taken together, the expression of
      alpha4beta2 and alpha7 subtypes of nAChRs may be increased on circulating
      macrophages and neutrophils in injured peripheral nerves. Activation of nAChRs on
      immune cells may relieve neuropathic pain accompanied by the suppression of
      neuroinflammation.

PMID- 22989686
TI  - Conducting vaccine clinical trials in sub-Saharan Africa: operational challenges
      and lessons learned from the Meningitis Vaccine Project.
AB  - Group A Neisseria meningitidis epidemics have been an important and unresolved
      public health problem in sub-Saharan Africa for over a century. The Meningitis
      Vaccine Project (MVP) was established in 2001 with the goal of developing,
      testing, licensing, and introducing an affordable group A meningococcal conjugate
      vaccine for Africa. A monovalent group A conjugate vaccine, MenAfriVacTM, was
      developed at the Serum Institute of India Ltd. and tested in clinical trials at
      multiple trial sites in sub-Saharan African countries. The setup and successful
      conduct of ICH-GCP standard vaccine trials across multiple trial sites located in
      low-resource settings are challenging. We describe the main operational issues
      encountered in three randomized, observer-blind, active controlled studies to
      evaluate the safety and immunogenicity of MenAfriVacTM. The studies were
      conducted in parallel among 2700 subjects aged between 2 months and 29 years of
      age enrolled across four trial sites located in Mali, The Gambia, Senegal, and
      Ghana between September 2006 and August 2009. Many important lessons were learned
      during the preparation, setup, and implementation of the Meningitis Vaccine
      Project clinical program. They are summarized here to help vaccine development
      programs identify efficient pathways for successful implementation of clinical
      trials in low-resource settings.

PMID- 22989687
TI  - An HIVgp41 vaccine protects CD4 central memory T cells in SHIV-infected macaques.
AB  - BACKGROUND: The immunodeficiency defining AIDS results from a progressive decline
      in the number of CD4(+) T cells. Although no single viral protein is likely to be
      the sole effector of immune impairment, the gp41 envelope protein is believed to
      contribute significantly to AIDS pathogenesis. We have shown that 3S, a unique
      motif of gp41, is highly conserved in HIV-1 strains and specifically induces
      NKp44L, a ligand of the natural cytotoxicity receptor NKp44, on CD4(+) T cells,
      rendering them sensitive to NK lysis. We therefore hypothesized that a 3S/gp41
      vaccine strategy designed to modulate the NK cell compartment might improve
      CD4(+) T cell resistance, independently of any effect on viral load. METHODS:
      Nine macaques were chronically infected with the SHIV163P3; four were then
      immunized with the 3S/gp41 peptide and five with the carrier alone. Frequency of
      CD4(+) T cell subsets, proliferation, cell activation and apoptosis were analyzed
      in the periphery and the lymph nodes, spleen and rectum by flow cytometry.
      RESULTS: The anti-3S antibodies prevented NKp44L expression on CD4(+) T cells in
      vivo and subsequently preserved the CD4(+) central memory T cells in 3S/gp41
      vaccinated animals. They also limited the NK cytotoxic activity against
      autologous CD4(+) T cells, the cell activation, the proliferation, and the
      apoptosis in peripheral blood and secondary lymphoid tissues remained intact.
      CONCLUSION: These data suggest a new paradigm for AIDS vaccine development, aimed
      at generating specific responses to protect a specific subset of CD4(+) T cells
      from attack by activated NK cells.

PMID- 22989688
TI  - Implementation of a hepatitis A/B vaccination program using an accelerated
      schedule among high-risk inmates, Los Angeles County Jail, 2007-2010.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommend vaccination
      for men who have sex with men (MSM) and injection drug users against hepatitis A
      and B. This study is the first report of a hepatitis vaccination program in a
      United States jail with a combined vaccine using an accelerated schedule. Los
      Angeles County has the largest jail system in the nation and Men's Central Jail
      (MCJ) is the largest facility within that system. MCJ includes a unit for self
      identified MSM, where approximately 2700 inmates are housed per year. METHODS AND
      FINDINGS: Starting in August 2007, a combined hepatitis A and B vaccine was
      offered to all inmates housed in this special unit. Using an accelerated schedule
      (0-, 7-, 21-30 days, 12-month booster), a total of 3931 doses were administered
      to 1633 inmates as of June 2010. Of those, 77% received 2 doses, 58% received 3
      doses, and 11% received the booster dose. Inmates who screened positive for a
      sexually transmitted infection in this unit were 1.3 times more likely to be
      vaccinated (95% CI 1.2-1.4) compared to others in the same housing unit who
      screened negative. CONCLUSIONS: Hepatitis vaccination initiatives can be
      successfully implemented in an urban jail among an extremely high-risk population
      using the accelerated, combined hepatitis A/B vaccine. Ours may be a useful model
      for other programs to vaccinate incarcerated populations.

PMID- 22989689
TI  - Nanoemulsion W805EC improves immune responses upon intranasal delivery of an
      inactivated pandemic H1N1 influenza vaccine.
AB  - Currently available influenza vaccines provide suboptimal protection. In order to
      improve the quality of protective immune responses elicited following
      vaccination, we developed an oil-in-water nanoemulsion (NE)-based adjuvant for an
      intranasally-delivered inactivated influenza vaccine. Using a prime-boost
      vaccination regimen, we show that intranasal vaccines containing the W(80)5EC NE
      elicited higher titers of serum hemagglutination inhibiting (HAI) antibody and
      influenza-specific IgG and IgA titers compared to vaccines that did not contain
      the NE. Similarly, vaccines containing the W(80)5EC NE resulted in higher
      influenza-specific IgA levels in the bronchoalveolar lavage (BAL) fluid and nasal
      wash when compared to vaccines formulated without NE. The higher antibody titers
      in mice immunized with the NE-containing vaccines correlated with reduced viral
      loads in the lungs and nasal turbinates following a high dose viral challenge.
      Mice immunized with vaccines containing the W(80)5EC NE also showed a reduction
      in body weight loss following challenge compared to mice immunized with
      equivalent vaccines produced without NE. Taken together, our results show that
      the W(80)5EC NE substantially improves the magnitude of protective influenza
      specific antibody responses and is a promising mucosal adjuvant for influenza
      vaccines and vaccines against other mucosal pathogens.

PMID- 22989690
TI  - Pandemic whole-virion, Vero-cell-derived, adjuvant-free influenza A H1N1 vaccine
      in patients with solid tumors and hematologic malignancies receiving concurrent
      anticancer treatment: Immunogenicity, tolerability, and acceptability during the
      pandemic situation.
AB  - Patients with malignancies are considered to be at increased risk of acquiring
      influenza. Because of higher complication and case fatality rates, preventive
      measures such as vaccination are of great interest. The objective of this study
      was to assess the acceptability, tolerability and immunogenicity of an adjuvant
      free whole-virion pandemic influenza A (H1N1) vaccine in cancer patients with
      ongoing anticancer treatment during a 'pandemic situation'. Adult patients with
      hematologic malignancies or solid tumors and concurrent cytotoxic, targeted,
      and/or hormone therapy were recruited during the influenza A (H1N1) pandemic in
      2009/2010 and were offered free vaccine. Antibody titers were measured using
      virus-specific hemagglutination inhibition assay and ELISA. Among 285 patients
      with solid tumors who were offered vaccination during their therapy, 260 (91.2%)
      declined and 25 (8.8%) accepted. Seventeen patients with hematologic malignancies
      were also vaccinated during therapy; 23 healthy individuals served as a control
      group. When measured using hemagglutination-inhibition assays, rates of
      seroprotection, seroconversion, and geometric mean titer ratios after the second
      vaccination were 96%, 70%, and 4.1 respectively among the healthy individuals,
      90%, 52%, and 4.3 among patients with solid tumors, and 67%, 13%, and 1.5 among
      patients with hematologic malignancies during therapy (P<0.05). When measured
      using ELISA, seropositivity differed significantly among the three groups after
      the second vaccination: healthy individuals 74%, patients with solid tumors 57%,
      those with hematologic malignancies 13% (P<0.001). The vaccine was well
      tolerated. Our results demonstrate a low uptake of the well tolerated adjuvant
      free influenza A (H1N1) vaccine by cancer patients receiving anticancer treatment
      during the pandemic of 2009/2010. Among the vaccinated patients, the immune
      response was weaker than that in healthy individuals. The immune response in
      patients with hematological malignancies was low. Two doses of vaccine are needed
      in these immunosuppressed patients.

PMID- 22989691
TI  - An escape from agony: a qualitative psychological autopsy study of women's
      suicide in a post-conflict northern Uganda.
AB  - We set out to investigate suicide among women in a post-conflict context in
      Northern Uganda using qualitative psychological autopsy interviews. Three to five
      relatives and friends for each of the three suicides recruited were interviewed
      (N=11). Through interpretative phenomenological analysis (IPA) we found that the
      women all had been through traumatic experiences attributable to the protracted
      war/conflict between the rebel groups and Ugandan Government armed forces.
      Nevertheless, the decision of self-inflicted death seemed to have been due to a
      combination of unpleasant experiences/events that prevailed within the last 3
      months prior to the suicide. These experiences are summarized in two broad
      themes: No control in life and No care. Changes in the traditional gender roles,
      men's quest for their lost masculinity, and women's attempt to fight for their
      rights that was perceived as a cultural transgression contributed to the women's
      suicides.

PMID- 22989692
TI  - Correlation of infused CD3+CD8+ cells with single-donor dominance after double
      unit cord blood transplantation.
AB  - Single-donor dominance is observed in the majority of patients following double
      unit cord blood transplantation (dCBT); however, the biological basis for this
      outcome is poorly understood. To investigate the possible influence of specific
      cell lineages on dominance in dCBT, flow cytometry assessment for CD34(+),
      CD14(+), CD20(+), CD3(-)CD56(+), CD3(+)CD56(+) (natural killer), and T cell
      subsets (CD4(+), CD8(+), memory, naive, and regulatory) was performed on
      individual units. Subsets were calculated as infused viable cells per kilogram of
      recipient actual weight. Sixty patients who underwent dCBT were included in the
      final analysis. Higher CD3(+) cell dose was statistically concordant with the
      dominant unit in 72% of cases (P = .0006). Further T cell subset analyses showed
      that dominance was correlated more with the naive CD8(+) cell subset (71%
      concordance; P = .009) than with the naive CD4(+) cell subset (61% concordance; P
      = .19). These data indicate that a greater total CD3(+) cell dose, particularly
      of naive CD3(+)CD8(+) T cells, may play an important role in determining single
      donor dominance after dCBT.

PMID- 22989693
TI  - Lemierre syndrome secondary to community-acquired methicillin-resistant
      Staphylococcus aureus infection associated with cavernous sinus thromboses.
AB  - BACKGROUND: Lemierre Syndrome (LS) is a highly aggressive rare disease process
      with a predilection for young, healthy adolescents. Often beginning with a
      primary cervicofacial infection, LS rapidly progresses to thrombophlebitis of the
      cerebral vasculature, metastatic infection, and septicemia. Untreated LS can be
      rapidly fatal. Thrombus within the cerebral vasculature can have devastating
      neurological effects. Advances in antibacterial therapy have resulted in a global
      decline in the incidence of LS, and clinicians may not consider LS early in the
      disease process. Although the mortality of LS has declined, the morbidity
      associated with the disease has increased, particularly the neurological
      sequelae. OBJECTIVES: This report will provide readers with a better
      understanding of the etiology, clinical presentation, evaluation methods, and
      appropriate treatment of LS. CASE REPORT: We present an atypical case of LS
      secondary to community-acquired methicillin-resistant Staphylococcus aureus
      (MRSA) infection progressing to bilateral cavernous sinus and ophthalmic vein
      thromboses with resultant binocular vision loss secondary to optic nerve and
      retinal ischemia. CONCLUSION: This case highlights the importance of early
      recognition of LS in the setting of a community-acquired MRSA infection as the
      unifying condition in a young patient with multiple acute neurologic impairments.

PMID- 22989694
TI  - Flash pulmonary edema in multiple sclerosis.
AB  - BACKGROUND: Neurogenic pulmonary edema (NPE) occurs in the setting of an acute
      neurological insult and in the absence of a primary cardiopulmonary cause. No
      unifying theory on NPE pathogenesis exists. NPE triggered by a discrete
      neurological lesion is rare, but such cases offer valuable insight into NPE
      pathogenesis. OBJECTIVE: To describe an unusual and instructive case of NPE in
      multiple sclerosis. CASE REPORT: A young woman with multiple sclerosis presented
      to the Emergency Department in acute respiratory failure. She was cyanotic
      centrally, hypertensive, and tachycardic. The chest X-ray study suggested
      pulmonary edema. She required non-invasive mechanical ventilation for 12 h.
      Echocardiography revealed left ventricular hypokinesis. The asymmetrical
      pulmonary infiltrate raised the suspicion of pneumonia; she was given intravenous
      antibiotics. By 36 h, she had persistent dyspnea, paroxysmal tachycardia, nausea,
      and facial flushing; carcinoid syndrome was excluded. By 48 h, she had facial
      numbness and ataxia. Magnetic resonance imaging (MRI) revealed a demyelinating
      lesion at the rostromedial medulla. Her symptoms promptly resolved with
      intravenous steroids, as did the perilesional edema on follow-up MRI. CONCLUSION:
      Life-threatening pulmonary edema can complicate medullary demyelination. Lack of
      awareness of this diagnostic possibility and an asymmetrical pulmonary infiltrate
      culminated in diagnostic delay in this case. The case provides clinico
      radiological evidence of the pathogenic link between medullary lesions and NPE.
      The pathogenesis is likely to rely on lesion involvement of the nucleus tractus
      solitarius or its immediate pathways. Non-uniform vasoconstriction of the
      pulmonary arterial bed might account for the other peculiarity of this case: the
      asymmetrical pulmonary infiltrate. Timely diagnosis of NPE is essential because
      the condition is best managed by nullifying the "neurogenic" trigger.

PMID- 22989695
TI  - Synthetic cannabinoid intoxication: a case series and review.
AB  - BACKGROUND: Synthetic cannabinoid receptor agonists are becoming increasingly
      popular with adolescents as an abused substance. Chronic use of these drugs can
      lead to addiction syndrome and withdrawal symptoms similar to cannabis abuse. Due
      to their potential health risk, several countries have banned these substances.
      OBJECTIVES: To report the clinical presentation and legislation status of
      synthetic cannabinoids in "Spice" products and alert the health care community
      about the identification and risk assessment problems of these compounds. CASE
      REPORTS: We retrospectively reviewed cases presenting to our Emergency Department
      (ED) during a 3-month period with chief complaints of Spice drug use before
      arrival. Six cases presented to our ED after using Spice drugs. Two patients were
      admitted after reporting seizures. All but one presented with tachycardia. Two
      patients had hallucinations. The average length of ED observation was 2.8 h. No
      patient with seizures had recurrent episodes. CONCLUSION: Spice drugs can cause
      potentially serious health care conditions that necessitate ED evaluation. Most
      cases can be discharged from the ED after a period of observation. Legal issues
      surrounding these drugs are yet to be finalized in the United States.

PMID- 22989696
TI  - Unusual case of foreign-body ingestion.

PMID- 22989697
TI  - Emergency department team communication with the patient: the patient's
      perspective.
AB  - BACKGROUND: Effective communication is important for the delivery of quality
      care. The Emergency Department (ED) environment poses significant challenges to
      effective communication. OBJECTIVES: The objective of this study was to determine
      patients' perceptions of their ED team's communication skills. METHODS: This was
      a cross-sectional study in an urban, academic ED. Patients completed the
      Communication Assessment Tool for Teams (CAT-T) survey upon ED exit. The CAT-T
      was adapted from the psychometrically validated Communication Assessment Tool
      (CAT) to measure patient perceptions of communication with a medical team. The 14
      core CAT-T items are associated with a 5-point scale (5 = excellent); results are
      reported as the percent of participants who responded "excellent." Responses were
      analyzed for differences based on age, sex, race, and operational metrics (wait
      time, ED daily census). RESULTS: There were 346 patients identified; the final
      sample for analysis was 226 patients (53.5% female, 48.2% Caucasian),
      representing a response rate of 65.3%. The scores on CAT-T items (reported as %
      "excellent") ranged from 50.0% to 76.1%. The highest-scoring items were "let me
      talk without interruptions" (76.1%), "talked in terms I could understand"
      (75.2%), and "treated me with respect" (74.3%). The lowest-scoring item was
      "encouraged me to ask questions" (50.0%). No differences were noted based on
      patient sex, race, age, wait time, or daily census of the ED. CONCLUSIONS: The
      patients in this study perceived that the ED teams were respectful and allowed
      them to talk without interruptions; however, lower ratings were given for items
      related to actively engaging the patient in decision-making and asking questions.

PMID- 22989698
TI  - Colorectal perforation by self-induced hydrostatic pressure: a report of two
      cases.
AB  - BACKGROUND: Most iatrogenic colorectal perforations occur as a result of
      endoscopic or fluoroscopic studies. Accidents associated with hydrostatic
      pressure-induced perforation are rarely reported, and self-induced hydrostatic
      pressure is an extremely rare cause of perforation because the anal sphincter
      complex may provide a protective barrier against perianal hydrostatic pressure.
      We present two cases of rectosigmoid colon perforation secondary to self-induced
      hydrostatic pressure. CASE REPORTS: A 61-year-old man and a 45-year-old man
      presented with abdominal pain after forceful entry of tap water into the rectum,
      during rinsing of the anus after defecation in the first case, and during self
      administered enema in the second case. Emergency operations were performed with
      the suspicion of hydrostatic pressure-induced rectal injury, and showed
      rectosigmoid mesenteric perforation in both cases. Resection of the diseased
      segment and end colostomy (Hartmann's procedure) was performed in the first case,
      and primary resection and anastomosis in the second case. The pathologic results
      showed abrupt loss of the colonic wall in the mesenteric border, without evidence
      of other inflammatory disease; these findings were consistent with acute
      mechanical colon injury. The postoperative course in both cases was uneventful.
      CONCLUSION: These cases put forth an unusual type of colorectal injury, caused
      specifically by hydrostatic pressure, thus adding to the available literature on
      hydrostatic pressure-induced injury.

PMID- 22989699
TI  - Long distance root-shoot signalling in plant-insect community interactions.
AB  - Plants mediate interactions between insects, including leaf- and root-feeders;
      yet the underlying mechanisms and connection with ecological theory remain
      unresolved. In this review, based on novel insights into long-distance (i.e.,
      leaf-leaf, root-shoot) defence signalling, we explore the role of phytohormones
      in driving broad-scale patterns of aboveground-belowground interactions that can
      be extrapolated to general plant-insect relationships. We propose that the
      outcome of intra-feeding guild interactions is generally negative due to
      induction of similar phytohormonal pathways, whereas between-guild interactions
      are often positive due to negative signal crosstalk. However, not all outcomes
      could be explained by feeding guild; we argue that future studies should target
      ecologically representative plant-insect systems, distinguish subguilds, and
      include plant growth hormones to improve our understanding of plant-mediated
      interactions.

PMID- 22989700
TI  - The Boston Rehabilitative Impairment Study of the Elderly: a description of
      methods.
AB  - OBJECTIVES: To describe the methods of a longitudinal cohort study among older
      adults with preclinical disability. The study aims to address the lack of
      evidence guiding mobility rehabilitation for older adults by identifying those
      impairments and impairment combinations that are most responsible for mobility
      decline and disability progression over 2 years of follow-up. DESIGN:
      Longitudinal cohort study. SETTING: Metropolitan-based health care system.
      PARTICIPANTS: Community-dwelling primary care patients aged >=65 years (N=430),
      with self-reported modification of mobility tasks because of underlying health
      conditions. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Late Life
      Function and Disability Instrument (LLFDI) (primary outcome); Short Physical
      Performance Battery and 400-m walk test (secondary outcomes). RESULTS: Among 7403
      primary care patients identified as being potentially eligible for participation,
      430 were enrolled. Participants have a mean age of 76.5 years, are 68% women, and
      have on average 4.2 chronic conditions. Mean LLFDI scores are 55.5 for Function
      and 68.9 and 52.3 for the Disability Limitation and Frequency domains,
      respectively. CONCLUSIONS: Completion of our study aims will inform development
      of primary care-based rehabilitative strategies to prevent disability.
      Additionally, data generated in this investigation can also serve as a vital
      resource for ancillary studies addressing important questions in rehabilitative
      science relevant to geriatric care.

PMID- 22989701
TI  - Acute subdural hematoma following halo pin tightening in a patient with bilateral
      vertebral artery dissection.
AB  - We report the first case of acute subdural hematoma (SDH) developing after
      tightening the halo of an osteoporotic 61-year-old woman on warfarin therapy for
      bilateral traumatic vertebral artery dissection. We discuss literature relevant
      to this case with an emphasis on identifying warning signs, including recurrent
      pin loosening, especially in patients with compromised bone structure and high
      risk of bleeding. Our 61-year-old patient presented to neurosurgery clinic for a
      2-month follow-up of a type-III odontoid fracture sustained in a motor vehicle
      accident. The patient had repeatedly loosened halo pins, and shortly after the
      pins were tightened, the patient had a syncopal event and struck her head. An
      emergent computed tomography scan revealed acute SDH requiring emergent
      craniotomy and evacuation. SDH following pin penetration in a patient with
      bilateral vertebral artery dissection, osteoporosis, and anticoagulation has not
      been reported as a complication of the use of the halo vest for stabilization of
      the cervical spine. The risk of this serious complication can be minimized by
      giving special consideration to patients with comorbidities and by repositioning
      problematic pins. This case demonstrates the importance of special attention to
      bone strength, bleeding risk, and recurrent minor complaints with use of the halo
      vest.

PMID- 22989702
TI  - Growth inhibition and induction of apoptosis in human cancerous HeLa cells by
      Maytenus procumbens.
AB  - The possible biochemical activities of the acetonic/ethanolic extract of the
      leaves of Maytenus procumbens (L.M.P), and its isolated compounds were
      investigated in the present study. In cytotoxicity assay, L.M.P showed IC(50) of
      68.79, 51.22, 78.49, 76.59, and 76.64MUg/ml on Caco-2, HeLa, HT29, NIH3T3, and
      T47D cells, respectively. Bioassay guided fractionation led to the isolation and
      identification of a new triterpene: '30-hydroxy-11alpha-methoxy-18beta-olean-12
      en-3-one' (HMO) in addition to a known terpenoid: 'asiatic acid' (AA). HMO
      exhibited the most cytotoxicity against HeLa cells and was further investigated
      for its ability to induce apoptosis in HeLa cells. HMO induced apoptosis up to
      20.41% in HeLa cells versus control group (0.40%). Antioxidant/oxidative
      properties of L.M.P and HMO were investigated using extracellular (DPPH), and
      intracellular (ROS) assays. Experimental samples represented a time and
      concentration-dependent formation of ROS in Hela cells. Generation of ROS seems
      one of the mechanisms by which HMO induces apoptosis in Hela cells. Conclusion is
      that the active components in L.M.P might serve as a mediator of the ROS
      scavenging system and have the potential to act as prooxidant or antioxidant
      depending on the biological environment of the cells.

PMID- 22989703
TI  - Comparative antioxidant effects of lycopene, apo-10'-lycopenoic acid and apo-14'
      lycopenoic acid in human macrophages exposed to H2O2 and cigarette smoke extract.
AB  - Much of the beneficial effects of tomato lycopene in the prevention of chronic
      diseases has been attributed to its antioxidant properties, which could be
      mediated by its metabolites and/or oxidation products. However, the biological
      functions of these lycopene derivatives remain still unknown. In the present
      study, we evaluated and compared the antioxidant efficacy of the lycopene
      eccentric cleavage products apo-10'-lycopenoic acid and apo-14'-lycopenoic acid
      in counteracting the oxidative effects of H(2)O(2) and cigarette smoke extract
      (CSE) in THP-1 macrophages. Both apo-10'-lycopenoic acid and apo-14'-lycopenoic
      acid were able to inhibit spontaneous and H(2)O(2)-induced ROS production in a
      dose-dependent manner. Such an effect was accompanied by an inhibition of MAPK
      phosphorylation, by NF-kappaB inactivation, and by inhibition of hsp-70 and hsp
      90 expressions. Both apo-lycopenoic acids also decreased CSE-induced ROS
      production, 8-OHdG formation and reduced the increase in NOX-4 and COX-2
      expressions caused by CSE. However, in both the models of oxidative stress, apo
      14'-lycopenoic acid was much more potent as an antioxidant than apo-10'
      lycopenoic acid, showing antioxidant properties similar to lycopene. These data
      strongly suggest that apo-lycopenoic acids, and particularly apo-14'-lycopenoic
      acid, may mediate some of the antioxidant functions of lycopene in cells.

PMID- 22989704
TI  - Efficacy of all-trans retinoid acid in preventing nickel induced cardiotoxicity
      in myocardial cells of rats.
AB  - Nickel, a metal commonly found in battery plants and welding factories, has
      potential cardiotoxicity, while all-trans retinoid acid (atRA) can promote
      cardiovascular repair and myocardial recovery. The purpose of this study was to
      investigate whether atRA could prevent cardiotoxicity induced by nickel both in
      vitro and in vivo. In the study, a rat myocardial cell line (H9c2) exposed to
      different concentrations of nickel chloride (NiCl(2)) displayed apoptotic
      features accompanied by reactive oxygen species generation. In addition, NiCl(2)
      also caused obvious apoptosis and systolic dysfunction in primary myocardial
      cells. Treatment with atRA efficiently attenuated the cytotoxicities triggered by
      NiCl(2) as it significantly mitigated ROS generation and decreased MAP kinases
      activity in NiCl(2)-treated cardiomyocytes. Additionally, NiCl(2) exposure caused
      obvious arrhythmia in Sprague-Dawley rats with the maximum tolerance dose of
      NiCl(2) between 2 and 3mg/kg. A combinational intragastric administration of
      40mg/kg atRA can partially reverse NiCl(2)-induced arrhythmia in rats. Our
      results suggested that atRA might have therapeutic potential in alleviating the
      adverse effects of nickel on the cardiovascular system.

PMID- 22989705
TI  - Pioglitazone protects against cisplatin induced nephrotoxicity in rats and
      potentiates its anticancer activity against human renal adenocarcinoma cell
      lines.
AB  - Cisplatin-induced nephrotoxicity is a serious problem that limits its use in
      cancer treatment. The present study aimed to investigate the renal protective
      capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The
      underlying suggested mechanism(s) and whether this nephroprotective effect (if
      any) interferes with the cytotoxic effect of cisplatin on cancer cells were also
      investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected
      (Peroxisome proliferator- activated receptor gamma (PPAR-gamma) antagonist), or
      their combination were administered to rats one hour before cisplatin injection.
      Moreover, their effects on the cell viability of human renal adenocarcinoma cell
      models (ACHN) were studied. The obtained results showed that pioglitazone
      improved the renal function, structural changes, renal malondialdehyde (MDA),
      tumor necrosis factor alpha (TNF-alpha), nuclear factor kappa B (NF-kappaB) genes
      expression in cisplatin injected rats. It increased both renal reduced
      glutathione (GSH) content and PPAR-gamma gene expression. In contrast to the data
      obtained by prior administration of BADGE. Pioglitazone also potentiated the
      cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect
      was abolished by BADGE co administration. In conclusion, these results suggested
      that pioglitazone protected against cisplatin- induced nephrotoxicity through its
      interaction with PPAR-gamma receptors and antioxidant effects. Furthermore,
      pioglitazone did not interfere but rather potentiated the cytotoxic effects of
      cisplatin on human renal adenocarcinoma cells.

PMID- 22989706
TI  - The relationship between nematode infections and ontogeny and diet of the lizard
      Tropidurus torquatus (Wied, 1820) (Squamata: Tropiduridae) from the Atlantic
      Rainforest in south-eastern Brazil.
AB  - The aim of the present study was to investigate the relationship between nematode
      infection and the ontogeny and diet of the lizard Tropidurus torquatus from a
      rocky outcrop in the state of Minas Gerais, south-eastern Brazil. Eighty-nine of
      110 lizards examined (81.9%) harboured nematodes. Two nematode species were
      identified, namely, Physaloptera lutzi in the stomach and Parapharyngodon bainae
      in the intestine, with prevalence values of 67.3 and 60.0%, respectively. The
      lizard diet was composed mainly of ants, other hymenopterans, beetles and flowers
      of the species Centrosema coriaceum (Fabaceae). Host body size was positively
      correlated with nematode abundance, with adults more heavily parasitized than
      juveniles. The consumption of C. coriaceum had a negative effect on the abundance
      of both nematode species, suggesting that this plant may possess anthelmintic
      properties. The probability of a higher worm burden in adult hosts is likely
      linked with a longer exposure time to infective stages. Beetles, ants and
      hymenopterans appear to be the main intermediate hosts for P. lutzi. In general,
      ontogeny and diet composition determine the structure of the helminth community
      in this species of lizard. 

PMID- 22989707
TI  - Oxytocin discontinuation during active labor in women who undergo labor
      induction.
AB  - OBJECTIVE: The purpose of this study was to determine whether there is an
      increase in the cesarean delivery rate in women who undergo induction when
      oxytocin is discontinued in the active phase of labor. STUDY DESIGN: We conducted
      a prospective randomized controlled trial of women who underwent induction of
      labor at term; they were assigned randomly to either routine oxytocin use
      (routine) or oxytocin discontinuation (DC) once in active labor. Analysis was by
      intention to treat. RESULTS: Two hundred fifty-two patients were eligible for
      study analysis: 127 patients were assigned randomly to the routine group and 125
      patients were assigned randomly to the DC group. Cesarean delivery rate was
      similar between the groups (routine, 25.2% [n = 32] vs the DC group, 19.2% [n =
      24]; P = .25). There was a higher chorioamnionitis rate and slightly longer
      active phase in those women who were assigned to the DC group. In adjusted
      analysis, the rate of chorioamnionitis was not different by randomization group
      but was explained by the duration of membrane rupture and intrauterine pressure
      catheter placement. CONCLUSION: Discontinuation of oxytocin in active labor after
      labor induction does not increase the cesarean delivery rate significantly.

PMID- 22989708
TI  - Predictors of atopic dermatitis phenotypes and severity: roles of serum
      immunoglobulins and filaggrin gene mutation R501X.
AB  - BACKGROUND: Atopic dermatitis (AD), the most common chronic relapsing skin
      condition of infancy and childhood, is a complex multifactorial disease, which
      arises from the interaction between strong genetic and environmental factors.
      OBJECTIVE: To investigate the roles of several factors on the severity of AD
      including FLG R501X gene mutation, serum immunoglobulin (Ig) levels, atopy and
      accompanying allergic disorders. METHOD: Children were genotyped for the mutation
      in FLG R501X gene. Serum levels of major Ig isotypes, atopy and accompanying
      allergic disorders were assessed. RESULTS: Study group consisted of 49 patients
      (M: 26, F: 23) with a mean age of 4.9+/-3.6 years and control group consisted of
      50 children (M: 30, F: 20) with a mean age of 3.8+/-2.8 years. Genotyping of
      R501X mutation revealed risk alleles in none of the children in study group or
      control group. IgG z-scores were significantly higher in patients with AD
      compared to controls (-0.97+/-1.13 vs 1.48+/-1.02, p=0.026). There was a positive
      trend in IgG z-scores and a negative trend in IgA z-scores across the severity of
      AD. History of recurrent infections was significantly associated with asthma
      and/or AR (47.8% in patients with asthma/AR vs 3.8% in those without). Children
      with low IgG or IgA levels presented at an earlier age with lower rates of atopy
      and mild type AD. CONCLUSION: In a sample of Turkish children, FLG R501X
      genotyping revealed no risk alleles in variable severities of AD or healthy
      controls. Our data suggest that IgG and IgA levels might have a role in
      phenotypic features of AD in terms of severity and atopic sensitisation.

PMID- 22989709
TI  - Target mRNA inhibition by oligonucleotide drugs in man.
AB  - Oligonucleotide delivery in vivo is commonly seen as the principal hurdle to the
      successful development of oligonucleotide drugs. In an analysis of 26
      oligonucleotide drugs recently evaluated in late-stage clinical trials we found
      that to date at least half have demonstrated suppression of the target mRNA
      and/or protein levels in the relevant cell types in man, including those present
      in liver, muscle, bone marrow, lung, blood and solid tumors. Overall, this
      strongly implies that the drugs are being delivered to the appropriate disease
      tissues. Strikingly we also found that the majority of the drug targets of the
      oligonucleotides lie outside of the drugable genome and represent new mechanisms
      of action not previously investigated in a clinical setting. Despite the high
      risk of failure of novel mechanisms of action in the clinic, a subset of the
      targets has been validated by the drugs. While not wishing to downplay the
      technical challenges of oligonucleotide delivery in vivo, here we demonstrate
      that target selection and validation are of equal importance for the success of
      this field.

PMID- 22989710
TI  - Binding of two DNA molecules by type II topoisomerases for decatenation.
AB  - Topoisomerases (topos) maintain DNA topology and influence DNA transaction
      processes by catalysing relaxation, supercoiling and decatenation reactions. In
      the cellular milieu, division of labour between different topos ensures
      topological homeostasis and control of central processes. In Escherichia coli,
      DNA gyrase is the principal enzyme that carries out negative supercoiling, while
      topo IV catalyses decatenation, relaxation and unknotting. DNA gyrase apparently
      has the daunting task of undertaking both the enzyme functions in mycobacteria,
      where topo IV is absent. We have shown previously that mycobacterial DNA gyrase
      is an efficient decatenase. Here, we demonstrate that the strong decatenation
      property of the enzyme is due to its ability to capture two DNA segments in
      trans. Topo IV, a strong dedicated decatenase of E. coli, also captures two
      distinct DNA molecules in a similar manner. In contrast, E. coli DNA gyrase,
      which is a poor decatenase, does not appear to be able to hold two different DNA
      molecules in a stable complex. The binding of a second DNA molecule to GyrB/ParE
      is inhibited by ATP and the non-hydrolysable analogue, AMPPNP, and by the
      substitution of a prominent positively charged residue in the GyrB N-terminal
      cavity, suggesting that this binding represents a potential T-segment positioned
      in the cavity. Thus, after the GyrA/ParC mediated initial DNA capture, GyrB/ParE
      would bind efficiently to a second DNA in trans to form a T-segment prior to
      nucleotide binding and closure of the gate during decatenation.

PMID- 22989711
TI  - Chromatin signature discovery via histone modification profile alignments.
AB  - We report on the development of an unsupervised algorithm for the genome-wide
      discovery and analysis of chromatin signatures. Our Chromatin-profile Alignment
      followed by Tree-clustering algorithm (ChAT) employs dynamic programming of
      combinatorial histone modification profiles to identify locally similar chromatin
      sub-regions and provides complementary utility with respect to existing methods.
      We applied ChAT to genomic maps of 39 histone modifications in human CD4(+) T
      cells to identify both known and novel chromatin signatures. ChAT was able to
      detect chromatin signatures previously associated with transcription start sites
      and enhancers as well as novel signatures associated with a variety of regulatory
      elements. Promoter-associated signatures discovered with ChAT indicate that
      complex chromatin signatures, made up of numerous co-located histone
      modifications, facilitate cell-type specific gene expression. The discovery of
      novel L1 retrotransposon-associated bivalent chromatin signatures suggests that
      these elements influence the mono-allelic expression of human genes by shaping
      the chromatin environment of imprinted genomic regions. Analysis of long gene
      associated chromatin signatures point to a role for the H4K20me1 and H3K79me3
      histone modifications in transcriptional pause release. The novel chromatin
      signatures and functional associations uncovered by ChAT underscore the ability
      of the algorithm to yield novel insight on chromatin-based regulatory mechanisms.

PMID- 22989712
TI  - The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of
      Telomeres.
AB  - Approximately 10% of all cancers, but a higher proportion of sarcomas, use the
      recombination-based alternative lengthening of telomeres (ALT) to maintain
      telomeres. Two RecQ helicase genes, BLM and WRN, play important roles in
      homologous recombination repair and they have been implicated in telomeric
      recombination activity, but their precise roles in ALT are unclear. Using
      analysis of sequence variation present in human telomeres, we found that a WRN-
      ALT+ cell line lacks the class of complex telomere mutations attributed to inter
      telomeric recombination in other ALT+ cell lines. This suggests that WRN
      facilitates inter-telomeric recombination when there are sequence differences
      between the donor and recipient molecules or that sister-telomere interactions
      are suppressed in the presence of WRN and this promotes inter-telomeric
      recombination. Depleting BLM in the WRN- ALT+ cell line increased the mutation
      frequency at telomeres and at the MS32 minisatellite, which is a marker of ALT.
      The absence of complex telomere mutations persisted in BLM-depleted clones, and
      there was a clear increase in sequence homogenization across the telomere and
      MS32 repeat arrays. These data indicate that BLM suppresses unequal sister
      chromatid interactions that result in excessive homogenization at MS32 and at
      telomeres in ALT+ cells.

PMID- 22989715
TI  - Matrix metalloproteinases -1, -2, -3, -7, -8, -12, and -13 in gingival crevicular
      fluid during orthodontic tooth movement: a longitudinal randomized split-mouth
      study.
AB  - This randomized split-mouth study aimed to examine the levels of matrix
      metalloproteinases (MMPs) -1, -2, -3, -7, -8, -12, and -13 in the gingival
      crevicular fluid (GCF) at different time points during orthodontic tooth
      movement. A total of 16 healthy orthodontic subjects (7 females, 9 males; mean
      age, 17.7 years) who needed their first upper premolars extracted were enrolled.
      One randomly chosen maxillary canine was subjected to a distalizing force and was
      considered to be the test side. The contralateral canine, which was not subjected
      to any force but was included in the orthodontic appliance, was used as a control
      side. GCF sampling was performed at both the mesial (tension) and distal
      (pressure) test and control sites at baseline, immediately before applying the
      orthodontic appliance, and after 1 and 24 hours and 7, 14, and 21 days. A
      multiplexed bead immunoassay was used to analyse the GCF samples. The mean levels
      of the MMP-1, -2, -3, -7, -8, -12, and -13 were not significantly different
      between the test and control groups in each time showed. The comparisons between
      the tension and pressure sites were also not significantly different at each
      individual time. A few variations focused on MMP-1 and -3, but the expression of
      MMP-8 was higher than that of the other MMPs. MMPs are released in sufficient
      quantities such that tooth movement occurs but with no significant increase in
      GCF levels. 

PMID- 22989714
TI  - Global transcriptional control by glucose and carbon regulator CcpA in
      Clostridium difficile.
AB  - The catabolite control protein CcpA is a pleiotropic regulator that mediates the
      global transcriptional response to rapidly catabolizable carbohydrates, like
      glucose in Gram-positive bacteria. By whole transcriptome analyses, we
      characterized glucose-dependent and CcpA-dependent gene regulation in Clostridium
      difficile. About 18% of all C. difficile genes are regulated by glucose, for
      which 50% depend on CcpA for regulation. The CcpA regulon comprises genes
      involved in sugar uptake, fermentation and amino acids metabolism, confirming the
      role of CcpA as a link between carbon and nitrogen pathways. Using combination of
      chromatin immunoprecipitation and genome sequence analysis, we detected 55 CcpA
      binding sites corresponding to ~140 genes directly controlled by CcpA. We defined
      the C. difficile CcpA consensus binding site (cre(CD) motif), that is,
      'RRGAAAANGTTTTCWW'. Binding of purified CcpA protein to 19 target cre(CD) sites
      was demonstrated by electrophoretic mobility shift assay. CcpA also directly
      represses key factors in early steps of sporulation (Spo0A and SigF).
      Furthermore, the C. difficile toxin genes (tcdA and tcdB) and their regulators
      (tcdR and tcdC) are direct CcpA targets. Finally, CcpA controls a complex and
      extended regulatory network through the modulation of a large set of regulators.

PMID- 22989713
TI  - The DUBm subunit Sgf11 is required for mRNA export and interacts with Cbp80 in
      Drosophila.
AB  - SAGA/TFTC is a histone acetyltransferase complex that has a second enzymatic
      activity because of the presence of a deubiquitination module (DUBm). Drosophila
      DUBm consists of Sgf11, ENY2 and Nonstop proteins. We show that Sgf11 has other
      DUBm-independent functions. It associates with Cbp80 component of the cap-binding
      complex and is thereby recruited onto growing messenger ribonucleic acid (mRNA);
      it also interacts with the AMEX mRNA export complex and is essential for hsp70
      mRNA export, as well as for general mRNA export from the nucleus. Thus, Sgf11
      functions as a component of both SAGA DUBm and the mRNA biogenesis machinery.

PMID- 22989716
TI  - Intra-abdominal fluid extravasation during hip arthroscopy: a survey of the
      MAHORN group.
AB  - PURPOSE: The purpose of this study was to survey experts in the field of hip
      arthroscopy from the Multicenter Arthroscopy of the Hip Outcomes Research Network
      (MAHORN) group to determine the frequency of symptomatic intra-abdominal fluid
      extravasation (IAFE) after arthroscopic hip procedures, identify potential risk
      factors, and develop preventative measures and treatment strategies in the event
      of symptomatic IAFE. METHODS: A survey was sent to all members of the MAHORN
      group. Surveys collected data on general hip arthroscopy settings, including pump
      pressure and frequency of different hip arthroscopies performed, as well as
      details on cases of symptomatic IAFE. Responses to the survey were documented and
      analyzed. RESULTS: Fifteen hip arthroscopists from the MAHORN group were
      surveyed. A total of 25,648 hip arthroscopies between 1984 and 2010 were
      reviewed. Arthroscopic procedures included capsulotomies, labral reattachment
      after acetabuloplasty, peripheral compartment arthroscopy, and osteoplasty of the
      femoral head-neck junction. Of the arthroscopists, 7 (47%) had 1 or more cases of
      IAFE (40 cases reported). The prevalence of IAFE in this study was 0.16% (40 of
      25,650). Significant risk factors associated with IAFE were higher arthroscopic
      fluid pump pressure (P = .004) and concomitant iliopsoas tenotomy (P < .001). In
      all 40 cases, the condition was successfully treated without long-term sequelae.
      Treatment options included observation, intravenous furosemide, and Foley
      catheter placement, as well as 1 case of laparotomy. CONCLUSIONS: Symptomatic
      IAFE after hip arthroscopy is a rare occurrence, with an approximate prevalence
      of 0.16%. Prevention of IAFE should include close intraoperative and
      postoperative monitoring of abdominal distention, core body temperature, and
      hemodynamic stability. Concomitant iliopsoas tenotomy and high pump pressures may
      be risk factors leading to symptomatic IAFE. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 22989718
TI  - Effect of low-intensity pulsed ultrasound on the cartilage repair in people with
      mild to moderate knee osteoarthritis: a novel molecular mechanism.

PMID- 22989720
TI  - Relations or agreement between 6 minute walking distance and 10 meter walking
      speed?

PMID- 22989721
TI  - Airway contractility and remodeling: links to asthma symptoms.
AB  - Respiratory symptoms are largely caused by obstruction of the airways. In asthma,
      airway narrowing mediated by airway smooth muscle (ASM) contraction contributes
      significantly to obstruction. The spasmogens produced following exposure to
      environmental triggers, such as viruses or allergens, are initially responsible
      for ASM activation. However, the extent of narrowing of the airway lumen due to
      ASM shortening can be influenced by many factors and it remains a real challenge
      to decipher the exact role of ASM in causing asthmatic symptoms. Innovative
      tools, such as the forced oscillation technique, continue to develop and have
      been proven useful to assess some features of ASM function in vivo. Despite these
      technologic advances, it is still not clear whether excessive narrowing in asthma
      is driven by ASM abnormalities, by other alterations in non-muscle factors or
      simply because of the overexpression of spasmogens. This is because a multitude
      of forces are acting on the airway wall, and because not only are these forces
      constantly changing but they are also intricately interconnected. To counteract
      these limitations, investigators have utilized in vitro and ex vivo systems to
      assess and compare asthmatic and non-asthmatic ASM contractility. This review
      describes: 1- some muscle and non-muscle factors that are altered in asthma that
      may lead to airway narrowing and asthma symptoms; 2- some technologies such as
      the forced oscillation technique that have the potential to unveil the role of
      ASM in airway narrowing in vivo; and 3- some data from ex vivo and in vitro
      methods that probe the possibility that airway hyperresponsiveness is due to the
      altered environment surrounding the ASM or, alternatively, to a hypercontractile
      ASM phenotype that can be either innate or acquired.

PMID- 22989722
TI  - Is the circulating plasma volume sufficiently maintained? Fluid management of an
      aneurysmal subarachnoid hemorrhage in the acute phase.
AB  - Cerebral vasospasm is a well-known cause of mortality and morbidity following
      aneurysmal subarachnoid hemorrhage (SAH). Prevention of symptomatic cerebral
      vasospasm is the basic management after SAH. Numerous pharmaceutical therapies
      and endovascular treatments are available against  cerebral vasospasm, but none
      of them have so far proven to improve the outcome. We have focused on maintaining
      the circulation volume in order to prevent cerebral vasospasm. But to maintain
      the central venous pressure, huge infusion volume was required, and hyponatremia
      was frequently observed  due to natriuresis and osmotic diuresis. Excessive
      natriuresis and diuresis cannot be managed through sodium and water replacement,
      since sodium replacement induces further natriuresis and diuresis (desalination),
      and water replacement induces hyponatremia. We therefore administered
      fludrocortisone  and hydrocortisone to inhibit excessive natriuresis and
      diuresis. The efficacy of sodium reabsorption therapy is extremely high to
      maintain the circulation volume that might have a therapeutic effect to prevent
      cerebral vasospasm. In this article, we review our institution's experience 
      regarding the management of patients with aneurysmal SAH and also discuss the
      importance of water and sodium balance when managing such patients.

PMID- 22989724
TI  - The role of tryptophan side chains in membrane protein anchoring and hydrophobic
      mismatch.
AB  - Tryptophan (Trp) is abundant in membrane proteins, preferentially residing near
      the lipid-water interface where it is thought to play a significant anchoring
      role. Using a total of 3 MUs of molecular dynamics simulations for a library of
      hydrophobic WALP-like peptides, a long poly-Leu alpha-helix, and the methyl
      indole analog, we explore the thermodynamics of the Trp movement in membranes
      that governs the stability and orientation of transmembrane protein segments. We
      examine the dominant hydrogen-bonding interactions between the Trp and lipid
      carbonyl and phosphate moieties, cation-pi interactions to lipid choline
      moieties, and elucidate the contributions to the thermodynamics that serve to
      localize the Trp, by ~4 kcal/mol, near the membrane glycerol backbone region. We
      show a striking similarity between the free energy to move an isolated Trp side
      chain to that found from a wide range of WALP peptides, suggesting that the
      location of this side chain is nearly independent of the host transmembrane
      segment. Our calculations provide quantitative measures that explain Trp's role
      as a modulator of responses to hydrophobic mismatch, providing a deeper
      understanding of how lipid composition may control a range of membrane active
      peptides and proteins.

PMID- 22989723
TI  - Oral squamous carcinoma cells secrete RANKL directly supporting osteolytic bone
      loss.
AB  - OBJECTIVE: Local invasion of bone is a frequent complication of oral squamous
      cell carcinoma (OSCC). Development of these osteolytic lesions is mediated by
      osteoclasts. Receptor activation of NF-kappaB ligand (RANKL) signaling,
      counteracted by osteoprotegerin (OPG), regulates osteoclastogenesis. Previous
      studies in rodent models have demonstrated that inhibition of RANKL decreases
      tumor growth and lesions within bone. However, the contributory role of OSCC
      cells to this disease process has yet to be defined. METHODS: RANKL expression
      was assessed in a panel of OSCC cell lines by qPCR, flow cytometry, and ELISA.
      Induction of osteoclastogenesis was assessed by co-culture with macrophages or
      with OSCC-derived conditioned medium. In an animal model of bone invasion, nude
      mice were injected intratibially with UMSCC-11B cells expressing a RANKL
      luciferase promoter to detect tumor-derived RANKL activity. Osteolytic lesions
      were analyzed by X-ray, micro-CT, and histological methods. RANKL expression was
      assessed in human OSCC tissues by immunohistochemistry. RESULTS: We demonstrated
      that OSCCs express varied levels of all RANKL isoforms, both membrane-bound and
      soluble RANKL. Both co-culture and treatment with OSCC-conditioned media induced
      osteoclastogenesis. In mice, we demonstrated human RANKL promoter activity during
      bone invasion. Over the course of the experiment, animals suffered osteolytic
      lesions as RANKL-driven luciferase expression increased with time. After 8weeks,
      human-derived RANKL was detected in areas of bone resorption by
      immunohistochemistry. Similar epithelial RANKL expression was detected in human
      OSCC tissues. CONCLUSION: These data demonstrate the ability of OSCCs to produce
      RANKL, directly altering the tumor microenvironment to increase
      osteoclastogenesis and mediate local bone invasion.

PMID- 22989725
TI  - Membrane fluidity and activity of membrane ATPases in human erythrocytes under
      the influence of polyhydroxylated fullerene.
AB  - The influence of fullerenol on the activities of human erythrocyte membrane
      ATPases and the fluidity of the plasma membrane as well as the possibility of
      fullerenol incorporation into the plasma membrane were investigated. Fullerenol
      at concentrations up to 150 MUg/mL induced statistically significant decreases in
      the anisotropy of 1-anilino-8-naphthalene sulfonate (ANS) (14%), N,N,N-trimethyl
      4-(6-phenyl-1,3,5,-hexatrien-1-yl)phenylammonium p-toluenesulfonate (TMA-DPH)
      (7.5%) and 1,6-diphenyl-1,3,5-hexatriene (DPH) (9.5%) after a 1-hour incubation
      at 37 degrees C. The effect disappeared for ANS and TMA-DPH, but not for DPH,
      after washing out the fullerenol. Incubation of erythrocyte membranes with
      fullerenol led to decreases in the activities of Na(+),K(+)-ATPase (to 23% of the
      control value), Ca(2+)-ATPase (to 16% of control) and Mg(2+)-ATPase (to 22% of
      control). Washing out the fullerenol lessened the inhibition of the Na(+),K(+)
      ATPase (37% of control) and Ca(2+)-ATPase (23.5% of control); however, it did not
      influence Mg(2+)-ATPase activity. Furthermore, fullerenol could associate with
      erythrocyte plasma membranes. Our results suggest that fullerenol associates
      primarily with the surface of the plasma membrane; however, it can also migrate
      deeper inside the membrane. Moreover, fullerenol influences membrane ATPases so
      that it may modulate ion transport across membranes.

PMID- 22989726
TI  - A (2)H solid-state NMR study of the effect of antimicrobial agents on intact
      Escherichia coli without mutating.
AB  - Solid-state nuclear magnetic resonance (NMR) is a useful tool to probe the
      organization and dynamics of phospholipids in bilayers. The interactions of
      molecules with membranes are usually studied with model systems; however, the
      complex composition of biological membranes motivates such investigations on
      intact cells. We have thus developed a protocol to deuterate membrane
      phospholipids in Escherichia coli without mutating to facilitate (2)H solid-state
      NMR studies on intact bacteria. By exploiting the natural lipid biosynthesis
      pathway and using perdeuterated palmitic acid, our results show that 76%
      deuteration of the phospholipid fatty acid chains was attained. To verify the
      responsiveness of these membrane-deuterated E. coli, the effect of known
      antimicrobial agents was studied. (2)H solid-state NMR spectra combined to
      spectral moment analysis support the insertion of the antibiotic polymyxin B
      lipid tail in the bacterial membrane. The use of membrane-deuterated bacteria was
      shown to be important in cases where antibiotic action of molecules relies on the
      interaction with lipopolysaccharides. This is the case of fullerenol
      nanoparticles which showed a different effect on intact cells when compared to
      dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol membranes. Our
      results also suggest that membrane rigidification could play a role in the
      biocide activity of the detergent cetyltrimethyammonium chloride. Finally, the
      deuterated E. coli were used to verify the potential antibacterial effect of a
      marennine-like pigment produced by marine microalgae. We were able to detect a
      different perturbation of the bacteria membranes by intra- and extracellular
      forms of the pigment, thus providing valuable information on their action
      mechanism and suggesting structural differences.

PMID- 22989727
TI  - Role of membrane oxidation in controlling the activity of human group IIa
      secretory phospholipase A(2) toward apoptotic lymphoma cells.
AB  - The membranes of healthy lymphocytes normally resist hydrolysis by secretory
      phospholipase A(2). However, they become susceptible during the process of
      apoptosis. Previous experiments have demonstrated the importance of certain
      physical changes to the membrane during cell death such as a reduction in
      membrane lipid order and exposure of phosphatidylserine on the membrane surface.
      Nevertheless, those investigations also showed that at least one additional
      factor was required for rapid hydrolysis by the human group IIa phospholipase
      isozyme. This study was designed to test the possibility that oxidation of
      membrane lipids is the additional factor. Flow cytometry and confocal microscopy
      with a fluorescent probe of oxidative potential suggested that oxidation of the
      plasma membrane occurs during apoptosis stimulated by thapsigargin. When
      oxidative potential was high, the activity of human group IIa secretory
      phospholipase A(2) was enhanced 30- to 100-fold compared to that observed with
      conditions sufficient for maximal hydrolysis by other secretory phospholipase
      A(2) isoforms. Direct oxidation of cell membranes with either of two oxidizing
      agents also stimulated hydrolysis by secretory phospholipase A(2). Both oxidizers
      caused externalization of phosphatidylserine, but a change in lipid order did not
      always occur. These results demonstrated that membrane oxidation strongly
      stimulates human group IIa secretory phospholipase A(2) activity toward apoptotic
      cells. Interestingly, the change in membrane order, previously thought to be
      imperative for high rates of hydrolysis, was not required when membrane lipids
      were oxidized. Whether phosphatidylserine exposure is still necessary with
      oxidation remains unresolved since the two events could not be deconvoluted.

PMID- 22989729
TI  - Glycosaminoglycan profiles in the uterus of adult ovariectomized rats treated
      with estrogen and progestagen.
AB  - OBJECTIVES: To evaluate the effects of conjugated equine estrogens (CE) alone or
      in combination with medroxyprogesterone acetate (MPA) on glycosaminoglycans
      (GAGs) in the cervix and horns of the rat uterus. STUDY DESIGN: Thirty days after
      ovariectomy, adult rats were randomly divided into four groups: GI, control
      (treated with drug vehicle); GII, CE (50 MUg/kg per day); GIII, MPA (0.2mg/kg per
      day), and GIV, CE+MPA (doses as in GII and GIII). Drugs and vehicle were given by
      gavage during 28 days. Afterwards the animals were anesthetized, the cervix and
      uterine horns were dissected out and the middle portion fixed in 10% formaldehyde
      solution; other portions were fixed in acetone for histological examination and
      glycosaminoglycan quantification, respectively. Agarose gel electrophoresis was
      used for sulfated GAG analyses, and hyaluronic acid was assayed with an ELISA
      like method. Statistical analysis was done by the Student's t test and the Tukey
      Kramer test (P<0.05). RESULTS: The cervix and uterine horn structures presented
      signs of atrophy in the control group (GI). The other groups, mainly groups III
      and IV, had histological aspects of proliferation. In all groups the
      concentration of sulfated GAGs (especially dermatan sulfate) was higher than that
      of non-sulfated GAGs, both in cervix and in uterine horns. Estrogens increased
      sulfated GAG concentration at the cervix and the horn, whereas in uterine horns
      the amounts of sulfated GAGs were decreased after estrogens plus MPA treatment.
      The concentration of hyaluronic acid in uterine horns was higher than in
      cervices. CONCLUSIONS: The profiling and amounts of glycosaminoglycans in the two
      portions of the rat uterus are uneven. Dermatan sulfate occurs in higher
      concentrations in both cervix and uterine horns. Sulfated GAGs in rat cervix were
      increased by estrogens plus MPA, but were decreased by MPA alone in uterine
      horns.

PMID- 22989728
TI  - Protective effects of NHE1 inhibition with sabiporide in an experimental model of
      asphyxia-induced cardiac arrest in piglets.
AB  - The present study investigated the protective effects of a novel NHE1 selective
      inhibitor, sabiporide, in a porcine model of asphyxia-induced cardiac arrest.
      Asphyxial cardiac arrest was induced by endotracheal tube clamping (ETC). The
      animals remained untreated for 3 min after loss of aortic pulsations (LOAP), and
      followed by chest compression and defibrillation. Sixteen of eighteen pigs had
      return of spontaneous circulation (ROSC), and were randomly assigned to two study
      groups. Group 1: vehicle control. Group 2: 3mg/kg sabiporide was given at 15 min
      after ROSC. Post-arrest myocardial dysfunction was present in both groups, and
      progressed over hours. Animals treated with sabiporide had less wall motion
      abnormality and higher left ventricular ejection fraction than control animals
      (33% in control group vs. 47% in sabiporide group). Sabopiride treatment also
      significantly improved post-arrest arterial blood pressure by 25% and cardiac
      stroke volume by 44%, and improved mixed-venous blood oxygen saturation by 38%
      and oxygen delivery by 118%. Furthermore, compared to the control group, the
      sabiporide group also had higher blood flows in the brain, heart, kidney, liver
      and spleen at 30 min after ROSC. There was no significant blood flow difference
      in distal ileum mucosa between control and sabiporide groups. In addition,
      sabiporide treatment significantly reduced cardiac myeloperoxidase (MPO) activity
      by 53% and cardiac troponin I by 51%, and reduced the plasma level of TNF-alpha
      by 52% and IL-6 by 41%. This study shows that post-arrest pharmacological
      conditioning with sabiporide affords protection from whole body ischemia
      reperfusion injury in this model of asphyxia-induced cardiac arrest and
      resuscitation.

PMID- 22989730
TI  - Persistent neck disease after chemoradiation for head and neck squamous cell
      carcinoma.
AB  - OBJECTIVE: This study aimed to identify the incidence of residual viable neck
      disease in patients with mucosal squamous cell carcinoma of the upper aero
      digestive tract, following primary chemoradiation at a tertiary centre. STUDY
      DESIGN: Retrospective review. METHODS: Retrospective chart review of patients
      treated with primary chemoradiation for squamous cell carcinoma of the aero
      digestive tract between August 2001 and August 2008. Neck status pre- and post
      treatment was the primary focus. RESULTS: Forty-two patients with node-positive
      disease prior to chemoradiation were included. Thirty-seven (88.1 per cent)
      achieved complete response to treatment: no patient in this group underwent neck
      dissection, five died due to recurrence at the primary site or distant
      metastasis, and none suffered neck recurrence. Five (11.9 per cent) patients
      achieved partial response to chemoradiation and underwent neck dissection; viable
      tumour was found in one patient. CONCLUSION: Our data support conservative
      management of the neck in patients with complete response to chemoradiation, and
      consolidation neck dissection in patients with partial response.

PMID- 22989731
TI  - Identifying children at risk for being bullies in the United States.
AB  - OBJECTIVE: To identify risk factors associated with the greatest and lowest
      prevalence of bullying perpetration among U.S. children. METHODS: Using the 2001
      2002 Health Behavior in School-Aged Children, a nationally representative survey
      of U.S. children in 6th-10th grades, bivariate analyses were conducted to
      identify factors associated with any (once or twice or more), moderate (two to
      three times/month or more), and frequent (weekly or more) bullying. Stepwise
      multivariable analyses identified risk factors associated with bullying.
      Recursive partitioning analysis (RPA) identified risk factors which, in
      combination, identify students with the highest and lowest bullying prevalence.
      RESULTS: The prevalence of any bullying in the 13,710 students was 37.3%,
      moderate bullying was 12.6%, and frequent bullying was 6.6%. Characteristics
      associated with bullying were similar in the multivariable analyses and RPA
      clusters. In RPA, the highest prevalence of any bullying (67%) accrued in
      children with a combination of fighting and weapon-carrying. Students who carry
      weapons, smoke, and drink alcohol more than 5 to 6 days/week were at greatest
      risk for moderate bullying (61%). Those who carry weapons, smoke, have more than
      one alcoholic drink per day, have above-average academic performance,
      moderate/high family affluence, and feel irritable or bad-tempered daily were at
      greatest risk for frequent bullying (68%). CONCLUSIONS: Risk clusters for any,
      moderate, and frequent bullying differ. Children who fight and carry weapons are
      at greatest risk of any bullying. Weapon-carrying, smoking, and alcohol use are
      included in the greatest risk clusters for moderate and frequent bullying. Risk
      group categories may be useful to providers in identifying children at the
      greatest risk for bullying and in targeting interventions.

PMID- 22989732
TI  - Potential savings from redetermining disability among children receiving
      supplemental security income benefits.
AB  - OBJECTIVE: To compare the costs of redetermining disability to potential savings
      in Supplemental Security Income payments associated with different strategies for
      implementing Continuing Disability Reviews (CDRs) among children potentially
      enrolled in SSI from 2012 to 2021. METHODS: We reviewed publicly available
      reports from the Social Security Administration and Government Accountability
      Office to estimate costs and savings. We considered CDRs for children ages 1-17
      years, excluding mandated low-birth weight and age 18 redeterminations that SSA
      routinely has performed. RESULTS: If in 2012 the Social Security Administration
      performs the same number of CDRs for children as in 2010 (16,677, 1% of
      eligibles) at a cessation rate of 15%, the agency would experience net savings of
      approximately $145 million in benefit payments. If CDR numbers increased to the
      greatest level ever (183,211, 22% of eligibles, in 1999) at the same cessation
      rate, the agency would save approximately $1.6 billion in benefit payments.
      DISCUSSION: Increasing the numbers of CDRs for children represents a considerable
      opportunity for savings. Recognizing the dynamic nature of disability, the agency
      could reassess the persistence of disability systematically; doing so could free
      up resources from children who are no longer eligible and help the agency better
      direct its benefits to recipients with ongoing disability and whose families need
      support to meet the extra costs associated with raising a child with a major
      disability.

PMID- 22989733
TI  - Analysis of failed Van Straten LPM proximal interphalangeal prostheses.
AB  - The two-piece Van Straten Leuwen Poeschmann Metal (LPM) prosthesis was intended
      for the proximal interphalangeal joints. However, revision rates of 29% after 19
      months were reported, as well as massive osteolysis. Five failed LPM titanium
      niobium coated cobalt chromium components were obtained, three distal and two
      proximal, and subjected to a forensic retrieval analysis. Components were
      analyzed using a Talysurf contacting profilometer, ZYGO noncontacting
      profilometer, and environmental-scanning electron microscope. All components were
      heavily worn. In some regions the titanium-niobium coating had been scratched and
      penetrated. Elsewhere this coating had been removed where there was minimal
      scratching, which may have been due to corrosion between the coating and
      substrate. The osteolysis reported clinically was likely to be linked to the wear
      debris from the failed titanium-niobium coating and substrate.

PMID- 22989734
TI  - Flexor tendon retrieval - a modified technique.

PMID- 22989735
TI  - Results of surgical techniques for re-innervation of the triceps as additional
      procedures for patients with upper root injuries.
AB  - Patients with injuries restricted to the upper and middle trunks of the brachial
      plexus may obtain recovery of elbow extension via the lower trunk, which makes it
      difficult to assess the real effect of interventions to restore the triceps
      function in such cases. This study aimed to determine the impact of surgical
      strategies for re-innervation of the triceps in individuals with partial injuries
      of the brachial plexus. Patients were divided into two groups. Group 1 consisted
      of 21 participants in whom the surgery included one technique for re-innervation
      of elbow extension. In this group, six different extra- or intra-plexal donors
      were targeted to one of the motor branches of the triceps muscle. Group 2 was
      composed of 24 controls in which the reconstruction did not include any
      intervention for recovering triceps function. The individuals who underwent
      intervention for re-innervation of the triceps obtained significantly better
      outcomes for elbow extension than the controls.

PMID- 22989736
TI  - Dislocation of the hamate and its possible mechanism.

PMID- 22989737
TI  - Sports medicine, confidentiality and the press.
AB  - OBJECTIVE: To analyse athletes' medical information disclosed by English
      newspapers. METHODS: Ten daily national newspapers, nine Sunday newspapers and
      one local newspaper were studied during March 2010 for media releases relating to
      the medical conditions of athletes. RESULTS: Three hundred and thirty-three
      newspapers were reviewed revealing 5640 specific bulletins regarding athletes'
      health. Daily national newspapers averaged 18.72 daily bulletins, Sunday
      newspapers 11.86 and one local newspaper reviewed 6.07. The frequency with which
      various sports had their athletes' medical details published was analysed.
      Football accounted for 83.78%. The information source in 77.32% of articles is
      not clearly stated. The patient was only responsible in 6.10% of cases, where the
      source of attribution is clear. CONCLUSIONS: English newspapers are replete with
      athletes' medical details, with football dominant. A significant risk to
      clinicians' professional status exists if they collude to release the un
      consented confidential medical information to those with no direct involvement in
      athletes' medical care. Athletes' education as to their rights as patients and to
      sports medicine professionals as to their obligations are urgently required.

PMID- 22989738
TI  - Intra-annual nutrient flux in Pinus taeda.
AB  - Intra-annual nutrient (nitrogen, phosphorus, potassium, calcium and magnesium)
      flux was quantified for Pinus taeda L. at a nutrient-poor, well-drained sandy
      site in Scotland County, NC, USA where a 2 * 2 factorial of irrigation and
      nutrition was applied in four replications in a 10-year-old stand with 1200 stems
      ha(-1). Treatments were applied with the goal of providing optimum nutrition (no
      nutritional deficiencies) and water availability. Component (foliage, branch,
      stem and root) nutrient content was estimated monthly for 2 years using nutrient
      concentration and phenology assessments combined with destructive harvests.
      Positive flux values indicated nutrient accumulation in the trees while negative
      values indicated nutrient loss from the trees. Fertilization significantly
      increased nitrogen, phosphorus, potassium, calcium and magnesium flux 140%, on
      average, over non-fertilized. Irrigation significantly increased calcium flux 28%
      while there was no significant irrigation effect on nitrogen, phosphorus,
      potassium or magnesium. Maximum nutrient fluxes (kg ha(-1) day(-1)) for non
      fertilized and fertilized stands were 0.36 and 1.05 for nitrogen, 0.042 and 0.095
      for phosphorus, 0.13 and 0.51 for potassium, 0.27 and 0.42 for calcium, and 0.04
      and 0.12 for magnesium, respectively. Maximum flux was coincident with ephemeral
      tissue (foliage and fine root) development and likely would be higher in stands
      with more foliage than those observed in this study (projected leaf area indices
      were 1.5 and 3.0 for the non-fertilized and fertilized stands). Minimum nutrient
      fluxes (kg ha(-1) day(-1)) for non-fertilized and fertilized stands were -0.18
      and -0.42 for nitrogen, -0.029 and -0.070 for phosphorus, -0.05 and -0.18 for
      potassium, -0.04 and -0.05 for calcium, and -0.02 and -0.03 for magnesium,
      respectively. Minimum fluxes were typically observed in the dormant season and
      were linked to foliage senescence and branch death. Foliage and branch component
      nutrient contents were out of phase for nitrogen, phosphorus, potassium and
      magnesium, indicating nutrient retranslocation and storage in branches prior to
      foliage development and after foliage senescence. In contrast to current
      operational fertilizer programs which often target winter application these data
      suggest the best application times would be during foliage development.

PMID- 22989739
TI  - Applying the dual-isotope conceptual model to interpret physiological trends
      under uncontrolled conditions.
AB  - The inter-relationships among delta(13)C and delta(18)O in tree ring cellulose
      and ring width have the potential to illuminate long-term physiological and
      environmental information in forest stands that have not been monitored. We
      examine how within-stand competition and environmental gradients affect ring
      widths and the stable isotopes of cellulose. We utilize a natural climate
      gradient across a catchment dominated by Douglas-fir and temporal changes in
      climate over an 8-year period. We apply a dual-isotope approach to infer
      physiological response of trees in differing crown dominance classes to temporal
      and spatial changes in environmental conditions using a qualitative conceptual
      model of the (13)C-(18)O relationship and by normalizing the data to minimize
      other variance. The delta(13)C and delta(18)O of cellulose were correlated with
      year-to-year variation in relative humidity and consistent with current isotope
      theory. Using a qualitative conceptual model of the (13)C-(18)O relationship and
      physiological knowledge about the species, we interpreted these changes as
      stomatal conductance responses to evaporative demand. Spatial variance between
      plots was not strong and seemed related to leaf nitrogen rather than any other
      environmental variable. Dominant trees responded to environmental gradients more
      consistently with current isotope theory as compared with other classes within
      the same stand. We found a correlation of stable isotopes with environmental
      variables is useful for assessing the impacts of environmental change over short
      time series and where growth varies only minimally with climate.

PMID- 22989740
TI  - Effects of exogenous auxin and ethylene on the Arabidopsis root proteome.
AB  - The phytohormones, auxin and ethylene, together control a wide range of
      physiological and developmental processes in plants. The lack of knowledge
      regarding how the underlying signaling processes are reflected at the protein
      level represents a major gap in understanding phytohormone signaling, including
      that mediated by crosstalk between auxin and ethylene. Herein is a parallel
      comparison of the effects of these two hormones on the Arabidopsis root proteome.
      Arabidopsis seedlings were exposed to 1 MUm indole-3-acetic acid (IAA, auxin) or
      1 MUm 1-amino-cyclopropane carboxylic acid (ACC) for 24h. Root protein extracts
      were fractionated using two-dimensional gel electrophoresis and the proteins that
      changed the most were analyzed by MALDI TOF/TOF mass spectrometry. Of the 500
      total spots that were matched across all gels, 24 were significantly different
      after IAA exposure, while seven others were different after ACC exposure. Using
      rigorous criteria, identities of eight proteins regulated by IAA and five
      regulated by ACC were assigned. Interestingly, although both hormones affected
      proteins associated with fundamental cellular processes, no overlap was observed
      among the proteins affected by auxin or ethylene treatment. This report provides
      a comparison of the effects of these two hormones relative to a control utilizing
      equivalent treatment regimes and suggests that, while these hormones communicate
      to control similar physiological and transcriptional processes, they have
      different effects on the most abundant proteins in Arabidopsis roots.

PMID- 22989741
TI  - Asking the question again: are cation exchange resins effective for the treatment
      of hyperkalemia?

PMID- 22989742
TI  - Anomalous insertion of the papillary muscle in a patient with sickle cell
      disease: a normal variant with no left ventricular outflow obstruction.

PMID- 22989743
TI  - Single leg balancing in ballet: effects of shoe conditions and poses.
AB  - The purpose of this study was to describe the effects of lower limb positioning
      and shoe conditions on stability levels of selected single leg ballet poses
      performed in demi-pointe position. Fourteen female non-professional ballet
      dancers (mean age of 18.4+/-2.8 years and mean body mass index of 21.5+/
      2.8kg/m(2)) who had practiced ballet for at least seven years, without any
      musculoskeletal impairment volunteered to participate in this study. A capacitive
      pressure platform allowed for the assessment of center of pressure variables
      related to the execution of three single leg ballet poses in demi pointe
      position: attitude devant, attitude derriere, and attitude a la second. Peak
      pressures, contact areas, COP oscillation areas, anterior-posterior and medio
      lateral COP oscillations and velocities were compared between two shoe conditions
      (barefoot versus slippers) and among the different poses. Barefoot performances
      produced more stable poses with significantly higher plantar contact areas,
      smaller COP oscillation areas and smaller anterior-posterior COP oscillations.
      COP oscillation areas, anterior-posterior COP oscillations and medio-lateral COP
      velocities indicated that attitude a la second is the least challenging and
      attitude derriere the most challenging pose.

PMID- 22989744
TI  - The dosing determines mutagenicity of hydrophobic compounds in the Ames II assay
      with metabolic transformation: passive dosing versus solvent spiking.
AB  - The Ames II bacterial mutagenicity assay is a new version of the standard Ames
      test for screening chemicals for genotoxic activity. However, the use of plastic
      micro-titer plates has drawbacks in the case of testing hydrophobic mutagens,
      since sorptive and other losses make it difficult to control and define the
      exposure concentrations, and they reduce availability for bacterial uptake or to
      the S9 enzymes. With passive dosing, a biocompatible polymer such as silicone is
      loaded with the test compound and acts as a partitioning source. It compensates
      for any losses and results in stable freely dissolved concentrations. Passive
      dosing using silicone O-rings was applied in the Ames II assay to measure PAH
      mutagenicity in strains TA98 and TAMix - a mixture of six different bacterial
      strains detecting six different base-pair substitutions - after metabolic
      activation by S9. Initially, 10 PAHs were tested with passive dosing from
      saturated O-rings, aiming at levels in the test medium close to aqueous
      solubility. Fluoranthene, pyrene and benzo(a)pyrene were mutagenic in both TA98
      and TAMix, whereas benz(a)anthracene was mutagenic in TA98 only. The
      concentration-dependent mutagenic activity of benzo(a)pyrene was then compared
      for passive dosing and solvent spiking. With spiking, nominal concentrations
      greatly exceeded aqueous solubility before mutagenicity was observed, due to
      sorptive losses and limiting dissolution kinetics. In contrast, the passive
      dosing concentration-response curves were more reproducible, and shifted towards
      lower concentrations by several orders of magnitude. This study raises
      fundamental questions about how to introduce hydrophobic test substances in the
      Ames II assay with biotransformation, since the measured mutagenicity not only
      depends on the compound potency but also on its supply, sorption and consumption
      during the assay.

PMID- 22989745
TI  - A novel microplate-based assay for screening radioprotectors and its validation
      based on DNA and membrane system.
AB  - Ionizing radiation leads to damage at various cellular and sub-cellular levels
      and can be prevented by radioprotectors. There are many in vitro and in vivo but
      rather expensive assays for screening of radioprotectors from natural and
      synthetic sources. We have developed a cell free radioprotector screening assay
      which involves bleaching of crocin pigment, isolated from saffron by radiolytic
      products of water. Any molecules/compounds which can inhibit the bleaching of the
      crocin will act as a radioprotector. The developed assay was further validated by
      the existing in vitro assays. Different radioprotectors have different level for
      inhibition of bleaching of crocin. The trends of radioprotection offered by
      crocin bleaching assay, plasmid relaxation and lipid peroxidation are
      TMG>FA>VA>Amifos>Trox, TMG>VA>FA>Amifos>Trox, and TMG>FA>Trox>VA>Amifos,
      respectively. We are getting different trends for different assays. This is
      because different drugs have different mechanisms of radioprotection in different
      assay systems. In conclusion, the crocin bleaching assay developed here is a
      simple, fast and economical screening assay and it will have great value in
      radioprotection programme for screening many potential compounds for
      radioprotection.

PMID- 22989746
TI  - The Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl)
      homoserine lactone enhances keratinocyte migration and induces Mmp13 gene
      expression in vitro.
AB  - Re-epithelialization is an essential step of wound healing involving three
      overlapping keratinocyte functions: migration, proliferation and differentiation.
      While quorum sensing (QS) is a cell density-dependent signaling system that
      enables bacteria to regulate the expression of certain genes, the QS molecule N
      (3-oxododecanoyl) homoserine lactone (AHL) exerts effects also on mammalian cells
      in a process called inter-kingdom signaling. Recent studies have shown that AHL
      improves epithelialization in in vivo wound healing models but detailed
      understanding of the molecular and cellular mechanisms are needed. The present
      study focused on the AHL as a candidate reagent to improve wound healing through
      direct modulation of keratinocyte's activity in the re-epithelialization process.
      Results indicated that AHL enhances the keratinocyte's ability to migrate in an
      in vitro scratch wound healing model probably due to the high Mmp13 gene
      expression analysis after AHL treatment that was revealed by real-time RT-PCR.
      Inhibition of activator protein 1 (AP-1) signaling pathway completely prevented
      the migration of keratinocytes, and also resulted in a diminished Mmp13 gene
      expression, suggesting that AP-1 might be essential in the AHL-induced migration.
      Taken together, these results imply that AHL is a promising candidate molecule to
      improve re-epithelialization through the induction of migration of keratinocytes.
      Further investigation is needed to clarify the mechanism of action and molecular
      pathway of AHL on the keratinocyte migration process.

PMID- 22989747
TI  - Membrane interaction and secondary structure of de novo designed arginine-and
      tryptophan peptides with dual function.
AB  - Cell-penetrating peptides and antimicrobial peptides are two classes of
      positively charged membrane active peptides with several properties in common.
      The challenge is to combine knowledge about the membrane interaction mechanisms
      and structural properties of the two classes to design peptides with membrane
      specific actions, useful either as transporters of cargo or as antibacterial
      substances. Membrane active peptides are commonly rich in arginine and
      tryptophan. We have previously designed a series of arg/trp peptides and
      investigated how the position and number of tryptophans affect cellular uptake.
      Here we explore the antimicrobial properties and the interaction with lipid model
      membranes of these peptides, using minimal inhibitory concentrations assay (MIC),
      circular dichroism (CD) and linear dichroism (LD). The results show that the
      arg/trp peptides inhibit the growth of the two gram positive strains
      Staphylococcus aureus and Staphylococcus pyogenes, with some individual
      variations depending on the position of the tryptophans. No inhibition of the
      gram negative strains Proteus mirabilis or Pseudomonas aeruginosa was noticed. CD
      indicated that when bound to lipid vesicles one of the peptides forms an alpha
      helical like structure, whereas the other five exhibited rather random coiled
      structures. LD indicated that all six peptides were somehow aligned parallel with
      the membrane surface. Our results do not reveal any obvious connection between
      membrane interaction and antimicrobial effect for the studied peptides. By
      contrast cell-penetrating properties can be coupled to both the secondary
      structure and the degree of order of the peptides.

PMID- 22989748
TI  - Recombinant expression of TLR5 proteins by ligand supplementation and a leucine
      rich repeat hybrid technique.
AB  - Vertebrate TLR5 directly binds bacterial flagellin proteins and activates innate
      immune responses against pathogenic flagellated bacteria. Structural and
      biochemical studies on the TLR5/flagellin interaction have been challenging due
      to the technical difficulty in obtaining active recombinant proteins of TLR5
      ectodomain (TLR5-ECD). We recently succeeded in production of the N-terminal
      leucine rich repeats (LRRs) of Danio rerio (dr) TLR5-ECD in a hybrid with another
      LRR protein, hagfish variable lymphocyte receptor (VLR), and determined the
      crystal structure of its complex with flagellin D1-D2-D3 domains. Although the
      structure provides valuable information about the interaction, it remains to be
      revealed how the C-terminal region of TLR5-ECD contributes to the interaction.
      Here, we present two methods to obtain recombinant TLR5 proteins that contain the
      C-terminal region in a baculovirus expression system. First, production of
      biologically active full-length drTLR5-ECD was substantially enhanced by
      supplementation of expression culture with purified flagellin proteins. Second,
      we designed TLR5-VLR hybrids using an LRR hybrid technology by single and double
      LRR fusions and were able to express diverse regions of drTLR5-ECD, allowing us
      to detect a previously unidentified TLR5/flagellin interaction. The drTLR5-VLR
      hybrid technique was also successfully applied to human TLR5-ECD whose expression
      has been highly problematic. These alternative TLR5 expression strategies provide
      an opportunity to obtain a complete view of the TLR5/flagellin interaction and
      can be applied to other LRR proteins.

PMID- 22989749
TI  - MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR
      expression in vascular endothelial cells.
AB  - Shear stress associated with blood flow plays an important role in regulating
      gene expression and cell function in endothelial cells (ECs). MicroRNAs (miRNAs)
      are highly conserved, small non-coding RNAs that negatively regulate the
      expression of target genes by binding to the mRNA 3'-untranslated region (3'UTR)
      at the posttranscriptional level involved in diverse cellular processes. This
      study demonstrates that microRNA-101 in response to laminar shear stress (LSS) is
      involved in the flow regulation of gene expression in ECs. qRT-PCR analysis
      showed that miR-101 expression was significantly upregulated in human umbilical
      vein endothelial cells (HUVECs) exposed to 12 dyn/cm(2) laminar shear stress for
      12h. We found that transfection of miR-101 significantly decreased the luciferase
      activity of plasmid reporter containing the 3'UTR of mammalian target of
      rapamycin (mTOR) gene. Western analysis revealed that the protein level of mTOR
      was significantly reduced in ECs transfected with miR-101. Furthermore, miR-101
      overexpression induced cell cycle arrest at the G1/S transition and suppressed
      endothelial cell proliferation. Finally, transfection of miR-101 inhibitors
      attenuated the suppressive effects of LSS on mTOR expression, which identified
      the efficacy of loss-of-function of miR-101 in laminar flow-treated ECs. In
      conclusion, we have demonstrated that upregulation of miR-101 in response to LSS
      contributes to the suppressive effects of LSS on mTOR expression and EC
      proliferation. These studies advance our understanding of the posttranscriptional
      mechanisms by which shear stress modulates endothelial homeostasis.

PMID- 22989750
TI  - Allele specific gain-of-function activity of p53 mutants in lung cancer cells.
AB  - p53 mutations are mostly single amino acid changes resulting in expression of a
      stable mutant protein with "gain of function" (GOF) activity having a dominant
      oncogenic role rather than simple loss of function of wild-type p53. Knock-down
      of mutant p53 in human lung cancer cell lines with different endogenous p53
      mutants results in loss of GOF activity as shown by lowering of cell growth rate.
      Two lung cancer cell lines, ABC1 and H1437, carrying endogenous mutants p53-P278S
      and -R267P, show reduction in growth rate on knock-down on p53 levels. However,
      whereas reduction of the p53 level induces loss of tumorigenicity in nude mice
      for ABC1 cells, it escalates tumorigenicity for H1437 cells. We have tested their
      transactivation potential on p53 target gene promoters by performing transient
      transcriptional assays in the p53-null H1299 lung cancer cell line.
      Interestingly, while the mutant p53 target promoter Axl was activated by both the
      mutants, the p21 promoter was activated by p53-R267P and wild-type p53 but not by
      p53-P278S; showing a clear difference in transcriptional activity between the two
      mutants. Our results demonstrate allele specificity between GOF p53 mutants and
      attempt to show that the specificity is dependent on the transactivation property
      of GOF p53; it also suggests importance of p21 activation in tumor suppression by
      p53.

PMID- 22989751
TI  - Letter to the Editor on "Synthetic cyclohexenyl chalcone natural products possess
      cytotoxic activities against prostate cancer cells and inhibit cysteine
      cathepsins in vitro".

PMID- 22989753
TI  - Novel ATPase activity of the polyprotein intermediate, Viral Protein genome
      linked-Nuclear Inclusion-a protease, of Pepper vein banding potyvirus.
AB  - Potyviruses temporally regulate their protein function by polyprotein processing.
      Previous studies have shown that VPg (Viral Protein genome-linked) of Pepper vein
      banding virus interacts with the NIa-Pro (Nuclear Inclusion-a protease) domain,
      and modulates the kinetics of the protease. In the present study, we report for
      the first time that VPg harbors the Walker motifs A and B, and the presence of
      NIa-Pro, especially in cis (cleavage site (E191A) VPg-Pro mutant), is essential
      for manifestation of the ATPase activity. Mutation of Lys47 (Walker motif A) and
      Asp88:Glu89 (Walker motif B) to alanine in E191A VPg-Pro lead to reduced ATPase
      activity, confirming that this activity was inherent to VPg. We propose that
      potyviral VPg, established as an intrinsically disordered domain, undergoes
      plausible structural alterations upon interaction with globular NIa-Pro which
      induces the ATPase activity.

PMID- 22989752
TI  - Involvement of calmodulin and calmodulin kinase II in tumor necrosis factor alpha
      induced survival of bone marrow derived macrophages.
AB  - We previously showed that survival signaling in TNFalpha-treated, human THP1
      derived macrophages (TDMs) has an obligatory requirement for constitutive Ca(2+)
      influx through a mechanism involving calmodulin/calmodulin kinase II
      (CAM/CAMKII). We also demonstrated that such requirement also applies to the
      protective actions of TNFalpha in murine bone marrow-derived macrophages (BMDMs)
      and that TRPC3 channels mediate constitutive Ca(2+) influx. Using a
      pharmacological approach we here examined if in BMDMs, similarly to TDMs,
      TNFalpha-induced survival signaling also involves CAM/CAMKII. In BMDMs, TNFalpha
      induced rapid activation of the survival pathways NFkappaB, AKT and p38MAPK. All
      these routes were activated in a PI3K-dependent fashion. Activation of AKT and
      NFkappaB, but not that of p38MAPK, was abrogated by the CAM inhibitor W7, while
      KN-62, a CAMKII inhibitor, prevented activation of AKT and p38MAPK but not that
      of NFkappaB. Inhibition of CAM or CAMKII completely prevented the protective
      actions of TNFalpha. Our observations indicate that in BMDMs CAM and CAMKII have
      differential contributions to the components of TNFalpha-dependent survival
      signaling and underscore a complex interplay among canonical survival routes.
      These findings set a signaling framework to understand how constitutive Ca(2+)
      influx couples to macrophage survival in BMDMs.

PMID- 22989754
TI  - Anti-tumor effects of an engineered "killer" transfer RNA.
AB  - A hallmark of cancer cells is their ability to continuously divide; and rapid
      proliferation requires increased protein translation. Elevating levels of
      misfolded proteins can elicit growth arrest due to ER stress and decreased global
      translation. Failure to correct prolonged ER stress eventually results in cell
      death via apoptosis. tRNA(Ser)(AAU) is an engineered human tRNA(Ser) with an
      anticodon coding for isoleucine. Here we test the possibility that tRNA(Ser)(AAU)
      can be an effective killing agent of breast cancer cells and can effectively
      inhibit tumor-formation in mice. We found that tRNA(Ser)(AAU) exert strong
      effects on breast cancer translation activity, cell viability, and tumor
      formation. Translation is strongly inhibited by tRNA(Ser)(AAU) in both
      tumorigenic and non-tumorigenic cells. tRNA(Ser)(AAU) significantly decreased the
      number of viable cells over time. A short time treatment with tRNA(Ser)(AAU) was
      sufficient to eliminate breast tumor formation in a xenograft mouse model. Our
      results indicate that tRNA(Ser)(AAU) can inhibit breast cancer metabolism, growth
      and tumor formation. This RNA has strong anti-cancer effects and presents an
      opportunity for its development into an anti-tumor agent. Because tRNA(Ser)(AAU)
      corrupts the protein synthesis mechanism that is an integral component of the
      cell, it would be extremely difficult for tumor cells to evolve and develop
      resistance against this anti-tumor agent.

PMID- 22989755
TI  - TGFbeta1 induces apoptosis in invasive prostate cancer and bladder cancer cells
      via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases.
AB  - Recent findings indicate that advanced stage cancers shun the tumor suppressive
      actions of TGFbeta and inexplicably utilize the cytokine as a tumor promoter. We
      investigated the effect of TGFbeta1 on the survival and proliferation of invasive
      prostate (PC3) and bladder (T24) cancer cells. Our study indicated that TGFbeta1
      decreased cell viability and induced apoptosis in invasive human PC3 and T24
      cells via activation of p38 MAPK-JNK-Caspase9/8/3 pathway. Surprisingly, no
      change in the phosphorylation of pro-survival Akt kinase was observed. We
      postulate that TGFbeta1 pathway may be utilized for specifically targeting
      urological cancers without inflicting side effects on normal tissues.

PMID- 22989756
TI  - RNA interference regulates the cell cycle checkpoint through the RNA export
      factor, Ptr1, in fission yeast.
AB  - Ago1, an effector protein of RNA interference (RNAi), regulates heterochromatin
      silencing and cell cycle arrest in fission yeast. However, the mechanism by which
      Ago1 controls cell cycle checkpoint following hydroxyurea (HU) treatment has not
      been elucidated. In this study, we show that Ago1 and other RNAi factors control
      cell cycle checkpoint following HU treatment via a mechanism independent of
      silencing. While silencing requires dcr1(+), the overexpression of ago1(+)
      alleviated the cell cycle defect in dcr1Delta. Ago1 interacted with the mRNA
      export factor, Ptr1. The ptr1-1 mutation impaired cell cycle checkpoint but gene
      silencing was unaffected. Genetic analysis revealed that the regulation of cell
      cycle checkpoint by ago1(+) is dependent on ptr1(+). Nuclear accumulation of
      poly(A)(+) RNAs was detected in mutants of ago1(+) and ptr1(+), suggesting there
      is a functional link between the cell cycle checkpoint and RNAi-mediated RNA
      quality control.

PMID- 22989757
TI  - The development of novel HIV integrase inhibitors and the problem of drug
      resistance.
AB  - Although all HIV drugs developed to date are prone to the problem of drug
      resistance, there is hope that second generation integrase inhibitors may prove
      to be relatively resilient to this problem and to retain efficacy over long
      periods. This review summarizes information about the integrase mutations
      identified to date and about why the most recently developed members of this drug
      class may be superior to earlier drugs. Several newly identified resistance
      mutations, such as G118R, R263K and S153Y, have been identified through tissue
      culture selection studies with second-generation integrase strand-transfer
      inhibitors (INSTIs). These new mutations add to our understanding of the three
      previously identified resistance pathways involving mutations at positions Y143,
      N155 and Q148. Biochemical analyses structural modeling, and deep sequencing are
      methods that currently help in the understanding of the mechanisms of resistance
      conferred by these various substitutions. Despite the fact that these new
      resistance mutations confer only low-level cross-resistance to second-generation
      drugs, the Q148 pathway with numerous secondary mutations has the potential to
      significantly decrease susceptibility to all members of the INSTI family of
      drugs. Selection of mutations in vitro with second-generation INSTIs suggests
      that only low level cross-resistance may exist between these new drugs and first
      generation members of this class. The emergence of mutations at position Q148
      should be monitored whenever possible and more data are needed to assess the long
      term efficacy of second-generation INSTIs in patients who may have failed older
      INSTIs such as elvitegravir and raltegravir.

PMID- 22989758
TI  - The first synthesis of Krempene B.
AB  - The synthesis of Krempene B, which can be isolated from the marine soft coral
      Cladiella krempfi, is achieved in 23.9% overall yield from commercially available
      3beta-acetoxy-5-pregnen-20-one by 11 steps. Key transformations include the
      dienone-phenol rearrangement of steroids and Wittig reaction.

PMID- 22989759
TI  - Isolation of an Eimeria ninakohlyakimovae field strain (Canary Islands) and
      analysis of its infection characteristics in goat kids.
AB  - The current study was conducted to isolate a field strain of Eimeria
      ninakohlyakimovae, characterize its infectivity and the response to challenge
      under experimental conditions. The isolated strain (GC) induced a prepatent
      period of 14-15 days p.i., a patency of 7+/-2 days and a noticeable pathogenicity
      in infected goat kids. Challenge trials resulting in a decrease of oocysts per
      gram counts as well as a milder intensity of clinical signs in re-infected
      animals indicated the capacity of this strain to induce protective immune
      response. Altogether, the data reported in the present study suggest that the
      strain E. ninakohlyakimovae GC is a useful tool for the investigation of
      mechanisms of pathogenicity as well as host protective immune response in caprine
      coccidiosis, representing a valuable prerequisite for the development of future
      strategies in prophylaxis and control of this important parasitic disease in
      goat.

PMID- 22989760
TI  - Comparative clonal analysis of reconstitution kinetics after transplantation of
      hematopoietic stem cells gene marked with a lentiviral SIN or a gamma-retroviral
      LTR vector.
AB  - Retroviral gene marking has been used successfully in preclinical and clinical
      transplantation settings. Highly sensitive techniques for vector insertion-site
      determination, such as linear amplification-mediated polymerase chain reaction
      (LAM-PCR) in conjunction with next-generation sequencing, have been introduced to
      assess the composition of gene-marked hematopoiesis at a single-cell level. Here
      we used these novel techniques for directly comparing clonal reconstitution
      kinetics in mice transplanted with bone-marrow-derived stem cells genetically
      marked with either a standard, spleen focus-forming virus long terminal repeat
      (LTR)-driven gamma-retroviral, or a lentiviral self-inactivating vector
      containing an identical but internal spleen focus-forming virus-derived
      enhancer/promoter. We observed that the use of the lentiviral self-inactivating
      vector for gene marking was associated with a broader repertoire of differently
      marked hematopoietic clones. More importantly, we found a significantly higher
      probability of insertions in growth-promoting, clonal-dominance-associated genes
      in the spleen focus-forming virus LTR-driven gamma-retroviral vector at later
      time points of analysis. Based on our data, we suggest that the combined use of
      LAM-PCR and next-generation sequencing represents a potent tool for the analysis
      of clonal reconstitution kinetics in the context of gene marking with integrated
      vectors. At the same time, our findings prove that the use of multiple
      restriction enzymes for LAM-PCR is indispensable to detect most or ideally all
      individual stem cell clones contributing to hematopoiesis. We have also found
      that techniques such as quantitative PCR can be helpful to retrospectively
      analyze reconstitution kinetics for individual hematopoietic stem cell clones.
      Finally, our results confirm the notion that marking with lentiviral self
      inactivating vectors is associated with a lower risk of genotoxicity as compared
      with gamma-retroviral LTR vectors.

PMID- 22989762
TI  - The impact of quasispecies dynamics on the use of therapeutics.
AB  - The application of quasispecies theory to viral populations has boosted our
      understanding of how endogenous and exogenous features condition their
      adaptation. Mounting empirical evidence demonstrates that internal interactions
      within mutant spectra may cause unexpected responses to antiviral treatments. In
      this scenario, increased mutagenesis could be efficient at low mutagen doses due
      to the lethal action of defective genomes, whereas sequential administration of
      antiviral drugs might be superior to combination therapies. Our ability to
      predict the outcome of a particular therapy takes advantage of the complementary
      use of in vivo observations, in vitro experiments, and mathematical models.

PMID- 22989761
TI  - Sca-1 is an early-response target of histone deacetylase inhibitors and marks
      hematopoietic cells with enhanced function.
AB  - Histone deacetylase inhibitors (HDIs) have been shown to enhance hematopoietic
      stem and progenitor cell activity and improve stem cell outcomes after ex vivo
      culture. Identification of gene targets of HDIs is required to understand the
      full potential of these compounds and can allow for improved stem cell culturing
      protocols. The molecular process that underlies the biological effects of
      valproic acid (VPA), a widely used HDI, on hematopoietic stem/progenitor cells
      was investigated by studying the early-response genes of VPA. These genes were
      linked to VPA-induced enhancement of cell function as measured by in vitro
      assays. Genome-wide gene expression studies revealed over-representation of genes
      involved in glutathione metabolism, receptor and signal transducer activity, and
      changes in the hematopoietic stem/progenitor cells surface profile after short,
      24-hour VPA treatment. Sca-1, a well-known and widely used stem cell surface
      marker, was identified as a prominent VPA target. We showed that multiple HDIs
      induce Sca-1 expression on hematopoietic cells. VPA strongly preserved Sca-1
      expression on Lin(-)Sca1(+)ckit(+) cells, but also reactivated Sca-1 on committed
      progenitor cells that were Sca-1(neg), thereby reverting them to the Lin(
      )Sca1(+)ckit(+) phenotype. We demonstrated that reacquired Sca-1 expression
      coincided with induced self-renewal capacity as measured by in vitro replating
      assays, while Sca-1 itself was not required for the biological effects of VPA as
      demonstrated using Sca-1-deficient progenitor cells. In conclusion, our results
      show that VPA modulates several genes involved in multiple signal transduction
      pathways, of which Sca-1 was shown to mark cells with increased self-renewal
      capacity in response to HDIs.

PMID- 22989763
TI  - Comparison of peritonsillar infiltration of tramadol and lidocaine for the relief
      of post-tonsillectomy pain.
AB  - BACKGROUND: Several studies have reported the use of peritonsillar infiltrations
      of local anaesthetics and/or locally active analgesic drugs for the relief of
      post-tonsillectomy pain, with variable results in terms of quality and duration
      of analgesia. We aimed to compare the effects of peritonsillar infiltration of
      lidocaine versus tramadol versus placebo on post-tonsillectomy pain. METHODS:
      Sixty patients over the age of 10 years undergoing bilateral elective
      tonsillectomy under general anaesthesia were randomised into three groups. The
      first group received peritonsillar infiltration of tramadol, the second 2 per
      cent lidocaine and the third normal saline. In all groups, peritonsillar
      infiltration was carried out after tonsillectomy but prior to tracheal
      extubation. Post-operative comparisons were made to assess the quality of pain
      control and the patients' analgesic requirements. RESULTS: Peritonsillar
      infiltration of tramadol provided an analgesic effect comparable to that of
      lidocaine in the first 6 hours post-operation, as reflected by visual analogue
      scale pain scores and opioid requirements, which were lower compared with the
      placebo group. CONCLUSION: Peritonsillar infiltration of tramadol provided pain
      control in the first 6 hours post-tonsillectomy which was comparable to that of
      lidocaine.

PMID- 22989764
TI  - From pluripotency to islets: miRNAs as critical regulators of human cellular
      differentiation.
AB  - MicroRNAs (miRNAs) actively regulate differentiation as pluripotent cells become
      cells of pancreatic endocrine lineage, including insulin-producing beta cells.
      The process is dynamic; some miRNAs help maintain pluripotency, while others
      drive cell fate decisions. Here, we survey the current literature and describe
      the biological role of selected miRNAs in maintenance of both mouse and human
      embryonic stem cell (ESC) pluripotency. Subsequently, we review the increasing
      evidence that miRNAs act at selected points in differentiation to regulate
      decisions about early cell fate (definitive endoderm and mesoderm), formation of
      pancreatic precursor cells, endocrine cell function, as well as epithelial to
      mesenchymal transition.

PMID- 22989766
TI  - Exome sequencing and advances in crop improvement.
AB  - Next-generation sequencing strategies have opened new vistas for molecular plant
      breeding. The sequence information obtained by the advent of next-generation
      sequencing provides a valuable tool not only for improving domesticated crops but
      also for investigating the natural evolution of crops. Such information provides
      an enormous potential for sustainable agriculture. In this review, we discuss how
      such sequencing approaches have transformed exome sequencing into a practical
      utility that has enormous potential for crop improvement in agriculture.
      Furthermore, we also describe the future of crop improvement beyond the exome
      sequencing strategies.

PMID- 22989768
TI  - Purification and characterization of glutathione S-transferase from turkey liver
      and inhibition effects of some metal ions on enzyme activity.
AB  - The glutathione S-transferases (EC 2.5.1.18) were purified and characterized from
      turkey liver for the first time. The enzyme was purified 252.7-fold with a yield
      of 45%, with a specific activity of 164.31 U/mg from turkey liver. The purity of
      the enzyme was determined by SDS-PAGE and showed two bands nearly 26 kDa and 24
      kDa on the gel. The native molecular mass of the enzyme was found to be
      approximately 53 kDa by Sephadex G-100 gel filtration chromatography. Optimal pH,
      stable pH, optimal temperature, optimum ionic strength, K(m) and V(max) values
      for GSH and CDNB were also determined for the enzyme as 7.3, 8.5, 50  degrees C,
      600 mM, 0.154 mM, 0.380 mM, 1.803 EU/ml, and 2.125 EU/ml, respectively.
      Additionally, inhibitory effects of metal ions (Cu(2+), Hg(2+), Fe(2+), Zn(2+),
      Ag(+), Mg(2+), Ni(2+), and Mn(2+)) were examined the enzyme's activity in vitro
      by performing Lineweaver-Burk graphs and plotting activity% vs., respectively.

PMID- 22989769
TI  - WITHDRAWN: Subchronic 26-week oral (gavage) toxicity study of Xylo
      oligosaccharide in beagle dogs.
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- 22989765
TI  - The genetics of dystonias.
AB  - Dystonia has been defined as a syndrome of involuntary, sustained muscle
      contractions affecting one or more sites of the body, frequently causing twisting
      and repetitive movements or abnormal postures. Dystonia is also a clinical sign
      that can be the presenting or prominent manifestation of many neurodegenerative
      and neurometabolic disorders. Etiological categories include primary dystonia,
      secondary dystonia, heredodegenerative diseases with dystonia, and dystonia plus.
      Primary dystonia includes syndromes in which dystonia is the sole phenotypic
      manifestation with the exception that tremor can be present as well. Most primary
      dystonia begins in adults, and approximately 10% of probands report one or more
      affected family members. Many cases of childhood- and adolescent-onset dystonia
      are due to mutations in TOR1A and THAP1. Mutations in THAP1 and CIZ1 have been
      associated with sporadic and familial adult-onset dystonia. Although significant
      recent progress had been made in defining the genetic basis for most of the
      dystonia-plus and heredodegenerative diseases with dystonia, a major gap remains
      in understanding the genetic etiologies for most cases of adult-onset primary
      dystonia. Common themes in the cellular biology of dystonia include G1/S cell
      cycle control, monoaminergic neurotransmission, mitochondrial dysfunction, and
      the neuronal stress response.

PMID- 22989767
TI  - Applications of functional protein microarrays in basic and clinical research.
AB  - The protein microarray technology provides a versatile platform for
      characterization of hundreds of thousands of proteins in a highly parallel and
      high-throughput manner. It is viewed as a new tool that overcomes the limitation
      of DNA microarrays. On the basis of its application, protein microarrays fall
      into two major classes: analytical and functional protein microarrays. In
      addition, tissue or cell lysates can also be directly spotted on a slide to form
      the so-called "reverse-phase" protein microarray. In the last decade,
      applications of functional protein microarrays in particular have flourished in
      studying protein function and construction of networks and pathways. In this
      chapter, we will review the recent advancements in the protein microarray
      technology, followed by presenting a series of examples to illustrate the power
      and versatility of protein microarrays in both basic and clinical research. As a
      powerful technology platform, it would not be surprising if protein microarrays
      will become one of the leading technologies in proteomic and diagnostic fields in
      the next decade.

PMID- 22989770
TI  - Effects of pretreatment with etomidate, ketamine, phenytoin, and
      phenytoin/midazolam on acute, lethal cocaine toxicity.
AB  - OBJECTIVE: To evaluate the effects of etomidate, ketamine, phenytoin, and
      phenytoin/midazolam in a mouse model of acute cocaine toxicity. METHODS: We
      performed a randomized controlled study consisting of five groups (n = 25 each)
      of rats that received intraperitoneal injections of normal saline solution, 5
      mg/kg ketamine, 7.5 mg/kg etomidate, 40 mg/kg phenytoin, and 40 mg/kg phenytoin
      and 2 mg/kg midazolam 10 minutes before cocaine hydrochloride (105 mg/kg).
      Following cocaine administration, a blinded observer watched the animals for 30
      minutes to assess seizures (popcorn jumping, tonic-clonic activity, or loss of
      righting reflex), and lethality for 30 minutes. RESULTS: The number of animals
      with seizures was lower in the etomidate (60%), phenytoin (40%), and
      phenytoin/midazolam (40%) groups (P<0.001). The etomidate (24%) and
      phenytoin/midazolam (16%) treatments were most effective in preventing lethality
      (P<0.001). Conversely, compared to the vehicle group (72%), cocaine-induced
      lethality was higher in the ketamine (84%) and phenytoin (92%) groups. All
      treatments prolonged the time to seizure, but this effect was most pronounced in
      the etomidate and phenytoin/midazolam groups, which also had the longest average
      time to lethality. DISCUSSION: The present study provides the first experimental
      evidence supporting the use of etomidate to treat cocaine-induced seizures.
      Notably, ketamine and phenytoin were ineffective. Our findings suggest that
      premedication with etomidate, phenytoin, and phenytoin/midazolam reduced seizure
      activity in an acute cocaine toxicity mouse model.

PMID- 22989771
TI  - Mathematical modeling of vesicle drug delivery systems 2: targeted vesicle
      interactions with cells, tumors, and the body.
AB  - Vesicles have been studied for several years in their ability to deliver drugs.
      Mathematical models have much potential in reducing time and resources required
      to engineer optimal vesicles, and this review article summarizes these models
      that aid in understanding the ability of targeted vesicles to bind and
      internalize into cancer cells, diffuse into tumors, and distribute in the body.
      With regard to binding and internalization, radiolabeling and surface plasmon
      resonance experiments can be performed to determine optimal vesicle size and the
      number and type of ligands conjugated. Binding and internalization properties are
      also inputs into a mathematical model of vesicle diffusion into tumor spheroids,
      which highlights the importance of the vesicle diffusion coefficient and the
      binding affinity of the targeting ligand. Biodistribution of vesicles in the
      body, along with their half-life, can be predicted with compartmental models for
      pharmacokinetics that include the effect of targeting ligands, and these
      predictions can be used in conjunction with in vivo models to aid in the design
      of drug carriers. Mathematical models can prove to be very useful in drug carrier
      design, and our hope is that this review will encourage more investigators to
      combine modeling with quantitative experimentation in the field of vesicle-based
      drug delivery.

PMID- 22989773
TI  - C(16)-Ceramide-induced F-actin regulation stimulates mouse embryonic stem cell
      migration: involvement of N-WASP/Cdc42/Arp2/3 complex and cofilin-1/alpha
      actinin.
AB  - Ceramide, a major structural element in the cellular membrane, is a key
      regulatory factor in various cellular behaviors that are dependent on ceramide
      induced association of specific proteins. However, molecular mechanisms that
      regulate ceramide-induced embryonic stem cell (ESC) migration are still not well
      understood. Thus, we investigated the effect of ceramide on migration and its
      related signal pathways in mouse ESCs. Among ceramide species with different
      fatty acid chain lengths, C(16)-Cer increased migration of mouse ESCs in a dose-
      (>=1MUM) and time-dependent (>=8h) manners, as determined by the cell migration
      assay. C(16)-Cer (10MUM) increased protein-kinase C (PKC) phosphorylation.
      Subsequently, C(16)-Cer increased focal adhesion kinase (FAK) and Paxillin
      phosphorylation, which were inhibited by PKC inhibitor Bisindolylmaleimide I
      (1MUM). When we examined for the downstream signaling molecules, C(16)-Cer
      activated small G protein (Cdc42) and increased the formation of complex with
      Neural Wiskott-Aldrich Syndrome Protein (N-WASP)/Cdc42/Actin-Related Protein 2/3
      (Arp2/3). This complex formation was disrupted by FAK- and Paxillin-specific
      siRNAs. Furthermore, C(16)-Cer-induced increase of filamentous actin (F-actin)
      expression was inhibited by Cdc42-, N-WASP-, and Arp2/3-specific siRNAs,
      respectively. Indeed, C(16)-Cer increased cofilin-1/F-actin interaction or F
      actin/alpha-actinin-1 and alpha-actinin-4 interactions in the cytoskeleton
      compartment, which was reversed by Cdc42-specific siRNA. Finally, C(16)-Cer
      induced increase of cell migration was inhibited by knocking down each signal
      pathway-related molecules with siRNA or inhibitors. In conclusion, C(16)-Cer
      enhances mouse ESC migration through the regulation of PKC and FAK/Paxillin
      dependent N-WASP/Cdc42/Arp2/3 complex formation as well as through promoting the
      interaction between cofilin-1 or alpha-actinin-1/-4 and F-actin.

PMID- 22989774
TI  - Detectable organophosphorus pesticide exposure in the blood of Nebraska and Iowa
      residents measured by mass spectrometry of butyrylcholinesterase adducts.
AB  - The Centers for Disease Control and Prevention detected organophosphorus
      pesticide (OP) metabolites in the urine of 96% of Americans, for urine collected
      before the ban on nonagricultural use of OP in December 2001. It was not known
      whether exposure was to OP degradation products or to live OP. Our goal was to
      determine whether exposure was to live OP in the years 2001, 2003, and 2005. Our
      test for exposure was the presence of OP adducts on plasma butyrylcholinesterase
      (BChE) detected by mass spectrometry. We purified three lots of BChE from the
      pooled plasma of 600-800 individuals each, in the years 2001, 2003, and 2005.
      Blood donors were healthy adults living in Nebraska and Iowa, two agricultural
      states that grow corn and soybeans. The purified BChE was tested for the presence
      of OP adducts on serine 198 using MALDI-TOF/TOF mass spectrometry. Low levels of
      methoxyphosphate-labeled BChE were found. The amount of adducted BChE was highest
      (1%) in blood collected in the year 2001 and lowest (0.2%) in blood collected in
      the year 2005. A negative control sample of BChE purified from cord blood
      collected in the year 2012 had no detectable adducts. It was concluded that
      Nebraska and Iowa residents were exposed to very low levels of live, intact
      organophosphorus pesticides, and that exposure levels in the pooled samples
      declined after the year 2001.

PMID- 22989772
TI  - Yeast and cancer cells - common principles in lipid metabolism.
AB  - One of the paradigms in cancer pathogenesis is the requirement of a cell to
      undergo transformation from respiration to aerobic glycolysis - the Warburg
      effect - to become malignant. The demands of a rapidly proliferating cell for
      carbon metabolites for the synthesis of biomass, energy and redox equivalents,
      are fundamentally different from the requirements of a differentiated, quiescent
      cell, but it remains open whether this metabolic switch is a cause or a
      consequence of malignant transformation. One of the major requirements is the
      synthesis of lipids for membrane formation to allow for cell proliferation, cell
      cycle progression and cytokinesis. Enzymes involved in lipid metabolism were
      indeed found to play a major role in cancer cell proliferation, and most of these
      enzymes are conserved in the yeast, Saccharomyces cerevisiae. Most notably,
      cancer cell physiology and metabolic fluxes are very similar to those in the
      fermenting and rapidly proliferating yeast. Both types of cells display highly
      active pathways for the synthesis of fatty acids and their incorporation into
      complex lipids, and imbalances in synthesis or turnover of lipids affect growth
      and viability of both yeast and cancer cells. Thus, understanding lipid
      metabolism in S. cerevisiae during cell cycle progression and cell proliferation
      may complement recent efforts to understand the importance and fundamental
      regulatory mechanisms of these pathways in cancer.

PMID- 22989775
TI  - Aryl methylcarbamates: potency and selectivity towards wild-type and carbamate
      insensitive (G119S) Anopheles gambiae acetylcholinesterase, and toxicity to G3
      strain An. gambiae.
AB  - New carbamates that are highly selective for inhibition of Anopheles gambiae
      acetylcholinesterase (AChE) over the human enzyme might be useful in continuing
      efforts to limit malaria transmission. In this report we assessed 34 synthesized
      and commercial carbamates for their selectivity to inhibit the AChEs found in
      carbamate-susceptible (G3) and carbamate-resistant (Akron) An. gambiae, relative
      to human AChE. Excellent correspondence is seen between inhibition potencies
      measured with carbamate-susceptible mosquito homogenate and purified recombinant
      wild-type (WT) An. gambiae AChE (AgAChE). Similarly, excellent correspondence is
      seen between inhibition potencies measured with carbamate-resistant mosquito
      homogenate and purified recombinant G119S AgAChE, consistent with our earlier
      finding that the Akron strain carries the G119S mutation. Although high (100- to
      500-fold) WT An. gambiae vs human selectivity is observed for several compounds,
      none of the carbamates tested potently inhibits the G119S mutant enzyme. Finally,
      we describe a predictive model for WT An. gambiae tarsal contact toxicity of the
      carbamates that relies on inhibition potency, molecular volume, and polar surface
      area.

PMID- 22989776
TI  - Metastatic renal cell carcinoma presenting as gastric polyps: A case report and
      review of the literature.
AB  - INTRODUCTION: Renal cell carcinoma (RCC) accounts for approximately 3% of adult
      malignancies and is responsible for over 13,000 deaths in the U.S. annually. The
      fatalities are largely due to distant metastasis, with lung, liver, bone and
      brain being most commonly affected organs. Gastric metastasis from RCC is a rare
      event (less than 20 cases reported in the English language literature) and
      usually presents as a large, solitary mass or ulcer (average size of 4.8cm)
      resembling primary gastric cancer. Here we report the first case of metastatic
      RCC presenting as small gastric polyps. PRESENTATION OF CASE: The patient was a
      60-year-old African American woman with a history of clear cell RCC (pT1bNX). She
      underwent esophagogastroduodenoscopy and colonoscopy 5months after nephrectomy
      due to anemia. Two non-ulcerated, 0.6-cm benign-appearing polyps were found at
      the greater curvature of the gastric body, which were subsequently removed
      endoscopically. Unexpectedly, histopathologic examination of the gastric polyps
      revealed nested collections of vacuolated epithelioid cells in a background of
      delicate, arborizing vasculature, immediately beneath the congested and
      hyperplastic foveolar epithelium. A diagnosis of metastatic RCC was rendered
      after confirming the renal epithelial origin by immunohistochemical stains.
      DISCUSSION: Gastric metastasis from RCC usually presents as a large, solitary
      mass or ulcer, but it can be subtle and present as multiple, small benign
      appearing polyps. CONCLUSION: A careful follow up and thorough endoscopic and
      histopathologic examinations should be conducted in patients with a history of
      RCC who present with gastrointestinal manifestations.

PMID- 22989777
TI  - Ordering and dynamics of the central tetrahedron in the 1/1 Zn6Sc periodic
      approximant to quasicrystal.
AB  - Periodic approximants to quasicrystals offer a unique opportunity to better
      understand the structure, physical properties and stabilizing mechanisms of their
      quasicrystal counterparts. We present a detailed study of the order-disorder
      phase transition occurring at about 160 K in the Zn(6)Sc cubic approximant to the
      icosahedral quasicrystal i-MgZnSc. This transition goes along with an anti
      parallel ordering of the tetrahedra located at the centres of large atomic
      clusters, which are packed on a bcc lattice. Single crystal x-ray diffuse
      scattering shows that the tetrahedra display pre-transitional short range
      ordering above T(c) (Yamada et al 2012 in preparation). Using quasielastic
      neutron scattering (QENS) we clearly evidence this short range order to be
      dynamical in nature above T(c). The QENS data are consistent with a model of
      tetrahedra 'jumping' between almost equivalent positions, which is supported by
      molecular dynamics simulations. This demonstrates a unique dynamical flexibility
      of the Zn(6)Sc structure even at room temperature.

PMID- 22989778
TI  - Intracranial atheromatous disease treatment with the Wingspan stent system:
      evaluation of clinical, procedural outcome and restenosis rate in a single-center
      series of 21 consecutive patients with acute and mid-term results.
AB  - BACKGROUND: Intracranial atherosclerosis may be the underlying pathology in up to
      15% of ischemic strokes, but may account for about 40% of strokes in some
      populations. After an ischemic event determined by intracranial atherosclerosis,
      patients have a 12% annual risk of stroke recurrence, mostly during the first
      year. OBJECTIVE: To evaluate procedural safety, clinical outcome and restenosis
      rate of Wingspan stent placement. METHODS: Twenty-one caucasoid patients were
      enrolled. Target patients were affected by high-grade, symptomatic, intracranial
      atherosclerotic lesions, were on antithrombotic therapy and at high stroke risk.
      All patients were treated with the Wingspan stent system. RESULTS: Technical
      success resulted 100%, with all target lesions being reduced to <50%. No stroke
      or death were observed at 30. The mean percent of stenosis was reduced from a
      middle value of 84% to a middle value of 17% after stent placement. Medium follow
      up was 19.5months (range 6-36months). No stroke or death occurred in any patient.
      None of the patients presented a <50% stent patency rate at follow-up.
      CONCLUSIONS: The short-term results and follow up analysis provide evidence
      demonstrating the safety of the Wingspan system when used in high-risk patient
      population. Due to concerns regarding long-term stent patency and ischemic events
      occurrence emerged from clinical trials such as the SAMMPRIS, intracranial
      angioplasty and stent with the Wingspan system should be considered only for high
      risk patients in which it may be considered the only viable therapeutic option.

PMID- 22989779
TI  - Reversible CT perfusion abnormalities in patient with migraine variant: a two
      phase process.

PMID- 22989780
TI  - Atrial fibrillation predicts good functional outcome following intravenous tissue
      plasminogen activator in patients with severe stroke.
AB  - OBJECTIVE: Atrial fibrillation (AF) is associated with poor outcome after
      intravenous thrombolysis probably due to greater pretreatment stroke severity. We
      conducted this retrospective study to determine whether AF is an independent
      predictor for clinical outcome in patients stratified by initial stroke severity.
      METHODS: A total of 143 acute ischemic stroke patients who received intravenous
      thrombolysis within 3h after onset were enrolled. The patients were categorized
      according to the baseline stroke severity by National Institute of Health Stroke
      Scale (NIHSS) score (<=10 vs. >10) and the presence of AF or not. Favorable 90
      day outcome was defined as a modified Rankin Scale (mRS) score<2. RESULTS: Among
      the 100 patients with severe stroke (NIHSS>10), those with AF (n=52) had a higher
      proportion of favorable 90-day outcome than those without AF (31% vs. 8%,
      P=0.005). After adjustment for age, baseline glucose level, and onset to
      treatment time, the difference remained significant (odds ratio 5.80, 95%
      confidence interval 1.63-20.68). In patients with mild stroke (NIHSS<=10), no
      difference in clinical outcome was found between AF (n=20) and non-AF (n=23)
      groups. CONCLUSION: Presence of AF was associated with favorable 90-day outcome
      following intravenous thrombolysis in patients with severe stroke at baseline,
      while the association did not exist in patients with mild stroke.

PMID- 22989781
TI  - [Hereditary optic neuropathies].
AB  - Hereditary optic neuropathies are a group of heterogeneous conditions affecting
      both optic nerves, with an autosomal dominant, autosomal recessive, X-related or
      mitochondrial transmission. The two most common non-syndromic hereditary optic
      neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic
      atrophy) are very different in their clinical presentation and their genetic
      transmission, leading however to a common, non-specific optic nerve atrophy.
      Beyond the optic atrophy-related visual loss, which is the clinical hallmark of
      this group of diseases, other associated neurological signs are increasingly
      recognized.

PMID- 22989782
TI  - [Diagnosis of psychocognitive complaints or disorders after de novo consultation
      in a university hospital specialized memory unit].
AB  - Psychiatric diagnoses are frequent in memory units, but most neurologists do not
      feel comfortable about making the diagnosis of psychopathologic cognitive
      complaint or disorder. The full diagnosis usually requires careful history taking
      and a neuropsychological examination followed by a clear joint explanation to the
      patient. There are no good validated clinical signs to distinguish organic memory
      complaints from psychological disorders, but a nonorganic pattern, as seen in
      somatic conversion disorder, can be suggestive of a "cognitivoform" disorder.
      Cognitive doubt is a frequent symptom of anxiety. Bradypsychia is a frequent
      symptom of depression. We report 50 patients attending their first neurological
      memory consultation in university hospital for whom a de novo diagnosis of
      psychopathologic disorder was established on the basis of the clinical setting,
      observation, examination and neuropsychological tests. These psychopathologic
      disorders accounted for 40.3% of first-consultation diagnoses. In 76% of cases,
      the neuropsychological examination was normal. Nine subjects had mild cognitive
      impairment, concerning executive functions in six and several domains in three.
      Simulation with atypical neuropsychological pattern was distinguished in three
      patients. The diagnoses were:psychosis (n=9), traumatic stress (n=5), depression
      (n=7), anxiety or obsession/compulsion (n=13), hypochondria and "cognitivoform"
      disorders (n=13). In this study, few patients consulted with a known psychiatric
      diagnosis. Psychiatric co-morbidity was common. In the memory unit, listening
      carefully to ascertain the psychic, somatic and social situation of each
      individual patient appears to be as important as evaluating cognition. The
      neurologist can rule out organic disorders or an exaggeration of somatic symptoms
      and determine the precise etiology in order to build a rationale for treatment.
      The neurologist can also avert an overconsumption of complementary explorations.
      In conclusion, this study shows first that psychopathologic disorders are
      commonly encountered in a neurological memory unit, emphasizing the need for
      training for the neurologist and collaboration with a psychiatrist, and secondly
      that the role of the memory unit cannot be limited to the diagnosis of
      Alzheimer's disease.

PMID- 22989783
TI  - [Early diagnosis of Alzheimer's disease].
AB  - INTRODUCTION: Diagnosis of Alzheimer's disease (AD) remains difficult to
      establish, and can only be considered as certain thanks to anatomopathological
      evidence, or genetic mutations. Current diagnostic criteria rely on innovative
      imaging and biological tools, in order to detect pathological cues from very
      early stages, and with best sensibility and sensitivity. STATE OF ART: Advances
      in neuro-imaging enabled the development of different tools to help establishing
      the diagnosis, such as cerebral atrophy assessment on magnetic resonance imaging
      (MRI), and cerebral metabolism study on positron emission tomography (PET).
      Besides, the increasing use of in vivo biological markers, combined to clinical
      criteria, enables to discriminate patients from healthy controls at even earlier
      stages. This includes studies on tau and beta-amyloid proteins concentrations in
      the cerebrosinal fluid, and amyloid-specific radioligands uptake. Familial forms
      of Alzheimer represent a great model for studying early or even pre-symptomatic
      AD, as genetic analyses constitute a diagnosis of certainty, even though they
      usually evolve earlier and faster. PERSPECTIVES, CONCLUSION: Diagnostic tools are
      more and more numerous and performant. According to patients' clinical
      heterogeneity, it appears essential to associate different method to investigate,
      in order to make a diagnosis as early and as reliable as possible.

PMID- 22989784
TI  - [Prevention of multiple sclerosis: a realistic goal?].
AB  - Multiple sclerosis (MS) is the most frequent source of chronic neurological
      disability in Western countries, and its incidence and prevalence are increasing.
      However, it is possible to determine its prodromal phase and the radiological,
      biological and immunological endophenotypes that are present before the clinical
      onset of the disease, despite remaining unseen with the naked eye. In this
      context, greater knowledge of the aetiological factors, both genetic and
      environmental, may lead the way towards primary prevention strategies for MS in
      the near future.

PMID- 22989785
TI  - Induction of CXCL10 chemokine in adrenocortical cells by stimulation through toll
      like receptor 3.
AB  - Addison's disease is a prototypic organ-specific autoimmune disease affecting the
      adrenal cortex. The CXC chemokine ligand 10 (CXCL10) is expressed early in viral
      infections, and is produced by primary adrenocortical cells stimulated by certain
      cytokines. CXCL10 is also elevated in the serum of Addison's disease patients. We
      therefore investigated if the viral RNA substitute polyinosine-polycytidylic acid
      (poly (I:C)) could influence the cytokine induced production of CXCL10 by
      adrenocortical cells. We found that poly (I:C) could induce CXCL10 in NCI-H295R
      adrenocortical carcinoma cells, either alone or synergistically along with
      cytokines interferon-gamma and tumor necrosis factor-alpha. This effect was found
      to be mediated by toll-like receptor 3 and both nuclear factor kappaB (NFkappaB)
      and signal transducer and activator of transcription-1 (STAT1), but not type I
      interferons, seemed to be involved. We propose that the combination of
      environmental and endogenous factors presented here, could contribute to the
      multifactorial pathogenesis of autoimmune Addison's disease.

PMID- 22989787
TI  - Marginal zone lymphoma of the thoracic dura causing spinal cord compression.
AB  - Primary extra-nodal marginal zone B cell lymphoma (Ex-MZBCL) or mucosa-associated
      lymphoid tissue (MALT) lymphoma of the cranial dura is a rare but well-known
      entity. We describe a 58-year-old woman with primary MALT lymphoma of the spinal
      dura causing extreme thickening of the dura and spinal cord compression who
      initially presented with acute spinal cord compression from a chronic epidural
      lesion. She was treated with surgery and radiotherapy and diagnosed with a mature
      B-cell lymphoma based on gene rearrangement studies. Two years following the
      completion of radiotherapy, she presented with an increase in the size of the
      residual mass that was suggestive of an epidural lesion. On re-exploration, no
      epidural lesion was found; however, the dura was extremely thickened causing
      spinal cord compression. Clinical course, histological evaluation, immunostaining
      and gene rearrangement studies resulted in a final diagnosis of primary Ex-MZBCL
      of the spinal dura. To our knowledge, this is the first report of Ex-MZBCL in the
      spinal dura. This diagnosis should be considered when evaluating spinal cord
      lesions in patients with primary central nervous system (CNS) lymphoma,
      especially recurrent lesions, since this group of tumors carries a favorable
      outcome compared to other primary CNS lymphomas.

PMID- 22989786
TI  - Extensive cortical involvement in leptomeningeal carcinomatosis.
AB  - We present a 77-year-old previously well patient with facial asymmetry and
      progressive weakness of the lower extremities. An initial MRI revealed slight
      contrast enhancement of the meninges. Three consecutive cerebrospinal fluid
      examinations demonstrated low glucose concentration, marked elevation of total
      protein and moderate pleocytosis. No tumor cells, fungi, acid-fast bacilli or
      mycobacterial DNA were found. The patient's level of consciousness deteriorated
      dramatically, and follow-up MRI showed widespread extensive cortical
      hyperintensities. The lesions showed restricted diffusion on diffusion-weighted
      images as well as low values on the corresponding apparent diffusion coefficient
      maps, the changes consistent with diffuse cytotoxic edema. Neuropathological
      examination findings were of leptomeningeal carcinomatosis (LMC) with diffuse
      continuous infiltration of the cerebral cortex, cerebellum and spinal cord. The
      autopsy revealed a subcentimetre adenocarcinoma of the lung. To our knowledge,
      this is the first report demonstrating extensive cortical involvement in
      adenocarcinomatous LMC.

PMID- 22989788
TI  - Mechanical thrombectomy in two patients using the Solitaire AB device in cerebral
      aneurysms during endovascular coil embolisation.
AB  - Two men, 52 years and 54 years of age, presented with subarachnoid haemorrhage as
      a result of ruptured cerebral aneurysms. Both patients were treated with
      endovascular coil embolisation. Thromboembolic complications occurred in the
      middle cerebral artery during the procedure, and local thrombectomy was performed
      for recanalisation. Digital subtraction angiography revealed the immediate
      restoration of flow after mechanical thrombectomy with a stent in both patients.
      The Solitaire AB stent (ev3, Plymouth, MN, USA) can rapidly, safely, and
      effectively retrieve clots from the middle cerebral artery during endovascular
      embolisation.

PMID- 22989789
TI  - Acute bilateral hearing loss as a "worsening sign" in a patient with critical
      basilar artery stenosis.
AB  - We report a patient who presented with an acute-onset transient vertigo and
      unsteady gait with bilateral hearing loss. Brain MRI revealed a critical basilar
      artery (BA) stenosis at the lower pons and infarction in various areas on both
      sides in the territories of the posterior inferior cerebellar arteries (PICA).
      Further, we could not visualize the right anterior inferior cerebellar artery
      (AICA). The bilateral hearing loss may be ascribed to stroke due to the critical
      BA stenosis, causing hypoperfusion injury extending from the PICA to the AICA on
      both sides. Local intra-arterial thrombolytic therapy with the administration of
      1*10(6) IU of urokinase aided partial recanalization of the BA, after which the
      right AICA reappeared. The neurological function of the patient recovered to
      normal, and no hemorrhagic complications were observed. Therefore, practitioners
      should be alert when treating patients with acute bilateral hearing loss, which
      may be related to an underlying catastrophic stroke.

PMID- 22989790
TI  - An anatomical analysis of the mini-modified orbitozygomatic and supra-orbital
      approaches.
AB  - Seven sides of cadaver heads were used to compare the surgical exposures provided
      by the mini-modified orbitozygomatic (MOz) and supra-orbital (SO) approaches. The
      Optotrak 3020 computerized tracking system (Northern Digital, Waterloo, ON,
      Canada) was utilized to evaluate the area of anatomical exposure defined by six
      points: (1) ipsilateral sphenoid ridge; (2) most distal point of the ipsilateral
      middle cerebral artery (MCA); (3) most distal point of the ipsilateral posterior
      cerebral artery (PCA); (4) most distal point of the contralateral PCA; (5) most
      distal point of the contralateral MCA; and (6) contralateral sphenoid ridge.
      Additionally, angles of approach for the ipsilateral MCA bifurcation, ipsilateral
      ICA bifurcation, basilar artery tip, contralateral MCA and ICA bifurcation and
      anterior communicating artery (AcomA) were evaluated, first for SO and then for
      MOz. An image guidance system was used to evaluate the limits of surgical
      exposure. No differences in the area of surgical exposure were noted (p>0.05).
      Vertical angles were significantly wider for the ipsilateral and contralateral
      ICA bifurcation, AcomA, contralateral MCA and basilar tip (p<0.05) for MOz. No
      differences in horizontal angles were observed between the approaches for the six
      targets (p>0.05). There were no differences in the limits of exposure. MOz
      affords no additional surgical working space. However, our results demonstrate
      systematically that vertical exposure is improved. The MOz should be performed
      while planning an approach to these regions and a wider exposure in the vertical
      axis is needed.

PMID- 22989791
TI  - Curvularia brain abscess.
AB  - Curvularia is a ubiquitous dematiaceous fungus that is a very rare but often
      fatal cause of infection in the central nervous system (CNS). In this report, we
      describe a patient with chronic sinusitis who presented with a Curvularia abscess
      of the skull base extending into the left frontal lobe. She was successfully
      treated with aggressive surgical resection and antibiotic therapy. In the
      published literature, this patient to our knowledge represents the longest period
      of disease-free follow-up in those afflicted with CNS Curvularia infection,
      indicating the importance of proper diagnosis and aggressive surgical debridement
      for a successful outcome.

PMID- 22989792
TI  - Complex partial status epilepticus associated with adult H1N1 infection.
AB  - In the wake of the worldwide H1N1 pandemic, there has been evidence that the H1N1
      influenza virus is associated with neurological complications. This is the first
      report describing status epilepticus in an adult patient with H1N1 virus
      infection, to our knowledge. This patient had no prior history of epilepsy and
      presented with complex partial status epilepticus. This was further illustrated
      on electroencephalographs and MRI brain changes that corresponded with the
      patient's clinical state and which subsequently resolved on follow-up. Although
      uncommon, H1N1 infections may result in central nervous system complications in
      adults and it is crucial to treat such patients with urgency.

PMID- 22989793
TI  - A voxel-based morphometric study of cortical gray matter volume changes in
      Alzheimer's disease with white matter hyperintensities.
AB  - White matter hyperintensity (WMH) is commonly detected in patients with
      Alzheimer's disease (AD), but its role in cortical impairment is unclear. This
      study investigated the effects of WMH on gray matter (GM) volume in patients with
      AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who
      underwent brain MRI and were then classified according to WMH grade, based on a
      combination of deep white matter hyperintensity (DWMH) and periventricular white
      matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel
      based morphometry. It was found that global GM volume decreased with increasing
      WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal
      gyri and insula (false discovery rate [FDR], p<0.01). After controlling for
      PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus
      (FDR, p<0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume
      reduction, especially in the frontal lobe, and DWMH is independently related to
      cortical atrophy.

PMID- 22989795
TI  - The impact of enrollment in clinical trials on survival of patients with
      glioblastoma.
AB  - The impact of enrollment in a clinical study on the survival of patients with
      glioblastoma has not been established. We retrospectively analyzed 564 patients
      with newly diagnosed glioblastoma treated between 1995 and 2008. They were
      divided into those enrolled in a clinical trial and randomized to a treatment or
      control arm, and those not enrolled and who received best standard of care (BSC).
      The three groups were matched for age and Karnofsky performance scale (KPS) score
      at presentation, and included only patients who underwent at least one tumor
      resection. Survival analysis was performed and multivariate Cox proportional
      hazards model and recursive partitioning analysis (RPA) identified predictors of
      survival. Following the matching process, 261 patients remained to form the final
      cohort. Of the 124 patients enrolled in a study, 81 (31.0%) were randomized to
      the treatment and 43 (16.5%) to the control arms. The overall median survival for
      the BSC (n=137), control, and treatment groups was 11.57 months (95% confidence
      interval [CI], 10.41-12.73), 16.27 months (95% CI, 14.10-18.43) and 16.10 months
      (95% CI, 14.34-17.86), respectively (p=0.002). Participation in a clinical trial,
      regardless of the arm, was a significant predictor of survival, as were age and
      KPS at diagnosis. The RPA also demonstrated a favorable impact of participation
      in a clinical trial. Additional tumor resections and various treatment modalities
      were administered with significantly higher frequency among patients enrolled in
      clinical studies. Thus, enrollment in a clinical study carried a significant
      survival advantage for patients with glioblastoma, raising practical and ethical
      issues regarding the quality of care of patients who receive "standard" therapy.

PMID- 22989794
TI  - Resolution of cervical syringomyelia after transoral odontoidectomy and
      occipitocervical fusion in a patient with basilar invagination and Type I Chiari
      malformation.
AB  - We present a 16-year-old male patient with Marfan's syndrome who presented with
      quadriparesis from a Type I Chiari malformation (CM) with basilar invagination
      and a syrinx. The condition resolved after transoral odontoidectomy and
      occipitocervical fusion without posterior decompression of the CM. Thus, ventral
      decompression alone can resolve a cervical syrinx in patients with compression of
      the foramen magnum.

PMID- 22989796
TI  - Drug eluting stents: current status and new developments.
AB  - Despite the favorable impact of drug eluting stents on stent restenosis, their
      long-term reliability is considered worrisome by some because of stent
      thrombosis. Often attributed to adverse reactions to the stent platform, both the
      drugs and polymer characteristics have been further advanced with current
      technologies. The present review discussed current drug eluting stents and new
      developments.

PMID- 22989797
TI  - Brain derived neurotrophic factor (BDNF) in cardiometabolic physiology and
      diseases.
AB  - Important advances in our understanding of the relationships between adipose
      tissue derived peptides, namely adipokines, and their effects on cardiovascular
      functions have been achieved in recent years. Growing knowledge of adipokine
      biology is revealing the complexity of these proteins. Adipose tissue releases
      some other proteins called neurotrophins that are mainly active in central and
      peripheral nervous system. However, secretion and activity of these hormones are
      not only limited to neuronal cells and tissues, but they also take part in
      adipose tissue development, energy metabolism, glucose utilization, insulin
      sensitivity, inflammation, lipoprotein synthesis, and atherosclerosis. In this
      review, we describe the most recent advances in the functions of brain derived
      nerve growth factor (BDNF), a major type of neurotrophins, focusing primarily on
      cardiovascular and metabolic diseases.

PMID- 22989798
TI  - Management of acute ischemic stroke occurred during thrombolytic treatment of a
      patient with prosthetic mitral valve thrombosis: continuing thrombolysis on top
      of thrombolysis.

PMID- 22989799
TI  - Starr-Edwards caged ball valve pursuing to astonish us-38 years in mitral
      position.

PMID- 22989800
TI  - Treatment of aortic valve stenosis and gastrointestinal bleeding by transcatheter
      aortic valve implantation in Heyde syndrome.

PMID- 22989801
TI  - Double covered stent closure of extracardiac Fontan multiple fenestrations.

PMID- 22989802
TI  - Acute aortic dissection in a 10-year-old boy with bicuspid aortic valve.

PMID- 22989803
TI  - Unconscious plagiarism and withdrawal of the manuscript under consideration.

PMID- 22989804
TI  - Heart block: Neither sweet nor bitter.

PMID- 22989805
TI  - Giant J-wave (Osborn wave) related to hypothermia and hypokalemia.

PMID- 22989806
TI  - Increased level of cardiac troponin-I due to rheumatoid factor positivity in a
      healthy patient with normal coronary arteries.

PMID- 22989807
TI  - Multilateral coronary fistulas terminating in the lung parenchyma.

PMID- 22989808
TI  - [Minimally invasive on-pump aortic valve replacement with thoracic epidural
      anesthesia].

PMID- 22989809
TI  - Knowledge and adherence to treatment in patients with poor or improved
      anticoagulation control.

PMID- 22989810
TI  - Mitral regurgitation secondary to mitral anterior leaflet rupture after mitral
      valvuloplasty.

PMID- 22989812
TI  - Incidentally diagnosed pseudoaneurysm of mitral-aortic intervalvular fibrosa.

PMID- 22989811
TI  - Incidental diagnosis of an aneurysm of the mitral valve posterior leaflet.

PMID- 22989813
TI  - 3D echocardiographic evaluation of ruptured pseudoaneurysm of the mitral-aortic
      intervalvular fibrosa.

PMID- 22989814
TI  - Cor triatriatum sinister demonstrated by 3D-transesophageal echocardiography.

PMID- 22989815
TI  - [Incidentally diagnosed unusual large epicardial adipose tissue].

PMID- 22989816
TI  - Very late diagnosed complication of coronary artery bypass surgery: coronary
      artery to right ventricular fistula.

PMID- 22989817
TI  - Severe inflammation in the background liver cirrhosis correlates with the
      development of poorly differentiated HCC in HCV-associated liver cirrhosis.
AB  - OBJECTIVE: Whether severe inflammation in the background liver cirrhosis might
      correlate with the development of poorly differentiated human hepatocellular
      carcinoma (HCC) was studied in hepatitis C virus (HCV)-associated liver
      cirrhosis. METHODS: Out of 214 HCC patients who underwent curative hepatic
      resection, 148 patients were HCV-associated liver cirrhosis (LC) patients. Out of
      these 148, 31 patients with small solitary HCC nodule (diameter <= 3 cm) were
      included in this study. Inflammation in the background LC was evaluated by
      modified histology activity index (HAI). To evaluate the inflammation, piece meal
      necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular
      inflammation (each 0-4) were estimated. In each case, the average HAI was
      calculated. The grade of malignancy of HCC was determined by World Health
      Organization (WHO) classification. RESULTS: The average HAI score in the
      cirrhotic portion in 17 patients with poorly differentiated HCC (5.21 +/- 1.15,
      mean +/- standard deviation (SD)) was significantly larger than that in 14
      patients without poorly differentiated HCC (4.05 +/- 0.83, p<0.005). The
      occurrence rate of HCC containing poorly differentiated HCC component in the
      patients whose HAI was more than 5.0 was 80.0% (12 out of 15), and was
      significantly higher compared with those in patients whose HAI was less than 5.0
      (5 out of 16, 31.3%, p<0.025). In univariate and multivariate analyses for
      contribution to poorly differentiated HCC development, HAI was the only
      significant contributor (p=0.011, p=0.012 respectively). CONCLUSION: It is
      suggested that severe inflammation in the background cirrhosis accelerates the
      promotion in the HCC development from HCV-associated LC.

PMID- 22989818
TI  - Omega-3 fatty acids in the prevention of atrial fibrillation recurrences after
      cardioversion: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Previous randomized studies have reported conflicting results on the
      efficacy of omega-3 fatty acids in preventing atrial fibrillation (AF)
      recurrences after cardioversion. OBJECTIVE: A systematic review and meta-analysis
      of the role of omega-3 fatty acids in the prevention of atrial fibrillation
      recurrences after cardioversion was conducted. METHODS: PubMed, Cochrane Library,
      Elsevier, Science Online database were searched up to the end of January 2012 to
      identify all of the studies in human subjects that reported the effects of omega
      3 fatty acids on the prevention of atrial fibrillation recurrences after
      cardioversion. RESULTS: Overall, omega-3 fatty acids had no significant effect on
      the prevention of AF recurrences after cardioversion (OR: 0.63,95% CI 0.35-1.13;
      p=0.12). The heterogeneity among the studies was significant (p=0.01, I(2)=66%).
      Subgroup analysis showed that by administering omega-3 fatty acids at least 4
      weeks prior to cardioversion and continuing thereafter, the recurrence rate of AF
      is significantly low (OR: 0.39, 95% CI 0.25-0.61; p<0.0001). CONCLUSION: In the
      subgroup administered omega-3 fatty acids at least 4 weeks prior to cardioversion
      and continued thereafter, the recurrence rate of AF was significantly low. More
      double-blind, randomized, placebo-controlled, multicenter studies with high
      quality and longer follow-up periods are needed to affirm our conclusion.

PMID- 22989819
TI  - Effects of combined antihypertensive therapy with losartan/hydrochlorothiazide on
      uric acid metabolism.
AB  - OBJECTIVE: The Jikei Optimal Antihypertensive Treatment (JOINT) study originally
      evaluated the effect of a fixed-dose formulation of losartan (LOS) (50 mg) plus
      12.5 hydrochrolthiazide (HCTZ) for achieving better blood pressure (BP) control
      in patients with uncontrolled hypertension. This study is a sub-analysis of the
      JOINT study, focusing on the effect of LOS/HCTZ on the uric acid (UA) metabolism.
      METHODS: Among 228 participants in the JOINT study, a total of 164 patients whose
      blood and urinary UA specimens were available were included in the present
      analyses. RESULTS: Six months after switching from the prior antihypertensive
      agent(s) to a single tablet formulation of LOS/HCTZ, the overall serum UA
      concentration (sUA) increased from 6.0 +/- 1.6 mg/dL to 6.2 +/- 1.6 mg/dL
      (p=0.029). The urinary UA/creatinine (Cr) ratio increased from 0.45 +/- 0.21 to
      0.50 +/- 0.25 (p=0.014), and the fractional excretion of UA (FEUA) also
      increased, from 7.1 +/- 3.6 to 7.0 +/- 4.3, p=0.04). Multivariate regression
      analyses of the basal parameters showed the change in sUA (DeltaUA) to correlate
      with the basal sUA (beta=-0.483, p<0.001), estimated glomerular filtration rate
      (eGFR) (beta=-0.202, p=0.007) and systolic BP (beta=0.147, p=0.038). In addition,
      the DeltaUA also correlated with the changes in the estimated glomerular
      filtration rate (DeltaeGFR) (beta=-0.332, p<0.001). When the patients were
      classified into two groups depending on their basal sUA, those with a basal sUA
      >= 7 mg/dL exhibited a decrease in their sUA, whereas the rest of those with a
      sUA <7 mg/dL experienced an increase. Furthermore, patients who had previously
      been treated with LOS alone had a greater increase in the sUA than those treated
      with an angiotensin II blocker (ARB) other than LOS alone. CONCLUSION:
      Antihypertensive therapy with a single tablet formulation of LOS/HCTZ is
      considered to be a useful option for controlling both BP and sUA, especially in
      uncontrolled hypertensive patients with hyperuricemia.

PMID- 22989820
TI  - Removal of tracheobronchial foreign bodies in adults using a flexible
      bronchoscope: experience with 200 cases in China.
AB  - OBJECTIVE: Tracheobronchial foreign bodies (FBs) are frequently present in
      adults. This study reports our experience with the managements of FB and FB
      related complications using flexible bronchoscopy. METHODS: We retrospectively
      reviewed the adult patients with FBs treated between 2001 and 2011 in China. The
      demographic and endoscopic data were collected and analyzed. RESULTS: A total of
      200 adult patients (136 men and 64 women) with an average age of 51 years were
      analyzed. The most common FBs included bones (51.0%), nut shells (15.0%), food
      boluses (7.0%), plastic toys or pen caps (6.5%). After FB aspiration occurred,
      only 11.0% were diagnosed within three days, while more than half of the patients
      (58.0%) delayed the diagnosis by more than one month. The incidence of FB-related
      complications was 79.5%, including granulation formation (76.5%), obstructive
      pneumonia (22.0%), hemorrhage (14.5%), atelectasis (10.0%) and endobronchial
      stenotic scarring (8.0%). In 96.5% of the patients, the FBs were successfully
      removed under flexible bronchoscopy. A total of 53 out of the 153 patients with
      granulation (34.6%) were managed by argon plasma coagulation (APC) or
      cryotherapy; two out of the sixteen patients with endobronchial stenotic scars
      were treated by balloon dilation under flexible bronchoscopy. CONCLUSION: A high
      incidence of FB-related complications occurs, likely as a result of the long
      delay between aspiration and diagnosis, a proportion of which require endoscopic
      intervention. The removal of FBs under flexible bronchoscopy has a high success
      rate and therefore should be recommended for adults.

PMID- 22989821
TI  - Weight of the CURB-65 criteria for community-acquired pneumonia in a very low
      mortality-rate setting.
AB  - OBJECTIVE: The CURB-65 score is a simple well validated tool for the assessment
      of severity in community-acquired pneumonia (CAP). The weight of each criterion
      in very low-mortality-rate settings is unclear. The purpose of this study was to
      determine the weight in such setting. METHODS: This study retrospectively
      reviewed 1,230 adult patients admitted for CAP from 2005 to 2009. RESULTS: The 30
      day mortality rose sharply from 0%, 1.0%, 8.2% and 16.7%, respectively, for
      patients with CURB-65 scores of 0, 1, 2 and 3 to 100.0% for patients with the
      scores of 4 (x(2) = 219.494, p<0.001). Confusion had the strongest association
      with mortality (odds ratio, 22.148). The presence of low blood pressure was not
      associated with mortality. Confusion, urea >7 mmol.L(-1) and age >= 65 yrs showed
      independent relationships with mortality (Odds ratio, 11.537, 5.988 and 10.462;
      respectively). Urea >7 mmol.L(-1) was most strongly associated with the
      sequential organ failure assessment (SOFA) scores [rank correlation coefficient
      (r(s)), 0.352]. Confusion had the closest relationship with hospital length of
      stay (r(s), 0.114). Age >= 65 yrs had the strongest association with costs (r(s),
      0.223). Conclusion The individual CURB-65 criteria were of unequal weight for
      predicting the 30-day mortality, SOFA scores, hospital length of stay and costs
      in a very low-mortality-rate setting, and a low blood pressure was not associated
      with mortality.

PMID- 22989822
TI  - Clinical features of 66 lymphoma patients presenting with a fever of unknown
      origin.
AB  - OBJECTIVE: To investigate the clinical characteristics, diagnostic approaches,
      short-term efficacy of treatment and prognosis of lymphoma patients presenting
      with a fever of unknown origin (FUO). METHODS: We reviewed the records of 132
      patients finally diagnosed with lymphoma in Huashan Hospital, half of whom
      initially presented with a FUO. The other 66 lymphoma patients without a history
      of FUO were diagnosed within a month when several patients in the FUO group were
      also diagnosed. RESULTS: The patients presenting with a FUO were predominantly
      young men (71.21%, p=0.35) characterized by a temperature >= 39 degrees C (55/66,
      83.33%). Compared with the non-FUO group, patients in the FUO group more often
      had pancytopenia and hypohepatia, 61.54% with hypoalbuminemia (p<0.0001), 15.50%
      with significantly elevated lactate dehydrogenase (LDH) (p<0.0001), 92.45% with
      elevated serum beta(2) microglobulin (p=0.017), 93.48% with elevated urine
      beta(2) microglobulin (p=0.002) and 30.77% with elevated alkaline phosphatase
      (p=0.001). Ninety-four percent of the FUO patients had aggressive lymphomas
      (p=0.012), with a poor performance status (96.97%, p=0.003), stage III/IV disease
      (96.97%, p<0.0001), night sweats (21.21%, p=0.026), unexplained weight loss
      (46.97%, p=0.002) and more than one extranodal site involved (65.15%, p=0.002).
      The patients in the FUO group also showed poor prognoses, and most of them were
      in the high-intermediate or high risk classification of the disease (96.61%,
      p<0.0001), with a low complete remission (CR) rate (61.11% vs. 93.75%, p=0.043).
      Twenty-one (15.91%) of all the patients were diagnosed based on the finding of
      lesion sites by Positron Emission Tomography/Computed Tomography (PET/CT)
      scanning, which had not been detected by conventional scans. CONCLUSION: Lymphoma
      presenting as FUO has a rapid progression and poor prognosis, and is difficult to
      diagnose. PET/CT scans can provide complementary information for an etiological
      diagnosis of a FUO and biopsy examinations are significant to establish an early
      diagnosis for patients presenting with a FUO.

PMID- 22989823
TI  - Clinical characteristics of nursing and healthcare-associated pneumonia: a
      Japanese variant of healthcare-associated pneumonia.
AB  - OBJECTIVE: The aim of this study was to describe the epidemiology, clinical
      features, antimicrobial treatment, and outcomes of patients with nursing and
      healthcare-associated pneumonia (NHCAP); a new category of pneumonia proposed by
      the Japanese Respiratory Society. METHODS: We conducted a retrospective analysis
      of a prospectively collected database of patients with NHCAP and community
      acquired pneumonia (CAP) hospitalized at a single center between January 2008 and
      December 2010, and compared their clinical characteristics. The criteria for
      NHCAP were as follows: (1) residence in a nursing home or an extended-care ward,
      (2) a discharge from a hospital in the preceding 90 days, (3) an elderly or
      handicapped patient who needs long-term care, (4) a patient who regularly
      requires vascular access in an outpatient setting. RESULTS: A total of 442 NHCAP
      patients and 451 CAP patients were evaluated. The NHCAP patients were older and
      had a higher frequency of underlying diseases. Aspiration was thought to be
      associated with the NHCAP in 63% of patients. Streptococcus pneumoniae was the
      leading pathogen in both groups, whereas the frequency of multidrug-resistant
      pathogens was higher in the NHCAP patients. The most frequently used
      antimicrobials in NHCAP patients were penicillins with beta-lactamase inhibitors.
      The in-hospital mortality and recurrence rates were significantly higher in NHCAP
      patients than in CAP patients (13.1% vs. 5.1%, p<0.001 and 18.8% vs. 5.5%,
      p<0.001). CONCLUSION: The clinical picture of NHCAP is consistent with that of
      HCAP described in the past. It is thought to be of benefit to modify the
      healthcare-associated pneumonia (HCAP) criteria considering the healthcare and
      social health insurance system in Japan.

PMID- 22989824
TI  - Adult intussusception caused by Yersinia enterocolitica enterocolitis.
AB  - Yersinia enterocolitica (YE) infection is a rare cause of intestinal
      intussusception, especially in adults. We herein, report a case of adult
      intussusception due to YE enterocolitis. A 24-year-old woman was admitted because
      of severe abdominal pain. She was clinically diagnosed with ileocolic
      intussusception on the basis of the findings of computed tomography (CT) and a
      gastrografin enema. Manual surgical reduction was sufficient to alleviate the
      intussusception. A histological examination of the lymph nodes around the
      ileocecum excluded lymphoma. Serological testing revealed that the cause of the
      intussusception was a YE infection. The patient's postoperative course was good
      and no recurrence was seen during the follow-up.

PMID- 22989825
TI  - Eosinophilic enteritis: efficiency of the 13C-acetate breath test for assessing
      the disease activity.
AB  - Few clinical studies have so far focused on gastrointestinal motility in patients
      with eosinophilic gastroenteritis. A 29-year-old man was evaluated for
      epigastralgia of unknown origin. A histopathological examination of biopsy
      specimens from the duodenum revealed numerous eosinophilic infiltrations.
      Eosinophilic enteritis was therefore diagnosed. The patient received oral
      prednisolone and his symptoms improved. Both at the onset and at relapse of the
      disease, the maximal (13)CO(2) excretion time (T(max)) of (13)C-acetate breath
      test was noted to have increased levels of excretion. Recovery of this parameter
      was observed in parallel with clinical improvements after treatments. This is the
      first report of a case of eosinophilic enteritis in which the (13)C-acetate
      breath test was effective for assessing the disease activity and evaluating the
      effectiveness of treatment.

PMID- 22989826
TI  - Gastrointestinal stromal tumors of the stomach with extensive calcification:
      report of two cases.
AB  - Gastrointestinal stromal tumors (GISTs) can present with focal calcification.
      However, the presence of extensive calcification that constitutes the major
      portion of a GIST is extremely rare and can be associated with diagnostic
      pitfalls. We herein present the first two cases of rare gastric GIST with
      predominantly calcified components that mimicked pancreatic solid and
      pseudopapillary neoplasms with extensive calcification. In patients presenting
      with hyper-dense, heavily calcified masses in the abdominal cavity, the
      possibility of GIST should be considered in the differential diagnosis. A careful
      search for cellular areas and the judicious application of immunostaining will
      thus make it possible to make a correct diagnosis.

PMID- 22989827
TI  - Dilated phase of hypertrophic cardiomyopathy caused by two different sarcomere
      mutations, treated with surgical left ventricular reconstruction and cardiac
      resynchronization therapy with a defibrillator.
AB  - We herein report the case of a 61-year-old woman with dilated phase of
      hypertrophic cardiomyopathy (D-HCM) who had been diagnosed with HCM 17 years
      previously. On admission, her left ventricle (LV) had marked dilation,
      dyssynchrony with diffuse severe hypokinesis, and ventricular tachycardia. She
      had two mutations in the cardiac myosin binding protein-C gene, which were
      suspected to be the causes of the D-HCM. We performed LV reconstruction surgery
      and cardiac resynchronization therapy with a defibrillator for her drug-resistant
      severe heart failure. After surgery, her New York Heart Association class
      dramatically improved, and she has not been re-hospitalized since these
      treatments.

PMID- 22989828
TI  - Cardiogenic shock due to left ventricular outflow obstruction and complete
      atrioventricular block in a patient with hypertrophic cardiomyopathy with acute
      myocarditis.
AB  - A 67-year-old woman was referred to our hospital with a sudden syncopal attack.
      She suffered from cardiogenic shock due to left ventricular (LV) outflow stenosis
      with simultaneous complete atrioventricular (AV) block. An endomyocardial biopsy
      of the left ventricle demonstrated myocardial disarray and myocardial fibrous and
      edematous tissue with infiltration of mononuclear cells. Cardiac magnetic
      resonance imaging (cMRI) detected a damaged septal area that was likely
      associated with the conduction disturbance. The diagnosis was hypertrophic
      cardiomyopathy accompanied by acute myocarditis. Although the LV outflow stenosis
      was transient, the complete AV block was persistent, thus requiring permanent
      pacemaker implantation.

PMID- 22989829
TI  - Premature atherosclerosis in a Japanese diabetic patient with atypical familial
      partial lipodystrophy and hypertriglyceridemia.
AB  - We herein report a case of premature atherosclerosis in a patient with familial
      partial lipodystrophy (FPL), diabetes mellitus, hypertension and
      hypertriglyceridemia. Sequencing of the candidate genes LMNA, PPARG and CAV1
      associated with FPL revealed no genetic abnormalities, which indicated the
      activity of a novel gene in this patient. The patient's son showed milder fat
      loss and similar fat distribution compared to the proband; however, the son
      showed no signs of any atherosclerotic disease. Although a cluster of atherogenic
      risk factors is likely to be the primary causes of atherosclerosis in our
      patient, other factors, including an unknown gene associated with FPL, the
      severity of fat loss and gender, might affect the development of atherosclerosis.

PMID- 22989830
TI  - Successful treatment of reactive hypoglycemia secondary to late dumping syndrome
      using miglitol.
AB  - We herein describe a 59-year-old woman who had undergone a total gastrectomy for
      gastric carcinoma and suffered from postprandial hypoglycemia characterized by a
      loss of consciousness and spasms. She was diagnosed with reactive hypoglycemia
      and treated with nutrition therapy, but the frequency and severity of the
      hypoglycemic episodes did not decrease. She was subsequently treated successfully
      with miglitol, an alpha-glucosidase inhibitor (alpha-GI) taken twice a day; other
      alpha-GIs (acarbose and voglibose) were not effective. In conclusion, the
      administration of miglitol was effective for preventing reactive hypoglycemia
      secondary to late dumping syndrome.

PMID- 22989831
TI  - Rapidly progressive glomerulonephritis associated with PR3-ANCA positive subacute
      bacterial endocarditis.
AB  - Patients with bacterial endocarditis often have renal complications. This report
      presents the case of an elderly man with rapidly progressive glomerulonephritis
      (RPGN) associated with subacute bacterial endocarditis (SBE) due to Enterococcus
      faecalis infection. The patient was positive for anti-proteinase 3-antineutrophil
      cytoplasmic antibody (PR3-ANCA) and rheumatoid factor (RF) with
      hypocomplementemia. Treatment for SBE with antibiotics and the surgical
      replacement of the affected valves resulted in an improvement of RPGN, the
      disappearance of PR3-ANCA and RF, and the normalization of hypocomplementemia.
      This rare case suggests the importance of recognizing the cause of positive PR3
      ANCA, because SBE could be an occult cause of RPGN mimicking ANCA-associated
      vasculitis.

PMID- 22989832
TI  - Distal renal tubular acidosis that became exacerbated by proton pump inhibitor
      use.
AB  - Acid-base imbalances and electrolyte disorders induced by proton pump inhibitors
      (PPIs) are extremely rare. However, under certain conditions, PPIs may cause
      metabolic acidosis or hypokalemia, probably due to an inhibitory action on the
      proton pump that contributes to H(+) and K(+) homeostasis in the kidney. We
      herein present a case of marked hypokalemia accompanied by distal renal tubular
      acidosis in which a PPI appeared to contribute to the pathophysiology of
      metabolic acidosis.

PMID- 22989833
TI  - Low-density lipoprotein apheresis therapy for steroid- and cyclosporine-resistant
      idiopathic membranous nephropathy.
AB  - We herein report three cases of Nephrotic Syndrome (NS) with idiopathic
      membranous nephropathy (IMN) in which the patients were resistant to steroid
      (PSL) and cyclosporine (CyA) therapy. All three patients had a high risk of renal
      failure because of persistently high levels of proteinuria. We performed low
      density lipoprotein apheresis (LDL-A) and achieved complete remission in two
      cases. The third patients developed NS relapse and a deteriorating renal
      function; however, withdrawal from dialysis therapy was achieved. There are no
      proven therapies for treating patients with PSL- and CyA-resistant IMN with acute
      deteriorating renal function or difficulties in maintaining fluid balance. We
      evaluated the treatment course and physiological mechanisms and reviewed similar
      cases in the pertinent literature.

PMID- 22989834
TI  - Pulmonary tumor embolism secondary to uterine corpus carcinosarcoma mimicking
      pulmonary thromboembolism.
AB  - We herein report a case of pulmonary tumor embolism caused by hematogenous
      metastasis that mimicked pulmonary thromboembolism in a 62-year-old Japanese
      woman with a history of uterine corpus carcinosarcoma. The case suggests that
      tumor embolism must be included in the differential diagnoses of respiratory
      symptoms in patients with a history of malignancy. It also illustrates the
      usefulness of such findings as beaded, dilated pulmonary arteries by computed
      tomography (CT) and high (18)F-fluorodeoxyglucose (FDG) uptake by fusion FDG
      positron emission tomography/CT imaging for differentiating a pulmonary tumor
      embolism from pulmonary thromboembolism.

PMID- 22989835
TI  - Soft J-tipped guide wire-induced cardiac perforation in a patient with right
      ventricular lipomatosis and wall thinning.
AB  - Cardiac tamponade caused by perforation is a rare but potentially lethal
      complication of central venous catheter (CVC) insertion. We herein report a case
      of cardiac perforation associated with the use of a soft J-tipped guide wire.
      Twenty minutes after the insertion of a CVC, the patient developed unexpected
      cardiac arrest. An autopsy revealed 400 mL of pericardial blood. The right
      ventricular wall was 1 mm thick with about 10 myocyte layers, which is one-third
      that of the normal heart. A histological analysis revealed widespread fatty
      infiltration of the right ventricular wall (right ventricular lipomatosis).

PMID- 22989836
TI  - Successful management of obstructive jaundice due to gallstones with eculizumab
      in a patient with paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) makes patients susceptible to
      intravascular hemolysis and thrombosis, and it can be life-threatening in
      stressful situations. Eculizumab, a humanized monoclonal antibody that inhibits
      the complement protein C5, has been evaluated as a novel therapy for PNH. We
      herein describe the case of a 59-year-old Japanese woman with classic PNH, who
      had been successfully treated with eculizumab, but who later developed acute
      cholecystitis/cholangitis from gallstones. Although the severe obstructive
      jaundice requiring endoscopic therapy following cholecystectomy was complicated,
      critical intravascular hemolysis and thrombosis were not observed. Therefore,
      utilizing eculizumab during the peri-operative management of PNH patients should
      be carefully taken into consideration.

PMID- 22989837
TI  - HyperCKemia related to the initial and recurrent attacks of neuromyelitis optica.
AB  - We herein report the case of a 60-year-old man showing overexpression of creatine
      kinase (hyperCKemia) related to initial and recurrent attacks of neuromyelitis
      optica (NMO). He showed reduced vision, ataxia and dysesthesia, but no symptoms
      originating in the muscles. Magnetic resonance imaging (MRI) revealed lesions in
      the optic nerve, medulla oblongata, and spinal cord similar to typical NMO
      patients. However, femoral MRI and whole positron emission tomography (PET)
      demonstrated no abnormal findings during an episode of hyperCKemia. This case
      suggests that hyperCKemia is partly involved in the pathogenesis of NMO in both
      the central nervous system and myofiber surface, which is usually difficult to
      detect by clinical imaging modalities alone.

PMID- 22989838
TI  - Miller Fisher syndrome associated with influenza A infection.
AB  - A 36-year-old, previously healthy man presented with Miller Fisher syndrome (MFS)
      five days after he was diagnosed with an influenza A infection by a rapid antigen
      test. He had not received any recent vaccinations. He had no loss of
      consciousness. Bilateral ophthalmoplegia, blepharoptosis, areflexia, and ataxic
      gait were noted. One week after treatment with intravenous immunoglobulin, his
      ophthalmoplegia, blepharoptosis, and ataxic gait had gradually improved, and his
      deep tendon reflexes returned. Anti-GQ1b IgG antibodies were detected in his
      serum. There has been no previous report of postinfectious MFS following
      confirmed an influenza A infection in an adult.

PMID- 22989839
TI  - New-onset type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic
      neuritis associated with type 1 interferon therapy for chronic hepatitis C.
AB  - A 60-year-old woman developed type 1 diabetes mellitus and anti-aquaporin-4
      antibody positive optic neuritis during type 1 interferon therapies for chronic
      hepatitis C. The diabetes mellitus was elicited by interferon-alpha plus
      ribavirin therapy, while the optic neuritis was induced after interferon-beta
      treatment, followed by interferon-alpha and ribavirin therapy. It is possible
      that type 1 interferons lead to the onset of the two autoimmune diseases by
      inducing disease-specific autoantibodies. Autoimmune disease is an infrequent
      complication of type 1 interferon treatment; however, once it has occurred, it
      may result in severe impairments. Patients undergoing type 1 interferon therapy
      should therefore be carefully monitored for any manifestations of autoimmune
      diseases.

PMID- 22989840
TI  - Syncope induced by acute pulmonary embolism in aged patients: a report of four
      cases.
AB  - Syncope is a common presentation in the neurology clinic and emergency room.
      However, pulmonary embolism (PE) as a cause of syncope is not common or well
      recognized. Four aged patients presented to our clinic with episodic syncope, and
      PE was finally identified as the underlying cause. The significant clinical
      presentations included transient loss of consciousness and hypoxemia on
      admission. Syncope with hypoxia should therefore be highlighted as an important
      clue to the diagnosis of PE in aged patients. A negative D-dimer test will be
      encountered in patients with a very short history. Repeated D-dimer testing is
      necessary.

PMID- 22989841
TI  - Severe main coronary artery disease in a young woman with ankylosing spondylitis.
AB  - Patients with ankylosing spondylitis (AS) have an approximately two-fold
      increased death rate compared to the general population, which is predominately
      caused by increased cardiovascular risk. The prevalence rate for myocardial
      infarction is approximately 2-3 fold increased as compared with the general
      population. The inflammatory process appears to have an important role in causing
      this excess cardiovascular risk. In this paper, we present a case of severe
      coronary artery disease which could be demonstrated clearly by computer
      tomography in a 27-year-old woman who is being followed with AS.

PMID- 22989842
TI  - Co-infection with group A Streptococci and Epstein-Barr virus presenting with
      acute glomerulonephritis and acute left ventricular dysfunction.
AB  - Acute pharyngitis is commonly encountered, but a definite etiological diagnosis
      is difficult. Although co-infection with Group A Streptococci (GAS) and Epstein
      Barr virus (EBV) is uncommon, general physicians should consider the possibility
      of EBV co-infection in patients with GAS pharyngitis who fail to show prompt
      remission of symptoms following appropriate antibiotic treatment. In this
      article, we present a rare case of a 16-year-old girl who had co-infection with
      GAS and EBV. She developed acute glomerulonephritis and left ventricular
      dysfunction in an overlapping manner. We were able to follow her until she
      healed, and herein describe the pathogenesis of her systemic and pulmonary edema.

PMID- 22989843
TI  - Postoperative meningitis and epidural abscess due to extended-spectrum beta
      lactamase-producing Klebsiella pneumoniae: a case report and a review of the
      literature.
AB  - 17-year-old man had been involved in a traffic accident. He underwent a bilateral
      craniotomy with artificial dura mater to remove bilateral acute subdural
      hematomas. Seven months later, a right cranioplasty was performed using frozen
      auto-bone, and he developed extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae meningitis and an epidural abscess. Since his general
      status was poor, we could not remove the foreign body (artificial dura mater). He
      was successfully treated with meropenem and chronic suppression with oral
      trimethoprim-sulfamethoxazole. By describing this case and the results of a
      review of the pertinent literature, we discuss the importance of ESBL-producing
      Klebsiella pneumoniae meningitis in posttraumatic/postoperative patients.

PMID- 22989845
TI  - Bilateral pleural fluid caused by a pancreaticopleural fistula requiring surgical
      treatment.
AB  - A 53-year-old man developed bilateral pleural effusion with respiratory failure.
      The amylase level in the pleural effusion was elevated. He had neither abdominal
      symptoms nor abdominal physical findings. Abdominal computed tomography (CT) also
      showed no abnormalities. Magnetic resonance cholangiopancreatography (MRCP) was
      non-diagnostic, but endoscopic retrograde cholangiopancreatography (ERCP) and
      subsequent CT showed a fistula connecting the pancreatic duct with the right
      pleural cavity. The pleural effusion was refractory to drug therapy, leading to
      the need for surgical intervention. The pathological findings revealed chronic
      pancreatitis without pseudocysts. The elevated pancreatic amylase in the pleural
      effusion offered an important clue to the correct diagnosis.

PMID- 22989844
TI  - Familial Mediterranean fever with onset at 66 years of age.
AB  - The patient was a 68-year-old woman who had experienced recurrent febrile
      episodes since 66 years of age. Despite various examinations and treatments, the
      etiology remained unclear. Further examinations following another referral failed
      to uncover the cause. Therefore, despite her age, it was presumed that she had
      familial Mediterranean fever. An analysis of the familial Mediterranean fever
      (MEFV) gene detected heterozygous L110P, E148Q, and R202Q mutations. No further
      febrile episodes occurred after colchicine treatment was initiated. Familial
      Mediterranean fever presenting in patients in their sixties is extremely rare.

PMID- 22989846
TI  - Battery ingestion: the importance of careful radiographic assessment.

PMID- 22989847
TI  - Hepatic portal venous gas.

PMID- 22989848
TI  - Diffuse alveolar hemorrhage associated with dabigatran.

PMID- 22989849
TI  - Complete occlusion of the left main coronary artery trunk.

PMID- 22989850
TI  - Emphysematous pyelonephritis mimicking hollow organ perforation.

PMID- 22989851
TI  - Acute hemorrhage in a giant bulla.

PMID- 22989852
TI  - Small dense LDL: An emerging risk factor for cardiovascular disease.
AB  - Although low-density lipoprotein cholesterol (LDL-C) is a strong risk factor for
      coronary artery disease (CAD), LDL-C levels are not always elevated in CAD
      patients. LDL consists of several subclasses with distinct sizes, densities, and
      physicochemical compositions. Thus, LDL subclasses can be separated by various
      laboratory procedures. Among them, ultracentrifugation and electrophoresis have
      been used most frequently for determining LDL subclasses. Accumulating evidence
      has shown that a predominance of small dense LDL (sd-LDL) is closely associated
      with CAD. Moreover, sd-LDL-cholesterol (sd-LDL-C) concentrations are elevated in
      groups at a high risk for CAD, such as patients with type 2 diabetes and
      metabolic syndrome. Therefore, sd-LDL concentration is recognized as a surrogate
      marker for CAD. However, some studies failed to show therapeutic modulation of sd
      LDL, likely because separating methods and sd-LDL particle definitions have not
      yet been standardized. Recently, a detergent-based homogenous assay for sd-LDL-C
      has been developed. This method does not require any pretreatment, and the
      measured values are highly reproducible with an automated analyzer. These
      features are suitable for large-scale clinical studies. This homogeneous assay is
      a useful tool for clarifying whether sd-LDL-C is a superior marker to LDL-C, and
      whether sd-LDL-C lipid-lowering therapies decrease the incidence of CAD.

PMID- 22989853
TI  - The involvement of limbic structures in typical and atypical absence epilepsy.
AB  - Typical and atypical seizures of absence epilepsy are thought to be generated by
      a rhythmogenic interplay between the cortex and the thalamus. However, the
      question remains as to which other subcortical and extrathalamic structures are
      involved in the pathophysiology of typical and atypical absence epilepsy. Limbic
      structures are not thought to be involved in typical absence seizures, since in
      animal models and human patients there is no evidence for the occurrence of spike
      and-wave discharges of absence seizures in the limbic regions. However, there are
      a number of observations from animal models of absence epilepsy that point to a
      possibly important link between absence seizure mechanisms and limbic structures.
      Atypical absence seizures are distinct in many ways from typical absence seizures
      although they bear considerable clinical, EEG, and pharmacological resemblance to
      typical absence seizures. The differences between typical and atypical seizures
      of absence epilepsy appear to be circuitry dependent. While both typical and
      atypical absence seizures involve the cortico-thalamo-cortical circuitry, they
      each engage different neuronal networks within that circuitry. This review
      examines the involvement of limbic structures in typical and atypical absence
      seizures, shows that limbic circuitry forms an integral component of the absence
      epilepsy network and concludes that further knowledge of this component is
      important for understanding the complex relationships involved in absence
      epilepsy.

PMID- 22989854
TI  - Age-accelerated psychomotor slowing in temporal lobe epilepsy.
AB  - Cognitive and psychomotor slowing is a complication of epilepsy and is less often
      a focus of investigation relative to other cognitive domains (e.g., memory). A
      diversity of tasks has been used to examine psychomotor slowing in epilepsy, but
      it remains unknown whether the degree of epilepsy-related slowing is fixed or is
      exacerbated with increasing task demand. Also unknown is to what degree age
      related slowing is accelerated in epilepsy. Participants with temporal lobe
      epilepsy (n=50) were compared to healthy controls (n=69) across three tasks of
      psychomotor speed with varied complexity. Performance was examined as a function
      of group (epilepsy, controls), task complexity (simple, intermediate, complex),
      and chronological age. The results showed that speed of performance declined
      across the epilepsy and control participants as a function of task complexity.
      Epilepsy participants were significantly slower than controls across the three
      tasks, and there was a significant three-way interaction (group by task
      complexity by age). These results demonstrate that psychomotor slowing is related
      to task complexity in both epilepsy and healthy control participants, always
      greater in epilepsy participants, and there is a significant age acceleration of
      psychomotor slowing in the epilepsy group that is magnified by complex tasks.

PMID- 22989855
TI  - Impact of teaching intensity and academic status on medical resource utilization
      by teaching hospitals in Japan.
AB  - Teaching hospitals require excess medical resources to maintain high-quality care
      and medical education. To evaluate the appropriateness of such surplus costs, we
      examined the impact of teaching intensity defined as activities for postgraduate
      training, and academic status as functions of medical research and undergraduate
      teaching on medical resource utilization. Administrative data for 47,397
      discharges from 40 academic and 12 non-academic teaching hospitals in Japan were
      collected. Hospitals were classified into three groups according to
      intern/resident-to-bed (IRB) ratio. Resource utilization of medical services was
      estimated using fee-for-service charge schedules and normalized with case mix
      grouping. 15-24% more resource utilization for laboratory examinations,
      radiological imaging, and medications were observed in hospitals with higher IRB
      ratios. With multivariate adjustment for case mix and academic status, higher IRB
      ratios were associated with 10-15% more use of radiological imaging, injections,
      and medications; up to 5% shorter hospital stays; and not with total resource
      utilization. Conversely, academic status was associated with 21-33% more
      laboratory examinations, radiological imaging, and medications; 13% longer
      hospital stays; and 10% more total resource utilization. While differences in
      medical resource utilization by teaching intensity may not be associated with
      indirect educational costs, those by academic status may be. Therefore, academic
      hospitals may need efficiency improvement and financial compensation.

PMID- 22989856
TI  - Evaluating and improving orphan drug regulations in Europe: a Delphi policy
      study.
AB  - To encourage the development of orphan drugs, the European Union has implemented
      specific policies in 2000. However, the political, social, scientific and
      economic context has changed since the implementation of these policies. For that
      reason, the aim of this article is to evaluate orphan drug policies in Europe.
      Firstly, key issues on the orphan drug policy were identified based on desk
      research. Secondly, a Delphi policy study with 47 European orphan drug experts
      from different backgrounds was carried out to explore these issues. In the round
      one of the Delphi, responses were received from 18 experts (38.3%) and from ten
      (55.5%) in the round two. Experts agree that the orphan drug policies in Europe
      have not outlived their usefulness. Additionally, the importance of reducing
      country-dependent inequalities in patient access to orphan drugs has been
      emphasized. Still, there is room for further refinement of the orphan drug
      policies. Within that context, we formulated several policy recommendations (e.g.
      enforcing the policy that is in place to reduce the period of market exclusivity
      for profitable orphan drugs, stating the level of clinical evidence needed to
      authorize orphan drugs, etc.) with the overall goal to optimize patient access to
      orphan drugs.

PMID- 22989857
TI  - Physiological responses of Tillandsia albida (Bromeliaceae) to long-term foliar
      metal application.
AB  - The impact of 2-month foliar application of cadmium, nickel and their combination
      (10 MUM) on Tillandsia albida was studied. Cadmium caused damage of tissue but
      assimilation pigments were depressed in Cd+Ni variant only. Stress-related
      parameters (ROS and peroxidase activities) were elevated by Cd and Cd+Ni while
      MDA content remained unaffected. Free amino acids accumulated the most in Ni
      alone but soluble proteins were not influenced. Among phenolic acids, mainly
      vanillin contributed to increase of their sum in all variants while soluble
      phenols even decreased in Cd+Ni and flavonols slightly increased in Cd variants.
      Phenolic enzymes showed negligible responses to almost all treatments. Mineral
      nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by metal application but
      N content increased. Total Cd or Ni amounts reached over 400 MUg g(-1) DW and
      were not affected if metal alone and combined treatment is compared while
      absorbed content differed (ca. 50% of total Cd was absorbed while almost all Ni
      was absorbed). These data indicate tolerance of T. albida to foliar metal
      application and together with strong xerophytic morphology, use for environmental
      studies is recommended.

PMID- 22989858
TI  - Intrinsically disordered proteins: a 10-year recap.
AB  - The suggestion that the native state of many proteins is intrinsically disordered
      (or, as originally termed, unstructured) is now integral to our general view of
      protein structure and function. A little more than 10 years ago, however, such
      challenge to the almost dogmatic 'structure-function paradigm' was pure heresy
      due to the overwhelming evidence that structure determines function. A decade of
      steady progress turned skepticism around: this 10-year recap review outlines the
      situation a decade ago and the major directions of the breathtaking advance
      achieved by experimental and computational approaches. I show that the evidence
      for the generality and importance of this phenomenon is now so insurmountable
      that it demands the inclusion of 'unstructural' biology into mainstream biology
      and biochemistry textbooks.

PMID- 22989860
TI  - Estradiol treatment in preadolescent females enhances adolescent spatial memory
      and differentially modulates hippocampal region-specific phosphorylated ERK
      labeling.
AB  - Estrogen levels in rats are positively correlated with enhanced memory function
      and hippocampal dendritic spine density. There is much less work on the long-term
      effects of estradiol manipulation in preadolescent rats. The present work
      examined how injections of estradiol during postnatal days 19-22 (p19-22;
      preadolescence) affected water maze performance and hippocampal phosphorylated
      ERK labeling. To investigate this, half of the estradiol- and vehicle-treated
      female rats were trained on a water maze task 24h after the end of estradiol
      treatment (p23-27) while the other half was not trained. All female rats were
      tested on the water maze from p40 to p44 (adolescence) and hippocampal pERK1/2
      labeling was assessed as a putative marker of neuronal plasticity. During
      adolescence, preadolescent-trained groups showed lower latencies than groups
      without preadolescent training. Retention data revealed lower latencies in both
      estradiol groups, whether preadolescent trained or not. Immunohistochemical
      detection of hippocampal pERK1/2 revealed elevations in granule cell labeling
      associated with the preadolescent trained groups and reductions in CA1 labeling
      associated with estradiol treatment. These results show a latent beneficial
      effect of preadolescent estradiol treatment on adolescent spatial performance and
      suggest an organizational effect of prepubescent exogenously applied estradiol.

PMID- 22989859
TI  - Differential calcium dependence in basal and forskolin-potentiated spontaneous
      transmitter release in basolateral amygdala neurons.
AB  - Action potential-independent transmitter release, or spontaneous release, is
      postulated to produce multiple postsynaptic effects (e.g., maintenance of
      dendritic spines and suppression of local dendritic protein synthesis).
      Potentiation of spontaneous release may contribute to the precise modulation of
      synaptic function. However, the expression mechanism underlying potentiated
      spontaneous release remains unclear. In this study, we investigated the
      involvement of extracellular and intracellular calcium in basal and potentiated
      spontaneous release. Miniature excitatory postsynaptic currents (mEPSCs) of the
      basolateral amygdala neurons in acute brain slices were recorded. Forskolin, an
      adenylate cyclase activator, increased mEPSC frequency, and the increase lasted
      at least 25 min after washout. Removal of the extracellular calcium decreased
      mEPSC frequency in both naive and forskolin-treated slices. On the other hand,
      chelation of intracellular calcium by BAPTA-AM decreased mEPSC frequency in
      naive, but not in forskolin-treated slices. A blockade of the calcium-sensing
      receptor (CaSR) resulted in an increase in mEPSC frequency in forskolin-treated,
      but not in naive slices. These findings indicate that forskolin-induced
      potentiation is accompanied by changes in the mechanisms underlying Ca(2+)
      dependent spontaneous release.

PMID- 22989861
TI  - Idiopathic eosinophilic cholecystitis: a cause of hydrops of gallbladder in a
      young adolescent.

PMID- 22989862
TI  - Unusual cause of biliary obstruction revealed by endoscopic ultrasound and
      peroral cholangioscopy.

PMID- 22989863
TI  - The bridges of chronic inflammatory bowel disease.

PMID- 22989864
TI  - Risk of esophagitis among individuals born preterm or small for gestational age.
AB  - BACKGROUND & AIMS: The association between gastroesophageal reflux and esophageal
      adenocarcinoma is likely to be mediated by inflammation. Reflux is common in
      infancy; the esophageal mucosa of infants born preterm or small for gestational
      age (SGA) could be particularly vulnerable. We investigated the association
      between preterm or SGA birth and risk of esophagitis early in life. METHODS: We
      analyzed data from the Swedish birth register and the Swedish patient register to
      identify birth characteristics of individuals with endoscopically verified
      esophagitis from 1973 to 2007 and to determine their outcomes (7358 cases). Five
      controls were selected randomly and matched with each case (N = 38,479).
      Multivariable conditional logistic regression models were used to provide odds
      ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential
      confounding. RESULTS: The risk of esophagitis was increased among individuals
      born preterm (<=32 gestational weeks) (OR, 2.74; 95% CI, 2.15-3.49) or SGA (OR,
      1.49; 95% CI, 1.32-1.68). When data were stratified by age at diagnosis and by
      sex, different risk patterns appeared. Among individuals diagnosed with
      esophagitis 9 years of age and younger, the OR for prematurity was 6.82 (95% CI,
      4.65-10.03) and the OR for SGA at birth was 1.98 (95% CI, 1.55-2.52).
      Furthermore, the association with preterm birth was stronger among males (OR,
      9.88; 95%, CI 5.93-16.45) than females (OR, 3.41; 95% CI, 1.81-6.41), whereas the
      association with SGA was stronger among females (OR, 2.50; 95% CI, 1.76-3.55)
      than males (OR, 1.64; 95% CI, 1.16-2.30). The risk of being diagnosed with
      esophagitis at age 20 or younger was not associated with preterm birth (OR, 1.02;
      95% CI, 0.64-1.63), but was associated with being SGA at birth (OR, 1.31; 95% CI,
      1.11-1.54). CONCLUSIONS: Preterm birth is associated with esophagitis only during
      childhood, whereas SGA birth is associated with esophagitis during adolescence as
      well. The associations appear to differ between sexes.

PMID- 22989865
TI  - Novel antagonists of heparin binding growth factors.
AB  - Structural and functional studies of ligand-RTK interactions over the last decade
      highlight the importance of multiple binding events and associated conformational
      changes in RTK ectodomains that are required for kinase activation. These events
      vary in strength, and even weak interactions appear to provide necessary
      increments of increased stability to a signal transduction process whose
      complexity we are only beginning to appreciate.

PMID- 22989866
TI  - Spin polarized and density modulated phases in symmetric electron-electron and
      electron-hole bilayers.
AB  - We have studied symmetric electron-electron and electron-hole bilayers to explore
      the stable homogeneous spin phase and the feasibility of inhomogeneous charge
      /spin-density ground states. The former is resolved by comparing the ground-state
      energies in states of different spin polarizations, while the latter is resolved
      by searching for a divergence in the wavevector-dependent static charge/spin
      susceptibility. For this endeavour, we have used the dielectric approach within
      the self-consistent mean-field theory of Singwi et al. We find that the inter
      layer interactions tend to change an abrupt spin-polarization transition of an
      isolated layer into a nearly gradual one, even though the partially spin
      polarized phases are not clearly stable within the accuracy of our calculation.
      The transition density is seen to decrease with a reduction in layer spacing,
      implying a suppression of spin polarization by inter-layer interactions. Indeed,
      the suppression shows up distinctly in the spin susceptibility computed from the
      spin-polarization dependence of the ground-state energy. However, below a
      critical layer spacing, the unpolarized liquid becomes unstable against a charge
      density-wave (CDW) ground state at a density preceding full spin polarization,
      with the transition density for the CDW state increasing on further reduction in
      the layer spacing. Due to attractive e-h correlations, the CDW state is found to
      be more pronounced in the e-h bilayer. On the other hand, the static spin
      susceptibility diverges only in the long-wavelength limit, which simply
      represents a transition to the homogeneous spin-polarized phase.

PMID- 22989869
TI  - Quality of life and survival in patients with heart failure.
AB  - AIMS: To examine whether self-rated disease-specific and generic quality of life
      predicts long-term mortality, independent of brain natriuretic peptide (BNP)
      levels, and to explore factors related to low quality of life in a well-defined
      heart failure (HF) population. METHODS AND RESULTS: A cohort of 661 patients (62%
      male; age 71 years; left ventricular ejection fraction 34%) was followed
      prospectively for 3 years. Quality of life questionnaires (Ladder of Life,
      RAND36, and Minnesota Living with Heart Failure Questionnaire) and BNP levels
      were assessed at discharge after a hospital admission for HF. Three-year
      mortality was 42%. After adjustment for demographic variables, clinical
      variables, and BNP levels, poor quality of life scores predicted higher
      mortality; per 10 units on the physical functioning [hazard ratio (HR) 1.08, 95%
      confidence interval (CI) 1.02-1.14] and general health (HR 1.08, 95% CI 1.01
      1.16) dimensions of the RAND36. Patients with low scores on these dimensions were
      more likely to be in New York Heart Association class III-IV, diagnosed with co
      morbidities, have suffered longer from HF, have lower estimated glomerular
      filtration rates, and have fewer beta-blocker prescriptions. CONCLUSION: Quality
      of life was independently related to survival in a cohort of hospitalized
      patients with HF. TRIAL REGISTRATION: NCT 98675639.

PMID- 22989867
TI  - Dynamics of bone turnover markers in patients with heart failure and following
      haemodynamic improvement through ventricular assist device implantation.
AB  - AIMS: Abnormal bone metabolism and progressive demineralization have been
      described in patients with heart failure (HF). We hypothesized that mechanical
      unloading through implantation of a ventricular assist device (VAD) with
      subsequent haemodynamic improvement would correct abnormal bone metabolism in
      patients with advanced HF. METHODS AND RESULTS: Serum was collected from 14
      controls, 20 patients with moderate HF, 34 patients with advanced HF undergoing
      VAD implantation, and 34 patients at the time of VAD explantation (mean duration:
      169 +/- 125 days). Bone metabolism markers were measured using enzyme-linked
      immunosorption assay (ELISA) or chemiluminescence immunoassay (CLIA). Compared
      with controls, HF patients showed increased parathyroid hormone (PTH: 42 +/- 19
      vs. 117 +/- 117 pg/mL in HF; P < 0.02) with decreased 25-hydroxyvitamin D
      [25(OH)D: 29 +/- 14 vs. 21 +/- 11 ng/mL in HF; P = 0.05]. While procollagen-1 N
      terminal peptide (P1NP) and osteocalcin were similar, cross-linked C- and N
      telopeptides of type I collagen (CTX and NTX) were both higher in HF (NTX: 14 +/-
      6 vs. 20 +/- 11 ng/mL; P < 0.05; CTX: 0.35 +/- 0.13 vs. 1.05 +/- 0.78 ng/mL; P <
      0.01 for controls and HF, respectively). P1NP increased markedly after VAD
      implantation (49 +/- 37 vs. 121 +/- 62 ng/mL; P < 0.0001), with a mild decrease
      in CTX and NTX levels indicating a shift towards anabolic bone formation. Serum
      PTH correlated with estimated glomerular filtration rate (r = -0.245, P < 0.05).
      CONCLUSION: Patients with advanced HF are characterized by increased levels of
      biochemical markers of bone resorption potentially as a result of secondary
      hyperparathyroidism and uncoupling of bone remodelling. Haemodynamic improvement
      and mechanical unloading after VAD implantation lead to correction of bone
      metabolism and increased levels of anabolic bone formation markers.

PMID- 22989870
TI  - Morphological assessment of the luminal surface of olfactory epithelium in mice
      deficient in tissue plasminogen activator following bulbectomy.
AB  - OBJECTIVE: This study aimed to investigate the function of tissue plasminogen
      activator in the olfactory epithelium of mice following neural injury. METHOD:
      Transmission electron microscopy was used to study the changes in the morphology
      of the olfactory epithelium 1-7 days after surgical ablation of the olfactory
      bulb (bulbectomy). RESULTS: Prior to bulbectomy, a uniformly fine material was
      observed within some regions of the olfactory epithelium of mice deficient in
      tissue plasminogen activator. At 2-3 days after bulbectomy, there were
      degenerative changes in the olfactory epithelium. At 5-7 days after bulbectomy,
      we noted drastic differences in olfactory epithelium morphology between mice
      deficient in tissue plasminogen activator and wild-type mice (comparisons were
      made using findings from a previous study). The microvilli seemed to be normal
      and olfactory vesicles and receptor neuron dendrites were largely intact in the
      olfactory epithelium of mice deficient in tissue plasminogen activator.
      CONCLUSION: The tissue plasminogen activator plasmin system may inhibit the
      regeneration of the olfactory epithelium in the early stages following neural
      injury.

PMID- 22989871
TI  - The function of consciousness in multisensory integration.
AB  - The function of consciousness was explored in two contexts of audio-visual
      speech, cross-modal visual attention guidance and McGurk cross-modal integration.
      Experiments 1, 2, and 3 utilized a novel cueing paradigm in which two different
      flash suppressed lip-streams cooccured with speech sounds matching one of these
      streams. A visual target was then presented at either the audio-visually
      congruent or incongruent location. Target recognition differed for the congruent
      versus incongruent trials, and the nature of this difference depended on the
      probabilities of a target appearing at these respective locations. Thus, even
      though the lip-streams were never consciously perceived, they were nevertheless
      meaningfully integrated with the consciously perceived sounds, and participants
      learned to guide their attention according to statistical regularities between
      targets and these unconsciously perceived cross-modal cues. In Experiment 4,
      McGurk stimuli were presented in which the lip-streams were either flash
      suppressed (4a) or unsuppressed (4b), and the McGurk effect was found to vanish
      under conditions of flash suppression. Overall, these results suggest a simple
      yet fundamental principle regarding the function of consciousness in multisensory
      integration - cross-modal effects can occur in the absence of consciousness, but
      the influencing modality must be consciously perceived for its information to
      cross modalities.

PMID- 22989872
TI  - Predictable locations aid early object name learning.
AB  - Expectancy-based localized attention has been shown to promote the formation and
      retrieval of multisensory memories in adults. Three experiments show that these
      processes also characterize attention and learning in 16- to 18-month old infants
      and, moreover, that these processes may play a critical role in supporting early
      object name learning. The three experiments show that infants learn names for
      objects when those objects have predictable rather than varied locations, that
      infants who anticipate the location of named objects better learn those object
      names, and that infants integrate experiences that are separated in time but
      share a common location. Taken together, these results suggest that localized
      attention, cued attention, and spatial indexing are an inter-related set of
      processes in young children that aid in the early building of coherent object
      representations. The relevance of the experimental results and spatial attention
      for everyday word learning are discussed.

PMID- 22989873
TI  - Solution NMR structure of the Ca2+-bound N-terminal domain of CaBP7: a regulator
      of golgi trafficking.
AB  - Calcium-binding protein 7 (CaBP7) is a member of the calmodulin (CaM) superfamily
      that harbors two high affinity EF-hand motifs and a C-terminal transmembrane
      domain. CaBP7 has been previously shown to interact with and modulate
      phosphatidylinositol 4-kinase III-beta (PI4KIIIbeta) activity in in vitro assays
      and affects vesicle transport in neurons when overexpressed. Here we show that
      the N-terminal domain (NTD) of CaBP7 is sufficient to mediate the interaction of
      CaBP7 with PI4KIIIbeta. CaBP7 NTD encompasses the two high affinity Ca(2+)
      binding sites, and structural characterization through multiangle light
      scattering, circular dichroism, and NMR reveals unique properties for this
      domain. CaBP7 NTD binds specifically to Ca(2+) but not Mg(2+) and undergoes
      significant conformational changes in both secondary and tertiary structure upon
      Ca(2+) binding. The Ca(2+)-bound form of CaBP7 NTD is monomeric and exhibits an
      open conformation similar to that of CaM. Ca(2+)-bound CaBP7 NTD has a solvent
      exposed hydrophobic surface that is more expansive than observed in CaM or CaBP1.
      Within this hydrophobic pocket, there is a significant reduction in the number of
      methionine residues that are conserved in CaM and CaBP1 and shown to be important
      for target recognition. In CaBP7 NTD, these residues are replaced with isoleucine
      and leucine residues with branched side chains that are intrinsically more rigid
      than the flexible methionine side chain. We propose that these differences in
      surface hydrophobicity, charge, and methionine content may be important in
      determining highly specific interactions of CaBP7 with target proteins, such as
      PI4KIIIbeta.

PMID- 22989874
TI  - CD3-T cell receptor co-stimulation through SLAMF3 and SLAMF6 receptors enhances
      RORgammat recruitment to the IL17A promoter in human T lymphocytes.
AB  - Th17 lymphocytes play a key role during immune responses against bacteria and
      fungi and are involved in the pathophysiology of multiple autoimmune disorders.
      The co-stimulatory molecules SLAMF3 and SLAMF6 have been implicated in the
      formation of Th17 phenotypes and IL-17A expression. Increased surface expression
      of SLAMF3 and SLAMF6 has been linked with disease activity in systemic lupus
      erythematosus. Here we demonstrate that in human total T lymphocytes the
      canonical CD28 and the non-canonical SLAMF3/SLAMF6 co-stimulatory pathways
      cooperate in the recruitment of the transcription factor NFAT1 to the IL17A
      promoter. Furthermore, the dominance of the SLAMF3/SLAMF6 pathway in inducing IL
      17A production can be attributed to an increased nuclear abundance and
      recruitment of RORgammat to the IL17A promoter. Thus, we have identified an
      additional mechanism that may be central for the specific control of IL17A gene
      regulation in systemic lupus erythematosus T lymphocytes.

PMID- 22989875
TI  - Biophysical analysis of Kindlin-3 reveals an elongated conformation and maps
      integrin binding to the membrane-distal beta-subunit NPXY motif.
AB  - Kindlin-3, a 75-kDa protein, has been shown to be critical for hemostasis,
      immunity, and bone metabolism via its role in integrin activation. The Kindlin
      family is hallmarked by a FERM domain comprised of F1, F2, and F3 subdomains
      together with an N-terminal F0 domain and a pleckstrin homology domain inserted
      in the F2 domain. Recombinant Kindlin-3 was cloned, expressed, and purified, and
      its domain organization was studied by x-ray scattering and other techniques to
      reveal an extended conformation. This unusual elongated structure is similar to
      that found in the paralogue Talin head domain. Analytical ultracentrifugation
      experiments indicated that Kindlin-3 forms a ternary complex with the Talin and
      beta-integrin cytoplasmic tails. NMR showed that Kindlin-3 specifically
      recognizes the membrane-distal tail NPXY motif in both the beta(1A) and beta(1D)
      isoforms, although the interaction is stronger with beta(1A). An upstream Ser/Thr
      cluster in the tails also plays a critical role. Overall these data support
      current biological, clinical, and mutational data on Kindlin-3/beta-tail binding
      and provide novel insights into the overall conformation and interactions of
      Kindlin-3.

PMID- 22989876
TI  - Domain organization of the polymerizing mannosyltransferases involved in
      synthesis of the Escherichia coli O8 and O9a lipopolysaccharide O-antigens.
AB  - The Escherichia coli O9a and O8 polymannose O-polysaccharides (O-PSs) serve as
      model systems for the biosynthesis of bacterial polysaccharides by ATP-binding
      cassette transporter-dependent pathways. Both O-PSs contain a conserved primer
      adaptor domain at the reducing terminus and a serotype-specific repeat unit
      domain. The repeat unit domain is polymerized by the serotype-specific WbdA
      mannosyltransferase. In serotype O9a, WbdA is a bifunctional alpha-(1->2)-, alpha
      (1->3)-mannosyltransferase, and its counterpart in serotype O8 is trifunctional
      (alpha-(1->2), alpha-(1->3), and beta-(1->2)). Little is known about the detailed
      structures or mechanisms of action of the WbdA polymerases, and here we establish
      that they are multidomain enzymes. WbdA(O9a) contains two separable and
      functionally active domains, whereas WbdA(O8) possesses three. In WbdC(O9a) and
      WbdB(O9a), substitution of the first Glu of the EX(7)E motif had detrimental
      effects on the enzyme activity, whereas substitution of the second had no
      significant effect on activity in vivo. Mutation of the Glu residues in the
      EX(7)E motif of the N-terminal WbdA(O9a) domain resulted in WbdA variants unable
      to synthesize O-PS. In contrast, mutation of the Glu residues in the motif of the
      C-terminal WbdA(O9a) domain generated an enzyme capable of synthesizing an
      altered O-PS repeat unit consisting of only alpha-(1->2) linkages. In vitro
      assays with synthetic acceptors unequivocally confirmed that the N-terminal
      domain of WbdA(O9a) possesses alpha-(1->2)-mannosyltransferase activity.
      Together, these studies form a framework for detailed structure-function studies
      on individual domains and a strategy applicable for dissection and analysis of
      other multidomain glycosyltransferases.

PMID- 22989877
TI  - A small-molecule screen yields idiotype-specific blockers of neuromyelitis optica
      immunoglobulin G binding to aquaporin-4.
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the
      central nervous system caused by binding of anti-aquaporin-4 (AQP4)
      autoantibodies (NMO-IgG) to AQP4 on astrocytes. A screen was developed to
      identify inhibitors of NMO-IgG-dependent, complement-dependent cytotoxicity.
      Screening of 50,000 synthetic small molecules was done using CHO cells expressing
      human AQP4 and a human NMO recombinant monoclonal antibody (rAb-53). The screen
      yielded pyrano[2,3-c]pyrazoles that blocked rAb-53 binding to AQP4 and prevented
      cytotoxicity in cell culture and spinal cord slice models of NMO. Structure
      activity analysis of 82 analogs yielded a blocker with IC(50) ~ 6 MUm. Analysis
      of the blocker mechanism indicated idiotype specificity, as (i) pyrano[2,3
      c]pyrazoles did not prevent AQP4 binding or cytotoxicity of other NMO-IgGs, and
      (ii) surface plasmon resonance showed specific rAb-53 binding. Antibody structure
      modeling and docking suggested a putative binding site near the complementarity
      determining regions. Small molecules with idiotype-specific antibody targeting
      may be useful as research tools and therapeutics.

PMID- 22989878
TI  - Crystal and solution structures of Plasmodium falciparum erythrocyte-binding
      antigen 140 reveal determinants of receptor specificity during erythrocyte
      invasion.
AB  - Erythrocyte-binding antigen 140 (PfEBA-140) is a critical Plasmodium falciparum
      erythrocyte invasion ligand that engages glycophorin C on host erythrocytes
      during malaria infection. The minimal receptor-binding region of PfEBA-140
      contains two conserved Duffy binding-like (DBL) domains, a fold unique to
      Plasmodium species. Here, we present the crystal structure of the receptor
      binding region of PfEBA-140 at 2.4 A resolution. The two-domain binding region is
      present as a monomer in the asymmetric unit, and the structure reveals novel
      features in PfEBA-140 that are likely determinants of receptor specificity.
      Analysis by small-angle x-ray scattering demonstrated that the minimal binding
      region is monomeric in solution, consistent with the crystal structure.
      Erythrocyte binding assays showed that the full-length binding region containing
      the tandem DBL domains is required for erythrocyte engagement, suggesting that
      both domains contain critical receptor contact sites. The electrostatic surface
      of PfEBA-140 elucidates a basic patch that constitutes a putative high-affinity
      binding interface spanning both DBL domains. Mutation of residues within this
      interface results in severely diminished erythrocyte binding. This study provides
      insight into the structural basis and mechanism of PfEBA-140 receptor engagement
      and forms a basis for future studies of this critical interaction. In addition,
      the solution and crystal structures allow the first identification of likely
      determinants of erythrocyte receptor specificity for P. falciparum invasion
      ligands. A complete understanding of the PfEBA-140 erythrocyte invasion pathway
      will aid in the design of invasion inhibitory therapeutics and vaccines.

PMID- 22989879
TI  - Sialidases on mammalian sperm mediate deciduous sialylation during capacitation.
AB  - Sialic acids (Sias) mediate many biological functions, including molecular
      recognition during development, immune response, and fertilization. A Sia-rich
      glycocalyx coats the surface of sperm, allowing them to survive as allogeneic
      cells in the female reproductive tract despite female immunity. During
      capacitation, sperm lose a fraction of their Sias. We quantified shed Sia
      monosaccharides released from capacitated sperm and measured sperm sialidase
      activity. We report the presence of two sialidases (neuraminidases Neu1 and Neu3)
      on mammalian sperm. These are themselves shed from sperm during capacitation.
      Inhibiting sialidase activity interferes with sperm binding to the zona pellucida
      of the ovum. A survey of human sperm samples for the presence of sialidases NEU1
      and NEU3 identified a lack of one or both sialidases in sperm of some male
      idiopathic infertility cases. The results contribute new insights into the
      dynamic remodeling of the sperm glycocalyx prior to fertilization.

PMID- 22989880
TI  - Secreted Hsp90 is a novel regulator of the epithelial to mesenchymal transition
      (EMT) in prostate cancer.
AB  - Prostate cancer (PCa) is the most frequently diagnosed malignancy in men, and the
      second highest contributor of male cancer related lethality. Disease mortality is
      due primarily to metastatic spread, highlighting the urgent need to identify
      factors involved in this progression. Activation of the genetic epithelial to
      mesenchymal transition (EMT) program is implicated as a major contributor of PCa
      progression. Initiation of EMT confers invasive and metastatic behavior in
      preclinical models and is correlated with poor clinical prognosis. Extracellular
      Hsp90 (eHsp90) promotes cell motility and invasion in cancer cells and metastasis
      in preclinical models, however, the mechanistic basis for its widespread
      tumorigenic function remains unclear. We have identified a novel and pivotal role
      for eHsp90 in driving EMT events in PCa. In support of this notion, more
      metastatic PCa lines exhibited increased eHsp90 expression relative to their
      lineage-related nonmetastatic counterparts. We demonstrate that eHsp90 promoted
      cell motility in an ERK and matrix metalloproteinase-2/9-dependent manner, and
      shifted cellular morphology toward a mesenchymal phenotype. Conversely,
      inhibition of eHsp90 attenuated pro-motility signaling, blocked PCa migration,
      and shifted cell morphology toward an epithelial phenotype. Last, we report that
      surface eHsp90 was found in primary PCa tumor specimens, and elevated eHsp90
      expression was associated with increased levels of matrix metalloproteinase-2/9
      transcripts. We conclude that eHsp90 serves as a driver of EMT events, providing
      a mechanistic basis for its ability to promote cancer progression and metastasis
      in preclinical models. Furthermore, its newly identified expression in PCa
      specimens, and potential regulation of pro-metastatic genes, supports a putative
      clinical role for eHsp90 in PCa progression.

PMID- 22989881
TI  - Post-translational S-nitrosylation is an endogenous factor fine tuning the
      properties of human S100A1 protein.
AB  - BACKGROUND: S100A1 protein is a proposed target of molecule-guided therapy for
      heart failure. RESULTS: S-Nitrosylation of S100A1 is present in cells, increases
      Ca(2+) binding, and tunes the overall protein conformation. CONCLUSION: Thiol
      aromatic molecular switch is responsible for NO-related modification of S100A1
      properties. SIGNIFICANCE: Post-translational S-nitrosylation may provide
      functional diversity and specificity to S100A1 and other S100 protein family
      members. S100A1 is a member of the Ca(2+)-binding S100 protein family. It is
      expressed in brain and heart tissue, where it plays a crucial role as a modulator
      of Ca(2+) homeostasis, energy metabolism, neurotransmitter release, and
      contractile performance. Biological effects of S100A1 have been attributed to its
      direct interaction with a variety of target proteins. The (patho)physiological
      relevance of S100A1 makes it an important molecular target for future therapeutic
      intervention. S-Nitrosylation is a post-translational modification of proteins,
      which plays a role in cellular signal transduction under physiological and
      pathological conditions. In this study, we confirmed that S100A1 protein is
      endogenously modified by Cys(85) S-nitrosylation in PC12 cells, which are a well
      established model system for studying S100A1 function. We used isothermal
      calorimetry to show that S-nitrosylation facilitates the formation of Ca(2+)
      loaded S100A1 at physiological ionic strength conditions. To establish the unique
      influence of the S-nitroso group, our study describes high resolution three
      dimensional structures of human apo-S100A1 protein with the Cys(85) thiol group
      in reduced and S-nitrosylated states. Solution structures of the proteins are
      based on NMR data obtained at physiological ionic strength. Comparative analysis
      shows that S-nitrosylation fine tunes the overall architecture of S100A1 protein.
      Although the typical S100 protein intersubunit four-helix bundle is conserved
      upon S-nitrosylation, the conformation of S100A1 protein is reorganized at the
      sites most important for target recognition (i.e. the C-terminal helix and the
      linker connecting two EF-hand domains). In summary, this study discloses cysteine
      S-nitrosylation as a new factor responsible for increasing functional diversity
      of S100A1 and helps explain the role of S100A1 as a Ca(2+) signal transmitter
      sensitive to NO/redox equilibrium within cells.

PMID- 22989882
TI  - Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis
      via activating reprogramming factors and epithelial-mesenchymal transition gene
      expression in colon cancer.
AB  - Epithelial cell adhesion molecule (EpCAM) is highly expressed in epithelial
      transformed neoplasia and tumor-initiated cells (TICs), but the role that EpCAM
      plays in the stemness properties of TICs is still unclear. Here we show that
      EpCAM and reprogramming factors (c-Myc, Oct4, Nanog, and Sox2) were concomitantly
      elevated in TICs, which were shown to have superior self-renewal, invasiveness,
      and tumor-initiating abilities. Elevation of EpCAM enhanced tumorsphere formation
      and tumor initiation. Knockdown of EpCAM inhibited the expressions of
      reprogramming factors and epithelial-mesenchymal transition genes, thereby
      suppressing tumor initiation, self-renewal, and invasiveness. In addition, EpCAM,
      especially intracellular domain of EpCAM (EpICD), bound to and activated the
      promoter of reprogramming factors. Treatment with the inhibitor of gamma
      secretase (DAPT) led to the blockage of the expressions of reprogramming factors
      and epithelial-mesenchymal transition genes, which was accompanied by the
      reduction of tumor self-renewal and invasion. Furthermore, the increased release
      of EpEX enhanced production of EpICD and regulated the expression of
      reprogramming factors. Together, these findings suggest that EpCAM plays an
      important role in regulating cancer-initiating abilities in TICs of colon cancer.
      This discovery can be used in the development of new strategies for cancer
      therapy.

PMID- 22989883
TI  - Why mouse airway submucosal gland serous cells do not secrete fluid in response
      to cAMP stimulation.
AB  - Airway submucosal glands are important sites of cystic fibrosis transmembrane
      conductance regulator (CFTR) chloride (Cl(-)) channel expression and fluid
      secretion in the airway. Whereas both mouse and human submucosal glands and their
      serous acinar cells express CFTR, human glands and serous cells secrete much more
      robustly than mouse cells/glands in response to cAMP-generating agonists such as
      forskolin and vasoactive intestinal peptide. In this study, we examined mouse and
      human serous acinar cells to explain this difference and reveal further insights
      into the mechanisms of serous cell secretion. We found that mouse serous cells
      possess a robust cAMP-activated CFTR-dependent Cl(-) permeability, but they lack
      cAMP-activated calcium (Ca(2+)) signaling observed in human cells. Similar to
      human cells, basal K(+) conductance is extremely small in mouse acinar cells.
      Lack of cAMP-activated Ca(2+) signaling in mouse cells results in the absence of
      K(+) conductances required for secretion. However, cAMP activates CFTR-dependent
      fluid secretion during low-level cholinergic stimulation that fails to activate
      secretion on its own. Robust CFTR-dependent fluid secretion was also observed
      when cAMP stimulation was combined with direct pharmacological activation of
      epithelial K(+) channels with 1-ethyl-2-benzimidazolinone (EBIO). Our data
      suggest that mouse serous cells lack cAMP-mediated Ca(2+) signaling to activate
      basolateral membrane K(+) conductance, resulting in weak cAMP-driven serous cell
      fluid secretion, providing the likely explanation for reduced cAMP-driven
      secretion observed in mouse compared with human glands.

PMID- 22989884
TI  - Interactions with WNK (with no lysine) family members regulate oxidative stress
      response 1 and ion co-transporter activity.
AB  - Two of the four WNK (with no lysine (K)) protein kinases are associated with a
      heritable form of ion imbalance culminating in hypertension. WNK1 affects ion
      transport in part through activation of the closely related Ste20 family protein
      kinases oxidative stress-responsive 1 (OSR1) and STE20/SPS1-related proline-,
      alanine-rich kinase (SPAK). Once activated by WNK1, OSR1 and SPAK phosphorylate
      and stimulate the sodium, potassium, two chloride co-transporters, NKCC1 and
      NKCC2, and also affect other related ion co-transporters. We find that WNK1 and
      OSR1 co-localize on cytoplasmic puncta in HeLa and other cell types. We show that
      the C-terminal region of WNK1 including a coiled coil is sufficient to localize
      the fragment in a manner similar to the full-length protein, but some other
      fragments lacking this region are mislocalized. Photobleaching experiments
      indicate that both hypertonic and hypotonic conditions reduce the mobility of GFP
      WNK1 in cells. The four WNK family members can phosphorylate the activation loop
      of OSR1 to increase its activity with similar kinetic constants. C-terminal
      fragments of WNK1 that contain three RFXV interaction motifs can bind OSR1, block
      activation of OSR1 by sorbitol, and prevent the OSR1-induced enhancement of ion
      co-transporter activity in cells, further supporting the conclusion that
      association with WNK1 is required for OSR1 activation and function at least in
      some contexts. C-terminal WNK1 fragments can be phosphorylated by OSR1,
      suggesting that OSR1 catalyzes feedback phosphorylation of WNK1.

PMID- 22989885
TI  - Activation of cannabinoid receptor type 1 (Cb1r) disrupts hepatic insulin
      receptor signaling via cyclic AMP-response element-binding protein H (Crebh)
      mediated induction of Lipin1 gene.
AB  - Activation of hepatic cannabinoid 1 receptor (Cb1r) signaling has been implicated
      in the development of phenotypes associated with fatty liver,
      hypertriglyceridemia, and insulin resistance. In the current study, we have
      elucidated the critical role of endoplasmic reticulum-bound transcription factor
      cyclic AMP-response element-binding protein H (Crebh) in mediating activated Cb1r
      signaling in inducing phosphatidic acid phosphatase Lipin1 gene expression and
      subsequently deregulating hepatic insulin receptor signaling. Cb1r agonist (2
      arachidonoylglycerol (2-AG)) treatment induced Lipin1 gene expression in a Crebh
      dependent manner via recruiting CREBH to the endogenous Lipin1 gene promoter.
      Adenoviral overexpression of Crebh or 2-AG treatment in mice induced Lipin1 gene
      expression to increase the hepatic diacylglycerol (DAG) level and phosphorylation
      of protein kinase Cepsilon (PKCepsilon). This in turn inhibited hepatic insulin
      receptor signaling. Knockdown of Crebh or Cb1r antagonism attenuated 2-AG
      mediated induction of Lipin1 gene expression and decreased DAG production in
      mouse liver and subsequently restored insulin receptor signaling. Similarly,
      knockdown of Lipin1 attenuated the 2-AG-induced increase in the DAG level and
      PKCepsilon phosphorylation. Finally, shRNA-mediated knockdown of Crebh partially
      but significantly blunted Lipin1 expression and the DAG level in db/db mice.
      These results demonstrate a novel mechanism by which Cb1r signaling induces
      Lipin1 gene expression and increases DAG production by activating Crebh, thereby
      deregulating insulin receptor signaling pathway and lipid homeostasis.

PMID- 22989886
TI  - Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering
      drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome
      proliferator-activated receptor alpha: implications for late infantile Batten
      disease therapy.
AB  - The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an
      autosomal recessive disease, where the defective gene is Cln2, encoding
      tripeptidyl-peptidase I (TPP1). At the molecular level, LINCL is caused by
      accumulation of autofluorescent storage materials in neurons and other cell
      types. Currently, there is no established treatment for this fatal disease. This
      study reveals a novel use of gemfibrozil and fenofibrate, Food and Drug
      Administration-approved lipid-lowering drugs, in up-regulating TPP1 in brain
      cells. Both gemfibrozil and fenofibrate up-regulated mRNA, protein, and enzymatic
      activity of TPP1 in primary mouse neurons and astrocytes as well as human
      astrocytes and neuronal cells. Because gemfibrozil and fenofibrate are known to
      activate peroxisome proliferator-activated receptor-alpha (PPARalpha), the role
      of PPARalpha in gemfibrozil- and fenofibrate-mediated up-regulation of TPP1 was
      investigated revealing that both drugs up-regulated TPP1 mRNA, protein, and
      enzymatic activity both in vitro and in vivo in wild type (WT) and PPARbeta(-/-),
      but not PPARalpha(-/-), mice. In an attempt to delineate the mechanism of TPP1 up
      regulation, it was found that the effects of the fibrate drugs were abrogated in
      the absence of retinoid X receptor-alpha (RXRalpha), a molecule known to form a
      heterodimer with PPARalpha. Accordingly, all-trans-retinoic acid, alone or
      together with gemfibrozil, up-regulated TPP1. Co-immunoprecipitation and ChIP
      studies revealed the formation of a PPARalpha/RXRalpha heterodimer and binding of
      the heterodimer to an RXR-binding site on the Cln2 promoter. Together, this study
      demonstrates a unique mechanism for the up-regulation of TPP1 by fibrate drugs
      via PPARalpha/RXRalpha pathway.

PMID- 22989887
TI  - Intrinsic flexibility of ubiquitin on proliferating cell nuclear antigen (PCNA)
      in translesion synthesis.
AB  - Ubiquitin conjugation provides a crucial signaling role in hundreds of cellular
      pathways; however, a structural understanding of ubiquitinated substrates is
      lacking. One important substrate is monoubiquitinated PCNA (PCNA-Ub), which
      signals for recruitment of damage-tolerant polymerases in the translesion
      synthesis (TLS) pathway of DNA damage avoidance. We use a novel and efficient
      enzymatic method to produce PCNA-Ub at high yield with a native isopeptide bond
      and study its Usp1/UAF1-dependent deconjugation. In solution we find that the
      ubiquitin moiety is flexible relative to the PCNA, with its hydrophobic patch
      mostly accessible for recruitment of TLS polymerases, which promotes the
      interaction with polymerase eta. The studies are a prototype for the nature of
      the ubiquitin modification.

PMID- 22989888
TI  - DNA sequence context effects on the glycosylase activity of human 8-oxoguanine
      DNA glycosylase.
AB  - Human 8-oxoguanine DNA glycosylase (OGG1) is a key enzyme involved in removing
      7,8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic DNA lesion generated by
      oxidative stress. The removal of 8-oxoG by OGG1 is affected by the local DNA
      sequence, and this feature most likely contributes to observed mutational hot
      spots in genomic DNA. To elucidate the influence of local DNA sequence on 8-oxoG
      excision activity of OGG1, we conducted steady-state, pre-steady-state, and
      single turnover kinetic evaluation of OGG1 in alternate DNA sequence contexts.
      The sequence context effect was studied for a mutational hot spot at a CpG
      dinucleotide. Altering either the global DNA sequence or the 5'-flanking
      unmodified base pair failed to influence the excision of 8-oxoG. Methylation of
      the cytosine 5' to 8-oxoG also did not affect 8-oxoG excision. In contrast, a 5'
      neighboring mismatch strongly decreased the rate of 8-oxoG base removal.
      Substituting the 5'-C in the CpG dinucleotide with T, A, or tetrahydrofuran (i.e.
      T:G, A:G, and tetrahydrofuran:G mispairs) resulted in a 10-, 13-, and 4-fold
      decrease in the rate constant for 8-oxoG excision, respectively. A greater loss
      in activity was observed when T:C or A:C was positioned 5' of 8-oxoG (59- and 108
      fold, respectively). These results indicate that neighboring structural
      abnormalities 5' to 8-oxoG deter its repair thereby enhancing its mutagenic
      potential.

PMID- 22989889
TI  - Prothrombin activation by platelet-associated prothrombinase proceeds through the
      prethrombin-2 pathway via a concerted mechanism.
AB  - The protease alpha-thrombin is a key enzyme of the coagulation process as it is
      at the cross-roads of both the pro- and anti-coagulant pathways. The main source
      of alpha-thrombin in vivo is the activation of prothrombin by the prothrombinase
      complex assembled on either an activated cell membrane or cell fragment, the most
      relevant of which is the activated platelet surface. When prothrombinase is
      assembled on synthetic phospholipid vesicles, prothrombin activation proceeds
      with an initial cleavage at Arg-320 yielding the catalytically active, yet
      effectively anticoagulant intermediate meizothrombin, which is released from the
      enzyme complex ~30-40% of the time. Prothrombinase assembled on the surface of
      activated platelets has been shown to proceed through the inactive intermediate
      prethrombin-2 via an initial cleavage at Arg-271 followed by cleavage at Arg-320.
      The current work tests whether or not platelet-associated prothrombinase proceeds
      via a concerted mechanism through a study of prothrombinase assembly and function
      on collagen-adhered, thrombin-activated, washed human platelets in a flow
      chamber. Prothrombinase assembly was demonstrated through visualization of bound
      factor Xa by confocal microscopy using a fluorophore-labeled anti-factor Xa
      antibody, which demonstrated the presence of distinct platelet subpopulations
      capable of binding factor Xa. When prothrombin activation was monitored at a
      typical venous shear rate over preassembled platelet-associated prothrombinase
      neither potential intermediate, meizothrombin or prethrombin-2, was observed in
      the effluent. Collectively, these findings suggest that platelet-associated
      prothrombinase activates prothrombin via an efficient concerted mechanism in
      which neither intermediate is released.

PMID- 22989891
TI  - Long-term video-EEG in patients with frontal seizures.
AB  - The interictal epileptiform discharge (IED) yield of long-term video-EEG (LTVEEG)
      monitoring is increased compared to a single out-patient EEG, but was not studied
      specifically in frontal lobe epilepsy. Since IED recording can influence the
      length of monitoring when seizures are not  recorded during LTVEEG, we aimed to
      assess the IED yield of LTVEEG recording in patients with frontal seizures. We
      retrospectively reviewed the medical records of 20 patients with frontal seizures
      during non-invasive LTVEEG in Tel Aviv Medical Center between 2003 and 2008 and
      compared them  with the results of out-patient EEG. The study group included 11
      (55%) men and 9 women aged 15-82 years (mean: 27 years). LTVEEG duration ranged
      between 4 and 29 days (mean: 14 days). IEDs were detected by each of the tests in
      eight (40%) patients. We conclude that non-invasive LTVEEG  and out-patient EEG
      have a similar diagnostic yield for IEDs in patients with frontal seizures.
      Therefore, seizures remain the most relevant clinical outcome of LTVEEG.

PMID- 22989892
TI  - Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a
      multicenter retrospective analysis.
AB  - BACKGROUND: Chronic pancreatitis is suggested to be one of the risk factors for
      the development of pancreatic cancer. The aim of this study was to confirm the
      high incidence of pancreatic cancer in patients with chronic pancreatitis in
      Japan and to determine the factors associated with the risk for pancreatic cancer
      in patients with chronic pancreatitis. METHODS: The working group of the Research
      Committee of Intractable Disease supported by the Ministry of Health, Labour and
      Welfare of Japan carried out a nationwide survey to investigate the relationship
      between chronic pancreatitis and pancreatic cancer. This retrospective study
      included patients diagnosed with chronic pancreatitis who had had at least 2
      years of follow-up. They were contacted through 22 Japanese referral centers
      experienced in the management of chronic pancreatitis. RESULTS: The standardized
      incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence
      of pancreatic cancer was significantly lower in patients who had received surgery
      for chronic pancreatitis than in those who had not undergone surgery (hazard
      ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients
      who continued to drink alcohol after diagnosis of chronic pancreatitis showed a
      significantly higher incidence of pancreatic cancer than those who stopped
      drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI,
      1.13-22.73; P = .03). CONCLUSION: This study confirmed that chronic pancreatitis
      is an important risk factor for the development of pancreatic cancer in Japan.
      Patients who underwent surgery for the treatment of chronic pancreatitis had
      significantly lower incidences of pancreatic cancer. Surgery for chronic
      pancreatitis may inhibit the development of pancreatic cancer in patients with
      chronic pancreatitis.

PMID- 22989890
TI  - 14-3-3zeta Protein regulates anterograde transport of the human kappa-opioid
      receptor (hKOPR).
AB  - By proteomic analysis, we found that 14-3-3zeta was one of the proteins co
      immunoprecipitated with human kappa-opioid receptor (hKOPR) from extracts of
      solubilized Neuro2A cells stably expressing FLAG-hKOPR (N2A-FLAG-hKOPR cells). 14
      3-3 proteins are a family of conserved regulatory molecules in eukaryotic cells,
      where they participate in signal transduction, metabolism, and membrane protein
      transport. 14-3-3zeta co-localized with the hKOPR in N2A cells. The hKOPR C-tail
      interacted with 14-3-3zeta in rat brain extracts and bound directly to purified
      14-3-3zeta as demonstrated by pulldown techniques. 14-3-3zeta siRNA decreased
      expression of the hKOPR in N2A-FLAG-hKOPR cells and cultured primary cortical
      neurons of E19 rats by ~25% as determined by immunoblotting, ligand binding, and
      flow cytometry. The effect of 14-3-3zeta siRNA was reversed by overexpression of
      14-3-3zeta. Expression of the 14-3-3 scavenger protein pGpLI-R18 also decreased
      hKOPR expression. 14-3-3zeta siRNA did not change expressions of the hDOPR and
      rMOPR in N2A cells. Pulse-chase study showed that 14-3-3zeta siRNA decreased the
      amount of mature hKOPR but did not change the rate of maturation or stability of
      hKOPR protein. Mutations of R354A/S358A in the putative 14-3-3 interaction motif
      (354)RQSTS(358) in the hKOPR C-tail reduced interaction of the hKOPR with 14-3
      3zeta and abolished the effect of 14-3-3zeta knockdown on hKOPR expression.
      Mutation of the endoplasmic reticulum retention motif (359)RVR adjacent to the 14
      3-3 interaction motif in the hKOPR C-tail decreased interaction of coatomer
      protein I (COPI) with the hKOPR and abolished 14-3-3zeta-mediated regulation of
      hKOPR expression. 14-3-3zeta knockdown increased association of COPI with the
      hKOPR. These results suggest that 14-3-3zeta promotes expression of the hKOPR by
      inhibiting COPI and RVR motif-mediated endoplasmic reticulum localization
      machinery.

PMID- 22989893
TI  - A cost-effectiveness analysis of adrenalectomy for nonfunctional adrenal
      incidentalomas: is there a size threshold for resection?
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare, but aggressive, malignancy.
      Current American Association of Clinical Endocrinologists (AACE)/American
      Association of Endocrine Surgeons (AAES) guidelines recommend resection of
      nonfunctional adrenal neoplasms >= 4 cm. This study evaluates the cost
      effectiveness of this approach. METHODS: A decision tree was constructed for
      patients with a nonfunctional, 4-cm adrenal incidentaloma with no radiographic
      suspicion for ACC. Patients were randomized to adrenalectomy, surveillance per
      AACE/AAES guidelines, or no follow-up ("sign-off"). Incremental cost
      effectiveness ratio (ICER) includes health care costs, including missed ACC. ICER
      (dollar/life-year-saved [LYS]) was determined from the societal perspective.
      Sensitivity analyses were performed. RESULTS: In the base-case analysis, assuming
      a 2.0% probability of ACC for a 4-cm tumor, surgery was more cost-effective than
      surveillance (ICER $25,843/LYS). Both surgery and surveillance were incrementally
      more cost-effective than sign-off ($35/LYS and $8/LYS, respectively). Sensitivity
      analysis demonstrated that the model was sensitive to patient age, tumor size,
      probability of ACC, mortality of ACC, and cost of hospitalization. The results of
      the model were stable across different cost and complications related to
      adrenalectomy, regardless of operative approach. CONCLUSION: In our model,
      adrenalectomy was cost-effective for neoplasms >4 cm and in patients <65 years,
      primarily owing to the aggressiveness of ACC. Current AACE/AAES guideline
      recommendations for the resection of adrenal incidentalomas >= 4 cm seem to be
      cost-effective.

PMID- 22989894
TI  - Smartphone versus pen-and-paper data collection of infant feeding practices in
      rural China.
AB  - BACKGROUND: Maternal, Newborn, and Child Health (MNCH) household survey data are
      collected mainly with pen-and-paper. Smartphone data collection may have
      advantages over pen-and-paper, but little evidence exists on how they compare.
      OBJECTIVE: To compare smartphone data collection versus the use of pen-and-paper
      for infant feeding practices of the MNCH household survey. We compared the two
      data collection methods for differences in data quality (data recording, data
      entry, open-ended answers, and interrater reliability), time consumption, costs,
      interviewers' perceptions, and problems encountered. METHODS: We recruited
      mothers of infants aged 0 to 23 months in four village clinics in Zhaozhou
      Township, Zhao County, Hebei Province, China. We randomly assigned mothers to a
      smartphone or a pen-and-paper questionnaire group. A pair of interviewers
      simultaneously questioned mothers on infant feeding practices, each using the
      same method (either smartphone or pen-and-paper). RESULTS: We enrolled 120
      mothers, and all completed the study. Data recording errors were prevented in the
      smartphone questionnaire. In the 120 pen-and-paper questionnaires (60 mothers),
      we found 192 data recording errors in 55 questionnaires. There was no significant
      difference in recording variation between the groups for the questionnaire pairs
      (P = .32) or variables (P = .45). The smartphone questionnaires were
      automatically uploaded and no data entry errors occurred. We found that even
      after double data entry of the pen-and-paper questionnaires, 65.0% (78/120) of
      the questionnaires did not match and needed to be checked. The mean duration of
      an interview was 10.22 (SD 2.17) minutes for the smartphone method and 10.83 (SD
      2.94) minutes for the pen-and-paper method, which was not significantly different
      between the methods (P = .19). The mean costs per questionnaire were higher for
      the smartphone questionnaire (Y143, equal to US $23 at the exchange rate on April
      24, 2012) than for the pen-and-paper questionnaire (Y83, equal to US $13). The
      smartphone method was acceptable to interviewers, and after a pilot test we
      encountered only minor problems (eg, the system halted for a few seconds or it
      shut off), which did not result in data loss. CONCLUSIONS: This is the first
      study showing that smartphones can be successfully used for household data
      collection on infant feeding in rural China. Using smartphones for data
      collection, compared with pen-and-paper, eliminated data recording and entry
      errors, had similar interrater reliability, and took an equal amount of time per
      interview. While the costs for the smartphone method were higher than the pen-and
      paper method in our small-scale survey, the costs for both methods would be
      similar for a large-scale survey. Smartphone data collection should be further
      evaluated for other surveys and on a larger scale to deliver maximum benefits in
      China and elsewhere.

PMID- 22989895
TI  - Ontogeny of cocaine- and amphetamine-regulated transcript peptide in brain of
      frog, Microhyla ornata.
AB  - The cocaine- and amphetamine-regulated transcript (CART) peptide is widely
      distributed in the brains of adult vertebrates including amphibians. Several
      physiological roles of CART have been intensely investigated in mammals. Despite
      these studies, the expression of CART during development of brain has not been
      studied in amphibians. In the present study, distribution of CART was
      investigated during development in the post hatched stage 23 to premetamorphic
      stage 30 of frog Microhyla ornata. CART is expressed as early as in stage 23 in
      ventral thalamus and rhombencephalon. As development progressed, CART
      immunoreactivity was observed in the olfactory bulb, telencephalon,
      rhombencephalon and spinal cord in stage 24. At stage 25, the CART
      immunoreactivity was observed in the ventromedial thalamic nucleus,
      posterocentral thalamic nucleus, torus nucleus, central gray and inferior
      reticular nucleus. In stage 26, CART reactivity was seen in the medial septum,
      preoptic area, nucleus entopeduncularis, magnocellular nucleus, median eminence,
      optic tectum, hypophysis and cerebellum. Additionally, CART immunoreactivity was
      observed in the medial pallium, anterior commissure, nucleus infundibularis
      dorsalis, ventralis and raphe nucleus at stage 30. The occurrences of CART
      immunoreactivity at early stage of development suggest that the peptide may have
      a functional significance during development. The wider appearance of CART in the
      brain of tadpoles, M. ornata suggests that the peptide may act as a neurohormone
      during the ontogeny.

PMID- 22989896
TI  - PtdIns(4,5)P2 interacts with CaM binding domains on TRPM3 N-terminus.
AB  - TRPM3 has been reported to play an important role in Ca(2+) homeostasis, but its
      gating mechanisms and regulation via Ca(2+) are unknown. Ca(2+) binding proteins
      such as calmodulin (CaM) could be probable modulators of this ion channel. We
      have shown that this protein binds to two independent domains, A35-K124 and H291
      G382 on the TRPM3 N-terminus, which contain conserved hydrophobic as well as
      positively charged residues in specific positions, and that these residues have a
      crucial impact on its binding. We also showed that the other Ca(2+) binding
      protein, S100A1, is able to bind to these regions and that CaM and S100A1 compete
      for these binding sites on the TRPM3 N-terminus. Moreover, our results suggest
      that another very important TRP channel activity modulator, PtdIns(4,5)P(2),
      interacts with the CaM/S100A1 binding sites on the TRPM3 N-terminus with high
      affinity.

PMID- 22989897
TI  - [Clinical features and courses in patients with new-onset epileptic convulsive
      seizure: comparison of elderly with non-elderly].
AB  - We retrospectively studied the clinical features and the outcome of first acute
      symptomatic seizure in elderly. The subjects were 457 patients, who were more
      than 15 years old, and whose electroencephalograms were available in our
      hospital. The subjects were divided into two groups, the elderly (236 patients;
      age more than 60 years, mean age; 73.2+/-8.2, 105 female, 131 men), and non
      elderly (221 patients; 15<=age<=59, mean age; 35.7+/-14.1, 87 female, 134 men),
      and were diagnosed in accordance with the guidelines of ILAE. We ascertained all
      episodes of acute symptomatic seizure and unprovoked seizure. Date on age,
      gender, etiology, status epilepticus (SE), 30-day and one-year mortalities, and
      subsequent episodes of unprovoked seizure were collected. Acute symptomatic
      seizures are more likely to occur in elderly group, and showed higher short-/and
      long-term mortalities than unprovoked seizures in both elderly and non-elderly
      groups. Acute symptomatic seizures due to multiple causes in elderly group showed
      the highest mortality. The outcome of patient who had SE was poorer within 30
      days, but not within one year among 30-day survivors. Considering the fact that
      first seizures in the elderly are likely to be provoked by acute illnesses, we
      need to take special care in diagnosing and treating them.

PMID- 22989898
TI  - [Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-II at Japan
      site: study design and advance construction of domestic research network].
AB  - The Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH)-II Trial
      (ClinicalTrials.gov no. NCT01176565; (UMIN 000006526) is an international,
      multicenter, randomized, concurrently-controlled, parallel arm, Phase III trial
      to determine the therapeutic benefit of early intensive systolic blood pressure
      (SBP) lowering compared with standard SBP lowering for acute hypertension in
      patients with spontaneous intracerebral hemorrhage (ICH). The Trial is funded by
      the National Institutes of Health in the United States and led by Dr. Adnan
      Qureshi at the University of Minnesota. Seventeen Japanese institutions will
      participate in this Trial. This article describes the latest version of the study
      design and our endeavors to develop the Japanese research network for stroke
      clinical research. The ATACH-II Trial plans to randomize a maximum of 1,280
      (approximately 400 from Japan) subjects who have supratentorial ICH (hematoma
      volume <60cc) with Glasgow Coma Scale >=5 and SBP of >180mmHg. Subjects undergo a
      follow-up assessment for functional and quality of life assessment at 90 days
      post-randomization. The primary research hypothesis of the trial is that
      intensive SBP reduction (to <=140mmHg) using intravenous nicardipine infusion for
      24 hours post-randomization reduces the proportion of death and disability at 90
      days by >=10% (absolute) compared to the standard SBP reduction (to 140-180mmHg
      range) among subjects with ICH whose treatment is initiated within 4.5 hours of
      symptom onset. The ATACH-II Trial could be the seminal research project for
      stroke researchers in Japan to demonstrate themselves as effective contributing
      members of investigator-initiated international clinical trials.

PMID- 22989899
TI  - [The medial temporal area and parietal lobe are involved in epileptic polyopia
      and palinopsia: A case report].
AB  - This report presents the case of an 83-year-old female with a tumor in the right
      temporal lobe. She experienced various epileptic visual auras including visual
      perseveration. Visual perseveration is classified into polyopia and palinopsia.
      Epileptic visual perseveration is a rare phenomenon, and the mechanism has not
      been fully explained. MRI revealed a tumor in the right temporal lobe with edema
      in the occipital white matter. To reveal mechanisms of epileptic polyopia and
      palinopsia, we recorded EEG and (123)I-IMP-SPECT when she experienced epileptic
      attacks. EEG showed epileptic discharges beginning at the occipital area, which
      spread to the temporal and parietal areas. During the EEG recording, the main
      symptom was an unformed hallucination. SPECT showed that blood flow increased in
      the right medial temporal and parietal lobes and, to a slightly lesser extent, in
      the right occipito-temporal area when the polyopia and palinopsia frequently
      appeared. Involvement of the multiple foci may have caused the different kinds of
      visual symptoms. The medial temporal and parietal areas were likely responsible
      for polyopia and palinopsia at least for this patient.

PMID- 22989900
TI  - [Case of Bickerstaff brainstem encephalitis associated with spindle coma and
      decorticate posture].
AB  - A 25-years-old man experienced fever and diarrhea. Ten days later he noticed
      difficulty walking (day 1). On admission neurological examination revealed
      lethargy, dysarthria and weakness of limbs. Oculocephalic response was not be
      elicited and extensor toe signs were positive. In spite of treatment with
      aciclovir and methylprednisolone, he continued to show progressive deterioration
      developing to coma with decorticate posture. Autonomic symptoms (hyperhidrosis,
      hypersalivation and fever) and groaning were observed. Brain magnetic resonance
      image and brainstem evoked potential presented no abnormality, but
      electroencephalographic study showed a spindle pattern indicating spindle coma.
      Laboratory tests including cerebrospinal fluids showed no specific results. High
      dose immunoglobulin was administered from day 6, and his consciousness level
      improved. External ophthalomoplegia and ataxic gait were observed after he became
      more alert. Because he had IgG type anti-GQ1b antibodies in the serum, a
      diagnosis was made of Bickerstaff's brainstem encephalitis (BBE). Six months
      after discharge he had complete resolution of his symptoms. This is the first
      report of spindle coma observed in a case of serologically confirmed BBE.

PMID- 22989901
TI  - [Clinicopathologic findings of argyrophilic-grain dementia in a case of mild
      cognitive impairment converting to dementia].
AB  - An 84-year-old Japanese woman with no family history of dementia visited our
      memory clinic complaining of memory disturbance. Neurological examination
      revealed no apparent motor abnormalities, focal cerebral signs, parkinsonism, or
      cerebellar dysfunction. Hasegawa's Dementia Scale-Revised (HDS-R) and Mini mental
      state examination (MMSE) scores were 24 and 23 points, respectively. MRI revealed
      left-side-dominant dilatation of the inferior horn of the lateral ventricle.
      Although egocentric behavior was remarkable, no disturbance of intelligence was
      apparent at the first examination, and she was diagnosed as having mild cognitive
      impairment. Her memory disturbance and disorientation gradually worsened. Atrophy
      of the cerebrum and dilatation of the lateral ventricle advanced gradually on
      MRI. Two years later, she required care to perform activities of daily living.
      HDS-R and MMSE scores had dropped to 13 and 18 points, respectively, and
      conversion to dementia was diagnosed. Ability to perform 3D cube-copying was well
      preserved. The patient died due to acute myocardial infarction at the age of 87.
      The clinical diagnosis was Alzheimer disease. At autopsy, the brain weighed
      1,250g, and argyrophilic grains were widely observed in the limbic system,
      corresponding to Saito's stage III. Neuron loss, gliosis, spongiform change, and
      tissue rarefaction were recognized in the superficial layer of the
      parahippocampal gyrus. Ballooned neurons, pretangles, oligodendroglial coiled
      bodies, and neuropil threads were also observed. Neurofibrillary tangles and
      senile plaques, mainly consisting of diffuse plaque, were recognized as
      corresponding to Braak stage III and CERAD stage B, respectively. Neither Lewy
      nor Pick bodies were observed. Although mild phosphorylated TDP-43
      immunoreactivity was observed, it was suspected to be due to secondary
      degeneration of tau deposition. The patient was diagnosed pathologically as
      having argyrophilic grain dementia. The clinical findings of the present patient
      reveal important observations that help to clinically discriminate between
      various dementias such as Alzheimer disease and argyrophilic grain dementia.

PMID- 22989902
TI  - [Anti-Ma2, anti-NMDA-receptor and anti-GluRepsilon2 limbic encephalitis with
      testicular seminoma: short-term memory disturbance].
AB  - A 36-year-old man presented with cognitive impairment and disturbance of short
      term memory functions with character change. Cerebrospinal fluid analysis
      revealed no abnormalities; however, brain MRI revealed high-signal intensity from
      bilateral hippocampus lesions on fluid attenuated inversion recovery (FLAIR)
      images and T(2) weighted images. The 18F-fluorodeoxyglucose PET demonstrated high
      glucose uptake in the bilateral hippocampus lesions. He was diagnosed as limbic
      encephalitis, and was administered high-dose intravenous methylprednisolone and
      immune adsorption plasma therapy followed by intravenous immunoglobulin therapy.
      MRI abnormalities improved after treatment but recent memory disturbance
      remained. Ma2 antibody, NMDA-receptor antibody, and GluRepsilon2 antibody were
      positive. Eleven months atter the onset of disease, the tumor was identified in
      left testicle by ultrasound and removed the tumor. The pathological findings were
      seminoma. We experienced a case of paraneoplastic limbic encephalitis associated
      with seminoma with short-term memory disturbance. The occurrence of
      paraneoplastic limbic encephalitis with antibodies against cell membrane (NMDA
      receptor antibody and GluRepsilon2 antibody) and intracellular (Ma2 antibody) is
      rare even in the literature.

PMID- 22989903
TI  - [Delayed posthypoxic leukoencephalopathy: case reports].
AB  - Delayed posthypoxic leukoencephalopathy (DPL) is a rare and less well known
      complication of hypoxic brain injury. Although it is well known that anoxic or
      hypoxic injury produces acute neurologic deficits, DPL typically manifests days
      to weeks after apparent recovery from an obtunded state, and patients with DPL
      demonstrate cognitive impairment, high brain dysfunction, parkinsonism, or
      psychosis. MRI findings of the brain demonstrate deep white matter abnormalities.
      We report 2 cases of DPL after hypoxia due to benzodiazepine overdose. Both of
      our patients had normal arylsulfatase A activity. Although DPL is seen in carbon
      monoxide poisoning, pseudodeficiency of arylsulfatase A activity, or drug
      overdose with heroin or morphine, there are only some previous studies of DPL
      caused by an overdose with benzodiazepine. It is unclear whether neurotoxicity
      from the drug in addition to hypoxia alone is involved, however, it is important
      to note that overdose of common drugs as sleeping medicine can cause DPL. Since
      DPL may often be misdiagnosed and be subjected to unnecessary treatments, it is
      also important to understand its unique clinical course and MRI findings. With
      prompt recognition of DPL, we expect that more cases of DPL caused by overdose
      with benzodiazepine will be diagnosed, because benzodiazepine overdoses are
      common.

PMID- 22989904
TI  - [Case of anti VGKC-complex antibody associated disorder presenting with severe
      pain and fasciculations predominant in unilateral upper extremity].
AB  - A 21-year-old man complained of severe pain and muscle twitching localized in his
      right arm. Neurological examination showed muscle fasciculations in his right
      forearm but no myokymia or myotonia. Needle electromyography revealed
      fibrillation potentials in his biceps brachii muscle and extensor carpi radialis
      muscle at rest but no myokymic discharges. His serum anti-voltage-gated potassium
      channel (VGKC)-complex antibody level was significantly high (194.2pM; controls
      <100pM). Although anticonvulsant therapy relieved his pain, he was readmitted to
      our hospital because of severe pain in his left arm and both thighs three months
      later. A high-dose intravenous immunoglobulin (IVIG) therapy followed by steroid
      pulse therapy relieved his pain. This case with neither muscle cramp nor myokymia
      expands the phenotype of anti VGKC-complex antibody associated disorder.

PMID- 22989905
TI  - [A 68 year-old man presenting ideomotor apraxia and incomplete Gerstmann syndrome
      with multiple cystic lesions in the left hemisphere].
AB  - A 68-year-old man was referred to our hospital with tension-type headaches and a
      1-year history of dementia. On neurologic examination, he had ideomotor apraxia
      and incomplete Gerstmann syndrome that was characterized by acalculia, agraphia,
      and finger agnosia. On imaging, multiple cystic lesions reported as "unusually
      dilated perivascular spaces" were observed along the medullary arteries in the
      left hemisphere; some of them had adjacent hyperintense areas in fluid attenuated
      inversion recovery images. We assumed that the multiple cystic lesions caused his
      higher cerebral dysfunction, because ideomotor apraxia and Gerstmann syndrome are
      usually indicative of a left parietal lobe lesion. MR spectroscopy in the lesion
      site revealed increased lactate. On MR angiography, the left middle cerebral
      artery and the left posterior cerebral artery were poorly visualized without
      localized stenosis. Technetium-99 bicisate single-photon emission computed
      tomography showed severely decreased cerebral blood flow in the left hemisphere.
      Electroencephalography showed slow waves in the left hemisphere.

PMID- 22989906
TI  - [Complete atrioventricular block in Duchenne muscular dystrophy].
AB  - We report a case of complete atrioventricular (AV) block in a 40-year-old patient
      with Duchenne muscular dystrophy (DMD). While he was bed-ridden and required
      mechanical ventilation, his cardiac involvement was mild. He had the deletion of
      exon 45-52 in the dystrophin gene. He underwent transient complete AV block and
      came to require pacemaker implantation due to recurrence of complete AV block ten
      days after the first attack. Electrophysiological study revealed mild prolonged
      AH and HV interval. Although DMD patients with AV block have been rarely reported
      so far, attention should be paid to AV block for patients who prolonged their
      lives.

PMID- 22989907
TI  - 'Inverted' analogs of the antibiotic gramicidin S with an improved biological
      profile.
AB  - A series of gramicidin S derivatives 4-15 are presented that have four ornithine
      residues as polar protonated side chains and two central hydrophobic amino acids
      with unaltered turn regions. These peptides were screened against human
      erthrocytes and our standard panel of Gram negative- and Gram positive bacteria,
      including four MRSA strains. Based on the antibacterial- and hemolytic data,
      peptides 13 and 14 have an improved biological profile compared to the clinically
      applied topical antibiotic gramicidin S.

PMID- 22989908
TI  - RNA-based diagnosis in a multicellular specimen by whole mount in situ
      hybridization using an RNA-specific probe.
AB  - Recent RNA research has revealed the close involvement of various RNAs in
      cellular functions. RNAs are becoming the inevitable target molecules for
      research into details of gene expression. RNA and its related complexes are also
      promising targets for disease diagnosis. Multi cellular specimens such as organ
      tissues, histopathological specimens, and embryos are among the possible targets
      of RNA-based diagnostic techniques. In this report, we focused on a method that
      would provide such spatial and temporal information. We demonstrated that an RNA
      specific probe (OMUpy2) was not only applicable to the detection of a specific
      mRNA in Drosophila embryos in a temporal and spatial manner but was also
      relatively quick and easy to use. The probe, OMUpy2, could be applied to other
      multi cellular systems for RNA-based diagnosis and research. The promising
      results of this manuscript show the great potential of RNA-based detection for
      both biological research and diagnostic medicine.

PMID- 22989909
TI  - Novel fluorescent ceramide derivatives for probing ceramidase substrate
      specificity.
AB  - Ceramidases are key regulators of cell fate. The biochemistry of different
      ceramidases and of their substrate ceramide appears to be complex, mainly due to
      specific biophysical characteristics at the water-membrane interface. In the
      present study, we describe the design and synthesis of a set of fluorescently
      labeled ceramides as substrates for acid and neutral ceramidases. For the first
      time we have replaced the commonly used polar NBD-dye with the lipophilic Nile
      Red (NR) dye. Analysis of kinetic data reveal that although both the dyes do not
      have any noticeable preference for the substitution at acyl or sphingosine (Sph)
      part in ceramide towards hydrolysis by acid ceramidase, the ceramides with acyl
      substituted NBD and Sph-substituted NR dyes have been found to be a better
      substrate for neutral ceramidase.

PMID- 22989911
TI  - Synthesis and CYP26A1 inhibitory activity of novel methyl 3-[4-(arylamino)phenyl]
      3-(azole)-2,2-dimethylpropanoates.
AB  - The role of all-trans-retinoic acid (ATRA) in the development and maintenance of
      many epithelial and neural tissues has raised great interest in the potential of
      ATRA and related compounds (retinoids) as pharmacological agents, particularly
      for the treatment of cancer, skin, neurodegenerative and autoimmune diseases. The
      use of ATRA or prodrugs as pharmacological agents is limited by a short half-life
      in vivo resulting from the activity of specific ATRA hydroxylases, CYP26 enzymes,
      induced by ATRA in liver and target tissues. For this reason retinoic acid
      metabolism blocking agents (RAMBAs) have been developed for treating cancer and a
      wide range of other diseases. The synthesis, CYP26A1 inhibitory activity and
      molecular modeling studies of novel methyl 3-[4-(arylamino)phenyl]-3-(azole)-2,2
      dimethylpropanoates are presented. From this series of compounds clear SAR can be
      derived for 4-substitution of the phenyl ring with electron-donating groups more
      favourable for inhibitory activity. Both the methylenedioxyphenyl imidazole (17,
      IC(50) = 8 nM) and triazole (18, IC(50) = 6.7 nM) derivatives were potent
      inhibitors with additional binding interactions between the methylenedioxy moiety
      and the CYP26 active site likely to be the main factor. The 6-bromo-3-pyridine
      imidazole 15 (IC(50) = 5.7 nM) was the most active from this series compared with
      the standards liarozole (IC(50) = 540 nM) and R116010 (IC(50) = 10 nM).

PMID- 22989910
TI  - Characterization, bioinformatic analysis and dithiocarbamate inhibition studies
      of two new alpha-carbonic anhydrases, CAH1 and CAH2, from the fruit fly
      Drosophila melanogaster.
AB  - Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there
      are no articles on characterization of Drosophila melanogaster alpha-CAs. Data
      from invertebrate CA studies may provide opportunities for anti-parasitic drug
      development because alpha-CAs are found in many parasite or parasite vector
      invertebrates. We have expressed and purified D. melanogaster CAH1 and CAH2 as
      proteins of molecular weights 30kDa and 28kDa. CAH1 is cytoplasmic whereas CAH2
      is a membrane-attached protein. Both are highly active enzymes for the CO2
      hydration reaction, being efficiently inhibited by acetazolamide. CAH2 in the eye
      of D. melanogaster may provide a new animal model for CA-related eye diseases. A
      series of dithiocarbamates were also screened as inhibitors of these enzymes,
      with some representatives showing inhibition in the low nanomolar range.

PMID- 22989912
TI  - Novel amide- and sulfonamide-based aromatic ethanolamines: effects of various
      substituents on the inhibition of acid and neutral ceramidases.
AB  - In the present study we describe the design and synthesis of a series of amide-
      and sulfonamide-based compounds as inhibitor of recombinant acid and neutral
      ceramidases. Inhibition of ceramidases has been shown to induce apoptosis and to
      increase the efficacy of conventional chemotherapy in several cancer models. B
      13, lead in vitro inhibitor of acid ceramidase has been recently shown to be
      virtually inactive towards lysosomal acid ceramidase in living cells at lower
      concentrations and for a shorter time of treatment, suggesting the development of
      more potent inhibitors. In this study, a detailed SAR investigation has been
      performed to understand the effect of different substituents on the phenyl ring
      of amide- and sulfonamide-based compounds that partially resemble the structure
      of well-known inhibitors such as B-13, D-e-MAPP as well as NOE. Our results
      suggest that the electronic effects of the substituents on phenyl ring in B-13
      and D-e-MAPP analogues have negligible effects either in enhancing the inhibition
      potencies or for selectivity towards aCDase over nCDase. However, the
      hydrophobicity and the steric effects of longer alkyl chains (n-Pr, n-Bu or t-Bu
      groups) at the phenyl ring were found to be important for an enhanced selectivity
      towards aCDase over nCDase.

PMID- 22989913
TI  - Curcumin is an inhibitor of calcium/calmodulin dependent protein kinase II.
AB  - Calcium/calmodulin dependent protein kinase II (CaMKII) is involved in the
      mechanisms underlying higher order brain functions such as learning and memory.
      CaMKII participates in pathological glutamate signaling also, since it is
      activated by calcium influx through the N-methyl-d-aspartate type glutamate
      receptor (NMDAR). In our attempt to identify phytomodulators of CaMKII, we
      observed that curcumin, a constituent of turmeric and its analogs inhibit the
      Ca(2+)-dependent and independent kinase activities of CaMKII. We further report
      that a heterocyclic analog of curcumin I, (3,5-bis[beta-(4-hydroxy-3
      methoxyphenyl)ethenyl]pyrazole), named as pyrazole-curcumin, is a more potent
      inhibitor of CaMKII than curcumin. Microwave assisted, rapid synthesis of
      curcumin I and its heterocyclic analogues is also reported.

PMID- 22989914
TI  - Bruton's tyrosine kinase: oncotarget in myeloma.
AB  - Our findings therefore provide a strong rationale for investigating Btk
      inhibitors in MM and WM to target both tumor cells and their supporting BM
      microenvironment and thereby both suppress tumor cell growth and abrogate MM
      induced bone disease.

PMID- 22989915
TI  - The metal-insulator transition in nanocrystalline Pr0.67Ca0.33MnO3: the
      correlation between supercooling and kinetic arrest.
AB  - The transition and hysteresis widths of a disorder broadened first order magnetic
      transition vary in H-T space which influences the co-existing phase fraction at
      low temperature arising due to kinetic arrest of the first order transition. We
      explored the role of change in the relative width of the
      supercooling/superheating band and kinetic arrest band for a ferromagnetic
      metallic to antiferromagnetic insulating transition. It is shown that for a
      correlated kinetic arrest and supercooling bands, the topology of the
      devitrification curves (or transformation across the (H(K),T(K)) band during
      warming) changes with the change in the relative width of these two bands. In
      addition to this, for a broader kinetic arrest band, the transformation
      temperature across the superheating band under constant H now depends on the
      arrested phase fraction. These predictions have been tested on nanocrystalline
      Pr(0.67)Ca(0.33)MnO(3), which is known to show a large variation in hysteresis
      width in H-T space. This is the first report where correlation between the
      kinetic arrest band and the supercooling band has been shown experimentally, in
      contrast to the universal observation of anticorrelation reported so far.

PMID- 22989916
TI  - Distinctions in burst spiking between thalamic reticular nucleus cells projecting
      to the dorsal lateral geniculate and lateral posterior nuclei in the anesthetized
      rat.
AB  - Thalamic cell activity is under a significant influence of inhibition from the
      thalamic reticular nucleus (TRN) that is composed of domains connected with first
      and higher order thalamic nuclei, which are thought to subserve transmission of
      sensory inputs to the cortex and cortico-thalamo-cortical transmission of
      cortical outputs, respectively. Provided that TRN cells have distinct activities
      along with their projections to first and higher order thalamic nuclei, TRN cells
      could shape cell activities of the two thalamic nuclei in different manners for
      the distinct functions. In anesthetized rats, visual response and spontaneous
      activity were recorded from TRN cells projecting to the dorsal lateral geniculate
      (first order) and lateral posterior (higher order) nuclei (TRN-DLG and TRN-LP
      cells), using juxta-cellular recording and labeling techniques. TRN-DLG cells had
      a higher propensity for burst spiking and exhibited bursts of larger numbers of
      spikes with shorter inter-spike intervals as compared to TRN-LP cells in both
      visual response and spontaneous activity. Sustained effects of visual input on
      burst spiking were recognized in recurrent activation of TRN-DLG but not of TRN
      LP cells. Further, the features of burst spiking were related with the locations
      of topographically connected cell bodies and terminal fields. The difference in
      burst spiking contrasts with the difference between thalamic cells in the DLG and
      LP, which show low and high levels of burst spiking, respectively. The synergy
      between thalamic and TRN cell activities with their contrasting features of burst
      spiking may compose distinctive sensory processing and attentional gating
      functions of geniculate and extra-geniculate systems.

PMID- 22989917
TI  - In vivo voltage-dependent influences on summation of synaptic potentials in
      neurons of the lateral nucleus of the amygdala.
AB  - The amygdala has a fundamental role in driving affective behaviors in response to
      sensory cues. To accomplish this, neurons of the lateral nucleus (LAT) must
      integrate a large number of synaptic inputs. A wide range of factors influence
      synaptic integration, including membrane potential, voltage-gated ion channels
      and GABAergic inhibition. However, little is known about how these factors
      modulate integration of synaptic inputs in LAT neurons in vivo. The purpose of
      this study was to determine the voltage-dependent factors that modify in vivo
      integration of synaptic inputs in the soma of LAT neurons. In vivo intracellular
      recordings from anesthetized rats were used to measure post-synaptic potentials
      (PSPs) and clusters of PSPs across a range of membrane potentials. These studies
      found that the relationship between membrane potential and PSP clusters was
      sublinear, due to a reduction of cluster amplitude and area at depolarized
      membrane potentials. In combination with intracellular delivery of
      pharmacological agents, it was found that the voltage-dependent suppression of
      PSP clusters was sensitive to tetraethylammonium (TEA), but not cesium or a
      blocker of fast GABAergic inhibition. These findings indicate that integration of
      PSPs in LAT neurons in vivo is strongly modified by somatic membrane potential,
      likely through voltage-dependent TEA-sensitive potassium channels. Conditions
      that lead to a shift in membrane potential, or a modulation of the number or
      function of these ion channels will lead to a more uniform capacity for
      integration across voltages, and perhaps greatly facilitate amygdala-dependent
      behaviors.

PMID- 22989918
TI  - Ageing alters behavioural function and brain arginine metabolism in male Sprague
      Dawley rats.
AB  - A growing body of evidence suggests the involvement of L-arginine and its
      metabolites in the ageing and neurodegenerative processes. The present study
      assessed behavioural performance in 4- (young), 12- (middle-aged) and 24- (aged)
      month-old male Sprague-Dawley rats, and investigated age-related changes in the
      activity of two key arginine metabolic enzymes, nitric oxide synthase (NOS) and
      arginase, and the levels of L-arginine and its downstream metabolites in a number
      of memory-related brain structures. Aged rats were less anxious and performed
      poorly in the water maze task relative to the young and middle-aged rats, and
      both middle-aged and aged rats displayed reduced exploratory activity relative to
      the young ones. There were significant age-related changes in NOS and arginase
      activities, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine,
      putrescine, spermidine, spermine and glutamate, but not gamma-aminobutyric acid,
      in the CA1, CA2/3 and dentate gyrus sub-regions of the hippocampus and the
      prefrontal, entorhinal, perirhinal, postrhinal and temporal (an auditory cortex)
      cortices in a region-specific manner. Cluster analyses revealed that the nine
      related neurochemical variables formed distinct groups, which changed as a
      function of ageing. Multiple regression analyses revealed a number of significant
      correlations between the neurochemical and behavioural variables. The present
      study further supports the involvement of arginine metabolism in the ageing
      process, and provides further evidence of the effects of animals' behavioural
      experience on arginine metabolism.

PMID- 22989920
TI  - Inhibitory inputs to four types of spinocerebellar tract neurons in the cat
      spinal cord.
AB  - Spinocerebellar tract neurons are inhibited by various sources of input via
      pathways activated by descending tracts as well as peripheral afferents.
      Inhibition may be used to modulate transmission of excitatory information
      forwarded to the cerebellum. However it may also provide information on the
      degree of inhibition of motoneurons and on the operation of inhibitory premotor
      neurons. Our aim was to extend previous comparisons of morphological substrates
      of excitation of spinocerebellar neurons to inhibitory input. Contacts formed by
      inhibitory axon terminals were characterised as either GABAergic, glycinergic or
      both GABAergic/glycinergic by using antibodies against vesicular GABA
      transporter, glutamic acid decarboxylase and gephyrin. Quantitative analysis
      revealed the presence of much higher proportions of inhibitory contacts when
      compared with excitatory contacts on spinal border (SB) neurons. However similar
      proportions of inhibitory and excitatory contacts were associated with ventral
      spinocerebellar tract (VSCT) and dorsal spinocerebellar tract neurons located in
      Clarke's column (ccDSCT) and the dorsal horn (dhDSCT). In all of the cells, the
      majority of inhibitory terminals were glycinergic. The density of contacts was
      higher on somata and proximal versus distal dendrites of SB and VSCT neurons but
      more evenly distributed in ccDSCT and dhDSCT neurons. Variations in the density
      and distribution of inhibitory contacts found in this study may reflect
      differences in information on inhibitory processes forwarded by subtypes of
      spinocerebellar tract neurons to the cerebellum.

PMID- 22989919
TI  - Estrous cycle variations in GABA(A) receptor phosphorylation enable rapid
      modulation by anabolic androgenic steroids in the medial preoptic area.
AB  - Anabolic androgenic steroids (AAS), synthetic testosterone derivatives that are
      used for ergogenic purposes, alter neurotransmission and behaviors mediated by
      GABA(A) receptors. Some of these effects may reflect direct and rapid action of
      these synthetic steroids at the receptor. The ability of other natural allosteric
      steroid modulators to alter GABA(A) receptor-mediated currents is dependent upon
      the phosphorylation state of the receptor complex. Here we show that
      phosphorylation of the GABA(A) receptor complex immunoprecipitated by
      beta(2)/beta(3) subunit-specific antibodies from the medial preoptic area (mPOA)
      of the mouse varies across the estrous cycle; with levels being significantly
      lower in estrus. Acute exposure to the AAS, 17alpha-methyltestosterone (17alpha
      MeT), had no effect on the amplitude or kinetics of inhibitory postsynaptic
      currents in the mPOA of estrous mice when phosphorylation was low, but increased
      the amplitude of these currents from mice in diestrus, when it was high.
      Inclusion of the protein kinase C (PKC) inhibitor, calphostin, in the recording
      pipette eliminated the ability of 17alpha-MeT to enhance currents from diestrous
      animals, suggesting that PKC-receptor phosphorylation is critical for the
      allosteric modulation elicited by AAS during this phase. In addition, a single
      injection of 17alpha-MeT was found to impair an mPOA-mediated behavior (nest
      building) in diestrus, but not in estrus. PKC is known to target specific serine
      residues in the beta(3) subunit of the GABA(A) receptor. Although phosphorylation
      of these beta(3) serine residues showed a similar profile across the cycle, as
      did phosphoserine in mPOA lysates immunoprecipitated with beta2/beta3 antibody
      (lower in estrus than in diestrus or proestrus), the differences were not
      significant. These data suggest that the phosphorylation state of the receptor
      complex regulates both the ability of AAS to modulate receptor function in the
      mPOA and the expression of a simple mPOA-dependent behavior through a PKC
      dependent mechanism that involves the beta(3) subunit and other sites within the
      GABA(A) receptor complex.

PMID- 22989921
TI  - Duration of untreated negative and positive symptoms of psychosis and cognitive
      impairment in first episode psychosis.
AB  - BACKGROUND: Duration of untreated psychosis (DUP) has been significantly
      associated with poor clinical and social outcomes in First Episode Psychosis
      (FEP) patients, but an association with cognitive outcomes has not been clearly
      established. METHOD: Seventy-seven consecutively admitted, drug-naive patients
      with FEP were assessed at baseline and at 1month and 6months. Underlying
      dimensions of DUP (general prodrome and positive, negative and disorganisation
      symptoms) were assessed using the Symptom Onset in Schizophrenia (SOS) inventory
      (Perkins et al., 2000). To assess the effect of DUP on the neuropsychological
      status of the patients, a linear mixed-effect model was fitted to each
      neuropsychological dimension. These models included a dichotomised version of DUP
      (short versus long duration) as a fixed effect, several adjusting variables to
      account for patient differences, and a random effect to incorporate the
      longitudinal structure of the data. RESULTS: Patients with a short duration of
      untreated negative symptoms (DUNS) or a short duration of untreated positive
      symptoms (DUPS) outperformed patients with a long duration of untreated symptoms
      on memory tasks and a pre-attentional visual task but not on measures of verbal
      fluency, attention, reaction time, visual processing and executive functions.
      CONCLUSIONS: This study provides additional support for an early intervention to
      shorten DUP to facilitate a better outcome in memory and attentional domains of
      FEP patients.

PMID- 22989922
TI  - [The long haul to achieve the objectives in the treatment of dyslipidaemias].

PMID- 22989923
TI  - Cell surface properties and fatty acids composition of Stenotrophomonas
      maltophilia under the influence of hydrophobic compounds and surfactants.
AB  - Surface properties of newly isolated Stenotrophomonas maltophilia strain 6 were
      tested. The bacteria were stored in two different ways to determine the influence
      of hydrocarbons and surfactants on surface and enzymatic characteristics of the
      isolated strain. The influence of surface active agents, natural and synthetic,
      on membrane's lipid composition and cell surface hydrophobicity (CSH) was
      investigated. Our results indicate that long-term contact with diesel oil as a
      hydrophobic sole carbon source leads to the increased enzymatic activity of S.
      maltophilia strain 6 as well as to modification of fatty acids profiles and its
      facility to adhere to hydrophobic compounds. Among surfactants there were
      saponins and Triton X-100 which changed the composition of fatty acids the most,
      increasing the amount of branched acids. The comparison of fatty acid profiles
      with CSH of systems with diesel oil, rhamnolipids, saponins and Triton X-100
      points out that the growing amount of hydroxy fatty acids corresponds to lower
      hydrophobicity. Moreover, CSH is a dynamic parameter which can change during
      cultivation of microorganisms.

PMID- 22989924
TI  - Production of 2,3-butanediol by a low-acid producing Klebsiella oxytoca NBRF4.
AB  - 2,3-Butanediol (2,3-BDO) is a value-added chemical with great potential for the
      industrial production of synthetic rubber, plastic and solvent. For microbial
      production of 2,3-BDO, in this study, Klebsiella oxytoca NBRF4 was constructed by
      chemical mutation and screening against NaBr, NaBrO(3) and fluoroacetate. Among
      metabolic enzymes involved in the production of lactate, acetate and 2,3-BDO, K.
      oxytoca NBRF4 possessed 1.2 times lower specific activities of lactate
      dehydrogenase and phosphotransacetylase, and 22% higher specific acetoin
      reductase activity than the K. oxytoca ATCC43863 control strain. A series of
      batch fermentations in a defined medium and application of a statistical tool of
      response surface method led to the determination of optimal culture conditions:
      10% dissolved oxygen level, pH 4.3 and 38 degrees C. The actual results of batch
      fermentation at the optimal conditions using 44 g/L glucose were coincident with
      the predetermined values: 14.4 g/L 2,3-BDO concentration, 0.32 g/g yield. To
      increase 2,3-BDO titer, fed-batch fermentation of K. oxytoca NBRF4 was performed
      by an intermittent feeding of 800 g/L glucose to control its concentration around
      5-20 g/L in the culture broth. Finally, 34.2g/L 2,3-BDO concentration and 0.35
      g/g yield were obtained without organic acid production in 70 hours of the fed
      batch culture, which were 2.4 and 1.2 times higher than those of the batch
      fermentation using 44 g/L glucose.

PMID- 22989925
TI  - Aneurysm identification by analysis of the blood-vessel skeleton.
AB  - At least 1% of the general population have an aneurysm (or possibly more) in
      their cerebral blood vessels. If an aneurysm ruptures, it kills the patient in up
      to 60% of cases. In order to choose the optimal treatment, clinicians have to
      monitor the development of the aneurysm in time. Nowadays, aneurysms are
      typically identified manually, which means that the monitoring is often imprecise
      since the identification is observer dependent. As a result, the number of
      misdiagnosed cases may be large. This paper proposes a fast semi-automatic method
      for the identification of aneurysms which is based on the analysis of the
      skeleton of blood vessels. Provided that the skeleton is accurate, the results
      achieved by our method have been deemed acceptable by expert clinicians.

PMID- 22989926
TI  - Plasmablastic lymphoma of the larynx: report of two cases.
AB  - OBJECTIVE: To report two cases of laryngeal plasmablastic lymphoma, a rare and
      relatively recently described form of non-Hodgkin's lymphoma. It has not
      previously been described in the larynx, nor associated with upper airway
      obstruction. CASE REPORTS: We describe the clinicopathological features of two
      such cases in human immunodeficiency virus positive patients, and we discuss
      their unusual presentations and diagnostic features. CONCLUSION: When evaluating
      a laryngeal tumour, plasmablastic lymphoma and other non-Hodgkin's lymphomata
      should be considered as differential diagnoses, particularly in the setting of a
      high prevalence of human immunodeficiency virus infection. Biopsy with detailed
      histopathological and immunohistochemical evaluation is recommended to ensure
      correct diagnosis and optimal management.

PMID- 22989927
TI  - Kinetics of human cytomegalovirus (HCMV) DNAemia in transplanted patients
      expressed in international units as determined with the Abbott RealTime CMV assay
      and an in-house assay.
AB  - BACKGROUND: Consensus human cytomegalovirus (HCMV) DNA cut-off values for
      preemptive therapy in transplant recipients have not yet been defined, mainly due
      to the lack of real-time PCR standardization. OBJECTIVES: (i) To compare the
      kinetics of HCMV DNA in transplanted patients using an in-house real-time PCR
      assay (Pavia assay) and the new Abbott RealTime CMV assay; (ii) to verify assay
      concordance in the identification of patients eligible for preemptive treatment
      and (iii) standardize results with international units (IUs) using the WHO
      International HCMV DNA Standard as a reference. STUDY DESIGN: The kinetics of
      HCMV disseminated infection was retrospectively evaluated in 513 stored whole
      blood samples from 37 transplanted patients enrolled in randomized prospective
      studies designed for the clinical validation of HCMV DNA cut-off values.
      Conversion factors of HCMV DNA copy number to WHO international units (IUs) were
      determined. RESULTS: Among the 513 samples, 352 (68.6%) were concordant positive,
      42 (8.1%) concordant negative and 119 (23.1%) discordant. All discordant samples
      resulted positive by the Abbott RealTime CMV assay and negative by the Pavia
      assay, showing higher sensitivity for the Abbott RealTime CMV assay. A
      significant correlation was observed between concordant positive samples
      (r=0.89). HCMV DNAemia determined by each assay showed overlapping kinetics.
      Expression of results as IU/ml provided the best results in preemptive treatment
      simulation. CONCLUSION: HCMV DNAemia cut-off values determined using our in-house
      assay and expressed as IU/ml appear valid for use in commercial assays as well as
      other potential in-house assays.

PMID- 22989928
TI  - Vector-based phase classification of initial dips during word listening using
      near-infrared spectroscopy.
AB  - This study examined the classification of initial dips during passive listening
      to single words by analysis of vectors of deoxyHb and oxyHb measurements
      simultaneously derived from near-infrared spectroscopy. The initial dip response
      during a single-word 1.5-s task in 13 healthy participants was significant only
      in the language area, which includes the left posterior superior temporal gyrus
      and angular gyrus. Event-related vectors of responses to comprehended words moved
      significantly into phase 4, a dip phase, whereas vectors of responses to unknown
      words moved into a nondip phase (P<0.05). The same results were reproduced after
      previously unknown words were learnt by the participants. Among the five dip
      phases, reflecting variations in transient oxygen metabolic regulation during a
      task, the frequency of occurrence of hypoxic-ischemic initial dips (decreased
      oxyHb) was around three times that of the canonical dip (increased deoxyHb and
      oxyHb). Phase classification of event-related vectors enhances the slight amount
      of oxygen exchange that occurs in word recognition, which has been difficult to
      detect because of its small amplitude.

PMID- 22989929
TI  - Expression of P16 cell cycle inhibitor in human cord blood CD34+ expanded cells
      following co-culture with bone marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: Because of insufficient number of cord blood hematopoietic stem cells
      (CB-HSC), expansion of these cells seems to be important for clinical application
      in adults. Cell cycle inhibitors are important regulators in normal hematopoietic
      regeneration. In this study,  mRNA expression and promoter methylation status of
      p16 were evaluated during CB-HSC ex vivo expansion using cytokines and a co
      culture system with mesenchymal stem cells (MSCs) feeder layer. METHODS: ex vivo
      cultures of CB-HSCs were performed in three culture  conditions for 14 days:
      cytokines with MSCs feeder layer, cytokines without MSCs feeder layer, and co
      culture with MSCs without cytokine. After expansion, measuring total number of
      cells, CD34+ cells and colony-forming unit (CFU) assay was performed. Methylation
      status of the p16(INK4a)  gene promoter was analyzed using methylation-specific
      polymerase chain reaction (PCR), and p16 mRNA expression was evaluated by real
      time reverse transcriptase-PCR. RESULTS: Maximum CB-HSC expansion was observed in
      day 10 of expansion. The data showed that after 10 days,  p16 mRNA expression in
      the expanded cells at the co-culture system without cytokine was higher than in
      CD34+ fresh cells (P < 0.01); however, p16 mRNA expression in the expanded cells
      at both cytokine cultures with and without MSCs feeder layer was decreased. p16
      gene promoter  of expanded CD34+ cells remained in unmethylated form just like
      fresh CD34+ cells in all the three culture conditions at days 5, 10, and 14 of
      culture. CONCLUSION: Expression in HSCs of p16(INK4a), an important cell cycle
      regulator in normal hematopoietic regeneration  disruption of which is involved
      in leukemic cell development, was increased during 10 days of expansion in co
      culture with MSCs feeder layers. Also, no methylation of p16 promoter was
      observed, which is capable of initiating some leukemic cell progression or
      disruption in hematopoietic regeneration.

PMID- 22989930
TI  - Rats (Rattus norvegicus) and pigeons (Columbia livia) are sensitive to the
      distance to food, but only rats request more food when distance increases.
AB  - Three experiments investigated foraging by rats and pigeons. In Experiment 1,
      each response on a manipulandum delivered food to a cup, with the distance
      between the manipulandum and the cup varying across conditions. The number of
      responses made before traveling to collect and eat the food increased with
      distance for rats, but not for pigeons. In Experiment 2, two manipulanda were
      placed at different distances from a fixed food source; both pigeons and rats
      preferentially used the manipulandum closest to the food source. Experiment 3 was
      a systematic replication of Experiment 1 with pigeons. In different conditions,
      each peck on the left key increased the upcoming hopper duration by 0.5, 1.5 or
      2.5s. Completing a ratio requirement on the right key of 1, 4, 8, 16 or 32 pecks,
      depending on the condition, then produced the food hopper for a duration that
      depended on the number of prior left pecks. As the ratio requirement increased on
      the right key, pigeons responded more on the left key and earned more food.
      Overall, the results replicate previous research, underlining similarities and
      differences between these species. The results are discussed in terms of optimal
      foraging, reinforcer sensitivity and delay discounting.

PMID- 22989931
TI  - Tumour promoting functions of TGF-beta in CML-initiating cells.
AB  - Recent data have shown that transforming growth factor-beta (TGF-beta) plays bi
      directional roles in the maintenance of cancer stem cells in a cell-type and
      context-dependent manner. Zhu et al. (TGF-beta1-induced PI3K/Akt/NF-kappaB/MMP9
      signalling pathway is activated in Philadelphia chromosome-positive chronic
      myeloid leukaemia hemangioblasts. J. Biochem. 2011;149:405-414) studied the
      functions of TGF-beta in hemangioblasts from patients with chronic myeloid
      leukemia (CML), which displayed properties of leukemia-initiating cells. They
      have shown that the BCR/ABL oncoprotein induced the production of TGF-beta in the
      CML hemangioblasts, and that TGF-beta activated the phosphoinositide 3-kinase-Akt
      NF-kappaB pathway in these cells. Activation of this pathway enhanced the
      production of matrix metalloproteinase-9 leading to increased synthesis of
      soluble Kit ligand and intercellular adhesion molecule-1. TGF-beta is known to
      maintain the CML-initiating cells through the Akt-FoxO pathway. Together, these
      findings suggest that TGF-beta may exhibit multiple functions in progression of
      CML through acting on leukemia-initiating cells.

PMID- 22989932
TI  - Isolation of antibody V(D)J sequences from single cell sorted rhesus macaque B
      cells.
AB  - Studies in nonhuman primates offer information of high relevance to clinical
      medicine due to their close genetic relationship with humans. Here, we
      established an optimized protocol for the isolation of antibody V(D)J sequences
      from rhesus macaque B cells. Nested PCR primers were designed to align to
      sequences flanking the V(D)J coding region to enable amplification of highly
      mutated antibody sequences. The primers were evaluated using cDNA from bulk PBMCs
      as well as from single-sorted memory and naive B cells from several macaques to
      ascertain effective germline coverage. The nested PCR efficiency reached 60.6%
      positive wells for heavy chain amplification, 39.2% for kappa chain, and 23.7%
      for lambda chain sequences. Matching heavy and light chain sequences, indicating
      antibodies that potentially can be cloned, were obtained in 50% of the positive
      wells. Using these primers, we found that the efficiency and specificity of V(D)J
      amplifications were markedly improved compared to when primers designed for human
      Ab isolation were used. In particular, the amplification of recombined light
      chain VJ sequences was improved. Thus, we describe the design and testing of a
      new set of rhesus-specific primers that enable efficient and specific
      amplification of heavy, kappa and lambda V(D)J genes from single sorted B cells.
      The use of these primers will facilitate future efforts to clone and express
      rhesus macaque MAbs for genetic, functional and structural analyses.

PMID- 22989933
TI  - Attentional bias towards pain-related information diminishes the efficacy of
      distraction.
AB  - Distraction is a strategy that is commonly used to cope with pain. Results
      concerning the efficacy of distraction from both experimental and clinical
      studies are variable, however, and indicate that its efficacy may depend on
      particular circumstances. Several models propose that distraction may be less
      effective for people who display a large attentional bias towards pain-related
      information. This hypothesis was tested in an experimental context with 53 pain
      free volunteers. First, attentional bias towards cues signalling the occurrence
      of pain (electrocutaneous stimuli) and towards words describing the sensory
      experience of this painful stimulus was independently assessed by means of 2
      behavioural paradigms (respectively, spatial cueing task and dot-probe task).
      This was followed by a subsequent distraction task during which the efficacy of
      distraction, by directing attention away from the electrocutaneous stimuli, was
      tested. In addition, state-trait anxiety, catastrophic thinking, and initial pain
      intensity were measured. Results indicated that people who display a large
      attentional bias towards predictive cues of pain or who initially experience the
      pain as more painful benefit less from distraction on a subsequent test. No
      effects were found between attentional bias towards pain words, state-trait
      anxiety, catastrophic thinking, and the efficacy of distraction. Current findings
      suggest that distraction should not be used as a 'one size fits all' method to
      control pain, but only under more specific conditions.

PMID- 22989934
TI  - Second primary malignancies and myeloma therapy: fad or fact?
AB  - The risk adaptive therapy approach within low risk patients may involve limiting
      post-transplant IMiD exposure in patients who have a higher potential for SPM
      development. It may well be that we are looking at the tip of the iceberg in the
      year 2012 and SPMs may emerge as an important long-term sequela with further
      follow-up.

PMID- 22989936
TI  - Management of chronic venous disease by primary care.
AB  - OBJECTIVE: To assess the patterns of referral for chronic venous disease (CVD).
      METHOD: General practitioners (GPs) were invited by an email to complete a
      validated online survey evaluating the referral and community management of CVD.
      RESULTS: A total of 138 participants were recruited. Most GPs (85%) saw fewer
      than 50 patients with CVD a year. Thirty-one percent were aware of National
      Institute for Clinical Excellence referral guidelines for CVD and 36% were aware
      of and agreed with local referral guidelines. Eleven percent were aware of
      clinical venous scoring systems. Sixty-three percent believed mild CVD would
      progress and 84% believed treatment would improve the quality of life. Sixteen
      referred C3 disease, 43% C4, 37% C5 and 65% C6 disease. Forty-one percent would
      refer on request. Pain symptoms increased referral in C2 disease. Endothermal
      ablation was believed available to 33% and traditional stripping to 62% and 27%
      were unaware of the treatment options. Forty-five percent were happy to provide
      postoperative care. CONCLUSIONS: Despite national guidelines, the management of
      CVD in the UK is variable.

PMID- 22989937
TI  - 'C' class in conflict between clinics and duplex.

PMID- 22989938
TI  - Left phrenic nerve injury after cryoballoon ablation of the pulmonary veins.

PMID- 22989939
TI  - Poor health status and distress in cardiac patients: the role of device therapy
      vs. underlying heart disease.
AB  - AIMS: Implantable cardioverter defibrillator (ICD) therapy, which includes the
      risk of shocks, is considered the primary culprit of reductions in patient
      reported outcomes (PROs; e.g. health status and distress), thereby negating the
      role of underlying disease severity. We examined the relative influence of living
      with an ICD vs. congestive heart failure (CHF) on PROs and compared (i) ICD
      patients without CHF (ICD only), (ii) CHF patients without an ICD (CHF-only), and
      (iii) CHF patients with an ICD (ICD + CHF). METHODS AND RESULTS: Separate cohorts
      of ICD and CHF patients (N = 435; 75% men) completed PROs at baseline, 6 and 12
      months. Groups differed on physical health status only at baseline (F((2,415)) =
      7.15, P = 0.001) and on anxiety at 12 months (F((2,415)) = 4.04, P = 0.01); ICD +
      CHF patients had the most impaired physical health status but the lowest anxiety
      level followed by the ICD only and CHF only patients. Congestive heart failure
      only patients had the most impaired mental health status and reported the highest
      level of anxiety as compared to the ICD only (P < 0.001) and ICD + CHF groups (P
      = 0.009), while the two latter groups did not differ. The effect sizes ranged
      from very small (0.03) to moderate-large (0.69). Groups did not differ in
      depression scores. CONCLUSION: Congestive heart failure patients reported worse
      PROs as compared to ICD patients, although the magnitude of the differences was
      relatively small. This suggests that the well being of patients is not
      necessarily negatively influenced by the implantation of an ICD, and that
      underlying heart disease may have at least an equal if not greater influence on
      PROs.

PMID- 22989940
TI  - Differential serum cytokine responses to inactivated and live attenuated seasonal
      influenza vaccines.
AB  - Despite vaccine efforts, influenza outbreaks pose a significant threat to global
      public health. There are two commercially available seasonal influenza vaccines
      in the United States: the trivalent inactivated vaccine (TIV), delivered
      parenterally, and the live attenuated influenza vaccine (LAIV), delivered
      intranasally. Although both vaccines are generally efficacious, the immunologic
      mechanisms which contribute to protective immunity are incompletely understood.
      Thus, we investigated the protracted effects of TIV and LAIV on serum cytokine
      profiles at 14 and 28 days post-vaccination (when antibody titers are peak) in
      healthy adults over two influenza seasons. Vaccination with TIV was associated
      with a small, yet significant, decrease in the levels of both IL-8 and TNF-alpha
      at 14 and 28 days post-vaccination. LAIV, however, had no impact on serum
      cytokine levels. Similarly, analysis of serum antibody titers indicated that TIV
      recipients had a significantly higher sero-response rate compared to LAIV
      recipients, as has been previously shown. Finally, we examined the relationship
      between baseline serum cytokine levels and antibody responses to TIV (LAIV
      recipients were excluded due to the poor sero-response rate). Interestingly, in
      TIV recipients pre-vaccination levels of IL-8 were higher in sero-responders
      compared to non-responders. Collectively, these data suggest that cytokines may
      influence vaccine outcomes and indicate that parenteral immunization with TIV
      induces a sustained, systemic cytokine response which lasts for weeks.

PMID- 22989941
TI  - Nano-ice models for the water aggregates observed on the h-BN/Rh(111) nanomesh.
AB  - When a large amount of water is deposited onto a bare h-BN/Rh(111) nanomesh, the
      formation of ordered and stable nano-ice crystals in the pores has been
      experimentally observed. The present work proposes different possible models for
      the structure of the observed clusters, based on density functional theory
      calculations of two-dimensional water lattices adsorbed on free-standing
      hexagonal BN. Through the investigation of the electronic properties, the
      interaction with BN, and the distribution of the molecular dipoles, the most
      probable two-dimensional arrangement has been identified. Finally, a model is
      proposed for the nano-ice cluster trapped in the pore of the nanomesh, which
      constitutes 38 molecules distributed according to the most probable two
      dimensional arrangement on free-standing BN. Structural and electronic properties
      of the optimized nano-ice cluster are also reported, and it is shown that the
      model is consistent with the experimental observation.

PMID- 22989942
TI  - Teaching acupuncture: the Brazilian Medical Residency Programme.
AB  - Acupuncture has had a successful story in Brazil. With its use in the public
      health system supported by legislation since 1988, its recognition as a medical
      specialty in 1995 enabled the introduction of an annual board examination and the
      creation of an official Medical Residency Programme. Since then, medical
      acupuncture has developed considerably, mostly through its massive spread into
      the Brazilian public health system. Brazil is the only country outside China that
      has created a Medical Residency Programme on Acupuncture. The 2-year programme
      consists of 5760 training hours, beginning with major clinical areas (internal
      medicine, neurology, orthopaedics and gynaecology) during 24 weeks in the first
      year. The residents study and practice acupuncture using the traditional Chinese
      Medicine approach and also the biomedical model. Specialists educated by this
      programme are therefore expected to have an optimum knowledge of both Western and
      Eastern medicine. Since it was first created, nine public health institutions
      have adopted the residency programme on acupuncture so, rather than being an
      alternative therapy, acupuncture has become an easily accessible and well
      accepted conventional medical resource in Brazil.

PMID- 22989943
TI  - Taste, olfactory and food texture reward processing in the brain and the control
      of appetite.
AB  - Complementary neuronal recordings and functional neuroimaging in human subjects
      show that the primary taste cortex in the anterior insula provides separate and
      combined representations of the taste, temperature and texture (including fat
      texture) of food in the mouth independently of hunger and thus of reward value
      and pleasantness. One synapse on, in the orbitofrontal cortex (OFC), these
      sensory inputs are for some neurons combined by learning with olfactory and
      visual inputs, and these neurons encode food reward in that they only respond to
      food when hungry, and in that activations correlate with subjective pleasantness.
      Cognitive factors, including word-level descriptions, and attention modulate the
      representation of the reward value of food in the OFC and a region to which it
      projects, the anterior cingulate cortex. Further, there are individual
      differences in the representation of the reward value of food in the OFC. It is
      argued that over-eating and obesity are related in many cases to an increased
      reward value of the sensory inputs produced by foods, and their modulation by
      cognition and attention that over-ride existing satiety signals. It is proposed
      that control of all rather than one or several of these factors that influence
      food reward and eating may be important in the prevention and treatment of
      overeating and obesity.

PMID- 22989945
TI  - Methyl jasmonate-induced lateral root formation in rice: the role of heme
      oxygenase and calcium.
AB  - Lateral roots (LRs) play important roles in increasing the absorptive capacity of
      roots as well as to anchor the plant in the soil. Therefore, understanding the
      regulation of LR development is of agronomic importance. In this study, we
      examined the effect of methyl jasmonate (MJ) on LR formation in rice. Treatment
      with MJ induced LR formation and heme oxygenase (HO) activity. As well, MJ could
      induce OsHO1 mRNA expression. Zinc protoporphyrin IX (the specific inhibitor of
      HO) and hemoglobin [the carbon monoxide/nitric oxide (NO) scavenger] reduced LR
      formation, HO activity and OsHO1 expression. LR formation and HO activity induced
      by MJ was reduced by the specific NO scavenger 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-oxide. The effects of Ca(2+) chelators, Ca(2+)
      channel inhibitors, and calmodulin (CaM) antagonists on LR formation induced by
      MJ were also examined. All these inhibitors were effective in reducing the action
      of MJ. However, Ca(2+) chelators and Ca(2+) channel inhibitors induced HO
      activity when combining with MJ further. It is concluded that Ca(2+) may regulate
      MJ action mainly through CaM-dependent mechanism.

PMID- 22989944
TI  - Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide
      gated channel currents?
AB  - ZD7288 has been widely used as a tool in the study of hyperpolarization-activated
      cyclic nucleotide-gated channels (HCN channels), and to test the relationships
      between HCN channels and heart and brain function. ZD7288 is widely considered a
      selective blocker of HCN currents. Here we show that ZD7288 inhibits not only HCN
      channel currents, but also Na(+) currents in DRG neurons and ZD7288 was confirmed
      to inhibit Na(+) current in HEK293 cells transfected with Na(v)1.4 plasmids. Thus
      our findings challenge the view that ZD7288 is a selective blocker of HCN
      channels. Conclusions about the role of NCN channels in neuronal function should
      be re-evaluated if based exclusively on the effect of ZD7288.

PMID- 22989946
TI  - Redox changes accompanying storage protein mobilization in moist chilled and warm
      incubated walnut kernels prior to germination.
AB  - Alterations in the redox state of storage proteins and the associated proteolytic
      processes were investigated in moist-chilled and warm-incubated walnut (Juglans
      regia L.) kernels prior to germination. The kernel total protein labeling with a
      thiol-specific fluorochrome i.e. monobromobimane (mBBr) revealed more reduction
      of 29-32 kDa putative glutelins, while in the soluble proteins, both putative
      glutelins and 41, 55 and 58 kDa globulins contained reduced disulfide bonds
      during mobilization. Thus, the in vivo more reduced disulfide bonds of storage
      proteins corresponds to greater solubility. After the in vitro reduction of
      walnut kernel proteins pre-treated by N-ethyl maleimide (NEM) with
      dithioerythrethiol (DTT) and bacterial thioredoxin, the 58 kDa putative globulin
      and a 6 kDa putative albumin were identified as disulfide proteins. Thioredoxin
      stimulated the reduction of the H(2)O(2)-oxidized 6 kDa polypeptide, but not the
      58 kDa polypeptide by DTT. The solubility of 6 kDa putative albumin, 58 and 19-24
      kDa putative globulins and glutelins, respectively, were increased by DTT. The in
      vitro specific mobilization of the 58 kDa polypeptide that occurred at pH 5.0 by
      the kernel endogenous protease was sensitive to the serine-protease inhibitor
      phenylmethylsulfonyl fluoride (PMSF) and stimulated by DTT. The specific
      degradation of the 58 kDa polypeptide might be achieved through thioredoxin
      mediated activation of a serine protease and/or reductive unfolding of its 58 kDa
      polypeptide substrate. As redox changes in storage proteins occurred equally in
      both moist chilled and warm incubated walnut kernels, the regulatory functions of
      thioredoxins in promoting seed germination may be due to other germination
      related processes.

PMID- 22989947
TI  - Fast topological imaging.
AB  - Mathematical optimization methods based on the topological sensitivity analysis
      have been used to develop innovative ultrasonic imaging methods. With a single
      illumination of the medium, they have proved experimentally to yield a lateral
      resolution comparable to classical multiple-illumination techniques. As these
      methods are based on the numerical simulations of two wave fields, they require
      extensive computation. A time-domain finite-difference scheme is usually used for
      that purpose. This paper presents the development of an experimental imaging
      method based on the topological sensitivity. The numerical cost is reduced by
      replacing the numerical simulations by simple mathematical operations between the
      radiation patterns of the array's transducers and the frequency-domain signals to
      be emitted. These radiation patterns are preliminary computed once and for all.
      They were obtained with a finite element model for the anisotropic elastodynamic
      case and with semi-analytical integrations for the acoustic case. Experimental
      results are presented for a composite material sample and for a prefractal
      network immersed in water. A lateral resolution below 2.5 times the wavelength is
      obtained with a single plane wave illumination. The method is also applied with
      multiple illuminations, so that objects hidden in complex media can be
      investigated.

PMID- 22989948
TI  - Study of stress-induced velocity variation in concrete under direct tensile force
      and monitoring of the damage level by using thermally-compensated Coda Wave
      Interferometry.
AB  - In this paper, we describe an experimental study of concrete behavior under a
      uniaxial tensile load by use of the thermally-compensated Coda Wave
      Interferometry (CWI) analysis. Under laboratory conditions, uniaxial tensile load
      cycles are imposed on a cylindrical concrete specimen, with continuous ultrasonic
      measurements being recorded within the scope of bias control protocols. A
      thermally-compensated CWI analysis of multiple scattering waves is performed in
      order to evaluate the stress-induced velocity variation. Concrete behavior under
      a tensile load can then be studied, along with CWI results from both its elastic
      performance (acoustoelasticity) and plastic performance (microcracking
      corresponding to the Kaiser effect). This work program includes a creep test with
      a sustained, high tensile load; the acoustoelastic coefficients are estimated
      before and after conducting the creep test and then used to demonstrate the
      effect of creep load.

PMID- 22989949
TI  - Mechanical characterization of sintered piezo-electric ceramic material using
      scanning acoustic microscope.
AB  - Lead Zirconate Titanate (PZT) is a piezo-electric ceramic material that needs to
      be characterized for its potential use in microelectronics. Energy dispersive X
      ray analysis (EDX) is conducted to determine the chemical composition of the PZT
      ceramics. The scanning electron microscope (SEM) is performed to study the
      surface morphology, grain structure and grain boundaries. The SEM image helps us
      to understand the surface wave propagation and scattering phenomena by the PZT
      and the reason for its anisotropy and inhomogeneity due to the grain structure.
      In this paper scanning acoustic microscopy at 100 MHz excitation frequency is
      conducted for determining mechanical properties of PZT. Earlier works reported
      only the longitudinal wave speed in PZT while in this paper longitudinal, shear
      and surface acoustic wave speeds of sintered PZT are measured from its acoustic
      material signature (AMS) curves, also known as V(z) curves. AMS or V(z) curve is
      the variation of the output voltage as a function of the distance between the
      acoustic lens focal point and the reflecting surface. The average velocities of
      longitudinal, shear and surface acoustic waves in a PZT specimen are determined
      from its V(z) curve generated at 100 MHz excitation frequency and found to be
      over 5000 m/s, over 3000 m/s and between 2500 and 3000 m/s, respectively. From
      these velocities all elastic constants of the specimen are obtained.

PMID- 22989950
TI  - Remission of positive symptoms according to the "remission in Schizophrenia
      Working Group" criteria: a longitudinal study of cognitive functioning.
AB  - Schizophrenia patients in positive symptomatic remission (PSR; n=39) were
      assessed using a longitudinal research design. The patients were found to exhibit
      widespread cognitive impairments that were stable over the three-year follow-up
      period. The findings support a generalized and stable cognitive impairment
      profile among schizophrenia patients in partial symptomatic remission.

PMID- 22989951
TI  - Towards uncertainty quantification and inference in the stochastic SIR epidemic
      model.
AB  - In this paper we address the problem of estimating the parameters of Markov jump
      processes modeling epidemics and introduce a novel method to conduct inference
      when data consists on partial observations in one of the state variables. We take
      the classical stochastic SIR model as a case study. Using the inverse-size
      expansion of van Kampen we obtain approximations for the first and second moments
      of the state variables. These approximate moments are in turn matched to the
      moments of an inputed Generic Discrete distribution aimed at generating an
      approximate likelihood that is valid both for low count or high count data. We
      conduct a full Bayesian inference using informative priors. Estimations and
      predictions are obtained both in a synthetic data scenario and in two Dengue
      fever case studies.

PMID- 22989953
TI  - Frequency of infection by Neospora caninum in wild rodents associated with dairy
      farms in Aguascalientes, Mexico.
AB  - The purpose of this study was to detect the presence of Neospora caninum in
      tissues from wild rodents associated with dairy farms in Aguascalientes, Mexico.
      Individuals from Mus musculus, Rattus novergicus and Spermophilus variegatus were
      caught in dairy farms with history of positive status to N. caninum. A total of
      33 rodents were caught from which samples were taken of brain, spinal cord, liver
      and heart and were tested with nested PCR and Immunohistochemistry (IHC). Results
      obtained with PCR showed that M. musculus had 77% (10/13) positive samples to N.
      caninum, S. variegatus had 71% (10/14) and R. novergicus had 50% (3/6). The
      results obtained with IHC showed that 15% (2/13) of M. musculus individuals were
      positive, while 43% (6/14) of S. variegatus and 33% (2/6) R. novergicus were also
      positive. This is the first report of the presence of N. caninum in S.
      variegatus.

PMID- 22989952
TI  - The bZIP repressor proteins, c-Jun dimerization protein 2 and activating
      transcription factor 3, recruit multiple HDAC members to the ATF3 promoter.
AB  - JDP2, is a basic leucine zipper (bZIP) protein displaying a high degree of
      homology with the stress inducible transcription factor, ATF3. Both proteins bind
      to cAMP and TPA response elements and repress transcription by multiple
      mechanisms. Histone deacetylases (HDACs) play a key role in gene inactivation by
      deacetylating lysine residues on histones. Here we describe the association of
      JDP2 and ATF3 with HDACs 1, 2-6 and 10. Association of HDAC3 and HDAC6 with JDP2
      and ATF3 occurs via direct protein-protein interactions. Only part of the N
      terminal bZIP motif of JDP2 and ATF3 basic domain is necessary and sufficient for
      the interaction with HDACs in a manner that is independent of coiled-coil
      dimerization. Class I HDACs associate with the bZIP repressors via the DAC
      conserved domain whereas the Class IIb HDAC6 associates through its C-terminal
      unique binder of ubiquitin Zn finger domain. Both JDP2 and ATF3 are known to bind
      and repress the ATF3 promoter. MEF cells treated with histone deacetylase
      inhibitor, trichostatin A (TSA) display enhanced ATF3 transcription. ATF3
      enhanced transcription is significantly reduced in MEF cells lacking both ATF3
      and JDP2. Collectively, we propose that the recruitment of multiple HDAC members
      to JDP2 and ATF3 is part of their transcription repression mechanism.

PMID- 22989954
TI  - Genetic characterisation of Toxoplasma gondii isolates from European beavers
      (Castor fiber) and European wildcats (Felis silvestris silvestris).
AB  - Six free-ranging European beavers (Castor fiber) from Berlin greater metropolitan
      area and twelve European wildcats (Felis silvestris silvestris) originating from
      the German Federal State of Saxony-Anhalt were found dead and their carcasses
      were submitted for necropsy. Brain and lung samples were analysed for the
      presence of Toxoplasma gondii DNA. Histo-pathologic analysis of one beaver
      revealed several cyst-like protozoal structures in parts of the brain. Tissue DNA
      isolated from all animal samples was analysed by a specific T. gondii-PCR. Two
      beavers and four wildcats tested T. gondii-positive. DNA of the parasites was
      further analysed by PCR-RFLP typing using nine markers (nSAG2, SAG3, BTUB, GRA6,
      c22-8, c29-2, L358, PK1 and Apico). Only T. gondii type II alleles were detected,
      except for the Apico locus, where type I alleles were observed in two isolates
      from beavers and in three from wild cats. The results of this study indicate that
      type II T. gondii (including type II variant strain) is the most common genotype
      infecting wildcats and beavers from Germany.

PMID- 22989955
TI  - Unusual location of BCR-ABL1 fusion sequences in a chronic myeloid leukemia
      patient.
AB  - We describe a case of a chronic myeloid leukemia patient displaying the chimeric
      BCR-ABL1 gene on 12p11. Chromosome analysis revealed complex chromosome
      aberration involving chromosomes 9, 12, and 22. Fluorescence in situ
      hybridization revealed an unusual signal pattern  revealing the BCR-ABL1 fusion
      signal on chromosome 12, while no reciprocal ABL1-BCR fusion was detected on
      der(9) chromosome. The relocation of BCR-ABL1 fusion sequences to 12p11 site in
      our patient represents a rare type of variant translocation, as in almost all
      patients  the chimeric BCR-ABL1 gene is located on der(22) chromosome. Our case
      illustrates the challenge of recognizing a complex pattern of cytogenetic
      aberrations that occur with variant t(9;22) and may add further information about
      clinical significance of unusual variant Ph rearrangements  in CML patients
      receiving tyrosine kinase inhibitor treatment.

PMID- 22989956
TI  - A fundamental mechanism of legged locomotion with hip torque and leg damping.
AB  - New models and theories of legged locomotion are needed to better explain and
      predict the robustly stable legged locomotion of animals and some bio-inspired
      robots. In this paper we observe that a hip-torque and leg-damping mechanism is
      fundamental to many legged robots and some animals and determine its affect on
      locomotion dynamics. We discuss why this hip-torque-and-leg-damping mechanism is
      not so easily understood. We investigate how hip-torque and leg-damping affect
      the stability and robustness of locomotion using a mathematical model: First, we
      extend the canonical spring-loaded-inverted-pendulum model to include constant
      hip torque and leg damping proportional to leg length speed. Then, we calculate
      the stability and robustness of locomotion as a function of increasing levels of
      torque and damping, starting from zero-the energy conserving and marginally
      stable special case-to high levels of torque and damping. We find that the
      stabilizing effects of hip-torque and leg-damping occur in the context of the
      piecewise-continuous dynamics of legged locomotion, and so linear intuition does
      not apply. We discover that adding hip torque and leg damping changes the
      stability of legged locomotion in an unexpected way. When a small amount of
      torque and damping are added, legged locomotion is initially destabilized. As
      more torque and damping are added, legged locomotion turns stable and becomes
      increasingly more stable and more robust the more torque and damping are added.
      Also, stable locomotion becomes more probable over the biologically-relevant
      region of the parameter space, indicating greater prediction and explanatory
      capabilities of the model. These results provide a more clear understanding of
      the hip-torque-and-leg-damping mechanism of legged locomotion, and extend
      existing theory of legged locomotion towards a greater understanding of robustly
      stable locomotion.

PMID- 22989957
TI  - Intermittent general anesthesia with controlled ventilation for asleep-awake
      asleep brain surgery:  a prospective series of 140 gliomas in eloquent areas.
AB  - BACKGROUND: Awake brain tumor surgery is a unique opportunity for mapping
      sensorimotor and cognitive functions, allowing the operator to optimize the
      resection while preserving the patient's quality of life. During this type of
      procedure, active participation of the patient is necessary. OBJECTIVE: To assess
      the efficacy and safety of a method of intermittent general anesthesia with
      controlled ventilation for performing invasive cerebral mapping. METHODS: We
      report our prospective and observational single-center study with an asleep-awake
      asleep protocol. Aspects of feasibility, airway management, timing of each phase,
      and occurrence of adverse events were detailed. RESULTS: During a 35-month
      period, 140 patients underwent resection of a glioma in an eloquent area. During
      the asleep phases, controlled ventilation with a laryngeal mask was always
      efficient. Orotracheal intubation was performed for some patients for the second
      asleep period. The patients remained fully awake for a mean time of 98 minutes.
      Postural discomfort was reported in 17.8% of cases. There was 1 case of
      aspiration of gastric contents with a favorable outcome and no mortality.
      CONCLUSION: Intermittent general anesthesia with controlled ventilation for this
      type of neurosurgical procedure remains an anesthesiological challenge. However,
      the results of this study suggest that it may be feasible, reproducible, and
      relatively safe in the context of a standardized protocol involving members of
      both anesthesiology and surgery teams. Such a technique has a great potential to
      improve the surgical results, from both oncological and functional perspectives.

PMID- 22989958
TI  - Safety and efficacy of onyx embolization for pediatric cranial and spinal
      vascular lesions and tumors.
AB  - BACKGROUND: Although Onyx is widely used to embolize vascular lesions in adults,
      the safety and efficacy of this liquid embolic agent for use in children are not
      well studied. OBJECTIVE: To report our experience using Onyx in pediatric
      patients for a variety of cranial and spinal vascular lesions and tumors to
      determine its procedural complication rates, types, and clinical consequences and
      to highlight the indications for and principles of Onyx embolization in pediatric
      patients. METHODS: All pediatric Onyx embolization cases performed consecutively
      by the neuroendovascular services at our 2 institutions over a 5-year period were
      collected retrospectively and analyzed. RESULTS: Over the study period, 105 Onyx
      embolization procedures were performed in 69 pediatric patients with a mean
      follow-up of 112 days. Fifty-two patients harbored "primary" vascular lesions
      (malformations, fistulas, etc), whereas 17 patients had tumors. Complications
      occurred in 25 of 105 procedures (23.8%) and included ischemic infarct (7),
      asymptomatic nontarget embolization (4), intracerebral hemorrhage (3),
      microcatheter-related vessel perforation (3), retained microcatheter (2),
      cerebral edema (2), dimethyl sulfoxide-induced pulmonary edema (2), facial
      ischemia (1), and contrast-induced bronchospasm (1). Neurological morbidity
      occurred transiently after 10 procedures (9.5%) and permanently after 2
      procedures (1.9%). There were no procedure-related deaths. Statistical analysis
      revealed no predictors of complications among the multiple potential risk factors
      evaluated. CONCLUSION: Our experience suggests that Onyx can be used effectively
      for embolization of pediatric cranial and spinal vascular lesions and tumors with
      low permanent morbidity; however, attention must be paid to the technical nuances
      of and indications for its use to avoid potential complications.

PMID- 22989959
TI  - Frameless, real-time, surface imaging-guided radiosurgery:  clinical outcomes for
      brain metastases.
AB  - BACKGROUND: Frameless stereotactic radiosurgery is commonly used to treat
      intracranial metastases, but mask-based immobilization can be uncomfortable for
      patients. OBJECTIVE: To describe the clinical outcomes using a novel real-time,
      frameless, surface imaging--guided radiosurgery (SIG-RS) technique to treat brain
      metastases. METHODS: Data were prospectively gathered for 44 consecutive patients
      totaling 115 intracranial metastases treated with SIG-RS in a median of 1
      fraction (range, 1-5) to a median dose of 20 Gy (range, 15-30 Gy). Local control,
      regional control, and overall survival were estimated by the Kaplan-Meier method.
      RESULTS: Median follow-up for all patients was 6.0 months (range, 0.3-21.6
      months), with 31 of 44 (70%) deceased at the time of analysis. The 35 patients
      (80%) with follow-up imaging totaled 88 lesions evaluable for local control.
      Actuarial 6- and 12-month local control was 90% (95% confidence interval, 82-98)
      and 76% (95% confidence interval, 60-91), respectively. Regional failure was
      observed in 16 patients (46%). The median actuarial overall survival was 7.7
      months (95% confidence interval, 5.7-9.7). Analysis of the subset of 22 patients
      (55 lesions) who received SIG-RS alone (no prior treatment) in a single fraction
      yielded comparable clinical outcomes. Grade 3 or greater toxicity occurred in 4
      patients (9%). The median treatment time from beam on to beam off was 15 minutes
      (range, 3-36 minutes). CONCLUSION: SIG-RS for treating intracranial metastases
      can produce clinical outcomes comparable to those with conventional frame-based
      and frameless stereotactic radiosurgery techniques while providing greater
      patient comfort with an open-faced mask and fast treatment times.

PMID- 22989960
TI  - Assessment of symptomatic rod fracture after posterior instrumented fusion for
      adult spinal deformity.
AB  - BACKGROUND: Improved understanding of rod fracture (RF) in adult spinal deformity
      could be valuable for implant design, surgical planning, and patient counseling.
      OBJECTIVE: To evaluate symptomatic RF after posterior instrumented fusion for
      adult spinal deformity. METHODS: A multicenter, retrospective review of RF in
      adult spinal deformity was performed. Inclusion criteria were spinal deformity,
      age older than 18 years, and more than 5 levels posterior instrumented fusion.
      Rod failures were divided into early (<=12 months) and late (>12 months).
      RESULTS: Of 442 patients, 6.8% had symptomatic RF. RF rates were 8.6% for
      titanium alloy, 7.4% for stainless steel, and 2.7% for cobalt chromium. RF
      incidence after pedicle subtraction osteotomy (PSO) was 15.8%. Among patients
      with a PSO and RF, 89% had RF at or adjacent to the PSO. Mean time to early RF
      (63%) was 6.4 months (range, 2-12 months). Mean time to late RF (37%) was 31.8
      months (range, 14-73 months). The majority of RFs after PSO (71%) were early
      (mean, 10 months). Among RF cases, mean sagittal vertical axis improved from
      preoperative (163 mm) to postoperative (76.9 mm) measures (P<.001); however, 16
      had postoperative malalignment (sagittal vertical axis>50 mm; mean, 109 mm).
      CONCLUSION: Symptomatic RF occurred in 6.8% of adult spinal deformity cases and
      in 15.8% of PSO patients. The rate of RF was lower with cobalt chromium than with
      titanium alloy or stainless steel. Early failure was most common after PSO and
      favored the PSO site, suggesting that RF may be caused by stress at the PSO site.
      Postoperative sagittal malalignment may increase the risk of RF.

PMID- 22989961
TI  - Venous sinus pulsatility and the potential role of dural incompetence in
      idiopathic intracranial hypertension.
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH) remains a poorly
      understood and therapeutically challenging disease. Enthusiasm has emerged for
      endovascular therapy with stent reconstruction of dural sinus narrowing; however,
      a complete understanding of the hydrodynamic dysequilibrium is lacking.
      OBJECTIVE: To review and characterize catheter manometry findings including
      pulsatility changes within the venous sinuses in IIH. METHODS: Cases of venous
      sinus stent implantation for IIH were retrospectively reviewed. RESULTS: Three
      cases of venous sinus stent implantation for treatment of IIH are reported. All
      cases demonstrated severe narrowing (>70%) within the transverse sinus and a high
      pressure gradient across the lesion (>30 mm Hg). Stent implantation resulted in
      pulsatility attenuation, correction of pressure gradient, and improvement of
      flow. CONCLUSION: We report the finding of high venous sinus pulsatility
      attenuation after stent implantation for dural sinus narrowing and propose the
      hypothesis that this finding is a marker of advanced dural sinus incompetence.
      This characteristic may be useful in identifying patients who would benefit from
      endovascular stent remodeling.

PMID- 22989964
TI  - Gene therapy for aromatic L-amino acid decarboxylase deficiency.

PMID- 22989965
TI  - Clinical decision support systems: key to making EHR an improvement.

PMID- 22989966
TI  - The role of the basal ganglia in decision making: a new fMRI study.

PMID- 22989967
TI  - Attending feedback after surgery:  an under-utilized force in surgical education.

PMID- 22989968
TI  - EGFR targeted inhibition resistance: compensatory activation of ERBB family
      members in glioblastoma cancer stem-like cells promotes proliferation.

PMID- 22989969
TI  - Having the brain participate in spinal cord injury recovery.

PMID- 22989970
TI  - Recovery of cortical control over locomotion after spinal cord injury.

PMID- 22989972
TI  - Tumor-specific targeted therapy in pediatric astrocytoma demonstrated in a murine
      model.

PMID- 22989973
TI  - The natural course of unruptured cerebral aneurysms.

PMID- 22989974
TI  - Dorsal anterior cingulate cortex neurons as the basis for the Gratton effect: a
      unique study of human cognition.

PMID- 22989975
TI  - Evaluation of an art in health care elective module--a nurse education
      initiative.
AB  - BACKGROUND: International literature suggests that nurse educators perceive a
      value in the arts and literature as a teaching strategy in helping nurses express
      a personal philosophy of nursing, teaching spirituality and non-verbal
      communication. PURPOSE OF STUDY: The purpose of this study was to evaluate
      nursing students experiences of undertaking an interdisciplinary 'Art in Health'
      elective. STUDY DESIGN: The formative evaluation approach was based on the
      reflective practice model that encourages students (n = 60) to evaluate their own
      learning experience. FINDINGS: 88% of nursing students valued the experience of
      learning with students from other disciplines or colleges. 63% commented on how
      they enjoyed the creative aspect of studio work and the element of diversity in
      brought to nursing. 63% indicated that the module gave them a greater insight
      into the presence of art in health care contexts and felt that they gained a
      deeper understanding of how art can help people in hospital. CONCLUSION: The
      module presents an innovative model of interdisciplinary curriculum development
      which appears to facilitate students in viewing patients from a more holistic
      perspective. As an education experience this module appears to have the potential
      to help students develop skills in working collaboratively with other health care
      and non health care disciplines.

PMID- 22989976
TI  - Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions
      prepared by nanoprecipitation/homogenization based on acid-base neutralization.
AB  - In this study, aripiprazole (APZ), a weak alkaline drug with pH-dependent
      solubility, was selected as model drug to examine the feasibility of preparing
      nanosuspensions using nanoprecipitation/homogenization technique based on acid
      base neutralization. The related substances in nanosuspensions prepared under
      optimal conditions were slightly increased as compared with APZ raw material. The
      resultant APZ nanosuspensions showed a mean particle size of 350 nm with
      polydispersion index (PI) value of 0.20. Good physical stability was kept for
      over 40 days. SEM observation showed the morphology of oval crystals with rough
      surface. Nanosuspensions significantly increased the solubility as well as the
      dissolution of APZ due to the decreased particle size. Differential scanning
      calorimetry and powder X-ray diffractometry confirmed the crystallinity of APZ in
      nanosuspensions. APZ nanosuspensions got maximum absorption rate and extent
      comparing with APZ commercial tablet and suspensions with relative
      bioavailability of 123.43 +/- 12.98% and 171.41 +/- 14.62%, respectively. This
      technique has the potential to prepare nanosuspensions of insoluble drugs with pH
      dependent solubility.

PMID- 22989977
TI  - Characterization and molecular modeling of the inclusion complexes of 2-(2
      nitrovinyl) furan (G-0) with cyclodextrines.
AB  - The objective of this study was to prepare and characterize complexes of 2-(2
      nitrovinyl) furan (G-0) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and
      sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD). The solid inclusion complexes
      were prepared using kneading and freeze-drying methods. Phase solubility profiles
      were used to obtain the apparent stability constants and the complexation
      efficiency. They were classified as A(L) type for both systems: the apparent
      stability constants K(1:1) of the complexes were 48.7 and 79.2 M(-1) for HP-beta
      CD and SBE-beta-CD respectively. The solid inclusion complexes were evaluated by
      means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and
      nuclear magnetic resonance spectroscopy (NMR). Especially the use of the two
      dimensional ROESY spectrum was useful to confirm the presence of an inclusion
      complex. The spatial configuration of the drug inside the cyclodextrin cavity was
      investigated using molecular modeling studies. The latter results were in
      agreement with the experimental data. Inclusion complexes of G-0 with HP-beta-CD
      contributed to improve the chemical stability of the drug in the presence of
      other commonly used pharmaceutical excipients.

PMID- 22989978
TI  - Coformer selection based on degradation pathway of drugs: a case study of
      adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals.
AB  - Adefovir dipivoxil (AD) is a bis(pivaloyloxymethyl) prodrug of adefovir with
      chemical stability problem. It undergoes two degradation pathways including
      hydrolysis and dimerization during storage. Pharmaceutical cocrystallization
      exhibits a promising approach to enhance aqueous solubility as well as
      physicochemical stability. In this study we attempted to prepare and investigate
      the physiochemical properties of AD cocrystals, which were formed with two
      coformers having different acidity and alkalinity (weakly acidic saccharin (SAC)
      and weakly basic nicotinamide (NCT)). The presence of different coformer
      molecules along with AD resulted in altered physicochemical properties. AD-SAC
      cocrystal showed great improvement in solubility and chemical stability, while AD
      NCT did not. Several potential factors giving rise to different solid-state
      properties were summarized. Different coformers resulted in different cocrystal
      formation, packing style and hydrogen bond formation. This study could provide
      the coformer selection strategy based on degradation pathways for some unstable
      drugs in pharmaceutical cocrystal design.

PMID- 22989979
TI  - A single injection of liposomal asialo-erythropoietin improves motor function
      deficit caused by cerebral ischemia/reperfusion.
AB  - Modification of the liposomal surface with a targeting molecule is a promising
      approach for the targeted delivery of therapeutics. Asialo-erythropoietin (AEPO)
      is a potent tool for targeting an ischemic region by binding to the EPO receptors
      on neuronal cells. Additionally, it shows a strong cytoprotective effect against
      programed cell death. Hence, AEPO-modified liposomes appear likely to have both a
      neuronal-targeting character and a neuroprotective effect on cerebral ischemic
      injury. In this study, we assessed the targeting ability of AEPO-modified
      PEGylated liposomes (AEPO-liposomes) to ischemic region and their improvement
      effect on neurological deficits induced by ischemia/reperfusion (I/R) in
      transient middle cerebral artery occlusion (t-MCAO) rats. Immunohistological
      analysis showed that the AEPO-liposomes given immediately after reperfusion
      extravasated into the ischemic region and attached strongly to neuronal cells.
      Also, neuronal nuclei (NeuN) staining was clearly visible only in the AEPO
      liposome-treated group, suggesting that AEPO-liposomes protected neuronal cells
      from ischemia/reperfusion-induced damage. Moreover, a single administration of
      low-dose AEPO-liposomes significantly improved the neurological deficit compared
      to vehicle and free-AEPO treatment at 7 days after injection. In conclusion, AEPO
      liposomes have clear potential as a neuroprotectant after stroke and as a DDS
      device targeting ischemic regions.

PMID- 22989980
TI  - Ultrasonic real-time in-die monitoring of the tablet compaction process-a proof
      of concept study.
AB  - The mechanical properties of a drug tablet can affect its performance (e.g.,
      dissolution profile and its physical robustness. An ultrasonic system for real
      time in-die tablet mechanical property monitoring during compaction has been
      demonstrated. The reported set-up is a proof of concept compaction monitoring
      system which includes an ultrasonic transducer mounted inside the upper punch of
      the compaction apparatus. This upper punch is utilized to acquire ultrasonic
      pressure wave phase velocity waveforms and extract the time-of-flight of pressure
      waves travelling within the compact at a number of compaction force levels during
      compaction. The reflection coefficients for the waves reflecting from punch tip
      powder bed interface are extracted from the acquired waveforms. The reflection
      coefficient decreases with an increase in compaction force, indicating
      solidification. The data acquisition methods give an average apparent Young's
      moduli in the range of 8-20 GPa extracted during the compaction and
      release/decompression phases in real-time. A monitoring system employing such
      methods is capable of determining material properties and the integrity of the
      tablet during compaction. As compared to the millisecond time-scale dwell time of
      a typical commercial compaction press, the micro-second pulse duration and ToF of
      an acoustic pulse are sufficiently fast for real-time monitoring.

PMID- 22989981
TI  - Porous core/sheath composite nanofibers fabricated by coaxial electrospinning as
      a potential mat for drug release system.
AB  - This study focused on fabrication and characterization of porous core/sheath
      structured composite nanofibers with a core of blended salicylic acid (SA) and
      poly(ethylene glycol) (PEG) and a sheath of poly(lactic acid) (PLA) using a dual
      capillary electrospinning system. Results of water contact angle measurements,
      field-emission scanning electron microscopy, and transmission electron microscopy
      indicated that feed rates of the core and sheath strongly affect the stability of
      the core/sheath structure and porous density of the composite nanofibers
      obtained, significantly influencing their SA release characteristics. At a lower
      ratio of feed rates of the core and the sheath, better stable core/sheath
      structures of nanofibers with higher porous density on the surface were formed
      resulting in a sustained release of SA over 5 days. Non-porous fibers showed a
      lower amount of drug release because the drug was embedded inside the core layer
      of the non-porous sheath layer. SA release from porous core/sheath nanofibers was
      described based on a one-dimensional Fickian diffusion mechanism, indicating that
      drug diffusion is a predominant factor in drug release. A cytotoxicity test
      suggested that the porous core/sheath nanofibers are non-toxic and support cell
      attachment. Therefore, this fiber mat may find application in the design of wound
      healing patches with long-term activity.

PMID- 22989982
TI  - Evaluation of thermoresponsive properties and biocompatibility of
      polybenzofulvene aggregates for leuprolide delivery.
AB  - In this study, a polybenzofulvene derivative named poly-6-MOEG-9-BF3k, was
      evaluated as polymeric material for the production of injectable thermoresponsive
      nano-aggregates able to load low molecular weight peptidic drug, like the
      anticancer leuprolide. Thermoresponsive behavior of poly-6-MOEG-9-BF3k was
      studied in aqueous media by evaluating scattering intensity variations by means
      of DLS in function of temperature. Zeta potential measurements and SEM
      observations were also carried out. Moreover, critical aggregation temperature of
      the poly-6-MOEG-9-BF3k polymer was evaluated by pyrene fluorescence analysis.
      Then, the ability of prepared thermoresponsive aggregates to protect this model
      oligopeptide drug and regulate its release rate in function of external
      temperature was evaluated in vitro. Finally, biocompatibility of poly-6-MOEG-9
      BF3k aggregates was tested in vitro on a healthy cell line (human bronchial
      epithelial cell; 16-HBE) and in vivo on rat animal model upon subcutaneous
      administration.

PMID- 22989983
TI  - Formation of a physical stable delivery system by simply autoclaving
      nanostructured lipid carriers (NLC).
AB  - A unique long term stable carrier system for poorly soluble drugs was obtained by
      simply autoclaving nanostructured lipid carriers (NLC). NLC composed of Precirol
      ATO, oleic acid, glycerol 85%, Eumulgin SML 20 and water as well as NLC loaded
      with the poorly soluble drug Itraconazole formed a special organized matrix
      containing lamellar bilayers similar to biological membranes after the
      sterilization process. The tendency to expel the poorly soluble drug from the
      matrix was thereby avoided.

PMID- 22989984
TI  - Protein release from poly(lactide-co-glycolide) implants prepared by hot-melt
      extrusion: thioester formation as a reason for incomplete release.
AB  - The aim of this study was to characterize the protein release from PLGA-based
      implants prepared by hot-melt extrusion with special emphasis on identifying
      reasons for incomplete release. Biodegradable PLGA-implants loaded with BSA were
      prepared with a syringe-die extrusion device. A burst-free release was achieved
      up to 25% BSA loading by milling the protein prior to extrusion. The release was
      incomplete at 70% at loadings below the percolation threshold of the protein;
      higher protein loadings increased the release to 97%. However, an insoluble
      implant mass remained for over 180 days, which was attributed to the acylation of
      BSA by PLGA oligomers via a thioester bond. The incomplete protein release due to
      the formation of this covalent bond was overcome when increasing the porosity of
      the implant, which effectively reduced the contact between BSA and PLGA
      oligomers. Accordingly, melt-extrusion facilitated incorporating high loadings of
      BSA into burst-free biodegradable implants. Additionally, it enhanced complete
      protein release by a process- or formulation controlled increase of the implant
      porosity.

PMID- 22989985
TI  - Assembled nanomedicines as efficient and safe therapeutics for articular
      inflammation.
AB  - Highly efficient nanomedicines were successfully fabricated by the indomethacin
      (IND) directed self-assembly of beta-cyclodextrin (beta-CD)-conjugated
      polyethyleneimine (PEI-CD), taking advantage of the multiple interactions between
      drug and polymer. These nanoscaled assemblies exhibited spherical shape and
      positively charged surface. Compared with the commercial tablet, the relative
      oral bioavailability of IND-nanomedicines was significantly enhanced. Evaluation
      based on either carrageenan-induced paw edema or complete Freund's adjuvant (CFA)
      induced arthritis suggested the newly developed nanomedicines were more effective
      than raw IND or IND tablet in terms of prophylactic effect and therapeutic
      activity. Even the low dose of nanomedicines offered the comparable results to
      those of control groups at the high dosage in most cases. Moreover, the
      nanoformulation exhibited ameliorated gastrointestinal stimulation. All these
      positive results indicated that this type of nanomedicines might serve as a
      highly efficient and effective delivery nanoplatform for the oral delivery of
      water-insoluble therapeutics.

PMID- 22989986
TI  - A comparison of quality control methods for active coating processes.
AB  - Terahertz pulsed imaging (TPI) is a recent and nondestructive technique to
      quantify coating thickness of pharmaceutical tablet film coatings. In this study,
      TPI is used for the first time to quantify the progress of an active coating
      process. The dosage form consisted of a push-pull osmotic system comprising a two
      layer tablet core with a functional film coating and a laser drilled hole. On top
      of this system an active coating was applied. The coating thickness data acquired
      by TPI and optical microscopy was compared to the quantification of the active
      pharmaceutical ingredient (API) via HPLC. Good correlation of TPI and HPLC data
      was shown for coating thicknesses up to 500 MUm. Due to the special structure of
      the dosage form, the TPI detection limit of 38 MUm layer thickness was
      circumvented by analysing the coating thickness of active coating and functional
      subcoat in one. Therefore it was possible to monitor the active coating process
      from the very beginning of the process. Optical microscopy was no suitable
      reference technique for TPI thickness measurements. The active coating showed
      deformation artefacts during sample preparation, which biased the subsequent
      thickness measurements.

PMID- 22989987
TI  - Nanostructured lipid carriers (NLC) based topical gel of flurbiprofen: design,
      characterization and in vivo evaluation.
AB  - Nanostructured lipid carriers (NLC)-based gel was developed as potential topical
      system for flurbiprofen (FP) topical delivery. The characterizations of the
      prepared semisolid formulation for topical application on skin were assessed by
      means of particle size distribution, zeta potential analysis, X-ray analysis, in
      vitro percutaneous penetration, rheological study, skin irritation test, in vivo
      pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained
      within the colloidal range and it was uniformly dispersed after suitably gelled
      by carbopol preparation. It was indicated in vitro permeation studies through rat
      skin that FP-NLC-gel had a more pronounced permeation profile compared with that
      of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for
      all NLC-gels after storage at three different temperatures. No oedema and
      erythema were observed after administration of FP-NLC-gel on the rabbit skin, and
      the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum
      concentration in plasma was 29.44 MUg/ml and 2.49 MUg/ml after oral and topical
      administration, respectively. While the amount of drug accumulated in skin after
      topical application was much higher than oral application. In conclusion, NLC
      based gel could be a promising vehicle for topical delivery of FP.

PMID- 22989988
TI  - [Long-term use of silicone oil: indications and tolerance].
AB  - PURPOSE: The aim of this study was to analyze the indications and the effect of
      permanently maintaining silicone oil in the treatment of certain cases of
      vitreoretinal pathology. PATIENTS AND METHODS: Twenty-seven cases seen from
      January 2002 to December 2008 were retrospectively studied. Silicone oil was kept
      in the eyes for more than 2years. The surgical file was analyzed in all cases.
      The evaluation criteria were ocular pressure, emulsification, cataract, corneal
      dystrophy, and the functional response of the retina and optic nerve. Ultrasound
      echography (12 MHz), magnetic resonance imaging, and electrophysiological
      explorations (visual evoked potential and electroretinography) were performed.
      RESULTS: Twenty-seven eyes of 27 patients were included in this study. The main
      reasons for maintaining long-term silicone oil are recurrent vitreous hemorrhage,
      retinal detachment with severe proliferative vitreoretinopathy, and penetrating
      injury. The patients were distributed into two groups: group 1 included patients
      with both functional and anatomic failure, group 2 patients had achieved
      ambulatory vision. Follow-up ranged from 27 to 72months. Cataract incidence was
      approximately 91% in group 2. Emulsification was noted without high pressure in
      50% of the cases in group 1. High pressure averaged 31.8% in group 2. Keratopathy
      was observed in 9% of the cases in group 2. Intraorbital migration of silicone
      oil was found in one case. The visual field was improved in 77% of the cases in
      group 2. CONCLUSION: This study provided interesting insights into certain
      clinical situations in which silicone oil has to be maintained permanently. The
      complications stem not only from the presence of silicone oil, but also from the
      preoperative status of the eye and the vitreoretinal surgery.

PMID- 22989989
TI  - Stability, interaction and influence of domain boundaries in Ge/Si(111)-5 * 5.
AB  - We present a theoretical investigation of the influence of domain boundaries on
      the Ge/Si(111)-5 * 5 phase using both large-scale DFT simulations and an
      analytical model. It is shown that different boundary types modify the atomic and
      electronic structure of the adjoining 5 * 5 domains in very different ways. A
      simple theoretical model, that describes the energy interaction J between the
      boundaries and the 5 * 5 phase, is presented and the interaction energy decay
      J(x) ~ x(-n) for different domain boundaries is estimated. Additionally, the
      influence of the boundaries on the atomic and electronic structure of adatoms in
      the parental 5 * 5 phase is analyzed and it is argued that the presence of domain
      boundaries may strongly affect not only the physical but also the chemical
      properties of the Ge/Si(111)-5 * 5 phase.

PMID- 22989991
TI  - Challenges in electrochemical pre-purification of recombinant proteins from green
      plant tissues: sgfp produced in tobacco leaves.
AB  - The use of recombinant proteins has increased greatly in recent years, as have
      the number of techniques and materials used for their production and
      purification. The principal advantage of using plants as bioreactors is the cost
      of the recombinant protein production, which is about 1000-fold lower as in the
      case of using CHO cells commonly applied in industry today. Among the different
      types of "green" bioreactors being studied today, there is a general consensus
      among scientists that production in green plant tissues such as leaves is more
      feasible. However, the presence of chlorophyll and phenolic compounds in plant
      extracts, which can precipitate and denature the proteins besides damaging
      separation membranes and gels, makes this technology impracticable on a
      commercial scale. Electrochemically produced aluminium hydroxide gel can be used
      to adsorb these compounds, and pre-purify recombinant synthetic green fluorescent
      protein (sGFP) produced in Nicotiana benthamiana leaves. Removal efficiencies of
      99.7% of chlorophyll, 88.5% of phenolic compounds, and 38.5% of native proteins
      from the N. benthamiana extracts were achieved without removing sGFP from the
      extracts. Since electrochemical preparation of aluminum hydroxide gel is a cost
      effective technique, its use can substantially contribute to the development of
      future production platforms for recombinant proteins produced in green plant
      tissues of pharmaceutical and industrial interest.

PMID- 22989990
TI  - CHO-gmt5, a novel CHO glycosylation mutant for producing afucosylated and
      asialylated recombinant antibodies.
AB  - Engineered zinc-finger nucleases (ZFNs) are powerful tools for creating double
      stranded-breaks (DSBs) in genomic DNA in a site-specific manner. These DSBs
      generated by ZFNs can be repaired by homology-directed repair or nonhomologous
      end joining, in which the latter can be exploited to generate insertion or
      deletion mutants. Based on published literature, we designed a pair of zinc
      finger nucleases and inactivated the GDP-fucose transporter gene (Slc35c1) in a
      previously reported CHO mutant that has a dysfunctional CMP-sialic acid
      transporter gene (Slc35a1). The resulting mutant cell line, CHO-gmt5, lacks
      functional GDP-fucose transporter and CMP-sialic acid transporter. As a result,
      these cells can only produce asialylated and afucosylated glycoproteins. It is
      now widely recognized that removal of the core fucose from the N-glycans attached
      to Asn(297) of human IgG1 significantly enhances its binding to its receptor,
      FcgammaRIIIa, and thereby dramatically improves antibody-dependent cellular
      cytotoxicity (ADCC). Recent reports showed that removal of sialic acid from IgG1
      also enhances ADCC. Therefore, CHO-gmt5 may represent a more advantageous cell
      line for the production of recombinant antibodies with enhanced ADCC. These cells
      show comparable growth rate to wild type CHO-K1 cells and uncompromised
      transfection efficiency, which make them desirable for use as a production line.

PMID- 22989992
TI  - Designing industrial yeasts for the consolidated bioprocessing of starchy biomass
      to ethanol.
AB  - Consolidated bioprocessing (CBP), which integrates enzyme production,
      saccharification and fermentation into a one step process, is a promising
      strategy for the effective ethanol production from cheap lignocellulosic and
      starchy materials. CBP requires a highly engineered microbial strain able to both
      hydrolyze biomass with enzymes produced on its own and convert the resulting
      simple sugars into high-titer ethanol. Recently, heterologous production of
      cellulose and starch-degrading enzymes has been achieved in yeast hosts, which
      has realized direct processing of biomass to ethanol. However, essentially all
      efforts aimed at the efficient heterologous expression of saccharolytic enzymes
      in yeast have involved laboratory strains and much of this work has to be
      transferred to industrial yeasts that provide the fermentation capacity and
      robustness desired for large scale bioethanol production. Specifically, the
      development of an industrial CBP amylolytic yeast would allow the one-step
      processing of low-cost starchy substrates into ethanol. This article gives
      insight in the current knowledge and achievements on bioethanol production from
      starchy materials with industrial engineered S. cerevisiae strains.

PMID- 22989993
TI  - Paediatric angiodysplasia of the jejunum: a case report and review of the
      literature.
AB  - Gastrointestinal angiodysplasia (GIAD) of the jejunum is a rare cause of acute
      upper and lower gastrointestinal bleeding in the paediatric population. This is
      the case of a previously well 10-year-old girl who presented with acute rectal
      haemorrhage, haematemesis and syncope. Despite an exploratory laparotomy, the
      cause of bleeding remained unknown. A computerized tomography angiogram was
      performed once she was haemodynamically stable. It indicated bleeding in the
      jejunum. Repeat laparotomy was performed including enterotomy, copious small
      bowel washout and visualization of the whole small bowel. The lesion was
      identified at approximately 100 cm from the duodenojejunal flexure and confirmed
      by isolating the lesion and testing for bleeding. A 30 cm length of jejunum was
      resected and primary anastomosis performed. She recovered well and was discharged
      three days postoperatively. She remained well at six-month follow-up. This case
      highlights the importance of considering upper GIAD in an acute paediatric
      gastrointestinal bleed and the way in which surgical management can prevent a
      potentially fatal outcome.

PMID- 22989994
TI  - A series of experiments aimed at clarifying the mode of action of barley straw in
      cyanobacterial growth control.
AB  - For over 25 years it has been known that rotting barley straw can be used to
      prevent the development of blooms of cyanobacteria and algae in freshwater
      bodies, although its effectiveness can be variable. The mode of action is still
      not understood, although a number of hypotheses have been suggested, many of
      which are supported by little or no experimental evidence. Here, we provide the
      first experimental confirmation that microbial activity is responsible for the
      release of either the growth inhibitory fraction, or its precursor, from whole
      straw, after three or more weeks of decomposition. However, a much more rapid
      release of inhibitory components was achieved by fine chopping of fresh straw. In
      bioassays of straw activity the choice of both the cyanobacterial test strain and
      the assay temperature affected the outcome. The inhibitory activity of straw was
      greater when decomposition was carried out in the presence of UV-supplemented
      visible light and this activity was reduced in the presence of catalase, implying
      that straw activity may in part involve hydrogen peroxide. A better understanding
      of straw decomposition is required to clarify the mode of action of straw and
      allow the optimisation of its use in the field.

PMID- 22989995
TI  - Novel extraction of volatile biomarkers from canine breath for gas chromatography
      mass spectrometry.
AB  - Here we describe an effective, reproducible, non-invasive volatile organic
      compound collection and analysis method for exhaled breath gas samples designed
      specifically for use with dogs. Conditions of the method were optimized, using a
      range of standard chemicals. This method utilizes a canine mask, two-way non-re
      breathing valve, teflon connector, tubing and bag for sample collection.
      Collection is followed by condensation and headspace solid phase microextraction
      for sample concentration and gas chromatography-mass spectrometry for analysis.
      Custom-made glassware, designed to hold the SPME fiber assembly, was cooled to 
      10  degrees C and used for the collection of the condensate followed by 2 h of
      headspace extraction at 37  degrees C. Standards show LOD of 0.6-16.8 ppbv, LOQ
      between 2.1-55.8 ppbv, and good linearity with R(2) between 0.996-0.999 (RSD% 10
      19). The method was verified with preliminary results from three dogs
      demonstrating that this technique is capable of collecting, identifying and
      quantifying volatile organic chemical constituents in different breath samples.

PMID- 22989997
TI  - Expression of complement receptors 1 (CR1/CD35) and 2 (CR2/CD21), and co
      signaling molecule CD19 in cattle.
AB  - C3d is a sub-fragment of the C3 component of the complement system. Covalent
      binding of multiple C3ds to antigen reduces the activation threshold of cognate B
      lymphocytes by one thousand fold through co-ligation of the B cell antigen
      receptor (BCR) and complement receptor 2 (CR2/CD21). Reverse transcriptase
      polymerase chain reaction (RT-PCR) revealed that, in cattle, four distinct
      complement receptors are produced from the Cr2 gene by alternative splicing.
      Cattle express two major variants of the Cr2 gene representing homologues of
      murine CR1 and CR2, each of which is expressed in both a long and a short form.
      Expression of CR1 and CR2 was detected in IgM(+) cells from both the spleen and
      peripheral blood. Additionally, the coding sequence of CD19, the CR2 co-signaling
      molecule, was determined. CD19 was confirmed to be expressed by IgM(+) cells from
      the spleen and peripheral blood.

PMID- 22989998
TI  - MULAN related gene (MRG): a potential novel ubiquitin ligase activator of NF-kB
      involved in immune response in Atlantic salmon (Salmo salar).
AB  - Nuclear factor-kB (NF-kB) is a transcription factor that plays a central role in
      the regulation of a variety of genes including many involved in bacterial and
      viral infections. NF-kB is normally sequestered by inhibitory proteins (IkBs) in
      the cytoplasm of non-stimulated cells. The degradation of IkBs by the ubiquitin
      proteasome pathway releases NF-kB allowing its translocation to the nucleus where
      it regulates gene transcription. The Mitochondrial Ubiquitin Ligase Activator of
      NF-kB, (MULAN), is an E3 ubiquitin ligase involved in controlling activation of
      NF-kB, and regulating mitochondrial dynamics and apoptosis. We report the
      characterisation of a novel piscine-specific MULAN related gene (MRG) sequence,
      its mRNA tissue distribution and expression following in vivo and in vitro
      challenges. MRG cDNA was identified in Atlantic salmon and its sequence encodes a
      predicted protein of 274 amino acids. The mRNA of MRG was expressed in multiple
      tissues, with the highest abundance head kidney. An Aeromonas salmonicida
      bacterial challenge increased expression of this gene in head kidney, liver and
      gill tissue at 6 h and 24 h. In vitro stimulation of a salmonid cell line
      indicated MRG was increased in expression following stimulation with LPS, PolyI:C
      and recombinant trout IL-1beta for 4 h and 24 h. These results suggest an active
      role of MRG in the activation of the NF-kB pathway during early immune responses.

PMID- 22989999
TI  - Identification of knowledge gaps in neurosurgery using a validated self
      assessment examination: differences between general and spinal neurosurgeons.
AB  - OBJECTIVE: The practice of neurosurgery requires fundamental knowledge base.
      Residency training programs and continuing medical education courses are designed
      to teach relevant neurosurgical principles. Nevertheless, knowledge gaps exist
      for neurosurgeons and may be different between cohorts of neurosurgeons. The Self
      Assessment in Neurological Surgery (SANS) General Examination and Spine
      Examination are online educational tools for lifelong learning and maintenance of
      certification. This study examines the gaps in knowledge of spinal neurosurgeons
      and general neurosurgeons taking SANS. METHODS: From 2008 to 2010, a total of 165
      spinal neurosurgeons completed the 243 available questions of the SANS Spine
      Examination. Over that same time frame, 993 general neurosurgeons completed the
      SANS General Spine Examination. Mean scores were calculated and assessed
      according to 18 major neurosurgical knowledge disciplines. Statistical analysis
      was carried out to evaluate for significant knowledge gaps among all users and
      significant differences in performance between spinal neurosurgeons and their
      general neurosurgeon counterparts. RESULTS: The mean overall examination score
      was 87.4% +/- 7.5% for spinal neurosurgeons and 71.5% +/- 8.9% for general
      neurosurgeons (P < 0.001). Of the 18 major knowledge categories in SANS, spinal
      neurosurgeons (n = 165) answered questions incorrectly 15% or greater of the time
      in five of the categories. The categories of lower performance for spinal
      neurosurgeons were cerebrovascular, anesthesia and critical care, general
      clinical, tumor, and trauma. For general neurosurgeons (n = 993), the five
      knowledge categories with lowest performance were cerebrovascular, epilepsy,
      peripheral nerve, trauma, and radiosurgery. Although spinal neurosurgeons and
      general neurosurgeons shared some areas of decreased performance including trauma
      and cerebrovascular, spine neurosurgeons relatively underperformed in general
      clinical, anesthesia and critical care, and tumor. CONCLUSIONS: The SANS Spine
      Examination demonstrated knowledge gaps in specific categories for spinal
      surgeons. The knowledge areas of diminished performance differed between spinal
      and general neurosurgeons. Identification of specific areas of deficiency could
      prove useful in the design and implementation of educational programs and
      maintenance of certification.

PMID- 22990000
TI  - Multimodal treatment of hemorrhagic pituitary metastasis as first manifestation
      of renal cell carcinoma.
AB  - BACKGROUND: Metastatic tumors involving the pituitary gland are very rare, with
      only few cases reported so far in the literature. CASE DESCRIPTION: We report a
      case of a man who presented with an extremely vascular hemorrhagic pituitary
      metastasis as the first manifestation of renal cell carcinoma. The patient was
      successfully treated with staged procedures, including preoperative tumor
      vasculature embolization followed by transsphenoidal tumor resection.
      CONCLUSIONS: This is the first report describing multimodality treatment of a
      patient with pituitary metastasis of unknown origin requiring presurgical
      embolization before successful tumor removal.

PMID- 22990001
TI  - Investigation of the influence of body weight index to the result of therapeutic
      erythrocytapheresis in patients with polycythemia vera.
AB  - We investigated the correlation between body weight index (BWI) and the effective
      power of erythrocytapheresis in patients with polycythemia vera (PV) who received
      therapeutic erythrocytapheresis (TEA). Furthermore, the risk factors of the
      adverse events related to erythroapheresis therapy were analyzed. Two hundred and
      seventeen cycles of therapeutic erythrocytapheresis were carried out in 139
      patients with PV (Hct). The correlation between the BWI and the difference of
      hematocrit before and after therapeutic erythrocytapheresis (DeltaHct) was
      analyzed by the Pearson correlation analysis method. Logistic regression analysis
      was used to study the risk factors of adverse events for TEA. We observed a
      positive correlation between the BWI and DeltaHct. BWI over 15 ml/kg, inlet
      velocity of the apheresis procedure over 45 ml/min and an age older than 50 years
      were the risk factors of adverse events of TEA. The results suggested that BWI
      was a sensitive index to estimate the effective power and adverse events of TEA.
      The rate of adverse events of TEA might be reduced by maintaining the BWI below
      the dangerous threshold of 15 ml/kg and the inlet velocity of the apheresis
      procedure below 45 ml/min especially in patients older than 50 years of age.

PMID- 22990002
TI  - Investigation of pseudogenes RHDPsi and RHD-CE-D hybrid gene in D-negative blood
      donors by the real time PCR method.
AB  - INTRODUCTION: The Rh system is the most polymorphic and immunogenic of all
      systems of blood groups. Currently more than 49 antigens were identified with
      five major antigens D, C, c, E, e. Knowledge of the molecular basis of the Rh
      system permitted the understanding of both the mechanism of Rh phenotype on the
      antigen variants of RHD and RHCE In Caucasians the primary mechanism of D
      negative phenotype is the complete deletion of RHD gene, while the black Africans
      is the presence of pseudogene and gene hybrid RHD-CE (3-7)-D. OBJECTIVE: To
      determine the prevalence gene pseudogene and hybrid gene and standardization of
      molecular techniques in method of Taqman on real-time PCR for RHD genotyping.
      PATIENTS AND METHODS: 203 samples of D-negative donor were used to establish and
      validate the effectiveness of RHD genotyping in real-time PCR using Taqman
      technology. The extraction was performed using a commercial kit QIAmp DNA mini
      kit. Samples exon 10 and 7 positive were submitted to amplification of exon 5,
      confirming the pseudogene RHDPsi, whereas exon 10+exon 7--for the hybrid gene (C)
      cdes and mutation C733G (Leu245Val) of the RHCE gene. RESULTS: Twenty-five
      (12.3%) samples were positive, 14 amplified for both exons 10 and 7 while in 11
      only for the exon 10. When extended the screening using exon 10, 7 and 5, only 06
      amplified. The pseudogene was present in 07 samples (3.5%) and the hybrid RHD-CE
      (3-7) in 04 (1.97%), while in 177 (87.2%) of Rh negative donors were RHD gene
      deletion. In 07 samples not amplified for exon 3 had mutated and the mutation
      C733G antigen. CONCLUSION: The prevalence of pseudogene was 3.5% and the gene
      hybrid RHD-CE of 1.9%. This approach for real-time PCR as a complementary tool is
      technically feasible and the results of this study helped develop a new strategy
      for RHD genotyping.

PMID- 22990003
TI  - Reaction times reflect subjective auditory perception of tone sequences in
      macaque monkeys.
AB  - Perceptually ambiguous stimuli are useful for testing psychological and neuronal
      models of perceptual organization, e.g. for studying brain processes that
      underlie sequential segregation and integration. This is because the same stimuli
      may give rise to different subjective experiences. For humans, a tone sequence
      that alternates between a low-frequency and a high-frequency tone is perceptually
      bistable, and can be perceived as one or two streams. In the current study we
      present a new method based on response times (RTs) which allows identification
      ambiguous and unambiguous stimuli for subjects who cannot verbally report their
      subjective experience. We required two macaque monkeys (macaca fascicularis) to
      detect the termination of a sequence of light flashes which were either presented
      alone, or synchronized in different ways with a sequence of alternating low and
      high tones. We found that the monkeys responded faster to the termination of the
      flash sequence when the tone sequence terminated shortly before the flash
      sequence and thus predicted the termination of the flash sequence. This RT gain
      depended on the frequency separation of the tones. RT gains were largest when the
      frequency separation was small and the tones were presumably heard mainly as one
      stream. RT gains were smallest when the frequency separation was large and the
      tones were presumably mainly heard as two streams. RT gain was of intermediate
      size for intermediate frequency separations. Similar results were obtained from
      human subjects. We conclude that the observed RT gains reflect the perceptual
      organization of the tone sequence, and that tone sequences with an intermediate
      frequency separation, as for humans, are perceptually ambiguous for monkeys.

PMID- 22990004
TI  - Transmission of carcinogenic human papillomavirus types from mother to child: a
      meta-analysis of published studies.
AB  - Currently, human papillomavirus (HPV) research focuses on HPV infection in adults
      and sexual transmission. Data on HPV infection in children are slowly becoming
      available. It is a matter of debate whether mother-to-child transmission of HPV
      is an important infection route and whether children born to HPV-positive mothers
      are at a higher risk of HPV infection compared with children born to HPV-negative
      mothers. The objective of this meta-analysis is to summarize the published
      literature on the extent to which genital HPV infection is vertically transmitted
      from mother to child. Medline, Web of Science, and CINAHL were searched for
      eligible reports published before January 2011. Differences in the risk of HPV
      infection between newborns from HPV-positive and HPV-negative mothers were pooled
      using a random-effects model. Twenty eligible studies, including 3128
      women/children pairs, fulfilled the selection criteria. High heterogeneity could
      be found (I=96%). The overall estimated risk difference was 33% (95% confidence
      interval: 22-44%). On restricting to high-risk HPV-positive mothers only (n=4;
      women=231), the difference in risk was 45% (95% confidence interval: 33-56%). The
      heterogeneity was found to be low (I=15%). This meta-analysis indicates a
      significantly higher risk for children born to HPV-positive mothers to become HPV
      positive themselves. Plausible explanations include vertical transmission of HPV
      during pregnancy and/or birth or a higher infection rate during early nursing
      from mother to child. More research is required to gain an insight into the
      precise mode of transmission and the clinical effects of infection on the child.

PMID- 22990005
TI  - High incidence of esophageal cancer in central-western Brazil: a migrant effect?
AB  - To determine the incidence and mortality rates of esophageal cancer in central
      western Brazil: Goiania, Brasilia, Cuiaba, and Campo Grande, incidence data for
      Cuiaba (2000-2005) and Brasilia (1999-2002) were obtained from the National
      Cancer Institute, and data from Goiania (1995-2008) from the Population-Based
      Cancer Registry of Goiania. Mortality data for the cities of central-western
      Brazil were obtained for the period 1980-2008 from the Ministry of Health. Age
      standardized incidence and mortality rates were calculated using the world
      population of Segi. Mortality trends were assessed with the Joinpoint Regression
      Program and a P value less than 0.05 was defined as significant. The highest
      incidence of esophageal cancer among men was in Cuiaba (16.0/100 000); the lowest
      was in Goiania (6.5/100 000). Among women, the incidence rates were similar in
      Brasilia and Cuiaba, but in Goiania, the incidence declined. There was a
      significant increase in mortality among men in Cuiaba (2.4%, P=0.03) and Campo
      Grande (1.2%, P=0.05), and in women (1.6%, P=0.04) in Goiania. Mortality by age
      group increased significantly in Campo Grande by 1.9% for men aged at least 50
      years and in Goiania by 2.7% among women aged at least 50 years; the mortality
      decreased in Goiania by 2.2% for women aged less than 50 years. The incidence of
      esophageal cancer in Brasilia and Cuiaba was similar to that of southern Brazil
      in some periods. There was an increase in mortality trends for men in Cuiaba and
      Campo Grande, and for women in Goiania.

PMID- 22990006
TI  - CEBPA gene mutations in Egyptian acute myeloid leukemia patients: impact on
      prognosis.
AB  - AIM: To assess the prognostic role of myeloid transcription factor gene CEBPA
      (CCAAT/enhancer binding protein-alpha), a novel gene involved in leukemia in
      Egyptian adults AML. MATERIALS AND METHODS: Screening for CEBPA mutations was
      assessed using PCR-single-strand conformation polymorphism (PCR-SSCP) in
      pretreatment bone marrow samples from 55 newly diagnosed adult AML. RESULTS:
      CEBPA mutations were found in 11 (20%) of 55 AML patients. They had significantly
      higher hemoglobin (P = 0.037), and lower LDH (P = 0.003) levels when compared to
      those without. CEBPA mutations were frequently detected in M4 (45.5%) and M2
      (27.2%) subtypes, and significantly associated with normal karyotype (90.9%, P =
      0.007). We distinguished six cases with two different mutations or one homozygous
      mutation (CEBPA(double-mut)) as well as five cases with only one single
      heterozygous mutation (CEBPA(single-mut)). Patients with CEBPA mutations had
      significantly higher complete remission (P = 0.047), lower mortality (p = 0.047).
      Double CEBPA mutant cases showed longer disease free survival (DFS) and overall
      survival (OS) when compared to wild type CEBPA (for DFS; median = 27 versus 24
      months respectively; P = 0.009 and for OS; median = 28 versus 25 months
      respectively; p = 0.008). No significant differences were found between
      CEBPA(single-mut) cases and wild type cases regarding DFS and OS (for DFS; median
      = 13 versus 24 months respectively; P = 0.615 and for OS; median = 14 versus 25
      months respectively; P = 0.703). CONCLUSION: CEBPA mutation status is known to be
      a prognostic factor for favorable outcome in AML patients. CEBPA(double-mut) is
      associated with favorable DFS and OS. In contrast, CEBPA(single-mut) AMLs
      survival studies did not differ significantly with wild-type cases. These results
      demonstrate significant underlying heterogeneity within CEBPA mutation positive
      AML with prognostic relevance. Based on these findings, we propose that
      CEBPA(double-mut) should be clearly defined from CEBPA(single-mut) AML and
      considered as a separate entity in the classification of AML. Furthermore,
      incorporation of CEBPA mutation status into novel risk-adapted therapeutic
      strategies in Egypt will improve the currently disappointing cure rate of this
      group of patients.

PMID- 22990007
TI  - Radiotherapy for rhabdomyosarcoma: indications and outcome.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood.
      Improvements in the clinical outcomes of rhabdomyosarcoma have been secondary to
      the intensification and refinement of treatment investigated by the Intergroup
      Rhabdomyosarcoma Study Group. Advances in diagnostic imaging techniques have led
      to improvements in staging and contribute to precision in radiation field design.
      Radiation treatment has been integrated into the primary treatment of most
      patients with rhabdomyosarcoma. Each treatment site has special considerations
      with regards to prognosis, outcomes and potential morbidities that affect the
      choice of local therapy. Advanced radiotherapy techniques using conformal
      treatment with intensity-modulated radiotherapy and proton therapy are
      particularly advantageous for the treatment of sites close to critical
      structures, such as the head and neck and genitourinary system. Active
      investigation is underway to develop strategies to reduce the radiation dose and
      volume in an effort to minimise late toxicity and improve the therapeutic ratio.

PMID- 22990008
TI  - Electrical conductivity of synergistically hybridized nanocomposites based on
      graphite nanoplatelets and carbon nanotubes.
AB  - In this investigation, a recent model for assessing the electrical conductivity
      of nanocomposites comprising a single type of conductive nanofiller was expanded
      to cases with mixtures of nanofillers. The extended model considers electron
      tunneling as the effective mechanism for insulator-conductor transition. The
      model was validated with relevant experimental data based on a mono-nanofiller.
      Using the extended model, the effective electrical conductivity of a
      nanocomposite comprising both graphite nanoplatelets and carbon nanotubes was
      investigated. It was observed that the hybridized nanocomposites filled with a
      mixture of these conductive nanofillers attain, synergistically, enhanced
      electrical conductivities at lower volume fractions. The lower filler contents
      assist in preserving the intrinsic properties of the host polymer in support of
      several applications. It was also observed that the relative aspect ratios of the
      conductive fillers play significant roles on the electrical conductivity of the
      hybrid nanocomposite. Simulations revealed that, generally, the addition of
      minimal amounts of a higher aspect ratio auxiliary phase to a lower aspect ratio
      main phase enhances the electrical conductivity of the composite by orders of
      magnitude.

PMID- 22990009
TI  - Age changes of facial measurements in European young adult males: implications
      for the identification of the living.
AB  - Metric and morphological analyses of facial features are currently applied in
      cases of personal identification of the living on images acquired from video
      surveillance systems. However, facial assessment in the forensic context needs to
      be based on reliable comparative data for facial measurements. Facial changes in
      the age range of early adulthood (20-30 years) have been rarely described so far,
      although such knowledge would be beneficial for comparative personal
      identification on images. This study investigates changes in facial measurements
      in European males aged between 20 and 30 years in order to identify metric
      characters that can be used for personal identification in young adults. A sample
      of 404 males of European ancestry, aged between 20 and 30 years from Germany,
      Italy and Lithuania were recruited for this project. Fourteen facial measurements
      were taken and correlation coefficients were calculated for each cranial
      measurement with age. Only two measurements - labial width and physiognomic ear
      length - seem to change between 20 and 30 years with a positive statistically
      significant correlation (p<0.05). These results suggest caution for what may
      concern personal identification by assessment of ear and mouth morphology.

PMID- 22990010
TI  - Impact of bacterial colonization on exhaled inflammatory markers in wheezing
      preschool children.
AB  - Wheeze is a common symptom in preschool children. The role of bacteria,
      regulatory T (T(reg)) cells and their association with airway inflammation in
      preschool wheeze is largely unknown. We evaluated inflammatory markers in exhaled
      breath condensate (EBC), bacterial colonization and circulating T(reg) cells in
      preschool children with and without recurrent wheeze. We recruited 252 children
      (aged two to four years) with (N = 202) and without (N = 50) recurrent wheeze.
      EBC was collected using an efficient closed glass condenser. Inflammatory markers
      in EBC (Interleukin(IL)-2, IL-4, IL-8, IL-10, IL-13) were assessed using
      multiplex immunoassay. Nasal and throat swabs were analysed for presence of
      Streptococcus pneumoniae, Haemophilus (para)influenzae and Staphylococcus aureus.
      Proportions of T(reg) cells (CD4(+)CD25(high)CD127(-)) were quantified by flow
      cytometry. Recurrent wheezing children had elevated EBC levels of IL-2, IL-4, IL
      10 and IL-13 compared to non-wheezers (odds ratio (95% confidence interval): 1.67
      (1.23-2.27): 1.58 (1.15-2.18): 1.47 (1.14-1.90): 1.55 (1.16-2.06), p <0.05,
      respectively). Bacteria were frequently present in children with and without
      wheeze, with no difference in prevalence (16-52% versus 16-50%, respectively).
      Moreover, the proportion of T(reg) cells did not differ between both groups.
      Wheezing children with bacterial colonization did not significantly differ in
      exhaled levels of inflammatory markers or proportion of T(reg) cells compared to
      wheezing children without colonization. The analysis of EBC might serve as a
      helpful non-invasive tool to early assess airway inflammation in wheezing
      children. The various elevated exhaled inflammatory markers indicate increased
      airway inflammation in wheezing preschool children. In the presence of wheeze, we
      found no evidence for bacterial induced airway inflammation.

PMID- 22990011
TI  - Paucity of IL-21-producing CD4(+) T cells is associated with Th17 cell depletion
      in SIV infection of rhesus macaques.
AB  - IL-21 regulates Th17 cell homeostasis, enhances the differentiation of memory B
      cells and antibody-secreting plasma cells, and promotes the maintenance of CD8(+)
      T-cell responses. In this study, we investigated the phenotype, function, and
      frequency of blood and intestinal IL-21-producing cells in nonhuman primates that
      are hosts of progressive (rhesus macaques [RMs]) and nonprogressive (sooty
      mangabeys [SMs]) SIV infection. We found that, in both species, memory
      CD4(+)CD95(+)CCR6(-) T cells are the main IL-21 producers, and that only a small
      fraction of CD4(+)IL-21(+) T cells produce IL-17. During chronic SIV infection of
      RMs, CD4(+)IL-21(+) T cells were significantly depleted in both blood and rectal
      mucosa, with the extent of this depletion correlating with the loss of Th17
      cells. Furthermore, treatment with IL-21 increased the in vivo levels of Th17
      cells in SIV-infected RMs. In contrast, normal levels of CD4(+)IL-21(+) T cells
      were found in SIV-infected SMs. Collectively, these data indicate that depletion
      of IL-21-producing CD4(+) T cells distinguishes progressive from nonprogressive
      SIV infection of RMs and SMs, and suggest that depletion of CD4(+)IL-21(+) T
      cells is involved in the preferential loss of Th17 cells that is associated with
      SIV disease progression. Further preclinical studies of IL-21 as a potential
      immunotherapeutic agent for HIV infection may be warranted.

PMID- 22990012
TI  - Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden
      distinguish progressive and nonprogressive lentiviral infections.
AB  - Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop
      a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain
      the nonprogressive nature of SIV infection in natural hosts that underlie
      maintained high levels of plasma viremia without apparent loss of target cells
      remain unclear. Here we used comprehensive approaches (ie, FACS sorting,
      quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study
      viral infection within subsets of peripheral blood and lymphoid tissue (LT)
      CD4(+) T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV
      infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1)
      infection frequencies among CD4(+) T cells in chronically SIV-infected RMs are
      significantly higher than those in SIVsmm-infected SMs; (2) infected cells are
      found in distinct anatomic LT niches and different CD4(+) T-cell subsets in SIV
      infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in
      humans; (3) T(FH) cells are infected at higher frequencies in RMs and humans than
      in SMs; and (4) LT viral burden, including follicular dendritic cell deposition
      of virus, is increased in RMs and humans compared with SMs. These data provide
      insights into how natural hosts are able to maintain high levels of plasma
      viremia while avoiding development of immunodeficiency.

PMID- 22990013
TI  - Engulfment of hematopoietic stem cells caused by down-regulation of CD47 is
      critical in the pathogenesis of hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is characterized by deregulated
      engulfment of hematopoietic stem cells (HSCs) by BM macrophages, which are
      activated presumably by systemic inflammatory hypercytokinemia. In the present
      study, we show that the pathogenesis of HLH involves impairment of the
      antiphagocytic system operated by an interaction between surface CD47 and signal
      regulatory protein alpha (SIRPA). In HLH patients, changes in expression levels
      and HLH-specific polymorphism of SIRPA were not found. In contrast, the
      expression of surface CD47 was down-regulated specifically in HSCs in association
      with exacerbation of HLH, but not in healthy subjects. The number of BM HSCs in
      HLH patients was reduced to approximately 20% of that of healthy controls and
      macrophages from normal donors aggressively engulfed HSCs purified from HLH
      patients, but not those from healthy controls in vitro. Furthermore, in response
      to inflammatory cytokines, normal HSCs, but not progenitors or mature blood
      cells, down-regulated CD47 sufficiently to be engulfed by macrophages. The
      expression of prophagocytic calreticulin was kept suppressed at the HSC stage in
      both HLH patients and healthy controls, even in the presence of inflammatory
      cytokines. These data suggest that the CD47-SIRPA antiphagocytic system plays a
      key role in the maintenance of HSCs and that its disruption by HSC-specific CD47
      down-regulation might be critical for HLH development.

PMID- 22990014
TI  - Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe
      hemochromatosis.
AB  - The deficiency of hepcidin, the hormone that controls iron absorption and its
      tissue distribution, is the cause of iron overload in nearly all forms of
      hereditary hemochromatosis and in untransfused iron-loading anemias. In a recent
      study, we reported the development of minihepcidins, small drug-like hepcidin
      agonists. Here we explore the feasibility of using minihepcidins for the
      prevention and treatment of iron overload in hepcidin-deficient mice. An
      optimized minihepcidin (PR65) was developed that had superior potency and
      duration of action compared with natural hepcidin or other minihepcidins, and
      favorable cost of synthesis. PR65 was administered by subcutaneous injection
      daily for 2 weeks to iron-depleted or iron-loaded hepcidin knockout mice. PR65
      administration to iron-depleted mice prevented liver iron loading, decreased
      heart iron levels, and caused the expected iron retention in the spleen and
      duodenum. At high doses, PR65 treatment also caused anemia because of profound
      iron restriction. PR65 administration to hepcidin knockout mice with pre-existing
      iron overload had a more moderate effect and caused partial redistribution of
      iron from the liver to the spleen. Our study demonstrates that minihepcidins
      could be beneficial in iron overload disorders either used alone for prevention
      or possibly as adjunctive therapy with phlebotomy or chelation.

PMID- 22990015
TI  - A genome-wide association study identifies a gene network of ADAMTS genes in the
      predisposition to pediatric stroke.
AB  - Pediatric stroke is a rare but highly penetrant disease with a strong genetic
      background. Although there are an increasing number of genome-wide association
      studies (GWASs) for stroke in adults, such studies for stroke of pediatric onset
      are lacking. Here we report the results of the first GWAS on pediatric stroke
      using a large cohort of 270 family-based trios. GWAS was performed using the
      Illumina 370 CNV single nucleotide polymorphisms array and analyzed using the
      transmission disequilibrium test as implemented in PLINK. An enrichment analysis
      was performed to identify additional true association signals among lower P value
      signals and searched for cumulatively associated genes within protein interaction
      data using dmGWAS. We observed clustering of association signals in 4 genes
      belonging to one family of metalloproteinases at high (ADAMTS12, P = 2.9 * 10(
      6); ADAMTS2, P = 8.0 * 10(-6)) and moderate (ADAMTS13, P = 9.3 * 10(-4);
      ADAMTS17, P = 8.5 * 10(-4)) significance levels. Over-representation and gene
      network analyses highlight the importance of the extracellular matrix in
      conjunction with members of the phosphoinositide and calcium signaling pathways
      in the susceptibility for pediatric stroke. Associated extracellular matrix
      components, such as ADAMTS proteins, in combination with misbalanced coagulation
      signals as unveiled by gene network analysis suggest a major role of postnatal
      vascular injury with subsequent thrombus formation as the leading cause of
      pediatric stroke.

PMID- 22990016
TI  - Flt3 inhibitor AC220 is a potent therapy in a mouse model of myeloproliferative
      disease driven by enhanced wild-type Flt3 signaling.
AB  - High levels of expression of wild-type Flt3 characterize many hematopoietic
      proliferative diseases and neoplasms, providing a potential therapeutic target.
      Using the c-Cbl RING finger mutant mouse as a model of a myeloproliferative
      disease (MPD) driven by wild-type Flt3, in the present study, we show that
      treatment with the Flt3 kinase inhibitor AC220 blocks MPD development by
      targeting Flt3(+) multipotent progenitors (MPPs). We found that daily
      administration of AC220 caused a marked reduction in Flt3 expression, induction
      of quiescence, and a significant loss of MPPs within 4 days. Unexpectedly, a
      robust Flt3 ligand-associated proliferative recovery response soon followed,
      preventing further loss of MPPs. However, continued AC220 treatment limited MPP
      recovery and maintained reduced, steady-state levels of cycling MPPs that express
      low levels of Flt3. Therefore, a finely tuned balance between the opposing forces
      of AC220 and Flt3 ligand production was established; whereas the Flt3 ligand
      blunted the inhibitory effects of AC220, the disease was held in remission for as
      long as therapy was continued. The net effect is a potent therapy indicating that
      patients with c-Cbl mutations, or those with similarly enhanced Flt3 signaling,
      may respond well to AC220 even after the induction of high levels of Flt3 ligand.

PMID- 22990017
TI  - The homeodomain region controls the phenotype of HOX-induced murine leukemia.
AB  - HOX proteins are widely involved in hematopoietic development. These
      transcription factors combine a conserved DNA-binding homeobox with a divergent N
      terminus that mediates interaction with variable cofactors. The resulting
      combinatorial diversity is thought to be responsible for mammalian HOX
      specificity. Contrasting this proposed mechanism for normal HOX function, here we
      demonstrate that, in the context of hematopoietic immortalization and
      leukemogenesis, individual HOX properties are governed almost exclusively by the
      homeodomain. Swap experiments between HOXA1 and HOXA9, 2 members of nonrelated
      paralog groups, revealed that gene expression patterns of HOX transformed cells
      in vitro are determined by the nature of the homeodomain. Similar results were
      seen in vivo during HOX-mediated leukemogenesis. An exchange of the homeodomains
      was sufficient to convert the slow, low-penetrance phenotype of HOXA1-induced
      leukemia to the aggressive fast-acting disease elicited by HOXA9 and vice versa.
      Mutation and deletion studies identified several subregions within the DNA
      binding domain responsible for paralog specificity. Previously defined binding
      sites for PBX cofactors within the exchangeable, nonhomeobox segment were
      dispensable for in vitro oncogenic HOX activity but affected in vivo disease
      development. The transcriptional activator domain shared by HOXA1 and HOXA9 at
      the very N-terminus proved essential for all transformation.

PMID- 22990018
TI  - Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia:
      a systematic review and meta-analysis.
AB  - The 4Ts is a pretest clinical scoring system for heparin-induced thrombocytopenia
      (HIT). Although widely used in clinical practice, its predictive value for HIT in
      diverse settings and patient populations is unknown. We performed a systematic
      review and meta-analysis to estimate the predictive value of the 4Ts in patients
      with suspected HIT. We searched PubMed, Cochrane Database, and ISI Web of Science
      for studies that included patients with suspected HIT, who were evaluated by both
      the 4Ts and a reference standard against which the 4Ts could be compared. Quality
      of eligible studies was assessed by QUADAS-2 criteria. Thirteen studies,
      collectively involving 3068 patients, fulfilled eligibility criteria. A total of
      1712 (55.8%) patients were classified by 4Ts score as having a low probability of
      HIT. The negative predictive value of a low probability 4Ts score was 0.998 (95%
      CI, 0.970-1.000) and remained high irrespective of the party responsible for
      scoring, the prevalence of HIT, or the composition of the study population. The
      positive predictive value of an intermediate and high probability 4Ts score was
      0.14 (0.09-0.22) and 0.64 (0.40-0.82), respectively. A low probability 4Ts score
      appears to be a robust means of excluding HIT. Patients with intermediate and
      high probability scores require further evaluation.

PMID- 22990019
TI  - Small nucleolar RNA expression profiling identifies potential prognostic markers
      in peripheral T-cell lymphoma.
AB  - Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous type of non-Hodgkin
      lymphoma (NHL) that, in general, is associated with a poor clinical outcome.
      Therefore, a current major challenge is the discovery of new prognostic tools for
      this disease. In the present study, a cohort of 122 patients with PTCL was
      collected from a multicentric T-cell lymphoma consortium (TENOMIC). We analyzed
      the expression of 80 small nucleolar RNAs (snoRNAs) using high-throughput
      quantitative PCR. We demonstrate that snoRNA expression analysis may be useful in
      both the diagnosis of some subtypes of PTCL and the prognostication of both PTCL
      not otherwise specified (PTCL-NOS; n = 26) and angio-immunoblastic T-cell
      lymphoma (AITL; n = 46) patients treated with chemotherapy. Like miRNAs, snoRNAs
      are globally down-regulated in tumor cells compared with their normal
      counterparts. In the present study, the snoRNA signature was robust enough to
      differentiate anaplastic large cell lymphoma (n = 32) from other PTCLs. For PTCL
      NOS and AITL, we obtained 2 distinct prognostic signatures with a reduced set of
      3 genes. Of particular interest was the prognostic value of HBII-239 snoRNA,
      which was significantly over-expressed in cases of AITL and PTCL-NOS that had
      favorable outcomes. Our results suggest that snoRNA expression profiles may have
      a diagnostic and prognostic significance for PTCL, offering new tools for patient
      care and follow-up.

PMID- 22990021
TI  - Perfluorooctane sulfonate-induced apoptosis of cerebellar granule cells is
      mediated by ERK 1/2 pathway.
AB  - Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is
      considered as a neurotoxicant to mammalian species. However, the underlying
      mechanism of its neurotoxicity is largely unknown. In the present study, we
      examined roles of mitogen-activated protein kinases (MAPKs) in PFOS-induced
      apoptosis of neuronal cells to elucidate the molecular mechanism. Cerebellar
      granule cells were isolated from 7-d old rats and maintained in culture for
      additional 7 d. Cells were exposed to PFOS and caspase-3 activity and nuclear
      morphology were evaluated by enzyme activity assay and Hoechst 33342 staining,
      respectively, to determine its effects on apoptosis. The treatment with PFOS
      resulted in caspase-3 activation and nuclear condensation and fragmentation. PFOS
      exposure selectively increased activation of ERK that remained above control over
      6 h. The inhibitor of ERK pathway, PD98059, substantially blocked caspase-3
      activation induced by PFOS, whereas inhibitors of JNK and p38 MAPK, SP600125 and
      SB203580, respectively, had no effect. PKC inhibitors, bisindolylmaleimide I and
      Go6976, dampened caspase-3 activity and ERK activation induced by PFOS.
      Collectively, it is suggested that PKC and ERK play proapoptotic roles in PFOS
      induced apoptosis of cerebellar granule cells and PKC act as an upstream
      regulator of ERK activation.

PMID- 22990022
TI  - Bioaccumulation of Cd, Pb and Zn in the edible and inedible tissues of three
      sturgeon species in the Iranian coastline of the Caspian Sea.
AB  - The accumulations of Cd, Pb and Zn were determined in edible and inedible tissues
      of Persian sturgeon (Acipenser persicus; n=27), stellate sturgeon (Acipenser
      stellatus; n=5) and beluga (Huso huso; n=4) collected from coastal waters of the
      South Caspian Sea from March to April 2011. Concentrations of metals evaluated in
      the caviar, muscle, liver, kidney, gills, ovary and heart of the three species of
      sturgeons have been assessed using the flame and graphite furnace atomic
      absorption spectrophotometer. Concentrations of Zn, Pb and Cd in the edible and
      inedible tissues were apparently different among the three species of sturgeons.
      Especially, beluga heart showed the highest concentrations of Zn and Pb and Cd in
      Persian sturgeon liver. The analyzed metals were found in the caviar and muscle
      samples of Persian sturgeon and likewise muscle samples two other sturgeon
      species at mean concentrations under the permissible limits proposed by MAFF
      (2000).

PMID- 22990023
TI  - Concentrations of perfluoroalkyl compounds in maternal and umbilical cord sera
      and birth outcomes in Korea.
AB  - This study analyzed the concentrations of perfluorooctane sulfonate (PFOS),
      perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) in maternal
      and umbilical cord sera at delivery from the general population in Korea. Seventy
      samples were analyzed with ion-pairing and LC/MS/MS. PFOS, PFOA and PFHxS were
      detected in both maternal and umbilical cord sera. There was a high correlation
      of PFC concentrations between maternal and cord serum samples, implying
      transplacental transport. Ranking of transplacental transfer efficiency was
      PFOA>PFHxS>PFOS. Student's t-tests revealed that concentrations of maternal PFOA
      were related with decreases in birth weight, birth length and ponderal index,
      suggesting a possible impact on fetal growth. With multiple logistic regression
      models, maternal PFOS concentration showed a significant inverse association with
      ponderal index (OR=0.22; 95% CI, 0.05-0.90). Umbilical cord PFHxS concentration
      showed a significant inverse association with birth weight (OR=0.26; 95% CI, 0.08
      0.85) or a marginally significant inverse association with birth length (OR=0.33;
      95% CI, 0.09-1.17). This is the first report demonstrating an inverse association
      of birth outcomes with PFHxS exposure. Concentrations of maternal PFOA were
      decreased with parity, implying that delivery is one of the major routes for PFOA
      elimination in women. This study demonstrated prenatal exposure of PFCs through
      placental transfer which could result in possible developmental effects in the
      population sampled. Our results may provide data basis to conduct a larger scale
      investigation into developmental effects of PFCs in the future and contribute to
      understanding levels of PFC contaminations from a variety of populations in the
      globe.

PMID- 22990024
TI  - Role of EDTA in arsenic mobilization and its uptake by maize grown on an As
      polluted soil.
AB  - EDTA amendments are widely used for micronutrient fertilization in arid soils,
      besides their effectiveness in the remediation process of heavy metal from
      contaminated soils. However, the persistence of EDTA in arsenic contaminated soil
      may have further negative effects on the grown plants. To investigate the
      influences of EDTA on soil As, a pot experiment was conducted using a sandy clay
      loam As-polluted soil treated with gradual rates of EDTA (0, 1.0, 2.5 and 5 mmol
      kg(-1)) and planted with maize for two months. The key findings reveal that EDTA
      applications increased AB-DTPA extractable and water soluble As significantly.
      Such increases seemed to be the main reasons behind the increase in As uptake by
      maize plants as the addition of EDTA at the rates of 1.0, 2.5 and 5.0 mmol kg(-1)
      increased significantly As uptake by shoots 1.5, 2.4 and 3.0 folds, respectively
      compared to the untreated soil. On the other hand, As uptake by roots did not
      increase significantly except with the highest application rates of 2.5 and 5.0
      mmol kg(-1). The results also show that arsenic translocation factor (TF) values
      were too low to attain successful phytoextraction. In conclusion, the
      bioavailable fraction of As is important to investigate the phytoextraction and
      phytotoxicity of As.

PMID- 22990025
TI  - Expression of Agrobacterium tumefaciens octopine Ti-plasmid virB8 gene is
      regulated by translational coupling.
AB  - Eleven proteins of the Agrobacterium tumefaciens virB operon are required for
      type IV secretion. All octopine Ti-plasmid pTiA6NC VirB proteins, except VirB8,
      could be expressed from a cloned monocistronic gene. Accumulation of VirB8
      required translation of the upstream virB7 gene. Analysis of chimeric virB8 genes
      and a newly constructed virB7 deletion mutant Agrobacterium AD1275 showed that
      translation of virB7, and not the gene product, is required for VirB8
      accumulation. Agrobacterium AD1275 accumulated VirB8 and other downstream virB
      gene products, and could be complemented with only virB7 in trans. In
      monocistronic virB8, sequences upstream of the virB8 ORF negatively controls
      virB8 expression possibly through the formation of a secondary structure that
      occludes both the ribosome binding site and translation start codon. Disruption
      of the structure through translation of the upstream gene ensures efficient
      translation of the virB8 mRNA in wild type bacteria. The pTiA6NC virB8 contains
      two potential translation start sites within the first eight codons. We show that
      the first AUG is used for virB8 translation initiation. The seven N-terminal
      residues resulting from translation initiation at the first AUG are required for
      both tumor formation and stabilization of VirB3. VirB8 and VirB4 are sufficient
      for the stabilization of VirB3, and VirB7 stabilizes VirB3 indirectly through its
      effect on virB8 expression.

PMID- 22990026
TI  - Helping primary care teams emerge through a quality improvement program.
AB  - BACKGROUND: Approaches to improving the quality of health care recognize the need
      for systems and cultures that facilitate optimal care. Interpersonal
      relationships and dynamics are a key factor in transforming a system to one that
      can achieve quality. The Quality in Family Practice (QIFP) program encompasses
      clinical and practice management using a comprehensive tool of family practice
      indicators. OBJECTIVE: The objective of this study was to explore and describe
      the views of staff regarding changes in the clinical practice environment at two
      affiliated academic primary care clinics (comprising one Family Health Team, FHT)
      who participated in QIFP. METHODS: An FHT in Hamilton, Canada, worked through the
      quality tool in 2008/2009. A qualitative exploratory case study approach was
      employed to examine staff perceptions of the process of participating. Semi
      structured interviews were conducted in early 2010 with 43 FHT staff with
      representation from physicians, nurses, allied health professionals, support
      staff and managers. Interviews were audio-taped and transcribed verbatim. A
      modified template approach was used for coding, with a complexity theory
      perspective of analysis. RESULTS: Themes included importance of leadership,
      changes to practice environment, changes to communication, an increased
      understanding of team roles and relationships, strengthened teamwork, flattening
      of hierarchy through empowerment, changes in clinical care and clinical impacts,
      challenges and rewards and sustainability. CONCLUSION: The program resulted in
      perceived changes to relationships, teamwork and morale. Addressing issues of
      leadership, role clarity, empowerment, flattening of hierarchy and teamwork may
      go a long way in establishing and maintaining a quality culture.

PMID- 22990020
TI  - Genome-wide association study for circulating levels of PAI-1 provides novel
      insights into its regulation.
AB  - We conducted a genome-wide association study to identify novel associations
      between genetic variants and circulating plasminogen activator inhibitor-1 (PAI
      1) concentration, and examined functional implications of variants and genes that
      were discovered. A discovery meta-analysis was performed in 19 599 subjects,
      followed by replication analysis of genome-wide significant (P < 5 * 10(-8))
      single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further
      examined associations with type 2 diabetes and coronary artery disease, assessed
      the functional significance of the SNPs for gene expression in human tissues, and
      conducted RNA-silencing experiments for one novel association. We confirmed the
      association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1
      (7q22.1) and discovered genome-wide significant associations at 3 additional
      loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 * 10(
      10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 * 10(-8));
      and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 * 10(-8)).
      Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal
      association with type 2 diabetes and coronary artery disease at ARNTL (P < .05).
      Functional studies identified MUC3 as a candidate gene for the second association
      signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated
      with the expression of MUC3 were robustly associated with circulating levels of
      PAI-1.

PMID- 22990027
TI  - Diagnostic accuracy of urine dipstick testing in screening for microalbuminuria
      in type 2 diabetes: a cohort study in primary care.
AB  - BACKGROUND: Clinical guidelines recommend annual screening for microalbuminuria
      in diabetes. Detection of microalbuminuria is important because it is associated
      with increased morbidity and mortality. Dipstick tests for microalbuminuria may
      be convenient, but their accuracy is uncertain. OBJECTIVE: To assess the utility
      of urine dipstick testing for microalbuminuria in type 2 diabetes. METHODS: In a
      6-week cohort study in four general practices in Oxfordshire, UK, first-pass
      urine samples were obtained at two weekly intervals from patients with type 2
      diabetes and tested in the practice using Micral-Test and Microalbustix urine
      dipsticks. Parallel samples were sent for laboratory albumin-creatinine ratio
      (ACR) assay. Results of single dipstick tests and sequences of dipstick and
      laboratory tests were compared with a clinical testing strategy based on current
      guidelines to assess the accuracy and estimate costs of testing. RESULTS: The
      prevalence of microalbuminuria was 12.5% (n = 88). Mean (standard deviation) age
      was 68 (10) years, 56 (57%) were men. Median (interquartile range) diabetes
      duration was 6.2 (2.0-10.0) years. The sensitivity and specificity, respectively,
      of a single Micral-Test were 91.7% and 44.0% and of a Microalbustix test 33.3%
      and 92.0%. Testing strategies involving dipstick and laboratory ACR measurements
      or dipstick tests had similar accuracy. The costs of using dipstick tests were
      overall lower than laboratory ACR-based testing. CONCLUSIONS: Dipstick testing in
      this study did not reliably identify diabetes patients with microalbuminuria.
      Although dipstick testing would decrease testing costs, it could either fail to
      diagnose most patients with microalbuminuria or increase the numbers of patients
      retested depending on the dipstick used.

PMID- 22990028
TI  - Syphilis or jealousy? Analysis of a figure in Bronzino's painting 'Allegory of
      Venus and Cupid' (National Gallery, London).

PMID- 22990029
TI  - Pathogenicity of Bordetella avium under immunosuppression induced by
      Reticuloendotheliosis virus in specific-pathogen-free chickens.
AB  - Multiple infections of Bordetella avium (B. avium) with virus, especially
      immunosuppressive virus, have become more and more severe in chickens in China.
      The increasing morbidity and mortality of its complications have amplified
      concerns about the impact of B. avium on animal health. To evaluate the
      pathogenicity of B. avium under immunosuppression status, we developed four types
      of Reticuloendotheliosis virus (REV) infection models. After a comparison of body
      weight, relative immune organ index, Newcastle disease virus antibody titers and
      lymphocyte ratio, we chose the early age with low dose infection as our
      immunosuppressive model. To investigate the pathogenicity of B. avium under this
      model, a study was completed in which chickens were inoculated with REV-only, B.
      avium-only, both agents (REV -B. avium) or first inoculated with REV and 5 d
      later with B. avium (REV/B. avium). Results revealed that antibody titers to B.
      avium, concentrations of IFN-gamma and SIgA were decreased in coinfected chickens
      when compared to the B. avium-only chickens, but the changing trend was similar
      between REV/B. avium and B. avium-only groups. Overall, REV did enhance the
      pathogenicity of B. avium. However, B. avium-only did not cause severe immune
      dysfunction unless chicks were coinfected with REV. REV preceding infection with
      B. avium showed mild impairment, which needs further exploration.

PMID- 22990030
TI  - Weight loss and dropout during a commercial weight-loss program including a very
      low-calorie diet, a low-calorie diet, or restricted normal food: observational
      cohort study.
AB  - BACKGROUND: The effectiveness of commercial weight-loss programs consisting of
      very-low-calorie diets (VLCDs) and low-calorie diets (LCDs) is unclear.
      OBJECTIVE: The aim of the study was to quantify weight loss and dropout during a
      commercial weight-loss program in Sweden (Itrim; cost: $1300/?1000; all
      participants paid their own fee). DESIGN: This observational cohort study linked
      commercial weight-loss data with National Health Care Registers. Weight loss was
      induced with a 500-kcal liquid-formula VLCD [n = 3773; BMI (in kg/m(2)): 34 +/- 5
      (mean +/- SD); 80% women; 45 +/- 12 y of age (mean +/- SD)], a 1200-1500-kcal
      formula and food-combination LCD (n = 4588; BMI: 30 +/- 4; 86% women; 50 +/- 11 y
      of age), and a 1500-1800-kcal/d restricted normal-food diet (n = 676; BMI: 29 +/-
      5; 81% women; 51 +/- 12 y of age). Maintenance strategies included exercise and a
      calorie-restricted diet. Weight loss was analyzed by using an intention-to-treat
      analysis (baseline substitution). RESULTS: After 1 y, mean (+/-SD) weight changes
      were -11.4 +/- 9.1 kg with the VLCD (18% dropout), -6.8 +/- 6.4 kg with the LCD
      (23% dropout), and -5.1 +/- 5.9 kg with the restricted normal-food diet (26%
      dropout). In an adjusted analysis, the VLCD group lost 2.8 kg (95% CI: 2.5, 3.2)
      and 3.8 kg (95% CI: 3.2, 4.5) more than did the LCD and restricted normal-food
      groups, respectively. A high baseline BMI and rapid initial weight loss were both
      independently associated with greater 1-y weight loss (P < 0.001). Younger age
      and low initial weight loss predicted an increased dropout rate (P < 0.001).
      Treatment of depression (OR: 1.4; 95% CI: 1.1, 1.9) and psychosis (OR: 2.6; 95%
      CI: 1.1, 6.3) were associated with an increased dropout rate in the VLCD group.
      CONCLUSION: A commercial weight-loss program, particularly one using a VLCD, was
      effective at reducing body weight in self-selected, self-paying adults.

PMID- 22990031
TI  - The effect of prepubertal calcium carbonate supplementation on the age of peak
      height velocity in Gambian adolescents.
AB  - BACKGROUND: Limited evidence suggests that calcium intake before puberty
      influences adolescent height growth and the timing of puberty. Such an effect
      might be particularly marked in populations in whom low calcium intake, stunting,
      and delayed puberty are common. OBJECTIVE: The objective was to test whether 12
      mo of calcium supplementation at age 8-12 y to increase intakes toward
      international recommendations had long-term effects on adolescent growth and
      pubertal development in rural Gambian children. DESIGN: This was a longitudinal
      study of 160 Gambian boys (n = 80) and girls (n = 80) who had participated in a
      12-mo, randomized, double-blind, placebo-controlled, calcium carbonate
      supplementation trial (1000 mg Ca/d, 5 d/wk) at age 8-12 y. Anthropometric
      measures were made every 1-2 y until age 21-25 y; pubertal status and menarche
      data were collected. Repeated-measures ANCOVA and Superimposition by Translation
      and Rotation Method (SITAR) growth models were used to assess the effects of
      treatment. RESULTS: In boys, midadolescent height growth was advanced in the
      calcium group, which resulted in greater stature at a mean age of 15.5 y (mean +/
      SEM: 2.0 +/- 0.8 cm; P = 0.01) and an earlier age of peak height velocity by 7.4
      +/- 2.9 mo. Subsequently, the calcium group stopped growing earlier (P = 0.02)
      and was 3.5 +/- 1.1 cm shorter (P = 0.002) at a mean age of 23.5 y. Weight and
      midupper arm circumference paralleled height. No significant effects were
      observed in girls, but a sex-by-supplement interaction on height growth could not
      be confirmed. CONCLUSION: Calcium supplementation of boys in late childhood
      advanced the age of peak height velocity and resulted in shorter adult stature in
      a population in whom low calcium intakes and delayed puberty are common. This
      trial was registered at isrctn.org as ISRCTN28836000.

PMID- 22990032
TI  - Effects of trimming weight-for-height data on growth-chart percentiles.
AB  - BACKGROUND: Before estimating smoothed percentiles of weight-for-height and BMI
      for-age to construct the WHO growth charts, WHO excluded observations that were
      considered to represent unhealthy weights for height. OBJECTIVE: The objective
      was to estimate the effects of similar data trimming on empirical percentiles
      from the CDC growth-chart data set relative to the smoothed WHO percentiles for
      ages 24-59 mo. DESIGN: We used the nationally representative US weight and height
      data from 1971 to 1994, which was the source data for the 2000 CDC growth charts.
      Trimming cutoffs were calculated on the basis of weight-for-height for 9722
      children aged 24-71 mo. Empirical percentiles for 7315 children aged 24-59 mo
      were compared with the corresponding smoothed WHO percentiles. RESULTS: Before
      trimming, the mean empirical percentiles for weight-for-height in the CDC data
      set were higher than the corresponding smoothed WHO percentiles. After trimming,
      the mean empirical 95th and 97th percentiles of weight-for-height were lower than
      the WHO percentiles, and the proportion of children in the CDC data set above the
      WHO 95th percentile decreased from 7% to 5%. The findings were similar for BMI
      for-age. However, for weight-for-age, which had not been trimmed by the WHO, the
      empirical percentiles before trimming agreed closely with the upper percentiles
      from the WHO charts. CONCLUSION: WHO data-trimming procedures may account for
      some of the differences between the WHO growth charts and the 2000 CDC growth
      charts.

PMID- 22990033
TI  - Slowly and rapidly digestible starchy foods can elicit a similar glycemic
      response because of differential tissue glucose uptake in healthy men.
AB  - BACKGROUND: Previously we observed that the consumption of pasta and bread
      resulted in a similar glycemic response, despite a slower intestinal influx rate
      of glucose from the pasta. Underlying mechanisms of this effect were not clear.
      OBJECTIVE: The objective was to investigate the differences in glucose kinetics
      and hormonal response after consumption of products with slow and rapid in vivo
      starch digestibility but with a similar glycemic response. DESIGN: Ten healthy
      male volunteers participated in a crossover study and consumed (13)C-enriched
      wheat bread or pasta while receiving a primed-continuous D-[6,6-(2)H(2)]glucose
      infusion. The dual-isotope technique enabled calculation of the following glucose
      kinetics: rate of appearance of exogenous glucose (RaE), endogenous glucose
      production, and glucose clearance rate (GCR). In addition, postprandial plasma
      concentrations of glucose, insulin, glucagon, and glucose-dependent
      insulinotropic polypeptide (GIP) were analyzed. RESULTS: GIP concentrations after
      pasta consumption were lower than after bread consumption and strongly correlated
      with the RaE (r = 0.82, P < 0.01). The insulin response was also lower after
      pasta consumption (P < 0.01). In accordance with the low insulin response, the
      GCR was lower after pasta consumption, which explained the high glycemic response
      despite a low RaE. CONCLUSIONS: Slower intestinal uptake of glucose from a
      starchy food product can result in lower postprandial insulin and GIP
      concentrations, but not necessarily in a lower glycemic response, because of a
      slower GCR. Even without being able to reduce postprandial glycemia, products
      with slowly digestible starch can have beneficial long-term effects. These types
      of starchy products cannot be identified by using the glycemic index and
      therefore another classification system may be necessary. This trial was
      registered at controlled-trials.com as ISRCTN42106325.

PMID- 22990035
TI  - Use of intravenous fluids for the treatment of patients intoxicated with ethanol
      (alcohol):  is it a scientific-based practice?

PMID- 22990034
TI  - Regional brain response to visual food cues is a marker of satiety that predicts
      food choice.
AB  - BACKGROUND: Neuronal processes that underlie the subjective experience of satiety
      after a meal are not well defined. OBJECTIVE: We investigated how satiety alters
      the perception of and neural response to visual food cues. DESIGN: Normal-weight
      participants (10 men, 13 women) underwent 2 fMRI scans while viewing images of
      high-calorie food that was previously rated as incompatible with weight loss and
      "fattening" and low-calorie, "nonfattening" food. After a fasting fMRI scan,
      participants ate a standardized breakfast and underwent reimaging at a randomly
      assigned time 15-300 min after breakfast to vary the degree of satiety. Measures
      of subjective appetite, food appeal, and ad libitum food intake (measured after
      the second fMRI scan) were correlated with activation by "fattening" (compared
      with "nonfattening") food cues in a priori regions of interest. RESULTS: Greater
      hunger correlated with higher appeal ratings of "fattening" (r = 0.46, P = 0.03)
      but not "nonfattening" (r = -0.20, P = 0.37) foods. Fasting amygdalar activation
      was negatively associated with fullness (left: r = -0.52; right: r = -0.58; both
      P <= 0.01), whereas postbreakfast fullness was positively correlated with
      activation in the dorsal striatum (right: r = 0.44; left: r = 0.45; both P <
      0.05). After breakfast, participants with greater activation in 4 regions-medial
      orbital frontal cortex (r = 0.49, P < 0.05), left amygdala (r = 0.49, P < 0.05),
      left insula (r = 0.47, P < 0.05), and nucleus accumbens (right: r = 0.57, P <
      0.01; left: r = 0.43, P < 0.05)-chose buffet foods with higher fat content.
      CONCLUSIONS: Postmeal satiety is shown in regional brain activation by images of
      high-calorie foods. Regions including the amygdala, nucleus accumbens, and dorsal
      striatum may alter perception of, and reduce motivation to consume, energy-rich
      foods, ultimately driving food choice. This trial was registered at
      clinicaltrials.gov as NCT01631045.

PMID- 22990036
TI  - Calcium administration during cardiac arrest:  a systematic review.
AB  - This topic highlights the results of the literature review on calcium therapy
      during cardiac arrest and cardiopulmonary resuscitation according to the
      Patient/population, Intervention, Comparator, Outcome structure. Eligible studies
      were assigned to one of the five levels of evidence. Their quality was rated as
      either good, fair, or poor and then classified as supportive, neutral, or
      opposing according to the outcome benefits. Among the 48 articles retrieved, 10
      articles fulfilled all the criteria for analysis for the Guidelines preparation.
      There is no evidence that the administration of calcium during cardiopulmonary
      resuscitation improves survival from cardiac arrest irrespective of the
      presenting rhythm. In the setting of hyperkalemia, calcium channel blocker
      intoxication, hypocalcemia, and hypermagnesemia, the role of calcium remains
      unclear because of the limited amount of evidence. The main limitation is the
      scarcity of data, most of which relate to anoxic cardiac arrest, accounting for
      no more than 25% of the causes of cardiac arrest in humans.

PMID- 22990037
TI  - Reducing the potential for tourniquet-associated reperfusion injury.
AB  - OBJECTIVE: Investigate a strategy to minimize tourniquet-associated reperfusion
      injury. METHODS: Sixteen healthy patients scheduled for repair of bimalleolar
      ankle fractures were randomized into two groups. In the standard release group
      (R, n1=6), the tourniquet was fully deflated at the end of surgery. In the
      staggered release group (SR, n2=10), the tourniquet was fully deflated for 30 s
      and subsequently reinflated to 300 mmHg. The procedure was repeated twice at 3
      min intervals before complete removal. Haemodynamic and blood biochemistry
      measurements were obtained from an indwelling arterial catheter immediately
      before the initial tourniquet deflation and thereafter at 1, 4, 7 and 15 min.
      RESULTS: Serum Ca concentrations were less in group R at 4 min (1.027 +/- 0.5 vs.
      1.084 +/- 0.07 mmol/l, P=0.046) and 7 min (1.045 +/- 0.04 vs. 1.110 +/- 0.06
      mmol/l, P=0.013). The serum lactate concentration was higher in group R compared
      with group SR at 1 min (1.75 +/- 0.19 vs. 1.33 +/- 0.31 mmol/l, P=0.005) and 4
      min (1.98 +/- 0.23 vs. 1.48 +/- 0.39 mmol/l, P=0.007), respectively. End-tidal
      CO2 was less in group SR compared with group R at 1 min (4.82 +/- 0.45 vs. 5.68
      +/- 0.26 kPa, P=0.0004) and 4 min (5.01 +/- 0.59 vs. 5.68 +/- 0.35 kPa, P=0.01),
      respectively. At 15 min, less hypotension and bradycardia was noted in group SR.
      CONCLUSION: A staggered tourniquet release was associated with greater
      haemodynamic stability and reduced the rate of acute systemic metabolic changes
      associated with limb reperfusion. Reapplication of a tourniquet seemed to halt
      further reperfusion, providing a window period for patient evaluation and
      management.

PMID- 22990038
TI  - Research on teacher education programs: logic model approach.
AB  - Teacher education programs in the United States face increasing pressure to
      demonstrate their effectiveness through pupils' learning gains in classrooms
      where program graduates teach. The link between teacher candidates' learning in
      teacher education programs and pupils' learning in K-12 classrooms implicit in
      the policy discourse suggests a one-to-one correspondence. However, the logical
      steps leading from what teacher candidates have learned in their programs to what
      they are doing in classrooms that may contribute to their pupils' learning are
      anything but straightforward. In this paper, we argue that the logic model
      approach from scholarship on evaluation can enhance research on teacher education
      by making explicit the logical links between program processes and intended
      outcomes. We demonstrate the usefulness of the logic model approach through our
      own work on designing a longitudinal study that focuses on examining the process
      and impact of an undergraduate mathematics and science teacher education program.

PMID- 22990039
TI  - Levetiracetam-associated aggravation of myoclonic seizure in children.
AB  - Some antiepileptic drugs (AEDs) have been reported to aggravate generalized
      seizures. We have seen three children whose myoclonic seizures increased on
      starting treatment with Levetiracetam. In all seizures aggravation was temporally
      associated to the introduction of the drug. All became seizure-free on withdrawal
      of levetiracetam with a switch to an alternative antiepileptic drug and this
      persisted for at least 6 months. This suggests that some children with myoclonic
      seizures may have an aggravation on starting treatment with levetiracetam but
      this requires further studies.

PMID- 22990040
TI  - Infections with mimivirus in patients with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Antibodies against mimivirus, a recently discovered giant virus,
      have been found in patients presenting with pneumonia suggesting a potential role
      for this virus as a respiratory pathogen. Several bacterial and viral pathogens
      have been associated with the occurrence of acute exacerbations in COPD. However,
      a large part of these exacerbations have an unknown cause. In the present study
      we evaluated the presence of mimivirus in sputum samples of COPD patients.
      METHODS: From March 2009 until January 2010 all sputum samples collected during
      stable conditions and during exacerbations of COPD patients, referred for
      pulmonary rehabilitation, were included. All sputum samples were analysed by real
      time PCR targeting mimivirus. Furthermore, serum samples were analysed for the
      presence of antibodies against mimivirus. RESULTS: A total of 220 sputum samples
      from 109 patients were eligible for inclusion. None of the sputum samples showed
      the presence of mimivirus DNA. Antibodies against mimivirus were detected in 3
      serum samples from 3 patients, of which one showed an increase in antibody-titre.
      CONCLUSIONS: Although mimivirus was suggested as a potential respiratory
      pathogen, its presence could not be confirmed in the present study-population of
      patients with COPD.

PMID- 22990041
TI  - Asthma controller delay and recurrence risk after an emergency department visit
      or hospitalization.
AB  - BACKGROUND: Patients who have asthma-related emergency department (ED) visits or
      hospitalizations are at risk for recurrent exacerbation events. Our objectives
      were to assess whether receiving a controller medication at discharge affects
      risk of recurrence and whether delaying controller initiation alters this risk.
      METHODS: Asthma patients with an ED visit or inpatient (IP) stay who received a
      controller dispensing within 6 months were identified from healthcare claims. Cox
      proportional hazards of the time to first recurrence of an asthma-related ED or
      IP visit in the 6-month period following the initial event were constructed, with
      time following discharge without controller medication as the primary predictor.
      RESULTS: A total of 6139 patients met inclusion criteria, 78% with an ED visit
      and 22% with an IP visit; 15% had a recurrence within 6 months. The adjusted
      hazard ratio (HR) associated with not having controller medication at discharge
      was 1.79 (95% confidence interval [CI], 1.42-2.25). The controller-by-time
      interaction was significant (P<0.001), with hazard rising as time-to-controller
      initiation increased. Delaying initiation by 1 day approximately tripled the risk
      (HR 2.95; 95%CI 1.48-5.88). Sensitivity analyses, including accounting for
      controller fills prior to the index event, did not substantially alter these
      results. CONCLUSIONS: This observational study shows that the risk of a recurrent
      asthma-related ED visit or IP stay increased as the time to initiate a controller
      increased. Our findings support the importance of early controller initiation
      following an asthma-related ED or IP visit in reducing risk of recurrence.

PMID- 22990042
TI  - Diagnosis according to World Health Organization determines the long-term
      prognosis in patients with myeloproliferative neoplasms treated with anagrelide:
      results of a prospective long-term follow-up.
AB  - OBJECTIVES: During long term follow-up of a cohort of patients with essential
      thrombocythemia (ET) and polycythemia vera (PV) a higher than expected incidence
      of myelofibrosis (MF) was noted. In order to test if the explanation could be
      found in the diagnostic criteria a re-evaluation  of diagnosis using the 2008 WHO
      diagnostic criteria for ET and MF was performed. METHODS: This prospective study
      of 60 patients with ET and PV was set up in 1998 to evaluate the long-term
      efficacy and tolerability of anagrelide treatment. Bone marrow trephine biopsies
      were  requested from study start, after 2 and 7 years of follow-up. A blinded re
      evaluation of the bone marrow trephines was performed. The 2008 WHO bone marrow
      criteria were used for diagnosis and fibrosis grading. RESULTS: Of 40 patients
      with an initial diagnosis of ET, 21 were  confirmed as 'true ET' whereas 17 were
      reclassified as primary myelofibrosis (PMF) (12 PMF-0, 3 PMF-1, 2 PMF-2) and 2 as
      myeloproliferative neoplasms of uncertain origin. After 7 years of follow-up, 19
      of 21 patients with 'true ET' were alive, none had transformed to  MF, leukemia,
      or myelodysplastic syndrome. In contrast, 4/17 patients reclassified as PMF had
      died, two patients transformed to myelodysplastic syndrome and 7 patients
      progressed to overt MF. DISCUSSION: We conclude that a blinded re-evaluation of
      bone marrow trephines from  study start and after 7 years of follow-up using 2008
      World Health Organization criteria was able to differentiate between true ET and
      PMF with a marked difference in follow-up outcome.

PMID- 22990043
TI  - Niacin administration significantly reduces oxidative stress in patients with
      hypercholesterolemia and low levels of high-density lipoprotein cholesterol.
AB  - Oxidative stress has been implicated in the pathogenesis of cardiovascular
      disorders, including atherosclerosis. In pharmacological doses, niacin (vitamin
      B3) was proven to reduce total cholesterol, triglyceride, very-low-density
      lipoprotein, and low-density lipoprotein levels, and to increase high-density
      lipoprotein (HDL) levels. The aim of this study was to evaluate the effect of
      niacin treatment in patients with low levels of HDL cholesterol (HDL-C; <40 mg%)
      on their lipid profile and oxidative stress status. Seventeen patients with
      hypercholesterolemia and low HDL-C and 8 healthy control subjects were enrolled
      in the study. The patients were treated with niacin for 12 weeks. Lipid profile,
      oxidative stress and C-reactive protein (CRP) levels were determined at the time
      of enrollment, and 2 and 12 weeks after initiation of niacin treatment. Subjects
      with lower HDL-C levels exhibited higher oxidative stress compared with subjects
      with normal HDL-C levels. Niacin treatment in hypercholesterolemic patients
      caused a significant increase in HDL-C and apolipoprotein A1 levels, and a
      decrease in triglyceride levels. Niacin also significantly reduced oxidative
      stress, as measured by a significant decrease in the serum content of
      thiobarbituric acid reactive substances, lipid peroxides and paraoxonase
      activity, compared with the levels before treatment. Although serum CRP levels
      were not affected by niacin treatment, a correlation between CRP and HDL levels
      was obtained when computing the results. Niacin treatment in hypercholesterolemic
      patients with low HDL levels caused a significant decrease in their oxidative
      stress status. These results indicate an additional beneficial effect of niacin
      beyond its ability to affect the lipid profile.

PMID- 22990044
TI  - Relationship between psychiatric disorders and quality of life in nondialysis
      patients with chronic kidney disease.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      psychiatric disorders (anxiety and depression) and quality of life (QOL) in
      nondialysis patients with chronic kidney disease (CKD). METHODS: QOL was
      evaluated in a sample of 57 nondialysis patients with CKD using the 36-item Short
      Form Health Survey questionnaire comprising 8 scales, including the physical
      component summary and mental component summary measures. Depression and anxiety
      were estimated using the Hamilton Depression Rating Scale and Hamilton Anxiety
      Rating Scale, respectively. RESULTS: Depression and anxiety scores were
      negatively correlated with 7 of the 8 scales of the Short Form 36 questionnaire,
      and with the physical component summary and mental component summary scores,
      despite 38.6% patients with depression and 54.4% with anxiety, whereas QOL in the
      depression group, the anxiety group, and the anxiety and depression comorbid
      group was lower than that for those without the corresponding psychiatric
      disorders (P < 0.05). CONCLUSIONS: This study demonstrates that depression and
      anxiety, commonly encountered in patients with CKD, could be a risk factor for
      QOL in these patients.

PMID- 22990045
TI  - Capnocytophaga canimorsus sepsis with associated thrombotic thrombocytopenic
      purpura.
AB  - Capnocytophaga canimorsus, a bacterium commonly transmitted via dog bites, is
      known to cause sepsis in immunocompromised patients. Thrombotic thrombocytopenic
      purpura and hemolytic uremic syndrome are rare complications of infection. The
      authors present a case of C canimorsus sepsis and thrombotic thrombocytopenic
      purpura in an asplenic patient and review the relevant literature.

PMID- 22990046
TI  - Selenium and cardiometabolic health: inconclusive yet intriguing evidence.
AB  - Selenium is incorporated as the unique amino acid selenocysteine into
      selenoproteins, which regulate important biologic processes such as redox
      balance. The results of epidemiologic and clinical investigations are
      inconclusive regarding the relation of the plasma selenium level to
      cardiometabolic parameters and does not support the routine use of selenium
      supplements to prevent cancer or cardiovascular disease. Variability in the
      selenium status of the populations studied and lack of standardization of
      measures of selenium status may account for part of the confusion regarding
      selenium and cardiometabolic health. Another possibility is that differences in
      the effects of selenoproteins, as opposed to those of low-molecular-weight
      selenium compounds derived from in vivo metabolism of selenium, may explain the
      unusual phenomenon of a similar phenotype induced by both selenium deficiency and
      excess in experimental models and offer a plausible explanation for the lack of
      consistency in clinical studies. The epidemiologic, clinical, and experimental
      evidence, although inconclusive in terms of the precise relation of selenium to
      cardiometabolic health, is however very intriguing in terms of the urgent need
      for further mechanistic research to enable the clinical use of this potent
      micronutrient.

PMID- 22990047
TI  - Angiokeratomas in Fabry disease.

PMID- 22990049
TI  - Parasitic diseases of the pleura.
AB  - Parasitic infections are prevalent in certain parts of the world and may cause
      pleural involvement, which often goes unrecognized. Common parasites involving
      the pleura include Entamoeba histolytica, Echinococcus granulosus and Paragonimus
      westermani. Amebiasis can cause empyema with "anchovy sauce" pus, reactive
      pleural effusions and bronchopleural fistula with hydropneumothorax.
      Echinococcosis may result in pleural thickening, pneumothorax, secondary pleural
      hydatidosis and pleural effusions. Paragonimiasis may cause chylous and
      cholesterol pleural effusions, pleural thickening and pneumothorax. Less
      commonly, pulmonary eosinophilia, or Loeffler's syndrome, caused by Ascaris
      lumbricoides, Ancylostoma duodenale and Necator americanus and tropical pulmonary
      eosinophilia caused by Wuchereria bancrofti and Brugia malayi may involve the
      pleura. This article provides a comprehensive review of parasitic infections
      involving the pleura. A high index of suspicion in the appropriate clinical
      setting is required to facilitate prompt diagnosis and treatment of these
      diseases.

PMID- 22990048
TI  - Orofacial manifestations in patients with sickle cell disease.
AB  - BACKGROUND: The aim of this study was to review the orofacial manifestations in
      patients with sickle cell disease (SCD). METHODS: Indexed databases were explored
      using various combinations of the following keywords: "sickle cell anemia,"
      "sickle cell disease," "oral health status" and "dental inflammation." RESULTS:
      Hypoxia has been associated with osteomyelitis of the jaws, particularly the
      mandible in patients with SCD. Bone marrow hyperplasia in these patients causes
      depression of nasal bridge, midfacial overgrowth and malocclusion. Mental nerve
      neuropathy due to osteomyelitis of the mandible causes numbness in the lower lip
      and chin. A diminished blood supply to teeth causes necrosis of the dental pulp
      in patients with SCD. Dental caries is a common manifestation in patients with
      SCD, particularly in those with underprivileged living standards. The association
      between SCD and periodontal inflammatory conditions remains unclear. CONCLUSIONS:
      Oral health problems in patients with SCD are rare and occur mainly as a result
      of the poor oral hygiene maintenance.

PMID- 22990050
TI  - In situ synchrotron study of Au-Pd nanoporous alloy formation by single-source
      precursor thermolysis.
AB  - We have successfully prepared a face-centered cubic Au-Pd nanoporous structure
      (NPS) in a one-pot reaction under thermal decomposition of single-source
      precursor [Pd(NH(3))(4)][AuCl(4)](2). The precursor employed contains both
      desired metals 'mixed' on the molecular level, thus providing its significant
      advantages for obtaining alloys. The observation using a high-resolution
      transmission electron microscope has shown that the nanostructure was composed of
      interconnected polycrystalline ligaments with an average diameter of 14 +/- 3 nm.
      The measurements made by energy-dispersive x-ray analysis and powder x-ray
      diffraction (XRD) confirm that the nanostructure consists of Au(0.67)Pd(0.33)
      alloy. In situ real-time synchrotron XRD was used to study the formation
      mechanism for Au-Pd alloy NPS. We provide the correlation of control parameters
      (such as temperature, rate of increase of temperature and gas atmosphere) with
      the microstructure and phase behavior of bimetallic products. Under reducing
      conditions (H(2) atmosphere) the first step is the formation of alloy nanowires.
      Finally, bimetallic alloy 3D nanostructure is formed after the complete
      decomposition of the precursor (100  degrees C).

PMID- 22990051
TI  - Soluble inflammation markers in nasal lavage from CF patients and healthy
      controls.
AB  - BACKGROUND: CF sinonasal and bronchial mucosa reveal identical ion channel
      defects. Nasal Lavage (NL) allows non-invasive repeated sampling of airway
      surface liquid. We compared inflammatory mediators in NL from CF-patients and
      healthy controls, and in CF in relation to sinonasal pathogen colonization.
      METHODS: From 40 CF-patients (mean age 21.8yrs, SD 11.8yrs.) and 52 healthy
      controls (mean age 31.9yrs., SD 13.7yrs.) NL-fluid (10ml/nostril) concentrations
      of MPO, IL-8, IL-17A, sICAM-1, IL-1beta, IL-6, TNF-alpha, IL-10 and IL-5 were
      determined using cytometric bead arrays for flow cytometry. RESULTS: CF-patients
      showed significantly higher MPO-concentrations in NL-fluid and higher IL-8-levels
      (n.s.) than controls. MPO, IL-8, IL-17A, sICAM-1, IL-1beta and IL-6 were
      significantly more often detectable in CF-patients than in controls. CF-patients
      with S. aureus colonization in both upper and lower airways had significantly
      elevated MPO and IL-8 levels in NL-fluid compared to S. aureus negatives.
      CONCLUSION: NL-fluid differed substantially between CF-patients and healthy
      controls with most promising results for IL-8 and MPO, a primarily in CF-NL
      assessed mediator. Further studies are required to assess effects of sample
      collection and processing on concentrations of inflammatory markers and to
      evaluate potentials of NL analysis in research and clinical routine.

PMID- 22990052
TI  - Crystallite size--is it a new predictor for renal stone burden?
AB  - OBJECTIVE: To evaluate the importance of stone composition and crystallite size
      in the formation of ultimate stone burden. Crystallite is the smallest building
      block, which is unique in size and architecture for each type of stone component.
      Currently, the knowledge about the clinical importance of crystallite size is
      very limited. METHODS: The results of quantitative X-ray diffraction phase
      analysis performed on 286 kidney stones extracted during endourological surgery
      or expelled spontaneously were retrospectively analyzed. Stone composition and
      crystallite size were determined and were compared to the burden occupying the
      pelvicalyceal system. RESULTS: A total of 286 renal stones were analyzed. Stones
      were low burden and high burden in 242 and 44 of cases, respectively. We observed
      statistically significant association of phosphates and urates with high-burden
      stones in contrast to oxalates, which formed mainly low-burden stones.
      Crystallite sizes were available for 179 stones. Large-sized crystallites of
      calcium oxalate monohydrate and hydroxyl apatite formed low-burden stones,
      whereas small-sized crystallites formed staghorn stones. Struvite and urates had
      a uniform average size of crystallites. CONCLUSION: Oxalate stones have
      statistically significant association with smaller stones, whereas high-burden
      calculi are significantly associated with urates and phosphates, especially the
      struvite type. The smaller the crystallite size is to start with, the larger will
      be the ultimate stone burden. This rule is followed by calcium oxalate
      monohydrate and Apatite minerals.

PMID- 22990053
TI  - Visualisation of the lymph node pathway in real time by laparoscopic radioisotope
      and fluorescence-guided sentinel lymph node dissection in prostate cancer
      staging.
AB  - OBJECTIVE: To investigate the feasibility of visualizing lymphatic drainage of
      the prostate using indocyanine green. The results were compared with standard
      radio-guided sentinel lymph node dissection and validated by extended pelvic
      lymph node dissection. METHODS: From March 2010 to October 2011, (99m)Tc-labelled
      colloid (18 hours before surgery) and indocyanine green (immediately before
      surgery) were injected transrectally into the prostate of 26 consecutive
      patients. A dedicated laparoscopic fluorescence imaging system and a commercially
      available laparoscopic gamma-probe were used. Lymphatic vessels were visualized
      in real time and followed to identify the sentinel lymph node. All detected hot
      spots (fluorescent signals and/or radioactivity) were considered as sentinel
      lymph nodes, dissected, and removed. Each specimen of excised tissue was labeled
      according to its anatomic position and whether it was positive for radioactivity
      or fluorescence. Every patient underwent laparoscopic extended pelvic lymph node
      dissection and radical prostatectomy. RESULTS: Five-hundred eighty-two lymph
      nodes (median 22, range 11-36) were removed. Two characteristic drainage patterns
      were identified: one was associated with the medial umbilical ligament and the
      other with the internal iliac region. A direct connection with para-aortic lymph
      nodes was found in 3 patients. A single solitary micrometastasis was visualized
      by fluorescence navigation alone. A strong correlation was established between
      radioactive and fluorescent lymph nodes. Compared with radio-guided sentinel
      lymph node dissection alone, additional fluorescence-guided sentinel lymph node
      dissection demonstrated a further 120 lymph nodes. CONCLUSION: Using the
      described technique of fluorescence navigation, not only lymph nodes but also
      lymphatic vessels are visualized in real time. The technique appears to be as
      effective as sentinel lymph node dissection but easier to apply.

PMID- 22990054
TI  - Inflammatory myofibroblastic tumor of the bladder in a 10-year-old girl.
AB  - Inflammatory myofibroblastic tumors (IMTs) of the bladder are rarely encountered
      bladder tumors during the pediatric age. The unknown malignant potential of these
      tumors causes controversy for their treatment and follow-up. We report a 10-year
      old girl who was referred to our clinic with dysuria and enuresis. The
      clinicopathological evaluation was compatible with IMT and a bladder preserving
      approach was used. There was no recurrence in the first year of follow-up
      examinations.

PMID- 22990057
TI  - Editorial comment.

PMID- 22990058
TI  - Cyst infection in unilateral renal cystic disease and the role of diffusion
      weighted magnetic resonance imaging.
AB  - In multicystic renal diseases, cyst infection is a complex issue because of the
      absence of validated diagnostic methods. Unilateral renal cystic disease is a
      rare multicystic disease, believed to have an acquired maldevelopmental origin.
      Unilateral renal cystic disease is often confused with autosomal dominant
      polycystic kidney disease but has some distinguishing characteristics: unilateral
      localization, negative family history, and no progression to chronic renal
      failure. We describe a case of unilateral renal cystic disease with cyst
      infection that could be detected by diffusion-weighted magnetic resonance
      imaging, but not by conventional imaging techniques. Diffusion-weighted magnetic
      resonance imaging can be useful for detecting infected cysts, especially in
      multicystic renal diseases.

PMID- 22990056
TI  - Monitoring quality of life among prostate cancer survivors: the feasibility of
      automated telephone assessment.
AB  - OBJECTIVE: To examine the feasibility of using automated interactive voice
      response calls to assess prostate cancer survivor quality of life (QOL). In light
      of an increasing focus on patient-centered outcomes, innovative and efficient
      approaches to monitor QOL among prostate cancer survivors are increasingly
      valuable. METHODS: Forty prostate cancer survivors less than 1 year post
      treatment were enrolled at a university-based cancer center clinic from July
      through August 2011. We adapted the Expanded Prostate Cancer Index Composite
      (EPIC) survey, a prostate cancer-specific QOL instrument, for use via personal
      telephone with interactive voice response. We compared written vs interactive
      voice response EPIC scores across urinary, sexual, bowel, and vitality domains.
      RESULTS: The median age of respondents was 63 years (range, 41-76 years) and the
      majority had undergone surgery (97.5%). The entire interactive voice response
      call was completed by 35 participants (87.5%). Over half of all interactive voice
      response calls were answered after 2 attempts with a median length of 11.3
      minutes. On average, interactive voice response EPIC scores were slightly lower
      than written scores (-2.1 bowel, P = .05; -4.6 urinary incontinence, P < .01).
      Test-retest reliability was very high for urinary incontinence (r = .97) and
      sexual function domains (r = .96). Although mean scores were similar for other
      domains, their distributions had significant ceiling effects limiting our
      reliability measure interpretation. CONCLUSION: Automated interactive voice
      response calls are a feasible strategy for assessing prostate cancer survivor
      QOL. Interactive voice response could provide a low cost, sustainable, and
      systematic approach to measuring patient-centered outcomes, conducting
      comparative effectiveness research, and monitoring the quality of prostate cancer
      care.

PMID- 22990059
TI  - Testicular capillary hemangioma presenting as an incidental contralateral lesion
      in a child with cryptorchidism.
AB  - Testicular capillary hemangioma is a rare benign vascular lesion. Appropriate
      recognition is paramount to ensuring testicular preservation. The authors present
      a case with an atypical presentation along with a review of the literature.
      Classic epidemiologic, clinical, and pathologic characteristics, as well as
      recommended surgical intervention are provided.

PMID- 22990060
TI  - Increased body mass index is associated with larger renal calculi.
AB  - OBJECTIVE: To examine the relationship between the body mass index and the size
      of renal stones in a group of patients with urolithiasis. METHODS: One-hundred
      seventy-three patients with renal stones were enrolled. Body mass index was
      calculated on the basis of height and weight measurements, and stone size was
      either measured accurately (143 patients) or estimated by the radiologist or
      managing urologist (30 patients). Body mass index and stone size were then cross
      tabulated and the results were analyzed. RESULTS: Patients with a body mass index
      of >= 25 kg/m(2) (overweight or obese) were found to have 29 (16.8%) small, 84
      (48.5%) medium, and 25 (14.5%) large stones, whereas patients in the underweight
      or normal body mass index categories had 7 (9.5%) small, 19 (10.9%) medium, and 9
      (10.6%) large stones. Of the study group, 109/173 (63%) were found to be
      overweight or obese, of whom all had renal stones >= 1 cm, ie, medium or large,
      when measured at the greatest diameter, indicating a tendency to have larger
      stones with increasing body mass index that was statistically significant (P =
      .0001). CONCLUSION: A clear relationship exists between increased body mass index
      and renal stone size, with overweight and obese patients having medium and large
      stones more frequently than patients with underweight or normal body mass index.

PMID- 22990061
TI  - Maximum isometric detrusor pressure to measure bladder strength in men with
      postprostatectomy incontinence.
AB  - OBJECTIVE: To describe the use of isovolumetric detrusor pressure (Piso) in men
      with postprostatectomy incontinence and compare the rates of detrusor
      underactivity using Piso versus other common measurements/surrogates of bladder
      strength. METHODS: We evaluated 62 men referred to our institution during a 3
      year period for workup of postprostatectomy incontinence. During videourodynamic
      evaluation, the maximum Piso was measured using a mechanical stop test--with the
      examiner gently occluding the penile urethra during volitional voiding.
      Statistical analysis was performed to evaluate the effect of patient variables on
      Piso. RESULTS: The mean Piso was 54.6 +/- 25.4 cm H(2)O. The Piso was <50 cm
      H(2)O in 40%. Isometric strength did not significantly correlate with age,
      interval since radical prostatectomy, abdominal leak point pressure, maximal
      urethral closure pressure, or pad use. The bladder contractility index and other
      approximations of detrusor underactivity were not predictive of low isometric
      pressure. CONCLUSION: Detrusor underactivity is relatively common in men with
      postprostatectomy incontinence, with 40% demonstrating a Piso <50 cm H(2)O. Our
      data do suggest, however, that the use of common bladder contractility nomograms,
      such as the bladder contractility index, might not be appropriate in this
      population.

PMID- 22990062
TI  - Bipolar transurethral resection of the prostate causes deeper coagulation depth
      and less bleeding than monopolar transurethral prostatectomy.
AB  - OBJECTIVE: To investigate the hemostatic capability of mono- and bipolar
      transurethral resection of the prostate by comparing the perioperative blood loss
      with the coagulation depth achieved with mono- and bipolar transurethral
      resection of the prostate. METHODS: A total of 136 patients with lower urinary
      tract symptoms associated with benign prostatic hyperplasia were randomized to
      undergo transurethral resection of the prostate using either a monopolar system
      (Karl Storz, Co., Tuttlingen, Germany) or a gyrus PlasmaKinetic bipolar system
      (Gyrus-ACMI Corporation, Maple Grove, MN). The operative time, resected tissue
      weight, decline in serum sodium and hemoglobin, postoperative bleeding, and the
      coagulation depth were compared. RESULTS: There were no statistically significant
      differences in operative time, resected tissue weight, and capsular perforation.
      The decline in hemoglobin and serum sodium was 1.15 +/- 0.53 g/dL and 4.57 +/-
      0.71 mmol/L in monopolar transurethral resection of the prostate group,
      respectively, whereas they fell only 0.71 +/- 0.42 g/dL and 2.02 +/- 0.53 mmol/L
      in the bipolar transurethral resection of the prostate group, respectively (P
      <.001). The rate of postoperative bleeding was significantly higher in the
      monopolar transurethral resection of the prostate group (P = .027). The
      coagulation depths with mono- and bipolar transurethral resection of the prostate
      were 127.56 +/- 27.76 and 148.48 +/- 31.64 MUm, respectively (P <.001).
      CONCLUSION: Our results demonstrate that bipolar transurethral resection of the
      prostate causes less intraoperative hemoglobin drop and postoperative bleeding
      than monopolar transurethral resection of the prostate, which may be associated
      with the deeper coagulation depth of bipolar transurethral resection of the
      prostate.

PMID- 22990063
TI  - Effects of prolyl 4-hydroxylase inhibitor on bladder function, bladder
      hypertrophy and collagen subtypes in a rat model with partial bladder outlet
      obstruction.
AB  - OBJECTIVE: To investigate the effects of prolyl 4-hydroxylase (P4H) inhibitor on
      the bladder in rats with partial bladder outlet obstruction. METHODS: Forty-five
      female Sprague-Dawley rats were divided into 3 groups; partial bladder outlet
      obstruction with P4H inhibitor 20 mg/kg (groups A1, A2, and A4, each n = 5),
      partial bladder outlet obstruction with normal saline (groups B1, B2, and B4,
      each n = 5), and normal control (groups C1, C2, and C4, each n = 5). After
      partial bladder outlet obstruction for 1, 2, and 4 weeks in the groups A and B,
      respectively, the inhibitor or normal saline were administered orally at the
      indicated dosage once a day for 2 weeks. After either 3, 4, or 6 weeks, the
      bladders were removed after cystometry. RESULTS: The pressure and volume
      parameters from the cystometry and the muscle thickness from the Masson trichrome
      staining of groups A and B increased significantly compared to those in group C
      (P < .05), and those in group A were significantly lower than those of group B (P
      < .05). Based on immunohistochemical staining and reverse transcription
      polymerase chain reaction, P4H expression in groups A and B was increased
      compared with that in group C. Furthermore, P4H expression showed a larger
      decrease in group A compared to that in group B. Collagens I and III protein
      expressions increased with partial bladder outlet obstruction in comparison with
      that of group C, and expression in group A was marginally decreased compared with
      expression in group B. CONCLUSION: Our data suggest that the P4H inhibitor may
      improve bladder function and reduce the bladder fibrosis caused by partial
      bladder outlet obstruction.

PMID- 22990064
TI  - Comparison of laparoendoscopic single-site and multiport laparoscopic radical and
      partial nephrectomy: a prospective, nonrandomized study.
AB  - OBJECTIVE: To prospectively compare outcomes of laparoendoscopic single-site and
      multiport laparoscopic radical nephrectomy and partial nephrectomy, focusing on
      postoperative pain and analgesic requirement. METHODS: Nonrandomized, prospective
      comparison of laparoendoscopic single-site and multiport laparoscopic radical
      nephrectomy and partial nephrectomy. Thirty-four patients underwent
      laparoendoscopic single-site (17 radical nephrectomy/17 partial nephrectomy); 42
      underwent multiport laparoscopy (28 radical nephrectomy/14 partial nephrectomy)
      from February 2009 to February 2010. Laparoendoscopic single-site transperitoneal
      access was obtained by periumbilical incision through which all trocars were
      inserted. Laparoendoscopic radical nephrectomy/partial nephrectomy recapitulated
      steps of multiport laparoscopic radical nephrectomy/partial nephrectomy.
      Demographics/tumor characteristics, outcomes, and complications were analyzed.
      RESULTS: Forty-two of 42 multiport laparoscopic and 32/34 laparoendoscopic single
      site cases were successfully performed. Mean follow-up was 16.2 months. For
      laparoendoscopic single-site and multiport laparoscopy groups mean operating room
      time (min) was 159.3 vs 158.9 (P = .952); mean estimated blood loss (mL) was
      175.7 vs 156.1 (P = .553); percent transfused was 2.9% vs 0% (P = .925). No
      significant differences in complications were noted (P = .745). Significant
      decrease in analgesic use (6 morphine equivalents vs 11.6, P < .001) and
      discharge pain score (1.7 vs 2.7, P < .01) were noted in laparoendoscopic single
      site vs multiport laparoscopic radical nephrectomy. For laparoendoscopic single
      site partial nephrectomy and multiport laparoscopic partial nephrectomy, no
      significant differences were noted for tumor diameter (1.8 vs 2.0 cm, P = .57),
      RENAL score (0.962), ischemia time (28.6 vs 27.5 minutes, P = .70), and
      preoperative (P = .78)/postoperative creatinine (P = .32). For laparoendoscopic
      single-site radical nephrectomy and multiport laparoscopic radical nephrectomy,
      no significant differences were noted for mean tumor diameter (5.6 vs 5.3 cm, P =
      .63), RENAL score (P = .815), and mean operative time (142.3 vs 155.4 minutes P =
      .13). CONCLUSION: In this well-matched, prospective comparison, laparoendoscopic
      single-site is comparable with multiport laparoscopic surgery in terms of
      perioperative parameters and may confer benefit with respect to analgesic
      requirement. Randomized evaluation and longer-term follow-up are necessary.

PMID- 22990065
TI  - Editorial comment.

PMID- 22990066
TI  - The possible factors influencing the effect of cardiology intervention on
      troponin elevated patients after orthopaedic surgery.

PMID- 22990067
TI  - Effects of CYP2C19 variant alleles on postclopidogrel platelet reactivity and
      clinical outcomes in an actual clinical setting in China.
AB  - Whether the current pharmacogenetic knowledge of clopidogrel could be translated
      into Chinese clinical practice is yet to be defined. To address this issue, we
      assessed the relation of single nucleotide polymorphisms within genes modulating
      clopidogrel absorption (ABCB1), metabolic activation (CYP2B6, CYP2D6, CYP3A4,
      CYP2C9, and CYP2C19), and biologic activity (P2RY12) to the response of
      clopidogrel as measured by ex-vivo platelet reactivity and ischemic events during
      half a year of follow-up. Only CYP2C19*2 and *3, of the investigated
      polymorphisms, were associated with postclopidogrel platelet aggregation and the
      presence of high platelet reactivity. Moreover, the effect of the CYP2C19*2
      versus the *3 allele on platelet reactivity did not differ. Although the carriage
      of one or two CYP2C19 loss-of-function alleles, irrespective of the CYP2C19*2 or
      *3 allele, increased the propensity for high platelet reactivity, only the two
      loss-of-function allele carriage was associated with clinical outcome in the
      first 6 months.

PMID- 22990068
TI  - Transmetallation between metal-only Lewis pairs: a new rhodium alane complex.
AB  - In this communication, synthesis of a rhodium alane Lewis adduct,
      [Cp(Me(3)P)(2)Rh->AlCl(3)], is reported. Given that direct synthesis using
      aluminium trichloride failed, a convenient transmetallation reaction was applied.
      The new MOLP was analysed by single crystal X-ray diffraction, multinuclear NMR
      spectroscopy and density functional theory calculations.

PMID- 22990069
TI  - The Food and Drug Administration's role in establishing and maintaining
      safeguards for contact lenses and contact lens care products.

PMID- 22990070
TI  - Preclinical research to aid in the development of test methods for contact lenses
      and their care products.

PMID- 22990071
TI  - Exhaled breath condensate pH is influenced by respiratory droplet dilution.
AB  - Several studies support that airway acid stress plays a role in the
      pathophysiology of asthma. Exhaled breath condensate pH (EBC pH) was suggested as
      a surrogate marker of airway acidification. The dilution of airway lining fluid
      (ALF) acids and bases by alveolar water may influence condensate pH, but it has
      not been studied yet. The aim of our study was to investigate the relationship
      between EBC pH and ALF dilution in EBC samples obtained from asthmatic and
      healthy subjects. EBC was collected from 55 asthmatic and 57 healthy subjects for
      pH and conductivity measurements. Fractional exhaled nitric oxide (FE(NO)) and
      lung function tests were also performed in asthmatic patients. EBC pH was
      determined after 10 min of argon deareation and the dilution was estimated by the
      measurement of conductivity in vacuum-treated samples. There was no difference
      either in EBC pH or dilution between the two groups. However, a significant
      relationship was found between EBC pH and dilution in both groups (p < 0.05, r = 
      0.35 and r = -0.29, asthmatic and healthy groups, respectively). Our results
      suggest important methodological aspect indicating that EBC pH is affected by
      respiratory droplet dilution, and this effect should be taken into consideration
      when interpreting EBC pH data.

PMID- 22990072
TI  - Cell polarisation and the immunological synapse.
AB  - Directed secretion by immune cells requires formation of the immunological
      synapse at the site of cell-cell contact, concomitant with a dramatic induction
      of cell polarity. Recent findings provide us with insights into the various steps
      that are required for these processes: for example, the first identification of a
      protein at the centrosome that regulates its relocation to the plasma membrane;
      the use of super-resolution imaging techniques to reveal a residual actin network
      at the immunological synapse that may permit secretory granule exocytosis; and
      the drawing of parallels between primary cilia and IS architecture. Here we
      discuss these and other novel findings that have advanced our understanding of
      the complex process of immunological synapse formation and subsequent induced
      cell polarity in immune cells.

PMID- 22990074
TI  - Graphene/zinc nano-composites by electrochemical co-deposition.
AB  - We describe for the first time the electrochemical co-deposition of composites
      based on a reactive base metal and graphene directly from a one-pot aqueous
      mixture containing graphene oxide and Zn(2+). In order to overcome stability
      issues the Zn(2+) concentration was kept below a critical threshold
      concentration, ensuring stable graphene oxide suspensions in the presence of
      cationic base metal precursors. This approach ensures the compatibility between
      the cationic base metal precursor and graphene oxide, which is more challenging
      compared to previously reported anionic noble metal complexes. Spectroscopic
      evidence suggests that the reason for destabilisation is zinc complexation
      involving the carboxylate groups of graphene oxide. The composition of the
      electrodeposited co-composites can be tuned by adjusting the concentration of the
      precursors in the starting mixture. The nano-composites show zinc particles (<3
      nm) being uniformly dispersed amongst the graphene sheets. It is also
      demonstrated that the composites are electrochemically active and suitable for
      energy storage and energy conversion applications. However, a factor limiting the
      discharge efficiency is the reactivity of the base metal (low reduction potential
      and small particle size) which undergoes rapid oxidation when exposed to aqueous
      electrolytes.

PMID- 22990073
TI  - Transcriptional regulation of the mouse CD11c promoter by AP-1 complex with JunD
      and Fra2 in dendritic cells.
AB  - CD11c, a member of the beta(2) integrin family of adhesion molecule, is expressed
      on the surface of myeloid lineages and activated lymphoid cells and forms a
      heterodimeric receptor with CD18. We analyzed the mouse CD11c promoter structure
      to elucidate the transcriptional regulation in dendritic cells (DCs). By reporter
      assay, the -84/-65 region was identified to be essential for activity of the
      mouse CD11c promoter in the mouse bone marrow-derived (BM) DCs and monocyte cell
      line RAW264.7. An electrophoretic mobility shift assay using a number of
      antibodies against transcription factors revealed that the target region was
      recognized by a complex including JunD and Fra2, which are transcription factors
      belonging to the AP-1 family. The direct interaction of JunD and Fra2 with the
      CD11c promoter was further confirmed by a chromatin immunoprecipitation assay
      using CD11c-positive cells purified from BMDCs. Finally, mouse JunD and/or Fra2
      siRNA was introduced into BMDCs to evaluate the involvement of these factors
      against CD11c transcription and found that Fra2 siRNA reduced cell surface
      expression level of CD11c. These results indicate that AP-1 composed with JunD
      and Fra2 protein plays a primary role in enhancing the transcription level of the
      CD11c gene in DC.

PMID- 22990075
TI  - Retreatment tuberculosis in a South African community: the role of re-infection,
      HIV and antiretroviral treatment.
AB  - BACKGROUND: Limited data exist on the impact of human immunodeficiency virus
      (HIV) or antiretroviral treatment (ART) on retreatment tuberculosis (TB).
      METHODS: Retreatment TB episodes between 2001 and 2010 in a high HIV and TB
      burden community were linked to first-episode treatment  outcomes, HIV status and
      ART use. Genotypic analysis of Mycobacterium tuberculosis isolates distinguished
      re-infection from reactivation TB. RESULTS: A total of 2027 TB episodes occurred
      in 1755 adults: 564 were retreatment cases. New patients who interrupted or
      failed initial treatment,  were HIV-positive or were not on ART more frequently
      developed retreatment TB (respectively P < 0.001, P = 0.01 and P = 0.02). Time
      intervals between successive diagnoses were shorter in patients who
      interrupted/failed treatment compared to those with favourable initial  treatment
      outcomes (P < 0.001), but did not vary by HIV status or ART use. Genotypic data
      were available for 40 successive diagnoses, of which 19 had matching M.
      tuberculosis strains. Matching strains were associated with HIV-negative status
      (P < 0.001), treatment  interruption/failure (P = 0.04) and shorter intervals
      between diagnoses (P = 0.02). HIV-positive patients and patients on ART were more
      likely to have non-matched strains (P = 0.01 and P = 0.03). CONCLUSION: Among HIV
      negative patients, retreatment TB was predominantly  due to reactivation
      following poor initial treatment outcomes. In HIV-positive patients re-infection
      TB was more common, particularly among those on ART.

PMID- 22990076
TI  - Regulators of blood lipids and lipoproteins? PPARdelta and AMPK, induced by
      exercise, are correlated with lipids and lipoproteins in overweight/obese men and
      women.
AB  - PPARdelta is a transcription factor regulating the expression of genes involved
      in oxidative metabolism, which may regulate blood cholesterols through
      transcription of oxidative and lipoprotein metabolism genes. To determine the
      association of skeletal muscle PPARdelta content with blood lipids and
      lipoproteins before and following exercise, overweight and obese men (n = 9) and
      women (n = 7) were recruited; age, BMI, body fat percentage, and Vo(2max) were
      (means +/- SE) 45 +/- 2.5 yr, 31.9 +/- 1.4 kg/m(-2), 41.1 +/- 1.5%, and 26.0 +/-
      1.3 mLO(2).kg(-1).min(-1), respectively. Subjects performed 12 wk of endurance
      exercise training (3 sessions/wk, progressing to 500 kcal/session). To assess the
      acute exercise response, subjects performed a single exercise session on a
      treadmill (70% Vo(2max), 400 kcal energy expenditure) before and after training.
      Muscle and blood samples were obtained prior to any exercise and 24 h after each
      acute exercise session. Muscle was analyzed for protein content of PPARdelta,
      PPARalpha, PGC-1alpha, AMPKalpha, and the oxidative and lipoprotein markers
      FAT/CD36, CPT I, COX-IV, LPL, F(1) ATPase, ABCAI, and LDL receptor. Blood was
      assessed for lipids and lipoproteins. Repeated-measures ANOVA revealed no
      influence of sex on measured outcomes. PPARdelta, PGC-1alpha, FAT/CD36, and LPL
      content were enhanced following acute exercise, whereas PPARalpha, AMPKalpha, CPT
      I, and COX-IV content were enhanced only after exercise training. PPARdelta
      content negatively correlated with total and LDL cholesterol concentrations
      primarily in the untrained condition (r <= -0.4946, P < 0.05), whereas AMPKalpha
      was positively correlated with HDL cholesterol concentrations regardless of
      exercise (r >= 0.5543, P < 0.05). Our findings demonstrate exercise-induced
      expression of skeletal muscle PPARs and their target proteins, and this
      expression is associated with improved blood lipids and lipoproteins in obese
      adults.

PMID- 22990077
TI  - Clostridium difficile colitis: review of the therapeutic approach.
AB  - Clostridium difficile infection (CDI) is the leading cause of antibiotic
      associated and nosocomial infectious diarrhea. Presenting as clostridium
      difficile colitis, it is a significant cause of morbidity and mortality.
      Metronidazole is regarded as the agent of choice for CDl therapy and also for the
      first recurrence in most patients with mild to moderate CDI. Vancomycin is
      recommended as an initial therapy for patients with severe CDI. With recent Food
      and Drug Administration-approval fidaxomicin is available for clinical use and is
      as effective as vancomycin with lower relapse rates. Rifaximin and fecal
      bacteriotherapy are alternative approaches in patients with severe or refractory
      CDI, before surgical intervention. Antibiotic research is ongoing to add
      potential new drugs such as teicoplanin, ramoplanin, fusidic acid, nitazoxanide,
      rifampin, bacitracin to our armamentarium. Role of toxin-binding agents is still
      questionable. Monoclonal antibody and intravenous immunoglobulin are still
      investigational therapies that could be promising options. The ongoing challenges
      in the treatment of CDI include management of recurrence and presence of
      resistance strains such as NAP1/BI/027, but early recognition of surgical
      candidates can potentially decrease mortality in CDI.

PMID- 22990078
TI  - Note from the editors.

PMID- 22990080
TI  - Transparently, with validation.

PMID- 22990079
TI  - Building better models: if we build them, will policy makers use them? Toward
      integrating modeling into health care decisions.

PMID- 22990081
TI  - Transparency and reproducible research in modeling: why we need it and how to get
      there.

PMID- 22990082
TI  - Modeling good research practices--overview: a report of the ISPOR-SMDM Modeling
      Good Research Practices Task Force-1.
AB  - Models-mathematical frameworks that facilitate estimation of the consequences of
      health care decisions-have become essential tools for health technology
      assessment. Evolution of the methods since the first ISPOR modeling task force
      reported in 2003 has led to a new task force, jointly convened with the Society
      for Medical Decision Making, and this series of seven papers presents the updated
      recommendations for best practices in conceptualizing models; implementing state
      transition approaches, discrete event simulations, or dynamic transmission
      models; dealing with uncertainty; and validating and reporting models
      transparently. This overview introduces the work of the task force, provides all
      the recommendations, and discusses some quandaries that require further
      elucidation. The audience for these papers includes those who build models,
      stakeholders who utilize their results, and, indeed, anyone concerned with the
      use of models to support decision making.

PMID- 22990083
TI  - Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research
      Practices Task Force-2.
AB  - The appropriate development of a model begins with understanding the problem that
      is being represented. The aim of this article is to provide a series of consensus
      based best practices regarding the process of model conceptualization. For the
      purpose of this series of papers, the authors consider the development of models
      whose purpose is to inform medical decisions and health-related resource
      allocation questions. They specifically divide the conceptualization process into
      two distinct components: the conceptualization of the problem, which converts
      knowledge of the health care process or decision into a representation of the
      problem, followed by the conceptualization of the model itself, which matches the
      attributes and characteristics of a particular modeling type to the needs of the
      problem being represented. Recommendations are made regarding the structure of
      the modeling team, agreement on the statement of the problem, the structure,
      perspective and target population of the model, and the interventions and
      outcomes represented. Best practices relating to the specific characteristics of
      model structure, and which characteristics of the problem might be most easily
      represented in a specific modeling method, are presented. Each section contains a
      number of recommendations that were iterated among the authors, as well as the
      wider modeling taskforce, jointly set up by the International Society for
      Pharmacoeconomics and Outcomes Research and the Society for Medical Decision
      Making.

PMID- 22990084
TI  - State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research
      Practices Task Force-3.
AB  - State-transition modeling (STM) is an intuitive, flexible, and transparent
      approach of computer-based decision-analytic modeling, including both Markov
      model cohort simulation as well as individual-based (first-order Monte Carlo)
      microsimulation. Conceptualizing a decision problem in terms of a set of (health)
      states and transitions among these states, STM is one of the most widespread
      modeling techniques in clinical decision analysis, health technology assessment,
      and health-economic evaluation. STMs have been used in many different populations
      and diseases, and their applications range from personalized health care
      strategies to public health programs. Most frequently, state-transition models
      are used in the evaluation of risk factor interventions, screening, diagnostic
      procedures, treatment strategies, and disease management programs.

PMID- 22990085
TI  - Modeling using discrete event simulation: a report of the ISPOR-SMDM Modeling
      Good Research Practices Task Force-4.
AB  - Discrete event simulation (DES) is a form of computer-based modeling that
      provides an intuitive and flexible approach to representing complex systems. It
      has been used in a wide range of health care applications. Most early
      applications involved analyses of systems with constrained resources, where the
      general aim was to improve the organization of delivered services. More recently,
      DES has increasingly been applied to evaluate specific technologies in the
      context of health technology assessment. The aim of this article is to provide
      consensus-based guidelines on the application of DES in a health care setting,
      covering the range of issues to which DES can be applied. The article works
      through the different stages of the modeling process: structural development,
      parameter estimation, model implementation, model analysis, and representation
      and reporting. For each stage, a brief description is provided, followed by
      consideration of issues that are of particular relevance to the application of
      DES in a health care setting. Each section contains a number of best practice
      recommendations that were iterated among the authors, as well as the wider
      modeling task force.

PMID- 22990086
TI  - Dynamic transmission modeling: a report of the ISPOR-SMDM Modeling Good Research
      Practices Task Force Working Group-5.
AB  - The transmissible nature of communicable diseases is what sets them apart from
      other diseases modeled by health economists. The probability of a susceptible
      individual becoming infected at any one point in time (the force of infection) is
      related to the number of infectious individuals in the population, will change
      over time, and will feed back into the future force of infection. These nonlinear
      interactions produce transmission dynamics that require specific consideration
      when modeling an intervention that has an impact on the transmission of a
      pathogen. Best practices for designing and building these models are set out in
      this paper.

PMID- 22990087
TI  - Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM
      Modeling Good Research Practices Task Force Working Group-6.
AB  - A model's purpose is to inform medical decisions and health care resource
      allocation. Modelers employ quantitative methods to structure the clinical,
      epidemiological, and economic evidence base and gain qualitative insight to
      assist decision makers in making better decisions. From a policy perspective, the
      value of a model-based analysis lies not simply in its ability to generate a
      precise point estimate for a specific outcome but also in the systematic
      examination and responsible reporting of uncertainty surrounding this outcome and
      the ultimate decision being addressed. Different concepts relating to uncertainty
      in decision modeling are explored. Stochastic (first-order) uncertainty is
      distinguished from both parameter (second-order) uncertainty and from
      heterogeneity, with structural uncertainty relating to the model itself forming
      another level of uncertainty to consider. The article argues that the estimation
      of point estimates and uncertainty in parameters is part of a single process and
      explores the link between parameter uncertainty through to decision uncertainty
      and the relationship to value-of-information analysis. The article also makes
      extensive recommendations around the reporting of uncertainty, both in terms of
      deterministic sensitivity analysis techniques and probabilistic methods. Expected
      value of perfect information is argued to be the most appropriate presentational
      technique, alongside cost-effectiveness acceptability curves, for representing
      decision uncertainty from probabilistic analysis.

PMID- 22990088
TI  - Model transparency and validation: a report of the ISPOR-SMDM Modeling Good
      Research Practices Task Force-7.
AB  - Trust and confidence are critical to the success of health care models. There are
      two main methods for achieving this: transparency (people can see how the model
      is built) and validation (how well it reproduces reality). This report describes
      recommendations for achieving transparency and validation, developed by a task
      force appointed by the International Society for Pharmacoeconomics and Outcomes
      Research (ISPOR) and the Society for Medical Decision Making (SMDM).
      Recommendations were developed iteratively by the authors. A nontechnical
      description should be made available to anyone-including model type and intended
      applications; funding sources; structure; inputs, outputs, other components that
      determine function, and their relationships; data sources; validation methods and
      results; and limitations. Technical documentation, written in sufficient detail
      to enable a reader with necessary expertise to evaluate the model and potentially
      reproduce it, should be made available openly or under agreements that protect
      intellectual property, at the discretion of the modelers. Validation involves
      face validity (wherein experts evaluate model structure, data sources,
      assumptions, and results), verification or internal validity (check accuracy of
      coding), cross validity (comparison of results with other models analyzing same
      problem), external validity (comparing model results to real-world results), and
      predictive validity (comparing model results with prospectively observed events).
      The last two are the strongest form of validation. Each section of this paper
      contains a number of recommendations that were iterated among the authors, as
      well as the wider modeling task force jointly set up by the International Society
      for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision
      Making.

PMID- 22990089
TI  - Carbon nanotube growth from Langmuir-Blodgett deposited Fe3O4 nanocrystals.
AB  - We investigate colloidal Fe(3)O(4) nanocrystals as a catalyst system for carbon
      nanotube (CNT) growth that allows for decoupling the CNT growth step from the
      catalyst shaping and activation step. The system consists of 6.4 nm Fe(3)O(4)
      nanocrystals synthesized using a solution-based thermal decomposition reaction
      and, subsequently, transferred as hexagonally ordered Langmuir-Blodgett (LB)
      monolayers on TiN substrates. We demonstrate for the first time aligned CNT
      growth from LB deposited nanocrystals on a metallic underlayer. The hexagonally
      ordered monolayers of catalyst particles show promising stability up to the CNT
      growth temperature. In situ TEM heating experiments were performed to find this
      onset of particle deformation and showed stability of the nanoparticles up to 600
      degrees C. The particle coalescence at high temperatures was also evidenced by
      the increasing CNT diameter, from 9.5 nm at 580  degrees C to 16 nm at 630 
      degrees C. By choosing to work at temperatures below the onset particle
      coalescence temperature, equivalent CNT diameters were obtained under different
      catalyst activation and growth conditions. The high stability of the catalyst on
      the metallic underlayer enables us to study CNT growth kinetics independently of
      the catalyst shaping step. This work opens a route towards combining growth
      studies with an electrical evaluation of the CNT growth as the TiN can be used as
      the bottom contact.

PMID- 22990091
TI  - Hyperandrogenism and intersex controversies in women's olympics.
AB  - International sports governing bodies such as the International Association for
      Athletics Federation and the International Olympic Committee have recently
      revised their policies for inclusion of athletes competing in women's
      international sports competitions. Previously, the focus was on verification of
      gender or femininity. The mishandling of Caster Semanya's case brought the
      complex issues of fairness with regard to athletes with disorders of sexual
      development or hyperandrogenism into both public and private debates. The new
      International Association for Athletics Federation and International Olympic
      Committee policies for inclusion in women's sporting events rest largely on the
      serum testosterone level, mandating that it be less than the lower limit of
      normal for men as the defining criteria. This report provides an overview of past
      problems and an update of the newly adopted policies for eligibility for
      competition in women's events. Endocrinologists will play a key role in the
      evaluation and treatment of women athletes who have elevated androgen levels,
      regardless of the underlying cause.

PMID- 22990090
TI  - The effect of maternal vitamin D concentration on fetal bone.
AB  - CONTEXT: Vitamin D deficiency during pregnancy may be associated with suboptimal
      fetal growth, but direct evidence is lacking. OBJECTIVES: The aim of the study
      was to validate a method for fetal femur volume (FV) measurement using three
      dimensional ultrasound and to detect correlations between FV and maternal vitamin
      D concentration. DESIGN, SETTING, AND PARTICIPANTS: A novel method for assessing
      FV consists of three ultrasound measurements-femur length, proximal metaphyseal
      diameter (PMD), and midshaft diameter-and a volume equation; this was validated
      by comparing ultrasound to computed tomography measurements in six pregnancies
      after mid-trimester termination. This method was then applied in a cohort of
      healthy pregnant women participating in the Southampton Women Survey. Fetal three
      dimensional ultrasound and maternal 25-hydroxyvitamin D [25(OH)D] levels were
      performed at 34 wk; dual-energy x-ray absorptiometry of the newborn was performed
      shortly after birth. Univariate and multiple linear regression analyses were
      performed between maternal characteristics and fetal outcomes. MAIN OUTCOME
      MEASURES: We performed ultrasound measurements of the fetal femur. RESULTS: In
      357 pregnant participants, serum 25(OH)D correlated significantly with FV (P =
      0.006; r = 0.147) and PMD (P = 0.001; r = 0.176); FV also demonstrated positive
      univariate correlations with maternal height (P < 0.001; r = 0.246), weight (P =
      0.003; r = 0.160), triceps skinfold thickness (P = 0.013; r = 0.134), and a
      borderline negative effect from smoking (P = 0.061). On multiple regression,
      independent predictors of FV were the maternal height and triceps skinfold
      thickness; the effect of 25(OH)D on FV was attenuated, but it remained
      significant for PMD. CONCLUSION: Using a novel method for assessing FV,
      independent predictors of femoral size were maternal height, adiposity, and serum
      vitamin D. Future trials should establish whether pregnancy supplementation with
      vitamin D is beneficial for the fetal skeleton, using FV and PMD as fetal outcome
      measures.

PMID- 22990092
TI  - Sex steroids, GHRH, somatostatin, IGF-I, and IGFBP-1 modulate ghrelin's dose
      dependent drive of pulsatile GH secretion in healthy older men.
AB  - CONTEXT: Ghrelin is a potent endogenous stimulator of GH secretion. However,
      clinical factors that regulate ghrelin dose-responsiveness are incompletely
      defined. OBJECTIVE: The aim of the study was to test the multipathway hypothesis
      that testosterone (T) and estradiol, GHRH, and somatostatin (SS) jointly modulate
      ghrelin's action. DESIGN/PARTICIPANTS/SETTING: Healthy older men (n = 21)
      participated in a double-blind, prospectively randomized, placebo (Pl)-controlled
      study in a Clinical Translational Research Center. INTERVENTIONS: To create a
      range of sex-steroid milieus, men received leuprolide + Pl (n = 10) or leuprolide
      + T addback (n = 11). Sixteen to 21 d later, subjects received three separate
      randomly ordered overnight constant i.v. infusions of saline, GHRH, and SS.
      Interactions between the peptide clamp and ghrelin were tested by superimposed
      injections of four randomly ordered bolus i.v. doses of ghrelin (0.03, 0.135,
      0.60, and 2.7 MUg/kg). GH was measured every 10 min, and GH responses were
      assessed by nonlinear dose-response analysis. Linear associations were assessed
      by stepwise regression. OUTCOME MEASURES/RESULTS: The descending numerical order
      of ghrelin efficacy (maximal GH secretory-burst mass; micrograms/liter) was 107
      (GHRH + Pl), 104 (GHRH + T), 73 (saline + T), 73 (SS + T), 60 (saline + Pl), and
      52 (SS + Pl) [means], wherein SS + T exceeded SS + Pl. GHRH and IGF binding
      protein-1 augmented, whereas IGF-I attenuated ghrelin potency. Age and IGF-I
      decreased ghrelin/GHRH synergy. Ghrelin sensitivity was independent of
      interventions. CONCLUSIONS: These studies introduce composite regulatory effects
      of sex hormones, GHRH, SS, IGF binding protein-1, and IGF-I on ghrelin dose
      responsiveness, suggesting multipathway modulation of GH-secretagogue action.

PMID- 22990093
TI  - Clinical characteristics of a cohort of 244 patients with congenital adrenal
      hyperplasia.
AB  - CONTEXT: Patients with congenital adrenal hyperplasia (CAH) often suffer from
      long-term complications secondary to chronic glucocorticoid therapy and
      suboptimal treatment regimens. OBJECTIVE: The aim of the study was to describe
      clinical characteristics of a large cohort of pediatric and adult CAH patients.
      DESIGN AND SETTING: We conducted a cross-sectional study of 244 CAH patients [183
      classic, 61 nonclassic (NC)] included in a Natural History Study at the National
      Institutes of Health. MAIN OUTCOME MEASURE(S): Outcome variables of interest were
      height sd score, obesity, hypertensive blood pressure (BP), insulin resistance,
      metabolic syndrome, bone mineral density, hirsutism (females), and testicular
      adrenal rest (TART). RESULTS: The majority had elevated or suppressed androgens,
      with varied treatment regimens. Mean adult height SD score was -1.0 +/- 1.1 for
      classic vs. -0.4 +/- 0.9 for NC patients (P = 0.015). Obesity was present in
      approximately one third of patients, across phenotypes. Elevated BP was more
      common in classic than NC patients (P <= 0.01); pediatric hypertensive BP was
      associated with suppressed plasma renin activity (P = 0.001). Insulin resistance
      was common in classic children (27%) and adults (38% classic, 20% NC); 18% of
      adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of
      adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC
      women). TART was found in classic males (33% boys; 44% men). CONCLUSIONS: Poor
      hormonal control and adverse outcomes are common in CAH, necessitating new
      treatments. Routine monitoring of classic children should include measuring BP
      and plasma renin activity. Osteoporosis prophylaxis and TART screening should
      begin during childhood. A longitudinal study is under way.

PMID- 22990094
TI  - Bone resorption is increased in pheochromocytoma patients and normalizes
      following adrenalectomy.
AB  - CONTEXT: The sympathetic nervous system (SNS) controls bone turnover in rodents,
      but it is uncertain whether a similar role for the SNS exists in humans.
      Pheochromocytomas are catecholamine-producing neuroendocrine tumors. Because
      catecholamines are the neurotransmitters of the SNS, we hypothesized that
      pheochromocytoma patients have increased bone turnover. OBJECTIVE: Our objective
      was to compare bone turnover in pheochromocytoma patients and controls. DESIGN
      AND SETTING: This retrospective case-control study was performed at the Endocrine
      Department of the Academic Medical Center of the University of Amsterdam in The
      Netherlands from 2007 until 2011. PATIENTS: All patients were screened for
      pheochromocytoma. Cases (n = 21) were identified by 24-h urinary excretion of
      fractionated metanephrines above the institutional reference value and confirmed
      by histology after adrenalectomy. All patients screened and diagnosed as not
      having pheochromocytoma served as controls (n = 126). MAIN OUTCOME MEASURE: The
      difference in bone turnover markers C-terminal cross-linking telopeptides of
      collagen type I (CTx) and procollagen type 1 N propeptide (P1NP) between cases
      and controls was the main outcome measure. RESULTS: CTx concentrations were
      higher in cases [343 ng/liter; interquartile range (IQR), 295 ng/liter] than in
      controls (232 ng/liter; IQR, 168 ng/liter; P < 0.001) and decreased after
      adrenalectomy [before, 365 ng/liter (IQR, 450 ng/liter); after, 290 ng/liter
      (IQR, 241 ng/liter); P = 0.044]. The effect remained after adjustment for
      possible confounders. P1NP concentrations did not differ. CONCLUSIONS: This study
      shows that pheochromocytoma patients have increased bone resorption, which
      normalizes after adrenalectomy. This finding supports the concept of regulation
      of bone remodeling by the SNS in humans.

PMID- 22990095
TI  - Innate small babies are metabolically healthy children.
AB  - BACKGROUND: Being born small for gestational age (SGA) is regarded as a risk
      factor for later metabolic complications. The SGA is defined as a birth weight
      below -2 SD of the distribution for sex and gestational age. However, the
      definition of SGA does not distinguish between those born after fetal growth
      restriction and innate SGA (iSGA). OBJECTIVE: Our objective was to test whether
      innate SGA infants show any metabolic complications at the age of 2 yr in
      comparison with infants born appropriate for gestational age (AGA). METHODS:
      Fifty-eight infants with family SGA risk factors (SGA in a previous pregnancy or
      among parents, maternal height less than -2 sd for adult height in French women,
      and small fetal size at second-trimester ultrasound examination) were
      prospectively followed from midgestation to 2 yr of age. Fetal growth velocity
      was measured from ultrasound measurements. Body composition and hormonal profile
      were measured at birth and 1 and 2 yr. RESULTS: Fetal growth velocity was not
      significantly different between iSGA and AGA (-0.17 +/- 0.2 vs. -0.17 +/- 0.3
      percentiles/d of gestation; P = 0.96). iSGA infants were significantly lighter at
      birth (-1.7 +/- 0.45 vs. 0.46 +/- 0.77 SD; P < 0.0001) and at 4 months of age (
      0.85 +/- 0.88 vs. 0.29 +/- 1 SD; P < 0.0001), and they remain so over follow-up (
      0.73 +/- 1.08 vs. 0.2 +/- 1.02 SD; P = 0.0014 at 2 yr). Height z-scores and
      percent fat time courses followed a similar pattern. No differences in any of the
      metabolic and hormonal parameters were observed between iSGA and AGA up to 2 yr
      (insulin at birth, 5.1 +/- 6.8 vs. 5.2 +/- 4.6 mIU/liter, P = 0.2; at 2 yr, 2 +/-
      1.6 vs. 2 +/- 1.5 mIU/liter, P = 0.66). CONCLUSION: Infants born iSGA do not
      experience severe fetal growth restriction and do not show any evidence of
      metabolic risk either at birth or in the first 2 yr of life.

PMID- 22990097
TI  - The coordinated expression, interaction and evolution of the neuroendocrine
      genes.
AB  - The neuroendocrine system is a complex biological system controlled by various
      neuropeptides and hormones. The evolution and network properties of
      neuroendocrine genes are analyzed along with their expression profiles. The
      neuroendocrine genes show very similar expression profiles and local network
      properties across a wide range of tissues consistent with the physiological roles
      of their proteins. Moreover, the coordinated evolution of 10 neuroendocrine genes
      involved in mammalian reproduction and homeostasis is demonstrated using several
      methods, such as correlated evolution, relative-rate test, relative-ratio test
      and codon usage bias. The neuroendocrine genes seem to evolve predominantly under
      similar selective strengths and regimes of purifying selection, which is well
      reflected in their evolutionary fingerprints. This result demonstrates for the
      first time a key role of natural selection in creating and maintaining a well
      designed neuroendocrine system at the genomic level. It also indicates that
      component properties of a complex system at a higher physiological scale may
      determine component properties at a lower genomic scale and/or vice versa.

PMID- 22990096
TI  - Circulating vitamin D metabolites and kidney disease in type 1 diabetes.
AB  - CONTEXT: Impaired vitamin D metabolism may contribute to the development and
      progression of diabetic kidney disease. OBJECTIVE: The aim of the study was to
      test associations of circulating vitamin D metabolites with risks of incident
      microalbuminuria, impaired glomerular filtration rate (GFR), and hypertension in
      type 1 diabetes. DESIGN: We performed a cohort study of 1193 participants in the
      Diabetes Control and Complications Trial (DCCT), a randomized clinical trial of
      intensive diabetes therapy, and its observational follow-up, the Epidemiology of
      Diabetes Interventions and Complications (EDIC) Study. We measured plasma
      concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and
      24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT and tested
      associations with incident microalbuminuria, impaired GFR, and hypertension over
      up to 16 yr of EDIC follow-up. RESULTS: At the time metabolites were measured,
      mean age was 32.4 yr; mean duration of diabetes, 7.5 yr; mean iothalamate GFR,
      132.9 ml/min/1.73 m(2); and geometric mean albumin excretion rate, 11.8 mg/24 h.
      Over follow-up, 166 cases of microalbuminuria, 54 cases of impaired GFR, and 541
      cases of hypertension were observed. Compared with 25(OH)D of at least 30 ng/ml,
      25(OH)D below 20 ng/ml was associated with a 65% higher risk of microalbuminuria
      (95% confidence interval, 7 to 154%) in adjusted analyses. Low concentrations of
      24,25-dihydroxyvitamin D, but not 1,25-dihydroxyvitamin D, were also associated
      with increased risk of microalbuminuria. No circulating vitamin D metabolite was
      associated with risk of impaired GFR or hypertension. CONCLUSIONS: Low plasma
      concentrations of 25(OH)D and 24,25-dihydroxyvitamin D are associated with
      increased risk of microalbuminuria in type 1 diabetes. In contrast, we did not
      find evidence linking impaired vitamin D metabolism to early GFR loss or the
      development of hypertension.

PMID- 22990098
TI  - Lessons from Penn State-a duty to act.

PMID- 22990099
TI  - Metastasizing pleomorphic adenoma presents intraorally: a case report and review
      of the literature.

PMID- 22990100
TI  - Intraoperative blood loss during orthognathic surgery is predicted by
      thromboelastography.
AB  - PURPOSE: The aim of this prospective study was to evaluate the predictive value
      of the viscoelastic properties of whole blood samples collected preoperatively in
      relation to intraoperative blood loss in patients subjected to orthognathic
      surgery. MATERIALS AND METHODS: Forty-one consecutive patients underwent
      simultaneous mandibular and maxillary osteotomy. Whole blood samples were
      collected preoperatively. The intraoperative blood loss volume was precisely
      estimated. The viscoelastic properties of whole blood samples were evaluated by
      thromboelastography (TEG), a global method that addresses the complex interplay
      among coagulation factors, blood platelets, and components of the fibrinolytic
      system. Blood platelet count, activated partial thromboplastin time, prothrombin
      time, plasma fibrinogen concentration, and D-dimer concentration were determined
      by routine methods. RESULTS: Patients were separated into 2 groups according to
      their intraoperative bleeding volume (<= 400 mL and >400 mL). No significant
      associations were observed between routine coagulation tests and intraoperative
      bleeding volume. The TEG results for the groups were compared. Significant
      associations were observed between intraoperative blood loss and the clot
      formation time, maximum clot firmness, and alpha angle, whereas bleeding volume
      was not related to the fibrinolytic resistance of the blood clot. An alpha angle
      exceeding 67 degrees  predicted with 95% certainty a blood loss of 400 mL or
      less. CONCLUSIONS: We conclude that intraoperative bleeding volume in patients
      subjected to orthognathic surgery can be predicted by means of preoperative TEG
      analysis. TEG results provide optimization of patient safety and can be used for
      the evaluation of bleeding risk.

PMID- 22990101
TI  - A more accurate method of predicting soft tissue changes after mandibular setback
      surgery.
AB  - PURPOSE: To propose a more accurate method to predict the soft tissue changes
      after orthognathic surgery. PATIENTS AND METHODS: The subjects included 69
      patients who had undergone surgical correction of Class III mandibular
      prognathism by mandibular setback. Two multivariate methods of forming prediction
      equations were examined using 134 predictor and 36 soft tissue response
      variables: the ordinary least-squares (OLS) and the partial least-squares (PLS)
      methods. After fitting the equation, the bias and a mean absolute prediction
      error were calculated. To evaluate the predictive performance of the prediction
      equations, a 10-fold cross-validation method was used. RESULTS: The multivariate
      PLS method showed significantly better predictive performance than the
      conventional OLS method. The bias pattern was more favorable and the absolute
      prediction accuracy was significantly better with the PLS method than with the
      OLS method. CONCLUSIONS: The multivariate PLS method was more satisfactory than
      the conventional OLS method in accurately predicting the soft tissue profile
      change after Class III mandibular setback surgery.

PMID- 22990102
TI  - Reducing emergency admissions: are we on the right track?

PMID- 22990103
TI  - Is there equal pay in healthcare? Not if you are a doctor.

PMID- 22990104
TI  - Measuring exhaled nitric oxide in animal models: methods and clinical
      implications.
AB  - Animal models such as rats and mice are useful for studying the multiple roles of
      nitric oxide (NO) in various respiratory disorders. The production of NO is
      catalyzed by the three isoforms of the enzymes (NO synthases; NOS). Indirect
      assessment of NOS gene or protein expression only provides partial information on
      the role of NO in health and lung disease. NO can also be measured in exhaled air
      by invasive or non-invasive approaches as a direct and quantitative marker of NO
      production in animal models. Whilst addressing the different methods of exhaled
      NO analysis in small animals (rats and mice), this review also focuses on the
      possible clinical implications, and discusses the advantages and limitations of
      these methods.

PMID- 22990105
TI  - Identification of differentially expressed proteins from primary versus
      metastatic pancreatic cancer cells using subcellular proteomics.
AB  - Pancreatic cancer is an aggressive disease with nearly equal yearly rates of
      diagnosis and death. Current therapies have failed to improve outcomes due to
      rapid disease progression and late stage at presentation. Recently, pathways
      involved in progression and metastasis have been elucidated; however, new
      knowledge has not generated more effective therapies. We report on the use of
      subcellular fractionation and liquid chromatography (LC)-mass spectrometry to
      identify 3,907 proteins in four pancreatic cancer cell lines, 540 of which are
      unique to primary cancer cells, and 487 unique to cells derived from metastatic
      sites. Statistical analysis identified 134 proteins significantly differentially
      expressed between the two populations. The subcellular localization of these
      proteins was determined and expression levels for four targets were validated
      using western blot techniques. These identified proteins can be further
      investigated to determine their roles in progression and metastasis and may serve
      as therapeutic targets in the development of more effective treatments for
      pancreatic cancer.

PMID- 22990106
TI  - Identification of markers associated with highly aggressive metastatic phenotypes
      using quantitative comparative proteomics.
AB  - BACKGROUND: The spread of cancer cells from a primary tumor to form metastases at
      distant sites is a complex process that remains poorly defined. Certain tumor
      cells are more aggressive and thus lead to rapid development of multiple distant
      metastases. Here, we identify proteins associated with these aggressive
      phenotypes. MATERIALS AND METHODS: To identify proteins associated with cancer
      cell aggressiveness, we used comparative, quantitative liquid chromatography
      tandem mass spectrometry (LC-MS/MS) proteome analysis of a unique metastasis
      model comprised of three isogenic human breast cancer cell lines that are equally
      tumorigenic in mice, but display different metastatic potentials ranging from non
      metastatic, intermediate-metastatic and highly-metastatic. The altered expression
      of selected proteins was subsequently confirmed by immunocyto- and
      immunohistochemistry. RESULTS: The difference in metastatic capabilities was
      initially confirmed using live animal imaging. Comparative, quantitative
      proteomics identified 414 proteins, out of which 44 exhibited altered expression
      between the metastatic and non-metastatic cell lines. The proteins correlating
      with the aggressiveness of metastasis included leucine-rich repeat containing 59
      (LRRC59), while CD59 and chondroitin sulfate proteoglycan 4 (CSPG4) exhibited an
      inverse correlation with metastatic capability. The altered expression levels of
      these proteins were biochemically confirmed, as well as demonstrated in
      xenografts generated from these cell lines. This analysis further demonstrated
      that the three proteins were associated with the aggressiveness of metastasis
      rather than metastasis colonization per se. CONCLUSION: Our study provides novel
      insights into key proteins associated with the metastatic potential of breast
      cancer cells and identified LRRC59, CD59 and CSPG4 as candidates that merit
      further study.

PMID- 22990107
TI  - Are we missing the target? Cancer stem cells and drug resistance in non-small
      cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death
      in Western countries. Despite novel molecular therapies, the majority of patients
      with advanced or metastatic disease show rapid progression and a median survival
      time of not more than 18 months. In the last decade, there has been increasing
      evidence that cancer stem cells (CSC) play a pivotal role in drug resistance,
      tumour regeneration and metastasis of various cancer entities including lung
      cancer. In this review, we discuss the evidence for stem cells in NSCLC, their
      predictive and prognostic significance, their specific mechanisms of resistance
      and potential targets and strategies for eradication of these cells.
      Consideration of the specific properties of CSC in lung cancer therapy might
      substantially contribute to increased response and prolonged survival rates in
      this disease.

PMID- 22990108
TI  - Single nucleotide polymorphisms of genes for EGF, TGF-beta and TNF-alpha in
      patients with pancreatic carcinoma.
AB  - AIM: To show whether single nucleotide polymorphisms (SNPs) of Epidermal growth
      factor (EGF)-61(*)A/G, Transforming growth factor beta 1 (TGF-B1) - 509(*)T/C and
      Tumor necrosis factor-alpha (TNF-A) -308(*)A/G are associated with the survival
      rate after pancreatic cancer surgery and with the frequency of post-operative
      complications. PATIENTS AND METHODS: EGF 61(*)A/G, TGF-B1-509(*)T/C and TNF-A
      308(*)A/G genotypes were analyzed in patients who underwent pylorus-preserving
      pancreaticoduonectomy for pancreatic carcinoma and were determined by means of
      Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
      The association of each genetic polymorphism with clinical and pathological data
      of the patients and early tumor recurrence were evaluated. RESULTS: A
      significantly lower median survival duration was found in EGF 61(*)AA
      homozygotes, as compared to the AG heterozygous group. There was also a
      significantly lower median survival duration in the TNF-A-308(*) AA homozygote
      group as compared to the AG and GG groups. Survival duration in patients had no
      correlation with TGF-B1 -509(*)T/C polymorphism. There was a significantly lower
      median survival duration in the TNF-A -308(*) AA homozygous group, as compared to
      the AG and GG group in a Cox proportional hazard model. The frequency of the TGF
      B1 T-allele was higher among patients with leakage of the pancreatic anastomosis.
      The frequency of the TGF-B1 TC genotype was significantly higher among patients
      who developed leakage of the biliodigestive anastomosis as compared with the TGF
      B1 CC genotype. The frequency of TGF-B1 T-carriers (i.e. TT+TC) was significantly
      higher among patients with leakage of the biliodigestive anastomosis, as compared
      to these with the TGF-B1 CC genotype. In a Cox proportional hazard model, only
      wound infection had a significant correlation with long-term survival duration of
      patients with pancreatic cancer. CONCLUSION: There appears to be a significant
      correlation of the EGF-61(*) AA and of the TNF-A -308(*) AA polymorphism with
      lower survival duration in patients with resectable pancreatic carcinoma. The
      presence of wound infection was associated with poor prognosis. TGF-B1-509(*) T
      carrying genotypes were more frequent in paitents with severe post-operative
      complications.

PMID- 22990109
TI  - Breast cancer and metastasis: on the way toward individualized therapy.
AB  - Breast cancer (BC) remains the most common cancer type diagnosed in women.
      Although targeted therapies have improved patient survival for advanced BC, these
      tumors frequently relapse due to drug resistance mechanisms. A systems biology
      approach integrates DNA, RNA and protein alterations generated from
      multidimensional platforms to better understand the mechanisms that regulate the
      metastatic process. Downstream functional analyses in pre-clinical studies might
      integrate the role of these aberrations into the cell, leading to discovery of
      new therapeutic targets. In the present report, we review relevant findings
      associated with genomic, transcriptomic and proteomic analyses and the
      contribution of the systems biology concept to the interpretation of these data
      in the metastatic context. Also, we highlight the importance of re-designing
      clinical trials towards metastasis prevention for improvement of personalized
      care.

PMID- 22990110
TI  - Breast cancer metastasis.
AB  - Breast cancer metastasis accounts for the majority of deaths from breast cancer.
      Detection of breast cancer metastasis at the earliest stage is important for the
      management and prediction of breast cancer progression. Emerging techniques using
      the analysis of circulating tumor cells show promising results in predicting and
      identifying the early stages of breast cancer metastasis in patients.
      Additionally, a deeper understanding of the metastatic cascade in breast cancer
      will be critical for developing therapeutic interventions to combat breast cancer
      metastasis. In this review, the current and novel methods for detection of breast
      cancer metastasis, as well as the mechanisms involved in metastasis and the
      treatment of breast cancer metastasis, are discussed.

PMID- 22990111
TI  - Expression of signal-induced proliferation-associated gene 1 (SIPA1), a RapGTPase
      activating protein, is increased in colorectal cancer and has diverse effects on
      functions of colorectal cancer cells.
AB  - BACKGROUND: Signal-induced proliferation-associated gene 1 (SIPA1) codes for a
      GTPase-activating protein, known to be a negative regulator of Ras-related
      Protein (RAP) which belongs to the Ras superfamily. It has been implicated in
      certain malignancies, including leukemia, cervical cancer and breast cancer.
      However the role of this molecule in colorectal cancer remains unknown. The
      current study aimed to investigate the expression of SIPA1 in colorectal tumour
      tissues and its impact on the function of colorectal cancer cells. MATERIALS AND
      METHODS: A total of 94 colorectal cancer tissues together with 80 normal
      background tissues were used to examine the expression of SIPA1 transcript and
      protein using real-time quantitative Polymerase Chain Reaction (PCR) and
      immunohistochemical methods, respectively. Any association with clinical and
      histopathological characteristics was then identified. Ribozyme transgenes
      targeting SIPA1 were prepared to knockdown the expression of SIPA1 in colorectal
      cancer cells. The impact on their functions was subsequently determined, using
      respective in vitro function assays. RESULTS: An increased expression of SIPA1
      was evident in colorectal cancer tissues compared with its expression in normal
      background tissues (p<0.001). In colorectal tumours, its expression appeared to
      be lower in poorly-differentiated samples and in patients who had lymphatic
      metastasis. Knockdown of SIPA1 in colorectal cancer cells resulted in reduced
      cell growth in vitro. The knockdown exhibited a contrasting effect on invasion
      and migration, both of which were increased in SIPA1-knockdown cells compared
      with the controls. CONCLUSION: SIPA1 is up-regulated in colorectal cancer. This
      suggests that SIPA1 plays diverse roles during disease progression as has
      contrasting effects on growth and motility of colorectal cancer cells.

PMID- 22990112
TI  - Metastasis from oral cancer: an overview.
AB  - Oral cancer is a common neoplasm worldwide. Its incidence and mortality have also
      increased over the past decades. It is characterized by poor prognosis and a low
      survival rate despite sophisticated surgical and radiotherapeutic modalities.
      Metastasis of oral cancer is a complex process involving detachment of cells from
      tumor tissue, regulation of cell motility and invasion, proliferation and evasion
      through the lymphatic system or blood vessels. In this review, we will focus on
      the current knowledge in metastasis from oral cancer regarding facts, such as
      incidence; stage, histopathology and grade of primary tumor; clinical
      manifestations; diagnosis; and treatment. Certainly, such information will
      contribute to the understanding of oral cancer pathogenesis.

PMID- 22990113
TI  - KRAS testing in clinical laboratory: optimizing targeted therapy.
AB  - BACKGROUND/AIM: Activating mutations in the KRAS gene are found in more than 30%
      of colorectal tumors, where they are associated with a poor response to anti
      epidermal growth factor receptor therapies. Mutation testing techniques have
      therefore become an urgent concern. Several methods for KRAS mutation detection
      have been described in the literature. Most of these are laboratory developed
      tests and only a few commercial assays are currently available. MATERIALS AND
      METHODS: We studied the performance characteristics of a KRAS mutation detection
      assay on the ABI-3130XL genetic analyzer using a new commercial mutation
      detection kit based on shifted termination assay technology. Samples were
      analyzed in parallel by different reference laboratories using alternative
      methodologies. Various sample types were used including formalin-fixed paraffin
      embedded tissue, fine-needle aspirates, and cyst fluid specimens. RESULTS: A high
      level of agreement (100% correlation for formalin-fixed paraffin-embedded tissue
      and fine-needle aspirate samples and 93% correlation for cyst fluid specimens)
      was obtained despite the use of different methodologies. CONCLUSION: Shift
      termination assay is a simple, robust, and sensitive method for the
      identification of KRAS mutations in a wide variety of specimen types.

PMID- 22990116
TI  - Modulating mitochondrial intracellular location as a redox signal.
AB  - Mitochondria have various essential functions in metabolism and in determining
      cell fate during apoptosis. In addition, mitochondria are also important nodes in
      a number of signaling pathways. For example, mitochondria can modulate signals
      transmitted by second messengers such as calcium. Because mitochondria are also
      major sources of reactive oxygen species (ROS), they can contribute to redox
      signaling--for example, by the production of ROS such as hydrogen peroxide that
      can reversibly modify cysteine residues and thus the activity of target proteins.
      Mitochondrial ROS production is thought to play a role in hypoxia signaling by
      stabilizing the oxygen-sensitive transcription factor hypoxia-inducible factor
      1alpha. New evidence has extended the mechanism of mitochondrial redox signaling
      in cellular responses to hypoxia in interesting and unexpected ways. Hypoxia
      altered the microtubule-dependent transport of mitochondria so that the
      organelles accumulated in the perinuclear region, where they increased the
      intranuclear concentration of ROS. The increased ROS in turn enhanced the
      expression of hypoxia-sensitive genes such as VEGF (vascular endothelial growth
      factor) not by reversibly oxidizing a protein, but by oxidizing DNA sequences in
      the hypoxia response element of the VEGF promoter. This paper and other recent
      work suggest a new twist on mitochondrial signaling: that the redistribution of
      mitochondria within the cell can be a component of regulatory pathways.

PMID- 22990115
TI  - Long-term and stable correction of uremic anemia by intramuscular injection of
      plasmids containing hypoxia-regulated system of erythropoietin expression.
AB  - Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is
      a major cause of renal anemia. This study planned to investigate whether the
      hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the
      chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in
      combination with cytomegalovirus immediate- early (CMV IE) basal gene promoter
      and delivered by plasmid intramuscular injection, might provide a long-term
      physiologically regulated Epo secretion expression to correct the anemia in
      adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by
      fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this
      promoter was evaluated first in vitro and then in vivo in healthy and uremic rats
      (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed
      by a constitutive CMV gene promoter served as control. ANOVA and Student's t-test
      were used to analyze between- group differences. A high-level expression of Epo
      was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo
      corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal
      (P < 0.05), but that of the pHRE-Epo-treated rats didn't. Hypoxia-regulated
      system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter
      and delivered by plasmid intramuscular injection may provide a long-term and
      stable Epo expression and secretion in vivo to correct the anemia in adenine
      induced uremic rats.

PMID- 22990117
TI  - Pseudogenes: newly discovered players in human cancer.
AB  - Because they are generally noncoding and thus considered nonfunctional and
      unimportant, pseudogenes have long been neglected. Recent advances have
      established that the DNA of a pseudogene, the RNA transcribed from a pseudogene,
      or the protein translated from a pseudogene can have multiple, diverse functions
      and that these functions can affect not only their parental genes but also
      unrelated genes. Therefore, pseudogenes have emerged as a previously
      unappreciated class of sophisticated modulators of gene expression, with a
      multifaceted involvement in the pathogenesis of human cancer.

PMID- 22990119
TI  - Effect of training status on immune defence related gene expression in
      Thoroughbred: are genes ready for the sprint?
AB  - Athletic performance is both a stress factor and an adaptive response to exercise
      that may be modulated by training, reduce inflammation and help prevent disease.
      Studies on the endocrinology of exercise and training have demonstrated the
      existence of an integrated metabolic network of hormone and cytokine regulation.
      Subsequent molecular studies have shown that repeated bouts of exercise may
      establish new basal levels of gene expression at rest. The Thoroughbred horse may
      be a useful 'exercise model' for inter-individual comparisons between subjects
      with homogeneous genetic and environmental backgrounds and similar exercise
      management practices. In this study, the effects of training and acute effort on
      gene expression were evaluated with a real time PCR approach in athletic (n=10)
      and sedentary horses (n=9), using a previously characterised panel of genes known
      to be highly modulated during effort (CXCL2, TLR4, IL1beta, IL8, IL1RII, IL18,
      IL6 and CEBPbeta). A 'rest comparison' was performed to evaluate a training
      effect in both groups while a 'race comparison' was performed in athletic horses
      only (before, immediately after, and 12h after racing) to determine the effect of
      acute effort. The results indicated that many of the investigated genes (TLR4,
      IL1beta, IL1RII, IL18, IL6 and CEBPbeta) were expressed to a greater extent in
      athletic horses compared to sedentary animals when both were at rest. However, a
      time-course comparison in the athletic horses revealed that genes exhibiting the
      highest levels of expression at rest did not show significant changes after the
      race. The findings suggested that training may exert a conditioning on gene
      expression at rest leading to a more prompt response to exercise-induced stress
      in Thoroughbreds.

PMID- 22990120
TI  - Uncertainty in mammary cancer outcomes: comparative oncology to the rescue!

PMID- 22990118
TI  - Charting the landscape of tandem BRCT domain-mediated protein interactions.
AB  - Eukaryotic cells have evolved an intricate system to resolve DNA damage to
      prevent its transmission to daughter cells. This system, collectively known as
      the DNA damage response (DDR) network, includes many proteins that detect DNA
      damage, promote repair, and coordinate progression through the cell cycle.
      Because defects in this network can lead to cancer, this network constitutes a
      barrier against tumorigenesis. The modular BRCA1 carboxyl-terminal (BRCT) domain
      is frequently present in proteins involved in the DDR, can exist either as an
      individual domain or as tandem domains (tBRCT), and can bind phosphorylated
      peptides. We performed a systematic analysis of protein-protein interactions
      involving tBRCT in the DDR by combining literature curation, yeast two-hybrid
      screens, and tandem affinity purification coupled to mass spectrometry. We
      identified 23 proteins containing conserved BRCT domains and generated a human
      protein-protein interaction network for seven proteins with tBRCT. This study
      also revealed previously unknown components in DNA damage signaling, such as
      COMMD1 and the target of rapamycin complex mTORC2. Additionally, integration of
      tBRCT domain interactions with DDR phosphoprotein studies and analysis of kinase
      substrate interactions revealed signaling subnetworks that may aid in
      understanding the involvement of tBRCT in disease and DNA repair.

PMID- 22990121
TI  - Sugar expression in the mucosae of the canine uterus and vagina during the
      oestrous cycle and with pyometra.
AB  - The pathogenesis of canine pyometra is still unclear, but bacterial infection of
      the endometrium, mediated by bacterial lectins, is suspected to induce pyometra.
      The aim of this study was to investigate sugar expression in the mucosae of the
      uterus and vagina of healthy dogs with normal oestrous cycles and in dogs with
      pyometra, using a panel of lectins to investigate the pathogenesis of pyometra.
      In dogs with pyometra, the uterine and vaginal mucosae were positive for lectins
      that selectively bind to glucose or mannose, especially during days 7-10 and 30
      40 of dioestrus. These results suggest that temporal changes in sugar expression
      in the uterus and vagina present an opportunity for pathogens to infect the
      endometrium, causing pyometra.

PMID- 22990122
TI  - In vivo femorotibial subluxation during weight-bearing and clinical outcome
      following tibial tuberosity advancement for cranial cruciate ligament
      insufficiency in dogs.
AB  - Ex vivo studies have been used extensively to investigate the mechanisms of
      tibial osteotomies but few have explored femorotibial alignment in vivo. The aim
      of this study was to assess femorotibial joint alignment under static weight
      bearing conditions (and subsequent outcome) in dogs treated for cranial cruciate
      ligament (CrCL) insufficiency with tibial tuberosity advancement (TTA). Twenty
      five dogs (30 stifles) with CrCL insufficiency treated by TTA were included. The
      distance from the origin to insertion of the CrCL (CrCLd) was measured on non
      weight-bearing immediate post-operative radiographs and weight-bearing follow-up
      radiographs. CrCLd values were compared using a paired t test. The relationship
      between change in CrCLd (DeltaCrCLd) and post-operative patellar tendon angle
      according to the common tangent method (PTACT) was assessed using Pearson's
      correlation. Outcome was assessed with an owner-completed questionnaire, and peak
      vertical force (PVF) and vertical impulse (VI) as percentages of bodyweight (BW).
      Following TTA, 21/30 stifles were persistently subluxated at a follow-up of 18 +/
      14 months (mean +/- SD). Follow-up weight-bearing CrCLd was greater (P<0.001)
      than post-operative non-weight-bearing CrCLd, with a mean DeltaCrCLd of 5.8 +/-
      3.4mm (16 +/- 10%). Post-operative PTACT was 89 +/- 3 degrees  and did not
      correlate with DeltaCrCLd (r=0.002, P=0.994). Mean PVF and VI were 65 +/- 10% BW
      and 9+/-2% BW, respectively. All owners felt TTA provided improvement in
      lameness. The results indicated that TTA does not normalize sagittal plane
      femorotibial stability during standing at a PTACT of 90 degrees , but most dogs
      return to good limb function regardless of femorotibial alignment.

PMID- 22990123
TI  - A forensic investigation of Mycobacterium bovis infection in badgers.

PMID- 22990124
TI  - Mesoporous systems for poorly soluble drugs.
AB  - Utilization of inorganic mesoporous materials in formulations of poorly water
      soluble drugs to enhance their dissolution and permeation behavior is a rapidly
      growing area in pharmaceutical materials research. The benefits of mesoporous
      materials in drug delivery applications stem from their large surface area and
      pore volume. These properties enable the materials to accommodate large amounts
      of payload molecules, protect them from premature degradation, and promote
      controlled and fast release. As carriers with various morphologies and chemical
      surface properties can be produced, these materials may even promote adsorption
      from the gastrointestinal tract to the systemic circulation. The main concern
      regarding their clinical applications is still the safety aspect even though most
      of them have been reported to be safely excreted, and a rather extensive toxicity
      screening has already been conducted with the most frequently studied mesoporous
      materials. In addition, the production of the materials on a large scale and at a
      reasonable cost may be a challenge when considering the utilization of the
      materials in industrial processes. However, if mesoporous materials could be
      employed in the industrial crystallization processes to produce hybrid materials
      with poorly soluble compounds, and hence to enhance their oral bioavailability,
      this might open new avenues for the pharmaceutical industry to employ
      nanotechnology in their processes. 

PMID- 22990128
TI  - Nickel(II) complexes of the new pincer-type unsymmetrical ligands PIMCOP,
      PIMIOCOP, and NHCCOP: versatile binding motifs.
AB  - Chelation/nickellation of an unsymmetrical meta-phenylene-based ligand featuring
      phosphinite and imidazolophosphine functionalities gives the corresponding pincer
      complex. N-Methylation of the latter generates a new complex featuring the
      ternary moiety NHC->Ph(2)P(+)->Ni, which can be converted subsequently into the
      binary moiety NHC->Ni by extrusion of Ph(2)P(+), thus allowing a sequential
      synthesis of pincer complexes displaying varying degrees of dipolar character.

PMID- 22990129
TI  - Differential molecular mechanism of docetaxel-octreotide combined treatment
      according to the docetaxel-resistance status in PC3 prostate cancer cells.
AB  - To examine the effect and the molecular mechanisms of the combined treatment of
      the somatostatin (SST) analogue octreotide with docetaxel: analysis of
      proliferation, apoptosis and migration in the human prostate cancer cell line
      PC3, either sensitive (PC3wt) or made resistant to docetaxel (PC3R). We examined
      the effect of the two drugs individually or in combination on cell proliferation
      and migration by analysis of apoptosis and cell cycle proteins. The role of
      octreotide in modulating P-glycoprotein function was examined together with the
      modulation of SST receptors type 2 and 5 (SSTR2 and SSTR5). We observed an
      enhanced effect of docetaxel and octreotide given in combination or in sequence
      compared with either agent alone; this result was particularly evident when
      docetaxel was given before octreotide in PC3wt and when the two drugs were given
      together in PC3R cells. In contrast to lanreotide, our data indicate that
      octreotide does not act as a P-glycoprotein inhibitor in PC3R cells. A role of
      docetaxel and combined treatment in regulating SSTR2, SSTR5, proliferation and
      apoptosis gene expression is suggested as the possible mechanism for the enhanced
      effect observed. In addition, an evaluation of the effect of the combined
      treatment on cellular migration was examined, showing a moderate loss of invasive
      properties in PC3R cells. The present results confirm that SST analogues may be
      combined with docetaxel to increase the antitumour effect in patients with
      advanced prostate carcinoma.

PMID- 22990130
TI  - A functionalized poly(amidoamine) nanocarrier-loading 5-fluorouracil:  pH
      responsive drug release and enhanced anticancer effect.
AB  - A functionalized poly(amidoamine) (PAMAM) nanocarrier was designed and prepared
      to deliver anticancer drugs. The nanocarrier is a copolymer with a core-shell
      structure with 3.0 G PAMAM as the core and sequentially conjugated poly(2-(N,N
      diethylamino)ethyl methacrylate) (pDEA) and methoxy-poly(ethylene glycol) 2000
      (mPEG) as the shell. The copolymer, PAMAM-pDEA-mPEG, was synthesized using atom
      transfer radical polymerization and click chemistry. The PAMAM core loaded drugs.
      pDEA had pH-sensitive properties, showing hydrophobicity in neutral environments
      and hydrophilicity in weakly acidic environments because of the presence of
      tertiary amines. Therefore, pDEA was a functional layer coating drugs in neutral
      environments and releasing drugs in acidic environments. The outer mPEG layer
      allowed the nanocarrier to circulate in the blood for a long period of time and
      improved the stability of the nanocarriers. The anticancer drug 5-fluorouracil (5
      FU) was entrapped in the nanocarrier at high levels by changing the pH from 4.0
      to 8.0. The drug release was also highly pH responsive, and the release rate was
      much higher at pH 6.5 than at pH 7.4, which favored drug release in the weakly
      acidic tumor environment. The blank nanocarrier was not toxic to cells or
      animals. The 5-FU-loaded nanocarrier exerted enhanced anticancer effects on tumor
      bearing mice relative to 5-FU alone. PAMAM-pDEA-mPEG is a promising nanocarrier
      for the delivery of anticancer drugs.

PMID- 22990131
TI  - Measurement of the giant magnetoresistance effect in cobalt-silver magnetic
      nanostructures: nanoparticles.
AB  - Cobalt-silver (Co-Ag) core-shell nanoparticles with different silver thicknesses
      were prepared by the microemulsion method in a two-step reduction process.
      Transmission electron microscopy (TEM) characterization revealed the almost
      monodispersity and nanometric size (in the range 3-5 nm depending on the shell
      thickness) of the synthesized nanoparticles. However, it was the use of high
      resolution TEM that revealed the correct core-shell formation of the nanometric
      material. The selected area electron diffraction pattern indicated the fcc (face
      centered cubic) and hcp (hexagonal close packed) nature for silver and cobalt,
      respectively. Cyclic voltammetry also allowed the correct core-shell formation to
      be assured. The magnetic properties revealed the presence of both
      superparamagnetic and ferromagnetic contributions. Because of the lack of
      methodology, it was necessary to develop a method to measure the magnetotransport
      properties of the prepared nanoparticles. The strategy which followed was
      successful as it was possible to measure these properties: giant
      magnetoresistance values of 0.1% at room temperature were obtained. The numerical
      analysis of magnetic and magnetoresistance data indicated the presence of
      superparamagnetic particles showing interaction among the magnetic moments.

PMID- 22990132
TI  - Acute haemodynamic effects of inhaled nitric oxide in premature infants with mild
      to-moderate respiratory distress.

PMID- 22990133
TI  - Acropustulosis of infancy.

PMID- 22990134
TI  - Outcome of infants presenting with echogenic bowel in the second trimester of
      pregnancy.
AB  - OBJECTIVE: Fetal echogenic bowel (FEB) is a soft marker found on second trimester
      sonography. Our main aim was to determine the outcome of infants who presented
      with FEB and secondarily to identify additional sonographic findings that might
      have clinical relevance for the prognosis. DESIGN: We reviewed all pregnancies in
      which the diagnosis FEB was made in our Fetal Medicine Unit during 2009-2010
      (N=121). We divided all cases into five groups according to additional
      sonographic findings. Group 1 consisted of cases of isolated FEB, group 2 of FEB
      associated with dilated bowels, group 3 of FEB with one or two other soft
      markers, group 4 of FEB with major congenital anomalies or three or more other
      soft markers, and group 5 consisted of FEB with isolated intrauterine growth
      restriction (IUGR). RESULTS: Of 121 cases, five were lost to follow-up. Of the
      remaining 116 cases, 48 (41.4%) were assigned to group 1, 15 (12.9%) to group 2,
      15 (12.9%) to group 3, 27 (23.2%) to group 4, and 11 (9.5%) to group 5. The
      outcome for group 1 was uneventful. In group 2 and 3, two anomalies, anorectal
      malformation and cystic fibrosis, were detected postnatally (6.7%). In group 4,
      mortality and morbidity were high (78% resp. 22%). Group 5 also had high
      mortality (82%) and major morbidity (18%). CONCLUSIONS: If FEB occurs in
      isolation, it is a benign condition carrying a favourable prognosis. If multiple
      additional anomalies or early IUGR are observed, the prognosis tends to be less
      favourable to extremely poor.

PMID- 22990135
TI  - Quantitative structure-activity relationships for organophosphates binding to
      acetylcholinesterase.
AB  - Organophosphates are a group of pesticides and chemical warfare nerve agents that
      inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the
      excitatory neurotransmitter acetylcholine. Numerous structural variants exist for
      this chemical class, and data regarding their toxicity can be difficult to obtain
      in a timely fashion. At the same time, their use as pesticides and military
      weapons is widespread, which presents a major concern and challenge in evaluating
      human toxicity. To address this concern, a quantitative structure-activity
      relationship (QSAR) was developed to predict pentavalent organophosphate oxon
      human acetylcholinesterase bimolecular rate constants. A database of 278 three
      dimensional structures and their bimolecular rates was developed from 15 peer
      reviewed publications. A database of simplified molecular input line entry
      notations and their respective acetylcholinesterase bimolecular rate constants
      are listed in Supplementary Material, Table I. The database was quite diverse,
      spanning 7 log units of activity. In order to describe their structure, 675
      molecular descriptors were calculated using AMPAC 8.0 and CODESSA 2.7.10.
      Orthogonal projection to latent structures regression, bootstrap leave-random
      many-out cross-validation and y-randomization were used to develop an externally
      validated consensus QSAR model. The domain of applicability was assessed by the
      William's plot. Six external compounds were outside the warning leverage
      indicating potential model extrapolation. A number of compounds had residuals >2
      or <-2, indicating potential outliers or activity cliffs. The results show that
      the HOMO-LUMO energy gap contributed most significantly to the binding affinity.
      A mean training R (2) of 0.80, a mean test set R (2) of 0.76 and a consensus
      external test set R (2) of 0.66 were achieved using the QSAR. The training and
      external test set RMSE values were found to be 0.76 and 0.88. The results suggest
      that this QSAR model can be used in physiologically based
      pharmacokinetic/pharmacodynamic models of organophosphate toxicity to determine
      the rate of acetylcholinesterase inhibition.

PMID- 22990136
TI  - Chemical dispersant potentiates crude oil impacts on growth, reproduction, and
      gene expression in Caenorhabditis elegans.
AB  - The economic, environmental, and human health impacts of the deepwater horizon
      (DWH) oil spill have been of significant concern in the general public and among
      scientists. This study employs parallel experiments to test the effects of crude
      oil from the DWH oil well, chemical dispersant Corexit 9500A, and dispersant-oil
      mixture on growth and reproduction in the model organism Caenorhabditis elegans.
      Both the crude oil and the dispersant significantly inhibited the reproduction of
      C. elegans. Dose-dependent inhibitions of hatched larvae production were observed
      in worms exposed to both crude oil and dispersant. Importantly, the chemical
      dispersant Corexit 9500A potentiated crude oil effects; dispersant-oil mixture
      induced more significant effects than oil or dispersant-alone exposures. While
      oil-alone exposure and dispersant-alone exposure have none to moderate inhibitory
      effects on hatched larvae production, respectively, the mixture of dispersant and
      oil induced much more significant inhibition of offspring production. The
      production of hatched larvae was almost completely inhibited by several high
      concentrations of the dispersant-oil mixture. This suggests a sensitive bioassay
      for future investigation of oil/dispersant impacts on organisms. We also
      investigated the effects of crude oil/dispersant exposure at the molecular level
      by measuring the expressions of 31 functional genes. Results showed that the
      dispersant and the dispersant-oil mixture induced aberrant expressions of 12
      protein-coding genes (cat-4, trxr-2, sdhb-1, lev-8, lin-39, unc-115, prdx-3, sod
      1, acr-16, ric-3, unc-68, and acr-8). These 12 genes are associated with a
      variety of biological processes, including egg-laying, oxidative stress, muscle
      contraction, and neurological functions. In summary, the toxicity potentiating
      effect of chemical dispersant must be taken into consideration in future crude
      oil cleanup applications.

PMID- 22990137
TI  - Polymorphisms hit the headlines.

PMID- 22990139
TI  - Boron-doped carbon nanotube-supported Pt nanoparticles with improved CO tolerance
      for methanol electro-oxidation.
AB  - Boron doping into carbon nanotubes improves the CO tolerance and increases the
      utilization efficiency of the supported Pt nanoparticles. Boron doping leads to a
      uniform deposition of Pt nanoparticles and also facilitates the removal of CO
      from the Pt surface, resulting in an increase in the electrocatalytic activity
      for methanol oxidation.

PMID- 22990138
TI  - Impact of rapid drug susceptibility testing for tuberculosis: program experience
      in Lima, Peru.
AB  - SETTING: Programmatic implementation of decentralized rapid drug susceptibility
      testing (DST) in Lima, Peru. OBJECTIVE: Pre-post analysis compared time to
      diagnosis, treatment outcome and survival among patients tested with direct
      nitrate reductase assay (NRA) vs. indirect conventional  methods. DESIGN: From
      2005 to 2009, we prospectively followed all patients referred for DST before
      (control) and after (intervention) NRA implementation. Among those referred for
      DST, NRA was used for smear-positive samples of patients with no prior history of
      multidrug resistance or treatment  for multidrug-resistant tuberculosis (TB).
      Data were abstracted from patient charts and laboratory registers. Endpoints were
      favorable outcomes, time to result and time to death. RESULTS: Of those patients
      who met the criteria for NRA, 740 underwent NRA and 621 underwent conventional
      DST.  NRA yielded test results for 78.4% of cases vs. 68.8% for conventional DST
      (P < 0.0001); the median time to result was 44 vs. 133 days, respectively
      (adjusted HR 0.64, 95%CI 0.56-0.73). Among individuals without previous anti
      tuberculosis treatment, NRA was associated with  a favorable treatment outcome
      (adjusted OR 1.39, 95%CI 1.01-1.90) and prolonged survival (adjusted HR 0.53,
      95%CI 0.31-0.90). CONCLUSION: Direct NRA significantly shortened time to test
      result and improved treatment outcomes and survival in certain groups.

PMID- 22990140
TI  - Microenvironment-mediated reversion of epiblast stem cells by reactivation of
      repressed JAK-STAT signaling.
AB  - Embryonic stem cells (ESC) and epiblast stem cells (EpiSC) are distinct
      pluripotent stem cell states that require different signaling pathways for their
      self-renewal. Forward transitions between ESC and EpiSC can be accomplished by
      changing culture conditions; however reverse transitions between EpiSC and ESC
      are rare events that require transgene insertion or culture on feeders. We
      demonstrate that transgene-free reversion of EpiSCs to ESCs can be enhanced by
      local microenvironmental control and the subsequent reactivation of dormant LIF
      STAT3 signaling. Reactivation of LIF responsiveness occurs in regions of colony
      constraint (high local cell density) typical of culture on feeders, a condition
      that can be recapitulated using micropatterned (MUP) colonies under defined
      conditions. This increased LIF responsiveness results in a subsequent increase in
      the frequency of EpiSC reversion. Importantly, the resulting revertant EpiSCs are
      functionally indistinguishable from naive mESC. Our findings demonstrate that
      signaling pathway activation and repression create barriers to cell fate
      transitions that can be overcome by microenvironmental control.

PMID- 22990141
TI  - Efficacy, tolerability, compliance, and quality of life of patients with mood
      disorders switched from quetiapine immediate release to extended release.
AB  - The present study aimed to assess switch from immediate-release (IR) to extended
      release (XR) quetiapine in terms of efficacy, tolerability, compliance, and
      quality of life in a sample of patients with mood disorders. Thirty patients, 10
      with major depressive disorder and 20 with bipolar disorder, with residual
      depressive symptoms, who had switched from quetiapine IR (mean 365 mg/day) to XR
      (mean 373 mg/day), were recruited and evaluated using different psychometric
      scales, administered at T0 (switch), T1, and T2 (1 and 6 weeks after the switch,
      respectively). A significant reduction from T0 to T2 of the total scores on the
      Hamilton depression rating scale (t=2.15; P=0.04), Hamilton anxiety scale
      (t=3.04; P=0.006), and clinical global impression-severity item (t=2.8; P=0.01)
      was found. No differences were found in terms of compliance and quality of life.
      The switch was well tolerated by 2/3 of patients. Most reported side effects were
      early/central insomnia with day drowsiness (16.7%), increased appetite and weight
      (8.4%), mild asthenia (4.2%), and constipation (4.2%), which, in two cases, led
      to switch interruption. Strategies to relieve side effects, including gradual
      cross-switch, improved switch feasibility. Switch from quetiapine IR to XR seems
      to be associated with clinical improvement in major depressives with residual
      symptoms, although some patients may report side effects because of the different
      pharmacokinetics.

PMID- 22990142
TI  - Adherence to escitalopram treatment in depression: a study of electronically
      compiled dosing histories in the 'Depression: the search for phenotypes' study.
AB  - Poor adherence to depression treatment is common. Understanding determinants of
      poor adherence to therapy is crucial to ensure optimal clinical outcomes. The aim
      of this study was to describe characteristics of dosing history in participants
      with depression receiving once daily escitalopram. Participants were randomly
      assigned to interpersonal psychotherapy (IPT) or pharmacotherapy. Participants
      assigned to IPT who did not evidence a response or remission had escitalopram
      added to their treatment. Adherence to pharmacotherapy was assessed using an
      electronically monitored pill cap (MEMS). Fifty-four participants on escitalopram
      alone and 32 on escitalopram+IPT were monitored. After 200 days, 71.7% of the
      participants in the escitalopram group and 54.8% of those in the escitalopram+IPT
      group were still engaged with the dosing regimen. Of those engaged in the dosing
      regimen, 17.9% (average over 210 days) of the participants did not take their
      medication (nonexecution). In 69% of the days participants took the correct
      dosage required. On average, participants had three drug holidays and the mean
      length of a holiday was 7 days per patient. No difference in adherence patterns
      was observed between patients receiving escitalopram alone vs. IPT+escitalopram.
      Early discontinuation of treatment and suboptimal daily execution of the
      prescribed regimen are the most common facets of poor adherence in this study
      population.

PMID- 22990143
TI  - A familial case of alveolar capillary dysplasia with misalignment of pulmonary
      veins supports paternal imprinting of FOXF1 in human.
AB  - Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a
      rare developmental lung disorder that is uniformly lethal. Affected infants die
      within the first few weeks of their life despite aggressive treatment, although a
      few cases of late manifestation and longer survival have been reported. We have
      shown previously that mutations and deletions in FOXF1 are a cause of this
      disorder. Although most of the cases of ACD/MPV are sporadic, there have been
      infrequent reports of familial cases. We present a family with five out of six
      children affected with ACD/MPV. DNA analysis identified a missense mutation
      (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected
      siblings tested. The same variant is also present as a de novo mutation in the
      mother and arose on her paternally derived chromosome 16. The two tested affected
      siblings share the same chromosome 16 haplotype inherited from their maternal
      grandfather. Their single healthy sibling has a different chromosome 16 haplotype
      inherited from the maternal grandmother. The results are consistent with paternal
      imprinting of FOXF1 in human.

PMID- 22990144
TI  - Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.
AB  - We report two children, born from consanguineous parents, who presented with
      early-onset refractory epilepsy associated with psychomotor delay, failure to
      thrive, blindness and deafness. Polarographic and spectrophotometric analyses in
      fibroblasts and liver revealed a respiratory chain (RC) dysfunction.
      Surprisingly, we identified a homozygous nonsense mutation in the GM3 synthase
      gene by using exome sequencing. GM3 synthase catalyzes the formation of GM3
      ganglioside from lactosylceramide, which is the first step in the synthesis of
      complex ganglioside species. Mass spectrometry analysis revealed that the
      complete absence of GM3 ganglioside and its biosynthetic derivatives was
      associated with an upregulation of the alternative globoside pathway in
      fibroblasts. The accumulation of Gb3 and Gb4 globosides likely has a role in RC
      dysfunction and in the decrease of mitochondrial membrane potential leading to
      apoptosis, which we observed in fibroblasts. We show for the first time that GM3
      synthase deficiency, responsible for early-onset epilepsy syndrome, leads to a
      secondary RC dysfunction. Our study highlights the role of secondary
      mitochondrial disorders that can interfere with the diagnosis and the evolution
      of other metabolic diseases.

PMID- 22990146
TI  - Why is it difficult to publish in high-impact journals?

PMID- 22990145
TI  - EMQN/CMGS best practice guidelines for the molecular genetic testing of
      Huntington disease.
AB  - Huntington disease (HD) is caused by the expansion of an unstable polymorphic
      trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an
      extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves
      estimation of the number of CAG repeats. Molecular genetic testing for HD is
      offered in a wide range of laboratories both within and outside the European
      community. In order to measure the quality and raise the standard of molecular
      genetic testing in these laboratories, the European Molecular Genetics Quality
      Network has organized a yearly external quality assessment (EQA) scheme for
      molecular genetic testing of HD for over 10 years. EQA compares a laboratory's
      output with a fixed standard both for genotyping and reporting of the results to
      the referring physicians. In general, the standard of genotyping is very high but
      the clarity of interpretation and reporting of the test result varies more
      widely. This emphasizes the need for best practice guidelines for this disorder.
      We have therefore developed these best practice guidelines for genetic testing
      for HD to assist in testing and reporting of results. The analytical methods and
      the potential pitfalls of molecular genetic testing are highlighted and the
      implications of the different test outcomes for the consultand and his or her
      family members are discussed.

PMID- 22990147
TI  - Clinical pathway intervention compliance and effectiveness when used in the
      treatment of patients with severe sepsis and septic shock at an Intensive Care
      Unit in Spain.
AB  - The purpose of this quasi-experimental study was to assess levels of compliance
      with the intervention bundles contained in a clinical pathway used in the
      treatment of patients with severe sepsis and septic shock, and to analyze the
      pathway's impact on survival and duration of hospital stays. We used data on 125
      patients in an Intensive Care Unit, divided into a control group (N=84) and an
      intervention group (N=41). Levels of compliance increased from 13.1% to 29.3% in
      5 resuscitation bundle interventions and from 14.3% to 22% in 3 monitoring bundle
      interventions. In-hospital mortality at 28 days decreased by 11.2% and the
      duration of hospital stay was reduced by 5 days. Although compliance was low, the
      intervention enhanced adherence to the instructions given in the clinical pathway
      and we observed a decline in mortality at 28 days and shorter hospital stays.

PMID- 22990148
TI  - Sleeping difficulties reported by patients with heart failure.
AB  - The study aimed to describe the reports of heart failure patients on the factors
      that cause difficulties to sleep and the association of these factors with the
      quality of sleep. This cross-sectional study involved a non-probabilistic sample
      of 400 patients (mean age 57.8 years, 64.8% were men, average education of 6.1
      years, 82.5% in functional class II or III) with heart failure. The main factors
      associated with sleeping difficulty were: nocturia, interrupted sleep at night
      and breathing difficulty. Sleeping difficulties in heart failure patients are
      diverse and there is an association between these difficulties and quality of
      sleep. Most of these disorders warrant professional nursing interventions.

PMID- 22990149
TI  - Nursing care time and quality indicators for adult intensive care: correlation
      analysis.
AB  - The objective of this quantitative, correlational and descriptive study was to
      analyze the time the nursing staff spends to assist patients in Adult Intensive
      Care Units, as well as to verify its correlation with quality care indicators.
      The average length of time spent on care and the quality care indicators were
      identified by consulting management instruments the nursing head of the Unit
      employs. The average hours of nursing care delivered to patients remained stable,
      but lower than official Brazilian agencies' indications. The correlation between
      time of nursing care and the incidence of accidental extubation indicator
      indicated that it decreases with increasing nursing care delivered by nurses. The
      results of this investigation showed the influence of nursing care time, provided
      by nurses, in the outcome of care delivery.

PMID- 22990150
TI  - Evaluation of the identification protocol for newborns in a private hospital.
AB  - This exploratory-descriptive quantitative study aimed to evaluate the protocol
      for identifying newborns admitted to the Neonatal Intensive and Semi-intensive
      Therapy Unit of a private hospital. The case series was made up of 540
      observation opportunities, selected by simple random probability sampling. The
      data was collected between May and August 2010 according to a form and analyzed
      by descriptive statistic. The protocol's general performance had a conformity
      index of 82.2%. There were three stages to the protocol: identification
      components, the identification wristbands' condition and the number of
      identification wristbands. The highest percentage of conformity (93%) was
      attributed to the second stage and the lowest (89.3%) to the third, presenting a
      statistically significant difference of p= 0.046. In the group of 'special'
      neonates, 88.5% conformity was achieved. These results will make it possible to
      restructure the protocol for identifying newborns and to establish care and
      managerial goals so as to improve the quality of care and the patients' safety.

PMID- 22990151
TI  - Evaluation of an educational handbook as a knowledge-acquisition strategy for
      mastectomized women.
AB  - This descriptive, cross-sectional and quantitative study presents an analysis of
      knowledge acquired by mastectomized women concerning breast cancer after reading
      an educational handbook. The sample was composed of 125 women. Data were
      collected in a specialized cancer facility in three phases: preparatory,
      operational I and operational II. As to the knowledge acquired, the posttest
      showed an 11% increase in the number of correct answers compared to the pretest.
      The most frequent correct answer regarded a question asking the name of the
      surgery (97.60%) while the question concerning breast reconstruction obtained the
      lowest number of correct answers (58.40%). Answers to all the questions
      significantly improved in the posttest, with the exception of a question
      addressing breast reconstruction (p=0.754). The assessment of knowledge showed
      positive results after reading, suggesting that cognition is essential to
      understanding and adhering to guidance, thus the handbook is a favorable resource
      to be used in the rehabilitation of mastectomized women.

PMID- 22990152
TI  - The relationship between social support and functional capacity in elderly
      persons with cognitive alterations.
AB  - The objective of this study was to identify the relationship between social
      support and the functional capacity of elderly persons with cognitive
      alterations. It is a descriptive, cross-sectional and quantitative study. The
      subjects were 101 elderly persons registered in Family Health Centers whose
      performance in the Mini-Exam for Mental Status was below a certain specified
      level in a previous study. The Medical Outcomes Study questionnaire, Katz Index
      and Pfeffer Questionnaire were applied. The dimensions of material, affective,
      emotional, informational and positive social interaction support resulted in an
      average final score of 74.32 points, indicating a better level of material and
      affective support in relation to the other dimensions of support. There was a
      statistically significant correlation between emotional support and the Katz
      Index. Knowledge about this relationship favors the development of a nursing care
      pathway for the elderly which is capable of maintaining their functional capacity
      and ensuring satisfactory social relations.

PMID- 22990154
TI  - Imaginative construction of care: the nursing professional experience in a remote
      care service.
AB  - The direction of care delivery goes from the action to the being; a process built
      from professional experience, which gains special characteristics when the
      service is delivered by telephone. The goal of this research was to understand
      the interaction between professionals and users in a remote care service; to do
      so, a research is presented, using Grounded Theory and Symbolic Interactionism as
      theoretical references. Data were collected through eight interviews with
      professionals who deliver care by telephone. The theoretical understanding
      permitted the creation of the theoretical model of the Imaginative Construction
      of Care, which shows the interaction processes the professional experiences when
      delivering care by telephone. In this model, individual and social facts are
      added, showing the link between the concepts, with special emphasis on
      uncertainty, sensitivity and professional responsibility, as essential components
      of this experience.

PMID- 22990153
TI  - Therapeutic communication between health workers and patients concerning diabetes
      mellitus care.
AB  - The objective of this cross-sectional study was to analyze therapeutic
      communication techniques used by health workers with patients under care for
      diabetes mellitus. Data were collected in 2010 in a public facility in the
      interior of Ceara, Brazil using video camera equipment and direct observation.
      Results showed that the most frequently used techniques within the "expression"
      group were: asking questions, voicing interest, and using descriptive phrases.
      The most frequently used technique within the "clarification" group was: asking
      the patient to specify the agent of action. Finally, in regard to the
      "validation" group, only the technique "summarizing content of the interaction"
      was employed. The conclusion is that despite the use of communication techniques
      on the part of professionals, there is still an alarming gap concerning
      communication skills. Such skills should be allied with technical expertise to
      enable the delivery of qualified care to individuals with diabetes mellitus.

PMID- 22990155
TI  - Evaluation of well-being at work among nursing professionals at a University
      Hospital.
AB  - Well-being at work is based on Positive Psychology, and is defined as a
      psychological state with positive affective links towards work and also towards
      the organisation. The purpose of this study was to look at the degree of well
      being at work among nursing professionals who work at a University hospital and
      also identify differences between occupational categories and types of work
      contracts. The sample was made up of 340 professionals who answered valid scales
      of the following constructs: Work Satisfaction, Involvement with Work and
      Affective Organisational Commitment. For the analysis of the data we used SPSS,
      version 12, for descriptive statistics, and also for testing differences between
      means. The results showed an average level of well-being in the workplace and
      also differences between professional categories and work regime, when it comes
      to satisfaction with salaries and promotions, which can have a reflection in the
      quality of service provided to the patients of this University hospital.

PMID- 22990156
TI  - Production of nursing care in primary health care services.
AB  - This descriptive and quantitative study aimed to characterize the production of
      nursing care in primary health care services in a region of the city of Ribeirao
      Preto, state of Sao Paulo, Brazil. The study sample comprised care actions
      delivered by nurses and registered in the HygiaWeb Information System, from 2006
      to 2009. Statistical analysis was performed. Results showed that nursing care
      delivered by nurses accounted for 9.5 to 14.6% of total professional care
      provided by professionals. Eventual care actions were the most frequent. The
      concentration of programmatic care was higher for children, women, pregnant and
      postpartum women. In conclusion, the predominance of eventual care demonstrated
      that the health system has been focused on acute conditions. Little of nursing
      work has been directed at the achievement of comprehensiveness, considering the
      inexpressive share of longitudinal follow up in total care delivery. The
      expansion of nursing staff represents potential for care delivery to the
      population, but further qualification of nursing actions is needed.

PMID- 22990157
TI  - Factors associated with absenteeism-illness in rural workers in a timber company.
AB  - The monitoring of absenteeism-illness has revealed its high prevalence, and a
      strong relationship with work. This study aimed to analyze the factors associated
      with absenteeism-illness among the rural workers in a timber company in Minas
      Gerais, Brazil. It is an analytical cross-sectional study, carried out among 883
      workers. The medical certificates issued in the company over one year were
      surveyed. For the analysis, use was made of descriptive statistics and bi- and
      multivariable analyses. The strength of association was measured by the odds
      ratio (OR) with help from logistic regression (p<0.05). A prevalence of 54% of
      medical certificates was found in the population. Bivariate analysis revealed an
      association between job (forestry assistant (OR=13.1), carpenter (OR=15) and
      chainsaw operator (OR=39.6)), length of service in the company, departments and
      length of schooling with absenteeism-illness. In the multi-variate analysis, the
      association between length of schooling and being a carpenter disappeared, while
      the other associations remained. It is concluded that there is important evidence
      about the occupational and demographic factors and absenteeism-illness among
      forestry workers.

PMID- 22990158
TI  - Efficacy of auriculotherapy for the reduction of stress in nursing students: a
      randomized clinical trial.
AB  - This study is a randomized single-blind trial, which aimed to evaluate the
      efficacy of true auriculotherapy and placebo auriculotherapy in reducing the
      stress levels of mid-level Nursing students of the School of Nursing of the
      Beneficencia Portuguesa Hospital. Seventy-one students with average, high and
      very high scores, according to Vasconcellos' List of Stress Symptoms, were
      divided into three groups: Control (25), Auriculotherapy (24), and Placebo/Sham
      (22). They were evaluated at the baseline, 8th and 12th sessions and at the
      follow-up (15 days) and received Shen Men and Brainstem points (Auriculotherapy
      Group) and Wrist and Outer Ear points (Placebo/Sham Group). The analysis of
      variance (ANOVA) showed statistically significant differences between the
      Control/Auriculotherapy groups from the 8th session, which was maintained in the
      third and fourth evaluations (p=0.000) and between the Control/Placebo groups
      (p<0.05) at the three evaluations. It was concluded that the true auriculotherapy
      obtained better responses (45.39%) than the placebo (34.18%) in the reduction of
      the stress, but further studies are recommended for the re-evaluation of the sham
      points for stress. ClinicalTrials.gov Identifier: NCT01420848.

PMID- 22990159
TI  - Health-related quality of life and depressive symptoms in undergraduate nursing
      students.
AB  - This is a descriptive, cross-sectional study aimed at investigating the health
      related quality of life (HRQoL) of nursing students and its relationship with
      year of training, sociodemographic variables and the intensity of depressive
      symptoms. A convenience sample of 256 students, out of 353 eligible (72%),
      responded to the Medical Outcomes Study - The 36 Item Short-Form Health Survey
      (SF-36) and the Beck Depression Inventory (BDI) (self-administered). Final-year
      students, females and students with a higher intensity of depressive symptoms
      presented lower SF-36 scores in the physical functioning, vitality and social
      functioning domains. Institutional psychopedagogic support programs may minimize
      this negative impact on the HRQoL and encourage better professional performance
      of students in higher vulnerability situations.

PMID- 22990160
TI  - Nursing ethical processes in the State of Santa Catarina: characterization of
      factual elements.
AB  - OBJECTIVE: The present study aimed to characterize the processes of ethical and
      professional nursing transacted at the Regional Nursing Council of Santa Catarina
      (Coren/SC), considering their factual elements (events/offenses, causes and
      outcomes). METHOD: This descriptive, exploratory and documentary research with a
      quantitative approach was developed at Coren/SC. Data was collected from 128
      professional ethical processes in nursing, between 1999 and 2007, analyzed
      descriptively with regard to the origin of the complaints and ethical processes,
      the denouncers, the accused, the subject of the complaint and the outcome of the
      process. RESULTS: Considering the topics, out of the eight categories described,
      iatrogenesis was highlighted, as well as illegal professional practice,
      conflicting inter-professional relationships and professional responsibility of
      the nurse. CONCLUSION: The results show the need for discussion and intervention
      in concrete practical and arouse reflections about the process of professional
      training and continuous education in the institutional spaces of health, in order
      to reduce ethical occurrences in professional practice.

PMID- 22990161
TI  - Microcurrent application as analgesic treatment in venous ulcers: a pilot study.
AB  - This study aimed to evaluate the effect of microcurrent electrical stimulation on
      pain and area of venous ulcers. In a pilot study for a single-blind controlled
      clinical trial, carried out at an outpatient clinic during four weeks, 14
      subjects with venous ulcers (mean age 62+/-9 years) were divided in two groups:
      microcurrent (n=8) and control group (n=6). Pain (by Visual Analogue Scale) and
      the ulcer area were measured by planimetry. There was a significant difference
      between the two groups with respect to pain (microcurrent group from 8.5 (6.5
      9.75) to 3.5 (1-4.75) and control group from 7.5 (5.75-10) to 8.5 (5.5-10),
      p<0.01). Non-significant changes were found with respect to ulcer area
      (planimetry by graph paper, p=0.41 and by Image J, p=0.41). In conclusion, the
      application of microcurrent improves the pain of patients with venous ulcers
      (ClinicalTrials.gov: NCT01372020).

PMID- 22990162
TI  - Variables involved in the perception of psychological harassment in the nursing
      work environment.
AB  - This is a descriptive-exploratory study with a quantitative approach, with the
      objective of identifying how nurses perceive psychological harassment at work,
      the behaviors experienced and the variables involved. In collecting data, two
      questionnaires were used: one socio-professional and another for identifying the
      behaviors involving psychological harassment experienced by the subjects in the
      previous twelve months, along with the duration and frequency of the behaviors.
      At the end of the questionnaire, a dichotomous question was added, which
      addressed nurses' perceptions in relation to feeling victimized by psychological
      harassment at work. Both the questionnaires were applied in electronic and print
      format between May and September 2010. The data was analyzed through descriptive
      statistics. The results showed that some of the subjects felt that they were
      victims of psychological harassment. Only the variables related to
      characterization of the psychological harassment presented significant
      association. The following were highlighted among the most-referred-to behaviors:
      "They question your decisions" and "You receive verbal attacks criticizing work
      you have done". It's important to open spaces for discussing violence at work, so
      that managers may establish strategic measures for preventing and containing this
      type of violence, so as to ensure health, dignity and well-being at work. It is
      also important to discuss this issue in the academic space, so as to give the
      theme greater visibility, such that future nurses will be able to identify and
      appropriately confront this type of violence.

PMID- 22990163
TI  - Tuberculosis, AIDS and tuberculosis-AIDS co-infection in a large city.
AB  - This study aimed to analyze the incidence of tuberculosis (TB), AIDS and
      tuberculosis-AIDS co-infection in the municipality of Campinas, in the state of
      Sao Paulo, Brazil, in the period 2001 - 2009. A historical trend study, it uses
      secondary data from the Tuberculosis Surveillance Database of the University of
      Campinas (UNICAMP) and the Sao Paulo State STD-AIDS Center of Excellence and
      Training. It included new cases of TB, AIDS, and of tuberculosis-AIDS reported in
      the municipality of Campinas. A decrease in cases of TB until 2007 was observed,
      with an increase in 2008 and 2009. There was a general reduction in AIDS from
      2007, but with an increase among men aged 60 or over, in the years 2007 to 2009.
      For tuberculosis-AIDS co-infection, the tendency was to reduce. The proportion of
      HIV tests not undertaken, among patients with tuberculosis, was high (27.5%).
      This scenario shows the need for integration of the databanks into the planning
      and control activities.

PMID- 22990164
TI  - Representations and uses of medicinal plants in elderly men.
AB  - The aim of this study was to know and understand the representations and use of
      medicinal plants by elderly men assisted in the Family Health Strategies of
      Dourados, MS. Participated in this study, 18 elderly men aged over 60 years,
      using four or more medications. The research was conducted with qualitative
      approach. The results showed that there is still the consumption of medicinal
      plants among the elderly, especially in the treatment of minor harm. The
      representations about the plants seem anchored in the concept of safety; they are
      natural and few side effects. Its use is made concurrently with the manufactured
      medicines without regard to risk of interactions. Older men use medicinal plants,
      without however reporting to health professionals. Therefore, it is necessary
      continuing education focused on phytotherapy health team and nursing,
      contributing to safe and effective use of medicinal plants.

PMID- 22990165
TI  - Positive parenting by parents of children up to three years of age: development
      and validation of measurement scales.
AB  - This study aimed to describe the development and validation of three
      multidimensional scales in which the same 30 items, distributed among five
      dimensions, measure parents' self-perceived confidence, difficulties and
      knowledge needs in the exercise of positive parenting during the first three
      years of the child's life. The content of the scales resulted from the literature
      and exploratory studies and was validated by experts. The analysis of its
      reliability and validity, using Pearson's correlations and Cronbach's alpha, was
      based on data from a questionnaire administered to a non-probabilistic sample of
      1011 parents. In the dimensions and items, alpha-values ranged between 0.769 and
      0.890 and r-coefficients were >0.37;p <0.01. It was concluded that the scales
      measure three variables that correspond to the practice of positive parenting and
      their use permits guiding nursing support.

PMID- 22990166
TI  - Construction and content validation of the scale of predisposition to the
      occurrence of adverse events.
AB  - This study aimed to present the results of the construction and content
      validation of the Scale of Predisposition for the Occurrence of Adverse Events
      (EPEA). A descriptive research with a qualitative approach was carried out. To
      study the quality of nursing care and design the scale, we performed a literature
      review that resulted in a preliminary instrument, composed of 90 items, divided
      into two dimensions to assess the quality of health care (structure and process).
      Expert analysis and semantic analysis were applied as techniques to study the
      content validity of the instrument. The findings indicate that the operational
      version of the EPEA was composed of 64 items, grouped into two dimensions:
      structure (18 items) and process (46 items). The EPEA is the first Brazilian
      measure constructed to assess the nurses' attitudes towards the factors that may
      predispose to the occurrence of adverse events in ICU.

PMID- 22990167
TI  - Thrombotic obstruction of the central venous catheter in patients undergoing
      hematopoietic stem cell transplantation.
AB  - This is an integrative literature review with the aim of summarizing the
      prevention measures and treatment of thrombotic obstruction of long-term semi
      implanted central venous catheters, in patients undergoing hematopoietic stem
      cell transplantation. The sample consisted of seven studies, being two randomized
      controlled clinical trials, three cohort studies and two case series. Regarding
      the prevention measures, one single study demonstrated effectiveness, which was a
      cohort study on the oral use of warfarin. In relation to the treatment measures,
      three studies evidenced effectiveness, one highlighted the efficacy of
      streptokinase or urokinase, one demonstrated the benefit of using low-molecular
      weight heparin and the other treated the obstruction with heparin or urokinase.
      Catheter patency research shows a restricted evolution that does not follow the
      evolution of transplantations, mainly regarding nursing care.

PMID- 22990168
TI  - Infection control and monitoring after discharge in orthopedic surgery.

PMID- 22990169
TI  - Preventing thermolysis: precursor design for volatile copper compounds.
AB  - A copper(I) iminopyrrolidinate was synthesized and evaluated by thermal
      gravimetric analysis (TGA), solution based (1)H NMR studies and surface chemistry
      to determine its thermal stability and decomposition mechanism. Copper(I) tert
      butyl-imino-2,2-dimethylpyrrolidinate (1) demonstrated superior thermal stability
      and showed negligible decomposition in TGA experiments up to 300  degrees C as
      well as no decomposition in solutions at 165  degrees C over 3 weeks.

PMID- 22990170
TI  - Rapid magnetofluidic mixing in a uniform magnetic field.
AB  - This paper reports the investigation of mixing phenomena caused by the
      interaction between a uniform magnetic field and a magnetic fluid in a
      microfluidic chamber. The flow system consists of a water-based ferrofluid and a
      mixture of DI water and glycerol. Under a uniform magnetic field, the mismatch in
      magnetization of the fluids leads to instability at the interface and subsequent
      rapid mixing. The mismatch of magnetization is determined by concentration of
      magnetic nanoparticles. Full mixing at a relatively low magnetic flux density up
      to 10 mT can be achieved. The paper discusses the impact of key parameters such
      as magnetic flux density, flow rate ratio and viscosity ratio on the mixing
      efficiency. Two main mixing regimes are observed. In the improved diffusive
      mixing regime under low field strength, magnetic particles of the ferrofluid
      migrate into the diamagnetic fluid. In the bulk transport regime under high field
      strength, the fluid system is mixed rapidly by magnetically induced secondary
      flow in the chamber. The mixing concept potentially provides a wireless solution
      for a lab-on-a-chip system that is low-cost, robust, free of induced heat and
      independent of pH level or ion concentration.

PMID- 22990171
TI  - Lattice thermal conductivity of graphene with conventionally isotopic defects.
AB  - The thermal conductivity of doped graphene flake of finite size is investigated
      with emphasis on the influence of the mass of the substituting atoms on this
      property. It is shown that graphene doping by small concentrations of relatively
      heavy atoms results in a disproportionately large drop in lattice thermal
      conductivity.

PMID- 22990172
TI  - A physics/circuit-based switching model for carbon-based resistive memory with
      sp2/sp3 cluster conversion.
AB  - The switching mechanism in carbon-based resistive-switching random access memory
      is modelled using a percolation approach built on the low-temperature transition
      between phases sp(3) (diamond-like and high-resistive state) and sp(2) (graphite
      like and low-resistive state) for a matrix of carbon clusters in a diamond-like
      carbon film. The switching process is described using a random circuit breaker
      network with each breaker controlled by the resistance of clusters sp(2)/sp(3).
      The key feature of the proposed model is the thermal stress-induced transition
      from sp(2) to sp(3) phase and the electric field-induced transition from sp(3) to
      sp(2) phase. Compared with experiments on the switching biasing scheme, a good
      agreement between simulation and measured data validated the accuracy of the
      proposed model.

PMID- 22990173
TI  - Usefulness of plasma epigenetic changes of five major genes involved in the
      pathogenesis of colorectal cancer.
AB  - PURPOSE: The purpose of present study was to investigate the methylation status
      of the promoter region in five genes (mothers against decapentaplegic homolog 4,
      fragile histidine triad protein, death-associated protein kinase 1, adenomatous
      polyposis coli (APC), and E-cadherin), which are known to be involved in the
      pathogenesis of colorectal cancer (CRC) and its clinicopathological significance.
      METHODS: The study subjects were 60 CRC patients, 40 patients with adenomatous
      colorectal polyp and 60 healthy control individuals. We further enrolled a total
      of 16 patients (two patients with Crohn's disease, two patients with ulcerative
      colitis, one patient with serrated adenoma, and 11 patients with colorectal
      cancer). The methylation states of the five genes were determined in peripheral
      blood plasma using methylation-specific polymerase chain reaction single-strand
      conformation polymorphism analysis. RESULTS: This study showed the most sensitive
      epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC.
      E-cadherin and APC had similar specificities and amplified 84 and 86 %,
      respectively, of CRC patients compared to non-CRC patients. Additionally, APC was
      the only marker to be significantly increased (OR = 6.67, 95 % CI = 1.19-23.4, P
      = 0.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC.
      Though we have not examined the paired cancer tissues and plasma, there was
      relatively high concordant rate (60-80 %) in our limited number of colorectal
      cancer patients. CONCLUSIONS: Five genes, promoter methylation, in plasma were
      statistically significant risk factors in CRC patients. In this study, E-cad and
      APC genes may be particularly useful epigenetic biomarkers in plasma for the
      detection of CRC. Additionally, APC may able to identify early potential CRC.

PMID- 22990174
TI  - Evaluating sterile human acellular dermal matrix in immediate expander-based
      breast reconstruction:  a multicenter, prospective, cohort study.
AB  - BACKGROUND: Human acellular dermal matrices have gained increasing use in
      immediate expander-based breast reconstruction. However, some studies suggest
      that these grafts may be associated with a higher incidence of infection and
      seroma. To evaluate complication rates after matrix-based breast reconstruction,
      the authors conducted a prospective, multicenter, cohort study to evaluate a
      sterile human acellular dermal matrix in immediate expander-based breast
      reconstruction, specifically, to determine whether it offered a more favorable
      risk profile with respect to infection and seroma. A secondary purpose was to
      determine whether the sterilization process affects graft incorporation. METHODS:
      The authors performed 65 consecutive tissue expander-based breast reconstructions
      in a cohort of patients over a 1-year period using a single protocol. Sterile
      human matrix was used in all cases. The patients were evaluated for early
      complications (infection, seroma) and graft incorporation at the time of exchange
      or definitive reconstruction. Biopsies were performed in the first 20
      reconstructions to provide histologic correlation of graft incorporation.
      RESULTS: Complications occurred in three breasts (4.6 percent), including one
      case of cellulitis (1.5 percent) and two cases of partial mastectomy flap
      necrosis (3.0 percent) that required debridement. There were no seromas or
      explantations. The grafts were incorporated in all cases and verified
      histologically in the first 20 biopsies. CONCLUSIONS: Sterile human acellular
      dermal matrix can offer reliable matrix incorporation and a low complication
      rate. Sterilization does not negatively impact incorporation of the graft. The
      infection and seroma rates in this prospective study compare favorably to those
      in previous studies with nonsterilized (aseptic) acellular dermal matrix.

PMID- 22990175
TI  - Bispectral index versus minimum alveolar concentration for prevention of
      intraoperative awareness: does a practical controlled trial provide CERtainty?

PMID- 22990176
TI  - Ultrasonography in the intensive care unit: looking at the world through colored
      glasses.

PMID- 22990178
TI  - Prevention of intraoperative awareness with explicit recall in an unselected
      surgical population: a randomized comparative effectiveness trial.
AB  - BACKGROUND: Intraoperative awareness with explicit recall occurs in approximately
      0.15% of all surgical cases. Efficacy trials based on the Bispectral Index(r)
      (BIS) monitor (Covidien, Boulder, CO) and anesthetic concentrations have focused
      on high-risk patients, but there are no effectiveness data applicable to an
      unselected surgical population. METHODS: We conducted a randomized controlled
      trial of unselected surgical patients at three hospitals of a tertiary academic
      medical center. Surgical cases were randomized to alerting algorithms based on
      either BIS values or anesthetic concentrations. The primary outcome was the
      incidence of definite intraoperative awareness; prespecified secondary outcomes
      included postanesthetic recovery variables. RESULTS: The study was terminated
      because of futility. At interim analysis the incidence of definite awareness was
      0.12% (11/9,376) (95% CI: 0.07-0.21%) in the anesthetic concentration group and
      0.08% (8/9,460) (95% CI: 0.04-0.16%) in the BIS group (P = 0.48). There was no
      significant difference between the two groups in terms of meeting criteria for
      recovery room discharge or incidence of nausea and vomiting. By post hoc
      secondary analysis, the BIS protocol was associated with a 4.7-fold reduction in
      definite or possible awareness events compared with a cohort receiving no
      intervention (P = 0.001; 95% CI: 1.7-13.1). CONCLUSION: This negative trial could
      not detect a difference in the incidence of definite awareness or recovery
      variables between monitoring protocols based on either BIS values or anesthetic
      concentration. By post hoc analysis, a protocol based on BIS monitoring reduced
      the incidence of definite or possible intraoperative awareness compared with
      routine care.

PMID- 22990179
TI  - Deep impact of ultrasound in the intensive care unit: the "ICU-sound" protocol.
AB  - BACKGROUND: Ultrasound can influence the diagnosis and impact the treatment plan
      in critical patients. The aim of this study was to determine whether, without
      encountering major environment- or patient-related limitations, ultrasound
      examination under a critical care ultrasonography protocol can be performed to
      detect occult anomalies, to prompt urgent changes in therapy or induce further
      testing or interventions, and to confirm or modify diagnosis. METHODS: One
      hundred and twenty-five consecutive patients admitted to a general intensive care
      unit were assessed under a critical care ultrasonography protocol, and the data
      were analyzed prospectively. Systematic ultrasound examination of the optic
      nerve, thorax, heart, abdomen, and venous system was performed at the bedside.
      RESULTS: Environmental conditions hampered the examination slightly in 101/125
      patients (80.8%), moderately in 20/125 patients (16%), and strongly in 4/125
      patients (3.2%). Ultrasonographic findings modified the admitting diagnosis in
      32/125 patients (25.6%), confirmed it in 73/125 patients (58.4%), were not
      effective in confirming or modifying it in 17/125 patients (13.6%), and missed it
      in 3/125 patients (2.4%). Ultrasonographic findings prompted further testing in
      23/125 patients (18.4%), led to changes in medical therapy in 22/125 patients
      (17.6%), and to invasive procedures in 27/125 patients (21.6%). CONCLUSIONS: In
      this series of patients consecutively admitted to an intensive care unit,
      ultrasound examination revealed a high prevalence of unsuspected clinical
      abnormalities, with the highest number of new ultrasound abnormalities detected
      in patients with septic shock. As part of rapid global assessment of the patient
      on admission, our ultrasound protocol holds potential for improving healthcare
      quality.

PMID- 22990183
TI  - Comparative performance of direct and video laryngoscopes in patients with
      predicted difficult airway.

PMID- 22990184
TI  - At higher risk of difficulty is not true difficulty:  the challenge of device
      performance assessment in the difficult airway.

PMID- 22990188
TI  - Whole blood:  more than the sum of the parts.

PMID- 22990186
TI  - Tracheal intubation performed with GlideScope(r) video laryngoscope and direct
      laryngoscopy in neonates and infants.

PMID- 22990190
TI  - 'Evidence' for practice guidelines for central venous access?

PMID- 22990191
TI  - Removal of central venous catheters.

PMID- 22990193
TI  - Alternatives to preoperative transfusion should be preferred in anemic cardiac
      surgical patients instead of useless transfusion.

PMID- 22990195
TI  - Table your contaminated equipment during induction.

PMID- 22990197
TI  - Neurotoxicity: rats versus neonates.

PMID- 22990203
TI  - CLCA2, a target of the p53 family, negatively regulates cancer cell migration and
      invasion.
AB  - The tumor suppressor p53 transcriptionally regulates a number of genes that are
      involved in cell-cycle inhibition, apoptosis and the maintenance of genetic
      stability. Recent studies suggest that p53 also contributes to the regulation of
      cell migration and invasion. Here, we show that human chloride channel accessory
      2 (CLCA2) is a target gene of the p53 family (p53, p73 and p63). CLCA2 is induced
      by DNA damage in a p53-dependent manner. The p53 family proteins activate the
      CLCA2 promoter by binding directly to the conserved consensus p53-binding site
      present in the CLCA2 promoter. In terms of function, ectopic expression of CLCA2
      inhibited cancer cell migration. In contrast, silencing CLCA2 with siRNA
      stimulated cancer cell migration and invasion. We also found that inactivation of
      CLCA2 enhanced the expression of focal adhesion kinase (FAK), as well as its
      promoter activation. A small-molecule FAK inhibitor reduced the effect of CLCA2
      siRNA on cell migration and invasion, suggesting that CLCA2 inhibits cancer cell
      migration and invasion through suppression of the FAK signaling pathway.
      Furthermore, there was an inverse correlation between CLCA2 and FAK expression in
      251 human breast cancer tissues. These results strongly suggest that CLCA2 is
      involved in the p53 tumor suppressor network and has a significant effect on cell
      migration and invasion.

PMID- 22990204
TI  - OSU-03012 interacts with lapatinib to kill brain cancer cells.
AB  - We have further defined mechanism(s) by which the drug OSU-03012 (OSU) kills
      brain cancer cells. OSU toxicity was enhanced by the HSP90 inhibitor 17-N
      Allylamino-17-demethoxygeldanamycin (17AAG) that correlated with reduced
      expression of ERBB1 and ERBB2. Inhibition of the extrinsic apoptosis pathway
      blocked the interaction between 17AAG and OSU. OSU toxicity was enhanced by the
      inhibitor of ERBB1/2/4, lapatinib. Knock down of ERBB1/2/4 in a cell line
      specific fashion promoted OSU toxicity. Combined exposure of cells to lapatinib
      and OSU resulted in reduced AKT and ERK1/2 activity; expression of activated
      forms of AKT and to a lesser extent MEK1 protected cells from the lethal effects
      of the drug combination. Knock down of PTEN suppressed, and expression of PTEN
      enhanced, the lethal interaction between OSU and lapatinib. Downstream of PTEN,
      inhibition of mTOR recapitulated the effects of lapatinib. Knock down of CD95,
      NOXA, PUMA, BIK or AIF, suppressed lapatinib and OSU toxicity. Knock down of MCL
      1 enhanced, and overexpression of MCL-1 suppressed, drug combination lethality.
      Lapatinib and OSU interacted in vivo to suppress the growth of established
      tumors. Collectively our data argue that the inhibition of ERBB receptor function
      represents a useful way to enhance OSU lethality in brain tumor cells.

PMID- 22990205
TI  - Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and
      zoledronic acid.
AB  - Denosumab (Dmab) and zoledronic acid (ZOL) are antiresorptive agents, with
      different mechanisms of action, that are indicated for delaying the onset of
      skeletal-related events in patients with bone metastases from solid tumors.
      Clinical and preclinical data suggest that ZOL may have also anti-angiogenic
      activity; however, the effects of Dmab (a fully humanized antibody against the
      receptor activator of nuclear factor kappa B ligand) on angiogenesis are largely
      unknown. The objective of this study was to compare the potential anti-angiogenic
      activity of Dmab with that of ZOL in preclinical models. Dmab (0.31 to 160 MUM)
      had no effect on the viability of human MDA-MB-436 and CG5 breast cancer cells or
      human umbilical vein endothelial cells (HUVECs) and no effect on tubule formation
      or invasion of HUVECs. In contrast, ZOL (0.31 to 160 MUM) decreased the viability
      of breast cancer and HUVECs in a time- and concentration-dependent manner and
      also inhibited HUVEC tubule formation and invasion. In vivo, ZOL (20 MUg/mouse
      for three times a week for three consecutive weeks) inhibited angiogenesis in
      Matrigel plugs and inhibited the growth and neo-angiogenesis of CG5 xenografts in
      athymic nude mice. In contrast, Dmab (10 mg/Kg twice a week for 4 consecutive
      weeks) had no effect on Matrigel vascularization or xenograft growth in this
      model. These findings support the potential antiangiogenic and anticancer
      activity of ZOL in vitro and in vivo and further suggest that Dmab does not have
      antiangiogenic activity. Additional studies are needed to elucidate the potential
      anticancer activity of Dmab.

PMID- 22990207
TI  - The self-breaking mechanism of atomic scale Au nanocontacts.
AB  - We have investigated the self-breaking mechanism of atomic scale Au nanocontacts
      at room temperature in air. In the conductance traces, we frequently observed
      traces showing both a 1G(0) (2e(2)/h) and 3G(0) plateaux, or only a 2G(0) plateau
      in the conductance regime below 3G(0). The statistical analysis showed a negative
      correlation between the appearance of 1G(0) and 2G(0) peaks, and a positive
      correlation between 1G(0) and 3G(0) peaks. This conductance behavior suggested
      that the symmetric triple atomic rows changed into a symmetric single row, while
      the asymmetric double rows broke without changing into a symmetric single row.
      The regular self-breaking process can be explained by the breaking of the
      thermodynamically stable Au nanocontacts which were formed during the self
      breaking of the contacts.

PMID- 22990206
TI  - Neuropsychological and neuroimaging markers in early versus late-onset
      Alzheimer's disease.
AB  - BACKGROUND: Early-onset Alzheimer's disease (EOAD) has been overshadowed by the
      more common late-onset AD (LOAD). Yet, the literature indicates EOAD may have
      less hippocampal-memory presentations and more focal neocortical localization
      early in the disease. OBJECTIVE: To evaluate these proposed differences between
      these 2 forms of AD and to explore what they inform about differences in AD
      pathophysiology. METHODS: In all, 21 patients with EOAD and 24 patients with LOAD
      matched for disease progression and severity were compared on neurocognitive
      measures and resting state fluorodeoxy-glucose positron-emission tomography (FDG
      PET). RESULTS: Patients with EOAD had worse executive functions with greater
      hypometabolism in the parietal regions; whereas patients with LOAD had worse
      confrontation naming and verbal recognition memory with greater hypometabolism in
      inferior frontotemporal regions. CONCLUSIONS: In addition to highlighting
      significant differences between EOAD and LOAD, these results reveal dissociation
      between executive deficits in AD and frontal hypometabolism, suggesting early
      disturbances of the parietal-frontal network in EOAD.

PMID- 22990208
TI  - Rational design of an immunoconjugate for selective knock-down of leukemia
      specific E2A-PBX1 fusion gene expression in human Pre-B leukemia.
AB  - The t(1;19)(q23;p13) is one of the most common chromosomal translocations in
      acute lymphoblastic leukemia (ALL) and results in production of the transforming
      oncoprotein E2A-PBX1. Here we first report a novel, biomarker-guided biotherapy
      strategy for personalized treatment of t(1;19)(+) ALL. A supervised interrogation
      of the gene expression profiles of primary leukemic cells from a cohort of 207
      children with high risk B-lineage ALL identified up-regulated CD19 gene
      expression as a biomarker for t(1;19)(+) ALL. A disulfide-linked immunoconjugate
      of a 5-amino-modified 24 mer phosphorothioate anti-sense E2A-PBX1 oligonucleotide
      (AON) with a mAb specific for a CD19 receptor (alphaCD19-AON) was prepared as a
      CD19-directed and leukemia-specific biotherapeutic agent against E2A-PBX1(+) B
      lineage ALL. Treatment of E2A-PBX1(+) leukemia cells with low nanomolar
      concentrations of alphaCD19-AON resulted in selective depletion of E2A-PBX1
      transcripts and caused apoptotic destruction and abrogation of clonogenic growth.
      Subcutaneously administered alphaCD19-AON at a total dose level of 93 nmol kg(-1)
      delivered over 14 days using a micro-osmotic pump more than doubled the leukemia
      free survival time of SCID mice in a xenograft model of E2A-PBX1(+) human B
      lineage ALL (82.0 +/- 1.9 days vs. 37.0 +/- 0.1 days, P < 0.0001). Both the AON
      moiety and the targeting CD19-specific mAb moiety were required for the in vitro
      as well as in vivo anti-leukemic activity of alphaCD19-AON. The observed in vitro
      and in vivo anti-leukemic potency of the alphaCD19-AON immunoconjugate provides
      the first preclinical proof-of-principle that t(1;19)(+) high risk B-lineage ALL
      can be treated with leukemia-specific biotherapeutic agents that knock-down E2A
      PBX1 expression.

PMID- 22990209
TI  - P-value-based regulatory motif discovery using positional weight matrices.
AB  - To analyze gene regulatory networks, the sequence-dependent DNA/RNA binding
      affinities of proteins and noncoding RNAs are crucial. Often, these are deduced
      from sets of sequences enriched in factor binding sites. Two classes of
      computational approaches exist. The first describe binding motifs by sequence
      patterns and search the patterns with highest statistical significance for
      enrichment. The second class uses the more powerful position weight matrices
      (PWMs). Instead of maximizing the statistical significance of enrichment, they
      maximize a likelihood. Here we present XXmotif (eXhaustive evaluation of matriX
      motifs), the first PWM-based motif discovery method that can optimize PWMs by
      directly minimizing their P-values of enrichment. Optimization requires computing
      millions of enrichment P-values for thousands of PWMs. For a given PWM, the
      enrichment P-value is calculated efficiently from the match P-values of all
      possible motif placements in the input sequences using order statistics. The
      approach can naturally combine P-values for motif enrichment, conservation, and
      localization. On ChIP-chip/seq, miRNA knock-down, and coexpression data sets from
      yeast and metazoans, XXmotif outperformed state-of-the-art tools, both in numbers
      of correctly identified motifs and in the quality of PWMs. In segmentation
      modules of D. melanogaster, we detect the known key regulators and several new
      motifs. In human core promoters, XXmotif reports most previously described and
      eight novel motifs sharply peaked around the transcription start site, among them
      an Initiator motif similar to the fly and yeast versions. XXmotif's sensitivity,
      reliability, and usability will help to leverage the quickly accumulating wealth
      of functional genomics data.

PMID- 22990210
TI  - Pharmacokinetics and risk evaluation of DNA vaccine against Schistosoma
      japonicum.
AB  - DNA plasmid immunization is a novel approach of preventive and therapeutic
      vaccine. More than 100 DNA vaccines have been on preclinical or clinical phase
      trials, and four kinds of DNA vaccines for livestock have been approved by USDA,
      CFIA, and APVMA. Schistosomiasis is a worldwide parasitic disease, and vaccine
      immunization is supposed to be a promising approach to control the health crisis.
      On the basis of former preclinical studies, we further focused on the
      pharmacokinetics and risk evaluation of DNA vaccine in vivo. In the present
      study, enhanced green fluorescent protein (EGFP) report gene was fused with
      Schistosoma japonicum 23 kDa transmembrane protein antigen gene (Sj23) and
      constructed into DNA vaccine pVIVO2-Sj23.EGFP. After intramuscularly injecting
      100 MUg of purified DNA vaccine plasmid to immunizate BALB/c mice, we studied the
      tissue distribution of DNA plasmid and expressed Sj23.EGFP antigen, the
      persistence time of elicited antibodies, and the risk of DNA vaccine transferred
      into intestinal microorganisms. The results showed that DNA vaccine plasmid could
      be distributed into all tissues of the body after injection; however, only few
      organs including the injected muscle were detected DNA vaccine at
      postimmunization until the 100 days by PCR technology; the detection of green
      fluorescence protein displayed that DNA vaccine could be expressed in almost
      every tissue and organs; the ELISA assay indicated the immune antibody against
      Sj23 could persist over 70 days; and the DNA vaccine transferring intestinal
      flora results was negative. The results indicated that the DNA vaccine has
      systemic protection and long-lasting effectivity and is safe to intestinal flora.

PMID- 22990211
TI  - Factors governing the growth mode of carbon nanotubes on carbon-based substrates.
AB  - The formation of carbon nanotubes (CNTs) through precipitated carbons emerging
      from supersaturated metal catalysts is an established mechanism for their growth
      during the CVD process. Here, the CNT growth mode is determined by the
      interaction between the substrate and the catalyst nanoparticle, e.g., the tip
      growth mode for the weak adhesion between them and the base-growth mode for the
      strong adhesion case. With microscopic evidence, this study reports another
      factor that governs the growth mode of CNTs on carbon-based substrates. Catalyst
      nanoparticles after only sputtering and annealing processes before the chemical
      vapor deposition (CVD) process are fully or partially wrapped with some graphitic
      layers, which are formed by carbons escaping from the carbon substrate. The
      formation of the wrapping graphitic layers is initiated by catalyst atoms
      diffusing into the carbon substrate during the catalyst sputtering process. The
      diffused catalyst atoms later coalesce into the nanoparticles, during which
      carbon atoms escape from the carbon substrate, forming the graphitic layers which
      wrap around the catalyst nanoparticles for energy minimization. Then, the carbon
      atoms generated from the catalytic reactions during the CVD process interact with
      the carbons in the graphitic layers wrapped around the catalyst nanoparticles,
      bringing about clear tip-growth of CNTs on carbon-based substrates and a stable
      interface (carbon-carbon bonding) between CNTs and carbon-based substrates.

PMID- 22990213
TI  - The most "successful" method for failing to quit smoking is unassisted cessation.

PMID- 22990214
TI  - Time to first cigarette and serum cotinine levels in adolescent smokers: National
      Health and Nutrition Examination Survey, 2007-2010.
AB  - INTRODUCTION: Nicotine dependence and uptake among adolescents remains
      challenging to characterize and measure. Among adults, a shorter time to the
      first cigarette after waking up in the morning (TTFC) has become increasingly
      recognized as an indicator of nicotine dependence because of its association with
      biological measures of nicotine exposure, smoking relapse, and failed cessation
      attempts. However, the relation between TTFC and these measures has not been
      studied among adolescents. This study explored the association between TTFC and
      cotinine among adolescent smokers. METHODS: The study utilized 2007-2008 and 2009
      2010 National Health and Nutrition Examination Survey (NHANES) data from 220
      regular adolescent smokers between the ages of 12 and 19 who provided blood
      samples for cotinine evaluation. Regression modeling was conducted to determine
      whether TTFC predicts cotinine levels, a marker of nicotine uptake. RESULTS: The
      time to first cigarette was significantly correlated with several smoking
      behaviors including number of cigarettes per day, time since last cigarette, and
      having a family member who smokes at home. Mean cotinine levels were more than
      200 ng/ml in youths who smoked within 5 min after waking, compared with less than
      34 ng/ml in youths who waited for more than 1 hr. In multiple regression models,
      a shorter time to first cigarette predicted higher cotinine levels after
      controlling for number of cigarettes per day and other factors. The TTFC was a
      predictor of cotinine for both male and female smokers. CONCLUSION: The TTFC is a
      strong indicator of nicotine dependence in adolescents and could be an important
      component in screening for high-risk smoking and the development of tailored
      adolescent smoking intervention programs.

PMID- 22990215
TI  - The relationship between age of smoking initiation and current smoking: an
      analysis of school surveys in three European countries.
AB  - INTRODUCTION: It is held that younger smoking initiates are more likely to become
      regular smokers. The definitions of smoking initiation (a puff, part of a
      cigarette, a whole cigarette) are inconsistent and raise questions about the
      robustness of the view. We sought to re-examine the relationship using adolescent
      smoking data from 3 European countries. METHODS: A stratified secondary, logistic
      regression analysis of Global Youth Tobacco Survey data was conducted using a
      design-based analysis. Subgroup analyses were conducted of 13- to 15-year olds
      from Latvia (high smoking prevalence), Slovenia (moderate prevalence), and
      Montenegro (low prevalence) who had initiated smoking. The outcome was current
      smoking--smoking everyday for the past 30 days, or smoking 10 or more days in the
      past 30 days. Smoking initiation was operationalized as a single puff of a
      cigarette, and age of smoking initiation was a derived continuous measure.
      RESULTS: In Latvia, there was a significant association between age of smoking
      initiation and current smoking for males (p < .05) and females (p < .001) when
      smoking was operationalized as smoking every day. It was only significant in
      female adolescents (p < .001) for smoking 10 or more days. In Slovenia and
      Montenegro, there was no significant relationship between age of smoking
      initiation and current smoking for either males or females. CONCLUSIONS: The
      evidence about the relationship between age of smoking initiation and current
      smoking is not clear. Explanations for the findings may relate to a lack of
      power, the specificity of the measure, or problems with the theory.

PMID- 22990212
TI  - Nicotinic regulation of energy homeostasis.
AB  - INTRODUCTION: The ability of nicotine, the primary psychoactive substance in
      tobacco smoke, to regulate appetite and body weight is one of the factors cited
      by smokers that prevents them from quitting and is the primary reason for smoking
      initiation in teenage girls. The regulation of feeding and metabolism by nicotine
      is complex, and recent studies have begun to identify nicotinic acetylcholine
      receptor (nAChR) subtypes and circuits or cell types involved in this regulation.
      DISCUSSION: We will briefly describe the primary anatomical and functional
      features of the input, output, and central integration structures of the
      neuroendocrine systems that regulate energy homeostasis. Then, we will describe
      the nAChR subtypes expressed in these structures in mammals to identify the
      possible molecular targets for nicotine. Finally, we will review the effects of
      nicotine and its withdrawal on feeding and energy metabolism and attribute them
      to potential central and peripheral cellular targets.

PMID- 22990217
TI  - Assigning dose of nicotine gum by time to first cigarette.
AB  - INTRODUCTION: Nicotine gum, a proven effective aid to cessation, comes in two
      doses: 2-mg and 4-mg. Assignment to the higher dose has traditionally been based
      on daily cigarette consumption. This paper evaluates efficacy of the gum when the
      4-mg dose is assigned based on time to first cigarette (TTFC) being <= 30 min.
      METHODS: In a secondary analysis of a randomized, double-blind, placebo
      controlled trial that allocated smokers randomly to placebo, 2-mg, or 4-mg gum
      (Garvey, A. J., Kinnunen, T., Nordstrom, B. L., Utman, C. H., Doherty, K.,
      Rosner, B., et al. (2000). Effects of nicotine gum dose by level of nicotine
      dependence. Nicotine & Tobacco Research, 2, 53-63.
      doi:10.1080/14622200050011303), we evaluated outcomes when 4-mg gum was given to
      subjects with TTFC <= 30 (n = 158, placebo n = 159). RESULTS: Active treatment
      doubled or tripled abstinence rates versus placebo. This also held among smokers
      with a history of treatment failure. The effect of 4-mg gum was significant among
      light smokers (<25 CPD) with TTFC <= 30; 2-mg gum was not. CONCLUSION: This
      analysis suggests that assigning dose of nicotine gum based on TTFC is an
      effective and appropriate means of dose allocation.

PMID- 22990216
TI  - Impact of smoking exposure change on infant birth weight among a cohort of women
      in a prenatal smoking cessation study.
AB  - INTRODUCTION: Despite the known harmful effects of smoking during pregnancy, the
      highly addicted find it difficult to quit. Decreased smoking may be regarded as a
      means of harm reduction. There is limited information on the benefits of smoking
      reduction short of quitting. This study used salivary cotinine to assess the
      impact of change in smoking exposure on birth weight in full-term infants.
      METHODS: In a prenatal smoking cessation study, smoking status was validated by
      saliva cotinine at baseline and end of pregnancy (EOP). Salivary cotinine >=15
      ng/ml defined active smoking. Based on salivary cotinine, women were grouped as
      nonsmoking/quit, light exposure (<150 ng/ml), and heavy exposure (>=150 ng/ml) at
      baseline and EOP. EOP and baseline smoking status were stratified to form smoking
      exposure change groups. Mean birth weight was compared among those who quit,
      reduced, maintained, and increased. RESULTS: Smoking cessation was associated
      with a 299 g increase in birth weight compared with sustained heavy smoking, p =
      .021. Reduced exposure from heavy to light was associated with a 199 g increase
      in birth weight compared with sustained heavy exposure, a 103 g increase compared
      with increased exposure, and a 63 g increase compared with sustained light
      exposure. Differences among continuing smokers were not statistically
      significant. CONCLUSIONS: Although not statistically significant, the increase in
      infant birth weight associated with reduction from heavy to light exposure
      suggests potential for benefit. The only statistically significant comparison was
      between quitters and sustained heavy smokers, confirming that smoking cessation
      should remain the goal for pregnant women.

PMID- 22990218
TI  - Secondhand smoke exposure among Canadians: cotinine and self-report measures from
      the Canadian Health Measures Survey 2007-2009.
AB  - INTRODUCTION: Secondhand smoke (SHS) exposure is associated with numerous adverse
      health effects, including cancer, cardiovascular disease, asthma, respiratory
      infections, and decreased pulmonary function. This study provides population
      estimates of SHS exposure among the Canadian nonsmoking population based on self
      report and urinary cotinine concentrations. METHODS: The 2007-2009 Canadian
      Health Measures Survey, a nationally representative cross-sectional survey,
      collected data from Canadians aged 6-79 years, and it includes self-report and
      urinary cotinine measures of tobacco smoke exposure (n = 4,455). RESULTS: An
      estimated 22% of nonsmokers reported being exposed to SHS every day or almost
      every day. Of those, 70% of children (6-11 years) and 48% of adolescents (12-19
      years) had detectable cotinine levels compared with 23% of adults (20-79 years).
      An estimated 77% of nonsmokers exposed to SHS only in the home had detectable
      cotinine levels compared with 11% of nonsmokers exposed to SHS only outside the
      home. Of those exposed to SHS only in the home, a higher percentage of children
      (5.1%) had detectable cotinine levels compared with adults (3.1%). CONCLUSIONS:
      Despite well-known health risks associated with exposure to tobacco smoke, a
      substantial proportion of the Canadian population continues to be exposed to SHS.
      Higher percentages of certain subpopulations had detectable cotinine
      concentrations, including children, adolescents, and those exposed to SHS in the
      home.

PMID- 22990219
TI  - Optimal carbon monoxide criteria to confirm 24-hr smoking abstinence.
AB  - INTRODUCTION: Smoking cessation is typically verified biochemically by expired
      air carbon monoxide (CO) levels below 9 ppm (i.e., <=8 ppm), but this CO
      criterion may lead many who have smoked within 24hr to be misclassified as
      abstinent. METHODS: Adult dependent smokers (N = 261; 124 men, 137 women)
      prospectively recorded each cigarette smoked and provided CO on five consecutive
      days during each of two short-term attempts to quit smoking. Participants were
      those recruited for crossover tests of the effects of placebo versus medication
      (nicotine patch or varenicline) on the ability to initiate 24-hr abstinence. All
      had either a high or low interest in permanently quitting smoking soon (within 3
      months) and were randomized to the presence or absence of daily ($12) monetary
      reinforcement of abstinence. RESULTS: Total accuracy of sensitivity to detect
      smoking (83%) plus specificity to verify abstinence (87%) was optimal at a CO
      criterion for abstinence below 5 ppm (<=4 ppm), compared with below 9 ppm
      (sensitivity of 60%, specificity of 97%). Overall CO detection of sensitivity and
      specificity was higher in those with high versus low quit interest, but
      reinforcement of abstinence made no difference. CONCLUSIONS: Results indicate a
      CO criterion half that used in most clinical research may optimally validate 24
      hr cessation and reduce misclassification of smokers as "abstinent."

PMID- 22990220
TI  - Menthol cigarettes and mortality: keeping focus on the public health standard.

PMID- 22990221
TI  - Patterns of dual use of snus and cigarettes in a mature snus market.
AB  - INTRODUCTION: We examine the prevalence of dual use of snus and cigarettes among
      Norwegian men by categorizing dual use into four categories according to the
      frequency of use of each product, considering the order of uptake of both
      products, and examining reasons for additional snus use. We compare dual users
      and exclusive cigarette smokers with respect to their smoking intensity, plans
      for quitting smoking, and future smoking identity. METHODS: We used a data pool
      of six cross-sectional, national representative surveys conducted annually in the
      period 2005-2010 containing a total of 3,524 males aged 16-74. RESULTS: 6.8% of
      men had some kind of current concomitant use of snus and cigarettes--but only 1%
      reported a daily consumption of both products. The most typical pattern of dual
      use was a combination where daily use of one product was paired with occasional
      use of the other. Dual users consumed significantly fewer cigarettes per week
      (56.6; n = 226; SD, 53.82) than smokers who had either quit snus (79.6; n = 108;
      SD, 61.47) or single smokers with no history of snus use (80.2; n = 621; SD,
      55.86). Only 24% with a history of dual use reported snus to be their first
      tobacco product, but the proportion who had initiated tobacco use with snus
      increased significantly with younger age. Among dual users with daily intake of
      snus, a majority of 53.6% reported that the purpose of their snus use was to quit
      smoking. A higher proportion of dual users (74.4%; 95% CI, 68.8-80.0; n = 235)
      than exclusive smokers (61.3%; 95% CI, 57.6-65.0; n = 658) reported that they
      most definitely or probably would be totally smoke-free 5 years into the future.
      CONCLUSIONS: In the mature snus market of Norway, the magnitude of dual use of
      cigarettes and snus is relatively small. Dual users consume fewer cigarettes, and
      a higher proportion portray themselves as smoke-free in the future than do
      exclusive cigarette smokers.

PMID- 22990222
TI  - Perceptions of smoking-related risk and worry among dual-smoker couples.
AB  - INTRODUCTION: Quit rates are lower and relapse rates are higher for people in
      close relationships with a partner who smokes. Although desire to quit is often
      related to health concerns for one's self, much less is known about psychosocial
      factors associated with quitting in dual-smoker couples. This study investigated
      relations among beliefs about smoking and desire to quit from both partners'
      perspectives. METHODS: We recruited 63 couples in which both partners smoke
      daily. Participants were aged 21-67 (M = 43.0, SD = 11.3) and had been smoking
      for 4-51 years (M = 22.9, SD = 11.3). RESULTS: Individuals' desire to quit
      related to worry about partner's health (r = .29, p < .01), perceived risk of
      partner getting a disease if the partner continues to smoke (r = .39, p < .001),
      and belief that own smoking has caused partner physical harm (r = .38, p < .001).
      Within couples, partners were modestly concordant with regard to worry about harm
      of smoking for oneself (r = .30, p < .05) and partner (r = .30, p < .05),
      perceived risk of disease for oneself (r = .26, p < .05) and partner (r = .24, p
      < .05), and desire that partner quit (r = .34, p < .01). Participants had an
      extremely strong desire (78% = 7 on 1-7 scale) for their partner's help if they
      attempt to quit. CONCLUSIONS: Dual-smoker couples are at heightened health risks
      due to exposure to passive smoke and their own smoking. Partners' perceived risk
      and worry about the harms of smoking could be important leverage points for
      smoking cessation efforts. Interventions can be informed by considering both
      partners' beliefs and by helping partners develop plans for quitting and
      supporting each other.

PMID- 22990223
TI  - Lack of association of OPRM1 genotype and smoking cessation.
AB  - INTRODUCTION: Previous studies have reported an association between MU-opioid
      receptor (OPRM1) genotype and smoking cessation, with some evidence that the
      strength of this association depends on dose of nicotine replacement therapy
      (NRT). We examined whether a single-nucleotide polymorphism in the OPRM1 gene is
      associated with cessation and whether this variant moderates the effects of
      higher doses of NRT on abstinence. METHODS: Participants were recruited from the
      practices of primary care physicians in the United Kingdom. Patients smoking an
      average of at least 10 cigarettes a day, who wanted to quit and were 18 years or
      older were eligible for inclusion. A total of N = 633 participants were recruited
      into the original trial, of whom complete data for pharmacogenetic analyses were
      available on n = 598. Logistic regression was used to test for the effects of
      OPRM1 genotype and NRT dose, including the genotype * dose interaction term, on
      smoking status at 4-week, and 26-week follow-up. Analyses were adjusted for
      potential confounders. RESULTS: There was no evidence of a genotype effect at
      either follow-up, and no evidence of a genotype * dose interaction effect.
      CONCLUSIONS: OPRM1 genotype may not affect the likelihood of smoking cessation,
      and it may not influence response to high- versus low-dose NRT. OPRM1 may have at
      most only a modest role in explaining cigarette smoking and cessation.

PMID- 22990224
TI  - Association between dopamine receptor 2 TaqIA polymorphisms and smoking behavior
      with an influence of ethnicity: a systematic review and meta-analysis update.
AB  - INTRODUCTION: The relationship between dopamine receptor D2 (DRD2) gene TaqIA
      polymorphisms and smoking behavior remains controversial. The aim of this review
      was to update a previous meta-analysis on the effect of DRD2 polymorphisms on
      smoking behavior by considering the influence of ethnicity. METHODS: This review
      presents analyses stratified by ancestry, as the samples included individuals of
      different ethnicities. Pooled effect sizes were calculated using fixed- and
      random-effects models to verify heterogeneity. We investigated the association
      for the proportion of men and Caucasians by regression analysis using the effect
      sizes calculated by each meta-analysis. RESULTS: Analysis of smoking cessation
      revealed a significant effect, which suggested that ethnic differences between
      Caucasians and Asians moderate the effect of DRD2 polymorphisms. Smoking
      initiation and rate exhibited no relationship with DRD2 polymorphisms;
      furthermore, we detected heterogeneity. Although the analysis of smoking
      persistence indicated significant effects, heterogeneity was detected. The
      finding of heterogeneity for smoking persistence and rate suggests the
      possibility of gene-gene interactions arising from ethnic differences between the
      samples. We found a significant inverse relationship between the proportion of
      men and effect sizes among Caucasians for smoking persistence and rate. Gender
      differences between Caucasian samples may moderate the effect of DRD2
      polymorphisms on smoking persistence and rate. CONCLUSIONS: Our findings indicate
      that the ethnicity of the participants alters the effect of DRD2 polymorphisms on
      smoking behavior. The observed heterogeneity may be associated with participant
      gender as a moderating factor, and the association may be specific to Caucasians.

PMID- 22990225
TI  - Converging research needs across framework convention on tobacco control
      articles: making research relevant to global tobacco control practice and policy.
AB  - Much of the research used to support the ratification of the WHO Framework
      Convention on Tobacco Control (FCTC) was conducted in high-income countries or in
      highly controlled environments. Therefore, for the global tobacco control
      community to make informed decisions that will continue to effectively inform
      policy implementation, it is critical that the tobacco control community, policy
      makers, and funders have updated information on the state of the science as it
      pertains to provisions of the FCTC. Following the National Cancer Institute's
      process model used in identifying the research needs of the U.S. Food and Drug
      Administration's relatively new tobacco law, a core team of scientists from the
      Society for Research on Nicotine and Tobacco identified and commissioned
      internationally recognized scientific experts on the topics covered within the
      FCTC. These experts analyzed the relevant sections of the FCTC and identified
      critical gaps in research that is needed to inform policy and practice
      requirements of the FCTC. This paper summarizes the process and the common themes
      from the experts' recommendations about the research and related infrastructural
      needs. Research priorities in common across Articles include improving
      surveillance, fostering research communication/collaboration across organizations
      and across countries, and tracking tobacco industry activities. In addition,
      expanding research relevant to low- and middle-income countries (LMIC), was also
      identified as a priority, including identification of what existing research
      findings are transferable, what new country-specific data are needed, and the
      infrastructure needed to implement and disseminate research so as to inform
      policy in LMIC.

PMID- 22990226
TI  - Abuse potential of non-nicotine tobacco smoke components: acetaldehyde,
      nornicotine, cotinine, and anabasine.
AB  - INTRODUCTION: This review identified published animal studies evaluating the
      possible abuse potential of acetaldehyde, nornicotine, cotinine, and anabasine
      based on five commonly used paradigms. These include their effects on midbrain
      dopamine (DA) levels, drug discrimination and substitution for known drugs of
      abuse, place conditioning, self-administration behavior, and somatic withdrawal
      symptoms. RESULTS: Acetaldehyde had mixed effects on midbrain DA levels and drug
      discrimination; however, it consistently produced a conditioned place preference
      and supported self-administration. The single available study on withdrawal found
      that cessation of acetaldehyde administration resulted in a somatic withdrawal
      syndrome. Nornicotine increased DA in the midbrain, especially in the nucleus
      accumbens. Although there are no data on place conditioning, it substituted for
      nicotine in drug discrimination testing, partially substituted for cocaine and
      amphetamine, and, though only a single study, supported self-administration.
      Anabasine increased midbrain DA levels and that it partially substituted for
      nicotine in drug discrimination testing. Cotinine increased midbrain DA levels
      and substituted for nicotine. CONCLUSIONS: The existing literature suggests that
      acetaldehyde and nornicotine likely possess abuse potential, with anabasine
      having possible abuse potential. Although some cotinine data were available, it
      was insufficient to draw conclusions about possible abuse potential. Further
      research is needed to determine the role of minor alkaloids on tobacco
      dependence.

PMID- 22990227
TI  - Assessment of mouth-level exposure to tobacco constituents in U.S. snus
      consumers.
AB  - INTRODUCTION: When assessing the health risks associated with different tobacco
      product categories (e.g., combustible and noncombustible), it is important to
      understand exposure. Snus, a smokeless tobacco product with lower levels of most
      tobacco-related toxicants than cigarette smoke, has been recently introduced in
      the United States. The objective of this study was to evaluate the mouth-level
      exposure (MLE) to selected tobacco constituents from snus by adult consumers of
      Camel SNUS (CSNUS). METHODS: For 7 days, 53 adult CSNUS consumers used their
      usual brand styles ad libitum, collecting their snus pouches after use. The
      collected pouches and unused product were analyzed for nicotine, N'
      nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK),
      N'-nitrosoanabasine (NAB), N'-nitrosoanatabine (NAT), benzo[a]pyrene (B[a]P),
      arsenic, cadmium, chromium, lead, and nickel. MLE was estimated using the
      difference between the constituent amounts in the used and unused snus products.
      RESULTS: CSNUS consumption averaged 3.3 pouches/day or approximately 1.98 g/day.
      Mean nicotine MLE was 2.8 mg/pouch or 9.4 mg/day. Mean MLE to total tobacco
      specific nitrosamines (TSNAs: NNK, NNN, NAB, and NAT) was 171.5 ng/pouch or 527.7
      ng/day. B[a]P MLE averaged 0.2 ng/pouch or 0.68 ng/day. CONCLUSIONS: This study
      is the first to report snus MLE under normal conditions of use in a group of
      adult, U.S. snus consumers. On average, approximately 60%-90% of the amounts of
      nicotine, TSNAs, and B[a]P initially present in a snus pouch remained in the
      pouch after use by snus consumers in this study. The results from this study
      provide a preliminary assessment of exposure to constituents present in snus,
      which is potentially useful in risk assessment.

PMID- 22990228
TI  - The effect of graphic cigarette warning labels on smoking behavior: evidence from
      the Canadian experience.
AB  - INTRODUCTION: There is a substantial literature that graphic tobacco warnings are
      effective; however, there is limited evidence based on actual smoking behavior.
      The objective of this paper is to assess the effect of graphic cigarette warning
      labels on smoking prevalence and quit attempts. METHODS: A nationally
      representative sample of individuals aged 15 years and older from the Canadian
      National Population Health Survey 1998-2008 is used. The sample consists of 4,853
      individuals for the smoking prevalence regression and 1,549 smokers for quit
      attempts. The generalized estimating equation (GEE) model was used to examine the
      population-averaged (marginal) effects of tobacco graphic warnings on smoking
      prevalence and quit attempts. To assess the effect of graphic tobacco health
      warnings on smoking behavior, we used a scaled variable that takes the value of 0
      for the first 6 months in 2001, then increases gradually to 1 from December 2001.
      RESULTS: We found that graphic warnings had a statistically significant effect on
      smoking prevalence and quit attempts. In particular, the warnings decreased the
      odds of being a smoker (odds ratio [OR] = 0.875; 95% CI = 0.821-0.932) and
      increased the odds of making a quit attempt (OR = 1.330, CI = 1.187-1.490).
      Similar results were obtained when we allowed for more time for the warnings to
      appear in retail outlets. CONCLUSION: This study adds to the growing body of
      evidence on the effectiveness of graphic warnings. Our findings suggest that
      warnings had a significant effect on smoking prevalence and quit attempts in
      Canada.

PMID- 22990230
TI  - Ionothermal synthesis of two open-framework zirconium phosphates and their gas
      adsorption properties.
AB  - From a deep eutectic mixture consisting of trimethylammonium chloride (TMACl) and
      oxalic acid, two templated zirconium phosphates, ZrPOF-TMA1 with 8- and 10-ring
      pore channels as well as ZrPOF-TMA2 with 7- and 8-ring pore channels, have been
      synthesized. A low P/Zr ratio is necessary for ZrPOF-TMA1, and higher P/Zr ratios
      tend to form ZrPOF-TMA2, but the former cannot be obtained by templating TMACl
      under hydrothermal conditions. This is the first example in which a
      trimethylammonium cation, a protonated tertiary amine, has been used as a
      template to successfully synthesize two microporous zirconium phosphate
      materials, showing the potential for novel chemistry in ionothermal reactions.
      Both materials have a relatively high thermal stability and are stable up to 410 
      degrees C. Of the two microporous materials, ZrPOF-TMA2 with small pore openings
      exhibits a highly effective pore-selective behaviour that can discriminate
      between CO(2) and CH(4), with a CO(2)/CH(4) adsorption ratio of 12.7 at 1 bar.

PMID- 22990229
TI  - The relative risk to health from snus and cigarettes: response to Grimsrud et
      al.'s commentary on "perceptions of the relative harmfulness of snus among
      Norwegian general practitioners and their effect on the tendency to recommend
      snus in smoking cessation".

PMID- 22990231
TI  - Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor
      polymorphisms and serum 25(OH)D.
AB  - SETTING: All India Institute of Medical Sciences and Rajan Babu Institute of
      Pulmonary Medicine and Tuberculosis, New Delhi, India. OBJECTIVE: To investigate
      the association of vitamin D receptor (VDR) polymorphisms and serum 25(OH)D with
      susceptibility to, and response to treatment  of, multidrug-resistant
      tuberculosis (MDR-TB) in comparison with drug-susceptible pulmonary TB (DS-PTB)
      and healthy controls. DESIGN: Cross-sectional study. METHODS: A total of 897
      participants from northern India were consecutively enrolled into three groups
      (MDR-TB 354, DS-PTB 338,  controls 205). Genotypic and allelic frequencies of
      FokI, BsmI and TaqI VDR polymorphisms, and serum 25(OH)D, calcium and intact
      parathyroid hormone were measured in all participants. In those with active TB,
      disease severity, time to sputum smear and culture conversion  were correlated
      with VDR genotype and biochemical parameters. RESULTS: FokI Ff genotype and TaqI
      t allele correlated positively with MDR-TB; Ff genotype and f allele of FokI
      frequency were higher in both TB groups. BsmI Bb genotype  correlated inversely
      with MDR-TB. Serum 25(OH)D concentrations were significantly lowest in MDR-TB,
      correlating inversely with time to sputum smear conversion. CONCLUSIONS: VDR gene
      polymorphisms and hypovitaminosis D may predispose to MDR-TB. Lower serum 25(OH)D
      may increase time to MDR-TB  sputum smear negativity.

PMID- 22990232
TI  - Prasugrel versus clopidogrel: new management strategies for acute coronary
      syndrome.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is a proven treatment option
      for patients with acute coronary syndrome (ACS). Treatment of this patient
      population with antiplatelet therapy before and after percutaneous coronary
      intervention (PCI) is ever-changing. Combining clopidogrel, a thienopyridine,
      with aspirin has become the gold standard dual antiplatelet therapy. However, new
      research reveals several limitations with clopidogrel, including potential drug
      drug interactions, slow onset of action, irreversibility of platelet inhibition,
      and a wide array of patient responses. A new thienopyridine, prasugrel, has been
      approved and supported by the current guidelines for its faster onset of action,
      lack of significant drug-drug interaction, and consistent patient response.
      PURPOSE: This article will present a background of ACS and the 2 thienopyridines
      (prasugrel and clopidogrel), provide a comprehensive analysis of 4 recent trials
      comparing the 2 drugs in patients with ACS undergoing PCI, and pose 2 further
      research questions involving the genetic variability and the optimum duration of
      antiplatelet therapy after PCI. CONCLUSIONS: The American College of
      Cardiology/American Heart Association guidelines support prasugrel in patients
      specifically with ST-segment elevation myocardial infarction, non-ST-segment
      elevation myocardial infarction, previous or current stent restenosis or
      occlusion, and diabetes. Relative contraindications in patients using prasugrel
      include bleeding tendencies, age greater than 75 years, and body weight less than
      60 kg. Absolute contraindications of prasugrel use include history or current
      stroke and active bleeding. With further research looking at duration of
      treatment and cardiovascular events with prasugrel and clopidogrel, clinicians
      will be able to make more evidence-based decisions. CLINICAL IMPLICATIONS:
      Prasugrel has been shown to be an effective alternative to clopidogrel in
      treating patients with dual antiplatelet therapy for ACS requiring PCI. Awareness
      of the risks and benefits when deciding to prescribe clopidogrel or prasugrel for
      patients with ACS during and after PCI will promote patient safety, improve
      patient outcomes, and support evidence-based practice.

PMID- 22990233
TI  - Management of transradial access for coronary angiography.
AB  - The transradial approach for percutaneous coronary intervention and angiography
      has been shown to be a safe and effective alternative to the traditional
      transfemoral approach. Used extensively throughout Europe for the past 15 years,
      this technique has recently gained widespread popularity throughout the United
      States. Lower direct costs, fewer vascular complications, better patient
      acceptance, and earlier ambulation are some of the direct benefits from using
      radial access. To date, however, there has been no literature published regarding
      best practices or evidence-based guidelines for postprocedural radial access
      care. This article will discuss the advantages of transradial access in detail,
      as well as activity progression based on best practices performed at The Ohio
      State University Wexner Medical Center Richard M. Ross Heart Hospital. 

PMID- 22990234
TI  - Beat-to-beat corrected QT analysis detects corrected QT prolongation in 50
      consecutive telemetry-monitored patients.
AB  - BACKGROUND: The American Heart Association/American College of Cardiology
      Foundation recommends monitoring for corrected QT (QTc) prolongation. The
      incidence of QTc prolongation in the general public is unknown. Episodic
      measurements may miss patients at risk. OBJECTIVE: The purpose of this study was
      to determine the incidence of QTc prolongation in hospitalized telemetry patients
      when beat-to-beat monitoring, confirmed by manual calculation, was used for
      detection. METHODS: After institutional review board approval was obtained,
      waveforms of telemetry-monitored patients were analyzed consecutively until 50
      patients with prolonged QTc were identified (QTc >470 milliseconds in men and
      >480 milliseconds in women). Prolongation was confirmed by manual calculation.
      Incidence was calculated. Clinical risk factors and the outcomes of torsades de
      pointe or sudden death were explored. RESULTS: Telemetry waveforms were evaluated
      for 192 444 minutes (3207.4 hours) of recordings, yielding 8,076,653 QTc
      measurements. In 50 consecutive patients (24 [48%] men), 100% had verified
      episode(s) of QTc prolongation. Home medications that could result in QTc
      prolongation were identified in 9 patients (18%). Hospital medications with risk
      of QTc prolongation were administered to 31 patients (62%). Sixteen patients
      (32%) were not on a QTc-prolonging medication. Corrected QT prolongation risk
      factors in the history were found in 2 patients (4%) and hypomagnesemia or
      hypokalemia was seen in 6 patients (12%). Twelve-lead electrocardiogram detected
      prolonged QTc in 13 of 45 patients (26%). Prolongation of QTc was detected by
      standard of care manual analysis in 4 patients (8%). No patient experienced
      torsades de pointe or sudden death. CONCLUSION: With beat-to-beat analysis, QTc
      prolongation was detected in 100% of 50 consecutive patients where standard of
      care (nursing manual analysis or 12-lead electrocardiogram) would have detected
      28%. Hospital medications were more likely to contribute to QTc prolongation than
      home medications. IMPLICATIONS FOR PRACTICE: More specific definitions for
      determining proarrhythmic risk are needed as automated technology improves the
      capture rate of QTc prolongation events.

PMID- 22990235
TI  - Atp23 biogenesis reveals a chaperone-like folding activity of Mia40 in the IMS of
      mitochondria.
AB  - Mia40 is a recently identified oxidoreductase in the intermembrane space (IMS) of
      mitochondria that mediates protein import in an oxidation-dependent reaction.
      Substrates of Mia40 that were identified so far are of simple structure and
      receive one or two disulphide bonds. Here we identified the protease Atp23 as a
      novel substrate of Mia40. Atp23 contains ten cysteine residues which are oxidized
      during several rounds of interaction with Mia40. In contrast to other Mia40
      substrates, oxidation of Atp23 is not essential for its import; an Atp23 variant
      in which all ten cysteine residues were replaced by serine residues still
      accumulates in mitochondria in a Mia40-dependent manner. In vitro Mia40 can
      mediate the folding of wild-type Atp23 and prevents its aggregation. In these
      reactions, the hydrophobic substrate-binding pocket of Mia40 was found to be
      essential for its chaperone-like activity. Thus, Mia40 plays a much broader role
      in import and folding of polypeptides than previously expected and can serve as
      folding factor for proteins with complex disulphide patterns as well as for
      cysteine-free polypeptides.

PMID- 22990236
TI  - Hrp3 controls nucleosome positioning to suppress non-coding transcription in eu-
      and heterochromatin.
AB  - The positioning of the nucleosome by ATP-dependent remodellers provides the
      fundamental chromatin environment for the regulation of diverse cellular
      processes acting on the underlying DNA. Recently, genome-wide nucleosome mapping
      has revealed more detailed information on the chromatin-remodelling factors.
      Here, we report that the Schizosaccharomyces pombe CHD remodeller, Hrp3, is a
      global regulator that drives proper nucleosome positioning and nucleosome
      stability. The loss of Hrp3 resulted in nucleosome perturbation across the
      chromosome, and the production of antisense transcripts in the hrp3Delta cells
      emphasized the importance of nucleosome architecture for proper transcription.
      Notably, perturbation of the nucleosome in hrp3 deletion mutant was also
      associated with destabilization of the DNA-histone interaction and cell cycle
      dependent alleviation of heterochromatin silencing. Furthermore, the effect of
      Hrp3 in the pericentric region was found to be accomplished via a physical
      interaction with Swi6, and appeared to cooperate with other heterochromatin
      factors for gene silencing. Taken together, our data indicate that a well
      positioned nucleosome by Hrp3 is important for the spatial-temporal control of
      transcription-associated processes.

PMID- 22990237
TI  - Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient
      partitioning.
AB  - Obesity-related diseases such as diabetes and dyslipidemia result from metabolic
      alterations including the defective conversion, storage and utilization of
      nutrients, but the central mechanisms that regulate this process of nutrient
      partitioning remain elusive. As positive regulators of feeding behaviour, agouti
      related protein (AgRP) producing neurons are indispensible for the hypothalamic
      integration of energy balance. Here, we demonstrate a role for AgRP-neurons in
      the control of nutrient partitioning. We report that ablation of AgRP-neurons
      leads to a change in autonomic output onto liver, muscle and pancreas affecting
      the relative balance between lipids and carbohydrates metabolism. As a
      consequence, mice lacking AgRP-neurons become obese and hyperinsulinemic on
      regular chow but display reduced body weight gain and paradoxical improvement in
      glucose tolerance on high-fat diet. These results provide a direct demonstration
      of a role for AgRP-neurons in the coordination of efferent organ activity and
      nutrient partitioning, providing a mechanistic link between obesity and obesity
      related disorders.

PMID- 22990240
TI  - Kinetically driven self-assembly of a binary solute mixture with controlled phase
      separation via electro-hydrodynamic flow of corona discharge.
AB  - This feature article describes a new and facile process to fabricate a variety of
      thin films of non-volatile binary solute mixtures suitable for high performance
      organic electronic devices via electro-hydrodynamic flow of conventional corona
      discharge. Both Corona Discharge Coating (CDC) and a modified version of CDC,
      Scanning Corona Discharge Coating (SCDC), are based on utilizing directional
      electric flow, known as corona wind, of the charged uni-polar particles generated
      by corona discharge between a metallic needle and a bottom plate under a high
      electric field (5-10 kV cm(-1)). The electric flow rapidly spreads out the binary
      mixture solution on the bottom plate and subsequently forms a smooth and flat
      thin film in a large area within a few seconds. In the case of SCDC, the static
      movement of the bottom electrode on which a binary mixture solution is placed
      provides further control of thin film formation, giving rise to a film highly
      uniform over a large area. Interesting phase separation behaviors were observed
      including nanometer scale phase separation of a polymer-polymer binary mixture
      and vertical phase separation of a polymer-organic semiconductor mixture. Core
      shell type phase separation of either polymer-polymer or polymer-colloidal
      nanoparticle binary mixtures was also developed with a periodically patterned
      microstructure when the relative location of the corona wind was controlled to a
      binary solution droplet on a substrate. We also demonstrate potential
      applications of thin functional films with controlled microstructures by corona
      coating to various organic electronic devices such as electroluminescent diodes,
      field effect transistors and non-volatile polymer memories.

PMID- 22990238
TI  - Endocytic tubules regulated by Rab GTPases 5 and 11 are used for envelopment of
      herpes simplex virus.
AB  - Enveloped viruses employ diverse and complex strategies for wrapping at cellular
      membranes, many of which are poorly understood. Here, an ultrastructural study of
      herpes simplex virus 1 (HSV1)-infected cells revealed envelopment in tubular
      membranes. These tubules were labelled by the fluid phase marker horseradish
      peroxidase (HRP), and were observed to wrap capsids as early as 2 min after HRP
      addition, indicating that the envelope had recently cycled from the cell surface.
      Consistent with this, capsids did not colocalise with either the trans-Golgi
      network marker TGN46 or late endosomal markers, but showed coincidence with the
      transferrin receptor. Virus glycoproteins were retrieved from the plasma membrane
      (PM) to label wrapping capsids, a process that was dependent on both dynamin and
      Rab5. Combined depletion of Rab5 and Rab11 reduced virus yield to <1%, resulting
      in aberrant localisation of capsids. These results suggest that endocytosis from
      the PM into endocytic tubules provides the main source of membrane for HSV1, and
      reveal a new mechanism for virus exploitation of the endocytic pathway.

PMID- 22990243
TI  - The cover. Neuroendocrine and endocrine pathways of obesity.

PMID- 22990239
TI  - Metazoan Hsp70 machines use Hsp110 to power protein disaggregation.
AB  - Accumulation of aggregation-prone misfolded proteins disrupts normal cellular
      function and promotes ageing and disease. Bacteria, fungi and plants counteract
      this by solubilizing and refolding aggregated proteins via a powerful cytosolic
      ATP-dependent bichaperone system, comprising the AAA+ disaggregase Hsp100 and the
      Hsp70-Hsp40 system. Metazoa, however, lack Hsp100 disaggregases. We show that
      instead the Hsp110 member of the Hsp70 superfamily remodels the human Hsp70-Hsp40
      system to efficiently disaggregate and refold aggregates of heat and chemically
      denatured proteins in vitro and in cell extracts. This Hsp110 effect relies on
      nucleotide exchange, not on ATPase activity, implying ATP-driven chaperoning is
      not required. Knock-down of nematode Caenorhabditis elegans Hsp110, but not an
      unrelated nucleotide exchange factor, compromises dissolution of heat-induced
      protein aggregates and severely shortens lifespan after heat shock. We conclude
      that in metazoa, Hsp70-Hsp40 powered by Hsp110 nucleotide exchange represents the
      crucial disaggregation machinery that reestablishes protein homeostasis to
      counteract protein unfolding stress.

PMID- 22990246
TI  - Studies probe mechanisms that have a role in obesity-associated morbidities.

PMID- 22990247
TI  - Online programs help with weight loss.

PMID- 22990253
TI  - Dietary composition during weight-loss maintenance.

PMID- 22990254
TI  - Dietary composition during weight-loss maintenance.

PMID- 22990255
TI  - Dietary composition during weight-loss maintenance.

PMID- 22990257
TI  - Benefits and risks of aspirin use.

PMID- 22990258
TI  - Benefits and risks of aspirin use.

PMID- 22990260
TI  - Telephone vs face-to-face cognitive behavioral therapy for depression.

PMID- 22990262
TI  - Physical restraint use in nursing homes.

PMID- 22990264
TI  - The role of government in preventing excess calorie consumption: the example of
      New York City.

PMID- 22990265
TI  - The next generation of obesity research: no time to waste.

PMID- 22990266
TI  - FDA approval of obesity drugs: a difference in risk-benefit perceptions.

PMID- 22990267
TI  - Cardiovascular risk assessment in the development of new drugs for obesity.

PMID- 22990268
TI  - A piece of my mind. Food for thought.

PMID- 22990269
TI  - Exercise dose and diabetes risk in overweight and obese children: a randomized
      controlled trial.
AB  - CONTEXT: Pediatric studies have shown that aerobic exercise reduces metabolic
      risk, but dose-response information is not available. OBJECTIVES: To test the
      effect of different doses of aerobic training on insulin resistance, fatness,
      visceral fat, and fitness in overweight, sedentary children and to test
      moderation by sex and race. DESIGN, SETTING, AND PARTICIPANTS: Randomized
      controlled efficacy trial conducted from 2003 through 2007 in which 222
      overweight or obese sedentary children (mean age, 9.4 years; 42% male; 58% black)
      were recruited from 15 public schools in the Augusta, Georgia, area.
      INTERVENTION: Children were randomly assigned to low-dose (20 min/d; n = 71) or
      high-dose (40 min/d; n = 73) aerobic training (5 d/wk; mean duration, 13 [SD,
      1.6] weeks) or a control condition (usual physical activity; n = 78). MAIN
      OUTCOME MEASURES: The prespecified primary outcomes were postintervention type 2
      diabetes risk assessed by insulin area under the curve (AUC) from an oral glucose
      tolerance test, aerobic fitness (peak oxygen consumption [VO2]), percent body fat
      via dual-energy x-ray absorptiometry, and visceral fat via magnetic resonance,
      analyzed by intention to treat. RESULTS: The study had 94% retention (n = 209).
      Most children (85%) were obese. At baseline, mean body mass index was 26 (SD,
      4.4). Reductions in insulin AUC were larger in the high-dose group (adjusted mean
      difference, -3.56 [95% CI, -6.26 to -0.85] * 10(3) MUU/mL; P = .01) and the low
      dose group (adjusted mean difference, -2.96 [95% CI, -5.69 to -0.22] * 10(3)
      MUU/mL; P = .03) than the control group. Dose-response trends were also observed
      for body fat (adjusted mean difference, -1.4% [95% CI, -2.2% to -0.7%]; P < .001
      and -0.8% [95% CI, -1.6% to -0.07%]; P = .03) and visceral fat (adjusted mean
      difference, -3.9 cm3 [95% CI, -6.0 to -1.7 cm3]; P < .001 and -2.8 cm3 [95% CI, 
      4.9 to -0.6 cm3]; P = .01) in the high- and low-dose vs control groups,
      respectively. Effects in the high- and low-dose groups vs control were similar
      for fitness (adjusted mean difference in peak VO2, 2.4 [95% CI, 0.4-4.5]
      mL/kg/min; P = .02 and 2.4 [95% CI, 0.3-4.5] mL/kg/min; P = .03, respectively).
      High- vs low-dose group effects were similar for these outcomes. There was no
      moderation by sex or race. CONCLUSION: In this trial, after 13 weeks, 20 or 40
      min/d of aerobic training improved fitness and demonstrated dose-response
      benefits for insulin resistance and general and visceral adiposity in sedentary
      overweight or obese children, regardless of sex or race. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00108901.

PMID- 22990270
TI  - Association between urinary bisphenol A concentration and obesity prevalence in
      children and adolescents.
AB  - CONTEXT: Bisphenol A (BPA), a manufactured chemical, is found in canned food,
      polycarbonate-bottled liquids, and other consumer products. In adults, elevated
      urinary BPA concentrations are associated with obesity and incident coronary
      artery disease. BPA exposure is plausibly linked to childhood obesity, but
      evidence is lacking to date. OBJECTIVE: To examine associations between urinary
      BPA concentration and body mass outcomes in children. DESIGN, SETTING, AND
      PARTICIPANTS: Cross-sectional analysis of a nationally representative subsample
      of 2838 participants aged 6 through 19 years randomly selected for measurement of
      urinary BPA concentration in the 2003-2008 National Health and Nutrition
      Examination Surveys. MAIN OUTCOME MEASURES: Body mass index (BMI), converted to
      sex- and age-standardized z scores and used to classify participants as
      overweight (BMI >=85th percentile for age/sex) or obese (BMI >=95th percentile).
      RESULTS: Median urinary BPA concentration was 2.8 ng/mL (interquartile range, 1.5
      5.6). Of the participants, 1047 (34.1% [SE, 1.5%]) were overweight and 590 (17.8%
      [SE, 1.3%]) were obese. Controlling for race/ethnicity, age, caregiver education,
      poverty to income ratio, sex, serum cotinine level, caloric intake, television
      watching, and urinary creatinine level, children in the lowest urinary BPA
      quartile had a lower estimated prevalence of obesity (10.3% [95% CI, 7.5%-13.1%])
      than those in quartiles 2 (20.1% [95% CI, 14.5%-25.6%]), 3 (19.0% [95% CI, 13.7%
      24.2%]), and 4 (22.3% [95% CI, 16.6%-27.9%]). Similar patterns of association
      were found in multivariable analyses examining the association between quartiled
      urinary BPA concentration and BMI z score and in analyses that examined the
      logarithm of urinary BPA concentration and the prevalence of obesity. Obesity was
      not associated with exposure to other environmental phenols commonly used in
      other consumer products, such as sunscreens and soaps. In stratified analysis,
      significant associations between urinary BPA concentrations and obesity were
      found among whites (P < .001) but not among blacks or Hispanics. CONCLUSIONS:
      Urinary BPA concentration was significantly associated with obesity in this cross
      sectional study of children and adolescents. Explanations of the association
      cannot rule out the possibility that obese children ingest food with higher BPA
      content or have greater adipose stores of BPA.

PMID- 22990272
TI  - Health care use during 20 years following bariatric surgery.
AB  - CONTEXT: Bariatric surgery results in sustained weight loss; reduced incidence of
      diabetes, cardiovascular events, and cancer; and improved survival. The long-term
      effect on health care use is unknown. OBJECTIVE: To assess health care use over
      20 years by obese patients treated conventionally or with bariatric surgery.
      DESIGN, SETTING, AND PARTICIPANTS: The Swedish Obese Subjects study is an
      ongoing, prospective, nonrandomized, controlled intervention study conducted in
      the Swedish health care system that included 2010 adults who underwent bariatric
      surgery and 2037 contemporaneously matched controls recruited between 1987 and
      2001. Inclusion criteria were age 37 years to 60 years and body mass index of 34
      or higher in men and 38 or higher in women. Exclusion criteria were identical in
      both groups. INTERVENTIONS: Of the surgery patients, 13% underwent gastric
      bypass, 19% gastric banding, and 68% vertical-banded gastroplasty. Controls
      received conventional obesity treatment. MAIN OUTCOME MEASURES: Annual hospital
      days (follow-up years 1 to 20; data capture 1987-2009; median follow-up 15 years)
      and nonprimary care outpatient visits (years 2-20; data capture 2001-2009; median
      follow-up 9 years) were retrieved from the National Patient Register, and drug
      costs from the Prescribed Drug Register (years 7-20; data capture 2005-2011;
      median follow-up 6 years). Registry linkage was complete for more than 99% of
      patients (4044 of 4047). Mean differences were adjusted for baseline age, sex,
      smoking, diabetes status, body mass index, inclusion period, and (for the
      inpatient care analysis) hospital days the year before the index date. RESULTS:
      In the 20 years following their bariatric procedure, surgery patients used a
      total of 54 mean cumulative hospital days compared with 40 used by those in the
      control group (adjusted difference, 15; 95% CI, 2-27; P = .03). During the years
      2 through 6, surgery patients had an accumulated annual mean of 1.7 hospital days
      vs 1.2 days among control patients (adjusted difference, 0.5; 95% CI, 0.2 to 0.7;
      P < .001). From year 7 to 20, both groups had a mean annual 1.8 hospital days
      (adjusted difference, 0.0; 95% CI, -0.3 to 0.3; P = .95). Surgery patients had a
      mean annual 1.3 nonprimary care outpatient visits during the years 2 through 6 vs
      1.1 among the controls (adjusted difference, 0.3; 95% CI, 0.1 to 0.4; P = .003),
      but from year 7, the 2 groups did not differ (1.8 vs 1.9 mean annual visits;
      adjusted difference, -0.2; 95% CI, -0.4 to 0.1; P = .12). From year 7 to 20, the
      surgery group incurred a mean annual drug cost of US $930; the control patients,
      $1123 (adjusted difference, -$228; 95% CI, -$335 to -$121; P < .001).
      CONCLUSIONS: Compared with controls, surgically treated patients used more
      inpatient and nonprimary outpatient care during the first 6-year period after
      undergoing bariatric surgery but not thereafter. Drug costs from years 7 through
      20 were lower for surgery patients than for control patients. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01479452.

PMID- 22990271
TI  - Health benefits of gastric bypass surgery after 6 years.
AB  - CONTEXT: Extreme obesity is associated with health and cardiovascular disease
      risks. Although gastric bypass surgery induces rapid weight loss and ameliorates
      many of these risks in the short term, long-term outcomes are uncertain.
      OBJECTIVE: To examine the association of Roux-en-Y gastric bypass (RYGB) surgery
      with weight loss, diabetes mellitus, and other health risks 6 years after
      surgery. DESIGN, SETTING, AND PARTICIPANTS: A prospective Utah-based study
      conducted between July 2000 and June 2011 of 1156 severely obese (body mass index
      [BMI] >= 35) participants aged 18 to 72 years (82% women; mean BMI, 45.9; 95% CI,
      31.2-60.6) who sought and received RYGB surgery (n = 418), sought but did not
      have surgery (n = 417; control group 1), or who were randomly selected from a
      population-based sample not seeking weight loss surgery (n = 321; control group
      2). MAIN OUTCOME MEASURES: Weight loss, diabetes, hypertension, dyslipidemia, and
      health-related quality of life were compared between participants having RYGB
      surgery and control participants using propensity score adjustment. RESULTS: Six
      years after surgery, patients who received RYGB surgery (with 92.6% follow-up)
      lost 27.7% (95% CI, 26.6%-28.9%) of their initial body weight compared with 0.2%
      (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, -1.2% to 1.2%) in
      control group 2. Weight loss maintenance was superior in patients who received
      RYGB surgery, with 94% (95% CI, 92%-96%) and 76% (95% CI, 72%-81%) of patients
      receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after
      surgery, respectively. Diabetes remission rates 6 years after surgery were 62%
      (95% CI, 49%-75%) in the RYGB surgery group, 8% (95% CI, 0%-16%) in control group
      1, and 6% (95% CI, 0%-13%) in control group 2, with remission odds ratios (ORs)
      of 16.5 (95% CI, 4.7-57.6; P < .001) vs control group 1 and 21.5 (95% CI, 5.4
      85.6; P < .001) vs control group 2. The incidence of diabetes throughout the
      course of the study was reduced after RYGB surgery (2%; 95% CI, 0%-4%; vs 17%;
      95% CI, 10%-24%; OR, 0.11; 95% CI, 0.04-0.34 compared with control group 1 and
      15%; 95% CI, 9%-21%; OR, 0.21; 95% CI, 0.06-0.67 compared with control group 2;
      both P < .001). The numbers of participants with bariatric surgery-related
      hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for the RYGB surgery
      group and 2 control groups, respectively. CONCLUSION: Among severely obese
      patients, compared with nonsurgical control patients, the use of RYGB surgery was
      associated with higher rates of diabetes remission and lower risk of
      cardiovascular and other health outcomes over 6 years.

PMID- 22990273
TI  - Surgical vs conventional therapy for weight loss treatment of obstructive sleep
      apnea: a randomized controlled trial.
AB  - CONTEXT: Obstructive sleep apnea (OSA) is strongly related to obesity. Weight
      loss is recommended as part of the overall management plan for obese patients
      diagnosed with OSA. OBJECTIVE: To determine whether surgically induced weight
      loss is more effective than conventional weight loss therapy in the management of
      OSA. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial of 60 obese
      patients (body mass index: >35 and <55) with recently diagnosed (<6 months) OSA
      and an apnea-hypopnea index (AHI) of 20 events/hour or more. These patients had
      been prescribed continuous positive airway pressure (CPAP) therapy to manage OSA
      and were identified via accredited community sleep clinics. The trial was
      conducted between September 2006 and March 2009 by university- and teaching
      hospital-based clinical researchers in Melbourne, Australia. Patients with
      obesity hypoventilation syndrome, previous bariatric surgery, contraindications
      to bariatric surgery, or significant cardiopulmonary, neurological, vascular,
      gastrointestinal, or neoplastic disease were excluded. INTERVENTIONS: Patients
      were randomized to a conventional weight loss program that included regular
      consultations with a dietitian and physician, and the use of very low-calorie
      diets as necessary (n = 30) or to bariatric surgery (laparoscopic adjustable
      gastric banding; n = 30). MAIN OUTCOME MEASURES: The primary outcome was baseline
      to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to
      randomization. Secondary outcomes were changes in weight, CPAP adherence, and
      functional status. RESULTS: Patients lost a mean of 5.1 kg (95% CI, 0.8 to 9.3
      kg) in the conventional weight loss program compared with 27.8 kg (95% CI, 20.9
      to 34.7 kg) in the bariatric surgery group (P < .001). The AHI decreased by 14.0
      events/hour (95% CI, 3.3 to 24.6 events/hour) in the conventional weight loss
      group and by 25.5 events/hour (95% CI, 14.2 to 36.7 events/hour) in the bariatric
      surgery group. The between-group difference was -11.5 events/hour (95% CI, -28.3
      to 5.3 events/hour; P = .18). CPAP adherence did not differ between the groups.
      The bariatric surgery group had greater improvement in the Short Form 36 physical
      component summary score (mean, 9.3 [95% CI, 0.5 to 18.0]; P = .04). CONCLUSION:
      Among a group of obese patients with OSA, the use of bariatric surgery compared
      with conventional weight loss therapy did not result in a statistically greater
      reduction in AHI despite major differences in weight loss. TRIAL REGISTRATION:
      anzctr.org Identifier: 12605000161628.

PMID- 22990276
TI  - Progress in obesity research: reasons for optimism.

PMID- 22990274
TI  - Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese
      adults.
AB  - CONTEXT: The risk of type 2 diabetes mellitus is heterogeneous among obese
      individuals. Factors that discriminate prediabetes or diabetes risk within this
      population have not been well characterized. A dysfunctional adiposity phenotype,
      characterized by excess visceral fat and insulin resistance, may contribute to
      diabetes development in those with obesity. OBJECTIVE: To investigate
      associations between adiposity phenotypes and risk for incident prediabetes and
      diabetes in a multiethnic, population-based cohort of obese adults. DESIGN,
      SETTING, AND PARTICIPANTS: Among 732 obese participants (body mass index >=30)
      aged 30 to 65 years without diabetes or cardiovascular disease enrolled between
      2000 and 2002 in the Dallas Heart Study, we measured body composition by dual
      energy x-ray absorptiometry and magnetic resonance imaging (MRI); circulating
      adipokines and biomarkers of insulin resistance, dyslipidemia, and inflammation;
      and subclinical atherosclerosis and cardiac structure and function by computed
      tomography and MRI. MAIN OUTCOME MEASURES: Incidence of diabetes through a median
      7.0 years (interquartile range, 6.6-7.6) of follow-up. In a subgroup of 512
      participants with normal fasting glucose values at baseline, incidence of the
      composite of prediabetes or diabetes was determined. RESULTS: Of the 732
      participants (mean age, 43 years; 65% women; 71% nonwhite), 84 (11.5%) developed
      diabetes. In multivariable analysis, higher baseline visceral fat mass (odds
      ratio [OR] per 1 SD [1.4 kg], 2.4; 95% CI, 1.6-3.7), fructosamine level (OR per 1
      SD [1.1 MUmol/L], 2.0; 95% CI, 1.4-2.7), fasting glucose level (OR per 1 SD [1.1
      MUmol/L], 1.9; 95% CI, 1.4-2.6), family history of diabetes (OR, 2.3; 95% CI, 1.3
      4.3), systolic blood pressure (OR per 10 mm Hg, 1.3; 95% CI, 1.1-1.5), and weight
      gain over follow-up (OR per 1 kg, 1.06; 95% CI, 1.02-1.10) were independently
      associated with diabetes, with no associations observed for body mass index,
      total body fat, or abdominal subcutaneous fat. Among the 512 participants with
      normal baseline glucose values, the composite outcome of prediabetes or diabetes
      occurred in 39.1% and was independently associated with baseline measurements of
      visceral fat mass; levels of fasting glucose, insulin, and fructosamine; older
      age; nonwhite race; family history of diabetes; and weight gain over follow-up (P
      < .05 for each) but not with measurements of general adiposity. CONCLUSION:
      Excess visceral fat and insulin resistance, but not general adiposity, were
      independently associated with incident prediabetes and type 2 diabetes mellitus
      in obese adults.

PMID- 22990275
TI  - Progress in filling the gaps in bariatric surgery.

PMID- 22990277
TI  - JAMA patient page. Bariatric surgery.

PMID- 22990278
TI  - 'Bronchioloalveolar carcinoma':  is the term really dead? A critical review of a
      new classification system for pulmonary adenocarcinomas.
AB  - 'Bronchioloalveolar carcinoma' (BAC) is a designation that has been in use for
      over 50 years. Recently, the International Association for the Study of Lung
      Cancer, in association with the American Thoracic Society and the European
      Respiratory Society (IASLC/ATS/ERS) has recommended dropping the term altogether.
      It is argued that 'BAC' has no clear conceptual meaning, has been used in
      conjunction with invasive tumours of various types, and was applied to mucinous
      and non-mucinous tumours that are pathogenetically distinct. In addition to
      replacing 'BAC' with the standard pathological 'adenocarcinoma in situ', the
      IASLC/ATS/ERS panel also attempted to tackle the more substantial problem of
      standardising the terminology of lung adenocarcinomas that are not clearly
      invasive. By identifying 'minimally invasive adenocarcinomas' with <5 mm
      invasion, the IASLC/ATS/ERS has attempted to classify invasive tumours with
      little metastatic potential. Problems remaining with the new classification
      include use of the term 'lepidic predominant adenocarcinoma' (LPA), which
      replaces BAC with invasive components, and lack of clarity regarding what
      constitutes true invasion in well-differentiated lung adenocarcinomas.
      Specifically, the distinction between acinar growth pattern and in situ growth is
      not standardised. The basis for the new classification, as well as the plethora
      of previous attempts at classifying lung adenocarcinomas that are neither clearly
      invasive nor clearly in situ, are reviewed. Time will determine if the use of a 5
      mm limit is workable or if the term 'LPA' has traction.

PMID- 22990279
TI  - Immunostaining of glutamine synthetase is a sensitive and specific marker for
      diagnosing focal nodular hyperplasia in needle biopsy.
AB  - AIMS: Focal nodular hyperplasia (FNH) has characteristic histological features
      which may not be seen in needle biopsy specimens. We investigate the diagnostic
      role of glutamine synthetase (GS) in needle biopsy specimens. METHODS: Sixty-one
      hepatic tumours were categorised into 20 'definite' FNHs, 13 'probable' FNHs, and
      28 cases without specific diagnosis. Needle biopsy specimens of 92 non-tumourous
      lesions, 25 well-differentiated hepatocellular carcinomas (WDHCCs), and 4 high
      grade dysplastic nodules (HGDNs) and resection specimens of 10 macroregenerative
      nodules were also selected for immunohistochemical stain of GS for comparison.
      RESULTS: All 20 'definite' FNHs, nine 'probable' FNHs, and five cases without
      specific diagnosis expressed typical map-like staining pattern of GS. The
      demographic data of these five cases were similar to those of FNH. All cases of
      chronic hepatitis B and C, cirrhosis, macroregenerative nodule and peritumourous
      liver tissue showed normal pericentral/periseptal pattern. Fifteen of 25 WDHCCs
      and one HGDN showed diffuse pattern. Ten WDHCCs and two HGDNs showed negative
      staining. One HGDN showed mosaic pattern. CONCLUSIONS: Immunohistochemical
      staining of GS increases the diagnostic sensitivity of FNH in needle biopsy,
      especially in those without typical morphology. It also helps in differentiating
      FNH from other tumourous and non-tumourous lesions.

PMID- 22990280
TI  - Isolated intracranial myeloid sarcoma.

PMID- 22990281
TI  - Effect of dipolar interaction in molecular crystals.
AB  - In this paper we investigate the ground state and the nature of the transition
      from an orientational ordered phase at low temperature to the disordered state at
      high temperature in a molecular crystal. Our model is a Potts model which takes
      into account the exchange interaction J between nearest-neighbor molecules and a
      dipolar interaction between molecular axes in three dimensions. The dipolar
      interaction is characterized by two parameters: its amplitude D and the cutoff
      distance r(c). If the molecular axis at a lattice site has three orientations,
      say the x, y or z axes, then when D = 0, the system is equivalent to the 3-state
      Potts model: the transition to the disordered phase is known to be of first
      order. When D ? 0, the ground-state configuration is shown to be composed of two
      independent interpenetrating layered subsystems which form a sandwich whose
      periodicity depends on D and r(c). We show by extensive Monte Carlo simulation
      with a histogram method that the phase transition remains of first order at
      relatively large values of r(c).

PMID- 22990282
TI  - Integrating focal adhesion dynamics, cytoskeleton remodeling, and actin motor
      activity for predicting cell migration on 3D curved surfaces of the extracellular
      matrix.
AB  - An integrative cell migration model incorporating focal adhesion (FA) dynamics,
      cytoskeleton and nucleus remodeling and actin motor activity is developed for
      predicting cell migration behaviors on 3-dimensional curved surfaces, such as
      cylindrical lumens in the 3-D extracellular matrix (ECM). The work is motivated
      by 3-D microfluidic migration experiments suggesting that the migration speed and
      direction may vary depending on the cross sectional shape of the lumen along
      which the cell migrates. In this paper, the mechanical structure of the cell is
      modeled as double elastic membranes of cell and nucleus. The two elastic
      membranes are connected by stress fibers, which are extended from focal adhesions
      on the cell surface to the nuclear membrane. The cell deforms and gains traction
      as transmembrane integrins distributed over the outer cell membrane bind to
      ligands on the ECM, form focal adhesions, and activate stress fibers.
      Probabilities at which integrin ligand-receptor bonds are formed as well as
      ruptures are affected by the surface geometry, resulting in diverse migration
      behaviors that depend on the curvature of the surface. Monte Carlo simulations of
      the integrative model reveal that (a) the cell migration speed is dependent on
      the cross sectional area of the lumen with a maximum speed at a particular
      diameter or width, (b) as the lumen diameter increases, the cell tends to spread
      and migrate around the circumference of the lumen, while it moves in the
      longitudinal direction as the lumen diameter narrows, (c) once the cell moves in
      one direction, it tends to stay migrating in the same direction despite the
      stochastic nature of migration. The relationship between the cell migration speed
      and the lumen width agrees with microfluidic experimental data for cancer cell
      migration.

PMID- 22990283
TI  - AlCl3 mediated unexpected migration of sulfonyl groups: regioselective synthesis
      of 7-sulfonyl indoles of potential pharmacological interest.
AB  - A conceptually new and straightforward introduction of sulfonyl groups at the C-7
      position of an indole ring has been achieved via AlCl(3) mediated unexpected
      regioselective sulfonyl group migration for N-alkyl/aryl/heteroarylsulfonyl
      indoles affording potential inhibitors of Mycobacterium tuberculosis H37Rv
      chorismate mutase.

PMID- 22990284
TI  - Extracorporeal membrane oxygenation by single-vessel access in adults: 
      advantages and limitations.
AB  - Veno-venous extracorporeal membrane oxygenation (vvECMO) conventionally requires
      the cannulation of two vessels. Here we report our initial experience with the
      "Wang-Zwische" (WZ) double-lumen cannula. In a group of n = 36 patients single
      venous cannulation for vvECMO was performed. A retrospective analysis was
      executed. A comparison of flow characteristics to standard two-vessel cannulation
      was performed. Mean age of the patient population was 48 +/- 15 years (body mass
      index [BMI] 32 +/- 13 kg/m(2)). In n = 32 patients (89%) the cannula was
      implanted percutaneously under echo or fluoroscopic guidance in less than 30
      minutes. Nine patients were partially mobilized on extracorporeal membrane
      oxygenation (ECMO) support. Oxygenation (partial arterial oxygen tension
      [PaO(2)]/fraction of inspired oxygen [FiO(2)]) improved significantly in all
      patients from 66 mm Hg (interquartile range [IQR] 58-87 mm Hg) before ECMO to 117
      mm Hg (IQR 95-195 mm Hg, p = 0.001) after 24 hours. In seven patients (19%)
      nonfatal adverse events occurred, including three dislocations, two partial
      cannula thrombosis, one ventricular perforation, and one retroperitoneal
      hemorrhage. The negative pressures for drainage at a flow of 2.5 L/min were
      significantly lower in a standard (S) two-vessel approach compared with a WZ
      approach (S: -9 mm Hg; IQR -3 to -24 mm Hg, vs. WZ: -23 mm Hg; IQR -4 to -40 mm
      Hg; p = 0.04). The WZ cannula offers sufficient gas exchange in addition to
      certain advantages over standard cannulation, including facilitated cannulation
      in selected patients and improved mobilization.

PMID- 22990285
TI  - Flow characteristics of continuous-flow left ventricular assist devices in a
      novel open-loop system.
AB  - Fluid-pumping technology is a mature engineering subject area with a well
      documented knowledge base. However, the pump design optimization techniques
      accepted in industry are geared toward steady-state constant-flow conditions. In
      contrast, the implantation of a continuous-flow pump to aid the output of the
      human left ventricle subjects the device to perpetual variation. This study
      measures pressure-flow performance characteristics for both axial- and
      centrifugal continuous-flow rotary blood pumps across a wide range of pressure
      differential values under uniform conditions by means of a novel open-loop flow
      system. The axial-flow devices show lower hydraulic efficiency. All pumps yield
      best efficiency point at a head to flow coefficient ratio of approximately 1.7.
      The open-loop flow system accounts for the dynamic changes associated with human
      heart physiology and allows for more precise characterization of existing heart
      pumps and those in development.

PMID- 22990286
TI  - A novel approach to an anatomical adapted stent design for the percutaneous
      therapy of tricuspid valve diseases:  preliminary experiences from an engineering
      point of view.
AB  - Tricuspid valve regurgitation mostly occurs as result of dilation of the right
      ventricle, secondary to left heart valve diseases. Until recently, little
      attention has been given to the development of percutaneous therapeutic tools
      exclusively designed for tricuspid valve disease. A new approach to the
      interventional therapy of tricuspid regurgitation, in particular, the design of a
      conceptual new valve-bearing, self-expansible stent, is presented here. A three
      dimensional computer model of a right porcine heart was developed to gain a
      realistic anatomical geometry. The new design consists of two tubular stent
      elements, one inside the superior vena cava and the other inside the tricuspid
      valve annulus after being eventually equipped with a biological valve prosthesis,
      which are connected by struts. Anchoring to the heart structure is provided
      primarily by the vena cava stent, strengthened by the struts. The stents are
      designed to be cut from a 10 mm tube and later expanded to their designated
      diameter. Simulation software analyzing the expansion process with respect to the
      intended geometrical design is used in an iterative process. A validation of the
      anatomical geometry and function of the stent design inside a silicone model
      within in vitro tests and a random porcine heart shows an accurate anatomical
      fitting.

PMID- 22990287
TI  - Asymmetry of foot position and weight distribution channels the inter-leg
      coordination dynamics of standing.
AB  - The study of quiet standing has mainly been conducted in the foot side-by-side
      position with the assumption that the contribution of the lower limbs is
      structurally and functionally equivalent. The purpose of this study was to
      examine how the two mechanical factors of foot position and weight distribution
      interact to influence postural control and inter-leg coordination dynamics.
      Participants were required, while standing in either a side-by-side, staggered,
      or tandem right foot forward position, to intentionally produce three different
      levels of weight distribution (50/50, 30/70, and 70/30) over the two feet. Our
      results showed that the interaction effects of the two mechanical constraints
      were represented in both linear and nonlinear analyses. The center of pressure
      (COP) mean velocity was predominantly influenced by body weight distribution in
      the side-by-side stance, whereas foot position was more influential in the tandem
      stance. The nonlinear analysis showed that the least experienced postural
      condition (i.e., tandem stance with a 70/30 loading level) had the lowest number
      and total duration of COP(L)-COP(R) phase synchronization epochs in the AP
      direction that were compensated by "stable" coordination dynamics in the ML
      direction. The findings revealed that the staggered stance represents a "hybrid"
      blend of the properties of the side-by-side and tandem foot positions.
      Collectively, foot position and weight distribution interact to determine the
      stability and flexibility of inter-leg coordination dynamics in postural control.

PMID- 22990288
TI  - Dynamic transformation of vestibular signals for orientation.
AB  - The same pattern of vestibular afferent feedback may signify a loss of balance or
      a change in body orientation, depending upon the initial head posture. To resolve
      this ambiguity and generate an appropriate motor response, the CNS must transform
      vestibular information from a head-centred reference frame into relevant motor
      coordinates. But what if the reference frame is continuously moving? Here, we ask
      if this neural transformation process is continuously updated during a voluntary
      change in head posture. Galvanic vestibular stimulation (GVS) was used to induce
      a sensation of head roll motion in blindfolded subjects marching on the spot.
      When head orientation was fixed, this caused unconscious turning behaviour that
      was maximal during neck flexion, minimal with the head level and reversed
      direction with neck extension. Subjects were then asked to produce a continuous
      voluntary change in head pitch, while GVS was applied. As the neck moved from
      full flexion into extension, turn velocity was continuously modulated and even
      reversed direction, reflecting the pattern observed during the head-fixed
      condition. Hence, an identical vestibular input resulted in motor output which
      was dynamically modulated by changes in head pitch. However, response magnitude
      was significantly reduced, suggesting possible suppression of vestibular input
      during voluntary head movement. Nevertheless, these results show that the CNS
      continuously reinterprets vestibular exafference to account for ongoing voluntary
      changes in head posture. This may explain why the head can be moved freely
      without losing the sense of balance and orientation.

PMID- 22990289
TI  - Exploring small city maps.
AB  - The exploration of city maps has exploded recently due to the wide availability,
      increasing use of, and reliance on small positioning and navigational devices for
      personal use. In this study, subjects explored small, 3-mile diameter circular
      maps exemplifying five different types of street networks common in the United
      States, in order to locate a hypothetical city hall. Chosen locations indicated
      that subjects are able to identify more accessible sites. Monitoring eye position
      revealed that women explored maps faster, using more widely dispersed but more
      narrowly focused gaze clusters than men. The type of street network influenced
      the time spent by the eyes in a locale and differentially affected the size of
      gaze clusters between women and men, underscoring the complex interactions of
      gender-specific strategies with street network types.

PMID- 22990290
TI  - Chronological changes in inflammatory cytokines immunoreactivities in the mouse
      hippocampus after systemic administration of high dosage of tetanus toxin.
AB  - Tetanus toxin (TeT) is an exotoxin and has a capacity for neuronal binding and
      internalization. In the present study, we compared changes in the
      immunoreactivities and protein levels of interleukin (IL-) 2 as a pro
      inflammatory cytokine and IL-4 as an anti-inflammatory cytokine in the
      hippocampus proper (HP) and dentate gyrus (DG) after systemic treatment of 10 or
      100 ng/kg TeT into mice. In this study, we could not find any neuronal damage or
      loss in any subregions of the hippocampus after TeT treatment. In the control
      groups, strong IL-2 immunoreactivity was shown in the stratum pyramidal (SP) of
      the HP and in the granule cell layer (GCL) of the DG. At 6 h post-treatment, IL-2
      immunoreactivity was hardly detected in the SP and GCL; however, strong IL-2
      immunoreactivity was shown in the stratum oriens of the HP in both the groups.
      Thereafter, intermediate IL-2 immunoreactivity was shown in the SP and GCL. On
      the other hand, intermediate IL-4 immunoreactivity was detected in the SP and GCL
      of the control groups. At 6 h post-treatment, IL-4 immunoreactivity in the SP and
      GCL was apparently increased. Thereafter, IL-4 immunoreactivity was lower than
      that at 6 h post-treatment. In brief, IL-2 and 4 immunoreactivities were easily
      detected in SP and GCL in the controls and dramatically decreased and increased
      at 6 h post-treatment, respectively.

PMID- 22990291
TI  - Effect of percutaneous stimulation at different spinal levels on the activation
      of sensory and motor roots.
AB  - Percutaneous spinal stimulation is a promising new technique for understanding
      human spinal reflexes and for evaluating the pathophysiology of motor roots.
      Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral
      junctions, sites that overlie the lumbosacral enlargement. The present study
      sought to determine the best location for targeting sensory and motor roots
      during sitting. We used paired stimuli, 50 ms apart, to distinguish the
      contribution of the reflex and motor components which make up the root evoked
      potential. This assumed that post-stimulation attenuation, primarily through
      homosynaptic depression, would abolish the second potential if it was trans
      synaptic in origin. Conversely, successive responses would be unchanged if motor
      roots were being stimulated. Here, we show that sensory root reflexes were
      optimally elicited with percutaneous stimulation over the L1-L3 vertebrae.
      However, the optimal position varied between subjects and depended on the target
      muscle being studied. A collision test showed that the reflex recorded in pre
      tibial flexors was low in amplitude and was prone to crosstalk from neighbouring
      muscles. In contrast to the reflex response, direct motor root activation was
      optimal with stimulation over the more caudal L5-S1 vertebrae. The present
      results support the utility of paired stimulation for evaluating the
      topographical recruitment of sensory and motor roots to human leg muscles.

PMID- 22990292
TI  - Perception of passage through openings depends on the size of the body in motion.
AB  - Walkers need to modify their ongoing actions to meet the demands of everyday
      environments. Navigating through openings requires gait modifications if the size
      of the opening is too small relative to the body. Here we ask whether the spatial
      requirements for navigating horizontal and vertical openings differ, and, if so,
      whether walkers are sensitive to those requirements. To test walkers' sensitivity
      to demands for gait modification, we asked participants to judge whether they
      could walk through horizontal openings without shoulder rotation and through
      vertical openings without ducking. Afterward, participants walked through the
      openings, so that we could determine which opening sizes elicited gait
      modifications. Participants turned their shoulders with more space available than
      the space they left themselves for ducking. Larger buffers for horizontal
      openings may reflect different spatial requirements created by lateral sway of
      the body during walking compared to vertical bounce. In addition, greater
      variability of turning from trial to trial compared with ducking may lead walkers
      to adopt a more conservative buffer to avoid errors. Verbal judgments accurately
      predicted whether openings required gait modifications. For horizontal openings,
      participants' judgments were best predicted by the body's dynamic abilities, not
      static shoulder width. The differences between horizontal and vertical openings
      illustrate that walkers account for the dynamic properties of walking in addition
      to scaling decisions to body dimensions.

PMID- 22990293
TI  - Influence of anti-Nogo-A antibody treatment on the reorganization of callosal
      connectivity of the premotor cortical areas following unilateral lesion of
      primary motor cortex (M1) in adult macaque monkeys.
AB  - Following unilateral lesion of the primary motor cortex, the reorganization of
      callosal projections from the intact hemisphere to the ipsilesional premotor
      cortex (PM) was investigated in 7 adult macaque monkeys, in absence of treatment
      (control; n = 4) or treated with function blocking antibodies against the neurite
      growth inhibitory protein Nogo-A (n = 3). After functional recovery, though
      incomplete, the tracer biotinylated dextran amine (BDA) was injected in the
      ipsilesional PM. Retrogradely labelled neurons were plotted in the intact
      hemisphere and their number was normalized with respect to the volume of the core
      of BDA injection sites. (1) The callosal projections to PM in the controls
      originate mainly from homotypic PM areas and, but to a somewhat lesser extent,
      from the mesial cortex (cingulate and supplementary motor areas). (2) In the
      lesioned anti-Nogo-A antibody-treated monkeys, the normalized number of callosal
      retrogradely labelled neurons was up to several folds higher than in controls,
      especially in the homotypic PM areas. (3) Except one control with a small lesion
      and a limited, transient deficit, the anti-Nogo-A antibody-treated monkeys
      recovered to nearly baseline levels of performance (73-90 %), in contrast to
      persistent deficits in the control monkeys. These results are consistent with a
      sprouting and/or sparing of callosal axons promoted by the anti-Nogo-A antibody
      treatment after lesion of the primary motor cortex, as compared to untreated
      monkeys.

PMID- 22990294
TI  - Generalization of visuomotor adaptation depends on the spatial characteristic of
      visual workspace.
AB  - The present study aims to address a novel aspect of visuomotor adaptation and its
      generalization. It is based on the assumption that the spatial structure of the
      distal action space is crucial for generalization. In the experiments, the distal
      action spaces could manifest either a symmetric or parallel structure. The
      imposed visuomotor rotations in the adaptation and the following generalization
      were either the same or opposing each other. In the generalization phase, motor
      bias resulting from prior adaptation was observed, and it turned out to
      substantially depend on the property of the workspace. In Experiment 1 with a
      parallel workspace, preceding adaptation to the same rotation was more
      advantageous than adaptation to an opposing rotation. This observation was
      reversed in Experiment 2 with the symmetrical workspace: prior adaptation to an
      opposing rotation was more advantageous for the generalization than prior
      adaptation to the same rotation. Mechanisms possibly underlying the observed
      influence of the workspace configuration were discussed.

PMID- 22990296
TI  - Assessing the ligand properties of 1,3-dimesitylbenzimidazol-2-ylidene in
      ruthenium-catalyzed olefin metathesis.
AB  - The deprotonation of 1,3-dimesitylbenzimidazolium tetrafluoroborate with a strong
      base afforded 1,3-dimesitylbenzimidazol-2-ylidene (BMes), which was further
      reacted in situ with rhodium or ruthenium complexes to afford three new
      organometallic products. The compounds [RhCl(COD)(BMes)] (COD is 1,5
      cyclooctadiene) and cis-[RhCl(CO)2(BMes)] were used to probe the steric and
      electronic parameters of BMes. Comparison of the percentage of buried volume
      (%V(Bur)) and of the Tolman electronic parameter (TEP) of BMes with those
      determined previously for 1,3-dimesitylimidazol-2-ylidene (IMes) and 1,3
      dimesitylimidazolin-2-ylidene (SIMes) revealed that the three N-heterocyclic
      carbenes (NHCs) had very similar profiles. Nonetheless, changes in the
      hydrocarbon backbone subtly affected the stereoelectronic properties of these
      ligands. Accordingly, the corresponding [RuCl2(PCy3)(NHC)(=CHPh)] complexes
      displayed different catalytic behaviors in the ring-closing metathesis (RCM) of
      alpha,omega-dienes. In the benchmark cyclization of diethyl 2,2-diallylmalonate,
      the new [RuCl2(PCy3)(BMes)(=CHPh)] compound (1d) performed slightly better than
      the Grubbs second-generation catalyst (1a), which was in turn significantly more
      active than the related [RuCl2(PCy3)(IMes)(=CHPh)] initiator (1b). For the
      formation of a model trisubstituted cycloolefin, complex 1d ranked in-between
      catalyst precursors 1a and 1b, whereas in the RCM of tetrasubstituted
      cycloalkenes it lost its catalytic efficiency much more rapidly.

PMID- 22990295
TI  - Object-based attention guided by an invisible object.
AB  - Evidence for object-based attention typically comes from studies using displays
      with visible objects, and little is known about whether object-based attention
      can occur with invisible objects. We investigated this issue with a modified
      double-rectangle cuing paradigm, which was originally developed by Egly et al. (J
      Exp Psychol Gen 123:161-177, 1994). In this study, low-contrast rectangles were
      presented very briefly, which rendered them invisible to subjects. With the
      invisible rectangles, we found a classical object-based attentional effect as
      indexed by the same-object effect. We also found the instantaneous object effect
      object-based attention was dependent on the orientation of the rectangles
      presented with the target, providing evidence for the dynamic updating hypothesis
      (Ho and Yeh in Acta Psychol 132:31-39, 2009). These results suggest that object
      based attention can be guided by an invisible object in an automatic way, with a
      minimal influence from high-level top-down control.

PMID- 22990297
TI  - Geometry determination of complexes in a molecular liquid mixture using electron
      vibration-vibration two-dimensional infrared spectroscopy with a vibrational
      transition density cube method.
AB  - We demonstrate the use of a new vibrational transition density cube (VTDC) method
      for determining the geometry of complexes in a molecular liquid mixture from
      electron-vibration-vibration two-dimensional infrared (EVV 2DIR) spectra. The
      VTDC method was used to calculate the electrically-mediated intermolecular
      vibrational coupling and thereby the EVV 2DIR spectra. Using the 1:1 benzonitrile
      phenylacetylene (BN-PA) liquid mixture as a test case, the new method leads to a
      distance of 3.60 A between the interacting BN-PA pair, a much more accurate value
      than the distance previously obtained using a dipolar approximation for the
      electrical coupling. We also show that molecular dynamics simulations of the
      liquid mixture predict a modal geometry of complexation which agrees well with
      the geometry determined from the 2DIR data via VTDC analysis. We therefore
      conclude the combination of VTDC and EVV 2DIR data is a useful approach for the
      determination of the geometry of molecular complexes in the condensed phase.

PMID- 22990298
TI  - Electronic screening of patients for predisposition to Clostridium difficile
      infection in a community hospital.
AB  - BACKGROUND: Clostridium difficile infection (CDI) continues to cause significant
      morbidity and mortality among hospitalized patients. Early diagnosis, contact
      precautions, and prompt therapy are crucial to the control of the disease and its
      spread. This study aims to develop an electronic screening tool to help identify
      patients who are at risk of CDI. METHODS: Six variables associated with CDI
      including antibiotic usage, age, and admission from another facility were
      identified. Logistic regression was used to weigh the variables, and then a
      predictive model was devised to help identify which patients may be at risk for
      developing CDI. A retrospective review of 29,453 records of hospitalizations was
      conducted including 274 cases of C difficile toxin positive patients to retrieve
      data for the model. RESULTS: The final model resulted in an area under the curve
      of 0.929, which suggests that the electronic screening tool will be an accurate
      predictor of predisposition to the disease. Model testing suggests a positive
      relationship between the total weight or score and the probability of developing
      the disease. CONCLUSION: An electronic screening tool may be an effective tool to
      assist in the accurate and timely identification of patients who may be
      predisposed to CDI during hospitalization.

PMID- 22990299
TI  - "Think the sink:" Preliminary evaluation of a handwashing promotion campaign.
AB  - Owing to its utility in guiding the planning and evaluation of health promotion
      campaigns, the Theory of Planned Behavior was used to implement a 1-month
      campaign aimed at increasing handwashing among college students. Based on
      observations of bathroom users' handwashing behavior (n = 1,005) and an online
      survey (n = 188), overall handwashing did not increase as a result of the
      campaign; however, more students did use soap (58% vs 70%). Future campaigns
      designed to increase handwashing behavior in students may be advised to target
      messages according to gender difference-based responsiveness to handwashing
      norms.

PMID- 22990300
TI  - Dose conversion coefficients for paediatric CT examinations with automatic tube
      current modulation.
AB  - A common dose-saving technique used in modern CT devices is automatic tube
      current modulation (TCM), which was originally designed to also reduce the dose
      in paediatric CT patients. In order to be able to deduce detailed organ doses of
      paediatric models, dose conversion coefficients normalized to CTDI(vol) for an
      eight-week-old baby and seven- and eight-year-old children have been computed
      accounting for TCM. The relative difference in organ dose conversion coefficients
      with and without TCM is for many organs and examinations less than 10%, but can
      in some cases amount up to 30%, e.g., for the thyroid in the chest CT of the
      seven-year-old child. Overall, the impact of TCM on the conversion coefficients
      increases with increasing age. Besides TCM, also the effect of collimation and
      tube voltage on organ dose conversion coefficients has been investigated. It
      could be shown that the normalization to CTDI(vol) leads to conversion
      coefficients that can in most cases be considered to be independent of
      collimation and tube voltage.

PMID- 22990301
TI  - Immunogenicity of low-dose MF59-adjuvanted 2009 influenza A/H1N1 vaccine in
      dialysis patients.
AB  - BACKGROUND: In response to the pandemic 2009 A/H1N1 virus, monovalent MF59
      adjuvanted vaccines were prepared. Recently, single 3.75-MUg doses of MF59
      adjuvanted vaccines have shown good immunogenicity in young adults. However, the
      immunogenicity of these vaccines has not been evaluated in dialysis patients.
      METHODS: Dialysis patients received a single 3.75-MUg dose of MF59-adjuvanted
      vaccine by intramuscular injection. For immunogenicity assays, serum samples were
      obtained before vaccination and 28 days after vaccination. All sera were tested
      by hemagglutination inhibition assays. RESULTS: Overall, 48 hemodialysis (HD)
      patients and 34 peritoneal dialysis (PD) patients were included in immunogenicity
      analysis. In HD patients, geometric mean titers (GMTs) were significantly
      increased compared with baseline GMTs in both young (aged 18-60 years) and
      elderly (aged >= 60 years) patients (51.2 +/- 51.4 vs. 14.1 +/- 20.7 in young
      patients, P = 0.012; 37.9 +/- 73.9 vs. 6.8 +/- 8.0 in elderly patients, P =
      0.018, respectively). The rates of seroprotection and seroconversion were 27.6
      and 17.2 % in young patients and 31.6 and 26.3 % in elderly patients,
      respectively. Among PD patients, GMTs were increased only in young patients (39.8
      +/- 51.4 vs. 6.8 +/- 5.0, P = 0.001). The rates of seroprotection and
      seroconversion were 36.0 and 36.0 % in young patients and 11.1 and 0.0 % in
      elderly patients, respectively. CONCLUSION: A single 3.75-MUg dose of MF59
      adjuvanted vaccine was suboptimal to elicit protective antibody response in
      dialysis patients. Antibody responses against vaccine were compromised especially
      in elderly PD patients. Trials of different vaccination protocols such as a two
      dose schedule or a higher hemagglutinin antigen dose of MF59-adjuvanted vaccine
      are necessary for improving antibody response in dialysis patients.

PMID- 22990302
TI  - Renal phosphate handling in Gitelman syndrome--the results of a case-control
      study.
AB  - BACKGROUND: Patients with Gitelman syndrome, a hereditary salt-wasting
      tubulopathy, have loss-of-function mutations in the SLC12A3 gene coding for the
      thiazide-sensitive sodium chloride co-transporter in the distal convoluted
      tubule. Since the bulk of filtered phosphate is reabsorbed in the proximal
      tubule, renal phosphate wasting is considered exceptional in Gitelman syndrome.
      METHODS: We investigated the renal handling of inorganic phosphate in 12
      unselected Italian patients affected with Gitelman syndrome (5 females and 7
      males, aged 6.0-18 years, median age 12 years) and in 12 healthy subjects matched
      for gender and age (controls). The diagnosis of Gitelman syndrome among the
      patients had been made clinically and confirmed by molecular biology studies.
      RESULTS: The biochemical hallmarks of Gitelman syndrome, namely hypochloremia,
      hypokalemia, hypomagnesemia, increased urinary excretion of sodium, chloride,
      potassium and magnesium and reduced urinary excretion of calcium, were present in
      the 12 patients. In addition, both the plasma inorganic phosphate concentration
      (median and interquartile range: 1.28 [1.12-1.36] vs. 1.61 [1.51-1.66)] mmol/L)
      and the maximal tubular reabsorption of inorganic phosphate (1.08 [0.99-1.22] vs.
      1.41 [1.38-1.47] mmol/L) were significantly lower (P < 0.001) in Gitelman
      patients than in control subjects. Circulating levels of 25-hydroxyvitamin D,
      intact parathyroid hormone and osteocalcin were similar in patients and controls.
      CONCLUSIONS: The results of our case-control study disclose a hitherto
      unrecognized tendency towards renal phosphate wasting with mild to moderate
      hypophosphatemia in Gitelman syndrome.

PMID- 22990303
TI  - Angiogenesis and autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the
      growth of multiple cysts that in many cases result in end-stage renal disease.
      Current strategies to reduce cyst progression in ADPKD focus on modulating cell
      turnover, fluid secretion, and vasopressin signalling; but an alternative
      approach may be to target pathways providing "general support" for cyst growth,
      such as surrounding blood vessels. This could be achieved by altering the
      expression of growth factors involved in vascular network formation, such as the
      vascular endothelial growth factor (VEGF) and angiopoietin families. We highlight
      the evidence that blood vessels and vascular growth factors play a role in ADPKD
      progression. Recent experiments manipulating VEGF in ADPKD are described, and we
      discuss how alternative strategies to manipulate angiogenesis may be used in the
      future as a novel treatment for ADPKD. 

PMID- 22990305
TI  - Early diagnosis of pancreatic cancer; looking for a needle in a haystack?

PMID- 22990307
TI  - Activity and participation of children and adolescents with unilateral congenital
      below elbow deficiency: an online focus group study.
AB  - OBJECTIVE: To assess whether children/adolescents with unilateral congenital
      below elbow deficiency experience activity or participation limitations and how
      they deal with those limitations. METHODS: A qualitative study using online focus
      group interviews was held with 42 children/adolescents (in 3 age groups: 8-12, 13
      16, and 17-20 years), 17 parents and 19 health professionals. Questions were
      posted concerning activities, participation, prosthetic use, psychosocial
      functioning, and rehabilitation care. This study concerns the first two topics;
      activities and participation. RESULTS: Children/adolescents experienced only a
      few limitations, and there were no activities or participation situations that
      were impossible. The limitations experienced could be attributed mainly to
      environmental factors, e.g. people who lack knowledge of the child's capacities.
      Those factors were particularly decisive in transition phases.
      Children/adolescents and parents described numerous strategies applied to deal
      with the deficiency. Professionals described fewer strategies and emphasized the
      use of adaptive devices and prostheses more than other participants did.
      CONCLUSION: Having unilateral congenital below elbow deficiency did not interfere
      with any activity, but not all children/adolescents had the ability to perform
      all activities. The strategies described by children/adolescents in managing
      their deficiency should be integrated into healthcare by providing realistic
      education about the various creative solutions and possibilities of adaptive
      devices and prostheses, and should be combined with specific training.

PMID- 22990308
TI  - Sn-doped bismuth telluride nanowires with high conductivity.
AB  - Bismuth telluride (Bi(2)Te(3)) nanowires with sub-100 nm diameters were
      synthesized by Au-Sn co-catalyzed chemical vapor deposition. These Bi(2)Te(3)
      nanowires were single crystals with a hexagonal lattice. The Sn catalyst played a
      key role in achieving the one-dimensional nanowire structures, while the absence
      of Sn resulted in other morphologies such as nanoplates, nanooctahedrons and
      nanospheres. Raman spectra revealed that compared to the Bi(2)Te(3) bulk
      materials, the Bi(2)Te(3) nanowires displayed an A(1u) spectral peak, implying
      the breaking of symmetry. The temperature-dependent electrical measurement
      indicated that these Sn-doped Bi(2)Te(3) nanowires were metallic, with a high
      conductivity of 1.6 * 10(5) S m(-1) at 300 K.

PMID- 22990306
TI  - Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large
      European prospective cohort study.
AB  - OBJECTIVE: Examine the relationship between antibodies to 25 oral bacteria and
      pancreatic cancer risk in a prospective cohort study. DESIGN: We measured
      antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic
      cancer cases and 416 matched controls, nested within the European Prospective
      Investigation into Cancer and Nutrition study. Analyses were conducted using
      conditional logistic regression and additionally adjusted for smoking status and
      body mass index. RESULTS: Individuals with high levels of antibodies against
      Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a
      twofold higher risk of pancreatic cancer than individuals with lower levels of
      these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs <=200 ng/ml). To
      explore the association with commensal (non-pathogenic) oral bacteria, we
      performed a cluster analysis and identified two groups of individuals, based on
      their antibody profiles. A cluster with overall higher levels of antibodies had a
      45% lower risk of pancreatic cancer than a cluster with overall lower levels of
      antibodies (OR 0.55; 95% CI 0.36 to 0.83). CONCLUSIONS: Periodontal disease might
      increase the risk for pancreatic cancer. Moreover, increased levels of antibodies
      against specific commensal oral bacteria, which can inhibit growth of pathogenic
      bacteria, might reduce the risk of pancreatic cancer. Studies are needed to
      determine whether oral bacteria have direct effects on pancreatic cancer
      pathogenesis or serve as markers of the immune response.

PMID- 22990309
TI  - A Bayesian method for the joint estimation of outcrossing rate and inbreeding
      depression.
AB  - The population outcrossing rate (t) and adult inbreeding coefficient (F) are key
      parameters in mating system evolution. The magnitude of inbreeding depression as
      expressed in the field can be estimated given t and F via the method of Ritland
      (1990). For a given total sample size, the optimal design for the joint
      estimation of t and F requires sampling large numbers of families (100-400) with
      fewer offspring (1-4) per family. Unfortunately, the standard inference procedure
      (MLTR) yields significantly biased estimates for t and F when family sizes are
      small and maternal genotypes are unknown (a common occurrence when sampling
      natural populations). Here, we present a Bayesian method implemented in the
      program BORICE (Bayesian Outcrossing Rate and Inbreeding Coefficient Estimation)
      that effectively estimates t and F when family sizes are small and maternal
      genotype information is lacking. BORICE should enable wider use of the Ritland
      approach for field-based estimates of inbreeding depression. As proof of concept,
      we estimate t and F in a natural population of Mimulus guttatus. In addition, we
      describe how individual maternal inbreeding histories inferred by BORICE may
      prove useful in studies of inbreeding and its consequences.

PMID- 22990310
TI  - Recent range expansion and agricultural landscape heterogeneity have only minimal
      effect on the spatial genetic structure of the plant pathogenic fungus
      Mycosphaerella fijiensis.
AB  - Understanding how geographical and environmental features affect genetic
      variation at both the population and individual levels is crucial in biology,
      especially in the case of pathogens. However, distinguishing between these
      factors and the effects of historical range expansion on spatial genetic
      structure remains challenging. In the present study, we investigated the case of
      Mycosphaerella fijiensis-a plant pathogenic fungus that has recently colonized an
      agricultural landscape characterized by the presence of potential barriers to
      gene flow, including several commercial plantations in which disease control
      practises such as the use of fungicides are applied frequently, and low host
      density areas. We first genotyped 300 isolates sampled at a global scale on
      untreated plants in two dimensions over a 50 * 80-km area. Using two different
      clustering algorithms, no genetic structure was detected in the studied area,
      suggesting expansion of large populations and/or no influence of potential
      barriers. Second, we investigated the potential effect of disease control
      practises on M. fijiensis diversity by comparing populations sampled in
      commercial vs food-crop plantations. At this local scale, we detected
      significantly higher allelic richness inside commercial plantations compared with
      the surrounding food-crop plantation populations. Analysis of molecular variance
      indicated that 99% of the total genetic variance occurred within populations. We
      discuss the suggestion that high population size and/or high migration rate
      between populations might be responsible for the absence of any effect of disease
      control practises on genetic diversity and differentiation.

PMID- 22990312
TI  - Population structure and landscape genetics of two endangered frog species of
      genus Odorrana: different scenarios on two islands.
AB  - Isolation by distance and landscape connectivity are fundamental factors
      underlying speciation and evolution. To understand how landscapes affect gene
      flow and shape population structures, island species provide intrinsic study
      objects. We investigated the effects of landscapes on the population structure of
      the endangered frog species, Odorrana ishikawae and O. splendida, which each
      inhabit an island in southwest Japan. This was done by examining population
      structure, gene flow and demographic history of each species by analyzing 12
      microsatellite loci and exploring causal environmental factors through ecological
      niche modeling (ENM) and the cost-distance approach. Our results revealed that
      the limited gene flow and multiple-population structure in O. splendida and the
      single-population structure in O. ishikawae were maintained after divergence of
      the species through ancient vicariance between islands. We found that genetic
      distance correlated with geographic distance between populations of both species.
      Our landscape genetic analysis revealed that the connectivity of suitable
      habitats influences gene flow and leads to the formation of specific population
      structures. In particular, different degrees of topographical complexity between
      islands are the major determining factor for shaping contrasting population
      structures of two species. In conclusion, our results illustrate the
      diversification mechanism of organisms through the interaction with space and
      environment. Our results also present an ENM approach for identifying the key
      factors affecting demographic history and population structures of target
      species, especially endangered species.

PMID- 22990313
TI  - The genetics of obligate parthenogenesis in an aphid species and its consequences
      for the maintenance of alternative reproductive modes.
AB  - Although loss of sex is widespread among metazoans, the genetic mechanisms
      underlying the transition to asexuality are poorly understood. Aphids are good
      models to address this issue because they frequently show reproductive-mode
      variation at the species level, involving cyclical parthenogens (CP) that
      reproduce sexually once a year and obligate parthenogens (OP) that reproduce
      asexually all year round. Here, we explore the genetic basis of OP in the cereal
      aphid Sitobion avenae by crossing several genotypes with contrasting reproductive
      modes and then characterising the reproductive phenotypes of F1 and F2 offspring.
      The analysis of phenotypic variation in F1 and F2 progenies suggests that at
      least two autosomal loci control OP in S. avenae. First, the transition to
      asexuality seems to depend on a single recessive locus, because the offspring
      from self-crossed cyclical parthenogenetic genotypes contain either 0 or 25% OP.
      Second, as we observed OP in the F1 progenies from crosses between CP and OP, and
      some CP in the offspring from outcrossed OP, a dominant 'suppressor' gene may
      also be involved, being inactive when in a recessive homozygous state in CP; this
      is the most parsimonious explanation for these results. This oligogenic
      inheritance of OP in S. avenae appears to be an efficient genetic system to
      generate new OP genotypes continually. It also allows asexuality-inducing alleles
      to be protected locally during harsh winters when extreme frost kills most OP,
      and then to spread very quickly after winter.

PMID- 22990311
TI  - Detecting the footprints of divergent selection in oaks with linked markers.
AB  - Genome scans are increasingly used to study ecological speciation, providing a
      useful genome-wide perspective on divergent selection in the presence of gene
      flow. Here, we compare current approaches to detect footprints of divergent
      selection in closely related species. We analyzed 192 individuals from two
      interfertile European temperate oak species using 30 nuclear microsatellites from
      eight linkage groups. These markers present little intraspecific differentiation
      and can be used in combination to assign individual genotypes to species. We
      first show that different outlier detection tests give somewhat different
      results, possibly due to model constraints. Second, using linkage information for
      these markers, we further characterize the signature of divergent selection in
      the presence of gene flow. In particular, we show that recombination estimates
      for regions with outlier markers are lower than those for a control region, in
      line with a prediction from ecological speciation theory. Most importantly, we
      show that analyses at the haplotype level can distinguish between truly divergent
      (bi-directional) selection and positive selection in one of the two species,
      offering a new and improved method for characterizing the speciation process.

PMID- 22990314
TI  - Clinical predictors of sustained intraocular pressure elevation due to
      intravitreal anti-vascular endothelial growth factor therapy.
AB  - PURPOSE: We assess for frequency and predictive factors related to sustained
      intraocular pressure (IOP) elevation in eyes with neovascular age-related macular
      degeneration receiving intravitreal injections of ranibizumab and/or bevacizumab.
      METHODS: A total of 328 patients with neovascular age-related macular
      degeneration (449 eyes) who presented to a single physician over a 6-month period
      were retrospectively assessed for baseline demographic/clinical information,
      total number of bevacizumab and/or ranibizumab injections, and sustained IOP
      elevation on 2 or more consecutive visits (absolute IOP >25 mmHg, increase above
      baseline >10 mmHg, or IOP of >21 mmHg and increase of >5 mmHg). Cox regression
      survival analysis and multivariate logistic regression were performed to assess
      the influence of intravitreal injections on experiencing sustained IOP elevation.
      RESULTS: Overall, 32 eyes (7.1%) experienced sustained IOP elevation. Survival
      analysis showed a significant effect of the number of anti-vascular endothelial
      growth factor injections on sustained IOP elevation (hazard ratio, 1.085; 95%
      confidence interval: 1.06-1.11, P < 0.001). Also, there was an increased odds
      ratio (16.1, P = 0.008) of sustained IOP elevation in eyes receiving >=29
      injections compared with <=12 injections. After controlling for the confounder
      (prior intravitreal steroid injection), total number of injections still showed a
      statistically significant association (P = 0.002). CONCLUSION: A greater number
      of intravitreal anti-vascular endothelial growth factor injections is associated
      with an increased risk for sustained IOP elevation in eyes with neovascular age
      related macular degeneration receiving intravitreal ranbizumab and/or
      bevacizumab.

PMID- 22990315
TI  - Intravitreal pegaptanib sodium (Macugen) for treatment of myopic choroidal
      neovascularization: a morphologic and functional study.
AB  - BACKGROUND: To report the morphologic and functional outcomes resulting from the
      use of intravitreal pegaptanib (IVP) sodium (Macugen) in patients with myopic
      choroidal neovascularization. METHODS: An open-label, nonrandomized, prospective
      clinical trial was performed. Morphologic outcome, such as foveal thickness, was
      assessed by optical coherence tomography, whereas functional outcomes were
      assessed by best-corrected visual acuity and microperimetry. Treatment protocol
      consisted of 3 consecutive IVP (0.3 mg/0.05 mL; baseline, 6th week, and 12th
      week). Follow-up checks were scheduled at the following intervals: baseline, 18,
      24, 36, and 48 weeks. RESULTS: Twenty eyes from 20 patients were studied. All
      patients completed follow-up at 48 weeks. After IVP, a significant decrease in
      foveal thickness occurred (-20%), and at the end of follow-up, choroidal
      neovascularization closure was obtained in all eyes. An improvement of functional
      parameters was recorded in all patients (best-corrected visual acuity from 25.5
      +/- 8.09 letters to 45.5 +/- 8.16 letters, P < 0.0001; microperimetry from 8.40
      +/- 2.14 dB to 10.8 +/- 2.05 dB, P < 0.01). The mean number of IVP was 3, and
      none of patients met the re-treatment criterion during the entire follow-up
      period. Neither ocular nor systemic side effects were observed. CONCLUSION: The
      findings demonstrate that the selective inhibition of VEGF-165 isoform by IVP is
      an effective treatment for myopic choroidal neovascularization.

PMID- 22990316
TI  - Influence of intraocular tamponade on unintentional retinal displacement after
      vitrectomy for rhegmatogenous retinal detachment.
AB  - PURPOSE: To investigate the relationship between type of intraocular tamponade
      and unintentional retinal displacement after vitrectomy for rhegmatogenous
      retinal detachment. METHODS: Twenty-three eyes of 23 consecutive patients
      affected by rhegmatogenous retinal detachment underwent 3-port pars plana
      vitrectomy with gas (C3F8) or silicone oil (polydimethylsiloxane) tamponade.
      Ophthalmologic examination and fundus autofluorescence were performed before
      surgery (baseline) and at the 7-day, 1-month, and 3-month postoperative visits.
      Macula sparing rhegmatogenous retinal detachment underwent fixation test (with
      microperimetry) at baseline and at the 7-day and 1-month follow-up examinations.
      RESULTS: Fundus autofluorescence revealed postoperative retinal displacement in
      12 of the 23 eyes (52.2%). Occurrence of retinal displacement was higher in eyes
      with gas tamponade (10 of 14 eyes; 71.4%) compared with eyes with silicone oil (2
      of 9 eyes; 22.2%) (P = 0.036). Retina shifted downward in all eyes with C3F8 and
      upward in all eyes with polydimethylsiloxane. Baseline and follow-up macular
      fixation was tested in 10 macula-on cases. In all cases, a shift of mean fixation
      point was present at the 7-day postoperative examination, with a partial return
      toward the baseline mean fixation point at the 1-month follow-up examination.
      CONCLUSION: In eyes with rhegmatogenous retinal detachment treated with
      vitrectomy and gas or silicone oil tamponade, retinal displacement may occur
      despite successful reattachment. Type of intraocular tamponade seems to influence
      the occurrence of retinal dislocation and its direction.

PMID- 22990317
TI  - Assessment of the differences in pharmacokinetics and pharmacodynamics between
      four distinct formulations of triamcinolone acetonide.
AB  - PURPOSE: To compare the durability of Kenalog, Trivaris, Triesence, and
      compounding pharmacy preservative-free triamcinolone acetonide in pigmented
      rabbits with syneretic vitreous using direct visualization, pharmacodynamics, and
      pharmacokinetics. METHODS: Twenty-five Dutch-belted rabbits were used.
      Pharmacokinetic experiment: Rabbits were intravitreally injected with one of four
      4-mg triamcinolone acetonide formulations. Wide-field imaging was serially
      performed to document residual drug mass. Pharmacodynamics experiment: Four
      triamcinolone acetonide groups and one control group received intravitreal
      recombinant human vascular endothelial growth factor 165 every 2 weeks and were
      followed with fluorescein angiography to assess vascular endothelial growth
      factor retinal vasculopathy as a measure of residual steroid effect. Particle
      size of the formulations was measured with Mastersizer 2000. RESULTS: Remaining
      triamcinolone acetonide mass after 19 weeks: 12,091 +/- 2,512 pixels for the
      Kenalog group, 1,307.36 +/- 695.57 for Trivaris, 5577 +/- 1477 for Triesence, and
      1,535 +/- 329 for compounded preservative-free triamcinolone acetonide. Kenalog
      suppressed recombinant human vascular endothelial growth factor-induced
      retinopathy more effectively than the other triamcinolone acetonide groups at
      Week 39, the final time point assessed. Particle size (90th percentile) was 47
      MUm for Kenalog, 26 MUm for Triesence, and 22 MUm for both compounded
      preservative-free triamcinolone acetonide and Trivaris. CONCLUSION: Triamcinolone
      acetonide formulations do not have the same pharmacokinetics/pharmacodynamics.
      Kenalog has the longest vitreous visibility and durability. Particle size appears
      to correlate with efficacy and durability.

PMID- 22990318
TI  - Posterior hyaloid detachment and internal limiting membrane peeling assisted by
      anthocyanins from acai fruit (Euterpe oleracea) and 10 other natural vital dyes:
      experimental study in cadaveric eyes.
AB  - PURPOSE: The purpose of this study was to determine whether natural dyes
      facilitate posterior hyaloid detachment (posterior vitreous detachment [PVD]) and
      retinal internal limiting membrane (ILM) peeling in human eyes. METHODS: Open-sky
      vitrectomy with posterior hyaloid and ILM removal was performed in 86 human
      cadaveric eyes. After core vitrectomy, 11 different dyes were injected into the
      vitreous cavity to aid hyaloid detachment and ILM removal. The dyes were allowed
      to settle on the macula for 5 minutes after PVD and were removed by mechanical
      aspiration. Intraocular forceps were used for ILM peeling, which was confirmed by
      light microscopy of the peeled tissue. Acai fruit (Euterpe oleracea) extract and
      10 additional dyes from plants or animal sources were tested: pomegranate (Punica
      granatum), logwood (Haematoxylum campechianum), chlorophyll extract from alfalfa
      (Medicago sativa), cochineal (Dactylopius coccus), hibiscus (Hibiscus rosa
      sinensis), indigo (Indigofera tinctoria), paprika (Capiscum annuum), turmeric
      (Curcuma longa), old fustic (Maclura tinctoria), and grape (Vitis vinifera).
      RESULTS: The dyes facilitated PVD and ILM peeling. Acai fruit (E. oleracea)
      extract, logwood (H. campechianum), cochineal (D. coccus), and old fustic (M.
      tinctoria) facilitated PVD in all cases; dye-assisted PVD was compared with
      triamcinolone-assisted PVD performed previously in a comparative model. Acai
      fruit (E. oleracea) extract, cochineal (D. coccus), and chlorophyll extract from
      alfalfa (M. sativa) showed the best capability for ILM staining; dye-assisted ILM
      removal was compared with the ILM peeling guided by indocyanine green staining
      performed previously in a comparative model. Light microscopy confirmed the ILM
      removal in all cases. CONCLUSION: Anthocyanin dye of the acai fruit (E. oleracea)
      and the dyes from cochineal (D. coccus) and chlorophyll extract from alfalfa (M.
      sativa) resulted in the best capability for posterior hyaloid and ILM staining in
      human cadaveric eyes and may be a useful tool for vitreoretinal surgery.

PMID- 22990319
TI  - Intravitreal ranibizumab for polypoidal choroidal vasculopathy in non-Asian
      patients.
AB  - PURPOSE: To determine safety, tolerability, and efficacy of intravitreal
      ranibizumab in the treatment of polypoidal choroidal vasculopathy in a non-Asian
      population. METHODS: Phase I/II, prospective, open-label, single-center,
      nonrandomized, uncontrolled, consecutive, interventional case series of 20 eyes
      in 19 patients with exudative active polypoidal choroidal vasculopathy. Eyes
      received 3 monthly intravitreal ranibizumab injections (0.3 or 0.5 mg), with
      additional ranibizumab injections, observation, or alternative treatments at
      investigators' discretion, through 24 months. Main outcome measures were ocular
      and systemic safety and mean change from baseline in best-corrected visual acuity
      and center point thickness. RESULTS: Visually significant ocular adverse events
      included cataract progression (n = 3), mild vitreous hemorrhage (n = 2), and
      macular hole (n = 1). No systemic drug-related adverse events were observed. Mean
      baseline best-corrected visual acuity was 20/127 (range, 20/16-20/500) and center
      point thickness was 298 MUm. Mean best-corrected visual acuity increased from
      baseline by 1.2 Snellen lines at 12 months and 24 months. Mean center point
      thickness decreased by 53 MUm and 67 MUm from baseline at 12 months and 24
      months, respectively. CONCLUSION: Intravitreal ranibizumab was well tolerated in
      non-Asian patients with polypoidal choroidal vasculopathy; the majority of eyes
      experienced improvements in best-corrected visual acuity and center point
      thickness after ranibizumab treatment.

PMID- 22990320
TI  - Subthreshold transpupillary thermotherapy in management of foveal subretinal
      fluid in small pigmented choroidal lesions.
AB  - PURPOSE: To evaluate the effect of subthreshold transpupillary thermotherapy
      (sTTT) in foveal subretinal fluid of small pigmented choroidal lesions. METHODS:
      Retrospective, noncomparative, interventional case series. We reviewed patients
      with small pigmented choroidal lesions presenting foveal subretinal fluid and
      treated with sTTT to evaluate fluid regression. RESULTS: We treated 13 patients
      with small pigmented choroidal lesions with a mean height of 2.02 +/- 0.54 mm
      (range, 1.4-2.9 mm) and a mean largest diameter of 7.60 +/- 1.98 mm (range, 5-11
      mm). In 11 cases, foveal subretinal fluid was completely resolved (84.6%), with a
      mean follow-up of 42.46 +/- 26.29 months (range, 12-103 months). The mean number
      of sTTT sessions applied was 1.38 +/- 0.77 (range, 1-3 sessions), at a mean spot
      size of 1,570.59 +/- 795.1 MUm (range, 500-3,000 MUm), and overall exposure time
      of 2.32 +/- 1.2 minutes (range, 1-6 minutes). Mean laser power applied was 370.63
      +/- 162.87 mW (range, 200 to 600 mW). Best-corrected visual acuity at the time of
      diagnosis was maintained or improved in 69.3% of patients after sTTT treatment.
      During follow-up, tumor progression was reported in 5 cases, regardless of the
      presence of subretinal fluid. These cases were treated promptly with
      brachytherapy. CONCLUSION: However, sTTT may be effective in solving foveal
      subretinal fluid in small pigmented choroidal lesions, attaining satisfactory
      visual acuity in most cases.

PMID- 22990321
TI  - The longitudinal changes of retinal nerve fiber layer thickness after panretinal
      photocoagulation in diabetic retinopathy patients.
AB  - PURPOSE: To investigate longitudinal changes in retinal nerve fiber layer (RNFL)
      thickness after panretinal photocoagulation (PRP) in diabetic retinopathy
      patients. METHODS: This prospective study examined 31 eyes in 25 patients
      undergoing PRP, who were diagnosed with severe nonproliferative diabetic
      retinopathy or non-high-risk proliferative diabetic retinopathy. Optical
      coherence tomography was conducted before PRP and at 3, 6, 12, and 24 months
      after PRP to investigate changes in peripapillary RNFL thickness. RESULTS:
      Superior, nasal, inferior, temporal, and mean peripapillary RNFL thickness
      increased until 6 months after PRP and then decreased. Superior RNFL thickness
      increased significantly at 3 and 6 months and decreased significantly at 24
      months compared with the baseline RNFL thickness. Nasal RNFL thickness declined
      significantly at 24 months compared with the baseline RNFL thickness without any
      significant increase in thickness during the follow-up period. Inferior RNFL
      thickness increased significantly at 6 months and decreased significantly at 24
      months compared with its baseline RNFL thickness. Temporal thickness increased
      significantly at 3, 6, 12, and 24 months compared with the baseline RNFL
      thickness. Mean RNFL thickness increased significantly at 6 months and decreased
      significantly at 24 months. Central subfield thickness increased significantly at
      3, 6, 12, and 24 months compared with its baseline thickness. CONCLUSION:
      Peripapillary RNFL thickness increased at 6 months after PRP and then decreased
      at 24 months after PRP compared with baseline peripapillary RNFL thickness in
      diabetic retinopathy patients. This finding suggests that in addition to diabetes
      itself, diabetic retinopathy, and associated glaucoma, PRP may be a cause of RNFL
      thickness loss in patients with diabetes.

PMID- 22990323
TI  - Timing of acute macula-on rhegmatogenous retinal detachment repair.
AB  - PURPOSE: To determine if same-day or next available surgery changed the outcome
      of patients presenting with acute macula-on rhegmatogenous retinal detachments.
      METHODS: A retrospective review of patients presenting with acute macula-on
      rhegmatogenous retinal detachments treated with small-gauge vitrectomy was
      performed. Data collection included subjects' demographics, duration of symptoms,
      location and extent of the retinal detachment, and timing of surgery. The primary
      outcome was anatomical and functional success rate for patients having same-day
      surgery compared with those for whom surgery was delayed. RESULTS: One hundred
      and fourteen patients were included in this study. Sixty-two patients operated on
      day of presentation, 46 patients operated the day after presentation, and in 6
      patients, surgery was delayed from 2 to 5 days. Time to surgery in hours ranged
      between 1 and 120 hours (mean 14.5 +/- 15.05 hours). Retinal reattachment was
      achieved in 95.6% of patients, with 80% requiring only one procedure. Mean
      initial visual acuity was logarithm of the minimum angle of resolution 0.42 (SD
      0.6), and mean final visual acuity was logarithm of the minimum angle of
      resolution 0.39 (SD 0.67) (P = 0.53). Time to surgery was not found to effect
      final anatomical outcome (P = 0.56). No statistically significant association was
      observed between change in visual acuity and time to surgery (P = 0.99).
      CONCLUSION: Modest delay in timing of surgery for macula-on rhegmatogenous
      retinal detachment did not adversely impact on patients' outcome.

PMID- 22990322
TI  - Efficacy of anti-vascular endothelial growth factor therapy in subretinal
      neovascularization secondary to macular telangiectasia type 2.
AB  - PURPOSE: To evaluate the efficacy of intravitreal anti-vascular endothelial
      growth factor monotherapy in the treatment of naive subretinal neovascular
      membrane (SRNVM) secondary to macular telangiectasia (Mactel) Type 2. METHODS: A
      retrospective chart review of consecutive patients with naive SRNVM secondary to
      Mactel who were examined between January 2007 and April 2011 was performed. Eyes
      with diabetic retinopathy, age-related macular degeneration, or any other macular
      pathology were excluded. Demographic data, medical history, and ocular history
      were recorded. The mean change in best-corrected visual acuity at the final visit
      was the primary outcome measure. The mean number of intravitreal injections,
      retinal thickness on optical coherence tomography, and intraocular pressure were
      the secondary outcomes. RESULTS: A total of 16 eyes of 16 patients were included
      in the study. Of 16 eyes, 4 were treated with intravitreal ranibizumab
      monotherapy and 12 with intravitreal bevacizumab monotherapy. The average follow
      up duration was 12 months (range, 3-43 months). The mean baseline visual acuity
      was 0.17 +/- 0.16 (Snellen equivalent 20/120) (range, 0.001-0.5), and the mean
      final visual acuity was 0.27 +/- 0.14 (Snellen equivalent 20/70) (range, 0.05
      0.66), and this difference was statistically significant (P = 0.02). The mean
      number of intravitreal injections was 1.9 (range, 1-3), and there were no
      injection-related complications. CONCLUSION: Intravitreal anti-vascular
      endothelial growth factor monotherapy appears to be effective and safe in
      treatment-naive SRNVM secondary to Mactel.

PMID- 22990324
TI  - Retinal toxicity of intravitreal rituximab in albino rabbits.
AB  - PURPOSE: To evaluate retinal toxicity of intravitreal rituximab. METHODS: Twelve
      albino rabbits were included in the study. 1 mg/0.1 mL of rituximab was injected
      to the right (experimental) eye of each rabbit, and 0.1 mL of saline was injected
      into the left (control) eye. Electroretinogram was recorded before injection and
      3 hours, 4 days, 1 week, 2 weeks and 4 weeks after injection (12 rabbits), and
      visual evoked potential was recorded before injection and 4 weeks after injection
      (10 rabbits). Histology and glial fibrillary acidic protein immunocytochemistry
      (12 rabbits) were performed at 4 weeks after injection. Clinical examination was
      conducted at all time points in all rabbits. RESULTS: The average dark-adapted
      electroretinogram b-wave Vmax ratios, and the average light-adapted b-wave
      amplitude ratios were approximately 1, and the average log sigma difference was
      around zero throughout the follow-up period. The average visual evoked potential
      amplitude ratio and the average visual evoked potential implicit time difference
      were approximately 1 and 0, respectively. No histologic damage was seen, but
      glial fibrillary acidic protein was mildly expressed in 6 of 12 experimental
      eyes. Results of clinical examination were normal in all the eyes. CONCLUSION:
      Intravitreal injection of 1 mg rituximab does not cause functional or histologic
      signs of retinal toxicity in albino rabbits. Mild glial fibrillary acidic protein
      expression in Muller cells probably indicates a mild degree of retinal stress.

PMID- 22990325
TI  - Allicin ameliorates cardiac hypertrophy and fibrosis through enhancing of Nrf2
      antioxidant signaling pathways.
AB  - AIM: To evaluate the protective effects of allicin on Ang II-induced cardiac
      hypertrophy. METHODS: Sprague-Dawley male rats were randomized into 3
      groups:1)sham group (saline)(n = 12), 2) Ang II group(n = 9), 3) allicin group
      (Ang II + allicin)(n = 9). They received infusions of either saline or Ang II
      (250 ng/kg body weight per min) through mini-osmotic pumps implanted
      subcutaneously for 2 weeks and given a diet containing 180 mg/kg/day of allicin
      for 8 consecutive weeks. Hemodynamic, morphological, histological, and
      biochemical changes were evaluated at corresponding time points. RESULTS: Ang II
      infusion increased blood pressure, heart rate and heart weight to body weight
      ratio, and resulted in anatomical and functional changes, such as increased LV
      mass, posterior wall thickness and LV end-diastolic diameter, and decreased
      fractional shortening and EF compared with sham rats. Nrf2 and HO-1 in the hearts
      of rats in the Ang II group were moderately elevated at both mRNA and protein
      levels compared to sham group mice, but NQO1 andgamma-GCS were significantly
      lower. GPx activities, levels of GSH and T-AOC in the hearts of the rats in the
      Ang II group were also significantly lower, and the levels of TBARS, reactive
      oxygen species and protein carbonyl were significant increased. Allicin
      attenuated LV mass, posterior wall thickness and LV end-diastolic diameter (1.10
      +/- 0.04 vs. 1.37 +/- 0.05, 2.26 +/- 0.08 vs. 2.96 +/- 0.12, 7.27 +/- 0.36 vs.
      8.56 +/- 0.41, respectively; all P < 0.05), and increased fractional shortening
      and EF (28.30 +/- 3.21 vs. 25.40 +/- 2.57, 60.27 +/- 5.63 vs. 51.30 +/- 4.78,
      respectively; both P < 0.05) in the Ang II-induced hypertrophic rats compared to
      the untreated Ang II rats. Furthermore, allicin treatment attenuated the
      accumulation of interstitial collagen and collagen I/III (P < 0.01 vs. the
      untreated Ang II group), decreased the levels of reactive oxygen species, protein
      carbonyl and TBARS and increased GPx activities. Moreover, allicin significantly
      increased mRNA expression and protein levels of Nrf2, NQO1, and gamma-GCS ( P <
      0.01, P < 0.05 vs. the untreated Ang II group). CONCLUSION: Allicin could prevent
      the development of cardiac remodeling and the progression of cardiac hypertrophy
      to cardiac dysfunction caused by enhancing the Nrf2 antioxidant signaling
      pathways.

PMID- 22990326
TI  - Pnicogen-pi complexes: theoretical study and biological implications.
AB  - The energetic and geometric features of pnicogen-pi complexes involving different
      types of aromatic rings (benzene, trifluorobenzene, hexafluorobenzene and s
      triazine) and the heavier pnicogenes (ECl(3), E = As, Sb, Bi) are investigated
      using theoretical methods (ab initio and DFT-D3). We have analyzed how the
      interaction energy is affected by the pi-acidity of the aromatic moieties and the
      pnicogen used. In addition, we have found several examples in the Protein
      Databank where pnicogen-pi interactions are present. This likely indicates the
      potential use of this interaction in the design and synthesis of potential
      inhibitors of enzymatic reactions. Moreover, in order to know the reliability of
      the latest version of dispersion termed corrected DFT-D3, we have also compared
      the energies obtained using the ab initio MP2 method with those obtained using
      BP86-D3. We have also computed and analyzed the dispersion contribution to the
      total interaction energy in order to know if it is crucial for the favourable
      binding. This allows a better understanding of the physical nature of the
      interaction. Finally, we have used the Bader's theory of "atoms-in-molecules" to
      demonstrate that the electron density computed at the bond critical point that
      emerges upon complexation can be used as a measure of bond order in this
      noncovalent interaction.

PMID- 22990327
TI  - Effect of cardiovascular drug classes on all-cause mortality among atrial
      fibrillation patients treated in primary care in Sweden: a cohort study.
AB  - BACKGROUND: Risk factors for stroke are well known in atrial fibrillation (AF)
      patients, while less is known on the effect of these factors on total mortality.
      OBJECTIVE: Our aim was to study the impact of cardiovascular drug classes on
      mortality in AF patients treated in primary care. METHODS: The study population
      was chosen based on patient data from 75 primary care centres in Sweden compiled
      in a database. Individuals diagnosed with AF who were older than 45 years were
      enrolled (n = 12,302, of whom 6,660 were men). Cox regression analysis with
      mortality (years to death) as outcome was conducted in the men and women
      separately, as well in the age categories <80 and >= 80 years, with
      cardiovascular drugs as independent factors, and age, cardiovascular diagnoses
      and educational level as covariates. RESULTS: Lower mortality was shown for
      anticoagulant treatment among men, both younger (<80 years) [adjusted hazard
      ratio (HR) 0.43, 95 % confidence interval (CI) 0.31-0.61] and older (>= 80 years)
      (adjusted HR 0.47, 95 % CI 0.32-0.69), and among younger women (adjusted HR 0.46,
      95 % CI 0.29-0.74), and for antiplatelet treatment in older men (adjusted HR
      0.51, 95 % CI 0.35-0.74). Treatment with thiazides was associated with lower
      mortality among younger men (adjusted HR 0.68, 95 % CI 0.48-0.96), older men
      (adjusted HR 0.67, 95 % CI 0.46-0.98) and older women (adjusted HR 0.70, 95 % CI
      0.52-0.94). Statins were associated with lower mortality among younger patients,
      in both men (adjusted HR 0.47, 95 % CI 0.32-0.68) and women (adjusted HR 0.54, 95
      % CI 0.35-0.82). CONCLUSIONS: The differences in age and gender patterns need
      further exploration.

PMID- 22990328
TI  - ACE inhibitors and ribavirin-associated cough: a common undefined predisposing
      factor?

PMID- 22990329
TI  - Application of the MAT-CHDSP to assess guideline adherence and therapy goal
      achievement in secondary prevention of coronary heart disease after percutaneous
      coronary intervention.
AB  - PURPOSE: Numerous studies have documented suboptimal adherence to guideline
      recommendations in secondary prevention of coronary heart disease (CHD(SP)).
      Clinical practice guidelines (CPGs) are continuously developed to define
      appropriate patient care, aiming to reduce risk of morbidity and death. The
      Medication Assessment Tool for CHD(SP) (MAT-CHD(SP)) was developed to assess
      adherence to CPGs concerning medication therapy and follow-up of patients with
      CHD(SP). The aim of this study was to explore whether the MAT-CHD(SP) could be
      applied retrospectively to assess guideline adherence and therapy goal
      achievement in secondary prevention of CHD. METHODS: We collected data from
      electronic medical records of all patients who underwent percutaneous coronary
      intervention with stent implantation from January to March 2008 (n = 300) and
      applied the MAT-CHD(SP). We measured time for data collection and MAT application
      and tested reproducibility by calculating Cohen's kappa (kappa) value for inter
      and intraobserver agreement. RESULTS: A total of 247 MAT applications were
      analyzed, showing overall applicability of 66 % of the 4,446 MAT-CHD(SP) criteria
      and a high reproducibility of MAT-CHD(SP) application (kappa values 0.93 and 0.95
      for intra- and interobserver agreement, respectively). Mean time for data
      collection and MAT-CHD(SP) application was 11 min. Adherence to criteria
      concerning prescription was high (>75 %), but achievement of therapy goals for
      cholesterol and blood pressure was low (<50 %). Documentation of lifestyle advice
      achieved intermediate (50-75 %) or low adherence, as did therapy amendments in
      patients in whom therapy goals were unachieved at hospital admission.
      CONCLUSIONS: The MAT-CHD(SP) offers a means to identify both adherence and
      nonadherence to CPGs concerning CHD(SP) is applicable in retrospective assessment
      of CHD(SP), and identifies potentials for improved patient care.

PMID- 22990330
TI  - Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two
      CYP3A4 model substrates, in healthy male subjects.
AB  - PURPOSE: Pre-clinical experiments have shown that almorexant, a dual orexin
      receptor antagonist, is able to inhibit cytochrome P450 3A4 (CYP3A4). Therefore,
      a study was conducted to investigate the effects of multiple-dose almorexant on
      the pharmacokinetics of midazolam and simvastatin, two CYP3A4 model substrates.
      METHODS: Fourteen healthy male subjects were enrolled in an open-label,
      randomized, two-way crossover study. Treatment period A consisted of a single
      oral dose of 2 mg midazolam on day 1 and 40 mg simvastatin on day 3. In treatment
      period B, subjects received 200 mg almorexant once daily for 9 days together with
      a single oral dose of midazolam on day 7 and simvastatin on day 9. RESULTS:
      Concomitant administration of midazolam with almorexant at steady-state levels,
      achieved within 4-5 days, resulted in an increase of 1.2-fold [90 % confidence
      interval (CI) 1.0-1.4], 1.4-fold (90 % CI 1.2-1.6), and 1.3-fold (90 % CI 1.2
      1.4) in the maximum plasma concentration (C(max)), area under the concentration
      time curve from time 0 to infinity (AUC(0-infinity)), and terminal half-life
      (t(1/2)), respectively, of midazolam; the time to peak plasma concentration
      (t(max)) was unchanged. Whereas C(max) and t(max) were not influenced by
      almorexant, the AUC(0-infinity) of hydroxy-midazolam increased by 1.2-fold (90 %
      CI 1.1-1.4) and the t(1/2) by 1.3-fold (90 % CI 1.0-1.5). Concomitant
      administration of simvastatin with almorexant at steady-state resulted in an
      increase of 2.7-fold (90 % CI 2.0-3.7) and 3.4-fold (90 % CI 2.6-4.4) in C(max)
      and AUC(0-infinity), respectively, for simvastatin; the t(1/2) and t(max) were
      unchanged. The C(max) and AUC(0-infinity) of hydroxyacid simvastatin both
      increased by 2.8-fold, with 90 % CIs of 2.3-3.5 and 2.2-3.5, respectively; the
      t(max) increased by 2 h and the t(1/2) was unchanged. The urinary 6-beta
      hydroxycortisol/cortisol ratio was unaffected by almorexant. CONCLUSIONS: Our
      results suggest that the observed interaction was caused by the inhibition of
      CYP3A4 activity, most probably at the gut level.

PMID- 22990332
TI  - Over-expression of vascular endothelial growth factor in pituitary adenomas is
      associated with extrasellar growth and recurrence.
AB  - Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion
      and recurrences. Angiogenesis is regarded as an essential step in the formation
      of solid tumors. The aim of this study is to find out whether angiogenic factors
      may have information about the aggressiveness of PA that could be useful in
      determining the frequency of follow-up and whether adjuvant therapy is necessary.
      In this retrospective descriptive study, we evaluated vascular endothelial growth
      factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46
      human PA samples. Clinical data, histological subtype and radiologic
      characteristics were studied to determine the associations between the variables
      and the pre-operative behavior of the tumor. In addition, we monitored 12
      patients without adjuvant post-operative therapies over 46 months after surgery,
      determining progression of tumor remnants and its association with these markers.
      VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF
      demonstrates different expression between histological subtypes (p = 0.036). The
      extension at magnetic resonance imaging showed that VEGF expression was related
      to suprasellar extension (p = 0.007), being expressed more on tumors with
      extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a
      27.5 times increased risk of extrasellar growth when VEGF expression exceeds
      0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater
      than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results
      suggest that the expression of VEGF and its receptor could be a marker for poor
      outcome after partial tumor resection. These data should be considered in future
      studies evaluating angiogenic factors as therapeutic targets in patients with PA.

PMID- 22990331
TI  - CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients
      on long-term anticoagulation.
AB  - OBJECTIVES: The main aim of this study was to determine whether CYP2C9 and VKORC1
      polymorphisms influence warfarin dose variability during initial dose-finding
      phase and during maintenance treatment after 360 days. METHODS: Two hundred and
      six consecutive patients who were beginning warfarin therapy were selected. They
      were assessed for general and clinical characteristics; prescribed warfarin dose;
      response to therapy on days 7-10, 30, 60, 180, and 360; adverse events; and
      CYP2C9 2, 3, 5, 6, 8, 11, and VKORC1 1639G >A assays. RESULTS: During the first
      30 days of anticoagulation, the relative variability of warfarin dose was
      significantly associated with CYP2C9*2 and CYP2C9*3 polymorphisms (p = 0.02) and
      with VKORC1 1639G >A genotypes (p = 0.04). Warfarin variability was also
      statistically different according to predicted metabolic phenotype and to VKORC1
      genotypes after 360 days of treatment, and in the phase between 180 and 360 days
      (long-term dose variability). Both CYP2C9 and VKORC1 polymorphisms were
      associated with the international normalized ratio (INR) made between 7 and 10
      days/initial dose ratio, adjusted for covariates (p < 0.01 and p = 0.02,
      respectively). Patients carrying VKORC1 and CYP2C9 variants presented lower
      required dose (at the end of follow-up of 360 days) compared to patients carrying
      wild-type genotypes (p = 0.04 and p = 0.03, respectively). CONCLUSIONS: Genetic
      information on CYP2C9 and VKORC1 is important both for the initial dose-finding
      phase and during maintenance treatment with warfarin.

PMID- 22990333
TI  - 3D nanomolding for lab-on-a-chip applications.
AB  - The ability to decorate microfluidic channel walls with additional
      micro/nanostructures becomes important as a means to modify the flow behavior,
      such as mixing and pressure drop, as well as to enhance the reactivity of bio
      reactions to the surface in lab-on-a-chip applications. Despite the ability of
      mass production at low cost, conventional micro and nanomolding techniques are
      limited to the patterning of planar or slightly curved polymer substrates. Here
      we show a two-step molding technique, named 3D nanomolding, which allows the
      patterning of arbitrarily hierarchical multiscale structures, even nanostructures
      formed on the vertical sidewalls of microfluidic channels. In the first molding
      step, an ultra-thin intermediate polydimethyl siloxane (PDMS) stamp is produced
      by spin-coating and curing PDMS prepolymer on a pre-nanopatterned poly(methyl
      methacrylate) (PMMA) substrate, which is followed by the second molding step
      using the primary PDMS stamp containing microstructures. Various hierarchical
      micro and nanostructures are demonstrated, which include a biomimetic
      superhydrophobic structure in a lotus leaf surface to modify the surface wetting
      property and microfluidic channels where the walls are patterned with
      nanostructures. Despite the presence of nanostructures on the top surface, 3D
      nanomolded microchannels could be sealed well with a nanopatterned PMMA cover
      plate using solvent bonding to form enclosed microfluidic devices. The results
      indicate that the 3D nanomolding technique is suitable for decorating
      microchannel walls for lab-on-a-chip applications.

PMID- 22990334
TI  - Secondary Budd-Chiari syndrome complicating calcified right atrial thrombosis
      related to ventriculoatrial shunt.

PMID- 22990335
TI  - Clinical and laboratory features dependent on age at onset in Japanese systemic
      sclerosis.
AB  - OBJECTIVE: To clarify those clinical characteristics dependent on patient age at
      onset of Japanese systemic sclerosis (SSc). METHODS: A total of 329 SSc patients
      treated at Kanazawa University Hospital were enrolled in the study and
      subsequently categorized into four subgroups depending on age at SSc onset:
      childhood-onset, young-onset, normal age-onset, and late-onset. The clinical
      features at the first visit were compared between groups. Factors that correlated
      with age at onset were also analyzed. RESULTS: The childhood-onset subgroup was
      characterized by a higher male:female ratio, higher anti-topoisomerase I antibody
      (Ab) and anti-U3 RNP Ab levels, a higher frequency of pitting scars, and a lower
      frequency of anticentromere Ab and interstitial lung disease (ILD). The young
      onset patients had an increased frequency of anti-U1 RNP Ab and anti-U3 RNP Ab,
      overlap with other connective tissue diseases, digital ulcers, and pitting scars
      and a reduced frequency of anticentromere Ab. Patients with late-onset SSc showed
      a shorter disease duration and an increased frequency of anti-RNA polymerase Ab.
      Multiple regression analysis showed that anti-topoisomerase I Ab, anti-U1 RNP Ab,
      pitting scars, and long disease duration were associated with onset at a younger
      age, whereas anticentromere Ab and ILD were associated with onset at an older
      age. CONCLUSIONS: The clinical phenotype of SSc in Japanese patients showed a
      tendency to be dependent on age at onset.

PMID- 22990336
TI  - Depression is improved when low-dose tacrolimus is given to rheumatoid arthritis
      patients showing an inadequate response to biologic agents.
AB  - PURPOSE: Depression in rheumatoid arthritis (RA) patients is more severe than in
      healthy people. Herein, we report improved depression in RA patients using
      biologic agents. We examined whether depression was improved by tacrolimus
      combination therapy when biologic agents were ineffective. METHOD: The study
      included 13 RA patients who used biologic agents. The following methods were used
      before the initiation of tacrolimus combination therapy and at 14 and 30 weeks
      after treatment initiation: the Zung self-rating depression scale (SDS) to
      evaluate depression state, disease activity score 28/erythrocyte sedimentation
      rate (DAS28), tender joint counts, swollen joint counts, a patient global
      assessment to evaluate RA disease activity, and the modified health assessment
      questionnaire (mHAQ) to evaluate quality of life. RESULTS: The SDS scores before
      the initiation of tacrolimus combination therapy and at 14 and 30 weeks after
      treatment initiation were 45.2 +/- 10.6, 44.8 +/- 12.8, and 41.6 +/- 11.2 (p =
      0.047), respectively, indicating significant improvement. The DAS28 was 5.0 +/-
      1.3 prior to treatment, 3.8 +/- 1.3 at 14 weeks, and 3.5 +/- 0.9 at 30 weeks,
      demonstrating significant improvement at both 14 and 30 weeks (p < 0.001). The
      mHAQ score changed from 0.60 +/- 0.45 at baseline to 0.54 +/- 0.52 and 0.38 +/-
      0.43 at 14 and 30 weeks, respectively. The mHAQ score was significantly lower at
      30 weeks when compared to baseline (p = 0.013). CONCLUSION: Tacrolimus
      combination therapy does not directly improve depression in RA patients, but it
      is possible that the observed improvement in depression accompanies the
      improvement in the secondary failure of RA.

PMID- 22990337
TI  - Physical diagnosis: the lost art.

PMID- 22990342
TI  - A View through Medicare's Looking Glass: Notices You Might Have Missed.
AB  - CMS has made great strides in supplying current coding,payment, and coverage
      information. Wound care providers must pick up the looking glass to view this
      important information that is released on a regular basis. If you have not
      subscribed to this valuable information, now is the time to act. The looking
      glass is there if you will only reach out for it.

PMID- 22990343
TI  - Pressure Ulcer Prevention Program Study: a randomized, controlled prospective
      comparative value evaluation of 2 pressure ulcer prevention strategies in nursing
      and rehabilitation centers.
AB  - OBJECTIVE: This article assesses the comparative prevention-effectiveness and
      economic implications of a Pressure Ulcer Prevention Program (PUPP) against
      standard practice of prevention using Agency for Health Care Policy and Research
      (now the Agency for Healthcare Research and Quality [AHRQ]) guidelines and a
      mixture of commercial products. DESIGN: The study is a randomized, controlled,
      prospective cohort study with an accompanying economic evaluation. The economic
      evaluation is performed from the perspective of the nursing and rehabilitation
      centers. SETTINGS: Two nursing and rehabilitation centers under the same quality
      and safety support organization. Both institutions are experiencing high nursing
      staff turnover and incidence of pressure ulcers (PrUs). PARTICIPANTS: 133
      residents at risk of developing PrUs (EQUIP-for-Quality Risk Score Moderate to
      Very High [MVH]). All are Medicare-eligible residents with Minimum Data Set (MDS)
      2.0 evaluations. INTERVENTIONS: The PUPP includes a strategic product bundle and
      decision algorithms driven by MDS 2.0 Resident Assessment Scores to assist in
      reducing or preventing PrUs and incontinence-associated skin conditions. The
      control group utilizes a different brand and assortment of commercial skin care
      products, briefs, pads, and mattresses, but without use of the decision
      algorithms driven by MDS 2.0 Resident Assessment Scores. Pressure ulcer
      prevention education was done for all nurses by a nurse certified in the PUPP
      program at the beginning and ad libitum by trained senior nursing staff at the
      end of the study. MAIN OUTCOME MEASURES: Comparative reduction in the incidence
      of nosocomial PrUs and average 6-month net cost savings per MVH-risk resident.
      METHODS: Residents were assessed for PrU risk using EQUIP-for-Quality risk
      assessment algorithm based on data from their Minimum Data Set (MDS 2.0), then
      assigned to either the PUPP program or control group (standard practice following
      AHRQ guidelines). Residents were followed until discharge, death, development of
      PrU, or a maximum time period of 6 months. Direct medical costs of prevention and
      PrU treatment were recorded using a modified activity-based costing method. A
      decision model was used to estimate the net cost savings attributed to the PUPP
      program over a 6-month period. RESULTS: A 67% reduction in the incidence of
      nosocomial pressure ulcers is attributable to the PUPP strategy over a 6-month
      period for MVH residents. The average 6-month cost for a MVH Medicare resident is
      $1928 and $1130 for the control group and PUPP group respectively. Mean
      difference (net cost savings per resident at risk of pressure ulceration) is $798
      per resident for PUPP. CONCLUSIONS: PUPP assisted in reducing the incidence of
      PrUs by 67% in a 6-month period in nursing home facilities. The estimated annual
      net cost savings attributed to PUPP for 300 MVH residents is estimated at
      approximately $240,000.

PMID- 22990344
TI  - Screening for the high-risk diabetic foot: a 60-second tool (2012).
AB  - People with diabetes mellitus will develop lower-limb complications, such as
      neuropathy, peripheral vascular disease, foot ulcers, and lower-leg amputations.
      Resources to control elevated hemoglobin A1c and blood pressure, along with the
      standardized approach using the 60-second tool (2012), can detect the high-risk
      diabetic foot and help prevent complications.

PMID- 22990346
TI  - Biofilm intervention pathway:  an idealized algorithm.

PMID- 22990347
TI  - In situ recyclable gold nanoparticles using CO2-switchable polymers for catalytic
      reduction of 4-nitrophenol.
AB  - CO(2)-switchable gold nanoparticles (AuNPs) were prepared by functionalizing
      AuNPs with CO(2)-switchable polymers. Their dispersion-re-dispersion in and
      separation from aqueous solution can be easily and reproducibly adjusted by CO(2)
      bubbling through and removal from the solution, enabling unique CO(2)
      controllable, efficient in situ recycling of NPs. As compared to non
      functionalized AuNPs, they exhibit higher catalytic activity (except for the 1st
      round), easier separation and better reusability for 4-nitrophenol reduction.

PMID- 22990348
TI  - Monte Carlo simulations for optimal light delivery in photodynamic therapy of non
      melanoma skin cancer.
AB  - The choice of light source is important for the efficacy of photodynamic therapy
      (PDT) of non-melanoma skin cancer. We simulated the photodynamic dose (PDD)
      delivered to a tumour during PDT using theoretical radiation transfer simulations
      performed via our 3D Monte Carlo radiation transfer (MCRT) model for a range of
      light sources with light doses up to 75 J cm(-2). The PDD delivered following
      superficial irradiation from (A) non-laser light sources, (B) monochromatic
      light, (C) alternate beam diameters and (D) re-positioning of the tumour within
      the tissue was computed. (A) The final PDD deposited to the tumour at a depth of
      2 mm by the Paterson light source was 2.75, 2.50 and 1.04 times greater than the
      Waldmann 1200, Photocure and Aktilite, respectively. (B) Tumour necrosis occurred
      at a depth of 2.23 mm and increased to 3.81 mm for wavelengths 405 and 630 nm,
      respectively. (C) Increasing the beam diameter from 10 to 50 mm had very little
      effect on depth of necrosis. (D) As expected, necrosis depths were reduced when
      the tumour was re-positioned deeper into the tissue. These MCRT simulations show
      clearly the importance of choosing the correct light source to ensure optimal
      light delivery to achieve tumour necrosis.

PMID- 22990349
TI  - Effects of physiotherapy interventions on balance in multiple sclerosis: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To determine the effects of physiotherapy interventions on balance in
      people with multiple sclerosis. DATA SOURCES: A systematic literature search was
      conducted in Medline, Cinahl, Embase, PEDro, both electronically and by manual
      search up to March 2011. STUDY SELECTION: Randomized controlled trials of
      physiotherapy interventions in people with multiple sclerosis, with an outcome
      measure linked to the International Classification of Functioning, Disability and
      Health (ICF) category of "Changing and maintaining body position", were included.
      DATA EXTRACTION: The quality of studies was determined by the van Tulder
      criteria. Meta-analyses were performed in subgroups according to the
      intervention. DATA SYNTHESIS: After screening 233 full-text papers, 11 studies
      were included in a qualitative analysis and 7 in a meta-analysis. The
      methodological quality of the studies ranged from poor to moderate. Low evidence
      was found for the efficacy of specific balance exercises, physical therapy based
      on an individualized problem-solving approach, and resistance and aerobic
      exercises on improving balance among ambulatory people with multiple sclerosis.
      CONCLUSION: These findings indicate small, but significant, effects of
      physiotherapy on balance in people with multiple sclerosis who have a mild to
      moderate level of disability. However, evidence for severely disabled people is
      lacking, and further research is needed.

PMID- 22990350
TI  - The 2012 John Swales lecture: questions unanswered - 30 years in the world of
      blood pressure.

PMID- 22990351
TI  - Effects of breathing frequency on baroreflex effectiveness index and spontaneous
      baroreflex sensitivity derived by sequence analysis.
AB  - AIMS: High-frequency paced breathing is required to avoid overestimation when
      measuring spectral baroreflex sensitivity (BRSLF) to predict outcomes in
      cardiovascular patients. We examined whether respiration should also be
      controlled when measuring the baroreflex effectiveness index (BEI) and baroreflex
      sensitivity (BRSseq), which are derived by sequence analysis. METHODS: We studied
      17 healthy young adults who breathed spontaneously and controlled their breathing
      to rates of 0.1, 0.2, 0.3 and 0.4  Hz in the supine position. We found
      respiratory influences on BEI and BRSseq depended on the lag used to pair the
      systolic arterial pressure and R-R interval in a sequence. Therefore, the two
      baroreflex measures were obtained by selecting the lag with a larger number of
      sequences for each section. RESULTS: BEI decreased progressively as the breathing
      frequency increased. BRSseq remained unchanged at rates of 0.1, 0.2 and 0.3  Hz,
      but was reduced during 0.4  Hz breathing. In contrast, BRSLF was constant during
      0.2, 0.3, and 0.4  Hz breathing, but was greater at 0.1  Hz. Rates of spontaneous
      breathing range from 0.1 to 0.32  Hz with a mean value of 0.19  Hz. Baroreflex
      measures obtained for spontaneous breathing were found to be between the values
      for 0.1 and 0.3  Hz paced breathing. CONCLUSION: BEI and BRSseq do not remain
      constant at various breathing frequencies. Nonetheless, considering the pattern
      of change and the frequency range of spontaneous respiration, the authors suggest
      that high-frequency paced breathing is not necessary when measuring the BEI and
      BRSseq under the conditions used in this study.

PMID- 22990352
TI  - Higher cardiovascular risk and impaired benefit of antihypertensive treatment in
      hypertensive patients requiring additional drugs on top of randomized therapy: 
      is adding drugs always beneficial?
AB  - BACKGROUND: In antihypertensive treatment trials, when randomized therapies do
      not reach target, additional drugs are administered. However, patients requiring
      (add-on) or not requiring add-on therapy (no-add-on) may be at different
      cardiovascular risk and differently susceptible to benefits of antihypertensive
      treatment. METHODS AND RESULTS: The Felodipine Event Reduction study included
      9711 Chinese hypertensive patients receiving 12.5  mg/day hydrochlorothiazide and
      randomized to associating either felodipine (5  mg/day) or placebo. Within 6
      months, add-on therapy (further diuretic and other drugs) was required by 2185
      patients, whereas 7243 did not require it. Despite significant SBP/DBP reductions
      by add-on therapy, outcome incidence remained much lower in no-add-on than in add
      on patients: hazard ratios for various outcomes, after adjusting for baseline
      variables and blood pressure (BP) at time of add-on decision, were 0.22-0.368 (P
      always <0.001) and remained substantially unchanged when further adjusted for the
      small SBP/DBP difference persisting during follow-up treatment (-2.4/-1.1  mmHg
      in no-add-on). When felodipine was compared to placebo, the benefit of a lower
      SBP/DBP caused by felodipine was evident in the no-add-on patients (hazard ratio
      0.45-0.68, P always <0.001), but it was lost in the add-on group (hazard ratio
      0.91-1.17). CONCLUSION: Comparing patients more or less easily responding to
      antihypertensive treatment may identify patients at high risk of outcomes and
      less susceptible to benefits of a lower BP. It remains to be more directly
      investigated to what extent adding drugs to drugs is effective in reducing
      outcomes of patients in whom simple antihypertensive therapy does not achieve
      goal BP.

PMID- 22990353
TI  - Ethnic and socioeconomic influences on childhood blood pressure:  the Child Heart
      and Health Study in England.
AB  - OBJECTIVES: Compared to UK white European adults, UK black African-Caribbean
      adults have higher mean SBP and DBP; UK South Asian adults have higher mean DBP
      but lower SBP. Information on blood pressure (BP) in UK children from different
      ethnic groups is limited. The aim of this study was to compare BP levels in UK
      children of black African-Caribbean, South Asian and white European origin.
      METHODS: BP and body build were measured in 5666 children in a cross-sectional
      study of UK primary school children of South Asian, black African-Caribbean and
      white European origin aged 9-10 years. Ethnic and socioeconomic differences in BP
      were obtained from multilevel linear regression models. RESULTS: After adjustment
      for height and adiposity, black African-Caribbean children had lower mean SBP
      than white Europeans [difference 1.62  mmHg, 95% confidence interval (CI) 0.86
      2.38  mmHg], whereas mean DBP was similar (difference 0.58  mmHg, 95% CI -0.12 to
      1.28  mmHg). The lower SBP was particularly marked in black African rather than
      Caribbean children (P  =  0.002). South Asian children had lower mean SBP
      (difference 1.10  mmHg, 95% CI 0.34-1.86  mmHg) than white Europeans and higher
      mean DBP (difference 1.07  mmHg, 95% CI 0.37-1.76  mmHg). The higher mean DBP was
      particularly marked among Indian and Bangladeshi, rather than Pakistani, children
      (P  =  0.01). BP was unrelated to socioeconomic circumstances; ethnic differences
      in BP were not affected by socioeconomic adjustment. CONCLUSION: A BP pattern
      similar to that in adults is present in UK South Asian but not in UK black
      African-Caribbean children at 9-10 years.

PMID- 22990354
TI  - Treatment and blood pressure control in Spain during 2002-2010.
AB  - OBJECTIVES: To examine the evolution of hypertension management and blood
      pressure (BP) control in Spain in the last decade across PRESCAP 2002, 2006 and
      2010. METHODS: The methodology of the three studies was the same. They were
      multicenter and cross-sectional surveys aimed to determine BP control rates in
      hypertensive patients in primary care in Spain during 2002, 2006 and 2010,
      respectively. In each study, patients at least 18 years, with an established
      diagnosis of hypertension were included. Adequate BP control was defined as BP
      less than 140/90 mmHg in the general population (<130/85 mmHg in PRESCAP 2002 and
      less than 130/80 mmHg in PRESCAP 2006 and PRESCAP 2010 for patients with
      diabetes, chronic kidney disease and cardiovascular disease). RESULTS: A total of
      12,754 patients (mean age 63.3 +/- 10.8 years; 57.2% women), 10,520 patients
      (64.6 +/- 11.3 years; 53.7% women) and 12,961 patients (66.3 +/- 11.4; 52.0%
      women) were included in PRESCAP 2002, PRESCAP 2006 and PRESCAP 2010 studies
      respectively. With regard to BP control rates, 36.1% [95% confidence interval
      (CI) 35.2-36.9%], 41.4% (95% CI 40.5-42.4%) and 46.3% of patients (95% CI 45.4
      47.1%) achieved BP goals in PRESCAP 2002, PRESCAP 2006 and PRESCAP 2010,
      respectively (P < 0.0001). In PRESCAP 2002, 56% of patients were on monotherapy,
      35.6% were taking two drugs and 8.4% at least three drugs. In PRESCAP 2006 these
      numbers were 44.4, 41.1 and 14.5%, respectively, and in PRESCAP 2010 they were
      36.4, 44.1 and 19.5%, respectively (P < 0.0001). CONCLUSION: BP control rates
      have improved in Spain from 2002 to 2010. This may be related, at least in part,
      with the higher use of antihypertensive treatment, particularly combined therapy.

PMID- 22990355
TI  - Systolic blood pressure lowering to 160 mmHg or less using nicardipine in acute
      intracerebral hemorrhage: a prospective, multicenter, observational study (the
      Stroke Acute Management with Urgent Risk-factor Assessment and Improvement
      Intracerebral Hemorrhage study).
AB  - OBJECTIVE: Optimal blood pressure (BP) control in acute intracerebral hemorrhage
      (ICH) remains controversial. We determined the effects of SBP lowering to 160
      mmHg or more using intravenous nicardipine for acute ICH patients. METHODS: This
      is a prospective, multicenter, observational study conducted in Japan, with the
      lack of control groups. Patients with supratentorial ICH within 3 h of onset,
      admission SBP 180 mmHg or more, Glasgow Coma Scale (GCS) 5 or more, and hematoma
      volume less than 60 ml were initially treated with intravenous nicardipine to
      maintain SBP between 120 and 160 mmHg with 24-h frequent BP monitoring. The
      primary endpoints were neurological deterioration within 72 h [GCS decrement >= 2
      points or National Institutes of Health Stroke Scale (NIHSS) increment >= 4
      points; estimated 90% confidence interval (CI) on the basis of previous studies:
      15.2-25.9%] and serious adverse effects (SAE) to stopping intravenous nicardipine
      within 24 h (1.8-8.9%). The secondary endpoints included hematoma expansion more
      than 33% at 24 h (17.1-28.3%), modified Rankin Scale (mRS) 4 or more (54.5-67.9%)
      and death at 3 months (6.0-13.5%). RESULTS: We enrolled 211 Japanese patients (81
      women, 65.6 +/- 12.0 years old). At baseline, BP was 201.8 +/- 15.7/107.9 +/-
      15.0 mmHg. Median hematoma volume was 10.2 ml (interquartile range 5.6-19.2), and
      NIHSS score was 13 (8-17). Neurological deterioration was identified in 17
      patients (8.1%), SAE in two (0.9%), hematoma expansion in 36 (17.1%), mRS 4 or
      more in 87 (41.2%), and death in four (1.9%). All the results were equal to or
      below the estimated lower 90% CI. CONCLUSION: SBP lowering to 160 mmHg or less
      using nicardipine appears to be well tolerated and feasible for acute ICH.

PMID- 22990356
TI  - Reference values of aortic pulse wave velocity in a large healthy population aged
      between 3 and 18 years.
AB  - OBJECTIVE: The measurement of aortic pulse wave velocity (PWV(ao)) is an accepted
      marker in stratifying individual cardiovascular risk in adults. There is an
      increasing volume of evidence concerning impaired vascular function in different
      diseases in paediatric populations, but, unfortunately, only a few studies are
      available on the measurement of normal PWV(ao) values in children. The aim of our
      study was to determine the reference values of PWV(ao) in a large healthy
      population using a newly developed technique. METHODS: Three thousand, three
      hundred and seventy-four healthy individuals (1802 boys) aged 3-18 years were
      examined by an invasively validated, occlusive, oscillometric device. RESULTS:
      The mean PWV(ao) values increased from 5.5 +/- 0.3 to 6.5 +/- 0.3 m/s (P < 0.05)
      in boys and from 5.6 +/- 0.3 to 6.4 +/- 0.3 m/s (P < 0.05) in girls. The
      increase, however, was not constant, and the values exhibited a flat period
      between the ages of 3 and 8 years in both sexes. The first pronounced increase
      occurred at the age of 12.1 years in boys and 10.4 years in girls. Moreover,
      between the ages of 3 and 8 years, the brachial SBP and mean blood pressures
      increased continuously and gradually, whereas the PWV(ao) remained unchanged. By
      contrast, beyond the age of 9 years, blood pressure and aortic stiffness trends
      basically moved together. CONCLUSION: Our study provides the largest database to
      date concerning arterial stiffness in healthy children and adolescents between
      the ages of 3 and 18 years, and the technology adopted proved easy to use in
      large paediatric populations, even at a very young age.

PMID- 22990357
TI  - Elevated troponin predicts long-term adverse cardiovascular outcomes in
      hypertensive crisis:  a retrospective study.
AB  - BACKGROUND: Hypertensive crisis is associated with poor clinical outcomes.
      Elevated troponin, frequently observed in hypertensive crisis, may be attributed
      to myocardial supply-demand mismatch or obstructive coronary artery disease
      (CAD). However, in patients presenting with hypertensive crisis and an elevated
      troponin, the prevalence of CAD and the long-term adverse cardiovascular outcomes
      are unknown. OBJECTIVE: We sought to assess the impact of elevated troponin on
      cardiovascular outcomes and evaluate the role of troponin as a predictor of
      obstructive CAD in patients with hypertensive crisis. METHODS: Patients who
      presented with hypertensive crisis (n = 236) were screened retrospectively.
      Baseline and follow-up data including the event rates were obtained using
      electronic patient records. Those without an assay for cardiac Troponin I (cTnI)
      (n = 65) were excluded. Of the remaining 171 patients, those with elevated cTnI
      (cTnI >= 0.12 ng/ml) (n = 56) were compared with those with normal cTnI (cTnI <
      0.12 ng/ml) (n = 115) at 2 years for the occurrence of major adverse cardiac or
      cerebrovascular events (MACCE) (composite of myocardial infarction, unstable
      angina, hypertensive crisis, pulmonary edema, stroke or transient ischemic
      attack). RESULTS: At 2 years, MACCE occurred in 40 (71.4%) patients with elevated
      cTnI compared with 44 (38.3%) patients with normal cTnI [hazard ratio: 2.77; 95%
      confidence interval (CI): 1.79-4.27; P < 0.001]. Also, patients with elevated
      cTnI were significantly more likely to have underlying obstructive CAD (odds
      ratio: 8.97; 95% CI: 1.4-55.9; P < 0.01). CONCLUSION: In patients with
      hypertensive crisis, elevated cTnI confers a significantly greater risk of long
      term MACCE, and is a strong predictor of obstructive CAD.

PMID- 22990358
TI  - The fetal origins of hypertension:  a systematic review and meta-analysis of the
      evidence from animal experiments of maternal undernutrition.
AB  - OBJECTIVE: Numerous experiments in animals have been performed to investigate the
      effect of prenatal undernutrition on the development of hypertension in later
      life, with inconclusive results. We systematically reviewed animal studies
      examining the effects of maternal undernutrition on SBP, DBP, and mean arterial
      blood pressure (BP) in offspring. METHODS: A search was performed in Medline and
      Embase to identify articles that reported on maternal undernutrition and
      hypertension in experimental animal studies. Summary estimates of the effect of
      undernutrition on SBP, DBP, and mean arterial BP were obtained through meta
      analysis. RESULTS: Of the 6151 articles identified, 194 were considered eligible
      after screening titles and abstracts. After detailed evaluation, 101 met the
      inclusion criteria and were included in the review. Both maternal general and
      protein undernutrition increased SBP [general undernutrition: 14.5 mmHg, 95%
      confidence interval (CI) 10.8-18.3; protein undernutrition: 18.9 mmHg, 95% CI
      16.1-21.8] and mean arterial BP (general undernutrition: 5.0 mmHg, 95% CI 1.4
      8.6; protein undernutrition: 10.5 mmHg, 95% CI 6.7-14.2). There was substantial
      heterogeneity in the results. DBP was increased by protein undernutrition (9.5
      mmHg, 95% CI 2.6-16.3), whereas general undernutrition had no significant effect.
      CONCLUSION: The results of this meta-analysis generally support the view that in
      animals, maternal undernutrition--both general and protein--results in increased
      SBP and mean arterial BP. DBP was only increased after protein undernutrition.
      The results depended strongly on the applied measurement technique and animal
      model.

PMID- 22990359
TI  - Rapid and biosecure diagnostic test for tuberculosis.
AB  - Early and rapid detection of the causative organism is necessary in tuberculosis.
      We present here an integrated and dedicated molecular biology system for
      tuberculosis diagnosis. One hundred and eighty-nine (189) biologic specimens from
      patients strongly suspected by clinical parameters of tuberculosis were studied
      by Ziehl-Neelsen staining, cultivation on a solid medium, and by a balanced
      heminested fluorometric PCR system (Orange G3TB) that preserves worker safety and
      produces a rather pure material free of potential inhibitors. DNA amplification
      was carried out in a low cost using a tuberculosis thermocycler-fluorometer. The
      double stranded DNA produced is fluorometrically detected. The whole reaction is
      carried out in one single tube which is never opened after adding the processed
      sample, thus minimizing the risk of cross contamination with amplicons. The assay
      is able to detect 30 bacilli/ml of sample having a 99.8 % inter-assay coefficient
      of variation. PCR was positive in 36 (18.9 %) tested samples (33 of them were
      smear-negative). In our study, it yields a preliminary overall sensitivity of
      97.4 %. In addition, its overall specificity is 98.7 %. The total run time of the
      test is 4 h with two and a half real working hours. All PCR-positive samples also
      had a positive result by microbiological culture and clinical criteria. The
      results obtained showed that it could be a very useful tool to increase
      efficiency in detecting the tuberculosis disease in low bacillus inoculum
      samples. Furthermore, its low cost and friendly usage make it feasible to be used
      in regions with poor development.

PMID- 22990360
TI  - Biorheological action of Ascaris lumbricoides larvae on human erythrocytes.
AB  - Previous studies have shown that A. lumbricoides extracts capture sialic acid
      (SA) from human red blood cells (RBC). The aim of this work was to study
      hemorheological alterations in vitro caused by parasite larvae. The
      biorheological action of three larva concentrates of first and second larval
      stage on group O erythrocytes was analyzed by incubating the erythrocyte packed
      together with an equal volume of larvae (treated RBC) and PBS (control RBC).
      Distribution and parameters of aggregation (digital image analysis), aggregation
      kinetics (erythroaggregameter), and viscoelasticity (erythrodeformeter) were
      measured. The digital image analysis showed that all the larvae diminished the
      isolated cells percentage and increased the size of the formed aggregates. The
      aggregate formation velocity was lower in the treated than in the control. The
      deformability index (ID) values of treated RBC did not present variations with
      respect to those of the control, but a decrease in the erythrocyte elastic
      modulus (MU(m)) and membrane surface viscosity (eta(m)) values was observed,
      indicating that the larvae not only induced a diminution in the membrane surface
      viscosity of RBC but also altered the dynamic viscoelasticity of the membrane.
      Experiments carried out in vitro support the conclusion that the contact between
      larvae and RBC produces hemorheological alterations.

PMID- 22990361
TI  - Circulating tumor cells (CTCs) detected by triple-marker EpCAM, CK19, and hMAM RT
      PCR and their relation to clinical outcome in metastatic breast cancer patients.
AB  - In order to investigate the prognostic value of circulating tumor cells (CTCs) in
      patients with metastatic breast cancer (MBC), the blood cells from 98 MBC
      patients and 60 controls were evaluated by RT-PCR to detect the presence of
      markers EpCAM, CK19, and hMAM. Peripheral blood was obtained from all patients
      with MBC before any systemic therapy. Immunofluorescence staining experiment was
      conducted on CTCs samples from 10 patients to investigate the coexpression of
      EpCAM, CK19, and hMAM. In addition, analyses were carried out for their
      correlation with patients' clinicopathologic features. EpCAM+, CK19+, and hMAM+
      cells were detected in 50 (51.0 %), 43 (43.9 %), and 68 (69.4 %) of the 98
      patients, respectively. Triple-marker-positive CTCs were detected in 86 of 98
      (87.8 %) patients with a significantly higher rate than the control group. Among
      the 98 patients, 12 (12.2 %) patients were negative for three genes, 34 (34.7 %)
      positive for one gene, 29 (29.6 %) positive for any two genes, and 23 (23.5 %)
      positive for all three genes. Compared to single-marker detection, the triple
      combined marker detection exhibited significantly higher rate. Furthermore, the
      specificity of triple combined markers of serial test was 100 %. The expression
      of three genes was significantly correlated with lymph node metastasis, high
      histological grade, and high levels of serum CA153 and CEA. Double
      immunofluorescence labeling confirmed the presence of following CTCs phenotypes:
      CK19+/hMAM+, CK19+/hMAM-, CK19-/hMAM+, CK19+/EpCAM+, CK19-/EpCAM+, CK19+/EpCAM-,
      hMAM+/EpCAM+, and hMAM+/EpCAM-. After 2 years of follow-up, the presence of CTCs
      with triple-marker positive in peripheral blood was an independent risk factor
      for reduced progression-free survival (PFS) and overall survival (OS), and the
      presence of CTCs before any chemotherapy predicts poor OS and PFS in patients
      with MBC.

PMID- 22990362
TI  - E1 reaction-induced synthesis of hydrophilic oxide nanoparticles in a non
      hydrophilic solvent.
AB  - In this paper, tert-amyl alcohol was employed to directly react with metal
      chlorides for the preparation of oxide nanoparticles. Some typical metal oxide or
      hydroxides with different morphologies, such as TiO(2) nanoparticles, TiO(2)
      nanorods, FeOOH nanowires, Fe(2)O(3) nanoparticles, and SnO(2) nanoparticles, can
      be easily fabricated through such simple chemical reactions. E1 reaction was
      found to play the leading role in the synthesis of metal oxides attributed to
      better stability of tertiary carbocations in tert-amyl alcohol and the strong
      interaction of metal chlorides with hydroxyl groups that results in the easy
      dissociation of carbon-oxygen bonds in tert-amyl alcohol. S(N)1 reaction can also
      occur in certain reactions due to nucleophilic substitution of chloride ions for
      hydroxyl groups. As-prepared metal oxides show good compatibility with an aqueous
      system while they were synthesized in a non-hydrophilic solvent probably
      attributed to the specific E1 reaction mechanism involving the generation of
      water, and can be directly incorporated into an aqueous soluble polymer, such as
      PVA, to exhibit many promising applications.

PMID- 22990363
TI  - Conversion and kinetics study of fructose-to-5-hydroxymethylfurfural (HMF) using
      sulfonic and ionic liquid groups bi-functionalized mesoporous silica
      nanoparticles as recyclable solid catalysts in DMSO systems.
AB  - Mesoporous silica nanoparticles functionalized with both sulfonic acid (HSO(3))
      and ionic liquid (ILs) were synthesized and applied as effective and recyclable
      catalysts for generating 5-hydroxymethylfurfural (HMF) from fructose. For the
      first time a high HMF yield of 72.5% was achieved in DMSO systems under mild
      conditions (90  degrees C and 3 h). We further studied the kinetics of the
      fructose-to-HMF conversion and compared the rate constants, reaction orders, and
      activation energies for the systems with and without bi-functional MSN catalysts.

PMID- 22990364
TI  - The incidence and clinical predictors of acute infarction in patients with
      transient ischemic attack using MRI including DWI.
AB  - INTRODUCTION: According to the most recent definition of transient ischemic
      attack (TIA) and the recommendations of the American Heart Association, magnetic
      resonance imaging (MRI) including diffusion-weighted imaging (DWI) is considered
      a mandatory tool in evaluating and treating patients with TIA. This study aims to
      determine the incidence of TIA-related acute infarction, identify the independent
      predictors of acute infarction, and investigate the correlation between acute
      infarction detected by DWI-MRI and stroke risk during hospitalization. METHODS:
      Over a 36-month period (starting November 2007), all TIA patients (symptom
      duration of <24 h) who were admitted to hospital within 48 h of symptom onset and
      who underwent DWI-MRI were included in this population-based prospective study.
      The incidence of acute infarction, clinical predictors, and association with
      stroke recurrence during hospitalization were studied. RESULTS: Of 1,910 patients
      (mean age, 66.7 +/- 13 years; 46 % women), 1,862 met the inclusion criteria. A
      TIA-related acute infarction was detected in 206 patients (11.1 %). Several
      independent predictors were identified with logistic regression analysis: motor
      weakness [odds ratio (OR), 1.5], aphasia (OR, 1.6), National Institutes of Health
      Stroke Scale (NIHSS) score of >=10 at admission (OR, 3.2), and hyperlipidemia
      (OR, 0.6). Of 24 patients (1.3 %) who suffered a stroke during hospitalization
      (mean, 6 +/- 4 days), five had positive DWI. Stroke rate during hospitalization
      was nonsignificantly higher in patients with positive DWI than those with
      negative DWI (2.4 vs 1.1 %, respectively; P = 0.12). CONCLUSION: The evidence of
      acute infarction by DWI-MRI in TIA patients was detected in 11.1 % of patients
      and associated with motor weakness, aphasia, and NIHSS score of >=10 at
      admission.

PMID- 22990365
TI  - Tumor necrosis factor-alpha-immunoreactive cells in nucleus pulposus in
      adolescent patients with lumbar disc herniation.
AB  - STUDY DESIGN: Immunohistochemistry for tumor necrosis factor (TNF)-alpha in
      nucleus pulposus of adolescent patients with lumbar disc herniation. OBJECTIVE:
      To examine whether an inflammatory cytokine is expressed in the nucleus pulposus
      of adolescent patients with lumbar disc herniation. SUMMARY OF BACKGROUND DATA:
      TNFalpha is thought to play a crucial role in the radicular pain caused by lumbar
      disc herniation in adult patients. However, the expression of TNFalpha in the
      nucleus pulposus of adolescent patients with lumbar disc herniation has not been
      explored. METHODS: Five samples of nucleus pulposus from adolescent patients with
      lumbar disc herniation (age, 12-16 yr; n = 5) or controls requiring surgery for
      other back problems (age, 12-16 yr; n = 4; nonpainful scoliosis) were harvested
      during surgery. Nucleus pulposus specimens were immunostained using TNFalpha
      antibodies and immunostained cells in the nucleus pulposus were counted. We
      compared the expression of TNFalpha between the 2 groups. RESULTS: In patients
      with lumbar disc herniation, more TNFalpha-immunoreactive cells were seen in the
      nucleus pulposus in comparison with patients with nonpainful scoliosis (P <
      0.01). CONCLUSION: The results suggest that TNFalpha may play a role in
      adolescent patients with lumbar disc herniation. The TNFalpha expression may be
      related with disc degeneration and pain in adolescent patients with lumbar disc
      herniation.

PMID- 22990366
TI  - Dual growing rods technique for congenital scoliosis:  more than 2 years
      outcomes: preliminary results of a single center.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate clinical outcomes of
      dual growing rod (GR) technique in treating children with congenital scoliosis
      (CS). SUMMARY OF BACKGROUND DATA: Published reports on the dual GR technique
      results of early-onset scoliosis demonstrate it to be safe and effective.
      However, the use of GR in congenital spinal deformities is controversial, and
      there have been no reports on the results and complications of dual GR technique
      for CS with large series of patients. METHODS: During 2004 to 2009, a total of 30
      patients with CS underwent dual GR procedures. Of the 159 total procedures
      conducted within the treatment period, 125 were lengthenings with an average of
      4.2 lengthenings per patient. Five patients with severe rigid deformity or
      kyphosis had an osteotomy at apex vertebra with short segmental fusion. The
      analysis included age at initial surgery and final fusion (if applicable), number
      and frequency of lengthenings, and complications. Radiographical evaluation was
      conducted. RESULTS: The mean scoliosis improved from 72.3 degrees  to 34.9
      degrees  after initial surgery and was 35.2 degrees  at the last follow-up or
      after final fusion. T1-S1 length increased from 25.42 to 29.03 cm after initial
      surgery and to 33.32 cm at last follow-up or after final fusion with an average
      T1-S1 length increase of 1.49 cm per year. The space available for lung ratio in
      patients with thoracic curves improved from 0.84 to 0.96 at the latest follow-up.
      Three patients reached final fusion. Complications occurred in 7 of the 30
      patients, and they had a total of 13 complications. CONCLUSION: The dual GR
      technique is safe and effective in the treatment of selected cases of long,
      complex CS. It maintains correction achieved at initial surgery while allowing
      spinal growth to continue. And it has an acceptable rate of complications. The
      osteotomy at the apex vertebra with short segmental fusion of the severe rigid
      scoliosis or the patients with kyphosis could help to improve the correction and
      decrease the implant failures, with little influence on the length of the spine.

PMID- 22990367
TI  - Massive vertebral destruction associated with chronic rupture of infrarenal
      aortic aneurysm: case report and systematic review of the literature in the
      English language.
AB  - STUDY DESIGN: Case report and review of literature. OBJECTIVE: To highlight the
      specific features of a rare, life-threatening, clinical picture. SUMMARY OF
      BACKGROUND DATA: Vertebral erosion (VE) is rarely associated with contained
      rupture of an abdominal aortic aneurysm. The involvement of radicular nerves can
      mimic a discus hernia syndrome; eventually vertebral erosion induces isolated
      lower back pain. These features often lead to a delayed or wrong diagnosis of a
      life-threatening condition. Forty-two complete similar case reports have been
      published in the English literature since 1962. The most prevalent symptoms are
      low back pain and neurological signs due to compression of radicular nerves.
      METHODS: A 73-year-old man presented to Vascular Surgery department complaining
      of continuous pain in the lumbar region during the previous 6 months. The duplex
      examination revealed a huge infrarenal aortic aneurysm with an undefined
      posterior wall. Spiral CT and MR scan confirmed the aneurysm and a scalloping of
      the second and third lumbar vertebral bodies. RESULTS: A double-team
      intervention, vascular and orthopedic, consisted in aneurysm graft replacement;
      vertebral bodies excision and anterior and posterior spinal stabilization.
      Postoperatively the patient experienced reversible respiratory and renal failure
      and was discharged home in good health after 30 days. CONCLUSION: The presence of
      aortic abdominal aneurysm is always to be considered in the evaluation of an
      elderly patient complaining lower back pain or lower limb neuropathy of recent
      onset, especially in the presence of a degenerative process of the spine.

PMID- 22990368
TI  - Clay-shoveler's fracture equivalent in children.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVE: This article reports
      2 cases of clay-shoveler's fracture equivalent in children presenting acutely
      after participation in sports. SUMMARY OF BACKGROUND DATA: The clay-shoveler's
      fracture in adults is an avulsion fracture of the lower cervical or upper
      thoracic spinous process. To our knowledge, this is the first report in English
      literature on soft-tissue avulsion injury of the spinous process in children
      presenting with history and symptoms similar to clay-shoveler's fractures.
      METHODS: Retrospective review of 2 cases. RESULTS: A 14-year-old baseball player
      and a 16-year-old wrestler experienced acute posterior neck pain after
      participation in sports. Both patients presented with a history and physical
      examination suggestive of clay-shoveler's fracture but showed no evidence of
      injury on radiographs. Subsequent magnetic resonance images demonstrated an acute
      soft-tissue avulsion of the spinous process at C7 in 1 patient and T2 in the
      other. With nonoperative therapy, both patients returned to sports by 4 months,
      with occasional, intermittent discomfort a year after injury, which did not limit
      any activities. CONCLUSION: In adolescents, if the history and physical
      examination are consistent with a clay-shoveler's fracture, but radiographs are
      normal, magnetic resonance imaging may be indicated to diagnose a soft-tissue
      avulsion.

PMID- 22990370
TI  - Distal adding-on in Lenke 1A scoliosis: how to more effectively determine the
      onset of distal adding-on.
AB  - STUDY DESIGN: A radiographical follow-up and analysis. OBJECTIVE: To identify
      appropriate radiographical parameters for measuring the extent of distal adding
      on and to discuss criteria for determining the onset of distal adding-on. SUMMARY
      OF BACKGROUND DATA: There is no consensus on how to determine the onset of distal
      adding-on in Lenke 1A scoliosis. Such questions as: "Which radiographical
      parameters should be used for measuring the extent of distal adding-on?" and
      "What criteria should be applied in determining the onset of distal adding-on?"
      need to be answered. METHODS: We reviewed all the AIS cases surgically treated in
      an institution from 2003 through 2009. Inclusion criteria were as follows: (1)
      patients with Lenke 1A curves who were treated with selective thoracic fusion;
      (2) age less than 30 years; (3) 2-year radiographical follow-up. Eight
      radiographical parameters were tested to see if they are potential instruments in
      the detection of distal adding-on. RESULTS: Fifty-three patients met the
      inclusion criteria. No pseudarthrosis or crankshaft phenomenon was observed in
      the current cohort. Five out of 8 radiographical parameters: thoracic Cobb, LIV
      CSVL distance, LIV + 1-CSVL distance, thoracic AV-CSVL distance and LIV + 1 tilt
      angle, in the 2 years after surgery, showed significant increase. The remaining 3
      parameters: LIV tilt angle, T1-CSVL distance and number of vertebrae within Cobb,
      however, did not show significant increase. In regard to the 5 parameters that
      have the potential to detect the onset of distal adding-on, we found a high
      correlation between every 2 of them. The correlation coefficients range from
      0.504 to 0.962 (P = 0.001), suggesting that all of them are in a positive linear
      relationship. Regarding the criterion for determining the onset of distal adding
      on, an increase of more than 10 mm in LIV-CSVL distance in the postoperative
      period can be considered as a the main criterion because it is unlikely to be
      induced by measurement errors. CONCLUSION: LIV-CSVL distance could be an ideal
      parameter for measuring the extent of distal adding-on. Distal adding-on can be
      determined when the LIV-CSVL distance increases by 10 mm in the postoperative
      period.

PMID- 22990371
TI  - Coronary artery calcium distributions in older persons in the AGES-Reykjavik
      study.
AB  - Coronary Artery Calcium (CAC) is a sign of advanced atherosclerosis and an
      independent risk factor for cardiac events. Here, we describe CAC-distributions
      in an unselected aged population and compare modelling methods to characterize
      CAC-distribution. CAC is difficult to model because it has a skewed and zero
      inflated distribution with over-dispersion. Data are from the AGES-Reykjavik
      sample, a large population based study [2002-2006] in Iceland of 5,764 persons
      aged 66-96 years. Linear regressions using logarithmic- and Box-Cox
      transformations on CAC+1, quantile regression and a Zero-Inflated Negative
      Binomial model (ZINB) were applied. Methods were compared visually and with the
      PRESS-statistic, R(2) and number of detected associations with concurrently
      measured variables. There were pronounced differences in CAC according to sex,
      age, history of coronary events and presence of plaque in the carotid artery.
      Associations with conventional coronary artery disease (CAD) risk factors varied
      between the sexes. The ZINB model provided the best results with respect to the
      PRESS-statistic, R(2), and predicted proportion of zero scores. The ZINB model
      detected similar numbers of associations as the linear regression on ln(CAC+1)
      and usually with the same risk factors.

PMID- 22990372
TI  - A systematic literature review of risk factors for stroke in China.
AB  - Other countries have seen a decline in stroke incidence after improved treatment
      and prevention of known risk factors for stroke. China is still experiencing
      significant increases in the incidence rate of total stroke. We systematically
      reviewed the evidence on the impact of 5 modifiable risk factors (hypertension,
      dyslipidemia, obesity, diabetes, and smoking) for the risk of stroke in the
      Chinese population, with the aim to develop more effective prevention and disease
      management programs. A literature search was conducted in MEDLINE and EMBASE for
      all observational studies that reported on the association between risk of stroke
      and any of the 5 risk factors and the composite risk factor. Selected articles
      were published in either English or Chinese from January 2004 to December 2010.
      Evidence of the association between hypertension and stroke was the strongest of
      the 5 factors reported in studies, with adjusted odds ratios ranging between 2.75
      and 5.47. The association among obesity, diabetes, smoking, and the risk for
      stroke was evident, but not as strong as for hypertension. The risk ratios of
      hypertension to stroke were higher in the Chinese population than those in other
      countries.

PMID- 22990373
TI  - Energy metabolism in cardiac remodeling and heart failure.
AB  - Fatty acids are the main substrates used by mitochondria to provide myocardial
      energy under normal conditions. During heart remodeling, however, the fuel
      preference switches to glucose. In the earlier stages of cardiac remodeling,
      changes in energy metabolism are considered crucial to protect the heart from
      irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for
      glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate
      production. While myocardial function is directly associated with energy
      metabolism, the metabolic pathways could be potential targets for therapy in
      heart failure.

PMID- 22990375
TI  - Metabolic syndrome and insulin resistance comorbidity in systemic lupus
      erythematosus. Effect on carotid intima-media thickness.
AB  - OBJECTIVE: The aim of the present study was to assess the effect of metabolic
      syndrome (MetS) and insulin resistance comorbidity on the carotid intima-media
      thickness (IMT) in systemic lupus erythematosus (SLE) patients and their
      relationship to clinical manifestations, disease activity, and damage. METHODS:
      The study included 92 SLE patients (mean age 30.18 +/- 8.27 years) and 30 matched
      controls. Disease activity and damage were assessed by the SLEDAI and SLICC
      indices, respectively. The Health Assessment Questionnaire II (HAQII) and Quality
      of Life (QoL) index were evaluated in the patients. Levels of insulin, glucose,
      and creatinine and the lipid profile were measured in patients and controls.
      Insulin sensitivity was estimated using the homeostatic model assessment index
      (HOMA-B) for beta cell function and (HOMA-IR) for peripheral tissue insulin
      resistance. The carotid IMT was measured by ultrasonography. RESULTS: The SLE
      patients had high HOMA-IR and HOMA-B. The IMT was significantly increased (0.82+/
      0.29 mm) compared to the controls (0.45+/- 0.2 mm).The HOMA-IR, SLEDAI, SLICC,
      HAQII, and IMT were significantly higher and the QoL lower in those with MetS (n
      = 34) compared to those without (n = 58), while the HOMAB was comparable. There
      was a significant correlation between the IMT and the SLEDAI, SLICC, and WHR.
      CONCLUSION: Insulin sensitivity and IMT are altered in SLE patients, especially
      those with MetS comorbidity with an associated increase in disease activity and
      damage. Effective management of MetS would help control SLE activity, damage, and
      the future development of cardiovascular events especially in the absence of
      symptoms of cardiovascular disease.

PMID- 22990376
TI  - Improvement of vitamin E quality and quantity in tobacco and lettuce by
      chloroplast genetic engineering.
AB  - Vitamin E (tocopherol: Toc) is an important lipid-soluble antioxidant synthesized
      in chloroplasts. Among the 8 isoforms of vitamin E, alpha-Toc has the highest
      activity in humans. To generate transgenic plants with enhanced vitamin E
      activity, we applied a chloroplast transformation technique. Three types of the
      transplastomic tobacco plants (pTTC, pTTMT and pTTC-TMT) carrying the Toc cyclase
      (TC) or gamma-Toc methyltransferase (gamma-TMT) gene and the TC plus gamma-TMT
      genes as an operon in the plastid genome, respectively, were generated. There was
      a significant increase in total levels of Toc due to an increase in gamma-Toc in
      the pTTC plants. Compared to the wild-type plants, Toc composition was altered in
      the pTTMT plants. In the pTTC-TMT plants, total Toc levels increased and alpha
      Toc was a major Toc isoform. Furthermore, to use chloroplast transformation to
      produce alpha-Toc-rich vegetable, TC-overexpressing transplastomic lettuce plants
      (pLTC) were generated. Total Toc levels and vitamin E activity increased in the
      pLTC plants compared with the wild-type lettuce plants. These findings indicated
      that chloroplast genetic engineering is useful to improve vitamin E quality and
      quantity in plants.

PMID- 22990377
TI  - Cost of HIV and determinants of health care costs in HIV-positive patients in
      Germany: results of the DAGNA K3A Study.
AB  - OBJECTIVES: The aims of this study were to estimate the expenditure for HIV-care
      in Germany and to identify variables associated with resource use.
      DESIGN/SETTING: We performed an 18-month prospective multi-center study in an HIV
      specialized ambulatory care setting from 2006 to 2009. SUBJECTS, PARTICIPANTS:
      Patients were eligible for study participation if they (1) were HIV-positive, (2)
      were >= 18 years of age, (3) provided written consent and (4) were not enrolled
      in another clinical study; 518 patients from 17 centers were included. MAIN
      OUTCOME MEASURES: Health care costs were estimated following a micro-costing
      approach from two perspectives: (1) costs incurred to society in general, and (2)
      costs incurred to statutory health insurance. Data were obtained using
      questionnaires. Several empirical models for identifying the relationship between
      health care costs and independent variables, including age, gender, route of
      transmission and CD4 cell count at baseline, were developed. RESULTS: Average
      annual health care costs were <euro>23,298 per patient from the societal
      perspective and <euro>19,103 from the statutory health insurance perspective.
      Most expenses are caused by antiretroviral medication (80 % of the total and 89 %
      of direct costs), while hospital costs represented 7 % of total expenditure. A
      statistically significant association was found between health care costs and
      clinical variables, with higher CD4 count and female gender generating lower
      costs, while increased antiretroviral experience and injection drug use led to
      higher expenditures (P < 0.05). CONCLUSIONS: Expenditures for HIV-infection are
      driven mainly by drug costs. We identified several clinical variables influencing
      the costs of HIV-treatment. This information could assist policymakers when
      allocating limited health care resources to HIV care.

PMID- 22990379
TI  - Evaluation of motion management strategies based on required margins.
AB  - Strategies for delivering radiation to a moving lesion each require a margin to
      compensate for uncertainties in treatment. These motion margins have been
      determined here by separating the total uncertainty into components. Probability
      density functions for the individual sources of uncertainty were calculated for
      ten motion traces obtained from the literature. Motion margins required to
      compensate for the center of mass motion of the clinical treatment volume were
      found by convolving the individual sources of uncertainty. For measurements of
      position at a frequency of 33 Hz, system latency was the dominant source of
      positional uncertainty. Averaged over the ten motion traces, the motion margin
      for tracking with a latency of 200 ms was 4.6 mm. Gating with a duty cycle of 33%
      required a mean motion margin of 3.2-3.4 mm, and tracking with a latency of 100
      ms required a motion margin of 3.1 mm. Feasible reductions in the effects of the
      sources of uncertainty, for example by using a simple prediction algorithm to
      anticipate the lesion position at the end of the latency period, resulted in a
      mean motion margin of 1.7 mm for tracking with a latency of 100 ms, 2.4 mm for
      tracking with a latency of 200 ms, and 2.1-2.2 mm for the gating strategies with
      duty cycles of 33%. A crossover tracking latency of 150 ms was found, below which
      tracking strategies could take advantage of narrower motion margins than gating
      strategies. The methods described here provide a means to guide selection of a
      motion management strategy for a given patient.

PMID- 22990378
TI  - The cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid
      arthritis in Swedish clinical practice.
AB  - OBJECTIVE: The objective was to estimate the cost-effectiveness of TNF-inhibitors
      for the treatment of rheumatoid arthritis in Swedish clinical practice, both as a
      first and second biological treatment, with or without the combination of
      conventional DMARDs. Further sub-group analysis of etanercept treatment was
      performed. METHODS AND MATERIALS: Patient level data were obtained from three
      regions of the Swedish Rheumatology Registers. The dataset contained 2,558
      patients who had started TNF-inhibitor treatment, 1,049 with etanercept as their
      first biological treatment. A total of 819 patients had switched to a second TNF
      inhibitor, of which 425 to etanercept. A Markov cohort model was used in which
      health states of disease severity were classified according to HAQ and DAS28.
      Disease progression and discontinuation rates of TNF-inhibitors were based on the
      registry and for the comparator on published literature. Mortality, costs and
      utilities were based on Swedish data. The main analysis had a societal
      perspective over 20 years and efficacy was measured in quality-adjusted life
      years (QALYs). RESULTS: TNF-inhibitor treatment was associated with an increase
      in QALYs and an incremental cost compared to no biological treatment. The cost
      per QALY gained with the three TNF-inhibitors ranged from euro 50,000 to euro
      120,000, with lower estimates for TNF-inhibitors used in combination with MTX and
      as a first biologic. At a progression of 0.045 for the comparator, most values
      remain within the accepted range for cost-effectiveness. CONCLUSIONS: These
      results demonstrate that the cost per QALY for TNF-inhibitors was higher than in
      previous assessments based on registry data and that the results were sensitive
      to the HAQ progression of the comparator.

PMID- 22990380
TI  - The International Conference of Natural Product Biosynthesis (ICNPB, 8th US-Japan
      seminar on the Biosynthesis of Natural Products).

PMID- 22990382
TI  - Unusual para-substituent effects on the intramolecular hydrogen-bond in hydrazone
      based switches.
AB  - A "V"-shaped Hammett plot shows that resonance-assisted hydrogen bonding does not
      dictate the strength of the intramolecular hydrogen bond in the E isomers of
      hydrazone-based switches because it involves an aromatic pyridyl ring.

PMID- 22990381
TI  - Revisiting the enniatins: a review of their isolation, biosynthesis, structure
      determination and biological activities.
AB  - Enniatins are cyclohexadepsipeptides isolated largely from Fusarium species of
      fungi, although they have been isolated from other genera, such as Verticillium
      and Halosarpheia. They were first described over 60 years ago, and their range of
      biological activities, including antiinsectan, antifungal, antibiotic and
      cytotoxic, drives contemporary interest. To date, 29 enniatins have been isolated
      and characterized, either as a single compound or mixtures of inseparable
      homologs. Structurally, these depsipeptides are biosynthesized by a
      multifunctional enzyme, termed enniatin synthetase, and are composed of six
      residues that alternate between N-methyl amino acids and hydroxy acids. Their
      structure elucidation can be challenging, particularly for enniatins isolated as
      inseparable homologs; however, several strategies and tools have been utilized to
      solve these problems. Currently, there is one drug that has been developed from a
      mixture of enniatins, fusafungine, which is used as a topical treatment of upper
      respiratory tract infections by oral and/or nasal inhalation. Given the range of
      biological activities observed for this class of compounds, research on enniatins
      will likely continue. This review strives to digest the past studies, as well as,
      describe tools and techniques that can be utilized to overcome the challenges
      associated with the structure elucidation of mixtures of enniatin homologs.

PMID- 22990383
TI  - Towards the joint use of ICD and ICF: a call for contribution.
AB  - BACKGROUND: To optimize patient functioning, rehabilitation professionals often
      rely on measurements of functioning as well as on classifications. Although the
      International Classification of Diseases (ICD) and the International
      Classification of Functioning, Disability and Health (ICF) are used, their joint
      use has yet to become an established practice. To encourage their joint use in
      daily practice, the World Health Organization (WHO) has invited all
      rehabilitation practitioners worldwide to support the ICD-11 revision process by
      identifying the ICF categories that correspond to specific rehabilitation
      relevant health conditions. The first step in completing this task, generating
      the list of these health conditions, was taken at a February 2012 workshop in Sao
      Paulo, Brazil. OBJECTIVES: The objectives of this paper are to present the
      results of the Sao Paulo workshop, and to invite practitioners to participate in
      the ICD-ICF joint use initiative. DISCUSSION: Alternating plenary and small
      working group sessions were held and 103 rehabilitation-relevant health
      conditions were identified. With this list available, WHO together with the
      International Society of Physical and Rehabilitation Medicine (ISPRM), is
      reaching out to clinicians of all rehabilitation disciplines to take on the
      challenge of identifying the ICF categories for at least one of the health
      conditions listed.

PMID- 22990384
TI  - Percutaneous CT-guided radio-frequency ablation of osteoid osteoma of the foot
      and ankle.
AB  - INTRODUCTION: Percutaneous radiofrequency ablation (RFA) has been considered, in
      recent years, the standard treatment for osteoid osteoma (OO) of the appendicular
      skeleton. The variable clinical presentations in the foot and ankle pose problems
      in diagnosis, localization and thus treatment. The aim of this study was to
      assess the efficacy of RFA for patients with osteoid osteoma of the foot and
      ankle. MATERIALS AND METHODS: A total of 29 patients (22 males, 7 females; mean
      age 16.7 years; range 8-44 years) with OO of the foot and ankle (distal tibia, n
      = 17; distal fibula, n = 6; talus, n = 3; calcaneus, n = 3) were enrolled in the
      study. A CT-guided RFA was performed, using a cool-tip electrode without the
      cooling system, heating the lesion up to 90  degrees C for 4-5 min. Clinical
      success, assessed at a minimum follow-up of 1 year, was defined as complete or
      partial pain relief after RFA. Pain and clinical outcomes were scored pre
      operatively and at the follow-up with a visual analogue scale (VAS) and with the
      American Orthopaedic Foot and Ankle Society (AOFAS) score. Complications and
      local recurrences were also recorded. RESULTS: Clinical success was achieved in
      26 patients (89.6 %). After RFA, mean VAS and AOFAS score significantly improved
      from 8 +/- 1 to 2 +/- 1 (p < 0.05) and from 60.7 +/- 12.7 to 89.6 +/- 7.1 (p <
      0.05), respectively. Two patients experienced partial relief of pain and
      underwent a second successful ablation. Local recurrences were found in three
      patients, always associated with pain. These underwent conventional excision
      through open surgery. No early or late complications were detected after RFA.
      CONCLUSION: CT-guided RFA of foot and ankle osteoid osteoma is a safe and
      effective procedure, showing similar results for the rest of the appendicular
      skeleton.

PMID- 22990385
TI  - Screw length in the guided growth method.
AB  - BACKGROUND: The appearance of the 8-plate as a method for hemiepiphysiodesis has
      renewed the interest for the use of this technique. However, many questions
      remain unanswered about the way of action of the guided growth method. Although
      screw length has been said to play no role, to our knowledge, no clinical or
      experimental evidence exists. METHODS: An experimental prospective randomized
      study with 40 WNZ Rabbits aged 8 weeks was conducted. Four experimental groups
      were established. Each tibia was randomly allocated to one of the following
      groups: Staples (group 1), 8-plate either using self-taping screws of 9 mm (group
      2), or 5 mm lengths (groups 3) and control (group 4). Radiological assessment of
      the tibial deformity was done in a weekly fashion, and ALDA (articular line
      diaphyseal angle) variations at 6 weeks were used as the control variable.
      RESULTS: The 8-plate as a whole produced a significant bigger deformity than the
      staples (10 degrees ). No significant differences between the two models of the 8
      plate were found along the study (3.7 degrees ). CONCLUSIONS: The 8-plate has
      shown to be more efficient in producing angular deformity than staples. However,
      the length of the screw has showed no role in the 8-plate function.

PMID- 22990387
TI  - A mononuclear ruthenium complex showing multiple proton-coupled electron transfer
      toward multi-electron transfer reactions.
AB  - Two new ruthenium(II) complexes bearing dissociable protons,
      [Ru(trpy)(H(2)bim)Cl]PF(6) (1) and [Ru(trpy)(H(2)bim)(OH(2))](PF(6))(2) (2)
      (H(2)bim = 2,2'-biimidazole and trpy = 2,2':6',2''-terpyridine), were synthesized
      and characterized, where the H(2)bim and M-OH(2) moieties are expected to serve
      as proton-dissociation sites. Single crystal X-ray diffraction analyses revealed
      that the H(2)bim and M-OH(2) moieties act as proton donors in intermolecular
      hydrogen bonds. Two pK(a) values of 2 (pK(a1) = 9.0 and pK(a2) = 11.3) were
      spectrophotometrically determined, where the first proton dissociation is
      assigned to that from H(2)bim and the second is from M-OH(2). This assignment was
      supported by the density functional theory (DFT) and time-dependent density
      functional theory (TD-DFT) calculations for two sets of conjugated bases,
      [Ru(trpy)(Hbim)(OH(2))](+) and [Ru(trpy)(H(2)bim)(OH)](+) for the first proton
      dissociation, and [Ru(trpy)(Hbim)(OH)](+) and [Ru(trpy)(bim)(OH(2))](+) for the
      second dissociation. Electrochemical studies in aqueous solutions under various
      pH conditions afforded the Pourbaix diagram (potential versus pH diagram) of 2,
      where the pK(a) values found from the diagram agree well with those determined
      spectrophotometrically. It was also found that demonstrates four-step proton
      coupled electron transfer (PCET) reactions to give the four-electron oxidized
      species, [Ru(IV)(trpy)(bim)(O)](2+), without electrostatic charge buildup during
      the reactions. The multiple PCET ability of 2 would be applicable to various
      multi-electron oxidation reactions. Catalysis of electrochemical water oxidation
      was indeed evaluated in the initial attempt to demonstrate multi-electron
      oxidation reactions, revealing that the water oxidation potential for 2 is lower
      than that for other ruthenium catalysts, [Ru(trpy)(bpy)(OH(2))](2+),
      [Ru(trpy)(bpm)(OH(2))](2+) and [Ru(tmtacn)(bpy)(OH(2))](2+) (bpy = 2,2'
      bipyridine, bpm = 2,2'-bipyrimidine, and tmtacn = 1,4,7-trimethyl-1,4,7
      triazacyclononane), which are known to be active catalysts for water oxidation.

PMID- 22990386
TI  - p53 mutation alters the effect of the esophageal tumor suppressor KLF5 on
      keratinocyte proliferation.
AB  - Kruppel-like factor 5 (KLF5) is a key transcriptional regulator that is typically
      pro-proliferative in non-transformed epithelial cells but inhibits proliferation
      in transformed epithelial cells. However, the underlying mechanisms for this
      context-dependent function are not known. KLF5 is epigenetically silenced and
      exhibits a tumor suppressive function in esophageal squamous cell cancer (ESCC).
      Since p53 mutation is the most common genetic alteration in ESCC, as in other
      human epithelial cancers, we hypothesized that the context-dependent functions of
      KLF5 in cell proliferation were dependent on p53 status. In fact, in non
      transformed human primary esophageal keratinocytes, when p53 was wild-type, KLF5
      was pro-proliferative; however, KLF5 became anti-proliferative when p53 was
      mutated. KLF5 loss in human primary keratinocytes harboring p53 mutation
      accelerated the cell cycle and decreased expression of p21Waf1/Cip1; similar
      effects were also seen in ESCC cells with established p53 mutations. Further,
      p21Waf1/Cip1 was directly and differentially bound and regulated by KLF5 in the
      presence or absence of mutant p53, and suppression of p21Waf1/Cip1 reversed the
      antiproliferative effects of KLF5 in the presence of p53 mutation. Thus, KLF5 is
      a critical brake on an aberrant cell cycle, with important tumor suppressive
      functions in esophageal squamous cell and potentially other epithelial cancers.

PMID- 22990388
TI  - Contribution of novel ATGL missense mutations to the clinical phenotype of NLSD
      M: a strikingly low amount of lipase activity may preserve cardiac function.
AB  - The lack of adipose triglyceride lipase (ATGL), a patatin-like phospholipase
      domain-containing enzyme that hydrolyzes fatty acids from triacylglycerol (TAG)
      stored in multiple tissues, causes the autosomal recessive disorder neutral lipid
      storage disease with myopathy (NLSD-M). In two families of Lebanese and Italian
      origin presenting with NLSD-M, we identified two new missense mutations in highly
      conserved regions of ATGL (p.Arg221Pro and p.Asn172Lys) and a novel nonsense
      mutation (p.Trp8X). The Lebanese patients harbor homozygous p.Arg221Pro, whereas
      the Italian patients are heterozygotes for p.Asn172Lys and the p.Trp8X mutation.
      The p.Trp8X mutation results in a complete absence of ATGL protein, while the
      p.Arg221Pro and p.Asn172Lys mutations result in proteins with minimal lipolytic
      activity. Although these mutations did not affect putative catalytic residues or
      the lipid droplet (LD)-binding domain of ATGL, cytosolic LDs accumulated in
      cultured skin fibroblasts from the patients. The missense mutations might
      destabilize a random coil (p.Asn172Lys) or a helix (p.Arg221Pro) structure within
      or proximal to the patatin domain of the lipase, thereby interfering with the
      enzyme activity, while leaving intact the residues required to localize the
      protein to LDs. Overexpressing wild-type ATGL in one patient's fibroblasts
      corrected the metabolic defect and effectively reduced the number and area of
      cellular LDs. Despite the poor lipase activity in vitro, the Lebanese siblings
      have a mild myopathy and not clinically evident myocardial dysfunction. The
      patients of Italian origin show a late-onset and slowly progressive skeletal
      myopathy. These findings suggest that a small amount of correctly localized
      lipase activity preserves cardiac function in NLSD-M.

PMID- 22990390
TI  - Aerosolized lidocaine during invasive mechanical ventilation: in vitro
      characterization and clinical efficiency to prevent systemic and cerebral
      hemodynamic changes induced by endotracheal suctioning in head-injured patients.
AB  - BACKGROUND: In patients with severe brain injury, endotracheal suctioning (ETS)
      can increase intracranial pressure (ICP) and reduce cerebral perfusion pressure
      (CPP). The aim of this prospective, blinded clinical trial was to assess the
      effectiveness of aerosolized lidocaine to prevent increase of ICP induced by ETS
      in mechanically ventilated head-injured patients. METHODS: First, we measured the
      particle size of aerosolized lidocaine produced by a vibrating plate nebulizer.
      Second, we measured the cerebral hemodynamic response to tracheal suctioning in
      patients in a neurosurgical intensive care unit with and without pretreatment of
      aerosolized lidocaine. RESULTS: Particle size distribution of aerosolized
      lidocaine was suitable to reach the bronchotracheal target during mechanical
      ventilation. In 15 patients included in this study, aerosolized lidocaine by
      itself did not induce significant changes in ICP. ETS caused an increase in ICP
      (variation: 6+/-2 mm Hg, P<0.05) with a concomitant decrease in CPP (variation:
      2+/-2 mm Hg, P<0.05) that was maximal at 1 minute after NaCl aerosolization. This
      was prevented by aerosolization of lidocaine (variation of ICP: 1+/-1 mm Hg, and
      CPP: -1+/-1 mm Hg, P<0.05). CONCLUSIONS: Aerosolized lidocaine (2 mg/kg) can
      prevent ETS-induced increases in ICP, without modifying systemic and cerebral
      hemodynamics in deeply sedated patients.

PMID- 22990389
TI  - Inferring causality and functional significance of human coding DNA variants.
AB  - Sequencing technology enables the complete characterization of human genetic
      variation. Statistical genetics studies identify numerous loci linked to or
      associated with phenotypes of direct medical interest. The major remaining
      challenge is to characterize functionally significant alleles that are causally
      implicated in the genetic basis of human traits. Here, I review three sources of
      evidence for the functional significance of human DNA variants in protein-coding
      genes. These include (i) statistical genetics considerations such as co
      segregation with the phenotype, allele frequency in unaffected controls and
      recurrence; (ii) in vitro functional assays and model organism experiments; and
      (iii) computational methods for predicting the functional effect of amino acid
      substitutions. In spite of many successes of recent studies, functional
      characterization of human allelic variants remains problematic.

PMID- 22990391
TI  - Foot and hip contributions to high frontal plane knee projection angle in
      athletes: a classification and regression tree approach.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: To investigate predictors of increased
      frontal plane knee projection angle (FPKPA) in athletes. BACKGROUND: The
      underlying mechanisms that lead to increased FPKPA are likely multifactorial and
      depend on how the musculoskeletal system adapts to the possible interactions
      between its distal and proximal segments. Bivariate and linear analyses
      traditionally employed to analyze the occurrence of increased FPKPA are not
      sufficiently robust to capture complex relationships among predictors. The
      investigation of nonlinear interactions among biomechanical factors is necessary
      to further our understanding of the interdependence of lower-limb segments and
      resultant dynamic knee alignment. METHODS: The FPKPA was assessed in 101 athletes
      during a single-leg squat and in 72 athletes at the moment of landing from a
      jump. The investigated predictors were sex, hip abductor isometric torque,
      passive range of motion (ROM) of hip internal rotation (IR), and shank-forefoot
      alignment. Classification and regression trees were used to investigate nonlinear
      interactions among predictors and their influence on the occurrence of increased
      FPKPA. RESULTS: During single-leg squatting, the occurrence of high FPKPA was
      predicted by the interaction between hip abductor isometric torque and passive
      hip IR ROM. At the moment of landing, the shank-forefoot alignment, abductor
      isometric torque, and passive hip IR ROM were predictors of high FPKPA. In
      addition, the classification and regression trees established cutoff points that
      could be used in clinical practice to identify athletes who are at potential risk
      for excessive FPKPA. CONCLUSION: The models captured nonlinear interactions
      between hip abductor isometric torque, passive hip IR ROM, and shank-forefoot
      alignment.

PMID- 22990392
TI  - Photophysical properties of 3-[2-(N-phenylcarbazolyl)benzoxazol-5-yl]alanine
      derivatives--experimental and theoretical studies.
AB  - Solvatochromic probes are often used in biophysical studies to obtain information
      about polarity of the microenvironment. As there is not much natural fluorophores
      with such properties, there is still need for new synthetic compounds such as 3
      (2-benzoxazol-5-yl)alanine derivatives. Among this group of non-proteinogenic
      fluorescent amino acids especially interesting are 3-[2-(4-aminophenyl)benzoxazol
      5-yl]alanine derivatives whose solvatochromism depends on the substituents on the
      nitrogen atom, as revealed by our recent studies. To expand them we synthesized
      two new derivatives with an N-phenylcarbazole moiety in position 2 of the
      benzoxazole ring and studied their photophysical properties in solvents of
      different polarity and ability to form hydrogen bonds using absorption and steady
      state and time-resolved fluorescence spectroscopy. Applying single parameter and
      multi-linear correlations with different solvent parameters, the excited state
      dipole moments were determined as well as the influence of solvent parameters on
      each photophysical property was estimated. Moreover, the geometry of compounds
      and vertical absorption transition were theoretically calculated (DFT and TD DFT
      methods). It was found that the place of substitution of the N-phenylcarbazole
      part by the benzoxazole unit determines the character of the electron transition
      (pi-pi* or ICT) and thereby the spectral and photophysical properties of the
      compounds studied.

PMID- 22990393
TI  - To hit a moving target.

PMID- 22990394
TI  - An experimental study of prescribed walking in the management of venous leg
      ulcers.
AB  - OBJECTIVE: To determine the relationship between the level of patient activity in
      the form of walking and the rate of venous leg ulcer (VLU) healing. METHOD: Forty
      patients with newly diagnosed VLUs were recruited to the study a nd randomly
      allocated to either control or exercise groups. All patients were treated with
      multilayer compression bandaging for 12 weeks, or until their ulcer had fully
      healed. Daily stepping rate was recorded at initial assessment and following 4
      weeks of treatment. Participants in the exercise group were encouraged to
      increase their daily steps with a target of 10 000 steps per day. The control
      group were n ot asked to change their daily steps. RESULTS: In total, 33% of the
      exercise group achieved an average of 10 000 steps per day. Participants who took
      more steps at both the baseline and 4-week assessment healed more quickly than
      those who took fewer steps (p=0.052 and p=0.008 for baseline and week 4,
      respectively). Sixty-seven per cent of the participants who increased their daily
      steps had venous ulcers, which were healed by week 8, compared with 35% of those
      who did not. CONCLUSION: Participants who took more steps per day showed faster
      venous ulcer healing times when compared with those who took fewer steps,
      emphasising the benefit of walking in this patient group. Further studies are
      necessary to confirm these early findings. DECLARATION OF INTEREST: There were no
      external sources of funding for this study. The authors have no conflict of
      interest to declare.

PMID- 22990395
TI  - Review of emergency department wound management in soft tissue trauma - is there
      a plan?
AB  - OBJECTIVE: To assess current acute wound management in English emergency
      departments. METHOD: All English emergency departments including minor injury
      units (n=207) were successfully contacted and a telephone questionnaire was
      completed. This considered wound treatment policy; management including
      cleansing, analgesia, dressing selection, suturing, referral patterns, medical
      photography and antibiotic use. RESULTS: There was a 100% response. Only 40% of
      departments had a wound treatment policy. Most had implemented staff training,
      however the nature and timing of this was variable. Wound cleansing was performed
      by all departments. Most administered analgesia. Suturing was selectively
      performed by all departments. There was great diversity regarding dressing
      selection. The most common reasons for referral to specialist units were the
      complexity of injury and cosmetically sensitive areas. Photographs were regularly
      taken in one third of units questioned. CONCLUSION: This study confirmed an
      absence of a standard protocol for early soft tissue wound management in the
      emergency department setting. Key areas that could be improved are dressing
      simplification, more defined referral criteria and introduction of standardised
      protocols with structured teaching programmes. We propose a simple approach to
      management of acute soft tissue wounds that can be applied to most situations.
      DECLARATION OF INTEREST: There were no external sources of funding for this
      study. The authors have no conflicts of interest to declare.

PMID- 22990396
TI  - Regarding the Guest et al. article.

PMID- 22990397
TI  - Role of early radical debridement and skin cover in diabetic  foot ulceration.
AB  - OBJECTIVE: To assess the efficacy of radical debridement and skin grafting in
      treating diabetic foot ulceration, compared with conservative wound treatment.
      METHOD: The medical notes for 30 patients who underwent skin grafting for
      diabetic foot ulceration (graft group) were retrospectively analysed and matched,
      according to age, gender, ankle brachial pressure index (ABPI) and comorbidities,
      with 30 other patients, who were treated conservatively (control group). Patients
      in the graft group underwent early, radical debridement to prepare the wound bed
      for grafting. Graft take, rate of ulcer recurrence and donor-site morbidity were
      assessed. Healing times and the length of hospital stays were compared between
      the two groups. RESULTS: A 100% skin graft take was recorded in 80% of the
      patients on day 4, postoperatively. Ninety-three per cent of patients in the
      graft group completely healed, with 2 patients (6.7%) experiencing ulcer
      recurrence within the following 6 months. Ulcer recurrence could be due to early,
      non-guarded ambulation. Mean healing time and hospital stay were significantly
      lower in the graft group compared with the control group (4.0 +/- 1.5 weeks vs
      10.0 +/- 1.0 weeks; p < 0.001). Mean healing time in smokers was slightly greater
      than non-smokers. CONCLUSION: Skin graft is an effective method of managing
      diabetic foot ulcers compared with dressings. It reduced healing times and
      hospital stay with minimum donor-site morbidity. DECLARATION OF INTEREST: There
      were no external sources of funding for this study. The authors have no conflicts
      of interest to declare.

PMID- 22990398
TI  - An RCT to compare a bio-cellulose wound dressing with a  non-adherent dressing in
      VLUs.
AB  - OBJECTIVE: To compare the efficacy of a bio-cellulose dressing (BWD) versus a non
      adherent wound contact layer in venous leg ulcer (VLU) outpatients. METHOD: In a
      prospective, randomised, controlled multicentre study, 48 VLU patients were
      randomised to receive compression bandages and either standard care (non-adherent
      dressing; n=23) or a BWD (Suprasorb X; n=25). VLUs were evaluated for debridement
      efficacy, time to 75-100% granulation and >= 50% re-epithelialisation, reduction
      of ulcer size and patient-reported ulcer pain, comparing the status at day 0 and
      weekly, over a 12-week study treatment period. RESULTS: Thirty-three patients
      (n=18 BWD and n=15 control dressing) were included in the analysis. Autolytic
      debridement was significantly faster in the BWD group, with an 84% removal of
      yellow tissue compared with 26% in the control group, over the 12-week period (p
      < 0.0001). A median of 25 days were required to achieve 75-100% granulation in
      the BWD group vs 36 days for controls. A median of 36 days was taken to achieve
      >= 50% re-epithelialisation in the BWD group vs 50 days for controls. Patient
      reported ulcer pain reduced significantly faster in the BWD group (p < 0.05), by
      week 7, 100% of patients reported no pain, compared with 63% of controls.
      CONCLUSION: Autolytic debridement was faster and more effective in the BWD group
      compared with standard care, as was pain reduction. Although the time to healing
      was shorter with the BWD vs standard care, the difference was not statistically
      significant. DECLARATION OF INTEREST: This study was supported by Xylos
      Corporation. The study product was called X-Cell at the time, and is now
      available as Suprasorb X (Lohmann & Rauscher). Each principal investigator
      (Alvarez, Phillips, Menzoian, Etris-Brown) and respective clinical centre
      received funding for the conduct of the study. Each site executed a clinical
      study agreement independently with the sponsor. The sponsors had no role in the
      design and conduct of the study, in the collection, analysis, or interpretation
      of data, or in the preparation of the manuscript, review, or approval of the
      manuscript. None of the authors received administrative, technical or material
      support for the conduct of this study. The authors have no relevant financial
      interest in this article.

PMID- 22990399
TI  - Porcine bladder extracellular matrix for closure of a large defect in a burn
      contracture release.
AB  - Porcine bladder extracellular matrix (PBEM) is an innovative wound healing
      alternative to traditional wound closure and reconstruction. By stimulating blood
      vessel formation and chemotaxis of progenitor cells to the site of injury, it
      promotes a unique healing environment favouring regeneration of native tissue
      over scar formation. This is the first clinical report describing the novel use
      of PBEM scaffold material to close a large defect resulting from a burn
      contracture release. The benefits of this method are the improved functional and
      cosmetic result. PBEM-moderated tissue regeneration may serve a valuable role in
      burn reconstruction.

PMID- 22990400
TI  - Modulation of cutaneous wound healing by silymarin in rats.
AB  - OBJECTIVE: To investigate the effect of topical application of silymarin on full
      thickness cutaneous wounds in rats. METHOD: A full-thickness cutaneous defect
      (2*2cm) was induced on the back of 85 male and female Wister rats. The animals
      were randomly divided into four groups (n=20 in each group), treated with 1ml
      basal cream (placebo group), low-dose (6mg/ml/rat) and high-dose (12mg/ml/rat)
      silymarin, and untreated (control). Five rats remained uninjured to serve as
      comparisons for biomechanical analysis. Wounds were evaluated 10, 20 and 30 days
      after injury, through histopathologic, biochemical and biomechanical analyses.
      RESULTS: There was a significant (p < 0.05) increase observed in the amount of
      glycosaminoglycans and collagen present on days 10, 20 and 30 for both low-dose
      and high-dose silymarin groups. Low-dose silymarin reduced the number of
      lymphocytes and enhanced the number of fibrocytes at the earlier stages of wound
      healing; however, high-dose silymarin reduced both lymphocytes and macrophages,
      and increased number of fibrocytes at the later stages of wound healing.
      Silymarin significantly improved alignment of the healing tissue, enhanced
      maturity of the collagen fibres and fibroblasts (p < 0,05), and increased the
      ultimate tensile strength and stress of the healing tissue. CONCLUSION: The
      results suggest that topical application of silymarin improved the morphological,
      biochemical and biomechanical properties of experimentally-induced wound defects
      in rats. DECLARATION OF INTEREST: There were no external sources of funding for
      this study. The authors have no conflicts of interest to declare.

PMID- 22990403
TI  - Interactions between dehydrobenzo[12]annulene (DBA) and gas molecules: do the
      preorganized acetylenes work cooperatively?
AB  - Intermolecular interactions of the cyclic conjugated molecule (DBA) with
      hydrogen, nitrogen and carbon dioxide molecules were evaluated by high level ab
      initio calculations.

PMID- 22990404
TI  - Are catecholamine-derived indexes in adrenal venous sampling useful for judging
      selectivity and laterality in patients with primary aldosteronism?
AB  - In order to investigate retrospectively whether catecholamine concentrations
      obtained by adrenal venous sampling (AVS) are useful for lateralization of the
      aldosteronoma-bearing adrenal gland. The study population comprised 35 patients
      (10 men, 25 women; mean age, 49.8 years) with aldosteronoma and 18 patients (9
      men, 9 women; mean age, 51.8 years) with non-functioning adenoma who underwent
      AVS between 1994 and 2010. In all cases, AVS was performed without administering
      adrenocorticotrophic hormone. Successful or unsuccessful adrenal vein blood
      sampling (selectivity) was judged by the ratio of plasma cortisol (C) level in
      each adrenal vein to that in the infra-renal inferior vena cava [C(side)/C(IVC)]
      as a gold standard, with successful selectivity defined using four different cut
      off values [C(side)/C(IVC) >= 3.0, 2.0, 1.36 or 1.1]. Receiver operating
      characteristics (ROC) analyses were conducted to determine: (1) degree of
      selectivity; and (2) the best catecholamine (epinephrine, norepinephrine, and
      dopamine)-derived index for lateralization of the aldosteronoma-bearing adrenal
      gland. Among the catecholamine-derived indexes, the epinephrine concentration
      ratio of adrenal vein to IVC was the most reliable for all four different cut-off
      values in the evaluation of adrenal vein selectivity. Meanwhile, the ratio of
      aldosterone to norepinephrine between dominant and non-dominant sides was the
      most reliable index (right: area under the curve (AUC), 0.965 +/- 0.024; 95 %
      confidence interval (CI), 0.874-0.996; left: AUC, 0.937 +/- 0.033; 95 % CI, 0.834
      0.985) for lateralization of the aldosteronoma-bearing gland. Catecholamine
      concentrations obtained by AVS are useful for not only judging selectivity, but
      also lateralization of the aldosteronoma-bearing gland.

PMID- 22990406
TI  - Cloud point extraction-atomic absorption spectrometry for pre-concentration and
      determination of cadmium in cigarette samples.
AB  - A new complexing agent, 2-((2-((1H-benzo[d]imidazole-2yl)methoxy)phenoxy)methyl)
      1H-benzo[d]imidazole (BIMPI), was used in cloud point extraction and applied for
      selective pre-concentration of trace amounts of cadmium in cigarette samples.
      Cadmium was complexed with BIMPI in a buffer solution (pH = 10) using Triton X
      114 as surfactant and quantitatively extracted into a small volume of the
      surfactant-rich phase after centrifugation. Under optimized conditions (pH =
      10.0, 0.8 * 10(-4) mol L(-1) BIMPI and 0.08 % (w/v) Triton X-114), calibration
      graph was linear in the range of 34.0-1,670.0 MUg L(-1). The proposed method was
      applied to the determination of Cd in various cigarette (tobacco) samples which
      gave satisfactory results.

PMID- 22990405
TI  - Hormones as doping in sports.
AB  - Though we may still sing today, as did Pindar in his eighth Olympian Victory Ode,
      "... of no contest greater than Olympia, Mother of Games, gold-wreathed
      Olympia...", we must sadly admit that today, besides blatant over
      commercialization, there is no more ominous threat to the Olympic games than
      doping. Drug-use methods are steadily becoming more sophisticated and ever harder
      to detect, increasingly demanding the use of complex analytical procedures of
      biotechnology and molecular medicine. Special emphasis is thus given to anabolic
      androgenic steroids, recombinant growth hormone and erythropoietin as well as to
      gene doping, the newly developed mode of hormones abuse which, for its detection,
      necessitates high-tech methodology but also multidisciplinary individual measures
      incorporating educational and psychological methods. In this Olympic year, the
      present review offers an update on the current technologically advanced endocrine
      methods of doping while outlining the latest procedures applied-including both
      the successes and pitfalls of proteomics and metabolomics-to detect doping while
      contributing to combating this scourge.

PMID- 22990407
TI  - Temporal variability in water quality parameters--a case study of drinking water
      reservoir in Florida, USA.
AB  - Our objective was to evaluate changes in water quality parameters during 1983
      2007 in a subtropical drinking water reservoir (area: 7 km(2)) located in Lake
      Manatee Watershed (area: 338 km(2)) in Florida, USA. Most water quality
      parameters (color, turbidity, Secchi depth, pH, EC, dissolved oxygen, total
      alkalinity, cations, anions, and lead) were below the Florida potable water
      standards. Concentrations of copper exceeded the potable water standard of <30
      MUg l(-1) in about half of the samples. About 75 % of total N in lake was organic
      N (0.93 mg l(-1)) with the remainder (25 %) as inorganic N (NH3-N: 0.19, NO3-N:
      0.17 mg l(-1)), while 86 % of total P was orthophosphate. Mean total N/P was <6:1
      indicating N limitation in the lake. Mean monthly concentration of chlorophyll-a
      was much lower than the EPA water quality threshold of 20 MUg l(-1).
      Concentrations of total N showed significant increase from 1983 to 1994 and a
      decrease from 1997 to 2007. Total P showed significant increase during 1983-2007.
      Mean concentrations of total N (n = 215; 1.24 mg l(-1)) were lower, and total P
      (n = 286; 0.26 mg l(-1)) was much higher than the EPA numeric criteria of 1.27 mg
      total N l(-1) and 0.05 mg total P l(-1) for Florida's colored lakes,
      respectively. Seasonal trends were observed for many water quality parameters
      where concentrations were typically elevated during wet months (June-September).
      Results suggest that reducing transport of organic N may be one potential option
      to protect water quality in this drinking water reservoir.

PMID- 22990409
TI  - Spontaneous stone passage: is it Ammi visnaga effect?
AB  - Ammi visnaga was used in Ancient Egypt as an herbal remedy for renal colic.
      "Khellin", a chemical obtained from Ammi visnaga, was used as a smooth muscle
      relaxant and has been thought to have pleiotropic effects on urolithiasis. We
      report a case with multiple ureteral stone passages possibly as a result of
      medication with an herb preparation, Khellin.

PMID- 22990410
TI  - What is the value of bone remodeling markers in patients with calcium stones?

PMID- 22990411
TI  - Ambient temperature and activation of implantable cardioverter defibrillators.
AB  - The degree to which weather influences the occurrence of serious cardiac
      arrhythmias is not fully understood. To investigate, we studied the timing of
      activation of implanted cardiac defibrillators (ICDs) in relation to daily
      outdoor temperatures using a fixed stratum case-crossover approach. All patients
      attending ICD clinics in London between 1995 and 2003 were recruited onto the
      study. Temperature exposure for each ICD patient was determined by linking each
      patient's postcode of residence to their nearest temperature monitoring station
      in London and the South of England. There were 5,038 activations during the study
      period. Graphical inspection of ICD activation against temperature suggested
      increased risk at lower but not higher temperatures. For every 1  degrees C
      decrease in ambient temperature, risk of ventricular arrhythmias up to 7 days
      later increased by 1.2 % (95 % CI -0.6 %, 2.9 %). In threshold models, risk of
      ventricular arrhythmias increased by 11.2 % (0.5 %, 23.1 %) for every 1 degrees 
      decrease in temperature below 2  degrees C. Patients over the age of 65 exhibited
      the highest risk. This large study suggests an inverse relationship between
      ambient outdoor temperature and risk of ventricular arrhythmias. The highest risk
      was found for patients over the age of 65. This provides evidence about a
      mechanism for some cases of low-temperature cardiac death, and suggests a
      possible strategy for reducing risk among selected cardiac patients by
      encouraging behaviour modification to minimise cold exposure. 

PMID- 22990412
TI  - C.E.R.A. maintains stable hemoglobin in Latin American patients on dialysis.
AB  - BACKGROUND: C.E.R.A. is a continuous erythropoietin receptor activator with
      characteristics that permit a once-monthly schedule of administration for the
      maintenance treatment for chronic kidney disease (CKD) patients. The main
      objective of this study was to assess the maintenance of Hb concentration with
      once-monthly intravenous and/or subcutaneous C.E.R.A. therapy in Latin American
      dialysis patients with chronic renal anemia previously treated with epoetin alfa
      s.c or i.v 1-3 times per week. METHODS: This was a single-arm, open-label,
      multicenter, 32-week study of anemic patients with CKD previously treated with
      epoetin alfa sc or iv 1-3 times per week. After a 4-week screening period, during
      which mean Hb levels were maintained between 10.5 and 12.5 g/dL on their previous
      erythropoiesis stimulating agent, eligible patients entered a 16-week C.E.R.A.
      dose titration period followed by a 4-week efficacy evaluation period (EEP) and a
      28-week safety follow-up. The starting dose of C.E.R.A. was based on the previous
      dose of epoetin alfa. Doses of C.E.R.A. were then adjusted to maintain Hb levels
      within +/-1.0 g/dL of the reference concentration and between 10.5 and 12.5 g/dL.
      The Hb reference concentration was defined as the mean of all Hb levels during
      screening. The primary end point was the proportion of patients maintaining a
      mean Hb concentration (g/dL) within +/-1 g/dL of their reference Hb and between
      10.5 and 12.5 g/dL during the EEP. RESULTS: A total of 163 patients from 27
      centers in Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Uruguay,
      and Venezuela entered the treatment period and 102 completed the prescribed
      course of C.E.R.A. Forty-five patients (43.7 %) maintained a mean Hb
      concentration within +/-1 g/dL of their reference Hb value and between 10.5 and
      12.5 g/dL during the EEP. The median monthly dose remained constant at 120 MUg
      during the titration period and during the EEP. On the average, there were only
      2.3 dose changes per patient in 28 weeks of treatment, covering 7 C.E.R.A.
      scheduled administrations. 53 % of all dose changes were dose decreases, 47 %
      increases. A total of 10 AEs and 4 SAEs were considered to be related to the
      study treatment. CONCLUSIONS: Once-monthly C.E.R.A. treatment effectively
      maintains stable Hb concentrations in patients with chronic renal anemia
      undergoing dialysis with a good safety and tolerability profile.

PMID- 22990413
TI  - A case of severe osteomalacia secondary to phosphate diabetes in a renal
      transplant recipient.
AB  - Transient hypophosphatemia is frequently observed during the first months after
      renal transplantation and is usually asymptomatic. Phosphate diabetes is defined
      as inadequate tubular phosphorus reabsorption leading to persistent renal
      phosphorus wasting, which is an important but overlooked cause of osteodystrophy
      in the post-renal transplantation population. We report the case of a 58-year-old
      male who presented with severe multiple osteoarticular pains within 3 months
      after successful first kidney transplantation. Bone disease was attributed
      initially to mild hyperparathyroidism secondary to vitamin D deficiency. Despite
      the correction of the hyperparathyroidism, the withdrawal of corticosteroids, and
      the reduction of immunosuppressive treatment to tacrolimus-based monotherapy, the
      osteoarticular pains persisted. Skeletal investigations at month 9 post
      transplantation demonstrated a significant bone mineral density loss associated
      with osteomalacia and osteoporosis on the bone biopsy. Laboratory data showed
      persistent hypophosphatemia, and phosphate diabetes was then diagnosed explaining
      the post-transplant bone disease. A tacrolimus-induced renal tubular disorder was
      suspected to contribute to the excessive renal phosphorus wasting. The
      replacement of tacrolimus by sirolimus, in addition to oral phosphorus and
      vitamin D supplementations, led to the disappearance of pains, the normalization
      of urinary and plasma phosphate level, and a significant improvement of bone
      mineralization.

PMID- 22990414
TI  - Effectiveness of everolimus-eluting stents in the treatment of drug-eluting stent
      versus bare-metal stent restenosis.
AB  - BACKGROUND: The efficacy of drug-eluting stents (DES) for the treatment of in
      stent restenosis (ISR) after DES implantation is not well defined. This study
      compared the clinical outcome after the use of everolimus-eluting stents (EES)
      for the treatment of bare-metal stent (BMS) versus DES restenosis. METHOD: Ninety
      four patients with 94 ISR were included in this study. Sixty-four patients had
      BMS-ISR and 30 patients had DES-ISR. Patients were treated by repeat PCI using an
      EES. The primary endpoint of the study was survival free of target lesion
      revascularization (TLR) at 12 months or DES-ISR versus BMS-ISR patients. The
      secondary endpoints were survival free of major adverse cardiac events (MACE) and
      definite stent thrombosis. RESULTS: The baseline clinical and angiographic
      parameters were comparable between the two groups. Treatment of DES-ISR was
      associated with higher rates of recurrent TLR, myocardial infarction (MI), and
      MACE at the 12-month follow-up compared with the treatment of BMS-ISR (23.3
      versus 1.6%, P=0.002 for TLR; 13.3 versus 0%, P=0.017 for MI; and 30 versus 4.6%,
      P=0.003 for MACE). There were no differences in mortality and definite stent
      thrombosis between both groups (P=0.5686 and 0.6927, respectively). Initial stent
      number (odds ratio=1.13, 95% confidence interval 1.02-1.25; P=0.024) and initial
      stent type being a DES (odds ratio=8.11, 95% confidence interval 5.99-10.45;
      P<0.001) were independent predictors of recurrent TLR after the treatment of ISR
      using an EES. CONCLUSION: EES used for the treatment of DES-ISR is associated
      with higher rates of recurrent revascularization, MI, and MACE compared with EES
      for the treatment of BMS-ISR.

PMID- 22990415
TI  - Prognosis of different types of atrial fibrillation in the primary angioplasty
      era.
AB  - BACKGROUND: Atrial fibrillation (AF) has been associated with a poor prognosis in
      patients with ST-segment elevation myocardial infarction. There is considerable
      controversy regarding the prognostic implications of different types of AF.
      METHODS AND RESULTS: We analyzed 913 patients consecutively admitted to our
      center with ST-segment elevation myocardial infarction undergoing a primary
      percutaneous coronary intervention. Clinical, ECG, and angiographic data were
      collected. We carried out univariate and multivariate analysis, using a combined
      endpoint of death, reinfarction, stroke, and clinically relevant bleeding. AF was
      documented in 117 patients. Among them, 25 presented AF at admission (previous
      AF) and 92 developed new-onset AF (66% transient, 13% persistent). Patients with
      AF were older, more frequently men, and had a worse Killip class, and a poorer
      left-ventricular ejection fraction. When analyzing the different types of AF,
      patients with new-onset AF (persistent and transient) had a higher Killip class
      and a worse left-ventricular ejection fraction. AF was associated with
      significantly higher in-hospital mortality and with a greater incidence of in
      hospital adverse events. An increase in in-hospital mortality was recorded both
      for previous and for new-persistent AF, but after adjusting for confounding
      factors, only persistent AF was found to carry a worse short-term prognosis.
      CONCLUSION: In patients undergoing primary angioplasty in the stent era, AF is
      associated with a poor prognosis. This risk appears to be particularly high among
      patients with persistent AF.

PMID- 22990416
TI  - In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic
      resonance.
AB  - The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the
      regulation of brain energy regulation and metabolism, yet brain TCA cycle
      intermediates have never been directly detected in vivo. This study reports the
      first direct in vivo observation of a TCA cycle intermediate in intact brain,
      namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal
      activity. Our observation reveals important information about in vivo biochemical
      processes hitherto considered undetectable. In particular, it provides direct
      evidence that transport across the inner mitochondria membrane is rate limiting
      in the brain. The hyperpolarized magnetic resonance protocol designed for this
      study opens the way to direct and real-time studies of TCA cycle kinetics.

PMID- 22990417
TI  - Stroke induces long-lasting deficits in the temporal fidelity of sensory
      processing in the somatosensory cortex.
AB  - Recovery from stroke is rarely complete as humans and experimental animals
      typically show lingering deficits in sensory function. One explanation for
      limited recovery could be that rewired cortical networks do not process sensory
      stimuli with the same temporal precision as they normally would. To examine how
      well peri-infarct and more distant cortical networks process successive vibro
      tactile stimulations of the affected forepaw (a measure of temporal fidelity), we
      imaged cortical depolarizations with millisecond temporal resolution using
      voltage-sensitive dyes. In control mice, paired forepaw stimulations (ranging
      from 50 to 200 milliseconds apart) induced temporally distinct depolarizations in
      primary forelimb somatosensory (FLS1) cortex, and to a lesser extent in secondary
      FLS (FLS2) cortex. For mice imaged 3 months after stroke, the first forepaw
      stimulus reliably evoked a strong depolarization in the surviving region of FLS1
      and FLS2 cortex. However, depolarizations to subsequent forepaw stimuli were
      significantly reduced or completely absent (for stimuli <=100 milliseconds apart)
      in the FLS1 cortex, whereas FLS2 responses were relatively unaffected. Our data
      reveal that stroke induces long-lasting impairments in how well the rewired FLS1
      cortex processes temporal aspects of sensory stimuli. Future therapies directed
      at enhancing the temporal fidelity of cortical circuits may be necessary for
      achieving full recovery of sensory functions.

PMID- 22990418
TI  - Combined arterial spin labeling and diffusion-weighted imaging for noninvasive
      estimation of capillary volume fraction and permeability-surface product in the
      human brain.
AB  - A number of two-compartment models have been developed for the analysis of
      arterial spin labeling (ASL) data, from which both cerebral blood flow (CBF) and
      capillary permeability-surface product (PS) can be estimated. To derive values of
      PS, the volume fraction of the ASL signal arising from the intravascular space
      (v(bw)) must be known a priori. We examined the use of diffusion-weighted imaging
      (DWI) and subsequent analysis using the intravoxel incoherent motion model to
      determine v(bw) in the human brain. These data were then used in a two
      compartment ASL model to estimate PS. Imaging was performed in 10 healthy adult
      subjects, and repeated in five subjects to test reproducibility. In gray matter
      (excluding large arteries), mean voxel-wise v(bw) was 2.3+/-0.2 mL blood/100 g
      tissue (all subjects mean+/-s.d.), and CBF and PS were 44+/-5 and 108+/-2 mL per
      100 g per minute, respectively. After spatial smoothing using a 6-mm full width
      at half maximum Gaussian kernel, the coefficient of repeatability of CBF, v(bw)
      and PS were 8 mL per 100 g per minute, 0.4 mL blood/100 g tissue, and 13 mL per
      100 g per minute, respectively. Our results show that the combined use of ASL and
      DWI can provide a new, noninvasive methodology for estimating v(bw) and PS
      directly, with reproducibility that is sufficient for clinical use.

PMID- 22990419
TI  - Structural influences on the exchange coupling and zero-field splitting in the
      single-molecule magnet [Mn(III)6Mn(III)]3+.
AB  - A comprehensive synthetic, structural, mass spectrometrical, FT-IR and UV/Vis
      spectroscopic, electrochemical, and magnetic study on [Mn(III)(6)Mn(III)](3+) (=
      [{(talen(t-Bu(2)))Mn(III)(3)}(2){Mn(III)(CN)(6)}](3+)) is presented. The high
      stability of [Mn(III)(6)Mn(III)](3+) in solution allows the preparation of
      different salts and solvates: [Mn(III)(6)Mn(III)](BPh(4))(3).3MeOH.3MeCN.3Et(2)O
      (), [Mn(III)(6)Mn(III)(MeOH)(4)](BPh(4))(3).5MeOH (),
      [Mn(III)(6)Mn(III)(MeOH)(6)](BF(4))(3).9MeOH (),
      [Mn(III)(6)Mn(III)(MeOH)(6)](PF(6))(2)(OAc).11MeOH (), and
      [Mn(III)(6)Mn(III)(MeOH)(6)](lactate)(3).5MeOH.10H(2)O (). The molecular
      structure of [Mn(III)(6)Mn(III)](3+) is closely related to the already published
      [Mn(III)(6)M(c)](3+) complexes (M(c) = Cr(III), Fe(III), Co(III)). ESI mass
      spectra exhibit the signal of the [{(talen(t
      Bu(2)))Mn(III)(3)}(2){Mn(III)(CN)(6)}](3+) trication. FT-IR spectra show the
      characteristic bands of the triplesalen ligand in [Mn(III)(6)M(c)](3+) and the
      symmetric nu(C=N) vibration of the [Mn(III)(CN)(6)](3-) unit at 2135 cm(-1).
      UV/Vis spectra are dominated by intense transitions of the trinuclear Mn(III)(3)
      triplesalen subunits above 20,000 cm(-1). The electrochemical studies establish
      the occurrence of ligand-centered oxidations at ~1.0 V vs. Fc(+)/Fc, an oxidation
      of the central Mn(III) at 0.78 V, and a series of reductions of the terminal
      Mn(III) ions between -0.6 and -1.2 V. AC magnetic measurements indicate single
      molecule magnet (SMM) behavior for all compounds. The DC magnetic data are
      analyzed by a full-matrix diagonalization of the appropriate spin-Hamiltonian
      including isotropic exchange, zero-field splitting with full consideration of the
      relative orientation of the D-tensors, and Zeeman interaction, taking into
      account the diamagnetic nature of the central Mn(III) at low temperatures as
      inferred from a previous ab initio study. The spin-Hamiltonian simulations
      indicate Mn(III)-Mn(III) interactions in the -0.37 to -0.70 cm(-1) range within
      the trinuclear triplesalen subunits and in the -0.02 to +0.23 cm(-1) range across
      the central Mn(III) ion, while D(Mn) = -3.1 to -5.0 cm(-1). The differences in
      the exchange parameters and the relaxation behavior of the
      [Mn(III)(6)Mn(III)](3+) compounds are rationalized in terms of subtle variations
      in the molecular structures, especially regarding the distortion of the central
      [Mn(III)(CN)(6)](3-) core and the ligand folding. In comparison with the other
      [Mn(III)(6)M(c)](3+) compounds, this allows us to establish some general
      magnetostructural correlations for this class of complexes.

PMID- 22990420
TI  - Enhanced performance of NaTaO3 using molecular co-catalyst [Mo3S4]4+ for water
      splitting into H2 and O2.
AB  - Photocatalytic activity of NaTaO(3) was significantly improved by using a
      molecular co-catalyst [Mo(3)S(4)](4+). Its hydrogen production rate is 28 times
      higher than pure NaTaO(3). This study presents the potential of bioinspired
      molecular metal clusters as efficient co-catalysts.

PMID- 22990421
TI  - Nursing ethics perspectives on end-of-life care.

PMID- 22990422
TI  - Citations for the Human Rights and Nursing Awards 2011.

PMID- 22990423
TI  - Defining end-of-life care from perspectives of nursing ethics.
AB  - Despite increasing interests and urgent needs for quality end-of-life care, there
      is no exact definition of what is the interval referred to as end of life or what
      end-of-life care is. The purpose of this article is to report our examination of
      terms related to end-of-life care and define end-of-life care from nursing ethics
      perspectives. Current terms related to end-of-life care, such as terminal care,
      hospice care, and palliative care, are based on a medical model and are
      restrictive in terms of diagnosis and prognosis. Using codes of ethics for nurses
      as a framework, we attempt to identify people to whom nurses are responsible to
      provide end-of-life care and develop a definition of end-of-life care that is
      more inclusive and applicable to a broader range of people who would benefit from
      end-of-life care by nurses and other health-care providers.

PMID- 22990424
TI  - 'Ambivalence' at the end of life: how to understand patients' wishes ethically.
AB  - Health-care professionals in end-of-life care are frequently confronted with
      patients who seem to be 'ambivalent' about treatment decisions, especially if
      they express a wish to die. This article investigates this phenomenon by
      analysing two case stories based on narrative interviews with two patients and
      their caregivers. First, we argue that a respectful approach to patients requires
      acknowledging that coexistence of opposing wishes can be part of authentic, multi
      layered experiences and moral understandings at the end of life. Second,
      caregivers need to understand when contradictory statements point to tensions in
      a patient's moral experience that require support. Third, caregivers should be
      careful not to negatively label or even pathologize seemingly contradictory
      patient statements.

PMID- 22990425
TI  - Exploring families' experiences of an organ donation request after brain death.
AB  - This qualitative research study with a content analysis approach aimed to explore
      families' experiences of an organ donation request after brain death. Data were
      collected through 38 unstructured and in-depth interviews with 14 consenting
      families and 12 who declined to donate organs. A purposeful sampling process
      began in October 2009 and ended in October 2010. Data analysis reached 10
      categories and two major themes were listed as: (1) serenity in eternal freedom;
      and (2) resentful grief. The central themes were peace and honor versus doubt and
      regret. The findings indicated that the families faced with an organ donation
      request of a brain-dead loved one experienced a lasting effect long after the
      patient's demise regardless of their decision to donate or refusal to donate. In
      conclusion, this study highlights the importance of family support and follow-up
      in an efficient healthcare system aimed at developing trust with the families and
      providing comfort during and after the final decision.

PMID- 22990426
TI  - Intensive care nurses' involvement in the end-of-life process--perspectives of
      relatives.
AB  - In this article, we report findings from a qualitative study that explored how
      the relatives of intensive care unit patients experienced the nurses' role and
      relationship with them in the end-of-life decision-making processes. In all, 27
      relatives of 21 deceased patients were interviewed about their experiences in
      this challenging ethical issue. The findings reveal that despite bedside
      experiences of care, compassion and comfort, the nurses were perceived as vague
      and evasive in their communication, and the relatives missed a long-term
      perspective in the dialogue. Few experienced that nurses participated in meetings
      with doctors and relatives. The ethical consequences imply increased loneliness
      and uncertainty, and the experience that the relatives themselves have the
      responsibility of obtaining information and understanding their role in the
      decision-making process. The relatives therefore felt that the nurses could have
      been more involved in the process.

PMID- 22990427
TI  - Euthanasia and physician-assisted suicide: knowledge, attitudes and experiences
      of nurses in Andalusia (Spain).
AB  - The aim of this study is to assess the knowledge, attitudes and experiences of
      Spanish nurses in relation to euthanasia and physician-assisted suicide. In an
      online questionnaire completed by 390 nurses from Andalusia, 59.1% adequately
      identified a euthanasia situation and 64.1% a situation involving physician
      assisted suicide. Around 69% were aware that both practices were illegal in
      Spain, while 21.4% had received requests for euthanasia and a further 7.8% for
      assisted suicide. A total of 22.6% believed that cases of euthanasia had occurred
      in Spain and 11.4% believed the same for assisted suicide. There was greater
      support (70%) for legalisation of euthanasia than for assisted suicide (65%),
      combined with a greater predisposition towards carrying out euthanasia (54%), if
      it were to be legalised, than participating in assisted suicide (47.3%). Nurses
      in Andalusia should be offered more education about issues pertaining to the end
      of life, and extensive research into this area should be undertaken.

PMID- 22990428
TI  - Flemish palliative-care nurses' attitudes to palliative sedation: a quantitative
      study.
AB  - Palliative sedation is an option of last resort to control refractory suffering.
      In order to better understand palliative-care nurses' attitudes to palliative
      sedation, an anonymous questionnaire was sent to all nurses (589) employed in
      palliative care in Flanders (Belgium). In all, 70.5% of the nurses (n = 415)
      responded. A large majority did not agree that euthanasia is preferable to
      palliative sedation, were against non-voluntary euthanasia in the case of a
      deeply and continuously sedated patient and considered it generally better not to
      administer artificial floods or fluids to such a patient. Two clusters were
      found: 58.5% belonged to the cluster of advocates of deep and continuous sedation
      and 41.5% belonged to the cluster of nurses restricting the application of deep
      and continuous sedation. These differences notwithstanding, overall the attitudes
      of the nurses are in accordance with the practice and policy of palliative
      sedation in Flemish palliative-care units.

PMID- 22990430
TI  - Levosulpiride-induced rabbit syndrome.

PMID- 22990429
TI  - Phylogeography and genetic diversity of East Asian Neolitsea sericea (Lauraceae)
      based on variations in chloroplast DNA sequences.
AB  - Neolitsea sericea is an evergreen broad leaved tree in the warm-temperate regions
      of East Asia. This area is a hotspot for plant species richness and endemism
      caused by dynamic changes in land configuration during the Quaternary. However,
      the historical migration of such evergreen tree species is still poorly
      understood. In an attempt to reconstruct the phylogeographic history of N.
      sericea during the Quaternary, we identified the chloroplast DNA haplotypes of
      287 individuals from 33 populations covering almost all of its geographic range.
      Analyses were based on sequence data from the trnL-F, psbC-trnS, and rps16
      regions. Nine haplotypes were identified. The majority included ancestral types
      in the southwestern part of the main islands of Japan, with other region-specific
      haplotypes being found in populations on the Korean Peninsula, Taiwan (Isl.
      Lanyu), and elsewhere in Japan. A statistical parsimony network revealed two
      lineages derived from Japanese main islands. One was represented on the Korean
      Peninsula, the other on Isl. Lanyu. The current distribution of N. sericea has
      been shaped by colonization via land bridges. During the glacial periods, two
      primary, but separate migration routes were followed--from the southwestern part
      of the Japanese main islands to either the Korean Peninsula or Taiwan. In
      addition, we believe the Zhoushan populations were shaped by post-glacial
      processes through an ECS land bridge (East China Sea basin) from northern refugia
      that existed during the late Pleistocene.

PMID- 22990431
TI  - Aripiprazole induced tardive dyskinesia--accruing evidence.

PMID- 22990432
TI  - Stimulant use disorders: characteristics and comorbidity in an Australian
      population sample.
AB  - OBJECTIVE: To describe the correlates of stimulant use disorders (abuse,
      dependence) in an Australian population sample, to compare the characteristics of
      stimulant users with and without stimulant use disorders and to describe the
      patterns of service use and help-seeking in people with stimulant use disorders.
      METHODS: Data were drawn from the 2007 National Survey of Mental Health and
      Wellbeing, which sampled 8841 residents of private dwellings in Australia in
      2007. Lifetime DSM-IV substance use and mental disorder diagnoses were obtained
      from interviews conducted by lay interviewers, using the Composite International
      Diagnostic Interview (CIDI). Socio-demographic, socio-economic and clinical
      correlates of stimulant use disorders were identified using binary logistic
      regression models. Stimulant users with and without stimulant use disorders were
      compared to non-stimulant users via multinomial logistic regression models.
      RESULTS: Compared to Australians without stimulant use disorder, people with
      stimulant use disorders were younger, more likely to be male, of non-heterosexual
      orientation and born in Australia, but were not more socially disadvantaged.
      Lifetime comorbidity rates were high: 79% of persons with stimulant use disorders
      had a lifetime alcohol use disorder, 73% a lifetime cannabis use disorder, and
      more than one third a lifetime mood or anxiety disorder. Stimulant use disorders
      were associated with a family history of substance use, affective disorders and
      psychosis. One in five people with lifetime stimulant use disorders had been
      imprisoned, homeless or hospitalised for substance or mental health problems, and
      13% reported at least one symptom of psychosis. Nearly half had sought help for
      substance or mental health problems, primarily from General Practitioners (GPs),
      psychologists or psychiatrists. CONCLUSIONS: Stimulant use disorders in a
      representative population sample are associated with significant comorbidity and
      harm. Many persons with stimulant use disorders had sought care and found this
      helpful. There is scope for screening and intervention in this group.

PMID- 22990434
TI  - The absence of depressive symptoms is not the presence of wellness: validation of
      the Clinical Positive Affect Scale.
AB  - OBJECTIVE: Many patients with depression respond or remit with current
      treatments, but often experience persistent distress, in part because they
      perceive that they have not returned to their normal or premorbid state. Some
      continue to have a lack of subjective psychological well-being and positive
      affect following treatment. It would be useful to measure these deficits and
      explore whether interventions can improve them. Currently, no clinically useful
      scale has been developed to measure positive affect. To fill this gap, we
      developed the Clinical Positive Affect Scale (CPAS). METHOD: The purpose of this
      study is to describe the development and validation of the CPAS, a 16-item self
      report measurement of self-perceived affective and cognitive correlates of
      positive affect, in a sample of 300 college students. RESULTS: A principal
      component analysis with varimax rotation showed one major factor of positive
      affect, with all items revealing high loadings (>= 0.65) on the single factor.
      The CPAS also demonstrated good internal consistency (alpha = 0.97) and strong
      part-whole correlations. Finally, the CPAS revealed some degree of divergent
      validity through moderately strong negative correlations with validated measures
      of depression, anxiety and drug abuse. CONCLUSIONS: This study supports the
      validity of the CPAS, which may help clinicians and researchers to assess
      patients' current self-perceived levels of hedonic capacity and enthusiasm for
      life.

PMID- 22990437
TI  - Results of medial open reduction of developmental dysplasia of the hip with
      regard to walking age.
AB  - This study aimed to evaluate the outcome of medial open reduction for
      developmental dysplasia of the hip (DDH) in patients before and after walking
      age. A minimum 5-year radiographic and clinical follow-up compared 29 patients
      (group 1) before walking age with 38 patients (group 2) after walking age for
      DDH. The correction ratio of acetabular index was similar in both groups
      postoperatively (41.8% for group 1 and 44.9% for group 2), and it was
      statistically not significant (P>0.05). The Kalamchi-MacEwen classification
      showed no correlation between operative age and the rate of avascular necrosis
      (P>0.05). This report presents similar complication rates as that of the Severin
      criteria for medial open reduction of the hip and challenges the conventional
      belief that a medial open reduction for the treatment of DDH in a walking-age
      child at short-term to mid-term follow-up has comparable results.

PMID- 22990433
TI  - Differential putaminal morphology in Huntington's disease, frontotemporal
      dementia and Alzheimer's disease.
AB  - OBJECTIVE: Direct neuronal loss or deafferentation of the putamen, a critical hub
      in corticostriatal circuits, may result in diverse and distinct cognitive and
      motoric dysfunction in neurodegenerative disease. Differential putaminal
      morphology, as a quantitative measure of corticostriatal integrity, may thus be
      evident in Huntington's disease (HD), Alzheimer's disease (AD) and frontotemporal
      dementia (FTD), diseases with differential clinical dysfunction. METHODS: HD (n =
      17), FTD (n = 33) and AD (n = 13) patients were diagnosed according to
      international consensus criteria and, with healthy controls (n = 17), were
      scanned on the same MRI scanner. Patients underwent brief cognitive testing using
      the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Ten MRI scans from
      this dataset were manually segmented as a training set for the Adaboost
      algorithm, which automatically segmented all remaining scans for the putamen,
      yielding the following subset of the data: 9 left and 12 right putamen
      segmentations for AD; 25 left and 26 right putamina for FTD; 16 left and 15 right
      putamina for HD; 12 left and 12 right putamina for controls. Shape analysis was
      performed at each point on the surface of each structure using a multiple
      regression controlling for age and sex to compare radial distance across
      diagnostic groups. RESULTS: Age, but not sex and intracranial volume (ICV), were
      significantly different in the segmentation subgroups by diagnosis. The AD group
      showed significantly poorer performance on cognitive testing than FTD. Mean
      putaminal volumes were HD < FTD < AD <= controls, controlling for age and ICV.
      The greatest putaminal shape deflation was evident in HD, followed by FTD, in
      regions corresponding to the interconnections to motoric cortex. CONCLUSIONS:
      Differential patterns of putaminal atrophy in HD, FTD and AD, with relevance to
      corticostriatal circuits, suggest the putamen may be a suitable clinical
      biomarker in neurodegenerative disease.

PMID- 22990438
TI  - Potocki-Lupski syndrome with teratologic dislocation of the hip:  a case report.
AB  - Potocki-Lupski syndrome results from the duplication of chromosome 17 band p11.2.
      This is the first report of a case of Potocki-Lupski syndrome with teratologic
      dislocation of both hips. The diagnosis was made by chromosomal analysis. The
      association between Potocki-Lupski syndrome and musculoskeletal disorders may
      help elucidate the etiology and prognosis of the syndrome.

PMID- 22990439
TI  - Results of surgical resection in pediatric pelvic tumors.
AB  - Thirty nonmetastatic patients with malignant tumors of the pelvis underwent
      surgical resection between November 2000 and December 2009. The diagnosis
      included Ewing's sarcoma (22), osteogenic sarcoma (four), chondrosarcoma (two),
      and synovial sarcoma (two). Eighteen resections included the acetabulum and 12
      did not. Twenty-seven patients were available for follow-up. Follow-up ranged
      from 4 to 138 months (mean 43 months). Nineteen patients are currently alive.
      There were two local recurrences. The overall survival was 68% at 5 years. The
      Musculoskeletal Tumor Society Score ranged from 22 to 29. Surgery provides good
      local control and oncologic outcomes with acceptable function in these patients.

PMID- 22990440
TI  - Percutaneous pelvic osteotomy and intertrochanteric varus shortening osteotomy in
      nonambulatory GMFCS level IV and V cerebral palsy patients:  preliminary report
      on 30 operated hips.
AB  - This study evaluated the outcome of severe cerebral palsy patients (Gross Motor
      Function Classification System level IV and V) treated by simultaneous
      percutaneous pelvic osteotomy and intertrochanteric varus shortening osteotomy
      for hip subluxation or dislocation between 2002 and 2011. Twenty-four patients
      (30 hips) with an average age of 9.4 years (5-16.5) were reviewed at a mean
      follow-up of 35.9 months (6-96). Percutaneous pelvic osteotomy lasted on average
      30 min/patient per side (25-40) and was always performed through a skin incision
      of 2-3 cm. The migration percentage and acetabular angle were assessed on plain
      radiographs. The mean Reimers' migration percentage improved from 67.1% (42-100)
      preoperatively to 7.7% (0-70) at the last follow-up and the mean acetabular angle
      improved from 31.8 degrees  (22-48) to 15.7 degrees  (5-27). Five patients
      presented complications: one redislocation, one bone graft dislodgement, and
      three with avascular necrosis of the femoral head. This study should be
      considered as a pilot study. These results indicate that this combined approach
      is an effective, reliable, and minimally invasive alternative method for the
      treatment of spastic dislocated hips in severe cerebral palsy patients with an
      outcome similar to standard techniques reported in the literature.

PMID- 22990441
TI  - Longitudinal overgrowth of the femur stimulated by short-leg ambulation in
      unilateral partial tibia hemimelia.
AB  - In the treatment of unilateral partial tibia hemimelia, complications from
      extensive lengthening to correct the marked shortening and recurrent failures of
      foot reconstructions do not allow limb salvage. Treatment by amputation with
      prosthetic replacement predominates. Very often, however, amputation is rejected
      by patients. A case we treated in infancy by complete reconstruction without
      lengthening walked full weight bearing on the short leg. Twelve years later, the
      ipsilateral femur manifested 6 cm overgrowth to reduce the shortening.
      Stimulation of accelerated growth in the partial tibia hemimelia limb by axial
      directed stress of short-leg ambulation is suggested by this report, and its
      implication for enduring limb salvage is discussed.

PMID- 22990442
TI  - Single shot laser flash photolysis with a fibre-coupled reference beam monitor.
AB  - In the standard nanosecond laser photolysis method for kinetic studies, a Q
      switched laser generates transient species, and absorption spectrophotometry
      provides a measure of their concentrations. The sample is placed between the
      monitoring source (a pulsed xenon arc or a flash lamp) and a monochromator, and a
      photomultiplier tube (PMT) is used for measuring the intensity of the light
      leaving the exit slit of the monochromator. With this (single-beam) arrangement,
      the laser-induced change in the absorbance of the sample, DeltaA, can be
      calculated only if the intensity of the monitoring beam remains constant during
      the time interval of interest. When this condition is not fulfilled, a second
      measurement of the PMT output is made after blocking the path of the laser beam,
      but shot-to-shot variations in the output of the monitoring source vitiate the
      analysis when DeltaA is small. To overcome this problem, double-beam versions
      were developed in the last century, but the single-beam version still enjoys
      greater popularity. With a view to making the double-beam method easily
      implementable, some simple modifications are introduced, which permit the
      conversion of an existing laser kinetic spectrometer into a double-beam variant
      (with one or two monochromators).

PMID- 22990443
TI  - Green peach aphid infestation induces Arabidopsis PHYTOALEXIN-DEFICIENT4
      expression at site of insect feeding.
AB  - The Arabidopsis thaliana PHYTOALEXIN-DEFICIENT4 (PAD4) protein, which has
      homology to lipases, is required for phloem-based resistance against the green
      peach aphid (GPA; Myzus persicae Sulzer). PAD4 modulates antibiotic and
      antixenotic defenses against GPA. PAD4 in conjunction with its interacting
      partner ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) also functions in basal
      resistance to bacterial and oomycete pathogens by promoting salicylic acid (SA)
      dependent and SA-independent defenses. By contrast, neither EDS1 nor SA is
      required for PAD4-controlled defense against GPA. Distinct molecular activities
      of PAD4 are involved in different aspects of Arabidopsis defense against GPA and
      pathogens. Histochemical analysis of plants containing a PAD4p:GUS chimera, which
      expresses the GUS reporter from the PAD4 promoter, indicated strong PAD4 promoter
      activity at the site of penetration of the vasculature by the insect stylet. GUS
      activity was also observed in non-vascular tissues of GPA-infested leaves, thus
      raising the possibility that a combination of distinct PAD4 activities in
      vascular and non-vascular tissues contribute to Arabidopsis defense against GPA.

PMID- 22990444
TI  - Intracellular localization and physiological function of a rice Ca2+-permeable
      channel OsTPC1.
AB  - Two-pore channels (TPCs) are cation channels with a voltage-sensor domain
      conserved in plants and animals. Rice OsTPC1 is predominantly localized to the
      plasma membrane (PM), and assumed to play an important role as a Ca2+-permeable
      cation channel in the regulation of cytosolic Ca2+ rise and innate immune
      responses including hypersensitive cell death and phytoalexin biosynthesis in
      cultured rice cells triggered by a fungal elicitor, xylanase from Trichoderma
      viride. In contrast, Arabidopsis AtTPC1 is localized to the vacuolar membrane
      (VM). To gain further insights into the intracellular localization of OsTPC1, we
      stably expressed OsTPC1-GFP in tobacco BY-2 cells. Confocal imaging and membrane
      fractionation revealed that, unlike in rice cells, the majority of OsTPC1-GFP
      fusion protein was targeted to the VM in tobacco BY-2 cells. Intracellular
      localization and functions of the plant TPC family is discussed.

PMID- 22990445
TI  - Modulation of the balance between stem cell proliferation and consumption by
      ERECTA-family genes.
AB  - Stem cells in the vegetative shoot apical meristem proliferate to produce more
      stem cells (self-renewal) and are simultaneously consumed to form leaf promordia.
      Therefore, to keep a stable number of stem cells, regulation of the balance
      between their proliferation and consumption is important. Recently we reported
      that stem cell population is increased in mutant plants lacking the entire ERECTA
      (ER) receptor kinase family. Here we describe that loss of function of the entire
      ER-family causes a decrease in leaf number in spite of the increase in stem cell
      population. This suggests that stem cell consumption might be decreased in the
      mutant, and this could be one of reasons why stem cell population appears to be
      increased. This situation is in sharp contrast to clv3 mutant, which also shows
      an increase in stem cell population but does not show a decrease in leaf
      production. We briefly discuss differences between the er-family mutant and the
      clv3 mutant.

PMID- 22990446
TI  - Induction of ARI12 upon broad band UV-B radiation is suppressed by UVR8 and
      cryptochromes.
AB  - ARI12 belongs to a family of 16 potential E3 ligases in Arabidopsis and is
      strongly induced in leaves upon low and high fluence rates (HFR) of UV-B. We have
      shown that ARI12 is a downstream target of the UV-B receptor, UVR8, and the
      transcription factors HY5 and HYH under low fluence rates. However under HFR of
      broad band UV-B ARI12 expression was still downstream of HY5 and HYH but
      increased in uvr8 mutants. To determine if other photoreceptors are responsible
      for the induction of ARI12 we quantified its expression in double mutants of the
      UV-A and blue light receptors, CRY1/2 and PHOT1/2, and the red light receptors
      PHYA/B. While the expression of ARI12 was increased in cyr1/2 it was unaffected
      in phot1/2 and phyA/B. Therefore ARI12 expression is suppressed by UVR8 and
      cryptochromes, and independent of phototropins and phytochromes A and B upon HFR
      of broad band UV-B.

PMID- 22990447
TI  - The role of carbon in fungal nutrient uptake and transport: implications for
      resource exchange in the arbuscular mycorrhizal symbiosis.
AB  - The arbuscular mycorrhizal (AM) symbiosis, which forms between plant hosts and
      ubiquitous soil fungi of the phylum Glomeromycota, plays a key role for the
      nutrient uptake of the majority of land plants, including many economically
      important crop species. AM fungi take up nutrients from the soil and exchange
      them for photosynthetically fixed carbon from the host. While our understanding
      of the exact mechanisms controlling carbon and nutrient exchange is still
      limited, we recently demonstrated that (i) carbon acts as an important trigger
      for fungal N uptake and transport, (ii) the fungus changes its strategy in
      response to an exogenous supply of carbon, and that (iii) both plants and fungi
      reciprocally reward resources to those partners providing more benefit. Here, we
      summarize recent research findings and discuss the implications of these results
      for fungal and plant control of resource exchange in the AM symbiosis.

PMID- 22990448
TI  - Boomeranging in structural defense: phytophagous insect uses cycad trichomes to
      defend against entomophagy.
AB  - Plant defensive behaviors that resist arthropod herbivory include trichome
      mediated defenses, and variation in plant trichome morphology and abundance
      provides examples of the mechanistic complexities of insect-plant interactions.
      Trichomes were removed from Cycas revoluta cataphylls on the island of Guam to
      reveal Aulacaspis yasumatsui scale infestation, and predation of the newly
      exposed insects by pre-existing Rhyzobius lophanthae beetles commenced within one
      day. The quotient of predated/total scale insects was 0.5 by day 4 and stabilized
      at that found on adjacent glabrous leaves in about one week. The trichome
      phenotype covering the C. revoluta cataphyll complex offers the invasive A.
      yasumatsui armored scale effectual enemy-free space in this system. This pest and
      predator share no known evolutionary history with C. revoluta, therefore, the
      adaptive significance of this plant behavior in natural habitat is not yet known.

PMID- 22990449
TI  - Epigenetic memory of DNAi associated with cytosine methylation and histone
      modification in fern.
AB  - Gene silencing technology, such as RNA interference (RNAi), is commonly used to
      reduce gene expression in plant cells, and exogenous double-stranded RNA (dsRNA)
      can induce gene silencing in higher plants. Previously, we showed that the
      delivery of double-stranded DNA (dsDNA) fragments, such as PCR products of an
      endogenous gene sequence, into fern (Adiantum capillus-veneris) gametophytic
      cells induces a sequence-specific gene silencing that we termed DNAi. In this
      study, we used a neochrome 1 gene (NEO1) that mediates both red light-induced
      chloroplast movement and phototropism as a model of DNAi and confirmed that the
      NEO1 function was suppressed by the repression of the NEO1 gene. Interestingly,
      the gene silencing effect by DNAi was found in the progeny. Cytosine methylation
      was detected in the NEO1-silenced lines. The DNA modifications was present in the
      transcriptional region of NEO1, but no differences between wild type and the
      silenced lines were found in the downstream region of NEO1. Our data suggest that
      the DNAi gene silencing effect that was inherited throughout the next generation
      is regulated by epigenetic modification. Furthermore, the histone deacetylase
      inhibitor, trichostatin A (TSA), recovered the expression and function of NEO1 in
      the silenced lines, suggesting that histone deacetylation is essential for the
      direct suppression of target genes by DNAi.

PMID- 22990450
TI  - The salicylic acid dependent and independent effects of NMD in plants.
AB  - In eukaryotes, nonsense-mediated mRNA decay (NMD) targets aberrant and selected
      non-aberrant mRNAs for destruction. A recent screen for mRNAs showing increased
      abundance in Arabidopsis NMD-deficient mutants revealed that most are associated
      with the salicylic acid (SA)-mediated defense pathway. mRNAs with conserved
      peptide upstream open reading frames (CpuORFs or CuORFs) are hugely
      overrepresented among the smaller class of NMD-regulated transcripts not
      associated with SA. Here we show that the common phenotypes observed in
      Arabidopsis NMD mutants are SA-dependent, whereas the upregulation of CpuORF
      containing transcripts in NMD mutants is independent of SA. We speculate that
      CpuORFs could allow the conditional targeting of mRNAs for destruction using the
      NMD pathway.

PMID- 22990451
TI  - Intracellular auxin transport in pollen: PIN8, PIN5 and PILS5.
AB  - Cellular auxin homeostasis is controlled at many levels that include auxin
      biosynthesis, auxin metabolism, and auxin transport. In addition to intercellular
      auxin transport, auxin homeostasis is modulated by auxin flow through the
      endoplasmic reticulum (ER). PIN5, a member of the auxin efflux facilitators PIN
      protein family, was the first protein to be characterized as an intracellular
      auxin transporter. We demonstrated that PIN8, the closest member of the PIN
      family to PIN5, represents another ER-residing auxin transporter. PIN8 is
      specifically expressed in the male gametophyte and is located in the ER. By
      combining genetic, physiological, cellular and biochemical data we demonstrated a
      role for PIN8 in intracellular auxin homeostasis. Although our investigation shed
      light on intracellular auxin transport in pollen, the physiological function of
      PIN8 still remains to be elucidated. Here we discuss our data taking in
      consideration other recent findings.

PMID- 22990452
TI  - Regulation of ethylene biosynthesis through protein degradation.
AB  - The function of hormones during plant growth, development and response to
      environmental stresses relies heavily upon the actions of the ubiquitin
      proteasome system (UPS), which selectively degrades numerous proteins. Synthesis
      of ethylene, a growth and stress hormone, is regulated in part by the ubiquitin
      dependent degradation of the rate-limiting enzymatic protein aminocyclopropane-1
      carboxylic acid synthase (ACS). Regulation of ACS protein stability, and
      therefore ethylene production, is mediated by non-catalytic sequences within the
      C-terminal extension of many ACS proteins. In this review we provide a brief
      overview of the E3 ligases that target ACS proteins for degradation and discuss
      how post-translational modification of the C-terminal extensions influence
      protein stability.

PMID- 22990454
TI  - Objective surveillance definitions for ventilator-associated pneumonia.
AB  - OBJECTIVES: The subjectivity and complexity of surveillance definitions for
      ventilator-associated pneumonia preclude meaningful internal or external
      benchmarking and therefore hamper quality improvement initiatives for ventilated
      patients. We explored the feasibility of creating objective surveillance
      definitions for ventilator-associated pneumonia. DESIGN: We identified clinical
      signs suitable for inclusion in objective definitions, proposed candidate
      definitions incorporating these objective signs, and then applied these
      definitions to retrospective clinical data to measure their frequencies and
      associations with adverse outcomes using multivariate regression models for cases
      and matched controls. SETTING: Medical and surgical intensive care units in eight
      U.S. hospitals (four tertiary centers, three community hospitals, and one
      Veterans Affairs institution). PATIENTS: Eight thousand seven hundred thirty-five
      consecutive episodes of mechanical ventilation for adult patients. INTERVENTIONS:
      We evaluated 32 different candidate definitions composed of different
      combinations of the following signs: three thresholds for respiratory
      deterioration defined by sustained increases in daily minimum positive end
      expiratory pressure or FIO2 after either 2 or 3 days of stable or decreasing
      ventilator settings, abnormal temperature, abnormal white blood cell count,
      purulent pulmonary secretions defined by neutrophils on Gram stain, and positive
      cultures for pathogenic organisms. MEASUREMENTS AND MAIN RESULTS: Ventilator
      associated pneumonia incidence, attributable ventilator days, hospital days, and
      hospital mortality. All candidate definitions were significantly associated with
      increased ventilator days and hospital days, but only definitions requiring
      objective evidence of respiratory deterioration were significantly associated
      with increased hospital mortality. Significant odds ratios for hospital mortality
      ranged from 1.9 (95% confidence interval 1.2-2.9) to 6.1 (95% confidence interval
      2.2-17). Requiring additional clinical signs beyond respiratory deterioration
      alone decreased event rates, had little impact on attributable lengths of stay,
      and diminished sensitivity and positive predictive values for hospital mortality.
      CONCLUSIONS: Objective surveillance definitions that include quantitative
      evidence of respiratory deterioration after a period of stability strongly
      predict increased length of stay and hospital mortality. These definitions merit
      further evaluation of their utility for hospital quality and safety improvement
      programs.

PMID- 22990453
TI  - Plant abiotic stress signaling.
AB  - Stress signaling is central to plants which--as immobile organisms--have to
      endure environmental fluctuations that constantly interfere with vigorous growth.
      As a result, plant-specific, elaborate mechanisms have evolved to perceive and
      respond to stress conditions. Currently, these stress responses are plausibly
      being revealed to involve crosstalks with energy signaling pathways as any growth
      limiting factor alters plant's energy status. Among these, autophagy,
      conventionally regarded as the mechanism whereby plants recycle and remobilize
      nutrients in bulk, has frequently been associated with stress responses. With the
      recent discoveries, however, autophagy has attained a novel role in stress
      signaling. In this review, major elements of abitoic stress signaling are
      summarized along with autophagy pathway, and in the light of recent discoveries,
      a putative, state-of-art role of autophagy is discussed.

PMID- 22990455
TI  - Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and
      outcome of the acute respiratory distress syndrome in children.
AB  - OBJECTIVES: The incidence and outcome of the acute respiratory distress syndrome
      in children are not well-known, especially under current ventilatory practices.
      The goal of this study was to determine the incidence, etiology, and outcome of
      acute respiratory distress syndrome in the pediatric population in the setting of
      lung protective ventilation. DESIGN: A 1-yr, prospective, multicenter,
      observational study in 12 geographical areas of Spain (serving a population of
      3.77 million <= 15 yrs of age) covered by 21 pediatric intensive care units.
      SUBJECTS: All consecutive pediatric patients receiving invasive mechanical
      ventilation and meeting American-European Consensus Criteria for acute
      respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Data on ventilatory management, gas exchange, hemodynamics, and organ
      dysfunction were collected. A total of 146 mechanically ventilated patients
      fulfilled the acute respiratory distress syndrome definition, representing a
      incidence of 3.9/100,000 population <= 15 yrs of age/yr. Pneumonia and sepsis
      were the most common causes of acute respiratory distress syndrome. At the time
      of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm
      Hg +/- 41 mm Hg, mean tidal volume was 7.6 mL/kg +/- 1.8 mL/kg predicted body
      weight, mean plateau pressure was 27 cm H2O +/- 6 cm H2O, and mean positive end
      expiratory pressure was 8.9 cm +/- 2.9 cm H2O. Overall pediatric intensive care
      unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and
      27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the
      assessment of oxygenation under standard ventilatory settings, 118 (80.8%)
      patients continued to meet acute respiratory distress syndrome criteria
      (PaO2/FIO2 104 mm Hg +/- 36 mm Hg; pediatric intensive care units mortality
      30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric
      intensive care units mortality 7.1%) (p = .014). CONCLUSIONS: This is the largest
      study to estimate prospectively the pediatric population-based acute respiratory
      distress syndrome incidence and the first incidence study performed during the
      routine application of lung protective ventilation in children. Our findings
      support a lower acute respiratory distress syndrome incidence and mortality than
      those reported for adults. PaO2/FIO2 ratios at acute respiratory distress
      syndrome onset and at 24 hrs after onset were helpful in defining groups at
      greater risk of dying (clinical trials registered with
      http://www.clinicaltrials.gov; NCT 01142544).

PMID- 22990456
TI  - Antitrypanosomal alkaloids from the marine bacterium Bacillus pumilus.
AB  - Fractionation of the ethyl acetate extract of the marine bacterium Bacillus
      pumilus isolated from the black coral Antipathes sp. led to the isolation of five
      compounds: cyclo-(L-Leu-L-Pro) (1), 3-hydroxyacetylindole (2), N-acetyl-beta
      oxotryptamine (3), cyclo-(L-Phe-L-Pro) (4), and 3-formylindole (5). The
      structures of compounds 1-5 were established by spectroscopic analyses, including
      HRESITOF-MS and NMR (1H, 13C, HSQC, HMBC and COSY). Compounds 2, 3 and 5 caused
      the inhibition on the growth of Trypanosoma cruzi (T. cruzi), with IC50 values of
      20.6, 19.4 and 26.9 MUM, respectively, with moderate cytotoxicity against Vero
      cells. Compounds 1-5 were found to be inactive when tested against Plasmodium
      falciparum and Leishmania donovani, therefore showing selectivity against T.
      cruzi parasites.

PMID- 22990457
TI  - Antioxidant profile of Trifolium pratense L.
AB  - In order to examine the antioxidant properties of five different extracts of
      Trifolium pratense L. (Leguminosae) leaves, various assays which measure free
      radical scavenging ability were carried out: 1,1-diphenyl-2-picrylhydrazyl,
      hydroxyl, superoxide anion and nitric oxide radical scavenger capacity tests and
      lipid peroxidation assay. In all of the tests, only the H2O and (to some extent)
      the EtOAc extracts showed a potent antioxidant effect compared with BHT and BHA,
      well-known synthetic antioxidants. In addition, in vivo experiments were
      conducted with antioxidant systems (activities of GSHPx, GSHR, Px, CAT, XOD, GSH
      content and intensity of LPx) in liver homogenate and blood of mice after their
      treatment with extracts of T. pratense leaves, or in combination with CCl4.
      Besides, in the extracts examined the total phenolic and flavonoid amounts were
      also determined, together with presence of the selected flavonoids: quercetin,
      luteolin, apigenin, naringenin and kaempferol, which were studied using a HPLC
      DAD technique. HPLC-DAD analysis showed a noticeable content of natural products
      according to which the examined Trifolium pratense species could well be regarded
      as a promising new source of bioactive natural compounds, which can be used both
      as a food supplement and a remedy.

PMID- 22990459
TI  - Antenatal surveillance of fetal growth restriction.
AB  - Fetal growth restriction is a complex problem in modern obstetrics. It is a
      condition of suboptimal fetal growth based on a genetically predetermined
      potential and affects approximately 5% to 10% of pregnancies. It is traditionally
      defined as an estimated fetal weight less than the 10th percentile. Those
      pregnancies that are affected by growth restriction are associated with increased
      risk of perinatal morbidity and mortality. Because of this increased risk, these
      pregnancies are monitored more closely to try to identify those fetuses at the
      greatest risk of fetal demise and initiate delivery before this critical event.
      Although the ideal management strategy is still being determined, there are
      several modalities available to assist in assessment of the growth-restricted
      fetus. These include the nonstress test test, biophysical profile, and Doppler
      velocimetry, most commonly of the fetal umbilical artery, in addition to
      sonographic growth assessment. The use of multiple fetal assessment tools may
      help improve the prediction of adverse outcomes and initiate delivery before
      cardiovascular collapse.

PMID- 22990458
TI  - The role of Mg2+ in immune cells.
AB  - The physiological and clinical relevance of Mg(2+) has evolved over the last
      decades. The molecular identification of multiple Mg(2+) transporters (Acdp2,
      MagT1, Mrs2, Paracellin-1, SLC41A1, SLC41A2, TRPM6 and TRPM7) and their
      biophysical characterization in recent years has improved our understanding of
      Mg(2+) homeostasis regulation and has provided a basis for investigating the role
      of Mg(2+) in the immune system. Deletions and mutations of Mg(2+) transporters
      produce severe phenotypes with more systemic symptoms than those seen with Ca(2+)
      channel deletions, which tend to be more specific and less profound. Deficiency
      of the Mg(2+) permeable ion channels TRPM6 or TRPM7 in mice is lethal at
      embryonic day 12.5 or at day 6.5, respectively, and, even more surprisingly,
      chicken DT40 B cells lacking TRPM7 die after 24-48 h. Recent progress made in
      Mg(2+) research has helped to define underlying mechanisms of two hereditary
      diseases, human Hypomagnesemia (TRPM6 deletion) and X-chromosomal
      immunodeficiency (MagT1 deletion), and has revealed a potential new role for
      Mg(2+) as a second messenger. Future elucidation of human Mg(2+) transporters
      (Mrs2, SLC41A1, SLC41A2, TRPM7) expressed in immunocytes, beyond MagT1 and TRPM6,
      will widen our knowledge about the potential role of Mg(2+) in the activation of
      the immune response.

PMID- 22990460
TI  - Reproductive outcomes after assisted conception.
AB  - The last three decades have witnessed a dramatic increase in the use of assisted
      reproductive technology (ART) so that now, in developed countries, 1.7% to 4.0%
      of all children are born after ART. Although absolute risks appear small, data
      from prospective and retrospective studies indicate increased risks of adverse
      maternal and perinatal outcomes after ART as compared with spontaneous
      conception. Recent studies suggest that underlying maternal factors and
      subfertility play an important role in some of these outcomes rather than the ART
      procedure itself. A significant risk of assisted conception is multiple
      pregnancies, but even singleton pregnancies achieved by ART are at a higher risk
      of hypertensive disease, diabetes, prematurity, low birth weight, and perinatal
      mortality even after adjusting for confounders. Couples undergoing ART procedures
      should be counseled in advance regarding increased risks of pregnancy
      complications and higher rates of obstetric interventions. Although conflicting
      data exist, studies of children born from ART suggest increased rates of
      congenital malformations, imprinting disorders (Beckwith-Wiedemann syndrome and
      Angelman syndrome), and marginally increased risk of cancer. However, the current
      evidence is inadequate, and prospective long-term studies are needed to eliminate
      the effect of confounders and draw definite conclusions about the long-term
      outcomes after ART. The absolute risk of imprinting disorders remains small, and
      routine screening is not recommended at present. The long-term outcomes after ART
      are difficult to evaluate because of the variability in ART methods and data
      reporting, and there is a need for standardized methodology for follow-up after
      ART.

PMID- 22990461
TI  - Interpregnancy interval and obstetrical complications.
AB  - Obstetricians are often presented with questions regarding the optimal
      interpregnancy interval (IPI). Short IPI has been associated with adverse
      perinatal and maternal outcomes, ranging from preterm birth and low birth weight
      to neonatal and maternal morbidity and mortality. Long IPI has in turn been
      associated with increased risk for preeclampsia and labor dystocia. In this
      review, we discuss the data regarding these associations along with recent
      studies revealing associations of short IPI with birth defects, schizophrenia,
      and autism. The optimal IPI may vary for different subgroups. We discuss the
      consequences of short IPI in women with a prior cesarean section, in particular
      the increased risk for uterine rupture and the considerations regarding a trial
      of labor in this subgroup. We review studies examining the interaction between
      short IPI and advanced maternal age and discuss the risk-benefit assessment for
      these women. Finally, we turn our attention to women after a stillbirth or an
      abortion, who often desire to conceive again with minimal delay. We discuss
      studies speaking in favor of a shorter IPI in this group. The accumulated data
      allow for the reevaluation of current IPI recommendations and management
      guidelines for women in general and among subpopulations with special
      circumstances. In particular, we suggest lowering the current minimal IPI
      recommendation to only 18 months (vs 24 months according to the latest World
      Health Organization recommendations), with even shorter recommended minimal IPI
      for women of advanced age and those who conceive after a spontaneous or induced
      abortion.

PMID- 22990462
TI  - Inhibition of Fe-induced colon oxidative stress by lactobacilli in mice.
AB  - Iron (Fe) can promote hydrogen peroxide (H(2)O(2)) and hydroxyl radical
      generation in the colonic surface and promote growth of Fe-dependent bacteria.
      Some Lactobacillus strains are resistant to oxygen free-radicals, allowing them
      to survive in a Fe-modulated mucosal environment and influence colon microbial
      ecology and redox state. Here, we investigated the capacity of lactobacilli with
      different antioxidant abilities to modify the bacterial profile and prevent
      oxidative stress in the colon of Fe-overloaded mice. Survival time of
      Lactobacillus rhamnosus LGG (LGG) in the presence of H(2)O(2) and hydroxyl
      radical was significantly longer compared with the mid- and non-antioxidative
      strains, Lactobacillus paracasei Fn032 and Lactobacillus plantarum Fn001,
      respectively. Different Lactobacillus strains are specific in free-radical
      scavenging activities of their cell-free extracts, which increased to varying
      extent depending on strains when bacteria were exposed to simulated gastric and
      pancreatic juice. Fe-overloaded mice showed increased colonic luminal ferrous Fe
      content, Enterococcus and Escherichia coli concentrations, mucosal
      malondialdehyde and free-radicals, and decreased mucosal total antioxidative
      capacity and oxidative enzymatic activity. Translocation of endotoxin to the
      liver was also significantly increased (P < 0.05). Lactobacilli inhibited ferrous
      Fe accumulation, especially in LGG and Fn032. LGG significantly inhibited the
      increase of colonic mucosal free-radicals and malondialdehyde content (P < 0.05).
      Fn032 only inhibited malondialdehyde (P < 0.05). LGG and Fn032 significantly
      inhibited increases in colonic Enterococcus (P < 0.05). Fn001 showed no
      significant antioxidative ability in vivo. The difference of these effects in
      vivo were well agreed with scavenging activities against reactive oxygen species
      (ROS) of simulated gastrointestinals fluid pretreated cells in vitro. In
      conclusion, ROS scavenging activities was essential for Lactobacillus to prevent
      oxidative stress in vivo and inhibition of ROS-producing bacterial growth and
      mucosal barrier injury.

PMID- 22990463
TI  - Can nutritional modulation of maternal intestinal microbiota influence the
      development of the infant gastrointestinal tract?
AB  - The gastrointestinal microbiota plays an important role in maintaining host
      health by preventing the colonization of pathogens, fermenting dietary compounds,
      and maintaining normal mucosal immunity. Particularly in early life, the
      composition of the microbiota profoundly influences the development and
      maturation of the gastrointestinal tract (GIT) mucosa, which may affect health in
      later life. Therefore, strategies to manipulate the microbiota during infancy may
      prevent the development of some diseases later in adult life. Earlier research
      suggested that term fetuses are sterile and that the initial bacterial
      colonization of the newborn GIT occurs only after the baby transits through the
      birth canal. However, recent studies have demonstrated that the colonization
      and/or contact of the fetus with the maternal GIT microbiota may start in utero.
      After vaginal birth, the colonization of the neonate GIT continues through
      contact with maternal feces and vaginal bacteria, leading to a relatively simple
      microbial community that is influenced by feeding type (breast vs. formula
      feeding). Maternal GIT microbiota, vaginal microbiota, and breast milk
      composition are influenced by maternal diet. Alterations of the maternal GIT
      microbiota composition via supplementation with probiotics and prebiotics have
      been shown; however, transfer of these benefits to the offspring remains to be
      demonstrated. This review focuses on the influence of maternal GIT microbiota
      during the pre- and postpartum periods on the colonization of the infant GIT. In
      particular, it examines the manipulation of the maternal GIT microbiota
      composition through the use of probiotics and/or prebiotics and subsequent
      consequences for the health of the offspring.

PMID- 22990464
TI  - Phytic acid-to-iron molar ratio rather than polyphenol concentration determines
      iron bioavailability in whole-cowpea meal among young women.
AB  - Limited data exist on iron absorption from NaFeEDTA and FeSO(4) in legume-based
      flours. The current study compared iron absorption from NaFeEDTA and FeSO(4) as
      fortificants within and between red and white varieties of cowpea with different
      concentrations of polyphenols (PP) but similar phytic acid (PA)-to-iron molar
      ratios. We performed a paired crossover study in young women (n = 16). Red-cowpea
      (high-PP) and white-cowpea (low-PP) test meals (Tubani) were each fortified with
      ((57)Fe)-labeled NaFeEDTA or ((58)Fe)-labeled FeSO(4) and were randomly
      administered. Iron absorption was measured as erythrocyte incorporation of stable
      iron isotopes. Per serving, the mean (+/-SD) PP concentrations of the white- and
      red-cowpea-based meals were 74 +/- 3.6 and 158 +/- 1.8 mg, respectively, and the
      molar ratio of PA to iron was 3.0 and 3.3. Iron bioavailabilities from red and
      white cowpeas were 1.4 and 1.7%, respectively, in NaFeEDTA-fortified meals and
      0.89 and 1.2%, respectively, in FeSO(4)-fortified meals. Compared with FeSO(4),
      fortification with NaFeEDTA increased the amount of iron absorbed from either of
      the cowpea meals by 0.05 to 0.08 mg (P < 0.05). Irrespective of the fortificant
      used, there was no significant difference in the amount of iron absorbed from the
      2 varieties of cowpea. The results suggest that NaFeEDTA is more bioavailable in
      legume-based flours compared with FeSO(4). In cowpea-based flours, the major
      determinant of low iron absorption may be the high molar ratio of PA to iron and
      not variations in PP concentration.

PMID- 22990465
TI  - Behavior and monoamine deficits in prenatal and perinatal iron deficiency are not
      corrected by early postnatal moderate-iron or high-iron diets in rats.
AB  - Developmental iron deficiency anemia (IDA) causes brain and behavioral deficits
      in rodent models, which cannot be reversed when treated at periods equivalent to
      later infancy in humans. This study sought to determine whether earlier iron
      treatment can normalize deficits of IDA in rats and what iron dose is optimal.
      The offspring of dams with IDA during gestation were cross-fostered at postnatal
      d (P) 8 to dams receiving diets with 1 of 3 iron concentrations until weaning
      (P21): 0.003-0.01 g/kg [totally iron deficient (TID)]; 0.04 g/kg [formerly iron
      deficient (FID-40)]; or 0.4 g/kg (FID-400). Always iron-sufficient control dams
      (CN-40) received a 0.04-g/kg iron diet. At P21, TID pups received a 0.01 g
      iron/kg diet; all others received a 0.04 g iron/kg diet. Hematocrit and brain
      iron and monoamine concentrations were assessed at P21 and P100. Pup growth,
      development, activity, object recognition, hesitancy, and watermaze performance
      were evaluated. Regional brain iron was restored by iron treatment. Regional
      monoamine and metabolite concentrations were elevated in FID-40 rats and reduced
      in FID-400 and TID rats compared with CN-40 rats. FID-40 offspring had motor
      delays similar to TID during lactation and FID-400 rats had elevated thigmotaxis
      similar to TID rats at P25 and P100 in the spatial watermaze. In conclusion, iron
      treatment at P8 in rats did not normalize all monoamine or behavioral measures
      after early IDA. Moderate iron treatment improved adult behavior, but higher iron
      treatment caused brain and behavioral patterns similar to TID in the short and
      long term.

PMID- 22990466
TI  - Duodenal reductase activity and spleen iron stores are reduced and erythropoiesis
      is abnormal in Dcytb knockout mice exposed to hypoxic conditions.
AB  - Duodenal cytochrome b (Dcytb, Cybrd1) is a ferric reductase localized in the
      duodenum that is highly upregulated in circumstances of increased iron
      absorption. To address the contribution of Dcytb to total duodenal ferric
      reductase activity as well as its wider role in iron metabolism, we first
      measured duodenal ferric reductase activity in wild-type (WT) and Dcytb knockout
      (Dcytb(-/-)) mice under 3 conditions known to induce gut ferric reductase:
      dietary iron deficiency, hypoxia, and pregnancy. Dcytb(-/-) and WT mice were
      randomly assigned to control (iron deficiency experiment, 48 mg/kg dietary iron;
      hypoxia experiment, normal atmospheric pressure; pregnancy experiment,
      nonpregnant animals) or treatment (iron deficiency experiment, 2-3 mg/kg dietary
      iron; hypoxia experiment, 53.3 kPa pressure; pregnancy experiment, d 20 of
      pregnancy) groups and duodenal reductase activity measured. We found no induction
      of ferric reductase activity in Dcytb(-/-) mice under any of these conditions,
      indicating there are no other inducible ferric reductases present in the
      duodenum. To test whether Dcytb was required for iron absorption in conditions
      with increased erythropoietic demand, we also measured tissue nonheme iron levels
      and hematological indices in WT and Dcytb(-/-) mice exposed to hypoxia. There was
      no evidence of gross alterations in iron absorption, hemoglobin, or total liver
      nonheme iron in Dcytb(-/-) mice exposed to hypoxia compared with WT mice.
      However, spleen nonheme iron was significantly less (6.7 +/- 1.0 vs. 12.7 +/- 0.9
      nmol . mg tissue(-1); P < 0.01, n = 7-8) in hypoxic Dcytb(-/-) compared with
      hypoxic WT mice and there was evidence of impaired reticulocyte hemoglobinization
      with a lower reticulocyte mean corpuscular hemoglobin (276 +/- 1 vs. 283 +/- 2 g
      . L(-1); P < 0.05, n = 7-8) in normoxic Dcytb(-/-) compared with normoxic WT
      mice. We therefore conclude that DCYTB is the primary iron-regulated duodenal
      ferric reductase in the gut and that Dcytb is necessary for optimal iron
      metabolism.

PMID- 22990468
TI  - Contributions of processed foods to dietary intake in the US from 2003-2008: a
      report of the Food and Nutrition Science Solutions Joint Task Force of the
      Academy of Nutrition and Dietetics, American Society for Nutrition, Institute of
      Food Technologists, and International Food Information Council.
AB  - Processed foods are an integral part of American diets, but a comparison of the
      nutrient contribution of foods by level of processing with the recommendations of
      the Dietary Guidelines for Americans regarding nutrients to encourage or to
      reduce has not been documented. The mean reported daily dietary intakes of these
      nutrients and other components were examined among 25,351 participants >=2 y of
      age in the 2003-2008 NHANES to determine the contribution of processed food to
      total intakes. Also examined was the percent contribution of each nutrient to the
      total reported daily nutrient intake for each of the 5 categories of food that
      were defined by the level of processing. All processing levels contributed to
      nutrient intakes, and none of the levels contributed solely to nutrients to be
      encouraged or solely to food components to be reduced. The processing level was a
      minor determinant of individual foods' nutrient contribution to the diet and,
      therefore, should not be a primary factor when selecting a balanced diet.

PMID- 22990467
TI  - The Niemann-Pick C1 gene is downregulated in livers of C57BL/6J mice by dietary
      fatty acids, but not dietary cholesterol, through feedback inhibition of the
      SREBP pathway.
AB  - The Niemann-Pick C1 (NPC1) gene is associated with human obesity. Mouse models
      with decreased Npc1 gene dosage are susceptible to weight gain when fed a high
      fat diet, but not a low-fat diet, consistent with an Npc1 gene-diet interaction.
      The objectives of this study were to define regulation of the Npc1 gene and to
      investigate the Npc1 gene-diet interaction responsible for weight gain. The
      experimental design involved feeding C57BL/6J male mice a low-fat diet (with
      0.00, 0.10, or 1.00% cholesterol) or a high-fat diet (with 0.02% cholesterol)
      until 30 wk to determine regulation of the Npc1 gene in liver. The key results
      showed that the Npc1 gene was downregulated by dietary fatty acids (54%, P =
      0.022), but not by dietary cholesterol, through feedback inhibition of the sterol
      regulatory element-binding protein (SREBP) pathway. However, the dietary fatty
      acids secondarily increased liver cholesterol, which also inhibits the SREBP
      pathway. Similarly, the Npc1 gene was downregulated in peritoneal fibroblasts
      isolated from C57BL/6J weanling male mice not exposed to the experimental diets
      and incubated in media supplemented with purified oleic acid (37%, P = 0.038) but
      not in media supplemented with purified cholesterol. These results are important
      because they suggest a novel mechanism for the interaction of fatty acids with
      the Npc1 gene to influence energy balance and to promote weight gain. Moreover,
      the responsiveness of the Npc1 gene to fatty acids is consistent with studies
      that suggest that the encoded NPC1 protein has a physiologic role in regulating
      both cholesterol and fatty acid metabolism.

PMID- 22990469
TI  - Maternal weight and body composition during pregnancy are associated with
      placental and birth weight in rural Bangladesh.
AB  - Placental growth is a strong predictor of fetal growth, but little is known about
      maternal predictors of placental growth in malnourished populations. Our
      objective was to investigate in a prospective study the associations of maternal
      weight and body composition [total body water (TBW) estimated by bioelectrical
      impedance and fat and fat-free mass derived from upper arm fat and muscle areas
      (UAFA, UAMA)] and changes in these with placental and birth weights. Within a
      cluster-randomized trial of maternal micronutrient supplementation, a subsample
      of 350 women was measured 3 times across gestation. Longitudinal analysis was
      used to examine independent associations of ~10-wk measurements and ~10-20 wk and
      ~20-32 wk changes with birth outcomes. Weight, TBW, and UAMA, but not UAFA, at
      ~10 wk were each positively and independently associated with placental weight
      and birth weight (P < 0.05). Of the maternal ~10-20 wk changes in measurements,
      only TBW change and placental weight, and maternal weight and birth weight were
      positively associated (P < 0.05). Gains in weight, TBW, and UAMA from 20 to 32 wk
      were positively and UAFA gain was negatively associated with placental weight (P
      <= 0.01). Gains in weight and UAMA from 20 to 32 wk were positively associated
      with birth weight (P <= 0.01). Overall, higher maternal weight and measures of
      fat-free mass at ~10 wk gestation and gains from 20 to 32 wk are independently
      associated with higher placental and birth weight.

PMID- 22990472
TI  - Arsenic-induced toxicity and carcinogenicity: a two-wave cross-sectional study in
      arsenicosis individuals in West Bengal, India.
AB  - In the state of West Bengal in India, over 26 million individuals are exposed to
      arsenic via drinking water. Dermatological, non-dermatological disorders and
      cancers are associated with arsenic toxicity. Of late, there has been a decrease
      in the arsenic concentration in drinking water owing to governmental efforts,
      raising the possibility of remediation. A cross-sectional study was conducted,
      where 189 arsenicosis and 171 unexposed individuals were recruited at two time
      points, (2005-06 and 2010-11) with concomitant decrease in the level of arsenic
      exposure via drinking water in the arsenicosis group in 2010-11. Parameters
      studied included dermatological, non-dermatological health status and cytogenetic
      damage. Decrease of arsenic exposure (190.1 MUg/l to 37.94 MUg/l) resulted in
      significant decline in the number of individuals having dermatological disorders
      (P<0.01) and in the severity of each dermatological outcome (P<0.0001).
      Micronucleus formation in urothelial cells and lymphocytes decreased
      significantly (P<0.001). However, there was a significant (P<0.001) rise in the
      incidence of each of the non-dermatological diseases, that is, peripheral
      neuropathy, conjunctivitis and respiratory distress over the period. Thirteen
      (6.87%) of the initially recruited arsenicosis individuals died of cancer, in
      this period. Remediation by arsenic-safe drinking water can reduce dermatological
      manifestations and cytogenetic insult; but is unable to counter the non
      dermatological symptoms.

PMID- 22990473
TI  - Nanomaterials design and tests for neural tissue engineering.
AB  - Nanostructured scaffolds recently showed great promise in tissue engineering:
      nanomaterials can be tailored at the molecular level and scaffold morphology may
      more closely resemble features of extracellular matrix components in terms of
      porosity, framing and biofunctionalities. As a consequence, both biomechanical
      properties of scaffold microenvironments and biomaterial-protein interactions can
      be tuned, allowing for improved transplanted cell engraftment and better
      controlled diffusion of drugs. Easier said than done, a nanotech-based
      regenerative approach encompasses different fields of know-how, ranging from in
      silico simulations, nanomaterial synthesis and characterization at the nano-,
      micro- and mesoscales to random library screening methods (e.g. phage display),
      in vitro cellular-based experiments and validation in animal models of the target
      injury. All of these steps of the "assembly line" of nanostructured scaffolds are
      tightly interconnected both in their standard analysis techniques and in their
      most recent breakthroughs: indeed their efforts have to jointly provide the
      deepest possible analyses of the diverse facets of the challenging field of
      neural tissue engineering. The purpose of this review is therefore to provide a
      critical overview of the recent advances in and drawbacks and potential of each
      mentioned field, contributing to the realization of effective nanotech-based
      therapies for the regeneration of peripheral nerve transections, spinal cord
      injuries and brain traumatic injuries. Far from being the ultimate overview of
      such a number of topics, the reader will acknowledge the intrinsic complexity of
      the goal of nanotech tissue engineering for a conscious approach to the
      development of a regenerative therapy and, by deciphering the thread connecting
      all steps of the research, will gain the necessary view of its tremendous
      potential if each piece of stone is correctly placed to work synergically in this
      impressive mosaic.

PMID- 22990474
TI  - Temporal trends and determinants of peripartum hysterectomy in Lombardy, Northern
      Italy, 1996-2010.
AB  - PURPOSE: To analyze the temporal trends of peripartum hysterectomy (PH) in the
      period 1996-2010 in Lombardy, Italy. METHODS: Using data from the Regional
      Database, PH ratios/1,000 deliveries were calculated from 1996 to 2010, in strata
      of age and mode of delivery among women resident in Lombardy, Italy. PH cases
      were identified searching the database for the ICD-9 and ICD-10 codes for
      subtotal and total hysterectomy. PH ratios/1,000 deliveries in strata of age,
      mode of delivery and calendar year were computed. Poisson's regression analysis
      was used to test trend over time. RESULTS: A total of 905 PH and 1,289,163
      deliveries were recorded between 1996 and 2010. The overall PH ratio was
      0.70/1,000 deliveries. The PH ratio/1,000 deliveries increased over time, being
      0.57 in 1996 and 0.88/1,000 deliveries in 2010 (P < 0.0001). After including
      calendar year, mode of delivery and maternal age in the Poisson's regression
      equation, no significant linear trend emerged in the PH ratio over time (P =
      0.28). Women who underwent cesarean section (CS) (CS vs. vaginal delivery: OR
      5.66, 95 % CI 4.91-6.54) and older women were at increased risk of PH (maternal
      age >=40 vs. <30 years: OR 5.66, 95 % CI 4.48-7.15). The frequency of intractable
      peripartum hemorrhage and placenta praevia/accreta, the main indications for PH,
      significantly increased over the study period. CONCLUSIONS: In Lombardy, the PH
      ratio increased between 1996 and 2010. In our population, rising frequency of CS
      and older maternal age may explain this trend.

PMID- 22990475
TI  - Should factor V Leiden mutation and prothrombin gene polymorphism testing be done
      in women with recurrent miscarriage from North India?
AB  - PURPOSE: Role of thrombophilic factor (FV) in the etiology of recurrent
      miscarriages is not confirmed till date. It has been hypothesized that
      thrombophilic G1691A factor V Leiden (FVL), if detected well ahead in time among
      recurrent miscarriages may be a treatable. The role of FVL mutation in the
      pathogenesis of sporadic and recurrent miscarriages among North Indian women was
      studied to construct the frequency data in this part of the country. Further, we
      have evaluated the cost-benefit factor. METHODS: This is a case-control study,
      women with recurrent miscarriages (n = 1,000) as cases and healthy parous women
      (n = 500) as controls were enrolled in the study between January 2003 and January
      2012. DNA was extracted from peripheral blood and analyzed for the presence of
      FVL mutation and prothrombin gene polymorphism (G20210A). We have carried out the
      meta-analysis taking into consideration 20 other world populations. RESULTS: In
      total, 50 (5.0 %) cases and 12 (2.4 %) controls were heterozygous for the FVL
      mutation. The incidence of FVL was higher in recurrent miscarriage cases as
      compared to the control group (OR 2.14; 95 % CI 1.12-4.05). CONCLUSION: Our
      results revealed the absence of FVL mutation in a homozygous state among patients
      and controls. Although the heterozygous mutation is almost double in cases as
      compared to controls, we still suggest that looking at the cost-benefit analysis
      this test may not be included in the battery of tests performed on recurrent
      miscarriages among North Indians from this part of the country.

PMID- 22990476
TI  - Birth injury after cesarean section at 24 weeks of gestation: a large scalp
      laceration.

PMID- 22990477
TI  - Single-port laparoscopic myomectomy: initial operative experience and comparative
      outcome.
AB  - OBJECTIVE: To present the initial operative outcome and comparative data among
      patients undergoing single-port laparoscopic myomectomy (SPLM). MATERIALS AND
      METHODS: A prospective, observational study of all patients who underwent SPLM
      was performed. The demographic and operative data, including age, body mass
      index, operative indications, operative time, estimated blood loss,
      complications, and postoperative hospital stay were recorded. A match cohort of
      patients undergoing traditional LM was also retrospectively compared. RESULTS:
      SPLM was successfully performed in all ten patients from April 2010 to October
      2010. The two groups (SPLM and traditional LM) were matched by age, body mass
      index, size, and weight of fibroids. The median operating time (196.5 vs. 82.5
      min, P < 0.001) and length of hospitalization (3 vs. 2 days, P = 0.042) were
      significantly longer in SPLM group than in traditional LM group. The median
      operative blood loss was not significantly different. No patients in either group
      had serious complications. CONCLUSION: Despite the increased operating time, SPLM
      is feasible and offers comparable surgical outcomes and superior cosmesis
      compared with traditional LM.

PMID- 22990478
TI  - A small-molecular europium complex with anion sensing sensitivity.
AB  - A novel small-molecular europium(III) complex with quinoline derivative has been
      designed and prepared for anion recognition. This Eu(3+) complex displays
      striking emission changes at 616 nm in response to NO(3)(-) and Cl(-). What's
      more, the anion-selective luminescence enhancement is easily detected by the
      naked eye. UV, luminescence titration experiments and the Job plot analysis
      revealed that the ligand can form stable 1 : 1 complexes with Eu(NO(3))(3) or
      EuCl(3) in CH(3)CN; log K = 7.10 and 6.76 (295 K), respectively. The crystal
      structure shows that three oxygen atoms and one nitrogen atom of the ligand are
      approximately coplanar and wrap around the Eu(3+) ion through a semicircle-shaped
      coordination structure and some unoccupied sites of the central europium ions are
      available for guest anions in the complexes. Thus, three nitrate ions are located
      in the gap of the semicircle. It is supposed that the mechanism of luminescence
      enhancement is of NO(3)(-) or Cl(-) anions squeezing out solvent molecules from
      the inner coordination sphere.

PMID- 22990479
TI  - Increased mercury and body size and changes in trophic structure of Gambusia
      puncticulata (Poeciliidae) along the Almendares River, Cuba.
AB  - The Almendares River is the largest river draining the area around Havana City,
      Cuba. The watershed is heavily populated and industrialized, which has had a
      significant impact on the flow and water quality of the river. The main goal of
      this study was to analyze the spatial variability in dietary habits, nutrient
      flow (using stable isotope ratios delta(15)N and delta(13)C), and mercury (Hg)
      levels along the Almendares River upstream and downstream of point-source
      discharges using localized fish Gambusia puncticulata. Stomach contents of G.
      puncticulata were similar among these sites. However, mean delta(15)N values
      ranged from 6 to 18 0/00 across sites and were lower in fish from downstream than
      upstream sites, suggesting localized influences of nutrient inputs along the
      river. delta(13)C values were between -22 and -25 0/00, except at a mid-basin
      site (-26 to -270/00), indicating that fish relied on similar carbon sources at
      most sites. Total mercury concentrations ranged from 0.04 to 0.49 MUg/g wet
      weight whole body and were unrelated to the among-site differences in delta(15)N,
      but Hg exceeded the threshold considered to be protective of fish health (0.2
      MUg/g ww whole body) in the majority of fish from all sites but one. Results of
      this study indicate that although the dietary habits of this species do not vary
      across sites, tissue differences in delta(15)N, delta(13)C and Hg show little
      movement of this species among sites. Localized effects of human activities on
      nutrients and metals may be affecting the health of this species and posing a
      risk to other consumers in the ecosystem.

PMID- 22990480
TI  - Zinc distribution in the organs of adult Fundulus heteroclitus after waterborne
      zinc exposure in freshwater and saltwater.
AB  - Zinc (Zn) is an essential micronutrient to aquatic organisms, but increased
      concentrations may result in accumulation and toxic effects. Water chemistry is
      known to influence the uptake of Zn in aquatic biota; therefore, organisms
      inhabiting environments with variable salinities may exhibit different patterns
      of Zn accumulation. Likewise, metal uptake can vary in fish as a consequence of
      ionoregulatory status (acclimated to freshwater or saltwater). The euryhaline
      fish, Fundulus heteroclitus, was exposed to a control and two increased Zn
      concentrations (15 and 75 MUg/L in moderately hard freshwater and 100 and 1,000
      MUg/L in 35 g/L saltwater) for 7 days. The ionic Zn concentrations were
      equivalent in the 75 MUg/L Zn treatment in freshwater and the 100 MUg/L Zn
      treatment in saltwater. Throughout the 7-day experiments, fish were dissected,
      and organ Zn distribution was quantified in the gill, intestine, liver, gall
      bladder, heart, and carcass. Different patterns of Zn accumulation were observed
      in F. heteroclitus dependent on exposure medium. Despite lower exposure
      concentrations, F. heteroclitus accumulated more Zn in freshwater than in
      saltwater in all of the organs analyzed with the exception of the carcass. In
      addition, there were correlations between Zn distribution and known physiological
      mechanisms related to osmoregulation in F. heteroclitus. Furthermore, this
      research suggests that F. heteroclitus are more susceptible to Zn accumulation in
      freshwater environments.

PMID- 22990481
TI  - Identifying active surface phases for metal oxide electrocatalysts: a study of
      manganese oxide bi-functional catalysts for oxygen reduction and water oxidation
      catalysis.
AB  - Progress in the field of electrocatalysis is often hampered by the difficulty in
      identifying the active site on an electrode surface. Herein we combine
      theoretical analysis and electrochemical methods to identify the active surfaces
      in a manganese oxide bi-functional catalyst for the oxygen reduction reaction
      (ORR) and the oxygen evolution reaction (OER). First, we electrochemically
      characterize the nanostructured alpha-Mn(2)O(3) and find that it undergoes
      oxidation in two potential regions: initially, between 0.5 V and 0.8 V, a
      potential region relevant to the ORR and, subsequently, between 0.8 V and 1.0 V,
      a potential region between the ORR and the OER relevant conditions. Next, we
      perform density function theory (DFT) calculations to understand the changes in
      the MnO(x) surface as a function of potential and to elucidate reaction
      mechanisms that lead to high activities observed in the experiments. Using DFT,
      we construct surface Pourbaix and free energy diagrams of three different MnO(x)
      surfaces and identify 1/2 ML HO* covered Mn(2)O(3) and O* covered MnO(2), as the
      active surfaces for the ORR and the OER, respectively. Additionally, we find that
      the ORR occurs through an associative mechanism and that its overpotential is
      highly dependent on the stabilization of intermediates through hydrogen bonds
      with water molecules. We also determine that OER occurs through direct
      recombination mechanism and that its major source of overpotential is the scaling
      relationship between HOO* and HO* surface intermediates. Using a previously
      developed Sabatier model we show that the theoretical predictions of catalytic
      activities match the experimentally determined onset potentials for the ORR and
      the OER, both qualitatively and quantitatively. Consequently, the combination of
      first-principles theoretical analysis and experimental methods offers an
      understanding of manganese oxide oxygen electrocatalysis at the atomic level,
      achieving fundamental insight that can potentially be used to design and develop
      improved electrocatalysts for the ORR and the OER and other important reactions
      of technological interest.

PMID- 22990482
TI  - The relation between experiential avoidance, alexithymia and emotion regulation
      in inpatient adolescents.
AB  - Recently, efforts have been made to better understand constructs that are
      associated with difficulties in emotion regulation in hopes of identifying
      underlying mechanisms that may be valuable targets for intervention. Against this
      background, the present study had two aims. Firstly, we wanted to explore the
      relation between emotion regulation, experiential avoidance and alexithymia by
      determining whether adolescents with elevated scores on a measure of alexithymia
      would report deficits in emotion regulation and experiential avoidance. Secondly,
      we sought to evaluate the role of experiential avoidance as a mediator in the
      relation between alexithymia and emotion regulation. The sample (N = 64)
      consisted of adolescents recruited from an inpatient facility of which
      approximately 30% were classified as having alexithymia. The results of this
      study indicate that adolescents with alexithymia report deficits in emotion
      regulation and elevated experiential avoidance. Experiential avoidance mediated
      the relation between alexithymia and emotion regulation, indicating that while
      the inability to effectively use language to identify and describe emotional
      states is strongly correlated with difficulties in regulating one's emotions,
      this relation is mediated by the unwillingness to tolerate aversive private
      experiences. Limitations and strengths of the present study are also noted. 

PMID- 22990484
TI  - Modernizing Natural History: Berkeley's Museum of Vertebrate Zoology in
      Transition.
AB  - Throughout the twentieth century calls to modernize natural history motivated a
      range of responses. It was unclear how research in natural history museums would
      participate in the significant technological and conceptual changes that were
      occurring in the life sciences. By the 1960s, the Museum of Vertebrate Zoology at
      the University of California, Berkeley, was among the few university-based
      natural history museums that were able to maintain their specimen collections and
      support active research. The MVZ therefore provides a window to the modernization
      of natural history. This paper concentrates on the directorial transitions that
      occurred at the MVZ between 1965 and 1971. During this period, the MVZ had four
      directors: Alden H. Miller (Director 1940-1965), an ornithologist; Aldo Starker
      Leopold (Acting Director 1965-1966), a conservationist and wildlife biologist;
      Oliver P. Pearson (Director 1966-1971), a physiologist and mammalogist; and David
      B. Wake (Director 1971-1998), a morphologist, developmental biologist, and
      herpetologist. The paper explores how a diversity of overlapping modernization
      strategies, including hiring new faculty, building infrastructure to study live
      animals, establishing new kinds of collections, and building modern laboratories
      combined to maintain collections at the MVZ's core. The paper examines the
      tensions between the different modernization strategies to inform an analysis of
      how and why some changes were institutionalized while others were short-lived. By
      exploring the modernization of collections-based research, this paper emphasizes
      the importance of collections in the transformation of the life sciences. 

PMID- 22990485
TI  - Effect of plant growth-promoting rhizobacteria (PGPRs) on plant growth, yield,
      and quality of tomato (Lycopersicon esculentum Mill.) under simulated seawater
      irrigation.
AB  - To determine the effects of three PGPRs on plant growth, yield, and quality of
      tomato under simulated seawater irrigation, a two consecutive seasons' field
      experiment was conducted in Yancheng Teachers University plot from April to June
      and August to October, 2011. The results showed that Erwinia persicinus RA2
      containing ACC deaminase exhibited the best ability compared with Bacillus
      pumilus WP8 and Pseudomonas putida RBP1 which had no ACC deaminase activity to
      enhance marketable yields of fresh and dried fruits in tomato under simulated
      seawater irrigation especially under HS condition. B. pumilus WP8 had significant
      effects on improving tomato fruit quality under the conditions of irrigating with
      1.0% NaCl solution (MS) and with 2.0% NaCl solution (HS). Na(+) contents were
      generally accumulated much more in tomato plant mid-shoot leaves than in fruits
      whatever the salt concentration. More sodium accumulation in leaves of E.
      persicinus RA2 and B. pumilus WP8 treatments under HS condition were found than
      in control. E. persicinus RA2 and B. pumilus WP8 can promote tomato growth,
      improve fruit quality more firmly than P. putida RBP1 during two consecutive
      seasons. Our study suggested that E. persicinus RA2 and B. pumilus WP8 are
      considered to be promising PGPR strains which are suited for application in salt
      marsh planting, ACC deaminase activity was not unique index on screening for
      PGPRs with the aim of salt stress tolerance, and plant growth promoting
      activities may be relevant to different growth indices and different stress
      conditions.

PMID- 22990486
TI  - Isolation, identification and characterization of a glyphosate-degrading
      bacterium, Bacillus cereus CB4, from soil.
AB  - A bacterial strain named CB4, with highly effective glyphosate degradation
      capability, was isolated from soil after enrichment. On the basis of the Biolog
      omniLog identification system (Biolog) and 16S ribosomal RNA (rRNA) gene
      sequencing methods, strain CB4 was identified as Bacillus cereus. Further
      experiments were carried out to optimize the growth of strain CB4 and the
      glyphosate degradation activity by high performance liquid chromatography (HPLC).
      The optimal conditions were found as follows: initial pH 6.0, incubation
      temperature 35 degrees C, glyphosate concentration 6 g L(-1), inoculation amount
      5% and incubation time 5 days. Under the optimal conditions, stain CB4 utilized
      94.47% of glyphosate. This is the first report on B. cereus with a capacity to
      utilize herbicide glyphosate, and it can degrade glyphosate concentrations up to
      12 g L(-1). Metabolization of glyphosate by strain B. cereus CB4 was studied.
      Results indicated that two concurrent pathways were capable of degrading
      glyphosate to AMPA, glyoxylate, sarcosine, glycine and formaldehyde as products.
      Glyphosate breakdown in B. cereus CB4 was achieved by the C-P lyase activity and
      the glyphosate oxidoreductase activity.

PMID- 22990487
TI  - Bacterial communities in fish sauce mash using culture-dependent and -independent
      methods.
AB  - In fish sauce production, microorganisms are associated with the fermentation
      process; however, the sequential changes in the bacterial communities have never
      been examined throughout the period of fermentation. In this study, we determined
      the bacterial floras in a fish sauce mash over 8 months, using three different
      culture media and 16S rRNA gene clone library analysis. During the first 4 weeks,
      viable counts of non-halophilic and halophilic bacteria decreased and were
      dominated by Staphylococcus species. Between 4 and 6 weeks, halophilic and highly
      halophilic bacterial counts markedly increased from 10(7) to 10(8) cfu/g, and the
      predominant species changed to Tetragenococcus halophilus. The occurrence of T.
      halophilus was associated with an increase of lactic acid and a reduction of pH
      values. In contrast, non-halophilic bacterial counts decreased to 10(6) cfu/g by
      6 weeks with Bacillus subtilis as the dominant isolate. Clone library analysis
      revealed that the dominant bacterial group also changed from Staphylococcus spp.
      to T. halophilus, and the changes were consistent with those of the floras of
      halophilic and highly halophilic isolates. This is the first report describing a
      combination approach of culture and clone library methods for the analysis of
      bacterial communities in fish sauce mash.

PMID- 22990488
TI  - YgiW homologous gene from Pseudomonas aeruginosa 25W is responsible for
      tributyltin resistance.
AB  - A tributyltin (TBT) resistance gene was isolated from the TBT-resistant marine
      origin bacterium Pseudomonas aeruginosa 25W. This gene was identical to PA0320
      deposited in the P. aeruginosa PAO1 database (http://www.pseudomonas.com). The
      deduced amino acid sequence of PA0320 appears to be homologous to the YgiW
      proteins of Escherichia coli and Salmonella enterica. The deletion mutant of
      PA0320 showed a reduction of growth rate in the presence of TBT. A susceptibility
      test to cadmium, mercury, hydrogen peroxide and acidic pH in the deletion mutant
      showed an increasing susceptibility to them. PA0320 plays a certain role in
      stress tolerance against TBT as well as in stressors producing reactive oxygen
      species.

PMID- 22990489
TI  - Addition of a palm oil analogue to oil-reservoir formation water stimulates the
      growth of Anaerobaculum sp. and a novel taxon from the Deferribacteraceae.
AB  - The manipulation of microbes within oil reservoirs has been the subject of a
      number of studies. The aims of these studies have included alteration of oil
      characteristics, improvement in recovery of oil and suppression of microbes that
      produce H(2)S. Understanding microbial communities and their microbial responses
      is important in predicting the outcome of these studies. Palm oil waste is an
      abundant waste product, particularly in Asia, and we sought to examine its
      usefulness for altering microbial communities in oil reservoirs. Data from the
      present study demonstrated that after amendment with a palm oil analogue (POA),
      oil reservoir microflora produced methane and nitrogen gas along with a net
      consumption of CO(2). The addition stimulated a novel taxon in the family
      Deferribacteraceae. Amendment with POA also affected the methanogen community by
      stimulating the growth of Methanothermobacter, Methanoculleus and Methanocalculus
      spp. Overall the study indicated that POA addition allowed the development of a
      consortium that was able to convert CO(2) into CH(4) in a process powered by an
      abundant waste product.

PMID- 22990490
TI  - Efficient and direct identification of fructose fermenting and non-fermenting
      bacteria from calf gut microbiota using stable isotope probing and modified T
      RFLP.
AB  - The aim of this study was the development of an efficient method to identify the
      prebiotics-assimilating-bacteria in gut microbiota using DNA-stable isotope
      probing (DNA-SIP) technology. For efficient probing of microbiota with stable
      isotopes, a small-scale repeated batch culture using a low-carbon-source
      containing medium was developed. Fecal samples from cattle were inoculated and [U
      (13)C]-fructose was applied to the culture after 24 h stabilization. Organic acid
      production, pH value of the period and the total diversity of microorganisms of
      the culture were successfully maintained during the chasing period. DNA samples
      were extracted from the culture and were subjected to isopycnic centrifugation
      and fractionation in order to separate fructose fermenters from non-fermenters. T
      RFLP (Terminal Restriction Fragment Length Polymorphism) and the modified T-RFLP
      of each fraction suggested that Streptococcus bovis was the most dominant
      fructose fermenter in this culture. In addition, we improved the modified T-RFLP
      method and successfully identified Lactobacillus vitulinus and Megasphaella
      eldenii as minor fructose-fermenters and several species of Clostridium cluster
      IV as non-fermenters. From these results we concluded that the methods shown here
      provide a means for assessing the importance of individual prebiotics on gut
      microbiota.

PMID- 22990491
TI  - Pedobacter kyungheensis sp. nov., with ginsenoside converting activity.
AB  - The Gram-negative, aerobic, non-motile, non-spore forming, and rod-shaped
      bacterium designated as THG-T17(T) was isolated from the soil of a ginseng field
      of Pocheon in Korea, and its taxonomic position was investigated by using a
      polyphasic approach. The growth of strain THG-T17(T) occurred at 4-40 degrees C
      and pH 4.0-9.0 with 1-2% (w/v) NaCl on nutrient agar. Strain THG-T17(T) displayed
      beta-glucosidase activity that was responsible for its ability to transform
      ginsenoside Rb(1) (one of the dominant ginsenosides of ginseng) to compound F2
      via gypenoside XVII. On the basis of 16S rRNA gene sequence similarity, strain
      THG-T17(T) was shown to belong to the genus Pedobacter and was related to
      Pedobacter soli 15-51(T) (98.8%), Pedobacter sandarakinus DS-27(T) (98.0%) and
      Pedobacter terrae DS-57(T) (98.1%). The G+C content of the genomic DNA was 42.4
      mol%. The DNA-DNA relatedness values between strain THG-T17(T) and its
      phylogenetically closest neighbors were below 14%. Phenotypic and chemotaxonomic
      data, especially analysis of cellular fatty acid, supported the affiliation of
      strain THG-T17(T) to the genus Pedobacter. The results of genotyping and
      biochemical tests showed strain THG-T17(T) to be differentiated genotypically and
      phenotypically from the recognized species of the genus Pedobacter. Therefore,
      the novel isolate represents a novel species, for which the name Pedobacter
      kyungheensis sp. nov. is proposed, with the type strain THG-T17(T) (=KACC
      16221(T) = LMG 26577(T)).

PMID- 22990492
TI  - Construction of a food-grade cloning vector for Lactobacillus plantarum and its
      utilization in a food model.
AB  - The development of Lactobacillus plantarum to be used in starter cultures in the
      food industry has been limited because of the lack of a food-grade cloning vector
      for the bacterium. In this study, the plasmid pFLP1 was constructed by joining 2
      DNA fragments derived from food-approved organisms. The 5.2-kb BamHI/KpnI DNA
      fragment of pRV566 containing the theta-type replicon of Lactobacillus sakei was
      ligated to the BamHI/KpnI DNA fragment of a 2.9-kb lactococcal cadmium resistance
      determinant amplified from pND918. The 8.1-kb newly constructed plasmid could
      transform L. plantarum N014, a bacteriocin-producing bacteria originally isolated
      from nham, a traditional Thai fermented sausage. The resulting transformant, L.
      plantarum N014-FLP, and its parent strain were shown to be very similar in growth
      rate and bacteriocin activity. In addition, the plasmid was very stable in its
      host bacteria under nonselective pressure for 100 generations in MRS medium and
      for 5 days in a nham model. These results suggest that pFLP1 is a potential food
      grade cloning vector for L. plantarum.

PMID- 22990493
TI  - Microscopic analysis of Cordyceps bassiana (anamorph stage: Beauveria bassiana)
      stromata during artificial cultivation for commercial use.

PMID- 22990494
TI  - The mitochondrial genome of the white-rot fungus Flammulina velutipes.

PMID- 22990495
TI  - Covalently linked polyamines in the cell wall peptidoglycan of the anaerobes
      belonging to the order Selenomonadales.

PMID- 22990496
TI  - Networking and knowledge exchange to promote the formation of transdisciplinary
      coalitions and levels of agreement among transdisciplinary peer reviewers.
AB  - CONTEXT: Funding for transdisciplinary chronic disease prevention research has
      increased over the past decade. However, few studies have evaluated whether
      networking and knowledge exchange activities promote the creation of
      transdisciplinary teams to successfully respond to requests for proposals (RFPs).
      Such evaluations are critical to understanding how to accelerate the integration
      of research with practice and policy to improve population health. OBJECTIVE: To
      examine (1) the extent of participation in pre-RFP activities among funded and
      nonfunded transdisciplinary coalitions that responded to a RFP for cancer and
      chronic disease prevention initiatives and (2) levels of agreement in proposal
      ratings among research, practice, and policy peer reviewers. DESIGN/SETTING:
      Descriptive report of a Canadian funding initiative to increase the integration
      of evidence with action. PARTICIPANTS: Four hundred forty-nine representatives in
      41 research, practice, and policy coalitions who responded to a RFP and whose
      proposals were peer reviewed by a transdisciplinary adjudication panel.
      INTERVENTION: The funder hosted 6 national meetings and issued a letter of intent
      (LOI) to foster research, practice, and policy collaborations before issuing a
      RFP. RESULTS: All provinces and territories in Canada were represented by the
      coalitions. Funded coalitions were 2.5 times more likely than nonfunded
      coalitions to submit a LOI. A greater proportion of funded coalitions were
      exposed to the pre-RFP activities (100%) compared with coalitions that were not
      funded (68%). Overall research, practice, and policy peer reviewer agreement was
      low (intraclass correlation 0.12). CONCLUSIONS: There is widespread interest in
      transdisciplinary collaborations to improve cancer and chronic disease
      prevention. Engagement in networking and knowledge exchange activities, and
      feedback from LOIs prior to submission of a final application, may contribute to
      stronger proposals and subsequent funding success. Future evaluations should
      examine best practices for transdisciplinary peer review to facilitate funding of
      proposals that on balance have both scientific rigor and are relevant to the real
      world.

PMID- 22990498
TI  - The art of aligning one-dimensional (1D) nanostructures.
AB  - One-dimensional (1D) nanostructures, including polymeric, small molecule and
      inorganic types, are currently being investigated in great detail for their
      unique mechanical, optical, electronic properties and potential implementation as
      devices. To integrate 1D nanostructures into device applications, it is of
      importance to align such nanostructures in a parallel, scalable, and highly
      reproducible manner independent of the specific materials. Well aligned 1D
      nanostructures might exhibit superior properties that are not found in their
      disordered counterparts, allowing promising applications in diverse fields. This
      critical review summarizes the recent work in the alignment of polymeric, small
      molecule and inorganic 1D nanostructures, in particular, the advantages and
      drawbacks of various aligning approaches. Discussion is focused on an advanced
      strategy to precisely position each 1D nanostructure by superhydrophobic pillar
      structured surfaces. The research prospects and directions of this rapidly
      developing field are also briefly addressed (123 references).

PMID- 22990499
TI  - The Lnk adaptor protein: a key regulator of normal and pathological
      hematopoiesis.
AB  - The development and function of blood cells are regulated by specific growth
      factors/cytokines and their receptors' signaling pathways. In this way, these
      factors influence cell survival, proliferation and differentiation of
      hematopoietic cells. Central to this positive and/or negative control are the
      adaptor proteins. Since their identification 10 years ago, members of the Lnk
      adaptor protein family have proved to be important activators and/or inhibitors
      in the hematopoietic, immune and vascular system. In particular, the generation
      of animal and cellular models for the Lnk and APS proteins has helped establish
      the physiological role of these molecules through the identification of their
      specific signaling pathways and the characterization of their binding partners.
      Moreover, the recent identification of mutations in the LNK gene in
      myeloproliferative disorders, as well as the correlation of a single nucleotide
      polymorphism on LNK with hematological, immune and vascular diseases have
      suggested its involvement in the pathophysiology of these malignancies. The
      latter findings have thus raised the possibility of addressing Lnk signaling for
      the treatment of certain human diseases. This review therefore describes the
      pathophysiological role of this adaptor protein in hematological malignancies and
      the potential benefits of Lnk therapeutic targeting.

PMID- 22990497
TI  - Protective actions of vitamin D in UVB induced skin cancer.
AB  - Non-melanoma skin cancers (NMSC) are the most common type of cancer, occurring at
      a rate of over 1 million per year in the United States. Although their metastatic
      potential is generally low, they can and do metastasize, especially in the immune
      compromised host, and their surgical treatment is often quite disfiguring.
      Ultraviolet radiation (UVR) as occurs with sunlight exposure is generally
      regarded as causal for these malignancies, but UVR is also required for vitamin D
      synthesis in the skin. Based on our own data and that reported in the literature,
      we hypothesize that the vitamin D produced in the skin serves to suppress UVR
      epidermal tumor formation. In this review we will first discuss the evidence
      supporting the conclusion that the vitamin D receptor (VDR), with or without its
      ligand 1,25-dihydroxyvitamin D, limits the propensity for cancer formation
      following UVR. We will then explore three potential mechanisms for this
      protection: inhibition of proliferation and stimulation of differentiation,
      immune regulation, and stimulation of DNA damage repair (DDR).

PMID- 22990501
TI  - Association of Raynaud's syndrome with interferons. A meta-analysis.
AB  - AIM: Vasospastic disorders of the digital circulation such as the Raynaud's
      syndrome (RS) are known side-effects of treatment of interferons. The prevalence
      of RS in patients during treatment with interferons agents is not well-defined.
      The objective of this paper was to assess the prevalence of RS in patients
      receiving interferons - a meta-analysis of published data was performed. METHODS:
      The PubMed database of the National Library of Medicine and ISI Web of Knowledge
      was used for studies dealing with RS and patients receiving interferons. The
      studies provided sufficient data to estimate the prevalence of RS in patients
      receiving interferons. A forest plot was determined by the revealed prevalences.
      Statistical analysis was based on methods for a random effects meta-analysis and
      a finite mixture model for proportions. Publication bias was investigated with
      the linear regression test (Egger's method). A meta-regression was conducted by
      the year of publication. RESULTS: Six eligible studies, contributing data on 183
      subjects, were included in this meta-analysis. For RS in patients receiving
      interferons a pooled prevalence of 13.6% and 95% CI (95% CI 0.026, 0.313) was
      obtained. A mixture model analysis found three latent classes. Statistically,
      publication bias was not present (p-value 0.335). CONCLUSION: Despite some
      heterogeneity there is a possible indication of an association between RS and
      patients receiving interferons.

PMID- 22990502
TI  - UIP 2011 C3 consensus.

PMID- 22990503
TI  - CEA versus CAS: short-term and mid-term results.
AB  - AIM: Ischemic stroke represents a major health problem and it is an important
      cause of long-term disability. The aim of this study was to compare short-term
      and mid-term results of carotid endarterectomy and stenting. METHODS: During a
      three-year period, we enrolled 300 patients with carotid stenosis that fit with
      Stroke Prevention and Educational Awareness Diffusion (SPREAD) guidelines and we
      performed 150 carotid endarterectomy operations (CEA) and 150 carotid artery
      stenting procedures (CAS) with distal protection devices. All patients underwent
      preoperative and postoperative: neurological examination, ultrasound imaging,
      magnetic resonance imaging (MRI) and cognitive tests; moreover all patients were
      submitted to preoperative, intraoperative and postoperative Transcranial Doppler
      (TCD) monitoring, in order to detect microembolic signals (MES). RESULTS:
      Mortality was zero; two patients developed myocardial infarction in the CEA group
      during follow-up. The main post-operative results after endarterectomy versus CAS
      were respectively: neurological deficit: 1.3% vs. 3.3%, embolic lesions at
      postoperative MRI: 4% vs. 34% and worsening of cognitive tests: 4% vs. 25.3%.
      CONCLUSION: CEA seems to be the treatment of choice for carotid stenosis, due to
      its low rate of mortality and morbidity, especially in asymptomatic patients; CAS
      should be carried out only in particular subgroup of cases, such as: restenosis,
      previous neck surgery or radian therapy, anatomical high bifurcation or extended
      lesions. Ongoing multicenter randomized trials may give a definitive answer to
      this matter.

PMID- 22990504
TI  - Factors related to long-term prognosis in medically treated type B aortic
      dissection: a physical predisposing factor.
AB  - AIM: In medically treated patients with Stanford type B aortic dissection, it has
      been shown that the state of the dissecting aorta in the acute phase predicts the
      prognosis. The present study examined other crucial factors, including physical
      characteristics, related to the long-term prognosis in type B aortic dissection.
      METHODS: Two hundred and two patients with type B aortic dissection who were
      discharged alive with medical treatment in the acute phase (mean age 66.5 years,
      range 29-90 years, 160 males) were followed. RESULTS: During the mean follow-up
      period of 4.9 years (ranging up to 12.2 years), 37 all-cause deaths were
      confirmed. A surgical procedure related to aortic dissection was performed in 8,
      and re-dissection occurred in 3. The survival rate at 5 years after onset was
      82%. On Cox regression analysis, increased height (greater than the median value)
      was significantly associated with all-cause death and the composite aortic event
      when adjusted by age and sex (hazard ratio [HR]=2.22, 95%confidence interval [CI]
      1.15-4.83, P=0.021, and HR=4.53, 95%CI 1.26-16.35, P=0.021, respectively).
      Patients with coexisting true aortic aneurysms also had a higher risk than those
      without (composite aortic events, HR=3.63, 95%CI 1.41-9.35, P=0.008). CONCLUSION:
      More strict management in the chronic phase is needed in taller patients as well
      as patients with coexisting true aortic aneurysms. This common physical
      predisposing feature may also assist in making the decision for earlier surgical
      intervention to the affected aorta.

PMID- 22990505
TI  - Femoral artery pseudoaneurysms in intravenous drug users: a 12-year series.
AB  - AIM: Management of pseudoaneurysms in intravenous drug users poses many questions
      regarding need for revascularization and type of surgery. The aim of this study
      was to report on the frequency and management of femoral artery pseudoaneurysms
      in our department during the last twelve years. METHODS: Retrospective report on
      patients hospitalized in the Department of Vascular Surgery in Red Cross
      Hospital, Athens, Greece between January 1999 and May 2010 with femoral artery
      pseudoaneurysms due to intravenous drug abuse. RESULTS: Overall, 23 patients (18
      men, 5 women, mean age 36 years) were identified. Of these, 20 patients underwent
      revascularization, while femoral artery ligation had to be performed in 3.
      Intraoperative evaluation of leg perfusion was decisive in choice of treatment.
      No patient presented with critical limb ischemia postoperatively. No amputations
      or complications were noted during the follow-up. CONCLUSION: Treatment of common
      femoral artery pseudoaneurysms in drug abusers should be tailored to individual
      requirements. Bypass surgery is not always required, due to the pre-existing
      collateral network in many cases.

PMID- 22990506
TI  - Surgery for ruptured abdominal aortic aneurysm and early mortality in women. Risk
      factors and complication profile.
AB  - AIM: Repair of ruptured abdominal aortic aneurysm (rAAA) is reported to have a
      higher mortality in women than in men. The aim was to study whether this
      difference could be verified in our institution and secondary if difference in
      risk- and complication profiles could explain the higher 30 day mortality after
      surgery for rAAA in women. METHODS: During the period 1983-2009 1649 patients,
      1348 men and 301 women, were operated consecutively for infrarenal abdominal
      aortic aneurysm (AAA); 430 patients had rAAA, 98 women and 332 men. Co
      morbidities were identified from the patients' medical records. Outcome measures
      within 30 days were mortality, cardiac disease (heart attack, heart failure),
      cerebrovascular disease (stroke, TIA), renal insufficiency (serum creatinine >140
      umol/L), major amputation, bowel infarction, pancreatitis and graft related
      complications. RESULTS: Compared to men, women had higher 30 d mortality after
      surgery for rAAA (54.1% vs. 36.3%, P=0.002). Women were significantly older than
      men (76 years vs. 73 years, P=0.001). In the period 1995-2009 women had more
      autoimmune diseases than men (P=0.045). There was no significant difference
      between men and women for the other measured outcomes. CONCLUSION: During the
      period 1995-2009, autoimmune disease were more common among women than men. For
      all other parameters recorded, there were no differences in risk - or
      complication profile that could explain the higher 30 d mortality in female
      patients after surgery for rAAA.

PMID- 22990507
TI  - Peripheral arterial disease in patients with chronic obstructive pulmonary
      disease.
AB  - AIM: Cardiovascular disease (CV) is the second leading cause of morbidity and
      mortality in chronic obstructive pulmonary disease (COPD). Peripheral arterial
      disease (PAD) is associated with cardiovascular disease, and its risk factors are
      common to other atherosclerotic diseases. The objective is to determine the
      prevalence of PAD in a population of patients with COPD using the ankle /
      brachial index (ABI) and to investigate the relationship between PAD and lung
      disease severity. METHODS: In a prospective cross-sectional study, 246 patients
      with COPD were recruited. Patients were enrolled consecutively according to their
      admission to Povisa hospital from September 1, 2008, until March 1, 2010, and
      were assessed by clinical history, spirometry and ABI. The COPD severity was
      graded by GOLD criteria in spirometry. RESULTS: Overall, 84 patients (36.8%) had
      abnormal ABI results and 59 (70.2%) were asymptomatic for PAD. COPD patients with
      PAD had a higher prevalence of moderate to severe COPD (61.9% vs. 41.7%,
      P=0.004), lower mean forced expiratory volume in 1 second (FEV1) values (46.7% +/
      15 vs. 52.3+/-14%, P=0.001) and a higher prevalence of hypertension (69% vs.
      54.3%, P=0.03) and previous cardiovascular disease (34.5% vs. 21.3%, P=0.03).
      CONCLUSION: There was a high prevalence of asymptomatic PAD in the COPD patients
      we examined. Abnormal ABI results were associated with a higher prevalence of
      cardiovascular risk factors and more severe lung disease. The diagnosis of
      peripheral arterial disease in COPD is important because this is an entity that
      limits the patient's physical activity and impairs their quality of life in
      addition to turn it into a high cardiovascular risk patient that requiring
      additional therapeutic measures.

PMID- 22990508
TI  - Low frequency of a decreased ankle brachial index and associated conditions in
      the practice of internal medicine in a Turkish population sample.
AB  - AIM: Peripheral arterial disease (PAD) is a less known condition in the practice
      of internal medicine, mostly due to lack of specific symptoms and low rates of
      physician awareness. However, cardiovascular disease (CVD) incidence is not
      significantly different among patients with symptomatic or asymptomatic disease.
      Ankle brachial index (ABI) measurement is an easy and cost-effective tool for the
      diagnosis of PAD. In the present study, frequency of low ABI and associated
      factors were investigated in the setting of internal medicine practice. METHODS:
      Patients over 70 years of age and patients between 50 and 69 years with CVD or at
      least one atherothrombosis risk factor were included in the study. ABI was
      determined with handheld Doppler. Measurements were determined for both lower
      extremities. Lower of the right or left ABIs was taken as the final value. Low
      ABI was defined as <=0.9. RESULTS: A total of 303 subjects between 50 and 83
      years of age were enrolled (female/male: 186/117). Mean ABI was 1.14+/-0.15. A
      low ABI was detected in 15 cases (4.95%). Prevalence was 7% in females and 1.7%
      in males (P=0.039). Low ABI value was not associated with any of the demographic
      parameters, presence of major risk factors or basic laboratory values. A high ABI
      was found by 5.6%. CONCLUSION: In the present study, frequency of PAD as
      determined by ABI was found lower than those reported previously in most European
      countries. Nonetheless, our results showed that PAD affects at least 1 in 20
      outpatients in the practice of internal medicine.

PMID- 22990509
TI  - Eligibility of patients with peripheral arterial disease for participation in a
      community-based walking exercise program: a single-centre experience.
AB  - AIM: Eligibility of patients with peripheral arterial disease (PAD) for exercise
      therapy is the most important requirement for predicting their training group
      adherence. METHODS: In this prospective, exploratory study over a period of 1
      year, a total of 462 PAD patients of an angiological outpatient routine care
      setting were consecutively recruited to the study. As non-eligibility criteria
      for exercise therapy were defined: resting pain or gangrene (Fontaine stage III
      and IV PAD), the inability to complete treadmill exercise, or premature treadmill
      discontinuation due to non-vascular walking pain. Also, PAD patients without
      subjective walking limitation (Fontaine stage I PAD) were assessed as unwilling,
      i.e. non-eligible for exercise training adherence. Criterion for patients
      eligibility was the occurrence of intermittent claudication on treadmill test
      (Fontaine stage II PAD). RESULTS: A total of 346 patients (age median 71 years,
      males 58.5%) were candidates for conservative therapy. Of them, 166 subjects
      (48%) were assessed as eligible for participation in walking exercise program.
      180 of the patients (52%) were deemed as non-eligible to perform walking exercise
      therapy. 115 patients (33%) were physically limited by critical limb ischemia
      (Fontaine stage III and IV PAD), severe comorbid cardiovascular disease or
      orthopaedic disorder. In 65 PAD patients (19%) the subjective walking capacity
      was not restricted. Social, logistical or other factors were found in 27 patients
      (8%) to be barriers for exercise training commencement. CONCLUSION: In half of
      the PAD patients whose attendance in a community-based walking exercise program
      would be a therapeutically reasonable activity, a range of vascular and non
      vascular factors are obstacles for participation. Further research is needed to
      investigate what measures might enhance the proportion of exercise therapy
      participants.

PMID- 22990510
TI  - Pilot trial of motivational interviewing in patients with peripheral artery
      disease.
AB  - AIM: Peripheral artery disease (PAD) is a common cause of impaired quality of
      life and reduced life expectancy in older adults. An important component of PAD
      management is improvement in health behavior, but few effective means to achieve
      this have been identified. The aim of the present study was to assess the
      efficacy of motivational interviewing (MI) to facilitate positive health behavior
      change in patients with PAD. METHODS: Participants (N.=23) diagnosed with PAD
      were randomized to MI sessions or a control group. Primary outcomes of physical
      activity and dietary behavior and secondary outcomes of quality of life were
      assessed with questionnaires at baseline and after 12 weeks. RESULTS: At 12
      weeks, physical activity (330 vs. 396 met-mins/week, P=0.74) and dietary behavior
      (1 vs. 1, P=0.89; 2.67 vs. 2.61, P=0.62) were similar in both groups. MI
      participants reported significantly better quality of life compared to control
      participants (71 vs. 61, P=0.01). Participants' comments suggested that MI
      promoted a process of re-appraisal of health status. CONCLUSION: This exploratory
      study has indicated that MI may improve aspects of quality of life and provide a
      prompt to reappraise health status and health behaviors in patients with PAD.
      Validation of these findings and assessment of impact on health outcomes is
      required in a larger and long-term study.

PMID- 22990511
TI  - Skin own bacteria may aggravate inflammatory and occlusive changes in
      atherosclerotic arteries of lower limbs.
AB  - AIM: Seroepidemiological studies have given rise to the hypothesis that
      microorganisms like Chlamydia pneumoniae (CP), Helicobacter pylori (HP),
      cytomegalovirus (CMV), HCV types 1 and 2, and bacteria involved in dental or
      other unspecified infection sites may initiate or maintain the atherosclerotic
      process in lower limb arteries. However, not much attention has been attached to
      the patient's own limb skin and deep tissues bacterial flora, activated in
      ischemic tissues. This flora may enhance the inflammatory and thrombotic process
      in the atherosclerotic arteries. Lower limb tissues are exposed to microorganisms
      from the environment (foot) and microbes on floating epidermal cells from the
      perineal and anal regions. The aim of this paper was to identify microbial cells
      and their DNA in perivascular tissues and arterial walls of lower limbs. METHODS:
      Bacterial cultures and PCR method for detection of 16sRNA and
      immunohistopathological staining for identification of immune cells infiltrating
      vascular bundles. RESULTS: 1) specimens of atherosclerotic calf and femoral
      arteries contained bacterial isolates and/or their DNA, whereas, in control
      normal cadaveric organ donors' limb arteries or patients' carotid arteries and
      aorta bacteria they were detected only sporadically; 2) lower limb lymphatics
      contained bacterial cells in 76% of specimens, whereas controls only in 10%; 3)
      isolates from limb arteries and lymphatics belonged in majority to the coagulase
      negative staphylococci and S.aureus, however, other highly pathogenic strains
      were also detected; 4) immunohistopathological evaluation arterial walls showed
      dense focal infiltrates of granulocytes and macrophages. CONCLUSION: Own
      bacterial isolates can be responsible for dense neutrophil and macrophage
      inflitrates of atherosclerotic walls and periarterial tissue in lower limbs and
      aggravate the ischemic changes.

PMID- 22990512
TI  - What is the correct distance measurement metric when measuring carotid ultrasound
      intima-media thickness automatically?
AB  - AIM: The aims of this study were: 1) to analyze the interobserver carotid intima
      media thickness (CIMT) variability using three different measurement metrics on
      large multi-institutional databases; 2) to evaluate the three kinds of metrics
      when comparing completely automated CIMT measurement (Auto Edge CIMT) to two
      manually derived CIMT (manual CIMT). METHODS: Two expert sonographers manually
      analyzed 665 carotid B-Mode ultrasound images collected from five institutions
      and using four different scanners. The two readers traced the lumen-intima (LI)
      and media-adventitia (MA) interfaces. The manual CIMT was computed from the LI/MA
      tracings by using three different distance measurement metrics: the Hausdorff,
      the PolyLine, and the Centerline distance metrics. The LI/MA tracings of a
      completely automated method we previously developed were then compared to manual
      CIMT. RESULTS: The average CIMT values of Readers 1 and 2 were 1.904+/-0.650 mm
      and 1.421+/-0.394 using Hausdorff, 0.808+/-0.269 mm and 0.790+/-0.227 mm using
      Polyline, and 0.762+/-0.266 mm and 0.782+/-0.228 mm using Centerline,
      respectively. The correlation coefficients were 0.14 (0.07-0.22) for Hausdorff,
      0.77 (0.74-0.80) for Polyline, and 0.82 (0.79-0.84) for Centerline. The variation
      coefficients (CV) were equal to 46.4% (Hausdorff), 2.6 % (Polyline), and 14.1%
      (Centerline). The Auto Edge CIMT values were: 1.655+/-0.676 mm using Hausdorff,
      0.808+/-0.282 mm using Polyline, and 0.776+/-0.275 mm using Centerline.
      CONCLUSION: Centerline and Polyline yield very close results and are clinically
      suitable distance measurement techniques for computing the CIMT from LI/MA
      profiles.

PMID- 22990513
TI  - Compression stockings have a synergistic effect with walking in the late
      afternoon to reduce edema of the lower limbs.
AB  - AIM: The aim of this study was to evaluate whether an association of elastic
      stockings and walking for a short period in the late afternoon reduces leg edema.
      METHODS: Volume changes of the legs of sixteen patients (32 limbs), who walked on
      a treadmill for 30 minutes using elastic compression stockings, were analyzed in
      a quantitative, cross-over randomized (in order of arrival at the clinic) study.
      They were submitted to volumetry using the water displacement technique and
      subsequently required to put on 20/30 made-to-measure compression stockings
      (Sigvaris). The patients walked on a treadmill for 30 minutes and after removing
      the stockings volumetry of the legs was again performed. Legs were assessed using
      the CEAP classification and divided into groups. Analysis of variance was used
      for statistical analysis with an alpha error of 5% being considered acceptable.
      RESULTS: When participants walked wearing compression stockings, there was a
      reduction in leg volume. When the CEAP classification was evaluated, it was noted
      that there was a statistically significant difference for the CEAP C0, C1 and C2
      categories of legs using stockings compared to those that did not use.
      CONCLUSION: Compression stockings have a synergistic effect with walking in the
      late afternoon thus reducing edema of the lower limbs.

PMID- 22990514
TI  - Intensive outpatient treatment of elephantiasis.
AB  - AIM: The aim of this paper was to report on a novel approach to the intensive
      outpatient treatment of elephantiasis of an underprivileged population. METHODS:
      Prospective, random study, the diagnosis of lymphedema was clinical and the
      inclusion of patients was by order of arrival in the treatment center where all
      were invited to participate in the study. Intensive outpatient therapy was
      performed for 6 to 8 hours daily over a period of four weeks. Eleven legs with
      grade III elephantiasis of 8 patients were evaluated in a random prospective
      study. Three patients were men and five were women with ages ranging between 28
      and 66 years old. Treatment included mechanical lymph drainage using the
      RAGodoy(r) apparatus for a period of 6 to 8 hours daily and the Godoy & Godoy
      cervical stimulation technique for 20 minutes per day, both associated to the use
      of a home-made medical compression stocking using a low-stretch cotton-polyester
      material. Additionally, manual lymph drainage using the Godoy & Godoy technique
      was performed for one hour. Perimetry was used to compare measurements made
      before and after treatment, of the three points of the limb with the largest
      circumferences. The paired t-test was utilized for statistical analysis with an
      alpha error greater than 5% (P-value <0.05). RESULTS: Reductions in the perimeter
      of affected limbs were significant over this 4-week treatment program (P
      value=0.001). CONCLUSION: Intensive outpatient treatment is an option for all
      types of lymphedema with large volumetric reductions being possible in a short
      period when treating elephantiasis.

PMID- 22990516
TI  - Diagnostic delay for endometriosis in Austria and Germany: causes and possible
      consequences.
AB  - STUDY QUESTION: What is the length of the diagnostic delay for endometriosis in
      Austria and Germany, and what are the reasons for the delay? SUMMARY ANSWER: The
      diagnostic delay for endometriosis in Austria and Germany is surprisingly long,
      due to both medical and psychosocial reasons. WHAT IS KNOWN ALREADY: Diagnostic
      delay of endometriosis is a problematic phenomenon which has been evaluated in
      several European countries and in the USA, but has not been reported for Germany
      and Austria. STUDY DESIGN, SIZE, DURATION: A cross-sectional, questionnaire-based
      multicentre study was conducted in tertiary referral centers in Austria and
      Germany. From September 2010 to February 2012, 171 patients with histologically
      confirmed endometriosis were included. PARTICIPANTS, SETTING, METHODS: Patients
      with a previous history of surgically proven endometriosis, internal diseases
      such as rheumatic disorders, pain symptoms of other origin, gynecological
      malignancy or post-menopausal status were excluded from the analysis. Patients
      with histologically confirmed endometriosis completed a questionnaire about their
      psychosocial and clinical characteristics and experiences. Of 173 patients, two
      did not provide informed consent and were excluded from the study. MAIN RESULTS
      AND THE ROLE OF CHANCE: The median interval from the first onset of symptoms to
      diagnosis was 10.4 (SD: 7.9) years, and 74% of patients received at least one
      false diagnosis. Factors such as misdiagnosis, mothers considering menstruation
      as a negative event and normalization of dysmenorrhea by patients significantly
      prolonged the diagnostic delay. No association was found between either
      superficial and deep infiltrating endometriosis or oral contraceptive use and the
      prolongation of diagnosis. LIMITATIONS AND REASONS FOR CAUTION: There was a
      possible selection bias due to inclusion of surgically treated patients only.
      WIDER IMPLICATIONS OF THE FINDINGS: Several factors causing prolongation of
      diagnosis of endometriosis have been reported to date. The principal factors
      observed in the present study are false diagnosis and normalization of symptoms.
      Teaching programs for doctors and public awareness campaigns might reduce
      diagnostic delay in Central Europe. STUDY FUNDING/COMPETING INTEREST(S): No
      competing interests exist.

PMID- 22990515
TI  - Single embryo transfer reduces the risk of perinatal mortality, a population
      study.
AB  - STUDY QUESTION: Do births following single embryo transfers (SET) have a reduced
      risk of perinatal mortality compared with those following double embryo transfers
      (DET)? SUMMARY ANSWER: SET is associated with reduced risk of perinatal mortality
      compared with DET. WHAT IS KNOWN ALREADY: Fetal, neonatal and perinatal mortality
      are important indicators for monitoring pregnancy and childbirth, particularly
      for births following assisted reproductive technology (ART) treatments. Following
      the introduction of SET, there has been a decline in the perinatal mortality rate
      (PMR) among babies born after ART in Australia and New Zealand. STUDY DESIGN,
      SIZE, DURATION: This population study (census) included 50,258 births of >= 20
      weeks gestation and/or >= 400 g of birthweight following embryos transfer cycles
      in Australia and New Zealand during the period 2004-2008. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: The PMR was calculated according to the number of embryos
      transferred and other demographic and treatment-related factors. Perinatal deaths
      were defined as the number of fetal deaths (stillbirths) plus the number of
      neonatal deaths (deaths that occur before 28 days after birth). MAIN RESULTS AND
      THE ROLE OF CHANCE: The PMR was 16.2 per 1000 births (n= 813). Of the 813
      perinatal deaths, 630 were fetal deaths and 183 neonatal deaths. Twins had a
      significantly higher PMR (27.8 per 1000 births) than singletons (12.4 per 1000
      births). The risk of perinatal mortality for all births following DET was 53%
      higher than for all births following SET (adjusted risk ratio 1.53, 95%
      confidence interval (95% CI): 1.29-1.80). Births following fresh DET had a 58%
      increased risk of perinatal mortality compared with births following fresh SET
      (risk ratio 1.58, 95% CI: 1.32-1.90). LIMITATIONS, REASONS FOR CAUTION:
      Information on outcomes was missing from <1% of clinical pregnancies recorded in
      Australian and New Zealand Assisted Reproduction Database for the study period.
      There are no data on the timing of fetal death, the cause of perinatal death or
      on late termination of pregnancy at >= 20 weeks' gestation. WIDER IMPLICATIONS OF
      THE FINDINGS: Double and higher order embryo transfer is associated with a higher
      risk of perinatal mortality when compared with SET. The number of embryos
      transferred is determined by the clinician with consent of the patient and is a
      modifiable treatment factor. SET should be advocated as the first-line management
      in ART as it is the single most effective public health intervention for
      preventing excess perinatal mortality among ART pregnancies. STUDY
      FUNDING/COMPETING INTEREST(S): Nil.

PMID- 22990517
TI  - Infrahyoid myocutaneous flap for medium-sized head and neck defects: surgical
      outcome and technique modification.
AB  - OBJECTIVES: To evaluate the surgical outcomes associated with infrahyoid
      myocutaneous flaps used in the reconstruction of medium-sized defects following
      head and neck cancer resection, as well as to discuss a novel technique
      modification. STUDY DESIGN: Case series with chart review. SETTING: University
      cancer hospital. SUBJECTS AND METHODS: A total of 20 patients with oral or
      hypopharyngeal carcinoma who underwent infrahyoid myocutaneous flap
      reconstruction between June 2005 and December 2011 were retrospectively studied.
      A novel technical modification of flap harvest, preservation of the cranial
      portion of the anterior jugular vein, was attempted in 15 flaps and was
      successful in 13 flaps. Functional evaluation was performed in all patients 3 to
      6 months after the operation or postoperative radiation. RESULTS: Total flap
      necrosis, marginal skin paddle necrosis, and total skin paddle loss were observed
      in 1, 2, and 1 patient(s), respectively. Pharyngocutaneous fistula without flap
      problem occurred in 1 patient. No flap complications occurred in 13 cases where
      the cranial portion of the anterior jugular vein was successfully preserved.
      Functional results were excellent in 16 patients, good in 3 patients, and fair in
      1 patient. CONCLUSION: The infrahyoid myocutaneous flap is a reliable and
      convenient technique that can serve as an alternative to free flaps in the
      reconstruction of medium-sized defects of the oral cavity or hypopharynx.
      Preservation of the cranial portion of the anterior jugular vein is a novel
      technical modification of harvesting this flap, which may result in better venous
      return of the skin paddle and reduce skin paddle necrosis.

PMID- 22990518
TI  - Clinical consensus statement: tracheostomy care.
AB  - OBJECTIVE: This clinical consensus statement (CCS) aims to improve care for
      pediatric and adult patients with a tracheostomy tube. Approaches to tracheostomy
      care are currently inconsistent among clinicians and between different
      institutions. The goal is to reduce variations in practice when managing patients
      with a tracheostomy to minimize complications. METHODS: A formal literature
      search was conducted to identify evidence gaps and refine the scope of this
      consensus statement. The modified Delphi method was used to refine expert opinion
      and facilitate a consensus position. Panel members were asked to complete 2 scale
      based surveys addressing different aspects of pediatric and adult tracheostomy
      care. Each survey was followed by a conference call during which results were
      presented and statements discussed. RESULTS: The panel achieved consensus on 77
      statements; another 39 were dropped because of lack of consensus. Consensus was
      reached on statements that address initial tracheostomy tube change, management
      of emergencies and complications, prerequisites for decannulation, management of
      tube cuffs and communication devices, and specific patient and caregiver
      education needs. CONCLUSION: The consensus panel agreed on statements that
      address the continuum of care, from initial tube management to complications in
      children and adults with a tracheostomy. The panel also highlighted areas where
      consensus could not be reached and where more research is needed. This consensus
      statement should be used by physicians, nurses, and other stakeholders caring for
      patients with a tracheostomy.

PMID- 22990519
TI  - Double-outlet left ventricle with L-malposition of the great arteries and
      subpulmonary ventricular septal defect.
AB  - Double-outlet left ventricle is a very rare congenital cardiac anomaly with
      various anatomic types. This report describes an infant with the aorta anterior
      and to the left of the pulmonary trunk, a subpulmonary ventricular septal defect,
      and pulmonary artery stenosis. This variation has not been described to date in
      patients with a double-outlet left ventricle.

PMID- 22990520
TI  - Response of peripheral blood Th17 cells to inhaled Dermatophagoides pteronyssinus
      in patients with allergic rhinitis and asthma.
AB  - BACKGROUND: Recent studies have shown the importance of Th17 cells in the
      development of allergic airway diseases. We examined Dermatophagoides
      pteronyssinus-induced changes in peripheral blood Th17 cells to establish the
      importance of these cells in late-phase allergic inflammation in patients with
      allergic rhinitis (AR) and allergic asthma (AA). METHODS: Eighteen patients with
      mild-to-moderate/severe persistent AR, 14 patients with intermittent- or mild-to
      moderate persistent AA, and 15 healthy subjects (HS) were examined. All patients
      had positive skin test to D. pteronyssinus. Study subjects underwent bronchial
      challenge with D. pteronyssinus. The peripheral blood Th1, Th2, and Th17 cells
      were determined by flow cytometry 24 h before and 7 and 24 h after challenge. The
      serum IL-17 levels were determined by ELISA. RESULTS: The percentage of Th17
      cells and IL-17 levels was significantly higher in patients with AR and AA
      compared with HS before and after challenge. Twenty-four hours after challenge,
      the percentage of Th17 cells increased significantly in patients with AA compared
      with baseline values. The IL-17 levels rose markedly in patients with AR and AA
      after challenge. Moreover, 24 h after challenge, the percentage of Th17 cells and
      IL-17 levels were significantly higher in patients with AA than those with AR.
      CONCLUSIONS: Percentages of peripheral blood Th17 cells and serum IL-17 levels
      were found to be higher in patients with AR and AA. An increase in the percentage
      of Th17 cells following challenge shows that Th17 cells may have an important
      role in the development of late-phase allergen-induced inflammation.

PMID- 22990523
TI  - Local aromaticity of the five-membered rings in acenaphthylene derivatives.
AB  - In this paper, a detailed study of the local aromaticity in a series of
      cyclopenta-fused linear polyacenes (acenaphthylene derivatives) was performed
      using several different criteria of aromaticity. Namely, the energy effect (ef),
      bond resonance energy (BRE), harmonic oscillator model of aromaticity (HOMA)
      index, multi centre delocalization indices (MCI), electron density at ring
      critical points rho(r(C)), nucleus independent chemical shifts (NICS) and ring
      current maps were employed. All these methods agree that the extent of
      aromaticity of the five-membered ring in the acenaphthylene molecule is quite
      small. On the other hand, it was shown that the aromatic character of the five
      membered rings depends on the size of the polyacenic part and on the position of
      the five-membered ring along the polyacenic part of the given acenaphthylene
      derivatives. According to energetic, electron delocalization and geometrical
      indices, the aromatic character of the pentagons in some higher acenaphthylene
      congeners is of the same order of magnitude as the aromatic character of some
      hexagons in the respective molecules. Ring current maps revealed the existence of
      a weak paratropic (antiaromatic) circulation in the five-membered rings which, in
      the case of higher members of the homolog series, becomes weaker. In contrast,
      the NICS indices showed a significant antiaromatic character of the five-membered
      rings in higher members of the acenaphthylene series.

PMID- 22990521
TI  - The nuclear envelope proteome differs notably between tissues.
AB  - One hypothesis to explain how mutations in the same nuclear envelope proteins
      yield pathologies focused in distinct tissues is that as yet unidentified tissue
      specific partners mediate the disease pathologies. The nuclear envelope proteome
      was recently determined from leukocytes and muscle. Here the same methodology is
      applied to liver and a direct comparison of the liver, muscle and leukocyte data
      sets is presented. At least 74 novel transmembrane proteins identified in these
      studies have been directly confirmed at the nuclear envelope. Within this set, RT
      PCR, western blot and staining of tissue cryosections confirms that the protein
      complement of the nuclear envelope is clearly distinct from one tissue to
      another. Bioinformatics reveals similar divergence between tissues across the
      larger data sets. For proteins acting in complexes according to interactome data,
      the whole complex often exhibited the same tissue-specificity. Other tissue
      specific nuclear envelope proteins identified were known proteins with functions
      in signaling and gene regulation. The high tissue specificity in the nuclear
      envelope likely underlies the complex disease pathologies and argues that all
      organelle proteomes warrant re-examination in multiple tissues.

PMID- 22990525
TI  - Hemodynamic and biochemical benefits of the objective measurement of fluid status
      in hemodialysis patients.
AB  - Subtle fluid imbalance can cause poor clinical outcomes among hemodialysis
      patients.  However, the traditional subjective assessment of fluid status may be
      inadequate.  We evaluated whether the objective measurement and optimization of
      fluid status could be beneficial for hemodynamic and biochemical parameters in
      hemodialysis patients.  We enrolled 120 hemodialysis patients, who were
      clinically euvolemic for at least 3 months.  Based on the results of a body
      composition monitor, we divided the patients into the following two groups: the
      hyperhydrated group (post hemodialysis fluid overload >= 1.1 L) and the
      dehydrated group (post hemodialysis fluid overload < -1.1 L).  We reduced the
      patient's body weight in the hyperhydrated group and raised the body weight in
      the dehydrated group towards normohydration (-1.1 L <= fluid overload < 1.1 L)
      for 16 weeks.  Forty-four of 120 patients were in the hyperhydrated group, and 18
      of 120 patients in the dehydrated group.  After 16 weeks, systolic blood pressure
      and pulse pressure decreased in the hyperhydrated group, while there was no
      increase in blood pressure in the dehydrated group after the intervention.  Serum
      levels of monocyte chemotactic protein-1, an inflammatory marker, gradually
      decreased in the hyperhydrated group, and serum adiponectin levels, an anti
      atherogenic biomarker, increased in the two groups.  We found that hyperhydrated
      patients contributed over 1/3 of the participants despite enrolling clinically
      euvolemic patients and that body composition monitor-guided optimization of body
      fluid status may lead to improvement of inflammatory markers and anti-atherogenic
      adipokines as well as hemodynamic parameters in hemodialysis patients.

PMID- 22990522
TI  - Nucleosome spacing and chromatin higher-order folding.
AB  - Packing of about two meters of the human genome DNA into chromatin occupying a
      several micron-sized cell nucleus requires a high degree of compaction in a
      manner that allows the information encoded on DNA to remain easily accessible.
      This packing is mediated by repeated coiling of DNA double helix around histones
      to form nucleosome arrays that are further folded into higher-order structures.
      Relatively straight DNA linkers separate the nucleosomes and the spacing between
      consecutive nucleosome varies between different cells and between different
      chromosomal loci. In a recent work ( 1)  our group used a biochemically defined
      in vitro reconstituted system to explore how do various DNA linkers mediate
      nucleosome array packing into higher-order chromatin structures. For long
      nucleosome linkers (about 60 bp) we observed a more open chromatin structure and
      no effect of small linker length alterations (+/-2-4 bp) on chromatin folding. In
      striking contrast, for shorter linkers (20-32 bp) we found more compact packing
      with strong periodical dependence upon the linker DNA lengths. Our data together
      with high-resolution nucleosome position mapping provide evidence for the natural
      nucleosome repeats to support a chromatin architecture that, by default,
      restricts spontaneous folding of nucleosome arrays into compact chromatin fibers.
      We suggest that incomplete folding of the nucleosome arrays may promote global
      inter-array interactions that lead to chromatin condensation in metaphase
      chromosomes and heterochromatin.

PMID- 22990526
TI  - Hyperventilation accelerates rise in arterial blood concentrations of sevoflurane
      in gynecologic patients.
AB  - PURPOSE: We investigated whether ventilation volumes affected arterial blood
      sevoflurane concentration (A (sev)) and its uptake into the body during general
      anesthesia. METHODS: Thirty female patients undergoing elective gynecologic
      surgery were randomly allocated into three groups: hyperventilation, normal
      ventilation, and hypoventilation. Inspiratory (CI(sev)) and end-tidal ((sev))
      sevoflurane concentrations were routinely measured by infrared analysis, and A
      (sev) were analyzed by gas chromatography for 40 min after intubation. Cardiac
      index and total peripheral vascular resistance were measured with a Finometer.
      RESULTS: During the first 10 min after sevoflurane administration, A (sev) in the
      hyperventilation group was the highest and differed significantly from those in
      the normal ventilation group, followed by those in the hypoventilation group. In
      addition, hyperventilation significantly increased the slope of A (sev) over time
      in the first 5 min, but there were no differences in slopes in the 5-10, 10-20,
      and 20-40 min periods, which indicates no difference in sevoflurane bodily uptake
      among the three groups after 5 min. CONCLUSION: Hyperventilation accelerated the
      rate of A (sev) increase immediately after sevoflurane administration, which was
      time dependent with respect to different alveolar ventilation levels.

PMID- 22990528
TI  - Performance of a Parker Flex-Tip tube((r)) for intubation with the Pentax
      AirwayScope((r)).

PMID- 22990527
TI  - Neurolytic celiac plexus block reduces occurrence and duration of terminal
      delirium in patients with pancreatic cancer.
AB  - PURPOSE: WHO's three step ladder sometimes cannot provide adequate pain relief
      for pancreatic cancer. Some patients develop terminal delirium (TD). The aim of
      this study was to test if the addition of a celiac plexus block (CPB) to
      pharmacotherapy could reduce the incidence of TD. METHODS: Pancreatic cancer
      patients under the care of our palliative-care team were investigated with regard
      to the duration and occurrence of TD, pain scores [numerical rating score (NRS)]
      and daily opioid dose. Between August 2007 to September 2008, 17 patients
      received only pharmacotherapy (control group). Then, we modified our guideline
      for analgesia, performing CPB 7 days after the first intervention of our team.
      Between October 2008 to September 2009, 19 patients received CPB. RESULTS: The
      opioid doses in CPB group were significantly lower both at 10 days after the
      first intervention (3 days after CPB) (27 +/- 11 vs. 66 +/- 82 mg; p = 0.029) and
      2 days before death (37 +/- 25 vs. 124 +/- 117 mg; p = 0.009). NRS in the CPB
      group were significantly lower both at 10 days after the first intervention (0 [0
      2] vs. 3 [2-5], p < 0.0001) and 2 days before death (1 [0-2] vs. 3 [1-4.5], p =
      0.018). The occurrence and duration of TD in CPB group were both reduced (42 vs.
      94 %, p = 0.019; and 1.8 +/- 2.9 vs. 10.4 +/- 7.5 days, p = 0.0003). CONCLUSION:
      The duration and occurrence of TD and the pain severity were significantly less
      in pancreatic cancer patients who underwent neurolytic CPB.

PMID- 22990530
TI  - Nanomaterials for renewable energy production and storage.
AB  - Over the past decades, there have been many projections on the future depletion
      of the fossil fuel reserves on earth as well as the rapid increase in green-house
      gas emissions. There is clearly an urgent need for the development of renewable
      energy technologies. On a different frontier, growth and manipulation of
      materials on the nanometer scale have progressed at a fast pace. Selected recent
      and significant advances in the development of nanomaterials for renewable energy
      applications are reviewed here, and special emphases are given to the studies of
      solar-driven photocatalytic hydrogen production, electricity generation with dye
      sensitized solar cells, solid-state hydrogen storage, and electric energy storage
      with lithium ion rechargeable batteries.

PMID- 22990529
TI  - Involvement of interleukin-17A in pancreatic damage in rat experimental acute
      necrotizing pancreatitis.
AB  - Interleukin (IL)-17A is a proinflammatory cytokine, which has recently attracted
      much interest due to its pathogenic role in various inflammatory conditions such
      as ischemia/reperfusion injury, chronic inflammation, and autoimmune diseases,
      but the role of IL-17A in acute pancreatitis remains unclear. This study aimed to
      investigate the role of IL-17A in experimental acute necrotizing pancreatitis
      (ANP). We analyzed the expression of IL-17A during the pathogenesis of ANP in
      vivo induced by 3 % sodium taurocholate (NaTc), by microarray test, quantitative
      real-time PCR, Western blotting, enzyme-linked immunosorbent assay, and
      immunohistochemistry. The effects of IL-17A on pancreatic acinar cells and
      pancreatic stellate cells (PSCs) were further investigated in vitro using
      recombinant rat IL-17A (rIL-17A). Expression of IL-17A was significantly
      increased following experimental acute pancreatitis. In addition, rIL-17A induced
      rat pancreatic acinar cell necrosis and promoted expression of several target
      genes, including IL-6, IL-1beta, CXCL1, CXCL2, and CXCL5, in acinar cells and
      PSCs. These findings suggest that IL-17A may be involved in pancreatic damage by
      regulating the expression of inflammatory cytokines and chemokines during
      experimental acute pancreatitis.

PMID- 22990532
TI  - Prognostic factors for melanoma progression and metastasis: from Hematoxylin
      Eosin to genetics.
AB  - Researchers have searched for factors that predict the metastatic potential of
      melanomas for decades. In recent years, the study of their metastatic potential
      has progressed from routine histological analysis of Hematoxylin-Eosin stained
      slides to proteomic, genetic, and molecular pathological analyses. As a result,
      knowledge about the metastatic potential of melanomas has progressed. Hundreds of
      prognostic factors have been described in literature and it is not possible to
      mention all of them in a report. Therefore, in the current report, we summarize
      some of them.

PMID- 22990531
TI  - Automatic 2D registration of renal perfusion image sequences by mutual
      information and adaptive prediction.
AB  - The objective of this study was to develop an automatic image registration
      technique capable of compensating for kidney motion in renal perfusion MRI, to
      assess the effect of renal artery stenosis on the kidney parenchyma. MATERIALS
      AND METHODS: Images from 20 patients scheduled for a renal perfusion study were
      acquired using a 1.5 T scanner. A free-breathing 3D-FSPGR sequence was used to
      acquire coronal views encompassing both kidneys following the infusion of Gd
      BOPTA. A two-step registration algorithm was developed, including a preliminary
      registration minimising the quadratic difference and a fine registration
      maximising the mutual information (MI) between consecutive image frames. The
      starting point for the MI-based registration procedure was provided by an
      adaptive predictor that was able to predict kidney motion using a respiratory
      movement model. The algorithm was validated against manual registration performed
      by an expert user. RESULTS: The mean distance between the automatically and
      manually defined contours was 2.95 +/- 0.81 mm, which was not significantly
      different from the interobserver variability of the manual registration procedure
      (2.86 +/- 0.80 mm, P = 0.80). The perfusion indices evaluated on the manually and
      automatically extracted perfusion curves were not significantly different.
      CONCLUSIONS: The developed method is able to automatically compensate for kidney
      motion in perfusion studies, which prevents the need for time-consuming manual
      image registration.

PMID- 22990533
TI  - Alzheimer's factors in postischemic dementia.
AB  - The way for explanation postischemic dementia processes has been one fraught with
      a wide range of complications and frequent revisions with a lack of a final clear
      solution. Data from animal models of brain ischemia and human ischemic brains
      studies have demonstrated an overexpression of amyloid precursor protein and
      increase production of a beta-amyloid peptide. Restoration brain activity
      following ischemic brain episode is delayed and not always complete due to an
      alteration related with increase in the level of the beta-amyloid peptide. In
      this paper, we will propose our idea about production of the beta-amyloid peptide
      from the amyloid precursor protein in ischemic brain lesions, and how this
      protein presents etiological and therapeutic targets that are now under
      consideration. Maturation of the ischemic brain tissue pathology may be caused
      not only by a neurodegeneration of selectively vulnerable neuronal cells
      destroyed following  ischemia but also by acute and chronic pathology of 
      resistant parts of the brain and chronic changes in the blood-brain barrier. We
      propose that in dementia following ischemia an initial ischemic episode precedes
      the brain tissue deposition of beta-amyloid peptide, which in turn amplifies the
      vascular dysfunction after first episode of ischemia triggering next focal
      ischemic episodes as vicious cycle preceding final ischemic degenerative changes
      and may gradually over a lifetime, progress to brain atrophy and finally to
      postischemic dementia with Alzheimer's phenotype.

PMID- 22990534
TI  - Schwann cell cultures: recent advances and novel approaches to the reconstruction
      of peripheral nerve defects.
AB  - Current techniques in tissue engineering may offer a choice regarding the
      reconstructive strategies of peripheral nerves. Schwann cell cultures are to be
      considered an appropriate option in the reconstruction of peripheral nerve and
      spinal cord large defects. Schwann cells availability from peripheral nerve
      autografts creates a great benefit concerning their usefulness in the nervous
      autogenic transplantation. Allogeneic Schwann cells transplantation can be
      effective in the reconstruction without delay of peripheral nerve defects.

PMID- 22990535
TI  - Arterial aging: a brief review.
AB  - Aging is associated with changes in arterial wall structure and function that
      exceed physiological adaptation, with an increased risk of cardiovascular events.
      The most consistent structural changes are luminal enlargement (dilatation), wall
      thickening (remodeling), and a reduction of elastic properties. Endothelial
      dysfunction plays an important role in the functional changes that occur with
      age. New target therapies to prevent or reverse this process are under
      evaluation.

PMID- 22990536
TI  - The immunohistochemical expression of endocrine gland-derived-VEGF (EG-VEGF) as a
      prognostic marker in ovarian cancer.
AB  - Ovarian cancer-related angiogenesis is a complex process orchestrated by many
      positive and negative regulators. Many growth factors are involved in the
      development of the tumor-associated vasculature, and from these, endocrine gland
      derived vascular endothelial growth factor (EG-VEGF) seems to play a crucial
      role. EG-VEGF is the first organ-specific angiogenic factor and its effects are
      restricted to the endothelial cells of the endocrine glands. Although EG-VEGF was
      detected in both normal and neoplastic ovaries, its clinical significance remains
      controversial. In the present study, we analyzed 30 patients with epithelial
      ovarian cancer, and the immunohistochemical expression of EG-VEGF was compared
      with the conventional clinico-pathological parameters of prognosis. Neoplastic
      cells of the ovarian carcinoma expressed EG-VEGF in 73.33% of the cases, as a
      cytoplasmic granular product of reaction. We found a strong correlation between
      the expression of EG-VEGF at protein level and tumor stage, grade, and
      microscopic type. The expression of EG-VEGF was found in patients with stage III
      and IV, but not in stage II. The majority of serous adenocarcinoma, half of the
      cases with clear cell carcinoma and two cases with endometrioid carcinoma showed
      definite expression in tumor cells. No positive reaction was found in the cases
      with mucinous carcinoma. Our results showed that EG-VEGF expression is an
      indicator not only of the advanced stage, but also of ovarian cancer progression.
      Based on these data, we concluded that EG-VEGF expression in tumor cells of the
      epithelial ovarian cancer is a good marker of unfavorable prognosis and could be
      an attractive therapeutic target in patients with advanced-stage tumors,
      refractory conventional chemotherapy.

PMID- 22990537
TI  - Relationship between immunohistochemical assessment of bronchial mucosa
      microvascularization and clinical stage in asthma.
AB  - Although hardly ever used in current practice, fibrobronchoscopy may provide
      interesting histopathological-clinical correlations in patients diagnosed with
      different stages of evolutive asthma. The aim of the study was to evaluate the
      correlation between semi-quantitative microvascularization features and the
      asthma severity assessed according to the GINA classification 2006. Our study
      group consisted in 21 patients diagnosed with asthma of different stages of
      severity and two-control patients investigated by fibrobronchoscopy with
      associated biopsy. The tissue fragments underwent standard processing procedures
      for the immunohistochemical exam, using CD34 as microvascularization marker. The
      semi-quantitative analysis was based on the "hot spot" method and on a score
      system that corresponds to the microvessels density. The statistical analysis of
      the correspondence between CD34 score and clinical parameters was performed using
      the SPSS 17 software, applying non-parametric correlation tests. The CD34
      evaluation showed an increase in blood vessels count in all asthmatic patients in
      comparison to the control group and a close correlation with the asthma severity,
      reflected by the FEV1 values. The statistical analysis showed an inverse
      correlation between FEV1 [%] values and CD34 expression (r=-0.93, p<<0.01). Our
      data concur to other research reports, supporting the hypothesis that
      angiogenesis initially facilitates the edema development and later on appears to
      be involved in the bronchial wall thickening, as a component of the chronic
      inflammatory response, with concomitant distensibility reduction. The bronchial
      mucosa microvascularization evaluation opens new perspectives for advanced
      therapies, with beneficial effects for asthmatic patients' life quality.

PMID- 22990538
TI  - The influence of diabetes mellitus on periodontal tissues: a histological study.
AB  - OBJECTIVE: The aim of this study was to investigate histological changes that
      occur in the periodontium of subjects with type 2 diabetes mellitus without signs
      of periodontal disease and to establish the influence of this systemic condition
      upon periodontal structures. MATERIALS AND METHODS: Gingival tissue samples were
      obtained from 12 adult patients with type 2 diabetes mellitus and 10 healthy
      adults, as control group. The specimens were examined using standard dyes as
      Hematoxylin and Eosin and PAS-Alcian stain, by a microscope with different
      magnifications. RESULTS: Our results showed that periodontal disease in patients
      with type 2 diabetes mellitus is characterized by significant inflammation,
      affecting both epithelial and connective tissues, with degeneration of dermal
      papilla, increase in number of inflammatory cells, destruction of reticular
      fibers and accumulation of dense collagen fibers (fibrosis). CONCLUSIONS: Within
      the limits of this study, diabetic subjects presented distortion in periodontal
      attachment, with changes in both epithelial and connective tissues, when compared
      to the healthy controls, suggesting that diabetes mellitus has an independent
      effect on periodontal tissue. This effect is observed in both groups, so that we
      considered it to be independent of the periodontal condition.

PMID- 22990540
TI  - Chronic bronchitis: a retrospective clinicopathologic study of 25 cases.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of
      morbidity and mortality in the industrialized and in the developing countries.
      Chronic bronchitis (CB) is one the three COPD clinico-pathological entities that
      in 2009 were estimated to be diagnosed in 9.9 million Americans. It is
      characterized by inflammation of the "bronchial tree" that results in tissue
      swelling and excessive secretions of mucus into the bronchi, with progressive
      airflow limitation. Our study aims to reveal the main morphological aspects of CB
      in our casuistry and to evaluate their correlation with major clinico
      epidemiological parameters. Thus, we performed a retrospective clinical and
      morphological study on a group of 17 smoker patients with symptoms of chronic
      bronchitis, eight non-smokers diagnosed with chronic bronchitis and five non
      smokers and asymptomatic subjects. We observed that CB developed especially in
      men of 65-year-old or older, especially in smokers with a median FEV1% at around
      71. Histopathologically, patients with symptoms of CB, regardless of smoking
      status, presented on bronchial biopsies with focal squamous metaplastic change,
      goblet cell hyperplasia and enlargement of the bronchial gland mass because of
      the inflammatory process, consisting predominantly of mononuclear cells in the
      bronchial wall. The statistical testing proved a significant correlation between
      the densities of different inflammatory cell classes (with the exception of mast
      cells in the bronchial epithelium) and FEV1% values on epithelium and submucosa
      regions in all investigated groups.

PMID- 22990541
TI  - Cytotoxic antibodies monitoring in kidney transplantation--their clinical
      relevance and challenges.
AB  - INTRODUCTION: The key of the successful renal transplantation is the ability to
      identify the best immunological match between donor and recipient considering the
      possibility of rejection phenomenon. The aim was to identify class I and/or class
      II cytotoxic antibodies in renal-transplanted patients in order to assess the
      immunological potential for prevention of subclinical or acute rejection
      episodes. PATIENTS AND METHODS: We have evaluated ninety-two patients who had
      kidney transplantation in 2010 in Fundeni Clinical Institute, Bucharest, Romania,
      concerning HLA matching and anti-HLA immunization status. For HLA genotyping were
      used molecular biology methods--PCR-SSP (Invitrogen, USA). For cytotoxic
      antibodies, the methods used were ELISA (GTI Diagnostics, USA) and Luminex (One
      Lambda, USA). Crossmatch tests between donor cells and recipient serum were
      performed by ELISA (GTI Diagnostics, USA). Rejection diagnosis was supported by
      renal biopsy. RESULTS: In the 20 presensitized cases, the rate of acute rejection
      was 30% while in the 72 unsensitized cases the rejection was 19.4%. The incidence
      of acute rejection was higher in anti-HLA class I presensitized patients compared
      with anti-HLA class II (20% and 14.3%, respectively) but there was no significant
      difference compared to pre-transplant unsensitized patients (19.4%). Sequential
      post-transplantation monitoring of anti-HLA antibodies has shown in pre
      transplant sensitized patients group a constantly increasing of PRA value, while
      in the pre-transplant unsensitized patients group, 32% developed de novo
      cytotoxic antibodies. CONCLUSIONS: More sensitive and specific methods to detect
      anti-HLA antibodies before transplantation and sequential post-transplantation
      monitoring of these antibodies would be useful to identify patients who are at
      higher risk for allograft failure.

PMID- 22990542
TI  - Ki67 and Bcl-2 immunoexpression in primitive urothelial bladder carcinoma.
AB  - Bladder cancer ranks among eight human malignant lesions, 90% being urothelial
      carcinomas. We evaluated the Ki67 and Bcl-2 immunoexpression and their
      correlations with clinicopathological parameters. The study included 45 primitive
      bladder urothelial carcinoma diagnosed in patients aged in VI and VII decades of
      life, predominantly in males. Histopathologically, the most numerous were
      moderately differentiated carcinomas (68.8%), most patients being classified in
      stage I of disease (48.8%). The analysis for Ki67 immunostain revealed positivity
      in 71.1% of cases, with higher values in moderate and poorly differentiated
      tumors in stage III or IV of disease. In contrast, immunoreactivity for Bcl-2 was
      present in 33.3% of well and moderately differentiated analyzed tumors and
      classified in stage I and II of disease. Tumor stage and grade is not correlated
      with Bcl-2 but there was a strong correlation with Ki67 proliferation index. Ki67
      immunoexpression may be helpful to identify patients at high risk who may benefit
      by adjuvant therapies.

PMID- 22990543
TI  - The heterogeneity of craniofacial morphology in Prader-Willi patients.
AB  - Prader-Willi syndrome is a complex genetic disorder with narrow spectrum of
      facial phenotypic signs, which make the clinical diagnosis difficult in some
      cases. There are several reports describing the craniofacial appearance of Prader
      Willi patients, but there are only a few cephalometric studies for these
      patients. In this study were included 18 patients with Prader-Willi syndrome and
      a control group of 18 subjects of both sexes selected based on specific criteria.
      The cephalometric radiographs of the patients were taken using the standardized
      technique with centric teeth in occlusion and lips in relaxed position. Angular,
      horizontal and linear measurements were analyzed for the study group and for the
      control group. We established that in Prader-Willi patients, there is a decrease
      of the majority of parameters but the degree of this reduction varies widely
      between patients and clinically typical facies not always have smaller
      measurements which can be found in an unusual facies. Facial dysmorphism in
      Prader-Willi patients varies a group ranging from miss proportions that do not
      alter the facial architecture as regard of facial typology, skeletal class and
      pattern of development to a severe disturbance of those. There is a degree of
      clinical heterogeneity between subjects with Prader-Willi syndrome on clinical
      evaluation and cephalometric study confirms the heterogeneity for this patients.
      Because the identification of smaller dimensions for majority of parameters in
      children and adults, the possibility of developmental delay or growth retardation
      delay can be excluded. These findings are important for the orthodontist for
      optimum timing of orthodontic management of patients with Prader-Willi syndrome.

PMID- 22990544
TI  - Breast invasive lobular carcinoma: a retrospective clinicopathologic study of 25
      cases.
AB  - Invasive lobular carcinoma (ILC) is the second most common type of invasive
      breast cancer, having distinct prognostic and biologic implications. As an
      objective of the present work, we analyzed the clinicopathologic characteristics
      and prognostic factor of this invasive breast cancer variant. Clinical and
      morphological data of 25 cases of ILC collected during 2006-2011 were reviewed.
      Histopathologically, 11 cases were of classic type, and the others were non
      classic with solid and histiocytoid subtypes being mostly encountered. Overall
      the non-classic ILC type was diagnosed in more aged patients (with a median age
      at onset of 59 years), with a predominance for a more advanced tumor degree
      differentiation (78.5% as grade 2 and 3), in advanced pTNM stages (50% in stage
      III and IV), with 50% lymph node involvement and with over 70% ER and Her2
      reactivity. Statistically, we found that for the solid variant prevailed a PR+
      and Her2- status while in histiocytoid subtype the PR- and Her2+ immunoprofile
      was most encountered. We conclude that non-classic ILC type represents a distinct
      entity of invasive breast carcinoma with a worsen prognostic than the
      conventional ILC type.

PMID- 22990545
TI  - The prognostic value of the immunohistochemical aspects of tumor suppressor genes
      p53, bcl-2, PTEN and nuclear proliferative antigen Ki-67 in resected colorectal
      carcinoma.
AB  - This study aim was to identify the relations between tumor suppressor genes (p53,
      bcl-2, PTEN), nuclear proliferative antigen Ki-67 and epidemiologic, morphologic
      and histologic patient related factors, in colorectal cancer. MATERIALS AND
      METHODS: Twenty-two prospectively collected colorectal cancer resection specimens
      were histologically prepared, using standard paraffin-embedded and Hematoxylin
      Eosin staining method; for immunohistochemical study, the Streptavidin-Biotin
      (sABC)/Horseradish Peroxidase (HRP) method was used. RESULTS: P53 was positive in
      86.36% of cases, more intense (>50%) in rectal cancer and in women 59.16 +/- 9.49
      year-old; the G1/2 adenocarcinoma was dominant. Bcl-2 was positive in 18.18% of
      the cases, in distal colorectal cancer, only in men, 63.5 +/- 13.2-year-old. PTEN
      was positive in 95.45% of the cases; intense positivity was recorded in 12 men
      and six women, 61.47 +/- 11.67-year-old, in rectal topography. Ki-67 was positive
      in 86.36% of the cases, more intense in four men and four women, 63.45 +/- 12.22
      year-old, in proximal and advanced colorectal cancers (pT3N1/2 - 62.5%).
      CONCLUSIONS: Tumor suppressor genes mutations are often present in colorectal
      cancer; the intensity of the expression of these mutations varies, which could
      explain the different prognosis for these patients.

PMID- 22990546
TI  - Macroscopic and microscopic findings in avascular necrosis of the femoral head.
AB  - The avascular necrosis of the femoral head is an illness induced by the cutoff of
      blood flow to the femoral head and it affects mostly young adults between the
      ages of 30 and 50 years, raising therapeutic and diagnostic issues. Many risk
      factors are incriminated in the development of avascular necrosis of the femoral
      head like: trauma, chronic alcohol consumption, smoking, administration of
      corticosteroid drugs, most of the cases are considered to be idiopathic. The main
      goal of our paper is to describe the macroscopic and microscopic variations of
      the bone structure, which occur in patients with avascular necrosis of the
      femoral head. MATERIALS AND METHODS: The biological material needed for our study
      was obtained following hip arthroplasty surgery in 26 patients between the ages
      of 29 and 59 years, which previously were diagnosed with avascular necrosis of
      the femoral head and admitted in the Orthopedics Department of the Emergency
      County Hospital of Craiova (Romania) between 2010 and 2011. From a macroscopic
      point of view, we found well defined areas of necrosis, most of which were neatly
      demarcated of the adjacent viable tissue by hyperemic areas, loss of shape and
      contour of the femoral head and transformations of the articular cartilage above
      the area of necrosis. When examined under the microscope, we found vast areas of
      fibrosis, narrow bone trabeculae, obstructed blood vessels or blood vessels with
      clots inside, hypertrophic fat cells, bone sequestration but also small cells and
      pyknotic nuclei. The microscopic and macroscopic findings on the femoral head
      sections varied with the patients and the stage of the disease.

PMID- 22990547
TI  - EGFR, HER2/neu and Ki67 immunoexpression in serous ovarian tumors.
AB  - In this study, we analyzed EGFR, HER2/neu and Ki67 immunoexpression for 26
      benign, borderline and malignant serous ovarian tumors. EGFR and HER2/neu
      immunoreactions were present in some benign/borderline tumors with high/low
      intensity of immunostain. In poorly differentiated adenocarcinomas, the
      EGFR/HER2/neu reaction was intense compared to well-differentiated ones. The Ki67
      medium proliferation index was 2.1% for benign tumors, 6% in the borderline and
      47.7% in malignant tumors. EGFR, HER2/neu and Ki67 can be used to identify
      benign/borderline tumors with progression potential and the malignant aggressive
      tumors.

PMID- 22990548
TI  - Histomorphometric study regarding the evolution under treatment of the changes
      appearing at the level of the gingival mucosa in diabetic children.
AB  - The values of the glucose influence the status of the periodontium, but also the
      periodontitis influences the glucose balance by increasing the resistance to
      insulin. In the case of children in the first step the gingivitis appears, than
      if the glucose control is not made and the dental hygiene is defective the
      evolution is towards advanced periodontal disease. The present histomorphometric
      study wants to emphasize the eventual changes that appear at the level of the
      gingival epithelium before and after starting a correct treatment of the
      periodontal disease. The histomorphometric study indicates an average nuclear
      area of the keratinocytes of 211.65 MUm2 in the batch studied before the
      application of the treatment and an increase of the average nuclear area to
      234.88 MUm2 after the treatment (p=0.010538). The nuclear volume before the
      treatment has an average value of 2396.61 MUm3, after the treatment it reaches
      the value of 2996.924 MUm3. The area of the keratinocytes has an average of
      495.43 MUm2, after the treatment it reaches the value of 724.89 MUm2, noticing a
      14.6% (p=0.004) increase of the cellular area. Before the treatment, we notice a
      ballooning of the cells from the intermediary level, the existence of some
      pyknotic nuclei and the disappearance of the nucleoli. The associated gingival
      pathology diabetes mellitus type 1 in the case of children and teenagers is
      treatable within six months, macroscopically and microscopically the gingival
      mucosa approaching to normal conditions. In the case of children and teenagers
      diagnosed with type 1 diabetes, the dental check is mandatory in order to prevent
      the gingival and periodontal diseases.

PMID- 22990549
TI  - Nervous structure of Meckel's diverticulum in children.
AB  - Meckel's diverticulum, being considered as the most frequent malformation of the
      digestive tract, has been largely presented in scientific papers, but a complete
      physiopathological mechanism for its natural history has not been yet described.
      We have studied the nervous system and the differences observed in eight Meckel's
      diverticulums with enteric or ectopic gastric mucosa, using specific
      immunohistochemical markers. It has been noted a significantly higher density of
      myenteric nerve fibers in areas with enteric mucosa compared with the areas with
      gastric heterotopias, while the transition zone had intermediate nerve fibers
      density. The ileal wall near the diverticulum had a myenteric plexus density
      similar to gastric mucosa intradiverticular area. The density of Meckel's
      diverticulum myenteric plexuses determines the local peristalsis. The enteric
      type mucosa diverticulums has more intense peristaltic activity which leads more
      frequent to intussusception or, in case of intraluminal obstruction, might be
      also involved in germ spreading and progression of infectious process. The lower
      density of Auerbach's plexus nerve fibers in cases with gastric heterotopia
      Meckel's diverticulum determines less effective drainage of diverticular content,
      favoring the contact of intradiverticular mucosa with acid secretion of gastric
      mucosa area. The gastric mucosa's defense mechanisms and the intense peristaltic
      activity in the zone with enteric mucosa offer a certain protection against the
      apparition of intradiverticular ulcerative lesions, which usually are observed on
      the ileum, near the diverticulum. The age related decreasing number of myenteric
      nerve fibers density explains the higher frequency of Meckel's diverticulum
      complications in children.

PMID- 22990551
TI  - VEGF and CD105 immunoexpression in squamous cervical carcinomas and associated
      precancerous lesions.
AB  - In this study, we analyzed the VEGF and CD105 immunoexpression in 24 cervical
      squamous cell carcinomas and CIN associated lesions with different degrees. For
      both lesions, MVD values were higher in patients who had associated risk factors.
      VEGF and MVD expression increased in both categories for high-grade lesions,
      respectively CIN III lesions compared with CIN I/II and poorly differentiated
      carcinomas compared with well-differentiated ones. Also, there was a
      statistically significant association between VEGF and MVD in poorly
      differentiated carcinoma and CIN III. The study indicated that analyzed markers
      were specific for both early and advanced stages of cervical angiogenesis.
      Maximum values of VEGF and MVD in CIN III designate this lesion as critical to
      the progression of neoplasia.

PMID- 22990550
TI  - Psychological impact of burn scars on quality of life in patients with extensive
      burns who received allotransplant.
AB  - With the remarkable progress in the field of burns treatment, the outcome of
      extensive burns improved significantly. The increased likelihood of survival of a
      burn victim heightens concerns for potential psychological morbidity for the
      survivors. Hypertrophic scarring is devastating and can result in disfigurement
      that affects quality of life. To assess the impact of burn scars on the quality
      of life of the survivors, we used two scales: the WHOQOL-BREF questionnaire to
      evaluate the quality of life and the POSAS scale for the subjective evaluation of
      the post-burn scars in 26 patients who suffered extensive burns and received
      allotransplant. A significant correlation was observed between the WHOQOL-BREF
      score and POSAS scale (r=-0.93, p<0.001). In conclusion, burn scar visibility and
      severity did have a strong relationship with the quality of life in the survivors
      of a major burn who received allotransplant. Therefore, more effort must be
      placed into developing psychosocial interventions that help survivors to accept
      scars, reduce depression and build a strong supportive system.

PMID- 22990552
TI  - Macroscopic, mesoscopic and microscopic morphology of the gastric plexus-
      ontogeny of the celiac ganglion.
AB  - The vagus trunks, anterior and posterior, and their respective branches control
      the parasympathetic innervation of the stomach. After giving off a few thin
      branches, at the lower part of the esophagus and the cardiac region of the
      stomach, the anterior vagal trunk divides into its main branches: four or five
      consecutive direct branches which supply the upper part of the lesser curvature;
      these nerves do not form  plexuses and thus, they may be individually dissected.
      One of the branches is stronger than the others and is called the principal
      anterior nerve of the lesser curvature (anterior nerve of Latarjet). The present
      study was conducted on eight fetuses of different gestational age (resulting from
      spontaneous abortions, without malformations), observing the Romanian laws of
      professional ethics, and 15 adult cadavers (male and female) whose celiac region
      was dissected macro- and mesoscopically to reveal both the celiac ganglia and
      their afferent and efferent vessels. For the microscopic study, we used the
      Bielschowsky silver staining method. The meso- and macroscopic dissections
      revealed the anterior and posterior vagal trunks in all the specimens (100%), as
      well as a rich gastric periarterial plexus. The microscopic samples focused on
      the ontogeny of the celiac ganglion in various gestational stages.

PMID- 22990553
TI  - The immunoexpression of EGFR and Her2/neu in oral squamous carcinoma.
AB  - In this study, we have analyzed the EGFR and Her2/neu expression in oral squamous
      carcinoma and adjacent dysplastic areas. The lesions were diagnosed especially in
      the sixth decade of life, in male patients, localized on the lips, especially as
      well and poorly differentiated carcinomas (34%). The EGFR immunostain has been
      intense in over 50% of the tumors cells in well-differentiated carcinomas,
      expression diminished in the moderately and poorly differentiated carcinomas.
      Her2/neu marker recorded a score of 3+ in moderately and poorly differentiated
      carcinomas, the reaction turning out positive in 25% of the cases.

PMID- 22990554
TI  - Immunohistochemical expression of CK7, CK5/6, CK19, and p63 in Warthin tumor.
AB  - Our study included a number of 24 cases with Warthin tumor, diagnosed between
      2007-2011, which were analyzed in terms of clinical, histopathological and
      immunohistochemistry point of view, using CK7, CK5/6, CK19, and p63 antibodies.
      Warthin tumor is most often a tumor with a slow evolution, painless, usually
      affecting males (M/F 3.2/1) in the seventh decade of life. Histopathologically,
      it is distinguished the predominance of the typical forms of the tumor, with a
      balanced ratio epithelium/stroma. The immunostaining for CK7 showed positivity in
      all the investigated cases both in the columnar luminal cells and basal cells.
      The immunostaining for CK5/6 was positive in all the investigated cases in
      bilayer epithelial basal cells, both in the structure of the cysts and the
      papillae. In the case of the immunostaining for p63 we noticed limited nuclear
      positivity in the basal cells, while the columnar cells' nucleus were negative.
      The immunohistochemical study of the bilayer epithelial component of Warthin
      tumor showed different immunstaining of the two types of epithelia, the
      oncocytary columnar and the basal on, similar to those found in the salivary
      gland ducts.

PMID- 22990555
TI  - Association between liver histology, carotid ultrasonography and retinal vascular
      changes in patients with nonalcoholic fatty liver disease (NAFLD).
AB  - INTRODUCTION: The prevalence of nonalcoholic fatty liver disease (NAFLD) is
      increasing all over the world. NAFLD has been demonstrated to be associated with
      carotid artery atherosclerosis, evaluated using the intima-media thickness (IMT).
      In this article, we focused on the association between NAFLD, carotid parameters
      such as: intima-media thickness (IMT), pulsatility index (PI) and resistivity
      index (RI) as markers of subclinical atherosclerosis and the presence of retinal
      vascular disorders. PATIENTS AND METHODS: We compared carotid IMT, pulsatility
      and resistivity index evaluated by ultrasonography, in 10 patients with
      histological-proven NAFLD and retinal vascular changes (retinophotographies).
      RESULTS: The degree of hepatic steatosis, necroinflammation and fibrosis in NAFLD
      patients was strongly associated with the value of carotid IMT and also with PI
      and RI. Moreover, there seems to be a connection between the degree of NAFDL and
      the retinal vascular changes in patients with carotid atherosclerosis.
      CONCLUSIONS: These results suggest that the severity of liver histopathological
      lesions among NAFLD patients is strongly associated with carotid parameters: IMT,
      IP, IR and also with retinal vascular changes. Further controlled studies are
      needed to confirm the results.

PMID- 22990556
TI  - Cervical adenocarcinoma: a retrospective clinicopathologic study of 16 cases.
AB  - Endocervical adenocarcinomas account for about 10-30% of cancers of the uterine
      cervix and display a variety of disparate morphologies. As an objective of the
      present work, we analyzed the clinicopathologic characteristics and prognostic
      factor of cervical adenocarcinoma. Clinicomorphological data of 16 cases of
      endocervical adenocarcinoma were reviewed during 2006-2011. Histopathologically,
      seven cases were of mucinous endocervical type, one intestinal type, two mucinous
      villoglandular type, four endometrioid type and two of serous type. The
      immunohistochemical investigation showed a tipically endocervical carcinoma
      profile ER-/PR-/Vim-/CEA+ in 10 cases (62.5%), which morphologically corresponded
      to: five mucinous endocervical type, one villoglandular type, three endometrioid
      type and one serous type. Regarding the prognosis we established that
      endometrioid endocervical adenocarcinoma is the histological variant with the
      worst prognosis, most cases been diagnosed in advanced stages (IIIA and IIIB)
      while at the opposite pole were papillary villoglandular and serous endocervical
      adenocarcinomas, diagnosed in less advanced stages of disease (IB and IIB). We
      concluded that the clinicomorphological diagnosis of endocervical adenocarcinoma
      is a challenging task, given to its multitude of histological variants and to the
      fact that immunohistochemistry investigations proved to be useful in only 63% of
      cases. In addition, we confirmed that the clinical stage is the most important
      prognostic factor and to some extent, the histomorphologic features can condition
      the biological behavior of these tumors.

PMID- 22990557
TI  - High-grade poorly differentiated retroperitoneal sarcoma. Report of a case and
      review of the literature.
AB  - Retroperitoneal sarcomas (RPS) are uncommon tumors associated with a poor
      prognosis. This is particularly true in case of high-grade sarcomas of specific
      histological subtypes, as demonstrated by the largest surveys of the last decade.
      Up to the present day, unfortunately there are no powerful tools available except
      for surgery. On the other hand, the resection rate of RPS is significantly
      increased over the last decades allowing to deliver the best treatment available.
      This paper reports on the case of a young patient who was incidentally diagnosed
      with a retroperitoneal mass. The patient underwent surgery in our department and
      the histological report showed a spindle cell sarcoma of high grade of malignancy
      with an incomplete muscular phenotype. The patient was discharged on the seventh
      postoperative day and he is still free of local and distant recurrence.

PMID- 22990558
TI  - The association of polymorphonuclears with humps in acute postinfectious
      glomerulonephritis.
AB  - It is currently considered that hump dense deposits developed during an acute
      poststreptococcal glomerulonephritis become finally dissolute by three
      hypothetical mechanisms: loosing their electron density, internalization and
      processing by podocytes and by incorporation in the glomerular basal lamina
      (GBM). Analyzing ultrastructurally the association of polymorphonuclear
      leukocytes and hump deposits, we emphasized features endorsing the hypothesis
      that the immune complexes of dense deposits are discharged in the circulation
      under the leukocytes activity. The active polymorphonuclear cells are melting the
      GBM in the area of contact by complement activation and by the NAPlr bound
      plasmin. The reversed flow of immune complexes from humps towards the blood
      circulation leaves fading, wrinkled shaped humps, before total dissolution.

PMID- 22990559
TI  - Abnormal bilateral drainage of testicular veins: embryological aspects and
      surgical application.
AB  - A combination of unusual bilateral drainage of the testicular veins observed in a
      male cadaver utilized for educational and research purposes is prescribed. In
      specific, the right testicular vein was terminated on the right renal vein at
      almost right angle, whereas the left testicular vein was bifurcated into a
      lateral component drained into the left renal vein and a medial component opened
      into the inferior vena cava close to its confluence with the left renal vein.
      Such a co-existence of bilateral testicular vein termination is very rarely
      presented in the literature. The main goal of this study is to provide an
      embryological development model for these variants and to highlight the likely
      occurrence of these anomalies to the surgeon of the region. The awareness of
      these venous anomalies can facilitate the surgeons in order to ligate properly
      and adequately the abnormal venous terminations and collaterals reducing that way
      the recurrence rate of varicocele.

PMID- 22990560
TI  - Clinical, morphological and immunohistochemical characterization of a recurrent
      B1 type thymoma.
AB  - Type B1 thymoma is widely accepted as a tumor with a non-aggressive behavior even
      in advanced stage. Most of these tumors are classified as Masaoka stage I or II.
      They rarely relapse or metastasize and the surgical treatment is considered
      curative. We have investigated a case of thymoma type B1, which relapsed 13
      months after the primary tumor was excised. The patient was diagnosed with a
      local tumor recurrence after investigations due to the worsening of clinical
      symptoms of myasthenia gravis (MG). The therapy management of such cases is
      debatable and protocols not yet approved. For this reason, we have analyzed
      different clinical, morphological and immunohistochemical characteristics that
      may be considered as prognostic factors for a more aggressive behavior of such
      tumors. We have identified some morphologic characteristics rarely seen in this
      type of thymoma but none considered of prognostic value. In addition, we
      investigated some possible immunohistochemical markers that are generally
      associated with a more aggressive clinical outcome in different malignant tumors
      and thymic epithelial tumors. Among these markers, only p53 was positive and may
      be useful to predict a more aggressive evolution. In summary, probably the more
      appropriate approach of the patient is the clinical follow-up together with
      treatment of the clinical symptoms of myasthenia gravis.

PMID- 22990561
TI  - Refractory anemia with ring sideroblasts associated with marked thrombocytosis:
      case report and literature review.
AB  - "Refractory anemia with ring sideroblasts and thrombocytosis" (RARS-T) is a rare
      disease, a provisional entity, with a controversial status in the 2008 revised
      WHO classification. Even at present time, RARS-T is a matter of debate whether it
      is a distinct clinicopathological entity or more likely a constellation of
      clinical and pathological features of two well-defined myeloid neoplasms,
      myelodysplastic syndrome and myeloproliferative neoplasm. Perhaps none of the
      clonal disorders illustrates better the challenges presented by the current
      classification of myeloid neoplasms, than this clinical entity with overlapping
      features of both refractory anemia with ring sideroblasts and essential
      thrombocythemia. The purpose of this study is to present the evolution of such a
      case, with difficulties in establishing not only the correct diagnosis, but also
      the appropriate therapeutic approach. For this reported case, we present
      documented details regarding persistent thrombocytosis, slightly increased number
      of leukocytes and analysis of Janus kinase 2 (JAK2) genes that revealed a V617F
      mutation, confirming the presence of an underlying myeloproliferative neoplasm,
      followed later in the evolution by occurrence of myelodysplastic features as ring
      sideroblasts. This case might interest pathologists, but especially clinicians,
      for at least two reasons: the rarity of this disease and the lack of data on
      prognosis of these patients, probably because of relatively recent established
      diagnosis criteria and existence of few studies with small number of patients.
      The third interesting aspect for practitioners would be the absence of consensus
      on optimal clinical treatment for this disorder, because there are few cases that
      meet the rigorous diagnostic criteria.

PMID- 22990562
TI  - Vestibulary rehabilitation--election treatment method for compensating vestibular
      impairment.
AB  - OBJECTIVE: This paper aims to reveal the actual benefit of vestibular
      rehabilitation (VR) in patients with unilateral vestibular loss. PATIENT AND
      METHODS: Case report of a young female patient with acute unilateral vestibular
      loss due to facial nerve schwannoma developed above the internal auditory canal
      (IAC) from where it seems to have entered the IAC. Betahistine associated to VR
      treatment was recommended due to persisting imbalance after tumor removal. The
      benefit of the combined therapy was evaluated objectively (sensory organization
      test) and subjectively (questionnaires regarding self-perception of the deficit
      in quality of life). RESULTS: Both evaluations revealed great improvement in
      stability (SOT scores) as well as in health-related quality of life (HRQoL)-
      improvement of self-perception scores of disequilibrium in all questionnaires
      used. CONCLUSIONS: Combined recommended treatment (betahistine and VR) improves
      HRQoL after acute unilateral vestibular loss. It reduces self-perceived
      disability and intensity of symptoms during usual activities.

PMID- 22990563
TI  - Congenital bilateral agenesis of the tibialis anterior muscles: a rare case
      report.
AB  - Congenital bilateral agenesis of the tibialis anterior muscles is a rare
      condition. We present a case of congenital absence of bilateral tibialis anterior
      muscles in a 6-year-old boy who presented with an abnormal gait. He was
      previously diagnosed to have bilateral congenital talipes equinovarus (CTEV)
      deformity for which he underwent corrective surgery two times. However, he still
      had a residual foot problem and claimed to have difficulty in walking. On
      examination, he walked with a high stepping gait and muscle power of both lower
      limbs was 5/5 on the medical research council scale (MRCS) except for both ankle
      dorsiflexors and long toe extensors. The sensation was intact. Magnetic Resonance
      Imaging (MRI) study of both legs revealed that tibialis anterior muscles were not
      visualized on both sides suggestive of agenesis of the tibialis anterior muscles.
      The rest of the muscles appeared mildly atrophied. The electrophysiological study
      showed normal motor and sensory conduction in both upper and lower limbs.
      Electromyographic (EMG) study of the vastus medialis was within normal limit and
      no response could be elicited for EMG of tibialis anterior muscles suggesting
      possible absence of tibialis anterior muscles, bilaterally. The patient underwent
      split tibialis posterior tendon transfer to achieve a balanced and functional
      foot and was well on discharge. The present case describes the normal anatomy and
      embryology of tibialis anterior muscles as well as possible causes of its
      agenesis along with its clinical implications.

PMID- 22990565
TI  - Can GPS be used to detect deleterious progression in training volume among
      runners?
AB  - There is a need to ascertain if an association exists between excessive
      progression in weekly volume and development of running-related injuries (RRI).
      The purpose of this study was to investigate if GPS can be used to detect
      deleterious progression in weekly training volume among 60 novice runners
      included in a 10-week prospective study. All participants used GPS to quantify
      training volume while running. In case of injury, participants attended a
      clinical examination. The 13 runners who sustained injuries during follow-up had
      a significantly higher weekly progression in total training volume in the week
      before the injury origin (86% [95% confidence interval: 12.9-159.9], p = 0.026)
      compared with other weeks. Although not significant, participants with injuries
      had an increase in weekly training volume of 31.6% compared with a 22.1% increase
      among the healthy participants. The error of the GPS measurements in open
      landscape, forest, and urban area of volume was <=6.2%. To conclude, no
      clinically relevant measurement errors of the GPS devices were found for training
      volume. Based on this, GPS has a potential to detect errors in training volume,
      which may be associated with development of RRI. Based on the results from the
      current study, increases in weekly training progression may become deleterious at
      a weekly increase above 30%, which is more than the 10% rule currently used as a
      guideline for correct progression in weekly volume by runners and coaches. Still,
      no clear evidence for safe progression of weekly volume exists. But it seems
      likely that some individuals may tolerate weekly progressions around 20-25%, at
      least for a short period of time.

PMID- 22990564
TI  - Evaluation of novel tests of neuromuscular function based on brief muscle
      actions.
AB  - Although widely used, the standard strength test (SST) is known to provide
      moderate correlations with functional measures, while being based on sustained
      maximum forces and a relatively large number of trials. The aim of this study was
      to compare the concurrent (with respect to SST) and external validity (with
      respect to the standard balance and maximum power output tests) of 2 alternate
      tests of neuromuscular function based on brief isometric actions. The first test
      provides a slope between the rates of torque development (RTD) and peak torques
      (T) measured from a number of consecutive rapid actions performed across a wide
      range of T levels (brief force pulses, BFP). The second test (alternating
      consecutive maximum contractions, ACMC) provides T and RTD from multiple cycles
      of rapid alternating maximum actions of 2 antagonistic muscle groups. The results
      obtained from 29 young and healthy subjects revealed moderate-to-high concurrent
      validity of ACMC (median r = 0.56, p < 0.05) and its similar, if not higher
      external validity than SST. Conversely, both the concurrent and external validity
      of BFP seemed to be relatively low (r = 0.23, p > 0.05). Because ACMC could also
      have advantage over SST by being based on somewhat lower and transitional muscle
      forces exerted and fewer trials are needed for testing 2 antagonistic muscles,
      the authors conclude that ACMC could be considered as either an alternative or
      complementary test to SST for testing the ability for rapid exertion of maximum
      forces. Conversely, BFP may offer a measure of the neuromuscular system "as a
      whole" that is complementary to SST by providing outcomes that are relatively
      independent of muscle size and function.

PMID- 22990566
TI  - The accuracy of the body adiposity index for predicting body fat percentage in
      collegiate female athletes.
AB  - The body adiposity index (BAI) is a new simplistic method for predicting body fat
      percentage (BF%) via a simple equation of hip circumference to height. A
      scientific study of this novel method in athletic groups is warranted because of
      the possibility of it serving as an inexpensive field technique. The purpose of
      this study was to cross-validate the BAI for predicting BF% in a group of
      collegiate female athletes by using dual-energy x-ray absorptiometry (DXA) as the
      criterion variable. Thirty college-aged female athletes (age = 20.0 +/- 1.3
      years) participated in this study. For each participant, BF% was obtained with
      the BAI method and compared with DXA. The mean BF% was 27.1 +/- 3.4 by the BAI
      and 26.7 +/- 5.9 from DXA, which was not significantly different (p > 0.05).
      However, the BAI did not provide a significant correlation with the DXA (r =
      0.28, R2 = 0.08, p > 0.05) and resulted in a standard error of estimate = 5.78%
      and total error = 5.84%. Bland-Altman plot showed that the limits of agreement
      (95% confidence intervals) between the DXA and BAI ranged between -10.2 and
      11.8%, and there was a significant negative association between the difference
      and mean of the 2 methods (r = -0.52, p < 0.01). The results of this
      investigation indicate that BAI results in large individual errors when
      predicting BF% in female athletes and has a tendency to provide overestimated
      values as BF% decreases. Therefore, this method should not be used for predicting
      individual BF% in athletic women.

PMID- 22990567
TI  - Training practices and ergogenic aids used by male bodybuilders.
AB  - Bodybuilding involves performing a series of poses on stage where the competitor
      is judged on aesthetic muscular appearance. The purpose of this study was to
      describe training practices and ergogenic aids used by competitive bodybuilders
      and to determine whether training practices comply with current recommendations
      for muscular hypertrophy. A web-based survey was completed by 127 competitive
      male bodybuilders. The results showed that during the off-season phase of
      training (OFF), the majority of respondents performed 3-6 sets per exercise
      (95.3%), 7-12 repetition maximum (RM) per set (77.0%), and 61- to 120-seconds
      recovery between sets and exercises (68.6%). However, training practices changed
      6 weeks before competition (PRE), where there was an increased number of
      respondents who reported undertaking 3-4 sets per exercise at the expense of 5-6
      sets per exercise (p < 0.001), an increase in the number reporting 10-15RM per
      set from 7-9RM per set (p < 0.001), and an increase in the number reporting 30-60
      seconds vs. 61-180 seconds recovery between sets and exercises (p < 0.001).
      Anabolic steroid use was high among respondents competing in amateur competitions
      (56 of 73 respondents), whereas dietary supplementation was used by all
      respondents. The findings of this study demonstrate that competitive bodybuilders
      comply with current resistance exercise recommendations for muscular hypertrophy;
      however, these changed before competition during which there is a reduction
      resistance training volume and intensity. This alteration, in addition to an
      increase in aerobic exercise volume, is purportedly used to increase muscle
      definition. However, these practices may increase the risk of muscle mass loss in
      natural compared with amateur bodybuilders who reportedly use drugs known to
      preserve muscle mass.

PMID- 22990568
TI  - Running demands and heart rate response in rugby sevens referees.
AB  - The purpose of this study was to examine for the first time the match running
      demands and heart rate (HR) responses associated with elite rugby sevens
      referees. Twelve referees were analyzed over 38 games, using Global Positioning
      System. Referees covered an average distance of 1665.2 +/- 203.5 m per game (15.1
      +/- 0.5 minutes). Over this distance, 22.3% (371.8 +/- 48.9 m) was spent standing
      and walking, 25.9% (431.2 +/- 92.6 m) jogging, 12.4% (206.5 +/- 53.2 m) cruising,
      23.8% (395.6 +/- 94.3 m) striding, 8% (133.3 +/- 61.6 m) high-intensity running,
      and 7.6% (126.7 +/- 87.3 m) sprinting. The average maximal distance of sprints,
      the number of sprints, and the mean sprint distance over the game were 31.3 +/-
      13.4 m, 5.76 +/- 3.6 sprints, and 19.9 +/- 7.8 m, respectively. The referee's
      work-to-rest ratio was 3.5:1. There were no statistical differences between the
      first and second half in any of the running variables analyzed. The average HR in
      the second half (160 +/- 9 b.min(-1); 86 +/- 5% maximal heart rate (HRmax) of the
      estimated) was higher (p < 0.05) than the HR recorded in the first half (154 +/-
      11 b.min(-1); 83 +/- 6% of the estimated HRmax). This study also suggests that
      the physical demands of referring in rugby sevens are quite different from those
      encountered in other rugby codes, and the training regimes need to meet the
      increased overall running demands and high-intensity running activity.

PMID- 22990569
TI  - Familiarization and reliability of one repetition maximum strength testing in
      older women.
AB  - Strength is a fundamental component of physical fitness, and therefore should be
      precisely assessed. The purpose of this study was to analyze the number of
      testing sessions required to achieve consistent 1 repetition maximum (1RM)
      strength measurements in untrained older women. Forty-five untrained older women
      were measured for 1RM in bench press machine (BP), leg extension (LE) machine,
      and free weight arm curl (AC). Reliability coefficients for trials 1 and 2 for BP
      (intraclass correlation coefficient [ICC] = 0.973) and LE (ICC = 0.976) were
      higher than for AC (ICC = 0.953). Percent change from trial 1 to 2 for BP (3.5 +/
      10.9%) and AC (3.8 +/- 8.1%) was less than for LE (5.4 +/- 6.2%), but all were
      significant increases between trials (p < 0.05). Trial differences were reduced
      to nonsignificant levels (p > 0.05) in the third trial for BP (0.0 +/- 0.0%), LE
      (1.2 +/- 3.0%) and AC (2.7 +/- 5.9%). Reliability coefficients rose for BP and LE
      (ICC = 0.999) and AC (ICC = 0.963) when a third trial was performed. Bland and
      Altman plotting showed very small bias and limits of agreement (LoA) for both the
      exercises (BP: bias = 0 kg, limits of agreement = 0 kg; LE: bias = -0.16 kg, LoA
      = 2.21 kg; AC: bias = -0.11 kg, LoA = 1.72 kg). This approach to determine 1RM
      strength values produced rapid lifting technique familiarization resulting in a
      need of 2 to 3 test sessions to achieve consistent 1RM measurements in untrained
      older women.

PMID- 22990570
TI  - Kinematics of the trunk and the lower extremities during restricted and
      unrestricted squats.
AB  - Squatting is a common strength training exercise used for rehabilitation, fitness
      training, and in preparation for competition. Knowledge about the loading and the
      motion of the back during the squat exercise is crucial to avoid overuse or
      injury. The aim of this study was the measurement and comparison of the
      kinematics of the lower leg, trunk, and spine during unrestricted and restricted
      (knees are not allowed beyond toes) squats. A total of 30 subjects performed
      unrestricted and restricted barbell squats with an extra load of 0, 25, and 50%
      bodyweight. Motion was tracked using a 12-camera Vicon system. A newly developed
      marker set with 24 trunk and 7 pelvic markers allowed us to measure 3D segmental
      kinematics between the pelvic and the lumbar regions, between the lumbar and the
      thoracic segments, and the sagittal curvatures of the lumbar and the thoracic
      spine. In an unrestricted squat, the angle of the knee is larger and the range of
      motion (ROM) between the lumbar and the thoracic segments is significantly
      smaller compared with a restricted squat (p < 0.05). The studied subjects showed
      significantly increased ROM for thoracic curvature during restricted squats. The
      unrestricted execution of a squat leads to a larger ROM in the knee and smaller
      changes in the curvature of the thoracic spine and the range of smaller segmental
      motions within the trunk. This execution in turn leads to lower stresses in the
      back. To strengthen the muscles of the leg, the unrestricted squat may be the
      best option for most people. Thus, practitioners should not be overly strict in
      coaching against anterior knee displacement during performance of the squat.

PMID- 22990571
TI  - A job analysis of major college female strength and conditioning coaches.
AB  - This investigation consisted of a job analysis of 6 National Collegiate Athletic
      Association (NCAA) Division I female strength and conditioning coaches. Each
      coach was employed at universities competing within the Football Bowl
      Subdivision. All subjects in the survey were responsible for providing strength
      and conditioning services to their institution's athletic programs. The
      procedures used for the gathering of data involved a questionnaire followed by a
      semi-structured interview. The purpose of this format was to use the semi
      structured interview to delve more deeply into the issues raised by the
      questionnaire. Evidence was obtained related to demographic data; major job
      duties; relationships with supervisors, fellow strength coaches, and the sport
      coaches with whom they work; and the effects the job has on their spouse and
      other family members. All the participants in the study were white with an
      average age of 31.6 years. Their average time spent in the profession was 8
      years, and the average time spent in their current employment was 5 years.
      Overall, the job satisfaction for the group was high. Five of the subjects held
      master's degrees, and all participants held relevant certifications in the field.
      The coaches primarily provided services to athletes participating in women's
      sports at their respective universities.

PMID- 22990572
TI  - Physiologic performance test differences in female volleyball athletes by
      competition level and player position.
AB  - The purpose of this study was to examine physiologic performance test differences
      by competition level (high school and Division-I collegiate athletes) and player
      position (hitter, setter, defensive specialist) in 4 volleyball-related tests. A
      secondary purpose was to establish whether a 150-yd shuttle could be used as a
      field test to assess anaerobic capacity. Female participants from 4 varsity high
      school volleyball teams (n = 27) and 2 Division-I collegiate volleyball teams (n
      = 26) were recruited for the study. Participants completed 4 performance-based
      field tests (vertical jump, agility T-test, and 150- and 300-yd shuttle runs)
      after completing a standardized dynamic warm-up. A 2-way multivariate analysis of
      variance with Bonferroni post hoc adjustments (when appropriate) and effect sizes
      were used for the analyses. The most important findings of this study were that
      (a) college volleyball athletes were older, heavier, and taller than high school
      athletes; (b) high school athletes had performance deficiencies in vertical
      jump/lower-body power, agility, and anaerobic fitness; (c) lower-body power was
      the only statistically significant difference in the performance test measures by
      player position; and (d) the correlation between the 150- and 300-yd shuttle was
      moderate (r = 0.488). Female high school volleyball players may enhance their
      ability to play collegiate volleyball by improving their vertical jump, lower
      body power, agility, and anaerobic fitness. Furthermore, all player positions
      should emphasize lower-body power conditioning. These physical test scores
      provide baseline performance scores that should help strength and conditioning
      coaches create programs that will address deficits in female volleyball player
      performance, especially as they transition from high school to college.

PMID- 22990573
TI  - Skeletal muscle myosin heavy chain isoform content in relation to gonadal
      hormones and anabolic-catabolic balance in trained and untrained men.
AB  - Gonadal hormones and anabolic-catabolic hormone balance have potent influence on
      skeletal muscle tissue, but little is known about their action with regard to
      myosin heavy chain (MHC) transformation in humans. We investigated the
      relationship between skeletal muscle MHC isoform content in the vastus lateralis
      muscle and basal testosterone (T) concentration in 3 groups of subjects:
      endurance trained (E), sprint/strength trained (S), and untrained (U) young men.
      We have also determined basal sex hormone-binding globulin and cortisol (C)
      concentrations in untrained subjects to examine the relationship between MHC
      composition and the anabolic-catabolic hormone balance. Moreover, basal free
      testosterone (fT) and bioavailable testosterone (bio-T) concentrations were
      calculated for this subgroup. Despite significant differences in MHC isoform
      content (69.4 +/- 2.39%, 61.4 +/- 8.04%, and 37.5 +/- 13.80% of MHC-2 for groups
      S, U, and E, respectively, Kruskal-Wallis: H = 18.58, p < 0.001), the T
      concentration was similar in the three groups of subjects (18.84 +/- 5.73 nmol.L(
      1), 18.60 +/- 5.73 nmol.L(-1), and 20.73 +/- 4.06 nmol.L(-1) for U, E, and S
      groups, respectively, Kruskal-Wallis: H = 1.11, p > 0.5). We have also found that
      in the U group, type 2 MHC in the vastus lateralis muscle is positively
      correlated with basal fT:C ratio (r = 0.63, p = 0.01). It is concluded that the
      differences in the training history and training specificity can be distinguished
      with regard to the MHC composition but not with regard to the basal T
      concentration. Simultaneously, it has been shown that MHC isoform content in
      human vastus lateralis muscle may be related to basal anabolic-catabolic hormone
      balance, and this hypothesis needs further investigation.

PMID- 22990574
TI  - Total energy expenditure assessment in elite junior basketball players: a
      validation study using doubly labeled water.
AB  - An accurate assessment of total energy expenditure (TEE) during a competitive
      season is required. We aimed to validate TEE estimated by self-reported energy
      intake (EI) and the dietary reference intake (DRI) method in 19 elite basketball
      players (aged 16-18 years) using doubly labeled water (DLW) as the reference
      method. The DRI models and EI from dietary records over a 7-day period were
      simultaneously assessed for TEE estimation. Resting energy expenditure was
      assessed by indirect calorimetry. Fat and fat-free mass (FFM) were determined by
      a 4-compartment model (body volume by air displacement plethysmography, bone
      mineral by DXA, and water by deuterium dilution). Fat and FFM ranged from 4 to 19
      kg and from 47 to 81 kg, respectively. The physical activity level ranged from
      2.2 to 3.7 with a mean value of 2.8 +/- 0.4. Total energy expenditure from DLW
      (17,598 +/- 3,298 kJ.d) was significantly underestimated by EI (11,274 +/- 2,567
      kJ.d), whereas no differences were found using DRI (17,008 +/- 3,206 kJ.d). The
      EI and DRI methods explained TEE from DLW by 34% (p = 0.057) and 44% (p = 0.002),
      respectively, and wide limits of agreement were observed. Our findings suggested
      that EI is not a valid tool for TEE assessment. The DRI method may be valid at a
      group level but inaccurate for estimating individual TEE in young players during
      a demanding competitive season period.

PMID- 22990575
TI  - Evaluation of a mobile shift report system on nursing documentation quality.
AB  - Nursing shift report is vital for patient care. Accordingly, healthcare
      facilities have made great efforts to establish a standardized nurse-to-nurse
      shift handoff process to ensure patient care quality. The purpose of this study
      was to determine whether the use of a standardized mobile intershift handoff
      system would affect the quality of nursing documentation. The study is based on
      nursing handoff records from 19 inpatient units in four major care areas
      (internal medicine, general surgery, obstetrics/pediatrics, and long-term care)
      of a medical center in central Taiwan. Data collection was performed before and
      after implementation of the mobile, point-of-care handoff system in 2010. A
      medical review tool was used to compare 25-item charting compliance on 228
      charts. Results show that the designed content of the handoff system was related
      to a corresponding compliance change in initial assessment, pain reassessment,
      and use of accurate abbreviation. Although overall compliance rates among
      inpatient units varied, the statistical test showed that the pattern of changes
      was consistent. As more items were added to the new handoff system for reminder
      purposes, documentation compliance increased; however, since the new handoff
      system did not include nursing diagnosis, patient outcome tracking compliance was
      reduced. The results of the study reveal that implementing a standardized point
      of-care handoff system could improve nursing documentation compliance and
      quality.

PMID- 22990576
TI  - Bioaccumulation and effects of perfluorinated compounds (PFCs) in zebra mussels
      (Dreissena polymorpha).
AB  - Perfluorinated chemicals (PFCs) have been used for many years in numerous
      industrial products and are known to accumulate in organisms. A recent survey
      showed that tissue levels of PFCs in aquatic organisms varied among compounds and
      species being undetected in freshwater zebra mussels Dreissena polymorpha. Here
      we studied the bioaccumulation kinetics and effects of two major PFCs,
      perfluorooctane sulfonic acid compound (PFOS) and perfluorooctanoic acid (PFOA),
      in multixenobiotic transporter activity (MXR) and filtration and oxygen
      consumption rates in zebra mussel exposed to a range of concentrations of a PCF
      mixture (1-1,000 MUg/L) during 10 days. Results indicate a low potential of the
      studied PFCs to bioaccumulate in zebra mussel tissues. PFCs altered mussel MXR
      transporter activity being inhibited at day 1 but not at day 10. Bioaccumulation
      kinetics of PFCs were inversely related with MXR transporter activity above 9
      ng/g wet weight and unrelated at tissue concentration lower than 2 ng/g wet
      weight suggesting that at high tissue concentrations, these type of compounds may
      be effluxed out by MXR transporters and as a result have a low potential to be
      bioaccumulated in zebra mussels. Oxygen consumption rates but not filtering rates
      were increased in all exposure levels and periods indicating that at
      environmental relevant concentrations of 1 MUg/L, the studied PFCs enhanced
      oxidative metabolism of mussels. Overall, the results obtained in this study
      confirm previous findings in the field indicating that an important fraction of
      PFC accumulated in mussel tissues is eliminated actively by MXR transporters or
      other processes that are metabolically costly.

PMID- 22990577
TI  - Polybrominated diphenyl ethers in surface sediments from principal watersheds of
      Shanghai, China: levels, distribution, influencing factors, and risk assessment.
AB  - Fourteen and 17 sediment samples were collected from three main rivers of
      Shanghai in July and November, respectively. Eight polybrominated diphenyl ether
      (PBDE) congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and
      BDE-209) were detected in these samples to clarify the pollution status in the
      metropolis. Instrumental analyses showed that the concentrations of ?8PBDEs
      ranged from 10.97 to 64.05 ng/g dry weight (dw), with an average value of 29.71
      ng/g dw. BDE-209 was the predominant congener accounting for more than 97% of
      total PBDEs, followed by BDE-47 and BDE-99. Remarkable spatial and seasonal
      distributions of PBDE concentrations were observed, suggesting that local
      sources, seasonal climates, and hydrologic conditions might be the influencing
      factors. Moderate correlations (r (2) = 0.28-0.51, p < 0.05) were found between
      total organic carbon and PBDEs, which indicated that organic carbon content
      influenced the distributions of PBDEs in sediment of Shanghai at some extent.
      Hazard quotients revealed PBDEs posed no potential risk to benthic organisms in
      the study area at present.

PMID- 22990579
TI  - Arsenic, chromium and mercury removal using mussel shell ash or a sludge/ashes
      waste mixture.
AB  - Different batches of valued mussel shell and waste mussel shell ash are
      characterised. Shell ash has pH > 12 and high electrical conductivities (between
      16.01 and 27.27 dS m(-1)), while calcined shell shows pH values up to 10.7 and
      electrical conductivities between 1.19 and 3.55 dS m(-1). X-ray fluorescence,
      nitric acid digestion and water extractions show higher concentrations in shell
      ash for most parameters. Calcite is the dominant crystalline compound in this ash
      (95.6%), followed by aragonite. Adsorption/desorption trials were performed for
      mussel shell ash and for a waste mixture including shell ash, sewage sludge and
      wood ash, showing the following percentage adsorptions: Hg(II) >94%, As(V) >96%
      and Cr(VI) between 11 and 30% for shell ash; Hg(II) >98%, As(V) >88% and Cr(VI)
      between 30 and 88% for the waste mixture. Hg and As desorption was <5% for both
      shell ash and the waste mixture, while Cr desorption was between 92 and 45% for
      shell ash, and between 19 and 0% for the mixture. In view of that, mussel shell
      ash and the mixture including shell ash, sewage sludge and wood ash could be
      useful for Hg(II) and As(V) removal.

PMID- 22990580
TI  - Functional assessment of intestinal motility and gut wall inflammation in
      rodents: analyses in a standardized model of intestinal manipulation.
AB  - Inflammation of the gastrointestinal tract is a common reason for a variety of
      human diseases. Animal research models are critical in investigating the complex
      cellular and molecular of intestinal pathology. Although the tunica mucosa is
      often the organ of interest in many inflammatory diseases, recent works
      demonstrated that the muscularis externa (ME) is also a highly immunocompetent
      organ that harbours a dense network of resident immunocytes.(1,2) These works
      were performed within the standardized model of intestinal manipulation (IM) that
      leads to inflammation of the bowel wall, mainly limited to the ME. Clinically
      this inflammation leads to prolonged intestinal dysmotility, known as
      postoperative ileus (POI) which is a frequent and unavoidable complication after
      abdominal surgery.(3) The inflammation is characterized by liberation of
      proinflammatory mediators such as IL-6(4) or IL-1beta or inhibitory
      neurotransmitters like nitric oxide (NO).(5) Subsequently, tremendous numbers of
      immunocytes extravasate into the ME, dominated by polymorphonuclear neutrophils
      (PMN) and monocytes and finally maintain POI.(2) Lasting for days, this
      intestinal paralysis leads to an increased risk of aspiration, bacterial
      translocation and infectious complications up to sepsis and multi organ failure
      and causes a high economic burden.(6) In this manuscript we demonstrate the
      standardized model of IM and in vivo assessment of gastrointestinal transit (GIT)
      and colonic transit. Furthermore we demonstrate a method for separation of the ME
      from the tunica mucosa followed by immunological analysis, which is crucial to
      distinguish between the inflammatory responses in these both highly immunoactive
      bowel wall compartments. All analyses are easily transferable to any other
      research models, affecting gastrointestinal function.

PMID- 22990578
TI  - The impact of the waterborne transmission of Toxoplasma gondii and analysis
      efforts for water detection: an overview and update.
AB  - The ubiquitous protozoa Toxoplasma gondii is now the subject of renewed interest,
      due to the spread of oocysts via water causing waterborne outbreaks of
      toxoplasmosis in different parts of the world. This overview discusses the
      different methods for detection of Toxoplasma in drinking and environmental
      water. It includes a combination of conventional and molecular tools for
      effective oocyst recovery and detection in water sources as well as factors
      hindering the detection of this parasite and shedding light on a promising new
      molecular assay for the diagnosis of Toxoplasma in environmental samples.
      Hopefully, this attempt will facilitate future approaches for better recovery,
      concentration, and detection of Toxoplasma oocysts in environmental waters.

PMID- 22990581
TI  - Lamina cribrosa thickness is not correlated with central corneal thickness or
      axial length in healthy eyes: central corneal thickness, axial length, and lamina
      cribrosa thickness.
AB  - BACKGROUND: The aim of this study was to determine the relationship of the
      central corneal thickness (CCT) and axial length (AXL) with the central lamina
      cribrosa thickness (LCT) in healthy human eyes. METHODS: This was a prospective
      observational case series. The optic discs of 189 eyes from 100 healthy subjects
      with a refractive error smaller than -8 diopters were scanned using enhanced
      depth imaging spectral-domain optical coherence tomography (Spectralis OCT,
      Heidelberg Engineering, Heidelberg, Germany). The thickness of the lamina
      cribrosa (LC) was measured on B-scan images obtained at the center of the optic
      nerve head. A linear mixed-effects model was used to determine the factors
      associated with LCT, taking into account clustering of eyes within subjects.
      RESULTS: The thickness of the central LC was 273.19 +/- 34.74 MUm (mean +/- SD;
      range, 173.73-367.94 MUm). Multivariate analysis revealed a significant influence
      of older age on increased central LCT (p = 0.001). There was no significant
      association between central LCT and either CCT or AXL. CONCLUSIONS: In this
      study, the central LCT increased significantly with older age in healthy human
      eyes. Neither CCT nor AXL was significantly associated with the central LCT in
      healthy human eyes with a spherical equivalent within the range from -7.0 to +3.0
      diopters.

PMID- 22990582
TI  - Taxonomy and chemically semi-defined media for the analysis of the tacrolimus
      producer 'Streptomyces tsukubaensis'.
AB  - 'Streptomyces tsukubaensis' was the first tacrolimus producer strain identified.
      Although it has been included in the Streptomyces genus, its taxonomic position
      has not been rigorously determined. By using a polyphasic approach, we have
      established that the tacrolimus producer strain 'S. tsukubaensis' NRRL 18488
      represents a unique species in the Streptomyces genus, which is phylogenetically
      distant from other subsequently described producers. This fact means a horizontal
      transference of the tacrolimus-producing gene cluster. Physiology, nutrient
      requirement, and molecular genetics analyses of tacrolimus biosynthesis in 'S.
      tsukubaensis' necessitate chemically defined or semi-defined media, which work as
      a jigsaw puzzle and allow for pieces (nutrients) exchange. To date, studies
      related to 'S. tsukubaensis' have been mainly focused in the improvement of
      tacrolimus production using complex industrial fermentation media, which
      difficulty allows testing of tacrolimus overproduction enhancers or inhibitors
      because of the presence of non-defined substances. In the present work, two semi
      defined media were developed in order to study the main factors involved in
      tacrolimus production in 'S. tsukubaensis'.

PMID- 22990584
TI  - Abstracts of the Neurocritical Care Society 10th Annual Meeting. October 4-7,
      2012. Denver, Colorado, USA.

PMID- 22990585
TI  - MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic
      Potential.
AB  - : Mesenchymal stromal/stem cells (MSC) are adult multipotent progenitors with
      fibroblast-like morphology able to differentiate into adipocytic, osteogenic,
      chondrogenic, and myogenic lineages. Due to these properties, MSC have been
      studied and introduced as therapeutics in regenerative medicine. Preliminary
      studies have also shown a possible involvement of MSC as precursors of cellular
      elements within tumor microenvironments, in particular tumor-associated
      fibroblasts (TAF). Among a number of different possible origins, TAF may
      originate from a pool of circulating progenitors from bone marrow or adipose
      tissue-derived MSC. There is growing evidence to corroborate that cells
      immunophenotypically defined as MSC are able to reside as TAF influencing the
      tumor microenvironment in a potentially bi-phasic and obscure manner: either
      promoting or inhibiting growth depending on tumor context and MSC sources. Here
      we focus on relationships between the tumor microenvironment, cancer cells, and
      MSC, analyzing their diverse ability to influence neoplastic development.
      Associated activities include MSC homing driven by the secretion of various
      mediators, differentiation towards TAF phenotypes, and reciprocal interactions
      with the tumor cells. These are reviewed here with the aim of understanding the
      biological functions of MSC that can be exploited for innovative cancer therapy. 

PMID- 22990583
TI  - Characterization of a novel beta-agarase from an agar-degrading bacterium
      Catenovulum sp. X3.
AB  - An agar-degrading bacterium, Catenovulum sp. X3, was isolated from the seawater
      of Shantou, China. A novel beta-agarase gene agaXa was cloned from the strain
      Catenovulum sp. X3. The gene agaXa consists of 1,590 bp and encodes a protein of
      529 amino acids, with only 40 % amino acid sequence identity with known agarases.
      AgaXa should belong to the glycoside hydrolase family GH118 based on the amino
      acid sequence similarity. The molecular mass of the recombinant AgaXa (rAgaXa)
      was estimated to be 52 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. It had a maximal agarase activity at 52  degrees C and pH 7.4
      and was stable over pH 5.0 ~ 9.0 and at temperatures below 42  degrees C. The K m
      and V max for agarose were 10.5 mg/ml and 588.2 U/mg, respectively. The purified
      rAgaXa showed endolytic activity on agarose degradation, yielding
      neoagarohexaose, neoagarooctaose, neoagarodecaose, and neoagarododecaose as the
      end products. The results showed that AgaXa has potential applications in agar
      degradation for the production of oligosaccharides with various bioactivities.

PMID- 22990586
TI  - Interface engineering for high-performance organic field-effect transistors.
AB  - The performance of organic field-effect transistors (OFETs) depends not only on
      the properties of organic semiconductors, gate dielectrics and electrodes, but it
      is also determined by the nature of the contact interfaces between the different
      functional components. Therefore, interface engineering to optimize the contacts
      becomes critically important for the fabrication of high performance OFETs. In
      this Perspective, representative strategies of interface engineering and the
      basic requirements for different functional components to enable high performance
      OFETs are highlighted.

PMID- 22990587
TI  - Phenotypic plasticity and integration in the mangrove rivulus (Kryptolebias
      marmoratus): a prospectus.
AB  - The mangrove rivulus (Kryptolebias marmoratus) is a small fish native to mangrove
      ecosystems in Florida, the Caribbean, Central America, and South America. This
      species is one of only two self-fertilizing, hermaphroditic vertebrates capable
      of producing offspring that are genetically identical to both the parent and all
      siblings. Long bouts of selfing result in individuals with completely homozygous
      genotypes, effectively allowing for the production of "clones." Rivulus is also
      extremely sensitive to environmental change, both during development and
      adulthood. Life-history traits, behavior, physiology, morphology, and even sexual
      phenotype are shaped to a large extent by the interaction of genes with the
      environment, and many of these traits appear to co-vary. True reaction norms can
      be generated for this species in much the same way as has been done for clonally
      reproducing invertebrates and plants that have contributed immensely to our
      understanding of the evolution of phenotypic plasticity. That is, rivulus
      provides the opportunity to place individuals with identical genotypes in many
      different environments at any point during ontogeny or adulthood. In addition,
      rivulus populations are characterized by high genotypic diversity, a luxury not
      afforded by many clonal vertebrates, which allows us to evaluate variation among
      genotypes in the shape of reaction norms and in patterns of covariance among
      traits. We provide background information on phenotypic plasticity and phenotypic
      integration, coupled with a description of characteristics that we feel qualify
      rivulus as a potentially powerful model in which to study the evolution of
      reaction norms and covariance among traits.

PMID- 22990589
TI  - "Light-tagged" bacteriophage as a diagnostic tool for the detection of
      phytopathogens.
AB  - Detection of the phytopathogen Pseudomonas cannabina pv alisalensis, the causal
      agent of bacterial blight of crucifers is essential for managing this disease. A
      phage-based diagnostic assay was developed that detects and identifies P.
      cannabina pv alisalensis from cultures and diseased plant specimens. A
      recombinant "light-tagged" reporter phage was generated by integrating the luxAB
      genes into the P. cannabina pv alisalensis phage PBSPCA1 genome. PBSPCA1::luxAB
      is viable, stable and detects P. cannabina pv alisalensis within minutes and with
      high sensitivity by conferring a bioluminescent signal. Detection is dependent on
      cell viability since cells treated with a bactericidal disinfectant are unable to
      elicit a signal. Importantly, the reporter phage detects P. cannabina pv
      alisalensis from diseased plant specimens indicating the potential of the
      diagnostic for disease identification. The reporter phage displays promise for
      the rapid and specific diagnostic detection of cultivated isolates, and infected
      plant specimens.

PMID- 22990588
TI  - An efficient expression and purification strategy for the production of S100
      proteins in Escherichia coli.
AB  - S100 proteins belong to a family of small, acidic, EF-hand Ca ( 2+) -binding
      proteins and have been found to exert both intracellular and extracellular
      functions in regulation of Ca ( 2+)  homeostasis, cytoskeletal dynamics, cell
      cycle, motility and differentiation. As a result, they have been widely
      investigated for their association with diseases, such as, neurological diseases,
      cardiomyopathy, neoplasias and inflammatory diseases. To facilitate further
      studies of S100 proteins, we reported a simple and efficient method for the
      expression and purification of human S100A4 and S100A11 proteins in Escherichia
      coli. Since S100 proteins share many common physical and chemical
      characteristics, we expect that this approach can be extended to the production
      of most S100 proteins.

PMID- 22990590
TI  - Serum thrombomodulin as a newly identified biomarker for postoperative lung
      injury: a prospective observational study.
AB  - Postoperative lung injury after lung cancer resection is still a difficult
      problem to be solved.  Thrombomodulin (TM) is a membrane-bound glycoprotein of
      endothelial cells, and its serum level is elevated in patients with acute lung
      injury or acute respiratory distress syndrome.  In fact, TM is abundant in the
      pulmonary capillary vessels.  Lung resection reduces the volume of pulmonary
      capillary vessels; however, the change in the serum levels of TM after lung
      resection remains to be investigated.  We therefore analyzed the postoperative
      changes in the serum TM levels in 60 patients who underwent thoracotomy without
      lung resection (n = 3), partial resection of the lung (n = 15), or lobectomy (n =
      42).  Preoperative and postoperative day-1 laboratory data including the serum
      levels of TM and KL-6, a sialylated carbohydrate antigen (a biomarker for
      pulmonary fibrosis), and oxygenation index were collected.  Unexpectedly, the
      postoperative serum levels of TM were lower than preoperative values in lobectomy
      group, whereas they remained unchanged after thoracotomy without lung resection
      and after partial resection of the lung.  In addition, the serum TM level
      decreased proportional to the resected lung volume.  Eight out of 42 patients
      with lobectomy presented high postoperative serum levels of TM, and 3 out of
      these 8 patients presented postoperative impaired oxygenation.  Postoperative
      impaired oxygenation occurred only in patients with elevated TM levels; namely,
      an increase of serum TM is associated with impaired oxygenation after lung
      resection.  In conclusion, serum TM is a possible biomarker for predicting the
      occurrence of postoperative lung injury.

PMID- 22990593
TI  - Physical studies of heterometallic rings: an ideal system for studying
      magnetically-coupled systems.
AB  - Heterometallic rings of general formula [Cat][M(7)M'F(8)(O(2)C(t)Bu)(8)] (M = a
      trivalent metal, M' = a divalent metal, cat = a secondary ammonium cation,
      caesium or rubidium) contain an octagon of metal centres with each metal-metal
      edge bridged by a fluoride and two carboxylates. The rings when M = Cr(III) give
      remarkably beautiful EPR and INS spectra, and allow us to examine new techniques.
      Use of these techniques allows us to study the models used to describe magnetic
      behaviour in exchange coupled systems. In this tutorial review we discuss the two
      main approaches to modelling magnetic data - the strong exchange limit and the
      microscopic Hamiltonian approaches, aiming to explain the major differences
      between the two approaches. We also describe some more esoteric measurements and
      theories.

PMID- 22990592
TI  - Dynamic modulation of an orientation preference map by GABA responsible for age
      related cognitive performance.
AB  - Accumulating evidence suggests that cognitive declines in old (healthy) animals
      could arise from depression of intracortical inhibition, for which a decreased
      ability to produce GABA during senescence might be responsible. By simulating a
      neural network model of a primary visual cortical (V1) area, we investigated
      whether and how a lack of GABA affects cognitive performance of the network:
      detection of the orientation of a visual bar-stimulus. The network was composed
      of pyramidal (P) cells and GABAergic interneurons such as small (S) and large (L)
      basket cells. Intrasynaptic GABA-release from presynaptic S or L cells
      contributed to reducing ongoing-spontaneous (background) neuronal activity in a
      different manner. Namely, the former exerted feedback (S-to-P) inhibition and
      reduced the frequency (firing rate) of action potentials evoked in P cells. The
      latter reduced the number of saliently firing P cells through lateral (L-to-P)
      inhibition. Non-vesicular GABA-release, presumably from glia and/or neurons, into
      the extracellular space reduced the both, activating extrasynaptic GABAa
      receptors and providing P cells with tonic inhibitory currents. By this
      combinatorial, spatiotemporal inhibitory mechanism, the background activity as
      noise was significantly reduced, compared to the stimulus-evoked activity as
      signal, thereby improving signal-to-noise (S/N) ratio. Interestingly, GABA
      spillover from the intrasynaptic cleft into the extracellular space was effective
      for improving orientation selectivity (orientation bias), especially when
      distractors interfered with detecting the bar-stimulus. These simulation results
      may provide some insight into how the depression of intracortical inhibition due
      to a reduction in GABA content in the brain leads to age-related cognitive
      decline.

PMID- 22990594
TI  - SIRT1 inhibits apoptosis of degenerative human disc nucleus pulposus cells
      through activation of Akt pathway.
AB  - Many studies have demonstrated that SIRT1, an NAD(+)-dependent deacetylase,
      reduces apoptosis in several different cells. However, the role of SIRT1 in
      apoptosis of disc nucleus pulposus (NP) cells remains unclear. The present study
      was performed to determine whether degenerative human NP would express SIRT1, and
      to investigate the role of SIRT1 in NP cells apoptosis. The expression of SIRT1
      in disc NP of patients (>55 years) with lumbar disc degenerative disease (DDD)
      and the disc NP of patients (<25 years) with lumbar vertebra fracture (LVF) was
      assessed by immunohistochemistry, reverse transcription polymerase chain
      reaction, and Western blot analysis. The results showed that SIRT1 mRNA and
      protein levels were greater in LVF disc NP than those in DDD disc NP.
      Degenerative human NP cells were treated in culture with activator or inhibitor
      of SIRT1, resveratrol or nicotinamide, or SIRT1 small interfering RNA (siRNA),
      and cell apoptosis was quantified via flow cytometry. The rate of apoptosis was
      far fewer in resveratrol-treated NP cells than in SIRT1 siRNA-transfected or
      nicotinamide-treated NP cells. After SIRT1 siRNA was transfected, NP cells
      decreased phosphorylation of Akt, while resveratrol phosphorylated Akt. Treatment
      with LY294002 or Akt siRNA increased the rate of apoptosis. Our results suggested
      that SIRT1 plays a critical role in survival of degenerative human NP cells
      through the Akt anti-apoptotic signaling pathway.

PMID- 22990595
TI  - Reelin promotes microtubule dynamics in processes of developing neurons.
AB  - The extracellular matrix protein reelin controls radial migration and layer
      formation of cortical neurons, in part by modulation of cytoskeletal dynamics. A
      stabilizing effect of reelin on the actin cytoskeleton has been described
      recently. However, it is poorly understood how reelin modulates microtubule
      dynamics. Here, we provide evidence that reelin increases microtubule assembly.
      This effect is mediated, at least in part, by promoting microtubule plus end
      dynamics in processes of developing neurons. Thus, we treated primary neuronal
      cultures with nocodazole to disrupt microtubules. After nocodazole washout, we
      found microtubule reassembly to be accelerated in the presence of reelin.
      Moreover, we show that reelin treatment promoted the formation of microtubule
      plus end binding protein 3 (EB3) comets in developing dendrites, and that EB3
      immunostaining in the developing wild-type neocortex is most intense in the
      reelin-rich marginal zone where leading processes of radially migrating neurons
      project to. This characteristic EB3 staining pattern was absent in reeler. Also
      reassembly of nocodazole-dispersed dendritic Golgi apparati, which are closely
      associated to microtubules, was accelerated by reelin treatment, though with a
      substantially slower time course when compared to microtubule reassembly. In
      support of our in vitro results, we found that the subcellular distribution of
      alpha-tubulin and acetylated tubulin in reeler cortical sections differed from
      wild-type and from mice lacking the very low density lipoprotein receptor
      (VLDLR), known to bind reelin. Taken together, our results suggest that reelin
      promotes microtubule assembly, at least in part, by increasing microtubule plus
      end dynamics.

PMID- 22990596
TI  - Dynamic expression of the sodium-vitamin C co-transporters, SVCT1 and SVCT2,
      during perinatal kidney development.
AB  - Isoform 1 of the sodium-vitamin C co-transporter (SVCT1) is expressed in the
      apical membrane of proximal tubule epithelial cells in adult human and mouse
      kidneys. This study is aimed at analyzing the expression and function of SVCTs
      during kidney development. RT-PCR and immunohistochemical analyses revealed that
      SVCT1 expression is increased progressively during postnatal kidney development.
      However, SVCT1 transcripts were barely detected, if not absent, in the embryonic
      kidney. Instead, the high-affinity transporter, isoform 2 (SVCT2), was strongly
      expressed in the developing kidney from E15; its expression decreased at
      postnatal stages. Immunohistochemical analyses showed a dynamic distribution of
      SVCT2 in epithelial cells during kidney development. In renal cortex tubular
      epithelial cells, intracellular distribution of SVCT2 was observed at E19 with
      distribution in the basolateral membrane at P1. In contrast, SVCT2 was localized
      to the apical and basolateral membranes between E17 and E19 in medullary kidney
      tubular cells but was distributed intracellularly at P1. In agreement with these
      findings, functional expression of SVCT2, but not SVCT1 was detected in human
      embryonic kidney-derived (HEK293) cells. In addition, kinetic analysis suggested
      that an ascorbate-dependent mechanism accounts for targeted SVCT2 expression in
      the developing kidney during medullary epithelial cell differentiation. However,
      during cortical tubular differentiation, SVCT1 was induced and localized to the
      apical membrane of tubular epithelial cells. SVCT2 showed a basolateral
      polarization only for the first days of postnatal life. These studies suggest
      that the uptake of vitamin C mediated by different SVCTs plays differential roles
      during the ontogeny of kidney tubular epithelial cells.

PMID- 22990597
TI  - CT arthrography of the wrist using a novel, mobile, dedicated extremity cone-beam
      CT (CBCT).
AB  - PURPOSE: To evaluate the feasibility and intra- and interobserver agreement of
      CBCT arthrography of wrist ligaments, triangular fibrocartilaginous complex
      (TFCC), and to assess the sensitivity (SE), specificity (SP), accuracy (ACC), and
      positive and negative predictive value (PPV, NPV) of CBCT arthrography in the
      diagnosis of scapholunate (SLL) and lunotriquetral (LTL) ligament tears, TFCC,
      and cartilage abnormalities of the scaphoid and lunate with their corresponding
      radial surfaces (scaphoid and lunate fossa) using a novel, mobile, dedicated
      extremity CBCT scanner. MATERIALS AND METHODS: Fifty-two consecutively enrolled
      subjects (26 M, 26 F, mean age 38 years, range 18-66 years) with suspected wrist
      ligament tears underwent CBCT-arthrography before normally scheduled MR
      arthrography.An extremity CBCT was used for imaging with isotropic voxel size of
      0.4 * 0.4 * 0.4 mm(3). Subsequent routine 1.5 T MRI was performed using a
      dedicated wrist coil.Two observers reviewed the anonymized CBCT images twice for
      contrast enhancement (CE) and technical details (TD), for tears of the SLL, LTL,
      and TFCC. Also, cartilage abnormalities of the scaphoid and lunate with their
      corresponding radial surfaces (scaphoid and lunate fossa) were evaluated. Inter-
      and intraobserver agreement was determined using weighted kappa statistics. Since
      no surgery was performed, MRI served as a reference standard, and SE and SP, ACC,
      PPV, and NPV were calculated. RESULTS: Intra- and interobserver kappa values for
      both readers (reader 1/reader 2; first reading/second reading) with 95 %
      confidence limits were: CE 0.54 (0.08-1.00)/ 0.75 (0.46-1.00); 0.73 (0.29-1.00)/
      0.45 (0.07-0.83), TD 0.53 (0.30-0.88)/ 0.86 (0.60-1.00); 0.56 (0.22-0.91)/ 0.67
      (0.37-0.98), SLL 0.59 (0.25-0.93)/ 0.66 (0.42-0.91); 0.31 (0.06-0.56)/ 0.49 (0.26
      0.73), LTL 0.83 (0.66-1.00)/ 0.68 (0.46-0.91); 0.90 (0.79-1.00)/ 0.48 (0.22
      0.74); TFCC (0.72-1.00)/ (0.79-1.00); 0.65 (0.43-0.87)/ 0.59 (0.35-0.83), radius
      (scaphoid fossa) 0.45 (0.12-0.77)/ 0.64 (0.31-0.96); 0.58 (0.19-0.96)/ 0.38 (0.09
      0.66), scaphoid 0.43 (0.12-0.74)/ 0.76 (0.55-0.96); 0.37 (0.00-0.75)/ 0.32 (0.04
      0.59), radius (lunate fossa) 0.68 (0.36-1.00)/ 0.42 (0.00-0.86); 0.62 (0.29
      0.96)/ 0.51 (0.12-0.91), and lunate 0.53 (0.16-0.90)/ 0.68 (0.44-0.91); 0.59
      (0.29-0.88)/ 0.42 (0.00-0.84), respectively. The overall mean accuracy was 82-92
      % and specificity was 81-94 %. Sensitivity for LTL and TFCC tears was 76-83, but
      for SLL tears it was 58 %. For cartilage abnormalities, the accuracy and negative
      predictive value were high, 90-98 %. CONCLUSIONS: A dedicated CBCT extremity
      scanner is a new method for evaluating the wrist ligaments and radiocarpal
      cartilage. The method has an overall accuracy of 82-86 % and specificity 81-91 %.
      For cartilage abnormalities, the accuracy and negative predictive value were
      high.

PMID- 22990598
TI  - Inferring evoked brain connectivity through adaptive perturbation.
AB  - Inference of functional networks-representing the statistical associations
      between time series recorded from multiple sensors-has found important
      applications in neuroscience. However, networksexhibiting time-locked activity
      between physically independent elements can bias functional connectivity
      estimates employing passive measurements. Here, a perturbative and adaptive
      method of inferring network connectivity based on measurement and stimulation-so
      called "evoked network connectivity" is introduced. This procedure, employing a
      recursive Bayesian update scheme, allows principled network stimulation given a
      current network estimate inferred from all previous stimulations and recordings.
      The method decouples stimulus and detector design from network inference and can
      be suitably applied to a wide range of clinical and basic neuroscience related
      problems. The proposed method demonstrates improved accuracy compared to network
      inference based on passive observation of node dynamics and an increased rate of
      convergence relative to network estimation employing a naive stimulation
      strategy.

PMID- 22990599
TI  - Oxomolybdenum monodithiolene complexes linked with sulfur bridged iron:
      antiferromagnetically coupled Fe(III)Mo(V) systems.
AB  - Mo-Fe heterometallic complexes with Fe(X)(2) (X = Cl, SPh) moiety attached to
      monodithiolene oxomolybdenum via sulfur bridge, viz.,
      [Ph(4)P](2)[Cl(2)FeS(2)MoOS(2)(DMED)] (2) (DMED, dimethylethylenedicarboxylate),
      [Ph(4)P](2)[Cl(2)FeS(2)MoO(tdt)] (3) (tdt, toluenedithiolate) and
      [Ph(4)P](2)[(SPh)(2)FeS(2)MoO(tdt)] (4) are reported. Mossbauer spectroscopy,
      magnetism, EPR, electrochemistry and electronic structure based on DFT and TD-DFT
      calculation show the transfer of electron from iron to molybdenum centre
      resulting antiferromagnetically coupled Fe(III)Mo(V) unit from the starting
      Fe(II) and Mo(VI) compounds. A net spin of S = 2 ground state arising from
      antiferromagnetically coupled Fe(III) and Mo(V) shows a rare X-band EPR in normal
      mode at g ~ 12 in the solid state. In addition, Mossbauer studies show that
      electron drifting is more pronounced upon substitution of the chloride ligand by
      thiophenolate. The changes in dithiolene periphery electronically affect the
      charge distribution between Mo-Fe in {OMo(MUS)(2)Fe} core. DFT calculations
      indicate that the increasing stability of dative Fe -> Mo hetero metal-metal bond
      in these complexes from 3 to 2 to 4 is related to the extent of electron transfer
      from the iron to molybdenum centre.

PMID- 22990600
TI  - Apis mellifera pollination improves agronomic productivity of anemophilous castor
      bean (Ricinus communis).
AB  - Castor bean (Ricinus communis L.) is cultivated mainly for biodiesel production
      because of its oil-rich seeds; it is assumed to be an anemophylous species. But
      pollination deficit can lead to low productivity often attributed to other
      reasons. In this paper, we investigated pollination requirements, pollination
      mechanism, occurrence of pollination deficit, and the role of biotic pollinators
      in a large commercial plantation of castor bean. Our results show that R.
      communis bears a mixed breeding system favoring selfing by geitonogamy, although
      the wind promotes mostly outcrossing. We also found that the honey bee (Apis
      mellifera L.) foraging on castor bean can both transfer pollen from male to
      female flowers within the same raceme and boost the release of airborne pollen by
      male flowers. Both situations increase geitonogamy rates, raising significantly
      fruit set and seed yield. This is the first report of an animal foraging activity
      increasing seed yield in an anemophilous and geitonogamous crop and elucidates
      the role of biotic pollinators in castor bean reproduction.

PMID- 22990601
TI  - Acute toxicity of sodium metabisulphite on mangrove crab Ucides cordatus
      (Decapoda, Ucididae).
AB  - The sodium metabisulphite salt is usually used in shrimp culture to prevent black
      spot. Unfortunately the toxicological effect of this xenobiotic in decapod crabs
      is unknown. Thus, the present study aims to investigate the sodium metabisulphite
      LC(50) - 96 h in the mangrove species Ucides cordatus. Crabs were collected in
      the tidal creek margins in Braganca estuarine and were submitted to preliminary
      test (screening) and posterior definitive test. Crabs were exposed in five
      different concentrations and a control group in five replicates, two crabs per
      recipient (5 L) during 96 hours. A negative correlation was observed to sodium
      metabisulphite concentration in relation to dissolved oxygen and pH. At the end
      of the experiment were obtained the following mortality index in relation to
      sodium metabisulphite concentrations: 100% in 86.0 mg.L(-1), 74% in 62.0 mg.L(
      1), 52% in 52.0 mg.L(-1), 44% in 38.0 mg.L(-1). The value of LC(50) - 96 h for U.
      cordatus was determinate at 42.58 mg.L(-1)/Na(2)S(2)O(5). The results strongly
      indicate that sodium metabisulphite is toxic for U. cordatus, and this crab could
      be used for biomonitoring the environmental impact.

PMID- 22990602
TI  - Toxicity of Neem's oil, a potential biocide against the invasive mussel
      Limnoperna fortunei (Dunker 1857).
AB  - The golden mussel Limnoperna fortunei (Dunker 1857) is one of the most
      distributed Nuisance Invasive Species (NIS) in South America, and a threat of
      great concern for the industry of the area. In this study, we carried out
      toxicity tests made with a Neem's oil solution with L. fortunei larvae and
      benthonic adults (7, 13 and 19 +/- 1 mm). Tests with non-target species (Daphnia
      magna, Lactuca sativa and Cnesterodon decemmculatus) were also made with the aim
      to evaluate the potential toxicity of the Neem's solution in the environment. The
      LC(100) of Neem's solution obtained for larvae was 500 ul/L, a value much higher
      than the one obtained for D. magna and C. decemmaculatus. Thus, we recommend that
      it should not be used in open waters. However, since the adults were killed in 72
      h and the larvae in 24 h, this product can be used in closed systems, in man-made
      facilities.

PMID- 22990603
TI  - Use of fishing resources by women in the Mamanguape River Estuary, Paraiba state,
      Brazil.
AB  - We evaluated the appropriation and use of fishing resources by women residing
      near the Mamanguape River Estuary (MRE), Paraiba state, Brazil. Were used
      combinations of qualitative (interviews and direct observations) and quantitative
      methods (use value and corrected principal use concordance). Thirty women were
      interviewed and reported the use of 41 species (30 fish, 8 crustaceans, and 3
      mollusks), mainly for local consumption and sale. The species with the highest
      use value were Genidens genidens (0.7), Callinectes exasperatus (0.73) and
      Anomalocardia brasiliana (0.46). The diversity of resources exploited
      demonstrates the importance of the mangrove ecosystem to MRE families, and the
      data gathered can serve as a basis for formulating public policies to promote the
      equal participation of women in fishing and environmental conservation.

PMID- 22990604
TI  - Modeling colitis-associated cancer with azoxymethane (AOM) and dextran sulfate
      sodium (DSS).
AB  - Individuals with inflammatory bowel disease (IBD), such as Crohn's disease (CD)
      or ulcerative colitis (UC) are at increased risk of developing colorectal cancer
      (CRC) over healthy individuals. This risk is proportional to the duration and
      extent of disease, with a cumulative incidence as high as 30% in individuals with
      longstanding UC with widespread colonic involvement. Colonic dysplasia in IBD and
      colitis associated cancer (CAC) are believed to develop as a result of repeated
      cycles of epithelial cell injury and repair while these cells are bathed in a
      chronic inflammatory cytokine milieu. While spontaneous and colitis-associated
      cancers share the quality of being adenocarcinomas, the sequence of underlying
      molecular events is believed to be different. This distinction argues the need
      for specific animal models of CAC. Several mouse models currently exist for the
      study of CAC. Dextran sulfate sodium (DSS), an agent with direct toxic effects on
      the colonic epithelium, can be administered in drinking water to mice in multiple
      cycles to create a chronic inflammatory state. With sufficient duration, some of
      these mice will develop tumors. Tumor development is hastened in this model if
      administered in a pro-carcinogenic setting. These include mice with genetic
      mutations in tumorigenesis pathways (APC, p53, Msh2), as well as mice pre-treated
      with genotoxic agents (azoxymethane [AOM], 1,2-dimethylhydrazine [DMH]). The
      combination of DSS with AOM as a model for colitis associated cancer has gained
      popularity for its reproducibility, potency, low price, and ease of use. Though
      they have a shared mechanism, AOM has been found to be more potent and stable in
      solution than DMH. While tumor development in other models generally requires
      several months, mice injected with AOM and subsequently treated with DSS develop
      adequate tumors in as little as 7-10 weeks. Finally, AOM and DSS can be
      administered to mice of any genetic background (knock out, transgenic, etc.)
      without cross-breeding to a specific tumorigenic strain. Here, we demonstrate a
      protocol for inflammation-driven colonic tumorigenesis in mice utilizing a single
      injection of AOM followed by three seven-day cycles of DSS over a 10 week period.
      This model induces tumors with histological and molecular changes closely
      resembling those occurring in human CAC and provides a highly valuable model for
      the study of oncogenesis and chemoprevention in this disease.

PMID- 22990605
TI  - Postoperative pharyngocutaneous fistula: treated by sternocleidomastoid flap
      repair and cricopharyngeus myotomy.
AB  - INTRODUCTION: Pharyngoesophagocutaneous fistula (PEF) is one of the rare but
      serious complications of antero-lateral approach to cervical spine surgery.
      Because of its rarity, the true incidence of PEF is not clear. But, retrospective
      analysis of large series of cervical spine surgery reports 0-1.62 % incidence
      (Cloward in Surg 69:175-182, 1971; Elerkay et al. in J Neurosurg Spine 90(Suppl
      1):35-41, 1999). Proximity to the vertebral column and thin walls makes the upper
      digestive tract vulnerable to injury in cervical trauma, surgical or nonsurgical.
      Presentation in early postoperative period is not rare and carries high morbidity
      and mortality (Jones and Ginsberg in Ann Thorac Surg 53(3):534-543, 1992).
      Various procedures for these fistulae such as simple closure, muscle flap
      interposition, esophageal diversion and jejunal interposition are reported. Some
      authors also advise removal of prosthetic plates and posterior stabilization,
      besides the repair of fistulae in a staged manner (Orlando et al. in Spine
      28(15):E290-E295, 2003). METHODS: Two similar cases of pharyngeal fistulae with
      similar etiology and clinical scenario are presented here, which were managed
      successfully with initial control of sepsis followed by delayed definitive repair
      with sternocleidomastoid muscle flap interposition and cricopharyngeus myotomy
      without removal of prosthetic plates. RESULTS: Postoperatively, both patients
      showed no evidence of any wound complications or collections until the seventh
      day. A contrast swallow study on seventh day showed no leak following which soft
      diet was started. Both patients were not having any difficulty in swallowing or
      aspiration. On 1-year follow-up, both patients were having no difficulty in
      swallowing, no episodes of aspiration and no recurrence of fistula. CONCLUSION:
      This case series highlights the importance of cricopharyngeus myotomy for
      treating PEF and the improved results with the prosthesis kept undisturbed.

PMID- 22990606
TI  - Tandem age-related lumbar and cervical intervertebral disc changes in
      asymptomatic subjects.
AB  - PURPOSE: To investigate the frequency of tandem lumbar and cervical
      intervertebral disc degeneration in asymptomatic subjects. METHODS: We evaluated
      magnetic resonance imaging (MRI) results from 94 volunteers (48 men and 46 women;
      mean age 48 years) for age-related intervertebral disc degeneration in the lumbar
      and cervical spine. RESULTS: MRI indicated degenerative changes in the lumbar
      spine in 79 subjects (84 %), with decreased disc signal intensity in 74.5 %,
      posterior disc protrusion in 78.7 %, anterior compression of the dura in 81.9 %,
      disc space narrowing in 21.3 %, and spinal canal stenosis in 12.8 %. These
      findings were more common in older subjects at caudal levels. MRI showed
      degenerative changes in both the lumbar and cervical spine in 78.7 % of the
      volunteers. CONCLUSIONS: Degenerative findings in both the lumbar and cervical
      spine, suggesting tandem disc degeneration, was common in asymptomatic subjects.
      These results provide normative data for evaluating patients with degenerative
      lumbar and cervical disc diseases.

PMID- 22990607
TI  - [Long-term outcome after cholecystectomy-related biliary and vasculobiliary
      injuries].

PMID- 22990608
TI  - [Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for
      peritoneal metastasized gastric cancer].

PMID- 22990609
TI  - Roughening of hcp metal surfaces induced by nitrogen adsorption.
AB  - Using DFT calculations and thermodynamic considerations, the structure of Ru, Os,
      and Re hcp(1121) surfaces has been studied in the presence of a N(2) atmosphere.
      We find that N adsorption causes two-sided ridges consisting of hcp{1342} faces
      to form on the initially planar hcp(1121) surface. The rough hcp(1342) surface
      has a high density of low-coordinated atoms and is expected to show a high bond
      breaking activity. Since the roughening of hcp(1121) is also favorable at
      elevated temperatures and pressures, it might be capable to change the activity
      of the hcp-catalysts.

PMID- 22990610
TI  - Time for children: trends in the employment patterns of parents, 1967-2009.
AB  - Using data from the 1967-2009 years of the March Current Population Surveys
      (CPS), we examine two important resources for children's well-being: time and
      money. We document trends in parental employment, from the perspective of
      children, and show what underlies these trends. We find that increases in family
      work hours mainly reflect movements into jobs by parents-particularly mothers,
      who in prior decades would have remained at home. This increase in market work
      has raised incomes for children in the typical two-parent family but not for
      those in lone-parent households. Time use data from 1975 and 2003-2008 reveal
      that working parents spend less time engaged in primary childcare than their
      counterparts without jobs but more than employed peers in previous cohorts.
      Analysis of 2004 work schedule data suggests that non-daytime work provides an
      alternative method of coordinating employment schedules for some dual-earner
      families.

PMID- 22990612
TI  - Mammalian protein expression noise: scaling principles and the implications for
      knockdown experiments.
AB  - The abundance of a particular protein varies both over time within a single
      mammalian cell and between cells of a genetically identical population. Here, we
      investigate the properties of such noisy protein expression in mammalian cells by
      combining theoretical and experimental approaches. The gamma distribution model
      is well-known to describe cell-to-cell variability in protein expression in a
      variety of common scenarios. This model predicts, and experiments show, that when
      protein levels are manipulated by altering transcription rates or mRNA half-life,
      protein expression noise, defined as the squared coefficient of variation, is
      constant. In contrast, we also demonstrate that when protein levels are
      manipulated by changing protein half-life, as mean levels increase, noise
      decreases. Thus, in mammalian cells, the scaling relationship between mean
      protein levels and expression noise depends on how mean levels are perturbed.
      Therefore it may be important to consider how common experimental manipulations
      of protein expression affect not only mean levels, but also noise levels. In the
      context of knockdown experiments, natural cell-to-cell variability in protein
      expression implies that a particular cell from the knockdown population may have
      higher protein levels than a cell from the control population. Simulations and
      experimental data suggest that approximately three-fold knockdown in mean
      expression levels can reduce such so-called "overlap probability" to less than
      ~10%. This has implications for the interpretation of knockdown experiments when
      the readout is a single cell measure.

PMID- 22990613
TI  - The incidence of oropharyngeal dysphagia in infants with GERD-like symptoms.
AB  - BACKGROUND: Symptoms of infantile gastroesophageal reflux disease (GERD) may
      overlap with oropharyngeal dysphagia, but the evaluation and treatment of these
      conditions vary greatly. In this investigation, the incidence of oropharyngeal
      dysphagia in infants with GERD-like symptoms is determined. MATERIALS AND
      METHODS: A retrospective chart review was performed on infants referred to a
      pediatric gastroenterology clinic for GERD-like symptoms. A feeding screen was
      performed in all infants. Standardized bedside swallow evaluation and modified
      barium swallow (MBS) studies were then performed when clinically indicated. A
      similarly aged cohort of normal participants also underwent a standard bedside
      swallow evaluation for group comparison. RESULTS: Study population included 67
      infants. A swallow evaluation was recommended in 39 of 67 infants with
      abnormalities noted in all. Swallowing abnormalities were more frequent and
      clustered in infants with GERD-like symptoms vs controls. MBS was abnormal in 16
      of 17 qualifying infants. Characteristics of at-risk infants included extreme
      prematurity, developmental delay, or symptoms refractory to antireflux
      medications. CONCLUSION: Oropharyngeal dysphagia is prominent in infants with
      GERD-like symptoms.

PMID- 22990614
TI  - Response to the letter to the editor regarding Nutrition support of neonatal
      patients at risk for necrotizing enterocolitis.

PMID- 22990615
TI  - Side effects of long-term glutamine supplementation.
AB  - Some people consume chronically glutamine (GLN) in high quantities (~40 g/d),
      although a number of biochemical pathways and cellular functions may be
      negatively affected. The following side effects of GLN supplementation are
      discussed: (1) Alterations in amino acid transport-as GLN shares the transporters
      with other amino acids, enhanced GLN intake may impair amino acid distribution
      among tissues and their absorption in the gut and kidneys. (2) Alterations in GLN
      metabolism-GLN supplementation may impair synthesis of endogenous GLN and enhance
      glutamate and ammonia production. (3) Alterations in ammonia transport-GLN
      supplementation may impair ammonia detoxification and negatively affect the role
      of GLN as the carrier of ammonia among tissues. (4) Abnormalities in
      aminoacidemia-increased plasma levels of GLN, glutamate, citrulline, ornithine,
      arginine, and histidine and decreased levels of valine, leucine, isoleucine,
      glycine, threonine, serine, and proline are reported. (5) Alterations in immune
      system-as GLN has immunomodulating properties, the effect of chronic GLN
      consumption on the immune system needs to be assessed. (6) Effect on tumor growth
      it should be elucidated whether chronic intake of GLN increases the risk of
      cancer. (7) Effect of the withdrawal of GLN supplementation-due to the adaptive
      response of the organism to enhanced GLN consumption, the withdrawal of GLN may
      enhance the risk of health problems resulting from GLN deficiency. It is
      concluded that enhanced intake of GLN has substantial side effects, and long-term
      studies should be performed to justify chronic consumption of a GLN-enriched
      diet. 

PMID- 22990616
TI  - One-year results of bevacizumab intravitreal and posterior sub-Tenon injection of
      triamcinolone acetonide with reduced laser fluence photodynamic therapy for
      retinal angiomatous proliferation.
AB  - PURPOSE: Our aim was to study the efficacy of combined triple therapy with
      intravitreal bevacizumab injections (IVB), posterior sub-Tenon injection of
      triamcinolone acetonide (STTA), and reduced laser fluence photodynamic therapy
      (RFPDT) in Japanese patients with retinal angiomatous proliferation (RAP).
      DESIGN: This was a retrospective, observational, consecutive case series.
      METHODS: Fifteen consecutive RAP treatment-naive eyes were treated with triple
      therapy of IVB, STTA, and RFPDT (25 J/cm(2) of laser fluence). Whenever there was
      a recurrence of retinal-retinal anastomosis (RRA) or retinal-choroidal
      anastomosis (RCA) and marked leakage from subretinal neovascularization, the
      triple therapy was reapplied. When there were only intraretinal exudative and/or
      hemorrhagic changes without distinct RRA or RCA, IVB alone was applied. RESULTS:
      The mean logarithm of the minimum angle of resolution (logMAR) best-corrected
      visual acuity (BCVA) at baseline improved significantly (from 0.489 to 0.294 12
      months) (paired t test, p = 0.043). LogMAR BCVA at 12 months was stable or
      improved by >= 0.2 in 14 eyes (93.3 %). Mean number of triple therapy instituted
      during the 12-month study period was 1.2, and mean number of IVB treatments was
      1.4. CONCLUSION: Combined IVB, STTA, and RFPDT for RAP was effective in
      maintaining or improving VA at 1 year. In addition, the number of treatments
      could be markedly reduced.

PMID- 22990617
TI  - Scaffolds for bone tissue engineering fabricated from two different materials by
      the rapid prototyping technique: PCL versus PLGA.
AB  - Three dimensional tissue engineered scaffolds for the treatment of critical
      defect have been usually fabricated by salt leaching or gas forming technique.
      However, it is not easy for cells to penetrate the scaffolds due to the poor
      interconnectivity of pores. To overcome these current limitations we utilized a
      rapid prototyping (RP) technique for fabricating tissue engineered scaffolds to
      treat critical defects. The RP technique resulted in the uniform distribution and
      systematic connection of pores, which enabled cells to penetrate the scaffold.
      Two kinds of materials were used. They were poly(epsilon-caprolactone) (PCL) and
      poly(D, L-lactic-glycolic acid) (PLGA), where PCL is known to have longer
      degradation time than PLGA. In vitro tests supported the biocompatibility of the
      scaffolds. A 12-week animal study involving various examinations of rabbit tibias
      such as micro-CT and staining showed that both PCL and PLGA resulted in
      successful bone regeneration. As expected, PLGA degraded faster than PCL, and
      consequently the tissues generated in the PLGA group were less dense than those
      in the PCL group. We concluded that slower degradation is preferable in bone
      tissue engineering, especially when treating critical defects, as mechanical
      support is needed until full regeneration has occurred.

PMID- 22990618
TI  - Quantitative proteomics reveals altered expression of extracellular matrix
      related proteins of human primary dermal fibroblasts in response to sulfated
      hyaluronan and collagen applied as artificial extracellular matrix.
AB  - Fibroblasts are the main matrix producing cells of the dermis and are also
      strongly regulated by their matrix environment which can be used to improve and
      guide skin wound healing processes. Here, we systematically investigated the
      molecular effects on primary dermal fibroblasts in response to high-sulfated
      hyaluronan [HA] (hsHA) by quantitative proteomics. The comparison of non- and
      high-sulfated HA revealed regulation of 84 of more than 1,200 quantified
      proteins. Based on gene enrichment we found that sulfation of HA alters
      extracellular matrix remodeling. The collagen degrading enzymes cathepsin K,
      matrix metalloproteinases-2 and -14 were found to be down-regulated on hsHA.
      Additionally protein expression of thrombospondin-1, decorin, collagen types I
      and XII were reduced, whereas the expression of trophoblast glycoprotein and
      collagen type VI were slightly increased. This study demonstrates that global
      proteomics provides a valuable tool for revealing proteins involved in molecular
      effects of growth substrates for further material optimization.

PMID- 22990621
TI  - T1/ST2 promotes T helper 2 cell activation and polyfunctionality in
      bronchopulmonary mycosis.
AB  - Interleukin (IL)-33 enhances T helper (Th)2 immunity via its receptor T1/ST2.
      Infection with the yeast-like pathogen Cryptococcus neoformans is usually
      controlled by a Th1-mediated immune response. The mechanisms responsible for
      nonprotective Th2 immunity leading to allergic inflammation in pulmonary
      cryptococcosis are still not fully understood. Using a murine pulmonary model of
      C. neoformans infection, we report that T1/ST2 expression correlates with the
      intensity of Th2 activation, as demonstrated by the expression of CD25 and CD44
      and downregulation of CD62L. Antigen-specific T1/ST2(+) Th cells are the primary
      source of the Th2 cytokines IL-5 and IL-13 as compared with wild-type T1/ST2(-)
      Th cells or Th cells from T1/ST2(-/-) mice. In addition, T1/ST2(+) Th cells
      almost exclusively contain bi- and trifunctional Th2 cytokine-producing Th cells
      compared with T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. Finally,
      T1/ST2-driven Th2 development resulted in defective pulmonary fungal control.
      These data demonstrate that T1/ST2 directs Th2 cell activation and
      polyfunctionality in allergic bronchopulmonary mycosis.

PMID- 22990619
TI  - Dextromethorphan attenuated inflammation and combined opioid use in humans
      undergoing methadone maintenance treatment.
AB  - Recent studies show that proinflammatory cytokines might be related to the
      development of opioid dependence (physiological, psychological, or both). In a
      double-blind, randomly stratified clinical trial investigating whether add-on
      dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of
      opioids in heroin-dependent patients undergoing methadone maintenance treatment,
      we evaluated whether inflammation is related to the progression of opioid
      dependence. All participants (107 heroin-dependent patients and 84 nondependent
      healthy controls) were recruited from National Cheng Kung University Hospital.
      Their plasma cytokine levels were measured to evaluate the effect of add-on
      dextromethorphan. Plasma TNF-alpha and IL-8 levels were significantly higher in
      long-term heroin-dependent patients than in healthy controls (p < 0.001). Chronic
      heroin-use-induced TNF-alpha and IL-8 levels were significantly (p < 0.05)
      attenuated in patients treated for 12 weeks with add-on dextromethorphan.
      Moreover, both tolerance to methadone and the combined use of opioids were
      significantly (p < 0.05) attenuated in patients taking dextromethorphan. We
      conclude that dextromethorphan might be a feasible adjuvant therapeutic for
      attenuating inflammation and inhibiting methadone tolerance and combined opioid
      use in heroin-dependent patients.

PMID- 22990622
TI  - Resident and pro-inflammatory macrophages in the colon represent alternative
      context-dependent fates of the same Ly6Chi monocyte precursors.
AB  - Macrophages (mphi) are essential for intestinal homeostasis and the pathology of
      inflammatory bowel disease (IBD), but it is unclear whether discrete mphi
      populations carry out these distinct functions or if resident mphi change during
      inflammation. We show here that most resident mphi in resting mouse colon express
      very high levels of CX3CR1, are avidly phagocytic and MHCII(hi), but are
      resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10
      constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int)
      cells is present in resting colon and it expands during experimental colitis.
      Ly6C(hi)CCR2(+) monocytes can give rise to all mphi subsets in both healthy and
      inflamed colon and we show that the CX3CR1(int) pool represents a continuum in
      which newly arrived, recently divided monocytes develop into resident CX3CR1(hi)
      mphi. This process is arrested during experimental colitis, resulting in the
      accumulation of TLR-responsive pro-inflammatory mphi. Phenotypic analysis of
      human intestinal mphi indicates that analogous processes occur in the normal and
      Crohn's disease ileum. These studies show for the first time that resident and
      inflammatory mphi in the intestine represent alternative differentiation outcomes
      of the same precursor and targeting these events could offer routes for
      therapeutic intervention in IBD.

PMID- 22990623
TI  - Double-stranded RNA induces molecular and inflammatory signatures that are
      directly relevant to COPD.
AB  - Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double
      stranded (ds)RNA, a molecular pattern associated with viral infections, that is
      used to exacerbate inflammation in lung injury models. Despite its frequent use,
      there are no detailed studies of the responses elicited by a single topical
      administration of poly I:C to the lungs of mice. Our data provides the first
      demonstration that the molecular responses in the airways induced by poly I:C
      correlate to those observed in the lungs of chronic obstructive pulmonary disease
      (COPD) patients. These expression data also revealed three distinct phases of
      response to poly I:C, consistent with the changing inflammatory cell infiltrate
      in the airways. Poly I:C induced increased numbers of neutrophils and natural
      killer cells in the airways, which were blocked by CXCR2 and CCR5 antagonists,
      respectively. Using gene set variation analysis on representative clinical data
      sets, gene sets defined by poly I:C-induced differentially expressed genes were
      enriched in the molecular profiles of COPD but not idiopathic pulmonary fibrosis
      patients. Collectively, these data represent a new approach for validating the
      clinical relevance of preclinical animal models and demonstrate that a dual
      CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.

PMID- 22990624
TI  - Human cervicovaginal mucus contains an activity that hinders HIV-1 movement.
AB  - Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1)
      entry during male-to-female transmission. Cervical mucus (CM) is produced by the
      endocervix and forms a layer locally as well as in the vaginal compartment in the
      form of cervicovaginal mucus (CVM). To study the potential barrier function of
      each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and
      CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were
      digitally tracked and mean-squared displacement was calculated. The mobility of
      beads increased significantly in CVM compared with CM, consistent with the known
      decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was
      significantly hindered in the same CVM samples in which bead diffusion was
      unhindered. Inhibition of virus transport was envelope-independent. Our results
      reveal a previously unknown activity in CVM that is capable of impeding HIV-1
      mobility to enhance mucosal barrier function.

PMID- 22990625
TI  - Colonic patch and colonic SILT development are independent and differentially
      regulated events.
AB  - Intestinal lymphoid tissues have to simultaneously ensure protection against
      pathogens and tolerance toward commensals. Despite such vital functions, their
      development in the colon is poorly understood. Here, we show that the two
      distinct lymphoid tissues of the colon-colonic patches and colonic solitary
      intestinal lymphoid tissues (SILTs)-can easily be distinguished based on
      anatomical location, developmental timeframe, and cellular organization.
      Furthermore, whereas colonic patch development depended on CXCL13-mediated
      lymphoid tissue inducer (LTi) cell clustering followed by LTalpha-mediated
      consolidation, early LTi clustering at SILT anlagen did not require CXCL13, CCR6,
      or CXCR3. Subsequent dendritic cell recruitment to and gp38(+)VCAM-1(+) lymphoid
      stromal cell differentiation within SILTs required LTalpha; B-cell recruitment
      and follicular dendritic cell differentiation depended on MyD88-mediated
      signaling, but not the microflora. In conclusion, our data demonstrate that
      different mechanisms, mediated mainly by programmed stimuli, induce the formation
      of distinct colonic lymphoid tissues, therefore suggesting that these tissues may
      have different functions.

PMID- 22990626
TI  - Changes in natural killer cell subpopulations over a winter training season in
      elite swimmers.
AB  - Immune changes and increased susceptibility to infection are often reported in
      elite athletes. Infectious episodes can often impair training and performance
      with consequences for health and sporting success. This study monitored the
      occurrence of episodes of upper respiratory symptoms (URS) and the variation in
      circulating NK cells, CD56(bright) and CD56(dim) NK cells subpopulations, over a
      winter swimming season. Nineteen national elite swimmers and 11 non-athlete
      controls participated in this study. URS episodes were monitored using daily log
      books. Blood samples were taken at rest at four time points during the season:
      before the start of the season (t1--middle September), after 7 weeks of an
      initial period of gradually increasing training load (t2--early November), after
      6 weeks of an intense training cycle (t3--late February) and 48 h after the main
      competition (t4--early April) and from the controls at three similar time points
      (t1--early November; t2--late February; t3--early April). In the swimmers, the
      occurrence of URS clustered around the periods of elevated training load (67 %).
      No URS were reported at equivalent time points in the non-athletes. Athletes
      showed a decrease in the percentage (t2 = 21 %; t3 = 27 %; t4 = 17 %) and
      absolute counts of circulating NK cells (t2 = 35 %; t3 = 22 %; t4 = 22 %),
      coinciding with the periods of increased training load, never recovering to the
      initial values observed at the start of the season. The reduction in the
      CD56(dim) and an increase in the CD56(bright) NK cell subpopulations were
      significant at t2 and t3 (p < 0.05). Concomitant with the fall in values of NK
      cells, in athletes that shown more than three URS episodes, a moderate
      correlation (r = 0.493; p = 0.036) was found between CD56(bright)/CD56(dim) ratio
      and the number of URS episodes after the more demanding training phase (t3). At
      t3, a lower value of CD56 cell counts was found in the group who reported three
      or more URS episodes (t = 2.239; p = 0.032). A progressive significant decrease
      in the expression of CD119, the receptor for IFN-gamma, on the CD56(dim) cells
      was found over the season and an elevation in Granzyme B expression was
      coincident with the more demanding training phases. Periods of highly demanding
      training seem to have a negative impact on innate immunity mediated by NK cell
      subsets, which could partially explain the higher frequency of URS observed
      during these training phases.

PMID- 22990627
TI  - Increase in IL-6, TNF-alpha, and MMP-9, but not sICAM-1, concentrations depends
      on exercise duration.
AB  - It has been suggested that exercise intensity is of importance in the regulation
      of increase in pro-inflammatory molecules, but there is still a debate about the
      effect of duration on these molecules. Therefore, the effect of exercise duration
      on the serum concentrations of interleukin-6 (IL-6), tumour necrosis factor-alpha
      (TNF-alpha), soluble form of intercellular adhesion molecule-1 (sICAM-1), and
      matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18
      marathon (M) male amateur runners who completed their exercise task in 1.8 +/-
      0.2 (mean +/- standard deviation) and 3.6 +/- 0.4 h, respectively (thus, average
      speed was 11.7 +/- 1.5 and 11.9 +/- 1.8 km h(-1), respectively). Blood was
      sampled 2 days before, 15 min after, and 28 h after the race. IL-6, TNF-alpha,
      and MMP-9 always increased immediately after exercise, but the increase was
      larger (P < 0.05) in M versus HM (?IL-6: 31 +/- 24 vs. 5 +/- 4 pg ml(-1); ?TNF
      alpha: 1.7 +/- 1.9 vs. 0.5 +/- 0.8 pg ml(-1); MMP-9: 288 +/- 216 vs. 145 +/- 128
      ng ml(-1), respectively). sICAM-1 also increased with exercise, but similarly in
      M and HM (20 +/- 40 vs. 23 +/- 32 ng ml(-1), respectively). Only sICAM-1 remained
      elevated 28 h post-exercise in both HM and M, while IL-6, TNF-alpha, and MMP-9
      returned to pre-exercise levels. Competitive HM and M races induce significant
      increases in IL-6, TNF-alpha, sICAM-1, and MMP-9 concentrations. As HM and M
      runners performed the competition with similar absolute intensity, the difference
      in response between the groups suggests that exercise duration is of importance
      in the regulation of IL-6, TNF-alpha, and MMP-9, but not sICAM-1 concentrations
      in response to prolonged running.

PMID- 22990628
TI  - Exercise-induced endocannabinoid signaling is modulated by intensity.
AB  - Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are
      densely expressed in brain networks responsible for reward. Recent work shows
      that exercise activates the eCB system in humans and other mammals, suggesting
      eCBs are partly responsible for the reported improvements in mood and affect
      following aerobic exercise in humans. However, exercise-induced psychological
      changes reported by runners are known to be dependent on exercise intensity,
      suggesting that any underlying molecular mechanism should also change with
      varying levels of exercise intensity. Here, we examine circulating levels of eCBs
      following aerobic exercise (treadmill running) in recreationally fit human
      runners at four different intensities. We show that eCB signaling is indeed
      intensity dependent, with significant changes in circulating eCBs observed
      following moderate intensities only (very high and very low intensity exercises
      do not significantly alter circulating eCB levels). Our results are consistent
      with intensity-dependent psychological state changes with exercise and therefore
      support the hypothesis that eCB activity is related to neurobiological effects of
      exercise. Thus, future studies examining the role of exercise-induced eCB
      signaling on neurobiology or physiology must take exercise intensity into
      account.

PMID- 22990629
TI  - Revaluation of collateral pathways as escape routes from hyperemia/hyperperfusion
      following surgical treatment for carotid stenosis.
AB  - BACKGROUND: Although acetazolamide-challenged single-photon emission CT (SPECT)
      is recommended before carotid endarterectomy (CEA) and carotid artery stenting
      (CAS), given the relationship between preoperative decreased cerebrovascular
      reserve (CVR) and postoperative cerebral hyperperfusion syndrome (CHS), it is
      controversial whether all cases should be checked. METHODS: I-IMP-SPECT at rest
      was performed for 65 operative cases of carotid stenoses. At preoperative MR
      angiography we classified cases into two groups: G, featuring an anterior
      communicating artery with bilateral A1 with/without posterior communicating
      arteries; and P, a poor-escape-route group which did not match these criteria.
      Postoperative rCBF patterns were divided into two types: B, bilateral rCBF
      increase; and I, ipsilateral rCBF increase. RESULTS: Cases with high
      postoperative increase rate of rCBF were most frequently found in Group P and the
      Type I cases (p < 0.001). All four cases with hyperemia or hyperperfusion
      belonged to Group P. Only two out of 48 patients in Group G were Type I, both
      demonstrating a preoperative rCBF decrease rate more than 10 % as compared to the
      contralateral side. CONCLUSIONS: From the present study, preliminary analysis of
      escape routes by preoperative MR angiography before surgical treatment of carotid
      stenosis is recommended and CVR investigation with acetazolamide-challenge SPECT
      should be considered for those relatively few cases with poor escape routes.

PMID- 22990630
TI  - Vertebral artery injury in destabilized midcervical spine trauma; predisposing
      factors and proposed mechanism.
AB  - BACKGROUND: By now it has been well established that vertebral artery injury
      (VAI) is associated with unstable cervical spine injuries resulting from blunt
      trauma. A more complete understanding of predisposing factors and the mechanism
      of injury in VAI should result in improved outcomes and reduced risk for patients
      with VAI associated with unstable cervical spine injury following blunt trauma.
      The authors report statistical outcome and hypothesis to more thoroughly examine
      the predisposing factors for VAI, of which management is controversial, in
      destabilized midcervical spine trauma. METHODS: Ninety-one of 131 consecutive
      patients who underwent surgery for a traumatically destabilized subaxial cervical
      spine were included, and results were analyzed statistically by logistic
      regression. RESULTS: Eighteen patients (19.8 % of 91 patients) had a VAI
      associated with midcervical spine trauma (C2-C6). In univariate statistical
      analysis, transverse foramen fracture (P = 0.002), facet dislocation (P = 0.014),
      and facet fracture (P = 0.001) were significant risk factors. However, only facet
      fracture was determined to be significant risk factor after multivariate analysis
      (P = 0.006, odds ratio 20.98). It is hypothesized that a VAI occurs in a
      midcervical spine injury when a facet fracture allows the bony compartment to
      impinge on the relatively narrow free space of the intervertebral foramen, which
      is also occupied by the cervical root. CONCLUSION: A facet fracture is the most
      important risk factor for VAI in patients with a destabilized midcervical spine
      injury. Patients with a C2-C6 facet fracture may require a definitive evaluation
      with vertebral artery imaging.

PMID- 22990631
TI  - Role of gastric lavage in vigorous neonates born with meconium stained amniotic
      fluid.
AB  - OBJECTIVE: To compare reduction in incidence of feed intolerance in neonates born
      with meconium stained amniotic fluid (MSAF) by use of gastric lavage to those who
      did not receive lavage. METHODS: This Randomized controlled trial was conducted
      in all vigorous newborns delivered through MSAF, with birth weight >=1800 g and
      gestation >=34 wk. In the lavage group, gastric lavage with 10 ml/kg of normal
      saline was done. RESULTS: Twelve neonates in the lavage group (n = 124) developed
      feed intolerance compared to 16 neonates in control group (n = 120), (p = .309;
      OR 0.69; 95%CI 0.27-1.58). No difference in any other morbidity was noted.
      CONCLUSIONS: Gastric lavage in neonates with MSAF does not reduce feed
      intolerance, irrespective of thickness of MSAF and it confers no advantages.

PMID- 22990632
TI  - MRI findings in kernicterus.

PMID- 22990633
TI  - Obturator hernia of the fallopian tube.
AB  - Obturator hernia of the fallopian tube is extremely rare. Multidetector computed
      tomography of a 43-year-old nulliparous woman with sudden onset lower right
      abdominal pain showed a low-density mass in the right obturator canal suspected
      of being an obturator hernia of the uterine adnexa. She was diagnosed as having
      an incarcerated obturator hernia of the fallopian tube at operation and treated
      with prosthetic mesh. Obturator hernia of the fallopian tube is very rare, and
      all cases reported in the literature were localized on the right side, perhaps
      due to the lesser mobility of the left than the right fallopian tube.

PMID- 22990634
TI  - An alternative technique for anterior chest wall reconstruction: the sternal
      allograft transplantation.
AB  - OBJECTIVES: Sternal resection is indicated for a variety of pathological
      conditions, mainly neoplastic or related to sternotomy complications. Resection
      of the sternum generally leaves a large chest-wall defect, and reconstruction is
      thus the most difficult part of the operation. Correct stabilization of the
      anterior chest wall is very important to avoid secondary complications and
      respiratory failure. In the last few years, different technical solutions have
      been used to reconstruct the sternum. We describe our technique using a sternal
      allograft to reconstruct the anterior chest wall after partial or complete
      sternal resection. METHODS: Between June 2010 and February 2012, four patients
      underwent sternectomy followed by anterior chest wall reconstruction using
      sternal allograft. The sternal allograft was harvested from a multitissue donor
      following Italian legislation for tissue donation. Three patients had neoplastic
      involvement of the sternum, and one had a complete sternal defect as a
      complication of a cardiac operation. RESULTS: We had no operative mortality.
      Three patients underwent partial sternal transplantation, and one underwent total
      sternal replacement. We had no postoperative respiratory insufficiency,
      infections or mechanical failure of the reconstructions. The respiratory function
      was preserved in all patients. The follow-up period was free from complications
      related to the sternal allograft implantation. CONCLUSIONS: The technique of
      sternal allograft transplantation is simple, reproducible and provides excellent
      functional and cosmetic results. Further studies including a larger number of
      patients are needed to understand the biology of the allograft and the long-term
      results of this technique.

PMID- 22990635
TI  - An unusual cause of pulmonary artery pseudoaneurysm: acrylate embolism.
AB  - Sclerotherapy is commonly used to manage bleeding from oesophageal varices. In a
      patient with cirrhosis of the liver, sclerotherapy with bucrylate was followed by
      a pulmonary embolism and then by a decline in general health. A chest radiograph
      taken 5 months later disclosed a left perihilar opacity, surrounding and invading
      the pulmonary artery. Despite moderate fixation by positron emission tomography
      and inconclusive bronchoscopy findings, an upper left lobectomy was deemed in
      order. A left pulmonary artery pseudoaneurysm was found during the surgery. The
      pseudoaneurysm ruptured during dissection, requiring a left pneumonectomy. The
      pathological examination showed shredding of the left pulmonary artery, which
      contained foreign material. At points of contact with this material, destruction
      and severe polymorphic inflammation of the pulmonary parenchyma were noted. There
      was no evidence of tumour or infection. These findings strongly suggested an
      iatrogenic pulmonary artery pseudoaneurysm related to a bucrylate embolism
      through porto-systemic vascular shunts. We are not aware of previously reported
      cases.

PMID- 22990636
TI  - Male tawny dragons use throat patterns to recognize rivals.
AB  - The ability to distinguish between familiar and unfamiliar conspecifics is
      important for many animals, especially territorial species since it allows them
      to avoid unnecessary interactions with individuals that pose little threat. There
      are very few studies, however, that identify the proximate cues that facilitate
      such recognition in visual systems. Here, we show that in tawny dragons
      (Ctenophorus decresii), males can recognize familiar and unfamiliar conspecific
      males based on morphological features alone, without the aid of chemical or
      behavioural cues. We further show that it is the colour pattern of the throat
      patches (gular) that facilitates this recognition.

PMID- 22990637
TI  - [Hypothalamic dysfunction in obesity].
AB  - Obesity, defined as abnormal or excessive fat accumulation that may impair life
      quality, is one of the major public health problems worldwide. It results from an
      imbalance between food intake and energy expenditure. The control of energy
      balance in animals and humans is performed by the central nervous system (CNS) by
      means of neuroendocrine connections, in which circulating peripheral hormones,
      such as leptin and insulin, provide signals to specialized neurons of the
      hypothalamus reflecting body fat stores, and induce appropriate responses to
      maintain the stability of these stores. The majority of obesity cases are
      associated with central resistance to both leptin and insulin actions. In
      experimental animals, high-fat diets can induce an inflammatory process in the
      hypothalamus, which impairs leptin and insulin intracellular signaling pathways,
      and results in hyperphagia, decreased energy expenditure and, ultimately,
      obesity. Recent evidence obtained from neuroimaging studies and assessment of
      inflammatory markers in the cerebrospinal fluid of obese subjects suggests that
      similar alterations may be also present in humans. In this review, we briefly
      present the mechanisms involved with the loss of homeostatic control of energy
      balance in animal models of obesity, and the current evidence of hypothalamic
      dysfunction in obese humans.

PMID- 22990638
TI  - [Probability of arterial hypertension from anthropometric measures in adults].
AB  - OBJECTIVE: To associate anthropometric measures with arterial hypertension and
      develop a mathematical model to estimate this probability. SUBJECTS AND METHODS:
      A cross-sectional study was carried out with 3,445 adults of both sexes, between
      18 and 60 years of age. Body mass index (BMI), waist-to-height ratio (WHR), waist
      circumference (HC), in addition age and sex were assessed. Blood pressure (BP)
      was measured and classified according to World Health Organization (WHO) and
      Brazilian Society of Hypertension (SBH) recommendations, using frequency
      analyses, correlation and logistic regression between variables, with p < 0.05.
      RESULTS: Males were twice as likely as woman to have hypertension, and for each
      year of life, the chance of hypertension increased 1.04 times. Odds ratio of
      hypertension in overweight individual increased two times, and in obese subjects,
      four times. CONCLUSION: Changes in body composition with advancing age,
      especially in men, were associated with hypertension, and assessment of these
      changes was relevant in the identification of this disease.

PMID- 22990639
TI  - [Level of physical activity in the prevention of excess visceral fat in
      postmenopausal women: how much is needed?].
AB  - OBJECTIVE: To analyze the level of physical activity (kcal/week) needed to
      prevent excess visceral fat in postmenopausal women. SUBJECTS AND METHODS: The
      sample included 239 women with a mean age of 57.2 years. Visceral fat area (VFA)
      was measured by octopolar bioelectrical impedance, and physical activity, by the
      long version IPAQ. ROC Curves (Receiver Operating Characteristic) were drawn, and
      a 95% confidence interval was used. RESULTS: The areas under the ROC curve for
      moderate physical activity and walk proved to be significant. Weekly expenditure
      of 1,601 kcal in walking, or 2,283 kcal in moderate physical activity were
      identified as good cutoff values to prevent excess VFA. CONCLUSION: Mild to
      moderate physical activity, with a caloric expenditure between 1,601 and 2,283
      kcal/week, prevents excess central adiposity in postmenopausal women.

PMID- 22990640
TI  - [Evaluation of body weight in patients with Graves' disease during the treatment
      with methimazole].
AB  - OBJECTIVE: To evaluate weight change during hyperthyroidism treatment, and to
      correlate it with IL-6 and TNF-alpha concentrations. SUBJECTS AND METHODS: Forty
      two patients were included. Body weight (BW), body mass index (BMI), clinical and
      laboratory characteristics were recorded. IL-6 and TNF-alpha were determined
      before treatment with methimazole (MMI) and in euthyroidism. RESULTS: BW was
      59.62 +/- 11.5 kg in hyperthyroidism, and 69.91 +/- 14.4 kg in euthyroidism (p <
      0.001). BMI increased from 23.1 +/- 3.8 kg/m(2) to 27 kg/m(2) +/- 4.7 during
      treatment (p < 0.0001). Before treatment, 66.6% subjects had BMI < 25 kg/m(2) and
      33.3%, BMI > 25 kg/m(2). In euthyroidism, 38% of patients had BMI < 25 kg/m(2)
      and 62%, BMI > 25 kg/m(2) (p = 0.01). In euthyroidism, we found a significant
      reduction in IL-6 and TNF-alpha concentrations, but no correlation between IL-6
      and TNF-alpha, and BW or BMI. CONCLUSION: An important increase in BW and BMI was
      observed during hyperthyroidism treatment, and IL-6 and TNF-alpha alterations
      were only related with return to euthyroidism.

PMID- 22990641
TI  - [Quantitative ultrasound of the calcaneus, bone densitometry and vertebral
      morphometry in men over the age of 60 years].
AB  - OBJECTIVES: To compare calcaneal ultrasonometry and bone densitometry in the
      evaluation of morphometric vertebral fractures in men over 60 years of age.
      SUBJECTS AND METHODS: We studied 96 men over 60 years of age by means of bone
      densitometry of the spine, femur and radius, lateral radiograph of the thoracic
      and lumbar spine, and calcaneal ultrasonometry. RESULTS: Fifty-one percent of men
      had osteoporosis and vertebral fractures. Correlation was found between
      ultrasonometry stiffness index, T-score and bone mineral density of the spine,
      femur and radius (p < 0.01). Regarding the presence of fractures, there was a
      correlation only with BMD of the ultradistal radius (UD) and radius 33%. ROC
      curve showed accuracy only of UD radius BMD in detecting vertebral fractures.
      CONCLUSIONS: Our study showed a correlation between osteoporosis diagnosis by
      ultrasonometry and densitometry in men over 60 years. It also showed a
      correlation between morphometric vertebral fracture and bone mineral density of
      the forearm.

PMID- 22990642
TI  - [Changes in bone metabolism markers in women after Roux-en-Y gastric bypass].
AB  - OBJECTIVE: To evaluate bone turnover markers and bone mineral density (BMD) in
      women after Roux-en-Y (RYGB) gastric bypass. SUBJECTS AND METHODS: In a cross
      sectional study, 48 women post-RYGB after three years, and 41 healthy women were
      evaluated. EVALUATIONS: body mass index (BMI); physical activity; food intake;
      serum levels of calcium, phosphorus, magnesium, alkaline phosphatase, C-terminal
      telopeptide (CTX), intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD),
      osteocalcin, urinary calcium and BMD. RESULTS: Significantly higher levels were
      observed for osteocalcin (p < 0.001), CTX (p < 0.001), and PTH (p < 0.001) in the
      RYGB group when compared with the control group; 25OHD deficiency/insufficiency
      was more frequent in the RYGB group (p = 0.010), even after adjusted for
      nutritional status, and it was associated with secondary hyperparathyroidism (p =
      0.025); there was no difference in BMD between the groups. Energy (p = 0.036) and
      protein intake (p = 0.004) were lower in the RYGB group. CONCLUSION: Patients
      submitted to RYGB showed a significantly higher frequency of vitamin D
      deficiency, secondary hyperparathyroidism, and increase in bone remodeling
      markers, with no difference in BMD status.

PMID- 22990643
TI  - [Massive pericardial effusion as initial manifestation of hypothyroidism].
AB  - The aim of this study is to report a rare case of massive pericardial effusion as
      initial manifestation of hypothyroidism. A previously healthy 21-year-old female
      patient suddenly began presenting dyspnea at rest and lower limb edema. Routine
      laboratory tests performed at admission showed hypothyroidism (TSH 146.14 mUI/L)
      and echocardiography showed significant pericardial effusion. Therapy was
      instituted with levothyroxine, resulting in clinical improvement without
      pericardiocentesis. The patient was followed up for 1 year, with total remission
      of dyspnea and edema. However, she developed typical symptoms of hypothyroidism,
      and remained with asthenia, dyslipidemia, weight gain, and mild pericardial
      effusion at the end of one year, even with the optimization of the levothyroxine
      dose. This case highlights the need for early investigation of hypothyroidism in
      patients with pericardial effusion.

PMID- 22990644
TI  - [Acute suppurative thyroiditis with multiple complications].
AB  - Acute suppurative thyroiditis is a rare disorder, most often caused by
      Staphylococcus aureus or Streptococcus pneumoniae, which affects particularly
      children with pyriform sinus fistula. In adults, the main pathogenic mechanism
      seems to be hematogenous dissemination from a focus of infection in the
      oropharynx or respiratory tract. The initial signs and symptoms of acute
      thyroiditis are similar to those of acute pharyngitis and subacute thyroiditis.
      This fact often delays diagnosis and increases the risk of complications. We
      report the case of a previously healthy, 28-year-old man who, after being
      affected by tonsillitis, developed suppurative thyroiditis complicated by
      thyrotoxicosis; a large abscess in the right lobe of the thyroid extending to the
      thorax introitus, which caused a trachea deviation and compressed large vessels;
      associated with internal jugular vein thrombosis, and sepsis.

PMID- 22990645
TI  - Persistent primary hyperparathyroidism: an uncommon location for an ectopic gland
      -case report and review.
AB  - Primary hyperparathyroidism (PHPT) is a common endocrine disorder that mainly
      affects middle-aged women. Patients are usually asymptomatic. The disease might
      be ascribable to hyperplasia, carcinoma, and single or multiple adenomas. PHPT
      may be sporadic or familial, the latter comprising multiple endocrine neoplasia
      type 1 or 2A, familial benign hypocalciuria hypercalcemia, and
      hyperparathyroidism-jaw tumor syndrome. The most common causes for persistent
      PHPT are multiglandular disease, and missed abnormal ectopic or orthotopic
      parathyroid glands. Imaging localization studies should precede a new surgical
      intervention. Ectopic parathyroid glands are rarely located at the aortopulmonary
      window. For diagnosis confirmation, (99m)Tc-sestamibi SPECT/CT seems to be an
      advantageous test. Another possibility is to perform (99m)Tc-sestamibi followed
      by thoracic CT or MRI. Parathyroidectomy may be performed by means of median
      sternotomy, thoracotomy, or video-assisted thoracoscopy. We describe a case of
      persistent primary hyperparathyroidism due to the presence of an ectopic
      parathyroid gland found at the aortopulmonary window. As the investigation
      necessary to clarify the etiology of recurrent nephrolithiasis proceeded, the
      diagnosis of PHPT was determined. The patient underwent subtotal
      parathyroidectomy; nevertheless, PHPT persisted. Genetic syndromes that could
      account for this condition were excluded. Imaging studies available at that time
      were not able to locate abnormal glands; moreover, the patient refused to undergo
      surgical exploration. Later, the patient underwent (99m)Tc-sestamibi SPECT/CT,
      which revealed a parathyroid gland at the aortopulmonary window.

PMID- 22990646
TI  - [Fates at the psychiatric hospital of Klagenfurt during National Socialism].
AB  - In this article the fate of Mr. B. is described as an example for the fate of
      hundreds of mentally ill patients of the "Landes-Irrenanstalt of Klagenfurt",
      murdered during the era of National Socialism. This extraordinary fate marks two
      outstanding aspects of history of medicine, the treatment of syphilis with
      malaria and the organised mass murder of mentally ill people during the cynic era
      of National Socialism. Beyond this historical perspective reconstructive
      biographical work together with relatives is presented as a proactive duty of
      psychiatric institutions. 

PMID- 22990647
TI  - Utilization of mastectomy and reconstruction in the outpatient setting.
AB  - BACKGROUND: Reconstruction rates after mastectomy have been reported to range
      from 25-40%; however, most studies have focused on patients treated in an
      inpatient setting. We sought to determine the utilization of outpatient
      mastectomy and use of breast reconstruction in Southern California. METHODS:
      Postmastectomy reconstruction rates were determined from the California Office of
      Statewide Health Planning and Development database from 2006-2009 using CPT codes
      and similarly from an inpatient database using ICD-9 codes. Reconstruction rates
      were compared between the inpatient and outpatient setting. For the outpatient
      setting, univariate and multivariate odds ratios with 95% confidence intervals
      were estimated for relative odds of immediate reconstruction versus mastectomy
      alone. RESULTS: The percentage of patients undergoing outpatient mastectomy
      ranged from 20.4 to 23.9% of the total number of all patients undergoing
      mastectomy. Whereas immediate inpatient reconstruction increased from 29.2 to
      41.6% (overall rate 35.5%), the proportion of outpatients undergoing
      reconstruction only increased from 7.7 to 10.3% (overall rate 9.1%). Similar to
      the inpatient setting, in multivariate analysis, age, insurance status,
      race/ethnicity, and type of hospital were significantly associated with the use
      of reconstruction in the outpatient setting. CONCLUSIONS: A substantial number of
      patients undergo outpatient mastectomy with low rates of reconstruction. Although
      the choice of an outpatient mastectomy may certainly represent a selection bias
      for those not choosing reconstruction, an increase in the use of outpatient
      mastectomy may result in decreases in the use of postmastectomy reconstruction.

PMID- 22990648
TI  - Management of bowel obstruction in patients with stage IV cancer: predictors of
      outcome after surgery.
AB  - BACKGROUND: Patients with stage IV cancer and bowel obstruction (BO) present a
      complicated management problem. We sought to determine if specific parameters
      could predict outcome after surgery. METHODS: Records of patients with stage IV
      cancer and BO treated from 1991 to 2008 were reviewed. For surgical patients, 30
      day morbidity and 90-day mortality were assessed using exact multivariable
      logistic regression methods. RESULTS: Of 198 patients, 132 (66.7%) underwent
      surgery, 66 medical treatment alone, and demographics were similar. A total of 41
      patients (20.7%) were diagnosed with stage IV cancer and BO synchronously, all
      treated surgically; the remaining presented metachronously. Medically managed
      patients were more likely to have received chemotherapy in the 30 days prior to
      BO (45 of 66 [68.2%] vs 40 of 132 [30.3%], p < .01). In the surgical group, 30
      day morbidity was 35.6%, while 90-day mortality was 42.3%. Median overall
      survival for synchronous patients was 14.1 months (95% confidence interval [95%
      CI] 7.6-23.2), and 3.7 months (95% CI 2.5-5.2) and 3.6 months (95% CI 1.5-5.2)
      for metachronous patients treated surgically and medically, respectively. A
      multivariate model for 90-day surgical mortality identified low serum albumin,
      metachronous presentation, and ECOG > 1 as predictors of death (p < .05). A model
      for 30-day surgical morbidity yielded low hematocrit as a predictive factor (p <
      .05). CONCLUSIONS: This cohort identifies characteristics indicative of morbidity
      and mortality in stage IV cancer and BO. Low serum albumin, ECOG > 1, and
      metachronous presentation predicted for 90-day surgical mortality. These data
      suggest factors that can be used to frame treatment discussion plans with
      patients.

PMID- 22990649
TI  - Concerted proton migration along short hydrogen bonded water bridges in
      bipyridine-water clusters.
AB  - The outcome of reactions between D(2)O and size-selected ionic clusters of the
      type MH(+)(H(2)O)(n) (M = bipyridine, n = 1-30) shows that H-D-exchange is
      significantly higher for 2,2'-bipyridines than for 4,4'-bipyridines. This gives
      strong support for the idea that the existence of short water wires between the
      two nitrogen sites is essential to proton migration in water clusters containing
      basic sites.

PMID- 22990650
TI  - Individuality in FGF1 expression significantly influences platinum resistance and
      progression-free survival in ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is frequently advanced at presentation when treatment
      is rarely curative. Response to first-line platinum-based chemotherapy
      significantly influences survival, but clinical response is unpredictable and is
      frequently limited by the development of drug-resistant disease. METHODS: We used
      qRT-PCR analysis to assess intertumour differences in the expression of
      fibroblast growth factor 1 (FGF1) and additional candidate genes in human ovarian
      tumours (n=187), and correlated individuality in gene expression with tumour
      histology, chemotherapy response and survival. We used MTT assays to assess
      platinum chemosensitivity in drug-sensitive and drug-resistant ovarian cell
      lines. RESULTS: Marked intertumour differences in gene expression were observed,
      with each tumour having a unique gene expression profile. Nine genes, including
      FGF1 (P=1.7 * 10(-5)) and FGFR2 (P=0.003), were differentially expressed in
      serous and nonserous tumours. MDM2 (P=0.032) and ERBB2 (P=0.064) expression was
      increased in platinum-sensitive patients, and FGF1 (adjusted log-rank test
      P=0.006), FGFR2 (P=0.04) and PDRFRB expression (P=0.037) significantly inversely
      influenced progression-free survival. Stable FGF1 gene knockdown in platinum
      resistant A2780DPP cells re-sensitised cells to both cisplatin and carboplatin.
      CONCLUSION: We show for the first time that FGF1 is differentially expressed in
      high-grade serous ovarian tumours, and that individuality in FGF1 expression
      significantly influences progression-free survival and response to platinum-based
      chemotherapy.

PMID- 22990651
TI  - Influence of vitamin D binding protein on the association between circulating
      vitamin D and risk of bladder cancer.
AB  - BACKGROUND: There is little research investigating the role of vitamin D binding
      protein (DBP) in the association between 25-hydroxyvitamin D (25(OH)D) and
      disease risk. METHODS: Within the Alpha-Tocopherol, Beta-Carotene Cancer
      Prevention (ATBC) Study, 250 bladder cancer cases were randomly sampled and
      matched 1:1 to controls on age and date of blood collection. Odds ratios (OR) and
      95% confidence intervals (CI) of bladder cancer were estimated by quartiles of
      DBP (measured by ELISA), 25(OH)D and the molar ratio of 25(OH)D:DBP, a proxy for
      free circulating 25(OH)D. Analyses were also conducted stratifying 25(OH)D by DBP
      (median split) and vice versa. RESULTS: We found no direct association between
      circulating DBP levels and bladder cancer risk (P-trend=0.83). The inverse
      association between 25(OH)D and bladder cancer risk was unchanged after
      adjustment for DBP (Q4 vs Q1 OR=0.61, 95% CI=0.36-1.05; P-trend=0.04), and was
      stronger among men with lower DBP (low DBP: 25(OH)D Q4 vs Q1 OR=0.47, 95% CI=0.23
      1.00; high DBP: 25(OH)D Q4 vs Q1 OR=0.83, 95% CI=0.40-1.75; P for
      interaction=0.11). CONCLUSION: Our findings provide additional support for an
      aetiologic role for vitamin D in bladder cancer and suggest that free, rather
      than total, circulating vitamin D may be a more relevant exposure when examining
      bladder and, perhaps, other cancers.

PMID- 22990652
TI  - Phase I trial of axitinib combined with platinum doublets in patients with
      advanced non-small cell lung cancer and other solid tumours.
AB  - BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and
      pharmacokinetics of axitinib, a potent and selective second-generation inhibitor
      of vascular endothelial growth factor receptors, combined with platinum doublets
      in patients with advanced non-small cell lung cancer (NSCLC) and other solid
      tumours. METHODS: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.)
      with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following
      determination of the maximum tolerated dose, a squamous cell NSCLC expansion
      cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin.
      RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia
      (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the
      gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse
      events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade
      >=3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The
      objective response rate was 37.0% for patients receiving
      axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving
      axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and
      chemotherapeutic agents were similar when administered alone or in combination.
      CONCLUSION: Axitinib 5 mg b.i.d. may be combined with standard
      paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of
      overt drug-drug interactions. Both combinations demonstrated clinical efficacy
      and were well tolerated.

PMID- 22990654
TI  - Second to fourth digit ratio (2D:4D), breast cancer risk factors, and breast
      cancer risk: a prospective cohort study.
AB  - BACKGROUND: We aimed to assess whether 2D:4D measures are associated with breast
      cancer risk. METHODS: We derived the ratio of the lengths of the index and ring
      fingers (2D:4D), and right minus left 2D:4D (Delta(r-l)) from digit lengths
      measured from photocopies of participants' hands collected during a recent follow
      up of the Melbourne Collaborative Cohort Study, a prospective study including 24
      469 women. Of the 9044 women with available data, we identified 573 incident
      breast cancer cases. Hazard ratios (HR) and 95% confidence intervals (CI) for a
      one standard deviation difference in 2D:4D measures were obtained from Weibull
      survival models, and linear regression models were used to examine potential
      associations between 2D:4D measures and age at menarche and menopause. RESULTS:
      We found a direct association between left 2D:4D and breast cancer risk, an
      inverse association between Delta(r-l) and risk of breast cancer, but no
      association between right 2D:4D and breast cancer risk. Among breast cancer
      cases, both right 2D:4D and Delta(r-l) were inversely associated with age at
      diagnosis. We also observed associations between both right 2D:4D and Delta(r-l)
      and age at menopause, with increasing digit ratio measures related to earlier
      mean age at menopause. CONCLUSION: Digit ratio measures might be associated with
      breast cancer risk and age at onset of breast cancer. If confirmed in other
      studies, this suggests that lower exposure or sensitivity to prenatal
      testosterone might be associated with lower risk of breast cancer.

PMID- 22990655
TI  - Preoperative screening and perioperative care of the patient with sleep
      disordered breathing.
AB  - PURPOSE OF REVIEW: Emerging data are raising concerns that patients with known or
      suspected obstructive sleep apnea (OSA) are at increased risk for a myriad of
      perioperative complications. Strategies to identify patients preoperatively with
      OSA, or at risk for OSA, are being advocated. In addition, approaches to identify
      patients most at risk for OSA-related postoperative complications have been
      described. While lacking solid evidence, a number of perioperative management
      strategies have been proposed for the care of these patients. RECENT FINDINGS:
      Recent studies utilizing different methodologies have provided additional
      evidence regarding the impact that OSA can have on postoperative outcomes,
      including increased risk of difficult intubations, adverse pulmonary outcomes,
      and delirium. Tools, such as the STOP-Bang questionnaire and limited channel
      monitoring, have been investigated with regards to their utility to identify not
      only patients at risk for OSA but also those at risk for more severe OSA.
      Consensus-based guidelines for the perioperative care of OSA patients have
      recently been published. SUMMARY: OSA is quite common in patients presenting for
      elective surgery and has been linked to increased perioperative complications.
      Attempts to identify these patients preoperatively appear prudent. Protocols on
      how best to manage these patients are available, although validation of their
      effectiveness is needed.

PMID- 22990653
TI  - Predicting 5-fluorouracil toxicity in colorectal cancer patients from peripheral
      blood cell telomere length: a multivariate analysis.
AB  - BACKGROUND: Identifying various pretreatment factors that predict chemotherapy
      induced toxicity in colorectal cancer (CRC) patients undergoing treatment for
      their disease is crucial to optimising patient care. METHODS: Seventy-three
      patients received adjuvant 5-fluorouracil (5FU)/leucovorin using either the Mayo
      Clinic (n=42) or a weekly schedule (n=31) and evaluated for clinical toxicity.
      Pretreatment blood analysis included measures of plasma uracil and dihydrouracil,
      peripheral blood mononuclear cell (PBMNC) telomere length (TL), standard
      biochemistry and cell differential analysis. On the first day of treatment 5FU
      pharmacokinetic variables of area under the curve, half life and clearance were
      also measured. These variables together with age and gender were used in
      univariate and multivariate analysis as predictors of clinical toxicity. RESULTS:
      For the Mayo schedule the primary toxicities were neutropenia (69%), mucositis
      (58%) and leukopenia (46%), with 70% of patients presenting with haematological
      toxicity >=grade 1 (neutropenia and/or leukopenia). Multivariate analysis showed
      that haematological toxicity was predicted by short TL, high platelet lymphocyte
      ratio (PLR) and low neutrophil count (R(2)=0.38, P<0.0006), whereas mucositis was
      predicted by age, TL and PLR (R(2)=0.34, P<0.001). For the weekly schedule
      diarrhoea predominated (16%), with female gender as the only predictive factor.
      Although measures of uracil metabolism correlated well with 5FU metabolism
      (r=0.45-0.49), they did not indicate abnormal pyrimidine metabolism in this
      cohort and not surprisingly failed to predict for 5FU toxicity. CONCLUSION: Short
      TL of PBMNC and an increased PLR were strong predictors of mucositis and
      haematological toxicity in CRC patients undergoing 5FU treatment in the adjuvant
      setting.

PMID- 22990656
TI  - Roles of gender, age, race/ethnicity, and residential socioeconomics in
      obstructive sleep apnea syndromes.
AB  - PURPOSE OF REVIEW: Review recent research on the roles of gender, race/ethnicity,
      residential socioeconomics and age in obstructive sleep apnea syndromes (OSA) and
      their treatment. RECENT FINDINGS: Men have a higher prevalence of OSA than women
      and require higher continuous positive airway pressure (CPAP) pressures for
      treatment, given similar severity of OSA. When comparing age, women have less
      severe apnea at all ages. Menopause, pregnancy and polycystic ovarian syndrome
      increase the risk for OSA in women. Neck fat and BMI influence apnea-hypopnea
      index (AHI) severity in women; abdominal fat and neck-to-waist ratio do so in
      men. Obesity, craniofacial structure, lower socioeconomic status and neighborhood
      disadvantage may better explain ethnic/racial differences in the prevalence and
      severity of OSA. Ethnicity was no longer significantly associated with OSA
      severity when WHO criteria for obesity were used. SUMMARY: OSA has a male
      predominance; women have a lower AHI than men during certain stages of sleep;
      women require less CPAP pressure for treatment of similar severity of OSA, and
      there are ethnic/racial differences in the prevalence and severity of OSA but
      these may be due to environmental factors, such as living in disadvantaged
      neighborhoods.

PMID- 22990657
TI  - Cognitive dysfunction and obstructive sleep apnea:  from cradle to tomb.
AB  - PURPOSE OF REVIEW: To understand clinical characteristics and risk factors for
      cognitive impairment in patients with obstructive sleep apnea (OSA) syndromes.
      RECENT FINDINGS: Primary snoring increases the risk of neurocognitive impairment
      and lower intelligence quotients in infants and children. Middle-aged adults with
      severe OSA are at greater risk for cognitive impairment than young adults with
      apnea of equal severity. Older women with OSA are at increased risk for minimal
      cognitive impairment or dementia, 5 years later. SUMMARY: Certain age groups
      (younger and older) are particularly susceptible to the negative effects of OSA
      on cognition. Other influences that increase the risk for cognitive dysfunction
      in OSA include premature birth, apolipoprotein e4 allele status and other genetic
      polymorphisms, lower socioeconomic status, fewer years of education, and
      ethnicity.

PMID- 22990658
TI  - The pathophysiology of insomnia:  from models to molecules (and back).
AB  - PURPOSE OF REVIEW: To provide an overview of foundational theories on the
      psychosocial and neurobiological mechanisms that underlie the pathophysiology of
      insomnia, a review of recent findings from across the spectrum of sleep sciences
      that are germane to conceptualizations of insomnia, and how such findings
      contribute to newer integrative models. RECENT FINDINGS: Recent findings come
      from a broad diversity of the sleep research spectrum including basic animal
      science, sleep neuroscience, especially sleep-wake regulation,
      psychoneuroimmunology, human genetics, epidemiology, psychology, and from the
      clinical research realm. SUMMARY: Our review focuses on the factors contributing
      to insomnia and to its maintenance over time as well as the theoretical models
      developed (and developing) to explain this pathophysiology. Early theoretical
      contributions have provided a backbone for insomnia research; the sleep sciences,
      in turn, have supported novel and increasingly complex theoretical models of
      insomnia. The overarching contention is that integrative models are needed that
      are fully comprehensive in scope.

PMID- 22990659
TI  - Stenotrophomonas maltophilia:  to be or not to be a cystic fibrosis pathogen.
AB  - PURPOSE OF REVIEW: Stenotrophomonas maltophilia can cause persistent airway
      colonization and chronic infection in cystic fibrosis (CF) patients. The clinical
      effect of chronic S. maltophilia infection is still a matter of debate. The
      purpose of the review is to summarize studies published during the last 1.5 years
      with a focus on whether S. maltophilia should be regarded as a 'true' CF
      pathogen. RECENT FINDINGS: Studies concerning the microbiological characteristics
      of this microorganism with special focus on identification, virulence factors,
      cross-infection and resistance pattern, and studies on clinical effects of
      chronic infection, specifically serological responses to this infection, negative
      effects on the clinical status and possible effects of antibiotic treatment have
      been reviewed. SUMMARY: S. maltophilia can be identified with certainty, has well
      described virulence factors, is capable of cross-infection and often shows
      multiresistance. Although CF patients with chronic S. maltophilia infection have
      lower lung function parameters compared with other CF patients and experience
      more exacerbations, chronic S. maltophilia infection in itself was not associated
      with a worse clinical outcome. True, pathogenic effects of S. maltophilia could
      not be found, but the presence of chronic S. maltophilia could be a marker of
      more pronounced lung disease in affected patients.

PMID- 22990660
TI  - Dornase alfa (Pulmozyme).
AB  - PURPOSE OF REVIEW: Dornase alfa (Pulmozyme) is one of the most commonly used
      medications to treat the lung disease of cystic fibrosis (CF). As other
      respiratory medications have entered the clinical market, understanding the
      proper use and indication for dornase alfa is increasingly important. In
      addition, dornase alfa is being used to treat other medical conditions. This
      review covers recent publications and expanding indications. RECENT FINDINGS:
      Understanding dornase alfa's mechanism of action and impact on the
      pathophysiology of CF leads to an improved understanding of optimal therapy, ways
      to improve adherence and use with other medications. Most importantly, routine
      use of dornase alfa is associated with improved lung function and survival in
      patients with CF. Outside of CF, potential uses include treating patients with
      empyema or on mechanical ventilation. SUMMARY: Dornase alfa has been available
      for clinical use for nearly 20 years and is one of the most commonly used
      medications in patients with CF. Routine use is associated with a reduced rate of
      pulmonary deterioration and improved survival. Recent clinical reports suggest
      that dornase alfa may have clinical value with other medical problems such as
      complicated pneumonia and mechanically ventilated patients with atelectasis.

PMID- 22990661
TI  - Effects of a Pseudomonas aeruginosa eradication policy in a cystic fibrosis
      clinic.
AB  - PURPOSE OF REVIEW: This review is based upon the recent literature regarding
      eradication of newly acquired infection with Pseudomonas aeruginosa (Psa) in
      patients with cystic fibrosis (CF) and the economic and other effects of such an
      early eradication policy in a CF clinic. RECENT FINDINGS: Various Psa eradication
      protocols which utilize intravenous or aerosol anti-pseudomonal antibiotics, with
      or without oral antibiotics, have been reported. The recent ELITE trial reported
      successful eradication of 90% of Psa in selected Psa antibody negative patients
      after 28 days of tobramycin for inhalation. Another recent report of a protocol
      based on intravenous antibiotic use reported elimination of 'first growth' Psa in
      over 96% of all patients, accompanied by decreased chronic Psa infection,
      decreased anti-Psa treatment costs and decreased hospitalization costs. SUMMARY:
      The effects of early eradication protocols for Psa have included decreased
      prevalence of chronic Psa infection, improved patient health and pulmonary
      function, and decreased hospital and antibiotic costs.

PMID- 22990662
TI  - Can sleep deprivation studies explain why human adults sleep?
AB  - PURPOSE OF REVIEW: This review will concentrate on the consequences of sleep
      deprivation in adult humans. These findings form a paradigm that serves to
      demonstrate many of the critical functions of the sleep states. RECENT FINDINGS:
      The drive to obtain food, water, and sleep constitutes important vegetative
      appetites throughout the animal kingdom. Unlike nutrition and hydration, the
      reasons for sleep have largely remained speculative. When adult humans are
      nonspecifically sleep-deprived, systemic effects may include defects in
      cognition, vigilance, emotional stability, risk-taking, and, possibly, moral
      reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue.
      Procedural, declarative, and emotional memory are affected. Widespread
      alterations of immune function and inflammatory regulators can be observed, and
      functional MRI reveals profound changes in regional cerebral activity related to
      attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on
      the contrary, appears to be more activating and to have lesser effects on
      immunity and inflammation. SUMMARY: The findings support a critical need for
      sleep due to the widespread effects on the adult human that result from
      nonselective sleep deprivation. The effects of selective REM deprivation appear
      to be different and possibly less profound, and the functions of this sleep state
      remain enigmatic.

PMID- 22990663
TI  - Molecular dynamics and free energy studies on Aurora kinase A and its mutant
      bound with MLN8054: insight into molecular mechanism of subtype selectivity.
AB  - Because of the high conservation of ATP-binding sites in kinases, the quest for
      selective kinase inhibitors has been increasingly urgent in recent years. The
      Aurora kinase family represents attractive targets in cancer therapy and several
      small molecule inhibitors targeting Aurora kinases are undergoing clinical
      trials. Among them, MLN8054 has been proved to be a selective Aurora-A inhibitor,
      and is currently being evaluated in a phase I trial for patients with advanced
      solid tumors. But the detailed selectivity mechanism of MLN8054 towards Aurora-A
      over Aurora-B is still not resolved. In the present work, this selectivity
      mechanism was investigated using molecular dynamics simulations and binding free
      energy calculations. The predicted binding conformations and binding affinities
      of MLN8054 to Aurora-A and its mutant that mimics Aurora-B suggest that there
      exists stronger interaction between MLN8054 and Aurora-A through an induced DFG
      up conformation. Further analyses can provide some information about the
      structural basis for the selectivity mechanism. Binding of MLN8054 to Aurora-A
      induces the conformation of the activation loop to adopt an unusual DFG-up
      conformation and opens the hydrophobic pocket of the active site, thus increasing
      the interaction between MLN8054 and the residue Val279. The residue Glu177 in
      Aurora-B displays electrostatic repulsion with MLN8054, while the corresponding
      Thr217 in Aurora-A has favorable interactions with MLN8054. The conformation
      change and the difference between the binding pockets for Aurora-A and B are key
      factors responsible for the selectivity. The results could be helpful for the
      rational design of selective inhibitors of Aurora-A kinase.

PMID- 22990664
TI  - Photoorganocatalysis. What for?
AB  - In the reactions reviewed, an organic molecule under irradiation catalyzes a
      chemical reaction. The activation is based either on hydrogen or on electron
      transfer. Commonly used photoorganocatalysts are aromatic ketones, quinones,
      heterocycles, dyes; intermediates formed are radicals, radical ions and ions from
      precursors such as alkanes, alkenes, amines, ethers etc. Oxidation (mainly
      oxygenation) and reduction processes are obtained along with the alpha
      functionalization of amines and ketones, conjugate additions, cycloadditions etc.
      The key characteristic of the method is the smooth generation of highly reactive
      intermediates under mild conditions.

PMID- 22990665
TI  - Multicohort model for prevalence estimation of advanced malignant melanoma in the
      USA:  an increasing public health concern.
AB  - The aim of the study was to estimate the current prevalence of advanced cutaneous
      malignant melanoma in 2010 in the USA and to project prevalence estimates to the
      year 2015. An excel-based, multicohort natural disease history model was
      developed. It used incidence, recurrence, all-cause mortality, and US population
      data from the up-to-date surveillance, epidemiology, and end results program, the
      US census, and the literature. The prevalence was stratified by tumor stage, sex,
      and age. The model estimated that there were 800 735 malignant melanoma cases
      (258 per 100 000 individuals) in the USA in 2010, of which 10.4% were in advanced
      stages including stage III (22 per 100 000 individuals) and stage IV (four per
      100 000 individuals). Among these advanced cases, 58.8% were men. In total, 42.1%
      of patients with advanced malignant melanoma were 65 years of age and older. Of
      these elderly patients with an advanced stage of the disease, 65.7% were men. The
      total number of cases and number of advanced cases were projected to increase
      from 2010 to 2015 by 24.4 and 21.0%, respectively. There will be approximately
      one million malignant melanoma cases (306 per 100 000 individuals) in the USA in
      2015. The prevalence of advanced malignant melanoma is expected to increase in
      the next few years. Advanced malignant melanoma disproportionately affects men
      and the elderly in the USA.

PMID- 22990666
TI  - CCR7+ central and CCR7- effector memory CD4+ T cells in human cutaneous
      leishmaniasis.
AB  - PURPOSE: The profile of central (=T(CM)) and effector (=T(EM)) memory CD4(+) T
      cell subsets and the possible role as surrogate markers of protection is studied
      in the volunteers with history of cutaneous leishmaniasis (HCL). METHODS: Profile
      of T cell subsets based on CCR7/CD45RA expressions and phenotypic changes after
      soluble Leishmania antigen (SLA) stimulation were analyzed. Then, sorted
      CD4(+)CD45RO(-)CD45RA(+) naive T, CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM,)
      CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) subsets were cultured with SLA for
      proliferation, cytokine production and intracellular cytokine assays. RESULTS: In
      the HCL and control volunteers, the mean frequencies of CD4(+)CD45RA(+)CCR7(+)
      naive T cells and CD4(+)CD45RA(-)CCR7(-) T(EM) cells were higher than the other
      subsets before culture. Frequency of naive T cells and CD4(+)CD45RA(-)CCR7(+)
      T(CM) cells was significantly decreased (P=0.01 for naive T and P<0.05 for T(CM)
      cells) and frequency of T(EM) cells was significantly increased after SLA
      stimulation compared to before culture (P<0.001). By CFSE labeling,
      CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) cells showed more proliferation potential
      than CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM) cells. Stimulation of the T(EM) cells
      in HCL volunteers induced a significantly higher IFN-gamma production (P=0.04)
      with higher number of intracellular IFN-gamma positive cells (P=0.032) than the
      same cells from controls. A significantly higher number of T(CM) cells produced
      IL-2 in HCL volunteers compared with controls (P<0.05). Most of the intracellular
      IFN-gamma positive T(EM) cells were proliferating CFSE-dim populations (P<0.05).
      CONCLUSIONS: A combination of Leishmania-reactive IFN-gamma producing
      CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM) and Leishmania-reactive IL-2 producing
      CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) are identified in individuals with history
      of CL which might play a role in protective recall immune response against
      Leishmania infection.

PMID- 22990667
TI  - Therapeutics to promote CNS repair: a natural human neuron-binding IgM regulates
      membrane-raft dynamics and improves motility in a mouse model of multiple
      sclerosis.
AB  - We have discovered a role for natural autoantibodies in central nervous system
      repair, remyelination and axon protection. These natural human antibodies are of
      the immunoglobulin M (IgM) isotype, and they bind to the surface of neural cells.
      The epitope of the antibody includes sialic acid because treatment with sialidase
      disrupts the binding. A fully human recombinant form of one of these IgMs,
      rHIgM12, has the same properties as the serum-derived IgM. rHIgM12 enhanced
      polarized axonal outgrowth from primary neurons when presented as a substrate in
      vitro and improved motor functions in chronically Theiler's virus-infected SJL
      mice, a model of MS. rHIgM12 bound to neuronal surfaces and induced cholesterol
      and ganglioside (GM1) clustering, indicating that rHIgM12 functions through a
      mechanism of axonal membrane stabilization. Our work demonstrates that a natural
      human neuron-binding IgM can regulate membrane domain dynamics. This antibody has
      the potential to improve neurologic disease.

PMID- 22990669
TI  - Firing patterns in a conductance-based neuron model: bifurcation, phase diagram,
      and chaos.
AB  - Responding to various stimuli, some neurons either remain resting or can fire
      several distinct patterns of action potentials, such as spiking, bursting,
      subthreshold oscillations, and chaotic firing. In particular, Wilson's
      conductance-based neocortical neuron model, derived from the Hodgkin-Huxley
      model, is explored to understand underlying mechanisms of the firing patterns.
      Phase diagrams describing boundaries between the domains of different firing
      patterns are obtained via extensive numerical computations. The boundaries are
      further studied by standard instability analyses, which demonstrates that the
      chaotic neural firing could develop via period-doubling and/or period- adding
      cascades. Sequences of the firing patterns often observed in many neural
      experiments are also discussed in the phase diagram framework developed. Our
      results lay the groundwork for wider use of the model, especially for
      incorporating it into neural field modeling of the brain.

PMID- 22990668
TI  - Activation of liver X receptors suppresses inflammatory gene expressions and
      transcriptional corepressor clearance in rheumatoid arthritis fibroblast like
      synoviocytes.
AB  - OBJECTIVES: Liver X receptors (LXR) are nuclear receptors that play important
      roles in lipid metabolism and transport. LXR also suppress inflammatory responses
      in macrophages through a unique mechanism of transrepression. This study was
      performed to investigate whether the synthetic LXR agonist GW3965 can modulate
      the inflammatory status of fibroblast-like synoviocytes (FLS) from patients with
      rheumatoid arthritis (RA) and to identify the mechanism for their effect.
      METHODS: RA FLS were treated with 0.1 and 1 MUM of GW3965, a synthetic LXR
      agonist. The mRNA expressions of pro-inflammatory mediators were measured using
      quantitative real-time PCR. Apoptotic cell death of RA FLS was assessed using
      TUNEL assay and determination of caspase-3 activity by a colorimetric assay. The
      levels of transcriptional corepressors including NCoR and SMRT were determined
      using western blot analyses. RESULTS: Treatment of RA FLS with GW3965 induced
      dose-dependent reductions in mRNA expression of pro-inflammatory mediators (IL
      1beta, IL-6, MMP-9, CCL-2, CCL-7, and COX-2). However, treatment with GW3965 at
      the concentration selected for this study had no effect on apoptosis of RA FLS.
      Decreased productions of NCoR and SMRT by LPS stimulation was attenuated by
      GW3965 treatment. CONCLUSIONS: GW3965 treatment suppressed mRNA expressions of
      pro-inflammatory mediators from RA FLS and inhibited the clearance of
      transcriptional corepressors. These data suggest that LXR activation can be used
      as a therapeutic approach to reduce the synovial inflammation in RA.

PMID- 22990670
TI  - Nonviral delivery of small interfering RNA into pancreas-associated immune cells
      prevents autoimmune diabetes.
AB  - The development of small interfering RNA (siRNA) for the treatment of human
      disorders has been often hampered by their low transfection efficiency in vivo.
      In order to overcome this major drawback, various in vivo siRNA transfection
      methods have been developed. However, their capacity to transfect immune or
      insulin-producing beta-cells within the pancreas for the treatment of autoimmune
      diabetes remains undetermined. We found that lipid- or polyethylenimine-based
      delivery agents were efficient to address siRNA molecules within pancreas
      associated antigen-presenting cells (APCs) (but not beta-cells) and particularly
      a CD11b(+) cell population comprising both CD11b(+)CD11c(neg) macrophages and
      CD11b(+)CD11c(+) dendritic cells. However, the route of administration and the
      carrier composition greatly affected the transfection efficacy. Therapeutically,
      we showed that early (starting at 6-week-old) short-course treatment with
      lipid/Alox15-specific siRNA complex promoted long-term protection from type 1
      diabetes (T1D) in wild-type (WT) nonobese diabetic (NOD) mice. Alox15
      downregulation in pancreas-associated CD11b(+) cells significantly upregulated a
      variety of costimulatory molecules and particularly the programmed death 1 ligand
      1 (PD-L1) pathway involved in tolerance induction. Concomitantly, we found that
      regulatory T cells were increased in the pancreas of lipid/Alox15 siRNA-treated
      NOD mice. Collectively, our data provide new insights into the development of
      siRNA-based therapeutics for T1D.

PMID- 22990671
TI  - Ribosomal DNA integrating rAAV-rDNA vectors allow for stable transgene
      expression.
AB  - Although recombinant adeno-associated virus (rAAV) vectors are proving to be
      efficacious in clinical trials, the episomal character of the delivered transgene
      restricts their effectiveness to use in quiescent tissues, and may not provide
      lifelong expression. In contrast, integrating vectors enhance the risk of
      insertional mutagenesis. In an attempt to overcome both of these limitations, we
      created new rAAV-rDNA vectors, with an expression cassette flanked by ribosomal
      DNA (rDNA) sequences capable of homologous recombination into genomic rDNA. We
      show that after in vivo delivery the rAAV-rDNA vectors integrated into the
      genomic rDNA locus 8-13 times more frequently than control vectors, providing an
      estimate that 23-39% of the integrations were specific to the rDNA locus.
      Moreover, a rAAV-rDNA vector containing a human factor IX (hFIX) expression
      cassette resulted in sustained therapeutic levels of serum hFIX even after
      repeated manipulations to induce liver regeneration. Because of the relative
      safety of integration in the rDNA locus, these vectors expand the usage of rAAV
      for therapeutics requiring long-term gene transfer into dividing cells.

PMID- 22990672
TI  - Cetuximab-mediated tumor regression depends on innate and adaptive immune
      responses.
AB  - Epidermal growth factor receptor (EGFR) over-signaling leads to more aggressive
      tumor growth. The antitumor effect of Cetuximab, an anti-EGFR antibody, depends
      on oncogenic-signal blockade leading to tumor cell apoptosis and antibody
      dependent cell-mediated cytotoxicity (ADCC). However, whether adaptive immunity
      plays a role in Cetuximab-mediated tumor inhibition is unclear, as current
      xenograft models lack adaptive immunity and human-EGFR-dependent mouse tumor cell
      lines are unavailable. Using a newly developed xenograft model with reconstituted
      immune cells, we demonstrate that the Cetuximab effect becomes more pronounced
      and reduces the EGFR(+) human tumor burden when adaptive immunity is present. To
      further study this in a mouse tumor model, we created a novel EGFR(+) mouse tumor
      cell line and demonstrated that Cetuximab-induced tumor regression depends on
      both innate and adaptive immunity components, including CD8(+) T cells, MyD88,
      and FcgammaR. To test whether strong innate signals inside tumor tissues
      amplifies the Cetuximab-mediated therapeutic effect, Cetuximab was conjugated to
      CpG. This conjugate is more potent than Cetuximab alone for complete tumor
      regression and resistance to tumor rechallenge. Furthermore, Cetuximab-CpG
      conjugates can activate tumor-reactive T cells for tumor regression by increasing
      dendritic cell (DC) cross-presentation. Therefore, this study establishes new
      models to evaluate immune responses induced by antibody-based treatment, defines
      molecular mechanisms, and provides new tumor-regression strategies.

PMID- 22990673
TI  - AAV vectors containing rDNA homology display increased chromosomal integration
      and transgene persistence.
AB  - Although recombinant adeno-associated viral (rAAV) vectors are promising tools
      for gene therapy of genetic disorders, they remain mostly episomal and hence are
      lost during cell replication. For this reason, rAAV vectors capable of
      chromosomal integration would be desirable. Ribosomal DNA (rDNA) repeat sequences
      are overrepresented during random integration of rAAV. We therefore sought to
      enhance AAV integration frequency by including 28S rDNA homology arms into our
      vector design. A vector containing ~1 kb of homology on each side of a cDNA
      expression cassette for human fumarylacetoacetate hydrolase (FAH) was
      constructed. rAAV of serotypes 2 and 8 were injected into Fah-deficient mice, a
      model for human tyrosinemia type 1. Integrated FAH transgenes are positively
      selected in this model and rDNA-containing AAV vectors had a ~30* higher
      integration frequency than controls. Integration by homologous recombination (HR)
      into the 28S rDNA locus was seen in multiple tissues. Furthermore, rDNA
      containing AAV vectors for human factor IX (hFIX) demonstrated increased
      transgene persistence after liver regeneration. We conclude that rDNA containing
      AAV vectors may be superior to conventional vector design for the treatment of
      genetic diseases, especially those associated with increased hepatocyte
      replication.

PMID- 22990674
TI  - Patterns of scAAV vector insertion associated with oncogenic events in a mouse
      model for genotoxicity.
AB  - Recombinant adeno-associated virus (rAAV) vectors have gained an extensive record
      of safety and efficacy in animal models of human disease. Infrequent reports of
      genotoxicity have been limited to specific vectors associated with excess
      hepatocellular carcinomas (HCC) in mice. In order to understand potential
      mechanisms of genotoxicity, and identify patterns of insertion that could promote
      tumor formation, we compared a self-complementary AAV (scAAV) vector designed to
      promote insertional activation (scAAV-CBA-null) to a conventional scAAV-CMV-GFP
      vector. HCC-prone C3H/HeJ mice and severe combined immunodeficiency (SCID) mice
      were infected with vector plus secondary treatments including partial hepatectomy
      (HPX) and camptothecin (CPT) to determine the effects of cell cycling and DNA
      damage on tumor incidence. Infection with either vector led to a significant
      increase in HCC incidence in male C3H/HeJ mice. Partial HPX after infection
      reduced HCC incidence in the cytomegalovirus-green fluorescent protein (CMV-GFP)
      infected mice, but not in the cognate chicken beta-actin (CBA)-null infected
      group. Tumors from CBA-null infected, hepatectomized mice were more likely to
      contain significant levels of vector DNA than tumors from the corresponding CMV
      GFP-infected group. Most CBA-null vector insertions recovered from tumors were
      associated with known proto-oncogenes or tumor suppressors. Specific patterns of
      insertion suggested read-through transcription, enhancer effects, and disruption
      of tumor suppressors as likely mechanisms for genotoxicity.

PMID- 22990675
TI  - Pharmacological enhancement of alpha-glucosidase by the allosteric chaperone N
      acetylcysteine.
AB  - Pompe disease (PD) is a metabolic myopathy due to the deficiency of the lysosomal
      enzyme alpha-glucosidase (GAA). The only approved treatment for this disorder,
      enzyme replacement with recombinant human GAA (rhGAA), has shown limited
      therapeutic efficacy in some PD patients. Pharmacological chaperone therapy
      (PCT), either alone or in combination with enzyme replacement, has been proposed
      as an alternative therapeutic strategy. However, the chaperones identified so far
      also are active site-directed molecules and potential inhibitors of target
      enzymes. We demonstrated that N-acetylcysteine (NAC) is a novel allosteric
      chaperone for GAA. NAC improved the stability of rhGAA as a function of pH and
      temperature without disrupting its catalytic activity. A computational analysis
      of NAC-GAA interactions confirmed that NAC does not interact with GAA catalytic
      domain. NAC enhanced the residual activity of mutated GAA in cultured PD
      fibroblasts and in COS7 cells overexpressing mutated GAA. NAC also enhanced rhGAA
      efficacy in PD fibroblasts. In cells incubated with NAC and rhGAA, GAA activities
      were 3.7-8.7-fold higher than those obtained in cells treated with rhGAA alone.
      In a PD mouse model the combination of NAC and rhGAA resulted in better
      correction of enzyme activity in liver, heart, diaphragm and gastrocnemia,
      compared to rhGAA alone.

PMID- 22990676
TI  - Myoblasts derived from normal hESCs and dystrophic hiPSCs efficiently fuse with
      existing muscle fibers following transplantation.
AB  - Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells
      (hiPSCs) have an endless self-renewal capacity and can theoretically
      differentiate into all types of lineages. They thus represent an unlimited source
      of cells for therapies of regenerative diseases, such as Duchenne muscular
      dystrophy (DMD), and for tissue repair in specific medical fields. However, at
      the moment, the low number of efficient specific lineage differentiation
      protocols compromises their use in regenerative medicine. We developed a two-step
      procedure to differentiate hESCs and dystrophic hiPSCs in myogenic cells. The
      first step was a culture in a myogenic medium and the second step an infection
      with an adenovirus expressing the myogenic master gene MyoD. Following infection,
      the cells expressed several myogenic markers and formed abundant multinucleated
      myotubes in vitro. When transplanted in the muscle of Rag/mdx mice, these cells
      participated in muscle regeneration by fusing very well with existing muscle
      fibers. Our findings provide an effective method that will permit to use hESCs or
      hiPSCs for preclinical studies in muscle repair.

PMID- 22990677
TI  - Levodopa changes brain motor network function during ankle movements in
      Parkinson's disease.
AB  - Bradykinesia-the cardinal symptom in Parkinson's disease (PD)-affects both upper
      and lower limbs. While several functional imaging studies investigated the impact
      of levodopa on movement-related neural activity in Parkinson's disease during
      upper limb movements, analogue studies on lower limb movements are rare. We
      studied 20 patients with PD (mean age 66.8 +/- 7.2 years) after at least 12 h
      drug withdrawal (OFF-state) and a second time approximately 40 min after oral
      administration of 200 mg levodopa (ON-state) behaviourally and by functional
      magnetic resonance imaging (fMRI) at 3 T during externally cued active ankle
      movements of the more affected foot at fixed rate. Results were compared with
      that obtained in ten healthy controls (HC) to separate pure pharmacological from
      disease-related levodopa-induced effects and to allow for interaction analyses.
      Behaviourally, all patients improved by at least 20 % regarding the motor score
      of the Unified Parkinson's disease rating scale after levodopa-challenge (mean
      scores OFF-state: 38.4 +/- 10.1; ON-state: 25.5 +/- 8.1). On fMRI, levodopa
      application elicited increased activity in subcortical structures (contralateral
      putamen and thalamus) in the patients. In contrast, no significant levodopa
      induced activation changes were found in HC. The interaction between "PD/HC group
      factor" and "levodopa OFF/ON" did not show significant results. Given the
      levodopa-induced activation increases in the putamen and thalamus with unilateral
      ankle movements in patients with PD but not in HC, we speculate that these
      regions show the most prominent response to levodopa within the cortico
      subcortical motor-circuit in the context of nigrostriatal dysfunction.

PMID- 22990679
TI  - Sclerosing rhabdomyosarcoma: report of a case arising in the head and neck of an
      adult and review of the literature.
AB  - Sclerosing rhabdomyosarcoma is a unique rhabdomyosarcoma variant, characterized
      by a prominent hyalinizing matrix. A notable pitfall is the potential for the
      unusual matrix and often pseudovascular growth pattern of this lesion to lead to
      confusion with other sarcoma types, including osteosarcoma, chondrosarcoma, and
      angiosarcoma. Here we report a case of sclerosing rhabdomyosarcoma arising in a
      40-year old male. The tumor was centered in the pterygomaxillary fossa with
      extensive infiltration into adjacent structures. Fine needle aspiration yielded a
      preliminary diagnosis of high-grade pleomorphic undifferentiated sarcoma, for
      which he received neoadjuvant chemotherapy and surgical resection. Microscopic
      examination showed a malignant spindled to round cell neoplasm with prominent
      osteoid-like, hyaline stroma. Focal rhabdomyoblastic differentiation and diffuse
      immunoreactivity for desmin and myogenin aided in diagnosis. Nineteen months
      status post primary resection, the patient expired with multiple lung and bony
      metastases. Among 39 cases reported thus far (including the present case), there
      is a broad age range (0.3-79 years), with an average age at presentation of 27
      years. The most commonly involved sites are the extremities (n = 19) and head and
      neck (n = 15). Most cases have been treated by resection, often combined with
      radiation and/or chemotherapy. Out of 31 cases with follow-up information
      provided, 6 patients developed local recurrence, 7 patients developed regional or
      distant metastasis, and 5 patients died of disease. Herein we discuss the ongoing
      controversy regarding how sclerosing rhabdomyosarcoma might best fit into
      existing rhabdomyosarcoma classification schemes, based upon current
      clinicopathologic and molecular genetic evidence.

PMID- 22990678
TI  - Opposing local effects of endocannabinoids on the activity of noradrenergic
      neurons and release of noradrenaline: relevance for their role in depression and
      in the actions of CB(1) receptor antagonists.
AB  - There is strong evidence that endocannabinoids modulate signaling of serotonin
      and noradrenaline, which play key roles in the pathophysiology and treatment of
      anxiety and depression. Most pharmacological and genetic, human and rodent
      studies suggest that the presence of under-functioning endocannabinoid type-1
      (CB(1)) receptors is associated with increased anxiety and elevated extracellular
      serotonin concentration. In contrast, noradrenaline is presumably implicated in
      the mediation of depression-type symptoms of CB(1) receptor antagonists. Evidence
      shows that most CB(1) receptors located on axons and terminals of GABA-ergic,
      serotonergic or glutamatergic neurons stimulate the activity of noradrenergic
      neurons. In contrast, those located on noradrenergic axons and terminals inhibit
      noradrenaline release efficiently. In this latter process, excitatory ionotropic
      or G protein-coupled receptors, such as the NMDA, alpha1 and beta1 adrenergic
      receptors, activate local endocannabinoid synthesis at postsynaptic sites and
      stimulate retrograde endocannabinoid neurotransmission acting on CB(1) receptors
      of noradrenergic terminals. The underlying mechanisms include calcium signal
      generation, which activates enzymes that increase the synthesis of both
      anandamide and 2-arachidonoylglycerol, while G(q/11) protein activation also
      increases the formation of 2-arachidonoylglycerol from diacylglycerol during the
      signaling process. In addition, other non-CB(1) receptor endocannabinoid targets
      such as CB(2), transient receptor potential vanilloid subtype, peroxisome
      proliferator-activated receptor-alpha and possibly GPR55 can also mediate some of
      the endocannabinoid effects. In conclusion, both neuronal activation and
      neurotransmitter release depend on the in situ synthesized endocannabinoids and
      thus, local endocannabinoid concentrations in different brain areas may be
      crucial in the net effect, namely in the regulation of neurons located
      postsynaptically to the noradrenergic synapse.

PMID- 22990680
TI  - Development of a structured year-end sign-out program in an outpatient continuity
      practice.
AB  - BACKGROUND: In an effort to prevent medical errors, it has been recommended that
      all healthcare organizations implement a standardized approach to communicating
      patient information during transitions of care between providers. Most research
      on these transitions has been conducted in the inpatient setting, with relatively
      few studies conducted in the outpatient setting. OBJECTIVES: To develop a
      structured transfer of care program in an academic outpatient continuity practice
      and evaluate whether this program improved patient safety as measured by the
      documented completion of patient care tasks at 3 months post-transition. DESIGN:
      Graduating residents and the corresponding incoming interns inheriting their
      continuity patient panels were randomized to the pilot structured transfer group
      or the standard transfer group. The structured transfer group residents were
      asked to complete written and verbal sign-outs with their interns; the standard
      transfer group residents continued the current standard of care. PARTICIPANTS:
      Thirty-two resident-intern pairs in an academic internal medicine residency
      program in New York City. MAIN MEASURES: Three months after the transition, study
      investigators evaluated whether patient care tasks assigned by the graduating
      residents had been successfully completed by the interns in both groups. In
      addition, follow-up appointments, continuity of care and house officer
      satisfaction with the sign-out process were evaluated. KEY RESULTS: Among
      patients seen during the first 3 months, the clinical care tasks were more likely
      to be completed by interns in the structured group (73 %, n = 49) versus the
      standard group (46 %, n = 28) (adjusted OR 3.21; 95 % CI 1.55-6.62; p = 0.002).
      This was further enhanced if the intern who saw the patient was also the assigned
      primary care provider (adjusted OR 4.26; 95 % CI 1.7-10.63; p = 0.002).
      CONCLUSIONS: A structured outpatient sign-out improved the odds of follow-up of
      important clinical care tasks after the year-end resident clinic transition.
      Further efforts should be made to improve residents' competency with regard to
      sign-outs in the ambulatory setting.

PMID- 22990681
TI  - Unannounced standardized patient assessment of the roter interaction analysis
      system: the challenge of measuring patient-centered communication.
AB  - BACKGROUND: Despite wide-spread endorsement of patient-centered communication
      (PCC) in health care, there has been little evidence that it leads to positive
      change in health outcomes. The lack of correlation may be due either to an
      overestimation of the value of PCC or to a measurement problem. If PCC measures
      do not capture elements of the interaction that determine whether the resulting
      care plan is patient-centered, they will confound efforts to link PCC to
      outcomes. OBJECTIVE: To evaluate whether one widely used measure of PCC, the
      Roter Interaction Analysis System (RIAS), captures patient-centered care
      planning. DESIGN: RIAS was employed in the coding of unannounced standardized
      patient (USP) encounters that were scripted so that the failure to address
      patient contextual factors would result in an ineffective plan of care. The
      design enabled an assessment of whether RIAS can differentiate between
      communication behavior that does and does not result in a care plan that takes
      into account a patient's circumstances and needs. PARTICIPANTS: Eight actors role
      playing four scripted cases (one African American and one Caucasian for each
      case) in 399 visits to 111 internal medicine attending physicians. MAIN MEASURES:
      RIAS measures included composites for physician utterance types and (in separate
      models) two different previously applied RIAS patient-centeredness summary
      composites. The gold standard comparison measure was whether the physician's
      treatment plan, as abstracted from the visit note, successfully addressed the
      patient's problem. Mixed effects regression models were used to evaluate the
      relationship between RIAS measures and USP measured performance, controlling for
      a variety of design features. KEY RESULTS: None of the RIAS measures of PCC
      differentiated encounters in which care planning was patient-centered from care
      planning in which it was not. CONCLUSIONS: RIAS, which codes each utterance
      during a visit into mutually exclusive and exhaustive categories, does not
      differentiate between conversations leading to and not leading to care plans that
      accommodate patients' circumstances and needs.

PMID- 22990683
TI  - Areal changes of lentic water bodies within an agricultural basin of the
      Argentinean pampas. Disentangling land management from climatic causes.
AB  - Wetland loss is a frequent concern for the environmental management of rural
      landscapes, but poor disentanglement between climatic and land management causes
      frequently constrains both proper diagnoses and planning. The aim of this study
      is to address areal changes induced by non-climatic factors on lentic water
      bodies (LWB) within an agricultural basin of the Argentinean Pampas, and the
      human activities that might be involved. The LWB of the Mar Chiquita basin
      (Buenos Aires province, Argentina) were mapped using Landsat images from 1998
      2008 and then corrected for precipitation variability by considering the regional
      hydrological status on each date. LWB areal changes were statistically and
      spatially analyzed in relation to land use changes, channelization of streams,
      and drainage of small SWB in the catchment areas. We found that 12 % of the total
      LWB in the basin had changed (P < 0.05) due to non-climatic causes. During the
      evaluated decade, 30 % of the LWB that changed size had decreased while 70 %
      showed steady increases in area. The number of altered LWB within watersheds
      lineally increased or decreased according to the proportion of grasslands
      replaced by sown pastures, or the proportion of sown pastures replaced by crop
      fields, respectively. Drainage and channelization do not appear to be related to
      the alteration of LWB; however some of these hydrologic modifications may predate
      1998, and thus earlier effects cannot be discarded. This study shows that large
      scale changes in land cover (e.g., grasslands reduction) can cause a noticeable
      loss of hydrologic regulation at the catchment scale within a decade.

PMID- 22990682
TI  - Inorganic polyphosphate--an unusual suspect of the mitochondrial permeability
      transition mystery.
AB  - Inorganic polyphosphate (polyP) is a naturally occurring polyanion made of ten to
      several hundred orthophosphates (P(i)) linked together by phosphoanhydride bonds.
      PolyP is ubiquitously present in all organisms from bacteria to humans. Specific
      physiological roles of polyP vary dramatically depending on its size,
      concentration, tissue and subcellular localization. Recently we reported that
      mitochondria of ventricular myocytes contain significant amounts (280 +/- 60
      pmol/mg of protein) of polyP with an average length of 25 orthophosphates, and
      that polyP is involved in Ca(2+)-dependent activation of the mitochondrial
      permeability transition pore (mPTP). Here we extend our study to demonstrate the
      involvement of mitochondrial polyP in cardiac cell death. Furthermore, we show
      that polyP levels depend on the activity of the respiratory chain and are lower
      in myocytes from failing hearts. We conclude that polyP is a dynamically
      regulated macromolecule that plays an important role in mPTP-dependent cell death
      pathway.

PMID- 22990684
TI  - Multisensor monitoring system for assessment of locust hazard risk in the Lake
      Balkhash drainage basin.
AB  - Satellite and ground-based data were combined in a monitoring system to quantify
      the link between climate conditions and the risk of locust infestations in the
      southern part of Lake Balkhash's drainage basin in the Republic of Kazakhstan. In
      this monitoring system, the Normalized Difference Vegetation Index (NDVI),
      derived from the SPOT-VGT satellite, was used for mapping potential locust
      habitats and monitoring their area throughout 1998 to 2007. TOPEX/Poseidon and
      Jason 1 altimeter data were used to track the interannual dynamics of water level
      in Balkhash Lake. Climate conditions were represented by weather records for air
      temperature and precipitation during the same period. The classification
      procedure, based on an analysis of multitemporal dynamics of SPOT-VGT NDVI values
      observed by individual vegetation classes, generated annual areas of ten land
      cover types, which were then categorized as areas with low, medium, and high risk
      for locust infestation. Statistical analyses showed significant influences of the
      climatic parameters and the Balkhash Lake hydrological regime on the spatial
      extend of annual areas of potential locust habitats. The results also indicate
      that the linkages between locust infestation risk and environmental factors are
      characterized by time lags. The expansion of locust risk areas are usually
      preceded by dry, hot years and lower water levels in Balkhash Lake when larger
      areas of reed grass are free from seasonal flooding. Years with such conditions
      are favourable for locust outbreaks due to expansion of the habitat areas
      suitable for locust oviposition and nymphal development. In contrast, years with
      higher water levels in Balkhash Lake and lower temperature decrease the potential
      locust habitat area.

PMID- 22990685
TI  - Non-traumatic supraorbital neuralgia: a clinical study of 13 cases.
AB  - INTRODUCTION: Supraorbital neuralgia (SON) is an uncommon disorder characterized
      by pain in the area supplied by the supraorbital nerve, which covers the medial
      aspect of the forehead, together with tenderness over the supraorbital notch or
      along the course of the nerve. Few hospital-based series of non-trauma SON have
      been published. METHODS AND RESULTS: We prospectively analyzed 13 patients (11
      females, two males) diagnosed with SON in a headache outpatient clinic over a
      four-year period. Background pain was mostly dull and of moderate intensity. In
      addition, nine patients reported sharp, burning or stabbing exacerbations of
      severe intensity. Eight cases were treated with an anesthetic blockade and
      achieved complete relief lasting from two to six months. Three patients also
      received gabapentin, with no or only slight improvement. CONCLUSION: Non
      traumatic SON is an uncommon disorder in our headache clinic. Female
      preponderance and clinical features are comparable to the data collected in
      previous studies. A spontaneously remitting pattern is not uncommon, and
      anesthetic blockades are not always required.

PMID- 22990686
TI  - Psychiatric comorbidity in pediatric chronic daily headache.
AB  - OBJECTIVES: The objectives of this study were to assess comorbid psychiatric
      diagnoses in youth with chronic daily headache (CDH) and to examine relationships
      between psychiatric status and CDH symptom severity, as well as headache-related
      disability. METHODS: Standardized psychiatric interviews (Kiddie Schedule for
      Affective Disorders and Schizophrenia, KSADS) were conducted with 169 youth ages
      10-17 diagnosed with CDH. Participants provided prospective reports of headache
      frequency with a daily headache diary and completed measures of symptom severity,
      headache-related disability (PedMIDAS) and quality of life (PedsQL). RESULTS:
      Results showed that 29.6% of CDH patients met criteria for at least one current
      psychiatric diagnosis, and 34.9% met criteria for at least one lifetime
      psychiatric diagnosis. No significant relationship between psychiatric status and
      headache frequency, duration, or severity was found. However, children with at
      least one lifetime psychiatric diagnosis had greater functional disability and
      poorer quality of life than those without a psychiatric diagnosis. DISCUSSION:
      Contrary to research in adults with chronic headaches, most youth with CDH did
      not appear to be at an elevated risk for comorbid psychiatric diagnosis. However,
      patients with a comorbid psychiatric diagnosis were found to have higher levels
      of headache-related disability and poorer quality of life. Implications for
      treatment are discussed.

PMID- 22990687
TI  - Comparison of the radioisotope cisternography findings of spontaneous
      intracranial hypotension and iatrogenic cerebrospinal fluid leakage focusing on
      chronological changes.
AB  - BACKGROUND: Radioisotope cisternography (RICG) is useful for detecting
      cerebrospinal fluid (CSF) leakage in spontaneous intracranial hypotension (SIH)
      patients. However, RICG can cause iatrogenic CSF leakage (ICSFL) due to a lumbar
      puncture. OBJECTIVES: To compare the RICG findings of SIH and ICSFL. METHODS: The
      presence of direct findings suggesting CSF leakage and indirect findings
      including early visualization of the bladder and absence of radioactivity over
      the brain convexities were evaluated in seven SIH and six ICSFL patients.
      Radioisotope clearance was assessed semi-quantitatively. RESULTS: In contrast to
      the variety of anatomical levels at which direct findings were detected in the
      SIH patients, the ICSFL patients only displayed direct findings at the
      lumbosacral level. None of the ICSFL patients displayed direct findings at 1 hour
      after the tracer injection. Although early visualization of the bladder was
      depicted in all patients, no activity was visualized over the brain convexities
      in the SIH patients. In the semi-quantitative analysis, the tracer retention
      index at 24 hours was lower in the SIH patients than the ICSFL patients.
      CONCLUSIONS: The early appearance of direct findings above the lumbosacral level,
      the absence of radioactivity over the brain convexities and a low tracer
      retention index are suggestive of SIH.

PMID- 22990688
TI  - Status migrainosus as a potential stressor leading to takotsubo cardiomyopathy.
AB  - BACKGROUND: Takotsubo cardiomyopathy is a form of non-ischemic cardiomyopathy
      that may be acutely precipitated by stress. A number of neurologic conditions
      have been implicated in precipitating this disease such as subarachnoid
      hemorrhage, stroke, and seizures. Its association with status migrainosus,
      however, has never been described before. CASE: We report a case of a 25-year-old
      female presenting with status migrainosus followed by takotsubo cardiomyopathy.
      Supportive management was instituted in this patient and she made an excellent
      recovery. CONCLUSION: The intense pain associated with migraine may have acted as
      a stressor, thereby precipitating takotsubo cardiomyopathy. To our knowledge,
      this is the first reported case demonstrating a relationship between status
      migrainosus and takotsubo cardiomyopathy.

PMID- 22990689
TI  - Transient visual disturbances in adolescents: migrainous feature or headache
      accompanied phenomenon?
AB  - OBJECTIVES: To investigate the prevalence, characteristics and clinical
      correlates of transient visual disturbances (TVDs) in adolescents with headaches.
      METHODS: We surveyed headache-related TVDs in the past three months in two middle
      schools. All the ninth-grade students filled-in the questionnaires including
      demographics, a validated headache questionnaire, and visual phenomenon questions
      embedding the Visual Aura Rating Scale (VARS). TVDs were defined as transient
      visual phenomena corresponding to a headache attack, but not visual aura, i.e.
      VARS <four. RESULTS: Six hundred and sixty-three adolescents (341 boys and 322
      girls; mean age 15.1 +/- 0.3 years old) participated in this study. In subjects
      reporting at least one headache during the past three months (N = 371), 33.4%
      reported TVDs, which accounted for 18.7% in total participants. TVDs were
      described mainly as flickering lights or scotoma, movable, monochromatic,
      occurring over bilateral visual fields, developing and lasting <30 seconds, and
      experienced during the headache phase. Subjects with migraines reported a higher
      frequency of TVDs than those with non-migraine headaches (67.1% vs. 31.2%, p <
      0.001). TVDs were independently associated with photophobia (OR = 12.6, p <
      0.001) and pulsatile headache (OR = 2.1, p = 0.012). CONCLUSIONS: The major
      features of TVDs were distinguishable from visual aura. TVDs were common in
      adolescents with headaches, especially in migraineurs.

PMID- 22990690
TI  - Botulinum toxin for trigeminal neuralgia--do we have the evidence?

PMID- 22990712
TI  - Complement in Action: An Analysis of Patent Trends from 1976 Through 2011.
AB  - Complement is an essential part of the innate immune response. It interacts with
      diverse endogenous pathways and contributes to the maintenance of homeostasis,
      the modulation of adaptive immune responses, and the development of various
      pathologies. The potential usefulness, in both research and clinical settings, of
      compounds that detect or modulate complement activity has resulted in thousands
      of publications on complement-related innovations in fields such as drug
      discovery, disease diagnosis and treatment, and immunoassays, among others. This
      study highlights the distribution and publication trends of patents related to
      the complement system that were granted by the United States Patent and Trademark
      Office from 1976 to the present day. A comparison to complement-related documents
      published by the World Intellectual Property Organization is also included.
      Statistical analyses revealed increasing diversity in complement-related research
      interests over time. More than half of the patents were found to focus on the
      discovery of inhibitors; interest in various inhibitor classes exhibited a
      remarkable transformation from chemical compounds early on to proteins and
      antibodies in more recent years. Among clinical applications, complement proteins
      and their modulators have been extensively patented for the diagnosis and
      treatment of eye diseases (especially age-related macular degeneration), graft
      rejection, cancer, sepsis, and a variety of other inflammatory and immune
      diseases. All of the patents discussed in this chapter, as well as those from
      other databases, are available from our newly constructed complement patent
      database: www.innateimmunity.us/patent .

PMID- 22990713
TI  - Time resolved polarization dependent single shot four wave mixing.
AB  - Single shot time resolved four wave mixing is a powerful tool for the acquisition
      of dynamic and spectroscopic data from molecules susceptible to bleaching or
      other photo-induced damage. We add polarization dependence to single shot
      methods, and demonstrate how magic angle measurements are made simpler by this
      methodology. We propose a new approach to single shot combined time/polarization
      measurements which can be generalized to other two dimensional combinations.

PMID- 22990692
TI  - Progress and Trends in Complement Therapeutics.
AB  - The past few years have proven to be a highly successful and exciting period for
      the field of complement-directed drug discovery and development. Driven by
      promising experiences with the first marketed complement drugs, increased
      knowledge about the involvement of complement in health and disease, and
      improvements in structural and analytical techniques as well as animal models of
      disease, the field has seen a surge in creative approaches to therapeutically
      intervene at various stages of the cascade. An impressive panel of compounds that
      show promise in clinical trials is meanwhile being lined up in the pipelines of
      both small biotechnology and big pharmaceutical companies. Yet with this new
      focus on complement-targeted therapeutics, important questions concerning target
      selection, point and length of intervention, safety, and drug delivery emerge. In
      view of the diversity of the clinical disorders involving abnormal complement
      activity or regulation, which include both acute and chronic diseases and affect
      a wide range of organs, diverse yet specifically tailored therapeutic approaches
      may be needed to shift complement back into balance. This chapter highlights the
      key changes in the field that shape our current perception of complement-targeted
      drugs and provides a brief overview of recent strategies and emerging trends.
      Selected examples of complement-related diseases and inhibitor classes are
      highlighted to illustrate the diversity and creativity in field.

PMID- 22990714
TI  - CanMEDS and other "competency and outcome-based approaches" in medical education:
      clarifying the ongoing ambiguity.

PMID- 22990717
TI  - Identifying protein quaternary structural attributes by incorporating
      physicochemical properties into the general form of Chou's PseAAC via discrete
      wavelet transform.
AB  - In vivo, some proteins exist as monomers and others as oligomers. Oligomers can
      be further classified into homo-oligomers (formed by identical subunits) and
      hetero-oligomers (formed by different subunits), and they form the structural
      components of various biological functions, including cooperative effects,
      allosteric mechanism and ion-channel gating. Therefore, with the avalanche of
      protein sequences generated in the post-genomic era, it is very important for
      both basic research and the pharmaceutical industry to acquire the possible
      knowledge about quaternary structural attributes of their proteins of interest.
      In view of this, a high throughput method (DWT_DT), a 2-layer approach by fusing
      discrete wavelet transform (DWT) and decision-tree algorithm (DT) with
      physicochemical features, has been developed to predict protein quaternary
      structures. The 1st layer is to assign a query protein to one of the 10 main
      quaternary structural attributes. The 2nd layer is to evaluate whether the
      protein in question is composed of homo- or hetero-oligomers. The overall
      accuracy by jackknife test for the 1st layer identification was 89.60%. The
      overall accuracy of the 2nd layer varies from 88.23 to 100%. The results suggest
      that this newly developed protocol (DWT_DT) is very promising in predicting
      quaternary structures with complicated composition.

PMID- 22990716
TI  - Acarbose treatment enhances mid-regional pro-atrial natriuretic peptide
      concentrations in non-diabetic individuals: further evidence for a common
      cardiometabolic pathway?

PMID- 22990715
TI  - Clinical evolution of beta cell function in youth with diabetes: the SEARCH for
      Diabetes in Youth study.
AB  - AIMS/HYPOTHESIS: Few studies have explored the epidemiology of beta cell loss in
      youth with diabetes. This report describes the evolution and major determinants
      of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for
      Diabetes in Youth study. METHODS: Participants were 1,277 youth with diabetes
      (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs),
      diagnosed when aged <20 years, who were followed from a median of 8 months post
      diagnosis, for approximately 30 months. We modelled the relationship between rate
      of change in log FCP and determinants of interest using repeated measures general
      linear models. RESULTS: Among DA-positive youth, there was a progressive decline
      in beta cell function of 4% per month, independent of demographics (age, sex,
      race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and
      BMI z score, or presence of insulin resistance. Among DA-negative youth, there
      was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed
      group. This group likely includes youths with undetected autoimmunity (whose
      decline is similar to that of DA-positive youth) and youth with non-autoimmune,
      insulin-resistant diabetes, with limited decline (~0.7% per month).
      CONCLUSIONS/INTERPRETATION: SEARCH provides unique estimates of beta cell
      function decline in a large sample of youth with diabetes, indicating that
      autoimmunity is the major contributor. These data contribute to a better
      understanding of clinical evolution of beta cell function in youth with diabetes,
      provide strong support for the aetiological classification of diabetes type and
      may inform tertiary prevention efforts targeted at high-risk groups.

PMID- 22990718
TI  - Anti-GAD positive stiff-person syndrome and cerebellar ataxia: two treatable
      conditions that clinicians should be aware of.

PMID- 22990719
TI  - Neurological disorders associated with glutamic acid decarboxylase antibodies: a
      Brazilian series.
AB  - Neurological disorders associated with glutamic acid decarboxylase (GAD)
      antibodies are rare pleomorphic diseases of uncertain cause, of which stiff
      person syndrome (SPS) is the best-known. Here, we described nine consecutive
      cases of neurological disorders associated with anti-GAD, including nine patients
      with SPS and three cases with cerebellar ataxia. Additionally, four had
      hypothyroidism, three epilepsy, two diabetes mellitus and two axial myoclonus.

PMID- 22990720
TI  - Clinical features and treatment with botulinum toxin in blepharospasm: a 17-year
      experience.
AB  - OBJECTIVE: It was to analyze clinical aspects of patients with blepharospasm,
      including outcomes of botulinum toxin treatment. Additionally, clinical
      characteristics of isolated blepharospasm were compared to those of blepharospasm
      plus other movement disorders. METHODS: Clinical data recorded during 17 years
      were reviewed. The variables included age, gender, age of onset, past medical
      history, head trauma, smoking history, family history of dystonia, severity,
      duration of botulinum toxin relief and adverse effects. RESULTS: A total of 125
      patients were included and 75.2% were female. The mean age of onset was 54.3
      years; 89.6% of the individuals started with contractions in eye region, and
      39.2% of them spread to lower face or neck. Isolated blepharospasm group was
      compared with blepharospasm-plus group for demographic and clinical features, and
      therapeutic outcomes, without significant differences. Botulinum toxin treatment
      improved the severity of contractions (p=0.01) with low rate of side effects
      (14%). CONCLUSIONS: Both groups - isolated blepharospasm and blepharospasm-plus -
      shared similar results concerning epidemiology, clinical features and therapeutic
      response to botulinum toxin.

PMID- 22990721
TI  - Dopamine transporter imaging in clinically unclear cases of parkinsonism and the
      importance of scans without evidence of dopaminergic deficit (SWEDDs).
AB  - The clinical diagnosis of Parkinson's disease (PD) is susceptible to
      misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo
      imaging techniques assessing the presynaptic dopamine transporter (DAT) have
      emerged as a useful tool in PD diagnosis, improving its accuracy. OBJECTIVE: It
      was to illustrate the clinical usefulness of a brain single-photon emission
      computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans
      without evidence of dopaminergic deficit (SWEDDs) in this context. CASES: We
      described four representative patients with clinically unclear parkinsonian
      syndromes who underwent [(99m)Tc]-TRODAT-1 SPECT and reviewed the clinical
      implications. CONCLUSION: DAT-SPECT is an important, cost-effective, technique
      for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD
      cases present clinical and paraclinical peculiarities that may retrospectively
      identify them as essential/dystonic tremor. The lack of histopathological data
      limits further conclusions.

PMID- 22990722
TI  - Idiopathic Parkinson's disease: vocal and quality of life analysis.
AB  - OBJECTIVE: To compare voice and life quality of male patients with idiopathic
      Parkinson's disease, with individuals without disease (Control Group). METHODS: A
      cross-sectional study that evaluated the voice of individuals with Parkinson's
      disease, the group was composed of 27 subjects, aged from 39 to 79 years-old
      (average 59.96). The Control Group was matched on sex and age. Participants
      underwent voice recording. Perceptual evaluation was made using GRBASI scale,
      which considers G as the overall degree of dysphonia, R as roughness, B as
      breathiness, A as asthenia, S as strain and I as instability. The acoustic
      parameters analyzed were: fundamental frequency, jitter, shimmer, and harmonic to
      noise ratio (NHR). For vocal self-perception analysis, we used the Voice Related
      Quality of Life protocol. RESULTS: Fundamental frequency and jitter presented
      higher values in the Parkinson's group. NHR values were higher in the Control
      Group. Perceptual analysis showed a deviation ranging. The vocal disorder self
      perception demonstrated a worse impact on quality of life. CONCLUSIONS:
      Individuals with Parkinson's disease have an altered voice quality and a negative
      impact on quality of life.

PMID- 22990723
TI  - Effects of Daoyin Qigong in postpolio syndrome patients with cold intolerance.
AB  - Postpolio syndrome (PPS) is characterized by progressive muscle weakness due to
      former infection with poliomyelitis and can be associated with other symptoms
      such as cold intolerance (CI). Daoyin Qigong (DQ) is a technique in Traditional
      Chinese Medicine that impacts the circulation of energy and blood. OBJECTIVE: It
      was to verify the effects of DQ in PPS patients complaining of cold intolerance.
      METHODS: Ten PPS patients were assessed using the visual analogue scale (VAS)
      adapted for CI before and after intervention with DQ; patients practiced it in a
      sitting position for 40 minutes, 3 times per week over 3 consecutive months.
      Patients were reassessed three months after ceasing DQ. RESULTS: There was a
      statistically significant difference in local and systemic VAS-Cold both at the
      end of DQ training and three months past the end of this. CONCLUSION: The DQ
      technique ameliorated CI complaints in patients with PPS.

PMID- 22990724
TI  - Difficulties in HAM/TSP diagnosis.
AB  - The World Health Organization recommends the use of Osame's criterion (1990) for
      the diagnosis of HTLV-I-associated myelopathy (HAM/TSP). In 2006, a group of
      neurologists developed a Brazilian criterion that can diagnose HAM/TSP from its
      onset. OBJECTIVE: It was to test the agreement between both criteria. METHODS:
      The study included evaluation of clinical and laboratory findings of 35 patients.
      The ELISA, Western blot and/or polymerase chain reaction was used to search for
      anti-HTLV-I antibodies. The analysis of agreement was based on the calculation of
      Kappa. RESULTS: Concordance of 100% (Kappa=1) occurred in cases of "defined"
      HAM/TSP, but not in patients with "probable" diagnosis. CONCLUSION: The Brazilian
      criteria was as effective as Osame's criteria for the diagnosis of "defined"
      HAM/TSP. However, both require more specific biological markers in cerebrospinal
      fluid for the laboratory diagnosis of probable cases.

PMID- 22990725
TI  - Clinical and neuropsychological correlation in patients with rolandic epilepsy.
AB  - OBJECTIVES: To evaluate the presence of neurological soft signs (NSS) and to
      correlate them with the Wechsler Intelligence Scale for Children (WISC III) in
      patients with rolandic epilepsy (RE). METHODS: Forty children and adolescents
      aged between 9 and 15 years were studied. They were divided into two groups: G1 -
      patients with RE (n=20) - and G2 - healthy controls without epilepsy (n=20). They
      were assessed with the Quick Neurological Screening Test (QNST II) - clinical
      trial to search for NSS -, and the WISC III - neuropsychological test. RESULTS:
      No statistical difference between groups was found in WISC III and QNST II.
      However, children with poorer motor skills had worse performance in the QNST II
      and also in the execution intelligence quotient - IQ (p=0.001) and in total IQ
      (p=0.004), thus showing a positive correlation between them. CONCLUSIONS: The
      QNST II is a good screening tool for the neurologist to detect abnormalities in
      fine motor skills.

PMID- 22990726
TI  - Relationship of number of seizures recorded on video-EEG to surgical outcome in
      refractory medial temporal lobe epilepsy.
AB  - INTRODUCTION: Surgical planning for refractory medial temporal lobe epilepsy
      (rMTLE) relies on seizure localization by ictal electroencephalography (EEG).
      Multiple factors impact the number of seizures recorded. We evaluated whether
      seizure freedom correlated to the number of seizures recorded, and the related
      factors. METHODS: We collected data for 32 patients with rMTLE who underwent
      anterior temporal lobectomy. Primary analysis evaluated number of seizures
      captured as a predictor of surgical outcome. Subsequent analyses explored factors
      that may seizure number. RESULTS: Number of seizures recorded did not predict
      seizure freedom. More seizures were recorded with more days of seizure occurrence
      (p<0.001), seizure clusters (p<=0.011) and poorly localized seizures (PLSz)
      (p=0.004). Regression modeling showed a trend for subjects with fewer recorded
      poorly localized seizures to have better surgical outcome (p=0.052). CONCLUSIONS:
      Total number of recorded seizures does not predict surgical outcome. Patients
      with more PLSz may have worse outcome.

PMID- 22990727
TI  - Neurological complications following bariatric surgery.
AB  - OBJECTIVE: It was to report on Brazilian cases of neurological complications from
      bariatric surgery. The literature on the subject is scarce. METHOD: Cases
      attended by neurologists in eight different Brazilian cities were collected and
      described in the present study. RESULTS: Twenty-six cases were collected in this
      study. Axonal polyneuropathy was the most frequent neurological complication, but
      cases of central demyelination, Wernicke syndrome, optical neuritis, radiculits,
      meralgia paresthetica and compressive neuropathies were also identified. Twenty
      one patients (80%) had partial or no recovery from the neurological signs and
      symptoms. CONCLUSION: Bariatric surgery, a procedure that is continuously
      increasing in popularity, is not free of potential neurological complications
      that should be clearly presented to the individual undergoing this type of
      surgery. Although a clear cause-effect relation cannot be established for the
      present cases, the cumulative literature on the subject makes it important to
      warn the patient of the potential risks of this procedure.

PMID- 22990728
TI  - Performance of fixed-pressure valve with antisiphon device SPHERA((r)) in
      hydrocephalus treatment and overdrainage prevention.
AB  - Patients with hydrocephalus and risk factors for overdrainage may be submitted to
      ventricular shunt (VS) implant with antisiphon device. The objective of this
      study was to prospectively evaluate for two years the clinical and tomographic
      results of the implant of fixed-pressure valves with antisiphon device
      SPHERA((r)) in 35 adult patients, with hydrocephalus and risk factors for
      overdrainage. Of these, 3 had congenital hydrocephalus in adult patients with
      very dilated ventricles (Evans index >50%), 3 had symptomatic overdrainage after
      previous VS implant (subdural hematoma, hygroma or slit ventricle syndrome), 1
      had previous chronic subdural hematoma, 15 had normal pressure hydrocephalus with
      final lumbar pressure <5 cm H(2)O after tap test (40 mL), 6 had pseudotumor
      cerebri, and 7 had hydrocephalus due to other causes. Clinical improvement was
      observed and sustained in 94.3% of the patients during the two-year period with
      no computed tomography (CT) evidence of hypo or overdrainage, and no immediate
      early or late significant complications.

PMID- 22990729
TI  - Dysembryoplastic neuroepithelial tumor originally diagnosed as astrocytoma and
      oligodendroglioma.
AB  - Dysembryoplastic neuroepithelial tumor (DNT), described in 1988 and introduced in
      the WHO classification in 1993, affects predominantly children or young adults
      causing intractable complex partial seizures. Since it is benign and treated with
      surgical resection, its recognition is important. It has similarities with low
      grade gliomas and gangliogliomas, which may recur and become malignant.
      OBJECTIVES: To investigate whether DNT was previously diagnosed as astrocytoma,
      oligodendroglioma, or ganglioglioma and to determine its frequency in a series of
      low-grade glial/glio-neuronal tumors. METHODS: Clinical, radiological, and
      histological aspects of 58 tumors operated from 1978 to 2008, classified as
      astrocytomas (32, including 8 pilocytic), oligodendrogliomas (12), gangliogliomas
      (7), and DNT (7), were reviewed. RESULTS: Four new DNT, one operated before 1993,
      previously classified as astrocytoma (3) and oligodendroglioma (1), were
      identified. One DNT diagnosed in 2002 was classified once more as angiocentric
      glioma. Therefore, 10 DNT (17.2%) were identified. CONCLUSIONS: Clinical
      radiological and histopathological correlations have contributed to diagnose the
      DNT.

PMID- 22990730
TI  - New algorithm for the diagnosis of hereditary dystonia.
AB  - Taking into account the crescent interest in the field of dystonia genetics, we
      have organized a didactic and fast algorithm to diagnose the main forms of
      hereditary dystonias. The key branch of this algorithm is pointed to dystonia
      classification in primary, plus, or paroxysmal. The specific characteristics of
      each syndrome will reveal the diagnosis.

PMID- 22990731
TI  - Lexical-semantic processing in the semantic priming paradigm in aphasic patients.
AB  - There is evidence that the explicit lexical-semantic processing deficits which
      characterize aphasia may be observed in the absence of implicit semantic
      impairment. The aim of this article was to critically review the international
      literature on lexical-semantic processing in aphasia, as tested through the
      semantic priming paradigm. Specifically, this review focused on aphasia and
      lexical-semantic processing, the methodological strengths and weaknesses of the
      semantic paradigms used, and recent evidence from neuroimaging studies on lexical
      semantic processing. Furthermore, evidence on dissociations between implicit and
      explicit lexical-semantic processing reported in the literature will be discussed
      and interpreted by referring to functional neuroimaging evidence from healthy
      populations. There is evidence that semantic priming effects can be found both in
      fluent and in non-fluent aphasias, and that these effects are related to an
      extensive network which includes the temporal lobe, the pre-frontal cortex, the
      left frontal gyrus, the left temporal gyrus and the cingulated cortex.

PMID- 22990732
TI  - The pterional craniotomy: tips and tricks.
AB  - This review intended to describe in a didactic and practical manner the
      frontotemporosphenoidal craniotomy, which is usually known as pterional
      craniotomy and constitute the cranial approach mostly utilized in the modern
      neurosurgery. This is, then, basically a descriptive text, divided according to
      the main stages involved in this procedure, and describes with details how the
      authors currently perform this craniotomy.

PMID- 22990733
TI  - Physiopathology of symptoms and signs in multiple sclerosis.
AB  - The physiopathology of symptoms and signs in multiple sclerosis (MS) is a less
      divulged topic albeit its importance in the patients' management. OBJECTIVE: It
      was to summarize the main biophysical and biochemical mechanisms which produce
      the clinical manifestations in MS. RESULTS: The mechanisms underpinning
      neurological deficits are described in the relapsing and in the progressive
      phases, stressing inflammatory and neurodegenerative components, especially
      demyelination, axonal damage and conduction impairment. Transient worsening based
      in Uhthoff's phenomenon, mechanisms producing positive symptoms, as paraesthesias
      and Lhermitte sign due to axonal hyperexcitability and ephaptic interactions, and
      development of cortical symptoms will also be addressed. The variety of processes
      leading to neural repair and functional recovery in the remitting phase is
      focused, as remyelination and adaptive changes due to neural plasticity.
      CONCLUSION: The awareness of mechanisms producing symptoms in MS emphasises the
      role of symptomatic and rehabilitation therapies in the improvement of patients'
      well-being.

PMID- 22990734
TI  - Takayasu's arteritis and cerebral venous thrombosis: comorbidity or coincidence?

PMID- 22990735
TI  - Cervical and axial dystonia in a patient with syringomyelia.

PMID- 22990736
TI  - Ectopic growth hormone-secreting pituitary adenoma involving the clivus treated
      with octreotide: role of magnetic resonance imaging in the diagnosis and clinical
      follow-up.

PMID- 22990737
TI  - Ganglioglioma with anaplastic transformation.

PMID- 22990738
TI  - Should topiramate use be added to the differential diagnosis of visual illusions?

PMID- 22990739
TI  - Severe dystonia as the first manifestation of neuromyelitis optica.

PMID- 22990740
TI  - Neurocysticercosis, immune status and immune response.

PMID- 22990745
TI  - UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and
      with altered neuroblastoma cell proliferation and sensitivity to epidermal growth
      factor receptor inhibitors.
AB  - BACKGROUND: The UBE4B gene, which is located on chromosome 1p36, encodes a
      ubiquitin ligase that interacts with hepatocyte growth factor-regulated tyrosine
      kinase substrate (Hrs), a protein involved in epidermal growth factor receptor
      (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma
      pathogenesis. The authors analyzed the roles of UBE4B in the outcomes of patients
      with neuroblastoma and in neuroblastoma tumor cell proliferation, EGFR
      trafficking, and response to EGFR inhibition. METHODS: The association between
      UBE4B expression and the survival of patients with neuroblastoma was examined
      using available microarray data sets. UBE4B and EGFR protein levels were measured
      in patient tumor samples, EGFR degradation rates were measured in neuroblastoma
      cell lines, and the effects of UBE4B on neuroblastoma tumor cell growth were
      analyzed. The effects of the EGFR inhibitor cetuximab were examined in
      neuroblastoma cells that expressed wild-type and mutant UBE4B. RESULTS: Low UBE4B
      gene expression is associated with poor outcomes in patients with neuroblastoma.
      UBE4B overexpression reduced neuroblastoma tumor cell proliferation, and UBE4B
      expression was inversely related to EGFR expression in tumor samples. EGFR
      degradation rates correlated with cellular UBE4B levels. Enhanced expression of
      catalytically active UBE4B resulted in reduced sensitivity to EGFR inhibition.
      CONCLUSIONS: The current study demonstrates associations between UBE4B expression
      and the outcomes of patients with neuroblastoma and between UBE4B and EGFR
      expression in neuroblastoma tumor samples. Moreover, levels of UBE4B influence
      neuroblastoma tumor cell proliferation, EGFR degradation, and response to EGFR
      inhibition. These results suggest UBE4B-mediated growth factor receptor
      trafficking may contribute to the poor prognosis of patients who have
      neuroblastoma tumors with 1p36 deletions and that UBE4B expression may be a
      marker that can predict responses of neuroblastoma tumors to treatment.

PMID- 22990746
TI  - Parental coping in the neonatal intensive care unit.
AB  - Fifty-six mothers of premature infants who participated in a study to reduce
      symptoms of posttraumatic stress disorder (PTSD) completed the Brief COPE, a self
      report inventory of coping mechanisms, the Stanford Acute Stress Reaction
      Questionnaire to assess acute stress disorder (ASD) and the Davidson Trauma Scale
      to assess PTSD. 18 % of mothers had baseline ASD while 30 % of mothers met the
      criteria for PTSD at the 1-month follow-up. Dysfunctional coping as measured by
      the Brief COPE was positively associated with elevated risk of PTSD in these
      mothers (RR = 1.09, 95 % CI 1.02-1.15; p = .008). Maternal education was
      positively associated with PTSD; each year increase in education was associated
      with a 17 % increase in the relative risk of PTSD at 1 month follow-up (RR =
      1.17, 95 % CI 1.02-1.35; p = .03). Results suggest that dysfunctional coping is
      an important issue to consider in the development of PTSD in parents of premature
      infants.

PMID- 22990747
TI  - A comparison of enrollees versus non-enrollees in a patient/family HCV
      psychoeducation study.
AB  - Despite the seriousness of Hepatitis C (HCV), many patients do not receive
      treatment. One promising means of addressing these issues for medically ill
      patients is through participation in support group services. This study examined
      individual-, treatment- and system-level factors associated with enrolling in a
      support group intervention (psychoeducation) for persons with HCV. A total of 235
      research participants were recruited as part of a NIAAA-funded randomized
      clinical trial for patients with HCV and their family members, with 172 (73.2 %)
      agreeing to enroll in the psychoeducation trial and 63 (26.8 %) declining.
      Factors leading to enrollment indicated that individuals without employment, with
      certain personality structures (low cooperativeness and self-directedness), and
      traveling greater distance to their group were more likely to agree to
      participate. Populations being seen in public settings demonstrate a desire for
      additional support and education, but at the same time these potential
      participants are faced with challenges to following through and enrolling in the
      desired services.

PMID- 22990749
TI  - Glomalin: an arbuscular mycorrhizal fungal soil protein.
AB  - Glomalin is abundant in soils and is closely correlated with aggregate water
      stability. Glomalin contains carbon and, hence, constitutes a non-trivial portion
      of the terrestrial carbon pool. Possibly far more importantly, however,
      stabilization of aggregates amplifies the role of glomalin in soils because
      carbonaceous compounds are protected from degradation inside of aggregates.
      Increased atmospheric CO2 can lead to increased production of glomalin because of
      the symbiotic association that exists between plants and producers of glomalin,
      arbuscular mycorrhizal fungi (AMF). Glomalin concentrations in soils are
      influenced by management practices, for example, in agroecosystems, further
      highlighting the role of this protein in carbon storage. Glomalin is an unusual
      molecule that has proven difficult to analyze biochemically due to its
      recalcitrance and complexity. Future research will be directed towards the
      elucidation of its structure and controls on its production.

PMID- 22990750
TI  - A clinician-driven automated system for integration of pharmacogenetic
      interpretations into an electronic medical record.

PMID- 22990752
TI  - The TGF-beta pathway as an emerging target for Chagas disease therapy.
AB  - Transforming growth factor-beta (TGF-beta) influences the development of
      myocardiopathy in Chagas disease through regulation of (i) parasite invasion of
      heart cells, (ii) an intracellular parasite cycle, (iii) inflammation and immune
      response, (iv) heart fibrosis and remodeling, and (v) gap junction modulation and
      heart conduction. In this review, we discuss the rationale for developing TGF
      beta signaling-interfering therapies as adjuvant approaches for the management of
      the cardiac alterations of Chagas disease-affected patients.

PMID- 22990751
TI  - OATP1B1 polymorphism as a determinant of erythromycin disposition.
AB  - Previous studies have demonstrated that the pharmacokinetic profile of
      erythromycin, a probe for CYP3A4 activity, is affected by inhibitors or inducers
      of hepatic solute carriers. We hypothesized that these interactions are mediated
      by OATP1B1 (gene symbol, SLCO1B1), a polypeptide expressed on the basolateral
      surface of hepatocytes. Using stably transfected Flp-In T-Rex293 cells,
      erythromycin was found to be a substrate for OATP1B1*1A (wild type) with a
      Michaelis-Menten constant of ~13 umol/l, and that its transport was reduced by
      ~50% in cells expressing OATP1B1*5 (V174A). Deficiency of the ortholog
      transporter Oatp1b2 in mice was associated with a 52% decrease in the metabolic
      rate of erythromycin (P = 0.000043). In line with these observations, in humans
      the c.521T>C variant in SLCO1B1 (rs4149056), encoding OATP1B1*5, was associated
      with a decline in erythromycin metabolism (P = 0.0072). These results suggest
      that impairment of OATP1B1 function can alter erythromycin metabolism,
      independent of changes in CYP3A4 activity.

PMID- 22990753
TI  - Methane storage in advanced porous materials.
AB  - The need for alternative fuels is greater now than ever before. With considerable
      sources available and low pollution factor, methane is a natural choice as
      petroleum replacement in cars and other mobile applications. However, efficient
      storage methods are still lacking to implement the application of methane in the
      automotive industry. Advanced porous materials, metal-organic frameworks and
      porous organic polymers, have received considerable attention in sorptive storage
      applications owing to their exceptionally high surface areas and chemically
      tunable structures. In this critical review we provide an overview of the current
      status of the application of these two types of advanced porous materials in the
      storage of methane. Examples of materials exhibiting high methane storage
      capacities are analyzed and methods for increasing the applicability of these
      advanced porous materials in methane storage technologies described.

PMID- 22990754
TI  - Higher endogenous estrogen levels in 70-year-old women and men:  an endogenous
      response to counteract developing atherosclerosis?
AB  - OBJECTIVE: Reported associations between endogenous steroid hormone levels and
      cardiovascular disease in the older population have been contradictory. We
      evaluated plasma steroid concentrations in terms of the dimensions of the common
      carotid artery wall layers as a measure of the extent of atherosclerosis.
      METHODS: A subgroup of 70-year-old participants (32 women and 50 men) from the
      Prospective Investigation of the Vasculature in Uppsala Seniors study was
      investigated. All participants had assessments of common carotid artery wall
      layer parameters (intima thickness, media thickness, and intima-media thickness
      [IMT] ratio; measured by high-frequency ultrasound at 22 MHz) and endogenous
      steroid hormone concentrations (measured by liquid chromatography-tandem mass
      spectrometry). RESULTS: Low androgen levels, high aromatase enzyme activity
      (estrone [E1]/androstenedione and estradiol [E2]/testosterone), high E2/E1 ratio,
      and high estrogen levels (E1, E2, estriol, and E2/sex hormone-binding globulin)
      were consistently associated (often significantly) with a more unhealthy artery
      wall (thick intima, thin media, and high IMT ratio) in both sexes. Consistently
      strong associations were found between the aromatase index E2/testosterone and
      intima, media, and the IMT ratio. For IMT ratio, in both men (rs = 0.52) and
      women (rs = 0.58), P was <0.001 for both and remained significant after
      adjustment for cardiovascular disease risk factors and the Framingham risk score
      (both P < 0.01). CONCLUSIONS: Low androgens, high aromatase enzyme activity, and
      high estrogen levels are often significantly associated with an unhealthy artery
      wall on ultrasound. We suggest that the steroid hormone profile of older
      individuals with higher estrogens most probably reflects an endogenous response
      to developing atherosclerosis, rather than a cause-and-effect relationship.
      However, the reverse causality cannot be excluded.

PMID- 22990755
TI  - Progression rates of carotid intima-media thickness and adventitial diameter
      during the menopausal transition.
AB  - OBJECTIVE: The aim of this study is to assess whether the levels and progression
      rates of carotid intima-media thickness (IMT) and adventitial diameter (AD) vary
      by menopausal stage. METHODS: Two hundred forty-nine women (aged 42-57 y; 49%
      premenopausal and 46% early perimenopausal) from the Study of Women's Health
      Across the Nation were included in the current analysis. Participants were
      followed up for up to 9 years (median, 3.7 y) and underwent up to five carotid
      scans. Linear mixed-effect models were used for the analysis. RESULTS: The
      overall rate of change in IMT was 0.007 mm/year. Independent of age and race, the
      progression rate of IMT increased substantially in the late perimenopausal stage
      (0.017 mm/y) compared with both the premenopausal stage (0.007 mm/y) and the
      early perimenopausal stage (0.005 mm/y; P <= 0.05). For AD, although the overall
      rate of change was negative (-0.009 mm/y), significant positive increases in the
      rate of change were observed in the late perimenopausal stage (0.024 mm/y) and
      the postmenopausal stage (0.018 mm/y) compared with the premenopausal stage (
      0.032 mm/y; P < 0.05). In the final models, the postmenopausal stage was
      independently associated with higher levels of IMT and AD (P < 0.05) compared
      with the premenopausal stage. CONCLUSIONS: During the menopausal transition, the
      carotid artery undergoes adaptation that is reflected in adverse changes in IMT
      and AD. These changes may have an impact on the vulnerability of the vessel to
      disease in older women.

PMID- 22990756
TI  - Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer.
AB  - OBJECTIVE: The goal of this study was to investigate sexual function in
      postmenopausal breast cancer patients treated with aromatase inhibitors. METHODS:
      A population-based, cross-sectional study was conducted among postmenopausal
      breast cancer patients on adjuvant endocrine treatment and age-matched controls
      with and without estrogen treatment. Sexual function was assessed with a
      standardized questionnaire. RESULTS: In all, 42.4% of aromatase inhibitor-treated
      breast cancer patients were dissatisfied with their sex life in general, and
      50.0% reported low sexual interest; this was significantly more common than in
      tamoxifen-treated patients and controls (P < 0.05). Aromatase inhibitor-treated
      patients reported insufficient lubrication in 73.9% and dyspareunia in 56.5% of
      cases, which were significantly more common than in controls, irrespective of
      hormonal use (P < 0.05). Tamoxifen-treated patients reported significantly more
      dyspareunia (31.3%; P < 0.05) but resembled controls in all other concerns.
      CONCLUSIONS: Our findings suggest that sexual dysfunction in aromatase inhibitor
      treated women is a greatly underestimated problem.

PMID- 22990757
TI  - A randomized, double-blind, multiple-dose escalation study of a Chinese herbal
      medicine preparation (Dang Gui Buxue Tang) for moderate to severe menopausal
      symptoms and quality of life in postmenopausal women.
AB  - OBJECTIVE: This study is a phase II clinical trial that aims to investigate the
      dose-response relationship of a Chinese herbal medicine preparation, Dang Gui
      Buxue Tang (DBT), with short-term menopausal symptoms and quality of life in
      local postmenopausal women. METHODS: A randomized, double-blind, multiple-dose
      escalation trial was performed in 60 postmenopausal women experiencing severe hot
      flashes and night sweats. The participants were randomized to receive DBT
      preparations at 1.5, 3.0, or 6.0 g/day for 12 weeks. The primary outcomes were
      vasomotor symptoms, Greene Climacteric Scale (GCS) score, and Menopause-Specific
      Quality of Life (MENQOL) score. Secondary outcomes included serum hormones and
      lipids. RESULTS: There were between-group differences in
      psychological/psychosocial (P = 0.015, GCS; P = 0.013, MENQOL) and
      somatic/physical (P = 0.019, GCS; P = 0.037, MENQOL) domains, and improvement was
      significantly greatest (P < 0.05) in the 6.0 g/day dose group. The frequency and
      severity of hot flashes and night sweats were significantly reduced in the 3.0
      g/day (14.5%-21.2%, P < 0.05, hot flashes; 28.6%-39.6%, P < 0.05, night sweats)
      and 6.0 g/day (34.9%-37.4.0%, P < 0.01, hot flashes; 10.1%-12.8%, P < 0.01, night
      sweats) dose groups. The female hormones follicle-stimulating hormone,
      luteinizing hormone, and 17beta-estradiol, as well as the lipids total
      cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density
      lipoprotein cholesterol, were not significantly different within groups and
      between groups. CONCLUSIONS: DBT preparations at 6.0 g/day significantly improve
      physical and psychological scores and significantly reduce vasomotor symptoms
      from baseline. The treatment was well tolerated, with no serious adverse events
      noted during the 12-week intervention period. The changes do not affect hormones
      and lipid profiles.

PMID- 22990758
TI  - Paced breathing compared with usual breathing for hot flashes.
AB  - OBJECTIVE: Paced breathing (slow, deep, diaphragmatic breathing) reduces central
      sympathetic activity and facilitates the relaxation response. The present study
      was designed to assess the feasibility of and to obtain initial efficacy
      estimates of two paced-breathing programs, compared with usual breathing, for the
      frequency and severity of hot flashes. METHODS: We designed a 9-week, randomized,
      three-arm, parallel-group, blinded (investigator) phase II clinical trial. Using
      an audio CD, participants in the active arms practiced paced breathing at 6
      breaths/minute for 15 minutes, either once or twice a day, whereas the control
      arm practiced usual breathing at 14 breaths/minute for 10 minutes/day.
      Feasibility was assessed through self-report questionnaires; percent reduction
      and effect size estimates were determined using changes in hot flash frequency
      and scores within each group. RESULTS: Of the 92 eligible participants, 68 (74%)
      completed the study. Most women reported that the intervention was easy to do
      (79%) and of appropriate duration (71%). They could practice exercises as taught
      (61%) and could practice on most days (65%). Participants in all arms reported
      hot flash reductions during the 9 weeks: 52% for paced breathing twice a day, 42%
      for paced breathing once a day, and 46% for usual breathing. CONCLUSIONS: The
      paced-breathing intervention is feasible. Although paced breathing twice a day
      seems to be the most helpful dose, efforts to intensify paced breathing once a
      day may be more practical for widespread dissemination. The efficacy and overall
      clinical impact of paced-breathing exercises on hot flash reduction require
      further evaluation in an adequately powered, placebo-controlled, randomized phase
      III clinical trial.

PMID- 22990759
TI  - Properties of blebbistatin for cardiac optical mapping and other imaging
      applications.
AB  - Blebbistatin is a recently discovered myosin II inhibitor. It is rapidly becoming
      a compound of choice to reduce motion artifacts during cardiac optical mapping,
      as well as to study cell motility and cell invasion. Although blebbistatin has a
      number of advantages over other electromechanical uncouplers, many of its
      properties have yet to be addressed. Here we describe several methodological
      issues associated with the use of blebbistatin, including its spectral
      properties, reversibility, and its effect on tissue metabolic state. We show that
      if precautions are not taken, perfusion with blebbistatin may result in
      blebbistatin precipitate that accumulates in the vasculature. Although such
      precipitate is fluorescent, it is not detectable within wavelength bands that are
      typically used for transmembrane voltage fluorescence imaging (i.e., emission
      wavelengths >600 nm). Therefore, blockage of the microcirculation by blebbistatin
      may cause data misinterpretation in studies that use voltage-sensitive dyes.
      Blebbistatin may also impact imaging of green fluorophores due to the spectral
      shift it causes in endogenous tissue fluorescence. 3D excitation-emission
      matrices of blebbistatin in precipitate form and in various solutions (DMSO,
      water, and 1 % aqueous albumin) revealed significant changes in the fluorescence
      of this molecule in different environments. Finally, we examined the
      reversibility of blebbistatin's uncoupling effect on cardiac contraction. Our
      findings provide important new information about the properties of this myosin II
      inhibitor, which will aid in the proper design and interpretation of studies that
      use this compound.

PMID- 22990761
TI  - Cardiovascular risk in a rural adult West African population: is resting heart
      rate also relevant?
AB  - INTRODUCTION: Elevated resting heart rate (RHR) is a neglected marker in
      cardiovascular risk factor studies of sub-Saharan African populations. This study
      aimed to determine the prevalence of elevated RHR and other risk factors for
      cardiovascular disease (CVD) and to investigate any associations between RHR and
      these risk factors in a rural population in Ghana. DESIGN: Cross-sectional
      analysis. METHODS: A total of 574 adults aged between 18-65 years were randomly
      sampled from a population register. Data collected included those on
      sociodemographic variables and anthropometric, blood pressure (BP), and RHR
      measurements. Within-person variability in RHR was calculated using data from
      repeat measurements taken 2 weeks apart. RESULTS: Of study participants, 36% were
      male. Prevalence of casual high BP was 19%. In the population, 10% were current
      cigarette smokers and habitual alcohol use was high at 56%. As measured by body
      mass index, 2% were obese and 14% had abdominal obesity. RHR was elevated (>90
      bpm) in 19%. Overall, 79% of study participants were found to have at least one
      CVD risk factor. RHR was significantly associated with age, waist circumference,
      and BP. Individuals with an elevated RHR had a higher risk (OR 1.94, 95% CI 1.15
      3.26%, p = 0.013) of casual high BP compared with participants with normal RHR
      independently of several established CVD risk factors. The regression dilution
      ratio of RHR was 0.75 (95% CI 0.62-0.89). CONCLUSIONS: Significant associations
      were observed between RHR and several established cardiovascular risk factors.
      Prospective studies are needed in sub-Saharan African populations to establish
      the potential value of RHR in cardiovascular risk assessment.

PMID- 22990762
TI  - Evaluation of an HIV prevention intervention designed for African American Women:
      results from the SISTA Community-Based Organization Behavioral Outcomes Project.
AB  - One of the Centers for Disease Control and Prevention's strategies for addressing
      racial disparities within the HIV epidemic is to support the implementation of
      HIV prevention behavioral interventions designed for African Americans. One such
      intervention is Sisters Informing Sisters about Topics on AIDS (SISTA), a
      culturally relevant and gender-specific, five-session, group-level, HIV
      prevention intervention designed for African American women. In 2008, the Centers
      for Disease Control and Prevention funded five community-based organizations to
      conduct outcome monitoring of SISTA to assess the outcomes associated with
      implementation in the field. Using a 90-day recall, demographic and sexual risk
      data were collected from participants at baseline and at 90 and 180 days post
      intervention. Findings reveal that women participating in SISTA (n = 432)
      demonstrated a significant reduction in sexual risk between baseline and both
      follow-up time points for each of the six outcomes being measured (e.g., any
      unprotected sex, all protected sex).

PMID- 22990760
TI  - Evolving concepts on regulation and function of renin in distal nephron.
AB  - Sustained stimulation of the intrarenal/intratubular renin-angiotensin system in
      a setting of elevated arterial pressure elicits renal vasoconstriction, increased
      sodium reabsorption, proliferation, fibrosis, and eventual renal injury.
      Activation of luminal AT(1) receptors in proximal and distal nephron segments by
      local Ang II formation stimulates various transport systems. Augmented
      angiotensinogen (AGT) production by proximal tubule cells increases AGT secretion
      contributing to increased proximal Ang II levels and leading to spillover of AGT
      into the distal nephron segments, as reflected by increased urinary AGT
      excretion. The increased distal delivery of AGT provides substrate for renin,
      which is expressed in principal cells of the collecting tubule and collecting
      ducts, and is also stimulated by AT(1) receptor activation. Renin and prorenin
      are secreted into the tubular lumen and act on the AGT delivered from the
      proximal tubule to form more Ang I. The catalytic actions of renin and or
      prorenin may be enhanced by binding to prorenin receptors on the intercalated
      cells or soluble prorenin receptor secreted into the tubular fluid. There is also
      increased luminal angiotensin converting enzyme in collecting ducts facilitating
      Ang II formation leading to stimulation of sodium reabsorption via sodium channel
      and sodium/chloride co-transporter. Thus, increased collecting duct renin
      contributes to Ang II-dependent hypertension by augmenting distal nephron
      intratubular Ang II formation leading to sustained stimulation of sodium
      reabsorption and progression of hypertension.

PMID- 22990764
TI  - Sintering of calcium oxide (CaO) during CO2 chemisorption: a reactive molecular
      dynamics study.
AB  - Reactive dynamics simulations with the reactive force field (ReaxFF) were
      performed in NVE ensembles to study the sintering of two solid calcium oxide
      (CaO) particles with and without CO(2) chemisorption. The simulated sintering
      conditions included starting adsorption temperatures at 1000 K and 1500 K and
      particle separation distances of 0.3 and 0.5 nm. The results revealed that the
      expansion of sorbent particles during CO(2) chemisorption was attributed to the
      sintering of two CaO-CaO particles. Increasing the adsorption temperature
      resulted in more particle expansion and sintering. The shorter the distance
      between two particles, the faster the rate of sintering during CO(2) adsorption.
      A detailed analysis on atom spatial variations revealed that the sorbent
      particles with a larger separation distance had a larger CO(2) uptake because of
      less sintering incurred. The chemisorptions of CO(2) on CaO particles sintered at
      high adsorption temperatures were also simulated to mimic the process of sorbent
      regeneration. It was found that regeneration would be more difficult for sintered
      particles than for fresh particles. In addition, a possible sintering barrier,
      magnesium oxide (MgO), was introduced to prevent CaO particles from sintering
      during CO(2) chemisorption. It was found that the MgO particles could reduce the
      sintering of CaO particles during CO(2) chemisorption. Simulation results from
      this study provided some guidelines on synthesizing or selecting sorbents with
      less sintering effect for multiple CO(2) adsorption-regeneration cycles.

PMID- 22990763
TI  - From coitus to concurrency: sexual partnership characteristics and risk behaviors
      of 15-19 year old men recruited from urban venues in Tanzania.
AB  - Understanding the uptake and patterns of sexual partnerships of adolescent males
      reveals their risky behaviors that could persist into adulthood. Using venue
      based sampling, we surveyed 671 male youth ages 15-19 from an urban Tanzanian
      neighborhood about their sexual partnerships during the past 6 months. The
      proportion of males who had ever had sex increased with age (21 % at age 15; 70 %
      at age 17; 94 % at age 19), as did the proportion who engaged in concurrency (5 %
      at age 15; 28 % at age 17; 44 % at age 19). Attendance at >=2 social venues per
      day and meeting a sexual partner at a venue was associated with concurrency.
      Concurrency was associated with alcohol consumption before sex among 18-19 year
      olds and with not being in school among 15-17 year olds. We find that concurrency
      becomes normative over male adolescence. Venue-based sampling may reach youth
      vulnerable to developing risky sexual partnership patterns. 

PMID- 22990765
TI  - Detecting protein complexes in a PPI network: a gene ontology based multi
      objective evolutionary approach.
AB  - Protein complexes play an important role in cellular mechanism. Identification of
      protein complexes in protein-protein interaction (PPI) networks is the first step
      in understanding the organization and dynamics of cell function. Several high
      throughput experimental techniques produce a large amount of protein
      interactions, which can be used to predict protein complexes in a PPI network. We
      have developed an algorithm PROCOMOSS (Protein Complex Detection using Multi
      objective Evolutionary Approach based on Semantic Similarity) for partitioning
      the whole PPI network into clusters, which serve as predicted protein complexes.
      We consider both graphical properties of a PPI network as well as biological
      properties based on GO semantic similarity measure as objective functions. Here
      three different semantic similarity measures are used for grouping functionally
      similar proteins in the same clusters. We have applied the PROCOMOSS algorithm on
      two different datasets of Saccharomyces cerevisiae to find and predict protein
      complexes. A real-life application of the PROCOMOSS is also shown here by
      applying it in the human PPI network consisting of differentially expressed genes
      affected by gastric cancer. Gene ontology and pathway based analyses are also
      performed to investigate the biological importance of the extracted gene modules.

PMID- 22990766
TI  - Aerosol size distribution and seasonal variation in an urban area of an
      industrial city in central India.
AB  - To study the size distribution and seasonal variations of atmospheric aerosols,
      size-segregated aerosol samples were collected from July 2009 to June 2010 using
      the nine-stage cascade impactor aerosol sampler in Durg City, India. The aerosol
      particles exhibited bimodal size distribution on mass concentration with a peak
      at 2.5-4.4 MUm size ranges in the coarse mode and 2.1-2.5 MUm size ranges in the
      fine mode. The aerosol mass and size distribution during monsoon were found
      unimodal distribution with a peak in the coarse mode, while they showed trimodal
      distributions during winter with all three peaks appearing in the fine mode. The
      annual mean concentration of PM(10) aerosol was found to be 253.5 +/- 99.4
      MUg/m(3), which is four times higher as compared to the annual guideline of
      National Ambient Air Quality Standards (NAAQS) of India prescribed by the Central
      Pollution Control Board (CPCB), India. The highest aerosol mass concentrations
      were found during winter due to enormous biomass burning, while the lowest
      concentrations were observed during monsoon due to heavy rainfall. Air quality
      index values calculated in this study showed that 35% of the days were unhealthy
      for sensitive people, 35% were unhealthy or very unhealthy, while 3.3% were found
      as hazardous in Durg City, India.

PMID- 22990767
TI  - In vitro culturing Plasmodium falciparum erythrocytic stages.
AB  - The in vitro cultivation of Plasmodium falciparum is absolutely essential for the
      molecular dissection of parasite biology and still poses several challenges. The
      dependence on, and interaction with host red blood cells, the tightly regulated
      stage-specific expression of proteins, and the parasite peculiar demands on
      nutrients and gaseous environments are only a few aspects that need to be
      addressed to successfully cultivate P. falciparum in vitro. In this chapter, we
      present techniques for normal maintenance of the erythrocytic stages of P.
      falciparum cultures, their synchronization and the generation of clonal cell
      lines.

PMID- 22990768
TI  - Production of Plasmodium falciparum gametocytes in vitro.
AB  - Production of gametocytes in vitro is essential for studies of Plasmodium
      falciparum sexual stages. Here, we describe procedures for the high-yield
      production and fractionation of P. falciparum gametocytes stages I to V.

PMID- 22990769
TI  - In Vitro Differentiation of Plasmodium falciparum Gametocytes into Ookinetes.
AB  - The ookinete is the motile form of the malaria parasite that invades the mosquito
      midgut epithelium to initiate sporogony. Differentiation of ingested gametocytes
      into ookinetes in the mosquito midgut lumen and the subsequent interaction with
      the luminal surface of the midgut epithelium in preparation for invasion are
      complex processes. To facilitate the study of these events in detail, it is
      necessary to produce sufficient numbers of pure, fully mature ookinetes. However,
      production of even a small number of Plasmodium falciparum ookinetes in vitro has
      proven to be a daunting task. Consequently, over the past four decades our
      collective understanding of the biology of this parasite form remains sorely
      deficient. Here, we describe a new culture technique, which improves the in vitro
      transformation efficiency of P. falciparum gametocytes into mature ookinetes and
      supports the complete development of ookinetes that retain the ability to infect
      the mosquito midgut and to produce oocysts.

PMID- 22990770
TI  - Ex vivo culture of Plasmodium vivax and Plasmodium cynomolgi and in vitro culture
      of Plasmodium knowlesi blood stages.
AB  - Long-term in vitro cultures of blood-stage parasites are so far feasible only for
      Plasmodium falciparum and P. knowlesi. In this chapter, we describe short-term ex
      vivo culturing of P. cynomolgi and P. vivax. We also describe long-term in vitro
      culturing of P. knowlesi as well as some techniques for synchronizing parasites.
      Cultured parasites can be used for a variety of purposes, e.g., for in vitro drug
      assays and antibody-mediated growth inhibition assays.

PMID- 22990771
TI  - Laboratory maintenance of rodent malaria parasites.
AB  - We provide a series of protocols that have been used for the cyclic transmission
      of rodent malaria parasites in the laboratory. This is now possible both in vivo
      and in vitro. We focus on the least "resource intensive" and generic methods that
      we find applicable to any parasite-host combination. Nonetheless, we recognize
      that the ability to construct transgenic "reporter" parasites/hosts now permits
      the use of elegant analytical and imaging technologies both in vitro, ex vivo,
      and in vivo in specific instances. The descriptions given illustrate methods
      routinely used for the maintenance of P. berghei; where critical, we note
      important differences when transmitting other parasite species.

PMID- 22990772
TI  - Transfection of Plasmodium falciparum.
AB  - Genetic manipulation of Plasmodium falciparum remains very challenging, mainly
      due to the parasite genome's high A/T-richness and low transfection efficiency.
      This chapter includes methods for generating transient and stable transfections
      by electroporation, allelic replacement with tagged genes, gene deletion, and the
      analysis of all the above.

PMID- 22990773
TI  - Transfection of rodent malaria parasites.
AB  - Gene manipulation is an invaluable tool to investigate and understand the biology
      of an organism. Although this technology has been applied to both the human and
      rodent malarial parasites (RMP), Plasmodium berghei in particular offers a more
      robust system due to a higher and more efficient transformation rate. Here, we
      describe a comprehensive transfection and selection protocol using P. berghei
      including a variant negative selection protocol administering 5-fluorocytosine to
      the animals in drinking water. Additionally, we discuss and assess the latest
      advances in gene manipulation technologies developed in RMP to gain a better
      understanding of Plasmodium biology.

PMID- 22990774
TI  - Recombination-mediated genetic engineering of Plasmodium berghei DNA.
AB  - DNA of Plasmodium berghei is difficult to manipulate in Escherichia coli by
      conventional restriction and ligation methods due to its high content of adenine
      and thymine (AT) nucleotides. This limits our ability to clone large genes and to
      generate complex vectors for modifying the parasite genome. We here describe a
      protocol for using lambda Red recombinase to modify inserts of a P. berghei
      genomic DNA library constructed in a linear, low-copy, phage-derived vector. The
      method uses primer extensions of 50 bp, which provide sufficient homology for an
      antibiotic resistance marker to recombine efficiently with a P. berghei genomic
      DNA insert in E. coli. In a subsequent in vitro Gateway reaction the bacterial
      marker is replaced with a cassette for selection in P. berghei. The insert is
      then released and used for transfection. The basic techniques we describe here
      can be adapted to generate highly efficient vectors for gene deletion, tagging,
      targeted mutagenesis, or genetic complementation with larger genomic regions.

PMID- 22990775
TI  - Standardization in generating and reporting genetically modified rodent malaria
      parasites: the RMgmDB database.
AB  - Genetically modified Plasmodium parasites are central gene function reagents in
      malaria research. The Rodent Malaria genetically modified DataBase (RMgmDB) (
      www.pberghei.eu ) is a manually curated Web - based repository that contains
      information on genetically modified rodent malaria parasites. It provides easy
      and rapid access to information on the genotype and phenotype of genetically
      modified mutant and reporter parasites. Here, we provide guidelines for
      generating and describing rodent malaria parasite mutants. Standardization in
      describing mutant genotypes and phenotypes is important not only to enhance
      publication quality but also to facilitate cross-linking and mining data from
      multiple sources, and should permit information derived from mutant parasites to
      be used in integrative system biology approaches. We also provide guidelines on
      how to submit information to RMgmDB on non-published mutants, mutants that do not
      exhibit a clear phenotype, as well as negative attempts to disrupt/mutate genes.
      Such information helps to prevent unnecessary duplication of experiments in
      different laboratories, and can provide indirect evidence that these genes are
      essential for blood-stage development.

PMID- 22990776
TI  - Transient transfection of Plasmodium vivax blood-stage parasites.
AB  - Here, we describe the methodology for transient transfection of Plasmodium vivax.
      The ability to genetically manipulate P. vivax has rendered this important human
      malaria parasite more amenable to molecular investigation. However, a systematic
      analysis of this parasite and its disease-mediating interactions with the human
      host still awaits further technological breakthroughs, foremost the establishment
      of a continuous in vitro culture system. Nevertheless, the first steps towards
      domesticating P. vivax for research purposes have been made. Transfection will
      eventually help to better understand the unique pathogenic features displayed by
      P. vivax, such as the host cell specificity for reticulocytes and the occurrence
      of relapses. Transfection will also be an invaluable tool for studies related to
      the emerging drug resistance, and it will help identify and validate novel
      targets for rational intervention.

PMID- 22990777
TI  - Silencing of genes and alleles by RNAi in Anopheles gambiae.
AB  - Anopheles gambiae mosquitoes are the major vectors of human malaria parasites.
      However, mosquitoes are not passive hosts for parasites, actively limiting their
      development in vivo. Our current understanding of the mosquito antiparasitic
      response is mostly based on the phenotypic analysis of gene knockdowns obtained
      by RNA interference (RNAi), through the injection or transfection of long dsRNAs
      in adult mosquitoes or cultured cells, respectively. Recently, RNAi has been
      extended to silence specifically one allele of a given gene in a heterozygous
      context, thus allowing to compare the contribution of different alleles to a
      phenotype in the same genetic background.

PMID- 22990778
TI  - Analysis of variant gene family expression by quantitative PCR.
AB  - Real-time polymerase chain reaction (PCR), or quantitative PCR (qPCR), is a
      rapid, sensitive, and specific method used for a broad variety of applications
      including quantitative gene expression analysis, DNA copy number measurement,
      characterization of gene and chromosomal deletions, and genotyping. Real-time
      reverse transcription (RT)-PCR has largely supplanted Northern blot and RNase
      protection assays, as two examples, as a means of quantifying transcript levels.
      The method utilizes small amounts of RNA and allows efficient screening of a
      large number of samples. Here, we describe the materials and methods required to
      perform real-time RT-PCR, including RNA purification, cDNA synthesis, and real
      time PCR analysis of cDNA samples.

PMID- 22990779
TI  - DNA microarray-based genome-wide analyses of Plasmodium parasites.
AB  - DNA microarray is presently one of the most powerful and fastest growing
      technologies for genomic research of infectious diseases. Accordingly, DNA
      microarray-based global analyses of Plasmodium parasites provided many insights
      into the general biology of malaria infection. From the parasite perspective, it
      was shown that the complex Plasmodium life cycle is characterized by a high level
      of coordination in gene expression but at the same time parasites have a
      considerable capacity to alter their transcriptional profile as a response to
      external stimuli and/or adaptation to varying growth conditions in their host. In
      addition to transcriptional profiling, DNA microarrays were shown to be useful
      for quantitative analyses of Plasmodium genomic DNA including characterizations
      of sequence polymorphisms and copy number variants (CNV) as well as genomic loci
      associated with different chromatin factors (e.g., immunoprecipitated material
      (ChIP-on-chip)). Here, we present protocols for transcriptional profiling,
      comparative genomic hybridization (CGH), and ChIP-on-chip analyses that have been
      developed for the use of low-density long oligonucleotide DNA microarrays of
      Plasmodium species. Many of the presented procedures including RNA purification,
      DNA amplification, and chromatin immunoprecipitation are likely to be
      transferable to other genomic platforms such as other microarray technologies and
      new generation sequencing.

PMID- 22990780
TI  - Whole-genome analysis of Plasmodium spp. Utilizing a new agilent technologies DNA
      microarray platform.
AB  - The application of DNA microarray technologies to malaria genomics has been
      widely used but has been limited by sample availability and technical
      variability. To address these issues, we present a microarray hybridization
      protocol that has been optimized for use with two new Agilent Technologies DNA
      microarrays for Plasmodium falciparum and P. berghei. Using the most recent
      genome sequences available for each species, we have designed ~14,000
      oligonucleotide probes representing ~5,600 transcripts for each species. Included
      in each array design are numerous probes that allow for the identification of
      parasite developmental stages, common Plasmodium molecular markers used in
      genetic manipulation, and manufacturer probes that control for array consistency
      and quality. Overall, the Agilent Plasmodium spp. array designs and hybridization
      methodology provides a sensitive, easy-to-use, high-quality, cost-effective
      alternative to other currently available microarray platforms.

PMID- 22990781
TI  - Transcriptome analysis using RNA-Seq.
AB  - Transcriptome analysis by next-generation sequencing (RNA-seq) allows
      investigation of a transcriptome at unsurpassed resolution. One major benefit is
      that RNA-seq is independent of a priori knowledge on the sequence under
      investigation, thereby also allowing analysis of poorly characterized Plasmodium
      species. Here we provide a detailed protocol for RNA isolation and fragmentation,
      ribosomal RNA depletion, and cDNA synthesis that enables the preparation of a
      sequencing library from 1 to 2 MUg of total RNA. Although we focus our discussion
      on the quantitative measurement of gene expression, this protocol is suited for
      many applications of RNA-seq and allows analysis of most RNA species.

PMID- 22990782
TI  - Experimental tools for the study of protein phosphorylation in Plasmodium.
AB  - The central role played by protein phosphorylation in the regulation of
      eukaryotic cellular processes calls for detailed investigations of this
      phenomenon in malaria parasites. Here, we describe protocols to measure the
      activity of protein kinases (using either recombinant proteins or native enzymes
      purified from parasite extracts), and outline procedures to identify
      phosphorylation sites on parasite proteins following a mass spectrometry
      approach.

PMID- 22990783
TI  - Extraction of hydrophilic metabolites from Plasmodium falciparum-infected
      erythrocytes for metabolomic analysis.
AB  - Metabolomics is an increasingly common analytical approach for investigating
      metabolic networks of pathogenic organisms. This may be of particular use in the
      study of parasitic infections due to the intrinsic metabolic connection between
      the parasite and its host. In vitro cultures of the malaria parasite Plasmodium
      falciparum present a valuable platform to elucidate the structure and dynamics of
      the parasite's metabolic network and to determine the mechanisms of action of
      antimalarial drugs and drug resistance mutations. Accurately measuring metabolite
      levels requires a reproducible method for quantifying intracellular metabolites.
      Here we present a simple protocol for extracting hydrophilic metabolites from P.
      falciparum-infected erythrocyte cultures.

PMID- 22990784
TI  - Static and dynamic imaging of erythrocyte invasion and early intra-erythrocytic
      development in Plasmodium falciparum.
AB  - Cellular imaging has reemerged in recent years as a powerful approach to provide
      researchers with a direct measure of essential molecular events in a cell's life,
      ranging in scale from broad morphological observations of whole cells to
      intricate single molecule imaging. When combined with quantitative image
      analysis, the available imaging techniques can act as a critical means to confirm
      hypotheses, drive the formation of new theories or provide accurate determination
      of protein localization at subcellular and nanometer scales. Here, we describe
      two methodological approaches for imaging the transient step of malaria parasite
      invasion of the human erythrocyte. When applied to image the most virulent human
      malaria parasite, Plasmodium falciparum, the first approach, using live time
      lapse wide-field microscopy, allows the capture of transient events during
      invasion and postinvasion intra-erythrocytic development, while the second, using
      immunofluorescence assay (IFA) of fixed samples, allows high-definition
      exploration of parasite architecture on multiple platforms.

PMID- 22990785
TI  - Flow cytometry-based methods for measurement of cytosolic calcium and surface
      protein expression in Plasmodium falciparum merozoites.
AB  - An increased level of cytosolic free calcium (Ca(2+)) is an essential second
      messenger for apical organelle discharge in Plasmodium falciparum merozoites.
      Here, we describe a method for isolation of viable and invasive P. falciparum
      merozoites. We also describe methods to measure cytosolic Ca(2+) levels in
      merozoites using fluorescent intracellular calcium indicators such as Fluo-4AM by
      flow cytometry. Further, we also describe a flow cytometry-based method to detect
      translocation of apical organelle proteins to the surface of merozoites. Using
      these methods, we have advanced our understanding of signaling pathways involved
      in apical organelle discharge during erythrocyte invasion by P. falciparum
      merozoites.

PMID- 22990786
TI  - Microsphiltration: a microsphere matrix to explore erythrocyte deformability.
AB  - The altered deformability of erythrocytes infected with Plasmodium falciparum is
      central in malaria -pathogenesis, as it influences the hemodynamic properties of
      the infected cell and its retention in the spleen. Exported parasite proteins, as
      well as the shape and volume of the parasite itself, influence the deformability
      of the infected erythrocyte. To explore changes in erythrocyte deformability, we
      have developed a new method, called microsphiltration, based on filtration of
      erythrocytes through a mixture of metal microspheres that mimic the geometry of
      inter-endothelial splenic slits. As P. falciparum develops in its host cell, the
      retention rates observed in microspheres correlate with the progressive decrease
      of erythrocyte deformability and with the retention rates in the spleen. The
      yields of microsphiltration separation allow for molecular analyses of
      subpopulations with distinct mechanical phenotypes.

PMID- 22990787
TI  - Atomic force microscopy of Plasmodium-infected red blood cells: detecting and
      localizing single molecular recognition events.
AB  - Atomic Force Microscopy (AFM) is a powerful tool for exploring the interaction
      between ligands and receptors, as well as their exact locations on the red cell
      surface. Here we discuss current and future applications for AFM based single
      molecule force spectroscopy to study adhesion of Plasmodium-infected red blood
      cells. A protocol is provided for simultaneous topography and recognition imaging
      of the surface of Plasmodium falciparum-infected cells using CD36 functionalized
      tips.

PMID- 22990788
TI  - Expressing full-length functional PfEMP1 proteins in the HEK293 expression
      system.
AB  - Due to the A/T-richness of the genome of Plasmodium falciparum, expressing P.
      falciparum proteins in heterologous expression systems is challenging. In
      addition, many P. falciparum proteins have high cysteine content and high
      molecular weight, which further complicates expression of these proteins in
      heterologous systems. The high molecular weight Plasmodium falciparum Erythrocyte
      Membrane Protein 1 (PfEMP1) adhesins expressed on the surface of the infected
      erythrocytes are among the most difficult proteins to express. Cost reduction in
      synthetic gene synthesis, as well as improved eukaryotic expression systems, now
      makes it possible to express such proteins. In this chapter, we describe the
      construction, production, purification, and functional assessment of the full
      length extracellular region of the var2CSA PfEMP1 protein involved in pregnancy
      associated malaria (PAM), using a human embryonic kidney (HEK) expression system.

PMID- 22990789
TI  - Genome-wide chromatin immunoprecipitation-sequencing in Plasmodium.
AB  - Chromatin immunoprecipitation (ChIP) studies have been used extensively in recent
      years to study the functional role of histone marks, variant histones, and other
      chromatin factors in gene expression in the human malaria parasite, Plasmodium
      falciparum. In this chapter, we present a ChIP-sequencing protocol optimized for
      blood-stage forms of this parasite. The processing of the immunoprecipitated DNA
      prior to high-throughput sequencing is performed in a way to minimize
      amplification biases due to the high genomic AT-content of the parasite.

PMID- 22990790
TI  - In situ fluorescence visualization of transcription sites and genomic Loci in
      blood stages of Plasmodium falciparum.
AB  - Fluorescence-based techniques have been used extensively in the malaria field to
      study the functional role of nuclear organization and gene positioning in blood
      stages of the human malaria parasite, Plasmodium falciparum. In this chapter, we
      present optimized protocols for bromouridine (BrUTP) incorporation into nascent
      RNA in live parasites and fluorescent in situ hybridization (FISH) in fixed
      parasites. Methodology to perform various combinations of the FISH assay, as well
      as a basic approach for quantitative analysis of nuclear position, is also
      described.

PMID- 22990791
TI  - Bioluminescence imaging of P. berghei Schizont sequestration in rodents.
AB  - We describe a technology for imaging the sequestration of infected red blood
      cells (iRBC) of the rodent malaria parasite Plasmodium berghei both in the bodies
      of live mice and in dissected organs, using a transgenic parasite that expresses
      luciferase. Real-time imaging of sequestered iRBC is performed by measuring
      bioluminescence produced by the enzymatic reaction in parasites between the
      luciferase enzyme and its substrate luciferin injected into the mice several
      minutes prior to imaging. The bioluminescence signal is detected by a sensitive I
      CCD photon-counting video camera. Using a reporter parasite that expresses
      luciferase under the control of a schizont-specific promoter (i.e., the ama-1
      promoter), the schizont stage is made visible when detecting bioluminescence
      signals. Schizont sequestration is imaged during short-term infections with
      parasites that are synchronized in development or during ongoing infections. Real
      time in vivo imaging of iRBC will provide increased insights into the dynamics of
      sequestration and its role in pathology, and can be used to evaluate strategies
      that prevent sequestration.

PMID- 22990792
TI  - Scoring sporozoite motility.
AB  - Sporozoites, the stage of Plasmodium infectious to vertebrates when injected in
      the skin by a mosquito vector, are highly motile cells. Their unusual form of
      gliding motility is essential for infectivity, allowing the parasite to travel
      through both the mosquito and mammalian hosts, invading different cell types and
      escaping immune cell-mediated death. In this chapter, we describe techniques to
      study gliding motility of sporozoites in vitro and in vivo.

PMID- 22990793
TI  - Quantification of sporozoite invasion, migration, and development by microscopy
      and flow cytometry.
AB  - There is an important role for in vitro assays to better understand the initial
      steps of malaria infection. In this section, we describe both microscopy-based
      and flow cytometry-based sporozoite invasion, migration and development assays
      with the rodent malaria parasites, Plasmodium berghei and Plasmodium yoelii, and
      the human malaria parasite, Plasmodium falciparum.

PMID- 22990794
TI  - Imaging sporozoite cell traversal in the liver of mice.
AB  - Intravital fluorescence microscopy is an invaluable tool to study a dynamic
      phenomenon through its direct observation in living organisms. This technique can
      combine qualitative and quantitative analysis and has been capital to address
      long-standing questions about Plasmodium biology. Beyond a descriptive view of
      the parasite life cycle, the possibility to image infection in transgenic animals
      in which a specific cell type, molecule or process is labeled opens new
      possibilities to study host cell-parasite interactions in cellular and molecular
      details. An additional layer of refinement can be achieved with the use of
      fluorescent knockout mutants (parasite, mice, or both) to dissect the molecular
      basis of the process of interest. Here, we present a basic protocol for imaging
      the sporozoite behavior in the liver, emphasizing the detection of the
      sporozoite's ability to traverse host cells.

PMID- 22990795
TI  - Analysis of liver stage development in and merozoite release from hepatocytes.
AB  - Exoerythrocytic Plasmodium parasites infect hepatocytes and develop to huge
      multinucleated schizonts inside a parasitophorous vacuole. Finally, thousands of
      merozoites are formed and released into the host cell cytoplasm by complete
      disintegration of the parasitophorous vacuole membrane. This, in turn, results in
      death and detachment of the infected hepatocyte, followed by the formation of
      merosomes. The fast growth of the parasite and host cell detachment are hallmarks
      of liver stage development and can easily be monitored. Here, we describe how to
      translate these observations into assays for characterizing parasite development.
      Additionally, other recently introduced techniques and tools to analyze and
      manipulate liver stage parasites are also discussed.

PMID- 22990796
TI  - Quantitative analysis of Plasmodium berghei liver stages by bioluminescence
      imaging.
AB  - We describe simple and sensitive in vitro and in vivo assays to analyze
      Plasmodium liver stage development using transgenic P. berghei parasites (PbGFP
      Luccon), which express the bioluminescent reporter protein, luciferase. In these
      assays, parasite development in hepatocytes is visualized and quantified by real
      time bioluminescence imaging both in culture and in live mice. We also describe
      quantification of in vitro liver-stage development by measuring luminescence
      using a microplate reader. Reporter-parasite based quantification of liver-stage
      development is faster and correlates very well with established quantitative RT
      PCR methods currently used to assess parasite development inside hepatocytes,
      both in live mice and in culture.

PMID- 22990797
TI  - Activation of human NK cells by Plasmodium-infected red blood cells.
AB  - This chapter describes a protocol to assess activation of human NK cells
      following in vitro stimulation with malaria-infected red blood cells. Activation
      is assessed by flow cytometry, staining for cell surface expression of CD69 and
      accumulation of intracellular IFN-gamma. Procedures are described for in vitro
      propagation and purification of Plasmodium falciparum parasites, separation of
      peripheral blood mononuclear cells from heparinized blood by density
      centrifugation, in vitro culture of PBMC and for staining and analysis of PBMC by
      flow cytometry. Some examples of typical FACS plots are shown.

PMID- 22990798
TI  - Chimeric parasites as tools to study Plasmodium immunology and assess malaria
      vaccines.
AB  - The study of pathogen immunity relies upon being able to track antigen specific
      immune responses and assess their protective capacity. To study immunity to
      Plasmodium antigens, chimeric rodent or human malaria parasites that express
      proteins from other Plasmodium species or unrelated species have been developed.
      Different types of chimeric parasites have been used to address a range of
      specific questions. Parasites expressing model T cell epitopes have been used to
      monitor cellular immune responses to the preerythrocytic and blood stages of
      malaria. Other parasites have been used to assess the functional significance of
      immune responses targeting particular proteins. Finally, a number of rodent
      malaria parasites that express vaccine-candidate antigens from P. falciparum and
      P. vivax have been used in functional assays of vaccine-induced antibody
      responses. Here, I review the experimental contributions that have been made
      using these parasites, and discuss the potential of these approaches to continue
      advancing our understanding of malaria immunology and vaccine research.

PMID- 22990799
TI  - Development and use of TCR transgenic mice for malaria immunology research.
AB  - T-cell receptor transgenic mice are powerful tools to study T cell responses to
      malaria parasites. They allow for a population of antigen specific T cells to be
      monitored during developing responses to immunization or parasite infection; this
      makes them particularly useful to study fundamental aspects of T cell activation,
      differentiation, and migration in different tissue compartments. Moreover, the
      use of these cells allows for a thorough analysis of the mechanisms of
      antiparasite activity by T cells.

PMID- 22990800
TI  - Tracking the total CD8 T cell response following whole Plasmodium vaccination.
AB  - CD8 T cells are critical mediators of protection against Plasmodium liver-stage
      infection. Most studies of the CD8 T cell response to whole parasite Plasmodium
      vaccines address a single T cell epitope in BALB/c mice, and thus provide limited
      information. Here, we describe a surrogate activation marker approach that uses
      the coordinate downregulation of the CD8alpha chain and upregulation of the
      integrin CD11a to track the total CD8 T cell response to Plasmodium vaccination
      via flow cytometry. With this approach, quantitative (magnitude, kinetics) and
      qualitative (distribution, phenotype, and function) features of the total CD8 T
      cell response to vaccination with attenuated Plasmodium or other pathogens can be
      studied.

PMID- 22990801
TI  - Screening inhibitors of P. berghei blood stages using bioluminescent reporter
      parasites.
AB  - We describe two improved assays for in vitro and in vivo screening of inhibitors
      and chemicals for antimalarial activity against blood stages of the rodent
      malaria parasite, Plasmodium berghei. These assays are based on the determination
      of bioluminescence in small blood samples that is produced by reporter parasites
      expressing luciferase. Luciferase production increases as the parasite develops
      in a red blood cell and as the numbers of parasites increase during an infection.
      In the first assay, in vitro drug luminescence (ITDL) assay, the in vitro
      development of ring-stage parasites into mature schizonts in the presence and
      absence of candidate inhibitor(s) is quantified by measuring luciferase activity
      after the parasites have been allowed to mature into schizonts in culture. In the
      second assay, the in vivo drug luminescence (IVDL) assay, in vivo parasite growth
      (using a standard 4-day suppressive drug test) is quantified by measuring the
      luciferase activity of circulating parasites in samples of tail blood of drug
      treated mice.

PMID- 22990802
TI  - Screening and evaluation of inhibitors of Plasmodium falciparum merozoite egress
      and invasion using cytometry.
AB  - Drug discovery programs heavily rely on assays adequately monitoring the activity
      of the drug on the -parasite stage targeted. So far, assays used to screen
      molecules active against Plasmodium falciparum parasites have mostly been based
      on measuring growth inhibition of asexual blood stages. We have developed a
      robust protocol allowing for monitoring parasite egress at the late schizont
      stage and subsequent erythrocyte invasion. This cytometry-based methodology uses
      nucleic acid labelling by the dye YOYO-1 and synchronized in vitro culture of
      P.falciparum exposed to inhibitors during the late phase of the intraerythrocytic
      cycle and the reinvasion process. This cytometry-based method is quick, accurate
      and allows for distinguishing egress from reinvasion on thousands of events. The
      throughput is also increased, as the assay can be scaled up for medium throughput
      screening for compounds that inhibit either the egress of merozoites or their
      entry into host erythrocytes.

PMID- 22990803
TI  - Induction of anti-Plasmodium immunity following subpatent infection with live
      erythrocytic stages and drug cure.
AB  - An effective malaria vaccine remains an important priority for the millions of
      people living in malaria endemic regions. Subambitious goals for the development
      of a vaccine have been set, which aim to achieve a licensed first-generation P.
      falciparum malaria vaccine with more than 50% protective efficacy against severe
      disease and death, lasting for at least 1 year by 2015. These goals were set in
      the context of a subunit vaccine. However, a whole-parasite vaccine might be
      expected to induce substantially superior protection. Our group has been focusing
      on low dose blood-stage parasites as a valid vaccine approach, and we present
      here the relevant methodology for this.

PMID- 22990804
TI  - Vaccination using radiation- or genetically attenuated live sporozoites.
AB  - The attenuation of Plasmodium parasites by either radiation or targeted gene
      deletion can result in viable sporozoites that invade the liver and subsequently
      arrest. The death of the growth-arrested liver stage parasite and the ensuing
      recognition by the immune system of parasite antigens promotes protective
      immunity in immunized mice and humans. The methods described below will enable
      researchers to determine the efficacy of radiation-attenuated and genetically
      attenuated rodent malaria sporozoite immunizations against infectious sporozoite
      challenge, and study protective immunity in immunized mice. In addition, by
      determining the time of arrest of genetically attenuated parasite liver stages
      and the mechanisms of clearance, researchers will be able to correlate biological
      features of the growth-arrested parasites with their ability to promote
      protective immunity.

PMID- 22990805
TI  - Vaccination using normal live sporozoites under drug treatment.
AB  - Sterile immunity against malaria has been obtained in mammalian hosts exclusively
      through vaccination with whole parasite preparations. Induction of complete
      protection against challenge was obtained using sporozoites attenuated by
      irradiation or genetic manipulations. It has been demonstrated recently that
      immunization with normal sporozoites under chloroquine cover confers sterile
      protection in mice and humans, using substantially fewer parasites and injections
      than with irradiated sporozoite immunization. Subsequently, it was shown that
      other drugs can substitute for chloroquine. We describe the immunization protocol
      using live sporozoites under chloroquine cover, which confers sterile immunity in
      rodents.

PMID- 22990806
TI  - Assessing transmission blockade in Plasmodium spp.
AB  - Here we describe a series of methods that can be used to assess the activities of
      "vaccines," drugs, and genetically modified vectors, for their abilities to
      inhibit transmission of Plasmodium from its vertebrate to its mosquito hosts. The
      selection of method to be used is determined by the purpose of the experiment,
      which can include the determination of the site/time of activity, and/or the
      potential reduction in transmission achieved.

PMID- 22990807
TI  - Mosquito transgenic technologies to reduce Plasmodium transmission.
AB  - The ability to introduce genetic constructs of choice into the genome of
      Anopheles mosquitoes provides a valuable tool to study the molecular interactions
      between the Plasmodium parasite and its insect host. In the long term, this
      technology could potentially offer new ways to control vector-borne diseases
      through the suppression of target mosquito populations or through the
      introgression of traits that preclude pathogen transmission. Here, we describe in
      detail protocols for the generation of transgenic Anopheles gambiae mosquitoes
      based on germ-line transformation using either modified transposable elements or
      the site-specific PhiC31 recombinase.

PMID- 22990810
TI  - Parasites of the mangrove mussel Mytella guyanensis (Bivalvia: Mytilidae) in
      Camamu Bay, Bahia, Brazil.
AB  - This contribution reports the parasites found in the mangrove mussel Mytella
      guyanensis in Camamu Bay, Bahia, Brazil. Samples were collected monthly from
      September 2006 through October 2007. A total of 460 individuals were collected,
      fixed in Davidson's solution, and processed by standard histological techniques,
      and the sections were stained with Harris hematoxylin and eosin (H&E). The water
      temperature ranged from 23.5 to 31.6 oC, and the salinity from 25 to 37?.
      Microscopic analysis showed Rickettsia-like organisms (RLOs), Nematopsis sp.
      (Apicomplexa), and Platyhelminthes, including a turbellarian, sporocysts of
      Bucephalus sp., metacercariae, and metacestodes of Tylocephalum sp. Parasites
      were observed mainly in the gills, mantle, and digestive gland. The prevalence of
      Nematopsis sp. was 100%, and in heavily infected mussels the tissues of the
      labial palps were damaged. RLOs occurred in high prevalence and intensity of
      infection in some periods. The digenean sporocysts showed moderate prevalence but
      high intensity of infection, and caused parasitic castration. In general, there
      was no significant spatial or temporal variation (p > 0.05) of the parasites,
      which is probably attributable to the small variations of temperature and
      salinity in the region.

PMID- 22990808
TI  - Modeling of Functional Assessment Questionnaire (FAQ) as continuous bounded data
      from the ADNI database.
AB  - An assessment of abilities to function independently in daily life is an
      important clinical endpoint for all Alzheimer's disease (AD) patients and
      caregivers. A mathematical model was developed to describe the natural history of
      change of the Functional Assessment Questionnaire (FAQ) from data obtained in
      normal elderly, mild cognitive impairment, and mild AD in the AD neuroimaging
      initiative (ADNI) study. FAQ is a bounded outcome (ranging from 0 to 30), with 0
      scored as "no impairment" and 30 as "severely impaired". Since many normal
      elderly patients had 0 scores and some AD patients had scores of 30 in the ADNI
      database, a censored approach for handling the boundary data was compared with a
      standard approach, which ignores the bounded nature of the data. Baseline
      severity, ApoE4 genotype, age, sex, and imaging biomarkers were tested as
      covariates. The censored approach greatly improved the predictability of the
      disease progression in FAQ scores. The basic method for handling boundary data
      used in this analysis is also applicable to handle boundary observations for
      numerous other endpoints.

PMID- 22990809
TI  - Ca(V)1.2 I-II linker structure and Timothy syndrome.
AB  - Ca(V) channels are multi-subunit protein complexes that enable inward cellular
      Ca(2+) currents in response to membrane depolarization. We recently described
      structure-function studies of the intracellular alpha1 subunit domain I-II
      linker, directly downstream of domain IS6. The results show the extent of the
      linker's helical structure to be subfamily dependent, as dictated by highly
      conserved primary sequence differences. Moreover, the difference in structure
      confers different biophysical properties, particularly the extent and kinetics of
      voltage and calcium-dependent inactivation. Timothy syndrome is a human genetic
      disorder due to mutations in the Ca(V)1.2 gene. Here, we explored whether
      perturbation of the I-II linker helical structure might provide a mechanistic
      explanation for a Timothy syndrome mutant's (human Ca(V)1.2 G406R equivalent)
      biophysical effects on inactivation and activation. The results are equivocal,
      suggesting that a full mechanistic explanation for this Timothy syndrome mutation
      requires further investigation.

PMID- 22990811
TI  - Effect of sediment composition on methane concentration and production in the
      transition zone of a mangrove (Sepetiba Bay, Rio de Janeiro, Brazil).
AB  - The aim of this research was to evaluate the effect of sediment composition on
      methane (CH4) dynamics in sediments of different areas in the transition zone
      between a mangrove and the sea. This research was conducted in a mangrove at
      Coroa Grande, on the southern coast of Rio de Janeiro. Samples were collected at
      three stations: (1) region colonised by Rhizophora mangle L. on the edge of the
      mangrove, (2) region colonised by seagrasses and (3) infra-littoral region
      without vegetation. Samples were collected from the surface layer of the sediment
      to determine the concentrations of nutrients (C, N and P) and CH4 concentration
      and production. We observed that concentrations of CH4 and carbon (C) were
      significantly higher (p < 0.05) in station 1 than station 3. The molar ratios
      (C:N, C:P and N:P) suggest that the origin of the substrate is mainly
      autochthonous. Methanogenesis was initially low, possibly due to competition
      between methanogens and sulfate reducers, and increased significantly (p < 0.05)
      on the twenty-sixth day in the sediment of station 1, probably due to higher
      organic matter (OM) availability in this region. Results indicate that
      methanogenic activity observed herein is not regulated by the amount or quality
      of OM, but by other factors. The concentration of CH4 in the sea-land ecotone at
      Mangrove Coroa Grande is a function of available OM suggesting a possible
      inhibition of methanotrophy by intense oxygen consumption in the soil surface
      covered by detritus of Rhizophora mangle vegetation.

PMID- 22990812
TI  - Influence of agricultural land-use and pesticides on benthic macroinvertebrate
      assemblages in an agricultural river basin in southeast Brazil.
AB  - Land-use alterations and pesticide run-offs are among the main causes for
      impairment in agricultural areas. We evaluated the influence of different land
      uses (forest, pasture and intensive agriculture) on the water quality and on
      benthic macroinvertebrate assemblages on three occasions: in the dry season, wet
      season and at the end of the wet season. Macroinvertebrates responded to this
      gradient of impairment: agricultural sites had significantly lower richness
      numbers than forested and pasture sites, and all major invertebrate groups were
      significantly affected. Most taxa found in forested sites were found in pasture
      sites, but often with lower densities. In this case, the loss of habitats due to
      sedimentation and the lower complexity of substrates seem to be the disruptive
      force for the macroinvertebrate fauna.

PMID- 22990813
TI  - Modelling the population control of the domestic cat: an example from an island
      in Brazil.
AB  - The domestic cat is an invasive species that often causes great impacts where
      introduced due to its high predatory and reproductive potential, especially on
      islands. In this study, carried out on Ilha Grande (RJ, Brazil), we aimed to: i)
      estimate the population density of domestic cats, ii) calculate the number of
      animals preyed upon annually by domestic cats, and iii) evaluate the efficiency
      of methods to control the cat population. We used the Vortex program to project
      the population growth of domestic cats in fifty years, and simulated different
      scenarios of population control (without control, castration, spay and harvest).
      Population density of owned cats was 662 cats/km2. The annual predation rate was
      1.97 prey animals/cat which is an average of 1497.96 prey/year. The population
      would only be reduced if 70% of females were spayed or removed annually. Measures
      to control the domestic cat population must be undertaken urgently, since
      uncontrolled growth of this predator has the potential to seriously impact the
      biodiversity of Ilha Grande.

PMID- 22990814
TI  - Herbivory among habitats on the Neotropical tree Cnidoscolus quercifolius Pohl.
      in a seasonally deciduous forest.
AB  - Our goal was to identify herbivory patterns from two insect guilds associated
      with Cnidoscolus quercifolius in a tropical deciduous forest in northeastern
      Brazil. We sampled four different habitats: (1) forest edge, (2) mesic (near to
      the perennial water source), (3) forest interior and (4) rupestrian fields.
      Habitat edge had lower leaf damage than rupestrian, mesic and forest interior
      habitats. Nevertheless, abundance of galls at the edge habitat was higher than at
      mesic, forest interior and/or rupestrian habitats. There was no difference in
      gall mortality by natural enemies among the four habitats sampled, demonstrating
      the absence of any influence of top-down controls related to abundance of galls.
      Trophic relationships were not related to the patterns of distribution among
      habitats of two insect herbivorous guilds associated with C. quercifolius. Our
      results demonstrated that environmental heterogeneity of dry forests can
      significantly alter important ecological interactions and experimental studies
      are needed to better understand the mechanisms responsible for differences in
      herbivory among habitats.

PMID- 22990815
TI  - Foraging of Great Kiskadees (Pitangus sulphuratus) and food items offered to
      nestlings in the Pantanal.
AB  - Feeding of Pitangus sulphuratus (Tyrannidae) nestlings have been poorly studied.
      Here we describe the foraging behavior of a P. sulphuratus pair and the searching
      and offering time of food items to nestlings in the Pantanal, Brazil. Data
      collection was carried out over 25 days on the outskirts of the Base de Estudos
      do Pantanal building, inhabited by insectivorous bats. Records were based on
      direct observations with the help of binocular. The pair required little time for
      searching for small insects and fruits, but these items comprised a little amount
      of food per event of capture. Some large prey was more time-costly for searching,
      but the long period that these food items were offered to nestlings
      overcompensated the searching time. Considering the time of feeding nestlings
      (benefit) in relation to the searching time by the parents (cost), bats and
      snails are the most advantageous items for P. sulphuratus parents feeding
      nestlings at the study site.

PMID- 22990816
TI  - Functional diversity, soil features and community functioning: a test in a
      cerrado site.
AB  - Community functioning may be affected by functional diversity, which measures the
      extent of complementarity in resource use. We tested whether there was a
      relationship between functional diversity of woody species and community
      functioning on a fine scale, using FD as a measure of functional diversity and
      litter decomposition rate as a surrogate for community functioning. We measured
      eight functional traits from a woodland cerrado community in southeastern Brazil.
      Then, we tested the correlation between FD and the decomposition rate taking into
      account differences in soil features and between decomposition rate and each
      trait separately. The decomposition rate was related to the aluminium and
      phosphorus concentration in soil, but not to FD, pointing out that functional
      diversity was not a good predictor of community functioning. There was a non
      significant relationship between FD and the decomposition rate even when we
      considered each trait separately. Most studies in the relationships between
      biodiversity and community functioning on fine scales were carried out by
      experimental manipulation of diversity and in temperate regions. We carried out
      this fine scale study as a mensurative experiment and in a tropical savanna. Our
      findings indicated that the relationship between biodiversity and community
      functioning is not as straightforward as usually assumed.

PMID- 22990817
TI  - Genotoxicity and toxicity evaluations of ECF cellulose bleaching effluents using
      the Allium cepa L. test.
AB  - Toxicity and genotoxicity tests were performed on root cells of Allium cepa in
      order to evaluate wastewater quality following an ECF cellulose bleaching
      process. The results revealed a toxic effect of the effluent, with inhibition of
      meristem growth and generally lower values of metaphase, anaphase and telophase
      indices at pH 10.5 than pH 7 for all effluent concentrations. The genotoxicity
      effect was different from the toxic effect given that the micronucleus and the
      chromosomal aberration tests in anaphase-telophase cells were low over all ranges
      of the studied effluent concentrations.

PMID- 22990818
TI  - Fluctuations of the population of Daphnia laevis Birge 1878: a six-year study in
      a tropical lake.
AB  - The fluctuation of the population of Daphnia laevis in Lake Jacare (Middle River
      Doce, Minas Gerais) was monitored monthly (at one point in the limnetic region)
      for six years (2002-2007) as part of the Program of Long-Term Ecological Research
      (LTER/UFMG). The following parameters were also monitored: water temperature, pH,
      electrical conductivity, dissolved oxygen, chlorophyll a, total phosphorus,
      phosphate, total nitrogen, nitrate, nitrite, ammonia, and densities of Chaoborus
      and ephippia of Daphnia laevis in the sediment. A seasonal pattern was observed
      in the fluctuation of D. laevis, with higher densities recorded during periods of
      circulation (May-August). A significant correlation was found between the density
      of D. laevis and temperature (r = -0.47, p = 0.0001), chlorophyll-a (r = -0.32, p
      = 0.016) and indicators of the lake's trophic status (total phosphorus, r = 0.32,
      p = 0.007 and trophic state, r = 0.36, p = 0.003), as well as Chaoborus density
      (r = 0.43 and p = 0.002). These results indicate that changes in the physical and
      chemical characteristics of the water related with stratification and circulation
      of the lake may have a direct (temperature, total phosphorous) or an indirect
      (food availability, presence of predators, ephippia eclosion) influence on the
      fluctuation of the D. laevis population.

PMID- 22990819
TI  - Structure of the littoral fish assemblage in an impounded tributary: the effects
      of macrophytes presence (subtropical region, Brazil).
AB  - To evaluate the effects of macrophytes presence in the structure of littoral fish
      assemblages in the littoral zone, monthly samples were collected from September,
      2006 to August, 2007 in an impounded tributary of the Ita Reservoir, the Fragosos
      River, located in the Upper Uruguay River Basin. Fish were collected using a
      beach seine and sampling was conducted in the littoral zone inside a macrophyte
      stand and in an area with no macrophytes. A total of 5,191 fish were captured
      during the study period. Fish assemblage attributes (fish abundance, species
      richness, and diversity) varied significantly between sampling months and areas.
      The abundance of Astyanax cf. bimaculatus, Astyanax fasciatus, Geophagus
      brasiliensis, and Gymnotus carapo also varied significantly between sampling
      months and areas. Detrended Correspondence Analysis showed a clear spatial
      segregation at the first axis and a slight temporal segregation at the second
      axis. These results were confirmed by Multiple Response Permutation Procedure
      analysis. Apparently, the presence of the aquatic macrophytes is not the only
      factor influencing the distribution of littoral fish assemblages in the Fragosos
      River. Littoral fish seem to be taking advantage of low- to medium-sized
      macrophyte stands, but few species used maximum-sized stands.

PMID- 22990820
TI  - Geographical patterns and partition of turnover and richness components of beta
      diversity in faunas from Tocantins river valley.
AB  - There has been a resurging interest in patterns of beta-diversity, especially by
      the mechanisms driving broad-scale, continental and global patterns, and how
      partitioning beta-diversity into richness (or nestedness) and turnover components
      can be linked with such mechanisms. Here we compared two recent methodologies to
      find richness and turnover components of beta-diversity, using a large regional
      scale dataset of mammal, bird, reptiles and amphibian species found in seven
      regions of Central, North and Northeastern Brazil. As well as a simple comparison
      of the metrics available, we analyzed spatial patterns (i.e., distance-decay
      similarity) and the effects of biome type in these components using raw and
      partial Mantel tests. Our analyses revealed that turnover estimated using
      Baselga's (2010) approach is slightly higher than the estimate using Carvalho's
      et al. (2012) approach, but all analyses show consistent spatial patterns in
      species turnover using both methods. Spatial patterns in beta-diversity revealed
      by Mantel tests are also consistent with expectations based on differential
      dispersal abilities. Our results also reinforce that spatial patterns in beta
      diversity, mainly in the turnover components expressing faunal differentiation,
      are determined by a mix or broad scale environmental effects and short distance
      spatially-structured dispersal.

PMID- 22990821
TI  - Bioactivity evaluation against Artemia salina Leach of medicinal plants used in
      Brazilian Northeastern folk medicine.
AB  - The brine shrimp (Artemia salina Leach) lethality bioassay offers an advantage in
      standardization and quality control of botanical products. This test is well
      correlated with antitumor activity (cytotoxicity) and can be used to monitor the
      activity of bioactive natural products. This paper reports the bioactivity of
      ethanol extracts from seven medicinal plants from the Northeast of Brazil
      (Acmella uliginosa, Ageratum conyzoides, Eugenia uniflora, Plectranthus
      neochilus, Moringa oleifera, Justicia pectoralis and Equisetum sp.) against
      Artemia salina. Biological activity was evaluated for extracts at 1, 10, 100, and
      1000 ug/mL in triplicate, and the mean lethal concentration values (LC50) were
      obtained by probit analysis. The species Acmella uliginosa showed the highest
      bioactivity, and its flower extract was more active than its leaf extract.

PMID- 22990822
TI  - Sensitivity of populations of bats (Mammalia: Chiroptera) in relation to human
      development in northern Parana, southern Brazil.
AB  - Most natural forests have been converted for human use, restricting biological
      life to small forest fragments. Many animals, including some species of bats are
      disappearing and the list of these species grows every day. It seems that the
      destruction of the habitat is one of its major causes. This study aimed to
      analyze how this community of bats was made up in environments with different
      sizes and quality of habitat. Data from studies conducted in the region of
      Londrina, Parana, Brazil, from 1982 to 2000 were used. Originally, this area was
      covered by a semi deciduous forest, especially Aspidosperma polyneuron
      (Apocynaceae), Ficus insipida (Moraceae), Euterpe edulis (Arecaceae), Croton
      floribundus (Euforbiaceae), and currently, only small remnants of the original
      vegetation still exist. The results showed a decline in the number of species
      caught in smaller areas compared to the largest remnant. In about 18 years of
      sampling, 42 species of bats were found in the region, representing 67% of the
      species that occur in Parana and 24.4% in Brazil. There were two species of
      Noctilionidae; 21 of Phyllostoma; 11 Vespertilionidae and eight Molossidae. Eight
      of these were captured only in the largest fragment, Mata dos Godoy State Park
      (680 ha). Ten species had a low capture rate in the smaller areas with less than
      three individuals. Of the total sampled, 14 species were found in human
      buildings, and were able to tolerate modified environments, foraging and even
      using them as shelter. As the size of the forest area increases, there is a
      greater variety of ecological opportunities and their physical conditions become
      more stable, i.e., conditions favorable for growth and survival of a greater
      number of species. Forest fragmentation limits and creates subpopulations,
      preserving only long-lived K-strategist animals for some time, where the
      supporting capacity of the environment is a limiting factor. The reduction of
      habitats, species and genetic diversity resulting from human activities are
      endangering the future adaptability in natural ecosystems, which promotes the
      disappearance of low adaptive potential species.

PMID- 22990823
TI  - Structure of aquatic vegetation of a large lake, western border of the Brazilian
      Pantanal.
AB  - Studies on Neotropical aquatic macrophytes have increased in recent decades,
      however species richness in wetlands of South America is far from being fully
      known. In addition, studies having an ecological approach are scarce in the
      Pantanal. Rapid assessments are essential for gaining knowledge of the
      biodiversity in the region. This study was performed in five sites of the Baia do
      Castelo, the western border of the Brazilian Pantanal, which included wild-rice
      patches, floating mats and floating meadows. At each site, plots of 0.5 * 0.5 m
      were set (n = 137), species of aquatic macrophytes were identified, their
      coverage was measured and the plot depth was estimated. We recorded 57 species in
      26 families, of which Poaceae was the richest. The most frequent and abundant
      species was Commelina schomburgkiana; the second most frequent was Oryza
      latifolia,followed by Leersia hexandra, Enydra radicans and Pityrogramma
      calomelanos. The latter species was second in cover, followed by Pontederia
      rotundifolia, Eichhornia azurea, E. crassipes and Enydra radicans. These five
      species and C. schomburgkiana (the most abundant) together represent more than
      half of the coverage on the lake. Pontederia rotundifolia, Ludwigia
      helminthorrhiza, Pistia stratiotes, E. azurea, E. crassipes, Enydra radicans and
      Panicum elephantipes were strongly associated with deeper areas, while Oryza
      latifolia, Leersia hexandra and Salvinia auriculata were prevalent in shallow
      areas. Pityrogramma calomelanos, Ludwigia nervosa, Ipomoea alba, Cayaponia
      podantha, Polygonum acuminatum, Rhynchanthera novemnervia and Ludwigia leptocarpa
      were highly correlated with floating meadows. The structure of the habitat,
      natural dynamics and zonation of aquatic vegetation in the Baia do Castelo seems
      to be influenced by a variation in water levels, which promotes spatial
      segregation, most likely due to competition and/habitat preference.

PMID- 22990824
TI  - Seasonal dynamics of cyanobacteria in a eutrophic reservoir (Arcoverde) in a semi
      arid region of Brazil.
AB  - Environmental conditions favor the predominance of dense populations of
      cyanobacteria in reservoirs in northeastern Brazil. The aim of this study was to
      understand cyanobacterial population dynamics in the rainy and dry seasons at two
      depths in the Arcoverde reservoir. Microalgae and cyanobacteria samples were
      collected during 24 hours with intervals of 4 hours (nycthemeral) at sub-surface
      and 10 m using a van Dorn bottle and a determined biomass. Physical and chemical
      variables were obtained and the data were analyzed using the principal component
      analysis (PCA). No nycthemeral variations in the taxonomic composition or
      distribution of the populations of cyanobacteria were found between the different
      times of day in either the rainy or dry season. In both seasons, the greatest
      biomass of the phytoplankton community was made up of cyanobacteria at two depths
      and all times of the day. Cylindrospermopsis raciborskii (Woloszynska) Seenayya
      et Subba Raju was dominant at all times of the day on both the surface and at the
      bottom. In the rainy season, the differences in cyanobacterial biomass between
      the surface and bottom were less significant than in the dry season. The
      differences in cyanobacterial biomass between surface and bottom were less
      pronounced than those found in the dry season. We concluded that a) physical
      variables better explain the alterations of species in the phytoplankton
      community in an environment dominated by cyanobacteria throughout the year; b)
      seasonal climatic factors associated to periods of stratification and de
      stratification are important for alterations in the community and variations in
      biomass and, c) the turbidity caused by rainfall favored the emergence and
      establishment of other cyanobacteria, especially Planktothrix agardhii (Gomont)
      Anagnostidis & Komarek.

PMID- 22990825
TI  - Variations on the larval incubation of Anodontites trapesialis (Unionoida,
      Mycetopodidae): Synergetic effect of the environmental factors and host
      availability.
AB  - The unionid Anodontites trapesilais (Lamarck, 1819) like most freshwater mussels
      is a parasite of fish. So it is trivial to assume that the availability of hosts
      is an important factor for the maintenance of unionoid populations. What seems
      obvious is not always so easy to demonstrate. This study proposes to investigate
      the effects of abiotic and biotic variables related to the incubation of larvae
      in A. trapesialis. For this, we estimate different biological indexes and try to
      capture the dimensionality of the fish, along with the temporal variation of
      environmental variables. From the application of a CCA, it was demonstrated that
      there was a synchronicity among the factors and variables proposed here, and we
      infer that the flood pulse acts as a synergistic factor in this process.

PMID- 22990826
TI  - Herpetofauna of Nucleo Experimental de Iguaba Grande, Rio de Janeiro state,
      Brazil.
AB  - The Atlantic Rain forest, which is considered the second largest pluvial forest
      in the American continent, has had an estimated 93% of its original area
      destroyed. Although studies concerning the herpetofaunal diversity in this biome
      have been intensified in the past years, its diversity is still underestimated.
      The Nucleo Experimental de Iguaba Grande (NEIG) is included in an Environmental
      Protection Area (APA de Sapeatiba) in the Iguaba Grande municipality, Rio de
      Janeiro state, Brazil (22o 51' S and 42o 10' W). The goal of this study was to
      conduct an inventory of the reptile and amphibian species that occur in this area
      between July 2008 and December 2009. We recorded 19 species of amphibians (18
      anurans and one caecilian) and 15 species of reptiles (three lizards, 11 snakes
      and one amphisbaenian). Leptodactylus latrans and L. mystacinus had the highest
      capture rates among amphibians captured, and among reptiles, Ameiva ameiva,
      Hemidactylus mabouia and Mabuya agilis had the highest capture rates. Rarefaction
      curves for both amphibians and reptiles did not reach the asymptote, indicating
      that the species richness in the NEIG is still underestimated.

PMID- 22990827
TI  - Differences in richness and composition of gastrointestinal parasites of small
      rodents (Cricetidae, Rodentia) in a continental and insular area of the Atlantic
      Forest in Santa Catarina state, Brazil.
AB  - The first and only study on gastrointestinal parasites of wild rodents in the
      Island of Santa Catarina was done in 1987. The aim of this study was to identify
      intestinal parasites from wild rodents in Santo Amaro da Imperatriz and Santa
      Catariana Island, and to compare the richness and composition of the
      gastrointestinal parasite community of both areas. Rodents were captured with
      live traps, and feces were screened using the sedimentation method and optical
      microscopy. The following species of rodents were captured in the two areas:
      Akodon montensis, Euryoryzomys russatus, Oligoryzomys nigripes and Nectomys
      squamipes. In Santo Amaro da Impetratriz, prevalent parasites were: A. montensis
      (51%), E. russatus (62%), O. nigripes (53%) and N. squamipes (20%). From the
      Island of Santa Catarina the rodent prevalence rates were: A. montensis (43%), E.
      russatus (59%), O. nigripes (30%) and N. squamipes (33%) and the collected
      parasites were: Hymenolepis sp., Longistriata sp., Strongyloides sp.,
      Hassalstrongylus sp., Syphacia sp., Trichomonas sp., Ancylostomidae, Trichuridae,
      Oxyuridae and Eucoccidiorida. The species richness (10.6 +/- 0.7) of the
      endoparasite comunity in the area located on the continent was higher (p < 0.01)
      and different (p = 0.001) from that of the area located on the island (6.9 +/-
      0.5).

PMID- 22990828
TI  - Reproductive cycle of Tagelus plebeius (Mollusca: Bivalvia) in the estuary of the
      Cachoeira River, Ilheus, Bahia, Brazil.
AB  - This study characterized the reproductive cycle of the stout razor clam Tagelus
      plebeius in the estuary of the Cachoeira River, Ilheus, Bahia, northeastern
      Brazil. Samples of 20 animals per collection were taken biweekly from August 2005
      to August 2006. The 480 specimens were measured on the antero-posterior axis
      (length) and then removed from the shell. After macroscopic analysis, the gonads
      were fixed in Davidson's solution, processed by routine histology and stained by
      Harris hematoxylin and eosin. The gonads of both males and females appeared milky
      white, without sexual dimorphism. Microscopic analyses indicated a M: F ratio of
      1.06: 1 and continuous reproduction of T. plebeius in the region. The period from
      August to October showed the most intense spawning. This study provides another
      example of continuous reproduction of bivalves in tropical waters, and because
      this species is a heavily exploited fishery resource in the region, it draws
      attention to the need for a management plan aimed at reducing harvests.

PMID- 22990829
TI  - Primary embryonic cells of Rhipicephalus microplus and Amblyomma cajennense ticks
      as a substrate for the development of Borrelia burgdorferi (strain G39/40).
AB  - Borrelia burgdorferi, the agent of Lyme borreliosis, is a spirochetes transmitted
      by ticks to humans and animals. Its cultivation in vitro in tick cells allows
      studies of its biology and provides methodology for future research in Brazil,
      and for the isolation of Borrelia spp. We examined in vitro the characteristics
      of embryonic cells of Rhipicephalus microplus and Amblyomma cajennense in cell
      culture and investigated the suitability of embryonic cells as a substrate for
      cultivation of B. burgdorferi. Subcultures were prepared from primary cultures of
      embrionary cells of R. microplus and A. cajennense maintained in Leibovitz's (L
      15) complete medium at 28 oC and 31 oC, respectively. When a monolayer had
      formed, the L-15 was replaced with Barbour-Stoener-Kelly medium for experiments
      to infect cell cultures with B. burgdorferi. After 72 hours of cultivation, the
      spirochetes were counted using an inverted phase contrast microscope and dark
      field illumination (400*). Survival, multiplication and the adherence of B.
      burgdorferi for embryonic cells of R. microplus and A. cajennense were observed.
      B. burgdorferi cultured with embryonic cells of R. microplus grew on average to a
      density (final count) of 2.4 * 10(7) spirochetes/mL, whereas in cell-free
      culture, an average of 2.5 * 10(7) spirochetes/mL were counted. When cultivated
      with A. cajennense cells, the final count of spirochetes was on average 1.7 *
      10(7) spirochetes/mL, while spirochetes cultured under cell-free conditions
      replicated on average of 2.2 * 10(7) spirochetes/mL. Similar results were
      observed in the final count of Spirochetes cultivated in cells of R. microplus
      and A. cajennense, when compared with cell-free control. These results
      demonstrated that cells of R. microplus and A. cajennense have the potential to
      be used as growth substrate for B. burgdorferi in the study of its interaction
      with host cells.

PMID- 22990830
TI  - Phthiraptera and Gamasida parasites of Columbina picui (Temminck) (Columbiformes:
      Columbidae) in the State of Rio Grande do Sul, Southern Brazil.
AB  - Thirty-two specimens of Columbina picui (picui ground-dove) were examined, and a
      collection of arthropods was made by washing the external surface of the body and
      the nasal cavity. The species in the order Phthiraptera found and their
      respective prevalences, mean abundance and mean intensity were: Columbicola
      passerinae (84.4%; 10.3; 12.2), Hohorstiella passerinae (21.9%; 0.7; 3.1) and
      Physconelloides eurysema (3.1%; 0.1; 2). The gamasid mites found in the birds and
      their respective prevalences, mean abundance and mean intensity were: Pellonyssus
      marui (31.3%; 1.2; 3.9), Ornithonyssus bursa (15.6%; 0.2. ;1.2) and Mesonyssus
      sp. (6.3%; 0.1; 1). Columbicola passerinae, H. passerinae, P. eurysema, O. bursa,
      P. marui and Mesonyssus sp. were recorded for the first time infecting C. picui
      in Brazil. Except for O. bursa, the other species are reported for the first time
      in the state of Rio Grande do Sul, Brazil.

PMID- 22990831
TI  - Edge effect and phenology in Erythroxylum tortuosum (Erythroxylaceae), a typical
      plant of the Brazilian Cerrado.
AB  - The edge of a forest fragment can be considered a zone of transition between the
      interior of the fragment and the surrounding habitat matrix. Plants along the
      edge are more exposed to disturbance and microclimate variation than interior
      plants, resulting in the so-called edge effect. In this study, we compared leaf
      area, fluctuating asymmetry and chemical (water, nitrogen and tannins) leaf
      traits between Erythroxylum tortuosum plants inhabiting the edge with those
      growing in the interior of a cerrado fragment in Brazil. We also describe the
      temporal variation in the vegetative and reproductive phenological events of E.
      tortuosum plants throughout the season. Nitrogen, leaf area and fluctuating
      asymmetry did not differ between the two plant groups. Young leaves of the edge
      plants had significantly higher levels of tannins and lower levels of water than
      those of interior plants. We suggest that differences in leaf chemical
      concentrations between edge and interior plants may occur due to factors such as
      light intensity, wind, temperature and leaf age rather than plant stress. With
      respect to plant phenology, most reproductive events occurred during the spring.
      Leaf buds and young leaves prevailed during the rainy season. In the dry season,
      however, the vegetative events decreased due to leaf senescence followed by leaf
      abscission.

PMID- 22990832
TI  - Morphometric variations of laelapine mite (Acari: Mesostigmata) populations
      infesting small mammals (Mammalia) in Brazil.
AB  - The goal of this study was to evaluate the morphometric variation of laelapine
      populations (Acari, Mesostigmata) associated with neotropical oryzomyine rodents
      at different geographic localities in Brazil. Three nominal mite species were
      selected for study, all infesting the pelage of small mammals at different
      localities in Rio de Janeiro, Espirito Santo, Bahia, and the Federal District,
      Brazil. To analyse morphometric characteristics, thirty-seven morphological
      characters distributed across the whole body of each specimen were measured. We
      use the Analysis of Principal Components, extracting the three first axes and
      projecting each mite in these axes. Major species level changes in the taxonomy
      of the host mammals allows an independent examination of morphometric variation
      of mites infesting a set of distinctly different host species at different
      geographic localities. Gigantolaelaps vitzthumi and Laelaps differens are
      associated with oryzomyine rodents of the genus Cerradomys, and consistently
      showed a tendency to cluster by host phylogeny. Laelaps manguinhosi associated
      with Nectomys rattus in central Brazil is morphometrically distinct from mites
      infesting N. squamipes in the coastal restingas of Rio de Janeiro and Espirito
      Santo. The results obtained here indicate that laelapine mite populations can
      vary among geographic areas and among phylogenetically related host species.
      Clearly, the study of these mites at the population level can be an important
      tool for clarifying the taxonomy of both mites and hosts.

PMID- 22990833
TI  - Metapopulation in bats of Southern Brazil.
AB  - The purpose was to show that displacements, promoters of genetic diversity in
      metapopulations, increase the probability of survival of bat species adapted to
      medium and long-distance flights. Samples were taken in four forest fragments,
      distributed in three municipalities in northern Parana, and the maximum distance
      between the studied areas is 20 km. A monthly sampling was performed for each
      fragment, for the period of July 2008 to June 2009. We used eight nets for
      collection which remained open during the first four hours of the night,
      totalling 192 hours during a year of study. The marking occurred from October
      2008 to March 2009 and was accomplished through the use of anodised metal rings
      of four different colours. One hundred and fifty individuals were banded and
      since the first capture, four displacements were recorded. After five months of
      collecting and marking, one Carollia perspicillata was found three km away. Two
      Artibeus lituratus were recorded about 20 km from the marking place: the first
      one after 22 months and the second one after 24 months. Additionally, one
      Platyrrhinus lineatus was captured at about 20 km, after 26 months. As they moved
      around over considerable distances and are not monogamous, they mate with females
      of other fragments, exchanging genes and reducing or even avoiding inbreeding.
      Thus, populations of bats have the ability to increase genetic diversity in
      metapopulations, provided by displacements between the forest fragments. Species
      that behave like this are not vulnerable to isolation.

PMID- 22990834
TI  - New hosts and parasitism notes for the mite Leptus (Acari: Erythraeidae) in
      fragments of the Atlantic Forest, Brazil.
AB  - New hosts and parasitism notes for the mite Leptus (Acari: Erythraeidae) in
      Brazil. Larval erythraeid mites are common ectoparasites of harvestmen
      (Opiliones). Studies describing insects as potential hosts have received little
      attention. Specimens of an undescribed species of the genus Leptus were collected
      in association with predatory and phytophagous Heteroptera bugs in a secondary
      forest in Vicosa, Minas Gerais state, Brazil. New mite-host records and
      information on seasonality of this mite are presented.

PMID- 22990835
TI  - Do young Carollia perspicillata (Chiroptera: Phyllostomidae) present higher
      infestation rates of Streblidae (Diptera)?
AB  - Ecological aspects related to parasitism are one of the less studied issues in
      parasitology research, and the scarce evidence available supports that younger
      specimens present higher infestation rates. The purpose of this work is to
      establish if higher infestation rates are observed in nursing females and their
      young captured inside their roost. Bats were captured inside a shelter located in
      RPPN Estacao Veracel, Santa Cruz de Cabralia, Bahia state, Brazil. A total of 56
      individuals of Carollia perspicillata were observed, 17 captured inside the roost
      during the day and 39 in trails at night. Captures of C. perspicillata during the
      day in a shelter yielded similar infestation rates to bats netted in trails and
      higher prevalence. The hypothesis that young were more infected was confirmed,
      based on the higher infestation of nursing females with neonates and on the
      significant inverse relation between body weight and number of parasites in young
      and subadults.

PMID- 22990836
TI  - Morphometrics and ratio of body proportionality of tadpoles of Rhinella icterica
      (Anura, Bufonidae) at different developmental stages.
AB  - The plasticity of the anurans' development is probably related to their great
      ecological and geographic diversity. Therefore, the understanding of
      environmental occupation by tadpoles is related to their morphological
      peculiarities. We evaluated the morphologic development of the larval phases 23,
      25, 30, 37, 39 and 42 of Rhinella icterica with the aim of establishing the ratio
      of growth, the increase in corporal mass in relation to growth and the isometry
      of the corporal variables for each evaluated stage. We submitted the corporal
      variables to the Multivariate Allometry and the relation between these variables
      was evaluated using the Principal Components Analysis. We verified the isometric
      growth and correlation between the different variables, evaluated the growth
      according to the body mass and established the proportionality ratio between the
      corporal regions. Each corporal region evaluated presented a fixed
      proportionality ratio, regardless of the stage, and the size of this portion was
      found when its proportionality index was multiplied by the tadpole's total
      length. This study demonstrates that the larval phase of R. icterica presents an
      isometric growth with proportional development of the corporal parts regardless
      of the evaluated stage.

PMID- 22990838
TI  - The conservation of neotropical biodiversity: the road to sustainability.

PMID- 22990837
TI  - First report of infestation of cassava fruit, Manihot esculenta, by Neosilba
      perezi (Romero & Ruppell) (Lonchaeidae) in Brazil.

PMID- 22990839
TI  - An empirical mathematical model applied to quantitative evaluation of
      thioacetamide-induced acute liver injury in rats by use of dynamic contrast
      enhanced computed tomography.
AB  - Our purpose in this study was to apply an empirical mathematical model (EMM) to
      the quantitative evaluation of thioacetamide (TAA)-induced acute liver injury in
      rats by use of dynamic contrast-enhanced computed tomography (DCE-CT), and to
      investigate its usefulness in comparison with a dual-input, single-compartment
      model. The rats in the TAA-treated group were injected intravenously with 140
      mg/kg body weight (n = 10) or 280 mg/kg body weight (n = 10) of TAA, whereas
      those in the control group (n = 10) were injected with saline instead of TAA. The
      DCE-CT studies were performed 2 days after injection of TAA or saline by use of a
      4-detector row CT. The upper limit of the time-density curve (A), the rates of
      contrast uptake (alpha) and washout (beta), the parameter related to the slope of
      early uptake (q), the area under the curve (AUC), the time to the maximum
      enhancement (T (max)), the maximum enhancement (C (Lmax)), and the elimination
      half-life of the contrast agent (T (1/2)) were calculated by use of the EMM.
      Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were
      also measured. Both alpha and q decreased significantly in the rats of the TAA
      treated group compared to those in the control group, whereas T (max) and T (1/2)
      increased significantly. The values of alpha, q, AUC, and T (max) were
      significantly correlated with both AST and ALT. Our results suggest that the EMM
      is useful for quantitative evaluation of TAA-induced acute liver injury and can
      be used as an alternative to the dual-input single-compartment model, especially
      when the vascular input functions cannot be obtained.

PMID- 22990841
TI  - Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase
      and D-amino acid oxidase.
AB  - For elucidation of the regulation mechanisms of intrinsic amounts of D-serine (D
      Ser) which modulates the neuro-transmission of N-methyl-D-aspartate receptors in
      the brain, mutant animals lacking serine racemase (SRR) and D-amino acid oxidase
      (DAO) were established, and the amounts of D-Ser in the tissues and physiological
      fluids were determined. D-Ser amounts in the frontal brain areas were drastically
      decreased followed by reduced SRR activity. On the other hand, a moderate but
      significant decrease in D-Ser amounts was observed in the cerebellum and spinal
      cord of SRR knock-out (SRR(-/-)) mice compared with those of control mice,
      although the amounts of D-Ser in these tissues were low. The amounts of D-Ser in
      the brain and serum were not altered with aging. To clarify the uptake of
      exogenous D-Ser into the brain tissues, we have determined the D-Ser of SRR(-/-)
      mice after oral administration of D-Ser for the first time, and a drastic
      increase in D-Ser amounts in all the tested tissues was observed. Because both
      DAO and SRR are present in some brain areas, we have established the double
      mutant mice lacking SRR and DAO for the first time, and the contribution of both
      enzymes to the intrinsic D-Ser amounts was investigated. In the frontal brain,
      most of the intrinsic D-Ser was biosynthesized by SRR. On the other hand, half of
      the D-Ser present in the hindbrain was derived from the biosynthesis by SRR.
      These results indicate that the regulation of intrinsic D-Ser amounts is
      different depending on the tissues and provide useful information for the
      development of treatments for neuronal diseases.

PMID- 22990842
TI  - Effect of oxygen deficiency on nitrogen assimilation and amino acid metabolism of
      soybean root segments.
AB  - Plants submitted to O(2) deficiency present a series of biochemical
      modifications, affecting overall root metabolism. Here, the effect of hypoxia on
      the metabolic fate of (15)N derived from (15)NO(3)(-), (15)NO(2)(-) and
      (15)NH(4)(+) in isolated soybean root segments was followed by gas chromatography
      mass spectrometry, to provide a detailed analysis of nitrogen assimilation and
      amino acid biosynthesis under hypoxia. O(2) deficiency decreased the uptake of
      the nitrogen sources from the solution, as ratified by the lower (15)NO(3)(-) and
      (15)NH(4)(+) enrichment in the root segments. Moreover, analysis of endogenous
      NO(2)(-) and (15)NH(4)(+) levels suggested a slower metabolism of these ions
      under hypoxia. Accordingly, regardless of the nitrogen source, hypoxia reduced
      total (15)N incorporation into amino acids. Analysis of (15)N enrichment patterns
      and amino acid levels suggest a redirecting of amino acid metabolism to alanine
      and gamma-aminobutyric acid synthesis under hypoxia and a differential
      sensitivity of individual amino acid pathways to this stress. Moreover, the role
      of glutamine synthetase in nitrogen assimilation both under normoxia and hypoxia
      was ratified. In comparison with (15)NH(4)(+), (15)NO(2)(-) assimilation into
      amino acids was more strongly affected by hypoxia and NO(2)(-) accumulated in
      root segments during this stress, indicating that nitrite reductase may be an
      additional limiting step. NO(2)(-) accumulation was associated with a higher
      nitric oxide emission. (15)NO(3)(-) led to much lower (15)N incorporation in both
      O(2) conditions, probably due to the limited nitrate reductase activity of the
      root segments. Overall, the present work shows that profound alterations of root
      nitrogen metabolism occur during hypoxic stress.

PMID- 22990843
TI  - Glutamate induces neutrophil cell migration by activating class I metabotropic
      glutamate receptors.
AB  - Leukocytes are recruited at the site of infection or injury as a part of the
      innate immune system, and play a very critical role in fighting the invading
      microorganisms and/or healing wounds. Neutrophils are the most abundant
      leukocytes in healthy humans and are the principal cell types that arrive at the
      target site in the initial phase of this process. Previous studies from our
      laboratory have shown that the amino acid glutamate is a novel chemotaxis
      inducing factor for human neutrophils. In this report, we provide evidences that
      clearly demonstrate that the glutamate-induced neutrophil cell migration activity
      is mediated by the class I metabotropic glutamate receptors. Our results further
      show that a specific integrin beta2 (ITG beta2) receptor, namely LFA1
      (alpha(L)beta(2)) is activated upon glutamate treatment and is required for
      further downstream signaling events leading to increased migration of human
      neutrophil cells. Following glutamate stimulation, LFA1 is phosphorylated by the
      Src Kinase Lck at the Y735 residue, which triggers a downstream signaling cascade
      leading to activation of PI3K, Syk, Vav and finally the Rho family GTPase, Rac2.
      Interestingly, glutamate was previously found to be present in elevated levels in
      wound fluid. Furthermore, glutamate level was also found to go up following
      inflammation. Taken together, our study suggests a novel mode of neutrophil
      recruitment to the target site following an infection or injury.

PMID- 22990844
TI  - Retooling existing tuberculosis drugs for children.

PMID- 22990845
TI  - Editorial commentary: fecal microbiota transplantation: patient and physician
      attitudes.

PMID- 22990846
TI  - Reply to Seddon, Schaaf, and Hesseling.

PMID- 22990847
TI  - Pneumocystis jirovecii genotypes involved in pneumocystis pneumonia outbreaks
      among renal transplant recipients.

PMID- 22990848
TI  - State-of-the-art monitoring of cytomegalovirus-specific cell-mediated immunity
      after organ transplant: a primer for the clinician.
AB  - Cytomegalovirus (CMV) is one of the most common infections after solid organ
      transplantation. Improved assays to predict viral replication and disease would
      help refine current preventive strategies. Monitoring of CMV-specific T-cell
      responses may help guide clinical decision making. Several techniques are now
      available to quantify CMV-specific T-cell responses, including flow cytometry,
      enzyme-linked immunosorbent spot assay, and enzyme-linked immunosorbent assay.
      Standardization and validation of these assays have the potential to
      significantly change the monitoring and treatment of CMV and further personalize
      CMV prevention strategies. In this review, we discuss the measurement of CMV
      specific T-cell responses and their clinical impact on the management of CMV
      after organ transplantation.

PMID- 22990849
TI  - Patient attitudes toward the use of fecal microbiota transplantation in the
      treatment of recurrent Clostridium difficile infection.
AB  - BACKGROUND: Fecal microbiota transplantation (FMT), a safe, effective alternative
      therapy for recurrent Clostridium difficile infection (CDI), is infrequently
      used, in part because of an assumption that patients are unwilling to consider
      FMT because of its unappealing nature. METHODS: Through a structured survey,
      including hypothetical case scenarios, we assessed patient perceptions of the
      aesthetics of FMT and their willingness to consider it as a treatment option,
      when presented with scenarios involving recurrent CDI. RESULTS: Four hundred
      surveys were distributed; 192 (48%) were returned complete. Seventy percent of
      respondents were female; 59% were >49 years of age. When provided efficacy data
      only, 162 respondents (85%) chose to receive FMT, and 29 (15%) chose antibiotics
      alone. When aware of the fecal nature of FMT, 16 respondents changed their choice
      from FMT to antibiotics alone, but there was no significant change in the total
      number choosing FMT (154 [81%]; P = .15). More respondents chose FMT if offered
      as a pill (90%; P = .002) or if their physician recommended it (94%; P < .001).
      Respondents rated all aspects of FMT at least "somewhat unappealing," selecting
      "the need to handle stool" and "receiving FMT by nasogastric tube" as most
      unappealing. Women rated all aspects of FMT more unappealing; older respondents
      rated all aspects less unappealing. Most respondents preferred to receive FMT in
      the hospital (48%) or physician's office (39%); 77% were willing to pay out-of
      pocket for FMT. CONCLUSIONS: Patients recognize the inherently unappealing nature
      of FMT, but they are nonetheless open to considering it as a treatment
      alternative for recurrent CDI, especially when recommended by a physician.

PMID- 22990850
TI  - Reply to Hauser et Al.

PMID- 22990851
TI  - Nosocomial infections in adult cardiogenic shock patients supported by
      venoarterial extracorporeal membrane oxygenation.
AB  - BACKGROUND: Incidence and impact on adult patients' outcomes of nosocomial
      infections (NIs) occurring during venoarterial extracorporeal membrane
      oxygenation (VA-ECMO) support for refractory cardiogenic shock have rarely been
      described. METHODS: We retrospectively reviewed the charts of a large series of
      patients who received VA-ECMO in our intensive care unit (ICU) from January 2003
      through December 2009. Incidence, types, risk factors, and impact on outcomes of
      NIs occurring during ECMO support were analyzed. RESULTS: Among 220 patients (49
      +/- 16 years old, simplified acute physiology score (SAPS) II 61 +/- 20) who
      underwent ECMO support for >48 hours for a total of 2942 ECMO days, 142 (64%)
      developed NIs. Ventilator-associated pneumonia (VAP), bloodstream infections,
      cannula infections, and mediastinitis infections occurred in 55%, 18%, 10% and
      11% of the patients, respectively. More critical condition at ICU admission, but
      not antibiotics at the time of ECMO cannulation, was associated with subsequently
      developing NIs (hazard ratio, 0.73; 95% confidence interval [CI], .50-1.05; P =
      .09). Infected patients had longer durations of mechanical ventilation, ECMO
      support, and hospital stays. Independent predictors of death were infection with
      severe sepsis or septic shock (odds ratio, 1.93; 95% CI, 1.26-2.94; P = .002) and
      SAPS II, whereas immunosuppression and myocarditis as the reason for ECMO support
      were associated with better outcomes. CONCLUSIONS: Cardiogenic shock patients who
      received the latest generation VA-ECMO still had a high risk of developing NIs,
      particularly VAP. Strategies aimed at preventing these infections may improve the
      outcomes of these critically ill patients.

PMID- 22990852
TI  - Baseline characteristics and mortality among people in care for chronic viral
      hepatitis: the chronic hepatitis cohort study.
AB  - BACKGROUND: The Chronic Hepatitis Cohort Study (CHeCS), a dynamic prospective,
      longitudinal, observational cohort study, was created to assess the clinical
      impact of chronic viral hepatitis in the United States. This report describes the
      cohort selection process, baseline demographics, and insurance, biopsy,
      hospitalization, and mortality rates. METHODS: Electronic health records of >1.6
      million adult patients seen from January 2006 through December 2010 at 4
      integrated healthcare systems in Detroit, Michigan; Danville, Pennsylvania;
      Portland, Oregon; and Honolulu, Hawaii were collected and analyzed. RESULTS: Of
      2202 patients with chronic hepatitis B virus (HBV) infection, 50% were aged 44-63
      years, 57% male, 58% Asian/Pacific Islander, and 13% black; and 5.1% had
      Medicaid, 16.5% Medicare, and 76.3% private insurance. During 2001-2010, 22.3%
      had a liver biopsy and 37.9% were hospitalized. For the 8810 patients with
      chronic hepatitis C virus (HCV) infection, 75% were aged 44-63 years, 60% male,
      23% black; and 12% had Medicaid, 23% Medicare, and 62% private insurance. During
      2001-2010, 38.4% had a liver biopsy and 44.3% were hospitalized. Among persons in
      care, 9% of persons with HBV and 14% of persons with HCV infection, mainly those
      born during 1945-1964, died during the 2006-2010 five-year period. CONCLUSIONS:
      Baseline demographic, hospitalization, and mortality data from CHeCS highlight
      the substantial US health burden from chronic viral hepatitis, particularly among
      persons born during 1945-1964.

PMID- 22990853
TI  - Poor nutritional status of older subacute patients predicts clinical outcomes and
      mortality at 18 months of follow-up.
AB  - BACKGROUND/OBJECTIVES: Older malnourished patients experience increased surgical
      complications and greater morbidity compared with their well-nourished
      counterparts. This study aimed to assess whether nutritional status at hospital
      admission predicted clinical outcomes at 18 months follow-up. SUBJECTS/METHODS: A
      retrospective analysis of N=2076 patient admissions (65+ years) from two subacute
      hospitals, New South Wales, Australia. Analysis of outcomes at 18 months,
      according to nutritional status at index admission, was performed in a subsample
      of n = 476. Nutritional status was determined within 72 h of admission using the
      Mini Nutritional Assessment (MNA). Outcomes, obtained from electronic patient
      records, included hospital readmission rate, total Length of Stay (LOS), change
      in level of care at discharge and mortality. Survival analysis, using a Cox
      proportional hazards model, included age, sex, Major Disease Classification,
      mobility and LOS at index admission as covariates. RESULTS: At baseline, 30% of
      patients were malnourished and 53% were at risk of malnutrition. LOS was higher
      in malnourished and at risk, compared with well-nourished patients (median
      (interquartile range): 34 (21, 58); 26 (15, 41); 20 (14, 26) days, respectively;
      P<0.001). Hazard rate for death in the malnourished group is 3.41 (95% confidence
      interval: 1.07-10.87; P = 0.038) times the well-nourished group. Discharge to a
      higher level of residential care was 33.1%, 16.9% and 4.9% for malnourished, at
      risk and well-nourished patients, respectively; P <= 0.001). CONCLUSION:
      Malnutrition in elderly subacute patients predicts adverse clinical outcomes and
      identifies a need to target this population for nutritional intervention
      following hospital discharge.

PMID- 22990854
TI  - Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri
      NCIMB 30242: a randomized controlled trial.
AB  - BACKGROUND/OBJECTIVES: The percentage of hypercholesterolemic individuals not
      reaching their LDL-cholesterol (LDL-C) goal remains high and additional
      therapeutic strategies should be evaluated. The objective of this study was to
      evaluate the cholesterol-lowering efficacy and mechanism of action of bile salt
      hydrolase-active Lactobacillus reuteri NCIMB 30242 capsules in
      hypercholesterolemic adults. SUBJECTS/METHODS: A total of 127 subjects completed
      a randomized, double-blind, placebo-controlled, parallel-arm, multicenter study.
      Subjects were randomized to consume L. reuteri NCIMB 30242 capsules or placebo
      capsules over a 9-week intervention period. The primary outcome was LDL-C
      relative to placebo at the study end point. RESULTS: L. reuteri NCIMB 30242
      capsules reduced LDL-C by 11.64% (P<0.001), total cholesterol by 9.14%,
      (P<0.001), non-HDL-cholesterol (non-HDL-C) by 11.30% (P < 0.001) and apoB-100 by
      8.41% (P = 0.002) relative to placebo. The ratios of LDL-C/HDL-cholesterol (HDL
      C) and apoB-100/apoA-1 were reduced by 13.39% (P = 0.006) and 9.00% (P = 0.026),
      respectively, relative to placebo. Triglycerides and HDL-C were unchanged. High
      sensitivity C-reactive protein and fibrinogen were reduced by 1.05 mg/l (P =
      0.005) and 14.25% (P = 0.004) relative to placebo, respectively. Mean plasma
      deconjugated bile acids were increased by 1.00 nmol/l (P=0.025) relative to
      placebo, whereas plasma campesterol, sitosterol and stigmasterol were decreased
      by 41.5%, 34.2% and 40.7%, respectively. CONCLUSIONS: The present results suggest
      that the deconjugation of intraluminal bile acids results in reduced absorption
      of non-cholesterol sterols and indicate that L. reuteri NCIMB 30242 capsules may
      be useful as an adjunctive therapy for treating hypercholesterolemia.

PMID- 22990855
TI  - Diet costs and energy density in the diet of German children and adolescents.
AB  - This study examined the association between energy density (ED, g/kJ) and diet
      costs (?[euro]/day) in a sample of 494 German children and adolescents aged 4-18
      years using 1100 3-day-weighed dietary records from the Dortmund Nutritional and
      Anthropometric Longitudinally Designed (DONALD) Study (open cohort study) and
      retail food prices of 341 empirically selected recorded food items including
      special brands. ED was negatively associated with diet costs (beta=-0.20 kJ/g,
      P<0.0007) with a non-linear term (beta=0.01 kJ/g*kJ/g, P=0.0440). Diet costs
      increased with age (beta=0.32 yr, P<0.0001) with a negative non-linear term
      (beta=-0.01 yr*yr; P<0.0001). In conclusion, the inverse association between diet
      costs and ED was more pronounced in the older than in the younger age groups and
      in low-ED diets than in high-ED diets. Higher % diet costs of fruit/vegetables
      could be compensated by lower % diet costs of meat/sausage to lower ED without
      increasing diet costs.

PMID- 22990856
TI  - Validation of a FFQ for estimating omega-3, omega-6 and trans fatty acid intake
      during pregnancy using mature breast milk and food recalls.
AB  - BACKGROUND/OBJECTIVES: To assess the performance of a food frequency
      questionnaire (FFQ) for estimating omega-3, omega-6 and trans fatty acid intake
      during pregnancy. Moreover, we determined whether the fatty acid composition of
      mature breast milk represents a valuable biomarker for fatty acid intake during
      pregnancy. SUBJECTS/METHODS: A prospective study in 41 pregnant women, aged 18-35
      years, was conducted. Food intake during pregnancy was evaluated by three 24-h
      recalls (24 hR), and 2 FFQ. The fatty acid composition of mature breast milk was
      determined by gas chromatography. The method of triads and joint classification
      between quartiles of intake were applied. RESULTS: The FFQ was accurate for
      estimating docosahexanoic (DHA), linoleic and total omega-6 fatty acids according
      to validity coefficients. Higher agreements (>70%) into the same or adjacent
      quartiles between the dietary methods were found for alpha-linolenic, total omega
      3, linoleic and trans fatty acid intake. High validity coefficients for
      eicosapentanoic (EPA) and DHA acids of human milk were found (0.61 and 0.73,
      respectively), and the method was adequate for categorizing the intake of alpha
      linolenic, total omega-3 and trans fatty acids compared with FFQ estimates, and
      for arachidonic acid and trans fatty acids compared with food recall estimates,
      during pregnancy. CONCLUSIONS: The FFQ was an accurate tool for categorizing
      alpha-linolenic, total omega-3 and trans fatty acid intake. According to the
      validity coefficients observed, the FFQ accurately estimated DHA, linoleic and
      total omega-6 fatty acids and the composition of mature breast milk was shown to
      be a suitable biomarker for EPA and DHA fatty acid intake during pregnancy.

PMID- 22990857
TI  - p47 negatively regulates IKK activation by inducing the lysosomal degradation of
      polyubiquitinated NEMO.
AB  - The persistent or excess activation of NF-kappaB causes various inflammatory and
      autoimmune diseases, but the molecular mechanisms that negatively regulate NF
      kappaB activation are not fully understood. Here we show that p47, an essential
      factor for Golgi membrane fusion, associates with the NEMO subunit of the IkappaB
      kinase (IKK) complex upon TNF-alpha or IL-1 stimulation, and inhibits IKK
      activation. p47 binds to Lys63-linked and linear polyubiquitin chains, which are
      conjugated to NEMO upon such stimulation. The binding of p47 to polyubiquitinated
      NEMO triggers the lysosomal degradation of NEMO, thereby inhibiting IKK
      activation. The silencing of p47 results in enhanced TNF-alpha- or IL-1-induced
      IKK activation, and an increased expression of genes encoding inflammatory
      mediators. Taken together, our results suggest that p47 is critical for
      negatively regulating stimulation-induced IKK activation in a manner that is
      mechanistically distinct from the previously characterized negative regulators,
      such as A20 and CYLD.

PMID- 22990859
TI  - The elusive Heisenberg limit in quantum-enhanced metrology.
AB  - Quantum precision enhancement is of fundamental importance for the development of
      advanced metrological optical experiments, such as gravitational wave detection
      and frequency calibration with atomic clocks. Precision in these experiments is
      strongly limited by the 1/?N shot noise factor with N being the number of probes
      (photons, atoms) employed in the experiment. Quantum theory provides tools to
      overcome the bound by using entangled probes. In an idealized scenario this gives
      rise to the Heisenberg scaling of precision 1/N. Here we show that when
      decoherence is taken into account, the maximal possible quantum enhancement in
      the asymptotic limit of infinite N amounts generically to a constant factor
      rather than quadratic improvement. We provide efficient and intuitive tools for
      deriving the bounds based on the geometry of quantum channels and semi-definite
      programming. We apply these tools to derive bounds for models of decoherence
      relevant for metrological applications including: depolarization, dephasing,
      spontaneous emission and photon loss.

PMID- 22990858
TI  - Production of alpha-L-iduronidase in maize for the potential treatment of a human
      lysosomal storage disease.
AB  - Lysosomal storage diseases are a class of over 70 rare genetic diseases that are
      amenable to enzyme replacement therapy. Towards developing a plant-based enzyme
      replacement therapeutic for the lysosomal storage disease mucopolysaccharidosis
      I, here we expressed alpha-L-iduronidase in the endosperm of maize seeds by a
      previously uncharacterized mRNA-targeting-based mechanism. Immunolocalization,
      cellular fractionation and in situ RT-PCR demonstrate that the alpha-L
      iduronidase protein and mRNA are targeted to endoplasmic reticulum (ER)-derived
      protein bodies and to protein body-ER regions, respectively, using regulatory (5'
      and 3'-UTR) and signal-peptide coding sequences from the gamma-zein gene. The
      maize alpha-L-iduronidase exhibits high activity, contains high-mannose N-glycans
      and is amenable to in vitro phosphorylation. This mRNA-based strategy is of
      widespread importance as plant N-glycan maturation is controlled and the
      therapeutic protein is generated in a native form. For our target enzyme, the N
      glycan structures are appropriate for downstream processing, a prerequisite for
      its potential as a therapeutic protein.

PMID- 22990860
TI  - Tunable ferroelectricity in artificial tri-layer superlattices comprised of non
      ferroic components.
AB  - Heterostructured material systems devoid of ferroic components are presumed not
      to display ordering associated with ferroelectricity. In heterostructures
      composed of transition metal oxides, however, the disruption introduced by an
      interface can affect the balance of the competing interactions among electronic
      spins, charges and orbitals. This has led to the emergence of properties absent
      in the original building blocks of a heterostructure, including metallicity,
      magnetism and superconductivity. Here we report the discovery of ferroelectricity
      in artificial tri-layer superlattices consisting solely of non-ferroelectric
      NdMnO(3)/SrMnO(3)/LaMnO(3) layers. Ferroelectricity was observed below 40 K
      exhibiting strong tunability by superlattice periodicity. Furthermore,
      magnetoelectric coupling resulted in 150% magnetic modulation of the
      polarization. Density functional calculations indicate that broken space
      inversion symmetry and mixed valency, because of cationic asymmetry and
      interfacial polar discontinuity, respectively, give rise to the observed
      behaviour. Our results demonstrate the engineering of asymmetric layered
      structures with emergent ferroelectric and magnetic field tunable functions
      distinct from that of normal devices, for which the components are typically
      ferroelectrics.

PMID- 22990861
TI  - First-order coil-globule transition driven by vibrational entropy.
AB  - By shifting the balance between conformational entropy and internal energy,
      polymers modify their shape under external stimuli, such as changes in
      temperature. Prominent among such transformations is the coil-globule transition,
      whereby a polymer can switch from an entropy-dominated coil conformation to a
      globular one, governed by energy. The nature of the coil-globule transition has
      remained elusive, with evidence for both continuous and discontinuous
      transitions, with the two-state behaviour of proteins as an instance of the
      latter. Theoretical models mostly predict second-order transitions. Here we
      introduce a model that takes into consideration hitherto neglected features
      common to any polymer. We show that a first-order phase transition smoothly
      appears as a function of the model parameters. Our results can relieve part of
      the conflicts between theory and experiments in the field of protein folding, in
      the wake of recent studies tracing back the remarkable properties of proteins to
      basic polymer physics.

PMID- 22990862
TI  - Dynamic evolution of venom proteins in squamate reptiles.
AB  - Phylogenetic analyses of toxin gene families have revolutionised our
      understanding of the origin and evolution of reptile venoms, leading to the
      current hypothesis that venom evolved once in squamate reptiles. However, because
      of a lack of homologous squamate non-toxin sequences, these conclusions rely on
      the implicit assumption that recruitments of protein families into venom are both
      rare and irreversible. Here we use sequences of homologous non-toxin proteins
      from two snake species to test these assumptions. Phylogenetic and ancestral
      state analyses revealed frequent nesting of 'physiological' proteins within venom
      toxin clades, suggesting early ancestral recruitment into venom followed by
      reverse recruitment of toxins back to physiological roles. These results provide
      evidence that protein recruitment into venoms from physiological functions is not
      a one-way process, but dynamic, with reversal of function and/or co-expression of
      toxins in different tissues. This requires a major reassessment of our previous
      understanding of how animal venoms evolve.

PMID- 22990863
TI  - Controllable chirality-induced geometrical Hall effect in a frustrated highly
      correlated metal.
AB  - A current of electrons traversing a landscape of localized spins possessing non
      coplanar magnetic order gains a geometrical (Berry) phase, which can lead to a
      Hall voltage independent of the spin-orbit coupling within the material-a
      geometrical Hall effect. Here we show that the highly correlated metal UCu(5)
      possesses an unusually large controllable geometrical Hall effect at T<1.2 K due
      to its frustration-induced magnetic order. The magnitude of the Hall response
      exceeds 20% of the nu=1 quantum Hall effect per atomic layer, which translates
      into an effective magnetic field of several hundred Tesla acting on the
      electrons. The existence of such a large geometric Hall response in UCu(5) opens
      a new field of enquiry into the importance of the role of frustration in highly
      correlated electron materials.

PMID- 22990864
TI  - Observation of Landau levels in potassium-intercalated graphite under a zero
      magnetic field.
AB  - The charge carriers in graphene are massless Dirac fermions and exhibit a
      relativistic Landau-level quantization in a magnetic field. Recently, it has been
      reported that, without any external magnetic field, quantized energy levels have
      been also observed from strained graphene nanobubbles on a platinum surface,
      which were attributed to the Landau levels of massless Dirac fermions in graphene
      formed by a strain-induced pseudomagnetic field. Here we show the generation of
      the Landau levels of massless Dirac fermions on a partially potassium
      intercalated graphite surface without applying external magnetic field. Landau
      levels of massless Dirac fermions indicate the graphene character in partially
      potassium-intercalated graphite. The generation of the Landau levels is ascribed
      to a vector potential induced by the perturbation of nearest-neighbour hopping,
      which may originate from a strain or a gradient of on-site potentials at the
      perimeters of potassium-free domains.

PMID- 22990865
TI  - Time-domain classification of charge-density-wave insulators.
AB  - Distinguishing insulators by the dominant type of interaction is a central
      problem in condensed matter physics. Basic models include the Bloch-Wilson and
      the Peierls insulator due to electron-lattice interactions, the Mott and the
      excitonic insulator caused by electron-electron interactions, and the Anderson
      insulator arising from electron-impurity interactions. In real materials,
      however, all the interactions are simultaneously present so that classification
      is often not straightforward. Here, we show that time- and angle-resolved
      photoemission spectroscopy can directly measure the melting times of electronic
      order parameters and thus identify-via systematic temporal discrimination of
      elementary electronic and structural processes-the dominant interaction.
      Specifically, we resolve the debates about the nature of two peculiar charge
      density-wave states in the family of transition-metal dichalcogenides, and show
      that Rb intercalated 1T-TaS(2) is a Peierls insulator and that the ultrafast
      response of 1T-TiSe(2) is highly suggestive of an excitonic insulator.

PMID- 22990866
TI  - Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium
      of distinct lineage-specified progenitors.
AB  - The pluripotent nature of human embryonic stem cells (hESCs) makes them
      convenient for deriving therapeutically relevant cells. Here we show using Wnt
      reporter hESC lines that the cells are heterogeneous with respect to endogenous
      Wnt signalling activity. Moreover, the level of Wnt signalling activity in
      individual cells correlates with differences in clonogenic potential and lineage
      specific differentiation propensity. The addition of Wnt protein or, conversely,
      a small-molecule Wnt inhibitor (IWP2) reduces heterogeneity, allowing stable
      expansion of Wnt(high) or Wnt(low) hESC populations, respectively. On
      differentiation, the Wnt(high) hESCs predominantly form endodermal and cardiac
      cells, whereas the Wnt(low) hESCs generate primarily neuroectodermal cells. Thus,
      heterogeneity with respect to endogenous Wnt signalling underlies much of the
      inefficiency in directing hESCs towards specific cell types. The relatively
      uniform differentiation potential of the Wnt(high) and Wnt(low) hESCs leads to
      faster and more efficient derivation of targeted cell types from these
      populations.

PMID- 22990867
TI  - Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of
      mouse embryos.
AB  - The differentiation and patterning of murine early embryos are sustained by the
      visceral endoderm, an epithelial layer of polarised cells that has critical roles
      in multiple signalling pathways and nutrient uptake. Both nutritional and
      signalling functions rely upon the endocytosis of various molecules from the cell
      surface via the endocytic pathway. However, endocytic membrane dynamics in this
      embryonic tissue remain poorly understood. Here we show that the functions of
      rab7, a small GTP-binding protein regulating the late endocytic pathway, are
      essential for embryonic patterning during gastrulation. The endosomes of visceral
      endoderm cells are delivered via a unique microautophagy-like process to the
      apical vacuole, a large compartment exhibiting lysosomal characteristics. Loss of
      rab7 function results in severe inhibition of this endocytic pathway. Our results
      indicate that the microautophagic process and flow of the endocytic membrane have
      essential roles in early embryonic development.

PMID- 22990868
TI  - Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through
      activation of Aurora kinase B.
AB  - Although heat-shock protein 70 (HSP70), an evolutionarily highly conserved
      molecular chaperone, is known to be post-translationally modified in various ways
      such as phosphorylation, ubiquitination and glycosylation, physiological
      significance of lysine methylation has never been elucidated. Here we identify
      dimethylation of HSP70 at Lys-561 by SETD1A. Enhanced HSP70 methylation was
      detected in various types of human cancer by immunohistochemical analysis,
      although the methylation was barely detectable in corresponding non-neoplastic
      tissues. Interestingly, methylated HSP70 predominantly localizes to the nucleus
      of cancer cells, whereas most of the HSP70 protein locates to the cytoplasm.
      Nuclear HSP70 directly interacts with Aurora kinase B (AURKB) in a methylation
      dependent manner and promotes AURKB activity in vitro and in vivo. We also find
      that methylated HSP70 has a growth-promoting effect in cancer cells. Our findings
      demonstrate a crucial role of HSP70 methylation in human carcinogenesis.

PMID- 22990870
TI  - Assessment of regional lung mechanics with electrical impedance tomography can
      determine the requirement for ECMO in patients with severe ARDS.

PMID- 22990869
TI  - End-tidal carbon dioxide is better than arterial pressure for predicting volume
      responsiveness by the passive leg raising test.
AB  - PURPOSE: In stable ventilatory and metabolic conditions, changes in end-tidal
      carbon dioxide (EtCO(2)) might reflect changes in cardiac index (CI). We tested
      whether EtCO(2) detects changes in CI induced by volume expansion and whether
      changes in EtCO(2) during passive leg raising (PLR) predict fluid responsiveness.
      We compared EtCO(2) and arterial pulse pressure for this purpose. METHODS: We
      included 65 patients [Simplified Acute Physiology Score (SAPS) II = 57 +/- 19, 37
      males, under mechanical ventilation without spontaneous breathing, 15 % with
      chronic obstructive pulmonary disease, baseline CI = 2.9 +/- 1.1 L/min/m(2)] in
      whom a fluid challenge was decided due to circulatory failure and who were
      monitored by an expiratory-CO(2) sensor and a PiCCO2 device. In all patients, we
      measured arterial pressure, EtCO(2), and CI before and after a fluid challenge.
      In 40 patients, PLR was performed before fluid administration. The PLR-induced
      changes in arterial pressure, EtCO(2), and CI were recorded. RESULTS: Considering
      the whole population, the fluid-induced changes in EtCO(2) and CI were correlated
      (r (2) = 0.45, p = 0.0001). Considering the 40 patients in whom PLR was
      performed, volume expansion increased CI >= 15 % in 21 "volume responders." A PLR
      induced increase in EtCO(2) >= 5 % predicted a fluid-induced increase in CI >= 15
      % with sensitivity of 71 % (95 % confidence interval: 48-89 %) and specificity of
      100 (82-100) %. The prediction ability of the PLR-induced changes in CI was not
      different. The area under the receiver-operating characteristic (ROC) curve for
      the PLR-induced changes in pulse pressure was not significantly different from
      0.5. CONCLUSION: The changes in EtCO(2) induced by a PLR test predicted fluid
      responsiveness with reliability, while the changes in arterial pulse pressure did
      not.

PMID- 22990872
TI  - Regulation of advance directives in Italy: further considerations.

PMID- 22990871
TI  - Visual anatomical lung CT scan assessment of lung recruitability.
AB  - PURPOSE: The computation of lung recruitability in acute respiratory distress
      syndrome (ARDS) is advocated to set positive end-expiratory pressure (PEEP) for
      preventing lung collapse. The quantitative lung CT scan, obtained by manual image
      processing, is the reference method but it is time consuming. The aim of this
      study was to evaluate the accuracy of a visual anatomical analysis compared with
      a quantitative lung CT scan analysis in assessing lung recruitability. METHODS:
      Fifty sets of two complete lung CT scans of ALI/ARDS patients computing lung
      recruitment were analyzed. Lung recruitability computed at an airway pressure of
      5 and 45 cm H(2)O was defined as the percentage decrease in the
      collapsed/consolidated lung parenchyma assessed by two expert radiologists using
      a visual anatomical analysis and as the decrease in not aerated lung regions
      using a quantitative analysis computed by dedicated software. RESULTS: Lung
      recruitability was 11.3 % (interquartile range 7.39-16.41) and 15.5 %
      (interquartile range 8.18-21.43) with the visual anatomical and quantitative
      analysis, respectively. In the Bland-Altman analysis, the bias and agreement
      bands between the visual anatomical and quantitative analysis were -2.9 % (-11.8
      to +5.9 %). The ROC curve showed that the optimal cutoff values for the visual
      anatomical analysis in predicting high versus low lung recruitability was 8.9 %
      (area under the ROC curve 0.9248, 95 % CI 0.8550-0.9946). Considering this
      cutoff, the sensitivity, specificity, and diagnostic accuracy were 0.96, 0.76,
      and 0.86, respectively. CONCLUSIONS: Visual anatomical analysis can classify
      patients into those with high and low lung recruitability allowing more
      intensivists to get access to lung recruitability assessment.

PMID- 22990873
TI  - Litoribacillus peritrichatus gen. nov. sp. nov., isolated from coastal sediment
      of an amphioxus breeding zone in Qingdao, China.
AB  - A Gram-negative, strictly aerobic, motile, short rod-shaped bacterium with
      peritrichous flagella, designated JYr12(T), was isolated from sediment of an
      amphioxus breeding zone in the coastal region of Qingdao, China. Strain JYr12(T)
      was found to grow optimally at 28  degrees C, at pH 7.0 and in the presence of 2
      3 % (w/v) NaCl. The organism was determined to contain C(16:0) (28.3 %) and
      C(16:1) omega7c and/or C(16:1) omega6c (34.8 %) as the major fatty acids and
      ubiquinone-8 (90 %) as the predominant isoprenoid ubiquinone. The polar lipids
      were found to consist of phosphatidylglycerol, phosphatidylethanolamine,
      diphosphatidylglycerol and an unknown glycolipid. The G+C content of the genomic
      DNA was determined to be 42.3 mol %. Comparative 16S rRNA gene sequence analysis
      revealed that strain JYr12(T) was placed in the class Gammaproteobacteria and
      shared ~91.20, 91.18, 91.01, 90.95, 90.80 and 90.40 % sequence similarities with
      representatives of the genus Thalassolituus, Nitrincola, Oceanospirillum,
      Marinobacterium, Marinomonas and Microbulbifer, respectively. On the basis of
      phenotypic, chemotaxonomic and genotypic data, strain JYr12(T) is considered to
      represent a novel species in a new genus within the Gammaproteobacteria, for
      which the name Litoribacillus peritrichatus gen. nov., sp. nov. is proposed. The
      type strain of Litoribacillus peritrichatus is JYr12(T) (=CGMCC 1.10796(T) =
      JCM17551(T)).

PMID- 22990875
TI  - A study examining the complications associated with gastric banding.
AB  - BACKGROUND: Gastric banding is a well-recognized and common method of weight
      reduction surgery. Between November 2001 and September 2011, 1,100 laparoscopic
      adjustable gastric banding operations were performed in Sheffield. This study
      examines the long-term complication rate. METHODS: All available medical notes
      for patients undergoing gastric banding by one surgeon were reviewed. Data were
      available for 1,079 patients. RESULTS: A total of 932 females and 147 males
      underwent gastric banding. Mean weight was 120 kg, with body mass index of 43.3.
      Complications occurred in 347 patients (32.1 %). One hundred three (13.2 %)
      patients experienced band slippage; re-operation was required in half of these
      cases. Eighty-two patients had their band removed due to complications; there was
      slippage in 60, erosion in 17, and band intolerance in 5. One hundred thirty-six
      (12.6 %) patients experienced problems with their port or port tubing. Thirty
      seven ports were flipped, noted during clinical or radiological fills (3.4 %),
      and 17 patients experienced port infection (1.5 %). Fifty ports required
      repositioning (4.6 %); 16 (1.4 %) were removed or replaced including five for
      cutaneous erosion. Eleven patients experienced tubing problems. Four patients
      required procedures to deal with intraoperative complications. Eighteen patients
      had a concurrent procedure. One postoperative death was due to biliary
      peritonitis in a patient who had undergone simultaneous cholecystectomy.
      CONCLUSION: Complication rates reflect those in the literature. Slippage rate may
      appear higher in our patients, but this is a reflection of the fact that most
      patients undergo radiological band fills; hence, many non-symptomatic slippages
      are detected. Only half of our slippages (6.6 % of all patients) were clinically
      apparent or needed any intervention.

PMID- 22990877
TI  - Perception, experience and body identity.
AB  - Physician has to know the patient in the disease and not only the disease in the
      patient, from the dual perspective of the body as object and the body as subject.
      This also affects the patient who has to cope with the reality of having a body
      that bursts into the subject's consciousness as a vital threat, as source of
      discomfort and inability and being a body (Marcel). The human body in its dual
      aspect has been and is a great unknown, if not a great outrage in spite of the
      fact that we are our body and our body is each of us. We sometimes do not feel as
      we are and thus a confrontation arises, sometimes more normal, others more
      morbid. This forces the physician to face complex ethics considerations and the
      scientist to accept a personal identity disorder. Dualism considers that there
      are two substances in us, one that distinguishes us from other beings and from
      the rest of the individuals of the human species, the soul, the psychic life,
      mind or consciousness, and another more insubstancial one, the body. The aim of
      the first substance is to dominate the body, to survive it after death when it
      is, already a corpse is meant to become putrefied, is buried, incinerated or
      thrown to the depth of the sea. This dualism aims to explain the origin of the
      evil and the attitude to defeat it and it does so efficiently. This anthropology
      has very ancient roots (the Upvanishads, in the orphic texts, in Plato), it is
      the core of Gnostic thought and the foundation of the modern science since
      Descartes. Some monist perspectives are a masked dualism or a mereologic fallacy,
      according to which, the brain is conscious, when that what is conscious is the
      subject, although the subject, with the brain could not be conscious. Therefore,
      a new perspective is proposed, chiasmatic or janicular monism, that considers the
      adaptive value of focusing on the reality from two perspectives, as physical
      universe and the world of interpersonal relationships. In the agnosias and in the
      phantom limb there is a confrontation between the body object and the body
      subject that has made it possible to investigate how the perception of the own
      body is and how the brain generates the schema and the body image. The study of
      the body experience, from the phenomenology and the anthropological psychiatry
      perspective, has made it possible to go greater in-depth into the knowledge of
      the alterations of the experience of the own body in different mental diseases,
      especially in those in which a confrontation between the body and the personal
      identity arises makes it necessary to consider the process of individual
      identification and a category of personal identity disorders that would include
      body dysmorphic disorder, erythrophobia, anorexia nervosa, body integrity
      identity as well as the gender-type disorders (transsexualism, nonfetishistic
      transvestism, gender identity disorder during childhood). Key words: Dualism,
      Monism, Agnosia, Phantom limb, Cenesthesia, Body schema, Body image, Body
      experience, Personal identity disorders, Body dysmorphic disorder, Anorexia
      nervosa, Personal integrity identity disorder.

PMID- 22990874
TI  - Outcomes of revisional procedures for insufficient weight loss or weight regain
      after Roux-en-Y gastric bypass.
AB  - BACKGROUND: The Roux-en-Y gastric bypass (RYGB) performed laparoscopically
      (LRYGB) is the most frequently performed bariatric procedure in Belgium. However,
      late results in terms of weight loss or weight regain are inconsistent and may
      warrant a second procedure. This retrospective study analyzes the laparoscopic
      options for revisional surgery after LRYGB. METHODS: Between January 1, 2001 and
      December 31, 2009, 70 patients underwent a new laparoscopic procedure for poor
      weight loss or weight regain after LRYGB. The revisional procedure was performed
      a median of 2.6 years after the initial bypass operation. Fifty-eight patients
      were available for follow-up (82.9 %); 19 underwent distalization; and 39 a new
      restrictive procedure. RESULTS: The mean mass index (BMI) before the revisional
      procedure was 39.1 + 11.3 kg/m(2) (30.8-51.8), down from 42.7 + 19.7 kg/m(2)
      (33.0-56.6) initially, which corresponded to a percentage of excess weight loss
      (EWL) of 12.4 + 9.3 % (-1.0-29.1). After the corrective procedure, with a follow
      up of approximately 4 years, mean BMI was 29.6 + 12.4 kg/m(2) (18.0-45.5), for a
      significant additional percentage of EWL of 53.7 + 9.8 % (2.0-65.8). The overall
      complication rate was 20.7 %, and the reoperation rate was 7.3 %. The overall
      leak rate was 12.1 %. Patients suffering from leaks could consistently be treated
      conservatively or by stent placement. Two patients needed reconversion after
      distal bypass. The satisfaction index was good in just over 50 % of the patients.
      CONCLUSION: Revisional laparoscopic surgery after RYGB performed for weight
      issues provides good additional weight loss but carries significant morbidity.
      Leaks can usually be handled non-surgically. Patient satisfaction is only fair.

PMID- 22990878
TI  - Single molecule sensing with solid-state nanopores: novel materials, methods, and
      applications.
AB  - This tutorial review will introduce and explore the fundamental aspects of
      nanopore (bio)sensing, fabrication, modification, and the emerging technologies
      and applications that both intrigue and inspire those working in and around the
      field. Although nanopores can be classified into two categories, solid-state and
      biological, they are essentially two sides of the same coin. For instance, both
      garner popularity due to their ability to confine analytes of interest to a
      nanoscale volume. Due to the vast diversity of nanopore platforms and
      applications, no single review can cover the entire landscape of published work
      in the field. Therefore, in this article focus will be placed on recent
      advancements and developments taking place in the field of solid-state nanopores.
      It should be stated that the intention of this tutorial review is not to cite all
      articles relating to solid-state nanopores, but rather to highlight recent,
      select developments that will hopefully benefit the new and seasoned scientist
      alike. Initially we begin with the fundamentals of solid-state nanopore sensing.
      Then the spotlight is shone on the sophisticated fabrication methods that have
      their origins in the semiconductor industry. One inherent advantage of solid
      state nanopores is in the ease of functionalizing the surface with a range of
      molecules carrying functional groups. Therefore, an entire section is devoted to
      highlighting various chemical and bio-molecular modifications and explores how
      these permit the development of novel sensors with specific targets and
      functions. The review is completed with a discussion on novel detection
      strategies using nanopores. Although the most popular mode of nanopore sensing is
      based upon what has come to be known as ionic-current blockade sensing, there is
      a vast, growing literature based around exploring alternative detection
      techniques to further expand on the versatility of the sensors. Such techniques
      include optical, electronic, and force based methods. It is perhaps fair to say
      that these new frontiers have caused further excitement within the sensing
      community.

PMID- 22990879
TI  - Molecular structures of M2N2(2-) (M and N = B, Al, and Ga) clusters using the
      gradient embedded genetic algorithm.
AB  - Al(4)(2-) was the first discovered sigma + pi aromatic all-metal cluster. In the
      present work we analyze the molecular structure, relative stability, and
      aromaticity of lowest-lying isomers of related M(2)N(2)(2-) (M and N = B, Al, and
      Ga) clusters, with special emphasis devoted to the cis (C(2v)) and trans (D(2h))
      isomers of the M(2)N(2)(2-) clusters. For such purpose, we start by performing
      the search of the global minimum for each cluster through the Gradient Embedded
      Genetic Algorithm (GEGA). Energy decomposition analyses and the calculated
      magnetic- and electronic-based aromaticity criteria of the lowest-lying isomers
      help to understand the nature of the bonding and the origin of the stability of
      the global minima. Such methodology should allow guiding future molecular design
      strategies.

PMID- 22990880
TI  - Histidine ligand variants of a flavo-diiron protein: effects on structure and
      activities.
AB  - Flavo-diiron proteins (FDPs) contain non-heme diiron and proximal flavin
      mononucleotide (FMN) active sites and function as terminal components of a nitric
      oxide reductase (NOR) and/or a four-electron dioxygen reductase (O(2)R). While
      most FDPs show similar structural, spectroscopic, and redox properties, O(2)R and
      NOR activities vary significantly among FDPs. A potential source of this
      variability is the iron ligation status of a conserved His residue that provides
      an iron ligand in all known FDP structures but one, where this His residue is
      rotated away from iron and replaced by a solvent ligand. In order to test the
      effect of this His ligation status, we changed this ligating His residue (H90) in
      Thermotoga maritima (Tm) FDP to either Asn or Ala. The wild-type Tm FDP shows
      significantly higher O(2)R than NOR activity. Single crystal X-ray
      crystallography revealed a remarkably conserved diiron site structure in the H90N
      and -A variants, differing mainly by either Asn or solvent coordination,
      respectively, in place of H90. The steady-state activities were minimally
      affected by the H90 substitutions, remaining significantly higher for O(2)R
      versus NOR. The pre-steady-state kinetics of the fully reduced FDP with O(2) were
      also minimally affected by the H90 substitutions. The results indicate that the
      coordination status of this His ligand does not significantly modulate the O(2)R
      or NOR activities, and that FDPs can retain these activities when the individual
      iron centers are differentiated by His ligand substitution. This differentiation
      may have implications for the O(2)R and NOR mechanisms of FDPs.

PMID- 22990881
TI  - Individual and family predictors of the perpetration of dating violence and
      victimization in late adolescence.
AB  - Teen dating violence is a crime of national concern with approximately one-fourth
      of adolescents reporting victimization of physical, psychological, or sexual
      dating violence each year. The present study examined how aggressive family
      dynamics in both childhood and early adolescence predicted the perpetration of
      dating violence and victimization in late adolescence. Children (n = 401, 43 %
      female) were followed from kindergarten entry to the age of 18 years. Early
      adolescent aggressive-oppositional problems at home and aggressive-oppositional
      problems at school each made unique predictions to the emergence of dating
      violence in late adolescence. The results suggest that aggressive family dynamics
      during childhood and early adolescence influence the development of dating
      violence primarily by fostering a child's oppositional-aggressive responding
      style initially in the home, which is then generalized to other contexts.
      Although this study is limited by weaknesses detailed in the discussion, the
      contribution of longitudinal evidence including parent, teacher, and adolescent
      reports from both boys and girls, a dual-emphasis on the prediction of
      perpetration and victimization, as well as an analysis of both relations between
      variables and person-oriented group comparisons combine to make a unique
      contribution to the growing literature on adolescent partner violence.

PMID- 22990882
TI  - Involved-vigilant parenting and socio-emotional well-being among black youth: the
      moderating influence of natural mentoring relationships.
AB  - Positive relationships with parents and nonparental adults have the potential to
      bolster Black adolescents' socio-emotional well-being. Though each type of
      intergenerational relationship has been linked to more positive youth outcomes,
      few studies have examined the interactive influences of parenting and natural
      mentoring relationships on the socio-emotional development of Black youth. In the
      current study, we examined associations between involved-vigilant parenting and
      the psychological well-being and social skills of Black early adolescents (n =
      259; 58 % female; mean age = 13.56, SD = .96) across types of natural mentoring
      relationships. Using K-means cluster analysis, we identified two types of
      mentoring relationships (less connected and more connected) based on relationship
      length, involvement, closeness, and frequency of contact. Youth with more
      connected mentoring relationships (n = 123) had higher psychological well-being
      and social skills than youth with no mentor (n = 64) or less connected mentors (n
      = 72). Youth without a natural mentor and youth with less connected mentors did
      not differ in their levels of social skills or psychological well-being.
      Structural equation modeling was conducted to determine if associations between
      involved-vigilant parenting and youths' psychological well-being and social
      skills varied among youth with a more connected mentoring relationship in
      comparison to youth without a mentor or with a less connected mentor, controlling
      for participants' gender, age, school, and parental education. The positive
      associations between involved-vigilant parenting and adolescents' psychological
      well-being and social skills were weaker among adolescents with a more connected
      mentoring relationship in comparison to their peers without or with a less
      connected mentoring relationship. These results suggest that youth may be more
      strongly influenced by involved-vigilant parenting in the absence of a strongly
      connected natural mentoring relationship.

PMID- 22990883
TI  - A longitudinal path analysis of peer victimization, threat appraisals to the
      self, and aggression, anxiety, and depression among urban African American
      adolescents.
AB  - Threat appraisals-individuals' perceptions of how stressful situations may
      threaten their well-being-are an important but understudied mechanism that could
      explain links between peer victimization and adjustment. The goal of the present
      study was to examine relationships between physical and relational victimization
      by peers, threats to the self, and aggression, anxiety, and depression to better
      understand the cognitive evaluations that make youth vulnerable to negative
      adjustment. The sample comprised two cohorts of African American adolescents (N =
      326; 54 % female; M = 12.1; SD = 1.6) and their maternal caregivers, who
      participated in three waves of a longitudinal study. Path models revealed
      significant direct effects from Time 1 relational victimization, but not physical
      victimization, to Time 2 threat appraisals (i.e., negative self-evaluations and
      negative evaluations by others), controlling for Time 1 threat appraisals.
      Significant direct effects were found from Time 2 threats of negative evaluations
      by others to Time 3 youth-reported aggression, controlling for Time 1 and Time 2
      aggression. Significant direct effects also were found from Time 2 threats of
      negative self-evaluations to T3 youth-reported depression, controlling for Time 1
      and Time 2 depression. Overall, findings highlight the need to consider the role
      of threats to the self in pathways from peer victimization to adjustment and the
      implications these appraisals have for youth prevention and intervention efforts.

PMID- 22990884
TI  - Infective endocarditis in the transcatheter aortic valve replacement era:
      comprehensive review of a rare complication.
AB  - In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a
      revolutionary alternative for surgical aortic valve replacement (SAVR) for the
      treatment of severe symptomatic aortic stenosis in patients at high risk for
      surgery. Prosthetic aortic valve endocarditis is a serious complication after
      SAVR with high morbidity and mortality. Although numerous TAVR procedures have
      been performed worldwide, infective endocarditis (IE) after TAVR was reported in
      the literature in few cases only and in 0% to 2.3% of patients enrolled in large
      TAVR cohorts. Our aim was to review the literature for IE following TAVR and to
      discuss the diagnostic and management strategies of this rare complication. Ten
      case reports of IE after TAVR were identified, 8 of which were published as case
      reports and 2 of which were presented in congresses. Infective endocarditis
      occurred in a mean time period of 186 days (median, 90 days) after TAVR. Most
      cases were characterized by fever and elevated inflammatory markers. Infective
      endocarditis after TAVR shared some common characteristics with IE after SAVR,
      yet it has some unique features. Echocardiographic findings included leaflet
      vegetations, severe mitral regurgitation with rupture of the anterior leaflet,
      and left ventricle outflow tract to left atrium fistula. Bacteriologic findings
      included several atypical bacteria or fungi. Cases of IE were managed either
      conservatively by antibiotics and/or using surgery, and the overall prognosis was
      poor. Infective endocarditis after TAVR deserves prompt diagnosis and treatment.
      Until further evidence is present, IE after TAVR should be managed according to
      SAVR guidelines with modifications as needed on a case-by-case basis.

PMID- 22990885
TI  - Idiopathic ulcerative laryngitis causing midmembranous vocal fold granuloma.
AB  - Idiopathic ulcerative laryngitis (IUL) is characterized by bilateral
      midmembranous vocal fold ulceration, which follows upper respiratory infection
      with cough. In contrast, granuloma of the membranous vocal fold can occur rarely
      following microlaryngoscopy, presumably secondary to surgical violation of deep
      tissue planes. We report a novel case of noniatrogenic membranous vocal fold
      granulation developing in a patient with IUL. Although the presence of
      granulation implied injury to the entire microstructure of the vibratory portion
      of the vocal fold, the lesion resolved with conservative management without
      adverse sequelae.

PMID- 22990886
TI  - A balancing act.

PMID- 22990887
TI  - Maintaining system homeostasis: the third law of Newtonian immunology.
AB  - Because of the potent effector mechanisms of the immune system, the potential for
      self-destructive immune responses is especially high and many negative regulatory
      modalities exist to prevent excessive tissue damage. This Commentary places such
      regulatory mechanisms in the larger context of system organization on many
      scales. The sometimes counterintuitive nature of feedback control is discussed
      and a case is made for greater attention to quantitative spatiotemporal aspects
      of regulation, rather than limiting the discussion to the qualitative
      descriptions of pathways that dominate at present.

PMID- 22990888
TI  - Metabolic checkpoints in activated T cells.
AB  - The immunological process of clonal selection requires a rapid burst in
      lymphocyte proliferation, and this involves a metabolic shift to provide energy
      and the building blocks of new cells. After activation, naive and memory T cells
      switch from the oxidation of free fatty acids to glycolysis and glutaminolysis to
      meet these demands. Beyond this, however, the availability of specific
      metabolites and the pathways that process them interconnect with signaling events
      in the cell to influence cell cycle, differentiation, cell death and
      immunological function. Here we define 'metabolic checkpoints' that represent
      such interconnections and provide examples of how these checkpoints sense
      metabolic status and transduce signals to affect T lymphocyte responses.

PMID- 22990889
TI  - Restraint of inflammatory signaling by interdependent strata of negative
      regulatory pathways.
AB  - Activation of Toll-like receptor (TLR) signaling and related pathways by
      microbial products drives inflammatory responses, host-defense pathways and
      adaptive immunity. The cost of excessive inflammation is cell and tissue damage,
      an underlying cause of many acute and chronic diseases. Coincident with
      activation of TLR signaling, a plethora of anti-inflammatory pathways and
      mechanisms begin to modulate inflammation until tissue repair is complete.
      Whereas most studies have focused on the signaling components immediately
      downstream of the TLRs, this Review summarizes the different levels of anti
      inflammatory pathways that have evolved to abate TLR signaling and how they are
      integrated to prevent cell and tissue destruction.

PMID- 22990890
TI  - From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines.
AB  - Feedback regulatory circuits provided by regulatory T cells (T(reg) cells) and
      suppressive cytokines are an intrinsic part of the immune system, along with
      effector functions. Here we discuss some of the regulatory cytokines that have
      evolved to permit tolerance to components of self as well as the eradication of
      pathogens with minimal collateral damage to the host. Interleukin 2 (IL-2), IL-10
      and transforming growth factor-beta (TGF-beta) are well characterized, whereas IL
      27, IL-35 and IL-37 represent newcomers to the spectrum of anti-inflammatory
      cytokines. We also emphasize how information accumulated through in vitro as well
      as in vivo studies of genetically engineered mice can help in the understanding
      and treatment of human diseases.

PMID- 22990898
TI  - Securing the border: lymphotoxin, IL-23 and IL-22 keep out the bad guys and
      'fatten' the homeland.

PMID- 22990891
TI  - The price of immunity.
AB  - Resistance mechanisms of the innate and adaptive immune responses prevent the
      colonization of foreign organisms in unwanted anatomical sites and participate in
      tissue repair and restoration of homeostasis after damage induced either by the
      invasion of pathogenic microbes or by the organism's response to them. The
      intensity of the response is controlled and limited by positive and negative
      feedback circuits that aim at preventing collateral tissue damage. In this Review
      we will discuss the protective and pathogenic effects of host-commensal
      microbiota mutualism on the immune response and illustrate some examples of
      collateral tissue and systemic damage caused by immunity to pathogens.

PMID- 22990899
TI  - Yoking OX40 to regulation of IL-9.

PMID- 22990900
TI  - The Foxp3 interactome: a network perspective of T(reg) cells.

PMID- 22990907
TI  - Extraction of quantitative characteristics describing wheat leaf pubescence with
      a novel image-processing technique.
AB  - Leaf pubescence (hairiness) in wheat plays an important biological role in
      adaptation to the environment. However, this trait has always been
      methodologically difficult to phenotype. An important step forward has been taken
      with the use of computer technologies. Computer analysis of a photomicrograph of
      a transverse fold line of a leaf is proposed for quantitative evaluation of wheat
      leaf pubescence. The image-processing algorithm is implemented in the LHDetect2
      software program accessible as a Web service at http://wheatdb.org/lhdetect2 .
      The results demonstrate that the proposed method is rapid, adequately assesses
      leaf pubescence density and the length distribution of trichomes and the data
      obtained using this method are significantly correlated with the density of
      trichomes on the leaf surface. Thus, the proposed method is efficient for high
      throughput analysis of leaf pubescence morphology in cereal genetic collections
      and mapping populations.

PMID- 22990908
TI  - Disruption of sphingolipid biosynthesis in Nicotiana benthamiana activates
      salicylic acid-dependent responses and compromises resistance to Alternaria
      alternata f. sp. lycopersici.
AB  - Sphingolipids play an important role in signal transduction pathways that
      regulate physiological functions and stress responses in eukaryotes. In plants,
      recent evidence suggests that their metabolic precursors, the long-chain bases
      (LCBs) act as bioactive molecules in the immune response. Interestingly, the
      virulence of two unrelated necrotrophic fungi, Fusarium verticillioides and
      Alternaria alternata, which are pathogens of maize and tomato plants,
      respectively, depends on the production of sphinganine-analog mycotoxins (SAMs).
      These metabolites inhibit de novo synthesis of sphingolipids in their hosts
      causing accumulation of LCBs, which are key regulators of programmed cell death.
      Therefore, to gain more insight into the role of sphingolipids in plant immunity
      against SAM-producing necrotrophic fungi, we disrupted sphingolipid metabolism in
      Nicotiana benthamiana through virus-induced gene silencing (VIGS) of the serine
      palmitoyltransfersase (SPT). This enzyme catalyzes the first reaction in LCB
      synthesis. VIGS of SPT profoundly affected N. benthamiana development as well as
      LCB composition of sphingolipids. While total levels of phytosphingosine
      decreased, sphinganine and sphingosine levels increased in SPT-silenced plants,
      compared with control plants. Plant immunity was also affected as silenced plants
      accumulated salicylic acid (SA), constitutively expressed the SA-inducible NbPR-1
      gene and showed increased susceptibility to the necrotroph A. alternata f. sp.
      lycopersici. In contrast, expression of NbPR-2 and NbPR-3 genes was delayed in
      silenced plants upon fungal infection. Our results strongly suggest that LCBs
      modulate the SA-dependent responses and provide a working model of the potential
      role of SAMs from necrotrophic fungi to disrupt the plant host response to foster
      colonization.

PMID- 22990909
TI  - Nitric oxide enhances development of lateral roots in tomato (Solanum
      lycopersicum L.) under elevated carbon dioxide.
AB  - Elevated carbon dioxide (CO2) has been shown to enhance the growth and
      development of plants, especially of roots. Amongst them, lateral roots play an
      important role in nutrient uptake, and thus alleviate the nutrient limitation to
      plant growth under elevated CO2. This paper examined the mechanism underlying CO2
      elevation-induced lateral root formation in tomato. The endogenous nitric oxide
      (NO) in roots was detected by the specific probe 4-amino-5-methylamino-2',7'
      difluorofluorescein diacetate (DAF-FM DA). We suggest that CO2 elevation-induced
      NO accumulation was important for lateral root formation. Elevated CO2
      significantly increased the activity of nitric oxide synthase in roots, but not
      nitrate reductase activity. Moreover, the pharmacological evidence showed that
      nitric oxide synthase rather than nitrate reductase was responsible for CO2
      elevation-induced NO accumulation. Elevated CO2 enhanced the activity of nitric
      oxide synthase and promoted production of NO, which was involved in lateral root
      formation in tomato under elevated CO2.

PMID- 22990910
TI  - Target analysis of alpha-alkylidene-gamma-butyrolactones in uropathogenic E.
      coli.
AB  - alpha-Alkylidene-gamma-butyrolactones are quite common in nature and exhibit a
      broad spectrum of biological activities. We therefore synthesized a small library
      of xanthatine inspired alpha-alkylidene-gamma-butyrolactones to screen non
      pathogenic and uropathogenic E. coli strains by activity based protein profiling
      (ABPP). The identified targets are involved in cellular redox processes and give
      first insight into the preferred binding sites of this privileged motif.
      Furthermore the gene of one protein, c2450, which was only identified in
      uropathogenic E. coli belongs to a genomic island which encodes a hybrid
      polyketide/non-ribosomal peptide synthetase (PKS/NRPS). This system is
      responsible for the synthesis of colibactin, a natural product which causes DNA
      double strand breaks in eukaryotic cells leading to the activation of the DNA
      damage checkpoint pathway and subsequent cell cycle arrest. While the role of
      several proteins that are involved in the colibactin synthesis has been
      elucidated, the function of c2450 remains elusive. Investigation of the binding
      site showed that c2450 is modified at a cysteine residue which may be important
      for the catalytic activity.

PMID- 22990912
TI  - Health belief model and practice of breast self-examination and breast cancer
      screening in Iranian women.
AB  - OBJECTIVE: The objective of this study is to determine the role of different
      health belief model components in practice of breast cancer screening among
      Iranian women. SUBJECTS AND METHODS: A cross-sectional study of 500 women aged 18
      65 years was conducted in an urban population under the coverage of a health
      therapeutic system in Babol, northern Iran in 2012. Demographic data and data
      regarding practice of breast self-examination (BSE), breast clinical examination
      (BCE), and mammography were collected by interview, and a standard health belief
      model questionnaire was used to assess women's attitudes in six different domains
      based on a Likert scale that ranked from 1 to 5. The average score of each item
      for each domain was calculated. The Wilcoxon rank test and a multiple logistic
      regression model were used to estimate the odds ratio of each domain for
      performing breast cancer screening (BSE, BCE, and mammography). RESULTS: The mean
      age of the women was 31.2 (9.4) years. Overall, the average scores in domains of
      perceived benefit, self-efficacy, and health motivation were significantly higher
      among those who performed BSE and BCE, but not for mammography. For the domains
      of perception of susceptibility, seriousness, and barriers, no significant
      differences were observed. Higher scores on the scales of perceived benefits,
      perceived confidence/self-efficacy, and health motivation showed significant
      positive association with performing BSE [adjusted OR (95 % confidence interval
      [CI]) 1.73 (1.11, 2.72), 4.01 (2.39, 6.73), and 2.01 (1.30, 3.08), respectively]
      and BCE [adjusted OR (95 % CI) 1.65 (1.0, 2.95), 2.33 (1.39, 3.91), and 1.58
      (1.0, 2.53), respectively], but not for performing mammography. For perceived
      susceptibility, perceived seriousness, and barriers, no significant association
      was observed. CONCLUSIONS: Positive attitudes toward perceived benefits,
      perceived confidence/self-efficacy, and health motivation have a strong
      association with performing BSE and BCE. The impact of health belief model
      subscales on breast cancer screening may vary with respect to culture and values.

PMID- 22990914
TI  - Encapsulating [FeFe]-hydrogenase model compounds in peptide hydrogels
      dramatically modifies stability and photochemistry.
AB  - A [FeFe]-hydrogenase model compound (u-S(CH(2))(3)S)Fe(2)(CO)(4)(PMe(3))(2) [1]
      has been encapsulated in a low molecular weight (LMW) hydrogelator (Fmoc-Leu
      Leu). Linear infrared absorption spectroscopy, gel melting and ultrafast time
      resolved infrared spectroscopy experiments reveal significant contrasts in
      chemical environment and photochemistry between the encapsulated molecules and
      solution phase systems. Specifically, the gel provides a more rigid hydrogen
      bonding environment, which restricts isomerisation following photolysis while
      imparting significant increases in stability relative to a similarly aqueous
      solution. Since understanding and ultimately controlling the mechanistic role of
      ligands near Fe centres is likely to be crucial in exploiting artificial
      hydrogenases, these gels may offer a new option for future materials design
      involving catalysts.

PMID- 22990915
TI  - [Multimodality therapy for adenocarcinoma of the esophagogastric junction].
AB  - The definition of esophagogastric junction (EGJ) adenocarcinoma and progress in
      multidisciplinary treatment for the tumor were revised in this review. Siewert
      classification is especially useful for the surgical approach of EGJ
      adenocarcinoma. Siewert I should be treated as esophageal cancer, and Ivor-Lewis
      esophagogastrectomy (right thoracotomy and laparotomy) is recommended as an
      extended two-field lymphadenectomy. For Siewert II or III tumors, left
      thoracophreno-laparotomy is preferred, especially in case of positive thoracic
      lymph nodes or positive resection margin. If there is any contraindication
      against thoracotomy, or a high operating risk, a transhiatal esophagectomy with
      lower mediastinal lymphadenectomy is an alternative. Preoperative
      chemoradiotherapy or perioperative chemotherapy improves overall survival and the
      rate of complete resection for patients with large tumor or lymph node
      metastasis. Neoadjuvant chemoradiotherapy is associated with high but acceptable
      postoperative complications. Adjuvant chemoradiotherapy remains a rational
      standard therapy for curatively resected EGJ cancer with T3 or greater lesion or
      positive nodes.

PMID- 22990911
TI  - Modulation of distinct isoforms of L-type calcium channels by G(q)-coupled
      receptors in Xenopus oocytes: antagonistic effects of Gbetagamma and protein
      kinase C.
AB  - L-type voltage dependent Ca(2+) channels (L-VDCCs; Ca(v)1.2) are crucial in
      cardiovascular physiology. In heart and smooth muscle, hormones and transmitters
      operating via G(q) enhance L-VDCC currents via essential protein kinase C (PKC)
      involvement. Heterologous reconstitution studies in Xenopus oocytes suggested
      that PKC and G(q)-coupled receptors increased L-VDCC currents only in cardiac
      long N-terminus (NT) isoforms of alpha(1C), whereas known smooth muscle short-NT
      isoforms were inhibited by PKC and G(q) activators. We report a novel regulation
      of the long-NT alpha(1C) isoform by Gbetagamma. Gbetagamma inhibited whereas a
      Gbetagamma scavenger protein augmented the G(q)--but not phorbol ester-mediated
      enhancement of channel activity, suggesting that Gbetagamma acts upstream from
      PKC. In vitro binding experiments reveal binding of both Gbetagamma and PKC to
      alpha(1C)-NT. However, PKC modulation was not altered by mutations of multiple
      potential phosphorylation sites in the NT, and was attenuated by a mutation of C
      terminally located serine S1928. The insertion of exon 9a in intracellular loop 1
      rendered the short-NT alpha(1C) sensitive to PKC stimulation and to Gbetagamma
      scavenging. Our results suggest a complex antagonistic interplay between G(q)
      activated PKC and Gbetagamma in regulation of L-VDCC, in which multiple cytosolic
      segments of alpha(1C) are involved.

PMID- 22990916
TI  - [Staging-based minimally invasive treatment for esophageal carcinoma].
AB  - Along with continuous improvement of clinical staging modalities and endoscopic
      instrument and skills, the staging-based minimally invasive treatment for
      esophageal carcinoma has been firmly guaranteed, because of more accurate
      pretreatment staging and more mature minimally invasive technique. Different
      minimally invasive treatment should be provided to patients with different stage.
      On the premise of assurance of treatment, it would minimize trauma, accelerate
      rehabilitation, and improve quality of life.

PMID- 22990917
TI  - [Comparison of outcomes after surgery between adenocarcinoma of the
      esophagogastric junction and lower thoracic esophageal squamous cell cancer].
AB  - OBJECTIVE: To compare the differences in biological behavior and clinical
      features between adenocarcinoma of the esophagogastric junction (AEG) and lower
      thoracic esophageal squamous cell cancer (LESC), and to explore reasonable
      procedures for each cancer. METHODS: Clinical data of 111 patients with AEG and
      126 patients with LESC who underwent surgery from January 2004 to April 2012 were
      retrospectively reviewed. Data pertaining to resection rate, lymph node
      metastasis, and postoperative complication rate were analyzed. RESULTS: The
      resection rate was 94.6% for AEG and 97.6% for LESC, and the difference was not
      statistically significant (P<0.05). The rate of lymph node metastasis in the
      mediastinum in patients with AEG was significantly lower [6.3%(7/111) vs.
      32.5%(41/126), P<0.01], while the rate of lymph node metastasis in the abdomen
      was significantly higher [57.7%(64/111) vs. 34.1%(43/126), P<0.01]. The rate of
      lymph node metastasis in mediastinum of AEG was 12.5%(4/32) for Siewert I and
      4.7%(3/64) for Siewert II, and there was no lymph node metastasis in Siewert III
      (n=15). For AEG patients who underwent trans-abdominal surgery, the rate of
      positive lymph node in the middle and lower mediastinum was significantly lower
      than trans-thoracic surgery [0/22 vs. 7.9% (7/89), P<0.05]. LESC via right thorax
      with two-field or three-field lymph node dissection was associated with a
      significantly higher rate of positive lymph node metastasis in the upper
      mediastinum than that of single incision via left thorax [17.9%(12/67) vs. 0/59,
      P<0.01]. The postoperative complication rates were 23.4%(26/111) and
      27.0%(34/126) respectively, and the difference was not statistically
      significant(P>0.05). CONCLUSIONS: AEG and LESC show different lymph node
      metastasis pattern and should be operated differently. Lymphadenectomy in mid
      lower mediastinum should be emphasized in Siewert I and Siewert II type cancers.

PMID- 22990918
TI  - [Characteristics of lymphatic metastasis and surgical approach of adenocarcinoma
      of the esophagogastric junction].
AB  - OBJECTIVE: To investigate the characteristics of lymphatic metastasis in
      different types of adenocarcinoma of the esophagogastric junction (AEG) and
      provide guidance for surgical approach adoption. METHODS: Clinical data of 228
      patients with AEG undergoing surgery were analyzed retrospectively. According to
      Siewert classification, there were 9 cases of type I (3.9%) who all underwent
      left thoracoabdominal approach procedures. A total of 121 patients belonged to
      type II (53.1%), of whom 12 underwent left transthoracic approach, 48 left
      thoracoabdominal approach, and 61 transabdominal approach. Ninety-eight patients
      belonged to type III (43%), of whom 22 underwent left thoracoabdominal approach
      procedures and 76 transabdominal. The pattern of lymph node metastasis was
      analyzed and the association between surgical approach and oncological clearance
      was examined. RESULTS: The resection margin was positive in 20(8.8%) patients,
      including 10 with type II (8.3%) and 10 with type III (10.2%), and the difference
      was not statistically significant (P>0.05). The rate of positive resection margin
      was 12.4%(17/137) in the transabdominal group and 16.7%(2/12) in the left
      transthoracic group, both significantly higher than the left thoracoabdominal
      group (1.1%, 1/88) (both P<0.05). Lymph node metastasis was found in 159(69.7%)
      patients. The metastasis was found in 4 of 9 patients with type I cancer and two
      were thoracic metastasis, no metastasis was found in the upper mediastinum. For
      type II cancer, the rate of lymph node metastasis was 66.9%(81/121), including
      thoracic metastasis ( n=32, 26.4%) and abdominal metastasis (n=81, 66.9%). For
      type III cancer, the rate of lymph node metastasis was 66.9%(81/121), including
      thoracic metastasis (n=15, 15.3%) and abdominal metastasis (n=69, 70.4%).
      CONCLUSIONS: For type I AEG, left thoracoabdominal approach should be used
      because the pattern of lymph node metastasis is similar to that of the distal
      esophageal carcinoma. For type II , left thoracoabdominal approach should be used
      to ensure adequate resection of the tumor and clearance of lymph node in the
      lower esophagus and upper mediastinum because of high rate of intrathoracic lymph
      node metastasis. For type III cancer, transabdominal incision offers better
      benefit with less impact on respiratory function. However, thoracic incision
      should be used to ensure adequate clearance for tumors of larger size and
      significant external invasion.

PMID- 22990919
TI  - [Selection and evaluation of endoscopic resection for submucosal tumors of the
      esophagogastric junction originating from muscularis propria].
AB  - OBJECTIVE: To investigate the clinical application and indication of endoscopic
      dissection technique for submucosal tumors (SMTs) of the esophagogastric junction
      (EGJ) originating from the muscularis propria. METHODS: A total of 143 SMTs of
      the EGJ were treated by endoscopic resection in the Endoscopy Center of Zhongshan
      Hospital Affiliated to Fudan University between March 2007 and June 2011. The
      clinical and histopathologic feature, surgical approach, en bloc resection rate,
      complications, and postoperative follow up were evaluated. RESULTS: There were 74
      males and 69 females with a mean age of 49.1 years old. The en bloc resection
      rate was 94.4%(135/143). There were 126 patients who underwent endoscopic
      submucosal excavation in an en bloc fashion. Six patients underwent endoscopic
      full-thickness resection without laparoscopic assistance. Three patients
      underwent submucosal tunneling endoscopic resection. The other 8 SMTs were
      partially resected for histological evaluation and the residual tumors were
      further treated with nylon snare ligation. The mean lesion size was 17.6 mm. The
      mean procedure time was 45.1 minutes and the mean intraoperative bleeding was
      50.0 ml. Perforations occurred in 6 patients and metal clips were used to close
      the defect. One patient with Mallory-Weiss syndrome was successfully treated with
      conservative treatment. Pathological examination showed that the lesions were
      leiomyoma (n=121), gastrointestinal stromal tumor (n=20), granulosa cell tumor
      (n=1), and intermuscular lipoma (n=1). No local recurrence and distant metastasis
      were noted during the follow-up (range, 3-48 months). CONCLUSION: Endoscopic
      resection technique is safe and effective, and should be selected for each
      patient individually.

PMID- 22990920
TI  - [Laparoscopic transhiatal proximal gastrectomy for adenocarcinoma of the
      esophagogastric junction: report of 98 cases].
AB  - OBJECTIVE: To explore the safety and short-term efficacy of laparoscopic
      transhiatal proximal gastrectomy in patients with adenocarcinoma of the
      esophagogastric junction. METHODS: From Aug 2008 to May 2011, 98 patients with
      adenocarcinoma of the esophagogastric junction underwent laparoscopic transhiatal
      proximal gastrectomy. Clinical data were analyzed retrospectively including
      operative time, estimated bleeding, length of resection, lymph node dissection,
      and short-term postoperative complications. RESULTS: Ninety-six patients
      underwent laparoscopic transhiatal proximal gastrectomy successfully and 2 were
      converted to open operation (one for combined splenectomy and the other combined
      splenectomy and resection of the tail of the pancreas). The mean operative time
      was (224.1+/-33.7) min and the mean blood loss was (69.4+/-26.1) ml. The mean
      length of esophageal resection was (4.0+/-0.6) cm and the resection margin was
      negative. The number of lymph node removed was 16.4+/-5.7. Pleural laceration
      occurred in 14 cases and spleen injury occurred in 3 case during operation. There
      was one anastomotic leakage. There were no postoperative mortalities, bleeding,
      anastomotic stenosis and wound infection. After follow-up ranging from 3 to 30
      months, the value of reflux diagnostic questionnaire (RDQ) was 9.9+/-4.4 at 1
      month and 9.3+/-4.3 at 3 months postoperatively. No incision metastasis was found
      and 5 patients died. CONCLUSION: Laparoscopic transhiatal proximal gastrectomy is
      safe for patients with adenocarcinoma of the esophagogastric junction and the
      short-term clinical outcomes are favorable.

PMID- 22990921
TI  - [Surgical treatment of Siewert II adenocarcinoma of the esophagogastric
      junction].
AB  - OBJECTIVE: To explore the outcomes after surgical treatment of esophagogastric
      junction carcinoma (EGJC). METHODS: One hundred and eighty-five patients with
      EGJC undergoing surgery from October 2000 to September 2006 at the Cancer
      Hospital of Shantou University were reviewed retrospectively. The clinical
      outcomes were compared between transthoracic and transabdominal approach.
      RESULTS: Of the 185 patients, 133 underwent operation via transthoracic approach
      and 52 via transabdominal approach. The postoperative complication rates were
      10.5%(14/133) and 11.5%(6/52) and the 1-, 3-, 5-year overall survival rates were
      83.9%, 44.5%, 32.9% and 86.0%, 38.0%, 30.0% in transthoracic and transabdominal
      groups respectively, and the difference were not statistically significant (both
      P>0.05). CONCLUSION: Surgical approach should be individualized for EGCJ.

PMID- 22990922
TI  - [Comparative study of endoscopic mucous resection with transparent cap and
      endoscopic multi-band mucosectomy for early esophageal cancer and precancerous
      lesion].
AB  - OBJECTIVE: To evaluate the efficacy and safety of endoscopic mucous resection
      with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the
      treatment of early esophageal cancer and precancerous lesion. METHODS: A
      retrospective study was performed to review 30 EMR-Cap cases from December 2008
      to December 2009 and 32 MBM cases from January 2010 to January 2011 of early
      esophageal cancer and precancerous lesions. The differences between these two
      techniques in efficacy, safety, and cost were compared. RESULTS: In EMR-Cap
      group, the median resection time was 26(10-56) min and median procedure time was
      43(22-81) min, significantly longer than those in MBM group [10(7-18) min and
      32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant
      differences between the two groups in total thickness and depth of resected
      lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than
      that of MBM group [(5466+/-354) vs. (4014+/-368) RMB, P=0.008)]. CONCLUSIONS: EMR
      Cap and MBM are minimally invasive, safe and effective methods in the treatment
      of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM
      is simple with shorter treatment time and lower cost.

PMID- 22990923
TI  - [Analysis of learning process of video-assisted minimally invasive esophagectomy
      for thoracic esophageal carcinoma].
AB  - OBJECTIVE: To evaluate the learning process of video-assisted minimally invasive
      esophagectomy (MIE). METHODS: One hundred consecutive patients with thoracic
      esophageal carcinoma were treated by a same team of surgeons, and were divided
      into 3 groups in chronological order. The former two groups both consisted of 25
      patients with thoracoscopy plus laparotomy. The remaining 50 patients were
      enrolled in the third group with thoracoscopy plus laparoscopy.
      Clinicopathological data including operative time, blood loss, protection of
      normal structures, complications, length of ICU stay, postoperative stay, and
      lymph nodes harvest, were collected and compared between groups. RESULTS:
      Procedures were accomplished successfully in 96 patients. Only 4 cases were
      converted to open thoracotomy and none to laparotomy. The median operative time
      was 310 min and blood loss was 200 ml. The median number of lymph node harvest
      was 22. The overall complication rate was 50%. Comparison of first two groups
      revealed that significant differences existed in the preservation rate of arch of
      azygos vein (P=0.010), bronchial vessels (P=0.038), and exposure rate of thoracic
      part of left recurrent laryngeal nerve( P=0.048). Comparison of the former and
      latter 50 patients revealed that significant differences existed in thoracic
      operative time (P<0.001), blood loss (P=0.025), preservation rate of arch of
      azygos vein (P=0.001) and bronchial vessels (P<0.001), the number of lymph node
      harvest in thoracoscopy (P=0.022) and in left recurrent laryngeal nerve chain
      (P<0.001), and exposure rate of initiate part of left recurrent laryngeal nerve
      (P=0.002). CONCLUSION: The learning curve of MIE is long and beginners should
      proceed step by step.

PMID- 22990924
TI  - [Comparative study of perioperative complications and lymphadenectomy between
      minimally invasive esophagectomy and open procedure].
AB  - OBJECTIVE: To analyze the differences in perioperative morbidity and lymph node
      dissection between minimally invasive esophageal carcinoma resection and open
      procedure. METHODS: From January to December 2011, 72 patients with esophageal
      cancer underwent surgery. Thirty-four patients underwent video-assisted
      esophagectomy, and 38 underwent open procedure. In the minimally invasive group,
      there were 7 thoraco-laparoscopic cases, 16 thoracoscopic cases, and 11
      laparoscopic cases. RESULTS: The early cases (T1-T2) were more common in the
      minimally invasive group than that in the open group [79.4%(27/34) vs.
      55.3%(21/38), P<0.05]. The complication rate was 41.2%(11/34) in the open group
      and 42.1%(16/38) in the minimally invasive group, and the difference was not
      statistically significant (P>0.05). However, the functional complication in
      minimally invasive group was significantly lower than that in open group
      [2.9%(1/34) vs. 28.9%(11/38), P<0.01], while technical complications (anastomotic
      leak and recurrent laryngeal nerve injury) were significantly more common( 38.2%
      vs. 10.5%, P<0.05). Lymph node group number in minimally invasive group was
      comparable with the open group (9.1 vs. 11.2, P>0.05), but the number of node in
      minimally invasive group was significantly lower (13.5+/-5.9 vs. 17.8+/-5.2,
      P<0.05). When stratified by time period, early 17 cases were associated with
      similar technical complication rate with the late 17 cases (P>0.05), while
      thoracic lymph node group number, number of node, and positive node were improved
      in the late phase (all P>0.05). CONCLUSIONS: Minimally invasive esophagectomy
      reduces functional morbidity, while technical complication including anastomotic
      leak and recurrent laryngeal nerve injury may be increased. Endoscopic lymph node
      dissection may be comparable to open surgery.

PMID- 22990926
TI  - [Thoraco-laparoscopic esophagectomy with two-field lymph node dissection for
      esophageal carcinoma: report of 150 cases].
AB  - OBJECTIVE: To summarize early experience in combined thoraco-laparoscopic
      esophagectomy with two-field lymph node dissection for esophageal carcinoma.
      METHODS: A total of 150 patients with thoracic esophageal cancer who underwent
      combined thoracoscopic and laparoscopic esophagectomy in Union Hospital, Fujan
      Medical University, were enrolled in this study. RESULTS: Locations of the tumors
      included upper esophagus (n=14), middle esophagus (n=95), and lower esophagus
      (n=41). Pathological type showed squamous cell cancer (n=142) and other types of
      cancer (n=8). There was no intraoperative death. Conversion to open thoracotomy
      was required in 6 patients and conversion to open laparotomy in 2 patients. The
      average total operative time was( 258+/-45) min. The average operative
      thoracoscopic time was (140+/-33) min. The average time for gastric mobilization
      and neck esophagogastric anastomosis was (119+/-28) min. The average blood loss
      during the procedure was (207+/-130) ml. The average number of harvested lymph
      node with the specimen was 23.3+/-8.2. The tumor staging included stage I (n=39),
      II (n=58) and III (n=53). Postoperative complications occurred in 48(32%)
      patients including pneumonia (n=17), recurrent laryngeal injury (n=13),
      anastomotic leak (n=9), arrhythmias (n=9), chyle chest (n=5), delayed gastric
      emptying (n=5), ileus (n=2), volvulus (n=1), and thrombocytopenia (n=1). Two
      patients died postoperatively due to respiratory failure resulting from
      pneumonia. CONCLUSION: Thoraco-laparoscopic two-field lymph node dissection of
      esophageal cancer is a feasible minimally invasive approach.

PMID- 22990925
TI  - [Evaluation of safety of video-assisted thoracoscopic esophagectomy for
      esophageal carcinoma].
AB  - OBJECTIVE: To explore the safety of video-assisted thoracoscopic esophagectomy
      for esophageal carcinoma. METHODS: From January 2005 to March 2012, 260 patients
      with esophageal carcinoma received thoracoscopic esophagectomy (TE group), while
      322 patients underwent conventional open esophagectomy (OE group). Operative
      procedures, perioperative complications, reoperation, readmission to intensive
      care unit (ICU), and perioperative mortality were compared between the two
      groups. RESULTS: Compared with OE group, TE group possessed less thoracic
      operative time [(105+/-30) min vs. (112+/-41) min, P=0.000], less blood loss
      [(95+/-48) ml vs. (107+/-44) ml, P=0.002], shorter postoperative hospital stay
      [(14.3+/-7.5) d vs. (16.9+/-9.5) d, P=0.000] and more lymph node harvest from
      thorax [(13.5+/-5.0) vs. (11.6+/-4.7), P=0.000]. The total perioperative
      complication rate was lower in TE group than that of OE group (34.6% vs. 45.0%,
      P=0.011), as well as perioperative mortality (0.8% vs. 3.4%, P=0.032). Lower rate
      of readmission to ICU (5.4% vs. 10.6%, P=0.024) was found in the TE group as
      compared to the OE group, while the reoperation rate was comparable (1.5% vs.
      2.5%, P=0.425). CONCLUSION: Thoracoscopic esophagectomy is advantageous than open
      procedure in terms of surgical safety.

PMID- 22990927
TI  - [Minimally invasive esophagectomy for esophageal carcinoma: clinical analysis of
      160 cases].
AB  - OBJECTIVE: To explore the feasibility, safety and clinical application value of
      minimally invasive esophagectomy (MIE). METHODS: Clinical data of 160 patients
      undergoing minimally invasive approach in the West China Hospital of Sichuan
      University between February 2008 and December 2011 were analyzed retrospectively.
      RESULTS: There were 140 males and 20 females with a mean age of 59.6 years.
      Approaches to esophagectomy were thoracoscopic and laparoscopic esophagectomy
      (n=139), thoracoscopic and mediastinoscopic esophagectomy (n=3), laparoscopic
      assisted Ivor Lewis resection (n=15), thoraco-laparoscopic Ivor Lewis resection
      (n=3). The mean operative time was 364 (range 230-780) min and the mean blood
      loss was 286.2 (range 20 to 4000) ml. The tumor free resection margins (R0) were
      completely in 152 cases (95.0%). The mean lymph node harvested was 19.4 (range 6
      39). There were 11 (6.9%) cases converted to open operation including 9
      thoracotomy and 2 laparotomy. The intraoperative complication rate was 11.3%
      (18/160). The average length of intensive care unit (ICU) stay was 22.1(range 0
      to 430) h and the average length of postoperative hospital stay was 13.1 (range 7
      93 d). Postoperative complication occurred in 34.4% of patients. The 30-day
      mortality was 1.2% (2/160) and the overall mortality was 2.5% (4/160).
      CONCLUSION: MIE is technically feasible and safe for the treatment of esophageal
      carcinoma, which provides good or even better outcomes than open approach.

PMID- 22990928
TI  - [Comparison of thoraco-laparoscopic and open three-field subtotal esophagectomy
      for esophageal cancer].
AB  - OBJECTIVE: To evaluate the safety and efficacy of thoraco-laparoscopic subtotal
      esophagectomy in the treatment of esophageal cancer. METHODS: Clinical data of 98
      patients with esophageal cancer who underwent thoraco-laparoscopic subtotal
      esophagectomy from March 2009 to October 2011 were retrospectively analyzed. One
      hundred and five patients were served as controls who underwent open three-field
      subtotal esophagectomy in the same period. RESULTS: There were significant
      differences between thoraco-laparoscopic and open three-field subtotal
      esophagectomy in blood loss [(85.1+/-32.8) ml vs. (215.5+/-60.6) ml], length of
      stay [(12.7+/-3.5) d vs. (16.9+/-4.5) d]), pneumonia (4.1% vs. 12.4%, P<0.05),
      atelectasis (3.1% vs. 10.5%, P<0.05), pleural effusion (3.1% vs. 10.5%, P<0.05),
      acute respiratory distress (1.0% vs. 7.6%, P<0.05) and arrhythmia (4.1% vs.
      12.4%, P<0.05). No significant differences were observed in the number of lymph
      node harvested, operative time, anastomotic leak, thoracic abscess, chyle chest,
      re-laparotomy, re-thoracotomy, vocal cord paralysis, renal failure, gastric
      emptying, and mortality (all P>0.05). CONCLUSION: Thoraco-laparoscopic subtotal
      esophagectomy is technically feasible and safe and is associated with less blood
      loss, less cardiopulmonary complication, and shorter hospital stay.

PMID- 22990929
TI  - [Neoadjuvant chemoradiotherapy followed by combined thoracoscopic and
      laparoscopic esophagectomy in the treatment of locally advanced esophageal
      carcinoma].
AB  - OBJECTIVE: To investigate the feasibility and efficacy of neoadjuvant
      chemoradiotherapy followed by combined thoracoscopic and laparoscopic
      esophagectomy (CTLE) in the treatment of advanced esophageal carcinoma. METHODS:
      From June 2011 to February 2012, 11 patients with locally advanced esophageal
      carcinoma underwent neoadjuvant chemoradiotherapy followed by CTLE (clinical
      stage IIB-IIIA). NP (vinorelbine pin and cisplatin) or TP (program paclitaxel-pin
      and cisplatin) were applied as preoperative chemotherapy. During the same period,
      conventional fractionated radiotherapy was used with the radiation dose of 40
      Gy/20 F. At four to six weeks after CRT, 11 patients received three-incision
      CTLE. RESULTS: During chemoradiation, 9 patients developed bone marrow
      suppression. The interval between completion of chemoradiation and surgery was
      (49.6+/-15.4) d. Intraoperative findings revealed local fibrosis in one patient
      (75 days after chemoradiation) while operative difficulty was not increased in
      the remaining 10 patients. Compared to 15 patients who received surgery alone,
      operative time was shorter [(242.3+/-27.0) min vs.(280.5+/-27.2) min, P=0.002]
      and intraoperative blood loss was less [(168.2+/-95.6) ml vs. (244.5+/-84.8) ml,
      P=0.042], the number of removal lymph nodes was similar [(19.5+/-5.8) vs. (20.5+/
      7.1), P=0.683], postoperative hospital stay was prolonged [(18.9+/-10.3) d vs.
      (12.5+/-4.6) d, P=0.020]. The postoperative complication rate was 36.4% including
      cervical anastomotic leak with pulmonary infection (n=1), cervical anastomotic
      fistula and hoarseness (n=1), pulmonary infection with pleural effusion (n=2).
      Follow up ranged from 1 to 9 months, and no recurrence was found. CONCLUSION: The
      neoadjuvant chemoradiotherapy followed by combined thoracoscopic and laparoscopic
      esophagectomy in the treatment of locally advanced esophageal carcinoma is safe,
      feasible, and the short-term outcomes are favorable.

PMID- 22990930
TI  - [Clinical application of minimally invasive esophagectomy for esophageal
      carcinoma].
AB  - OBJECTIVE: To investigate the feasibility and safety of minimally invasive
      esophagectomy (MIE) for esophageal carcinoma. METHODS: Clinical data of 298
      esophageal carcinoma cases who were treated by MIE in the Fujian Provincial
      Cancer Hospital from June 2008 to April 2012 were retrospectively reviewed.
      RESULTS: All the patients underwent MIE successfully except one conversion to
      open surgery. The mean operative time was (242.3+/-58.7) min. The postoperative
      length of hospital stay was (17.4+/-9.8) d. The number of harvested lymph nodes
      of total, the mediastinum, the abdomen and the cervix was 27.5+/-12.2, 10.7+/
      5.7, 13.3+/-7.8, and 7.7+/-8.1, respectively. Postoperative complication rate was
      29.9%, including pneumonia (n=41), recurrent laryngeal nerve injury (n=25),
      anastomotic leak (n=9), wound infection (n=7), and others (n=7). After follow up
      of 2 to 47 months, 3 patients were found to develop anastomotic stricture. There
      were no recurrence, metastasis, or death. CONCLUSION: Minimally invasive
      esophagectomy is a safe, feasible, effective and minimally invasive surgical
      technique.

PMID- 22990931
TI  - [Comparison of the short-term outcomes of patients with esophageal cancer after
      subtotal esophagectomy via thoracoscopy in left lateral position and in prone
      position].
AB  - OBJECTIVE: To compare the short-term outcomes in patients with esophageal cancer
      after subtotal esophagectomy via thoracoscopy in prone position and in left
      lateral position. METHODS: Between September 2008 and September 2010, thoraco
      laparoscopic esophagectomy (TLE) with thoracoscopic mobilization of the esophagus
      and mediastinal esophagectomy was performed in 41 patients in prone position
      (group A) and other 41 patients (group B) performed by the same surgeon in left
      lateral position. RESULTS: Preoperatively, the endoscopic location of the tumor
      was in the upper third in 5 cases (2 vs. 3), the middle third in 21 cases (12 vs.
      9), and the lower third in 56 cases (27 vs. 29). The median operative time was
      230 (range 170-310) min in group A and 280 (range 190-380) min in group B
      (P=0.04). The median intraoperative blood loss was 275 (range 100-320) ml in
      group A and 360 (range 120-670) ml in group B (P=0.09). The median number of
      lymph nodes dissected was 8.4 (range 4-23) in group A and 6.9 (range 6-21) in
      group B (P=0.03). The postoperative complications totaled 6 (14.6%) in group A
      and 8 (17.1%) in group B (P=0.44). After a median follow-up period of 15.7 (range
      2-28) months for group A and 16.3 (range 3-31) months for group B, 19 patients in
      group A died and 21 patients in group B. CONCLUSIONS: For esophageal cancer under
      T3N1M0, surgical outcomes are similar between prone thoracoscopic esophageal
      mobilization and left lateral position. Prone position may be associated with
      better lymph node dissection.

PMID- 22990932
TI  - [Preliminary study on gastric tube esophagoplasty for corrosive strictures of the
      esophagus in children].
AB  - OBJECTIVE: To study the clinical value of gastric tube esophagoplasty for
      complicated corrosive stricture of the esophagus in children. METHODS: A
      retrospective analysis was performed to study 7 patients with complicated
      corrosive stricture of the esophagus who were treated with gastric tube
      esophagoplasty via retrosternal route between March 2010 and October 2011.
      RESULTS: Three patients had a stricture longer than 2.5 cm, and 4 patients had
      more than one stricture. All the operations went well. The average time for
      mechanical ventilation postoperatively was 6 hours. No patients showed
      insufficient ventilation after withdraw of ventilator. There was 1 patient
      developed anastomotic leak which was healed a week later. One patient had
      anastomotic leak with pyloric obstruction, and the leak was healed 3 weeks after
      intraoperative placement of duodenal feeding tube and pyloric obstruction became
      patent 4 weeks later. There were 2 patients developed anastomotic stricture and
      they resumed normal diet after balloon dilatation. The average follow-up duration
      was 10.5 months. The quality of life was improved and no other complications were
      found. CONCLUSION: Gastric tube esophagoplasty is a effective alternative for
      complicated corrosive stricture of the esophagus and the short-term outcomes are
      favorable.

PMID- 22990933
TI  - [Impact of early enteral nutrition on the intestinal motility of patients after
      esophagectomy].
AB  - OBJECTIVE: To assess the impact of early enteral nutrition (EN) on the intestinal
      motility of patients after esophagectomy. METHODS: Thirty-five consecutive
      patients undergoing esophagectomy for esophageal cancer by a single surgical team
      from the Peking University Cancer Hospital from June 2011 to July 2011 were
      enrolled. Patients were randomly divided into EN group (n=20) and parenteral
      nutrition group (control group, n=15) within 24 h after esophagectomy procedure.
      Bowel sound recovery time was monitored by auscultation, and the gastrointestinal
      tract symptoms were recorded. RESULTS: Bowel sound recovery time was (45.1+/
      20.3) h in the EN group, and was (56.7+/-17.0) h in the control group (P=0.082).
      Gastrointestinal symptoms such as nausea, abdominal distension, diarrhea occurred
      in 4 patients in EN group and 3 patients in control group and were alleviated by
      lowering infusion speed and more off-bed ambulation, and no significant
      difference was seen between the two groups (P=1.000). CONCLUSIONS: Early enteral
      nutrition in the patients after esophagectomy is safe and feasible. Early enteral
      nutrition does not delayed bowel function recovery or increase gastrointestinal
      symptoms.

PMID- 22990934
TI  - [Impact of previous abdominal operations on the outcome of laparoscopy-assisted
      radical total gastrectomy].
AB  - OBJECTIVE: To explore the impact of previous abdominal operations on the outcome
      of laparoscopy-assisted radical total gastrectomy (LATG). METHODS: Clinical data
      of 328 patients with gastric cancer who underwent LATG from January 2008 to
      December 2010 were analyzed retrospectively. Among the patients, 57 cases had
      previous abdominal surgeries (PAS group) and 271 cases had no previous abdominal
      surgeries (NPAS group). The intraoperative and postoperative parameters were
      compared, and risk factors associated with postoperative complications were
      analyzed using univariate and multivariate analysis. RESULTS: There was no
      significant difference between the two groups in the mean number of lymph nodes
      harvested (30.2+/-10.5 vs. 31.1+/-9.4, P>0.05). The operative time [(247.0+/
      60.5) min vs. (214.7+/-57.0) min, P<0.01] and the postoperative complication rate
      [21.1%(12/57) vs. 11.1%(30/271), P<0.05] were significantly different between the
      two groups. However, there were no differences in intraoperative blood loss,
      transfused patients, conversion, postoperative ambulation time, postoperative
      flatus passage time, resumption of liquid diet, removal of gastric tube, and
      postoperative hospital stay (all P>0.05). Multivariate logistic regression
      analysis showed that previous abdominal surgeries was not an independent risk
      factor associated with postoperative complication morbidity (P>0.05).
      CONCLUSIONS: LATG is feasible for gastric cancer patients who has previous
      abdominal surgeries. Previous abdominal surgery may prolong operative time but is
      not an independent risk factor associated with postoperative complication.

PMID- 22990935
TI  - [Laparoscopic versus open surgery for D2 gastrectomy in advanced gastric cancer].
AB  - OBJECTIVE: To investigate the safety and feasibility of laparoscopic D2
      gastrectomy for advanced gastric cancer. METHODS: The clinical data of 210 cases
      of laparoscopic gastrectomy and 180 cases of open gastrectomy for radical (D2)
      gastrectomy from May 2007 to Dec 2010 were analyzed retrospectively. RESULTS: A
      total of 206 cases underwent laparoscopic-assisted surgery with 4 conversions.
      Compared to the open group, the laparoscopic group was associated with less
      bleeding [(208+/-38) ml vs. (300+/-52) ml, P<0.05], quicker postoperative
      recovery of bowel function [(2.9+/-0.7) d vs. (3.9+/-1.8) d, P<0.05], shorter
      postoperative length of hospital stay[(12.8+/-6.2) d vs. (15.6+/-6.8) d, P<0.05],
      longer operative time [(258+/-42) min vs. (193+/-30) min, P<0.05]. The number of
      lymph node harvested was 20.5+/-1.9 in the laparoscopic group and 25.8+/-1.5 in
      the open group, and the postoperative complication rate was 8.1% (17/201) vs.
      8.5% (15/180), and differences were not statistically significant (both P>0.05).
      The recurrence rate was 2.9% (6/210) and 2.8% (5/180), and the 3-year overall
      survival rate was 35.6% and 37.8%, the differences were not statistically
      significant (both P>0.05). CONCLUSIONS: Laparoscopic radical gastrectomy for
      gastric cancer is safe and effective, which can reach the same range of lymph
      node dissection as open gastric cancer surgery and similar survival rate.

PMID- 22990936
TI  - [Gastric carcinoma in a 12-year-old girl: a case report and literature review].
AB  - OBJECTIVE: To report the diagnosis and treatment experience of pediatric gastric
      cancer. METHODS: Clinicopathological data of a girl with gastric carcinoma in
      December 2011 was analyzed retrospectively. The literatures were reviewed. The
      disease onset, clinical manifestations, treatment, and prognosis of the patient
      with gastric carcinoma were studied. RESULTS: The patient was a 12-year-old girl,
      and the tumor was located in greater curvature. The girl underwent laparoscopy
      assisted radical total gastrectomy (D2). Pathological examination showed gastric
      ulcerative signet-ring cell cancer (pT4N0M0, stage II b). The outcome at the
      recent follow up was satisfactory. Literature review demonstrated 15 cases of
      pediatric gastric carcinoma, of whom 7 were boys and 8 girls. Their average age
      was 12.7 years (2.5-17.8 years). Tumor locations included cardia (n=5), gastric
      body (n=1), gastric antrum or stomach corner (n=4), gastric antrum and gastric
      body (n=1), and unknown (n=4). Histology showed signet-ring cell cancer in 4
      patients, poorly differentiated in 6, moderate to poorly differentiated and
      moderate differentiated adenocarcinoma in 2. Operation was performed in 11 cases
      and perioperative chemotherapy in 8 cases. Nine patients had follow-up. Four
      patients died within 6 months and other 4 patients survived for 6 months to one
      year. The survival time of one patient who underwent radical surgery and
      perioperative chemotherapy was 102 months. CONCLUSIONS: Pediatric gastric
      carcinoma is extremely rare. It is highly malignant and associated with poor
      prognosis. Radical surgery is the most important treatment. Perioperative
      chemotherapy may improve the prognosis.

PMID- 22990937
TI  - [Use of laparoscope complete mesocolic excision in the surgical treatment of
      right colon cancer].
AB  - OBJECTIVE: To investigate the efficacy of laparoscope complete mesocolic excision
      (CME) for right colon cancer. METHODS: The clinical data of 49 cases of right
      colon cancer without metastasis and intestinal obstruction who underwent elective
      laparoscope CME by the same group of surgeons between October 2009 and June 2011
      at the First Hospital of Jilin University were analyzed retrospectively. RESULTS:
      Among the 49 cases with CME, the median number of total lymph node retrieved was
      22. The positive rate of lymph node in patients with stage III disease was 16.3%.
      The median operative time of all the cases was 145 min. The mean intraoperative
      blood loss was 75 ml. The median time to flatus passage and defecation was 3 days
      and 6 days respectively. The median hospital stay was 12 days. The overall
      postoperative complication rate was 12.2% (6/49). CONCLUSION: Laparoscope
      complete mesocolic excision for right colon cancer is safe and feasible.

PMID- 22990938
TI  - [Research progress of prognostic protein biomarkers associated with esophagus
      squamous cell carcinoma].
AB  - Esophageal cancer (EC) is one of the common malignant tumors in China.
      Esophagectomy based on multi-disciplinary principle improves the quality of life
      and survival of esophageal cancer patients, but a lot of patients will suffer
      recurrence or metastasis after surgery. TNM stage is the most important factor
      which affects the prognosis of patients with esophageal cancer. Besides, there
      are other prognostic factors, such as abnormal expression of the proteins.
      Exploration of these proteins may provide new clues to improve prognosis in
      esophageal squamous cell cancer (ESCC). We reviewed the literatures related to
      abnormal protein expression in ESCC, and tried to elucidate the prognostic value
      and potential clinical application of these proteins in ESCC.

PMID- 22990939
TI  - A population-based study of metastatic colorectal cancer in individuals aged >=
      80 years: findings from the South Australian Clinical Registry for Metastatic
      Colorectal Cancer.
AB  - BACKGROUND: Life expectancy is increasing, and more patients are presenting with
      cancer at an advanced age (>=80 years). Optimal management for this group of
      patients has not been well defined. METHODS: The South Australian Clinical
      Registry for Metastatic Colorectal Cancer (mCRC) collects data on all patients
      diagnosed since February 2006 in South Australia. The authors examined cancer
      characteristics, treatments administered, and outcomes for patients aged >=80
      years compared with patients aged <80 years. RESULTS: Data from 2314 patients
      were evaluable, and 29.2% of these patients were aged >=80 years. The majority
      had moderately differentiated tumors. Poorly differentiated tumors were reported
      in fewer patients aged >=80 years (20.1% vs 26.1%; P < .005). Overall, 28.1% of
      patients aged >=80 years received chemotherapy, and 74.2% received single-agent
      fluoropyrimidines as first-line treatment. By comparison, 68.2% of patients aged
      <80 years received chemotherapy, 74.3% received combination chemotherapy, and
      25.7% received single-agent fluoropyrimidine as first-line treatment. No
      treatment was received by 38.2% of patients aged >=80 years compared with 11.4%
      of those aged <80 years. Participation in clinical trials was lower in patients
      aged >=80 years (2% vs 13%). The median survival was worse for patients aged >=80
      years (8.2 months vs 19.2 months; P < .001), and the median survival of patients
      who received chemotherapy was 19.0 months for those aged >=80 years and 22.3
      months for those aged <80 years (P = .139). Patients who did not receive
      treatment had a poor median survival regardless of age (2.6 months for patients
      aged >=80 years vs 2.7 months for patients aged <80 years). CONCLUSIONS: Patients
      aged >=80 years were less likely to receive intervention for their metastatic
      colorectal cancer and had poorer survival. The survival of selected patients aged
      >=80 years who received chemotherapy was similar to the survival of those aged
      <80 years despite the receipt of single-agent therapy. Patients aged >=80 years
      with metastatic colorectal cancer are less likely to receive intervention for
      their disease and have poorer survival. Survival for selected patients aged >=80
      years who receive chemotherapy is similar to the survival of patients aged <80
      years despite the receipt of single-agent therapy.

PMID- 22990940
TI  - Evidence for the Two-State-Two-Mode model in retinal protonated Schiff-bases from
      pump degenerate four-wave-mixing experiments.
AB  - We apply spectrally-resolved pump degenerate four-wave-mixing for the
      characterization of excited state low-frequency vibrational coherences during the
      initial events in excited state double-bond isomerization of retinal protonated
      Schiff-bases. A set of low-frequency coherences in the energetic range of 100-350
      cm(-1) appears in the dynamics already for very early delays after initial
      excitation (<100 fs). The modulations are rapidly damped (<800 fs) and detectable
      only in a certain time window after initial excitation (<0.6 ps). Following the
      initial relaxation process, which leads the molecule to a stationary point in the
      S(1) state, it is not possible to re-excite the coherences in the excited state.
      Based on our observations, we conclude that the activation of the coherences is
      only possible to occur in a well-defined region of the excited state potential
      near the Franck-Condon region. Our results give direct experimental indication
      for the validity of the "Two-State-Two-Mode model", frequently applied for the
      interpretation of retinal isomerization dynamics.

PMID- 22990944
TI  - Persistence, bioaccumulation, and toxicity of halogen-free flame retardants.
AB  - Polymers are synthetic organic materials having a high carbon and hydrogen
      content, which make them readily combustible. Polymers have many indoor uses and
      their flammability makes them a fire hazard. Therefore, flame retardants (FRs)
      are incorporated into these materials as a safety measure. Brominated flame
      retardants (BFRs), which accounted for about 21% of the total world market of
      FRs, have several unintended negative effects on the environment and human
      health. Hence, there is growing interest in finding appropriate alternative
      halogen-free flame retardants (HFFRs). Many of these HFFRs are marketed already,
      although their environ- mental behavior and toxicological properties are often
      only known to a limited extent, and their potential impact on the environment
      cannot yet be properly assessed. Therefore, we undertook this review to make an
      inventory of the available data that exists (up to September 2011) on the
      physical-chemical properties, pro- duction volumes, persistence, bioaccumulation,
      and toxicity (PBT) of a selection of HFFRs that are potential replacements for
      BFRs in polymers. Large data gaps were identified for the physical-chemical and
      the PBT properties of the reviewed HFFRs. Because these HFFRs are currently on
      the market, there is an urgent need to fill these data gaps. Enhanced
      transparency of methodology and data are needed to reevaluate certain test
      results that appear contradictory, and, if this does not provide new insights,
      further research should be performed. TPP has been studied quite extensively and
      it is clearly persistent, bioaccumulative, and toxic. So far, RDP and BDP have
      demonstrated low to high ecotoxicity and persistence. The compounds ATH and ZB
      exerted high toxicity to some species and ALPI appeared to be persistent and has
      low to moderate reported ecotoxicity. DOPO and MPP may be persistent, but this
      view is based merely on one or two studies, clearly indicating a lack of
      information. Many degradation studies have been performed on PER and show low
      persistence, with a few exceptions. Additionally, there is too l ittle
      information on the bioaccumulation potential of PER. APP mostly has low PBT
      properties; however, moderate ecotoxicity was reported in two studies. Mg(OH)2,
      ZHS, and ZS do not show such remarkably high bioaccumulation or toxicity, but
      large data gaps exist for these compounds also. Nevertheless, we consider the
      latter compounds to be the most promising among alternative HFFRs. To assess
      whether the presently reviewed HFFRs are truly suitable alternatives, each
      compound should be examined individually by comparing its PBT values with those
      of the relevant halogenated flame retardant. Until more data are available, it
      remains impossible to accurately evaluate the risk of each of these compounds,
      including the ones that are already extensively marketed.

PMID- 22990942
TI  - Lithium and GSK3-beta promoter gene variants influence white matter
      microstructure in bipolar disorder.
AB  - Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits
      glycogen synthase kinase 3-beta (GSK3-beta). The less active GSK3-beta promoter
      gene variants have been associated with less detrimental clinical features of BD.
      GSK3-beta gene variants and lithium can influence brain gray matter structure in
      psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter
      (WM) integrity showed widespred disruption of WM structure in BD. In a sample of
      70 patients affected by a major depressive episode in course of BD, we
      investigated the effect of ongoing long-term lithium treatment and GSK3-beta
      promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based
      spatial statistics with threshold-free cluster enhancement. We report that the
      less active GSK3-beta rs334558*C gene-promoter variants, and the long-term
      administration of the GSK3-beta inhibitor lithium, were associated with increases
      of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including
      corpus callosum, forceps major, anterior and posterior cingulum bundle
      (bilaterally including its hippocampal part), left superior and inferior
      longitudinal fasciculus, left inferior fronto-occipital fasciculus, left
      posterior thalamic radiation, bilateral superior and posterior corona radiata,
      and bilateral corticospinal tract. AD reflects the integrity of axons and myelin
      sheaths. We suggest that GSK3-beta inhibition and lithium could counteract the
      detrimental influences of BD on WM structure, with specific benefits resulting
      from effects on specific WM tracts contributing to the functional integrity of
      the brain and involving interhemispheric, limbic, and large frontal, parietal,
      and fronto-occipital connections.

PMID- 22990945
TI  - Radiation exposure and adverse health effects of interventional cardiology staff.
AB  - To the best of our knowledge, this chapter constitutes the first systematic
      review of radiation exposure to eyes, thyroid, and hands for Interventional
      Cardiology (IC) staff. We have concluded from our review that these anatomical
      locations are likely to be exposed to radiation as a result of the limited use of
      personal protective equipment (PPE) among IC staff as shown in Fig. 8. Our review
      also reveals that, with the exception of three eye exposure cases, the annual
      radiation dose to eyes, thyroid, and hands among IC staff was within recommended
      levels and limits. The As Low As Reasonably Achievable (ALARA) limit was not
      achieved in three cases for fingers/hands and four cases for eyes. However, an
      increased incidence of cataracts were reported for IC staff, and this gives rise
      to the concern that low-dose or unnoticed exposures may increase the risk of
      developing cataracts among cardiology staff. Clearly, the formation of cataracts
      among IC staff may be an issue and should be studied in more depth. Our review
      also disclosed that the two groups who receive excessive radiation doses (i.e.,
      exceed the recommended limit) are physicians-in-training and junior staff
      physicians who work in cardiac catheterization laboratories. In particular, more
      attention should be given to assessing the effects of radiation exposure among IC
      staff who work in the Asia Pacific countries, because our review indicates that
      the number of IC procedures performed by IC staff in these countries is higher
      than for other continents. There is a huge demand for procedures conducted by IC
      staff in the Asia-Pacific area, for both treating patients and consulting with
      specialists. Our review also disclosed that recommended limits for per-procedure
      radiation doses are needed for IC staff. We recommend that such limits be
      established by the appropriate national and international agencies that are
      responsible for occupational radiation exposure. Although our review indicates
      that the current precautions against LDR exposure for IC staff are adequate in
      most cases, we are concerned about the relatively high incidence of cataracts
      reported to exist among IC staff. Therefore, we believe that there is a need for
      a strict implementation of radiation safety practices in cardiology laboratories
      and associated workplaces that utilize radiation. The action that is most
      important for protecting staff in the workplace against radiation exposure is the
      regular use of personal protective equipment or shielding. Working at a safe
      distance from instruments and assuring that such instruments are in the proper
      position are other techniques that can reduce the radiation dose received by IC
      staff.

PMID- 22990943
TI  - Candidate genes expression profile associated with antidepressants response in
      the GENDEP study: differentiating between baseline 'predictors' and longitudinal
      'targets'.
AB  - To improve the 'personalized-medicine' approach to the treatment of depression,
      we need to identify biomarkers that, assessed before starting treatment, predict
      future response to antidepressants ('predictors'), as well as biomarkers that are
      targeted by antidepressants and change longitudinally during the treatment
      ('targets'). In this study, we tested the leukocyte mRNA expression levels of
      genes belonging to glucocorticoid receptor (GR) function (FKBP-4, FKBP-5, and
      GR), inflammation (interleukin (IL)-1alpha, IL-1beta, IL-4, IL-6, IL-7, IL-8, IL
      10, macrophage inhibiting factor (MIF), and tumor necrosis factor (TNF)-alpha),
      and neuroplasticity (brain-derived neurotrophic factor (BDNF), p11 and VGF), in
      healthy controls (n=34) and depressed patients (n=74), before and after 8 weeks
      of treatment with escitalopram or nortriptyline, as part of the Genome-based
      Therapeutic Drugs for Depression study. Non-responders had higher baseline mRNA
      levels of IL-1beta (+33%), MIF (+48%), and TNF-alpha (+39%). Antidepressants
      reduced the levels of IL-1beta (-6%) and MIF (-24%), and increased the levels of
      GR (+5%) and p11 (+8%), but these changes were not associated with treatment
      response. In contrast, successful antidepressant response was associated with a
      reduction in the levels of IL-6 (-9%) and of FKBP5 (-11%), and with an increase
      in the levels of BDNF (+48%) and VGF (+20%)-that is, response was associated with
      changes in genes that did not predict, at the baseline, the response. Our
      findings indicate a dissociation between 'predictors' and 'targets' of
      antidepressant responders. Indeed, while higher levels of proinflammatory
      cytokines predict lack of future response to antidepressants, changes in
      inflammation associated with antidepressant response are not reflected by all
      cytokines at the same time. In contrast, modulation of the GR complex and of
      neuroplasticity is needed to observe a therapeutic antidepressant effect.

PMID- 22990946
TI  - Environmental fate and toxicology of methomyl.
AB  - The insecticide methomyl, an oxime carbamate, was first introduced in 1968 for
      broad spectrum control of several insect classes, including Lepidoptera,
      Hemiptera, Homoptera, Diptera, and Coleoptera. Like other carbamates, it inhibits
      AChE activity, resulting in nerve and/or tissue failure and possibly death.
      Considered highly toxic to insects (larval and adult stages), methomyl is thought
      to be metabolically degraded via mixed-function oxidase(s). Methomyl has both a
      low vapor pressure and Henry's law constant; hence, volatilization is not a major
      dissipation route from either water or moist or dry soils. Photolysis represents
      a minor dissipation pathway; however, under catalytic conditions, degradation via
      photolysis does occur. Methomyl possesses a moderate-to-high water solubility;
      thus hydrolysis, under alkaline conditions, represents a major degradation
      pathway. Methomyl has a low-to-moderate sorption capacity to soil. Although
      results may vary with soil type and organic matter content, methomyl is unlikely
      to persist in complex soils. Methomyl is more rapidly degraded by microbes, and
      bacterial species have been identified that are capable of using methomyl as a
      carbon and/or nitrogen source. The main degradation products of methomyl from
      both abiotic and biotic processes are methomyl oxime, acetonitrile, and CO2.
      Methomyl is moderately to highly toxic to fishes and very highly toxic to aquatic
      invertebrates. Methomyl is highly toxic orally to birds and mammals. Methomyl is
      classed as being highly toxic to humans via oral exposures, moderately toxic via
      inhalation, and slightly toxic via dermal exposure. At relatively high doses, it
      can be fatal to humans. Although methomyl has been widely used to treat field
      crops and has high water solubility, it has only infrequently been detected as a
      contaminant of water bodies in the USA. It is classified as a restricted-use
      insecticide because of its toxicity to multiple nontarget species. To prevent
      nontarget species toxicity or the possibility of contamination, as with all
      pesticides, great care should be taken when applying methomyl-containing products
      for agricultural, residential, or other uses.

PMID- 22990947
TI  - Recent advances in drinking water disinfection: successes and challenges.
AB  - Drinking water is the most important single source of human exposure to
      gastroenteric diseases, mainly as a result of the ingestion of microbial
      contaminated water. Waterborne microbial agents that pose a health risk to humans
      include enteropathogenic bacteria, viruses, and protozoa. Therefore, properly
      assessing whether these hazardous agents enter drinking water supplies, and if
      they do, whether they are disinfected adequately, are undoubtedly aspects
      critical to protecting public health. As new pathogens emerge, monitoring for
      relevant indicator microorganisms (e.g., process microbial indicators, fecal
      indicators, and index and model organisms) is crucial to ensuring drinking water
      safety. Another crucially important step to maintaining public health is
      implementing Water Safety Plans (WSPs), as is recommended by the current WHO
      Guidelines for Drinking Water Quality. Good WSPs include creating health-based
      targets that aim to reduce microbial risks and adverse health effects to which a
      population is exposed through drinking water. The use of disinfectants to
      inactivate microbial pathogens in drinking water has played a central role in
      reducing the incidence of waterborne diseases and is considered to be among the
      most successful interventions for preserving and promoting public health.
      Chlorine-based disinfectants are the most commonly used disinfectants and are
      cheap and easy to use. Free chlorine is an effective disinfectant for bacteria
      and viruses; however, it is not always effective against C. parvum and G.
      lamblia. Another limitation of using chlorination is that it produces
      disinfection by-products (DBPs), which pose potential health risks of their own.
      Currently, most drinking water regulations aggressively address DBP problems in
      public water distribution systems. The DBPs of most concern include the
      trihalomethanes (THMs), the haloacetic acids (HAAs), bromate, and chlorite.
      However, in the latest edition of the WHO Guidelines for Drinking Water Quality,
      it is recommended that water disinfection should never be compromised by
      attempting to control DBPs. The reason for this is that the risks of human
      illness and death from pathogens in drinking water are much greater than the
      risks from exposure to disinfectants and disinfection by-products. Nevertheless,
      if DBP levels exceed regulatory limits, strategies should focus on eliminating
      organic impurities that foster their formation, without compromising
      disinfection. As alternatives to chlorine, disinfectants such as chloramines,
      ozone, chlorine dioxide, and UV disinfection are gaining popularity. Chlorine and
      each of these disinfectants have individual advantage and disadvantage in terms
      of cost, efficacy-stability, ease of application, and nature of disinfectant by
      products (DBPs). Based on efficiency, ozone is the most efficient disinfectant
      for inactivating bacteria, viruses, and protozoa. In contrast, chloramines are
      the least efficient and are not recommended for use as primary disinfectants.
      Chloramines are favored for secondary water disinfection, because they react more
      slowly than chlorine and are more persistent in distribution systems. In
      addition, chloramines produce lower DBP levels than does chlorine, although
      microbial activity in the distribution system may produce nitrate from
      monochloramine, when it is used as a residual disinfectant, Achieving the
      required levels of water quality, particularly microbial inactivation levels,
      while minimizing DBP formation requires the application of proper risk and
      disinfection management protocols. In addition, the failure of conventional
      treatment processes to eliminate critical waterborne pathogens in drinking water
      demand that improved and/or new disinfection technologies be developed. Recent
      research has disclosed that nanotechnology may offer solutions in this area,
      through the use of nanosorbents, nanocatalysts, bioactive nanoparticles,
      nanostructured catalytic membranes, and nanoparticle-enhanced filtration.

PMID- 22990948
TI  - Safety of aspirin desensitization in patients with reported aspirin allergy and
      cardiovascular disease.
AB  - BACKGROUND: Aspirin (ASA) is the drug of choice in patients with coronary artery
      disease for primary and secondary prevention. This poses a problem for those
      patients reporting hypersensitivity to this drug or class of drugs. HYPOTHESIS:
      Desensitization to ASA may be carried out safely and effectively in patients with
      reported ASA or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity
      needing ASA for cardiac indications. Our 7-step protocol is one choice for a
      rapid desensitization protocol. METHODS: A retrospective chart review was
      conducted evaluating ASA desensitization in patients with reported ASA or NSAID
      hypersensitivity and a cardiac indication for ASA. RESULTS: In 160 evaluations
      over 15 years, 89 desensitizations were performed in both the inpatient and
      outpatient setting with only 16 reactions (18%). Eleven of these 16 patients
      (68.7%) were able to take daily ASA. Twenty-six desensitization procedures were
      performed with our 7-step rapid desensitization protocol in 10 inpatients and 16
      outpatients with 3 reactions (18.75% of reactions). Initial reaction to ASA
      involving angioedema and reacting to ASA within the past year increased the risk
      of having a reaction to desensitization. CONCLUSIONS: Desensitization may be
      safely performed in patients with reported ASA or NSAID hypersensitivity and a
      cardiac indication for ASA. Our 7-step rapid protocol may be used in both the
      inpatient and outpatient setting to desensitize these patients. Patients who had
      angioedema with ASA ingestion or a reaction to ASA within the past year are at
      higher risk for reaction during the desensitization protocol. The authors have no
      funding, financial relationships, or conflicts of interest to disclose.

PMID- 22990949
TI  - Remarkable differences between three evidence-based guidelines on management of
      obstructive sleep apnea-hypopnea syndrome.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to compare available guidelines
      for the diagnosis and treatment of patients with obstructive sleep apnea-hypopnea
      syndrome (OSAHS) regarding their content, conclusions on the available evidence,
      and recommendations. STUDY DESIGN: Literature review/systematic review. METHODS:
      We retrieved guidelines from Embase, PubMed, Web of Science, and Web sites of
      several health care improvement centers and with a Google Scholar search. We
      appraised the quality of selected guidelines according to the Appraisal of
      Guidelines for Research and Evaluation instrument. For similar clinical questions
      we compared the conclusions, the attached levels of evidence, and the references
      used. If differences were found, we checked search strategies, appraisal
      criteria, and publication date as possible sources for these differences.
      RESULTS: We selected the guidelines on diagnosis and treatment of OSAHS of the
      Scottish Scottish Intercollegiate Guidelines Network, the Dutch Institute for
      Healthcare Improvement, and the Institute for Clinical Systems Improvement in the
      United States for this comparison. For similar clinical questions these three
      guidelines showed conflicting conclusions (11%-18%), differences in attached
      levels of evidence (32%-62%), and remarkable discrepancies in cited studies. A
      plausible reason for these differences is the citation preference for articles
      from members of the guidelines workgroup and from their own country. Despite
      different publication dates, more recent guidelines fail to cite earlier
      published guidelines. CONCLUSIONS: Despite the generally accepted approach
      regarding the development of evidence-based guidelines, remarkable differences
      exist between guidelines from different countries on the same clinical subject.

PMID- 22990950
TI  - Randomized, controlled trial of multimodal shoulder injection or intravenous
      patient-controlled analgesia after arthroscopic rotator cuff repair.
AB  - PURPOSE: The aim of this study was to compare the effect of postoperative pain
      control and adverse effects of intravenous patient-controlled analgesia (IV PCA)
      and multimodal shoulder injection after arthroscopic rotator cuff repair.
      METHODS: Seventy patients scheduled for elective arthroscopic rotator cuff repair
      were prospectively randomized to receive either IV PCA or multimodal shoulder
      injections. Postoperative pain, nausea, vomiting, and other adverse effects were
      assessed at 2, 6, 12, 24, and 48 h after surgery. Use of rescue analgesics and
      antiemetics, level of satisfaction, and cost for both modalities were recorded.
      RESULTS: Pain was better controlled in the multimodal shoulder injection group at
      2 h postoperatively (P = 0.001). However, the use of additional analgesics was
      greater in the multimodal shoulder injection group during 12-48 h after surgery
      (P < 0.001). The incidence of nausea within 12-24 h after surgery in the
      multimodal shoulder injection group (5.7 %) was less significant compared with
      that in the IV PCA group (31.4 %, P = 0.012), but no difference in overall
      incidence of the use of rescue antiemetics was observed between the groups
      (n.s.). No differences in adverse effects were noted between the groups. Patient
      satisfaction also showed no differences (n.s.). Costs required for both
      modalities were $20.3 for the multimodal shoulder injection and $157.8 for the IV
      PCA. CONCLUSIONS: Multimodal shoulder injection is a safe and effective modality
      for management of pain after arthroscopic rotator cuff repair. Considering the
      expense and need of special devices for IV PCA, multimodal shoulder injection may
      be an effective and safe alternative to IV PCA for postoperative analgesia after
      arthroscopic rotator cuff repair.

PMID- 22990951
TI  - [Image-guided punch biopsy of the prostate].
AB  - The diagnnosis of prostate cancer is still being made on the basis of biopsy
      samples taken from the prostate. After the clinical introduction of transrectal
      sonography almost 30 years ago, this technique has undergone some innovations and
      changes in its methods of performance. Improvements in the transponder and
      ultrasound generator are not yet at an end. In the mean time supplementary
      methods to the B-mode imaging are available that enable improvements in the
      diagnosis. Apart from ultrasound-based procedure such as C-TRUS/ANNA, contrast
      medium-enhanced ultrasound (CEUS) and sonoelastography, MRI-based methods are now
      available to further improve the diagnosis of prostate cancer. It remains to be
      seen which method will establish itself in the future with the highest degree of
      diagnostic certainty and an appropriate cost-use relationship. From the
      urologist's point, however, diagnosis of and therapy for prostate cancer must
      remain in the domaine of urology.

PMID- 22990952
TI  - Electrochemical reduction of graphene oxide and its in situ
      spectroelectrochemical characterization.
AB  - The electrochemical properties of self-assembled films of graphene oxide (GO) on
      mercaptoethylamine (MEA) modified rough Au-surfaces were studied. The film
      deposition process on MEA primed gold was followed by surface plasmon resonance
      measurements and the film morphology on 3-aminopropyltriethoxysilane primed
      Si(100)-surface was studied by atomic force microscopy. The deposited few layer
      thick GO films on gold were electrochemically reduced by cyclic voltammetry
      simultaneously as the structural changes in the film were recorded by in situ
      vibrational spectroscopies. In situ surface enhanced infrared spectroscopy
      results indicate that the effect of the applied potential on the GO structure
      could be divided into two parts where the changes occurring at moderate negative
      potentials are mainly related to changes in the double layer at the film
      electrolyte interface and to hydrogen bonding of intercalated water between the
      GO sheets. At potentials more negative than -0.8 V vs. Ag/AgCl the reduction of
      GO starts to take place with concomitant conversion of the different functional
      groups of the film.

PMID- 22990953
TI  - Molecular cloning and biochemical analysis of tyrosinase from the crested ibis in
      China.
AB  - The crested ibis, one of the most endangered birds in the world, could benefit
      from research into its genetic diversity as a tool for conservation in the
      future. Tyrosinase is thought to play a major role in the production of common
      yellow to black melanins in birds. We have cloned and sequenced four exons of the
      crested ibis tyrosinase gene and discovered that the amino acid sequence has high
      similarity to zebra finch tyrosinase (93 %), followed by chicken (91 %) and quail
      (91 %). Some functional and structural domains in the crested ibis tyrosinase
      coding area were found to be conserved during evolution. Nine sequence variants
      were found in the partial coding sequence, one in exon 1 and eight in exon 4.
      Sequence variant 1 (SV1) shows intermediate polymorphism (0.25 < PIC < 0.5), and
      further study is needed to determine whether it can be used as a potential
      molecular marker in crested ibis artificial breeding programs.

PMID- 22990954
TI  - Molecular characterization and expression analysis of VSIG4 from the Asian yellow
      pond turtle, Mauremys mutica.
AB  - V-set and immunoglobulin domain-containing protein 4 (VSIG4), a member of the
      immunoglobulin superfamily, plays an important role in the immune system. This
      study isolated and characterized a cDNA encoding VSIG4 (MaVSIG4) from the Asian
      yellow pond turtle (Mauremys mutica). The MaVSIG4 cDNA is 1840 bp long and
      contains an open reading frame of 1,182 bp that encodes a polypeptide of 372
      amino acids. The genomic sequence of MaVSIG4 spans 7,682 bp, with six exons and
      five introns. The phylogenetic tree shows that MaVSIG4 is most closely related to
      Gallus gallus VSIG4. The expression analysis by real-time PCR reveals that
      MaVSIG4 is ubiquitously expressed in various healthy tissues, with a higher
      expression level in the liver. After immune stimulation, the expression level of
      MaVSIG4 sharply decreased in the liver, heart, and kidney at 12 h (P < 0.01).
      These results provide a basis for further study of the function of MaVSIG4 in the
      turtle's immune system.

PMID- 22990955
TI  - Decreasing activity and altered protein processing of human iduronate-2-sulfatase
      mutations demonstrated by expression in COS7 cells.

PMID- 22990956
TI  - A simple and affordable method of DNA extraction from fish scales for polymerase
      chain reaction.

PMID- 22990957
TI  - Morphological and morphometrical assessment of spermathecae of Aedes aegypti
      females.
AB  - The vectorial capacity of Aedes aegypti is directly influenced by its high
      reproductive output. Nevertheless, females are restricted to a single mating
      event, sufficient to acquire enough sperm to fertilize a lifetime supply of eggs.
      How Ae. aegypti is able to maintain viable spermatozoa remains a mystery. Male
      spermatozoa are stored within either of two spermathecae that in Ae. aegypti
      consist of one large and two smaller organs each. In addition, each organ is
      divided into reservoir, duct and glandular portions. Many aspects of the
      morphology of the spermatheca in virgin and inseminated Ae. aegypti were
      investigated here using a combination of light, confocal, electron and scanning
      microscopes, as well as histochemistry. The abundance of mitochondria and
      microvilli in spermathecal gland cells is suggestive of a secretory role and
      results obtained from periodic acid Schiff assays of cell apexes and lumens
      indicate that gland cells produce and secrete neutral polysaccharides probably
      related to maintenance of spermatozoa. These new data contribute to our
      understanding of gamete maintenance in the spermathecae of Ae. aegypti and to an
      improved general understanding of mosquito reproductive biology.

PMID- 22990958
TI  - Trypanosoma rangeli protein tyrosine phosphatase is associated with the
      parasite's flagellum.
AB  - Protein tyrosine phosphatases (PTPs) play an essential role in the regulation of
      cell differentiation in pathogenic trypanosomatids. In this study, we describe a
      PTP expressed by the non-pathogenic protozoan Trypanosoma rangeli (TrPTP2). The
      gene for this PTP is orthologous to the T. brucei TbPTP1 and Trypanosoma cruzi
      (TcPTP2) genes. Cloning and expression of the TrPTP2 and TcPTP2 proteins allowed
      anti-PTP2 monoclonal antibodies to be generated in BALB/c mice. When expressed by
      T. rangeli epimastigotes and trypomastigotes, native TrPTP2 is detected as a ~65
      kDa protein associated with the parasite's flagellum. Given that the flagellum is
      an important structure for cell differentiation in trypanosomatids, the presence
      of a protein responsible for tyrosine dephosphorylation in the T. rangeli
      flagellum could represent an interesting mechanism of regulation in this
      structure.

PMID- 22990959
TI  - Trichomonas vaginalis and Tritrichomonas foetus: interaction with fibroblasts and
      muscle cells - new insights into parasite-mediated host cell cytotoxicity.
AB  - Trichomonas vaginalis and Tritrichomonas foetus are parasitic, flagellated
      protists that inhabit the urogenital tract of humans and bovines, respectively.
      T. vaginalis causes the most prevalent non-viral sexually transmitted disease
      worldwide and has been associated with an increased risk for human
      immunodeficiency virus-1 infection in humans. Infections by T. foetus cause
      significant losses to the beef industry worldwide due to infertility and
      spontaneous abortion in cows. Several studies have shown a close association
      between trichomonads and the epithelium of the urogenital tract. However, little
      is known concerning the interaction of trichomonads with cells from deeper
      tissues, such as fibroblasts and muscle cells. Published parasite-host cell
      interaction studies have reported contradictory results regarding the ability of
      T. foetus and T. vaginalis to interact with and damage cells of different
      tissues. In this study, parasite-host cell interactions were examined by
      culturing primary human fibroblasts obtained from abdominal biopsies performed
      during plastic surgeries with trichomonads. In addition, mouse 3T3 fibroblasts,
      primary chick embryo myogenic cells and L6 muscle cells were also used as models
      of target cells. The parasite-host cell cultures were processed for scanning and
      transmission electron microscopy and were tested for cell viability and cell
      death. JC-1 staining, which measures mitochondrial membrane potential, was used
      to determine whether the parasites induced target cell damage. Terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labelling staining was used as
      an indicator of chromatin damage. The colorimetric crystal violet assay was
      performed to ana-lyse the cytotoxicity induced by the parasite. The results
      showed that T. foetus and T. vaginalis adhered to and were cytotoxic to both
      fibroblasts and muscle cells, indicating that trichomonas infection of the
      connective and muscle tissues is likely to occur; such infections could cause
      serious risks to the infected host.

PMID- 22990960
TI  - The infection of microvascular endothelial cells with ExoU-producing Pseudomonas
      aeruginosa triggers the release of von Willebrand factor and platelet adhesion.
AB  - An increased plasma concentration of von Willebrand factor (vWF) is detected in
      individuals with many infectious diseases and is accepted as a marker of
      endothelium activation and prothrombotic condition. To determine whether ExoU, a
      Pseudomonas aeruginosa cytotoxin with proinflammatory activity, enhances the
      release of vWF, microvascular endothelial cells were infected with the ExoU
      producing PA103 P. aeruginosa strain or an exoU-deficient mutant. Significantly
      increased vWF concentrations were detected in conditioned medium and
      subendothelial extracellular matrix from cultures infected with the wild-type
      bacteria, as determined by enzyme-linked immunoassays. PA103-infected cells also
      released higher concentrations of procoagulant microparticles containing
      increased amounts of membrane-associated vWF, as determined by flow cytometric
      analyses of cell culture supernatants. Both flow cytometry and confocal
      microscopy showed that increased amounts of vWF were associated with cytoplasmic
      membranes from cells infected with the ExoU-producing bacteria. PA103-infected
      cultures exposed to platelet suspensions exhibited increased percentages of cells
      with platelet adhesion. Because no modulation of the vWF mRNA levels was detected
      by reverse transcription-polymerase chain reaction assays in PA103-infected
      cells, ExoU is likely to have induced the release of vWF from cytoplasmic stores
      rather than vWF gene transcription. Such release is likely to modify the
      thromboresistance of microvascular endothelial cells.

PMID- 22990961
TI  - Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles
      between the clinical forms of visceral leishmaniasis.
AB  - It is not well established whether cytokine production differs in response to
      different clinical forms of visceral leishmaniasis (VL). In this work, we
      performed a cross-sectional study to investigate the plasma levels of cytokines
      [interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-2,
      IL-4, IL-10 and IL-12] involved in the pathogenesis of VL in 80 subjects from VL
      endemic areas, including subjects with active VL, subjects with asymptomatic
      infection, subjects with cured VL and uninfected controls. The patients were
      recruited by sampling from a referral hospital and by random selection from a
      population-based cohort study. The results showed significant differences in the
      plasma concentration of all cytokines between the groups (p < 0.05). Patients
      with the active disease had higher plasma levels of IL-10, IL-4, INF-gamma and
      TNF-alpha relative to the other groups and they produced more IL-12 than
      asymptomatic and cured subjects. Only the IL-2 concentration was higher in the
      asymptomatic and cured subjects relative to the patients with active disease (p <
      0.05). Our results suggest that these cytokines can be used as markers in
      epidemiological studies conducted in endemic areas to distinguish between
      different clinical forms of VL. However, their usefulness should be confirmed in
      investigations conducted in other endemic areas.

PMID- 22990962
TI  - Angiostrongylus cantonensis (Nematode: Metastrongyloidea) in molluscs from
      harbour areas in Brazil.
AB  - Angiostrongylus cantonensis is the most common aetiological agent of human
      eosinophilic meningoencephalitis. Following a report indicating the presence of
      this parasite in Brazil in 2007, the present study was undertaken to investigate
      the presence of A. cantonensis in the surrounding Brazilian port areas. In total,
      30 ports were investigated and the following molluscs were identified: Achatina
      fulica, Belocaulus sp., Bradybaena similaris sp., Cyclodontina sp., Helix sp.,
      Leptinaria sp., Melampus sp., Melanoides tuberculata, Phyllocaulis sp., Pomacea
      sp., Pseudoxychona sp., Rhinus sp., Sarasinula marginata, Streptaxis sp.,
      Subulina octona, Succinea sp., Tomigerus sp., Wayampia sp. and specimens
      belonging to Limacidae and Orthalicinae. Digestion and sedimentation processes
      were performed and the sediments were examined. DNA was extracted from the
      obtained larvae and the internal transcribed spacer region 2 was analysed by
      polymerase chain reaction-restriction fragment length polymorphism after
      digestion with the endonuclease ClaI. Of the 30 ports investigated in this study,
      11 contained molluscs infected with A. cantonensis larvae. The set of infected
      species consisted of S. octona, S. marginata, A. fulica and B. similaris. A total
      of 36.6% of the investigated ports were positive for A. cantonensis, indicating a
      wide distribution of this worm. It remains uncertain when and how A. cantonensis
      was introduced into South America.

PMID- 22990963
TI  - Metallo-beta-lactamase-production in meropenem-susceptible Pseudomonas aeruginosa
      isolates: risk for silent spread.
AB  - The aim of this study was to characterize two metallo-beta-lactamases (MBLs)
      producing Pseudomonas aeruginosa clinical isolates showing meropenem
      susceptibility. Antimicrobial susceptibility was assessed by automated testing
      and Clinical and Laboratory Standards Institute agar dilution method. MBL
      production was investigated by phenotypic tests. Molecular typing was determined
      by pulsed field gel electrophoresis (PFGE). MBL-encoding genes, as well as their
      genetic context, were identified by polymerase chain reaction (PCR) and
      sequencing. The location of blaIMP-16 was determined by plasmid electrophoresis,
      Southern blot and hybridization. Transcriptional levels of blaIMP-16, mexB, mexD,
      mexF, mexY, ampC and oprD were determined by semi-quantitative real time PCR. The
      P. aeruginosa isolates studied, Pa30 and Pa43, showed imipenem and meropenem
      susceptibility by automated testing. Agar dilution assays confirmed meropenem
      susceptibility whereas both isolates showed low level of imipenem resistance.
      Pa30 and Pa43 were phenotypically detected as MBL producers. PFGE revealed their
      clonal relatedness. blaIMP-16 was identified in both isolates, carried as a
      single cassette in a class 1 integron that was embedded in a plasmid of about 60
      Kb. Pa30 and Pa43 overexpressed MexAB-OprM, MexCD-OprJ and MexXY-OprM efflux
      systems and showed basal transcriptional levels of ampC and oprD. MBL-producing
      P. aeruginosa that are not resistant to meropenem may represent a risk for
      therapeutic failure and act as silent reservoirs of MBL-encoding genes.

PMID- 22990964
TI  - Proteolytic activity in the adult and larval stages of the human roundworm
      parasite Angiostrongylus costaricensis.
AB  - Angiostrongylus costaricensis is a nematode that causes abdominal
      angiostrongyliasis, a widespread human parasitism in Latin America. This study
      aimed to characterize the protease profiles of different developmental stages of
      this helminth. First-stage larvae (L1) were obtained from the faeces of infected
      Sigmodon hispidus rodents and third-stage larvae (L3) were collected from
      mollusks Biomphalaria glabrata previously infected with L1. Adult worms were
      recovered from rodent mesenteric arteries. Protein extraction was performed after
      repeated freeze-thaw cycles followed by maceration of the nematodes in 40 mM Tris
      base. Proteolysis of gelatin was observed by zymography and found only in the
      larval stages. In L3, the gelatinolytic activity was effectively inhibited by
      orthophenanthroline, indicating the involvement of metalloproteases. The
      mechanistic class of the gelatinases from L1 could not be precisely determined
      using traditional class-specific inhibitors. Adult worm extracts were able to
      hydrolyze haemoglobin in solution, although no activity was observed by
      zymography. This haemoglobinolytic activity was ascribed to aspartic proteases
      following its effective inhibition by pepstatin, which also inhibited the
      haemoglobinolytic activity of L1 and L3 extracts. The characterization of
      protease expression throughout the A. costaricensis life cycle may reveal key
      factors influencing the process of parasitic infection and thus foster our
      understanding of the disease pathogenesis.

PMID- 22990965
TI  - Hepatitis B virus genotypes in Southeast Brazil and its relationship with
      histological features.
AB  - Data concerning the relationship between hepatitis B virus (HBV) genotypes and
      liver histology are scarce. The aim of this study was to compare HBV non-B and
      non-C genotypes according to demographic features, clinical status, HBV-DNA
      levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive
      chronic HBV-infected patients were enrolled during two-year period and data were
      prospectively collected. Sera were tested for HBV genotyping using restriction
      fragment length polymorphism. Liver biopsy was obtained from patients with either
      increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the
      most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17
      (14%), B in one (1%) and C in two (2%). There was no association between HBV
      genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode
      of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p =
      0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F
      (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity
      index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A
      (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p =
      0.01). Genotype A was the most prevalent in chronic HBV-infected patients and
      genotype D patients presented with less intense liver disease.

PMID- 22990966
TI  - A study of multidrug-resistant tuberculosis in risk groups in the city of Santos,
      Sao Paulo, Brazil.
AB  - Monitoring the extent of and trends in multidrug-resistant tuberculosis (MDR-TB)
      is a priority of the Brazilian National Tuberculosis Control Programme. The
      current study aimed to estimate the incidence of MDR-TB, describe the profile of
      TB drug resistance in risk groups and examine whether screening for MDR-TB
      adhered to the recommended guidelines. A descriptive study that examined
      diagnosed cases of pulmonary TB was conducted in the city of Santos, Brazil,
      between 2000-2004. Of the 2,176 pulmonary TB cases studied, 671 (30.8%) met the
      criteria for drug sensitivity testing and, of these cases, 31.7% (213/671) were
      tested. Among the tested cases, 9.4% were resistant to one anti-TB drug and 15%
      were MDR. MDR was observed in 11.6% of 86 new TB cases and 17.3% of 127
      previously treated cases. The average annual incidence of MDR-TB was 1.9 per
      100,000 inhabitants-years. The extent of known MDR-TB in the city of Santos is
      high, though likely to be underestimated. Our study therefore indicates an
      inadequate adherence to the guidelines for MDR-TB screening and suggests the
      necessity of alternative strategies of MDR-TB surveillance.

PMID- 22990967
TI  - Lutzomyia longipalpis abundance in the city of Posadas, northeastern Argentina:
      variations at different spatial scales.
AB  - The distribution of Lutzomyia longipalpis is heterogeneous with a pattern of high
      abundance areas (HAAs) embedded in a matrix of low abundance areas (LAAs). The
      objective of this study was to describe the variability in the abundance of Lu.
      longipalpis at two different spatial levels and to analyse the relationship
      between the abundance and multiple environmental variables. Of the environmental
      variables analysed in each household, the condition that best explained the
      differences in vector abundance between HAA-LAA was the variable "land_grass",
      with greater average values in the peridomestic environments within the LAA, and
      the variables "#sp tree", "#pots" and "dist_water" that were higher in the HAA.
      Of the environmental variables analysed in the patches, the variable
      "unpaved_streets" was higher in the LAAs and the variable "prop_inf_dogs" was
      higher in the HAAs. An understanding of the main environmental variables that
      influence the vector distribution could contribute to the development of
      strategies for the prevention and control of visceral leishmaniasis (VL). This is
      the first work in which environmental variables are analysed at the micro-scale
      in urban areas at the southern edge of the current range of Lu. longipalpis. Our
      results represent a significant contribution to the understanding of the
      abundance of the vector in the peridomestic habitats of the region.

PMID- 22990968
TI  - Molecular characterisation of Bartonella species in cats from Sao Luis, state of
      Maranhao, north-eastern Brazil.
AB  - Bartonella species are fastidious bacteria that predominantly infect mammalian
      erythrocytes and endothelial cells and cause long-lasting bacteraemia in their
      reservoir hosts. Reports that describe the epidemiology of bartonellosis in
      Brazil are limited. This study aimed to detect and characterise Bartonella spp
      DNA from cat blood samples in Sao Luis, Maranhao, north-eastern Brazil. Among 200
      cats tested for multiple genes, nine (4.5%) were positive for Bartonella spp: six
      cats for Bartonella henselae and three for Bartonella clarridgeiae. Based on the
      phylogenetic analysis of four genes, the B. henselae strain matched strains
      previously observed in Brazil and was positioned in the same clade as B. henselae
      isolates from the United States of America. Moreover, sequence alignment
      demonstrated that the B. clarridgeiae strain detected in the present study was
      the same as the one recently detected in cats from southern Brazil.

PMID- 22990969
TI  - Detection of enteric viruses in recreational waters of an urban lagoon in the
      city of Rio de Janeiro, Brazil.
AB  - The aim of this study was to determine the occurrences of the group A rotavirus
      (RVA), norovirus (NoV) and human adenovirus (HAdV) in the surface waters of an
      urban lagoon (Rodrigo de Freitas Lagoon) in the city of Rio de Janeiro, Brazil.
      During one year of surveillance, water samples were obtained from the lagoon and
      other interconnected ecosystems (river and beach). The samples were concentrated
      using an adsorption-elution method with a negatively charged membrane and tested
      by qualitative and quantitative polymerase chain reaction assays. RVA was the
      most prevalent virus detected (24.3%) with a viral load ranging from 3.0 x 101
      5.6 x 10(4) genome copies/L, followed by NoV (18.8%) and HAdV (16.7%).
      Considering water samples suitable for bathing, according to Escherichia coli
      criterion (< 2,000 most probable number/100 mL), viruses were detected in 50%
      (57/114) of them. Physicochemical parameters were also measured and showed
      possible correlations between turbidity and RVA presence and between pH and NoV
      presence. These data demonstrate the importance of considering viral parameters
      to ensure water quality and the utilisation of these parameters as additional
      tools for the characterisation of environmental contamination.

PMID- 22990970
TI  - The zinc finger protein TcZFP2 binds target mRNAs enriched during Trypanosoma
      cruzi metacyclogenesis.
AB  - Trypanosomes are parasitic protozoa in which gene expression is primarily
      controlled through the regulation of mRNA stability and translation. This post
      transcriptional control is mediated by various families of RNA-binding proteins,
      including those with zinc finger CCCH motifs. CCCH zinc finger proteins have been
      shown to be essential to differentiation events in trypanosomatid parasites.
      Here, we functionally characterise TcZFP2 as a predicted post-transcriptional
      regulator of differentiation in Trypanosoma cruzi. This protein was detected in
      cell culture-derived amastigotes and trypomastigotes, but it was present in
      smaller amounts in metacyclic trypomastigote forms of T. cruzi. We use an
      optimised recombinant RNA immunopreciptation followed by microarray analysis
      assay to identify TcZFP2 target mRNAs. We further demonstrate that TcZFP2 binds
      an A-rich sequence in which the adenosine residue repeats are essential for high
      affinity recognition. An analysis of the expression profiles of the genes
      encoding the TcZFP2-associated mRNAs throughout the parasite life cycle by
      microarray hybridisation showed that most of the associated mRNAs were
      upregulated in the metacyclic trypomastigote forms, also suggesting a role for
      TcZFP2 in metacyclic trypomastigote differentiation. Knockdown of the orthologous
      Trypanosoma brucei protein levels showed ZFP2 to be a positive regulator of
      specific target mRNA abundance.

PMID- 22990971
TI  - Human bocavirus 1 and 3 infection in children with acute gastroenteritis in
      Brazil.
AB  - To determine the positivity rate of human bocavirus (HBoV) 1 and 3 among children
      who presented with acute gastroenteritis symptoms during the period of 1994-2004
      in the Central-West Region of Brazil, 762 faecal samples were tested using
      polymerase chain reaction (PCR) for the detection of HBoV DNA. Primers for a
      segment of the non-structural viral protein 1 (NS1) gene of HBoV-1 and HBoV-3
      were used. Twelve HBoV-positive samples were further characterised via genomic
      sequencing and phylogenetic analysis. Of the samples tested, 5.8% (n = 44) were
      positive for HBoV-1 or HBoV-3 and co-infection was observed in 14 (31.8%) of the
      44 HBoV-positive samples. Nine of the 14 samples were also positive for Rotavirus
      A and five were positive for Aichi virus. The genomic sequencing of the NS1
      partial sequence of 12 HBoV-samples showed that 11 samples were characterised as
      HBoV-1 and that one was characterised as HBoV-3. The phylogenetic analysis showed
      that the HBoV-1 samples had a high sequence homology to others previously
      identified in China, Sweden and Brazil. This is the first study conducted in the
      Central-West Region of Brazil to detect HBoV-1 and HBoV-3 in faecal samples from
      children with acute gastroenteritis. Further studies are required to define the
      role of HBoVs as aetiological agents of gastroenteritis.

PMID- 22990972
TI  - Molecular characterisation of dengue virus type 1 reveals lineage replacement
      during circulation in Brazilian territory.
AB  - Dengue fever is the most important arbovirus infection found in tropical regions
      around the world. Dispersal of the vector and an increase in migratory flow
      between countries have led to large epidemics and severe clinical outcomes, such
      as dengue haemorrhagic fever and dengue shock syndrome. This study analysed the
      genetic variability of the dengue virus serotype 1 (DENV-1) in Brazil with regard
      to the full-length structural genes C/prM/M/E among 34 strains isolated during
      epidemics that occurred in the country between 1994-2011. Virus phylogeny and
      time of divergence were also evaluated with only the E gene of the strains
      isolated from 1994-2008. An analysis of amino acid differences between these
      strains and the French Guiana strain (FGA/89) revealed the presence of important
      nonsynonymous substitutions in the amino acid sequences, including residues E297
      (Met->Thr) and E338 (Ser->Leu). A phylogenetic analysis of E proteins comparing
      the studied isolates and other strains selected from the GenBank database showed
      that the Brazilian DENV-1 strains since 1982 belonged to genotype V. This
      analysis also showed that different introductions of strains from the 1990s
      represented lineage replacement, with the identification of three lineages that
      cluster all isolates from the Americas. An analysis of the divergence time of
      DENV-1 indicated that the lineage circulating in Brazil emerged from an ancestral
      lineage that originated approximately 44.35 years ago.

PMID- 22990973
TI  - Coccidioidomycosis in armadillo hunters from the state of Ceara, Brazil.
AB  - Coccidioidomycosis is a systemic mycosis with a variable clinical presentation.
      Misdiagnosis of coccidioidomycosis as bacterial pneumopathy leads to
      inappropriate prescription of antibiotics and delayed diagnosis. This report
      describes an outbreak among armadillo hunters in northeastern Brazil in which an
      initial diagnosis of bacterial pneumonia was later confirmed as
      coccidioidomycosis caused by Coccidioides posadasii. Thus, this mycosis should be
      considered as an alternative diagnosis in patients reporting symptoms of
      pneumonia, even if these symptoms are only presented for a short period, who are
      from areas considered endemic for this disease.

PMID- 22990974
TI  - Distinct subcellular localization of tRNA-derived fragments in the infective
      metacyclic forms of Trypanosoma cruzi.
AB  - Small non-coding RNAs derived from transfer RNAs have been identified as a
      broadly conserved prokaryotic and eukaryotic response to stress. Their presence
      coincides with changes in developmental state associated with gene expression
      regulation. In the epimastigote form of Trypanosoma cruzi, tRNA fragments
      localize to posterior cytoplasmic granules. In the infective metacyclic form of
      the parasite, we found tRNA-derived fragments to be abundant and evenly
      distributed within the cytoplasm. The fragments were not associated with
      polysomes, suggesting that the tRNA-derived fragments may not be directly
      involved in translation control in metacyclics.

PMID- 22990975
TI  - The in vivo antimalarial activity of methylene blue combined with pyrimethamine,
      chloroquine and quinine.
AB  - The effectiveness of methylene blue (MB) combined with pyrimethamine (PYR),
      chloroquine (CQ) or quinine (Q) was examined in a classical four-day suppressive
      test against a causative agent of rodent malaria, Plasmodium berghei. A marked
      potentiation was observed when MB was administered at a non-curative dose of 15
      mg/kg/day in combination with PYR (0.19 mg/kg/day) or Q (25 mg/kg/day). No
      synergy was found between MB (15 mg/Kg) and CQ (0.75 mg/Kg). Our results suggest
      that the combination of MB with PYR or Q may improve the efficacy of these
      currently used antimalarial drugs.

PMID- 22990976
TI  - Upregulation of hsa-miR-125b in HTLV-1 asymptomatic carriers and HTLV-1
      associated myelopathy/tropical spastic paraparesis patients.
AB  - The retrovirus human T lymphotropic virus type 1 (HTLV-1) promotes spastic
      paraparesis, adult T cell leukaemia and other diseases. Recently, some human
      microRNAs (miRNAs) have been described as important factors in host-virus
      interactions. This study compared miRNA expression in control individuals,
      asymptomatic HTLV-1 carriers and HTLV-1 associated myelopathy (HAM)/tropical
      spastic paraparesis patients. The proviral load and Tax protein expression were
      measured in order to characterize the patients. hsa-miR-125b expression was
      significantly higher in patients than in controls (p = 0.0285) or in the HAM
      group (p = 0.0312). Therefore, our findings suggest that miR-125b expression can
      be used to elucidate the mechanisms of viral replication and pathogenic
      processes.

PMID- 22990977
TI  - Why do we need alternative tools to control mosquito-borne diseases in Latin
      America?
AB  - In this opinion paper, we discuss the potential and challenges of using the
      symbiont Wolbachia to block mosquito transmitted diseases such as dengue, malaria
      and chikungunya in Latin America.

PMID- 22990978
TI  - Improvement of the yields of recombinant actin and myosin V-HMM in the insect
      cell/baculovirus system by the addition of nutrients to the high-density cell
      culture.
AB  - Baculovirus infection of Sf9 cells at high densities, such as during mid- and
      late exponential phase, often results in a significant reduction of protein yield
      per cell, compared to the early exponential phase. Nutrient depletion has been
      considered as a major cause for the decreased protein yield. In this study, we
      report that the addition of nutrients (glucose, yeastolate ultrafiltrate, and
      lactalbumin hydrolysate) and small fraction of fresh medium at time of infection
      restores the expression level of actin and myosin V-HMM at late exponential phase
      (11.3 * 10(6) cells/ml) to that at early exponential phase (1.0 * 10(6)
      cells/ml). The relative yields of actin and myosin V-HMM were approximately equal
      at both phases (typically 200 mg of actin and 5 mg of myosin V-HMM per 10(10)
      cells), i.e., the volumetric yield of proteins from the cell culture at late
      exponential phase was approximately tenfold higher than at early exponential
      phase. The functionality of the recombinant actin and myosin V-HMM was confirmed
      by measuring the rate of actin polymerization, actin-activated ATPase, and the
      gliding velocity of actin filaments in an in vitro motility assay.

PMID- 22990979
TI  - Whole-genome microRNA expression profiling identifies a 5-microRNA signature as a
      prognostic biomarker in Chinese patients with primary glioblastoma multiforme.
AB  - BACKGROUND: More reliable clinical outcome prediction is required to better guide
      more personalized treatment for patients with primary glioblastoma multiforme
      (GBM). The objective of this study was to identify a microRNA expression
      signature to improve outcome prediction for patients with primary GBM. METHODS: A
      cohort of Chinese patients with primary GBM (n = 82) was analyzed using whole
      genome microRNA expression profiling with patients divided into a training set
      and a testing set. Cox regression and risk-score analyses were used to develop a
      5-microRNA signature using 41 training samples. The signature was validated in 41
      other test samples, in an independent cohort of 35 patients with GBM, and in the
      Cancer Genome Atlas data set. RESULTS: Patients who had high risk scores
      according to the 5-microRNA signature had poor overall survival and progression
      free survival compared with patients who had low risk scores. Multivariate Cox
      analysis indicated that the 5-microRNA signature was an independent prognostic
      biomarker after adjusting for other clinicopathologic and genetic factors, such
      as extent of resection, temozolomide chemotherapy, preoperative Karnofsky
      performance status score, isocitrate dehydrogenase 1 (IDH1) mutation, and O-6
      methylguanine-DNA methyltransferase (MGMT) promoter methylation status.
      CONCLUSIONS: The 5-microRNA signature was identified as an independent risk
      predictor that identified patients who had a high risk of unfavorable outcome,
      demonstrating its potential for personalizing cancer management. The authors
      concluded that this signature should be evaluated in further prospective studies.

PMID- 22990981
TI  - Toxin binding reveals two open state structures for one acid-sensing ion channel.
AB  - Of the three principal conformations of acid-sensing ion channels (ASICs)-
      closed, open and desensitized--only the atomic structure of the desensitized
      conformation had been known. Two recent papers report the crystal structure of
      chicken ASIC1 in complex with the spider toxin psalmotoxin 1, and one of these
      studies finds that, depending on the pH, channels are in two different open
      conformations. Compared with the desensitized conformation, toxin binding induces
      only subtle structural changes in the lower part of the large extracellular
      domain but a complete rearrangement of the two transmembrane domains (TMDs),
      suggesting that desensitization gating (the transition from open to desensitized)
      is mainly associated with conformational rearrangements of the TMDs. Moreover,
      the study reveals how two different arrangements of the TMDs in the open state
      give rise to ion pores with different selectivity for monovalent cations.

PMID- 22990982
TI  - Lifetime of combustion-generated environmentally persistent free radicals on
      Zn(II)O and other transition metal oxides.
AB  - Previous studies indicated that Environmentally Persistent Free Radicals (EPFRs)
      are formed in the post-flame, cool zone of combustion. They result from the
      chemisorption of gas-phase products of incomplete combustion (particularly
      hydroxyl- and chlorine-substituted aromatics) on Cu(II)O, Fe(III)(2)O(3), and
      Ni(II)O domains of particulate matter (fly ash or soot particles). This study
      reports our detailed laboratory investigation on the lifetime of EPFRs on
      Zn(II)O/silica surface. Similarly, as in the case of other transition metals,
      chemisorption of the adsorbate on the Zn(II)O surface and subsequent transfer of
      electron from the adsorbate to the metal forms a surface-bound EPFR and a reduced
      metal ion center. The EPFRs are stabilized by their interaction with the metal
      oxide domain surface. The half-lives of EPFRs formed on Zn(II)O domains were the
      longest observed among the transition metal oxides studied and ranged from 3 to
      73 days. These half-lives were an order of magnitude longer than those formed on
      nickel and iron oxides, and were 2 orders of magnitude longer compared to the
      EPFRs on copper oxide which have half-lives only on the order of hours. The
      longest-lived radicals on Zn(II)O correspond to the persistency in ambient air
      particles of almost a year. The half-life of EPFRs was found to correlate with
      the standard reduction potential of the associated metal.

PMID- 22990983
TI  - Multifocal metachronous giant cell tumour in bilateral upper limb: a rare case
      presentation.
AB  - Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour and
      accounts for 20 % of all benign bone tumours and 5 % of all bone tumours.
      Multicentric GCT of bone is a rare entity and has increased prevalence of
      involvement of the small bones of hands and feet in multicentric GCT. The
      clinical behaviour in multicentric GCTs tends to be aggressive as in recurrent
      GCTs. En-bloc resection remains the most successful surgical technique for
      treating both multicentric and solitary lesions. We report a 14-year-old female
      patient presenting with metachronous benign GCT located at the right proximal
      humerus and subsequent lesions in left hand and left proximal humerus. The case
      was treated with multimodality therapy including en-bloc resection along with
      bisphosphonate therapy over a period of 5 years.

PMID- 22990984
TI  - Is it ever safe to discharge a chondrosarcoma of pelvis? Report of a local
      recurrence after 10 years.
AB  - Late local recurrence is rare in conventional pelvic chondrosarcoma. Adequacy of
      surgical margins is an important factor of disease control and majority of local
      recurrences occur within 5 years of surgery. We present a case of a 43-year-old
      female who underwent a PII/III resection of a Grade 1 to 2 chondrosarcoma and was
      discharged from routine follow-up after a 10-year disease-free interval. Thirteen
      years after the initial excision, she re-presented with a large local recurrence
      requiring a hindquarter amputation. Local recurrence more than 10 years after the
      index operation is uncommon in pelvic chondrosarcoma. The cases mentioned in
      previous studies lack documentation making recommendations on the subject
      difficult. Routine post-operative cross-sectional imaging is essential in pelvic
      chondrosarcoma even when tumour-free margins are achieved as there is no adequate
      adjuvant therapy to deal with microscopic disease.

PMID- 22990985
TI  - Aminoglycoside antibiotics bind to the influenza A virus RNA promoter.
AB  - Aminoglycosides bind to the influenza A virus promoter (vRNA) at submicromolar
      concentration. The complex structure between the vRNA and neomycin illustrates
      that binding of neomycin causes a conformational change which would affect
      further transcription processes. Thus, aminoglycosides represent lead compounds
      for the discovery of antiviral therapeutics against influenza A virus.

PMID- 22990987
TI  - Percutaneous laser ablation under ultrasound guidance for fetal hyperechogenic
      microcystic lung lesions with hydrops: a single center cohort and a literature
      review.
AB  - OBJECTIVE: To evaluate the perinatal outcomes in hydropic fetuses with congenital
      microcystic pulmonary lesions that underwent percutaneous, invasive, laser
      therapy. METHOD: This retrospective study reviews the literature and our
      experience between 2004 and 2010. Characteristics of the cystic lung lesions,
      liquor volume (presence of polyhydramnios or not), localization of ablation
      (vascular vs interstitial) and gestational age at which the procedure was
      performed were related to outcome (survival). RESULTS: In total, 16 fetuses with
      congenital lung lesions underwent 'invasive' percutaneous laser ablation, seven
      performed in our center and nine published cases. Survival rate was higher in
      fetuses with a subsequent postnatal diagnosis of bronchopulmonary sequestration
      (87.5%) compared with congenital adenomatoid malformation (28.6%; p = 0.04). The
      technique of vascular ablation was more successful (100%) than interstitial
      ablation (25.0%, p < 0.01). CONCLUSION: Percutaneous vascular laser ablation
      seems to be effective for bronchopulmonary sequestration in hydropic fetuses.
      Outcomes were worst following interstitial ablation for microcystic congenital
      adenomatoid with hydrops.

PMID- 22990988
TI  - The influence of a vestibular dysfunction on the motor development of hearing
      impaired children.
AB  - OBJECTIVES/HYPOTHESIS: To identify the predictive ability of vestibular function
      test results on motor performance among hearing-impaired children. STUDY DESIGN:
      Cross-sectional study. METHODS: Fifty-one typically developing children and 48
      children with a unilateral (n = 9) or bilateral hearing impairment (n = 39) of
      more than 40 dB HL between 3 and 12 years were tested by the Movement Assessment
      Battery for Children-Second Edition (M ABC-2), clinical balance tests,
      posturography, rotatory chair testing, and vestibular evoked myogenic potential
      (VEMP). From the group of hearing-impaired children, 23 had cochlear implants.
      RESULTS: Balance performance on M ABC-2, clinical balance tests, as well as the
      sway velocity assessed by posturography in bipedal stance on a cushion with eyes
      closed and in unilateral stance differed significantly between both groups.
      Presence of a VEMP response is an important clinical parameter because comparison
      of the motor performance among hearing-impaired children between those with
      present and absent VEMPs showed significant differences in balance performance.
      The three most important predictor variables on motor performance by bivariate
      regression analyses are the vestibular-ocular reflex (VOR) gain value of the
      rotatory chair test at 0.01 and 0.05 Hz frequency, as well as the VEMP asymmetry
      ratio. Multivariate regression analyses suggest that the VOR asymmetry value of
      the rotatory chair test at 0.05 Hz and the etiology of the hearing loss seem to
      have additional predictive value. CONCLUSIONS: Hearing-impaired children are at
      risk for balance deficits. A combination of rotatory chair testing and VEMP
      testing can predict the balance performance.

PMID- 22990986
TI  - Wearable and implantable pancreas substitutes.
AB  - A lifelong-implanted and completely automated artificial or bioartificial
      pancreas (BAP) is the holy grail for type 1 diabetes treatment, and could be a
      definitive solution even for other severe pathologies, such as pancreatitis and
      pancreas cancer. Technology has made several important steps forward in the last
      years, providing new hope for the realization of such devices, whose feasibility
      is strictly connected to advances in glucose sensor technology, subcutaneous and
      intraperitoneal insulin pump development, the design of closed-loop control
      algorithms for mechatronic pancreases, as well as cell and tissue engineering and
      cell encapsulation for biohybrid pancreases. Furthermore, smart integration of
      the mentioned components and biocompatibility issues must be addressed, bearing
      in mind that, for mechatronic pancreases, it is most important to consider how to
      recharge implanted batteries and refill implanted insulin reservoirs without
      requiring periodic surgical interventions. This review describes recent
      advancements in technologies and concepts related to artificial and bioartificial
      pancreases, and assesses how far we are from a lifelong-implanted and self
      working pancreas substitute that can fully restore the quality of life of a
      diabetic (or other type of) patient.

PMID- 22990989
TI  - Altered homeostasis of systemic glucocorticoids as related to obesity, glucose
      tolerance, and smoking.
AB  - The hypothalamic-pituitary-adrenal axis is supposed to be involved in the
      pathogenesis of the metabolic disorders. Differences in adipose tissues and
      parameters of insulin resistance are linked to steroid homeostasis. We assessed
      the correlation of fat tissue distribution, gender, and glucose control with
      levels of systemic corticosteroid-binding globulin (CBG), free cortisol (FuF),
      and total cortisol (FuM). Data of 1 114 patients with overweight, lipid
      disorders, and impaired glucose tolerance were collected. Blood samples were
      sorted according to gender and anthropometric measures. Variable-association was
      calculated using the Spearman Rank Correlation coefficient and tested for
      significance (p<0.05 and p<0.01). CBG and FuF were consistently negatively
      correlated to each weight parameter. Especially in women, fat mass index (FMI)
      was significantly negatively correlated with CBG-levels. While CBG levels dropped
      with increasing age, FuF showed an inverse behavior. Glycohemoglobin levels
      showed negative correlations with CBG while fasting glucose did not. Both changes
      were associated with significant increases in FuF. All negative correlations to
      cortisol and its binding globulin with regards to weigh- and glucose-control
      parameters were absent in smokers compared to nonsmokers. Our observations
      suggest that different weight parameters correspond to adrenal steroids and their
      buffer systems. Especially in women, CBG levels might serve as prognostic marker
      for the fat mass. In addition, CBG levels may predict long term blood glucose
      control more reliably than FG. However, the value of CBG as an indirect surrogate
      marker for obesity and glucose is limited in smokers.

PMID- 22990990
TI  - Proinsulin C-peptide inhibits lipolysis in diabetic rat adipose tissue through
      phosphodiestrase-3B enzyme.
AB  - We have previously reported that C-peptide modulates insulin-mediated inhibition
      of lipolysis and glucose consumption but has no significant effects per se on
      adipose tissue of normal rats. It has been repeatedly observed that certain
      actions of C-peptide are restricted to the diabetic states. In the present study,
      therefore, we examined whether C-peptide alters lipolysis in adipose tissue of
      diabetic rats. Rats were rendered diabetic by streptozotocin and divided into 2
      groups; insulin treated and untreated. Retroperitoneal adipose tissue was excised
      aseptically, subjected to organ culture and incubated with rat C-peptide,
      insulin, or a combination of both peptides in the presence or absence of
      isoproterenol. Tissue lipolysis was assessed by the rate of glycerol release into
      the culture media. The cultures were pretreated with cilostamide, a
      phosphodiesterase-3B enzyme inhibitor, when the role of this enzyme was to be
      examined. C-Peptide on its own, like insulin, significantly inhibited
      isoproterenol-stimulated lipolysis in the adipose tissue of untreated diabetic
      rats. The effect was enhanced by a combination of C-peptide and insulin. Notably,
      the C-peptide's effect was totally blocked in the presence of cilostamide. In the
      adipose tissue of insulin treated rats, however, C-peptide failed to show any
      significant antilipolytic effects. These data show that C-peptide has the
      potential to act, conditionally, as an antilipolytic hormone by activating
      phosphodiesterase-3B and suggest that the action may contribute to the C
      peptide's beneficial effects on diabetes-induced complications.

PMID- 22990991
TI  - Vitamin D levels and insulin resistance in children born with severe growth
      restriction.
AB  - This study was designed to examine differences in serum 25(OH)D levels between
      small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA)
      prepubertal children in correlation with birth weight and indices of insulin
      resistance and beta-cell function. Sixty-five nonobese children were examined at
      age 5-7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and
      waist circumference were recorded and fasting serum levels of glucose, insulin,
      25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model
      assessment for insulin resistance (HOMA-IR) and the beta-cell function index
      (HOMA-beta%) were estimated. The mean level of 25(OH)D was higher in the SGA
      group (26.2+/-10 vs. 17.2+/-7 ng/ml, p<0.01) but that of PTH was no different.
      The insulin resistance and beta-cell function indices were higher in the SGA
      group: HOMA-IR 1.34+/-0.67 vs. 0.99+/-0.53, and HOMA-beta% 135+/-56 vs. 97+/-60
      in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated
      with HOMA-beta% but not with HOMA-IR or insulin. In multiple regression, in the
      total cohort 25(OH)D and HOMA-IR were independently negatively correlated with
      birth weight (beta= - 0.31, beta= - 0.36, p<0.05) respectively. In conclusion, at
      prepuberty severely in utero growth restricted children have increased birth
      weight dependent levels of 25(OH)D, which might exert a regulatory role on beta
      cell function.

PMID- 22990993
TI  - Poor science does not explain why papers are rejected.

PMID- 22990992
TI  - Expression profiles of the nuclear receptors and their transcriptional
      coregulators during differentiation of neural stem cells.
AB  - Neural stem cells (NSCs) are pluripotent precursors with the ability to
      proliferate and differentiate into 3 neural cell lineages, neurons, astrocytes
      and oligodendrocytes. Elucidation of the mechanisms underlying these biologic
      processes is essential for understanding both physiologic and pathologic neural
      development and regeneration after injury. Nuclear hormone receptors (NRs) and
      their transcriptional coregulators also play crucial roles in neural development,
      functions and fate. To identify key NRs and their transcriptional regulators in
      NSC differentiation, we examined mRNA expression of 49 NRs and many of their
      coregulators during differentiation (0-5 days) of mouse embryonic NSCs induced by
      withdrawal of fibroblast growth factor-2 (FGF2). 37 out of 49 NRs were expressed
      in NSCs before induction of differentiation, while receptors known to play major
      roles in neural development, such as THRalpha, RXRs, RORs, TRs, and COUP-TFs,
      were highly expressed. CAR, which plays important roles in xenobiotic metabolism,
      was also highly expressed. FGF2 withdrawal induced mRNA expression of RORgamma,
      RXRgamma, and MR by over 20-fold. Most of the transcriptional coregulators
      examined were expressed basally and throughout differentiation without major
      changes, while FGF2 withdrawal strongly induced mRNA expression of several
      histone deacetylases (HDACs), including HDAC11. Dexamethasone and aldosterone,
      respectively a synthetic glucocorticoid and natural mineralocorticoid, increased
      NSC numbers and induced differentiation into neurons and astrocytes. These
      results indicate that the NRs and their coregulators are present and/or change
      their expression during NSC differentiation, suggesting that they may influence
      development of the central nervous system in the absence or presence of their
      ligands.

PMID- 22990995
TI  - Preimplantation genetic testing.

PMID- 22990994
TI  - Prediction models for risk of developing type 2 diabetes: systematic literature
      search and independent external validation study.
AB  - OBJECTIVE: To identify existing prediction models for the risk of development of
      type 2 diabetes and to externally validate them in a large independent cohort.
      DATA SOURCES: Systematic search of English, German, and Dutch literature in
      PubMed until February 2011 to identify prediction models for diabetes. DESIGN:
      Performance of the models was assessed in terms of discrimination (C statistic)
      and calibration (calibration plots and Hosmer-Lemeshow test).The validation study
      was a prospective cohort study, with a case cohort study in a random subcohort.
      SETTING: Models were applied to the Dutch cohort of the European Prospective
      Investigation into Cancer and Nutrition cohort study (EPIC-NL). PARTICIPANTS:
      38,379 people aged 20-70 with no diabetes at baseline, 2506 of whom made up the
      random subcohort. OUTCOME MEASURE: Incident type 2 diabetes. RESULTS: The review
      identified 16 studies containing 25 prediction models. We considered 12 models as
      basic because they were based on variables that can be assessed non-invasively
      and 13 models as extended because they additionally included conventional
      biomarkers such as glucose concentration. During a median follow-up of 10.2 years
      there were 924 cases in the full EPIC-NL cohort and 79 in the random subcohort.
      The C statistic for the basic models ranged from 0.74 (95% confidence interval
      0.73 to 0.75) to 0.84 (0.82 to 0.85) for risk at 7.5 years. For prediction models
      including biomarkers the C statistic ranged from 0.81 (0.80 to 0.83) to 0.93
      (0.92 to 0.94). Most prediction models overestimated the observed risk of
      diabetes, particularly at higher observed risks. After adjustment for differences
      in incidence of diabetes, calibration improved considerably. CONCLUSIONS: Most
      basic prediction models can identify people at high risk of developing diabetes
      in a time frame of five to 10 years. Models including biomarkers classified cases
      slightly better than basic ones. Most models overestimated the actual risk of
      diabetes. Existing prediction models therefore perform well to identify those at
      high risk, but cannot sufficiently quantify actual risk of future diabetes.

PMID- 22990996
TI  - Industry-university research contracts are damaging.

PMID- 22990997
TI  - New psychosocial interventions are needed in early dementia.

PMID- 22990998
TI  - The "curse of the registrar".

PMID- 22990999
TI  - We must reclaim public health from private corporate interests.

PMID- 22991000
TI  - The most important public health debate of modern times.

PMID- 22991001
TI  - 20 mph speed limits are the right policy for sociability, safety, and a healthy
      population.

PMID- 22991002
TI  - All systems can be hacked.

PMID- 22991003
TI  - Time to think about a universal system, again?

PMID- 22991004
TI  - Extra safeguards are needed.

PMID- 22991005
TI  - Safety of vulnerable children could be put at risk.

PMID- 22991006
TI  - Why have prison needle exchange programmes not yet been rolled out in the UK?

PMID- 22991007
TI  - Clinical decision units can provide necessary care of renal colic.

PMID- 22991008
TI  - Final hearings begin in epic legal battle over Novartis drug in India.

PMID- 22991009
TI  - Improvements in US healthcare could save 75 000 lives a year, report says.

PMID- 22991010
TI  - European legislators tighten rules on drug safety.

PMID- 22991011
TI  - Colleges call for screening of all hospital patients to cut toll from venous
      thromboembolism.

PMID- 22991012
TI  - Rates and success rates of trial of labor after cesarean delivery in the United
      States, 1990-2009.
AB  - This study compares rates of trial of labor after Cesarean delivery (TOLAC) and
      rates of successful TOLAC between 1990 and 2009. Serial cross-sectional analyses
      were performed using the National Hospital Discharge Survey data to compare rates
      of TOLAC and TOLAC success between 1990 and 2009. Joinpoint regression was used
      to assess trends over time, and logistic regression with marginal effects was
      used to examine the unadjusted and adjusted significance and magnitude of trends.
      The rate of TOLAC reached a high of 51.8 % (95 % CI 47.8-55.8 %) in 1995 and a
      low of 15.9 % (95 % CI 13.8-18.0 %) in 2006, declined, on average, 4.2 (95 % CI 
      4.8 to -3.9) percentage points per year between 1996 and 2005. Rates increased
      significantly from 1990 to 1996 and 2005 to 2009. TOLAC success was at its
      highest rate in 2000, 69.8 % (95 % CI 65.2-74.3 %) and its lowest in 2008, 38.5 %
      (95 % CI 28.1-48.8 %). The rate of TOLAC success increased significantly between
      1990 and 2000, but declined thereafter an average of 3.4 % points per year (95 %
      CI -4.3 to -2.5). The rate of TOLAC in the US decreased between 1996 and 2005 and
      the rate of successful TOLAC has declined from 2000 to 2009. 

PMID- 22991013
TI  - The balANZ study--strengthening the evidence for neutral-pH solutions low in
      glucose degradation products.

PMID- 22991014
TI  - Balance about balANZ.

PMID- 22991016
TI  - Necrotizing fasciitis involving the peritoneal catheter exit site.

PMID- 22991015
TI  - The effects of biocompatible compared with standard peritoneal dialysis solutions
      on peritonitis microbiology, treatment, and outcomes: the balANZ trial.
AB  - BACKGROUND: A multicenter, multi-country randomized controlled trial (the balANZ
      study) recently reported that peritonitis rates significantly improved with the
      use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation
      products ("biocompatible") compared with standard solutions. The present paper
      reports a secondary outcome analysis of the balANZ trial with respect to
      peritonitis microbiology, treatment, and outcomes. METHODS: Adult incident PD
      patients with residual renal function were randomized to receive either
      biocompatible or conventional (control) PD solutions for 2 years. RESULTS: The
      safety population analysis for peritonitis included 91 patients in each group.
      The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95%
      confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the
      biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for
      the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p =
      0.01]. When specific causative organisms were examined, the rates of culture
      negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes
      were not significantly different between the biocompatible and control groups,
      although the biocompatible group did experience a significantly lower rate of non
      pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p =
      0.03). Initial empiric antibiotic regimens were comparable between the groups.
      Biocompatible fluid use did not significantly reduce the risk of peritonitis
      associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but
      did result in a shorter median duration of peritonitis-associated hospitalization
      (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated
      as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis
      associated technique failures and peritonitis-related deaths were comparable in
      the two groups. CONCLUSIONS: Biocompatible PD fluid use was associated with a
      broad reduction in gram-positive, gram-negative, and culture-negative peritonitis
      that reached statistical significance for non-pseudomonal gram-negative
      organisms. Peritonitis hospitalization duration was shorter, and peritonitis
      severity was more commonly rated as mild in patients receiving biocompatible PD
      fluids, although other peritonitis outcomes were comparable between the groups.

PMID- 22991017
TI  - Hemorrhage because of amyloid-related factor X deficiency after insertion of
      Tenckhoff catheter.

PMID- 22991018
TI  - Recurrent acute pancreatitis in a patient on peritoneal dialysis using 7.5%
      icodextrin.

PMID- 22991019
TI  - Prostate cancer metastatic to the peritoneum in a peritoneal dialysis patient.

PMID- 22991020
TI  - Successful long-term peritoneal dialysis in combination with once-weekly
      hemodialysis: a case report.

PMID- 22991021
TI  - Staphylococcus aureus peritonitis in two peritoneal dialysis patients: an
      uncommon complication of peripheral intravenous catheter infection.

PMID- 22991023
TI  - Peritoneal dialysis-related peritonitis with Klebsiella pneumoperitoneum
      mimicking viscus perforation.

PMID- 22991022
TI  - Is there a correlation between immunologic and psychological parameters in
      peritoneal dialysis patients?

PMID- 22991024
TI  - Peritonitis attributable to Kocuria rosea in a pediatric peritoneal dialysis
      patient.

PMID- 22991025
TI  - [Euthanasia in Belgium: a model for Spain?].

PMID- 22991026
TI  - [Euthanasia in Belgium].
AB  - The experience of the Netherlands in relation with the legalization and practice
      of euthanasia is better known in Spain than the Belgian experience in this
      matter. But the historical process of social debate in Belgium has many specific
      details which should be known by Spanish healthcare professionals, bioethicists,
      politicians and lawyers. This paper begins with a comparative analysis of both
      countries: Spain and Belgium and follows with a description of the milestones of
      the historical process of debating and, finally, passing the Belgian Law on
      Euthanasia in 2002. The next chapter consists of a description of the main
      contents of this important Law. The paper continues then with an approach to the
      epidemiology of the practice of euthanasia in Belgium and finishes with a
      description of the different positions of the actors of the process. Two
      positions are described more in depth: the opinion of the specialists in
      palliative care, and the opinion of the Catholic Church. The paper ends
      underlining the reason for the incorporation of the Belgian experience on
      euthanasia to the debate about the possibility of legalizing euthanasia in Spain.

PMID- 22991027
TI  - [Analysis of the European Directive 98/83/EC: paradigm of the justification and
      establishment of parametric values. The specific case of pesticides].
AB  - The health protection while ensuring the access to safe drinking water to the
      entire population is one of the main objectives all over the world. In this
      regard, the European Union, through Directive 98/83/EC, sets the parameters and
      maximum allowable parametric values to ensure the quality of water intended for
      human consumption. The aim of this paper is to give an overview of the values
      established in the European Directive in comparison with other countries and
      organizations, such as the World Health Organization, based on toxicological
      justification, doing special mention to the case of pesticides, in which there is
      great difference between the parametric values set. It also presents a comparison
      with the values fixed by the Directive 91/414/EEC concerning maximum residue
      limits of pesticides in food, highlighting the importance of joining criteria.

PMID- 22991028
TI  - [Late diagnosis of human immuno deficiency virus infection in the Madrid region
      (2007-2011)].
AB  - BACKGROUND: Early HIV infection diagnosis means tremendous benefits both for the
      individual, in particular, and public health, in general. The aim is to analyze
      the prevalence of delayed HIV-infection diagnosis in Madrid region and its
      related factors. METHODS: Descriptive study of HIV-diagnosed patients from
      January 2007 to September 2011. A study was conducted on all new cases where the
      CD4+ count was below 200/ul ('presentation with advanced HIV disease', PAD),
      350/ul ('late diagnosis', LD) and 500/ul. Descriptive and multivariate analysis
      by means of logistical regression. RESULTS: 3,347 HIV-diagnoses were reported,
      with CD4 count data available in 2,896 cases. 29.7% of which were PAD, 48.1% were
      LD and 67.7%<500 CD4+. Both in Spaniards and foreigners, age and mode of
      transmission intravenous drug users (IDU) and heterosexual (HTX), were
      independent variables regarding late presentation. In foreigners, geographical
      origin was likewise an independent variable. In Spaniards the probability of
      contracting PAD and LD rise with age and was higher in HTX (OR:3.38 [95%CI:2.29
      4.98) and 2.44 (1.67-3.56)] and IDU [OR: 2.41 (1.47-3.94) and 1.89 (1.19-3.01)]
      than men who have sex with men (MSM). For their part, probability of PAD and LD
      in foreigners increased with age and was higher in HTX (OR: 2.04 [1.44-2.89) and
      2.29 (1.61-3.25)] than MSM and Latin American nationals (OR: 2.56 [1.48-4.42) and
      2.29 (1.49-3.51)] and Sub-Saharan Africans (OR: 2.83 [1.52-5.28) and 2.52 (1.48
      4.30)] than Western Europeans. CONCLUSIONS: In the Madrid Region a high number of
      new diagnoses are carried out in patients who should have already been under
      treatment. What is more some of them also present a significant degree of immuno
      depression. Age, mode of transmission and geographical origin are closely related
      to late presentation.

PMID- 22991029
TI  - [Epidemiology of childhood tuberculosis in Spain: 2005-2009].
AB  - BACKGROUND: European recent data about paediatric tuberculosis point out the
      importance of evaluate the trends of the disease to study the recent
      transmission, as well as the necessity of improving the microbiological diagnosis
      in paediatric cases. The aim of this paper is to study the epidemiology and trend
      evolution of paediatric tuberculosis in Spain during the period 2005-2009 and to
      establish the epidemiological differences between adult and paediatric
      tuberculosis. METHODS: Data reported to the National Surveillance Net (Red
      Nacional de Vigilancia Epidemiologica) in Spain was checked. Lineal regression
      was developed to establish the trend of the disease in all, adult and paediatric
      cases. Bivariate and multivariate logistic regression was used to compare
      paediatric and adult cases reported in 2009 and estimate the influence of
      different factors in the development of the disease. RESULTS: A total 39775, 2690
      paediatrics (6.76%) cases of tuberculosis were reported during 2005-2009 period.
      Paediatric tuberculosis rates showed a slight increasing tendency (y=0.15x+7.8),
      while adult rates decrease during the period (y=-0.28x+20.2). In 2009, rates were
      8.1 and 18.3 cases/100,000 inhab. for children and adults respectively.
      Paediatric cases presented higher proportion of pulmonary locations (84% vs. 76%
      in adults) and lower percentages of cases confirmed by culture (51% vs. 82% in
      adults) and of cases in non-Spanish population (25% vs. 34%). CONCLUSIONS:
      Paediatric tuberculosis rates showed a slight increasing tendency, while global
      and adult rates decrease slightly during the period. Tuberculosis disease shows
      different epidemiology in children and adults, what it is important to take into
      account to design public heh interventions.

PMID- 22991030
TI  - [Incidence and variability of temporary disability due to anxiety disorders
      during 2009 in the Valencia Community, Spain].
AB  - BACKGROUND: Anxiety, dissociative and somatoform disorders (WHO-e 300) are the
      second cause of Temporary Disability (TD) in Spain. This is the main reason that
      justifies the analysis of the variability among primary health care centers (PHC)
      of the Valencian Community in the prescription processes of Temporary Disability
      for these disorders. METHODS: Epidemiological cross-sectional descriptive study
      of variability of TD processes initiated in 2009 corresponding to diagnosis e 300
      in 739 PHC from 23 health districts in the Valencian Community, where 25,859 TD
      processes for the diagnosis e 300 were prescribed. Traditional indicators of
      variation developed for the analysis of small areas were used to determine
      variability in the incidence rate of TD processes. The analysis of variance was
      used to determine the percentage of explanation of the factors studied. RESULTS:
      The average incidence rate obtained was of 1.08 for 100 individuals. The
      variation range was between 0.01 and 1.97 for percentiles P(5) to P(95). In the
      variance components analysis, the factor of health district explains the highest
      percentage of variability (22.12), followed by the factor province (20.21%),
      coastal areas (4.65%), teaching accreditation (2.44%) and the size of population
      assigned to each PHC (2.40%). CONCLUSIONS: Significant differences were observed
      in the incidence rate of TD processes for the diagnosis e 300. The PHCs with
      greater population pressure and those that are accredited had the highest rates
      of incidence.

PMID- 22991031
TI  - [Design and validation of a questionnaire exploring risky-driving patterns in
      young drivers].
AB  - BACKGROUND: Traffic Injuries are a major public health problem, especially among
      young people. However, we have not found any useful questionnaire designed in our
      country for the epidemiological research in this field. The objective of this
      study was to design and validate an easy and quickly-to-fill questionnaire aimed
      to collect information on how frequently university car drivers report to be
      involved in driving circumstances theoretically related to traffic crashes.
      METHODS: Between 2007 and 2010, a total of 1597 young undergraduate students at
      the University of Granada answered a self-administered questionnaire collecting
      information about exposure, accidents and involvement in 28 different driving
      circumstances. For designing this questionnaire, an extensive literature review
      was carried out and the opinions of five experts in a panel were also taken into
      account. By applying the tetracoric correlation coefficient, we conducted a
      factor analysis. Internal consistency was assessed using Cronbach's alpha
      coefficient. Finally, we evaluated the crude and adjusted association of each
      identified factor with the odds for having suffered an accident. RESULTS: After
      excluding 8 circumstances, the remaining ones were grouped into three factors:
      the first one included ten high-prevalence circumstances and explained 31.9% of
      the total variability. Meanwhile, the other two factors included five
      circumstances each one which respectively explained 15.2% and 12.5% of the
      variability. Cronbach's alpha coefficients ranged between 0.816 and 0.553. When
      adjustments according age, sex, years in possession of the driving license and
      intensity of exposure were made, the first factor obtained the score more
      strongly associated with the accident rate (OR = 1.51; CI95%: 1.25-1.85).
      CONCLUSIONS: The final version (20 circumstances) identified three factors
      related to higher accident rates among the young drivers. The first one
      integrated, among other circumstances, the excessive speed and driving while
      sleepy or tired and it was the most closely associated with the accident rate in
      the adjusted analysis. The second factor included, among others, the commission
      of driving offences, and the third one included driving under the influence of
      alcohol, not always wearing the seat belt and distractions.

PMID- 22991032
TI  - [Workers in primary health care and partner violence against women].
AB  - BACKGROUND: Morbidity associated to partner violence against women (PVAW) justify
      these patients repeated visits to Health Services. Primary Care is the ideal
      place for detection and first aid, due to its easy accesibility and continuated
      assistance. Nevertheless, numbers show important difficulties to achieve this
      goal. Our aim is to find out the level of knowledge, opinions, awareness about
      organizacional barriers and improvement proposals suggested by the workers of
      primary care. METHOD: Cross-sectional descriptive study using an anonymous and
      voluntary survey during the months of August and September 2010, targeted to all
      professionals who perform their work in a Primary Care Area of Madrid. We made a
      descriptive analysis of variables and used chi(2) to compare the answers.
      RESULTS: Answer rate is 170 (21.4%). There are stereotypes regarding battered
      woman and perpetrador. 118 (70.7%) professionals believe that this is a major
      problem and 154 (91.7%) that usually goes unnoticed. 91 (55.2%) know their legal
      commitments. 73 (51.8%) think that there are organizational barriers, among them:
      the burden of care 50(29%), lack of specific training 40(23.5), lack of knowledge
      about the procedure to be followed 20(11.8%) and about the professional
      responsabilities 12 (7%). CONCLUSIONS: All profesional categories showed an
      average level of knowledge, except for social workers that was high. Primary Care
      workers think that PVAW is an important issue that usually goes unnoticed. Half
      of them know the legal commitments o deteccion. There are organizacional barriers
      and stereotypes.

PMID- 22991033
TI  - [Heavy episodic drinking among adolescents: the association with negative mood
      states and family factors].
AB  - BACKGROUND: Heavy episodic drinking is widespread among adolescents, with serious
      health risks, including abuse / dependence in adulthood. The aim of this paper is
      to analyze the influence of negative mood states and some family variables on
      this type of drinking behavior among Catalan adolescents. METHODS: Cross
      sectional study of a representative sample of adolescents (age 14-18 years) from
      Catalonia (Second Wave, Panel of Families and Children) (2006-2010). Separate
      logistic regression models are run for women (n = 1,459) and men (n = 1,105) to
      assess whether negative mood states (self-perceived) are associated with heavy
      episodic drinking measured as binge drinking at least twice a month or more in
      the last year. It is estimated to what extent these effects are attributable to
      familial factors. RESULTS: Feelings of sadness are associated with binge drinking
      among male adolescents (OR 2.7). Feeling pressured by parents keeps also a
      positive association with binge drinking among both sexes (OR 1.8 for males and
      OR 2.1 for women). Women from low-middle and high income groups are more likely
      to engage in binge drinking (OR 1.6 and OR, 1.7 respectively). Migrant family
      background (OR 0.4) and parental control of arrival home on weekend (OR 0.6) are
      negatively related to binge drinking among female adolescents. CONCLUSIONS:
      Negative mood states are associated with heavy episodic drinking. Socio-economic
      and family factors have stronger effect on women than on men.

PMID- 22991034
TI  - [Variables associated with the use of dental services among preschool population
      in Spain: a national health survey analysis].
AB  - BACKGROUND: oral health is integral to health from the eruption of the first
      tooth. To achieving, it is necessary an early establishment of healthy oral
      habits as regular dental checkups. In developed countries, caries is the most
      prevalent chronic pediatric disease and it may be increasing in preschool age.
      OBJECTIVES: a) assessing prevalence of oral health services use among Spanish
      preschool population, b) quantifying and analyzing the existence of variability
      among autonomous community and c) identifying variables associated with such use.
      METHODS: cross-sectional study about Spanish National health Survey (2006).
      SAMPLE: 2,172 children aged between 2 and 5 years (both inclusive). DEPENDENT
      VARIABLE: have gone to dental services at least once during life. INDEPENDENT
      VARIABLES: sociodemographic, self-referred dental health, habits and family
      socioeconomic status variables. Multivariate logistic regression analysis.
      RESULTS: 20.8% of Spanish preschoolers reported had attended dental services.
      Probability of use increased with age (OR: 1,88; IC:1,53-2,31), frequency of
      daily tooth brushing (three or more times per day vrs less than once: OR: 2,94;
      IC: 1,47-5,87) and presence of caries (OR: 2,60; IC: 1,22-5,51). There is a
      socioeconomic gradient about probability of use: it increased with family
      socioeconomic status measured by social class (low vrs high: OR: 0,41; IC: 0,19
      0,86) and maternal educational level (OR: 1,62; IC: 1,13-2,32). There was not
      variability in the oral health services use attributable to the autonomous
      community. CONCLUSIONS: the use of dental health services among Spanish preschool
      population is lower than desirable. The promotion of its use should be
      intensified in children from disadvantaged families.

PMID- 22991035
TI  - Estimating the biodegradation of pesticide in soils by monitoring pesticide
      degrading gene expression.
AB  - Assessing in situ microbial abilities of soils to degrade pesticides is of great
      interest giving insight in soil filtering capability, which is a key ecosystem
      function limiting pollution of groundwater. Quantification of pesticide-degrading
      gene expression by reverse transcription quantitative PCR (RT-qPCR) was tested as
      a suitable indicator to monitor pesticide biodegradation performances in soil.
      RNA extraction protocol was optimized to enhance the yield and quality of RNA
      recovered from soil samples to perform RT-qPCR assays. As a model, the activity
      of atrazine-degrading communities was monitored using RT-qPCRs to estimate the
      level of expression of atzD in five agricultural soils showing different atrazine
      mineralization abilities. Interestingly, the relative abundance of atzD mRNA copy
      numbers was positively correlated to the maximum rate and to the maximal amount
      of atrazine mineralized. Our findings indicate that the quantification of
      pesticide-degrading gene expression may be suitable to assess biodegradation
      performance in soil and monitor natural attenuation of pesticide.

PMID- 22991036
TI  - The origin of isotope-induced helical-sense bias in supramolecular polymers of
      benzene-1,3,5-tricarboxamides.
AB  - The molecular origin of the isotope-induced diastereomeric enrichment in helical
      supramolecular polymers consisting of trialkylbenzene-1,3,5-tricarboxamides
      (BTAs) is studied using plane-wave DFT calculations. We demonstrate that the
      creation of a chiral center at the alpha-position of the alkyl chains of a BTA by
      H-D exchange leads to a small but notable preference for the formation of
      supramolecular hydrogen bonded structures with a particular helicity. The bias
      for one helical sense preference is caused by the orientation of the vibrational
      eigenmodes of the C-H and C-D stretching frequencies at the chiral center and by
      hyperconjugative destabilization of the anti C-H orbital.

PMID- 22991037
TI  - Manipulation of DNA damage checkpoint signaling in cancer cells by antioxidant
      biofactor (AOB).
AB  - Antioxidant biofactor (AOB) is one of the fermented grain food supplements
      commercially available in Japan and other countries. Herein, we investigated the
      effect of AOB on the UVC (254 nm) induced DNA damage in A549 cells. Both
      distilled water and MeOH extracts of AOB did not show any significant cell
      toxicity. However, the UV (25-75 J m(-2)) induced cell death was amplified in the
      presence of these extracts, especially the MeOH extract. When the DNA damage was
      evaluated by comet assay, the AOB water extract prevented the UV induced DNA
      damage at the initial stage but significantly inhibited the repair process,
      especially in the cells exposed to a high dose of UV. The retardation of DNA
      repair was significantly higher in the presence of the MeOH extract,
      concentrating such components as caffeine and polyphenols, and thus the damage
      was enhanced both in the cells irradiated by low and high doses of UV. The DNA
      damage profile was consistent with the inhibitory profile of ATR, a key kinase of
      DNA damage checkpoint signaling. The AOB MeOH extract markedly reduced the
      phosphorylation level of the checkpoint proteins activated by UV, such as p53,
      SMC1 and Chk1, together with ATR. The inhibitory effect of the AOB water extract
      was less effective as compared to the MeOH extract, but was dose-dependent both
      in the cells irradiated with high and low doses of UV. The dual role of AOB as an
      antioxidant and a checkpoint modulator suggests its beneficial use in
      complementary medicine as a potential sensitizer of anticancer treatment.

PMID- 22991039
TI  - Modulation of translation and induction of autophagy by bacterial exoproducts.
AB  - Autophagy is a catabolic process of paramount importance for cellular homeostasis
      during starvation. Generally, autophagy and translation are inversely regulated.
      Many kinds of stress lead to attenuation of translation via phosphorylation of
      eukaryotic translation initiation factor alpha (eIF2alpha). This response is
      conserved from yeast to man and can be either protective or detrimental depending
      on strength and duration of stress, and additional factors. During starvation or
      viral infection, phosphorylation of eIF2alpha is required for induction of
      autophagy. As exemplified here by alpha-hemolysin, a small pore-forming toxin
      (PFT) of Staphylococcus aureus and (S)-3-oxo-C12-homoserine lactone [(S)-3-oxo
      C12-HSL], a quorum-sensing hormone of Pseudomonas aeruginosa, bacterial
      exoproducts may also impact translation and autophagy. Thereby, PFT and (S)-3-oxo
      C12-HSL act differentially. Damage of the plasma membrane by PFT causes efflux of
      potassium, which leads to amino acid starvation and energy loss. This triggers
      amino acid-sensitive eIF2alpha-kinase GCN2, as well as energy sensor AMPK, and
      deactivates mTORC1. The output of this response, that is, transient metabolic
      reprogramming is an essential part of a defense program which enables cells to
      survive attack by a pore-forming agent. Thus, nutrient/energy sensors serve as
      sentinels of plasma membrane integrity. In contrast to PFT, (S)-3-oxo-C12-HSL
      does not cause acute loss of ATP or activation of GCN2, but also triggers
      phosphorylation of eIF2alpha and inhibits translation. This response appears not
      to depend on efflux of potassium and requires eIF2alpha-kinase PKR. Like alpha
      toxin, (S)-3-oxo-C12-HSL increases lipidation of LC3 and accumulation of
      autophagosomes in cells. Apart from directly affecting host-cell viability,
      bacterial exoproducts might galvanize bystander cells to prepare for close combat
      with microbial offenders or inadvertently accommodate some of them.

PMID- 22991040
TI  - Viral latency drives 'memory inflation': a unifying hypothesis linking two
      hallmarks of cytomegalovirus infection.
AB  - Low public awareness of cytomegalovirus (CMV) results from the only mild and
      transient symptoms that it causes in the healthy immunocompetent host, so that
      primary infection usually goes unnoticed. The virus is not cleared, however, but
      stays for the lifetime of the host in a non-infectious, replicatively dormant
      state known as 'viral latency'. Medical interest in CMV results from the fact
      that latent virus can reactivate to cytopathogenic, tissue-destructive infection
      causing life-threatening end-organ disease in immunocompromised recipients of
      solid organ transplantation (SOT) or hematopoietic cell transplantation (HCT). It
      is becoming increasingly clear that CMV latency is not a static state in which
      the viral genome is silenced at all its genetic loci making the latent virus
      immunologically invisible, but rather is a dynamic state characterized by
      stochastic episodes of transient viral gene desilencing. This gene expression can
      lead to the presentation of antigenic peptides encoded by 'antigenicity
      determining transcripts expressed in latency (ADTELs)' sensed by tissue
      patrolling effector-memory CD8 T cells for immune surveillance of latency [In
      Reddehase et al., Murine model of cytomegalovirus latency and reactivation,
      Current Topics in Microbiology and Immunology, vol 325. Springer, Berlin, pp 315
      331, 2008]. A hallmark of the CD8 T cell response to CMV is the observation that
      with increasing time during latency, CD8 T cells specific for certain viral
      epitopes increase in numbers, a phenomenon that has gained much attention in
      recent years and is known under the catchphrase 'memory inflation.' Here, we
      provide a unifying hypothesis linking stochastic viral gene desilencing during
      latency to 'memory inflation.'

PMID- 22991041
TI  - Targeting high density lipoproteins in the prevention of cardiovascular disease?
AB  - Recent studies involving HDL-raising therapeutics have greatly changed our
      understanding of this field. Despite effectively raising HDL-C levels, niacin
      remains of uncertain clinical benefit. Synthetic niacin receptor agonists are
      unlikely to raise HDL-C or have other beneficial effects on plasma lipids.
      Despite the failure in phase 3 of 2 CETP inhibitors, 2 potent CETP inhibitors
      that raise HDL-C levels by >100 % (and reduce LDL-C substantially) are in late
      stage clinical development. Infusions of recombinant HDL containing 'wild-type'
      apoA-I or apoA-I Milano, as well as autologous delipidated HDL, all demonstrated
      promising early results, and remain in clinical development. A small molecule
      that causes upregulation of endogenous apoA-I production is also in clinical
      development. Finally, upregulation of macrophage cholesterol efflux pathways
      through agonism of liver X receptors or antagonism of miR-33 remains of
      substantial interest. The field of HDL therapeutics is poised to transition from
      the 'HDL-cholesterol hypothesis' to the 'HDL flux hypothesis' in which the impact
      on flux from macrophage to feces is deemed to be of greater therapeutic benefit
      than the increase in steady-state concentrations of HDL cholesterol.

PMID- 22991042
TI  - The role of ethanol on the anticonvulsant effect of valproic acid and cortical
      microvascular changes after epileptogenesis in mice.
AB  - There have been conflicting reports regarding the role of ethanol in seizure.
      Another effect of ethanol is vascular damage in cerebral tissue. This study
      investigates the influence of ethanol on antiepileptic efficacy of valproic acid
      (VPA) and cerebral microvascular structure. In this study, four groups of mice
      (25-30 g) received pentylenetetrazole (PTZ) i.p. (37 mg/kg) every other day.
      Different groups of animals received an injection of saline, ethanol (1 g/kg),
      VPA (100 mg/kg), or VPA and ethanol 30 min before PTZ. Animals in groups 5 and 6
      received only ethanol and saline, respectively. After recording seizure
      parameters, the animals were sacrificed under deep anesthesia and the brains of
      the animals were removed and fixed, thereafter coronal sections were prepared
      from cerebral cortex. Then, the cerebral microvessels were counted in microscopic
      sections after hematoxylin-eosin staining. Ethanol injection (1 g/kg) for 7 days
      decreased stage 4 duration and increased latency to the onset of stage 1 and
      stage 4 of seizure (p < 0.001). Concomitant injection of VPA (5 min before
      ethanol) and ethanol had significantly stronger anticonvulsant effects than VPA
      alone (p < 0.001). Furthermore, the findings showed that not only the cerebral
      microvessels increased significantly in ethanol group compared with saline group
      (p < 0.05), but also there were morphological changes in vascular endothelium in
      ethanol group. The obtained results show that short-term ethanol administration
      has anticonvulsant effects along with VPA, and enhances the anticonvulsant
      effects of VPA. Furthermore, it is possible that VPA leads to decreased ethanol
      induced vascular damage.

PMID- 22991043
TI  - Analytic information processing style in migraineurs.
AB  - Despite great advances in pathophysiological facets of migraine that have been
      made during recent years, as of today, migraine etiology is still not completely
      understood; moreover, to date the relationship between psychological factors and
      this primary headache must be further elucidated. However, abnormal information
      processing, as measured by evoked and event-related potentials, has been
      considered a key feature in migraine pathogenesis. The aim of this work was to
      study the relationships between analytic/global style of information processing
      and migraine, hypothesizing an analytic style, as highlighted by our previous
      study on cluster headache. This study applied three cognitive style tests never
      previously used in the context of migraine: "Sternberg-Wagner Self-Assessment
      Inventory", the C. Cornoldi test series called AMOS, and Brain-Dominance
      Questionnaire. 280 migraneurs with and without aura were tested and matched with
      two control groups: healthy subjects and tension-type headache patients. Our
      results demonstrated a strong correlation between analytic information processing
      style and migraine, indicating a preference toward a visual sensory approach in
      migraine without aura, in line with known neuroelectrophysiological data. These
      findings may suggest a role for this specific cognitive behavior in migraine
      pathogenesis, leading us to further investigate the neuroelectrophysiological,
      neurobiological, and epigenetic correlates. 

PMID- 22991044
TI  - Channeling headache: novel findings in the study of Ca(2+)-channels and FHM-1.
AB  - Familial hemiplegic migraine type 1 (FMH-1) is a rare form of migraine with aura,
      which is characterized by transient hemiparesis, sensory loss and visual
      disturbances. This monogenic disease shares many common features with classic
      migraine, suggesting a similar molecular pathophysiology. Migraine is triggered
      by activation and sensitization of the trigeminovascular system, specifically the
      trigeminal nociceptive afferents innervating the meninges. Aura migraine is
      associated with cortical spreading depression (CSD), which is a short-lasting
      intense wave of neuronal and glial cell depolarization that slowly progresses
      over the cortex and is followed by long-lasting neuronal activity depression.

PMID- 22991045
TI  - The developmental basis of visuomotor capabilities and the causal nature of motor
      clumsiness to cognitive and empathic dysfunction.
AB  - Motor disorders are a prominent feature of several psychiatric conditions
      including autism and schizophrenia. The paper extends the idea of a causal
      association between motor feedback and the cognitive character of the brain.
      First, it elaborates a detailed theory of how motor function and visual
      transformations are encoded as a cortical algorithm. The mechanism of motor
      efference copy is proposed for all forms of cognitive development. A special case
      of a component theory of efference copy is reconsidered with regards to the
      dorsal stream property of spatial awareness, in addition to its role in the
      formulation of motor repertoires. The spatial component of awareness within any
      and all sensory modalities, including proprioception itself, is compromised by
      the failed cerebellar contribution. This does not mean the peripheral
      proprioceptive signal is defective. Rather, it's an aberrant capacity of a
      predictive cerebellar-mediated reafference. Normally considered a feedforward
      output for changes in the positions of joints as part of a planned action, the
      proposal is for the consequences of those actions to categorize cortical networks
      as a feedback copy. This leads directly to higher level disorders of attention,
      theory of mind, and ultimately empathic insights by autistic subjects. Cognition
      and empathy are embodied by the process of active exploration of an organism and
      are dependent on the integrity of structures subserving aspects of motor
      behaviour. The main focus here is the cerebellum, an organ writ large in the
      pathophysiology of autism. What autism teaches us is that empathy is a construct
      of spatial awareness.

PMID- 22991046
TI  - State-independent intracellular access of quaternary ammonium blockers to the
      pore of TREK-1.
AB  - We previously reported that TREK-1 gating by internal pH and pressure occurs
      close to or within the selectivity filter. These conclusions were based upon
      kinetic measurements of high-affinity block by quaternary ammonium (QA) ions that
      appeared to exhibit state-independent accessibility to their binding site within
      the pore. Intriguingly, recent crystal structures of two related K2P potassium
      channels were also both found to be open at the helix bundle crossing. However,
      this did not exclude the possibility of gating at the bundle crossing and it was
      suggested that side-fenestrations within these structures might allow state
      independent access of QA ions to their binding site. In this addendum to our
      original study we demonstrate that even hydrophobic QA ions do not access the
      TREK-1 pore via these fenestrations. Furthermore, by using a chemically reactive
      QA ion immobilized within the pore via covalent cysteine modification we provide
      additional evidence that the QA binding site remains accessible to the cytoplasm
      in the closed state. These results support models of K2P channel gating which
      occur close to or within the selectivity filter and do not involve closure at the
      helix bundle crossing.

PMID- 22991047
TI  - Mycobacterium avium serovars 2 and 8 infections elicit unique activation of the
      host macrophage immune responses.
AB  - Mycobacterium avium is an opportunistic pathogen whose pathogenesis is attributed
      to its serovar-specific glycopeptidolipid (ssGPL), which varies among its 31
      serovars. To determine if the presence and type of ssGPLs contribute to M. avium
      pathogenesis, we infected murine macrophages (mphis) with two M. avium wild type
      (wt) serovars (2 and 8) and their serovar-null strains. We examined the influence
      of ssGPL (presence and type) on cytokine production in non-activated (-IFN-gamma)
      and activated (+IFN-gamma) mphis, and the bacterial intra-mphi survival over a 6
      day infection process. Serovar-2 infections activated TNF-alpha production that
      increased over the 6 day period and was capable of controlling the intra-mphi
      serovar-2 null strain. In contrast, the serovar-8 infection stimulated a strong
      pro-inflammatory response, but was incapable of removing the invading pathogen,
      maybe through IL-10 production. It was clear that the intracellular growth of
      serovar-null in contrast to the wt M. avium strains was easily controlled. Based
      on our findings and the undisputed fact that M. avium ssGPL is key to its
      pathogenesis, we conclude that it is not appropriate to dissect the pathogenesis
      of one M. avium serovar and apply those findings to other serovars.

PMID- 22991048
TI  - Apps of steel: are exercise apps providing consumers with realistic
      expectations?: a content analysis of exercise apps for presence of behavior
      change theory.
AB  - OBJECTIVE: To quantify the presence of health behavior theory constructs in
      iPhone apps targeting physical activity. METHODS: This study used a content
      analysis of 127 apps from Apple's (App Store) Health & Fitness category. Coders
      downloaded the apps and then used an established theory-based instrument to rate
      each app's inclusion of theoretical constructs from prominent behavior change
      theories. Five common items were used to measure 20 theoretical constructs, for a
      total of 100 items. A theory score was calculated for each app. Multiple
      regression analysis was used to identify factors associated with higher theory
      scores. RESULTS: Apps were generally observed to be lacking in theoretical
      content. Theory scores ranged from 1 to 28 on a 100-point scale. The health
      belief model was the most prevalent theory, accounting for 32% of all constructs.
      Regression analyses indicated that higher priced apps and apps that addressed a
      broader activity spectrum were associated with higher total theory scores.
      CONCLUSION: It is not unexpected that apps contained only minimal theoretical
      content, given that app developers come from a variety of backgrounds and many
      are not trained in the application of health behavior theory. The relationship
      between price and theory score corroborates research indicating that higher
      quality apps are more expensive. There is an opportunity for health and behavior
      change experts to partner with app developers to incorporate behavior change
      theories into the development of apps. These future collaborations between health
      behavior change experts and app developers could foster apps superior in both
      theory and programming possibly resulting in better health outcomes.

PMID- 22991049
TI  - Patient-Centered Care: Depends on  the Point of View.

PMID- 22991051
TI  - Development of a multilevel intervention to increase HIV clinical trial
      participation among rural minorities.
AB  - Minorities are disproportionately affected by HIV/AIDS in the rural Southeast;
      therefore, it is important to develop targeted, culturally appropriate
      interventions to support rural minority participation in HIV/AIDS research. Using
      intervention mapping, we developed a comprehensive multilevel intervention for
      service providers (SPs) and people living with HIV/AIDS (PLWHA). The authors
      collected data from both groups through 11 focus groups and 35 individual
      interviews. Resultant data were used to develop matrices of behavioral outcomes,
      performance objectives, and learning objectives. Each performance objective was
      mapped with changeable, theory-based determinants to inform components of the
      intervention. Behavioral outcomes for the intervention included the following:
      (a) eligible PLWHA will enroll in clinical trials and (2) SPs will refer eligible
      PLWHA to clinical trials. The ensuing intervention consists of four SPs and six
      PLWHA educational sessions. Its contents, methods, and strategies were grounded
      in the theory of reasoned action, social cognitive theory, and the concept of
      social support. All materials were pretested and refined for content
      appropriateness and effectiveness.

PMID- 22991050
TI  - Men's and women's health beliefs differentially predict coronary heart disease
      incidence in a population-based sample.
AB  - OBJECTIVE: To examine gender differences in the association between beliefs in
      heart disease preventability and 10-year incidence of coronary heart disease
      (CHD) in a population-based sample. METHODS: A total of 2,688
      Noninstitutionalized Nova Scotians without prior CHD enrolled in the Nova Scotia
      Health Study (NSHS95) and were followed for 10 years. Risk factors, health
      behaviors, and incident CHD were assessed. Participants responded "yes" or "no"
      to a question about heart disease preventability. Survival models, adjusted for
      age, income, total and high-density lipoprotein cholesterol, and systolic blood
      pressure, were used to estimate the relation between health belief and incident
      CHD. Gender differences in the relation between health beliefs and health
      behaviors were assessed. RESULTS: Gender was a significant moderator of the
      relation between belief and CHD incidence; specifically, women who believed heart
      disease could be prevented were less likely to have incident CHD events compared
      with women who believed heart disease could not be prevented (hazard ratio [HR] =
      0.36, 95% confidence interval [CI] = 0.24-0.55, p < .001). This relation was not
      found for men. Belief was also related to smoking behavior for women (beta = 
      0.70, odds ratio [OR] = 0.50, 95% CI = 0.33-0.74, p = .001) but not for men.
      Smoking significantly mediated the relation between health beliefs and incident
      CHD for women (z = -1.96, p = .05), but not for men. CONCLUSION: Health belief in
      prevention and subsequent smoking was an important independent predictor of
      incident CHD in women but not in men.

PMID- 22991052
TI  - Probing the molecular mechanisms for pristinamycin yield enhancement in
      Streptomyces pristinaespiralis.
AB  - The mechanisms for the enhancement of pristinamycin production in the high
      yielding recombinants of Streptomyces pristinaespiralis obtained by genome
      shuffling were investigated by quantitative real-time PCR (Q-PCR) and amplified
      fragment length polymorphism (AFLP) techniques. Q-PCR analysis showed that snaB
      and snbA involved, respectively, in the biosynthesis of pristinamycins II and I
      component had more extended high expression in the recombinant than that in the
      ancestor during fermentation process, indicating their expression changes might
      be key factors during the biosynthesis of the antibiotic. In addition, the
      antecedent establishment of the high self-resistance to pristinamycin, because
      ptr resistance gene started high-level expression ahead of the onset of the
      antibiotic production in the recombinant, might also lead to the increase of the
      antibiotics yield. AFLP analysis of these recombinants revealed genome variation
      of two novel genes, the homologs of AfsR regulatory gene and transposase gene,
      indicating these two gene variations were probably responsible for yield
      improvement of pristinamycin. This study provided several potential molecular
      clues for pristinamycin yield enhancement.

PMID- 22991053
TI  - Cisterna magna width at 11-13 weeks in the detection of posterior fossa
      anomalies.
AB  - OBJECTIVE: To construct reference ranges for cisterna magna (CM) width at 11-13
      weeks' gestation in healthy fetuses and determine whether open spina bifida and
      posterior fossa anomalies could be diagnosed in the first trimester. METHODS:
      This was a retrospective study. CM width reference ranges were constructed based
      on the measurements obtained from 80 healthy fetuses with normal postnatal
      outcome undergoing routine first-trimester ultrasound at 11-13 weeks, using the
      Lambda-Mu-Sigma method. CM was measured in the fetal mid-sagittal view, as
      routinely used for nuchal translucency assessment. In addition, first-trimester
      ultrasound images in 11 fetuses with open spina bifida or posterior fossa
      anomalies, most of which were diagnosed later in pregnancy, were retrospectively
      reviewed, and CM measurements were compared against reference ranges. RESULTS: CM
      width was noted to increase with gestational age in normal fetuses. The anomalies
      in the 11 fetuses we reviewed were: open spina bifida (n = 5), megacisterna magna
      (n = 3), Blake's pouch cyst (n = 2) and posterior fossa arachnoid cyst (n = 1).
      All fetuses with open spina bifida had a CM width below the 5(th) percentile. In
      the two fetuses with Blake's pouch cyst and in two with megacisterna magna, CM
      width was above the 95(th) percentile. In one of the fetuses with a megacisterna
      magna and the one with an arachnoid cyst, CM width was within normal range.
      CONCLUSION: We have constructed reference ranges for CM width at 11-13 weeks
      using the mid-sagittal view. It appears that first-trimester CM width can be used
      as a marker for the early detection of open spina bifida. However, our findings
      need to be confirmed in prospective large series.

PMID- 22991054
TI  - Endoscopic cricopharyngeal myotomy for management of cricopharyngeal achalasia
      (CA) in an 18-month-old child.
AB  - A 6-month-old patient presented with dysphagia and failure to thrive. Video
      fluoroscopic swallow study (VFSS), esophagogastroduodenoscopy, and manometry were
      diagnostic for CA. A gastrostomy tube was placed at 8 months. Botulinum toxin
      injection improved symptoms, but within 10 weeks symptoms returned. At 18 months,
      an uncomplicated endoscopic CPM was performed. A postoperative VFSS demonstrated
      cricopharyngeal bar resolution. Within 3 months, patient was feeding orally
      without a G tube. Pediatric CPA treatment options consist of dilation, botox, and
      transcervical CPM. To our knowledge, this is the youngest patient treated with
      endoscopic CPM. Intraoperative video and photographs are presented.

PMID- 22991055
TI  - [The cost of occupational cancer in Spain].

PMID- 22991056
TI  - [Direct health care costs of lung and bladder cancer attributable to work. Spain,
      2008].
AB  - BACKGROUND: The lack of recognition of the occupational etiology of some
      malignant tumors implies that the cost of their health care rests in the National
      Health System. The aim of our study is to estimate the job-related lung and
      bladder cancer in Spain in 2008 treated by the National Health System (NHS), as
      well as the medical costs derived from its treatment in the same year. METHODS:
      Literature estimates of Attributable Fractions due to work were used to estimate
      the job-related cases treated. Medical costs for specialised care (outpatient and
      hospital admissions) are derived from the NHS cost accounts. Costs due to primary
      health care and pharmaceutical benefits are obtained from secondary sources.
      Figures were computed according to disease and sex. RESULTS: A total of 10,652
      NHS hospital discharges in 2008 were due to lung cancer and bladder cancer
      attributable to work (only 16 were recognized as professional the same year). The
      treatment of these cases cost to the NHS in 2008 almost 88 million euros, of
      which 61.2 million belong to lung cancer and 26.5 to the bladder. CONCLUSIONS:
      The magnitude of lung and bladder cancer attributable to work in Spain is much
      higher than reflected in the official Registry of Occupational Diseases. It
      should be recognized as professional to activate appropriate prevention policies.
      The related health care expenditure, which is financed by the NHS, is quite
      significant.

PMID- 22991057
TI  - [Typology, values and preferences of people with HIV and imaginaries of
      infection: a qualitative research: Spain, 2010].
AB  - BACKGROUND: Therapeutic advance achieved over the last fifteen years in
      addressing HIV and AIDS correlate with changes in the subjective experiences of
      persons with HIV and in the sociocultural imaginary of HIV infection. This paper
      reports findings on two areas: the current typology of HIV patients in the
      Spanish case and the evolution of the perception of HIV among PLWHA. METHODS:
      Qualitative study in eight Spanish cities (October 2010-March 2011). We conducted
      9 focus groups and 30 in-depth interviews with PLWHA of different ages and length
      of treatment, all of them under medical care. Interviews and focus group were
      transcribed and narrative and discursive data were subjected to sociological
      analysis. RESULTS: We suggest a classification of 7 different collectives of
      persons with HIV in the Spanish context, which reflect different historical
      periods in the epidemiology of the infection as well as the evolution of
      treatments and of the experiences of those infected. In recent times there have
      been significant changes in the social system of images associated with HIV,
      which point to an increasingly debilitated image of chronicity and to a decline
      in the perception of its danger to health. CONCLUSIONS: But this new imaginary
      does not distribute equally among all persons with HIV. On the contrary, there is
      a certain polarization of images, essentially between the two sub-groups most
      epidemiologically relevant among newly diagnosed HIV patients in Spain: younger
      men who have sex with men (<30-35 years) and immigrants.

PMID- 22991058
TI  - [Premature mortality excess related to influenza in Spain during an interpandemic
      period].
AB  - BACKGROUND: The indicator of Potential Years of Life Lost (PYLL) has been
      frequently used to analysis of premature mortality and recently has been used to
      estimate the impact of the last influenza A(H1N1)pdm09 pandemic. The aim of this
      study was to estimate the excess deaths from pneumonia and influenza (P&I) in
      Spain and the PYLL during the period 1980-2008, measuring the mortality
      attributable to influenza regarding the type/subtype of influenza dominant in
      each season. METHODS: Monthly excess deaths were calculated with cyclical
      regression models. The PYLL calculation was performed as the product of the
      number of excess deaths and the difference between life expectancy at birth and
      years lived for each age group. The analysis of the variation between P&I excess
      deaths and PYLL, depending on the predominant influenza virus type/subtype was
      carried out with a Poisson regression analysis. RESULTS: In seasons dominated by
      influenza virus A(H3) the average P&I excess deaths was estimated at 1,348, and
      for PYLL in 5.297, while in seasons dominated by A(H1) or B the average P&I
      excess deaths was 648, and for PYLL 2.885. The adjusted rate ratios of excess
      (2.11, CI-95%=2.05-2.16) and PYLL (1.86, CI-95%=1.83-1.88) indicate that the
      relative frequencies for both indicators are significantly larger in seasons
      dominated by influenza virus A(H3). CONCLUSIONS: Excess deaths and PYLL doubled
      when comparing seasons predominantly subtype A(H3) and other influenza viruses.

PMID- 22991059
TI  - [Cost-effectiveness analysis of maintenance therapy with rituximab in patients
      with follicular lymphoma responding to induction therapy at the first line].
AB  - BACKGROUND: Maintenance therapy with rituximab for follicular lymphoma (FL)
      responding to induction at the first-line, significantly increases progression
      free survival compared with observation. To estimate the efficiency of this
      therapeutic option, we performed a cost-effectiveness analysis of maintenance
      therapy of the follicular lymphoma (FL) that responds to induction in first line,
      with rituximab, compared with the option of "watch and wait" strategy. METHODS:
      We did a Markov model of the FL, with four health states (progression free
      survival in first or second line, progression and death). The transition
      probabilities between states were obtained from clinical trials PRIMA and EORTC
      20981. Health state utilities were obtained from literature. The use of health
      resources, from the perspective of the National Health System was estimated by a
      panel of Spanish clinical experts. Unit costs (euros in 2011) were obtained from
      Spanish sources. Deterministic and probabilistic analyses were made. RESULTS: In
      the deterministic base case analysis, for a time horizon of 30 years, the cost
      per life year gained (LYG) and quality-adjusted life-years (QALYs) gained, was
      euros 5,663 and euros 6,253 respectively. The sensitivity analyses confirmed the
      stability of the base case for time horizons of 10 and 20 years and various
      statistical distributions (Weibull, exponential, log-logistic, log-normal,
      Gompertz, and gamma) ranging between euros 4,222 and euros 8,766. Rituximab
      maintenance is cost-effective from a time horizon of 5.7 years (cost per QALY
      gained of euros 29,998). CONCLUSION: Compared with observation, rituximab
      maintenance treatment of the FL that responds to induction therapy in first line,
      is cost-effective according to the present model.

PMID- 22991060
TI  - [Prevalence of tobacco consumption among working population after the law
      42/2010, Spain].
AB  - BACKGROUND: The aim of this study was to analyze the impact on tobacco
      consumption among working population of the Law 42/2010, which amends smoking
      regulations in Spain. METHODS: Data were obtained from 413,473 Occupational
      Health check-ups, conducted between July of 2009 and June of 2011, in the Society
      for Prevention of a Mutual Insurance Company. We analyzed changes in the biannual
      percentage of smokers and the magnitude of tobacco consumption among smokers in
      the overall set of medical check-ups, by gender, age, occupational level (manual
      vs. non-manual workers), and in the specific occupational subgroup of waiters,
      barmen and similar workers (chi-square test). RESULTS: In the overall set of
      medical check-ups, the percentage of smokers decreased by 5% (from 40.3% to
      35.3%) over the period of study (p <0.001) and the group of smokers with lower
      daily consumption (< 10 cigarettes) became the most frequent (p <0.001). In the
      group of waiters, barmen and similar workers the differences in the biannual
      percentage of smokers did not reach statistical significance (p =0.07). In this
      group, smokers of < 10 cigarretes/ day also became the most common consumption
      group (increasing from 40.5% to 48.8%) and the percentage of 21-40 cigarretes/day
      decreased from 10.6% to 4% (p =0.008). CONCLUSIONS: These results suggest that
      the new regulation has been accompanied by a significant reduction in smoking
      among Spanish workers and strongly support population-level measures against
      tobacco consumption.

PMID- 22991061
TI  - [Indicated prevention of problematic drug consumption in adolescents of
      barcelona, Spain].
AB  - BACKGROUND: The Drugs Advice Service (SOD in its Catalan acronym) in Barcelona
      (Catalonia, Spain) provides an Information and Guidance Program (IGP) for
      teenagers, and an Alternative Measures Program (AMP) targeting minors fined for
      consumption / possession of illegal drugs in public spaces. This study describes
      these programs and compares the profiles of their users. METHODS: Cross-sectional
      descriptive study of 1,010 people discharged from the two SOD programs in 2008-10
      after screening for psychiatric disorders and addiction and an extended brief
      intervention for subjects without pathology. The profiles of the users were
      compared, and age-specific rates of AMP use were calculated. RESULTS: Cannabis
      causes 89.9% of entries in the SOD. The proportion of IGP users with high risk
      criteria for cannabis is 13.3% and with risk for alcohol 11.3%, while in AMP it
      is 8.9%, and 4%. Criteria for substance dependence or abuse or another
      psychiatric disorder caused referral of 6% of AMP users and 38% of IGP users.
      CONCLUSIONS: Adolescents in the AMP had a pattern of cannabis use (and often of
      alcohol) of low or moderate risk, compared to IGP. Beyond the value of the
      indicated prevention intervention, the programmes facilitate the early detection
      and referral of problematic substance use and mental disorders in early stages.

PMID- 22991062
TI  - [Behavioral disorders prevalence in pediatrics primary care: region of Valencia,
      Spain, 2009].
AB  - BACKGROUND: Childhood and adolescence mental health needs a proper monitoring.
      The aim is to estimate behavioral disorders prevalence in paediatric primary care
      in the Region of Valencia (Spain) and to describe its distribution according to
      sex, age and impact areas. METHODS: Cross-sectional research. Region of
      Valencia's Health Surveillance Network observed along 2009 the behavioral
      disorders in patients primary health care between 3 and 14 years old. Prevalence
      and confidence intervals at 95% were calculated. Chi-square test (p<0,05) was
      calculated to explore the differences in behavioral disorders according to sex,
      age and impact areas. RESULTS: Total cases notified were 626. Out of participants
      70% were boys. The estimate overall prevalence for the population between 3-14
      years old was 351 per 10.000 (IC95%: 330-372), 491(IC95%:456-525) in boys and 202
      (IC95%:179-226) in girls. Hyperactivity was the highest prevalence (85 per
      10.000, CI: 74-95). The 7-10 age grup years old had the highest prevalence (428
      per 10.000, IC95%:367-489). The impact in the family was 69,4% in boys and 65,9%
      in girls (p<0,5). CONCLUSIONS: The Behavioral Disorders prevalence found in
      paediatrics patients in primary care was important, showed different
      epidemiologic profile as function of age and sex, and proved the family was the
      principal impact area.

PMID- 22991064
TI  - Hemimegalencephaly associated with congenital infiltrating lipomatosis of the
      face: a case report.
AB  - Hemimegalencephaly (HME) is a rare congenital malformation of the brain, grossly
      characterized by enlargement and overdevelopment of one cerebral hemisphere. We
      describe a 16-month-old patient with facial asymmetry caused by congenital
      infiltrating lipomatosis of the face (CILF) associated with ipsilateral HME.
      Although HME has been described as part of different syndromic diseases, the
      association of HME with CILF has been rarely reported. Our case and literature
      review suggest that when the diagnosis of CILF is suspected or established, the
      possible presence of associated HME has to be considered and a magnetic resonance
      imaging (MRI) must be performed even in absence of neurological features, not
      always present in early stages. MRI also demonstrates the involvement of
      intracranial structures outside the affected cerebral hemisphere, such as brain
      stem, cerebellum, cranial nerves, and blood vessels. In our patient, computed
      tomography of the brain provided detailed information on osseous hypertrophy and
      skull-base foramina enlargement.

PMID- 22991065
TI  - Role of cytokines in experimentally induced lung cancer and chemoprevention by
      COX-2 selective inhibitor, etoricoxib.
AB  - This study explored the role of pro- and anti-inflammatory cytokines in dimethyl
      benz(a)anthracene (DMBA)-induced lung cancer and its subsequent correction with a
      COX-2 inhibitory NSAID, etoricoxib. A single dose of DMBA (20 mg/kg body weight)
      in 0.9 % NaCl administered intratracheally was used to induce tumors in the rat
      lungs in 20 weeks. The study of pro-inflammatory cytokines like IL-1beta, TNF
      alpha, and IFN-gamma revealed their upregulation by DMBA administration and
      restoration of their levels toward normal by the treatment with etoricoxib, while
      the anti-inflammatory cytokine IL-2 was found to be down-regulated with
      carcinogen administration and corrected with etoricoxib treatment. Apoptosis was
      studied by mitochondrial Bcl-2/Bax ratio and staining with fluorescent dyes
      acridine orange/ethidium bromide. The results showed a decreased apoptotic level
      with DMBA which was corrected with etoricoxib. Also, mitochondrial membrane
      potential was studied using JC-1 and rhodamine-123, which are membrane permeant
      fluorescent dyes, and generate information about cells at lower and higher
      mitochondrial membrane potential (?Psi(M)). The results showed the presence of
      maximum number of cells with higher ?Psi(M) in the DMBA group and their number
      was considerably lowered in the other three groups.

PMID- 22991063
TI  - Metallation and mismetallation of iron and manganese proteins in vitro and in
      vivo: the class I ribonucleotide reductases as a case study.
AB  - How cells ensure correct metallation of a given protein and whether a degree of
      promiscuity in metal binding has evolved are largely unanswered questions. In a
      classic case, iron- and manganese-dependent superoxide dismutases (SODs) catalyze
      the disproportionation of superoxide using highly similar protein scaffolds and
      nearly identical active sites. However, most of these enzymes are active with
      only one metal, although both metals can bind in vitro and in vivo. Iron(ii) and
      manganese(ii) bind weakly to most proteins and possess similar coordination
      preferences. Their distinct redox properties suggest that they are unlikely to be
      interchangeable in biological systems except when they function in Lewis acid
      catalytic roles, yet recent work suggests this is not always the case. This
      review summarizes the diversity of ways in which iron and manganese are
      substituted in similar or identical protein frameworks. As models, we discuss (1)
      enzymes, such as epimerases, thought to use Fe(II) as a Lewis acid under normal
      growth conditions but which switch to Mn(II) under oxidative stress; (2)
      extradiol dioxygenases, which have been found to use both Fe(II) and Mn(II), the
      redox role of which in catalysis remains to be elucidated; (3) SODs, which use
      redox chemistry and are generally metal-specific; and (4) the class I
      ribonucleotide reductases (RNRs), which have evolved unique biosynthetic pathways
      to control metallation. The primary focus is the class Ib RNRs, which can
      catalyze formation of a stable radical on a tyrosine residue in their beta2
      subunits using either a di-iron or a recently characterized dimanganese cofactor.
      The physiological roles of enzymes that can switch between iron and manganese
      cofactors are discussed, as are insights obtained from the studies of many groups
      regarding iron and manganese homeostasis and the divergent and convergent
      strategies organisms use for control of protein metallation. We propose that, in
      many of the systems discussed, "discrimination" between metals is not performed
      by the protein itself, but it is instead determined by the environment in which
      the protein is expressed.

PMID- 22991067
TI  - Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops
      fetalis.
AB  - OBJECTIVE: Nonimmune hydrops fetalis (NIHF) is defined by the excessive fluid
      accumulation in more than one foetal compartments and body cavities because of
      nonimmune reasons. It has been described that 14 lysosomal diseases may be
      causative of NIHF. The aim of this study was to design a fast protocol to
      investigate the most frequent lysosomal diseases that are reported that may cause
      NIHF. METHOD: We analysed the glycosaminoglycans excretion in the amniotic fluid
      supernatant and four different lysosomal enzymatic activities in the amniotic
      cultured cells of the different NIHF amniotic fluids we received. RESULTS: We
      investigated 30 NIHF cases, using this fast protocol. We detected two cases of
      NIHF because of lysosomal diseases, which represent 6.6%. We diagnosed one case
      of mucopolysaccharidosis type VII and one case of Gaucher disease. CONCLUSION:
      The fast protocol we designed analyses seven of the most frequent lysosomal
      pathologies that have been described that may cause NIHF, with only five
      different determinations, which make the analysis of NIHF fast, cost-effective
      and without need of too much amniotic fluid. We believe this protocol may be
      useful for the analysis of lysosomal diseases in NIHF.

PMID- 22991066
TI  - Vertebral fractures and trabecular microstructure in men with prostate cancer on
      androgen deprivation therapy.
AB  - Androgen deprivation therapy (ADT), a treatment for prostate cancer, is
      associated with bone loss and fractures. Dual-energy X-ray absorptiometry (DXA)
      measured bone mineral density does not assess vertebral fractures (VF). High
      resolution micro-magnetic resonance imaging (HR-MRI) assesses bone
      microarchitecture and provides structural information. To determine if VF
      identification increased the diagnosis of osteoporosis beyond DXA and if HR-MRI
      demonstrated skeletal deterioration in men with VF, we cross-sectionally studied
      137 men aged >= 60 years with nonmetastatic prostate cancer on ADT for >= 6
      months. Vertebral fracture assessment (VFA) by DXA was confirmed with X-rays. HR
      MRI of the wrist included bone volume to total volume (BV/TV), surface density
      (trabecular plates), surface/curve ratio (plates/rods), and erosion index (higher
      depicts deterioration). VF were found in 37% of men; the majority were unknown.
      Seven percent of participants were classified as osteoporotic by hip or spine
      DXA. Thirty-seven percent of men without osteoporosis by DXA had VF identified,
      suggesting that 90% of patients with clinical osteoporosis would have been
      misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV,
      surface density, and spine, hip, and wrist DXA were lower, and erosion index was
      higher in men with moderate-severe VF compared with lesser grades (all p < 0.05).
      By unadjusted ROC analysis, the addition of HR-MRI to DXA at the spine, hip, and
      femoral neck added substantially (AUC increased 0.831 to 0.902, p < 0.05) to
      prediction of moderate-severe vertebral fracture. HR-MRI indices were associated
      with spine, hip, and wrist DXA measures (p < 0.01). Longer duration of ADT was
      associated with lower BV/TV, surface density, and surface/curve ratio (p < 0.05).
      ADT for men with prostate cancer is associated with silent VF. DXA alone leads to
      misclassifications of osteoporosis, which can be avoided by VF assessment. HR-MRI
      provides a novel technique to assess deterioration of structural integrity in men
      with VF and adds micro-structural information.

PMID- 22991068
TI  - MRI quantification of fatty infiltration and muscle atrophy in a mouse model of
      rotator cuff tears.
AB  - Rotator cuff pathology is the most common shoulder problem seen by orthopedic
      surgeons. Rotator cuff muscle fatty infiltration and muscle atrophy are common in
      larger tears and are considered predicting factors for the prognosis of cuff
      repair. Clinically, MRI is the gold standard in determining fatty infiltration
      and muscle atrophy; however, analysis for MRI imaging is primarily qualitative in
      nature with the results lacking further validation. We have recently developed a
      mouse model of rotator cuff tears. The goal of this study is to quantify and
      verify rotator cuff muscle atrophy and fatty infiltration using high-resolution
      MRI in our mouse model. The rotator cuff muscles were analyzed for fat using a
      triglyceride quantification assay (TQA), muscle volume was measured through water
      displacement (WD), and histology. The study revealed that MRI had a high
      correlation with fat as measured with histology and TQA (R(2)  =098). MRI also
      correlated well with atrophy measured with WD and wet weight. This suggests that
      MRI is a reliable modality in evaluating the progression of fatty infiltration
      and muscle atrophy following rotator cuff tears in a small animal model.

PMID- 22991069
TI  - Neurological complications of hepatitis C infection.
AB  - Though well-known as a cause of liver disease, Hepatitis C virus infection is
      emerging as a cause of a variety of peripheral and central nervous system
      disorders. The virus causes chronic persistent infection with complex immune
      responses in the majority of individuals. Viral infection may have the potential
      to generate neurological illness through direct infection of neural cells or
      through immune-mediated mechanisms, including enhancement of autoimmune
      responses. Moreover, the mainstay of antiviral treatment of hepatitis C
      infection, interferon-alpha, is itself associated with neurological morbidity.
      Thus neurologists are increasingly faced with diagnosing or even predicting a
      wide spectrum of neurological complications of hepatitis C infection and/or its
      treatment.

PMID- 22991071
TI  - Hematological indices and activity of NTPDase and cholinesterase enzymes in rats
      exposed to cadmium and treated with N-acetylcysteine.
AB  - The present study aimed to investigate the influence of N-acetylcysteine (NAC) on
      cadmium (Cd) poisoning by evaluating Cd concentration in tissues, hematological
      indices as well as the activity of NTPDase, acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) enzymes of rats exposed to Cd and co-treated with
      NAC. For this purpose, the rats received Cd (2 mg/kg) and NAC (150 mg/kg) by
      gavage every other day for 30 days. Animals were divided into four groups (n = 6
      8): control/saline, NAC, Cd, and Cd/NAC. Cd exposure increased Cd concentration
      in plasma, spleen and thymus, and NAC co-treatment modulated this augment in both
      lymphoid organs. Cd exposure reduced red blood cell count, hemoglobin content and
      hematocrit value. Cd intoxication caused a decrease in total white blood cell
      count. NAC treatment per se caused an increase in lymphocyte and a decrease in
      neutrophil counts. On contrary, Cd exposure caused a decrease in lymphocyte and
      an increase in neutrophil and monocyte counts. NAC reversed or ameliorated the
      hematological impairments caused by Cd poisoning. There were no significant
      alterations in the NTPDase activity in lymphocytes of rats treated with Cd and/or
      NAC. Cd caused a decrease in the activities of lymphocyte AChE, whole blood AChE
      and serum BChE. However, NAC co-treatment was inefficient in counteracting the
      negative effect of Cd in the cholinesterase activities. The present investigation
      provides ex vivo evidence supporting the hypothesis that Cd induces
      immunotoxicity by interacting with the lymphoid organs, altering hematological
      parameters and inhibiting peripheral cholinesterase activity. Also, it highlights
      the possibility to use NAC as adjuvant against toxicological conditions.

PMID- 22991070
TI  - Update on progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a severe, often fatal,
      opportunistic viral infection of the central nervous system that is mainly seen
      in the context of AIDS and certain monoclonal immune-suppressive therapies. The
      causative agent, a polyoma virus, named JC virus infects only humans and there is
      no animal model for PML. This update focuses on information gathered in recent
      years on the pathogenesis of the disorder, on several clinical aspects associated
      with diagnosis and therapy, and on the immune reconstitution inflammatory
      syndrome (IRIS), a complication associated with removal of immunosuppressive
      therapy in PML.

PMID- 22991072
TI  - Annexin A1 mediates the anti-adhesive effects of the dexamethasone-treated
      promyelocytic leukemic cells.
AB  - Annexin A1 (AnxA1) is an important anti-inflammatory mediator during granulocytic
      differentiation in all trans-retinoic acid (ATRA) treated acute promyelocytic
      leukemic (APL) cells. Dexamethasone has been used successfully to prevent
      complications in ATRA-treated APL patients, although its mechanism of action is
      still not clear. In the present study, we have examined the effect of
      dexamethasone on the modulation of AnxA1 in ATRA-APL NB4 (ATRA-NB4) cells, ATRA
      NB4 cells-derived microparticles (MPs) and its role during cell-cell interaction
      between ATRA-NB4 cells and endothelial cells. Our results have shown that
      dexamethasone can inhibit the percentage of ATRA-NB4 cells expressing surface
      AnxA1 and its receptor FPR2/ALX in a time-dependent manner based on flow
      cytometric analysis. However, dexamethasone treatment of ATRA-NB4 cells has no
      significant effect on the level of AnxA1 mRNA, the total cellular level of AnxA1
      protein or the release of AnxA1 from these cells, as determined by RT-PCR,
      Western blotting, and ELISA, respectively. Further studies demonstrate that
      dexamethasone is able to significantly inhibit the adhesion of ATRA-NB4 cells to
      endothelial cells, and this anti-adhesive effect can be inhibited if the cells
      were pre-treated with a neutralizing antibody specific for AnxA1. Finally,
      dexamethasone also enhances the release of AnxA1-containing MPs from ATRA-NB4
      cells which can in turn prevent the adhesion of the ATRA-NB4 cells to endothelial
      cells. We conclude that biologically active AnxA1 originating from dexamethasone
      treated ATRA-APL cells and their MPs plays an anti-adhesive effect and this
      contributes to inhibit the adhesion of ATRA-APL cell to endothelial cells.

PMID- 22991073
TI  - Retraction of "The influence of mood on attribution," "Affects of the unexpected:
      When inconsistency feels good (or bad)," "Why people stereotype affects how they
      stereotype: The differential influence of comprehension goals and self
      enhancement goals on stereotyping," "Silence and table manners: When environments
      activate norms," and "Event accessibility and context effects in causal
      inference: Judgment of a different order".
AB  - The following five articles have been retracted from Personality and Social
      Psychology Bulletin by the Society for Personality and Social Psychology, and the
      Editor and the publisher of the journal: Avramova, Y.R., Stapel, D.A. & Lerouge,
      D. (2010). The influence of mood on attribution. Personality and Social
      Psychology Bulletin, 36, 1360-1371. (Original DOI: 10.1177/0146167210381083)
      Noordewier, M.K., & Stapel, D.A. (2010). Affects of the unexpected: When
      inconsistency feels good (or bad). Personality and Social Psychology Bulletin,
      36, 642-654. (Original DOI: 10.1177/0146167209357746 ) Van den Bos, A., & Stapel,
      D.A. (2009). Why people stereotype affects how they stereotype: The differential
      influence of comprehension goals and self-enhancement goals on stereotyping.
      Personality and Social Psychology Bulletin, 35(1), 101-113 (Original DOI:
      10.1177/0146167208325773) Joly, J.F., Stapel, D.A., & Lindenberg, S.M. (2008).
      Silence and table manners: When environments activate norms. Personality and
      Social Psychology Bulletin, 34(8), 1047-1056 (Original DOI:
      10.1177/0146167208318401) Stapel, D. A., & Spears, R. (1996). Event accessibility
      and context effects in causal inference: Judgment of a different order.
      Personality and Social Psychology Bulletin, 22, 979-992. (Original DOI:
      10.1177/01461672962210001).

PMID- 22991074
TI  - Catalyst-free synthesis of quinazolin-4-ones from (hetero)aryl-guanidines:
      application to the synthesis of pyrazolo[4,3-f]quinazolin-9-ones, a new family of
      DYRK1A inhibitors.
AB  - A small library of heterocycle-fused quinazolin-4-ones was prepared and evaluated
      as kinase inhibitors. The key step of the two-step process involves the
      environmental friendly thermolysis of N-ethoxycarbonyl-N'-(hetero) arylguanidines
      at 130  degrees C in water. The cyclization is fully regioselective. The most
      active molecules, 7-(2-hydroxyethylamino)- and 7-(3-hydroxypropylamino)
      pyrazolo[4,3-f]quinazolin-9-ones, inhibit DYRK1A and CLK1 at submicromolar
      concentrations, indicating the potential interest of this new heterocycle in drug
      design.

PMID- 22991075
TI  - Response to "Sodium current inhibition by nanosecond pulsed electric field
      (nsPEF)--fact or artifact?" by Verkerk et al.

PMID- 22991076
TI  - Utility of cVEMPs in bilateral superior canal dehiscence syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To determine the utility of cervical vestibular evoked
      myogenic potential (cVEMP) thresholds in the surgical management of bilateral
      superior canal dehiscence syndrome (SCDS). STUDY DESIGN: Retrospective review.
      METHODS: We identified patients who underwent surgical treatment for SCDS from
      our database of 147 patients diagnosed with superior canal dehiscence (SCD)
      between 2000 and 2011 at our institution. The diagnosis of SCDS was based on
      clinical signs and symptoms, audiometric and cVEMP testing, and high-resolution
      computed tomography. RESULTS: We identified 38 patients who underwent SCD surgery
      in 40 ears (2 bilateral). In seven patients with bilateral SCD, the more
      symptomatic ear had lower cVEMP thresholds, a larger air bone gap and a
      lateralizing tuning fork. In 13 patients with perioperative cVEMP testing,
      thresholds increased in 12 patients following primary repair, and no threshold
      shift was seen in one patient with persistence of symptoms after revision
      surgery. Audiometric data showed a significant mean decrease of the low-frequency
      air-bone gap and a mild (high-frequency) bone conduction loss after surgical
      repair. CONCLUSIONS: We found that, 1) preoperative cVEMP thresholds, the
      magnitude of the air-bone gap and tuning-fork testing are important to confirm
      the worse ear in patients with bilateral SCD, 2) elevation of cVEMP thresholds
      following surgery correlates with improvement of symptoms and underscores the
      importance of postoperative testing in patients with bilateral disease or
      recurrence of symptoms and, 3) SCD plugging is associated with a partial closure
      of the air-bone gap and a mild (high-frequency) sensorineural hearing loss.

PMID- 22991077
TI  - Toward mass producible ordered bulk heterojunction organic photovoltaic devices.
AB  - A strategy to fabricate nanostructured poly(3-hexylthiophene) (P3HT) films for
      organic photovoltaic (OPV) cells by a direct transfer method from a reusable soft
      replica mold is presented. The flexible polyfluoropolyether (PFPE) replica mold
      allows low-pressure and low- temperature process condition for the successful
      transfer of nanostructured P3HT films onto PEDOT/PSS-coated ITO substrates. To
      reduce the fabrication cost of masters in large area, we employed well-ordered
      anodic aluminum oxide (AAO) as a template. Also, we provide a method to fabricate
      reversed nanostructures by exploiting the self-replication of replica molds. The
      concept of the transfer method in low temperature with a flexible and reusable
      replica mold obtained from an AAO template will be a firm foundation for a low
      cost fabrication process of ordered OPVs.

PMID- 22991078
TI  - [Medical practice variation: supporting the null hypothesis in turbulent times].

PMID- 22991079
TI  - [Analysis of variables related with dementia mortality trend. Andalusia, Spain].
AB  - BACKGROUND: The dementias are a cause of mortality have increased over the last
      years. Therefore is important to analyze the variables more related to its
      development in Andalusia between 1999 and 2010. METHODS: With the deaths of 60
      and over by dementia from Andalusia Statistical Institute and the populations
      from corresponding years, are estimated crude mortality rates, standardized and
      age-specific; by joinpoint regression was calculated percentages annual change;
      and also, with the population estimates by marital status and deaths was
      calculated crude rates and standardized for age, sex and marital status. RESULTS:
      The standardized mortality rates increased from 124.8 to 161.0 deaths per 100,000
      in women and 110.3 to 147.7 in men, the annual increase was 4.2% and 3.8% in
      women and men. The women died more than men with a standardized rate ratio
      between 1.08 and 1.29. Age was the variable that determined mortality.
      CONCLUSIONS: Mortality from dementia in Andalusia has increased over the past 12
      years and will continue to increase with the consequent social and health impacts
      posed by these diseases, configured as a major health problem.

PMID- 22991080
TI  - [Review of mortality from hypertensive disease and diabetes mellitus after the
      error because of new death certificate: region of Murcia, Spain, 2009].
AB  - BACKGROUND: The Medical Death Certificate and the Death Statistics Bulletin were
      unified and implemented in the year 2009 in Spain. National statistics detected
      an unusual increase for diabetes mellitus (DM) and hypertensive disease (HT)
      deaths in 2009, in relation to previous years trend.The objective is to study the
      documental causes of the increase, and describe the procedures and consequences
      in rates, after the revision and recodification of DM and HT. METHODS: All death
      certificates in 2009 for diabetes and hypertension in the Region of Murcia
      (cases=670) were revised, according to previous guidelines for direct recoding
      after consultation to the certifying physician. A telephone survey to certifying
      physician was designed to determine the accuracy of the pattern of recoding.
      Kappa index and 95% confidence intervals (95%CI) were performed between initial
      and recoded causes. Confirmation rate and 95%CI was estimated after phone inquiry
      to the certifying physician, and the annual age-adjusted and age-specific rates
      from 1999 to 2009 (uncorrected and corrected) for DM and HT were calculated.
      RESULTS: Simple agreement was 37% for DM and 30% for HT. The Kappa index between
      the initial and final causes was 49% (95%CI, 45 to 54%). Confirmation rates were
      47% (95%CI, 43 to 52%) for DM and 38% (95%CI, 34 to 43%) for HT. The initial
      annual rates of 2009 for DM were corrected from 21.4 per 100,000 inhabitants to
      17.1, and from 19.0 to 14.0 for hypertension. The respective specific age rates
      of 70 to 84 and older experienced similar reductions. CONCLUSIONS: The revision
      restored temporal trends in mortality of DM and HT in 2009, and identified no
      variations from previous years. It was detected that the erroneous fulfillment of
      DM AND HT came from the new death certificate.

PMID- 22991081
TI  - [Variability in the reporting of adverse reactions to the pandemic and seasonal
      influenza vaccine: seasons 2009-2010 and 2010-2011. Valencian community, Spain].
AB  - BACKGROUND: The loss of confidence in the safety of vaccines derived from alarm
      conditions, as in the case of the flu pandemic may affect both vaccination
      coverage and the sensitivity to the reporting of suspected adverse reactions
      associated vaccines (SRAAV). The aim of the study is to describe the adverse
      effects reported to the vaccine against pandemic influenza in the 2009-2010
      season and against seasonal influenza in 2009-2010 and 2010-2011 seasons, by type
      of vaccine, risk groups and by age group in the Valencian Community (CV).
      METHODS: A retrospective descriptive study has been made of the individuals
      presenting suspected adverse reactions to the influenza vaccine reported through
      the Vaccine Information System during the seasons 2009-2010 and 2010-2011 in the
      Valencian Community. 95% confidence intervals were calculated. RESULTS: During
      the period 2009-2010 the reporting rate of suspected reactions for seasonal
      influenza vaccine was 0.020 per thousand doses administered, for the pandemic
      vaccine 0.95. The reporting rate for seasonal influenza vaccine in the period
      2010-2011 was 0.04 per thousand. CONCLUSIONS: There was an increase in the number
      of reported suspected adverse reactions to the pandemic vaccines compared with
      the rest of influenza vaccines, during the seasons. The highest suspected adverse
      reaction reporting rate was for the group of health professionals partner for
      both vaccines against seasonal and pandemic influenza.

PMID- 22991082
TI  - [Design and validation of scales to measure adolescent attitude toward eating and
      toward physical activity].
AB  - BACKGROUND: Different authors suggest that attitude is a mediator in behavior
      change, so it is a predictor of behavior practice. The main of this study was to
      design and to validate two scales for measure adolescent attitude toward healthy
      eating and adolescent attitude toward healthy physical activity. METHODS: Scales
      were design based on a literature review. After, they were validated using an on
      line Delphi Panel with eighteen experts, a pretest, and a pilot test with a
      sample of 188 high school students. Comprehensibility, content validity,
      adequacy, as well as the reliability (alpha of Cronbach test), and construct
      validity (exploratory factor analysis) of scales were tested. RESULTS: Scales
      validated by experts were considered appropriate in the pretest. In the pilot
      test, the ten-item Attitude to Eating Scale obtained alpha=0.72. The eight-item
      Attitude to Physical Activity Scale obtained alpha=0.86. They showed evidence of
      one-dimensional interpretation after factor analysis, a) all items got weights
      r>0.30 in first factor before rotations, b) the first factor explained a
      significant proportion of variance before rotations, and c) the total variance
      explained by the main factors extracted was greater than 50%. CONCLUSIONS: The
      Scales showed their reliability and validity. They could be employed to assess
      attitude to these priority intervention areas in Spanish adolescents, and to
      evaluate this intermediate result of health interventions and health programs.

PMID- 22991083
TI  - [Registry of preventive activities in women: variability in Vizcaya, Spain].
AB  - BACKGROUND: Several studies have reported that there is a lack of preventive
      activities performance in Primary Health Care, however in Vizcaya, the situation
      is not known, so, we decided determine the percentage of preventive activities
      carried out on women by primary care physicians which are recorded in the
      Electronic Health Record (Osabide), and analyze the characteristics which
      determine differences in registration between regions and physicians. METHODS: We
      conducted a cross-sectional study involving 425 women aged between 26 and 51
      years who were to the general practitioners' consult at least twice, and who were
      again on April 28, 29 or 30, 2011. We colleted as primary variable the registries
      of contraceptives practices (group aged between 26 and 51 years), the registries
      of cervical cytologies during the last five years, as well as the registries of
      mammograms performed during the two last years, and compared the medical record
      between men and women practitioners, health regions and between areas with and
      without centers for women, using the chi-square statistic. RESULTS: In 139
      (34.1%) of all women and in 99 (48.3%) of women aged between 26 and 51 years
      there was registry of cytologies and contraceptives practices respectively. The
      mammography performance was registered in 22 (10.7%) of women aged between 52 and
      65 years. CONCLUSIONS: The registry of preventive activities on women is low. We
      have observed differences by practitioners' gender.

PMID- 22991084
TI  - [User violence towards nursing staff in public hospitals: Murcia, Spain].
AB  - BACKGROUND: The workplace violence has special relevance for the health care
      workers. Nursing staff is one of the professions most affected by this risk. Our
      objective is to determine the prevalence during the past year of diverse hostile
      manifestations by users towards professional hospital nursing staff who depend on
      the "Servicio Murciano de Salud" [Health Service of Murcia] (SMS), as well as to
      detect the sociodemographic and occupational workers characteristics associated
      with higher exposure. METHODS: A cross-sectional study carried out during the
      year 2010 of a random sample of nursing personnel from all the hospitals of SMS,
      through a self-administered and anonymous survey (Ecoh-U scale). The sample was
      stratified by hospitals and services (30% of the workers) and finally we got a
      sample of 1.489 workers (confidence level 99%; sampling error 1,75%). We compared
      the punctuation average obtained in the scale according to variables
      sociodemographics and laborables. We used the test t of student in variables
      dichotomous and ANOVA and Tukey in variables multi-response. RESULTS: The 21,8%
      of the surveyed people reported that they suffered from "anger due to
      assistential delay" at least once a month. The workers who obtained punctuations
      significantly larger were psychiatric hospital workers (19,7), emergency workers
      (20,60), temporary (16,38) and with old 6-10 years in the profession (17,20).
      CONCLUSIONS: Although nursing staff is one of the professions most exposed to
      violence, the risk distribution is not homogeneous. Significant differences were
      found according to marital status, age, hospital, service, profession, contract
      type, shift and seniority in the profession.

PMID- 22991085
TI  - [Cancer Survival between 1995 and 2004 in the Basque Country, Spain].
AB  - BACKGROUND: geographic differences described in the prognosis of cancer patients
      in the Basque Country have been attributed to a different incidence in tumours
      with different lethality. Therefore, cancer relative survival adjusted by case
      mix was included to estimate cancer survival by provinces and health regions,
      using data from 1995 to 2004. METHODS: a total of 93 585 cases of malignant
      tumours were identified from a population-based cancer registry. The five-year
      relative survival (RS) was calculated using Ederer's method. The five-year
      relative excess risk (RER) of death was estimated with a generalised linear
      model, standardized by age and adjusted for sex, date of diagnosis and case-mix.
      RESULTS: the five-year RS increased from period 1995-1999 to 2000-2004, this
      latter, with values ranging by health regions between 46-58% and 57-65% in men
      and women, respectively. There was an excess risk of death in Bizkaia (RER=1.06,
      CI95%: 1.03-1.09), this same effect being identified in almost all the health
      regions in the province. In contrast, in Gipuzkoa province, differences were only
      statistically significant in the Gipuzkoa and Tolosa health regions (RER=1.07;
      CI95%: 1.02-1.13 and RER=0.91; CI95%: 0.84-0.98, respectively), and even these
      disappeared after adjusting for potential confounders. CONCLUSIONS: cancer
      patients of Bizkaia, except for the Uribe health region, presented a worse
      prognosis.

PMID- 22991086
TI  - [Agreement between Five Definitions of Metabolic Syndrome: Cartagena, Colombia].
AB  - BACKGROUND: During last decade the metabolic syndrome has been defined by five
      different guidelines. Discrepancies in such definitions could influence syndrome
      predictive ability over cardiovascular diseases. The aim of this study was to
      determine the degree of agreement between these five guidelines, in population
      from Cartagena (Colombia). METHODS: A cross sectional study was conducted in
      adults from urban zone. Sample size was estimated based on 2005 DANE census,
      which included 670 individuals. The prevalence of metabolic syndrome was
      determined through the WHO (World Health Organization), AHA/NHLBI (American Heart
      Association/National Heart Lung and Blood Institute), ATP III (Adult Treatment
      Panel III), IDF (International Diabetes Federation) and JIS (Joint Interim
      Statement) guidelines. Frequencies obtained were compared through Cohen's kappa
      index. RESULTS: According to JIS, IDF, ATPIII, AHA/NHBLI and WHO guidelines,
      metabolic syndrome prevalence was 36.3% [32.6 - 39.9], 35.1%, 30.3%, 24.2% and
      4.9%. Agreement between JIS and IDF was 0.893, while index for these two
      guidelines with AHA/NHLBI was 0.778 y 0.750, respectively. ATPIII had a lower
      agreement with JIS and IDF (0.711 and 0.645, respectively), however with
      AHA/NHLBI agreement was 0.863. WHO presented a agreement with the others
      guidelines between 0.14 and 0.16. CONCLUSIONS: Significant agreement was found
      between the four most recent guidelines. Abdominal obesity cut-off points might
      support differences agreement differences.

PMID- 22991087
TI  - High throughput sequencing approaches to mutation discovery in the mouse.
AB  - Phenotype-driven approaches in mice are powerful strategies for the discovery of
      genes and gene functions and for unravelling complex biological mechanisms.
      Traditional methods for mutation discovery are reliable and robust, but they can
      also be laborious and time consuming. Recently, high-throughput sequencing (HTS)
      technologies have revolutionised the process of forward genetics in mice by
      paving the way to rapid mutation discovery. However, successful application of
      HTS for mutation discovery relies heavily on the sequencing approach employed and
      strategies for data analysis. Here we review current HTS applications and
      resources for mutation discovery and provide an overview of the practical
      considerations for HTS implementation and data analysis.

PMID- 22991088
TI  - Accessing data from the International Mouse Phenotyping Consortium: state of the
      art and future plans.
AB  - The International Mouse Phenotyping Consortium (IMPC)
      (http://www.mousephenotype.org) will reveal the pleiotropic functions of every
      gene in the mouse genome and uncover the wider role of genetic loci within
      diverse biological systems. Comprehensive informatics solutions are vital to
      ensuring that this vast array of data is captured in a standardised manner and
      made accessible to the scientific community for interrogation and analysis. Here
      we review the existing EuroPhenome and WTSI phenotype informatics systems and the
      IKMC portal, and present plans for extending these systems and lessons learned to
      the development of a robust IMPC informatics infrastructure.

PMID- 22991090
TI  - Web-based clinical assessments for Parkinson's disease: reliable and feasible.

PMID- 22991089
TI  - Analysis of copy number variations in Holstein cows identify potential mechanisms
      contributing to differences in residual feed intake.
AB  - Genomic structural variation is an important and abundant source of genetic and
      phenotypic variation. In this study, we performed an initial analysis of copy
      number variations (CNVs) using BovineHD SNP genotyping data from 147 Holstein
      cows identified as having high or low feed efficiency as estimated by residual
      feed intake (RFI). We detected 443 candidate CNV regions (CNVRs) that represent
      18.4 Mb (0.6 %) of the genome. To investigate the functional impacts of CNVs, we
      created two groups of 30 individual animals with extremely low or high estimated
      breeding values (EBVs) for RFI, and referred to these groups as low intake (LI;
      more efficient) or high intake (HI; less efficient), respectively. We identified
      240 (~9.0 Mb) and 274 (~10.2 Mb) CNVRs from LI and HI groups, respectively.
      Approximately 30-40 % of the CNVRs were specific to the LI group or HI group of
      animals. The 240 LI CNVRs overlapped with 137 Ensembl genes. Network analyses
      indicated that the LI-specific genes were predominantly enriched for those
      functioning in the inflammatory response and immunity. By contrast, the 274 HI
      CNVRs contained 177 Ensembl genes. Network analyses indicated that the HI
      specific genes were particularly involved in the cell cycle, and organ and bone
      development. These results relate CNVs to two key variables, namely immune
      response and organ and bone development. The data indicate that greater feed
      efficiency relates more closely to immune response, whereas cattle with reduced
      feed efficiency may have a greater capacity for organ and bone development.

PMID- 22991091
TI  - Hyperbaric oxygen treatment prevents nitric oxide-induced apoptosis in articular
      cartilage injury via enhancement of the expression of heat shock protein 70.
AB  - Heat shock proteins (HSPs), inflammatory cytokines, nitric oxide (NO), and
      localized hypoxia-induced apoptosis are thought to be correlated to the degree of
      cartilage injury. We investigated the effect of hyperbaric oxygen (HBO) on (1)
      interleukin-1beta (IL-1beta)-induced NO production and apoptosis of rabbit
      chondrocytes and (2) healing of articular cartilage defects. For the in vitro
      study, RT-PCR and Western blotting were performed to detect mRNA and protein
      expressions of HSP70, inducible NO synthase (iNOS), and caspase 3 in IL-1beta
      treated chondrocytes. To clarify that the HSP70 was necessary for anti-iNOS and
      anti-apoptotic activity by HBO, we treated the cells with an HSP70 inhibitor,
      KNK437. For the in vivo study, cartilage defects were created in rabbits. The HBO
      group was exposed to 100% oxygen at 2.5 ATA for 1.5 h a day for 10 weeks. The
      control group was exposed to normal air. After sacrifice, specimen sections were
      sent for examination using a scoring system. Immunohistochemical analyses were
      performed to detect the expressions of iNOS, HSP70, and caspase 3. Our results
      suggested that HBO upregulated the mRNA and protein expressions of HSP70 and
      suppressed those of iNOS and caspase 3 in chondrocytes. KNK437 inhibited the HBO
      induced downregulation of iNOS and casapase 3 activities. The histological scores
      showed that HBO markedly enhanced cartilage repair. Immunohistostaining showed
      that HBO enhanced HSP70 expression and suppressed iNOS and caspase 3 expressions
      in chondrocytes. Accordingly, HBO treatment prevents NO-induced apoptosis in
      articular cartilage injury via enhancement of the expression of heat shock
      protein 70.

PMID- 22991092
TI  - Using dopamine research to generate rational cannabinoid drug policy.
AB  - The recent rise in the recreational use of synthetic cannabinoids (e.g. 'K2' and
      'Spice') has been accompanied by a corresponding increase in regulation. Besides
      prohibition of specific compounds and general class bans in over forty states,
      five synthetic cannabinoids (CB) are federally regulated under a 'temporary' ban
      and are currently under a formal review to determine whether to permanently
      schedule them. Whether through explicit prohibition of specific chemicals, or
      potential de facto bans of unofficially scheduled compounds through the analogue
      act, scheduling CBs may significantly impede researching their therapeutic
      utility and elucidating physiological roles of the endogenous CB system. We argue
      that a review of neuroscience research suggests that synthetic CBs that act like
      Delta9-tetrahydrocannabinol (THC) by directly binding to and stimulating CB
      receptors (i.e. direct agonists), as well as novel drugs that indirectly
      stimulate these receptors by increasing levels of endogenous CB neurotransmitters
      (i.e. indirect agonists) have therapeutic value. Specifically, neurochemical
      research into how CBs influence mesolimbic dopamine release, a reliable and
      consistent marker of drugs' rewarding/reinforcing effects, provides the most
      useful indication of CB abuse liability, and may have implications for the
      generation of rational drug policy. It demonstrates that direct CB receptor
      agonists, but not indirect agonists, increase mesolimbic dopamine release. Thus,
      while direct CB receptor agonists pose an abuse liability, indirect agonists do
      not. We recommend regulatory agencies revise policies that treat these separate
      CB classes similarly and to curb regulation aimed at any CB receptor agonists as
      Schedule I, as this ignores their medicinal properties.

PMID- 22991093
TI  - Activin A is essential for Feeder-free culture of human induced pluripotent stem
      cells.
AB  - Feeder-free culture of human induced pluripotent stem (hiPS) cells is necessary
      for their clinical application to avoid adverse effects of foreign proteins. hiPS
      cells were cultured with combinations of activin (A), CHIR99021 (C), basic
      fibroblast growth factor (F), and leukemia inhibitory factor (L) under feeder
      free conditions. Culture was terminated after 12 passages or when the cell
      morphology changed from pluripotency. Pluripotency was analyzed by alkaline
      phosphatase (ALP) staining and immunostaining with antibodies to Oct3/4, Nanog,
      SSEA4, and TRA-1-60. SB431542 (SB), an activin inhibitor, was added to the
      culture, and the morphology of the cells was observed. hiPS cells cultured with
      A, AC, and ACL after 12 passages were positive for ALP staining. Oct3/4 was
      positive in hiPS cells cultured with A, AC, and ACL. hiPS cells were positive for
      Nanog when cultured with A and AC; however, Nanog signal was weaker in cells
      cultured with ACL. SSEA4 was positive in hiPS cells cultured with A and AC but
      almost negative in those cultured with ACL. hiPS cells were positive for TRA-1-60
      when cultured with A, AC, and ACL. hiPS cells lose their undifferentiated
      morphology at six passages when cultured with A + SB, five passages with AC + SB,
      and nine passages with ACL. We conclude that feeder-free culture of hiPS cells
      requires A or AC to maintain pluripotency.

PMID- 22991094
TI  - Comparative evaluation of Borelli's lactritmel agar and Lowenstein-Jensen agar
      for conidiation in the Trichophyton mentagrophytes and Trichophyton rubrum
      complexes.
AB  - The characteristics of macroconidia are the key to the identification of
      dermatophytic fungi. In this study, we compared Lowenstein-Jensen agar (LJA) with
      Borelli's lactritmel agar (BLA) for the ability to induce macroconidia production
      in a collection of Trichophyton mentagrophytes (12) and Trichophyton rubrum (12)
      complexes and in Arthroderma isolates (4). We evaluated 28 strains from across
      the world, which were mainly obtained from the culture collection of the
      Centraalbureau voor Schimmelcultures, Fungal Biodiversity Centre, The
      Netherlands. All cultures were incubated at 26  degrees C on the bench, and
      conidia formation was investigated every 5 days, over a period of 30 days after
      inoculation. At 15 days, strains grown on BLA demonstrated better macroconidia
      production than those grown on LJA, 23 (82.1%) versus 16 (57.1%) isolates,
      respectively. Thus, the use of BLA, an inexpensive medium that can be prepared in
      the laboratory, should facilitate conidiation and the presumptive identification
      of dermatophytic fungi in mycology and clinical microbiology laboratories.

PMID- 22991095
TI  - Antifungal activity of sodium bicarbonate against fungal agents causing
      superficial infections.
AB  - Although sodium bicarbonate-NaHCO(3) (SB) has many domestic and medical,
      traditional and empirical uses, only little scientific documentation of its
      activity is available. The aims of this study were to investigate the antifungal
      activity of SB on the three fungal groups (yeasts, dermatophytes and molds)
      responsible for human skin and nail infections. We first evaluated the in vitro
      antifungal activity of SB on 70 fungal strains isolated from skin and nail
      infections: 40 dermatophytes, 18 yeasts and 12 molds. A concentration of 10 g/L
      SB inhibited the growth of 80% of all the fungal isolates tested on Sabouraud
      dextrose agar. The minimal inhibitory concentration 90 (MIC90) of SB measured on
      Sabouraud dextrose agar, Sabouraud dextrose broth and potato dextrose broth was 5
      g/L for the yeasts, 20 g/L for the dermatophytes and 40 g/L for the molds. In a
      second step, we prospectively evaluated the ex vivo antifungal activity of SB on
      24 infected (15 dermatophytes, 7 yeasts and 2 molds) clinical specimens (15 nails
      and 9 skin scrapings). The fungal growth was completely inhibited for 19 (79%)
      specimens and reduced for 4 (17%) specimens after 7 days of incubation on
      Sabouraud dextrose-chloramphenicol agar supplemented with 10 g/L of SB as
      compared to Sabouraud dextrose-chloramphenicol agar without SB. In conclusion, we
      documented the antifungal activity of SB on the most common agents of cutaneous
      fungal infection and onychomycosis, and we specified the effective concentrations
      for the different groups of pathogenic fungi. The mechanism of action of SB has
      yet to be explored.

PMID- 22991096
TI  - Activation of carboplatin by carbonate: a theoretical investigation.
AB  - We carried out a theoretical study to investigate the thermodynamics and the
      kinetics of the activation of the anticancer drug carboplatin in a carbonate
      buffer, a process which has been suggested to play an important role in the
      uptake, antitumor activity and toxicity of this drug. The initial stages of this
      process have been investigated by considering both the carbonate and the
      bicarbonate ions, the main species in a carbonate buffer at physiological pH, as
      the attacking species and consist of an initial ring-opening step, involving the
      displacement of one arm of the chelating ring by the carbonate ion, followed by
      the protonation of the ring-opened carbonate to the corresponding bicarbonate
      species and its subsequent decarboxylation to give the final hydroxo product. The
      obtained results show that the overall process is exoergonic with relatively low
      activation free energy (below 120 kJ mol(-1)), suggesting that the reaction with
      carbonate might represent a viable pathway for the activation of carboplatin to
      give active intermediates which, in the biological environment, may easily
      further react to give thermodynamically more stable species.

PMID- 22991097
TI  - Association of pulmonary artery obstruction index with elevated heart-type fatty
      acid binding protein and short-term mortality in patients with pulmonary embolism
      at intermediate risk.
AB  - PURPOSE: Heart-type fatty acid binding protein (H-FABP) is a sensitive marker of
      myocardial injury and predictor of worse prognosis in patients with pulmonary
      embolism (PE). Assessment of right ventricular dysfunction and pulmonary artery
      obstruction index (PAOI) with computed tomography (CT) has been reported as a
      predictor of mortality in PE. Therefore, we aimed to assess the correlation
      between H-FABP and CT angiographic PAOI in PE patients at intermediate risk.
      MATERIALS AND METHODS: Sixty-one patients (28 males; mean age, 62 +/- 17 years)
      with diagnosis of PE were included in this study. CT was performed in all
      patients, and the following parameters were evaluated: right ventricle/left
      ventricle ratio (RV/LV), pulmonary artery axial diameter, superior vena cava
      axial diameter, and PAOI determined with Qanadli score. Blood samples were
      assessed for H-FABP and troponin levels. Patients were followed for 30 days after
      discharge. RESULTS: Mean PAOI was 57 +/- 18%. Eleven patients died during the
      follow-up period due to PE (18% mortality rate). H-FABP was positive in 21
      patients (35%). There was no difference in CT parameters between patients with
      positive H-FABP and negative H-FABP. In addition, CT parameters were similar
      between patients who survived and those who did not. RV/LV ratio correlated with
      PAOI score. Among the biomarkers, troponin levels correlated with both RV/LV
      ratio and PAOI. H-FABP was an independent predictor of mortality. PAOI and RV/LV
      ratio did not predict 30-day mortality. CONCLUSION: Although H-FABP positivity
      confers a bad prognosis on PE patients at intermediate risk, PAOI did not predict
      mortality in this group.

PMID- 22991098
TI  - High prevalence of complementary and alternative medicine use in the Dutch
      pediatric oncology population: a multicenter survey.
AB  - Although complementary and alternative medicine (CAM) is widely used in the
      pediatric population, research on the use of these therapies in the pediatric
      oncology population is of mixed quality. In this multicenter survey, we
      investigated the prevalence of CAM use, possible determinants of use, and
      parental attitude towards communication and research on CAM therapies. The
      prevalence of CAM use in the past 12 months was assessed by using a questionnaire
      based on the European guidelines on CAM research, filled out by parents of
      children visiting pediatric oncology outpatient clinics of six academic hospitals
      in the Netherlands. The questionnaire consisted of 26 questions on the child's
      clinical status, CAM use, and attitude towards communication and research on CAM
      therapies. One hundred and twenty-two of 288 respondents (42.4 %) reported CAM
      use. The most frequently used categories were homeopathy (18.8 %) and dietary
      supplements (11.5 %). Female gender and parental CAM use were significant
      predictors for the use of CAM (p < 0.001). Only one third of the parents had
      discussed CAM use with their pediatric oncologist. More than 80 % of the
      respondents identified a need for information about CAM from their pediatrician
      and 85.7 % was positive towards research on CAM. Half of the parents were
      interested in participating in future CAM trials. Conclusion, with more than 40 %
      of parents of Dutch pediatric oncology patients providing complementary and
      alternative medicine to their child and with lacking evidence on efficacy and
      safety of most CAM modalities, there is a clear need for high-quality research in
      this field. This study shows that most parents have an open attitude towards CAM
      research and that almost half of the parents would consider participating in
      future CAM trials, paving the way for research on CAM and aiming for its evidence
      based use in pediatric oncology.

PMID- 22991099
TI  - High-content single-cell analysis on-chip using a laser microarray scanner.
AB  - High-content cellomic analysis is a powerful tool for rapid screening of cellular
      responses to extracellular cues and examination of intracellular signal
      transduction pathways at the single-cell level. In conjunction with microfluidics
      technology that provides unique advantages in sample processing and precise
      control of fluid delivery, it holds great potential to transform lab-on-a-chip
      systems for high-throughput cellular analysis. However, high-content imaging
      instruments are expensive, sophisticated, and not readily accessible. Herein, we
      report on a laser scanning cytometry approach that exploits a bench-top
      microarray scanner as an end-point reader to perform rapid and automated
      fluorescence imaging of cells cultured on a chip. Using high-content imaging
      analysis algorithms, we demonstrated multiplexed measurements of morphometric and
      proteomic parameters from all single cells. Our approach shows the improvement of
      both sensitivity and dynamic range by two orders of magnitude as compared to
      conventional epifluorescence microscopy. We applied this technology to high
      throughput analysis of mesenchymal stem cells on an extracellular matrix protein
      array and characterization of heterotypic cell populations. This work
      demonstrates the feasibility of a laser microarray scanner for high-content
      cellomic analysis and opens up new opportunities to conduct informative cellular
      analysis and cell-based screening in the lab-on-a-chip systems.

PMID- 22991100
TI  - What the DSM-5 portends for research, diagnosis, and treatment of autism spectrum
      disorders.
AB  - In May 2013 the APA will release DSM-5, which will restructure the diagnostic
      classification for autism spectrum disorders (ASDs) into a single category. The
      proposed changes in DSM-5 aim to better reflect the current state of research by
      consistently identifying the core features in social/communication and
      restrictive and repetitive behaviors that are specific to ASDs. This review
      describes the empirical and theoretical bases of research in the nosology of
      ASDs, given the impending shift in DSM-5 diagnostic criteria. General issues in
      diagnosis and prevalence are described, with differences between DSM-IV and DSM-5
      highlighted. To address concerns about the application of the proposed DSM-5
      criteria, the current literature assessing the sensitivity and specificity of the
      proposed DSM-5 criteria is reviewed. Last, we discuss the implications of the
      changes in DSM-5 for the treatment of ASDs and recommend areas for future
      research.

PMID- 22991101
TI  - Sparing the larynx and esophageal inlet expedites feeding tube removal in
      patients with stage III-IV oropharyngeal squamous cell carcinoma treated with
      intensity-modulated radiotherapy.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the effect of larynx and esophageal inlet
      sparing on dysphagia recovery after intensity-modulated radiotherapy (IMRT) for
      stage III-IV oropharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective
      study. METHODS: Of 88 patients treated with IMRT, 38 were planned with a larynx +
      esophageal inlet mean dose <50 Gy constraint, 27 with a larynx alone mean dose
      constraint of <50 Gy, and 23 without a larynx/esophagus constraint. All had a
      percutaneous endoscopic gastrostomy (PEG) tube placed before IMRT, which was
      removed when the patient could swallow and maintain weight. All IMRT plans were
      retrieved, and the larynx; esophageal inlet; and superior, middle, and inferior
      constrictors were contoured. Dosimetric data were correlated with PEG tube
      dependence duration. RESULTS: The PEG tube was removed within 3, 6, 9, and 12
      months after IMRT in 24%, 61%, 71%, and 83% of patients, respectively. Median
      times to PEG tube removal were 3.7 and 8.6 months (P = .0029) in patients planned
      with or without a larynx/larynx + esophageal inlet dose constraint. A mean dose
      to the larynx + esophageal inlet of <=60 Gy reduced the median PEG tube duration
      from 10.8 to 6.1 months (P = .02), compared to >60 Gy. Mean pharyngeal
      constrictor doses in patients receiving a mean dose to the larynx + esophageal
      inlet of <=50 Gy versus >50 Gy were: 60 Gy and 69 Gy, 55 Gy and 67 Gy, and 47 Gy
      and 57 Gy, for the superior, middle, and inferior constrictors, respectively (P <
      .0001). CONCLUSIONS: A dose constraint on the larynx and esophageal inlet during
      IMRT planning reduces dose to pharyngeal constrictors and expedites PEG tube
      removal.

PMID- 22991102
TI  - Rights of the child and adolescent: current challenges.

PMID- 22991103
TI  - Patient safety in care circumstances: prevention of adverse events in the
      hospitalization of children.
AB  - This case study with a qualitative approach presents an analysis of the
      perceptions of family caregivers/companions and health workers concerning adverse
      events in care contexts. A total of 15 companions and 23 health workers from
      pediatric hospitalization units of a university hospital in Porto Alegre, Brazil
      participated in this study from August to December 2010. Data were collected
      through semi-structured interviews and analyzed through thematic content analysis
      using QSR's Nvivo version 7.0. Seven thematic categories emerged from the
      analysis. The results highlight reviewing and checking workers' interventions and
      implementing effective communication among workers, caregivers and children. The
      main recommendations concern changing the organizational culture of health
      facilities, emphasizing safe care and a systemic view of the evaluation of
      adverse events.

PMID- 22991104
TI  - Maternal factors regulating preterm infants' responses to pain and stress while
      in maternal kangaroo care.
AB  - The relationship between maternal factors and the response of preterm infants to
      pain and stress experienced during heel puncture while in maternal kangaroo care
      was investigated. This descriptive study included 42 mothers and their preterm
      infants cared for in a neonatal unit. Data were collected in the baseline,
      procedure, and recovery phases. We measured the neonates' facial actions, sleep
      and wake states, crying, salivary cortisol levels, and heart rate, in addition to
      the mothers' behavior, salivary cortisol levels, and mental condition. The
      influence of the maternal explanatory variables on the neonatal response
      variables were verified through bivariate analysis, ANOVA, and multiple
      regression. The mothers' behavior and depression and/or anxiety did not affect
      the neonates' responses to pain and stress, though the mothers' levels of
      salivary cortisol before the procedure explained the variance in the neonates'
      levels of salivary cortisol after the procedure (p=0.036). Additionally, the
      mothers' baseline levels of salivary cortisol along with the neonates' age
      explained the variance in the neonates' heart rate (p=0.001). The ability of
      mothers to regulate their own stress contributed to the infants' responses to
      pain and stress.

PMID- 22991105
TI  - Judiciary as the last resort to protect children and adolescents: intersectoral
      actions, investment in human resources, and structuring of services.
AB  - This study aimed to identify the work developed by the Judiciary to prevent
      sexual violence against children and adolescents within the family. The approach
      to social representations in a cultural perspective was used. The field study
      consisted in the 1st and 2nd Court of Crimes against Children and Adolescents, at
      the State Supreme Court of Pernambuco, Brazil. Participant observation, semi
      structured interviews, and focus group with 17 subjects were the techniques for
      data collection, analyzed through the interpretation of meanings, allowing the
      identification of the category "The Judiciary as the ultimate level" and the
      following subcategories: "The public policies to prevent violence" and "The
      structure and dynamics of Courts". This study allows the visualization of the
      Judiciary's limitations with regard to the full protection and absolute priority,
      and that the work along with the victims demands investments in structure and
      human resources.

PMID- 22991106
TI  - The therapeutic journey of families of children with respiratory diseases in the
      public health service.
AB  - This study's purpose was to identify the therapeutic journey of families seeking
      health care for their children with respiratory diseases. This qualitative study
      had the participation of parents of children younger than five years old who were
      hospitalized with respiratory diseases. Path mapping was used as an instrument to
      collect data, which was analyzed through thematic analysis. The findings indicate
      that families sought the health services as soon as they perceived symptoms and
      had access to medical care, however such care was not decisive in resolving their
      health issues. Even though the families returned to the service at least another
      three times, the children had to be hospitalized. The attributes of primary
      health care were not observed in the public health services, while therapeutic
      encounters had no practical success.

PMID- 22991107
TI  - Nutritional status and weight gain in pregnant women.
AB  - This study described the nutritional status of 228 pregnant women and the
      influence of this on birth weight. This is a retrospective study, developed in a
      health center in the municipality of Sao Paulo, with data obtained from medical
      records. Linear regression analysis was carried out. An association was verified
      between the initial and final nutritional status (p<0.001). The mean of total
      weight gain in the pregnant women who began the pregnancy underweight was higher
      compared those who started overweight/obese (p=0.005). Weight gain was
      insufficient for 43.4% of the pregnant women with adequate initial weight and for
      36.4% of all the pregnant women studied. However, 37.1% of those who began the
      pregnancy overweight/obese finished with excessive weight gain, a condition that
      ultimately affected almost a quarter of the pregnant women. Anemia and low birth
      weight were uncommon, however, in the linear regression analysis, birth weight
      was associated with weight gain (p<0.05). The study highlights the importance of
      nutritional care before and during pregnancy to promote maternal-infant health.

PMID- 22991108
TI  - The perspectives of Brazilian homemakers concerning living with type 2 diabetes
      mellitus.
AB  - The purpose of this study is to present an understanding of the experience of
      Brazilian homemakers with type 2 diabetes mellitus (DM2). A descriptive
      exploratory design was used and semi-structured interviews were conducted with 25
      Brazilian homemakers concerning their experience. The interviews were recorded,
      transcribed, and the resulting text was analyzed using the sequential step
      method. Data converged to one dominant category, "constructing one's identity in
      the family context", which is comprised of three categories: gender differences;
      day-to-day concerns; and incongruity between knowledge and behavior related to
      DM2. These findings suggest that participants construct their identities within
      the family context and that their experience of living with DM2 is integral to
      their self-identification as wives and mothers. This, in turn, has implications
      for the design and implementation of programs to assist women in managing DM2
      effectively.

PMID- 22991109
TI  - The effect of educational intervention on the disease knowledge of diabetes
      mellitus patients.
AB  - The prevention of diabetes and its complications is a challenge for the
      healthcare team. The aim of this study was to evaluate the effect of educational
      action on the disease knowledge of patients with type 2 diabetes. A randomized
      clinical trial was conducted with 62 patients registered in a service of
      reference in the treatment of hypertension in 2010. Data were collected through a
      questionnaire applied to the Intervention (IG) and Control (CG) groups at the
      beginning and at the end of the study. The IG participated in group educational
      activities, using problematization methodology. The results showed a significant
      increase in knowledge about diabetes in the patients of the IG, in all the topics
      (p<0.05). In the CG, some changes were observed in knowledge, however, these were
      fewer when compared with the IG. In conclusion, it was possible to increase
      disease knowledge through the performance of educational activities. Clinical
      trial identifier: RBR-58n26h.

PMID- 22991110
TI  - Analysis of action plans and coping plans for reducing salt consumption among
      women with hypertension.
AB  - This cross-sectional study, based in implementation intention theory, describes
      action plans developed by women with hypertension (n=49) to add no more than 4g
      of salt per day to food and to reduce consumption of salty foods, as well as
      describing the barriers perceived and the coping strategies adopted for putting
      the action plans into practice. The plans were categorized according to
      similarities and were submitted to frequency analysis. The majority of the action
      and coping plans had to do with the effectuation of the behavior involving adding
      up to 4g of salt per day per person to food. The action strategies were aimed at
      quantifying the salt added, and the main obstacles were related to the reduced
      palatability of the food made with less salt. The coping plans have to do with
      preparing foods separately and to using natural seasonings instead of salt. This
      data can help the nurse to design activities for clinical education, with a view
      to reducing salt consumption among patients who prepare their own food.

PMID- 22991111
TI  - Fatigue in colorectal cancer patients: prevalence and associated factors.
AB  - This study identified the prevalence and predictors of fatigue in colorectal
      cancer (CRC) patients. Cross-sectional study with 157 adult CRC outpatients (age
      60+/-11.7 years; 54% male; cancer stage IV 44.8%). The Piper Fatigue Scale
      revised was used to assess fatigue scores. Socio-demographic, clinical,
      depression, performance status, pain and sleep disturbance data were assessed.
      Associations between fatigue and these data were analyzed through logistic
      regression models. Fatigue was reported by 26.8% patients. Logistic regression
      identified three predictors: depression (OR: 4.2; 95%CI 1.68-10.39), performance
      status (OR: 3.2; 95%CI 1.37-7.51) and sleep disturbance (OR: 3.2; 95%CI 1.30
      8.09). When all predictors were present, the probability of fatigue occurrence
      was 80%; when none were present, the probability was 8%. The model's specificity
      and sensitivity were 81.9% and 58.6%, respectively. Through the assessment of
      depression, performance status and sleep disturbance, the probability of fatigue
      occurrence can be estimated, and preventive and treatment strategies can be
      rapidly implemented in clinical practice.

PMID- 22991112
TI  - Validation of defining characteristics for the nursing diagnosis of fatigue in
      oncological patients.
AB  - The objective of this study was to validate the defining characteristics for the
      nursing diagnosis of Fatigue in adult oncological patients. It is a cross
      sectional, descriptive study with a quantitative perspective, and its type is
      diagnostic content validation. Data collection was carried out in a University
      Hospital. The sample was made up of 35 expert nurses. The instrument used was
      subdivided into four parts. The data was analyzed by descriptive statistics. 15
      defining characteristics were identified, considered secondary indicators. With
      an average weighting of less than 0.50, four defining characteristics were
      excluded. The defining characteristic Impaired social interaction, added to those
      described by NANDA-I after review of the literature, was validated with a
      weighted average of 0.71. It was concluded that the subjectivity of the defining
      characteristics and the difficulty nurses have in recognizing them influence the
      identification of this diagnosis.

PMID- 22991113
TI  - Massage application for occupational low back pain in nursing staff.
AB  - This is a clinical trial which aims to evaluate the efficiency of massage in the
      reduction of occupational low back pain, and its influence on the performance of
      work and life activities for the nursing team. The sample consisted of 18
      employees who received seven to eight sessions after their work period. From the
      Numerical Pain Rating Scale, significant improvements were found between the 3rd
      and 1st evaluations (p=0.000) and between the 3rd and 2nd (p=0.004), using the
      Wilcoxon test. Regarding the Oswestry Disability Index, the paired t test showed
      a statistical difference (p=0.02) between the baseline, with a mean of 21.33% and
      the second evaluation (18.78%), which was also seen between the second and third
      evaluation (16.67%). The score for the Handling and Transfer Risk Evaluation
      Scale was 18 points (medium risk). It is concluded that massage was effective in
      reducing occupational low back pain, and provided improvement in activities of
      work and life. Clinical Trials Identifier: NCT01315197.

PMID- 22991114
TI  - Work capacity, sociodemographic and work characteristics of nurses at a
      university hospital.
AB  - This cross-sectional study evaluated the work capacity of 195 nurses at a
      university hospital, from a calculation of sample size with a Confidence Interval
      (CI) of 95%. The data was collected by means of the Work Capacity Index (WCI)
      instrument and analyzed by statistical analysis. 94.5% of the sample was made up
      of women; the average age was of 42.6 years (sd=8.5); 66.5% had partners and
      76.7% were educated to post-graduate level. 36.0% worked the night shift; 28.4%
      the morning shift and 20.8% the afternoon shift. The average score given to work
      capacity was Good (41.8 points) and there was a significant correlation with pay
      (p-value<0.05), satisfaction with workplace (p-value=0.001) and feeling valued by
      the institution (p-value=0.003). The group which carried out family activities
      showed higher scores in the WCI compared to those who did not (p-value=0.009).
      The nurses presented differing sociodemographic and work aspects, with a high
      capacity for work.

PMID- 22991115
TI  - Prevalence of alcohol, tobacco and street drugs consumption in adult Latin
      American immigrants.
AB  - To estimate the prevalence of alcohol, tobacco and illicit drug consumption
      (through the self-report) in adult Latin-American immigrants of Seville, a cross
      sectional descriptive study was carried out in a representative sample of 190
      immigrants. The results showed that 61.4% of the participants had consumed
      alcohol in previous month before data collection, although 13.2% of them were at
      risk of alcoholism. Moreover, 30.0% were smokers. In addition, 5.3% of the
      interviewed people had consumed illicit psychoactive substances in the previous
      six months (Marihuana: 3.7%, hashish: 1.1% and cocaine: 0.5%). For all substances
      under analysis, the consumption prevalence was much higher in men from 25 to 39
      years of age. In conclusion, prevalence levels of this consumption were high
      among the studied immigrants. Nurses could train the population in the prevention
      of these risk behaviors through preventive practices.

PMID- 22991116
TI  - Risk behavior for the human immunodeficiency virus among motel clients.
AB  - This study aimed to verify risk behavior for infection with the Human
      Immunodeficiency Virus in people who attended motels. This is a cross-sectional
      study conducted in two motels in two municipalities in the state of Minas Gerais,
      Brazil, with a sample of 308 randomly selected individuals, aged between 18 and
      60 years. Bivariate (chi-square and t test for independent samples) and
      multivariate (logistic regression) statistical tests were performed. A total of
      45.8% of the participants reported not having used a condom during the last
      vaginal sexual intercourse, 48.4% did not use a condom during the last oral sex,
      while 26.3% reported not having used a condom in the last anal intercourse.
      Having a steady partner was the strongest predictor of not using condoms.
      Probable beliefs regarding loyalty involved in a stable relationship may be
      contributing to the failure to use condoms during intercourse, increasing the
      risk of HIV infection.

PMID- 22991117
TI  - Incidence of gastric extubation of users in a home care program of a university
      hospital.
AB  - This quantitative, prospective study, aimed to characterize the profile of users
      and caregivers and to measure the incidence of gastric extubation, identifying
      the type and the reasons for the extubation of these users in a Home Care Program
      of a university hospital. The population consisted of 37 subjects and the data
      were collected from April to August 2010. For the analysis, descriptive
      statistics, test of significance of 5% and calculation of indicators were
      adopted. It was found that 51.4% of the users were female, 67.5% in the age group
      >60 years and 67.6% presented neurological diseases. Regarding the caregivers
      89.2% were female and their mean age was 50.6 years. The incidence of extubation,
      considering 100 days of intubation, corresponded to 1.08, with 0.26 planned and
      0.82 unplanned (p=0.009). These results allowed the rates to be calculated of the
      extubation of patients with gastric intubation for nutritional support in
      domicile care, providing support in establishing care and management goals for
      the continuous improvement of quality.

PMID- 22991118
TI  - Learning strategies used by undergraduate and postgraduate students in hybrid
      courses in the area of health.
AB  - This study aimed to investigate the learning habits and strategies of
      undergraduate and post-graduate students matriculated in hybrid courses in the
      area of healthcare at a Brazilian university. 220 graduate students were invited
      to participate in the research, of whom 67.27% accepted. An exploratory
      methodology was utilized, which analyzed quantitative data collected by a
      structured instrument. A similarity may be observed between undergraduate and
      postgraduate students concerning the majority of education habits and learning
      strategies, such as the large proportion of those who read more than half of the
      course content and of those who preferred to study alone, as well as in the high
      use of the majority of strategies evaluated. It is concluded that both the groups
      present appropriate study habits and satisfactorily used the learning strategies
      investigated.

PMID- 22991119
TI  - Reliability and validity of spirituality questionnaire by Parsian and Dunning in
      the Spanish version.
AB  - The aim of this methodological study was to translate, culturally adapt and
      assess the internal consistency and validity of the Spanish version of the
      "Spirituality Questionnaire". The sample comprised 204 young people between 18
      and 25 years of age from two universities in Bogota. Cronbach's Alpha was used
      for reliability, while groups of experts and young people were used for construct
      validity. Exploratory and confirmatory factor analysis was used for construct
      validity. The reliability score of the total instrument was 0.88. The overall
      index of content validity corresponded to 0.90. Exploratory factor analysis
      showed that four factors explain 52.60% of the variance. The originally proposed
      theoretical model was confirmed and, in two dimensions, a different structure was
      proposed. In conclusion, the instrument "Spirituality Questionnaire" by Parsian
      and Dunning is reliable and valid in the Spanish version.

PMID- 22991120
TI  - Study of the measurement properties of the Portuguese version of the Well-Being
      Questionnaire12 (W-BQ12) in women with pregnancy loss.
AB  - The assessment of well-being can be an important parameter in monitoring the
      process of mourning. In this study we sought to assess the applicability of the W
      BQ12 - Well-Being Questionnaire - in a sample consisting of 74 women between four
      and six weeks following their respective pregnancy losses, analyzing its
      measurement capabilities. As proposed by the author, the analysis of the scale's
      primary components and the discriminating convergent validity confirmed the
      dimensional structure of three subscales. The scale showed good reliability
      (global Cronbach's Alpha coefficient = 0.84), and, overall, the items showed a
      good correlation with the corresponding subscale. Generally speaking, the W-BQ12
      showed good discriminative validity when correlated with the PBGS - Perinatal
      Bereavement Grief Scale. This tool, applied to this study, was found to be both
      reliable and valid for use by nurses in assessing the well-being of women who
      have experienced this type of loss.

PMID- 22991121
TI  - Cross-cultural adaptation of the Safety Attitudes Questionnaire - Short Form 2006
      for Brazil.
AB  - The objective of this study was to perform a cross-cultural adaptation of the
      Safety Attitudes Questionnaire - Short Form 2006 for Brazil. The instrument was
      applied in six hospitals in three regions of Brazil. Content, face, and construct
      validity was performed. Analysis of the instrument's reliability was performed by
      verifying the items' internal consistency through Cronbach's alpha. The sample
      was composed of 1301 professionals working in clinical and surgical wards of six
      hospitals. Confirmatory analysis showed that the model including 41 items was
      satisfactory. The Portuguese version presented an alpha of 0.89. The item-total
      correlations among the domains were moderate to strong, except for the domain
      Stress Recognition. We concluded that the instrument's version adapted to
      Portuguese and applied in our sample is valid and reliable.

PMID- 22991122
TI  - The Bristol Stool Form Scale: its translation to Portuguese, cultural adaptation
      and validation.
AB  - The Bristol Stool Form Scale is used for describing feces. The objective of this
      research was its translation, cultural adaptation and validation for Brazil. The
      methodology was translation, back-translation and discussion. Validation involved
      85 nurses, 80 doctors, and 80 patients, who correlated images of seven types of
      feces with the descriptions. RESULTS: there was a difference in sex distribution,
      with males predominating among the doctors and females among nurses and patients.
      In relation to concordance between definitions and pictures, the highest
      percentage was in type 5 in all three groups and the lowest was in types 6 and 7
      for the doctors, in type 3 for the nurses, and type 6 for the patients. The
      general Kappa index was 0.826. CONCLUSION: the scale demonstrated high
      reliability for all the groups studied.

PMID- 22991123
TI  - Confirmatory factor analysis of the Portuguese Depression Anxiety Stress Scales
      21.
AB  - To determine which of three published models best characterizes the factor
      structure of the Portuguese version of the Depression Anxiety Stress Scales-21
      and to assess its validity and reliability. Confirmatory factor analysis of
      Depression Anxiety and Stress Scale-21 for 1,297 adult, primary care outpatients
      (66.7% female, Mage = 48.57 years) comparing 3 models. The relationship between
      the Depression Anxiety Stress Scales-21 and the Positive and Negative Affect
      Schedule was analyzed. The correlated 3-factor model fit the data best. The scale
      demonstrated good internal consistency, with alpha scores of the subscales
      ranging from 0.836 to 0.897. Correlation with the Positive and Negative Affect
      Schedule was positive and moderate with the negative affect scale; it was
      negative and limited with the positive affect. These findings support the
      correlated 3-factor structure. The test demonstrated adequate reliability and
      construct validity, which supports its use for screening in primary care settings
      with Portuguese speakers.

PMID- 22991124
TI  - Falls in hospital settings: a longitudinal study.
AB  - This study aims to assess the prevalence of falls, understand their consequences,
      identify causes and analyze intervention strategies to prevent them. This is a
      descriptive longitudinal study, from 2007 to 2009, in which nurses recorded
      patients' falls in a medicine ward, using a scale developed for this end. Most
      falls occurred with partially dependent patients, with a mean age ranging from 64
      to 74 years. The bedroom was, in all of these years, the place where most of
      these falls occurred. Although most falls did not have consequences, they were
      observed in 36% of the cases. The number of falls increased throughout the years
      of the study. There was also a difference in the percentage of occurrences in the
      afternoon and night shifts (39% in 2007, 57% in 2008 and 64% in 2009). The
      identification of obstacles to referral and how to overcome them are analyzed
      here.

PMID- 22991125
TI  - Prevention of skin reactions due to teletherapy in women with breast cancer: a
      comprehensive review.
AB  - One of the possible courses of cancer treatment is teletherapy, and one of the
      most important adverse side effects are skin reactions, an ailment more commonly
      called radiodermatitis. The main purpose of this study is to analyze knowledge of
      the evidence about topical products used in the prevention of radiodermatitis, to
      support care delivery to women with breast cancer during teletherapy. The
      research method used here is the comprehensive literature review. Four databases
      were used to select the bibliography. The sample consists of 15 articles. The
      data shows that, among the topical products analyzed here, Calendula,
      corticosteroids and Xclair have shown significant protective effects, underlining
      their actions. The lack of articles published in Brazil highlights the need for
      further research in this area, seeking better care quality through the use of
      products with scientifically proven efficiency.

PMID- 22991126
TI  - Natural healers: a review of animal assisted therapy and activities as
      complementary treatment for chronic conditions.
AB  - The primary objective of this review is to synthesize the existing literature on
      the use of animal-assisted therapy and activity (AAT/A) as complementary
      treatment among people living with chronic disease and to discuss the possible
      application of this practice among children living with HIV. Relevant databases
      were searched between March 10 and April 11, 2011, using the words: animal
      assisted therapy or treatment and chronic conditions or diseases. Thirty-one
      articles were found and 18 followed the inclusion and exclusion criteria.
      Research suggests that AAT/A is effective for different patient profiles,
      particularly children. Interaction with dogs has been found to increase positive
      behaviors, such as sensitivity and focus, in children with social disabilities.
      Decreased levels of pain have also been reported among child patients as a result
      of AAT/A. More research should be done in the area of children living with
      chronic diseases that require strict adherence to treatment, such as HIV, and on
      AAT/A's prospective use as an educational tool to teach children about the
      importance of self-care for their medical conditions.

PMID- 22991127
TI  - Understanding the suffering of a patient with an illness: signs, context and
      strategies.
AB  - The aim of this study is to understand the suffering of a patient with an
      illness, by using a secondary research method, that is, a qualitative meta-study.
      The primary data source of the meta-study includes "biographical reports". This
      project is based on a case study, in which the first-hand experiences of a
      patient with an illness were collected. The findings of the reports were compiled
      using the Archivos de la Memoria collection of the Index Foundation (Granada,
      Spain) and journals specialized in editing these materials. A selection of 20
      biographical reports was targeted. The results of the meta-study show that
      suffering is a multidimensional process within a framework of ambiguous feelings.
      The suffering involves family and social network participation. Patients develop
      a range of strategies to overcome the illness. One of the effects is the fear of
      illness relapse or worsening.

PMID- 22991128
TI  - The herding hormone: oxytocin stimulates in-group conformity.
AB  - People often conform to others with whom they associate. Surprisingly, however,
      little is known about the possible hormonal mechanisms that may underlie in-group
      conformity. Here, we examined whether conformity toward one's in-group is altered
      by oxytocin, a neuropeptide often implicated in social behavior. After
      administration of either oxytocin or a placebo, participants were asked to
      provide attractiveness ratings of unfamiliar visual stimuli. While viewing each
      stimulus, participants were shown ratings of that stimulus provided by both in
      group and out-group members. Results demonstrated that on trials in which the
      ratings of the in-group and out-group were incongruent, the ratings of
      participants given oxytocin conformed to the ratings of their in-group but not of
      their out-group. Participants given a placebo did not show this in-group bias.
      These findings indicate that administration of oxytocin can influence subjective
      preferences, and they support the view that oxytocin's effects on social behavior
      are context dependent.

PMID- 22991130
TI  - Depression, anxiety and positive affect in people diagnosed with low-grade
      tumours: the role of illness perceptions.
AB  - OBJECTIVE: People with low-grade brain tumour experience a range of emotional,
      behavioural and psychosocial consequences. Using Leventhal's self-regulation
      model to explore biopsychosocial factors associated with distress, we examine the
      relationships between illness perceptions, coping and depression, anxiety and
      positive affect. METHODS: A cross-sectional, self-report study in which 74 people
      (54% women) diagnosed with a low-grade brain tumour completed the Illness
      Perceptions Questionnaire-Revised was conducted. Mean time since diagnosis was
      27.69 months (SD = 19.79). Mean age was 38.30 years (SD = 10.67). The Illness
      Perceptions Questionnaire-Revised, in addition to clinical, demographic and
      coping variables previously associated with psychological distress, was used to
      predict three psychological outcomes: depression, anxiety and positive affect.
      RESULTS: Hierarchical multiple regression analyses demonstrated that a
      biopsychosocial causal attribution was a significant predictor of anxiety and
      depression. Illness identity also emerged as a significant predictor of
      depression scores. Coping through self-blame was the only coping variable to
      emerge as a significant predictor of anxiety scores. A combination of coping
      through venting, acceptance, positive reframing, denial, behavioural
      disengagement and self-blame contributed to the variance in all three
      psychological outcome scores. No illness perception variables significantly
      predicted positive affect. CONCLUSIONS: Illness perceptions play a significant
      role in emotional distress experienced by people with low-grade brain tumours.
      Illness perceptions did not play a significant role in positive affect. Coping
      variables were shown to significantly contribute to the scores on all three
      psychological outcomes. Results suggest interventions targeted at modifying
      illness perceptions and enhancing problem-focused coping strategies may reduce
      psychological distress.

PMID- 22991131
TI  - The chemistry and biology of organic guanidine derivatives.
AB  - The chemistry and biology of organic natural guanidines are reviewed, including
      the isolation, structure determination, synthesis, biosynthesis and biological
      activities of alkaloids, non-ribosomal peptides, guanidine-bearing terpenes,
      polyketides and shikimic acid derivatives from natural sources.

PMID- 22991129
TI  - Early life stress and telomere length: investigating the connection and possible
      mechanisms: a critical survey of the evidence base, research methodology and
      basic biology.
AB  - How can adverse experiences in early life, such as maltreatment, exert such
      powerful negative effects on health decades later? The answer may lie in changes
      to DNA. New research suggests that exposure to stress can accelerate the erosion
      of DNA segments called telomeres. Shorter telomere length correlates with
      chronological age and also disease morbidity and mortality. Thus, telomere
      erosion is a potential mechanism linking childhood stress to health problems
      later in life. However, an array of mechanistic, methodological, and basic
      biological questions must be addressed in order to translate telomere discoveries
      into clinical applications for monitoring health and predicting disease risk.
      This paper covers the current state of the science and lays out new research
      directions.

PMID- 22991132
TI  - Perceived versus actual sedation practices in adult intensive care unit patients
      receiving mechanical ventilation.
AB  - BACKGROUND: With drug shortages, newer sedative medications, and updates in
      research, management of sedation and delirium in patients receiving mechanical
      ventilation continues to evolve. OBJECTIVE: To compare perceived and actual
      sedation practices for adults receiving mechanical ventilation in intensive care
      units (ICUs). METHODS: This was a multicenter, 2-part study conducted in adult
      ICUs in US hospitals. It included a sedation practice survey completed by ICU
      pharmacists and an observational study evaluating actual sedation practices over
      a 24-hour period. RESULTS: Surveys were completed for 85 ICUs; observational data
      for 496 patients were collected. Preferred sedatives from the survey data were
      propofol (short-term); propofol, midazolam, or lorazepam (intermediate); and
      lorazepam (long-term). Propofol was the most commonly used agent overall during
      the observational period (primarily for short-term and intermediate-length
      sedation); midazolam was the most commonly used for long-term sedation. Fentanyl
      was the preferred analgesic, and haloperidol and quetiapine were the preferred
      antipsychotics. Sedation treatment algorithms were used in only 50% of observed
      ICUs. Use of daily interruption of sedation was perceived to be 66% but was only
      observed in 36% of patients. Monitoring for delirium was reported among 25% of
      those surveyed but was observed in only 10% of patients. Targeted sedation goals
      were most frequently achieved when a treatment algorithm was used or when an
      opiate infusion was the single agent used for sedative management. CONCLUSIONS:
      These data suggest differences in perceived and actual sedation practice in the
      US, as well as underutilization of evidence-based interventions. Most notable was
      the limited use of sedation treatment algorithms, daily interruption of sedation,
      and monitoring for delirium. Individual sedation and delirium protocols should be
      evaluated and updated based on evidence-based recommendations.

PMID- 22991133
TI  - Treatment of levator ani syndrome with cyclobenzaprine.
AB  - OBJECTIVE: To report a case of levator ani syndrome (LAS) that was successfully
      treated with cyclobenzaprine. CASE SUMMARY: A 26-year-old male presented with a 3
      week history of severe, intermittent, aching anorectal pain that would last for
      30-60 minutes per episode and occurred between 1 and 3 times per day. The pain
      was aggravated by squatting, with no alleviating factors. Physical examination
      revealed no prostate tenderness, lesions, hemorrhoids, or fissures and rectal
      tone was intact. The patient had moderate posterior rectal tenderness. After a
      standard workup, he was diagnosed with LAS and treated with oral cyclobenzaprine
      5 mg 3 times daily for 7 days. The patient experienced resolution of his symptoms
      after 3 days of treatment and remained symptom-free 6 months after completion of
      therapy. The only reported adverse effect was mild drowsiness, which resolved
      after discontinuation of the cyclobenzaprine. DISCUSSION: A review of the
      literature via StatRef (April 1965-December 2011), Ovid (April 1965-December
      2011), and MEDLINE (April 1965-December 2011) reveals that existing treatment
      options for LAS have been limited to levator massage, sitz baths, nonsteroidal
      antiinflammatory drugs, diazepam, biofeed-back, botulinum toxin, steroid
      injections, and electrogalvanic stimulation, all of which offer minimal support.
      Cyclobenzaprine is a muscle relaxant; however, its mechanism of action is
      unclear. It is thought to influence the alpha and gamma motor neurons in the
      central nervous system, which leads to the attenuation of muscle spasm. To our
      knowledge, cyclobenzaprine has not been reported as a treatment for LAS. In our
      patient, however, the clinical efficacy of cyclobenzaprine was clearly apparent.
      CONCLUSIONS: Cyclobenzaprine effectively treated our patient's LAS. Given that
      cyclobenzaprine is safe, inexpensive, and shown to be effective in our case
      study, we believe it warrants further investigation as a first-line treatment
      option for LAS.

PMID- 22991134
TI  - Ezogabine: an evaluation of its efficacy and safety as adjunctive therapy for
      partial-onset seizures in adults.
AB  - OBJECTIVE: To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamic
      properties, and clinical application of ezogabine (retigabine, INN), an
      antiepileptic drug approved in 2011. DATA SOURCES: Published data from in vitro,
      animal, and clinical studies were obtained from PubMed and CINAHL searches, from
      January 1980 to March 31, 2012. Other relevant data regarding the safety and
      efficacy of ezogabine were obtained from the Food and Drug Administration and the
      European Medication Agency Web sites. STUDY SELECTION AND DATA EXTRACTION:
      Selected articles were prospective in vitro, animal, and controlled clinical
      studies of ezogabine. Non-English-language articles were excluded. DATA
      SYNTHESIS: In vitro and animal studies show that ezogabine activates voltagegated
      potassium channels, leading to reduction of seizure frequency by inhibiting
      hyperexcitability activity in the central nervous system. Additionally, ezogabine
      enhances gamma-aminobutyric acid (GABA) activity and de novo GABA synthesis.
      Eight clinical studies of ezogabine have been published, 5 being Phase 1 clinical
      trials in healthy subjects and 3 being Phase 3 clinical trials in patients with
      pharmaco-resistant partial-onset seizures. Phase 3 clinical trials demonstrated
      the safety and efficacy of ezogabine in patients with partial-onset seizures.
      CONCLUSIONS: Clinical trials have shown that ezogabine is efficacious as an
      adjunctive agent in patients with pharmacoresistant partial seizures. Careful
      monitoring of drug interactions and adverse reactions is necessary. While
      ezogabine is efficacious for partial seizures, its precise role in the management
      of patients with epilepsy is yet to be determined.

PMID- 22991135
TI  - Umbilical incision laparoscopic colectomy with one additional port for colorectal
      cancer.
AB  - BACKGROUND: Recently, laparoscopic colorectal surgery using a single incision
      usually made at the umbilical area has emerged as a tool to minimize the numbers
      of scars and provide better cosmetic results. But experience in laparoscopic
      skills is needed to maintain the oncologic principles of colorectal cancer
      surgery with the restricted operating field during the procedure. Adding an
      additional port to single-incision laparoscopic colorectal surgery (SILS) may be
      a bridge between conventional multiport laparoscopic surgery and SILS. The
      present study was undertaken to investigate whether umbilical incision
      laparoscopic colorectal cancer surgery with one additional port (ULAP) could be
      performed in a similar manner to conventional multiport surgery. METHODS: One
      hundred and sixty-three patients with colorectal adenocarcinoma underwent
      laparoscopic colectomy between February 2011 and August 2011. Forty of these
      patients underwent ULAP and were compared with the other 123 patients who had
      conventional laparoscopic surgery. Demographic, intraoperative, and postoperative
      data were analyzed. RESULTS: Both groups were similar in age (p = 0.438), gender
      (p = 0.818), body mass index (p = 0.149), American Society of Anesthesiologists
      (ASA) scores (p = 0.417), history of previous abdominal operation (p = 0.503),
      and tumor location (p = 0.051). Operation time was longer in the ULAP group
      (255.5 min) than in the conventional laparoscopic surgery group (144.6 min) (p <
      0.001). No significant differences were evident between groups for estimated
      blood loss (p = 0.263), transfusion requirements (p = 0.841), conversion to open
      procedures (p = 0.40), length of umbilical incisions (4.6 vs. 4.4 cm, p = 0.628),
      postoperative hospital stay (p = 0.862), tumor size (p = 0.455), number of
      harvested lymph nodes (p = 0.203), proximal margins (p = 0.189), and distal
      resection margins (p = 0.151). Postoperative morbidity (p = 0.736) was similar in
      both groups. There was no mortality postoperatively. CONCLUSIONS: Umbilical
      incision laparoscopic colorectal cancer surgery with an additional port is a
      feasible and safe approach, although it is more time consuming than conventional
      laparoscopic colectomy.

PMID- 22991136
TI  - VPS35 mutation in Japanese patients with typical Parkinson's disease.
AB  - Vacuolar protein sorting 35 (VPS35) was recently reported to be a pathogenic gene
      for late-onset autosomal dominant Parkinson's disease (PD), using exome
      sequencing. To date, VPS35 mutations have been detected only in whites with PD.
      The aim of the present study was to determine the incidence and clinical features
      of Asian PD patients with VPS35 mutations. We screened 7 reported nonsynonymous
      missense variants of VPS35, including p.D620N, known as potentially disease
      associated variants of PD, in 300 Japanese index patients with autosomal dominant
      PD and 433 patients with sporadic PD (SPD) by direct sequencing or high
      resolution melting (HRM) analysis. In addition, we screened 579 controls for the
      p.D620N mutation by HRM analysis. The p.D620N mutation was detected in 3 patients
      with autosomal dominant PD (1.0%), in 1 patient with SPD (0.23%), and in no
      controls. None of the other reported variants of VPS35 were detected. Haplotype
      analysis suggested at least 3 independent founders for Japanese patients with
      p.D620N mutation. Patients with the VPS35 mutation showed typical tremor
      predominant PD. We report Asian PD patients with the VPS35 mutation. Although
      VPS35 mutations are uncommon in PD, the frequency of such mutation is relatively
      higher in Japanese than reported in other populations. In VPS35, p.D620N
      substitution may be a mutational hot spot across different ethnic populations.
      Based on the clinical features, VPS35 should be analyzed in patients with PD,
      especially autosomal dominant PD or tremor-predominant PD.

PMID- 22991137
TI  - Sex and the single nucleotide polymorphism: exploring the genetic causes of
      skeletal sex differences.

PMID- 22991138
TI  - Application of high-throughput IEF-PAGE for EPO-doping testing.
AB  - Since its first publication in 2000, the isoelectric focusing (IEF) method of
      erythropoietin (EPO) used in doping control has been considered a procedure with
      relatively small sample number capacity. To overcome this limitation, a variation
      of the current protocol was evaluated, which uses double-sized gels with 48-120
      wells plus three electrodes and hence multiplies the capacity of the
      electrophoretic chamber. With this modification up to 120 samples and standards
      can be run on a single gel - thus, making IEF-PAGE of EPO a high-throughput
      method. The protocol is ideally suited for large-scale screening purposes.

PMID- 22991139
TI  - SUMOylation of ATF3 alters its transcriptional activity on regulation of TP53
      gene.
AB  - Cyclic AMP-dependent transcription factor-3 (ATF3), a stress sensor, plays an
      essential role in cells to maintain homeostasis and has diverse functions in
      cellular survival and death signal pathways. ATF3 is a novel regulator of p53
      protein stability and function. The activities of ATF3 are modulated by post
      translational modifications (PTMs), such as ubiquitination, but whether it is
      modified by small ubiquitin-related modifier (SUMO) remains unknown. The aim of
      this study was to investigate whether ATF3 is post-translationally modified by
      SUMO proteins and also to elucidate SUMOylation of ATF3 on TP53 gene activity.
      Here we report that ATF3 is clearly defined as a SUMO target protein both in
      vitro SUMOylation assay using recombinant proteins and at the cellular levels.
      Furthermore, ATF3 interacted with UBE2I, the only SUMO E2 enzyme found so far. In
      addition, PIAS3beta (a SUMO E3 ligase) enhanced and SENP2 and SENP7 (two
      SUMOylation proteases) decreased SUMOylation of ATF3, respectively. Finally, we
      found that ATF3 is selectively SUMOylated at lysine residue 42 but the
      SUMOylation does not alter subcellular localization of ATF3. We then
      characterized the functional role of ATF3 SUMOylation on TP53 gene expression. We
      found that SUMOylation of ATF3 is required for full repression of TP53 gene.
      Overall, we provide the first evidence that ATF3 is post-translationally modified
      by SUMO and SUMOylation of ATF3 plays a functional role in regulation of TP53
      gene activity.

PMID- 22991140
TI  - The roles of hypoxia-inducible factors in regulating neural stem cells migration
      to glioma stem cells and determinating their fates.
AB  - The mortality of patients with malignant gliomas remains high despite the
      advancement in multi-modal therapy including surgery, radio- and chemotherapy.
      Glioma stem cells (GSCs), sharing some characteristics with normal neural stem
      cells (NSCs), contribute to the cellular origin for primary gliomas and the
      recurrence of malignant gliomas after current conventional therapy. Accordingly,
      targeting GSCs proves to be a promising avenue of therapeutic intervention. The
      specific tropism of NSCs to GSCs provides a novel platform for targeted delivery
      of therapeutic agents. Tropism and mobilization of NSCs are enhanced by hypoxia
      through upregulating chemotactic cytokines and activating several signaling
      pathways. Moreover, hypoxia-inducible factors (HIFs) produced under hypoxic
      microenvironment of the stem cell niche play critical roles in the growth and
      stemness phenotypes regulation of both NSCs and GSCs. However, the definite
      cellular and molecular mechanisms of HIFs involvement in the process remain
      obscure. In this review, we focus on the pivotal roles of HIFs in migration of
      NSCs to GSCs and potential roles of HIFs in dictating the fates of migrated NSCs
      and targeted GSCs.

PMID- 22991142
TI  - Rehabilitation of walking after stroke.
AB  - OPINION STATEMENT: Rehabilitation of walking after stroke has been investigated
      with a variety of interventions, which will be outlined in this review. To date,
      the majority of interventions have demonstrated a positive, but similar effect in
      the primary clinical outcome of self-selected walking speed. Consistent among the
      most successful interventions is a focus on the intensity of the intervention and
      the ability to progress rehabilitation in a structured fashion. Successful
      progression of rehabilitation of walking likely lies in the ability to combine
      interventions based on an understanding of contributing underlying deficits (eg,
      motor control, strength, cardiovascular endurance, and dynamic balance).
      Rehabilitation programs must account for the need to train dynamic balance for
      falls prevention. Lastly, clinicians and researchers need to measure the effects
      of rehabilitation on participation and health related quality of life.

PMID- 22991143
TI  - Percutaneous interventional techniques to remove embolized silicone port
      catheters from heart and great vessels.
AB  - Rupture of a silicon port catheter is a relatively rare complication and
      sometimes it is difficult to remove it. We experienced three cases of retrieval
      of silicone port catheters migrating into cardiac ventricle or pulmonary artery.
      Several devices such as a snare wire, an ablation catheter, and a basket catheter
      in combination with interventional guiding catheter were applied to retrieve
      them. These interventional techniques are applicable for retrieval of embolized
      vascular access port system and other catheter fragments.

PMID- 22991141
TI  - Scaffolding proteins of the post-synaptic density contribute to synaptic
      plasticity by regulating receptor localization and distribution: relevance for
      neuropsychiatric diseases.
AB  - Synaptic plasticity represents the long lasting activity-related strengthening or
      weakening of synaptic transmission, whose well-characterized types are the long
      term potentiation and depression. Despite this classical definition, however, the
      molecular mechanisms by which synaptic plasticity may occur appear to be
      extremely complex and various. The post-synaptic density (PSD) of glutamatergic
      synapses is a major site for synaptic plasticity processes and alterations of PSD
      members have been recently implicated in neuropsychiatric diseases where an
      impairment of synaptic plasticity has also been reported. Among PSD members,
      scaffolding proteins have been demonstrated to bridge surface receptors with
      their intracellular effectors and to regulate receptors distribution and
      localization both at surface membranes and within the PSD. This review will focus
      on the molecular physiology and pathophysiology of synaptic plasticity processes,
      which are tuned by scaffolding PSD proteins and their close related partners,
      through the modulation of receptor localization and distribution at post-synaptic
      sites. We suggest that, by regulating both the compartmentalization of receptors
      along surface membrane and their degradation as well as by modulating receptor
      trafficking into the PSD, postsynaptic scaffolding proteins may contribute to
      form distinct signaling micro-domains, whose efficacy in transmitting synaptic
      signals depends on the dynamic stability of the scaffold, which in turn is
      provided by relative amounts and post-translational modifications of scaffolding
      members. The putative relevance for neuropsychiatric diseases and possible
      pathophysiological mechanisms are discussed in the last part of this work.

PMID- 22991144
TI  - Encephalopsin (OPN3) protein abundance in the adult mouse brain.
AB  - Encephalopsin belongs to the family of extraretinal opsins having a putative role
      in CNS tissue photosensitivity. Encephalopsin mRNA has earlier been localized in
      rodent brains, but expression and localization of the protein has not yet been
      reported. In this study, we aimed to define encephalopsin protein abundance and
      localization in the rodent brain. The distribution and localization of
      encephalopsin protein in a mouse brain and selected peripheral tissues were
      analysed in ten mice, using Western blotting and immunohistochemistry. The
      specificity of immunoreaction was validated by primary antibody omitting and
      immunizing peptide blocking experiment. We found encephalopsin protein abundant
      in the mouse brain, but not in the periphery. Encephalopsin protein was present
      in neurons of the mouse cerebral cortex, paraventricular area, and cerebellar
      cells. Our results show that encephalopsin is expressed at the protein level in
      different brain areas of the mouse. Therefore, the suggested idea that
      encephalopsin plays a role in non-visual photic processes seems to be applicable.
      Evidently, further investigations are needed to find out the signalling
      mechanisms, and the potential physiological role of encephalopsin in
      phototransduction due to the changes in ambient light.

PMID- 22991145
TI  - Comprehensive fluorogenic derivatization-liquid chromatography/tandem mass
      spectrometry proteomic analysis of colorectal cancer cell to identify biomarker
      candidate.
AB  - Existing colorectal cancer biomarkers are insufficient for providing a quick and
      accurate diagnosis, which is critical for a good prognosis. More appropriate
      biomarkers are thus needed. To identify new colorectal cancer biomarker
      candidates, we conducted a comprehensive differential proteomic analysis of six
      cancer cell lines and a normal cell line, utilizing a fluorogenic derivatization
      liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) approach. Two sets
      of intracellular biomarker candidates were identified: one for colorectal cancer,
      and the other for metastatic colorectal cancer. Our results suggest that
      cooperative expression of FABP5 and cyclophilin A might be linked to Her2
      signaling. Upregulation of LDHB and downregulation of GAPDH suggest the existence
      of a specific nonglycolytic energy production pathway in metastatic colorectal
      cancer cells. Downregulation of 14-3-3zeta/delta, cystatin-B, Ran and thioredoxin
      could be a result of their secretion, which then stimulates metastasis via
      activity in the sera and ascitic fluids. We propose a possible flow scheme to
      describe the dynamics of protein expression in colorectal cancer cells leading to
      tumor progression and metastasis via cell proliferation, angiogenesis,
      disorganization of actin filaments and epithelial-mesenchymal transition. Our
      results suggest that colorectal tumor progression may be regulated by signaling
      mediated by Her2, hypoxia, and TGFbeta.

PMID- 22991146
TI  - [From whale bone to endoscope - diagnosis and treatment of achalasia].

PMID- 22991148
TI  - [Consensus 2012--diagnosis and treatment of patients with dementia in
      Switzerland].

PMID- 22991149
TI  - [Cardiogenic pulmonary edema - truth and myths in the perspective of emergency
      medicine].
AB  - This critical analysis of the traditional pathophysiological approach to the
      diagnosis and treatment of cardiogenic pulmonary edema calls into question some
      long-established ideas and interventions that ought to be replaced by better
      evidence-based concepts.

PMID- 22991150
TI  - [Anemia in the elderly].
AB  - Anemia is common in the elderly and its impact on various important health
      outcomes has recently been clearly demonstrated. Although a causal relationship
      has not yet been demonstrated, adequate diagnosis and treatment are important.
      Because of ongoing changes in demographics an increasing number of anemic elderly
      patients is to be expected. Despite this, many issues regarding the aetiology and
      the management of anemia in older persons remain unresolved. The present review
      will focus on aspects specific to the causes of anemia in the elderly and
      suggests an algorithm for the management of this very common condition. Clearly
      evidence based guidelines on anemia in this highest age group need to be
      developed. Treatment options for patients with myelodysplastic syndromes are also
      discussed.

PMID- 22991151
TI  - [Varicose veins].

PMID- 22991152
TI  - [Sudden onset of abdominal distension...].
AB  - We report the case of a 39 years old patient with sudden onset of abdominal
      distension and icterus. Occlusion of the liver veins discovered by doppler
      ultrasound caused the portal hypertension and liver disease. Given the
      erythrocytosis the detection of JAK 2-mutation proved polycythemia vera as
      underlying disease for the Budd Chiari syndrome. The implantation of a TIPS
      wasn't successful because of an early thrombotic occlusion. Therefore a surgical
      mesocaval shunt was done. At the moment the patient is therapied with oral
      anticoagulation and hydroxycarbamide and is fully capable of work again.

PMID- 22991153
TI  - [Higher limits for d-dimer in older patients for thrombosis exclusion].

PMID- 22991154
TI  - [Factor Xa inhibitors are effectively the same as low molecular weight heparin in
      patients undergoing hip and knee replacement].

PMID- 22991158
TI  - Time-lapse imaging of the initiation of pollen embryogenesis in barley (Hordeum
      vulgare L.).
AB  - Pollen embryogenesis provides exciting opportunities in the areas of breeding and
      biotechnology as well as representing a convenient model for studying the process
      of plant cell proliferation in general and embryogenesis in particular. A cell
      culture system was devised in which immature barley pollen could be cultured as a
      monolayer trapped between the bottom glass-cover slip of a live-cell chamber and
      a diaphanous PTFE membrane within a liquid medium over a period of up to 28 d,
      allowing the process of embryogenesis to be tracked in individual pollen. Z
      stacks of images were automatically captured every 3min, starting from the
      unicellular pollen stage up to the development of multicellular, embryogenic
      structures. The method should prove useful for the elucidation of ultrastructural
      features and molecular processes associated with pollen embryogenesis.

PMID- 22991159
TI  - Cellular ion homeostasis: emerging roles of intracellular NHX Na+/H+ antiporters
      in plant growth and development.
AB  - Recent evidence highlights novel roles for intracellular Na(+)/H(+) antiporters
      (NHXs) in plants. The availability of knockouts and overexpressors of specific
      NHX isoforms has provided compelling genetic evidence to support earlier
      physiological and biochemical data which suggested the involvement of NHX
      antiporters in ion and pH regulation. Most plants sequenced to date contain
      multiple NHX members and, based on their sequence identity and localization, can
      be grouped into three distinct functional classes: plasma membrane, vacuolar, and
      endosomal associated. Orthologues of each functional class are represented in all
      sequenced plant genomes, suggesting conserved and fundamental roles across taxa.
      In this review we seek to highlight recent findings which demonstrate that
      intracellular NHX antiporters (i.e. vacuolar and endosomal isoforms) play roles
      in growth and development, including cell expansion, cell volume regulation, ion
      homeostasis, osmotic adjustment, pH regulation, vesicular trafficking, protein
      processing, cellular stress responses, as well as flowering. A significant new
      discovery demonstrated that in addition to the better known vacuolar NHX
      isoforms, plants also contain endosomal NHX isoforms that regulate protein
      processing and trafficking of cellular cargo. We draw parallels from close
      orthologues in yeast and mammals and discuss distinctive NHX functions in plants.

PMID- 22991160
TI  - An Arabidopsis gene encoding a C2H2-domain protein with alternatively spliced
      transcripts is essential for endosperm development.
AB  - The endosperm is an essential part of the seed which sustains embryo development
      and contains storage reserves. Endosperm development involves a series of nuclear
      divisions in the absence of cytokinesis. In this study, it is shown that a mutant
      Arabidopsis plant carrying the disrupted At4g24900 gene exhibits severe defects
      during seed development. At4g24900 encodes a nuclear-localized C2H2-containing
      protein and the transcripts of this gene are alternatively spliced, consequently
      producing at least nine differentially spliced isoforms. The heterozygous T-DNA
      insertion mutation in this gene resulted in abortion of 25% of seeds, and the
      homozygous mutant allele displayed embryo lethality. Differential interfernce
      contrast (DIC) analyses revealed that the mutant has endosperm nuclei with more
      than one nucleolus and an embryo arrested at the globular to heart stage
      transition. Because this mutant exhibits a titan-like phenotype, it was
      designated ttl. The TTL gene is preferentially expressed in tissues with quickly
      dividing cells as revealed in P(TTL)::GUS (beta-glucuronidase) transgenic plants.
      It is proposed that TTL is likely to function as a key regulator of endosperm
      nuclear division.

PMID- 22991161
TI  - Disrupting the bimolecular binding of the haem-binding protein 5 (AtHBP5) to haem
      oxygenase 1 (HY1) leads to oxidative stress in Arabidopsis.
AB  - The Arabidopsis thaliana L. SOUL/haem-binding proteins, AtHBPs belong to a family
      of five members. The Arabidopsis cytosolic AtHBP1 (At1g17100) and AtHBP2
      (At2g37970) have been shown to bind porphyrins and metalloporphyrins including
      haem. In contrast to the cytosolic localization of these haem-binding proteins,
      AtHBP5 (At5g20140) encodes a protein with an N-terminal transit peptide that
      probably directs targeting to the chloroplast. In this report, it is shown that
      AtHBP5 binds haem and interacts with the haem oxygenase, HY1, in both yeast two
      hybrid and BiFC assays. The expression of HY1 is repressed in the athbp5 T-DNA
      knockdown mutant and the accumulation of H(2)O(2) is observed in athbp5 seedlings
      that are treated with methyl jasmonate (MeJA), a ROS-producing stress hormone. In
      contrast, AtHBP5 over-expressing plants show a decreased accumulation of H(2)O(2)
      after MeJA treatment compared with the controls. It is proposed that the
      interaction between the HY1 and AtHBP5 proteins participate in an antioxidant
      pathway that might be mediated by reaction products of haem catabolism.

PMID- 22991162
TI  - Effects of an expressive writing intervention on cancer-related distress in
      Danish breast cancer survivors - results from a nationwide randomized clinical
      trial.
AB  - OBJECTIVE: To examine the effects of an expressive writing intervention (EWI) on
      cancer-related distress, depressive symptoms, and mood in women treated for early
      stage breast cancer. METHODS: A nationwide sample of 507 Danish women who had
      recently completed treatment for primary breast cancer were randomly assigned to
      three 20-min home-based writing exercises, one week apart, focusing on either
      emotional disclosure (EWI group) or a non-emotional topic (control group). Cancer
      related distress [Impact of Event Scale (IES)], depressive symptoms (Beck
      Depression Inventory-Short Form), and negative (37-item Profile of Moods State)
      and positive mood (Passive Positive Mood Scale) were assessed at baseline and at
      3 and 9 months post-intervention. Choice of writing topic (cancer versus other),
      alexithymia (20-item Toronto Alexithymia Scale), and social constraints (Social
      Constraints Scale) were included as possible moderators. RESULTS: Significant
      (p<0.01) group differences in mood change from before to immediately after each
      session suggested successful manipulation. Reductions over time in psychological
      symptoms were seen in both groups (p<0.05), but no time * group interactions were
      found. Choice of writing topic moderated effects on IES, with women writing about
      other themes showing greater reductions in cancer-related avoidance than women
      writing about their cancer. Fewer depressive symptoms and higher levels of
      positive mood were seen 3 months post-intervention in women writing about their
      cancer when compared with the control group. Difficulties describing feelings and
      externally oriented thinking (20-item Toronto Alexithymia Scale) moderated
      effects on positive mood and IES-total, while no moderating effects were found of
      social constraints. CONCLUSIONS: In concordance with the majority of previous
      results with cancer patients, no main effects of EWI were found for cancer
      related distress, depressive symptoms, and mood. Moderator analyses suggested
      that choice of writing topic and ability to process emotional experiences should
      be studied further.

PMID- 22991163
TI  - Cost-effectiveness of alendronate for the treatment of osteopenic postmenopausal
      women in Japan.
AB  - Many postmenopausal women have osteopenia, a condition characterized by loss of
      bone mineral density (BMD) that is not as severe as in osteoporosis. The
      objective of this study was to estimate the cost-effectiveness of alendronate to
      prevent fractures in osteopenic postmenopausal women without a history of
      fracture in Japan. An individual simulation model was developed to predict
      lifetime costs and quality-adjusted life years (QALYs) of 5 years of preventive
      alendronate therapy versus no preventive therapy. The risk of hip and vertebral
      fracture associated with age and BMD was derived from epidemiologic studies in
      Japan. We ran the model with different combinations of age (65, 70, and 75
      years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional
      clinical risk factors. For 70-year-old women with a BMD of 70% of the YAM having
      one of the following risk factors: a family history of hip fracture, high alcohol
      intake, or current smoking, the incremental cost-effectiveness ratio (ICER) of
      alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These
      results were sensitive to age, BMD, and number of clinical risk factors.
      Probabilistic sensitivity analysis for the base case showed that in the presence
      of one, two, and three risk factors, alendronate was cost-effective in 0.2% to
      2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is
      willing to pay $50,000 per QALY. Additional analysis indicated that alendronate
      can be a good value in osteopenic women if the 10-year probability for a
      osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate
      that whether to treat osteopenia with alendronate should be determined on the
      basis of age, BMD, and number of clinical risk factors in terms of cost
      effectiveness.

PMID- 22991164
TI  - Screening for congenital disorders of glycosylation in the first weeks of life.
AB  - Inherited monogenetic human disorders due to deficiencies in the complex
      metabolic pathways for N- and O-glycosylation of glycoconjugates are termed
      'congenital disorders of glycosylation' (CDG). Since the number of these defects
      with mostly severe multisystemic phenotypes has been rapidly expanding in recent
      years, the interest of paediatricians has also increased resulting in a rising
      amount of patient samples with the suspicion of CDG. In general, primary
      diagnostics for CDG start with investigations on the glycosylation state of serum
      transferrin, the 'gold standard' in the field for many years. However, the use of
      transferrin shows an analytical problem in the time span from birth up to the 3rd
      month of life. In this developmental period oligosaccharide moieties N-linked to
      proteins are often incomplete, resembling a CDG pattern and leading to false
      positive results. It is therefore necessary to establish a reliable and fast
      diagnostic procedure for this span of life. Here we show that the glycosylation
      state of serum alpha-1-antitrypsin is already fully existent shortly after birth
      allowing an alternative diagnostic approach for the investigation of CDG in the
      first weeks of life. The method can easily be established in every laboratory
      especially with previous experience in transferrin analysis. 

PMID- 22991165
TI  - Clinical and biochemical features associated with BCS1L mutation.
AB  - Our study describes a novel phenotype in a series of nine Saudi patients with
      lactic acidosis, from four consanguineous families three of which are related.
      Detailed genetic studies including linkage, homozygosity mapping and targeted
      sequencing identified a causative mutation in the BCS1L gene. All affected
      members of the families have an identical mutation in this gene, mutations of
      which are recognized causes of Bjornstad syndrome, GRACILE syndrome and a
      syndrome of neonatal tubulopathy, encephalopathy, and liver failure (MIM 606104)
      leading to isolated mitochondrial respiratory chain complex III deficiency. Here
      we report the appearance of a novel behavioral (five patients) and psychiatric
      (two patients) phenotype associated with a p.Gly129Arg BCS1L mutation, differing
      from the phenotype in a previously reported singleton patient with this mutation.
      The psychiatric symptoms emanated after childhood, initially as hypomania later
      evolving into intermittent psychosis. Neuroradiological findings included subtle
      white matter abnormalities, whilst muscle histopathology and respiratory chain
      studies confirmed respiratory chain dysfunction. The variable neuro-psychiatric
      manifestations and cortical visual dysfunction are most unusual and not reported
      associated with other BCS1L mutations. This report emphasizes the clinical
      heterogeneity associated with the mutation in BCS1L gene, even within the same
      family and we recommend that defects in this gene should be considered in the
      differential diagnosis of lactic acidosis with variable involvement of different
      organs. 

PMID- 22991167
TI  - Clinically relevant landmarks of the frontotemporal branch of the facial nerve: a
      three-dimensional study.
AB  - The frontotemporal branch of the facial nerve (FTN) is vulnerable during
      craniofacial surgeries due to its superficial course and variable distribution.
      Surface landmarks that correlate with the underlying course of the FTN can assist
      in surgical planning. Estimates of the course of FTN commonly rely on Pitanguy's
      line (PL), which utilizes variable soft-tissue landmarks. The purpose of this
      study was to evaluate palpable surface landmarks to predict the course and
      distribution of FTN using 3D modeling. Fifteen half-heads were used. In five
      formalin-embalmed specimens, surface topography was obtained using a FARO(r)
      scanner and landmarks corresponding to PL, porion, supraorbital notch,
      frontozygomatic and zygomaticotemporal sutures, and supraorbitomeatal line (SOML)
      and infraorbitomeatal line (IOML) were demarcated/digitized using a MicroscribeTM
      digitizer. A preauricular flap was raised, and branches of FTN were isolated and
      digitized. The data were reconstructed into 3D models (Geomagic(r)/Maya(r)) to
      quantify landmarks. In 10 Thiel-embalmed specimens, four independent raters
      identified/palpated and pinned the frontozygomatic and zygomaticotemporal sutures
      and PL. Data were collected and analyzed using the same protocol as in the first
      part of the study. Landmarking of PL was inconsistent between raters and not
      representative of FTN distribution. The easily identifiable surface landmarks
      defined in this study, a line 12 mm anterior to the porion along the SOML and
      IOML and a line joining the zygomaticotemporal and frontozygomatic sutures,
      comprehensively captured the distribution of FTN. The raters found a mean of 21
      +/- 2 branches between the lines out of a total of 22 +/- 2 branches. These
      landmarks may be used clinically to avoid injury to FTN.

PMID- 22991166
TI  - Plasma and urinary levels of dermatan sulfate and heparan sulfate derived
      disaccharides after long-term enzyme replacement therapy (ERT) in MPS I:
      correlation with the timing of ERT and with total urinary excretion of
      glycosaminoglycans.
AB  - INTRODUCTION: Mucopolysaccharidosis type I (MPS I) results in a defective
      breakdown of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate,
      which leads to a progressive disease. Enzyme replacement therapy (ERT) results in
      clearance of these GAGs from a range of tissues and can significantly ameliorate
      several symptoms. The biochemical efficacy of ERT is generally assessed by the
      determination of the total urinary excretion of GAGs. However, this has
      limitations. We studied the concentrations of heparan sulfate and dermatan
      sulfate derived disaccharides (HS and DS, respectively) in the plasma and urine
      of seven patients and compared these levels with total urinary GAGs (uGAGs)
      levels. METHODS: Plasma and urine samples were collected at different time points
      relative to the weekly ERT for three non-consecutive weeks in seven MPS I
      patients who had been treated with ERT for at least 2.5 years. Heparan and
      dermatan sulfate in plasma and urine were enzymatically digested into
      disaccharides, and HS and DS levels were determined by HPLC-MS/MS analysis. uGAGs
      were measured by the DMB test. RESULTS: The levels of HS and DS were markedly
      decreased compared with the levels before the initiation of ERT. However, the
      concentrations of DS in plasma and of both HS and DS in urine remained
      significantly elevated in all studied patients, while in six patients the level
      of total uGAGs had normalized. The concentrations of plasma and urinary HS during
      the weekly ERT followed a U-shaped curve. However, the effect size is small. The
      concentrations of plasma and urinary DS and uGAGs appeared to be in a steady
      state. CONCLUSIONS: HS and DS are sensitive biomarkers for monitoring the
      biochemical treatment efficacy of ERT and remain elevated despite long-term
      treatment. This finding may be related to the labeled dose or antibody status of
      the patient. The timing of the sample collection is not relevant, at least at the
      current dose of 100 IU/kg/weekly.

PMID- 22991168
TI  - A cadaveric study of the structural anatomy of the sternoclavicular joint.
AB  - Pathologies of the sternoclavicular (SC) joint are infrequent and effective
      management is often hindered by a limited understanding of the anatomy. In this
      study, we did macroscopic evaluations of the ligaments, the intra-articular disc,
      and the articulating surfaces of 25 SC joints. After removal of the joint
      capsule, the articulating surfaces of the sternal end of clavicle and the sternum
      were evaluated and the intra-articular disc was macroscopically examined. The
      anterior SC ligament covered the intra-articular disc, which divided the joint
      into a clavicular and a sternal part. A thin capsule, relatively lateral and
      medial from the anterior SC ligament, covered the two intra-articular parts. This
      means that the anterior SC ligament can be used as a landmark to enter into
      clavicular or sternal part of the SC joint. Posteriorly, there was a thick
      capsule without soft-spot or clear posterior SC ligament. Only the antero
      inferior surface of the sternal end of every clavicle was covered by cartilage.
      Of the intra-articular discs 56% were incomplete. All of these incomplete discs
      displayed a central hole with signs of degeneration and fraying. This was
      associated with increased cartilage degeneration at the clavicular side. By
      experimental design (past and present), it would seem reasonable to assume that
      the incomplete types are caused by degeneration and are not developmental.

PMID- 22991170
TI  - Near-total laryngectomy following failure after supracricoid partial
      laryngectomy.

PMID- 22991171
TI  - Recombinant laccase: I. Enzyme cloning and characterization.
AB  - We obtained structural and functional characterization of a recombinant Laccase
      from Rigidoporus lignosus (formerly Rigidoporus microporus), a white-rot
      basidiomycete, by means of circular dichroism (CD) spectra, cyclic voltammetry
      (CV) and biochemical assays. Here we report the optimization of expression and
      purification procedures of a recombinant Laccase expressed in supercompetent
      Escherichia coli cells. We amplified the coding sequence of Laccase using PCR
      from cDNA and cloned into a bacterial expression system. The resulting expression
      plasmid, pET-28b, was under a strong T7/Lac promoter induced by IPTG (isopropyl
      beta-d-thiogalactoipyranoside). We obtained purification by fast protein liquid
      chromatography (FPLC) method. We recorded the variation of the current of a
      solution containing purified Laccase with increasing Syringaldazine (SGZ)
      concentration using a potentiometer as proof of principle, showing its
      compatibility with the development of a new enzymatic biosensor for medical
      purposes, as described in Part II.

PMID- 22991172
TI  - Sweat testing for the detection of atomoxetine from paediatric patients with
      attention deficit/ hyperactivity disorder: application to clinical practice.
AB  - Atomoxetine (ATX) is a selective norepinephrine reuptake inhibitor approved since
      2002 for the treatment of attention deficit hyperactivity disorder (ADHD) in
      children, adolescents, and adults as an alternative treatment to methylphenidate.
      Within the framework of a project evaluating the use of alternative biological
      matrices for therapeutic monitoring of psychoactive drugs in paediatric and non
      paediatric individuals, the excretion of ATX and its principal metabolites has
      been recently studied in oral fluid and hair. The aim of this study was to
      describe the excretion profile of ATX and its metabolites 4-hydroxyatomoxetine (4
      OH-ATX) and N-desmethylatomoxetine (N-des-ATX) in sweat following the
      administration of different dosage regimens (60, 40, 35, and 18 mg/day) of ATX to
      six paediatric patients. Sweat patches were applied to the back of each
      participant and removed at timed intervals. ATX and its metabolites were measured
      in patches using a previously validated liquid chromatography-tandem mass
      spectrometric (LC-MS/MS) method. Independently from the administered dose, ATX
      appeared in the sweat patches 1 h post administration and reached its maximum
      concentration generally at 24 h. Peak ATX concentrations ranged between 2.31 and
      40.4 ng/patch and did not correlate with the administered drug dose, or with body
      surface area. Total ATX excreted in sweat ranged between 0.008 and 0.121 mg,
      corresponding to 0.02 and 0.3% of the administered drug. Neither 4-OH-ATX, nor N
      des-ATX was detected in either of the collected sweat patches. Measuring ATX in
      sweat patches can provide information on cumulative drug use from patch
      application until removal.

PMID- 22991173
TI  - Acute clenbuterol induces hypotension, atrioventricular block and cardiac
      asystole in the rabbit.
AB  - Clenbuterol is a long-lasting beta-adrenoceptor (beta-AR) agonist and was once
      medicated as a bronchial dilatator, and is also used by body-building enthusiasts
      and athletes and in livestock breeding because of its anabolic effect on skeletal
      muscles and ability to promote lipolysis. Though prohibited from pharmacological
      uses, clenbuterol intoxication cases are frequently reported, and most of the
      cardiac symptoms are tachyarrhythmia. Here, we reported a different
      cardiovascular toxic response to clenbuterol. Using a rabbit model, we tested the
      dose-response pattern of the cardiovascular system to intravenous administration
      of clenbuterol. Routine arterial blood pressure (BP) and surface
      electrocardiogram (ECG) were monitored. We observed that clenbuterol at a lower
      dose (0.4 mg/kg, n = 3) did not significantly affect the ECG, but decreased the
      mean BP roughly by 15-18 mmHg. At a medial dose (3.6 mg/kg, n = 3), clenbuterol
      induced significant hypotension (mean BP dropped by about 30 mmHg), first-degree
      atrioventricular (AV) block and intermittent ectopic activities with a relatively
      slow rate. The hypotension and arrhythmia recovered slowly, and animals did not
      die. Higher-dose clenbuterol (10 mg/kg, n = 6) induced severe hypotension, second
      degree AV block (Mobitz type II), 2:1 ventricular capture and progressive
      prolongations of P-R intervals and QRS duration, and the animals soon died of
      cardiac asystole. Different from other reports, we had not observed lethal
      tachyarrhythmia in all experiments except for the slight heart rate acceleration
      during the recovery stage of medial clenbuterol dosage. These results indicate
      that acute intravenous administration of clenbuterol has serious, dose-dependent
      cardiovascular toxicities and is even life threatening.

PMID- 22991174
TI  - Elevation of central arterial stiffness and vascular ageing in opiate withdrawal:
      cross-sectional and longitudinal studies.
AB  - The central cardiovascular impacts of clinical opiate withdrawal have not been
      explored in detail. Pulse Wave Analysis (SphygmoCor) was conducted in healthy
      controls and opiate-dependent populations. A total of 1,294 patients (69.2 %
      male) were studied in quintuplicate on 2,089 occasions. Four groups were studied:
      control (N = 576), buprenorphine stabilized (N = 592), withdrawal (N = 112) and
      severe withdrawal (N = 14). Control patients were younger than the other groups
      (29.96 +/- 0.45 years v. 32.53 +/- 0.74-39.28 +/- 3.86) but had similar sex
      ratios. Multiple regression was used to correct for the effects of age, and
      significant exacerbations were found in withdrawal in the vascular age (RA),
      augmentation index, subendocardial perfusion ratio (SEVR <100; R.R. 2.07 95 %
      C.I. 1.17-3.68, P = 0.02) and central systolic pressure both as factors
      themselves and in interactions with age (all P < 0.01). The elevation of modelled
      RA at 60 years was from 69.66 in controls to 97.54 in withdrawal (40.02 %). The
      effects on RA were found in both sexes and confirmed on longitudinal analysis.
      The elevation of RA in withdrawal was most marked after 40 years of age (P =
      0.027). These results show increased vascular stiffness and cardiovascular age
      but reduced subendocardial perfusion in opiate withdrawal. Given the daily
      recurrent nature of withdrawal, these effects are likely cumulative.

PMID- 22991176
TI  - UK fertilisation authority launches consultation on mitochondrial replacement
      techniques.

PMID- 22991175
TI  - GH-IGF system regulation of attenuated muscle growth and lipolysis in Atlantic
      salmon reared at elevated sea temperatures.
AB  - Growth regulation in adult Atlantic salmon (1.6 kg) was investigated during 45
      days in seawater at 13, 15, 17, and 19  degrees C. We focused on feed intake,
      nutrient uptake, nutrient utilization, and endocrine regulation through growth
      hormone (GH), insulin-like growth factors (IGF), and IGF-binding proteins
      (IGFBP). During prolonged thermal exposure, salmon reduced feed intake and
      growth. Feed utilization was reduced at 19  degrees C after 45 days compared with
      fish at lower temperatures, and body lipid storage was depleted with increasing
      water temperature. Although plasma IGF-1 concentrations did not change, 32-Da and
      43-kDa IGFBP increased in fish reared at <=17  degrees C, and dropped in fish
      reared at 19  degrees C. Muscle igf1 mRNA levels were reduced at 15 and 45 days
      in fish reared at 15, 17, and 19  degrees C. Muscle igf2 mRNA levels did not
      change after 15 days in response to increasing temperature, but were reduced
      after 45 days. Although liver igf2 mRNA levels were reduced with increasing
      temperatures after 15 and 45 days, temperature had no effect on igf1 mRNA levels.
      The liver igfbp2b mRNA level, which corresponds to circulating 43-kDa IGFBP,
      exhibited similar responses after 45 days. IGFBP of 23 kDa was only detected in
      plasma in fish reared at 17  degrees C, and up-regulation of the corresponding
      igfbp1b gene indicated a time-dependent catabolic response, which was not
      observed in fish reared at 19  degrees C. However, higher muscle ghr mRNA levels
      were detected in fish at 17 and 19  degrees C than in fish at lower temperatures,
      indicating lipolytic regulation in muscle. These results show that the reduction
      of muscle growth in large salmon is mediated by decreased igf1 and igf2 mRNA
      levels in addition to GH-associated lipolytic action to cope with prolonged
      thermal exposure. Accordingly, 13  degrees C appears to be a more optimal
      temperature for the growth of adult Atlantic salmon at sea.

PMID- 22991177
TI  - Elsevier improves access to its products in 100 developing countries.

PMID- 22991178
TI  - Serious complaints against doctors, suspensions, and erasures all fell in UK in
      2011.

PMID- 22991179
TI  - China is nearly ready to produce vaccines for developing world.

PMID- 22991180
TI  - Private firms are told that NHS in England is open for L20bn worth of business.

PMID- 22991182
TI  - The drive to ban the NOEC/LOEC in favor of ECx is misguided and misinformed.
AB  - Challenges to the use of the no observed effect concentration (NOEC) in
      ecotoxicology have appeared over the years, with a recent call for banning its
      use in favor of the x% effects concentration (ECx). This article presents an
      opposing view, providing reasons for the continued use of the NOEC, and for
      hypothesis testing in general. Although the use of ECx values is appropriate in
      many situations, there are numerous real-world examples where it is not suitable
      and offers no advantage over the use of hypothesis testing. These examples are
      presented with recommended data analysis techniques, illustrating the variety of
      statistical approaches that are meaningful in analyzing ecotoxicity data.
      Thoughtful consideration of study design and proper analysis and interpretation
      of the results will go further to advance the science of ecotoxicology than
      attempting to implement a blanket prohibition or endorsement of any single
      statistical approach.

PMID- 22991183
TI  - Direct medical resource utilization associated with osteoporosis-related
      nonvertebral fractures in postmenopausal women.
AB  - The purposes of this study were to assess direct medical resource utilization
      related to the treatment of nonvertebral osteoporotic fractures within 1 year
      postfracture and to evaluate whether age impacts resource utilization. A
      previously-validated algorithm for physician claims databases identified 15,327
      women aged 50 years or older with incident fracture at nonvertebral osteoporotic
      sites between January 1, 2004 and December 31, 2005. Administrative databases of
      the health services available to all residents in Quebec served to study fracture
      related health resource utilization in the year after fracture. Data were linked
      by a unique personal identifier, creating a longitudinal cohort of all fracture
      cases for health resource utilization. The proportions of fractures treated by
      open reduction, closed reduction, immobilization or follow-up by an orthopedic
      surgeon (OS) were evaluated. The mean number of claims for consultation with an
      OS or other clinicians in inpatient and outpatient visits, the hospitalization
      rate and length of stay (LOS) were assessed. Hip/femur fractures represented the
      highest rate of resource utilization because the majority of them required
      surgery (91.1%) and hospitalization (94.5%) with a mean (median) LOS of 39.2 (31)
      days. However, other nonvertebral fracture types needed significant clinical care
      related to surgery (27.9%), follow-up consultation with an OS (77.6%), and
      hospitalization (27.3% of total LOS). Even pelvic fractures, which often do not
      require surgical treatment, commanded high resource utilization due to the high
      hospitalization rate (67.4%) with mean (median) LOS of 34.2 (26) days. Moreover,
      age was an important determinant of health resource utilization, being associated
      with an increased number of visits to other physicians, hospitalization, and
      length of hospitalization (LOS), admissions to long term care (LTC), and death.
      Osteoporosis-related fractures accounted for substantial healthcare resource
      utilization. With an aging population and increased prevalence of fractures,
      strategies for osteoporosis management need to be introduced to reduce the
      healthcare burden.

PMID- 22991184
TI  - Determination of reduced folates in tumor and adjacent mucosa of colorectal
      cancer patients using LC-MS/MS.
AB  - A liquid chromatography electrospray ionization tandem mass spectrometry (LC
      MS/MS) method has been developed for the determination of 5,10
      methylenetetrahydrofolate (methyleneTHF), tetrahydrofolate (THF) and 5
      methyltetrahydrofolate (methylTHF) in colorectal mucosa and tumor tissues. The
      folate extraction method includes homogenization, heat and folate conjugase
      treatment to hydrolyze polyglutamyl folate to monoglutamyl folate. Before
      analysis on LC-MS/MS, simple and fast sample purification with ultrafiltration
      (molecular weight cut-off membrane, 10 kDa) was performed. Folates were detected
      and quantified using positive electrospray. The method described in the present
      paper was successfully applied to determine the level of three folate
      monoglutamates in mucosa and tumor samples from 77 colorectal cancer patients,
      starting from a limited amount of tissue. The results showed that the LC-MS/MS
      method has a great advantage over other previously used methods because of its
      high sensitivity and selectivity. Significantly higher levels of methyleneTHF and
      THF were found in tumor compared with matched mucosa tissues. Folate levels in
      adjacent mucosa were associated with tumor location, age and gender. The
      correlation between folate levels and tumor site further strengthens the fact
      that development of right- and left-sided tumors follows different pathways.

PMID- 22991185
TI  - Impact of vitamin D3 on cardiovascular responses to glucocorticoid excess.
AB  - Although the cardiovascular system is not a classical target for 1,25
      dihydroxyvitamin D3, both cardiac myocytes and vascular smooth muscle cells
      respond to this hormone. The present study aimed to elucidate the effect of
      active vitamin D3 on cardiovascular functions in rats exposed to glucocorticoid
      excess. Adult male Wistar rats were allocated into three groups: control group,
      dexamethasone (Dex)-treated group receiving Dex (200 MUg/kg) subcutaneously for
      12 days, and vitamin D3-Dex-treated group receiving 1,25-(OH)2D3 (100 ng/kg) and
      Dex (200 MUg/kg) subcutaneously for 12 days. Rats were subjected to measurement
      of systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures and
      heart rate. Rate pressure product (RPP) was calculated. Rats' isolated hearts
      were perfused in Langendorff preparation and studied for basal activities (heart
      rate, peaked developed tension, time to peak tension, half relaxation time, and
      myocardial flow rate) and their responses to isoproterenol infusion. Blood
      samples were collected for determination of plasma level of nitrite, nitric oxide
      surrogate. Dex-treated group showed significant increase in SBP, DBP, MAP, and
      RPP, as well as cardiac hypertrophy and enhancement of basal cardiac performance
      evidenced by increased heart rate, rapid and increased contractility, and
      accelerated lusitropy, together with impaired contractile and myocardial flow
      rate responsiveness to beta-adrenergic activation and depressed inotropic and
      coronary vascular reserves. Such alterations were accompanied by low plasma
      nitrite. These changes were markedly improved by vitamin D3 treatment. In
      conclusion, vitamin D3 is an efficacious modulator of the deleterious
      cardiovascular responses induced by glucocorticoid excess, probably via
      accentuation of nitric oxide.

PMID- 22991186
TI  - Solid-phase synthesis and screening of a library of C-terminal arginine peptide
      aldehydes against Murray Valley encephalitis virus protease.
AB  - Murray Valley encephalitis virus is a member of the flavivirus group, a large
      family of single-stranded RNA viruses, which cause serious disease in all regions
      of the world. Unfortunately, no suitable antivirals are available, and there are
      commercial vaccines for only three flaviviruses. The solid-phase synthesis of a
      library of 400 C-terminal arginine peptide aldehydes and their screening against
      Murray Valley encephalitis virus protease are demonstrated. The library was
      utilised to elucidate several tripeptide sequences that can be used as inhibitors
      in further SAR studies.

PMID- 22991187
TI  - Thermoacoustic sound generation from monolayer graphene for transparent and
      flexible sound sources.
AB  - Transparent and flexible loudspeakers are realized with large-area monolayer
      graphene. The acoustic performances are characterized according to the supporting
      substrate effect and geometrical configurations. The substrate effect on the
      thermoacoustic sound generation from graphene is studied by controlling the
      surface porosity of various substrates.

PMID- 22991188
TI  - Investigations on hydrogen isotope ratios of endogenous urinary steroids:
      reference-population-based thresholds and proof-of-concept.
AB  - Carbon isotope ratio (CIR) analysis has been routinely and successfully used in
      sports drug testing for many years to uncover the misuse of endogenous steroids.
      One limitation of the method is the availability of steroid preparations
      exhibiting CIRs equal to endogenous steroids. To overcome this problem, hydrogen
      isotope ratios (HIR) of endogenous urinary steroids were investigated as a
      potential complement; results obtained from a reference population of 67
      individuals are presented herein. An established sample preparation method was
      modified and improved to enable separate measurements of each analyte of interest
      where possible. From the fraction of glucuronidated steroids; pregnanediol, 16
      androstenol, 11-ketoetiocholanolone, androsterone (A), etiocholanolone (E),
      dehydroepiandrosterone (D), 5alpha- and 5beta-androstanediol, testosterone and
      epitestosterone were included. In addition, sulfate conjugates of A, E, D,
      epiandrosterone and 17alpha- and 17beta-androstenediol were considered and
      analyzed after acidic solvolysis. The obtained results enabled the calculation of
      the first reference-population-based thresholds for HIR of urinary steroids that
      can readily be applied to routine doping control samples. Proof-of-concept was
      accomplished by investigating urine specimens collected after a single oral
      application of testosterone-undecanoate. The HIR of most testosterone metabolites
      were found to be significantly influenced by the exogenous steroid beyond the
      established threshold values. Additionally, one regular doping control sample
      with an extraordinary testosterone/epitestosterone ratio of 100 without
      suspicious CIR was subjected to the complementary methodology of HIR analysis.
      The HIR data eventually provided evidence for the exogenous origin of urinary
      testosterone metabolites. Despite further investigations on HIR being advisable
      to corroborate the presented reference-population-based thresholds, the developed
      method proved to be a new tool supporting modern sports drug testing procedures.

PMID- 22991189
TI  - miR-200c enhances radiosensitivity of human breast cancer cells.
AB  - Due to the intrinsic resistance of many tumors to radiotherapy, current methods
      to improve the survival of cancer patients largely depend on increasing tumor
      radiosensitivity. It is well-known that miR-200c inhibits epithelial-mesenchymal
      transition (EMT), and enhances cancer cell chemosensitivity. We sought to clarify
      the effects of miR-200c on the radiosensitization of human breast cancer cells.
      In this study, we found that low levels of miR-200c expression correlated with
      radiotolerance in breast cancer cells. miR-200c overexpression could increase
      radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by
      increasing apoptosis and DNA double-strand breaks. Additionally, we found that
      miR-200c directly targeted TANK-binding kinase 1 (TBK1). However, overexpression
      of TBK1 partially rescued miR-200c mediated apoptosis induced by ionizing
      radiation. In summary, miR-200c can be a potential target for enhancing the
      effect of radiation treatment on breast cancer cells.

PMID- 22991190
TI  - Laryngeal pathologies in older Korean adults and their association with smoking
      and alcohol consumption.
AB  - OBJECTIVES/HYPOTHESIS: This study's objectives were to assess the prevalence rate
      of laryngeal pathologies in the Korean elderly, and to examine the association of
      smoking and alcohol consumption with laryngeal diseases. STUDY DESIGN: Cross
      sectional study. METHODS: Data were from the 2008 Korea National Health and
      Nutritional Examination Survey. Subjects were 663 elderly persons (261 men and
      402 women) between the ages of 65 and 84 years who completed the laryngoscopic
      examination. Weighted prevalence of laryngeal pathologies was compared by
      demographic characteristics, smoking, alcohol drinking, body mass index, and self
      reported voice problems. Multiple logistic regression analyses were conducted to
      examine the independent as well as combined influence of smoking and alcohol
      consumption on laryngeal lesions. RESULTS: The prevalence of laryngeal
      pathologies in the Korean elderly between the ages of 65 and 84 years was 8.1%.
      The prevalence of laryngeal lesions increased with age and was higher among men,
      middle school and high school graduates, manual workers, current smokers, current
      alcohol drinkers, and those with self-reported voice problems. Adjusting for
      covariates, current smokers, compared with nonsmokers, were more likely to have
      laryngeal pathologies (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.01
      4.67). Current alcohol drinking was not independently associated with laryngeal
      diseases. Concurrent smoking and alcohol drinking, however, were associated with
      a significantly higher risk of laryngeal pathologies (OR, 3.29; 95% CI, 1.22
      8.88). CONCLUSIONS: Smoking and alcohol consumption may increase the risk of
      laryngeal diseases in later life.

PMID- 22991191
TI  - Pre-operative embolisation of choroid plexus tumours in children. Part II.
      Observations on the effects on CSF production.
AB  - OBJECTIVE: Choroid plexus tumours are one of the few causes of hydrocephalus
      secondary to increased CSF production. Operative treatment aided by pre-op
      embolisation is being used in our institution as a primary option of treatment.
      Our aim was firstly to quantify the effects of embolisation on CSF production and
      secondly to assess whether the use of pre-operative embolisation would lead to
      reduction of CSF production thus reducing the need for CSF diversion procedures
      in the perioperative and long term. METHODS: From 1996 till 2009, 30 patients
      (mean age, 2.25 years) underwent surgical treatment for 24 choroid plexus
      papillomas and 6 choroid plexus carcinomas. Thirteen underwent pre-operative
      super-selective embolisation of the feeding vessels with Histoacryl glue. The
      need for CSF diversion-external ventricular drain (EVD)/shunt-was recorded
      together with the daily CSF production between the two groups (embolised: EMB+
      vs. not embolised: EMB-) RESULTS: The embolisation was successful in 13 of 15
      (86.6 %) patients. The average post-op daily CSF production between the EMB+ and
      EMB- groups was (67 vs. 135 ml/day; p = 0.005). EVD days in situ post-operatively
      was 7.9 vs. 12.1 (p = 0.033). However, the need for permanent CSF diversion was
      similar in both groups (five vs. six). CONCLUSION: We have established the safety
      of pre-operative embolisation as an adjunct to operative treatment of choroid
      plexus tumours. As we expected, this technique, by removing the tumour's blood
      supply, reduces the rate of CSF production. This has had a positive impact on the
      post-operative management of these patients. We cannot say the same for the need
      of permanent CSF diversion in our study.

PMID- 22991192
TI  - Human apolipoprotein E isoforms differentially affect bone mass and turnover in
      vivo.
AB  - The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of
      lipoproteins. However, a new role for apoE as a regulator of bone metabolism in
      mice has recently been established. In contrast to mice, the human APOE gene is
      characterized by three common isoforms APOE epsilon2, epsilon3, and epsilon4 that
      result in different metabolic properties of the apoE isoforms, but it remains
      controversial whether the APOE polymorphism influences bone traits in humans. To
      clarify this, we investigated bone phenotypes of apoE knock-in (k.i.) mice, which
      express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of
      the mouse apoE. Analysis of 12-week-old female k.i. mice revealed increased
      levels of biochemical bone formation and resorption markers in apoE2 k.i. animals
      as compared to apoE3 k.i. and apoE4 k.i., with a reduced osteoprotegerin
      (OPG)/receptor activator of NF-kappaB ligand (RANKL) ratio in apoE2 k.i.,
      indicating increased turnover with prevailing resorption in apoE2 k.i.
      Accordingly, histomorphometric and micro-computed tomography (uCT) analyses
      demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and
      apoE4 k.i. animals, which was reflected by a significant reduction of lumbar
      vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical
      thickness, and stability was not differentially affected by the apoE isoforms. To
      extend these observations to the human situation, plasma from middle-aged healthy
      men homozygous for epsilon2/epsilon2, epsilon3/epsilon3, and epsilon4/epsilon4 (n
      = 21, n = 80, n = 55, respectively) was analyzed with regard to bone turnover
      markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in
      the serum of epsilon2/epsilon2 carriers as compared to epsilon3/epsilon3 and
      epsilon4/epsilon4 individuals (p = 0.02 for epsilon2/epsilon2 versus
      epsilon4/epsilon4). In conclusion, the current data strongly underline the
      general importance of apoE as a regulator of bone metabolism and identifies the
      APOE epsilon2 allele as a potential genetic risk factor for low trabecular bone
      mass and vertebral fractures in humans.

PMID- 22991193
TI  - Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal
      reorganization.
AB  - Type I phosphatidylinositol-4-phosphate 5-kinase (PIPKI) is the main enzyme
      generating the lipid second messenger phosphatidylinositol-4,5-bisphosphate
      [PI(4,5)P2], which has critical functions in many cellular processes, such as
      cytoskeletal reorganization, membrane trafficking, and signal transduction. All
      three members of the PIPKI family are activated by phosphatidic acid (PA).
      However, how PA regulates the activity and functions of PIPKI have not been fully
      elucidated. In this study, we identify a PA-binding site on PIPKIgamma. Mutation
      of this site inhibited the PA-stimulated activity and membrane localization of
      PIPKIgamma as well as the formation of actin comets and foci induced by
      PIPKIgamma. We also demonstrate that phospholipase D (PLD) generates a pool of PA
      involved in PIPKIgamma regulation by showing that PLD inhibitors blocked the
      membrane localization of PIPKIgamma and its ability to induce actin cytoskeletal
      reorganization. Targeting the PIPKIgamma PA-binding-deficient mutant to membranes
      by a membrane localization sequence failed to restore the actin reorganization
      activity of PIPKIgamma, suggesting that PA binding is not only involved in
      recruiting PIPKIgamma to membranes but also may induce a conformational change.
      Taken together, these results reveal a new molecular mechanism through which PA
      regulates PIPKI and provides direct evidence that PA is important for the
      localization and functions of PIPKI in intact cells.

PMID- 22991195
TI  - Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with
      intracranial vascular malformation of the Dyke-Davidoff-Masson type in two
      patients.
AB  - The term twin spotting refers to phenotypes characterized by the spatial and
      temporal co-occurrence of two (or more) different nevi arranged in variable
      cutaneous patterns, and can be associated with extra-cutaneous anomalies. Several
      examples of twin spotting have been described in humans including nevus
      vascularis mixtus, cutis tricolor, lesions of overgrowth, and deficient growth in
      Proteus and Elattoproteus syndromes, epidermolytic hyperkeratosis of Brocq, and
      the so-called phacomatoses pigmentovascularis and pigmentokeratotica. We report
      on a 28-year-old man and a 15-year-old girl, who presented with a previously
      unrecognized association of paired cutaneous vascular nevi of the
      telangiectaticus and anemicus types (naevus vascularis mixtus) distributed in a
      mosaic pattern on the face (in both patients) and over the entire body (in the
      man) and a complex brain malformation (in both patients) consisting of cerebral
      hemiatrophy, hypoplasia of the cerebral vessels and homolateral hypertrophy of
      the skull and sinuses (known as Dyke-Davidoff-Masson malformation). Both patients
      had facial asymmetry and the young man had facial dysmorphism, seizures with EEG
      anomalies, hemiplegia, insulin-dependent diabetes mellitus (IDDM), autoimmune
      thyroiditis, a large hepatic cavernous vascular malformation, and left Legg-Calve
      Perthes disease (LCPD) [LCPD-like presentation]. Array-CGH analysis and mutation
      analysis of the RASA1 gene were normal in both patients.

PMID- 22991194
TI  - C2 domain membrane penetration by group IVA cytosolic phospholipase A2 induces
      membrane curvature changes.
AB  - Group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) is an 85 kDa enzyme that
      regulates the release of arachidonic acid (AA) from the sn-2 position of membrane
      phospholipids. It is well established that cPLA(2)alpha binds zwitterionic lipids
      such as phosphatidylcholine in a Ca(2+)-dependent manner through its N-terminal
      C2 domain, which regulates its translocation to cellular membranes. In addition
      to its role in AA synthesis, it has been shown that cPLA(2)alpha promotes
      tubulation and vesiculation of the Golgi and regulates trafficking of endosomes.
      Additionally, the isolated C2 domain of cPLA(2)alpha is able to reconstitute Fc
      receptor-mediated phagocytosis, suggesting that C2 domain membrane binding is
      sufficient for phagosome formation. These reported activities of cPLA(2)alpha and
      its C2 domain require changes in membrane structure, but the ability of the C2
      domain to promote changes in membrane shape has not been reported. Here we
      demonstrate that the C2 domain of cPLA(2)alpha is able to induce membrane
      curvature changes to lipid vesicles, giant unilamellar vesicles, and membrane
      sheets. Biophysical assays combined with mutagenesis of C2 domain residues
      involved in membrane penetration demonstrate that membrane insertion by the C2
      domain is required for membrane deformation, suggesting that C2 domain-induced
      membrane structural changes may be an important step in signaling pathways
      mediated by cPLA(2)alpha.

PMID- 22991196
TI  - Too frequent use of painkillers can cause rather than cure headaches.

PMID- 22991197
TI  - Increased apoptosis induction in hepatocellular carcinoma by a novel tumor
      targeted TRAIL fusion protein combined with bortezomib.
AB  - As the result of an increasing incidence and a prevalent therapy resistance of
      hepatocellular carcinoma (HCC), there is a strong need for novel strategies to
      enhance treatment responses in HCC. Tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) has been proposed as a promising anticancer drug because
      it can selectively induce apoptosis in cancer cells, but not in healthy cells.
      Nevertheless, most tumor cells show TRAIL resistance, emphasizing the requirement
      for apoptosis-sensitizing agents and TRAIL molecules with improved tumor
      specificity. In this study, we employed a recombinant TRAIL molecule, in which
      three TRAIL protomers were expressed as a single polypeptide chain (scTRAIL), and
      a novel TRAIL variant, in which scTRAIL was additionally fused to an antibody
      fragment recognizing epidermal growth factor receptor (EGFR) to improve its HCC
      targeting properties. We analyzed the proapoptotic effects of both TRAIL versions
      in combination with the proteasome inhibitor bortezomib (BZB) in hepatoma cells
      and primary human hepatocytes as well as in intact explants from HCC and healthy
      liver tissue. We demonstrate that EGFR-targeted TRAIL in combination with BZB
      induced significantly higher caspase activation and cell death in hepatoma cells,
      but not in primary hepatocytes. Importantly, when incubated with fresh liver
      explants, the combination of EGFR-targeted TRAIL and BZB displayed selective
      cytotoxicity for HCC, but not for tumor-free liver tissue, which could even be
      verified in liver explants from the same individuals. Unlike nontargeted TRAIL,
      EGFR-targeted TRAIL combined with BZB exerted no toxicity in liver tissues from
      nonalcoholic fatty liver disease patients. CONCLUSION: EGFR-targeted TRAIL
      reveals increased antitumor activity toward HCC without inducing toxicity to
      tumor-free liver tissue and might therefore represent a promising novel strategy
      for HCC treatment.

PMID- 22991198
TI  - Mechanically strong, optically transparent, giant metal superlattice
      nanomembranes from ultrathin gold nanowires.
AB  - Metallic membranes of about 2.5 nm thick but with macroscopic lateral dimensions
      have been successfully fabricated from ultrathin gold nanowires. Such metallic
      nanomembranes are transparent, conductive and mechanically strong, with an
      optical transmittance of 90-97%, an electrical resistance of ~1142 kOmega sq(-1)
      , and a breaking strength of ~14 N m(-1)  with a typical atomic force microscope
      probe.

PMID- 22991199
TI  - A mouse neurodegenerative dynein heavy chain mutation alters dynein motility and
      localization in Neurospora crassa.
AB  - Cytoplasmic dynein is responsible for the transport and delivery of cargoes in
      organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due
      to mutations in dynein or its activating complex dynactin can result in one of
      several neurological diseases in mammals. The mouse Legs at odd angles (Loa)
      mutation in the tail domain of the dynein heavy chain has been shown to lead to
      progressive neurodegeneration in mice. The mechanism by which the Loa mutation
      affects dynein function is just beginning to be understood. In this work, we
      generated the dynein tail mutation observed in Loa mice into the Neurospora
      crassa genome and utilized cell biological and complementing biochemical
      approaches to characterize how that tail mutation affected dynein function. We
      determined that the Loa mutation exhibits several subtle defects upon dynein
      function in N. crassa that were not seen in mice, including alterations in dynein
      localization, impaired velocity of vesicle transport, and in the biochemical
      properties of purified motors. Our work provides new information on the role of
      the tail domain on dynein function and points out areas of future research that
      will be of interest to pursue in mammalian systems.

PMID- 22991201
TI  - Reply to Falk and Clarke on Taung virtual endocast midline and volume.

PMID- 22991202
TI  - Phthalate is associated with insulin resistance in adipose tissue of male rat:
      role of antioxidant vitamins.
AB  - Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of
      products, including lubricants, perfumes, hairsprays and cosmetics, construction
      materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine
      disruptor and it has a continuum of influence on various organ systems in human
      beings and experimental animals. However, specific effects of DEHP on insulin
      signaling in adipose tissue are not known. Adult male albino rats of Wistar
      strain were divided into four groups. Control, DEHP treated (dissolved in olive
      oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through
      gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and
      C (100 mg/kg body weight) dissolved in olive oil and distilled water,
      respectively, once daily through gastric intubations for 30 days. After the
      completion of treatment, adipose tissue was dissected out to assess various
      parameters. DEHP treatment escalated H(2)O(2) and hydroxyl radical levels as well
      as lipid peroxidation in the adipose tissue. DEHP impaired the expression of
      insulin signaling molecules and their phosphorelay pathways leading to diminish
      plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation.
      Blood glucose level was elevated as a result of these changes. Supplementation of
      vitamins (C & E) prevented the DEHP-induced changes. It is concluded that DEHP
      induced ROS and lipid peroxidation disrupts the insulin signal transduction in
      adipose tissue and favors glucose intolerance. Antioxidant vitamins have a
      protective role against the adverse effect of DEHP.

PMID- 22991203
TI  - Effect of pulsed electromagnetic fields on human osteoblast cultures.
AB  - BACKGROUND AND PURPOSE: Exogenous electromagnetic fields (EMFs) affect bone
      metabolism, but the mechanisms responsible for this phenomenon are unclear.
      Pulsed EMFs (PEMFs) can be effective in the management of congenital
      pseudarthrosis or delayed union or non-union of fractures. We investigated the
      effects of PEMFs used in clinical practice on human osteoblast cultures. METHODS:
      Primary osteoblastic cells were isolated from a human femoral head. Cultures were
      exposed to the PEMF stimulation for 72 hours, 7 and 10 days and compared with a
      control group of primary osteoblastic cells non-exposed to PEMF. Cell growth and
      alkaline phosphatase activity were evaluated in the osteoblast cell cultures at
      each observation time. RESULTS: At each observation time, the differences in cell
      numbers between PEMF-exposed cells and control group were statistically
      significant (p < 0.05). The alkaline phosphatase-specific activity of PEMF
      exposed osteoblast cultures showed a statistically significant (p < 0.05)
      increase when compared with the control group after 7 and 10 days of exposure.
      CONCLUSIONS: The application of PEMF stimulation on human osteoblasts accelerates
      cellular proliferation when compared with a control group of non-PEMF-exposed
      cells.

PMID- 22991200
TI  - Regulation of late endosomal/lysosomal maturation and trafficking by cortactin
      affects Golgi morphology.
AB  - Cortactin is a branched actin regulator and tumor-overexpressed protein that
      promotes vesicular trafficking at a variety of cellular sites, including
      endosomes and the trans-Golgi network. To better understand its role in secretory
      trafficking, we investigated its function in Golgi homeostasis. Here, we report
      that knockdown (KD) of cortactin leads to a dramatic change in Golgi morphology
      by light microscopy, dependent on binding the Arp2/3 actin-nucleating complex.
      Surprisingly, there was little effect of cortactin-KD on anterograde trafficking
      of the constitutive cargo vesicular stomatitis virus glycoprotein (VSVG), Golgi
      assembly from endoplasmic reticulum membranes upon Brefeldin A washout, or Golgi
      ultrastructure. Instead, electron microscopy studies revealed that cortactin-KD
      cells contained a large number of immature-appearing late endosomal/lysosomal
      (LE/Lys) hybrid organelles, similar to those found in lysosomal storage diseases.
      Consistent with a defect in LE/Lys trafficking, cortactin-KD cells also exhibited
      accumulation of free cholesterol and retention of the retrograde Golgi cargo
      mannose-6-phosphate receptor in LE. Inhibition of LE maturation by treatment of
      control cells with Rab7 siRNA or chloroquine led to a compact Golgi morphology
      similar to that observed in cortactin-KD cells. Furthermore, the Golgi morphology
      defects of cortactin-KD cells could be rescued by removal of cholesterol
      containing lipids from the media, suggesting that buildup of cholesterol-rich
      membranes in immature LE/Lys induced disturbances in retrograde trafficking.
      Taken together, these data reveal that LE/Lys maturation and trafficking are
      highly sensitive to cortactin-regulated branched actin assembly and suggests that
      cytoskeletal-induced Golgi morphology changes can be a consequence of altered
      trafficking at late endosomes.

PMID- 22991204
TI  - Surgical correction of tracheo-oesophageal fistula and oesophageal atresia in
      infants with VACTERL association: a retrospective case-control study.
AB  - INTRODUCTION: VACTERL is a rare, non-random association comprising at least three
      major component features defined by the acronym, and including Vertebral
      anomalies, Anorectal malformations, Cardiac defects, Tracheo-oEsophageal fistula
      with or without oesophageal atresia (TOF/OA), Renal abnormalities and Limb
      anomalies. The aim of this study was to compare the post-operative outcomes
      following surgical correction of TOF/OA in infants with VACTERL and isolated
      TOF/OA. METHODS: A retrospective case-control study comparing infants with
      VACTERL (case group) versus infants with isolated TOF/OA (control group) that
      underwent surgical correction of TOF/OA at our centre between January 2006 and
      December 2011. Patient demographics, types of anomalies, operative techniques and
      post-operative outcomes were collected using inpatient and outpatient records.
      RESULTS: We identified 30 consecutive infants with TOF/OA. Five infants had
      VACTERL (17 %) and 15 infants had isolated TOF/OA (50 %). There was no
      significant difference in the gestational age (P = 0.79), birth weight (P = 0.69)
      or operative repair (P = 0.14) between groups. Overall, surgical correction of
      TOF/OA led to satisfactory morbidity. Infants with VACTERL were not at higher
      risk of post-operative complications, such as oesophageal stricture (P = 0.17) or
      gastro-oesophageal reflux (P = 1.0), compared to infants with isolated TOF/OA.
      CONCLUSIONS: VACTERL association does not increase the risk of post-operative
      complications following TOF/OA repair.

PMID- 22991205
TI  - The role of laparoscopy in the treatment of duodenal obstruction in term and
      preterm infants.
AB  - PURPOSE: The aim of this study was to evaluate the role of laparoscopy in the
      surgical treatment of intrinsic and extrinsic duodenal lesions referring to the
      underlying cause of obstruction. METHODS: Retrospective chart review of all cases
      of duodenal obstructions undergoing surgery at our institution between April 2004
      and March 2012. RESULTS: Twenty patients underwent surgery for duodenal
      obstruction (11 female, 9 male). Seven infants were born prematurely. Eleven
      infants had extrinsic, seven had intrinsic and two had a combination of intrinsic
      and extrinsic duodenal lesions. A laparoscopic procedure was initially started in
      18 of 20 patients (90 %). Thirteen of the 18 infants (72 %) underwent various
      laparoscopic procedures: laparoscopic duodenoduodenostomy, resection of a
      duodenal membrane and the transsection of Ladd's bands. In five patents, a
      conversion became necessary due to poor visualisation of the duodenum. In three
      patients (15 %) with extrinsic duodenal lesion a reoperation was necessary. Two
      of the 20 patients (10 %) were operated with an "open" approach to begin with.
      CONCLUSION: Laparoscopy is feasible and safe in most cases. The few conversions
      were early in the series due to a lack of experience and necessitated by poor
      visualisation, most often caused by malrotation.

PMID- 22991206
TI  - Proteomic analysis of high NaCl-induced changes in abundance of nuclear proteins.
AB  - Mammalian cells are normally stressed by high interstitial NaCl in the renal
      medulla and by lesser elevation of NaCl in several other tissues. High NaCl
      damages proteins and DNA and can kill cells. Known protective responses include
      nuclear translocation of the transcription factor NFAT5 and other proteins. In
      order better to understand the extent and significance of changes in nuclear
      protein abundance, we extracted nuclear and cytoplasmic proteins separately from
      HEK293 cells and measured by LC-MS/MS (iTRAQ) changes of abundance of proteins in
      the extracts in response to high NaCl at three time points: 1 h, 8 h, and adapted
      for two passages. We confidently identified a total of 3,190 proteins; 163
      proteins changed significantly at least at one time point in the nucleus. We
      discerned the biological significance of the changes by Gene Ontology and protein
      network analysis. Proteins that change in the nucleus include ones involved in
      protein folding and localization, microtubule-based process, regulation of cell
      death, cytoskeleton organization, DNA metabolic process, RNA processing, and cell
      cycle. Among striking changes in the nucleus, we found a decrease of all six 14-3
      3 isoforms; dynamic changes of "cytoskeletal" proteins, suggestive of
      nucleoskeletal reorganization; rapid decrease of tubulins; and dynamic changes of
      heat shock proteins. Identification of these changes of nuclear protein abundance
      enhances our understanding of high NaCl-induced cellular stress, and provides
      leads to previously unknown damages and protective responses.

PMID- 22991207
TI  - Dietary fat source alters hepatic gene expression profile and determines the type
      of liver pathology in rats overfed via total enteral nutrition.
AB  - To determine if dietary fat composition affects the progression of nonalcoholic
      fatty liver disease (NAFLD), we overfed male Sprague-Dawley rats low (5%) or high
      (70%) fat diets with different fat sources: olive oil (OO), corn oil (CO), or
      echium oil (EO), with total enteral nutrition (TEN) for 21 days. Overfeeding of
      the 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P < 0.05).
      Affymetrix array analysis revealed significant differences in hepatic gene
      expression signatures associated with greater fatty acid synthesis, ChREBP, and
      SREBP-1c signaling and increased fatty acid transport (P < 0.05) in the 5% OO
      compared with 5% CO group. The OO groups had macrosteatosis, but no evidence of
      oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro
      and macrosteatosis or only microsteatosis, respectively; increased oxidative
      stress; and increased necrotic injury relative to their respective 5% groups (P <
      0.05). Oxidative stress and necrosis correlated with increasing peroxidizability
      of the accumulated triglycerides. Affymetrix array analysis comparing the 70% OO
      and 70% CO groups revealed increased antioxidant pathways and lower expression of
      genes linked to inflammation and fibrosis in the 70% OO group. A second study in
      which 70% OO diet was overfed for 50 days produced no evidence of progression of
      injury beyond simple steatosis. These data suggest that dietary fat type strongly
      influences the progression of NAFLD and that a Mediterranean diet high in olive
      oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis.

PMID- 22991209
TI  - Transcriptional responses to hypoxia are enhanced by recurrent hypoxia (hypoxic
      preconditioning) in the epaulette shark.
AB  - All animals require molecular oxygen for aerobic energy production, and oxygen
      availability has played a particularly important role in the evolution of aquatic
      animals. This study investigates how previous exposure to hypoxia
      (preconditioning) primes protective transcriptional responses in a hypoxia
      tolerant vertebrate species, the epaulette shark (Hemiscyllium ocellatum). The
      epaulette shark is a basal cartilaginous fish that in its natural environment
      experiences cyclic hypoxic periods. We evaluated whether the transcription of a
      set of crucial prosurvival genes is affected differently by a single short-term
      (2 h) exposure to sublethal hypoxia compared with eight such successive hypoxia
      exposures (hypoxia preconditioning). We discovered that hypoxia preconditioning
      amplifies transcriptional responses compared with animals that experienced a
      single hypoxic bout. In the heart we observed that hypoxic preconditioning, but
      not a single hypoxic exposure, resulted in higher transcript levels of genes that
      regulate oxygen and energy homeostasis, including those of hypoxia-inducible
      factor-1 alpha, adenosine signaling pathway components, and genes affecting
      circulation [prostaglandin synthetase 2 (cox-2) and natriuretic peptide C]. This
      suggests that in a single short-term hypoxic bout, the responses to low oxygen
      are regulated at the level of pre-existing proteins or translational and
      posttranslational machinery, whereas transcriptional responses are induced in
      experiments that parallel the natural environmental cycles of oxygen
      availability. These findings have general implications for understanding how
      vertebrates regulate protective gene expression upon physiological stress.

PMID- 22991208
TI  - Controlled reoxygenation cardiopulmonary bypass is associated with reduced
      transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing
      surgery.
AB  - In cyanotic patients undergoing repair of heart defects, high level of oxygen
      during cardiopulmonary bypass (CPB) leads to greater susceptibility to myocardial
      ischemia and reoxygenation injury. This study investigates the effects of
      controlled reoxygenation CPB on gene expression changes in cyanotic hearts of
      patients undergoing surgical correction of tetralogy of Fallot (TOF). We
      randomized 49 cyanotic TOF patients undergoing corrective cardiac surgery to
      receive either controlled reoxygenation or hyperoxic/standard CPB. Ventricular
      myocardium biopsies were obtained immediately after starting and before
      discontinuing CPB. Microarray analyses were performed on samples, and array
      results validated with real-time PCR. Gene expression profiles before and after
      hyperoxic/standard CPB revealed 35 differentially expressed genes with three
      upregulated and 32 downregulated. Upregulated genes included two E3 Ubiquitin
      ligases. The products of downregulated genes included intracellular signaling
      kinases, metabolic process proteins, and transport factors. In contrast, gene
      expression profiles before and after controlled reoxygenation CPB revealed only
      11 differentially expressed genes with 10 upregulated including extracellular
      matrix proteins, transport factors, and one downregulated. The comparison of gene
      expression following hyperoxic/standard vs. controlled reoxygenation CPB revealed
      59 differentially expressed genes, with six upregulated and 53 downregulated.
      Upregulated genes included PDE1A, MOSC1, and CRIP3. Downregulated genes
      functionally clustered into four major classes: extracellular matrix/cell
      adhesion, transcription, transport, and cellular metabolic process. This study
      provides direct evidence that hyperoxic CPB decreases the adaptation and
      remodeling capacity in cyanotic patients undergoing TOF repair. This simple CPB
      strategy of controlled reoxygenation reduced the number of genes whose expression
      was altered following hyperoxic/standard CPB.

PMID- 22991210
TI  - An economic evaluation: Simulation of the cost-effectiveness and cost-utility of
      universal prevention strategies against osteoporosis-related fractures.
AB  - A patient-level Markov decision model was used to simulate a virtual cohort of
      500,000 women 40 years old and over, in relation to osteoporosis-related hip,
      clinical vertebral, and wrist bone fractures events. Sixteen different screening
      options of three main scenario groups were compared: (1) the status quo (no
      specific national prevention program); (2) a universal primary prevention
      program; and (3) a universal screening and treatment program based on the 10-year
      absolute risk of fracture. The outcomes measured were total directs costs from
      the perspective of the public health care system, number of fractures, and
      quality-adjusted life-years (QALYs). Results show that an option consisting of a
      program promoting physical activity and treatment if a fracture occurs is the
      most cost-effective (CE) (cost/fracture averted) alternative and also the only
      cost saving one, especially for women 40 to 64 years old. In women who are 65
      years and over, bone mineral density (BMD)-based screening and treatment based on
      the 10-year absolute fracture risk calculated using a Canadian Association of
      Radiologists and Osteoporosis Canada (CAROC) tool is the best next alternative.
      In terms of cost-utility (CU), results were similar. For women less than 65 years
      old, a program promoting physical activity emerged as cost-saving but BMD-based
      screening with pharmacological treatment also emerged as an interesting
      alternative. In conclusion, a program promoting physical activity is the most CE
      and CU option for women 40 to 64 years old. BMD screening and pharmacological
      treatment might be considered a reasonable alternative for women 65 years old and
      over because at a healthcare capacity of $50,000 Canadian dollars ($CAD) for each
      additional fracture averted or for one QALY gained its probabilities of cost
      effectiveness compared to the program promoting physical activity are 63% and
      75%, respectively, which could be considered socially acceptable. Consideration
      of the indirect costs could change these findings.

PMID- 22991211
TI  - Spectrum of immune-mediated inner ear disease and cochlear implant results.
AB  - OBJECTIVES/HYPOTHESIS: To characterize the progression of hearing loss in
      patients with immune-mediated inner ear disease (IMIED), and to identify disease-
      and patient-specific factors associated with cochlear implant (CI) performance.
      STUDY DESIGN: Retrospective cohort study. METHODS: Subjects consisted of CI
      patients suspected to have lost their hearing due to IMIED. The primary dependent
      variable for functional decline was time to deafness, whereas for CI benefit it
      was post-CI speech perception scores. Independent variables included presence or
      absence of systemic autoimmune disease, age at CI, and insertion depth of the
      cochlear electrode. RESULTS: A transient favorable response to immunosuppressive
      therapy was reported in 16 of 26 patients (66.67%). The time to deafness differed
      between an organ (ear)-specific immune-mediated group, a systemic immune-mediated
      group including Cogan syndrome and relapsing polychondritis (subgroup A), and a
      systemic immune-mediated group associated with other autoimmune diseases
      (subgroup B; P = .001). Disease group (-15.52; P = .04), insertion depth of the
      CI electrode (40.71; P = .01), and the age at CI (-0.48, P = .05) were associated
      with speech perception results. CONCLUSIONS: Triaging IMIED cases based on
      presence and type of systemic autoimmune disease may aid in selecting a
      management strategy. Knowledge about the predictors of CI outcome will help
      clinicians select appropriate patients for CIs. In the setting of significant and
      irreversible hearing deficit, the restoration of hearing using a cochlear
      prosthesis may be appropriate earlier rather than later.

PMID- 22991212
TI  - Disease-specific databases: why we need them and some recommendations from the
      Human Variome Project Meeting, May 28, 2011.
AB  - The need for Locus-Specific Databases, with disease-specific experts and
      curators, is an essential ingredient in a process to enable the benefits of the
      advances in sequencing and mutational analysis to be realized across the genome.
      Next generation sequencing provides both astounding opportunities and challenges,
      especially for genetic counsellors. An approach coordinated at a genome wide,
      international level, supported by well-organized disease-specific respected
      organizations is a model most likely to be successful, but committed resourceful
      professionals working in local poorly resourced environments can make valuable
      contributions that can grow. Bioinformatic tools to sift and integrate multiple
      domains of information are being developed, and play a major part in meeting the
      challenges. Regulation of providers, including a requirement for them to submit
      mutational information to central databases, also should assist to reach the
      goals needed to realize the opportunities. There is also a need to agree on
      governance of Locus-Specific Databases (LSDBs) at an international level, and for
      adequate international funding to support this need, to ensure humanity reaps the
      benefits of the current molecular genetic revolution. The Human Variome Project
      offers this, working also with the other major initiatives with similar
      objectives. This report concludes with Recommendations for the Human Variome
      Project stemming from the presentations and discussions at the meeting.

PMID- 22991213
TI  - Histone lysine methyltransferase, suppressor of variegation 3-9 homolog 1,
      promotes hepatocellular carcinoma progression and is negatively regulated by
      microRNA-125b.
AB  - Hepatocellular carcinoma (HCC) is a major liver malignancy. We previously
      demonstrated that deregulation of epigenetic regulators is a common event in
      human HCC. Suppressor of variegation 3-9 homolog 1 (SUV39H1), the prototype of
      histone methyltransferase, is the major enzyme responsible for histone H3 lysine
      9 trimethylation, which, essentially, is involved in heterochromatin formation,
      chromosome segregation, and mitotic progression. However, the implication of
      SUV39H1 in hepatocarcinogenesis remains elusive. In this study, we found that
      SUV39H1 was frequently up-regulated in human HCCs and was significantly
      associated with increased Ki67 expression (P < 0.001) and the presence of venous
      invasion (P = 0.017). To investigate the role of SUV39H1 in HCC development, both
      gain- and loss-of-function models were established. SUV39H1 overexpression
      remarkably enhanced HCC cell clonogenicity, whereas knockdown of SUV39H1
      substantially suppressed HCC cell proliferation and induced cell senescence. In
      addition, ectopic expression of SUV39H1 increased the migratory ability of HCC
      cells, whereas a reduced migration rate was observed in SUV39H1 knockdown cells.
      The significance of SUV39H1 in HCC was further demonstrated in a nude mice model;
      SUV39H1 knockdown drastically inhibited in vivo tumorigenicity and abolished
      pulmonary metastasis of HCC cells. We also identified microRNA-125b (miR-125b) as
      a post-transcriptional regulator of SUV39H1. Ectopic expression of miR-125b
      inhibited SUV39H1 3'-untranslated-region-coupled luciferase activity and
      suppressed endogenous SUV39H1 expression at both messenger RNA and protein
      levels. We have previously reported frequent down-regulation of miR-125b in HCC.
      Interestingly, miR-125b level was found to be inversely correlated with SUV39H1
      expression (P = 0.001) in clinical specimens. Our observations suggested that miR
      125b down-regulation may account for the aberrant SUV39H1 level in HCC.
      CONCLUSION: Our study demonstrated that SUV39H1 up-regulation contributed to HCC
      development and metastasis. The tumor-suppressive miR-125b served as a negative
      regulator of SUV39H1.

PMID- 22991214
TI  - Wide-range refractive index control of organic semiconductor films toward
      advanced optical design of organic optoelectronic devices.
AB  - A large refractive index difference of 0.58 is demonstrated in organic
      semiconductor films toward advanced optical design of organic optoelectronic
      devices. Efficient control of light propagation is shown by distributed Bragg
      reflectors (DBRs) consisting of organic semiconductor films. The DBRs also show
      photoconductivity, indicating the promising possibility of active control of both
      charges and light by the organic semiconductors themselves.

PMID- 22991215
TI  - Teasing, depression and unhealthy weight control behaviour in obese children.
AB  - BACKGROUND: Data were taken from 80 obese children (mean age = 10.03 years; mean
      body mass index = 27.37; %white = 29.37%; %female = 58.8%). Self-report surveys
      were used to collect data on rates of depressive symptoms, unhealthy weight
      control behaviours (UWCBs), teasing, sources of teasing and how much the teasing
      bothered the child. OBJECTIVES: This study aimed to evaluate relationships
      between weight-related teasing and UWCBs and depression in obese children.
      Teasing by peers and/or family, negative feelings due to teasing, frequency of
      teasing, and number of teasing sources reported and associations with UWCBs and
      depression were analysed. METHODS: Logistical and linear regressions were used to
      evaluate relationships between the teasing variables, depression and UWCBs,
      controlling for age and gender. RESULTS: Results indicated that children teased
      by other children have significantly higher levels of depression (B = 6.1 [SE =
      2.3]) and are five times more likely to engage in UWCBs (OR = 5.1 [CI = 1.5
      17.4]). Children who endorsed that teasing by peers bothered them had
      significantly higher levels of depression (B = 2.3 [SE = 0.8]). The frequency of
      weight-related teasing was significantly associated with depression (B = 2.5 [SE
      = 0.8]), as was the number of teasing sources (B = 4.6 [SE = 1.5]). No
      significant relationships were found between familial teasing and depression or
      UWCBs. CONCLUSIONS: Weight-related teasing, especially by other children, was
      associated with negative psychosocial measures in these obese children.
      Interventions are needed to reduce teasing, and longitudinal studies are
      recommended to understand the impact of teasing over time.

PMID- 22991216
TI  - Model selection, zero-inflated models, and predictors of primate abundance in
      Korup National Park, Cameroon.
AB  - Determining the ecological and anthropogenic factors that shape the abundance and
      distribution of wild primates is a critical component of primate conservation
      research. Such research is complicated, however, whenever the species under study
      are encountered infrequently, a characteristic of many taxa that are threatened
      with extinction. Typically, the resulting data sets based on surveys of such
      species will have a high frequency of zero counts which makes it difficult to
      determine the predictor variables that are associated with species abundance. In
      this study, we test various statistical models using survey data that was
      gathered on seven species of primate in Korup National Park, Cameroon. Predictor
      variables include hunting signs and aspects of habitat structure and floristic
      composition. Our statistical models include zero-inflated models that are
      tailored to deal with a high frequency of zero counts. First, using exploratory
      data analysis we found the most informative set of models as ranked by Delta-AIC
      (Akaike's information criterion). On the basis of this analysis, we used five
      predictor variables to construct several regression models including Poisson,
      zero-inflated Poisson, negative binomial, and zero-inflated negative binomial.
      Total basal area of all trees, density of secondary tree species, hunting signs,
      and mean basal area of all trees were significant predictors of abundance in the
      zero-inflated models. We discuss the statistical logic behind zero-inflated
      models and provide an interpretation of parameter estimates. We recommend that
      researchers explore a variety of models when determining the factors that
      correlate with primate abundance.

PMID- 22991217
TI  - Medication intensification in diabetes in rural primary care: a cluster
      randomised effectiveness trial.
AB  - OBJECTIVE: To determine the effectiveness of a provider-based intervention to
      improve medication intensification among patients with diabetes. DESIGN:
      Effectiveness cluster-randomised trial. Baseline and follow-up cross-sections of
      diabetes physicians' patients. SETTING: Eleven U.S. Southeastern states, 2006
      2008. PARTICIPANTS: 205 Rural primary care physicians, 95 completed the study.
      INTERVENTION: Multicomponent interactive intervention including web-based
      continuing medical education (CME), performance feedback and quality improvement
      tools. PRIMARY OUTCOME MEASURES: Medication intensification, a dose increase of
      an existing medication or the addition of a new class of medication for glucose,
      blood pressure and lipids control on any of the three most recent office visits.
      RESULTS: Of 364 physicians attempting to register, 102 were randomised to the
      intervention and 103 to the control arms; 95 physicians (intervention, n=48;
      control, n=47) provided data on their 1182 of their patients at baseline
      (intervention, n=715; control, n=467) and 945 patients at follow-up
      (intervention, n=479; control, n=466). For A1c control, medication
      intensification increased in both groups (intervention, pre 26.4% vs post 32.6%,
      p=0.022; control, pre 24.8% vs post 31.1%, p=0.033) (intervention, adjusted OR
      (AOR) 1.37; 95% CI 1.06 to 1.76; control, AOR 1.41 (95% CI 1.06 to 1.89));
      however, we observed no incremental benefit solely due to the intervention (group
      by-time interaction, p=0.948). Among patients with the worst glucose control (A1c
      >9%), intensification increased in both groups (intervention, pre 34.8% vs post
      62.5%, p=0.002; control, pre 35.7% vs post 61.4%, p=0.008). CONCLUSIONS: A wide
      reach, low-intensity, web-based interactive multicomponent intervention had no
      significant incremental effect on medication intensification for control of
      glucose, blood pressure or lipids for patients with diabetes of physicians
      practising in the rural Southeastern USA. TRIAL REGISTRATION: NCT00403091.

PMID- 22991221
TI  - Increased presence of capillaries next to remodeling sites in adult human
      cancellous bone.
AB  - Vascularization is a prerequisite for osteogenesis in a number of situations,
      including bone development, fracture healing, and cortical bone remodeling. It is
      unknown whether a similar link exists between cancellous bone remodeling and
      vascularization. Here, we show an association between remodeling sites,
      capillaries, proliferative cells, and putative osteoblast progenitors. Iliac
      crest biopsies from normal human individuals were subjected to histomorphometry
      and immunohistochemistry to identify the respective positions of bone remodeling
      sites, CD34-positive capillaries, smooth muscle actin (SMA)-positive putative
      osteoblast progenitors, including pericytes, Ki67-positive proliferative cells,
      and bone remodeling compartment (BRC) canopies. The BRC canopy is a recently
      described structure separating remodeling sites from the bone marrow, consisting
      of CD56-positive osteoblasts at an early differentiation stage. We found that
      bone remodeling sites were associated with a significantly increased presence of
      capillaries, putative osteoblast progenitors, and proliferative cells in a region
      within 50 um of the bone or the canopy surface. The increases were the highest
      above eroded surfaces and at the level of the light-microscopically assessed
      contact of these three entities with the bone or canopy surfaces. Between 51 and
      100 um, their densities leveled to that found above quiescent surfaces. Electron
      microscopy asserted the close proximity between BRC canopies and capillaries
      lined by pericytes. Furthermore, the BRC canopy cells were found to express SMA.
      These ordered distributions support the existence of an osteogenic-vascular
      interface in adult human cancellous bone. The organization of this interface fits
      the current knowledge on the mode of action of vasculature on osteogenesis, and
      points to the BRC canopy as a central player in this mechanism. We propose a
      model where initiation of bone remodeling coincides with the induction of
      proximity of the vasculature to endosteal surfaces, thereby allowing capillary
      BRC canopy interactions that activate marrow events, including recruitment of
      osteoblast progenitors to bone remodeling sites.

PMID- 22991218
TI  - A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar
      ATPase through its homeodomain.
AB  - LASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned
      by our laboratory from non-metastatic and metastatic cancer cell variants of
      human prostate carcinoma PC-3M using mRNA differential display in 1999.
      LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V-ATPase,
      ATP6V0C) and regulate V-ATPase activity. In an attempt to provide molecular
      mechanism of the interaction between LASS2/TMSG1 and V-ATPase, we constructed
      four variant transfectants containing different functional domain of LASS2/TMSG1
      and stably transfected the variants to human prostate cancer cell line PC-3M-1E8
      cell with high metastatic potential. Results showed that there were no obvious
      differences of V-ATPase expression among different transfected cells and the
      control. However, V-ATPase activity and intracellular pH was significantly higher
      in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the
      control using the pH-dependent fluorescence probe BECEF/AM. Immunoprecipitation,
      immunofluorescence and immuno-electron microscope alone or in combination
      demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C.
      Loss of Homeodomain markedly enhanced the proliferation ability but weakened the
      apoptotic effect of LASS2/TMSG1 in PC-3M-1E8 cells. These lines of results for
      the first time contribute to the conclusion that LASS2/TMSG1 could regulate V
      ATPase activity and intracellular pH through the direct interaction of its
      Homeodomain and the C subunit of V-ATPase. Their interaction could play important
      roles in the apoptosis of tumor cells.

PMID- 22991222
TI  - An inherited LMNA gene mutation in atypical Progeria syndrome.
AB  - Hutchinson-Gilford Progeria syndrome (HGPS) is a rare genetic disorder,
      characterized by several clinical features that begin in early childhood,
      recalling an accelerated aging process. The diagnosis of HGPS is based on the
      recognition of common clinical features and detection of the recurrent
      heterozygous c.1824C>T (p.Gly608Gly) mutation within exon 11 in the Lamin A/C
      encoding gene (LMNA). Besides "typical HGPS," several "atypical progeria"
      syndromes (APS) have been described, in a clinical spectrum ranging from
      mandibuloacral dysplasia to atypical Werner syndrome. These patients's clinical
      features include progeroid manifestations, such as short stature, prominent nose,
      premature graying of hair, partial alopecia, skin atrophy, lipodystrophy,
      skeletal anomalies, such as mandibular hypoplasia and acroosteolyses, and in some
      cases severe atherosclerosis with metabolic complications. APS are due in several
      cases to de novo heterozygous LMNA mutations other than the p.Gly608Gly, or due
      to homozygous BAFN1 mutations in Nestor-Guillermo Progeria syndrome (NGPS). We
      report here and discuss the observation of a non-consanguineous Moroccan patient
      presenting with atypical progeria. The molecular studies showed the heterozygous
      mutation c.412G>A (p.Glu138Lys) of the LMNA gene. This mutation, previously
      reported as a de novo mutation, was inherited from the apparently healthy father
      who showed a somatic cell mosaicism.

PMID- 22991223
TI  - Hearing loss resulting in malpractice litigation: what physicians need to know.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the relationship between hearing loss and
      malpractice litigation. STUDY DESIGN: Retrospective study evaluating state and
      federal civil malpractice litigation pertaining to physician treatment and
      patient hearing loss in the United States during a 10-year period (2001-2011).
      METHODS: A Westlaw search of the computer database Jury Verdicts-All for 2001
      2011 was performed using the search terms "hearing loss" and "malpractice." This
      database includes jury verdicts, judgments, and settlements. RESULTS: Niney-four
      cases were analyzed. There were 53 verdicts favorable for the defense (56%), 28
      verdicts favorable for the plaintiff (30%), and 12 settlements. One case resulted
      in a mistrial. Settlements ranged from $42,500 to $12,500,000, and verdicts
      ranged from $0 to $8,784,000. The average payout for adult plaintiffs was less
      ($549,157) than the payout for minors ($1,349,121). The average payout for a
      surgical case was $579,098, compared to $960,048 for medical etiology of hearing
      loss. Otolaryngologists were the most frequently sued treating physician for
      hearing loss; the second most common defendant was pediatricians (eight cases).
      In the 13 cases in which an otolaryngologist was sued, there were nine defense
      verdicts and four verdicts in plaintiffs' favor. The average indemnity for an
      otolaryngologist was $313,230. CONCLUSIONS: Otolaryngologists are successful in
      most (70%) hearing loss litigation brought against them. This is true regardless
      of whether the allegations are of medical error or include operative procedures.
      Pediatric patients received more favorable jury verdicts when litigating
      malpractice claims than their adult counterparts, and the payouts were highest
      when there was alleged birth trauma and/or meningitis. Finally, the severity and
      degree of hearing loss sustained correlate with higher payouts.

PMID- 22991224
TI  - Complex stiffness gradient substrates for studying mechanotactic cell migration.
AB  - Polyacrylamide gels are cast upon a stiff support with controlled topography,
      resulting in a thin gel layer of variable height. The topographical profiles
      project a stiffness map onto the gel, resulting in controlled linear and non
      linear 2D stiffness gradients. Fibroblasts, which migrate towards stiffer
      substrates, accumulate in areas with a gel thickness below 15 MUm.

PMID- 22991225
TI  - Differentiation capacity of hepatic stem/progenitor cells isolated from D
      galactosamine-treated rat livers.
AB  - Oval cells and small hepatocytes (SHs) are known to be hepatic stem and
      progenitor cells. Although oval cells are believed to differentiate into mature
      hepatocytes (MHs) through SHs, the details of their differentiation process are
      not well understood. Furthermore, it is not certain whether the induced cells
      possess fully mature functions as MHs. In the present experiment, we used Thy1
      and CD44 to isolate oval and progenitor cells, respectively, from D-galactosamine
      treated rat livers. Epidermal growth factor, basic fibroblast growth factor, or
      hepatocyte growth factor could trigger the hepatocytic differentiation of sorted
      Thy1(+) cells to form epithelial cell colonies, and the combination of the
      factors stimulated the emergence and expansion of the colonies. Cells in the
      Thy1(+) -derived colonies grew more slowly than those in the CD44(+) -derived
      ones in vitro and in vivo and the degree of their hepatocytic differentiation
      increased with CD44 expression. Although the induced hepatocytes derived from
      Thy1(+) and CD44(+) cells showed similar morphology to MHs and formed organoids
      from the colonies similar to those from SHs, many hepatic differentiated
      functions of the induced hepatocytes were less well performed than those of
      mature SHs derived from the healthy liver. The gene expression of cytochrome P450
      1A2, tryptophan 2,3-dioxygenase, and carbamoylphosphate synthetase I was lower in
      the induced hepatocytes than in mature SHs. In addition, the protein expression
      of CCAAT/enhancer-binding protein alpha and bile canalicular formation could not
      reach the levels of production of mature SHs. CONCLUSION: The results suggest
      that, although Thy1(+) and CD44(+) cells are able to differentiate into
      hepatocytes, the degree of maturation of the induced hepatocytes may not be equal
      to that of healthy resident hepatocytes. (HEPATOLOGY 2013).

PMID- 22991226
TI  - Histone deacetylase 5 regulates glucose uptake and insulin action in muscle
      cells.
AB  - The class IIa histone deacetylases (HDACs) act as transcriptional repressors by
      altering chromatin structure through histone deacetylation. This family of
      enzymes regulates muscle development and phenotype, through regulation of muscle
      specific genes including myogenin and MyoD (MYOD1). More recently, class IIa
      HDACs have been implicated in regulation of genes involved in glucose metabolism.
      However, the effects of HDAC5 on glucose metabolism and insulin action have not
      been directly assessed. Knockdown of HDAC5 in human primary muscle cells
      increased glucose uptake and was associated with increased GLUT4 (SLC2A4)
      expression and promoter activity but was associated with reduced GLUT1 (SLC2A1)
      expression. There was no change in PGC-1alpha (PPARGC1A) expression. The effects
      of HDAC5 knockdown on glucose metabolism were not due to alterations in the
      initiation of differentiation, as knockdown of HDAC5 after the onset of
      differentiation also resulted in increased glucose uptake and insulin-stimulated
      glycogen synthesis. These data show that inhibition of HDAC5 enhances metabolism
      and insulin action in muscle cells. As these processes in muscle are dysregulated
      in metabolic disease, HDAC inhibition could be an effective therapeutic strategy
      to improve muscle metabolism in these diseases. Therefore, we also examined the
      effects of the pan HDAC inhibitor, Scriptaid, on muscle cell metabolism. In
      myotubes, Scriptaid increased histone 3 acetylation, GLUT4 expression, glucose
      uptake and both oxidative and non-oxidative metabolic flux. Together, these data
      suggest that HDAC5 regulates muscle glucose metabolism and insulin action and
      that HDAC inhibitors can be used to modulate these parameters in muscle cells.

PMID- 22991227
TI  - A new structural model of the acid-labile subunit: pathogenetic mechanisms of
      short stature-causing mutations.
AB  - The acid-labile subunit (ALS) is the main regulator of IGF1 and IGF2
      bioavailability. ALS deficiency caused by mutations in the ALS (IGFALS) gene
      often results in mild short stature in adulthood. Little is known about the ALS
      structure-function relationship. A structural model built in 1999 suggested a
      doughnut shape, which has never been observed in the leucine-rich repeat (LRR)
      superfamily, to which ALS belongs. In this study, we built a new ALS structural
      model, analysed its glycosylation and charge distribution and studied mechanisms
      by which missense mutations affect protein structure. We used three structure
      prediction servers and integrated their results with information derived from ALS
      experimental studies. The ALS model was built at high confidence using Toll-like
      receptor protein templates and resembled a horseshoe with an extensively
      negatively charged concave surface. Enrichment in prolines and disulphide bonds
      was found at the ALS N- and C-termini. Moreover, seven N-glycosylation sites were
      identified and mapped. ALS mutations were predicted to affect protein structure
      by causing loss of hydrophobic interactions (p.Leu134Gln), alteration of the
      amino acid backbone (p.Leu241Pro, p.Leu172Phe and p.Leu244Phe), loss of
      disulphide bridges (p.Cys60Ser and p.Cys540Arg), change in structural constrains
      (p.Pro73Leu), creation of novel glycosylation sites (p.Asp440Asn) or alteration
      of LRRs (p.Asn276Ser). In conclusion, our ALS structural model was identified as
      a highly confident prediction by three independent methods and disagrees with the
      previously published ALS model. The new model allowed us to analyse the ALS core
      and its caps and to interpret the potential structural effects of ALS mutations.

PMID- 22991228
TI  - Therapeutic potential of VIP vs PACAP in diabetes.
AB  - Type 2 diabetes (T2D) is characterized by chronic insulin resistance and a
      progressive decline in beta-cell function. Although rigorous glucose control can
      reduce morbidity and mortality associated with diabetes, achieving optimal long
      term glycemic control remains to be accomplished in many diabetic patients. As
      beta-cell mass and function inevitably decline in T2D, exogenous insulin
      administration is almost unavoidable as a final outcome despite the use of oral
      antihyperglycemic agents in many diabetic patients. Pancreatic islet cell death,
      but not the defect in new islet formation or beta-cell replication, has been
      blamed for the decrease in beta-cell mass observed in T2D patients. Thus,
      therapeutic approaches designed to protect islet cells from apoptosis could
      significantly improve the management of T2D, because of its potential to reverse
      diabetes not just ameliorate glycemia. Therefore, an ideal beta-cell-preserving
      agent is expected to protect beta cells from apoptosis and stimulate postprandial
      insulin secretion along with increasing beta-cell replication and/or islet
      neogenesis. One such potential agent, the islet endocrine neuropeptide vasoactive
      intestinal peptide (VIP) strongly stimulates postprandial insulin secretion.
      Because of its broad spectrum of biological functions such as acting as a potent
      anti-inflammatory factor through suppression of Th1 immune response, and
      induction of immune tolerance via regulatory T cells, VIP has emerged as a
      promising therapeutic agent for the treatment of many autoimmune diseases
      including diabetes.

PMID- 22991229
TI  - Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber
      scaffolds.
AB  - The in vitro generation of a three-dimensional (3-D) myocardial tissue-like
      construct employing cells, biomaterials, and biomolecules is a promising strategy
      in cardiac tissue regeneration, drug testing, and tissue engineering
      applications. Despite significant progress in this field, current cardiac tissue
      models are not yet able to stably maintain functional characteristics of
      cardiomyocytes for long-term culture and therapeutic purposes. The objective of
      this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an
      electrospinning technique and exploring its potential for long-term cardiac
      function in the 3-D co-culture model. Chitosan is a natural polysaccharide
      biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective.
      Electrospun chitosan was utilized to provide structural scaffolding characterized
      by scale and architectural resemblance to the extracellular matrix (ECM) in vivo.
      The chitosan fibers were coated with fibronectin via adsorption in order to
      enhance cellular adhesion to the fibers and migration into the interfibrous
      milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied
      in various culture conditions (i.e., mono- and co-cultures) for their viability
      and function. Cellular morphology and functionality were examined using
      immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction
      protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light
      microscopy were used to investigate cellular morphology, spatial organization,
      and contractions. Calcium indicator was used to monitor calcium ion flux of
      beating cardiomyocytes. The results demonstrate that the chitosan nanofibers
      retained their cylindrical morphology in long-term cell cultures and exhibited
      good cellular attachment and spreading in the presence of adhesion molecule,
      fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte
      polarity and islands of non-coherent contractions. However, the cardiomyocyte
      fibroblast co-cultures resulted in polarized cardiomyocyte morphology and
      retained their morphology and function for long-term culture. The Cx43 expression
      in the fibroblast co-culture was higher than the cardiomyocytes mono-culture and
      endothelial cells co-culture. In addition, fibroblast co-cultures demonstrated
      synchronized contractions involving large tissue-like cellular networks. To our
      knowledge, this is the first attempt to test chitosan nanofiber scaffolds as a 3
      D cardiac co-culture model. Our results demonstrate that chitosan nanofibers can
      serve as a potential scaffold that can retain cardiac structure and function.
      These studies will provide useful information to develop a strategy that allows
      us to generate engineered 3-D cardiac tissue constructs using biocompatible and
      biodegradable chitosan nanofiber scaffolds for many tissue engineering
      applications.

PMID- 22991231
TI  - 18beta-glycyrrhetinic acid inhibits hepatocellular carcinoma development by
      reversing hepatic stellate cell-mediated immunosuppression in mice.
AB  - Hepatic stellate cells (HSCs) have immunosuppressive capabilities and contribute
      to the occurrence and development of hepatocellular carcinoma (HCC). Thus,
      activated HSCs may be a suitable target for HCC therapy. Our study used mixed
      leukocyte reactions (MLR) in vitro to demonstrate that 18beta-glycyrrhetinic acid
      (GA) could reverse HSC-mediated immunosuppression by reducing T-cell apoptosis
      and regulatory T (Treg) cells expression, thereby enhancing the ability of T
      cells to attack tumor cells and attenuating HCC cell invasiveness. Moreover, we
      established a HCC orthotopic implantation model in immunocompetent C57BL/6 mice,
      which suggested that GA played a protective role in HCC development by reducing
      immunosuppression mediated by HSCs in the tumor microenvironment.

PMID- 22991230
TI  - Comparison of two waist circumference measurement protocols: the SEARCH for
      diabetes in youth study.
AB  - BACKGROUND: Reports comparing waist circumference (WC) measurements from young
      populations are scarce. OBJECTIVES: We compared two protocols for measuring waist
      circumference in a sample of youth with diabetes. METHODS: Participants were
      enrolled in the SEARCH for Diabetes in Youth Study (SEARCH). WC was measured at
      least twice by the National Health and Nutrition Examination Survey (NHANES)
      protocol and twice by the World Health Organization (WHO) protocol. Method
      specific averages were used in these analyses. RESULTS: Among 6248 participants,
      the mean NHANES WC (76.3 cm) was greater than the mean WHO WC (71.9 cm).
      Discrepancies between protocols were greater for females than males, among older
      participants, and in those with higher body mass index (BMI). In both sexes and
      four age strata, the WCs using either method were highly correlated with BMI z
      score. The within-method differences between the first and second measurements
      were similar for the two methods. CONCLUSIONS: These analyses do not provide
      evidence that one of these two methods is more reproducible or is a better
      indicator of obesity as defined by BMI z-scores.

PMID- 22991232
TI  - Molecular diagnostics and personalized medicine in oncology: challenges and
      opportunities.
AB  - Increasing evidence demonstrates that target-based agents are active only in
      molecularly selected populations of patients. Therefore, the identification of
      predictive biomarkers has become mandatory to improve the clinical development of
      these novel drugs. Mutations of the epidermal growth factor receptor (EGFR) or
      rearrangements of the ALK gene in non-small-cell lung cancer, and BRAF mutations
      in melanoma are clear examples of driver mutations and predictive biomarkers of
      response to treatment with specific inhibitors. Predictive biomarkers might also
      identify subgroups of patients that are not likely to respond to specific drugs,
      as shown for KRAS mutations and anti-EGFR monoclonal antibodies in colorectal
      carcinoma. The discovery of novel driver molecular alterations and the
      availability of drugs capable to selectively block such oncogenic mechanisms are
      leading to a rapid increase in the number of putative biomarkers that need to be
      assessed in each single patient. In this respect, two different approaches are
      being developed to introduce a comprehensive molecular characterization in
      clinical practice: high throughput genotyping platforms, which allow the
      detection of recognized genetic aberrations in clinical samples, and next
      generation sequencing that can provide information on all the different types of
      cancer-causing alterations. The introduction of these techniques in clinical
      practice will increase the possibility to identify molecular targets in each
      individual patient, and will also allow to follow the molecular evolution of the
      disease during the treatment. By using these approaches, the development of
      personalized medicine for patients with cancer will finally become possible.

PMID- 22991233
TI  - A smart nanofiber web that captures and releases cells.
AB  - Caught in a web: Photo-cross-linkable temperature-responsive polymer-based
      nanofiber webs have been synthesized that have the ability to capture,
      encapsulate, and release cells by dynamically transforming the fibrous structure
      into hydrogel-like structures by wrapping, swelling, and deswelling processes in
      response to external temperature changes (see picture).

PMID- 22991234
TI  - Acute effect of calcium citrate on serum calcium and cardiovascular function.
AB  - Calcium supplements have been associated with an increased risk of cardiovascular
      events. However, the validity of these findings has been questioned. A major
      concern is that the mechanism underlying an increase in cardiovascular events has
      not been demonstrated. Calcium initiates cardiac and vascular contraction
      following influx of calcium into cardiac and smooth muscle from extracellular
      fluid. We have investigated whether the acute rise in serum calcium following
      calcium supplement administration is associated with adverse changes in
      cardiovascular function. In an open interventional study, we recruited 25
      volunteers (16 female, age 60.3 +/- 6.5 years, body mass index 25.7 +/- 2.7
      kg/m2) from the community who were not taking calcium supplements. Participants
      were studied before and 3 hours after a single oral dose of 1000 mg calcium
      citrate. We assessed well-validated markers of arterial stiffness (pulse wave
      velocity [PWV]), arterial wave reflection (augmentation index [AIx]), and
      myocardial perfusion (subendocardial viability ratio [SEVR]) by pulse wave
      analysis and endothelial function (reactive hyperemia index [RHI]) by peripheral
      arterial tonometry. Total and ionized serum calcium were acutely increased by
      0.10 +/- 0.07 and 0.06 +/- 0.03 mmol/L, respectively, 3 hours after calcium
      citrate administration (p < 0.0001 for both comparisons). Following
      administration of calcium citrate there was a fall in AIx from a median of 29.7%
      (23.8% to 34.0%) to 26.4% (22.7% to 34.0%, p = 0.03) and an increase in SEVR from
      163% (148% to 174%) to 170% (149% to 185%, p = 0.007). PWV and RHI were not
      significantly altered. The change in total calcium was negatively correlated with
      the change in AIx (r = -0.48, p = 0.02). In summary, the acute increase in serum
      calcium following calcium supplement administration is associated with reduced
      arterial wave reflection and a marker of increased myocardial perfusion. If
      maintained long-term, these changes would be expected to reduce cardiovascular
      risk. Acute serum calcium-mediated changes in these parameters of cardiovascular
      function are unlikely to underlie an association between calcium supplementation
      and cardiovascular events.

PMID- 22991235
TI  - A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern,
      epilepsy, and permanent neonatal diabetes syndrome (MEDS).
AB  - Wolcott-Rallison syndrome (WRS) and the recently delineated microcephaly with
      simplified gyration, epilepsy, and permanent neonatal diabetes syndrome (MEDS)
      are clinically overlapping autosomal recessive disorders characterized by early
      onset diabetes, skeletal defects, and growth retardation. While liver and renal
      symptoms are more severe in WRS, neurodevelopmental characteristics are more
      pronounced in MEDS patients, in which microcephaly and uncontrolled epilepsy are
      uniformly present. Mutations in the EIF2AK3 gene were described in patients with
      WRS and defects in this gene lead to increased susceptibility to apoptotic cell
      death. Mutations in IER3IP1 have been reported in patients with MEDS and
      similarly, loss of activity results in apoptosis of neurons and pancreatic beta
      cells in patients. Here we report on a homozygous mutation of the IER3IP1 gene in
      four patients from two unrelated consanguineous Egyptian families presenting with
      MEDS who display burst suppression patterns on EEG. All patients presented with
      mildly elevated liver enzymes, microalbuminuria, and skeletal changes such as
      scoliosis and osteopenia, leading to repeated bone fractures. We expand the
      phenotypic spectrum of MEDS caused by IER3IP1 gene mutations and propose that WRS
      and MEDS are overlapping clinical syndromes, displaying significant gene
      dependent clinical variability.

PMID- 22991236
TI  - Accuracy of fine-needle aspiration and imaging in the preoperative workup of
      salivary gland mass lesions treated surgically.
AB  - OBJECTIVES/HYPOTHESIS: Fine-needle aspiration (FNA) biopsy and imaging are
      commonly used in the preoperative assessment of salivary gland mass lesions. The
      goal of this retrospective study was to clarify the role of FNA and imaging in
      the workup of salivary gland masses. STUDY DESIGN: Retrospective cohort study.
      METHODS: A computer search identified patients with an FNA of a salivary gland
      lesion with subsequent excision during a 10-year study period. Chart review of
      study patients was performed, and information on site of lesion, age, gender,
      radiologic diagnosis, pain in the tumor area, and facial paralysis was recorded
      and analyzed. RESULTS: There were 543 patients who had an FNA and subsequent
      histopathology. The majority of the tumors were in the parotid gland (n = 492,
      90.9%), followed by submandibular gland (n = 45, 8.3%). The incidence of
      malignancy across all sites was 29.7%. The mean patient age was 54.1 years, and
      54.1% were female. The sensitivity and specificity of FNA were 85.7% and 99.5%,
      respectively. Positive predictive value (PPV) was 98.6%, and negative predictive
      value (NPV) was 94.3%. A total of 464 patients had available radiologic studies.
      For the radiological diagnoses, sensitivity was 81.8% and specificity was 67.3%,
      whereas PPV and NPV were 52.7% and 89.3%, respectively. CONCLUSIONS: FNA is a
      reliable method of preoperatively assessing both benign and malignant salivary
      gland lesions. Preoperative imaging has a lower sensitivity and specificity than
      FNA in differentiating malignant from benign tumors. Older age, pain, and facial
      paralysis are clinical features independently associated with malignancy.

PMID- 22991237
TI  - Hereditary spastic paraplegia caused by a mutation in the VCP gene.

PMID- 22991238
TI  - Renewing functionalized graphene as electrodes for high-performance
      supercapacitors.
AB  - An acid-assisted ultrarapid thermal strategy is developed for constructing
      specifically functionalized graphene. The electrochemical performance of
      functionalized graphene can be boosted via elaborate coupling between the
      pseudocapacitance and the electronic double layer capacitance through rationally
      tailoring the structure of graphene sheets. This presents an opportunity for
      developing further high-performance graphene-based electrodes to bridge the
      performance gap between traditional capacitors and batteries.

PMID- 22991239
TI  - HINT2 and fatty liver disease: mitochondrial protein hyperacetylation gives a
      hint?

PMID- 22991240
TI  - Flux balance analysis of CHO cells before and after a metabolic switch from
      lactate production to consumption.
AB  - Mammalian cell cultures typically exhibit an energy inefficient phenotype
      characterized by the consumption of large quantities of glucose and the
      concomitant production of large quantities of lactate. Under certain conditions,
      mammalian cells can switch to a more energy efficient state during which lactate
      is consumed. Using a metabolic model derived from a mouse genome scale model we
      performed flux balance analysis of Chinese hamster ovary cells before and after a
      metabolic switch from lactate production (in the presence of glucose) to lactate
      consumption (after glucose depletion). Despite a residual degree of freedom after
      accounting for measurements, the calculated flux ranges and associated errors
      were narrow enough to enable investigation of metabolic changes across the
      metabolic switch. Surprisingly, the fluxes through the lower part of the TCA
      cycle from oxoglutarate to malate were very similar (around 60 umol/gDW/h) for
      both phases. A detailed analysis of the energy metabolism showed that cells
      consuming lactate have an energy efficiency (total ATP produced per total C-mol
      substrate consumed) six times greater than lactate producing cells.

PMID- 22991241
TI  - Leptin predicts a decline in moderate to vigorous physical activity in minority
      female children at risk for obesity.
AB  - What is already known about this subject Physical activity declines as children
      enter puberty. Leptin is cross-sectionally associated with physical activity, but
      there are conflicting findings on the magnitude and direction of this
      association. Leptin concentrations fluctuate during puberty, and may impact
      energy balance. What this study adds Leptin predicts the decline in physical
      activity during the start of puberty independent of central adiposity. Based on a
      median split of leptin, girls with low leptin levels have higher levels of
      physical activity than girls with high leptin levels at the start of puberty.
      Leptin levels at the start of puberty may provide a biological basis for the age
      related physical activity decline in girls. BACKGROUND: Leptin may influence
      moderate to vigorous physical activity (MVPA) at the start of puberty. The
      direction and magnitude of this association are unclear. OBJECTIVES: To determine
      the effect of baseline leptin on MVPA over 1 year in minority girls at high risk
      for obesity. METHODS: Data came from TRANSITIONS, a longitudinal observational
      study on the age-related MVPA decline. Fifty peripubertal girls aged 8-11 years
      at baseline participated. Baseline leptin (ng mL(-1) ) was collected via a
      duplicated assay using a double antibody radio immune assay. MVPA (min d(-1) )
      was measured using accelerometers for at least four 10-h days on a quarterly
      basis for up to 1 year. RESULTS: Continuous leptin was negatively related to MVPA
      (P = 0.001) independent of central adiposity at baseline and predicted the MVPA
      decline over 1 year (P = 0.002). For descriptive purposes, baseline leptin was
      dichotomized at the sample median into 'high leptin' and 'low leptin' categories
      to determine whether MVPA trajectories differed between these groups. Girls with
      'low leptin' at baseline had significantly higher levels of MPVA at baseline,
      visit 1 and visit 2 compared to girls with 'high leptin'. CONCLUSIONS: High
      leptin levels predicted nearly a 12.6% decline in MVPA over 1 year. These
      findings provide support for the biological basis of declining MVPA as girls
      enter puberty.

PMID- 22991242
TI  - Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is characterized by progressive beta-cell
      dysfunctioning and insulin resistance. This article reviews recent literature
      with special focus on inflammatory mechanisms that provoke the pathogenesis of
      T2DM. We have focused on the recent advances in progression of T2DM including
      various inflammatory mechanisms that might induce inflammation, insulin
      resistance, decrease insulin secretion from pancreatic islets and dysfunctioning
      of beta-cells. Here we have also summarized the role of various pro-inflammatory
      mediators involved in inflammatory mechanisms, which may further alter the normal
      structure of beta-cells by inducing pancreatic islet's apoptosis. In conclusion,
      it is suggested that the role of inflammation in pathogenesis of T2DM is crucial
      and cannot be neglected. Moreover, the insight of inflammatory responses in T2DM
      may provide a new gateway for the better treatment of diabetes mellitus.

PMID- 22991243
TI  - Authors' reply to comments on a recent meta-analysis: Obesity and lung cancer.

PMID- 22991244
TI  - Cyclization of peptides by using selenolanthionine bridges.

PMID- 22991245
TI  - Opposing phenotypes in mice with Smith-Magenis deletion and Potocki-Lupski
      duplication syndromes suggest gene dosage effects on fluid consumption behavior.
AB  - A quantitative long-term fluid consumption and fluid-licking assay was performed
      in two mouse models with either an ~2 Mb genomic deletion, Df(11)17, or the
      reciprocal duplication copy number variation (CNV), Dp(11)17, analogous to the
      human genomic rearrangements causing either Smith-Magenis syndrome [SMS; OMIM
      #182290] or Potocki-Lupski syndrome [PTLS; OMIM #610883], respectively. Both
      mouse strains display distinct quantitative alterations in fluid consumption
      compared to their wild-type littermates; several of these changes are
      diametrically opposing between the two chromosome engineered mouse models. Mice
      with duplication versus deletion showed longer versus shorter intervals between
      visits to the waterspout, generated more versus less licks per visit and had
      higher versus lower variability in the number of licks per lick-burst as compared
      to their respective wild-type littermates. These findings suggest that copy
      number variation can affect long-term fluid consumption behavior in mice. Other
      behavioral differences were unique for either the duplication or deletion
      mutants; the deletion CNV resulted in increased variability of the licking
      rhythm, and the duplication CNV resulted in a significant slowing of the licking
      rhythm. Our findings document a readily quantitated complex behavioral response
      that can be directly and reciprocally influenced by a gene dosage effect.

PMID- 22991246
TI  - Meta-analysis of vertebral augmentation compared with conservative treatment for
      osteoporotic spinal fractures.
AB  - Cement augmentation is a controversial treatment for painful vertebral
      compression fractures (VCF). Our research questions for the meta-analysis were:
      Is there a clinical and statistical difference in pain relief, functional
      improvement, and quality of life between conservative care and cement
      augmentation for VCF and, if so, are they maintained at longer time points? We
      conducted a search of MEDLINE from January 1980 to July 2011 using PubMed,
      Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and
      EMBASE. Searches were performed from medical subject headings. Terms
      "vertebroplasty" and "compression fracture" were used. The outcome variables of
      pain, functional measures, health-related quality of life (HRQOL), and new
      fracture risk were analyzed. A random effects model was chosen. Continuous
      variables were calculated using the standardized mean difference comparing
      improvement from baseline of the experimental group with the control group. New
      vertebral fracture risk was calculated using log odds ratio. Six studies met the
      criteria. The pain visual analog scale (VAS) mean difference was 0.73 (confidence
      interval [CI] 0.35, 1.10) for early (<12 weeks) and 0.58 (CI 0.19, 0.97) for late
      time points (6 to 12 months), favoring vertebroplasty (p < 0.001). The functional
      outcomes at early and late time points were statistically significant with 1.08
      (CI 0.33, 1.82) and 1.16 (CI 0.14, 2.18), respectively. The HRQOL showed superior
      results of vertebroplasty compared with conservative care at early and late time
      points of 0.39 (CI 0.16, 0.62) and 0.33 (CI 0.16, 0.51), respectively. Secondary
      fractures were not statistically different between the groups, 0.065 (CI -0.57,
      0.70). This meta-analysis showed greater pain relief, functional recovery, and
      health-related quality of life with cement augmentation compared with controls.
      Cement augmentation results were significant in the early (<12 weeks) and the
      late time points (6 to 12 months). This meta-analysis provides strong evidence in
      favor of cement augmentation in the treatment of symptomatic VCF fractures.

PMID- 22991248
TI  - From binary to ternary solvent: morphology fine-tuning of D/A blends in PDPP3T
      based polymer solar cells.
AB  - For the PDPP3T/PCBM system investigated here, atomic force microscopy, resonant
      soft X-ray scattering, and grazing incidence wide angle X-ray scattering are used
      as an initial set of tools to determine the surface texture, the bulk
      compositional morphology, and the crystallization behavior, respectively. We find
      systematic variations and relate them to device performance. A solvent mixture of
      DCB/CF/DIO = 76:19:5 (v/v/v) yields a PCE of 6.71%.

PMID- 22991249
TI  - Is the Sino-Nasal Outcome Test-22 a suitable evaluation for septorhinoplasty?
AB  - OBJECTIVES/HYPOTHESIS: It is becoming increasingly important for clinicians to
      demonstrate the impact of their interventions. The Sino-Nasal Outcome Test-22
      (SNOT-22) questionnaire is a disease-specific questionnaire involving 22 symptoms
      combining rhinologic issues with general health issues. We evaluated the SNOT-22
      score as a quality-of-life outcome measure in septorhinoplasty surgery. STUDY
      DESIGN: Outcome research. METHODS: We carried out a prospective case series in 76
      patients undergoing septorhinoplasty. Their SNOT-22 scores were compared pre- and
      postoperatively. We also recorded individual symptom scores to study the impact
      of surgery. To check its reliability, the SNOT-22 score was correlated to patient
      reported symptoms on a visual analogue scale. Patients were screened for comorbid
      conditions. Interactions with the surgical technique and/or with the initial
      sinonasal disease were sought. RESULTS: The SNOT-22 is a reliable and responsive
      outcome measure in septorhinoplasty surgery. Septorhinoplasty was especially
      effective at addressing nasal obstruction, discharge, olfaction, related sleep
      disturbance, and emotional symptoms such as embarrassment or frustration.
      Comparison to the visual analogue scale instrument confirmed the outcome measured
      by the SNOT-22. CONCLUSIONS: The SNOT-22 could be used in routine clinical
      practice to highlight the impact of nasal disease in each patient and to measure
      the outcome and the effectiveness of the surgical intervention.

PMID- 22991247
TI  - Intestinal mucus-derived nanoparticle-mediated activation of Wnt/beta-catenin
      signaling plays a role in induction of liver natural killer T cell anergy in
      mice.
AB  - The Wnt/beta-catenin pathway has been known to play a role in induction of immune
      tolerance, but its role in the induction and maintenance of natural killer T
      (NKT) cell anergy is unknown. We found that activation of the Wnt pathways in the
      liver microenvironment is important for induction of NKT cell anergy. We
      identified a number of stimuli triggering Wnt/beta-catenin pathway activation,
      including exogenous NKT cell activator, glycolipid alpha-GalCer, and endogenous
      prostaglandin E2 (PGE2). Glycolipid alpha-GalCer treatment of mice induced the
      expression of wnt3a and wnt5a in the liver and subsequently resulted in a liver
      microenvironment that induced NKT cell anergy to alpha-GalCer restimulation. We
      also found that circulating PGE2 carried by nanoparticles is stable, and that
      these nanoparticles are A33(+) . A33(+) is a marker of intestinal epithelial
      cells, which suggests that the nanoparticles are derived from the intestine. Mice
      treated with PGE2 associated with intestinal mucus-derived exosome-like
      nanoparticles (IDENs) induced NKT cell anergy. PGE2 treatment leads to activation
      of the Wnt/beta-catenin pathway by inactivation of glycogen synthase kinase 3beta
      of NKT cells. IDEN-associated PGE2 also induces NKT cell anergy through
      modification of the ability of dendritic cells to induce interleukin-12 and
      interferon-beta in the context of both glycolipid presentation and Toll-like
      receptor-mediated pathways. CONCLUSION: These findings demonstrate that IDEN
      associated PGE2 serves as an endogenous immune modulator between the liver and
      intestines and maintains liver NKT cell homeostasis. This finding has
      implications for development of NKT cell-based immunotherapies. (HEPATOLOGY
      2013).

PMID- 22991250
TI  - Early retinol-binding protein levels are associated with growth changes in
      infants born to diabetic mothers.
AB  - BACKGROUND: Biochemical predictors of infants' growth changes are not available.
      OBJECTIVES: We tested whether retinol-binding protein (RBP), docosahexaenoic acid
      and insulin (I) measured within 72 h from birth are associated with growth
      changes in infants born to mothers with gestational diabetes mellitus (GDM).
      METHODS: Fifty-six children, 32 born to diabetic mothers treated with insulin
      (GDM-I) and 24 born to diabetic mothers treated with diet (GDM-D), were evaluated
      at 0, 1, 3, 6 and 12 months of life. RESULTS: At multivariable regression
      performed using generalized estimating equations, early RBP levels and maternal
      body mass index were associated to average weight changes and early RBP and
      insulin levels to average length changes, respectively. There was no difference
      between GDM-I and GDM-D infants. CONCLUSIONS: This exploratory study suggests
      that early RBP levels may be a predictor of growth changes.

PMID- 22991251
TI  - Comments on a recent meta-analysis: Obesity and lung cancer.

PMID- 22991253
TI  - Characterization of Epstein-Barr virus reactivation in a modeled spaceflight
      system.
AB  - Epstein-Barr virus (EBV) is the causative agent of mononucleosis and is also
      associated with several malignancies, including Burkitt's lymphoma, Hodgkin's
      lymphoma, and nasopharyngeal carcinoma, among others. EBV reactivates during
      spaceflight, with EBV shedding in saliva increasing to levels ten times those
      observed pre-and post-flight. Although stress has been shown to increase
      reactivation of EBV, other factors such as radiation and microgravity have been
      hypothesized to contribute to reactivation in space. We used a modeled
      spaceflight environment to evaluate the influence of radiation and microgravity
      on EBV reactivation. BJAB (EBV-negative) and Raji (EBV-positive) cell lines were
      assessed for viability/apoptosis, viral antigen and reactive oxygen species
      expression, and DNA damage and repair. EBV-infected cells did not experience
      decreased viability and increased apoptosis due to modeled spaceflight, whereas
      an EBV-negative cell line did, suggesting that EBV infection provided protection
      against apoptosis and cell death. Radiation was the major contributor to EBV
      ZEBRA upregulation. Combining modeled microgravity and radiation increased DNA
      damage and reactive oxygen species while modeled microgravity alone decreased DNA
      repair in Raji cells. Additionally, EBV-infected cells had increased DNA damage
      compared to EBV-negative cells. Since EBV-infected cells do not undergo apoptosis
      as readily as uninfected cells, it is possible that virus-infected cells in EBV
      seropositive individuals may have an increased risk to accumulate DNA damage
      during spaceflight. More studies are warranted to investigate this possibility.

PMID- 22991252
TI  - A phase 2 trial of induction nab-paclitaxel and cetuximab given with cisplatin
      and 5-fluorouracil followed by concurrent cisplatin and radiation for locally
      advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Complete response (CR) at the primary tumor site as assessed by
      clinical examination following induction chemotherapy with PF (cisplatin and 5
      fluorouracil [5-FU]) is a favorable predictive factor for overall survival and
      disease control in patients with locally advanced squamous cell carcinoma of the
      head and neck. In most series, the rate of CR at the primary site after induction
      PF was 20% to 30%. This study evaluated the efficacy and feasibility of induction
      nab-paclitaxel and cetuximab given with PF (ACPF) followed by definitive
      chemoradiation (CRT) in a phase 2 trial. METHODS: Patients with squamous cell
      carcinoma of the head and neck were treated with ACPF (nab-paclitaxel 100 mg/m(2)
      /week; cetuximab 250 mg/m(2) /week; cisplatin 75 mg/m(2) on day 1; 5-FU 750
      mg/m(2) /day on days 1 through 3) every 21 days for 3 cycles followed by CRT
      (cisplatin 100 mg/m(2) on days 1, 22, and 43 of radiation therapy [RT]). CR at
      the primary tumor site after 2 cycles of ACPF was the primary endpoint. RESULTS:
      Thirty patients were enrolled, of which 22 (73%) had large (T3/T4) primary
      tumors. The CR rate at the primary tumor site after 2 cycles of ACPF was 53% and
      the overall response rate was 100%. Twenty-nine (96%) patients completed 3 cycles
      of ACPF, 26 (90%) completed definitive RT per protocol, and 22 of the 27
      evaluable patients (81%) received > 2 of the 3 planned doses of cisplatin with
      RT. The estimated 2-year overall and progression-free survival rates were 84% and
      65%, respectively. CONCLUSIONS: Induction ACPF resulted in a high CR rate (53%)
      at the primary tumor site even in large tumors and did not adversely affect
      delivery of definitive CRT. Further investigation of ACPF is warranted.

PMID- 22991254
TI  - Genuine redox isomerism in a rare-earth-metal complex.
AB  - Redox isomerism is observed for a lanthanide complex for the first time. Upon
      lowering the temperature, an electron of [{(dpp-bian)Yb(MU-Cl)(dme)}(2)] (1) is
      transferred from the metal to the ligand (see picture), giving rise to marked
      shortening of Yb-N bonds and a hysteretic jump in the magnetic moment. The
      crystal packing is of a crucial importance, as two other crystal modifications of
      1 do not undergo this effect.

PMID- 22991255
TI  - Insertional translocation of 15q25-q26 into 11p13 and duplication at 8p23.1
      characterized by high resolution arrays in a boy with congenital malformations
      and aniridia.
AB  - We report on a boy presenting submucous cleft palate, hydronephrosis,
      ventriculoseptal defect, aniridia, and developmental delay. Additional material
      on 11p13 was cytogenetically visible and array analyses identified a duplicated
      segment on 15q25-26 chromosome region; further, array analyses revealed a small
      deletion (49 kb) at 11p13 region involving the ELP4 gene and a duplication at
      8p23.1. Results were confirmed with both molecular and molecular cytogenetics
      techniques. Possibilities for etiological basis of clinical phenotype are
      discussed.

PMID- 22991256
TI  - Increased cortical porosity in type 2 diabetic postmenopausal women with
      fragility fractures.
AB  - The primary goal of this study was to assess peripheral bone microarchitecture
      and strength in postmenopausal women with type 2 diabetes with fragility
      fractures (DMFx) and to compare them with postmenopausal women with type 2
      diabetics without fractures (DM). Secondary goals were to assess differences in
      nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic
      postmenopausal women without fragility fractures (Co), and in DM and Co women.
      Eighty women (mean age 61.3 +/- 5.7 years) were recruited into these four groups
      (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual-energy X
      ray absorptiometry (DXA) and high-resolution peripheral quantitative computed
      tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR
      pQCT images volumetric bone mineral density and cortical and trabecular structure
      measures, including cortical porosity, were calculated. Bone strength was
      estimated using micro-finite element analysis (uFEA). Differential strength
      estimates were obtained with and without open cortical pores. At the ultradistal
      and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009;
      +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and
      endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the
      distal radius DMFx had 4.7-fold greater relative porosity (p < 0.0001) than DM.
      At the ultradistal radius, intracortical pore volume was significantly higher in
      DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular
      heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and
      cortical BMD (ultradistal tibia: -12.6%, p = 0.031; -6.8%, p = 0.011) than DM.
      DMFx exhibited significantly higher pore-related deficits in stiffness, failure
      load, and cortical load fraction at the ultradistal and distal tibia, and the
      distal radius than DM. Comparing nondiabetic Fx and Co, we only found a
      nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the
      ultradistal radius. The results of our study suggest that severe deficits in
      cortical bone quality are responsible for fragility fractures in postmenopausal
      diabetic women.

PMID- 22991257
TI  - Effect of type 2 diabetes on risk for malignancies includes hepatocellular
      carcinoma in chronic hepatitis C.
AB  - The aim of this retrospective cohort study was to assess the cumulative
      development incidence and predictive factors for malignancies after the
      termination of interferon (IFN) therapy in Japanese patients for hepatitis C
      virus (HCV). A total of 4,302 HCV-positive patients treated with IFN were
      enrolled. The mean observation period was 8.1 years. The primary outcome was the
      first onset of malignancies. Evaluation was performed using the Kaplan-Meier
      method and Cox proportional hazard analysis. A total of 606 patients developed
      malignancies: 393 developed hepatocellular carcinoma (HCC) and 213 developed
      malignancies other than HCC. The cumulative development rate of HCC was 4.3% at 5
      years, 10.5% at 10 years, and 19.7% at 15 years. HCC occurred significantly
      (P<0.05) when the following characteristics were present: advanced histological
      staging, sustained virological response not achieved, male sex, advanced age of
      >=50 years, total alcohol intake of >=200 kg, and presence of type 2 diabetes
      (T2DM). T2DM caused a 1.73-fold enhancement in HCC development. In patients with
      T2DM, HCC decreased when patients had a mean hemoglobin A1c (HbA1c) level of
      <7.0% during follow-up (hazard ratio, 0.56; 95% confidence interval, 0.33-0.89;
      P=0.015). The cumulative development rate of malignancy other than HCC was 2.4%
      at 5 years, 5.1% at 10 years, and 9.8% at 15 years. Malignancies other than HCC
      occurred significantly when patients were of advanced age of <=50 years, smoking
      index (package per day*year) was >=20, and T2DM was present. T2DM caused a 1.70
      fold enhancement in the development of malignancies other than HCC. CONCLUSION:
      T2DM causes an approximately 1.7-fold enhancement in the development of HCC and
      malignancies other than HCC in HCV-positive patients treated with IFN. In T2DM
      patients, maintaining a mean HbA1c level of <7.0% reduces the development of HCC.

PMID- 22991259
TI  - Metal amidoboranes: superior double-hydrogen-transfer agents in the reduction of
      ketones and imines.
AB  - Metal amidoboranes (MABs), such as lithium amidoborane (LiAB), show superior
      ability in reducing ketones and imines directly into their corresponding
      secondary alcohols and amines, respectively, at room temperature with high
      conversion and yields. A mechanistic study indicates that the reduction proceeds
      through a double-hydrogen-transfer process. Both protic H(N) and hydridic H(B)
      protons in the amidoborane participate in the reaction. Theoretical
      investigations show that the first (and rate-determining) step of the reduction
      reaction is the elimination of LiH from LiAB, followed by the transfer of H(Li)
      to the C site of the unsaturated bond.

PMID- 22991258
TI  - Diagnostic significance of narrow-band imaging for detecting high-grade
      dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the diagnostic accuracy of the established
      patterns of intraepithelial microvasculature of narrow-band imaging (NBI) in
      diagnosing upper aerodigestive tract neoplasm of the squamous epithelium for
      detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral
      leukoplakia. STUDY DESIGN: Retrospective case-control study. METHODS: Using
      histopathological findings as the standard, clinical diagnosis of oral
      leukoplakia and 3 different but established NBI criteria were compared and
      evaluated statistically. RESULTS: A total of 414 patients, including 365 males
      and 49 females, with mean age of 52.15 +/- 10.75 years, were enrolled. The odds
      ratio of detecting high-grade dysplasia and carcinomatous lesions by twisted
      elongation of intraepithelial papillary capillary loop (IPCL) and IPCL pattern
      destruction was 95.53 (confidence interval 95%: 42.19-216.29), and the
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy were 84.62%, 94.56%, 74.32%, 97.06%, and 93.0%, respectively, which
      were significantly better than the other two established NBI criteria (p <
      0.001). CONCLUSIONS: The NBI images of twisted elongation of IPCL and IPCL
      pattern destruction are indicators of high-grade dysplasia or carcinomatous
      lesions in oral leukoplakia.

PMID- 22991260
TI  - N-terminal prohormone of brain natriuretic peptide: a useful tool for the
      detection of acute pulmonary artery embolism in post-surgical patients.
AB  - BACKGROUND: Acute pulmonary embolism (APE) is an important clinical problem in
      patients after major surgery and often remains a difficult diagnosis because of
      unspecific clinical symptoms. Therefore, we investigated the role of N-terminal
      prohormone of brain natriuretic peptide (NT-proBNP) for the detection of APE.
      METHODS: In 44 patients with suspected APE referred to the intensive care unit
      after major surgery, serum NT-proBNP, troponin-I, and D-dimers were measured
      according to the standard hospital protocol. To definitively confirm or exclude
      APE, all patients underwent an angiographic CT scan of the thorax. RESULTS: APE
      was confirmed in 28 and excluded in 16 patients by CT scan. NT-proBNP was
      significantly (P<0.01) higher in patients with APE [4425 (sd 8826; range 63-35
      000) pg ml(-1)] compared with those without [283 (sd 327; range 13-1133) pg ml(
      1)]. The sensitivity of the NT-proBNP screening was 93%, specificity 63%,
      positive predictive value 81%, and negative predictive value 83%. There were no
      significant (P = 0.96) differences in D-dimers between subjects with and without
      APE [confirmed APE: 511 (sd 207; range 83-750) MUg litre(-1); excluded APE: 509
      (sd 170; range 230-750) MUg litre(-1)]. Troponin-I levels were not elevated in
      32% of the patients with APE. CONCLUSIONS: D-dimer levels are frequently elevated
      in post-surgical patients and not applicable for confirmation or exclusion of
      APE. In contrast, NT-proBNP appears to be a useful biomarker for APE diagnosis in
      the postoperative setting. In the case of NT-proBNP levels below the upper
      reference limit, haemodynamically relevant APE is unlikely. Troponin-I in
      contrast is not considered to be helpful.

PMID- 22991261
TI  - Role of the Internet as an information resource for surgical patients: a survey
      of 877 patients.
AB  - BACKGROUND: This study was conducted to provide preliminary data regarding
      current Internet use practices for information about anaesthesia in patients
      undergoing elective surgical procedures at a major academic institution. METHODS:
      With IRB approval, 2936 patients coming for preanaesthetic evaluation at a
      tertiary academic hospital's preadmission testing (PAT) centre were invited to
      voluntarily participate in a 20-item questionnaire designed to obtain
      participants' characteristics and Internet use for information pertaining to
      their upcoming surgery. Data were analysed using statistical software SAS (Cary,
      NC, USA). Descriptive statistics were calculated for continuous variables using
      mean (sd), and for categorical data using n (%). Association analysis was
      performed using the Fisher's exact test. RESULTS: Eight hundred and seventy-seven
      patients (30%) responded. Of these, 356 (41%) looked for information about their
      medical condition, 321 (37%) for their surgery, 279 (32%) for surgeon, 163 (19%)
      for the hospital, and only 36 (4%) for information regarding anaesthesia. Of
      these 36 patients, 14 (39%) said the sites they used helped answer their
      questions regarding anaesthesia. Of the 831 patients who did not use the Internet
      for anaesthesia, 503 (57%) indicated that they would be receptive to being
      directed to specific websites for anaesthesia. CONCLUSIONS: Of the patients
      coming for elective surgery who responded (30%), the majority did not use the
      Internet to seek information regarding anaesthesia. Respondents indicated a high
      degree of interest in being directed to appropriate websites for further
      information. These results suggest that it may be beneficial to include
      information regarding reliable web-based resources to interested patients at
      preoperative visits.

PMID- 22991262
TI  - Increased Toll-like receptor (TLR) mRNA expression in monocytes is a feature of
      metabolic syndrome in adolescents.
AB  - BACKGROUND: Metabolic syndrome (MetSyn) is diagnosed frequently in some but not
      all overweight adolescents. Chronic inflammation, as seen in obesity, is strongly
      associated with MetSyn. OBJECTIVES: The aim of this pilot study was to assess the
      correlation between activation of the innate immune system and MetSyn,
      independent of body mass index (BMI), in a young population. METHODS: We
      quantitatively measured both systemic pro-inflammatory cytokines and gene
      expression of Toll-like receptors (TLRs) and downstream cytokines in circulating
      monocytes obtained from nine adolescents with metabolic syndrome (Overwt-MetSyn)
      and eight BMI-matched controls (Overwt-Healthy). RESULTS: The Overwt-MetSyn group
      demonstrated a significant elevation in expression of TLR2, TLR4, tumour necrosis
      factor-a (TNF a) and interleukin-6 (IL6) in peripheral monocytes, and increased
      circulating levels of TNF a and IL6 when compared with the Overwt-Healthy group.
      TLR2 (r = 0.78, P < 0.001), TLR4 (r = 0.57, P < 0.01) and TNF a (r = 0.61, P <
      0.01) gene expression positively correlated with serum levels of TNF a.
      CONCLUSIONS: Our study suggests that activation of the innate immune pathway via
      TLRs may be partially responsible for the increased systemic inflammation seen in
      adolescents with MetSyn.

PMID- 22991263
TI  - Laparoscopic pancreatectomy for malignancy.
AB  - Utilization of laparoscopic techniques for resection of the pancreas has slowly
      gained acceptance in specific situations and is now being applied to more
      challenging endeavors, such as pancreaticoduodenectomy for cancer. This review
      provides a summary of laparoscopic applications for pancreatic malignancy, with
      specific attention to the most common methods of pancreatic resection and their
      respective oncologic outcomes, including margin status, lymph node retrieval, and
      survival.

PMID- 22991265
TI  - Kinetic resolution of nitrogen heterocycles with a reusable polymer-supported
      reagent.
AB  - Shake it up baby! Simply shaking a polymer-supported reagent and the racemic
      amine at room temperature kinetically resolves a broad range of N-heterocycles
      with good selectivity. The polymer-supported reagents are robust, easy to
      regenerate, and can be reused dozens of times. Cleavable acyl groups can be used
      to give access to both amine enantiomers in a single resolution.

PMID- 22991264
TI  - Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic
      thyroid carcinoma in vitro and in vivo.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is a very aggressive thyroid gland
      malignancy with very poor prognosis. It is suspected that the Notch signaling
      pathway, which is not active in ATC, may have a tumor suppressor function in this
      neoplasm. However, it remains unknown whether activation of Notch can yield
      therapeutic efficacies in ATC. METHODS: The purpose of this study was to evaluate
      the effect of chrysin, a potential Notch inducer identified via high-throughput
      screening, on ATC both in vitro and in vivo. RESULTS: Chrysin treatment of ATC
      cells led to a dose-dependent inhibition of cellular growth. Protein and
      messenger RNA levels of Notch1 and Hes1 (hairy/enhancer of split 1), a downstream
      Notch1 effector, were both up-regulated with treatment. Luciferase reporter
      assays incorporating the C promoter-binding factor 1 (CBF1) binding site also
      confirmed the functional activity of chrysin-induced Notch1. Oral administration
      of chrysin suppressed the growth of ATC xenografts by an average of 59% compared
      with the vehicle control group (P = .002). In addition, calculated median time to
      tumor progression was 11 days for control mice and 21 days for the chrysin
      treatment group (P = .008). Analysis of chrysin-treated ATC tumors revealed an
      increase in the active intracellular domain of Notch1 protein. Activation of
      Notch1 in vivo was associated with the induction of cleaved Poly ADP ribose
      polymerase (PARP) protein, indicating that the growth inhibition was due to
      apoptosis. CONCLUSIONS: The novel Notch1 activator chrysin inhibits tumor growth
      in ATC both in vitro and in vivo. Chrysin could be a promising therapeutic
      candidate for ATC, and this justifies further clinical studies.

PMID- 22991266
TI  - Brain arteriovenous malformations associated with hereditary hemorrhagic
      telangiectasia: gene-phenotype correlations.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic
      disease with a wide spectrum of vascular malformations (VMs) involving multiple
      organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations
      (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study
      clinical manifestations of brain AVMs in patients with HHT and correlate these
      with the specific gene mutated. We reviewed records of 171 patients with HHT and
      brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age
      of 26 +/- 18 range, (0-68) years. All of patients with ICH were neurologically
      asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of
      patients on initial examination. Genetic test results were available in 109 (64%)
      patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%),
      and 2 (2%), respectively. A history of ICH was reported in 24% of patients with
      an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of
      26 +/- 16 (range, 2-50) and 18 +/- 21 (0-48) years, respectively. No
      statistically significant differences in age at first brain AVM diagnosis,
      prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were
      observed among gene groups. In conclusion, no evidence for differences in brain
      AVM characteristics was observed among HHT gene groups, although we cannot
      exclude clinically important differences. Larger studies are needed to further
      guide brain AVM screening decisions in patients with HHT.

PMID- 22991267
TI  - Potassium citrate supplementation results in sustained improvement in calcium
      balance in older men and women.
AB  - The dietary acid load created by the typical Western diet may adversely impact
      the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid
      with alkaline potassium salts results in sustained improvements in calcium
      balance remains controversial. In this randomized, double-blind, placebo
      controlled study, 52 men and women (mean age 65.2 +/- 6.2 years) were randomly
      assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with
      measurements of bone turnover markers, net acid excretion, and calcium
      metabolism, including intestinal fractional calcium absorption and calcium
      balance, obtained at baseline and at 6 months. At 6 months, net acid excretion
      was significantly lower in both treatment groups compared to placebo and it was
      negative, meaning subjects' dietary acid was completely neutralized (-11.3 mmol/d
      on 60 mmol/d; -29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6
      months, 24-hour urine calcium was significantly reduced in persons taking
      potassium citrate 60 mmol/d (-46 +/- 15.9 mg/d) and 90 mmol/d (-59 +/- 31.6 mg/d)
      compared with placebo (p < 0.01). Fractional calcium absorption was not changed
      by potassium citrate supplementation. Net calcium balance was significantly
      improved in participants taking potassium citrate 90 mmol/d compared to placebo
      (142 +/- 80 mg/d on 90 mmol/d versus -80 +/- 54 mg/d on placebo; p = 0.02).
      Calcium balance was also improved on potassium citrate 60 mmol/d, but this did
      not reach statistical significance (p = 0.18). Serum C-telopeptide decreased
      significantly in both potassium citrate groups compared to placebo (-34.6 +/-
      39.1 ng/L on 90 mmol/d, p = 0.05; -71.6 +/- 40.7 ng/L on 60 mmol/d, p = 0.02)
      whereas bone-specific alkaline phosphatase did not change. Intact parathyroid
      hormone was significantly decreased in the 90 mmol/d group (p = 0.01). Readily
      available, safe, and easily administered in an oral form, potassium citrate has
      the potential to improve skeletal health. Longer-term trials with definitive
      outcomes such as bone density and fracture are needed.

PMID- 22991268
TI  - Subunit organization of a synechocystis hetero-oligomeric thylakoid FtsH complex
      involved in photosystem II repair.
AB  - FtsH metalloproteases are key components of the photosystem II (PSII) repair
      cycle, which operates to maintain photosynthetic activity in the light. Despite
      their physiological importance, the structure and subunit composition of
      thylakoid FtsH complexes remain uncertain. Mutagenesis has previously revealed
      that the four FtsH homologs encoded by the cyanobacterium Synechocystis sp PCC
      6803 are functionally different: FtsH1 and FtsH3 are required for cell viability,
      whereas FtsH2 and FtsH4 are dispensable. To gain insights into FtsH2, which is
      involved in selective D1 protein degradation during PSII repair, we used a strain
      of Synechocystis 6803 expressing a glutathione S-transferase (GST)-tagged
      derivative (FtsH2-GST) to isolate FtsH2-containing complexes. Biochemical
      analysis revealed that FtsH2-GST forms a hetero-oligomeric complex with FtsH3.
      FtsH2 also interacts with FtsH3 in the wild-type strain, and a mutant depleted in
      FtsH3, like ftsH2(-) mutants, displays impaired D1 degradation. FtsH3 also forms
      a separate heterocomplex with FtsH1, thus explaining why FtsH3 is more important
      than FtsH2 for cell viability. We investigated the structure of the isolated
      FtsH2-GST/FtsH3 complex using transmission electron microscopy and single
      particle analysis. The three-dimensional structural model obtained at a
      resolution of 26 A revealed that the complex is hexameric and consists of
      alternating FtsH2/FtsH3 subunits.

PMID- 22991269
TI  - Investigations on non-inferiority--the Food and Drug Administration draft
      guidance on treatments for nosocomial pneumonia as a case for exact tests for
      binomial proportions.
AB  - This paper addresses statistical issues in non-inferiority trials where the
      primary outcome is a fatal event. The investigations are inspired by a recent
      Food and Drug Administration (FDA) draft guideline on treatments for nosocomial
      pneumonia. The non-inferiority margin suggested in this guideline for the
      endpoint all-cause mortality is defined on different distance measures (rate
      difference and odds ratio) and is discontinuous. Furthermore, the margin enables
      considerable power for the statistical proof of non-inferiority at alternatives
      that might be regarded as clinically unacceptable, that is, even if the
      experimental treatment is harmful as compared with the control. We investigated
      the appropriateness of the proposed non-inferiority margin as well as the
      performance of possible test statistics to be used for the analysis. A continuous
      variant of the margin proposed in the FDA guideline together with the
      unconditional exact test according to Barnard showed favorable characteristics
      with respect to type I error rate control and power. To prevent harmful new
      treatments from being declared as non-inferior, we propose to add a 'second
      hurdle'. We discuss examples and explore power characteristics when requiring
      both statistical significance and overcoming the second hurdle.

PMID- 22991270
TI  - Is NIH funding predictive of greater research productivity and impact among
      academic otolaryngologists?
AB  - OBJECTIVES/HYPOTHESIS: The h-index is an accurate and reliable indicator of
      scholarly productivity that takes into account relevance, significance, and
      influence of research contributions. As such, it is an effective, objective
      bibliometric that can be used to evaluate academic otolaryngologists for
      decisions regarding appointment and advancement. In this study, we evaluate the
      impact of NIH funding on scholarly productivity in otolaryngology. STUDY DESIGN:
      Analysis of bibliometric data of academic otolaryngologists. METHODS: Funding
      data for the 20 otolaryngology departments with the largest aggregate total of
      NIH grants for the fiscal years (FY) 2011 and 2012 was obtained using the
      National Institutes of Health Research Portfolio Online Reporting Tools
      Expenditures and Reports (RePORTER) Database. H-indices were calculated using the
      Scopus online database, and then compared to funding data at both the
      departmental and individual level. RESULTS: Faculty members in otolaryngology
      departments who received NIH funding had significantly greater research
      productivity and impact, as measured by the h-index, than their nonfunded peers.
      H-indices increased with greater NIH funding levels, and investigators with MD
      degrees tended to have higher mean NIH funding levels than those with PhDs. While
      there was no correlation between average h-index and NIH funding totals at the
      level of departments, there was greater correlation upon examination of NIH
      funding levels of individual investigators. CONCLUSIONS: The h-index has a strong
      relationship with, and may be predictive of, grant awards of NIH-funded faculty
      members in otolaryngology departments. This bibliometric may be useful in
      decisions regarding appointment and advancement of faculty members within
      academic otolaryngology departments.

PMID- 22991271
TI  - A spectroscopic and computational study of a photoinduced cross-dehydrogenative
      coupling reaction of a stable semiquinone radical.
AB  - Norrish-type-II reaction on a semiquinone radical: stable semiquinone radicals
      serve as novel molecular platforms on which a Norrish-type-II photoreaction can
      be initiated. A detailed reaction scheme involving a 1,5-hydrogen transfer
      followed by a cyclization step that finally leads to a new C-C bond formation
      could be verified. Transient absorption spectroscopy and DFT calculations trace
      convincingly the intermediates and transition states along the reaction path.

PMID- 22991273
TI  - A new report of Cornelia de Lange syndrome associated with split hand and feet.
AB  - We report on a boy with clinical and molecular diagnosis of Cornelia de Lange
      syndrome (CdLS). Besides the CdLS typical features, he shows split hand and split
      feet. To the best of our knowledge, only one other patient with similar finding
      has been reported in CdLS patients.

PMID- 22991272
TI  - Signet ring cell mixed histology may show more aggressive behavior than other
      histologies in early gastric cancer.
AB  - BACKGROUND: Signet ring cell carcinoma (SRC) of the stomach is known to have
      different microscopic and biologic characteristics compared to non-SRC. The
      pathologic report has documented partly SRC component with main histologies.
      However, the clinical significance of SRC mixture has not been reported. Aim was
      to investigate clinicopathologic features of mixed-SRC histology in early gastric
      cancer (EGC). METHODS: Two thousand two hundred eight patients were diagnosed
      with EGC and underwent surgery. The patients were divided into three groups such
      as adenocarcinoma with partly SRC (mixed-SRC group), only adenocarcinoma
      (adenocarcinoma group), and SRC (SRC group). Clinicopathologic characteristics
      were compared. RESULTS: The SRC group was more associated with younger age,
      female, mid-body, mucosa-confined, depressed type, lower lymph node metastasis
      (LNM), lower lymphovascular invasion, and better survival rate than
      adenocarcinoma group. The mixed-SRC group was more associated with younger age,
      female, upper-body, and depressed type than adenocarcinoma group, similar to SRC
      group. However, the mixed-SRC group showed more submucosal invasion, larger size,
      and higher LNM than other groups. The mixed-SRC component was one of the
      independent risk factors of LNM. CONCLUSIONS: Mixed-SRC histology in EGC showed
      more aggressive behavior than other histologies. Clinical considerations of mixed
      SRC histology may be helpful to decide on a specific cancer treatment.

PMID- 22991274
TI  - PTH-enhanced structural allograft healing is associated with decreased
      angiopoietin-2-mediated arteriogenesis, mast cell accumulation, and fibrosis.
AB  - Recombinant parathyroid hormone (rPTH) therapy has been evaluated for skeletal
      repair in animal studies and clinical trials based on its known anabolic effects,
      but its effects on angiogenesis and fibrosis remain poorly understood. We
      examined the effects of rPTH therapy on blood vessel formation and osseous
      integration in a murine femoral allograft model, which caused a significant
      increase in small vessel numbers, and decreased large vessel formation (p <
      0.05). Histology showed that rPTH also reduced fibrosis around the allografts to
      similar levels observed in live autografts, and decreased mast cells at the graft
      host junction. Similar effects on vasculogenesis and fibrosis were observed in
      femoral allografts from Col1caPTHR transgenic mice. Gene expression profiling
      revealed rPTH-induced angiopoietin-1 (8-fold), while decreasing angiopoietin-2
      (70-fold) at day 7 of allograft healing. Finally, we show anti-angiopoietin-2
      peptibody (L1-10) treatment mimics rPTH effects on angiogenesis and fibrosis.
      Collectively, these findings show that intermittent rPTH treatment enhances
      structural allograft healing by two processes: (1) anabolic effects on new bone
      formation via small vessel angiogenesis, and (2) inhibition of angiopoietin-2
      mediated arteriogenesis. The latter effect may function as a vascular sieve to
      limit mast cell access to the site of tissue repair, which decreases fibrosis
      around and between the fractured ends of bone. Thus, rPTH therapy may be
      generalizable to all forms of tissue repair that suffer from limited
      biointegration and excessive fibrosis.

PMID- 22991275
TI  - Statistical considerations in biosimilar clinical efficacy trials with
      asymmetrical margins.
AB  - Development of biosimilars to innovative therapeutic biologics promises reduction
      of healthcare cost and therefore will provide patients worldwide greater access
      to effective treatments. Because of the differences in raw materials or
      manufacturing processes, 'equivalence' of bioavailability between a biosimilar
      and the reference biologic is generally regarded as insufficient, and thus,
      clinical trials providing efficacy and safety data are often required by
      regulatory agencies. The traditional non-inferiority trial design may not be
      accepted for establishing biosimilarity in order to avoid superior efficacy with
      additional safety (e.g., immunogenicity) risks. On the other hand, the
      bioequivalence trial design, which is used in the generic paradigm for the
      evaluation of bioavailability of generic chemical drugs, is not appropriate for
      evaluating clinical efficacy because the equivalence margins are generally too
      wide and not justified on statistical or clinical grounds. Motivated by the World
      Health Organization guideline and the newly released Food and Drug Administration
      draft guideline on biosimilars, we propose a biosimilarity trial design for
      evaluating clinical efficacy. The design uses a non-inferiority margin and an
      asymmetrical non-superiority margin for statistical inference. The independent
      choice of both margins provides the scientific foundation for drawing clinical
      efficacy conclusions while maintaining the logical consistency of the inference.
      The design also has a higher statistical power than a naive equivalence trial
      design.

PMID- 22991276
TI  - The effect of topically applied antimycotic agents on inner ear vestibular and
      cochlear function.
AB  - OBJECTIVES/HYPOTHESIS: To assess and compare the effect of commonly used topical
      antimycotic agents and their solvents on the function of the vestibular and
      cochlear parts of the sand rat's inner ear. STUDY DESIGN: Prospective,
      controlled, animal study. METHODS: Forty-five fat sand rats were randomly
      assigned to five major groups, each receiving topical application of a different
      agent: saline (control), gentamicin (ototoxic control), and three antimycotic
      agents: nystatin, clotrimazole solution (Agisten), and bifonazole solution
      (Agispor). All animals underwent a right labyrinthectomy, and a polyethylene tube
      was inserted into the left middle ear followed by baseline recording of
      vestibular evoked potentials (VsEPs) and auditory nerve and brainstem responses
      (ABR). Subsequently, each animal received five consecutive daily applications of
      the specific agent into the left middle ear. Evoked potential recordings were
      repeated 3 and 10 days after the last application and compared to baseline. For
      clotrimazole and bifonazole solutions, the effect of the solvents was assessed by
      comparing ABR recordings at similar intervals. RESULTS: Administration of saline
      did not affect VsEPs or ABR. Both could not be recorded following gentamicin
      application. In all three antimycotic agents, no statistically significant
      difference was found between VsEPs recordings before and after application.
      Clotrimazole and bifonazole solutions caused a significant ABR threshold
      elevation similar to that caused by their solvents. Nystatin caused a less
      significant ABR threshold elevation. CONCLUSIONS: The three commonly used topical
      antimycotic agents investigated here did not affect vestibular function but had a
      toxic effect on inner ear cochlear function. It seems the main offenders were the
      solvents.

PMID- 22991277
TI  - A process for updating a philosophy of education statement.
AB  - Most health education specialists have been introduced to the idea of having a
      philosophy of education statement. Although some in the field have been writing
      about this career development exercise, little has been written about the process
      of developing one's philosophy of education statement. This brief essay explains
      a sample process health education specialists can use to create or update their
      philosophy of education statement. The author gives a firsthand account of a
      systematic, disciplined, intellectually liberating, and reflective approach to
      articulating one's philosophy of education statement, by considering the writings
      of select intellectual giants who have acted on human experience, thought, and
      practice in education. A philosophy of education statement should be useful to
      any health education specialist regardless of type of work, site, position in the
      organization, population served, or health topic. The resultant updated and
      precisely written statement serves to sharpen a health education specialist's
      future role as a health educator, as well as contribute to his or her journey in
      lifelong learning.

PMID- 22991278
TI  - Promoting correct car seat use in parents of young children: challenges,
      recommendations, and implications for health communication.
AB  - Injuries involving motor vehicles continue to be the biggest threat to the safety
      of children. Although child safety seats (CSS) have been established as a central
      countermeasure in decreasing injury risk, the majority of parents do not use the
      correct car seat correctly. There are many challenges in promoting correct car
      seat use, which itself is a complex behavior. To advance this critical protective
      behavior, the public health community would benefit from clarifying CSS
      messaging, communicating clearly, and addressing the conflicting recommendations
      of product use. In this article, we present current challenges in promoting CSS
      use and draw on health communication and other fields to offer recommendations
      for future work in this area.

PMID- 22991280
TI  - School wellness policy implementation: insights and recommendations from two
      rural school districts.
AB  - Although school wellness policies have the potential to transform school
      environments, relatively little has been written about postadoption policy
      implementation and evaluation (policy to practice). The authors report results of
      a research study that examined the implementation of school wellness policies in
      two school districts in northern New Mexico. Through nine key informant
      interviews with administrators and two focus groups with students, they found
      that physical activity and nutrition policies were implemented inconsistently in
      both districts. Study participants identified facilitating factors (e.g.,
      champions, grant funding) and barriers (e.g., competitive food sales, lack of
      clarity about responsibility for policy enforcement) to policy implementation.
      Participants also provided recommendations to improve policy implementation,
      including wellness policy training for school personnel and parents, improving
      the taste, nutritional value of, and choices in cafeteria food; and involving the
      community health council to promote community understanding and support of the
      policies. This study underscores the need to identify and address factors
      involved in the successful implementation of school wellness policies, looking at
      schools in the larger context of their communities. It also serves as an example
      of the potential for communities, schools, and others to work together to address
      a locally identified health priority. 

PMID- 22991279
TI  - Developing a comprehensive curriculum for public health advocacy.
AB  - There is a substantial gap in public health school curricula regarding advocacy.
      Development of such a curriculum faces three challenges: faculty lack advocacy
      skills and experience; the public health literature on effective advocacy is
      limited; and yet a successful curriculum must be scalable to meet the needs of
      approximately 9,000 public health students graduating each year. To meet these
      challenges, we propose a 100-hour interactive online curriculum in five sections:
      campaigning and organizing, policy making and lobbying, campaign communications,
      new media, and fund-raising. We outline the content for individual modules in
      each of these sections, describe how the curriculum would build on existing
      interactive learning and social media technologies, and provide readers the
      opportunity to "test-drive" excerpts of a module on "grasstops" organizing.
      Developing advocacy skills and expertise is critical to meeting the challenges of
      public health today, and we provide a blueprint for how such training might be
      brought to scale in the field.

PMID- 22991281
TI  - Synthesis of 3-fluoropyrrolidines and 4-fluoropyrrolidin-2-ones from allylic
      fluorides.
AB  - Various 3-fluoropyrrolidines and 4-fluoropyrrolidin-2-ones were prepared by 5-exo
      trig iodocyclisation from allylic fluorides bearing a pending nitrogen
      nucleophile. These bench-stable precursors were made accessible upon
      electrophilic fluorination of the corresponding allylsilanes. The presence of the
      allylic fluorine substituent induces syn-stereocontrol upon iodocyclisation with
      diastereomeric ratios ranging from 10:1 to > 20:1 for all N-tosyl-3-fluoropent-4
      en-1-amines and amides. The sense and level of stereocontrol is strikingly
      similar to the corresponding iodocyclisation of structurally related allylic
      fluorides bearing pending oxygen nucleophiles. These results suggest that the syn
      selectivity observed upon ring closure involves I(2)-pi complexes with the
      fluorine positioned inside.

PMID- 22991282
TI  - Sinusoidal obstruction syndrome: correct dosing of monocrotaline and the validity
      of the rat model.

PMID- 22991283
TI  - The gamma-carbonic anhydrase subcomplex of mitochondrial complex I is essential
      for development and important for photomorphogenesis of Arabidopsis.
AB  - Complex I (NADH:ubiquinone oxidoreductase) is the entry point for electrons into
      the respiratory electron transport chain; therefore, it plays a central role in
      cellular energy metabolism. Complex I from different organisms has a similar
      basic structure. However, an extra structural module, referred to as the gamma
      carbonic anhydrase (gammaCA) subcomplex, is found in the mitochondrial complex I
      of photoautotrophic eukaryotes, such as green alga and plants, but not in that of
      the heterotrophic eukaryotes, such as fungi and mammals. It has been proposed
      that the gammaCA subcomplex is required for the light-dependent life style of
      photoautotrophic eukaryotes, but this hypothesis has not been successfully
      tested. We report here a genetic study of the genes gammaCAL1 and gammaCAL2 that
      encode two subunits of the gammaCA subcomplex of mitochondrial complex I. We
      found that mutations of gammaCAL1 and gammaCAL2 in Arabidopsis (Arabidopsis
      thaliana) result in defective embryogenesis and nongerminating seeds,
      demonstrating the functional significance of the gammaCA subcomplex of
      mitochondrial complex I in plant development. Surprisingly, we also found that
      reduced expression of gammaCAL1 and gammaCAL2 genes altered photomorphogenic
      development. The gammacal1 mutant plant expressing the RNA interference construct
      of the gammaCAL2 gene showed a partial constitutive photomorphogenic phenotype in
      young seedlings and a reduced photoperiodic sensitivity in adult plants. The
      involvement of the gammaCA subcomplex of mitochondrial complex I in plant
      photomorphogenesis and the possible evolutionary significance of this plant
      specific mitochondrial protein complex are discussed.

PMID- 22991285
TI  - Screening for long-term cardiac status during cancer treatment.

PMID- 22991286
TI  - Point-of-care echocardiography in the accountable care organization era.

PMID- 22991284
TI  - Cells and iron oxide nanoparticles on the move: magnetic resonance imaging of
      monocyte homing and myocardial inflammation in patients with ST-elevation
      myocardial infarction.

PMID- 22991287
TI  - High-resolution [18]fluorodeoxyglucose-positron emission tomography and
      coregistered magnetic resonance imaging of atherosclerotic plaque from a patient
      undergoing carotid endarterectomy.

PMID- 22991288
TI  - Pigs-in-a-blanket coronary arteries: a case of immunoglobulin G4-related coronary
      periarteritis assessed by computed tomography coronary angiography, intravascular
      ultrasound, and positron emission tomography.

PMID- 22991290
TI  - Letter by Puntmann et al regarding article, "Prevalence and clinical profile of
      myocardial crypts in hypertrophic cardiomyopathy".

PMID- 22991292
TI  - Death rates in the U.S. due to Krabbe disease and related leukodystrophy and
      lysosomal storage diseases.
AB  - Leukodystrophies (LD) and lysosomal storage disorders (LSD) have generated
      increased interest recently as targets for newborn screening programs. Accurate
      epidemiological benchmarks are needed in the U.S. Age-specific mortality rates
      were estimated for Krabbe disease (KD) and nine related disorders. U.S. mortality
      records with E75.2 cause of death code during 1999-2004 were collected from 11
      open record states. All E75.2 deaths in the United States were distributed into
      specific disease type based on proportions observed in these states. Yearly
      population sizes were obtained from the CDC and averaged. Mortality rates (per
      million individuals per year) by age group for the specific diseases were (for <5
      or >=5 years): Pelizaeus-Merzbacher (0.037/0.033); sudanophilic leukodystrophy
      (SLD) (0.037/0.004); Canavan (0.037/0.011), Alexander (0.147/0.022); Krabbe
      (0.994/0.007); metachromatic leukodystrophy (0.331/0.135); Fabry (0.000/0.124);
      Gaucher (0.221/0.073); Niemann-Pick (NP) (0.442/0.088); multiple sulfatase
      (0.000/0.004). This is the first report of mortality rates for the LD/LSD
      diseases in the U.S. Approximated birth prevalence rate for the early infantile
      Krabbe phenotype (onset 0-6 months) was based on the <5 year old mortality rate
      of one early infantile case per 244,000 births, which matches the 1 in 250,000
      observed in the NYS newborn screening program as of 2011. It should be noted
      however that the NYS calculation refers only to the early infantile phenotype and
      does not include the majority of babies identified in the program with low GALC
      and two mutations who have remained clinically normal. It is presumed that most,
      if not all, will develop later onset forms of the disease, but this is by no
      means certain.

PMID- 22991294
TI  - The learning curve of robotic lobectomy.
AB  - BACKGROUND: Robotic lobectomy has been shown to be feasible, safe and
      oncologically efficacious. The actual learning curve of robotic lobectomy has yet
      to be defined. This study was designed to define the learning curve of robotic
      lobectomy. METHODS: We performed a retrospective review of prospectively accrued
      patients at our institution who underwent robotic lobectomy from January 2004
      until December 2011. Six scatter graphs were constructed, comparing operative
      time, conversion rate, morbidity, mortality, length of stay and surgeon comfort
      with the number of consecutive cases. In each graph, a regression trendline was
      drawn and the change in the slope of the curve corresponding to the beginning of
      the plateau defined the learning curve. The overall learning curve was defined as
      mean +/- SD of the sum of the individual learning curves. RESULTS: Based on
      operative times, mortality and surgeon comfort, the overall learning curve was 18
      +/- 3 cases. The learning curve based on operative times, mortality and surgeon
      comfort was 15, 20 and 19 cases, respectively. There was no association between
      the need for conversion and number of consecutive cases. There was a trend
      towards lower morbidity and decreased length of stay with greater experience.
      However, these parameters did not define a specific learning curve. CONCLUSIONS:
      Operative time, mortality and surgeon comfort were found to be key parameters for
      the learning curve of robotic lobectomy when performed by surgeons who are
      experienced with video-assisted thoracic surgery (VATS). The learning curve was
      18 +/- 3 cases.

PMID- 22991293
TI  - Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin
      fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia.
AB  - X-linked hypophosphatemia (XLH/HYP)-with renal phosphate wasting,
      hypophosphatemia, osteomalacia, and tooth abscesses-is caused by mutations in the
      zinc-metallopeptidase PHEX gene (phosphate-regulating gene with homologies to
      endopeptidase on the X chromosome). PHEX is highly expressed by mineralized
      tissue cells. Inactivating mutations in PHEX lead to distal renal effects
      (implying accumulation of a secreted, circulating phosphaturic factor) and
      accumulation in bone and teeth of mineralization-inhibiting, acidic serine- and
      aspartate-rich motif (ASARM)-containing peptides, which are proteolytically
      derived from the mineral-binding matrix proteins of the SIBLING family (small,
      integrin-binding ligand N-linked glycoproteins). Although the latter observation
      suggests a local, direct matrix effect for PHEX, its physiologically relevant
      substrate protein(s) have not been identified. Here, we investigated two SIBLING
      proteins containing the ASARM motif-osteopontin (OPN) and bone sialoprotein (BSP)
      as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and
      mass spectrometry, we report that OPN is a full-length protein substrate for
      PHEX. Degradation of OPN was essentially complete, including hydrolysis of the
      ASARM motif, resulting in only very small residual fragments. Western blotting of
      Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity
      clearly showed accumulation of an ~35 kDa OPN fragment that was not present in
      wild-type mouse bone. Immunohistochemistry and immunogold labeling (electron
      microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its
      fragments compared with normal wild-type bone. Incubation of Hyp mouse bone
      extracts with PHEX resulted in the complete degradation of these fragments. In
      conclusion, these results identify full-length OPN and its fragments as novel,
      physiologically relevant substrates for PHEX, suggesting that accumulation of
      mineralization-inhibiting OPN fragments may contribute to the mineralization
      defect seen in the osteomalacic bone characteristic of XLH/HYP.

PMID- 22991297
TI  - First bite syndrome caused by adenoid cystic carcinoma of the submandibular
      gland.
AB  - First bite syndrome is a well-described sequelae of parapharyngeal space surgery,
      thought to result from sympathetic denervation of the parotid gland. We describe
      a case of first bite syndrome caused by an adenoid cystic carcinoma of the
      submandibular gland. The tumor was not clinically or radiographically apparent
      until 18 months after initial presentation despite repeated imaging. In patients
      with first bite syndrome and no surgical history, there must be high suspicion
      for a malignancy, which may be occult on presentation. The submandibular gland
      should be considered as a possible site of a lesion.

PMID- 22991298
TI  - Conformational analysis of fluorinated pyrrolidines using 19F-1H scalar couplings
      and heteronuclear NOEs.
AB  - A series of 3-fluoropyrrolidines have been studied to investigate the influence
      of the stereoelectronic fluorine gauche effect on ring conformations in the solid
      state by single-crystal X-ray analysis and in solution phase by NMR spectroscopy.
      As part of these studies 1D (19)F-(1)H heteronuclear NOE (HOESY) experiments have
      been optimised for applications to small molecules and are described in detail.
      These have been employed to estimate (19)F-(1)H internuclear distances and were
      combined with vicinal (3)J(F,H) and (3)J(H,H) scalar coupling constants to
      analyse the ring conformations. Where possible the derived solution-phase
      structural data have been compared with those of the crystalline state. The
      results demonstrate the influence of the gauche effect in stabilising C(gamma)
      exo conformations of the fluorinated pyrrolidines. It was further shown that when
      steric interactions were also present, this conformational bias was diminished
      and the contribution of the alternative C(gamma)-endo conformation was seen to
      increase in solution at lower sample temperatures.

PMID- 22991299
TI  - Podoplanin expression and its emerging role as a prognostic indicator in systemic
      tumors besides head and neck malignancies.

PMID- 22991300
TI  - Aphonia, microstomia, deafness, retinal dystrophy, duplicated halluces and
      intellectual disability.
AB  - We report on a sister and brother born to healthy, double first cousin Iranian
      parents with a seemingly unique combination of signs and symptoms consisting of
      intellectual disability, congenital absent voice (aphonia), hearing loss, optic
      atrophy, retinal dystrophy, mildly broad thumbs, and duplicated halluces. Their
      facial morphology was unusual: thick eyebrows, ptosis, full eyelashes, long
      palpebral fissures, downslanting palpebral fissures, small mouth, and low-set,
      posteriorly rotated ears. This phenotype does not meet the diagnostic criteria of
      any known entity. Because of parental consanguinity, absence of manifestations in
      parents, and occurrence in sibs of opposite sex, an autosomal recessive pattern
      of inheritance is likely.

PMID- 22991301
TI  - Tooth root dentin mineralization defects in a mouse model of hypophosphatasia.
AB  - Tissue-nonspecific alkaline phosphatase (TNAP) is expressed in mineralizing
      tissues and functions to reduce pyrophosphate (PP(i) ), a potent inhibitor of
      mineralization. Loss of TNAP function causes hypophosphatasia (HPP), a heritable
      disorder marked by increased PP(i) , resulting in rickets and osteomalacia. Tooth
      root cementum defects are well described in both HPP patients and in Alpl(-/-)
      mice, a model for infantile HPP. In Alpl(-/-) mice, dentin mineralization is
      specifically delayed in the root; however, reports from human HPP patients are
      variable and inconsistent regarding dentin defects. In the current study, we
      aimed to define the molecular basis for changes in dentinogenesis observed in
      Alpl(-/-) mice. TNAP was found to be highly expressed by mature odontoblasts, and
      Alpl(-/-) molar and incisor roots featured defective dentin mineralization,
      ranging from a mild delay to severely disturbed root dentinogenesis. Lack of
      mantle dentin mineralization was associated with disordered and dysmorphic
      odontoblasts having disrupted expression of marker genes osteocalcin and dentin
      sialophosphoprotein. The formation of, initiation of mineralization within, and
      rupture of matrix vesicles in Alpl(-/-) dentin matrix was not affected.
      Osteopontin (OPN), an inhibitor of mineralization that contributes to the
      skeletal pathology in Alpl(-/-) mice, was present in the generally unmineralized
      Alpl(-/-) mantle dentin at ruptured mineralizing matrix vesicles, as detected by
      immunohistochemistry and by immunogold labeling. However, ablating the OPN
      encoding Spp1 gene in Alpl(-/-) mice was insufficient to rescue the dentin
      mineralization defect. Administration of bioengineered mineral-targeting human
      TNAP (ENB-0040) to Alpl(-/-) mice corrected defective dentin mineralization in
      the molar roots. These studies reveal that TNAP participates in root dentin
      formation and confirm that reduction of PP(i) during dentinogenesis is necessary
      for odontoblast differentiation, dentin matrix secretion, and mineralization.
      Furthermore, these results elucidate developmental mechanisms underlying dentin
      pathology in HPP patients, and begin to explain the reported variability in the
      dentin/pulp complex pathology in these patients.

PMID- 22991302
TI  - Viral RNA patterns and high viral load reliably define oropharynx carcinomas with
      active HPV16 involvement.
AB  - Oropharyngeal squamous cell carcinomas (OPSCC) that are associated with human
      papilloma virus (HPV) infection carry a more favorable prognosis than those that
      are HPV-negative. However, it remains unclear which biomarker(s) can reliably
      determine which OPSCC specimens are truly driven by HPV infection. In this study,
      we analyzed 199 fresh-frozen OPSCC specimens for HPV DNA, viral load, RNA
      expression patterns typical for cervical carcinomas (CxCaRNA(+)), and the HPV
      targeted tumor suppressor protein p16(INK4a) as markers for HPV infection. In
      this set of specimens, there was a 49% prevalence of DNA for the cancer
      associated HPV type 16 (HPV(+)). However, there was only a 16% prevalence of high
      viral load and only a 20% prevalence of CxCaRNA(+), a marker of HPV16
      carcinogenic activity. Among the CxCaRNA(+) tumors, 78% of the specimens
      exhibited overexpression of p16(INK4a), which also occurred in 14% of the HPV
      negative tumors. Using a multivariate survival analysis with HPV negativity as
      the reference group, CxCaRNA(+) as a single marker conferred the lowest risk of
      death [HR = 0.28, 95% confidence interval (CI), 0.13-0.61] from oropharyngeal
      cancer, closely followed by high viral load (HR = 0.32, 95% CI, 0.14-0.73). In
      contrast, a weaker inverse association was found for OPSCC that were HPV(+) and
      p16(INK4a) high (HR = 0.55, 95% CI, 0.29-1.08). In summary, our findings argued
      that viral load or RNA pattern analysis is better suited than p16(INK4a)
      expression to identify HPV16-driven tumors in OPSCC patient populations.

PMID- 22991303
TI  - Biomarkers of HPV infection in oropharyngeal carcinomas: can we find simplicity
      in the puzzle of complexity?

PMID- 22991305
TI  - Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities
      in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of
      esophageal cancer, is a devastating disease characterized by distinctly high
      incidences and mortality rates. However, there remains limited understanding of
      molecular events leading to development and progression of the disease, which are
      of paramount importance to defining biomarkers for diagnosis, prognosis, and
      personalized treatment. By high-throughout transcriptome sequence profiling of
      nontumor and ESCC clinical samples, we identified a subset of significantly
      differentially expressed genes involved in integrin signaling. The Rab25 gene
      implicated in endocytic recycling of integrins was the only gene in this group
      significantly downregulated, and its downregulation was confirmed as a frequent
      event in a second larger cohort of ESCC tumor specimens by quantitative real-time
      PCR and immunohistochemical analyses. Reduced expression of Rab25 correlated with
      decreased overall survival and was also documented in ESCC cell lines compared
      with pooled normal tissues. Demethylation treatment and bisulfite genomic
      sequencing analyses revealed that downregulation of Rab25 expression in both ESCC
      cell lines and clinical samples was associated with promoter hypermethylation.
      Functional studies using lentiviral-based overexpression and suppression systems
      lent direct support of Rab25 to function as an important tumor suppressor with
      both anti-invasive and -angiogenic abilities, through a deregulated FAK-Raf
      MEK1/2-ERK signaling pathway. Further characterization of Rab25 may provide a
      prognostic biomarker for ESCC outcome prediction and a novel therapeutic target
      in ESCC treatment.

PMID- 22991304
TI  - Biomarkers of HPV in head and neck squamous cell carcinoma.
AB  - Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell
      carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable
      prognosis. Currently, there is no general guidance on the most appropriate
      biomarkers for clinical assessment of HPV in these malignancies. We compared PCR
      based and serologic HPV assays, as well as p16 immunohistochemistry, individually
      and in combination in a single population-based study to assess their
      associations with overall survival among patients with HNSCC, and thus their
      potential value as biomarkers. HPV16 serology was determined for 488 patients;
      immunohistochemical detection of p16 expression in tumors was conducted in a
      subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in
      a subset of 179 cases of tumors. Considering each biomarker individually in the
      subset of patients studied for all endpoints, seropositivity for the E6 and E7
      proteins was significantly associated with enhanced all-cause survival in
      oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02
      0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated
      with significant enhanced overall survival in oropharyngeal disease (HR(DNA) =
      0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination
      of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall
      survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0),
      whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not
      show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6
      18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had
      favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI =
      0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had
      significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1,
      95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis
      (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is
      defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in
      combination rather using tumor HPV status alone.

PMID- 22991306
TI  - Preliminary study of a novel method for conveying corrected image volumes in
      surgical navigation.
AB  - BACKGROUND: Commercial image-guided surgery systems rely on the fundamental
      assumption that preoperative medical images represent the physical state of the
      patient in the operating room. The guidance display typically consists of a three
      dimensional (3D) model derived from medical images and three orthogonal views of
      the imaging data. A challenging question in image-guided surgery is: what happens
      when the images used in the guidance display no longer correspond to the current
      geometric state of the anatomy and guidance information is still desirable?
      METHODS: We modify the conventional display with two techniques for incorporating
      a displacement field from a finite-element model into the guidance display and
      present a preliminary study of the effect of our method on performance with a
      simple surgical task. The topic of this paper is methods for conveying the
      computational model solution, not the model itself. To address the integration of
      the computational model solution into the display, a novel method of applying the
      deformation to the tool tip was developed, which quickly corrects for deformation
      but also maintains the pristine nature of the preoperative images. We compare the
      proposed technique to an existing method that applies the deformation field to
      the image volume. RESULTS: A pilot study compared mean performance with our
      method of applying the deformation to the tool tip and the conventional
      technique. These methods were statistically similar with respect to accuracy of
      localization (p < 0.05) and amount of time (p < 0.05) required for localization
      of the target. CONCLUSIONS: These results suggest that our new technique can be
      used in place of the computationally expensive task of deforming the image
      volume, without affecting the time or accuracy of the surgical task. Most
      notably, our work addresses the problem of incorporating deformation correction
      into the guidance display and offers a first step toward understanding its effect
      on surgical performance.

PMID- 22991307
TI  - Conflict of interests: multiple signal peptides with diverging goals.
AB  - Peptide signal sequences attached to or embedded into a core protein sequence
      control its cellular localization and several post-translational modifications.
      However, misleading or cumbersome results may be generated when expressing
      recombinant proteins with modified signal peptides or single domains of larger
      proteins.

PMID- 22991308
TI  - The edible red alga, Gracilaria verrucosa, inhibits lipid accumulation and ROS
      production, but improves glucose uptake in 3T3-L1 cells.
AB  - Gracilaria verrucosa is a red alga that is widely distributed in seaside areas of
      many countries. We examined the effect of G. verrucosa extract on adipogenesis,
      reactive oxygen species (ROS) production, and glucose uptake in 3T3-L1 cells. Oil
      red O staining and a nitroblue tetrazolium assay showed that G. verrucosa extract
      inhibited lipid accumulation and ROS production, respectively. mRNA levels of
      adipogenic transcription factors, peroxisome proliferator-activated receptor
      gamma and CCAAT/enhancer-binding protein alpha, as well as of their target gene,
      adipocyte protein 2, were reduced upon treatment with G. verrucosa extract.
      However, G. verrucosa extract increased glucose uptake, glucose transporter-4
      expression, and AMP-activated protein kinasealpha (AMPKalpha) phosphorylation
      compared to the control. Our results suggest that the anti-adipogenic and insulin
      sensitive effects of G. verrucosa extract can be recapitulated to activation of
      AMPKalpha.

PMID- 22991309
TI  - Outcomes following resection of pancreatic cancer.
AB  - Pancreatic cancer is an aggressive and highly lethal malignancy. Surgical
      resection is a modest tool, but it provides the only potential for curative
      therapy and often prolongs survival. This article reviews the progress made on
      both local and national levels towards an era of safer pancreatic surgery, while
      discussing both perioperative outcomes and long-term survival after resection.

PMID- 22991310
TI  - Using social marketing to increase awareness of the African American infant
      mortality disparity.
AB  - BACKGROUND: African American infants in San Francisco suffer a mortality rate two
      to three times higher than Whites, yet prior discussion groups with African
      American residents suggested they were unaware of this disparity. METHODS: Social
      marketing techniques were used to develop and implement three campaigns to
      increase awareness. The campaign themes were (1) infant mortality disparities,
      (2) proper infant sleep position, and (3) taking action to reduce disparities.
      Mediums to carry messages included bus ads, radio ads, church fans, and posters
      and cards distributed at clinics, daycares, agency waiting rooms, and community
      organizations. Campaign effectiveness was evaluated using telephone surveys of
      African Americans. RESULTS: Almost 62% report some exposure to Campaign 1, 48.5%
      to Campaign 2, and 48.9% to Campaign 3. Chi-square analyses reveal a
      statistically ignificant increase in awareness of the disparity (39.6% vs. 62.7%,
      p < .0005, odds ratio [OR] = 2.5, confidence interval [CI] = 2.1-3.2). Although
      there was no overall significant increase in knowledge about proper sleep
      position, respondents who report any exposure to this campaign are more likely to
      know about sleep position (70.7% vs. 63.8%, p < .0001, OR = 2.2, CI = 1.6-3.2).
      CONCLUSIONS: Social marketing is an effective tool to increase disparity
      awareness, especially among groups disproportionately affected by the disparity.

PMID- 22991311
TI  - A summative report of applications submitted for the experience documentation
      opportunity for the master certified health education specialist credential.
AB  - The purpose of this article is to provide a summative report of the applications
      submitted for the Experience Documentation Opportunity (EDO), implemented by the
      National Commission for Health Education Credentialing, Inc. (NCHEC). The EDO was
      a one-time, 6-month opportunity for health education specialists holding the
      entry-level certification (Certified Health Education Specialist or CHES) for 5
      or more continuous years, with active status, to submit documentation to verify
      practice at the advanced level to become a Master Certified Health Education
      Specialist (MCHES), the new advanced certification. The EDO process was rigorous
      and effective in verifying a professional's level of practice. A total of 862
      applications were submitted to NCHEC; 819 were approved, 36 denied, and 7
      withdrew. Frequency distributions indicate which advanced-level subcompetencies
      were used the most and least for applications. Results of the EDO process provide
      valuable information regarding characteristics of the first cohort of MCHES, as
      well as a direct assessment of advanced-level practice in the field of health
      education.

PMID- 22991312
TI  - Relative contributions of gender and traumatic life experience to the prediction
      of mental disorders in a sample of incarcerated offenders.
AB  - The objective of this study was to quantify the relative contributions of gender
      and traumatic life experience to psychiatric disorders in a sample of 320
      offenders entering a state prison. Women were more likely than men to report
      traumatic events and personal and family mental health treatment histories; and
      were more likely to meet criteria for posttraumatic stress, borderline
      personality, and eating disorders. People reporting traumatic life experiences
      were more likely than those not so reporting to have family mental histories and
      to meet criteria for mood, anxiety, psychotic, antisocial personality, and
      borderline personality disorders, as well as elevated suicide risk. With both
      gender and trauma included in the logistic regression models, only trauma was a
      significant predictor of mood, anxiety, psychotic, attention deficit
      hyperactivity, and antisocial personality disorders, as well as suicide risk.
      Trauma-informed programming, regardless of gender, is important for incarcerated
      offenders. To the extent that trauma is also criminogenic, these data suggest
      that women and men share the risk.

PMID- 22991313
TI  - The US postmarketing surveillance study of adult osteosarcoma and teriparatide:
      study design and findings from the first 7 years.
AB  - The Osteosarcoma Surveillance Study, an ongoing 15-year surveillance study
      initiated in 2003, is a postmarketing commitment to the United States (US) Food
      and Drug Administration to evaluate a potential association between teriparatide,
      rhPTH(1-34), a recombinant human parathyroid hormone analog (self-injectable
      medication to treat osteoporosis), and development of osteosarcoma in response to
      a finding from preclinical (animal) studies. Incident cases of primary
      osteosarcoma diagnosed in adults (aged >=40 years) on or after January 1, 2003,
      are identified through population-based state, regional, and comprehensive cancer
      center registries in the US. Information on possible prior treatment with
      teriparatide, on demographics, and on risk factors is ascertained by patient or
      proxy telephone interview after patient consent. Between June 2004 and September
      30, 2011, 1448 cases (diagnosed 2003 to 2009) were identified by participating
      cancer registries (estimated to be 62% of all adult cases in the US for that time
      period); 549 patients or proxies were interviewed. Interviewed patients were
      similar to noninterviewed patients with regard to mean age, sex, race, and
      geographical distribution and tumor type and site of tumor. Mean age of those
      interviewed was 61 years, 46% were female, 86% were white, and 77% were alive
      when the case was reported to the study investigators. Data collected in the
      study provide descriptive information on a large number of adults with
      osteosarcoma, an uncommon malignant bone tumor. After 7 years of the study, there
      were no osteosarcoma patients who had a prior history of teriparatide treatment.
      Thus, approximately halfway through this 15-year study, the study has not
      detected a pattern indicative of a causal association between teriparatide
      treatment and osteosarcoma in humans.

PMID- 22991314
TI  - Processing of superparamagnetic iron contrast agent ferucarbotran in transplanted
      pancreatic islets.
AB  - Labeling of pancreatic islets with superparamagnetic iron oxide (SPIO)
      nanoparticles enables their post-transplant monitoring by magnetic resonance
      imaging (MRI). Although the nanoparticles are incorporated into islet cells in
      culture, little is known about their fate in vivo. We studied the morphology of
      labeled islets after transplantation, aiming to identify the MRI contrast
      particles and their relationship to transplantation outcomes. Rat islets labeled
      with the ferucarbotran were transplanted into the liver or under the kidney
      capsule of syngeneic and allogeneic rats. After in vivo MRI, morphology was
      studied by light, fluorescence and transmission electron microscopy. Morphology
      of syngeneic islets transplanted beneath the kidney capsule vs into the liver was
      similar. Iron particles were almost completely eliminated from the endocrine
      cells and remained located in host-derived macrophages surrounding the vital
      islets for the entire study period. In the allogeneic model, islets lost their
      function and were completely rejected within nine days following transplantation
      in both transplant models. However, intercellular transport of the SPIO particles
      and subsequent MRI findings was different in the liver and kidney. In the liver,
      the decreasing number of islet-related MRI spots corresponded with clearance of
      iron particles in rejected islets; in contrast, with renal transplants extensive
      iron deposits with a high effect on MRI signal persisted in phagocytic cells
      beneath the capsule. We conclude that MRI detection of the iron contrast agent
      correlates with islet survival and function in islet transplantation into the
      liver, while it does not correlate in the case of transplantation beneath the
      renal capsule.

PMID- 22991315
TI  - Comparison of dynamic contrast-enhanced MRI and quantitative SPECT in a rat
      glioma model.
AB  - Pharmacokinetic modeling of dynamic contrast-enhanced (DCE) MRI data provides
      measures of the extracellular-extravascular volume fraction (v(e) ) and the
      volume transfer constant (K(trans) ) in a given tissue. These parameter estimates
      may be biased, however, by confounding issues such as contrast agent and tissue
      water dynamics, or assumptions of vascularization and perfusion made by the
      commonly used model. In contrast to MRI, radiotracer imaging with SPECT is
      insensitive to water dynamics. A quantitative dual-isotope SPECT technique was
      developed to obtain an estimate of v(e) in a rat glioma model for comparison with
      the corresponding estimates obtained using DCE-MRI with a vascular input function
      and reference region model. Both DCE-MRI methods produced consistently larger
      estimates of v(e) in comparison to the SPECT estimates, and several experimental
      sources were postulated to contribute to these differences.

PMID- 22991317
TI  - Two forms of iron as an intrinsic contrast agent in the basal ganglia of PKAN
      patients.
AB  - Iron deposits in the human brain can be considered as intrinsic contrast agents
      for magnetic resonance imaging and are used as markers of neurodegeneration
      accompanied by brain-iron accumulation. We studied one of them - panthotenate
      kinase associated neurodegeneration (PKAN) - by using relaxometry at 1.5, 3.0 and
      7 T in a group of six patients; we also measured a group of five volunteers for
      comparison. Based on the magnetic field dependency of antiferromagnetic ferritin
      and maghemite iron oxide nanoparticle relaxivities, we derived a two-component
      model for the description of iron deposits in the globus pallidus of PKAN
      patients. According to this model, we estimated the iron content in PKAN patients
      as 391 ug/ml of antiferromagnetic iron (ferritin) and 1.1 ug/ml of ferrimagnetic
      iron, compared with 178 ug/ml of iron in ferritin found in controls. This two
      component model explains the nonlinear shape of the relaxometric curves in in
      vivo measurements of the relaxation rates of PKAN patients and is supported by
      histological findings in the original reports on PKAN patients.

PMID- 22991316
TI  - Enhanced MRI relaxivity of Gd(3+) -based contrast agents geometrically confined
      within porous nanoconstructs.
AB  - Gadolinium chelates, which are currently approved for clinical MRI use, provide
      relaxivities well below their theoretical limit, and they also lack tissue
      specificity. Recently, the geometrical confinement of Gd(3+) -based contrast
      agents (CAs) within porous structures has been proposed as a novel, alternative
      strategy to improve relaxivity without chemical modification of the CA. Here, we
      have characterized and optimized the performance of MRI nanoconstructs obtained
      by loading [Gd(DTPA)(H(2) O)](2-) (Magnevist(r)) into the pores of injectable
      mesoporous silicon particles. Nanoconstructs with three different pore sizes were
      studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~24 m m(-1) 
      s(-1) for 5-10 nm pores and ~10 m m(-1)  s(-1) for 30 - 40 nm pores. No
      enhancement in relaxivity was observed for larger pores sizes. Using an outer
      sphere compound, [GdTTHA](3-) , and mathematical modeling, it was demonstrated
      that the relaxivity enhancement is due to the increase in rotational correlation
      times (CA adsorbed on the pore walls) and diffusion correlation times (reduced
      mobility of the water molecules), as the pore sizes decreases. It was also
      observed that extensive CA adsorption on the outer surface of the silicon
      particles negates the advantages offered by nanoscale confinement. Upon
      incubation with HeLa cells, the nanoconstructs did not demonstrate significant
      cytotoxicity for up to 3 days post incubation, at different particle/cell ratios.
      In addition, the nanoconstructs showed complete degradation after 24 h of
      continuous agitation in phosphate-buffered saline. These data support and confirm
      the hypothesis that the geometrical confinement of Gd(3+) -chelate compounds into
      porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6
      times for [Gd(DTPA)(H(2) O)](2-) , and 4 times for [GdTTHA](3-) ) and,
      potentially, improved stability, reduced toxicity and tissue specificity.

PMID- 22991318
TI  - cGMP-Compatible preparative scale synthesis of near-infrared fluorophores.
AB  - Image-guided surgery using optical imaging requires the availability of large
      quantities of clinical-grade fluorophores. We describe the cGMP-compatible
      synthesis of the zwitterionic heptamethine indocyanine near-infrared fluorophore
      ZW800-1 at the 10 g scale (~1000 patient doses) using facile and efficient
      solvent purification, and without the need for column chromatography. ZW800-1 has
      >90% yield at the final step and >99% purity as measured by fluorescence and
      evaporative light scatter detection. We describe an analytical framework for
      qualifying impurities, as well as a detailed analysis of counterion identities.
      Finally, we report the unique in vivo properties of ZW800-1 in large animals
      approaching the size of humans, thus laying the foundation for rapid clinical
      translation of these methods.

PMID- 22991320
TI  - Classification of acute and delayed contrast media-induced reactions: proposal of
      a three-step system.
AB  - Physicians and scientists use a broad spectrum of terms to classify contrast
      media (CM)-induced adverse reactions. In particular, the designation of
      hypersensitivity reactions is quite varied. Consequently, comparisons of
      different papers dealing with this subject are difficult or even impossible.
      Moreover, general descriptions may lead to problems in understanding reactions in
      patients with a history of adverse CM-reactions, and in efficiently managing
      these patients. Therefore, the goal of this paper is to suggest an easy system to
      clearly classify these reactions. The proposed three-step systems (3SS) is built
      up as follows: step 1 exactly describes the clinical features, including their
      severity; step 2 categorizes the time point of the onset (immediate or
      nonimmediate); and step 3 generally classifies the reaction (hypersensitivity or
      nonhypersensitivity reaction). The 3SS may facilitate better understanding of the
      clinical manifestations of adverse CM reactions and may support the prevention of
      these reactions on the basis of personalized medicine approaches.

PMID- 22991319
TI  - Optical imaging of progenitor cell homing to patient-derived tumors.
AB  - Capitalizing on cellular homing to cancer is a promising strategy for targeting
      malignant cells for diagnostic, monitoring and therapeutic purposes. Murine C17.2
      neural progenitor cells (NPC) demonstrate a tropism for cell line-derived tumors,
      but their affinity for patient-derived tumors is unknown. We tested the
      hypothesis that NPC accumulate in patient-derived tumors at levels detectable by
      optical imaging. Mice bearing solid tumors after transplantation with patient
      derived leukemia cells and untransplanted controls received 10(6) fluorescent DiR
      labeled NPC daily for 1-4 days, were imaged, then sacrificed. Tissues were
      analyzed by immunofluorescence and flow cytometry to detect tumor cell
      engraftment (CD45) and NPC (FITC-beta galactosidase or DiR). Tumors consisted
      primarily of CD45-positive cells and demonstrated mild fluorescence,
      corresponding to frequent clusters of FITC-beta gal-positive cells. Both
      transplanted and control mice demonstrated the highest fluorescent signal in the
      spleens and other tissues of the reticuloendothelial activating system. However,
      only rare FITC-beta gal-positive cells were detected in the mildly engrafted
      transplanted spleens and none in the control spleens, suggesting that their high
      DiR signal reflects the sequestration of DiR-positive debris. The mildly
      engrafted transplanted kidneys demonstrated low fluorescent signal and rare FITC
      beta gal-positive cells whereas control kidneys were negative. Results indicate
      that NPC accumulate in tissues containing patient-derived tumor cells in a manner
      that is detectable by ex vivo optical imaging and proportional to the level of
      tumor engraftment, suggesting a capacity to home to micrometastatic disease. As
      such, NPC could have significant clinical applications for the targeted diagnosis
      and treatment of cancer.

PMID- 22991321
TI  - Manganese: a new contrast agent for lung imaging?
AB  - Lung parenchyma remains one of the most difficult tissues to be imaged by means
      of magnetic resonance imaging (MRI). Several MRI techniques are routinely used
      for lung imaging. However, manganese-enhancement MRI (MEMRI) technique has not
      been associated with pulmonary MRI. Here, we evaluated T(1) -enhancement in the
      rat lung after a manganese instillation, using a 4.7 T magnet with a radial
      ultrashort echo time sequence. Our data showed that the signal intensity was
      increased in lungs receiving a manganese solution compared with a control
      solution to the lungs. MR signal enhancements above 30% were measured in lung
      parenchyma following 200 ul instillation of a 1 mm manganese chloride solution.
      MEMRI, therefore, may be a useful novel tool for enhancing signal intensity and
      image contrast in lung tissue.

PMID- 22991324
TI  - New spectrofluorimetric method for determination of cephalosporins in
      pharmaceutical formulations.
AB  - A simple, accurate, precise spectrofluorimetric method has been proposed for the
      determination of three cephalosporins, namely, cefixime (cefi), cephalexine
      (ceph), and cefotaxime sodium (cefo) in pharmaceutical formulations. This method
      is based on a reaction between cephalosporins with 8-hydroxy-1,3,6
      pyrenetrisulfonic acid trisodium salt (HPTS) in alkaline medium, at pH 12.0 for
      cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted
      with chloroform and subsequent measurements of the formed fluorescent products at
      520, 500 and 510 nm after excitation at 480, 470 and 480 nm for cefi, ceph and
      cefo respectively. The optimum experimental conditions have been studied. Beer's
      law is obeyed over concentrations of 10-60 ng/mL, 5-35 ng/mL and 10-60 ng/mL for
      cefi, ceph and cefo, respectively. The detection limits were 4.20 ng/mL, 2.54
      ng/mL and 4.09 ng/mL for cefi, ceph and cefo, respectively, with a linear
      regression correlation coefficient of 0.99783, 0.99705 and 0.9978 and recoveries
      in ranges 96.96-105.77, 96.13-102.55 and 95.45-105.39% for cefi, ceph and cefo,
      respectively. This method is simple and can be applied for the determination of
      cefi, ceph and cefo in pharmaceutical formulations in quality control
      laboratories.

PMID- 22991325
TI  - Anti-microbial activity and composition of manuka and portobello honey.
AB  - Recently renewed interest in the therapeutic properties of honey has led to the
      search for new antimicrobial honeys. This study was undertaken to assess the
      antimicrobial activity and composition of a locally produced Portobello honey
      (PBH) on three bacteria known to infect wounds. Manuka honey (MH) was used for
      comparative purposes. Broth culture and agar disc diffusion assays were used to
      investigate the antimicrobial properties of honey. The honeys were tested at four
      concentrations: 75%, 50%, 10% and 1% (v/v) and compared with an untreated
      control. The composition of honey was determined by measuring: polyphenol content
      by Folin Ciocalteau method, antioxidant capacity by ferric ion reducing power
      assay, hydrogen peroxide (H2 O2 ) by catalase test, pH and sugar content by pH
      strips and refractometer, respectively. Both honeys at 75% and 50% inhibited the
      majority of the three bacteria tested. 10% PBH exhibited antimicrobial activity
      to the lesser extent than 10% MH. The difference was very significant (p <=
      0.001). Both honeys were acidic with pH 4, and both produced H2 O2 . The sugar
      content of PBH was higher than MH, but the difference was not significant. The MH
      had significantly higher levels of the polyphenols and antioxidant activity than
      PBH.

PMID- 22991323
TI  - Insights into imaging of aortitis.
AB  - BACKGROUND: Aortitis is a subtype of the more general term "vasculitis", an
      inflammatory condition of infectious or noninfectious origin involving the vessel
      wall. The term "vasculitis" refers to a broad spectrum of diseases with different
      aetiologies, pathophysiologies, clinical presentations and prognoses. The
      clinical manifestations are nonspecific, as are the laboratory findings such as
      pain, fever, weight loss, vascular insufficiency and elevated levels of acute
      phase reactants, as well as other systemic manifestations, and sometimes may
      mimic other entities. Thus, if not suspected as part of the initial differential
      diagnosis, aortitis can be overlooked during the workup of patients with
      constitutional symptoms and systemic disorders. METHODS: Imaging is rarely used
      for the primary diagnosis, but imaging findings, although nonspecific, can help
      in the assessment of these patients and is often required for making the final
      diagnosis. Imaging can be critical in the initiation of appropriate management
      and therapy. RESULTS: Noninvasive cross-sectional imaging modalities such as
      contrast-enhanced CT, magnetic resonance (MR) imaging, nuclear medicine and in
      particular positron emission tomography (PET) are the leading modalities in
      modern diagnostic imaging of aortitis for both the initial diagnosis and follow
      up. CONCLUSION: This review focusses on the most common manifestations of
      aortitis with which radiologists should be familiar. TEACHING POINTS : * Aortitis
      is an inflammatory condition of infectious/noninfectious origin involving the
      vessel wall. * Imaging findings can help in the assessment of aortitis and are
      often crucial for the final diagnosis. * Contrast-enhanced CT, MRI and PET-CT are
      used for both the initial diagnosis and follow-up of aortitis.

PMID- 22991326
TI  - Psycholegal abilities and restoration of competence to stand trial.
AB  - Criminal defendants adjudicated incompetent to stand trial are typically
      hospitalized for competence restoration in state institutions. Prolonged
      restoration hospitalizations involve civil rights concerns and increasing
      financial costs, and there remains interest in determining which individuals are
      likely to be successfully restored. We retrospectively reviewed hospital records
      of 455 male defendants admitted to a forensic treatment center for competence
      restoration in an effort to determine whether psychiatric diagnoses, demographic
      factors, or psycholegal abilities were predictive of successful or failed
      restoration. At varying stages of restoration efforts, psychotic disorder, mental
      retardation, and previous state hospitalization predicted unsuccessful
      restoration, while substance use and personality disorders were predictive of
      successful restoration. Psycholegal abilities were predictive of successful
      restoration and appeared to form a continuum, with basic behavior and outlook,
      factual legal understanding, and rational attorney assistance factors
      demonstrating progressively increased importance in successful restoration.

PMID- 22991328
TI  - Lesson learned from 10 years' experience in laparoscopic appendectomy in a
      community hospital.
AB  - The debate between open and laparoscopic appendectomy is now overtook by the need
      of a standardized technique, as laparoscopy, in the elective and emergency
      setting, is widely disseminated thorough surgical practices. A retrospective
      review of a 10 years' case history (838 laparoscopic appendectomies) is analyzed,
      and the last 5 years experience (300 cases) compared to the previous experience
      after the adoption of a standardized technique, which comprehends an all-comers
      policy without patients' selection prior to explorative laparoscopy. No post
      operative infections have been recorded, neither intra-abdominal abscesses nor
      wound infections, in the laparoscopic group. Significant differences (p < 0.05)
      have been found between the rate of peritonitis and male sex, elderly patients,
      and the use of stapler for the treatment of the appendiceal stump. Also
      conversion to laparotomy has been associated with complicated appendicitis, while
      associated diseases are found more frequently in fertile women. No differences in
      the operating time have been evidenced between laparoscopic, open or converted
      appendectomy. We sustain that every patient with a suspect of appendicitis should
      have a laparoscopic chance, indeed maintaining a low threshold for conversion;
      and that surgical indication should be anticipated for male and elderly patients,
      in order to lower the rate of complicated appendicitis.

PMID- 22991329
TI  - Laparoscopic ligation of splenic artery aneurysms: report of two cases and
      literature overview.

PMID- 22991330
TI  - Can peripheral blood gammadelta T cells predict osteonecrosis of the jaw? An
      immunological perspective on the adverse drug effects of aminobisphosphonate
      therapy.
AB  - Nitrogen-bisphosphonates (n-BP), often referred to as aminobisphosphonates, are
      the most commonly prescribed drugs for the treatment of disorders of bone
      fragility. However, long-term continuous treatment predisposes certain
      individuals to serious rare side effects, such as bisphosphonate-associated
      osteonecrosis of the jaw (BAONJ). n-BP use is known to unintentionally activate a
      subset of innate T cells called Vgamma9Vdelta2 T cells, but the consequence of
      this chronic immune stimulation has remained unexplored. The primary objectives
      of this study were to 1) determine the fate of Vgamma9Vdelta2 T cells in
      osteoporotic patients on n-BP therapy as a function of time and type of therapy;
      2) evaluate the proportion of Vgamma9Vdelta2 T cells in patients who had recently
      experienced n-BP-associated ONJ. We found there is a notable loss of
      Vgamma9Vdelta2 T cells over time in osteoporotic patients on n-BP therapy,
      particularly those on intravenous (iv) therapy (Spearman r = -0.55, p < 0.0001
      iv; r = -0.3, p < 0.03 oral) (n = 68); no difference was observed in total T
      cells, monocytes, or granulocytes. Importantly, the observed negative effect on
      Vgamma9Vdelta2 T cells coincides with the reported route of administration and
      timing of the rare occurrence of BAONJ. Patients (n = 6) who had experienced
      BAONJ were all found to be significantly deficient in Vgamma9Vdelta2 T cells
      (median = 0.07%) in comparison to age- and sex-matched treatment-naive controls
      (N = 11; median = 2.40%), U = 0, p = 0.001; this was the only consistent
      difference in the leukocytes assessed. All BAONJ cases had an underlying
      condition that further contributed to impaired immunity. We propose
      Vgamma9Vdelta2 T cells show a strong potential to serve as harbingers of possible
      adverse immune effects of n-BP therapy, particularly in those patients already
      having a compromised immune system as they may be most vulnerable to the
      development of conditions such as BAONJ.

PMID- 22991327
TI  - Computational analysis of noncoding RNAs.
AB  - Noncoding RNAs have emerged as important key players in the cell. Understanding
      their surprisingly diverse range of functions is challenging for experimental and
      computational biology. Here, we review computational methods to analyze noncoding
      RNAs. The topics covered include basic and advanced techniques to predict RNA
      structures, annotation of noncoding RNAs in genomic data, mining RNA-seq data for
      novel transcripts and prediction of transcript structures, computational aspects
      of microRNAs, and database resources.

PMID- 22991331
TI  - Increased sphingoid base-1-phosphates and failure of neural tube closure after
      exposure to fumonisin or FTY720.
AB  - BACKGROUND: Fumonisin B(1) (FB(1)) is a mycotoxin produced by a common fungal
      contaminant of corn. Ingestion of FB(1)-contaminated food is associated with
      increased risk for neural tube defects (NTDs). FB(1) induces NTDs in inbred LM/Bc
      mice. FB(1) inhibits ceramide synthase in de novo sphingolipid biosynthesis,
      resulting in accumulation of sphinganine and sphinganine-1-phosphate (Sa1P). Sa1P
      functions as a ligand for a family of G protein-coupled S1P receptors. METHODS:
      Pregnant SWV and LM/Bc mice were treated with FB(1) (20 mg/kg/day
      intraperitoneally on embryonic day (ED) 7.5-8.5) or the known S1P receptor
      agonist FTY720 (10 mg/kg/day oral gavage on ED 6.5-8.5). LC/MS was used to detect
      sphingoid base-1-phosphates in maternal blood spots, plasma, and embryonic
      tissue. Strain-specific SWV and LM/Bc mouse embryonic fibroblasts (MEFs) and
      serum free mouse embryo (SFME) neural progenitor cells were treated with FB(1)
      (40 MUM for 24 hr) and LC/MS was used to detect sphingoid base-1-phosphates.
      RESULTS: FTY720 induced NTDs in both the SWV and the LM/Bc strains of mice.
      Sphinganine-1-P (Sa1P) and FTY720-P were elevated in the blood spots and plasma
      of mice treated with FB(1) or FTY720, respectively. FTY720-P was elevated in ED
      9.5 exencephalic embryos. Sa1P was elevated in SFME and MEF cells treated with
      FB(1), and Sa1P was higher in MEFs generated from the FB(1)-NTD-susceptible LM/Bc
      strain. CONCLUSIONS: Elevated sphingoid base-1-P after FB(1) or FTY720 suggest a
      potential role for these bioactive lipid ligands and activation of S1P receptor
      signaling pathways in the failure of neural tube closure after FB(1) or FTY720.
      Sa1P may represent a biomarker for FB(1)-NTD risk assessment.

PMID- 22991332
TI  - Bioassay-guided supercritical fluid extraction of cyclooxygenase-2 inhibiting
      substances in Plantago major L.
AB  - INTRODUCTION: Selective extraction of plant materials is advantageous for
      obtaining extracts enriched with desired constituents, thereby reducing the need
      for subsequent chromatography purification. Such compounds include three
      cyclooxygenase-2 (COX-2) inhibitory substances in Plantago major L. targeted in
      this investigation: alpha-linolenic acid (alpha-LNA) (18:3 omega-3) and the
      triterpenic acids ursolic acid and oleanolic acid. OBJECTIVE: To investigate the
      scope for tuning the selectivity of supercritical fluid extraction (SFE) using
      bioassay guidance, and Soxhlet extraction with dichloromethane as solvent as a
      reference technique, to optimise yields of these substances. METHOD: Extraction
      parameters were varied to optimise extracts' COX-2/COX-1 inhibitory effect
      ratios. The crude extracts were purified initially using a solid phase extraction
      (SPE) clean-up procedure and the target compounds were identified with GC-MS, LC
      ESI-MS and LC-ESI-MS2 using GC-FID for quantification. RESULTS: alpha-LNA was
      preferentially extracted in dynamic mode using unmodified carbon dioxide at 40
      degrees C and 172 bar, at a 0.04% (w/w) yield with a COX-2/COX-1 inhibitory
      effect ratio of 1.5. Ursolic and oleanolic acids were dynamically extracted at
      0.25% and 0.06% yields, respectively, with no traces of (alpha-LNA) and a COX
      2/COX-1-inhibitory effect ratio of 1.1 using 10% (v/v) ethanol as polar modifier
      at 75 degrees C and 483 bar. The Soxhlet extracts had ursolic acid, oleanolic
      acid and alphaLNA yields up to 1.36%, 0.34% and 0.15%, respectively, with a COX
      2/COX-1 inhibitory effect ratio of 1.2. CONCLUSION: The target substances can be
      extracted selectively by bioassay guided optimisation of SFE conditions.

PMID- 22991333
TI  - Does the 'coupled clock' make the heart tick?

PMID- 22991334
TI  - Mass spectrometry made easy: the quest for simplicity.
AB  - Mass spectrometry (MS) is generally viewed as a highly complex and demanding
      technique, full of difficulties and apprehensions. Ease and simplicity have been
      infrequently used descriptors of MS but a series of revolutionary developments is
      turning a complex technique into a model of simplicity, making MS easier than
      ever. Focusing on spray-based ambient desorption/ionization techniques, we
      discuss how previously unthinkable goals for MS - (1) to bring it to a real world
      open atmosphere environment; (2) to perform fast, selective, and highly sensitive
      chemical and biochemical MS analysis with ease while (3) avoiding pre-separation
      and sample work-up for samples in their natural environment and therefore, at the
      end, (4) to make MS accessible in wherever MS is needed and by whoever needs it -
      have become feasible. Without compromising the unique combination of high speed,
      selectivity, sensitivity and separation competences, simplicity has become a new
      MS attribute - a fifth 'S' in the unique 5 S set of MS trademark features.

PMID- 22991335
TI  - Alterated talar and navicular bone morphology is associated with pes planus
      deformity: a CT-scan study.
AB  - We compared bone and articular morphology of the talus and navicular in
      clinically diagnosed flatfeet and evaluated their potential contribution to talo
      navicular joint instability. We used CT images to develop 3D models of talus and
      navicular bones of 10 clinically diagnosed flatfeet and 15 non-flatfeet. We
      quantified their global bone dimensions, inclination and dimensions of the
      articular surfaces and their curvatures. Additionally, ratios of six talar and
      navicular dimensions were calculated. The values for these parameters were then
      compared between both groups. In flatfeet, the talar head faced more proximal and
      its width was larger compared to non-flatfeet. Also the navicular cup faced more
      proximal and its depth was significantly increased. Furthermore, we observed a
      more protruding talar head compared to the navicular cup in the control group
      with the articular surface depth being relatively larger for the navicular cups
      when compared to the talus in flatfeet. The ratio of the talar and navicular
      articular surface height was decreased in flatfeet, suggesting increased height
      of navicular cups relative to the articulating talar heads. Our results show that
      flatfoot deformity is associated with morphological changes of talar and
      navicular articular surfaces that can favor medial arch collapse and forefoot
      abduction.

PMID- 22991337
TI  - Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth
      in asymptomatic singleton pregnant women with a history of preterm birth and a
      sonographic short cervix.
AB  - OBJECTIVE: To compare the outcome of pregnancy in cohorts of women with singleton
      pregnancy and history of preterm birth and sonographic short cervix managed with
      different treatment protocols, namely cerclage, vaginal progesterone or cervical
      pessary. METHODS: This was a comparison of three management protocols for women
      with singleton pregnancy and a high risk of preterm birth because of a prior
      spontaneous preterm birth before 34 weeks and a shortened cervical length
      detected by transvaginal ultrasound. The study included 142 women who were
      initially treated with cerclage (USA), 59 with vaginal progesterone (UK) and 42
      with cervical pessary (Spain). Perinatal outcomes were compared between the three
      cohorts. RESULTS: There were no statistically significant differences in
      perinatal losses, neonatal morbidity and preterm births among the three groups,
      apart from a higher rate of preterm birth before 34 weeks' gestation after
      treatment with vaginal progesterone in comparison with treatment with cervical
      pessary (32% vs 12%; relative risk (RR) = 2.70; 95% CI, 1.10-6.67). When only the
      subgroups of women with cervical length < 25 mm, irrespective of gestational age,
      were compared, the difference between these two cohorts was not statistically
      significant (RR = 2.21; 95% CI, 0.83-5.89). CONCLUSION: Cerclage, vaginal
      progesterone and pessary appear to have similar effectiveness as management
      strategies in women with singleton pregnancy, previous spontaneous preterm birth
      and short cervix. Direct randomized comparisons of these strategies, or
      combinations thereof, are needed to determine optimal management.

PMID- 22991336
TI  - Possible role of interleukin-17 in a prime/challenge model of multiple sclerosis.
AB  - No one single pathogen has been identified as the causative agent of multiple
      sclerosis (MS). Alternately, the likelihood of an autoimmune event may be
      nonspecifically enhanced by different infectious agents. In a novel animal model
      of MS, SJL/J mice primed through infection with a recombinant vaccinia virus (VV)
      encoding myelin proteolipid protein (PLP) (VV(PLP)) were susceptible to a central
      nervous system (CNS) inflammatory disease following administration of a
      nonspecific immunostimulant [complete Freund's adjuvant (CFA) plus Bordetella
      pertussis (BP)]. Mononuclear cells isolated from the brains, but not the spleens,
      of VV(PLP)-primed CFA/BP challenged mice produced interleukin (IL)-17 and
      interferon-gamma and transferred a CNS inflammatory disease to naive SJL/J mice.
      Administration of curdlan, a T helper 17 cell inducer, unexpectedly resulted in
      less severe clinical and histological signs of disease, compared to CFA/BP
      challenged mice, despite the induction of IL-17 in the periphery. Further
      examination of the VV(PLP)-prime CFA/BP challenge model may suggest new
      mechanisms for how different pathogens associated with MS can protect or enhance
      disease.

PMID- 22991338
TI  - A redox proteomic investigation of oxidative stress caused by benzoylecgonine in
      the freshwater bivalve Dreissena polymorpha.
AB  - Drugs of abuse and their human metabolites have been recently recognized as
      emerging environmental contaminants. Notwithstanding the fact that these kinds of
      compounds share some features with pharmaceuticals, their ecotoxicology has not
      yet been extensively investigated, although some of their characteristics may
      potentially threaten aquatic ecosystems. One of the most abundant drugs found in
      rivers and wastewaters is benzoylecgonine (BE), the main metabolite of cocaine.
      We applied a redox proteomics approach to evaluate changes in the proteome of
      Dreissena polymorpha exposed to two different concentrations of BE (0.5 and 1
      ug/l). Exposures were performed in vivo for a period of 14 days and the effect of
      oxidative stress on protein thiol and carbonyl groups in mussel gills were
      evaluated. One-dimensional electrophoresis did not reveal a reduction in protein
      thiol content but showed a significant increase of protein carbonylation at both
      doses tested. Then, protein profiling using two-dimensional gel electrophoresis
      was performed with subsequent matrix assisted laser desorption/ionization time-of
      flight (MALDI-TOF) and TOF/TOF with LIFT technique and linear ion trap combined
      with orbitrap mass spectrometer (LTQ-Orbitrap). This yielded de novo protein
      sequences suitable for database searching. These preliminary results and protein
      identifications obtained suggest that BE causes oxidative stress. Oxidative
      modifications were detected in differing classes of proteins such as those of the
      cytoskeleton, energetic metabolism and stress response.

PMID- 22991340
TI  - The role of TNXB single-nucleotide polymorphisms in recurrent shoulder
      dislocation.
AB  - Tenascin-X (TNX) is an extra-cellular matrix glycoprotein associated with
      collagen fibril deposition. Recent reports have linked truncated TNX mutations
      (TNXB) to generalized joint hypermobility and most importantly recurrent joint
      dislocation. In the present study, we investigated whether there is an
      association between joint dislocation recurrence rate and the frequency of TNXB
      single-nucleotide polymorphisms (SNPs). Seventy-eight patients treated for post
      traumatic shoulder instability and 82 healthy controls were genotyped for
      selected TNXB SNP using TaqMan(r) Genotyping Assays. At a mean follow-up of 24
      months recurrence rate and clinical outcomes were evaluated using the Constant
      and Murley, Rowe, and DASH scores. The association between genotypes and joint
      dislocation was tested using the dominant, recessive and additive models, and the
      model-free approach. Genotype distribution of the examined SNPs did not
      significantly deviate from the Hardy-Weinberg equilibrium (HWE) neither in
      patients nor in the controls. Moreover, there was no significant difference in
      genotype and allele distribution between patients and controls. Finally, no
      difference in genotype frequency was detected between patients who experienced a
      re-dislocation after the initial surgery and patients who did not sustain a re
      dislocation. The SNPs investigated in this study have no clinically relevant
      influence on TNXB gene expression and/or TNX function. Therefore, these SNPs
      could not be used for predicting individual risk of recurrent shoulder
      dislocation.

PMID- 22991339
TI  - Notch gain of function inhibits chondrocyte differentiation via Rbpj-dependent
      suppression of Sox9.
AB  - Notch signaling plays a critical role during development by directing the binary
      cell fate decision between progenitors and differentiated cells. Previous studies
      have shown sustained Notch activation in cartilage leads to chondrodysplasia.
      Genetic evidence indicates that Notch regulates limb bud mesenchymal stem cell
      differentiation into chondrocytes via an Rbpj-dependent Notch pathway. However,
      it is still unknown how Notch governs chondrogenesis in the axial skeleton where
      Notch serves a primary patterning function. We hypothesized that both Rbpj
      dependent and Rbpj-independent Notch signaling mechanisms might be involved.
      Cartilage-specific Notch gain-of-function (GOF) mutant mice display
      chondrodysplasia accompanied by loss of Sox9 expression in vertebrae. To evaluate
      the contribution of an Rbpj-dependent Notch signaling to this phenotype, we
      deleted Rbpj on the Notch GOF background. These mice showed persistent spine
      abnormalities characterized by "butterfly" vertebrae suggesting that removal of
      Rbpj does not fully rescue the axial skeleton deformities caused by Notch GOF.
      However, Sox9 protein level was restored in Rbpj-deficient Notch GOF mice
      compared with Notch GOF mutants, demonstrating that regulation of Sox9 expression
      is canonical or Rbpj-dependent. To further understand the molecular basis of this
      regulation, we performed chromatin immunoprecipitation (ChIP) assays and detected
      the recruitment of the Rbpj/NICD transcription complex to Rbpj-binding sites
      upstream of the Sox9 promoter. The association of the Rbpj/NICD complex with the
      Sox9 promoter is associated with transcriptional repression of Sox9 in a cellular
      model of chondrocyte differentiation. Hence, Notch negatively regulates
      chondrocyte differentiation in the axial skeleton by suppressing Sox9
      transcription, and Rbpj-independent Notch signaling mechanisms may also
      contribute to axial skeletogenesis.

PMID- 22991345
TI  - Psychostimulant effect of levodopa: reversing sensitisation is possible.
AB  - BACKGROUND: Levodopa therapy in Parkinson's disease (PD) is associated with non
      motor complications resulting from sensitisation of the ventral striatum system.
      Recent studies showed an improvement in non-motor complications in PD patients
      with subthalamic stimulation. We hypothesised that ventral striatum
      desensitisation might contribute to this improvement. METHODS: Psychostimulant
      effects of levodopa were prospectively assessed in 36 PD patients with an acute
      levodopa challenge, before and 1 year after chronic subthalamic stimulation,
      using the Addiction Research Centre Inventory euphoria subscale. Postoperative
      evaluation was performed with the same dose of levodopa used in the preoperative
      assessment and after switching off stimulation. Preoperative and postoperative
      non-motor fluctuations in everyday life were investigated with the Ardouin Scale.
      Furthermore, in order to artificially reproduce non-motor fluctuations, a
      levodopa challenge keeping subthalamic stimulation on was performed to assess
      depression, anxiety and motivation before and after surgery under the different
      medication conditions. RESULTS: After 1 year of chronic subthalamic stimulation
      with 60.3% reduction in dopaminergic medication, the acute psychostimulant
      effects of levodopa were significantly reduced compared with preoperatively, as
      measured by the euphoria subscale (7.22 +/- 4.75 vs 4.75 +/- 5.68; p = 0.0110).
      On chronic subthalamic stimulation and with markedly reduced dopaminergic
      medication, non-motor fluctuations were significantly improved. While off
      medication/on stimulation scores of depression and anxiety were improved, in the
      on medication/on stimulation condition the motivation score worsened.
      CONCLUSIONS: Acute psychostimulant effects of levodopa (off stimulation) were
      significantly reduced 1 year after surgery. These findings are likely due to
      desensitisation of the ventral striatum, allowed by the reduction of dopaminergic
      treatment, and the replacement of pulsatile treatment with continuous subthalamic
      stimulation.

PMID- 22991346
TI  - Effects of extreme temperatures on years of life lost for cardiovascular deaths:
      a time series study in Brisbane, Australia.
AB  - BACKGROUND: Extreme temperatures are associated with cardiovascular disease (CVD)
      deaths. Previous studies have investigated the relative CVD mortality risk of
      temperature, but this risk is heavily influenced by deaths in frail elderly
      people. To better estimate the burden of extreme temperatures, we estimated their
      effects on years of life lost due to CVD. METHODS AND RESULTS: The data were
      daily observations on weather and CVD mortality for Brisbane, Australia, between
      1996 and 2004. We estimated the association between daily mean temperature and
      years of life lost due to CVD, after adjusting for trend, season, day of the
      week, and humidity. To examine the nonlinear and delayed effects of temperature,
      a distributed lag nonlinear model was used. The model's residuals were examined
      to investigate whether there were any added effects due to cold spells and heat
      waves. The exposure-response curve between temperature and years of life lost was
      U-shaped, with the lowest years of life lost at 24 degrees C. The curve had a
      sharper rise at extremes of heat than of cold. The effect of cold peaked 2 days
      after exposure, whereas the greatest effect of heat occurred on the day of
      exposure. There were significantly added effects of heat waves on years of life
      lost. CONCLUSIONS: Increased years of life lost due to CVD are associated with
      both cold and hot temperatures. Research on specific interventions is needed to
      reduce temperature-related years of life lost from CVD deaths.

PMID- 22991347
TI  - Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes:
      a substudy from the prospective randomized PLATelet inhibition and patient
      Outcomes (PLATO) trial.
AB  - BACKGROUND: Elderly patients with acute coronary syndrome are at high risk of
      recurrent ischemic events and death, and for both antithrombotic therapy and
      catheter-based complications. This prespecified analysis investigates the effect
      and treatment-related complications of ticagrelor versus clopidogrel in elderly
      patients (>=75 years of age) with acute coronary syndrome compared with those <75
      years of age. METHODS AND RESULTS: The association between age and the primary
      composite outcome, as well as major bleeding were evaluated in the PLATelet
      inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards.
      Similar models were used to evaluate the interaction of age with treatment
      effects. Hazard ratios were adjusted for baseline characteristics. The clinical
      benefit of ticagrelor over clopidogrel was not significantly different between
      patients aged >=75 years of age (n=2878) and those <75 years of age (n=15 744)
      with respect to the composite of cardiovascular death, myocardial infarction, or
      stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death
      (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No
      increase in PLATO-defined overall major bleeding with ticagrelor versus
      clopidogrel was observed in patients aged >=75 years (hazard ratio, 1.02; 95%
      confidence interval, 0.82-1.27) or patients aged <75 years (hazard ratio, 1.04;
      95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more
      common during ticagrelor than clopidogrel treatment, with no evidence of an age
      by-treatment interaction. CONCLUSIONS: The significant clinical benefit and
      overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome
      patients in the PLATO cohort were not found to depend on age.

PMID- 22991348
TI  - Registry studies for improving the quality of cardiovascular care: the role of
      variance components.

PMID- 22991349
TI  - Transitions, Risks, and Actions in Coronary Events--Center for Outcomes Research
      and Education (TRACE-CORE): design and rationale.
AB  - BACKGROUND: Cardiovascular disease continues to cause significant morbidity,
      mortality, and impaired quality of life, with unrealized health gains from the
      underuse of available evidence. The Transitions, Risks, and Actions in Coronary
      Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance
      the science of acute coronary syndromes by examining the determinants and
      outcomes of the quality of transition from hospital to community and by
      quantifying the impact of potentially modifiable characteristics associated with
      decreased quality of life, rehospitalization, and mortality. METHODS AND RESULTS:
      TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized
      with acute coronary syndromes, 2 research projects, and development of a nucleus
      of early stage investigators. We are currently enrolling 2500 adults hospitalized
      for acute coronary syndromes at 6 hospitals in the northeastern and southeastern
      United States. We will follow these patients for 24 months after hospitalization
      through medical record abstraction and 5 patient interviews focusing on quality
      of life, cardiac events, rehospitalizations, mortality, and medical, behavioral,
      and psychosocial characteristics. The Transitions Project studies determinants of
      and disparities in outcomes of the quality of patients' transition from hospital
      to community. Focusing on potentially modifiable factors, the Action Scores
      Project will develop and validate action scores to predict recurrent cardiac
      events, death, and quality of life, describe longitudinal variation in these
      scores, and develop a dashboard for patient and provider action on the basis of
      these scores. CONCLUSIONS: In TRACE-CORE, sound methodologic principles of
      observational studies converge with outcomes and effectiveness research
      approaches. We expect that our data, research infrastructure, and research
      projects will inform the development of novel secondary prevention approaches and
      underpin the careers of cardiovascular outcomes researchers.

PMID- 22991351
TI  - Bias in comparative effectiveness studies due to regional variation in medical
      practice intensity: a legitimate concern, or much ado about nothing?

PMID- 22991352
TI  - Most important outcomes research papers on anticoagulation for cardiovascular
      disease.
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 been 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 anticoagulation for cardiovascular disease.

PMID- 22991350
TI  - Rationale, design, and implementation of aggressive risk factor management in the
      Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in
      Intracranial Stenosis (SAMMPRIS) trial.

PMID- 22991353
TI  - Public health and sustainability.

PMID- 22991355
TI  - Celebrating the life of Sir Sandy Macara.

PMID- 22991356
TI  - More women giving birth later in life.

PMID- 22991357
TI  - Peep into policy, politics, Parliament.

PMID- 22991360
TI  - Conference report: managing water safety in healthcare: a snapshot of a
      conference by the Royal Society for Public Health.

PMID- 22991361
TI  - Postcard from New Zealand.

PMID- 22991362
TI  - Should alcoholic drinks be ordered and served in "units"?

PMID- 22991363
TI  - Public health and travel medicine: intricately intertwined.

PMID- 22991364
TI  - The role of public health in climate change and sustainability: is the UK public
      health community's response adequate?

PMID- 22991365
TI  - Adult attention deficit hyperactivity disorder (ADHD): public health
      implications.

PMID- 22991366
TI  - Menu engineering for assisted-living elderly: a public health imperative.

PMID- 22991367
TI  - Health in the NHS: lifestyle behaviours of hospital employees.

PMID- 22991368
TI  - Potentials of health impact assessment as a local health policy supporting tool.
AB  - Planning for health and creating healthy public policy has been one of the main
      priorities of the Healthy Cities Project since the early 1990s. The Healthy City
      Foundation of Pecs (Hungary) - as one of the founding cities of the Healthy
      Cities Project in Europe - has been involved in all phases of health profiling,
      health planning and health development planning throughout the years. The
      experiences of the Healthy Cities Project have strengthened the recognition that
      the decisions of elected local decision-making bodies are generally based on
      daily demands and not on long-term plans or concepts. The decision-making process
      has only one type of filtering system (operated by the city notary), which is for
      the preliminary legal control of the decisions to be made. Quality of life,
      health and equity are not considered in the system as a filtering issue. This
      article reports the experiences of the unique approach of health-orientated
      planning and decision making in the City of Pecs by using the method of health
      impact assessment (HIA) as a 'health filter'. It describes the initiative, the
      success of training and the feasibility of creating a health filter to support
      the local decision-making process.

PMID- 22991369
TI  - Engaging with marginalized communities: the experiences of London health
      trainers.
AB  - AIMS: Health trainers represent a new occupational role within the NHS which has
      been developing since 2006, when the first 'early adopter' sites were funded by
      the Department of Health. Health trainers are 'lay' people recruited to engage
      'harder-to-reach' people from their communities, offering one-to-one support to
      enable them to make the healthy lifestyle changes of their choice. The aim of
      this study was to explore the experiences and approaches adopted by health
      trainers in engaging with marginalized communities. METHODS: This paper describes
      an exploratory study using in-depth semi-structured interviews with 10 currently
      employed health trainers with diverse backgrounds, forms of employment and
      interpretation of role, drawn from seven London primary care trusts (PCTs) or
      boroughs. RESULTS: The study found tensions between the lay identity of health
      trainers and their adoption of a formalized role. Health trainers emphasized
      their similarities but underestimated their often significant differences to
      their communities. Health trainers based in community or voluntary groups found
      engagement easier than those based in PCTs, and saw engagement as an end in
      itself, through its creation of opportunities for health. CONCLUSIONS: There
      remains a lack of clarity about the role of the health trainer. Lay workers are
      not necessarily part of the marginalized communities they are expected to engage,
      while their ability to do so is compromised by the professional culture of the
      NHS and its approach to community engagement. Health trainers based in the
      community or voluntary sector appear to offer greater potential for engaging
      communities and providing those communities with practical opportunities for
      health gain.

PMID- 22991370
TI  - Development of a practical toolkit using participatory action research to address
      health inequalities through NGOs in the UK: Challenges and lessons learned.
AB  - This study aimed to develop a practical toolkit to support non-government
      organizations (NGOs) in tackling health inequalities in the UK and to highlight
      the challenges and lessons learned. A mixed qualitative methodology within an
      action research framework was conducted. Semi-structured questionnaires, focus
      group interviews and discussions with an expert reference group aimed to identify
      the important themes and produce the toolkit content. A practical guide of
      information materials for NGOs working on addressing health inequalities was
      subsequently developed and successfully piloted. The experience of using
      participatory action research revealed a number of lessons and challenges. The
      key challenges were lack of training and experience in conducting action
      research, costs and insufficient resources, slow and time-consuming process, lack
      of commitment from marginalized groups, and differences in emphasis of goals and
      vision among participants. The main lessons learned were importance of effective
      leadership and project management skills, importance of integrating researchers
      and the researched as equal partners, creation and nurturing of trust, importance
      of evaluating and piloting processes, importance of engaging with marginalized
      groups, and use of evidence base in decision making. The lessons and challenges
      enumerating herein are of value to researchers aiming to implement participatory
      action research in developing checklists, tools, practical guidance and
      frameworks, and they offer important areas to consider before starting such
      projects. In addition, this offers an insight into how the dynamics of
      participatory action research methodology evolved in the development of the
      toolkit. Future research and initiatives in this area should focus on ways to
      improve the toolkit and make it more relevant to a wider community, and methods
      for evaluating the impact of the toolkit on practice.

PMID- 22991371
TI  - A perspective on the future public health practitioner.
AB  - In the centuries following the Enlightenment, scientific and technological
      developments gave 'modern people' an unprecedented ability to understand, predict
      and control the natural world. This has brought health and social benefits
      unimaginable to our ancestors and sets us apart from all previous generations.
      Yet there is a wide-ranging body of evidence that suggests that modernity is now
      in decline, largely because its methods and mindset are increasingly recognized
      as unsustainable. Problems are manifest in the emergence of new public health
      epidemics such as obesity and addictive behaviours, the loss of well-being and
      increase in anxiety and depression in affluent society, and the persistence of
      ever-widening health and social inequalities at national and global levels. Still
      larger problems now confront us, such as climate change, peak oil and the loss of
      biodiversity, all of which are linked to the 'modern' way of life. We are
      potentially faced with the collapse of certain aspects of modern society: we are
      certainly faced with the prospect of inevitable change. While the broad public
      health community has an important role to play in developing workable solutions
      to such daunting problems, we argue that some profound changes will be needed in
      order for us to cope successfully. No blueprints for dealing with change exist,
      which means that we will need to learn our way into the future. In this paper we
      take a perspective on the role and nature of the future practitioner in public
      health and health promotion. We argue that future practitioners will need to
      develop new ways of thinking, being and doing; new perspectives and new forms of
      understanding the world. We believe our discipline - and people generally - to be
      capable of such development, as insights from multiple sources tell us that human
      nature is malleable, not fixed. We use this analysis to trace, as examples, the
      imagined lives of five women living in different eras over the course of history
      in a Western society, and the emergence of different mindsets or worldviews, as
      the social, economic and cultural context changes. Post-modern analysts might
      insist that we have no basis for making value judgements between such different
      worldviews. In this paper, however, we argue that future practitioners should be
      empathetic to different views and willing to move beyond them, as necessary. We
      will need to learn and develop in ways that are compatible with our intrinsic
      needs as human beings and the needs of our ecosystem. We conclude by suggesting
      just some of the supportive processes of change needed in mapping out a more
      sustainable future for the public health community.

PMID- 22991372
TI  - The effects of water shortages on health and human development.
AB  - Shortages of water could become a major obstacle to public health and
      development. Currently, the United Nations Children's Fund (UNICEF) and the World
      Health Organization (WHO) estimate that 1.1 billion people lack access to a water
      supply and 2.6 billion people lack adequate sanitation. The global health burden
      associated with these conditions is staggering, with an estimated 1.6 million
      deaths every year from diseases associated with lack of access to safe drinking
      water, inadequate sanitation and poor hygiene. In this paper we review the impact
      of water shortages on health and human development.

PMID- 22991373
TI  - Uncovering the potential of private providers' involvement in health to
      strengthen comprehensive health systems: a discussion paper.
AB  - Health systems strengthening (HSS) is being increasingly recognized as a
      strategic cross-cutting issue in all World Health Organization (WHO) work. Health
      systems comprise six building blocks: service delivery; medical products,
      vaccines and technologies; health workforce; health systems financing; health
      information system; and leadership and governance. Public-private mix (PPM)
      approaches or partnerships consist of initiatives aimed at increasing
      collaboration and improving the relationships between public-public, public
      private and private-private health providers. An important component of PPM is
      the clear distribution of tasks between the different providers involved in the
      provision of health care. In practice, most PPM initiatives are disease-specific
      and are often related to the health service delivery block mentioned above.
      Although there is widespread consensus that PPM initiatives are typically of an
      HSS nature, efforts to make explicit the links between PPM and health systems
      building blocks are rather uncommon. The present paper aims to identify - in
      order to facilitate operationalization - potential aspects linking PPM to health
      systems building blocks, using a few experiences from tuberculosis control and
      beyond. The paper targets policymakers, donors and health systems scientists and
      ends with a call for more aware and innovative leadership, for increased support
      of PPM initiatives covering various building blocks, and for more operational
      research.

PMID- 22991378
TI  - The bright and the dark sides of activin in wound healing and cancer.
AB  - Activin was initially described as a protein that stimulates release of follicle
      stimulating hormone from the pituitary, and it is well known for its important
      roles in different reproductive functions. In recent years, this multifunctional
      factor has attracted the attention of researchers in other fields, as new
      functions of activin in angiogenesis, inflammation, immunity, fibrosis and cancer
      have been discovered. Studies from our laboratory have identified activin as a
      crucial regulator of wound healing and skin carcinogenesis. On the one hand, it
      strongly accelerates the healing process of skin wounds but, on the other hand,
      it enhances scar formation and the susceptibility to skin tumorigenesis. Finally,
      results from several laboratories have revealed that activin enhances tumour
      formation and/or progression in some other organs, in particular through its
      effect on the tumour microenvironment, and that it also promotes cancer-induced
      bone disruption and muscle wasting. These findings provide the basis for the use
      of activin or its downstream targets for the improvement of impaired wound
      healing, and of activin antagonists for the prevention and treatment of fibrosis
      and of malignant tumours that overexpress activin. Here, we summarize the
      previously described roles of activin in wound healing and scar formation and
      discuss functional studies that revealed different functions of activin in the
      pathogenesis of cancer. The relevance of these findings for clinical applications
      will be highlighted.

PMID- 22991379
TI  - Noninvasive imaging of the meiotic spindle of in vivo matured oocytes from
      infertile women with endometriosis.
AB  - The objectives of this prospective study were to evaluate the nuclear maturation
      stage and the presence and location of meiotic spindles of in vivo matured
      oocytes from infertile women with and without endometriosis (male or tubal causes
      of infertility) undergoing stimulated cycles for intracytoplasmic sperm injection
      (ICSI). We also compared the ICSI outcomes among groups. We analyzed the meiotic
      spindles of oocytes from 36 patients with endometriosis I/II, 24 with
      endometriosis III/IV, and 60 without endometriosis (male or tubal causes of
      infertility). The oocytes were imaged using polarization microscopy. There were
      no differences in the number of oocytes in telophase I (mean [standard
      deviation]: 0.1 [0.5], 0.2 [0.4], and 0.2 [0.5], respectively, in the
      endometriosis I/II, endometriosis III/IV, and control groups), in metaphase II
      with visible spindles (4.2 [2.5], 3.1 [2.0], and 3.6 [2.2], respectively, in the
      endometriosis I/II, endometriosis III/IV, and control groups), and in spindle
      location among groups. We can conclude from this study that noninvasive analysis
      of spindles from in vivo matured oocytes of infertile patients with endometriosis
      did not demonstrate significant differences in terms of the nuclear maturation
      stage, the percentage of oocytes in metaphase II with visible spindles, and the
      spindle localization when compared to the control group. However, it is important
      to state that there are no studies evaluating the accuracy of polarization
      microscopy for the detection of meiotic anomalies in human oocytes, which would
      need to be better evaluated in future studies using an appropriate methodology.

PMID- 22991380
TI  - The effects of watermelon (Citrullus lanatus) extracts and L-citrulline on rat
      uterine contractility.
AB  - In uterine smooth muscle, the effects of watermelon and its citrulline content
      are unknown. The aims of this study were therefore, to determine the effects of
      watermelon extract and citrulline on the myometrium and to investigate their
      mechanisms of action. The effects of extracts of watermelon flesh and rind and L
      citrulline (64 MUmol/L) were evaluated on 3 types of contractile activity;
      spontaneous, those elicited by potassium chloride (KCl) depolarization, or
      oxytocin (10 nmol/L) application in isolated rat uterus. Inhibitors of nitric
      oxide (NO) and its mechanisms of action, N omega-Nitro-L-arginine methyl ester
      hydrochloride (L-NAME, 100 MUmol/L), LY83583 (1 MUmol/L), and tetraethylamonium
      chloride (5 mmol/L), as well as Ca signaling pathways, were determined. Both
      flesh and rind extracts significantly decreased the force produced by all 3
      mechanisms, in a dose-dependent manner. The extracts could also significantly
      decrease the force under conditions of sustained high Ca levels (depolarization
      and agonist) and when the force was produced only by sarcoplasmic reticulum (SR)
      Ca release. L-citrulline produced the same effects on force as watermelon
      extracts. With submaximal doses of extract, the additive effects of L-citrulline
      were found. The inhibitory effects of extracts and L-citrulline were reversed
      upon the addition of NO inhibitors, and pretreatment of tissues with these
      inhibitors prevented the actions of both extracts and L-citrulline. Thus, these
      data show that watermelon and citrulline are potent tocolytics, decreasing the
      force produced by calcium entry and SR release and arising by different pathways,
      including oxytocin stimulation. Their major mechanism is to stimulate the NO
      cyclic guanosine monophosphate (cGMP) relaxant pathway.

PMID- 22991381
TI  - Effects of angiogenic factors, antagonists, and podocyte injury on development of
      proteinuria in preeclampsia.
AB  - Proteinuria is universal to all patients with preeclampsia. We examined the
      urinary podocytes in women with preeclampsia (n = 14), gestational hypertension
      (n = 14), and normal pregnancy. Maternal serum and urinary concentrations of
      vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and
      the antiangiogenic factor soluble fms-like tyrosine kinase 1 (sFlt-1) were
      detected. These concentrations were used to evaluate the urinary excretion of
      podocytes and the alteration of angiogenic factors and to assess their
      relationships to proteinuria in preeclampsia. Our studies suggest that the
      urinary podocyte number and angiogenic factors are correlated with random urine
      albumin/creatinine ratio and blood pressure. Receiver-operating characteristic
      (ROC) curves of serum and urinary PlGF and the PlGF/sFlt-1 ratio as well as the
      presence of podocyturia confirmed their usefulness in distinguishing preeclamptic
      and normotensive pregnant women. In addition, combinations of serum or urinary
      PlGF or podocyturia tests in parallel or in series provided the best clue for
      identifying patients with preeclampsia. We considered that the dysregulation of
      angiogenic factors and its subsequent podocyte injury may contribute to the
      mechanism of proteinuria development in preeclampsia.

PMID- 22991382
TI  - Fetal pulmonary arterial vascular impedance reflects changes in fetal oxygenation
      at near-term gestation in a nonhuman primate model.
AB  - OBJECTIVE: We tested the hypothesis that fetal pulmonary arterial circulation
      reacts to changes in fetal oxygenation status at near-term gestation. STUDY
      DESIGN: A total of 20 rhesus macaques underwent fetal Doppler ultrasonography at
      near-term gestation. Right pulmonary artery (RPA), umbilical artery (UA), ductus
      arteriosus (DA), and ductus venosus (DV) blood velocity waveforms were obtained,
      and pulsatility index (PI) values were calculated. Fetal right and left
      ventricular cardiac outputs were determined. Ultrasonographic data were collected
      during 3 maternal oxygenation states: room air (baseline), hyperoxemia, and
      hypoxemia. RESULTS: Fetal RPA PI values increased (P < .05) during maternal
      hypoxemia and decreased (P < .05) during maternal hyperoxemia, compared with
      baseline. Maternal hyperoxemia increased (P < .05) DA PI values from baseline.
      Fetal cardiac outputs, UA, and DV PI values were not affected. CONCLUSIONS: Our
      results demonstrate that at near-term gestation, fetal pulmonary arterial
      circulation is a dynamic vascular bed that reflects acute and short-term changes
      in fetal oxygenation.

PMID- 22991383
TI  - Ultrasound-guided interstitial laser ablation for thyroid nodules is effective
      only at high total amounts of energy: results from a three-year pilot study.
AB  - OBJECTIVE: According to cross-sectional surveys, the prevalence of nontoxic
      nodular goiter appears to be higher in the adult population. Surgical
      intervention is indicated for the following: (a) progressive goiter growth, (b)
      compression of organs such as the trachea and esophagus, and (c) significant
      aesthetic disfigurement. Ultrasound-guided laser photocoagulation for the
      treatment of benign thyroid nodules is a viable alternative to traditional
      surgery. However, studies that have appeared in literature since the introduction
      of ultrasound-guided laser photocoagulation for the treatment of benign thyroid
      nodules report contradictory data concerning the energy required for nodule
      ablation. The aim of the present trial was to evaluate retrospectively the
      efficacy of percutaneous laser thermal ablation in 2 groups of patients, one
      treated with low, and the other with high, total amount of energy. DESIGN: Forty
      euthyroid patients were treated with 1 session of percutaneous laser
      photocoagulation treatment at low (median = 71 J/mL; 20 patients) and high
      (median = 578 J/mL; 20 patients) energy. The volume of the nodules was measured
      by the same investigator, blinded for treatment, using the ellipsoid formula
      before treatment, at 2, 4, 8, and 30 weeks, and every 6 months for 3 years
      thereafter. RESULTS: Thyroid nodule ablation is effective over time only if a
      sufficient amount of energy (>400-500 J/mL for the nodular tissue to be treated)
      is given, although it incurs proportionate side effects. CONCLUSIONS:
      Percutaneous laser thermal ablation is a viable alternative to traditional
      surgery for the treatment of benign nodular thyroid disease only if a sufficient
      amount of energy is delivered.

PMID- 22991384
TI  - The effects of natural orifice translumenal endoscopic surgery (NOTES) on
      cardiorespiratory physiology: a systematic review.
AB  - INTRODUCTION: Despite the increasing awareness of natural orifice translumenal
      endoscopic surgery (NOTES), there remain obstacles to its wider implementation.
      We aim to examine the current evidence for the effects of variable uncontrolled
      insufflation pressures using either air or carbon dioxide in NOTES, as well the
      effects of NOTES procedures themselves, on physiological parameters. METHOD: We
      undertook a systematic review of all publications relating to the effects of
      NOTES on physiology, in particular compared with laparoscopy. RESULTS: Eleven
      reports were identified comprising comparative trials involving a total of 237
      pigs. With one exception, no difference was found between the effect of NOTES and
      laparoscopic surgery on cardiopulmonary parameters. No difference was found also
      for the effect on inflammatory mediators such as interleukin-6. Two studies also
      assessed the effects choice of insufflation gas, with no change in inflammatory
      markers. Two further studies assessing the effects of variable pneumoperitoneal
      pressures found negative cardiorespiratory effects with higher pressures.
      DISCUSSION: Existing evidence is limited to small-sample animal trials but
      appears to show noninferiority for NOTES compared with laparoscopy. The
      development of a pressure regulation device for NOTES must be considered.

PMID- 22991385
TI  - Phenotypic modulation of cell types around implanted polyethylene terephthalate
      fabric in rabbit muscle.
AB  - Whereas the nature of healing reaction in skeletal muscle following implantation
      of biomaterial has been extensively studied, the extent of variation in cell
      phenotypes is poorly known. Here, we studied the phenotypic alteration of cell
      types following injury in skeletal muscle of rabbits implanted with a commonly
      used biomaterial, polyethylene terephthalate (PET) fabric. Following
      implantation, histomorphological features were studied after 1, 4, and 12 weeks.
      Routine objective histomorphological evaluation was supplemented with
      histochemistry for collagen and immunohistochemistry for proliferating cell
      nuclear antigen (PCNA), CD34, vimentin, and alpha smooth muscle actin (alpha
      SMA). The extent of reaction was quantified. The foreign body giant cells were
      found to comprise subpopulations, based on the variation in vimentin
      detectability or the presence of differentially capable proliferating nuclei
      (PCNA positive). Many rhabdomyocytes adjacent to the implant were PCNA-positive
      and some of them showed CD34 positivity. Often, the rhabdomyocytes very near to
      implanted PET fabric assumed a myofibroblast phenotype as evidenced by vimentin
      and/or alpha-SMA positivity at immunohistochemistry. Overall, the results
      suggested a phenotypic alteration of native cell types following implantation of
      PET fabric in rabbit skeletal muscle. Quantification of such cell types at the
      tissue-material interphase in relation to the deposition of collagen may be
      desirable during safety evaluation of biomaterials by histomorphology.

PMID- 22991386
TI  - Current practices in preclinical drug development: gaps in hemostasis testing to
      assess risk of thromboembolic injury.
AB  - The Health and Environmental Sciences Institute Cardiac Biomarkers Working Group
      surveyed the pharmaceutical development community to investigate practices in
      assessing hemostasis, including detection of hypocoagulable and hypercoagulable
      states. Scientists involved in discovery, preclinical, and clinical research were
      queried on laboratory evaluation of endothelium, platelets, coagulation, and
      fibrinolysis during safety assessment studies. Results indicated that laboratory
      assessment of hemostasis is inconsistent among institutions and not harmonized
      between preclinical and clinical studies. Hemostasis testing in preclinical drug
      safety studies primarily focuses on the risk of bleeding, whereas the clinical
      complication of thrombosis is seldom assessed. Our results reveal the need for
      broader utilization of biomarkers to detect altered hemostasis (e.g., endothelial
      and platelet activation) to improve preclinical safety assessments early in the
      drug development process. Survey respondents indicated a critical lack of
      validated markers of hypercoagulability and subclinical thrombosis in animal
      testing. Additional obstacles included limited blood volume, lack of cross
      reacting antibodies for hemostasis testing in laboratory species, restricted
      availability of specialized hemostasis analyzers, and few centers of expertise in
      animal hemostasis testing. Establishment of translatable biomarkers of
      prothrombotic states in multiple species and strategic implementation of testing
      on an industry-wide basis are needed to better avert untoward drug complications
      in patient populations.

PMID- 22991387
TI  - An indirect enzyme-linked immunosorbent assay using a recombinant truncated
      capsid protein of Porcine circovirus-2.
AB  - Porcine circovirus-2 (PCV-2) serology is commonly used for PCV-2 herd status
      determination and optimal timing of PCV-2 vaccination programs. The objectives of
      the current study were to develop an in-house indirect enzyme-linked
      immunosorbent assay (ELISA) using a recombinant nuclear localization signal
      truncated capsid (rntCap) protein expressed in an Escherichia coli system and to
      determine the diagnostic performance of the developed rntCap indirect ELISA in
      comparison with immunoperoxidase monolayer assays (IPMAs). Based on a receiver
      operating characteristic (ROC) curve analysis of the rntCap indirect ELISA (n =
      90), an optimum cutoff optical density (OD) of 0.330 was determined, which
      resulted in diagnostic sensitivity, diagnostic specificity, and accuracy of
      98.33%, 93.33%, and 96.67%, respectively. Average OD values of the positive (n =
      8) and negative sera (n = 8) tested by either purified glutathione-S-transferase
      (GST) protein or the rntCap protein as the coating antigen revealed that the mean
      OD values tested by the rntCap indirect ELISA were significantly different from
      using GST alone (P < 0.005). The correlation between the established rntCap
      indirect ELISA and the IPMA results demonstrated as the linear regression
      (Spearman correlation coefficient = 0.772, P < 0.005) indicated that the OD ratio
      obtained from the rntCap indirect ELISA could be used to predict the levels of
      the IPMA titers. More samples are needed for enhancing the diagnostic
      sensitivity, specificity and accuracy. In conclusion, the establishment of the
      rntCap indirect ELISA could be used as a serodiagnostic assay for large-scale
      detection of PCV-2 antibodies in swine and has the capability to be produced
      commercially for routine use in diagnostic laboratories.

PMID- 22991388
TI  - Crotalariosis equorum ("jaagsiekte") in horses in southern Mozambique, a rare
      form of pyrrolizidine alkaloid poisoning.
AB  - Twenty-eight horses in southern Mozambique died after exhibiting severe
      respiratory distress. At necropsy, the overinflated lungs did not collapse, had
      prominent rib impressions, and were fibrotic and emphysematous. Microscopically,
      prominent proliferation of nonciliated epithelial (Clara) cells in the terminal
      bronchioles and pulmonary fibrosis were observed, indicative of chronic
      pneumotoxicity. Transmission electron microscopy demonstrated hyperplasia,
      desquamation, and apical bulging of Clara cells into the bronchiolar lumen. The
      outbreak was attributed to ingestion of Crotalaria dura J.M. Wood & M.S. Evans
      subsp. mozambica Polhill and Crotalaria monteiroi Taub. ex Baker f. var.
      monteiroi. Semiquantitative gas chromatography-mass spectrometry revealed the
      presence of pyrrolizidine alkaloids in these 2 Crotalaria species.

PMID- 22991389
TI  - Susceptibility of cattle to the agent of chronic wasting disease from elk after
      intracranial inoculation.
AB  - Cattle could be exposed to the agent of chronic wasting disease (CWD) through
      contact with infected farmed or free-ranging cervids or exposure to contaminated
      premises. The purpose of the current study was to assess the potential for CWD
      derived from elk to transmit to cattle after intracranial inoculation. Calves (n
      = 14) were inoculated with brain homogenate derived from elk with CWD to
      determine the potential for transmission and to define the clinicopathologic
      features of disease. Cattle were necropsied if clinical signs occurred or at the
      end of the study (49 months postinoculation; MPI). Clinical signs of poor
      appetite, weight loss, circling, and bruxism occurred in 2 cattle (14%) at 16 and
      17 MPI, respectively. Accumulation of abnormal prion protein (PrP(Sc)) occurred
      in only the 2 clinically affected cattle and was confined to the central nervous
      system, with the most prominent immunoreactivity in midbrain, brainstem, and
      hippocampus with lesser immunoreactivity in the cervical spinal cord. The rate of
      transmission was lower than in cattle inoculated with CWD derived from mule deer
      (38%) or white-tailed deer (86%). Additional studies are required to fully assess
      the potential for cattle to develop CWD through a more natural route of exposure,
      but a low rate of transmission after intracranial inoculation suggests that risk
      of transmission through other routes is low. A critical finding is that if CWD
      did transmit to exposed cattle, currently used diagnostic techniques would detect
      and differentiate it from other prion diseases in cattle based on absence of
      spongiform change, distinct pattern of PrP(Sc) deposition, and unique molecular
      profile.

PMID- 22991390
TI  - Rickets: case series and diagnostic review of hypovitaminosis D in swine.
AB  - Rickets can be attributed to nutritional, genetic, hormonal, or toxic
      disturbances and is classified as a metabolic bone disease. Rickets is most often
      associated with inappropriate dietary levels of calcium, phosphorus, and/or
      vitamin D. During a 27-month period (January 2010 through March 2012), the Iowa
      State University Veterinary Diagnostic Laboratory investigated causes of sudden,
      unexpected death and lameness in growing pigs throughout the Midwestern United
      States. Clinical observations from 17 growing pig cases included weakness,
      lameness, reluctance to move, muscle fasciculations and/or tremors, tetany, and
      death. Ribs were weak, soft, and bent prior to breaking; rachitic lesions were
      apparent at costochondral junctions in multiple cases. Acute and/or chronic bone
      fractures were also noted in multiple bones. Failure of endochondral
      ossification, expanded physes, infractions, thin trabeculae, and increased
      osteoclasts were noted microscopically. Decreased bone ash and serum 25(OH)D(3),
      combined with clinical and microscopic evaluation, confirmed a diagnosis of
      vitamin D-dependent rickets in all cases. In 3 cases, disease was linked to a
      specific nutrient supplier that ultimately resulted in a voluntary feed recall;
      however, most cases in the current investigation were not associated with a
      particular feed company. The present report describes vitamin D-associated
      rickets and its importance as a potential cause of weakness, lameness, muscle
      fasciculations, recumbency or sudden unexpected death in swine, and describes
      appropriate samples and tests for disease diagnosis.

PMID- 22991391
TI  - Ten years of Interactive CardioVascular and Thoracic Surgery.

PMID- 22991392
TI  - eComment. Titanium devices in children.

PMID- 22991393
TI  - eComment. A pocket-sized imaging device during a minimally invasive pleural
      biopsy.

PMID- 22991394
TI  - eComment. The number of sternal wires influences sternal wound outcome.

PMID- 22991395
TI  - eComment. Postoperative delirium in cardiac surgery.

PMID- 22991396
TI  - eComment. Recombinant activated factor VII in pediatric cardiac surgery:
      possibilities and limitations.

PMID- 22991397
TI  - eComment. Enteral nutrition following oesophagectomy for oesophageal carcinoma 3
      July 2012.

PMID- 22991398
TI  - eComment. Surgery to treat atrial fibrillation: which technique is the best?

PMID- 22991399
TI  - eComment. Bipolar radiofrequency ablation for atrial fibrillation during
      concomitant cardiac surgery.

PMID- 22991400
TI  - eComment. Late presentation of thoracic textiloma.

PMID- 22991401
TI  - eComment. Unusual presentation of acute aortic dissection.

PMID- 22991403
TI  - The atria are fibrillating: does it matter to the resynchronized ventricles?

PMID- 22991404
TI  - Mineralocorticoid receptor antagonists and mortality in heart failure with
      concurrent atrial fibrillation.

PMID- 22991406
TI  - Lost in translation: examining patient and physician perceptions of implantable
      cardioverter-defibrillator deactivation discussions.

PMID- 22991407
TI  - Left ventricular noncompaction cardiomyopathy and aortopathy in a patient with
      recessive dystrophic epidermolysis bullosa.

PMID- 22991405
TI  - PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in
      Diastolic Heart Failure (RELAX) trial: rationale and design.

PMID- 22991410
TI  - Sudden cardiac death in adult congenital heart disease.
AB  - BACKGROUND: Sudden cardiac death (SCD) is a major cause of mortality in adults
      with congenital heart disease (CHD). The aim of this study was to determine the
      adult CHD population at risk of SCD and the clinical parameters associated with
      SCD. METHODS AND RESULTS: We performed a multicenter case-control study. Patients
      who died suddenly as a result of proven or presumed arrhythmia were included
      (cases). For each case, 2 controls matched on diagnosis, type of surgical
      intervention, age, and gender were included. From 3 databases including 25 790
      adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%)
      died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying
      cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the
      SCD cases, respectively. Clinical variables associated with SCD were
      supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI],
      1.5-7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4;
      95% CI, 1.1-10.4; P=0.034), moderate to severe subpulmonary ventricular
      dysfunction (OR, 3.4; 95% CI, 1.1-10.2; P=0.030), increased QRS duration (OR,
      1.34 [per 10-ms increase]; 95% CI, 1.10-1.34; P=0.008), and QT dispersion (OR,
      1.22 [per 10-ms increase]; 95% CI, 1.22-1.48; P=0.008). CONCLUSIONS: The clinical
      parameters found to be associated with SCD in adults with a broad spectrum of
      CHD, including systemic right ventricles, are similar to those in ischemic heart
      disease. Moreover, even those patients with mild cardiac lesions are potentially
      at risk for SCD. This highlights the need for further prospective studies as well
      as vigilant ongoing follow-up of the adult with CHD.

PMID- 22991412
TI  - The role of adipokines in beta-cell failure of type 2 diabetes.
AB  - beta-Cell failure coupled with insulin resistance is a key factor in the
      development of type 2 diabetes. Changes in circulating levels of adipokines,
      factors released from adipose tissue, form a significant link between excessive
      adiposity in obesity and both aforementioned factors. In this review, we consider
      the published evidence for the role of individual adipokines on the function,
      proliferation, death and failure of beta-cells, focusing on those reported to
      have the most significant effects (leptin, adiponectin, tumour necrosis factor
      alpha, resistin, visfatin, dipeptidyl peptidase IV and apelin). It is apparent
      that some adipokines have beneficial effects whereas others have detrimental
      properties; the overall contribution to beta-cell failure of changed
      concentrations of adipokines in the blood of obese pre-diabetic subjects will be
      highly dependent on the balance between these effects and the interactions
      between the adipokines, which act on the beta-cell via a number of intersecting
      intracellular signalling pathways. We emphasise the importance, and comparative
      dearth, of studies into the combined effects of adipokines on beta-cells.

PMID- 22991411
TI  - Cytokinesis microtubule organisers at a glance.

PMID- 22991413
TI  - ColoGuidePro: a prognostic 7-gene expression signature for stage III colorectal
      cancer patients.
AB  - PURPOSE: Improved prognostic stratification of patients with stage II and III
      colorectal cancer is warranted for postoperative clinical decision making. This
      study was conducted to develop a clinically feasible and robust prognostic
      classifier for these patients independent of adjuvant treatment. EXPERIMENTAL
      DESIGN: Global gene expression profiles from altogether 387 stage II and III
      colorectal cancer tissue samples from three independent patient series were
      included in the study. ColoGuidePro, a seven-gene prognostic classifier, was
      developed from a selected Norwegian learning series (n = 95; no adjuvant
      treatment) using lasso-penalized multivariate survival modeling with cross
      validation. RESULTS: The expression signature significantly stratified patients
      in a consecutive Norwegian test series, in which patients were treated according
      to current standards [HR, 2.9 (1.1-7.5); P = 0.03; n = 77] and an external
      validation series [HR, 3.7 (2.0-6.8); P < 0.001; n = 215] according to survival.
      ColoGuidePro was also an independent predictor of prognosis in multivariate
      models including tumor stage in both series (HR, >= 3.1; P <= 0.03). In the
      validation series, which consisted of patients from other populations (United
      States and Australia), 5-year relapse-free survival was significantly predicted
      for stage III patients only (P < 0.001; n = 107). Here, prognostic stratification
      was independent of adjuvant treatment (P = 0.001). CONCLUSIONS: We present
      ColoGuidePro, a prognostic classifier developed for patients with stage II and
      III colorectal cancer. The test is suitable for transfer to clinical use and has
      best prognostic prediction potential for stage III patients.

PMID- 22991415
TI  - MRI-based liver iron content predicts for nonrelapse mortality in MDS and AML
      patients undergoing allogeneic stem cell transplantation.
AB  - PURPOSE: Retrospective, surrogate marker-based studies have found inconsistent
      associations between systemic iron overload (SIO) and adverse outcome in patients
      undergoing allogeneic stem cell transplantation (allo-SCT). As a consequence, the
      impact of SIO in this context remains under debate. The aim of this study was to
      test whether the objective pretransplant quantification of liver-iron content
      (LIC) by magnetic resonance imaging (MRI) could circumvent these limitations and
      conclusively define the prognostic relevance of SIO. EXPERIMENTAL DESIGN: The
      correlation between pretransplant LIC and surrogate parameters as well as the
      impact of SIO on posttransplant outcome was assessed within an observational
      study of patients (n = 88) with either myelodysplastic syndrome (MDS) or acute
      myeloid leukemia (AML) undergoing allo-SCT. RESULTS: Ferritin levels of 1,000
      ng/mL or more provided only poor specificity (31.8%) for predicting elevated LIC
      (>=125 MUmol/g) and even higher thresholds (>=2,500 ng/mL) lacked an association
      with nonrelapse mortality (NRM). In contrast, LIC 125 MUmol/g or more was a
      significant risk factor for NRM in uni- and multivariate analysis (HR = 2.98; P =
      0.016). Multivariate Cox-regression further showed that LIC 125 MUmol/g or more
      was associated with a decreased overall survival (HR = 2.24, P = 0.038), whereas
      ferritin or transfusion burden were not. CONCLUSIONS: SIO reflected by LIC is an
      independent negative prognostic factor for posttransplant outcome in patients
      with AML and MDS undergoing allo-SCT. Therefore, MRI-based LIC, and not
      interference-prone serum markers such as ferritin, should be preferred for
      pretransplant risk stratification and patient selection in future clinical
      trials.

PMID- 22991414
TI  - Clinical significance of the genetic landscape of pancreatic cancer and
      implications for identification of potential long-term survivors.
AB  - PURPOSE: Genetic alterations of KRAS, CDKN2A, TP53, and SMAD4 are the most
      frequent events in pancreatic cancer. We determined the extent to which these 4
      alterations are coexistent in the same carcinoma, and their impact on patient
      outcome. EXPERIMENTAL DESIGN: Pancreatic cancer patients who underwent an autopsy
      were studied (n = 79). Matched primary and metastasis tissues were evaluated for
      intragenic mutations in KRAS, CDKN2A, and TP53 and immunolabeled for CDKN2A,
      TP53, and SMAD4 protein products. The number of altered driver genes in each
      carcinoma was correlated to clinicopathologic features. Kaplan-Meier estimates
      were used to determine median disease free and overall survival, and a Cox
      proportional hazards model used to compare risk factors. RESULTS: The number of
      genetically altered driver genes in a carcinoma was variable, with only 29
      patients (37%) having an alteration in all 4 genes analyzed. The number of
      altered driver genes was significantly correlated with disease free survival (P =
      0.008), overall survival (P = 0.041), and metastatic burden at autopsy (P =
      0.002). On multivariate analysis, the number of driver gene alterations in a
      pancreatic carcinoma remained independently associated with overall survival (P =
      0.046). Carcinomas with only 1 to 2 driver alterations were enriched for those
      patients with the longest survival (median 23 months, range 1 to 53).
      CONCLUSIONS: Determinations of the status of the 4 major driver genes in
      pancreatic cancer, and specifically the extent to which they are coexistent in an
      individual patients cancer, provides distinct information regarding disease
      progression and survival that is independent of clinical stage and treatment
      status.

PMID- 22991416
TI  - Identification of contractile P2Y1, P2Y6, and P2Y12 receptors in rat
      intrapulmonary artery using selective ligands.
AB  - ATP and UDP constrict rat intrapulmonary arteries, but which receptors mediate
      these actions is unclear. Here, we used selective agonists and antagonists, along
      with measurements of P2Y receptor expression, to characterize the receptor
      subtypes involved. Isometric tension was recorded from endothelium-denuded rat
      intrapulmonary artery rings (i.d. 200-500 MUm) mounted on a wire myograph.
      Expression of P2Y receptor subtype expression was determined by using reverse
      transcription-polymerase chain reaction with receptor-specific oligonucleotide
      primers. The selective P2Y(1) agonist (N)-methanocarba-2-methylthioadenosine-5'-O
      diphosphate (MRS2365) induced small, concentration-dependent contractions that
      were inhibited by the P2Y(1) antagonist N(6)-methyl-2'-deoxyadenosine-3',5'
      bisphosphate (MRS2179). Contractions evoked by ATP were unaffected by MRS2179,
      but inhibited by approximately one-third by the P2Y(12) antagonist N(6)-(2
      methylthiomethyl)-2-(3,3,3-trifluoropropylthio)dichloro-methylene ATP (AR
      C69931MX). Combined blockade of P2X1 and P2Y(12) receptors virtually abolished
      the response to ATP. ADP also evoked contractions that were abolished by AR
      C69931MX. The selective P2Y(6) receptor agonist 3-(2-oxo-2-phenylethyl)-UDP (PSB
      0474) evoked concentration-dependent contractions and was approximately three
      times more potent than UDP, but the P2Y(14) agonist UDP-glucose had no effect.
      Contractions evoked by UDP were inhibited by the P2Y(6) receptor antagonist N,N'
      1,4-butanediylbis-N'-(3-isothiocyanatophenyl)thiourea (MRS2578), but not the
      cysteinyl leukotriene 1 (CysL(1)) antagonist 3-(3-(2-(7-chloro-2
      quinolinyl)ethenyl)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)thiopropanoic
      acid (MK571). Higher concentrations of MRS2578 inhibited contractions to KCl, so
      they were not studied further. mRNA for P2Y(1), P2Y(6), and P2Y(12) receptors was
      identified. Our working model is that P2Y(12) and P2X1 receptors are present in
      rat intrapulmonary arteries and together mediate ATP-induced vasoconstriction.
      Contractile P2Y(6), but not P2Y(14) or CysLT(1), receptors are also present and
      are a major site through which UDP evokes constriction.

PMID- 22991418
TI  - Loss of N-cadherin from the endothelium causes stromal edema and epithelial
      dysgenesis in the mouse cornea.
AB  - PURPOSE: We analyzed the role of N-cadherin in maintaining proper architecture
      and function of corneal endothelium. METHODS: To achieve specific removal of N
      cadherin from corneal endothelium, we bred mice carrying a floxed N-cadherin gene
      with those expressing the Cre-recombinase gene under the control of P0 promoter.
      The corneal structure was analyzed by immunostaining for cell junction proteins
      as well as by electron microscopy. The apoptotic status was assessed by TUNEL
      staining. The permeability of corneal endothelium was evaluated using fluorescein
      dye. RESULTS: Removal of endothelial N-cadherin led to the appearance of opacity
      in the adult corneas. All corneal layers exhibited histological defects: The
      apical junctional complex (AJC) in corneal endothelium was disorganized, losing
      the continuity in tight junctions. Collagen fibrils were rearranged in the
      stroma. The corneal epithelium showed decreased thickness and TUNEL staining
      revealed increased central areas of apoptosis. Fluorescein dye injection in the
      anterior chamber confirmed an increased permeability of the endothelial layer.
      Developmental analysis indicated that, although N-cadherin was lost during
      embryonic stages, the AJC was maintained normally until early postnatal stages,
      probably due to the presence of other cadherins at these developmental stages.
      The junctional defects in endothelial cells, however, became obvious by postnatal
      day 21 (P21), although stromal and epithelial phenotypes were clearly detectable
      only in the adult eyes. CONCLUSIONS: N-cadherin is essential for maintaining
      proper structure of corneal endothelial AJCs from late postnatal to adult stages.
      Its ablation leads to increased endothelial permeability and corneal edema in
      mature eyes.

PMID- 22991417
TI  - Gamma-irradiation reduces the allogenicity of donor corneas.
AB  - PURPOSE: To evaluate the utility and allogenicity of gamma-irradiated corneal
      allografts. METHODS: Corneal buttons were harvested from C57BL/6 mice and
      decellularized with gamma irradiation. Cell viability was assessed using TUNEL
      and viability/cytotoxicity assays. Orthotopic penetrating keratoplasty was
      performed using irradiated or nonirradiated (freshly excised) C57BL/6 donor
      grafts and BALB/c or C57BL/6 recipients. Graft opacity was assessed over an 8
      week period and graft survival was evaluated using Kaplan-Meier survival curves.
      Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were
      performed to evaluate T-cell alloreactivity. Real-time PCR was used to
      investigate the corneal expression of potentially pathogenic T-helper 1, 2, and
      17 cell-associated cytokines. RESULTS: Corneal cells were devitalized by gamma
      irradiation as evidenced by widespread cellular apoptosis and plasma membrane
      disruption. Nonirradiated allograft and isograft rates of survival were superior
      to irradiated allograft and isograft rates of survival (P < 0.001). Mixed
      lymphocyte reactions demonstrated that T-cells from irradiated allograft
      recipients did not exhibit a secondary alloimmune response (P < 0.001). Delayed
      type hypersensitivity assays demonstrated that irradiated allografts did not
      elicit an alloreactive delayed-type hypersensitivity response in graft recipients
      (P <= 0.01). The corneal expression of T-helper 1, 2, and 17 cell-associated
      cytokines was significantly lower in failed irradiated allografts than rejected
      nonirradiated allografts (P <= 0.001). CONCLUSIONS: Gamma-irradiated corneas
      failed to remain optically clear following murine penetrating keratoplasty;
      however, gamma irradiation reduced the allogenicity of these corneas, potentially
      supporting their use in procedures such as anterior lamellar keratoplasty or
      keratoprosthesis implantation.

PMID- 22991419
TI  - Comparison of LASIK and surface ablation by using propensity score analysis: a
      multicenter study in Korea.
AB  - PURPOSE: We compared the 3-year outcomes with regard to efficacy, stability, and
      safety of LASIK and surface ablation performed at multiple centers in Korea.
      METHODS: The charts of 5109 eyes that underwent LASIK or surface ablation,
      including LASEK, epi-LASIK, and photorefractive keratectomy (PRK), at multiple
      centers between 2002 and 2005 were reviewed. Of these, 577 LASIK-treated eyes and
      577 propensity score-matched surface-ablated eyes were included in this cohort
      study. A standardized case report form (CRF) was completed based on a review of
      the 3-year follow-up chart. The CRF included the preoperative, surgical, and
      postoperative data for the refractive error, uncorrected visual acuity (UCVA),
      best spectacle-corrected visual acuity (BSCVA), IOP, corneal thickness,
      keratometry, corneal topography, Schirmer test, and tear breakup time (TBUT).
      RESULTS: The efficacy index calculated after 3 years and the postoperative
      spherical equivalents measured at 3 months or 3 years did not differ between the
      LASIK and surface ablation groups. Although myopic regression was observed in the
      surface ablation group through postoperative years 1 and 2, this difference did
      not affect the visual acuity significantly. Surface ablation did carry a higher
      cumulative incidence of corneal haze. CONCLUSIONS: LASIK and surface ablation
      produced similar postoperative visual efficacy after corneal healing. The outcome
      predictability did not differ between the 2 groups, but myopic regression was
      observed more frequently in the surface ablation group. Corneal haze after
      surface ablation is much more common than reported previously.

PMID- 22991420
TI  - Genetic characterization and susceptibility for sarcoidosis in Japanese patients:
      risk factors of BTNL2 gene polymorphisms and HLA class II alleles.
AB  - PURPOSE: Sarcoidosis is a heterogeneous and multisystem granulomatous disorder.
      The etiology still is uncertain, but the disease currently is thought to be
      triggered by various genetic as well as environmental factors. Recently, an
      association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located
      in close proximity to the HLA-DRB1 gene was reported. The purpose of our study
      was to verify the relationship between BTNL2 and HLA risk alleles for the
      susceptibility to sarcoidosis, and to assess whether the BTNL2 association is
      independent of the HLA risk alleles. METHODS: In our study, 11 single nucleotide
      polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304,
      rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional
      rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were
      genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy
      Japanese control subjects. RESULTS: In the patient group, the HLA-DRB1*08:03 (P =
      6.15 * 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 * 10(-6),
      OR = 1.84) were associated with disease susceptibility. Upon stratification
      analysis in search for a synergistic effect given the extensive linkage
      disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results
      suggested that the risk-bearing allele of these two loci interact negatively. No
      significant differences were observed in allele frequencies for alleles in
      patients with ocular and other systemic sarcoidosis. CONCLUSIONS: Our studies
      implicated that the HLA-DRB1 allele is a major contributing genetic factor in the
      development of sarcoidosis in Japan. However, further studies are needed to
      verify how HLA or BTNL2 alleles confer the disease phenotype, severity of
      sarcoidosis.

PMID- 22991421
TI  - Systematic reviews of studies quantifying the accuracy of diagnostic tests and
      markers.
AB  - Systematic reviews of diagnostic accuracy studies allow calculation of pooled
      estimates of accuracy with increased precision and examination of differences in
      accuracy between tests or subgroups of studies. Recently, several advances have
      been made in the methods used in performing systematic reviews of diagnostic test
      accuracy studies, most notably in how to assess the methodological quality of
      primary diagnostic test accuracy studies by use of QUADAS-2 (Quality Assessment
      of Diagnostic Accuracy Studies 2) instrument and how to develop sound statistical
      models for metaanalysis of the paired measures of test accuracy (bivariate
      metaregression model of sensitivity and specificity). This article provides an
      overview of the different steps within a diagnostic systematic review and
      highlights these advances, illustrated with empirical data. The potential
      benefits of some recent developments in the areas of network metaanalysis and
      individual patient data metaanalysis for diagnostic tests are also discussed.

PMID- 22991422
TI  - I see the light! And I see it again and again!

PMID- 22991423
TI  - Adaptive Bayesian analysis of serum creatinine as a marker for drug-induced renal
      impairment in an early-phase clinical trial.
AB  - BACKGROUND: A concern with using creatinine for the identification of drug
      induced renal impairment is that small changes in serum creatinine (SCr) that
      frequently are perceived as measurement bias or imprecision translate into
      important changes in the glomerular filtration rate. Important drug-generated
      changes in creatinine are difficult to detect because they are frequently
      observed within the reference interval. The design of a crossover drug protocol
      is an opportunity to use study participants as their own control to identify
      these small but important changes. METHODS: Twenty individuals participating in a
      phase I clinical trial were evaluated for SCr changes beyond those expected for
      biological variation according to individual Z scores derived from an adaptive
      Bayesian model. After 2 screening tests, participants were administered either
      drug (n = 11) or placebo (n = 9) during the first dosing interval. A washout
      period followed, and drug was then administered to the group that initially
      received placebo, and vice versa (10 visits total per participant). RESULTS:
      Although all creatinine values fell within the reference interval, 8 participants
      individually showed increased concentrations (Z scores >2.33). These 8
      participants were confirmed at unblinding to have received the drug in the
      identified dosing period, with 1 exception. CONCLUSIONS: The ability to identify
      a drug effect on an individual-participant basis in early-phase studies permits
      drug developers to recognize issues early in development and rapidly engage in
      risk-benefit analysis. These results suggest that SCr monitoring is able to
      detect early kidney dysfunction when individual-based reference intervals are
      used.

PMID- 22991424
TI  - Characterization of fluoroquinolone and cephalosporin resistance mechanisms in
      Enterobacteriaceae isolated in a Dutch teaching hospital reveals the presence of
      an Escherichia coli ST131 clone with a specific mutation in parE.
AB  - OBJECTIVES: To characterize the mechanisms of fluoroquinolone and cephalosporin
      resistance in Enterobacteriaceae from a Dutch teaching hospital in 2008. METHODS:
      We sequenced gyrA, gyrB, parC and parE. The presence of plasmid-encoded genes
      qnrA, qnrB, qnrS, aac(6')-Ib, qepA, bla(TEM), bla(SHV,) bla(OXA), bla(CTX-M) and
      bla(AmpC) was studied by PCR. Escherichia coli isolates were further
      characterized by AFLP and multilocus sequence typing (MLST). RESULTS: In total,
      49 E. coli, 16 Klebsiella pneumoniae and 3 Enterobacter cloacae isolates were
      investigated. Mutations in gyrA were found in all E. coli isolates. Forty-five
      (92%) E. coli isolates carried at least one point mutation in parC. Most E. coli
      isolates (59%) also carried mutations in parE, of which I529L was the most
      prevalent. I529L was unequivocally associated with E. coli sequence type (ST)
      131. This single-nucleotide polymorphism (SNP) was later also found in eight out
      of nine ST131 strains from another collection. Twenty-nine E. coli isolates
      carried extended-spectrum beta-lactamase (ESBL) genes, predominantly bla(CTX-M
      15). In E. coli, aac(6')-Ib-cr was the predominant plasmid-mediated resistance
      mechanism, whereas in K. pneumoniae qnr genes were found mostly. In K. pneumoniae
      isolates, qnr and aac(6')-Ib-cr co-occurred with ESBL genes (n = 13; bla(CTX-M)
      and bla(SHV)) and/or bla(AmpC) (n = 3; bla(DHA-1)). CONCLUSIONS: E. coli ST131
      was the predominant clone, which accumulated a high number of chromosomal
      mutations. The I529L SNP in parE was a signature of most, but not all, ST131
      strains. In contrast to E. coli, fluoroquinolone resistance mechanisms were
      predominantly plasmid-encoded in K. pneumoniae.

PMID- 22991425
TI  - In vivo antibiofilm effect of cerium, chitosan and hamamelitannin against usual
      agents of catheter-related bloodstream infections.
AB  - OBJECTIVES: Catheter-related bloodstream infections (CRBSIs) are common
      healthcare-associated infections associated with increased morbidity and medical
      costs. Antiseptic- and antibiotic-coated central venous catheters (CVCs) have
      been proposed to reduce the incidence of CRBSIs, with variable success. The aim
      of this study was to determine the in vivo antibiofilm activity of biocompatible
      and inexpensive compounds, such as cerium nitrate, chitosan and hamamelitannin,
      against usual agents of CRBSIs. METHODS: The antibiofilm effect of cerium
      nitrate, chitosan and hamamelitannin was tested against Staphylococcus
      epidermidis, Staphylococcus aureus, Acinetobacter baumannii and Candida albicans
      in a mouse foreign body infection model, using polyurethane catheter segments.
      Biofilm formation was assessed with a crystal violet assay to quantify the total
      biomass, with a tetrazolium reduction assay to quantify the metabolic activity
      and with scanning electron microscopy. RESULTS: At subinhibitory concentrations,
      cerium nitrate significantly reduced biofilm formation by C. albicans, chitosan
      significantly decreased biofilm formation by S. epidermidis and C. albicans, and
      hamamelitannin significantly inhibited all bacterial biofilms. DISCUSSION: The in
      vivo antibiofilm effect of cerium nitrate against C. albicans and of chitosan
      against C. albicans and S. epidermidis, at subinhibitory concentrations, makes
      them promising alternatives to coat CVCs. Moreover, the microbicidal effect on a
      wider range of CVC colonizers was previously reported in vitro for both
      compounds, at higher concentrations. For all bacterial strains, the highest in
      vivo antibiofilm efficacy was achieved with hamamelitannin. For A. baumannii,
      this is the first report of in vivo inhibition.

PMID- 22991426
TI  - "We communicated that way for a reason": language practices and language
      ideologies among hearing adults whose parents are deaf.
AB  - Families with deaf parents and hearing children are often bilingual and bimodal,
      with both a spoken language and a signed one in regular use among family members.
      When interviewed, 13 American hearing adults with deaf parents reported widely
      varying language practices, sign language abilities, and social affiliations with
      Deaf and Hearing communities. Despite this variation, the interviewees' moral
      judgments of their own and others' communicative behavior suggest that these
      adults share a language ideology concerning the obligation of all family members
      to expend effort to overcome potential communication barriers. To our knowledge,
      such a language ideology is not similarly pervasive among spoken-language
      bilingual families, raising the question of whether there is something unique
      about family bimodal bilingualism that imposes different rights and
      responsibilities on family members than spoken-language family bilingualism does.
      This ideology unites an otherwise diverse group of interviewees, where each one
      preemptively denied being a "typical CODA [children of deaf adult]."

PMID- 22991427
TI  - An intervention for early mathematical success: outcomes from the hybrid version
      of the Building Math Readiness Parents as Partners (MRPP) project.
AB  - The Building Math Readiness in Young Deaf/Hard-of- Hearing Children: Parents as
      Partners (MRPP) Project works with parents to increase the understanding of
      foundational mathematics concepts in their preschool deaf/hard-of-hearing (d/hh)
      children in preparation for formal mathematics education. A multiple-case/single
      unit case study incorporating descriptive statistics and grounded theory analysis
      was conducted on the hybrid version of the intervention. Results showed
      productive changes in parental behaviors indicating a possible positive effect on
      parent knowledge, recognition, and mediation of early matthematics concepts with
      their young d/hh children.

PMID- 22991428
TI  - Binding of aldolase and glyceraldehyde-3-phosphate dehydrogenase to the
      cytoplasmic tails of Plasmodium falciparum merozoite duffy binding-like and
      reticulocyte homology ligands.
AB  - Invasion of erythrocytes by Plasmodium falciparum requires a connection between
      the cytoplasmic tail of the parasite's ligands for its erythrocyte receptors and
      the actin-myosin motor of the parasite. For the thromobospondin-related anonymous
      protein (TRAP) ligand on Plasmodium sporozoites, aldolase forms this connection
      and requires tryptophan and negatively charged amino acids in the ligand's
      cytoplasmic tail. Because of the importance of the Duffy binding-like (DBL) and
      the reticulocyte homology (RH) ligand families in erythrocyte binding and
      merozoite invasion, we characterized the ability of their cytoplasmic tails to
      bind aldolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), both of which
      bind actin. We tested the binding of the cytoplasmic peptides of the two ligand
      families to aldolase and GAPDH. Only the cytoplasmic peptides of some RH ligands
      showed strong binding to aldolase, and the binding depended on the presence of an
      aromatic amino acid (phenylalanine or tyrosine), rather than tryptophan, in the
      context of negatively charged amino acids. The binding was confirmed by surface
      plasmon resonance analysis and was found to represent affinity similar to that
      seen with TRAP. An X-ray crystal structure of aldolase at 2.5 A in the presence
      of RH2b peptide suggested that the binding site location was near the TRAP
      binding site. GAPDH bound to some of the cytoplasmic tails of certain RH and DBL
      ligands in an aromatic amino acid-dependent manner. Thus, the connection between
      Plasmodium merozoite ligands and erythrocyte receptors and the actin motor can be
      achieved through the activity of either aldolase or GAPDH by mechanisms that do
      not require tryptophan but, rather, other aromatic amino acids. IMPORTANCE The
      invasion of the Plasmodium merozoite into erythrocytes is a critical element in
      malaria pathogenesis. It is important to understand the molecular details of this
      process, as this machinery can be a target for both vaccine and drug development.
      In Plasmodium sporozoites and Toxoplasma tachyzoites, invasion involves a
      glycolytic enzyme aldolase, linking the cytoplasmic tail domains of the parasite
      ligands to the actin-myosin motor that drives invasion. This binding requires a
      tryptophan that cannot be replaced by other aromatic residues. Here we show that
      aldolase binds the cytoplasmic tails of some P. falciparum merozoite erythrocyte
      binding ligands but that the binding involves aromatic residues other than
      tryptophan. The biological relevance of aldolase binding to cytoplasmic tails of
      parasite ligands in invasion is demonstrated by our observation that RH2b but not
      RH2a binds to aldolase and, as previously shown, that RH2b but not RH2a is
      required for P. falciparum invasion of erythrocytes.

PMID- 22991429
TI  - Streamlining and core genome conservation among highly divergent members of the
      SAR11 clade.
AB  - SAR11 is an ancient and diverse clade of heterotrophic bacteria that are abundant
      throughout the world's oceans, where they play a major role in the ocean carbon
      cycle. Correlations between the phylogenetic branching order and spatiotemporal
      patterns in cell distributions from planktonic ocean environments indicate that
      SAR11 has evolved into perhaps a dozen or more specialized ecotypes that span
      evolutionary distances equivalent to a bacterial order. We isolated and sequenced
      genomes from diverse SAR11 cultures that represent three major lineages and
      encompass the full breadth of the clade. The new data expand observations about
      genome evolution and gene content that previously had been restricted to the
      SAR11 Ia subclade, providing a much broader perspective on the clade's origins,
      evolution, and ecology. We found small genomes throughout the clade and a very
      high proportion of core genome genes (48 to 56%), indicating that small genome
      size is probably an ancestral characteristic. In their level of core genome
      conservation, the members of SAR11 are outliers, the most conserved free-living
      bacteria known. Shared features of the clade include low GC content, high gene
      synteny, a large hypervariable region bounded by rRNA genes, and low numbers of
      paralogs. Variation among the genomes included genes for phosphorus metabolism,
      glycolysis, and C1 metabolism, suggesting that adaptive specialization in
      nutrient resource utilization is important to niche partitioning and ecotype
      divergence within the clade. These data provide support for the conclusion that
      streamlining selection for efficient cell replication in the planktonic habitat
      has occurred throughout the evolution and diversification of this clade.
      IMPORTANCE The SAR11 clade is the most abundant group of marine microorganisms
      worldwide, making them key players in the global carbon cycle. Growing knowledge
      about their biochemistry and metabolism is leading to a more mechanistic
      understanding of organic carbon oxidation and sequestration in the oceans. The
      discovery of small genomes in SAR11 provided crucial support for the theory that
      streamlining selection can drive genome reduction in low-nutrient environments.
      Study of isolates in culture revealed atypical organic nutrient requirements that
      can be attributed to genome reduction, such as conditional auxotrophy for glycine
      and its precursors, a requirement for reduced sulfur compounds, and evidence for
      widespread cycling of C1 compounds in marine environments. However, understanding
      the genetic variation and distribution of such pathways and characteristics like
      streamlining throughout the group has required the isolation and genome
      sequencing of diverse SAR11 representatives, an analysis of which we provide
      here.

PMID- 22991430
TI  - A multicenter blinded analysis indicates no association between chronic fatigue
      syndrome/myalgic encephalomyelitis and either xenotropic murine leukemia virus
      related virus or polytropic murine leukemia virus.
AB  - The disabling disorder known as chronic fatigue syndrome or myalgic
      encephalomyelitis (CFS/ME) has been linked in two independent studies to
      infection with xenotropic murine leukemia virus-related virus (XMRV) and
      polytropic murine leukemia virus (pMLV). Although the associations were not
      confirmed in subsequent studies by other investigators, patients continue to
      question the consensus of the scientific community in rejecting the validity of
      the association. Here we report blinded analysis of peripheral blood from a
      rigorously characterized, geographically diverse population of 147 patients with
      CFS/ME and 146 healthy subjects by the investigators describing the original
      association. This analysis reveals no evidence of either XMRV or pMLV infection.
      IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated
      prevalence of 42/10,000 in the United States, with annual direct medical costs of
      $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic
      murine leukemia virus) in blood of subjects with this disorder report that this
      association is not confirmed in a blinded analysis of samples from rigorously
      characterized subjects. The increasing frequency with which molecular methods are
      used for pathogen discovery poses new challenges to public health and support of
      science. It is imperative that strategies be developed to rapidly and coherently
      address discoveries so that they can be carried forward for translation to
      clinical medicine or abandoned to focus resource investment more productively.
      Our study provides a paradigm for pathogen dediscovery that may be helpful to
      others working in this field.

PMID- 22991433
TI  - An excitingly predictable 'omic future.

PMID- 22991431
TI  - Transcriptome changes induced by Epstein-Barr virus LMP1 and LMP2A in transgenic
      lymphocytes and lymphoma.
AB  - Latent membrane protein 1 (LMP1) and LMP2A affect cell growth in both epithelial
      cells and lymphocytes. In this study, the effects on cellular gene expression
      were determined by microarray analysis of transgenic mice expressing LMP1, LMP2A,
      or both using the immunoglobulin heavy chain promoter and enhancer. Large
      differential changes were detected, indicating that LMP1 and LMP2A can both
      potently affect host gene transcription, inducing distinct transcriptional
      profiles. Seventy percent of the changes detected in LMP1/2A doubly transgenic
      lymphocytes were also modulated by LMP1 or LMP2A alone. These common and unique
      expression changes indicate that the combined effects of LMP1 and LMP2A may be
      additive, synergistic, or inhibitory. Using significant pathway analysis, the
      expression changes detected in LMP1, LMP2A, and LMP1/2A transgenic B lymphocytes
      were predicted to commonly target cancer and inflammatory pathways. Additionally,
      using the correlation coefficient to calculate the regulation of known c-Rel and
      Stat3 transcriptional targets, both were found to be enhanced in LMP1 lymphocytes
      and lymphomas, and a selection of Stat3 targets was further evaluated and
      confirmed using quantitative reverse transcription-PCR (RT-PCR). Analyses of the
      effects on cell growth and viability revealed that LMP2A transgenic lymphocytes
      had the greatest enhanced viability in vitro; however, doubly transgenic
      lymphocytes (LMP1/2A) did not have enhanced survival in culture and these mice
      were similar to negative littermates. These findings indicate that the combined
      expression of LMP1 and LMP2A has potentially different biological outcomes than
      when the two proteins are expressed individually. IMPORTANCE The Epstein-Barr
      virus proteins latent membrane protein 1 (LMP1) and LMP2A have potent effects on
      cell growth. In transgenic mice that express these proteins in B lymphocytes, the
      cell growth and survival properties are also affected. LMP1 transgenic mice have
      increased development of lymphoma, and the LMP1 lymphocytes have increased
      viability in culture. LMP2A transgenic lymphocytes have altered B cell
      development and enhanced survival. In this study, analysis of the cellular gene
      expression changes in transgenic LMP1 and LMP2A lymphocytes and LMP1 lymphomas
      revealed that both transgenes individually and in combination affected pathways
      important for the development of cancer and inflammation. Importantly, the
      combined expression of the two proteins had unique effects on cellular expression
      and cell viability. This is the first study to look at the combined effects of
      LMP1 and LMP2A on global changes in host gene expression.

PMID- 22991434
TI  - Plant developmental biologists meet on stairways in Matera.
AB  - The third EMBO Conference on Plant Molecular Biology, which focused on 'Plant
      development and environmental interactions', was held in May 2012 in Matera,
      Italy. Here, we review some of the topics and themes that emerged from the
      various contributions; namely, steering technologies, transcriptional networks
      and hormonal regulation, small RNAs, cell and tissue polarity, environmental
      control and natural variation. We intend to provide the reader who might have
      missed this remarkable event with a glimpse of the recent progress made in this
      blossoming research field.

PMID- 22991436
TI  - Ectodomain shedding and ADAMs in development.
AB  - Proteolytic enzymes belonging to the A Disintegin And Metalloproteinase (ADAM)
      family are able to cleave transmembrane proteins close to the cell surface, in a
      process referred to as ectodomain shedding. Substrates for ADAMs include growth
      factors, cytokines, chemokines and adhesion molecules, and, as such, many ADAM
      proteins play crucial roles in cell-cell adhesion, extracellular and
      intracellular signaling, cell differentiation and cell proliferation. In this
      Review, we summarize the fascinating roles of ADAMs in embryonic and adult tissue
      development in both vertebrates and invertebrates.

PMID- 22991435
TI  - Stomatal development: a plant's perspective on cell polarity, cell fate
      transitions and intercellular communication.
AB  - The plant stomatal lineage manifests features common to many developmental
      contexts: precursor cells are chosen from an initially equivalent field of cells,
      undergo asymmetric and self-renewing divisions, communicate among themselves and
      respond to information from a distance. As we review here, the experimental
      accessibility of these epidermal lineages, particularly in Arabidopsis, has made
      stomata a conceptual and technical framework for the study of cell fate, stem
      cells, and cell polarity in plants.

PMID- 22991437
TI  - Differential requirements for beta-catenin during mouse development.
AB  - Embryogenesis relies on the precise interplay of signaling cascades to activate
      tissue-specific differentiation programs. An important player in these
      morphogenetic processes is beta-catenin, which is a central component of adherens
      junctions and canonical Wnt signaling. Lack of beta-catenin is lethal before
      gastrulation, but mice heterozygous for beta-catenin (Ctnnb1) develop as wild
      type. Here, we confine beta-catenin amounts below the heterozygous expression
      level to study the functional consequences for development. We generate embryonic
      stem (ES) cells and embryos expressing beta-catenin only from the ubiquitously
      active ROSA26 promoter and thereby limit beta-catenin expression to ~12.5%
      (ROSA26(beta/+)) or ~25% (ROSA26(beta/beta)) of wild-type levels. ROSA26(beta/+)
      is sufficient to maintain ES cell morphology and pluripotent characteristics, but
      is insufficient to activate canonical target genes upon Wnt stimulation. This Wnt
      signaling deficiency is incompletely restored in ROSA26(beta/beta) ES cells. We
      conclude that even very low beta-catenin levels are able to sustain cell
      adhesion, but not Wnt signaling. During development, ROSA26(beta/beta) as well as
      ROSA26(beta/+) partially rescues the knockout phenotype, yet proper gastrulation
      is absent. These embryos differentiate according to the neural default
      hypothesis, indicating that gastrulation depends on high beta-catenin levels.
      Strikingly, if ROSA26(beta/+) or ROSA26(beta/beta) is first activated after
      gastrulation, subsequent development correlates with the dosage of beta-catenin.
      Moreover, molecular evidence indicates that the amount of beta-catenin controls
      the induction of specific Wnt target genes. In conclusion, by restricting its
      expression we determine the level of beta-catenin required for adhesion or
      pluripotency and during different morphogenetic events.

PMID- 22991438
TI  - Developmental fate and lineage commitment of singled mouse blastomeres.
AB  - The inside-outside model has been invoked to explain cell-fate specification of
      the pre-implantation mammalian embryo. Here, we investigate whether cell-cell
      interaction can influence the fate specification of embryonic blastomeres by
      sequentially separating the blastomeres in two-cell stage mouse embryos and
      continuing separation after each cell division throughout pre-implantation
      development. This procedure eliminates information provided by cell-cell
      interaction and cell positioning. Gene expression profiles, polarity protein
      localization and functional tests of these separated blastomeres reveal that cell
      interactions, through cell position, influence the fate of the blastomere.
      Blastomeres, in the absence of cell contact and inner-outer positional
      information, have a unique pattern of gene expression that is characteristic of
      neither inner cell mass nor trophectoderm, but overall they have a tendency
      towards a 'trophectoderm-like' gene expression pattern and preferentially
      contribute to the trophectoderm lineage.

PMID- 22991440
TI  - Redefining the structure of the hair follicle by 3D clonal analysis.
AB  - The hair follicle (HF) is a multi-tissue mini-organ that self-renews
      periodically. However, the cellular organisation of this much-studied model is
      not fully understood. The structures of the outer layer and of the bulb, which
      ensures HF growth, have not been completely established. To clarify these points,
      we have conducted in vivo clonal analyses with 3D imaging in mice. The upper two
      thirds of the HF outer layer consists of two clonally unrelated groups of cells
      that exhibit different modes of growth. They correspond to the basal outer root
      sheath (ORS) and the companion layer (Cp). The basal ORS has an unusual
      anisotropic mode of growth from a suprabulbar zone, which we named the privileged
      proliferation zone. The Cp has a stem/transient-amplifying mode of growth and is
      shown to be an HF internal structure. Furthermore, we describe an additional
      element, the bulb outer layer, which is contiguous and shares markers (e.g. Lgr5)
      with the basal ORS but is formed by a separate lineage that belongs neither to
      the ORS nor Cp lineage. It represents a novel element with proximal cells that
      are contiguous with the germinative layer in the bulb. In reference to its shape
      and position we named it the lower proximal cup (LPC). These clonal hierarchies
      reveal a novel model of HF organisation and growth based on two major entities:
      the basal ORS and the LPC plus the seven internal layers.

PMID- 22991439
TI  - The P granule component PGL-1 promotes the localization and silencing activity of
      the PUF protein FBF-2 in germline stem cells.
AB  - In the C. elegans germline, maintenance of undifferentiated stem cells depends on
      the PUF family RNA-binding proteins FBF-1 and FBF-2. FBF-1 and FBF-2 are 89%
      identical and are required redundantly to silence the expression of mRNAs that
      promote meiosis. Here we show that, despite their extensive sequence similarity,
      FBF-1 and FBF-2 have different effects on target mRNAs. FBF-1 promotes the
      degradation and/or transport of meiotic mRNAs out of the stem cell region,
      whereas FBF-2 prevents translation. FBF-2 activity depends on the P granule
      component PGL-1. PGL-1 is required to localize FBF-2 to perinuclear P granules
      and for efficient binding of FBF-2 to its mRNA targets. We conclude that multiple
      regulatory mechanisms converge on meiotic RNAs to ensure silencing in germline
      stem cells. Our findings also support the view that P granules facilitate mRNA
      silencing by providing an environment in which translational repressors can
      encounter their mRNA targets immediately upon exit from the nucleus.

PMID- 22991441
TI  - Delta-like 1 and lateral inhibition during hair cell formation in the chicken
      inner ear: evidence against cis-inhibition.
AB  - The formation of the salt-and-pepper mosaic of hair cells and supporting cells in
      the sensory epithelia of the inner ear is regulated by Notch signalling and
      lateral inhibition, but the dynamics of this process and precise mode of action
      of delta-like 1 (Dll1) in this context are unclear. Here, we transfected the
      chicken inner ear with a fluorescent reporter that includes elements of the
      mammalian Hes5 promoter to monitor Notch activity in the developing sensory
      patches. The Hes5 reporter was active in proliferating cells and supporting
      cells, and Dll1 expression was highest in prospective hair cells with low levels
      of Notch activity, which occasionally contacted more differentiated hair cells.
      To investigate Dll1 functions we used constructs in which Dll1 expression was
      either constitutive, regulated by the Hes5 promoter, or induced by doxycycline.
      In support of the standard lateral inhibition model, both continuous and Hes5
      regulated expression of Dll1 promoted hair cell differentiation cell-autonomously
      (in cis) and inhibited hair cell formation in trans. However, some hair cells
      formed despite contacting Dll1-overexpressing cells, suggesting that some
      progenitor cells are insensitive to lateral inhibition. This is not due to the
      cis-inhibition of Notch activity by Dll1 itself, as induction of Dll1 did not
      cell-autonomously reduce the activity of the Hes5 reporter in progenitor and
      supporting cells. Altogether, our results show that Dll1 functions primarily in
      trans to regulate hair cell production but also that additional mechanisms
      operate downstream of lateral inhibition to eliminate patterning errors in the
      sensory epithelia of the inner ear.

PMID- 22991442
TI  - Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the
      inner ear.
AB  - Vangl2 is one of the central proteins controlling the establishment of planar
      cell polarity in multiple tissues of different species. Previous studies suggest
      that the localization of the Vangl2 protein to specific intracellular
      microdomains is crucial for its function. However, the molecular mechanisms that
      control Vangl2 trafficking within a cell are largely unknown. Here, we identify
      Gipc1 (GAIP C-terminus interacting protein 1) as a new interactor for Vangl2, and
      we show that a myosin VI-Gipc1 protein complex can regulate Vangl2 traffic in
      heterologous cells. Furthermore, we show that in the cochlea of MyoVI mutant
      mice, Vangl2 presence at the membrane is increased, and that a disruption of
      Gipc1 function in hair cells leads to maturation defects, including defects in
      hair bundle orientation and integrity. Finally, stimulated emission depletion
      microscopy and overexpression of GFP-Vangl2 show an enrichment of Vangl2 on the
      supporting cell side, adjacent to the proximal membrane of hair cells.
      Altogether, these results indicate a broad role for Gipc1 in the development of
      both stereociliary bundles and cell polarization, and suggest that the strong
      asymmetry of Vangl2 observed in early postnatal cochlear epithelium is mostly a
      'tissue' polarity readout.

PMID- 22991444
TI  - Transcriptional regulatory mechanisms underlying the GABAergic neuron fate in
      different diencephalic prosomeres.
AB  - Diverse mechanisms regulate development of GABAergic neurons in different regions
      of the central nervous system. We have addressed the roles of a proneural gene,
      Ascl1, and a postmitotic selector gene, Gata2, in the differentiation of
      GABAergic neuron subpopulations in three diencephalic prosomeres: prethalamus
      (P3), thalamus (P2) and pretectum (P1). Although the different proliferative
      progenitor populations of GABAergic neurons commonly express Ascl1, they have
      distinct requirements for it in promotion of cell-cycle exit and GABAergic neuron
      identity. Subsequently, Gata2 is activated as postmitotic GABAergic precursors
      are born. In P1, Gata2 regulates the neurotransmitter identity by promoting
      GABAergic and inhibiting glutamatergic neuron differentiation. Interestingly,
      Gata2 defines instead the subtype of GABAergic neurons in the rostral thalamus
      (pTh-R), which is a subpopulation of P2. Without Gata2, the GABAergic precursors
      born in the pTh-R fail to activate subtype-specific markers, but start to express
      genes typical of GABAergic precursors in the neighbouring P3 domain. Thus, our
      results demonstrate diverse mechanisms regulating differentiation of GABAergic
      neuron subpopulations and suggest a role for Gata2 as a selector gene of both
      GABAergic neuron neurotransmitter and prosomere subtype identities in the
      developing diencephalon. Our results demonstrate for the first time that neuronal
      identities between distinct prosomeres can still be transformed in postmitotic
      neuronal precursors.

PMID- 22991443
TI  - Autonomy in specification of primordial germ cells and their passive
      translocation in the sea urchin.
AB  - The process of germ line determination involves many conserved genes, yet is
      highly variable. Echinoderms are positioned at the base of Deuterostomia and are
      crucial to understanding these evolutionary transitions, yet the mechanism of
      germ line specification is not known in any member of the phyla. Here we
      demonstrate that small micromeres (SMics), which are formed at the fifth cell
      division of the sea urchin embryo, illustrate many typical features of primordial
      germ cell (PGC) specification. SMics autonomously express germ line genes in
      isolated culture, including selective Vasa protein accumulation and
      transcriptional activation of nanos; their descendants are passively displaced
      towards the animal pole by secondary mesenchyme cells and the elongating
      archenteron during gastrulation; Cadherin (G form) has an important role in their
      development and clustering phenotype; and a left/right integration into the
      future adult anlagen appears to be controlled by a late developmental mechanism.
      These results suggest that sea urchin SMics share many more characteristics
      typical of PGCs than previously thought, and imply a more widely conserved system
      of germ line development among metazoans.

PMID- 22991445
TI  - Essential roles of the histone methyltransferase ESET in the epigenetic control
      of neural progenitor cells during development.
AB  - In the developing brain, neural progenitor cells switch differentiation
      competency by changing gene expression profiles that are governed partly by
      epigenetic control, such as histone modification, although the precise mechanism
      is unknown. Here we found that ESET (Setdb1), a histone H3 Lys9 (H3K9)
      methyltransferase, is highly expressed at early stages of mouse brain development
      but downregulated over time, and that ablation of ESET leads to decreased H3K9
      trimethylation and the misregulation of genes, resulting in severe brain defects
      and early lethality. In the mutant brain, endogenous retrotransposons were
      derepressed and non-neural gene expression was activated. Furthermore, early
      neurogenesis was severely impaired, whereas astrocyte formation was enhanced. We
      conclude that there is an epigenetic role of ESET in the temporal and tissue
      specific gene expression that results in proper control of brain development.

PMID- 22991446
TI  - Evidence for karyoplasmic homeostasis during endoreduplication and a ploidy
      dependent increase in gene transcription during tomato fruit growth.
AB  - Endopolyploidy is a widespread process that corresponds to the amplification of
      the genome in the absence of mitosis. In tomato, very high ploidy levels (up to
      256C) are reached during fruit development, concomitant with very large cell
      sizes. Using cellular approaches (fluorescence and electron microscopy) we
      provide a structural analysis of endoreduplicated nuclei at the level of
      chromatin and nucleolar organisation, nuclear shape and relationship with other
      cellular organelles such as mitochondria. We demonstrate that endopolyploidy in
      pericarp leads to the formation of polytene chromosomes and markedly affects
      nuclear structure. Nuclei manifest a complex shape, with numerous deep grooves
      that are filled with mitochondria, affording a fairly constant ratio between
      nuclear surface and nuclear volume. We provide the first direct evidence that
      endopolyploidy plays a role in increased transcription of rRNA and mRNA on a per
      nucleus basis. Overall, our results provide quantitative evidence in favour of
      the karyoplasmic theory and show that endoreduplication is associated with
      complex cellular organisation during tomato fruit development.

PMID- 22991447
TI  - Targeted disruption of inducible nitric oxide synthase protects against aging, S
      nitrosation, and insulin resistance in muscle of male mice.
AB  - Accumulating evidence has demonstrated that S-nitrosation of proteins plays a
      critical role in several human diseases. Here, we explored the role of inducible
      nitric oxide synthase (iNOS) in the S-nitrosation of proteins involved in the
      early steps of the insulin-signaling pathway and insulin resistance in the
      skeletal muscle of aged mice. Aging increased iNOS expression and S-nitrosation
      of major proteins involved in insulin signaling, thereby reducing insulin
      sensitivity in skeletal muscle. Conversely, aged iNOS-null mice were protected
      from S-nitrosation-induced insulin resistance. Moreover, pharmacological
      treatment with an iNOS inhibitor and acute exercise reduced iNOS-induced S
      nitrosation and increased insulin sensitivity in the muscle of aged animals.
      These findings indicate that the insulin resistance observed in aged mice is
      mainly mediated through the S-nitrosation of the insulin-signaling pathway.

PMID- 22991448
TI  - Frequency and severity of the dawn phenomenon in type 2 diabetes: relationship to
      age.
AB  - OBJECTIVE: To know whether age has an independent effect on the dawn phenomenon
      in noninsulin-using type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-one
      individuals with type 2 diabetes were matched for HbA(1c) and divided by age into
      three subgroups of 27 individuals (1: >=70 years; 2: 60-69 years; and 3: <=59
      years). All underwent ambulatory continuous glucose monitoring for quantifying
      the dawn phenomenon (i.e., the absolute [?G, mg/dL] or relative [?G%] increments
      from nocturnal nadirs to prebreakfast time points). RESULTS: HbA(1c) levels and
      24-h glycemic profiles were similar across the three groups. Glucose increments
      (mean +/- SEM) were identical in the three groups: ?G (mg/dL), 22.0 +/- 4.7 (1),
      21.3 +/- 3.6 (2), and 18.0 +/- 3.6 (3) and deltaG (%), 19.9 +/- 4.9 (1), 21.6 +/-
      4.4 (2), and 17.6 +/- 4.2 (3). Using the most common definition (?G >10 mg/dL),
      the prevalence of the dawn phenomenon was 52, 70, and 59% in groups 1, 2, and 3,
      respectively. CONCLUSIONS: The dawn phenomenon is present in the elderly.

PMID- 22991449
TI  - Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and
      pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact
      on pain, polysomnographic sleep, daytime functioning, and quality of life.
AB  - OBJECTIVE: Chronic diabetic peripheral neuropathic pain (DPNP) is difficult to
      treat, with treatment regimens often inadequate at controlling pain and limited
      by side effects and drug tolerance. Secondary parameters, such as quality of
      sleep and mood, may also be important for successful DPNP management. The
      objectives of this study were to compare the analgesic efficacy of pregabalin,
      amitriptyline, and duloxetine, and their effect on polysomnographic sleep,
      daytime functioning, and quality of life in patients with DPNP. RESEARCH DESIGN
      AND METHODS: This was a double-blind, randomized, parallel group investigation of
      type 1 and 2 diabetic subjects with DPNP. Each treatment group had a single
      blind, 8-day, placebo run-in followed by 14 days of lower-dose and 14 days of
      higher-dose medication. At the end of each dose titration period, subjective
      pain, sleep, and daytime functioning were assessed during a 2-day residential
      period. RESULTS: All medications reduced pain when compared with placebo, but no
      one treatment was superior to any other. For sleep, pregabalin improved sleep
      continuity (P < 0.001), whereas duloxetine increased wake and reduced total sleep
      time (P < 0.01 and P < 0.001). Despite negative effects on sleep, duloxetine
      enhanced central nervous system arousal and performance on sensory motor tasks.
      There were no significant safety findings; however, there was a significantly
      higher number of adverse events in the pregabalin treatment group. CONCLUSIONS:
      There was no significant difference in analgesic efficacy between amitriptyline,
      duloxetine, and pregabalin. However, there were significant differences in the
      secondary parameters, which may be of relevance when deciding the optimal
      treatment for DPNP.

PMID- 22991450
TI  - Impact of the hypoxia-inducible factor-1 alpha (HIF1A) Pro582Ser polymorphism on
      diabetes nephropathy.
AB  - OBJECTIVE: Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We
      have investigated in this study the effect of hypoxia-inducible factor 1 alpha
      subunit (HIF1A) genetic polymorphisms on the development of DN. RESEARCH DESIGN
      AND METHODS: In 1,165 American type 1 diabetic patients with and without DN
      selected from the Genetics of Kidneys in Diabetes (GoKinD) study, the HIF1A
      genetic polymorphisms were genotyped with TaqMan allelic discrimination. The
      regulation of HIF-1alpha in the kidneys of diabetic mice was appreciated by
      immunohistochemistry, and the effect HIF1A Pro582Ser polymorphism on HIF-1alpha
      sensitivity to glucose was evaluated in vitro. RESULTS: We identified a
      protective association between HIF1A Pro582Ser polymorphism and DN in male
      subjects. We also provided mechanistic insights that HIF-1alpha is repressed in
      the medulla of diabetic mice despite hypoxia and that Pro582Ser polymorphism
      confers less sensitivity to the inhibitory effect of glucose during a hypoxic
      challenge. CONCLUSIONS: The current study demonstrates for the first time that
      HIF1A Pro582Ser polymorphism has an effect on DN, possibly by conferring a
      relative resistance to the repressive effect of glucose on HIF-1alpha.

PMID- 22991452
TI  - Mate pair sequencing of whole-genome-amplified DNA following laser capture
      microdissection of prostate cancer.
AB  - High-throughput next-generation sequencing provides a revolutionary platform to
      unravel the precise DNA aberrations concealed within subgroups of tumour cells.
      However, in many instances, the limited number of cells makes the application of
      this technology in tumour heterogeneity studies a challenge. In order to address
      these limitations, we present a novel methodology to partner laser capture
      microdissection (LCM) with sequencing platforms, through a whole-genome
      amplification (WGA) protocol performed in situ directly on LCM engrafted cells.
      We further adapted current Illumina mate pair (MP) sequencing protocols to the
      input of WGA DNA and used this technology to investigate large genomic
      rearrangements in adjacent Gleason Pattern 3 and 4 prostate tumours separately
      collected by LCM. Sequencing data predicted genome coverage and depths similar to
      unamplified genomic DNA, with limited repetition and bias predicted in WGA
      protocols. Mapping algorithms developed in our laboratory predicted high
      confidence rearrangements and selected events each demonstrated the predicted
      fusion junctions upon validation. Rearrangements were additionally confirmed in
      unamplified tissue and evaluated in adjacent benign-appearing tissues. A detailed
      understanding of gene fusions that characterize cancer will be critical in the
      development of biomarkers to predict the clinical outcome. The described
      methodology provides a mechanism of efficiently defining these events in limited
      pure populations of tumour tissue, aiding in the derivation of genomic
      aberrations that initiate cancer and drive cancer progression.

PMID- 22991451
TI  - Identification of novel genes selectively expressed in the follicle-associated
      epithelium from the meta-analysis of transcriptomics data from multiple mouse
      cell and tissue populations.
AB  - The follicle-associated epithelium (FAE) overlying the Peyer's patches and the
      microfold cells (M cells) within it are important sites of antigen transcytosis
      across the intestinal epithelium. Using a meta-analysis approach, we identified a
      transcriptional signature that distinguished the FAE from a large collection of
      mouse cells and tissues. A co-expressed cluster of 21 FAE-specific genes was
      identified, and the analysis of the transcription factor binding site motifs in
      their promoter regions indicated that these genes shared an underlying
      transcriptional programme. This cluster contained known FAE- (Anxa10, Ccl20,
      Psg18 and Ubd) and M-cell-specific (Gp2) genes, suggesting that the others were
      novel FAE-specific genes. Some of these novel candidate genes were expressed
      highly by the FAE and M cells (Calcb, Ces3b, Clca2 and Gjb2), and others only by
      the FAE (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). We
      also identified a subset of novel FAE-related genes that were induced in the
      intestinal epithelium after receptor activator of nuclear factor (NF)-kappaB
      ligand stimulation. These included Mfge8 which was specific to FAE enterocytes.
      This study provides new insight into the FAE transcriptome. Further
      characterization of the candidate genes identified here will aid the
      identification of novel regulators of cell function in the FAE.

PMID- 22991453
TI  - Regurgitation after Edwards SAPIEN valve implantation: truly paravalvular or
      'supra-skirtal'?

PMID- 22991454
TI  - Impact of ESC/ACCF/AHA/WHF universal definition of myocardial infarction on
      mortality at 10 years.
AB  - AIMS: Redefinition of myocardial infarction (MI) based on specific cardiac
      troponins (cTn) was universally accepted in 2007. The new definition has been
      widely discussed for including a large spectrum of quantitative myocardial
      necrosis and their clinical implications remain under debate. Our aim was to
      assess the impact of the universal definition of MI on mortality at 10 years.
      METHODS AND RESULTS: We studied 676 consecutive patients (Pts) admitted to our
      intensive cardiac care unit for acute coronary syndrome (ACS) between January
      1999 and December 2000. We calculated the relative risk of the total death at 10
      years adjusted with the Cox proportional hazards model, between the presence and
      absence of MI following different definitions: (1), typical symptoms and
      persistent ST-segment elevation or left bundle branch block (ST-segment elevation
      definition); (2), typical symptoms and CK-MB activity rise and/or fall >ULN (old
      definition); and (3), typical symptoms and cTn I rise and/or fall >99th
      percentile (universal definition). The total mortality at 10 years was 23.8%. The
      proportion of Pts with AMI was 33.6% for ST-segment elevation definition, 55.8%
      for old definition, and 70.1% for universal definition. The adjusted hazard ratio
      of death at 10 years between the presence and absence of AMI was 0.71 (95%
      confidence interval (CI): 0.46-1.08; P = 0.11) for ST-segment elevation
      definition, 0.84 (95% CI: 0.55-1.27; P = 0.40) for old definition, and 1.58 (95%
      CI: 1.07-2.40; P = 0.03) for universal definition. Patients submitted to
      myocardial revascularization during the initial hospital stay (72%) presented a
      significantly lower mortality at 10 years, compared with patients not
      revascularized (adjusted hazard ratio: 0.63, 95% CI: 0.44-0.91; P = 0.014).
      CONCLUSIONS: In a population with the entire spectrum of ACSs, the universal
      definition of MI increased this diagnosis by one-quarter and was an independent
      predictor of mortality at 10 years. Furthermore, myocardial revascularization was
      associated with a significantly lower mortality at 10 years.

PMID- 22991455
TI  - Impact of thrombus aspiration during primary percutaneous coronary intervention
      on mortality in ST-segment elevation myocardial infarction.
AB  - AIMS: To assess the impact of thrombus aspiration during primary percutaneous
      coronary intervention (PPCI) on the mortality of patients with ST-elevation
      myocardial infarction (STEMI) patients. METHODS AND RESULTS: Retrospective
      analysis of prospectively collected data on 2567 consecutive PPCI-treated STEMI
      patients between 2008 and 2011. Cox proportional hazard models and multiple
      logistic regression analysis were used to adjust for known covariates.
      Thrombectomy was performed in 1095 patients (42.7%). Post-PPCI thrombolysis in
      myocardial infarction 3 flow was more frequently achieved in the thrombectomy
      group [adjusted odds ratio (OR); 1.92, 95% confidence interval (CI): 1.34-2.76, P
      = 0.0004]. Overall in-hospital and longer term (mean follow-up 9.9 months)
      mortality rates were 4.5 and 9.0%, respectively. Thrombectomy was associated with
      a significant reduction in in-hospital (adjusted OR: 0.51, 95% CI: 0.29-0.93, P =
      0.027) and longer term mortality [adjusted hazard ratio (HR): 0.69, 95% CI: 0.48
      0.96, P = 0.028]. With propensity weighting, the adjusted HR for longer term
      mortality for thrombectomy was 0.43 (95% CI: 0.19-0.97; P = 0.042). The
      association between thrombectomy and reduced longer term mortality was only
      significant in those with a total ischaemic time <=180min (P = 0.001) but not in
      patients with a total ischaemic time >180min (P = 0.99). CONCLUSION: This study
      of real-world, unselected STEMI patients demonstrates that thrombus aspiration
      during PPCI is associated with a significant reduction in mortality, especially
      in those with a short total ischaemic time. These findings support the use of
      thrombectomy during PPCI in this group of patients.

PMID- 22991456
TI  - An unexpected cause of postoperative right heart failure.

PMID- 22991457
TI  - Mechanism for reduced pericardial adhesion formation in hypercholesterolemic
      swine supplemented with alcohol.
AB  - OBJECTIVE: Previous experiments in Yorkshire swine demonstrated significantly
      fewer pericardial adhesions and intramyocardial collagen deposition at
      reoperative sternotomy in animals supplemented with vodka but not with red wine.
      The purpose of this experiment was to determine a mechanism for adhesion
      reduction. METHODS: Twenty-seven male Yorkshire swine were fed a high-cholesterol
      diet to simulate conditions of coronary artery disease followed by the surgical
      placement of an ameroid constrictor to the left circumflex coronary artery to
      induce chronic ischaemia. Postoperatively, control pigs continued their high
      fat/cholesterol diet alone, whereas the two experimental groups had diets
      supplemented with either red wine or vodka for 7 weeks followed by reoperative
      sternotomy and cardiac harvest. RESULTS: The expression of related adhesion focal
      tyrosine kinase (RAFTK) and caspase 3 in the sodium dodecyl sulphate (SDS)
      soluble myocardial fraction was significantly higher only in the vodka
      supplemented group. In the more soluble fraction, the expression of caspase 3,
      cleaved caspase 3 and caspase 9 was lower in both the vodka and red wine
      treatment groups. CONCLUSIONS: In the SDS-soluble lysate fraction, likely
      representing the transmembrane/cell-extracellular matrix (ECM), a significant
      increase in RAFTK and caspase 3 expression was seen only in the vodka-treated
      animals, which may explain why this group demonstrated significantly fewer
      pericardial adhesions. Caspase expression/signalling was not increased in the
      more soluble myocardial lysate, suggesting that the increased apoptotic
      signalling was specific to the epicardial-ECM.

PMID- 22991458
TI  - The role of T-tubes in the management of airway stenosis.
AB  - OBJECTIVES: When the T-tube is inserted as a temporary stent, it is unclear
      whether keeping it longer in place has any benefit on the outcome. METHODS: Among
      1738 patients with airway stenosis (1996-2011), 134 underwent T-tube placement
      (mean duration = 14.3 months); temporarily while waiting for an appropriate time
      for surgery in 53 (Group 1), as an adjunct after a complex laryngotracheal
      resection in 27 (Group 2), after surgical failure in 43 (Group 3) and permanently
      in 11 unresectable strictures (Group 4). A logistic regression model was used for
      statistical analysis. RESULTS: Seventy percent of patients were males (age = 33.6
      +/- 17 years). The main cause was postintubation/post-tracheostomy stenosis in
      87% of patients. The stenosis (29.6 +/- 14 mm, 5-80 mm) was located in the
      subglottis in 33%, trachea in 47% and both in 20% of cases. To assess the effect
      of T-tubes on stabilizing the airway after decannulation, 50 patients who still
      had a T-tube at the end of follow-up or for <1.5 months were excluded. Of the
      remaining 84, 31.5, 91.5 and 32.5% of patients in Groups 1, 2 and 3 were stable
      at least 3 months after decannulation. Moreover, 70% of those who were
      decannulated at or before 6 months and 53.7% of those who were decannulated after
      6 months underwent another intervention (P = 0.17). The age, sex, cause, site of
      stenosis and even duration of T-tube insertion (P = 0.07) showed no significant
      effect on the decannulation outcome. CONCLUSIONS: Although it seems that keeping
      the T-tube in place for >6 months may increase the chance of successful
      decannulation, it was not confirmed in our study.

PMID- 22991459
TI  - Characterizing the mechanics of cultured cell monolayers.
AB  - One-cell-thick monolayers are the simplest tissues in multicellular organisms,
      yet they fulfill critical roles in development and normal physiology. In early
      development, embryonic morphogenesis results largely from monolayer rearrangement
      and deformation due to internally generated forces. Later, monolayers act as
      physical barriers separating the internal environment from the exterior and must
      withstand externally applied forces. Though resisting and generating mechanical
      forces is an essential part of monolayer function, simple experimental methods to
      characterize monolayer mechanical properties are lacking. Here, we describe a
      system for tensile testing of freely suspended cultured monolayers that enables
      the examination of their mechanical behavior at multi-, uni-, and subcellular
      scales. Using this system, we provide measurements of monolayer elasticity and
      show that this is two orders of magnitude larger than the elasticity of their
      isolated cellular components. Monolayers could withstand more than a doubling in
      length before failing through rupture of intercellular junctions. Measurement of
      stress at fracture enabled a first estimation of the average force needed to
      separate cells within truly mature monolayers, approximately ninefold larger than
      measured in pairs of isolated cells. As in single cells, monolayer mechanical
      properties were strongly dependent on the integrity of the actin cytoskeleton,
      myosin, and intercellular adhesions interfacing adjacent cells. High
      magnification imaging revealed that keratin filaments became progressively
      stretched during extension, suggesting they participate in monolayer mechanics.
      This multiscale study of monolayer response to deformation enabled by our device
      provides the first quantitative investigation of the link between monolayer
      biology and mechanics.

PMID- 22991460
TI  - Engineering neonatal Fc receptor-mediated recycling and transcytosis in
      recombinant proteins by short terminal peptide extensions.
AB  - The importance of therapeutic recombinant proteins in medicine has led to a
      variety of tactics to increase their circulation time or to enable routes of
      administration other than injection. One clinically successful tactic to improve
      both protein circulation and delivery is to fuse the Fc domain of IgG to
      therapeutic proteins so that the resulting fusion proteins interact with the
      human neonatal Fc receptor (FcRn). As an alternative to grafting the high
      molecular weight Fc domain to therapeutic proteins, we have modified their N
      and/or C termini with a short peptide sequence that interacts with FcRn. Our
      strategy was motivated by results [Mezo AR, et al. (2008) Proc Natl Acad Sci USA
      105:2337-2342] that identified peptides that compete with human IgG for FcRn. The
      small size and simple structure of the FcRn-binding peptide (FcBP) allows for
      expression of FcBP fusion proteins in Escherichia coli and results in their pH
      dependent binding to FcRn with an affinity comparable to that of IgG. The FcBP
      fusion proteins are internalized, recycled, and transcytosed across cell
      monolayers that express FcRn. This strategy has the potential to improve protein
      transport across epithelial barriers, which could lead to noninvasive
      administration and also enable longer half-lives of therapeutic proteins.

PMID- 22991461
TI  - Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates
      conventional T cells from Foxp3+ regulatory T cells.
AB  - Several lines of evidence suggest nuclear factor of activated T-cells (NFAT) to
      control regulatory T cells: thymus-derived naturally occurring regulatory T cells
      (nTreg) depend on calcium signals, the Foxp3 gene harbors several NFAT binding
      sites, and the Foxp3 (Fork head box P3) protein interacts with NFAT. Therefore,
      we investigated the impact of NFAT on Foxp3 expression. Indeed, the generation of
      peripherally induced Treg (iTreg) by TGF-beta was highly dependent on NFAT
      expression because the ability of CD4(+) T cells to differentiate into iTreg
      diminished markedly with the number of NFAT family members missing. It can be
      concluded that the expression of Foxp3 in TGF-beta-induced iTreg depends on the
      threshold value of NFAT rather than on an individual member present. This is
      specific for iTreg development, because frequency of nTreg remained unaltered in
      mice lacking NFAT1, NFAT2, or NFAT4 alone or in combination. Different from
      expectation, however, the function of both nTreg and iTreg was independent on
      robust NFAT levels, reflected by less nuclear NFAT in nTreg and iTreg.
      Accordingly, absence of one or two NFAT members did not alter suppressor activity
      in vitro or during colitis and transplantation in vivo. This scenario emphasizes
      an inhibition of high NFAT activity as treatment for autoimmune diseases and in
      transplantation, selectively targeting the proinflammatory conventional T cells,
      while keeping Treg functional.

PMID- 22991462
TI  - Redox regulation of MAPK phosphatase 1 controls monocyte migration and macrophage
      recruitment.
AB  - Monocytic adhesion and chemotaxis are regulated by MAPK pathways, which in turn
      are controlled by redox-sensitive MAPK phosphatases (MKPs). We recently reported
      that metabolic disorders prime monocytes for enhanced recruitment into vascular
      lesions by increasing monocytes' responsiveness to chemoattractants. However, the
      molecular details of this proatherogenic mechanism were not known. Here we show
      that monocyte priming results in the S-glutathionylation and subsequent
      inactivation and degradation of MKP-1. Chronic exposure of human THP-1 monocytes
      to diabetic conditions resulted in the loss of MKP-1 protein levels, the
      hyperactivation of ERK and p38 in response to monocyte chemoattractant protein-1
      (MCP-1), and increased monocyte adhesion and chemotaxis. Knockdown of MKP-1
      mimicked the priming effects of metabolic stress, whereas MKP-1 overexpression
      blunted both MAPK activation and monocyte adhesion and migration induced by MCP
      1. Metabolic stress promoted the S-glutathionylation of MKP-1, targeting MKP-1
      for proteasomal degradation. Preventing MKP-1 S-glutathionylation in
      metabolically stressed monocytes by overexpressing glutaredoxin 1 protected MKP-1
      from degradation and normalized monocyte adhesion and chemotaxis in response to
      MCP-1. Blood monocytes isolated from diabetic mice showed a 55% reduction in MKP
      1 activity compared with nondiabetic mice. Hematopoietic MKP-1 deficiency in
      atherosclerosis-prone mice mimicked monocyte priming and dysfunction associated
      with metabolic disorders, increased monocyte chemotaxis in vivo, and accelerated
      atherosclerotic lesion formation. In conclusion, we identified MKP-1 as a central
      redox-sensitive regulator of monocyte adhesion and migration and showed that the
      loss of MKP-1 activity is a critical step in monocyte priming and the metabolic
      stress-induced conversion of blood monocytes into a proatherogenic phenotype.

PMID- 22991463
TI  - Functional transcriptomics of a migrating cell in Caenorhabditis elegans.
AB  - In both metazoan development and metastatic cancer, migrating cells must carry
      out a detailed, complex program of sensing cues, binding substrates, and moving
      their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a
      stereotyped migration that guides gonad organogenesis, occurs with precise
      timing, and requires the nuclear hormone receptor NHR-67. To better understand
      how this occurs, we performed RNA-seq of individually staged and dissected linker
      cells, comparing transcriptomes from linker cells of third-stage (L3) larvae,
      fourth-stage (L4) larvae, and nhr-67-RNAi-treated L4 larvae. We observed
      expression of 8,000-10,000 genes in the linker cell, 22-25% of which were up- or
      down-regulated 20-fold during development by NHR-67. Of genes that we tested by
      RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting
      that many NHR-67-dependent, linker cell-enriched genes play roles in this
      migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore
      potassium channels, which are required for normal linker-cell migration. We also
      found phenotypes for genes with human orthologs but no previously described
      migratory function. Our results provide an extensive catalog of genes that act in
      a migrating cell, identify unique molecular functions involved in nematode cell
      migration, and suggest similar functions in humans.

PMID- 22991464
TI  - Mitochondrial ribonuclease P structure provides insight into the evolution of
      catalytic strategies for precursor-tRNA 5' processing.
AB  - Ribonuclease P (RNase P) catalyzes the maturation of the 5' end of tRNA
      precursors. Typically these enzymes are ribonucleoproteins with a conserved RNA
      component responsible for catalysis. However, protein-only RNase P (PRORP)
      enzymes process precursor tRNAs in human mitochondria and in all tRNA-using
      compartments of Arabidopsis thaliana. PRORP enzymes are nuclear encoded and
      conserved among many eukaryotes, having evolved recently as yeast mitochondrial
      genomes encode an RNase P RNA. Here we report the crystal structure of PRORP1
      from A. thaliana at 1.75 A resolution, revealing a prototypical metallonuclease
      domain tethered to a pentatricopeptide repeat (PPR) domain by a structural zinc
      binding domain. The metallonuclease domain is a unique high-resolution structure
      of a Nedd4-BP1, YacP Nucleases (NYN) domain that is a member of the PIN domain
      like fold superfamily, including the FLAP nuclease family. The structural
      similarity between PRORP1 and the FLAP nuclease family suggests that they evolved
      from a common ancestor. Biochemical data reveal that conserved aspartate residues
      in PRORP1 are important for catalytic activity and metal binding and that the PPR
      domain also enhances activity, likely through an interaction with pre-tRNA. These
      results provide a foundation for understanding tRNA maturation in organelles.
      Furthermore, these studies allow for a molecular-level comparison of the
      catalytic strategies used by the only known naturally evolved protein and RNA
      based catalysts that perform the same biological function, pre-tRNA maturation,
      thereby providing insight into the differences between the prebiotic RNA world
      and the present protein-dominated world.

PMID- 22991465
TI  - Complications dawn for kinetochore regulation by Aurora.

PMID- 22991466
TI  - Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia
      coli as determined by whole-genome sequencing.
AB  - Knowledge of the rate and nature of spontaneous mutation is fundamental to
      understanding evolutionary and molecular processes. In this report, we analyze
      spontaneous mutations accumulated over thousands of generations by wild-type
      Escherichia coli and a derivative defective in mismatch repair (MMR), the primary
      pathway for correcting replication errors. The major conclusions are (i) the
      mutation rate of a wild-type E. coli strain is ~1 * 10(-3) per genome per
      generation; (ii) mutations in the wild-type strain have the expected mutational
      bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the
      absence of MMR; (iii) during replication, A:T > G:C transitions preferentially
      occur with A templating the lagging strand and T templating the leading strand,
      whereas G:C > A:T transitions preferentially occur with C templating the lagging
      strand and G templating the leading strand; (iv) there is a strong bias for
      transition mutations to occur at 5'ApC3'/3'TpG5' sites (where bases 5'A and 3'T
      are mutated) and, to a lesser extent, at 5'GpC3'/3'CpG5' sites (where bases 5'G
      and 3'C are mutated); (v) although the rate of small (<=4 nt) insertions and
      deletions is high at repeat sequences, these events occur at only 1/10th the
      genomic rate of base-pair substitutions. MMR activity is genetically regulated,
      and bacteria isolated from nature often lack MMR capacity, suggesting that
      modulation of MMR can be adaptive. Thus, comparing results from the wild-type and
      MMR-defective strains may lead to a deeper understanding of factors that
      determine mutation rates and spectra, how these factors may differ among
      organisms, and how they may be shaped by environmental conditions.

PMID- 22991467
TI  - Staphylococcal pathogenicity island interference with helper phage reproduction
      is a paradigm of molecular parasitism.
AB  - Staphylococcal pathogenicity islands (SaPIs) carry superantigen and resistance
      genes and are extremely widespread in Staphylococcus aureus and in other Gram
      positive bacteria. SaPIs represent a major source of intrageneric horizontal gene
      transfer and a stealth conduit for intergeneric gene transfer; they are phage
      satellites that exploit the life cycle of their temperate helper phages with
      elegant precision to enable their rapid replication and promiscuous spread. SaPIs
      also interfere with helper phage reproduction, blocking plaque formation, sharply
      reducing burst size and enhancing the survival of host cells following phage
      infection. Here, we show that SaPIs use several different strategies for phage
      interference, presumably the result of convergent evolution. One strategy, not
      described previously in the bacteriophage microcosm, involves a SaPI-encoded
      protein that directly and specifically interferes with phage DNA packaging by
      blocking the phage terminase small subunit. Another strategy involves
      interference with phage reproduction by diversion of the vast majority of virion
      proteins to the formation of SaPI-specific small infectious particles. Several
      SaPIs use both of these strategies, and at least one uses neither but possesses a
      third. Our studies illuminate a key feature of the evolutionary strategy of these
      mobile genetic elements, in addition to their carriage of important genes
      interference with helper phage reproduction, which could ensure their
      transferability and long-term persistence.

PMID- 22991468
TI  - Statistical connectivity provides a sufficient foundation for specific functional
      connectivity in neocortical neural microcircuits.
AB  - It is well-established that synapse formation involves highly selective
      chemospecific mechanisms, but how neuron arbors are positioned before synapse
      formation remains unclear. Using 3D reconstructions of 298 neocortical cells of
      different types (including nest basket, small basket, large basket, bitufted,
      pyramidal, and Martinotti cells), we constructed a structural model of a cortical
      microcircuit, in which cells of different types were independently and randomly
      placed. We compared the positions of physical appositions resulting from the
      incidental overlap of axonal and dendritic arbors in the model (statistical
      structural connectivity) with the positions of putative functional synapses
      (functional synaptic connectivity) in 90 synaptic connections reconstructed from
      cortical slice preparations. Overall, we found that statistical connectivity
      predicted an average of 74 +/- 2.7% (mean +/- SEM) synapse location distributions
      for nine types of cortical connections. This finding suggests that chemospecific
      attractive and repulsive mechanisms generally do not result in pairwise-specific
      connectivity. In some cases, however, the predicted distributions do not match
      precisely, indicating that chemospecific steering and aligning of the arbors may
      occur for some types of connections. This finding suggests that random alignment
      of axonal and dendritic arbors provides a sufficient foundation for specific
      functional connectivity to emerge in local neural microcircuits.

PMID- 22991469
TI  - A kinetic clutch governs religation by type IB topoisomerases and determines
      camptothecin sensitivity.
AB  - Type IB topoisomerases (Top1Bs) relax excessive DNA supercoiling associated with
      replication and transcription by catalyzing a transient nick in one strand to
      permit controlled rotation of the DNA about the intact strand. The natural
      compound camptothecin (CPT) and the cancer chemotherapeutics derived from it,
      irinotecan and topotecan, are highly specific inhibitors of human nuclear Top1B
      (nTop1). Previous work on vaccinia Top1B led to an elegant model that describes a
      straightforward dependence of rotation and religation on the torque caused by
      supercoiling. Here, we used a single-molecule DNA supercoil relaxation assay to
      measure the torque dependence of nTop1 and its inhibition by CPT. For comparison,
      we also examined mitochondrial Top1B and an N-terminal deletion mutant of nTop1.
      Despite substantial sequence homology in their core domains, nTop1 and
      mitochondrial Top1B exhibit dramatic differences in sensitivity to torque and
      CPT, with the N-terminal deletion mutant of nTop1 showing intermediate
      characteristics. In particular, nTop1 displays nearly torque-independent
      religation probability, distinguishing it from other Top1B enzymes studied to
      date. Kinetic modeling reveals a hitherto unobserved torque-independent
      transition linking the DNA rotation and religation phases of the enzymatic cycle.
      The parameters of this transition determine the torque sensitivity of religation
      and the efficiency of CPT binding. This "kinetic clutch" mechanism explains the
      molecular basis of CPT sensitivity and more generally provides a framework with
      which to interpret Top1B activity and inhibition.

PMID- 22991470
TI  - Engineering of blended nanoparticle platform for delivery of mitochondria-acting
      therapeutics.
AB  - Mitochondrial dysfunctions cause numerous human disorders. A platform technology
      based on biodegradable polymers for carrying bioactive molecules to the
      mitochondrial matrix could be of enormous potential benefit in treating
      mitochondrial diseases. Here we report a rationally designed mitochondria
      targeted polymeric nanoparticle (NP) system and its optimization for efficient
      delivery of various mitochondria-acting therapeutics by blending a targeted
      poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)
      triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA
      b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro
      screening of a library of charge- and size-varied NPs, and mitochondrial uptake
      was studied by qualitative and quantitative investigations of cytosolic and
      mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG
      TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD.
      The versatility of this platform was demonstrated by studying various
      mitochondria-acting therapeutics for different applications, including the
      mitochondria-targeting chemotherapeutics lonidamine and alpha-tocopheryl
      succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer's
      disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These
      biomolecules were loaded into blended NPs with high loading efficiencies.
      Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable
      improvement in the drug therapeutic index for cancer, Alzheimer's disease, and
      obesity compared with the nontargeted construct or the therapeutics in their free
      form. This work represents the potential of a single, programmable NP platform
      for the diagnosis and targeted delivery of therapeutics for mitochondrial
      dysfunction-related diseases.

PMID- 22991471
TI  - Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor,
      RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.
AB  - B cells and plasma cells possess distinct RNA processing environments that
      respectively promote the expression of membrane-associated Ig by B cells versus
      the secretion of Ig by plasma cells. Through a combination of transcriptional
      profiling and screening using a lentiviral short-hairpin RNA interference
      library, we show that both the splicing factor hnRNPLL and the transcription
      elongation factor ELL2 modulate the ratio of secreted versus membrane-encoding
      Ighg2b transcripts in MPC11 plasmacytoma cell lines. hnRNPLL and ELL2 are both
      highly expressed in primary plasma cells relative to B cells, but hnRNPLL binds
      Ighg2b mRNA transcripts and promotes an increase in levels of the membrane
      encoding Ighg2b isoform at the expense of the secreted Ighg2b isoform, whereas
      ELL2 counteracts this effect and drives Ig secretion by increasing the frequency
      of the secreted Ighg2b isoform. As in T cells, hnRNPLL also alters the splicing
      pattern of mRNA encoding the adhesion receptor CD44, promoting exon inclusion,
      and decreasing the overall level of CD44 expression. Further characterization of
      ELL2-dependent transcription by RNA-Seq revealed that ~12% of transcripts
      expressed by plasma cells were differentially processed because of the activities
      of ELL2, including B-cell maturation antigen BCMA, a receptor with a defined role
      in plasma cell survival. Taken together, our data identify hnRNPLL and ELL2 as
      regulators of pre-mRNA processing in plasma cells.

PMID- 22991473
TI  - Identification of a specific reprogramming-associated epigenetic signature in
      human induced pluripotent stem cells.
AB  - Generation of human induced pluripotent stem cells (hiPSCs) by the expression of
      specific transcription factors depends on successful epigenetic reprogramming to
      a pluripotent state. Although hiPSCs and human embryonic stem cells (hESCs)
      display a similar epigenome, recent reports demonstrated the persistence of
      specific epigenetic marks from the somatic cell type of origin and aberrant
      methylation patterns in hiPSCs. However, it remains unknown whether the use of
      different somatic cell sources, encompassing variable levels of selection
      pressure during reprogramming, influences the level of epigenetic aberrations in
      hiPSCs. In this work, we characterized the epigenomic integrity of 17 hiPSC lines
      derived from six different cell types with varied reprogramming efficiencies. We
      demonstrate that epigenetic aberrations are a general feature of the hiPSC state
      and are independent of the somatic cell source. Interestingly, we observe that
      the reprogramming efficiency of somatic cell lines inversely correlates with the
      amount of methylation change needed to acquire pluripotency. Additionally, we
      determine that both shared and line-specific epigenetic aberrations in hiPSCs can
      directly translate into changes in gene expression in both the pluripotent and
      differentiated states. Significantly, our analysis of different hiPSC lines from
      multiple cell types of origin allow us to identify a reprogramming-specific
      epigenetic signature comprised of nine aberrantly methylated genes that is able
      to segregate hESC and hiPSC lines regardless of the somatic cell source or
      differentiation state.

PMID- 22991475
TI  - Modeling the protection of photosynthesis.

PMID- 22991474
TI  - Interplay between electrical activity and bone morphogenetic protein signaling
      regulates spinal neuron differentiation.
AB  - A gradient of bone morphogenetic proteins (BMPs) along the dorsoventral axis of
      the spinal cord is necessary for the specification of dorsal neurons.
      Concurrently, a gradient of calcium-mediated electrical activity is present in
      the developing spinal cord but in an opposing ventrodorsal direction. Whether
      BMPs and electrical activity interact in embryonic spinal neurons remains
      unknown. We show that BMP decreases electrical activity by enhancing p38 MAPK
      mediated negative modulation of voltage-gated sodium channels. In turn,
      electrical activity affects the phosphorylation status and nuclear level of
      activated Smads, the canonical components of BMP signaling. This interaction
      between calcium spike activity and BMP signaling regulates the specification of
      the dorsal commissural spinal neuron phenotype. The present study identifies an
      unexpected interplay between BMPs and electrical activity that is critical for
      decoding the morphogen gradient during spinal neuron differentiation.

PMID- 22991476
TI  - Pyomyositis.

PMID- 22991477
TI  - Reporting of incorrect cause-of-death causal sequence on death certificates in
      the USA: using hypertension and diabetes as an educational illustration.
AB  - BACKGROUND: Little is known about the extent of reporting an incorrect cause-of
      death (COD) causal sequence on death certificates. OBJECTIVE: To determine the
      frequency of incorrect reporting of hypertension as cause of diabetes on death
      certificates in the USA. METHODS: Multiple-cause mortality files were used to
      identify death certificates which mentioned both hypertension and diabetes in the
      USA from 1985 to 2005. The frequency of reporting hypertension on the line below
      diabetes in part I of the death certificate was calculated. RESULTS: The
      percentage of cases in which both hypertension and diabetes were included in part
      I of the death certificate, in which hypertension was reported on the line below
      diabetes on the death certificate-that is, suggesting that hypertension was a
      cause of diabetes-increased from 15.5% in 1985 to 36.1% in 2000 and 38.2% in
      2005. CONCLUSIONS: The frequency of reporting of an incorrect COD causal sequence
      on death certificates in the USA has increased. Education, training and
      questioning the opinions of certifying physicians are needed to improve the
      quality of reporting of COD statements.

PMID- 22991478
TI  - Digital optical phase conjugation of fluorescence in turbid tissue.
AB  - We demonstrate a method for phase conjugating fluorescence. Our method, called
      reference free digital optical phase conjugation, can conjugate extremely weak,
      incoherent optical signals. It was used to phase conjugate fluorescent light
      originating from a bead covered with 0.5 mm of light-scattering tissue. The phase
      conjugated beam refocuses onto the bead and causes a local increase of over two
      orders of magnitude in the light intensity. Potential applications are in
      imaging, optical trapping, and targeted photochemical activation inside turbid
      tissue.

PMID- 22991479
TI  - Electron spin resonance shift and linewidth broadening of nitrogen-vacancy
      centers in diamond as a function of electron irradiation dose.
AB  - A high-nitrogen-concentration diamond sample was subjected to 200-keV electron
      irradiation using a transmission electron microscope. The optical and spin
      resonance properties of the nitrogen-vacancy (NV) color centers were investigated
      as a function of the irradiation dose up to 6.4 * 10(21) e(-)/cm(2). The
      microwave transition frequency of the NV(-) center was found to shift by up to
      0.6% (17.1 MHz) and the linewidth broadened with increasing electron-irradiation
      dose. Unexpectedly, the measured magnetic sensitivity is best at the lowest
      irradiation dose, even though the NV concentration increases monotonically with
      increasing dose. This is in large part due to a sharp reduction in optically
      detected spin contrast at higher doses.

PMID- 22991480
TI  - A method to measure specific absorption rate of nanoparticles in colloidal
      suspension using different configurations of radio-frequency fields.
AB  - We report a method for characterization of the efficiency of radio-frequency (rf)
      heating of nanoparticles (NPs) suspended in an aqueous medium. Measurements were
      carried out for water suspended 5 nm superparamagnetic iron-oxide NPs with 30 nm
      dextran matrix for three different configurations of rf electric and magnetic
      fields. A 30 MHz high-Q resonator was designed to measure samples placed inside a
      parallel plate capacitor and solenoid coil with or without an rf electric field
      shield. All components of rf losses were analyzed and rf electric and magnetic
      field induced heating of NPs and the dispersion medium was determined and
      discussed.

PMID- 22991481
TI  - Laser-induced photo-thermal magnetic imaging.
AB  - Due to the strong scattering nature of biological tissue, optical imaging beyond
      the diffusion limit suffers from low spatial resolution. In this letter, we
      present an imaging technique, laser-induced photo-thermal magnetic imaging (PMI),
      which uses laser illumination to induce temperature increase in a medium and
      magnetic resonance imaging to map the spatially varying temperature, which is
      proportional to absorbed energy. This technique can provide high-resolution
      images of optical absorption and can potentially be used for small animal as well
      as breast cancer and lymph node imaging. First, we describe the theory of PMI,
      including the modeling of light propagation and heat transfer in tissue. We also
      present experimental data with corresponding predictions from theoretical models,
      which show excellent agreement.

PMID- 22991482
TI  - Single-shot quantitative dispersion phase microscopy.
AB  - We present an imaging modality capable of providing high-speed optical dispersion
      measurements of live cells. The technique permits wide-field measurement of the
      optical phase shifts introduced by a sample for multiple discrete wavelengths in
      a single image capture. Utilizing spatial modulation and the wavelength
      dependence of the interference-fringe spacing, average refractive index as a
      function of wavelength is obtained, yielding optical dispersion measurements of
      the sample under observation. Because of its simple and low-cost design, the
      technique can be readily integrated into a standard microscope to collect
      additional diagnostic information about biological cells.

PMID- 22991483
TI  - Computational Study on the Conformations of Gambogic Acid.
AB  - The conformations of gambogic acid were studied using force fields, MM3*, AMBER*,
      MMFFs and OPLS2005, and B3LYP methods. In a model molecule, only the MM3* and
      AMBER* methods produced the same number of conformers as B3LYP, generating two
      conformations for rings 1 and 2, and a single conformation for rings 3 and 4. The
      preferred conformations of these rings are maintained in a conformer of the
      actual gambogic acid generated using the AMBER* and B3LYP methods. Although this
      calculated conformer matches well with the crystal structure, it shows that H43,
      C25=C26 and C30=C31 bonds may be misassigned in the crystal structure.

PMID- 22991484
TI  - Theory of signal and noise in double-gated nanoscale electronic pH sensors.
AB  - The maximum sensitivity of classical nanowire (NW)-based pH sensors is defined by
      the Nernst limit of 59 mV/pH. For typical noise levels in ultra-small single
      gated nanowire sensors, the signal-to-noise ratio is often not sufficient to
      resolve pH changes necessary for a broad range of applications. Recently, a new
      class of double-gated devices was demonstrated to offer apparent "super
      Nernstian" response (>59 mV/pH) by amplifying the original pH signal through
      innovative biasing schemes. However, the pH-sensitivity of these nanoscale
      devices as a function of biasing configurations, number of electrodes, and signal
      to-noise ratio (SNR) remains poorly understood. Even the basic question such as
      "Do double-gated sensors actually resolve smaller changes in pH compared to
      conventional single-gated sensors in the presence of various sources of noise?"
      remains unanswered. In this article, we provide a comprehensive numerical and
      analytical theory of signal and noise of double-gated pH sensors to conclude
      that, while the theoretical lower limit of pH-resolution does not improve for
      double-gated sensors, this new class of sensors does improve the (instrument
      limited) pH resolution.

PMID- 22991485
TI  - Asymmetric bioreduction of activated carbon-carbon double bonds using Shewanella
      yellow enzyme (SYE-4) as novel enoate reductase.
AB  - Shewanella yellow enzyme (SYE-4), a novel recombinant enoate reductase, was
      screened against a variety of different substrates bearing an activated double
      bond, such as unsaturated cyclic ketones, diesters, and substituted imides.
      Dimethyl- and ethyl esters of 2-methylmaleic acid were selectively reduced to (R)
      configured succinic acid derivatives and various N-substituted maleimides
      furnished the desired (R)-products in up to >99% enantiomeric excess. Naturally
      occurring (+)-carvone was selectively reduced to (-)-cis-dihydrocarvone and (-)
      carvone was converted to the diastereomeric product, respectively. Overall SYE-4
      proved to be a useful biocatalyst for the selective reduction of activated C
      000000000000 000000000000 000000000000 111111111111 000000000000 111111111111
      000000000000 000000000000 000000000000 C double bonds and complements the pool of
      synthetic valuable enoate reductases.

PMID- 22991486
TI  - Atherogenic index and high-density lipoprotein cholesterol as cardiovascular risk
      determinants in rheumatoid arthritis: the impact of therapy with biologicals.
AB  - Cardiovascular (CV) diseases are a serious concern in rheumatoid arthritis (RA),
      accounting for approximately one-third to one-half of all RA-related deaths.
      Besides the attempts to identify new risk factors, the proper management of
      traditional CV risk factors such as dyslipidemia should become a priority in the
      periodic evaluation of every RA patient. Atherogenic index has been suggested to
      be less susceptible to disease activity variation during large periods of time,
      making him more attractive to be used in CV risk prediction in this group of
      patients as compared to individual lipids concentrations. Nevertheless,
      inflammation may negatively impact HDL antiatherogenic properties, suggesting
      that HDL function assessment is of particular importance when predicting CV risk
      in these patients. A tight control of inflammation becomes therefore crucial for
      a successful CV risk management. The present paper debates these hypotheses
      focusing on the effects of therapy with biologicals on the above mentioned
      parameters.

PMID- 22991487
TI  - Bringing top-end endoscopy to regional australia: hurdles and benefits.
AB  - This paper focuses on recent experience in setting up an endoscopy unit in a
      large regional hospital. The mix of endoscopy in three smaller hospitals,
      draining into the large hospital endoscopy unit, has enabled the authors to
      comment on practical and achievable steps towards creating best practice
      endoscopy in the regional setting. The challenges of using what is available from
      an infrastructural equipment and personnel setting are discussed. In a fast
      moving field such as endoscopy, new techniques have an important role to play,
      and some are indeed cost effective and have been shown to improve patient care.
      Some of the new techniques and technologies are easily applicable to smaller
      endoscopy units and can be easily integrated into the practice of working
      endoscopists. Cost effectiveness and patient care should always be the final
      arbiter of what is essential, as opposed to what is nice to have. Close
      cooperation between referral and peripheral centers should also guide these
      decisions.

PMID- 22991488
TI  - Prognostic factors and survival in pediatric and adolescent liposarcoma.
AB  - Purpose. Liposarcoma is extremely rare in the pediatric population. To identify
      prognostic factors and determine treatment outcomes, we reviewed our
      institutional experience with pediatric liposarcoma. Methods. We retrospectively
      reviewed all pediatric patients (age <22 years) with confirmed liposarcoma
      treated at Memorial Sloan-Kettering Cancer Center. Histologic subtype, tumor
      location, margin status, recurrence, and adjuvant therapy were analyzed and
      correlated with overall survival. Results. Thirty-four patients (56% male) with a
      median age of 18.1 years were identified. Twenty-two (65%) had peripheral tumors
      and 12 (35%) had centrally located tumors. Histologically, 29 (85%) tumors were
      low grade, and 5 (15%) were high grade pleomorphic. Eleven (32%) had recurrent
      disease, 9 patients with central tumors and 2 patients with peripheral lesions.
      Eight deaths occurred, all in patients with central disease. Five-year overall
      survival was 78%, with a median follow-up time of 5.4 years (range, 0.3-30.3
      years). Tumor grade (P = .003), histologic subtype (P = .01), and primary
      location (P < .001) all correlated with survival, as did stage (P < .001) and
      margin status (P = .001). Conclusions. Central location of the primary tumor,
      high tumor grade, and positive surgical margins are strongly correlated with poor
      survival in pediatric patients with liposarcoma.

PMID- 22991489
TI  - The integration and functional evaluation of rabbit pacing cells transplanted
      into the left ventricular free wall.
AB  - To evaluate the feasibility of cell transplantation to treat bradyarrhythmia, we
      analyzed the in vivo integration and pacing function after transplantation of
      mHCN4-modified rabbit bone marrow mesenchymal stem cells (MSCs) into the rabbit
      left ventricle free wall epicardium. In our investigation, we injected MSCs
      transduced with or without mHCN4 into the rabbit left ventricle free wall
      epicardium. Chemical ablation of the sinoatrial node was performed and bilateral
      vagus nerves were sequentially stimulated to observe premature left ventricular
      contraction or left ventricular rhythm. We found that the mHCN4-transduced MSC
      group had a significantly higher ventricular rate and a shorter QRS duration than
      that of the control and EGFP group. Furthermore, the mHCN4-transduced MSCs, but
      not the control cells, gradually adapted long-spindle morphology and became
      indistinguishable from adjacent ventricle myocytes. The modified MSCs showed
      pacing function approximately 1 week after transplantation and persisted at least
      4 weeks after transplantation. In conclusion, a bradyarrhythmia model can be
      successfully established by chemical ablation of the sinoatrial node and
      sequential bilateral vagus nerve stimulation. The mHCN4-modified rabbit MSCs
      displayed evident dynamic morphology changes after being transplanted into rabbit
      left ventricle free wall epicardium. Our studies may provide a promising strategy
      of using modified stem cell transplantation to treat bradyarrhythmia.

PMID- 22991490
TI  - The 36-item short form health survey: reliability and validity in Chinese medical
      students.
AB  - OBJECTIVE: The 36-Item Short Form Health Survey (SF-36) is widely validated and
      popularly used in assessing the subjective quality of life (QOL) of patients and
      the general public. The aim of the study is to assess the psychometric properties
      of the 36-Item Short Form Health Survey (SF-36) in medical students in mainland
      of China. METHODS: The reliability and validity of the 36-Item Short Form Health
      Survey (SF-36) questionnaire were assessed by conducting a cross-sectional study
      of Chinese medical students in December 2011. All 1358 3(rd) year and 4(th) year
      medical students from 46 classes at China Medical University were investigated.
      RESULTS: The overall Cronbach's alpha coefficient of the SF-36 questionnaire was
      0.791, while the respective Cronbach's alpha coefficients for each of the seven
      dimensions were > 0.70, except where the social function dimension was 0.631.
      Results showed that the SF-36 questionnaire was reliable and valid. CONCLUSION:
      In general, this study provides evidence that the SF-36 questionnaire is suitable
      measures for assess the QOL of medical students in China.

PMID- 22991491
TI  - A review of the human clinical studies involving Citrus aurantium (bitter orange)
      extract and its primary protoalkaloid p-synephrine.
AB  - This review summarizes the published as well as unpublished human studies
      involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid
      p-synephrine, providing information and an assessment of the safety and efficacy
      of these widely used products. The results of over 20 studies involving a total
      of approximately 360 subjects that consumed p-synephrine alone or in combination
      with other ingredients are reviewed and critiqued. Over 50 % of the subjects
      involved in these studies were overweight/obese, and approximately two-thirds of
      these overweight/obese subjects consumed caffeine (132-528 mg/day) in conjunction
      with p-synephrine (10-53 mg/day). Bitter orange/p-synephrine containing products
      were consumed for up to 12 weeks. Approximately 44 % of the subjects consumed a
      bitter orange/p-synephrine only product, while the remainder consumed a complex
      product that contained multiple ingredients in addition to p-synephrine. In
      general, bitter orange extract alone (p-synephrine) or in combination with other
      herbal ingredients did not produce significant adverse events as an increase in
      heart rate or blood pressure, or alter electrocardiographic data, serum
      chemistry, blood cell counts or urinalysis. p-Synephrine alone as well as in
      combination products were shown to increase resting metabolic rate and energy
      expenditure, and modest increases in weight loss were observed with bitter orange
      extract/p-synephrine-containing products when given for six to 12 weeks. Longer
      term studies are needed to further assess the efficacy of these products and
      affirm their safety under these conditions.

PMID- 22991492
TI  - Gender difference in prevalence of signs and symptoms of temporomandibular joint
      disorders: a retrospective study on 243 consecutive patients.
AB  - BACKGROUND: This study evaluated the prevalence of the signs and symptoms of
      temporomandibular joint disorder (TMD) among patients with TMD symptoms. METHODS:
      Between September 2011 and December 2011, 243 consecutive patients (171 females,
      72 males, mean age 41 years) who were referred to the Department of
      Prosthodontics, Faculty of Dentistry, Karadeniz Technical University, Trabzon
      were examined physically and completed a questionnaire regarding age, gender,
      social status, general health, antidepressant drug usage, dental status, limited
      mouth opening, temporomandibular joint (TMJ) sounds, and parafunctions (bruxism,
      clenching). The data were analyzed using the chi-square test and binary logistic
      regression model (alpha = 0.05). RESULTS: With a frequency of 92%, pain in the
      temporal muscle was the most common symptom, followed by pain during mouth
      opening (89%) in both genders. TMJ pain at rest, pain in the masseter muscle,
      clicking, grinding, and anti-depressant use were significantly more frequent in
      females than males. Age (p=0.006; odds ratio 0.954; 95% CI 0.922-0.987) and
      missing teeth (p=0.003; odds ratio 3.753; 95% CI 1.589-8.863) had significant
      effects on the prevalence of TMD. CONCLUSION: Females had TMD signs and symptoms
      more frequently than males in the study population. The most common problem in
      both genders was pain.

PMID- 22991493
TI  - Role of mitochondrial translocation of telomerase in hepatocellular carcinoma
      cells with multidrug resistance.
AB  - Multidrug resistance (MDR) is a major obstacle of cancer chemotherapy. This study
      aimed to investigate the role of mitochondrial translocation of telomerase
      (hTERT) in MDR of human hepatocellular carcinoma (HCC) cells. In this study,
      three HCC cell lines (SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3
      cells) with differential resistance index (RI) to cisplatin (CDDP) were induced
      by pulse treatment of SK-Hep1 (human hepatocellular cell line) with CDDP in
      vitro. The RI of SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells
      was 5.14, 8.66, and 14.25, respectively, and all the cell lines showed cross
      resistance to Doxorubicin (DOX) and 5-Fuorouracil (5-FU). The apoptosis rates in
      drug-resistant cells were significantly reduced. Cell cycle analysis revealed the
      ratio of drug-resistant cells in G2/M and S phases increased, while that in G1
      phase decreased. Immunofluorescence staining and Western blot assay demonstrated,
      with the gradual elevation in RI, increasing hTERT translocated from the nuclei
      to the mitochondria, while real-time PCR indicated the shortening of telomere
      length in drug-resistant cells under the chemotherapeutic stress and the
      reduction of damaged mtDNA with the increase in RI. Furthermore, JC-1 staining
      also indicated the reduction of mitochondrial membrane potential in drug
      resistant cells. The mitochondrial translocation of hTERT increases in multidrug
      resistant cells and exerts protective effect on mitochondrial function. Drug
      resistant tumor cells escape from apoptosis through hTERT-mediated mitochondrial
      protection. Mitochondrial translocation of hTERT may serve as an underlying
      mechanism of MDR.

PMID- 22991494
TI  - Cytotoxicity of 15-deoxy-Delta(12,14)-prostaglandin J(2) through PPARgamma
      independent pathway and the involvement of the JNK and Akt pathway in renal cell
      carcinoma.
AB  - INTRODUCTION: Agonists of peroxisome proliferator-activated receptor gamma
      (PPARgamma) have been examined as chemopreventive and chemotherapeutic agents.
      The aim was to investigate the cytotoxicity and action mechanisms of 15-deoxy
      Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), one of endogenous ligands for
      PPARgamma, in terms of PPARgamma-dependency and the mitogen-activated protein
      kinase (MAPK) and Akt pathway in three human renal cell carcinoma (RCC)-derived
      cell lines. METHODS: 786-O, Caki-2 and ACHN cells were used as human RCC-derived
      cell lines. Cell viability and caspase-3 activity was detected by fluorescent
      reagents, and chromatin-condensation was observed with a brightfield fluorescent
      microscope after staining cells with Hoechst33342. The expression levels of
      proteins were detected by Western blot analysis. RESULTS: 15d-PGJ(2) showed
      cytotoxicity in dose-dependent manner. 15d-PGJ(2) induced chromatin-condensation
      and elevated caspase-3 activity, and the cell viability was restored by co
      treatment with a pan-caspase inhibitor, Z-VAD-FMK, indicating the involvement of
      caspase-dependent apoptosis. The cytotoxicity was not impaired by a PPARgamma
      inhibitor, GW9662, suggesting that 15d-PGJ(2) exerted the cytotoxicity in a
      PPARgamma-independent manner. Some antioxidants rescued cells from cell death
      induced by 15d-PGJ(2), but some did not, suggesting that reactive oxygen species
      (ROS) did not contribute to the apoptosis. 15d-PGJ(2) also increased the
      expression levels of phospho-c-Jun N terminal kinase (JNK) in Caki-2 cells, and
      decreased those of phospho-Akt in 786-O cells, indicating that the JNK MAPK and
      the Akt pathways participated in the anticancer effects of 15d-PGJ(2) in some
      cell lines. CONCLUSION: 15d-PGJ(2) exerted cytotoxic effects accompanying caspase
      dependent apoptosis, and this effect was elicited in a PPARgamma-independent
      manner in three cell lines. In addition, the JNK MAPK and Akt pathway was
      involved in the cytotoxicity of 15d-PGJ(2) to some extent in some cell line.
      Therefore, our study showed the 15d-PGJ(2) to potentially be an interesting
      approach for RCC treatment.

PMID- 22991495
TI  - Preoperative management of surgical patients by "shortened fasting time": a study
      on the amount of total body water by multi-frequency impedance method.
AB  - AIM: Preoperative fasting is an established procedure to be practiced for
      patients before surgery, but optimal preoperative fasting time still remains
      controversial. The aim of this study was to investigate the effect of "shortened
      preoperative fasting time" on the change in the amount of total body water (TBW)
      in elective surgical patients. TBW was measured by multi-frequency impedance
      method. METHODS: The patients, who were scheduled to undergo surgery for stomach
      cancer, were divided into two groups of 15 patients each. Before surgery,
      patients in the control group were managed with conventional preoperative fasting
      time, while patients in the "enhanced recovery after surgery (ERAS)" group were
      managed with "shortened preoperative fasting time" and "reduced laxative
      medication." TBW was measured on the day before surgery and the day of surgery
      before entering the operating room. Defecation times and anesthesia-related
      vomiting and aspiration were monitored. RESULTS: TBW values on the day of surgery
      showed changes in both groups as compared with those on the day before surgery,
      but the rate of change was smaller in the ERAS group than in the control group
      (2.4+/-6.8% [12 patients] vs. -10.6+/-4.6% [14 patients], p<0.001). Defecation
      times were less in the ERAS group. Vomiting and aspiration were not observed in
      either group. CONCLUSION: The results suggest that preoperative management with
      "shorted preoperative fasting time" and "reduced administration of laxatives" is
      effective in the maintenance of TBW in elective surgical patients.

PMID- 22991496
TI  - Impaired secretion of total glucagon-like peptide-1 in people with impaired
      fasting glucose combined impaired glucose tolerance.
AB  - OBJECTIVE: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for
      Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus
      (NDDM) during oral glucose tolerance test (OGTT). The relationships between total
      GLP-1 level and islet beta cell function, insulin resistance (IR) and insulin
      sensitivity (IS) were also investigated. METHODS: A 75g glucose OGTT was given to
      531 subjects. Based on the results, they were divided into groups of normal
      glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated
      impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP
      1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment
      of beta cell function (HOMA-beta), HOMA of insulin resistance (HOMA-IR), Gutt and
      Matsuda indexes were calculated. The relationships between GLP-1 level and beta
      cell function, IR and IS were analyzed. RESULTS: The levels of total fasting GLP
      1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (?GLP-1) following OGTT
      reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-beta , HOMA-IR,
      Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG,
      isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation
      analysis and multivariable linear regression model suggested that some levels of
      correlation between GLP-1 levels, ?GLP-1 and beta cell function, IR (P<0.05).
      CONCLUSIONS: The total GLP-1 levels and its response to glucose load decreased
      significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were
      even similar to that of NDDM group. Moreover, there were observable correlations
      between impaired GLP-1 secretion and beta cell function, IR and IS.

PMID- 22991497
TI  - Molecular and biochemical characterization of a novel beta-N-acetyl-D
      hexosaminidase with broad substrate-spectrum from the Aisan corn borer, Ostrinia
      furnacalis.
AB  - Insect beta-N-acetyl-D-hexosaminidases with broad substrate-spectrum (IBS-Hex)
      are the homologues of human beta-N-acetyl-D-hexosaminidase A/B (HsHex A/ B).
      These enzymes are distributed in most insect species and vary in physiological
      roles. In this study, the gene encoding an IBS-Hex, OfHEX2, was cloned from the
      Asian corn borer, Ostrinia furnacalis. Recombinant OfHex2 was expressed in Pichia
      pastoris and purified to homogeneity. By structure-based sequence alignment,
      three sequence segments with high diversity among IBS-Hexs were firstly
      concluded. Furthermore, the residue pair N423-R424/ D452-L453 important for the
      specificity of human beta-N-acetyl-D-hexosaminidase subunits alpha/beta toward
      charged/ non-charged substrates was not conserved in OfHex2 and other IBS-Hexs.
      Unlike HsHex A, OfHex2 could not degrade charged substrates such as 4
      methylumbelliferyl-6-sulfo-N-acetyl-beta-D-glucosaminide, ganglioside GM2 and
      peptidoglycan. OfHex2 showed a broad substrate-spectrum by hydrolyzing beta1-2
      linked N-acetyl-D-glucosamines from both alpha3 and alpha6 branches of
      biantennary N-glycan and beta1-4 linked GlcNAc from chitooligosaccharides as well
      as beta1-3 linked or beta1-4 linked N-acetyl-D-galactosamine from
      oligosaccharides of glycolipids. Real-time PCR analysis demonstrated that the
      expression of OfHEX2 was up-regulated in the intermolt stages (both larva and
      pupa), and mainly occurred in the carcass rather than in the midgut during the
      feeding stage of fifth (final) instar larva. This study reported a novel IBS-Hex
      with specific biochemical properties, suggesting biodiversity of this class of
      enzymes.

PMID- 22991498
TI  - Molecular characterization of an ice nucleation protein variant (inaQ) from
      Pseudomonas syringae and the analysis of its transmembrane transport activity in
      Escherichia coli.
AB  - The ice nucleation protein (INP) of Pseudomonas syringae has gained scientific
      interest not only because of its pathogenicity of foliar necroses but also for
      its wide range of potential applications, such as in snow making, frozen food
      preparation, and surface-display system development. However, studies on the
      transport activity of INP remain lacking. In the present study, a newly
      identified INP-gene variant, inaQ, from a P. syringae MB03 strain was cloned. Its
      structural domains, signal sequences, and the hydrophilicity or hydrophobicity of
      each domain, were then characterized. The deduced amino acid sequence of InaQ
      shares similar protein domains with three P. syringae INPs, namely, InaK, InaZ,
      and InaV, which were identified as an N-terminal domain, a central repeating
      domain, and a C-terminal domain. The expression of the full-length InaQ and of
      various truncated variants was induced in Escherichia coli to analyze their
      transmembrane transport and surface-binding activities, while using the green
      fluorescence protein (GFP) as the fusion partner. With two transmembrane segments
      and a weak secretion signal, the N-terminal domain (InaQ-N) alone was found to be
      responsible for the transport process as well as for the binding to the outer
      membrane, whereas the C-terminal region was nonfunctional in protein transport.
      Increased membrane transport and surface-binding capacities were induced by a low
      isopropyl-beta-D-thiogalactoside concentration (0.1 mmol/l) but not by culture
      temperatures (15 oC to 37 oC). Furthermore, by constructing the GFP-fused
      proteins with a single InaQ-N, as well as two and three tandemly aligned InaQ-N
      molecules, the transport and membrane-binding activities of these proteins were
      compared using Western blot analysis, immmunofluorescence microscopy, and assays
      of the GFP specific fluorescence intensity of subcellular fractions and flow
      cytometry, which showed that the increase of InaQ-N repeats resulted in a
      coordinated increase of the surface-immobilization efficiency. Therefore, the
      results of this study can serve as a molecular basis for improving the
      performance of INP-based cell surface-display systems.

PMID- 22991500
TI  - Why would plant species become extinct locally if growing conditions improve?
AB  - Two assumptions underlie current models of the geographical ranges of perennial
      plant species: 1. current ranges are in equilibrium with the prevailing climate,
      and 2. changes are attributable to changes in macroclimatic factors, including
      tolerance of winter cold, the duration of the growing season, and water stress
      during the growing season, rather than to biotic interactions. These assumptions
      allow model parameters to be estimated from current species ranges. Deterioration
      of growing conditions due to climate change, e.g. more severe drought, will cause
      local extinction. However, for many plant species, the predicted climate change
      of higher minimum temperatures and longer growing seasons means, improved growing
      conditions. Biogeographical models may under some circumstances predict that a
      species will become locally extinct, despite improved growing conditions, because
      they are based on an assumption of equilibrium and this forces the species range
      to match the species-specific macroclimatic thresholds. We argue that such model
      predictions should be rejected unless there is evidence either that competition
      influences the position of the range margins or that a certain physiological
      mechanism associated with the apparent improvement in growing conditions
      negatively affects the species performance. We illustrate how a process-based
      vegetation model can be used to ascertain whether such a physiological cause
      exists. To avoid potential modelling errors of this type, we propose a method
      that constrains the scenario predictions of the envelope models by changing the
      geographical distribution of the dominant plant functional type. Consistent
      modelling results are very important for evaluating how changes in species areas
      affect local functional trait diversity and hence ecosystem functioning and
      resilience, and for inferring the implications for conservation management in the
      face of climate change.

PMID- 22991499
TI  - Interferon-gamma-induced nitric oxide inhibits the proliferation of murine renal
      cell carcinoma cells.
AB  - Renal cell carcinoma (RCC) remains one of the most resistant tumors to systemic
      chemotherapy, radiotherapy, and immunotherapy. Despite great progress in
      understanding the basic biology of RCC, the rate of responses in animal models
      and clinical trials using interferons (IFNs) has not improved significantly. It
      is likely that the lack of responses can be due to the tumor's ability to develop
      tumor escape strategies. Currently, the use of targeted therapies has improved
      the clinical outcomes of patients with RCC and is associated with an increase of
      Th1-cytokine responses (IFNgamma), indicating the importance of IFNgamma in
      inhibiting tumor proliferation. Thus, the present study was designed to
      investigate a new mechanism by which IFNgamma mediates direct anti-proliferative
      effects against murine renal cell carcinoma cell lines. When cultured RCC cell
      lines were exposed to murine recombinant IFNgamma, a dose dependent growth
      inhibition in CL-2 and CL-19 cells was observed; this effect was not observed in
      Renca cells. Growth inhibition in CL-2 and CL-19 cell lines was associated with
      the intracellular induction of nitric oxide synthase (iNOS) protein, resulting in
      a sustained elevation of nitric oxide (NO) and citrulline, and a decrease in
      arginase activity. The inhibition of cell proliferation appears to be due to an
      arrest in the cell cycle. The results indicate that in certain RCC cell lines,
      IFNgamma modulates L-arginine metabolism by shifting from arginase to iNOS
      activity, thereby developing a potent inhibitory mechanism to encumber tumor cell
      proliferation and survival. Elucidating the cellular events triggered by IFNgamma
      in murine RCC cell lines will permit anti-tumor effects to be exploited in the
      development of new combination therapies that interfere with L-arginine
      metabolism to effectively combat RCC in patients.

PMID- 22991501
TI  - FOXC1 contributes to microvascular invasion in primary hepatocellular carcinoma
      via regulating epithelial-mesenchymal transition.
AB  - The existence of microvascular invasion (MVI) formation is one of the most
      important risk factors predicting poor outcome in hepatocellular carcinoma (HCC)
      and its mechanism remains largely unknown. Epithelial-Mesenchymal Transition
      (EMT) has been suggested to be involved in many steps of the invasion-metastasis
      cascade. To elucidate the possible contribution of EMT to MVI, we initially
      evaluated the expression of 8 EMT-related transcription factors (TFs) in HCC
      patients with or without MVI and found that FOXC1 expression was significantly
      higher in patients with MVI than those without MVI (P < 0.05). Knockdown of FOXC1
      expression in HCC cells resulted in a partial conversion of their EMT progresses,
      mainly regulating the mesenchymal component. Ectopic expression of snail, twist
      or TGF-beta1 could induce expression of FOXC1, but none of the expression of
      snail, twist, slug or TGF-beta was consistently down-regulated in response to
      FOXC1 silencing, suggesting FOXC1 might operate the downstream of other EMT
      regulators. In addition, knockdown of FOXC1 expression led to cytoskeleton
      modification accompanied by decreased ability of cell proliferation, migration,
      and invasion. Meanwhile, some matrix metalloproteinases (MMPs) and VEGF-A were
      also simultaneously down-regulated. Together, our findings demonstrate that FOXC1
      is one of candidate predictive markers of MVI, and that inhibition of FOXC1
      expression can partially reverse EMT program, offering a potential molecular
      therapeutic target for reducing tumor metastasis in HCC patients.

PMID- 22991502
TI  - Comparative Genome Sequence Analysis Reveals the Extent of Diversity and
      Conservation for Glycan-Associated Proteins in Burkholderia spp.
AB  - Members of the Burkholderia family occupy diverse ecological niches. In
      pathogenic family members, glycan-associated proteins are often linked to
      functions that include virulence, protein conformation maintenance, surface
      recognition, cell adhesion, and immune system evasion. Comparative analysis of
      available Burkholderia genomes has revealed a core set of 178 glycan-associated
      proteins shared by all Burkholderia of which 68 are homologous to known essential
      genes. The genome sequence comparisons revealed insights into species-specific
      gene acquisitions through gene transfers, identified an S-layer protein, and
      proposed that significantly reactive surface proteins are associated to sugar
      moieties as a potential means to circumvent host defense mechanisms. The
      comparative analysis using a curated database of search queries enabled us to
      gain insights into the extent of conservation and diversity, as well as the
      possible virulence-associated roles of glycan-associated proteins in members of
      the Burkholderia spp. The curated list of glycan-associated proteins used can
      also be directed to screen other genomes for glycan-associated homologs.

PMID- 22991503
TI  - A systems approach and skeletal myogenesis.
AB  - Skeletal myogenesis depends on the strict regulation of the expression of various
      gene subsets. Therefore, the understanding of genome wide gene regulation is
      imperative for elucidation of skeletal myogenesis. In recent years, systems
      approach has contributed to the understanding of various biological processes.
      Our group recently revealed the critical genome network of skeletal myogenesis by
      using a novel systems approach combined with whole-mount in situ hybridization
      (WISH) database, high-throughput screening, and microarray analysis. In this
      paper, we introduce our systems approach for understanding the myogenesis
      regulatory network and describe the advantages of systems approach.

PMID- 22991504
TI  - Coordinated Regulation of PPARgamma Expression and Activity through Control of
      Chromatin Structure in Adipogenesis and Obesity.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is required for differentiation and function of mature adipocytes. Its expression
      is induced during adipogenesis where it plays a key role in establishing the
      transcriptome of terminally differentiated white fat cells. Here, we review
      findings indicating that PPARgamma expression and activity are intricately
      regulated through control of chromatin structure. Hierarchical and combinatorial
      activation of transcription factors, noncoding RNAs, and chromatin remodelers
      allows for temporally controlled expression of PPARgamma and its target genes
      through sequential chromatin remodelling. In obesity, these regulatory pathways
      may be altered and lead to modified PPARgamma activity.

PMID- 22991507
TI  - Composite match index with application of interior deformation field measurement
      from magnetic resonance volumetric images of human tissues.
AB  - Whereas a variety of different feature-point matching approaches have been
      reported in computer vision, few feature-point matching approaches employed in
      images from nonrigid, nonuniform human tissues have been reported. The present
      work is concerned with interior deformation field measurement of complex human
      tissues from three-dimensional magnetic resonance (MR) volumetric images. To
      improve the reliability of matching results, this paper proposes composite match
      index (CMI) as the foundation of multimethod fusion methods to increase the
      reliability of these various methods. Thereinto, we discuss the definition,
      components, and weight determination of CMI. To test the validity of the proposed
      approach, it is applied to actual MR volumetric images obtained from a
      volunteer's calf. The main result is consistent with the actual condition.

PMID- 22991505
TI  - The role of peroxisome proliferator-activated receptors in the esophageal,
      gastric, and colorectal cancer.
AB  - Tumors of the gastrointestinal tract are among the most frequent human
      malignancies and account for approximately 30% of cancer-related deaths
      worldwide. Peroxisome proliferator-activated receptors (PPARs) are ligand
      activated transcription factors that control diverse cellular functions such as
      proliferation, differentiation, and cell death. Owing to their involvement in so
      many processes, they play crucial roles also in the development and physiology of
      the gastrointestinal tract. Consistently, PPARs deregulation has been implicated
      in several pathophysiological conditions, including chronic inflammation and
      cancer development. This paper summarizes the current knowledge on the role that
      the various PPAR isoforms play in the pathogenesis of the esophageal, gastric,
      and intestinal cancer. Elucidation of the molecular mechanisms underlying PPARs'
      signaling pathways will provide insights into their possible use as predictive
      biomarkers in the initial stages of the process. In addition, this understanding
      will provide the basis for new molecular targets in cancer therapy and
      chemoprevention.

PMID- 22991506
TI  - Dysregulation of Dicer1 in beta cells impairs islet architecture and glucose
      metabolism.
AB  - microRNAs (miRNAs) play important roles in pancreas development and in regulation
      of insulin expression in the adult. Here we show that loss of miRNAs activity in
      beta-cells during embryonic development results in lower beta-cell mass and in
      impaired glucose tolerance. Dicer1-null cells initially constitute a significant
      portion of the total beta-cell population. However, during postnatal development,
      Dicer1-null cells are depleted. Furthermore, wild-type beta cells are
      repopulating the islets in complex compensatory dynamics. Because loss of Dicer1
      is also associated with changes in the distribution of membranous E-cadherin, we
      hypothesized that E-cadherin activity may play a role in beta cell survival or
      islet architecture. However, genetic loss of E-cadherin function does not impair
      islet architecture, suggesting that miRNAs likely function through other or
      redundant effectors in the endocrine pancreas.

PMID- 22991508
TI  - Risk factors for recurrence of symptomatic common bile duct stones after
      cholecystectomy.
AB  - Purpose. The recurrence of CBD stone is still observed in a considerable number
      of patients. The study was to evaluate the risk factors for recurrence of
      symptomatic CBD stone in patients who underwent cholecystectomy after the removal
      of CBD stone. Methods. The medical records of patients who underwent removal of
      CBD stone with subsequent cholecystectomy were reviewed. The risk factors for the
      recurrence of symptomatic CBD stone were compared between the recurrence and the
      nonrecurrence group. Results. The mean follow-up period was 40.6 months. The
      recurrence of symptomatic CBD stones was defined as the detection of bile duct
      stones no sooner than 6 months after complete clearance of CBD stones, based on
      symptoms or signs of biliary complication. 144 patients (68 males, 47.2%) were
      finally enrolled and their mean age was 59.8 (range: 26~86) years. The recurrence
      of CBD stone occurred in 15 patients (10.4%). The mean period until first
      recurrence was 25.9 months. The presence of type 1 or 2 periampullary
      diverticulum and multiple CBD stones were the independent risk factors.
      Conclusion. For the patients with type 1 or 2 periampullary diverticulum or
      multiple CBD stones, careful followup is needed for the risk in recurrence of
      symptomatic CBD stone.

PMID- 22991509
TI  - How many diseases are colorectal cancer?
AB  - The development of personalised therapy and mechanism-targeted agents in oncology
      mandates the identification of the patient populations most likely to benefit
      from therapy. This paper discusses the increasing evidence as to the
      heterogeneity of the group of diseases called colorectal cancer. Differences in
      the aetiology and epidemiology of proximal and distal cancers are reflected in
      different clinical behaviour, histopathology, and molecular characteristics of
      these tumours. This may impact response both to standard cytotoxic therapies and
      mechanism-targeted agents. This disease heterogeneity leads to challenges in the
      design of clinical trials to assess novel therapies in the treatment of
      "colorectal cancer."

PMID- 22991511
TI  - The Validity of the WHO-5 as an Early Screening for Apathy in an Elderly
      Population.
AB  - Aim. The objective of our study has been to evaluate the WHO-5 as a new early
      screening instrument for apathy in a group of elderly persons. Methods. The WHO-5
      was compared to the Geriatric Depression Scale (GDS-15). The GDS contains five
      items measuring well-being and ten items measuring depression. The internal
      validity of the WHO-5 (total score being a sufficient statistic) was evaluated
      with both parametric and nonparametric item response theory models. The external
      validity of the WHO-5 and the GDS was evaluated by ROC using depression as index
      of validity. Results. The item response theory analyses confirmed that the total
      score of the WHO-5 is a sufficient statistic. The ROC analysis shows an adequate
      sensitivity (61%) and specificity (84%). The GDS(15) and its two subscales
      obtained low sensitivity (25-42%), but high specificity (90-98%). Conclusion. The
      WHO-5 was found both internally and externally valid when considering decreased
      positive well-being to be an early indication of apathy reflecting that the wind
      has begun to be taken out of the "motivation sail."

PMID- 22991510
TI  - Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the
      Bladder: A Systematic Review and Meta-Analysis.
AB  - The prognostic importance of examining ErbB receptor family expression in human
      bladder cancer remains uncertain. Using published evidence, we examined the
      clinical value and the updated results of clinical trials targeting ErbB receptor
      family members. Twenty-seven articles from 65 references related to ErbB receptor
      expression assessment in bladder cancer were reviewed. The estimates included the
      association significance, hazard ratios, and 95% confidence intervals (CIs) from
      actuarial curves and survival analyses. A meta-analysis was done on those reports
      using univariate log-rank tests or a Cox-regression model. The methods of
      analysis and study subjects chosen varied widely among studies. The overall risks
      of disease progression for patients with EGFR or ErbB2 overexpression were 4.5
      (95% CI: 2.5-8.4) and 1.1 (95% CI: 0.6-1.9), and the risks of mortality were 3.0
      (95% CI: 1.6-5.9) and 1.1 (95% CI: 1.0-1.2), respectively. However, the
      significance of coexpression patterns of the ErbB receptor family remains
      controversial. None of six clinical trials yielded convincing results for
      blockading ErbB receptor signaling in urothelial carcinoma. The results of this
      analysis suggest that assessing co-expression patterns of the ErbB family may
      provide better prognostic information for bladder cancer patients.

PMID- 22991512
TI  - Ion channel-target toxicology.

PMID- 22991513
TI  - Influence of light-curing mode on the erosion preventive effect of three
      different resin-based surface sealants.
AB  - Objectives. To investigate if reducing the light-curing time (while maintaining
      similar energy density) of resin-based surface sealants influences their erosion
      preventive potential and mechanical stability after thermomechanical loading.
      Methods. Dentine samples were treated as follows: group 1-untreated, groups 2-4
      Seal&Protect, groups 5-7-experimental sealer, and groups 8-10-Syntac Classic
      system. Groups 2, 5 and 8 were light-cured for 10 s (1000 mW/cm(2)), groups 3, 6
      and 9 for 7 s (1400 mW/cm(2)), and groups 4, 7, and 10 for 3 s (3200 mW/cm(2)).
      After water storage (7 d), first measurement was performed to evaluate baseline
      permeability of the sealants. After a thermomechanical loading (5000 cycles, 50/5
      degrees C, 12000 brushing strokes) a second evaluation of permeability was
      conducted (measurement 2). Permeability was tested by storing the samples in HCl
      (pH 2.3; 24 h) and measuring the dentine calcium release by atomic absorption
      spectroscopy. Results. For the first and second measurements, no influence of
      light-exposure time on permeability was observed (ANOVA: P > 0.05). No
      significant difference in the stability of the respective sealants was observed
      when light-cured for different durations. Conclusion. Shortening the light-curing
      time, while maintaining energy density constant, has no influence on permeability
      and stability of the investigated sealants.

PMID- 22991515
TI  - Laryngopharyngeal reflux.

PMID- 22991516
TI  - Transcriptional Read-Through Induction Treatment Trial in Intestinal Failure
      Induced by an EpCAM Nonsense Mutation.
AB  - Congenital tufting enteropathy (CTE) is a rare autosomal recessive diarrheal
      disorder where epithelial tufts can be present from the duodenum to the large
      intestine. CTE has been linked to mutations in the epithelial cell adhesion
      molecule gene (EpCAM) Sivagnanam et al. (2008). We recently reported the first
      case with a nonsense mutation in EpCAM Sivagnanam et al. (2010). Here, we
      explored the clinical and molecular effects of enterally administered gentamicin
      in this CTE patient. Altogether, our findings indicate that the therapy employed
      was insufficient to produce notable read-through induction of the EpCAM premature
      termination codon. This report highlights the utility of genetic testing not only
      in respect of diagnostics, prognostics, and family planning, but potential
      mutation-specific therapeutic considerations as well.

PMID- 22991514
TI  - Electromagnetic fields, oxidative stress, and neurodegeneration.
AB  - Electromagnetic fields (EMFs) originating both from both natural and manmade
      sources permeate our environment. As people are continuously exposed to EMFs in
      everyday life, it is a matter of great debate whether they can be harmful to
      human health. On the basis of two decades of epidemiological studies, an
      increased risk for childhood leukemia associated with Extremely Low Frequency
      fields has been consistently assessed, inducing the International Agency for
      Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs
      interaction with biological systems may cause oxidative stress under certain
      circumstances. Since free radicals are essential for brain physiological
      processes and pathological degeneration, research focusing on the possible
      influence of the EMFs-driven oxidative stress is still in progress, especially in
      the light of recent studies suggesting that EMFs may contribute to the etiology
      of neurodegenerative disorders. This review synthesizes the emerging evidences
      about this topic, highlighting the wide data uncertainty that still characterizes
      the EMFs effect on oxidative stress modulation, as both pro-oxidant and
      neuroprotective effects have been documented. Care should be taken to avoid
      methodological limitations and to determine the patho-physiological relevance of
      any alteration found in EMFs-exposed biological system.

PMID- 22991517
TI  - An unusual presentation of herpes simplex virus encephalitis.
AB  - We present a case of a 65-year-old man with an acute alteration in mental state
      that was initially diagnosed as a functional psychiatric condition. After
      extensive workup, herpes simplex virus type 1 (HSV-1) was detected in the
      patient's cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and he
      responded rapidly to treatment with acyclovir. The case illustrates the
      importance of actively excluding organic causes in such patients, the need to
      have a low threshold of suspicion for HSV encephalitis, and the central role of
      CSF PCR testing for the diagnosis of HSV encephalitis, even in the absence of CSF
      biochemical abnormalities.

PMID- 22991518
TI  - Favorable Outcome of Ramsay Hunt Syndrome under Dexamethasone.
AB  - A 20-year-old student under chronic stress developed a painful reddish left ear,
      vesicles on the left ear, severe left-sided peripheral facial-nerve palsy, and
      hypoesthesia of the left upper lip, after exposure to a ventilator. Ramsay Hunt
      syndrome was diagnosed. Instead of prednisolone she received dexamethasone (40
      mg/d) but nonetheless recovered completely after 12 weeks.

PMID- 22991519
TI  - Lithium-associated thyromegaly: an unusual cause of airway obstruction.
AB  - Acute upper airway obstruction is a medical emergency and can be caused by many
      serious conditions such as a foreign body occluding the airway, intrinsic
      swelling (as in anaphylaxis), or extrinsic compression. Thyromegaly has rarely
      been reported as a source of airway compromise. We present a patient whose
      thyromegaly is presumed to have been induced by lithium and was massive enough to
      cause severe airway compromise.

PMID- 22991520
TI  - CT Diagnosis of a Thoracic Aort Aneurysm with Type B Aortic Dissection Clinically
      Misdiagnosed as Acute Pulmonary Embolism.
AB  - A 54-year-old man was admitted to the emergency department, presenting with an
      acute onset of chest pain and severe respiratory distress symptoms. He was
      medicated with intravenous analgesia and antihypertensive drugs. The patient was
      subjected to a chest X-ray which revealed a prominent widening of the mediastinum
      and pleural effusion on the left side. In laboratory tests-d-dimer level was
      highly elevated. The patient was clinically interpreted as having an acute
      pulmonary embolism and referred to the radiology clinic to perform a computed
      tomography (CT) examination. Contrast-enhanced CT demonstrated that there was no
      abnormality related to the pulmonary vasculature, but a huge thoracic aorta
      aneurysm measuring 11 * 8.1 * 7.7 cm in diameter was detected. Accompanying the
      aneurysm, an intimal flap was also present in the proximal descending thoracic
      aorta, distal to the origin of the left subclavian artery and extending into the
      bifurcation level. The patient was therefore diagnosed as having a type B aortic
      dissection as well. Once these serious conditions were detected, he was
      immediately transferred to a cardiovascular thoracic surgery hospital for
      endovascular repairment operation.

PMID- 22991522
TI  - Noncaged laying hens remain unflappable while wearing body-mounted sensors:
      Levels of agonistic behaviors remain unchanged and resource use is not reduced
      after habituation.
AB  - Unique markings or body-mounted sensors facilitate data collection from
      individuals in large groups of similar-looking conspecifics but may have
      unintended consequences on behavior. A wireless sensor attached to the back of
      laying hens via a harness has been developed to monitor space use and activity.
      Prior to collecting experimental data, effects of the sensor on resource use and
      social interactions were assessed. Four rooms of 135 hens each were weighed and
      10 hens/room were randomly fitted with sensors at 11 wk of age (0 d).
      Instantaneous scan samples recorded the number of hens (SEN: sensor-wearing hen,
      and NON: hen without sensor) using resources (feeder, water, nest box, perch)
      every 5 min over 24 h on -5 d, -4 d, -2 d, -1 d, 1 d, 2 d, 4 d, 8 d, and 16 d.
      Logistic regression determined that SEN feeder use was less on 1 d and 2 d and
      more on 16 d than NON feeder use. The SEN water use was reduced only on 1 d. The
      SEN nest box use increased on 1 d, 2 d, and 16 d. The SEN perched more on 1 d, 2
      d, and 4 d, and less on 8 d. Initial resource use was affected by wearing a
      sensor, but by 16 d, all resources were used similarly or more by SEN than NON.
      No difference in BW was observed on 17 d, suggesting that long-term resource use
      was not affected. No differences were observed among the number of agonistic
      observations -5 d, 8 d, and 16 d. With the exception of SEN hens acting as
      aggressors toward NON hens, agonistic interaction types occurred close to
      expected proportions. These factors indicate that hens habituate to wearing
      sensors within 2 wk.

PMID- 22991521
TI  - Public Knowledge about and Detection of Canine Visceral Leishmaniasis in Urban
      Divinopolis, Brazil.
AB  - Background. Leishmaniases are diseases with a wide spectrum of clinical
      manifestations including cutaneous (CL) and visceral (VL) forms. Many factors may
      affect their occurrence and expansion including environmental, geographic, and
      social conditions. In the past two decades, Divinopolis, Minas Gerais State,
      Brazil, has exhibited the potential for a disease outbreak, with the appearance
      of CL, and VL cases (human and canine). Hence, this study was initiated to
      monitor public knowledge of the disease. Questionnaires were administered in four
      neighborhoods (Jardim Belvedere, Esplanada, Danilo Passos I and II) where most of
      the human and canine cases have been reported. The analyses demonstrated that
      public knowledge of the disease is sparse and fragmented. A strong perception of
      the dog as the main reservoir was observed. Five veterinary clinics were
      evaluated for the presence of canine VL using serological (RIFI and ELISA) and
      molecular (PCR-RFLP) techniques. This is the first study demonstrating the
      occurrence of Leishmania infantum in Divinopolis, suggesting a possible
      urbanization of VL.

PMID- 22991523
TI  - Sister chromatid exchange in Greenleg Partridge and Polbar hens covered by the
      gene-pool protection program for farm animals in Poland.
AB  - A basic assay that detects genotoxic DNA damage disrupting DNA replication and
      repair mechanisms is the sister chromatid exchange test. The frequency of sister
      chromatid exchanges was analyzed in chromosomes of the following hen breeds:
      Greenleg Partridge and Polbar. Chromosome preparations were obtained from our in
      vitro culture of peripheral blood lymphocytes stained using the fluorescence plus
      Giemsa (FPG) technique. The sister chromatid exchange (SCE)/cell mean of the hens
      under analysis was 7.83 +/- 1.76 (7.22 +/- 1.70 in the Greenleg Partridge and
      8.43 +/- 1.61 in the Polbar population). Statistically significant differences
      were identified between the hen breeds. A higher mean number of SCE/cell was
      observed in the group of hens producing fewer eggs (8.55 +/- 1.51) compared with
      the group with a better egg yield (7.10 +/- 1.65). The differences were
      statistically significant. Additionally, SCE frequency in the first, second, and
      third chromosome was analyzed in detail. The highest number of SCE was observed
      in the first and the lowest in the third chromosome. The SCE distribution in the
      particular regions of the analyzed chromosomes was also studied. The most
      numerous exchanges were observed in the proximal region, followed by the
      interstitial and distal areas.

PMID- 22991524
TI  - Conjugated linoleic acids alleviate the immunosuppression of peripheral blood T
      lymphocytes in broiler chickens exposed to cyclosporin A.
AB  - The immunoregulatory actions of conjugated linoleic acids (CLA) of relevance
      immunosuppression were investigated. To test the hypothesis that CLA ameliorate
      immunosuppression, we developed the immunosuppressive model of peripheral blood T
      lymphocytes in broiler chickens induced by cyclosporin A. Peripheral blood T
      lymphocytes of broiler chickens were cultured with media containing various
      concentrations (25, 50, 100, and 200 MUmol/L) of c9, t11-CLA and t10, c12-CLA to
      investigate the effects of CLA isomers on peripheral blood T lymphocyte
      proliferation, interleukin-2, the activity of phospholipase C, and protein kinase
      C production. Results suggested that CLA alleviated the immunosuppression of T
      lymphocytes in broiler chickens exposed to cyclosporin A through increasing of
      peripheral blood T lymphocyte proliferation and interleukin-2. The 2 CLA isomers
      enhanced T lymphocyte proliferation at low concentration and inhibited T
      lymphocyte proliferation at high concentration. In addition, the effect of c9,
      t11-CLA was better than that of t10, c12-CLA. At the cellular level, the effects
      of CLA on the alleviation of immunosuppression in T lymphocytes are mainly
      attributable to increasing the signaling molecules, such as phospholipase C and
      protein kinase C.

PMID- 22991525
TI  - Prevalence and characteristics of intimin-producing Escherichia coli strains
      isolated from healthy chickens in Korea.
AB  - Virulent Escherichia coli strains have commonly been associated with diarrheal
      illness in humans and animals. Typical enteropathogenic Escherichia coli (EPEC)
      with intimin gene (eaeA) and E. coli adherence factor plasmid, or atypical EPEC
      with only eaeA have been implicated in human cases. In the present study, we
      investigated the prevalence of virulence-associated genes including eaeA in the
      E. coli strains isolated from cloacal specimens of 184 chicken flocks in 7
      provinces in Korea between 2009 and 2010. When 7 virulence genes (VT1, VT2, LT,
      and ST for enterotoxigenic E. coli; eaeA and bfpA for enteropathogenic E. coli;
      and aggR for enteroaggregative E. coli) were screened by multiplex PCR, a total
      of 30 E. coli strains carrying only the eaeA gene were detected from 184 flocks
      that were identified as atypical enteropathogenic Escherichia coli (aEPEC). The
      aEPEC strains were analyzed by eae subtyping, phylogenetic grouping PCR, and
      serotyping. Twelve (40%) of 30 aEPEC strains possessed an eae-beta subtype,
      followed by theta (30%), epsilon (16.7%), and beta1 (13.3%). Eight (26.7%) of 30
      aEPEC strains were designated into the phylogenetic group A. Two (6.7%) and 3
      (10%) aEPEC strains were classified into the phylogenetic group B2 and D,
      respectively. A total of 15 (50%) aEPEC strains were serotyped to groups O24,
      O25, O26, O71, O80, O103, and O157, and the remaining strains were nontypeable.
      In analyzing the genetic diversity among the 30 aEPEC isolates by the pulsed
      field gel electrophoresis method with XbaI-digestion, the pulsed-field gel
      electrophoresis profiling produced 20 different patterns, but isolates within the
      same group did not show clear geographic or breed relationships. Our data
      indicate that healthy chickens may constitute an important natural reservoir of
      aEPEC strains, and suggest that transmission to humans could not be excluded.

PMID- 22991526
TI  - Immunization with outer membrane protein A from Salmonella enterica serovar
      Enteritidis induces humoral immune response but no protection against homologous
      challenge in chickens.
AB  - Vaccination of poultry is one promising strategy to mitigate Salmonella infection
      in poultry and, in turn, humans as well. We evaluated the efficacy of outer
      membrane protein A (OmpA) as a novel vaccine candidate against Salmonella in
      poultry. Native OmpA purified from Salmonella enterica serovar Enteritidis was
      mixed with adjuvant and administered intramuscularly to 41-d-old chicks. The
      vaccinated birds showed no decrease in cecal excretion and tissue colonization
      compared with the unvaccinated birds after oral challenge with 10(9) cfu of the
      homologous strain at 28 d postimmunization. However, this vaccination induced an
      increased level of serum anti-OmpA IgG. Similar results were obtained in the
      replication experiments using a recombinant OmpA with single and double doses.
      For the development of more effective component vaccines for avian salmonellosis,
      the vaccine efficacy of outer membrane proteins other than OmpA and route of
      immunization other than parenteral administration should be evaluated with regard
      to protection and immune responses, including mucosal IgA.

PMID- 22991527
TI  - Development and application of specific polymerase chain reaction assay targeting
      the gyrB gene for rapid detection of Riemerella anatipestifer.
AB  - A pair of PCR primers was designed and synthesized to amplify a gyrB gene
      sequence from Riemerella anatipestifer (RA). A fragment of 194 bp was detected in
      RA-positive isolates, whereas other isolates were negative, which confirmed the
      high specificity of the primers and PCR conditions. As little as 1.6 * 10(4)
      cfu/mL of cultural liquid was required by this method. We compared a 16S rRNA
      sequence-based PCR method and a Biolog bacterial identification system used in
      the detection and identification of suspicious isolates of RA in clinical tests.
      The results showed that the gyrB-based PCR was consistent with the results of the
      Biolog identification system and was more specific. By applying the gyrB-PCR to
      detect RA strains in 56 duck livers, a positive rate of 46% (26/56) was observed,
      whereas the positive rate of 85 throat swabs from clinically healthy ducks was
      11%. Thus, this method could be used for the epidemiological investigation and
      preliminary isolate identification of RA.

PMID- 22991528
TI  - Immunomodulation in young laying hens by dietary folic acid and acute immune
      responses after challenge with Escherichia coli lipopolysaccharide.
AB  - We investigated the effects of dietary folic acid (FA) supplementation on
      immunological parameters in young laying hens under acute conditions of
      lipopolysaccharide (LPS) challenge. Twenty-four Shaver White laying hens at 24 wk
      were fed 2 diets in a completely randomized design. The diets were wheat-soybean
      based, with either 0 or 4 mg of supplemental FA per kilogram of diet. At 32 wk of
      age, 6 hens from each dietary treatment were injected intravenously with 8 mg/kg
      of BW of either LPS or saline. Four hours after injection, blood was collected
      and the hens were euthanized to obtain spleen and cecal tonsils.
      Heterophil:lymphocyte ratio, CD3+, CD4+, CD8+ T cells, and CD4+:CD8+ cells in the
      blood and spleen were not affected by dietary FA. Relative to saline-injected
      hens, LPS-injected hens had fewer (P < 0.05) CD3+, CD4+, CD8+, and CD4+:CD8+
      cells in the blood, and no difference was found in the spleen. Total protein,
      albumin, and globulin were found to be higher (P < 0.05) in FA-supplemented hens
      compared with the control. However, total protein, albumin, and globulins
      decreased (P < 0.05) in the LPS-injected hens compared with the saline control.
      Expression of interleukin (IL)-1beta in cecal tonsils decreased (P < 0.05) in FA
      supplemented hens, but no dietary influence was found on the expression of other
      genes in both the spleen and cecal tonsils. Lipopolysaccharide upregulated (P <
      0.05) expression of IL-10 and interferon (IFN)-gamma in the spleen, and IL-1beta,
      IL-10, and IFN-gamma in the cecal tonsils, whereas the expression of Toll-like
      receptor (TLR)-4 and IL-8 was not influenced by LPS in the spleen and cecal
      tonsils. There was a diet * challenge interaction for total IgG, and cytokines IL
      1beta and IL-18 in the spleen as well as IL-18 in the cecal tonsils. In
      conclusion, there were few interactions of dietary FA and LPS; however, FA
      increased biochemical constituents, enhanced generation of total IgG, as well as
      exhibiting pleoitropic effects in inflammatory responses.

PMID- 22991529
TI  - Dexamethasone triggers lameness associated with necrosis of the proximal tibial
      head and proximal femoral head in broilers.
AB  - Bacterial chondronecrosis with osteomyelitis (BCO) and turkey osteomyelitis
      complex (TOC) are characterized by bacterial infection and necrotic degeneration
      within the tibiae and femora. Stress and immunosuppression have been implicated
      in the pathogenesis of BCO and TOC. Immunosuppressive doses of dexamethasone
      (DEX) trigger high incidences of TOC in turkey poults. The present study was
      conducted to determine if DEX injections or heat stress can trigger BCO and
      lameness in broilers. In 3 independent experiments, broilers were weighed and
      either remained uninjected or received repeated injections of 0.9% saline or DEX
      dissolved in saline (0.45 to 1.5 mg of DEX/kg of BW). Across all 3 experiments,
      the incidences of lameness were 0% for uninjected controls, 0 to 8% in saline
      injected groups, and 24 to 68% in groups injected with 0.9 to 1.5 mg of DEX/kg of
      BW. Growth was inhibited by DEX injections regardless of whether the birds became
      lame or survived. When compared with saline-injected groups, DEX injections
      consistently increased the incidence of severe proximal tibial head necrosis in
      lame birds as well as in survivors. The DEX injections also triggered a subset of
      lesions that are not considered pathognomonic for BCO (for example, avascular
      femoral head necrosis and fatty necrosis of the tibiae). In a fourth experiment,
      repeated episodes of heat stress did not trigger lameness, although the
      subclinical incidence of tibial head necrosis was substantially higher at 28 and
      35 d of age in heat-stressed broilers when compared with broilers reared under
      thermoneutral conditions. Accordingly, stress and immunosuppression must be
      considered contributing factors in the pathogenesis of tibial and femoral lesions
      associated with lameness in broilers. A subset of the lesions triggered by
      repeated DEX injections did not precisely mimic the pathogenesis of BCO in
      broilers, and DEX consistently inhibited growth whereas BCO is associated with
      rapid growth. These caveats must be acknowledged when DEX is used to trigger
      lameness in broilers.

PMID- 22991530
TI  - Molecular cloning, characterization, and expression analysis of the Muscovy duck
      Toll-like receptor 3 (MdTLR3) gene.
AB  - Toll-like receptor 3 (TLR3) is an important membrane-bound receptor for
      recognizing double-stranded RNA in innate immunity. In this study, we described
      the cloning and characterization of the Muscovy duck TLR3 (MdTLR3) gene. The full
      length MdTLR3 cDNA (2,836 bp) encoded a polypeptide of 895 amino acids. The
      deduced amino acid sequence contained 4 main structural domains: a signal
      peptide, an extracellular leucine rich repeats domain, a transmembrane domain,
      and a Toll/IL-1 receptor domain. Quantitative real-time PCR analysis indicated
      that MdTLR3 mRNA was constitutively expressed in all sampled tissues of
      uninfected Muscovy duck except muscle. Expression of MdTLR3 in brain was
      significantly upregulated at 24 h (1.94-fold, P < 0.05), reached a peak at 48 h
      (4.64-fold, P < 0.05), and recovered to normal levels at 72 h postinfection with
      the H5N1 highly pathogenic avian influenza virus. In contrast, MdTLR3 expression
      was downregulated during the test period in spleen and lung. These results
      implicated MdTLR3 was a novel member of the TLR family, which is involved in the
      early stage of antiviral innate immunity.

PMID- 22991531
TI  - Molecular epidemiological survey on aminoglycoside antibiotics-resistant genotype
      and phenotype of avian Escherichia coli in North China.
AB  - Monitoring drug resistance in Escherichia coli is important for prevention and
      treatment of colibacillosis. To choose effective drugs to prevent and control
      avian colibacillosis in North China, we investigated resistance of 205 E. coli
      isolates (from Beijing, Tianjin, inner Mongolia, Shanxi, and Hebei regions) to
      commonly used clinical aminoglycoside antibiotics using a drug susceptibility
      test. The results show that the isolates had varying degrees of resistance to
      kanamycin, gentamicin, streptomycin, amikacin, neomycin, and spectinomycin.
      Particularly, the resistance rates of the former 3 antibiotics exceeded 40%. To
      explore the reasons for wide drug resistance, aminoglycosides modifying enzymes
      (AME) genes, which are important in generation of aminoglycoside resistance, were
      detected by PCR. Of the isolates, 60.98% carried AME genes and 38.05% carried
      commensal multidrug resistance genes. Therefore, resistance of avian E. coli to
      aminoglycoside antibiotics is very serious in North China, perhaps due to the
      existence of resistance genes.

PMID- 22991532
TI  - Effects of feed-borne Fusarium mycotoxins with or without yeast cell wall
      adsorbent on organ weight, serum biochemistry, and immunological parameters of
      broiler chickens.
AB  - The objectives of the present study were to investigate the toxicity of feed
      borne Fusarium mycotoxins on organ weight, serum biochemistry, and immunological
      parameters of broiler chickens and to evaluate the efficacy of yeast cell wall
      adsorbent in preventing mycotoxin-induced adverse effects. In total, 300 one-day
      old vaccinated (Marek's disease and infectious bronchitis) Arbor Acres broiler
      chickens (mixed sex) were randomly divided into 3 treatments (5 repetitions per
      treatment) and fed basal diet and naturally contaminated diets with or without
      yeast cell wall adsorbent. Treatments were control, naturally contaminated diet
      (NCD; aflatoxin, 102.08 mg/kg; zearalenone, 281.92 mg/kg; fumonisin, 5,874.38
      mg/kg; deoxynivalenol, 2,038.96 mg/kg), and NCD + 2 g/kg of yeast cell wall
      adsorbent (NCDD). The test included 2 phases: d 0-21 and d 22-42. At 42 d,
      broilers fed contaminated diets without yeast cell wall adsorbent had higher (P <
      0.05) serum albumin and higher relative weight of liver, bursa of Fabricius, and
      thymus, and greater splenic mRNA expression of IL-1beta and IL-6 at 42 d compared
      with the control, but lower (P < 0.05) serum globulin at 42 d, IgA at 21 d,
      relative weight of spleen at 21 d, antibody titers of Newcastle disease at both
      28 d and 42 d, and splenic mRNA expression of IFN-gamma at 42 d were observed in
      the NCD treatment compared with control. Dietary addition of yeast cell wall
      adsorbent in the NCD treatment showed a positive protection effect on the
      relative weight of the liver and spleen at 21 d, relative weight of the bursa of
      Fabricius and thymus at 42 d, antibody titers of Newcastle disease at both 28 d
      and 42 d, and splenic mRNA expression of IL-1beta, IL-6, and IFN-gamma at 42 d.
      It is suggested that feeding a naturally contaminated diet for 42 d might result
      in a deleterious effect in broiler chickens, and addition of 2 g/kg of yeast cell
      wall enterosorbent can partly neutralize the detrimental effects of the naturally
      contaminated feed.

PMID- 22991533
TI  - Quantification of interferon, interleukin, and Toll-like receptor 7 mRNA in quail
      splenocytes using real-time PCR.
AB  - Japanese quail (Coturnix japonica) are farmed worldwide as poultry. Quail have
      been used as experimental animals in various scientific fields, but their
      immunological characteristics have not been well characterized. In this study, to
      develop a method for analyzing the innate immune response of quail to infectious
      pathogens, we determined the nucleotide sequences of major interleukins (IL) and
      Toll-like receptor (TLR)-7 of quail and developed quantitative real-time PCR
      assays. The nucleotide sequences of quail IL-1beta, IL-4, IL-6, IL-8, IL-10, IL
      12a, IL-12b, IL-13, IL-18, and TLR-7 were determined based on the sequences of
      the chicken genes. Specific primers for each of these genes and previously
      reported interferon (IFN)-alpha, IFN-gamma, and IL-2 genes were designed for
      quantitative real-time PCR. Standard curves for quantification were established
      using serial dilutions of external standard plasmids containing real-time PCR
      products. Then, real-time PCR was performed to monitor the kinetics of quail
      immune-related gene expression induced in splenocytes stimulated with
      concanavalin A. After amplification, the r(2) values of the standard curves for
      all target genes were above 0.980. Melting analysis of real-time PCR revealed
      specific amplification of each gene that could be visualized clearly as a single
      peak of melting temperature in a melt peak chart. These data show that the mRNA
      expressions of quail immune-related genes can be accurately quantified using this
      real-time PCR assay. In this study, we showed the nucleotide sequences of several
      quail cytokine mRNA and constructed the quantitative real-time PCR for quail
      immune-related genes.

PMID- 22991534
TI  - Epidemiological investigation of outbreaks of fowl adenovirus infection in
      commercial chickens in Korea.
AB  - In total, 39 clinical cases of fowl adenoviruses (FAdV) infection in chickens (28
      broiler, 7 native, and 4 layer chickens) between 2007 and 2010 in Korea were
      investigated. The FAdV types 4, 8b, and 11 comprised 18, 9, and 12 clinical
      cases, respectively. All FAdV type 4 cases showed clinical hydropericardium (HPS)
      lesions as well as inclusion body hepatitis (IBH), whereas all FAdV types 8b and
      11 cases exhibited IBH lesions without HPS. All 3 types were detected in broiler
      (9-30 d old) and layer chickens (23-112 d old), whereas most native chickens (14
      65 d old) were affected only by FAdV type 4. Infectious bursal disease virus and
      chicken infectious anemia virus were complications in 51.3% of FAdV cases, with
      mortalities of 55% to <0.1%. Chicken infectious anemia virus was detected in all
      native chicken cases. These results indicate that preventive measures against
      FAdV infection and immunosuppressive diseases on poultry farms should be
      implemented.

PMID- 22991535
TI  - Development of FPV140 antigen-specific ELISA differentiating fowlpox virus
      isolates from all other viral pathogens of avian origin.
AB  - The FPV140 gene encodes an envelope protein of fowlpox virus (FPV). In this
      study, the FPV140 gene of FPV Chinese isolate HH2008 was cloned and the
      comparison of its sequence with other FPV isolates showed it to be highly
      conserved across all FPV isolates. A recombinant plasmid pET-FPV140 carrying
      FPV140 gene was constructed and transformed into Escherichia coli. The optimal
      expression condition for the FPV140 gene was developed and purified FPV140
      recombinant protein was used to produce rabbit polyclonal antibody. An indirect
      ELISA using this anti-FPV140 polyclonal antibody was capable of distinguishing
      avian FPV isolates from other common avian pathogens such as mycoplasma
      gallisepticum, infectious laryngotracheitis virus, avian influenza virus,
      infectious bursal disease virus, and avian infectious bronchitis virus. This
      ELISA will serve as a useful diagnostic tool for the detection of FPV in clinical
      samples.

PMID- 22991536
TI  - Polymorphisms of chicken Toll-like receptors 4, 15, and 21 in different breeds.
AB  - Toll-like receptors (TLR) mediate immune responses via the recognition of
      pathogen-associated molecular patterns, thus playing important roles in host
      defense. Among the chicken (Ch) TLR family, ChTLR1, 2, 4, 15, and 21 were shown
      to recognize bacterial components. In our earlier study, we reported
      polymorphisms of TLR1, 2, and 5. In the present study, we cloned TLR4, 15, and 21
      genes from different chicken breeds and analyzed their sequences. We identified 9
      amino acid polymorphism sites in ChTLR4 with 8 extracellular domain sites and 1
      site in the cytoplasmic domain, 15 amino acid polymorphism sites in ChTLR15 with
      14 extracellular domain sites and 1 site in the cytoplasmic domain, and 7 amino
      acid polymorphism sites in ChTLR21 with 5 extracellular domain sites and 2 sites
      in the cytoplasmic domain. These results demonstrate that ChTLR genes are
      polymorphic among different avian breeds, suggesting a varied resistance across
      numerous chicken breeds. This information might help improve chicken health by
      breeding and vaccination.

PMID- 22991537
TI  - Effect of intranasal administration of Lactobacillus fermentum CJL-112 on
      horizontal transmission of influenza virus in chickens.
AB  - The aim of this study was to determine whether intranasal administration of
      Lactobacillus sp. could prevent horizontal transmission of H9N2 avian influenza
      virus (AIV) in specific-pathogen-free chickens. Three-week-old chickens received
      500 MUL of 1.5 * 10(9) cfu of Lactobacillus fermentum CJL-112 strain (CJL)
      intranasally for 7 d before and 14 d after a challenge. Challenged chickens, each
      inoculated with H9N2 AIV, were kept in either direct or indirect contact with
      naive chickens, and morbidity and viral shedding were monitored. We demonstrated
      that the intranasal administration of CJL significantly decreased the number of
      chickens with viral shedding from the gastrointestinal tract in the indirect
      contact chickens (P < 0.001) and also significantly reduced viral shedding from
      the respiratory tract in the challenged (P < 0.05) and the direct contact
      chickens (P < 0.001) than those in the control group. Hence, the use of this
      lactobacilli strain may constitute a novel and effectively plausible alternative
      to prevent and control H9N2 AIV infection in chickens.

PMID- 22991538
TI  - Consequences of phosphorus interactions with calcium, phytase, and
      cholecalciferol on zootechnical performance and mineral retention in broiler
      chickens.
AB  - The objective was to determine the effect of calcium (Ca), total phosphorus
      (Ptot), cholecalciferol, and phytase level in the diet on the performance, tibia
      ash percentage, and Ca and P retention in broilers until slaughter age. Broilers
      were randomly assigned to 12 treatments, each with 6 replicates, comprising 3
      diets differing in Ca and P level: 1) normal Ca and Ptot level (NN); 2) normal Ca
      and low Ptot level (NL), 3) low Ca and Ptot level (LL). Broilers were also given
      2 levels of cholecalciferol and 2 levels of phytase. The normal levels of Ca and
      Ptot for the starter, grower, and finisher phases were 0.90, 0.82, 0.74% and
      0.67, 0.62, 0.57%, respectively. The low Ca and Ptot levels for the 3 phases were
      0.67, 0.60, 0.52% and 0.57, 0.51, 0.46%, respectively. Broilers of the NL
      treatment obtained the lowest BW, whereas BW of the NN and LL groups were
      comparable. Cholecalciferol significantly affected the BW, with differences up to
      2.6 and 1.2% for the starter and grower phases, respectively. The highest
      cholecalciferol effect was found in combination with the NN treatment. The
      percentage of retained Ca increased from 33% to 41% and 48% when the imbalanced
      diet was replaced by the NN and LL balanced diets, respectively. P release from
      phytate was 64 and 67% for the NL and LL diets, respectively. Phytase and
      cholecalciferol had significantly favorable effects on retention values but these
      effects were dependent on Ca and Ptot levels and their ratio. In conclusion, both
      diets with the balanced Ca/Ptot ratio resulted in the best performance, highest
      tibia ash percentage and P release from phytate. A reduction of the Aviagen
      (2009) recommended P requirements by 25 to 30% and Ca by 15 to 20% over the
      various phases did not negatively affect performance, bone development, and
      improved Ca and Ptot retention. The effects of supplementing cholecalciferol and
      phytase were additive but not significant and no synergism between both was
      present.

PMID- 22991539
TI  - Effects of nano-selenium on performance, meat quality, immune function, oxidation
      resistance, and tissue selenium content in broilers.
AB  - This study was conducted to investigate the effect of nano-selenium (nano-Se) on
      performance, meat quality, immune function, oxidation resistance, and tissue
      selenium content in broilers. A total of five hundred forty 1-d-old male Arbor
      Acres broilers were randomly allotted to 1 of 5 treatments with each treatment
      being applied to 6 replicates of 18 chicks. The 5 treatments consisted of corn
      soybean meal-based diets supplemented with 0.0, 0.3, 0.5, 1.0, or 2.0 mg/kg of
      nano-Se. The selenium content of the unsupplemented control diet was 0.09 mg/kg
      for the starter phase (0 to 21 d) and 0.08 mg/kg for the grower phase (22 to 42
      d). There were no significant differences (P > 0.05) in performance, meat color,
      or immune organ index (thymus, bursa, and spleen) due to supplementation with
      nano-Se. On d 42, a significant quadratic effect of nano-Se was observed on
      glutathione peroxidase activity, free radical inhibition, contents of IgM,
      glutathione, and malondialdehyde in serum, on glutathione peroxidase activity,
      free radical inhibition in liver, and on glutathione peroxidase activity in
      muscle, with birds fed 0.30 mg/kg of nano-Se exhibiting the best effect and birds
      fed 2.0 mg/kg of nano-Se showing the worst effect on these parameters. Liver and
      muscle selenium content increased linearly and quadratically as the dietary nano
      Se level increased (P < 0.01), and reached the highest value when 2.0 mg/kg of
      nano-Se was fed. Based on a consideration of all experiment indexes, 0.3 to 0.5
      mg/kg is suggested to be the optimum level of supplementation of nano-Se, and the
      maximum supplementation of nano-Se could not be more than 1.0 mg/kg in broilers.

PMID- 22991540
TI  - Evaluation of near-infrared reflectance spectroscopy (NIRS) techniques for total
      and phytate phosphorus of common poultry feed ingredients.
AB  - The purpose of this study was to determine the feasibility of estimating the
      total and phytate P content of common poultry feed ingredients by near-infrared
      reflectance spectroscopy (NIRS). Samples of 8 plant-origin feedstuffs were
      collected from poultry producers in the USA and Canada during the summer of 2009:
      corn (133), soybean meal (114), corn distillers dried grains with solubles (DDGS;
      89), bakery by-product meal (95), wheat (22), wheat middlings (31), canola meal
      (21), and wheat shorts (15). The samples were assayed by standard wet chemical
      techniques for total and phytate P contents. There was considerable variation
      found in most of the ingredient components. The average values for the laboratory
      determinations versus NIRS predictions were all within 0.030 for total phosphorus
      and 0.012 for phytate P. For phytate P, the magnitude of the standard errors of
      the predictions ranged from 0.009% for soybean meal to 0.012% for canola meal.
      These values may be sufficiently precise for nutritionists to use the NIRS
      predictions to estimate how much of the P in their ingredients is not available
      to the birds. For total P, the magnitude of the standard errors of the
      predictions ranged from 0.027% for corn DDGS to 0.142% for wheat middlings. In
      general, total P predictions by NIRS were not generally sufficiently precise for
      most nutritionists to use in feed formulation. Decision making may be quite easy
      in using NIRS estimates for the phytate P content of bakery by-product meal [R(2)
      = 0.89 for predicted = f (determined)] but not for the total P content of soybean
      meal (R(2) = 0.03). It is concluded that precise estimates of phytate P through
      NIRS should allow nutritionists for more efficient formulate and mix feed,
      lowering feed costs and reducing the amount of residual polluting phosphorus in
      poultry excreta.

PMID- 22991541
TI  - Protein expression in pectoral skeletal muscle of chickens as influenced by
      dietary methionine.
AB  - Effects of dietary methionine (Met) on pectoralis muscle development and the
      effect that Met as a nutritional substrate has on protein expression of skeletal
      muscle cells of pectoralis muscle of chickens were evaluated in this study.
      Broiler chickens received a common pretest diet up to 21 d of age and were
      subsequently fed either a low (LM) or high Met (HM) diet (0.41 vs. 0.51% of diet)
      from 21 to 42 d of age. Dietary deficiency was shown in vivo judging by the
      depression in breast meat weight and yield when broilers were fed the LM diet.
      Global protein expression was analyzed by quantitative high-performance liquid
      chromatography nanospray ionization tandem mass spectrometry. Up- and
      downregulated proteins were analyzed via Ingenuity Pathways Analysis to identify
      the metabolic pathways affected. Four canonical pathways related to muscle
      development were identified as being differentially regulated between LM- and HM
      fed chickens. These pathways included the citrate cycle and calcium, actin
      cytoskeleton, and clathrin-mediated endocytosis signaling. The HM diet may have
      allowed for increased muscle growth by an increased availability of nutrients to
      muscle cells. Although the Met supplementation was associated with enhanced
      breast muscle growth, contraction fiber concentrations in muscles decreased and
      were associated with a lower calcium transportation rate and sensitivity and with
      a lower energy supply. It is further suggested that increased muscle protein
      deposition, that was induced by Met supplementation, may have been largely due to
      sarcoplasmic rather myofibrillar hypertrophy.

PMID- 22991542
TI  - Apparent metabolizable energy and apparent ileal amino acid digestibility of low
      and ultra-low oligosaccharide soybean meals fed to broiler chickens.
AB  - Four experiments were conducted using 1,992 Ross * Ross 708 male broilers to
      determine AME(n) and apparent ileal amino acid digestibility (AIAAD) of low
      oligosaccharide (LOSBM), ultra-low oligosaccharide (ULSBM), and control soybean
      meal (CSBM) fed to broilers from 20 to 31 d of age. An AME(n) assay was conducted
      in experiments 1 and 2, whereas AIAAD was determined in experiments 3 and 4.
      Chicks were randomly assigned to 3, 4, 2, or 3 dietary treatments, respectively,
      for experiments 1, 2, 3, or 4. The additional treatment in experiments 2 and 4
      was to evaluate ULSBM. In the AME(n) assays, treatments were fed from 20 to 29 d
      of age and a 48-h excreta collection period was conducted from 27 to 29 d of age.
      Treatment 1 consisted of a basal diet and treatments 2, 3, and 4 consisted of 70%
      of the basal diet plus 30% CSBM, LOSBM, or ULSBM, respectively. The difference
      method was used to determine AME(n) utilizing an N correction factor to account
      for N retention. To determine AIAAD, broilers were fed semi-purified diets with
      CSBM, LOSBM, or ULSBM as the sole source of amino acids (AA) from 26 to 31 d of
      age with digesta collection occurring at 31 d of age. In experiment 1, LOSBM had
      194 kcal/kg more AME(n) compared with CSBM (P = 0.011). Apparent ME(n) value of
      LOSBM was 141 and 134 kcal/kg higher (P = 0.012) compared with CSBM and ULSBM,
      respectively, in experiment 2. Digestible Lys, Met, Ile, and Val concentrations
      were higher (P < 0.001) for LOSBM vs. CSBM in experiment 3 even though
      digestibility coefficients were lower (P < 0.001) for LOSBM. In experiment 4,
      higher (P < 0.001) concentrations of digestible Met, Lys, Thr, Val, and Ile were
      observed for ULSBM and LOSBM compared with CSBM. In conclusion, genetically
      selected soybean meals with reduced stachyose and raffinose concentrations had
      higher AME(n) and AIAAD values compared with CSBM.

PMID- 22991543
TI  - Factors that affect the nutritive value of canola meal for poultry.
AB  - This article reviews the factors affecting the nutritive value of canola meal
      (CM), including glucosinolates, sinapine, phytic acid, tannins, dietary fiber,
      and electrolyte balance. It also addresses the means of improving the nutritive
      value of CM throughout seed dehulling, development of low-fiber canola, or
      application of feed enzymes. Over the years, the glucosinolate content of canola
      has been declining steadily and is now only about one-twelfth of that of the
      older high-glucosinolate rapeseed (that is, 10 vs. 120 MUmol/g). Therefore, the
      rations for broilers or laying hens could now contain 20% of CM without producing
      any adverse effects. Tannins are of lesser importance due to their presence in
      the hull fraction and thus low water solubility. Sinapine has been implicated
      with the production of a "fishy" taint in brown-shelled eggs, which results from
      a genetic defect among the strain of Rhode Island Red laying hens. The White
      Leghorns have been reported not to be affected. Although lower in protein, CM
      compares favorably with soybean meal with regard to amino acid content. Because
      CM contains more methionine and cysteine but less lysine, both meals tend to
      complement each other when used together in poultry diets. Canola meal is low in
      arginine (Arg) which could be of importance when introducing CM to broiler diets
      at high inclusion rates. The Arg content of CM is approximately two-thirds of
      that of soybean meal. Chickens fail to synthesize Arg and are highly dependent on
      dietary sources for this amino acid. Supplementation of Arg to CM-based diets has
      been shown to partly restore the growth performance. Dietary cation-anion
      difference in CM is also less than optimal due to the high sulfur and low
      potassium contents. Seed dehulling has not been very successful due to excessive
      fineness and thus difficulties with percolation of the miscella through the cake.
      Development of low-fiber, yellow-seeded canola and the use of enzymes have proven
      to increase the energy utilization and the nutritive value of CM for poultry.

PMID- 22991544
TI  - Gene expression in breast muscle associated with feed efficiency in a single male
      broiler line using a chicken 44K microarray. II. Differentially expressed focus
      genes.
AB  - Global RNA expression in breast muscle obtained from a male broiler line
      phenotyped for high or low feed efficiency (FE) was investigated using microarray
      analysis. Microarray procedures and validation were reported previously. By using
      an overlay function of a software program (Ingenuity Pathway Analysis, IPA) in
      which canonical pathways are projected onto a set of genes, a subset of 27
      differentially expressed focus genes were identified. Focus genes that were
      upregulated in the high FE phenotype were associated with important signal
      transduction pathways (Jnk, G-coupled, and retinoic acid) or in sensing cell
      energy status and stimulating energy production that would likely enhance growth
      and development of muscle tissue. In contrast, focus genes that were upregulated
      in the low FE muscle phenotype were associated with cytoskeletal architecture
      (e.g., actin-myosin filaments), fatty acid oxidation, growth factors, or ones
      that would likely be induced in response to oxidative stress. The results of this
      study provide additional information on gene expression and the cellular basis of
      feed efficiency in broilers.

PMID- 22991545
TI  - Comparison and characteristics of the formation of different adipose tissues in
      ducks during early growth.
AB  - The objective of the current research was to investigate the pattern of
      subcutaneous adipose tissue growth during Peking duck (Anas platyrhynchos) early
      development and to determine the reasons for regional differences. The
      morphological characteristics in 5 regions of subcutaneous tissue, including the
      neck area (NSF), chest area (CSF), lower abdomen area (ASF), back area (BSF), and
      leg area (LSF), were analyzed by comparing the morphology of the sections,
      adipocyte volume and number, and lipid content from wk 1 to 8. Moreover, the mRNA
      expression of several molecular marker genes, including 47-kDa tail interacting
      protein (TIP47), adipose differentiation-related protein (ADRP), and perilipin,
      were detected from wk 1 to 8 using quantitative real-time PCR. Our results
      revealed that the average cell number declined greatly as fattening proceeded
      (except in the NSF) and changed very little after wk 4 in all 5 regions. In
      contrast, the average cell volume and triglyceride content per cell increased
      gradually during early duck growth. The BSF and LSF lipid content had a different
      pattern of change than the other regions. The NSF, CSF, and ASF regions had the
      highest lipid content values at all stages, the BSF was intermediate, and the LSF
      was the lowest at all weeks except wk 3. The highest TIP47 expression level was
      found in the NSF from wk 1 to 2 and BSF at wk 1. The relative expression level of
      TIP47 was higher in the CSF than in the ASF and BSF at wk 4, and was higher in
      the NSF than in the ASF at wk 6. The highest levels of ADRP and perilipin were
      detected in the LSF. These results suggest that a combination of adipocyte
      hyperplasia and hypertrophy is mainly responsible for the development of duck
      adipose tissue before wk 4, after which adipose expansion is accomplished by
      adipocyte hypertrophy only. Adipocyte hyperplastic and hypertrophic capacity, fat
      storage capacity, and metabolic activity may be partial explanations for the
      regional differences during duck growth.

PMID- 22991546
TI  - Lipoprotein metabolism differs between Marek's disease susceptible and resistant
      chickens.
AB  - Marek's disease (MD) is a lymphoproliferative disease of chickens caused by MD
      virus and has an important impact on the poultry industry worldwide. There have
      been reports showing different physiological characteristics between MD
      susceptible and resistant chickens. However, little is known about whether there
      are differences in lipid metabolism between MD susceptible and resistant lines of
      chickens. In this study, we examined the BW and the weight of tissues (abdominal
      fat, breast muscle with bone, leg muscle with bone, liver, and heart), the
      lipoprotein-cholesterol concentrations and distributions, and the plasma and
      tissue levels of adiponectin and its receptors in the highly resistant and
      susceptible lines during chicken growth. Our data showed that the increase in
      total cholesterol during growth was mainly due to the elevation of cholesterol in
      the low-density/very low-density lipoprotein fraction in MD susceptible chickens,
      whereas the increase of total cholesterol was mainly attributable to the increase
      in high-density lipoprotein-cholesterol in MD resistant chickens. Meanwhile, the
      MD resistant line appeared to have increased plasma adiponectin levels compared
      with MD susceptible chickens during growth. Taken together, our data suggested
      that lipoprotein-cholesterol and adiponectin metabolism are different between MD
      susceptible and resistant chickens.

PMID- 22991547
TI  - Effect of protein, probiotic, and symbiotic supplementation on serum biological
      health markers of molted layers.
AB  - Dietary zinc was used to induce molt in 200 White Leghorn birds in caged housing
      at the age of 70 wk. The birds were equally and randomly allocated to 4 groups
      each of 50 birds as G1 (control; CP 16%, no supplement), G2 (CP 18%, no other
      supplement), G3 (CP 16%, symbiotic Perfectin: 85 mg*L(-1) in drinking water
      daily), and G4 (CP 16%, probiotic Protexin: 85 mg*L(-1) in drinking water daily)
      after the completion of molt. The sampling was conducted 3 times at 5%
      production, peak production, and end of production with 15 birds being killed at
      each sampling from each group to collect the blood for harvesting of serum. Serum
      health markers including total oxidant status, total antioxidant capacity,
      homocysteine concentration, and paraoxonase, arylesterase, and ceruloplasmin
      activity were determined by the prescribed assays. The overall total antioxidant
      capacity was increased, whereas total oxidant status and homocysteine
      concentrations were reduced significantly (P <= 0.01) in all the supplemented
      groups compared with the control. The paraoxonase and ceruloplasmin activity were
      enhanced (P <= 0.01) in the supplemented groups compared with the control, and
      arylesterase activity was increased (P <= 0.01) in only G2 compared with the
      other groups. Although protein supplementation significantly reduced the
      oxidative stress, supplementation with symbiotic and probiotic also improved the
      health status by decreasing the oxidative stress in the birds.

PMID- 22991548
TI  - Bone characteristics of late-term embryonic and hatchling broilers: bone
      development under extreme growth rate.
AB  - The development of broilers is an extreme example of rapid growth, increasing in
      weight from 40 g at hatch to 2,000 g 5 to 6 wk later. Such rapid growth requires
      a correspondingly fast development of the skeleton. Bone development is a
      genetically programmed process that is modified by epigenetic factors, mainly
      muscle-induced stresses and strains. In this study, we describe the temporal
      changes in bone morphology and material properties during the prehatch period
      [embryonic day (E) 14, E17, E19, E21] and posthatch d 3 and 7. The bones were
      examined for their weight, length, ash content, mechanical properties, and
      cortical structure. We show that the cross-sectional shape of the tibia and femur
      changes during the examination period from circular to elliptical. Additionally,
      the changes in bone properties are time-dependent and nonuniform: from E14 to E17
      and from d 3 to 7, fast bone growth was noted, with major increases in both
      mechanical properties (stiffness, ultimate load, and energy to fracture) and
      geometric properties (cross-sectional area and thickness, medullary area, and
      moment of inertia). On the other hand, during the last days of incubation, most
      mechanical and geometric properties remain unchanged or even decrease. The
      reasons for this finding may relate to the hatching process but also to mineral
      shortage during the last days of incubation. This study leads to better
      understanding of bone development in ovo and posthatch in fast-growing broilers.

PMID- 22991549
TI  - Validation of a spectrophotometer-based method for estimating daily sperm
      production and deferent duct transit.
AB  - The objectives of the present work were 3-fold. First, a new method for
      estimating daily sperm production was validated. This method, in turn, was used
      to evaluate testis output as well as deferent duct throughput. Next, this
      analytical approach was evaluated in 2 experiments. The first experiment compared
      left and right reproductive tracts within roosters. The second experiment
      compared reproductive tract throughput in roosters from low and high sperm
      mobility lines. Standard curves were constructed from which unknown
      concentrations of sperm cells and sperm nuclei could be predicted from observed
      absorbance. In each case, the independent variable was based upon hemacytometer
      counts, and absorbance was a linear function of concentration. Reproductive
      tracts were excised, semen recovered from each duct, and the extragonadal sperm
      reserve determined by multiplying volume by sperm cell concentration. Testicular
      sperm nuclei were procured by homogenization of a whole testis, overlaying a 20
      mL volume of homogenate upon 15% (wt/vol) Accudenz (Accurate Chemical and
      Scientific Corporation, Westbury, NY), and then washing nuclei by centrifugation
      through the Accudenz layer. Daily sperm production was determined by dividing the
      predicted number of sperm nuclei within the homogenate by 4.5 d (i.e., the time
      sperm with elongated nuclei spend within the testis). Sperm transit through the
      deferent duct was estimated by dividing the extragonadal reserve by daily sperm
      production. Neither the efficiency of sperm production (sperm per gram of
      testicular parenchyma per day) nor deferent duct transit differed between left
      and right reproductive tracts (P > 0.05). Whereas efficiency of sperm production
      did not differ (P > 0.05) between low and high sperm mobility lines, deferent
      duct transit differed between lines (P < 0.001). On average, this process
      required 2.2 and 1.0 d for low and high lines, respectively. In summary, we
      developed and then tested a method for quantifying male reproductive tract
      throughput. This method makes the study of semen production amenable to systems
      biology.

PMID- 22991550
TI  - Effect of selection for commercially productive traits on the plasticity of
      cardiovascular regulation in chicken breeds during embryonic development.
AB  - Domesticated animal breeds have experienced profound anatomical and physiological
      changes as a result of human-driven genetic selection. In poultry, this selection
      process has resulted in many distinct phenotypes from the ancestral bird, the Red
      Junglefowl. Growth rate and egg-laying capacity are 2 traits that have been
      commercially prioritized, and this has resulted in a fast-growth breed, the
      broiler, and a prolific egg layer, the White Leghorn. In this study, we
      investigated basic cardiovascular physiology in these 3 breeds at 90% of
      incubation. We aimed to identify breed-specific features of arterial blood
      pressure and heart rate as well as the physiological mechanisms regulating them.
      Specifically, we investigated mechanisms mediated by the autonomic nervous system
      by means of cholinergic and adrenergic receptors. Our overriding hypothesis was
      that selection for rapid growth would require an acceleration of heart rate and
      arterial pressure development in broilers compared with White Leghorns and the
      ancestral breed. The embryonic broiler is characterized by resting relative
      hypertensive bradycardia, whereas the White Leghorn is hypotensive. All 3 breeds
      maintained resting arterial pressure and heart rate via a similar beta- and alpha
      adrenergic receptor tone; however, cholinergic tone on heart rate was absent in
      the embryonic White Leghorn. Each breed responded differently to incubation in
      chronic hypoxic conditions (14% O(2)). White Leghorn relied on augmenting
      cholinergic heart rate tone, and broilers relied on reducing beta-adrenergic tone
      on pressure. We concluded that selection for rapid growth shifts cardiovascular
      regulatory plasticity to emphasize mechanisms that modulate pressure, and that
      selection for egg-laying capacity emphasizes mechanisms that modulate heart rate.

PMID- 22991551
TI  - Vascular density, hypoxia inducible factor, vascular endothelial growth factor,
      and its receptor expression in the chorioallantois of relatively normoxic and
      hypoxic chicken embryos, at 6 and 7 days of incubation, and corresponding weight
      values.
AB  - The weight of 6- and 7-d-old chicken embryos and their chorioallantoic membrane
      (CAM), vascular density, protein immunoexpression, and mRNA of hypoxia inducible
      factor 2 (HIF-2alpha), vascular endothelial growth factor (VEGF-A), and its type
      receptor 2 (FLK-1) in the CAM were compared in subjects incubated at 2 different
      altitudes: 355 and 1,378 m above sea level (masl) in Colombia. A difference was
      not found when comparing the weight of CAM and embryos incubated at 355 masl with
      those incubated at 1,378 masl on d 6 and 7 of incubation (P > 0.05). Higher
      vascular density in CAM (P < 0.05), percentage of cells immunoexpressing HIF
      2alpha and FLK-1 in the CAM (P < 0.05), and relative expression of HIF-2alpha and
      FLK-1 mRNA in the CAM (P < 0.05 and P < 0.01, respectively) were encountered in
      embryos incubated at 1,378 masl compared with those incubated at 355 masl, but
      only on d 6. Percentages of cells immunoexpressing VEGF-A and relative expression
      of VEGF-A mRNA in the CAM values were not different when considering altitude and
      age (P > 0.05). Relative hypoxia (1,378 masl) appears to affect HIF-2alpha and
      FLK-1 expression in CAM of 6-d-old chicken embryos, and this change in expression
      results in increased vascular development in CAM on this day. At hatching,
      chickens between treatments differed in their BW (P < 0.0001). The lack of
      differences in findings on d 7 could be due to morphological, physiological, and
      molecular events occurring at this time.

PMID- 22991552
TI  - Comparison of blastoderm traits from 2 lines of broilers before and after egg
      storage and incubation.
AB  - We examined the impact of egg storage on the hatchability of eggs from 2 lines (A
      and B) of commercial broiler breeders with known differences in fertility (line B
      slightly higher) and hatchability following egg storage (line A slightly lower).
      Eggs from both lines were stored in a 16 degrees C room for 3 to 4, 10 to 12, and
      17 d, the blastoderms were isolated, evaluated, and statistically compared. No
      significant interactions (line * duration of storage) were observed in the
      following traits: blastoderm diameter, total and percentage of viable
      blastodermal cells, stage of blastoderm development, and embryo weight and stage
      of development after 7 d of incubation. However, significant differences were
      observed when comparing line averages across storage treatments (diameter and
      total number of blastodermal cells) and storage treatment averages across lines
      (percentage of viable cells, and embryo weight and stages following incubation).
      To ascertain the basis for the observed differences in fertility, perivitelline
      sperm-hole numbers were determined in eggs within 72 h of lay (3 to 4 d storage
      group). Eggs from line B had a significantly higher number of eggs having greater
      numbers of sperm holes than eggs from line A. It is concluded that no single
      blastoderm trait or combination of traits can be definitively associated with the
      inter-line differences in hatchability following storage of eggs. Alternatively,
      differences in PVL sperm-hole counts between lines may be associated with the
      reported differences in fertility between the 2 lines.

PMID- 22991553
TI  - Irradiation of shell egg on the physicochemical and functional properties of
      liquid egg white.
AB  - This study was aimed at determining the effect of irradiation of shell eggs on
      the physiochemical and functional properties of liquid egg white during storage.
      Color and textural parameters of irradiated liquid egg white after cooking were
      also determined. Shell eggs were irradiated at 0, 2.5, 5, or 10 kGy using a
      linear accelerator. Egg white was separated from yolk and stored in at 4 degrees
      C up to 14 d. Viscosity, pH, turbidity, foaming properties, color, and volatile
      profile of liquid egg white, and color and texture properties of cooked egg white
      were determined at 0, 7, and 14 d of storage. Irradiation increased the turbidity
      but decreased viscosity of liquid egg white. Foaming capacity and foam stability
      were not affected by irradiation at lower dose (2.5 kGy), but were deteriorated
      at higher doses (>=5.0 kGy) of irradiation. Sulfur-containing volatiles were
      generated by irradiation and their amounts increased as the irradiation dose
      increased. However, the sulfur volatiles disappeared during storage under aerobic
      conditions. Lightness (L* value) and yellowness (b* value) decreased, but
      greenness (-a* value) increased in cooked egg white in irradiation dose-dependent
      manners. All textural parameters (hardness, adhesiveness, cohesiveness,
      chewiness, and resilience) of cooked egg white increased as the irradiation dose
      increased, but those changes were marginal. Our results indicated that
      irradiation of shell egg at lower doses (up to 2.5 kGy) had little negative
      impact on the physiochemical and functional properties of liquid egg white, but
      can improve the efficiency of egg processing due to its viscosity-lowering
      effect. Therefore, irradiation of shell eggs at the lower doses has high
      potential to be used by the egg processing industry to improve the safety of
      liquid egg without compromising its quality.

PMID- 22991554
TI  - Dynamic and static shell properties of white and brown shell eggs exposed to
      modified pressure microcrack detection technology.
AB  - Dynamic and static shell properties of eggs provide important insight to egg
      quality. Understanding how processing and handling procedures affect both dynamic
      and static shell properties can enhance the safety and quality of eggs reaching
      the consumer. A study was conducted to determine if dynamic shell properties were
      altered due to modified pressure microcrack detection technology exposure in
      brown and white shell eggs. Three replicates of 100 eggs each of brown and white
      retail shell eggs were conducted. Dynamic stiffness (K(dyn)) and egg weight were
      monitored immediately before and after microcrack detection. No changes in K(dyn)
      or egg weight were detected for either shell color. Static compression shell
      strength and deformation were subsequently monitored and a correlation analysis
      conducted. A strong correlation (R(2) = 0.53; P < 0.0001) between K(dyn) and
      static compression shell strength was seen for extra large white shell eggs. A
      smaller (R(2) = 0.31; P < 0.0001) correlation was found for large brown eggs. The
      use of modified pressure microcrack detection technology did not affect shell
      dynamic properties.

PMID- 22991555
TI  - Effects of rigor state, thawing temperature, and processing on the
      physicochemical properties of frozen duck breast muscle.
AB  - The objectives of this study were to evaluate effects of rigor state, thawing
      temperature, and processing on the physicochemical properties of intact frozen
      duck breast muscle and homogenates prepared with the frozen-thawed muscles.
      Prerigor breast muscle was frozen at -25 degrees C and thawed at 4 and 15 degrees
      C, and the physicochemical properties of duck breast frozen prerigor compared
      with those in frozen postrigor and 4 degrees C chilled postrigor muscles. The
      homogenates prepared with duck breast frozen prerigor showed similar
      physicochemical properties as the frozen-thawed postrigor muscle homogenate. The
      thawing temperature did not affect the physicochemical properties of homogenates
      prepared with duck breast muscle frozen prerigor. Also, no significant
      differences (P > 0.05) in the ultimate pH value and color parameters were
      observed among the frozen-thawed treatments despite the differences in rigor
      state and thawing temperature. However, a higher thawing temperature of the
      intact frozen prerigor muscle resulted in an increase in thawing loss and shear
      force due to excessive muscle shortening. In this study, the intact duck breast
      that has undergone thaw-rigor showed main problems associated with thaw-rigor,
      such as higher thawing loss and shear force, regardless of thawing temperature.
      However, the processing (grinding and salting) decreased the difference in
      physicochemical properties due to rigor state before freezing and thawing
      temperature. Therefore, the frozen-thawed duck breast muscle used to manufacture
      ground-type meat product may be frozen before rigor onset.

PMID- 22991556
TI  - A comparative study of culture methods and polymerase chain reaction for
      Salmonella detection in egg content.
AB  - The present work compared 2 culture methods and a PCR assay applied with 2
      enrichment methods for the detection of motile and nonmotile Salmonella strains
      using artificially contaminated egg content. The specificity (Sp) was 1 in all
      methods. The sensitivity (Se), accuracy (Ac), positive predictive value (PPV),
      and negative predictive value (NPV) were 1 in both culture methods for motile and
      nonmotile strains. In reference to the PCR methods, Se and PPV were between 0 and
      1, whereas Ac and NPV were between 0.14 and 1. The detection level of motile and
      nonmotile strains was 5 to 54 cfu per 25 mL for both culture methods, but some
      strains could not be detected by the PCR methods. Extending incubation time of
      the enrichment medium to 5 d in the tetrathionate broth (TT), and Muller
      Kauffmann tetrathionate-novobiocin broth (MKTTn) methods did not improve the
      isolation rates. All selective plating media did not show any statistical
      differences in the parameters of performance studied. Kappa coefficients showed
      that there was an excellent agreement between the bacteriological methods for all
      Salmonella strains. The agreement was very good and good between the PCR methods,
      for motile and nonmotile strains, respectively. However, there was a poor
      agreement when the PCR and bacteriological methods were compared for motile and
      nonmotile Salmonella strains. The TT and MKTTn methods are similar in terms of
      Ac, Se, Sp, PPV, and NPV for different Salmonella strains in egg content. The use
      of the PCR method cannot improve the same parameters, described before, in this
      matrix. So, further studies are needed to improve the performance parameters and
      limit of detection in egg content for the PCR methods, so that test can be used
      in poultry and food industry.

PMID- 22991557
TI  - Influence of growth rate on the occurrence of white striping in broiler breast
      fillets.
AB  - White striping refers to the occurrence of different degrees of white striations
      on broiler breast fillets and thighs of larger broilers, yet little is known
      about its causes. Thus, the objective of the study was to estimate the occurrence
      of normal (NORM), moderate (MOD), and severe (SEV) degrees of white striping with
      respect to the growth rate of broilers and to compare their proximate composition
      without the confounding effect of diet. Straight-run 1-d-old chicks (n = 280)
      were randomly assigned to either a low- (LED) or high-energy (HED) diet (5
      replicates of 28 birds/dietary treatment). Birds were processed at 54 d of age,
      and live weight, deboned fillet weight, and occurrence of white striping were
      recorded. As expected, birds fed the HED had lower (P < 0.05) feed conversion
      ratios than birds fed LED (2.08 vs. 2.28). Also, HED-fed birds had heavier P <
      0.05) live and fillet weights when compared with the LED-fed birds. A greater (P
      < 0.05) percentage of breast fillets from LED-fed birds were scored NORM, whereas
      HED-fed birds produced a greater (P < 0.05) percentage of SEV fillets. Fillet
      weight and yield (percent of live weight) increased (P < 0.05) as the degree of
      white striping increased from NORM to SEV. Additionally, NORM fillets had greater
      (P < 0.05) lipid and lower (P < 0.05) protein content when compared with SEV
      fillets. Also, NORM fillets had greater (P < 0.05) percentages of SFA than SEV
      fillets; however, proportions of all monounsaturated fatty acids, as well as
      linoleic and linolenic acids, were greater (P < 0.05) in SEV than NORM fillets.
      These results suggest that an increased growth rate results in increased
      occurrence of higher degrees of white striping in broiler breast fillets, and the
      various degrees of white striping are associated with differences in chemical
      composition of breast fillets.

PMID- 22991558
TI  - Listeria monocytogenes in retailed raw chicken meat in Malaysia.
AB  - This study aimed to determine the prevalence Listeria monocytogenes in raw
      chicken meat samples at hypermarkets and wet markets. Chicken drumsticks,
      breasts, and thighs were randomly selected. The most probable number (MPN) PCR
      method was used to quantify the L. monocytogenes in the samples. Listeria
      monocytogenes was detected in 20% of the samples. Occurrence of L. monocytogenes
      was highest in breast (42.03%) followed by drumstick (11.27%) and thigh (7.14%).
      Samples from hypermarkets showed higher occurrence (25.71%) of L. monocytogenes
      compared with wet markets (14.29%). The density of L. monocytogenes found in
      samples ranged from <3.0 to 16 MPN*g(-1). The presence of L. monocytogenes in raw
      chicken meat is unwanted but unpreventable. Thus, further research on the
      processing method to reduce and eliminate this kind of bacteria in chicken meat
      before consumption is necessary. The presence of L. monocytogenes in chicken
      samples suggests the importance of this pathogen in chicken. Thus, more study is
      needed to find ways to eliminate this pathogen from poultry.

PMID- 22991559
TI  - Effects of dietary probiotic (Pediococcus acidilactici) supplementation on
      performance, nutrient digestibility, egg traits, egg yolk cholesterol, and fatty
      acid profile in laying hens.
AB  - The objective of this study was to determine the effect of dietary probiotic
      Pediococcus acidilactici (PA) strain MA18/5M on performance, egg traits, egg
      cholesterol content, and fatty acid composition in laying hens during a 24-wk
      period. A total of 222 Hy-Line Brown laying hens, 22 wk of age, were divided into
      3 treatment groups. Control group (C) hens were fed a basal diet with no
      probiotic added. In group PA1, the basal diet was supplemented with PA at 100
      mg.kg(-1) of feed for the first 12 wk and 50 mg.kg(-1) feed for the next 12 wk,
      whereas treatment PA2 was supplemented with 100 mg.kg(-1) feed for the whole
      trial period. Dietary treatments did not significantly affect the BW, feed
      intake, and egg production of hens. Pediococcus acidilactici supplementation
      increased egg weight (P < 0.05), eggshell thickness, eggshell relative weight,
      and egg specific gravity, and it improved feed efficiency ratio per kilogram of
      eggs (P < 0.01). Moreover, PA dietary supplementation resulted in a significant
      (P < 0.05) decrease in the number of broken eggs and eggs without the shell,
      leading to a significant (P < 0.01) reduction in the number of downgraded eggs
      (39% for PA1 and 52% for PA2). After 6 mo of probiotic supplementation,
      significant differences were also found in the fatty acid composition and
      cholesterol content of egg yolk. The yolk cholesterol content, regardless of PA
      dose, decreased by more than 10%. The concentrations of total polyunsaturated
      fatty acids, including linoleic acid and linolenic acid, were significantly
      higher in treatment PA2 (6.5% increase) than in C and PA1. In conclusion, dietary
      supplementation of Pediococcus acidilactici MA 18/5M at 100 mg.kg(-1) has
      potential commercial applications for improvements in hen performance and
      eggshell quality during the early laying period.

PMID- 22991560
TI  - Risk factors for Campylobacter infection in Danish broiler chickens.
AB  - Data from the Quality Assurance System in Danish Broiler Production (KIK system)
      were analyzed to identify within farm biosecurity- and management-related risk
      factors for Campylobacter infection in Danish broiler flocks. In the study, data
      from 2,835 flocks originating from 187 farms in the time period of December 2009
      to November 2010 were included. The PCR test results of fecal samples collected
      on socks revealed that 14% of the Danish broiler flocks were positive to
      Campylobacter during the study period. Of the positive flocks, 55% were positive
      during summer time and the positive flocks during summer time were related to
      areas where clustering of infected farms was identified in previous conducted
      studies. The median number of people working in or entering broiler houses was 2
      (from 1 to 7). The median slaughter age of Danish broiler flocks was 35 d (from
      31-61 d). A multivariable logistic regression model with a random effect of farm
      was performed. The analysis revealed that flocks had a higher risk of acquiring
      positive infection status during summer time: odds ratio = 12.59 (95% CI: 6.79
      23.36) and when more than one person entered the broiler house: odds ratio = 2.03
      (95% CI: 1.19-3.84). Furthermore, there was a higher risk of a positive infection
      status if the test result of the farm for the previous flock was positive: odds
      ratio = 1.80 (95% CI: 1.22-2.63), if the broiler houses were built before and
      during 1990: odds ratio = 1.60 (95% CI: 1.17-2.18), and if the average slaughter
      age of the birds was more than 35 d: odds ratio = 1.33 (95% CI: 1.02-1.76).

PMID- 22991561
TI  - Fuzzy modeling to predict chicken egg hatchability in commercial hatchery.
AB  - Experimental studies have shown that hatching rate depends, among other factors,
      on the main physical characteristics of the eggs. The physical parameters used in
      our work were egg weight, eggshell thickness, egg sphericity, and yolk per
      albumen ratio. The relationships of these parameters in the incubation process
      were modeled by Fuzzy logic. The rules of the Fuzzy modeling were based on the
      analysis of the physical characteristics of the hatching eggs and the respective
      hatching rate using a commercial hatchery by applying a trapezoidal membership
      function into the modeling process. The implementations were performed in
      software. Aiming to compare the Fuzzy with a statistical modeling, the same data
      obtained in the commercial hatchery were analyzed using multiple linear
      regression. The estimated parameters of multiple linear regressions were based on
      a backward selection procedure. The results showed that the determination
      coefficient and the mean square error were higher using the Fuzzy method when
      compared with the statistical modeling. Furthermore, the predicted hatchability
      rates by Fuzzy Logic agreed with hatching rates obtained in the commercial
      hatchery.

PMID- 22991562
TI  - Global variation and uniformity of eggshell thickness for chicken eggs.
AB  - Damaged eggshells result in losses of eggs. Numerous efforts have been carried
      out to improve eggshell quality, which may lead to increased eggshell thickness.
      The conventional way of enhancing eggshell strength with thicker eggshell on
      average may be replaced by a new strategy to improve eggshell uniformity without
      increasing eggshell thickness. To achieve this, it is necessary to investigate
      global variation of eggshell thickness. In this study, we used 100 fresh eggs
      from 52-wk-old layers of a commercial brown-egg variety. To determine the global
      variation of eggshell thickness, 42 points for each egg along both longitudinal
      and latitudinal axes were selected to measure thickness using an eggshell
      thickness gauge. The eggshell thickness from blunt to sharp end varied
      significantly (P < 0.05). The area surrounding the blunt end was the thinnest
      (0.341 +/- 0.025 mm), whereas the area surrounding the sharp end was the thickest
      (0.367 +/- 0.023 mm). It was found that the thickness of the sharp end was the
      closest to the average thickness of the whole eggshell and could be considered as
      a valid measurement of eggshell thickness. A new parameter, eggshell thickness
      uniformity, was defined as the reciprocal of the coefficient of variation (1/CV)
      of eggshell thickness from 42 points of each egg and can be used to evaluate the
      eggshell quality. Eggshell thickness uniformity was positively correlated with
      breaking strength (r = 0.341; P < 0.01), suggesting that the parameter may be
      used as a potential selection criterion in breeding program to improve eggshell
      quality without increasing eggshell thickness.

PMID- 22991564
TI  - Environmental changes to promote physical activity and healthy dietary behavior.

PMID- 22991566
TI  - Gene expression profiling in dermatitis herpetiformis skin lesions.
AB  - Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated
      with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis
      of skin lesions at molecular level, we analysed the gene expression profiles in
      skin biopsies from 6 CD patients with DH and 6 healthy controls using Affymetrix
      HG-U133A 2.0 arrays. 486 genes were differentially expressed in DH skin compared
      to normal skin: 225 were upregulated and 261 were downregulated. Consistently
      with the autoimmune origin of DH, functional classification of the differentially
      expressed genes (DEGs) indicates a B- and T-cell immune response (LAG3, TRAF5,
      DPP4, and NT5E). In addition, gene modulation provides evidence for a local
      inflammatory response (IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with
      concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cell activation, and
      neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of
      matrix proteases (MMP9, ADAM9, and ADAM19) and proteolytic enzymes (CTSG, ELA2,
      CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting and blister
      formation. Finally, we observed modulation of genes involved in cell growth
      inhibition (CGREF1, PA2G4, and PPP2R1B), increased apoptosis (FAS, TNFSF10, and
      BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, and
      LAMA5). In conclusion, our results identify genes that are involved in the
      pathogenesis of DH skin lesions.

PMID- 22991567
TI  - Human antibodies can cross guinea pig placenta and bind its neonatal Fc Receptor:
      implications for studying immune prophylaxis and therapy during pregnancy.
AB  - Despite increased use of monoclonal and polyclonal antibody therapies, including
      during pregnancy, there is little data on appropriate animal models that could
      humanely be used to understand determinants of protection and to evaluate safety
      of these biologics in the mother and the developing fetus. Here, we demonstrate
      that pregnant guinea pigs can transport human IgG transplacentally at the end of
      pregnancy. We also observe that human IgG binds to an engineered soluble variant
      of the guinea pig neonatal Fc receptor in vitro in a manner similar to that
      demonstrated for the human variant, suggesting that this transplacental transport
      mirrors the receptor-based mechanism seen in humans. Using an intravenous
      antihepatitis B-specific immune globulin preparation as an example, we show that
      this transport results in neutralizing activity in the mother and the newborn
      that would potentially be prophylactic against hepatitis B viral infection. These
      preliminary data lay the groundwork for introducing pregnant guinea pigs as an
      appropriate model for the evaluation of antibody therapies and advancing the
      health of women and neonates.

PMID- 22991568
TI  - Transfer of maternal immunity to newborns of diabetic mothers.
AB  - This study was carried out with hyperglycemic pregnant women to investigate the
      transfer of antibody classes to newborns across the placenta or by colostrum and
      the functional activity of phagocytes in maternal blood, cord blood, and
      colostrum from diabetes mothers. Samples from maternal blood, cord blood, and
      colostrum were collected from 20 normoglycemic and 20 hyperglycemic pregnant
      women. We determined antibodies levels, superoxide release, phagocytosis and
      bactericidal activity of phagocytes. We demonstrated that IgG levels in cord
      blood were higher in the hyperglycemic group. IgA and IgM levels were higher in
      maternal than in cord blood samples. Plasma antibody levels were lower in hyper-
      than in normoglycemic women. The colostrum of diabetic mothers had lower IgA and
      IgG levels. Colostrum and maternal blood phagocytes when exposed to EPEC
      increased the superoxide release. Cord blood phagocytes of hyperglycemic group,
      independently of bacteria, had higher superoxide release. Colostrum and blood
      phagocytes from diabetic group exhibited some phagocytic and microbicidal
      activity in response to EPEC. Mononuclear phagocytes from cord blood had the
      lowest phagocytosis, and bactericidal activity for EPEC, regardless of glycemic
      status. These data showed that hyperglycemia altered IgG transfer across the
      placenta and decreases immunoglobulin levels in maternal blood and colostrum.

PMID- 22991569
TI  - Effects of yoga interventions on fatigue: a meta-analysis.
AB  - Background. Researchers aimed at systematically reviewing and meta-analyzing the
      effectiveness of yoga interventions for fatigue. Methods. PubMed/Medline was
      searched until January 2012 for controlled clinical studies. Two reviewers
      independently extracted the data. The methodological quality of the studies was
      assessed. A meta-analysis was performed. Results. Nineteen clinical studies
      (total n = 948) were included in this review. Investigated yoga styles included
      Hatha, Iyengar, Asanas, Patanjali, Sahaja, and Tibetan yoga. Participants were
      suffering from cancer, multiple sclerosis, dialysis, chronic pancreatitis,
      fibromyalgia, asthma, or were healthy. Yoga had a small positive effect on
      fatigue (SMD = 0.27, 59% CI = 0.23-0.31). Seven studies received 4 points on the
      Jadad score. There were baseline differences in at least 5 studies. Conclusion.
      Overall, the effects of yoga interventions on fatigue were only small,
      particularly in cancer patients. Although yoga is generally a safe therapeutic
      intervention and effective to attenuate other health-related symptoms, this meta
      analysis was not able to define the powerful effect of yoga on patients suffering
      from fatigue. Treatment effects of yoga could be improved in well-designed future
      studies. According to the GRADE recommendations assessing the overall quality of
      evidence, there is a moderate effect of the confidence placed in the estimates of
      the effects discussed here.

PMID- 22991570
TI  - Analgesic and Anti-Inflammatory Activities of Methanol Extract of Cissus repens
      in Mice.
AB  - The aim of this study was to investigate possible analgesic and anti-inflammatory
      mechanisms of the CR(MeOH). Analgesic effect was evaluated in two models
      including acetic acid-induced writhing response and formalin-induced paw licking.
      The anti-inflammatory effect was evaluated by lambda-carrageenan-induced mouse
      paw edema and histopathologic analyses. The results showed that CR(MeOH) (500
      mg/kg) decreased writhing response in the acetic acid assay and licking time in
      the formalin test. CR(MeOH) (100 and 500 mg/kg) significantly decreased edema paw
      volume at 4th to 5th hours after lambda-carrageenan had been injected.
      Histopathologically, CR(MeOH) abated the level of tissue destruction and swelling
      of the edema paws. These results were indicated that anti-inflammatory mechanism
      of CR(MeOH) may be due to declined levels of NO and MDA in the edema paw through
      increasing the activities of SOD, GPx, and GRd in the liver. Additionally,
      CR(MeOH) also decreased IL-1beta, IL-6, NFkappaB, TNF-alpha, COX-2, and iNOS
      levels. The contents of two active ingredients, ursolic acid and lupeol, were
      quantitatively determined. This paper demonstrated possible mechanisms for the
      analgesic and anti-inflammatory effects of CR(MeOH) and provided evidence for the
      classical treatment of Cissus repens in inflammatory diseases.

PMID- 22991571
TI  - Ferulsinaic Acid Modulates SOD, GSH, and Antioxidant Enzymes in Diabetic Kidney.
AB  - The efficacy of Ferulsinaic acid (FA) to modulate the antioxidant enzymes and to
      reduce oxidative stress induced-diabetic nephropathy (DN) was studied. Rats were
      fed diets enriched with sucrose (50%, wt/wt), lard (30%, wt/wt), and cholesterol
      (2.5%, wt/wt) for 8 weeks to induce insulin resistance. After a DN model was
      induced by streptozotocin; 5, 50 and 500 mg/kg of FA were administrated by oral
      intragastric intubation for 12 weeks. In FA-treated diabetic rats, glucose,
      kidney/body weight ratio, creatinine, BUN, albuminurea, and creatinine clearance
      were significantly decreased compared with non treated diabetic rats. Diabetic
      rats showed decreased activities of SOD and GSH; increased concentrations of
      malondialdehyde and IL-6 in the serum and kidney, and increased levels of 8
      hydroxy-2'-deoxyguanosine in urine and renal cortex. FA-treatment restored the
      altered parameters in a dose-dependent manner. The ultra morphologic
      abnormalities in the kidney of diabetic rats were markedly ameliorated by FA
      treatment. Furthermore, FA acid was found to attenuate chronic inflammation
      induced by both Carrageenan and dextran in rats. We conclude that FA confers
      protection against injuries in the kidneys of diabetic rats by increasing
      activities of antioxidant enzymes and inhibiting accumulation of oxidized DNA in
      the kidney, suggesting a potential drug for the prevention and therapy of DN.

PMID- 22991565
TI  - Endocrine-disrupting chemicals: associated disorders and mechanisms of action.
AB  - The incidence and/or prevalence of health problems associated with endocrine
      disruption have increased. Many chemicals have endocrine-disrupting properties,
      including bisphenol A, some organochlorines, polybrominated flame retardants,
      perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic
      aromatic hydrocarbons, alkylphenols, solvents, and some household products
      including some cleaning products, air fresheners, hair dyes, cosmetics, and
      sunscreens. Even some metals were shown to have endocrine-disrupting properties.
      Many observations suggesting that endocrine disruptors do contribute to cancer,
      diabetes, obesity, the metabolic syndrome, and infertility are listed in this
      paper. An overview is presented of mechanisms contributing to endocrine
      disruption. Endocrine disruptors can act through classical nuclear receptors, but
      also through estrogen-related receptors, membrane-bound estrogen-receptors, and
      interaction with targets in the cytosol resulting in activation of the
      Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in
      metabolism of endogenous hormones, cross-talk between genomic and nongenomic
      pathways, cross talk with estrogen receptors after binding on other receptors,
      interference with feedback regulation and neuroendocrine cells, changes in DNA
      methylation or histone modifications, and genomic instability by interference
      with the spindle figure can play a role. Also it was found that effects of
      receptor activation can differ in function of the ligand.

PMID- 22991572
TI  - Ameliorative Effects of Scopoletin from Crossostephium chinensis against
      Inflammation Pain and Its Mechanisms in Mice.
AB  - Scopoletin exists in nature as an anti-oxidant, hepatoprotective, and anti
      inflammatory activities reagent. In this study, we have investigated the
      analgesic effects of the scopoletin using the models of acetic acid-induced
      writhing response and the formalin test, the anti-inflammatory effects of
      scopoletin using model of lambda-carrageenan (Carr)-induced paw edema. The
      treatment of ICR mice with scopoletin inhibited the numbers of writhing response
      and the formalin-induced pain in the late phase. This study demonstrated that the
      administration of scopoletin resulted in the reduction of Carr-induced mice
      edema, and it increased the activities of superoxide dismutase (SOD), catalase
      (CAT), and glutathione peroxidase (GPx) after Carr injection. We also
      demonstrated scopoletin significantly attenuated the malondialdehyde (MDA) level
      in the edema paw after Carr injection. Scopoletin decreased the NO, tumor
      necrosis factor (TNF-alpha) and prostaglandin E2 (PGE(2)) levels on serum after
      Carr injection. Scopoletin decreased Carr-induced inducible NO synthase (iNOS)
      and cyclooxygenase-2 (COX-2) expressions in the edema paw. These anti
      inflammatory mechanisms of scopoletin might be related to the decrease in the
      level of MDA via increasing the activities of SOD, CAT, and GPx in the edema paw.
      Also, scopoletin could affect the production of NO, TNF-alpha, and PGE(2), and
      therefore affect the anti-inflammatory effects.

PMID- 22991574
TI  - Labisia pumila Prevents Complications of Osteoporosis by Increasing Bone Strength
      in a Rat Model of Postmenopausal Osteoporosis.
AB  - Estrogen replacement therapy (ERT) is the main treatment postmenopausal
      osteoporosis. However, ERT causes serious side effects, such as cancers and
      thromboembolic problems. Labisia pumila var. alata (LPva) is a herb with
      potential as an alternative to ERT to prevent complications of osteoporosis,
      especially fragility fractures. This study was conducted to determine the effects
      of LPva on the biomechanical strength of femora exposed to osteoporosis due to
      estrogen deficiency, using the postmenopausal rat model. Thirty-two female rats
      were randomly divided into four groups: Sham-operated (Sham), ovariectomized
      control (OVXC), ovariectomized with Labisia pumila var. alata (LP), and
      ovariectomized with ERT (Premarin) (ERT). The LPva and ERT were administered via
      oral gavage daily at doses of 17.5 mg/kg and 64.5 MUg/kg, respectively. Following
      two months of treatment, the rats were euthanized, and their right femora were
      prepared for bone biomechanical testing. The results showed that ovariectomy
      compromised the femoral strength, while LPva supplementation to the
      ovariectomized rats improved the femoral strength. Therefore, LPva may be as
      effective as ERT in preventing fractures due to estrogen-deficient osteoporosis.

PMID- 22991575
TI  - Prediction of breeding values for dairy cattle using artificial neural networks
      and neuro-fuzzy systems.
AB  - Developing machine learning and soft computing techniques has provided many
      opportunities for researchers to establish new analytical methods in different
      areas of science. The objective of this study is to investigate the potential of
      two types of intelligent learning methods, artificial neural networks and neuro
      fuzzy systems, in order to estimate breeding values (EBV) of Iranian dairy
      cattle. Initially, the breeding values of lactating Holstein cows for milk and
      fat yield were estimated using conventional best linear unbiased prediction
      (BLUP) with an animal model. Once that was established, a multilayer perceptron
      was used to build ANN to predict breeding values from the performance data of
      selection candidates. Subsequently, fuzzy logic was used to form an NFS, a hybrid
      intelligent system that was implemented via a local linear model tree algorithm.
      For milk yield the correlations between EBV and EBV predicted by the ANN and NFS
      were 0.92 and 0.93, respectively. Corresponding correlations for fat yield were
      0.93 and 0.93, respectively. Correlations between multitrait predictions of EBVs
      for milk and fat yield when predicted simultaneously by ANN were 0.93 and 0.93,
      respectively, whereas corresponding correlations with reference EBV for
      multitrait NFS were 0.94 and 0.95, respectively, for milk and fat production.

PMID- 22991576
TI  - Computational analysis of cardiovascular hemodynamics.

PMID- 22991573
TI  - Herbal products: benefits, limits, and applications in chronic liver disease.
AB  - Complementary and alternative medicine soughts and encompasses a wide range of
      approaches; its use begun in ancient China at the time of Xia dynasty and in
      India during the Vedic period, but thanks to its long-lasting curative effect,
      easy availability, natural way of healing, and poor side-effects it is gaining
      importance throughout the world in clinical practice. We conducted a review
      describing the effects and the limits of using herbal products in chronic liver
      disease, focusing our attention on those most known, such as quercetin or
      curcumin. We tried to describe their pharmacokinetics, biological properties, and
      their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral
      hepatitis (considering that oxidative stress is the common pathway of chronic
      liver diseases of different etiology). The main limit of applicability of CAM
      comes from the lacking of randomized, placebo-controlled clinical trials giving a
      real proof of efficacy of those products, so that anecdotal success and personal
      experience are frequently the driving force for acceptance of CAM in the
      population.

PMID- 22991577
TI  - Methodological advances in brain connectivity.

PMID- 22991578
TI  - The use of fractal dimension analysis in estimation of blood vessels shape in
      transplantable mammary adenocarcinoma in Wistar rats after photodynamic therapy
      combined with cysteine protease inhibitors.
AB  - Fractal dimension analysis (FDA) is modern mathematical method widely used to
      describing of complex and chaotic shapes when classic methods fail. The main aim
      of this study was evaluating the influence of photodynamic therapy (PDT) with
      cystein proteases inhibitors (CPI) on the number and morphology of blood vessels
      inside tumor and on increase of effectiveness of combined therapy in contrast to
      PDT and CPI used separately. Animals were divided into four groups: control,
      treated using only PDT, treated using only CPI and treated using combined
      therapy, PDT and CPI. Results showed that time of animal survival and depth of
      necrosis inside tumor were significantly higher in CPI+PDT group in contrast to
      other groups. The higher value of fractal dimension (FD) was observed in control
      group, while the lowest value was found in the group which was treated by cystein
      protease inhibitors. The differences between FD were observed in CPI group and
      PDT+CPI group in comparison to control group. Our results revealed that fractal
      dimension analysis is a very useful tool in estimating differences between
      irregular shapes like blood vessels in PDT treated tumors. Thus, the
      implementation of FDA algorithms could be useful method in evaluating the
      efficacy of PDT.

PMID- 22991579
TI  - Sight restoration.
AB  - Cases of sight onset after extended periods of congenital blindness provide
      windows into visual development and brain plasticity. Such cases are extremely
      rare in the developed world. Here, we make the argument that in meeting a public
      health challenge in the developing world, that of providing treatment to curably
      blind children, we have the opportunity to have a beneficial impact on science
      and society simultaneously. A recent initiative, Project Prakash, is motivated by
      these twin goals. We briefly describe this effort, some of its early results, and
      also the caveats that need to be kept in mind when interpreting the findings.

PMID- 22991580
TI  - New therapeutic approaches for malignant glioma: in search of the Rosetta stone.
AB  - Malignant gliomas are heterogeneous, diffuse and highly infiltrating by nature.
      Despite wide surgical resection and improvements in radio- and chemotherapies,
      the prognosis of patients with glioblastoma multiforme remains extremely poor,
      with a median survival time of only 14.5 months from diagnosis to death.
      Particular challenges for glioblastoma multiforme therapy are posed by
      limitations in the extent of feasible surgical resections, distinct tumor
      heterogeneity, difficulties in drug delivery across the blood-brain barrier and
      low drug distribution within the tumor. Therefore, new paradigms permitting tumor
      specific targeting and extensive intratumoral distribution must be developed to
      allow an efficient therapeutic delivery. This review highlights the latest
      advances in the treatment of glioblastoma multiforme and the recent developments
      that have resulted from the interchange between preclinical and clinical efforts.
      We also summarize and discuss novel therapies for malignant glioma, focusing on
      advances in the following main topics of glioblastoma multiforme therapy:
      immunotherapy, gene therapy, stem cell-based therapies and nanotechnology. We
      discuss strategies and outcomes of emerging therapeutic approaches in these
      fields, and the main challenges associated with the integration of discoveries
      that occur in the laboratory into clinical practice.

PMID- 22991581
TI  - Development of the germinal ridge and ovary in the African elephant (Loxodonta
      africana).
AB  - The follicular reserve and its ontogeny in the elephant are of interest because
      elephants have the longest reproductive life of all land-based mammals. They also
      have the longest recorded pregnancy, which allows a protracted view of the series
      of significant events involved in the development of the embryonic and fetal
      gonads. The large elephant population of Zimbabwe provided the opportunity to
      collect conceptuses from elephants culled for management reasons and hunted
      professionally. Five embryos aged 76-96 days and the ovaries of four fetuses aged
      4.8-11.2 months were fixed in 4% buffered formalin and studied by conventional
      histological sectioning and a stereological protocol to calculate the follicle
      reserve of each fetus. These observations enabled the conclusion that the
      migration of primordial germ cells into the indifferent gonad terminates at
      around 76 days of gestation while entry of oogonia into meiosis along with first
      follicle formation starts at around 5 months. Peak numbers of follicles are
      present by mid-gestation towards the end of the 6-month mitotic-meiotic
      transition period. It appears that the cortex of the elephant fetal ovary at mid
      gestation (11 months) has already reached a developmental stage exhibited by the
      ovaries of many other mammals at full term.

PMID- 22991582
TI  - Ocean viruses and their effects on microbial communities and biogeochemical
      cycles.
AB  - Viruses are the most abundant life forms on Earth, with an estimated 10(31) total
      viruses globally. The majority of these viruses infect microbes, whether
      bacteria, archaea or microeukaryotes. Given the importance of microbes in driving
      global biogeochemical cycles, it would seem, based on numerical abundances alone,
      that viruses also play an important role in the global cycling of carbon and
      nutrients. However, the importance of viruses in controlling host populations and
      ecosystem functions, such as the regeneration, storage and export of carbon and
      other nutrients, remains unresolved. Here, we report on advances in the study of
      ecological effects of viruses of microbes. In doing so, we focus on an area of
      increasing importance: the role that ocean viruses play in shaping microbial
      population sizes as well as in regenerating carbon and other nutrients.

PMID- 22991583
TI  - Epigenetic synthesis: a need for a new paradigm for evolution in a contaminated
      world.
AB  - Epigenetics is a perspective, not a set of techniques. Molecular biology and
      genetics are the dominant disciplines in biology today, but practitioners of
      these fields have only recently 'rediscovered' the importance of the environment.
      This has led to increasing research into molecular epigenetics and the interface
      between the environment and gene regulation. Beyond the study of epigenetic
      mechanisms at the level of the gene, more investigation of epigenetic outcomes at
      the level of both the individual organism and the evolution of the population is
      needed.

PMID- 22991585
TI  - A special issue.

PMID- 22991587
TI  - Evaluation of Relationship between Lichen Planus and HCV Antibody.
AB  - BACKGROUND AND AIMS: Lichen planus is a relatively common chronic mucocutaneaous
      disease with an unknown cause, and is considered a manifestation of cell-mediated
      immune response. Hepatitis C virus (HCV) and its subgroups have been associated
      with lichen planus in different geographic locations. The present study was
      undertaken to evaluate the prevalence of HCV antibody in patients with lichen
      planus in northwest Iran. MATERIALS AND METHODS: This descriptive analytical
      study included 30 patients with cutaneous lichen planus, 30 pa-tients with oral
      lichen planus, and 30 healthy individuals as controls. Anti-HCV test was run for
      all the subjects. Descriptive statistics as well as chi-square test, to compare
      means in the three study groups, were applied to the data using SPSS 14.0
      computer software. RESULTS: Age and sex differences between the groups were not
      significant. No statistically significant differences were ob-served in anti-HCV
      test results between the groups (P = 0.50). CONCLUSION: No statistically
      significant relationships were observed between lichen planus and HCV antibody in
      the studied samples.

PMID- 22991586
TI  - Oral lichen planus: clinical features, etiology, treatment and management; a
      review of literature.
AB  - Lichen planus is a chronic inflammatory mucocutaneous disease. Mucosal lesions
      are classified into six clinical forms and there is malignant potential for two
      forms of OLP; therefore, follow-up should be considered. There are many un
      established etiological factors for OLP and some different treatment modalities
      are based on etiology. The aims of current OLP therapy are to eliminate mucosal
      erythema and ulceration, alleviate symptoms and reduce the risk of oral cancer.
      We have used review papers, case reports, cohort studies, and case-and-control
      studies published from 1985 to 2010 to prepare this review of literature.

PMID- 22991584
TI  - Nutraceutical interventions for promoting healthy aging in invertebrate models.
AB  - Aging is a complex and inevitable biological process that is associated with
      numerous chronically debilitating health effects. Development of effective
      interventions for promoting healthy aging is an active but challenging area of
      research. Mechanistic studies in various model organisms, noticeably two
      invertebrates, Caenorhabditis elegans and Drosophila melanogaster, have
      identified many genes and pathways as well as dietary interventions that modulate
      lifespan and healthspan. These studies have shed light on some of the mechanisms
      involved in aging processes and provide valuable guidance for developing
      efficacious aging interventions. Nutraceuticals made from various plants contain
      a significant amount of phytochemicals with diverse biological activities.
      Phytochemicals can modulate many signaling pathways that exert numerous health
      benefits, such as reducing cancer incidence and inflammation, and promoting
      healthy aging. In this paper, we outline the current progress in aging
      intervention studies using nutraceuticals from an evolutionary perspective in
      invertebrate models.

PMID- 22991588
TI  - Prevalence of Candida species in erosive oral lichen planus.
AB  - BACKGROUND AND AIMS: The clinical management of oral lichen planus poses
      considerable difficulties to the clinician. In recent years, researchers have
      focused on the presence of pathogenic microorganisms such as Candida albicans in
      the patients with refractory lichen planus. The aim of the present study was to
      investigate the prevalence of candida species in the erosive oral lichen planus
      lesions. MATERIALS AND METHODS: Twenty-one patients with erosive oral lichen
      planus and twenty-one healthy individuals aged 18-60 were randomly selected;
      samples were taken from the tongue, saliva and buccal mucosa with swab friction.
      Theses samples were sent to the laboratory for determining the presence of
      candida species in cultures and direct examination method. RESULTS: No
      significant difference was found between healthy individuals and patients with
      erosive lichen planus regard-ing presence of candida species. The type of candida
      in the evaluated samples was Candida albicans in both healthy and patient groups.
      CONCLUSION: According to the results, candida was not confirmed as an etiologic
      factor for erosive lichen planus lesions.

PMID- 22991589
TI  - Relationship between Lichen Planus and Helicobacter pylori Infection.
AB  - BACKGROUND AND AIMS: Lichen planus (LP) is a relatively common, chronic dermato
      mucosal disease that often affects the oral mucosa. Among bacterial infections
      affecting LP, Helicobacter pylori has recently been proposed as an important
      etiologic factor. The present study was designed to evaluate the association of
      LP and H. pylori infection. MATERIALS AND METHODS: This study included 30
      patients with skin LP, 30 patients with oral LP and 30 healthy individuals
      without LP as control group. Patients and control group were selected from those
      referred to a dental and a dermatology clinic. Urea breathing test (UBT) was
      performed for all subjects. Descriptive statistic (frequency and percentage) were
      applied and chi-square test was employed to compare mean differences, using SPSS
      13.0 computer software. RESULTS: UBT test were positive in 24 patients (80%) in
      oral LP group, 22 patients (73.3%) in skin LP group, and 20 individuals (66.7%)
      in the control group. No significant differences were found in the positive test
      results between the three groups (P = 0.50). CONCLUSION: In this study, no
      significant association was found between LP and H. Pylori infection.

PMID- 22991590
TI  - Comparison of the effect of combination of triamcinolone acetonide and vitamin a
      mouthwash with triamcinolone mouthwash alone on oral lichen planus.
AB  - BACKGROUND AND AIMS: Lichen planus is a relatively common mucocutaneous disease,
      with an unknown etiology. There is no complete cure for oral lichen planus (OLP),
      but some drugs, including corticosteroids, retinoids, cyclosporine and
      antibiotics are commonly used for treatment of OLP. The aim of the present study
      was to compare the effect of combi-nation of triamcinolone and vitamin A
      mouthwash with triamcinolone mouthwash alone on OLP. MATERIALS AND METHODS:
      Twenty OLP patients were randomly divided into two groups of 10. The experimental
      group was treated with combination of triamcinolone and vitamin A mouthwash and
      the control group was treated with triamcinolone-containing mouthwash alone. The
      patients were examined once every two weeks and the lesion size, pain and burning
      sensation were recorded based on visual analogue scale during a two-month period.
      Data were analyzed by Mann-Whitney U test using SPSS software. RESULTS: The use
      of combination of triamcinolone-vitamin A mouthwash was effective in decreasing
      the pain and burning sensation of OLP (P = 0.012). Decrease in pain and burning
      sensation were similar in both groups (P = 0.73). The use of combination of
      triamcinolone-vitamin A mouthwash led to a decrease in the size of keratotic,
      atrophic and erosive OLP lesions (P = 0). Decrease in the size of the lesions was
      significantly greater in the study group compared to the control group (P =
      0.029). CONCLUSION: The use of combination of triamcinolone-vitamin A mouthwash
      is effective in decreasing the size of keratotic, atrophic or erosive lesions.

PMID- 22991591
TI  - Comparison of the Effect of Mouthwashes with and without Zinc and Fluocinolone on
      the Healing Process of Erosive Oral Lichen Planus.
AB  - BACKGROUND AND AIMS: Lichen planus is a chronic inflammatory disorder with
      unspecified etiology, appearing as a result of stress, genetic predisposition and
      immunologic factors. Erosive type of the disease is more important because of its
      clinical symptoms of pain, irritation and malignancy risk. Despite various
      medications used, a definite cure for lichen planus is un-known. Regarding the
      effect of zinc on healing of ulcers, the aim of this study was to compare the
      effect of a mouthwash with and without zinc and fluocinolone on healing of
      erosive oral lichen planus. MATERIALS AND METHODS: Twenty randomly-selected
      patients with erosive oral lichen planus were divided into two groups of 10. One
      group received zinc mouthwash with fluocinolone ointment and the other group
      received placebo with ointment. The largest dimension of the ulcers was measured
      by digital calipers and the intensity of pain was determined by visual ana-logue
      scale. Data was analyzed with Mann-Whitney U test. RESULTS: Pain, irritation and
      lesion surface area decreased in both groups. Decrease in pain severity was
      identical in both groups (P = 0.11). However, decrease in surface area with zinc
      mouthwash plus fluocinolone was more than that with only fluocinolone (P =
      0.037). CONCLUSION: 0.2% zinc mouthwash plus fluocinolone and only fluocinolone
      were both effective in decreasing pain, irrita-tion, and surface area of OLP.
      However, decrease in surface area with zinc mouthwash plus fluocinolone was more
      than that with fluocinolone alone.

PMID- 22991592
TI  - Efficacy of Elaeagnus angustifolia Topical Gel in the Treatment of Symptomatic
      Oral Lichen Planus.
AB  - BACKGROUND AND AIMS: The purpose of this study was to determine efficacy of 19%
      Elaeagnus angustifolia (EA) topical gel in the treatment of symptomatic oral
      lichen planus. MATERIALS AND METHODS: Patients with symptomatic oral lichen
      planus referring to the Department of Oral Medicine, Fac-ulty of Dentistry at
      Shahid Beheshti University of Medical Sciences were asked to participate in the
      study. Twenty-eight pa-tients who were histopathologically diagnosed with lichen
      planus were divided into two groups (15 in the case and 13 in the control
      groups). The subjects were randomly assigned to either topical gel of EA or
      placebo in a double-blind manner. They were then instructed to apply the
      medication on dried lesions three times daily. Pain and size of the lesions were
      evaluated after 2 weeks. Data were analyzed by SPSS 12.0 software, using t-test,
      paired t-test, Fisher's exact test and chi-square test. RESULTS: Twenty-eight
      patients (m/f: 7/21) with symptomatic oral lichen planus participated in the
      study. Fifteen patients (m/f: 4/11) received E A gel and 13 patients (m/f: 3/10)
      received placebo. There was a 75% decrease in pain (33.3% in the case and 7.7% in
      the control groups), and a decrease of 50% in size (33.3% in the case group) and
      75% only in 7.6% of the case group. CONCLUSION: The results suggest that 19% EA
      gel is efficient in the treatment of symptomatic oral lichen planus, with anti
      inflammatory and analgesic effects, as well.

PMID- 22991593
TI  - Treatment of desquamative gingivitis with free gingival graft: a case report.
AB  - Recalcitrant gingival erythematous lichen planus lesions comprise a considerable
      therapeutic problem. This case of chronic desquamative gingivitis in a 25-year
      old woman with erosive oral lichen planus was treated with topical and systemic
      corti-costeroid administration, followed by placement of a free gingival graft on
      right upper quadrant. Although recurrence of the lesions was observed following
      both treatment modalities, free gingival graft despite being an aggressive
      therapy, proved more effective and with fewer side effects compared with topical
      or systemic steroid therapy, and seems to be a promising treatment modality with
      the benefit of more stable results, among others.

PMID- 22991594
TI  - Correlation between Burning Mouth Syndrome and Anxiety in the Elderly Inmates of
      Sanitaria in Tehran.
AB  - BACKGROUND AND AIMS: Burning mouth syndrome (BMS) is a chronic pain disorder
      characterized by a chief complaint of oral burning/pain with no clinically
      observable oral mucosal lesions. The prevalence of BMS has been reported to be
      2.5-5.1% in the general population and several psychological disorders have been
      reported as associated or predisposing factors for BMS. The aim of this study was
      to determine the correlation between BMS and anxiety in the elderly residents of
      sani-taria in Tehran, Iran. MATERIALS AND METHODS: In a cross-sectional
      analytical study, 50 patients with BMS were included along with 50 healthy
      individuals as controls. Inclusion criteria were: age over 60 years, burning
      sensation in the mouth, normal oral mu-cosa, absence of diabetes, satisfactory
      prosthesis, absence of iron deficiency and other nutrients, and no heavy smoking
      habits. Similar inclusion criteria were considered for the control group without
      any oral complaints. Burning/pain severity was assessed by a 100-mm visual analog
      scale and the severity of anxiety (state, trait, and total) was determined by
      Cattell's Anxiety Scale. Data was analyzed by t-test and Pearson's correlation
      coefficient. RESULTS: Individuals with BMS assessed their burning/pain severity
      to be 27.4 mm (95% CI=25.2 - 29.6 mm). Standard-ized total anxiety scale in
      individuals with and without BMS (+/-SE for mean) was 5.9+/-0.2 and 4.6+/-0.3
      with significant dif-ferences (p=0.001). Similar significant differences were
      observed in state and trait anxiety between the two groups. CONCLUSION: It seems
      that both state and trait anxiety are associated with burning mouth syndrome.

PMID- 22991595
TI  - Prevalence and Pattern of Pain Presentation among Patients Attending a Tertiary
      Dental Center in a Southern Region of Nigeria.
AB  - BACKGROUND AND AIMS: Orofacial pain is one of the most common reasons for
      attendance at the dental clinic. The prevalence and the sources of orofacial pain
      vary from place to place and patients' response to pain also differs. The aim of
      this study was to determine the prevalence and pattern of orofacial pain as well
      as the factors influencing patients' response to orofacial pain among patients
      presenting for dental treatment in our center. MATERIALS AND METHODS: Consecutive
      patients presenting with orofacial pain at the Dental Center, University of Port
      Harcourt Teaching Hospital during the one-year period of the study were recruited
      into the study. Patients' demographic data were collected and recorded in special
      forms. Patients were later examined to confirm the specific cause of pain. This
      was also recorded. Data generated were analyzed using SPSS for Windows. RESULTS:
      Four hundred and forty-eight patients out of the 2,426 patients seen during the
      study period had orofacial pain, yielding a prevalence rate of 18.5%. There were
      255 females and 193 males with most patients in the 17-27-year age group (49.1%).
      Lower jaw was commonly affected. Most patients presented after a period of at
      least one month, with severe and spontaneous pain. Most patients had drug therapy
      before presentation. Caries was the most common source of orofacial pain.
      CONCLUSION: Orofacial pain was not uncommon in our center and it accounted for
      about 20% of patients' attendance in the center. Dental caries and periodontal
      diseases were the most common sources of orofacial pain while temporomandibu-lar
      joint pain and atypical facial pain were not common in our center. Young adults
      and females were most commonly affected.

PMID- 22991596
TI  - The position of lingula as an index for inferior alveolar nerve block injection
      in 7-11-year-old children.
AB  - BACKGROUND AND AIMS: Inferior alveolar nerve block injection is one of the common
      intra oral anesthetic techniques, with a failure rate of 15-20%. The aim of this
      study was to evaluate the position of the lingula as an index for this injection.
      MATERIALS AND METHODS: Thirty eight panoramic radiographs of 7-11 year old
      patients were analyzed and the distance between the lingula index and occlusal
      plane was measured. Then, lower alveolar nerve block injection was performed on
      88 children. Finally, a visual analogue scale was used to measure the rate of
      pain in the patients. RESULTS: This distance increased with age and in children
      younger than nine years is -0.45 mm on the right side and -0.95 mm on the left
      side. This distance in children older than 9 years is -0.23 mm on the right side
      and 0.47 mm on the left side. The success rates of inferior alveolar nerve block
      injection based on lingual index were 49% on the right side and 53.8% on the left
      side. CONCLUSION: As the lingual index has various positions and its distance
      from the occlusal plane increases with age, it is not an appropriate landmark for
      inferior alveolar nerve block injection.

PMID- 22991597
TI  - Dental treatment needs of permanent first molars in mashhad schoolchildren.
AB  - BACKGROUND AND AIMS: In spite of their enormous importance, permanent first
      molars might be affected by caries in children in developing countries. The aim
      of this study was to evaluate the treatment needs of first permanent molars in a
      group of schoolchildren in Mashhad. MATERIALS AND METHODS: This cross-sectional
      descriptive study was carried out on 700, 7-9 year-old students in primary
      schools in Mashhad. The schools were randomly selected from each district.
      Treatment needs and DMFT of first perma-nent molars were calculated. Data was
      analyzed using ANOVA, Chi-Square and t-test. RESULTS: A total of 95.3% of the
      children required dental treatment. Fissure sealant application and filling were
      the treat-ments most required in all age groups. The mean DMFT of first permanent
      molars was 1.31+/-1.4. It was significantly higher in girls than boys (P=0.040).
      CONCLUSION: Great treatment needs and caries prevalence in permanent first molars
      in Mashhad schoolchildren show that dental caries is still a serious problem in
      the children of our society; therefore, education of parents and teachers is
      necessary for promoting children's oral health.

PMID- 22991598
TI  - Clinical evaluation of reasons for replacement of amalgam restorations in
      patients referring to a dental school in iran.
AB  - BACKGROUND AND AIMS: The present study evaluated the most common reasons for
      replacing amalgam restorations in a university clinic. MATERIALS AND METHODS: A
      total of 217 restorations which needed to be replaced were clinically and
      radiographically evaluated in a period of 4 months. The frequencies of reasons
      for replacing amalgam restorations were calculated: The assessed items included
      recurrent caries, tooth structure fracture (functional or non-functional cusps),
      amalgam bulk fracture, amalgam marginal fracture, proximal overhangs, and
      esthetics. Data were analyzed using Fischer's exact test. RESULTS: Both in vital
      teeth and teeth which had undergone root canal therapy, the most common reason
      for amalgam replacement was cusp fracture, with the fracture of non-functional
      cusps being statistically significant. Recurrent caries was the second most
      common reason for amalgam replacement. In Class I restorations, the most common
      reasons were recurrent caries and esthetics, with no statistical significance.
      The most frequent problem in Class II restorations was fracture of non-functional
      cusps, with a statistical significance in three-surface restorations. CONCLUSION:
      According to the results, failing to reduce undermined cusps and neglectful
      caries removal are the reasons for majority of amalgam restoration replacements.
      These issues should be emphasized in the curriculum for dental students and
      continuing education courses.

PMID- 22991599
TI  - Unusual case of a talon cusp on a supernumerary tooth in association with a
      mesiodens.
AB  - Talon cusp is an accessory cusp similar to a projection, extending from the
      cingulum or cemento-enamel junction to the incisal edge. It occurs on labial or
      palatal surfaces of primary or permanent anterior teeth in both arches. This
      accessory cusp can occur as an isolated entity or in association with other
      dental anomalies. Occurrence of a talon cusp on supernu-merary teeth is rare and
      uncommon. This paper reports an unusual case of a talon cusp on a supernumerary
      tooth in association with mesiodens.

PMID- 22991600
TI  - Endodontic treatment in submerged roots: a case report.
AB  - Alveolar ridge resorption has long been considered an unavoidable consequence of
      tooth extraction. While the extent and pattern of resorption is variable among
      individuals, there is a progressive loss of ridge contour as a result of
      physiologic bone remodeling. Even today, with best modalities of tooth
      preservation, there is a group of elderly individuals who do not benefit from
      modern preventive practices and who now present a dilemma in terms of maintaining
      the masticatory apparatus necessary for nutrition. Even with excellent dental
      care, such patients experience abrasion of the natural tooth crowns with age, and
      embedded roots are left within the alveolar bone. According to old concepts of
      dental care, extraction of these roots would have been recommended, but today's
      goal of excellence in endodontics dictates otherwise. We report a case in which
      vital and non-vital root submergence was carried out to prevent alveolar ridge
      reduction.

PMID- 22991601
TI  - A technique for fabrication of an orbital prosthesis: a case report.
AB  - Rehabilitation of facial defects is a complex task, requiring an individualized
      design of the technique for each patient. The disfigurement associated with the
      loss of an eye may result in significant physical and emotional problems. Various
      treat-ment modalities are available, one of which is the use of implants.
      Although implant-supported orbital prosthesis has a su-perior outcome, it may not
      be advisable in all the patients due to economic factors. The present article
      describes a simplified technique for the fabrication of a silicone orbital
      prosthesis by constructing a custom ocular prosthesis to achieve ideal fit and
      aesthetics. Multidisciplinary management and team approach are essential in
      providing accurate and effective rehabilitation.

PMID- 22991602
TI  - Effect of Low-power Laser on Treatment of Orofacial Pain.
AB  - Low-power lasers are a group of lasers with a power less than 250 mW and unlike
      high-power lasers they have no effect on tissue temperature; they produce light
      dependent chemical reactions in tissues. These lasers have analgesic features
      with their ability to trigger reactions that reduce pain and inflammatory
      mediators. Low-power lasers can also be used instead of needles in acupuncture to
      decrease pain. Due to these features they have been used in the treatment of
      orofacial pain, including tooth hypersensitivity, post-operative flare-ups,
      mucositis, facial myalgia, temporomandibular joint disorders and neuralgia. In
      this article we review the effects of low-power lasers and their success rate in
      different studies. As the name implies (LASER: Light Amplification by the
      Stimulated Emission of Radiation), laser amplifies light by stimulated and
      excited radiation; in other words, it is amplification of excited light emission.
      Such radiation usually has some characteristic features, including mono
      chromaticity, coherency, high intensity and polarity. There are various
      classifications for lasers based on their active material (solid, fluid and gas),
      wavelength, emission type and power.

PMID- 22991603
TI  - Efficacy of application of pseudocolor filters in the detection of interproximal
      caries.
AB  - BACKGROUND AND AIMS: The aim of the present study was to compare the effect of
      application of an image processing mode of a colorizer on the efficacy of the
      detection of interproximal carious lesions viewed in direct digital radiography.
      MATERIALS AND METHODS: A total of 102 proximal surfaces of extracted human
      premolars on direct digital images were evaluated by three observers with and
      without the application of pseudocolor filter. The teeth were sectioned and
      viewed microscopically to determine the gold standard. The kappa value agreement
      ratios were calculated. RESULTS: Sensitivity and specificity values for normal
      digital and colorized images were 66.7%, 60%, 80.5%, and 50%, respectively.
      However, there were no statistically significant differences between the two
      types of images (P = 0.12). CONCLUSION: In this study application of pseudocolor
      filter on digital radiographic images failed to result in significantly improved
      caries detection.

PMID- 22991604
TI  - Proportions of maxillary anterior teeth relative to each other and to golden
      standard in tabriz dental faculty students.
AB  - BACKGROUND AND AIMS: Various methods are used to measure the size and form of the
      teeth, including the golden pro-portion, and the width-to-length ratio of central
      teeth, referred to as the golden standard. The aim of this study was to eval-uate
      the occurrence of golden standard values and golden proportion in the anterior
      teeth. MATERIALS AND METHODS: Photographs of 100 dentistry students (50 males and
      50 females) were taken under standard conditions. The visible widths and lengths
      of maxillary right and left incisors were calculated and the ratios were compared
      with golden standard. Data was analyzed using SPSS 14 software. RESULTS: Review
      of the results of the means showed statistically significant differences between
      the width ratio of right lateral teeth to the central teeth width with golden
      proportion (P<0.001). Likewise, the difference was significant for the left side,
      too (P<0.001). Test results of mean differences showed that the mean difference
      between proportion of right laterals to centrals with golden proportion was
      significant (P<0.001). The difference was significant for the left side, too
      (P<0.001). As a result, there is no golden proportion among maxillary incisors.
      The review of results of mean differences for single samples showed that the mean
      differences between the proportion of width-to-length of left and right central
      teeth was statistically significant by golden standard (P<0.001). Therefore,
      considering the width-to-length proportion of maxillary central teeth, no golden
      standard exists. CONCLUSION: In the evaluation of the width-to-width and width-to
      length proportions of maxillary incisors no golden proportions and standards were
      detected, respectively.

PMID- 22991605
TI  - Reactive hyperplasia of the oral cavity: a survey of 197 cases in tabriz,
      northwest iran.
AB  - BACKGROUND AND AIMS: Reactive hyperplastic lesions of the oral connective tissue
      are associated with injuries of soft tissue and have high prevalence rates and
      different involvement patterns in different parts of the world. The aim of this
      study was to analyze demographic data of a university department. MATERIALS AND
      METHODS: Patient records of the Department of Oral Pathology during a four-year
      period were reviewed for diagnosis of oral connective tissue reactive
      hyperplastic lesion. Data including the area involved and the type of lesion were
      collected and analyzed using descriptive statistical methods and t-test with SPSS
      15 statistical software. RESULTS: 197 cases (mean age, 37.68+/-18.97; male:
      female ratio, 1.8:1) matched study criterion. The most common affected site was
      gingiva (83.9%) and the most common lesion was fibroma (45.2%). Giant cell
      granuloma and pyogenic granuloma were more common in the maxilla than in the
      mandible. Pyogenic granuloma was seen to be equally distributed in males and
      females. CONCLUSION: The results of the present study are overall consistent with
      the findings of previous studies.

PMID- 22991606
TI  - Temporomandibular Disorders: Knowledge, Attitude and Practice among Dentists in
      Tehran, Iran.
AB  - BACKGROUND AND AIMS: Temporomandibular disorders (TMD) account for the most
      common orofacial pains rising from musculoskeletal origin. The aim of this study
      was to investigate the level of knowledge, attitudes and practice of dental
      practitioners regarding TMD in Tehran, Iran. MATERIALS AND METHODS: A
      questionnaire, containing 29 questions on etiology, signs and symptoms, diagnosis
      and treatment of TMD, was given to 200 randomly selected general dental
      practitioners and specialists as well as 11 TMD ex-perts. RESULTS: An overall
      response rate of 97% was achieved among participants (mean age: 39 +/- 8.2 years
      old; mean years in practice: 11.5 +/- 7.4). The mean score of knowledge of TMD
      was found to be 10.85+/- 2.54 (of a total of 23). TMD specialists were
      significantly more knowledgeable than general dental practitioners (p<0.05). With
      respect to attitude, there was a significant difference among various age groups,
      and by increasing age and years in practice, the attitude towards TMD had
      weakened. However, no significant difference was recorded between general dental
      practitioners' attitude and that of TMD experts towards TMD. There was a positive
      correlation between subjects' knowledge and attitude (P= 0.007, r=0.138).
      CONCLUSION: According to the results, the level of knowledge and attitude of
      general dental practitioners of Tehran regarding TMD is not desirable. The
      majority are not willing to admit and treat TMD patients.

PMID- 22991607
TI  - Effect of lengthy root canal therapy sessions on temporomandibular joint and
      masticatory muscles.
AB  - BACKGROUND AND AIMS: Trauma is one of the major factors associated with
      temporomandibular joint disorders (TMD). These disorders result from macro-trauma
      or micro-trauma. Macro-trauma might be iatrogenic; for example, from intuba-tion
      procedures, third molar extraction procedures, and lengthy dental appointments.
      The aim of this study was to evaluate the effect of lengthy root canal therapy
      (more than 2 hours) on TMJ and its supporting structures. MATERIALS AND METHODS:
      Eighty patients whose root canal therapy session lasted more than 2 hours were
      examined for the status of TMJ and masticatory muscles. After one week the second
      part of the examination was carried out for TMJ problems and pain and tenderness
      levels of masticatory muscles. Data was analyzed using Wilcoxon statistical test.
      RESULTS: Women showed more pain compared to men. There was a significant increase
      in pain in the external acoustic meatus examination one week after root canal
      therapy. Patients who were treated for their posterior teeth suffered more pain
      than those who were treated for the anteriors and premolars. Other aspects of the
      examination were not affected significantly by lengthy root canal therapy.
      CONCLUSION: Lengthy dental treatments can harm TMJ and masticatory muscles and
      wide opening of the mouth during such appointments can worsen the situation.
      Therefore, it is wise to break the appointment into shorter intervals and let the
      patients rest during treatment to close their mouth to prevent iatrogenic damage
      to TMJ.

PMID- 22991608
TI  - Severe rotational drift of an impacted mandibular third molar: a case report.
AB  - Third molar eruption is an unpredictable event. Occasionally, mandibular third
      molars undergo angular changes in young adults. This rotational drift is of
      unknown etiology, is not predictable and may facilitate the eruption or may make
      the im-paction worse. A rare case is presented with severe rotational drift of a
      mesioangularly impacted mandibular third molar.

PMID- 22991609
TI  - Bi-rooted Primary Maxillary Canines: A Case Report.
AB  - This report presents a rare case of bi-rooted primary maxillary canines. A 6-year
      old girl presented at the Department of Pediatric Dentistry, Faculty of
      Dentistry, Mashhad University of Medical Sciences, Iran, with the chief complaint
      of pain in the lower right quadrant of her dentition. Radiographic examination
      revealed bifurcation of primary maxillary canine roots. This report discusses the
      possible etiology of bi-rooted canines, implications for the developing
      dentition, and treatment options for these teeth.

PMID- 22991610
TI  - Effect of gap distance on tensile strength of preceramic base metal solder
      joints.
AB  - BACKGROUND AND AIMS: In order to fabricate prostheses with high accuracy and
      durability, soldering techniques have been introduced to clinical dentistry.
      However, these prostheses always fail at their solder joints. The purpose of this
      study was to evaluate the effect of gap distance on the tensile strength of base
      metal solder joints. MATERIALS AND METHODS: Based on ADA/ISO 9693 specifications
      for tensile test, 40 specimens were fabricated from a Ni-Cr alloy and cut at the
      midpoint of 3-mm diameter bar and placed at desired positions by a specially
      designed device. The specimens were divided into four groups of 10 samples
      according to the desired solder gap distance: Group1: 0.1mm; Group2: 0.25mm;
      Group3: 0.5mm; and Group4: 0.75mm. After soldering, specimens were tested for
      tensile strength by a universal testing machine at a cross-head speed of
      0.5mm/min with a preload of 10N. RESULTS: The mean tensile strength values of the
      groups were 162, 307.8, 206.1 and 336.7 MPa, respectively. The group with 0.75-mm
      gap had the highest and the group with 0.1-mm gap had the lowest tensile
      strength. Bonferroni test showed that Group1 and Group4 had statistically
      different values (P=0.023), but the differences between other groups were not sig
      nificant at a significance level of 0.05. CONCLUSION: There was no direct
      relationship between increasing soldering gap distance and tensile strength of
      the solder joints.

PMID- 22991611
TI  - In vitro comparison of microleakage of two materials used as pit and fissure
      sealants.
AB  - BACKGROUND AND AIMS: Marginal seal of the material is extremely important in
      fissure sealant therapy. The aim of this study was to investigate microleakage of
      flowable composite resins and conventional fissure sealants with or without
      dentin bonding agent. MATERIALS AND METHODS: The occlusal surface of 60 intact
      extracted human premolars, divided into four groups, were cleaned with
      pumice/slurry, etched with 37% phosphoric acid for 15 seconds, rinsed and dried.
      Groups were treated differ-ently: Excite bonding agent followed by Helioseal F
      fissure sealant in group1; Helioseal F alone in group 2; Excite bonding agent
      followed by Tetric Flow in group 3; and Tetric Flow alone in group 4. Light
      curing was done after each application. After thermocycling, the whole surface of
      each specimen was coated with nail varnish except for one millimeter around the
      fissure sealant. The teeth were immersed in 2% basic fuchsin for 24 hours and
      then sectioned buccolingually. The sections were analyzed for leakage under a
      stereomicroscope. Data was analyzed by Kruskal-Wallis and Mann-Whitney tests at
      asignificance level of P < 0.05. RESULTS: There were no statistically significant
      differencesbetween the study groups in terms of the mean microleakage scores (P >
      0.05), except for groups 2 and 4 (P = 0.002) and groups 3 and 4 (P = 0.033).
      CONCLUSION: Use of a flowable composite with bonding agent is a good alternative
      for sealing pits and fissures; however, further in vitro and in vivo studies are
      necessary.

PMID- 22991612
TI  - Reasons for Placement and Replacement of Resin-based Composite Restorations in
      Greece.
AB  - BACKGROUND AND AIMS: The purpose of this investigation was to assess the
      placement and replacement of resin-based composite restorations and related
      factors in a private practice in Greece. MATERIALS AND METHODS: The study
      included 1500 subjects, 720 males and 780 females, aged 18 to 52 years old. The
      clinical examination involved calculation of the number of teeth with primary
      caries and failed-restored teeth. In addition the relationship between placed and
      replaced composite restorations and the following aspects was assessed: gender,
      cavity type, tooth type and evaluation of longevity of the replaced composite
      restorations. Statistical analysis performed using the chi-square test. A p value
      less than 5% was considered statistically significant. RESULTS: The total number
      of restorations placed were 1940; 1202 of those (62%) were placed for first time
      while 738 (38%) were replaced. The main reason for the placement of new composite
      resin restorations was primary caries (60%), while secondary caries was the most
      frequent reason for the replacement (48%) of those. A statistically significant
      differ-ence was recorded between males and females regarding the composite
      restorations placed and replaced (p = 0.00082), the type of cavity of placed
      restorations (p = 0.00062), and the type of cavity of replaced ones (p =
      0.00038). The median lon-gevity of the replaced resin composite restorations was
      approximately 4 years (47%). CONCLUSION: Dental caries, primary and secondary,
      followed by tooth discoloration and loss of filling were the main rea-sons for
      placed and replaced composite restorations.

PMID- 22991613
TI  - Evaluation of gram negative bacterial contamination in dental unit water supplies
      in a university clinic in tabriz, iran.
AB  - BACKGROUND AND AIMS: Bacterial contamination of dental unit water supplies (DUWS)
      has attracted a lot of attention in recent years due to the emergence of serious
      infectionsin susceptible dental patients. The aim of the present study was to
      evaluate the presence of gram-negative bacterial contamination in DUWS at Tabriz
      University of Medical Sciences Faculty of Dentistry. MATERIALS AND METHODS: This
      descriptive study was carried out on 51 active dental units in different
      departments. Con-tamination was determined by taking samples from the unit's
      water supply before dental procedures and the use of specific culture media. The
      cultures were evaluated after 48 hours. RESULTS: Gram-negative bacterial
      contamination was identical in all the departments. In the departments on the
      ground floor, namely Departments of Periodontics and Oral and Maxillofacial
      Surgery, Pseudomonas contamination was observed in 71% of units; in the
      departments on the first floor, namely Departments of Prosthodontics,
      Orthodontics and Pedodon-tics, 46.8% of the units had Pseudomonas contamination;
      and in the departments on the second floor, namely Departments of Operative
      Dentistry and Endodontics, 37.7% of the units demonstrated Pseudomonas
      contamination. CONCLUSION: Gram-negative bacterial contamination was evident in
      the evaluated DUWS. The contamination type was identical but the number of
      contaminated units decreased with the increase in the height of the floors.

PMID- 22991614
TI  - Histopathologic Differentiation between Enchondroma and Well-differentiated
      Chondrosarcoma: Evaluating the Efficacy of Diagnostic Histologic Structures.
AB  - BACKGROUND AND AIMS: Well-differentiated chondrosarcoma and enchondroma are
      similar in histopathologic aspects; therefore, special methods should be used to
      make a distinction between these benign and malignant tumors. The aim of this
      study was to evaluate the efficacy of a histopathologic method in the long-term
      follow-up for differentiating these lesions. MATERIALS AND METHODS: The medical
      records of patients with histopathologic diagnosis of chondrosarcoma and en
      chondroma were retrieved from the Institute of Cancer, Department of Pathology
      from 1981 to 2007 in this retrospective study. A total of 14 patients with
      chondrosarcoma and 7 patients with enchondroma were included. Tumor lobulation
      pat-tern and fibrous tissue around the lesions were used for histopathologic
      differentiation between well-differentiated chon-drosarcoma and enchondroma.
      Method accuracy was evaluated by tumor recurrence in the long-term follow-up.
      RESULTS: In the well-differentiated chondrosarcoma group, the follow-up period
      was 97 months. All the patients (100%) experienced recurrence. In the enchondroma
      group, the follow-up period was 129 months. There was no recurrence in this
      group. CONCLUSION: Lobulation pattern and fibrous tissue formation around the
      tumor can be an effective and helpful indicator for histopathologic
      differentiation between enchondroma and well-differentiated chondrosarcoma.

PMID- 22991615
TI  - A localized sclerosing osteomyelitis at the periapex of a vital tooth: report of
      a misdiagnosis.
AB  - Osteomyelitis is an inflammatory infectious condition of bones, occurringeither
      acutely or chronically. The clinical course of the disease leads to destructive
      or sclerosing patterns of the involved bone. This report presents a case of
      chronic focal sclerosing osteomyelitis in a 19-year-old male with a history of an
      uncontrolled convulsive condition. The lesion was first diagnosed as an
      osteoblastoma. Chronic trauma or traumatic occlusion has the potential to induce
      osteomyelitis and should be considered a possible diagnosis in differentiating
      periapical radiopacities, even in relation with vital teeth.

PMID- 22991616
TI  - Update on prevalence of minor aphtha and the involved factors in tabriz,
      northwest iran.

PMID- 22991617
TI  - Citation analysis of papers of research projects at faculty of dentistry, tabriz
      university of medical sciences.

PMID- 22991618
TI  - Comparison of the accuracy of bracket placement with height bracket positioning
      gauge and boone gauge.
AB  - BACKGROUND AND AIMS: Diverse gauges have been used to measure and determine
      bracket height for correct bracket positioning. The aim of the present study was
      to determine and compare bracket positioning accuracy by using height bracket
      positioning gauge (HBPG) and Boone gauge (BG). MATERIALS AND METHODS: Nineteen
      sets of stone models were prepared from one patient. One set was employed to de
      termine the ideal position of brackets, and the remaining nine pairs of sets for
      bracket placement by nine clinicians usingHBPG and BG. Teeth were then sectioned
      from the stone models and placed inside acrylic molds; photographs were takenand
      imported to a computer. In two groups, the position of each bonded bracket was
      compared in three aspects of vertical, mesiodistal and angular with the ideal
      position of every bracket. Finally, bracket positioning errors were measured.
      RESULTS: Mann-Whitney U test demonstrated significant differences in the means
      ofvertical error between the HBPG group and BG groups (P<0.001), while there were
      no significant differences between mesiodistal and angular errors. Facto-rial
      ANOVA revealed that gauge and tooth type, and the position of tooth on the right
      and left side of the mouth play a ma-jor role in the rate of vertical error.
      CONCLUSION: Vertical accuracy of bracket positioning by the use of HBPG is more
      than that by BG. However, there is no difference between two gauges in relation
      to the mesiodistal and angular errors.

PMID- 22991619
TI  - Impact of temperament on child behavior in the dental setting.
AB  - BACKGROUND AND AIMS: Temperament has been suggested to be a predictive factor for
      the child's reaction to dental treatment especially in young ages. The aim of
      this study was to assess the relationship between temperament and child behavior
      in relation to age in the dental setting. MATERIALS AND METHODS: In this
      descriptive-analytical study, 190 children, aged 1 to 7years, who visited dentist
      for the first time, were included. Early Childhood Behavior Questionnaire (ECBQ)
      for 18-36 month-olds and Child Behavioral Questionnaire (CBQ) for 3-7 year-old
      children were completed. Child behavior was rated during dental treatmentusing
      Frankl scale. Kolmogorov-Smirnov test was used to examine normal distribution of
      the population. The data were analyzed using descriptive statistics and ANOVA,
      Chi Square and Pearson's correlation coefficient. P< 0.05 was considered as sig
      nificance level. RESULTS: 58 children (29.6%) had completely negative behavior
      and 27 children (13.8%) had completely positive behaviorduring the treatment. 65%
      of the children aged 1 to 3 years had completely negative behavior while this
      figure was 20% for the children aged 6 to 7 years. Temperament score for the
      children with completely positive behavior was 257.95 while it was 299.37 for
      children with completely negative behavior. As the temperament score increased,
      child behavior rank waslower. CONCLUSION: Age and temperament seem to act as
      predictors of child behavior in the dental setting.

PMID- 22991620
TI  - Temporomandibular Disorders and Related Factors in a Group of Iranian
      Adolescents: A Cross-sectional Survey.
AB  - BACKGROUND AND AIMS: Temporomandibular disorders (TMDs) are the most common
      condition affecting the tem-poromandibular joint and associated structures. The
      aim of this study was the epidemiologic evaluation of TMDs and re-lated factors
      in a group of Iranian adolescents. MATERIALS AND METHODS: This descriptive cross
      sectional survey included a sample of800 high school students (400 girls and 400
      boys) aged 14 to18 years, in Mashhad, Iran, selected using cluster sampling.
      Examiners completed question-naires and performed the clinical examinations. Data
      were analyzed with the Chi-square and Fisher exact tests. RESULTS: The prevalence
      of TMDs in the studied sample was 34.7%. The most common signs of TMDs were
      clicking, muscle tenderness and TMJ tenderness. The most prevalent predisposing
      factors of TMDs were clenching, premature con-tact in protrusive movement and
      bruxism. A clear predominance was seen in girls (40.5%) compared with boys (29%)
      (P = 0.001). CONCLUSION: Signs and symptoms of TMDs were prevalent in Iranian
      adolescents with a clear female predominance.

PMID- 22991621
TI  - Survey of reactive hyperplastic lesions of the oral cavity in mashhad, northeast
      iran.
AB  - BACKGROUND AND AIMS: Reactive hyperplasias (RHs) are common oral mucosal lesions
      caused by irritation of the mu-cosa. The aim of this study was to evaluate the
      frequencies of various types of oral RHs in a university clinic. MATERIALS AND
      METHODS: Oral RH cases, undergone biopsy in a four-year period, were studied
      retrospectively. Data including age and gender as well as the location and
      clinical characteristics of the lesion were collected and analyzed. RESULTS: A
      total of 123 cases (age range 7-79 years old; mean: 38.8 +/- 18.50 years; male:
      female ratio, 1.9:1) were evalu-ated. Over a half of the lesions including
      pyogenic granuloma, giant cell granuloma, and peripheral ossifying fibroma were
      found in gingiva (52%). Fibroma involved mostly the buccal mucosa. Most lesions
      had smooth surface and sessile base. CONCLUSION: The clinical features of oral
      inflammatory hyperplasia in the studied sample were similar to those previously
      reported.

PMID- 22991622
TI  - Fluoride concentration of bottled water and tap water in tehran, iran.
AB  - BACKGROUND AND AIMS: As a result of poor quality of public water supply in many
      countries, people have recently turned to bottled water consumption, the fluoride
      content of which is not generally consistent among different brands. This study
      sought to measure the fluoride concentration of public water supply in comparison
      with commercial brands of min-eral bottled water available in Tehran, Iran.
      MATERIALS AND METHODS: Eight different brands of locally produced bottled mineral
      water and samples of tap water were evaluated for fluoride content. All samples
      were collected in five equal containers in two summer and winter seasons. The
      fluoride content in part per million (ppm) was determined using a fluoride Ion
      Selective Electrode. The data were ana-lyzed using two-way ANOVA. For comparison
      of the fluoride content between three different brands of bottled water, one-way
      ANOVA was employed. Sample t-test was used to compare the label and laboratory
      values of bottled water. RESULTS: The highest concentration of fluoride in a
      bottled water brand was found to be 0.409 ppm with a pH of 6.67 in summer. There
      was a significant difference between the mean fluoride level of tap water (0.229
      +/- 0.079 ppm) and bottled water (0.111 +/- 0.122 ppm) (P < 0.001). The measured
      fluoride concentrations of bottled water were significantly lower than those
      printed on the labels (P < 0.001). CONCLUSION: Our findings revealed that the
      mean fluoride level of both bottled and tap water samples evaluated is con
      siderably lower than accepted standards.

PMID- 22991623
TI  - Nonsurgical treatment of maxillary deficiency using tongue guard appliance: a
      case report.
AB  - The present report describes orthodontic treatment of a patient with skeletal
      Class III malocclusion and maxillary hypopla-sia. To correct the retrusive
      maxilla, the treatment plan included an intra-oral removable device. It had the
      advantages of good patient cooperation, ease of construction and effective
      modification. Forward growth of the maxilla, minimal down-ward and backward
      rotation of the mandible and improved facial profile esthetics were achieved.

PMID- 22991624
TI  - A Rare Case of Myoepithelioma around the Left Orbit.
AB  - Myoepithelioma is a rare neoplasm of the salivary glands, generally occurring in
      the parotid gland and less often in the mi-nor accessory salivary glands of the
      oral cavity. It is known to be a rare entity occurring at unusual locations,
      which makes it difficult to diagnose. Such a rare case of myoepithelioma in
      salivary glands present at an unusual location around the left orbit is presented
      here.

PMID- 22991625
TI  - A Case of Thrombocytopenia due to Odontogenic Infection.
AB  - Thrombocytopenia in surgical patients is a potentially serious condition,faced by
      surgeons. A close relationship between sepsis and thrombocytopenia has been
      suggested. Thrombocytopenia has even been suggested to be indicative of an acute
      infection. Platelet count in a septicemic patient may also serve as a prognostic
      tool. There are many reports of thrombocy-topenia due to septicemia in the
      literature but the occurrence of thrombocytopenia in maxillofacial infections is
      rare. Thrombocytopenia in a patient with odontogenic infection presents unique
      diagnostic and management challenges. A case report of an adult male patient with
      odontogenic infection, who developed life-threatening thrombocytopenia, is
      presented.

PMID- 22991626
TI  - Evaluation of Cone Beam Computed Tomography (CBCT) System: Comparison with
      Intraoral Periapical Radiography in Proximal Caries Detection.
AB  - BACKGROUND AND AIMS: With the introduction of Cone Beam Computed Tomography
      (CBCT) in dentistry, a question has been raised whether the technique
      significantly increases the diagnostic accuracy in comparison with other
      techniques or not. Therefore, the present study was undertaken to assess the
      accuracy of CBCT modality in detecting proximal carious lesions as compared to
      conventional periapical radiographs. MATERIALS AND METHODS: This diagnostic study
      was carried out on 84 human extracted molars and premolars. The teeth were
      mounted and divided in 28 blocks of 3 teeth. Periapical and CBCT images of teeth
      were obtained. Five observers scored the images for the detection of proximal
      carious lesions using a 2-point scale (caries, present; caries, absent). The gold
      standard was determined by histopathologic sections. Sensitivity, specificity,
      PPV, NPV and receiver operating charac-teristics (ROC) curves were traced for
      observers in both systems. The results were analyzed by paired t-test. RESULTS:
      The area under the ROC curve, sensitivity, specificity, accuracy, positive and
      negative predictive values of CBCT images were 0.568, 0.835, 0.637, 0.714, 0.598
      and 0.856, respectively. These parameters were 0.432, 0.837, 0.722, 0.77, 0.687
      and 0.858 for the periapical conventional technique, respectively. CONCLUSION:
      The CBCT images did not enhance detection of proximal caries in comparison with
      periapical images.

PMID- 22991627
TI  - Doppler sonography confirmation in patients showing calcified carotid artery
      atheroma in panoramic radiography and evaluation of related risk factors.
AB  - BACKGROUND AND AIMS: The purpose of this study was to identify patients at the
      risk of cerebrovascular attack (CVA) by detecting calcified carotid artery
      atheroma (CCAA) in panoramic radiography and evaluating their risk factors.
      MATERIALS AND METHODS: A total of 960 panoramic radiographs of patients above 40
      years old were evaluated. Doppler Sonography (DS) was performed for patients who
      showed calcified carotid artery atheroma (CCAA) in panoramic radiogra-phy in
      order to determine the presence of CCAA and the degree of stenosis.
      Cardiovascular risk factors in both groups of patients with CCAA (12 subjects)
      and without CCAA (3 subjects) were compared using a questionnaire filled out by
      the patients. Statistical analysis including Fisher and independent t-test
      applied for data analysis. RESULTS: Fifteen patients (30 sides) showed
      calcification in their panoramic radiographs, and underwent DS which revealed
      CCAA in 16 sides (12 patients). Two patients (13.33%) showed stenosis greater
      than 70%. Among the risk factors, only age showed a significant association with
      the occurrence of carotid calcified atheroma (P=0.026). CONCLUSION: Considering
      the results, dentists should refer especially elderly patients with
      radiographically identified atheromas for further examinations, as asymptomatic
      CCAA might be associated with high degrees of stenosis.

PMID- 22991628
TI  - Fracture Resistance of Composite Fixed Partial Dentures Reinforced with Pre
      impregnated and Non-impregnated Fibers.
AB  - BACKGROUND AND AIMS: The mechanical properties of fiber-reinforced composite
      fixed partial dentures (FPDs) are af-fected by fiber impregnation. The aim of
      this in vitro study was to compare the fracture resistance of composite fixed
      partialdentures reinforced with pre-impregnated and non-impregnated fibers.
      MATERIALS AND METHODS: Groups (n=5) of three-unit fiber-reinforced composite FPDs
      (23 mm in length) from maxillary second premolar to maxillary second molar were
      fabricated on two abutments with pontic width of 12 mm. One group was fabricated
      as the control group with composite (Gradia) and the other two groups were
      fabricated with composite (Gradia) reinforced with pre-impregnated fiber (Fibrex
      ribbon) and non-impregnated fiber (Fiber braid), respectively. The specimens were
      stored in distilled water for one week at 37 degrees C and then tested in a
      universal testing machine by means of a three-point bending test. Statistical
      analysis consisted of one-way ANOVA and a post hoc Scheffe's test for the test
      groups (alpha=0.05). RESULTS: Fracture resistance (N) differed significantly
      between the control group and the other two groups (P<0.001), but there were no
      statistically significant differences between the pre-impregnated and non
      impregnated groups (P=0.565). The degree of deflection measured (mm) did not
      differ significantly between the three groups (P=0.397), yet the mean deflection
      measured in pre-impregnated group was twice as that in the other two groups.
      CONCLUSION: Reinforcement of composite with fiber might considerably increase the
      fracture resistance of FPDs; how-ever, the type of the fiber used resulted in no
      significant difference in fracture resistance of FPD specimens.

PMID- 22991629
TI  - Nucleolar organizer regions in oral squamous cell carcinoma.
AB  - BACKGROUND AND AIMS: Several diagnostic methods are being employed to detect
      benign and malignant lesions, one of which is silver nitrate staining for
      organizer regions. The number of nucleolar organizing regions (NORs) can be used
      to show the degree of cell activity or metabolism in pathologic lesions. This
      study was designed to evaluate NORs as determi-nants of precancerous and squamous
      cell carcinoma. MATERIALS AND METHODS: A silver colloid technique was applied on
      paraffin sections of 40 cases of oral squamous cell carcinoma and 25 cases of
      precancerous lesions; 15 specimens of normal epithelium were selected for the
      control group. After staining with silver nitrate, argyrophilic nucleolar
      organizer regions (AgNORs) were counted in 100 epithelial cells in three groups
      with the use of an oil immersion and *1000 objective lens. One-way ANOVA and a
      post hoc Tukey test were used for statistical analysis. RESULTS: The mean numbers
      and standard deviations of AgNORs were 1.58 +/- 0.76 in normal epithelium, 2.1 +/
      1.05 in pre-cancerous lesions and 2.43 +/-1.33 in squamous cell carcinoma (SCC).
      There were statistically significant differences in Ag-NORs numbers between the
      groups (P<0.001) and significant differences in precancerous lesions between
      dysplastic and non-dysplastic epithelia (P<0.001). The mean AgNORs count per
      nucleus increased from healthy epithelium to precancer-ous lesion to SCC.
      CONCLUSION: This study suggests that the silver staining technique for the
      detection of NORs (AgNOR) can be used to distinguish precancerous lesions and
      benign and malignant lesions.

PMID- 22991630
TI  - Prevalence of taurodontism in premolars and molars in the South of iran.
AB  - BACKGROUND AND AIMS: The study was undertaken to assess the prevalence of
      taurodontism and related systemic condi-tions and gender differences in premolars
      and molars of patients attending Shiraz Faculty of Dentistry. MATERIALS AND
      METHODS: In this cross-sectional study, panoramic radiographs of 510 randomly
      selected patients were evaluated by a maxillofacial radiologist for the apically
      displaced pulp chamber. Detailed medical and family history of the patients was
      obtained. RESULTS: The prevalence of taurodontism in 510 panoramic views was 5.5%
      of patients. Females had significantly higher prevalence of taurodontism than men
      (P>0.05) and mandibular second molar was the most affected tooth. CONCLUSION:
      Taurodontism was relatively common in population under study. A family history of
      other anomalies should be checked for affected patients.

PMID- 22991631
TI  - Awareness of Orthodontic Treatments among School Teachers of Two Cities in Iran.
AB  - BACKGROUND AND AIMS: Since most orthodontic patients are children and
      adolescents, it is believed that teachers can help find these patients and make
      them aware of their orthodontic problems. Therefore, teachers are expected to
      have proper knowledge about these problems. The aim of this study was to
      determine teachers' awareness about orthodontic treatments in Tabriz and Saqqez
      and compare it in different educational levels. MATERIALS AND METHODS: A
      questionnaire was given to 384 teachers (204 in Tabriz and 180 in Saqqez) in
      randomly selected schools of different levels. The questionnaire had 17 questions
      in 3 sections, including general information, age, and costs of orthodontic
      treatments. The teachers' awareness in two cities was analyzed with independent t
      test and in edu-cational levels with one-way ANOVA. RESULTS: About 94% of the
      participants believed orthodontic treatment consisted of arrangement of teeth
      with special braces. However, there was no significant difference between the two
      cities in general information (p=0.23) and the age suitable for orthodontic
      treatment (p=0.53). The differences in the teachers' awareness in three
      educational levels were not statistically significant between the two cities
      (p=0.23). CONCLUSION: Awareness of teachers about orthodontic treatment in Saqqez
      and Tabriz was not sufficient and different; 75% of the participants believed
      that high cost of orthodontic treatment is the main problem.

PMID- 22991632
TI  - Squamous cell carcinoma arising from an oral lichenoid lesion: a case report.
AB  - Lichenoid reactions represent a family of lesions with different etiologic
      factors and a common clinical and histologic ap-pearance. Lichen planus is
      included with lichenoid reactions and is a relatively common chronic
      mucocutaneous disorder. The most important complication of lichenoid reactions is
      the possibility of malignant transformation. That is why it has been considered a
      precancerous condition. Although the malignant transformation rate varies widely
      in the literature, from 0.4 to 6.5 percent, in most studies it does not exceed
      1%. The aim of this paper is to report a rare case of squamous cell car-cinoma
      (SCC) arising within an oral lichenoid lesion in a 17-year-old woman, where SCC
      is very uncommon. The patient did not have any risk factors and was healthy. The
      lesion was located on the border of the tongue. In view of thecommon occurrence
      of OLP (oral lichen planus) and the unresolved issues regarding its premalignant
      potential, this case report illus-trates the need for histologic confirmation and
      a close follow-up of clinical lesions with lichenoid features.

PMID- 22991633
TI  - Pemphigus Vulgaris Associated with Rheumatoid Arthritis in a Patient not Taking
      Penicillamine.
AB  - D-penicillamine is one of the disease-modifying anti-rheumatic drugs (DMARDs).
      Drug-induced pemphigus is not fre-quently associated with D-penicillamine, and to
      date, the number of reported cases is about a hundred. Most reports of D
      penicillamine-induced pemphigus vulgaris are in patients with rheumatoid
      arthritis. It has rarely been reported in patients not taking D-penicillamine. We
      report a case of pemphigus vulgaris in a 48-year-old female patient with
      rheumatoid arthri-tis, not taking penicillamine.

PMID- 22991634
TI  - Finite Element Analysis of Soft-lined Mandibular Complete Denture and its
      Supporting Structures.
AB  - BACKGROUND AND AIMS: There are many edentulous people with severely resorbed
      residual ridges and non-resilient lin-ing mucosa that are unable to tolerate
      occlusal forces during functional and parafunctional movements. Lining the tissue
      surface of dentures with a flexible material can theoretically distribute and
      absorb forces with cushioning effect. The aim of this study was to evaluate the
      effect of a soft liner on stress levels in mandibular complete denture and its
      supporting struc-tures by finite element analysis. MATERIALS AND METHODS: A
      simplified 3-dimensional finite element model of relatively resorbed mandible,
      mucosa, denture and a soft liner was prepared. Then the model, with and without
      soft liner, underwent normal vertical and lateral occlusal forces. The stresses
      were analyzed using the ANSYS 12 software. RESULTS: Using the soft liner
      increased stress levels up to 18.5% and 30% in the cortical bone and mucosa,
      respectively, after vertical load was applied in the incisor region. Application
      of bilateral vertical load on the molar area increased stress in cortical bone u
      to 44% and in the mucosa up to 29%. Unilateral loading in the canine area
      increased stress level in the mucosa up to 63.5%. The highest stress was seen at
      denture base followed by the cortical bone. CONCLUSION: Use of soft liners
      increased stress in denture supporting structures. Higher level of stress
      concentration was observed primarily in the denture base followed by the cortical
      bone.

PMID- 22991635
TI  - Marginal and internal fit of CAD/CAM and slip-cast made zirconia copings.
AB  - BACKGROUND AND AIMS: CAD/CAM systems facilitate the use of zirconia substructure
      materials for all-ceramic copings. This in vitro study investigated the marginal
      and internal fit of zirconia copings made with CAD/CAM system and slip-casting
      method. MATERIALS AND METHODS: Sixteen CAD/CAM made zirconia copings and 16 slip
      cast made zirconia copings were fabri-cated and cemented with glass-ionomer
      cement to their respective master abutment models, and thickness of the cement
      layer was measured at specific measuring points with stereomicroscope. RESULTS:
      In the left wall, the mean axial internal gap was greater in group one than group
      two (62.49 vs. 48.14) (P =0.007), in the right wall the mean axial internal gap
      was greater in group one than group two (44.87 vs. 40.91) (P = 0.465). The oc
      clusal internal gap was greater in group one than group two (118.81 vs. 102.11)
      (P =0.423). The mean marginal gap also was greater in group one than group two
      (46.67 vs. 44.29) (P = 0.863). The differences in marginal fit between these two
      methods were not statistically significant, except for left axial internal gap
      that was significantly greater in the CAD/CAM system than conventional slip-cast
      technique (P =0.007). CONCLUSION: It was concluded that this CAD/CAM system can
      compete well with conventional systems for clinical fit, and can achieve good in
      vitro marginal fit.

PMID- 22991636
TI  - Beam Hardening Artifacts: Comparison between Two Cone Beam Computed Tomography
      Scanners.
AB  - BACKGROUND AND AIMS: At present, cone beam computed tomography (CBCT) has become
      a substitute for computed tomography (CT) in dental procedures. The metallic
      materials used in dentistry can produce artifacts due to the beam hard-ening
      phenomenon. These artifacts decrease the quality of images. In the present study,
      the number of artifacts as a result of beam hardening in the images of dental
      implants was compared between two NewTom VG and Planmeca Promax 3D Max CBCT
      machines. MATERIALS AND METHODS: An implant drilling model was used in the
      present study. The implants (Dentis) were placed in the canine, premolar and
      molar areas. Scanning procedures were carried out by two CBCT machines. The
      corresponding sections (coronal and axial) of the implants were evaluated by two
      radiologists. The number of artifacts in each image was determined using the
      scale provided. Mann-Whitney U test was used for two-by-two comparisons at a
      significance level of P<0.05. RESULTS: There were statistically significant
      differences in beam hardening artifacts in axial and coronal sections between the
      two x-ray machines (P<0.001), with a higher quality in the images produced by the
      NewTom VG. CONCLUSION: Given the higher quality of the images produced by the
      NewTom VG x-ray machine, it is recommended for imaging of patients with extensive
      restorations, multiple prostheses or previous implant treatments.

PMID- 22991637
TI  - Comparison of Accuracy of Conventional Periapical Radiography and Direct Digital
      Subtractions Radiography with or without Image Enhancement in the Diagnosis of
      Density Changes.
AB  - BACKGROUND AND AIMS: In periapical radiographic technique, the changes will be
      visible only after considerable deposi-tion or resorption while digital
      subtraction technique visualizes slight density changes. This study was aimed to
      compare visualization of density changes in conventional periapical radiographs
      and digital subtraction technique with or without image enhancement. MATERIALS
      AND METHODS: Three dry human mandibles with unspecified age and gender were
      selected. Conventional periapical and direct digital radiographs were taken from
      the anterior, and right and left posterior regions by step-wise placement of
      aluminum plates until the image of the plate was clearly visible. The radiographs
      taken with the direct digital technique were subtracted from the first radiograph
      using Photoshop software. Three observers evaluated the radiographs and the
      digital subtraction images with or without image enhancement. The density was
      recorded in each radiograph in which the image of the aluminum plate was
      completely visible. RESULTS: In all mandibles, the differences in diagnosis of
      densitychanges between the conventional periapical radiographic technique and the
      direct digital subtraction radiographic technique with or without image
      enhancement were statistically significant irrespective of the region under study
      (p<0.001). There were no significant differences in the diagnosis of density
      changes in all the three mandibles in the left and right posterior regions
      between the two radiographic techniques. However, the differences in the anterior
      region were statistically significant (p<0.001). CONCLUSION: Direct digital
      subtraction radiographic technique with or without image enhancement is a more
      efficacious technique in exhibiting minor density changes compared to
      conventional periapical radiographic technique.

PMID- 22991638
TI  - Effect of Ascorbic Acid on Shear Bond Strength of Orthodontic Brackets Bonded
      with Resin-modified Glass-ionomer Cement to Bleached Teeth.
AB  - BACKGROUND AND AIMS: Bleaching can considerably reduce shear bond strength (SBS)
      of orthodontic brackets bonded with composite adhesives. Application of
      antioxidants is a method to reverse the negative effect of bleaching on composite
      to-enamel bond. However, the efficacy of antioxidants in increasing the SBS of
      brackets bonded using resin-modified glass-ionomer cement (RMGIC) has not been
      studied, which was the aim of this study. MATERIALS AND METHODS: Fifty freshly
      extracted human maxillary first premolars were bleached with 35% hydrogen
      peroxide (Pola Office Bleaching, SDI). Sodium ascorbate 10% was applied to the
      experimental specimens (n=25). All the specimens were etched with 37% phosphoric
      acid (Ivoclar/Vivadent) and bonded using RMGIC (Fuji Ortho LC, GC). The specimens
      were subjected to incubation (37 degrees C, 24h) and thermocycling (1000 cycles,
      5-55 degrees C, dwell time = 1 min). The SBS was measured at 0.5 mm/min debonding
      crosshead speed. The adhesive remnant index (ARI) was scored under *10 magni
      fication. Data were analyzed using Mann-Whitney U test, one- and independent
      samples t-test, and Fisher'sexact test (alpha=0.05). RESULTS: The mean SBS of
      experimental and control groups were 11.97 +/- 4.49 and 7.7 +/- 3.19 MPa,
      respectively. The dif-ference was statistically significant (P=0.000 by t-test).
      SBS of both control (P=0.014) and experimental (P=0.000) groups were
      significantly higher than the minimum acceptable SBS of 6 MPa, according to one
      sample t-test. CONCLUSION: Application of ascorbic acid can guarantee a strong
      bond when RMGIC is to be used. However, RMGIC might tolerate the negative effect
      of bleaching with minimum SA treatments (or perhaps without treatments), which de
      serves further studies.

PMID- 22991639
TI  - Effect of different prophylaxis methods on microleakage of microfilled composite
      restorations.
AB  - BACKGROUND AND AIMS: This study was aimed at evaluating the effect of different
      prophylaxis methods on microleak-age of microfilled composite restorations.
      MATERIALS AND METHODS: In this in vitro study, class V cavities were prepared on
      buccal surfaces of 84 bovine teeth. The teeth were restored with Tetric N-Bond
      adhesive and Heliomolar composite resin. Subsequent to a thermocycling procedure
      and three months of storage in distilled water, the teeth were randomly assigned
      to four groups (n=21): (1) prophylaxis with a rubber cup and pumice; (2)
      prophylaxis with a brush and pumice; (3) prophylaxis with air/powder polishing
      device; and (4) no prophylaxis (the control group). Then the teeth were immersed
      in 2% basic fuchsin for 24 hours and sectioned for microleakage evaluation under
      a stereomicroscope. Data were analyzed using Kruskal-Wallis and Wilcoxon Signed
      Rankstests. Statistical significance was defined at p<0.05. RESULTS: There were
      no statistically significant differences in occlusal and gingival microleakage
      between the groups (p=0.996 and p=0.860, respectively). In all the groups
      gingival margins exhibited significantly higher microleakage values compared to
      occlusal margins (p<0.0005). CONCLUSION: Prophylaxis methods had no adverse
      effect on marginal leakage of microfilled composite resin restorations.

PMID- 22991640
TI  - Dental Fear and Concomitant Factors in 3-6 Year-old Children.
AB  - BACKGROUND AND AIMS: Dental fear/anxiety as a barrier in accessing oral health
      care is poorly investigated in Iranian children. The aims of this study were to
      evaluate the prevalence of dental fear and behavior management problems, as well
      as to examine the relationship between dental fear/anxiety and probable
      concomitant factors. MATERIALS AND METHODS: Mothers of 200 children aged 3-6 were
      participated in this descriptive-analytic study, and completed the CFSS-DS, SDQ,
      Chora and Spielberger questionnaires for both child and parents' general and
      dental anxiety in this descriptive- analytic study. Behavior was evaluated
      according to Frankl scale. Statistical approaches included T-test, chi-sq, and
      Pearson Linear correlation. RESULTS: The mean score of dental fear was 32.15 +/-
      10 and the prevalence was 22.2%. Significant correlations were found between
      child's dental fear, general fear and behavior management problems; however, no
      relationship was found between child's dental fear and parental dental or general
      fear. CONCLUSION: According to results of this study dental fear/anxiety seems to
      be more conditional and related to child's temperament than parental impact.
      Parental evaluation of dental fear can be used as a predictor of child's dental
      behavior.

PMID- 22991641
TI  - Nonsurgical endodontic retreatment of maxillary second molar with two palatal
      root canals: a case report.
AB  - Successful endodontic treatment requires thorough knowledge regarding each root
      canal system of any tooth and probability of extra canals should be considered.
      Second maxillary molar with two palatal root canals is not frequent and its
      incidence reported in literatures is about 0.4-2%. The present case report
      describes non-surgical retreatment of maxillary second mo-lar with two palatal
      root canals. Radiographic interpretation is difficult in this region; so, very
      careful examination of pulpal space and using supportive devices such as loupe
      and operating microscope is recommended to discover any unusual anat-omic
      features like extra canals.

PMID- 22991643
TI  - Root and canal morphology of mandibular third molars in an Iranian population.
AB  - BACKGROUND AND AIMS: A through knowledge of the root canal morphology is required
      for successful endodontic ther-apy. The aim of this study was to investigate the
      root and canal morphology of mandibular third molars in Kerman, a prov-ince in
      southeast of Iran. MATERIALS AND METHODS: One-hundred-fifty extracted mandibular
      third molars were collected randomly from different dental clinics in Kerman. The
      root canal anatomy and morphology of each tooth was carefully studied using a
      clearing tech-nique. Root number and morphology, number of canals per root, root
      canal configuration according to Vertucci classifica-tion, and incidence of
      dilacerated roots and C-shaped canals in mandibular third molars were evaluated
      under stereomicro-scope with *2 to *3 magnifications. RESULTS: From the total of
      150 mandibular third molars studied, 21% had one root. The majority of teeth
      (73%) had two roots. 5.5% of the teeth had three roots. The incidence of C-shaped
      canal was 3.5% in this study and 8% of the teeth had at least one dilacerated
      root. CONCLUSION: Although root canal anatomy and morphology of mandibular third
      molars is very variable having two roots seems to be the normal anatomy for these
      teeth.

PMID- 22991642
TI  - Effect of Duration of Irrigation with Sodium Hypochlorite in Clinical Protocol of
      MTAD on Removal of Smear Layer and Creating Dentinal Erosion.
AB  - BACKGROUND AND AIMS: The aim of the present study was to compare 1.3% sodium
      hypochlorite (NaOCl) in MTAD (mixture of tetracycline isomer, acid, and
      detergent) for the removal of the smear layer and induction of canal erosion.
      MATERIALS AND METHODS: 38 maxillary incisors were divided in three experimental
      groups of 10 and two positive and negative control groups of each 4 teeth, and
      prepared using rotary files. In test groups, 1.3% NaOCl was used for 5, 10 and 20
      minutes during preparation followed by MTAD as the final rinse. In negative
      control group, 5.25% NaOCl was used for 10 minutes followed by 17%
      Ethylenediamine Tetra-Acetic Acid (EDTA) as the final rinse. In positive control
      group, dis-tilled water was used for 10 minutes during preparation and then as
      the final rinse. The samples were examined under scan-ning electron microscope,
      and the smear layer and dentinal erosion scores were recorded. RESULTS: Five and
      10 min groups had significant differences with 20 min group (p < 0.05). In apical
      third, 5 and 10 min groups had also significant differences with 20 min (p <
      0.05). In the coronal thirds, when the time of irrigation with 1.3% NaOCl
      increased from 5 min to 20 min, erosion also increased significantly. However, 5
      and 10 min groups had no signifi-cant differences with negative control group.
      CONCLUSION: The use of 1.3% sodium hypochlorite for 5 and 10 minutes in the MTAD
      protocol removes the smear layer in the coronal and middle thirds but does not
      induce erosion.

PMID- 22991644
TI  - Comparison of the effect of three cements on prevention of enamel
      demineralization adjacent to orthodontic bands.
AB  - BACKGROUND AND AIMS: This in vitro study was designed to compare enamel
      demineralization depths adjacent to bands cemented with zinc polycarboxylate,
      glass ionomer (GI) and resin-modified glass ionomer (RMGI), in order to achieve
      minimal enamel demineralization during orthodontic treatment. MATERIALS AND
      METHODS: Sixty fully developed extracted third molars were randomly divided into
      three testgroups each containing 20 samples, used to cement orthodontic bands
      with zinc polycarboxylate, GI and RMGI. All samples were demineralized using
      White method using hydroxyapatite, latic acid and Carbapol for in vitro caries
      simulation, and then, immersed in 10% solution of methylene blue. The mean depth
      of dye penetration was assessed up to 0.1 millimeter, reflect-ing the depth of
      enamel demineralization. One way ANOVA and LSD statistical tests were employed to
      evaluate significant differences among groups. RESULTS: The highest dye
      penetration depth was seen in zinc polycarboxylate group, followed by GI, and
      RMGI groups, respectively, with significant differences among each two groups (P
      < 0.05). CONCLUSION: The use of RMGI cement seems to present significantly better
      prevention of enamel demineralization adja-cent to orthodontics bands.

PMID- 22991645
TI  - Marginal Microleakage of Low-shrinkage Composite Silorane in Primary Teeth: An In
      Vitro Study.
AB  - BACKGROUND AND AIMS: Despite the increasing demand for adhesive restorations in
      pediatric dentistry, polymerization shrinkage and subsequent marginal
      microleakage remains a problem. The aim of this study was to evaluate of the
      sealing ability of novel low-shrinkage composite silorane in class V cavity of
      primary canines in comparison with three types of composite resin. MATERIALS AND
      METHODS: Ninety-one non-carious extracted primary canines were randomly divided
      in six groups (n=15). Standard class V cavities were prepared on the buccal
      surface of each tooth that the occlusal margin was in the enamel and the cervical
      margin extending 1 mm below the cemento-enamel junction. The preparations were
      restored with the different composite materials in normal consistency with
      application the bonding in six groups (Filtek silorane; etch + Filtek Silorane;
      Z250; Filtek supreme; els saremco; Aelite LS). Teeth were then exposed to thermal
      cycles (1000 cycles, 5 degrees C and 55 degrees C), sealed and immersed in a 0.5%
      basic fuchsine for 24 hours, and finally sectioned. Buccolingual and mar-ginal
      leakage was assessed with dye penetration. RESULTS: The best seal were obtained
      with etch + Filtek Silorane (P < 0.05) and the weakest seal with Z250 composite
      res-torations (P > 0.05). Except for etch + silorane, there was no significant
      differences in sealing ability (P > 0.05), and in the microleakage degree at the
      cementum and enamel margins (P > 0.05) between the groups. CONCLUSION: According
      to the results, low-shrinkage silorane composite restorations with etching the
      cavity provide the highest seal in primary teeth.

PMID- 22991646
TI  - Effect of Abutment Height on Retention of Single Cement-retained, Wide- and
      Narrow-platform Implant-supported Restorations.
AB  - BACKGROUND AND AIMS: In contrast to prepared natural dentin abutments,little is
      known concerning factors influencing the retention of fixed prostheses cemented
      to implant abutments. The aim of this study was to investigate the effect of im
      plant abutment height on the retention of single castings cemented to wide and
      narrow platform implant abutments. MATERIALS AND METHODS: Thirty-six parallel
      sided abutments (Biohorizon Straight Abutment) of narrow platform (NP) and wide
      platform (WP) sizes with their analogs were used. In each group of platform size,
      abutments were prepared with axial wall heights of 5, 4, 3, 2 mm (n=9). On the
      whole 72 castings were constructed, which incorporated an attachment to allow
      removal. Castings were cemented to abutments with TempBond(r). A uniaxial tensile
      force was applied to the crown using an Instron machine until cement failure
      occurred. Analysis of variance of the models were fit to determine the effect of
      height of abutment of the restorations on the mean tensile strength (alpha=0.05).
      RESULTS: The mean peak removal force for corresponding abutments was
      significantly different (P < 0.05): (1) with plat-form sizes: WP > NP; (2) with
      alteration of axial wall height for NP: 5 mm > 4 mm > 3 mm = 2 mm and for WP: 5
      mm > 4 mm = 3 mm = 2 mm. CONCLUSION: The retention of NP cement-retained
      restorations is influenced by the wall height but not in same manner as WP.
      Restorations of narrow-platform size with longer abutment exhibited higher
      tensile resistance to dislodgement.

PMID- 22991647
TI  - Vascular endothelial growth factor and ki-67 antigen expression in relation to
      age and gender in oral squamous cell carcinoma.
AB  - BACKGROUND AND AIMS: Vascular endothelial growth factor (VEGF) and Ki-67 antigen
      are contributing factors in this process cell proliferation and new blood vessels
      formation in tumor progression. This study was conducted to examine the
      relationship between the expression of VEGF and Ki-67 and gender and age of
      patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Twenty
      three archival samples of well-differentiated OSCC were examined immunohisto
      chemically and assessed by obtaining Total Score (TS = proportion score *
      staining index). For statistical analysis, t-test and Pearson's correlation were
      employed. P<=0.05 was considered statistically significant. RESULTS: The
      differences in VEGF expression between males and females (P = 0.43) and different
      ages (P = 0.88) were not significant. The differences in Ki-67 expression was
      between males and females (P = 0.67) and different ages (P = 0.88) were also not
      significant. A positive correlation of VEGF and Ki-67 expression was observed in
      males and females in addi-tion to <= 60 years age group (r = 0.22, r = 0.008, and
      r = 0.58, respectively; P < 0.05). The expression of VEGF had a nega-tive
      relation to Ki-67 in > 60 years group (r = -0.48, P < 0.05). CONCLUSION: The
      expression of VEGF and Ki-67 between males and females and different ages were
      not significant among oral squamous cell carcinoma cases evaluated.

PMID- 22991648
TI  - Dental management of ectodermal dysplasia: two clinical case reports.
AB  - Ectodermal dysplasia is a hereditary disorder associated with abnormal
      development of embryonic ectodermally-derived organs including teeth, nails, hair
      and sweat glands. Hypodontia of the primary and permanent dentition is the most
      com-mon oral finding. Therefore, affected patients need dental prosthetic
      treatments during their developmental years. This re-port presents two cases of
      children affected by ectodermal dysplasia with anodontia. Oral rehabilitation was
      accomplished with removable acrylic prostheses. Treatment had major impacts on
      self-esteem, masticatory function, speech and facial esthetic.

PMID- 22991649
TI  - Infratemporal space infection following maxillary third molar extraction in an
      uncontrolled diabetic patient.
AB  - Infratemporal space infection is a rare but serious sequel of odontogenic
      infection. The diagnosis is difficult due to non spe-cific signs and symptoms.
      Diabetes mellitus as a definitive risk factor for odontogenic infections needs
      more consideration during clinical procedures. We report a case of an undiagnosed
      diabetic patient with isolated infratemporal space infection after tooth
      extraction with presentation of similar signs and symptoms of temporomandibular
      joint and muscle problem.

PMID- 22991650
TI  - New treatments for bacterial keratitis.
AB  - Purpose. To review the newer treatments for bacterial keratitis. Data Sources.
      PubMed literature search up to April 2012. Study Selection. Key words used for
      literature search: "infectious keratitis", "microbial keratitis", "infective
      keratitis", "new treatments for infectious keratitis", "fourth generation
      fluoroquinolones", "moxifloxacin", "gatifloxacin", "collagen cross-linking", and
      "photodynamic therapy". Data Extraction. Over 2400 articles were retrieved. Large
      scale studies or publications at more recent dates were selected. Data Synthesis.
      Broad spectrum antibiotics have been the main stay of treatment for bacterial
      keratitis but with the emergence of bacterial resistance; there is a need for
      newer antimicrobial agents and treatment methods. Fourth-generation
      fluoroquinolones and corneal collagen cross-linking are amongst the new
      treatments. In vitro studies and prospective clinical trials have shown that
      fourth-generation fluoroquinolones are better than the older generation
      fluoroquinolones and are as potent as combined fortified antibiotics against
      common pathogens that cause bacterial keratitis. Collagen cross-linking was shown
      to improve healing of infectious corneal ulcer in treatment-resistant cases or as
      an adjunct to antibiotics treatment. Conclusion. Fourth-generation
      fluoroquinolones are good alternatives to standard treatment of bacterial
      keratitis using combined fortified topical antibiotics. Collagen cross-linking
      may be considered in treatment-resistant infectious keratitis or as an adjunct to
      antibiotics therapy.

PMID- 22991651
TI  - Practical tips for construction of custom Peptide libraries and affinity
      selection by using commercially available phage display cloning systems.
AB  - Phage display technology is undoubtedly a powerful tool for affinity selection of
      target-specific peptide. Commercially available premade phage libraries allow us
      to take screening in the easiest way. On the other hand, construction of a custom
      phage library seems to be inaccessible, because several practical tips are absent
      in instructions. This paper focuses on what should be born in mind for beginners
      using commercially available cloning kits (Ph.D. with type 3 vector and T7Select
      systems for M13 and T7 phage, respectively). In the M13 system, Pro or a basic
      amino acid (especially, Arg) should be avoided at the N-terminus of peptide fused
      to gp3. In both systems, peptides containing odd number(s) of Cys should be
      designed with caution. Also, DNA sequencing of a constructed library before
      biopanning is highly recommended for finding unexpected bias.

PMID- 22991652
TI  - Recent advances in chemical modification of Peptide nucleic acids.
AB  - Peptide nucleic acid (PNA) has become an extremely powerful tool in chemistry and
      biology. Although PNA recognizes single-stranded nucleic acids with exceptionally
      high affinity and sequence selectivity, there is considerable ongoing effort to
      further improve properties of PNA for both fundamental science and practical
      applications. The present paper discusses selected recent studies that improve on
      cellular uptake and binding of PNA to double-stranded DNA and RNA. The focus is
      on chemical modifications of PNA's backbone and heterocyclic nucleobases. The
      paper selects representative recent studies and does not attempt to provide
      comprehensive coverage of the broad and vibrant field of PNA modification.

PMID- 22991653
TI  - Blood pressure and global risk assessment in a Swedish population.
AB  - This study investigated the association between SCORE and the 2007 ESH-ESC blood
      pressure categories and explored achievements of blood pressure goals considering
      global risk. In 2001-2005, a random sample of inhabitants aged 30-74 years in
      southwestern Sweden was invited to a survey of cardiovascular risk factors. The
      study enrolled 2816 participants (participation rate 76%). Blood pressure was
      categorized according to the 2007 ESH-ESC guidelines. Global risk of 10-year CVD
      death was estimated using the Swedish SCORE chart also accounting for additional
      risk from diabetes (SCORE-DM). SCORE-DM increased in both sexes from optimal
      blood pressure to manifest hypertension but did not differ between the normal
      blood pressure categories. However, SCORE-DM became significantly higher among
      those with temporarily high blood pressure (men 3.3 SD (1.7), women 1.1 (1.8))
      and hypertension (3.6 (2.0), 2.0 (2.0)), compared to optimal blood pressure (1.6
      (2.9), 0.6 (1.9)). In the presence of both hypertension and diabetes, high-risk
      subjects dominated (men 76%, women 61%), and correspondingly a major proportion
      of patients with known hypertension were at high risk at a blood pressure
      >=160/100 mm Hg. These findings have strong implications on blood pressure
      evaluation in clinical practice and support the use of SCORE to evaluate global
      risk.

PMID- 22991654
TI  - Pullulanase: role in starch hydrolysis and potential industrial applications.
AB  - The use of pullulanase (EC 3.2.1.41) has recently been the subject of increased
      applications in starch-based industries especially those aimed for glucose
      production. Pullulanase, an important debranching enzyme, has been widely
      utilised to hydrolyse the alpha-1,6 glucosidic linkages in starch, amylopectin,
      pullulan, and related oligosaccharides, which enables a complete and efficient
      conversion of the branched polysaccharides into small fermentable sugars during
      saccharification process. The industrial manufacturing of glucose involves two
      successive enzymatic steps: liquefaction, carried out after gelatinisation by the
      action of alpha-amylase; saccharification, which results in further
      transformation of maltodextrins into glucose. During saccharification process,
      pullulanase has been used to increase the final glucose concentration with
      reduced amount of glucoamylase. Therefore, the reversion reaction that involves
      resynthesis of saccharides from glucose molecules is prevented. To date, five
      groups of pullulanase enzymes have been reported, that is, (i) pullulanase type
      I, (ii) amylopullulanase, (iii) neopullulanase, (iv) isopullulanase, and (v)
      pullulan hydrolase type III. The current paper extensively reviews each category
      of pullulanase, properties of pullulanase, merits of applying pullulanase during
      starch bioprocessing, current genetic engineering works related to pullulanase
      genes, and possible industrial applications of pullulanase.

PMID- 22991655
TI  - Concurrent FDG Avid Nasopharyngeal Lesion and Generalized Lymphadenopathy on PET
      CT Imaging Is Indicative of Lymphoma in Patients with HIV Infection.
AB  - Patients with HIV infection often have generalized lymphadenopathy and/or other
      lymphoid proliferation and are at significantly increased risk for lymphoma. This
      study retrospectively evaluated the diagnostic value of concurrent nasopharyngeal
      lesion and lymphadenopathy on positron emission tomography-computed tomography
      (PET-CT) with fluorine-18 fluorodeoxyglucose (FDG PET-CT) imaging. The eligible
      cases were from patients with HIV infection and lymphadenopathy and referred for
      FDG PET-CT to evaluate lymphoma or other malignancies prior to pathological
      investigation. FDG PET-CT images and interpretation reports were correlated with
      clinical information and pathological diagnoses. Among 22 eligible patients, FDG
      avid nasopharyngeal lesions were incidentally noted in 7 on PET-CT imaging, and
      all had lymphomas diagnosed with subsequent biopsies (6 diffuse large B-cell
      lymphomas and 1 Hodgkin's lymphoma). In the remaining 15 patients with adenopathy
      but no visible nasopharyngeal lesion or uptake on PET-CT imaging, 9 had biopsies
      and lymphomas were diagnosed in 4. The patients with FDG avid retroperitoneal or
      intra-abdominal lymphadenopathy had a greater possibility of lymphoma, compared
      to those with adenopathy localized only in the upper torso. Coexistent FDG avid
      nasopharyngeal lesion and generalized lymphadenoapthy on PET-CT imaging are
      indicative of a malignant lymphoma rather than benign lymphproliferative disease
      or nasopharyngeal carcinoma.

PMID- 22991656
TI  - Meeting the Contraceptive Needs of Key Populations Affected by HIV in Asia: An
      Unfinished Agenda.
AB  - Like all women, women living with and at risk of acquiring HIV have the right to
      determine the number and timing of their pregnancies and to safely achieve their
      reproductive intentions. Yet, many women in Asia affected by HIV lack access to
      family planning services and experience disproportionately high rates of
      unintended pregnancy and abortion. Programs that have succeeded in promoting
      condom use and providing HIV prevention and treatment services in this region
      have largely missed the opportunity to address the contraceptive needs of the key
      populations they serve. The importance of better linkages between family planning
      and HIV policies and programs is now widely recognized by global health
      policymakers and donors. However, to date, most of the efforts to improve these
      linkages have been conducted in Africa. Greater attention is needed to the
      developing, implementing, and evaluating of integrated family planning/HIV
      approaches that are tailored to the political, cultural, and public health
      context in Asia. In this paper, we describe the use of and need for family
      planning among key populations affected by HIV in Asia, discuss the challenges to
      effectively addressing of these needs, and offer recommendations for
      strengthening the linkages between family planning and HIV policies and programs
      in the region.

PMID- 22991657
TI  - Lipoprotein(a): Cellular Effects and Molecular Mechanisms.
AB  - Lipoprotein(a) (Lp(a)) is an independent risk factor for the development of
      cardiovascular disease (CVD). Indeed, individuals with plasma concentrations >20
      mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the
      population. Circulating levels of Lp(a) are remarkably resistant to common lipid
      lowering therapies, and there are currently no robust treatments available for
      reduction of Lp(a) apart from plasma apheresis, which is costly and labour
      intensive. The Lp(a) molecule is composed of two parts, an LDL/apoB-100 core and
      a unique glycoprotein, apolipoprotein(a) (apo(a)), both of which can interact
      with components of the coagulation cascade, inflammatory pathways, and cells of
      the blood vessel wall (smooth muscle cells (SMC) and endothelial cells (EC)).
      Therefore, it is of key importance to determine the molecular pathways by which
      Lp(a) exerts its influence on the vascular system in order to design therapeutics
      to target its cellular effects. This paper will summarise the role of Lp(a) in
      modulating cell behaviour in all aspects of the vascular system including
      platelets, monocytes, SMC, and EC.

PMID- 22991658
TI  - Failed weaning from mechanical ventilation and cardiac dysfunction.
AB  - Failure to transition patient from controlled mechanical ventilation to
      spontaneous breathing trials (SBTs) in a timely fashion is associated with
      significant morbidity and mortality in the intensive care unit. In addition,
      weaning failures are common in patients with limited cardiac reserves. Recent
      advances in cardiac echocardiography and laboratory measurement of serum
      biomarkers to assess hemodynamic response to SBT may provide additional
      information to guide clinicians to predict weaning outcome.

PMID- 22991659
TI  - Effect of Affective Temperaments Assessed by the TEMPS-A on the Relationship
      between Work-Related Stressors and Depressive Symptoms among Workers in Their
      Twenties to Forties in Japan.
AB  - Relatively recently in Japan, immature-type depression, frequently classified in
      the bipolar II spectrum, has increased among workers in their twenties to
      forties. This study explored whether affective temperaments moderate the
      relationship between work-related stressors and depressive symptoms among this
      age group. In July 2004, self-administered questionnaires were distributed to all
      employees of a Japanese company. Eight hundred seventy-four employees (63%)
      returned the questionnaires, with 728 completed. Questionnaires included the 12
      item General Health Questionnaire for assessing depressive symptoms, the
      Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire
      version for assessing affective temperaments, the Effort-Reward Imbalance
      Questionnaire to assess work-related stressors and overcommitment, and questions
      regarding individual attributes and employment characteristics. Multivariate
      logistic regression analysis showed that affective temperaments moderated the
      relationship between work-related stressors and depressive symptoms. Effort (OR =
      1.078), which represents job demands and/or obligations imposed on employees, and
      the upper tertile of overcommitment (OR = 1.589), which represents
      hyperadaptation to the workplace, were risk factors for depressive symptoms.
      Additionally, the results for cyclothymic (OR = 11.404) and anxious temperaments
      (OR = 1.589) suggested that depressive symptoms among this age group may be
      related to immature-type depression.

PMID- 22991660
TI  - Assessing Children's Anxiety Using the Modified Short State-Trait Anxiety
      Inventory and Talking Mats: A Pilot Study.
AB  - Background. Preoperative anxiety complicates treatment and requires assessment by
      nurses in children. Children, with or without disability, are helped when
      pictures are used to support communication. The purpose of this pilot study was
      to test the reliability and validity of the modified short State-Trait Anxiety
      Inventory (STAI) using a modified Talking Mats method in children undergoing day
      surgeries. Method. A modified short STAI with pictorial support along the lines
      of the Talking Mats method was pre- and postoperatively administered to 42
      typically developing children aged three to nine years. The parents assessed the
      children's anxiety, simultaneously and independently, by scoring the short STAI
      by proxy. Results. The modified short STAI showed moderate internal consistency
      and good construct validity in the age group seven to nine years. Conclusions.
      The results of this study support the use of the instrument for self-reports in
      children aged seven to nine years. Future research will explore the possibilities
      of also using this instrument for children with cognitive and communicative
      difficulties.

PMID- 22991661
TI  - Intussusception after laparoscopic gastric bypass surgery: an underrecognized
      complication.
AB  - Introduction. Intussusception after bariatric surgery is an uncommon complication
      that is now being frequently reported. Most people consider dysmotility to be the
      causative mechanism in the absence of obvious etiology. Material and Methods. A
      worldwide search identified literature describing intussusception after bariatric
      surgery. We also included our own patients and analyzed information regarding
      demographic profile, risk factors, presentation, diagnosis, and post treatment
      course. Results. Seventy one patients were identified between 1991 and 2011.
      Majority of the affected patients were females (n = 70, 98.6%); median time to
      presentation after gastric bypass surgery was 36 months. Most patients presented
      with abdominal pain, nausea and vomiting, but without obvious peritonitis. Sixty
      eight patients (96%) required surgery; 48 (70.6%) underwent revision of
      anastomosis, 16 (23.5%) had reduction without resection, while 4 patients (5.9%)
      had plication only. Amongst these, most patients (n = 51, 75%) were found to have
      retrograde intussusception. Post-operatively, 9 patients presented with
      recurrence (range, 0.5-32 months). Five patients, who had earlier been treated
      without resection, eventually required revision of the anastomosis. There was no
      mortality noted. Conclusion. Intussusception after bariatric surgery is uncommon
      and its diagnosis is based on a combination of physicial, radiological and
      operative findings. An early surgical intervention reduces morbidity and prevents
      recurrence.

PMID- 22991662
TI  - Management issues for adolescents with cystic fibrosis.
AB  - The healthy adolescent will encounter major changes in biological and
      psychosocial domains. The adolescent period can be greatly affected by a chronic
      illness. Cystic fibrosis is a terminal illness that can significantly affect an
      adolescent's biological, mental and psychosocial health. This paper discusses
      general issues to consider when managing an adolescent with a chronic medical
      condition, and specifically how cystic fibrosis may impact upon puberty, body
      image, risk-taking behaviours, mental health, independence, nonadherence,
      reproductive health, transition, lung transplantation, and end of life care.

PMID- 22991663
TI  - Radiotherapy for oligometastases and oligo-recurrence of bone in prostate cancer.
AB  - Purpose. To retrospectively evaluate the clinical significance of radiotherapy
      for oligometastases of bone in prostate cancer (PCa). Methods and Materials.
      Between 2003 and 2008, 35 PCa patients with oligometastases of bone were treated
      with radiotherapy. Results. The median radiotherapy dose was 40 Gy. The 3-year
      overall survival rates for all patients, for patients that received a
      radiotherapy dose of >=40 Gy (n = 21) and for those that received <40 Gy (n =
      14), were 77.2%, 90.5%, and 50.0%, respectively. Fourteen out of 16 patients
      (87.5%) who had pain were improved 1 month after radiotherapy. The median
      duration of pain relief was 12 months. Pathological fracture and spinal cord
      compression (SCC) were not seen at the treated sites but developed at
      nonirradiated sites in three patients (8.6%) and in one patient (2.8%),
      respectively. Although the high-dose group (>=40 Gy) achieved better survival
      than the low-dose group (<40 Gy), it was not independent prognostic factor in
      multivariable analysis. Conclusions. Radiotherapy of bone oligometastases in PCa
      was effective for long-term pain relief. Pathological fracture and SCC were not
      seen at the treated sites. A larger clinical trial is warranted to study the
      actual benefit following radiotherapy for oligometastases of bone in PCa.

PMID- 22991664
TI  - Usefulness of whole-body fluorine-18-fluorodeoxyglucose positron emission
      tomography in patients with neurofibromatosis type 1: a systematic review.
AB  - Aim. To systematically review the role of positron emission tomography (PET) with
      fluorine-18-fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1
      (NF1). Methods. A comprehensive literature search of published studies regarding
      FDG-PET and PET/CT in patients with NF1 was performed. No beginning date limit
      and language restriction were used; the search was updated until December 2011.
      Only those studies or subsets in studies including whole-body FDG-PET or PET/CT
      scans performed in patients with NF1 were included. Results. We identified 12
      studies including 352 NF1 patients. Qualitative evaluation was performed in about
      half of the studies and semiquantitative analysis, mainly based on different
      values of SUV cutoff, in the others. Most of the studies evaluated the role of
      FDG-PET for differentiating benign from malignant peripheral nerve sheath tumors
      (MPNSTs). Malignant lesions were detected with a sensitivity ranging between 100%
      and 89%, but with lower specificity, ranging between 100% and 72%. Moreover, FDG
      PET seems to be an important imaging modality for predicting the progression to
      MPNST and the outcome in patients with MPNST. Two studies evaluated the role of
      FDG-PET in pediatric patients with NF1. Conclusions. FDG-PET and PET/CT are
      useful methods to identify malignant change in neurogenic tumors in NF1 and to
      discriminate malignant from benign neurogenic lesions.

PMID- 22991665
TI  - Social activity and cognitive functioning over time: a coordinated analysis of
      four longitudinal studies.
AB  - Social activity is typically viewed as part of an engaged lifestyle that may help
      mitigate the deleterious effects of advanced age on cognitive function. As such,
      social activity has been examined in relation to cognitive abilities later in
      life. However, longitudinal evidence for this hypothesis thus far remains
      inconclusive. The current study sought to clarify the relationship between social
      activity and cognitive function over time using a coordinated data analysis
      approach across four longitudinal studies. A series of multilevel growth models
      with social activity included as a covariate is presented. Four domains of
      cognitive function were assessed: reasoning, memory, fluency, and semantic
      knowledge. Results suggest that baseline social activity is related to some, but
      not all, cognitive functions. Baseline social activity levels failed to predict
      rate of decline in most cognitive abilities. Changes in social activity were not
      consistently associated with cognitive functioning. Our findings do not provide
      consistent evidence that changes in social activity correspond to immediate
      benefits in cognitive functioning, except perhaps for verbal fluency.

PMID- 22991666
TI  - Action-oriented study circles facilitate efforts in nursing homes to "go from
      feeding to serving": conceptual perspectives on knowledge translation and
      workplace learning.
AB  - Background. Action-oriented study circles (AOSC) have been found to improve
      nutrition in 24 nursing homes in Sweden. Little, however, is known about the
      conceptual use of knowledge (changes in staffs' knowledge and behaviours).
      Methods. Qualitative and quantitative methods, structured questionnaires for
      evaluating participants' (working in nursing homes) experiences from study
      circles (n = 592, 71 AOSC) and for comparisons between AOSC participants (n = 74)
      and nonparticipants (n = 115). Finally, a focus group interview was conducted
      with AOSC participants (in total n = 12). Statistical, conventional, and directed
      content analyses were used. Results. Participants experienced a statistically
      significant increase in their knowledge about eating and nutrition, when
      retrospectively comparing before participating and after, as well as in
      comparison to non-participants, and they felt that the management was engaged in
      and took care of ideas regarding food and mealtimes to a significantly greater
      extent than non-participants. The use of AOSC was successful judging from how
      staff members had changed their attitudes and behaviours toward feeding
      residents. Conclusions. AOSC facilitates professional development, better system
      performance, and, as shown in previous studies, better patient outcome. Based on
      a collaborative learning perspective, AOSC manages to integrate evidence,
      context, and facilitation in the efforts to achieve knowledge translation in a
      learning organisation. This study has implications also for other care settings
      implementing AOSC.

PMID- 22991667
TI  - Home-Living Elderly People's Views on Food and Meals.
AB  - Background. The aim of the study was to describe home-living elderly people's
      views on the importance of food and meals. Methods. Semistructured interviews
      with twelve elderly people. The interviews were analysed using qualitative
      content analysis. Results. Respondents described how their past influenced their
      present experiences and views on food and meals. Increased reliance on and need
      of support with food and meals frequently arose in connection with major changes
      in their life situations. Sudden events meant a breaking point with a transition
      from independence to dependence and a need for assistance from relatives and/or
      the community. With the perspective from the past and in the context of
      dependency, respondents described meals during the day, quality of food, buying,
      transporting, cooking, and eating food. Conclusions. Meeting the need for optimal
      nutritional status for older people living at home requires knowledge of
      individual preferences and habits, from both their earlier and current lives. It
      is important to pay attention to risk factors that could compromise an
      individual's ability to independently manage their diet, such as major life
      events and hospitalisation. Individual needs for self-determination and
      involvement should be considered in planning and development efforts for elderly
      people related to food and meals.

PMID- 22991668
TI  - Effects of the intensity of leg isometric training on the vasculature of trained
      and untrained limbs and resting blood pressure in middle-aged men.
AB  - The purpose of this study was to establish whether changes in resting blood
      pressure and the vasculature of trained and untrained limbs are dependent on
      training intensity, following isometric-leg training. Thirty middle-aged males
      undertook an 8 week training programme (4 * 2 min bilateral-leg isometric
      contractions 3 times per week). Two groups trained at either high (HI; 14%MVC) or
      low (LO; 8%MVC) intensity a third group (CON) acted as controls. All parameters
      were measured at baseline, 4-weeks and post-training. Resting SBP (-10.8 +/- 7.9
      mmHg), MAP (-4.7 +/- 6.8 mmHg) and HR (-4.8 +/- 5.9 b.min(-1)) fell significantly
      in the HI group post-training with concomitant significant increases in resting
      femoral mean artery diameter (FMAD; 1.0 +/- 0.4 mm), femoral mean blood velocity
      (FMBV; 0.68 +/- 0.83 cm.s(-1)), resting femoral artery blood flow (FABF; 82.06 +/
      31.92 ml.min(-1)) and resting femoral vascular conductance (FVC, 45%). No
      significant changes occurred in any brachial artery measure nor in any parameters
      measured in the LO or CON groups. These findings show that training-induced
      reductions in resting blood pressure after isometric-leg training in healthy
      middle-aged men are associated with concomitant adaptations in the local
      vasculature, that appear to be dependent on training intensity and take place in
      the later stages of training.

PMID- 22991669
TI  - Therapeutic management of the hallux rigidus.
AB  - Background. Hallux rigidus is a chronic, disabling condition of foot
      characterized by reduced great toe extension. The manual therapy approaches are
      described theoretically however their practical published evidence has not been
      analyzed well. Objective. Aim of the present paper was to systematically review
      the literature available for therapeutic management of the hallux rigidus by
      identifying and evaluating the randomized controlled trials (RCTs) and non-RCTs.
      Methods. To view the hallux rigidus and its rehabilitation, a webbased published
      literature search of Pubmed, Ovid Medline, Science direct, Cochrane Database,
      PEDro database, CINAHL was conducted for last 35 years in August 2010 using 4
      specific keywords "hallux rigidus, physical therapy, chiropractic, and manual
      therapy" typed in exactly same manner in the search column of the databases.
      Result. the review finds that there is acute need of the quality studies and RCTs
      for the manual therapy, chiropractic, or physiotherapeutic management of the
      hallux rigidus. Conclusion. Review conclude that conservative programs for hallux
      rigidus consists of comprehensive intervention program that includes great toe
      mobilization, toe flexor strengthening, sesamoid bones mobilization and long MTP
      joint. The clinician should put an emphasis on the mobilization program with
      proper follow up along with comparative studies for rehabilitation of hallux
      rigidus.

PMID- 22991670
TI  - Management and outcomes of male breast cancer in zaria, Nigeria.
AB  - Male breast cancer is an uncommon disease accounting for only 1% of all breast
      cancers. We present the evaluation, treatment and outcome of male patients seen
      with breast cancer in our institution. Male patients that had histological
      diagnosis of breast cancer from 2001 to 2010 were retrospectively evaluated.
      After evaluation patients were treated with modified radical mastectomy.
      Combination chemotherapy was given to patients with positive axillary lymph
      nodes. Radiotherapy and hormonal therapy were also employed. There were 57 male
      patients with breast cancer which accounted for 9% of all breast cancers seen
      during the study period. Their mean age was 59 +/- 2.3 years. The mean tumor
      diameter was 13 +/- 2.5 cm. Fifty three (93%) patients presented with advanced
      disease including 15 with distant metastasis. Four patients with stage II disease
      were treated with modified radical mastectomy, chemotherapy and tamoxifen. Of the
      30 patients with sage III disease that had modified radical mastectomy, complete
      axillary clearance and tumor free margins were achieved in 25. Overall 21 (36.8%)
      patients were tumor free at one year. Overall 5-year survival was 22.8%. In
      conclusion, male patients with breast cancer present with advanced disease which
      is associated with poor outcome of treatment.

PMID- 22991671
TI  - The Antibacterial Efficacy of Biopure MTAD in Root Canal Contaminated with
      Enterococcus faecalis.
AB  - Aim. The purpose of this in vitro study was to assess the antimicrobial efficacy
      of Biopure MTAD against E. faecalis in contaminated root canals. Materials and
      Methods. Forty-two single rooted extracted human teeth were inoculated with E.
      faecalis and incubated for four weeks. The samples were divided in two control
      and five experimental groups irrigated with 1.5% sodium hypochlorite solution
      (NaOCl); 3% NaOCl; BioPure MTAD; 1.5% NaOCl/17% EDTA; or 3% NaOCl/17% EDTA. After
      a one-week incubation, complete disinfection was confirmed by the absence of
      turbidity in the incubation media. Dentin shavings were taken from samples with
      no turbidity to verify whether E. faecalis was present in dentin tubules. Results
      were analyzed statistically using Fisher's exact test, with the level of
      significance set at P < 0.05. Results. Statistical analysis of the data obtained
      at Day 7 and after dentin shaving analysis showed that BioPure MTAD had
      significantly greater antibacterial activity than 1.5% NaOCl, 1.5% NaOCl/17% EDTA
      and 3% NaOCl/17% EDTA. No significant difference was detected between MTAD and 3%
      NaOCl. Conclusions. These findings suggest that BioPure MTAD possesses superior
      bactericidal activity compared with NaOCl and EDTA against E. faecalis.

PMID- 22991672
TI  - Pattern of Maternal Complications and Low Birth Weight: Associated Risk Factors
      among Highly Endogamous Women.
AB  - Objective. The objective of the study was to examine the pattern of low birth
      weight LBW, maternal complications, and its related factors among Arab women in
      Qatar. Design. This is a prospective hospital-based study. Setting. The study was
      carried out in Women's Hospital, Doha. Subjects and Methods. Pregnant women in
      their third trimester were identified in the log book of Women's Hospital and
      recruited into the study during first week of January 2010 to July 2011. Only
      1674 (out of 2238) Arab women (74.7%) consented to participate in this study.
      Data on clinical and biochemistry parameters were retrieved from medical records.
      Follow-up data on neonatal outcome was obtained from labor room register.
      Results. The incidence of LBW (<2500 g) was 6.7% among Arab women during 2010 in
      Qatar. Distribution of gestational diabetes mellitus (GDM), antepartum hemorrhage
      (APH), maternal anemia, premature rupture of membrane (PROM), maternal
      occupation, parity, sheesha smoking, and parental consanguinity were
      significantly different (P < 0.05) between mothers of LBW and normal birth weight
      NBW (>=2500 g) babies. Multivariable logistic regression analysis revealed that
      previous LBW, consanguinity, parity, smoking shesha, GDM, APH, anemia, PROM,
      maternal occupation, and housing condition were significantly associated with LBW
      adjusting for gestational age. Conclusion. Maternal complications such as GDM,
      APH, anemia, PROM, and smoking shesha during pregnancy are significantly
      increasing the risk of LBW outcome. Screening and prompt treatment for maternal
      complications and health education for smoking cessation during routine antenatal
      visits will help in substantial reduction of LBW outcome.

PMID- 22991673
TI  - In Silico Studies on Fungal Metabolite against Skin Cancer Protein (4,5
      Diarylisoxazole HSP90 Chaperone).
AB  - This work was to find out the dominant secondary metabolites derived from the
      fungus Trichoderma and to test them against skin cancer protein. The metabolites
      were extracted in 80% methanol from the fungal biomass of Trichoderma isolated
      from mangrove sediment. The crude methanol extract was purified and analysed for
      the secondary metabolites by GC-MS. Three predominant compounds (heptadecanoic
      acid, 16 methyl-, methyl ester; 9,12-octadecadienoic acid; cis-9-octadecenoic
      acid) identified in the extracts were screened against the skin cancer protein
      (Hsp90) by in-silico docking method. Of the compounds, heptadecanoic acid, 16
      methyl, methyl ester was the most potent having the docking score of -11.4592
      Kcal/mol. This value was better than the standard drug "dyclonine". This work
      recommends the heptadecanoic acid, 16 methyl, methyl ester for further in vitro
      and in vivo studies towards its development as anticancer drug.

PMID- 22991674
TI  - Effects of Nigerian Piliostigma thonningii Species Leaf Extract on Lipid Profile
      in Wistar Rats.
AB  - Cardiovascular complications and associated conditions remain a major cause of
      death, globally. Piliostigma thonningii has been used for different and several
      medicinal purposes. On this background, the effect of aqueous leaf extract of the
      plant on the lipid profile of physiologically normal rats was examined. Graded
      doses of the extract, 0.0, 0.2, and 0.4 g/kg of body weight (bwt) were orally
      administered to rats for a period of 14 days. The effect of the extract was
      assessed on the basis of comparative determinations of the evaluated indices in
      treated rats vis-a-vis the nontreated group as well as in respect to the
      differences between the basal and final concentrations of the indices in each
      group. The extract, especially at 0.2 g per kg body weight caused a significant
      decrease in the total cholesterol, triglycerides, and low-density lipoprotein
      (LDL) cholesterol in the treated rats when compared to the control group and
      basal concentrations. Though, the level of high-density lipoprotein (HDL)
      cholesterol increased in the treated rats, the increase was not significant when
      compared to the basal concentration. The LDL/HDL ratio in all the experimental
      groups was less than 0.9. The results obtained in this study suggest that P.
      thonningii aqueous leaf extract likely contains antilipidaemic and
      anticholesterolaemic substance(s), which may be useful in the prophylactic and
      curative management of lipid peroxidation, high blood pressure, and
      cardiovascular disorders.

PMID- 22991675
TI  - Rubinstein-taybi syndrome: a case report.
AB  - Rubinstein-Taybi syndrome or Broad Thumb-Hallux syndrome is a genetic disorder
      characterized by facial dysmorphism, growth retardation, and mental deficiency. A
      seven-year-old girl had come to the Department of Pedodontics, Istanbul Medipol
      University, Faculty of Dentistry, Turkey, with a complaint of caries and bleeding
      of gingivae. The patient was mentally retarded. Extraoral features revealed
      distinctive facial appearance with a broad fore head, hypertelorism, broad nasal
      bridge, and beaked nose. Intraoral features observed were talons cusps in the
      upper lateral incisors, carious teeth, and plaque accumulation. Since the patient
      was mentally retarded, the dental treatment was done under GA. The treatment plan
      and dental management of this patient are discussed in this case report.

PMID- 22991676
TI  - Reactive Arthritis due to Shigella Infection after a Visit to Egypt: A Late
      Complication of an Intestinal Infection.
AB  - We describe a case of reactive arthritis following Shigella infection after a
      trip to Egypt. The diagnostic challenge and treatment of this acute medical
      condition are discussed.

PMID- 22991677
TI  - Septic Arthritis of Hip Caused by Salmonella typhi: A Case Report.
AB  - Salmonella typhi usually produces enteric fever and gastroenteritis. The
      infection may spread through blood stream and present as local suppurative
      lesions which may involve any site including the bone and joints. We report a
      case of septic arthritis of hip in a patient with systemic lupus erthematosis.
      The case is presented for its rarity and to highlight the atypical manifestations
      of Salmonella typhi in endemic regions.

PMID- 22991678
TI  - Tethered cord syndrome secondary to the unusual constellation of a split cord
      malformation, lumbar myelomeningocele, and coexisting neurenteric cyst.
AB  - We describe a seminal case report of a child with a tethered cord syndrome
      secondary to the unusual constellation of a split cord malformation, lumbar
      myelomeningocele, and coexisting neurenteric cyst. A 17-year-old adolescent girl
      with a several-month history of myelopathy and urinary incontinence was examined
      whose spinal MRI scan demonstrated a type II split cord malformation with a large
      bone spur and an intradural neurenteric cyst in addition to lumbar
      myelomeningocele. Untethering of the spinal cord was achieved via a lumbar
      laminectomy. Pathological examination confirmed the intradural cyst to be a
      neurenteric cyst. Postoperatively there was stabilization of the neurological
      symptoms. Prophylactic surgery with total resection of the neurenteric cyst when
      feasible and spinal cord un-tethering appears to be associated with excellent
      outcomes.

PMID- 22991679
TI  - Recurrent dacryostenosis as initial presentation of sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease with an unknown etiology. It
      most commonly affects young and middle-aged females. It can affect any organ, but
      mostly lung, skin, and eyes. Up to half of patients are asymptomatic and the
      disease is often detected incidentally on abnormal chest radiography. We report
      the case of a 31-year-old male with bilateral recurrent dacryostenosis. The
      nasolacrimal obstruction was the initial manifestation of systemic sarcoidosis.

PMID- 22991680
TI  - A Diagnostic Dilemma: Waldenstrom's Macroglobulinemia/Plasma Cell Leukemia.
AB  - Waldenstrom's macroglobulinemia is a B-cell neoplasm characterized by
      infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM
      monoclonal gammopathy. It is an uncommon disease with overall incidence of
      approximately 3 per million persons per year, accounting for approximately 1% to
      2% of all hematologic cancers. It has only one-sixth the estimated prevalence of
      plasma cell myeloma. Disease symptoms can be due to infiltration of bone marrow
      and other tissue sites by malignant lymphoplasmacytic cells or due to the effects
      of elevated serum IgM levels. However, patients may present with constitutional
      symptoms only or may be asymptomatic. In our case, patient presented with chief
      complaints of fatigability and dyspnoea and was misdiagnosed as plasma cell
      leukemia on peripheral blood film and bone marrow morphology, but turned out to
      be a case of Waldenstrom's macroglobulinemia on cytoflorometry. The patient was
      referred for chemotherapy but expired on 10th day of admission. The suspected
      cause of death was cardiorespiratory failure.

PMID- 22991681
TI  - Castleman's Disease: A Case Report of the Unicentric Type.
AB  - Castleman's disease, or angiofollicular lymph node hyperplasia, is a relatively
      rare disorder characterized by the benign proliferation of lymphoid tissue
      related to the chronic human herpes virus 8 (HHV-8) infection and the human
      immunodeficiency virus (HIV). Two clinical entities have been described: a
      unicentric presentation with the disease confined to a single anatomic lymph node
      and a multicentric presentation characterized by generalized lymphadenopathy and
      a more aggressive clinical course. Also, three histopathological subtypes have
      been described: hyaline-vascular, plasma cell, and a mixed variant. Preoperative
      diagnosis of hyaline-vascular Castleman's disease is difficult, and the
      definitive result is based on postoperative pathological findings. The gold
      standard therapy is the complete surgical excision.

PMID- 22991682
TI  - Pilonidal Disease Mimicking Fistula-in-Ano in a 15-Year-Old Female.
AB  - Pilonidal disease typically presents with an abscess or intermittent pain and
      drainage in the sacrococcygeal region during the pubertal years. Further
      examination typically reveals pits in the midline of the sacrococcyx area due to
      entrapment of hair with recurrent entrapment, infection, and drainage. The
      following paper describes an unusual presentation of a pilonidal cyst with
      fissure and perianal drainage.

PMID- 22991683
TI  - Ileocecal Intussusception due to a Lipoma in an Adult.
AB  - While intestinal tumors are rare, small intestinal lipomas are even more uncommon
      benign neoplasms. They are usually asymptomatic, but lipomas larger than 2 cm may
      become symptomatic due to obstruction, bleeding, or intussusception. In this
      paper, US and CT findings of a lipoma located in the terminal ileum and causing
      ileocecal intussusception were discussed. We report a case of small bowel lipoma
      that became symptomatic due to intermittent obstruction episodes and ileocecal
      intussuception. If the diagnosis of intestinal lipoma had been made absolutely as
      in our case, they should be removed surgically in elective conditions.

PMID- 22991684
TI  - Adaptive walking in Alzheimer's disease.
AB  - The aim of this study is to analyze dual-task effects on free and adaptive gait
      in Alzheimer's disease (AD) patients. Nineteen elders with AD participated in the
      study. A veteran neuropsychiatrist established the degree of AD in the sample. To
      determine dual-task effects on free and adaptive gait, patients performed five
      trials for each experimental condition: free and adaptive gait with and without a
      dual-task (regressive countdown). Spatial and temporal parameters were collected
      through an optoelectronic tridimensional system. The central stride was analyzed
      in free gait, and the steps immediately before (approaching phase) and during the
      obstacle crossing were analyzed in adaptive gait. Results indicated that AD
      patients walked more slowly during adaptive gait and free gait, using
      conservative strategies when confronted either with an obstacle or a secondary
      task. Furthermore, patients sought for stability to perform the tasks,
      particularly for adaptive gait with dual task, who used anticipatory and online
      adjustments to perform the task. Therefore, the increase of task complexity
      enhances cognitive load and risk of falls for AD patients.

PMID- 22991686
TI  - Stroke in the young 2012.

PMID- 22991688
TI  - Post-collection processing of Schirmer strip-collected human tear fluid impacts
      protein content.
AB  - We examine the impact of post-collection sample handling on the protein
      composition of human tear samples. In particular, we characterize diffusion-based
      protein extraction from Schirmer strips. These strips of filter paper membrane
      are the de facto standard for tear fluid collection and storage, with diffusion
      based protein elution off the strip being the most widely reported protein
      extraction strategy. Nevertheless, the diffusion-based protein elution strategy
      remains uncharacterized regarding downstream functional protein assays. Here, the
      time-dependence, concentration-dependence, and repeatability of the diffusion
      based protein recovery protocol are characterized. Levels of protein
      irrecoverable from the Schirmer strip and lost during sample handling are
      isolated and compared for several major tear proteins. Further, the impact of the
      Schirmer strip and sample handling on the downstream concentration of proteins
      ranging in molecular weight, surface charge, and surface hydropathicity is
      quantified. Diffusion-based protein extraction from Schirmer strips was observed
      to be protein-dependent. Schirmer strips retained tear proteins to varying
      extents: 14.2% of lysozyme, 9.5% of human serum albumin, 27.7% of secretory IgA,
      and 30.9% of mucin 4. Tear protein loss during sample handling ranged from 2%
      (lysozyme) to 41.2% (mucin 4). Strip retention of protein was observed to be
      associated with protein molecular weight and hydrophobic surface area. Greater
      sample handling loss was associated with increased hydrophobic surface area of
      model proteins. Surface charge or surface hydrophilicity was not significantly
      associated with protein loss. We therefore conclude that, although diffusion
      based processing of Schirmer strip-collected tear samples is widely used, these
      protocols may result in total post-collection protein loss which is considerable,
      consistent, and protein-dependent. This loss alters the relative and absolute
      protein concentrations in the sample. A priori prediction of strip-losses for
      individual proteins does not appear to be facile, based on cursory knowledge of
      protein surface properties. Thus, we emphasize "spike and recover" control
      experiments to determine expected elution profiles for target proteins when using
      diffusion-based protein sample preparation for Schirmer strip-collected tear
      fluid.

PMID- 22991689
TI  - Ring opening vs. direct bond scission of the chain in polymeric triazoles under
      the influence of an external force.
AB  - Density functional theory calculations show that both ring opening and chain
      dissociation of polymeric triazoles are facilitated by mechanical stretching of
      the molecules--the latter more than the former. Experimentally observed ring
      opening upon sonication can therefore not be explained by a mechanical stretching
      mechanism alone.

PMID- 22991690
TI  - Exploiting core-shell and core-alloy interfaces for asymmetric growth of
      nanoparticles.
AB  - The alloy phase behavior of nanoparticle (NP) interfaces has been used to tailor
      asymmetric growth. Using either Au-Pd core-shell or Au-Au(x)Pd(1-x) core-alloy NP
      starting materials, the deposition of Ag resulted in asymmetric and symmetric
      growth respectively. The phase segregation of the interface was confirmed by TEM
      and electrocatalytic activity.

PMID- 22991691
TI  - Theoretical studies of reactions of carbon dioxide mediated and catalysed by
      transition metal complexes.
AB  - In this Feature article, we have reviewed theoretical studies of transition-metal
      mediated and catalysed reactions involving carbon dioxide. We have discussed
      fundamental steps related to organometallic reactions of carbon dioxide and
      presented and analyzed reported theoretical studies of transition-metal mediated
      and catalysed reactions of carbon dioxide.

PMID- 22991685
TI  - Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation.
AB  - Although the exact mechanism through which NADPH oxidases (Nox's) generate
      reactive oxygen species (ROS) is still not completely understood, it is widely
      considered that ROS accumulation is the cause of oxidative stress in endothelial
      cells. Increasing pieces of evidence strongly indicate the role for ROS in
      endothelial inflammation and dysfunction and subsequent development of
      atherosclerotic plaques, which are causes of various pathological cardiac events.
      An overview for a causative relationship between ROS and endothelial inflammation
      will be provided in this review. Particularly, a crucial role for specific
      protein SUMOylation in endothelial inflammation will be presented. Given that
      SUMOylation of specific proteins leads to increased endothelial inflammation,
      targeting specific SUMOylated proteins may be an elegant, effective strategy to
      control inflammation. In addition, the involvement of ROS production in
      increasing the risk of recurrent coronary events in a sub-group of non-diabetic,
      post-infarction patients with elevated levels of HDL-cholesterol will be
      presented with the emphasis that elevated HDL-cholesterol under certain
      inflammatory conditions can lead to increased incidence of cardiovascular events.

PMID- 22991687
TI  - On-farm mitigation of transmission of tuberculosis from white-tailed deer to
      cattle: literature review and recommendations.
AB  - The Animal Industry Division of the Michigan Department of Agriculture and Rural
      Development (MDARD) has been challenged with assisting farmers with modifying
      farm practices to reduce potential for exposure to Mycobacterium bovis from
      wildlife to cattle. The MDARD recommendations for on-farm risk mitigation
      practices were developed from experiences in the US, UK and Ireland and a review
      of the scientific literature. The objectives of our study were to review the
      present state of knowledge on M. bovis excretion, transmission, and survival in
      the environment and the interactions of wildlife and cattle with the intention of
      determining if the current recommendations by MDARD on farm practices are
      adequate and to identify additional changes to farm practices that may help to
      mitigate the risk of transmission. This review will provide agencies with a
      comprehensive summary of the scientific literature on mitigation of disease
      transmission between wildlife and cattle and to identify lacunae in published
      research.

PMID- 22991692
TI  - Copper-mediated oxidative direct C-C (hetero)aromatic cross-coupling.
AB  - Some new types of copper-mediated intermolecular oxidative direct C-C
      (hetero)aromatic cross-couplings are described. A combination of the simple
      CuCl(2) salt and molecular oxygen allows 1,3-azoles to couple with terminal
      alkynes directly to form the corresponding heteroarylacetylenes. This direct
      version of Sonogashira-type coupling can be applied to the reaction with
      polyfluoroarenes. A copper acetate complex enables direct biaryl coupling between
      2-arylazines and 1,3-azoles even in the absence of any palladium catalysts.
      Moreover, the Cu-based protocol can be extended to the coupling with indoles and
      pyrroles, in which a catalytic variant is also possible by using an ideal co
      oxidant, atmospheric oxygen. On the other hand, a copper-promoted annulative
      direct coupling of o-alkynylphenols and -anilines with 1,3-azoles can provide a
      unique dehydrogenative approach to C3-azolylbenzoheteroles from nonhalogenated
      and nonmetalated starting materials. In addition, a related N-azolylindole
      synthesis from similar substrates is also disclosed.

PMID- 22991693
TI  - Pd(OAc)2 catalyzed direct arylation of electron-deficient arenes without ligands
      or with monoprotected amino acid assistance.
AB  - An efficient arylation of electron-poor arenes has been developed without the
      addition of external ligands or in the presence of a catalytic monoprotected
      amino acid which assisted the reaction to proceed under mild conditions. The meta
      selectivity was observed under both conditions.

PMID- 22991694
TI  - Mesoporous cross-linked polymer copolymerized with chiral BINAP ligand
      coordinated to a ruthenium species as an efficient heterogeneous catalyst for
      asymmetric hydrogenation.
AB  - We report here a successful preparation of a heterogeneous chiral catalyst from
      copolymerization of mesoporous cross-linked polymer with chiral BINAP ligands,
      followed by coordination of the BINAP with a ruthenium species, which exhibits
      high activity, excellent enantioselectivity, and extraordinary recyclability in
      asymmetric hydrogenation.

PMID- 22991695
TI  - Rapid determination and comparative pharmacokinetics of tetrahydropalmatine in
      spontaneously hypertensive rats and normotensive rats.
AB  - A rapid high-performance liquid chromatographic method was developed and
      validated for determination of tetrahydropalmatine (THP), an active component of
      Rhizoma Corydalis, in rat plasma. The samples were prepared using protein
      precipitation and separated on an Agilent XDB-C(18) column (150 * 4.6 mm, 5 um)
      with the mobile phase consisting of methanol-0.1% phosphate acid solution,
      adjusted with triethylamine to pH 5.5 (65:35). Good linearity was found within
      0.10-10.00 ug/mL of THP in rat plasma sample. The intra- and inter-day precision
      values were less than 10%. The developed method was successfully applied to
      assess the pharmacokinetics of THP in spontaneously hypertensive rats (SHR) and
      normotensive rats. After oral administration of a single dose of THP (60 mg/kg),
      the maximum plasma concentrations were 6.15 +/- 2.1 and 7.54 +/- 2.9 ug/mL for
      normotensive rats and SHR, respectively. The mean values of AUC(0-infinity) of
      THP in SHR were 81.44 +/- 45.0 ug h/mL, significantly higher (p < 0.05) than in
      normotensive rats (44.06 +/- 19.6 ug h/mL). The t(1/2) and MRT in SHR were much
      longer than that in healthy Sprague-Dawley rats, indicating slow elimination of
      THP in SHR. The results indicated that there are some differences in
      pharmacokinetics of THP in SHR and Sprague-Dawley rats and it is very important
      to investigate the pharmacokinetic properties of drugs in pathological
      conditions.

PMID- 22991696
TI  - Integrated phase III trials of bepotastine besilate ophthalmic solution 1.5% for
      ocular itching associated with allergic conjunctivitis.
AB  - Allergic conjunctivitis is a clinical reaction to environmental allergens and is
      manifested by ocular itching caused by IgE-induced mast cell degranulation.
      Bepotastine besilate is a selective H(1)-antagonist with mast cell stabilizing
      properties. This report examines the reduction of ocular itching integrated from
      two conjunctival allergen challenge (CAC) clinical trials comparing bepotastine
      besilate ophthalmic solution (BBOS) 1.5% to placebo in subjects with a history of
      allergic conjunctivitis. Two phase III, double-masked, placebo-controlled,
      parallel-group, CAC clinical trials evaluated BBOS 1.5% versus placebo to reduce
      ocular itching. Eligible subjects were randomly assigned 1:1 to either BBOS 1.5%
      (n = 78) or placebo (n = 79). Ocular itching was graded by subjects using a
      standardized scale (0-4 U). Adverse events and ophthalmic clinical findings were
      recorded for safety. BBOS 1.5% was superior to placebo for reducing CAC-induced
      ocular itching (p < 0.0001) as early as 3 minutes post-CAC and for at least 8
      hours after dosing. Post hoc analyses examining several populations also showed a
      significant improvement (p < 0.0001) for subjects with more severe itching
      response at screening and for the proportion of subjects with complete or nearly
      complete resolution of CAC-induced itching, both outcomes supporting the clinical
      benefit of BBOS 1.5%. Adverse events were generally transient and mild. BBOS 1.5%
      is safe and effective in the treatment of ocular itching associated with allergic
      conjunctivitis within 3 minutes of a CAC and with a sustained duration of action
      of at least 8 hours. (ClinicalTrials.gov numbers: NCT00424398 and NCT00586664).

PMID- 22991697
TI  - Cause-specific mortality in diabetes: recent changes in trend mortality.
AB  - Diabetes is one of the most chronic diseases in Western populations. Mortality
      rates in diabetic patients are higher than in the general population and their
      prognosis following any cardiovascular event is generally worse. Type 1 diabetic
      patients' acute complications-related mortality decreases with time and the
      interval free from the diagnosis of diabetes until the development of chronic
      complications is larger although global mortality is still higher than that of
      sex- and age matched healthy individuals. As a consequence of better primary and
      secondary prevention, recent data in the general population show that there is a
      trend towards decreased cardiovascular events and increased life expectancy. The
      same thing applies for type 2 diabetic patients. However, increased survival in
      the general population associated to epidemic bursts of obesity and sedentary
      lifestyle all over the globe, leads to a higher incidence of type 2 diabetes
      worldwide. This counteracts the diminution of diabetes-related mortality that
      would move forward on an ascending slope in the next decades.

PMID- 22991698
TI  - Reflections: neurology and the humanities. Cerebellum.

PMID- 22991699
TI  - The first International Congress of Road Safety in Mashhad, Iran.

PMID- 22991700
TI  - Clinical experience with gene therapy and bispecific antibodies for T cell-based
      therapy of cancer.
AB  - Unlike any other cell type, T cells have a unique potential to eliminate cancer
      cells and to eventually cure cancer patients. As a result, researchers have made
      extensive efforts over the past three decades to develop therapeutics with the
      potential to mount T cell responses against cancer cells. One way in which such T
      cell responses can be triggered is by vaccines and adjuvants, potentially leading
      to tumor-specific T cell clones and lasting immunity. Alternatively, they can be
      induced with the help of recombinant proteins that either are expressed in
      patients' T cells by gene therapeutic means, or are delivered to patients as
      pharmaceuticals for temporary engagement of T cells. With both recombinant
      technologies, cytotoxic T cells can be engaged for cancer cell lysis regardless
      of T cell receptor specificity and with the prospect of bypassing both complex T
      cell regulation and frequent immune escape mechanisms of tumor cells. In this
      review, we will focus on recombinant approaches for T cell engagement that
      currently are in clinical development. Approaches transfecting patient T cells
      with genes encoding recombinant T cell receptors or antibody fusion proteins will
      be compared to those temporarily engaging T cells by infused recombinant
      bispecific proteins. Initial experience has recently been gained in the clinic
      with both technologies such that their fundamental differences can now be
      discussed on the basis of patient data.

PMID- 22991701
TI  - [Primary lymphoma of the renal sinus].

PMID- 22991702
TI  - Dementia incidence in less-developed countries could be double that of previous
      estimates.

PMID- 22991703
TI  - Alcohol intake in the elderly affects risk of cognitive decline and dementia.

PMID- 22991704
TI  - NIH-funded research provides new clues on how ApoE4 affects Alzheimer's risk.

PMID- 22991705
TI  - Researchers gain better understanding of mechanism behind tau spreading in the
      brain and the progression of Alzheimer's disease.

PMID- 22991706
TI  - Eating more berries may reduce cognitive decline in the elderly: flavonoid-rich
      blueberries and strawberries offer most benefit.

PMID- 22991707
TI  - [Analysis on antibiotic resistance of 1030 Helicobacter pylori strains isolated
      in hospital in Taizhou area, Zhejiang province].

PMID- 22991708
TI  - [Analysis of monitoring results for Vibrio cholerae in Wuzhou city from 2009 to
      2010].

PMID- 22991709
TI  - [Isolation and E gene evolutional analysis of new emerged type 4 dengue virus
      from the outbreak of Guangzhou in 2010].

PMID- 22991710
TI  - [Analysis on the spatial distribution of severe hand-foot-mouth disease cases in
      Lushan county Henan province].

PMID- 22991711
TI  - [Matching study on antibody response between preterm and full-term infants after
      primary immunization and revaccination of hepatitis B].

PMID- 22991712
TI  - [Molecular epidemiological study on the human bocavirus with respiratory tract
      infection in Guangzhou].

PMID- 22991713
TI  - [Analysis of the epidemiological characteristics of hepatitis E and genotypes of
      hepatitis E virus among drug users].

PMID- 22991714
TI  - [A case-control study on the risk factors of gastric cancer in Heilongjiang
      province].

PMID- 22991715
TI  - [Preliminary study on proteome of Yersinia pestis isolated from Yunnan, China].

PMID- 22991716
TI  - [A survey of infection with Angiostrongylus cantonensis around Erhai Lake in
      Dali, Yunnan province].

PMID- 22991717
TI  - [Analysis on neonatal birth weight in Tianjin of China, 2009].

PMID- 22991718
TI  - [Analysis on maternal mortality from ectopic pregnancy during the last ten years
      in Beijing].

PMID- 22991719
TI  - [Molecular typing of Neisseria meningitidis serogroup B strains in Hubei
      province].

PMID- 22991720
TI  - [Study on the epidemiological characteristics of rotavirus and norovirus diarrhea
      in Tianjin].

PMID- 22991721
TI  - ICD 10: time to get serious.

PMID- 22991722
TI  - An answer to the ICD-10 coder productivity fears?

PMID- 22991723
TI  - Stop migraines before they start. Take advantage of proven therapies.

PMID- 22991724
TI  - Ask the doctor.  If you exercise daily (and sweat), can you have more than the
      daily recommended limit of sodium?

PMID- 22991725
TI  - Ask the doctor.  I have been taking an SSRI (paroxetine HCI) for many years for
      chronic anxiety and, at times, panic attacks.  What are the side effects of the
      long-term use of SSRIs?

PMID- 22991726
TI  - Preserving brain function. Living with purpose may protect against changes.

PMID- 22991727
TI  - Heart health and antibiotics safety: Z-Pak update.

PMID- 22991728
TI  - Drop pounds to relieve back pain. Strengthening your core muscles can also help.

PMID- 22991729
TI  - Do you really need that diet soda?  Research connects the drinks to higher heart
      risks.

PMID- 22991730
TI  - Men: pay attention to osteoporosis.  One in four older men suffers a fracture.

PMID- 22991731
TI  - Breast cancer risk and alcohol.  Research suggests no more than one drink per
      day.

PMID- 22991732
TI  - Omega-3 for your eyes.  Research finds DHA may help preserve your vision.

PMID- 22991733
TI  - Psoriasis and vitamin D deficiency. A topical supplement may help your treatment.

PMID- 22991734
TI  - What you should know about: staying on your meds.

PMID- 22991735
TI  - Stop sitting, get moving, to lower diabetes risk.

PMID- 22991736
TI  - Be careful mixing OTC medications with prescription drugs.

PMID- 22991737
TI  - Extra vitamin D may keep you mobile in later years.

PMID- 22991738
TI  - Study finds bananas a good energy source for exercisers.

PMID- 22991739
TI  - Osmoregulation in Azospirillum brasilense: glycine betaine transport enhances
      growth and nitrogen fixation under salt stress.
AB  - Addition of glycine betaine (1 mM) stimulated aerobic growth of Azospirillum
      brasilense Sp 7 in the presence of 0.3 M-NaC1. The nitrogenase activity of whole
      cells was particularly sensitive to salt stress, being almost totally inhibited
      in the presence of the same concentration of salt. Added glycine betaine strongly
      enhanced nitrogen fixation activity under salt stress. Under such conditions,
      maximal nitrogenase activity was obtained at a p(02),value (1 kPa) that inhibits
      nitrogen fixation activity in the absence of salt. We demonstrated the presence
      of a high affinity transport system for glycine betaine, with an apparent K(m),
      of 10 MUM. The osmolarity of the medium regulated the activity of the transport
      system. The maximal transport rates were 4 and 20 nmol min(-l) (mg protein)(-l)
      in cells grown in low-salt and high-salt medium, respectively. A high
      intracellular concentration of glycine betaine (480 mM) was observed only at a
      high osmolarity (0.3 M-NaC1). Glycine betaine uptake was significantly reduced in
      osmotically shocked cells and a glycine betaine binding activity was detected in
      the crude periplasmic shock fluid. This suggests a transport mechanism involving
      a periplasmic glycine betaine binding protein. A. brasilense was unable to use
      the transported glycine betaine as a carbon- or nitrogen-source, in low- or high
      salt medium. Intracellular glycine betaine was not catabolized.

PMID- 22991740
TI  - A bucking-bull veterinarian in the making.

PMID- 22991741
TI  - Retailers tell suppliers to end sow stall use: gestation stalls are focus of
      welfare argument.

PMID- 22991742
TI  - AVMA, AAEP call for ban on soring devices, methods: veterinary organizations hope
      USDA takes action.

PMID- 22991743
TI  - FMD vaccine first allowed to be made in U.S.

PMID- 22991744
TI  - K-State's strategic plan guides progress: FARAD's co-founder will lead new
      computational medicine institute.

PMID- 22991745
TI  - Implications of Controlled Substances Act for mobile veterinary practice.

PMID- 22991746
TI  - Implications of Controlled Substances Act for mobile veterinary practice.

PMID- 22991747
TI  - Implications of Controlled Substances Act for mobile veterinary practice.

PMID- 22991748
TI  - [The objectives of dispensarization in health care of pregnant women].
AB  - The article discusses the conditions and directions of development of
      dispensarization in health care of pregnant women. The study was organized in
      Moscow oblast during 2000-2010. The issues of dispensarization of pregnant women
      are considered based on the primary data from official documents, statistical
      reports (from 32), sociological surveys of obstetricians, gynecologists and
      female patients. The study approved actuality of activities targeted on detecting
      risk factors among reproductively active groups of population where occurs in
      dynamics the accumulation of risks of premature death and negative aspects of
      birth rate. The results of survey of obstetricians, gynecologists and pregnant
      women revealed that the issues of dispenser monitoring of pregnant woman need an
      ultimate attention to enhance health of women and children as an important
      reserve for the future of Russia.

PMID- 22991749
TI  - [On the tendencies of cardiologic morbidity and mortality in Tverskaya oblast].
AB  - The article demonstrates that the cardiologic morbidity and mortality in
      Tverskava oblast is quite low, taking into account a significant portion of older
      population and high mortality rate of corresponding nosology among total and able
      bodied population. This contrasting data is analyzed against the background of
      average trends in the Russian Federation, the central federal okrug, Voronejskaya
      and Tambovskaya oblasts similar to Tverskaya oblast in intensity of processes of
      aging but much less urbanized.

PMID- 22991750
TI  - [The information technologic aspects of smart monitoring setting up].
AB  - The setting up of smart monitoring system is an actual issue in conditions of
      development of informational infrastructure of public health. This approach
      provides an opportunity concerning both data gathering and its analysis followed
      by development of management recommendations.

PMID- 22991751
TI  - [The impact of ecologic risk factors in mining cities of South Ural].
AB  - The analysis of common and primary morbidity according the statistic form 12 is
      presented. The assessment of health risk in major age groups of population in
      mining cities of Republic of Bashkortostan is provided. The dynamics of morbidity
      indicators trends to increasing because in all age groups higher levels of
      morbidity were detected. The analysis of input of environment pollution into
      morbidity of population of cities of Utchaly and Sybay revealed that a
      significant role is played by environment factors. So, the existence of specific
      geochemical territory and anthropogenic pollution of environment with inorganic
      compounds of highly toxic metals is a most significant risk fasctor impacting
      population health. This condition urges to develop various preventive measures.

PMID- 22991752
TI  - [On the demographic aspects of regional programs of health system modernization].
AB  - The regional programs health system modernization is to be based on monitoring
      population health and needs in medical care. The analysis and forecasting of
      demographic trends in the region is one of important components of such analysis.
      At that, a special attention is paid to the issues related to birth rate,
      mortality and aging of population.

PMID- 22991753
TI  - [The structural functional analysis of functioning of day-hospitals of the
      Russian Federation].
AB  - The article deals with the results of structural functional analysis of
      functioning of day-hospitals in the Russian Federation. The dynamic analysis is
      presented concerning day-hospitals' network, capacity; financial support, beds
      stock structure, treated patients structure, volumes of diagnostic tests and
      curative procedures. The need in developing of population medical care in
      conditions of day-hospitals is demonstrated.

PMID- 22991754
TI  - [The characteristics of organization of ambulatory polyclinic medical care of
      patients of different social status in the Republic of Dagestan].
AB  - The article analyses the issues of different of quality of medical care between
      urban and rural population in the Republic of Dagestan. The technique of
      sociologic survey was applied. The comparative analysis was applied for
      summarizing of different responses from respondents dwelling in urban, plain and
      mountain areas. The following positions are considered: material sufficiency,
      pharmaceutical support, medical care demand in polyclinic. The differences are
      established depending on place of birth and primary causes. The enlarged inter
      sectoral approach is proposed to organize effective medical care in the Republic
      of Dagestan.

PMID- 22991755
TI  - [The development of organization of medical care to patients with degenerative
      dystrophic diseases of lumbosacral section of spine].
AB  - The article deals with issues of development of organizational technologies in
      the field of medical care of patients with degenerative dystrophic diseases of
      lumbosacral section of spine. The comprehensive evaluation of the process of
      medical care provision to this category of patients revealed the need in measures
      concerning the reconstruction and development of effectiveness of process. The
      model is elaborated concerning medical cary of patients with backache with the
      purpose to establish the succession between various stages of medical care
      provision. The issues of rational distribution of manpower resources and
      exclusion of duplication of activities on different stages of the process are
      considered.

PMID- 22991756
TI  - [The organization and quality of specialized hospital care of early age
      children].
AB  - The article considers the quality of specialized hospital care of early age
      children based on the materials of 568 records of hospital patients in the
      Republican children hospital of Makhachkala. The important imperfections are
      detected. About 30% of patients suffered from untimely and insufficient
      treatment. The untimely consultations took place in case of 15.6% of patients.
      About 22% of patients didn't receive a whole course of treatment needed. The
      comprehensive treatment of children was not applied in fullness at the discharge
      from the hospital in 14% of patients. The guidelines to enhance the quality of
      specialized hospital care of early age children are developed.

PMID- 22991757
TI  - [The analysis of functioning of general practitioners offices in rural area].
AB  - The article deals with the analysis of functioning of general practitioners
      offices in rural municipal districts of Penzenskaya oblast. The particular forms
      of such practices (only adults, adults and children) are analyzed. The analysis
      of functional capacity of general practitioners offices depending on size of
      population assigned to the feldsher posts is presented. The measurement of work
      of general practitioner in pilot rural municipal district is carried out. The
      need in general practitioners offices and planned size of both adult and children
      population per one position of general practitioner is substantiated. The
      recommendations concerning the estimate of numbers of positions of general
      practitioners depending on size of population assigned to the feldsher posts are
      given.

PMID- 22991758
TI  - [The main directions of reorganization of functioning of emergency care station
      of Blagoveschinsk].
AB  - The implementation of modern medical information statistical system "MISS-03" on
      the emergency care station of Blagoveschinsk resulted in shortening of call
      feedback time and supporting the overall process of calls processing (from
      dispatcher call reception to statistical data processing). The application of
      thrombolytic therapy in case of acute myocardium infarction resulted in mortality
      decrease at pre-hospital stage, more benevolent course of disease and decrease of
      hospital lethality.

PMID- 22991759
TI  - [The sociologic survey of oncologic patients for the purpose to identify the
      treatment process problems].
AB  - The results of survey confirmed that one of systemic components of medical care
      of patients with oncologic diseases is the organization of conditions for
      psychological support.

PMID- 22991760
TI  - [The public health reforms of regional level in Canada].
AB  - The article analyses the issues of organization and implementation of reforms of
      health system in globalization conditions. The directions of globalization impact
      on medical health care of population are demonstrated on the example of Canada.
      It is emphasized that the states can preserve the capacity to actively operate in
      conditions of the new international line-up of forces and properly respond to the
      needs in health of national population. The main condition is to determine
      purposes putted in to health care system by medicine commercialization, medical
      sanitary care (support, security) and health management. The alterations of
      mechanisms of legal regulation of public health system of Canada are analyzed in
      details.

PMID- 22991761
TI  - [From the actual foreign experience in organization of functioning of day
      hospital for children].
AB  - The article deals with the issues of organization of functioning of day-hospital
      for children in particular foreign countries. The hospitals and medical centers
      of USA and Canada exemplify the positive experience of curative, rehabilitative
      and psychological care to children in daytime. The demand for effective medical
      service of this type by children and their parents is noted. The possibility of
      using this experience in Russian health care is discussed.

PMID- 22991762
TI  - [The practical medicine and its reformation in XVII-XIX centuries, report 2: the
      becoming of clinical medicine].
AB  - The article deals with the becoming of clinical medicine in chronologic scope
      from 1800 to middle 1870s. The major scientific achievements related to the
      application of practical medicine such methods as clinical anatomical comparison,
      laboratory experiment, chemical analysis, physical, instrumental, functional,
      laboratory diagnostics are discussed.

PMID- 22991763
TI  - [The ideas of M.V. Lomonosov: the characteristics of population health and
      medical care of Pomorye in XVIII-XIX centuries].
AB  - The article considers the indicators of population health of Archangelskaya
      gubernia in second half of XVIII-XIX centuries: population size, gender
      structure, birth rate and mortality structure, including infant and children. The
      cultural traditions of Pomorye in XVIII-XIX centuries are analyzed. The main
      characteristics of conditions and structure of health system of this time are
      given.

PMID- 22991764
TI  - [The first Pasteur stations in Russia].
AB  - The article considers the initial stage of organization of antirabic care of
      population of Russia. The history of organization in 1886 of the five initial
      Pasteur stations in Russia is presented The main directions of stations
      functioning and assessment of their activities is given.

PMID- 22991765
TI  - [To the 120 anniversary of S.S. Yudin].
AB  - The article characterizes the many-sided activity of prominent surgeon S.S.
      Yudin. For the first time the unknown memoirs evidences of contemporaries of the
      scientist. The new interpretation and comprehension is given to particular facts
      of the surgeon's biography.

PMID- 22991766
TI  - [The Moscow Scientific Society of Historians of Medicine in 2011].

PMID- 22991767
TI  - [The reliability and validity of a new scale for measuring the concept of Ikigai
      (Ikigai-9)].

PMID- 22991768
TI  - [A survey examining the countermeasures taken by restaurants to prevent passive
      smoking and an analysis of the economic impact of smoking prohibition in
      restaurants].
AB  - OBJECTIVES: This study examines the countermeasures taken by restaurants to
      prevent passive smoking and the impact of smoking prohibition on both the number
      of customers and sales volume in restaurants. METHODS: An interview-based survey
      was administered to 8,558 restaurant managers in Aichi prefecture. The survey
      questions concerned the countermeasures taken against passive smoking within each
      restaurant and the effect of the prohibition of smoking on both the number of
      customers and sales volume between November 1, 2009, and February 26, 2010.
      RESULTS: Seven thousand and eighty managers responded to the survey (response
      rate 83%). The proportion of managers of restaurants with a complete smoking ban
      was 16.4%, of restaurants with a smoking and non-smoking room or section was
      20.2%, and of restaurants where no countermeasures were taken was 63.4%. The
      results showed that among the restaurants with a complete smoking ban, the number
      of customers and sales volume increased in 1.5%, decreased in 3.9%, and did not
      change in 95%. Differences in countermeasures were seen according to the type of
      restaurant. A high proportion of restaurants with a complete ban were curry shops
      and fast food restaurants, while few such restaurants were bars or Izakaya
      (Japanese style bars) and Yakiniku (Korean style BBQ) restaurants. CONCLUSION:
      The results of this large-scale survey in Aichi prefecture suggest that the
      economic impact of smoking prohibition in restaurants, in terms of the number of
      customers and sales volume, is small.

PMID- 22991769
TI  - [Cigarette smoking and lifestyle-related diseases in Japan. A longitudinal study
      of health check-up data from urban areas].

PMID- 22991771
TI  - [Medical care costs and the characteristics of higher medical costs among BMI
      groups in the early-stage elderly analysis of data obtained from a large-scale
      study of 29,490 elderly].

PMID- 22991770
TI  - [Professional confidence of public health nurses and related factors].
AB  - OBJECTIVES: The present study attempts to clarify the level of professional
      confidence of public health nurses and to identify the factors that may influence
      this confidence. METHODS: An anonymous, self-administered, voluntary, paper-based
      questionnaire was distributed to 328 public health nurses working full-time
      within prefectures and municipalities. Professional categorization was conducted
      by referencing the relevant literature and a factor analysis was performed to
      investigate construct validity and reliability coefficients. The factors
      considered influential to participant's confidence were classified as "individual
      factors", "workplace factors", and "educational factors within the current
      education system". The relationship between these factors and participants'
      professional confidence was then analyzed. RESULTS: In total, we received 203
      responses (61.9%) by mail. Of these, 117 (35.7%) were valid. The mean age of
      respondents was 44.1 +/- 9.49 years. On the basis of the number of years of
      experience, they were classified into newly-hired (6.8%), middle management
      position (59.9%), and administrative position (33.3%). Municipal public health
      nurses accounted for 77.8% of the respondents, while 22.2% were prefectural
      public health nurses. The professional components considered to influence
      respondents' confidence were found to consist of 19 items in three major areas:
      (1) management and clerical work according to the position held, (2) individual
      counseling services based on health guidance, and (3) scientific evidence-based
      evaluation. Professional confidence is built on following three factors
      "individual factors" (based on years of service), "workplace factors"
      (affiliations and official title), and "educational factors within the current
      education system" (registration with an academic society or participation in case
      study meetings and project meetings). CONCLUSION: The results suggest that to
      improve their professional confidence, public health nurses require not only an
      accumulation of experience but also improvements in the current education system,
      including training on objective evaluation of individual cases and business
      reviews.

PMID- 22991772
TI  - [The wording of original scientific articles in health].

PMID- 22991773
TI  - [Saline solution as culture media from a viewpoint of nosocomial bacteremia].
AB  - INTRODUCTION: Nutrient-containing aqueous solutions for parenteral use are
      susceptible of microbial contamination, beeing an important cause of serious
      infectious complications. Objective. To determine the capacity of organisms for
      growing in saline as compared with dextrose solution and tri-destilled sterile
      water. MATERIAL AND METHODS: Experimental controlled study. Different microbial
      strains were innoculated in aqueous solutions (5% dextrose and 0.9% saline) as
      well as tri-destilled sterile water. Results were analized using the ANOVA test
      for repeated measurements. RESULTS: In 0.9% saline solution, all the
      Enterobacteriaceae strains tested had a significant increase in their bacterial
      quantification in the analized time period (F = 8.35, p = 0.0145). For most
      organisms, the growth was even better than the one observed in nutrient
      containing solution. CONCLUSIONS: The 0.9% saline solution can support
      significative growing of potentially pathogenic bacteria. We recommend a strict
      compliance to the good nursing standards when handling this kind of solutions.

PMID- 22991774
TI  - Efficacy and safety of clarithromycin in pediatric patients with upper
      respiratory infections: a systematic review with meta-analysis.
AB  - PURPOSE: Upper respiratory infections (URIs) are one of the most common
      infectious diseases in children. Macrolides had been considered one of the best
      options of treatment. Instead of clarithromycin is one of the macrolides most
      used, meta-analysis about the safety and efficacy of this drug has not been
      published. MATERIALS AND METHODS: A systematic review with meta-analysis of
      randomized controlled trials (RCTs) was conducted. Studies in subjects < or = 12
      years of age with URIs were included. Central Cochrane Registry, MEDLINE, EMBASE,
      Lilacs and Artemisa from 1966 to January of 2011 were reviewed. Clinical cure,
      clinical success, bacteriological eradication, relapse risk and adverse events
      risks were analyzed. Risks ratios (RR) with 95% confidence intervals (CI 95%)
      were calculated, using a fixed effects model. RESULTS: 24 studies, from a total
      of 76 RCTs were included. Clarithromycin was therapeutically equivalent to other
      antibiotics studied with respect to clinical cure [RR 1.02 (0.98 to 1.06), p NS],
      clinical success [RR 1.01 (0.99 to 1.03), p NS] and relapse risk [RR 1.34 (0.81
      to 2.21), p NS], but was associated with a better bacteriological eradication [RR
      1.06 (1.02 to 1.09), p 0.001], and a lower risk for related adverse events [RR
      0.77 (0.65 to 0.90), p = 0.001]. CONCLUSIONS: High quality evidence showed that
      Clarithromycin is a safe and effective alternative for the treatment of URIs in
      pediatric patients. Is superior to other antibiotics in relation to bacterial
      eradication. Its equivalence profile related to clinical cure, clinical success
      and relapse risk, let to consider it as an important alternative.

PMID- 22991775
TI  - Risk factors associated with retinopathy of prematurity and visual alterations in
      infants with extremely low birth weight.
AB  - OBJECTIVE: Retinopathy of prematurity (RoP) is a retinal vascular disease and a
      frequent cause of blindness in infants. Our objective was to measure the
      frequency of RoP in infants with extremely low birth weight (ELBW, < 1,000 g) at
      the National Institute of Perinatology, Neonatal Intensive Care Unit (NICU),
      weighing the association of RoP with several risk factors and their results, such
      as refractive errors and strabismus. MATERIAL AND METHODS: We carried out two
      cross-sectional observations of our prospective study: one near birth, and the
      second, after a long-term follow-up. Funduscopic examination was performed while
      the infants were in the NICU to detect RoP. Infants with RoP were followed up by
      means of visual examinations during an average 8-year period and results were
      compared with those of infants with ELBW without RoP. RESULTS: Of the 139
      screened infants at the NICU, 24.4% were identified with RoP: 79% of these with
      grade I retinopathy; 18% with grade II, and one infant with grade III
      retinopathy. The zones involved were as follows: zone 1, 12%; zone 2, 79%, and
      zone 3, 9%. The following were associated with retinopathy: eclampsia (p =
      0.003); gestational age (0.01); multiple gestation (0.03); days of stay at NICU
      (< 0.001); mechanical ventilation (0.001); hypoxia (0.01); oxygen therapy (<
      0.001); apnea (0.005); acidosis (0.001), and hypercapnia (0.001). Retinopathy was
      self-limited in all children. We found no differences in frequency of refractive
      errors and strabismus between children with RoP and controls. CONCLUSIONS: We
      observed a moderately high frequency of RoP in infants with ELBW in Mexico City
      and recommended early mandatory screening for early intervention.

PMID- 22991776
TI  - [Evaluation of alignment on knees through a software].
AB  - INTRODUCTION: Diseases of the musculoskeletal system are often accompanied by
      postural deformity or malalignment. Genu varo or genu valgo can be found in the
      knees. It is necessary to have a diagnostic support test for diagnosis as well as
      for follow-up of cases since these diseases are frequently progressive and over
      time have serious repercussions on patient quality of life. Objective. To
      evaluate a software program that processes digitalized photographs as a
      diagnostic test for measuring the mechanical axis in patients with genu varo and
      genu valgo. MATERIALS AND METHODS: The mechanical axis in both knees was measured
      by means of radiography (golden standard) and by means of a software program
      (proposed diagnostic test) in one hundred patients. Mechanical axis was
      considered to be abnormal when the angle was equal to or greater than four
      degrees. Sensitivity, specificity, positive predictive value, and negative
      predictive value were determined. Interobserver variation was evaluated with
      kappa statistics. RESULTS: In relation to right knee genu varo, sensitivity,
      specificity, positive predictive value, and negative predictivie value were 0.84,
      0.87, 0.84, and 0.87, respectively, and for the left knee values were 0.86, 0.87,
      0.84, and 0.89, respectively. For genu valgo in the right knee, sensitivity,
      specificity, positive predictive value, and negative predictive value were 0.78,
      0.98, 0.95, and 0.92, respectively, and in the left knee were 0.88, 0.95, 0.88,
      and 0.95, respectively. Kappa value was 0.9 in the right knee and 0.8 in the left
      knee. CONCLUSION: The software program (diagnostic test) was useful for
      diagnosing genu varo or genu valgo, representing a safe and low-cost study.

PMID- 22991777
TI  - [Effect of a community-based intervention to improve the knowledge on the warning
      signs of maternal complications among Mayan women from Yucatan randomized
      controlled trial].
AB  - OBJECTIVE: To evaluate a community-based intervention aimed to improve women's
      knowledge on alarm signs for preeclampsia-eclampsia, obstetrical hemorrhage, and
      puerperal sepsis, in Mayan pregnant women in the state of Yucatan, Mexico, in
      2008, using participatory methodology. MATERIAL AND METHODS: Community-based
      randomized controlled trial, with experimental (n = 28) and control (n = 28)
      groups. Participatory strategies with translators of Mayan language were used.
      Analysis of differences in differences was carried out to evaluate the effect of
      intervention. RESULTS: The intervention increased knowledge on alarm signs for
      preeclampsia-eclampsia in 42.9% (p = 0.012), obstetrical hemorrhage in 32.1% (p =
      0.071) and puerperal sepsis in 25.0% (p = 0.659). Control group increased 32.1%
      (p = 0.033) knowledge on alarm signs for puerperal sepsis. Overall effect of
      intervention was 33.3% (p = 0.007). CONCLUSIONS: The community-based intervention
      improved overall knowledge of women on alarm signs and specific knowledge on
      alarm signs for preeclampsia-eclampsia. It is necessary to spread this
      methodology, so that a greater number of women of the community will also be
      benefitted with the intervention.

PMID- 22991778
TI  - Changes in peripheral blood mononuclear cells glutamine synthetase mRNA after
      exercise in healthy volunteers: exploring an alternative proposal for non hepatic
      ammonia metabolism.
AB  - BACKGROUND: Glutamine synthetase (GS) plays a central role in the inter-organ
      metabolism of ammonia and hepatic encephalopathy. The main objective of the
      present work was to disclose the possible effect of exercise on GS mRNA
      expression in peripheral blood mononuclear cells (PBMC) within a group of healthy
      volunteers. MATERIAL AND METHODS: PBMC were studied instead of skeletal muscle
      because of ethical concerns. Characterization of GS in lymphocytes was carried
      out by indirect immunofluorescence and Western blot. After a pilot trial,
      expression of GS mRNA in PBMC was assayed by serial measurements in healthy
      volunteers who had exercised on a treadmill, and on a control group who had not.
      Muscle mass was estimated by bioimpedance. RESULTS: Cytoplasmic GS had a
      molecular weight of 44 kDa. Serial measurements of its mRNA demonstrated an
      increase in the treadmill (n = 29), but not in the control group (n = 13) (p <
      0.05). Peak expression occurred at 1 h in males and at 6 h in females. There was
      a positive correlation between muscle mass and the increase of the enzyme mRNA
      after exercise. CONCLUSION: Exercise can increase the expression of GS mRNA in
      PBMC in healthy volunteers. Based on these preliminary results and on well
      established physiological concepts, a hypothesis for non-hepatic ammonia
      metabolism is conceived. In the future could become part of the treatment of low
      grade hepatic encephalopathy.

PMID- 22991779
TI  - [Experimental bacterial contamination of bile and liver in mongrel dogs: an
      alternative treatment with cephalone, a hybrid of cephalosporine
      fluoroquinolone].
AB  - OBJECTIVES: A longitudinal, randomized, single blind study was done to evaluate
      the efficacy of an antibacterial hybrid molecule (beta-lactamic-fluoroquinolone)
      named cephalone after biliary-enteric-bypass (BEB). MATERIAL AND METHODS: Four
      groups of mongrel dogs were operated on three consecutive periods. Cultures of
      bile and liver were obtained and assessed, followed by obliteration of common
      bile duct and BEB to groups A, B and C. Group D served as a control. Ten days
      later the group A received conventional treatment based on ampicillin/gentamicin
      and groups B and C, cephalone in two different concentration schemes during 10
      consecutive days. Further samples were processed for bacteria and additional
      liver biopsies were obtained for histopathological analysis. RESULTS: All three
      treatments reverted bacterial contamination in the liver and most of the bile
      samples were negative or showed a significant decrease in the number of colony
      forming units (p = 0.002). Histopathological analysis proved no lesions.
      CONCLUSIONS: Comparison of efficacy among antibacterial treatments revealed
      undistinguishable efficacy in this short-term assessment of bacterial
      contamination after BEB in dogs. The use of cephalone could be considered as a
      viable treatment or prophylaxis in bacterial infections occurring after BEB.
      Further studies are needed to assess long-term impact of the cephalone in this
      setting.

PMID- 22991780
TI  - [Major neurotransmitters involved in the regulation of sleep-wake cycle].
AB  - Neuronal activity in the central nervous system undergoes a variety of
      electrophysiological changes along the sleep-wake cycle. These changes are
      modulated by a complex interaction between different neurochemical systems
      located throughout the brain. Within brainstem and hypothalamus there are a
      number of neuronal populations that promote wakefulness through the action of
      different neurotransmitters like noradrenaline, serotonin, histamine and orexin.
      These systems act together in the generation and maintenance of wakefulness,
      however although each one contributes in a unique way no neurotransmitter seems
      to be absolutely necessary because wakefulness is not completely inhibited in the
      absence of any of them. On the other hand, neurons located in the hypothalamus
      and brainstem are involved in initiating and maintaining sleep. These neurons
      contain neurotransmitters such as acetylcholine and GABA and have projections to
      nuclei involved in wakefulness regulation. Recently, models have been proposed
      suggesting that sleep is modulated by flip-flop switches which are characterized
      by neuronal circuits with different neurotransmitters and that interacting to
      regulate the initiation and maintenance of the different stages of sleep wake
      cycle. This review is based on pharmacological, electrophysiological and
      neurochemical studies with the aim of analyze the major neurotransmitters and the
      cerebral regions involved in the regulation of wakefulness and different states
      of sleep.

PMID- 22991781
TI  - [Actual aspects of chronic myeloid leukemia].

PMID- 22991782
TI  - [Operative results in cardiovascular surgery of the neonate].
AB  - OBJECTIVE: To present our institutional postoperative results in cardiovascular
      surgery of the neonate, and to give an idea of its contribution to the national
      problematic knowledge in this area. MATERIAL AND METHODS: A retrospective,
      descriptive, and observational study was carried out, including all neonates with
      congenital heart disease who were operated at the Ignacio Chavez National
      Cardiology Institute in a 7 year period. We made special emphasis in
      postoperative morbidity and mortality, as well as in the risk factors for early
      mortality. RESULTS: We operated on 484 neonates with congenital heart disease due
      to total anomalous pulmonary venous conection, classic transposition of great
      arteries, pulmonary atresia, and aortic coarctation. Causes for early mortality
      were cardiac failure, pulmonary hypertension, pulmonary sepsis, and arrhythmias.
      Operative mortality was 12.2% and was due mainly to congenital heart disease with
      5 and 6 RACHS-1 risk score. Risk factors for operative mortality were: age < 15
      days, body surface area < 0.20 m2, weight < 4 kg, and univentricular heart
      physiology. CONCLUSIONS: There is still a high operative mortality for complex
      neonatal heart disease in this series. Our institutional outcomes can not be
      extrapolated to the rest of the country, but highlights several challenges that
      national pediatric health care institutions and associations must assume in order
      to improve the attention that neonatal patients demand.

PMID- 22991783
TI  - [Toxocariasis: evidence of a disease ignored by clinicians and laboratories].

PMID- 22991784
TI  - Patient portals: express lane on the health information highway.

PMID- 22991785
TI  - Treating healthcare with health "I"T.

PMID- 22991786
TI  - Consumer preparedness in the face of disaster.

PMID- 22991787
TI  - Structuring the spoken word.

PMID- 22991788
TI  - Data ownership evolves with technology.

PMID- 22991789
TI  - HIM's expanding role in clinical data analysis and mapping.

PMID- 22991790
TI  - Developing quality measures for longitudinal care.

PMID- 22991791
TI  - Consumer-facing health information practices.

PMID- 22991792
TI  - Coding open fractures in ICD-10-CM.

PMID- 22991793
TI  - Back to the basics of spine surgery.

PMID- 22991794
TI  - Patient engagement important, but definitions vary.

PMID- 22991795
TI  - [New medical training system--specialist training and publication of papers].

PMID- 22991796
TI  - [Long-term effects of pulsed radiofrequency on the dorsal root ganglion and
      segmental nerve roots for lumbosacral radicular pain: a prospective controlled
      randomized trial with nerve root block].
AB  - BACKGROUND: Although pulsed radiofrequency (PRF) method for lumbosacral radicular
      pain (LSRP) is reportedly effective, there are no prospective controlled trials.
      We assessed the long-term efficacy of PRF of the dorsal root ganglion and nerve
      roots for LSRP as compared with nerve root block (RB). METHODS: The study
      included 27 patients suffering from LSRP. The design of this study was randomized
      with a RB control. In the PRF group, the PRF current was applied for 120 seconds
      after RB. In the RB group, the patients received RB only. Visual analogue scale
      (VAS) was assessed immediately before, and immediately, 2 hours, 1 day, 1 week, 1
      month, 3 months, 6 months, and 1 year after the procedure. P<0.05 was regarded as
      denoting statistical significance. RESULTS: In both groups, the VAS not only of
      short-term but also of long-term (6 months and 1 year after procedure)
      significantly decreased as compared with that before treatment (P<0.05). There
      were no significant differences of VAS between the two groups at the same time
      points. CONCLUSIONS: This study indicates that PRF adjacent to the dorsal root
      ganglion and nerve roots for LSRP has long-term effects. There were no
      significant differences of long-term effects between the two groups.

PMID- 22991798
TI  - [Appropriate dose of remifentanil to blunt tracheal intubation stress response in
      patients with severe aortic stenosis].
AB  - BACKGROUND: In anesthetic induction of patients with severe aortic stenosis,
      maintenance of normal heart rate and blood pressure is critical. Remifentanil can
      blunt cardiovascular responses to tracheal intubation, but may cause circulatory
      collapse due to potent vasodilating effect. We studied retrospectively the
      optimal dose of remifentanil, which blunts cardiovascular responses to tracheal
      intubation and provides the hemodynamic stability to patients with severe aortic
      stenosis. METHODS: We administerd remifentanil with three different doses (0.3
      microg x kg(-1) x min(-1) : n=4, 0.5 microg x kg(-1) x min(-1): n=7, 1 microg x
      kg(-1) x min(-1): n=7) in anesthetic induction of patients with aortic stenosis.
      Systolic arterial blood pressure and heart rate before and after the tracheal
      intubation were recorded. The degree of change of post to pre-intubation of
      systolic arterial pressure and heart rate was calculated and compared among
      groups. RESULTS: There were no significant differences in background among the
      groups. The ratio between before and after tracheal intubation of systolic
      arterial pressure was significantly lower in the group of 0.5 microg x kg(-1) x
      min(-1) and 1 microg x kg(-1) x min(-1). There was no significant hypotension or
      bradycardia which may lead to severe cardiovascular depression. CONCLUSIONS: We
      found that more than 0.5 microg x kg(-1) x min(-1) of remifentanil can blunt
      cardiovascular responses to tracheal intubation without severe cardiovascular
      depression.

PMID- 22991797
TI  - [Effects of propofol and ketamine on postoperative hepatic and renal function:
      comparison between fentanyl and remifentanil as an adjuvant].
AB  - BACKGROUND: The aim of this study was to assess the effects of two different
      opioids, fentanyl and remifentanil, as an adjuvant in propofol-ketamine based
      total intravenous anesthesia (PFK and PRK) on post-anesthetic hepatic and renal
      function. METHODS: We conducted a review of patients undergoing total or subtotal
      esophagectomy over a 2-year period, in which pre- and post-anesthesia values of
      seven hepatic function tests, aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma glutamyl
      transpeptidase, total bilirubin, prothrombin time-international normalized ratio,
      and two renal function tests, blood urea nitrogen, as well as serum creatinine,
      were evaluated. RESULTS: Total numbers of patients in PFK or PRK were 51 and 18,
      respectively. In PRK group, duration of surgery was longer than that in PFK
      group, 537 +/- 155 and 453 +/- 67 (min, mean +/- SD), respectively. More patients
      in PRK group required blood transfusion compared with PFK group. There was no
      significant interaction between any hepatic or renal function test and
      anesthesia. In addition, there was no significant difference of increasing rates
      in hepatic and renal function tests between PFK and PRK. CONCLUSIONS: The hepatic
      and renal function after esophagectomy was comparable between PFK and PRK.

PMID- 22991799
TI  - [Use of sugammadex in patients undergoing caesarean section using general
      anesthesia with rocuronium].
AB  - Recently, rocuronium is being used in patients for caesarean section undergoing
      general anesthesia instead of suxamethonium. An increased dose of rocuronium
      improves intubating conditions but prolongs neuromuscular blockade. Sugammadex
      reverses rapidly and predictably even profound rocuronium-induced neuromuscular
      blockade. We experienced 13 cases of caesarean section patients undergoing
      general anesthesia with thiopental (3.5 mg x kg(-1)) and rocuronium (0.9 mg x kg(
      1)). At the end of surgery, sugammadex (2 mg x kg(-1)) was administered every 3
      minutes repeatedly until TOF>0.9. In two patients, neuromuscular blockade
      spontaneously recovered to TOF>0.9 at the end of surgery. In most patients
      administered sugammadex, TOF recovered to more than 0.9 within a few minutes.
      However, in one patient who had chronic renal failure (creatinine clearance rate:
      12 ml x min(-1)), 10 minutes were required for TOF to recover to more than 0.7,
      and TOF never reached 0.9. All patients were successfully intubated at the first
      attempt. No signs of recurarization or adverse effects related to sugammadex were
      noted in the perioperative period.

PMID- 22991800
TI  - [Effects of preoperative oral carbohydrate administration on gastric contents].
AB  - BACKGROUND: Preoperative oral carbohydrate administration for adult patients has
      been recommended by European Society for Parenteral and Enteral Nutrition and
      Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may
      improve patient satisfaction and perioperative glucose metabolism, its effects on
      the gastric contents remain controversial. METHODS: We included 232 adult
      patients without gastrointestinal stenosis or occlusion. Seventy-four patients
      (group A) were not permitted to eat or drink before operation for eight hours,
      while 158 patients (group B) took oral carbohydrate (225 ml, 22.3% glucose) two
      hours before anesthesia induction. After induction, gastric contents were
      aspirated to examine its volume and pH. RESULTS: Although the mean volume of
      gastric contents of the patients in group B was significantly lower than that in
      group A, and gastric pH was also significantly smaller in group B, no patients
      suffered from aspiration during rapid induction. Fasting interval and gastric
      volume were inversely related, and almost all the patients with fasting interval
      above 150 minutes showed gastric contents volume smaller than 25 ml and gastric
      pH more than 2.5. CONCLUSIONS: We conclude that preoperative oral carbohydrate
      can be given safely, although the fasting interval should be 150 minutes in our
      diet regimen.

PMID- 22991801
TI  - [Perioperative fibrinogen concentrations in cardiac surgery with cardiopulmonary
      bypass].
AB  - BACKGROUND: Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB)
      need many blood products due to deficiency of coagulation factors. Blood
      transfusion therapy in patients with excessive bleeding after CPB is generally
      empiric. We checked and studied the fibrinogen concentration and transfusion, as
      well as bleeding amount in the perioperative period. METHODS: The study was
      approved by our institutional ethics committee. Thirty patients were studied.
      Blood samples were obtained at the induction of anesthesia (before CPB), at the
      end of CPB, at the end of operation, and on the next morning, or before the
      patient was given fresh frozen plasma in the intensive care unit. RESULTS: For
      all cases, fibrinogen concentration and platelet concentration were lowest at the
      end of CPB. Fibrinogen concentration rose up to before CPB level on the next
      morning. The group in which fibrinogen concentration was less than 150 mg x dl(
      1) at the end of CPB consumed more blood products than the group with fibrinogen
      concentration of over 150 mg x dl(-1). CONCLUSIONS: Blood transfusion therapy
      based on fibrinogen concentration is needed to maintain adequacy of the
      perioperative blood transfusion and blood conservation in cardiac surgery.

PMID- 22991802
TI  - [Impact of beach chair position on the value of bispectral index during general
      anesthesia].
AB  - BACKGROUND: Although the bispectral index (BIS) has been established as a common
      index of anesthetic depth, there is a possibility that head-up position may
      influence BIS values under general anesthesia. This study examined whether beach
      chair position with 57 degrees head-up would cause the variation of BIS values
      during shoulder surgery. METHODS: Two groups of patients were scheduled for
      surgery, one was supine position group, and the other was beach chair position
      group. Anesthesia was induced with propofol and rocuronium, and maintained with
      sevoflurane (end-tidal concentration 1.0-1.2%). The BIS values were recorded
      manually until 120 minutes after the onset of positioning and evaluated at each
      30 min interval. RESULTS: There was no time-dependent difference in BIS values
      during supine position. In contrast, BIS values in beach chair position group
      showed a marked downward-trend through the measurement period. End-tidal
      anesthetic gas concentration and mean blood pressure did not significantly differ
      between the groups consistently. CONCLUSIONS: To our knowledge, this is the first
      report of the effect of beach chair position on BIS values intraoperatively. This
      result indicates that the beach chair position causes a time-dependent decrease
      in BIS under general anesthesia.

PMID- 22991803
TI  - [Evaluation of preoperative cardiac function for orthopedic surgery by chest CT
      and coronary arteriogram].
AB  - BACKGROUND: In patients with spinal cord diseases, it is difficult to obtain
      stress electrocardiogram and to evaluate preoperative cardiac risk. We evaluate
      these patients by chest CT and if the patients have calcified coronary artery, we
      recommend further testing by coronary arteriogram. METHODS: We evaluated the
      patients who had undergone coronary arteriogram from January 2008 through
      December 2009. RESULTS: In 27 out of 158 cases (17.1%) operations were postponed
      or cancelled. In 12 out of 112 patients with no subjective symptom but with
      coronary calcification operations were also postponed or cancelled. CONCLUSIONS:
      Preoperative chest CT and coronary arteriogram are useful for evaluation of
      preoperative cardiac function.

PMID- 22991804
TI  - [Anesthetic management in a patient with spinal progressive muscle atrophy and
      compromised severe restrictive respiratory dysfunction].
AB  - Spinal progressive muscular atrophy (SPMA) is a rare lower motor neuron disease
      in which anesthetic management is often difficult as a result of muscle weakness
      and hypersensitivity to neuromuscular blocking agents. A 43-year-old female
      patient with SPMA was scheduled to undergo laparotomy for ovarian teratoma. Her
      vital capacity was only 530 ml and % volume capacity was 22.2%, indicating a
      severe restrictive pulmonary disfunction. We selected general and epidural
      anesthesia for the surgery. Anesthesia was induced by propofol and the trachea
      was intubated with additional topical anesthesia. Spontaneous ventilation was
      kept during anesthesia without neuromuscular blocking agents, and systemic and
      epidural opioids were avoided to evade their respiratory depression. Because of
      severe spine scoliosis syndrome, we inserted an epidural catheter into the
      epidural space under radiographic monitoring for safety and precision.
      Postoperative pain control was stable using continuous epidural infusion of 0.2%
      ropivacaine without neurological adverse effects. One day after surgery, the
      trachea was extubated and respiratory function did not aggravate. Despite the
      controversy surrounding the use of neuraxial blocks in motor neuron diseases, in
      this case, epidural anesthesia was useful to keep the respiratory function
      stable.

PMID- 22991805
TI  - [Vanishing glottis cyst following difficult intubation].
AB  - A 68-year-old male patient underwent laparoscopic cholecystectomy under general
      anesthesia. Following anesthesia induction and muscle relaxation, laryngoscopy
      using Macintosh laryngoscope found a tumor of thumb size above the glottis
      completely obscuring the vocal cords. There appeared to be a possibility of tumor
      impaction into the glottis leading to total obstruction when the tumor was pushed
      down by a tracheal tube. Consent was obtained for emergency tracheostomy if
      necessary. The glottis and its surrounding were thoroughly observed using a
      fiberscope via the Fastrach laryngeal mask. The tumor appeared to be a soft cyst.
      A fiberoptic bronchoscope, tentatively introduced into the gap between the cyst
      and the epiglottis, went unexpectedly and smoothly into the trachea. A tracheal
      tube was introduced railroading over it. Information collected so far suggested
      that the patient was able to breathe without tracheal tube. As expected the
      patient did not show any difficulty in breathing and phonation following
      extubation. Seven days afterward, E.N.T. surgeon found no evidence of scarring or
      healing in the throat. The cyst might have been ruptured at the time of
      extubation or afterward, or absorbed.

PMID- 22991806
TI  - [Anesthetic management of a morbidly obese patient in prone position for lumbar
      laminectomy].
AB  - A 22-year-old man weighing 188.7kg, 170cm tall (body mass index 65.2 kg x m(-2))
      with bladder and rectal disturbances due to lumbar disc hernia (L4/5 and L5/S1)
      was scheduled for L4-5 laminectomy under general anesthesia. Awake fiberoptic
      intubation was attempted to prevent airway obstruction because we predicted
      difficult airway. During fiberoptic tracheal intubation, we easily succeeded in
      the insertion of the fiberscope itself into the trachea, and we succeeded in
      placing the reinforced tube into the trachea. Fentanyl and sugammadex were
      calculated with total body weight, but, remifentanil, propofol, and rocuronium
      were re-calculated with ideal body weight. They were given intravenously.
      Anesthesia was maintained with sevoflurane (1.5 to 2.0%), the fraction of
      inspiratory oxygen (about 0.6), remifentanil (0.1 to 0.4 microg x kg(-1) x min(
      1)), and fentanyl (100 to 150 microg) as needed. After turning to prone position,
      severe physiological abnormal signs were not recognized. We concluded that awake
      fiberoptic intubation was useful and safe; moreover, anesthetic agents were
      administrated appropriately for morbid obesity.

PMID- 22991807
TI  - [Successful anesthetic management in a patient with chronic obstructive pulmonary
      disease (COPD) using dexmedetomidine and combined spinal-epidural anesthesia for
      low anterior resection of the rectum].
AB  - A 70-year-old man with a severe COPD was scheduled for low anterior resection of
      the rectum because of rectal cancer. After a week of respiratory rehabilitation,
      respiratory function was much improved. We selected combined spinal-epidural
      anesthesia (CSEA) and dexmedetomidine to preserve spontaneous breathing. We
      obtained appropriate sedative and antianxiety effect without causing respiratory
      depression and hemodynamic changes. Dexmedetomidine was useful for anesthesia for
      a patient with severe COPD without causing respiratory depression.

PMID- 22991808
TI  - [Unexpectedly complicated laryngoscopy caused by a massive mandibular tori].
AB  - Here, we report a case of an unexpectedly complicated laryngoscopy caused by
      massive mandibular tori. A 64-year-old man with mitral regurgitation and aortic
      regurgitation was scheduled for a double valve replacement. Thyromental distance
      and the Mallampati score were used as predictive factors of difficult intubation,
      and both factors were within the normal range. Anesthesia with controlled
      ventilation was started with fentanyl, propofol and vecuronium. After the
      attainment of full muscle relaxation, an experienced anesthesiologist performed
      direct laryngoscopy. It was not possible to intubate the patient under direct
      laryngoscopy because of massive mandibular tori which had not been detected prior
      to induction. Following the failure of direct laryngoscopy, a McCoy laryngoscope
      and a gum elastic bougie were deployed to improve vision. Intubation with a 7.5
      mm tube was successful at the third attempt. We hope our experience will serve as
      a reminder to clinicians that mandibular tori, although benign and without
      subjective symptoms, could have significant effects upon direct laryngoscopy by
      compromising the line of vision. Preoperative oral evaluation is critical and
      aggressive treatment should be considered.

PMID- 22991809
TI  - [Two cases showing the absence of motor evoked potentials without developing
      postoperative paraplegia following thoracoabdominal aortic repair--role of
      epidural cooling, spinal drainage and aorto-iliac side-arm conduit distal
      perfusion].
AB  - We describe two cases which developed loss of motor evoked potentials from
      bilateral lower limbs following thoracoabdominal aortic repair. Paraplegia was
      suspected in both cases; however, one case of Crawford type 2 aneurysm showed
      transient left leg monoplegia with a sensory deficit and the other case of aortic
      pseudoaneurysm showed no neurologic dysfunction postoperatively. We employed
      epidural cooling and spinal drainage for spinal protection and distal perfusion
      was provided through aorto-iliac side-arm conduit. Despite the prolonged spinal
      ischemia during thoracoabdominal aortic repair, spinal drainage and epidural
      cooling were very helpful for protecting the spinal cord from ischemia. The
      interpretation of MEPs seems very difficult especially when the potentials remain
      absent even after reconstruction or reperfusion of segmental arteries, because
      variety of intraoperative factors may affect them.

PMID- 22991810
TI  - [Repeated anesthesia for a patient with Tako-Tsubo cardiomyopathy].
AB  - An 85-year-old woman recieved emergency repair of left obturator hernia under
      general anesthesia. The surgery was completed uneventfully. Shortly after the
      admission to the recovery unit, blood pressure dropped to 80mmHg and ECG showed
      negative T wave. Hypotension was successfully treated with colloid infusion and
      dopamine administration, but negative T wave was unchanged by nitrate infusion.
      The serum CK-MB examination indicated no cardiomyogenic problems. On
      postoperative day 13, she received emergency colostomy under general anesthesia.
      Large negative T wave still persisted. Immediately after induction of anesthesia,
      she showed hypotension, which recovered by fluid infusion and intravenous
      ephedrine. The UCG after surgery showed hypokinesis of the apex of left
      ventricle. She was diagnosed as Tako-tsubo myocardiopathy. One month after the
      second surgery, she received closure of colostomy under general anesthesia
      combined with continuous epidural anesthesia, when negative T wave was seen on
      the ECG. Negative T wave returned to normal 10 weeks after the first surgery.
      When unknown tachycardia and negative T waves are seen, Tako-tsubo cardiomyopathy
      should be considered.

PMID- 22991811
TI  - [Case of anesthesia for thoracoscopic thymectomy in a pediatric patient with
      myasthenia gravis: reversal of rocuronium-induced neuromuscular blockade with
      sugammadex].
AB  - Neuromuscular blocking drugs (NMBDs) can predispose patients with myasthenia
      gravis to postoperative paralysis and respiratory complications. We had a 12-year
      old female patient undergoing thoracoscopic thymectomy. She had suffered from
      MGFA class IIa (mild systemic) myasthenia gravis for 4 months. Anesthesia was
      induced with 3 mg x kg(-1) of thiopental and 0.2 mg x kg(-1) of rocuronium, which
      was given incrementally to achieve 100% blockade. Anesthesia was maintained with
      oxygen, air, 2% sevoflurane and 0.2 microg x kg(-1) x min(-1) of remifentanil.
      0.05 mg x kg(-1) of rocuronium was added when the TOF ratio recovered to 20%.
      Towards the end of the surgery, remifentanil was withdrawn and 4 microg x kg(-1)
      of fentanyl was given. Intercostal nerve block with 0.2% ropivacaine was
      performed to relieve postoperative pain. TOF ratio was 32% at the end, when we
      gave 2 mg x kg(-1) of sugammadex to get 100% reversal of neuromuscular blockade
      in 120 seconds. There was no residual paralysis and respiratory complications
      postoperatively.

PMID- 22991812
TI  - [Anesthetic management for laparoscopic sigmoidectomy in a patient with impaired
      ventricular function caused by cardiac sarcoidosis].
AB  - It has been demonstrated that laparoscopic surgery can reduce surgical trauma and
      postoperative pain, allowing earlier recovery and hospital discharge. However,
      because patients with severe cardiac depression may not tolerate the adverse
      respiratory and cardiovascular effects of pneumoperitoneum with a head-up or head
      down tilt position, laparoscopic surgery has been avoided in these patients. The
      present case with low ventricular function (ejection fraction=23-27%) due to
      cardiac sarcoidosis could successfully undergo laparoscopic sigmoidectomy by
      using pulmonary artery catheterization. Therefore, laparoscopic surgery can be
      performed in patients with cardiac dysfunction if the cardiopulmonary responses
      caused by pneumoperitoneum with a head-up or head-down tilt are sufficiently
      considered and adverse hemodynamic responses appropriately detected and treated
      through invasive monitoring techniques such as pulmonary artery catheterization
      and/or transesophageal echocardiography.

PMID- 22991813
TI  - [Combined subarachnoidal block and continuous femoral nerve block for two
      patients undergoing bilateral simultaneous total knee arthroplasty].
AB  - We administered combined spinal anesthesia plus bilateral femoral nerve block in
      two cases undergoing bilateral simultaneous total knee arthroplasty. Although
      epidural catheters must be removed before anticoagulant treatment can be
      performed after surgery, femoral nerve block, poses minimal hindrance to
      anticoagulant therapy. Because femoral nerve block alone cannot provide
      sufficient postoperative pain relief after total knee arthroplasty, additional
      sciatic nerve block, spinal anesthesia, opioid administration, or some other
      means of analgesia is necessary. A combined femoral nerve block plus sciatic
      nerve block is useful. A large quantity of local anesthetic is required for this
      purpose, and its application is difficult in bilateral simultaneous surgery.
      Spinal anesthesia can be used to reduce the quantity of the local anesthetic, and
      intrathecal morphine can be used to prolong the pain relief. However, intrathecal
      morphine can cause itching and late respiratory depression. Respiratory
      depression did not occur in either of the present patients, although case 2
      experienced some itching. In conclusion, combined bilateral femoral nerve block
      with spinal anesthesia poses minimal hindrance to postoperative anticoagulation
      therapy and enables control of postoperative pain in patients undergoing
      bilateral simultaneous total knee arthroplasty.

PMID- 22991814
TI  - [Case of suspected malignant hyperthermia following local infiltration
      anesthesia].
AB  - A 49-year-old man with no past history of malignant hyperthermia (MH) and
      scheduled for hernia repair was suspected of MH after local infiltration
      anesthesia at other hospital. Although intravenous diazepam was not effective for
      increased body temperature, tachycardia, and convulsion, dantrolene was effective
      for these signs. However, blood test showed no abnormal finding. At our hospital,
      he was scheduled for hernia repair and muscle biopsy under total intravenous
      anesthesia. No event occurred intra- and postoperatively. The examination for
      muscle biopsy revealed that the function of his ryanodine receptor 1 is abnormal.
      The events which had occurred at other hospital were uncertain of being
      associated with MH.

PMID- 22991815
TI  - [Anesthetic management using auto-transfusion and hypothermia for massive
      bleeding].
AB  - A 51-year-old woman was scheduled for emergency enterectomy and vascular repair
      under general anesthesia for active bleeding from internal iliac artery caused by
      repeated radiotherapy for cervical cancer and subsequent hypovolemic shock. For
      the first two hours of operation, the blood loss exceeded 6,000 ml and the
      hemoglobin level decreased to a low of 3.8 g x dl(-1) despite administration of
      38 units of packed red cells. Intraoperative blood salvage was used in order to
      minimize further loss of hemoglobin. Mild hypothermia technique was also
      introduced to prevent brain ischemia. Total bleeding volume was approximately
      10,000 ml, and total transfused volume was 8,740 ml. No neurological deficit and
      no systemic infection were found during the postoperative course. Although
      clinical risks of cell salvage in patients undergoing surgery for malignant tumor
      remain controversial, we conclude intraoperative blood salvage using Cell Saver
      could be utilized as a life-saving means and mild hypothermia might have been
      efficacious for protecting the brain from ischemia in our case.

PMID- 22991816
TI  - [Case of thoracoabdominal stent graft with postoperative paralysis which showed
      dramatic recovery after re-institution of spinal drainage].
AB  - A 62-year-old man underwent stent graft insertion for thoracoabdominal aneurysm.
      We inserted a spinal drainage catheter at L3-4 and started drainage at 10 cmH2O
      at the beginning of surgery. Intravenous naloxone was started from the beginning
      of the operation. Intraoperative course was uneventful, and postoperatively no
      neurological symptoms/signs were noted. The next day, 90 minutes after removal of
      the drainage catheter, sensory loss and muscle weakness of bilateral lower limbs
      developed. A drainage catheter was reinserted, and muscle weakness of the right
      lower limb recovered after 115 minutes, and sensory loss of left lower limb
      recovered after 260 minutes. There was no muscle weakness or paralysis after 300
      minutes. The drainage was continued for the next 48 hours and removed without
      subsequent neurological symptoms and the patient was discharged eight days after
      the operation.

PMID- 22991817
TI  - [Effect on fetal umbilical arterial blood of administration of vasopressors for
      hypotension after spinal anesthesia during cesarean section].
AB  - Spinal anesthesia was performed in 40 patients undergoing cesarean section. When
      systolic blood pressure dropped below 100 mmHg, phenylephrine 100-200 microg (P
      group) or ephedrine 5-10 mg (E group) was administered. The pH of the umbilical
      arterial blood was collected after delivery of the baby. Apgar scores, and
      maternal systolic blood pressure and heart rate before and after each drug
      administration were compared retrospectively. The umbilical arterial pH and Apgar
      scores tended to be slightly higher in the P group, but there was no significant
      difference between the two groups. The rate of blood pressure elevation was 27%
      in the P group and 41% in the E group. The heart rate decreased significantly in
      the P group. There was no significant difference in the systolic blood pressure
      before administration of each drug. Recently, it is reported that the umbilical
      arterial pH is higher in cases in which phenylephrine is used for hypotension
      after spinal anesthesia during a cesarean section. However, the optimal dose of
      phenylephrine is debatable and has not been established. More studies are
      necessary to determine which drugs should be selected according to the maternal
      condition.

PMID- 22991818
TI  - [Two cases of airway stent placement to treat tracheal and bronchial fistula
      using general anesthesia under spontaneous respiration].
AB  - Anesthesia for the tracheobronchial stent placement involves the risk of airway
      narrowing and obstruction. Controlled ventilation with relatively high airway
      pressure is usually used to maintain oxygenation and ventilation during
      anesthesia. However, controlled ventilation does not always provide tidal volume
      and oxygenation due to gas leakage from tracheobronchial fistula. We report 2
      cases of general anesthesia under spontaneous respiration for the airway stent
      placement to treat tracheal and bronchial fistula. Case 1; A 55-year-old man with
      tracheoesophageal fistula due to the esophageal cancer was scheduled for the
      stent placement. Anesthesia was given with dexmedetomidine and sevoflurane
      preserving spontaneous respiration. The surgery was performed without
      complications of hypoventilation and hypoxemia throughout the procedure. Case 2;
      A 71-year-old woman developed empyema with large bronchopleural fistula as the
      result of the complication of radiation for the breast cancer. The stent
      placement was scheduled for closure of the fistula. Anesthesia was induced with
      remifentanil and sevoflurane with spontaneous respiration. When inserting the
      rigid bronchoscope, cough reflex occurred and propofol was added to deepen the
      anesthesia. The stent placement was performed with general anesthesia under
      spontaneous respiration without any complications.

PMID- 22991819
TI  - [Anesthetic management of a patient implanted with a CRT-P device undergoing
      laparoscopic nephrectomy].
AB  - A 76-year-old man implanted with a CRT-P device (cardiac resynchronization
      therapy pacemaker) was diagnosed with renal tumor by chance. Right laparoscopic
      nephrectomy was performed under general and epidural anesthesia. Urologists were
      going to use a monopolar electrocautery during the operation. Before beginning
      the operation, we converted his pacing mode from DDD to DOO with a precordial
      magnet because electrocautery has the potential for causing device reset. His
      blood pressure and heart rate were stable during DOO mode. When the former CRT-P,
      for example InSync8040 (Medtronic) which we reported in 2009, was converted from
      DDD mode to DOO mode, the optimal atrioventricular (AV) delay had become invalid
      in DOO mode. In this case, new device Syncra (Medtronic) which had been marketed
      in March 2011 was implanted. DOO mode could be used keeping the optimal AV delay
      and right ventricular-left ventricular delay and the effect of cardiac
      resynchronization was valid. New CRT-P could be managed as single chamber or
      double chamber pacemaker. Recently in Japan, CRT becomes more common and
      operations in the patients implanted with CRT-P or CRT-D (CRT with
      defibrillation) will become more frequent. CRT will require attention for
      anesthetic management.

PMID- 22991820
TI  - [Case of abdominal compartment syndrome (ACS) associated with perforating
      appendicitis].
AB  - A 4-year-old girl with perforating appendicitis developed abdominal compartment
      syndrome (ACS). Appendicitis in children of preschool age is highly likely to
      rupture, resulting in serious condition. Although we gave priority to systemic
      management in this ACS case since the child showed disturbed consciousness due to
      intracranial hypertension as well as hypercytokinemic encephalopathy. However, we
      should have performed abdominal decompression by laparotomy early. ACS causes
      progressive multiple organ failure through compromising the respiratory and
      circulatory systems and injuring multiple organs, leading to generalized
      inflammatory reactions. We should, therefore, manage ACS patients systemically
      sharing a notion that they must be treated early with abdominal decompression by
      laparotomy.

PMID- 22991821
TI  - [Anesthetic management of a patient with Klippel-Trenaunay syndrome undergoing
      caesarean section].
AB  - Klippel-Trenaunay syndrome (KTS) is characterized by capillary and venous
      malformation and hypertrophy of bone and soft tissues. A 29-year-old
      primigravida, who had been diagnosed of KTS by her hemangiomas and varicosities
      in the right leg, pubic area, rectum, vagina and lower abdominal area, was
      scheduled to receive caesarean section at 37 weeks gestation because vaginal
      delivery might cause hemorrhagic complications and extension of the venous
      lesions. Regional anesthesia was avoided because of the possible injuries of
      unknown venous malformations or varicose veins in the epidural or spinal space.
      The cesarean section was performed under general anesthesia uneventfully and an
      infant was delivered normally. There were no complications such as massive
      hemorrhage, disseminated intravascular coagulation and deep venous thrombosis in
      the perioperative period. Careful anesthetic considerations for the prevention of
      hemorrhagic and thrombotic complications are necessary for cesarean section in a
      patient with KTS.

PMID- 22991822
TI  - [Usefulness of a noncontact continuous tympanic thermometer in patients
      undergoing cardiac surgery using an artificial heart-lung machine].
AB  - BACKGROUND: Most of the thermometers used during operations are invasive and non
      hygienic. The usefulness of a noncontact continuous tympanic thermometer under
      general anesthesia has been reported. We evaluated the usefulness of a noncontact
      continuous tympanic thermometer in patients undergoing cardiac surgery using an
      artificial heart-lung machine. METHODS: Twenty patients scheduled to undergo
      cardiac surgery using an artificial heart-lung machine were selected for this
      study. After induction of general anesthesia, thermistor probes were inserted
      into the rectum and esophagus for measurements of rectal and esophageal
      temperatures, respectively. A noncontact continuous tympanic thermometer was
      inserted into the ear canal on the right side. These temperatures were monitored
      and recorded at one-minute intervals. Regression analysis and Bland-Altman
      analysis were used to compare the data (tympanic/rectal temperatures) with
      esophageal temperature as a core temperature. RESULTS: Tympanic temperature
      showed a good correlation with esophageal temperature (r=0.983, P<0.05). Rectal
      temperature also showed a good correlation with esophageal temperature (r=0.923,
      P<0.05), but the coefficient of correlation was low compared to that of tympanic
      temperature. The mean difference between tympanic temperature and esophageal
      temperature was -0.022 degrees C, and standard deviation (SD) was 0.395 degrees
      C. The mean difference between rectal temperature and esophageal temperature was 
      0.299 degrees C, and standard deviation (SD) was 0.838 degrees C. CONCLUSIONS: A
      noncontact continuous tympanic thermometer is useful for measurement of core
      temperature during cardiac surgery using an artificial heart-lung machine.

PMID- 22991823
TI  - [BRCA1 and DNA damage response].

PMID- 22991824
TI  - [The RhoG signaling pathway].

PMID- 22991825
TI  - [Phosphorylated Rad9 is released from damaged chromatin].

PMID- 22991826
TI  - [Regulation of the DNA-replication stress-response pathways by heat shock protein
      90 (HSP90)].

PMID- 22991827
TI  - [Extra-splicing functions of spliceosome].

PMID- 22991828
TI  - [PACAP as a neuroprotectant].

PMID- 22991829
TI  - [Modifications of fatty acids in lipopolysaccharide].

PMID- 22991830
TI  - [Glial orchestration and execution of neural circuit remodeling during Drosophila
      metamorphosis].

PMID- 22991831
TI  - [Role for the human mediator subunit Med26 in transcription elongation].

PMID- 22991832
TI  - [Topological mass spectrometry analysis for post-translational modifications in
      pituitary hormones].

PMID- 22991833
TI  - [An optimum method for generation of functional recombinant apoptosis inhibitor
      of macrophage (AIM) protein].

PMID- 22991834
TI  - [Molecular targeting drugs].

PMID- 22991835
TI  - [Role of VEGFR-TKIs in the treatment of renal cell carcinoma].

PMID- 22991836
TI  - [Role of mTOR inhibition in the treatment of metastatic renal cell carcinoma].

PMID- 22991837
TI  - [Update on treatment of multiple myeloma: including myeloma kidney and molecular
      targeting drugs].

PMID- 22991838
TI  - [Beneficial effects of rituximab in the treatment of refractory nephrotic
      syndrome].

PMID- 22991839
TI  - [Molecular targets and their regulation in systemic lupus erythematosus and lupus
      nephritis].

PMID- 22991840
TI  - [Molecular targeting therapy in rheumatoid arthritis].

PMID- 22991841
TI  - [New perspective for drug discovery and clinical development in kidney disease].

PMID- 22991842
TI  - [Case of trimethoprim-induced hyperkalemia complicating ANCA-associated
      vasculitis].
AB  - A 76-year-old man was admitted to our hospital because of severe anemia. Routine
      screening revealed a sigmoid adenocarcinoma, and he underwent sigmoidectomy. Post
      operatively, he developed rapidly progressive glomerulonephritis. He was positive
      for myeloperoxidase anti-neutrophil cytoplasmic antibody. A renal biopsy revealed
      idiopathic crescentic glomerulonephritis of the pauci-immune type. He was treated
      with methylprednisolone semi-pulse therapy with clinical improvement. After the
      steroid pulse therapy, he was given oral prednisolone, 40 mg per day, and oral
      trimethoprim (TMP), 160 mg, and sulfamethoxazole (SMX), 800 mg twice weekly for
      chemoprophylaxis against pneumocystis pneumonia. One month after the initiation
      of TMP/SMX, he developed hyperkalemia and hyponatremia. His transtubular K
      gradient was low, and urinary potassium excretion was decreased. On the other
      hand, plasma renin activity and plasma aldosterone concentrations were within
      normal limits. These results suggested that TMP acted similarly to a potassium
      sparing diuretic amiloride and reduced renal potassium excretion. Administration
      of calcium polystyrene sulfonate resulted in correction of the hyperkalemia
      without discontinuation of TMP/SMX. We emphasize that patients with impaired
      renal function are at the significant risk of developing trimethoprim-induced
      hyperkalemia even with chemoprophylaxis.

PMID- 22991843
TI  - [Case of purpura nephritis accompanied by idiopathic cholesterol embolism].
AB  - A 69-year-old man with a history of hypertension was admitted to our hospital
      because of proteinuria, renal dysfunction, and both purpura and edema in the
      lower extremities. Laboratory data on admission revealed proteinuria (3.4 g/day),
      microscopic hematuria (3+), and renal dysfunction (serum creatinine 1.47 mg/dL).
      In the renal biopsy, all glomeruli showed mild mesangial proliferation. A few
      glomeruli showed mild segmental endocapillary proliferation. Crescent was not
      found in any glomeruli. Immunofluorescent study revealed the deposition of IgA
      and C3 in the mesangial area. In addition, jagged-edged angular cholesterol
      clefts of atheromatous emboli were seen in a small artery with tubular atrophy
      and fibrosis. He was diagnosed as Henoch-Schonlein purpura nephritis accompanied
      by idiopathic cholesterol crystal embolism, because he previously had not
      undergone any cardiac procedures (e. g., percutaneous coronary intervention and
      coronary artery bypass grafting) and anticoagulating therapy. Oral prednisolone
      (40 mg/day) effectively decreased proteinuria and improved his renal dysfunction.
      In this case, renal dysfunction may be related to the ischemic interstitial
      damage caused by cholesterol crystal embolism, as well as purpura nephritis.

PMID- 22991844
TI  - [Case of lupus nephritis complicated with hemophagocytic syndrome].
AB  - A 27-year-old woman was referred to our hospital because of pancytopenia and
      nephritic syndrome in November, 2008. The findings of physical and laboratory
      examinations showed systemic lupus erythematosus (SLE). Diffuse proliferative
      lupus nephritis(group IV-G(A))was confirmed by renal biopsy. After combined
      therapy with prednisolone, intravenous cyclophosphamide pulse and mizoribine,
      proteinuria decreased from 13.0 g/day to 2.0 g/day and the serum complement level
      recovered to the normal level. However, she visited our hospital again for
      management of bleeding tendency in July 2009. She was diagnosed as hemophagocytic
      syndrome (HPS), with pancytopenia, high ferritin, high LDH level and
      hemophagocytosis in the bone marrow. She was treated effectively with steroid
      pulse therapy, but relapsed with HPS after two weeks. Although her child caught a
      cold, the case did not show any sign or symptom of infection, such as the common
      cold. However, we diagnosed her HPS as infection-associated hemophagocytic
      syndrome (IAHS) because she was not in the active phase of SLE at the onset of
      hemophagocytosis and the laboratory findings showed elevation of her serum
      ferritin and LDH. Therefore, we considered that her infectious sign may have been
      concealed by immunosuppressive therapy with prednisolone for SLE. It is very
      difficult to distinguish between IAHS and autoimmune-associated hemophagocytic
      syndrome (AAHS)in autoimmune diseases, but the differential diagnosis is
      necessary to treat the HPS. Here, we report an important case of HPS complicated
      with SLE. This case may attract interest particularly in the management of HPS
      complicated autoimmune disease. Therefore, we report it with a review of the
      literature.

PMID- 22991845
TI  - [Detection of parechovirus in infectious gastroenteritis patients from Kanagawa
      Prefecture Region. Fecal specimens sent from the pediatric sentinel clinics from
      April 2008 to March 2011].
AB  - To clarify the causative viruses of infectious gastroenteritis, fecal specimens
      were sent from the pediatric sentinel clinic in Kanagawa Prefecture except for
      Kawasaki City, Yokohama City, Yokosuka City, Sagamihara City, and Fujisawa City.
      About 50% of fecal specimens were not negative for causative viruses. A total of
      374 fecal specimens which were known to be negative for rotavirus, adenovirus,
      norovirus, sapovirus, and astrovirus were tested for human parechovirus (HPeV).
      HPeVs VP1 genes were detected in 15 samples from 374 fecal specimens which were
      tested from April 2008 to March 2011. Sequencing analysis of a 800-nt portion of
      the HPeV VP1 gene of these 8 strains and 7 specimens from April 2008 to March
      2011 showed that one specimen in Septenber 2008 was classified as HPeV4 and 14 of
      the others were classified as HPeV1.

PMID- 22991846
TI  - [Characterization of a nonspecific inhibitor found in human sera raised against
      the 2006/07 influenza vaccine strain A/Hiroshima/52/2005 (H3N2) virus].
AB  - The serology of influenza viruses typically uses hemagglutination inhibition (HI)
      or the neutralization test (NT). However, the sera of many humans and animals
      contain nonspecific inhibitors of hemagglutinin that must be inactivated or
      removed from the serum before use in the HI assay. Any nonspecific inhibitor in
      human serum is typically inactivated by pre-treatment with receptor-destroying
      enzyme (RDE). However, during the 2006/07 influenza circulating season, we
      observed that influenza vaccine strain A/Hiroshima/52/ 2005 (H3N2) exhibited
      susceptibility to an RDE-resistant inhibitor in human serum. We report herein on
      a preliminary characterization of this inhibitor, including the development of a
      novel inhibitor-inactivating technique for pre-treatment of human serum to be
      used for HI with the A/Hiroshima/52/2005 (H3N2) virus.

PMID- 22991847
TI  - [The possibility of outbreak control by real-time surveillance with PCR method
      perfomed immediately--a case study of hand foot and mouth disease outbreak in a
      day care facility for children].
AB  - OBJECT: We examined the relationship between syndromic surveillance and
      laboratory confirmation, at an early stage of an outbreak of hand foot and mouth
      disease and RS virus infection. METHOD: We observed the epidemiological situation
      from a surveillance system at a day care facility for young children in Tokyo
      from one week before onset of the indicator until one month thereafter. For
      laboratory diagnosis, we collected a rectal swab or a nasal swab from one patient
      in the early stage of the outbreak. RESULT: A total of 20 patients, comprising 12
      1-year-old, 5 2-year-old and 3 3-year-old children, were found to have hand foot
      and mouth disease on August 1st, 2011. From a rectal swab from one HFMD patient,
      enterovirus genome was detected and identified as coxsackievirus type A6 (CA6)
      with PCR sequencing. The CA6 had 99% identity to CA6 (Genbank No AB663318) in the
      VP4 coding region. RS virus also was detected from a nasal swab. DISCUSSION: The
      establishment of a surveillance system at day care facilities for children can
      monitor infectious diseases among young children promptly. Laboratory
      confirmation, even though from only one patient as shown in this study, can
      provide critical information regarding the causative agent of the outbreak. This
      method is easy to conduct and could be used for activating appropriate
      countermeasures. CONCLUSION: We believe that the combination of the timeliness of
      a surveillance system at day care facility for children and the convenience of
      laboratory diagnosis of even one patient can detect the causative pathogen, and
      thus enable the activation of countermeasures before an outbreak become
      widespread.

PMID- 22991848
TI  - [A case of MRSA infection in multiple artificial joints successfully treated with
      conservative medical treatment].
AB  - We report herein on a case with multiple MRSA prosthetic arthritis and
      osteomyelitis successfully treated medically. Our patient was a 64-year-old
      Japanese woman with a previous medical history of malignant rheumatoid arthritis
      and multiple surgical interventions with an atlantoaxial fixation in 2003,
      artificial joint replacement of both knee joints in 2006, and of the right hip
      joint in September, 2007. She was initially hospitalized due to MRSA arthritis in
      the right hip in October, 2007. Thereafter, multiple joint infections occurred
      sequentially in the right knee joint in January 2008 and the left hip joint in
      June 2008. More recently, the patient was re-admitted in January 2009 due to
      cervical osteomyelitis with MRSA infection. The patient had been treated with a
      combination of vancomycin and rifampin for 17 weeks and followed by
      sulfamethoxazole/trimetoprim in the out-patient setting up to the present.
      Although the complete resolution of multiple deep MRSA infections with prosthetic
      arthritis and osteomyelitis is not expected without removing the infectious
      sources, our patient was successfully treated with chronic antibiotic suppressive
      therapy. Therefore, we report on our case with a literature review.

PMID- 22991849
TI  - [Syphilis proctitis complicated with HIV infection: a case report].
AB  - We report on a 26-year-old Japanese man who was referred to our hospital because
      of anal pain and hematochezia. On admission, in addition to his gastrointestinal
      symptoms, a generalized maculopapular rash was observed, involving the palms of
      his hands and soles of his feet. His history and physical examination were
      compatible with syphilis, confirmed by a high syphilis titer on blood
      examination. Further tests revealed the presence of HIV infection, with a CD4
      cell count of 227/microL. Colonoscopy demonstrated a deep ulcer in the lower
      rectum, although biopsy specimens did not reveal any syphilis spirochetes, or any
      other specific microorganisms. Intravenous penicillin G was initiated, resulting
      in a dramatic improvement of the ulcers along with the skin lesions confirming
      the diagnosis of syphilis proctitis. A rapid plasma reagin titer test performed 3
      months after treatment demonstrated significant decrease, indicating successful
      treatment.

PMID- 22991850
TI  - [A case of Stevens-Johnson syndrome (SJS) progressive toxic epidermal necrolysis
      (TEN) onset during hyposensitization therapy for pulmonary tuberculosis
      complicated with dermatomyositis].
AB  - A 58-year-old female with a history of dermatomyositis was receiving large oral
      doses of steroids. She had pulmonary tuberculosis and developed a fever, systemic
      exudative erythema, exanthema, and epidermolysis covering 30% of her body surface
      area while being treated with four agents, including isoniazid (INH) and
      rifampicin (RFP). Histopathologically, eosinophilic necrosis was observed in all
      layers of the epidermis and a diagnosis of Stevens-Johnson syndrome (SJS)
      progressive toxic epidermal necrolysis (TEN) was made. The drugs suspected in the
      drug-induced lymphocyte stimulation test (DLST) re-testing were INH and RFP, and
      the DLST was considered to be important during the recovery period as well as in
      the acute phase. Early treatment with plasma exchange therapy and large
      quantities of intravenous immunoglobulin (IVIG) was successful. Plasma exchange
      therapy and IVIG are extremely effective when SJS and TEN occur in a patient
      already on high-dose steroid therapy. Note that the incidence of SJS and TEN is
      believed to be higher in patients with collagen disease, such as in our case, as
      compared to the general population.

PMID- 22991851
TI  - [Evaluation of immunochromatographic detection kit for novel human adenovirus
      type 53, 54 and 56].

PMID- 22991852
TI  - [Intravenous azithromycin for treatment of an uncomplicated typhoid fever
      suspected primary treatment failure].

PMID- 22991853
TI  - [Clinical features associated with sudden hearing loss in children].
AB  - Sudden sensorineural hearing loss is usually unilateral, and the cause is not
      identified in most adult cases. However, a specific cause has frequently been
      found in the case of children, in whom idiopathic sudden sensorineural hearing
      loss (ISHL) is comparatively rare. We investigated 20 cases of acute unilateral
      sensorineural hearing loss in children associated with a certain disease, but
      which was first diagnosed as ISHL. Thirteen patients aged 6 to 16 years old were
      diagnosed as having psychogenic (functional) hearing loss. Discrepancies in
      behavioral and objective tests are most valuable when functional hearing loss is
      suspected. Elevated pure-tone thresholds associated with normal distortion
      product otoacoustic emissions (DPOAEs) enable prompt further investigation. There
      are several conditions that may mimic functional hearing loss, so auditory
      brainstem response (ABR) testing is necessary to verify the actual cause. The
      unilateral profound hearing loss in 2 patients aged 7 and 11 years old was due to
      asymptomatic mumps proven by detecting the mumps IgM antibody. Total hearing
      recovery in the 125-1000 Hz frequencies occurred in one case. In 5 patients aged
      6 to 12 years old with acute hearing loss and vertigo, high resolution CT imaging
      showed an abnormally enlarged vestibular aqueduct on the affected side. Large
      vestibular aqueduct syndrome should be considered in acute high-frequency sloping
      hearing loss with an A-B gap at low frequencies.

PMID- 22991854
TI  - [Case of acute pharyngitis caused by Corynebacterium ulcerans in Ibaraki
      Prefecture].
AB  - We report on the case of a 51-year-old woman who presented with refractory
      pharyngitis caused by toxigenic Corynebacteriumn ulcerans (C. ulcerans). Thick
      pseudomembrane formations and yellowish pus were observed in her nasopharynx.
      Based on her clinical course and history of breeding cats, we considered C.
      ulcerans infection as the possible diagnosis. She was treated with macrolide
      administration and her symptoms immediately improved. C. ulcerans was identified
      in pus from the patient's pharynx as well as in discharge material from her cat's
      eyes, and C. ulcerans was thought to have caused her pharyngitis. C. ulcerans is
      one of the infecting bacteria which can cause a zoonotic infection. In Japan,
      some cases with C. ulcerans infection from cats have been reported. It is
      important that we should consider C. ulcerans infection as a differential
      diagnosis of refractory pharyngitis.

PMID- 22991855
TI  - [Intralabyrinthine schwannoma extending into the round window niche and internal
      auditory canal].
AB  - Intralabyrinthine schwannomas (ILSs) are rare benign neoplasms arising from
      distal branches of the cochlear, superior vestibular, or inferior vestibular
      nerves. We report on a case of ILS with extensions to the round window niche and
      internal auditory canal (IAC) in a 47-year-old male. The patient noticed sudden
      hearing loss and tinnitus in his left ear at the age of 36, received steroid
      therapies, but was left with complete deafness. He had suffered from repetitive
      vertigo attacks for 6 months at 41. At 46 when he presented with deterioration of
      his left tinnitus, he was finally diagnosed as having ILS on enhanced MRI and
      constructive interference in steady-state analysis. The tumor was located in all
      turns of cochlea, vestibule, and the fundus of the IAC. Because follow-up MRI
      suggested growth of the IAC tumor, we performed total removal of the tumor via
      the translabyrinthine and transcanal approaches. The tumor had invaded only the
      cochlear nerve in the IAC and appeared in the round window niche in the middle
      ear. Pathological examination showed an Antoni A type schwannoma with fibrous
      changes of the semicircular canals. We should remember this inner

PMID- 22991856
TI  - [New horizons in pediatrics].
AB  - The profession of pediatrics is constantLy changing. New morbidities are
      replacing old ones, as a reflection of the changes in society. Even today, old
      and rare morbidities, like scurvy or acute urinary retention, can be encountered
      in special settings and populations such as handicapped and developmentally
      delayed children. The availability of ever newer genetic tests highlights the
      duty of pediatricians to constantly update families for carrier detection, but
      also raises questions on the cLinical significance of asymptomatic mutations.
      Vaccination is one of the most effective pubLic health measures, but failure of
      medical staff to follow self vaccination recommendations might jeopardize
      protecting the children. Anti vaccination movement is rapidly growing due to the
      Internet. However, we must acknowledge the benefits inherent in Internet forums,
      for example, adolescents consulting anonymously regarding pubertal issues. A new
      and most needed aspect of care is treatment of pain in children. Increased staff
      awareness concerning anaLgesia is needed as well as promoting the use of medical
      clowns for anxiety and pain provoking procedures. Delivering appropriate
      healthcare to different societal demographic sectors is a challenge for
      pediatricians. The approach to fever phobia among ultra orthodox parents and
      advocacy for safety recommendations in the Arab population are two such exampLes.
      Finally, we shouLd always strive for innovative approaches in pediatric diseases
      affecting quality of life, and celiac disease is certainly promising in this
      direction.

PMID- 22991857
TI  - [Acute urinary retention in children].
AB  - Acute urinary retention is defined as failure to urinate in spite of an adequate
      amount of urine in the bladder. Acute urinary retention in children is rare, and
      may cause pain and distress. Diagnosis and urgent treatment are essential.
      Identification and treatment of underlying medical conditions such as
      constipation, neurological impairment or adverse reactions to medications may
      prevent recurrence of retention. We describe six cases of children who were
      hospitalized with acute urinary retention and review the medical literature on
      the subject.

PMID- 22991858
TI  - [Eat a citrus fruit, stay healthy--a case report of scurvy].
AB  - Scurvy is a disease that results from a vitamin C deficient diet. Since vitamin C
      is available in many food products, and especially in citrus fruits, the disease
      is rare in developed countries. Clinical manifestations of scurvy include general
      weakness, cutaneous and gum bleeding, pain in the lower limbs and inability to
      stand and walk (pseudo paralysis). The diagnosis of scurvy requires a high level
      of clinical suspicion, typical radiographic features and low Levels of vitamin C
      in the plasma. We report a case of a 7-year-old patient with a medical history of
      hydrocephalus, failure to thrive and severe psychomotor retardation due to
      complications of prematurity. On admission she had gum bleeding, severe anemia,
      pain in the lower limbs and refused to stand and walk. According to her parents,
      her diet was restricted, without vegetables or fruit consumption. Our
      investigation ruled out coagulopathy, malignancy and infection. Serum vitamin C
      levels were low and radiographic findings were consistent with the diagnosis of
      scurvy. The patient improved rapidly after the initiation of vitamin C
      supplements. Despite being rare, scurvy should be considered in the differential
      diagnosis of bleeding and pain in the lower limbs, especially in a malnourished
      patient.

PMID- 22991859
TI  - [Asymptomatic classical hereditary xanthinuria type 1].
AB  - We report on a girl who was diagnosed with classical hereditary xanthinuria due
      to an incidental finding of extremely low Levels of uric acid in the blood. The
      girl is compLetely asymptomatic. Hereditary xanthinuria is a rare autosomal
      recessive disease that usually causes early urolithiasis but may cause rheumatoid
      arthritis-like disease and even be associated with defects in the formation of
      bone, hair and teeth. In Israel it has mostly been described in patients of
      Bedouin origin. Throughout the world, only about 150 cases have been described;
      about two thirds of these patients were asymptomatic. Since the clinical
      presentation and age of symptom appearance are diverse, the case raises questions
      as to the required follow-up of these patients and as to whether a low oxalate
      diet should be initiated.

PMID- 22991860
TI  - [Medical clowns--dream doctors as important team members in the treatment of
      young children with juvenile idiopathic arthritis].
AB  - Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease
      in children. An intra-articular corticosteroid injection (IAS), one of the
      cornerstones of treatment for this disease, is usuaLLy associated with anxiety
      and pain. A major part of the success in reducing the pain is associated with the
      level of the child's anxiety even before starting the procedure. This is a case
      study of a 5 year old girl with JIA, who has been treated with an intra-articular
      corticosteroid injection to her knee joint. The case study is presented from the
      point of view of the medical clown, who is an important integral part of the team
      of the IAS procedure. In this article we will discuss the participation of
      medical clowns in the treatment of children in general, and in the IAS procedure
      in particular. The importance of the subject stems from the fact that it has been
      proven that the presence of medical clowns significantly alleviates the
      children's anxiety and pain. This study, as well as others on this subject, shows
      that we should encourage medical clowns as an integraL part of the treatment of
      children.

PMID- 22991861
TI  - [Fever phobia in the ultra-religious community in Israel].
AB  - INTRODUCTION: Fever phobia has been described for over 30 years without
      significant prevalence change. NevertheLess, there is only minimal data about
      this phenomenon in IsraeL and within its varied sub-populations. The study goal
      was to examine the prevalence of this phobia among parents seeking care for their
      febrile child in an urgent care center (UCC), especialLy Charedi (ultra
      religious) parents. The working hypothesis was that as the Charedi parents tended
      to be younger, and have Less formal education, they would be more LikeLy to have
      greater rates of fever phobia. METHODS: Site: Two UCCs in Jerusalem and Modiin.
      INSTRUMENT: A structured 38-item interview was conducted encompassing the
      original fever phobia questionnaire, demographic information, and knowledge and
      beliefs regarding fever. PARTICIPANTS: Parents of children who visited a UCC with
      a febrile child aged between 2 months and 10 years. RESULTS: A total of 349
      interviews were conducted; 90% of the parents felt that fever could cause damage;
      33% were very worried when their child has fever; 55% worried and 12% were not
      worried. It was found that there was lack of knowledge and false assumptions
      existed. For example, 1/3 of the parents defined fever < 37.7 degrees C as fever
      and 1/2 of the parents start treatment for fever < 38 degrees C. n contrast to
      the working hypothesis, the Charedi parents were less worried. The larger the
      family, the less likely the parents were to be worried. CONCLUSIONS: There
      continues to be both lack of knowledge and incorrect assumptions regarding fever
      in parents using UCC. Charedi parents are less worried, perhaps secondary to
      larger family size.

PMID- 22991862
TI  - [Adolescents ask physicians on the Internet: a one-year survey of adolescents'
      questions on health issues in an Internet forum].
AB  - INTRODUCTION: During the past decade, the internet has become a major information
      resource in various domains of life and a communication venue among young people
      and adolescents who seek health information via the internet. Until now, the
      contents of Israeli adolescents' questions regarding health issues on internet
      sites have not been published. PURPOSES: (1) A survey of the characteristics of
      adolescents who seek health information and their questions presented to the Ynet
      forum "The body during adolescence". In this forum physicians experienced in
      adolescent medicine respond to these questions and to comments of other forum
      participants. (2) Presentation of problematic issues in professionals' responses
      to health questions in the internet. METHODS: Survey of a representative sample
      of contacts to the Ynet forum "The body during adolescence" during 2009 gathering
      information on gender and age of contacting person, parents' contacts, contacts'
      contents and physicians responses. RESULTS: A total of 412 contacts were
      surveyed, 210 (51%) females, aged 14-17 years--60%, 10-13 years--17% and 18-21
      years 15%. Parents' questions appeared in 39 (9%) of contacts. Of all contacts,
      44% related to sexuality issues and 17% related to self image and body
      composition. The physicians provided complete responses to 60% of the contacts,
      while in 40% the physician's responses included referral to clinical medical
      consultation. CONCLUSIONS: An internet health forum enables adolescents and
      parents to ask questions and raise doubts and anxieties regarding various health
      issues without the fear of being exposed and enables them to express their
      concerns face-to-face with a healthcare provider Sensitive issues regarding
      sexuality and self-image, which are not raised frequently during clinical
      encounters, are expressed and receive professional responses in the forum.
      Notwithstanding the significance of a rapid professional contribution, physicians
      responding to contacts in internet forums need to recognize the barrier related
      to professional communication with persons whom they have not met and for whom
      follow-up is impossible.

PMID- 22991863
TI  - [Influenza vaccination of pediatric staff as a predictor for recommendations to
      children].
AB  - BACKGROUND: As of February 2010, the 2009 H1N1 influenza has caused more than
      15,000 deaths worldwide. Seasonal influenza vaccination rates among health care
      workers (HCW) have been universally low; the 2009 H1N1 influenza vaccination of
      HCW has also been disappointing. In several studies, a correlation between HCW
      seasonal influenza vaccination status and vaccine recommendation to adult
      patients was found. OBJECTIVE: To examine the correlation between the declared
      influenza vaccination status of pediatric staff and vaccine recommendations to
      their patients. METHODS:  INSTRUMENT: Anonymous questionnaire concerning
      attitudes and practices regarding seasonal and 2009 H1N1 influenza vaccination.
      RESPONDENTS: 141 pediatric staff attending a conference. RESULTS: Seventy two
      percent of the respondents had been or intended to be vaccinated against seasonal
      influenza, 62% against the 2009 H1N1 influenza, and 56% against both diseases.
      Ambulatory setting employment was positively associated with the recommendation
      of seasonal influenza vaccination to all children. By multivariate Logistic
      regression analysis, the "vaccinated or intending to be vaccinated against
      seasonal influenza" was the only significant independent variable associated with
      recommending universal pediatric seasonal influenza vaccine (OR=15, 95% CI 6.1
      41.4, p < 0.001). Similarly, "being or intending to be vaccinated against the
      2009 H1N1 influenza" was the only significant independent variable associated
      with recommending universal pediatric vaccination against this disease (OR = 5.2,
      95% CI 1.85-14.6, P = 0.002). CONCLUSION: A strong correlation between the
      influenza vaccination status of pediatric staff and the recommendation of the
      vaccines to children emphasizes that intense education of providers is a crucial
      step in assuring a positive recommendation to families.

PMID- 22991865
TI  - [Childhood injuries in Israel--current status and the role of the community
      pediatrician].
AB  - In Israel, as in other developed countries, injury is a major problem in
      children's health. Injuries are a main cause of morbidity and mortality of
      children in all age groups, both genders, Jews and Arabs and is also a Leading
      cause of disability and loss of potential life years. In Israel, every year
      injuries account for 144 child deaths, approximately 24,000 hospitalizations and
      about 182,000 ED visits, and it is estimated that about half of all Israeli
      children sustain an injury requiring primary medical care in the community. The
      vast majority of those injuries are unintentional. The leading cause of child
      death from injury is traffic accidents, while home and Leisure accidents are
      common causes for children's hospitalization due to injury. The death rate is
      higher among children from low socioeconomic clusters compared to high
      socioeconomic clusters. Between 2000 and 2008, there was a decrease in child
      death rates from injury and unintentional injury. Intervention programs involving
      the safety education of parents by community pediatricians showed effectiveness
      in increasing safe behaviors and prevention of child injuries. In Israel several
      programs for injury prevention are implemented in the health system, including
      parents' education in well-baby clinics for child safety by nurses. Since the
      community pediatrician is a significant factor in parents' decisions regarding
      their child's health, it is recommended that he will also educate them concerning
      child injury prevention.

PMID- 22991864
TI  - ["But I have done the genetic tests...". The obligation to identify genetic
      carriers and prenatal genetic tests for new mutations].
AB  - INTRODUCTION: Genetic tests are developing quickly. Therefore, genetic screening
      tests which were carried out before the first pregnancy are not always sufficient
      for the subsequent pregnancies. Familial dysautonomia (FD) is a disabling
      autosomal recessive disorder affecting Ashkenazi Jews in which the carrier
      frequency varies from 1:17 to 1:32. In 2001, the FD gene was discovered and the
      genetic tests were made available in most Israeli hospitals or institutes. In
      2008, the FD genetic test was included in the "health basket" by the Israeli
      Ministry of Health. AIMS: Investigating the reasons for new FD patients born
      after 2001 as a model for other genetic diseases. METHODS: A retrospective study
      was performed from medical chart data. RESULTS: Since 2001, forty FD patients
      were born to Israeli parents. Eleven patients were born to mothers who had
      undergone genetic tests before 2001, however, they were not informed that new
      genes had been discovered. This has led to a number of law suits. Furthermore,
      the FD test was not offered to another woman who had some of the genetic tests
      performed after 2001. Religious parents of 9 FD patients had married long before
      the FD genetic test became avaiLable. Four children were born to families who
      were unaware that there was an FD patient in their extended family. DISCUSSION
      AND SUMMARY: The burden on the patients, families and the National Health Service
      for treating FD and other genetic diseases is enormous. Updating new genetic
      information might prevent new cases. CONCLUSIONS: Before each new pregnancy, it
      is necessary to update the population about new genetic tests.

PMID- 22991866
TI  - [Pain in children in the 21st century].
AB  - Pain is undertreated in children due to historical reasons. The pain afferent
      tracts are developed in 21 weeks of gestation and it is well documented that
      preterm and neonates can experience pain. Pain in neonates leads to ncreased
      distress and altered pain response later in life. pain assessment in children is
      chalLenging. In the preverbal age using scales combining physiological and
      behavioral parameters help estimating the pain. Older children can use VAS scales
      but their pain scoring is affected by developmental age changes. Children respond
      to pain management treatments differently than adults. Some medications are not
      approved for use in children. Non-pharmacologic treatment is more effective,
      while invasive treatment such as regional nerve blocks for chronic pain is Less
      effective in children. Chronic pain is ignored or overlooked in children. This
      can lead to physicaL, emotional, psychological and social effects. Children may
      be absent from school and withdraw from their friends. Children with chronic pain
      will most likely become adults with chronic pain. Accepting chronic pain in
      children as a real problem and attempting to treat it at a young age may help
      decrease rates of adult pain in the future. The family doctor may be looking for
      serious causes for the pain. Referrals to specialists can Leave children without
      proper pain management or treatment. The Pediatric Pain Clinic is a
      multidisciplinary program specifically aiming to provide treatment and support
      for acute and chronic pain in children to conquer pain, help children to cope
      with chronic pain and avoid future complications.

PMID- 22991867
TI  - [Future therapeutics in celiac disease].
AB  - Celiac disease is a common autoimmune disease affecting 1% of the Western
      populations. It is an inappropriate immune response, in genetically susceptible
      patients to dietary wheat, rye, barley and oats. Treatment involves a Lifelong
      gluten-free diet that predisposes to low compliance due to limited variety, high
      cost and low palatability, imposing social pressure and affecting quality of
      life. The result is an urgent need for alternative therapeutic strategies. Based
      on the growing actual knowledge on the intestinal inflammatory cascade, mucosal
      immunology and genetics of celiac disease, new attractive potential therapies are
      emerging. Possibilities include: searching for low immunogenic wheat variants or
      strains pretreated with enzymes or binders for lower toxicity. Other strategies
      involve decreasing transepithelial uptake or dampening of the adaptive immune
      response by transglutaminase inhibitors or blockage of the HLA groove and immune
      modulation to shift the TH1 to TH2 profile. Developing biological therapy aims to
      decrease intestinal homing, adhesion and activity of inflammatory cells,
      counteract the pro-inflammatory cytokines, clonal intestinal T cells or
      mesenchymal stem cell replacement or mitogenic intestinal repair safety, cost,
      affordability and clinical effectiveness are of prime concern. Most of the above
      strategies showed promising results ex-vivo. The future will highlight the in
      vivo winner.

PMID- 22991868
TI  - [Risk-sharing scheme in Israel--Kuvan as an allegory].
AB  - Healthcare systems worldwide are dealing with the uncertainty characterizing new
      and expensive health technoLogies, particularly aspects involving drug
      effectiveness and the extent and doses required for utilization. Reducing this
      uncertainty can be achieved mainly by using either coverage with evidence
      development methods or risk-sharing schemes (RSS). In 2011, the first
      phenylketonuria (PKU) risk-sharing scheme was set up in Israel, through the
      public funding health services updating process. This was done in order to ensure
      that people with PKU could access PKU sole treatment--sapropterin
      dihydrochloride, Kuvan. The apparent effectiveness of the treatment, on one hand,
      and the uncertainty regarding the number of patients and average treatment
      dosage, on the other hand, dictated the RRS. This scheme determined a ceiling
      number of tablets to be funded by the insurer, above this ceiling the
      manufacturer would finance Kuvan. Furthermore, it was agreed that after 3 years
      Kuvan would be brought to the public committee for updating reimbursement
      decisions. It is inevitable that risk sharing and conditional coverage agreements
      will become a common practice in the reimbursement process in the future. This
      will allow competent authorities and pharmaceutical companies to build clinical
      experience and other required data with medicines which might normally not be
      eLigible for reimbursement. Before it becomes the common practice in Israel, the
      RSS for Kuvan, process and outcomes, should be monitored and analyzed by the
      Ministry of Health, to ensure patients access to treatment, the effective
      collection of the research data and the effective interaction between Israel's
      four health funds and the manufacturer.

PMID- 22991869
TI  - [Risk-sharing schemes: a new paradigm in adopting innovative pharmaceuticals].
AB  - In recent years, spending on prescription drugs contributes substantially to the
      continuous growth in health expenditure in most Western countries. This increase
      in spending is influenced by both a rise in the use of existing drugs and by the
      adoption of new and expensive drugs. Risk-sharing agreements between
      pharmaceutical companies and health insurers have emerged as insurers began to
      deny reimbursement of expensive innovative treatments with unfavorable cost
      effectiveness ratios. This occurred in cases where the expected budgetary impact
      was too high or when the long-term effectiveness was questionable. Risk sharing
      agreements serve the interests of both the insurers and the drug manufacturers.
      Pharmaceutical companies' interests are to dispel the uncertainties encountered
      by the health insurers white deciding on drug reimbursement. The insurers are
      interested in these agreements in order to reduce the budgetary risk while
      allowing their patients access to innovative drugs. Currently, only a few risk
      sharing agreements have been implemented, and the scientific literature on such
      schemes is still sparse. Since the health insurers' interest is to develop
      mechanisms that will contain health costs, without affecting the insured, it
      appears that this trend will continue to emerge. It is also likely that the
      adoption of similar mechanisms in the Israeli National List of Health Services
      updating process, would improve the accuracy of early estimates of the budgetary
      impact, and the actual use of the new technologies would be close to early
      estimates. This article reviews the principles of risk-sharing schemes and issues
      involved in the actual implementation of such agreements.

PMID- 22991870
TI  - [The implementation of innovative medical technologies: biological
      pharmaceuticals for the treatment of psoriasis--a case study].
AB  - Advanced health systems worldwide strive to adopt new technologies that will
      ensure improved health and better clinical outcomes. The implementation of new
      medical technologies is affected by medical factors as well as economic and
      social forces, influencing both the individual and the health care providers.
      Chronic disease management is a major challenge to governments, as a result of
      the cumulative effects of chronic morbidity, life expectancy, quality of life and
      the national burden of disease due to accelerating medical expenditure.
      Psoriasis, a common chronic disease, for which advanced technologies were
      recently implemented, was chosen as a case study. The distribution of utility of
      various technologies for the treatment of psoriasis over the past nine years was
      analyzed to categorize "patterns of behavior" in accordance with the lifecycle of
      medical technology described in the Literature. It is expected that these
      changing trends will produce overall economic consequences, on direct expenditure
      combined with a reduction in some health services. Analyzing these clinical and
      economic trends, may add important considerations for the adoption of emerging
      medical technologies, presenting an important tool for policymakers at at all
      levels.

PMID- 22991871
TI  - [Will I be a good doctor?].

PMID- 22991872
TI  - [Root resection in the era of dental implants].
AB  - The treatment of furcation defects is one of the most challenging aspects of
      periodontal therapy. The periodontal therapist can utilize various treatment
      modalities, including: non surgical root debridement, local drug delivery, open
      flap surgery, tunneling, root resection, guided tissue regeneration and
      extraction. Each treatment method has its advantages and disadvantages. The
      dilemmas concerning tooth prognosis and prosthetic considerations in such cases
      are especially demanding, especially in comparison to implant therapy. The
      clinician's decision in these situations must comply with the objective condition
      in the particular case based on his abilities and knowledge and the patient
      expectations. In order to evaluate the relevancy of root resection procedures we
      reviewed the literature focusing on root resection therapy prognosis as well as
      the different therapeutic alternatives for furcated molar teeth. Root resection
      treatment guidelines, indications and contraindication are presented along with
      clinical examples. Root resection is currently a relevant treatment modality for
      furcation defects. By using proper case selection, good surgical technique,
      proper prosthetic treatment and good periodontal supportive care, a good 5 year
      prognosis can be achieved and complications can be minimized. In light of the
      growing literature concerning dental implants complications, extraction and
      dental implant placement should be recommended as the last option when all other
      conservative options cannot be used, or following their failure.

PMID- 22991873
TI  - [Current status of implant-abutment--part 1: abutments for cemented versus screw
      retained restorations].
AB  - Fixed implant supported single crowns and fixed dental prostheses (FDPs) have
      become an accepted treatment option for replacing and restoring missing teeth.
      Recent systematic reviews summarized excellent 5- and 10-year survival rates for
      both reconstruction types. In screw-retained restorations, the fastening screw
      provides a solid joint between the restoration and the implant abutment or
      between the restoration and the implant itself. With cement-retained prostheses,
      this restorative screw is eliminated for many reasons: esthetics, occlusal
      stability, and fabrication of passively fitting restorations. The purpose of this
      article is to review the variety of implant-abutments available for fabrication
      of fixed implant-supported restoration and compare between the various abutment
      forms (screw vs. cement retained).

PMID- 22991874
TI  - [Tooth color matching systems and communication with dental laboratory in
      indirect restorations: 2011 update].
AB  - There has been many technological developments in the last decade. Today's shade
      matching technologies have been developed in an effort to increase the success of
      color matching, communication, reproduction and verification in clinical
      dentistry and, ultimately, to increase the efficiency of esthetic restorative
      work within any practice. In general, the output of the color measurements can be
      classified and specified in several ways. The most common systems for describing
      color are Munsell's System and the international Commission on Illumination (CIE)
      L a b color system. Albert Munsell described color as a three-dimensional
      phenomenon. He described the three dimensions as hue, value (brightness), and
      chroma (saturation). Visual colour determination by comparison of teeth and shade
      guides is the most frequently applied method in dentistry. Vitapan Classical
      (Vita Zahnfabrik, Germany) and its derivations(evidence-based Vitapan 3D-Master
      shade guide and Linearguide) are the most commonly used shade guides. However,
      several factors can influence consistency of visual colour selection and
      specification: individual colour matching ability may vary, the colour perception
      of any individual may show temporal variation, the range of shades available is
      inadequate and does not cover the complete colour space of natural teeth, the
      shade guide tabs are not systematically distributed in their colour space, and
      changes in lighting conditions can cause alterations in perceived colour.
      instruments for clinical shade-matching encompass spectrophotometers,
      colorimeters and digital imaging systems. It can be concluded that different
      devices have different accuracy and precision. Colorimeters are significantly
      less reliable than spectrophotometers and digital cameras. Benefits and
      limitations exist, and the clinician must consider how the technology relates to
      expectations and needs. Combination of visual colour determination (Vitapan 3D
      Master shade guide and Linearguide) with digital cameras and electronic devices
      (spectrophotometers) increase chances for successful shade matching.

PMID- 22991875
TI  - [The inaccuracy of the panoramic radiograph as a tool to determine tooth
      inclination].
AB  - The panoramic radiograph is one of the most common radiographs in orthodontics.
      It is sometimes used as an aid for the decision which teeth should be extracted
      as part of the individual treatment plan. When treating patients with clear
      plates (for example, Invisalign), it is very important to know the inclination
      direction of the involved teeth. Tipping is more predictable and it takes less
      time than bodily movement. The objective of this paper is to demonstrate the
      limitations of the panoramic radiograph in the decision making process related
      extraction in orthodontics. An eleven years old girl with lower anterior crowding
      of about 5 mm was examined prior to her orthodontic treatment. One possible
      treatment plan, in order to relieve the crowding, was to extract two lower
      bicuspids. The other treatment plan was to extract one lower incisor. Clinically,
      both cuspids were acutely tipped mesially, but were imaged uprighted and parallel
      to their adjacent teeth in the panoramic radiograph. In order to better
      understand the cuspids position, a model of the lower arch was prepared, with a
      similar malocclusion demonstrated by the patient. In the model, the cuspids'
      metal teeth, invested in wax, were mesially angulated. A panoramic radiograph of
      the model was then taken. The radiograph of the model shows a parallel position
      of the incisors, the cuspids and the bicuspids, exactly as was shown in the
      patient's radiograph. It has been demonstrated that there is a discrepancy
      between the actual position of the teeth and roots and their position in the
      panoramic radiograph, especially in the mesiodistal angulation. It was concluded
      that we should be very cautious when trying to interpret the panoramic radiograph
      as a tool for root parallelism, and remember the inherent image distortions. This
      is especially true before deciding which teeth will be extracted, on the basis of
      "incorrect" tooth angulation.

PMID- 22991876
TI  - [The influence of dental implant surface on osseointegration: review].
AB  - Dental implant therapy is a prevalent and successful treatment, based on research
      and clinical experience. Ossointegration is the main factor that responsible for
      success or failure, initially of the implant, and in some cases followed with the
      whole treatment failure. The osseointegration process is influenced by several
      factors, among them the surface texture. Dental implants are available with
      different surface modifications that have been developed for enhancing clinical
      performances. This paper reviews the main treatments used for changing dental
      titanium implant surfaces, and compare the clinical performance of different
      types of implants. Based on existent literature, modified implant surface
      improves significantly the ability to achive optimise bone-implant contact and
      improve osseointegration. This review did not find any significant major
      differences between the surface modifications in use this days in terms of
      survival and success of specific implant. There are several methods that are no
      longer in use, due to poor clinical performance in the past.

PMID- 22991877
TI  - [Distance E-learning model for IDF dentists].
AB  - Distance E-learning is a novel educational modality, becoming more and more
      available in higher education facilities worldwide, as well as in the Israel
      Defense Forces, and its School of Military Medicine utilising the "Bareket" E
      Learning Interface. The use of distance E-learning is necessary due to the vast
      progress in medical research, and the need of every doctor for continuing
      education throughout his whole career. The School of Military Medicine is the
      main centre of medical knowledge in the IDF, and as such it has to address the
      need for continuing education, while allowing the doctors to continue their work
      at the field level without too many disturbances. Thus, we suggest the
      implementation of an E-learning system for field-level military dentists. The
      system is nowadays at its pilot run, and is successfully used by IDF dentists,
      allowing them to refreshen their knowledge on diagnosis and treatment of routine
      and emergency dental situations, to be examined and receive immediate feedback.
      Moreover, it allows the command level to control the whole learning process. The
      main goal of the proposed E-learning system is the standardization of the dental
      treatment given in field-level clinics throughout the IDF.

PMID- 22991878
TI  - A brief history of the dental drill.

PMID- 22991879
TI  - PAs' roles expected to expand under value-based purchasing.

PMID- 22991880
TI  - FDA limits acetaminophen; risk of death with tigecycline.

PMID- 22991881
TI  - Papules and plaques from head to foot. Pityriasis rubra pilaris.

PMID- 22991882
TI  - Sickle cell disease: What all PAs should know.

PMID- 22991883
TI  - Carpal tunnel syndrome: symptoms, diagnosis, and treatment options.

PMID- 22991884
TI  - Allergic reaction or food poisoning? The history holds the clue.

PMID- 22991885
TI  - Understanding DOT examinations for commercial vehicle drivers.

PMID- 22991886
TI  - PTSD-related sleep disturbances: is there evidence-based treatment?

PMID- 22991887
TI  - Medical and surgical management of peripheral arterial diseas.

PMID- 22991888
TI  - Lice infestations and scabies.

PMID- 22991889
TI  - Should I get the shingles vaccine?

PMID- 22991890
TI  - Patient information. Should I get the shingles vaccine?

PMID- 22991891
TI  - Eye pain and diplopia in a man kicked by a horse.

PMID- 22991892
TI  - What is your diagnosis? Mitral annulus calcification.

PMID- 22991893
TI  - Capillary coated with graphene and graphene oxide sheets as stationary phase for
      capillary electrochromatography and capillary liquid chromatography.
AB  - Graphene oxide (GO) nanosheets were immobilized onto the capillary wall using 3
      aminopropyldiethoxymethyl silane as coupling agent. Graphene coated column
      (G@column) was fabricated by hydrazine reduction of GO modified column. Scanning
      electron microscopy (SEM) images provided visible evidence of the GO grafted on
      the capillary wall. Energy dispersive X-ray spectrometry (EDS) indicated the high
      coverage of the GO on the capillary wall. The G@column exhibited a pH-dependent
      electroosmotic flow (EOF) from anode to cathode in the pH range of 3-9 while the
      graphene oxide coated column (GO@column) showed a constant EOF. Both GO@column
      and G@column were evaluated for open-tubular capillary electrochromatography (OT
      CEC). The GO@column was also evaluated for open-tubular capillary liquid
      chromatography (OT-CLC). Good separation of the tested neutral analytes on the
      GO@column was achieved on the basis of a typical reversed-phase behavior. On the
      contrary, G@column showed poor separation performance because of the strong pi-pi
      stacking and hydrophobic interactions between graphene and polyaromatic
      hydrocarbons. The high coverage of GO improved the column phase ratio which makes
      the GO@column promising for OT-CLC separation. Five of the major known proteins
      including three glycoisoforms of ovalbumin in chicken egg white were identified
      in a single run on the GO@column with phosphate buffer (5 mM, pH 7.0) and an
      applied voltage of 20 kV. The run-to-run, day-to-day, and column-to-column
      reproducibilities are evaluated by calculating the relative standard deviations
      (RSDs) of the EOF in OT-CEC and retention time of naphthalene in OT-CLC,
      respectively. These RSD values were found to be less than 3%.

PMID- 22991894
TI  - Ionically gelled alginate foams: physical properties controlled by operational
      and macromolecular parameters.
AB  - Alginates in the format of scaffolds provide important functions as materials for
      cell encapsulation, drug delivery, tissue engineering and wound healing among
      others. The method for preparation of alginate-based foams presented here is
      based on homogeneous, ionotropic gelation of aerated alginate solutions, followed
      by air drying. The method allows higher flexibility and better control of the
      pore structure, hydration properties and mechanical integrity compared to foams
      prepared by other techniques. The main variables for tailoring hydrogel
      properties include operational parameters such as degree of aeration and mixing
      times and concentration of alginate, as well as macromolecular properties such as
      the type of alginate (chemical composition and molecular weight distribution).
      Exposure of foams to gamma-irradiation resulted in a dose-dependent (0-30 kGy)
      reduction in molecular weight of the alginate and a corresponding reduction in
      tensile strength of the foams.

PMID- 22991896
TI  - Solution-cast metal oxide thin film electrocatalysts for oxygen evolution.
AB  - Water oxidation is a critical step in water splitting to make hydrogen fuel. We
      report the solution synthesis, structural/compositional characterization, and
      oxygen evolution reaction (OER) electrocatalytic properties of ~2-3 nm thick
      films of NiO(x), CoO(x), Ni(y)Co(1-y)O(x), Ni(0.9)Fe(0.1)O(x), IrO(x), MnO(x),
      and FeO(x). The thin-film geometry enables the use of quartz crystal
      microgravimetry, voltammetry, and steady-state Tafel measurements to study the
      electrocatalytic activity and electrochemical properties of the oxides.
      Ni(0.9)Fe(0.1)O(x) was found to be the most active water oxidation catalyst in
      basic media, passing 10 mA cm(-2) at an overpotential of 336 mV with a Tafel
      slope of 30 mV dec(-1) with oxygen evolution reaction (OER) activity roughly an
      order of magnitude higher than IrO(x) control films and similar to the best known
      OER catalysts in basic media. The high activity is attributed to the in situ
      formation of layered Ni(0.9)Fe(0.1)OOH oxyhydroxide species with nearly every Ni
      atom electrochemically active. In contrast to previous reports that showed
      synergy between Co and Ni oxides for OER catalysis, Ni(y)Co(1-y)O(x) thin films
      showed decreasing activity relative to the pure NiO(x) films with increasing Co
      content. This finding is explained by the suppressed in situ formation of the
      active layered oxyhydroxide with increasing Co. The high OER activity and simple
      synthesis make these Ni-based catalyst thin films useful for incorporating with
      semiconductor photoelectrodes for direct solar-driven water splitting or in high
      surface-area electrodes for water electrolysis.

PMID- 22991895
TI  - Structural basis of functional group activation by sulfotransferases in complex
      metabolic pathways.
AB  - Sulfated molecules with diverse functions are common in biology, but sulfonation
      as a method to activate a metabolite for chemical catalysis is rare. Catalytic
      activity was characterized and crystal structures were determined for two such
      "activating" sulfotransferases (STs) that sulfonate beta-hydroxyacyl thioester
      substrates. The CurM polyketide synthase (PKS) ST domain from the curacin A
      biosynthetic pathway of Moorea producens and the olefin synthase (OLS) ST from a
      hydrocarbon-producing system of Synechococcus PCC 7002 both occur as a unique
      acyl carrier protein (ACP), ST, and thioesterase (TE) tridomain within a larger
      polypeptide. During pathway termination, these cyanobacterial systems introduce a
      terminal double bond into the beta-hydroxyacyl-ACP-linked substrate by the
      combined action of the ST and TE. Under in vitro conditions, CurM PKS ST and OLS
      ST acted on beta-hydroxy fatty acyl-ACP substrates; however, OLS ST was not
      reactive toward analogues of the natural PKS ST substrate bearing a C5-methoxy
      substituent. The crystal structures of CurM ST and OLS ST revealed that they are
      members of a distinct protein family relative to other prokaryotic and eukaryotic
      sulfotransferases. A common binding site for the sulfonate donor 3'
      phosphoadenosine-5'-phosphosulfate was visualized in complexes with the product
      3'-phosphoadenosine-5'-phosphate. Critical functions for several conserved amino
      acids in the active site were confirmed by site-directed mutagenesis, including a
      proposed glutamate catalytic base. A dynamic active-site flap unique to the
      "activating" ST family affects substrate selectivity and product formation, based
      on the activities of chimeras of the PKS and OLS STs with exchanged active-site
      flaps.

PMID- 22991897
TI  - My last issue.

PMID- 22991898
TI  - Rationing time.

PMID- 22991899
TI  - Managing referrals and referral specialists.

PMID- 22991900
TI  - Managing referrals and referral specialists.

PMID- 22991901
TI  - Medicare annual wellness visit health risk assessment.

PMID- 22991902
TI  - "Heartsink" patients.

PMID- 22991903
TI  - Clarification.

PMID- 22991904
TI  - Making Medicare annual wellness visits work in practice.

PMID- 22991905
TI  - Direct-to-consumer marketing of durable medical equipment.

PMID- 22991906
TI  - A toolkit to improve the treatment of CA-MRSA.

PMID- 22991907
TI  - Managing messages.

PMID- 22991916
TI  - Five reactions to a new EHR.

PMID- 22991917
TI  - Protein-mediated synthesis of nanosized Mn-doped ZnS: a multifunctional, UV
      durable bio-nanocomposite.
AB  - The design of synthetic nanoparticles (NPs) capable of recognizing given chemical
      entities in a specific and predictable manner is of great fundamental and
      practical importance. Herein, we report a simple, fast, water-soluble, and green
      phosphine free colloidal synthesis route for the preparation of multifunctional
      enzyme-capped ZnS bionanocomposites (BNCs) with/without transitional metal-ion
      doping. The enzymes alpha-Chymotrypsin (CHT), associated with the NPs, are
      demonstrated as an effectual host for organic dye Methylene Blue (MB) revealing
      the molecular recognition of such dye molecules by the BNCs. An effective hosting
      of MB in the close proximity of ZnS NPs (with ~3 nm size) leads to photocatalysis
      of the dyes which has further been investigated with doped-semiconductors. The NP
      associated enzyme alpha-CHT is found to be active toward a substrate (Ala-Ala-Phe
      7-amido-4-methyl-coumarin), hence leads to significant enzyme catalysis.
      Irradiation induced luminescence enhancement (IILE) measurements on the BNCs
      clearly interpret the role of surface capping agents which protect against deep
      UV damaging of ZnS NPs.

PMID- 22991918
TI  - Palladium(II)-catalyzed tandem cyclization/C-H functionalization of alkynes for
      the synthesis of functionalized indoles.
AB  - A palladium-catalyzed tandem cyclization/C-H functionalization of two alkynes was
      accomplished to construct a series of polycyclic functionalized indoles. A range
      of internal alkynes bearing synthetically useful functional groups were
      tolerated. A good regioselectivity was observed when alkyl-substituted alkynes
      were introduced into the reaction system, and a single product was obtained.
      Molecular oxygen was used as the terminal oxidant in the approach, rendering the
      reaction more sustainable.

PMID- 22991919
TI  - Pegfilgrastim administered in an abbreviated schedule, significantly improved
      neutrophil recovery after high-dose radiation-induced myelosuppression in rhesus
      macaques.
AB  - Conventional daily administration of filgrastim is effective in reducing the
      duration of severe neutropenia and enhancing survival following lethal radiation,
      myelosuppressive cytotoxic therapy or myeloablation and stem cell
      transplantation. A sustained-duration form of filgrastim, pegfilgrastim has
      significantly simplified scheduling protocols after chemotherapy-induced
      neutropenia to a single injection while maintaining the therapeutic effectiveness
      of daily administration of filgrastim. We examined the ability of a single or
      double (weekly) administration of pegfilgrastim to significantly improve
      neutrophil recovery in a rhesus macaque model of severe radiation-induced
      myelosuppression. Animals were exposed to potentially lethal 6 Gy total-body X
      radiation. After irradiation all animals received supportive care and were
      administered either pegfilgrastim at 300 MUg/kg on day 1 or day 1 and day 7 post
      exposure, or filgrastim at 10 MUg/kg/day initiated on day 1 post exposure and
      continued daily through neutrophil recovery. Pharmacokinetic parameters and
      neutrophil-related values for duration of neutropenia, neutrophil nadir, time to
      recovery to an absolute neutrophil count >=500/MUL or >=2000/MUL, and days of
      antibiotic support were determined. Effective plasma concentrations of
      pegfilgrastim were maintained in neutropenic animals until after the onset of
      hematopoietic recovery, which is consistent with neutrophil-dependent properties
      of elimination. Administration of pegfilgrastim at day 1 and day 7 was most
      effective at improving neutrophil recovery compared to daily administration of
      filgrastim or a single injection of pegfilgrastim on day 1, after severe,
      radiation-induced myelosuppression in rhesus macaques.

PMID- 22991920
TI  - Corrosion stability and bioactivity in simulated body fluid of
      silver/hydroxyapatite and silver/hydroxyapatite/lignin coatings on titanium
      obtained by electrophoretic deposition.
AB  - Hydroxyapatite is the most suitable biocompatible material for bone implant
      coatings. However, its brittleness is a major obstacle, and that is why,
      recently, research focused on creating composites with various biopolymers. In
      this study, hydroxyapatite coatings were modified with lignin in order to attain
      corrosion stability and surface porosity that enables osteogenesis. Incorporating
      silver, well known for its antimicrobial properties, seemed the best strategy for
      avoiding possible infections. The silver/hydroxyapatite (Ag/HAP) and
      silver/hydroxyapatite/lignin (Ag/HAP/Lig) coatings were cathaphoretically
      deposited on titanium from ethanol suspensions, sintered at 900  degrees C in Ar,
      and characterized by X-ray diffraction, scanning electron microscopy, field
      emission scanning electron microscopy, attenuated total reflection Fourier
      transform infrared, and X-ray photoelectron spectroscopy. The corrosion stability
      of electrodeposited coatings was evaluated in vitro in Kokubo's simulated body
      fluid (SBF) at 37  degrees C using electrochemical impedance spectroscopy.
      Bioactivity was estimated by immersion in SBF to evaluate the formation of
      hydroxyapatite on the coating surface. A microcrystalline structure of newly
      formed plate-shaped carbonate-hydroxyapatite was detected after only 7 days,
      indicating enhanced bioactive behavior. Both coatings had good corrosion
      stability during a prolonged immersion time. Among the two, the Ag/HAP/Lig
      coating had a homogeneous surface, less roughness, and low values of contact
      angle.

PMID- 22991921
TI  - Raising the thermoelectric performance of p-type PbS with endotaxial
      nanostructuring and valence-band offset engineering using CdS and ZnS.
AB  - We have investigated in detail the effect of CdS and ZnS as second phases on the
      thermoelectric properties of p-type PbS. We report a ZT of ~1.3 at 923 K for 2.5
      at.% Na-doped p-type PbS with endotaxially nanostructured 3.0 at.% CdS. We
      attribute the high ZT to the combination of broad-based phonon scattering on
      multiple length scales to reduce (lattice) thermal conductivity and favorable
      charge transport through coherent interfaces between the PbS matrix and metal
      sulfide nanophase precipitates, which maintains the requisite high carrier
      conductivity and the associated power factor. Similar to large ionically bonded
      metal sulfides (ZnS, CaS, and SrS), the covalently bonded CdS can also
      effectively reduce the lattice thermal conductivity in p-type PbS. The presence
      of ubiquitous nanostructuring was confirmed by transmission electron microscopy.
      Valence and conduction band energy levels of the NaCl-type metal sulfides, MS (M
      = Pb, Cd, Zn, Ca, and Sr) were calculated from density functional theory to gain
      insight into the band alignment between PbS and the second phases in these
      materials. The hole transport is controlled by band offset minimization through
      the alignment of valence bands between the host PbS and the embedded second
      phases, MS (M = Cd, Zn, Ca, and Sr). The smallest valence band offset of about
      0.13 eV at 0 K was found between PbS and CdS which is diminished further by
      thermal band broadening at elevated temperature. This allows carrier transport
      between the endotaxially aligned components (i.e., matrix and nanostructure),
      thus minimizing significant deterioration of the hole mobility and power factor.
      We conclude the thermoelectric performance of the PbS system and, by extension,
      other systems can be enhanced by means of a closely coupled phonon
      blocking/electron-transmitting approach through embedding endotaxially
      nanostructured second phases.

PMID- 22991922
TI  - New ruthenium(II)-letrozole complexes as anticancer therapeutics.
AB  - Novel ruthenium-letrozole complexes have been prepared, and cell viability of two
      human cancer cell types (breast and glioblastoma) was determined. Some ruthenium
      compounds are known for their cytotoxicity to cancer cells, whereas letrozole is
      an aromatase inhibitor administered after surgery to post-menopausal women with
      hormonally responsive breast cancer. A significant in vitro activity was
      established for complex 5.Let against breast cancer MCF-7 cells and significantly
      lower activity against glioblastoma U251N cells. The activity of 5.Let was even
      higher than that of 4, a compound analogous to the well-known drug RAPTA-C.
      Results from the combination of 5.Let (or 4) with 3-methyladenine (3-MA) or with
      curcumin, respectively, revealed that the resultant cancer cell death likely
      involves 5.Let-induced autophagy.

PMID- 22991924
TI  - Organocatalytic one-pot oxidative cleavage of terminal diols to dehomologated
      carboxylic acids.
AB  - The organocatalytic one-pot oxidative cleavage of terminal 1,2-diols to one
      carbon-unit-shorter carboxylic acids is described. The combination of 1-Me-AZADO
      (cat.), NaOCl (cat.), and NaClO(2) caused smooth one-pot oxidative cleavage under
      mild conditions. A broad range of substrates including carbohydrates and N
      protected amino diols were converted without epimerization. Terminal triols and
      tetraols respectively underwent cleavage of their C-2 and C-3 moieties to afford
      their corresponding two- and three-carbon-unit-shorter carboxylic acids.

PMID- 22991923
TI  - Incidence of renal toxicity in HIV-infected, antiretroviral-naive patients
      starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir,
      or lopinavir/ritonavir.
AB  - OBJECTIVES: We performed a retrospective cohort study of HIV-infected
      antiretroviral-naive patients starting a first antiretroviral therapy with
      tenofovir/emtricitabine plus efavirenz (EFV), atazanavir/ritonavir (ATV/r), or
      lopinavir/ritonavir (LPV/r). METHODS: The incidence of renal impairment or
      proximal tubular dysfunction was evaluated during a 12-month follow-up. Renal
      impairment was diagnosed by a reduced estimated glomerular filtration rate (eGFR)
      calculated using the Modification of Diet in Renal Disease (MDRD) formula, and
      tubular dysfunction was diagnosed when >= 2 among proteinuria, glucosuria,
      hypouricaemia, hypophosphataemia, and hypokalaemia, were identified. RESULTS: A
      total of 235 patients were enrolled: 82 taking EFV, 78 ATV/r, and 75 LPV/r. The
      mean decline in eGFR after the 12-month follow-up was significantly greater in
      subjects treated with ATV/r (-10.4 ml/min/1.73 m(2)) than in those receiving EFV
      (- 5.1; p = 0.002) or LPV/r (-4.8; p = 0.003). Similarly, a significantly higher
      incidence of proximal tubulopathy was observed among ATV/r-treated patients
      (14.1%) compared with patients receiving EFV (4.9%) or LPV/r (5.3%). CONCLUSIONS:
      In our retrospective study, naive patients receiving tenofovir/emtricitabine and
      ATV/r for 12 months showed a significantly higher decline in eGFR and a
      significantly higher incidence of proximal tubulopathy than those receiving
      tenofovir/emtricitabine plus EFV or LPV/r, even though clinically evident renal
      toxicity associated with tenofovir-based treatment is a very uncommon event.

PMID- 22991925
TI  - Expression of prostanoid receptors (EP1, 2, 3, and 4) in normal and methimazole
      treated mouse olfactory epithelium.
AB  - CONCLUSION: Prostanoid receptors (EP1, EP2, EP3, and EP4) are expressed in the
      olfactory epithelium (OE), and the EP4 prostanoid receptor may play an important
      role in the OE. OBJECTIVE: The purpose of the present study was to investigate
      the expression and localization of the four types of prostanoid receptors (EP1,
      EP2, EP3, and EP4) in the OE of normal and methimazole-treated mice to gain more
      complete knowledge about the functional significance of the prostanoid receptors
      in OE. METHODS: CBA/J mice were used in this study. The localization of the
      prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE was investigated by
      immunohistochemistry. The changes in expression of prostanoid receptors were
      studied in methimazole-treated mice. Furthermore, the effect of EP agonists on
      the methimazole-induced degeneration of OE was assessed by morphological analysis
      and by assessment of apoptosis. RESULTS: All four types of EP receptors were
      recognized in mouse OE. Expression of EP4 in the OE was significantly reduced
      after methimazole treatment. In the methimazole-treated mice, an EP4 agonist
      reduced OE damage and apoptosis.

PMID- 22991926
TI  - Retinal function and morphology in central retinal vein occlusion with macular
      edema.
AB  - PURPOSE/AIM: To investigate the relations among best-corrected visual acuity
      (BCVA), macular sensitivity, macular thickness, and macular volume in patients
      with central retinal vein occlusion (CRVO) and macular edema. MATERIALS AND
      METHODS: In 16 consecutive patients with CRVO (mean age: 71.9 +/- 6.9 years; 10
      women and six men), macular function was documented by microperimetry and BCVA
      was determined on the logarithm of the minimum angle of resolution scale. Macular
      thickness and macular volume were measured by optical coherence tomography (OCT),
      and mean macular sensitivity was calculated for each of nine macular subfields on
      the retinal map obtained by OCT. RESULTS: BCVA was correlated with both macular
      thickness and macular volume in all nine subfields of the macular region. In
      contrast, macular sensitivity was correlated with both macular thickness and
      macular volume in six out of nine subfields (superior inner, superior outer,
      inferior inner, inferior outer, nasal inner, and nasal outer). The correlations
      were stronger in the nasal subfields than the other subfields. CONCLUSIONS: These
      findings suggest that evaluation of both visual acuity and macular sensitivity
      might be important when assessing visual function in CRVO patients with macular
      edema.

PMID- 22991927
TI  - JAK2 inhibitors in the treatment of myeloproliferative neoplasms.
AB  - INTRODUCTION: Dysregulation of JAK-STAT signaling is a pathogenetic hallmark of
      myeloproliferative neoplasms (MPNs) arising from several distinct molecular
      aberrations, including mutations in JAK2, the thrombopoietin receptor (MPL),
      mutations in negative regulators of JAK-STAT signaling, such as lymphocyte
      specific adapter protein (SH2B3), and epigenetic dysregulation as seen with
      Suppressor of Cytokine Signaling (SOCS) proteins. In addition, growth
      factor/cytokine stimulatory events activate JAK-STAT signaling independent of
      mutations. AREAS COVERED: The various mutations and molecular events activating
      JAK-STAT signaling in MPNs are reviewed. Detailed inhibitory kinase profiles of
      the currently developed JAK inhibitors are presented. Clinical trial results for
      currently developed JAK targeting agents are comprehensively summarized. The
      limitations of JAK-STAT targeting in MPNs, as well as potential rational
      combination therapies with JAK2 inhibitors, are discussed. EXPERT OPINION:
      Aberrant JAK-STAT signaling is an underlying theme in the pathogenesis of MPNs.
      While JAK2 inhibitors are active in JAK2V617F and wild-type JAK2 MPNs, JAK2V617F
      mutation-specific or JAK2-selective inhibitors may possess unique clinical
      attributes. Complimentary targeting of parallel pathways operating in MPNs may
      offer novel therapeutic approaches in combination with JAK inhibition.
      Understanding the intricacies of JAK-STAT pathway activation, including growth
      factor/cytokine-driven signaling, will open new avenues for therapeutic
      intervention at known and novel molecular vulnerabilities of MPNs.

PMID- 22991928
TI  - Fatty acids in breast milk associated with asthma-like symptoms and atopy in
      infancy: a longitudinal study.
AB  - OBJECTIVE: The relationship between fatty acids (FAs) in breast milk and the risk
      of childhood allergies is controversial. We prospectively investigated the
      relationship between FAs in colostrum and breast milk and asthma-like symptoms
      (AS) and atopy in infancy. METHODS: Pregnant women were recruited in Columbia and
      Charleston, South Carolina. Colostrum and mature milk samples were collected. The
      concentrations of n-3 FAs (eicosapentaenoic acid, alpha-linolenic acid,
      docosapentaenoic acid, and docosahexaenoic acid) and n-6 FAs (linoleic acid,
      arachidonic acid, and eicosadienoic acid) were determined by gas chromatography.
      AS were ascertained at 6 and 12 months of age and atopy (skin prick test) at 12
      months. FAs were dichotomized (high vs. median and low). Generalized estimating
      equations were used to determine the effect of FAs on repeated AS, compensating
      for intra-individual correlations and adjusting for confounders. Log-linear
      regression was used to analyze atopy. RESULTS: FAs were analyzed in 24 colostrum
      and 78 breast milk samples. High levels of total n-6 (lipid based) FAs in breast
      milk were associated with an increased risk of AS in infants (risk ratio (RR) =
      2.91; 95% confidence interval (CI): 1.37, 6.18), even after controlling for total
      n-3 FAs (RR = 2.07, 95% CI: 1.12, 3.85). High levels of total n-3 FAs controlling
      for n-6 FAs decreased the risk of atopy at the age of 12 months. CONCLUSIONS:
      High levels of total n-6 polyunsaturated fatty acids (PUFAs) in breast milk are
      associated with an increased risk for AS, whereas high levels of total n-3 PUFAs
      decreased the risk of atopy. These data suggest that the effects of n-3 and n-6
      PUFAs on allergic disorders should be further explored.

PMID- 22991929
TI  - Micropatterning of hydrogels on locally hydrophilized regions on PDMS by stepwise
      solution dipping and in situ gelation.
AB  - This study presents a simple but highly versatile method of fabricating picoliter
      volume hydrogel patterns on poly(dimethylsiloxane) (PDMS) substrates. Hydrophilic
      regions were prepared on hydrophobic PDMS plates by trapping and melting
      functional polymer particles and performing subsequent reactions with partially
      oxidized dextran. Small aliquots of a gelation solution were selectively trapped
      on the hydrophilic areas by a simple dipping process that was utilized to make
      thin hydrogel patterns by the in situ gelation of a sol solution. Using this
      process, we successfully formed calcium alginate, collagen I, and chitosan
      hydrogels with a thickness of several micrometers and shapes that followed the
      hydrophilized regions. In addition, alginate and collagen gel patterns were used
      to capture cells with different adhesion properties selectively on or off the
      hydrogel structures. The presented strategy could be applicable to the
      preparation of a variety of hydrogels for the development of functional
      biosensors, bioreactors, and cell cultivation platforms.

PMID- 22991930
TI  - Plant asparaginase-based asparagine biosensor for leukemia.
AB  - The present work aims at the development of plant asparaginase-based asparagine
      biosensor for leukemia. It is a novel diagnostic for monitoring asparagine levels
      in patients suffering from acute lymphoblastic leukemia (ALL). Various
      immobilization strategies have been applied to improve the stability of the
      asparaginase. The latest and updated information including some new techniques of
      immobilization related to L-asparaginase such as gelatin, agarose, agar, and
      calcium alginate methods are described in detail along with response time studies
      and comparative data. Furthermore these immobilization techniques have been
      applied for the detection of asparagine in normal and leukemia serum samples.

PMID- 22991931
TI  - 'I think it's about experiencing, like, life': a qualitative exploration of
      contemporary adolescent intimate relationships in South Africa.
AB  - Intimate or dating relationships play an important role in young people's
      psychosocial development and well-being. Yet, we know relatively little about how
      teenagers conceptualise and experience them. Research knowledge about young
      people's intimate relationships is largely gleaned from studies whose primary
      focus has been on adolescent sexuality and violence. This study explored intimate
      relationships using qualitative data from 12 focus-group discussions and 25 in
      depth individual interviews with Grade 8 (mean age = 14.6 years) and Grade 11
      (mean age = 17.2 years) young people recruited from Cape Town schools. Although
      there is overlap between these findings and previous research, this study delved
      into the microdynamics of teenagers' relationship practices and
      conceptualisations. Their discussions provide insight into a nebulous dating
      landscape that is highly gendered and greatly influenced by peer relations. There
      was a heterogeneity of experience with relationships and sex. Implications for
      intervention development are discussed.

PMID- 22991932
TI  - Multiple and different genomic rearrangements of the rbcL gene are present in the
      parasitic orchid Neottia nidus-avis.
AB  - In parasitic plants that have lost most, if not all, of their photosynthetic
      genes, the genome of their plastids has also undergone a dramatic reduction. For
      example, photosynthetic genes, such as rbcL, frequently become pseudogenes, in
      which large portions of the gene have been found to be deleted. Orchids are
      flowering plants with several parasitic lineages. This is consistent with the
      observation that parasitic orchids can invade pre-existing mutualistic
      associations between ectomycorrhizal trees and fungi to obtain fixed carbon and
      nutrients. In addition, some parasitic species are devoid of chlorophyll, and
      consequently, have lost their photosynthetic capacity. Here, the organization of
      the plastid genome of the parasitic orchid  Neottia nidus-avis  (L.) Rich. was
      investigated using sequencing and hybridization experiments. In particular,
      genomic rearrangements in the rbcL region of this parasitic orchid were analyzed.
      At least three distinct rbcL sequences were found to be present as pseudogenes
      and were likely located in the plastid genome. Based on these results, it is
      hypothesized that N. nidus-avis contains different plastomes, each with a
      different pseudogene, and these can exist within the same individual plant.

PMID- 22991933
TI  - EDTA chelation reappraisal following new clinical trials and regular use in
      millions of patients: review of preliminary findings and risk/benefit assessment.
AB  - EDTA chelation therapy is regularly used in thousands of patients worldwide. An
      FDA approval of more than 50 years ago for heavy metal detoxification prompted
      many physicians to use EDTA as an alternative medicine for many categories of
      patients. Recently, NIH initiated the so-called Trial to Assess Chelation Therapy
      (TACT), which has been designed to evaluate whether EDTA and high dose oral
      vitamins and mineral therapy could offer clinical, quality of life, and economic
      benefits for patients with a previous myocardial infraction. A 50% reduction of
      urinary Pb and improvement of systolic blood pressure was observed in 33
      cardiovascular patients following 20 iv administrations. In another study
      involving 15 patients of different categories, EDTA also has been shown to be an
      effective and nontoxic chelator for the removal of xenobiotic metals such as Pb,
      Cd, Ni and Al. Administration of iv EDTA on weekly basis appears to be a
      sufficient and nontoxic protocol for treating patients with suspected overload
      and toxicity of xenobiotic metals especially Pb and Cd. The causative effect of
      xenobiotic metals in cancer, cardiovascular, neurodegenerative, renal and other
      diseases needs further investigation. Similarly, the use of EDTA chelation
      therapy in other conditions, which are not related to xenobiotic metal toxicity
      needs further investigation and confirmation of therapeutic use from controlled
      randomized clinical trials. Metal balance and drug interaction studies are
      required to clarify the risk/benefit assessment for the long term use of EDTA in
      patients with excess xenobiotic metal toxicity and in other conditions.

PMID- 22991934
TI  - Motivational interviewing: a novel intervention for translating rehabilitation
      research into practice.
AB  - PURPOSE: Despite recent advances in rehabilitation research, moving evidence into
      clinical practice remains a challenge. This article explores a novel approach to
      knowledge translation (KT) - motivational interviewing (MI). MI is a style of
      communication that is typically used to facilitate health related behavior change
      in patients. Here we explore its potential use as a KT intervention aimed at
      clinicians. METHODS: Commentary. Relevant literature on MI and KT is summarized
      and discussed by considering how MI could be used in a KT strategy aimed at
      rehabilitation clinicians. RESULTS: Clinician motivation and readiness to change
      are key issues influencing implementation of evidence-based practice. We provide
      an argument suggesting that clinicians' readiness to change clinical practices
      can potentially be enhanced through MI. The MI conceptual framework, principles,
      and strategies, typically used in patients, are discussed here in a novel context
      - enhancing clinician change in practice. CONCLUSIONS: MI is an effective
      intervention when the goal is to motivate individuals to change a current
      behavior. We suggest that MI is an evidence-based intervention that has been
      proven to be effective with patients and warrants study as a promising KT
      intervention. IMPLICATIONS FOR REHABILITATION: * Despite recent advances in
      rehabilitation research, moving evidence into practice remains a challenge. *
      Clinician motivation is one key issue influencing the implementation of evidence
      based practice. * Clinician motivation to implement evidence-based practice can
      potentially be enhanced through an approach called motivational interviewing
      (MI). * Motivational interviewing is an evidence-based intervention that has
      proven to be effective in promoting behavioral change in patients, and warrants
      study in terms of its potential as a KT intervention.

PMID- 22991935
TI  - Neurocognitive performance of a community-based sample of young people at
      putative ultra high risk for psychosis: support for the processing speed
      hypothesis.
AB  - INTRODUCTION: A wide variety of neurocognitive deficits have been reported for
      help-seeking individuals who are at clinical or ultra high risk for psychosis
      based on fulfilling set criteria for prodromal syndromes/at risk mental states.
      We wished to extend this research by conducting the first population-based
      assessment of prodromal syndromes and associated neurocognition. METHODS: A
      sample of 212 school-based adolescents were assessed for prodromal syndromes
      using the criteria of prodromal syndromes from the Structured Interview for
      Prodromal Syndromes. The MATRICS consensus neurocognitive battery was used to
      assess cognitive functioning in this sample. RESULTS: A total of 8% of the
      population sample of adolescents met criteria for a prodromal syndrome. These
      adolescents performed significantly more poorly than controls on two tests of
      processing speed-Trail-Making Test Part A, F=4.54, p < .01, and the Brief
      Assessment of Cognition in Schizophrenia Symbol Coding task, F=8.26, p < .0001
      and on a test of nonverbal working memory-the Wechsler Memory Scale Spatial Span
      task, F=3.29, p < .05. CONCLUSIONS: Adolescents in the community who fulfil
      criteria for prodromal syndromes demonstrate deficits on a number of
      neurocognitive tasks. Deficits are particularly pronounced in symbol coding
      performance, supporting processing speed as a central deficit associated with
      psychosis risk.

PMID- 22991936
TI  - Bacteriophage virion-associated peptidoglycan hydrolases: potential new
      enzybiotics.
AB  - Virion-associated peptidoglycan hydrolases (VAPGH) are phage-encoded lytic
      enzymes that locally degrade the peptidoglycan (PG) of the bacterial cell wall
      during infection. In contrast to endolysins, PGHs that mediate lysis of the host
      bacteria at the end of the lytic cycle to release of phage progeny, the action of
      VAPGHs generates a small hole through which the phage tail tube crosses the cell
      envelope to eject the phage genetic material at the beginning to the infection
      cycle. The antimicrobial activity of VAPGHs was first discovered through the
      observation of the phenomenon of 'lysis from without', in which the disruption of
      the bacterial cell wall occurs prior to phage production and is caused by a high
      number of phages adsorbed onto the cell surface. Based on a unique combination of
      properties of VAPGHs such as high specificity, remarkable thermostability, and a
      modular organization, these proteins are potential candidates as new
      antibacterial agents, e.g. against antibiotic-resistant bacteria in human therapy
      and veterinary as well as biopreservatives in food safety, and as biocontrol
      agents of harmful bacteria in agriculture. This review provides an overview of
      the different VAPGHs discovered to date and their potential as novel
      antimicrobials. 

PMID- 22991937
TI  - Cellulose-nanofiber-reinforced poly(lactic acid) composites prepared by a water
      based approach.
AB  - The difficulty of dispersing cellulose nanofibers (CNFs) in hydrophobic polymers
      such as poly(lactic acid) (PLA) remains a major obstacle to the expansion of
      cellulose nanocomposite applications. In this work, we employed the solvent
      evaporation technique commonly used for drug microencapsulation to suspend PLA in
      water as microparticles. The suspension of the microparticles was easily mixed
      with the CNFs prepared by high-pressure homogenization. Water removal by membrane
      filtration produced CNF sheets filled with the particles. Compression molding of
      the stacked sheets resulted in nanocomposites with good CNF dispersions.
      Increases in the modulus and strength (up to 58% and 210%, respectively)
      demonstrated the load-bearing capability of the CNF network in the composites.

PMID- 22991938
TI  - Volatile organic compounds of lung cancer and possible biochemical pathways.

PMID- 22991940
TI  - Label-free mapping of osteopontin adsorption to calcium oxalate monohydrate
      crystals by tip-enhanced Raman spectroscopy.
AB  - In the ectopic biomineralization of calcium oxalate kidney stones, the
      competition between calcium oxalate monohydrate (COM) formation and its
      inhibition by the phosphoprotein osteopontin (OPN) plays a key role in COM stone
      forming processes. To get more insights into these processes, tip-enhanced Raman
      spectroscopy (TERS) was used to provide surface-specific information about the
      adsorption of OPN to faces of COM crystals. In TERS, the surface plasmon
      resonance of a metallic AFM tip is locally excited when the tip is placed in the
      optical near-field of a laser focused on the crystal surface. Excitation of this
      localized surface plasmon resonance allows the enhancement of the Raman signal as
      well as the improvement of the spatial resolution beyond the diffraction limit of
      the light. As TERS works label free and noninvasively, it is an excellent
      technique to study the distribution of adsorbed proteins on crystal faces at the
      submicrometer scale. In the present work, we generated Raman intensity maps
      indicating high spatial resolution and a distinct variation in relative peak
      intensities. The collected TERS spectra show that the OPN preferentially adsorbs
      to edges and faces at the ends of COM crystals (order: {100}/{121} edge > {100}
      face > {100}/{010} edge ~ {121}/{010} edge > {010} face) providing also relevant
      information on the inhibition of crystal growth. This study demonstrates that
      TERS is an excellent technique for detailed investigations of biomolecules
      adsorbed, layered, or assembled to a large variety of surfaces and interfaces.

PMID- 22991941
TI  - Divergent synthesis of benzene derivatives: Bronsted acid catalyzed and iodine
      promoted tandem cyclization of 5,2-enyn-1-ones.
AB  - Highly substituted benzene derivatives, including alkoxy-, iodoalkoxy-, and
      diiodo-substituted benzenes, can be selectively synthesized via Bronsted acid
      catalyzed and iodine-promoted tandem carbocyclization respectively. This reaction
      involved a direct process for C-C bond formation from 5,2-enyn-1-ones, and
      different reaction systems (Bronsted acids/electrophiles with solvents) afforded
      different substituted benzenes. Furthermore, the halogenated moiety and alkoxy
      group can be readily introduced into the benzene in a position which has not been
      easily obtained previously.

PMID- 22991939
TI  - Trigonal Mn3 and Co3 clusters supported by weak-field ligands: a structural,
      spectroscopic, magnetic, and computational investigation into the correlation of
      molecular and electronic structure.
AB  - Transamination of divalent transition metal starting materials
      (M(2)(N(SiMe(3))(2))(4), M = Mn, Co) with hexadentate ligand platforms (R)LH(6)
      ((R)LH(6) = MeC(CH(2)NPh-o-NR)(3) where R = H, Ph, Mes (Mes = Mesityl)) or
      (H,Cy)LH(6) = 1,3,5-C(6)H(9)(NHPh-o-NH(2))(3) with added pyridine or tertiary
      phosphine coligands afforded trinuclear complexes of the type ((R)L)Mn(3)(py)(3)
      and ((R)L)Co(3)(PMe(2)R')(3) (R' = Me, Ph). While the sterically less encumbered
      ligand varieties, (H)L or (Ph)L, give rise to local square-pyramidal geometries
      at each of the bound metal atoms, with four anilides forming an equatorial plane
      and an exogenous pyridine or phosphine in the apical site, the mesityl
      substituted ligand ((Mes)L) engenders local tetrahedral coordination. Both the
      neutral Mn(3) and Co(3) clusters feature S = (1)/(2) ground states, as determined
      by direct current (dc) magnetometry, (1)H NMR spectroscopy, and low-temperature
      electron paramagnetic resonance (EPR) spectroscopy. Within the Mn(3) clusters,
      the long internuclear Mn-Mn separations suggest minimal direct metal-metal
      orbital overlap. Accordingly, fits to variable-temperature magnetic
      susceptibility data reveal the presence of weak antiferromagnetic superexchange
      interactions through the bridging anilide ligands with exchange couplings ranging
      from J = -16.8 to -42 cm(-1). Conversely, the short Co-Co interatomic distances
      suggest a significant degree of direct metal-metal orbital overlap, akin to the
      related Fe(3) clusters. With the Co(3) series, the S = (1)/(2) ground state can
      be attributed to population of a single molecular orbital manifold that arises
      from mixing of the metal- and o-phenylenediamide (OPDA) ligand-based frontier
      orbitals. Chemical oxidation of the neutral Co(3) clusters affords diamagnetic
      cationic clusters of the type [((R)L)Co(3)(PMe(2)R)(3)](+). Density functional
      theory (DFT) calculations on the neutral (S = (1)/(2)) and cationic (S = 0) Co(3)
      clusters reveal that oxidation occurs at an orbital with contributions from both
      the Co3 core and OPDA subunits. The predicted bond elongations within the ligand
      OPDA units are corroborated by the ligand bond perturbations observed by X-ray
      crystallography.

PMID- 22991942
TI  - BDNF as otoprotectant in toxin-induced hearing loss.
AB  - CONCLUSION: Brain-derived neurotrophic factor (BDNF) can prevent auditory
      brainstem response (ABR) threshold shift changes caused by Pseudomonas aeruginosa
      exotoxin A (PaExoA). OBJECTIVE: Peptides of the neurotrophin family are known to
      prevent neuronal death during embryonic development by interacting with specific
      membrane receptors. The purpose of this study was to investigate whether a single
      dose of BDNF is an effective protectant against toxic effects of PaExoA-induced
      ABR threshold shifts. MATERIALS AND METHODS: Eight groups of Sprague-Dawley rats
      were used. There were five control groups (n = 20) as follows. Group A (n = 4)
      received NaCl solution; group B (n = 3) received 4 ug BDNF; group C (n = 4)
      received 1 MUg/20 MUl PaExoA; group D (n = 4) received 2 MUg/20 MUl PaExoA; group
      E (n = 5) received 10 ug/20 ul PaExoA injected into the round window niche. Three
      treatment groups (n = 13) received a single dose of PaExoA and 4 ug of BDNF
      simultaneously. Group 1 (n = 3) received 1 MUg/20 MUl PaExoA + 4 ug of BDNF;
      group 2 (n = 5) received 2 MUg/20 MUl PaExoA + 4 ug BDNF; group 3 (n = 5)
      received 10 MUg/20 MUl PaExoA + 4 ug BDNF. ABR was used to measure efficacy by
      analyzing threshold shifts before and after injections. RESULTS: A single dose of
      BDNF prevented changes in ABR thresholds following exposure to increasing
      concentrations of PaExoA injected into the middle ear.

PMID- 22991943
TI  - New sulfonated polystyrene and styrene-ethylene/butylene-styrene block copolymers
      for applications in electrodialysis.
AB  - In this study we prepared blends of polystyrene (PS) and high-impact polystyrene
      (HIPS) with poly(styrene-ethylene-butylene) (SEBS) triblock copolymer. After
      sulfonation, blends were used to fabricate ion-exchange membranes by solvent
      casting and subsequent thermal treatment to obtain homogeneous packing densities.
      The morphology and structure of the blends were investigated by scanning electron
      microscopy, atomic force microscopy, and FTIR spectroscopy. Furthermore, the
      thermal transitions and stability of all the blends were characterized using
      calorimetric techniques and compared with those of the individual polymers.
      Analyses of the physical properties (i.e., ionic conductivity, ion-exchange
      capacity, water uptake, dimensional stability, mechanical properties, etc.)
      showed that the performance of the PS-containing membranes is, in general, higher
      than that of the HIPS containing one. Furthermore, the highest sulfonation degree
      was also found for the PS/SEBS membranes. The capabilities of the membranes were
      tested by investigating the extraction of Na(+) by electrodyalisis. Comparison of
      the percentage of extracted ions indicates that the incorporation of SEBS results
      in a significant improvement with respect to membranes made of individual
      polymers.

PMID- 22991944
TI  - Molecular filter on-chip design for drug targeting use.
AB  - This paper presents the use of a modified add/drop optical filter incorporating
      with microring resonators known as a PANDA microring resonator system which can
      fabricate on small chip. By using an optical tweezer, the required molecules can
      be trapped and moved to the required destinations at the add/drop ports. The
      novelty is that the stored molecules in the designed chip can transport via the
      optical waveguide and can also be used to form molecular filter, which is an
      important technique for drug delivery, drug targeting, and molecular electronics.
      Results have shown that the multivariable filter can be obtained by tunable
      trapping control.

PMID- 22991945
TI  - Toward anisotropic materials via forced assembly coextrusion.
AB  - Multilayer coextrusion offers a diverse platform to examine layer dependent
      confinement effects on self-assembling nanomaterials via conventional extrusion
      technology. A triblock copolymer (BCP) with a cylindrical microstructure was
      processed via "forced assembly" to elucidate the effect of microdomain
      orientation on the mechanical behavior of multilayer films. The mechanical
      response was investigated in both the extrusion (ED) and transverse directions
      (TD) of the multilayer systems, revealing an influence of both cylinder
      orientation and the interface on the mechanical response with decreasing layer
      thickness. The stress-strain curves for samples with the stress field along the
      cylinder axis revealed a sharp yielding phenomenon, while curves for specimens
      with the stress field applied perpendicular to the axis exhibited weak yielding
      behavior. The extensibility of the multilayer films stressed in the ED increases
      with decreasing layer thickness, but remains constant when deformed along the TD.
      Coextrusion technology allows for tunable mechanical toughness in industrial
      grade polymers via a continuous process. By altering the layer thickness of the
      two polymeric materials, we can tune the mechanics from strong, brittle behavior
      to a tough, ductile response by manipulation of the hierarchical structure. The
      enabling technology provides a unique platform to couple the inherent mechanical
      response of dissimilar polymers and allows for the design of composite materials
      with tailored mechanics.

PMID- 22991946
TI  - Nitroxyl radical/PhI(OAc)2: one-pot oxidative cleavage of vicinal diols to
      (di)carboxylic acids.
AB  - A mild and user-friendly one-pot oxidative cleavage of vicinal diols to their
      corresponding (di)carboxylic acids using AZADOs and PhI(OAc)(2) is described. 1,2
      Diols and 2,3-diols as well as 1,2,3-triol gave one- or two-carbon-unit-shorter
      carboxylic acids. Internal vicinal diols also smoothly underwent one-pot
      oxidative cleavage to afford the corresponding dicarboxylic acids. Cyclic vicinal
      diols are converted to their corresponding open-form dicarboxylic acids.

PMID- 22991947
TI  - Ultraviolet photoinitiated on-fiber copolymerization of ionic liquid sorbent
      coatings for headspace and direct immersion solid-phase microextraction.
AB  - A high-throughput method for the production of solid-phase microextraction (SPME)
      sorbent coatings via ultraviolet (UV) photoinitiated copolymerization of ionic
      liquid (IL) monomers on a fused silica support is described. The copolymerization
      of monocationic and dicationic IL cross-linkers was performed "on-fiber" using UV
      initiated free radical polymerization. Mixtures composed of various amounts of
      the IL cross-linker, UV initiator (DAROCUR 1173), and IL monomer were dip-coated
      onto an etched and derivatized fused silica support and placed in a high-capacity
      UV reactor. The method requires no organic dispersive solvent and is much more
      rapid compared to traditional methods in which polymeric ionic liquid (PIL)
      sorbent coatings are prepared by 2,2'-azobis(2-methylpropionitrile) (AIBN)
      initiated polymerization. Two ionic liquid-based cross-linkers, namely, 1,8-di (3
      vinylimidazolium) octane dibromide ([(VIM)(2)C(8)] 2[Br]) and 1,12-di (3
      vinylimidazolium) dodecane dibromide ([(VIM)(2)C(12)] 2[Br]), were copolymerized
      with an ionic liquid monomer, 1-vinyl-3-hexylimidazolium chloride ([VHIM][Cl]),
      to produce polar cross-linked PIL-based SPME sorbent coatings. The cross-linking
      and immobilization of these coatings make them particularly applicable in direct
      immersion SPME. The coatings were applied in the extraction of polar analytes,
      including alcohols, aldehydes, and esters, from aqueous solutions using headspace
      and direct immersion SPME gas chromatography mass spectrometry (GC/MS). Compared
      to linear PIL-based sorbent coatings containing the same anions, the cross-linked
      PIL-based coatings exhibited higher thermal stability and lower bleed, making
      them ideal for GC/MS. Recovery experiments were performed in deionized, well, and
      river water. The structural integrity of the sorbent coatings, as well as their
      analytical precision, was not diminished after 90 extractions from complex
      samples using headspace and direct immersion SPME.

PMID- 22991948
TI  - Eradication of nasopharyngeal carriage of penicillin-non-susceptible
      Streptococcus pneumoniae--is it possible?
AB  - BACKGROUND: The South Swedish Pneumococcal Intervention Project (SSPIP) was
      started in 1995 with the aim of limiting the spread of penicillin-non-susceptible
      pneumococci (PNSP) in Skane County, Sweden. As part of the SSPIP, eradication
      therapy with rifampicin in combination with 1 more antibiotic was considered on a
      social indication after prolonged carriage of 2-3 months. METHODS: In this
      retrospective study, 125 medical records were analyzed. Children aged 0-10 y
      referred for eradication therapy in Malmo and Lund, due to a prolonged
      nasopharyngeal carriage of PNSP with a penicillin G minimum inhibitory
      concentration of >= 0.5 mg/l, between the y 1997 and 2011 were included. Two
      consecutive negative cultures, with the second one no shorter than 7 days after
      treatment completion, were required for the carriage to be considered eradicated.
      RESULTS: Out of 125 children, 71 received treatment with rifampicin in
      combination with amoxicillin (n = 44), erythromycin (n = 22), or clindamycin (n =
      5) for 7 days. Eradication treatment was successful in 91.5% of the children. Six
      children (8.5%) had treatment failure with amoxicillin and rifampicin; 3 were
      found by late follow-up. There was a trend towards a better outcome with
      erythromycin and clindamycin combinations in comparison to amoxicillin.
      CONCLUSIONS: Eradication therapy was successful, but a proper follow-up is
      essential.

PMID- 22991949
TI  - Secondary health conditions in persons with a spinal cord injury for at least 10
      years: design of a comprehensive long-term cross-sectional study.
AB  - PURPOSE: To describe the prevalence of secondary health conditions (SHCs)
      (urinary tract and bowel problems, pressure ulcers, spasticity, musculoskeletal
      and neuropathic pain, sexual dysfunction, respiratory and cardiovascular
      disorders) in persons with long-term spinal cord injury (SCI), and to explore the
      impact of SHCs on fitness, active lifestyle, participation and well-being.
      METHODS: A time since injury (TSI)-stratified cross-sectional study among 300
      persons between 28- and 65-year-old with a SCI for at least 10 years. Strata of
      TSI are 10-19, 20-29, and 30 or more years. All eight Dutch rehabilitation
      centres with a SCI unit will participate. Participants will be invited for a 1
      day visit to the rehabilitation centre for an aftercare check-up by the local SCI
      rehabilitation physician (neurological impairment, SHCs and management), physical
      tests by a trained research assistant (lung function, wheelchair skills, physical
      capacity), and they will be asked to complete a self-report questionnaire in
      advance. RESULTS: Not applicable. CONCLUSION: This study will provide knowledge
      on the health status and functioning of persons aging with SCI living in the
      Netherlands. This knowledge will help us to develop predictive models for the
      occurrence of SHCs and to formulate guidelines to improve health care for persons
      with long-term SCI.

PMID- 22991950
TI  - Body mass does not affect the remission of psoriatic arthritis patients on anti
      TNF-alpha therapy.
AB  - OBJECTIVES: There is evidence that fat tissue may influence the response to
      therapy in patients with arthritis. The aim of this study was to assess whether
      the body mass index (BMI) affects rates of clinical remission in patients with
      psoriatic arthritis (PsA) treated with anti-tumour necrosis factor (TNF)-alpha
      biological drugs. METHOD: We retrospectively studied 135 patients with active
      peripheral PsA (45 obese, 47 overweight, and 43 normal-weight). Baseline BMI was
      correlated with the clinical response to adalimumab, etanercept, or infliximab.
      After 36 months (median, range 6-79) of treatment, disease remission rates were
      assessed using the Disease Activity Score in 28 joints (DAS28) or the Simplified
      Disease Activity Index (SDAI). Possible predictors of clinical outcomes were
      assessed by multivariate analysis. RESULTS: At baseline, BMI was significantly
      correlated only with the Health Assessment Questionnaire (HAQ) score (r = 0.21, p
      = 0.02) and not with disease activity. BMI did not predict disease remission or
      changes in HAQ score following anti-TNF-alpha therapy. Obese patients showed a
      significantly higher HAQ score and took significantly lower doses of prednisone
      than normal-weight or overweight patients, but their disease remission rates on
      the DAS28 (37%) or the SDAI (21%) were not significantly different from those of
      the other two groups (44% and 21%, respectively), regardless of the TNF-alpha
      inhibitor prescribed. CONCLUSIONS: In our retrospective analysis, disease
      activity and clinical response to anti-TNF-alpha therapy in PsA do not seem to be
      affected by BMI. Further prospective studies are needed to confirm these
      preliminary results.

PMID- 22991951
TI  - Novel cytidine-based orotidine-5'-monophosphate decarboxylase inhibitors with an
      unusual twist.
AB  - Orotidine-5'-monophosphate decarboxylase (ODCase) is an interesting enzyme with
      an unusual catalytic activity and a potential drug target in Plasmodium
      falciparum, which causes malaria. ODCase has been shown to exhibit unusual and
      interesting interactions with a variety of nucleotide ligands. Cytidine-5'
      monophosphate (CMP) is a poor ligand of ODCase, and CMP binds to the active site
      of ODCase with an unusual orientation and conformation. We designed N3- and N4
      modified CMP derivatives as novel ligands to ODCase. These novel CMP derivatives
      and their corresponding nucleosides were evaluated against Plasmodium falciparum
      ODCase and parasitic cultures, respectively. These derivatives exhibited improved
      inhibition of the enzyme catalytic activity, displayed interesting binding
      conformations and unusual molecular rearrangements of the ligands. These findings
      with the modified CMP nucleotides underscored the potential of transformation of
      poor ligands to ODCase into novel inhibitors of this drug target.

PMID- 22991953
TI  - Constructions of lesbian, gay, bisexual and queer identities among young people
      in contemporary Australia.
AB  - This paper focuses on young people's construction of lesbian, gay, bisexual and
      queer (LGBQ) identities in contemporary Australia. Through the perspectives of
      young people, it seeks to position their understanding of LGBQ identities
      alongside current theoretical and empirical debates about the individual and
      social significance attached to these identity frames. In this qualitative study,
      28 young people (aged 18 to 26 years) shared their stories of identifying as LGBQ
      through online, face-to-face or telephone interviews. The findings highlight how
      varying elements of LGBQ identities continue to have currency within this group
      and how young people adopt and refer to these terms interchangeably and in
      tandem. This is balanced alongside an awareness of both the limitations of
      lesbian, gay, bisexual and queer identity categories and of the homophobic
      discourses informing these subject positions. The paper concludes by arguing that
      health and social care professionals have a integral role to play in supporting
      LGBQ youth through a process of co-authorship - to work in partnership to
      construct more enabling self-stories that transcend restrictive identity frames.

PMID- 22991955
TI  - Electronic fetal monitoring: a bridge too far.

PMID- 22991954
TI  - A new bergenin derivative from the rhizome of Ardisia gigantifolia.
AB  - One new bergenin derivative, named 11-O-veratroylbergenin (1) along with five
      known bergenin derivatives, 11-O-(3'-O-methylgalloyl) bergenin (2), 11-O
      syringylbergenin (3), 11-O-Galloylbergenin (4), 4-O-Galloylbergenin (5) and
      bergenin (6) were isolated from Ardisia gigantifolia Stapf. Their structures were
      established on the basis of spectroscopic analysis, especially by means of 1D, 2D
      NMR and HR-ESIMS analyses. Compounds 2, 4 and 5 showed significant 2,2-diphenyl-1
      picrylhydrazyl (DPPH) free-radical scavenging activity with EC50 9.7, 9.0 and 7.8
      umol L(-1), respectively. They showed more antioxidant activity than the positive
      control vitamin C (EC50 = 28.3 umol L(-1)).

PMID- 22991956
TI  - Pharmaceutical detailing is not for everyone: side effects may include sub
      optimal prescribing decisions, compromised patient health, and increased
      prescription drug spending.

PMID- 22991952
TI  - Factors associated with completion of a behavioral intervention for caregivers of
      urban children with asthma.
AB  - BACKGROUND: Rates of preventive follow-up asthma care after an acute emergency
      department (ED) visit are low among inner-city children. We implemented a novel
      behavioral asthma intervention, Pediatric Asthma Alert (PAAL) intervention, to
      improve outpatient follow-up and preventive care for urban children with a recent
      ED visit for asthma. OBJECTIVE: The objective of this article is to describe the
      PAAL intervention and examine factors associated with intervention completers and
      noncompleters. METHODS: Children with persistent asthma and recurrent ED visits
      (N = 300) were enrolled in a randomized controlled trial of the PAAL intervention
      that included two home visits and a facilitated follow-up visit with the child's
      primary care provider (PCP). Children were categorized as intervention
      completers, that is, completed home and PCP visits compared with noncompleters,
      who completed at least one home visit but did not complete the PCP visit. Using
      chi-square test of independence, analysis of variance, and multiple logistic
      regression, the intervention completion status was examined by several
      sociodemographic, health, and caregiver psychological variables. RESULTS:
      Children were African-American (95%), Medicaid insured (91%), and young (aged 3-5
      years, 56%). Overall, 71% of children randomized to the intervention successfully
      completed all home and PCP visits (completers). Factors significantly associated
      with completing the intervention included younger age (age 3-5 years: completers,
      65.4%; noncompleters, 34.1%; p < .001) and having an asthma action plan in the
      home at baseline (completers: 40%; noncompleters: 21%; p = .02). In a logistic
      regression model, younger child age, having an asthma action plan, and lower
      caregiver daily asthma stress were significantly associated with successful
      completion of the intervention. CONCLUSIONS: The majority of caregivers of high
      risk children with asthma were successfully engaged in this home and PCP-based
      intervention. Caregivers of older children with asthma and those with high stress
      may need additional support for program completion. Further, the lack of an
      asthma action plan may be a marker of preexisting barriers to preventive care.

PMID- 22991957
TI  - The road to health is a battle hard fought: support for requiring coverage of
      bariatric surgery for an expanded group of qualified individuals.

PMID- 22991959
TI  - Pharmacokinetic properties of intravitreal I-124-aflibercept in a rabbit model
      using PET/CT.
AB  - PURPOSE: To determine the anatomic characteristics and pharmacokinetic properties
      of intravitreally-placed aflibercept in a rabbit model. MATERIALS AND METHODS:
      Four Dutch-belted rabbits underwent intravitreal injection with I-124
      aflibercept. Serial imaging with PET/CT imaging was performed on days 0, 2, 5, 7,
      14, 21, 28 and 35. Measured radioactivity emission in becquerels/mL was used to
      calculate the half-lives for aflibercept. RESULTS: I-124 aflibercept was confined
      within the vitreous cavity for the duration of the study. I-124 aflibercept could
      be detected in the vitreous cavity until day 28 and the average retention time
      with standard error after correction for radioactive decay was 4.58 +/- 0.07
      days. CONCLUSIONS: I-124 aflibercept was only visible in the vitreous cavity by
      PET/CT imaging following intravitreal injection. The retention properties were
      found to be comparable to those measured by other reported methods.

PMID- 22991960
TI  - Risk factors for acquisition of CTX-M-15 extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae during an outbreak in a neonatal intensive care
      unit in Norway.
AB  - BACKGROUND: A CTX-M-15 extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae was responsible for an outbreak in the neonatal intensive
      care unit (NICU) at Stavanger University Hospital, Norway over a 5-month period
      (November 2008-April 2009). The risk factors for acquiring ESBL-producing K.
      pneumoniae during the outbreak were examined in this study. METHODS: Faecal or
      rectal cultures were obtained from infants hospitalized in the NICU during the
      outbreak period and examined for ESBL-producing K. pneumoniae. Data were
      retrospectively retrieved from the medical records, including sex, gestational
      age, birth weight, indwelling central vascular catheter, continuous positive
      airway pressure (CPAP), mechanical ventilation, parenteral nutrition, antibiotic
      treatment, mode of delivery (vaginal vs caesarean), length of hospital stay, and
      mortality. RESULTS: A total of 216 infants were hospitalized in the NICU during
      the outbreak period, of whom 212 were screened; 51 (24%) scored positive for
      faecal colonization with ESBL-producing K. pneumoniae. One infant acquired a
      clinical infection. Forty-four colonized infants and 55 non-colonized infants
      were included in the risk analysis. Colonized infants had a lower birth weight,
      lower gestational age, and a longer hospital stay compared to non-colonized
      infants. By logistic regression, prematurity (gestational age <37 weeks) and
      treatment with antibiotics were independent risk factors for acquiring ESBL
      producing K. pneumoniae in the final model. CONCLUSION: Prematurity and treatment
      with antibiotics were independent risk factors for colonization during this NICU
      outbreak with ESBL-producing K. pneumoniae.

PMID- 22991961
TI  - Inkjet printing and release of monodisperse liquid crystal droplets from solid
      surfaces.
AB  - Recently, liquid crystal (LC) droplets in aqueous solutions have become a new
      platform for chemical and biological sensing applications. In this work, we
      present a two-step method to generate monodisperse LC droplets in aqueous
      solutions for sensing applications. In the first step, we exploit inkjet printing
      to dispense uniform LC droplets on a solid surface. Uniform LC droplets, ranging
      from 35 to 136 MUm in diameter, can be prepared by printing multiple times on the
      same spot. In the second step, we flush the LC droplets with a stream of aqueous
      solution in an open rectangular channel. Factors that determine the
      polydispersity of the LC droplets include flow rates and surface wettability.
      Under appropriate experimental conditions (i.e., when the surface is glass and
      the flow rate is sufficiently high), the LC droplets can be lifted off completely
      and carried away by the solution, forming free LC droplets (15-62 MUm in
      diameter). These free LC droplets can respond to a chemical reaction and change
      their optical textures uniformly.

PMID- 22991962
TI  - Natural carriers for application in tuberculosis treatment.
AB  - Tuberculosis remains the leading cause of preventable deaths worldwide and
      unsuccessful therapy is mainly due to non-compliance with very prolonged
      treatments, often associated with severe side-effects. Overcoming this problem
      demands the introduction of drug carriers releasing the antimicrobial agents in a
      targeted and sustained manner, allowing reduction in frequency and dosing
      numbers. Nano- and microparticles have taken the forefront of this approach,
      providing the means for the desired improvement of therapeutic schedules. Natural
      polymers are strong candidates as matrix-forming materials, usually exhibiting
      biocompatibility, biodegradability, low cost and some technological advantages as
      compared with synthetic counterparts. In this review, natural particulate
      carriers developed for tuberculosis therapy are presented, mainly focusing on the
      use of polysaccharides and lipids. Their effectiveness is discussed taking into
      account their composition. Finally, considerations on the general potential of
      natural materials for this application, as well as key factors still to be
      addressed, are discussed.

PMID- 22991963
TI  - Psychological factors that may confer risk for bipolar disorder.
AB  - Several psychological domains may be dysfunctional in people with bipolar
      disorder (BD). When dysfunction occurs prior to onset of mood symptoms, it may
      signify risk for onset of the full syndrome of illness. Among these domains,
      cognitive dysfunction has received considerable attention as a possible
      endophenotype for BD, with some suggestion that changes in cognitive function may
      antedate onset of mood symptoms in individuals at risk for BD. Domains of social
      cognition, including emotion comprehension, theory of mind, and empathy, along
      with autobiographical memory, represent understudied aspects of psychological
      function that may be dysfunctional in people with BD. Temperament and personality
      factors, such as ruminative tendencies and neuroticism, may also leave some
      people vulnerable to mood instability. This review summarises the evidence for
      dysfunction in each of these domains for people with BD and examines whether
      there is any evidence that this dysfunction antedates the onset of mood symptoms
      or confers risk for illness.

PMID- 22991964
TI  - Stereodynamics in eight-coordination; a 2D NMR spectroscopic and computational
      study of the exchange process in ThCl4(Me2NCH2CH2NMe2)2.
AB  - The (13)C{(1)H} NMR spectrum of eight-coordinate ThCl(4)(tmed)(2), where tmed =
      Me(2)NCH(2)CH(2)NMe(2), shows that two isomers are present at 219.8 K in a ratio
      of ~8:1 and inversion of the five-membered Th-tmed ring is slow at this
      temperature in both isomers. The 2D (13)C{(1)H} exchange spectroscopy (EXSY)
      spectrum shows that each of the two inequivalent methyl groups of the major
      isomer does not exchange directly with each other but that they both exchange
      with both of the two inequivalent methyl groups found in the minor isomer. This
      implies that interconversion of the two enantiomers of the major isomer proceeds
      by a stepwise process that involves the minor isomer. The interconversion of the
      isomers involves a ring-inversion process that may proceed with or without Th-N
      bond breaking, and the NMR spectra cannot distinguish between these two processes
      nor can density functional theory (DFT) calculations (B3PW91 and M06 with
      consideration of dispersion effects and solvent) because these two possibilities
      proceed by way of transition states of similar energies in this case.

PMID- 22991965
TI  - Ordering of the N-terminus of human MDM2 by small molecule inhibitors.
AB  - Restoration of p53 function through the disruption of the MDM2-p53 protein
      complex is a promising strategy for the treatment of various types of cancer.
      Here, we present kinetic, thermodynamic, and structural rationale for the
      remarkable potency of a new class of MDM2 inhibitors, the piperidinones. While
      these compounds bind to the same site as previously reported for small molecule
      inhibitors, such as the Nutlins, data presented here demonstrate that the
      piperidinones also engage the N-terminal region (residues 10-16) of human MDM2,
      in particular, Val14 and Thr16. This portion of MDM2 is unstructured in both the
      apo form of the protein and in MDM2 complexes with p53 or Nutlin, but adopts a
      novel beta-strand structure when complexed with the piperidinones. The ordering
      of the N-terminus upon binding of the piperidinones extends the current model of
      MDM2-p53 interaction and provides a new route to rational design of superior
      inhibitors.

PMID- 22991966
TI  - Identification of early fumonisin biosynthetic intermediates by inactivation of
      the FUM6 gene in Fusarium verticillioides.
AB  - Fumonisins are polyketide mycotoxins produced by the maize pathogen  Fusarium
      verticillioides  and are associated with multiple human and animal diseases. A
      fumonisin biosynthetic pathway has been proposed, but structures of early pathway
      intermediates have not been demonstrated. The F. verticillioides FUM6 gene is
      required for an early pathway step. Here, metabolites produced by strains of the
      fungus with an inactivated FUM6 gene were purified and shown by mass spectrometry
      and NMR spectroscopy to have fumonisin-like structures but without substitutions
      at C-14 and C-15. The major metabolite was 2-amino-12,16-dimethylicosane-3,10
      diol. Lesser amounts of 3-keto and triol analogues of the metabolite were also
      identified. In precursor feeding experiments, 2-amino-12,16-dimethylicosane-3,10
      diol was transformed to fumonisins by a F. verticillioides strain with an
      inactive fumonisin polyketide synthase gene. The results support the hypothesis
      that the FUM6-encoded enzyme catalyzes fumonisin C-14 and C-15 hydroxylation and
      provide direct spectroscopic and biochemical evidence for structures of early
      intermediates in fumonisin biosynthesis.

PMID- 22991967
TI  - Electrophilic assistance to the cleavage of an RNA model phopshodiester via
      specific and general base-catalyzed mechanisms.
AB  - Kinetics of transesterification of the RNA model substrate 2-hydroxypropyl 4
      nitrophenyl phosphate promoted by Mg(2+) and Ca(2+), the most common biological
      metals acting as cofactors for nuclease enzymes and ribozymes, as well as by
      Co(NH(3))(6)(3+), Co(en)(3)(3+), Li(+), and Na(+) cations, often employed as
      mechanistic probes, was studied in 80% v/v (50 mol %) aqueous DMSO, a medium that
      allows one to discriminate easily specific base (OH(-)-catalyzed) and general
      base (buffer-catalyzed) reaction paths. All cations assist the specific base
      reaction, but only Mg(2+) and Na(+) assist the general base reaction. For Mg(2+)
      assisted reactions, the solvent deuterium isotope effects are 1.23 and 0.25 for
      general base and specific base mechanisms, respectively. Rate constants for
      Mg(2+)-assisted general base reactions measured with different bases fit the
      Bronsted correlation with a slope of 0.38, significantly lower than the slope for
      the unassisted general base reaction (0.77). Transition state binding constants
      for catalysts in the specific base reaction (K(?)(OH)) both in aqueous DMSO and
      pure water correlate with their binding constants to 4-nitrophenyl phosphate
      dianion (K(NPP)) used as a minimalist transition state model. It was found that
      K(?)(OH) ~ K(NPP) for "protic" catalysts (Co(NH(3))(6)(3+), Co(en)(3)(3+),
      guanidinium), but K(?)(OH) ? K(NPP) for Mg(2+) and Ca(2+) acting as Lewis acids.
      It appears from results of this study that Mg(2+) is unique in its ability to
      assist efficiently the general base-catalyzed transesterification often occurring
      in active sites of nuclease enzymes and ribozymes.

PMID- 22991968
TI  - Acne vulgarism treatment using ultra-short laser pulse generated by micro- and
      nano-ring resonator system.
AB  - Acne vulgaris is adebilitating dermatologic disease, and is conventionally
      treated by laser therapy using a microring resonator system. An evolving
      understanding of laser-tissue interactions involving Propioni bacterium
      acneproducing porphyrins, and the development of lasers to target the sebaceous
      glands, has led to the development of an escalating number of laser light for
      acne treatment. The results show that the full width at half maximum of the
      proposed laser pulse of 0.15 nm can be generated using a microring resonator
      system. The power of the laser is 200 W and the wavelength laser is 1,032 nm,
      which is proposed as a treatment of acne vulgaris diseases.

PMID- 22991969
TI  - Fmoc-based synthesis of peptide thioacids for azide ligations via 2-cyanoethyl
      thioesters.
AB  - Rapid and efficient preparation of peptide thioacids from 2-cyanoethyl peptide
      thioesters has been accomplished. S-2-Cyanoethyl peptide thioesters were obtained
      cleanly without the need for purification from resin-bound tert-butyl peptide
      thioesters using 3-mercaptopropionitrile as a nucleophile. Elimination of the 2
      cyanoethyl group proceeded rapidly (t(1/2) < 8 min) under mild conditions and
      furnished peptide thioacids up to the size of a 16-mer. Peptide thioacids could
      be isolated or formed in situ and reacted smoothly with electron-deficient azides
      yielding an amide as the ligation product.

PMID- 22991970
TI  - Antimycobacterial drugs currently in Phase II clinical trials and preclinical
      phase for tuberculosis treatment.
AB  - INTRODUCTION: In 2010, about 8.8 million new cases of tuberculosis were recorded
      and 1.1 million people died of tuberculosis worldwide. Although numbers are in
      decrease since 2006, tuberculosis still represents a global issue and a major
      public health threat, due to appearance of multidrug-resistant and extensively
      drug-resistant tuberculosis cases. Although anti-tuberculosis drugs currently
      used are effective against tuberculosis, they present however more and more
      limits, especially in treating complex cases of tuberculosis, increasing
      therefore the need to develop new tools and approaches to treat tuberculosis
      today. AREAS COVERED: In this review, we describe anti-tuberculosis drugs in
      Phase II clinical trials and in preclinical phase that are likely to play a
      crucial role in the management of tuberculosis cases in a near future. SQ109,
      TMC207, nitroimidazoles, and oxazolidinones are currently in Phase II clinical
      trials while BDM31343, SQ641, CPZEN-45, RBx 8700, DC-159a, and BTZ043 are in
      preclinical phase. CONCLUSION: These drugs, alone or in different combinations
      represent a promising future for the treatment of tuberculosis. Continual
      conjugative efforts between governments and private organizations worldwide are
      essential for building new strategies for discovery and the development of new
      anti-tuberculosis drugs.

PMID- 22991971
TI  - Tryptophan switch for a photoactivated platinum anticancer complex.
AB  - The octahedral Pt(IV) complex trans,trans,trans-[Pt(N(3))(2)(OH)(2)(py)(2)] (1)
      is potently cytotoxic to cancer cells when irradiated with visible (blue) light.
      We show that the acute photocytotoxicity can be switched off by low doses (500
      MUM) of the amino acid l-tryptophan. EPR and NMR spectroscopic experiments using
      spin traps show that l-Trp quenches the formation of azidyl radicals, probably by
      acting as an electron donor. l-Trp is well-known as a mediator of electron
      transfer between distant electron acceptor/donor centers in proteins, and such
      properties may make the free amino acid clinically useful for controlling the
      activity of photochemotherapeutic azido Pt(IV) drugs. Since previous work has
      demonstrated the ability of photoactivated 1 to platinate DNA, this suggests that
      the high potency of such photoactive platinum complexes is related to their dual
      attack on cancer cells by radicals and Pt(II) photoproducts.

PMID- 22991972
TI  - Early hearing protection by brain-derived neurotrophic factor.
AB  - CONCLUSION: Brain-derived neurotrophic factor (BDNF) protects the inner ear from
      PaExoA (exotoxin A from Pseudomonas aeruginosa)-induced sensory neural hearing
      loss when administered 12 h after exotoxin, but not after 72 h. OBJECTIVE: BDNF
      is a peptide in the neurotrophin family with protective effects against noise
      induced hair cell loss and toxic inner ear damage following exposure to
      cisplatin. The exotoxin A (PaExoA) from P. aeruginosa, the most common
      microorganism in chronic suppurative otitis media, induces sensorineural hearing
      loss in rats. Previous study showed that, when given simultaneously with the
      exotoxin, BDNF protected the inner ear from damage. The aim of this study was to
      determine if BDNF has a protective effect when given 12-72 h after PaExoA.
      MATERIALS AND METHODS: Five groups of Sprague-Dawley rats were used. The three
      control groups (n = 16) were as follows. Group 1 (n = 8) received 15 ug/20 ul
      PaExoA; group 2 (n = 5) received 20 ug/20 ul PaExoA; and group 3 (n = 3) received
      25 ug/20 ul PaExoA injected into the round window niche. There were two treatment
      groups (n = 12): group A (n = 6) received 15 ug/20 ul PaExoA and 4 ug/20 ul BDNF
      12 h later; group B (n = 6) received 15 ug/20 ul PaExoA and 4 ug/20 ul BDNF 72 h
      later. Brainstem response audiometry (ABR) was performed on day 0 (control), and
      repeated on days 7, 14, 21, 28, and 35 to analyze the thresholds shifts. RESULTS:
      Exposure to 15 ug/20 ul PaExoA caused persistent and significant ABR impairment
      in controls when measured after 35 days. A single dose of BDNF given 12 h after
      PaExoA reduced hearing loss significantly, but when BDNF was given 72 h after
      PaExoA no protective effect was evident.

PMID- 22991973
TI  - Alginate and chitosan foam combined with electromembrane extraction for dried
      blood spot analysis.
AB  - Samples of 10 MUL of whole blood containing citalopram, loperamide, methadone,
      and sertraline as model substances were spotted on alginate and chitosan foams as
      sampling media. After drying and storage at room temperature, the punched out
      dried blood spot and the foam was dissolved in 300 MUL of 1 mM HCl. With alginate
      foam as sampling medium, the analytes dissolved completely after 3 min.
      Enrichment and cleanup was performed with electromembrane extraction for 10 min.
      The analytes were collected in 21 MUL of 10 mM formic acid as the acceptor phase,
      and the extracts were analyzed by liquid chromatography-mass spectrometry (LC
      MS). Sample preparation of blood spots on commercial cards was also performed
      (Whatman FTA DMPK and Agilent Bond Elut DMS) using elution procedures recommended
      by the manufacturers. The recoveries obtained with the commercial cards were
      lower for most of the model analytes compared to the recoveries obtained with
      alginate and chitosan foams as sampling media. The procedure used for Agilent
      Bond Elut DMS showed higher recoveries than the procedure used for Whatman FTA
      DMPK-A, but the time needed for sample preparation was significantly longer
      (nearly 2 h). The stability of the model substances on the alginate foam was
      acceptable within 50 days of storage. The limit of quantification (LOQ) defined
      as S/N = 10, was 1.2, 5.5, 2.0, and 5.3 ng/mL for citalopram, loperamide,
      methadone, and sertraline, respectively. Linear calibration graphs were obtained
      in the range 17.5-560 ng/mL with r(2) values 0.983-0.995, and the relative
      standard deviations were below 20%.

PMID- 22991974
TI  - Association of HLA-DRB1*01 with Dupuytren's disease.
AB  - OBJECTIVES: To explore the human leucocyte antigen (HLA)-DRB1 allele frequency in
      Dupuytren's disease (DD). METHOD: HLA-DRB1 genotypes were analysed by sequence
      specific primers (SSPs) in samples collected from 172 men participating in a
      nested case-control study on the clinical manifestations and progression of DD.
      Of those, 121 had signs of DD while 51 did not. Of the 121 men with DD, 49 had
      contracted fingers or had been operated on, while 72 had nodules or fibrous cords
      in the palms. Odds ratios (ORs) and 95% confidence interval (CIs) were used to
      evaluate the results. RESULTS: The HLA-DRB1*01 allele was observed in 26 of the
      121 affected men (23.7%) but in only four of the controls (7.8%) (OR 3.22, 95% CI
      1.06-9.75). The HLA-DRB1*01 allele frequency in those affected was 11%, while in
      the control group it was 4% (OR 3.07, 95% CI 1.05-9.03). CONCLUSIONS: This
      observation indicates a possible association of HLA-DRB1*01 with DD, but further
      studies are needed for confirmation.

PMID- 22991975
TI  - A nationwide study of mechanisms conferring reduced susceptibility to extended
      spectrum cephalosporins in clinical Escherichia coli and Klebsiella spp.
      isolates.
AB  - BACKGROUND: Enterobacteriaceae exerting a high level of extended-spectrum
      cephalosporin (ESC) resistance have increased significantly in Norway in the last
      decade. Various mechanisms acting alone or in concert mediate variable levels of
      ESC resistance and pose great challenges in the implementation of screening
      strategies and treatment. This study was undertaken to document the prevalence of
      underlying mechanisms conferring resistance to ESCs in a nationwide collection of
      clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Klebsiella
      oxytoca, before the increase in extended-spectrum beta-lactamase (ESBL)-producing
      strains. METHODS: Consecutive E. coli (n = 2213), K. pneumoniae (n = 303), and K.
      oxytoca (n = 66) isolates from 23 Norwegian diagnostic laboratories were
      collected and examined for reduced susceptibility to ESCs. Isolates displaying
      minimum inhibitory concentrations (MICs) of > 2 mg/l by Etest to cefpodoxime
      and/or MICs > 1 mg/l to any other ESCs were included (n = 54; 35 E. coli, 11 K.
      pneumoniae, and 8 K. oxytoca). Isoelectric focusing for the detection of beta
      lactamases, and polymerase chain reactions (PCRs) with subsequent sequencing for
      detection of ESBLs CTX-M, TEM, and SHV, plasmid-mediated AmpC, OXA subtypes, and
      alterations of porin genes ompC and ompF, and quantitative reverse transcriptase
      (RT)-PCR for investigation of enhanced expression of chromosomal ampC were
      performed. RESULTS: Eight E. coli isolates (0.4%) were ESBL producers and 20
      (1.0%) were hyperproducers of the chromosomal ampC. Three K. pneumoniae isolates
      (1.1%) were ESBL producers, and all K. oxytoca isolates (n = 8; 13.6%) were OXY
      hyperproducers. No definite mechanisms for reduced susceptibility to ESCs could
      be inferred for 7 E. coli (0.4%) and 8 K. pneumoniae (3.0%) isolates.
      CONCLUSIONS: This study identified chromosomal AmpC-hyperproducing E. coli and
      OXY-hyperproducing K. oxytoca in addition to ESBLs in Enterobacteriaceae as major
      mechanisms of resistance to ESC, and documented their rates of prevalence for the
      first time in Norway.

PMID- 22991976
TI  - 3D-QSAR studies of quinoline ring derivatives as HIV-1 integrase inhibitors.
AB  - In the process of HIV-1 virus replication, integrase plays a quite important
      role. Integrase inhibitors of quinoline ring derivatives were analysed by the
      Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity
      Induces Analysis (CoMSIA) and Topomer CoMFA methods. Firstly, 77 compounds were
      selected to form the training and test sets. Secondly, predictive models were
      constructed with the CoMFA, CoMSIA and Topomer CoMFA methods. The CoMFA model
      yielded the best model with q (2) of 0.76 and [Formula: see text] of 0.99, the
      CoMSIA model has q (2 )= 0.70 and [Formula: see text] of 0.99, while the Topomer
      CoMFA model has q (2) of 0.66 and [Formula: see text] of 0.97. These results
      provide a helpful contribution to the design of novel highly active HIV-1
      integrase inhibitors.

PMID- 22991977
TI  - Vitamin B12 derivatives as activators of soluble guanylyl cyclase.
AB  - Various newly prepared and previously known vitamin B12 derivatives have been
      studied as potential soluble guanylyl cyclase (sGC) activators. All compounds
      tested were found to activate the sGC enzyme, although to differing extents. The
      best results were obtained with the derivatives synthesized from c-lactone and
      possessing aliphatic amides in the c- and d-positions.

PMID- 22991978
TI  - Design and validation of a bioreactor for simulating the cardiac niche: a system
      incorporating cyclic stretch, electrical stimulation, and constant perfusion.
AB  - To simulate the cardiac niche, a bioreactor system was designed and constructed
      to incorporate cyclic stretch, rhythmic electrical stimulation, and constant
      perfusion. The homogeneity of surface strain distribution across the cell culture
      substrate was confirmed with ARAMIS deformation analysis. The proliferation
      marker, Ki-67, detected in human umbilical vein endothelial cells and 3-[4,5
      dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay
      performed on human atrial fibroblasts confirmed biocompatibility of this novel
      device. Cyclic stretch treatment for 24 h resulted in the perpendicular alignment
      of human atrial fibroblasts. An electrical stimulation system containing carbon
      electrodes was characterized by electrochemical impedance spectroscopy and charge
      injection/recovery studies, which indicated that increased corrosive reactions
      were associated with a higher input voltage and prolonged pulse duration. Field
      stimulation delivered through this system could induce rhythmic contractions in
      adult rat ventricular myocytes, with contractile characteristics similar to those
      paced in a standard field stimulation chamber. In conclusion, this bioreactor
      provides a novel tool to study the interaction between physical stimulation and
      cardiac cell physiology.

PMID- 22991979
TI  - Changes in calculated coronary heart disease risk using proactive multifactorial
      intervention versus continued usual care in Latin-American and non-Latin-American
      patients enrolled in the CRUCIAL trial.
AB  - OBJECTIVE: To compare the change in calculated coronary heart disease (CHD) risk
      using a proactive multifactorial intervention (PMI) versus usual care (UC), among
      Latin-American (LA) and non-LA patients enrolled in the CRUCIAL trial. RESEARCH
      DESIGN AND METHODS: This is a sub-analysis of the Cluster Randomized Usual Care
      versus Caduet Investigation Assessing Long-term-risk (CRUCIAL) trial. CRUCIAL was
      a prospective, multinational, open-label, cluster-randomized trial. Eligible
      patients had hypertension and >=3 additional cardiovascular risk factors, but no
      history of CHD and baseline total cholesterol <=6.5 mmol/l (250 mg/dl). The PMI
      strategy was implemented by the inclusion of single-pill amlodipine/atorvastatin
      (SPAA) in the patients' treatment regimen. Overall, 20% of patients resided in
      the LA region. MAIN OUTCOME MEASURE: Treatment-related change in calculated
      Framingham 10-year CHD risk between baseline and Week 52 in the LA and non-LA
      regions. RESULTS: A greater relative reduction in calculated CHD risk after 52
      weeks' follow-up was observed for patients in the PMI arm compared with UC arm in
      both LA (-32.8% vs. -7.5%, p = 0.003) and non-LA regions (-33.1% vs. -3.3%, p <
      0.001), region interaction p = 0.316. The proportion of patients discontinuing
      treatment in the PMI arm due to adverse events (AEs) was low in both regions
      (both 5.9%). CONCLUSIONS: The PMI approach based on the inclusion of SPAA in the
      patients' treatment regimen may improve the management of CHD risk among patients
      residing in LA and non-LA regions. Clinicians may be reassured by the low rate of
      AEs leading to discontinuation of SPAA in both regions.

PMID- 22991980
TI  - Charge and pressure-tuned surface patterning of surfactant-encapsulated
      polyoxometalate complexes at the air-water interface.
AB  - In this paper, four organic-inorganic hybrid complexes were prepared using a
      cationic surfactant dimethyldioctadecylammonium (DODA) to replace the counter
      cations of four Keggin-type polyoxometalate (POM) clusters with gradually
      increased negative charges, PW(12)O(40)(3-), SiW(12)O(40)(4-), BW(12)O(40)(5-),
      and CoW(12)O(40)(6-). The formed surfactant-encapsulated POM (SEP) complexes
      showed typical amphiphilic properties and can be spread onto the air-water
      interface to form Langmuir monolayers. The interfacial behavior of the SEP
      monolayer films was systemically studied by multiple in situ and ex situ
      characterization methods including Brewster angle microscopy (BAM), atomic force
      microscopy (AFM), reflection-absorption infrared (RAIR), and X-ray photoelectron
      spectroscopy (XPS). We found that the increasing alkyl chain density of SEPs
      leads to an enhanced stability and a higher collapse pressure of SEP Langmuir
      monolayers. Moreover, a second layer evolved as patterns from the initial
      monolayers of all the SEPs, when the surface pressures approached the collapse
      values. The rational combination of alkyl chain density and surface pressure can
      precisely control the size and the morphology of SEP patterns transforming from
      disk-like to leaf-like structures on a micrometer scale. The pattern formation
      was demonstrated to be driven by the self-optimized surface energy of SEP
      monolayers. This finding can direct a new strategy for the fabrication of POM
      hybrid films with controllable patterns, which should be instructive for
      designing POM-based thin film devices.

PMID- 22991981
TI  - An unexpected intracranial blade.
AB  - While self-mutilations with stab wounds are relatively common in psychiatric
      patients suffering from schizophrenia and personality disorders, they are rarely
      performed as suicidal attempts. Even in psychotic patients, suicidal stab wounds
      of the skull are rare in the literature. We report the case of a 34-year-old
      schizophrenic man whom emergency medical services (EMS) providers cared for at
      his home because of a complete self-amputation of his right hand, without any
      other apparent wound than a facial laceration. The patient was transferred to the
      acute surgical ward for evaluation of the possibility reimplantation of the
      amputated hand. When his neurologic status rapidly declined after hospital
      admission, a whole-body computed tomography (CT) scan was performed for other
      injuries. Unexpectedly, cerebral CT scan showed the presence of an intracranial
      11-cm-long blade, whose distal tip was located in the left temporal cerebral
      lobe. Given the nature of the cerebral injuries on CT scan and the major
      impairment of the neurologic status of the patient, the neurosurgeon considered
      surgical extraction of the blade to be futile, and the patient's condition
      rapidly deteriorated to brain death.

PMID- 22991982
TI  - Prevalence and determinants of hyperglycaemia in pneumonia patients.
AB  - BACKGROUND: Hyperglycaemia during pneumonia prolongs the hospitalization and
      increases the risks of complications and death. However, its prevalence and
      determinants have not been systematically assessed. METHODS: This was a
      prospective, cross-sectional study. The material consisted of 153 hospitalized
      patients with pneumonia. Patients needing intensive care unit treatment were
      excluded. The height, weight, waist circumference, oxygen saturation, blood
      pressure, temperature, heart rate, and Karnofsky score were measured at
      admission. Blood tests included glycosylated haemoglobin A1c (gHbA1c), C-reactive
      protein (CRP), leukocytes, urea, and arterial blood gas analysis. Plasma glucose
      was measured 7 times during the first day on the ward. Hyperglycaemia was defined
      as a fasting glucose > 7.0 mmol/l or postprandial glucose > 11.1 mmol/l. RESULTS:
      Ninety-two patients (60%) showed hyperglycaemia. Twenty-two patients had a
      diagnosis of diabetes before hospitalization. Of the 131 patients without such a
      diagnosis, 72 (55%) showed hyperglycaemia. Of these, 67 showed fasting
      hyperglycaemia and 36 postprandial hyperglycaemia. In the binary logistic
      regression analysis, the following factors showed independent associations with
      the presence of hyperglycaemia: advanced age, high gHbA1c, high CRP, and high
      blood leukocyte level. CONCLUSIONS: More than half of non-diabetic patients with
      mild to moderate pneumonia demonstrated hyperglycaemia. The main determinants of
      hyperglycaemia were an abnormal pre-pneumonia glucose metabolism and the
      intensity of the pneumonic inflammation. Systematic screening of hyperglycaemia
      in all hospitalized pneumonia patients appears reasonable to identify high-risk
      patients.

PMID- 22991983
TI  - Validity evidence of the Lateral Step Up (LSU) test for adolescents with spastic
      cerebral palsy.
AB  - PURPOSE: The present study examined the concurrent and construct validity of the
      Lateral Step Up (LSU) test, for adolescents with CP. METHOD: A total of 35
      adolescents, classified as GMFCS Levels I, II and III, were examined using LSU,
      GMFM - 88 (D & E), other functional mobility measures (TUG, STS, TUDS), body
      structures and functions (strength, ROM and spasticity). RESULTS: LSU inter
      correlations with: (i) GMFM - 88 (D & E) (r = 0.656), (ii) functional mobility
      measures (r = -0.567 to 0.721) and (iii) body structures and functions (r = 0.155
      to 0.563) were at the appropriate range. The LSU differentiated adolescents with
      CP (F = 16.185, p = 0.000, eta(2) = 0.503), according to their GMFCS (I > II, II
      > III, I > III). Finally, 50.27% of the LSU variability was explained by GMFCS
      differences, with 65.7% of adolescents classified correctly across the three
      levels. CONCLUSIONS: The LSU may be perceived as a valid instrument for assessing
      the functional mobility of adolescents with CP. IMPLICATIONS FOR REHABILITATION:
      * LSU is valid for assessing functional mobility and strength in CP adolescents.
      * LSU may be used in accordance with other functional mobility measures in the
      school environment. * The LSU may be used from physical therapists to predict the
      functional mobility of CP adolescents at GMFCS Levels I-III.

PMID- 22991984
TI  - [The use of botulinum toxin type A in masseter muscle hypertrophy: long-term
      effects and lasting improvement].
AB  - OBJECTIVES: In this study, we aimed to evaluate the long-term efficacy of
      botulinum toxin A injection in reducing the masseter muscle thickness. PATIENTS
      AND METHODS: Between 2007 and June 2008, we retrospectively analyzed the data
      from 28 patients (21 females, 7 males; mean age: 25.5+/-4.5 years; range 20 to 46
      years) with benign masseter hypertrophy treated with botulinum toxin A
      injections. All patients were diagnosed by the morphometric analysis of the
      masseter muscle. The injections were repeated intermittently every six months and
      totally for six times. The patients were recalled and the last measurement was
      performed at a mean follow-up of 13.2 months. RESULTS: The values obtained
      following consecutive injections were compared and a statistically significant
      reduction in thickness of masseter muscle thickness after every single injection
      was found (p<0.001). The final measurement following treatment discontinuation
      revealed that this reduction was long-lasting. CONCLUSION: Botulinum toxin A
      injection is a safe and long-term effective therapy for the masseter muscle
      hypertrophy.

PMID- 22991985
TI  - [The role of COX-2, ALOX12 and iNOS genes in nasal polyposis].
AB  - OBJECTIVES: The aim of this study was to investigate whether cyclooxygenase-2
      (COX-2), arachidonate 12-lipoxygenase (ALOX12) and inducible nitric oxide
      synthase (iNOS) which are well-known mediators in inflammatory process play a
      role in nasal polyposis (NP) and to show their roles in initiation and
      progression of inflammation. PATIENTS AND METHODS: We investigated the expression
      levels of COX-2, ALOX12 and iNOS genes by real-time polymerase chain reaction
      (PCR) method in NP tissues obtained from 10 patients (4 females, 6 males; mean
      age ?? years; range 21 to 54 years). RESULTS: The mRNA levels of COX-2 expression
      observed in NP was found to be relatively increased, compared to the control
      tissue (p>0.05). The ALOX12 levels were relatively decreased (p>0.05), while the
      expression level of iNOS mRNA was significantly higher in NP tissue (p<0.05).
      CONCLUSION: These data suggest that nitric oxide (NO), a gene product of iNOS,
      may play a physiological role in the upper airways and also NO is associated with
      inflammatory processes in the airways.

PMID- 22991986
TI  - [Local flap reconstruction of resected non-melanoma malignant skin tumors: a case
      series of 57 patients].
AB  - OBJECTIVES: In our study, we present a case series of 57 patients with non
      melanoma malignant skin cancer involving the face who were treated with local
      flap reconstruction with literature review. PATIENTS AND METHODS: Between
      February 2010 and September 2011, 57 patients (37 males, 20 females; mean age
      63.1 years; range 38 to 87 years) who were admitted to Unye State Hospital
      Otolaryngology and Head and Neck and Dermatology Clinic with a preliminary
      diagnosis of non-melanoma skin cancer were retrospectively analyzed in terms of
      tumor histopathologically, location and treatment plan. RESULTS: The tumor
      distribution of the patients included basal cell carcinoma (n=39, 68.4%) and
      squamous cell carcinoma (n=18, 31.4%). The mean follow-up was 14.2 (range 8-23
      months). The most common involvement site of the skin tumor was the nose (n=23,
      40.3%), followed by forehead (n=8, 14%), lips (n=7, 12.2%), ears (n=6, 10.5%),
      cheeks (n=6, 10.5%), eyes (n=3, 5.2%), chin (n=2, 3.5%) and neck (n=2, 3.5%).
      CONCLUSION: Local flap reconstruction applied following surgical excision of skin
      cancer is an effective treatment method which can easily be used by ear nose
      throat surgeons.

PMID- 22991987
TI  - Can carotid-sparing radiotherapy approaches replace with conventional techniques
      for the patients with T1 glottic larynx cancer?
AB  - OBJECTIVES: This study aims to compare the carotid artery doses applied with
      various radiotherapy techniques for the treatment of T1N0 glottic larynx cancer.
      PATIENTS AND METHODS: Five patients were simulated with using computed tomography
      (CT). Clinical (CTV) and planning target volumes (PTV) were created for T1N0
      glottic larynx cancer. Planning risk volumes (PRV) were constructed for carotid
      arteries and spinal cord. Three irradiation planning, opposed lateral box field
      (OLBF), three dimension conformal radiation therapy (3DCRT), intensity modulated
      radiation therapy (IMRT) were done for each patient. Over 95% of planned target
      volumes were loaded with predetermined dose (a total of 62.25 Gy of 2.25 Gy daily
      dose). RESULTS: The comparison of the treatment planning of five T1 glottic
      larynx cancer, three involving the right vocal cord and two involving the left
      vocal cord, the technique of IMRT planning was provided the best carotid-sparing
      doses. Mean carotid V35, V50, and V63 values including OLBF, 3DCRT, and IMRT were
      70%, 47%, 35%; 55%, 15%, 5% and 28%, 6%, 0%, respectively. The statistical
      comparison of V35, V50 and V63 revealed significant values for OLBF and IMRT.
      Dose of spinal cord did not exceed 45 Gy for any of radiation treatment planning.
      Between the three techniques, there was no significant difference in terms of
      conformity index and dose distribution was homogenous with all techniques.
      CONCLUSION: It is obvious that IMRT planning technique can decrease the carotid
      artery radiation doses in early stage glottic larynx cancer.

PMID- 22991988
TI  - Nasopharyngeal/nasal type NK/T lymphoma: analysis of 23 cases and current review
      of the literature.
AB  - OBJECTIVES: This study aims to identify the presenting symptoms, treatment and
      outcome of patients with nasal natural killer T (NK/T)-cell lymphoma and to find
      possible differences in survival based on Ann-Arbor stage and international
      prognostic index (IPI). PATIENTS AND METHODS: Computed tomography and biopsy
      results of 23 patients (15 males, 8 females; mean age 41 years; range 22 to 72
      years) with extranodal NK/T-cell lymphoma who were treated at the department of
      clinical hematology between 1995 and 2011 were retrospectively analyzed. RESULTS:
      The median time from onset of clinical symptoms to histological diagnosis was
      five months. Most patients presented with nasal obstruction (69%) and rhinism
      (52%). The site of extranodal NK/T-cell lymphoma primarily involved nasal cavity
      in 39%. Orbital extension was observed in 26%. Lymphomas were classified as stage
      IE in 30.4%, stage IIE in 47.8% and stage IVE in 21.7%. Nineteen patients
      received treatment: 10 received chemotherapy plus radiotherapy, nine received
      chemotherapy only. We used several regimens of chemotherapy including some
      protocols containing etoposid, L-asparaginase and others without this drugs.
      Univariate analysis showed that lower IPI score, low Ann-Arbor stage and
      responsiveness to treatment with both chemotherapy and radiotherapy were
      significant factors influencing both OS and PFS. CONCLUSION: Nasal type NK/T-cell
      lymphoma showed a poor response to the conventional anthracycline-based
      chemotherapy, thereby an investigation for a novel therapy is urgently needed to
      improve survival.

PMID- 22991990
TI  - Sclerosing polycystic adenosis of the parotid gland presenting with a Warthin
      tumor.
AB  - Sclerosing polycystic adenosis (SPA) frequently presents as an isolated process,
      however it may involve adjacent benign salivary gland neoplasia. In this article,
      we present a 77-year-old female case with a 10-year history of a slow-growing
      mass of the left parotid gland of SPA presenting with a Warthin tumor. The
      patient underwent left superficial parotidectomy. The histopathological
      examination revealed SPA and multifocal Warthin tumor.

PMID- 22991989
TI  - A case of an apocrine hidrocystoma treated by sublabial approach.
AB  - Apocrine hidrocystomas are uncommon cystic proliferations of the apocrine
      secretory glands. Maxilla is an unexpected involvement site for these tumors. Our
      study represents the first case of an apocrine hidrocystoma of the maxilla
      excised by an intraoral (sublabial) approach, being the first to define the
      radiologic findings of apocrine hidrocystoma on this region. This case is an
      extremely rare type in terms of the unusual symptomatology, location and size of
      the tumor. In this article, clinical presentation, surgical findings,
      histopathological features and treatment of this rare lesion were discussed.

PMID- 22991991
TI  - Wegener granulomatosis presenting as refractory otitis media: a case report.
AB  - Wegener's granulomatosis (WG) is a granulomatous widespread necrotizing
      vasculitis, sometimes progressing rapidly, characterized by a tendency to involve
      the upper and lower respiratory tracts, and in most cases, the kidneys. Otologic
      manifestations may be seen during the course of the disease, however, they are
      not frequently seen as the first and only presenting feature. The presence of
      anticytoplasmic antibodies versus neutrophil polymorphonucleate granules (c-ANCA)
      is highly specific for the diagnosis of WG, being positive in 97% of the cases.
      The early diagnosis and the timely medical treatment result in high rates of
      remission of this potentially lethal disease. In this article, we report a case
      of WG presenting with acute serous otitis media, progressing to suppurative
      otitis media and granulomas as the first and only symptom, which was refractory
      to medical therapy during follow-up and which was diagnosed with further
      examination.

PMID- 22991992
TI  - Fibromyxoma of the frontal sinus.
AB  - Fibromyxomas are uncommonly encountered pathologies in the head and neck region.
      They are slow growing, which result in expansion of the surrounding bony
      cortices. In this article, we report an extremely rare case of frontal sinus
      fibromyxoma which occluded the frontal sinus and expanded anterior ethmoid cells
      and nasal dorsum. Initially, it was suspected to be a mucocele. Surgical
      resection with a wide excision was performed and it was diagnosed as fibromyxoma,
      histopathologically.

PMID- 22991993
TI  - Incidentally detected asymptomatic metal foreign bodies (two nails) in
      shoemaker's maxillary sinus.
AB  - The diagnosis metal foreign bodies of maxillary sinus cannot be usually made in
      an acute setting and patients may present with chronic symptoms due to drainage
      and chronic irritation of the mucosa years later. Metal foreign bodies can be
      generally displaced to the maxillary sinus at the time of dental intervention. In
      this article, we report a very interesting case of 23-year-old male shoemaker
      with two metal foreign bodies (nails) which were non-related with any surgical
      intervention or trauma and found incidentally in the right maxillary sinus.

PMID- 22991994
TI  - Cerium(IV) tellurite halides [Ce2Te7O17]X2 (X = Cl- or Br-): the first cerium
      containing cationic frameworks.
AB  - Two isotypic cerium tellurite halides with the formulas [Ce(2)Te(7)O(17)]Cl(2)
      and [Ce(2)Te(7)O(17)]Br(2) have been synthesized hydrothermally via the reactions
      of CeCl(3) and CeBr(3) with TeO(2). The structures of these compounds feature a
      cationic inorganic framework. The Ce(IV) dimers are bound by a novel 3D
      Te(7)O(17)(6-) building unit, forming an unusual hexagonal-bipyramidal
      environment around Ce(IV).

PMID- 22991995
TI  - Studies on the chemical transformation of 20(S)-protopanaxatriol (PPT)-type
      ginsenosides R(e), R(g2), and R(f) using rapid resolution liquid chromatography
      coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS).
AB  - A rapid resolution liquid chromatography coupled with quadruple-time-of-flight
      mass spectrometry (RRLC-Q-TOF-MS) method was developed for analysis of chemical
      transformation of 20(S)-protopanaxatriol (PPT)-type ginsenosides Re, Rg2, and Rf
      in acidic conditions. The transformation products were identified by comparing
      the retention time of the standard compounds, the accurate mass measurement, and
      the fragment ions obtained from RRLC-Q-TOF-tandem mass spectrometry (MS/MS)
      analyses. The specific product ions of aglycone PPT (m/z 475), C-24- and C-25
      hydrated PPT (m/z 493), and Delta20(21) or Delta20(22) dehydration PPT (m/z 457)
      by MS/MS were discussed for structural characterization. Experiments demonstrated
      that chemical transformation mechanisms of 20(S)-PPT-type ginsenosides in acidic
      conditions include hydrolysis of saccharide substitution, Delta20(21) or
      Delta20(22) dehydration, and hydration addition reactions at C-24 and C-25. The
      chemical transformation pathway for 20(S)-PPT-type ginsenosides was summarized.
      The developed RRLC-Q-TOF-MS method was also applied for comparative analysis of
      20(S)-PPT ginsenoside and related chemical transformation products in ginseng
      products. 

PMID- 22991996
TI  - Identification of a p.R143Q dominant mutation in the gap junction beta-2 gene in
      three Chinese patients with different hearing phenotypes.
AB  - CONCLUSIONS: p.R143Q mutation in GJB2 can cause mild to profound bilateral
      sensorineural hearing impairment. Although not common in Chinese patients with
      hearing loss, it is important to identify the specific phenotype and genotype
      correlations of the dominant mutation in GJB2. OBJECTIVE: Mutations in the GJB2
      gene are the most common cause of nonsyndromic autosomal recessive sensorineural
      hearing loss. A few mutations in GJB2 have also been reported to cause dominant
      nonsyndromic or syndromic hearing loss. However, dominant mutation in GJB2 is not
      common in Chinese populations. METHODS: Three patients with hearing impairment
      from Chinese families are reported here. Temporal CT scan, complete physical
      (including skin and hair) and otoscopic examinations, and an audiological study,
      including tympanometry, auditory brainstem response (ABR), auditory steady-state
      response (ASSR), and 40 Hz auditory event-related potential (40 Hz-AERP), were
      carried out. The two exons of GJB2, the coding exons of SLC26A4, and
      mitochondrial 12S rRNA were sequenced. RESULTS: Sequencing of GJB2 in two
      patients showed a heterozygous c.428G>A (p.R143Q) mutation, and the third patient
      was identified with c.299delAT and c.428G>A compound heterozygous mutation.
      Sequence analysis of the coding exons of SLC26A4 and mitochondrial 12S rRNA was
      performed but no sequence aberration or deletion was found.

PMID- 22991997
TI  - Bis(1,3-di-tert-butylimidazolin-2-iminato) titanium complexes as effective
      catalysts for the monodisperse polymerization of propylene.
AB  - The use of bis(1,3-di-tert-butylimidazolin-2-iminato) titanium dichloride (1) and
      dimethyl (2) complexes in the polymerization of propylene is presented. The
      complexes were activated using different amounts of methylalumoxane (MAO), giving
      in each case a very active catalytic mixture and producing polymers with a narrow
      molecular weight distribution (polydispersity = 1.10). The use of the cocatalyst
      triphenylcarbenium (trityl) tetra(pentafluorophenyl)borate totally inhibits the
      reaction, producing the corresponding bis(1,3-di-tert-butylimidazolin-2-iminato)
      titanium(III) methyl complex, the trityl radical ((*)CPh(3)), the anionic
      MeB(C(6)F(5))(4)(-), B(C(6)F(5))(3), and the bis(1,3-di-tert-butylimidazolin-2
      iminato) titanium(IV) dimethyl.B(C(6)F(5))(3) complex. The use of a combination
      of physical methods such as NMR, ESR-C(60), and MALDI-TOF analyses enabled us to
      propose a plausible mechanism for the polymerization of propylene, presenting
      that the polymerization is mainly carried out in a living fashion. In addition,
      we present a slow equilibrium toward a small amount of a dormant species
      responsible for 2,1-misinsertions and chain transfer processes.

PMID- 22991998
TI  - Optimized agroinfiltration and virus-induced gene silencing to study Ve1-mediated
      Verticillium resistance in tobacco.
AB  - Recognition of pathogen effectors by plant immune receptors often leads to the
      activation of a hypersensitive response (HR), which is a rapid and localized cell
      death of plant tissue surrounding the site at which recognition occurs. Due to
      its particular amenability to transient assays for functional genetics, tobacco
      is a model for immune signaling in the Solanaceae plant family. Here, we show
      that coexpression of the tomato (Solanum lycopersicum) immune receptor Ve1 and
      the corresponding Verticillium effector protein Ave1 leads to HR only in
      particular tobacco species. Whereas HR is obtained in Nicotiana tabacum, no such
      response is obtained in N. benthamiana. Furthermore, our analysis revealed an
      endogenous Ve1 ortholog in Nicotiana glutinosa, as expression of Ave1 in absence
      of Ve1 induced a HR, and N. glutinosa was found to be resistant against race 1
      Verticillium dahliae. We furthermore report the establishment of virus-induced
      gene silencing in N. tabacum for functional analysis of Ve1 signaling.
      Collectively, our data show that N. tabacum can be used as a model plant to study
      Ve1-mediated immune signaling.

PMID- 22991999
TI  - Insights into the noncoding RNome of nitrogen-fixing endosymbiotic alpha
      proteobacteria.
AB  - Symbiotic chronic infection of legumes by rhizobia involves transition of
      invading bacteria from a free-living environment in soil to an intracellular
      state as differentiated nitrogen-fixing bacteroids within the nodules elicited in
      the host plant. The adaptive flexibility demanded by this complex lifestyle is
      likely facilitated by the large set of regulatory proteins encoded by rhizobial
      genomes. However, proteins are not the only relevant players in the regulation of
      gene expression in bacteria. Large-scale high-throughput analysis of prokaryotic
      genomes is evidencing the expression of an unexpected plethora of small
      untranslated transcripts (sRNAs) with housekeeping or regulatory roles. sRNAs
      mostly act in response to environmental cues as post-transcriptional regulators
      of gene expression through protein-assisted base-pairing interactions with target
      mRNAs. Riboregulation contributes to fine-tune a wide range of bacterial
      processes which, in intracellular animal pathogens, largely compromise virulence
      traits. Here, we summarize the incipient knowledge about the noncoding RNome
      structure of nitrogen-fixing endosymbiotic bacteria as inferred from genome-wide
      searches for sRNA genes in the alfalfa partner Sinorhizobium meliloti and further
      comparative genomics analysis. The biology of relevant S. meliloti RNA chaperones
      (e.g., Hfq) is also reviewed as a first global indicator of the impact of
      riboregulation in the establishment of the symbiotic interaction.

PMID- 22992000
TI  - Gibberellin 20-oxidase gene OsGA20ox3 regulates plant stature and disease
      development in rice.
AB  - Gibberellin (GA) 20-oxidase (GA20ox) catalyses consecutive steps of oxidation in
      the late part of the GA biosynthetic pathway. A T-DNA insertion mutant (17S-14)
      in rice, with an elongated phenotype, was isolated. Analysis of the flanking
      sequences of the T-DNA insertion site revealed that an incomplete T-DNA
      integration resulted in enhanced constitutively expression of downstream
      OsGA20ox3 in the mutant. The accumulation of bioactive GA(1) and GA(4) were
      increased in the mutant in comparison with the wild-type plant. Transgenic plants
      overexpressing OsGA20ox3 showed phenotypes similar to those of the 17S-14 mutant,
      and the RNA interference (RNAi) lines that had decreased OsGA20ox3 expression
      exhibited a semidwarf phenotype. Expression of OsGA20ox3 was detected in the
      leaves and roots of young seedlings, immature panicles, anthers, and pollens,
      based on beta-glucuronidase (GUS) activity staining in transgenic plants
      expressing the OsGA20ox3 promoter fused to the GUS gene. The OsGA20ox3 RNAi lines
      showed enhanced resistance against rice pathogens Magnaporthe oryzae (causing
      rice blast) and Xanthomonas oryzae pv. oryzae (causing bacterial blight) and
      increased expression of defense-related genes. Conversely, OsGA20ox3
      overexpressing plants were more susceptible to these pathogens comparing with the
      wild-type plants. The susceptibility of wild-type plants to X. oryzae pv. oryzae
      was increased by exogenous application of GA(3) and decreased by S-3307
      treatment. Together, the results provide direct evidence for a critical role of
      OsGA20ox3 in regulating not only plant stature but also disease resistance in
      rice.

PMID- 22992001
TI  - Multiple phytohormone signals control the transcriptional response to soybean
      aphid infestation in susceptible and resistant soybean plants.
AB  - The soybean aphid (Aphis glycines) is a major phloem-feeding pest of soybean
      (Glycine max). A. glycines feeding can cause the diversion of photosynthates and
      transmission of plant viruses, resulting in significant yield losses. In this
      study, we used oligonucleotide microarrays to characterize the long-term
      transcriptional response to soybean aphid colonization of two related soybean
      cultivars, one with the Rag1 aphid-resistance gene and one aphid-susceptible
      cultivar (without Rag1). Transcriptome profiles were determined after 1 and 7
      days of aphid infestation. Our results revealed a susceptible response involving
      hundreds of transcripts, whereas only one transcript changed in the resistant
      response to aphids. This nonexistent resistance response might be explained by
      the fact that many defense-related transcripts are constitutively expressed in
      resistant plants, whereas these same genes are activated in susceptible plants
      only during aphid infestation. Analysis of phytohormone-related transcripts in
      the susceptible response showed different hormone profiles for the two time
      points, and suggest that aphids are able to suppress hormone signals in
      susceptible plants. A significant activation of abscissic acid, normally
      associated with abiotic stress responses, at day 7, might be a decoy strategy
      implemented by the aphid to suppress effective salicylic acid- and jasmonate
      related defenses.

PMID- 22992002
TI  - The effect of anti-TNF-alpha vs. DMARDs on fatigue in rheumatoid arthritis
      patients.
AB  - OBJECTIVES: Fatigue is experienced frequently by patients with rheumatoid
      arthritis (RA). Fatigue may be caused by high levels of pain and disease activity
      in RA but can remain present while disease activity is moderate to low. It is not
      clear whether RA patients receiving anti-tumour necrosis factor (TNF) treatment
      reach lower levels of acute fatigue than RA patients receiving disease-modifying
      anti-rheumatic drug (DMARD) treatment. The aim of our study was to analyse
      whether, in patients with RA, the effect of anti-TNF on fatigue is greater than
      the effect of DMARD treatment. METHOD: Sixty-seven RA patients receiving anti-TNF
      treatment and 104 RA patients receiving DMARDs were included. All patients were
      on stable treatment for at least 6 months prior to baseline measurement. Fatigue
      was measured monthly over 1 year with the fatigue severity subscale of the
      Checklist Individual Strength (CIS-fatigue). The association between persistent
      severe fatigue and medication group was analysed using multiple linear regression
      including confounders. RESULTS: In the anti-TNF group the mean (SD) level of
      persistent fatigue was significantly higher than in the DMARD group [32.2 (11.4)
      vs. 28.3 (10.9), p = 0.025] and more patients experienced persistent severe (CIS
      fatigue score >= 35) fatigue (42% and 27% respectively, p = 0.043). However, when
      correcting for age, disease activity, haemoglobin, treatment duration, pain,
      physical disability, and clinical depression, medication type seemed to influence
      neither the mean level of persistent fatigue (p = 0.251) nor the percentage of
      patients with persistent severe fatigue (p = 0.745). CONCLUSIONS: When taking
      into account probable confounders including disease activity, medication type did
      not influence persistent fatigue in RA patients. It seems that, besides its anti
      inflammatory effect, anti-TNF has no complementary effect on persistent fatigue.

PMID- 22992004
TI  - Retraction - Horizon scanning for novel therapeutics for the treatment of
      prostate cancer.

PMID- 22992005
TI  - Synthesis of pentafluorinated beta-hydroxy ketones.
AB  - The LHMDS-promoted in situ generation of difluoroenolates from readily available
      1-aryl and 1-alkyl 2,2,4,4,4-pentafluorobutan-1,3-dione hydrates has been used to
      produce a series of pentafluorinated beta-hydroxy ketones in up to 95% yield. The
      reaction proceeds under mild conditions, tolerates a wide range of functional
      groups, and is complete within 10 min. Reduction toward the corresponding 1,3
      diol with DIBAL gives quantitative amounts and favors the formation of the syn
      isomer.

PMID- 22992006
TI  - An optical nano-antenna system design for radio therapeutic use.
AB  - This paper proposes a nano-antenna system using the optical spins generated by a
      PANDA ring resonator for radio therapeutic applications. Initially, the magnetic
      field is induced by the coupling effects between aluminium plate (Al) and TE and
      TM light modes. The generated electromagnetic wave radiation is controlled by a
      soliton power, coupling coefficients, and ring radii within the system, where
      finally the near field radio wave is transmitted to the required therapeutic
      target (neural cells). Simulation results have shown that the temperature within
      the range from 40 degrees C to about 46 degrees C can be controlled and achieved.

PMID- 22992007
TI  - Tandem semipinacol-type 1,2-carbon migration/aldol reaction toward the
      construction of [5-6-7] all-carbon tricyclic core of Calyciphylline A-type
      alkaloids.
AB  - A Lewis acid promoted tandem semipinacol-type 1,2-carbon migration/aldol reaction
      of trimethylsilane-protected vinylogous alpha-ketols with aldehyde or dimethyl
      acetals is reported. This reaction provides a direct and rapid way for the
      construction of 6-substituted spiro[4.5]decanes which extensively exist in
      Daphniphyllum alkaloids. By the use of this method, further construction of a [5
      6-7] all-carbon tricyclic core of Calyciphylline A-type alkaloids was also
      completed.

PMID- 22992008
TI  - Quantification of protein-ligand dissociation kinetics in heterogeneous affinity
      assays.
AB  - Biochemical affinity assays inherently involve interactions of heterogeneous
      nature. We report a methodology to discriminate between and accurately
      characterize specific and nonspecific interactions in force-induced dissociation
      assays. Ligand-coupled superparamagnetic particles are incubated on surfaces
      coated with a mixture of specific receptors and nonspecifically interacting
      proteins. Consequently, a mixed population of surface bound particles is formed
      with different binding natures. Magnetic field gradients are used to apply
      translational forces on the bound particles. Using a multicomponent dissociation
      analysis, we are able to make a distinction between weak nonspecific
      interactions, strong nonspecific interactions, and specific interactions. We
      validate the model by comprehensive experiments in which the biochemical
      components and applied forces are varied. The low-force data yield reliable
      values for the spontaneous dissociation rates of single-molecule specific bonds,
      and at high forces, the bond barriers are modified by the applied force. The
      results generate a new perspective for applications of magnetic force affinity
      assays in studies of heterogeneous molecular biorecognition.

PMID- 22992009
TI  - Hepatoprotective and antioxidant activity of Leucas aspera against D
      galactosamine induced liver damage in rats.
AB  - CONTEXT: Whole plant of Leucas aspera (LA) Willd. (Labiatae) is traditionally
      used in Siddha medicine for hepatic ailments. OBJECTIVE: LA was investigated for
      its hepatoprotective, antioxidant, and protective effect on microsomal drug
      metabolizing enzymes (MDMEs). MATERIALS AND METHODS: LA aqueous extract (200 and
      400 mg/kg, p.o.) was evaluated for its hepatoprotective and antioxidant activity
      in d-galactosamine (D-GalN)-induced hepatotoxicity in rats. Biochemical and
      histopathological studies were performed to assess hepatoprotective activity.
      Hexobarbitone-induced sleeping time model was used to study the protective effect
      of LA on MDMEs. RESULTS: D-GalN administration induced hepatotoxicity in rats
      which was manifested by increased levels of alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, total cholesterol, triglycerides, total
      bilirubin and oxidative stress. Pretreatment with LA extract significantly
      protected the liver in D-GalN administered rats. LA extract significantly
      elevated antioxidant enzymes like superoxide dismutase, catalase, glutathione
      peroxidase and decreased lipid peroxidation levels in liver. The total phenolic
      and flavonoid content in LA aqueous extract was found to be 28.33 +/- 0.19 gallic
      acid equivalents mg/g of extract and 3.96 +/- 0.57 rutin equivalent mg/g of
      extract, respectively. LA extract (200 and 400 mg/Kg) treatment with CCl4
      decreased the hexobarbitone-induced sleeping time in mice by 56.67 and 71.30%,
      respectively, which indicated the protective effect of LA on hepatic MDMEs.
      Histological studies showed that LA at 400 mg/kg attenuated the hepatocellular
      necrosis in D-GalN intoxicated rats. CONCLUSION: Our results contribute towards
      validation of the traditional use of LA in hepatic disorders.

PMID- 22992010
TI  - Hb Filottrano [codon 120 (-A)]: a novel frameshift mutation in exon 3 of the beta
      globin gene causing dominantly inherited beta-thalassemia intermedia.
AB  - We report a novel frameshift mutation in exon 3 of the beta-globin gene, that, in
      the heterozygous state, leads to a beta-thalassemia intermedia (beta-TI)
      phenotype (marked anemia, splenomegaly, hyperbilirubinemia, jaundice, unbalanced
      synthesis of alpha/non-alpha chains in a 34-year-old Italian woman. This
      frameshift mutation, due to the deletion of the first nucleotide (-A) at codon
      120, results in a beta-globin chain that is elongated to 156 amino acid residues.
      These highly unstable abnormal chains precipitate in the erythroblasts as
      inclusion bodies, thus causing inefficient erythropoiesis and ultimately
      resulting in the observed dominant clinical phenotype.

PMID- 22992011
TI  - Infections in the time of war--no antibiotic but a vapour box.

PMID- 22992012
TI  - The role of cytokines in cardiovascular disease in menopause.
AB  - Various studies suggest that increased levels of pro-inflammatory cytokines play
      a key role in the declining ovarian function and the resulting complications
      associated with menopause. In this review article, the authors outline the role
      of pro- and anti-inflammatory cytokines in cardiovascular disease during
      menopause.

PMID- 22992014
TI  - Nitrogen-doped fullerene as a potential catalyst for hydrogen fuel cells.
AB  - We examine the possibility of nitrogen-doped C60 fullerene (N-C60) as a cathode
      catalyst for hydrogen fuel cells. We use first-principles spin-polarized density
      functional theory calculations to simulate the electrocatalytic reactions on N
      C60. The first-principles results show that an O2 molecule can be adsorbed and
      partially reduced on the N-C complex sites (Pauling sites) of N-C60 without any
      activation barrier. Through a direct pathway, the partially reduced O2 can
      further react with H(+) and additional electrons and complete the water formation
      reaction (WFR) with no activation energy barrier. In the indirect pathway,
      reduced O2 reacts with H(+) and additional electrons to form H2O molecules
      through a transition state (TS) with a small activation barrier (0.22-0.37 eV).
      From an intermediate state to a TS, H(+) can obtain a kinetic energy of ~0.95
      3.68 eV, due to the Coulomb electric interaction, and easily overcome the
      activation energy barrier during the WFR. The full catalytic reaction cycles can
      be completed energetically, and N-C60 fullerene recovers to its original
      structure for the next catalytic reaction cycle. N-C60 fullerene is a potential
      cathode catalyst for hydrogen fuel cells.

PMID- 22992013
TI  - Optimized hyaluronic acid-hydrogel design and culture conditions for preservation
      of mesenchymal stem cell properties.
AB  - A novel approach that preserved most mesenchymal stem cell (MSC) characteristics
      was developed using MSC encapsulation in a hydrogel based on hyaluronic acid
      (HA). An optimized HA-hydrogel composition, whose characteristics were assessed
      by scanning electron microscopy and viscoelastic property analyses, as well as
      the more favorable MSC seeding density, was established. These optimal three
      dimensional MSC culture conditions allowed morphological cell remodeling,
      maintained the expression of stem cell markers over 28 days of culture, and
      preserved MSC differentiation plasticity. In addition, MSCs in HA-hydrogel
      submitted for 7 days to mechanical constraint that aimed at mimicking in vivo
      cardiac beat displayed enhanced cell survival by more than 40% compared to static
      culture conditions. Thus, the optimized HA-based hydrogel provides a niche for
      MSCs, which preserves their properties and opens ways for cell therapy, in
      particular in aortic repair medicine.

PMID- 22992015
TI  - Direct-write patterning of bacterial cells by dip-pen nanolithography.
AB  - The ability of dip-pen nanolithography (DPN) to generate nano- or microarrays of
      soft or hard materials (e.g., small molecules, DNA, proteins, nanoparticles,
      sols, and polymers) in a direct-write manner has been widely demonstrated. The
      transporting of large-sized ink materials such as bacteria, however, remains a
      significant challenge with this technique. The size limitation of the water
      meniscus formed between the DPN tip and the solid surface becomes a bottleneck in
      such diffusion-based molecular transport experiments. Herein, we report a
      straightforward "stamp-on" DPN method that uses a nanostructured poly(2-methyl-2
      oxazoline) hydrogel-coated tip and carrier agents to generate patterns of
      micrometer-sized  Escherichia coli  JM 109 bacterial cells. We demonstrate that
      this approach enables the deposition of a single bacterial cell array on a solid
      surface or arrays of layers of multiple cells by modulating the viscosity of the
      "ink" solution. Fluorescence microscopy images indicated that the deposited
      bacterial cells were kept alive on Luria-Bertani-agar layered solid surfaces
      after DPN patterning.

PMID- 22992016
TI  - Exploratory findings of audiometry in adult patients with otitis media with high
      pepsinogen concentrations: a preliminary study.
AB  - CONCLUSIONS: The present study showed that elevation of bone-conduction (BC)
      thresholds at low frequencies might be a characteristic audiometric finding in
      cases with otitis media with effusion (OME) with high pepsinogen (PG)
      concentrations. OBJECTIVE: The objective of this study was to investigate whether
      there is any characteristic audiometric finding in adult cases with otitis media
      with high PG compared to those with low PG. METHODS: Twenty-four adult patients
      with unilateral OME of undetermined etiology and high PG concentrations (> 500
      ng/ml) in their middle ear effusions (high PG group) were selected. The air
      conduction and BC thresholds of pure tone audiometry were compared between the
      affected and healthy ears. Results were compared to those in 23 patients with low
      PG concentrations (< 50 ng/ml; low PG group). RESULTS: The average BC difference
      in the threshold at 0.25 kHz between the affected ear and the healthy ear was
      significantly higher in the high PG group than in the low PG group, with a
      significantly higher proportion of patients in the high PG group having BC
      thresholds at 0.25 kHz in the affected ear that were >= 15 dB higher than in the
      healthy ear.

PMID- 22992017
TI  - Effect of surface wettability on ion-specific protein adsorption.
AB  - We have systematically investigated the effect of surface wettability on ion
      specific adsorption of bovine serum albumin (BSA) by using quartz crystal
      microbalance with dissipation (QCM-D) and surface plasmon resonance (SPR). The
      changes in frequency (Deltaf) and resonance unit (DeltaRU) show a nonmonotonous
      change of the adsorbed amount of BSA as a function of molar fraction of 1
      dodecanethiol (x(DDT)) of the self-assembled monolayer at pH 3.8, while the
      amount of adsorbed protein gradually increases with the x(DDT) at pH 7.4. The
      small changes of dissipation (DeltaD) indicate that BSA molecules form a quite
      rigid protein layer on the surfaces, which results in only a slight difference in
      the adsorbed mass between the mass-uptake estimations from the Sauerbrey equation
      and the Voigt model. The difference in the adsorbed mass between QCM-D and SPR
      measurements is attributed to the coupled water in the protein layer. On the
      other hand, specific anion effect is observed in the BSA adsorption at pH 3.8
      with the exception of the surface at x(DDT) of 0%, but no obvious cation
      specificity can be observed at pH 7.4. The DeltaD-Deltaf plots show that the BSA
      adsorption at pH 3.8 has two distinct kinetic processes. The first one dominated
      by the protein-surface interactions is an anion-nonspecific process, whereas the
      second one dominated by the protein structural rearrangements is an anion
      specific process. At pH 7.4, the second kinetic process can only be observed at
      the relatively hydrophobic surfaces, and no cation specificity is observed in the
      first and second kinetic processes.

PMID- 22992018
TI  - Metabolism of inorganic arsenic in intestinal epithelial cell lines.
AB  - This study evaluates the metabolism of inorganic arsenic (iAs) [As(III) and
      As(V)] in human intestinal cells as a function of cell type, differentiation
      stage, type of support used for cell growth, and exposure time. Additionally,
      mRNA expression of arsenic (+3 oxidation state) methyltransferase (AS3MT) was
      evaluated. For this purpose, Caco-2 (absorptive type) and HT29-MTX (goblet type)
      cells were exposed at various stages of differentiation (5, 15, and 21 days post
      seeding) with different concentrations of As(III) and As(V) (1 and 10 MUM) and
      exposure times (24, 48, and 72 h), using multiwell plates or Transwells. The
      results show that both cell lines express AS3MT at all stages of differentiation
      and in all culture conditions. Caco-2 cells are capable of metabolizing iAs,
      As(III) metabolism being greater than that observed for As(V). Metabolism depends
      on the stage of differentiation, reaching 36% after 48 h of exposure of
      differentiated cells (15 days post-seeding), with the monomethylated species as
      the major metabolite. Analysis of the cell interior shows that the metabolites
      are present predominantly in trivalent form. The type of support is also an
      important factor, metabolism being greater in multiwell plates than in Transwells
      (36 +/- 6% vs 11 +/- 3%). Neither monomethylated arsenic species (MMA) nor
      dimethylated arsenic species (DMA) are detected in HT29-MTX cells after exposure
      to iAs, possibly because most of the iAs is retained in the mucus layer and does
      not internalize. These results show that the intestine is an organ that may take
      part in presystemic metabolism of iAs. Moreover, the transformation of iAs into
      more toxic species indicates the need to study the effects of this species on the
      intestinal epithelium.

PMID- 22992019
TI  - Prevalence and determinants of extrapulmonary involvement in patients with
      pulmonary tuberculosis in a Sub-Saharan African country: a cross-sectional study.
AB  - BACKGROUND: Determinants of extrapulmonary involvement during pulmonary
      tuberculosis (PTB) have not been extensively investigated. We assessed the
      prevalence and determinants of extrapulmonary involvement during PTB in a Sub
      Saharan African country with a high prevalence of both TB and human
      immunodeficiency virus (HIV) infection. METHODS: The medical records of patients
      aged >= 15 y, admitted for a first episode of TB to the Pneumology Service of
      Yaounde Jamot Hospital, Cameroon, between 2009 and 2010 were considered.
      Determinants of extrapulmonary involvement were investigated through logistic
      regression. RESULTS: A total of 984 patients (58.9% male), with a median age
      (25(th)-75(th) percentiles) of 32 (25-41) y were admitted for a first episode of
      TB, including 629 (63.9%) with isolated PTB, 127 (12.9%) with isolated
      extrapulmonary TB (EPTB), and 228 (23.2%) with both PTB and EPTB (PTB/EPTB).
      Therefore, the prevalence of EPTB among those with PTB was 26.6% (228/857). The
      main determinants of EPTB among patients with PTB were male sex (adjusted odds
      ratio (OR) 2.71, 95% confidence interval (95% CI) 1.71-4.03), HIV infection (OR
      2.20, 95% CI 1.36-3.55), absence of fibrotic lung lesions (OR 1.96, 95% CI 1.23
      3.14), smear-negative PTB (OR 7.20, 95% CI 4.13-12.56), anaemia (OR 1.60, 95% CI
      1.03-2.50), and leukopenia (OR 2.59, 95% CI 1.12-5.98). CONCLUSIONS: About a
      quarter of patients with PTB in this setting also have extrapulmonary
      involvement. EPTB is less contagious, less frequent than PTB, and less well
      addressed by programs in developing countries, while its identification is
      important for optimizing care. The presence of determinants of EPTB among
      patients with PTB should motivate active investigation of extrapulmonary
      involvement in order to improve management.

PMID- 22992020
TI  - Ferroportin expression in haem oxygenase 1-deficient mice.
AB  - HO1 (haem oxygenase 1) and Fpn (ferroportin) are key proteins for iron recycling
      from senescent red blood cells and therefore play a major role in controlling the
      bioavailability of iron for erythropoiesis. Although important aspects of iron
      metabolism in HO1-deficient (Hmox1-/-) mice have already been revealed, little is
      known about the regulation of Fpn expression and its role in HO1 deficiency. In
      the present study, we characterize the cellular and systemic factors influencing
      Fpn expression in Hmox1-/- bone marrow-derived macrophages and in the liver and
      kidney of Hmox1-/- mice. In Hmox1-/- macrophages, Fpn protein was relatively
      highly expressed under high levels of hepcidin in culture medium. Similarly,
      despite high hepatic hepcidin expression, Fpn is still detected in Kupffer cells
      and is also markedly enhanced at the basolateral membrane of the renal tubules of
      Hmox1-/- mice. Through the activity of highly expressed Fpn, epithelial cells of
      the renal tubules probably take over the function of impaired system of tissue
      macrophages in recycling iron accumulated in the kidney. Moreover, although we
      have found increased expression of FLVCR (feline leukaemia virus subgroup C
      receptor), a haem exporter, in the kidneys of Hmox1-/- mice, haem level was
      increased in these organs. Furthermore, we show that iron/haem-mediated toxicity
      are responsible for renal injury documented in the kidneys of Hmox1-/- mice.

PMID- 22992021
TI  - Proliferation signal inhibitor toxicities after thoracic transplantation.
AB  - INTRODUCTION: Thoracic transplantation represents the definitive therapy for end
      stage lung and heart diseases. Over the life of the allograft, upregulation of
      profibroproliferative mechanisms result in the advancement of chronic rejection.
      These take the form of bronchiolitis obliterans syndrome (BOS) in a lung
      recipient and cardiac allograft vasculopathy (CAV) in a heart recipient. The
      proliferation signal inhibitors (PSI), sirolimus and everolimus, represent a
      therapeutic option to downregulate this fibroproliferative effect. Additionally,
      these drugs may result in renal sparing and express potent anti-viral activity.
      However, they are fraught with substantial and complex toxicities that limit
      their use. AREAS COVERED: In this review, the authors first describe the
      mechanism of immunosuppression and pharmacokinetics of the PSIs. Subsequently,
      their use in thoracic transplant recipients for the purposes of renal sparing,
      anti-cytomegalovirus effect, and antifibroproliferative effects to prolong the
      onset or arrest progression of BOS and CAV are reviewed. The toxicities
      associated with PSI use are described, and three areas are focused on in detail:
      nephrotoxicities, wound healing impairment, and pulmonary toxicities. Finally,
      the authors summarize the patients in whom PSI use may be advantageous while
      minimizing potential toxicities. EXPERT OPINION: The potential benefits of PSI
      use in thoracic transplantation make their use attractive. Relative to
      alternative antiproliferatives, such as mycophenolate or azathioprine, PSI
      treated patients experience significantly more serious adverse effects and
      discontinue treatment significantly more often. It is critical that patients be
      wisely selected for PSI use in an effort to minimize toxicities.

PMID- 22992022
TI  - Team-based learning: from educational theory to emotional intelligence.

PMID- 22992023
TI  - The contribution of international medical students to Taiwanese medical school
      classes.

PMID- 22992024
TI  - Synthesis, evaluation, and radiolabeling of new potent positive allosteric
      modulators of the metabotropic glutamate receptor 2 as potential tracers for
      positron emission tomography imaging.
AB  - The synthesis and in vitro and in vivo evaluation of a new series of 7
      (phenylpiperidinyl)-1,2,4-triazolo[4,3-a]pyridines, which were conveniently
      radiolabeled with carbon-11, as potential positron emission tomography (PET)
      radiotracers for in vivo imaging of the allosteric binding site of the
      metabotropic glutamate (mGlu) receptor subtype 2 are described. The synthesized
      compounds proved to be potent and selective positive allosteric modulators (PAMs)
      of the mGlu receptor 2 (mGluR2) in a [35S]GTPgammaS binding assay and were able
      to displace an mGluR2 PAM radioligand, which we had previously developed, with
      IC50 values in the low nanomolar range. The most promising candidates were
      radiolabeled and subjected to biodistribution studies and radiometabolite
      analysis in rats. Preliminary small-animal PET (MUPET) studies in rats indicated
      that [11C]20f binds specifically and reversibly to an mGluR2 allosteric site,
      strongly suggesting that it is a promising candidate for PET imaging of mGluR2 in
      the brain.

PMID- 22992025
TI  - Giant cell arteritis presenting with a lateral medullary stroke in a patient with
      multiple atherosclerotic risk factors.

PMID- 22992026
TI  - A phenomenological approach to psychoprosthetics.
AB  - The phenomenology of human embodiment can advance the practitioner's
      understanding of the lived human body and in particular, what it means to
      incorporate a prosthetic device into one's body. In order for a prosthesis to be
      incorporated into the lived body of the patient, the prosthesis must arguably be
      integrated into the body schema. This article uses the phenomenology of Maurice
      Merleau-Ponty and others to identify three of the necessary conditions of
      embodiment that determine the body schema: corporeal understanding, transparency
      and sensorimotor feedback. It then examines the structure of each of these
      conditions of embodiment and how they impact the lived body's incorporation of
      prostheses and other artifacts. [Box: see text].

PMID- 22992028
TI  - Physician detection of unhealthy substance use on inpatient teaching and
      hospitalist medical services.
AB  - BACKGROUND: Screening, brief intervention, and referral to treatment for
      substance use depends on reliable identification. The goal of this study was to
      determine the rate of detection of unhealthy substance use by physicians on
      teaching and nonteaching medical services at a community teaching hospital.
      METHODS: This cross-sectional study was conducted from February to June 2009. All
      new medicine admissions to the Teaching Service or the nonteaching Hospitalist
      Service were assessed for unhealthy substance use using the Alcohol Use Disorders
      Identification Test-Consumption (AUDIT-C) and Drug Abuse Screening Test (DAST).
      All patients identified with substance use completed the Alcohol, Smoking, and
      Substance Involvement Screening Test (ASSIST). Medical record review was also
      performed to assess physician documentation. RESULTS: Of 442 eligible patients,
      414 consented to participate. Patients on the Teaching Service were more likely
      to be male, younger, unmarried, non-white, uninsured or receiving publicly funded
      insurance, and current smokers (p < .01 for all comparisons). Overall, the
      detection rate for unhealthy substance use was 64.3% (63 of 98 confirmed cases),
      with service-specific rates of 73.4% for the Teaching Service, compared with
      47.1% for the Hospitalist Service (p = .011). ICD-9 coding accounted for 53.1% of
      identified cases on the Teaching Service and 14.7% of identified cases on the
      Hospitalist Service (p < .001). Assignment to the Hospitalist Service, being
      married, and isolated unhealthy drug use were independently associated with
      decreased physician detection rates. CONCLUSIONS: Our study suggests that
      unhealthy substance use is more likely to be detected on a Teaching Service than
      on a Hospitalist Service.

PMID- 22992027
TI  - Behavioral dynamics and neural grounding of a dynamic field theory of multi
      object tracking.
AB  - The ability to dynamically track moving objects in the environment is crucial for
      efficient interaction with the local surrounds. Here, we examined this ability in
      the context of the multi-object tracking (MOT) task. Several theories have been
      proposed to explain how people track moving objects; however, only one of these
      previous theories is implemented in a real-time process model, and there has been
      no direct contact between theories of object tracking and the growing neural
      literature using ERPs and fMRI. Here, we present a neural process model of object
      tracking that builds from a Dynamic Field Theory of spatial cognition.
      Simulations reveal that our dynamic field model captures recent behavioral data
      examining the impact of speed and tracking duration on MOT performance. Moreover,
      we show that the same model with the same trajectories and parameters can shed
      light on recent ERP results probing how people distribute attentional resources
      to targets vs. distractors. We conclude by comparing this new theory of object
      tracking to other recent accounts, and discuss how the neural grounding of the
      theory might be effectively explored in future work.

PMID- 22992029
TI  - Factors associated with reporting classic menopausal symptoms differ.
AB  - OBJECTIVES: To investigate how symptoms experienced in midlife cluster and to
      identify factors independently associated with hot flushes, night sweats, and
      vaginal dryness. METHODS: A questionnaire was sent to 8206 women aged 45-54
      years, recruited from family practices in north-east Scotland, UK. Using data
      collected about 23 symptoms, we conducted factor analysis for premenopausal,
      perimenopausal, postmenopausal and surgically menopausal women. Forward stepwise
      logistic regression was used to identify sociodemographic, lifestyle and
      psychological variables independently associated with the classic menopausal
      symptoms. RESULTS: Overall, 4407 women responded. Hot flushes were experienced by
      46.7% (95% confidence interval (CI) 45.2-48.2) of women, night sweats by 46.4%
      (95% CI 44.9-47.9) and vaginal dryness by 28.2% (95% CI 26.9-29.6). Seven factors
      including 20 symptoms emerged from factor analysis. Hot flushes were associated
      with: being perimenopausal or postmenopausal; low education; obesity; low social
      support; reporting night sweats, musculoskeletal, bloating, menstrual and sexual
      symptoms; using complementary alternative medicines, lifestyle (e.g. exercising)
      or psychological management strategies (e.g. talking to family or friends) for
      menopausal symptoms. Night sweats were associated with: lower body weight;
      smoking; possible depression; reporting sleep difficulties, hot flushes and
      sexual symptoms; using lifestyle strategies for menopausal symptoms. Vaginal
      dryness was associated with: being postmenopausal; high education; high social
      support; below average physical health, reporting hot flushes, somatic symptoms
      and decreased sexual interest; using psychological or lifestyle strategies for
      menopausal symptoms. CONCLUSION: It is important to investigate each classic
      menopausal symptom separately. Combining menopausal symptoms into categories such
      as vasomotor symptoms may lead to inaccurate conclusions about variables
      associated with these symptoms.

PMID- 22992030
TI  - Steady-state voltammetry of a microelectrode in a closed bipolar cell.
AB  - Here we report the theory and experimental study of the steady-state voltammetric
      behavior of a microelectrode used as a limiting pole in a closed bipolar
      electrochemical cell. We show that the steady-state voltammetric response of a
      microelectrode used in a closed bipolar cell can be quantitatively understood by
      considering the responses of both poles in their respective conventional two
      electrode setups. In comparison to a conventional electrochemical cell, the
      voltammetric response of the bipolar cell has a similar sigmoidal shape and
      limiting current; however, the response is often slower than that of the typical
      two-electrode setup. This leads to a broader voltammogram and a decreased wave
      slope, which can be somewhat misleading, causing the appearance that the process
      being studied is irreversible when it instead can be a result of the coupling of
      two reversible processes. We show that a large limiting current on the excess
      pole would facilitate the observation of a faster voltammetric response and that
      both redox concentration and electrode area of the excess pole affect the wave
      shape. Both factors should be maximized in electroanalytical experiments in order
      to obtain fast voltammetric responses on the main electrode of interest and to
      detect quick changes in analyte concentrations.

PMID- 22992031
TI  - Effects of shark cartilage polysaccharides on the secretion of IL-6 and IL-12 in
      rheumatoid arthritis.
AB  - CONTEXT: Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by
      inflammation of the synovial membrane, leading to articular cartilage
      destruction. Shark cartilage polysaccharide (SCP) is a biodegradable,
      biocompatible, nontoxic, non-immunogenic and non-inflammatory polysaccharide that
      may be used in treating RA. OBJECTIVE: The anti-RA activities of SCP given orally
      to rats are investigated here for the first time. MATERIALS AND METHODS: SCP
      treatment group were administered with SCP-1, SCP-2 in the dosage of 9 mg/day for
      24 days. The effect of SCP-1 and SCP-2 on the body weight, paw swelling,
      morphological changes of ankle and IL-6, IL-12 secretion in RA rats are examined.
      RESULTS: On day 24, there were no obvious differences in BMI between positive,
      SCP-1 and SCP-2 group. The swelling degree of SCP-1 and SCP-2 group was less
      serious than model group. X-ray revealed that SCP-1, SCP-2 group owned normal
      joint alignment and more smooth and tidy articular surface. The SCP-1 and SCP-2
      have inhibitory effect on IL-6 (430.3 +/- 25.6 pg/mL, 439.1 +/- 35.9 pg/mL) and
      IL-12 (63.9 +/- 20.1 pg/mL, 64.9 +/- 14.1 pg/mL) secretion, which showed
      significant differences with model group (612 +/- 72.3 pg/mL, 230.1 +/- 29.2
      pg/mL), but still higher than normal group (361.8 +/- 47.1 pg/mL, 34.2 +/- 15.1
      pg/mL) and lower than positive group (418.1 +/- 42.5 pg/mL, 90.2 +/- 17.8 pg/mL).
      Especially, when the concentration of SCP was 125 MUg/mL, the contents of IL-6
      (431.1 +/- 43.3 pg/mL, 401.7 +/- 55.7 pg/mL) and IL-12 (63.2 +/- 12.3 pg/mL, 52.3
      +/- 8.7 pg/mL) were lowest. DISCUSSION AND CONCLUSION: These findings demonstrate
      that SCP have excellent anti-RA activities and thus have great potential as a
      drug for treating RA diseases.

PMID- 22992032
TI  - Molecular diversity associated with the dissemination of CTX-M-15 beta-lactamase
      gene in blood culture isolates of Escherichia coli from Edinburgh.
AB  - BACKGROUND: Escherichia coli producing the CTX-M-15 beta-lactamase are a major
      cause of infection. We present the characterization of plasmids encoding the CTX
      M-15 beta-lactamase gene, the genetic environment, and the mode of spread of this
      gene in blood culture isolates from a single hospital. METHODS: Blood culture E.
      coli isolates with extended spectrum beta-lactamase (ESBL) phenotype were
      screened for the presence of the bla(CTX-M) gene, other ESBLs, and aac(6')-Ib-cr
      genes. The genetic environment of bla(CTX-M) was determined by DNA sequencing.
      Plasmids were classified by their incompatibility group from polymerase chain
      reaction (PCR) replicon typing. Plasmid numbers and sizing were assessed by
      alkaline lysis and S1 nuclease digestion. Genotyping of the strains was
      determined by pulsed-field gel electrophoresis (PFGE) and ST131 by allele
      specific PCR. RESULTS: Seven isolates had bla(CTX-M-15), with these isolates
      additionally having bla(TEM) (n = 5), bla(OXA) (n = 6), and aac(6')-Ib-cr (n =
      6). Insertion sequence ISEcp1 was found upstream of the bla(CTX-M) gene, and in 2
      isolates, ISEcp1 was found to be truncated with insertion sequence IS26. Plasmid
      replicon typing showed bla(CTX-M-15) genes were carried on the IncFII plasmid.
      All 7 isolates were associated with the O25b-ST131 clone. The PFGE banding
      pattern showed only 3 isolates were able to demonstrate clonality. CONCLUSIONS:
      This study shows the molecular diversity associated with the dissemination of
      bla(CTX-M-15) in a single Scottish hospital, which is largely due to horizontal
      transfer of multi- resistance IncF plasmids rather than clonal spread. It
      demonstrates that more detailed information is needed to monitor these bacteria
      to control them appropriately.

PMID- 22992034
TI  - Monoplatinum doping of gold nanoclusters and catalytic application.
AB  - We report single-atom doping of gold nanoclusters (NCs), and its drastic effects
      on the optical, electronic, and catalytic properties, using the 25-atom system as
      a model. In our synthetic approach, a mixture of Pt(1)Au(24)(SC(2)H(4)Ph)(18) and
      Au(25)(SC(2)H(4)Ph)(18) was produced via a size-focusing process, and then
      Pt(1)Au(24)(SC(2)H(4)Ph)(18) NCs were obtained by selective decomposition of
      Au(25)(SC(2)H(4)Ph)(18) in the mixture with concentrated H(2)O(2) followed by
      purification via size-exclusion chromatography. Experimental and theoretical
      analyses confirmed that Pt(1)Au(24)(SC(2)H(4)Ph)(18) possesses a Pt-centered
      icosahedral core capped by six Au(2)(SC(2)H(4)Ph)(3) staples. The
      Pt(1)Au(24)(SC(2)H(4)Ph)(18) cluster exhibits greatly enhanced stability and
      catalytic activity relative to Au(25)(SC(2)H(4)Ph)(18) but a smaller energy gap
      (E(g) ~ 0.8 eV vs 1.3 eV for the homogold cluster).

PMID- 22992035
TI  - Uncovering molecular details of urea crystal growth in the presence of additives.
AB  - Controlling the shape of crystals is of great practical relevance in fields like
      pharmacology and fine chemistry. Here we examine the paradigmatic case of urea
      which is known to crystallize from water with a needle-like morphology. To
      prevent this undesired effect, inhibitors that selectively favor or discourage
      the growth of specific crystal faces can be used. In urea the most relevant faces
      are the {001} and the {110} which are known to grow fast and slow, respectively.
      The relevant growth speed difference between these two crystal faces is
      responsible for the needle-like structure of crystals grown in water solution. To
      prevent this effect, additives are used to slow down the growth of one face
      relative to another, thus controlling the shape of the crystal. We study the
      growth of fast {001} and slow {110} faces in water solution and the effect of
      shape controlling inhibitors like biuret. Extensive sampling through molecular
      dynamics simulations provides a microscopic picture of the growth mechanism and
      of the role of the additives. We find a continuous growth mechanism on the {001}
      face, while the slow growing {110} face evolves through a birth and spread
      process, in which the rate-determining step is the formation on the surface of a
      two-dimensional crystalline nucleus. On the {001} face, growth inhibitors like
      biuret compete with urea for the adsorption on surface lattice sites; on the
      {110} face instead additives cannot interact specifically with surface sites and
      play a marginal sterical hindrance of the crystal growth. The free energies of
      adsorption of additives and urea are evaluated with advanced simulation methods
      (well-tempered metadynamics) allowing a microscopic understanding of the
      selective effect of additives. Based on this case study, general principles for
      the understanding of the anisotropic growth of molecular crystals from solutions
      are laid out. Our work is a step toward a rational development of novel shape
      affecting additives.

PMID- 22992036
TI  - Superhydrophobicity of lotus leaves versus birds wings: different physical
      mechanisms leading to similar phenomena.
AB  - Remarkable water repellency of birds' feathers and lotus leaves is discussed. It
      is demonstrated that physical mechanisms of superhydrophobicity of birds'
      feathers and lotus leaves are very different. The topography of lotus leaves is a
      truly hierarchical one, whereas birds' feathers manifest pseudohierarchical
      relief, where various scales do not interact. The pronounced stability of the
      Cassie state observed on birds' feathers is due to the high value of critical
      pressure necessary for their total wetting, which is on the order of magnitude of
      100 kPa. This high value allows feathers to withstand large dynamical pressure of
      rain droplets and remain dry under the rain. The energy barrier separating the
      Cassie state from the complete wetting situation calculated for a feather is also
      very high, allowing the increased stability of superhydrophobicity.

PMID- 22992037
TI  - Integrating ligand-based and protein-centric virtual screening of kinase
      inhibitors using ensembles of multiple protein kinase genes and conformations.
AB  - The rapidly growing wealth of structural and functional information about kinase
      genes and kinase inhibitors that is fueled by a significant therapeutic role of
      this protein family provides a significant impetus for development of targeted
      computational screening approaches. In this work, we explore an ensemble-based,
      protein-centric approach that allows for simultaneous virtual ligand screening
      against multiple kinase genes and multiple kinase receptor conformations. We
      systematically analyze and compare the results of ligand-based and protein
      centric screening approaches using both single-receptor and ensemble-based
      docking protocols. A panel of protein kinase targets that includes ABL, EGFR,
      P38, CDK2, TK, and VEGFR2 kinases is used in this comparative analysis. By
      applying various performance metrics we have shown that ligand-centric shape
      matching can provide an effective enrichment of active compounds outperforming
      single-receptor docking screening. However, ligand-based approaches can be highly
      sensitive to the choice of inhibitor queries. Employment of multiple inhibitor
      queries combined with parallel selection ranking criteria can improve the
      performance and efficiency of ligand-based virtual screening. We also
      demonstrated that replica-exchange Monte Carlo docking with kinome-based
      ensembles of multiple crystal structures can provide a superior early enrichment
      on the kinase targets. The central finding of this study is that incorporation of
      the template-based structural information about kinase inhibitors and protein
      kinase structures in diverse functional states can significantly enhance the
      overall performance and robustness of both ligand and protein-centric screening
      strategies. The results of this study may be useful in virtual screening of
      kinase inhibitors potentially offering a beneficial spectrum of therapeutic
      activities across multiple disease states.

PMID- 22992038
TI  - Clinical experience of granulocyte transfusion in the management of neutropenic
      patients with haematological malignancies and severe infection.
AB  - BACKGROUND: Prolonged chemotherapy-induced neutropenia is a major risk factor for
      the development of severe bacterial and fungal infections. Infectious
      manifestations may progress despite adequate anti-infectious treatment and lead
      to a very high short-term mortality. Granulocyte transfusion (GT) therapy is
      often considered. However, its efficacy is not well documented. METHODS: We
      retrospectively analyzed the clinical characteristics and outcome of a cohort of
      patients with haematological malignancies receiving GT during neutropenia and
      severe infection. RESULTS: A total of 30 patients with a median age of 46 y
      (range 3-82 y) who had received 1 or more GT were included. Acute leukaemia (80%)
      and non-Hodgkin lymphoma (17%) predominated as the underlying malignancy. All
      patients had severe and prolonged (median 16 days) neutropenia. The major
      indications for GT were persistent fever and clinical deterioration despite broad
      anti-infectious therapy, in combination with progressive pneumonia (n = 16),
      neutropenic enterocolitis (n = 6), and soft tissue infections (n = 3). GTs were
      given for a median of 3 transfusions (range 1-14). The median time to fever
      defervescence after GT was 14 days (range 6-33 days). For 11 patients, the
      resolution of fever and all signs of infection could directly be related to GT,
      and 3 of these patients became long-term survivors. Mortality at 30 days post-GT
      was 40% and at 6 months post-GT was 72%. GT was well tolerated. CONCLUSIONS: A
      substantial proportion of severely ill neutropenic patients appeared to benefit
      from GT. The results further underline the need for well- designed, randomized,
      prospective trials to determine the efficacy of this intervention in patients
      with life-threatening infectious complications.

PMID- 22992039
TI  - Physiologically based kinetic models for the alkenylbenzene elemicin in rat and
      human and possible implications for risk assessment.
AB  - The present study describes physiologically based kinetic (PBK) models for the
      alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on
      the PBK models previously developed for the structurally related alkenylbenzenes
      estragole, methyleugenol, and safrole. Using the newly developed models, the
      level of metabolic activation of elemicin in rat and human was predicted to
      obtain insight in species differences in the bioactivation of elemicin and read
      across to the other methoxy allylbenzenes, estragole and methyleugenol. Results
      reveal that the differences between rat and human in the formation of the
      proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate
      carcinogenic metabolite 1'-sulfoxyelemicin are limited (<3.8-fold). In addition,
      a comparison was made between the relative importance of bioactivation for
      elemicin and that of estragole and methyleugenol. Model predictions indicate that
      compound differences in the formation of the 1'-sulfoxymetabolites are limited
      (<11-fold) in rat and human liver. The insights thus obtained were used to
      perform a risk assessment for elemicin using the margin of exposure (MOE)
      approach and read across to the other methoxy allylbenzene derivatives for which
      in vivo animal tumor data are available. This reveals that elemicin poses a lower
      priority for risk management as compared to its structurally related analogues
      estragole and methyleugenol. Altogether, the results obtained indicate that PBK
      modeling provides an important insight in the occurrence of species differences
      in the metabolic activation of elemicin. Moreover, they provide an example of how
      PBK modeling can facilitate a read across in risk assessment from compounds for
      which in vivo toxicity studies are available to a compound for which only limited
      toxicity data have been described, thus contributing to the development of
      alternatives for animal testing.

PMID- 22992040
TI  - Heavy metal staining, a comparative assessment of gadolinium chloride and osmium
      tetroxide for inner ear labyrinthine contrast enhancement using X-ray
      microtomography.
AB  - CONCLUSION: The use of both gadolinium chloride (GdCl(3)) and osmium tetroxide
      (OsO(4)) allowed for the visualization of the membranous labyrinth and other
      intralabyrinthine structures, at different intensities, as compared with the
      control sample. This initial comparison shows the advantages of GdCl(3) in
      radiological assessments and OsO(4) in more detailed anatomical studies and
      pathways of labyrinthine pathogenesis using X-ray microtomography (microCT).
      OBJECTIVE: To assess an improved OsO(4) staining protocol and compare the
      staining affinities against GdCl(3). METHODS: Guinea pig temporal bones were
      stained with either GdCl(3) (2% w/v) for 7 days or OsO(4) (2% w/v) for 3 days,
      and scanned in a microCT system. The post-scanned datasets were then assessed in
      a 3D rendering program. RESULTS: The enhanced soft tissue contrast as presented
      in the temporal bones stained with either GdCl(3) or OsO(4) allowed for the
      membranous labyrinth to be visualized throughout the whole specimen. GdCl(3)
      stained specimens presented more defined contours of the bone profile in the
      radiographs, while OsO(4)-stained specimens provided more anatomical detail of
      individual intralabyrinthine structures, hence allowing spatial relationships to
      be visualized with ease in a 3D rendering context and 2D axial slice images.

PMID- 22992041
TI  - Impact of visual internal urethrotomy on sexual function in patients with
      urethral stricture.
AB  - BACKGROUND AND PURPOSE: Visual internal urethrotomy (VIU) is an option for the
      management of urethral stricture. However, little is known regarding sexual
      function after surgery. PATIENTS AND METHODS: Seventy-six patients who underwent
      VIU were evaluated by using the Korean version of the Male Sexual Health
      Questionnaire. Three sexual functional domains of erection (EFD), satisfaction
      (SAD), and ejaculation (EjFD) were assessed at baseline, 3 months, 6 months, and
      12 months after surgery. We assessed clinical factors (age, etiology, and maximum
      flow rate) and radiologic factors (stricture site, stricture length, frequency of
      recurrence, and duration until first recurrence). We compared with each sexual
      functional domain score by age group (range: 40-49, 50-59, 60-69, and 70-79
      years). RESULTS: A total of 76 men with mean age of 57.1+/-13.07 years completed
      this study. In univariate analysis, there were significant losses of EFD scores
      at postoperative 3 months for all age groups (P<0.05). And these scores were
      regained after postoperative 6 months. There was no statistically significant
      difference in SAD. Age, length of stricture, frequency of recurrence, and
      duration until first recurrence were significant differences in EjFD (P<0.001,
      P=0.006, P=0.005, and P=0.013, respectively). In 40 to 49 and 50 to 59 age
      groups, VIU improves EjFD (P<0.001, respectively). Multiple linear regression
      analysis revealed that age and stricture length were independent factors of VIU
      on EjFD (P<0.001 and P=0.013, respectively). CONCLUSIONS: VIU can improve
      ejaculatory function in younger age group (40-59 years). Age and stricture length
      are independent predictive factors of VIU on ejaculatory function.

PMID- 22992042
TI  - Theoretical investigation into the mechanism of Au(I)-catalyzed reaction of
      alcohols with 1,5 enynes.
AB  - Density functional theory has been used to investigate the reactions of 1,5
      enynes with alcohols in the presence of a gold catalyst. We have compared the
      mechanism of the alcohol addition reaction for the enyne with that of the enyne
      where the carbon at position 3 is replaced with silicon. We find that different
      intermediates are present in both cases, and in the case of the silicon analogue,
      the intermediate that we find from the calculations is different from any that
      have previously been proposed in the literature. For the silicon analogue we have
      been able to rationalize the observed effects of alcohol concentration and
      nucleophilicity on the product distribution. For the carbon-based enyne we have
      shown why different products are observed depending on the substitution at
      position 3 of the enyne. Overall, we have provided for the first time a
      consistent explanation and rationalization of several different experiments that
      have been previously published in the literature. Our mechanism will assist in
      predicting the outcome of experimental reactions involving different alcohols,
      reagent concentrations, and substitution patterns of the 1,5 enynes.

PMID- 22992044
TI  - Quantum variational transition state theory for hydrogen tunneling in enzyme
      catalysis.
AB  - Experiments in recent years have shown that there is a large kinetic isotope
      effect in the rate of transfer of hydrogen or deuterium in enzymatic reactions of
      soybean lipoxygenase-1. The kinetic isotope effect (KIE) is only weakly
      temperature dependent but varies significantly in the presence of mutants whose
      functional groups are located rather far from the reaction center. In this paper
      we suggest that variational transition state theory as applied to dissipative
      systems, above the crossover temperature between deep tunneling and thermal
      activation, may be used as a paradigm for understanding the dynamics of these
      reactions. We find that the theory fits the experimental data rather well. The
      effects of different mutants are readily interpreted in terms of the friction
      they exert on the reaction center. Increasing the distal functional group
      increases the friction and thus lowers the kinetic isotope effect.

PMID- 22992043
TI  - Attenuated human bone morphogenetic protein-2-mediated bone regeneration in a rat
      model of composite bone and muscle injury.
AB  - Extremity injuries involving large bone defects with concomitant severe muscle
      damage are a significant clinical challenge often requiring multiple treatment
      procedures and possible amputation. Even if limb salvage is achieved, patients
      are typically left with severe short- and long-term disabilities. Current
      preclinical animal models do not adequately mimic the severity, complexity, and
      loss of limb function characteristic of these composite injuries. The objectives
      of this study were to establish a composite injury model that combines a
      critically sized segmental bone defect with an adjacent volumetric muscle loss
      injury, and then use this model to quantitatively assess human bone morphogenetic
      protein-2 (rhBMP-2)-mediated tissue regeneration and restoration of limb
      function. Surgeries were performed on rats in three experimental groups: muscle
      injury (8-mm-diameter full-thickness defect in the quadriceps), bone injury (8-mm
      nonhealing defect in the femur), or composite injury combining the bone and
      muscle defects. Bone defects were treated with 2 MUg of rhBMP-2 delivered in the
      pregelled alginate injected into a cylindrical perforated nanofiber mesh. Bone
      regeneration was quantitatively assessed using microcomputed tomography, and limb
      function was assessed using gait analysis and muscle strength measurements. At 12
      weeks postsurgery, treated bone defects without volumetric muscle loss were
      consistently bridged. In contrast, the volume and mechanical strength of
      regenerated bone were attenuated by 45% and 58%, respectively, in the identically
      treated composite injury group. At the same time point, normalized muscle
      strength was reduced by 51% in the composite injury group compared to either
      single injury group. At 2 weeks, the gait function was impaired in all injury
      groups compared to baseline with the composite injury group displaying the
      greatest functional deficit. We conclude that sustained delivery of rhBMP-2 at a
      dose sufficient to induce bridging of large segmental bone defects failed to
      promote regeneration when challenged with concomitant muscle injury. This model
      provides a platform with which to assess bone and muscle interactions during
      repair and to rigorously test the efficacy of tissue engineering approaches to
      promote healing in multiple tissues. Such interventions may minimize
      complications and the number of surgical procedures in limb salvage operations,
      ultimately improving the clinical outcome.

PMID- 22992045
TI  - Effective seroconversion and safety following the pandemic influenza vaccination
      (anti-H1N1) in patients with juvenile idiopathic arthritis.
AB  - OBJECTIVES: To assess the vaccine response in juvenile idiopathic arthritis (JIA)
      as an extension of previous observation of immunogenicity and safety of a non
      adjuvanted influenza A H1N1/2009 vaccine in a large population of juvenile
      rheumatic diseases. Moreover, to assess the possible influence of demographic
      data, disease subtypes, disease activity, and treatment on immunogenicity and the
      potential deleterious effect of the vaccine in the disease itself, particularly
      in the number of arthritis and inflammatory markers. METHODS: A total of 95
      patients with JIA and 91 healthy controls were evaluated before and 21 days after
      vaccination, and serology for anti-H1N1 was performed by haemagglutination
      inhibition assay (HIA). Patient and physician visual analogue scales (VAS),
      Childhood Health Assessment Questionnaire (CHAQ), number of active joints, acute
      phase reactants, and treatments were evaluated before and after vaccination.
      Adverse events were also reported. RESULTS: JIA patients and controls were
      comparable regarding mean current age (14.9 +/- 3.2 vs. 14.6 +/- 3.7 years, p =
      0.182). After vaccination, the seroconversion rate was significantly lower in JIA
      patients compared to controls (83.2% vs. 95.6%, p = 0.008), particularly in the
      polyarticular subtype (80% vs. 95.6%, p = 0.0098). Of note, JIA subtypes, number
      of active joints, acute phase reactants, CHAQ, patient and physician VAS, and use
      of disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive drugs were
      similar between seroconverted and non-seroconverted patients (p > 0.05).
      Regarding vaccine safety, no deterioration was observed in the number of active
      joints and acute phase reactants during the study period. CONCLUSION: Influenza A
      H1N1/2009 vaccination in JIA induces a lower but effective protective antibody
      response probably independent of disease parameters and treatment with an
      adequate disease safety profile.

PMID- 22992046
TI  - Synthesis of PS/Ag nanocomposite spheres with catalytic and antibacterial
      activities.
AB  - This paper describes a simple, mild, and environmentally friendly approach to
      synthesize polystyrene/Ag (PS/Ag) nanocomposite spheres, which makes use of both
      reducing and stabilizing functions of polyvinylpyrrolidone (PVP) in aqueous
      media. In this approach, monodisperse polystyrene (PS) spheres, which are used as
      templates for the synthesis of core-shell nanocomposite spheres, are sulfonated
      first. Then, [Ag(NH(3))(2)](+) ions are adsorbed onto the surface of the PS
      template spheres via electrostatic attraction between -SO(3)H groups (grafted on
      the surface of the PS template spheres) and [Ag(NH(3))(2)](+) ions.
      [Ag(NH(3))(2)](+) ions are then reduced by and simultaneously protected by PVP.
      In this way, the PS/Ag nanocomposite spheres in aqueous media are obtained
      through a so-called one-pot method. Neither additional reducing agents nor toxic
      organic solvents are utilized during the synthesis process. Furthermore, the
      coverage degree and the particle size of Ag nanoparticles on PS/Ag nanocomposite
      spheres is easily tuned by changing the concentration of [Ag(NH(3))(2)](+) ions
      in aqueous media. Moreover, these PS/Ag nanocomposite spheres can be used as
      catalyst for the reduction of organic dyes and as antibacterial agents against
      Salmonella and Escherichia coli. In the present study, these PS/Ag nanocomposite
      spheres exhibit excellent catalytic properties (both in efficiency and
      recyclability) for the reduction of organic dyes, and the preliminary
      antibacterial assays indicate that these PS/Ag nanocomposite spheres also possess
      extraordinary antibacterial abilities against Salmonella and Escherichia coli.

PMID- 22992048
TI  - Liver transplantation--a vision realized.

PMID- 22992047
TI  - The substrate/product-binding modes of a novel GH120 beta-xylosidase (XylC) from
      Thermoanaerobacterium saccharolyticum JW/SL-YS485.
AB  - Xylan-1,4-beta-xylosidase (beta-xylosidase) hydrolyses xylo-oligomers at their
      non-reducing ends into individual xylose units. Recently, XylC, a beta-xylosidase
      from Thermoanaerobacterium saccharolyticum JW/SL-YS485, was found to be
      structurally different from corresponding glycosyl hydrolases in the CAZy
      database (http://www.cazy.org/), and was subsequently classified as the first
      member of a novel family of glycoside hydrolases (GH120). In the present paper,
      we report three crystal structures of XylC in complex with Tris, xylobiose and
      xylose at 1.48-2.05 A (1 A=0.1 nm) resolution. XylC assembles into a tetramer,
      and each monomer comprises two distinct domains. The core domain is a right
      handed parallel beta-helix (residues 1-75 and 201-638) and the flanking region
      (residues 76-200) folds into a beta-sandwich domain. The enzyme contains an open
      carbohydrate-binding cleft, allowing accommodation of longer xylo
      oligosaccharides. On the basis of the crystal structures and in agreement with
      previous kinetic data, we propose that XylC cleaves the glycosidic bond by the
      retaining mechanism using two acidic residues Asp382 (nucleophile) and Glu405
      (general acid/base). In addition to the active site, nine other xylose-binding
      sites were consistently observed in each of the four monomers, providing a
      possible reason for the high tolerance of product inhibition.

PMID- 22992049
TI  - Synthesis of new 4-thiazolidinone-, pyrazoline-, and isatin-based conjugates with
      promising antitumor activity.
AB  - The synthesis and antitumor activity screening of novel 3-[2-(3,5-diaryl-4,5
      dihydropyrazol-1-yl)-4-oxo-4,5-dihydro-1,3-thiazol-5-ylidene]-2,3-dihydro-1H
      indol-2-ones 1-23 and 3-(3,5-diarylpyrazol-1-yl)-2,3-dihydro-1H-indol-2-ones 24
      39 are performed. In vitro anticancer activity of the synthesized compounds was
      tested by the National Cancer Institute. Most of them displayed anticancer
      activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and
      breast cancers cell lines. The structure-activity relationship is discussed. The
      most effective anticancer compound 10 was found to be active with mean GI50 and
      TGI values of 0.071 MUM and 0.76 MUM, respectively. It demonstrated the highest
      antiproliferative influence on the non-small-cell lung cancer cell line HOP-92
      (GI50 < 0.01 MUM), colon cancer line HCT-116 (GI50 = 0.018 MUM), CNS cancer cell
      line SNB-75 (GI50 = 0.0159 MUM), ovarian cancer cell line NCI/ADR-RES (GI50 =
      0.0169 MUM), and renal cancer cell line RXF 393 (GI50 = 0.0197 MUM).

PMID- 22992050
TI  - Physical activity and alcohol use disorders.
AB  - BACKGROUND: Prior research has documented a counterintuitive positive association
      between physical activity and indices of alcohol consumption frequency and
      heaviness. OBJECTIVES: To investigate whether this relation extends to alcohol
      use disorder and clarify whether this association is non-linear. METHODS: This is
      a cross-sectional, correlational population-based study of US adults (N =
      34,653). The Alcohol Use Disorder and Associated Disabilities Interview Schedule
      was used to classify past-year DSM-IV alcohol use disorder and self-reported
      federal government-recommended weekly physical activity cutoffs. RESULTS: After
      statistically controlling for confounds, alcohol abuse but not dependence was
      associated with greater prevalence of physical activity. Number of alcohol use
      disorder symptoms exhibited a curvilinear relationship with meeting physical
      activity requirements, such that the positive association degraded with high
      symptom counts. CONCLUSION: There is a positive association between physical
      activity and less severe forms of alcohol use disorder in US adults. More severe
      forms of alcohol use disorder are not associated with physical activity.

PMID- 22992051
TI  - Biomineralization--an active or passive process?
AB  - Biomineralization is a multifactorial and complex process, which results in the
      deposition of mineral crystals in the extracellular matrix of various tissues.
      Physiological mineralization is restricted to tissues, such as bones, teeth, and
      certain areas of cartilage. Pathological or ectopic mineralization can occur in
      many soft tissues, including articular cartilage, cardiovascular tissues, kidney,
      ligaments, and tendons, and can lead to serious problems. Therefore, the
      understanding of factors and mechanisms that regulate the mineralization process
      is essential for the development of novel therapeutic strategies to prevent or
      inhibit ectopic mineralization. This review will discuss some of the mechanisms
      and factors that regulate physiological mineralization and their potential roles
      in ectopic mineralization. Finally, potential therapeutic approaches for the
      treatment of ectopic mineralization are being discussed.

PMID- 22992052
TI  - "It's a balance between letting it influence life completely and not letting it
      influence life at all"--a qualitative study of migraine prevention from patients'
      perspective.
AB  - PURPOSE: The aim of this study was to elucidate migraine prevention from a
      patient perspective. METHOD: Twenty-one participants who suffered from migraine
      were interviewed and the data analysed by means of qualitative content analysis.
      RESULTS: The analysis revealed two categories; Avoiding migraine triggers and
      introducing migraine inhibiting strategies. In both categories, decisions were
      influenced by an appraisal of the advantages versus disadvantages, attitudes,
      support and knowledge. An overarching theme: "migraine prevention from the
      patients' perspective is a balance between letting it influence life completely
      and not letting it influence life at all" was identified from the interviews.
      CONCLUSIONS: As migraine is a chronic disorder that cannot be cured, merely
      relieved, prevention is of great importance. The present study highlights
      migraine prevention from the patients' perspective and the important issue of how
      much prevention is allowed to influence life. Either of the directions involves a
      risk that life can be controlled by migraine. Acceptance of the disease and
      allowing migraine prevention to influence life to some degree can be a way of
      regaining control. IMPLICATIONS FOR REHABILITATION: * Migraine prevention from
      the patients' perspective is described as a balance between letting it influence
      life completely and not letting it influence life at all, which in either
      direction can lead to a life controlled by migraine. * To take the patients'
      perspectives of the illness in consideration as well as finding the most suitable
      treatment, based on an appraisal of individual advantages versus disadvantages is
      important to meet the need of the patient and to improve migraine prevention.
      Increased knowledge about migraine prevention is imperative both in health care
      and for the individual patient. Support during prevention is requested by
      patients.

PMID- 22992053
TI  - Development of oligonucleotide microarrays onto Si-based surfaces via thioether
      linkage mediated by UV irradiation.
AB  - Selective covalent immobilization of thiolated oligonucleotides onto an epoxy
      functionalized silicon-substrate can be achieved via light radiation (365 nm).
      Following this approach, thiol-modified oligonucleotide probes were covalently
      attached as microarrays, reaching an immobilization density of 2.5 pmol.cm(-2),
      with a yield of 53%. The developed method presents the advantages of spatially
      controlled probe anchoring (by means of using a photomask), direct attachment
      without using cross-linkers, and short irradiation times (10 min). Hybridization
      efficiencies up to 65%, with full complementary strands, were reached. The
      approach was evaluated by scoring single nucleotide polymorphisms with a
      discrimination ratio around 15. Moreover, sensitive and selective detection of
      bacterial  Escherichia coli  was demonstrated.

PMID- 22992054
TI  - Total synthesis of cyclocitropside A and its conversion to cyclocitropsides B and
      C via asparagine deamidation.
AB  - The total syntheses of three closely related cyclic peptide natural products,
      cyclocitropsides A-C, are described. Cyclocitropside A could be readily converted
      into cyclocitropsides B and C through an asparagine deamidation pathway,
      indicating that this is a plausible biosynthetic route to these compounds.

PMID- 22992055
TI  - In situ lyophilisation of nifedipine directly in hard gelatine capsules.
AB  - Hydrophobic drugs present a challenge due to: (i) adhesion and agglomeration;
      hence the choice of the suitable processing technique to have the drugs into
      orally administered dosage forms is critical. (ii) Poor dissolution and poor
      aqueous solubility; hence poor bioavailability. A novel method which is in situ
      lyophilisation directly in hard gelatin capsule shells was used in this research
      to enhance the dissolution of nifedipine (a model hydrophobic drug) in the
      presence of co-povidone, Pluronic((r))F-127 and inulin as enhancement excipients
      (to the best of our knowledge those excipients have not been previously used with
      nifedipine in lyophilised forms). Solutions of nifedipine and excipients in a
      range of concentrations (0.5, 1, 5 and 10%w/v) were prepared using a co-solvent
      system of tert- butyl alcohol/water mixture. These solutions were filled directly
      into bodies of size 000 hard gelatin capsule shells and freeze dried. Pure drug
      and all formulations were characterised by solubility, wetting studies and in
      vitro dissolution. Also, conformational integrity and thermal characteristics of
      nifedipine formulations were investigated using FT-IR spectroscopy and
      differential scanning calorimetry (DSC), respectively. The in situ lyophilisation
      of nifedipine with excipients, looks a promising method not only to improve the
      hydrophobic drug dissolution but also to be cost effective. 

PMID- 22992056
TI  - A reduced linezolid dosage maintains favorable efficacy with minimal hematologic
      toxicity in a methicillin-resistant Staphylococcus aureus-infected patient with
      renal insufficiency.
AB  - The optimal dosage of linezolid to avoid hematologic toxicity is unknown. We
      report the case of an 87-y-old woman with renal insufficiency who developed a
      surgical site infection with refractory methicillin-resistant Staphylococcus
      aureus. The standard dosage of linezolid (1200 mg daily) was not initially
      tolerated by the patient due to severe thrombocytopenia, but she was successfully
      treated when the dose was reduced by half (600 mg daily) based on a population
      pharmacokinetic-pharmacodynamic model. Appropriate dose adjustments can be made
      to optimize linezolid therapy especially in cases with preexisting renal
      dysfunction.

PMID- 22992057
TI  - Spiroligozymes for transesterifications: design and relationship of structure to
      activity.
AB  - Transesterification catalysts based on stereochemically defined, modular,
      functionalized ladder-molecules (named spiroligozymes) were designed, using the
      "inside-out" design strategy, and mutated synthetically to improve catalysis. A
      series of stereochemically and regiochemically diverse bifunctional
      spiroligozymes were first synthesized to identify the best arrangement of a
      pyridine as a general base catalyst and an alcohol nucleophile to accelerate
      attack on vinyl trifluoroacetate as an electrophile. The best bifunctional
      spiroligozyme reacted with vinyl trifluoroacetate to form an acyl-spiroligozyme
      conjugate 2.7 * 10(3)-fold faster than the background reaction with a benzyl
      alcohol. Two trifunctional spiroligozymes were then synthesized that combined a
      urea with the pyridine and alcohol to act as an oxyanion hole and activate the
      bound acyl-spiroligozyme intermediate to enable acyl-transfer to methanol. The
      best trifunctional spiroligozyme carries out multiple turnovers and acts as a
      transesterification catalyst with k(1)/k(uncat) of 2.2 * 10(3) and k(2)/k(uncat)
      of 1.3 * 10(2). Quantum mechanical calculations identified the four transition
      states of the catalytic cycle and provided a detailed view of every stage of the
      transesterification reaction.

PMID- 22992058
TI  - Interpretation of protein adsorption through its intrinsic electric charges: a
      comparative study using a field-effect transistor, surface plasmon resonance, and
      quartz crystal microbalance.
AB  - We describe the highly sensitive detection of the nonspecific adsorption of
      proteins onto a 1-undecanethiol self-assembled monolayer (SAM)-formed gold
      electrode by parallel analysis using field effect transistor (FET), surface
      plasmon resonance (SPR), and quartz crystal microbalance (QCM) sensors. The FET
      sensor detects the innate electric charges of the adsorbed protein at the
      electrode/solution interface, transforming the change in charge density into a
      potentiometric signal in real time, without the requirement for labels. In
      particular, using the Debye-Huckel model, the degree of potential shift was
      proportional to the dry mass of adsorbed albumin and beta-casein. A comparison of
      the FET signal with SPR and QCM data provided information on the conformation and
      orientation of the surface-bound protein by observing characteristic break points
      in the correlation slopes between the signals. These slope transitions reflect a
      multistage process that occurs upon protein adsorption as a function of protein
      concentration, including interim coverage, film dehydration, and monolayer
      condensation. The FET biosensor, in combination with SPR and QCM, represents a
      new technology for interrogating protein-material interactions both
      quantitatively and qualitatively.

PMID- 22992059
TI  - Discovery of novel tubulin inhibitors via structure-based hierarchical virtual
      screening.
AB  - To discover novel tubulin inhibitors, we performed structure-based virtual
      screening against the colchicine binding pocket. In combination with a
      hierarchical docking and scoring procedure, the structural information of an
      additional subpocket in colchicine site was applied to filter out the undesired
      docking hits. This strategy automatically resulted in 63 candidates meeting the
      structural and energetic criteria from a screening library containing
      approximately 100,000 diverse druglike compounds. Among them, nine molecules were
      chosen for experimental validation, which all share the similar binding pose and
      contain an enriched scaffold bearing thiophene core. Encouragingly, five
      compounds are active in tubulin polymerization assay. The most potent inhibitor,
      2-(2-fluorobenzamido)-3-carboxamide-4,5-dimethylthiophene, is structurally
      distinct to any known colchicine site binders and has higher ligand efficiency
      than colchicine. On the basis of its predicted binding pose, we systematically
      probed its binding characteristics by testing series of structural modifications.
      The obtained structure-activity relationship results are consistent with our
      binding model, and the inhibition activities of two analogues are improved by 2
      fold. We expect that the novel structure discovered in the present study may
      serve as a starting point for developing tubulin inhibitors with improved
      efficacy and fewer side effects. We also expect that our hierarchical strategy
      may be generally applicable in structure-based virtual screening campaigns.

PMID- 22992060
TI  - Identification of a novel STAT3 mutation in a patient with hyper-IgE syndrome.
AB  - Here we describe a patient with hyper-IgE syndrome presenting with recurrent
      staphylococcal abscesses, pneumonia, and chronic mucocutaneous candidiasis, and
      report the identification of a novel STAT3 mutation at amino acid position 621,
      which has not previously been described. In addition, we review the
      immunological, infectious, and genetic features of hyper-IgE syndrome.

PMID- 22992062
TI  - Emissions from open burning of simulated military waste from forward operating
      bases.
AB  - Emissions from open burning of simulated military waste from forward operating
      bases (FOBs) were extensively characterized as an initial step in assessing
      potential inhalation exposure of FOB personnel and future disposal alternatives.
      Emissions from two different burning scenarios, so-called "burn piles/pits" and
      an air curtain burner/"burn box", were compared using simulated FOB waste from
      municipal and commercial sources. A comprehensive array of emissions was
      quantified, including CO(2), PM(2.5), volatile organic compounds (VOCs),
      polyaromatic hydrocarbons (PAHs), polychlorinated dibenzodioxins and -furans
      (PCDDs/PCDFs), polybrominated dibenzodioxins and -furans (PBDDs/PBDFs), and
      metals. In general, smoldering conditions in the burn box and the burn pile led
      to similar emissions. However, when the burn box underwent periodic waste
      charging to maintain sustained combustion, PM(2.5), VOCs, and PAH emissions
      dropped considerably compared to smoldering conditions and the overall burn pile
      results. The PCDD/PCDF and PBDD/PBDF emission factors for the burn piles were 50
      times higher than those from the burn box likely due to the dominance of
      smoldering combustion in the burn piles.

PMID- 22992063
TI  - The effectiveness of lumbar drainage in the conservative and surgical treatment
      of traumatic cerebrospinal fluid rhinorrhea.
AB  - CONCLUSIONS: We found no differences in clinicopathologic factors and post
      treatment effects between patients who did and did not receive lumbar drains
      (LDs) in the management of cerebrospinal fluid (CSF) rhinorrhea. Care should be
      taken in using LDs, after considering their effectiveness and complications,
      although routine use of an LD is not indicated in the management of traumatic CSF
      rhinorrhea. OBJECTIVES: We assessed the role and effectiveness of LDs in patients
      managed conservatively and surgically. METHODS: Of 117 patients treated for CSF
      rhinorrhea, 61 were managed conservatively and 56 were initially managed
      surgically. We compared the clinicopathologic features and factors related to
      treatment outcome between patients who did and did not receive LDs. RESULTS: Of
      61 conservatively managed patients, 32 were managed without and 29 with LDs.
      There were no between-group differences in any clinicopathologic factors,
      recurrence rate, or incidence of meningitis during/after treatment, but duration
      of hospitalization differed significantly (15.3 vs 23.2 days, p = 0.03). Of 56
      surgically managed patients, 24 were managed without and 32 with postoperative
      LDs. Except for age, there were no between-group differences in clinicopathologic
      factors. In terms of treatment outcome-related factors, there was no significant
      difference in recurrence rate, incidence of meningitis, or duration of
      hospitalization.

PMID- 22992064
TI  - Dasatinib  for the treatment of Philadelphia chromosome-positive leukemias.
AB  - INTRODUCTION: Dasatinib is a dual Abl/Src tyrosine kinase inhibitor (TKI), which
      was developed to treat patients with chronic myelogenous leukemia (CML), who had
      failed or were intolerant to therapy with imatinib. AREAS COVERED: In this
      article, we review preclinical and clinical studies with dasatinib for the
      therapy of Philadelphia (Ph)-positive leukemias. EXPERT OPINION: Dasatinib is
      very effective in the setting of CML resistance or intolerance to imatinib,
      particularly in patients in chronic phase (CP). Dasatinib is also effective
      against most BCR-ABL1 mutations that arise during therapy with imatinib. Further
      studies have confirmed activity of dasatinib as a single-agent, and combined with
      chemotherapy, for the treatment of patients with Philadelphia-positive acute
      lymphoblastic leukemia (Ph+-ALL). More recently, randomized trials have
      demonstrated that dasatinib is superior to imatinib in the initial therapy of
      patients with CML, and the drug was approved by the FDA for this indication in
      2011.

PMID- 22992066
TI  - Hydrocarbon chain lengthening in catalytic CO hydrogenation: evidence for a CO
      insertion mechanism.
AB  - We studied CO hydrogenation over Co/MgO (10/1) model catalysts using chemical
      transient kinetics. Quantification of the time-dependent response during fast
      changes of the gas flow composition enabled the counting of surface amounts of
      carbon, oxygen, and hydrogen from the onset of adsorption to the steady state of
      the reaction and vice versa. Under the atmospheric pressure conditions of the
      reaction, the total amount of adsorbed species exceeded the monolayer limit on Co
      metal. The time response in transients and back-transients of gaseous reactants
      and products is in accordance with a CO insertion mechanism. Furthermore, the
      Anderson-Schulz-Flory chain lengthening probability is directly proportional to
      the CO pressure, whereas no such dependence is measured for the amounts of
      accumulating or fading surface carbon.

PMID- 22992065
TI  - Tissue-engineered constructs of human oral mucosa examined by Raman spectroscopy.
AB  - A noninvasive quality monitoring of tissue-engineered constructs is a required
      component of any successful tissue-engineering technique. During a 2-week
      production period, ex vivo produced oral mucosa-equivalent constructs (EVPOMEs)
      may encounter adverse culturing conditions that might compromise their quality
      and render them ineffective. We demonstrate the application of near-infrared
      Raman spectroscopy to in vitro monitoring of EVPOMEs during their manufacturing
      process, with the ultimate goal of applying this technology in situ to monitor
      the grafted EVPOMEs. We identify Raman spectroscopic failure indicators for less
      than optimal EVPOMEs that are stressed by higher temperature and exposure to
      higher than normal concentration of calcium ions. Raman spectra of EVPOMEs
      exposed to thermal and calcium stress showed correlation of the band height ratio
      of CH(2) deformation to phenylalanine ring breathing modes, providing a Raman
      metric to distinguish between viable and nonviable constructs. We compared these
      results to histology and glucose consumption measurements, demonstrating that
      Raman spectroscopy is more sensitive and specific to changes in proteins'
      secondary structure not visible by H&E histology. We also exposed the EVPOMEs to
      rapamycin, a cell growth inhibitor and cell proliferation capacity preserver, and
      distinguished between EVPOMEs pretreated with 2 nM rapamycin and controls, using
      the ratio of the Amide III envelope to the phenylalanine band as an indicator.

PMID- 22992067
TI  - Between-school variation in physical activity, aerobic fitness, and organized
      sports participation: a multi-level analysis.
AB  - A large proportion of a child's day is spent at school interacting with certain
      physical surroundings, teachers, and school friends. Thus, schools could have a
      marked impact on establishing physical activity habits. The aim of the present
      study was to assess between-school variation in physical activity, aerobic
      fitness, and organized sports participation. Altogether, we tested 1766 nine- and
      fifteen-year-old children attending 242 school classes at 35 different schools in
      Denmark in 1997-2003. The intra-class correlation coefficient (ICC) for
      objectively assessed physical activity ranged between 0.06 and 0.18 depending on
      the dimension of physical activity and the time considered (i.e. school time vs.
      leisure time). For aerobic fitness, an ICC of 0.10 was observed, whereas that for
      organized sports participation ranged between 0.01 and 0.10 depending on the age
      group. Studying between-school variation in physical activity provides
      information about the extent to which children adjust their physical activity
      habits according to the social and environmental circumstances that they share,
      and helps to plan future school-based physical activity studies, especially in
      terms of sample size and power calculation.

PMID- 22992068
TI  - Interaction of bovine serum albumin with ester-functionalized anionic surface
      active ionic liquids in aqueous solution: a detailed physicochemical and
      conformational study.
AB  - Ester-functionalized anionic surface-active ionic liquids (SAILs), 3-methyl-1
      (ethoxycarbonylmethyl)imidazolium dodecylsulfate
      ([C(1)COOC(2)C(1)im][C(12)SO(4)]) and 3-methyl-1
      (ethoxycarbonylmethyl)pyrrolidinium dodecylsulfate
      ([C(1)COOC(2)C(1)Py][C(12)SO(4)]), were synthesized. The tensiometric profiles
      demonstrate that, in pure water, the studied SAILs exhibit higher surface
      activity than the traditional anionic surfactant, sodium dodecyl sulfate (SDS),
      and cationic SAILs, 1-dodecyl-3-methylimidazolium bromide ([C(12)mim]Br) and N
      dodecyl-N-methylpyrrolidimium bromide (C(12)MPB), with the same hydrocarbon chain
      length. The interaction between bovine serum albumin (BSA) and the anionic SAILs
      in pH 7.4 buffer solution was systematically investigated by various techniques.
      The results show that the cationic ring has a slight effect on the BSA-SAIL
      interaction. The binding isotherms of BSA with the SAILs display four
      characteristic regions with increasing SAIL concentration. The unfolding of BSA
      occurs in the third region. Fluorescence spectroscopy indicates that the studied
      SAILs cause the exposure of tryptophan residues to a hydrophobic environment, and
      [C(1)COOC(2)C(1)im][C(12)SO(4)] can more effectively reduce the fluorescence
      intensity of BSA at low SAIL concentrations than [C(1)COOC(2)C(1)Py][C(12)SO(4)].
      Circular dichroism spectroscopy evidences that the denaturation extent of BSA
      induced by [C(1)COOC(2)C(1)im][C(12)SO(4)] is higher than that of
      [C(1)COOC(2)C(1)Py][C(12)SO(4)].

PMID- 22992070
TI  - Intraoperative aorta balloon occlusion: fertility preservation in patients with
      placenta previa accreta/increta.
AB  - OBJECTIVE: To evaluate whether aorta balloon occlusion decreases the rate of
      hysterectomies and maternal morbidity during extirpative surgery of placenta
      previa accreta or increta. METHODS: We prospectively assessed 33 consecutive
      patients with placenta praevia and MRI diagnosis of multifocal accreta or
      increta. Manual removal of the placenta was performed during a scheduled
      caesarean delivery. In 15 patients, surgery was preceded by balloon
      catheterization of the abdominal aorta (Intra Abdominal Balloon Occlusion: IABO);
      18 patients refusing IABO were considered as controls. We used Fisher's exact
      test for categorical variables and Mann-Whitney test for continuous variables.
      RESULTS: In the IABO group we observed significant decreases in incidence of
      hysterectomy, estimated blood loss, number of transfused units of red blood
      cells, postoperative stay and admission to Intensive Care Unit. No IABO-related
      complications were reported. CONCLUSIONS: During scheduled caesarean section for
      placenta previa multifocally accreta or increta, IABO can prevent hysterectomy in
      many cases and improves perioperative outcome as it gives the operator time to
      achieve the haemostasis via curettage and oversewing of the implantation site
      with acceptable blood loss.

PMID- 22992069
TI  - Assessing the range of kinase autoinhibition mechanisms in the insulin receptor
      family.
AB  - To investigate the range of autoinhibitory mechanisms used by TKDs (tyrosine
      kinase domains) from the insulin receptor family of RTKs (receptor tyrosine
      kinases), we determined crystal structures of TKDs from TrkA (tropomyosin
      receptor kinase A, a nerve growth factor receptor) and Ror2 (receptor tyrosine
      kinase-like orphan receptor 2, an unconventional Wnt receptor). TrkA
      autoinhibition closely resembles that seen for the insulin receptor, relying on
      projection of an activation loop tyrosine residue into the substrate-binding site
      and occlusion of the ATP-binding site by the activation loop. Ror2 employs
      similar mechanisms, but the unusual replacement of the phenylalanine residue in
      its Asp-Phe-Gly motif with leucine necessitates occlusion of the ATP-binding site
      by other means. The unusual Asp-Leu-Gly motif in Ror2 is displaced compared with
      other inactive kinases, allowing the activation loop to interact directly with
      the TKD's alphaC helix, in another mode of autoinhibition that is characteristic
      of the other extreme of this receptor family: ALK (anaplastic lymphoma kinase)
      and Met. These findings provide insight into the expected range of activating
      mutations in these TKDs in cancer. We also describe symmetrical dimers of the
      inactive TrkA TKD resembling those found in other RTKs, possibly reflecting an
      arrangement of kinase domains in a pre-formed TrkA dimer.

PMID- 22992071
TI  - Therapeutic evolution and the challenge of rational medicine.

PMID- 22992074
TI  - Hypoglycemia and risk of death in critically ill patients.
AB  - BACKGROUND: Whether hypoglycemia leads to death in critically ill patients is
      unclear. METHODS: We examined the associations between moderate and severe
      hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per
      liter] and <=40 mg per deciliter [2.2 mmol per liter], respectively) and death
      among 6026 critically ill patients in intensive care units (ICUs). Patients were
      randomly assigned to intensive or conventional glucose control. We used Cox
      regression analysis with adjustment for treatment assignment and for baseline and
      postrandomization covariates. RESULTS: Follow-up data were available for 6026
      patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in
      the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and
      223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the
      intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089
      patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of
      the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe
      hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with
      moderate or severe hypoglycemia, as compared with those without hypoglycemia,
      were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P<0.001) and 2.10 (95% CI,
      1.59 to 2.77; P<0.001), respectively. The association with death was increased
      among patients who had moderate hypoglycemia on more than 1 day (>1 day vs. 1
      day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and
      those who had severe hypoglycemia in the absence of insulin treatment (hazard
      ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001). CONCLUSIONS: In critically ill
      patients, intensive glucose control leads to moderate and severe hypoglycemia,
      both of which are associated with an increased risk of death. The association
      exhibits a dose-response relationship and is strongest for death from
      distributive shock. However, these data cannot prove a causal relationship.
      (Funded by the Australian National Health and Medical Research Council and
      others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).

PMID- 22992076
TI  - Clinical practice. Acute bacterial sinusitis in children.

PMID- 22992077
TI  - Images in clinical medicine. Battle's sign.

PMID- 22992075
TI  - A randomized study of how physicians interpret research funding disclosures.
AB  - BACKGROUND: The effects of clinical-trial funding on the interpretation of trial
      results are poorly understood. We examined how such support affects physicians'
      reactions to trials with a high, medium, or low level of methodologic rigor.
      METHODS: We presented 503 board-certified internists with abstracts that we
      designed describing clinical trials of three hypothetical drugs. The trials had
      high, medium, or low methodologic rigor, and each report included one of three
      support disclosures: funding from a pharmaceutical company, NIH funding, or none.
      For both factors studied (rigor and funding), one of the three possible
      variations was randomly selected for inclusion in the abstracts. Follow-up
      questions assessed the physicians' impressions of the trials' rigor, their
      confidence in the results, and their willingness to prescribe the drugs. RESULTS:
      The 269 respondents (53.5% response rate) perceived the level of study rigor
      accurately. Physicians reported that they would be less willing to prescribe
      drugs tested in low-rigor trials than those tested in medium-rigor trials (odds
      ratio, 0.64; 95% confidence interval [CI], 0.46 to 0.89; P=0.008) and would be
      more willing to prescribe drugs tested in high-rigor trials than those tested in
      medium-rigor trials (odds ratio, 3.07; 95% CI, 2.18 to 4.32; P<0.001). Disclosure
      of industry funding, as compared with no disclosure of funding, led physicians to
      downgrade the rigor of a trial (odds ratio, 0.63; 95% CI, 0.46 to 0.87; P=0.006),
      their confidence in the results (odds ratio, 0.71; 95% CI, 0.51 to 0.98; P=0.04),
      and their willingness to prescribe the hypothetical drugs (odds ratio, 0.68; 95%
      CI, 0.49 to 0.94; P=0.02). Physicians were half as willing to prescribe drugs
      studied in industry-funded trials as they were to prescribe drugs studied in NIH
      funded trials (odds ratio, 0.52; 95% CI, 0.37 to 0.71; P<0.001). These effects
      were consistent across all levels of methodologic rigor. CONCLUSIONS: Physicians
      discriminate among trials of varying degrees of rigor, but industry sponsorship
      negatively influences their perception of methodologic quality and reduces their
      willingness to believe and act on trial findings, independently of the trial's
      quality. These effects may influence the translation of clinical research into
      practice.

PMID- 22992072
TI  - Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple
      sclerosis.
AB  - BACKGROUND: BG-12 (dimethyl fumarate) is in development as an oral treatment for
      relapsing-remitting multiple sclerosis, which is commonly treated with parenteral
      agents (interferon or glatiramer acetate). METHODS: In this phase 3, randomized
      study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg
      two or three times daily, as compared with placebo in patients with relapsing
      remitting multiple sclerosis. An active agent, glatiramer acetate, was also
      included as a reference comparator. The primary end point was the annualized
      relapse rate over a period of 2 years. The study was not designed to test the
      superiority or noninferiority of BG-12 versus glatiramer acetate. RESULTS: At 2
      years, the annualized relapse rate was significantly lower with twice-daily BG-12
      (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with
      placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice
      daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in
      disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer
      acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As
      compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer
      acetate significantly reduced the numbers of new or enlarging T(2)-weighted
      hyperintense lesions (all P<0.001) and new T(1)-weighted hypointense lesions
      (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12
      versus glatiramer acetate, differences were not significant except for the
      annualized relapse rate (thrice-daily BG-12), new or enlarging T(2)-weighted
      hyperintense lesions (both BG-12 doses), and new T(1)-weighted hypointense
      lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events
      occurring at a higher incidence with an active treatment than with placebo
      included flushing and gastrointestinal events (with BG-12) and injection-related
      events (with glatiramer acetate). There were no malignant neoplasms or
      opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG
      12. CONCLUSIONS: In patients with relapsing-remitting multiple sclerosis, BG-12
      (at both doses) and glatiramer acetate significantly reduced relapse rates and
      improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec;
      CONFIRM ClinicalTrials.gov number, NCT00451451.).

PMID- 22992078
TI  - Case records of the Massachusetts General Hospital. Case 29-2012. A 49-year-old
      man with pain and cranial-nerve palsies after treatment of oral cancer.

PMID- 22992079
TI  - The "poison chair" treatment for multiple sclerosis.

PMID- 22992073
TI  - Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.
AB  - BACKGROUND: BG-12 (dimethyl fumarate) was shown to have antiinflammatory and
      cytoprotective properties in preclinical experiments and to result in significant
      reductions in disease activity on magnetic resonance imaging (MRI) in a phase 2,
      placebo-controlled study involving patients with relapsing-remitting multiple
      sclerosis. METHODS: We conducted a randomized, double-blind, placebo-controlled
      phase 3 study involving patients with relapsing-remitting multiple sclerosis.
      Patients were randomly assigned to receive oral BG-12 at a dose of 240 mg twice
      daily, BG-12 at a dose of 240 mg three times daily, or placebo. The primary end
      point was the proportion of patients who had a relapse by 2 years. Other end
      points included the annualized relapse rate, the time to confirmed progression of
      disability, and findings on MRI. RESULTS: The estimated proportion of patients
      who had a relapse was significantly lower in the two BG-12 groups than in the
      placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46%
      with placebo, P<0.001 for both comparisons). The annualized relapse rate at 2
      years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12
      group, as compared with 0.36 in the placebo group, representing relative
      reductions of 53% and 48% with the two BG-12 regimens, respectively (P<0.001 for
      the comparison of each BG-12 regimen with placebo). The estimated proportion of
      patients with confirmed progression of disability was 16% in the twice-daily BG
      12 group, 18% in the thrice-daily BG-12 group, and 27% in the placebo group, with
      significant relative risk reductions of 38% with BG-12 twice daily (P=0.005) and
      34% with BG-12 thrice daily (P=0.01). BG-12 also significantly reduced the number
      of gadolinium-enhancing lesions and of new or enlarging T(2)-weighted
      hyperintense lesions (P<0.001 for the comparison of each BG-12 regimen with
      placebo). Adverse events associated with BG-12 included flushing and
      gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain, as
      well as decreased lymphocyte counts and elevated liver aminotransferase levels.
      CONCLUSIONS: In patients with relapsing-remitting multiple sclerosis, both BG-12
      regimens, as compared with placebo, significantly reduced the proportion of
      patients who had a relapse, the annualized relapse rate, the rate of disability
      progression, and the number of lesions on MRI. (Funded by Biogen Idec; DEFINE
      ClinicalTrials.gov number, NCT00420212.).

PMID- 22992080
TI  - Understanding low sugar from NICE-SUGAR.

PMID- 22992081
TI  - Believe the data.

PMID- 22992082
TI  - Inducing tolerance to pregnancy.

PMID- 22992084
TI  - Eltrombopag in refractory aplastic anemia.

PMID- 22992085
TI  - Eltrombopag in refractory aplastic anemia.

PMID- 22992087
TI  - Cognitive trajectories after postoperative delirium.

PMID- 22992088
TI  - Cognitive trajectories after postoperative delirium.

PMID- 22992090
TI  - Review of novel therapeutics by three regulatory agencies.

PMID- 22992091
TI  - Review of novel therapeutics by three regulatory agencies.

PMID- 22992093
TI  - Exanthematous drug eruptions.

PMID- 22992095
TI  - Progress in immunotherapy of cancer.

PMID- 22992097
TI  - Case 18-2012: A man with neck pain, hoarseness, and dysphagia.

PMID- 22992098
TI  - Case 18-2012: A man with neck pain, hoarseness, and dysphagia.

PMID- 22992099
TI  - Vaccination policies and rates of exemption from immunization, 2005-2011.

PMID- 22992100
TI  - Images in clinical medicine. A tickling in the ear.

PMID- 22992101
TI  - Degradation of a thin Ag layer induced by poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate in a transmission electron
      microscopy specimen of an inverted polymer solar cell.
AB  - It was found that the Ag electrode layer in a transmission electron microscopy
      (TEM) specimen of an inverted polymer solar cell structure of
      Ag/PEDOT:PSS/P3HT:PCBM/TiO(2)/ITO/glass (where PEDOT is poly(3,4
      ethylenedioxythiophene), PSS is polystyrene sulfonate, and ITO is indium tin
      oxide) was broken down into particles as time passed. In order to investigate the
      cause of Ag particle formation and the effect of the degradation on the
      performance of solar cells, the temporal change of the cross-sectional TEM
      micrographs was examined together with energy-dispersive X-ray spectroscopy (EDS)
      analysis and electron tomography. Temporal degradation of Ag/Si and Ag/1 nm
      Ti/PEDOT:PSS/ITO/glass structures was also studied. Absorption of water by the
      PEDOT:PSS layer followed by corrosion of the grain boundaries of the Ag layer by
      the corrosive water was thought to be the reason of Ag particle formation and
      fast performance lowering of the device.

PMID- 22992102
TI  - Blood lead levels in the United States "oldest-old" population.
AB  - CONTEXT: Previous studies have suggested significant endogenous lead release from
      bony stores in the elderly raising the concern for elevated blood lead levels in
      that population. OBJECTIVE: We undertook to determine the range of blood lead
      levels in the "oldest-old" population, a demographic category that includes
      persons aged 80 years and older. MATERIALS AND METHODS: We analyzed blood lead
      level data from the National Health and Nutrition Examination Survey (NHANES) for
      the years 1999-2010 for persons aged 80 years and older. We also screened an
      inner-city population of patients aged 80 years of age and older presenting to an
      emergency department. RESULTS: Among persons aged 80 years and older sampled in
      the NHANES surveys, the geometric mean blood lead level each year varied from
      1.98 to 2.66 mcg/dL. Of the 2,168 measured blood lead levels, only 15 samples
      (0.69%) exceeded our a priori definition of an elevated blood lead level (greater
      than 10 mcg/dL). Of those 15 samples, the highest blood lead level was 15.3
      mcg/dL. For our screening of an inner-city oldest-old population, we enrolled 76
      subjects and found a geometric mean blood lead level of 1.72 mcg/dL. DISCUSSION:
      Several considerations place elderly persons at a theoretically increased risk of
      elevated blood lead level, including previously documented birth cohort effect
      for blood lead levels with older cohorts having higher mean blood lead levels and
      concern for endogenous lead exposure due to release of lead from bony stores.
      However, our statistical analysis of NHANES data and screening of an inner-city
      oldest-old population suggests that elevated blood lead levels in this population
      are rare. CONCLUSION: Routine blood lead level screening in the elderly is not
      indicated.

PMID- 22992103
TI  - Inadvertent intravenous polyethylene glycol 4000 infusion in a child.

PMID- 22992104
TI  - Risk factors related to poor outcome after methanol poisoning and the relation
      between outcome and antidotes--a multicenter study.
AB  - INTRODUCTION. Thorough prognostic and metabolic studies of methanol poisonings
      are scarce. Our aims were to evaluate the factors associated with sequelae and
      death from methanol poisoning, to develop a simple risk-assessment chart to
      evaluate factors associated with sequelae and death from methanol poisoning, and
      to compare the antidotes ethanol and fomepizole. PATIENTS AND METHODS. We present
      a retrospective observational case series of methanol-poisoned patients from
      Norway (1979 and 2002-2005), Estonia (2001) and Tunisia (2003/2004), and patients
      from two different centers in Iran (Teheran 2004-2009 and Mashhad 2009-2010) who
      were identified by a positive serum methanol and had a blood acid-base status
      drawn on admission. The patients were divided into different groups according to
      their outcome: Survived, survived with sequelae, and died. RESULTS. A total of
      320 patients were identified and 117 were excluded. Of the remaining 203
      patients, 48 died, and 34 were discharged with neurological sequelae. A pH < 7.00
      was found to be the strongest risk factor for poor outcome, along with coma
      (Glasgow Coma Scale (GCS) < 8) and a pCO(2) >= 3.1 kPa in spite of a pH < 7.00.
      More patients died despite hyperventilation (low pCO(2)) in the ethanol group.
      CONCLUSIONS. Low pH (pH < 7.00), coma (GCS < 8), and inadequate hyperventilation
      (pCO(2) >= 3.1 kPa in spite of a pH < 7.00) on admission were the strongest
      predictors of poor outcome after methanol poisoning. A simple flow-chart may help
      identify the patients associated with a poor outcome.

PMID- 22992106
TI  - Glycoconjugate vaccines.
AB  - INTRODUCTION: The global disease burden of serious bacterial infections is caused
      mainly by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and
      Neisseria meningitidis. Death or disability may be the potential aftermath of
      invasive infections with these pathogens. Active immunisation is the only
      rational approach in preventing such infections. AREAS COVERED: This review
      discusses the immunology of vaccination and describes the immunogenicity, safety
      and impact of glycoconjugate vaccines that have been developed against Hib, the
      most prevalent serotypes of S. pneumoniae and N. meningitidis serogroups A, C, W
      135 and Y in all ages. The immune response to the plain polysaccharide vaccines
      that target the same pathogens is compared to that induced by the respective
      glycoconjugate vaccine formulations. EXPERT OPINION: Continued surveillance is
      necessary to recognise any epidemiological changes influenced by the impact of
      glycoconjugate vaccines and is crucial in guiding future vaccination strategies.
      Although, in general, the immunogenicity of glycoconjugate vaccines results in
      robust immune responses in all ages, subsequent booster doses may be necessary to
      sustain protection. Challenges in addressing inequities in vaccine availability
      between industrialised and developing countries are still there. The limitations
      of plain polysaccharide vaccines make immunisation with glycoconjugates a more
      sustainable long term option.

PMID- 22992108
TI  - Formation and stabilization of palladium nanoparticles on colloidal graphene
      quantum dots.
AB  - Metal particles supported by carbon materials are important for various
      technologies yet not well understood. Here, we report on the use of well-defined
      colloidal graphene quantum dots as a model system for the carbon materials to
      study metal-carbon interaction. In the case of palladium, our studies show high
      affinity between the metal nanoparticles with the graphene. IR spectroscopy
      reveals covalent nature of the interaction between the two, which had been
      predicted by theoretical calculations yet never directly proven before.

PMID- 22992107
TI  - Modified acidic nonsteroidal anti-inflammatory drugs as dual inhibitors of mPGES
      1 and 5-LOX.
AB  - mPGES-1 is a promising target for development of new anti-inflammatory drugs. We
      aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by
      replacing the carboxylic acid functionality by sulfonamide moieties. Compounds
      were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was
      lonazolac derivative 22 (IC50 = 0.16 MUM), while the best 5-LOX inhibition was
      attained by indomethacin derivative 17 (IC50 = 0.9 MUM). Inhibition of COX-1
      activity was completely removed.

PMID- 22992109
TI  - Short communication: evaluating the level of expressed HIV type 1 gp120 and gag
      proteins in the vCP1521 vector by two immunoplaque methods.
AB  - Over the past few years, several recombinant ALVAC constructs have been used as
      delivery systems in various vaccine research studies and trials. The ALVAC-HIV
      vCP1521 vector has been used as a vaccine delivery system in the RV144 study, a
      phase III HIV study that displayed over 31% protective efficacy. One of the
      important parameters for evaluating the potency of an ALVAC construct is the
      stable expression of proteins encoded by the inserted genes. Herein, the
      expression of inserted gp120 and gag genes in two manufactured ALVAC-HIV vCP1521
      lots have been determined by two immunoplaque methods (dish and plaque lift).
      Both methods were specific and robust and demonstrated that the ALVAC-HIV vCP1521
      lots were able to express gp120 and gag proteins in over 99% of the infectious
      plaques.

PMID- 22992110
TI  - An integrated badnavirus is prevalent in fig germplasm.
AB  - Fig mosaic occurs worldwide and is the most common and important viral disease of
      fig. In the quest to identify the causal agent of the disease, several new
      viruses have been identified, including a new DNA virus, the subject of this
      communication. Phylogenetic analysis placed the virus, provisionally named Fig
      badnavirus-1 (FBV-1), in the genus Badnavirus, family Caulimoviridae. The
      experimental host range of FBV-1 was evaluated and the virus was mechanically
      transmitted to several herbaceous hosts. FBV-1 was detected in the National
      Clonal Germplasm Repository fig collection and additional samples from Arkansas,
      California, Florida, Michigan, Ohio, Oregon, and South Carolina, suggesting its
      wide distribution in the United States. Further tests revealed the presence of
      FBV-1 in seedlings and meristem tissue culture plants. Forty-four isolates were
      used in a study evaluating the population structure of the virus in the United
      States. Evidence that FBV-1 is integrated in the fig genome is presented and
      discussed.

PMID- 22992111
TI  - Incidence and impact of Verticillium dahliae in soil associated with certified
      potato seed lots.
AB  - Verticillium dahliae causes Verticillium wilt of potato and can be found in soil
      associated with potato seed tubers. The purpose of this research was to quantify
      V. dahliae in soil associated with certified seed tubers and determine if this
      potential inoculum source is related to disease development in the field.
      Approximately 68% of seed lots assayed contained V. dahliae-infested soil on seed
      tuber surfaces (seed tuber soil). Over 82% of seed lots contained V. dahliae in
      loose seed lot soil obtained from bags and trucks used to transport seed tubers.
      Most samples contained <=50 CFU/g but some contained >500 CFU/g. Most isolates
      (93%) were vegetative compatibility group 4A. Populations of V. dahliae in stem
      sap increased with increasing inoculum densities in field soils only when V.
      dahliae concentrations in seed tuber soil were low. High concentrations of V.
      dahliae in seed tuber soil resulted in greater stem sap colonization when V.
      dahliae inoculum densities in field soil were low (P < 0.01) and resulted in
      greater pathogen inoculum densities in postharvest field soils (P = 0.04). Seed
      tubers contaminated with V. dahliae-infested soils may introduce the pathogen
      into fields not previously cropped to potato or recontaminate those which have
      received preplant management practices. Long-term management of V. dahliae
      requires reducing propagules in soil associated with seed lots.

PMID- 22992112
TI  - Impact of hydrochloric acid instillation on salvage of infected central venous
      catheters in children with acute lymphoblastic leukaemia.
AB  - BACKGROUND: Bacteraemia associated with indwelling central venous catheters (CVC)
      causes significant morbidity in children with cancer. Hydrochloric acid (HCl)
      instillations have been reported to salvage CVCs with antibiotic-refractory
      infection. We implemented this treatment in 2002. The impact on the survival of
      CVCs has been evaluated in a retrospective cohort study of children with acute
      lymphoblastic leukaemia (ALL). METHODS: Children with newly diagnosed ALL during
      1999-2005 having their first CVC inserted before (n = 16) and after (n = 24) the
      introduction of the procedure were studied. All bacteraemic episodes were
      reviewed, recording bacteriological findings and treatment, and the time to
      premature or planned removal of the CVC was determined. RESULTS: In the
      comparison cohort, 31.0% (9/29) of bacteraemic episodes led to removal of the
      CVC, compared to 5.5% (2/36) in the intervention cohort (p = 0.01). Thus, the
      rate of catheter loss due to infection fell from 56.3% (9/16) to 8.3% (2/24)
      after introducing HCl treatment (p = 0.0025). Overall, the premature catheter
      removal rate fell from 75.0% (12/16) to 45.8% (11/24) (p = 0.10). Analysed in a
      CUSUM plot the reduced frequency of premature CVC removal evidently coincided
      with the introduction of the procedure. In a subgroup analysis of 21
      monobacterial infections with coagulase-negative staphylococci, a decrease in
      systemic and lock antibiotic therapy was found. No adverse events were noted.
      CONCLUSIONS: HCl instillations significantly reduced the need to remove and
      replace CVCs. The procedure is practical, appears to be safe, and may reduce the
      consumption of antibiotics.

PMID- 22992113
TI  - Dynamic adsorption of catechol at the goethite/aqueous solution interface: a
      molecular-scale study.
AB  - Insights from molecular-level mechanisms of catechol adsorption on goethite can
      further our understanding of the fate and transport of hydroxyaromatic compounds
      in the environment. The motivation for our study is to explore the dynamic
      adsorption process of catechol at the goethite/aqueous interface on the molecular
      scale. Multiple complementary techniques including macroscopic adsorption
      experiments, flow-cell ATR-FTIR measurement, 2D IR correlation analysis, and
      quantum chemical calculations were used to study the adsorption mechanisms. Our
      results show that the adsorption of catechol was elevated at high pH but was not
      affected by ionic strength because of the formation of inner-sphere complexes.
      Catechol adsorbed on goethite in mononuclear monodentate and binuclear bidentate
      configurations in the pH range of 5 to 9. Partial mononuclear monodentate
      structures could be converted to binuclear bidentate complexes under basic
      conditions and with increasing surface coverage.

PMID- 22992114
TI  - Low level of antimicrobial resistance in Escherichia coli among Swedish nursing
      home residents.
AB  - BACKGROUND: Screening for bacterial colonization and antimicrobial resistance
      (AMR) among a defined population could aid in the identification of at-risk
      populations and provide targets for antibiotic stewardship and infection control
      programmes. METHODS: Two hundred and sixty-eight participants at 11 Swedish
      nursing homes underwent serial screening for colonization with Escherichia coli
      between March 2008 and September 2010. Seventy-two of the 268 participants (27%)
      were male. The median age was 85 y. Samples were collected from urine, the rectal
      mucosa, the groin, and active skin lesions. RESULTS: Two hundred and nine of 268
      participants (78%) were colonized with E. coli at any body site/fluid. The
      specific colonization rates were 81% (rectum), 48% (urine), 30% (groin), 59%
      (unknown), and 13% (skin lesion). An antibiotic-resistant E. coli isolate was
      identified in 18% of all participants regardless of colonization status; all
      together, 87 resistant isolates were detected. Only 1 participant carried
      isolates with resistance to third-generation cephalosporins (cefotaxime and
      ceftazidime). CONCLUSIONS: The presence of resistance was generally low, and the
      greater part of the resistant cases was connected with 3 common antibiotics:
      ampicillin, trimethoprim/sulfamethoxazole, and ciprofloxacin. In spite of
      generally increasing resistance against third-generation cephalosporins in E.
      coli in Sweden, this study does not implicate residence at a Swedish nursing home
      as a risk factor for the acquisition of expressed cephalosporin resistance.

PMID- 22992115
TI  - Microcystin-LR promotes melanoma cell invasion and enhances matrix
      metalloproteinase-2/-9 expression mediated by NF-kappaB activation.
AB  - This study aimed to explore the molecular mechanisms behind the stimulation
      effects of microcystin-LR (a well-known cyanobacterial toxin produced in
      eutrophic lakes or reservoirs) on cancer cell invasion and matrix
      metalloproteinases (MMPs) expression. Boyden chamber assay showed that
      microcystin-LR exposure (>12.5 nM) evidently enhanced the invasion ability of the
      melanoma cells (MDA-MB-435). Tumor Metastasis PCR Array demonstrated that 24 h
      microcystin-LR treatment (25 nM) caused overexpression of eight genes involved in
      tumor metastasis, including MMP-2, MMP-9, and MMP-13. Quantitative real-time PCR,
      Western blotting and gelatin zymography consistently demonstrated that mRNA and
      protein levels of MMP-2/-9 were increased in the cells after microcystin-LR
      exposure (P < 0.05 each). Immunofluorescence assay and electrophoretic mobility
      shift assay revealed that microcystin-LR could activate nuclear factor kappaB (NF
      kappaB) by accelerating NF-kappaB translocation into the nucleus and enhancing NF
      kappaB binding ability. Furthermore, addition of NF-kappaB inhibitor in culture
      medium could suppress the invasiveness enhancement and MMP-2/-9 overexpression.
      This study indicates that microcystin-LR can act as a NF-kappaB activator to
      promote MMP-2/-9 expression and melanoma cell invasion, which deserves more
      environmental health concerns.

PMID- 22992116
TI  - High efficiency restriction enzyme-free linear amplification-mediated polymerase
      chain reaction approach for tracking lentiviral integration sites does not
      abrogate retrieval bias.
AB  - Retroviral vectors are an efficient and widely employed means of introducing an
      exogenous expression cassette into target cells. These vectors have been shown to
      integrate semi-randomly into the cellular genome, and can be associated with
      genotoxicity due to impact on expression of proximate genes. Therefore, efficient
      and accurate integration site analysis, while quantifying contributions of
      individual vector-containing clones, is desirable. Linear amplification-mediated
      polymerase chain reaction (LAM-PCR) is a widely used technique for identifying
      integrated proviral and host genomic DNA junctions. However, LAM-PCR is subject
      to selection bias inherent in the reliance of the assay on the presence of a
      restriction enzyme-cutting site adjacent to a retrievable integration site, and
      it is further limited by an inability to discriminate prior to sequencing between
      the flanking genomic DNA of interest and uninformative internal vector DNA. We
      report a modified restriction enzyme-free LAM-PCR (Re-free LAM-PCR) approach that
      is less time and labor intensive compared to conventional LAM-PCR, but in
      contrast to some other nonrestrictive methods, compares in efficiency and
      sensitivity, excludes retrieval of uninformative internal vector sequences, and
      allows retrieval of integration sites unbiased by the presence of nearby
      restriction sites. However, we report that Re-free LAM-PCR remains inaccurate for
      quantitation of the relative contributions of individual integration site
      containing clones in a polyclonal setting, suggesting that bias in LAM-PCR
      retrieval of integration sites is not wholly explained by restriction enzyme
      related factors.

PMID- 22992117
TI  - Energy flow in the cryptophyte PE545 antenna is directed by bilin pigment
      conformation.
AB  - Structure-based calculations are combined with quantitative modeling of spectra
      and energy transfer dynamics to detemine the energy transfer scheme of the PE545
      principal light-harvesting antenna of the cryptomonad Rhodomonas CS24. We use a
      recently developed quantum-mechanics/molecular mechanics (QM/MM) method that
      allows us to account for pigment-protein interactions at atomic detail in site
      energies, transition dipole moments, and electronic couplings. In addition,
      conformational flexibility of the pigment-protein complex is accounted for
      through molecular dynamics (MD) simulations. We find that conformational disorder
      largely smoothes the large energetic differences predicted from the crystal
      structure between the pseudosymmetric pairs PEB50/61C-PEB50/61D and PEB82C
      PEB82D. Moreover, we find that, in contrast to chlorophyll-based photosynthetic
      complexes, pigment composition and conformation play a major role in defining the
      energy ladder in the PE545 complex, rather than specific pigment-protein
      interactions. This is explained by the remarkable conformational flexibility of
      the eight bilin pigments in PE545, characterized by a quasi-linear arrangement of
      four pyrrole units. The MD-QM/MM site energies allow us to reproduce the main
      features of the spectra, and minor adjustments of the energies of the three red
      most pigments DBV19A, DBV19B, and PEB82D allow us to model the spectra of PE545
      with a similar quality compared to our original model (model E from Novoderezhkin
      et al. Biophys. J.2010, 99, 344), which was extracted from the spectral and
      kinetic fit. Moreover, the fit of the transient absorption kinetics is even
      better in the new structure-based model. The largest difference between our
      previous and present results is that the MD-QM/MM calculations predict a much
      smaller gap between the PEB50/61C and PEB50/61D sites, in better accord with
      chemical intuition. We conclude that the current adjusted MD-QM/MM energies are
      more reliable in order to explore the spectral properties and energy transfer
      dynamics in the PE545 complex.

PMID- 22992118
TI  - A multiscale computational approach to estimating axonal damage under inertial
      loading of the head.
AB  - A computational modeling framework is developed to estimate the location and
      degree of diffuse axonal injury (DAI) under inertial loading of the head. DAI is
      one of the most common pathological features of traumatic brain injury and is
      characterized by damage to the neural axons in the white matter regions of the
      brain. We incorporate the microstructure of the white matter (i.e., the fiber
      orientations and fiber dispersion) through the use of diffusion tensor imaging
      (DTI), and model the white matter with an anisotropic, hyper-viscoelastic
      constitutive model. The extent of DAI is estimated using an axonal strain injury
      criterion. A novel injury analysis method is developed to quantify the degree of
      axonal damage in the fiber tracts of the brain and identify the tracts that are
      at the greatest risk for functional failure. Our modeling framework is applied to
      analyze DAI in a real-life ice hockey incident that resulted in concussive
      injury. To simulate the impact, two-dimensional finite element (FE) models of the
      head were constructed from detailed MRI and DTI data and validated using
      available human head experimental data. Acceleration loading curves from accident
      reconstruction data were then applied to the FE models. The rotational (rather
      than translational) accelerations were shown to dominate the injury response,
      which is consistent with previous studies. Through this accident reconstruction,
      we demonstrate a conceptual framework to estimate the degree of axonal injury in
      the fiber tracts of the human brain, enabling the future development of
      relationships between computational simulation and neurocognitive impairment.

PMID- 22992119
TI  - Responses of the haploid-to-diploid ratio of isomorphic biphasic life cycles to
      time instability.
AB  - Previous modelling of the haploid-to-diploid ratio (H:D) in biphasic life cycles
      relied on estimates of the stable population growth rate and structure. This is a
      projective analysis that estimates the population dynamics given current
      conditions. However, the environment is rarely constant and has both periodicity
      and random instabilities. The objective of this work was to unveil how the H:D
      responds to them. It was found that ploidy phase dissimilarities on the
      demographic matrix and/or in the initial population structure cause an inevitable
      H:D time variability as a consequence of the life-cycle structure and independent
      of the environmental seasonal cycle. This variability depends on the type of life
      strategy, demographic processes involved and ploidy dissimilar vital rates.
      Furthermore, ploidy dissimilar fertility or growth rates cause cyclic
      oscillations mismatching the seasonal cycle, whereas ploidy dissimilarities in
      the ramet looping rates (survival related) induce a monotonical variation.

PMID- 22992120
TI  - Damaged utricular function clarified by oVEMP in patients with benign paroxysmal
      positional vertigo.
AB  - CONCLUSION: Utricular dysfunction in patients with posterior canal benign
      paroxysmal positional vertigo (pBPPV) was supported by findings for ocular
      vestibular evoked myogenic potential (oVEMP). OBJECTIVE: To evaluate the
      utricular and saccular function in patients with pBPPV. METHODS: This study
      focused on 12 patients definitively diagnosed with pBPPV showing typical
      nystagmus by Dix-Hallpike maneuver and 12 controls. In these subjects, oVEMPs and
      cVEMPs to air-conducted 500 Hz tone burst (125 dB SPL) were measured. The
      patients also underwent caloric tests. RESULTS: More of the patients with pBPPV
      showed abnormal responses in oVEMPs by stimulation on their affected side than
      the controls, while the results of cVEMPs showed no significant differences
      between pBPPV patients and controls. The abnormal results for oVEMPs on the
      affected side showed a higher percentage than those for cVEMPs and caloric tests
      in pBPPV patients. There was no significant association between any of the tests.
      These findings support the possibility that oVEMP reflects the specific abnormal
      condition in pBPPV, i.e. that the urticular function in pBPPV patients was highly
      damaged.

PMID- 22992121
TI  - Vertically oriented iron oxide films produced by hydrothermal process: effect of
      thermal treatment on the physical chemical properties.
AB  - Our study describes the influence of the thermal treatment on the fundamental
      properties of the vertical oriented iron oxide nanorods synthesized under
      hydrothermal condition onto a conductor substrate. X-ray diffraction and X-ray
      absorption near edge structure spectra were used to investigate the phase
      evolution from iron oxyhydroxide (beta-FeOOH) to pure hematite phase. The
      formation of nanorods distributed along of substrate was observed by top-view SEM
      images and the rod growth preferentially oriented at the highly conductive (001)
      basal plane of hematite, perpendicular to the substrate. Light absorption
      capacity increases with the temperature of treatment and the electronic
      transitions (direct and indirect electronic transition) were estimated from this
      result. From the electrochemical measurement, the hematite/electrolyte interface
      was evaluated. These findings demonstrated that the temperature plays an
      important role on the hematite (structural, morphological, and catalytic)
      properties and that many influences must work in great harmony in order to
      produce a promising hematite photoanode.

PMID- 22992123
TI  - Pyrrolo[1,2-a]quinoxalines: novel synthesis via annulation of 2
      alkylquinoxalines.
AB  - In an attempt to synthesize a novel homoleptic complex 3 from 2-methyl-3
      phenylquinoxaline 1 and Ir(acac)(3) for application as a triplet emitter in OLEDs
      (organic light-emitting diodes) no cyclometalation was observed. Instead, an
      annulation to 1-methyl-4-phenylpyrrolo[1,2-a]quinoxaline 2 was observed. Since
      pyrroloquinoxalines are potentially bioactive and few paths for their synthesis
      are known, selected reactions and conditions were investigated, suggesting
      Ir(acac)(3) as catalyst and proving glycerol to be a reactant.

PMID- 22992122
TI  - Functional characterization of the matrix metalloproteinase-1 cigarette smoke
      responsive region and association with the lung health study.
AB  - BACKGROUND: Prior studies have demonstrated that the distal 1.5 kb of the MMP-1
      promoter is fundamental in directing the induction of the MMP-1 gene by cigarette
      smoke. METHODS: To characterize the genetic variants in the MMP-1 cigarette smoke
      responsive element, deep re-sequencing of this element was performed on DNA
      samples from participants in the Lung Health Study. Furthermore, evidence of Sp1
      binding to the MMP-1 promoter was assessed using chromatin immunoprecipitation
      assays and the influence of cigarette smoke exposure on this interaction was
      evaluated in cultured human small airway epithelial cells. RESULTS: Ten
      polymorphisms (four novel) were detected in the cigarette smoke-responsive
      element. Chromatin immunoprecipitation assays to assess the protein-DNA
      interactions at Sp1 sites in the MMP-1 promoter showed increased binding to the
      Sp1 sites in the cigarette smoke-responsive element in small airway epithelial
      cells treated with cigarette smoke extract. In contrast, a Sp1 site outside of
      the element exhibited the opposite effect. None of the polymorphisms were more
      prevalent in the fast decliners versus the slow decliners (fast decliners = mean 
      4.14% decline in FEV1% predicted per year vs. decline in FEV1% predicted per
      year). CONCLUSIONS: Sequencing analyses identified four novel polymorphisms
      within the cigarette smoke-responsive element of the MMP-1 promoter. This study
      identifies functional activity within the cigarette smoke-responsive element that
      is influenced by cigarette smoke and examines this region of the promoter within
      a small patient population.

PMID- 22992124
TI  - Effect of sterically demanding substituents on the conformational stability of
      the collagen triple helix.
AB  - The effect of sterically demanding groups at proline residues on the
      conformational stability of the collagen triple helix was examined. The thermal
      stabilities (T(m) and DeltaG) of eight different triple helices derived from
      collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing
      either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were
      determined and served as a relative measure for the conformational stability of
      the corresponding collagen triple helices. The results show that sterically
      demanding substituents are tolerated in the collagen triple helix when they are
      attached to (4R)-configured amidoprolines in the Xaa position or to (4S)
      configured amidoprolines in the Yaa position. Structural studies in which the
      preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid
      with the Pro and Hyp residues within a crystal structure of collagen revealed
      that the sterically demanding groups point to the outside of these two triple
      helices and thereby do not interfere with the formation of the triple helix. In
      all of the other examined collagen derivatives with lower stability of the triple
      helices, the acetyl or pivaloyl residues point toward the inside of the triple
      helix and clash with a residue of the neighboring strand. The results also
      revealed that unfavorable steric dispositions affect the conformational stability
      of the collagen triple helix more than unfavorable ring puckers of the proline
      residues. The results are useful for the design of functionalized collagen based
      materials.

PMID- 22992125
TI  - Model of elongation of short DNA sequence by thermophilic DNA polymerase under
      isothermal conditions.
AB  - Short DNA sequences, especially those that are repetitive or palindromic, can be
      used as the seeds for synthesis of long DNA by some DNA polymerases in an unusual
      manner. Although several elongation mechanisms have been proposed, there is no
      well-established model that explains highly efficient elongation under isothermal
      conditions. In the present study, we analyzed the elongation of nonrepetitive
      sequences with distinct hairpins at each end. These DNAs were elongated
      efficiently under isothermal conditions by thermophilic Vent (exo(-)) DNA
      polymerase, and the products were longer than 10 kb within 10 min of the
      reaction. A 20-nucleotide DNA with only one hairpin was also elongated. Sequence
      analysis revealed that the long products are mainly tandem repeats of the short
      seed sequences. The thermal melting temperatures of the products were much higher
      than the reaction temperature, indicating that most DNAs form duplexes during the
      reaction. Accordingly, a terminal hairpin formation and self-priming extension
      model was proposed in detail, and the efficient elongation was explained.
      Formation of the hairpin at the 5' end plays an important role during the
      elongation.

PMID- 22992127
TI  - Kinetics of the reversible reaction of CO2(aq) and HCO3(-) with sarcosine salt in
      aqueous solution.
AB  - Aqueous sarcosine salts are fast carbon dioxide (CO(2)) absorbents suitable for
      use in postcombustion CO(2) capture in coal-fired power plants. We have developed
      a detailed reaction scheme including all the reactions in the sarcosine-CO(2)
      water system. All unknown rate and equilibrium constants were obtained by global
      data fitting. We investigated the temperature-dependent rate and equilibrium
      constants of the reaction between aqueous CO(2) and sarcosine using stopped-flow
      spectrophotometry, by following the pH changes over the wavelength range 400-700
      nm via coupling to pH indicators. The corresponding rate and equilibrium
      constants ranged from 15.0 to 45.0  degrees C and were analyzed in terms of
      Arrhenius, Eyring, and van't Hoff relationships. The rate constant for the
      reaction between CO(2) and sarcosine to form the carbamate at 25.0  degrees C is
      18.6(6) * 10(3) M(-1) s(-1), which is very high for an acyclic amine; its
      activation enthalpy is 59(1) kJ mol(-1) and the entropy is 33(4) J mol(-1) K(-1).
      In addition, we investigated the slow reaction between bicarbonate and sarcosine
      using (1)H nuclear magnetic resonance spectroscopy and report the corresponding
      rate and equilibrium constants at 25.0  degrees C. This rate constant is 5.9 *
      10(-3) M(-1) s(-1).

PMID- 22992126
TI  - Anti-Saccharomyces cerevisiae antibodies are elevated in Graves' disease but not
      in Hashimoto's thyroiditis.
AB  - BACKGROUND: Anti-Saccharomyces cerevisiae antibodies (ASCA) had been known to be
      specific for Crohn's disease, but they had also been found in many other
      autoimmune diseases. AIM: The aim of this study was to evaluate the prevalence of
      ASCA in patients with autoimmune thyroid disease (AITD). PATIENTS AND METHODS:
      One hundred and ninety-seven patients with AITD and 160 healthy controls were
      included in the study. One hundred and nineteen patients had Graves' disease (GD)
      and 78 patients had Hashimoto's thyroiditis (HT). ASCA IgG and IgA were
      determined by ELISA. RESULTS: ASCA IgG were significantly more frequent in
      patients with GD than in control group (11.8% vs. 3.1%, p = 0.002). In HT, the
      frequency of ASCA IgG was similar to that of the control group (3.8% and 3.1%
      respectively). The frequency of ASCA IgA was similar in GD (0.8%), HT (2.6%), and
      the control group (3.1%). In all GD patients, the frequency of ASCA IgG was
      significantly higher than that of ASCA IgA (11.8% vs. 0.8%, p = 0.001). These
      results were also true even in male and female groups (10.4% vs. 1.3%, p = 0.01
      and 14.3% vs. 0%, p = 0.01, respectively). ASCA IgG levels were significantly
      higher in GD patients (6.7 +/- 11.1 vs. 2.2 +/- 2.8, p = 3 * 10(-6)) and in HT
      patients (4.2 +/- 4.7 vs. 2.2 +/- 2.8, p = 0.0002) than those in the control
      group. ASCA IgA levels were comparable among patients with GD, HT, and the
      control group. In GD patients, the mean titer of ASCA IgG was significantly
      higher than that of ASCA IgA (6.7 +/- 11.1 vs. 3.6 +/- 4.2, p = 0.005).
      CONCLUSION: Patients with GD had a higher frequency of ASCA IgG than controls.

PMID- 22992128
TI  - Spectrally wide-band terahertz wave modulator based on optically tuned graphene.
AB  - New applications in the realms of terahertz (THz) technology require versatile
      adaptive optics and powerful modulation techniques. Semiconductors have proven to
      provide fast all-optical terahertz wave modulation over a wide frequency band. We
      show that the attenuation and modulation depth in optically driven silicon
      modulators can be significantly enhanced by deposition of graphene on silicon
      (GOS). We observed a wide-band tunability of the THz transmission in a frequency
      range from 0.2 to 2 THz and a maximum modulation depth of 99%. The maximum
      difference between the transmission through silicon and GOS is Deltat = 0.18 at a
      low photodoping power of 40 mW. At higher modulation power, the enhancement
      decreased due to charge carrier saturation. We developed a semianalytical band
      structure model of the graphene-silicon interface to describe the observed
      attenuation and modulation depth in GOS.

PMID- 22992129
TI  - Incidence of viral respiratory pathogens causing exacerbations in adult cystic
      fibrosis patients.
AB  - Respiratory infections caused by respiratory viruses are common in paediatric
      cystic fibrosis (CF) patients and are associated with increased morbidity. There
      is only little data on the incidence of viral respiratory pathogens causing
      exacerbations in the adult CF patient population. In this observational pilot
      study we show, by using molecular as well as conventional techniques for viral
      isolation, that during 1 y a viral pathogen could be isolated in 8/24 (33%) adult
      CF patients who presented with a pulmonary exacerbation. This result shows that
      there is a considerable incidence of viral pathogens in pulmonary exacerbations
      in adult CF patients. Newly identified viruses such as pandemic influenza A/H1N1,
      human metapneumovirus, human bocavirus, and human coronavirus NL63 were not
      detected in our population, except for 1 human coronavirus NL63.

PMID- 22992130
TI  - DFT study of internal alkyne-to-disubstituted vinylidene isomerization in
      [CpRu(PhC=CAr)(dppe)]+.
AB  - Internal alkyne-to-vinylidene isomerization in the Ru complexes ([CpRu(eta(2)
      PhC=CC(6)H(4)R-p)(dppe)](+) (Cp = eta(5)-C(5)H(5); dppe = Ph(2)PCH(2)CH(2)PPh(2);
      R = OMe, Cl, CO(2)Et)) has been investigated using a combination of quantum
      mechanics and molecular mechanics methods (QM/MM), such as ONIOM(B3PW91:UFF), and
      density functional theory (DFT) calculations. Three kinds of model systems (I
      III), each having a different QM region for the ONIOM method, revealed that
      considering both the quantum effect of the substituent of the aryl group in the
      eta(2)-alkyne ligand and that of the phenyl groups in the dppe ligand is
      essential for a correct understanding of this reaction. Several plausible
      mechanisms have been analyzed by using DFT calculations with the B3PW91
      functional. It was found that the isomerization of three complexes (R = OMe,
      CO(2)Et, and Cl) proceeds via a direct 1,2-shift in all cases. The most favorable
      process in energy was path 3, which involves the orientation change of the alkyne
      ligand in the transition state. The activation energies were calculated to be
      13.7, 15.0, and 16.4 kcal/mol, respectively, for the three complexes. Donor
      acceptor analysis demonstrated that the aryl 1,2-shift is a nucleophilic
      reaction. Furthermore, our calculation results indicated that an electron
      donating substituent on the aryl group stabilizes the positive charge on the
      accepting carbon rather than that on the migrating aryl group itself at the
      transition state. Therefore, unlike the general nucleophilic reaction, the less
      electron-donating aryl group has an advantage in the migration.

PMID- 22992131
TI  - Upregulation of CD40/CD40L system in rheumatic mitral stenosis with or without
      atrial fibrillation.
AB  - Platelet activation occurs in peripheral blood of patients with rheumatic mitral
      stenosis (MS) and atrial fibrillation (AF) and could be related to abnormal
      thrombogenesis. The CD40/CD40 ligand (CD40L) which reflects platelet activation,
      mediate a central role in thrombotic diseases. However, the role of CD40/CD40L
      system in rheumatic MS with or without AF remains unclear. Expressions of CD40 on
      monocytes and CD40L on platelets were determined by whole blood flow cytometry
      and serum levels of soluble CD40L were measured by enzyme-linked immunosorbent
      assay in group 1 (19 patients with MS) and group 2 (20 patients with MS and AF)
      compared to group 3 (10 controls). Patients with groups 1 and 2 had a significant
      increase in expression of CD40 on monocytes (P1 and P2 = 0.000) and serum levels
      of sCD40L (P1 = 0.014 and P2 = 0.033, respectively), but nonsignificant increase
      in expression of CD40L on platelets (P1 = 0.109 and P2 = 0.060, respectively) as
      compared to controls. There were no significant difference in all the parameters
      in group 1 compared to group 2. Correlation analysis demonstrated that there was
      a significant direct relationship between the severity of MS and serum levels of
      sCD40L (r = -0.469, p = 0.043). In conclusion, rheumatic MS patients with or
      without AF had upregulation of the CD40/CD40L system as well as elevated sCD40L
      levels. The levels of sCD40L had a significantly direct relationship with the
      severity of MS and it was the stenotic mitral valve, not AF, that had a
      significant impact on platelet activation.

PMID- 22992132
TI  - Effect of surface texturing on superoleophobicity, contact angle hysteresis, and
      "robustness".
AB  - Previously, we reported the creation of a fluorosilane (FOTS) modified pillar
      array silicon surface comprising ~3-MUm-diameter pillars (6 MUm pitch with ~7 MUm
      height) that is both superhydrophobic and superoleophobic, with water and
      hexadecane contact angles exceeding 150 degrees  and sliding angles at ~10
      degrees  owing to the surface fluorination and the re-entrant structure in the
      side wall of the pillar. In this work, the effects of surface texturing (pillar
      size, spacing, and height) on wettability, contact angle hysteresis, and
      "robustness" are investigated. We study the static, advancing, and receding
      contact angles, as well as the sliding angles as a function of the solid area
      fraction. The results reveal that pillar size and pillar spacing have very little
      effect on the static and advancing contact angles, as they are found to be
      insensitive to the solid area fraction from 0.04 to ~0.4 as the pillar diameter
      varies from 1 to 5 MUm and the center-to-center spacing varies from 4.5 to 12
      MUm. On the other hand, sliding angle, receding contact angle, and contact angle
      hysteresis are found to be dependent on the solid area fraction. Specifically,
      receding contact angle decreases and sliding angle and hysteresis increase as the
      solid area fraction increases. This effect can be attributable to the increase in
      pinning as the solid area fraction increases. Surface Evolver modeling shows that
      water wets and pins the pillar surface whereas hexadecane wets the pillar surface
      and then penetrates into the side wall of the pillar with the contact line
      pinning underneath the re-entrant structure. Due to the penetration of the
      hexadecane drop into the pillar structure, the effect on the receding contact
      angle and hysteresis is larger relative to that of water. This interpretation is
      supported by studying a series of FOTS pillar array surfaces with varying
      overhang thickness. With the water drop, the contact line is pinned on the pillar
      surface and very little overhang thickness effect was observed. On the other
      hand, the hexadecane drop is shown to wet the pillar surface and the side wall of
      the overhang. It then pins at the lower edge of the overhang structure. A plot of
      the thickness of the overhang as a function of the static, advancing, and
      receding contact angles and sliding angle of hexadecane reveals that static,
      advancing, and receding contact angles decrease and sliding angle increases as
      the thickness of the overhang increases. A larger overhang effect is observed
      with octane due to its lower surface tension. The robustness of the pillar array
      surface against external pressure induced wetting and abrasion was modeled.
      Surface Evolver simulation (with the hexadecane drop) indicates that wetting
      breakthrough pressure as high as ~70 kPa is achievable with 0.5-MUm-diameter
      pillar array FOTS surfaces. Mechanical modeling shows that bending of the pillars
      is the key failure by abrasion, which can be avoided with a short pillar
      structure. The path to fabricate a superoleophobic surface that can withstand the
      external force equivalent of a gentle cleaning blade (up to ~30 kPa) without
      wetting and abrasion failure is discussed.

PMID- 22992133
TI  - Quantum dot and gold nanoparticle immobilization for biosensing applications
      using multidentate imidazole surface ligands.
AB  - A facile approach for modification of solid substrates with multidentate
      imidazole ligands was developed for immobilization of high densities of quantum
      dots (QDs) that were capped with hydrophilic thiol-based ligands, and for
      immobilization of noble metal nanoparticles. Imidazole polymer was synthesized
      using poly(acrylic acid)  as a backbone, and grafted on amine functionalized
      substrate in a two-step approach. The polymer-modified surface was characterized
      using ellipsometry, water contact angle, and X-ray photoelectron spectroscopy.
      Fluorescence spectroscopy and scanning electron microscopy were used to evaluate
      nanoparticle immobilization. Homogeneous, high density (ca. 5 * 10(11) cm(-2)) QD
      films formed via self-assembly were obtained within 4-6 h. Similarly, the
      imidazole polymer was also shown to be effective for immobilization of gold
      nanoparticles as a uniform film. By making use of the pH-sensitive affinity of
      the imidazole rings to zinc on the surface of QDs, it was possible to achieve
      regeneration of functional ligands suitable for subsequent immobilization of new
      QDs. Immobilized QDs were used as a platform for bioconjugation with
      oligonucleotides and peptides. The transduction of nucleic acid hybridization and
      enzyme activity using QDs as energy donors in interfacial fluorescence resonance
      energy transfer (FRET) indicated that the immobilization strategy preserved the
      functional properties of the QDs. The multidentate imidazole ligands used for QD
      immobilization offer the highest denticity of binding in comparison to the
      currently available approaches without compromise in their optical properties and
      ability to interact with biomolecules in solution.

PMID- 22992134
TI  - Antisense-induced messenger depletion corrects a COL6A2 dominant mutation in
      Ullrich myopathy.
AB  - Collagen VI gene mutations cause Ullrich and Bethlem muscular dystrophies.
      Pathogenic mutations frequently have a dominant negative effect, with defects in
      collagen VI chain secretion and assembly. It is agreed that, conversely, collagen
      VI haploinsufficiency has no pathological consequences. Thus, RNA-targeting
      approaches aimed at preferentially inactivating the mutated COL6 messenger may
      represent a promising therapeutic strategy. By in vitro studies we obtained the
      preferential depletion of the mutated COL6A2 messenger, by targeting a common
      single-nucleotide polymorphism (SNP), cistronic with a dominant COL6A2 mutation.
      We used a 2'-O-methyl phosphorothioate (2'OMePS) antisense oligonucleotide
      covering the SNP within exon 3, which is out of frame. Exon 3 skipping has the
      effect of depleting the mutated transcript via RNA nonsense-mediated decay,
      recovering the correct collagen VI secretion and restoring the ability to form an
      interconnected microfilament network into the extracellular matrix. This novel
      RNA modulation approach to correcting dominant mutations may represent a
      therapeutic strategy potentially applicable to a great variety of mutations and
      diseases.

PMID- 22992135
TI  - Plasma-enhanced chemical vapor deposition of n-heptane and methyl methacrylate
      for potential cell alignment applications.
AB  - Plasma-enhanced chemical vapor deposited polymers (plasma polymers) are promising
      candidates for biomaterials applications. In the present study, plasma deposition
      as a fast and easily scalable method was adapted to deposit coatings from n
      heptane and methyl methacrylate monomers onto glass substrates. Linear patterns
      with line and groove widths between 1.25 and 160 MUm were introduced by degrative
      UV-lithography for cell alignment. Differential interference contrast optical
      microscopy, profilometry and atomic force microscopy revealed that the patterned
      surfaces had a smooth, homogeneous appearance and a pattern height of 8 and 45 nm
      for plasma deposited n-heptane and methyl methacrylate, respectively. UV
      lithography increased the oxygen content on the surface drastically as shown by X
      ray photoelectron spectroscopy. After immersion in simulated body fluid for 21
      days, the pattern was still intact, and the ester groups were also maintained for
      the most part as shown by infrared spectroscopy. To test the coatings' potential
      applicability for biomaterial surfaces in a preliminary experiment, we cultured
      murine preosteoblastic MC3T3-E1 cells on these coatings. Light and electron
      microscopically, a normal spindle-shaped and aligned cell morphology was
      observed. At the mRNA level, cells showed no signs of diminished proliferation or
      elevated expression of apoptosis markers. In conclusion, plasma-enhanced chemical
      vapor deposited polymers can be patterned with a fast and feasible method and
      might be suitable materials to guide cell alignment.

PMID- 22992136
TI  - Years of potential life lost due to HIV infection and associated factors based on
      national HIV surveillance data in Latvia, 1991-2010.
AB  - BACKGROUND: Latvia is still experiencing one of the highest human
      immunodeficiency virus (HIV) mortality rates in the European Union, and HIV is
      the 6(th) leading cause of death among young adults (15-39 y) in the country. The
      aim of the study was to determine the years of potential life lost (YPLL) as an
      indicator of premature mortality and the associated factors among people living
      with HIV (PLH) in Latvia. METHODS: Data from the National Registry of HIV/AIDS
      Cases was used for the time period 1991-2010. Data on 738 deaths were analysed.
      The cut-off age for YPLL calculations was 65 y. Univariable analysis was done
      using Mann-Whitney and Kruskal-Wallis tests. A linear regression model was
      constructed for determining the independent effects of the particular factors on
      the number of YPLL. RESULTS: The total number of YPLL due to HIV in Latvia was
      21,097 (50.4/100,000 general population; 511.1/1000 PLH). Each PLH who died had
      lost 28.8 YPLL on average. The numbers of YPLL reflect the population groups most
      affected by the HIV epidemic (young men, non-ethnic Latvians, living in the
      capital city, and being infected via drug injection). Our regression model
      indicated that among deceased PLH, non-Latvian ethnicity and injecting drug use
      as the mode of HIV transmission were associated with an additional 2.4 (p =
      0.003) and 5.7 (p < 0.001) average YPLL, respectively. CONCLUSIONS: A
      considerable number of years of potential life have been lost in Latvia due to
      HIV. YPLL is significantly associated with ethnicity and mode of HIV
      transmission.

PMID- 22992137
TI  - A self-consistent polarization potential model for describing excess electrons
      interacting with water clusters.
AB  - A new polarization model potential for describing the interaction of an excess
      electron with water clusters is presented. This model, which allows for self
      consistent electron-water and water-water polarization, including dispersion
      interactions between the excess electron and the water monomers, gives electron
      binding energies in excellent agreement with high-level ab initio calculations
      for both surface-bound and cavity-bound states of (H(2)O)(n)(-) clusters. By
      contrast, model potentials that do not allow for a self-consistent treatment of
      electron-water and water-water polarization are less successful at predicting the
      relative stability of surface-bound and cavity-bound excess electron states.

PMID- 22992139
TI  - Characterization of chondrocytes cultured on catechin-loaded alginate-chitosan
      scaffolds.
AB  - Bovine chondrocytes were seeded into scaffolds of a high molecular weight
      chitosan and alginate with a pore size of 50-350 MUm with or without catechin. In
      polymerase chain reaction (PCR), unlike type II, collagen type I was no longer
      expressed at day 14. The DNA content increased until day 8 and began declining,
      indicating cell detachment. The GAG content increased during the first 12 days.
      The percentage of round and collagen type II immunoreactive cells increased over
      the time. Catechin has some protective properties on chondrocytes seeded on the
      alginate-chitosan scaffolds during the first 12 days by means of DNA and
      chondrocyte morphology (p < 0.05).

PMID- 22992138
TI  - Efficient induction of specific cytotoxic T lymphocytes against gastric
      adenocarcinoma by a survivin peptide.
AB  - Survivin has been demonstrated to be an excellent target for immunotherapy in
      several types of cancer, but little is known of the efficacy of survivin with
      gastric adenocarcinoma. In this study, a simple method was performed, and
      relatively high efficacy was shown upon inducing survivin-derived peptide
      specific cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells of
      healthy donors. The induced CTLs exhibited specific lysisagainstHLA-A2 matched
      tumor cells in vitro, and similar results were demonstrated in primary cell
      cultures isolated from patients with gastric adenocarcinoma. Up to 30% of
      randomly selected patients could potentially benefit from immunotherapy targeting
      survivin. These results suggested that this survivin epitope peptide could be a
      promising vaccine candidate for immunotherapy for patients with gastric
      adenocarcinoma.

PMID- 22992140
TI  - Immune modulation in Pompe disease treated with enzyme replacement therapy.

PMID- 22992141
TI  - Perspectives and potential roles for the newly discovered NSP4 in the immune
      system.

PMID- 22992142
TI  - Multiple sclerosis treatment: current best practice.

PMID- 22992143
TI  - Genetics and the impact on treatment protocols in patients with rheumatoid
      arthritis.

PMID- 22992145
TI  - Tocilizumab for the treatment of systemic juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in
      childhood, resulting in short- and long-term disability. It includes a
      heterogeneous group of diseases, of which systemic JIA is often resistant to
      treatment. IL-6 plays a significant role in systemic JIA since it is elevated in
      serum and correlates with disease activity, including joint involvement, acute
      phase reactants and fever. Blocking the IL-6-induced signal could therefore be an
      attractive treatment approach. The use of tocilizumab, a humanized anti-IL-6
      receptor antibody, for the treatment of systemic JIA is described. The purpose
      has been to review the controlled clinical trials evaluating the efficacy and
      safety of tocilizumab for the treatment of systemic JIA. In two Phase III
      randomized, double-blind controlled studies a rapid and high response rate has
      been achieved both regarding systemic features and arthritis activity together
      with a tolerable safety profile in children with systemic JIA refractory to
      conventional treatment.

PMID- 22992146
TI  - Belatacept: a new era of immunosuppression?
AB  - Full T-cell activation in alloimmunity requires the engagement of several
      costimulatory molecules. CTLA-4-Ig and its commercially available fusion
      proteins, belatacept and abatacept, are used to block CD80/86 and promote T-cell
      tolerance. Belatacept, a higher binding affinity molecule, is currently approved
      for clinical use in renal transplantation. The results of two Phase III clinical
      trials showed a similar patient/graft survival, with better renal function at a 3
      year follow-up compared with conventional immunosuppression. There was a higher
      risk of early rejection and post-transplant lymphoproliferative disorder,
      especially with EBV-negative patients receiving kidneys from EBV-positive donors.
      Belatacept-treated groups had a better cardiovascular and metabolic profile. The
      authors review both preclinical and human studies of CTLA-4-Igs.

PMID- 22992147
TI  - Selected sessions on immune tolerance and autoimmune disease.
AB  - Immune Tolerance and Autoimmune Disease   Cambridge, UK, 26-27 April 2012   The
      recent Immune Tolerance and Autoimmune Disease conference was held at Emmanuel
      College Cambridge and organized in collaboration with Anne Cooke (Cambridge
      University, UK). The smoothly run and well-planned program allowed international
      experts, academics and scientists to share and discuss recent developments in the
      understanding of the basic mechanisms of immune tolerance, factors governing
      autoimmunity, mediators of autoimmunity and pathogenesis as well as strategies
      for therapeutic intervention. This report outlines some of the highlights from
      the first day of the conference.

PMID- 22992148
TI  - Novel mutation of the activation-induced cytidine deaminase gene in a Tajik
      family: special review on hyper-immunoglobulin M syndrome.
AB  - The hyper-immunoglobulin M (HIGM) syndrome comprises a group of primary
      immunodeficiency disorders characterized by normal or elevated serum levels of
      IgM and low levels of other immunoglobulin classes. Patients with HIGM usually
      suffer from a variety of recurrent infections. Herein, we report two siblings of
      a Tajik family with a HIGM phenotype in which a novel missense mutation in the
      activation-induced cytidine deaminase (AICDA) gene was detected. Mutations in
      this gene are responsible for an autosomal recessive form of HIGM. We have also
      reviewed and summarized all published cases with HIGM due to defects in AICDA.

PMID- 22992149
TI  - Cross presentation of antigen by dendritic cells: mechanisms and implications for
      immunotherapy.
AB  - Dendritic cells (DCs) possess the specialized potential to present exogenously
      derived antigen to cytotoxic T lymphocytes to elicit an immune response. This
      process, termed cross presentation, is crucial in the generation of immune
      response to viruses, tumors and in autoimmune disease. The ability of DCs to
      cross-present exogenous antigen to cytotoxic T lymphocytes makes them an
      attractive target for exploitation in immunotherapy. In recent years, significant
      advances have been made in understanding the mechanism of cross-presentation and
      the DC subsets involved. The recent discovery of the human cross presenting DC
      has given this field a new lease of life. In this report, the authors provide an
      overview of cross-presentation of antigen by DCs, focusing on the current
      understanding of the molecular mechanisms of the process. The authors also
      discuss the DC subsets involved in cross presentation and its role in health and
      disease.

PMID- 22992150
TI  - Adult and pediatric clinical trials of sublingual immunotherapy in the USA.
AB  - Specific allergen immunotherapy has been practiced for allergic
      rhinoconjunctivitis for over 100 years and is the only treatment option that is
      disease modifying. In the USA, immunotherapy is usually administered via
      subcutaneous injection; this is the only route with a US FDA-approved
      formulation. There is growing interest in developing US-standardized formulations
      for the sublingual route, but up until recently there have been few US trials.
      Most of the experience with sublingual immunotherapy (SLIT) comes from Europe,
      where it is widely used and there is a large body of literature supporting its
      use. The purpose of this review is to summarize recent adult and pediatric
      clinical trials of SLIT in the USA. Most of the trials are for inhalant
      allergies, but there is some early work on SLIT as a novel therapy for food
      allergies.

PMID- 22992151
TI  - Immunomodulating options for liver transplant patients.
AB  - Much has changed since the early years of liver transplantation. Improvements in
      post-transplant survival are largely due to more selective and less toxic
      immunosuppression regimens and advances in operative and perioperative care. This
      has allowed liver transplantation to become an extremely successful treatment
      option for patients with endstage liver disease. Beginning with cyclosporine, a
      cyclic endecapeptide of fungal origin and the first of the calcineurin inhibitors
      to find widespread use, immunosuppressive regimens have evolved to include
      additional calcineurin inhibitors, steroids, mTOR inhibitors, antimetabolites and
      antibodies, mostly targeting T-cell activation. This review will present
      currently available immunosuppressive agents used in the perioperative period of
      liver transplantation, as well as maintenance treatments, tailoring therapeutic
      strategies for specific populations, and advances in immune monitoring and
      tolerance.

PMID- 22992152
TI  - Clinical utility of calprotectin and lactoferrin in patients with inflammatory
      bowel disease: is there something new from the literature?
AB  - The identification of noninvasive biomarkers is still one of the major issue for
      gastroenterologists dealing with inflammatory bowel disease patients, due to the
      chronicity of these conditions and the early onset of symptoms in the majority of
      cases. Research attention has focused mainly on fecal proteins, especially
      calprotectin and lactoferrin, and most of the published data are reassuring about
      their applicability in the diagnosis and monitoring of these patients. However,
      there are still pending questions regarding the reliability of fecal proteins
      especially in the era of mucosal healing and biologics.

PMID- 22992154
TI  - Aprosodic speech with insular hyperintensities and 4R Tau pathology on autopsy.
AB  - We describe a 46-year-old woman who presented with a 2-year history of aprosodic
      speech together with apathy and disinhibition. Brain magnetic resonance imaging
      showed subcortical hyperintensities over both insular regions that later extended
      to both frontal and temporal cortices. The post-mortem exam showed a massive tau
      protein deposition throughout the brain. No mutation in the gene MAPT was
      detected. This case illustrates an atypical clinical-radiological presentation of
      a frontotemporal dementia with an unusual speech and abnormal signal of both
      insulae. Furthermore, it reinforces the crucial role of the insula in the
      development of symptoms in frontotemporal dementia. 

PMID- 22992155
TI  - Reductive dissolution of Tl(I)-jarosite by Shewanella putrefaciens: providing new
      insights into Tl biogeochemistry.
AB  - Thallium (Tl) is emerging as a metal of concern in countries such as China due to
      its release during the natural weathering of Tl-bearing ore deposits and mining
      activities. Despite the high toxicity of Tl, few studies have examined the
      reductive dissolution of Tl mineral phases by microbial populations. In this
      study we examined the dissolution of synthetic Tl(I)-jarosite,
      (H(3)O)(0.29)Tl(0.71)Fe(2.74)(SO(4))(2)(OH)(5.22)(H(2)O)(0.78), by Shewanella
      putrefaciens CN32 using batch experiments under anaerobic circumneutral
      conditions. Fe(II) concentrations were measured over time and showed Fe(II)
      production (4.6 mM) in inoculated samples by 893 h not seen in mineral and dead
      cell controls. Release of aqueous Tl was enhanced in inoculated samples whereby
      maximum concentrations in inoculated and cell-free samples reached 3.2  and 2.1
      mM, respectively, by  termination of the experiment. Complementary batch Tl/S.
      putrefaciens sorption experiments were conducted under experimentally relevant pH
      (5 and 6.3) at a Tl concentration of 35 MUM and did not show significant Tl
      accumulation by either live or dead cells. Therefore, in contrast to many metals
      such as Pb and Cd, S. putrefaciens does not represent a sink for Tl in the
      environment and Tl is readily released from Tl-jarosite during both abiotic and
      biotic dissolution.

PMID- 22992156
TI  - Extensive sex- and/or hormone-dependent expression of rat housekeeping genes.
AB  - AIM: Identify sex- and hormone-independent housekeeping genes in rat liver by
      using a commercially available quantitative reverse transcription-polymerase
      chain reaction array designed to measure the expression of 32 rat housekeeping
      genes. RESULTS: We found that the levels of five of the genes were sexually
      dimorphic, 22 genes were overexpressed, and one was underexpressed in multi
      hormone-deficient hypophysectomized rats of both sexes. Only three genes
      fulfilled the stability criteria determined by geNorm and NormFinder as suitable
      housekeeping genes. Normalizing quantitative reverse transcription-polymerase
      chain reaction data with either of these three genes alone, the geometric means
      of any two of the genes, or even the geometric mean of all the three genes,
      produced similar results. In contrast, application of unproven housekeeping genes
      could lead to erroneous conclusions, having found that insulin-like growth factor
      1 messenger RNA levels could be calculated dramatically either as male or as
      female predominant depending on the choice of housekeeping gene. CONCLUSION: It
      is essential to validate the constancy of housekeeping genes under every
      experimental condition. (This research protocol was approved by the university's
      Institutional Animal Care and Use Committee.).

PMID- 22992157
TI  - The frequency and distance of movements of pigs and semen between commercial and
      non-commercial piggeries in New Zealand.
AB  - AIMS: The study was conducted to identify movement patterns of disease conveyors
      in the New Zealand pig industry. The principal objective of the study was to
      identify data relating to the frequency and distance of movements of pigs and
      semen amongst pig holdings. A secondary objective of the study was to generate
      criteria suitable for categorisation of different pig breeding or raising
      operations. METHODS: Prospective data were collected by a census of all known pig
      holdings in New Zealand using a mailed-out questionnaire. RESULTS: The survey
      yielded 1,477 responses (114 commercial and 1,363 non-commercial pig holdings)
      for descriptive analysis. Seven farm-types were created to describe typical pig
      holdings and were based on pig herd inventory, herd type, and participation in
      the movement of pigs or semen: Commercial genetic supplier, commercial feeder,
      commercial weaner producer, para-commercial genetic supplier, para-commercial
      feeder, para-commercial weaner producer, and non-commercial herd. The farm-type
      with the highest frequency of movements off the piggery was the para-commercial
      genetic suppliers with a median of 5.3 movements off per month. Commercial
      feeders had the second highest off farm movement with a median of 4.6 movements
      per month; these primarily represented movements to an abattoir. The highest
      frequencies of movements on to a piggery were experienced by commercial genetic
      suppliers (3.5 per month) and were due to the delivery of semen or replacement
      gilt/boars. Para-commercial and non-commercial farm-types reported less frequent
      movement activities both onto and off the piggery compared to their commercial
      counterparts. Most movements of pigs and semen occurred over distances of less
      than 100 km. CONCLUSIONS: The study showed that New Zealand has a relatively
      small but widely dispersed commercial pig industry with a large number of non
      commercial pig holdings and there was a substantial geographic overlap between
      these industry sectors. Knowledge of the frequency of movements of pigs and semen
      among different pig farm-types and the distance over which these movements occur
      helps to assess the likely connectivity between piggeries, abattoirs, and sale
      yards. However, the study also highlighted the knowledge deficiencies that result
      in the absence of mandatory livestock identification and tracking schemes.
      CLINICAL RELEVANCE: In an industry with substantially more non-commercial pig
      holdings than commercial pig-holdings, key issues such as biosecurity education,
      ensuring sufficient veterinary involvement in non-commercial sectors, and
      building robust systems to ensure border security will remain critical in the
      effort to keep the pig industry at its current level of high health.

PMID- 22992159
TI  - Shock induced chemistry in liquids studied with ultrafast dynamic ellipsometry
      and visible transient absorption spectroscopy.
AB  - The response to ultrafast laser shock loading of nine liquids was monitored in an
      effort to reveal evidence of chemical changes occurring during the first 350 ps
      following the shock front. In an effort to compare molecular structures
      possessing a variety of common bonding patterns, data were acquired for the
      liquids: cyclohexane, cyclohexene, 1,3-cyclohexadiene, benzene, water,
      acetonitrile, acrylonitrile, tert-butylacetylene, and phenylacetylene. Transient
      absorption spectra were measured in the spectral region from 440 to 780 nm over
      shock stress states from 7 to 20 GPa. Ultrafast dynamic ellipsometry was used to
      measure the shock and particle velocity as well as the shocked refractive index.
      Significant transient absorption attributed to chemical reaction was observed for
      shocked phenylacetylene and acrylonitrile. Evidence of volume decreasing chemical
      reactions was also observed in the ultrafast dynamic ellipsometry data for
      phenylacetylene and acrylonitrile. The liquid 1,3-cyclohexadiene exhibited volume
      decreasing reaction in the ultrafast dynamic ellipsometry data but did not
      exhibit an increase in the transient absorption spectra. There was no evidence of
      chemical reaction in cyclohexane, cyclohexene, benzene, water, acetonitrile, or
      tert-butylacetylene in the first 350 ps, despite the application of shock stress
      that was in many cases well above the reaction threshold observed at microsecond
      time scales.

PMID- 22992158
TI  - Site-selective chemistry and the attachment of peptides to the surface of a
      microelectrode array.
AB  - Peptides have been site-selectively placed on microelectrode arrays with the use
      of both thiol-based conjugate additions and Cu(I)-coupling reactions between
      thiols and aryl halides. The conjugate addition reactions used both acrylate and
      maleimide Michael acceptors. Of the two methods, the Cu(I)-coupling reactions
      proved far superior because of their irreversibility. Surfaces constructed with
      the conjugate addition chemistry were not stable at neutral pHs, especially the
      surface using the maleimide acceptor. Once a peptide was placed onto the array,
      it could be monitored in "real-time" for its interactions with a biological
      receptor.

PMID- 22992160
TI  - The effect of D-cycloserine on subliminal cue exposure in spider fearful
      individuals.
AB  - Research on D-cycloserine (DCS) has demonstrated a significant effect on symptom
      reduction in human studies that utilized conventional exposure-based approaches.
      Recent studies have offered promising results for targeting fears through
      subliminal paradigms. In this double-blind, randomized placebo-controlled study,
      45 spider fearful individuals received DCS or placebo pills prior to completing a
      subliminal cue exposure task to images of spiders. Participants completed self
      report questionnaires and a behavioral approach task to a live caged tarantula.
      After repeated exposure to subliminal spider cues, participants in the DCS group
      reported a greater reduction in disgust than individuals in the placebo group. No
      difference was observed in fear ratings. These findings suggest that DCS augments
      the reduction in disgust in spider fearful subjects after subliminal exposure to
      spider cues.

PMID- 22992161
TI  - Nuclear magnetic resonance spectral assignments of alpha-1,4
      galactosyltransferase LgtC from Neisseria meningitidis: substrate binding and
      multiple conformational states.
AB  - Lipopolysaccharide alpha-1,4-galactosyltransferase C (LgtC) from Neisseria
      meningitidis is responsible for a key step in lipooligosaccharide biosynthesis
      involving the transfer of alpha-galactose from the sugar donor UDP-galactose to a
      terminal acceptor lactose. Crystal structures of the complexes of LgtC with
      Mn(2+) and the sugar donor analogue UDP-2-deoxy-2-fluorogalactose in the absence
      and presence of the sugar acceptor analogue 4'-deoxylactose provided key insights
      into the galactosyl-transfer mechanism. Combined with kinetic analyses, the
      enzymatic mechanism of LgtC appears to involve a "front-side attack" S(N)i-like
      mechanism with a short-lived oxocarbenium-phosphate ion pair intermediate. As a
      prerequisite for investigating the required roles of structural dynamics in this
      catalytic mechanism by nuclear magnetic resonance techniques, the transverse
      relaxation-optimized amide (15)N heteronuclear single-quantum correlation and
      methyl (13)C heteronuclear multiple-quantum correlation spectra of LgtC in its
      apo, substrate analogue, and product complexes were partially assigned. This was
      accomplished using a suite of complementary spectroscopic approaches, combined
      with selective isotopic labeling and mutagenesis of all the isoleucine residues
      in the protein. Only ~70% of the amide signals could be detected, whereas more
      than the expected number of methyl signals were observed, indicating that LgtC
      adopts multiple interconverting conformational states. Chemical shift
      perturbation mapping provided insights into substrate and product binding,
      including the demonstration that the sugar donor analogue (UDP-2FGal) associates
      with LgtC only in the presence of a metal ion (Mg(2+)). These spectral
      assignments provide the foundation for detailed studies of the conformational
      dynamics of LgtC.

PMID- 22992162
TI  - Caring for a child with severe intellectual disability in China: the example of
      Rett syndrome.
AB  - PURPOSE: Rett syndrome is one of several genetic disorders known to cause severe
      intellectual and physical disability, mostly in girls. Girls affected by Rett
      syndrome appear to develop normally in the first 6 months of life, after which
      the usual clinical presentation comprises regression of communication and hand
      skills, the appearance of hand stereotypies and impaired gait. Intellectual
      disability affects more than 1.5% of the population of children in developing
      countries yet we know little about the daily lives and support services available
      for them and their caregivers. METHOD: This qualitative study explored the daily
      experiences of 14 mothers and one grandmother caring for a child with Rett
      syndrome in China via telephone interviews. RESULTS: Participants reported a lack
      of education, rehabilitation and support services available to them. Limited
      access to information reduced families' capacity to adequately meet the needs of
      their child. These gaps were further exacerbated by discrimination and perceived
      stigma from some members of the community. CONCLUSIONS: Additional support
      services and educational programs at the governmental level can improve the
      quality of life of persons with an intellectual disability and their families and
      programs involving community participation in the care of people with
      disabilities may help to address discrimination.

PMID- 22992163
TI  - Bimodal response to aspirin loading in acute ST-elevation myocardial infarction.
AB  - Patients with stable coronary disease who exhibit platelet hypo-responsiveness to
      aspirin (ASA) have worse outcomes. Little data exist regarding platelet response
      to ASA in ST-elevation myocardial infarction (STEMI) patients. Our objective was
      to assess acute platelet response to ASA loading in STEMI patients undergoing
      primary percutaneous coronary intervention (PCI). The study comprised 102
      consecutive patients with STEMI. All patients received a loading dose of 300 mg
      chewable ASA upon admission. Platelet reactivity was assessed immediately prior
      to primary PCI, at a median of 95(63 139) minutes after ASA loading. A bimodal
      response to arachidonic acid (AA) stimulation was observed, such that two
      distinct populations could be discerned: "good responders" had a mean AA-induced
      platelet aggregation of 36 +/- 11% vs. 79 +/- 9% for "poor responders." Despite
      equivalent demographic, clinical, and angiographic characteristics, good
      responders were significantly more likely to demonstrate early ST-segment
      resolution >=70% after primary PCI (80% vs. 48%, p = 0.001), suggestive of better
      myocardial reperfusion. Early inhibition of AA-induced platelet aggregation post
      ASA loading in the setting of STEMI is associated with better tissue reperfusion;
      however, a sizeable proportion of patients do not achieve significant inhibition
      of AA-induced platelet aggregation in response to ASA loading at the time of
      primary PCI. 

PMID- 22992164
TI  - Reinforcement of stereolithographic resins for rapid prototyping with cellulose
      nanocrystals.
AB  - We report on the mechanical properties of optically curable stereolithographic
      resins (SLRs) which were reinforced through the addition of small amounts of
      cellulose nanocrystals (CNCs). The resin/filler mixtures are readily accessible
      via simple mixing processes. A detailed rheological investigation of such
      mixtures and the successful processing of these materials on a commercial SLR
      machine show that at low filler concentrations (below 5%) the processability of
      the materials is barely impacted. The storage modulus, E', increased steadily
      with increasing CNC content in the regimes below and above the glass transition.
      A remarkable modulus enhancement was observed in the rubbery regime, where E'
      increased by 166, 233, and 587% for CNC/SLR nanocomposites with 0.5, 1.0, and
      5.0% w/w CNC, respectively. The modulus increase was less pronounced in the
      glassy state, where E' increased by 21, 32 and 57%, for the same compositions.
      The increase in tensile strength was of similar magnitude. In comparison to
      previously reported CNC and carbon-nanofiller based nanocomposites, the presently
      investigated nanocomposites display a comparably large increase of stiffness and
      strength, which appear to originate from the high level of dispersion and the
      intimate contact of the CNCs with the SLR matrix. Through the fabrication of 3
      dimensional parts, it was shown that the CNC-filled resins can be processed with
      standard equipment in a stereolithographic process that is widely used for rapid
      prototyping and rapid manufacturing.

PMID- 22992165
TI  - Vancomycin-resistant Enterococcus faecium meningitis in adults: case series and
      review of the literature.
AB  - BACKGROUND: Vancomycin-resistant Enterococcus faecium (VR E. faecium) is a rare
      cause of meningitis and is associated with substantial mortality. Limited
      therapeutic options are available for the treatment of VR E. faecium meningitis.
      The optimum therapy has not been established. METHODS: We retrospectively
      identified adult cases of meningitis due to VR E. faecium that occurred at the
      Massachusetts General Hospital from 1999 to 2011 and performed a literature
      search for published adult cases using Medline and Embase. RESULTS: At our
      institution, 4 cases of meningitis due to VR E. faecium were identified. Three
      out of our 4 cases were successfully treated with linezolid in combination with
      rifampicin, or with daptomycin in combination with quinupristin-dalfopristin
      (QD), and 1 out of 4 with linezolid monotherapy. The literature search yielded 18
      cases published to date. Published cases showed bacterial cure with linezolid,
      chloramphenicol or QD (intravenous (IV) and intrathecal (IT)) monotherapy, or
      linezolid in combination with ampicillin, gentamicin, rifampicin or
      chloramphenicol, or daptomycin in combination with gentamicin or QD. CONCLUSIONS:
      Bacterial cure of meningitis due to VR E. faecium can be achieved with various
      antimicrobial drugs used as monotherapy or in combination. IT in addition to IV
      therapy should be considered dependent on the pharmacological properties of the
      drugs. We also reported the successful treatment of a case with a vancomycin
      resistant, linezolid-intermediate isolate with QD and daptomycin. The paucity of
      cases with this clinical syndrome does not allow the identification of an optimal
      treatment regimen.

PMID- 22992166
TI  - Over-ground and robotic-assisted locomotor training in adults with chronic
      stroke: a blinded randomized clinical trial.
AB  - PURPOSE: The purpose was to compare the effectiveness of robotic-assisted body
      weight supported treadmill training using the Lokomat((r)) to over-ground gait
      training (OGT) in adults with chronic stroke. METHODS: Participants were randomly
      assigned to the Lokomat((r)) or OGT interventions. Both protocols included 40
      sessions over 8 weeks. Primary outcome measures were the 10-meter walk test and 6
      minute walk distance. Secondary measures included the Functional Independence
      Measure(TM) locomotion score, Fugl-Meyer Lower Extremity Motor Score (FM-LE),
      Barthel Index, and Stroke Impact Scale. Blinded assessors tested the participants
      at baseline, post-intervention, and 3-month follow-up. RESULTS: Eleven
      Lokomat((r)) and nine OGT participants completed the study. Within group
      differences in the FM-LE score and Barthel Index occurred over time from baseline
      to post-intervention and baseline to 3-month follow-up. No other within group
      differences and no between group differences were observed. CONCLUSIONS: Although
      walking measures did not show significant changes between groups, LE motor
      function and physical functional levels improved over time within both groups.
      The Lokomat((r)) may allow aggressive locomotor training, particularly for the
      lower functioning patients who wish to improve walking ability due to apparent
      eased therapist physical burden, when compared to OGT, although an increased risk
      of skin breakdown is present.

PMID- 22992167
TI  - Construction of GPx active centers on natural protein nanodisk/nanotube: a new
      way to develop artificial nanoenzyme.
AB  - Construction of catalytic centers on natural protein aggregates is a challenging
      topic in biomaterial and biomedicine research. Here we report a novel
      construction of artificial nanoenzyme with glutathione peroxidase (GPx)-like
      function. By engineering the surface of tobacco mosaic virus (TMV) coat protein,
      the main catalytic components of GPx were fabricated on TMV protein monomers.
      Through direct self-assembly of the functionalized viral coat proteins, the multi
      GPx centers were installed on these well-defined nanodisks or nanotubes. With the
      help of muti-selenoenzyme centers, the resulting organized nanoenzyme exhibited
      remarkable GPx activity, even approaching the level of natural GPx. The
      antioxidation study on subcell mitochondrial level demonstrated that virus-based
      nanoenzyme exerted excellent capacity for protecting cell from oxidative damage.
      This strategy represents a new way to develop artificial nanoenzymes.

PMID- 22992168
TI  - A new species of Caryospora (Apicomplexa: Eimeriidae) from the bald eagle,
      Haliaeetus leucocephalus (Accipitriformes: Accipitridae), from Kansas.
AB  - Between March 1989 and February 1994, 4 bald eagles ( Haliaeetus leucocephalus )
      from various localities in Kansas were examined for coccidia. One (25%) of the
      bald eagles was found to be passing an undescribed species of Caryospora in its
      feces. Oocysts of Caryospora hanebrinki n. sp. are ellipsoidal to ovoidal with a
      bilayered wall and measure 48.1 * 42.1 MUm with a shape index of 1.2. A
      micropyle, oocyst residuum, and polar granule were absent. Sporocysts are
      spheroidal, 24.8 MUm wide. Stieda, substieda, and parastieda bodies were absent;
      a spheroidal sporocyst residuum is present; it measures 17.5 MUm and is composed
      of many intact homogenous globules with a few dispersed in a loose spiral around
      the sporocysts. This is the first caryosporan documented from the bald eagle and
      is the largest known Caryospora from raptors.

PMID- 22992169
TI  - Macromolecular and morphological evolution of poly(styrene sulfonate) complexes
      with tetradecyltrimethylammonium bromide.
AB  - Macromolecular characteristics and morphology of water-soluble complexes between
      sodium poly(styrene sulfonate) (PSS) and tetradecyltrimethylammonium bromide have
      been followed as a function of surfactant-to-polymer charge ratio (S/P) to elicit
      possible changes in the complexation mechanism. As revealed by light scattering,
      shorter PSS (30 and 150 repeat units) yield multichain complexes while longer PSS
      (450 and 5000 repeat units) form single-chain species throughout 0 < S/P < 0.9.
      Irrespective of PSS chain length, the complexes exist in solution in a swollen
      coil conformation and undergo a compaction with S/P but never collapse into a
      globule. Even when the free PSS chain is too short to coil (30 repeat units), the
      complexes adopt a coiled conformation due to multichain aggregation.
      Morphological changes (manifested by a hypochromic shift in UV spectra of the
      complexes at S/P < 0.5 and an increase in the local surfactant mobility observed
      at S/P > 0.5 by ESR) strongly suggest a change in the formation mechanism of the
      complexes with a transition near S/P = 0.5.

PMID- 22992170
TI  - Coccidiosis in hihi/stitchbirds (Notiomystis cincta) due to coccidia of the
      Eimeriidae.
AB  - AIM: To describe the pathology of coccidiosis in hihi and to provide preliminary
      data on the taxonomy of the coccidia involved using molecular methods. METHODS:
      In an initial study from 1994 to 1997, gross and histopathological examinations
      were performed on 12 dead juvenile hihi from the National Wildlife Centre (NWC)
      at Mt. Bruce. In a second study during 2008-2010 DNA from sporulated oocysts and
      liver tissue was used for PCR analysis and sequencing. Faecal samples were also
      obtained from infected hihi from the NWC and examined for coccidial oocysts,
      which were then sporulated in the laboratory in 1994-1997 and 2007-2009. In
      addition, a post mortem was performed on a dead adult hihi from the NWC in 2008,
      and 18 archived hihi tissues from 11 individual birds stored at the Institute of
      Veterinary, Animal and Biomedical Sciences (IVABS) were used for DNA extraction.
      RESULTS: Severe gross and histopathological changes in the intestine and
      occasionally in the liver were found in the 12 dead birds examined. The
      morphological characteristics of the sporulated oocysts suggested that two types
      of coccidia were present. PCR analysis and sequencing of extracted DNA supported
      the existence of at least two different coccidia species in hihi. These were
      genetically more closely related to the genus Eimeria than to the morphologically
      similar genus Cystisospora (formerly Isospora) of mammals. In addition, one liver
      tissue sample that was examined post mortem was positive for at least two
      different coccidia species of the family Eimeriidae according to sequencing
      results, and the presence of extraintestinal coccidian stages was confirmed.
      CONCLUSIONS: Preliminary morphological and sequencing results suggest that two
      types of eimeriid coccidia are present and at least one of these commonly has
      extraintestinal stages. CLINICAL RELEVANCE: Coccidiosis in hihi is a serious
      disease capable of causing mortalities in juvenile and adult birds in captive
      situations. Treatment and control of the disease will be difficult as the
      extraintestinal stages of the organism are likely to be refractile to oral
      treatment.

PMID- 22992171
TI  - Methicillin-resistant Staphylococcus aureus epidemic restricted to one health
      district in Finland: a population-based descriptive study in Pirkanmaa, Finland,
      years 2001-2011.
AB  - BACKGROUND: The incidence of methicillin-resistant Staphylococcus aureus (MRSA)
      has been low in the Scandinavian countries, including Finland. METHODS: We report
      a population-based, prospective survey of an exceptionally large ongoing MRSA
      epidemic in a Finnish health district (HD), Pirkanmaa HD, during 2001-2011 caused
      by 1 strain, spa t067 (FIN-16). RESULTS: The first FIN-16 case in the HD was
      identified in 2000. Ten years later, 2447 carriers had been found in 95 different
      institutions. MRSA in carriers was mostly health care-associated (98%). The
      epidemic emerged in long-term care facilities and gradually spread to acute
      hospitals. The majority of carriers were elderly people (median age 78 y). Fifty
      two percent of new carriers had an infection with MRSA at the time of detection.
      CONCLUSIONS: The incidence of MRSA in Pirkanmaa HD is substantially higher than
      the incidence for all of Finland. Temporary projects to control MRSA have not
      proved sufficient to contain this large epidemic.

PMID- 22992172
TI  - Self-assembled InGaAs quantum dot clusters with controlled spatial and spectral
      properties.
AB  - Planar quantum dot clusters (QDCs) consisting of six InGaAs quantum dots (QDs)
      formed around a GaAs nanomound are the most sophisticated self-assembled QDCs
      grown by molecular beam epitaxy thus far. We present the first photoluminescence
      measurements on individual hexa-QDCs with high spatial, spectral, and temporal
      resolution. In the best QDCs, the excitons confined in individual QDs are
      remarkably close in energy, exhibiting only a 10 meV spread. In addition, a
      biexponential decay profile and small variation in decay rates for different QDs
      was observed. The homogeneous energetics and dynamics suggest that the sizes,
      shapes, and composition of the QDs within these clusters are highly uniform.

PMID- 22992173
TI  - Nonequilibrium of organic compounds in sediment-water systems. Consequences for
      risk assessment and remediation measures.
AB  - In many cases, sediment risk assessment, and remediation rely on the assumption
      of equilibrium between chemical concentrations in sediment pore water and
      overlying surface water and thus rely on pore water concentrations only and do
      not additionally include assessment of the overlying water concentration.
      Traditionally, the validity of this assumption was insufficiently documented due
      to a lack of data. Recent studies using passive samplers, however, provided
      sufficient data for the first systematic evaluation of the extent of
      disequilibrium between sediment pore water and overlying surface water. Recent
      bioaccumulation studies reveal uncertainty as to which of these concentrations
      govern bioaccumulation by benthic organisms. Here, we provide the first review of
      studies measuring disequilibrium identifying general patterns and implications
      for the aforementioned areas of application. In most studies on water/sediment
      (dis)equilibrium, sediment pore water and overlying surface water are close to
      equilibrium. For lower molecular weight PAHs, overlying water concentrations
      tended to be relative low, which is tentatively ascribed to biodegradation in the
      water column. Substantial nonequilibrium was observed at some hot-spot locations
      such as in semistagnant harbors. In such cases, efficacy of sediment remediation
      measures to improve overlying water quality can be questioned because differences
      between overlying water concentrations at the hot-spots and those at reference
      locations typically are small. For nonequilibrium situations and some benthic
      taxa, exposure may be determined best by pore water concentrations. Improving our
      understanding in this area may further improve risk assessment of contaminated
      sediments.

PMID- 22992174
TI  - Evidence on the identity of the CXCR2 antagonist AZD-5069.
AB  - Crystalline forms A and D of N-[2-[[(2,3-difluoropheny)methyl]thio]-6-{[(1R,2S)
      2,3-dihydroxy-1-methylpropyl]oxy}-4-pyrimidinyl]-1-azetidinesulfonamide are
      claimed. The compound is a previously disclosed CXCR2 chemokine receptor
      antagonist and is claimed to be useful in the treatment of inflammatory diseases
      such as chronic obstructive pulmonary disease (COPD).

PMID- 22992175
TI  - The influence of lipophilicity in drug discovery and design.
AB  - INTRODUCTION: The role of lipophilicity in drug discovery and design is a
      critical one. Lipophilicity is a key physicochemical property that plays a
      crucial role in determining ADMET (absorption, distribution, metabolism,
      excretion, and toxicity) properties and the overall suitability of drug
      candidates. There is increasing evidence to suggest that control of
      physicochemical properties such as lipophilicity, within a defined optimal range,
      can improve compound quality and the likelihood of therapeutic success. AREAS
      COVERED: This review focuses on understanding lipophilicity, techniques used to
      measure lipophilicity, and summarizes the importance of lipophilicity in drug
      discovery and development, including a discussion of its impact on individual
      ADMET parameters as well as its overall influence on the drug discovery and
      design process, specifically within the past 15 years. EXPERT OPINION: A current
      review of the literature reveals a continued reliance on the synthesis of novel
      structures with increased potency, rather than a focus on maintaining optimal
      physicochemical properties associated with ADMET throughout drug optimization.
      Particular attention to the optimum region of lipophilicity, as well as
      monitoring of lipophilic efficiency indices, may contribute significantly to the
      overall quality of candidate drugs at different stages of discovery.

PMID- 22992176
TI  - Swine hemoglobin as a potential source of artificial oxygen carriers, hemoglobin
      vesicles.
AB  - Hemoglobin-based oxygen carriers (HBOCs) have been developed as a transfusion
      alternative and oxygen therapy. The Hb source is usually outdated donated human
      blood or cow blood obtained from cattle industries because of its abundance. This
      study examined the feasibility of using swine Hb ((S)Hb) for preparation of
      cellular-type HBOCs, hemoglobin-vesicles (HbV). Purification of (S)Hb from fresh
      swine whole blood was conducted with processes including carbonylation ((S)HbO(2)
      --> (S)HbCO), pasteurization (60  degrees C, 15 hours) and tangential flow
      ultrafiltration, with yield of 90%. Actually, differential scanning calorimetric
      analysis showed a denaturation temperature of (S)HbCO at 83  degrees C and
      assures its stability during pasteurization. Concentrated (S)HbCO together with
      pyridoxal 5'-phosphate (PLP) as an allosteric effector was encapsulated in
      phospholipid vesicles to prepare (S)HbV. After decarbonylation ((S)HbCO -->
      (S)HbO(2)), the oxygen affinity (P(50)) of (S)Hb changes mainly by PLP, and the
      influence of Cl(-) was small, in a manner similar to that of human Hb ((H)Hb).
      However, after encapsulation, vesicles of (S)HbV showed much lower oxygen
      affinity (higher P(50)) than (H)HbV did. Autoxidation of (S)HbV was slightly
      faster than (H)HbV. Although some differences are apparent in oxygen affinity and
      autoxidation rates, results clarified that (S)Hb is useful as a starting material
      for HbV production.

PMID- 22992177
TI  - A safety evaluation of dexamethasone-releasing cochlear implants: comparative
      study on the risk of otogenic meningitis after implantation.
AB  - CONCLUSION: Dexamethasone released from a cochlear implant seems not to enhance
      the risk for postoperative infections. OBJECTIVE: Dexamethasone has a positive
      impact on hearing preservation for electric acoustic stimulation (EAS). Due to
      their antiproliferative and immunosuppressive properties, steroids may enhance
      the risk of postoperative infections. A comparative study was performed to
      evaluate the risk of pneumococcal meningitis after implantation of dexamethasone
      eluting cochlear implants. METHODS: Thirty guinea pigs were implanted with non
      eluting (n = 15) or dexamethasone-eluting (n = 15) cochlear implant electrode
      dummies. After 5 weeks, animals were exposed to a virulent strain of
      Streptococcus pneumoniae. The two groups were compared based on the meningitis
      rate. Animals were observed for 5 days for signs of meningitis. Meningitis was
      verified by clinical outcome as well as by pleocytosis and presence of bacteria
      in cerebrospinal fluid. Results were confirmed by histological examination of
      brains and cochleae, clinical findings and culture. RESULTS: There was no
      significant difference in meningitis risk between the two groups. In the group
      with non-eluting implants, 3 of 15 animals developed meningitis, while in the
      group with dexamethasone-eluting implants 4 of 15 showed signs of meningitis. In
      this study dexamethasone-releasing implants did not significantly increase the
      risk of postoperative pneumococcal otogenic meningitis.

PMID- 22992178
TI  - A kinetic analysis of the folding and unfolding of OmpA in urea and guanidinium
      chloride: single and parallel pathways.
AB  - The outer membrane protein OmpA from Escherichia coli can fold into lipid
      vesicles and surfactant micelles from the urea-denatured state. However, a
      complete kinetic description of the folding and unfolding of OmpA, which can
      provide the basis for subsequent protein engineering studies of the protein's
      folding pathway, is lacking. Here we use two different denaturants to probe the
      unfolding mechanism of OmpA in the presence of the surfactant octyl maltoside
      (OM). Unfolding of OmpA in the presence of micelles, achieved with the potent
      denaturant guanidinium chloride (GdmCl), leads to single-phase unfolding. In
      contrast, OmpA unfolds in urea only below OM's critical micelle concentration,
      and this occurs in different phases, which we attribute to the existence of
      states that have bound different amounts of surfactant, from completely "naked"
      to partly covered by surfactant. Multiple parallel refolding phases are
      attributed to different levels of collapse prior to folding. Kinetic results used
      to derive the stability of OmpA in surfactant, using either urea or GdmCl as the
      denaturing agent, give comparable results and indicate a minimalist three-state
      folding scheme involving denatured state D, folding intermediate I, and native
      state N. N and I are stabilized by 15.6 and 2.6 kcal/mol, respectively, relative
      to D. The periplasmic domain of OmpA does not contribute to stability in
      surfactant micelles. However, BBP, a minimalist transmembrane beta-barrel version
      of OmpA with shortened loops, is destabilized by ~10 kcal/mol compared to OmpA,
      highlighting loop contributions to OmpA stability.

PMID- 22992179
TI  - Exploration of the relationship between the Manual Ability Classification System
      and hand-function measures of capacity and performance.
AB  - PURPOSE: To further investigate the construct of Manual Ability Classification
      System (MACS) by evaluating the relationship between children's designated MACS
      levels and their outcomes on two different tests of hand function, measuring
      capacity and performance, respectively. Another aim was to use the International
      Classification of Functioning, Disability and Health-Child and Youth version (ICF
      CY) as a framework to explore the uniqueness of the assessments. METHOD: Ninety
      one children with cerebral palsy in MACS levels I-V, aged 5-17 years (mean 9.8,
      SD 3.0) participated. Data were collected using MACS, ABILHAND-Kids and Box and
      Block Test. RESULTS: A strong association between MACS and ABILHAND-Kids (rs = 
      0.88, p < 0.05) and MACS and Box and Block Test (rs = -0.81, p < 0.05) was
      demonstrated. Children's performance differed significantly between the different
      MACS levels (ABILHAND-Kids F (4:86) = 103.86, p < 0.001, Box and Block Test F
      (4:86) = 59.18, p < 0.001). The content comparison with ICF-CY, as a frame of
      reference, showed that these instruments capture fine hand use in the activity
      and participation component. The linking of the instruments to various ICF-CY
      categories demonstrated conceptual differences between the instruments. MACS had
      the broadest representation of ICF-CY domains. CONCLUSIONS: This study
      strengthens the construct, and thereby the validity, of MACS as a classification
      of children's hand function, expressed by the handling of objects in everyday
      activities in their daily environments. IMPLICATIONS FOR REHABILITATION: * This
      study has strengthened the evidence of Manual Ability Classification System
      (MACS) as being a valid and useful classification of children's hand function. *
      The various MACS levels describe different degrees of hand-function impairment. *
      MACS give a broad description of children's manual ability in a variety of daily
      life domains.

PMID- 22992180
TI  - The dendritic cell niche in chronic obstructive pulmonary disease.
AB  - The pulmonary innate immune system is heavily implicated in the perpetual airway
      inflammation and impaired host defense characterizing Chronic Obstructive
      Pulmonary Disease (COPD). The airways of patients suffering from COPD are
      infiltrated by various immune and inflammatory cells including macrophages,
      neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages,
      neutrophils and T lymphocytes is well characterized, the contribution of
      dendritic cells to COPD pathogenesis is still the subject of emerging research. A
      paper by Botelho and colleagues in the current issue of Respiratory Research
      investigates the importance of dendritic cell recruitment in cigarette-smoke
      induced acute and chronic inflammation in mice. Dendritic cells of the healthy
      lung parenchyma and airways perform an important sentinel function and regulate
      immune homeostasis. During inflammatory responses the function and migration
      pattern of these cells is dramatically altered but the underlying mechanisms are
      incompletely understood. Botelho and colleagues demonstrate here the importance
      of IL-1R1/IL-1alpha related mechanisms including CCL20 production in cigarette
      smoke induced recruitment of dendritic cells and T cell activation in the mouse
      lung.

PMID- 22992181
TI  - Serotypes, antimicrobial susceptibility, and beta-lactam resistance mechanisms of
      clinical Haemophilus influenzae isolates from Bulgaria in a pre-vaccination
      period.
AB  - OBJECTIVE: To determine the serotypes, antimicrobial susceptibility, and beta
      lactam resistance mechanisms of Haemophilus influenzae strains isolated from
      invasive and respiratory tract infections (RTIs) prior to the introduction of
      Haemophilus influenzae type b (Hib) vaccination in Bulgaria. METHODS: A total of
      259 isolates were serotyped by polymerase chain reaction. Susceptibility to
      antibiotics and beta-lactamase production were determined, and DNA sequencing of
      the ftsI gene was performed for ampicillin non-susceptible strains. RESULTS: The
      invasive H. influenzae infections in children were mainly due to serotype b
      (94.5% in meningitis and 88.9% in other invasive cases). Non-typeable strains
      (97.4%) were the most frequently found H. influenzae strains in RTIs both in
      children and adults. Non-susceptibility to ampicillin occurred in 22% of all
      strains. Ceftriaxone and levofloxacin were the most active agents tested.
      Ampicillin resistance occurred in 34.4% of invasive strains, and beta-lactamase
      production was the only mechanism found. Among respiratory tract isolates,
      ampicillin non-susceptible strains (18%) were classified into the following
      groups: beta-lactamase-positive, ampicillin-resistant (BLPAR) strains (7.2%);
      beta-lactamase-negative, ampicillin-non-susceptible (BLNAR) strains (8.2%); and
      beta- lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) strains
      (2.6%). Among 21 BLNAR and BLPACR strains there were 9 different patterns of
      multiple-amino acid substitutions in penicillin-binding protein 3. Of these, most
      isolates (81.0%) belonged to group II, defined by the Asn526Lys substitution.
      CONCLUSIONS: Beta-lactamase production was more common among invasive strains
      than in respiratory isolates. BLNAR and BLPACR H. influenzae were found only
      among respiratory tract isolates.

PMID- 22992182
TI  - Quantum chemical study of the initial step of ozone addition to the double bond
      of ethylene.
AB  - The mechanisms of the initial step in chemical reaction between ozone and
      ethylene were studied by multireference perturbation theory methods (MRMP2,
      CASPT2, NEVPT2, and CIPT2) and density functional theory (OPW91, OPBE, and OTPSS
      functionals). Two possible reaction channels were considered: concerted addition
      through the symmetric transition state (Criegee mechanism) and stepwise addition
      by the biradical mechanism (DeMore mechanism). Predicted structures of
      intermediates and transition states, the energies of elementary steps, and
      activation barriers were reported. For the rate-determining steps of both
      mechanisms, the full geometry optimization of stationary points was performed at
      the CASPT2/cc-pVDZ theory level, and the potential energy surface profiles were
      constructed at the MRMP2/cc-pVTZ, NEVPT2/cc-pVDZ, and CIPT2/cc-pVDZ theory
      levels. The rate constants and their ratio for reaction channels calculated for
      both mechanisms demonstrate that the Criegee mechanism is predominant for this
      reaction. These results are also in agreement with the experimental data and
      previous computational results. The structure of DeMore prereactive complex is
      reported here for the first time at the CCSD(T)/cc-pVTZ and CASPT2/cc-pVDZ
      levels. Relative stability of the complexes and activation energies were refined
      by single-point energy calculations at the CCSD(T)-F12/VTZ-F12 level. The IR
      shifts of ozone bands due to formation of complexes are presented and discussed.

PMID- 22992183
TI  - Femtosecond conical intersection dynamics of tryptophan in proteins and
      validation of slowdown of hydration layer dynamics.
AB  - Water motion probed by intrinsic tryptophan shows the significant slowdown around
      protein surfaces, but it is unknown how the ultrafast internal conversion of two
      nearly degenerate states of Trp ((1)L(a) and (1)L(b)) affects the initial
      hydration in proteins. Here, we used a mini-protein with 10 different tryptophan
      locations one at a time through site-directed mutagenesis and extensively
      characterized the conversion dynamics of the two states. We observed all the
      conversion time scales in 40-80 fs by measurement of their anisotropy dynamics.
      This result is significant and shows no noticeable effect on the initial observed
      hydration dynamics and unambiguously validates the slowdown of hydration layer
      dynamics as shown here again in two mutant proteins.

PMID- 22992184
TI  - Pars plana vitrectomy and silicone oil tamponade as a primary treatment for
      retinal detachment caused by macular holes in highly myopic eyes: a risk-factor
      analysis.
AB  - OBJECTIVES: To determine (i) the efficacy of silicone oil tamponade as a primary
      treatment for a retinal detachment (RD) resulting from a macular hole (MH) (MHRD)
      in highly myopic eyes, and (ii) identify variables associated with successful
      retinal re-attachment. METHODS: We retrospectively reviewed 28 eyes of 26 high
      myopia MHRD patients in one hospital. All eyes had been treated with pars plana
      vitrectomy (PPV) and silicone oil tamponade (PPV/silicone oil tamponade). Binary
      logistic regression was used to determine the factor(s) influencing initial
      anatomical success. RESULTS: The initial anatomical success rate was 75% (21 of
      28 eyes); after silicone oil removal, the anatomical success rate was 96.4% (27
      of 28 eyes). MH diameter was the only variable associated with initial anatomical
      success. CONCLUSION: PPV/silicone oil tamponade is a practical choice for
      treatment of MHRD in high myopia. While RDs occasionally re-occur after silicone
      oil treatment, these events are limited and can be managed with simple measures.
      A large MH is a risk factor for recurrent RD.

PMID- 22992185
TI  - Caffeic acid protects tissue antioxidants and DNA content in methamphetamine
      induced tissue toxicity in Sprague Dawley rats.
AB  - Caffeic acid (CA) (3,4-dihydroxycinnamic acid) is among the major hydroxycinnamic
      acids. Hydroxycinnamic acid is the major subgroup of phenolic compounds.
      Methamphetamine (METH) is a potent addictive psychostimulant. Chronic use and
      acute METH intoxication can cause substantial medical consequences, including
      spleen, kidney, liver and heart. The objective of the present study was to
      evaluate the antioxidant activity of CA to protect against oxidative stress and
      DNA damage to various organs in METH toxicity. Thirty-two male Sprague Dawley
      (SD) rats were divided into four equal groups: group 1 was injected (i.p) with
      saline (1 mL/kg) while groups 2,3 and 4 were injected (i.p) with METH (10 mg/kg)
      twice a day over five days period. Where 100 & 200 mg/kg of CA were injected
      (i.p) into groups 3 and 4, respectively one day before exposure to METH
      injections. Tissue antioxidants and DNA content were evaluated in different
      tissues. METH decreased glutathione (GSH) and glutathione peroxidase (GPx) levels
      while increased malondialdehyde (MDA), catalase (CAT) and protein carbonyl levels
      in brain (hypothalamus), liver, and kidney tissues of rats. METH increased
      hyperdiploidy in these tissues and DNA damage results. Prior treatment of CA to
      animals exposed to METH restores the above parameters to the normal levels and
      preserves the DNA content of these tissues. These results were supported by
      histopathological investigations. In conclusion, METH induced oxidative stress
      and DNA damage and pretreatment of CA before METH injections prevented tissue
      oxidative stress and DNA damage in METH-treated animals.

PMID- 22992186
TI  - Inherently electroactive graphene oxide nanoplatelets as labels for single
      nucleotide polymorphism detection.
AB  - Graphene materials are being widely used in electrochemistry due to their
      versatility and excellent properties as platforms for biosensing. However, no
      records show the use of inherent redox properties of graphene oxide as a label
      for detection. Here for the first time we used graphene oxide nanoplatelets
      (GONPs) as electroactive labels for DNA analysis. The working signal comes from
      the reduction of the oxygen-containing groups present on the surface of GONPs.
      The different ability of the graphene oxide nanoplatelets to conjugate to DNA
      hybrids obtained with complementary, noncomplementary, and one-mismatch sequences
      allows the discrimination of single-nucleotide polymorphism correlated with
      Alzheimer's disease. We believe that our findings are very important to open a
      new route in the use of graphene oxide in electrochemistry.

PMID- 22992187
TI  - Facing the dreaded: does mindfulness facilitate coping with distressing
      experiences? A moderator analysis.
AB  - Increasing evidence shows that mindfulness is positively related to mental
      health; however, the nature of this relationship is not fully understood. The
      current study used structural equation modeling to investigate the hypothesis
      that mindfulness moderates the association between the occurrence of unavoidable
      distressing experiences (UDE) and mental health. Participants from a community
      sample (N = 376) completed the Freiburg Mindfulness Inventory, the Positive and
      Negative Affect Scale, the Brief Symptom Inventory, the Inventory of Approach and
      Avoidance Motivation, and the Incongruence Scale. Results indicated that
      mindfulness moderated the association between unavoidable distressing events and
      psychopathological symptoms/negative affect. Thus, mindfulness may contribute to
      enhance the ability to cope with UDE and thus mitigate the detrimental effects of
      these experiences on mental health.

PMID- 22992188
TI  - The Coping with Attention and Memory Complaints Questionnaire (CAMQ):
      psychometric evaluation of an instrument in suspected chronic solvent-induced
      encephalopathy (CSE).
AB  - Long-term occupational exposure to organic solvents may induce chronic solvent
      induced encephalopathy (CSE), leading to neuropsychological impairments. We
      developed the Coping with Attention and Memory Complaints Questionnaire (CAMQ),
      an instrument for the assessment of coping strategies in patients suspected of
      CSE with neuropsychological complaints. Items for the CAMQ were based on existing
      coping dimensions and constructed by experts. The psychometric properties of the
      CAMQ were evaluated in a sample of 307 workers suspected of CSE. Factor analysis
      revealed four coping subscales: active coping, avoidance, acceptance, and seeking
      social support, all with good internal consistency (alphas .71-.78) and good test
      retest reliability (ICCs .67-.82). The subscales demonstrated moderate
      correlations with related external constructs such as anxiety and depression,
      locus of control, meta-memory, mastery and generic coping styles. In conclusion,
      this study: (1) shows that the newly developed CAMQ is a reliable instrument, and
      (2) provides evidence for its validity in assessing coping with complaints of
      memory and attention in CSE-suspected patients. These results may serve for
      further study on coping with complaints of memory and attention, psychological
      adjustment and well-being in CSE patients.

PMID- 22992190
TI  - Typical toxic components in traditional Chinese medicine.
AB  - INTRODUCTION: Traditional Chinese medicine (TCM) is widely used around the world.
      However, with its wide use has been the identification of a number of
      toxicological issues that have severely restricted its use in clinical treatment.
      The identification of these toxic substances within TCM has become somewhat of a
      hot topic in recent years. AREAS COVERED: This article reviews literature
      published on professional authoritative journals in the last 10 years on the
      toxic constituents and toxicology of TCM, including chemical structures,
      absorption and metabolism. The literature search for this article was based, but
      not limited to, toxic constituents including: alkaloids, glycosides, toxic
      proteins, polypeptide, amino acids, phenols or organic acids, terpenes and
      lactones. The authors discuss the toxic substances referring to their toxicity on
      organs, tissues and systems. EXPERT OPINION: More and more toxic constituents
      from different TCMs have been identified, in addition to information on how they
      act in the body at a molecular level. However, the toxicology of TCMs is very
      complex, and although some progress has been made, a lot work is still needed in
      order to put an end to toxic incidents.

PMID- 22992189
TI  - Evolution, substrate specificity and subfamily classification of glycoside
      hydrolase family 5 (GH5).
AB  - BACKGROUND: The large Glycoside Hydrolase family 5 (GH5) groups together a wide
      range of enzymes acting on beta-linked oligo- and polysaccharides, and
      glycoconjugates from a large spectrum of organisms. The long and complex
      evolution of this family of enzymes and its broad sequence diversity limits
      functional prediction. With the objective of improving the differentiation of
      enzyme specificities in a knowledge-based context, and to obtain new evolutionary
      insights, we present here a new, robust subfamily classification of family GH5.
      RESULTS: About 80% of the current sequences were assigned into 51 subfamilies in
      a global analysis of all publicly available GH5 sequences and associated
      biochemical data. Examination of subfamilies with catalytically-active members
      revealed that one third are monospecific (containing a single enzyme activity),
      although new functions may be discovered with biochemical characterization in the
      future. Furthermore, twenty subfamilies presently have no characterization
      whatsoever and many others have only limited structural and biochemical data.
      Mapping of functional knowledge onto the GH5 phylogenetic tree revealed that the
      sequence space of this historical and industrially important family is far from
      well dispersed, highlighting targets in need of further study. The analysis also
      uncovered a number of GH5 proteins which have lost their catalytic machinery,
      indicating evolution towards novel functions. CONCLUSION: Overall, the subfamily
      division of GH5 provides an actively curated resource for large-scale protein
      sequence annotation for glycogenomics; the subfamily assignments are openly
      accessible via the Carbohydrate-Active Enzyme database at
      http://www.cazy.org/GH5.html.

PMID- 22992191
TI  - Adsorption behavior of hydrophobin proteins on polydimethylsiloxane substrates.
AB  - The design of a bioactive surface with appropriate wettability for effective
      protein immobilization has attracted much attention. Previous experiments showed
      that the adsorption of hydrophobic protein HFBI onto a polydimethylsiloxane
      (PDMS) substrate surface can reverse the inherent hydrophobicity of the surface,
      hence making it suitable for immobilization of a secondary protein. In this
      study, atomistic molecular dynamics simulations have been conducted to elucidate
      the adsorption mechanism of HFBI on the PDMS substrate in an aqueous environment.
      Nine independent simulations starting from three representative initial
      orientations of HFBI toward the solid surface were performed, resulting in
      different adsorption modes. The main secondary structures of the protein in each
      mode are found to be preserved in the entire course of adsorption due to the four
      disulfide bonds. The relative binding free energies of the different adsorption
      modes were calculated, showing that the mode, in which the binding residues of
      HFBI fully come from its hydrophobic patch, is most energetically favored. In
      this favorable binding mode, the hydrophilic region of HFBI is fully exposed to
      water, leading to a high hydrophilicity of the modified PDMS surface, consistent
      with experiments. Furthermore, a set of residues consisting of Leu12, Leu24,
      Leu26, Ile27, Ala66, and Leu68 were found to play an important role in the
      adsorption of HFBI on different hydrophobic substrates, irrespective of the
      structural features of the substrates.

PMID- 22992192
TI  - The sonic hedgehog-GLI1 signaling pathway in brain tumor development.
AB  - INTRODUCTION: The sonic hedgehog (Shh) pathway is a regulatory network involved
      in development and cancer. Proteins like Ptch, SMO, and Gli are central to the
      Shh pathway. Other proteins like HHIP, SUFU, Bmi-1, Cyclin D2, Plakoglobin, PAX6,
      Nkx2.2, and SFRP1 are not so well understood in Shh regulation as Gli-1
      downstream target genes. AREAS COVERED: In this review we try to explain the Shh
      pathway components and their role in development and cancer, mainly of the brain.
      A summary of each of the proteins is presented together with an overview of their
      involvement in cancer. EXPERT OPINION: Genetic alterations of the Shh pathway
      have been detected in cancer stem cells, a subgroup of tumor cells implicated in
      the origin and maintenance of tumors, being responsible for cancer recurrence and
      chemotherapy resistance. Cancer stem cells constitute a novel target for
      biomedical researchers. Specifically, the Shh pathway is being explored as a new
      opportunity for targeted therapies against tumors. Therefore, a better knowledge
      of every of the regulators of the Shh pathway is needed.

PMID- 22992193
TI  - Occurrence of IMP-8, IMP-10, and IMP-13 metallo-beta-lactamases located on class
      1 integrons and other extended-spectrum beta-lactamases in bacterial isolates
      from Tunisian rivers.
AB  - BACKGROUND: Antibiotic-resistant bacteria have been surveyed widely in water
      bodies, but few studies have determined the diversity of antibiotic-resistant
      bacteria in river waters. This study was undertaken to investigate the origin of
      resistance among polluted river bacterial isolates in Tunisia. METHODS: In this
      study 128 isolates resistant to beta-lactam antibiotics were obtained from 2
      polluted rivers in the north of Tunisia. Isolates were identified using Phoenix
      phenotyping criteria. The occurrence of bla(TEM), bla(SHV), bla(CTX-M), bla(CMY),
      bla(VIM), and bla(IMP) was studied by polymerase chain reaction (PCR)
      amplification and sequencing, and the genetic relatedness of the 16 IMP-producing
      Klebsiella pneumoniae isolates was analyzed by comparison of XbaI pulsed-field
      gel electrophoresis (PFGE) profiles. RESULTS: Using Phoenix phenotyping criteria,
      diverse genera of bacteria were identified with different rates of prevalence and
      with different minimum inhibitory concentrations against different antibiotics.
      The occurrence of bla(TEM), bla(SHV), bla(CTXM), bla(CMY), bla(VIM), and bla(IMP)
      genes was confirmed. The DNA sequences upstream and downstream of bla(IMP) genes
      were determined, revealing that all IMP-encoding genes constituted the first
      cassette of class 1 integrons, followed by aacA gene cassettes encoding
      aminoglycoside resistance. Comparison of PFGE profiles showed that only 2 of the
      isolates were clonal, the other 14 displaying unique profiles. The bla(CTX-M)
      gene was the most dominant of the extended-spectrum beta-lactamase (ESBL) genes,
      while the bla(TEM) gene was the second-most dominant. CONCLUSION: The discovery
      of highly diverse ESBL-producing bacteria and metallo-beta-lactamases,
      particularly bla(IMP), in polluted river water raises alarms with regard to the
      potential dissemination of antibiotic-resistant bacteria in communities through
      river environments.

PMID- 22992194
TI  - The relationship between fractal dimension and other-race and inversion effects
      in recognising facial emotions.
AB  - There is currently substantial literature to suggest that facial emotion
      recognition is impaired when other-race or inverted faces are presented. This
      study examined circumplex structures for recognising facial emotions under these
      conditions, directly measured those structures using a fractal dimension, and
      examined the difference between fractal dimensions. Results established that
      emotion ratings for the emotion prototypes used were sufficiently accurate under
      all conditions. Fractal analyses showed that the fractal dimensions of the
      circumplexes were significantly higher for recognition of facial emotions in
      other races than in one's own when the faces were presented upright; the fractal
      dimensions of the circumplexes were also higher for recognition of emotions in
      inverted faces than in upright faces in the own-race condition. The results
      suggest that a lower level of facial emotion recognition is associated with
      higher fractal dimension and that an increase of fractal dimension may be
      characterised by lack of facial familiarity.

PMID- 22992195
TI  - Occupational therapists' perceptions about the clinical utility of the 3D
      interior design software.
AB  - PURPOSE: The 3D interior design software (3DIDS) is a technology, which primarily
      allows users to simulate their homes and visualize any changes prior to
      implementing them. This feasibility study aimed to examine occupational
      therapists' perceptions about the clinical utility of the 3DIDS. A secondary aim
      was to explore the attitudes of occupational therapists towards technology in
      general. METHOD: Three focus groups were conducted with 25 occupational
      therapists working with older people in the UK. The qualitative data were
      analysed using inductive thematic analysis. RESULTS: The three main themes that
      were identified were usage and attitudes of technology, opportunities for
      realistic application of the 3DIDS and related threats and benefits for the
      occupational therapy profession. Occupational therapists had a positive attitude
      towards technology. They suggested that the 3DIDS could be used in discharge
      planning and in rehabilitation. They viewed it as a tool that could enhance their
      status within the health care profession and improve communication, but not as a
      tool that should replace the role of the occupational therapist. CONCLUSIONS:
      This research offers new and important findings about the utilization of the
      3DIDS by occupational therapists and provides information as to where this
      technology should be trialled.

PMID- 22992196
TI  - Highly sensitive detection of proteins based on metal-enhanced fluorescence with
      novel silver nanostructures.
AB  - We present a highly sensitive metal enhanced fluorescence (MEF) method based on a
      novel silver nanostructure fabricated with Cy5-functionalized silver
      nanoparticles (AgNPs) and AgNO(3). The analytical performance has been
      demonstrated by microarray detection of streptavidin (SA) and human IgE. The
      fluorescence intensity can be enhanced substantially with the combined use of
      AgNPs and fluorescence enhanced solution (FES). Aptamers have been used for the
      preparation of Tag-C, which demonstrate IgE detection from 0.5 ng/mL to 16 ng/mL,
      and the limit of detection is determined to be 0.25 ng/mL. SEM images show
      nanogaps exist in the aggregated silver nanoparticles and the nanogaps allow for
      the trap of fluorophores in the nanostructures that emit brighter light upon
      excitation. The silver nanostructures formed by Tags and FES proved to be an
      excellent platform for MEF of fluorophores whose excitation and emission occurred
      between 436 nm and 1000 nm. Finite-difference time-domain (FDTD) simulation has
      been carried out to confirm the enhanced electromagnetic field inside silver
      nanostructures, leading to strong overlap/resonance coupling and eventual
      fluorescence enhancement.

PMID- 22992197
TI  - Comparative diffusivity measurements for alginate-based atomized and inkjet
      bioprinted artificial cells using fluorescence microscopy.
AB  - Radial diffusivity profiles of atomized (MC, d = 1800 +/- 200 um) and inkjet
      printed (MI, d = 40 +/- 5 um) alginate-based artificial cells have been generated
      using 2D Fluorescence Microscopy. The passive outward diffusion of FITC-Dextrans
      from MIs (0.5% LV alginate/15% CaCl2 coated with 0.5% Chitosan) and MCs (1.5% MV
      alginate/1.5% CaCl2) was measured and quantified using a Fickian model. As an
      expected outcome of miniaturization, the ratios of the outer layer diffusivities
      defined as D(MIout)/D(MCout) were 4.25 and 5.07 respectively for the 4 and 70 kDa
      markers, indicative of the enhanced diffusive potential of the miniaturized
      capsules.

PMID- 22992198
TI  - Hydration state of the moss Hylocomium splendens and the lichen Cladina stellaris
      governs uptake and revolatilization of airborne alpha- and gamma
      hexachlorocyclohexane.
AB  - The partitioning of alpha- and gamma-hexachlorocyclohexane between air and the
      moss Hylocomium splendens and the lichen Cladina stellaris were studied under
      laboratory conditions. After cultivation of the sample material to obtain a
      common starting point free from outside influence, the material was divided into
      four different treatment categories with different hydration/desiccation regimes.
      The concentrations of the analytes were 3-5 times higher in the hydrated moss or
      lichen than in the desiccated material. The results are in contrast to how these
      compounds are taken up by pine needles in which there is a continuous
      accumulation, more rapid during periods with high temperatures and dry weather.
      In general, the different adaptations to water economy is a more important
      explanatory factor for the concentration of airborne hydrophobic pollutants in
      mosses, lichens, and vascular plants than their designation as "plants" in a
      broad sense. It is, therefore, not advisible to mix data from different organism
      groups for monitoring or modeling purposes.

PMID- 22992199
TI  - Comparison of ( 18 ) F-FLT PET and ( 18 ) F-FDG PET for detection of cervical
      lymph node metastases in head and neck cancers.
AB  - CONCLUSION: Despite low uptake of tracer, 3'-deoxy-3'-(18)F-fluorothymidine (FLT)
      PET could detect cervical lymph node metastases as well as 2-deoxy-2-(18)F-fluoro
      d-glucose (FDG) PET. OBJECTIVE: The diagnostic efficacy of FLT PET was compared
      with that of FDG PET regarding nodal staging of head and neck squamous cell
      cancers. METHODS: Twenty-three patients were examined with FLT PET and FDG PET.
      PET images were evaluated qualitatively for regions of focally increased
      metabolism and maximum standardized uptake values (SUV) were calculated for
      semiquantitative analysis. RESULTS: The mean (+/- SD) FLT SUV in visualized
      metastatic lymph nodes was 4.8 +/- 2.9 as compared with 6.9 +/- 4.9 for FDG SUV
      (p < 0.001). Significant correlations were found between the area of metastatic
      lymph nodes and both FLT SUV (r = 0.8; p < 0.0001) and FDG SUV (r = 0.84; p <
      0.0001). The false-positive (over-staged) and false-negative (under-staged) rates
      for lymph node staging by FLT PET were 4% (1/23) and 17% (4/23), respectively.
      Those for FDG PET were 9% (2/23) and 13% (3/23). All metastatic lymph nodes
      measuring more than 9 mm in short-axis diameter were correctly detected by FLT
      PET. However, both FLT and FDG PET had low sensitivity for detecting the lymph
      node metastases <= 9 mm in short-axis diameter and tumor deposits < 5 mm.

PMID- 22992201
TI  - Effects of long-distance walking on socket-limb interface pressure, tactile
      sensitivity and subjective perceptions of trans-tibial amputees.
AB  - PURPOSE: Many trans-tibial amputees could not tolerate long-distance walking.
      Lack of walking could explain for the increased cardiovascular diseases mortality
      rate. This study investigated the effects of long-distance walking (LDW) on
      socket-limb interface pressure, tactile sensitivity of the residual limb, and
      subjective feedbacks, which potentially identified the difficulties in LDW.
      METHOD: Five male unilateral trans-tibial amputees walked on a level treadmill
      for a total of one hour at comfortable speed. Tactile sensitivity of the residual
      limb and socket-limb interface pressure during over-ground walking were measured
      before and after the treadmill walking. Modified Prosthesis Evaluation
      Questionnaires were also administered. RESULTS: After the treadmill walking, the
      socket-limb interface pressure and the tactile sensitivity at the popliteal
      depression area were significantly reduced. This corresponds well with the
      questionnaire results showing that the level of discomfort and pain of the
      residual limb did not increase. The questionnaire revealed that there were
      significant increases in fatigue level at the sound-side plantar flexors, which
      could lead to impaired dynamic stability. CONCLUSIONS: Fatigue of sound-side
      plantar-flexor was the main difficulty faced by the five subjects when walking
      long-distances. This finding might imply the importance of refining prosthetic
      components and rehabilitation protocols in reducing the muscle fatigue.
      IMPLICATIONS FOR REHABILITATION: * After long-distance walking (LDW) of the trans
      tibal amputee subjects, there were significant increases in fatigue level at the
      plantar flexors. These might explain the reduced walking stability as perceived
      by the subjects. * LDW did not produce any problems in residual-limb comfort and
      pain feeling. These were in line with the significant reductions of socket-limb
      interface pressure and the tactile sensitivity at the popliteal depression after
      LDW. * Refinements of prosthetic components and rehabilitation protocols should
      be attempted to reduce the fatigue of the plantar flexors and facilitate LDW.

PMID- 22992200
TI  - Cigarette smoke-induced accumulation of lung dendritic cells is interleukin
      1alpha-dependent in mice.
AB  - BACKGROUND: Evidence suggests that dendritic cells accumulate in the lungs of
      COPD patients and correlate with disease severity. We investigated the importance
      of IL-1R1 and its ligands IL-1alpha and beta to dendritic cell accumulation and
      maturation in response to cigarette smoke exposure. METHODS: Mice were exposed to
      cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL
      1alpha-deficient mice, as well as anti-IL-1alpha and anti-IL-1beta blocking
      antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell
      accumulation and activation. RESULTS: Acute and chronic cigarette smoke exposure
      led to increased frequency of lung dendritic cells. Accumulation and activation
      of dendritic cells was IL-1R1/IL-1alpha dependent, but TLR4- and IL-1beta
      independent. Corroborating the cellular data, expression of CCL20, a potent
      dendritic cells chemoattractant, was IL-1R1/IL-1alpha-dependent. Studies using IL
      1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung
      structural cells for CCL20 expression. Consistent with the importance of
      dendritic cells in T cell activation, we observed decreased CD4+ and CD8+ T cell
      activation in cigarette smoke-exposed IL-1R1-deficient mice. CONCLUSION: Our
      findings convey the importance of IL-1R1/IL-1alpha to the recruitment and
      activation of dendritic cells in response to cigarette smoke exposure.

PMID- 22992202
TI  - Validation of PqsD as an anti-biofilm target in Pseudomonas aeruginosa by
      development of small-molecule inhibitors.
AB  - 2-Heptyl-4-hydroxyquinoline (HHQ) and Pseudomonas quinolone signal (PQS) are
      involved in the regulation of virulence factor production and biofilm formation
      in Pseudomonas aeruginosa. PqsD is a key enzyme in the biosynthesis of these
      signal molecules. Using a ligand-based approach, we have identified the first
      class of PqsD inhibitors. Simplification and rigidization led to fragments with
      high ligand efficiencies. These small molecules repress HHQ and PQS production
      and biofilm formation in P. aeruginosa. This validates PqsD as a target for the
      development of anti-infectives.

PMID- 22992203
TI  - Peritoneal adhesion: it can be life-threatening, and life-saving.
AB  - BACKGROUND: The inevitable post-inflammatory fibrosis and adhesion often
      compromises future treatment in peritoneal dialysis patients. Here, we describe a
      patient who experienced an unusual form of peritoneal adhesion that made her give
      up peritoneal dialysis. However, its unique pattern also saved her from infection
      caused by bowel perforation. CASE PRESENTATION: The female patient discontinued
      peritoneal dialysis due to gradual dialysis inadequacy. Two months after shifting
      to hemodialysis with generally improved sense of well-being and no sign of
      abdominal illness, she was admitted to remove the Tenckhoff catheter. The
      procedure was smooth, but fever and abdominal pain not at the site of operation
      developed the next day. Abdominal ultrasound showed the presence of ascites and
      aspiration revealed slimy, green-yellowish pus that gave a negative result on
      bacterial culture. Abdominal computed tomography (CT) with oral contrast medium
      was performed, but failed to demonstrate the suspected bowel perforation. The
      examination, however, did show accumulation of pus inside the abdomen but outside
      the peritoneal cavity. We drained the pus with two 14-F Pig-tail catheters and
      the total amount of drainage approached 4000 ml. The second CT was performed with
      double dose of the contrast medium and found a leak of the contrast from the
      jejunum. She then received laparotomy and had the perforation site closed.
      CONCLUSIONS: In summary, this uremic patient suffered from pus accumulation
      inside her abdomen without obvious systemic toxic effect. The bowel perforation
      and pus formation might be caused by repeated peritonitis, but the peritoneal
      adhesion itself might also isolate her peritoneal cavity from the anticipated
      toxic injuries of bowel perforation.

PMID- 22992204
TI  - Molecular characterization of clinical and environmental isolates of Legionella
      pneumophila in Norway, 2001-2008.
AB  - BACKGROUND: The aims of the study were to determine the molecular characteristics
      of a collection of Legionella pneumophila isolates from 45 cases with
      Legionnaires' disease and from 96 environmental samples, received by the national
      reference laboratory in Norway between 2001 and 2008, to use these
      characteristics to identify links between cases and suspected sources of
      infection, and to compare the isolate characteristics with those in other
      European countries. METHODS: The isolates were characterized by 7-gene locus
      sequence-based typing and dot-blotting with monoclonal antibodies to various
      serogroups and subgroups. RESULTS: The clinical isolates represented 12.6% of the
      357 cases notified in Norway between 2001 and 2008, during which 3 outbreaks of
      L. pneumophila serogroup 1 occurred. Outbreak cases constituted 62.2% of the
      cases, followed by travel-associated (24.4%) and sporadic cases (11.1%). Forty
      two (93.3%) of the clinical and 69 (71.9%) of the environmental isolates were
      serogroup 1, and 39 (86.7%) and 50 (52.1%) isolates, respectively, carried the
      monoclonal antibody (Mab) 3/1 virulence-associated epitope. The clinical isolates
      belonged to 17 sequence types and the environmental isolates to 19 sequence
      types. neuA was not detected in 23 environmental isolates. CONCLUSIONS: Matching
      characteristics of sequence types and monoclonal subgroups for case and
      environmental isolates were obtained for all 3 outbreaks and for 2 of 5 cases of
      sporadic disease. Sampling during the outbreaks accounted for the higher
      proportion of serogroup 1 and Mab 3/1-positive environmental isolates in
      comparison with other European strain collections.

PMID- 22992205
TI  - Assessment of retinal and choroidal blood flow changes using laser Doppler
      flowmetry in rats.
AB  - PURPOSE: A new noninvasive laser Doppler flowmetry (LDF) probe (one emitting
      fiber surrounded by a ring of eight collecting fibers, 1-mm interaxis distance)
      was tested for its sensitivity to assess the retinal/choroidal blood flow
      variations in response to hypercapnia, hyperoxia, diverse vasoactive agents and
      following retinal arteries photocoagulation in the rat. MATERIALS AND METHODS:
      After pupil dilation, a LDF probe was placed in contact to the cornea of
      anesthetized rats in the optic axis. Hypercapnia and hyperoxia were induced by
      inhalation of CO(2) (8% in medical air) and O(2) (100%) while pharmacological
      agents were injected intravitreously. The relative contribution of the choroidal
      circulation to the LDF signal was estimated after retinal artery occlusion by
      photocoagulation. RESULTS: Blood flow was significantly increased by hypercapnia
      (18%), adenosine (14%) and sodium nitroprusside (16%) as compared to baseline
      values while it was decreased by hyperoxia (-8%) and endothelin-1 (-11%).
      Photocoagulation of retinal arteries significantly decreased blood flow level (
      45%). CONCLUSIONS: Although choroidal circulation most likely contributes to the
      LDF signal in this setting, the results demonstrate that LDF represents a
      suitable in vivo noninvasive technique to monitor online relative reactivity of
      retinal perfusion to metabolic or pharmacological challenge. This technique could
      be used for repeatedly assessing blood flow reactivity in rodent models of ocular
      diseases.

PMID- 22992207
TI  - Oxidative cleavage of alpha-aryl aldehydes using iodosylbenzene.
AB  - We found that alpha-aryl aldehydes can be cleaved to chain-shortened carbonyl
      compounds and formaldehyde by various iodosylbenzene complexes. A mechanistic
      scheme is presented that accounts for the loss of one carbon atom. Formaldehyde
      is further oxidized to CO and CO(2) under the reaction conditions.

PMID- 22992206
TI  - Effects of Zn deficiency, antioxidants, and low-dose radiation on diabetic
      oxidative damage and cell death in the testis.
AB  - Infertility is one of the common complications in diabetic men and mainly due to
      the loss of germ cells by apoptotic cell death. Although several mechanisms have
      been proposed to explain the induction of testicular cell death by diabetes,
      diabetic induction of testicular oxidative stress and damage may be the
      predominant mechanism responsible for the testicular cell death in diabetes. To
      explore whether factors that either increase or decrease the testicular oxidative
      stress and damage will enhance or prevent diabetes-induced testicular cell death,
      the effect of zinc (Zn) deficiency on diabetes-induced cell death has been
      examined since Zn was found to play an important role in the protection of testis
      from oxidative stress and damage. Zn deficiency, induced by its chelator N,N,N,N
      Tetrakis(2-pyridylmethyl)-1,2-ethylenediamine, was found to exacerbate diabetes
      induced testicular oxidative damage and cell death. In contrast, treatment of
      diabetic rats with antioxidant N-acetylcysteine or low-dose radiation that can up
      regulate endogenous antioxidants significantly attenuated diabetes-induced
      testicular cell death. These results suggest that diabetes-induced testicular
      cell death that may eventually cause men's infertility is predominantly mediated
      by the oxidative stress and damage. To prevent or delay diabetes-caused
      infertility, diabetic patients should avoid Zn deficiency, and might consider
      antioxidant supplementation.

PMID- 22992208
TI  - Parafoveal processing across different lexical constituents in Chinese reading.
AB  - We report a boundary paradigm eye movement experiment to investigate whether the
      linguistic category of a two-character Chinese string affects how the second
      character of that string is processed in the parafovea during reading. We
      obtained clear preview effects in all conditions but, more importantly, found
      parafoveal-on-foveal effects whereby a nonsense preview of the second character
      influenced fixations on the first character. This effect occurred for
      monomorphemic words, but not for compound words or phrases. Also, in a word
      boundary demarcation experiment, we demonstrate that Chinese readers are not
      always consistent in their judgements of which characters in a sentence
      constitute words. We conclude that information regarding the combinatorial
      properties of characters in Chinese is used online to moderate the extent to
      which parafoveal characters are processed.

PMID- 22992210
TI  - Antibiotics for sore throat patients--varied opinions.

PMID- 22992209
TI  - On residents' satisfaction with community health services after health care
      system reform in Shanghai, China, 2011.
AB  - BACKGROUND: Health care system reform is a major issue in many countries and
      therefore how to evaluate the effects of changes is incredibly important. This
      study measured residents' satisfaction with community health care service in
      Shanghai, China, and aimed to evaluate the effect of recent health care system
      reform. METHODS: Face-to-face interviews were performed with a stratified random
      sample of 2212 residents of the Shanghai residents using structured
      questionnaires. In addition, 972 valid responses were retrieved from internet
      contact. Controlling for sex, age, income and education, the study used logistic
      regression modeling to analyze factors associated with satisfaction and to
      explain the factors that affect the residents' satisfaction. RESULTS: Comparing
      current attitudes with those held at the initial implementation of the reform in
      this investigation, four dimensions of health care were analyzed: 1) the health
      insurance system; 2) essential drugs; 3) basic clinical services; and 4) public
      health services. Satisfaction across all dimensions improved since the reform was
      initiated, but differences of satisfaction level were found among most dimensions
      and groups. Residents currently expressed greater satisfaction with clinical
      service (average score=3.79, with 5 being most satisfied) and the public
      health/preventive services (average score=3.62); but less satisfied with the
      provision of essential drugs (average score=3.20) and health insurance schemes
      (average score=3.23). The disadvantaged groups (the elderly, the retired, those
      with only an elementary education, those with lower incomes) had overall poorer
      satisfaction levels on these four aspects of health care (P<0.01). 25.39% of the
      respondents thought that their financial burden had increased and 38.49% thought
      that drugs had become more expensive. CONCLUSION: The respondents showed more
      satisfaction with the clinical services (average score=3.79) and public health
      services/interventions (average score=3.79); and less satisfaction with the
      health insurance system (average score=3.23) and the essential drug system
      (average score=3.20). Disadvantaged groups showed lower satisfaction levels
      overall relative to non-disadvantaged groups.

PMID- 22992211
TI  - Online semi-supervised growing neural gas.
AB  - In this paper we introduce online semi-supervised growing neural gas (OSSGNG), a
      novel online semi-supervised classification approach based on growing neural gas
      (GNG). Existing semi-supervised classification approaches based on GNG require
      that the training data is explicitly stored as the labeling is performed a
      posteriori after the training phase. As main contribution, we present an approach
      that relies on online labeling and prediction functions to process labeled and
      unlabeled data uniformly and in an online fashion, without the need to store any
      of the training examples explicitly. We show that using on-the-fly labeling
      strategies does not significantly deteriorate the performance of classifiers
      based on GNG, while circumventing the need to explicitly store training examples.
      Armed with this result, we then present a semi-supervised extension of GNG
      (OSSGNG) that relies on the above mentioned online labeling functions to label
      unlabeled examples and incorporate them into the model on-the-fly. As an
      important result, we show that OSSGNG performs as good as previous semi
      supervised extensions of GNG which rely on offline labeling strategies. We also
      show that OSSGNG compares favorably to other state-of-the-art semi-supervised
      learning approaches on standard benchmarking datasets.

PMID- 22992212
TI  - A descriptive study of TB cases finding practices in the three largest public
      general hospitals in Vietnam.
AB  - BACKGROUND: A project was implemented in 2010 to improve TB notification and TB
      screening and diagnostic routines in large general hospitals. The aims of present
      study was to assess baseline TB screening and diagnostic practices in the three
      largest general hospitals in Vietnam. OBJECTIVES: To assess baseline TB screening
      and diagnostic practices in the three largest general hospitals in Vietnam.
      METHOD: The study had three elements: 1) Focus group discussions with hospital
      physicians; 2) review of hospital records and structured interviews of people who
      had a chest X-ray on any indication; and 3) record reviews and structured
      interviews of people newly diagnosed with TB. RESULTS: The most commonly reported
      diagnostic pathway for pulmonary TB was chest X-ray followed by sputum-smear
      microscopy. Among 599 individuals who had a chest X-ray performed, 391 (65.1%)
      had recorded any abnormality, significantly higher in males (73.8%) than in
      females (54.7%), (p < 0.001), and the proportion was increasing with age (p
      <0.001). Among those with abnormal chest X-ray, 245 (69.2%) were investigated
      with sputum smear microscopy, and 49 (20%) were diagnosed with TB, of which 33
      (13.5%) were smear-positive.Of 103 consecutive TB cases enrolled in the study, 92
      (90%) had chest X-ray as the initial test. Sixty-three (61.2%) fulfilled the TB
      suspect criteria based on respiratory symptoms (productive cough >2 weeks).
      CONCLUSION: Chest X-ray is the preferred first test for TB in the largest
      hospitals in Vietnam. Chest X-ray is a sensitive screening tool for TB, which
      should be followed by a confirmatory TB test. While the majority of those with
      chest X-ray abnormalities are investigated with smear-microscopy, the high sputum
      smear positivity ratio among them suggests that sputum-smear microscopy is done
      mainly for persons with quite clear TB signs or symptoms. TB screening and use of
      confirmatory diagnostic tests on wider indications seem warranted.

PMID- 22992213
TI  - Drug safety and efficacy evaluation of  sertindole  for schizophrenia.
AB  - INTRODUCTION: Despite the progress in antipsychotic treatment, modern
      antipsychotic medication is still associated with side effects, reduced
      compliance, drug discontinuation and insufficient effects on negative and
      cognitive symptoms. Sertindole is an antipsychotic compound, with high affinity
      for dopamine D(2), serotonin 5-HT(2A), 5-HT(2C) and alpha(1)-adrenergic
      receptors, which has been reintroduced in the market after extended re-evaluation
      of its safety and risk-benefit profile. AREAS COVERED: Sertindole's
      pharmacological profile, pharmacokinetics, neuophysiological properties, efficacy
      on positive, negative and cognitive symptoms and safety issues are covered in
      this article, based on a literature review from 1990 to 2012. EXPERT OPINION:
      Based on five double-blind, randomized, placebo-, haloperidol- or risperidone
      controlled studies in patients with schizophrenia, sertindole shows a comparable
      efficacy with haloperidol and risperidone on positive symptoms, while the effect
      on negative symptoms seems to be superior. Sertindole is generally well
      tolerated, but is associated with a dose-related QTc interval prolongation (+22
      ms). Risk factors for drug-induced arrhythmia, such as cardiac diseases,
      congenital long QT syndrome, prolongated QTc at baseline, etc. and drug
      interactions should be considered before prescribing sertindole. To minimize
      cardiovascular risk, regular ECG recording is required. Sertindole can be an
      important second-line option for the treatment of schizophrenia for patients
      intolerant to at least one other antipsychotic. Further comparison with other
      SGAs and investigations on subgroups (e.g., children, elderly, first-episode,
      treatment-refractory patients, etc.) are still needed for a precise understanding
      of the therapeutic benefits and its role in schizophrenia therapy.

PMID- 22992215
TI  - Colloidal quantum dots as saturable fluorophores.
AB  - Although colloidal quantum dots (QDs) exhibit excellent photostability under mild
      excitation, intense illumination makes their emission increasingly intermittent,
      eventually leading to photobleaching. We study fluorescence of two commonly used
      types of QDs under pulsed excitation with varying power and repetition rate. The
      photostability of QDs is found to improve dramatically at low repetition rates,
      allowing for prolonged optical saturation of QDs without apparent photodamage.
      This observation suggests that QD blinking is facilitated by absorption of light
      in a transient state with a microsecond decay time. Enhanced photostability of
      generic quantum dots under intense illumination opens up new prospects for
      fluorescence microscopy and spectroscopy.

PMID- 22992214
TI  - Molecular surveillance for drug-resistant Plasmodium falciparum in clinical and
      subclinical populations from three border regions of Burma/Myanmar: cross
      sectional data and a systematic review of resistance studies.
AB  - BACKGROUND: Confirmation of artemisinin-delayed parasite clearance in Plasmodium
      falciparum along the Thai-Myanmar border has inspired a global response to
      contain and monitor drug resistance to avert the disastrous consequences of a
      potential spread to Africa. However, resistance data from Myanmar are sparse,
      particularly from high-risk areas where limited health services and decades of
      displacement create conditions for resistance to spread. Subclinical infections
      may represent an important reservoir for resistance genes that confer a fitness
      disadvantage relative to wild-type alleles. This study estimates the prevalence
      of resistance genotypes in three previously unstudied remote populations in
      Myanmar and tests the a priori hypothesis that resistance gene prevalence would
      be higher among isolates collected from subclinical infections than isolates
      collected from febrile clinical patients. A systematic review of resistance
      studies is provided for context. METHODS: Community health workers in Karen and
      Kachin States and an area spanning the Indo-Myanmar border collected dried blood
      spots from 988 febrile clinical patients and 4,591 villagers with subclinical
      infection participating in routine prevalence surveys. Samples positive for P.
      falciparum 18 s ribosomal RNA by real-time PCR were genotyped for P. falciparum
      multidrug resistance protein (pfmdr1) copy number and the pfcrt K76T polymorphism
      using multiplex real-time PCR. RESULTS: Pfmdr1 copy number increase and the pfcrt
      K76 polymorphism were determined for 173 and 269 isolates, respectively. Mean
      pfmdr1 copy number was 1.2 (range: 0.7 to 3.7). Pfmdr1 copy number increase was
      present in 17.5%, 9.6% and 11.1% of isolates from Karen and Kachin States and the
      Indo-Myanmar border, respectively. Pfmdr1 amplification was more prevalent in
      subclinical isolates (20.3%) than clinical isolates (6.4%, odds ratio 3.7, 95%
      confidence interval 1.1 - 12.5). Pfcrt K76T prevalence ranged from 90-100%.
      CONCLUSIONS: Community health workers can contribute to molecular surveillance of
      drug resistance in remote areas of Myanmar. Marginal and displaced populations
      under-represented among previous resistance investigations can and should be
      included in resistance surveillance efforts, particularly once genetic markers of
      artemisinin-delayed parasite clearance are identified. Subclinical infections may
      contribute to the epidemiology of drug resistance, but determination of gene
      amplification from desiccated filter samples requires further validation when DNA
      concentration is low.

PMID- 22992216
TI  - A case of galactosemia misdiagnosed as cow's milk intolerance.
AB  - We report on a female patient affected by galactosemia in whom the diagnosis was
      obscured by the concomitant presence of manifestations suggesting a cow's milk
      intolerance. This case exemplifies the problems in reaching a correct diagnosis
      in patients with metabolic diseases.

PMID- 22992217
TI  - In vitro evaluation of anti-pathogenic surface coating nanofluid, obtained by
      combining Fe3O4/C12 nanostructures and 2-((4-ethylphenoxy)methyl)-N-(substituted
      phenylcarbamothioyl)-benzamides.
AB  - In this paper, we report the design of a new nanofluid for anti-pathogenic
      surface coating. For this purpose, new 2-((4-ethylphenoxy)methyl)-N-(substituted
      phenylcarbamothioyl)-benzamides were synthesized and used as an adsorption shell
      for Fe3O4/C12 core/shell nanosized material. The functionalized specimens were
      tested by in vitro assays for their anti-biofilm properties and biocompatibility.
      The optimized catheter sections showed an improved resistance to Staphylococcus
      aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 in vitro biofilm
      development, as demonstrated by the viable cell counts of biofilm-embedded
      bacterial cells and by scanning electron microscopy examination of the colonized
      surfaces. The nanofluid proved to be not cytotoxic and did not influence the
      eukaryotic cell cycle. These results could be of a great interest for the
      biomedical field, opening new directions for the design of film-coated surfaces
      with improved anti-biofilm properties.

PMID- 22992218
TI  - Parsimonious reconstruction of network evolution.
AB  - BACKGROUND: Understanding the evolution of biological networks can provide
      insight into how their modular structure arises and how they are affected by
      environmental changes. One approach to studying the evolution of these networks
      is to reconstruct plausible common ancestors of present-day networks, allowing us
      to analyze how the topological properties change over time and to posit
      mechanisms that drive the networks' evolution. Further, putative ancestral
      networks can be used to help solve other difficult problems in computational
      biology, such as network alignment. RESULTS: We introduce a combinatorial
      framework for encoding network histories, and we give a fast procedure that,
      given a set of gene duplication histories, in practice finds network histories
      with close to the minimum number of interaction gain or loss events to explain
      the observed present-day networks. In contrast to previous studies, our method
      does not require knowing the relative ordering of unrelated duplication events.
      Results on simulated histories and real biological networks both suggest that
      common ancestral networks can be accurately reconstructed using this parsimony
      approach. A software package implementing our method is available under the
      Apache 2.0 license at  http://cbcb.umd.edu/kingsford-group/parana. CONCLUSIONS:
      Our parsimony-based approach to ancestral network reconstruction is both
      efficient and accurate. We show that considering a larger set of potential
      ancestral interactions by not assuming a relative ordering of unrelated
      duplication events can lead to improved ancestral network inference.

PMID- 22992219
TI  - Tools to kill: genome of one of the most destructive plant pathogenic fungi
      Macrophomina phaseolina.
AB  - BACKGROUND: Macrophomina phaseolina is one of the most destructive necrotrophic
      fungal pathogens that infect more than 500 plant species throughout the world. It
      can grow rapidly in infected plants and subsequently produces a large amount of
      sclerotia that plugs the vessels, resulting in wilting of the plant. RESULTS: We
      sequenced and assembled ~49 Mb into 15 super-scaffolds covering 92.83% of the M.
      phaseolina genome. We predict 14,249 open reading frames (ORFs) of which 9,934
      are validated by the transcriptome. This phytopathogen has an abundance of
      secreted oxidases, peroxidases, and hydrolytic enzymes for degrading cell wall
      polysaccharides and lignocelluloses to penetrate into the host tissue. To
      overcome the host plant defense response, M. phaseolina encodes a significant
      number of P450s, MFS type membrane transporters, glycosidases, transposases, and
      secondary metabolites in comparison to all sequenced ascomycete species. A
      strikingly distinct set of carbohydrate esterases (CE) are present in M.
      phaseolina, with the CE9 and CE10 families remarkably higher than any other
      fungi. The phenotypic microarray data indicates that M. phaseolina can adapt to a
      wide range of osmotic and pH environments. As a broad host range pathogen, M.
      phaseolina possesses a large number of pathogen-host interaction genes including
      those for adhesion, signal transduction, cell wall breakdown, purine
      biosynthesis, and potent mycotoxin patulin. CONCLUSIONS: The M. phaseolina genome
      provides a framework of the infection process at the cytological and molecular
      level which uses a diverse arsenal of enzymatic and toxin tools to destroy the
      host plants. Further understanding of the M. phaseolina genome-based plant
      pathogen interactions will be instrumental in designing rational strategies for
      disease control, essential to ensuring global agricultural crop production and
      security.

PMID- 22992220
TI  - Airway protease/antiprotease imbalance in atopic asthmatics contributes to
      increased influenza A virus cleavage and replication.
AB  - Asthmatics are more susceptible to influenza infections, yet mechanisms mediating
      this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA)
      protein binds to sialic acid residues on the host cells. HA requires cleavage to
      allow fusion of the viral HA with host cell membrane, which is mediated by host
      trypsin-like serine protease. We show data here demonstrating that the
      protease:antiprotease ratio is increased in the nasal mucosa of asthmatics and
      that these changes were associated with increased proteolytic activation of
      influenza. These data suggest that disruption of the protease balance in
      asthmatics enhances activation and infection of influenza virus.

PMID- 22992221
TI  - FOXP3-marked IL-17a-producing regulatory T cells are increased in patients with
      allergic rhinitis.
AB  - CONCLUSION: The deficient regulatory T cells may play a role in the development
      of allergic rhinitis. OBJECTIVE: A subpopulation of regulatory T cell that
      produce IL-17a were proved to show an apparent duality of regulatory T cell and
      effector T helper-17 cells. We studied this subpopulation in patients with
      allergic rhinitis. METHODS: Fresh whole blood from 20 patients with allergic
      rhinitis and 19 healthy donors was used to investigate the frequencies of
      CD4(+)IFN-gamma(+) T cells (effector T helper-1), CD4(+)IL-4(+) T cells (effector
      T helper-2) and CD4(+)IL-17a(+) T cells (effector T helper-17) by flow cytometry
      after stimulation for 4-6 h. Simultaneously, CD4(+) T lymphocytes were isolated
      from peripheral blood mononuclear cells and then the frequencies of regulatory T
      cells and IL-17a-producing regulatory T cells in the allergic rhinitis group were
      compared with healthy controls after T-cell antigen receptor stimulation for 48
      h. The suppressive capacity of CD4(+)CD25(high)CD127(low) regulatory T cells that
      were stimulated by Dermatophagoides pteronyssinus in both groups was isolated and
      assessed. RESULTS: The frequencies of effector T helper-17 and effector T helper
      2 cells were higher in the allergic group compared with healthy controls.
      Regulatory T cells were similar in both groups, but IL-17a-producing regulatory T
      cells were increased in the allergic group. In addition, the capacity of
      regulatory T cells to suppress effector T helper-17 cytokine production was
      significantly decreased in the allergic group.

PMID- 22992222
TI  - Measuring patient experiences in Fabry disease: validation of the Fabry-specific
      Pediatric Health and Pain Questionnaire (FPHPQ).
AB  - INTRODUCTION: Common symptoms for children with Anderson-Fabry Disease (FD) such
      as acroparaesthesia and gastrointestinal manifestations can only be objectively
      assessed in patients using a valid instrument. To date, no such instrument
      exists. METHODS: A preliminary 40-item measure of symptoms and experience with
      FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was
      developed, but lacked a formal assessment of its measurement properties. The
      FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients
      with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are
      treatment naive and who are managed by physicians participating in FOS. After an
      item analysis to explore how items performed and combined into domains, a battery
      of psychometric analyses was performed to assess the measurement properties of
      this new instrument. RESULTS: Eighty-seven children (ages 4-18 years) completed
      the questionnaire. Twenty-three items in three subscales of the questionnaire
      emerged: pain associated with heat or exertion, pain associated with cold, and
      abdominal pain and fatigue symptoms. Internal consistency reliability for all
      three subscales was good (Cronbach alpha >= 0.84). Reliability was equally high
      for all age groups (4-7, 8-12, and 13-18). Test-retest reliability was high for
      all three subscales (intraclass correlation coefficient >= 0.74). Construct
      validity was demonstrated by moderate correlation with brief pain inventory
      (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to
      discriminate between Fabry disease severity groups as classified by above or
      below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or
      exertion subscale was responsive to change in symptoms between responders and non
      responders as defined by change in EQ-5D index scores between the first and
      second visit. CONCLUSIONS: Preliminary results indicate that the measurement
      properties of FPHPQ are valid and reliable for assessing patient-reported
      symptoms of FD. The questionnaire could be a useful tool for clinicians to
      understand the progression of disease and monitor treatment effects. FPHPQ will
      be further validated and refined as the FOS registry is continuously adding more
      patients.

PMID- 22992223
TI  - Enzymatic control of plasmonic coupling and surface enhanced Raman scattering
      transduction for sensitive detection of DNA demethylation.
AB  - We have developed a novel concept for enzymatic control of plasmonic coupling as
      a surface enhanced Raman scattering (SERS) nanosensor for DNA demethylation. This
      nanosensor is constructed by decorating gold nanoparticles (AuNPs) with Raman
      reporters and hemimethylated DNA probes. Demethylation of DNA probes initiates a
      degradation reaction of the probes by methylation-sensitive endonuclease Bsh
      1236I and single-strand selective exonuclease I. This destabilizes AuNPs and
      mediates the aggregation of AuNPs, generating a strong plasmonic coupling SERS
      signal in response to DNA demethylation. This nanosensor has the advantages in
      its high signal-to-noise ratio, superb specificity, and rapid, convenient, and
      reproducible detection with homogeneous, single-step operation. Thus, it provides
      a useful platform for detecting DNA demethylation and related molecular
      diagnostics and drug screening. This work is the first time that enzymatic
      degradation of DNA substrate probes has been utilized to induce aggregation of
      AuNPs such that reproducible, sensitive SERS signals can be achieved from
      biological recognition events. This enzymatic control mechanism for plasmonic
      coupling may create a new paradigm for the development of SERS nanosensors.

PMID- 22992224
TI  - Computational and experimental analyses reveal the essential roles of interdomain
      linkers in the biological function of chemotaxis histidine kinase CheA.
AB  - A two-component signal transduction pathway underlies the phenomenon of bacterial
      chemotaxis that allows bacteria to modulate their swimming behavior in response
      to environmental stimuli. The dimeric five-domain histidine kinase, CheA, plays a
      central role in the pathway, converting sensory signals to a chemical signal via
      trans-autophosphorylation between the P1 and P4 domains. This autophosphorylation
      is regulated via the networked interactions among the P5 domain of CheA, CheW,
      and chemoreceptors. Despite a wealth of structural information about these
      components and their interactions, the key question of how the kinase activity of
      the catalytic P4 domain is regulated by the signal received from the regulatory
      P5 domain remains poorly understood. We performed replica exchange molecular
      dynamics simulations on the CheA kinase core and found that while individual
      domains maintained their structural fold, these domains exhibited a variety of
      interdomain orientations due to two interdomain linkers. A partially populated
      conformation that adopts an interdomain arrangement is suitable for building a
      functional ternary complex. An allosteric network derived from this structural
      model implies critical roles for two linkers in CheA's activity. The biochemical
      and biological functions of these linkers were assigned via a series of
      biochemical and genetic assays that show the P4-P5 linker controls the activation
      of CheA and the P3-P4 linker controls both the basal autophosphorylation activity
      and the activation of CheA. These results reveal the functional dependence
      between the two linkers and the essential role of the linkers in passing signal
      information from one domain to another.

PMID- 22992225
TI  - "Looking back to my family": indigenous Australian patients' experience of
      hemodialysis.
AB  - BACKGROUND: In common with Indigenous populations elsewhere, Indigenous
      Australians have higher incidence of end-stage kidney disease (ESKD), but lower
      transplantation rates than their non-Indigenous counterparts. Understanding how
      the demands of dialysis impact on, and are impacted by, the lives of Indigenous
      patients may provide important insight into treatment pathways and decision
      making. METHODS: We conducted semi-structured interviews in 2005-06 with 146
      Indigenous and 95 non-Indigenous patients from nine hospital renal wards and 17
      associated dialysis centres, which together treat the majority of Indigenous
      Australian ESKD patients. RESULTS: Factors influencing treatment experience
      included: the impacts of late diagnosis; family separations associated with
      relocating for treatment; the physical and psychosocial demands of hemodialysis;
      and ineffective communication between health care providers and patients.
      Although not unique to them, Indigenous patients were more likely to experience
      the combined effect of all factors. CONCLUSIONS: Social/situational circumstances
      profoundly affect Indigenous Australian dialysis patients' ability to fully
      engage with treatment. This may ultimately affect their likelihood of receiving
      optimal treatment, including transplantation. Areas for improvement include:
      earlier diagnosis; improved linkages between specialist renal services and
      primary care in regional settings; more effective communication and patient
      education; and more systematic, transparent approaches to patient "compliance" in
      transplant and home dialysis guidelines.

PMID- 22992226
TI  - Lymphatic filariasis among the Yakurr people of Cross River State, Nigeria.
AB  - BACKGROUND: In order to initiate a disease elimination programme for lymphatic
      filariasis based on mass drug administration, a proper understanding of the
      geographical distribution and degree of risk is essential. METHODS: An
      investigation of lymphatic filariasis due to Wuchereria bancrofti was carried out
      among 785 people in four communities of Yakurr Local Government Area of Cross
      River State, Nigeria between March and August, 2009. Finger prick blood smear
      samples collected from the subjects were examined for W. bancrofti using standard
      parasitological protocol. The subjects were also screened for clinical
      manifestations of lymphatic filariasis. RESULTS: Of the 785 persons examined, 48
      (6.1%) were positive for microfilariae in their thick blood smear. There was a
      significant difference in the prevalence of lymphatic filariasis among the
      various age groups (P < 0.01) although peak prevalence occurred between 41-60
      years. There was no significant difference in prevalence and density with respect
      to sex (P > 0.05). The overall mean microfilarial density of the infected
      individuals was 5.6 mf/50 MUl. There was a significant variation (P < 0.01) in
      mean microfilarial density within the communities, ranging from 4.7 to 6.4 mf/50
      MUl. The only clinical sign found in the study area was lymphoedema of the leg
      recording 2 (0.3%) prevalence. CONCLUSIONS: The National Lymphatic Filariasis
      Elimination Programme should intervene by expanding the distribution of
      albendazole and ivermectin to all endemic areas including Yakurr Local Government
      Area of Cross River State, Nigeria.

PMID- 22992227
TI  - Ligninolytic enzymes from Ganoderma spp: current status and potential
      applications.
AB  - White-rot fungal species belonging to Ganoderma have long been used as medicinal
      mushrooms in many Asian countries. In recent years, however, attention is not
      just being paid to their pharmacological properties, but to their other
      potentially valuable features as well, including their secretion of enzymes which
      decompose lignin. The current literature regarding lignin-modifying enzymes from
      the genus Ganoderma, their potential uses, and the components, structures and
      processes of lignocellulose degradation are discussed. The ligninolytic enzymes
      from the genus Ganoderma, as well as the number of additional enzymes that
      participate in lignin degradation, are summarized; further, the potential
      applications of these enzymes are analyzed and probed in this article. This
      review will provide insight on the valuable applications of Ganoderma spp. and
      will serve as a useful reference on the use of lignocellulose degradation as a
      means of environmental protection. 

PMID- 22992228
TI  - Blastic plasmacytoid dendritic cell neoplasm: is it time to redefine the standard
      of care?

PMID- 22992230
TI  - Role of carfilzomib in the treatment of multiple myeloma.
AB  - The introduction of bortezomib, a first-generation proteasome inhibitor, changed
      the standard-of-care for newly diagnosed and relapsed multiple myeloma patients.
      The next generation of proteasome inhibitors, such as carfilzomib, provides a
      novel pharmacokinetic and pharmacodynamic profile. In vitro data suggest a more
      specific and irreversible inhibition of the proteasome. Based on the clinical
      trials conducted to date, carfilzomib has activity in heavily pretreated as well
      as bortezomib-refractory/relapsed patients. The safety profile, specifically a
      lower incidence of peripheral neuropathy, efficacy in the high-risk setting, as
      defined cytogenetically, and the durability of responses indicate a great
      potential for carfilzomib as a promising therapy. Several trials are underway
      involving carfilzomib in the newly diagnosed setting and in combination with
      other active myeloma drugs such as immunomodulatory derivatives of thalidomide,
      alkylating agents and targeted therapies such as histone deacetylase inhibitors.
      The introduction of this agent is yet another step in improving the overall
      outcome of multiple myeloma patients.

PMID- 22992231
TI  - A clinical algorithm predicts hematological complications in Shwachman-Diamond
      syndrome?
AB  - Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by
      mutations in the SBDS gene in approximately 90% of cases. SDS is characterized by
      exocrine pancreatic insufficiency and bone marrow failure, which predisposes to
      the development of myelodysplastic syndrome and/or acute myeloid leukemia. In a
      new report, the French national cohort studied 102 SDS patients with a median
      follow-up of 11.6 years, focusing on the natural history of severe cytopenias.
      The authors concluded that SDS patients with a young age (<3 months) at first
      symptomatic presentation or cytopenia at diagnosis were at a high risk of
      subsequent severe hematological complications (either malignant or nonmalignant).
      Their findings raise the possibility that a clinical algorithm may predict the
      subsequent development of hematological complications in SDS.

PMID- 22992232
TI  - Prediction of clopidogrel efficacy and safety: phenotyping and/or genotyping?
AB  - In patients undergoing percutaneous coronary intervention the role of platelet
      function assessment (phenotyping) while on-clopidogrel and/or genotyping for
      outcome prediction is being intensively investigated. The study under evaluation
      reported the diagnostic accuracy of phenotyping versus genotyping for prediction
      of ischemic and bleeding events in 416 such patients during 1-year follow-up.
      Their data shows that the phenotyping of platelet response to clopidogrel by
      multiple electrode aggregometry was a better predictor of stent thrombosis than
      other platelet function assays used and even genotyping for the CYP2C19*2 allele.
      The authors recognize that it is premature to recommend any assay to guide the
      antiplatelet treatment in routine clinical practice. However, the need for
      properly powered randomized trials to address this issue is emphasized.

PMID- 22992233
TI  - Chromosomal aberrations and fusion genes in myeloid malignancies.
AB  - Since the discovery of the BCR-ABL1 fusion gene in chronic myeloid leukemia, many
      more fusion genes resulting from chromosomal rearrangements have been identified
      and characterized. The study of these fusion genes has been extremely important
      for our understanding of the role of chromosomal rearrangements in leukemogenesis
      and in oncology in general. In chronic myeloid leukemia, or related
      myeloproliferative malignancies caused by the expression of oncogenic fusion
      kinases, tyrosine kinase inhibitors are now successfully used to treat these
      diseases. In acute myeloid leukemias, the presence of chromosomal rearrangements,
      oncogenic fusion genes and point mutations in key oncogenic drivers has important
      prognostic value and determines the choice of therapy. In this review, the
      authors provide an overview of the important fusion genes present in various
      myeloid malignancies and their importance for clinical practice.

PMID- 22992234
TI  - Genetic biomarkers in acute myeloid leukemia: will the promise of improving
      treatment outcomes be realized?
AB  - Recent progress in the molecular genetics of acute myeloid leukemia (AML) has
      shown this disease to be more heterogeneous than previously realized. Recurrent
      cytogenetic and mutational changes in leukemic blasts have been confirmed to have
      high prognostic significance. High-throughput techniques to analyze the AML
      genome in greater depth have revealed novel mutations with putative roles in
      leukemogenesis. The use of prognostic biomarkers has allowed for a more detailed
      categorization of AML based on risk. Despite this tremendous progress, the
      understanding of the mechanisms by which these changes influence leukemia growth
      and response to treatment is still limited, which in turn has hindered the
      development of rationally targeted therapies for AML. The integration of
      clinical, cytogenetic and molecular data will be essential to translate the
      current research momentum into better outcomes for patients with AML.

PMID- 22992236
TI  - Hematologic malignancies associated with germ cell tumors.
AB  - Germ cell tumor (GCT)-associated hematologic malignancies present a unique
      challenge to hematologists and hematopathologists. As most GCTs are of gonadal
      origin, only a small percentage occur at extragonadal sites in the midline.
      Extragonadal GCTs are believed to originate from the ectopic primordial germ
      cells that fail to migrate to the urogenital ridge during development. An
      overactive KIT pathway and overexpression of genes on chromosome 12p are strongly
      implicated in GCT development. Approximately 54% of extragonadal GCTs are located
      in the anterior mediastinum. This is disproportionally high among the midline
      structures, presumably due to a favorable microenvironment for GCT development in
      the developing thymus. The mediastinal nonseminomatous GCTs have two unique
      features. First, they are often refractory to current treatment modality with the
      worst prognosis among GCTs of all sites. Second, they have a tendency to give
      rise to secondary hematologic neoplasia. The outcome is grave for patients with
      GCT-associated hematologic malignancies. As standard chemotherapy used to treat
      their bone marrow-derived counterparts has been ineffective, the best treatment
      modality to achieve long-term survival is allogeneic hematopoietic stem cell or
      cord blood transplant for a very limited number of cases.

PMID- 22992237
TI  - Metabolic syndrome in patients with hematological diseases.
AB  - The term metabolic syndrome (MS) defines a clustering of cardiovascular risk
      factors, formerly known as syndrome X. There is some debate about the diagnostic
      criteria; but the most widely accepted framework is that defined by the National
      Cholesterol Education Program Adult Treatment Panel III, which requires the
      simultaneous occurrence of at least three of abdominal obesity, arterial
      hypertension, hyperglycemia, hypertrigliceridemia and low high-density
      lipoprotein cholesterol (HDL-C). The prevalence of MS increases with age and
      varies depending on genetic factors. An abnormally high prevalence has been
      observed in patients with heterogeneous conditions, such as solid organ
      transplant recipients, AIDS patients and long-term cancer survivors. As some of
      the pathogenetic factors possibly involved include cyclosporine A,
      corticosteroids and cancer chemoradiotherapy, it is possible that MS may also be
      a complication in hematological patients. Some of the characteristics of MS have
      been reported with a certain frequency in thalassemia patients, and are mainly
      attributed to iron overload. Impaired hemostasis is a feature of MS rather than a
      factor predisposing to its development. In oncohematology, an abnormally high
      prevalence of MS features has been observed in survivors of pediatric acute
      lymphoblastic leukemia. In addition to corticosteroid- and cancer therapy-related
      hypogonadism, hypothyroidism and defective growth hormone incretion are other
      factors related to the development of MS. Moreover, the highest frequency of MS
      is observed in hematopoietic stem cell transplantation (HSCT) recipients.
      Pediatric patients and allogeneic HSCT recipients have been the subject of
      foremost investigations; but adult patients and autologous HSCT recipients have
      also been studied more recently. A wide range of factors may contribute to the
      development of MS in HSCT recipients. Unfortunately, the real entity of the
      problem is far from clear because of the retrospective design of the studies, the
      limited size of their populations and their heterogeneous selection criteria,
      thus making it difficult to determine whether MS is a transient and possibly
      reversible phenomenon or a true late effect of the procedure.

PMID- 22992238
TI  - Management of joint bleeding in hemophilia.
AB  - Hemarthrosis, the hallmark of severe hemophilia, is the major cause of serious
      bleeding events, disability and reduced quality of life in patients with factor
      VIII or factor IX deficiency. Joint bleeding is one of the greatest challenges
      confronting individuals treating hemophilia, and its economic impact is enormous.
      This article reviews the current management of hemophilic joint bleeding and
      discusses the potential impact of novel therapies.

PMID- 22992240
TI  - Development, effectiveness and cost-effectiveness of a new out-patient
      Breathlessness Support Service: study protocol of a phase III fast-track
      randomised controlled trial.
AB  - BACKGROUND: Breathlessness is a common and distressing symptom affecting many
      patients with advanced disease both from malignant and non-malignant origin. A
      combination of pharmacological and non-pharmacological measures is necessary to
      treat this symptom successfully. Breathlessness services in various compositions
      aim to provide comprehensive care for patients and their carers by a
      multiprofessional team but their effectiveness and cost-effectiveness have not
      yet been proven. The Breathlessness Support Service (BSS) is a newly created
      multiprofessional and interdisciplinary outpatient service at a large university
      hospital in South East London. The aim of this study is to develop and evaluate
      the effectiveness and cost effectiveness of this multidisciplinary out-patient
      BSS for the palliation of breathlessness, in advanced malignant and non-malignant
      disease. METHODS: The BSS was modelled based on the results of qualitative and
      quantitative studies, and systematic literature reviews. A randomised controlled
      fast track trial (RCT) comprising two groups: 1) intervention (immediate access
      to BSS in addition to standard care); 2) control group (standard best practice
      and access to BSS after a waiting time of six weeks). Patients are included if
      suffering from breathlessness on exertion or at rest due to advanced disease such
      as cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure
      (CHF), interstitial lung disease (ILD) or motor neurone disease (MND) that is
      refractory to maximal optimised medical management. Both quantitative and
      qualitative outcomes are assessed in face to-face interviews at baseline, after 6
      and 12 weeks. The primary outcome is patients' improvement of mastery of
      breathlessness after six weeks assessed on the Chronic Respiratory Disease
      Questionnaire (CRQ). Secondary outcomes for patients include breathlessness
      severity, symptom burden, palliative care needs, service use, and respiratory
      measures (spirometry). For analyses, the primary outcome, mastery of
      breathlessness after six weeks, will be analysed using ANCOVA. Selection of
      covariates will depend on baseline differences between the groups. Analyses of
      secondary outcomes will include patients' symptom burden other than
      breathlessness, physiological measures (lung function, six minute walk distance),
      and caregiver burden. DISCUSSION: Breathlessness services aim to meet the needs
      of patients suffering from this complex and burdensome symptom and their carers.
      The newly created BSS is different to other current services as it is run in
      close collaboration of palliative medicine and respiratory medicine to optimise
      medical care of patients. It also involves professionals from various medical,
      nursing, physiotherapy, occupational therapy and social work background. TRIAL
      REGISTRATION: ClinicalTrials.gov (NCT01165034).

PMID- 22992235
TI  - Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic
      hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HCT) is currently the
      standard of care for most patients with high-risk acute leukemias and some other
      hematologic malignancies. Although HCT can be curative, many patients who undergo
      allogeneic HCT will later relapse. There is, therefore, a critical need for the
      development of novel post-HCT therapies for patients who are at high risk for
      disease recurrence following HCT. One potentially efficacious approach is
      adoptive T-cell immunotherapy, which is currently undergoing a renaissance that
      has been inspired by scientific insight into the key issues that impeded its
      previous clinical application. Translation of the next generation of adoptive T
      cell therapies to the allogeneic HCT setting, using donor T cells of defined
      specificity and function, presents a unique set of challenges and opportunities.
      The challenges, progress and future of adoptive T-cell therapy following
      allogeneic HCT are discussed in this review.

PMID- 22992244
TI  - [Malnutrition in patients with cancer].
AB  - Malnutrition is a condition characterized by a shortage or imbalance of energy
      and proteins and/or other nutrients. Malnutrition leads to measurable undesirable
      effects on body size and composition, functioning and clinical results. Criteria
      for malnutrition are eight loss, low BMI and loss of muscle mass. Patients with
      cancer should be repeatedly screened for malnutrition and its risk factors during
      the diagnostic and therapeutic treatment trajectory. Patients with cancer who are
      malnourished or are at risk of becoming so should be referred to a dietician for
      individualized dietary advice if they are undergoing curative treatment or before
      they do so. At the start of radiotherapy and/or chemotherapy treatment, tube
      feeding or parenteral feeding is given to all cancer patients who are
      malnourished or are at high risk of becoming malnourished. If the
      gastrointestinal tract is functioning well then tube feeding is preferable to
      parenteral feeding. Patients who are at an advanced stage of cancer and cancer
      patients who are anorexic or lose weight can be treated with megastrol acetate.

PMID- 22992241
TI  - Gender differences in disordered eating and weight dissatisfaction in Swiss
      adults: which factors matter?
AB  - BACKGROUND: Research results from large, national population-based studies
      investigating gender differences in weight dissatisfaction and disordered eating
      across the adult life span are still limited. Gender is a significant factor in
      relation to weight dissatisfaction and disordered eating. However, the reasons
      for gender differences in these conditions are still poorly understood. The aim
      of this study was to examine gender differences in weight dissatisfaction and
      disordered eating in the general Swiss adult population and to identify gender
      specific risk factors. METHODS: The study population consisted of 18156 Swiss
      adults who completed the population-based Swiss Health Survey 2007. Self-reported
      weight dissatisfaction, disordered eating and associated risk factors were
      assessed. In order to examine whether determinants of weight dissatisfaction and
      disordered eating (dieting to lose weight, binge eating, and irregular eating)
      differ in men and women, multivariate logistic regressions were applied
      separately for women and men. RESULTS: Although more men than women were
      overweight, more women than men reported weight dissatisfaction. Weight category,
      smoking status, education, and physical activity were significantly associated
      with weight dissatisfaction in men and women. In women, nationality and age were
      also significant factors. Gender-specific risk factors such as physical activity
      or weight category were identified for specific disordered eating behaviours.
      CONCLUSIONS: The results suggest that gender specific associations between
      predictors and disordered eating behaviour should be considered in the
      development of effective prevention programs against disordered eating.

PMID- 22992245
TI  - [Foetal therapy for spina bifida].
AB  - Spina bifida is the most common congenital birth defect involving the central
      nervous system. It results in central and peripheral abnormalities. Patients with
      severe spina bifida may have a lifelong disability with dependence on medical and
      social supportive care. A randomized controlled trial demonstrated that, for a
      selected number of patients, prenatal closure of the defect resulted in a better
      neurological outcome than postnatal surgical repair. Prenatal surgery of spina
      bifida is associated with an increased risk of preterm birth and obstetric
      complications and is not yet considered the standard of care in the Netherlands.
      In case of a prenatal diagnosis of spina bifida, the pregnant woman is entitled
      to full information about the possibility of prenatal treatment and to a possible
      referral for this.

PMID- 22992246
TI  - [Summary of the Dutch College of General Practitioners' practice guideline
      'Depression'].
AB  - This guideline gives recommendations for the management of depression and
      depressive symptoms. The diagnosis of suspected depression requires a broad
      exploration of symptoms, sometimes over several visits. The guideline promotes
      self-management and patient empowerment during the healing process. The initial
      step in the treatment of depressive symptoms is patient education; patients with
      depression are supported with activity scheduling and are offered a short course
      of psychological treatment. If the initial treatment in patients with depression
      is not effective or if the depression is associated with severe suffering, severe
      social dysfunctioning or severe psychiatric comorbidity, psychotherapy or an
      antidepressant is recommended.

PMID- 22992247
TI  - [Hepatocellular adenomas and pregnancy].
AB  - Hepatocellular adenomas are benign liver tumours which are mostly seen in young
      women. When women with such tumours attempt to become pregnant, they require
      special attention because of the risks of hormone-induced growth and spontaneous
      rupture of the tumour, which are caused by increased levels of steroid hormones
      during pregnancy. We present three patients with hepatocellular adenomas who were
      either pregnant or wished to become pregnant. These cases describe the complexity
      of the situation. The size of the hepatocellular adenoma increased during
      pregnancy in patient A and contrarily remained stable in patient B. Patient C was
      advised to not get pregnant before an intervention because of the tumour's
      central location within the liver. We also describe the general clinical
      presentation and treatment of patients with a hepatocellular adenoma.

PMID- 22992248
TI  - [Revised Dutch GP guideline 'Depression': diagnosis not as simple as it appears].
AB  - The revised Dutch guideline on depression in primary care is excellent. However,
      there is potential for misinterpretation when counting symptoms - an essential
      part of diagnosis. In the DSM-IV twenty-one symptoms are classified into 9
      clusters. When using this guideline, it is possible to read 'decreased energy or
      tiredness', not 'and', so the 'or' leads to counting 2 symptoms instead of 1.
      Symptoms important for diagnosis include a period of at least 2 consecutive weeks
      during which mood is either depressed or there is loss of interest or pleasure in
      activities which persists for most of the day, nearly every day. This indicates
      low reactivity. If these decision rules are not properly understood too many
      diagnoses of depression may be made. The guideline pays no attention to
      personality problems, enabling patients to attribute their symptoms to problems
      of life and thus rule out their own behaviour. To make them responsible for their
      own actions in as far as this is possible, will be difficult.

PMID- 22992249
TI  - [Vancomycin-resistant enterococcus--chronicle of a foretold problem].
AB  - There have recently been 12 outbreaks of infection caused by vancomycin-resistant
      enterococci (VRE) in Dutch hospitals. Although the first VRE outbreaks were
      reported almost 12 years ago, such outbreaks remained uncommon and the question
      is why they are occurring now. Based on molecular epidemiological studies we have
      learned that a subpopulation of Enterococcus faecium, resistant to amoxicillin
      but susceptible to vancomycin, has become highly endemic in Dutch hospitals in
      the past 12 years. Initial analyses suggest that several transposons containing
      vancomycin-resistance genes have been introduced into this population, followed
      by nosocomial spread. We recommend that hospitals without detected VRE outbreaks
      screen high-risk patients for the presence of VRE. If transmission has already
      occurred in many hospitals, it will be extremely difficult (and costly) to
      eradicate VRE.

PMID- 22992250
TI  - [Malnutrition in patients with cancer: is eating enough really enough?].
AB  - The new practice guideline 'Malnutrition in patients with cancer' provides a good
      framework for the practical treatment of patients with impending cancer cachexia.
      Because the pathophysiology of cancer cachexia is multifactorial, its treatment
      requires a multimodal approach. Such multimodal treatment should probably consist
      of nutritional support in combination with physical exercise, anti-inflammatory
      medication and an anabolic or anticatabolic intervention. The aim is to control
      undesired loss of muscle and fat mass. Unfortunately, the data currently
      available are limited and do not allow evidence-based advice beyond the paradigm
      of treating malnutrition by feeding patients appropriately.

PMID- 22992251
TI  - Effect of folate intake on health outcomes in pregnancy: a systematic review and
      meta-analysis on birth weight, placental weight and length of gestation.
AB  - The beneficial effect of folic acid supplementation before and shortly after
      conception is well recognized, whereas the effect of supplementation during the
      second and third trimesters is controversial and poorly documented. Our aims were
      to systematically review randomized controlled trials (RCTs) investigating the
      effect of folate supplementation on birth weight, placental weight and length of
      gestation and to assess the dose-response relationship between folate intake
      (folic acid plus dietary folate) and health outcomes. The MEDLINE, EMBASE and
      Cochrane Library CENTRAL databases were searched from inception to February 2010
      for RCTs in which folate intake and health outcomes in pregnancy were
      investigated. We calculated the overall intake-health regression coefficient
      (beta^) by using random-effects meta-analysis on a log(e)-log(e) scale. Data of
      10 studies from 8 RCTs were analyzed. We found significant dose-response
      relationship between folate intake and birth weight (P=0.001), the overall beta^
      was 0.03 (95% confidence interval (CI): 0.01, 0.05). This relationship indicated
      2% increase in birth weight for every two-fold increase in folate intake. In
      contrast, we did not find any beneficial effect of folate supplementation on
      placental weight or on length of gestation. There is a paucity of well-conducted
      RCTs investigating the effect of folate supplementation on health outcomes in
      pregnancy. The dose-response methodology outlined in the present systematic
      review may be useful for designing clinical studies on folate supplementation and
      for developing recommendations for pregnant women.

PMID- 22992252
TI  - Two young-adult female cases of dermatomyositis with antibodies for
      transcriptional intermediary factor 1-gamma.
AB  - A variety of myositis-specific autoantibodies (MSAs) have been detected in
      patients with dermatomyositis (DM). We analyzed MSAs in 20 cases with DM. Eleven
      of the 20 cases were positive. Out of those 11 cases, 3 were positive for
      antibodies against aminoacyl-tRNA synthetase and 3 had antibodies to anti
      melanoma differentiation-associated gene 5 detected using an immunoprecipitation
      assay and/or a specific enzyme-linked immunosorbent assay. One case had anti-NXP
      2 antibodies and 4 cases had anti-transcriptional intermediary factor 1 (TIF1)
      alpha/gamma antibodies detected by immunoprecipitation and Western blotting. Two
      of those 4 cases had antibodies for both TIF1-alpha and TIF1-gamma, and the 2
      other cases had antibodies for TIF1-gamma alone. We report the 2 cases with
      antibodies for TIF1-gamma only, who were young-adult females without an internal
      malignancy or interstitial pneumonia. Those 2 cases had clinically amyopathic DM.
      Among DM patients with antibodies against TIF1 family proteins, there seems to be
      a subgroup of young-adult cases who have clinically amyopathic DM and show good
      prognosis without malignancy.

PMID- 22992253
TI  - Exciton quantum confinement in nanocones formed on a surface of CdZnTe solid
      solution by laser radiation.
AB  - The investigation of surface morphology using atomic force microscope has shown
      self-organizing of the nanocones on the surface of CdZnTe crystal after
      irradiation by strongly absorbed Nd:YAG laser irradiation at an intensity of 12.0
      MW/cm2. The formation of nanocones is explained by the presence of a
      thermogradient effect in the semiconductor. The appearance of a new exciton band
      has been observed after irradiation by the laser which is explained by the
      exciton quantum confinement effect in nanocones.

PMID- 22992254
TI  - Cleavage pattern and fate map of the mesentoblast, 4d, in the gastropod
      Crepidula: a hallmark of spiralian development.
AB  - BACKGROUND: Animals with a spiral cleavage program, such as mollusks and
      annelids, make up the majority of the superphylum Lophotrochozoa. The great
      diversity of larval and adult body plans in this group emerges from this highly
      conserved developmental program. The 4d micromere is one of the most conserved
      aspects of spiralian development. Unlike the preceding pattern of spiral
      divisions, cleavages within the 4d teloblastic sublineages are bilateral,
      representing a critical transition towards constructing the bilaterian body plan.
      These cells give rise to the visceral mesoderm in virtually all spiralians
      examined and in many species they also contribute to the endodermal intestine.
      Hence, the 4d lineage is an ideal one for studying the evolution and
      diversification of the bipotential endomesodermal germ layer in protostomes at
      the level of individual cells. Little is known of how division patterns are
      controlled or how mesodermal and endodermal sublineages diverge in spiralians.
      Detailed modern fate maps for 4d exist in only a few species of clitellate
      annelids, specifically in glossiphoniid leeches and the sludge worm Tubifex. We
      investigated the 4d lineage in the gastropod Crepidula fornicata, an established
      model system for spiralian biology, and in a closely related direct-developing
      species, C. convexa. RESULTS: High-resolution cell lineage tracing techniques
      were used to study the 4d lineage of C. fornicata and C. convexa. We present a
      new nomenclature to name the progeny of 4d, and report the fate map for the
      sublineages up through the birth of the first five pairs of teloblast daughter
      cells (when 28 cells are present in the 4d sublineage), and describe each clone's
      behavior during gastrulation and later stages as these undergo differentiation.
      We identify the precise origin of the intestine, two cells of the larval kidney
      complex, the larval retractor muscles and the presumptive germ cells, among
      others. Other tissues that arise later in the 4d lineage include the adult heart,
      internal foot tissues, and additional muscle and mesenchymal cells derived from
      later-born progeny of the left and right teloblasts. To test whether other cells
      can compensate for the loss of these tissues (that is, undergo regulation),
      specific cells were ablated in C. fornicata. CONCLUSIONS: Our results present the
      first fate map of the 4d micromere sublineages in a mollusk. The fate map reveals
      that endodermal and mesodermal fates segregate much later than previously
      thought. We observed little evidence of regulation between sublineages,
      consistent with a lineage-driven cell specification process. Our results provide
      a framework for comparisons with other spiralians and lay the groundwork for
      investigation of the molecular mechanisms of endomesoderm formation, germ line
      segregation and bilateral differentiation in Crepidula.

PMID- 22992255
TI  - SNP calling by sequencing pooled samples.
AB  - BACKGROUND: Performing high throughput sequencing on samples pooled from
      different individuals is a strategy to characterize genetic variability at a
      small fraction of the cost required for individual sequencing. In certain
      circumstances some variability estimators have even lower variance than those
      obtained with individual sequencing. SNP calling and estimating the frequency of
      the minor allele from pooled samples, though, is a subtle exercise for at least
      three reasons. First, sequencing errors may have a much larger relevance than in
      individual SNP calling: while their impact in individual sequencing can be
      reduced by setting a restriction on a minimum number of reads per allele, this
      would have a strong and undesired effect in pools because it is unlikely that
      alleles at low frequency in the pool will be read many times. Second, the prior
      allele frequency for heterozygous sites in individuals is usually 0.5 (assuming
      one is not analyzing sequences coming from, e.g. cancer tissues), but this is not
      true in pools: in fact, under the standard neutral model, singletons (i.e.
      alleles of minimum frequency) are the most common class of variants because P(f)
      ? 1/f and they occur more often as the sample size increases. Third, an allele
      appearing only once in the reads from a pool does not necessarily correspond to a
      singleton in the set of individuals making up the pool, and vice versa, there can
      be more than one read - or, more likely, none - from a true singleton. RESULTS:
      To improve upon existing theory and software packages, we have developed a
      Bayesian approach for minor allele frequency (MAF) computation and SNP calling in
      pools (and implemented it in a program called snape): the approach takes into
      account sequencing errors and allows users to choose different priors. We also
      set up a pipeline which can simulate the coalescence process giving rise to the
      SNPs, the pooling procedure and the sequencing. We used it to compare the
      performance of snape to that of other packages. CONCLUSIONS: We present a
      software which helps in calling SNPs in pooled samples: it has good power while
      retaining a low false discovery rate (FDR). The method also provides the
      posterior probability that a SNP is segregating and the full posterior
      distribution of f for every SNP. In order to test the behaviour of our software,
      we generated (through simulated coalescence) artificial genomes and computed the
      effect of a pooled sequencing protocol, followed by SNP calling. In this setting,
      snape has better power and False Discovery Rate (FDR) than the comparable
      packages samtools, PoPoolation, Varscan : for N = 50 chromosomes, snape has power
      ~ 35%and FDR ~ 2.5%. snape is available at http://code.google.com/p/snape-pooled/
      (source code and precompiled binaries).

PMID- 22992256
TI  - Asymmetry: when is enough enough?

PMID- 22992257
TI  - List equivalency of the AzBio sentence test in noise for listeners with normal
      hearing sensitivity or cochlear implants.
AB  - BACKGROUND: Speech recognition abilities of adults and children using cochlear
      implants (CIs) are significantly degraded in the presence of background noise,
      making this an important area of study and assessment by CI manufacturers,
      researchers, and audiologists. However, at this time there are a limited number
      of fixed-intensity sentence recognition tests available that also have multiple,
      equally intelligible lists in noise. One measure of speech recognition, the AzBio
      Sentence Test, provides 10-talker babble on the commercially available compact
      disc; however, there is no published evidence to support equivalency of the 15
      sentence lists in noise for listeners with normal hearing (NH) or CIs.
      Furthermore, there is limited or no published data on the reliability, validity,
      and normative data for this test in noise for listeners with CIs or NH. PURPOSE:
      The primary goals of this study were to examine the equivalency of the AzBio
      Sentence Test lists at two signal-to-noise ratios (SNRs) in participants with NH
      and at one SNR for participants with CIs. Analyses were also conducted to
      establish the reliability, validity, and preliminary normative data for the AzBio
      Sentence Test for listeners with NH and CIs. RESEARCH DESIGN: A cross-sectional,
      repeated measures design was used to assess speech recognition in noise for
      participants with NH or CIs. STUDY SAMPLE: The sample included 14 adults with NH
      and 12 adults or adolescents with Cochlear Freedom CI sound processors.
      Participants were recruited from the University of North Texas clinic population
      or from local CI centers. DATA COLLECTION AND ANALYSIS: Speech recognition was
      assessed using the 15 lists of the AzBio Sentence Test and the 10-talker babble.
      With the intensity of the sentences fixed at 73 dB SPL, listeners with NH were
      tested at 0 and -3 dB SNRs, and participants with CIs were tested at a +10 dB
      SNR. Repeated measures analysis of variance (ANOVA) was used to analyze the data.
      RESULTS: The primary analyses revealed significant differences in performance
      across the 15 lists on the AzBio Sentence Test for listeners with NH and CIs.
      However, a follow-up analysis revealed no significant differences in performance
      across 10 of the 15 lists. Using the 10, equally-intelligible lists, a comparison
      of speech recognition performance across the two groups suggested similar
      performance between NH participants at a -3 dB SNR and the CI users at a +10 SNR.
      Several additional analyses were conducted to support the reliability and
      validity of the 10 equally intelligible AzBio sentence lists in noise, and
      preliminary normative data were provided. CONCLUSIONS: Ten lists of the
      commercial version of the AzBio Sentence Test may be used as a reliable and valid
      measure of speech recognition in noise in listeners with NH or CIs. The
      equivalent lists may be used for a variety of purposes including audiological
      evaluations, determination of CI candidacy, hearing aid and CI programming
      considerations, research, and recommendations for hearing assistive technology.
      In addition, the preliminary normative data provided in this study establishes a
      starting point for the creation of comprehensive normative data for the AzBio
      Sentence Test.

PMID- 22992258
TI  - Development and validation of a cisplatin dose-ototoxicity model.
AB  - BACKGROUND: Cisplatin is effective in the treatment of several cancers but is a
      known ototoxin resulting in shifts to hearing sensitivity in up to 50-60% of
      patients. Cisplatin-induced hearing shifts tend to occur first within an octave
      of a patient's high frequency hearing limit, termed the sensitive range for
      ototoxicity (SRO), and progress to lower frequencies. While it is currently not
      possible to know which patients will experience ototoxicity without testing their
      hearing directly, monitoring the SRO provides an early indication of damage. A
      tool to help forecast susceptibility to ototoxic-induced changes in the SRO in
      advance of each chemotherapy treatment visit may prove useful for ototoxicity
      monitoring efforts, patient counseling, and therapeutic planning. PURPOSE: This
      project was designed to (1) establish pretreatment risk curves that quantify the
      probability that a new patient will suffer hearing loss within the SRO during
      treatment with cisplatin and (2) evaluate the accuracy of these predictions in an
      independent sample of Veterans receiving cisplatin for the treatment of cancer.
      STUDY SAMPLE: Two study samples were used. The Developmental sample contained 23
      subjects while the Validation sample consisted of 12 subjects. DATA COLLECTION
      AND ANALYSIS: Risk curve predictions for SRO threshold shifts following cisplatin
      exposure were developed using a Developmental sample comprised of data from a
      total of 155 treatment visits obtained in 45 ears of 23 Veterans. Pure-tone
      thresholds were obtained within each subject's SRO at each treatment visit and
      compared with baseline measures. The risk of incurring an SRO shift was
      statistically modeled as a function of factors related to chemotherapy treatment
      (cisplatin dose, radiation treatment, doublet medication) and patient status
      (age, pre-exposure hearing, cancer location and stage). The model was reduced so
      that only statistically significant variables were included. Receiver-operating
      characteristic (ROC) curve analyses were then used to determine the accuracy of
      the risk curve predictions in an independent Validation sample of observations
      from over 62 treatment visits obtained in 24 ears of 12 Veterans. RESULTS: Only
      cumulative cisplatin dose and pre-exposure hearing were found to be significantly
      related to the risk for hearing shift. The dose-ototoxicity risk curve
      predictions developed from the Developmental sample yielded area under the ROC
      curve accuracy estimates of 0.85 when applied to an independent Validation
      sample. CONCLUSIONS: Cumulative cisplatin dose in combination with pre-exposure
      hearing provides an indication of whether hearing will shift in the SRO in
      advance of cisplatin administration. The validated dose-ototoxicity risk curves
      described herein can be used before and during treatment to anticipate hearing
      loss. While having such a tool would not replace serial hearing testing, it would
      be of great benefit to an ototoxicity monitoring program. It would promote
      relevant pretreatment counseling. Furthermore, for those found to be at risk of
      SRO shifts within the speech frequencies, the oncology treatment plan could
      incorporate anticipated dosing adjustments that could stave off the impact that
      ototoxicity might bring.

PMID- 22992259
TI  - The effects of energetic and informational masking on The Words-in-Noise Test
      (WIN).
AB  - BACKGROUND: In certain masking paradigms, the masker can have two components,
      energetic and informational. Energetic masking is the traditional peripheral
      masking, whereas informational masking involves confusions (uncertainty) between
      the signal and masker that originate more centrally in the auditory system.
      Sperry et al (1997) used Northwestern University Auditory Test No. 6 (NU-6) words
      in multitalker babble to study the differential effects of energetic and
      informational masking using babble played temporally forward (FB) and backward
      (BB). The FB and BB are the same except BB is void of the contextual and semantic
      content cues that are available in FB. It is these informational cues that are
      thought to fuel informational masking. Sperry et al found 15% better recognition
      performance (~3 dB) on BB than on FB, which can be interpreted as the presence of
      informational masking in the FB condition and not in the BB condition (Dirks and
      Bower, 1969). The Words-in-Noise Test (WIN) (Wilson, 2003; Wilson and McArdle,
      2007) uses NU-6 words as the signal and multitalker babble as the masker, which
      is a combination of stimuli that potentially could produce informational masking.
      The WIN presents 5 or 10 words at each of seven signal-to-noise ratios (S/N, SNR)
      from 24 to 0 dB in 4 dB decrements with the 50% correct point being the metric of
      interest. The same recordings of the NU-6 words and multitalker babble used by
      Sperry et al are used in the WIN. PURPOSE: To determine whether informational
      masking was involved with the WIN. RESEARCH DESIGN: Descriptive, quasi
      experimental designs were conducted in three experiments using FB and BB in
      various paradigms in which FB and BB varied from 4.3 sec concatenated segments to
      essentially continuous. STUDY SAMPLE: Eighty young adults with normal hearing and
      64 older adults with sensorineural hearing losses participated in a series of
      three experiments. DATA COLLECTION AND ANALYSIS: Experiment 1 compared
      performance on the normal WIN (FB) with performance on the WIN in which the
      babble segment with each word was reversed temporally (BB). Experiment 2 examined
      the effects of continuous FB and BB segments on WIN performance. Experiment 3
      replicated the Sperry et al (1997) experiment at 4 and 0 dB S/N using NU-6 words
      in the FB and BB conditions. RESULTS: Experiment 1-with the WIN paradigm,
      recognition performances on FB and BB were the same for listeners with normal
      hearing and listeners with hearing loss, except at the 0 dB S/N with the
      listeners with normal hearing at which performance was significantly better on BB
      than FB. Experiment 2-recognition performances on FB and BB were the same at all
      SNRs for listeners with normal hearing using a slightly modified WIN paradigm.
      Experiment 3-there was no difference in performances on the FB and BB conditions
      with either of the two SNRs. CONCLUSIONS: Informational masking was not involved
      in the WIN paradigm. The Sperry et al results were not replicated, which is
      thought to be related to the way in which the Sperry et al BB condition was
      produced.

PMID- 22992260
TI  - Intertester reliability of the acceptable noise level.
AB  - BACKGROUND: The acceptable noise level (ANL) serves to accurately predict the
      listener's likelihood of success with amplification. It has been proposed as a
      pre-hearing aid fitting protocol for hearing aid selection and counseling
      purposes. The ANL is a subjective measure of the listener's ability to accept
      background noise. Measurement of ANL relies on the tester and listener to follow
      the instructions set forth. To date, no research has explored the reliability of
      ANL as measured across clinicians or testers. PURPOSE: To examine the intertester
      reliability of ANL. RESEARCH DESIGN: A descriptive quasi-experimental reliability
      study was completed. ANL was measured for one group of listeners by three
      testers. STUDY SAMPLE: Three participants served as testers. Each tester was
      familiar with basic audiometry. Twenty-five young adults with normal hearing
      served as listeners. DATA COLLECTION/ANALYSIS: Each tester was stationed in a
      laboratory with the needed equipment. Listeners were instructed to report to
      these laboratories in a random order provided by the experimenters. The testers
      assessed most comfortable listening level (MCL) and background noise level (BNL)
      for all 25 listeners. RESULTS: Intraclass correlation coefficients were
      significant and revealed that MCL, BNL, and ANLs are reliable across testers.
      Additionally, one-way ANOVAs for MCL, BNL, and ANL were not significant. These
      findings indicate that MCL, BNL, and ANL do not differ significantly when
      measured by different testers. CONCLUSIONS: If the ANL instruction set is
      accurately followed, ANL can be reliably measured across testers, laboratories,
      and clinics. Intertester reliability of ANL allows for comparison across ANLs
      measured by different individuals. Findings of the present study indicate that
      tester reliability can be ruled out as a factor contributing to the disparity of
      mean ANLs reported in the literature.

PMID- 22992261
TI  - Acceptance of background noise, working memory capacity, and auditory evoked
      potentials in subjects with normal hearing.
AB  - BACKGROUND: The acceptable noise level (ANL) test is a method for quantifying the
      amount of background noise that subjects accept when listening to speech. Large
      variations in ANL have been seen between normal-hearing subjects and between
      studies of normal-hearing subjects, but few explanatory variables have been
      identified. PURPOSE: To explore a possible relationship between a Swedish version
      of the ANL test, working memory capacity (WMC), and auditory evoked potentials
      (AEPs). RESEARCH DESIGN: ANL, WMC, and AEP were tested in a counterbalanced order
      across subjects. STUDY SAMPLE: Twenty-one normal-hearing subjects participated in
      the study (14 females and 7 males; aged 20-39 yr with an average of 25.7 yr).
      DATA COLLECTION AND ANALYSIS: Reported data consists of age, pure-tone average
      (PTA), most comfortable level (MCL), background noise level (BNL), ANL (i.e., MCL
      - BNL), AEP latencies, AEP amplitudes, and WMC. Spearman's rank correlation
      coefficient was calculated between the collected variables to investigate
      associations. A principal component analysis (PCA) with Varimax rotation was
      conducted on the collected variables to explore underlying factors and estimate
      interactions between the tested variables. Subjects were also pooled into two
      groups depending on their results on the WMC test, one group with a score lower
      than the average and one with a score higher than the average. Comparisons
      between these two groups were made using the Mann-Whitney U-test with Bonferroni
      correction for multiple comparisons. RESULTS: A negative association was found
      between ANL and WMC but not between AEP and ANL or WMC. Furthermore, ANL is
      derived from MCL and BNL, and a significant positive association was found
      between BNL and WMC. However, no significant associations were seen between AEP
      latencies and amplitudes and the demographic variables, MCL, and BNL. The PCA
      identified two underlying factors: One that contained MCL, BNL, ANL, and WMC and
      another that contained latency for wave Na and amplitudes for waves V and Na-Pa.
      Using the variables in the first factor, the findings were further explored by
      pooling the subjects into two groups according to their WMC (WMClow and WMChigh).
      It was found that the WMClow had significantly poorer BNL than the WMChigh.
      CONCLUSIONS: The findings suggest that there is a strong relationship between BNL
      and WMC, while the association between MCL, ANL, and WMC seems less clear-cut.

PMID- 22992262
TI  - Pure-tone hearing asymmetry: a logistic approach modeling age, sex, and noise
      exposure history.
AB  - BACKGROUND: Asymmetric hearing loss (AHL) can be an early sign of vestibular
      schwannoma (VS). However, recognizing VS-induced AHL is challenging. There is no
      universally accepted definition of a "medically significant pure-tone hearing
      asymmetry," in part because AHL is a common feature of medically benign forms of
      hearing loss (e.g., age- or firearm-related hearing loss). In most cases, the
      determination that an observed AHL does not come from a benign cause involves
      subjective clinical judgment. PURPOSE: Our purpose was threefold: (1) to quantify
      hearing asymmetry distributions in a large group of patients with medically
      benign forms of hearing loss, stratifying for age, sex, and noise exposure
      history; (2) to assess how previously proposed hearing asymmetry calculations
      segregate tumor from nontumor cases; and (3) to present the results of a logistic
      regression method for defining hearing asymmetry that incorporates age, sex, and
      noise information. RESEARCH DESIGN: Retrospective chart review. STUDY SAMPLE:
      Five thousand six hundred and sixty-one patients with idiopathic, age- or noise
      exposure-related hearing loss and 85 untreated VS patients. DATA COLLECTION AND
      ANALYSIS: Audiometric, patient history, and clinical impression data were
      collected from 22,785 consecutive patient visits to the audiology section at Mayo
      Clinic in Florida from 2006 to 2009 to screen for eligibility. Those eligible
      were then stratified by VS presence, age, sex, and self-reported noise exposure
      history. Pure-tone asymmetry distributions were analyzed. Audiometric data from
      VS diagnoses were used to create four additional audiograms per patient to model
      the hypothetical development of AHL prior to the actual hearing test. The ability
      of 11 previously defined hearing asymmetry calculations to distinguish between VS
      and non-VS cases was described. A logistic regression model was developed that
      integrated age, sex, and noise exposure history with pure-tone asymmetry data.
      Regression model performance was then compared to existing asymmetry calculation
      methods. RESULTS: The 11 existing pure-tone asymmetry calculations varied in
      tumor detection performance. Age, sex, and noise exposure history helped to
      predict benign forms of hearing asymmetry. The logistic regression model
      outperformed existing asymmetry calculations and better accounted for normal age
      , sex-, and noise exposure-related asymmetry variability. CONCLUSIONS: Our
      logistic regression asymmetry method improves the clinician's ability to estimate
      risk of VS, in part by integrating categorical patient history and numeric test
      data. This form of modeling can enhance clinical decision making in audiology and
      otology.

PMID- 22992263
TI  - Safety and preliminary results of perioperative chemotherapy and hyperthermic
      intraperitoneal chemotherapy (HIPEC) for high-risk gastric cancer patients.
AB  - BACKGROUND: Gastric cancer relapse occurs in about 30% of the patients treated
      with gastrectomy and D2-lymphadenectomy, mainly as distant or peritoneal
      metastases. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated
      with an improvement in survival and lower peritoneal recurrence, albeit with
      increased morbidity. The aim of this study is to report the preliminary results
      of the association of perioperative chemotherapy, radical surgery and HIPEC in
      high-risk gastric patients in a single institution. METHODS: Treatment protocol
      was started in 2007 and included patients younger than 65 years old, with good
      performance status and gastric adenocarcinoma with serosa involvement and lymph
      node metastases, located in the body or antrum. Patients should receive three
      preoperative cycles of DCF (Docetaxel 75 mg/m2, Cisplatin 75 mg/m2 and continuous
      intravenous infusion of 5-Fluorouracil 750 mg/m2 for 5 days), followed by gastric
      resection with D2-lymphadenectomy, hyperthermic intraperitoneal chemotherapy with
      Mytomicin C 34 mg/m2 and three more postoperative cycles of DCF. RESULTS: Ten
      patients were included between 2007 and 2011. Their median age was 47 years old
      and six were male. Nine were staged with cT4 cN + tumors and one as cT3 cN+. Nine
      patients completed all three preoperative chemotherapy cycles. Eight individuals
      were treated with a total gastrectomy and the other two had a distal gastrectomy,
      all having HIPEC. Postoperative morbidity was 50%, with no deaths. Regarding
      postoperative chemotherapy, only 5 patients completed three cycles. With a median
      follow-up of 25 months, three relapses were identified and 7 patients remain
      disease-free, two with more than 4 years of follow-up. CONCLUSION: The
      association of perioperative systemic and intraperitoneal chemotherapy plus
      radical surgery is a feasible multimodality treatment, with acceptable morbidity.
      With a longer follow-up and a larger group of patients, we hope to be able to
      determine if it also influences survival outcomes and patterns of recurrence.
      MINI-ABSTRACT: The association of perioperative chemotherapy, gastric resection
      and D2-lymphadenectomy and hyperthermic intraperitoneal chemotherapy proved to be
      associated with acceptable morbidity. For survival analysis, a longer follow-up
      is needed.

PMID- 22992264
TI  - Entomopathogenic fungi, Metarhizium anisopliae and Beauveria bassiana reduce the
      survival of Xenopsylla brasiliensis larvae (Siphonaptera: Pulicidae).
AB  - BACKGROUND: Entomopathogenic fungi, particularly those belonging to the genera
      Metarhizium and Beauveria have shown great promise as arthropod vector control
      tools. These agents, however, have not been evaluated against flea vectors of
      plague. FINDINGS: A 3-h exposure to the fungi coated paper at a concentration of
      2 * 108 conidia m-2 infected >90% of flea larvae cadavers in the treatment
      groups. The infection reduced the survival of larvae that had been exposed to
      fungus relative to controls. The daily risk of dying was four- and over three
      fold greater in larvae exposed to M. anisopliae (HR = 4, p<0.001) and B. bassiana
      (HR = 3.5, p<0.001) respectively. Both fungi can successfully infect and kill
      larvae of X. brasiliensis with a pooled median survival time (MST+/-SE) of 2 +/-
      0.31 days post-exposure. CONCLUSION: These findings justify further research to
      investigate the bio-control potential of entomopathogenic fungi against fleas.

PMID- 22992266
TI  - Atrial fibrillation following cardiac surgery: risk analysis and long-term
      survival.
AB  - BACKGROUND: We studied potential risk factors for postoperative atrial
      fibrillation (POAF) in a large cohort of patients who underwent open-heart
      surgery, evaluating short- and long-term outcome, and we developed a risk
      assessment model of POAF. METHODS: A retrospective study of 744 patients without
      prior history of AF who underwent CABG (n = 513), OPCAB (n = 207), and/or AVR (n
      = 156) at Landspitali Hospital in 2002-2006. Logistic regression analysis was
      used to study risk factors for POAF, comparing patients with and without POAF.
      RESULTS: The rate of POAF was 44%, and was higher following AVR (74%) than after
      CABG (44%) or OPCAB (35%). In general, patients with POAF were significantly
      older, were more often female, were less likely to be smokers, had a lower EF,
      and had a higher EuroSCORE. The use of antiarrythmics was similar in the groups
      but patients who experienced POAF were less likely to be taking statins. POAF
      patients also had longer hospital stay, higher rates of complications, and
      operative mortality (5% vs. 0.7%). In multivariate analysis, AVR (OR 4.4), a
      preoperative history of cardiac failure (OR 1.8), higher EuroSCORE (OR 1.1), and
      advanced age (OR 1.1) were independent prognostic factors for POAF. Overall five
      year survival was 83% and 93% for patients with and without POAF (p <0.001).
      CONCLUSION: POAF was detected in 44% of patients, which is high compared to other
      studies. In the future, our assessment score will hopefully be of use in
      identifying patients at high risk of POAF and lower complications related to
      POAF.

PMID- 22992265
TI  - Identification of novel candidate genes for follicle selection in the broiler
      breeder ovary.
AB  - BACKGROUND: Broiler breeders fed ad libitum are characterised by multiple
      ovulation, which leads to poor shell quality and egg production. Multiple
      ovulation is controlled by food restriction in commercial flocks. However, the
      level of food restriction raises welfare concerns, including that of severe
      hunger. Reducing the rate of multiple ovulation by genetic selection would
      facilitate progress towards developing a growth profile for optimum animal
      welfare. RESULTS: The study utilised 3 models of ovarian follicle development;
      laying hens fed ad libitum (experiment 2) and broiler breeders fed ad libitum or
      a restricted diet (experiments 1 & 3). This allowed us to investigate gene
      candidates for follicular development by comparing normal, abnormal and
      "controlled" follicle hierarchies at different stages of development. Several
      candidate genes for multiple ovulation were identified by combining microarray
      analysis of restricted vs. ad libitum feeding, literature searches and QPCR
      expression profiling throughout follicle development. Three candidate genes were
      confirmed by QPCR as showing significant differential expression between
      restricted and ad libitum feeding: FSHR, GDF9 and PDGFRL. PDGFRL, a candidate for
      steroidogenesis, showed significantly up-regulated expression in 6-8 mm follicles
      of ad libitum fed broiler breeders (P = 0.016), the period at which follicle
      recruitment occurs. CONCLUSIONS: Gene candidates have been identified and
      evidence provided to support a possible role in regulation of ovarian function
      and follicle number. Further characterisation of these genes will be required to
      assess their potential for inclusion into breeding programmes to improve the
      regulation of follicle selection and reduce the need for feed restriction.

PMID- 22992268
TI  - Regio- and enantioselective palladium-catalyzed allylic alkylation of
      nitromethane with monosubstituted allyl substrates: synthesis of (R)-rolipram and
      (R)-baclofen.
AB  - The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane
      with monosubstituted allyl substrates was realized for the first time to provide
      corresponding products in high yields with excellent regio- and
      enantioselectivities. The protocol was applied to the enantioselective synthesis
      of (R)-baclofen and (R)-rolipram.

PMID- 22992267
TI  - Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a
      double-blind randomized controlled trial.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most commonly occurring
      neoplasms and a leading cause of cancer death worldwide, and new preventive
      strategies are needed to lower the burden of this disease. Eicosapentaenoic acid
      (EPA), the omega-3 polyunsaturated fatty acid that is widely used in the
      treatment of hyperlipidemia and prevention of cardiovascular disease, has
      recently been suggested to have a suppressive effect on tumorigenesis and cancer
      cell growth. In CRC chemoprevention trials, in general, the incidence of polyps
      or of the cancer itself is set as the study endpoint. Although the incidence rate
      of CRC would be the most reliable endpoint, use of this endpoint would be
      unsuitable for chemoprevention trials, because of the relatively low occurrence
      rate of CRC in the general population and the long-term observation period that
      it would necessitate. Moreover, there is an ethical problem in conducting long
      term trials to determine whether a test drug might be effective or harmful.
      Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger
      in diameter and stain more darkly with methylene blue than normal crypts, are
      considered as a reliable surrogate biomarker of CRC. Thus, we devised a
      prospective randomized controlled trial as a preliminary study prior to a CRC
      chemoprevention trial to evaluate the chemopreventive effect of EPA against
      colorectal ACF formation and the safety of this drug, in patients scheduled for
      polypectomy. METHODS: This study is a multicenter, double-blind, placebo
      controlled, randomized controlled trial to be conducted in patients with both
      colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients
      shall be recruited for the study and the number of ACF in the rectum counted at
      the baseline colonoscopy. Then, the participants shall be allocated randomly to
      either one of two groups, the EPA group and the placebo group. Patients in the
      EPA group shall receive oral 900-mg EPA capsules thrice daily (total daily dose,
      2.7 g per day), and those in the placebo group shall receive oral placebo
      capsules thrice daily. After one month's treatment with EPA/placebo, colonoscopic
      examination and polypectomy will be performed to evaluate the formation of ACF,
      and the cell-proliferative activity and cell-apoptotic activity in normal
      colorectal mucosa and colorectal polyps. DISCUSSION: This is the first study
      proposed to explore the effect of EPA against colorectal ACF formation in
      humans.This trial has been registered in the University hospital Medical
      Information Network (UMIN) Clinical Trials Registry as UMIN000008172.

PMID- 22992269
TI  - From incus bypass to malleostapedotomy: technical improvements and results.
AB  - OBJECTIVE: To assess results of malleostapedotomy using a Fisch Storz titanium
      piston with at least 10 months' follow up. METHODS: Using a prospective database,
      the indications, surgical technique, and pre- and post-operative audiometric data
      for 60 patients undergoing malleostapedotomy between 2002 and 2010 were
      evaluated. Diagnoses and primary and revision surgeries were compared with
      reference to the literature. RESULTS: Sixty endaural malleostapedotomies were
      performed, 28 as a primary intervention and 32 as revision surgery. In 68 per
      cent, the underlying pathology was otosclerosis. The most common reason for
      revision surgery (i.e. in 59 per cent) was prosthesis dysfunction. Overall, the
      mean air-bone gap (0.5-3 kHz) for the primary intervention and revision surgery
      groups was 9.4 and 11.3 dB, respectively; an air-bone gap of less than 20 dB was
      obtained in 100 and 81 per cent of patients, respectively. There was no
      significant audiological difference between the primary and revision surgeries
      groups, and no deafness. CONCLUSION: Malleostapedotomy shows comparable results
      to standard incus-stapedotomy and may be preferable in the presented situations.

PMID- 22992270
TI  - Endoscopic, endonasal, trans-sphenoidal hypophysectomy: retrospective analysis of
      171 procedures.
AB  - INTRODUCTION: Endoscopic, transnasal management of pituitary gland neoplasms is a
      widely accepted alternative to the traditional microscopic approach. This study
      aimed to determine outcomes and complication rates for the largest UK series of
      endoscopic, trans-sphenoidal hypophysectomies reported to date. METHODS: We
      performed a retrospective analysis of 136 primary resections and 35 revision
      cases performed at a tertiary referral centre. RESULTS AND ANALYSIS: Total tumour
      resection was confirmed in over 85 per cent of primary and revision cases, with
      biochemical remission in 60 per cent. The incidence of complications such as
      epistaxis, sphenoid sinus problems, endocrine insufficiency, visual disturbance,
      post-operative haemorrhage, cranial nerve injury and mortality was significantly
      lower, compared with similar series using the microscopic approach. CONCLUSION:
      Despite its steep 'learning curve', our series demonstrates that the endoscopic
      approach not only allows superior anatomical visualisation and therefore
      facilitates full oncological resection of tumours, but also reduces the incidence
      of peri-operative complications.

PMID- 22992271
TI  - Six years of evidence-based adult dissection tonsillectomy with ultrasonic
      scalpel, bipolar electrocautery, bipolar radiofrequency or 'cold steel'
      dissection.
AB  - OBJECTIVE: To conduct an adequately powered, prospective, randomised, controlled
      trial comparing adult dissection tonsillectomy using either ultrasonic scalpel,
      bipolar electrocautery, bipolar radiofrequency or 'cold steel' dissection.
      METHODS: Three hundred patients were randomised into four tonsillectomy technique
      groups. The operative time, intra-operative bleeding, post-operative pain,
      tonsillar fossa healing, return to full diet, return to work and post-operative
      complications were recorded. RESULTS: The bipolar radiofrequency group had a
      shorter mean operative time. The mean intra-operative blood loss during bipolar
      radiofrequency tonsillectomy was significantly less compared with cold dissection
      and ultrasonic scalpel tonsillectomy. Pain scores were significantly higher after
      bipolar electrocautery tonsillectomy. Patients undergoing bipolar electrocautery
      tonsillectomy required significantly more days to return to full diet and work.
      The bipolar electrocautery group showed significantly reduced tonsillar fossa
      healing during the first and second post-operative weeks. CONCLUSION: In this
      adult series, bipolar radiofrequency tonsillectomy was superior to ultrasonic,
      bipolar electrocautery and cold dissection tonsillectomies. This method combines
      the advantages of 'hot' and 'cold' tonsillectomy.

PMID- 22992272
TI  - Glomangiopericytoma (sinonasal-type haemangiopericytoma).
AB  - BACKGROUND: Glomangiopericytoma is a rare sinonasal tumour of perivascular myoid
      phenotype, which accounts for less than 1 per cent of all sinonasal tumours.
      OBJECTIVE: Discussion of the clinical presentation, histopathological features
      and advances in the management of sinonasal and skull base glomangiopericytoma.
      CASE REPORT: A 32-year-old woman presented with worsening nasal obstruction,
      anosmia, severe frontal headaches and right-sided proptosis. Radiographic and
      endoscopic examination revealed a right-sided, vascular mass involving the nasal
      cavity, paranasal sinuses and anterior skull base. Histopathological features
      were consistent with a glomangiopericytoma. Complete endoscopic resection with
      free margins was achieved. CONCLUSION: Glomangiopericytomas are rare, vascular,
      sinonasal tumours. Successful management depends on complete resection,
      traditionally achieved via an open approach. However, recent advances in
      endoscopic surgical approaches have enabled complete endoscopic resection of
      these tumours, minimising morbidity and facilitating subsequent surveillance of
      the operative site.

PMID- 22992274
TI  - Retraction: Colon and rectal surgery for cancer without mechanical bowel
      preparation: one-center randomized prospective trial.

PMID- 22992273
TI  - Effects of ground and joint reaction force exercise on lumbar spine and femoral
      neck bone mineral density in postmenopausal women: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Low bone mineral density (BMD) and subsequent fractures are a major
      public health problem in postmenopausal women. The purpose of this study was to
      use the aggregate data meta-analytic approach to examine the effects of ground
      (for example, walking) and/or joint reaction (for example, strength training)
      exercise on femoral neck (FN) and lumbar spine (LS) BMD in postmenopausal women.
      METHODS: The a priori inclusion criteria were: (1) randomized controlled trials,
      (2) exercise intervention >= 24 weeks, (3) comparative control group, (4)
      postmenopausal women, (5) participants not regularly active, i.e., less than 150
      minutes of moderate intensity (3.0 to 5.9 metabolic equivalents) weight bearing
      endurance activity per week, less than 75 minutes of vigorous intensity (> 6.0
      metabolic equivalents) weight bearing endurance activity per week, resistance
      training < 2 times per week, (6) published and unpublished studies in any
      language since January 1, 1989, (7) BMD data available at the FN and/or LS.
      Studies were located by searching six electronic databases, cross-referencing,
      hand searching and expert review. Dual selection of studies and data abstraction
      were performed. Hedge's standardized effect size (g) was calculated for each FN
      and LS BMD result and pooled using random-effects models. Z-score alpha values,
      95%confidence intervals (CI) and number-needed-to-treat (NNT) were calculated for
      pooled results. Heterogeneity was examined using Q and I2. Mixed-effects ANOVA
      and simple meta-regression were used to examine changes in FN and LS BMD
      according to selected categorical and continuous variables. Statistical
      significance was set at an alpha value <=0.05 and a trend at >0.05 to <= 0.10.
      RESULTS: Small, statistically significant exercise minus control group
      improvements were found for both FN (28 g's, 1632 participants, g = 0.288, 95% CI
      = 0.102, 0.474, p = 0.002, Q = 90.5, p < 0.0001, I2 = 70.1%, NNT = 6) and LS (28
      g's, 1504 participants, g = 0.179, 95% CI = -0.003, 0.361, p = 0.05, Q = 77.7, p
      < 0.0001, I2 = 65.3%, NNT = 6) BMD. Clinically, it was estimated that the overall
      changes in FN and LS would reduce the 20-year relative risk of osteoporotic
      fracture at any site by approximately 11% and 10%, respectively. None of the
      mixed-effects ANOVA analyses were statistically significant. Statistically
      significant, or a trend for statistically significant, associations were observed
      for changes in FN and LS BMD and 20 different predictors. CONCLUSIONS: The
      overall findings suggest that exercise may result in clinically relevant benefits
      to FN and LS BMD in postmenopausal women. Several of the observed associations
      appear worthy of further investigation in well-designed randomized controlled
      trials.

PMID- 22992275
TI  - Universal coverage in an era of privatisation: can we guarantee health for all?

PMID- 22992276
TI  - Postmenopausal breast cancer in Iran; risk factors and their population
      attributable fractions.
AB  - BACKGROUND: Causes of the rapidly increasing incidence of breast cancer in Middle
      East and Asian countries are incompletely understood. We evaluated risk factors
      for postmenopausal breast cancer and estimated their attributable fraction in
      Iran. METHODS: We performed a hospital-based case-control study, including 493
      women, diagnosed with breast cancer at 50 years or later between 2005-2008, and
      493 controls. We used logistic regression models to estimate multivariable odds
      ratios (OR) and 95% confidence intervals (CI), and population attributable
      fractions (PAF) for significant risk factors. RESULTS: The risk of breast cancer
      decreased with increasing parity. Compared with nulliparous women, the adjusted
      OR (95% CI) was 0.53 (0.25-1.15) for parity 1-3, 0.47 (0.29-0.93) for parity 4-6
      and 0.23 (0.11-0.50) for parity >= 7. The estimated PAF for parity (<7) was 52%.
      The positive association between body mass index (BMI) and breast cancer risk was
      confined to women diagnosed at 58 years or later. Compared with normal weight
      women (BMI 18.5-24.9), overweight (BMI 25-29.9) and obese (BMI >= 30) women were
      at increased risk of breast cancer diagnosed at 58 years or later (ORs [95% CI]
      1.27 [0.97-2.65] and 2.34 [1.33-4.14], respectively). The estimated PAF for
      obesity/overweight (BMI >25) was approximately 25%. The family history was
      significantly associated with increased breast cancer risk, but not increasing
      height, early age at menarche, late age at first birth or short breastfeeding.
      CONCLUSIONS: Decreasing parity and increasing obesity are determinants of
      increasing breast cancer incidence among Iranian women. These trends predict a
      continuing upward trend of postmenopausal breast cancer.

PMID- 22992277
TI  - Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B:
      Implications for timing of prophylactic thyroidectomy.
AB  - BACKGROUND: Patients with Multiple Endocrine Neoplasia type 2 (MEN 2) are at high
      risk of developing aggressive medullary thyroid carcinoma (MTC) in childhood,
      with the highest risk in those with MEN type 2B (of whom >95% have an M918T RET
      proto-oncogene mutation). Metastatic MTC has been reported as young as 3 months
      of age. Current guidelines recommend prophylactic thyroidectomy within the first
      year of life for MEN 2B. PATIENT FINDINGS: We report a 9-week-old infant with MTC
      due to familial MEN 2B. A full-term male infant, born to a mother with known MEN
      2B and metastatic MTC, had an M918T RET proto-oncogene mutation confirmed at 4
      weeks of age. He underwent prophylactic total thyroidectomy at 9 weeks of age.
      Pathology showed a focal calcitonin-positive nodule (2.5 mm), consistent with
      microscopic MTC. SUMMARY: This case highlights the importance of early
      prophylactic thyroidectomy in MEN 2B. Although current guidelines recommend
      surgery up to a year of life, MTC may occur in the first few weeks of life,
      raising the question of how early we should intervene. In this report, we discuss
      the risks, benefits and barriers to performing earlier thyroidectomy, soon after
      the first month of life, and make suggestions to facilitate timely intervention.
      Prenatal anticipatory surgical scheduling could be considered in familial MEN 2B.
      Multidisciplinary collaboration between adult and pediatric specialists is key to
      the optimal management of the infant at risk.

PMID- 22992278
TI  - Mining and characterization of ubiquitin E3 ligases expressed in the mouse
      testis.
AB  - BACKGROUND: Ubiquitin-mediated protein modification and degradation are believed
      to play important roles in mammalian spermatogenesis. The catalogues of ubiquitin
      activating enzymes, conjugating enzymes, and ligases (E3s) have been known for
      mammals such as mice and humans. However, a systematic characterization of E3s
      expressed during spermatogenesis has not been carried out. RESULTS: In present
      study, we set out to mine E3s from the mouse genome and to characterize their
      expression pattern, subcellular localization, and enzymatic activities based on
      microarray data and biochemical assays. We identified 398 putative E3s belonging
      to the RING, U-box, and HECT subfamilies and found that most genes were conserved
      between mice and humans. We discovered that 73 of them were highly or
      specifically expressed in the testes based on the microarray expression data. We
      selected 10 putative E3 genes to examine their mRNA expression pattern, and
      several genes to study their subcellular localization and E3 ligase activity. RT
      PCR results showed that all the selected genes were predominately expressed in
      the testis. Some putative E3s were localized in the cytoplasm while others were
      in both the cytoplasm and the nucleus. Moreover, all the selected proteins were
      enzymatically active as demonstrated by in vitro and in vivo assays. CONCLUSIONS:
      We have identified a large number of putative E3s that are expressed during mouse
      spermatogenesis. Among these, a significant portion is highly or specifically
      expressed in the testis. Subcellular localization and enzymatic activity assays
      suggested that these E3s might execute diverse functions in mammalian
      spermatogenesis. Our results may serve as an initial guide to the field for
      further functional analysis.

PMID- 22992279
TI  - Residents' corner September 2012. sQUIZ your knowledge! Borrelial lymphocytoma.

PMID- 22992280
TI  - Prospective validation of the "rhino conjunctivitis allergy-control-SCORE(c)" (RC
      ACS(c)).
AB  - BACKGROUND: Recently we reported the validation of the "Allergy-Control-SCORE(c)
      (ACS)" which assesses symptom severity as well as medication use on three
      dimensions lung, nose and eyes. The aim of this study was to test the validity of
      the score for eyes and nose. METHODS: One-hundred-twenty-one consenting subjects
      (age 19-65y), including 81 patients with allergic rhino-conjunctivitis (RC) and
      40 healthy controls, participated in the study. Patients rated daily nasal and
      eye symptoms using a 4-point scale (none, mild, moderate, and severe) and their
      use of anti-symptomatic medication. Validation criteria were pollen counts in the
      course of the study period. Discrimination capacity was analyzed by comparing the
      rhino-conjunctivitis Allergy-Control-SCORE(c) (RC-ACS(c)) values of allergic
      patients and healthy controls. Convergent reliability was assessed by correlating
      RC-ACS(c) values with the global severity of allergy, the quality of life, and
      the allergy-related medical consultations. Retest reliability was assessed by the
      correlation of the repeated measured RC-ACS(c) scores during each of two
      consecutive weeks. RESULTS: Convergent reliability analysis indicated a
      significant correlation between RC-Allergy-Control-SCORE(c) and global severity
      of allergy (r = 0.691; p < 0.0001), quality of life (r = 0.757; p < 0.0001) and
      allergy-related medical consultations (r = 0.329; p = 0.0019). RC-Allergy-Control
      SCORE(c) showed a good retest reliability (r = 0.813; p < 0.001) and
      discriminated extremely well between allergic patients and healthy controls
      (Median: 3.7 range: 0; 14.1 vs. Median: 0 range: 0; 2.9; p < 0.001), with a
      sensitivity of 93.8% and a specificity of 92.5% at a score value of 0.786.
      CONCLUSIONS: The RC-ACS(c) can be considered as valid and reliable to assess the
      severity of rhino-conjunctivitis severity in clinical trials and observational
      studies.

PMID- 22992281
TI  - First report of Toxoplasma gondii seroprevalence in peafowls in Yunnan Province,
      Southwestern China.
AB  - BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite infecting
      almost all warm-blooded animals, including birds, with a worldwide distribution.
      Surveys of T. gondii infection in wild birds have been reported extensively in
      the world, but little is known of T. gondii infection in peafowls worldwide. This
      study was performed to determine the seroprevalence of T. gondii infection in
      peafowls in Yunnan Province, southwestern China. METHODS: Sera from 277 peafowls,
      including 272 blue peafowls (Pavo cristatus) and 5 green peafowls (Pavo muticus)
      originated from two geographic areas in Yunnan Province were assayed for T.
      gondii antibodies using the modified agglutination test (MAT). RESULTS: Specific
      T. gondii antibodies were detected in 35 of 277 (12.64%) peafowls (MAT titer >=
      1:5). Seropositive birds were found in both species, 33 in 272 blue peafowls and
      2 in 5 green peafowls. There was no significant difference in T. gondii
      seroprevalence between the adolescent birds (6.74%) and the adult birds (6.67%)
      (P > 0.05). The geographical origins of peafowls was found to be highly
      associated with T. gondii infection in the present study, a statistically
      significant difference in T. gondii seropositivity was observed between peafowls
      from Kunming (31.08%) and those from Xishuangbanna Dai Autonomous Prefecture
      (5.91%) (OR = 10.956, 95% CI = 1.632-73.545, P = 0.014). Statistical analyses
      showed that there were no significant interactions between ages and geographical
      origins of peafowls (P > 0.05). CONCLUSIONS: The results of the present survey
      indicated that infection of peafowls with T. gondii is widespread in Yunnan
      Province, which has significant public health concerns and implications for
      prevention and control of toxoplamosis in this province. To our knowledge, this
      is the first seroprevalence report of T. gondii infection in China's southwestern
      Yunnan Province.

PMID- 22992282
TI  - Steam-cooking rapidly destroys and reverses onion-induced antiplatelet activity.
AB  - BACKGROUND: Foods in the diet that can aid in the prevention of diseases are of
      major interest. Onions are key ingredients in many cuisines around the world and
      moreover, onion demand has trended higher over the past three decades. An
      important pharmacological aspect of onion is the ability to inhibit platelet
      aggregation. Raw onions inhibit platelet aggregation; however, when onions are
      boiled or heated, antiplatelet activity may be abolished. METHODS: Onion quarters
      were steamed for 0, 1, 3, 6, 10, and 15 min. The in vitro antiplatelet activity
      of a yellow hybrid storage onion was examined at these times on the blood of 12
      human subjects using in vitro whole blood aggregometry. RESULTS: Contrary to
      findings reported for boiling, antiplatelet activity was destroyed between 3 and
      6 min of steaming, and at 10 min of steaming, cooked onions stimulated platelet
      activity. Extracts from cooked onion had the potential to reverse the inhibitory
      effect on blood platelets by 25%. Responses were consistent across all donors.
      Total polyphenolic concentration and soluble solids were not affected by steaming
      time. CONCLUSIONS: The potential value of cooked onion preparations may result in
      destruction or reversal of antiplatelet activity, without affecting the
      polyphenolic concentration.

PMID- 22992284
TI  - A history of HbA1c through Clinical Chemistry and Laboratory Medicine.
AB  - HbA(1c) was discovered in the late 1960s and its use as marker of glycemic
      control has gradually increased over the course of the last four decades.
      Recognized as the gold standard of diabetic survey, this parameter was
      successfully implemented in clinical practice in the 1970s and 1980s and
      internationally standardized in the 1990s and 2000s. The use of standardized and
      well-controlled methods, with well-defined performance criteria, has recently
      opened new directions for HbA(1c) use in patient care, e.g., for diabetes
      diagnosis. Many reports devoted to HbA1c have been published in Clinical
      Chemistry and Laboratory Medicine (CCLM) journal. This review reminds the major
      steps of HbA(1c) history, with a special emphasis on the contribution of CCLM in
      this field.

PMID- 22992283
TI  - IkappaBalpha deficiency in brain leads to elevated basal neuroinflammation and
      attenuated response following traumatic brain injury: implications for functional
      recovery.
AB  - BACKGROUND: The transcription factor NFkappaB is an important mediator of cell
      survival and inflammation in the immune system. In the central nervous system
      (CNS), NFkappaB signaling has been implicated in regulating neuronal survival
      following acute pathologic damage such as traumatic brain injury (TBI) and
      stroke. NFkappaB is normally bound by the principal inhibitory protein,
      IkappaBalpha, and sequestered in the cytoplasm. Activation of NFkappaB requires
      the degradation of IkappaBalpha, thereby freeing NFkappaB to translocate to the
      nucleus and activate the target genes. Mice deficient in IkappaBalpha display
      deregulated and sustained NFkappaB activation and early postnatal lethality,
      highlighting a critical role of IkappaBalpha in NFkappaB regulation. RESULTS: We
      investigated the role of IkappaBalpha in regulating NFkappaB activity in the
      brain and the effects of the NFkappaB/IkappaBalpha pathway in mediating
      neuroinflammation under both physiological and brain injury conditions. We report
      that astrocytes, but not neurons, exhibit prominent NFkappaB activity, and that
      basal NFkappaB activity in astrocytes is elevated in the absence of IkappaBalpha.
      By generating mice with brain-specific deletion of IkappaBalpha, we show that
      IkappaBalpha deficiency does not compromise normal brain development. However,
      basal neuroinflammation detected by GFAP and Iba1 immunoreactivity is elevated.
      This leads to impaired inflammatory responses following TBI and worsened brain
      damage including higher blood brain barrier permeability, increased injury
      volumes and enlarged ventricle volumes. CONCLUSIONS: We conclude that, in the
      CNS, astrocyte is the primary cell type subject to NFkappaB regulation. We
      further demonstrate that IkappaBalpha plays an important role in regulating
      NFkappaB activity in the brain and a robust NFkappaB/IkappaBalpha-mediated
      neuroinflammatory response immediately following TBI is beneficial.

PMID- 22992285
TI  - Circulating matrix Gla protein: a potential tool to  identify minor carotid
      stenosis with calcification  in a risk population.
AB  - BACKGROUND: Carotid calcification is an independent marker for future ischemic
      events, which are more frequently encountered in postmenopausal women as the
      prevalence of type 2 diabetes mellitus (T2DM) and hypertension (HT) increases.
      Matrix Gla protein (MGP) is a major inhibitor of vascular calcification. Here, we
      report on the prospect of serum MGP to become an identifying tool for minor
      carotid stenosis (minCAS) with calcification in a risk population. METHODS: Based
      on carotid ultrasound examination, out of 72 enrolled postmenopausal women, 33
      had minCAS with carotid calcification (minCAS group) and 39 were without minCAS
      and carotid calcification (non-minCAS group). Serum total MGP, high-sensitivity C
      reactive protein (hs-CRP), bone mineral density (BMD) and carotid intima-media
      thickness (CIMT) were determined. RESULTS: We found significantly elevated serum
      MGP levels in the minCAS compared to the non-minCAS group (p < 0.05). MGP was
      independently associated with hs-CRP (unstandardized beta -regression coefficient
      = 2.6; 95 % CI 0.007 - 5.3; p = 0.049) and CIMT ( beta = - 611.3; 95 % CI -
      1172.6 - - 49.9; p = 0.034) within the minCAS group, but not with BMD.
      Furthermore, significantly higher MGP levels were determined in two minCAS
      subgroups (one with HT or T2DM and second with both diseases) compared to a non
      minCAS subgroup with HT or T2DM (p < 0.05 and p < 0.01, respectively). A
      threshold of 87.9 MU g/L serum MGP (area under the receiver operating
      characteristic = 0.72 } 0.06; 95 % CI 0.60 - 0.84; p = 0.001) may identify minCAS
      with calcification in postmenopausal women with 63 % precision. CONCLUSIONS:
      Higher circulating MGP levels could help identify minCAS with calcification in a
      relatively homogenous risk population (i.e., postmenopausal women), regardless of
      underlying cardiovascular risk factors.

PMID- 22992286
TI  - The emerging role of biomarkers and bio-impedance in evaluating hydration status
      in patients with acute heart failure.
AB  - The quantitative and qualitative estimation of total body fluid content has
      proven to be crucial for both diagnosis and prognosis assessment in patients with
      heart failure. The aim of this review is to summarize the current techniques for
      assessing body hydration status as well as the principal biomarkers associated
      with acute heart failure (AHF). Although clinical history, physical examination
      and classical imaging techniques(e.g., standard radiography and
      echocardiography)still represent the cornerstones, novel and promising tools,such
      as biomarkers and bio-electrical impedance are achieving an emerging role in
      clinical practice for the assessment of total body fluid content. In the acute
      setting, the leading advantages of these innovative methods over device are
      represented by the much lower invasiveness and the reasonable costs, coupled with
      an easier and faster application. This article is mainly focused on AHF patients,
      not only because the overall prevalence of this disease is dramatically
      increasing worldwide, but also because it is well-known that their fluid overload
      has a remarkable diagnostic and prognostic significance. It is thereby
      conceivable that the bio-electrical vector analysis (BIVA) coupled with
      laboratory biomarkers might achieve much success in AHF patient management in the
      future, especially for assisting diagnosis, risk stratification,and therapeutic
      decision-making.

PMID- 22992287
TI  - Development and testing of the Norwegian version of the Clinical Learning
      Environment, Supervision and Nurse Teacher (CLES+T) evaluation scale.
AB  - Several instruments have been developed to monitor nursing students' subjective
      evaluation of clinical placement. The Clinical Learning Environment, Supervision
      and Nurse Teacher (CLES+T) evaluation scale measures five dimensions. The purpose
      of this study was to translate and test the construct validity and internal
      consistency of the evaluation scale within a Norwegian context. The questionnaire
      was distributed to all students in four university colleges (n=1229) in 2009 with
      a response rate of 41.6 % (n=511). Only students from institutional practice
      settings (n=407) were included in the analysis. The instrument has properties
      suitable for evaluation also within a Norwegian context, despite some minor
      differences in factor structure, indicating common underlying properties
      regarding students' evaluation of the clinical learning environment and how they
      rate the premises of nursing on the ward.

PMID- 22992288
TI  - Bayesian inference for a  nonlinear mixed-effects Tobit model with multivariate
      skew-t distributions: application to AIDS studies.
AB  - Censored data are characteristics of many bioassays in HIV/AIDS studies where
      assays may not be sensitive enough to determine gradations in viral load
      determination among those below a detectable threshold. Not accounting for such
      left-censoring appropriately can lead to biased parameter estimates in most data
      analysis. To properly adjust for left-censoring, this paper presents an extension
      of the Tobit model for fitting nonlinear dynamic mixed-effects models with skew
      distributions. Such extensions allow one to specify the conditional distributions
      for viral load response to account for left-censoring, skewness and heaviness in
      the tails of the distributions of the response variable. A Bayesian modeling
      approach via Markov Chain Monte Carlo (MCMC) algorithm is used to estimate model
      parameters. The proposed methods are illustrated using real data from an HIV/AIDS
      study.

PMID- 22992289
TI  - A general implementation of TMLE for longitudinal data applied to causal
      inference in survival analysis.
AB  - In many randomized controlled trials the outcome of interest is a time to event,
      and one measures on each subject baseline covariates and time-dependent
      covariates until the subject either drops-out, the time to event is observed, or
      the end of study is reached. The goal of such a study is to assess the causal
      effect of the treatment on the survival curve. We present a targeted maximum
      likelihood estimator of the causal effect of treatment on survival fully
      utilizing all the available covariate information, resulting in a double robust
      locally efficient substitution estimator that will be consistent and
      asymptotically linear if either the censoring mechanism is consistently
      estimated, or if the maximum likelihood based estimator is already consistent. In
      particular, under the independent censoring assumption assumed by current
      methods, this TMLE is always consistent and asymptotically linear so that it
      provides valid confidence intervals and tests. Furthermore, we show that when
      both the censoring mechanism and the initial maximum likelihood based estimator
      are mis-specified, and thus inconsistent, the TMLE exhibits stability when
      inverse probability weighted estimators and double robust estimating equation
      based methods break down The TMLE is used to analyze the Tshepo study, a study
      designed to evaluate the efficacy, tolerability, and development of drug
      resistance of six different first-line antiretroviral therapies. Most importantly
      this paper presents a general algorithm that may be used to create targeted
      maximum likelihood estimators of a large class of parameters of interest for
      general longitudinal data structures.

PMID- 22992290
TI  - Next generation sequencing and comparative analyses of Xenopus mitogenomes.
AB  - BACKGROUND: Mitochondrial genomes comprise a small but critical component of the
      total DNA in eukaryotic organisms. They encode several key proteins for the
      cell's major energy producing apparatus, the mitochondrial respiratory chain.
      Additionally, their nucleotide and amino acid sequences are of great utility as
      markers for systematics, molecular ecology and forensics. Their characterization
      through nucleotide sequencing is a fundamental starting point in mitogenomics.
      Methods to amplify complete mitochondrial genomes rapidly and efficiently from
      microgram quantities of tissue of single individuals are, however, not always
      available. Here we validate two approaches, which combine long-PCR with Roche 454
      pyrosequencing technology, to obtain two complete mitochondrial genomes from
      individual amphibian species. RESULTS: We obtained two new xenopus frogs (Xenopus
      borealis and X. victorianus) complete mitochondrial genome sequences by means of
      long-PCR followed by 454 of individual genomes (approach 1) or of multiple pooled
      genomes (approach 2), the mean depth of coverage per nucleotide was 9823 and 186,
      respectively. We also characterised and compared the new mitogenomes against
      their sister taxa; X. laevis and Silurana tropicalis, two of the most intensely
      studied amphibians. Our results demonstrate how our approaches can be used to
      obtain complete amphibian mitogenomes with depths of coverage that far surpass
      traditional primer-walking strategies, at either the same cost or less. Our
      results also demonstrate: that the size, gene content and order are the same
      among xenopus mitogenomes and that S. tropicalis form a separate clade to the
      other xenopus, among which X. laevis and X. victorianus were most closely
      related. Nucleotide and amino acid diversity was found to vary across the xenopus
      mitogenomes, with the greatest diversity observed in the Complex 1 gene nad4l and
      the least diversity observed in Complex 4 genes (cox1-3). All protein-coding
      genes were shown to be under strong negative (purifying selection), with genes
      under the strongest pressure (Complex 4) also being the most highly expressed,
      highlighting their potentially crucial functions in the mitochondrial respiratory
      chain. CONCLUSIONS: Next generation sequencing of long-PCR amplicons using single
      taxon or multi-taxon approaches enabled two new species of Xenopus mtDNA to be
      fully characterized. We anticipate our complete mitochondrial genome
      amplification methods to be applicable to other amphibians, helpful for
      identifying the most appropriate markers for differentiating species, populations
      and resolving phylogenies, a pressing need since amphibians are undergoing
      drastic global decline. Our mtDNAs also provide templates for conserved primer
      design and the assembly of RNA and DNA reads following high throughput "omic"
      techniques such as RNA- and ChIP-seq. These could help us better understand how
      processes such mitochondrial replication and gene expression influence xenopus
      growth and development, as well as how they evolved and are regulated.

PMID- 22992291
TI  - Arthritis education: the integration of patient-reported outcome measures and
      patient self-management.
AB  - OBJECTIVES: To assess the integration of PROMs and patient education, using the
      joint-fitness programme, and the effectiveness of this combined approach on
      disease activity and adherence to therapy. METHODS: This was a double-blind
      randomised controlled study which included 147 arthritic patients monitored over
      18 months. Every patient completed a PROMs questionnaire. By the 6th month of
      treatment, the patients were randomly allocated to an active group (74 patients)
      that was able to view former self-reported PROMs scores and discuss the
      implementation of the joint fitness programme as a tool for psycho-educational
      interventions. The control group (73 patients) continued their treatment and
      management based on viewing their recorded PROMs and clinical assessment. The
      patients were assessed at 3 monthly intervals for another 12 months. The primary
      outcome was the change in the patients' adherence to their medications, disease
      activity score (DAS-28) and PROMs domains. RESULTS: The integration of patient
      education and PROMs led to a significant greater reduction of disease activity
      parameters, DAS-28 score, as well as improvement of the patients' adherence to
      therapy (p<0.01). The improvement of disease activity parameters was associated
      with the improvement in functional disability and quality of life scores. At 18
      month-follow-up, both the self-management and cognitive behavioural therapy
      intervention demonstrated improvement for disease activity (effect size 1.4 and
      1.2 respectively). CONCLUSIONS: The integration of patient education and PROMs
      succeeded in improving self-perceived health as well as disease activity. The
      patient education for patients with inflammatory arthritis is feasible in the
      standard clinical practice.

PMID- 22992292
TI  - Policy initiation and political levers in health policy: lessons from Ghana's
      health insurance.
AB  - BACKGROUND: Understanding the health policy formulation process over the years
      has focused on the content of policy to the neglect of context. This had led to
      several policy initiatives having a still birth or ineffective policy choices
      with sub-optimal outcomes when implemented. Sometimes, the difficulty has been
      finding congruence between different values and interests of the various
      stakeholders. How can policy initiators leverage the various subtle mechanisms
      that various players draw on to leverage their interests during policy
      formulation. This paper attempts to conceptualise these levers of policy
      formulation to enhance an understanding of this field of work based on lived
      experience. METHODOLOGY: This is a qualitative participant observation case study
      based on retrospective recollection of the policy process and political levers
      involved in developing the Ghana National Health Insurance Scheme. The study uses
      a four-concept framework which is agenda setting, symbols manipulation,
      constituency preservation and coalition building to capture the various issues,
      negotiations and nuanced approaches used in arriving at desired outcomes.
      RESULTS: Technical experts, civil society, academicians and politicians all had
      significant influence on setting the health insurance agenda. Each of these
      various stakeholders carefully engaged in ways that preserved their constituency
      interests through explicit manoeuvres and subtle engagements. Where proposals
      lend themselves to various interpretations, stakeholders were quick to latch on
      the contentious issues to preserve their constituency and will manipulate the
      symbols that arise from the proposals to their advantage. Where interests are
      contested and the price of losing out will leave government worse off which will
      favour its political opponent, it will push for divergent interests outside
      parliamentary politics through intense negotiations to build coalitions so a
      particular policy may pass. CONCLUSIONS: This paper has examined the policy
      environment and the political leverages in retrospect at arriving at Ghana's
      health insurance policy and design. New perspectives have been brought to the
      dynamics of the interactions of the 3 streams of problem, policy and politics. It
      provides lessons which suggest that in understanding the policy process, it is
      important that actors engage with the content as well as the context to
      understand viewpoints that may be expressed by interest groups. This will empower
      policy proponents to achieve easier results and limit the frustrations associated
      with the policy process. There are no straight and determined pathways for
      achieving outcomes so appreciating the evidence and basis for design, negotiation
      process and building coalitions along the way are skills to be mastered.

PMID- 22992293
TI  - Astragalus saponins downregulate vascular endothelial growth factor under cobalt
      chloride-stimulated hypoxia in colon cancer cells.
AB  - BACKGROUND: Our ongoing research has revealed that total saponins extracted from
      the medicinal herb Radix Astragali (AST) exhibits significant growth-inhibitory
      and proapoptotic effects in human cancer cells. In the present study, the
      potential of AST in controlling angiogenesis was further investigated with
      elaboration of the underlying molecular mechanism in human colon cancer cell and
      tumor xenograft. RESULTS: AST decreased the protein level of VEGF and bFGF in HCT
      116 colon cancer cells in a time- and dose-dependent manner. Among the Akt/mTOR
      signal transduction molecules being examined, AST caused PTEN upregulation,
      reduction in Akt phosphorylation and subsequent activation of mTOR. AST also
      suppressed the induction of HIF-1alpha and VEGF under CoCl2-mimicked hypoxia.
      These effects were intensified by combined treatment of AST with the mTOR
      inhibitor rapamycin. Despite this, our data also indicate that AST could
      attenuate cobalt chloride-evoked COX-2 activation, while such effect on COX-2 and
      its downstream target VEGF was intensified when indomethacin was concurrently
      treated. The anti-carcinogenic action of AST was further illustrated in HCT 116
      xenografted athymic nude mice. AST significantly suppressed tumor growth and
      reduced serum VEGF level in vivo. In the tumor tissues excised from AST-treated
      animals, protein level of p-Akt, p-mTOR, VEGF, VEGFR1 and VEGFR2 was down
      regulated. Immunohistochemistry has also revealed that AST effectively reduced
      the level of COX-2 in tumor sections when compared with that in untreated
      control. CONCLUSION: Taken together, these findings suggest that AST exerts anti
      carcinogenic activity in colon cancer cells through modulation of mTOR signaling
      and downregulation of COX-2, which together reduce VEGF level in tumor cells that
      could potentially suppress angiogenesis.

PMID- 22992294
TI  - Development of a 3D finite element model of lens microcirculation.
AB  - BACKGROUND: It has been proposed that in the absence of a blood supply, the
      ocular lens operates an internal microcirculation system. This system delivers
      nutrients, removes waste products and maintains ionic homeostasis in the lens.
      The microcirculation is generated by spatial differences in membrane transport
      properties; and previously has been modelled by an equivalent electrical circuit
      and solved analytically. While effective, this approach did not fully account for
      all the anatomical and functional complexities of the lens. To encapsulate these
      complexities we have created a 3D finite element computer model of the lens.
      METHODS: Initially, we created an anatomically-correct representative mesh of the
      lens. We then implemented the Stokes and advective Nernst-Plank equations, in
      order to model the water and ion fluxes respectively. Next we complemented the
      model with experimentally-measured surface ionic concentrations as boundary
      conditions and solved it. RESULTS: Our model calculated the standing ionic
      concentrations and electrical potential gradients in the lens. Furthermore, it
      generated vector maps of intra- and extracellular space ion and water fluxes that
      are proposed to circulate throughout the lens. These fields have only been
      measured on the surface of the lens and our calculations are the first 3D
      representation of their direction and magnitude in the lens. CONCLUSION: Values
      for steady state standing fields for concentration and electrical potential plus
      ionic and fluid fluxes calculated by our model exhibited broad agreement with
      observed experimental values. Our model of lens function represents a platform to
      integrate new experimental data as they emerge and assist us to understand how
      the integrated structure and function of the lens contributes to the maintenance
      of its transparency.

PMID- 22992295
TI  - Acute ischemic stroke following Hump-nosed viper envenoming; first authenticated
      case.
AB  - Hump-nosed pit viper (Genus Hypnale) is a medically important venomous snake in
      Sri Lanka and Southwestern India which causes significant morbidity and
      mortality. Envenoming of this snake results in hemostastic dysfunction,
      thrombotic microangiopathy, acute kidney injury and death. This case describes an
      authenticated first case of ischemic stroke in a 65 year old male following
      envenoming by H.hypnale in Sri Lanka.

PMID- 22992297
TI  - Putative filariosis outbreak in white and black rhinoceros at Meru National Park
      in Kenya.
AB  - BACKGROUND: Habitat and food supply loss and disruption, together with man's
      pursuit of the animal's unique horn pose significant threats to the charismatic
      rhinoceros. Filarial worms have been thought to cause cutaneous lesions in black
      rhinoceros (Diceros bicornis) in Kenya and South Africa, but never in white
      rhinoceros (Ceratotherium simum) in the wild, despite the fact that the two
      species live often in close proximity. Stephanofilaria dinniki has been
      implicated in the past as the causal agents for such lesions. FINDINGS: In this
      paper we report a putative filariosis outbreak in both black and white rhinos at
      Meru National Park in Kenya. Four black and five white rhinos were affected by
      various degrees of filarioid-like lesions, while apparently all sympatric wild
      and domestic animals were filarial worm-free. Affected rhinos were captured and
      successfully treated. Comparison between the epidemiological aspects of white and
      black rhinoceros filariosis, and the possible relations between this outbreak and
      annual seasons, the presence of oxpeckers and other host species are discussed.
      CONCLUSIONS: Our study highlights (i) that filarial infection is not restricted
      to black rhinos, but it affects both rhinoceros species, and (ii) the importance
      of the earlier detection and immediate treatment (capture-treat and release) of
      filarioid infections, which is of pivotal interest for wildlife conservation, and
      especially the endangered and isolated white and black rhinoceros populations.

PMID- 22992296
TI  - Enhancing tobacco quitline effectiveness: identifying a superior pharmacotherapy
      adjuvant.
AB  - INTRODUCTION: Telephone tobacco quitlines are effective and are widely used, with
      more than 500,000 U.S. callers in 2010. This study investigated the clinical
      effectiveness and cost-effectiveness of 3 different quitline enhancements:
      combination nicotine replacement therapy (NRT), longer duration of NRT, and
      counseling to increase NRT adherence. METHODS: In this study, 987 quitline
      callers were randomized to a combination of quitline treatments in a 2 * 2 * 2
      factorial design: NRT duration (2 vs. 6 weeks), NRT type (nicotine patch only vs.
      patch plus nicotine gum), and standard 4-call counseling (SC) versus SC plus
      medication adherence counseling (MAC). The primary outcome was 7-day point
      prevalence abstinence (PPA) at 6 months postquit in intention-to-treat (ITT)
      analyses. RESULTS: Combination NRT for 6 weeks yielded the highest 6-month PPA
      rate (51.6%) compared with 2 weeks of nicotine patch (38.4%), odds ratios [OR] =
      1.71 (95% confidence interval [CI]:1.20-2.45). A similar result was found for 2
      weeks of combination NRT (48.2%), OR = 1.49 (95% CI: 1.04-2.14) but not for 6
      weeks of nicotine patch alone (46.2%), OR = 1.38 (95% CI: 0.96-1.97). The MAC
      intervention effect was nonsignificant. Cost analyses showed that the 2-week
      combination NRT group had the lowest cost per quit ($442 vs. $464 for 2-week
      patch only, $505 for 6-week patch only, and $675 for 6-week combination NRT).
      CONCLUSIONS: Combination NRT for 2 or 6 weeks increased 6-month abstinence rates
      by 10% and 13%, respectively, over rates produced by 2 weeks of nicotine patch
      when offered with quitline counseling. A 10% improvement would potentially yield
      an additional 50,000 quitters annually, assuming 500,000 callers to U.S.
      quitlines per year.

PMID- 22992298
TI  - "What's wrong with grandma?": depictions of Alzheimer's disease in children's
      storybooks.
AB  - Alzheimer's disease (AD) affects the entire family system, including young
      children. Yet there are few resources to help children understand AD. Storybooks
      are used to educate children about other diseases and may be useful in AD as
      well. In this study, we examined the depiction of AD in 33 English-language
      children's storybooks written specifically about AD. As a group, storybooks
      present AD as a brain disease, but provide little information about the
      diagnostic process or treatments. Clinical presentations are diverse among
      characters with AD, and no single book presents a comprehensive depiction of the
      cognitive, behavioral, affective, and functional symptoms of the disease. In
      fact, the prevalence of some symptoms in this "population" of storybook
      characters diverges substantially from epidemiological reports. Books designed to
      familiarize children about AD should be comprehensive and accurate. Current
      resources, while useful, could be improved to ensure health literacy about AD in
      young children.

PMID- 22992299
TI  - Cognitive profile of the earliest stage of dementia in Parkinson's disease.
AB  - Recently, a strong interest has emerged in recognizing Parkinson's disease
      dementia (PDD) at a very early stage. However, the specific profile of the
      earliest stages of PDD is still unclear and a matter of considerable controversy.
      The objective of this study was to find out early neuropsychological markers for
      progression of dementia in this population. Fifty-eight patients with PDD were
      divided into 2 subgroups on the basis of the Mini-Mental State Examination: very
      mild and mild. The comparison with 26 normal controls shows that very mild PDD
      had deficits on attention/executive functions, naming,
      visuospatial/constructional abilities and retrieval of the episodic memory.
      Patients with mild PDD showed additional deficits on coding of episodic memory.
      Moreover, we found that in this early stage of PDD, the progression of dementia
      is mainly related to deterioration of attention/executive functions as well as
      retrieval and coding of episodic memory.

PMID- 22992300
TI  - Post-infective transverse myelitis following Streptococcus pneumoniae meningitis
      with radiological features of acute disseminated encephalomyelitis: a case
      report.
AB  - INTRODUCTION: Post-infectious autoimmune demyelination of the central nervous
      system is a rare neurological disorder typically associated with exanthematous
      viral infections. We report an unusual presentation of the condition and a
      previously undocumented association with Streptococcus pneumonia meningitis. CASE
      PRESENTATION: A 50-year-old Caucasian woman presented to our facility with an
      acute myelopathy three days after discharge following acute Streptococcus
      pneumoniae meningitis. Imaging studies of the spine ruled out an infective focus
      and no other lesions were seen within the cord. Diffuse, bilateral white matter
      lesions were seen within the cerebral hemispheres, and our patient was diagnosed
      as having a post-infective demyelination syndrome that met the diagnostic
      criteria for an acute transverse myelitis. Our patient clinically and
      radiologically improved following treatment with steroids. CONCLUSIONS: The novel
      association of a Streptococcus pneumoniae infection with post-infectious
      autoimmune central nervous system demyelination should alert the reader to the
      potentially causative role of this common organism, and gives insights into the
      pathogenesis. The unusual dissociation between the clinical presentation and the
      location of the radiological lesions should also highlight the potential for the
      condition to mimic the presentation of others, and stimulates debate on the
      definitions of acute transverse myelitis and acute disseminated
      encephalomyelitis, and their potential overlap.

PMID- 22992302
TI  - Dysfunctional breathing phenotype in adults with asthma - incidence and risk
      factors.
AB  - BACKGROUND: Abnormal breathing patterns may cause characteristic symptoms and
      impair quality of life. In a cross-sectional survey 29% of adults treated for
      asthma in primary care had symptoms suggestive of dysfunctional breathing (DB),
      more likely to be female and younger, with no differences for severity of asthma.
      No clear risk factors were demonstrated for DB in asthma, nor the impact of
      asthma medication was evaluated. The objective of this study was to describe the
      DB phenotype in adults with asthma treated in a specialised asthma centre.
      METHODS: Adult patients aged 17-65 with diagnosed asthma were screened for DB
      using the Nijmegen questionnaire (positive predictive score >23) and confirmed by
      progressive exercise testing. The following were evaluated as independent risk
      factors for DB in the multiple regression analysis: female sex; atopy, obesity,
      active smoker, moderate/severe rhinitis, psychopathology, GERD, arterial
      hypertension; severe asthma, asthma duration > 5 years, lack of asthma control,
      fixed airway obstruction, fast lung function decline, frequent exacerbator and
      brittle asthma phenotypes; lack of ICS, use of LABA or LTRA. RESULTS: 91 adults
      with asthma, mean age 35.04 +/-1.19 years, 47(51.65%) females were evaluated. 27
      (29.67%) subjects had a positive screening score on Nijmegen questionnaire and
      16(17.58%) were confirmed by progressive exercise testing as having DB.
      Independent risk factors for DB were psychopathology (p = 0.000002), frequent
      exacerbator asthma phenotype (p = 0.01) and uncontrolled asthma (p < 0.000001).
      CONCLUSION: Dysfunctional breathing is not infrequent in asthma patients and
      should be evaluated in asthma patients presenting with psychopathology, frequent
      severe asthma exacerbations or uncontrolled asthma. Asthma medication (ICS, LABA
      or LTRA) had no significant relation with dysfunctional breathing.

PMID- 22992301
TI  - Small interfering RNA-mediated suppression of Ccl2 in Muller cells attenuates
      microglial recruitment and photoreceptor death following retinal degeneration.
AB  - BACKGROUND: The recruitment and activation of inflammatory cells is thought to
      exacerbate photoreceptor death in retinal degenerative conditions such as age
      related macular degeneration (AMD). We investigated the role of Muller cell
      derived chemokine (C-C motif) ligand (Ccl)2 expression on monocyte/microglia
      infiltration and photoreceptor death in light-mediated retinal degeneration,
      using targeted small interfering (si)RNA. METHODS: Adult Sprague-Dawley rats were
      injected intravitreally with 1 MUg of either Ccl2 siRNA or scrambled siRNA, and
      were then exposed to 1000 lux of light for a period of 24 hours. The mice were
      given an overdose of barbiturate, and the retinas harvested and evaluated for the
      effects of bright-light exposure. Ccl2 expression was assessed by quantitative
      PCR, immunohistochemistry, and in situ hybridization. Monocytes/microglia were
      counted on retinal cryostat sections immunolabeled with the markers ED1 and
      ionized calcium binding adaptor (IBA)1, and photoreceptor apoptosis was assessed
      using terminal dUTP nick end labeling. RESULTS: Intravitreal injection of Ccl2
      siRNA significantly reduced the expression of Ccl2 following light damage to 29%
      compared with controls. In retinas injected with Ccl2 siRNA, in situ
      hybridization and immunohistochemistry on retinal cryostat sections showed a
      substantial decrease in Ccl2 within Muller cells. Cell counts showed
      significantly fewer ED1-positive and IBA1-positive cells in the retinal
      vasculature and outer nuclear layer of Ccl2 siRNA-injected retinas, compared with
      controls. Moreover, there was significantly less photoreceptor apoptosis in Ccl2
      siRNA-injected retinas compared with controls. CONCLUSIONS: Our data indicate
      that Ccl2 expression by Muller cells promotes the infiltration of
      monocytes/microglia, thereby contributing to the neuroinflammatory response and
      photoreceptor death following retinal injury. Modulation of exaggerated chemokine
      responses using siRNA may have value in reducing inflammation-mediated cell death
      in retinal degenerative disease such as AMD.

PMID- 22992303
TI  - Design and rationale of FOCUS (PX-171-011): a randomized, open-label, phase 3
      study of carfilzomib versus best supportive care regimen in patients with
      relapsed and refractory multiple myeloma (R/R MM).
AB  - BACKGROUND: Carfilzomib is a next-generation proteasome inhibitor with single
      agent activity in patients with relapsed and refractory multiple myeloma (R/R
      MM). In PX-171-003-A1, a single-arm phase 2 study of carfilzomib monotherapy in
      heavily pretreated patients, the overall response rate was 23.7%, 37% of patients
      achieved >= minimal response and median overall survival (OS) was 15.6 months.
      Based on this study, carfilzomib was recently approved by the US Food and Drug
      Administration for the treatment of R/R MM. Herein we describe the trial design
      and rationale for a phase 3 randomized study, FOCUS (CarFilzOmib for AdvanCed
      Refractory MUltiple Myeloma European Study), being conducted to compare OS after
      treatment with single-agent carfilzomib to best supportive care (BSC) regimen in
      R/R MM. METHODS: Patients must have received >=3 prior regimens, must be
      responsive to at least 1 line of therapy, and be refractory to their most recent
      therapy. Eligible patients are randomized 1:1 to receive either carfilzomib (28
      day cycles at 20 mg/m(2) IV on Days 1-2 of Cycle 1, escalating to 27 mg/m(2) IV
      on Days 8, 9, 15, and 16 and continuing at 27 mg/m(2) through Cycle 9 and Days 1,
      2, 15, and 16 >= Cycle 10) or an active BSC regimen (corticosteroid treatment of
      prednisolone 30 mg, dexamethasone 6 mg, or equivalent every other day with
      optional cyclophosphamide 50 mg PO once daily). Patients will continue treatment
      until disease progression, unacceptable toxicity, or treatment discontinuation
      and will then enter long-term follow-up for survival. The primary endpoint is OS
      and secondary endpoints include progression-free survival, overall response rate,
      and safety. Disease assessments will be determined according to the International
      Myeloma Working Group Uniform Response Criteria with minimal response per
      European Blood and Marrow Transplantation Group criteria. CONCLUSIONS: This phase
      3 trial will provide more rigorous data for carfilzomib, as this is the first
      carfilzomib study with OS as the primary endpoint and will not be confounded by
      crossover and will provide more robust secondary response and safety results that
      will add to the data set from prior phase 2 studies. FOCUS will facilitate
      regulatory approvals around the world and expand treatment options for patients
      with R/R MM. TRIAL REGISTRATION: EudraCT No. 2009-016840-38; NCT01302392.

PMID- 22992304
TI  - Cis-regulatory signatures of orthologous stress-associated bZIP transcription
      factors from rice, sorghum and Arabidopsis based on phylogenetic footprints.
AB  - BACKGROUND: The potential contribution of upstream sequence variation to the
      unique features of orthologous genes is just beginning to be unraveled. A core
      subset of stress-associated bZIP transcription factors from rice (Oryza sativa)
      formed ten clusters of orthologous groups (COG) with genes from the monocot
      sorghum (Sorghum bicolor) and dicot Arabidopsis (Arabidopsis thaliana). The total
      cis-regulatory information content of each stress-associated COG was examined by
      phylogenetic footprinting to reveal ortholog-specific, lineage-specific and
      species-specific conservation patterns. RESULTS: The most apparent pattern
      observed was the occurrence of spatially conserved 'core modules' among the COGs
      but not among paralogs. These core modules are comprised of various combinations
      of two to four putative transcription factor binding site (TFBS) classes
      associated with either developmental or stress-related functions. Outside the
      core modules are specific stress (ABA, oxidative, abiotic, biotic) or organ
      associated signals, which may be functioning as 'regulatory fine-tuners' and
      further define lineage-specific and species-specific cis-regulatory signatures.
      Orthologous monocot and dicot promoters have distinct TFBS classes involved in
      disease and oxidative-regulated expression, while the orthologous rice and
      sorghum promoters have distinct combinations of root-specific signals, a pattern
      that is not particularly conserved in Arabidopsis. CONCLUSIONS: Patterns of cis
      regulatory conservation imply that each ortholog has distinct signatures, further
      suggesting that they are potentially unique in a regulatory context despite the
      presumed conservation of broad biological function during speciation. Based on
      the observed patterns of conservation, we postulate that core modules are likely
      primary determinants of basal developmental programming, which may be integrated
      with and further elaborated by additional intrinsic or extrinsic signals in
      conjunction with lineage-specific or species-specific regulatory fine-tuners.
      This synergy may be critical for finer-scale spatio-temporal regulation, hence
      unique expression profiles of homologous transcription factors from different
      species with distinct zones of ecological adaptation such as rice, sorghum and
      Arabidopsis. The patterns revealed from these comparisons set the stage for
      further empirical validation by functional genomics.

PMID- 22992306
TI  - Residents' corner September 2012. (Carpe)DIEM. Dermatological indications for
      electron microscopy: argyria.

PMID- 22992305
TI  - The role of eight polymorphisms in three candidate genes in determining the
      susceptibility, phenotype, and response to anti-TNF therapy in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: Several single nucleotide polymorphisms (SNPs) have been associated
      with rheumatoid arthritis (RA) such as peptidylarginine deiminase-4 (PADI4),
      osteopontin (OPN), and perforin (PRF1) genes. Thus, we aimed at analysing the
      influence of eight SNPs in these candidate genes on RA susceptibility and their
      association with laboratory and clinical features in terms of response to anti
      TNF therapy. METHODS: We performed a case-control study on 377 Caucasian RA
      patients and 391 healthy, ethnicity-matched, population-based controls. All
      subjects were genotyped for PADI4_89/94, PADI4_92, PADI4_104, PADI4_100 in PADI4;
      -156G/GG and +1239A/C in OPN and A91V and N252S in PRF1 genes. The patients were
      stratified for shared epitope (SE) HLA-DRB1. rheumatoid factor (RF) and anti
      citrullinated protein/peptide antibodies (ACPA) were analysed. The patients
      started anti-TNF treatment and they were evaluated at baseline and after 12
      weeks. Disease activity was evaluated with DAS28 and response to treatment with
      EULAR criteria. RESULTS: A statistically significant association between RA and
      OPN -156G/GG was found (p=0.023). SE was firmly confirmed to be associated with
      RA (OR=3.68; p<10-10). No other statistically significant association with
      clinical and laboratory features were observed. CONCLUSIONS: For the first time,
      in an Italian cohort, we report the association between -156G/GG in OPN gene and
      RA susceptibility. Short-term response to anti-TNF therapy was not influenced by
      the genetic variants studied.

PMID- 22992307
TI  - Impact of protein pulse feeding on lean mass in malnourished and at-risk
      hospitalized elderly patients: a randomized controlled trial.
AB  - BACKGROUND & AIMS: Aging is associated with a blunted anabolic response to
      dietary intake, possibly related to a decrease in systemically available amino
      acids (AAs), which in turn may stem from increased splanchnic AA metabolism. This
      splanchnic sequestration can be saturated by pulse feeding (80% of daily protein
      intake in a single meal), enabling increased protein synthesis. This study aimed
      to evaluate the efficacy of a new nutritional strategy, termed protein pulse
      feeding. METHODS: This prospective randomized study (ClinicalTrials.gov
      registration number NCT00135590) enrolled 66 elderly malnourished or at-risk
      patients in an inpatient rehabilitation unit. All were given a controlled diet
      for 6 weeks. In a spread diet (SD) group (n = 36), dietary protein was spread
      over the four daily meals. In a pulse diet (PD) group (n = 30), 72% of dietary
      protein (1.31 g/kg weight/d on average) was consumed in one meal at noon. The
      patients were evaluated at admission and at 6 weeks for body composition [lean
      mass (LM), appendicular skeletal muscle mass (ASMM), and body cell mass (BCM)
      indices, measured by X-ray absorptiometry combined with bioelectrical impedance
      analysis] (primary outcome), hand grip strength, and activities of daily living
      (ADL) score. RESULTS: Protein pulse feeding was significantly more efficacious
      than protein spread feeding in improving LM index (mean changes from baseline for
      PD group: +0.38 kg/m(2); 95% confidence interval (CI), [0; 0.60]; for SD group: 
      0.21 kg/m(2); 95% CI, [-0.61; 0.20]; p = 0.005 between the two groups), ASMM
      index (+0.21 kg/m(2); 95% CI, [0; 0.34] and -0.11 kg/m(2); 95% CI, [-0.20; 0.09];
      p = 0.022), BCM index (+0.44 kg/m(2); 95% CI, [0.08; 0.52] and -0.04 kg/m(2); 95%
      CI, [-0.09; 0.10]; p = 0.004). There was no significant effect for hand-grip
      strength or ADL score. CONCLUSIONS: This study demonstrates for the first time
      that protein pulse feeding has a positive, clinically relevant effect on lean
      mass in malnourished and at-risk hospitalized elderly patients.

PMID- 22992308
TI  - Determinants of home parenteral nutrition dependence and survival of 268 patients
      with non-malignant short bowel syndrome.
AB  - BACKGROUND & AIMS: Short bowel syndrome (SBS) is a rare and severe condition
      where home parenteral nutrition (HPN) dependence can be either permanent or
      transient. The timing of HPN discontinuation and the survival, according to SBS
      characteristics, need to be further reported to help plan pre-emptive intestinal
      transplantation and reconstructive surgery. METHODS: 268 Non-malignant SBS
      patients have been followed in our institution since 1980. HPN dependence and
      survival rate were studied with univariate and multivariate analysis. RESULTS:
      Median follow-up was 4.4 (0.3-24) years. Actuarial HPN dependence probabilities
      were 74%, 64% and 48% at 1, 2 and 5 years, respectively. In multivariate
      analysis, HPN dependence was significantly decreased with an early (<6 mo) plasma
      citrulline concentration >20 MUmol/l, a remaining colon >57% (4/7) and a remnant
      small bowel length >75 cm. Among the 124 patients who became HPN independent,
      26.5% did so more than 2 years after SBS constitution. CONCLUSIONS: This study
      indicates that long-term HPN is required in 47% of SBS patients started on this
      therapy. HPN independence is significantly associated with the remnant small
      bowel length, remaining colon and early plasma citrulline concentration.
      Noteworthy, HPN dependence could be reversed until 5 years after SBS
      constitution.

PMID- 22992309
TI  - Efficacy of acupuncture for chronic knee pain: protocol for a randomised
      controlled trial using a Zelen design.
AB  - BACKGROUND: Chronic knee pain is a common and disabling condition in people over
      50 years of age, with knee joint osteoarthritis being a major cause. Acupuncture
      is a popular form of complementary and alternative medicine for treating pain and
      dysfunction associated with musculoskeletal conditions. This pragmatic Zelen
      design randomised controlled trial is investigating the efficacy and cost
      effectiveness of needle and laser acupuncture, administered by medical
      practitioners, in people with chronic knee pain. METHODS/DESIGN: Two hundred and
      eighty two people aged over 50 years with chronic knee pain have been recruited
      from metropolitan Melbourne and regional Victoria, Australia. Participants
      originally consented to participate in a longitudinal natural history study but
      were then covertly randomised into one of four treatment groups. One group
      continued as originally consented (ie natural history group) and received no
      acupuncture treatment. The other three were treatment groups: i) laser
      acupuncture, ii) sham laser or, iii) needle acupuncture. Acupuncture treatments
      used a combined Western and Traditional Chinese Medicine style, were delivered by
      general practitioners and comprised 8-12 visits over 12 weeks. Follow-up is
      currently ongoing. The primary outcomes are pain measured by an 11-point numeric
      rating scale (NRS) and self-reported physical function measured by the Western
      Ontario and McMaster (WOMAC) Universities Osteoarthritis Index subscale at the
      completion of treatment at 12 weeks. Secondary outcomes include quality of life,
      global rating of change scores and additional measures of pain (other NRS and
      WOMAC subscale) and physical function (NRS). Additional parameters include a
      range of psychosocial measures in order to evaluate potential relationships with
      acupuncture treatment outcomes. Relative cost-effectiveness will be determined
      from health service usage and outcome data. Follow-up assessments will also occur
      at 12 months. DISCUSSION: The findings from this study will help determine
      whether laser and/or needle acupuncture is efficacious, and cost-effective, in
      the management of chronic knee pain in older people. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry reference: ACTRN12609001001280.

PMID- 22992310
TI  - Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel
      agent CDF.
AB  - BACKGROUND: Colorectal Cancer (CRC) is one of the leading causes of death
      worldwide. Numerous cellular events, including deregulated expression of
      microRNAs (miRNAs), specifically the family of miR-34 consisting of miR-34a, b
      and c, is known to regulate the processes of growth and metastasis. METHODS: We
      evaluated the expression of miR-34 in formalin-fixed paraffin-embedded (FFPE)
      human colon cancer tissue specimens compared to normal colonic mucosa. Moreover,
      we also assessed the expression of miR-34 in colon cancer cell lines treated with
      our newly developed synthetic analogue of curcumin referred as difluorinated
      curcumin (CDF) compared to well known inhibitor of methyl transferase. RESULTS:
      We found that the expression of miR-34a and miR-34c was down-regulated in colon
      cancer specimens compared to normal colonic mucosa and the loss of expression was
      also consistent with data from colon cancer cell lines. This down-regulation was
      attributed to promoter hypermethylation, because we found that the treatment of
      colon cancer cells with 5-aza-2'-deoxycytidine, a methyltransferase inhibitor,
      markedly induced the levels of miR-34a and miR-34c expression. Likewise, CDF was
      very effective in the re-expression of miR-34a and miR-34c, which was consistent
      with inhibition of cell growth of both chemo-sensitive and chemo-resistant colon
      cancer cells. The re-expression of miR-34 led to a marked reduction in the
      expression of its target gene, Notch-1. CONCLUSION: The loss of expression of miR
      34 in colon cancer is in part due to promoter hypermethylation of miR-34, which
      can be re-expressed with our novel agent CDF, suggesting that CDF could be a
      novel demethylating agent for restoring the expression of miR-34 family, and thus
      CDF could become a newer therapeutic agent for the treatment of colon cancer.

PMID- 22992311
TI  - Health risks of climate change: an assessment of uncertainties and its
      implications for adaptation policies.
AB  - BACKGROUND: Projections of health risks of climate change are surrounded with
      uncertainties in knowledge. Understanding of these uncertainties will help the
      selection of appropriate adaptation policies. METHODS: We made an inventory of
      conceivable health impacts of climate change, explored the type and level of
      uncertainty for each impact, and discussed its implications for adaptation
      policy. A questionnaire-based expert elicitation was performed using an ordinal
      scoring scale. Experts were asked to indicate the level of precision with which
      health risks can be estimated, given the present state of knowledge. We assessed
      the individual scores, the expertise-weighted descriptive statistics, and the
      argumentation given for each score. Suggestions were made for how dealing with
      uncertainties could be taken into account in climate change adaptation policy
      strategies. RESULTS: The results showed that the direction of change could be
      indicated for most anticipated health effects. For several potential effects, too
      little knowledge exists to indicate whether any impact will occur, or whether the
      impact will be positive or negative. For several effects, rough 'order-of
      magnitude' estimates were considered possible. Factors limiting health impact
      quantification include: lack of data, multi-causality, unknown impacts
      considering a high-quality health system, complex cause-effect relations leading
      to multi-directional impacts, possible changes of present-day response-relations,
      and difficulties in predicting local climate impacts. Participants considered
      heat-related mortality and non-endemic vector-borne diseases particularly
      relevant for climate change adaptation. CONCLUSIONS: For possible climate related
      health impacts characterised by ignorance, adaptation policies that focus on
      enhancing the health system's and society's capability of dealing with possible
      future changes, uncertainties and surprises (e.g. through resilience,
      flexibility, and adaptive capacity) are most appropriate. For climate related
      health effects for which rough risk estimates are available, 'robust decision
      making' is recommended. For health effects with limited societal and policy
      relevance, we recommend focusing on no-regret measures. For highly relevant
      health effects, precautionary measures can be considered. This study indicated
      that analysing and characterising uncertainty by means of a typology can be a
      very useful approach for selection and prioritization of preferred adaptation
      policies to reduce future climate related health risks.

PMID- 22992312
TI  - Antenatal corticosteroids trial in preterm births to increase neonatal survival
      in developing countries: study protocol.
AB  - BACKGROUND: Preterm birth is a major cause of neonatal mortality, responsible for
      28% of neonatal deaths overall. The administration of antenatal corticosteroids
      to women at high risk of preterm birth is a powerful perinatal intervention to
      reduce neonatal mortality in resource rich environments. The effect of antenatal
      steroids to reduce mortality and morbidity among preterm infants in hospital
      settings in developed countries with high utilization is well established, yet
      they are not routinely used in developing countries. The impact of increasing
      antenatal steroid use in hospital or community settings with low utilization
      rates and high infant mortality among premature infants due to lack of
      specialized services has not been well researched. There is currently no clear
      evidence about the safety of antenatal corticosteroid use for community-level
      births. METHODS: We hypothesize that a multi country, two-arm, parallel cluster
      randomized controlled trial to evaluate whether a multifaceted intervention to
      increase the use of antenatal corticosteroids, including components to improve
      the identification of pregnancies at high risk of preterm birth and providing and
      facilitating the appropriate use of steroids, will reduce neonatal mortality at
      28 days of life in preterm newborns, compared with the standard delivery of care
      in selected populations of six countries. 102 clusters in Argentina, Guatemala,
      Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women
      and newborns will be enrolled. Kits containing vials of dexamethasone, syringes,
      gloves, and instructions for administration will be distributed. Improving the
      identification of women at high risk of preterm birth will be done by (1)
      diffusing recommendations for antenatal corticosteroids use to health providers,
      (2) training health providers on identification of women at high risk of preterm
      birth, (3) providing reminders to health providers on the use of the kits, and
      (4) using a color-coded tape to measure uterine height to estimate gestational
      age in women with unknown gestational age. In both intervention and control
      clusters, health providers will be trained in essential newborn care for low
      birth weight babies. The primary outcome is neonatal mortality at 28 days of life
      in preterm infants.

PMID- 22992314
TI  - Vulnerability, equity and universal coverage--a concept note.

PMID- 22992313
TI  - Delayed post-traumatic spinal cord infarction in an adult after minor head and
      neck trauma: a case report.
AB  - INTRODUCTION: Delayed post-traumatic spinal cord infarction is a devastating
      complication described in children. In adults, spinal cord ischemia after
      cardiovascular interventions, scoliosis correction, or profound hypotension has
      been reported in the literature. However, delayed spinal cord infarction after
      minor head trauma has not been described yet. CASE PRESENTATION: We report the
      case of a 45-year-old Hispanic man who had a minor head trauma. He was admitted
      to our hospital because of paresthesias in his hands and neck pain. A
      radiological workup showed cervical spinal canal stenosis and chronic cervical
      spondylotic myelopathy. Twelve hours after admission, our patient became
      unresponsive and, despite full resuscitation efforts, died. The autopsy revealed
      spinal cord necrosis involving the entire cervical spinal cord and upper thoracic
      region. CONCLUSIONS: This case illustrates the extreme fragility of spinal cord
      hemodynamics in patients with chronic cervical spinal canal stenosis, in which
      any further perturbations, such as cervical hyperflexion related to a minor head
      injury, can have catastrophic consequences. Furthermore, the delayed onset of
      spinal cord infarction in this case shows that meticulous maintenance of blood
      pressure in the acute post-traumatic period is of paramount importance, even in
      patients with minimal post-traumatic symptoms.

PMID- 22992315
TI  - Patient- and population-level health consequences of discontinuing antiretroviral
      therapy in settings with inadequate HIV treatment availability.
AB  - BACKGROUND: In resource-limited settings, HIV budgets are flattening or
      decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV
      treatment failure was modeled to highlight trade-offs among competing policy
      goals of optimizing individual and population health outcomes. METHODS: In
      settings with two available ART regimens, we assessed two strategies: (1)
      continue ART after second-line failure (Status Quo) and (2) discontinue ART after
      second-line failure (Alternative). A computer model simulated outcomes for a
      single cohort of newly detected, HIV-infected individuals. Projections were fed
      into a population-level model allowing multiple cohorts to compete for ART with
      constraints on treatment capacity. In the Alternative strategy, discontinuation
      of second-line ART occurred upon detection of antiretroviral failure, specified
      by WHO guidelines. Those discontinuing failed ART experienced an increased risk
      of AIDS-related mortality compared to those continuing ART. RESULTS: At the
      population level, the Alternative strategy increased the mean number initiating
      ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo.
      More individuals initiating ART under the Alternative strategy increased total
      life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although
      more individuals received treatment under the Alternative strategy, life
      expectancy for those treated decreased by 0.7 years (-8.0%) to 8.1 years compared
      to the Status Quo. In a cohort of treated patients only, 600 more individuals
      (+27.1%) died by 5 years under the Alternative strategy compared to the Status
      Quo. Results were sensitive to the timing of detection of ART failure, number of
      ART regimens, and treatment capacity. Although we believe the results robust in
      the short-term, this analysis reflects settings where HIV case detection occurs
      late in the disease course and treatment capacity and the incidence of newly
      detected patients are stable. CONCLUSIONS: In settings with inadequate HIV
      treatment availability, trade-offs emerge between maximizing outcomes for
      individual patients already on treatment and ensuring access to treatment for all
      people who may benefit. While individuals may derive some benefit from ART even
      after virologic failure, the aggregate public health benefit is maximized by
      providing effective therapy to the greatest number of people. These trade-offs
      should be explicit and transparent in antiretroviral policy decisions.

PMID- 22992316
TI  - The T1048I mutation in ATP7A gene causes an unusual Menkes disease presentation.
AB  - BACKGROUND: The ATP7A gene encodes the ATP7A protein, which is a trans-Golgi
      network copper transporter expressed in the brain and other organs. Mutations in
      this gene cause disorders of copper metabolism, such as Menkes disease. Here we
      describe the novel and unusual mutation (p.T1048I) in the ATP7A gene of a child
      with Menkes disease. The mutation affects a conserved DKTGT1048 phosphorylation
      motif that is involved in the catalytic activity of ATP7A. We also describe the
      clinical course and the response to copper treatment in this patient. CASE
      PRESENTATION: An 11-month-old male Caucasian infant was studied because of
      hypotonia, ataxia and global developmental delay. The patient presented low
      levels of serum copper and ceruloplasmin, and was shown to be hemizygous for the
      p.T1048I mutation in ATP7A. The diagnosis was confirmed when the patient was 18
      months old, and treatment with copper-histidinate (Cu-His) was started
      immediately. The patient showed some neurological improvement and he is currently
      8 years old. Because the p.T1048I mutation affects its catalytic site, we
      expected a complete loss of functional ATP7A and a classical Menkes disease
      presentation. However, the clinical course of the patient was mild, and he
      responded to Cu-His treatment, which suggests that this mutation leads to partial
      conservation of the activity of ATP7A. CONCLUSION: This case emphasizes the
      important correlation between genotype and phenotype in patients with Menkes
      disease. The prognosis in Menkes disease is associated with early detection,
      early initiation of treatment and with the preservation of some ATP7A activity,
      which is necessary for Cu-His treatment response. The description of this new
      mutation and the response of the patient to Cu-His treatment will contribute to
      the growing body of knowledge about treatment response in Menkes disease.

PMID- 22992317
TI  - Chronic conditions, behavioral health, and use of health services among Asian
      American men: the first nationally representative sample.
AB  - Although the Asian American population is increasing, Asian American men's health
      remains underinvestigated. This study examined the overall pattern of their
      health and health care usage. Using a nationally representative sample (N = 998)
      from the National Latino and Asian American Study (2002-2003), the first
      comprehensive epidemiological survey, rates of chronic conditions, behavioral
      health, and mental health service utilization (e.g., general medical, specialty
      mental health, and any medical services) were computed. The ages ranged from 18
      to 95 and the mean age was 41. Of the sample, there were no ethnic subgroup
      differences in most of the physical and chronic conditions, with the exception of
      allergies/hay fever, arthritis, asthma, and high blood pressure. Behavioral
      health problems and substance use varied among Asian American men with more
      Vietnamese American men reporting that they are current smokers and more Filipino
      American men reporting having ever used drugs and having higher rates of obesity.
      Levels of mental health status and health services-seeking behaviors also varied
      among Asian subgroups. Variations exist among the three subgroups of Asian
      American men with regard to chronic, behavioral, and mental health issues. The
      results provide greater understanding of the heterogeneity and relationships
      among the Asian American subgroups with respect to physical, behavioral, and
      mental health concerns. Similarities and differences in prevalence rates and use
      of health services must include examining the social context. Social factors such
      as immigration status, living environments, lifestyle, culture, and health
      insurance may help explain the variations among Asian American men.

PMID- 22992318
TI  - Habitual physical activity as a determinant of the effect of moderate physical
      exercise on postural control in older men.
AB  - The aim of the study was to compare the effect of exercise on postural control
      (PC) among the elderly with lower or higher level of habitual physical activity
      (HPA). The study involved 17 elderly men (mean age 72.9 +/- 4.79 years). Mean
      velocity of the center of pressure (COP) displacements was measured using a force
      plate both before and after cycle ergometer exercise. A significantly higher
      increase in mean velocity of COP displacements and its component in the sagittal
      plane were observed in the group with lower level of HPA in comparison with the
      group with higher HPA level. Simultaneously, a relatively similar reaction to the
      exercise in the frontal plane was observed in both groups, possibly connected to
      the specific type of used exercise, which mainly activated the sagittal muscles.

PMID- 22992320
TI  - Combinatorial control of temporal gene expression in the Drosophila wing by
      enhancers and core promoters.
AB  - BACKGROUND: The transformation of a developing epithelium into an adult structure
      is a complex process, which often involves coordinated changes in cell
      proliferation, metabolism, adhesion, and shape. To identify genetic mechanisms
      that control epithelial differentiation, we analyzed the temporal patterns of
      gene expression during metamorphosis of the Drosophila wing. RESULTS: We found
      that a striking number of genes, approximately 50% of the Drosophila
      transcriptome, exhibited changes in expression during a time course of wing
      development. While cis-acting enhancer sequences clearly correlated with these
      changes, a stronger correlation was discovered between core-promoter types and
      the dynamic patterns of gene expression within this differentiating tissue. In
      support of the hypothesis that core-promoter type influences the dynamics of
      expression, expression levels of several TATA-box binding protein associated
      factors (TAFs) and other core promoter-associated components changed during this
      developmental time course, and a testes-specific TAF (tTAF) played a critical
      role in timing cellular differentiation within the wing. CONCLUSIONS: Our results
      suggest that the combinatorial control of gene expression via cis-acting enhancer
      sequences and core-promoter types, determine the complex changes in gene
      expression that drive morphogenesis and terminal differentiation of the
      Drosophila wing epithelium.

PMID- 22992321
TI  - Transient receptor potential canonical-3 channel-dependent fibroblast regulation
      in atrial fibrillation.
AB  - BACKGROUND: Fibroblast proliferation and differentiation are central in atrial
      fibrillation (AF)-promoting remodeling. Here, we investigated fibroblast
      regulation by Ca(2+)-permeable transient receptor potential canonical-3 (TRPC3)
      channels. METHODS AND RESULTS: Freshly isolated rat cardiac fibroblasts
      abundantly expressed TRPC3 and had appreciable nonselective cation currents
      (I(NSC)) sensitive to a selective TPRC3 channel blocker, pyrazole-3 (3 MUmol/L).
      Pyrazole-3 suppressed angiotensin II-induced Ca(2+) influx, proliferation, and
      alpha-smooth muscle actin protein expression in fibroblasts. Ca(2+) removal and
      TRPC3 blockade suppressed extracellular signal-regulated kinase phosphorylation,
      and extracellular signal-regulated kinase phosphorylation inhibition reduced
      fibroblast proliferation. TRPC3 expression was upregulated in atria from AF
      patients, goats with electrically maintained AF, and dogs with tachypacing
      induced heart failure. TRPC3 knockdown (based on short hairpin RNA [shRNA])
      decreased canine atrial fibroblast proliferation. In left atrial fibroblasts
      freshly isolated from dogs kept in AF for 1 week by atrial tachypacing, TRPC3
      protein expression, currents, extracellular signal-regulated kinase
      phosphorylation, and extracellular matrix gene expression were all significantly
      increased. In cultured left atrial fibroblasts from AF dogs, proliferation rates,
      alpha-smooth muscle actin expression, and extracellular signal-regulated kinase
      phosphorylation were increased and were suppressed by pyrazole-3. MicroRNA-26 was
      downregulated in canine AF atria; experimental microRNA-26 knockdown reproduced
      AF-induced TRPC3 upregulation and fibroblast activation. MicroRNA-26 has NFAT
      (nuclear factor of activated T cells) binding sites in the 5' promoter region.
      NFAT activation increased in AF fibroblasts, and NFAT negatively regulated
      microRNA-26 transcription. In vivo pyrazole-3 administration suppressed AF while
      decreasing fibroblast proliferation and extracellular matrix gene expression.
      CONCLUSIONS: TRPC3 channels regulate cardiac fibroblast proliferation and
      differentiation, likely by controlling the Ca(2+) influx that activates
      extracellular signal-regulated kinase signaling. AF increases TRPC3 channel
      expression by causing NFAT-mediated downregulation of microRNA-26 and causes
      TRPC3-dependent enhancement of fibroblast proliferation and differentiation. In
      vivo, TRPC3 blockade prevents AF substrate development in a dog model of
      electrically maintained AF. TRPC3 likely plays an important role in AF by
      promoting fibroblast pathophysiology and is a novel potential therapeutic target.

PMID- 22992322
TI  - Dietary nitrate supplementation improves revascularization in chronic ischemia.
AB  - BACKGROUND: Revascularization is an adaptive repair mechanism that restores blood
      flow to undersupplied ischemic tissue. Nitric oxide plays an important role in
      this process. Whether dietary nitrate, serially reduced to nitrite by commensal
      bacteria in the oral cavity and subsequently to nitric oxide and other nitrogen
      oxides, enhances ischemia-induced remodeling of the vascular network is not
      known. METHODS AND RESULTS: Mice were treated with either nitrate (1 g/L sodium
      nitrate in drinking water) or sodium chloride (control) for 14 days. At day 7,
      unilateral hind-limb surgery with excision of the left femoral artery was
      conducted. Blood flow was determined by laser Doppler. Capillary density,
      myoblast apoptosis, mobilization of CD34(+)/Flk-1(+), migration of bone marrow
      derived CD31(+)/CD45(-), plasma S-nitrosothiols, nitrite, and skeletal tissue
      cGMP levels were assessed. Enhanced green fluorescence protein transgenic mice
      were used for bone marrow transplantation. Dietary nitrate increased plasma S
      nitrosothiols and nitrite, enhanced revascularization, increased mobilization of
      CD34(+)/Flk-1(+) and migration of bone marrow-derived CD31(+)/CD45(-) cells to
      the site of ischemia, and attenuated apoptosis of potentially regenerative
      myoblasts in chronically ischemic tissue. The regenerative effects of nitrate
      treatment were abolished by eradication of the nitrate-reducing bacteria in the
      oral cavity through the use of an antiseptic mouthwash. CONCLUSIONS: Long-term
      dietary nitrate supplementation may represent a novel nutrition-based strategy to
      enhance ischemia-induced revascularization.

PMID- 22992323
TI  - Beets, bacteria, and blood flow: a lesson of three Bs.

PMID- 22992324
TI  - Professor De Clercq and 25 years of international collaboration on antiviral
      research.
AB  - Professor Erik De Clercq, recent recipient of the International Society for
      Antiviral Research (ISAR) 'Outstanding Contributions to the Society Award',
      recounts 25 years of antiviral research collaborating with his colleagues and
      friends in Japan.

PMID- 22992326
TI  - Resection with total caudate lobectomy confers survival benefit in hilar
      cholangiocarcinoma of Bismuth type III and IV.
AB  - PURPOSE: To identify prognostic predictors for overall survival of patients with
      hilar cholangiocarcinoma of Bismuth type III and IV (HCBT34), and to determine
      survival benefit and safety of total caudate lobectomy (TCL) in a Chinese centre.
      METHODS: From January 2001 to December 2010, 171 patients with the diagnosis of
      HCBT34, who underwent a potentially curative resection, were included in this
      study. Cox proportional hazards regression models were used to determine the
      association between possible prognostic variables and survival time. Curative
      resectability rate, morbidity and mortality were investigated also. RESULTS:
      Resection with TCL was significantly associated with more opportunity to achieve
      curative resection (p < 0.01), did not accompany with more morbidity (p = 0.39)
      and mortality (p = 0.67). Cox regression analysis demonstrated positive resection
      margins [Relative Risk (RR) 3.6, 95% CI 3.5-3.7], not well differentiation (RR
      2.9, 95% CI 2.7-3.1), higher preoperative serum peak CA19-9 level (RR 1.6, 95% CI
      1.5-1.7) and regional lymph nodes involvement (RR 1.5, 95% CI 1.4-1.6) as
      independent adverse prognostic variables. CONCLUSIONS: Resection with TCL offers
      a long-term survival opportunity for HCBT34, with high curative resectability
      rates and an acceptable safety profile.

PMID- 22992327
TI  - Sample size and power considerations in network meta-analysis.
AB  - BACKGROUND: Network meta-analysis is becoming increasingly popular for
      establishing comparative effectiveness among multiple interventions for the same
      disease. Network meta-analysis inherits all methodological challenges of standard
      pairwise meta-analysis, but with increased complexity due to the multitude of
      intervention comparisons. One issue that is now widely recognized in pairwise
      meta-analysis is the issue of sample size and statistical power. This issue,
      however, has so far only received little attention in network meta-analysis. To
      date, no approaches have been proposed for evaluating the adequacy of the sample
      size, and thus power, in a treatment network. FINDINGS: In this article, we
      develop easy-to-use flexible methods for estimating the 'effective sample size'
      in indirect comparison meta-analysis and network meta-analysis. The effective
      sample size for a particular treatment comparison can be interpreted as the
      number of patients in a pairwise meta-analysis that would provide the same degree
      and strength of evidence as that which is provided in the indirect comparison or
      network meta-analysis. We further develop methods for retrospectively estimating
      the statistical power for each comparison in a network meta-analysis. We
      illustrate the performance of the proposed methods for estimating effective
      sample size and statistical power using data from a network meta-analysis on
      interventions for smoking cessation including over 100 trials. CONCLUSION: The
      proposed methods are easy to use and will be of high value to regulatory agencies
      and decision makers who must assess the strength of the evidence supporting
      comparative effectiveness estimates.

PMID- 22992328
TI  - Pulmonary fibrosis and lymphocytic alveolitis associated with triple
      antiphospholipid antibody positivity: a diagnostic puzzle.

PMID- 22992329
TI  - Antitumor activity of motesanib alone and in combination with cisplatin or
      docetaxel in multiple human non-small-cell lung cancer xenograft models.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) is categorized into various
      histologic subtypes that play an important role in prognosis and treatment
      outcome. We investigated the antitumor activity of motesanib, a selective
      antagonist of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3,
      platelet-derived growth factor receptor, and Kit, alone and combined with
      chemotherapy in five human NSCLC xenograft models (A549, Calu-6, NCI-H358, NCI
      H1299, and NCI-H1650) containing diverse genetic mutations. RESULTS: Motesanib as
      a single agent dose-dependently inhibited tumor xenograft growth compared with
      vehicle in all five of the models (P < 0.05). When combined with cisplatin,
      motesanib significantly inhibited the growth of Calu-6, NCI-H358, and NCI-H1650
      tumor xenografts compared with either single agent alone (P < 0.05). Similarly,
      the combination of motesanib plus docetaxel significantly inhibited the growth of
      A549 and Calu-6 tumor xenografts compared with either single agent alone (P <
      0.05). In NCI-H358 and NCI-H1650 xenografts, motesanib with and without cisplatin
      significantly decreased tumor blood vessel area (P < 0.05 vs vehicle) as assessed
      by anti-CD31 staining. Motesanib alone or in combination with chemotherapy had no
      effect on tumor cell proliferation in vitro. CONCLUSIONS: These data demonstrate
      that motesanib had antitumor activity against five different human NSCLC
      xenograft models containing diverse genetic mutations, and that it had enhanced
      activity when combined with cisplatin or docetaxel. These effects appeared to be
      mediated primarily by antiangiogenic mechanisms.

PMID- 22992330
TI  - Genetic correlate of cognitive training response in schizophrenia.
AB  - Intensive computerized auditory training results in improved cognition for
      schizophrenia patients, but participants show variation in their cognitive gains
      and the biological factors that affect the response to training are unknown.
      Single nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT)
      gene have been related to cognitive function. Here we asked if functional
      variation in this gene has an impact on the response of schizophrenia patients to
      cognitive training. We genotyped 48 schizophrenia patients who completed 50 h of
      computerized cognitive training and analyzed the association between DNA variants
      in the COMT gene and the improvement in global cognition. Although conventional
      analyses did not reveal any significant associations, a set-based analysis
      examining the aggregate effect of common variation in the COMT gene (42 SNPs)
      suggested association with improvement in global cognition. Eight SNPs, mostly
      located in the 3' end of the COMT gene, were nominally associated with
      improvement in cognition. These data suggest that genotype influences the
      response to intensive cognitive training in schizophrenia, and may indicate that
      cognitive training regimens need to be personalized to the underlying
      biosignatures of each individual patient. This article is part of a Special Issue
      entitled 'Cognitive Enhancers'.

PMID- 22992331
TI  - Cognitive impairment in major depression and the mGlu2 receptor as a therapeutic
      target.
AB  - Cognitive impairment, in particular of attention and memory, is often reported by
      patients suffering from major depressive disorder (MDD) and deficits in attention
      are part of the current diagnostic criteria of MDD. Objectively measured
      cognitive deficits associated with MDD have been described in many studies. They
      have been conceptualized as an integral facet and epiphenomenon of MDD. However,
      evidence accumulated in recent years has challenged this notion and demonstrated
      that in a subset of patients the degree of cognitive deficits cannot be accounted
      for by the severity of depression. In addition, in some patients cognitive
      deficits persist despite resolution of depressive symptomatology. It is plausible
      to assume that cognitive deficits contribute to functional impairment even though
      supportive data for such a relationship are lacking. However, the exact
      association between cognitive deficits and major depression and the clinical and
      neurobiological characteristics of patients with MDD in whom cognitive deficits
      seem partially or fully independent of the clinical manifestation of depressive
      symptoms remain poorly understood. This review focuses on objective measures of
      non-emotional cognitive deficits in MDD and discusses the presence of a subgroup
      of patients in whom these symptoms can be defined independently and in
      dissociation from the rest of the depressive symptomatology. The current
      understanding of brain circuits and molecular events implicated in cognitive
      impairment in MDD are discussed with an emphasis on the missing elements that
      could further define the specificity of cognitive impairment in MDD and lead to
      new therapeutics. Furthermore, this article presents in detail observations made
      in behavioral studies in rodents with potential novel therapeutic agents, such as
      negative allosteric modulators at the metabotropic glutamate receptor type 2/3
      (mGlu2/3 NAM) which exhibit both cognitive enhancing and antidepressant
      properties. Such a compound, RO4432717, was tested in tests of short term memory
      (delayed match to position), cognitive flexibility (Morris water maze, reversal
      protocol), impulsivity and compulsivity (5-choice serial reaction time) and
      spontaneous object recognition in rodents, providing first evidence of a profile
      potentially relevant to address cognitive impairment in MDD. This article is part
      of a Special Issue entitled 'Cognitive Enhancers'.

PMID- 22992332
TI  - Valproic acid but not D-cycloserine facilitates sleep-dependent offline learning
      of extinction and habituation of conditioned fear in humans.
AB  - The effectiveness of D-cycloserine (DCS), an N-methyl-D-aspartate glutamate
      receptor partial agonist, and valproic acid (VPA), a histone deacetylase
      inhibitor, in facilitating the extinction of fear-conditioned memory has been
      explored in humans and animals. Here, we confirmed whether DCS (100 mg) and VPA
      (400 mg) act in off-line learning processes during sleep or waking, for further
      clinical application to anxiety disorders and posttraumatic stress disorder
      (PTSD). We performed a randomized, blind, placebo-controlled clinical trial in 90
      healthy adults. Visual cues and electric shocks were used as the conditioned
      stimulus (CS) and unconditioned stimulus (US), respectively. The extinction
      effect was observed not in simple recall after the extinction of coupled CS-US,
      but was observed in the post-re-exposure phase after unexpected re-exposure to
      reinstatement CS-US coupling. Newly acquired conditioned fear was also eliminated
      or habituated by DCS and VPA administration, in line with previous findings.
      Furthermore, VPA facilitated the off-line learning process of conditioned fear
      extinction and habituation during sleep, while DCS facilitated this process
      during waking. These novel findings suggest that DCS and VPA might enhance
      exposure-based cognitive therapy for anxiety disorders and PTSD by reducing the
      vulnerability to reinstatement and preventing relapses of fear-conditioned
      responses, and provide evidence for a peculiarity of the sleep-dependent off-line
      learning process for conditioned fear extinction. This article is part of a
      Special Issue entitled 'Cognitive Enhancers'.

PMID- 22992333
TI  - Understanding Australian healthcare workers' uptake of influenza vaccination:
      examination of public hospital policies and procedures.
AB  - BACKGROUND: In Australia, whether to provide free influenza vaccine to health
      care workers (HCWs) is a policy decision for each hospital or jurisdiction, and
      is therefore not uniform across the country. This study explored hospital
      policies and practices regarding occupational influenza vaccination of HCWs in
      Australia. METHODS: A study using qualitative methodology, which included semi
      structured interviews, was undertaken with hospital staff involved with the
      delivery of occupational influenza vaccination from three states in Australia.
      RESULTS: The 29 participants were responsible for vaccinating staff in 82
      hospitals. Major themes in the responses were the lack of resources and the
      difficulties participants faced in procuring any additional support or funding
      from their institutions. All study sites provided vaccine free of charge to
      employees via on-site clinics or mobile carts, and used multiple strategies to
      inform and educate their staff. In some instances, declination forms had been
      adopted, however their use was associated with resourcing issues, animosity, and
      other problems. Participants who were responsible for multiple sites were more
      likely to recount lower vaccination coverage figures at their hospitals.
      CONCLUSIONS: From these interviews, it is clear that hospitals are implementing
      multiple strategies to educate, promote, and deliver the vaccine to staff.
      However, resources and support are not always available to assist with the
      vaccination campaign. The reality for many hospitals is that there is limited
      capacity to implement the vaccination campaigns at the levels high enough to
      raise compliance rates. Further research needs to be conducted to quantify the
      factors contributing to higher uptake in the Australian hospital setting.

PMID- 22992334
TI  - Dynamic subcellular localization of the mono-ADP-ribosyltransferase ARTD10 and
      interaction with the ubiquitin receptor p62.
AB  - BACKGROUND: ADP-ribosylation is a posttranslational modification catalyzed in
      cells by ADP-ribosyltransferases (ARTD or PARP enzymes). The ARTD family consists
      of 17 members. Some ARTDs modify their substrates by adding ADP-ribose in an
      iterative process, thereby synthesizing ADP-ribose polymers, the best-studied
      example being ARTD1/PARP1. Other ARTDs appear to mono-ADP-ribosylate their
      substrates and are unable to form polymers. The founding member of this latter
      subclass is ARTD10/PARP10, which we identified as an interaction partner of the
      nuclear oncoprotein MYC. Biochemically ARTD10 uses substrate-assisted catalysis
      to modify its substrates. Our previous studies indicated that ARTD10 may shuttle
      between the nuclear and cytoplasmic compartments. We have now addressed this in
      more detail. RESULTS: We have characterized the subcellular localization of
      ARTD10 using live-cell imaging techniques. ARTD10 shuttles between the
      cytoplasmic and nuclear compartments. When nuclear, ARTD10 can interact with MYC
      as measured by bimolecular fluorescence complementation. The shuttling is
      controlled by a Crm1-dependent nuclear export sequence and a central ARTD10
      region that promotes nuclear localization. The latter lacks a classical nuclear
      localization sequence and does not promote full nuclear localization. Rather this
      non-conventional nuclear localization sequence results in an equal distribution
      of ARTD10 between the cytoplasmic and the nuclear compartments. ARTD10 forms
      discrete and dynamic bodies primarily in the cytoplasm but also in the nucleus.
      These contain poly-ubiquitin and co-localize in part with structures containing
      the poly-ubiquitin receptor p62/SQSTM1. The co-localization depends on the
      ubiquitin-associated domain of p62, which mediates interaction with poly
      ubiquitin. CONCLUSIONS: Our findings demonstrate that ARTD10 is a highly dynamic
      protein. It shuttles between the nuclear and cytosolic compartments dependent on
      a classical nuclear export sequence and a domain that mediates nuclear uptake.
      Moreover ARTD10 forms discrete bodies that exchange subunits rapidly. These
      bodies associate at least in part with the poly-ubiquitin receptor p62. Because
      this protein is involved in the uptake of cargo into autophagosomes, our results
      suggest a link between the formation of ARTD10 bodies and autophagy. LAY  Post
      translational modifications refer to changes in the chemical appearance of
      proteins and occur, as the name implies, after proteins have been synthesized.
      These modifications frequently affect the behavior of proteins, including
      alterations in their activity or their subcellular localization. One of these
      modifications is the addition of ADP-ribose to a substrate from the cofactor
      NAD+. The enzymes responsible for this reaction are ADP-ribosyltransferases
      (ARTDs or previously named PARPs). Presently we know very little about the role
      of mono-ADP-ribosylation of proteins that occurs in cells. We identified ARTD10,
      a mono-ADP-ribosyltransferase, as an interaction partner of the oncoprotein MYC.
      In this study we have analyzed how ARTD10 moves within a cell. By using different
      live-cell imaging technologies that allow us to follow the position of ARTD10
      molecules over time, we found that ARTD10 shuttles constantly in and out of the
      nucleus. In the cytosol ARTD10 forms distinct structures or bodies that
      themselves are moving within the cell and that exchange ARTD10 subunits rapidly.
      We have identified the regions within ARTD10 that are required for these
      movements. Moreover we defined these bodies as structures that interact with p62.
      This protein is known to play a role in bringing other proteins to a structure
      referred to as the autophagosome, which is involved in eliminating debris in
      cells. Thus our work suggests that ARTD10 might be involved in and is regulated
      by ADP-riboslyation autophagosomal processes.

PMID- 22992335
TI  - The nutritional status of children in Bhutan: results from the 2008 National
      Nutrition Survey and trends over time.
AB  - BACKGROUND: There are few reports on the nutritional status of Bhutanese
      children. The objective of this paper is to summarize results from the 2008
      National Nutrition Survey and to describe progress achieved during the last two
      decades. METHODS: A cross-sectional survey of 2376 children aged 6 to 59 months
      was conducted during November-December 2008 to provide national and regional
      estimates. A multi-stage cluster sampling method was applied and 40
      gewogs/thromdes were selected from each region (Western, Central, Eastern).
      Guidelines on how to measure length/height and weight followed WHO standardized
      procedures. Data were analysed for consistency and validation using the software
      WHO Anthro and the WHO SPSS macro. Underweight, stunting, overweight, wasting and
      thinness were defined based on the WHO Child Growth Standards. Data from 1986-88
      and 1999 national surveys were reanalysed using the WHO standards to describe
      trends in nutritional status. RESULTS: Nationally, 34.9% Bhutanese preschool
      children are stunted and 10.4% are underweight. Wasting is 4.7%, with severe
      wasting close to 2% in rural areas, while overweight affects 4.4% of preschool
      children. While underweight rates are similar across regions, wasting is
      substantially more prevalent in the Western region and stunting in the Eastern
      region. Stunting shows a steep rise during the first two years of life, as high
      as 40%, and levels off thereafter, while wasting is greatest among children aged
      6-24 months and subsequently decreases. The prevalence of stunting fell from
      60.9% in 1986-88 to 34.9% in 2008, and underweight declined from 34.0% to 10.4%
      during same period. The percentage of wasted children dropped from 5.2% in 1986
      88 to 2.5% in 1999 but then increased to 4.7% in 2008. CONCLUSIONS: There have
      been major improvements in the nutritional status of Bhutanese children over the
      past two decades, however, linear growth retardation remains a significant
      concern. Early identification of growth faltering is essential for improving the
      effectiveness of public health programs to prevent stunting. Similarly, wasting
      rates indicate the need for a system to identify children with severe
      malnutrition in the isolated communities so that they can receive appropriate
      care.

PMID- 22992336
TI  - Bioinformatics and evolutionary insight on the spike glycoprotein gene of QX-like
      and Massachusetts strains of infectious bronchitis virus.
AB  - BACKGROUND: Infectious bronchitis virus (IBV) is a Gammacoronavirus of the family
      Coronaviridae and is a causative agent of an economically important disease in
      poultry. The spike glycoprotein of IBV is essential for host cell attachment,
      neutralization, and is involved in the induction of protective immunity.
      Previously obtained sequence data of the spike gene of IBV QX-like and
      Massachusetts strains were subjected to bioinformatics analysis. FINDINGS: On
      analysis of potential phosphorylation sites, the Ser542 and Ser563 sites were not
      present in Massachusetts strains, while QX-like isolates did not have the Ser534
      site. Massachusetts and QX-like strains showed different cleavage site motifs.
      The N-glycosylation sites ASN-XAA-SER/THR-55, 147, 200 and 545 were additionally
      present in QX-like strains. The leucine-rich repeat regions in Massachusetts
      strains consisted of stretches of 63 to 69 amino acids, while in the QX-like
      strains they contained 59 amino acids in length. An additional palmitoylation
      site was observed in CK/SWE/082066/2010 a QX-like strain. Primary structure data
      showed difference in the physical properties and hydrophobic nature of both
      genotypes. The comparison of secondary structures revealed no new structural
      domains in the genotypic variants. The phylogenetic analyses based on avian and
      mammalian coronaviruses showed the analysed IBV as closely related to turkey
      coronaviruses and distantly related to thrush and munia coronaviruses.
      CONCLUSION: The study demonstrated that spike glycoprotein of the Massachusetts
      and the QX-like variants of IBV are molecularly distinct and that this may
      reflect in differences in the behavior of these viruses in vivo.

PMID- 22992337
TI  - Retinoids and breast cancer: new clues to increase their activity and
      selectivity.
AB  - All-trans retinoic acid and derivatives (retinoids) are promising agents in the
      management of certain hematologic malignancies and solid tumors, including breast
      cancer. Retinoids are endowed with anti-proliferative, cyto-differentiating and
      apoptotic effects that are largely mediated by activation of the nuclear hormone
      retinoic acid receptors RARalpha, RARbeta and RARgamma. These are ligand
      dependent transcriptional factors controlling the expression of numerous genes.
      The relative importance of each receptor subtype for the anti-tumor activity of
      retinoids is largely unknown. Clarification of this point is of fundamental
      importance for the rational design of retinoid-based therapeutic approaches aimed
      at controlling a heterogeneous type of tumors, like breast cancer. 

PMID- 22992339
TI  - Interstitial pneumonia associated with MPO-ANCA: clinicopathological features of
      nine patients.
AB  - Myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) is a well
      known marker for small vessel vasculitis. Recent reports have demonstrated that
      interstitial pneumonia (IP) may rarely be associated with serum MPO-ANCA. Yet,
      little is known about the histological features. We reviewed surgical lung biopsy
      from nine patients with IP of uncertain etiology with serum MPO-ANCA. There was a
      male predominance (6:3) with a median age of 62.1. Histologically, eight patients
      presented with a usual interstitial pneumonia (UIP) pattern of pulmonary
      fibrosis, frequently accompanied by areas of nonspecific interstitial pneumonia
      (NSIP) pattern. One patient showed diffuse alveolar damage (DAD), and two
      patients showed mixture of UIP and DAD reflecting acute exacerbation of UIP.
      Microscopic honeycomb cysts were common, but fibroblastic foci were
      inconspicuous. The most frequent additional findings were small airway disease
      (9/9), and lymphoid follicles (7/9). Neither capillaritis nor vasculitis was seen
      in any of our cases. Three patients had microscopic hematuria, but none
      progressed to microscopic polyangiitis during the follow up. Mortality rate was
      44% (median follow up 39.1 months). IP associated with MPO-ANCA showed
      characteristic histology dominated by UIP pattern. Vasculitis was not identified
      in our cohort, but small airways disease and lymphoid follicles were present in
      most cases. IP associated with MPO-ANCA may be a histologically distinctive
      disease from idiopathic pulmonary fibrosis. Mortality was relatively high and
      life threatening acute exacerbation may occur.

PMID- 22992338
TI  - Molecular predictors of response to tyrosine kinase inhibitors in patients with
      Non-Small-Cell Lung Cancer.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) have become a treatment option in non-small-cell lung cancer (NSCLC)
      patients. However, despite their use in this disease, a significant number of
      patients will eventually develop resistance and relapse. In this study, we aimed
      to characterize several molecular events involved in potential resistance
      mechanisms to anti-EGFR treatment and correlate our findings with clinical
      outcome. MATERIAL AND METHODS: The medical records of patients with NSCLC who
      received anti-EGFR TKIs in any line within the participating centers were
      reviewed and available paraffin embedded tissue was retrieved. Mutational
      analysis for EGFR, KRAS, BRAF and intron-exon 14 deletions of MET; FISH analysis
      for chromosomal gain or amplification for EGFR, MET and the deletion marker
      D7S486 were performed. Furthermore, the expression of EGFR and MET were analysed
      by immunohistochemistry. All results were correlated with treatment outcomes.
      RESULTS: Between 10/2001 and 12/2009 from an initial cohort of 72 treated
      patients, 59 cases (28 gefitinib/ 31 erlotinib) were included in the analysis.
      The majority had adenocarcinoma histology (68%), and received treatment in the
      second line setting (56%). Disease control rate (DCR) was 25.4% for all patients.
      EGFR and RAS mutational rates were 33% and 10% respectively, no other mutations
      were identified. High EGFR expressing tumors were found in 7 of 45 cases and
      pEGFR positivity (IHC) was found in 56% of the cases; MET expression was found in
      48% of tumors. EGFR gene amplification was found in 4 cases, two cases showed
      high polysomy; overall, 13% cases were FISH positive for EGFR. High polysomy of
      MET gene was detected in 1/43 cases tested. D7S486 locus deletion was detected in
      15/37 (40%) of cases. EGFR mutational status and gene gain were both associated
      with more favorable DCR. No other associations between examined biomarkers and
      DCR or survival were noted. CONCLUSIONS: EGFR mutational status is a predictor
      for disease control in patients with NSCLC treated with anti-EGFR TKIs. The
      predictive role of several other molecules involved in potential resistance to
      anti-EGFR TKIs is worthy of additional investigation.

PMID- 22992340
TI  - [Cholera epidemics on Reunion Island during the 19th century].
AB  - The first cholera outbreak on Bourbon Island (now Reunion Island) was recorded in
      January 1820. The disease was imported from Mauritius Island aboard the steamer
      Pivert. The epidemic began on Mauritius in November 1819 after the English
      frigate, La Topaze, called from Calcutta, India. Dr. Francois Vinson demonstrated
      the transmissibility of cholera during this epidemic. Drastic sanitary measures
      spared Reunion from the two epidemics on Mauritius Island, in 1854 and 1856. The
      second outbreak of cholera on Reunion Island was recorded on March 6, 1859. The
      disease was introduced from East Africa by the steamer Mascareignes, which
      carried indentured servants. The captain (d'Agnel) et the supercargo (Menon) of
      the steamer claimed to the doctor who boarded the ship before landing that no
      passengers or crew had had cholera, in flagrant contradiction to the autopsy
      report issued by Navy surgeon Alfred Vaillant, who had concluded that cholera was
      present when the vessel left the African coast. This report was withheld from the
      boarding physician. Cholera spread quickly on the island and affected the poorest
      people, especially freed slaves, most severely. Dr. Petit, the chief Navy
      Physician and Director of the Health Department, obtained a confession by Menon
      about the fraudulent statements. On January 24, 1860, a trial for public health
      endangerment began on Reunion Island; it ended on February 1 with a not-guilty
      verdict, based largely on the testimony of several island doctors that cholera
      was not contagious.

PMID- 22992341
TI  - Ischaemic heart disease mortality and years of work in trucking industry workers.
AB  - OBJECTIVES: Evidence from general population-based studies and occupational
      cohorts has identified air pollution from mobile sources as a risk factor for
      cardiovascular disease. In a cohort of US trucking industry workers, with regular
      exposure to vehicle exhaust, the authors previously observed elevated
      standardised mortality ratios for ischaemic heart disease (IHD) compared with
      members of the general US population. Therefore, the authors examined the
      association of increasing years of work in jobs with vehicle exhaust exposure and
      IHD mortality within the cohort. METHODS: The authors calculated years of work in
      eight job groups for 30,758 workers using work records from four nationwide
      companies. Proportional hazard regression was used to examine relationships
      between IHD mortality, 1985-2000, and employment duration in each job group.
      RESULTS: HRs for at least 1 year of work in each job were elevated for
      dockworkers, long haul drivers, pick-up and delivery drivers, combination
      workers, hostlers, and shop workers. There was a suggestion of an increased risk
      of IHD mortality with increasing years of work as a long haul driver, pick-up and
      delivery driver, combination worker, and dockworker. CONCLUSION: These results
      suggest an elevated risk of IHD mortality in workers with a previous history of
      regular exposure to vehicle exhaust.

PMID- 22992342
TI  - Improvement of quality of life and survival using self-expandable metal stent
      placement for severe malignant stenosis of the gastric body: a case report.
AB  - INTRODUCTION: Advanced gastric carcinoma often decreases quality of life because
      of upper gastrointestinal tract stenosis. Self-expandable metal stents have been
      thought to be an effective, minimally invasive treatment for stenosis. However,
      the effectiveness of self-expandable metal stent placement for carcinomatous
      stenosis of the gastric body and antrum has not been clarified, and there have
      been few reports of such cases. CASE PRESENTATION: A 74-year-old Japanese woman
      developed stenosis of the gastric body and antrum caused by advanced gastric
      cancer during first-line chemotherapy. She developed weight loss and poor
      nutrition due to inadequate intake. Self-expandable metal stent placement for
      stenosis of the gastric body and antrum ameliorated her symptoms rapidly and
      improved her general condition and quality of life. Eight days after self
      expandable metal stent placement, second-line chemotherapy could be administered
      safely. Oral intake and nutritional status were maintained for 117 days after
      self-expandable metal stent placement, and she died of gastric cancer 176 days
      after self-expandable metal stent placement and initiation of second-line
      chemotherapy. CONCLUSIONS: Self-expandable metal stent placement for
      carcinomatous stenosis in the gastric body and antrum could be an effective
      therapeutic strategy for patients with inadequate oral uptake. It may provide
      rapid improvement of the patient's general condition and oral intake with minimal
      complications, comparatively long-term symptom relief, and a survival benefit by
      allowing second-line chemotherapy.

PMID- 22992343
TI  - microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF
      kappaB by targeting CARD10 and COPS8 in gastric cancer.
AB  - BACKGROUND: Gastric cancer is the second most common cause of cancer-related
      death in the world. Inflammatory signals originating from gastric cancer cells
      are important for recruiting inflammatory cells and regulation of metastasis of
      gastric cancer. Several microRNAs (miRNA) have been shown to be involved in
      development and progression of gastric cancer. miRNA-146a (miR-146a) is a
      modulator of inflammatory signals, but little is known about its importance in
      gastric cancer. We therefore wanted to identify targets of miR-146a in gastric
      cancer and examine its biological roles. RESULTS: The expression of miR-146a was
      evaluated by quantitative PCR (qPCR) and found up-regulated in the gastrin
      knockout mice, a mouse model of gastric cancer, and in 73% of investigated human
      gastric adenocarcinomas. Expression of miR-146a by gastric cancer cells was
      confirmed by in situ hybridization. Global analysis of changes in mRNA levels
      after miR-146a transfection identified two transcripts, caspase recruitment
      domain-containing protein 10 (CARD10) and COP9 signalosome complex subunit 8
      (COPS8), as new miR-146a targets. qPCR, Western blotting and luciferase assays
      confirmed these transcripts as direct miR-146a targets. CARD10 and COPS8 were
      shown to be part of the G protein-coupled receptor (GPCR) pathway of nuclear
      factor-kappaB (NF-kappaB) activation. Lysophosphatidic acid (LPA) induces NF
      kappaB activation via this pathway and over-expression of miR-146a inhibited LPA
      induced NF-kappaB activation, reduced LPA-induced expression of tumor-promoting
      cytokines and growth factors and inhibited monocyte attraction. CONCLUSIONS: miR
      146a expression is up-regulated in a majority of gastric cancers where it targets
      CARD10 and COPS8, inhibiting GPCR-mediated activation of NF-kappaB, thus reducing
      expression of NF-kappaB-regulated tumor-promoting cytokines and growth factors.
      By targeting components of several NF-kappaB-activating pathways, miR-146a is a
      key component in the regulation of NF-kappaB activity.

PMID- 22992344
TI  - Insight into the bacterial gut microbiome of the North American moose (Alces
      alces).
AB  - BACKGROUND: The work presented here provides the first intensive insight into the
      bacterial populations in the digestive tract of the North American moose (Alces
      alces). Eight free-range moose on natural pasture were sampled, producing eight
      rumen samples and six colon samples. Second generation (G2) PhyloChips were used
      to determine the presence of hundreds of operational taxonomic units (OTUs),
      representing multiple closely related species/strains (>97% identity), found in
      the rumen and colon of the moose. RESULTS: A total of 789 unique OTUs were used
      for analysis, which passed the fluorescence and the positive fraction thresholds.
      There were 73 OTUs, representing 21 bacterial families, which were found
      exclusively in the rumen samples: Lachnospiraceae, Prevotellaceae and several
      unclassified families, whereas there were 71 OTUs, representing 22 bacterial
      families, which were found exclusively in the colon samples: Clostridiaceae,
      Enterobacteriaceae and several unclassified families. Overall, there were 164
      OTUs that were found in 100% of the samples. The Firmicutes were the most
      dominant bacteria phylum in both the rumen and the colon. Microarray data
      available at ArrayExpress, accession number E-MEXP-3721. CONCLUSIONS: Using
      PhyloTrac and UniFrac computer software, samples clustered into two distinct
      groups: rumen and colon, confirming that the rumen and colon are distinct
      environments. There was an apparent correlation of age to cluster, which will be
      validated by a larger sample size in future studies, but there were no detectable
      trends based upon gender.

PMID- 22992345
TI  - Pleuritis is a red flag for adult-onset Still's disease which may require
      biologic therapies.

PMID- 22992346
TI  - The fallacy of the equity-efficiency trade off: rethinking the efficient health
      system.
AB  - In the health systems literature one can see discussions about the trade off
      between the equity achievable by the system and its efficiency. Essentially it is
      argued that as greater health equity is achieved, so the level of efficiency will
      diminish. This argument is borrowed from economics literature on market
      efficiency. In the application of the economic argument to health, however,
      serious errors have been made, because it is quite reasonable to talk of both
      health equity being a desirable output of a health system, and the efficient
      production of that output. In this article we discuss notions of efficiency, and
      the equity-efficiency trade off, before considering the implications of this for
      health systems.

PMID- 22992347
TI  - Are community midwives addressing the inequities in access to skilled birth
      attendance in Punjab, Pakistan? Gender, class and social exclusion.
AB  - BACKGROUND: Pakistan is one of the six countries estimated to contribute to over
      half of all maternal deaths worldwide. To address its high maternal mortality
      rate, in particular the inequities in access to maternal health care services,
      the government of Pakistan created a new cadre of community-based midwives (CMW).
      A key expectation is that the CMWs will improve access to skilled antenatal and
      intra-partum care for the poor and disadvantaged women. A critical gap in our
      knowledge is whether this cadre of workers, operating in the private health care
      context, will meet the expectation to provide care to the poorest and most
      marginalized women. There is an inherent paradox between the notions of fee-for
      service and increasing access to health care for the poorest who, by definition,
      are unable to pay. METHODS/DESIGN: Data will be collected in three interlinked
      modules. Module 1 will consist of a population-based survey in the catchment
      areas of the CMW's in districts Jhelum and Layyah in Punjab. Proportions of
      socially excluded women who are served by CMWs and their satisfaction levels with
      their maternity care provider will be assessed. Module 2 will explore, using an
      institutional ethnographic approach, the challenges (organizational, social,
      financial) that CMWs face in providing care to the poor and socially marginalized
      women. Module 3 will identify the social, financial, geographical and other
      barriers to uncover the hidden forces and power relations that shape the choices
      and opportunities of poor and marginalized women in accessing CMW services. An
      extensive knowledge dissemination plan will facilitate uptake of research
      findings to inform positive developments in maternal health policy, service
      design and care delivery in Pakistan. DISCUSSION: The findings of this study will
      enhance understanding of the power dynamics of gender and class that may underlie
      poor women's marginalization from health care systems, including community
      midwifery care. One key outcome will be an increased sensitization of the special
      needs of socially excluded women, an otherwise invisible group. Another
      expectation is that the poor, socially excluded women will be targeted for
      provision of maternity care. The research will support the achievement of the 5th
      Millennium Development Goal in Pakistan.

PMID- 22992348
TI  - Association between inherited thrombophilia and impaired right ventricular
      function in deep vein thrombosis without symptomatic pulmonary embolism.
AB  - The aim was to evaluate the right ventricular function in patients with inherited
      thrombophilia and deep vein thrombosis (DVT) without pulmonary embolism. A total
      of 38 patients with DVT without symptomatic pulmonary embolism and 30 patients
      with varicose veins were enrolled. Clinical data, echocardiography, and 2
      thrombophilic mutations were analyzed. Factor V Leiden (FVL) polymorphism was
      significantly frequent in the study group (P = .007). The difference in
      prothrombin G20210A polymorphism between the study and control groups was at a
      near-significant level (P = .058). There was statistically significant decrease
      in tricuspid annular plane systolic excursion values in patients with FVL and
      prothrombin G20210A polymorphism. Combined FVL and prothrombin G20210A
      polymorphisms were more closely related to the decrease in this value (P = .006).
      Deep vein thrombosis had no additional adverse effects on right ventricle.
      Impaired right ventricular systolic function occurs in FVL and prothrombin
      G20210A polymorphisms. 

PMID- 22992349
TI  - Correlation of neutrophil to lymphocyte ratio with the presence and severity of
      metabolic syndrome.
AB  - PURPOSE: The aim of this study is to investigate the relationship between the
      criteria comprising metabolic syndrome (MS) and neutrophil-lymphocyte ratio
      (NLR), a simple and reliable indicator of inflammation. METHOD: Seventy patients
      with MS and 71 age- and sex-matched control participants were included. Patients
      were classified into 3 groups based on the number of MS criteria: group 1 (with 3
      criteria), group 2 (with 4 criteria), and group 3 (with 5 criteria). The NLR was
      calculated from complete blood count. RESULTS: Patients with MS had significantly
      higher NLR compared to the control group. Moreover, the group 3 patients had
      higher NLR than those in groups 2 and 1 (P = .008 and P = .078, respectively),
      whereas there was no difference between the patients meeting 3 and 4 MS criteria
      (P = .320). Besides, NLR increased as the severity of MS increased (r = .586, P <
      .001). The cutoff level for NLR with optimal sensitivity and specificity was
      calculated as 1.84. Serum glucose and high-sensitive C-reactive protein level
      were found to be independent predictors of an NLR value greater than 1.84.
      CONCLUSION: The present study indicated a significant correlation between the
      criteria of MS and inflammation on the basis of NLR. Furthermore, there an
      increase in NLR as the severity of MS increases.

PMID- 22992351
TI  - Antiviral drug development--success and failure: a personal perspective with a
      Japanese connection.
AB  - At the 25th International Conference on Antiviral Research, I received a special
      recognition for my contribution to the International Society of Antiviral
      Research over a period of 25 years (from 1987 until 2012). This review follows
      the theme of my presentation at that event, which comprised 10 reminiscences, all
      with a Japanese connection concerning the success, or otherwise, in the clinical
      development of: double- and single-stranded polynucleotides; suramin, a
      polysulfonate; dextran sulfate, a polysulfate; brivudin; BVaraU; 2',3'
      dideoxynucleoside analogues; HEPT; adefovir and tenofovir; CXCR4 antagonists; and
      elvitegravir.

PMID- 22992352
TI  - Road traffic noise: annoyance, sleep disturbance, and public health implications.
AB  - BACKGROUND: The WHO has recognized environmental noise as harmful pollution that
      causes adverse psychosocial and physiologic effects (i.e., annoyance and sleep
      disturbance) on human health. In Europe, noise-related health studies have been
      actively conducted, but the U.S. has lagged behind in this research field.
      PURPOSE: This research predicted ambient levels of road traffic noise for a
      highly urbanized area: Fulton County GA. Assessment was made of noise impacts on
      the population, focusing on annoyance and sleep disturbance. METHODS: All the
      data sets were collected during 2009-2011, and data analysis was performed in
      2010-2011. The study used a sound-propagation model for noise-level prediction
      and derived noise-impact indicators for annoyance and sleep disturbance from
      exposure-response models. Then, annoyed and sleep-disturbed populations were
      predicted with the use of each noise-impact indicator. RESULTS: It was predicted
      that 109,967 people would be at risk of being highly annoyed, with 19,621 people
      at risk for high sleep disturbance for Fulton County GA. Noise-impact indicators
      such as the percentage of those who were highly annoyed and who had high levels
      of sleep disturbance were expected to be valuable metrics to compare noise equity
      among urban communities. CONCLUSIONS: Many residents of the greater Atlanta area
      may be exposed to noise levels that put them at risk of being highly annoyed or
      having high levels of sleep disturbance. These results, if generalized to other
      urban areas with high levels of road traffic, indicate that it may be important
      for the public's health to update existing noise-related policies or develop new
      ones to control and abate noise concerns in urban communities.

PMID- 22992350
TI  - Socioeconomic inequalities in occupational, leisure-time, and transport related
      physical activity among European adults: a systematic review.
AB  - BACKGROUND: This study systematically reviewed the evidence pertaining to
      socioeconomic inequalities in different domains of physical activity (PA) by
      European region. METHODS: Studies conducted between January 2000 and December
      2010 were identified by a systematic search in Pubmed, Embase, Web of Science,
      Psychinfo, Sportdiscus, Sociological Abstracts, and Social Service Abstracts.
      English-language peer-reviewed studies undertaken in the general population of
      adults (18-65 years) were classified by domain of PA (total, leisure-time
      including sport, occupational, active transport), indicator of socioeconomic
      position (education, income, occupation), and European region. Distributions of
      reported positive, negative, and null associations were evaluated. RESULTS: A
      total of 131 studies met the inclusion criteria. Most studies were conducted in
      Scandinavia (n = 47). Leisure-time PA was the most frequently studied PA outcome
      (n = 112). Considerable differences in the direction of inequalities were seen
      for the different domains of PA. Most studies reported that those with high
      socioeconomic position were more physically active during leisure-time compared
      to those with low socioeconomic position (68% positive associations for total
      leisure-time PA, 76% for vigorous leisure-time PA). Occupational PA was more
      prevalent among the lower socioeconomic groups (63% negative associations).
      Socioeconomic differences in total PA and active transport PA did not show a
      consistent pattern (40% and 38% positive associations respectively). Some
      inequalities differed by European region or socioeconomic indicator, however
      these differences were not very pronounced. CONCLUSIONS: The direction of
      socioeconomic inequalities in PA in Europe differed considerably by domain of PA.
      The contradictory results for total PA may partly be explained by contrasting
      socioeconomic patterns for leisure-time PA and occupational PA.

PMID- 22992353
TI  - Decline in cardiorespiratory fitness and odds of incident depression.
AB  - BACKGROUND: Studies of physical activity and incidence of physician-diagnosed
      depression have been limited to a single estimate of self-reported physical
      activity exposure, despite follow-up periods lasting many years. PURPOSE: To
      examine longitudinal change in cardiorespiratory fitness, an objective marker of
      habitual physical activity, and incident depression complaints made to a
      physician. METHODS: Cardiorespiratory fitness assessed at four clinic visits
      between 1971 and 2006, each separated by an average of 2-3 years, was used to
      objectively measure cumulative physical activity exposure in cohorts of 7936 men
      and 1261 women, aged 20-85 years, from the Aerobics Center Longitudinal Study who
      did not complain of depression at their first clinic visit in 1971-2003. Data
      were analyzed in August 2010. RESULTS: Across subsequent visits, there were 446
      incident cases in men and 153 cases in women. After adjustment for age, time
      between visits, BMI at each visit, and fitness at Visit 1, each 1-minute decline
      in treadmill endurance (i.e., a decline in cardiorespiratory fitness of
      approximately 1 half-MET) between ages 51 and 55 years in men and ages 53 and 56
      years in women, increased the odds of incident depression complaints by
      approximately 2% and 9.5%, respectively. The increased odds remained significant
      but were attenuated to 1.3% and 5.4% after further adjustment at each visit for
      smoking, alcohol use, chronic medical conditions, anxiety, and sleep problems.
      CONCLUSIONS: Maintenance of cardiorespiratory fitness during late middle age,
      when decline in fitness typically accelerates, helps protect against the onset of
      depression complaints made to a physician.

PMID- 22992354
TI  - Physical activity implementation in schools: a 4-year follow-up.
AB  - BACKGROUND: Action Schools! BC (AS!BC) is a comprehensive school-based model that
      utilizes a socioecologic approach to provide children with opportunities for
      physical activity at school in British Columbia. PURPOSE: The hierarchy of
      factors associated with successful implementation of AS!BC was examined 4 years
      after it was scaled up. METHODS: A cross-sectional multistage survey was
      administered to principals (n=133; 92% response rate) and Grade 4-7 teachers
      (n=587; 71% response rate) in 2008-2009. Constructs from the theories of
      organizational change, social cognitive theory and Rogers's diffusion of
      innovation model were used to examine characteristics of teachers and schools and
      attributes of the innovation associated with implementation. Multilevel mixed
      effect logistic regression analyses were employed (analyzed in November 2011).
      RESULTS: Self-efficacy, outcome expectation, training received, organizational
      climate/support, level of institutionalization, environmental influence, and
      attributes of the innovation were associated with implementation. In multivariate
      analyses, self-efficacy, training, and level of institutionalization remained
      significant (all p<0.05). CONCLUSIONS: Demonstrating that an intervention "works"
      is only the first step toward promoting enhanced health at the population level.
      For wide-scale implementation, teacher-level self-efficacy and ongoing technical
      support to train teachers were important. At the school level, policies and
      guidelines provided a necessary, supportive environment for implementation.

PMID- 22992355
TI  - Body mass index, safety hazards, and neighborhood attractiveness.
AB  - BACKGROUND: Neighborhood attractiveness and safety may encourage physical
      activity and help individuals maintain a healthy weight. However, these
      neighborhood characteristics may not be equally relevant to health across all
      settings and population subgroups. PURPOSE: To evaluate whether potentially
      attractive neighborhood features are associated with lower BMI, whether safety
      hazards are associated with higher BMI, and whether environment-environment
      interactions are present such that associations for a particular characteristic
      are stronger in an otherwise supportive environment. METHODS: Survey data and
      measured height and weight were collected from a convenience sample of 13,102
      adult New York City (NYC) residents in 2000-2002; data analyses were completed
      2008-2012. Built-environment measures based on municipal GIS data sources were
      constructed within 1-km network buffers to assess walkable urban form (density,
      land-use mix, transit access); attractiveness (sidewalk cafes, landmark
      buildings, street trees, street cleanliness); and safety (homicide rate,
      pedestrian-auto collision and fatality rate). Generalized linear models with
      cluster-robust SEs controlled for individual and area-based sociodemographic
      characteristics. RESULTS: The presence of sidewalk cafes, density of landmark
      buildings, and density of street trees were associated with lower BMI, whereas
      the proportion of streets rated as clean was associated with higher BMI.
      Interactions were observed for sidewalk cafes with neighborhood poverty, for
      street-tree density with walkability, and for street cleanliness with safety.
      Safety hazard indicators were not independently associated with BMI. CONCLUSIONS:
      Potentially attractive community and natural features were associated with lower
      BMI among adults in NYC, and there was some evidence of effect modification.

PMID- 22992356
TI  - Smoke alarm giveaway and installation programs: an economic evaluation.
AB  - BACKGROUND: The burden of residential fire injury and death is substantial.
      Targeted smoke alarm giveaway and installation programs are popular interventions
      used to reduce residential fire mortality and morbidity. PURPOSE: To evaluate the
      cost effectiveness and cost benefit of implementing a giveaway or installation
      program in a small hypothetic community with a high risk of fire death and injury
      through a decision-analysis model. METHODS: Model inputs included program costs;
      program effectiveness (life-years and quality-adjusted life-years saved); and
      monetized program benefits (medical cost, productivity, property loss and quality
      of-life losses averted) and were identified through structured reviews of
      existing literature (done in 2011) and supplemented by expert opinion. Future
      costs and effectiveness were discounted at a rate of 3% per year. All costs were
      expressed in 2011 U.S. dollars. RESULTS: Cost-effectiveness analysis (CEA)
      resulted in an average cost-effectiveness ratio (ACER) of $51,404 per quality
      adjusted life-years (QALYs) saved and $45,630 per QALY for the giveaway and
      installation programs, respectively. Cost-benefit analysis (CBA) showed that both
      programs were associated with a positive net benefit with a benefit-cost ratio of
      2.1 and 2.3, respectively. Smoke alarm functional rate, baseline prevalence of
      functional alarms, and baseline home fire death rate were among the most
      influential factors for the CEA and CBA results. CONCLUSIONS: Both giveaway and
      installation programs have an average cost-effectiveness ratio similar to or
      lower than the median cost-effectiveness ratio reported for other interventions
      to reduce fatal injuries in homes. Although more effort is required, installation
      programs result in lower cost per outcome achieved compared with giveaways.

PMID- 22992357
TI  - Family history assessment: impact on disease risk perceptions.
AB  - BACKGROUND: Family HealthwareTM, a tool developed by the CDC, is a self
      administered web-based family history tool that assesses familial risk for six
      diseases (coronary heart disease; stroke; diabetes; and colon, breast, and
      ovarian cancers) and provides personalized prevention messages based on risk. The
      Family Healthware Impact Trial (FHITr) set out to examine the clinical utility of
      presenting personalized preventive messages tailored to family history risk for
      improving health behaviors. PURPOSE: The purpose of this study was to examine the
      impact of Family Healthware on modifying disease risk perceptions, particularly
      among those who initially underestimated their risk for certain diseases. DESIGN:
      A total of 3786 patients were enrolled in a cluster-randomized trial to evaluate
      the clinical utility of Family Healthware. SETTING/PARTICIPANTS: Participants
      were recruited from 41 primary care practices among 13 states between 2005 and
      2007. MAIN OUTCOME MEASURES: Perceived risk for each disease was assessed at
      baseline and 6-month follow-up using a single-item comparative risk question.
      Analyses were completed in March 2012. RESULTS: Compared to controls, Family
      Healthware increased risk perceptions among those who underestimated their risk
      for heart disease (15% vs 9%, p<0.005); stroke (11% vs 8%, p<0.05); diabetes (18%
      vs 11%, p<0.05); and colon cancer (17% vs 10%, p=0.05) but not breast or ovarian
      cancers. The majority of underestimators did not shift in their disease risk
      perceptions. CONCLUSIONS: Family Healthware was effective at increasing disease
      risk perceptions, particularly for metabolic conditions, among those who
      underestimated their risk. Results from this study also demonstrate the
      relatively resistant nature of risk perceptions. TRIAL REGISTRATION: This study
      is registered at clinicaltrials.govNCT00164658.

PMID- 22992358
TI  - Mailed intervention to promote sun protection of children: a randomized
      controlled trial.
AB  - BACKGROUND: Sun exposure, especially during childhood, is the most important
      preventable risk factor for skin cancer, yet few effective interventions to
      reduce exposure exist. PURPOSE: To test the effectiveness of a partially tailored
      mailed intervention based on the Precaution Adoption Process Model, delivered in
      the spring over 3 years to parents and children. DESIGN: RCT, with data
      collection through telephone interviews of parents and skin exams of children at
      baseline (Summer 2004) and annually (Summer 2005-2007). The control group
      received no intervention. SETTING/PARTICIPANTS: Families recruited in the Denver
      CO area, through private pediatric clinics, a large MCO, and community settings.
      Children born in 1998 were approximately 6 years of age at baseline; 867 children
      met inclusion criteria; analysis is reported for 677 white, non-Hispanic
      participants at highest risk for skin cancer. MAIN OUTCOME MEASURES: Primary
      outcomes were parent-reported child sun protection behaviors. Secondary outcomes
      included parents' risk perception, perceived effectiveness of and barriers to
      prevention behaviors, stage of change, reported sunburns, and observed tanning
      and nevus development. The longitudinal mixed-model analysis was conducted
      between 2008 and 2011. RESULTS: The intervention group reported more use of
      sunscreen, protective clothing, hats, shade-seeking, and midday sun avoidance;
      fewer sunburns; more awareness of the risk of skin cancer; higher perceived
      effectiveness of sun protection; higher stage of change; and lower perception of
      barriers to sun protection (all p<0.05). The intervention group had fewer nevi
      >=2 mm in 1 year of the study, 2006 (p=0.03). No differences were found in
      tanning or nevi <2 mm. CONCLUSIONS: The level of behavior change associated with
      this single-modality intervention is not likely sufficient to reduce skin cancer
      risk. However, the intervention shows promise for inclusion in longer-term,
      multicomponent interventions that have sufficient intensity to affect skin cancer
      incidence.

PMID- 22992359
TI  - Grocery store beverage choices by participants in federal food assistance and
      nutrition programs.
AB  - BACKGROUND: Sugar-sweetened beverages are a target for reduction in the 2010
      Dietary Guidelines for Americans. Concerns have been raised about sugar-sweetened
      beverages purchased with Supplemental Nutrition Assistance Program (SNAP)
      benefits. PURPOSE: This paper describes purchases of non-alcoholic refreshment
      beverages among participants in the U.S. Department of Agriculture's Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC) and SNAP.
      METHODS: Grocery store scanner data from a regional supermarket chain were used
      to assess refreshment beverage purchases of 39,172 households in January-June
      2011. The sample consisted of families with a history of WIC participation in
      2009-2011; about half also participated in SNAP. Beverage spending and volume
      purchased were compared for WIC sampled households either using SNAP benefits
      (SNAP) or not (WIC-only). Analyses were completed in 2012. RESULTS: Refreshment
      beverages were a significant contributor to expenditure on groceries by SNAP and
      WIC households. Sugar-sweetened beverages accounted for 58% of refreshment
      beverage purchases made by SNAP households and 48% of purchases by WIC-only
      households. Soft drinks were purchased most by all households. Fruit-based
      beverages were mainly 100% juice for WIC-only households and sugary fruit drinks
      for SNAP households. SNAP benefits paid for 72% of the sugar-sweetened beverage
      purchases made by SNAP households. Nationwide, SNAP was estimated to pay at least
      $1.7 to $2.1 billion annually for sugar-sweetened beverages purchased in grocery
      stores. CONCLUSIONS: Considerable amounts of sugar-sweetened beverages are
      purchased by households participating in WIC and SNAP. The SNAP program pays for
      most of the sugar-sweetened beverage purchases among SNAP households. The
      upcoming SNAP reauthorization could be a good time to reconsider the program
      priorities to align public funds with public health.

PMID- 22992360
TI  - Federal nutrition program changes and healthy food availability.
AB  - BACKGROUND: Literature on food environments is expanding rapidly, yet a gap
      exists regarding the role of the U.S. Department of Agriculture's Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC) on healthy
      food availability. In October 2009, the U.S. Department of Agriculture revised
      the WIC food package, requiring certified stores to stock fresh produce, whole
      grains, and lower-fat milk. PURPOSE: The goal of this study is to compare
      availability of foods in stores that are versus those that are not WIC-certified
      before and after the policy change. METHODS: Store inventories were collected in
      45 corner stores in Hartford CT with four inventories each (180 total
      inventories) from January 2009 to January 2010. Data on availability and variety
      of fresh fruits, fresh vegetables, whole grains, and lower-fat milk were
      recorded. Analyses were completed in 2012 using Fisher's exact test, chi-square,
      and t-tests for descriptive analyses and multilevel models to measure food
      availability longitudinally (significance at p<0.05). RESULTS: Controlling for
      covariates, WIC-certified vendors carried more varieties of fresh fruit (p<0.01);
      a greater proportion of lower-fat milk (p<0.01); and had greater availability of
      whole grain bread (p<0.01) and brown rice (p<0.05) than vendors without WIC
      authorization after the policy change. Conversely, for all outcomes, stores
      without WIC authorization did not significantly increase healthy food
      availability. CONCLUSIONS: The 2009 WIC revisions increased availability of
      healthy foods among WIC-certified vendors compared to those without WIC
      authorization in Hartford CT. For many residents without a car, these changes can
      create a convenient shopping location for healthy foods when a larger supermarket
      is not nearby.

PMID- 22992361
TI  - Fruit and vegetable availability and selection: federal food package revisions,
      2009.
AB  - BACKGROUND: With nearly 49,000 authorized retailers nationwide, a policy change
      that added fruits and vegetables (FV) to the U.S. Department of Agriculture's
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      food packages in 2009 had the potential to expand neighborhood FV availability.
      PURPOSE: This study examined changes in availability and selection of commonly
      consumed and culturally specific FV at authorized retailers (WIC vendors) before
      and after implementation of the revised WIC food packages. METHODS: Quasi
      experimental, one-group design with two pre-policy observations and one post
      policy observation. Trained observers assessed a list of fresh, frozen, and
      canned FV at each vendor in seven northern Illinois counties. Eight indices of FV
      availability and selection were derived. Multiple regression estimated
      relationships. Data were collected in 2008-2010 and analyzed in 2011. RESULTS:
      Overall, availability and selection of commonly consumed fresh FV and
      availability of African-American culturally specific fresh FV improved after
      implementation of the new policy. Modest improvements in the overall availability
      of canned low-sodium vegetables and frozen FV were observed. Changes differed by
      vendor type (large vendor, small vendor, and pharmacy). Changes in availability
      or selection did not differ by neighborhood characteristics (population density,
      median household income, racial/ethnic composition). CONCLUSIONS: Expansion of
      WIC foods was associated with small positive externalities on the food
      environment. Larger subsidies to create more demand and more-substantial stocking
      requirements for retailers may yield significantly larger improvements and thus
      warrant further investigation. Approaches targeting rural, low-income, and
      racial/ethnic minority neighborhoods also may be needed.

PMID- 22992362
TI  - Physical activity of Japanese older adults who own and walk dogs.
AB  - BACKGROUND: Dog ownership is emerging as an important correlate of sufficient
      physical activity and therefore has the potential to positively affect a portion
      of the population. A growing body of literature indicates that dog-walking
      contributes to increased physical activity. However, most of the previous studies
      have been conducted in Australia or the U.S. and have sampled from the general
      adult population. PURPOSE: This study examined the association between dog
      ownership, dog-walking, and physical activity in older Japanese adults. METHODS:
      Participants were community-dwelling residents aged 65-74 years who responded to
      a population-based cross-sectional survey (N=1926). Physical activity, dog
      ownership, dog-walking, and sociodemographic attributes were self-reported
      (collected in 2010; analyzed in 2011). ANCOVAs and multivariate logistic
      regressions were used. RESULTS: Overall, 14.0% of older adults were dog owners,
      with 71% reporting that they walked their dog for an average of 308.5+/-300.7
      minutes/week. Dog walkers reported more minutes/week of moderate-to-vigorous
      physical activity (M+/-SE: 241.7+/-27.0) and total physical activity (M+/-SE:
      698.6+/-40.6) than both non-dog walkers (M+/-SE: 110.7+/-41.8; M+/-SE: 527.2+/
      62.9) and non-dog owners (M+/-SE: 164.7+/-9.1; M+/-SE: 519.2+/-13.7),
      respectively (p<0.05). Dog walkers also walked more minutes per week (M+/-SE:
      508.0+/-33.4) than non-dog owners (M+/-SE: 384.5+/-11.3; p<0.05). Dog walkers
      were more likely to be sufficiently active than both non-dog walkers and non-dog
      owners (p<0.001). CONCLUSIONS: Use of dog-walking may be a potentially viable
      means of intervention for increasing walking and overall physical activity in
      older Japanese adults.

PMID- 22992363
TI  - Physical activity of pregnant Hispanic women.
AB  - BACKGROUND: A growing body of evidence suggests that physical activity during
      pregnancy can reduce risk of pregnancy complications. However, factors
      influencing activity in pregnant Hispanic women, who have high rates of sedentary
      activity as compared to non-Hispanic whites, are not well characterized. PURPOSE:
      To assess patterns and correlates of physical activity among 1355 participants in
      Proyecto Buena Salud, a prospective cohort of pregnant Hispanic women in
      Massachusetts from 2006 to 2011. METHODS: Analyses were conducted in 2012. Pre-,
      early-, mid-, and late-pregnancy physical activity were assessed using the
      Pregnancy Physical Activity Questionnaire. Women reported the frequency and
      duration of household/caregiving, occupational, sports/exercise, and
      transportation activities and were classified according to compliance with
      American College of Obstetricians and Gynecologists guidelines for physical
      activity. RESULTS: Household/caregiving activity was the primary mode of
      pregnancy activity ranging from 56% to 60% of total activity while
      sports/exercise contributed the least (<10%). Compared to nulliparous women,
      women with two or more children were 85% less likely to become inactive at any
      time during pregnancy (OR=0.15, 95% CI=0.04, 0.56, p-trend <0.01). Women with one
      or more children increased their total physical activity on average 9.73+/-2.04
      MET-hours/week and 12.04+/-2.39 MET-hours/week, respectively, with the onset of
      pregnancy (p<0.01). Those with the highest levels of total physical activity
      prior to pregnancy were 87% less likely to become inactive with the onset of
      pregnancy than those who were inactive prior to pregnancy (OR=0.13, 95% CI= 0.05,
      0.29). CONCLUSIONS: Findings can inform culturally appropriate interventions
      designed to reduce pregnancy complications through the promotion of physical
      activity during pregnancy.

PMID- 22992364
TI  - An interactive mapping tool to assess individual mobility patterns in
      neighborhood studies.
AB  - As their most critical limitation, neighborhood and health studies published to
      date have not taken into account nonresidential activity places where individuals
      travel in their daily lives. However, identifying low-mobility populations
      residing in low-resource environments, assessing cumulative environmental
      exposures over multiple activity places, and identifying specific activity
      locations for targeting interventions are important for health promotion. Daily
      mobility has not been given due consideration in part because of a lack of tools
      to collect locational information on activity spaces. Thus, the first aim of the
      current article is to describe VERITAS (Visualization and Evaluation of Route
      Itineraries, Travel Destinations, and Activity Spaces), an interactive web
      mapping application that can geolocate individuals' activity places, routes
      between locations, and relevant areas such as experienced or perceived
      neighborhoods. The second aim is to formalize the theoretic grounds of a
      contextual expology as a subdiscipline to better assess the spatiotemporal
      configuration of environmental exposures. Based on activity place data, various
      indicators of individual patterns of movement in space (spatial behavior) are
      described. Successive steps are outlined for elaborating variables of multiplace
      environmental exposure (collection of raw locational information,
      selection/exclusion of locational data, defining an exposure area for
      measurement, and calculation). Travel and activity place network areas are
      discussed as a relevant construct for environmental exposure assessment. Finally,
      a note of caution is provided that these measures require careful handling to
      avoid increasing the magnitude of confounding (selective daily mobility bias).

PMID- 22992365
TI  - Health behavior: a Darwinian reconceptualization.

PMID- 22992366
TI  - Carrots, sticks, or carrot sticks?: using federal food policy to engineer dietary
      change.

PMID- 22992368
TI  - Medicaid coverage of tobacco-dependence treatment for pregnant women: impact of
      the Affordable Care Act.
AB  - BACKGROUND: Twenty percent of pregnant women enrolled in Medicaid use tobacco
      products. The Affordable Care Act (ACA) requires Medicaid to cover tobacco
      dependence treatments for pregnant women beginning in 2010. PURPOSE: To summarize
      the impact of the ACA provisions on Medicaid coverage of tobacco-dependence
      treatments for pregnant women. METHODS: Medicaid programs were surveyed regarding
      their coverage for tobacco-dependence treatments after the ACA provisions went
      into effect. RESULTS: From 2009 to 2010, coverage for tobacco-dependence
      treatments increased from 43 to 51 programs covering pharmacotherapy treatments
      and from 30 to 38 programs covering tobacco-cessation counseling. States added
      additional coverage for counseling in 2011 and 2012. CONCLUSIONS: To maximize
      these benefits, Medicaid programs need to conduct outreach to inform Medicaid
      enrolled pregnant smokers of this coverage.

PMID- 22992370
TI  - Challenges in developing a skilled public health workforce: a perspective from
      London, England.

PMID- 22992369
TI  - Reporting guidelines: optimal use in preventive medicine and public health.
AB  - Numerous reporting guidelines are available to help authors write higher-quality
      papers more efficiently. Almost 200 are listed on the EQUATOR (Enhancing the
      Quality and Transparency of Health Research) Network's website and they vary in
      authority, usability, and breadth, making it difficult to decide which one(s) to
      use. This paper provides consistent information about guidelines for preventive
      medicine and public health and a framework and sequential approach for selecting
      them. The EQUATOR guidelines were reviewed for relevance to target audiences;
      selected guidelines were classified as "core" (frequently recommended) or
      specialized, and the latter were grouped by their focus. Core and specialized
      guidelines were coded for indicators of authority (simultaneous publication in
      multiple journals, rationale, scientific background supporting each element,
      expertise of designers, permanent website/named group), usability (presence of
      checklists and examples of good reporting), and breadth (article sections
      covered). Discrepancies were resolved by consensus. Selected guidelines are
      presented in four tables arranged to facilitate selection: core guidelines, all
      of which pertain to major research designs; guidelines for additional study
      designs; topical guidelines; and guidelines for particular article sections. A
      flow diagram provides an overview. The framework and sequential approach will
      enable authors as well as editors, peer reviewers, researchers, and systematic
      reviewers to make optimal use of available guidelines to improve the
      transparency, clarity, and rigor of manuscripts and research protocols and the
      efficiency in conducting systematic reviews and meta-analyses.

PMID- 22992372
TI  - Integration of ERalpha-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers
      combinatorial therapeutic opportunities to circumventing hormone resistance in
      breast cancer.
AB  - LSD1, an epigenetic modifier, and PELP1, an estrogen receptor co-activator,
      integrate estrogen receptor ERalpha and HER2 receptor tyrosine kinase signaling
      to promote aromatase expression and hormone resistance in a preclinical model of
      post-menopausal breast cancer. In the previous issue of Breast Cancer Research,
      Cortez et al. show, for the first time, that knockdown or drug-mediated
      inhibition of PELP1 or LSD1 suppresses LSD1-mediated transcriptionally activating
      histone marks at ERalpha target genes, inhibits aromatase gene expression, and
      sensitizes hormone refractory breast cancer cells to tamoxifen or letrozole
      treatments. The relevance of PELP1-LSD1 signaling to other nuclear hormone
      receptor-dependent cancers and structural considerations for the selective drug
      targeting of LSD1 are further discussed in this editorial. 

PMID- 22992373
TI  - Subfertility (Preface).

PMID- 22992374
TI  - Intracerebral delivery of carboplatin in combination with either 6 MV photons or
      monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98
      rat glioma.
AB  - BACKGROUND: The purpose of the present study was to compare side-by-side the
      therapeutic efficacy of a 6-day infusion of carboplatin, followed by X
      irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K
      edge of Pt, for treatment of F98 glioma bearing rats. METHODS: Carboplatin was
      administered intracerebrally (i.c.) to F98 glioma bearing rats over 6 days using
      AlzetTM osmotic pumps starting 7 days after tumor implantation. Radiotherapy was
      delivered in a single 15 Gy fraction on day 14 using a conventional 6 MV linear
      accelerator (LINAC) or 78.8 keV synchrotron X-rays. RESULTS: Untreated control
      animals had a median survival time (MeST) of 33 days. Animals that received
      either carboplatin alone or irradiation alone with either 78.8 keV or 6 MV had a
      MeSTs 38 and 33 days, respectively. Animals that received carboplatin in
      combination with X-irradiation had a MeST of > 180 days with a 55% cure rate,
      irrespective of whether they were irradiated with either 78.8 KeV synchrotron X
      rays or 6MV photons. CONCLUSIONS: These studies have conclusively demonstrated
      the equivalency of i.c. delivery of carboplatin in combination with X-irradiation
      with either 6 MV photons or synchrotron X-rays.

PMID- 22992375
TI  - Administration of clomipramine to neonatal mice alters stress response behavior
      and serotonergic gene expressions in adult mice.
AB  - Early life exposure to antidepressants frequently occurs when pregnant mothers
      take the medication during late pregnancy. Previous studies in animal models have
      shown that early exposure to certain antidepressants can alter some behaviors in
      adulthood. We examined whether the administration of clomipramine, a serotonin
      reuptake inhibitor, to neonatal mice could result in depression-related
      behavioral alterations in adult mice. In addition, in an attempt to uncover the
      mechanism underlying these behavioral changes, we examined the expression of
      candidate genes in different areas of the brain. Here we show that mice
      chronically injected with clomipramine specifically during early postnatal
      development demonstrated depression-like behavior as well as altered stress
      responses in adulthood. An analysis of the expression of serotonergic genes after
      exposure to social defeat stress revealed small but significant changes in the
      expression of 5-HT1A receptor gene (Htr1a) and 5-HTT gene (Slc6a4) in the mice
      treated with clomipramine compared with the mice injected with saline. We
      concluded that antidepressant exposure in early days of life could alter stress
      related behavior in adulthood and that the behavioral alterations are accompanied
      by altered serotonergic gene expressions.

PMID- 22992376
TI  - Acute effects of caffeine on attention: a comparison of non-consumers and
      withdrawn consumers.
AB  - Despite the large number of studies on caffeine and attention, interpretation is
      often difficult because of methodological weaknesses. In the present study, use
      of a small battery of tests with four key outcome measures, combined with an
      appropriate sample size, addresses many of these problems. This methodology was
      used to examine whether effects of caffeine (a dose of 2 mg/kg) could be
      explained in terms of reversal of the effects of caffeine withdrawal. This was
      achieved by examining effects in non-consumers (N = 35), who could not be
      withdrawn, and also in a group of consumers (N = 35) who had undergone withdrawal
      for a week and no longer reported symptoms of withdrawal. The results showed no
      effect of short-term withdrawal on the performance measures, even though
      subjective reports showed an increase in symptoms after withdrawal. In contrast,
      the caffeine challenge carried out on Day 8 showed that ingestion of caffeine was
      associated with faster simple reaction time, fewer long responses, greater
      detection of targets in the cognitive vigilance task, and faster encoding of new
      information. These results suggest that it is important to continue to
      investigate mechanisms underlying these effects of caffeine and to further
      evaluate the practical implications of such effects.

PMID- 22992377
TI  - Warning about side effects can increase their occurrence: an experimental model
      using placebo treatment for sleep difficulty.
AB  - Patients in clinical practice and participants in clinical trials are warned
      about side effects that may result from their treatment. Such warnings could lead
      to placebo-induced side effects if they create an expectation of these effects.
      We used an experimental model to test this possibility. Undergraduates reporting
      sleep difficulty received placebo treatment disguised as a hypnotic for one week
      and were warned about either one or four bogus side effects. Placebo treatment
      significantly improved sleep difficulty relative to a no treatment control group,
      as indicated by self-report and by objective outcomes. At the end of the
      treatment week participants who had been warned about a single side effect showed
      better recall of this effect than those warned about four side effects. Most
      importantly, participants tended to report experiencing a side effect they had
      been warned about, with a trend towards a larger effect in participants warned
      about one side effect. This evidence for placebo-induced side effects may need to
      be considered when interpreting data on side effects from clinical trials.

PMID- 22992378
TI  - Cul4B regulates neural progenitor cell growth.
AB  - BACKGROUND: Cullin ubiquitin ligases are activated via the covalent modification
      of Cullins by the small ubiquitin-like protein nedd8 in a process called
      neddylation. Genetic mutations of cullin-4b (cul4b) cause a prevalent type of X
      linked intellectual disability (XLID) in males, but the physiological function of
      Cul4B in neuronal cells remains unclear. RESULTS: There are three major isoforms
      of Cul4B (1, 2, and 3) in human and rodent tissues. By examining the endogenous
      Cul4B isoforms in the brain, this study demonstrates that Cul4B-1 and Cul4B-2
      isoforms are unneddylated and more abundant in the brain whereas the lesser
      species Cul4B-3 that misses the N-terminus present in the other two isoforms is
      neddylated. The data suggest that the N-terminus of Cul4B inhibits neddylation in
      the larger isoforms. Immunostaining of human NT-2 cells also shows that most
      Cul4B is unneddylated, especially when it is localized in the process in G0
      synchronized cells. This study demonstrates that Cul4B accumulates during mitosis
      and downregulation of Cul4B arrests NPCs and NT-2 cells in the G2/M phase of the
      cell cycle. In both human and rodent brain tissues, Cul4B-positive cells
      accumulate beta-catenin in the dentate subgranular zone and the subventricular
      zone. These Cul4B-positive cells also co-express the MPM-2 mitotic epitope,
      suggesting that Cul4B is also necessary for mitosis progression in vivo.
      CONCLUSIONS: This study provides first evidence that unneddylated Cul4B isoforms
      exist in the brain and are necessary for mitosis progression in NPCs. The data
      suggest that unneddylated Cul4B isoforms specifically inhibits beta-catenin
      degradation during mitosis. Furthermore, unneddylated Cul4B may play a role in
      addition to cell cycle since it is exclusively localized to the processes in
      starved NT-2 cells. Further analyses of the different isoforms of Cul4B will help
      understand the cognitive deficits in Cul4B-linked XLID and give insights into
      drug and biomarker discoveries.

PMID- 22992380
TI  - Anatomical MRI and DTI in the diagnosis of Alzheimer's disease: a European
      multicenter study.
AB  - Diffusion tensor imaging (DTI) detects microstructural changes of the cerebral
      white matter in Alzheimer's disease (AD). The use of DTI for the diagnosis of AD
      in a multicenter setting has not yet been investigated. We used voxel-based
      analysis of fractional anisotropy, mean diffusivity, and grey matter volumes from
      multimodal magnetic resonance imaging data of 137 AD patients and 143 healthy
      elderly controls collected across 9 different scanners. We compared different
      univariate analysis approaches to model the effect of scanner, including a linear
      model across all scans with a scanner covariate, a random effects model with
      scanner as a random variable as well as a voxel-based meta-analysis. We found
      significant reduction of fractional anisotropy and significant increase of mean
      diffusivity in core areas of AD pathology including corpus callosum, medial and
      lateral temporal lobes, as well as fornix, cingulate gyrus, precuneus, and
      prefrontal lobe white matter. Grey matter atrophy was most pronounced in medial
      and lateral temporal lobe as well as parietal and prefrontal association cortex.
      The effects of group were spatially more restricted with random effects modeling
      of scanner effects compared to simple pooled analysis. All three analysis
      approaches yielded similar accuracy of group separation in block-wise cross
      validated logistic regression. Our results suggest similar effects of center on
      group separation based on different analysis approaches and confirm a typical
      pattern of cortical and subcortical microstructural changes in AD using a large
      multimodal multicenter data set.

PMID- 22992379
TI  - Depression, suicidal ideation, and associated factors: a cross-sectional study in
      rural Haiti.
AB  - BACKGROUND: Since the 2010 earthquake in Haiti, there has been increased
      international attention to mental health needs throughout the country. The
      present study represents one of the first epidemiologic studies of depression
      symptomatology, suicidal ideation, and associated factors in Haiti's Central
      Plateau. METHODS: We conducted a cross-sectional, zone-stratified household
      survey of 408 adults in Haiti's Central Plateau. Depression symptomatology was
      assessed with a culturally-adapted Kreyol version of the Beck Depression
      Inventory (BDI). Multivariable linear and logistic regression models were built
      using backward elimination, with the outcomes being continuous BDI scores and
      endorsing suicidal ideation, respectively. RESULTS: The mean BDI score was 20.4
      (95% confidence interval [CI]: 19.3-21.5), and 6.13% (N = 25) of participants
      endorsed current suicidal ideation. Factors associated with BDI scores were:
      continuous age (adjusted beta [abeta]: 0.14, CI: 0.06-0.22), female gender
      (abeta: 2.1, CI: 0.18-4.0), suicidal ideation (abeta: 11.1, CI: 7.3-14.9), death
      in family (abeta: 2.7, CI: 0.57-4.9), and prior life-threatening illness (abeta:
      2.6, CI: 0.77-4.5). Education was a risk factor for depression among women but
      not among men, and employment was a risk factor for both genders. Factors
      associated with endorsing suicidal ideation were: BDI score (ten point change)
      (adjusted odds ratio [aOR]: 2.5, CI: 1.7-3.6), lack of care if sick (aOR: 5.5,
      CI: 1.1-28.6), alcohol use (aOR: 3.3, CI: 1.3-8.2), and ever having been to a
      Vodou priest (aOR: 3.2, CI: 1.1-9.5). CONCLUSIONS: A large proportion of Haiti's
      Central Plateau may be experiencing high levels of depression symptomatology
      and/or current suicidal ideation. Screening could be conducted in biomedical,
      religious, and Vodou healing contexts. For prevention, poverty reduction and
      improved healthcare access are key elements. For treatment, general psychiatric
      services, psychosocial services for the medically ill and their families, and
      substance abuse interventions should be explored. Paradoxical associations
      related to education and employment require further exploration.

PMID- 22992381
TI  - Immunization with live virus vaccine protects highly susceptible DBA/2J mice from
      lethal influenza A H1N1 infection.
AB  - BACKGROUND: The mouse represents an important model system to study the host
      response to influenza A infections and to evaluate new prevention or treatment
      strategies. We and others reported that the susceptibility to influenza A virus
      infections strongly varies among different inbred mouse strains. In particular,
      DBA/2J mice are highly susceptible to several influenza A subtypes, including
      human isolates and exhibit severe symptoms after infection with clinical
      isolates. FINDINGS: Upon intra-muscular immunization with live H1N1 influenza A
      virus (mouse-adapted PR8M, and 2009 pandemic human HA04), DBA/2J mice mounted
      virus-specific IgG responses and were protected against a subsequent lethal
      challenge. The immune response and rescue from death after immunization in DBA/2J
      was similar to those observed for C57BL/6J mice. CONCLUSIONS: DBA/2J mice
      represent a suitable mouse model to evaluate virulence and pathogenicity as well
      as immunization regimes against existing and newly emerging human influenza
      strains without the need for prior adaptation of the virus to the mouse.

PMID- 22992382
TI  - Sustained response to rituximab in a patient with Sjogren's syndrome and severe
      refractory polyneuropathy.

PMID- 22992383
TI  - Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and
      connective tissue is elevated in rats with collagen induced arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is a disease affecting the extracellular matrix
      of especially synovial joints. The thickness of the synovial membrane increases
      and surrounding tissue degrades, leading to altered collagen balance in the
      tissues. In this study, we investigated the altered tissue balance of cartilage,
      synovial membrane, and connective tissue in collagen induced arthritis (CIA) in
      rats. METHODS: Six newly developed ELISAs quantifying MMP-derived collagen
      degradation (C1M, C2M, and C3M) and formation (P1NP, P2NP, and P3NP) was used to
      detect cartilage turnover in rats with CIA. Moreover, CTX-II was used to detect
      alternative type II collagen degradation and as control of the model. 10 Lewis
      rats were injected with porcrine type II collagen twice with a 7 day interval and
      10 rats was injected with 0.05 M acetic acid as control. The experiment ran for
      26 days. RESULTS: A significant increase in the degradation of type I, II, and
      III collagen (C1M, C2M, and C3M, respectively) was detected on day 22 (P =
      0.0068, P = 0.0068, P < 0.0001, respectively), whereas no significant difference
      in formation (P1NP, P2NP, and P3NP) was detected at any time point (P=0.22,
      P=0.53, P=0.53, respectively). The CTX-II level increased strongly from disease
      onset and onwards. CONCLUSION: A nearly total separation between diseased and
      control animals was detected with C3M, making it a good diagnostic marker. The
      balance of type I, II, and III collagen was significantly altered with CIA in
      rats, with favour of degradation of the investigated collagens. This indicates
      unbalanced turnover of the surrounding tissues of the synovial joints, leading to
      increased pain and degeneration of the synovial joints.

PMID- 22992384
TI  - Universal access: making health systems work for women.
AB  - Universal coverage by health services is one of the core obligations that any
      legitimate government should fulfil vis-a-vis its citizens. However, universal
      coverage may not in itself ensure universal access to health care. Among the many
      challenges to ensuring universal coverage as well as access to health care are
      structural inequalities by caste, race, ethnicity and gender. Based on a review
      of published literature and applying a gender-analysis framework, this paper
      highlights ways in which the policies aimed at promoting universal coverage may
      not benefit women to the same extent as men because of gender-based differentials
      and inequalities in societies. It also explores how 'gender-blind' organisation
      and delivery of health care services may deny universal access to women even when
      universal coverage has been nominally achieved. The paper then makes
      recommendations for addressing these.

PMID- 22992385
TI  - Nitric oxide production and tolerance differ among Symbiodinium types exposed to
      heat stress.
AB  - Nitric oxide (NO) is a ubiquitous molecule and its involvement in metazoan
      microbe symbiosis is well known. Evidence suggests that it plays a role in the
      temperature-induced breakdown ('bleaching') of the ecologically important
      cnidarian-dinoflagellate association, and this can often lead to widespread
      mortality of affected hosts. This study confirms that dinoflagellates of the
      genus Symbiodinium can produce NO and that production of the compound is
      differentially regulated in different types when exposed to elevated temperature.
      Temperature-sensitive type B1 cells under heat stress (8 degrees C above ambient)
      exhibited significant increases in NO synthesis, which occurred alongside
      pronounced photoinhibition and cell mortality. Tolerant type A1 cells also
      displayed increases in NO production, yet maintained photosynthetic yields at
      levels similar to those of untreated cells and displayed less dramatic increases
      in cell death. Type C1 cells displayed a down-regulation of NO synthesis at high
      temperature, and no significant mortality increases were observed in this type.
      Temperature-induced mortality in types A1 and B1 was affected by the prevailing
      level of NO and, furthermore, photosynthetic yields of these temperature-tolerant
      and -sensitive types appeared differentially susceptible to NO donated by
      pharmacological agents. Taken together, these differences in NO synthesis and
      tolerance could potentially influence the varying bleaching responses seen among
      hosts harboring different Symbiodinium types.

PMID- 22992386
TI  - The interactions of vanadium with Phycomyces blakesleeanus mycelium: enzymatic
      reduction, transport and metabolic effects.
AB  - The biological and chemical basis of vanadium action and transport in fungi is
      relatively poorly understood. In this study we investigated the interactions of
      vanadium in physiologically-relevant redox states: vanadate (+5) and vanadyl
      (+4), with mycelium of fungus Phycomyces blakesleeanus using EPR and (31)P NMR
      spectroscopy and biochemical assays. We determined that P. blakesleeanus reduces
      V(5+) to V(4+) in the extracellular compartment by the means of cell surface
      enzyme with ferricyanide reductase activity, which contains molybdenum
      molybdopterin as a cofactor. Both, V(5+) and V(4+) bind to cell wall. They enter
      the cytoplasm via phosphate transporter and cation channels, respectively, and
      exhibit different metabolic effects. Vanadate provokes increased biomass
      production, the effects being inverted to toxic at higher V(5+) concentrations.
      In addition, V(5+) activates the synthesis of sugar phosphates and
      oligophosphates. On the other hand, V(4+) exhibits toxic effects even at low
      concentrations. The V(4+) detoxification route involves binding to vacuolar
      polyphosphates. Altogether our results imply that the mechanism of interaction of
      vanadium with P. blakesleeanus involves three major steps: extracellular
      enzymatic V(5+)/V(4+) reduction, V(4+) influx, and vacuolar storage, with an
      additional step - V(5+) import occurring at higher vanadate concentrations.

PMID- 22992388
TI  - Effect of Porphyromonas gingivalis infection on post-transcriptional regulation
      of the low-density lipoprotein receptor in mice.
AB  - BACKGROUND: Periodontal disease is suggested to increase the risk of
      atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that
      proprotein convertase subtilisin/kexin type 9 (PCSK9), which is known to play a
      critical role in the regulation of circulating low-density lipoprotein (LDL)
      cholesterol levels, is elevated in periodontitis patients. However, the
      underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely
      unknown. Here, we explored whether Porphyromonas gingivalis, a representative
      periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9
      and cholesterol levels using animal models. METHODS: We infected C57BL/6 mice
      intraperitoneally with Porphyromonas gingivalis, a representative strain of
      periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid
      profile. PCSK9 and LDL receptor (LDLR) gene and protein expression, as well as
      liver X receptors (Lxrs), inducible degrader of the LDLR (Idol), and sterol
      regulatory element binding transcription factor (Srebf)2 gene expression, were
      examined in the liver. RESULTS: P. gingivalis infection induced a significant
      elevation of serum PCSK9 levels and a concomitant elevation of total and LDL
      cholesterol compared with sham-infected mice. The LDL cholesterol levels were
      significantly correlated with PCSK9 levels. Expression of the Pcsk9, Ldlr, and
      Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice
      compared with the sham-infected mice. Although Pcsk9 gene expression is known to
      be positively regulated by sterol regulatory element binding protein (SREBP)2
      (human homologue of Srebf2), whereas Srebf2 is negatively regulated by
      cholesterol, the elevated expression of Srebf2 found in the infected mice is
      thought to be mediated by P. gingivalis infection. CONCLUSIONS: P. gingivalis
      infection upregulates PCSK9 production via upregulation of Srebf2, independent of
      cholesterol levels. Further studies are required to elucidate how infection
      regulates Srebf2 expression and subsequently influences lipid metabolism.

PMID- 22992389
TI  - Intergenerational enrollment and expenditure changes in Medicaid: trends from
      1991 to 2005.
AB  - BACKGROUND: From its inception, Medicaid was aimed at providing insurance
      coverage for low income children, elderly, and disabled. Since this time,
      children have become a smaller proportion of the US population and Medicaid has
      expanded to additional eligibility groups. We sought to evaluate relative growth
      in spending in the Medicaid program between children and adults from 1991-2005.
      We hypothesize that this shifting demographic will result in fewer resources
      being allocated to children in the Medicaid program. METHODS: We utilized
      retrospective enrollment and expenditure data for children, adults and the
      elderly from 1991 to 2005 for both Medicaid and Children's Health Insurance
      Program Medicaid expansion programs. Data were obtained from the Centers for
      Medicare and Medicaid Services using their Medicaid Statistical Information
      System. RESULTS: From 1991 to 2005, the number of enrollees increased by 83% to
      58.7 million. This includes increases of 33% for children, 100% for adults and
      50% for the elderly. Concurrently, total expenditures nationwide rose 150% to
      $273 billion. Expenditures for children increased from $23.4 to $65.7 billion,
      adults from $46.2 to $123.6 billion, and elderly from $39.2 to $71.3 billion.
      From 1999 to 2005, Medicaid spending on long-term care increased by 31% to $84.3
      billion. Expenditures on the disabled grew by 61% to $119 billion. In total, the
      disabled account for 43% and long-term care 31%, of the total Medicaid budget.
      CONCLUSION: Our study did not find an absolute decrease in the overall resources
      being directed toward children. However, increased spending on adults on a per
      capita and absolute basis, particularly disabled adults, is responsible for much
      of the growth in spending over the past 15 years. Medicaid expenditures have
      grown faster than inflation and overall national health expenditures. A national
      strategy is needed to ensure adequate coverage for Medicaid recipients while
      dealing with the ongoing constraints of state and federal budgets.

PMID- 22992387
TI  - NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary
      tumorsphere-forming activity in vitro.
AB  - INTRODUCTION: NOTCH activation has been recently implicated in human breast
      cancers, associated with a poor prognosis, and tumor-initiating cells are
      hypothesized to mediate resistance to treatment and disease relapse. To address
      the role of NOTCH1 in mammary gland development, transformation, and mammary
      tumor-initiating cell activity, we developed a doxycycline-regulated mouse model
      of NOTCH1-mediated mammary transformation. METHODS: Mammary gland development was
      analyzed by using whole-mount analysis and by flow cytometry in nulliparous
      transgenic mice maintained in the presence/absence of doxycycline (or
      intracellular NOTCH1). Mammary tumors were examined histologically and
      immunophenotyped by staining with antibodies followed by flow cytometry. Tumors
      were transplanted into mammary fat pads under limiting dilution conditions, and
      tumor-initiating cell frequency was calculated. Mammary tumor cells were also
      plated in vitro in a tumorsphere assay in the presence/absence of doxycycline.
      RNA was isolated from mammary tumor cell lines cultured in the presence/absence
      of doxycycline and used for gene-expression profiling with Affymetrix mouse
      arrays. NOTCH1-regulated genes were identified and validated by using
      quantitative real-time polymerase chain reaction (PCR). Mammary tumor-bearing
      mice were treated with doxycycline to suppress NOTCH1 expression, and disease
      recurrence was monitored. RESULTS: Similar to published studies, we show that
      constitutive expression of human intracellular NOTCH1 in the developing mouse
      mammary gland inhibits side branching and promotes luminal cell fate. These mice
      develop mammary adenocarcinomas that express cytokeratin (CK) 8/18. In vivo
      limiting-dilution analyses revealed that these mammary tumors exhibit functional
      heterogeneity and harbor a rare (1/2,978) mammary tumor-initiating cell
      population. With this dox-regulated NOTCH1 mammary tumor model, we demonstrate
      that NOTCH1 inhibition results in mammary tumor regression in vivo and prevents
      disease recurrence in four of six tumors tested. Consistent with the in vivo
      data, NOTCH1 inhibition reduces mammary tumorsphere activity in vitro. We also
      identify the embryonic stem cell transcription factor Nanog as a novel NOTCH1
      regulated gene in tumorspheres and in mouse and human breast cancer cell lines.
      CONCLUSIONS: These data indicate that NOTCH1 inhibition results in mammary tumor
      regression in vivo and interferes with disease recurrence. We demonstrate that
      NOTCH1-transformed mouse mammary tumors harbor a rare mammary tumor-initiating
      population and that NOTCH1 contributes to mammary tumor-initiating activity. This
      work raises the possibility that NOTCH therapeutics may target mammary tumor
      initiating cells in certain human breast cancer subtypes.

PMID- 22992390
TI  - Management of visual disturbances in albinism: a case report.
AB  - INTRODUCTION: A number of vision defects have been reported in association with
      albinism, such as photophobia, nystagmus and astigmatism. In many cases only
      prescription sunglasses are prescribed. In this report, the effectiveness of low
      vision rehabilitation in albinism, which included prescription of multiple visual
      aids, is discussed. CASE PRESENTATION: We present the case of a 21-year-old Asian
      woman with albinism and associated vision defects. Her problems were blurring of
      distant vision, glare and her dissatisfaction with her current auto-focus
      spectacle-mounted telescope device, which she reported as being heavy as well as
      cosmetically unacceptable. We describe how low-vision rehabilitation using
      multiple visual aids, namely spectacles, special iris-tinted contact lenses with
      clear pupils, and bi-level telemicroscopic apparatus devices improved her quality
      of life. Subsequent to rehabilitation our patient is happier and continues to use
      the visual aids. CONCLUSIONS: Contact lenses with a special iris tint and clear
      pupil area are useful aids to reduce the glare experienced by albinos. Bi-level
      telemicroscopic apparatus telemicroscopes fitted onto our patient's prescription
      spectacles were cosmetically acceptable and able to improve her distance vision.
      As a result these low-vision rehabilitation approaches improved the quality of
      life of our albino patient.

PMID- 22992391
TI  - Intervention dose estimation in health promotion programmes: a framework and a
      tool. Application to the diet and physical activity promotion PRALIMAP trial.
AB  - BACKGROUND: Although the outcomes of health promotion and prevention programmes
      may depend on the level of intervention, studies and trials often fail to take it
      into account. The objective of this work was to develop a framework within which
      to consider the implementation of interventions, and to propose a tool with which
      to measure the quantity and the quality of activities, whether planned or not,
      relevant to the intervention under investigation. The framework and the tool were
      applied to data from the diet and physical activity promotion PRALIMAP trial.
      METHODS: A framework allowing for calculation of an intervention dose in any
      health promotion programme was developed. A literature reviews revealed several
      relevant concepts that were considered in greater detail by a multidisciplinary
      working group. A method was devised with which to calculate the dose of
      intervention planned and that is actually received (programme-driven activities
      dose), as well as the amount of non-planned intervention (non-programme-driven
      activities dose). RESULTS: Indicators cover the roles of all those involved
      (supervisors, anchor personnel as receivers and providers, targets), in each
      intervention-related groups (IRG: basic setting in which a given intervention is
      planned by the programme and may differ in implementation level) and for every
      intervention period. All indicators are described according to two domains
      (delivery, participation) in two declensions (quantity and quality). Application
      to PRALIMAP data revealed important inter- and intra-IRG variability in
      intervention dose. CONCLUSIONS: A literature analysis shows that the terminology
      in this area is not yet consolidated and that research is ongoing. The present
      work provides a methodological framework by specifying concepts, by defining new
      constructs and by developing multiple information synthesis methods which must be
      introduced from the programme's conception. Application to PRALIMAP underlined
      the feasibility of measuring the implementation level. The framework and the tool
      can be used in any complex programme evaluation. The intervention doses obtained
      could be particularly useful in comparative trials. TRIAL REGISTRATION: PRALIMAP
      is registered at ClinicalTrials.gov under NCT00814554.

PMID- 22992392
TI  - Updated antibiotic resistance and clinical spectrum of infections caused by
      Streptococcus pneumoniae in Taiwan: Emphasis on risk factors for penicillin
      nonsusceptibilities.
AB  - BACKGROUND/PURPOSE(S): Streptococcus pneumoniae is one of the leading pathogens
      causing community-acquired infection with high mortality rates in elderly
      patients. Emerging antibiotic resistance was found in past decades. Continuous
      surveillance to monitor changes in antibiotic resistance of S. pneumoniae and
      associated risk factors are important clinical issues. METHODS: Isolates of S.
      pneumoniae collected from six hospitals participating in the Taiwan Surveillance
      of Antimicrobial Resistance (TSAR) program III (2002) - VI (2008) were enrolled
      in this study. Bacterial susceptibilities were determined by minimum inhibitory
      concentration. The clinical data of source patients were collected
      retrospectively. RESULTS: A total of 330 nonduplicate S. pneumoniae isolates were
      enrolled in this study. Sputum was the most common specimen source, followed by
      pus. The mean age of the source patients was 38 years among these 330 patients,
      and 247 had various infections caused by S. pneumoniae. The overall in-hospital
      mortality rate was 6% and most (60%)of the mortality occurred in patients older
      than 65 years. The mortality rates among the patients age 65 years and older and
      those age 5 years and younger were 12.9% (9 of 70) and 2.4% (2 of 83),
      respectively. The rates of nonsusceptibility to penicillin by the meningitis
      criteria (PNSP-M) were 69.0% in 2002, 81.0% in 2004, 73.7% in 2006, and 74.5% in
      2008. Resistance to erythromycin and trimethoprim/sulfamethoxazole remained high.
      Using multivariate analysis, patients with PNSP isolates were more likely to have
      a history of antibiotic exposure within the previous 15 days compared with
      patients with penicillin-susceptible (PSSP) isolates (nonmeningitis criteria:
      29.70% vs. 18.34%, p = 0.0288; meningitis criteria: 25.30% vs. 9.88%, p = 0.006).
      Shock at presentation was the risk factor for in-hospital mortality. CONCLUSION:
      Our study demonstrated that the rates of penicillin nonsusceptibility among S.
      pneumoniae remained high in Taiwan during the study period. Previous antibiotic
      exposure was the only risk factor for subsequent acquisition of penicillin-
      nonsusceptible S. pneumoniae compared with penicillin-susceptible S. pneumoniae.
      Judicious antibiotic use is important to control the spread of drug
      nonsusceptible S. pneumoniae.

PMID- 22992393
TI  - Cystic fibrosis: experience in one institution.
AB  - Cystic fibrosis (CF) is one of the most common autosomal recessive inherited
      disorders among Caucasians. Comparatively, it is considered to be a rare disease
      among Asians. To date, only a few cases of Taiwanese CF have been published. We
      report four CF cases from three families. Case 1 was the first report of CF
      associated with a homozygosity for the CF transmembrane conductance regulator
      gene (CFTR gene) mutation 3849+10kb C->T in a Taiwanese patient. Cases 2 and 3
      had heterozygous c. 1898+5 G->T and heterozygous p. I1023R (novel mutation) for
      the CFTR gene mutation. Case 4 was homozygous for the CFTR gene mutation R553X
      being reported in 2005 and complicated with cor pulmonale. These four patients
      had received 300 mg bid aerosolized tobramycin treatment every other month.

PMID- 22992394
TI  - Expression of the global regulator SATB1 is an independent factor of poor
      prognosis in high grade epithelial ovarian cancer.
AB  - BACKGROUND: The global gene regulator Special AT-rich sequence-binding protein1
      (SATB1) has been reported to reprogramme tumour cells into a more malignant
      phenotype and associate with poor clinical outcome in several cancer forms. In
      this study, we investigated the molecular correlates and prognostic impact of
      SATB1 expression in human epithelial ovarian cancer (EOC). FINDINGS:
      Immunohistochemical expression of SATB1 was examined in tissue microarrays with
      tumours from 151 incident EOC cases from two prospective, population-based
      cohorts. Benign-appearing fallopian tube epithelium from 32 cases was also
      analyzed. A multiplier of nuclear fraction and staining intensity of SATB1 was
      calculated. While barely expressed in tubal epithelium, nuclear SATB1 expression
      was denoted in 35/151 (23.2%) EOC cases. Spearman's Rho test revealed an inverse
      correlation between SATB1 expression and histological grade (R = -0.22, p =
      0.006) and a positive correlation with expression of dachshund 2 protein (R =
      0.28, p = 0.001), phosphorylated Chek1 (R = 0.26, p = 0.002) and minichromosome
      maintenance protein 3 (R = 0.17, p = 0.042). Univariable Cox regression analysis
      revealed that SATB1 expression, while not prognostic in the full cohort, was
      associated with a reduced ovarian cancer-specific survival and 5-year overall
      survival in high grade tumours (n = 105) (HR = 2.14 and HR = 1.96, respectively).
      This association remained significant in multivariable analysis, adjusted for age
      and clinical stage (HR = 2.20 and HR = 2.06, respectively). CONCLUSIONS: These
      results demonstrate that SATB1 expression is an independent factor of poor
      prognosis in high grade EOC and correlates in vivo with cellular processes
      involved in the maintenance of DNA integrity. The functional basis for these
      observations merits further investigation.

PMID- 22992395
TI  - A systematic review of the long-term outcome of early onset schizophrenia.
AB  - BACKGROUND: The current review analyzes the long-term outcome and prognosis of
      early onset schizophrenia based on previously published studies in 1980. METHODS:
      A systematic search of articles published in the English-language literature
      after 1980 identified a total of 21 studies, which included 716 patients who were
      either suffering from early onset schizophrenia (EOS) or both EOS and other
      psychotic disorders (MIX). The authors of the current review scored the outcome
      as either "good," "moderate," or "poor." The mean age of onset in these studies
      was <18 years. RESULTS: In general, the outcome in studies with EOS is worse than
      the outcome in MIX studies. Only 15.4% of the patients in EOS studies versus
      19.6% of the patients in MIX studies experienced a "good" outcome. In contrast,
      24.5% of the patients in EOS studies versus 33.6% in MIX studies experienced a
      "moderate" outcome, and 60.1% in EOS studies versus 46.8% in MIX studies
      experienced a "poor" outcome. The authors identified various significant effects
      on outcome. In EOS, the findings were significantly affected by sample attrition,
      indicating that in studies with a high dropout rate, fewer patients experienced a
      "moderate" outcome, and more patients experienced a "poor" outcome; however, the
      effect sizes were small. Furthermore, the effects were also small and more
      favourable for specific functioning measures, as opposed to more global measures,
      small to moderate in terms of worse outcomes for follow-up periods >10 years,
      small to moderate for more unfavourable outcomes in males, and small to large for
      worse outcomes in studies including patients diagnosed before 1970. CONCLUSIONS:
      In contrast to the adult manifestation, the early manifestation of schizophrenia
      in childhood and adolescence still carries a particularly poor prognosis.
      According to these aggregated data analyses, longer follow-up periods, male sex,
      and patients having been diagnosed before 1970 contribute predominantly to the
      rather poor course of EOS.

PMID- 22992396
TI  - Deciphering the differential response of two human fibroblast cell lines
      following Chikungunya virus infection.
AB  - BACKGROUND: Chikungunya virus (CHIKV) is an arthritogenic member of the
      Alphavirus genus (family Togaviridae) transmitted by Aedes mosquitoes. CHIKV is
      now known to target non hematopoietic cells such as epithelial, endothelial
      cells, fibroblasts and to less extent monocytes/macrophages. The type I
      interferon (IFN) response is an early innate immune mechanism that protects cells
      against viral infection. Cells express different pattern recognition receptors
      (including TLR7 and RIG-I) to sense viruses and to induce production of type I
      IFNs which in turn will bind to their receptor. This should result in the
      phosphorylation and translocation of STAT molecules into the nucleus to promote
      the transcription of IFN-stimulated antiviral genes (ISGs). We herein tested the
      capacity of CHIKV clinical isolate to infect two different human fibroblast cell
      lines HS 633T and HT-1080 and we analyzed the resulting type I IFN innate immune
      response. METHODS: Indirect immunofluorescence and quantitative RT-PCR were used
      to test for the susceptibility of both fibroblast cell lines to CHIKV. RESULTS:
      Interestingly, the two fibroblast cell lines HS 633T and HT-1080 were differently
      susceptible to CHIKV infection and the former producing at least 30-fold higher
      viral load at 48 h post-infection (PI). We found that the expression of antiviral
      genes (RIG-I, IFN-beta, ISG54 and ISG56) was more robust in the more susceptible
      cell line HS 633T at 48 h PI. Moreover, CHIKV was shown to similarly interfere
      with the nuclear translocation of pSTAT1 in both cell lines. CONCLUSION:
      Critically, CHIKV can control the IFN response by preventing the nuclear
      translocation of pSTAT1 in both fibroblast cell lines. Counter-intuitively, the
      relative resistance of HT-1080 cells to CHIKV infection could not be attributed
      to more robust innate IFN- and ISG-dependent antiviral responses. These cell
      lines may prove to be valuable models to screen for novel mechanisms mobilized
      differentially by fibroblasts to control CHIKV infection, replication and
      spreading from cell to cell.

PMID- 22992397
TI  - Limitations of conventional radiographs in the assessment of acetabular defects
      following total hip arthroplasty.
AB  - BACKGROUND: Conventional radiographs are routinely used to evaluate acetabular
      bone loss as part of the follow-up in patients who undergo total hip arthroplasty
      (THA). The objective of this study was to examine the accuracy and specificity of
      conventional radiographs reviewed by arthroplasty surgeons in detecting
      acetabular bone loss in patients with prior THA. METHODS: Using a cadaveric
      pelvic model, a defined percentage of bone was incrementally removed from the
      posterior acetabular column, followed by implantation of uncemented cups into
      both acetabula. Ten orthopedic arthroplasty surgeons, blinded to the defect
      sizes, assessed the percentage of bone defect using standard anteroposterior,
      Judet and oblique conventional radiographs. RESULTS: Observers were unable to
      accurately grade bone defects using conventional radiographs. For defects less
      than 50%, observers reported on average a defect of 11%. Although observer
      estimates of defects 50% or more increased, these treatment-altering bone
      deficiencies remained grossly underestimated, with a sensitivity and specificity
      of 36.6% and 97.6%, respectively. CONCLUSION: Conventional radiographs reviewed
      by experienced arthroplasty surgeons do not reliably detect small bone lesions (<
      50%). Although more successful in detecting larger bone lesions, surgeons tend to
      underestimate actual bone loss. Computed tomography scanning may be indicated if
      accurate estimation of acetabular bone loss is required in patients who have
      undergone previous THA.

PMID- 22992398
TI  - Periprosthetic osteolysis: genetics, mechanisms and potential therapeutic
      interventions.
AB  - Aseptic loosening and periprosthetic osteolysis occur as a result of the
      biological response to particulate wear debris and are one of the leading causes
      of arthroplasty failure. Periprosthetic osteolysis originates from chronic
      inflammatory responses triggered by implant-derived particulate debris, which
      cause recruitment of cells, including macrophages, fibroblasts, lymphocytes and
      osteoclasts. These cells secrete proinflammatory and osteoclastogenic cytokines,
      exacerbating the inflammatory response. In addition to their direct activation by
      phagocytosis, there are contributing autocrine and paracrine effects that create
      a complex milieu within the periprosthetic space, which ultimately governs the
      development of osteolysis. Chronic cell activation may upset the delicate balance
      between bone formation and bone resorption leading to periprosthetic osteolysis.
      This article summarizes the genetic mechanisms underlying periprosthetic
      loosening and identifies potential therapeutic agents.

PMID- 22992399
TI  - Mesenteric angiography for acute gastrointestinal bleed: predictors of active
      extravasation and outcomes.
AB  - BACKGROUND: Ongoing gastrointestinal bleeding (GIB) following endoscopic therapy
      and deciding between mesenteric angiography and surgery often challenge surgeons.
      We sought to identify predictors of positive angiographic study (active contrast
      medium extravasation) and characterize outcomes of embolization for acute GIB.
      METHODS: We retrospectively analyzed angiographies for GIB at 2 teaching
      hospitals from January 2005 to December 2008. The chi2, Wilcoxon rank sum and t
      tests determined significance. A Cox proportional hazards model was used for
      multivariate analyses. RESULTS: Eighteen of 83 (22%) patients had active
      extravasation on initial angiography and 25 (30%) were embolized. Patients with
      active extravasation had more packed red blood cell (PRBC; 5.3 v. 2.8 units, p <
      0.001) and fresh frozen plasma (4.8 v. 1.7 units, p = 0.005) transfusions 24
      hours preangiography and were more likely to be hemodynamically unstable at the
      time of the procedure (67% v. 28%, p = 0.001) than patients without active
      extravasation. Each unit of PRBC transfused increased the risk of a positive
      study by 30% (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6 per
      unit). Embolization did not decrease recurrent bleeding (53% v. 52%) or length of
      stay in hospital (28.1 v. 27.5 d, p = 0.95), but was associated with a trend
      toward fewer emergency surgical interventions (13% v. 26%, p = 0.31) and greater
      30-day mortality (33% v. 7%, p = 0.006) than nonembolization. Blind embolization
      was performed in 10 of 83 (12%) patients and was found to be an independent
      predictor of death in patients without active extravasation (HR 9.2, 95% CI 1.5
      55.9). CONCLUSION: The number of PRBC units transfused correlates with greater
      likelihood of a positive study. There was a significant increase in mortality in
      patients who underwent angioembolization. Large prospective studies are needed to
      further characterize the indications for angiography and blind embolization.

PMID- 22992400
TI  - Natural history of minimal aortic injury following blunt thoracic aortic trauma.
AB  - BACKGROUND: Endovascular repair of blunt traumatic thoracic aortic injuries
      (BTAI) is common at most trauma centres, with excellent results. However, little
      is known regarding which injuries do not require intervention. We reviewed the
      natural history of untreated patients with minimal aortic injury (MAI) at our
      centre. METHODS: We conducted a retrospective database review to identify all
      patients with a BTAI between October 2008 and March 2010. The cohort comprised
      patients initially untreated because of the lesser degree of injury of an MAI. We
      reviewed initial and follow-up computed tomography (CT) scans and clinical
      information. RESULTS: We identified 69 patients with a BTAI during the study
      period; 10 were initially untreated and were included in this study. Degree of
      injury included intimal flaps (n = 7, 70%), pseudoaneurysms with minimal hematoma
      (n = 2, 20%) and circumferential intimal tear (n = 1, 10%). Six (60%) patients
      were male, and the median age was 40 years. Duration of clinical follow-up ranged
      from 1 month to 6 years (median 2 mo) after discharge, whereas CT radiologic
      follow-up ranged from 1 week to 6 years (median 6 wk). Seven (70%) patients had
      complete resolution or stabilization of their MAI, 1 (10%) with circumferential
      intimal tear showed extension of the injury at 8 weeks postinjury and underwent
      successful repair, and 2 (20%) were lost to follow-up. CONCLUSION: There appears
      to be a subset of patients with BTAI who require no surgical intervention. This
      includes those with limited intimal flaps, which often resolve. Radiologic
      surveillance is mandatory to ensure MAI resolution and identify any progression
      that might prompt repair.

PMID- 22992401
TI  - Effect of different liver resection methods on liver damage and regeneration
      factors VEGF and FGF-2 in mice.
AB  - BACKGROUND: Different approaches to study liver regeneration in murine models
      have been proposed. We investigated the effect of different liver resection
      models on liver damage and regeneration parameters in mice. METHODS: We compared
      the technical aspect of the 2 most commonly used techniques of 50% and 70% liver
      resection. Liver damage, as determined by the change in serum alanine
      aminotransferase and aspartate aminotransferase, as well as the regeneration
      parameters VEGF and FGF-2 were analyzed at 6 time points. A postoperative
      vitality score was introduced. RESULTS: Cholestasis was not observed for either
      technique. Both resection techniques resulted in full weight recovery of the
      liver after 240 hours, with no significant difference between sham and resection
      groups. Postoperative animal morbidity and total protein levels did not differ
      significantly for either method, indicating early and full functional recovery.
      However, comparing the mitogenic growth factors FGF-2 and VEGF, a significant
      increase in serum levels and, therefore, increased growth stimulus, was shown in
      the extended resection group. CONCLUSION: Extended resection led to a greater
      response in growth factor expression. This finding is important since it shows
      that growth factor response differs acdording to the extent of resection. We have
      demonstrated the need to standardize murine hepatic resection models to
      adequately compare the resulting liver damage.

PMID- 22992402
TI  - The impact of incidental gastrointestinal stromal tumours on patients undergoing
      resection of upper gastrointestinal neoplasms.
AB  - BACKGROUND: Emerging data suggest asymptomatic gastrointestinal stromal tumours
      (GISTs) of the upper gastrointestinal (UGI) tract are not uncommon. We sought to
      determine their incidence in patients undergoing resection for UGI neoplasms and
      their impact on surgical and adjuvant treatment. METHODS: We accessed a database
      prospectively listing all patients undergoing resection of non-GIST neoplasms of
      the stomach and esophagus at a single university centre over a 4.5-year period
      and reviewed pathology reports for the presence of synchronous GISTs in the UGI
      tract. We compared patient demographic and tumour characteristics, operative
      procedures and postoperative outcomes. RESULTS: In all, 207 patients undergoing
      gastrectomy or esophagectomy for non- GIST neoplasms were included. We identified
      15 synchronous GISTs in the UGI tract of 11 (5.3%) patients (1 preoperatively, 4
      intraoperatively and 10 on final pathology), with an average age of 67 years.
      Most patients were men. Additional resections were required for GISTs identified
      pre- or intraoperatively. Final pathology revealed completely resected c-kit
      positive tumours of an average size of 0.5 (range 0.1-4.0) cm with low or very
      low risk of malignant potential. No patients received adjuvant therapy for the
      GISTs. After a median follow-up of 11 (range 2-36) months, 5 patients died from
      their primary cancer, 3 were alive with primary cancer recurrence, and 3 were
      alive without disease. No patients experienced GIST recurrence. CONCLUSION:
      Incidentally finding a synchronous GIST during resection of UGI neoplasms is not
      uncommon; it may alter surgical treatment but is unlikely to impact longterm
      survival.

PMID- 22992403
TI  - Total hip arthroplasty in steroid-induced osteonecrosis: early functional and
      radiological outcomes.
AB  - BACKGROUND: The proportion of total hip arhtoplasties (THAs) associated with
      corticosteroid use is uncertain, and the mechanisms of corticosteroid-induced
      osteonecrosis remain unknown. We sought to evaluate the clinical and radiographic
      outcomes, complications and satisfaction with THA among patients with
      corticosteroid-induced osteonecrosis. METHODS: We retrospectively assessed
      functional outcome at a minimum 1-year follow-up using the Western Ontario and
      MacMaster Universities Arthritis Index (WOMAC); Oxford Hip Score; Short Form (SF)
      12; University of California, Los Angeles (UCLA) Activity; and patient
      satisfaction scores. RESULTS: We included 31 patients (35 hips). The average
      follow-up was 20 (range 12- 55) months, and the average age at surgery was 47
      (range 19-78) years. At follow-up, patients showed significant improvement in all
      4 components of the WOMAC (means: function 84, stiffness 75, pain 86, global 84),
      Oxford-12 (mean 83) and SF-12 (means: mental 40 and physical 48) scores. However,
      there was no significant improvement in the UCLA Activity scores. Mean patient
      satisfaction scores were good for pain relief (86), function (80), recreation
      (77.5) and overall results of surgery (86). Radiographic review at follow-up
      showed that all components were well fixed with no evidence of loosening. The
      complication rate was high (17%), with 6 complications in 5 patients (6 of 35
      hips). Four patients (4 of 35 hips; 11%) required reoperations. CONCLUSION: Total
      hip arthroplasty in patients with corticosteroid-induced osteonecrosis of the
      femoral head is successful in reducing pain and improving function; however, the
      rate of complications and reoperation is high.

PMID- 22992404
TI  - Periprosthetic joint infections at a teaching hospital in 1990-2007.
AB  - BACKGROUND: Periprosthetic joint infections (PJIs) are major complications
      associated with high costs and substantial morbidity. We sought to evaluate hip
      and knee arthroplasty infection rates at our hospital, compare them in periods
      before and after implementation of measures to reduce PJIs (1990-2002 and 2003
      2007) and identify associated risk factors. METHODS: We retrospectively reviewed
      records of patients who received primary hip or knee total joint prostheses at
      our centre between Jan. 1, 1990, and Dec. 31, 2007, and were readmitted for the
      treatment of infection related to their surgery. We also reviewed data from a
      prospective surveillance protocol of total hip (THA) and knee arthroplasty (TKA)
      infections that started in November 2005. We ascertained the annual rates of
      deep, superficial and hematogenous infections. RESULTS: During the periods
      studied, 2403 THAs and 1220 TKAs were performed. For THA, the average rates of
      deep, superficial and hematogenous infections were 2.0%, 0.8% and 0.3%,
      respectively. For TKA, the rates were 1.6%, 0.7% and 0.2%, respectively. Of 106
      infected joints, 84 (79.2%) presented risk factors for infection. Efforts to
      reduce the infection rate at our institution began in 2003. We achieved a 44%
      decrease in the deep infection rate for THA (2.5% v. 1.4%; p = 0.06) and a 45%
      decrease for TKA (2.0% v. 1.1%, p = 0.20) between the periods studied.
      CONCLUSION: Knowing the actual infection rate associated with different
      procedures in specific settings is essential to identify unexpected problems and
      seek solutions to improve patient care. Although we do not know what specific
      improvements were successful, we were able to decrease our infection rates to
      levels comparable to those reported by similar care centres.

PMID- 22992405
TI  - Altered processing of emotional stimuli in migraine: an event-related potential
      study.
AB  - BACKGROUND: Migraine patients report psychosocial stress to be among the major
      triggers for their migraine attacks. The mechanisms underlying the onset of
      migraine attacks are not yet fully understood. Neuroimaging studies have shown
      changes in the cortical excitability of migraine patients. Here, we investigated
      cortical activation related to processing of emotional stimuli in individuals
      with migraine. METHOD: Twenty-four participants suffering from migraine attacks
      and 25 healthy volunteers had to passively observe pictures of emotional facial
      expressions (angry, happy and neutral). Electro-cortical activity was
      continuously recorded by means of an electroencephalogram (EEG), and ratings of
      valence (unpleasant vs. pleasant) and arousal (calm vs. exciting) were collected.
      RESULTS: The migraine and control group did not differ in their ratings of
      valence and arousal of the visual stimuli. However, participants with migraine,
      in contrast to healthy controls, showed larger N170 amplitudes toward angry
      facial expressions compared to neutral ones. DISCUSSION: Individuals with
      migraine may have an altered cortical activity linked to the processing of
      emotional information. Thus, these individuals may process high arousing and
      threatening events preferentially, and this facilitated processing may be related
      to their already high cortical excitability.

PMID- 22992406
TI  - Atrial septal defect closure and de novo migraine: Exclusive ticlopidine
      efficacy.
AB  - BACKGROUND: De novo onset or aggravation of migraine has been observed after
      atrial septal defect closure (ASDC), whereas antiplatelet drugs, such as
      clopidogrel, used to prevent post-ASDC thromboembolic events, have been
      associated with migraine amelioration. CASE: We report the case of a woman who,
      after ASDC, experienced de novo severe migraine with aura. Whereas use of
      acetylsalicylic acid or clopidogrel had no effect, ticlopidine use was associated
      with migraine amelioration. Migraine relapsed after two ticlopidine dechallenges,
      and disappeared after drug rechallenges. CONCLUSION: A ticlopidine trial could be
      proposed to patients with migraine which occurs or worsens immediately after ASDC
      and does not improve with clopidogrel.

PMID- 22992407
TI  - Rac2 expression and its role in neutrophil functions of zebrafish (Danio rerio).
AB  - The neutrophil contributes significantly to the immune response. In particular,
      their phagocytosis and pathogen-killing functions are vital for defense from
      invading pathogens. Rac2, a Rho small GTPase, is involved in many key neutrophil
      functions. Loss of Rac2 activity results in severe bacterial infections and
      neutrophil function deficits in humans and mice. While the genes rac1, 2, and 3
      have been identified in the zebrafish genome, their expression has not been well
      characterized. We describe rac1, 2, and 3 expression over the first three days of
      development, as well as the presence and localization of Rac2 protein in adult
      zebrafish neutrophils. The mRNA for each Rac isoform was detected in zebrafish
      embryos as early as 12 h post fertilization. Immunocytochemistry and confocal
      microscopy of adult zebrafish neutrophils confirmed diffuse Rac2 protein within
      the cytoplasm. Only rac2 was found in sorted neutrophil samples. Armed with
      knowledge of its presence and exclusive expression, the role of Rac2 in key
      antimicrobial zebrafish neutrophil responses was examined by small molecule
      inhibition of Rac during respiratory burst, NET release, and phagocytosis assays.
      Inhibition of Rac2 during these assays produced a dose-dependent decrease in each
      function, as was expected due to previous work in mammals. The expression pattern
      and role of Rac2 in zebrafish neutrophil function allows for comparative studies
      of innate immune responses in this animal model.

PMID- 22992408
TI  - Therapeutic efficacy of CXCR3 blockade in an experimental model of severe sepsis.
AB  - INTRODUCTION: In our previous studies we demonstrated that CXC chemokine receptor
      3 (CXCR3) participates in the regulation of lymphocyte trafficking during cecal
      ligation and puncture (CLP)-induced sepsis. In this study, we evaluated the
      effects of treatment with anti-CXCR3 immunoglobulin (IgG) and antibiotics on
      outcome during septic shock caused by CLP. METHODS: C57BL/6J mice were treated
      with neutralizing IgG against CXCR3 plus Primaxin either 24 hours prior to, 2
      hours after or 6 hours after CLP. Control mice received nonspecific IgG plus
      Primaxin in the same regimen. Survival, core body temperature, bacterial
      clearance and systemic cytokine production were evaluated. RESULTS: Our results
      show that treatment with anti-CXCR3 IgG plus Primaxin significantly improved
      survival when administered 24 hours prior to CLP (50% vs. 10%), 2 hours after CLP
      (55% vs. 10%) or 6 hours after CLP (55% vs. 25%) compared with mice receiving
      nonspecific IgG plus Primaxin. Treatment with anti-CXCR3 plus Primaxin 24 hours
      prior to CLP attenuated hypothermia and IL-6 and macrophage inflammatory protein
      2 (MIP-2) production but did not alter bacterial clearance. Treatment with anti
      CXCR3 IgG and Primaxin 2 hours after CLP did not improve bacterial clearance and
      systemic cytokine production compared with mice treated with IgG and Primaxin,
      whereas 6 hours after CLP the bacterial clearance and IL-6 and MIP-2
      concentrations, both in plasma and peritoneal lavage fluid, were significantly
      improved in mice receiving anti-CXCR3 IgG and Primaxin compared with mice that
      only received nonspecific IgG and Primaxin. CONCLUSION: The results from this
      study indicate that neutralization of CXCR3 prior to, 2 hours after or 6 hours
      after the initiation of CLP-induced septic shock improves survival and attenuates
      CLP-induced inflammation and physiologic dysfunction.

PMID- 22992410
TI  - The role of insurance in the achievement of universal coverage within a
      developing country context: South Africa as a case study.
AB  - BACKGROUND: Achieving universal coverage as an objective needs to confront the
      reality of multiple mechanisms, with healthcare financing and provision occurring
      in both public and private settings. South Africa has both large and mature
      public and private health systems offering useful insights into how they can be
      effectively harmonized to optimise coverage. Private healthcare in South Africa
      has also gone through many phases and regulatory regimes which, through careful
      review, can help identify potential policy frameworks that can optimise their
      ability to deepen coverage in a manner that complements the basic coverage of
      public arrangements. RESEARCH QUESTION: Using South Africa as a case study, this
      review examines whether private health systems are susceptible to regulation and
      therefore able to support an extension and deepening of coverage when
      complementing a pre-existing publicly funded and delivered health system?
      METHODS: The approach involves a review of different stages in the development of
      the South African private health system and its response to policy changes. The
      focus is on the time-bound characteristics of the health system and associated
      policy responses and opportunities. A distinction is consequently made between
      the early, largely unregulated, phases of development and more mature phases with
      alternative regulatory regimes. RESULTS: The private health system in South
      Africa has played an important supplementary role in achieving universal coverage
      throughout its history, but more especially in the post-Apartheid period.
      However, the quality of this role has been erratic, influenced predominantly by
      policy vacillation.The private system expanded rapidly during the 1980s mainly
      due to the pre-existence of a mature health insurance system and a weakening
      public hospital system which could accommodate and facilitate an increased demand
      for private hospital services. This growth served to expand commercial interest
      in health insurance, in the form of regulated medical schemes, which until this
      point took the form of non-commercial occupational (employer-based) schemes.
      During the 1980s government acquiesced to industry lobbies arguing for the
      deregulation of health insurance from 1989, with an extreme deregulation
      occurring in 1994, evidently in anticipation of the change of government
      associated with the democratic dispensation. Dramatic unintended consequences
      followed, with substantial increases in provider and funder costs coinciding with
      uncontrolled discrimination against poor health risks.Against significant
      industry opposition, including legal challenges, partial re-regulation took
      effect from 2000 which removed the discretion of schemes to discriminate against
      poor health risks. This included: the implementation of a strong regulator of
      health insurance; the establishment of one allowable vehicle able to provide
      health insurance; open enrolment, whereby schemes could not refuse membership
      applications; mandatory minimum benefit requirements; and a prohibition on
      setting contributions or premiums on the basis of health status. After a two-year
      lag, dramatically reduced cost trends and contributions became evident. Aside
      from generally tighter regulation across a range of fronts, this appears related
      to the need for schemes to compete more on the basis of healthcare provider costs
      than demographic risk profiles. Despite an incomplete reform improved equitable
      coverage and cost-containment was nevertheless achieved.A more complete
      regulatory regime is consequently likely to deepen coverage by: further
      stabilising and even decreasing costs; enhanced risk pooling; and access for low
      income groups. This would occur if South Africa: improved the quality of free
      public services, thereby creating competitive constraints for medical schemes;
      introduced risk-equalisation, increasing the pressure on schemes to compete on
      the cost and quality of coverage rather than their risk profile; and through the
      establishment of improved price regulation. CONCLUSIONS: The objective of
      universal coverage can be seen in two dimensions, horizontal extension and
      vertical deepening. Private systems play an important role in deepening coverage
      by mobilising revenue from income earners for health services over-and-above the
      horizontal extension role of public systems and related subsidies. South Africa
      provides an example of how this natural deepening occurs whether regulated or
      unregulated. It also demonstrates how poor regulation of mature private systems
      can severely undermine this role and diminish achievements below attainable
      levels of social protection. The mature South African system has demonstrated its
      sensitivity to regulatory design and responds rapidly to changes both positive
      and negative. When measures to enhance risk pooling are introduced, coverage is
      expanded and becomes increasingly fair and sustainable. When removed, however,
      the system becomes less stable and fair as costs rise and people with poor health
      status are systematically excluded from cover. This susceptibility to regulation
      therefore presents an opportunity to policymakers to achieve social protection
      objectives through the strategic management of markets rather than exclusively
      through less responsive systems based on tax-funded direct provision. This is
      especially relevant as private markets for healthcare are inevitable, with policy
      discretion reduced to a choice between functional or dysfunctional regimes.

PMID- 22992409
TI  - Care of undocumented-uninsured immigrants in a large urban dialysis unit.
AB  - BACKGROUND: Medical, ethical and financial dilemmas may arise in treating
      undocumented-uninsured patients with end-stage renal disease (ESRD). Hereby we
      describe the 10-year experience of treating undocumented-uninsured ESRD patients
      in a large public dialysis-unit. METHODS: We evaluated the medical files of all
      the chronic dialysis patients treated at the Tel-Aviv Medical Center between the
      years 2000-2010. Data for all immigrant patients without documentation and
      medical insurance were obtained. Clinical data were compared with an age-matched
      cohort of 77 insured dialysis patients. RESULTS: Fifteen undocumented-uninsured
      patients were treated with chronic scheduled dialysis therapy for a mean length
      of 2.3 years and a total of 4953 hemodialysis sessions, despite lack of
      reimbursement. All undocumented-uninsured patients presented initially with
      symptoms attributed to uremia and with stage 5 chronic kidney disease (CKD). In
      comparison, in the age-matched cohort, only 6 patients (8%) were initially
      evaluated by a nephrologist at stage 5 CKD. Levels of hemoglobin (8.5 +/- 1.7
      versus 10.8 +/- 1.6 g/dL; p < 0.0001) and albumin (33.8 +/- 4.8 versus 37.7 +/-
      3.9 g/L; p < 0.001) were lower in the undocumented-uninsured dialysis patients
      compared with the age-matched insured patients at initiation of hemodialysis
      therapy. These significant changes were persistent throughout the treatment
      period. Hemodialysis was performed in all the undocumented-uninsured patients via
      tunneled cuffed catheters (TCC) without higher rates of TCC-associated
      infections. The rate of skipped hemodialysis sessions was similar in the
      undocumented-uninsured and age-matched insured cohorts. CONCLUSIONS: Undocumented
      uninsured dialysis patients presented initially in the advanced stages of CKD
      with lower levels of hemoglobin and worse nutritional status in comparison with
      age-matched insured patients. The type of vascular access for hemodialysis was
      less than optimal with regards to current guidelines. There is a need for the
      national and international nephrology communities to establish a policy
      concerning the treatment of undocumented-uninsured patients with CKD.

PMID- 22992411
TI  - Design and rationale of the MR-INFORM study: stress perfusion cardiovascular
      magnetic resonance imaging to guide the management of patients with stable
      coronary artery disease.
AB  - BACKGROUND: In patients with stable coronary artery disease (CAD), decisions
      regarding revascularisation are primarily driven by the severity and extent of
      coronary luminal stenoses as determined by invasive coronary angiography. More
      recently, revascularisation decisions based on invasive fractional flow reserve
      (FFR) have shown improved event free survival. Cardiovascular magnetic resonance
      (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion
      imaging in a multi-centre setting and superior in a single centre trial. In
      addition, it is similar to invasively determined FFR and therefore has the
      potential to become the non-invasive test of choice to determine need for
      revascularisation. TRIAL DESIGN: The MR-INFORM study is a prospective, multi
      centre, randomised controlled non-inferiority, outcome trial. The objective is to
      compare the efficacy of two investigative strategies for the management of
      patients with suspected CAD. Patients presenting with stable angina are
      randomised into two groups: 1) The FFR-INFORMED group has subsequent management
      decisions guided by coronary angiography and fractional flow reserve
      measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion
      CMR. The primary end-point will be the occurrence of major adverse cardiac events
      (death, myocardial infarction and repeat revascularisation) at one year. Clinical
      trials.gov identifier NCT01236807. CONCLUSION: MR INFORM will assess whether an
      initial strategy of CMR perfusion is non-inferior to invasive angiography
      supplemented by FFR measurements to guide the management of patients with stable
      coronary artery disease. Non-inferiority of CMR perfusion imaging to the current
      invasive reference standard (FFR) would establish CMR perfusion imaging as an
      attractive non-invasive alternative to current diagnostic pathways.

PMID- 22992412
TI  - Evaluation of right and left ventricular function using speckle tracking
      echocardiography in patients with arrhythmogenic right ventricular cardiomyopathy
      and their first degree relatives.
AB  - INTRODUCTION AND AIM: The identification of right ventricular abnormalities in
      patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) in early
      stages is still difficult. The aim of this study was to investigate if
      longitudinal strain based on speckle tracking can detect subtle right (RV) or
      left ventricular (LV) dysfunction as an early sign of ARVC. METHODS AND RESULTS:
      Seventeen male patients, fulfilling Task force criteria for ARVC, 49 (32-70)
      years old, nineteen male first degree relatives 29 (19-73) y.o. and twenty-two
      healthy male volunteers 36 (24-66) y.o participated in the study. Twelve-lead and
      signal-averaged electrocardiograms were recorded. All subjects underwent
      echocardiography. LV and RV diameters, peak systolic velocity from tissue Doppler
      and longitudinal strain based on speckle tracking were measured from the basal
      and mid segments in both ventricles. RV longitudinal strain measurement was
      successful in first degree relatives and controls (95 resp. 86%) but less
      feasible in patients (59%). Results were not systematically different between
      first degree relatives and controls. Using discriminant analysis, we then
      developed an index based on echocardiographic parameters. All normal controls had
      an index<l while patients with abnormal ventricles had an index between 1-4. Some
      of the first degree relatives deviated from the normal pattern. CONCLUSION:
      Longitudinal strain of LV and RV segments was significantly lower in patients
      than in relatives and controls. An index was developed incorporating dimensional
      and functional echocardiographic parameters. In combination with genetic testing
      this index might help to detect early phenotype expression in mutation carriers.

PMID- 22992413
TI  - Assistive technology use and human rights enjoyment: a cross-sectional study in
      Bangladesh.
AB  - BACKGROUND: About half a billion people with disabilities in developing
      countries have limited access to assistive technology. The Convention on the
      Rights of persons with Disabilities requires governments to take measures to
      ensure provision of such technologies. To guide implementation of these measures
      there is a need for understanding health outcomes from a human rights
      perspective. The objective of this study was therefore to explore the relation
      between assistive technology use and enjoyment of human rights in a low-income
      country. METHODS: Data was collected in eight districts of Bangladesh through
      interviews of people with hearing impairments using and not using hearings aids,
      and people with ambulatory impairments using and not using manual wheelchairs (N
      = 583). Using logistic regression, self-reported outcomes on standard of living,
      health, education, work, receiving information and movement were analyzed.
      RESULTS: The adjusted likelihood of reporting greater enjoyment of human rights
      was significantly higher among people using hearing aids compared to non-users
      for all outcomes except working status. Compared to non-users, users of
      wheelchairs reported a significantly higher adjusted likelihood of good
      ambulatory performance and a significantly lower adjusted likelihood of reporting
      a positive working status. Further analyses indicated that physical accessibility
      to working places and duration of wheelchair use had a statistically significant
      impact on the likelihood of reporting positive work outcomes. CONCLUSIONS: The
      findings support the notion that assistive technology use increases the
      likelihood of human rights enjoyment, particularly hearing aid use. Physical
      accessibility should always be addressed in wheelchair provision.

PMID- 22992414
TI  - Adipose tissue dysregulation and reduced insulin sensitivity in non-obese
      individuals with enlarged abdominal adipose cells.
AB  - BACKGROUND: Obesity contributes to Type 2 diabetes by promoting systemic insulin
      resistance. Obesity causes features of metabolic dysfunction in the adipose
      tissue that may contribute to later impairments of insulin action in skeletal
      muscle and liver; these include reduced insulin-stimulated glucose transport,
      reduced expression of GLUT4, altered expression of adipokines, and adipocyte
      hypertrophy. Animal studies have shown that expansion of adipose tissue alone is
      not sufficient to cause systemic insulin resistance in the absence of adipose
      tissue metabolic dysfunction. To determine if this holds true for humans, we
      studied the relationship between insulin resistance and markers of adipose tissue
      dysfunction in non-obese individuals. METHOD: 32 non-obese first-degree relatives
      of Type 2 diabetic patients were recruited. Glucose tolerance was determined by
      an oral glucose tolerance test and insulin sensitivity was measured with the
      hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and
      subcutaneous abdominal adipose tissue biopsies obtained for gene/protein
      expression and adipocyte cell size measurements. RESULTS: Our findings show that
      also in non-obese individuals low insulin sensitivity is associated with signs of
      adipose tissue metabolic dysfunction characterized by low expression of GLUT4,
      altered adipokine profile and enlarged adipocyte cell size. In this group,
      insulin sensitivity is positively correlated to GLUT4 mRNA (R = 0.49, p = 0.011)
      and protein (R = 0.51, p = 0.004) expression, as well as with circulating
      adiponectin levels (R = 0.46, 0 = 0.009). In addition, insulin sensitivity is
      inversely correlated to circulating RBP4 (R = -0.61, 0 = 0.003) and adipocyte
      cell size (R = -0.40, p = 0.022). Furthermore, these features are inter
      correlated and also associated with other clinical features of the metabolic
      syndrome in the absence of obesity. No association could be found between the
      hypertrophy-associated adipocyte dysregulation and HIF-1alpha in this group of
      non-obese individuals. CONCLUSIONS: In conclusion, these findings support the
      concept that it is not obesity per se, but rather metabolic dysfunction of
      adipose tissue that is associated with systemic insulin resistance and the
      metabolic syndrome.

PMID- 22992415
TI  - A crisis resolution and home treatment team in Norway: a longitudinal survey
      study Part 1. Patient characteristics at admission and referral.
AB  - BACKGROUND: Crisis resolution and home treatment (CRHT) is an emerging mode of
      delivering acute mental health care in the community. There is a paucity of
      knowledge regarding the workings of CRHT in the literature. This is the first
      paper in a series of three from the longitudinal survey of patients of a CRHT
      team in Norway, which was aimed at describing the characteristics of patients
      served, professional services provided, and clinical outcomes. This report
      focuses on describing the characteristics of the patients at admission. METHODS:
      The study was a descriptive, quantitative study based on the patient data from a
      longitudinal survey of one CRHT team in Norway. The participants of the survey, a
      total of 363 patients, were the complete registration of patients of this team in
      the period from February 2008 to July 2009. RESULTS: Although diverse in their
      characteristics, the patients were over represented by females, young to middle
      aged, and people on public support. The patients were mostly referred to the team
      by self/family members and primary care physicians. At admission, depression was
      the most prevalent symptom, the overall intensity level of mental health problems
      was low, and most of the patients had long-standing mental health problems.
      CONCLUSIONS: Self/family referral seems to be a critical route to receive
      services by CRTH teams as shown in our study, suggesting a need to examine
      policies that disallow this form of referral in some communities. The findings
      from our study show that the patients of the CRHT team, while mostly having long
      standing mental health problems and had been receiving healthcare for them, did
      not have severe mental health problems at admission, although could have been in
      crises. There is a need for further studies to examine how people with severe
      mental health problems obtain services in time of crises, and to address the need
      to gain a greater understanding of the role of CRHT.

PMID- 22992416
TI  - Attenuation of Zn-induced hyperleptinemia/leptin resistance in Wistar rat after
      feeding modified poultry egg.
AB  - BACKGROUND: The prevalence of obesity is increasing exponentially world over.
      Leptin resistance/hyperleptinemia is attributed to its cause in majority of the
      obese humans where mutation in genetic component or ob gene has not been found
      operative. The generation of oxidative stress was suggested as its cause. In our
      previous study, we have reported that the inclusion of antioxidant enriched
      modified poultry egg (ME) in diet reversed the ionic imbalance and ameliorated
      the oxidative stress caused by excessive Zn in diet. In the present study, the
      efficacy of ME verses conventional egg (CE) was tested on Zn-induced leptin
      resistance in rat model to ascertain if the supplementation of antioxidants in
      the form of egg can reverse Zn-induced leptin resistance to leptin sensitive
      state. METHODS: Hyperleptinemia was induced in rats by feeding them Zn
      supplemented hyperleptinemic diets-I and II (Zn-HL-Diet) for 2 months.
      Thereafter, half of them were fed either on CE or ME mixed Zn-HL-diets I and II
      for another two months. The data was analyzed applying one way Anova and Tukey's
      HSD post hoc test. RESULTS: The results revealed that food intake, gain in body
      weight, height and number/unit surface area of intestinal microvillus and serum
      leptin, glucose, insulin and cortisol were higher in CE and Zn-HL-Diet treated
      groups; serum Zn, Cu, Mg were higher and Cu and Mg in tissues were lower in them
      than the control group. In ME treated groups, these parameters were lower and
      were close to the control group. These changes resulted from the restoration of
      ionic balance of Zn, Cu and Mg in the blood serum and tissues including liver and
      hair in ME treated rats. CONCLUSION: The data suggest that Zn-induced leptin
      resistance can be attenuated through restoring the ionic balance of Zn, Cu and Mg
      through inclusion of antioxidants in diet such as these modified eggs. But
      further clinical studies are required before they are put to use for human
      consumption.

PMID- 22992417
TI  - Implementation salvage experiences from the Melbourne diabetes prevention study.
AB  - BACKGROUND: Many public health interventions based on apparently sound evidence
      from randomised controlled trials encounter difficulties when being scaled up
      within health systems. Even under the best of circumstances, implementation is
      exceedingly difficult. In this paper we will describe the implementation salvage
      experiences from the Melbourne Diabetes Prevention Study, which is a randomised
      controlled trial of the effectiveness and cost-effectiveness nested in the state
      wide Life! Taking Action on Diabetes program in Victoria, Australia. DISCUSSION:
      The Melbourne Diabetes Prevention Study sits within an evolving larger scale
      implementation project, the Life! program. Changes that occurred during the roll
      out of that program had a direct impact on the process of conducting this trial.
      The issues and methods of recovery the study team encountered were conceptualised
      using an implementation salvage strategies framework. The specific issues the
      study team came across included continuity of the state funding for Life! program
      and structural changes to the Life! program which consisted of adjustments to
      eligibility criteria, referral processes, structure and content, as well as
      alternative program delivery for different population groups. Staff turnover,
      recruitment problems, setting and venue concerns, availability of potential
      participants and participant characteristics were also identified as evaluation
      roadblocks. Each issue and corresponding salvage strategy is presented. SUMMARY:
      The experiences of conducting such a novel trial as the preliminary Melbourne
      Diabetes Prevention Study have been invaluable. The lessons learnt and knowledge
      gained will inform the future execution of this trial in the coming years. We
      anticipate that these results will also be beneficial to other researchers
      conducting similar trials in the public health field. We recommend that
      researchers openly share their experiences, barriers and challenges when
      conducting randomised controlled trials and implementation research. We encourage
      them to describe the factors that may have inhibited or enhanced the desired
      outcomes so that the academic community can learn and expand the research
      foundation of implementation salvage.

PMID- 22992418
TI  - Suppression of metastases of small cell lung cancer cells in mice by a peptidic
      CXCR4 inhibitor TF14016.
AB  - CXCL12 is a chemokine essential for the organ-specific spread of a variety of
      cancers including small cell lung cancer (SCLC). Here, we examined the anti
      metastatic efficacy of TF14016, a small peptidic inhibitor of CXCL12 receptor
      CXCR4, in SCLC. Treatment of mice with TF14016 significantly suppressed pulmonary
      metastases of CXCR4-expressing SCLC in size and number. Furthermore, histological
      examination revealed that the expression of vascular endothelial cell growth
      factor and the density of CD31-positive microvessels in metastatic foci were both
      significantly reduced in TF14016-treated mice. Collectively, CXCR4 could be an
      attractive target for anti-metastatic and anti-angiogenic therapy in SCLC.

PMID- 22992419
TI  - Is Ontario medicine asleep at the switch?

PMID- 22992421
TI  - Elective and emergency abdominal surgery in patients 90 years of age or older.
AB  - BACKGROUND: Few studies have examined perioperative outcomes in nonagenarians
      undergoing abdominal surgery, and fewer have reported on 1-year mortality. Our
      objectives were to determine the outcomes of abdominal surgery in nonagenarians
      and to assess the performance of Physiologic and Operative Severity Score for
      enUmeration of Mortality and morbidity (POSSUM) and Portsmouth-POSSUM (p- POSSUM)
      as predictors of mortality. METHODS: We conducted a retrospective chart review of
      all patients 90 years and older who underwent abdominal surgery between 2000 and
      2007 at a tertiary care hospital. RESULTS: We included 145 patients (median age
      91, range 90-101 yr). The most common diagnoses were colorectal cancer (19.3%)
      and hernias (19.3%), and the most common procedures were bowel resection with
      anastomosis (25.5%) and hernia repair (18.6%). Overall in-hospital mortality was
      15.2% (20.8% in the emergent group and 9.6% in the elective group; p = 0.06). The
      1-year mortality (49.1% v. 27.8%; p = 0.016), complication (81.9% v. 61.6%; p =
      0.007) and intensive care unit admission rates (44.4% v. 11.0%; p < 0.001) were
      significantly higher among emergent than elective surgical patients. The
      operative indications and procedures associated with the highest in-hospital
      mortality were large bowel obstruction (42.3%) and bowel resection with
      anastomosis (27.0%). Both the POSSUM and p-POSSUM scoring systems significantly
      overpredicted mortality, particularly in higher risk groups. CONCLUSION:
      Nonagenarians undergoing abdominal surgery have substantial operative morbidity
      and mortality, particularly in emergent surgical cases. Nearly 50% of patients
      who undergo emergency procedures die within 1 year after surgery. The POSSUM and
      p-POSSUM scoring systems were not reliable predictors of in-hospital mortality.

PMID- 22992422
TI  - CAGS and ACS evidence based reviews in surgery. Risks of complications by
      attending physicians after performing nighttime procedures.

PMID- 22992424
TI  - Breast lumpectomy margins.

PMID- 22992425
TI  - Joseph Lister: father of modern surgery.

PMID- 22992426
TI  - Exploring family communication about sickle cell disease in adolescence.
AB  - Sickle cell disease (SCD) is a lifelong disorder that involves progressive organ
      damage and requires ongoing medical attention to prevent and treat episodic acute
      complications. Children with SCD need ongoing monitoring and extra attention that
      may be stressful to family members. Communication within families can help
      resolve family stress and may be associated with medical follow-up and management
      of SCD. Focus groups were conducted with 12 African American families to explore
      the communication that occurred within and outside of the family from the
      perspectives of adolescents with SCD, siblings, and parents. Factors that
      influence family communication were explored. The extended family was an
      important social network and resource to adolescents, siblings, and parents.
      Family member knowledge of SCD was an important factor that influenced
      communication about SCD; adolescents and parents communicated more easily than
      siblings and also reported having more knowledge of SCD than siblings. Future
      research focusing on the knowledge of immediate and extended family members and
      their recognition of their contribution to the child with SCD is recommended.

PMID- 22992427
TI  - Parental decision making for children with cancer at the end of life: a meta
      ethnography.
AB  - Parents of pediatric oncology patients are faced with difficult decisions when
      their child reaches the end of life. For health care providers to provide optimal
      care, they must understand parents' perspectives and preferences in end-of-life
      decision making. Therefore, this article provides a systematic review of the
      literature on the end-of-life decision making of parents of children with cancer
      as well as recommendations for practice and future research. Parents participated
      in surveys, focus groups, participant observation, and interviews to help
      researchers understand the expectations, hopes, fears, and values that guide
      their decision making. Common themes were patient-provider communication,
      extending time, and understanding prognosis.

PMID- 22992428
TI  - The feasibility, perceived satisfaction, and value of using synchronous webinars
      to educate clinical research professionals on reporting adverse events in
      clinical trials: a report from the Children's Oncology Group.
AB  - Clinical research professionals are faced with decreased funding and increased
      workloads; innovative methods of professional development programs are necessary
      to accommodate these factors. This study evaluated the feasibility, perceived
      satisfaction, and value of using webinars to educate clinical research
      professionals on reporting adverse events commonly experienced in pediatric
      oncology clinical trials. The setting incorporated synchronous web-based
      educational technology. Constructivist learning provides the theoretical
      framework for this study. Participants evaluated the professional development
      program at 2 time points: (a) at the conclusion and (b) 4 to 6 weeks afterward,
      using survey method. Synchronous webinars were both economical and effective in
      educating clinical research professionals across institutional sites.
      Participants reported exceptionally high levels of satisfaction with the
      accessibility, scope, quality, and interactivity of the professional development
      program. The vast majority of participants reported that the education would
      assist with reporting adverse events in pediatric oncology clinical trials and
      this perception persisted into clinical practice. Although the results of this
      study were intended to guide future educational efforts of the Children's
      Oncology Group, they may also apply to other cooperative groups.

PMID- 22992430
TI  - The effect of a cold beverage during an exercise session combining both strength
      and energy systems development training on core temperature and markers of
      performance.
AB  - BACKGROUND: Although studies have investigated the effects of hydration on
      performance measures, few studies have investigated how the temperature of the
      ingested liquid affects performance and core temperature during an exercise
      session. The hypothesis of the present study was that cold water would improve
      thermoregulation and performance as measured by bench repetitions to fatigue,
      broad jump for force and power and total time to exhaustion for cardiovascular
      fitness METHODS: Forty-five, physically fit, adult males (30.28 +/- 5.4 yr, 1.77
      +/- 7.8 m, 83.46 +/- 11.5 kg; 13.7 +/- 4.8 %BF; 49.8 +/- 6.3 ml/kg/min V02)
      completed two 60-minute exercise sessions. Subjects consumed either COLD (4
      degrees C) or room temperature (RT) water (22 degrees C) in randomized order.
      Core temperature was measured every 15 minutes throughout each trial using a
      digestible thermometer. Three performance tests were performed upon completion of
      the exercise session: bench press to fatigue, standing broad jump, and bicycle
      time to exhaustion RESULTS: Although both groups significantly increased their
      core temperature (p<0.001) over the course of the exercise session and presented
      a significant decline in hydration status (p<0.001), participants in the COLD
      water trial had a significantly (p=0.024) smaller rise in core temperature (0.83
      degrees ) over the duration of the trial in comparison to RT (1.13 degrees ). The
      participants in the COLD water trial were able to delay their increase in core
      body temperature for at least 30 minutes, whereas participants in the RT trial
      increased body temperature from baseline after 15 minutes. There was no
      significant difference between the COLD or the RT trials in broad jump and TTE
      performance tests. Bench press showed a small, albeit significant (p=0.046),
      decrease in performance when drinking COLD CONCLUSION: Drinking cold water can
      significantly mediate and delay the increase in core body temperature during an
      exercise session in a moderate climate with euhydrated subjects. The ingestion of
      COLD improved performance for 49% and 51% of the participants in the broad jump
      and TTE performance tests respectively, but did not reach statistical
      significance. Moreover, although minimal, subjects experienced a decrease in
      performance on the bench press during the COLD.

PMID- 22992429
TI  - alpha-Lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima
      Fatty rats.
AB  - BACKGROUND: Hyperglycemia leads to cardiac oxidative stress and an imbalance in
      glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac
      hypertrophy and fibrosis. However, the underlying mechanisms of diabetic
      cardiomyopathy are not fully understood. This study aimed to investigate the
      effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant
      effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF)
      rats. METHODS: Animals were separated into non-diabetic Long-Evans Tokushima
      Otsuka (LETO) rats and diabetes-prone OLETF rats with or without ALA (200
      mg/kg/day) administration for 16 weeks. Diabetic cardiomyopathy was assessed by
      staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant
      enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by
      Western blot analysis or immunohistochemistry. RESULTS: Western blot analysis
      showed that cardiac adenosine monophosphate-activated kinase (AMPK) signalling
      was lower in OLETF rats than in LETO rats, and that ALA treatment increased the
      signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats
      was increased by ALA treatment. In addition to increased Sirius red staining of
      collagen deposits, transforming growth factor-beta1 (TGF-beta1) and connective
      tissue growth factor (CTGF) were expressed at higher levels in OLETF rat hearts
      than in LETO rat hearts, and the levels of these factors were decreased by ALA.
      CONCLUSIONS: ALA enhances AMPK signalling, antioxidant, and antifibrogenic
      effect. Theses findings suggest that ALA may have beneficial effects in the
      treatment of diabetic cardiomyopathy.

PMID- 22992431
TI  - Why has the Universal Coverage Scheme in Thailand achieved a pro-poor public
      subsidy for health care?
AB  - BACKGROUND: Thailand has achieved universal health coverage since 2002 through
      the implementation of the Universal Coverage Scheme (UCS) for 47 million of the
      population who were neither private sector employees nor government employees. A
      well performing UCS should achieve health equity goals in terms of health service
      use and distribution of government subsidy on health. With these goals in mind,
      this paper assesses the magnitude and trend of government health budget
      benefiting the poor as compared to the rich UCS members. METHOD: Benefit
      incidence analysis was conducted using the nationally representative household
      surveys, Health and Welfare Surveys, between 2003 and 2009. UCS members are
      grouped into five different socio-economic status using asset indexes and wealth
      quintiles. FINDINGS: The total government subsidy, net of direct household
      payment, for combined outpatient (OP) and inpatient (IP) services to public
      hospitals and health facilities provided to UCS members, had increased from 30
      billion Baht (US$ 1 billion) in 2003 to 40-46 billion Baht in 2004-2009. In 2003
      for 23% and 12% of the UCS members who belonged to the poorest and richest
      quintiles of the whole-country populations respectively, the share of public
      subsidies for OP service was 28% and 7% for the poorest and the richest
      quintiles, whereby for IP services the share was 27% and 6% for the poorest and
      richest quintiles respectively. This reflects a pro-poor outcome of public
      subsidies to healthcare. The OP and IP public subsidies remained consistently pro
      poor in subsequent years.The pro-poor benefit incidence is determined by higher
      utilization by the poorest than the richest quintiles, especially at health
      centres and district hospitals. Thus the probability and the amount of household
      direct health payment for public facilities by the poorest UCS members were less
      than their richest counterparts. CONCLUSIONS: Higher utilization and better
      financial risk protection benefiting the poor UCS members are the results of
      extensive geographical coverage of health service infrastructure especially at
      district level, adequate finance and functioning primary healthcare,
      comprehensive benefit package and zero copayment at points of services.

PMID- 22992432
TI  - The assessment of generalized anxiety disorder: psychometric validation of the
      Spanish version of the self-administered GAD-2 scale in daily medical practice.
AB  - AIM: To psychometrically validate the Spanish version of the self-administered 2
      item GAD-2 scale for screening probable patients with generalised anxiety
      disorder (GAD). METHODS: The GAD-2 was self-administered by patients diagnosed
      with GAD according to DSM-IV criteria and by age- and sex-matched controls who
      were recruited at random in mental health and primary care centres. Criteria
      validity was explored using ROC curve analysis, and sensitivity, specificity and
      positive and negative predictive values were determined for different cut-off
      values. Concurrent validity was also established using the HAM-A, HADS, and
      WHODAS II scales. RESULTS: The study sample consisted of 212 subjects (106
      patients with GAD) with a mean age of 50.38 years (SD = 16.76). No items of the
      scale were left blank. Floor and ceiling effects were negligible. No patients
      with GAD had to be assisted to complete the questionnaire. Reliability (internal
      consistency) was high; Cronbach's alpha = 0.875. A cut-off point of 3 showed
      adequate sensitivity (91.5%) and specificity (85.8%), with a statistically
      significant area under the curve (AUC = 0.937, p < 0.001), to distinguish GAD
      patients from controls. Concurrent validity was also high and significant with
      HAM-A (0.806, p < 0.001), HADS (anxiety domain, 0.825, p < 0.001) and WHO-DAS II
      (0.642, p < 0.001) scales. CONCLUSION: The Spanish version of the GAD-2 scale has
      been shown to have appropriate psychometric properties to rapidly detect probable
      cases of GAD in the Spanish cultural context under routine clinical practice
      conditions.

PMID- 22992433
TI  - Engineering Escherichia coli to increase plasmid DNA production in high cell
      density cultivations in batch mode.
AB  - BACKGROUND: Plasmid DNA (pDNA) is a promising molecule for therapeutic
      applications. pDNA is produced by Escherichia coli in high cell-density
      cultivations (HCDC) using fed-batch mode. The typical limitations of such
      cultivations, including metabolic deviations like aerobic acetate production due
      to the existence of substrate gradients in large-scale bioreactors, remain as
      serious challenges for fast and effective pDNA production. We have previously
      demonstrated that the substitution of the phosphotransferase system by the over
      expressed galactose permease for glucose uptake in E. coli (strain VH33) allows
      efficient growth, while strongly decreases acetate production. In the present
      work, additional genetic modifications were made to VH33 to further improve pDNA
      production. Several genes were deleted from strain VH33: the recA, deoR, nupG and
      endA genes were inactivated independently and in combination. The performance of
      the mutant strains was evaluated in shake flasks for the production of a 6.1 kb
      plasmid bearing an antigen gene against mumps. The best producer strain was
      cultivated in lab-scale bioreactors using 100 g/L of glucose to achieve HCDC in
      batch mode. For comparison, the widely used commercial strain DH5alpha, carrying
      the same plasmid, was also cultivated under the same conditions. RESULTS: The
      various mutations tested had different effects on the specific growth rate,
      glucose uptake rate, and pDNA yields (YP/X). The triple mutant VH33 Delta (recA
      deoR nupG) accumulated low amounts of acetate and resulted in the best YP/X (4.22
      mg/g), whereas YP/X of strain VH33 only reached 1.16 mg/g. When cultivated at
      high glucose concentrations, the triple mutant strain produced 186 mg/L of pDNA,
      40 g/L of biomass and only 2.2 g/L of acetate. In contrast, DH5alpha produced
      only 70 mg/L of pDNA and accumulated 9.5 g/L of acetate. Furthermore, the
      supercoiled fraction of the pDNA produced by the triple mutant was nearly
      constant throughout the cultivation. CONCLUSION: The pDNA concentration obtained
      with the engineered strain VH33 Delta (recA deoR nupG) is, to the best of our
      knowledge, the highest reported for a batch cultivation, and its supercoiled
      fraction remained close to 80%. Strain VH33 Delta (recA deoR nupG) and its
      cultivation using elevated glucose concentrations represent an attractive
      technology for fast and efficient pDNA production and a valuable alternative to
      fed-batch cultivations of commercial strains.

PMID- 22992434
TI  - Screening and genetic manipulation of green organisms for establishment of
      biological life support systems in space.
AB  - Curiosity has driven humankind to explore and conquer space. However, today,
      space research is not a means to relieve this curiosity anymore, but instead has
      turned into a need. To support the crew in distant expeditions, supplies should
      either be delivered from the Earth, or prepared for short durations through
      physiochemical methods aboard the space station. Thus, research continues to
      devise reliable regenerative systems. Biological life support systems may be the
      only answer to human autonomy in outposts beyond Earth. For construction of an
      artificial extraterrestrial ecosystem, it is necessary to search for highly
      adaptable super-organisms capable of growth in harsh space environments. Indeed,
      a number of organisms have been proposed for cultivation in space. Meanwhile,
      some manipulations can be done to increase their photosynthetic potential and
      stress tolerance. Genetic manipulation and screening of plants, microalgae and
      cyanobacteria is currently a fascinating topic in space bioengineering. In this
      commentary, we will provide a viewpoint on the realities, limitations and
      promises in designing biological life support system based on engineered and/or
      selected green organism. Special focus will be devoted to the engineering of key
      photosynthetic enzymes in pioneer green organisms and their potential use in
      establishment of transgenic photobioreactors in space.

PMID- 22992435
TI  - Health and education: service providers in partnership to improve mental health.
AB  - BACKGROUND: Children and adolescents from complex or disadvantaged backgrounds
      and multiple needs often are reluctant to seek help and this is particularly
      relevant in the context of mental health difficulties. Further, the complexity of
      the health system can be overwhelming to the family who are likely to be chaotic
      and less able to seek help. The current project piloted an integrated service
      delivery model involving a child psychiatry service and the department of
      education to promote access to mental health assessment and intervention to young
      people attending special education schools in Sydney, Australia. FINDINGS AND
      CONCLUSION: The project allowed improved access to mental health services for a
      group of young people who would otherwise not have sought help through
      traditional referral pathways. Our findings support strategies to promote the
      social milieu of schools as a way of achieving better mental health and learning
      outcomes.

PMID- 22992436
TI  - Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute
      renal failure after treatment of JBP485 in rats.
AB  - The purpose of this study is to investigate whether the effect of cyclo-trans-4-l
      hydroxyprolyl-l-serine (JBP485) on acute renal failure (ARF) induced by cisplatin
      is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485
      reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma
      and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate
      (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats.
      The plasma concentration of PAH (para-aminohippurate) determined by LC-MS/MS was
      increased markedly after intravenous administration of cisplatin, whereas
      cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were
      significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and
      protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin
      treated rats, and an increase in IS (a uremic toxin) after co-treatment with
      JBP485. It indicated that JBP485 promoted urinary excretion of toxins by
      upregulating renal Mrp2. This therefore gives in part the explanation about the
      mechanism by which JBP485 improves ARF induced by cisplatin in rats.

PMID- 22992437
TI  - Probiotic supplementation affects markers of intestinal barrier, oxidation, and
      inflammation in trained men; a randomized, double-blinded, placebo-controlled
      trial.
AB  - BACKGROUND: Probiotics are an upcoming group of nutraceuticals claiming positive
      effects on athlete's gut health, redox biology and immunity but there is lack of
      evidence to support these statements. METHODS: We conducted a randomized, double
      blinded, placebo controlled trial to observe effects of probiotic supplementation
      on markers of intestinal barrier, oxidation and inflammation, at rest and after
      intense exercise. 23 trained men received multi-species probiotics (1010 CFU/day,
      Ecologic(r)Performance or OMNi-BiOTiC(r)POWER, n = 11) or placebo (n = 12) for 14
      weeks and performed an intense cycle ergometry over 90 minutes at baseline and
      after 14 weeks. Zonulin and alpha1-antitrypsin were measured from feces to
      estimate gut leakage at baseline and at the end of treatment. Venous blood was
      collected at baseline and after 14 weeks, before and immediately post exercise,
      to determine carbonyl proteins (CP), malondialdehyde (MDA), total oxidation
      status of lipids (TOS), tumor necrosis factor-alpha (TNF-alpha), and interleukin
      6 (IL-6). Statistical analysis used multifactorial analysis of variance (ANOVA).
      Level of significance was set at p < 0.05, a trend at p < 0.1. RESULTS: Zonulin
      decreased with supplementation from values slightly above normal into normal
      ranges (<30 ng/ml) and was significantly lower after 14 weeks with probiotics
      compared to placebo (p = 0.019). We observed no influence on alpha1-antitrypsin
      (p > 0.1). CP increased significantly from pre to post exercise in both groups at
      baseline and in the placebo group after 14 weeks of treatment (p = 0.006). After
      14 weeks, CP concentrations were tendentially lower with probiotics (p = 0.061).
      TOS was slightly increased above normal in both groups, at baseline and after 14
      weeks of treatment. There was no effect of supplementation or exercise on TOS. At
      baseline, both groups showed considerably higher TNF-alpha concentrations than
      normal. After 14 weeks TNF-alpha was tendentially lower in the supplemented group
      (p = 0.054). IL-6 increased significantly from pre to post exercise in both
      groups (p = 0.001), but supplementation had no effect. MDA was not influenced,
      neither by supplementation nor by exercise. CONCLUSIONS: The probiotic treatment
      decreased Zonulin in feces, a marker indicating enhanced gut permeability.
      Moreover, probiotic supplementation beneficially affected TNF-alpha and exercise
      induced protein oxidation. These results demonstrate promising benefits for
      probiotic use in trained men. CLINICAL TRIAL REGISTRY:
      http://www.clinicaltrials.gov, identifier: NCT01474629.

PMID- 22992439
TI  - Transcription levels of sirtuin family in neural stem cells and brain tissues of
      adult mice.
AB  - Neural stem cells (NSCs) has been used as a well-known model to investigate
      apoptosis, differentiation, maintenance of stem cells status, and therapy of
      neurological disease. The C17.2 NSCs line was produced after v-myc transformation
      of neural progenitor from mouse cerebellar cortex. Sirtuin family plays important
      roles involved in neuronal differentiation, genomic stability, lifespan, cell
      survival. However, little is known about gene expression variation of sirtuin
      family in C17.2 NSCs, primary NSCs, and different brain tissues in adult mice.
      Here, we confirmed that the mRNA expression levels of sirt2, 3, 4, 5, and 7 in
      E14.5 NSCs were significantly higher than in C17.2 NSCs, whereas that sirt 6
      displayed an opposing mode. Moreover, a higher mRNA level of sirtuin family was
      observed in the adult mouse brain compared to C17.2 NSCs. In addition, histone
      deacetylase (HDAC) inhibitors nicotinamide and Trichostatin A (TSA) were used to
      explore differential changes at the transcriptional level of sirtuins. Results
      indicated that the expression of sirt1, sirt5 and sirt6 was significant
      downregulated by nicotinamide treatment. Whereas, a significant downregulation in
      sirt1 and sirt3 and a significant upregulation in sirt2, sirt4, sirt6, and sirt7
      were observed in the treatment of TSA. Thus our studies indicate different
      sirtuin mRNA expression profiles between C17.2 NSCs, E14.5 NSCs and brain
      tissues, suggesting the transcriptional regulation of sirtuin family could be
      mediated by different histone acetylation.

PMID- 22992438
TI  - Relationship between the physical environment and different domains of physical
      activity in European adults: a systematic review.
AB  - BACKGROUND: In the past decade, various reviews described the relationship
      between the physical environment and different physical activity (PA) domains.
      Yet, the majority of the current review evidence relies on North
      American/Australian studies, while only a small proportion of findings refer to
      European studies. Given some clear environmental differences across continents,
      this raises questions about the applicability of those results in European
      settings. This systematic review aimed at summarizing Europe-specific evidence on
      the relationship between the physical environment and different PA domains in
      adults. METHODS: Seventy eligible papers were identified through systematic
      searches across six electronic databases. Included papers were observational
      studies assessing the relationship between several aspects of the physical
      environment and PA in European adults (18-65y). Summary scores were calculated to
      express the strength of the relationship between each environmental factor and
      different PA domains. RESULTS: Convincing evidence on positive relationships with
      several PA domains was found for following environmental factors: walkability,
      access to shops/services/work and the composite factor environmental quality.
      Convincing evidence considering urbanization degree showed contradictory results,
      dependent on the observed PA domain. Transportation PA was more frequently
      related to the physical environment than recreational PA. Possible evidence for a
      positive relationship with transportation PA emerged for walking/cycling
      facilities, while a negative relationship was found for hilliness. Some
      environmental factors, such as access to recreational facilities, aesthetics,
      traffic- and crime-related safety were unrelated to different PA domains in
      Europe. CONCLUSIONS: Generally, findings from this review of European studies are
      in accordance with results from North American/Australian reviews and may
      contribute to a generalization of the relationship between the physical
      environment and PA. Nevertheless, the lack of associations found regarding access
      to recreational facilities, aesthetics and different forms of safety are likely
      to be Europe-specific findings and need to be considered when appropriate
      interventions are developed. More research assessing domain-specific
      relationships with several understudied environmental attributes (e.g.,
      residential density) is needed.

PMID- 22992440
TI  - Epigenetic alterations of adenomatous polyposis coli (APC), retinoic acid
      receptor beta (RARbeta) and survivin genes in tumor tissues and voided urine of
      bladder cancer patients.
AB  - The CpG promoter methylation has been reported to occur frequently in bladder
      cancer. Moreover, analysis of gene methylation has been shown to be feasible from
      voided urine and can be detected with a high degree of sensitivity. The aim of
      this present study is to determine how methylation patterns of APC, RAR&#946; and
      Survivin genes change during bladder carcinogenesis and to evaluate whether DNA
      methylation could be detected in urine sediment. Using the sensitive assay of
      MSP, we explored the promoter methylation status for the three genes in tumor
      specimens and urine sediment DNA from 32 bladder cancer patients. Methylation
      frequencies of the tested genes in tumor specimens were 100%, 75% and 84.4% for
      APC, RAR&#946; and Survivin, respectively. Hypermethylation of APC was found in
      all pathological grades and stages of bladder cancer. More frequent promoter
      hypermethylation of RAR&#946; and Survivin was observed in high grade tumors and
      the hypermethylation increased from low to high stages, but there was no
      significant correlation between stages/grades and hypermethylation of these two
      gene promoters. In order to investigate clinical usefulness for noninvasive
      bladder cancer detection, we further analyzed the methylation status in urine
      samples of bladder cancer patients. Methylation of the tested genes in urine
      sediment DNA was detected in the majority of cases that were hypermethylated in
      tumor samples (93.7%) and the frequencies were 79.3% 70.8% and 96.3% for APC,
      RAR&#946; and Survivin, respectively. Our results indicate that methylation of
      APC, RAR&#946; and Survivin gene promoters is a common finding in patients with
      bladder carcinoma. The ability to detect methylation not only in bladder tissue,
      but also in urine sediments, suggests that methylation markers are promising
      tools for noninvasive detection of bladder cancer.

PMID- 22992441
TI  - Effect of water temperature increase on HO-1 expression in European sea bass
      (Dicentrarchus labrax L.) tissues.
AB  - One of the most pertinent environmental factors influencing the marine organism
      life is temperature. It has been demonstrated that an increase of temperature is
      able to induce the synthesis of heat shock proteins (HSP). In this study we
      investigated the expression of HO-1 mRNA, also referred to as HSP32, in different
      tissues of European sea bass (Dicentrarchus labrax, L.) at several time points
      after increased temperature exposure (from 12degC to 30degC). Our results showed
      that HO-1 was not expressed in gills, heart, muscle and brain while it was
      expressed at a basal level in intestine. In liver, spleen and kidneys, HO-1
      expression was influenced by temperature increases. In the spleen, we found a
      significant decrease of the HO-1 expression at the end of 4 weeks. In kidneys a
      very fast collapse of HO-1 expression level was recorded reaching null value as
      soon as one hour after exposure to 30degC. In liver, HO-1 expression increased
      from one hour of exposure to 30degC confirming HO-1 involvement to heat shock
      response in this organ. This increasing trend reached a 4.5-fold higher value
      than the initial level after 4 weeks.

PMID- 22992442
TI  - Hyper IgM syndrome presenting as chronic suppurative lung disease.
AB  - The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic
      disorders resulting in defects of immunoglobulin class switch recombination.
      Affected patients show humoral immunodeficiency and high susceptibility to
      opportunistic infections. Elevated serum IgM levels are the hallmark of the
      disease, even though in few rare cases they may be in the normal range. Hyper IgM
      is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some
      cases, alterations in different genes may be identified. Mutations in five genes
      have so far been associated to the disease, which can be inherited with an X
      linked (CD40 ligand, and nuclear factor-kB essential modulator defects) or an
      autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA
      glycosylase mutation) pattern. The patient herein described presented with
      recurrent upper and lower respiratory infections and evidence of suppurative lung
      disease at the conventional chest imaging. The presence of low serum IgG and IgA
      levels, elevated IgM levels, and a marked reduction of in vivo switched memory B
      cells led to a clinical and functional diagnosis of HIGM although the genetic
      cause was not identified.

PMID- 22992443
TI  - Advancing the evidence base in cancer: psychosocial multicenter trials.
AB  - BACKGROUND: The diagnosis and treatment of cancer is associated with significant
      distress and psychosocial morbidity. Although psychosocial interventions have
      been developed in an attempt to improve psychosocial outcomes in cancer patients
      and survivors, there is continued debate about whether there is adequate high
      level evidence to establish the effectiveness of these interventions. The
      evidence base is limited as a result of numerous challenges faced by those
      attempting to conduct psychosocial intervention trials within the health system.
      Barriers include insufficient participant recruitment, difficulty generalizing
      from single-trial studies, difficulty in building and managing research teams
      with multidisciplinary expertise, lack of research design expertise and a lack of
      incentives for researchers conducting intervention research. To strengthen the
      evidence base, more intervention studies employing methodologically rigorous
      research designs are necessary. METHODS: In order to advance the evidence base of
      interventions designed to improve psychosocial outcomes for cancer patients and
      survivors, we propose the formation of a collaborative trials group that conducts
      multicenter trials to test the effectiveness of such interventions. RESULTS:
      Establishment of such a group would improve the quality of the evidence base in
      psychosocial research in cancer patients, by increasing support for conducting
      intervention research and providing intervention research training opportunities.
      A multidisciplinary collaborative group conducting multicenter trials would have
      the capacity to overcome many of the barriers that currently exist. CONCLUSIONS:
      A stronger evidence base is necessary to identify effective psychosocial
      interventions for cancer patients. The proposed formation of a psycho-oncology
      collaborative trials group that conducts multicenter trials to test the
      effectiveness of psychosocial interventions would assist in achieving this
      outcome.

PMID- 22992444
TI  - Financing universal coverage in Malaysia: a case study.
AB  - One of the challenges to maintain an agenda for universal coverage and equitable
      health system is to develop effective structuring and management of health
      financing. Global experiences with different systems of health financing suggests
      that a strong public role in health financing is essential for health systems to
      protect the poor and health systems with the strongest state role are likely the
      more equitable and achieve better aggregate health outcomes. Using Malaysia as a
      case study, this paper seeks to evaluate the progress and capacity of a middle
      income country in terms of health financing for universal coverage, and also to
      highlight some of the key underlying health systems challenges.The WHO Health
      Financing Strategy for the Asia Pacific Region (2010-2015) was used as the
      framework to evaluate the Malaysian healthcare financing system in terms of the
      provision of universal coverage for the population, and the Malaysian National
      Health Accounts (2008) provided the latest Malaysian data on health spending.
      Measuring against the four target indicators outlined, Malaysia fared credibly
      with total health expenditure close to 5% of its GDP (4.75%), out-of-pocket
      payment below 40% of total health expenditure (30.7%), comprehensive social
      safety nets for vulnerable populations, and a tax-based financing system that
      fundamentally poses as a national risk-pooled scheme for the
      population.Nonetheless, within a holistic systems framework, the financing
      component interacts synergistically with other health system spheres. In
      Malaysia, outmigration of public health workers particularly specialist doctors
      remains an issue and financing strategies critically needs to incorporate a
      comprehensive workforce compensation strategy to improve the health workforce
      skill mix. Health expenditure information is systematically collated, but
      feedback from the private sector remains a challenge. Service delivery-wise,
      there is a need to enhance financing capacity to expand preventive care, in
      better managing escalating healthcare costs associated with the increasing trend
      of non-communicable diseases. In tandem, health financing policies need to infuse
      the element of cost-effectiveness to better manage the purchasing of new medical
      supplies and equipment. Ultimately, good governance and leadership are needed to
      ensure adequate public spending on health and maintain the focus on the
      attainment of universal coverage, as well as making healthcare financing more
      accountable to the public, particularly in regards to inefficiencies and better
      utilisation of public funds and resources.

PMID- 22992445
TI  - How "proficient" is proficient? comparison of English and relative proficiency
      rating as a predictor of bilingual listeners' word recognition.
AB  - PURPOSE: The current study attempted to validate that English proficiency self
      ratings predict bilinguals' recognition of English words as reported in Shi
      (2011) and to explore whether relative proficiency ratings (English vs. first
      language) improve prediction. METHOD: One hundred and twenty-four participants in
      Shi (2011) and an additional set of 145 participants were included (Groups 1 and
      2, respectively) in this study. All listeners rated their proficiency in
      listening, speaking, and reading (English and first language) on an 11-point
      scale and listened to a list of words from the Northwestern University Auditory
      Tests No. 6 (Tillman & Carhart, 1966) at 45 dB HL in quiet. RESULTS: English
      proficiency ratings by Group 2 yielded sensitivity/specificity values comparable
      to those of Group 1 (Shi, 2011) in predicting word recognition. A cutoff of 8 or
      9 in minimum English proficiency rating across listening, speaking, and reading
      resulted in the best combination of prediction sensitivity/specificity. When
      relative proficiency was used, prediction of Group 1 performance significantly
      improved as compared to English proficiency. Improvement was slight for Group 2,
      mainly due to low specificity. CONCLUSION: Self-rated English proficiency
      provides clinically acceptable sensitivity/specificity values as a predictor of
      bilinguals' English word recognition. Relative proficiency has the potential to
      further improve predictive power, but the size of improvement depends on the
      characteristics of the test population.

PMID- 22992447
TI  - Speech recognition and subjective perceptions of neck-loop FM receivers with
      cochlear implants.
AB  - PURPOSE: The goal of this investigation was to determine the potential benefit of
      using electromagnetically coupled frequency modulation (FM) neck-loop receivers
      to address common communication difficulties of adults and adolescents with
      cochlear implants (CIs). METHOD: Fourteen participants with CIs used the neck
      loop FM receiver for a trial period and participated in pre- and post trial
      sessions consisting of speech-recognition-in-noise measures with and without the
      FM system and a subjective rating scale. Most participants also recorded their
      experiences during the FM-system trial period in a journal. RESULTS: The results
      suggested significantly improved speech recognition in noise with the neck-loop
      FM system before and after the trial period, with no changes in performance
      between test sessions. On average, the rating scale and journals revealed
      improvements with the FM system, relative to the CI alone, in noisy environments
      or situations at a distance from the primary talker or sound source. CONCLUSION:
      The results of the study suggest that neck-loop FM receivers significantly
      improved speech recognition in noise and everyday listening challenges of people
      using the CIs in 2 separate test sessions. Additional research is warranted for
      other types of neck-loop receivers and CI sound processors.

PMID- 22992446
TI  - Effects of advancing age and hearing loss on gaps-in-noise test performance.
AB  - PURPOSE: The present study evaluated the effects of advancing age and
      sensorineural hearing loss (SNHL) on approximate temporal gap detection
      thresholds obtained from the Gaps-in-Noise (GIN; Musiek et al., 2005) test.
      METHOD: Approximate thresholds from the GIN test were compared among 3 groups of
      participants (older adults with SNHL, older adults with essentially normal
      hearing, and young adults with normal hearing). Analyses of variance and
      regression modeling were used to determine the effect of age and audibility on
      GIN performance. Comparisons of thresholds obtained from the 4 test lists of the
      GIN were also conducted. RESULTS: Approximate gap thresholds differed
      significantly across all groups, with the poorest thresholds found in older
      adults with SNHL and with the best thresholds found in young adults with normal
      hearing. The strongest predictor of decreases in GIN performance was increased
      Audibility Index score, but a significant independent effect of age was also
      documented. Test list influenced GIN performance only in the group of young
      adults with normal hearing. CONCLUSIONS: The GIN test is a promising clinical
      measure of temporal resolution. Findings from the present study suggest that age
      and audibility influence GIN performance and may affect test analysis and
      interpretation with published normative data.

PMID- 22992448
TI  - Shear modulus measurements on isolated human lens nuclei.
AB  - The use of a spinning lens test to determine ex vivo the shear modulus of 22
      isolated human lens nuclei with ages ranging from 34 to 63 years is described. In
      this test procedure, the lens nucleus is spun about its polar axis. Images of the
      nucleus viewed from directions perpendicular to the polar axis are collected;
      these are used to quantify the deformations induced in the nucleus by the
      rotational motion. Data on these deformations are used to infer, by applying
      finite element inverse analysis, values for the shear modulus of the nucleus. The
      data on shear modulus obtained from this test program indicate that the nucleus
      stiffens very rapidly with age. These data are shown to compare well with the
      results of a related study (Wilde et al., 2012) in which the shear modulus of the
      nucleus is determined by similar spinning lens tests conducted on the entire lens
      substance.

PMID- 22992449
TI  - The effect of empowerment on the self-efficacy, quality of life and clinical and
      laboratory indicators of patients treated with hemodialysis: a randomized
      controlled trial.
AB  - BACKGROUND: Hemodialysis patients face numerous physical and psychological
      stresses that result in reduced health. The aim of this study is to determine the
      impact of an empowerment program on self-efficacy, quality of life, clinical
      indicators of blood pressure and interdialytic weight gain, and laboratory
      results in these patients. METHODS: This randomized, controlled trial was
      conducted at Boo Ali Sina Dialysis Center, Shiraz, Iran. A total of 48
      hemodialysis patients participated in this study. After acquisition of informed
      consent, eligible patients were randomly divided into two groups, control and
      experimental. Pre-test data were obtained by using a demographic data form and
      two questionnaires for self-efficacy and quality of life. Blood pressure and
      interdialytic weight gain were measured. We extracted laboratory data from
      patients' charts. A six-week empowerment intervention that included four
      individual and two group counselling sessions was performed for the experimental
      group. Six weeks after intervention, post-test data were obtained from both
      groups in the same manner as the pre-test. Data were analyzed by ANCOVA using
      SPSS v11.5. RESULTS: There were no statistically significant differences in
      demographic variables between the groups. Pre-test mean scores for self-efficacy,
      quality of life, blood pressure, interdialytic weight gain and laboratory results
      did not differ between the groups. There was a significant difference between the
      experimental and control groups in terms of pre-to post-intervention changes in
      overall self-efficacy scores, stress reduction, and decision making, in addition
      to overall quality of life and all dimensions included within quality of life
      based on this questionnaire. Additionally, the pre- to post-intervention changes
      in systolic/diastolic blood pressures, interdialytic weight gain, hemoglobin and
      hematocrit levels significantly differed between the groups. CONCLUSION: Our
      study demonstrates that a combination of individual and group empowerment
      counselling sessions improves self-efficacy, quality of life, clinical signs, and
      hemoglobin and hematocrit levels in hemodialysis patients. Empowerment of
      hemodialysis patients should be considered in hemodialysis centers to assist
      patients with the management of their health-related problems. TRIAL
      REGISTRATION: Irct ID: IRCT138901172621N4.

PMID- 22992450
TI  - Clinical relevance of serum natalizumab concentration and anti-natalizumab
      antibodies in multiple sclerosis.
AB  - BACKGROUND: Antibodies against natalizumab have been found in 4.5-14.1% of
      natalizumab-treated multiple sclerosis (MS) patients. If antibodies persist, they
      are associated with an adverse effect on treatment response. However, it has
      proved to be difficult to standardize anti-drug antibody measurements.
      OBJECTIVES: The purpose of this study was to evaluate the clinical and
      radiological impact of serum natalizumab concentrations and their relation with
      anti-natalizumab antibodies in MS patients. METHODS: In this prospective
      observational cohort study of 73 consecutive patients treated with natalizumab,
      we measured serum natalizumab levels and antibody titers before the start of
      natalizumab treatment, at weeks 12 and 24 and annually after natalizumab
      initiation. Antibodies against natalizumab were measured by radioimmunoassay and
      serum natalizumab concentrations using a newly developed enzyme linked
      immunosorbent assay (ELISA). Magnetic resonance imaging (MRI) scan and clinical
      evaluation were performed before the start of natalizumab treatment and
      subsequently every year. RESULTS: Antibodies were detected in 58% of the
      natalizumab-treated patients. All patients developed their antibodies before week
      24. The large majority of these patients reverted to neutralizing antibody (NAb)
      negative status during follow-up. The presence of antibodies was inversely
      correlated with serum natalizumab concentration (p<0.001). Only high antibody
      titers are associated with very low or undetectable serum natalizumab
      concentration. Both high antibody titers and low serum natalizumab concentrations
      are associated with relapses and gadolinium-enhancing lesions on MRI.
      CONCLUSIONS: Our data show that both low natalizumab serum concentration and high
      antibody titers are associated with a lack of efficacy of natalizumab. Measuring
      serum natalizumab, using a highly specific assay, might lead to more enhanced
      precision using natalizumab in individual patients.

PMID- 22992453
TI  - Understanding phosphatidylinositol-3-phosphate dynamics during autophagosome
      biogenesis.
AB  - Autophagosomes, the hallmark of autophagy, are double-membrane vesicles
      sequestering cytoplasmic components. They are generated at the phagophore
      assembly site (PAS), the phagophore being the precursor structure of these
      carriers. According to the current model, autophagosomes result from the
      elongation and reorganization of membranes at the PAS/phagophore driven by the
      concerted action of the autophagy-related (Atg) proteins. Once an autophagosome
      is completed, the Atg proteins that were associated with the expanding phagophore
      are released in the cytoplasm and reused for the biogenesis of new vesicles. One
      molecular event required for autophagosome formation is the generation of
      phosphatidylinositol 3-phosphate (PtdIns3P) at the PAS. Our data indicate that in
      addition to the synthesis of this lipid, the dephosphorylation of PtdIns3P is
      also crucial for autophagy progression. In the absence of Ymr1, a specific
      PtdIns3P phosphatase and the only yeast member of the myotubularin protein
      family, Atg proteins remain associated with complete autophagosomes, which are
      thus unable to fuse with the vacuole.

PMID- 22992452
TI  - Transcription termination between polo and snap, two closely spaced tandem genes
      of D. melanogaster.
AB  - Transcription termination of RNA polymerase II between closely spaced genes is an
      important, though poorly understood, mechanism. This is true, in particular, in
      the Drosophila genome, where approximately 52% of tandem genes are separated by
      less than 1 kb. We show that a set of Drosophila tandem genes has a negative
      correlation of gene expression and display several molecular marks indicative of
      promoter pausing. We find that an intergenic spacing of 168 bp is sufficient for
      efficient transcription termination between the polo-snap tandem gene pair, by a
      mechanism that is independent of Pcf11 and Xrn2. In contrast, analysis of a
      tandem gene pair containing a longer intergenic region reveals that termination
      occurs farther downstream of the poly(A) signal and is, in this case, dependent
      on Pcf11 and Xrn2. For polo-snap, displacement of poised polymerase from the snap
      promoter by depletion of the initiation factor TFIIB results in an increase of
      polo transcriptional read-through. This suggests that poised polymerase is
      necessary for transcription termination. Interestingly, we observe that polo
      forms a TFIIB dependent gene loop between its promoter and terminator regions.
      Furthermore, in a plasmid containing the polo-snap locus, deletion of the polo
      promoter causes an increase in snap expression, as does deletion of polo poly(A)
      signals. Taken together, our results indicate that polo forms a gene loop and
      polo transcription termination occurs by an Xrn2 and Pcf11 independent mechanism
      that requires TFIIB.

PMID- 22992454
TI  - Intraflagellar transport proteins cycle between the flagellum and its base.
AB  - Intraflagellar transport (IFT) is necessary for the construction of cilia and
      flagella. IFT proteins are concentrated at the base of the flagellum but little
      is known about the actual role of this pool of proteins. Here, IFT was
      investigated in Trypanosoma brucei, an attractive model for flagellum studies,
      using GFP fusions with IFT52 or the IFT dynein heavy chain DHC2.1. Tracking
      analysis by a curvelet method allowing automated separation of forward and return
      transport demonstrated a uniform speed for retrograde IFT (5 um s(-1)) but two
      distinct populations for anterograde movement that are sensitive to temperature.
      When they reach the distal tip, anterograde trains are split into three and
      converted to retrograde trains. When a fast anterograde train catches up with a
      slow one, it is almost twice as likely to fuse with it rather than to overtake
      it, implying that these trains travel on a restricted set of microtubules. Using
      photobleaching experiments, we show for the first time that IFT proteins coming
      back from the flagellum are mixed with those present at the flagellum base and
      can reiterate a full IFT cycle in the flagellum. This recycling is dependent on
      flagellum length and IFT velocities. Mathematical modelling integrating all
      parameters actually reveals the existence of two pools of IFT proteins at the
      flagellum base, but only one is actively engaged in IFT.

PMID- 22992455
TI  - Rab6 is required for the exocytosis of cortical granules and the recruitment of
      separase to the granules during the oocyte-to-embryo transition in Caenorhabditis
      elegans.
AB  - Remodeling of the embryo surface after fertilization is mediated by the
      exocytosis of cortical granules derived from the Golgi complex. This process is
      essential for oocyte-to-embryo transition in many species. However, how the
      fertilization signal reaches the cortical granules for their timely exocytosis is
      largely unknown. In Caenorhabditis elegans, the recruitment of separase, a
      downstream effector of the fertilization signal, to the cortical granules is
      essential for exocytosis because separase is required for membrane fusion.
      However, the molecule that recruits separase to the cortical granules remains
      unidentified. In this study, we found that Rab6, a Golgi-associated GTPase, is
      essential to recruit separase to the cortical granules in C. elegans embryos.
      Knockdown of the rab-6.1 gene, a Rab6 homolog in C. elegans, resulted in failure
      of the membrane fusion step of cortical granule exocytosis. Using a transgenic
      strain that expresses GFP-fused RAB-6.1, we found that RAB-6.1 temporarily co
      localized with separase on the cortical granules for a few minutes and then was
      dispersed in the cytoplasm concomitantly with membrane fusion. We found that RAB
      6.1, as well as cyclin-dependent kinase (CDK)-1 and anaphase promoting
      complex/cyclosome (APC/C), was required to recruit separase to the cortical
      granules. RAB-6.1 was not required for the chromosome segregation process, unlike
      CDK-1, APC/C and SEP-1. The results indicate that RAB-6.1 is required
      specifically for the membrane fusion step of exocytosis and for the recruitment
      of separase to the granules. Thus, RAB-6.1 is an important molecule for the
      timely exocytosis of the cortical granules during oocyte-to-embryo transition.

PMID- 22992456
TI  - Intrinsic directionality of migrating vascular smooth muscle cells is regulated
      by NAD(+) biosynthesis.
AB  - Cell migration is central to tissue repair and regeneration but must proceed with
      precise directionality to be productive. Directional migration requires external
      cues but also depends on the extent to which cells can inherently maintain their
      direction of crawling. We report that the NAD(+) biosynthetic enzyme,
      nicotinamide phosphoribosyltransferase (Nampt/PBEF/visfatin), mediates
      directionally persistent migration of vascular smooth muscle cells (SMCs). Time
      lapse microscopy of human SMCs subjected to Nampt inhibition revealed chaotic
      motility whereas SMCs transduced with the Nampt gene displayed highly linear
      migration paths. Ordered motility conferred by Nampt was associated with
      downsizing of the lamellipodium, reduced lamellipodium wandering around the cell
      perimeter, and increased lamellipodial protrusion rates. These protrusive and
      polarity-stabilizing effects also enabled spreading SMCs to undergo bipolar
      elongation to an extent not typically observed in vitro. Nampt was found to
      localize to lamellipodia and fluorescence recovery of Nampt-eGFP after
      photobleaching revealed microtubule-dependent transport of Nampt to the leading
      edge. In addition, Nampt was found to associate with, and activate, Cdc42, and
      Nampt-driven directional persistence and lamellipodium anchoring required Cdc42.
      We conclude that high-fidelity SMC motility is coordinated by a Nampt-Cdc42 axis
      that yields protrusive but small and anchored lamellipodia. This novel, NAD(+)
      synthesis-dependent control over motility may be crucial for efficient repair and
      regeneration of the vasculature, and possibly other tissues.

PMID- 22992457
TI  - Microtubule guidance tested through controlled cell geometry.
AB  - In moving cells dynamic microtubules (MTs) target and disassemble substrate
      adhesion sites (focal adhesions; FAs) in a process that enables the cell to
      detach from the substrate and propel itself forward. The short-range interactions
      between FAs and MT plus ends have been observed in several experimental systems,
      but the spatial overlap of these structures within the cell has precluded
      analysis of the putative long-range mechanisms by which MTs growing through the
      cell body reach FAs in the periphery of the cell. In the work described here cell
      geometry was controlled to remove the spatial overlap of cellular structures thus
      allowing for unambiguous observation of MT guidance. Specifically,
      micropatterning of living cells was combined with high-resolution in-cell imaging
      and gene product depletion by means of RNA interference to study the long-range
      MT guidance in quantitative detail. Cells were confined on adhesive triangular
      microislands that determined cell shape and ensured that FAs localized
      exclusively at the vertices of the triangular cells. It is shown that initial MT
      nucleation at the centrosome is random in direction, while the alignment of MT
      trajectories with the targets (i.e. FAs at vertices) increases with an increasing
      distance from the centrosome, indicating that MT growth is a non-random, guided
      process. The guided MT growth is dependent on the presence of FAs at the
      vertices. The depletion of either myosin IIA or myosin IIB results in depletion
      of F-actin bundles and spatially unguided MT growth. Taken together our findings
      provide quantitative evidence of a role for long-range MT guidance in MT
      targeting of FAs.

PMID- 22992458
TI  - The Drosophila Arf1 homologue Arf79F is essential for lamellipodium formation.
AB  - The WAVE regulatory complex (WRC) drives the polymerisation of actin filaments
      located beneath the plasma membrane to generate lamellipodia that are pivotal to
      cell architecture and movement. By reconstituting WRC-dependent actin assembly at
      the membrane, we recently discovered that several classes of Arf family GTPases
      directly recruit and activate WRC in cell extracts, and that Arf cooperates with
      Rac1 to trigger actin polymerisation. Here, we demonstrate that the Class 1 Arf1
      homologue Arf79F colocalises with the WRC at dynamic lamellipodia. We report that
      Arf79F is required for lamellipodium formation in Drosophila S2R+ cells, which
      only express one Arf isoform for each class. Impeding Arf function either by
      dominant-negative Arf expression or by Arf double-stranded RNA interference
      (dsRNAi)-mediated knockdown uncovered that Arf-dependent lamellipodium formation
      was specific to Arf79F, establishing that Class 1 Arfs, but not Class 2 or Class
      3 Arfs, are crucial for lamellipodia. Lamellipodium formation in Arf79F-silenced
      cells was restored by expressing mammalian Arf1, but not by constitutively active
      Rac1, showing that Arf79F does not act via Rac1. Abolition of lamellipodium
      formation in Arf79F-silenced cells was not due to Golgi disruption. Blocking
      Arf79F activation with guanine nucleotide exchange factor inhibitors impaired WRC
      localisation to the plasma membrane and concomitant generation of lamellipodia.
      Our data indicate that the Class I Arf GTPase is a central component in WRC
      driven lamellipodium formation.

PMID- 22992459
TI  - Dock mediates Scar- and WASp-dependent actin polymerization through interaction
      with cell adhesion molecules in founder cells and fusion-competent myoblasts.
AB  - The formation of the larval body wall musculature of Drosophila depends on the
      asymmetric fusion of two myoblast types, founder cells (FCs) and fusion-competent
      myoblasts (FCMs). Recent studies have established an essential function of Arp2/3
      based actin polymerization during myoblast fusion, formation of a dense actin
      focus at the site of fusion in FCMs, and a thin sheath of actin in FCs and/or
      growing muscles. The formation of these actin structures depends on recognition
      and adhesion of myoblasts that is mediated by cell surface receptors of the
      immunoglobulin superfamily. However, the connection of the cell surface receptors
      with Arp2/3-based actin polymerization is poorly understood. To date only the SH2
      SH3 adaptor protein Crk has been suggested to link cell adhesion with Arp2/3
      based actin polymerization in FCMs. Here, we propose that the SH2-SH3 adaptor
      protein Dock, like Crk, links cell adhesion with actin polymerization. We show
      that Dock is expressed in FCs and FCMs and colocalizes with the cell adhesion
      proteins Sns and Duf at cell-cell contact points. Biochemical data in this study
      indicate that different domains of Dock are involved in binding the cell adhesion
      molecules Duf, Rst, Sns and Hbs. We emphasize the importance of these
      interactions by quantifying the enhanced myoblast fusion defects in duf dock, sns
      dock and hbs dock double mutants. Additionally, we show that Dock interacts
      biochemically and genetically with Drosophila Scar, Vrp1 and WASp. Based on these
      data, we propose that Dock links cell adhesion in FCs and FCMs with either Scar-
      or Vrp1-WASp-dependent Arp2/3 activation.

PMID- 22992460
TI  - Activity of PLCepsilon contributes to chemotaxis of fibroblasts towards PDGF.
AB  - Cell chemotaxis, such as migration of fibroblasts towards growth factors during
      development and wound healing, requires precise spatial coordination of
      signalling events. Phosphoinositides and signalling enzymes involved in their
      generation and hydrolysis have been implicated in regulation of chemotaxis;
      however, the role and importance of specific components remain poorly understood.
      Here, we demonstrate that phospholipase C epsilon (PLCepsilon) contributes to
      fibroblast chemotaxis towards platelet-derived growth factor (PDGF-BB). Using
      PLCe1 null fibroblasts we show that cells deficient in PLCepsilon have greatly
      reduced directionality towards PDGF-BB without detrimental effect on their basal
      ability to migrate. Furthermore, we show that in intact fibroblasts, signalling
      events, such as activation of Rac, are spatially compromised by the absence of
      PLCepsilon that affects the ability of cells to enlarge their protrusions in the
      direction of the chemoattractant. By further application of live cell imaging and
      the use of FRET-based biosensors, we show that generation of Ins(1,4,5)P(3) and
      recruitment of PLCepsilon are most pronounced in protrusions responding to the
      PDGF-BB gradient. Furthermore, the phospholipase C activity of PLCepsilon is
      critical for its role in chemotaxis, consistent with the importance of
      Ins(1,4,5)P(3) generation and sustained calcium responses in this process. As
      PLCepsilon has extensive signalling connectivity, using transgenic fibroblasts we
      ruled out its activation by direct binding to Ras or Rap GTPases, and suggest
      instead new unexpected links for PLCepsilon in the context of chemotaxis.

PMID- 22992461
TI  - The role of microtubules in neutrophil polarity and migration in live zebrafish.
AB  - Microtubules control cell motility by positively regulating polarization in many
      cell types. However, how microtubules regulate leukocyte migration is not well
      understood, particularly in living organisms. Here we exploited the zebrafish
      system to study the role of microtubules in neutrophil migration in vivo. The
      localization of microtubules was visualized in motile neutrophils using various
      bioprobes, revealing that, in contrast to what has been seen in studies in vitro,
      the microtubule organizing center is positioned in front of the nucleus (relative
      to the direction of migration) in motile neutrophils. Microtubule disassembly
      impaired attraction of neutrophils to wounds but enhanced the polarity of F-actin
      dynamics as measured by the distribution of stable and dynamic F-actin.
      Microtubule depolymerization inhibited polarized phosphoinositol 3-kinase
      (PI(3)K) activation at the leading edge and induced rapid PI(3)K independent
      motility. Finally, we show that microtubules exert their effects on neutrophil
      polarity and motility at least in part by the negative regulation of both Rho and
      Rac activity. These results provide new insight into the role of microtubules in
      neutrophil migration in a living vertebrate and show that the motility of these
      professional migratory cells are subject to distinctly different rules from those
      established for other cell types.

PMID- 22992462
TI  - The Nramp (Slc11) proteins regulate development, resistance to pathogenic
      bacteria and iron homeostasis in Dictyostelium discoideum.
AB  - The Dictyostelium discoideum genome harbors two genes encoding members of the
      Nramp superfamily, which is conserved from bacteria (MntH proteins) to humans
      (Slc11 proteins). Nramps are proton-driven metal ion transporters with a
      preference for iron and manganese. Acquisition of these metal cations is vital
      for all cells, as they act as redox cofactors and regulate key cellular
      processes, such as DNA synthesis, electron transport, energy metabolism and
      oxidative stress. Dictyostelium Nramp1 (Slc11a1), like its mammalian ortholog,
      mediates resistance to infection by invasive bacteria. We have extended the
      analysis to the nramp2 gene, by generating single and double nramp1/nramp2
      knockout mutants and cells expressing GFP fusion proteins. In contrast to Nramp1,
      which is recruited to phagosomes and macropinosomes, the Nramp2 protein is
      localized exclusively in the membrane of the contractile vacuole, a vesicular
      tubular network regulating cellular osmolarity. Both proteins colocalize with the
      V-H(+)-ATPase, which can provide the electrogenic force for vectorial transport.
      Like nramp1, nramp2 gene disruption affects resistance to Legionella pneumophila.
      Disrupting both genes additionally leads to defects in development, with strong
      delay in cell aggregation, formation of large streams and multi-tipped
      aggregates. Single and double mutants display differential sensitivity to cell
      growth under conditions of iron overload or depletion. The data favor the
      hypothesis that Nramp1 and Nramp2, under control of the V-H(+)-ATPase,
      synergistically regulate iron homeostasis, with the contractile vacuole possibly
      acting as a store for metal cations.

PMID- 22992463
TI  - FGF receptors 1 and 2 are key regulators of keratinocyte migration in vitro and
      in wounded skin.
AB  - Efficient wound repair is essential for the maintenance of the integrity of the
      skin. The repair process is controlled by a variety of growth factors and
      cytokines, and their abnormal expression or activity can cause healing disorders.
      Here, we show that wound repair is severely delayed in mice lacking fibroblast
      growth factor receptors (FGFR) 1 and 2 in keratinocytes. As the underlying
      mechanism, we identified impaired wound contraction and a delay in re
      epithelialization that resulted from impaired keratinocyte migration at the wound
      edge. Scratch wounding and transwell assays demonstrated that FGFR1/2-deficient
      keratinocytes had a reduced migration velocity and impaired directional
      persistence owing to inefficient formation and turnover of focal adhesions.
      Underlying this defect, we identified a significant reduction in the expression
      of major focal adhesion components in the absence of FGFR signaling, resulting in
      a general migratory deficiency. These results identify FGFs as key regulators of
      keratinocyte migration in wounded skin.

PMID- 22992464
TI  - Dynamics of clathrin-mediated endocytosis and its requirement for organelle
      biogenesis in Dictyostelium.
AB  - The protein clathrin mediates one of the major pathways of endocytosis from the
      extracellular milieu and plasma membrane. In single-cell eukaryotes, such as
      Saccharomyces cerevisiae, the gene encoding clathrin is not an essential gene,
      raising the question of whether clathrin conveys specific advantages for
      multicellularity. Furthermore, in contrast to mammalian cells, endocytosis in S.
      cerevisiae is not dependent on either clathrin or adaptor protein 2 (AP2), an
      endocytic adaptor molecule. In this study, we investigated the requirement for
      components of clathrin-mediated endocytosis (CME) in another unicellular
      organism, the amoeba Dictyostelium. We identified a heterotetrameric AP2 complex
      in Dictyostelium that is similar to that which is found in higher eukaryotes. By
      simultaneously imaging fluorescently tagged clathrin and AP2, we found that,
      similar to higher eukaryotes, these proteins colocalized to membrane puncta that
      move into the cell together. In addition, the contractile vacuole marker protein,
      dajumin-green fluorescent protein (GFP), is trafficked via the cell membrane and
      internalized by CME in a clathrin-dependent, AP2-independent mechanism. This
      pathway is distinct from other endocytic mechanisms in Dictyostelium. Our finding
      that CME is required for the internalization of contractile vacuole proteins from
      the cell membrane explains the contractile vacuole biogenesis defect in
      Dictyostelium cells lacking clathrin. Our results also suggest that the machinery
      for CME and its role in organelle maintenance appeared early during eukaryotic
      evolution. We hypothesize that dependence of endocytosis on specific components
      of the CME pathway evolved later, as demonstrated by internalization independent
      of AP2 function.

PMID- 22992465
TI  - Zasp regulates integrin activation.
AB  - Integrins are heterodimeric adhesion receptors that link the extracellular matrix
      (ECM) to the cytoskeleton. Binding of the scaffold protein, talin, to the
      cytoplasmic tail of beta-integrin causes a conformational change of the
      extracellular domains of the integrin heterodimer, thus allowing high-affinity
      binding of ECM ligands. This essential process is called integrin activation.
      Here we report that the Z-band alternatively spliced PDZ-motif-containing protein
      (Zasp) cooperates with talin to activate alpha5beta1 integrins in mammalian
      tissue culture and alphaPS2betaPS integrins in Drosophila. Zasp is a PDZ-LIM
      domain-containing protein mutated in human cardiomyopathies previously thought to
      function primarily in assembly and maintenance of the muscle contractile
      machinery. Notably, Zasp is the first protein shown to co-activate alpha5beta1
      integrins with talin and appears to do so in a manner distinct from known
      alphaIIbbeta3 integrin co-activators.

PMID- 22992466
TI  - Voltage-gated sodium channels and metastatic disease.
AB  - Voltage-gated Na (+)  channels (VGSCs) are macromolecular protein complexes
      containing a pore-forming alpha subunit and smaller non-pore-forming beta
      subunits. VGSCs are expressed in metastatic cells from a number of cancers. In
      these cells, Na (+)  current carried by alpha subunits enhances migration,
      invasion and metastasis in vivo. In contrast, the beta subunits mediate cellular
      adhesion and process extension. The prevailing hypothesis is that VGSCs are
      upregulated in cancer, in general favoring an invasive/metastatic phenotype,
      although the mechanisms are still not fully clear. Expression of the Nav 1.5
      alpha subunit associates with poor prognosis in clinical breast cancer specimens,
      suggesting that VGSCs may have utility as prognostic markers for cancer
      progression. Furthermore, repurposing existing VGSC-blocking therapeutic drugs
      may provide a new strategy to improve outcomes in patients suffering from
      metastatic disease, which is the major cause of cancer-related deaths, and for
      which there is currently no cure.

PMID- 22992467
TI  - In vivo multiphoton imaging of mitochondrial structure and function during acute
      kidney injury.
AB  - Mitochondrial dysfunction has been implicated in the pathogenesis of acute kidney
      injury due to ischemia and toxic drugs. Methods for imaging mitochondrial
      function in cells using confocal microscopy are well established; more recently,
      it was shown that these techniques can be utilized in ex vivo kidney tissue using
      multiphoton microscopy. We extended this approach in vivo and found that kidney
      mitochondrial structure and function can be imaged in anesthetized rodents using
      multiphoton excitation of endogenous and exogenous fluorophores. Mitochondrial
      nicotinamide adenine dinucleotide increased markedly in rat kidneys in response
      to ischemia. Following intravenous injection, the mitochondrial membrane
      potential-dependent dye TMRM was taken up by proximal tubules; in response to
      ischemia, the membrane potential dissipated rapidly and mitochondria became
      shortened and fragmented in proximal tubules. In contrast, the mitochondrial
      membrane potential and structure were better maintained in distal tubules.
      Changes in mitochondrial structure, nicotinamide adenine dinucleotide, and
      membrane potential were found in the proximal, but not distal, tubules after
      gentamicin exposure. These changes were sporadic, highly variable among animals,
      and were preceded by changes in non-mitochondrial structures. Thus, real-time
      changes in mitochondrial structure and function can be imaged in rodent kidneys
      in vivo using multiphoton excitation of endogenous and exogenous fluorophores in
      response to ischemia-reperfusion injury or drug toxicity.

PMID- 22992468
TI  - Temporal trends in the incidence of kidney stone disease.
AB  - Recent reports show an increased occurrence of kidney stone disease worldwide. To
      further evaluate and quantify this observation, we examined recent trends in the
      incidence of kidney stone disease in the adult population of Iceland over a 24
      year period. Computerized databases of all major hospitals and medical imaging
      centers in Iceland were searched for International Classification of Diseases,
      radiologic and surgical procedure codes indicative of kidney stones in patients
      aged 18 years and older. The time trends in stone frequency of 5945 incident
      patients (63% men) were assessed by Poisson regression analysis. The majority of
      patients (90.5%) had symptomatic stone disease. The total incidence of kidney
      stones rose significantly from 108 per 100,000 in the first 5-year interval of
      the study to 138 per 100,000 in the last interval. The annual incidence of
      symptomatic stones did not increase significantly in either men or women. There
      was, however, a significant increase in the annual incidence of asymptomatic
      stones over time, from 7 to 24 per 100,000 for men and from 7 to 21 per 100,000
      for women. The increase in the incidence of asymptomatic stones was only
      significant for women above 50 years of age and for men older than 40 years.
      Thus, we found a significant increase in the incidence of kidney stone disease
      resulting from increased detection of asymptomatic stones. This was largely due
      to a more frequent use of high-resolution imaging studies in older patients.

PMID- 22992469
TI  - Chronic kidney disease alters intestinal microbial flora.
AB  - The population of microbes (microbiome) in the intestine is a symbiotic ecosystem
      conferring trophic and protective functions. Since the biochemical environment
      shapes the structure and function of the microbiome, we tested whether uremia
      and/or dietary and pharmacologic interventions in chronic kidney disease alters
      the microbiome. To identify different microbial populations, microbial DNA was
      isolated from the stools of 24 patients with end-stage renal disease (ESRD) and
      12 healthy persons, and analyzed by phylogenetic microarray. There were marked
      differences in the abundance of 190 bacterial operational taxonomic units (OTUs)
      between the ESRD and control groups. OTUs from Brachybacterium, Catenibacterium,
      Enterobacteriaceae, Halomonadaceae, Moraxellaceae, Nesterenkonia, Polyangiaceae,
      Pseudomonadaceae, and Thiothrix families were markedly increased in patients with
      ESRD. To isolate the effect of uremia from inter-individual variations, comorbid
      conditions, and dietary and medicinal interventions, rats were studied 8 weeks
      post 5/6 nephrectomy or sham operation. This showed a significant difference in
      the abundance of 175 bacterial OTUs between the uremic and control animals, most
      notably as decreases in the Lactobacillaceae and Prevotellaceae families. Thus,
      uremia profoundly alters the composition of the gut microbiome. The biological
      impact of this phenomenon is unknown and awaits further investigation.

PMID- 22992470
TI  - A high throughput and sensitive method correlates neuronal disorder genotypes to
      Drosophila larvae crawling phenotypes.
AB  - Drosophila melanogaster is widely used as a model system for development and
      disease. Due to the homology between Drosophila and human genes, as well as the
      tractable genetics of the fly, its use as a model for neurologic disorders, in
      particular, has been rising. Locomotive impairment is a commonly used diagnostic
      for screening and characterization of these models, yet a fast, sensitive and
      model-free method to compare behavior is lacking. Here, we present a high
      throughput method to quantify the crawling behavior of larvae. We use the mean
      squared displacement as well as the direction autocorrelation of the crawling
      larvae as descriptors of their motion. By tracking larvae from wild-type strains
      and models of the Fragile X mental retardation as well as Alzheimer disease, we
      show these mutants exhibit impaired crawling. We further show that the magnitude
      of impairment correlates with the severity of the mutation, demonstrating the
      sensitivity and the dynamic range of the method. Finally, we study larvae with
      altered expression of the shaggy gene, a homolog of Glycogen Synthase Kinase-3
      (GSK-3), which has been implicated in Alzheimer disease. Surprisingly, we find
      that both increased and decreased expression of dGSK-3 lead to similar larval
      crawling impairment. These findings have implications for the use of GSK-3
      inhibitors recently proposed for Alzheimer treatment.

PMID- 22992471
TI  - Interleukin 12 receptor deficiency in a child with recurrent bronchopneumonia and
      very high IgE levels.
AB  - Interleukin-12 (IL-12) is involved in cellular immune responses against
      intracellular pathogens by promoting the generation of T naive in T helper 1
      (Th1) cells and by increasing interferon-gamma (IFN-gamma) production from T and
      natural killer (NK) cells. A defective induction of a Th1 response may lead to a
      higher risk of infections, and, in particular, infections due to typical and
      atypical Mycobacteria. We report on the case of a girl with suffering from
      recurrent bronchopneumonia associated with very high serum IgE levels, who
      exhibited a profound impairment of the Th1 generation associated with a novel
      mutation in the exon 5 of the IL-12R beta1 gene (R156H). Our data suggest that in
      children with severe and recurrent infections, even in the absence of a
      mycobacterial infection, functional and/or genetic alterations of the molecular
      mechanisms governing Th1/Th2 homeostasis might be responsible for an atypical
      immunodeficiency and, therefore, should be investigated in these patients.

PMID- 22992472
TI  - Effect of homotypic and heterotypic interaction in 3D on the E-selectin mediated
      adhesive properties of breast cancer cell lines.
AB  - Hematogenous metastasis involves a glycoprotein mediated adhesion cascade of
      tumor cells with E-selectin on the endothelial layer of the blood vessels. Cell
      cell interactions play a major role in cancer metastasis and invasiveness.
      Intercellular communication between two cancer cells or between a cancer cell
      with a stromal cell in the microenvironment such as fibroblasts or inflammatory
      cells play an important role in metastatic invasion. Culturing tumor cells as 3D
      spheroids can recapitulate these physiologically relevant cell-cell interactions.
      The heterogeneity in primary tumors is attributed to cell subpopulations with
      varying degree of invasiveness. Co-culturing cancer cells with different
      phenotypes as 3D spheroids can mimic this heterogeneity. Here we report the
      effect of homotypic and heterotypic interactions in breast cancer cells cultured
      as 3D spheroids on polydimethylsiloxane (PDMS) on the adhesion phenotype to E
      selectin. We show that breast cancer cell lines (BT20 and MCF7) propagating as 3D
      spheroids on PDMS exhibit a stronger interaction with human recombinant E
      selectin when compared to their respective monolayer grown counterparts on tissue
      culture plate (TCP). Matrigel invasion assay also indicated that BT20 and MCF7
      spheroids were more invasive than BT20 and MCF7 cells grown as monolayers. To
      mimic tumor heterogeneity in vitro, a co-culture model included tumorigenic cell
      lines BT20, MCF7 and a non-tumorigenic mammary epithelial cell line MCF10A. These
      cell lines were cultured together in equal seeding ratio on PDMS to generate co
      culture spheroids. The heterotypic interactions in the co-culture model resulted
      in enhancement of the adhesion of the most invasive BT20 cell line to E-selectin.
      BT20 cells in co-culture bound to the greatest degree to soluble E-selectin
      compared to MCF7 and MCF10A cells in co-culture. Co-invasion assay with co
      culture spheroids indicated that BT20 cells in co-culture were more invasive than
      MCF7 and MCF10A cells. The results presented here indicate that homotypic and
      heterotypic interaction of cancer cells favor adhesion to E-selectin thus
      representing a complexity beyond planar cell culture. Also, when cells of
      different phenotypes are mixed, the heterogeneity enhances the adhesive phenotype
      and invasiveness of the most invasive cell population. The results challenge the
      classic use of planar cell culture for evaluating the adhesion of cancer cells to
      E-selectin and establish our co-culture technique as a model that can help
      investigative studies in metastasis and invasiveness of breast and other types of
      cancers.

PMID- 22992473
TI  - Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.
AB  - Malignant melanoma involving the respiratory tract is nearly always metastatic in
      origin, and primary tumors are very rare. To our knowledge, about 30 cases have
      been reported in the English literature, one of which involved multiple brain
      metastases. Here, we report two cases of primary pulmonary malignant melanoma.
      The first case, which occurred in a 52-year-old Chinese female patient who died 4
      months after the initial diagnosis, involved rapid intrapulmonary and
      intracranial metastases. The second patient, a 65-year-old female, underwent
      surgical excision, and clinical examination, histopathological characteristics,
      and immunohistochemical features supported the diagnosis of pulmonary malignant
      melanoma. No evidence for recurrence and/or metastasis has been found more than
      one year after the initial surgery. To establish the diagnosis of primary
      pulmonary malignant melanoma, any extrapulmonary origin must be excluded by
      detailed examination. Moreover, the tumor should be removed surgically whether it
      occurs as a single lesion or multiple lesions. VIRTUAL SLIDE: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

PMID- 22992474
TI  - A near-infrared fluorescent turn-on probe for fluorescence imaging of hydrogen
      sulfide in living cells based on thiolysis of dinitrophenyl ether.
AB  - We have constructed a novel NIR fluorescent turn-on hydrogen sulfide probe
      suitable for fluorescent imaging in living cells based on thiolysis of
      dinitrophenyl ether.

PMID- 22992475
TI  - [Response rates for surveys is a challenge].

PMID- 22992476
TI  - [Undocumented migrants in health care is a serious challenge].

PMID- 22992477
TI  - [The Danish Health Act and health-care services to undocumented migrants].
AB  - Health-care workers may experience uncertainty regarding legal matters when
      attending to medical needs of undocumented migrants. This paper applies a
      pragmatic focus when addressing the legal aspects involved in providing health
      care services to undocumented migrants with examples from the Danish Health Act
      and international conventions. The delivery of medical care to vulnerable groups
      such as pregnant women and children is described.

PMID- 22992478
TI  - [Surgical treatment of anal fistulas in Crohn's disease].
AB  - The treatment of transsphincteric anal fistulas in Crohn's disease is a balance
      between the elimination of the sepsis and the functional outcome. Loose setons
      can be used as a preoperative drainage or chronic treatment. Fibrin glue and the
      anal fistula plug are methods with excellent functional outcomes, but the success
      rate varies. The endorectal advancement flap is considered to be the gold
      standard. Ligation of the intersphincteric fistula tract is promising.
      Proctectomy or proctocolectomy in combination with transposition flaps may be
      necessary. A success rate of 66-70% has been reported.

PMID- 22992479
TI  - [Preoperative assessment of surgical patients with hypertension arterialis].
AB  - Almost one out of four patients referred for non cardiac surgery presents
      preoperatively with hypertensio arterialis (HA). The risk of perioperative
      cardiovascular complication increases with the grade of HA and the coexistence of
      end organ damage. This paper is a review of the current knowledge of HA and
      anaesthesia. It is recommended that patients with grade I and II HA proceed for
      surgery. But the evidence for patients with grade III HA is less clear. Patients
      without end organ damage can proceed for surgery, while patients with end organ
      damage should be stabilized before surgery.

PMID- 22992480
TI  - [Clinical guidelines for antithrombotic therapy of patients with atrial
      fibrillation can be implemented in general practice by means of data capture].
AB  - Suboptimal treatment with oral anticoagulation therapy of atrial fibrillation is
      well-documented. The use of clinical guidelines and databases in general practice
      can improve adherence to the guidelines stipulated by the Danish Society of
      Cardiology. However, guidelines should be updated continuously, and in
      approximately 20% of our patients the application of oral anticoagulation therapy
      turned out to be problematic, even though they had a high thromboembolic risk
      score.

PMID- 22992481
TI  - [Boerhaave's syndrome can be a rare cause of tension pneumothorax].
AB  - We report a case of tension pneumothorax as an initial symptom caused by
      spontaneous rupture of the distal oesophagus (Boerhaave's syndrome). Prompt
      recognition of this potentially lethal syndrome is essential. The best way to
      diagnose the syndrome is by performing an oesophagram.

PMID- 22992482
TI  - [Superficial siderosis of the central nervous system treated with prednisolone].
AB  - Superficial siderosis (SS) of the central nervous system is a rare disorder in
      which the most common clinical manifestations are gait ataxia, sensorineural
      deafness and affection of the corticospinal tracts. Knowledge of this disorder is
      important since early diagnosis and treatment is crucial for the prognosis.
      Furthermore, new treatment strategies are emerging. The effect of corticosteroids
      on SS without an identifiable bleeding source has been debated. We present a case
      with a good clinical effect of steroids.

PMID- 22992483
TI  - Molecular breeding of Osfer 2 gene to increase iron nutrition in rice grain.
AB  - Rice being a staple food, contains little iron in the edible grain. To increase
      the iron nutrition in rice grains, our present study highlights the first time
      development of high iron rice grain by exploring the endosperm specific
      overexpression of endogenous ferritin gene. The gene has been cloned from rice
      and overexpressed under the control of endosperm specific GlutelinA2 (OsGluA 2)
      promoter. After genetic transformation of aromatic indica rice cultivar, Pusa
      sugandhi II, the milled seeds of resulting T 3 transgenics exhibited 7.8-fold of
      ferritin overexpression, which contributed to 2.09- and 1.37-fold of iron and
      zinc accumulation respectively. T 3 seeds demonstrated endosperm specific
      localization of iron that confirms the tissue specific activity of GluA2
      promoter. Transgenic and non-transgenic plants showed no difference in their
      agronomic traits. Our study suggested that overexpression of rice endogenous
      ferritin gene is a step ahead toward cisgenic approach and can act as an
      effective tool for iron biofortification.

PMID- 22992484
TI  - Controlling cost escalation of healthcare: making universal health coverage
      sustainable in China.
AB  - An increasingly number of low- and middle-income countries have developed and
      implemented a national policy towards universal coverage of healthcare for their
      citizens over the past decade. Among them is China which has expanded its
      population coverage by health insurance from around 29.7% in 2003 to over 90% at
      the end of 2010. While both central and local governments in China have
      significantly increased financial inputs into the two newly established health
      insurance schemes: new cooperative medical scheme (NCMS) for the rural
      population, and urban resident basic health insurance (URBMI), the cost of
      healthcare in China has also been rising rapidly at the annual rate of 17.0%%
      over the period of the past two decades years. The total health expenditure
      increased from 74.7 billion Chinese yuan in 1990 to 1998 billion Chinese yuan in
      2010, while average health expenditure per capital reached the level of 1490.1
      Chinese yuan per person in 2010, rising from 65.4 Chinese yuan per person in
      1990. The repaid increased population coverage by government supported health
      insurance schemes has stimulated a rising use of healthcare, and thus given rise
      to more pressure on cost control in China.There are many effective measures of
      supply-side and demand-side cost control in healthcare available. Over the past
      three decades China had introduced many measures to control demand for health
      care, via a series of co-payment mechanisms. The paper introduces and discusses
      new initiatives and measures employed to control cost escalation of healthcare in
      China, including alternative provider payment methods, reforming drug procurement
      systems, and strengthening the application of standard clinical paths in treating
      patients at hospitals, and analyses the impacts of these initiatives and
      measures. The paper finally proposes ways forward to make universal health
      coverage in China more sustainable.

PMID- 22992485
TI  - Molecular and functional determinants of local anesthetic inhibition of NaChBac.
AB  - In our recent publication, we describe the local anesthetic (LA) inhibition of
      the prokaryotic voltage gated sodium channel NaChBac. Despite the numerous
      functional and putative structural differences with the mammalian sodium
      channels, the data show that LA compounds effectively and reversibly inhibit
      NaChBac channels in a concentration range similar to resting blockade on
      eukaryotic Navs. In addition to current reduction, LA application accelerated
      channel inactivation kinetics of NaChBac which could be accounted for in a simple
      state-model whereby local anesthetics increase the probability of entering the
      inactivated state. We have further explored what state (or states) local
      anesthetic blockade of NaChBac could pertain to eukaryotic sodium channels, and
      what molecular similarities exist between these disparate channel families. Here
      we show that the rate of recovery from inactivation remains unaffected in the
      presence of local anesthetics. Further, we show that two sites that support use
      dependent inhibition in eukaryotic channels, do not affect block to the same
      extent when mutated in NaChBac channels. The data indicate that the molecular
      determinants and the inherent mechanisms for LA block are likely to be divergent
      between bacterial and eukaryotic Navs, but future experiments will help define
      possible similarities.

PMID- 22992487
TI  - 2 new drugs for weight loss.

PMID- 22992486
TI  - Identification of different trypanosome species in the mid-guts of tsetse flies
      of the Malanga (Kimpese) sleeping sickness focus of the Democratic Republic of
      Congo.
AB  - BACKGROUND: The Malanga sleeping sickness focus of the Democratic Republic of
      Congo has shown an epidemic evolution of disease during the last century.
      However, following case detection and treatment, the prevalence of the disease
      decreased considerably. No active survey has been undertaken in this focus for a
      couple of years. To understand the current epidemiological status of sleeping
      sickness as well as the animal African trypanosomiasis in the Malanga focus, we
      undertook the identification of tsetse blood meals as well as different
      trypanosome species in flies trapped in this focus. METHODS: Pyramidal traps were
      use to trap tsetse flies. All flies caught were identified and live flies were
      dissected and their mid-guts collected. Fly mid-gut was used for the molecular
      identification of the blood meal source, as well as for the presence of different
      trypanosome species. RESULTS: About 949 Glossina palpalis palpalis were trapped;
      296 (31.2%) of which were dissected, 60 (20.3%) blood meals collected and 57
      (19.3%) trypanosome infections identified. The infection rates were 13.4%, 5.1%,
      3.5% and 0.4% for Trypanosoma congolense savannah type, Trypanosoma brucei s.l.,
      Trypanosoma congolense forest type and Trypanosoma vivax, respectively. Three
      mixed infections including Trypanosoma brucei s.l. and Trypanosoma congolense
      savannah type, and one mixed infection of Trypanosoma vivax and Trypanosoma
      congolense savannah type were identified. Eleven Trypanosoma brucei gambiense
      infections were identified; indicating an active circulation of this trypanosome
      subspecies. Of all the identified blood meals, about 58.3% were identified as
      being taken on pigs, while 33.3% and 8.3% were from man and other mammals,
      respectively. CONCLUSION: The presence of Trypanosoma brucei in tsetse mid-guts
      associated with human blood meals is indicative of an active transmission of this
      parasite between tsetse and man. The considerable number of pig blood meals
      combined with the circulation of Trypanosoma brucei gambiense in this focus
      suggests a transmission cycle involving humans and domestic animals and could
      hamper eradication strategies. The various species of trypanosomes identified in
      the Malanga sleeping sickness focus indicates the coexistence of animal and human
      African Trypanosomiasis. The development of new strategies integrating control
      measures for human and animal trypanosomiasis may enable the reduction of the
      control costs in this locality.

PMID- 22992488
TI  - Citalopram (Celexa) and QT interval prolongation.

PMID- 22992489
TI  - Data-driven analysis of analogous brain networks in monkeys and humans during
      natural vision.
AB  - Inferences about functional correspondences between functional networks of human
      and non-human primates largely rely on proximity and anatomical expansion models.
      However, it has been demonstrated that topologically correspondent areas in two
      species can have different functional properties, suggesting that anatomy-based
      approaches should be complemented with alternative methods to perform functional
      comparisons. We have recently shown that comparative analyses based on temporal
      correlations of sensory-driven fMRI responses can reveal functional correspondent
      areas in monkeys and humans without relying on spatial assumptions. Inter-species
      activity correlation (ISAC) analyses require the definition of seed areas in one
      species to reveal functional correspondences across the cortex of the same and
      other species. Here we propose an extension of the ISAC method that does not rely
      on any seed definition, hence a method void of any spatial assumption.
      Specifically, we apply independent component analysis (ICA) separately to monkey
      and human data to define species-specific networks of areas with coherent
      stimulus-related activity. Then, we use a hierarchical cluster analysis to
      identify ICA-based ISAC clusters of monkey and human networks with similar
      timecourses. We implemented this approach on fMRI data collected in monkeys and
      humans during movie watching, a condition that evokes widespread sensory-driven
      activity throughout large portions of the cortex. Using ICA-based ISAC, we
      detected seven monkey-human clusters. The timecourses of several clusters showed
      significant correspondences either with the motion energy in the movie or with
      eye-movement parameters. Five of the clusters spanned putative homologous
      functional networks in either primary or extrastriate visual regions, whereas two
      clusters included higher-level visual areas at topological locations that are not
      predicted by cortical surface expansion models. Overall, our ICA-based ISAC
      analysis complemented the findings of our previous seed-based investigations, and
      suggested that functional processes can be executed by brain networks in
      different species that are functionally but not necessarily anatomically
      correspondent. Overall, our method provides a novel approach to reveal evolution
      driven functional changes in the primate brain with no spatial assumptions.

PMID- 22992490
TI  - Brain activation patterns during visual episodic memory processing among first
      degree relatives of schizophrenia subjects.
AB  - Episodic memory deficits are proposed as a potential intermediate phenotype of
      schizophrenia. We examined deficits in visual episodic memory and associated
      brain activation differences among early course schizophrenia (n=22), first
      degree relatives (n=16) and healthy controls without personal or family history
      of psychotic disorders (n=28). Study participants underwent functional magnetic
      resonance imaging on a 3T scanner while performing visual episodic memory
      encoding and retrieval task. We examined in-scanner behavioral performance
      evaluating response time and accuracy of performance. Whole-brain BOLD response
      differences were analyzed using SPM5 correcting for multiple comparisons. There
      was an incremental increase in response time among the study groups (healthy
      controls<first-degree relatives<schizophrenia) with no differences in accuracy
      for encoding. Response time for retrieval was significantly increased in
      schizophrenia subjects compared to healthy controls with no difference in
      accuracy. Although there were no significant differences in BOLD responses for
      the encoding task, we noted increased BOLD response to retrieval in the
      prefrontal regions (Brodmann areas 9 and 8), thalamus and insula among the
      schizophrenia subjects compared to healthy controls, and first-degree relatives.
      Familial risk for schizophrenia may be associated with qualitatively similar but
      quantitatively milder abnormalities in visual episodic memory retrieval but not
      for encoding in the prefrontal cortex and thalamus.

PMID- 22992491
TI  - Rostral-caudal gradients of abstraction revealed by multi-variate pattern
      analysis of working memory.
AB  - The lateral frontal cortex (LFC) is thought to represent contextual and rule
      based information that allows adaptive behavior according to circumstance. Recent
      progress has suggested that the representations of the LFC vary along its rostral
      caudal axis with more abstract, higher level representations associated with
      rostral areas of the LFC and more concrete, lower level representations
      associated with caudal areas of the LFC. Here, we investigated this proposal.
      Subjects responded to stimuli based upon a nested series of contextual cues
      stored in working memory (WM) while being scanned with fMRI. Higher level context
      cues denoted an abstract rule set while lower level context cues provided more
      concrete information. Using multi-variate pattern analysis (MVPA), we found
      varying forms of representation along the rostral-caudal axis of the LFC
      depending on the type of information stored in WM. Rostral areas of frontal
      cortex in the lateral orbitofrontal cortex (OFC) represented the higher level
      context, but not more concrete information, and only when more concrete
      information was unavailable. Mid-level areas in the mid-dorsolateral prefrontal
      cortex (DLPFC) and inferior frontal junction (IFJ) represented more concrete
      rules, but only when the forthcoming response could not be anticipated. By
      contrast, the dorsal premotor cortex (PMd) and primary motor cortex (M1)
      represented contextual and response information when the forthcoming response
      could be anticipated on the basis of context. Collectively, these data indicate
      that representations dedicated to higher levels of abstraction become less
      discriminating when more concrete information becomes available. These patterns
      are consistent with rostral-caudal abstraction proposals of the LFC.

PMID- 22992492
TI  - Network-specific effects of age and in-scanner subject motion: a resting-state
      fMRI study of 238 healthy adults.
AB  - Cognitive aging is accompanied by a range of structural and functional
      differences in the brain, even in the absence of neurodegenerative disease.
      Functional magnetic resonance imaging (fMRI) studies have reported increased
      bilateral activation during task performance in elderly participants compared to
      their younger counterparts, particularly in frontal regions. Alterations have
      also been observed in the functional architecture of the resting brain,
      suggesting that aging is associated with changes in the organization of the
      networks of the brain. However, previous studies have largely focused on the
      default mode network, and little is known about the effects of age on other
      resting state-networks (RSNs). The aim of the present study was to investigate
      age-differences in resting state functional connectivity (RSFC) using fMRI data
      obtained during rest from 238 healthy participants aged 21-80 years. Using
      independent component analysis (ICA) and dual-regression, the results revealed
      age-related increases in RSFC across a range of RSNs, including task-positive
      networks in frontal and parietal regions. In contrast, age-related reductions in
      the default mode network and occipital visual networks were observed.
      Furthermore, whereas the effects of age on the various RSNs were found
      independent of age-related decreases in gray matter volume, sex and subject
      motion, we report strong positive and widespread effects of estimated subject
      motion on the RSFC across RSNs. The results provide support for the notion of
      network-specific effects in aging, manifested as increased tonic activation of
      task-positive networks, supporting higher-order cognitive functions and cognitive
      control, along with reduced task-negative default mode network and sensory visual
      networks during rest. The present results also corroborate recent evidence of
      strong influence of subject motion on estimated functional connectivity measures
      and strongly suggest that studies using RSFC measures as imaging phenotypes
      should adjust for individual differences in in-scanner subject motion.

PMID- 22992494
TI  - Watching dogs chase their tails to understand OCD.

PMID- 22992495
TI  - Easier estimation of an individual's 'body time'.

PMID- 22992497
TI  - Robot allows neuroscientists to access brain cells.

PMID- 22992498
TI  - A computational view of sea urchin development.

PMID- 22992501
TI  - The tale of the Watanabe rabbit.

PMID- 22992502
TI  - Response to protocol review scenario: first do no harm.

PMID- 22992503
TI  - A standoff in post-approval monitoring.

PMID- 22992504
TI  - Response to protocol review scenario: make a collaborative effort.

PMID- 22992505
TI  - Response to protocol review scenario: develop a collegial relationship.

PMID- 22992506
TI  - Comparison of methods to control floor contamination in an animal research
      facility.
AB  - The authors evaluated the effectiveness of adhesive mats, contamination control
      flooring, and shoe covers in decreasing the presence of microbial agents on
      animal holding room floors and footwear. Swab samples taken from animal holding
      room floors after the use of each product were compared with samples taken from
      rooms after no products were used. Swab samples were also taken from the heels
      and soles of the footwear of animal care staff before and after use of each
      product. The use of contamination control flooring or shoe covers significantly
      reduced the amount of organic material (as indicated by ATP levels measured by a
      luminometer) present on floors. Bacterial and ATP contamination of footwear was
      significantly lower after the use of shoe covers than after the use of adhesive
      mats or contamination control flooring, and the use of shoe covers led to a
      greater decrease in contamination before and after use than did use of either of
      the other two products. Although shoe covers were superior to both adhesive mats
      and contamination control flooring for decreasing contamination of animal room
      floors and footwear, facilities must take into account the contamination control
      standards required, the cost of the product, and the labor and time associated
      with product use when deciding which contamination control practices to
      implement.

PMID- 22992507
TI  - A self-assessment survey of the Institutional Animal Care and Use Committee, part
      2: structure and organizational functions.
AB  - Support for Institutional Animal Care and Use Committees (IACUCs) varies among
      those in animal use-related professions. The authors designed and carried out an
      anonymous survey to solicit opinions on the structure and organizational
      functions of IACUCs. They found that most respondents believed a single,
      institution-based IACUC was an appropriate venue for institutional approval of
      animal care and use, that their IACUCs represented their institutions'
      constituencies and that the unaffiliated IACUC members adequately represented
      their surrounding communities. Respondents believed that members came prepared
      for IACUC meetings, and a majority agreed that full committee reviews were more
      thorough than designated member reviews. The quality of veterinary care for
      animals was deemed to be very good. Participants reported that the status of the
      person submitting an animal use protocol, the perceived monetary value of a grant
      associated with a protocol and pressure for a rapid protocol review did not alter
      the quality of the protocol review. On many of the survey items, opinions of
      IACUC members differently significantly from those of non-members, and opinions
      of non-member IACUC administrators differed from those of IACUC chairpersons,
      perhaps owing to differences in responsibilities and perceived status.

PMID- 22992508
TI  - A distinguished career.

PMID- 22992509
TI  - A novel approach to dissect the abscission process in Arabidopsis.
AB  - Abscission is the consequence of a specialized layer of cells undergoing a
      complex series of molecular and biochemical events. Analysis of the specific
      molecular changes associated with abscission is hampered by contamination from
      neighboring nonseparating tissues. Moreover, studies of abscission frequently
      involve the examination of events that take place in isolated segments of tissue
      exposed to nonphysiological concentrations of ethylene or indole-3-acetic acid
      for protracted periods (more than 24 h) of time. To resolve these problems, we
      have adopted the use of a transgenic line of Arabidopsis (Arabidopsis thaliana)
      where the promoter of an abscission-specific polygalacturonase gene
      (At2g41850/ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE2) has been fused to a
      green fluorescent protein reporter. RNA was extracted from green fluorescent
      protein-tagged cells, released from abscising floral organs, and used to generate
      a complementary DNA library. This library was used to probe a microarray, and a
      population of abscission-related transcripts was studied in detail. Seven novel
      abscission-related genes were identified, four of which encode proteins of
      unknown function. Reverse transcription-polymerase chain reaction analyses and
      promoter fusions to the beta-glucuronidase reporter gene confirmed the expression
      of these genes in the abscission zone and revealed other places of expression
      during seedling development. Three of these genes were studied further by
      crossing reporter lines to the abscission mutants inflorescence deficient in
      abscission (ida) and blade-on-petiole1 (bop1)/bop2 and an IDA-overexpressing
      line. Phenotypic analysis of an At3g14380 transfer DNA insertion line indicates
      that this gene plays a functional role in floral organ shedding. This strategy
      has enabled us to uncover new genes involved in abscission, and their possible
      contribution to the process is discussed.

PMID- 22992510
TI  - Cinnamate:CoA ligase initiates the biosynthesis of a benzoate-derived xanthone
      phytoalexin in Hypericum calycinum cell cultures.
AB  - Although a number of plant natural products are derived from benzoic acid, the
      biosynthesis of this structurally simple precursor is poorly understood.
      Hypericum calycinum cell cultures accumulate a benzoic acid-derived xanthone
      phytoalexin, hyperxanthone E, in response to elicitor treatment. Using a
      subtracted complementary DNA (cDNA) library and sequence information about
      conserved coenzyme A (CoA) ligase motifs, a cDNA encoding cinnamate:CoA ligase
      (CNL) was isolated. This enzyme channels metabolic flux from the general
      phenylpropanoid pathway into benzenoid metabolism. HcCNL preferred cinnamic acid
      as a substrate but failed to activate benzoic acid. Enzyme activity was strictly
      dependent on the presence of Mg2+ and K+ at optimum concentrations of 2.5 and 100
      mM, respectively. Coordinated increases in the Phe ammonia-lyase and HcCNL
      transcript levels preceded the accumulation of hyperxanthone E in cell cultures
      of H. calycinum after the addition of the elicitor. HcCNL contained a carboxyl
      terminal type 1 peroxisomal targeting signal made up by the tripeptide Ser-Arg
      Leu, which directed an amino-terminal reporter fusion to the peroxisomes. Masking
      the targeting signal by carboxyl-terminal reporter fusion led to cytoplasmic
      localization. A phylogenetic tree consisted of two evolutionarily distinct
      clusters. One cluster was formed by CoA ligases related to benzenoid metabolism,
      including HcCNL. The other cluster comprised 4-coumarate:CoA ligases from
      spermatophytes, ferns, and mosses, indicating divergence of the two clades prior
      to the divergence of the higher plant lineages.

PMID- 22992511
TI  - Poplar wood rays are involved in seasonal remodeling of tree physiology.
AB  - Understanding seasonality and longevity is a major challenge in tree biology. In
      woody species, growth phases and dormancy follow one another consecutively. In
      the oldest living individuals, the annual cycle may run for more than 1,000
      years. So far, however, not much is known about the processes triggering
      reactivation from dormancy. In this study, we focused on wood rays, which are
      known to play an important role in tree development. The transition phase from
      dormancy to flowering in early spring was compared with the phase of active
      growth in summer. Rays from wood samples of poplar (Populus * canescens) were
      enriched by laser microdissection, and transcripts were monitored by poplar whole
      genome microarrays. The resulting seasonally varying complex expression and
      metabolite patterns were subjected to pathway analyses. In February, the
      metabolic pathways related to flower induction were high, indicating that
      reactivation from dormancy was already taking place at this time of the year. In
      July, the pathways related to active growth, like lignin biosynthesis, nitrogen
      assimilation, and defense, were enriched. Based on "marker" genes identified in
      our pathway analyses, we were able to validate periodical changes in wood samples
      by quantitative polymerase chain reaction. These studies, and the resulting ray
      database, provide new insights into the steps underlying the seasonality of
      poplar trees.

PMID- 22992512
TI  - Functional characterization of a silicon transporter gene implicated in silicon
      distribution in barley.
AB  - Silicon (Si) is a beneficial element for plant growth. In barley (Hordeum
      vulgare), Si uptake by the roots is mainly mediated by a Si channel, Low Silicon1
      (HvLsi1), and an efflux transporter, HvLsi2. However, transporters involved in
      the distribution of Si in the shoots have not been identified. Here, we report
      the functional characterization of a homolog of HvLsi1, HvLsi6. HvLsi6 showed
      permeability for Si and localized to the plasma membrane. At the vegetative
      growth stage, HvLsi6 was expressed in both the roots and shoots. The expression
      level was unaffected by Si supply. In the roots, HvLsi6 was localized in
      epidermis and cortex cells of the tips, while in the leaf blades and sheaths,
      HvLsi6 was only localized at parenchyma cells of vascular bundles. At the
      reproductive growth stage, high expression of HvLsi6 was also found in the nodes.
      HvLsi6 in node I was polarly located at the transfer cells surrounding the
      enlarged vascular bundles toward the numerous xylem vessels. These results
      suggest that HvLsi6 is involved in Si uptake in the root tips, xylem unloading of
      Si in leaf blade and sheath, and intervascular transfer of Si in the nodes.
      Furthermore, HvLsi2 was found to be localized at the parenchyma cell layer
      adjacent to the transfer cells with opposite polarity of HvLsi6, suggesting that
      the coupling of HvLsi6 and HvLsi2 is involved in the intervascular transfer of Si
      at the nodes. Si translocated via the enlarged vascular bundles is unloaded to
      the transfer cells by HvLsi6, followed by HvLsi2 to reload Si to the diffuse
      vascular bundles, which are connected to the upper part of the plant, especially
      the panicles, the ultimate Si sink.

PMID- 22992513
TI  - Proteasome-mediated turnover of Arabidopsis MED25 is coupled to the activation of
      FLOWERING LOCUS T transcription.
AB  - The Mediator complex is a greater than 1-megadalton complex, composed of about 30
      subunits and found in most eukaryotes, whose main role is to transmit signals
      from DNA-bound transcription factors to RNA Polymerase II. The proteasome is
      emerging as an important regulator of transcription during both initiation and
      elongation. It is increasing the number of cases where the proteolysis of
      transcriptional activators by the proteasome activates their function. This
      counterintuitive phenomenon was called "activation by destruction." Here, we show
      that, in Arabidopsis (Arabidopsis thaliana), PHYTOCHROME AND FLOWERING TIME1
      (PFT1), the MEDIATOR25 (MED25) subunit of the plant Mediator complex, is degraded
      by the proteasome and that proteasome-mediated PFT1 turnover is coupled to its
      role in stimulating the transcription of FLOWERING LOCUS T, the plant florigen,
      which is involved in the process of flowering induction. We further identify two
      novel RING-H2 proteins that target PFT1 for degradation. We show that MED25
      BINDING RING-H2 PROTEIN1 (MBR1) and MBR2 bind to PFT1 in yeast (Saccharomyces
      cerevisiae) and in vitro, and they promote PFT1 degradation in vivo, in a RING-H2
      dependent way, typical of E3 ubiquitin ligases. We further show that both MBR1
      and MBR2 also promote flowering by PFT1-dependent and -independent mechanisms.
      Our findings extend the phenomenon of activation by destruction to a Mediator
      subunit, adding a new mechanism by which Mediator subunits may regulate
      downstream genes in specific pathways. Furthermore, we show that two novel RING
      H2 proteins are involved in the destruction of PFT1, adding new players to this
      process in plants.

PMID- 22992515
TI  - Radioimmunotherapy of fibroblast activation protein positive tumors by rapidly
      internalizing antibodies.
AB  - PURPOSE: Fibroblast activation protein (FAP) is a serine protease that has
      emerged as a promising target for cancer therapy, either by direct abrogation of
      its proinvasive activity or by specific targeting of FAP-expressing cells with
      cytotoxic immunoconjugates. We aimed to select novel human-mouse cross-reactive
      antibodies and to test suitability for tumor therapy as radioimmunoconjugates in
      a preclinical model. EXPERIMENTAL DESIGN: Human Fab fragments that bind to human
      and murine FAP were selected from an antibody phage library. Two candidates
      (ESC11 and ESC14) were engineered into fully human IgG1 antibodies and further
      characterized. We investigated the intracellular trafficking of ESC11 and ESC14
      in live cells by confocal microscopy and analyzed the biodistribution and
      therapeutic effects of anti-FAP antibodies labeled with the beta-emitting
      radionuclide (177)Lu in a melanoma xenograft nude mouse model. Results were
      compared with vF19, a humanized variant of an anti-FAP antibody that has been
      previously used in clinical trials. RESULTS: The two antibodies bound selectively
      to both human and mouse FAP, with affinities in the low nanomolar range. Binding
      to FAP-expressing melanoma cells resulted in rapid internalization of FAP
      antibody complexes. (177)Lu-labeled ESC11 specifically accumulated in melanoma
      xenografts in vivo, with a higher tumor uptake than ESC14 and vF19.
      Radioimmunotherapy with 8 MBq (177)Lu-labeled anti-FAP antibodies delayed growth
      of established tumors, whereas (177)Lu-ESC11 extended mouse survival more
      pronounced than (177)Lu-ESC14 and (177)Lu-vF19. CONCLUSION: Our results show the
      potential of ESC11 and ESC14 as potent radioimmunoconjugates or antibody-drug
      conjugates for diagnostic and therapeutic use in patients with FAP-expressing
      tumors.

PMID- 22992514
TI  - A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC
      channels, an arachidonate-regulated store-independent Orai channel.
AB  - The Orai family of calcium channels includes the store-operated CRAC channels and
      store-independent, arachidonic acid (AA)-regulated ARC channels. Both depend on
      STIM1 for their activation but, whereas CRAC channel activation involves sensing
      the depletion of intracellular calcium stores via a luminal N terminal EF-hand of
      STIM1 in the endoplasmic reticulum (ER) membrane, ARC channels are exclusively
      activated by the pool of STIM1 that constitutively resides in the plasma membrane
      (PM). Here, the EF-hand is extracellular and unlikely to ever lose its bound
      calcium, suggesting that STIM1-dependent activation of ARC channels is very
      different from that of CRAC channels. We now show that attachment of the
      cytosolic portion of STIM1 to the inner face of the PM via an N terminal Lck
      domain sequence is sufficient to enable normal AA-dependent activation of ARC
      channels, while failing to allow activation of store-operated CRAC channels.
      Introduction of a point mutation within the Lck-domain resulted in the loss of
      both PM localization and ARC channel activation. Reversing the orientation of the
      PM-anchored STIM1 C terminus via a C-terminal CAAX-box fails to support either
      CRAC or ARC channel activation. Finally, the Lck-anchored STIM1 C-terminal domain
      also enabled the exclusive activation of the ARC channels following physiological
      agonist addition. These data demonstrate that simple tethering of the cytosolic C
      terminal domain of STIM1 to the inner face of the PM is sufficient to allow the
      full, normal and exclusive activation of ARC channels, and that the N-terminal
      regions of STIM1 (including the EF-hand domain) play no significant role in this
      activation.

PMID- 22992516
TI  - Targeting the PI3K pathway in the brain--efficacy of a PI3K inhibitor optimized
      to cross the blood-brain barrier.
AB  - PURPOSE: Glioblastoma (GBM), the most common primary brain tumor in adults,
      presents a high frequency of alteration in the PI3K pathway. Our objectives were
      to identify a dual PI3K/mTOR inhibitor optimized to cross the blood-brain barrier
      (BBB) and characterize its brain penetration, pathway modulation in the brain and
      efficacy in orthotopic xenograft models of GBM. EXPERIMENTAL DESIGN:
      Physicochemical properties of PI3K inhibitors were optimized using in silico
      tools, leading to the identification of GNE-317. This compound was tested in
      cells overexpressing P-glycoprotein (P-gp) or breast cancer resistance protein
      (BCRP). Following administration to mice, GNE-317 plasma and brain concentrations
      were determined, and phosphorylated biomarkers (pAkt, p4EBP1, and pS6) were
      measured to assess PI3K pathway suppression in the brain. GNE-317 efficacy was
      evaluated in the U87, GS2, and GBM10 orthotopic models of GBM. RESULTS: GNE-317
      was identified as having physicochemical properties predictive of low efflux by P
      gp and BCRP. Studies in transfected MDCK cells showed that GNE-317 was not a
      substrate of either transporter. GNE-317 markedly inhibited the PI3K pathway in
      mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6
      hour postdose. GNE-317 was efficacious in the U87, GS2, and GBM10 orthotopic
      models, achieving tumor growth inhibition of 90% and 50%, and survival benefit,
      respectively. CONCLUSIONS: These results indicated that specific optimization of
      PI3K inhibitors to cross the BBB led to potent suppression of the PI3K pathway in
      healthy brain. The efficacy of GNE-317 in 3 intracranial models of GBM suggested
      that this compound could be effective in the treatment of GBM.

PMID- 22992518
TI  - Evaluation of low density polyethylene and nylon for delivery of synthetic
      mosquito attractants.
AB  - BACKGROUND: Synthetic odour baits present an unexploited potential for sampling,
      surveillance and control of malaria and other mosquito vectors. However,
      application of such baits is impeded by the unavailability of robust odour
      delivery devices that perform reliably under field conditions. In the present
      study the suitability of low density polyethylene (LDPE) and nylon strips for
      dispensing synthetic attractants of host-seeking Anopheles gambiae mosquitoes was
      evaluated. METHODS: Baseline experiments assessed the numbers of An. gambiae
      mosquitoes caught in response to low density polyethylene (LDPE) sachets filled
      with attractants, attractant-treated nylon strips, control LDPE sachets, and
      control nylon strips placed in separate MM-X traps. Residual attraction of An.
      gambiae to attractant-treated nylon strips was determined subsequently. The
      effects of sheet thickness and surface area on numbers of mosquitoes caught in MM
      X traps containing the synthetic kairomone blend dispensed from LDPE sachets and
      nylon strips were also evaluated. Various treatments were tested through
      randomized 4 * 4 Latin Square experimental designs under semi-field conditions in
      western Kenya. RESULTS: Attractant-treated nylon strips collected 5.6 times more
      An. gambiae mosquitoes than LDPE sachets filled with the same attractants. The
      attractant-impregnated nylon strips were consistently more attractive (76.95%; n
      = 9,120) than sachets containing the same attractants (18.59%; n = 2,203),
      control nylon strips (2.17%; n = 257) and control LDPE sachets (2.29%; n = 271)
      up to 40 days post-treatment (P < 0.001). The higher catches of mosquitoes
      achieved with nylon strips were unrelated to differences in surface area between
      nylon strips and LDPE sachets. The proportion of mosquitoes trapped when
      individual components of the attractant were dispensed in LDPE sachets of
      optimized sheet thicknesses was significantly higher than when 0.03 mm-sachets
      were used (P < 0.001). CONCLUSION: Nylon strips continuously dispense synthetic
      mosquito attractants several weeks post treatment. This, added to the superior
      performance of nylon strips relative to LDPE material in dispensing synthetic
      mosquito attractants, opens up the opportunity for showcasing the effectiveness
      of odour-baited devices for sampling, surveillance and control of disease
      vectors.

PMID- 22992519
TI  - A single-atom electron spin qubit in silicon.
AB  - A single atom is the prototypical quantum system, and a natural candidate for a
      quantum bit, or qubit--the elementary unit of a quantum computer. Atoms have been
      successfully used to store and process quantum information in electromagnetic
      traps, as well as in diamond through the use of the nitrogen-vacancy-centre point
      defect. Solid-state electrical devices possess great potential to scale up such
      demonstrations from few-qubit control to larger-scale quantum processors.
      Coherent control of spin qubits has been achieved in lithographically defined
      double quantum dots in both GaAs (refs 3-5) and Si (ref. 6). However, it is a
      formidable challenge to combine the electrical measurement capabilities of
      engineered nanostructures with the benefits inherent in atomic spin qubits. Here
      we demonstrate the coherent manipulation of an individual electron spin qubit
      bound to a phosphorus donor atom in natural silicon, measured electrically via
      single-shot read-out. We use electron spin resonance to drive Rabi oscillations,
      and a Hahn echo pulse sequence reveals a spin coherence time exceeding 200 us.
      This time should be even longer in isotopically enriched (28)Si samples. Combined
      with a device architecture that is compatible with modern integrated circuit
      technology, the electron spin of a single phosphorus atom in silicon should be an
      excellent platform on which to build a scalable quantum computer.

PMID- 22992522
TI  - Evolution: How the unicorn got its horn.

PMID- 22992520
TI  - The oyster genome reveals stress adaptation and complexity of shell formation.
AB  - The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but
      genomically poorly explored phyla, the Mollusca. Here we report the sequencing
      and assembly of the oyster genome using short reads and a fosmid-pooling
      strategy, along with transcriptomes of development and stress response and the
      proteome of the shell. The oyster genome is highly polymorphic and rich in
      repetitive sequences, with some transposable elements still actively shaping
      variation. Transcriptome studies reveal an extensive set of genes responding to
      environmental stress. The expansion of genes coding for heat shock protein 70 and
      inhibitors of apoptosis is probably central to the oyster's adaptation to sessile
      life in the highly stressful intertidal zone. Our analyses also show that shell
      formation in molluscs is more complex than currently understood and involves
      extensive participation of cells and their exosomes. The oyster genome sequence
      fills a void in our understanding of the Lophotrochozoa.

PMID- 22992523
TI  - BATF-JUN is critical for IRF4-mediated transcription in T cells.
AB  - Interferon regulatory factor 4 (IRF4) is an IRF family transcription factor with
      critical roles in lymphoid development and in regulating the immune response.
      IRF4 binds DNA weakly owing to a carboxy-terminal auto-inhibitory domain, but
      cooperative binding with factors such as PU.1 or SPIB in B cells increases
      binding affinity, allowing IRF4 to regulate genes containing ETS-IRF composite
      elements (EICEs; 5'-GGAAnnGAAA-3'). Here we show that in mouse CD4(+) T cells,
      where PU.1/SPIB expression is low, and in B cells, where PU.1 is well expressed,
      IRF4 unexpectedly can cooperate with activator protein-1 (AP1) complexes to bind
      to AP1-IRF4 composite (5'-TGAnTCA/GAAA-3') motifs that we denote as AP1-IRF
      composite elements (AICEs). Moreover, BATF-JUN family protein complexes cooperate
      with IRF4 in binding to AICEs in pre-activated CD4(+) T cells stimulated with IL
      21 and in T(H)17 differentiated cells. Importantly, BATF binding was diminished
      in Irf4(-/-) T cells and IRF4 binding was diminished in Batf(-/-) T cells,
      consistent with functional cooperation between these factors. Moreover, we show
      that AP1 and IRF complexes cooperatively promote transcription of the Il10 gene,
      which is expressed in T(H)17 cells and potently regulated by IL-21. These
      findings reveal that IRF4 can signal via complexes containing ETS or AP1 motifs
      depending on the cellular context, thus indicating new approaches for modulating
      IRF4-dependent transcription.

PMID- 22992524
TI  - Compensatory dendritic cell development mediated by BATF-IRF interactions.
AB  - The AP1 transcription factor Batf3 is required for homeostatic development of
      CD8alpha(+) classical dendritic cells that prime CD8 T-cell responses against
      intracellular pathogens. Here we identify an alternative, Batf3-independent
      pathway in mice for CD8alpha(+) dendritic cell development operating during
      infection with intracellular pathogens and mediated by the cytokines interleukin
      (IL)-12 and interferon-gamma. This alternative pathway results from molecular
      compensation for Batf3 provided by the related AP1 factors Batf, which also
      functions in T and B cells, and Batf2 induced by cytokines in response to
      infection. Reciprocally, physiological compensation between Batf and Batf3 also
      occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF
      factors is based on the shared capacity of their leucine zipper domains to
      interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene
      activation. Conceivably, manipulating this alternative pathway of dendritic cell
      development could be of value in augmenting immune responses to vaccines.

PMID- 22992526
TI  - Quantum computation: Spinning towards scalable circuits.

PMID- 22992525
TI  - Severe stress switches CRF action in the nucleus accumbens from appetitive to
      aversive.
AB  - Stressors motivate an array of adaptive responses ranging from 'fight or flight'
      to an internal urgency signal facilitating long-term goals. However, traumatic or
      chronic uncontrollable stress promotes the onset of major depressive disorder, in
      which acute stressors lose their motivational properties and are perceived as
      insurmountable impediments. Consequently, stress-induced depression is a
      debilitating human condition characterized by an affective shift from engagement
      of the environment to withdrawal. An emerging neurobiological substrate of
      depression and associated pathology is the nucleus accumbens, a region with the
      capacity to mediate a diverse range of stress responses by interfacing limbic,
      cognitive and motor circuitry. Here we report that corticotropin-releasing factor
      (CRF), a neuropeptide released in response to acute stressors and other arousing
      environmental stimuli, acts in the nucleus accumbens of naive mice to increase
      dopamine release through coactivation of the receptors CRFR1 and CRFR2.
      Remarkably, severe-stress exposure completely abolished this effect without
      recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine
      release in the nucleus accumbens is accompanied by a switch in the reaction to
      CRF from appetitive to aversive, indicating a diametric change in the emotional
      response to acute stressors. Thus, the current findings offer a biological
      substrate for the switch in affect which is central to stress-induced depressive
      disorders.

PMID- 22992528
TI  - Echocardiography and cardiac resynchronization therapy in children and patients
      with congenital heart disease.
AB  - Cardiac resynchronization therapy (CRT) has been shown to improve mortality and
      morbidity in adults with refractory heart failure and prolonged QRS-duration.
      Recent research data suggest that the therapeutic benefit is related to the
      effect of CRT on interventricular and intraventricular dyssynchrony associated
      with electrical dyssynchrony. However, around 30-40% of the patients do not
      respond to CRT when device implantation is based only on QRS-duration. It was
      hoped that improved description of mechanical dyssynchrony using imaging
      techniques, might result in improved identification of patients who could benefit
      from CRT. Different methods have been proposed but a recent multicenter
      prospective echocardiographic study (PROSPECT) was disappointing. Applying adult
      criteria for CRT treatment to children and adults with acquired and congenital
      heart disease is even more challenging due to the age-dependency of QRS-duration
      and the wide variety of underlying diseases including different ventricular
      morphology that can result in heart failure. In this review we will overview the
      adult and pediatric data of CRT treatment and propose a mechanistic approach that
      could potentially be helpful in trying to identify those patients who might
      benefit from the treatment.

PMID- 22992527
TI  - Genomic analysis of a key innovation in an experimental Escherichia coli
      population.
AB  - Evolutionary novelties have been important in the history of life, but their
      origins are usually difficult to examine in detail. We previously described the
      evolution of a novel trait, aerobic citrate utilization (Cit(+)), in an
      experimental population of Escherichia coli. Here we analyse genome sequences to
      investigate the history and genetic basis of this trait. At least three distinct
      clades coexisted for more than 10,000 generations before its emergence. The
      Cit(+) trait originated in one clade by a tandem duplication that captured an
      aerobically expressed promoter for the expression of a previously silent citrate
      transporter. The clades varied in their propensity to evolve this novel trait,
      although genotypes able to do so existed in all three clades, implying that
      multiple potentiating mutations arose during the population's history. Our
      findings illustrate the importance of promoter capture and altered gene
      regulation in mediating the exaptation events that often underlie evolutionary
      innovations.

PMID- 22992529
TI  - Tetralogy of Fallot: fetal diagnosis to surgical correction.
AB  - Tetralogy of Fallot is one of the most common forms of cyanotic congenital heart
      disease. The diagnosis consists of four main anatomic features: a large
      ventricular septal defect (anterior malaligned), overriding aorta, right
      ventricular outflow obstruction and right ventricular hypertrophy. The refinement
      of fetal screening and echocardiography has led to an increase in prenatal
      diagnosis. Prenatal diagnosis along with the recognition of extracardiac
      anomalies and genetic abnormalities, including 22q11 deletion, sets the framework
      for prenatal counseling and can help predict the postnatal course and surgical
      repair. After birth, the degree of cyanosis and the presence of other
      extracardiac and cardiac abnormalities will direct the timing of surgical repair.
      Full surgical repair within the first year of life, either primary or after a
      palliative procedure, is the mainstay of therapy. Our understanding of the
      consequences of prior era surgeries and the detrimental effects of long standing
      pulmonary insufficiency has led to newer surgical and interventional techniques.
      Tetralogy of Fallot is a lifelong disease that requires careful follow up through
      adulthood with the potential for additional surgical and interventional
      procedures later in life.

PMID- 22992531
TI  - Functional pain in hospitalised and school children.
AB  - AIM: Aim of the study was to recognise the role of psychological disagreement in
      children and adolescents suffering from functional pain. METHODS: Two groups of
      children, adolescents and their parents were interviewed: group H (hospitalized
      patients), group S (students, at school). Suitable investigations excluded
      organic lesions. The following data were analysed: 1) presence of pain in
      relation with: i) sex and age; ii) relation with parents, brothers, other
      relatives, schoolfellows; 2) efficacy of possible treatments. RESULTS: Group H:
      194 patients, median age 10 years; 134 referred pain: 62 out of 92 males and 72
      out of 102 females; location of pain: abdomen, limbs, head, back. Family
      disagreements: 36, functional pain 32; schoolfellows disagreements 114,
      functional pain 79. Correlations of pain with sex, increasing age, family and
      schoolfellows disagreements: non statistically significant. Group S: 246
      students, median age: 13 years; 188 referred pain: 78 out of 118 males and 110
      out of 128 females; pain was statistically more frequent in females, it increased
      with age. Location of pain: limbs, abdomen, head, back. Family disagreements: 31,
      functional pain 28, schoolfellows disagreements 140, functional pain 114.
      Correlations of pain with family and schoolfellows disagreements: non
      statistically significant. Several parents gave answers which were different from
      their children's. Pharmacological and dietary interventions failed to obtain
      regression of pain. CONCLUSION: In both groups, the referred disagreements were
      not statistically different among children with functional pain and those without
      pain; such psychological distress was not the only factor causing functional
      pain. The empiric treatment adopted was inefficacious.

PMID- 22992532
TI  - [Donors' personal profile in Tuscany's network of milk banks].
AB  - AIM: An investigation on human milk donors among the milk banks of Tuscany's
      network was carried out. Milk banks select, collect, check, process, store and
      deliver human milk, whose donors should have certain physical and psychological
      well-being features. The aim of the study was to describe a personal and social
      profile of milk donors. METHODS: The study included a sample of 100 milk donors
      and a sample of 100 non-milk donor mothers; a questionnaire that collected data
      about mothers' general information, clinical history, pregnancy and delivery,
      weight variations, state of health, lifestyle, breastfeeding and knowledge about
      milk banks was administered to all of them. Then information about food history
      of mothers has also been collected. RESULTS: First the samples of donors were
      analysed for all variables considered. Subsequently the samples of donors were
      compared with the samples of non-donors: statistical analysis was carried out
      with chi2 test and documented significant differences between donors and non
      donors for the majority of variables considered in the questionnaire and for food
      history. CONCLUSION: Milk donors have a good state of health, and the integration
      in milk donation initiative headed towards a healthier lifestyle. It is necessary
      to promote an advertising campaign to integrate social and sanitary politics,
      fitting to local socio-economical contest. Furthermore, the improvement of milk
      banks of public hospitals is necessary, as hospitals are places of major stream
      both of potential donors and newborns.

PMID- 22992530
TI  - Diagnosis and management of heart failure in the fetus.
AB  - Heart failure can be defined as the inability of the heart to sufficiently
      support the circulation. In the fetus, heart failure can be caused by a myriad of
      factors that include fetal shunting abnormalities, genetic cardiomyopathies,
      extracardiac malformations, arrhythmias and structural congenital heart disease.
      With advances in ultrasound has come the ability to characterize many complex
      conditions, previously poorly understood. Fetal echocardiography provides the
      tools necessary to evaluate and understand the various physiologies that
      contribute to heart failure in the fetus. In this review, we will explore the
      different mechanisms of heart failure in this unique patient population and
      highlight the role of fetal echocardiography in the current management of these
      conditions.

PMID- 22992533
TI  - Epilepsy in inherited metabolic disorders: a pediatric series.
AB  - AIM: Our study aims at further defining the characteristics of epilepsy in
      Inherited Metabolic Disorders (IMDs). METHODS: We reviewed the medical records of
      345 patients with IMDs followed at the Metabolic Diseases Unit of our Department
      of Pediatrics and found the presence of an epileptic syndrome in 45 cases. An
      overview is given based on various criteria such as pathogenetic background,
      seizure type, age of onset, EEG, neuroimaging data, treatability. Seizure types
      were: focal (24 patients), generalized (13 patients), febrile (3 patients), and
      hypoglycemic (8 patients with glycogenoses). Some patients presented with more
      than one type of seizures. Age of onset was mainly during the first year of life
      (N.=19), between 2 and 6 years in 13 patients, and after the 6th year in 9
      patients. RESULTS: Available EEGs showed either focal (N.=21) or generalized
      epileptiform abnormalities (N.=11); multifocal paroxysms were evident in 3
      patients while the remaining 3 patients had normal findings. Available
      neuroimages (CT/MRI) showed either normal findings (N.=6) or white matter
      abnormalities (N.=6), cerebral and/or cerebellar cortical atrophy (N.=11),
      hydrocephalus (N.=1), corpus callosum hypoplasia (N.=2), pontocerebellar
      hypoplasia (N.=1), gliosis in trigone area (N.=4). Most patients showed a
      favorable response to antiepileptic treatment (AEDs) with either complete control
      or reduced seizure frequency. CONCLUSION: IMDs are a relatively rare cause of
      epilepsy in children but their diagnosis is very important with respect to
      treatment, prognosis and genetic counselling.

PMID- 22992534
TI  - [Classification of the instrument of assessment of children between 0 and 3 years
      of age].
AB  - One of the difficulties described in epidemiological studies about
      psychopathology in children 0-3 years of age appears during the assessment phase.
      In fact, the assessment of indicators of particular difficulties in children is
      hampered by the rapid processes of transformation of behavior that cross all
      areas of child development. The aim of this article was to provide an overview as
      complete as possible of all instruments used in the assessment phase of children
      0-3 years. The literature shows a number of tools for evaluation and diagnosis of
      psychopathology that have been divided into four categories: mental development
      tests, interviews with parents, questionnaires and rating scales, evaluation of
      the parent-child assessment of specific diagnostic entities. The main features of
      each instrument are described.

PMID- 22992535
TI  - Tetralogy of Fallot variant with pulmonary atresia (pseudotruncus arteriosus) in
      a case of maternal PKU syndrome.
AB  - The authors report on a child with a rare variant of the Tetralogy of Fallot with
      pulmonary atresia also known as Pseudotruncus arteriosus, who was born by a
      mother affected by classic phenylketonuria (PKU), diet free of phenylalanine
      until the age of seven years. According to the authors, this is the first example
      of such rare variant in an offspring of maternal PKU syndrome.

PMID- 22992536
TI  - Dapsone treatment in a girl with severe chronic thrombocytopenic purpura. Does it
      work? Do not touch it!
AB  - Dapsone has been shown to be effective in treating immune thrombocytopenic
      purpura (ITP) in adults. In children the experience is limited. We describe our
      experience using dapsone in a female with refractory, symptomatic ITP who
      suffered intracranic haemorrhage and massive gastric bleeding. After treatment
      platelet counts was more than 100 x 103/MUL, and reached 1000x103/MUL.
      Discontinuation resulted in a rapid decrease in platelet counts, with severe
      intracranial haemorrhage (ICH). The recovery of dapsone led the platelets count
      to lower values. We suggest that treatment should not be discontinued in
      responders, at least in children with symptomatic ITP. Additional studies of
      dapsone in children are warranted.

PMID- 22992537
TI  - Oculo-auriculo-vertebral spectrum (OAVS) with large cerebral cyst: affinity to
      holoprosencephaly.

PMID- 22992538
TI  - Quantitative proteomic analysis of secretome of microbial consortium during saw
      dust utilization.
AB  - Proteomics analysis of lignocellulolytic proteins by lignocellulosic biomass
      degrading microbes and compatible microbial consortium is a promising approach
      that offers a new means to enzyme discovery. The abundance of proteins in complex
      secretome by microbial communities would highlight key lignocellulolytic proteins
      for lignocellulosic biorefinery. In this study, lignocellulolytic enzymes of
      potent lignin degrading basidiomycota and effective cellulolytic ascomycota
      fungal strains, and their co-cultures were analyzed using high throughput
      isobaric tag for relative and absolute quantitation (iTRAQ) technique using
      liquid chromatography tandem mass spectrometry. Protein abundances in the iTRAQ
      multiplexed samples were determined by integrating relative quantitation and
      exponentially modified protein abundance index (emPAI). The functional
      classification of the secretory proteins by individual culture and co-culture
      demonstrated 36.77% cellulolytic proteins, 13.06% hemicellulases, 14.09%
      ligninolytic proteins, 19.59% proteolytic enzymes. 7.22% hypothetical proteins
      and 6.87% cell morphogenesis proteins. The abundance of the proteins by
      individual cultures and co-cultured fungal consortium revealed that co-culturing
      of Phanerochaete chrysosporium with Trichoderma reesei QM6a and Trichoderma
      reesei Rut C30 induced the production of cellulolytic proteins and stimulated
      expression of hemicellulolytic enzymes. The hierarchical clustering of proteins
      in secretome of fungal strains and their co-cultures elucidated differential
      expressions of lignocellulolytic proteins by the microbial consortium.

PMID- 22992539
TI  - Synthesis of heteroatomic Zintl anions in liquid ammonia--the new highly charged
      [Sn4Bi4]4- and fully ordered [Sn2Bi2]2-.
AB  - The new Zintl anion [Sn(4)Bi(4)](4-), synthesized by dissolving CsSnBi in liquid
      ammonia, forms a monocapped nortricyclane-like cage. Its electron localization
      function (ELF) analysis shows evidence for 3-centre bonding. The analogous
      reaction with KSnBi results in a crystallographically fully ordered tetrahedral
      [Sn(2)Bi(2)](2-) ion.

PMID- 22992540
TI  - Immunogold labeling and X-ray fluorescence microscopy reveal enrichment ratios of
      Cu and Zn, metabolism of APP and amyloid-beta plaque formation in a mouse model
      of Alzheimer's disease.
AB  - The mechanism that triggers amyloid-beta (Abeta) fibrillation and aggregation is
      still elusive. Evidence suggests that the extensional interactions of the amyloid
      precursor protein (APP) and Abeta with transition biometals, copper (Cu) and zinc
      (Zn), may be key occurrences in the processes of Abeta aggregation and toxicity.
      By using an immunogold labeling technique combined with synchrotron radiation X
      ray fluorescence microprobe (SR-MUXRF) scanning analysis, the profiles of APP,
      Abeta42 and Cu, Zn in the brain of APP transgenic mouse with the development of
      the disease were characterized. This investigation provides visual, kinetic and
      spatial evidence of the correlation of APP and Abeta-metals in AD brain sections.
      The visual evidence demonstrates the association of metals Cu and Zn with Abeta42
      during plaque formation, which helps implicate the role of metal ion homeostasis
      in human AD pathology.

PMID- 22992541
TI  - Cascade imaging of proteolytic pathways in cancer cells using fluorescent protein
      conjugated gold nanoquenchers.
AB  - The real-time monitoring of the caspase cascade in cancer cells during apoptosis
      was performed using various caspase substrate-linked fluorescent proteins
      conjugated gold nanoparticles as a new imaging probe.

PMID- 22992542
TI  - Psychiatric syndromes in Parkinson's disease.
AB  - PURPOSE OF REVIEW: To examine progress about relevant behavioural and psychiatric
      disorders in Parkinson's disease, such as depression, apathy, psychosis, and
      impulse control disorder. RECENT FINDINGS: Several recent studies have
      characterized the phenomenology of depression in Parkinson's disease, and
      randomized controlled trials have demonstrated the efficacy of tricyclics,
      selective serotonin reuptake inhibitors and psychotherapy for depression in
      Parkinson's disease. Apathy is a valid behavioural syndrome in Parkinson's
      disease and is associated with depression and cognitive deficits. Psychosis is
      highly prevalent in the late stages of the disease, but there are few effective
      therapeutic modalities for this psychiatric condition. Impulse control disorders
      are also relatively frequent in Parkinson's disease, and are associated with
      comorbid psychiatric disorders. SUMMARY: Standardized criteria should be used to
      diagnose depression and apathy in Parkinson's disease. Psychotherapy and
      pharmacotherapy are useful treatment modalities for affective disorders in
      Parkinson's disease. Clozapine is still the most effective, albeit rarely used,
      treatment for psychosis in Parkinson's disease. Impulse control disorders are
      relatively frequent in Parkinson's disease and all patients should be screened
      for this complex disorder.

PMID- 22992543
TI  - Prevention and treatment options for postoperative delirium in the elderly.
AB  - PURPOSE OF REVIEW: To review recent findings and developments in strategies for
      prevention and treatment of postoperative delirium. RECENT FINDINGS: Current
      advances in the field include improved knowledge about predisposing and
      precipitating factors, evidence for efficacy of multicomponent prevention
      programmes, refinement of perioperative procedures, and promising pharmacological
      approaches for prophylaxis and management of postoperative delirium. SUMMARY:
      Postoperative delirium is a common and serious complication in elderly patients.
      Preoperative assessment of risk profiles and tailored multimodal prevention
      approaches proved effective and should be integrated into clinical practice.
      Despite promising recent findings, at present, the routine use of pharmacological
      prophylaxis cannot be recommended. Validated and easy-to-use bedside diagnostic
      tools are available and should be regularly applied for delirium screening in the
      first days after surgery. In patients developing delirium, causal conditions and
      contributing factors need to be identified and addressed. Whereas administration
      of antipsychotics may represent an option for symptomatic treatment, further
      studies are needed to evaluate the effects of pharmacological approaches on long
      term outcomes in elderly patients with delirium.

PMID- 22992544
TI  - Care transition interventions in mental health.
AB  - PURPOSE OF REVIEW: Addressing issues in transitioning patients from inpatient to
      outpatient care is one of the most salient themes in mental healthcare. We review
      current models and initiatives in general and mental healthcare and propose an
      intervention framework. RECENT FINDINGS: Using search terms in online databases
      and archives, we identified two broad categories of care transition
      interventions: models that have been put forward and tested in the area of
      general medical care and have potential for adaptation in mental health; and a
      more limited set of models that have been put forward and, to some extent, tested
      in the mental health context. On the basis of these categorical summaries, we
      propose nine components as core elements for interventions to address transitions
      in the mental health population more effectively. SUMMARY: This review of
      intervention models identified multiple models, trials and initiatives for care
      transition interventions for general medical populations, but few targeted
      specifically for mental health populations. We believe that proposing a
      conceptual framework specifying a core set of care transition intervention
      components can stimulate the development of interventions that specifically
      address patients with serious mental illness.

PMID- 22992545
TI  - Brain stimulation in psychiatry:  methods and magnets, patients and parameters.
AB  - PURPOSE OF REVIEW: Electromagnetic brain stimulation is performed in various ways
      in psychiatric settings for the treatment of a variety of psychiatric disorders.
      RECENT FINDINGS: Transcranial direct current stimulation is a comparatively
      simple procedure. The available results warrant optimism regarding the future of
      this therapeutic approach in psychiatry. Multicentre studies of repetitive
      transcranial magnetic stimulation demonstrate a moderate treatment effect in
      depression. Theta burst stimulation and deep brain repetitive transcranial
      magnetic stimulation represent innovative promising developments. The
      invasiveness of deep brain stimulation still causes this method to be one of the
      last resorts, even though promising results in severely disordered patients have
      been published. SUMMARY: In our view, the field of brain stimulation will be
      rapidly moving forward in the near future and will establish itself as one more
      of the 'tools of the trade' in psychiatric therapeutic practice.

PMID- 22992546
TI  - Pharmacological treatment of dementia.
AB  - PURPOSE OF REVIEW: In this article, we discuss new data on currently licensed
      drugs for dementia and novel developments in the management of neuropsychiatric
      symptoms in patients with dementia. RECENT FINDINGS: During the last years, a
      large body of evidence has been accumulated to support the use of antidementia
      medication in patients with severe Alzheimer's disease. Combination therapy with
      acetylcholinesterase inhibitors and memantine for Alzheimer's disease remains
      controversial, as controlled trials have yielded conflicting results. Memantine
      is not indicated in patients with mild Alzheimer's disease. Studies on memantine
      for Parkinson's disease dementia and dementia with Lewy bodies were inconclusive.
      In adult patients with dementia in the context of Down syndrome, memantine is not
      effective, and further studies on acetylcholinesterase inhibitors are warranted.
      There is still no treatment established for patients with vascular or
      frontotemporal dementia. The efficacy of antidepressants to treat depression
      associated with dementia is not proven. Treatment of agitation and psychosis in
      patients with dementia remains a challenge. SUMMARY: Recent systematic clinical
      reviews and new research on currently available treatment options provide
      valuable assistance for clinicians to deal with frequent clinical problems in the
      context of dementia.

PMID- 22992547
TI  - The third wave of cognitive behavioural therapies:  what is new and what is
      effective?
AB  - PURPOSE OF REVIEW: The purpose of this study was to shortly characterize the
      evolving psychotherapeutic methods summarized as 'third wave psychotherapies' and
      to review recent research on the therapeutic impact of these methods. RECENT
      FINDINGS: 'Third wave psychotherapies' comprise a heterogeneous group of
      treatments, including acceptance and commitment treatment, behavioural
      activation, cognitive behavioural analysis system of psychotherapy, dialectical
      behavioural therapy, metacognitive therapy, mindfulness-based cognitive therapy
      and schema therapy. Several randomized controlled trials, longitudinal case
      series and pilot studies have been performed during the past 3-5 years, showing
      the efficacy and effectiveness of 'third wave psychotherapies'. SUMMARY: The
      third wave of behavioural psychotherapies is an important arena of modern
      psychotherapy. It has added considerably to the spectrum of empirically supported
      treatments for mental disorders and influenced research on psychotherapy. The
      presented methods open up treatment possibilities for patient groups such as
      borderline personality disorder, chronic depression or generalized anxiety
      disorder that had received only little specific attention in the past. The
      available evidence now allows considering all third wave treatments as
      empirically supported.

PMID- 22992548
TI  - A decade of refinement, not revolution.

PMID- 22992549
TI  - History of psychiatry and its institutions.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent English
      language literature on the history of psychiatric institutions. It considers work
      published since 2010, as well as a few important older articles that have not yet
      been reviewed in these pages. RECENT FINDINGS: Developments in the last half of
      the 20th century suggest that psychiatric historiography might finally be able to
      put the mental asylum behind it. Deinstitutionalization and the diffusion of
      professional jurisdictions seem to have consigned institutional histories to the
      methodological dustbin. But these transformations have also opened new
      perspectives on the institutional history of psychiatry and its methodologies.
      This review reflects on some of the enduring historiographic potential and
      importance of evidence drawn from institutional settings. SUMMARY: As carceral
      narratives have begun to lose their paradigmatic status within psychiatric
      historiography, a much more nuanced picture of asylum culture is becoming
      visible. The history of psychiatric institutions remains an integral and
      productive part of psychiatric historiography.

PMID- 22992550
TI  - History of social psychiatry.
AB  - PURPOSE OF REVIEW: The overview focuses on publications relating to the history
      of social psychiatry and the mental health movement, respectively. RECENT
      FINDINGS: The selected works show fundamental developments within psychiatry,
      which can be conceived in the broadest sense as sociomedical in nature. Main
      emphases are the criticism of large institutions, reform movements and
      antipsychiatric movements, the search for alternative therapeutic methods, and
      the question of the resocialization of the mentally ill. Furthermore, it is
      important to demonstrate the influences of other scientific disciplines. SUMMARY:
      Although social psychiatric approaches can be discerned as early as in the 19th
      century, the focus of the works lies on the development of social psychiatry in
      the 20th century. Only from the 1950s onwards did social psychiatry establish
      itself as an integral part of psychiatric practice and later of research.
      Accordingly, the main focus of the studies is on the development after the Second
      World War, not least because processes that began at that time have not yet been
      concluded. Happily, a trend is apparent in this respect: the one-sided view of
      physicians and their actions is being increasingly complemented by further
      professional groups and is consequently broadened by important dimensions.

PMID- 22992551
TI  - Values-based practice in mental health and psychiatry.
AB  - PURPOSE OF REVIEW: Values-based practice (VBP) challenges traditions of clinical
      practice and moral decision-making and the literature published over the last 18
      months demonstrates a growing momentum for its use. RECENT FINDINGS: The VBP
      model has become part of the narrative of health and social care practice. It
      features in a range of publications and has been subject to philosophical
      analysis in relation to its theoretical rigour, and applied to clinical practice
      through education and training, implementation in the field and policy
      development. From a philosophical perspective the model faces several challenges;
      from a practice perspective it is welcomed as a necessary partner to Evidence
      Based Practice. Both perspectives suggest VBP requires significant adjustment to
      professional ideas of good practice, expectations of the clinician service user
      relationship and notions of what constitutes good care. SUMMARY: VBP is both a
      solution and a problem for clinicians. Whether VBP is seen as providing a much
      needed clinical skill for working with the complexity of mental health and
      psychiatry which is steeped in values or a solution to a dominant sociopolitical
      neoliberal ideology demand for choice and personalization of care, VBP will
      require clinicians to make personal changes to their values base that reach to
      the depths of their professional identity.

PMID- 22992552
TI  - Recovery:  conceptual and ethical aspects.
AB  - PURPOSE OF REVIEW: To examine recent publications on implications of recovery for
      the provision of mental health services. RECENT FINDINGS: Predominantly, the
      concept of recovery, implications for professional mental health services, and
      the impact of peer workers on the provision of healthcare are discussed. SUMMARY:
      Recovery in the context of mental health issues refers to multiple dimensions of
      the individual's development. According to recent publications, the dimension of
      an individual journey, measurable through subjective parameters and accounts, is
      complementary to the traditional objectives of symptom reduction, improvement of
      functioning, and social inclusion. To foster recovery orientation in mental
      health services subjective measures should be included in clinical practice,
      research, and teaching. Moreover, services striving to support recovery need to
      implement strategies in terms of policy, concepts, structures, and professional
      attitude. This challenging paradigm shift is claimed to be supported by the
      integration of peer workers with own lived experience in the provision of mental
      healthcare. Some exponents of the social recovery movement criticize this recent
      international development to implement recovery into traditional services, as it
      would uphold the established structures of power and control. Questions of
      impaired legal capacity, involuntary admissions and risk assessment related to
      recovery are rarely discussed.

PMID- 22992553
TI  - History, philosophy and practical psychiatry:  neither gap nor contradiction, but
      mutual enrichment.

PMID- 22992554
TI  - Streptococcus anginosus group disseminated infection: case report and review of
      literature.
AB  - Streptococcus anginosus group is widely known for its ability to cause invasive
      pyogenic infections. There are very few reports of disseminated infections
      sustained by members of this streptococcal group. We report a case of a highly
      disseminated infection and analyse previous literature reports. Disseminated
      pyogenic infection has been defined as an infection affecting two or more of the
      following organs/systems: central nervous system, lung, liver and spleen. We
      performed a PubMed search using the terms: S. milleri, S. anginosus, brain
      abscess, pulmonary abscess, hepatic abscess, spleen abscess. We reviewed 12 case
      reports including the one presented in this paper. Underlying conditions such as
      dental infections, malignancy, gastrointestinal and respiratory tract disease
      accounted for 42% of cases. No definite endocarditis was encountered, even though
      positive blood cultures were found in 67% of patients. Concomitant brain-liver,
      brain-lung and brain-spleen involvement occurred in 50%, 42% and 8% of cases
      respectively. Ninety-one percent (91%) of patients were treated with beta
      lactams, and surgical procedures were performed in 67% of patients. Infections
      caused by S. anginosus group members are satisfactorily treated with penicillin G
      and cephalosporins. It is very important to associate surgery to antimicrobial
      chemotherapy in order to achieve a full or nearly full clinical recovery.

PMID- 22992555
TI  - [Update on diabetic foot infections].
AB  - Diabetes is one of the most common non-transmitted disease and currently 346
      million people are affected in the world. According to the World Health
      Organization about 15% of diabetic patients develop a foot ulcer in  need of
      medical care. Infection is a serious complication and in the western world it is
      the major responsible cause of lower limb amputation. In the 84% of cases
      amputation is the final step in the treatment of a non-healing foot ulcer. So,
      it's clear that, in order  to reduce amputation rate,  it's important to prevent
      foot ulcer formation and  improve the treatment of lesion. In this review we
      report the most recent international literature as regards epidemiology,
      etiology, classification, diagnosis, microbiology and treatment of infected
      diabetic foot ulcers. The purpose of our work is to remark the multifactorial
      features of this pathology and the role of infectious disease specialist in a
      multidisciplinary team for the  treatment of infected diabetic foot ulcers. The
      knowledge of microbiology on one hand, and the need of a complex and long term
      antibiotic therapy on the other, point out the importance of  infectious disease
      specialist to facilitate, if possible, the healing of a infected diabetic foot
      ulcers.

PMID- 22992556
TI  - Respiratory syncytial virus infection: a decade of contributions.
AB  - Respiratory Syncytial Virus (RSV) is the main cause of acute lower respiratory
      tract infections in children under 2 years, its distribution is worldwide and
      even in very different climatic conditions, it appears to have similar features,
      certainly knowing it will produce a significant amount of infections each year.
      We present the results of a retrospective review of positive cases for RSV
      detected in the Microbiology Laboratory of the Hospital Clinico Universitario of
      Valladolid in the period between 1990 and 2000, dealing with its presentation at
      the given time with the weather variables of temperature and humidity. Every
      year, we have observed as the clustering of cases was associated with two
      outbreaks, one at the beginning and the other at the end of the year, coinciding
      with the coldest and wettest months. This pattern has been repeated every revised
      year, according to an annual rate, with the onset of the first insulation between
      the months of October and February, and of the last ending between March and
      June, showing the highest peaks of isolation during the month of February.
      Therefore, every year we observe a break or seasonal slip matching the months
      with higher temperatures and lower humidity.

PMID- 22992557
TI  - Community-acquired bloodstream infections among paediatric patients admitted to
      an Italian tertiary referral centre: a prospective survey.
AB  - Introduction. Invasive bacterial diseases continue to represent a significant
      burden in paediatric age, and the emergence of previously secondary bacteria and
      antibiotic-resistant strains requires a continuous surveillance.  Materials and
      methods. A one-year prospective survey on laboratory confirmed community-acquired
      bloodstream infections (CA-LBSIs) cases admitted to an Italian tertiary
      specialistic paediatric Hospital.  Results. Twelve cases were documented, with an
      incidence rate of 0.39/1,000 admissions to the Emergency Department, and of
      2.9/1,000 hospitalizations to general and specialized wards. Mean age at
      diagnosis was 5.2 +/- 5.9 years, with 58.3% of episodes regarding children
      younger than years. Six episodes were caused by Gram positive and six by Gram
      negative bacteria, with potential vaccine-preventable pathogens responsible of
      50% of CA-LBSIs. Empiric antibiotic therapy prescribed at admission was found
      appropriate to microbiological results in the totality of cases and administered
      for a mean time of 17.7 +/- 10.1 days. No resistant strains were found. All
      patients had a good outcome.  Conclusions. Prompt collection of samples for
      microbiological tests together with the rapid institution of empiric antibiotic
      therapy are essential for the correct management of CA-LBSIs in paediatric
      patients. Implementation of vaccinations against the major responsible pathogens
      remains the most important prevention strategy.

PMID- 22992558
TI  - ESBL- and MBL-mediated resistance in Acinetobacter baumannii: a global threat to
      burn patients.
AB  - Acinetobacter baumannii is an important pathogen causing infections, especially
      in burnt patients.  The aim of this study was to determine the prevalence of
      Extended Spectrum Beta-Lactamase (ESBL) and Metallo-Beta-Lactamase (MBL) in
      isolates of A. baumannii from burnt patients. One hundred-twenty-six A. baumannii
      strains were isolated  from both male and female burnt patients admitted to Burnt
      Unit in Motahari hospital, Tehran. The susceptibility test was done by the disk
      combination technique. Disk test and disk diffusion methods were performed to
      confirm the production of ESBL and MBL in accordance with CLSI standard
      guidelines. Twenty-one percent of ceftazidime-resistance A. baumannii isolates
      were found to be ESBL producers.  Thirty-nine percent of imipenem-resistant
      isolates produced MBL.  Prolonged hospitalization of burnt patients made an
      important contribution to the incidence of resistant bacteria. The utility of an
      accurate surveillance for ESBL and MBL in A. baumannii isolated from burnt
      patients as an important step for successful antimicrobial treatment in the
      future.

PMID- 22992559
TI  - [Experimental evaluation of the Sysmex UF-1000i for ruling out non-gonococcal
      urethritis].
AB  - Acute nongonococcal urethritis (NGU) is one of the commonest sexually transmitted
      infections affecting men and women. The diagnosis of NGU has traditionally
      required microscopic evidence of urethritis. However, a significant proportion of
      patients with urethral symptoms do not have microscopic evidence of urethritis.
      The purpose of the present study was to evaluate the analytical performance of
      the UF1000i, a recently introduced fluorescence flow cytometer intended for
      urinalysis purposes which provides new analytical features that seem particularly
      suitable for microbiological diagnostics, for ruling out NGU or predicting the
      presence of infection. The Sysmex UF1000i is a flow cytometry analyzer capable of
      quantifying a lot of particles, including bacteria (BACT) and white blood cells
      (WBCs). To evaluate the analytical performance of the UF1000i as a method for
      ruling out NGU, we examined 200 urethral smear samples, collected in a new liquid
      transport medium (Copan), and compared the UF1000i results with standard
      culture/molecular and microscopic Gram stain results. With instrument cut-off
      values of 200 BACT x 10^6/L and 500 WBCs x 10^6/L, we obtained a sensitivity of
      84%, a specificity of 82%, and a high negative predictive value (96%).
      Culture/molecular detection of pathogens remains the gold standard technique for
      the diagnosis of NGU. However, the Sysmex UF1000i is capable of improving the
      efficiency of NGU presumptive diagnosis, providing results in a few minutes, with
      a high negative predictive value and high values of sensitivity.

PMID- 22992560
TI  - [Tuberculous peritonitis: experience in Treviso from 2000 to 2010].
AB  - Peritonitis is an uncommon localization of tuberculosis in Italy; diagnosis and
      treatment are often difficult and delayed. Fifteen cases, followed by Infectious
      Diseases Department in Treviso from 2000 to 2010, are described. Mortality and
      long term complications were absent, in contrast with medical literature. The
      usefulness of steroid therapy is still uncertain.  Other sites of infection were
      present in 60 percent of patients (pulmonary TB in 47%), urging the clinician to
      examine the case promptly to determine infectiousness status.

PMID- 22992561
TI  - [Disseminated nocardiosis in a patient with haemophilia: a problem of
      differential diagnosis].
AB  - Nocardia is found worldwide in soils and dust. In immunocompromised patients the
      lungs appear to be the most common initial site of infection due to  the
      inhalation of free living organisms. Nocardia asteroides is the most commonly
      isolated pathogenic Nocardia species. Pulmonary nocardiosis may mimic
      tuberculosis, staphylococcal or mycotic infections. Disseminated disease mainly
      occurs in immunocompromised patients with underlying illnesses such as chronic
      granulomatous disease, human immunodeficiency virus (HIV) infection, in patients
      undergoing cytotoxic chemotherapy, organ transplantation or prolonged
      glucocorticoid treatment. Subcutaneous infection occurs from trauma related
      inoculation of the organism. The Authors describe a clinical case regarding a
      patient with acquired haemophilia A, admitted to the hospital because of
      disseminated nocardiosis mimicking a neoplastic disease. He recovered completely
      after the antibiotic treatment.

PMID- 22992562
TI  - Necrotizing pneumonia caused by Panton-Valentine leukocidin-producing methicillin
      susceptible Staphylococcus aureus (MSSA).
AB  - Staphylococcus aureus harboured by Panton-Valentine leukocidin (PVL) is emerging
      as a serious problem worldwide.  There has been an increase in the incidence of
      necrotizing lung infections in otherwise healthy young people with very high
      mortality rate associated with these strains. This report documents a confirmed
      case of necrotizing pneumonia due to methicillin-susceptible S. aureus (MSSA)
      harbouring Panton-Valentine leukocidin genes.  An apparently healthy 49-year old
      man was admitted to our hospital for dyspnea and he quickly developed acute
      respiratory distress syndrome. MSSA harbouring Panton-Valentine leukocidin genes
      were cultured from the abscess fluid and from multiple blood specimens.
      Aggressive antibiotic therapy was started and intensive supportive care led
      finally to a complete recovery. Rapid identification of Panton-Valentine
      leukocidin in MSSA samples should be supposed when a young, immunocompetent
      patient, develops a necrotizing pneumonia. Bactericidal antistaphylococcal
      antibiotics are recommended for the treatment as soon as possible to avoid the
      potentially devastating consequences of this kind of S. aureus.

PMID- 22992563
TI  - [Leprosy-like cutaneous presentation of Histoplasma capsulatum infection in an
      African HIV+ patient].
AB  - Histoplasma capsulatum is an opportunistic dimorphic fungus responsible for most
      often self-limiting or flu-like infections but potentially lethal in
      immunocompromised hosts. Histoplasmosis is rare in Europe. We reported a case of
      disseminated histoplasmosis in an African HIV patient with a leprosy-like primary
      cutaneous presentation and involvement of lungs, brain, limphnodes and eye. The
      therapy with liposomial B amphotericin and itraconazole led to a prompt
      resolution of the symptoms.

PMID- 22992564
TI  - Specific immunoglobulin against hepatitis C virus. Why not?

PMID- 22992565
TI  - [The Justinian plague (part two). Influence of the epidemic on the rise of the
      Islamic Empire].
AB  - The Islamic Empire started its tumultuous and rapid expansion from the year 622
      A.D. (the year of  Mohammed's Egira). This rapid growth coincided with the
      epidemic spread of the bubonic plague in the Middle East. Although a first
      epidemic event had been documented in the year 570 A.D. (pre-Islamic phase), in
      the Arabic peninsula, classically according to M.W. Dols five severe episodes of
      plague sub-epidemics are considered in the middle-eastern geographic area: the
      first occurred in 627 and 628 A.D., the fifth in  716 A.D.. Anyway, we may state
      that at the onset of Islam the geographic region including Egypt, Palestine,
      Syria, Iraq, and Iran was involved by endemic plague. In their work, on the
      ground of a literature review, the Authors describe the characteristics of the
      epidemic phenomenon, and analyze the how the plague affected the interpretation
      of Prophet's Koran and Hadits. The passive attitude demonstrated by many Muslims
      during early Islam was not shared by all believers, since others moved towards a
      more soft approach, which included the behaviour of the so called  moving aside ,
      when the contagion was of concern. The epidemic plague significantly contributed
      to the weakening of the Eastern Roman Empire, and the rapid decline of the
      Persian Empire, while during the early expansion phases of Islam, it indirectly
      favoured the nomadic Arab tribes which, moving on desert or semi-desert
      territories, succeeded in escaping the contagion more easily. Subsequently, when
      the Arab population became sedentary, after occupying the conquered cities, this
      initial advantage was significantly reduced.

PMID- 22992567
TI  - A reagentless and reusable electrochemical DNA sensor based on target
      hybridization-induced stem-loop probe formation.
AB  - We report a reagentless and reusable electrochemical DNA sensor that exploits
      competitive binding and target hybridization-induced change in the signalling
      probe conformation for robust detection of a target DNA sequence.

PMID- 22992566
TI  - Production of EV71 vaccine candidates.
AB  - Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia
      and with Coxsackie virus (CV) it is the other major causative agent of hand-foot
      mouth diseases (HFMD). Effective medications and/or prophylactic vaccines against
      HFMD are urgently needed. From a scientific (the feasibility of bioprocess,
      immunological responses and potency in animal challenge model) and business
      development (cost of goods) points of view, we in this review address and discuss
      the pros and cons of different EV71 vaccine candidates that have been produced
      and evaluated in animal models. Epitope-based synthetic peptide vaccine
      candidates containing residues 211-225 of VP1 formulated with Freund's adjuvant
      (CFA/IFA) elicited low EV71 virus neutralizing antibody responses, but were
      protective in the suckling mouse challenge model. Among recombinant EV71 subunits
      (rVP1, rVP2 and rVP3) expressed in E. coli, purified and formulated with CFA/IFA,
      only VP1 elicited mouse antibody responses with measurable EV71-specific virus
      neutralization titers. Immunization of mice with either a DNA plasmid containing
      VP1 gene or VP1 expressed in Salmonella typhimurium also generated neutralizing
      antibody responses and protected animals against a live EV71 challenge.
      Recombinant EV71 virus-like particles (rVLP) produced from baculovirus formulated
      either with CFA/IFA or alum elicited good virus neutralization titers in both
      mice and non-human primates, and were found to be protective in the suckling
      mouse EV71 challenge model. Synthetic peptides or recombinant EV71 subunit
      vaccines (rVP1 and rVLP) formulated in alum were found to be poorly immunogenic
      in rabbits. Only formalin-inactivated (FI) EV71 virions formulated in alum
      elicited cross-neutralizing antibodies against different EV71 genotypes in mice,
      rabbits and non-human primates but induced weak neutralizing responses against
      CAV16. From a regulatory, economic and market acceptability standpoint, FI-EV71
      virion vaccines are the most promising candidates and are currently being
      evaluated in human clinical trials. We further describe and analyze some new
      bioprocesses technologies that have great potential applications in EV71 vaccine
      development. This review also demonstrates the opportunities and challenges that
      the Asian vaccine industry faces today. 

PMID- 22992568
TI  - Gene expression of vitamin D metabolic enzymes at baseline and in response to
      vitamin D treatment in thyroid cancer cell lines.
AB  - The association between vitamin D and thyroid cancer is unclear. It is unknown if
      CYP27A1 or CYP2R1 are present in normal thyroid or cancer cells and there is
      limited information regarding response to treatment with vitamin D. SV40
      immortalized follicular cells (N-thy) and six thyroid cancer cell lines were
      treated with 10 uM vitamin D(3), 0.1 uM 1,25(OH)(2)D(3) or vehicle * 24 h.
      CYP27A1, CYP2R1, CYP27B1 and CYP24A1 mRNA were measured using quantitative real
      time-PCR before and after treatment. Cell proliferation was also evaluated in
      TPC1 and C643 cells after treatment with D(3), 25(OH)D(3) and 1,25(OH)(2)D(3).
      Baseline CYP27A1 and CYP27B1 mRNA were present in all cells, CYP2R1 was higher
      and CYP24A1 mRNA was lower in cancer cell lines versus N-thy. TPC1 cells had
      increased CYP24A1 mRNA levels when treated with both D(3) (3.49, p < 0.001) and
      1,25(OH)(2)D(3) (5.05, p < 0.001). C643 cells showed increased CYP24A1 mRNA
      expression when treated with 1,25(OH)(2)D(3) (5.36, p < 0.001). D(3), 25(OH)D(3)
      and 1,25(OH)(2)D(3) all significantly decreased cell proliferation in TPC1 and
      C643 cells. Overall, both cancerous and N-thy cell lines express CYP27A1 and
      CYP2R1 in addition to CYP27B1, establishing the potential to metabolize D(3) to
      1,25(OH)(2)D(3). Additionally, vitamin D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) all
      had an antiproliferative effect on two thyroid cancer cell lines.

PMID- 22992569
TI  - Intermediate closed channel state(s) precede(s) activation in the ATP-gated P2X2
      receptor.
AB  - The molecular mechanism underlying channel opening in response to agonist binding
      remains a challenging issue in neuroscience. In this regard, many efforts have
      been recently undertaken in ATP-gated P2X receptors. Among those efforts, we have
      provided evidence in the P2X2 receptor that tightening of ATP sites upon agonist
      binding induces opening of the ion channel. Here we extend our analysis to show
      that the sulfhydryl-reactive ATP analog 8-thiocyano-ATP (NCS-ATP), a potent P2X2
      agonist, when covalently labeled in the ATP-binding site at position Leu186
      likely favors the tightening mechanism, but not the channel opening mechanism.
      Our data predict the existence of intermediate or preactivation state(s) trapped
      by NCS-ATP, in which tightening of the binding site is favored while the channel
      is still closed. We propose that this (these) intermediate ATP-bound state(s)
      prime(s) channel gating in the P2X2 receptor.

PMID- 22992570
TI  - Evaluation of a neighborhood rat-management program--New York City, December 2007
      August 2009.
AB  - The Norway rat (Rattus norvegicus) is a pervasive urban rodent that can carry a
      variety of pathogens transmissible to humans, bring stress to residents of
      infested neighborhoods, damage property, and cause financial loss. Several areas
      of New York City have experienced persistent rat infestation despite a
      longstanding rat control program that employed property-level inspection and
      control measures triggered by individual citizen complaints, a common approach in
      urban areas. Recognizing the need to address conditions conducive to rat
      infestation at the community level, in 2007 the New York City Department of
      Health and Mental Hygiene launched a proactive "rat indexing" (active
      surveillance) program, using rapid inspections of properties in several Bronx
      neighborhoods with persistent rat infestation. The program included repeated,
      neighborhood-wide inspections; education and enforcement actions to promote rat
      control measures by property owners; and community outreach. Signs of rat
      infestation were noted and recorded electronically by inspectors, and records
      were analyzed to evaluate program effectiveness. After three rounds of indexing
      over a 21-month period, the percentage of properties with active rat signs (ARS)
      had declined 54%, and the percentage with severe rat infestation had declined
      58%. The indexing approach to rat control subsequently was expanded to other
      parts of the city. Indexing can be an effective control strategy in urban
      neighborhoods with persistent rat infestation.

PMID- 22992571
TI  - Chikungunya outbreak--Cambodia, February-March 2012.
AB  - Chikungunya virus (CHIKV) is an alphavirus transmitted to humans through the bite
      of infected Aedes mosquitoes. CHIKV causes fever and usually is not fatal, but
      can cause debilitating joint pains or, in rare instances, severe illness. The
      East/Central/South African strain of chikungunya has been emerging in Asia since
      2006, first in the Indian subcontinent, then Thailand. This report describes the
      characteristics of a local outbreak linked with chikungunya reemergence in a
      rural Asian setting. Sporadic cases of chikungunya were identified in Cambodia in
      2011. Antibodies to CHIKV have been detected in serum collected in Cambodia in
      2007, but the strain could not be identified for those cases (U.S. Naval Medical
      Research Unit 2, unpublished data, 2012). On March 7, 2012, several cases of rash
      with fever were reported among village residents of Trapeang Roka in Kampong Speu
      Province, Cambodia. Subsequent field investigation revealed that four of six
      blood samples from affected persons were positive for CHIKV by polymerase chain
      reaction (PCR) at U.S. Naval Medical Research Unit 2 in Phnom Penh. Investigators
      from the Cambodian Communicable Disease Control Department, National Malaria
      Center, Institut Pasteur du Cambodge (IPC), local health centers, and village
      authorities conducted a seroprevalence study of village residents on March 26 to
      gather information for response planning and control efforts. The outbreak
      affected families throughout the village, and 44.7% of the population tested had
      evidence of infection by CHIKV, which affected all age groups. Public health
      agencies and policymakers in affected and nearby unaffected areas of Asia and
      elsewhere should be alert to the potential spread and reemergence of CHIKV.

PMID- 22992572
TI  - Update on vaccine-derived polioviruses--worldwide, April 2011-June 2012.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide.
      One of the main tools used in polio eradication efforts has been the live,
      attenuated oral poliovirus vaccine (OPV). This inexpensive vaccine is
      administered easily by mouth, makes recent recipients resistant to infection by
      wild polioviruses (WPVs), and provides long-term protection against paralytic
      disease through durable humoral immunity. Nonetheless, rare cases of vaccine
      associated paralytic poliomyelitis can occur both among immunologically normal
      OPV recipients and their contacts and among persons who are immunodeficient. In
      addition, vaccine-derived polioviruses (VDPVs) can emerge to cause polio
      outbreaks in areas with low OPV coverage and can replicate for years in persons
      who are immunodeficient. This report updates previous surveillance summaries and
      describes VDPVs detected worldwide during April 2011-June 2012. In 2011, a new
      outbreak of circulating VDPVs (cVDPVs) was identified in Yemen; a second VDPV
      isolate, related to a previously reported VDPV isolate, signaled an outbreak in
      Mozambique; and VDPV circulation reemerged in Madagascar. An outbreak that began
      in Somalia in 2008 continued until December 2011. Outbreaks in Nigeria and the
      Democratic Republic of the Congo (DRC) identified in 2005 and 2008, respectively,
      continued in 2012. Niger experienced a new cVDPV importation from Nigeria in
      2011. Twelve newly identified persons in six middle-income countries were found
      to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among
      healthy persons and environmental samples in 13 countries. To prevent VDPV
      emergence and spread, all countries should maintain high vaccination coverage
      against all three poliovirus serotypes; OPV use will be discontinued worldwide
      once all WPV transmission is interrupted.

PMID- 22992573
TI  - Histoplasmosis outbreak among day camp attendees--Nebraska, June 2012.
AB  - On June 21, 2012, the Douglas County Health Department (DCHD) in Omaha, Nebraska,
      was notified of an acute respiratory illness cluster among 32 counselors at city
      sponsored day camps. Laboratory-confirmed histoplasmosis was diagnosed in one
      camp counselor. DCHD and the Nebraska Department of Health and Human Services
      (NDHHS) investigated the extent and source of the outbreak to prevent further
      infections.

PMID- 22992574
TI  - Improving the estimation of influenza-related mortality over a seasonal baseline.
AB  - BACKGROUND: Existing methods for estimation of mortality attributable to
      influenza are limited by methodological and data uncertainty. We have used
      proxies for disease incidence of the three influenza cocirculating subtypes
      (A/H3N2, A/H1N1, and B) that combine data on influenza-like illness consultations
      and respiratory specimen testing to estimate influenza-associated mortality in
      the United States between 1997 and 2007. METHODS: Weekly mortality rate for
      several mortality causes potentially affected by influenza was regressed linearly
      against subtype-specific influenza incidence proxies, adjusting for temporal
      trend and seasonal baseline, modeled by periodic cubic splines. RESULTS: Average
      annual influenza-associated mortality rates per 100,000 individuals were
      estimated for the following underlying causes of death: for pneumonia and
      influenza, 1.73 (95% confidence interval = 1.53-1.93); for chronic lower
      respiratory disease, 1.70 (1.48-1.93); for all respiratory causes, 3.58 (3.04
      4.14); for myocardial infarctions, 1.02 (0.85-1.2); for ischemic heart disease,
      2.7 (2.23-3.16); for heart disease, 3.82 (3.21-4.4); for cerebrovascular deaths,
      0.65 (0.51-0.78); for all circulatory causes, 4.6 (3.79-5.39); for cancer, 0.87
      (0.68-1.05); for diabetes, 0.33 (0.26-0.39); for renal disease, 0.19 (0.14-0.24);
      for Alzheimer disease, 0.41 (0.3-0.52); and for all causes, 11.92 (10.17-13.67).
      For several underlying causes of death, baseline mortality rates changed after
      the introduction of the pneumococcal conjugate vaccine. CONCLUSIONS: The proposed
      methodology establishes a linear relation between influenza incidence proxies and
      excess mortality, rendering temporally consistent model fits, and allowing for
      the assessment of related epidemiologic phenomena such as changes in mortality
      baselines.

PMID- 22992576
TI  - Asymmetric autocatalysis initiated by achiral nucleic acid base adenine:
      implications on the origin of homochirality of biomolecules.
AB  - Enantiomorphous crystals of adeninium dinitrate acted as the source of chirality
      in asymmetric autocatalysis producing highly enantioenriched (S)- and (R)-5
      pyrimidyl alkanols, with the absolute configurations corresponding to that of
      crystals.

PMID- 22992575
TI  - Perfluorochemicals and endometriosis: the ENDO study.
AB  - BACKGROUND: Environmental chemicals may be associated with endometriosis. No
      published research has focused on the possible role of perfluorochemicals (PFCs)
      despite their widespread presence in human tissues. METHODS: We formulated two
      samples. The first was an operative sample comprising 495 women aged 18-44 years
      scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in
      the Salt Lake City or San Francisco area, 2007-2009. The second was a population
      based sample comprising 131 women matched to the operative sample on age and
      residence within a 50-mile radius of participating clinics. Interviews and
      anthropometric assessments were conducted at enrollment, along with blood
      collection for the analysis of nine PFCs, which were quantified using liquid
      chromatography-tandem mass spectrometry. Endometriosis was defined based on
      surgical visualization (in the operative sample) or magnetic resonance imaging
      (in the population sample). Using logistic regression, we estimated odds ratios
      (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed),
      adjusting for age and body mass index, and then parity. RESULTS: Serum
      perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and
      perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in
      the operative sample; findings were moderately attenuated with parity adjustment
      (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic
      acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for
      moderate/severe endometriosis, although the odds were similarly attenuated with
      parity adjustment (OR = 1.50 and 1.86, respectively). CONCLUSIONS: Select PFCs
      were associated with an endometriosis diagnosis. These associations await
      corroboration.

PMID- 22992577
TI  - The effect of intensification with raltegravir on the HIV-1 reservoir of latently
      infected memory CD4 T cells in suppressed patients.
AB  - OBJECTIVES: The stability of the reservoir of latently infected memory CD4 T
      cells may be associated with continuous replenishment from residual HIV-1, not
      completely eliminated by otherwise successful antiretroviral therapy (ART).
      Treatment intensification could help to control residual virus and to modify the
      latent reservoir. The objective of this work is to assess the effect of
      intensifying therapy with raltegravir on the HIV-1 cell reservoir. DESIGN: A
      pilot open-label phase-II clinical trial was performed to analyze ART
      intensification with raltegravir after 48 weeks in chronically HIV-1-infected
      patients on stable ART. METHODS: We measured the number of latently infected
      memory CD4 T cells, residual viremia, 2-long terminal repeat circles, CD4/CD8 T
      cell activation, lymphocyte subpopulations, gut homing receptor, and bacterial
      translocation. RESULTS: A significant decay of HIV-1 latent reservoir was
      observed after intensification in the nine patients included (P = 0.021). No
      variation was found in either residual viremia or 2-long terminal repeat circles,
      whereas CD8 T-cell activation decreased at week 36 (P = 0.028). No differences
      were found in naive T-cell or effector memory cell counts, and the frequencies of
      gut homing receptor on activated or effector memory CD8 T cells. Bacterial
      translocation was stable, with the exception of a late decrease in
      lipopolysaccharide levels. CONCLUSIONS: In this pilot noncomparative trial,
      treatment intensification with raltegravir significantly decreased the latent
      cellular HIV-1 reservoir and CD8 T-cell activation. Despite the limitations
      inherent to trial design, our results suggest that ART intensification should be
      considered as an adjuvant strategy to eradicate HIV-1 infection.

PMID- 22992578
TI  - Alleles at rs4273729 in the chromosome 6 do not predict response to peg
      interferon-alpha and ribavirin therapy in hepatitis C virus/HIV-1-coinfected
      patients.

PMID- 22992579
TI  - Similar virologic response after initiation of triple-class antiretroviral
      therapy in primary and chronic HIV infection.

PMID- 22992580
TI  - Successful use of eltrombopag without splenectomy in refractory HIV-related
      immune reconstitution thrombocytopenia.

PMID- 22992581
TI  - Human capital contracts for global health:  a plan to increase the number of
      physicians in resource limited settings.

PMID- 22992582
TI  - Understanding excess uptake maxima for hydrogen adsorption isotherms in
      frameworks with rht topology.
AB  - For a series of metal-organic frameworks with rht topology, we study
      computationally the effect of the linker length on the surface area, pore size,
      and pore volume, relating them with the hydrogen adsorption properties. The
      results provide new insights about the excess capacities and the pressures where
      the uptake maxima in the excess isotherms occur. We found that, of the materials
      studied,  has the optimal pore volume for excess gravimetric hydrogen uptake.

PMID- 22992583
TI  - Employees' perceptions of the impact of work on health behaviours.
AB  - Research examining the impact of work on health behaviours has rarely provided a
      complete picture of the impact across health behaviours. Twenty-four employees
      were interviewed about their smoking, drinking, exercise and eating. Themes
      included the impact of the work environment, including policy, convenience and
      workplace cultural norms; business events effecting one's routine and again
      convenience and workplace cultural norms; being busy at work effecting time and
      energy for healthy behaviour; and work stress leading to health behaviours being
      used as coping responses on bad and good days. The impact of work is similar
      across health behaviours and is primarily detrimental.

PMID- 22992584
TI  - Methamphetamine use and HIV in relation to social cognition.
AB  - The relation of methamphetamine abuse and HIV infection to social cognition
      (Reading the Mind in the Eyes Task and Faux Pas Recognition Task) was examined in
      men who have sex with men (N = 56): Of the methamphetamine users (n = 29), 19
      were identified as HIV positive, and of the nonusers (n = 27), 13 were identified
      as HIV positive. Both methamphetamine use and HIV were associated with impaired
      performance on the Eyes Task (p < .05). Methamphetamine use was also associated
      with impaired performance on the Faux Pas Task (p < .05). These results link
      impaired social cognition to methamphetamine abuse and HIV infection.

PMID- 22992586
TI  - Annual variation in Internet keyword searches: Linking dieting interest to
      obesity and negative health outcomes.
AB  - This study investigated the annual variation in Internet searches regarding
      dieting. Time-series analysis was first used to examine the annual trends of
      Google keyword searches during the past 7 years for topics related to dieting
      within the United States. The results indicated that keyword searches for dieting
      fit a consistent 12-month linear model, peaking in January (following New Year's
      Eve) and then linearly decreasing until surging again the following January.
      Additional state-level analyses revealed that the size of the December-January
      dieting-related keyword surge was predictive of both obesity and mortality rates
      due to diabetes, heart disease, and stroke.

PMID- 22992585
TI  - Understanding how mothers of adolescent girls obtain information about the human
      papillomavirus vaccine: associations between mothers' health beliefs, information
      seeking, and vaccination intentions in an ethnically diverse sample.
AB  - We examined factors associated with information seeking about the human
      papillomavirus vaccine among mothers of adolescent girls by testing whether
      information seeking and vaccination intentions for their daughters are associated
      with perceived vulnerability, severity, and vaccine benefits in an ethnically
      diverse sample. Mothers (N = 256) of unvaccinated girls living in Dallas, Texas,
      were surveyed (49% Black, 29% Hispanic, and 18% White). Perceived vulnerability
      to human papillomavirus was associated with talking with others (odds ratio =
      1.71, 95% confidence interval = 1.09, 2.66) and talking with a doctor about the
      vaccine (odds ratio = 1.42, 95% confidence interval = 1.01, 1.99), and perceived
      vaccine benefits were associated with vaccination intentions (odds ratio = 2.96,
      95% confidence interval = 1.98, 4.42), but the perceived severity was not
      associated with any dependent measure. Beliefs about human papillomavirus risk
      are associated with seeking information from a doctor and interpersonal sources,
      but ethnic minorities are less likely to talk with others about the vaccine.

PMID- 22992587
TI  - Self-perceptions of well-being in professional helpers and volunteers operating
      in war contexts.
AB  - We carried out qualitative research with 61 health professionals and volunteer
      workers to explore their perceptions of their own and their clients' well-being
      in a context of political violence. We applied content analysis to identify the
      themes emerging from 8 focus group and 11 individual interviews. Participants
      were found to define the concept of well-being in terms of three key areas:
      security, participation, and development. Palestinian health providers see
      promotion of economic development and professional growth, involvement in
      political and social life, and resistance to the occupation as factors required
      to enhance well-being and quality of life for themselves and their clients.

PMID- 22992588
TI  - Membrane trafficking: extracellular space travel.

PMID- 22992589
TI  - Assembly of allosteric macromolecular switches: lessons from PKA.
AB  - Protein kinases are dynamic molecular switches that have evolved to be only
      transiently activated. Kinase activity is embedded within a conserved kinase
      core, which is typically regulated by associated domains, linkers and interacting
      proteins. Moreover, protein kinases are often tethered to large macromolecular
      complexes to provide tighter spatiotemporal control. Thus, structural
      characterization of kinase domains alone is insufficient to explain protein
      kinase function and regulation in vivo. Recent progress in structural
      characterization of cyclic AMP-dependent protein kinase (PKA) exemplifies how our
      knowledge of kinase signalling has evolved by shifting the focus of structural
      studies from single kinase subunits to macromolecular complexes.

PMID- 22992590
TI  - TGFbeta signalling in context.
AB  - The basic elements of the transforming growth factor-beta (TGFbeta) pathway were
      revealed more than a decade ago. Since then, the concept of how the TGFbeta
      signal travels from the membrane to the nucleus has been enriched with additional
      findings, and its multifunctional nature and medical relevance have relentlessly
      come to light. However, an old mystery has endured: how does the context
      determine the cellular response to TGFbeta? Solving this question is key to
      understanding TGFbeta biology and its many malfunctions. Recent progress is
      pointing at answers.

PMID- 22992593
TI  - Chromatin: Lys36 sets limits for histone exchange.

PMID- 22992591
TI  - Minimizing the damage: repair pathways keep mitochondrial DNA intact.
AB  - Mitochondrial DNA (mtDNA) faces the universal challenges of genome maintenance:
      the accurate replication, transmission and preservation of its integrity
      throughout the life of the organism. Although mtDNA was originally thought to
      lack DNA repair activity, four decades of research on mitochondria have revealed
      multiple mtDNA repair pathways, including base excision repair, single-strand
      break repair, mismatch repair and possibly homologous recombination. These mtDNA
      repair pathways are mediated by enzymes that are similar in activity to those
      operating in the nucleus, and in all cases identified so far in mammals, they are
      encoded by nuclear genes.

PMID- 22992594
TI  - DNA targeting polyaza macrobicyclic dizinc(II) complexes promoting high in vitro
      caspase dependent anti-proliferative activity against human carcinoma cancer
      cells.
AB  - A series of macrobicyclic dizinc(II) complexes [Zn(2)L(1-2)B](ClO(4))(4) (1-6)
      have been synthesized and characterized (L(1-2) are polyaza macrobicyclic
      binucleating ligands, and B is the N,N-donor heterocyclic base (viz. 2,2'
      bipyridine (bipy) and 1,10-phenanthroline (phen)). The DNA and protein binding,
      DNA hydrolysis and anticancer activity of these complexes were investigated. The
      interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic
      techniques, including absorption, fluorescence and CD spectroscopy. The DNA
      binding constant values of the complexes were found to range from 2.80 * 10(5) to
      5.25 * 10(5) M(-1), and the binding affinities are in the following order: 3 > 6
      > 2 > 5 > 1 > 4. All the dizinc(II) complexes 1-6 are found to effectively
      promote the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic
      conditions. Kinetic data for DNA hydrolysis promoted by 3 and 6 under
      physiological conditions give observed rate constants (k(obs)) of 5.56 +/- 0.1
      and 5.12 +/- 0.2 h(-1), respectively, showing a 10(7)-fold rate acceleration over
      the uncatalyzed reaction of dsDNA. Remarkably, the macrobicyclic dizinc(II)
      complexes 1-6 bind and cleave bovine serum albumin (BSA), and effectively promote
      the caspase-3 and caspase-9 dependent deaths of HeLa and BeWo cancer cells. The
      cytotoxicity of the complexes was further confirmed by lactate dehydrogenase
      enzyme levels in cancer cell lysate and content media.

PMID- 22992595
TI  - Redox tuning of cytochrome b562 through facile metal porphyrin substitution.
AB  - The biologically and nanotechnologically important heme protein cytochrome b(562)
      was reconstructed with zinc and copper porphyrins, leading to significant changes
      in the spectral, redox and electron transfer properties. The Cu form shifts the
      redox potential by +300 mV and exhibits high electron transfer, while the Zn form
      is redox inert.

PMID- 22992592
TI  - Endoplasmic reticulum-mitochondria contacts: function of the junction.
AB  - The most well-characterized organelle contact sites are those between the
      endoplasmic reticulum (ER) and mitochondria. Increased understanding is being
      gained of how ER-mitochondria contact sites are organized and which factors
      converge at this interface, some of which may provide a tethering function. The
      role of the ER-mitochondria junction in coordinating the functions of these two
      organelles is also becoming clearer, and it has been shown to be involved in the
      regulation of lipid synthesis, Ca(2+) signalling and the control of mitochondrial
      biogenesis and intracellular trafficking.

PMID- 22992596
TI  - Radical SAM enzymes in methylation and methylthiolation.
AB  - Radical S-adenosyl-l-methionine (SAM) enzymes are a large and diverse superfamily
      with functions ranging from enzyme activation through a single H atom abstraction
      to complex organic and metal cofactor synthesis involving a series of steps.
      Though these enzymes carry out a variety of functions, they share common
      structural and mechanistic characteristics. All of them contain a site
      differentiated [4Fe-4S] cluster, ligated by a CX(3)CX(2)C or similar motif, which
      binds SAM at the unique iron. The [4Fe-4S](1+) state of the cluster reductively
      cleaves SAM to produce a 5'-deoxyadenosyl radical, which serves to initiate the
      diverse reactions catalyzed by these enzymes. Recent highlights in the
      understanding of radical SAM enzymes will be presented, with a particular
      emphasis on enzymes catalyzing methylation and methythiolation reactions.

PMID- 22992597
TI  - Image quality of 320-detector row wide-volume computed tomography with diffuse
      lung diseases: comparison with 64-detector row helical CT.
AB  - OBJECTIVES: To evaluate image quality of 320-detector row wide-volume (WV)
      computed tomography (CT) compared to 64-detector row helical CT from axial images
      and coronal multiplanar reformation (MPR). METHODS: Thirty-five patients with
      diffuse lung diseases were scanned using both 320-detector row WV CT (coneXact
      and volumeXact+) and 64-detector row helical protocols. Three blinded observers
      evaluated dislocation and heterogeneity of normal structures on 3 MPR patterns
      (WV scan with coneXact, WV scan with volumeXact+, and helical scan) using a 3
      point scale from 1 (severe dislocation/heterogeneity) to 3 (no
      dislocation/heterogeneity). They also evaluated axial images of 2 scan patterns
      (WV with volumeXact+ and helical) using a 5-point scale from 1 (nondiagnostic) to
      5 (excellent). Statistical analyses were performed with a post hoc test, Wilcoxon
      signed rank test, Mann-Whitney U test, or the Kendall W test. RESULTS: The WV
      scans with the coneXact algorithm had significantly lower quality scores than the
      WV scans with the volumeXact+ algorithm and the helical scans (P < 0.01) with
      MPR. Helical scans had significantly lower quality scores than the WV scans with
      volumeXact+ for heterogeneity on the mediastinal window setting with MPR (P <
      0.01). There were no significant differences concerning total image quality of
      axial images between the WV scans with the volumeXact+ algorithm and the helical
      scans. CONCLUSIONS: The overall image quality of WV scans with the volumeXact+
      algorithm was almost comparable to that of the helical scans on the lung window
      setting, but density homogeneity with helical scans was inferior to that of the
      WV scans with the volumeXact+ algorithm on the mediastinal window setting with
      MPR.

PMID- 22992598
TI  - Low-dose computed tomography of the chest using iterative reconstruction versus
      filtered back projection:  comparison of image quality.
AB  - OBJECTIVE: The purpose of this study was to compare image quality of iterative
      reconstruction (IR) to filtered back projection (FBP) in low-dose computed
      tomography of the chest. METHODS: Forty-three consecutive patients were
      retrospectively enrolled. Eight series of images were reconstructed using FBP and
      7 levels of IR in each subject. Image noise, signal-to-noise ratio (SNR), and SNR
      improvement were measured. Two radiologists evaluated subjective artifact, image
      artificiality, and subjective overall image quality with 4- or 5-point scales.
      RESULTS: Iterative reconstruction showed significantly lower image noise (135.5
      +/- 36.6 vs 219.9 +/- 40.9) and higher SNR (0.36 +/- 0.12 vs 0.21 +/- 0.05) than
      FBP (P < 0.001). Signal-to-noise ratio improvement was 72.4% +/- 44.9%.
      Subjective artifact of FBP was significantly higher than IR images (P < 0.001).
      Image artificiality of IR was significantly higher than that of FBP (P < 0.001).
      Overall, subjective image quality was poor in FBP and acceptable or good in IR.
      CONCLUSIONS: With the use of IR, low-dose computed tomography of the chest would
      achieve less image noise and better image quality compared to the FBP.

PMID- 22992599
TI  - Multifocal micronodular pneumocyte hyperplasia:  computed tomographic appearance
      and follow-up in tuberous sclerosis complex.
AB  - OBJECTIVE: To characterize pulmonary nodules in patients with tuberous sclerosis
      complex (TSC) using computed tomography. METHODS: We retrospectively reviewed
      chest computed tomographic images of 73 patients with TSC (22 males and 51
      females; mean +/- SD age, 31.5 +/- 13.2 years; range, 13.8-63.5 years). RESULTS:
      Multiple pulmonary nodules were identified in 42 (58%) of 73 patients (mean +/-
      SD size, 6.6 +/- 3.0 mm; range, 2-14 mm). Solid nodules were present in 11 (26%)
      of 42 patients, ground-glass nodules were present in 3 (7%) of 42 patients, and
      both solid and ground-glass nodules were present in 28 (67%) of 42 patients. The
      presence of multiple nodules was independent of sex and lymphangioleiomyomatosis.
      Follow-up images were available for 22 patients with multiple nodules (mean +/-
      SD follow-up, 2.0 +/- 1.1 years; range, 0.9-4.9 years), none of whom had change
      in nodule size or number. CONCLUSIONS: Most men and women with TSC have multiple
      pulmonary nodules, which likely represent multifocal micronodular pneumocyte
      hyperplasia in the absence of known predisposing factors.

PMID- 22992600
TI  - Experimental study of detection of nodules showing ground-glass opacity and
      radiation dose by using anthropomorphic chest phantom: digital tomosynthesis and
      multidetector CT.
AB  - OBJECTIVE: The purpose of this study was to compare chest digital tomosynthesis
      (DTS) and multidetector computed tomography (MDCT) for the detection of pulmonary
      ground-glass opacity (GGO) nodules and estimation of radiation dose using an
      anthropomorphic chest phantom and simulated nodules. MATERIALS AND METHODS: A
      male anthropomorphic chest phantom equipped with thermoluminescent dosimeters and
      simulated pulmonary nodules showing GGO was scanned by MDCT and DTS. The organic
      radiation doses were recorded and converted into effective doses. The density,
      diameter, and position of pulmonary nodules were reviewed; and the sensitivities
      of nodule detection were compared using the Fisher exact test. The radiation dose
      levels of DTS and MDCT were compared using paired t tests. RESULTS: The
      sensitivities of nodule detection by DTS and MDCT were 60% and 80%, respectively
      (P < 0.05), whereas the sensitivities of detection of -630-Hounsfield unit (HU)
      GGO nodules were 73.3% and 86.7%, respectively (P > 0.05), and the detection
      sensitivities of 5- and 8-mm diameter -800 HU GGO nodules were 33.3% and 58.3%,
      respectively (P < 0.05). The effective doses of DTS and MDCT were 0.65 and 7.71
      mSv, respectively, and the mean effective dose of DTS for the chest was 91.6%
      lower than that of MDCT. CONCLUSION: Multidetector computed tomography is
      preferable to DTS for the detection of GGO pulmonary nodules. Although the
      detection sensitivities of DTS and MDCT were similar for the nodules with a
      density of -630 HU, the detection sensitivity of MDCT was significantly superior
      to that of DTS for the 5- and 8-mm nodules with a density of -800 HU. The mean
      effective dose of DTS to the chest was significantly lower than that of MDCT.

PMID- 22992602
TI  - Recurrent pulmonary embolism due to echinococcosis secondary to hepatic surgery
      for hydatid cysts.
AB  - We describe the case of a 53-year-old man with recurrent pulmonary embolism due
      to intra-arterial cysts from Echinococcus. Both the patient's medical history and
      the computed tomographic (CT) scan abnormalities led to the diagnosis. The CT
      scan, performed during hospitalization in our ward, showed cystic masses in the
      left main pulmonary artery and in the descending branch of the right pulmonary
      artery. Within cystic masses, thin septa were visible, giving a chambered
      appearance, which was suggestive of a group of daughter cysts. In the past, our
      patient underwent multiple operations for recurring echinococcal cysts of the
      liver. After the last intervention, 4 years earlier, his postoperative course was
      complicated by pulmonary embolism: a CT scan showed a filling defect in the
      descending branch of the right pulmonary artery, which was caused by the same
      cystic mass as 4 years later, although smaller. This mass, not properly treated,
      increased in diameter. Moreover, after 4 years, there has been a new episode of
      embolism, which involved the left main pulmonary artery. This is the first case
      in which there are repeated episodes of pulmonary embolism echinococcosis after
      hepatic surgery for removal of hydatid cysts.

PMID- 22992601
TI  - Spontaneously healed asymptomatic pulmonary tuberculosis: prevalence of airflow
      obstruction, and correlation between high-resolution CT findings and pulmonary
      function tests.
AB  - RATIONALE AND OBJECTIVES: We investigated the relationships between spontaneously
      healed asymptomatic pulmonary tuberculosis (SHAPTB), airflow obstruction (AFO),
      and high-resolution computed tomography (HRCT) findings. MATERIALS AND METHODS:
      We selected 82 participants with SHAPTB diagnosed by interferon-gamma release
      assay and 8044 with normal chest radiographs (CXR). We applied a CT scoring
      system for the extent of tuberculous sequelae to correlate the HRCT findings with
      pulmonary function test. We compared the AFO prevalence between subjects with and
      without SHAPTB. RESULTS: The subjects with SHAPTB diagnosed by interferon-gamma
      release assay had a significantly higher prevalence of AFO (13.4% [11/82]) than
      those with normal CXR (7.4% [595/8044]). The important HRCT findings that
      correlated with AFO were the number of lung segments with TB sequelae and the CT
      score for emphysema. CONCLUSION: The subjects with SHAPTB had a higher AFO
      prevalence than those with normal CXR, and the important HRCT findings correlated
      with AFO were the extent of tuberculous sequelae and emphysema.

PMID- 22992603
TI  - Dynamic computed tomographic pulmonary angiography as a problem-solving tool in
      indeterminate computed tomographic angiography for pulmonary embolism.
AB  - OBJECTIVE: Computed tomographic pulmonary angiography may be indeterminate in
      regions of slow arterial flow because of underlying lung disease. In this case,
      dynamic computed tomographic angiography of the pulmonary vasculature (dynamic
      CTPA) was used to confirm flow variation within the pulmonary arteries in regions
      of pulmonary fibrosis and excluded pulmonary embolism. CONCLUSIONS: Dynamic CTPA
      successfully demonstrates flow variation within the pulmonary arteries and may be
      a useful adjunct to exclude pulmonary embolism in CTPA cases with questionable
      arterial filling defects.

PMID- 22992604
TI  - Isolated celiac and superior mesenteric artery dissection identified with MDCT:
      imaging findings and clinical course.
AB  - OBJECTIVE: Isolated celiac or superior mesenteric artery (SMA) dissection is a
      rare entity in the absence of aortic dissection. Our objective was to detail
      imaging and clinical course of celiac and or SMA dissections. METHODS: We
      conducted a retrospective search from 2004 to 2010 using "celiac and/or SMA
      dissection" keywords. Analysis of medical record and imaging at diagnosis and
      follow-up was performed. Dissections for any reason without aortic dissection
      were included. RESULTS: Twenty-four celiac and 18 SMA dissections were detected
      in 38 patients. One third of the dissections diagnosed with interactive
      multiplanar reconstruction/maximum intensity projection (MIP)/3-dimensional (3D)
      rendering were missed on standard imaging planes. No patients had bowel ischemia
      or died. Eighty-four percent of the patients were observed, 2 patients received
      anticoagulation, 2 patients received surgical repair, and 3 patients received
      stenting. Twenty-three of 25 cases treated with observation exhibited no change
      or improvement/resolution (2/25) with 20.9-month mean follow-up. CONCLUSION: Most
      isolated celiac and SMA dissections were asymptomatic/incidental, supporting
      observation and surveillance with intervention reserved for vascular compromise.
      Interactive multiplanar reconstruction/maximum intensity projection/3D rendering
      can increase diagnostic sensitivity.

PMID- 22992605
TI  - Liver MRI at 3.0 tesla: comparison of image quality and lesion detectability
      between single-source conventional and dual-source parallel radiofrequency
      transmissions.
AB  - OBJECTIVE: To prospectively and intraindividually compare liver magnetic
      resonance imaging (MRI) using single-source and dual-source parallel
      radiofrequency (RF) transmissions at 3.0-T for image quality, lesion
      detectability, and lesion contrast. METHODS: Ninety-nine patients with 139 liver
      lesions underwent liver MRI at 3.0-T. Two radiologists performed a consensus
      review of T2-weighted images (T2WI), heavily T2WI (HT2WI), gadoxetic acid
      enhanced hepatobiliary images, and diffusion-weighted imaging using single-source
      and dual-source RF transmissions with regard to image quality and lesion
      detectability. Contrast ratios between liver lesions and liver parenchyma were
      also calculated. RESULTS: Image quality was better with dual-source than with
      single-source at T2WI and HT2WI (P < 0.05), but lesion detectabilities were
      similar for all sequences. There was no significant difference in mean contrast
      ratios for all sequences (P > 0.05). CONCLUSION: Dual-source RF transmission
      provides a better image quality with T2WI and HT2WI than with single-source.
      However, 2 techniques showed similar lesion detectability.

PMID- 22992607
TI  - Validation of dual-source single-tube reconstruction as a method to obtain half
      dose images to evaluate radiation dose and noise reduction: phantom and human
      assessment using CT colonography and sinogram-affirmed iterative reconstruction
      (SAFIRE).
AB  - OBJECTIVE: To evaluate a method for obtaining half-dose CT images for observer
      studies evaluating lower-dose CT. METHODS: Phantoms of varying sizes were scanned
      at multiple tube potentials using dose-matched dual-source (DS) and single-source
      (SS) protocols. Images from single-tube reconstruction of DS data were compared
      with SS images acquired at half-original CTDIvol. Thirty patients underwent
      supine SS and dose-matched prone DS CT colonography (CTC). Half-dose prone images
      were reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE). Two
      radiologists scored image quality on 2-dimensional (2D) and 3D images. RESULTS:
      Image noise was similar between half-dose SS images and DS images reconstructed
      from one tube only with tube potential of 120 kV or more for phantoms 40 cm or
      smaller (P < 0.05). For both readers, the patients' CTC image quality scores were
      more than 84% concordant between SS or DS CTC images, and half-dose-prone CTC
      images with SAFIRE had 84% or more concordance with routine-dose CTC except for
      3D image noise. CONCLUSIONS: In appropriately sized patients, DS acquisition with
      single-tube reconstruction can create half-dose images, permitting comparison to
      full-dose images. For CTC, there is comparable image quality for colonic
      evaluation between full-dose and half-dose images reconstructed with SAFIRE.

PMID- 22992606
TI  - Toward biphasic computed tomography (CT) enteric contrast: material
      classification of luminal bismuth and mural iodine in a small-bowel phantom using
      dual-energy CT.
AB  - OBJECTIVE: To develop dual-energy computed tomography methods for identification
      of hyperenhancing, hypoenhancing, and nonenhancing small-bowel pathologies.
      METHODS: Small-bowel phantoms simulating varying patient sizes and polyp types
      (hyperenhancing, hypoenhancing, and nonenhancing) contained bismuth suspension in
      the lumen. Dual-energy CT was performed at 80/140 kV and 100/140 kV. Computed
      tomographic number ratios (CT numbers at low/high kilovoltage) were calculated.
      Two radiologists evaluated polyp detection and conspicuity using bismuth-only,
      iodine-only, iodine-overlay, and mixed-kilovoltage displays. RESULTS: Computed
      tomographic ratios for bismuth and iodine did not overlap. For hyperenhancing and
      nonenhancing polyps at 80/140 kV, iodine-overlay display yielded higher detection
      rate (96%, 94%) and conspicuity score (3.5, 3.1) than mixed-kilovoltage images
      (88%, 68%; 1.5, 2.7). Mixed-kV images performed slightly better for hypoenhancing
      polyps (92%, 3.4 vs. <80%, <2.9). Similar results were observed at 100/140kV.
      CONCLUSIONS: Dual-energy CT and a bismuth-containing enteric contrast permitted
      simultaneous identification of hyperenhancing, hypoenhancing, and nonenhancing
      polyps over a range of patient sizes.

PMID- 22992608
TI  - Clinical and radiologic features of fungal diseases of the paranasal sinuses.
AB  - OBJECTIVE: To document the clinical and imaging characteristics of fungal
      rhinosinusitis (FRS). METHODS: Imaging studies of 28 patients with FRS were
      retrospectively analyzed, considering the type of fungal disease, location,
      signal characteristics, bone changes, expansion, and extrasinus extension.
      RESULTS: Acute invasive FRS showed unilateral pacifications of the sinonasal
      cavity, perisinus fat infiltration and/or bone destruction. Chronic invasive FRS
      demonstrated masslike hyperattenuating soft tissue, with bony destruction. The
      soft tissue changes were hypointense on T1 and markedly hypointense on T2
      weighted images. In allergic FRS, hyperattenuating soft tissue causing paranasal
      expansion due to allergic mucin was observed on CT. Fungus ball presented as a
      hyperattenuating lesion with calcifications within a single sinus. CONCLUSION:
      The radiological features of each type of FRS are distinctive and should afford a
      specific diagnosis in the proper clinical setting.

PMID- 22992609
TI  - Diffusion tensor imaging provides an insight into the microstructure of
      meningiomas, high-grade gliomas, and peritumoral edema.
AB  - OBJECTIVE: Fractional anisotropy (FA) is a measure for the degree of
      microstructural organization. Several studies have used FA values to assess
      microstructural organization of brain tumors and peritumoral edema. The purpose
      of our study was to validate FA and apparent diffusion constant (ADC) values in
      the diagnosis of meningiomas versus high-grade glial tumors, with the focus on
      the ability of diffusion tensor imaging (DTI) to reveal tumor ultrastructure. Our
      hypothesis was that FA and ADC values significantly differ between high-grade
      gliomas and meningiomas, and in the peritumoral edema. METHODS: Diffusion tensor
      imaging values were obtained from 20 patients with meningiomas (21 tumors) and 15
      patients with high-grade gliomas. Regions of interest were outlined in FA and ADC
      maps for solid-enhancing tumor tissue and peritumoral edema. Fractional
      anisotropy and ADC values were normalized by comparison to normal-appearing white
      matter (NAWM) in the contralateral hemisphere. Differences between meningiomas
      and high-grade gliomas were statistically analyzed. RESULTS: Meningiomas showed a
      significantly higher FA tumor/FA NAWM ratio (P = 0.0001) and lower ADC tumor/ADC
      NAWM ratio (P = 0.0008) compared to high-grade gliomas. On average, meningiomas
      also showed higher FA values in peritumoral edema than high-grade gliomas (P =
      0.016). Apparent diffusion constant values of peritumoral edema for the 2 tumor
      groups did not differ significantly (P = 0.5). CONCLUSIONS: Diffusion tensor
      imaging can be used to reveal microstructural differences between meningiomas and
      high-grade gliomas and may contribute toward predicting the histopathology of
      intracranial tumors. We advocate that diffusion tensor imaging should be included
      in the standard imaging protocol for patients with intracranial tumors.

PMID- 22992610
TI  - Computed tomographic venography for varicose veins of the lower extremities:
      prospective comparison of 80-kVp and conventional 120-kVp protocols.
AB  - OBJECTIVE: To prospectively investigate the feasibility of an 80-kilovolt (peak)
      (kVp) protocol in computed tomographic venography for varicose veins of the lower
      extremities by comparison with conventional 120-kVp protocol. METHODS:
      Attenuation values and signal-to-noise ratio of iodine contrast medium (CM) were
      determined in a water phantom for 2 tube voltages (80 kVp and 120 kVp). Among 100
      patients, 50 patients were scanned with 120 kVp and 150 effective milliampere
      second (mAs(eff)), and the other 50 patients were scanned with 80 kVp and 390
      mAs(eff) after the administration of 1.7-mL/kg CM (370 mg of iodine per
      milliliter). The 2 groups were compared for venous attenuation, contrast-to-noise
      ratio, and subjective degree of venous enhancement, image noise, and overall
      diagnostic image quality. RESULTS: In the phantom, the attenuation value and
      signal-to-noise ratio value for iodine CM at 80 kVp were 63.8% and 33.0% higher,
      respectively, than those obtained at 120 kVp. The mean attenuation of the
      measured veins of the lower extremities was 148.3 Hounsfield units (HU) for the
      80-kVp protocol and 94.8 HU for the 120-kVp protocol. Contrast-to-noise ratio was
      also significantly higher with the 80-kVp protocol. The overall diagnostic image
      quality of the 3-dimensional volume-rendered images was good with both protocols.
      The subjective score for venous enhancement was higher at the 80-kVp protocol.
      The mean volume computed tomography dose index of the 80-kVp (5.6 mGy) protocol
      was 23.3% lower than that of the 120-kVp (7.3 mGy) protocol. CONCLUSION: The use
      of the 80-kVp protocol improved overall venous attenuation, especially in
      perforating vein, and provided similarly high diagnostic image quality with a
      lower radiation dose when compared to the conventional 120-kVp protocol.

PMID- 22992611
TI  - Peripheral vessel scout imaging based on continuously moving table acquisition of
      projection data.
AB  - A fast and spatially seamless peripheral vessel scout is desirable for subsequent
      planning of magnetic resonance (MR) angiography. We implemented a continuously
      moving table sequence providing projection data with time-of-flight contrast of
      the entire lower extremities in less than 2 minutes. Variation of arterial signal
      during the cardiac cycle and autocorrelation were exploited to enhance vessel-to
      background contrast. Subjective image analysis revealed excellent vessel
      depiction, indicating that the proposed scout allows for seamless expedited
      visualization of major arterial structures.

PMID- 22992612
TI  - Adaptive statistical iterative reconstruction and Veo: assessment of image
      quality and diagnostic performance in CT colonography at various radiation doses.
AB  - OBJECTIVES: To evaluate the diagnostic performance of computed tomography (CT)
      colonography (CTC) reconstructed with different levels of adaptive statistical
      iterative reconstruction (ASiR, GE Healthcare) and Veo (model-based iterative
      reconstruction, GE Healthcare) at various tube currents in detection of polyps in
      porcine colon phantoms. METHODS: Five porcine colon phantoms with 46 simulated
      polyps were scanned at different radiation doses (10, 30, and 50 mA s) and were
      reconstructed using filtered back projection (FBP), ASiR (20%, 40%, and 60%) and
      Veo. Eleven data sets for each phantom (10-mA s FBP, 10-mA s 20% ASiR, 10-mA s
      40% ASiR, 10-mA s 60% ASiR, 10-mA s Veo, 30-mA s FBP, 30-mA s 20% ASiR, 30-mA s
      40% ASiR, 30-mA s 60% ASiR, 30-mA s Veo, and 50-mA s FBP) yielded a total of 55
      data sets. Polyp detection sensitivity and confidence level of 2 independent
      observers were evaluated with the McNemar test, the Fisher exact test, and
      receiver operating characteristic curve analysis. Comparative analyses of overall
      image quality score, measured image noise, and interpretation time were also
      performed. RESULTS: Per-polyp detection sensitivities and specificities were
      highest in 10-mA s Veo, 30-mA s FBP, 30-mA s 60% ASiR, and 50-mA s FBP
      (sensitivity, 100%; specificity, 100%). The area-under-the-curve values for the
      overall performance of each data set was also highest (1.000) at 50-mA s FBP, 30
      mA s FBP, 30-mA s 60% ASiR, and 10-mA s Veo. Images reconstructed with ASiR
      showed statistically significant improvement in per-polyp detection sensitivity
      as the percent level of per-polyp sensitivity increased (10-mA s FBP vs 10-mA s
      20% ASiR, P = 0.011; 10-mA s FBP vs 10-mA s 40% ASiR, P = 0.000; 10-mA s FBP vs
      10-mA s 60% ASiR, P = 0.000; 10-mA s 20% ASiR vs 40% ASiR, P = 0.034). Overall
      image quality score was highest at 30-mA s Veo and 50-mA s FBP. The quantitative
      measurement of the image noise was lowest at 30-mA s Veo and second lowest at 10
      mA s Veo. There was a trend of decrease in time required for image interpretation
      as the percent level of ASiR increased, and ASiR or Veo was used instead of FBP.
      However, differences from comparative analyses of overall image quality score,
      measured image noise, and interpretation time did not reach statistical
      significance. CONCLUSION: ASiR and Veo showed improved diagnostic performance
      with excellent sensitivity and specificity with less image noise and good image
      quality compared with FBP reconstruction of same radiation dose. Our study
      confirmed feasibility of low-dose CTC with iterative reconstruction as a
      promising screening tool with excellent diagnostic performance similar to that of
      the standard-dose CTC with FBP.

PMID- 22992613
TI  - Kilovoltage dependence of the attenuation of a potassium iodide/water solution on
      CT: presentation of a computer model implementing polychromatic character of the
      X-ray photon beam.
AB  - PURPOSE: To describe a program that simulates a computed tomographic scan with
      the polychromatic aspect of the output of the x-ray tube implemented. This
      program can be used in the study of the attenuation of different
      solutions/solutes. These results can subsequently guide the radiologist to obtain
      a satisfying contrast enhancement at lower tube voltages and eventually lower
      contrast volumes. MATERIALS AND METHODS: A Matlab program was written to simulate
      a computed tomographic scan. The spectrum of the x-ray tube at different
      kilovoltages was generated with another program (XOP) and used as input. Beam
      hardening correction and zero padding were added. The results were validated with
      attenuation measurements of a corresponding potassium iodide solution in water.
      RESULTS: There was a good agreement between the calculated and measured
      attenuations; the calculated results matched with the measured values and fell
      within a 5% deviation. CONCLUSION: It is possible to simulate correctly the
      attenuation of a potassium iodide in water solution in silico. This can be
      helpful to determine kilovoltages, administered contrast medium volumes and
      concentrations to reduce the irradiation of the patients, and obtain equally good
      contrast enhancement on a basis other than empirical.

PMID- 22992614
TI  - Image quality improvement using an image-based noise reduction algorithm: 
      initial experience in a phantom model for urinary stones.
AB  - OBJECTIVE: To determine signal-to-noise (SNR), contrast-to-noise ratio, and
      segmentation error measurements in various low-dose computed tomographic (CT)
      acquisitions of an anthropomorphic phantom containing urinary stones before and
      after implementation of a structure-preserving diffusion (SPD) denoising
      algorithm, and to compare the measurements with those of standard-dose CT
      acquisitions. METHODS: After institutional review board approval, written
      informed consent was waived and 36 calcium oxalate stones were evaluated after CT
      acquisitions in an anthropomorphic phantom at variable tube currents (33-137 mA
      s). The SPD denoising algorithm was applied to all images. Signal-to-noise ratio,
      contrast-to-noise ratio, and expected segmentation error were determined using
      manually drawn regions of interest to quantify the effect of the noise reduction
      on the image quality. RESULTS: The value of segmentation error measurements using
      the SPD denoising algorithm obtained at tube currents as low as 33 mA s (up to
      75% dose reduction level) were similar to standard imaging at 137 mA s. The
      denoised images at reduced doses up to 75% dose reduction have higher SNR than
      the standard-dose images without denoising (P < 0.005). Stepwise regression
      showed significant (P < 0.001) effect of dose length product on SNR, and
      segmentation error measurements. CONCLUSIONS: Based on objective noise-related
      image quality metrics, the SPD denoising algorithm may be useful as a robust and
      fast tool, and it has the potential to improve image quality in low-dose CT
      ureter protocols.

PMID- 22992615
TI  - Computed tomography (CT) bone segmentation of an ancient Egyptian mummy: a
      comparison of automated and semiautomated threshold and dual-energy techniques.
AB  - Dual-energy computed tomography (CT) enables 3-dimensional,noninvasive, and
      nondestructive imaging with material separation. Dual-energy CT is generally used
      to segment hydrated tissues within the clinical context. We apply dual-energy CT
      to an ancient Egyptian mummy and present several techniques designed to separate
      bone from desiccated tissue and resin. Automated and semiautomated dual-energy CT
      techniques are compared to manual segmentation and thresholding-based techniques.
      Semiautomated techniques enable substantial reductions in operator time compared
      to manual segmentation.

PMID- 22992616
TI  - Reproducibility of trabecular bone structure measurements of the distal radius at
      1.5 and 3.0 T magnetic resonance imaging.
AB  - The purpose of this study was to assess and compare the reproducibility of
      trabecular bone structure measurements of the distal radius at 1.5 and 3.0 T
      magnetic resonance imaging (MRI). Root mean square reproducibility errors ranged
      from 0.69% to 4.94% at 1.5 T MRI and from 0.38% to 5.80% at 3.0 T MRI. Thus,
      reproducibility errors of trabecular bone structure measurements are overall in
      an acceptable range and similar at 1.5 and 3.0 T MRI.

PMID- 22992618
TI  - Cyclosporin A inhibits colon cancer cell growth independently of the calcineurin
      pathway.
AB  - Chronic inflammation is a risk factor for the development of colon cancer,
      providing genotoxic insults, growth and pro-angiogenic factors that can promote
      tumorigenesis and tumor growth. Immunomodulatory agents can interfere with the
      inflammation that feeds cancer, but their impact on the transformed cell is
      poorly understood. The calcium/calcineurin signaling pathway, through activation
      of NFAT, is essential for effective immune responses, and its inhibitors
      cyclosporin A (CsA) and FK506 are used in the clinics to suppress immunity.
      Moreover, the kinases GSK3beta and mTOR, modulated by PI-3K/Akt, can inhibit NFAT
      activity, suggesting a cross-talk between the calcium and growth factor signaling
      pathways. Both NFAT and mTOR activity have been associated with tumorigenesis. We
      therefore investigated the impact of calcineurin and PI-3K/mTOR inhibition in
      growth of human colon carcinoma cells. We show that despite the efficient
      inhibition of NFAT1 activity, FK506 promotes tumor growth, whereas CsA inhibits
      it due to a delay in cell cycle progression and induction of necroptosis. We
      found NFkappaB activation and mTORC1 activity not to be altered by CsA or FK506.
      Similarly, changes to mitochondrial homeostasis were equivalent upon treatment
      with these drugs. We further show that, in our model, NFAT1 activation is not
      modulated by PI3K/mTOR. We conclude that CsA slows cell cycle progression and
      induces necroptosis of human carcinoma cell lines in a TGFbeta-, NFAT-, NFkappaB-
      and PI3K/mTOR-independent fashion. Nevertheless, our data suggest that CsA, in
      addition to its anti-inflammatory capacity, may target transformed colon and
      esophagus carcinoma cells without affecting non-transformed cells, promoting
      beneficial tumoristatic effects.

PMID- 22992621
TI  - Trimodality management of sinonasal undifferentiated carcinoma and review of the
      literature.
AB  - OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive
      malignancy with optimal management remains unclear. We performed a review of the
      impact of trimodality approach on SNUC outcome. METHODS: This is a single
      institution retrospective study of 18 patients, who were managed between 1997 and
      2009. The median age at presentation was 52 years (28 to 82). Nine patients (50%)
      were female. Three patients had stage II disease and underwent surgery alone, 12
      had stages III and IVa and underwent surgery combined with chemoradiation, and 3
      had stage IVb and underwent definitive chemoradiation. Patients who underwent
      preoperative, postoperative, and definitive chemoradiation received 60, 66, and
      70 Gy of radiation, respectively. In all patients receiving concurrent
      chemoradiation, cisplatin was used, at a dose of 100 mg/m every 3 weeks for 3
      cycles. Neoadjuvant chemotherapy included docetaxel, cisplatin, and 5
      fluorouracil (TPF) every 3 weeks for 2 to 3 cycles. RESULTS: After a median
      follow-up of 26 months (16 to 120), a total of 8 patients (44%) have experienced
      the following: 1 persistent disease (5.5%), 4 local failure (22%), and 3 distant
      metastases (DM, 16.5%). Five of the 8 patients had preexisting cranial nerve
      deficits or gross cranial invasion. The 2-, 3-, and 4-year local control (LC),
      disease-free survival (DFS), and overall survival (OS) were 78%, 72%, and 56%;
      75%, 65%, and 52%; and 75%, 50%, and 48%, respectively. Trimodality approach
      provided 83% LC and 92% DM-free survival, whereas other modalities provided 50%
      LC and 33% DM-free survival. The causes of death for the entire cohort were DM
      and local invasion. Acute chemoradiotherapy toxicity was 100% grades 1 and 2
      dermatitis, mucositis, and fatigue, 55% developed grades 1 and 2 dysphagia, and
      6% had grade 3 mucositis. Long-term toxicity was 28% grade 1 xerostomia, 11%
      retinopathy and optic neuropathy, and 6% orbital exenteration and grade 3
      peripheral neuropathy. CONCLUSIONS: SNUC is an aggressive neoplasm that
      frequently presents at an advanced stage. Our data show that trimodality approach
      in the form of surgery combined with chemoradiation seems to offer better LC and
      lower DM compared with other modalities.

PMID- 22992622
TI  - Radical hysterectomy compared with primary radiation for treatment of stage IB1
      cervix cancer.
AB  - OBJECTIVE: We reviewed data on treatment of stage IB1 cervical cancer at our
      institution to compare recurrence, complications, and survival of women treated
      primarily by radical hysterectomy versus radiation. METHODS: Records for women
      treated for stage IB1 cervical cancer between January 1, 1990 and June 1, 2010
      were retrospectively reviewed. Recurrence, survival outcomes, and complications
      were examined and compared. Demographic, clinical, and histopathologic factors
      were also analyzed. RESULTS: Of 198 patients with stage IB1 cervix cancer, 169
      (85%) underwent radical hysterectomy, including 37 (20%) who received
      postoperative radiation, and 29 (15%) were treated primarily with radiotherapy+/
      chemotherapy. Progression-free survival, overall survival, and disease-specific
      survival were all longer in the surgery group (89%, 95%, and 96%) versus the
      radiation group (70%, 70%, and 78%), respectively (P<0.001). Patients in the
      radiation group were older, had larger tumors, and were more likely to have
      medical comorbidities than patients in the surgery group. Within the surgical
      cohort, lymphvascular space invasion, outer third cervical stromal invasion,
      positive surgical margins, and lymph node metastasis were all predictive of
      recurrence (P<0.002), whereas histopathology, smoking, diabetes, and
      immunosuppression were not. Grade 3 or 4 complication rates were higher among the
      29 patients who had primary radiotherapy (20.7%) and the 37 patients who had
      surgery followed by radiotherapy (21.6%) compared with the 132 patients who had
      surgery only (9.1%) (P=0.047). CONCLUSIONS: Primary treatment of stage IB1 cervix
      cancer with radical hysterectomy+/-adjuvant radiation resulted in a significantly
      lower rate of recurrence and an improved survival with fewer complications
      compared with radiotherapy with or without chemotherapy.

PMID- 22992620
TI  - Epithelial-to-mesenchymal transition (EMT) confers primary resistance to
      trastuzumab (Herceptin).
AB  - The rate of inherent resistance to single-agent trastuzumab in HER2
      overexpressing metastatic breast carcinomas is impressive at above 70%.
      Unfortunately, little is known regarding the distinctive genetic signatures that
      could predict trastuzumab refractoriness ab initio. The epithelial-to-mesenchymal
      transition (EMT) molecular features, HER2 expression status and primary responses
      to trastuzumab were explored in the public Lawrence Berkeley Laboratory (LBL)
      Breast Cancer Collection. Lentivirus-delivered small hairpin RNAs were employed
      to reduce specifically and stably the expression of EMT transcription factors in
      trastuzumab-refractory basal/HER2+ cells. Cell proliferation assays and pre
      clinical nude mice xenograft-based studies were performed to assess the
      contribution of specific EMT transcription factors to inherent trastuzumab
      resistance. Primary sensitivity to trastuzumab was restricted to the SLUG/SNAIL2
      negative subset of luminal/HER2+ cell lines, whereas all of the SLUG/SNAIL2
      positive basal/HER2+ cell lines exhibited an inherent resistance to trastuzumab.
      The specific knockdown of SLUG/SNAIL2 suppressed the stem-related CD44+CD24(
      /low) mesenchymal immunophenotype by transcriptionally upregulating the luminal
      epithelial marker CD24 in basal/HER2+ cells. Basal/HER2+ cells gained sensitivity
      to the growth-inhibitory effects of trastuzumab following SLUG/SNAIL2 gene
      depletion, which induced the expression of the mesenchymal-to-epithelial
      transition (MET) genes involved in promoting an epithelial phenotype. The
      isolation of CD44+CD24(-/low) mesenchymal cells by magnetic-activated cell
      sorting (MACS) confirmed their intrinsic unresponsiveness to trastuzumab. A
      reduction in tumor growth and dramatic gain in sensitivity to trastuzumab in vivo
      were confirmed when the SLUG/SNAIL2 knockdown basal/HER2+ cells were injected
      into nude mice. HER2 overexpression in a basal, rather than in a luminal
      molecular background, results in a basal/HER2+ breast cancer subtype that is
      intrinsically resistant to trastuzumab. EMT transcription factors might induce an
      enhanced phenotypic plasticity that would allow basal/HER2+ breast cancer cells
      to "enter" into and "exit" dynamically from trastuzumab-responsive stem cell-like
      states. The systematic determination of SLUG/SNAIL2 as a stem/CD44+CD24(-/low)
      cell-associated protein may improve the therapeutic management of HER2+ breast
      carcinomas.

PMID- 22992623
TI  - Outcomes after involved-field radiation therapy (IFRT) with or without rituximab
      in patients with early-stage low-grade non-Hodgkin lymphoma (NHL) staged with CT
      and PET.
AB  - OBJECTIVES: We evaluated whether staging with positron emission tomography (PET)
      or treatment with rituximab after involved-field radiation therapy (IFRT) results
      in an improved progression-free survival (PFS) for early-stage indolent non
      Hodgkin lymphoma (NHL). METHODS: We identified 42 patients with stage I/II low
      grade NHL treated with initial IFRT at our institution between 1992 and 2009, who
      had been staged with computed tomography (CT) or PET. A retrospective analysis
      was performed to evaluate PFS according to staging by CT or PET, and by receipt
      of rituximab after IFRT. RESULTS: Overall PFS was 68% and 61% at 5 and 10 years,
      respectively. There was no significant difference in PFS whether patients were
      staged by CT (n=17) or by PET (n=25), with 5-year PFS rates of 76% and 60%,
      respectively. Eleven patients received 4 weekly doses of rituximab after IFRT,
      with no improvement in 5-year PFS: 46% for rituximab-treated patients versus 72%
      for patients who were not given rituximab. However, more patients who were given
      rituximab were stage II. CONCLUSIONS: Patients with limited stage indolent NHL
      staged with either CT or PET and treated with IFRT have favorable PFS compared
      with historical controls. The administration of 4 weekly doses of rituximab after
      IFRT did not improve PFS in these patients. The use of rituximab in this setting
      should be evaluated in a randomized prospective study.

PMID- 22992624
TI  - Factors associated with use of preoperative chemoradiation therapy for rectal
      cancer in the Cancer Care Outcomes Research and Surveillance Consortium.
AB  - PURPOSE: Preoperative (preop) chemoradiation therapy (CRT) improves local control
      and reduces toxicity more than postoperative (postop) CRT for the treatment of
      stages II/III rectal cancer, but studies suggest that many patients still receive
      postop CRT. We examined patient beliefs and clinical and provider characteristics
      associated with receipt of recommended therapy. METHODS: We identified stages
      II/III rectal cancer patients who had primary site resection and CRT among
      subjects in the Cancer Care Outcomes Research and Surveillance Consortium, a
      population-based and health system-based prospective cohort of newly diagnosed
      colorectal cancer patients from 2003 to 2005. Patient surveys and abstracted
      medical records were used to construct variables and determine sequence of CRT
      and surgery. Logistic regression was used to model the association between
      predictors and receipt of preop CRT. RESULTS: Of the 201 patients, 66% received
      preop and 34% received postop CRT. Those visiting a medical oncologist and/or
      radiation oncologist before a surgeon had a 96% (95% confidence interval, 92%
      100%) predicted probability of receiving preop CRT, compared with 48% (95%
      confidence interval, 41%-55%) for those visiting a surgeon first. Among those
      visiting a surgeon first, documentation of recommended staging procedures was
      associated with receiving preop CRT. CONCLUSIONS: Sequence of provider visits and
      documentation of recommended staging procedures were important predictors of
      receiving preop CRT. Initial multidisciplinary evaluation led to better adherence
      to CRT guidelines. Further evaluation of provider characteristics, referral
      patterns, and related health system processes should be undertaken to inform
      targeted interventions to reduce variation from recommended care.

PMID- 22992625
TI  - Clinical disparity and favorable prognoses for patients with Waldeyer ring
      extranodal nasal-type NK/T-cell lymphoma and diffuse large B-cell lymphoma.
AB  - OBJECTIVES: This study aimed to compare the clinical characteristics and
      prognosis of Waldeyer ring extranodal nasal-type natural killer (NK)/T-cell
      lymphoma (WR-NKTCL) and Waldeyer ring diffuse large B-cell lymphoma (WR-DLBCL).
      METHODS: Consecutive diagnoses of 122 WR-DLBCL and 44 WR-NKTCL patients,
      receiving mainly primary radiotherapy in early-stage WR-NKTCL and primary
      chemotherapy in early-stage WR-DLBCL, were reviewed. RESULTS: WR-NKTCL occurred
      predominately in young males, as nasopharyngeal stage I disease with B-symptoms,
      extranodal dissemination, and involving adjacent structures. WR-DLBCL was mainly
      stage II tonsillar disease with regional lymph node involvement. The 5-year
      overall survival (OS) and progression-free survival (PFS) rates were 74% and 67%
      in WR-DLBCL, respectively, and 68% (P=0.468) and 59% (P=0.303) in WR-NKTCL. In
      stages I and II disease, WR-DLBCL 5-year OS and PFS were 79% and 76% compared
      with 72% (P=0.273) and 62% (P=0.117) in WR-NKTCL. In stage I disease, WR-DLBCL 5
      year OS and PFS were 81% and 81%, compared with 76% (P=0.394) and 63% (P=0.236)
      in WR-NKTCL. In addition, the prognostic factors and failure patterns in WR-DLBCL
      and WR-NKTCL differed substantially. CONCLUSIONS: These results indicate that
      remarkable clinical disparities exist between WR-DLBCL and WR-NKTCL; however,
      different treatment strategies for each can result in similarly favorable
      prognoses.

PMID- 22992626
TI  - Linac-based stereotactic body radiotherapy for oligometastatic patients with
      single abdominal lymph node recurrent cancer.
AB  - OBJECTIVES: To evaluate stereotactic body radiotherapy (SBRT) for single
      abdominal lymph node cancer recurrence. METHODS: Inclusion criteria for this
      retrospective study were as follows: adult oligometastatic cancer patients with
      single abdominal lymph node recurrence that underwent SBRT but not other local
      therapy, written informed consent for treatment. Previous radiotherapy or
      concomitant systemic therapy were allowed. Toxicity and tumor response were
      evaluated using Radiation Therapy Oncology Group/European Organization for
      Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid
      Tumors. RESULTS: Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3
      fractions). Primary diagnosis included urological, gastrointestinal, gynecologic,
      and other malignancies. Concomitant systemic therapy was performed in 35 cases.
      Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity
      events were registered. Complete radiologic response, partial response,
      stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20
      (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response
      rates were similar when analysis was restricted to lesions treated with exclusive
      SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free
      interval, progression-free survival and overall-survival rates were 64.3%, 11.7%,
      and 49.9%, respectively. Overall-survival rates were significantly higher in
      favorable histology cases (prostate and kidney tumors). Pattern of failure was
      predominantly out-field. CONCLUSIONS: SBRT is a feasible approach for single
      abdominal lymph node recurrence, offering excellent in-field tumor control with
      low-toxicity profile. Future studies are warranted to identify the patients that
      benefit most from this treatment. The optimal combination with systemic treatment
      should also be defined.

PMID- 22992627
TI  - 3-Methyl-1,2-BN-cyclopentane: a promising H2 storage material?
AB  - We provide detailed characterization of properties for 3-methyl-1,2-BN
      cyclopentane 1 that are relevant to H(2) storage applications such as viscosity,
      thermal stability, H(2) gas stream purity, and polarity. The viscosity of 1 at
      room temperature is 25 +/- 5 cP, about one fourth the viscosity of olive oil.
      TGA/MS analysis indicates that liquid carrier 1 is thermally stable at 30 
      degrees C but decomposes slowly at 50  degrees C. RGA data suggest that the H(2)
      desorption from 1 is a clean process, producing relatively pure H(2) gas.
      Compound 1 is a polar zwitterionic-type liquid consistent with theoretical
      predictions and solvatochromic studies.

PMID- 22992628
TI  - Metalloproteins--a new challenge for metrology.

PMID- 22992629
TI  - Core-shell structured mesoporous silica as acid-base bifunctional catalyst with
      designated diffusion path for cascade reaction sequences.
AB  - A core-shell structured mesoporous silica nanosphere with antagonistic acid and
      basic sites spatially isolated and designated diffusion path was fabricated and
      served as an efficient acid-base bifunctional catalyst for one-pot cascade
      reaction sequences with excellent activity and selectivity.

PMID- 22992631
TI  - The meaning of being a primary nurse preceptor for newly graduated nurses.
AB  - Understanding the meaning of being the primary preceptor for newly graduated
      nurses during their transition into clinical practice has implications for
      hospital administrators, nurse leaders, and staff development nurses. This
      qualitative study explores the meaning of this experience through interviews with
      six preceptors. Findings suggest that nursing leaders need to clarify other roles
      that preceptors are expected to fill while precepting, implement a systematic
      approach to match preceptors with preceptees, and provide support for development
      of the preceptor role and daily preceptor practice.

PMID- 22992634
TI  - A group orientation model for new graduate nurses.
AB  - A local hospital implemented a unique, fiscally resourceful orientation strategy
      constructed by a nursing faculty professor designed to accommodate the needs of
      the graduate nurse (GN) in making the transition from academia to practice. The
      nurse faculty provided a reliable "hands-on" small group orientation to four new
      graduates simultaneously. This group orientation strategy provided these GNs with
      a preceptor, mentor, and role model to assist in their transition.

PMID- 22992633
TI  - Overcoming nursing faculty shortages and bridging the gap between education and
      practice.
AB  - The nurse faculty shortage and new requirements for teaching have led to
      thousands of qualified applicants being turned away from prelicensure nursing
      programs. In response, the Chief Nursing Officer in one organization created
      nursing faculty consultant positions to collaborate with faculty, teach
      prelicensure students in clinical practice, ensure the consistency of care by
      students in the hospital system, and enhance the relationships between schools of
      nursing and the organization. In the past 4 years the nursing faculty consultants
      have been employed they have taught over 500 nursing students from six different
      nursing programs.

PMID- 22992635
TI  - Nursing department education needs assessment: implementation and outcome.
AB  - The Education Council was interested in identifying learning needs. Previous
      needs assessments identified topics but did not assist in prioritizing education.
      A survey was developed with topics selected from quality and process initiatives.
      To prioritize education, a measurement scale based on Patricia Benner's skill
      development model was utilized, asking staff to rate their knowledge from novice
      to expert. Education programs have been prioritized by targeting topics with the
      highest novice responses. This assessment has also been utilized to measure the
      effectiveness of education. This is accomplished by having the staff rate their
      knowledge of topics the following year to evaluate learning.

PMID- 22992636
TI  - Designing a needs assessment survey for clinical nurse educators.
AB  - Clinical nurse educators frequently have a wide range of job responsibilities. In
      the changing healthcare environment, the identification of education needs must
      be specific, measurable, and applicable to their assigned responsibilities. A
      literature search into academic and industry professional development helped the
      authors develop a needs assessment survey for clinical nurse educators.

PMID- 22992637
TI  - Direct care nurses' knowledge in acute myocardial infarction treatment.
AB  - An acronym, a button, a script card, and a lot of fun are all an educator needs
      to turn dreaded education into a great learning experience for nurses as well as
      the patients. A multidisciplinary team pilot tested a new learning approach on a
      cardiac step-down unit. The goal was to educate both nurses and patients about
      the American Heart Association's Get-With-the-Guidelines Program for Coronary
      Artery Disease. The educational strategies were successful, and data revealed an
      increase in nursing knowledge of core measures. After a two-phase study, the
      program was eventually rolled out hospital-wide. The study results show that
      nurses' compliance with and knowledge of the AHA core measures increased as a
      direct result of the program.

PMID- 22992638
TI  - A mentoring model for evidence-based practice in a community hospital.
AB  - Significant emphasis has been placed on reducing barriers to implementing
      evidence-based practice and improving patient outcomes. The purpose of this study
      was to determine whether a mentor-led evidence-based practice quality improvement
      project would reduce professional nurses' perceptions of barriers to using best
      practice research findings in their practice to influence patient outcomes
      related to pressure ulcer prevalence.

PMID- 22992639
TI  - The midlife learner.
AB  - The author reviews the literature regarding midlife adult learners to determine
      the best educational methods to positively affect retention. Developing hospital
      based educational programs will meet the needs of the midlife learner and help
      retain nurses. Strategies reviewed include intergenerational mentoring, adapting
      to physiological age-related changes, linking new and prior learning, allowing
      time to acquire new skills, and deliberate planning for the future.

PMID- 22992640
TI  - The transition from student to new registered nurse in professional practice.
AB  - This qualitative study presents the transition experience of new registered
      nurses during the first year of professional practice. Four themes emerged:
      feelings of frustration and being overwhelmed, preceptors, fear, and the
      orientation process. The orientation process, quality, competent preceptors, and
      reducing lateral violence are key strategies to successfully retain new nurses.
      Nurse educators have a crucial role during nurse orientation, training
      preceptors, and reducing violent behaviors in the workplace.

PMID- 22992641
TI  - Nursing professional development:  stories, tips, and techniques.

PMID- 22992642
TI  - Storytelling...A tool for education, leadership, and team building.

PMID- 22992644
TI  - Engaging nurses in research utilization.
AB  - Research skills education is needed for nurses at all levels: novice,
      intermediate, and advanced. Nurse educators can help novice nurse researchers
      develop skills such as performing literature searches and critiquing research
      articles, which are necessary to develop and update clinical practice guidelines
      and implement evidence-based practice. The purpose of this article is to describe
      an innovative approach to encourage nurses to perform literature searches and
      critique research articles as a means to eventually engage in evidence-based
      practice.

PMID- 22992645
TI  - Neurogenetics: What makes a human brain?

PMID- 22992646
TI  - Receptors: Leaky receptors in stressed brains.

PMID- 22992648
TI  - Mesoporous vanadium nitride as a high performance catalyst support for formic
      acid electrooxidation.
AB  - Mesoporous vanadium nitride (VN) with high surface area and good electrical
      conductivity was prepared by a solid-solid phase separation method from a Zn
      containing vanadium oxide, Zn(3)V(2)O(8). The VN supported Pd catalyst exhibited
      significant catalytic activity for formic acid oxidation.

PMID- 22992647
TI  - Two cortical systems for memory-guided behaviour.
AB  - Although the perirhinal cortex (PRC), parahippocampal cortex (PHC) and
      retrosplenial cortex (RSC) have an essential role in memory, the precise
      functions of these areas are poorly understood. Here, we review the anatomical
      and functional characteristics of these areas based on studies in humans, monkeys
      and rats. Our Review suggests that the PRC and PHC-RSC are core components of two
      separate large-scale cortical networks that are dissociable by neuroanatomy,
      susceptibility to disease and function. These networks not only support different
      types of memory but also appear to support different aspects of cognition.

PMID- 22992650
TI  - Maya collapse cycles.

PMID- 22992649
TI  - NHERF1/EBP50 controls lactation by establishing basal membrane polarity complexes
      with prolactin receptor.
AB  - The development of the lactating mammary gland is a complex multifactorial
      process occurring in mammals during pregnancy. We show here that this process
      requires NHERF1/EBP50 (Na/H exchanger regulatory factor 1/ERM-binding
      phosphoprotein 50) expression and that successful lactation depends on NHERF1
      allele copy number, with rates of 50 and 20% in NHERF1(+/-) and (-/-) mice,
      respectively. The prolactin receptor (PRLR)-STAT5 signaling provides the central
      axis triggering the differentiation of secretory mammary alveolar cells. In
      successfully lactating glands, NHERF1 is massively upregulated and forms
      complexes with PRLR, but also with beta-catenin, E-cadherin and ezrin at the
      alveolar basal membrane, establishing basal polarity. In NHERF1-deficient glands,
      the basal polarity is disrupted, the PRLR levels and basal membrane localization
      are abolished, and the downstream STAT5 activation collapses with consequent
      reduction of milk protein synthesis. NHERF1/EBP50, a protein deregulated in
      breast cancer, thus emerges as an important physiological mediator of milk
      secretion, by engagement of PRLR in multimeric complexes at the alveolar basal
      membrane with subsequent network activation leading to cell differentiation.

PMID- 22992651
TI  - Cell-type specific deletion of GABA(A)alpha1 in corticotropin-releasing factor
      containing neurons enhances anxiety and disrupts fear extinction.
AB  - Corticotropin-releasing factor (CRF) is critical for the endocrine, autonomic,
      and behavioral responses to stressors, and it has been shown to modulate fear and
      anxiety. The CRF receptor is widely expressed across a variety of cell types,
      impeding progress toward understanding the contribution of specific CRF
      containing neurons to fear dysregulation. We used a unique CRF-Cre driver
      transgenic mouse line to remove floxed GABA(A)alpha1 subunits specifically from
      CRF neurons [CRF-GABA(A)alpha1 KO]. This process resulted in mice with decreased
      GABA(A)alpha1 expression only in CRF neurons and increased CRF mRNA within the
      amygdala, bed nucleus of the stria terminalis (BNST) and paraventricular nucleus
      of the hypothalamus. These mice show normal locomotor and pain responses and no
      difference in depressive-like behavior or Pavlovian fear conditioning. However,
      CRF-GABA(A)alpha1 KO increased anxiety-like behavior and impaired extinction of
      conditioned fear, coincident with an increase in plasma corticosterone
      concentration. These behavioral impairments were rescued with systemic or BNST
      infusion of the CRF antagonist R121919. Infusion of Zolpidem, a GABA(A)alpha1
      preferring benzodiazepine-site agonist, into the BNST of the CRF-GABA(A)alpha1 KO
      was ineffective at decreasing anxiety. Electrophysiological findings suggest a
      disruption in inhibitory current may play a role in these changes. These data
      indicate that disturbance of CRF containing GABA(A)alpha1 neurons causes
      increased anxiety and impaired fear extinction, both of which are symptoms
      diagnostic for anxiety disorders, such as posttraumatic stress disorder.

PMID- 22992652
TI  - Spontaneous shape reconfigurations in multicompartmental microcylinders.
AB  - Nature's particles, such as spores, viruses or cells, are adaptive--i.e., they
      can rapidly alter major phenomenological attributes such as shape, size, or
      curvature in response to environmental changes. Prominent examples include the
      hydration-mediated opening of ice plant seeds, actuation of pine cones, or the
      ingenious snapping mechanism of predatory Venus flytraps that rely on concave-to
      convex reconfigurations. In contrast, experimental realization of reconfigurable
      synthetic microparticles has been extremely challenging and only very few
      examples have been reported so far. Here, we demonstrate a generic approach
      towards dynamically reconfigurable microparticles that explores unique
      anisotropic particle architectures, rather than direct synthesis of sophisticated
      materials such as shape-memory polymers. Solely enabled by their architecture,
      multicompartmental microcylinders made of conventional polymers underwent active
      reconfiguration including shape-shifting, reversible switching, or three-way
      toggling. Once microcylinders with appropriate multicompartmental architectures
      were prepared by electrohydrodynamic cojetting, simple exposure to an external
      stimulus, such as ultrasound or an appropriate solvent, gives rise to interfacial
      stresses that ultimately cause reversible topographical reconfiguration. The
      broad versatility of the electrohydrodynamic cojetting process with respect to
      materials selection and processing suggests strategies for a wide range of
      dynamically reconfigurable adaptive materials including those with prospective
      applications for sensors, reprogrammable microactuators, or targeted drug
      delivery.

PMID- 22992653
TI  - Resolving a paradox of anomalous scalings in the diffusion of granular materials.
AB  - Granular materials do not perform Brownian motion, yet diffusion can be observed
      in such systems when agitation causes inelastic collisions between particles. It
      has been suggested that axial diffusion of granular matter in a rotating drum
      might be "anomalous" in the sense that the mean squared displacement of particles
      follows a power law in time with exponent less than unity. Further numerical and
      experimental studies have been unable to definitively confirm or disprove this
      observation. We show two possible resolutions to this apparent paradox without
      the need to appeal to anomalous diffusion. First, we consider the evolution of
      arbitrary (non-point-source) initial data towards the self-similar intermediate
      asymptotics of diffusion by deriving an analytical expression for the
      instantaneous collapse exponent of the macroscopic concentration profiles.
      Second, we account for the concentration-dependent diffusivity in bidisperse
      mixtures, and we give an asymptotic argument for the self-similar behavior of
      such a diffusion process, for which an exact self-similar analytical solution
      does not exist. The theoretical arguments are verified through numerical
      simulations of the governing partial differential equations, showing that
      concentration-dependent diffusivity leads to two intermediate asymptotic regimes:
      one with an anomalous scaling that matches the experimental observations for
      naturally polydisperse granular materials, and another with a "normal" diffusive
      scaling (consistent with a "normal" random walk) at even longer times.

PMID- 22992657
TI  - Parents' perceptions of their adolescent sons' recovery in a therapeutic
      community for addicted clients.
AB  - A qualitative phenomenological study of parents of addicted male adolescents who
      were residents of a Jewish therapeutic community (TC) describes and interprets
      the parents' perceptions of the recovery process. Deep, semistructured interviews
      with 14 parents provided the data. The parents' perceptions were clustered into
      three main themes of meaning: (a) the process of change, (b) the experiences of
      family members in the course of the son's recovery process, and (c) the parents'
      perception of the treatment at Retorno. According to the parents, the admission
      of their sons into the TC brought notable relief to the family life, which
      enabled the whole family to begin a recovery process. The findings support the
      positive criminology perspective that emphasizes the disintegration-integration
      vector as significant in the recovery process. Recommendations for intervention
      planning are provided. 

PMID- 22992658
TI  - Highly reproducible and sensitive surface-enhanced Raman scattering from
      colloidal plasmonic nanoparticle via stabilization of hot spots in graphene oxide
      liquid crystal.
AB  - Although it is now well recognized that plasmonic gold/silver nanoparticle based
      aggregates having electromagnetic hot spots are responsible for high sensitivity
      in surface-enhanced Raman spectroscopy (SERS), the high yield and reproducible
      production of such nanostructures are challenging and limit their practical
      application. Here we show a graphene oxide (GO) based approach in generating
      stable electromagnetic hot spots with high yield from colloidal plasmonic
      nanoparticles that leads to highly reproducible, stable and sensitive SERS for a
      wide range of molecules with Raman enhancement factors between 10(8) to 10(11).
      The liquid crystalline property of dispersed GO directs the Raman probe induced
      controlled aggregation of plasmonic particles, restricting those aggregates to
      small and discrete clusters and stabilizing those clusters for longer times
      offering the Raman probe induced 'turn on' SERS with high sensitivity and
      reproducibility. The presented approach is broadly applicable to different types
      of colloidal plasmonic particles and a wide range of Raman probes and is ideal
      for SERS based reliable detection of analyte at ultralow concentration.

PMID- 22992659
TI  - Pd-catalyzed borylative cyclisation of 1,7-enynes.
AB  - Reaction of a variety of 1,7-enynes with bis(pinacolato) diboron catalysed by Pd
      bis(trifluoroacetate) affords homoallylic and allylic boronates containing a six
      membered carbo- or heterocycle, by formation of C-C and C-B bonds.

PMID- 22992660
TI  - Ferrocenyl(trihydro)borates: building blocks for the synthesis of
      heterooligonuclear metallocene complexes.
AB  - The reaction of [Cp(2)ZrCl(2)] with the lithium salt Li[FcBH(3)] in
      stoichiometric ratios of 1.5 : 1 or 0.4 : 1 furnishes the mixed-metallocene
      complexes [Cp(2)(Cl)Zr(H(3)BFc)] (1) and [Cp(2)Zr(H(3)BFc)(2)] (3), respectively
      (Cp = cyclopentadienyl; Fc = ferrocenyl). When the two reagents are combined in a
      ratio of 0.6 : 1, complex 1 is formed together with the zirconium hydride species
      [Cp(2)(H)Zr(H(3)BFc)] (2). Compound 2 can be obtained in pure form from
      [Cp(2)Zr(H)Cl] and Li[FcBH(3)]. Treatment of the half-sandwich complexes
      [(C(5)R(5))ZrCl(3)] with 3 equivalents of Li[FcBH(3)] leads to the
      heterotetranuclear aggregates [(C(5)R(5))Zr(H(3)BFc)(3)] (4: R = H; 5: R =
      CH(3)). Li(2)[fc(BH(3))(2)] and 3 equivalents of [Cp(2)ZrCl(2)] give the
      heterotrinuclear compound [fc(BH(3)Zr(Cl)Cp(2))(2)] (6) with bridging
      ferrocenylene core (fc = 1,1'-ferrocenylene). According to X-ray crystallography,
      the trihydroborate ions are coordinated in a [Zr(MU-H)(2)B(H)-] fashion in 1, 2,
      3 and 6, whereas 4 and 5 are carrying tridentate trihydroborate ligands.

PMID- 22992661
TI  - Catalysis-based enantioselective total synthesis of myxothiazole Z, (14S)
      melithiazole G and (14S)-cystothiazole F.
AB  - A common strategy for the stereoselective and protecting group-free total
      synthesis of the myxobacterial antibiotics myxothiazole Z, (14S)-melithiazole G
      and (14S)-cystothiazole F is described featuring an asymmetric organocatalytic
      transfer hydrogenation, a palladium-catalyzed Stille coupling and a cross
      metathesis as the key steps.

PMID- 22992663
TI  - Achieving the promise of personalized medicine.
AB  - Individualized therapy is the practice of tailoring therapeutic intervention to a
      patient's disease, demographic characteristics, genetics, environment, lifestyle,
      and health status. In addition to previous methods of individualization,
      individualization based on pharmacogenomics is an emerging practice. Although
      tools are available to aid the determination of the need to individualize
      therapy, there are barriers to implementation. Various institutions have
      instituted programs to demonstrate the benefit of individualization, including
      programs that involve preemptive genotyping.

PMID- 22992666
TI  - Without an adequate ethical infrastructure, the road to personalized medicine
      will be rocky at best.
AB  - Discovering the genetic variations that create profiles of risk and drive
      individual responses to drugs and vaccines has proven more difficult than many
      initially presupposed. Rhetoric about the prospect of personalized medicine has
      exceeded the ability to deliver on that vision. There also remain significant
      ethical and policy obstacles that may hinder the arrival of personalized
      medicine. The emergence of new prenatal genetic tests make the resolution of
      these ethical challenges imperative.

PMID- 22992667
TI  - Ready when you are: easing into preemptive pharmacogenetics.
AB  - The promise of pharmacogenetics has included reduction of adverse drug events and
      enrichment for clinical efficacy. However, there has been very little assessment
      of the context in which this promise could be delivered. There are issues of
      return on effort and end points of meaningful impact that are crucial to moving
      this area of clinical pharmacology into practical benefit for our health system.

PMID- 22992668
TI  - Pharmacogenomics knowledge for personalized medicine.
AB  - The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects,
      curates, and disseminates information about the impact of human genetic variation
      on drug responses. It provides clinically relevant information, including dosing
      guidelines, annotated drug labels, and potentially actionable gene-drug
      associations and genotype-phenotype relationships. Curators assign levels of
      evidence to variant-drug associations using well-defined criteria based on
      careful literature review. Thus, PharmGKB is a useful source of high-quality
      information supporting personalized medicine-implementation projects.

PMID- 22992669
TI  - Individualized dosing with anesthetic agents.
AB  - The development of fundamental pharmacokinetics and pharmacodynamics concepts has
      enabled anesthesiologists to choose and dose anesthetic agents on a rational
      basis. The application of these concepts to a variety of clinical scenarios and
      patient populations makes it possible to individualize the dose, thereby
      decreasing the risk of complications. As more knowledge is gained about the
      sometimes profound differences in drug response, empirical dosing such as in
      milligrams per kilogram of total body weight is disappearing from the anesthesia
      specialty.

PMID- 22992670
TI  - In search of physiologically based distribution volume estimates for
      macromolecules.
AB  - In their semimechanistic analysis of trastuzumab emtansine (T-DM1)
      pharmacokinetics, Chudasama et al., as reported in this issue, modeled the
      process of T-DM1 deconjugation with a series of transit compartments representing
      plasma volume and a single peripheral compartment. The implausibility of the two
      compartment distribution model used in this study as well as in other recent
      attempts to analyze the distribution kinetics of trastuzumab and other
      macromolecules reflects the fact that this modeling has been guided primarily by
      statistical rather than physiological considerations.

PMID- 22992671
TI  - Aromaticity: a web themed issue.

PMID- 22992672
TI  - A hydrogen bond scaffold supported synthetic heme Fe(III)-O2(-) adduct.
AB  - A hydrogen bonded heme-Fe(III)-O(2)(-) adduct is stabilized and characterized
      using resonance Raman and EPR spectroscopy. The low O-O vibrations of this
      complex are quite different from those reported for other heme-Fe(III)-O(2)(-)
      adducts.

PMID- 22992673
TI  - Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal
      collecting duct cells.
AB  - Vasopressin regulates transport across the collecting duct epithelium in part via
      effects on gene transcription. Transcriptional regulation occurs partially via
      changes in phosphorylation of transcription factors, transcriptional
      coactivators, and protein kinases in the nucleus. To test whether vasopressin
      alters the nuclear phosphoproteome of vasopressin-sensitive cultured mouse mpkCCD
      cells, we used stable isotope labeling and mass spectrometry to quantify
      thousands of phosphorylation sites in nuclear extracts and nuclear pellet
      fractions. Measurements were made in the presence and absence of the vasopressin
      analog dDAVP. Of the 1,251 sites quantified, 39 changed significantly in response
      to dDAVP. Network analysis of the regulated proteins revealed two major clusters
      ("cell-cell adhesion" and "transcriptional regulation") that were connected to
      known elements of the vasopressin signaling pathway. The hub proteins for these
      two clusters were the transcriptional coactivator beta-catenin and the
      transcription factor c-Jun. Phosphorylation of beta-catenin at Ser552 was
      increased by dDAVP [log(2)(dDAVP/vehicle) = 1.79], and phosphorylation of c-Jun
      at Ser73 was decreased [log(2)(dDAVP/vehicle) = -0.53]. The beta-catenin site is
      known to be targeted by either protein kinase A or Akt, both of which are
      activated in response to vasopressin. The c-Jun site is a canonical target for
      the MAP kinase Jnk2, which is downregulated in response to vasopressin in the
      collecting duct. The data support the idea that vasopressin-mediated control of
      transcription in collecting duct cells involves selective changes in the nuclear
      phosphoproteome. All data are available to users at
      http://helixweb.nih.gov/ESBL/Database/mNPPD/.

PMID- 22992674
TI  - Mutations that reduce its specific DNA binding inhibit high NaCl-induced nuclear
      localization of the osmoprotective transcription factor NFAT5.
AB  - The transcription factor nuclear factor of activated T cell 5 (NFAT5) is
      activated by the stress of hypertonicity (e.g., high NaCl). Increased expression
      of NFAT5 target genes causes accumulation of protective organic osmolytes and
      heat shock proteins. Under normotonic conditions (~300 mosmol/kgH(2)O), NFAT5 is
      distributed between the nucleus and cytoplasm, hypertonicity causes it to
      translocate into the nucleus, and hypotonicity causes it to translocate into the
      cytoplasm. The mechanism of translocation is complex and not completely
      understood. NFAT5-T298 is a known contact site of NFAT5 with its specific DNA
      element [osmotic response element (ORE)]. In the present study, we find that
      mutation of NFAT5-T298 to alanine or aspartic acid not only reduces binding of
      NFAT5 to OREs (EMSA) but also proportionately reduces high NaCl-induced nuclear
      translocation of NFAT5. Combined mutation of other NFAT5 DNA contact sites
      (R293A/E299A/R302A) also greatly reduces both specific DNA binding and nuclear
      localization of NFAT5. NFAT5-T298 is a potential phosphorylation site, but, using
      protein mass spectrometry, we do not find phosphorylation at NFAT5-T298. Further,
      decreased high NaCl-induced nuclear localization of NFAT5 mutated at T298 does
      not involve previously known regulatory mechanisms, including hypotonicity
      induced export of NFAT5, regulated by phosphorylation of NFAT5-S155, XPO1
      (CRM1/exportin1)-mediated export of NFAT5 from the nucleus, or hypertonicity
      induced elevation of NUP88, which enhances nuclear localization of NFAT5. We
      conclude that specific DNA binding of NFAT5 contributes to its nuclear
      localization, by mechanisms, as yet undetermined, but independent of ones
      previously described to regulate NFAT5 distribution.

PMID- 22992676
TI  - Tribute to L. J. Henderson, a remarkable physiologist, and the founder of the
      American School of Sociology (1878-1942).

PMID- 22992675
TI  - Selective inhibition of phosphodiesterase 1 relaxes urinary bladder smooth
      muscle: role for ryanodine receptor-mediated BK channel activation.
AB  - The large conductance voltage- and Ca(2+)-activated K(+) (BK) channel is a major
      regulator of detrusor smooth muscle (DSM) excitability and contractility.
      Recently, we showed that nonselective phosphodiesterase (PDE) inhibition reduces
      guinea pig DSM excitability and contractility by increasing BK channel activity.
      Here, we investigated how DSM excitability and contractility changes upon
      selective inhibition of PDE type 1 (PDE1) and the underlying cellular mechanism
      involving ryanodine receptors (RyRs) and BK channels. PDE1 inhibition with 8
      methoxymethyl-3-isobutyl-1-methylxanthine (8MM-IBMX; 10 MUM) increased the cAMP
      levels in guinea pig DSM cells. Patch-clamp experiments on freshly isolated DSM
      cells showed that 8MM-IBMX increased transient BK currents and the spontaneous
      transient hyperpolarization (STH) frequency by ~2.5- and ~1.8-fold, respectively.
      8MM-IBMX hyperpolarized guinea pig and human DSM cell membrane potential and
      significantly decreased the intracellular Ca(2+) levels in guinea pig DSM cells.
      Blocking BK channels with 1 MUM paxilline or inhibiting RyRs with 30 MUM
      ryanodine abolished the STHs and the 8MM-IBMX inhibitory effects on the DSM cell
      membrane potential. Isometric DSM tension recordings showed that 8MM-IBMX
      significantly reduced the spontaneous phasic contraction amplitude, muscle force
      integral, duration, frequency, and tone of DSM isolated strips. The electrical
      field stimulation-induced DSM contraction amplitude, muscle force integral, and
      duration were also attenuated by 10 MUM 8MM-IBMX. Blocking BK channels with
      paxilline abolished the 8MM-IBMX effects on DSM contractions. Our data provide
      evidence that PDE1 inhibition relaxes DSM by raising cellular cAMP levels and
      subsequently stimulates RyRs, which leads to BK channel activation, membrane
      potential hyperpolarization, and decrease in intracellular Ca(2+) levels.

PMID- 22992678
TI  - Differential role of IK and BK potassium channels as mediators of intrinsic and
      extrinsic apoptotic cell death.
AB  - An important event during apoptosis is regulated cell condensation known as
      apoptotic volume decrease (AVD). Ion channels have emerged as essential
      regulators of this process mediating the release of K(+) and Cl(-), which
      together with osmotically obliged water, results in the condensation of cell
      volume. Using a Grade IV human glioblastoma cell line, we examined the
      contribution of calcium-activated K(+) channels (K(Ca) channels) to AVD after the
      addition of either staurosporine (Stsp) or TNF-alpha-related apoptosis-inducing
      ligand (TRAIL) to activate the intrinsic or extrinsic pathway of apoptosis,
      respectively. We show that AVD can be inhibited in both pathways by high
      extracellular K(+) or the removal of calcium. However, BAPTA-AM was only able to
      inhibit Stsp-initiated AVD, whereas TRAIL-induced AVD was unaffected. Specific
      K(Ca) channel inhibitors revealed that Stsp-induced AVD was dependent on K(+)
      efflux through intermediate-conductance calcium-activated potassium (IK)
      channels, while TRAIL-induced AVD was mediated by large-conductance calcium
      activated potassium (BK) channels. Fura-2 imaging demonstrated that Stsp induced
      a rapid and modest rise in calcium that was sustained over the course of AVD,
      while TRAIL produced no detectable rise in global intracellular calcium.
      Inhibition of IK channels with clotrimazole or 1-[(2-chlorophenyl)
      diphenylmethyl]-1H-pyrazole (TRAM-34) blocked downstream caspase-3 activation
      after Stsp addition, while paxilline, a specific BK channel inhibitor, had no
      effect. Treatment with ionomycin also induced an IK-dependent cell volume
      decrease. Together these results show that calcium is both necessary and
      sufficient to achieve volume decrease and that the two major pathways of
      apoptosis use unique calcium signaling to efflux K(+) through different K(Ca)
      channels.

PMID- 22992677
TI  - Chronic hypoxia and VEGF differentially modulate abundance and organization of
      myosin heavy chain isoforms in fetal and adult ovine arteries.
AB  - Chronic hypoxia increases vascular endothelial growth factor (VEGF) and thereby
      promotes angiogenesis. The present study explores the hypothesis that hypoxic
      increases in VEGF also remodel artery wall structure and contractility through
      phenotypic transformation of smooth muscle. Pregnant and nonpregnant ewes were
      maintained at sea level (normoxia) or 3,820 m (hypoxia) for the final 110 days of
      gestation. Common carotid arteries harvested from term fetal lambs and
      nonpregnant adults were denuded of endothelium and studied in vitro. Stretch
      dependent contractile stresses were 32 and 77% of normoxic values in hypoxic
      fetal and adult arteries. Hypoxic hypocontractility was coupled with increased
      abundance of nonmuscle myosin heavy chain (NM-MHC) in fetal (+37%) and adult
      (+119%) arteries. Conversely, hypoxia decreased smooth muscle MHC (SM-MHC)
      abundance by 40% in fetal arteries but increased it 123% in adult arteries.
      Hypoxia decreased colocalization of NM-MHC with smooth muscle alpha-actin (SM
      alphaA) in fetal arteries and decreased colocalization of SM-MHC with SM-alphaA
      in adult arteries. Organ culture with physiological concentrations (3 ng/ml) of
      VEGF-A(165) similarly depressed stretch-dependent stresses to 37 and 49% of
      control fetal and adult values. The VEGF receptor antagonist vatalanib ablated
      VEGF's effects in adult but not fetal arteries, suggesting age-dependent VEGF
      receptor signaling. VEGF replicated hypoxic decreases in colocalization of NM-MHC
      with SM-alphaA in fetal arteries and decreases in colocalization of SM-MHC with
      SM-alphaA in adult arteries. These results suggest that hypoxic increases in VEGF
      not only promote angiogenesis but may also help mediate hypoxic arterial
      remodeling through age-dependent changes in smooth muscle phenotype and
      contractility.

PMID- 22992679
TI  - Intoxicated Na(+) channels. Focus on "ethanol stimulates epithelial sodium
      channels by elevating reactive oxygen species".

PMID- 22992680
TI  - H2S, a gasotransmitter for oxygen sensing in carotid body. Focus on "Endogenous
      H2S is required for hypoxic sensing by carotid body glomus cells".

PMID- 22992681
TI  - A nanotectonics approach to produce hierarchically organized bioactive glass
      nanoparticles-based macrospheres.
AB  - Bioactive particles have been widely used in a series of biomedical applications
      due to their ability to promote bone-bonding and elicit favorable biological
      responses in therapies associated with the replacement and regeneration of
      mineralized tissues. In this work hierarchical architectures are prepared by an
      innovative methodology using SiO(2)-CaO sol-gel based nanoparticles. Inspired by
      colloidal crystals, spherical aggregates were formed on biomimetic
      superhydrophobic surfaces using bioactive glass nanoparticles (BG-NPs) able to
      promote bone regeneration. A highly ordered organization, a common feature of
      mineralized structures in Nature, was achieved at both nano- and microlevels,
      being the crystallization degree of the structures controlled by the evaporation
      rates taking place at room temperature (RT) or at 4  degrees C. The
      crystallization degree of the structures influenced the Ca/P ratio of the
      apatitic film formed at their surface, after 7 days of immersion in SBF. This
      allows the regulation of bioactive properties and the ability to release
      potential additives that could be also incorporated in such particles with a high
      efficiency. Such a versatile method to produce bioactive particles with
      controlled size and internal structure could open new possibilities in designing
      new spherical devices for orthopaedic applications, including tissue engineering.

PMID- 22992682
TI  - Increased maternal microchimerism after open fetal surgery.
AB  - Maternal-fetal cellular trafficking (MFCT) during pregnancy leads to the presence
      of maternal cells in the fetus and of fetal cells in the mother. Since this
      process may be altered in cases of pregnancy complications, we asked whether open
      fetal surgery leads to changes in microchimerism levels. We analyzed maternal and
      fetal microchimerism in fetuses who underwent open fetal surgery for repair of
      spina bifida and compared their levels to patients who had postnatal repair and
      to healthy controls. We found that maternal microchimerism levels were increased
      in patients who had open fetal surgery compared with controls. In contrast,
      patients who had fetal intervention at the time of delivery did not demonstrate
      increased microchimerism. These results suggest that open fetal surgery may alter
      trafficking. Given the importance of MFCT in maternal-fetal tolerance, we discuss
      potential implications for the field of preterm labor and transplantation
      tolerance.

PMID- 22992684
TI  - Total synthesis of noricumazole B establishes D-arabinose as glycan unit.
AB  - The total synthesis of noricumazole B, a secondary metabolite from myxobacteria,
      was achieved. It established the glycan moiety to be D-alpha-arabinoside.

PMID- 22992685
TI  - The nursing model of care: don't forget the patient perspective.

PMID- 22992686
TI  - Make an impact with transformational leadership and shared governance.

PMID- 22992687
TI  - Embracing safe patient handling.

PMID- 22992688
TI  - The time is now: developing a nurse manager residency program.

PMID- 22992690
TI  - Intensity index: quantifying workloads and balancing assignments.

PMID- 22992691
TI  - Nurses and body art: what's your perception?

PMID- 22992692
TI  - Forging a new culture: blending Magnet(r) principles with Just Culture.

PMID- 22992693
TI  - Moving on up.

PMID- 22992694
TI  - Selective switchable iron-catalyzed hydrosilylation of carboxylic acids.
AB  - Selective reduction of carboxylic acids either to aldehydes or alcohols is
      achieved using a one pot procedure based on iron-catalyzed hydrosilylations.
      Using phenylsilane and (COD)Fe(CO)(3) catalyst under UV-irradiation at rt,
      alcohols were obtained specifically in good yields, whereas aldehydes were
      selectively obtained using TMDS and (t-PBO)Fe(CO)(3) catalyst under thermal
      activation.

PMID- 22992695
TI  - Artificial light-harvesting antenna systems grafted on a carbohydrate platform.
AB  - An enantiopure alpha-D-glucopyranoside derivative has been used as a platform to
      prepare artificial antenna systems based on bodipy subunits. Efficient and
      ultrafast energy transfer (in the fs and ps time regimes) takes place in the
      multibodipy systems.

PMID- 22992696
TI  - Intact INI1 gene region with paradoxical loss of protein expression in AT/RT:
      implications for a possible novel mechanism associated with absence of INI1
      protein immunoreactivity.

PMID- 22992699
TI  - DNA mismatch repair deficiency in breast carcinoma: a pilot study of triple
      negative and non-triple-negative tumors.
AB  - Recent studies have suggested that breast cancer is part of the tumor spectrum in
      Lynch syndrome (LS). However, the frequency and significance of DNA mismatch
      repair (MMR) deficiency in breast carcinoma in general is unclear. Some triple
      negative breast carcinomas (TNBCs) have morphologic features similar to those
      described in LS-associated colorectal carcinomas; therefore, we hypothesized that
      TNBCs might be more likely to have MMR deficiency. In this study, we tested our
      hypothesis in a series of 226 TNBCs along with a control series of 90 non-triple
      negative tumors, utilizing DNA MMR protein immunohistochemistry followed by PCR
      microsatellite instability testing and MLH1 promoter methylation testing. By
      immunohistochemistry, we identified 4 triple-negative carcinomas (4/226, 1.8%)
      showing loss of MMR proteins (3 lost MLH1 and PMS2, and 1 lost MSH2 and MSH6);
      whereas none of the 90 non-triple-negative carcinomas showed loss of protein.
      Further testing of the 3 MLH1/PMS2 protein-deficient carcinomas identified 1
      tumor showing high-frequency microsatellite instability and MLH1 promoter
      hypermethylation. All 4 MMR protein-deficient carcinomas were ductal type with
      high histologic and nuclear grades. Prominent lymphocytic infiltration was noted
      in 2 tumors. The clinical characteristics and survival outcome varied widely
      among the 4 patients. In conclusion, our results suggest that DNA MMR deficiency
      is rare in breast carcinoma, and as such, testing of breast carcinoma for the
      detection of LS may best be restricted to high-risk individuals only. Our data
      also suggest that not all MMR protein-deficient breast tumors show microsatellite
      instability, and MLH1 promoter methylation is the molecular basis for at least a
      subset of microsatellite instable breast tumors. Although MMR-deficient breast
      carcinomas share certain morphologic features with the more typical types of LS
      associated tumors, better characterization, and a better understanding of their
      clinical behavior await further analysis with a larger sample size.

PMID- 22992698
TI  - Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57
      immunohistochemistry and molecular genotyping) improve morphologic diagnosis for
      both recently trained and experienced gynecologic pathologists.
AB  - Distinction of hydatidiform moles from nonmolar specimens (NMs) and
      subclassification of hydatidiform moles as complete hydatidiform mole (CHM) and
      partial hydatidiform mole (PHM) are important for clinical practice and
      investigational studies; however, diagnosis based solely on morphology is
      affected by interobserver variability. Molecular genotyping can distinguish these
      entities by discerning androgenetic diploidy, diandric triploidy, and biparental
      diploidy to diagnose CHMs, PHMs, and NMs, respectively. Eighty genotyped cases
      (27 CHMs, 27 PHMs, 26 NMs) were selected from a series of 200 potentially molar
      specimens previously diagnosed using p57 immunohistochemistry and genotyping.
      Cases were classified by 6 pathologists (3 faculty level gynecologic pathologists
      and 3 fellows) on the basis of morphology, masked to p57 immunostaining and
      genotyping results, into 1 of 3 categories (CHM, PHM, or NM) during 2 diagnostic
      rounds; a third round incorporating p57 immunostaining results was also
      conducted. Consensus diagnoses (those rendered by 2 of 3 pathologists in each
      group) were also determined. Performance of experienced gynecologic pathologists
      versus fellow pathologists was compared, using genotyping results as the gold
      standard. Correct classification of CHMs ranged from 59% to 100%; there were no
      statistically significant differences in performance of faculty versus fellows in
      any round (P-values of 0.13, 0.67, and 0.54 for rounds 1 to 3, respectively).
      Correct classification of PHMs ranged from 26% to 93%, with statistically
      significantly better performance of faculty versus fellows in each round (P
      values of 0.04, <0.01, and <0.01 for rounds 1 to 3, respectively). Correct
      classification of NMs ranged from 31% to 92%, with statistically significantly
      better performance of faculty only in round 2 (P-values of 1.0, <0.01, and 0.61
      for rounds 1 to 3, respectively). Correct classification of all cases combined
      ranged from 51% to 75% by morphology and 70% to 80% with p57, with statistically
      significantly better performance of faculty only in round 2 (P-values of 0.69,
      <0.01, and 0.15 for rounds 1 to 3, respectively). p57 immunostaining
      significantly improved recognition of CHMs (P<0.01) and had high reproducibility
      (kappa=0.93 to 0.96) but had no impact on distinction of PHMs and NMs. Genotyping
      provides a definitive diagnosis for the ~25% to 50% of cases that are
      misclassified by morphology, especially those that are also unresolved by p57
      immunostaining.

PMID- 22992700
TI  - Nickel-iron dithiolates related to the deactivated [NiFe]-hydrogenases.
AB  - Described herein are preparations of synthetic models for the deactivated
      Ni(II)Fe(II) states of the [NiFe]-hydrogenases. Iodination of the S = 1/2 species
      [(dppe)Ni(pdt)Fe(CO)(3)](+) afforded the diamagnetic iodo complex
      [(dppe)Ni(pdt)IFe(CO)(3)](+). Crystallographic analysis of this species confirmed
      the presence of square-pyramidal Ni linked to an octahedral Fe centre. The NiFe
      separation of 3.018 A indicated the absence of metal-metal bonding. This complex
      could be reduced to give (dppe)Ni(pdt)Fe(CO)(3) and, in the presence of iodide,
      decarbonylated to afford (dppe)Ni(pdt)FeI(2). Derivatives of the type
      [(diphosphine)Ni(dithiolate)XFe(CO)(2)L](+) (X = Cl, Br, I) were prepared by
      halogenation of mixed-valence precursors
      [(diphosphine)Ni(dithiolate)Fe(CO)(2)L](+) (diphosphine = dppe, dcpe; L =
      tertiary phosphine or CO). The Fe(CO)(2)(PR(3))-containing derivatives are more
      robust than the related tricarbonyl derivatives. Exploiting this greater
      stability, we characterised examples of chloride and bromide derivatives. Related
      fluorides could be prepared by F(-) abstraction from BF(4)(-). Spectroscopic
      evidence is presented for the hydroperoxide [(dppe)Ni(pdt)(OOH)Fe(CO)(2)L](+),
      which represents a model for the Ni-SU state.

PMID- 22992702
TI  - Analysis of the impact of intravenous LH pulses versus continuous LH infusion on
      testosterone secretion during GnRH-receptor blockade.
AB  - Gonadotrophin-releasing hormone (GnRH) pulsatility is required for optimal
      luteinizing hormone (LH) secretion, but whether LH pulsatility is required for
      physiological testosterone (T) secretion is not known. To test the postulate that
      pulses of recombinant human (rh) LH stimulate greater T secretion than continuous
      infusion of the same dose, a potent selective GnRH antagonist was administered
      overnight to 19 healthy men ages 18-49 yr. Subjects then received saline or rhLH
      intravenously continuously or as 6-min pulses intravenously every 1 or 2 h at the
      same total dose. Blood was sampled every 10 min for 10 h to quantify T responses.
      For the four interventions, the descending rank order of mean LH and mean T
      concentrations was 1-h = 2-h rhLH pulses > continuous rhLH > saline (P < 10(-3)).
      Plateau LH and T concentrations correlated positively (R(2) = 0.943, P = 0.029)
      as did LH concentrations and LH half-lives (R(2) = 0.962, P = 0.019). Percentage
      pulsatile T secretion assessed by deconvolution analysis (Keenan DM, Takahashi
      PY, Liu PY, Roebuck PD, Nehra AX, Iranmanesh A, Veldhuis JD. Endocrinology 147:
      2817-2828, 2006) was the highest (P = 0.019), and half-time to attain peak T
      concentrations was the shortest (P < 10(-6)), for 1-h rhLH pulses. Approximate
      entropy (a pattern-regularity measure) revealed more orderly T secretion for 1-
      than 2-h rhLH pulses (P = 0.0076). Accordingly, a pulsatile LH signal, while not
      obligatory to maintain mean T concentrations, controls the mean plasma LH
      concentration and determines quantifiable patterns of T secretion. These data
      introduce the question whether blood T patterns in turn supervise distinctive
      target-tissue responses.

PMID- 22992703
TI  - Telomeres, tethers and trypanosomes.
AB  - Temporal and spatial organization of the nucleus is critical for the control of
      transcription, mRNA processing and the assembly of ribosomes. This includes the
      occupancy of specific territories by mammalian chromosomes, the presence of
      subnuclear compartments such as the nucleolus and Cajal bodies and the division
      of chromatin between active and inactive states. These latter are commonly
      associated with the location of DNA within euchromatin and heterochromatin
      respectively; critically these distinctions arise through modifications to
      chromatin-associated proteins, including histones, as well as the preferential
      localization of heterochromatin at the nuclear periphery. Most research on
      nuclear organization has focused on metazoa and fungi; however, recent technical
      advances have made more divergent eukaryotes accessible to study, with some
      surprising results. For example, the organization of heterochromatin is mediated
      in metazoan nuclei in large part by lamins, the prototypical intermediate
      filament proteins. Despite the presence of heterochromatin, detected both
      biochemically and by EM in most eukaryotic organisms, until this year lamins were
      thought to be restricted to metazoan taxa, and the proteins comprising the lamina
      in other lineages were unknown. Recent work indicates the presence of lamin
      orthologs in amoeba, while trypanosomatids possess a large coiled-coil protein,
      NUP-1, that performs functions analogous to lamins. These data indicate that the
      presence of a nuclear lamina is substantially more widespread than previously
      thought, with major implications for the evolution of eukaryotic gene expression
      mechanisms. We discuss these and other recent findings on the organization of
      nuclei in diverse organisms, and the implications of these findings for the
      evolutionary origin of eukaryotes.

PMID- 22992704
TI  - Amplitude rise time does not cue the /ba/-/wa/ contrast for adults or children.
AB  - PURPOSE: Previous research has demonstrated that children weight the acoustic
      cues to many phonemic decisions differently than do adults and gradually shift
      those strategies as they gain language experience. However, that research has
      focused on spectral and duration cues rather than on amplitude cues. In the
      current study, the authors examined amplitude rise time (ART; an amplitude cue)
      and formant rise time (FRT; a spectral cue) in the /b/-/w/ manner contrast for
      adults and children, and related those speech decisions to outcomes of nonspeech
      discrimination tasks. METHOD: Twenty adults and 30 children (ages 4-5 years)
      labeled natural and synthetic speech stimuli manipulated to vary ARTs and FRTs,
      and discriminated nonspeech analogs that varied only by ART in an AX paradigm.
      RESULTS: Three primary results were obtained. First, listeners in both age groups
      based speech labeling judgments on FRT, not on ART. Second, the fundamental
      frequency of the natural speech samples did not influence labeling judgments.
      Third, discrimination performance for the nonspeech stimuli did not predict how
      listeners would perform with the speech stimuli. CONCLUSION: Even though both
      adults and children are sensitive to ART, it was not weighted in phonemic
      judgments by these typical listeners.

PMID- 22992705
TI  - Verb comprehension and use in children and adults with Down syndrome.
AB  - PURPOSE: Expressive syntax is a particular area of difficulty for individuals
      with Down syndrome (DS). In order to better understand the basis for sentence
      formulation deficits often observed in children and adults with DS, the authors
      explored the use and comprehension of verbs differing in argument structure.
      METHOD: The authors examined verb and argument structure retrieval in 18
      individuals, 9 with DS, age 11;11 (years;months) to 32;10 and 9 receptive
      vocabulary age-matched typically developing (TD) children, age 3;2 to 13;6.
      Participants completed verb and noun comprehension tasks, a working memory
      assessment, verb and noun naming tasks, grammaticality judgments, and narrative
      tasks. RESULTS: Neither single verb comprehension nor single verb naming
      differentiated the DS and TD groups. Individuals with DS performed significantly
      worse than individuals who are TD when asked to judge sentence grammaticality.
      Individuals with DS omitted verbs in elicited narratives significantly more often
      than individuals who are TD, specifically when productions of 2-place and 3-place
      verbs were attempted. Individuals with DS also omitted other necessary elements
      of argument structure, such as subjects, in sentences containing 2-place and 3
      place verbs significantly more often than individuals who are TD. Performance was
      not related to working memory skills. CONCLUSIONS: Results indicate that
      individuals with DS do display a specific expressive deficit in verb and argument
      structure retrieval (but not comprehension) that varies as a function of verb
      type (1 place, 2 place, and 3 place).

PMID- 22992706
TI  - Aerodynamic profiles of women with muscle tension dysphonia/aphonia.
AB  - PURPOSE: In this study, the authors aimed to (a) determine whether phonatory
      airflows and estimated subglottal pressures (est-Psub) for women with primary
      muscle tension dysphonia/aphonia (MTD/A) differ from those for healthy speakers;
      (b) identify different aerodynamic profile patterns within the MTD/A subject
      group; and (c) determine whether results suggest new understanding of
      pathogenesis in MTD/A. METHOD: Retrospective review of aerodynamic data collected
      from 90 women at the time of primary MTD/A diagnosis. RESULTS: Aerodynamic
      profiles were significantly different for women with MTD/A as compared with
      healthy speakers. Five distinct profiles were identified: (a) normal flow, normal
      est-Psub; (b) high flow, high est-Psub; (c) low flow, normal est-Psub; (d) normal
      flow, high est-Psub; and (e) high flow, normal est-Psub. CONCLUSIONS: This study
      is the first to identify distinct subgroups of aerodynamic profiles in women with
      MTD/A and to quantitatively identify a clinical phenomenon sometimes described in
      association with it-"breath holding"-that is shown by low airflow with normal est
      Psub. Results were consistent with clinical claims that diverse respiratory and
      laryngeal functions may underlie phonatory patterns associated with MTD/A. One
      potential mechanism, based in psychobiological theory, is introduced to explain
      some of the variability in aerodynamic profiles of women with MTD/A.

PMID- 22992707
TI  - Tense marking and spontaneous speech measures in Spanish specific language
      impairment: a discriminant function analysis.
AB  - PURPOSE: To test the proposal that the tense deficit that has been demonstrated
      for children with specific language impairment (SLI) in other languages is also
      found in child Spanish and that low performance on tense-related measures can
      distinguish Spanish-speaking children with SLI from those without. METHOD: The
      authors evaluated evidence from existing spontaneous production, elicited
      production, and grammaticality judgment studies of finiteness in child Spanish.
      They measured the relationship of 7 spontaneous speech measures with previous
      receptive and expressive measures of finiteness and performed a discriminant
      function analysis, using tense as the target variable, to classify monolingual
      child Spanish (n = 55) as representing SLI or as typically developing (TD).
      RESULTS: Spontaneous speech measures correlated with the results of previous
      receptive and expressive measures of child Spanish that show a tense deficit. The
      SLI group was shown to have statistically lower scores than the TD group on 6 of
      7 spontaneous speech measures. Multiple discriminant functions, including tense
      measures by themselves and in combination with spontaneous speech measures, were
      shown to provide fair to good sensitivity and specificity in the classification
      of children as having SLI vs. TD. CONCLUSION: The findings support the contention
      that the tense-marking deficit is a plausible clinical marker of SLI for Spanish
      speaking children.

PMID- 22992708
TI  - Semantic convergence in Spanish-English bilingual children with primary language
      impairment.
AB  - PURPOSE: To examine the degree of convergence in word association responses
      produced by bilingual children with primary language impairment (PLI) in relation
      to bilingual age peers. METHOD: Thirty-seven Spanish-English bilingual children
      with PLI, 37 typically developing (TD) controls, and a normative sample of 112
      children produced associations to 24 English and Spanish words. The 5 most
      frequent responses for each stimulus were identified for the normative sample;
      then the frequency of occurrence of these frequent normative responses was
      tabulated and compared between the PLI and TD groups. RESULTS: Children with PLI
      generated fewer frequent normative responses than their TD peers. Spearman rank
      correlations revealed that the rank frequency of responses in the normative group
      was significantly correlated with that of the TD and PLI groups; however, in
      English, the correlation was stronger for the TD cohort. Cross-language
      associations were also revealed in the generation of frequent norming responses.
      CONCLUSIONS: Semantic convergence is determined by multiple factors. Reduced
      production of frequent normative responses and weakened correlation with group
      association behavior in English suggest that children with PLI were delayed in
      converging on a central core of semantic knowledge that is characteristic of
      bilingual children with typical language skills.

PMID- 22992710
TI  - Audiovisual perception of congruent and incongruent Dutch front vowels.
AB  - PURPOSE: Auditory perception of vowels in background noise is enhanced when
      combined with visually perceived speech features. The objective of this study was
      to investigate whether the influence of visual cues on vowel perception extends
      to incongruent vowels, in a manner similar to the McGurk effect observed with
      consonants. METHOD: Identification of Dutch front vowels /i, y, e, Y/ that share
      all features other than height and lip-rounding was measured for congruent and
      incongruent audiovisual conditions. The audio channel was systematically degraded
      by adding noise, increasing the reliance on visual cues. RESULTS: The height
      feature was more robustly carried over through the auditory channel and the lip
      rounding feature through the visual channel. Hence, congruent audiovisual
      presentation enhanced identification, while incongruent presentation led to
      perceptual fusions and thus decreased identification. CONCLUSIONS: Visual cues
      influence the identification of congruent as well as incongruent audiovisual
      vowels. Incongruent visual information results in perceptual fusions,
      demonstrating that the McGurk effect can be instigated by long phonemes such as
      vowels. This result extends to the incongruent presentation of the visually less
      reliably perceived height. The findings stress the importance of audiovisual
      congruency in communication devices, such as cochlear implants and
      videoconferencing tools, where the auditory signal could be degraded.

PMID- 22992709
TI  - Word learning in adults with second-language experience: effects of phonological
      and referent familiarity.
AB  - PURPOSE: The goal of this research was to examine whether phonological
      familiarity exerts different effects on novel word learning for familiar versus
      unfamiliar referents and whether successful word learning is associated with
      increased second-language experience. METHOD: Eighty-one adult native English
      speakers with various levels of Spanish knowledge learned phonologically familiar
      novel words (constructed using English sounds) or phonologically unfamiliar novel
      words (constructed using non-English and non-Spanish sounds) in association with
      either familiar or unfamiliar referents. Retention was tested via a forced-choice
      recognition task. A median-split procedure identified high-ability and low
      ability word learners in each condition, and the two groups were compared on
      measures of second-language experience. RESULTS: Findings suggest that the
      ability to accurately match newly learned novel names to their appropriate
      referents is facilitated by phonological familiarity only for familiar referents
      but not for unfamiliar referents. Moreover, more extensive second-language
      learning experience characterized superior learners primarily in one word
      learning condition: in which phonologically unfamiliar novel words were paired
      with familiar referents. CONCLUSIONS: Together, these findings indicate that
      phonological familiarity facilitates novel word learning only for familiar
      referents and that experience with learning a second language may have a specific
      impact on novel vocabulary learning in adults.

PMID- 22992711
TI  - Individual variability in delayed auditory feedback effects on speech fluency and
      rate in normally fluent adults.
AB  - PURPOSE: Delayed auditory feedback (DAF) is known to induce stuttering-like
      disfluencies (SLDs) and cause speech rate reductions in normally fluent adults,
      but the reason for speech disruptions is not fully known, and individual
      variation has not been well characterized. Studying individual variation in
      susceptibility to DAF may identify factors that predispose an individual to be
      more or less dependent on auditory feedback. METHOD: Participants were 62
      normally fluent adults. Each participant performed a spontaneous speech task in
      250-ms DAF and amplified nondelayed auditory feedback (NAF) conditions. SLDs,
      other disfluencies (ODs), speech errors (SEs), and articulation rate (AR) were
      measured under each condition. RESULTS: In the DAF condition, SLDs and SEs
      significantly increased, and AR decreased. Sex had a limited effect in that men
      exhibited higher rates of ODs and faster AR than women. More important,
      parametric cluster analysis identified that 2- and 3-subgroup solutions reveal
      important variation that differentiates tendencies toward disfluency changes and
      rate reduction under DAF, which are theoretically and empirically preferred to a
      single-group solution. CONCLUSION: Individual variability in response to DAF may
      be accounted for by subgroups of individuals. This suggests that certain normally
      fluent individuals could be more dependent on intact feedback to maintain
      fluency.

PMID- 22992713
TI  - Gender differences in the link between excessive drinking and domain-specific
      cognitive functioning among older adults.
AB  - OBJECTIVE: This study investigated gender differences in the relationship between
      excessive drinking and two cognitive domains among older adults. METHOD: Using
      data from the Health and Retirement Study, 3,888 females and 2,350 males were
      analyzed separately. Multivariate regression was used to analyze the association
      between excessive drinking and fluid intelligence score. Logistic regression was
      conducted to examine the relationship between excessive drinking and crystallized
      intelligence. RESULTS: Multivariate analysis showed that compared to non
      excessive drinking, excessive drinking did not have a significant impact on fluid
      intelligence for either women or men, but it had a significantly negative
      association with a high crystallized intelligence score for women. DISCUSSION:
      Findings suggest that the relationship between excessive drinking and cognition
      varies with gender when crystallized intelligence is measured. Clinicians and
      service providers should consider gender differences when developing strategies
      for the prevention and treatment of alcohol-related cognitive decline among older
      adults.

PMID- 22992715
TI  - Health disparities in later life: a simultaneous equations analysis of
      utilization.
AB  - OBJECTIVE: This article examines health disparities between older Blacks/Whites
      by recognizing the importance of health services utilization. Although previous
      studies have examined health and utilization independently, this is among the
      first to (a) model its endogenous relation with utilization, and (b) use a
      continuous measure for health. DATA: Household Component files from Medical
      Expenditures Panel Survey (MEPS) from 2004 and 2005, with 1,369 observations
      (1,169 for White and 200 for Black) between the ages of 61-69. METHODS: The
      methods employed are two-equation modeling where Medicare eligibility functions
      as the identification criterion and also as an exogenous shock. RESULTS: The
      results show older Blacks continue to remain in poorer health despite access to
      care and insurance status. The author shows underutilization accounts for some of
      this observed disparity and offers novel approaches to overcome this issue.
      CONCLUSION: With the baby-boom cohort approaching retirement, this area of
      research is timely. This work is also practical because the Department of Health
      and Human Services has launched various projects examining health care issues for
      Americans. One major project, Healthy People 2010, provides a "framework for
      prevention for the Nation [and is] designed to identify the most significant
      preventable threats to health and to establish national goals to reduce these
      threats" (http://www.healthypeople.gov/About/). Of the 28 areas, this article
      complements objectives relating to (a) disability and secondary conditions, and
      (b) access to quality health services. This article also supports Healthy People
      2020, which sets a high priority on access to health care (one of 12 topic areas)
      and categorizes health disparities as part of the Leading Health Indicators
      Framework.

PMID- 22992714
TI  - Gender and racial disparities in driving cessation among older adults.
AB  - OBJECTIVES: To longitudinally examine gender and racial disparities in driving
      cessation among older adults. METHODS: Data came from the Advanced Cognitive
      Training for Independent and Vital Elderly (ACTIVE) Study (N = 1,789). Logistic
      generalized estimating equations (GEE) were used to identify predictors of
      driving cessation; stratified analysis and interaction terms were used to
      determine whether factors differed by gender and race. RESULTS: Two hundred and
      five (11.5%) participants stopped driving over the study period. Education was
      associated with increased risk of cessation for men (adjusted odds ratio [AOR]
      =1.40, 95% confidence interval [CI] =1.10 to 1.78), but decreased risk for women
      (AOR = 0.90, 95% CI = 0.82-0.98). Being married was associated with lower risk of
      cessation for men (AOR = 0.18, 95% CI = 0.06-0.56) but was unrelated to cessation
      for women (AOR = 1.00, 95% CI = 0.56-1.80). Results were consistent with the
      hypothesis that racial disparities in cessation widen with increasing age.
      DISCUSSION: Factors predictive of driving cessation vary by gender. Racial
      disparities in cessation are wider at older ages. Transportation policies and
      programs should account for social determinants and aim to address social
      disparities in driving mobility among older adults.

PMID- 22992716
TI  - A simplified purification method for AAV variant by polyethylene glycol aqueous
      two-phase partitioning.
AB  - Adeno-Associated Virus (AAV) has been widely used for in vivo study and
      preclinical therapy due to its ability to mediate long-term transgene expression,
      its lack of pathogenicity and low immunogenicity. It has been found that AAV has
      more than ten serotypes, which each transfect certain types of cells in the viral
      infected organ. Current methods for purification of different AAV serotypes
      utilize CsCl or Iodixanol ultrahigh speed density gradient centrifugation, which
      is expensive and time consuming. We recently developed a simplified method,
      PEG/(NH(4))(2)SO(4) aqueous two phase partitioning, for purification of AAV
      serotype 2 and 8. The method does not require ultrahigh speed gradient
      centrifugation or chromatography. Here we further explore the simplified method
      for purification of other serotypes of AAV, serotype 6 and 9. This simplified
      method not only can be used to purify serotype 2 and 8, but also serotype 6 and
      9, indicating that a variety of AAV serotypes can be purified by this method.

PMID- 22992717
TI  - Testing a fall risk model for injection drug users.
AB  - BACKGROUND: Fall risk is a critical component of clinical assessment and has not
      been examined for persons who have injected illicit drugs and are aging.
      OBJECTIVES: The aim of this study was to test and develop the Fall Risk Model for
      Injection Drug Users by examining the relationships among injection drug use,
      chronic venous insufficiency, lower extremity impairments (i.e., decreased ankle
      range of motion, reduced calf muscle endurance, and leg pain), age and other
      covariates, and the Tinetti balance and gait total score as a measure of fall
      risk. METHODS: A cross-sectional comparative design was used with four crossed
      factors. Standardized instruments were used to assess the variables. Moderated
      multiple regression with linear and quadratic trends in age was used to examine
      the nature of the relationship between the Tinetti balance and gait total and age
      and the potential moderating role of injection drug use. A prespecified series of
      models was tested. RESULTS: Participants (n = 713) were men (46.9%) and women
      with a mean age of 46.26 years and primarily African American (61.7%) in
      methadone treatment centers. The fall risk of a 48-year-old leg injector was
      comparable with the fall risk of a 69-year-old who had not injected drugs.
      Variables were added to the model sequentially, resulting in some lost
      significance of some when they were explained by subsequent variables. Final
      significant variables in the model were employment status, number of
      comorbidities, ankle range of motion, leg pain, and calf muscle endurance.
      DISCUSSION: Fall risk was associated with route of drug use. Lower extremity
      impairments accounted for the effects of injection drug use and chronic venous
      insufficiency on risk for falls. Further understanding of fall risk in injection
      users is necessary as they age, attempt to work, and participate in activities.

PMID- 22992718
TI  - Assessing the adsorption selectivity of linker functionalized, moisture-stable
      metal-organic framework thin films by means of an environment-controlled quartz
      crystal microbalance.
AB  - The stepwise thin film deposition of the robust, hydrophobic
      [Zn(4)O(dmcapz)(3)](n) (dmcapz = 3,5-dimethyl-4-carboxy-pyrazolato) is reported.
      The adsorption of small organic probe molecules, including alkanols, toluene,
      aniline and xylenes, was monitored by an environment-controlled quartz crystal
      microbalance setup. The adsorption selectivity was tuned by introducing alkyl
      side chains in the dmcapz linker.

PMID- 22992719
TI  - Awareness and its association with affective symptoms in young-onset and late
      onset Alzheimer disease: a prospective study.
AB  - BACKGROUND: It is unknown whether there are differences between young-onset
      dementia and late-onset dementia in awareness levels and whether awareness is
      differentially associated with affective symptoms in both groups. The present
      study assesses possible differences between young-onset (YO-AD) and late-onset
      Alzheimer disease (LO-AD) in awareness levels and the association between
      awareness and affective symptoms. METHODS: This study included 142 YO-AD and 126
      LO-AD patients and their caregivers from 2 prospective studies. The participants
      were assessed 3 times during 1 year. Awareness was assessed using the Guidelines
      for the Rating of Awareness Deficits, and affective symptoms were assessed using
      the anxiety and depression items of the Neuropsychiatric Inventory. Population
      averaged logistic regressions were used to analyze awareness and its association
      with affective symptoms. RESULTS: The odds for impaired awareness in LO-AD were
      more than double the odds in YO-AD. Intact awareness was associated with
      depressive symptoms but not with anxiety. This effect was more pronounced in YO
      AD compared with LO-AD at baseline. High awareness at baseline did not predict
      incident affective symptoms. CONCLUSIONS: Caregivers and clinicians should be
      prepared for affective symptoms in YO-AD patients with high awareness. The higher
      awareness in the YO-AD group also has potential positive implications for this
      group.

PMID- 22992720
TI  - Combining direct and proxy assessments to reduce attrition bias in a longitudinal
      study.
AB  - Retaining severely impaired individuals poses a major challenge in longitudinal
      studies of determinants of dementia or memory decline. In the Health and
      Retirement Study (HRS), participants complete direct memory assessments
      biennially until they are too impaired to complete the interview. Thereafter,
      proxy informants, typically spouses, assess the subject's memory and cognitive
      function using standardized instruments. Because there is no common scale for
      direct memory assessments and proxy assessments, proxy reports are often excluded
      from longitudinal analyses. The Aging, Demographics, and Memory Study (ADAMS)
      implemented full neuropsychological examinations on a subsample (n=856) of HRS
      participants, including respondents with direct or proxy cognitive assessments in
      the prior HRS core interview. Using data from the ADAMS, we developed an approach
      to estimating a dementia probability and a composite memory score on the basis of
      either proxy or direct assessments in HRS core interviews. The prediction model
      achieved a c-statistic of 94.3% for DSM diagnosed dementia in the ADAMS sample.
      We applied these scoring rules to HRS core sample respondents born 1923 or
      earlier (n=5483) for biennial assessments from 1995 to 2008. Compared with
      estimates excluding proxy respondents in the full cohort, incorporating
      information from proxy respondents increased estimated prevalence of dementia by
      12 percentage points in 2008 (average age=89) and suggested accelerated rates of
      memory decline over time. 

PMID- 22992721
TI  - The SLE-associated Pbx1-d isoform acts as a dominant-negative transcriptional
      regulator.
AB  - Pbx1 is a transcription factor involved in multiple cellular processes, including
      the maintenance of self-renewal of hematopoietic progenitors. We have shown that
      the CD4(+) T-cell expression of a novel splice isoform of Pbx1, Pbx1-d, is
      associated with lupus susceptibility in the NZM2410 mouse and in lupus patients.
      The function of Pbx1 in T cells is unknown, but the splicing out of the DNA
      binding domain in Pbx1-d predicts a dominant-negative function. In support of
      this hypothesis, we have shown that Pbx1-d transduction accelerates
      differentiation of MC3T3-E1 osteoblast pregenitors and mimics the effect of short
      hairpin RNA silencing of Pbx1. Conversely, Pbx1-d transduction reduced the
      expression of Sox3, a gene strongly transactivated by Pbx1, and Pbx1-d did not
      bind the Sox3 promoter. These results constitute a first step towards the
      understanding on how Pbx1-d contributes to systemic autoimmunity in the NZM2410
      mouse model as well as in lupus patients.

PMID- 22992722
TI  - Host gene-encoded severe lung TB: from genes to the potential pathways.
AB  - We are reporting that the two-locus genotype -2518 macrophage chemoattractant
      protein (MCP)-1 GG and -1607 matrix metalloproteinase (MMP)-1 2G/2G promotes the
      expression of hyperinflammation in response to Mycobacterium tuberculosis
      infection, inducing extensive tissue damage and severe tuberculosis (TB) disease.
      Carriers of this two-locus genotype have a 13-fold higher chance of developing
      severe disease and 6.5-fold higher chance of developing permanent lesions, and a
      3.864-fold higher chance of delayed response to first-line standardized treatment
      than carriers of any other relevant combination of genotypes at those two loci.
      Thus, these persons have an increased likelihood of poor health-related quality
      of life and of transmitting M. tuberculosis to other members of the community. In
      addition, through the analysis of human lung tissues, serum/plasma and in vitro
      experiments, including in vitro infections of THP-1 cells with M. tuberculosis
      and microarray analysis, we determined that this hyperinflammation state is
      potentially driven by the MCP-1/MMP-1/PAR-1 pathway. Hence, we are providing
      markers for the identification of TB cases that may develop severe pulmonary
      disease and delayed response to treatment, and are providing the basis for
      development of novel host-targeted clinical interventions to ameliorate the
      severity of pulmonary TB.

PMID- 22992723
TI  - Omega-3 fatty acids in ileal effluent after consuming different foods containing
      microencapsulated fish oil powder - an ileostomy study.
AB  - The intestinal absorption of omega-3 long chain polyunsaturated fatty acids
      (omega3 LCPUFA), [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)],
      after consuming fish oil gelatine capsules or different food products fortified
      with microencapsulated fish oil, was determined using human ileostomates. The
      total amount of omega3 LCPUFA consumed per dose of fish oil capsule was 266 mg
      while that for fortified orange juice, yoghurt and cereal bar was 284 mg per
      serving of food product. In a time course experiment omega3 LCPUFA was measured
      in ileal effluent over 24 h post ingestion. Only 0.58-0.73% of the total omega3
      LCPUFA dose was recovered in the ileal effluent irrespective of whether the fish
      oil was delivered in a gelatine capsule or in the form of a microencapsulated
      powder incorporated into fortified foods. Excretion of omega3 LCPUFA was detected
      in the 2-18 h effluent collections with none detected at 0 h or 24 h. post
      ingestion. The transit time of the minimal amount of omega3 LCPUFA that remained
      in the ileal effluent was dependent on the method of delivery of the fish oil.
      The omega3 LCPUFA content in the ileal effluent peaked at 2-8 h and declined
      after 10 h after consumption of fish oil capsules and fortified orange juice. In
      contrast, two peaks in omega3 LCPUFA content were observed in the ileal effluent,
      first at 2-8 h and again at 14-16 h, after consumption of fortified yoghurt and
      cereal bar. The highest recovery of the small amount of omega3 LCPUFA in the
      ileal effluent at 14-16 h was obtained when fortified cereal bar was consumed.
      The results suggest that the delivery of fish oil through food products fortified
      with microencapsulated fish oil does not compromise the bioavailability of the
      omega3 LCPUFA as evidence by no statistical differences detected in the remaining
      portion of omega3 LCPUFA in the ileal effluent (p = 0.58). However, the food
      matrix in which the microencapsulated oil was delivered may alter the transit
      kinetics of the omega3 LCPUFA through the small intestine.

PMID- 22992724
TI  - Bambusae Caulis in Taeniam modulates neuroprotective and anti-neuroinflammatory
      effects in hippocampal and microglial cells via HO-1- and Nrf-2-mediated
      pathways.
AB  - Recent evidence indicates that microglial activation and hippocampal damage may
      play important roles in neurodegenerative diseases, including Alzheimer's
      disease. Bambusae Caulis in Taeniam has been used as a folk remedy for the
      treatment of hypertension and cardiovascular disease in China and Korea. In this
      study, the mechanism responsible for the neuroprotective and anti
      neuroinflammatory effects of Bambusae Caulis in Taeniam ethyl acetate fraction
      (BCE) was investigated. Heme oxygenase-1 (HO-1) is an inducible enzyme expressed
      in response to various inflammatory stimuli. Due to its role in the anti
      inflammatory signaling pathway, the expression and modulation of HO-1 are
      important. In this study, the neuroprotective and anti-neuroinflammatory effects
      of BCE were examined using the murine microglial BV2 and hippocampal HT22 cells.
      We demonstrated that the administration of BCE provided neuroprotective effects
      against glutamate-induced cytotoxicity in HT22 cells through the HO-1 and nuclear
      erythroid-2 related factor 2 (Nrf-2) signaling pathways. We also reported that
      BCE inhibited lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and
      that the presence of selective inhibitors of HO-1 (SnPP) resulted in the
      inhibition of BCE-mediated anti-inflammatory activity in BV2 microglial cells.
      BCE was shown to induce HO-1 expression as well as the nuclear translocation of
      Nrf-2 in both microglial and hippocampal cells. These findings revealed the
      potential therapeutic mechanisms of BCE in neurodegenerative diseases, suggesting
      that HO-1 and Nrf-2 signaling may play important roles in the mediation of its
      neuroprotective and anti-neuroinflammatory effects.

PMID- 22992725
TI  - Elevated SP-1 transcription factor expression and activity drives basal and
      hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small
      cell lung cancer.
AB  - VEGF plays a central role in angiogenesis in cancer. Non-small cell lung cancer
      (NSCLC) tumors have increased microvascular density, localized hypoxia, and high
      VEGF expression levels; however, there is a lack of understanding of how
      oncogenic and tumor microenvironment changes such as hypoxia lead to greater VEGF
      expression in lung and other cancers. We show that NSCLC cells secreted higher
      levels of VEGF than normal airway epithelial cells. Actinomycin D inhibited all
      NSCLC VEGF secretion, and VEGF minimal promoter-luciferase reporter constructs
      were constitutively active until the last 85 base pairs before the transcription
      start site containing three SP-1 transcription factor-binding sites; mutation of
      these VEGF promoter SP-1-binding sites eliminated VEGF promoter activity.
      Furthermore, dominant negative SP-1, mithramycin A, and SP-1 shRNA decreased VEGF
      promoter activity, whereas overexpression of SP-1 increased VEGF promoter
      activity. Chromatin immunoprecipitation assays demonstrated SP-1, p300, and PCA/F
      histone acetyltransferase binding and histone H4 hyperacetylation at the VEGF
      promoter in NSCLC cells. Cultured NSCLC cells expressed higher levels of SP-1
      protein than normal airway epithelial cells, and double-fluorescence
      immunohistochemistry showed a strong correlation between SP-1 and VEGF in human
      NSCLC tumors. In addition, hypoxia-driven VEGF expression in NSCLC cells was SP-1
      dependent, with hypoxia increasing SP-1 activity and binding to the VEGF
      promoter. These studies are the first to demonstrate that overexpression of SP-1
      plays a central role in hypoxia-induced VEGF secretion.

PMID- 22992726
TI  - The SAGA histone acetyltransferase complex regulates leucine uptake through the
      Agp3 permease in fission yeast.
AB  - Metabolic responses of unicellular organisms are mostly acute, transient, and
      cell-autonomous. Regulation of nutrient uptake in yeast is one such rapid
      response. High quality nitrogen sources such as NH(4)(+) inhibit uptake of poor
      nitrogen sources, such as amino acids. Both transcriptional and
      posttranscriptional mechanisms operate in nutrient uptake regulation; however,
      many components of this system remain uncharacterized in the fission yeast,
      Schizosaccharomyces pombe. Here, we demonstrate that the Spt-Ada-Gcn
      acetyltransferase (SAGA) complex modulates leucine uptake. Initially, we noticed
      that a branched-chain amino acid auxotroph exhibits a peculiar adaptive growth
      phenotype on solid minimal media containing certain nitrogen sources. In fact,
      the growth of many auxotrophic strains is inhibited by excess NH(4)Cl, possibly
      through nitrogen-mediated uptake inhibition of the corresponding nutrients.
      Surprisingly, DNA microarray analysis revealed that the transcriptional
      reprogramming during the adaptation of the branched-chain amino acid auxotroph
      was highly correlated with reprogramming observed in deletions of the SAGA
      histone acetyltransferase module genes. Deletion of gcn5(+) increased leucine
      uptake in the prototrophic background and rendered the leucine auxotroph
      resistant to NH(4)Cl. Deletion of tra1(+) caused the opposite phenotypes. The
      increase in leucine uptake in the gcn5Delta mutant was dependent on an amino acid
      permease gene, SPCC965.11c(+). The closest budding yeast homolog of this permease
      is a relatively nonspecific amino acid permease AGP3, which functions in poor
      nutrient conditions. Our analysis identified the regulation of nutrient uptake as
      a physiological function for the SAGA complex, providing a potential link between
      cellular metabolism and chromatin regulation.

PMID- 22992727
TI  - Isorhamnetin inhibits proliferation and invasion and induces apoptosis through
      the modulation of peroxisome proliferator-activated receptor gamma activation
      pathway in gastric cancer.
AB  - Gastric cancer (GC) is a lethal malignancy and the second most common cause of
      cancer-related deaths. Although treatment options such as chemotherapy,
      radiotherapy, and surgery have led to a decline in the mortality rate due to GC,
      chemoresistance remains as one of the major causes for poor prognosis and high
      recurrence rate. In this study, we investigated the potential effects of
      isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin on the peroxisome
      proliferator-activated receptor gamma (PPAR-gamma) signaling cascade using
      proteomics technology platform, GC cell lines, and xenograft mice model. We
      observed that IH exerted a strong antiproliferative effect and increased
      cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the
      migratory/invasive properties of GC cells, which could be reversed in the
      presence of PPAR-gamma inhibitor. We found that IH increased PPAR-gamma activity
      and modulated the expression of PPAR-gamma regulated genes in GC cells. Also, the
      increase in PPAR-gamma activity was reversed in the presence of PPAR-gamma
      specific inhibitor and a mutated PPAR-gamma dominant negative plasmid, supporting
      our hypothesis that IH can act as a ligand of PPAR-gamma. Using molecular docking
      analysis, we demonstrate that IH formed interactions with seven polar residues
      and six nonpolar residues within the ligand-binding pocket of PPAR-gamma that are
      reported to be critical for its activity and could competitively bind to PPAR
      gamma. IH significantly increased the expression of PPAR-gamma in tumor tissues
      obtained from xenograft model of GC. Overall, our findings clearly indicate that
      antitumor effects of IH may be mediated through modulation of the PPAR-gamma
      activation pathway in GC.

PMID- 22992728
TI  - Modification of STIM1 by O-linked N-acetylglucosamine (O-GlcNAc) attenuates store
      operated calcium entry in neonatal cardiomyocytes.
AB  - Store-operated calcium entry (SOCE) is a major Ca(2+) signaling pathway
      responsible for regulating numerous transcriptional events. In cardiomyocytes
      SOCE has been shown to play an important role in regulating hypertrophic
      signaling pathways, including nuclear translocation of NFAT. Acute activation of
      pathways leading to O-GlcNAc synthesis have been shown to impair SOCE-mediated
      transcription and in diabetes, where O-GlcNAc levels are chronically elevated,
      cardiac hypertrophic signaling is also impaired. Therefore the goal of this study
      was to determine whether changes in cardiomyocyte O-GlcNAc levels impaired the
      function of STIM1, a widely recognized mediator of SOCE. We demonstrated that
      acute activation of SOCE in neonatal cardiomyocytes resulted in STIM1 puncta
      formation, which was inhibited in a dose-dependent manner by increasing O-GlcNAc
      synthesis with glucosamine or inhibiting O-GlcNAcase with thiamet-G. Glucosamine
      and thiamet-G also inhibited SOCE and were associated with increased O-GlcNAc
      modification of STIM1. These results suggest that activation of cardiomyocyte O
      GlcNAcylation attenuates SOCE via STIM1 O-GlcNAcylation and that this may
      represent a new mechanism by which increased O-GlcNAc levels regulate Ca(2+)
      mediated events in cardiomyocytes. Further, since SOCE is a fundamental mechanism
      underlying Ca(2+) signaling in most cells and tissues, it is possible that STIM1
      represents a nexus linking protein O-GlcNAcylation with Ca(2+)-mediated
      transcription.

PMID- 22992729
TI  - Identification of the cysteine residue responsible for disulfide linkage of Na+
      channel alpha and beta2 subunits.
AB  - Voltage-gated Na(+) channels in the brain are composed of a single pore-forming
      alpha subunit, one non-covalently linked beta subunit (beta1 or beta3), and one
      disulfide-linked beta subunit (beta2 or beta4). The final step in Na(+) channel
      biosynthesis in central neurons is concomitant alpha-beta2 disulfide linkage and
      insertion into the plasma membrane. Consistent with this, Scn2b (encoding beta2)
      null mice have reduced Na(+) channel cell surface expression in neurons, and
      action potential conduction is compromised. Here we generated a series of mutant
      beta2 cDNA constructs to investigate the cysteine residue(s) responsible for
      alpha-beta2 subunit covalent linkage. We demonstrate that a single cysteine-to
      alanine substitution at extracellular residue Cys-26, located within the
      immunoglobulin (Ig) domain, abolishes the covalent linkage between alpha and
      beta2 subunits. Loss of alpha-beta2 covalent complex formation disrupts the
      targeting of beta2 to nodes of Ranvier in a myelinating co-culture system and to
      the axon initial segment in primary hippocampal neurons, suggesting that linkage
      with alpha is required for normal beta2 subcellular localization in vivo. WT
      beta2 subunits are resistant to live cell Triton X-100 detergent extraction from
      the hippocampal axon initial segment, whereas mutant beta2 subunits, which cannot
      form disulfide bonds with alpha, are removed by detergent. Taken together, our
      results demonstrate that alpha-beta2 covalent association via a single,
      extracellular disulfide bond is required for beta2 targeting to specialized
      neuronal subcellular domains and for beta2 association with the neuronal
      cytoskeleton within those domains.

PMID- 22992730
TI  - Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptors trigger neuronal nitric-oxide synthase activation to promote nerve cell
      death in an Src kinase-dependent fashion.
AB  - In the retina information decoding is dependent on excitatory neurotransmission
      and is critically modulated by AMPA glutamate receptors. The Src-tyrosine kinase
      has been implicated in modulating neurotransmission in CNS. Thus, our main goal
      was to correlate AMPA-mediated excitatory neurotransmission with the modulation
      of Src activity in retinal neurons. Cultured retinal cells were used to access
      the effects of AMPA stimulation on nitric oxide (NO) production and Src
      phosphorylation. 4-Amino-5-methylamino-2',7'-difluorofluorescein diacetate
      fluorescence mainly determined NO production, and immunocytochemistry and Western
      blotting evaluated Src activation. AMPA receptors activation rapidly up-regulated
      Src phosphorylation at tyrosine 416 (stimulatory site) and down-regulated
      phosphotyrosine 527 (inhibitory site) in retinal cells, an effect mainly mediated
      by calcium-permeable AMPA receptors. Interestingly, experiments confirmed that
      neuronal NOS was activated in response to calcium-permeable AMPA receptor
      stimulation. Moreover, data suggest NO pathway as a key regulatory signaling in
      AMPA-induced Src activation in neurons but not in glial cells. The NO donor SNAP
      (S-nitroso-N-acetyl-DL-penicillamine) and a soluble guanylyl cyclase agonist (YC
      1) mimicked AMPA effect in Src Tyr-416 phosphorylation, reinforcing that Src
      activation is indeed modulated by the NO pathway. Gain and loss-of-function data
      demonstrated that ERK is a downstream target of AMPA-induced Src activation and
      NO signaling. Furthermore, AMPA stimulated NO production in organotypic retinal
      cultures and increased Src activity in the in vivo retina. Additionally, AMPA
      induced apoptotic retinal cell death was regulated by both NOS and Src activity.
      Because Src activity is pivotal in several CNS regions, the data presented herein
      highlight that Src modulation is a critical step in excitatory retinal cell
      death.

PMID- 22992731
TI  - A novel inhibitor of amyloid beta (Abeta) peptide aggregation: from high
      throughput screening to efficacy in an animal model of Alzheimer disease.
AB  - Compelling evidence indicates that aggregation of the amyloid beta (Abeta)
      peptide is a major underlying molecular culprit in Alzheimer disease.
      Specifically, soluble oligomers of the 42-residue peptide (Abeta42) lead to a
      series of events that cause cellular dysfunction and neuronal death. Therefore,
      inhibiting Abeta42 aggregation may be an effective strategy for the prevention
      and/or treatment of disease. We describe the implementation of a high throughput
      screen for inhibitors of Abeta42 aggregation on a collection of 65,000 small
      molecules. Among several novel inhibitors isolated by the screen, compound D737
      was most effective in inhibiting Abeta42 aggregation and reducing Abeta42-induced
      toxicity in cell culture. The protective activity of D737 was most significant in
      reducing the toxicity of high molecular weight oligomers of Abeta42. The ability
      of D737 to prevent Abeta42 aggregation protects against cellular dysfunction and
      reduces the production/accumulation of reactive oxygen species. Most importantly,
      treatment with D737 increases the life span and locomotive ability of flies in a
      Drosophila melanogaster model of Alzheimer disease.

PMID- 22992732
TI  - The interaction between polynucleotide kinase phosphatase and the DNA repair
      protein XRCC1 is critical for repair of DNA alkylation damage and stable
      association at DNA damage sites.
AB  - XRCC1 plays a key role in the repair of DNA base damage and single-strand breaks.
      Although it has no known enzymatic activity, XRCC1 interacts with multiple DNA
      repair proteins and is a subunit of distinct DNA repair protein complexes. Here
      we used the yeast two-hybrid genetic assay to identify mutant versions of XRCC1
      that are selectively defective in interacting with a single protein partner. One
      XRCC1 mutant, A482T, that was defective in binding to polynucleotide kinase
      phosphatase (PNKP) not only retained the ability to interact with partner
      proteins that bind to different regions of XRCC1 but also with aprataxin and
      aprataxin-like factor whose binding sites overlap with that of PNKP. Disruption
      of the interaction between PNKP and XRCC1 did not impact their initial
      recruitment to localized DNA damage sites but dramatically reduced their
      retention there. Furthermore, the interaction between PNKP and the DNA ligase
      IIIalpha-XRCC1 complex significantly increased the efficiency of reconstituted
      repair reactions and was required for complementation of the DNA damage
      sensitivity to DNA alkylation agents of xrcc1 mutant cells. Together our results
      reveal novel roles for the interaction between PNKP and XRCC1 in the retention of
      XRCC1 at DNA damage sites and in DNA alkylation damage repair.

PMID- 22992733
TI  - Arginine transcriptional response does not require inositol phosphate synthesis.
AB  - Inositol phosphates are key signaling molecules affecting a large variety of
      cellular processes. Inositol-polyphosphate multikinase (IPMK) is a central
      component of the inositol phosphate biosynthetic routes, playing essential roles
      during development. IPMK phosphorylates inositol 1,4,5-trisphosphate to inositol
      tetrakisphosphate and subsequently to inositol pentakisphosphate and has also
      been described to function as a lipid kinase. Recently, a catalytically inactive
      mammalian IPMK was reported to be involved in nutrient signaling by way of
      mammalian target of rapamycin and AMP-activated protein kinase. In yeast, the
      IPMK homologue, Arg82, is the sole inositol-trisphosphate kinase. Arg82 has been
      extensively studied as part of the transcriptional complex regulating nitrogen
      sensing, in particular arginine metabolism. Whether this role requires Arg82
      catalytic activity has long been a matter of contention. In this study, we
      developed a novel method for the real time study of promoter strength in vivo and
      used it to demonstrate that catalytically inactive Arg82 fully restored the
      arginine-dependent transcriptional response. We also showed that expression in
      yeast of catalytically active, but structurally very different, mammalian or
      plant IPMK homologue failed to restore arginine regulation. Our work indicates
      that inositol phosphates do not regulate arginine-dependent gene expression.

PMID- 22992734
TI  - Direct tests of enzymatic heme degradation by the malaria parasite Plasmodium
      falciparum.
AB  - Malaria parasites generate vast quantities of heme during blood stage infection
      via hemoglobin digestion and limited de novo biosynthesis, but it remains unclear
      if parasites metabolize heme for utilization or disposal. Recent in vitro
      experiments with a heme oxygenase (HO)-like protein from Plasmodium falciparum
      suggested that parasites may enzymatically degrade some heme to the canonical HO
      product, biliverdin (BV), or its downstream metabolite, bilirubin (BR). To
      directly test for BV and BR production by P. falciparum parasites, we DMSO
      extracted equal numbers of infected and uninfected erythrocytes and developed a
      sensitive LC-MS/MS assay to quantify these tetrapyrroles. We found comparable low
      levels of BV and BR in both samples, suggesting the absence of HO activity in
      parasites. We further tested live parasites by targeted expression of a
      fluorescent BV-binding protein within the parasite cytosol, mitochondrion, and
      plant-like plastid. This probe could detect exogenously added BV but gave no
      signal indicative of endogenous BV production within parasites. Finally, we
      recombinantly expressed and tested the proposed heme degrading activity of the HO
      like protein, PfHO. Although PfHO bound heme and protoporphyrin IX with modest
      affinity, it did not catalyze heme degradation in vivo within bacteria or in
      vitro in UV absorbance and HPLC assays. These observations are consistent with
      PfHO's lack of a heme-coordinating His residue and suggest an alternative
      function within parasites. We conclude that P. falciparum parasites lack a
      canonical HO pathway for heme degradation and thus rely fully on alternative
      mechanisms for heme detoxification and iron acquisition during blood stage
      infection.

PMID- 22992736
TI  - Suppression of electron transfer to dioxygen by charge transfer and electron
      transfer complexes in the FAD-dependent reductase component of toluene
      dioxygenase.
AB  - The three-component toluene dioxygenase system consists of an FAD-containing
      reductase, a Rieske-type [2Fe-2S] ferredoxin, and a Rieske-type dioxygenase. The
      task of the FAD-containing reductase is to shuttle electrons from NADH to the
      ferredoxin, a reaction the enzyme has to catalyze in the presence of dioxygen. We
      investigated the kinetics of the reductase in the reductive and oxidative half
      reaction and detected a stable charge transfer complex between the reduced
      reductase and NAD(+) at the end of the reductive half-reaction, which is
      substantially less reactive toward dioxygen than the reduced reductase in the
      absence of NAD(+). A plausible reason for the low reactivity toward dioxygen is
      revealed by the crystal structure of the complex between NAD(+) and reduced
      reductase, which shows that the nicotinamide ring and the protein matrix shield
      the reactive C4a position of the isoalloxazine ring and force the tricycle into
      an atypical planar conformation, both factors disfavoring the reaction of the
      reduced flavin with dioxygen. A rapid electron transfer from the charge transfer
      complex to electron acceptors further reduces the risk of unwanted side
      reactions, and the crystal structure of a complex between the reductase and its
      cognate ferredoxin shows a short distance between the electron-donating and 
      accepting cofactors. Attraction between the two proteins is likely mediated by
      opposite charges at one large patch of the complex interface. The stability,
      specificity, and reactivity of the observed charge transfer and electron transfer
      complexes are thought to prevent the reaction of reductase(TOL) with dioxygen and
      thus present a solution toward conflicting requirements.

PMID- 22992735
TI  - Certhrax toxin, an anthrax-related ADP-ribosyltransferase from Bacillus cereus.
AB  - We identified Certhrax, the first anthrax-like mART toxin from the pathogenic
      G9241 strain of Bacillus cereus. Certhrax shares 31% sequence identity with
      anthrax lethal factor from Bacillus anthracis; however, we have shown that the
      toxicity of Certhrax resides in the mART domain, whereas anthrax uses a
      metalloprotease mechanism. Like anthrax lethal factor, Certhrax was found to
      require protective antigen for host cell entry. This two-domain enzyme was shown
      to be 60-fold more toxic to mammalian cells than anthrax lethal factor. Certhrax
      localizes to distinct regions within mouse RAW264.7 cells by 10 min postinfection
      and is extranuclear in its cellular location. Substitution of catalytic residues
      shows that the mART function is responsible for the toxicity, and it binds NAD(+)
      with high affinity (K(D) = 52.3 +/- 12.2 MUM). We report the 2.2 A Certhrax
      structure, highlighting its structural similarities and differences with anthrax
      lethal factor. We also determined the crystal structures of two good inhibitors
      (P6 (K(D) = 1.7 +/- 0.2 MUM, K(i) = 1.8 +/- 0.4 MUM) and PJ34 (K(D) = 5.8 +/- 2.6
      MUM, K(i) = 9.6 +/- 0.3 MUM)) in complex with Certhrax. As with other toxins in
      this family, the phosphate-nicotinamide loop moves toward the NAD(+) binding site
      with bound inhibitor. These results indicate that Certhrax may be important in
      the pathogenesis of B. cereus.

PMID- 22992737
TI  - Matrix metalloproteinase-13 (MMP-13) directly and indirectly promotes tumor
      angiogenesis.
AB  - Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases
      involved in the degradation and remodeling of extracellular matrix in
      physiological and pathological processes. MMPs also have a role in cell
      proliferation, migration, differentiation, angiogenesis, and apoptosis. We
      previously identified cancer invasion-related factors by comparing the gene
      expression profiles between parent and the highly invasive clone of cancer cells.
      Matrix metalloproteinase-13 (MMP-13) was identified as a common up-regulated gene
      by cancer invasion-related factors. Although MMP-13 slightly promoted tumor
      invasion, we found that MMP-13 was involved in tumor angiogenesis. Conditioned
      medium from MMP-13-overexpressing cells promoted capillary formation of
      immortalized human umbilical vein endothelial cells. Furthermore, treatment with
      recombinant MMP-13 protein enhanced capillary tube formation both in vitro and in
      vivo. MMP-13-promoted capillary tube formation was mediated by activation of
      focal adhesion kinase and ERK. Interestingly, MMP-13 promoted the secretion of
      VEGF-A from fibroblasts and endothelial cells. By immunohistochemical analysis,
      we found a possible correlation between MMP-13 expression and the number of blood
      vessels in human cancer cases. In summary, these findings suggest that MMP-13 may
      directly and indirectly promote tumor angiogenesis.

PMID- 22992738
TI  - Inactivation of MARK4, an AMP-activated protein kinase (AMPK)-related kinase,
      leads to insulin hypersensitivity and resistance to diet-induced obesity.
AB  - MARK4, also known as Par-1d/MarkL1, is a member of the AMP-activated protein
      kinase (AMPK)-related family of kinases, which are implicated in the regulation
      of dynamic biological functions, including glucose and energy homeostasis.
      However, the physiological function of MARK4 in mammals remains elusive. Here, we
      investigated a role for MARK4 in regulating energy homeostasis by generating mice
      with targeted inactivation of the mark4 gene. We show that MARK4 deficiency in
      mice caused hyperphagia, hyperactivity, and hypermetabolism, leading to
      protection from diet-induced obesity and its related metabolic complications
      through up-regulation of brown fat activity. Consequently, MARK4 deficiency
      mitigated insulin resistance associated with diet-induced obesity by dramatically
      enhancing insulin-stimulated AKT phosphorylation in major metabolic tissues.
      Ablation of MARK4 also significantly improved glucose homeostasis by up
      regulating the activity and expression of AMPK kinase in key metabolic tissues.
      Taken together, these data identify a key role of MARK4 in energy metabolism,
      implicating the kinase as a novel drug target for the treatment of obesity and
      type 2 diabetes.

PMID- 22992739
TI  - Identification of a role for CLASP2 in insulin action.
AB  - Insulin stimulates the mobilization of glucose transporter 4 (GLUT4) storage
      vesicles to the plasma membrane, resulting in an influx of glucose into target
      tissues such as muscle and fat. We present evidence that CLIP-associating protein
      2 (CLASP2), a protein previously unassociated with insulin action, is responsive
      to insulin stimulation. Using mass spectrometry-based protein identification
      combined with phosphoantibody immunoprecipitation in L6 myotubes, we detected a
      4.8-fold increase of CLASP2 in the anti-phosphoserine immunoprecipitates upon
      insulin stimulation. Western blotting of CLASP2 immunoprecipitates with the
      phosphoantibody confirmed the finding that CLASP2 undergoes insulin-stimulated
      phosphorylation, and a number of novel phosphorylation sites were identified.
      Confocal imaging of L6 myotubes revealed that CLASP2 colocalizes with GLUT4 at
      the plasma membrane within areas of insulin-mediated cortical actin remodeling.
      CLASP2 is responsible for directing the distal end of microtubules to the cell
      cortex, and it has been shown that GLUT4 travels along microtubule tracks. In
      support of the concept that CLASP2 plays a role in the trafficking of GLUT4 at
      the cell periphery, CLASP2 knockdown by siRNA in L6 myotubes interfered with
      insulin-stimulated GLUT4 localization to the plasma membrane. Furthermore, siRNA
      mediated knockdown of CLASP2 in 3T3-L1 adipocytes inhibited insulin-stimulated
      glucose transport. We therefore propose a new model for CLASP2 in insulin action,
      where CLASP2 directs the delivery of GLUT4 to cell cortex landing zones important
      for insulin action.

PMID- 22992740
TI  - R753Q polymorphism inhibits Toll-like receptor (TLR) 2 tyrosine phosphorylation,
      dimerization with TLR6, and recruitment of myeloid differentiation primary
      response protein 88.
AB  - The R753Q polymorphism in the Toll-IL-1 receptor domain of Toll-like receptor 2
      (TLR2) has been linked to increased incidence of tuberculosis and other
      infectious diseases, but the mechanisms by which it affects TLR2 functions are
      unclear. Here, we studied the impact of the R753Q polymorphism on TLR2
      expression, hetero-dimerization with TLR6, tyrosine phosphorylation, and
      recruitment of myeloid differentiation primary response protein (MyD) 88 and
      MyD88 adapter-like (Mal). Complementation of HEK293 cells with transfected WT or
      R753Q TLR2 revealed their comparable total levels and only minimal changes in
      cell surface expression of the mutant species. Notably, even a 100-fold increase
      in amounts of transfected R753Q TLR2 versus WT variant did not overcome the
      compromised ability of the mutant TLR2 to activate nuclear factor kappaB (NF
      kappaB), indicating that a minimal decrease in cell surface levels of the R753Q
      TLR2 cannot account for the signaling deficiency. Molecular modeling studies
      suggested that the R753Q mutation changes the electrostatic potential of the DD
      loop and results in a discrete movement of the residues critical for protein
      protein interactions. Confirming these predictions, biochemical assays
      demonstrated that R753Q TLR2 exhibits deficient agonist-induced tyrosine
      phosphorylation, hetero-dimerization with TLR6, and recruitment of Mal and MyD88.
      These proximal signaling deficiencies correlated with impaired capacities of the
      R753Q TLR2 to mediate p38 phosphorylation, NF-kappaB activation, and induction of
      IL-8 mRNA in transfected HEK293 cells challenged with inactivated Mycobacterium
      tuberculosis or mycobacterial components. Thus, the R753Q polymorphism renders
      TLR2 signaling-incompetent by impairing its tyrosine phosphorylation,
      dimerization with TLR6, and recruitment of Mal and MyD88.

PMID- 22992741
TI  - The archaeal proteasome is regulated by a network of AAA ATPases.
AB  - The proteasome is the central machinery for targeted protein degradation in
      archaea, Actinobacteria, and eukaryotes. In its basic form, it consists of a
      regulatory ATPase complex and a proteolytic core particle. The interaction
      between the two is governed by an HbYX motif (where Hb is a hydrophobic residue,
      Y is tyrosine, and X is any amino acid) at the C terminus of the ATPase subunits,
      which stimulates gate opening of the proteasomal alpha-subunits. In archaea, the
      proteasome-interacting motif is not only found in canonical proteasome-activating
      nucleotidases of the PAN/ARC/Rpt group, which are absent in major archaeal
      lineages, but also in proteins of the CDC48/p97/VAT and AMA groups, suggesting a
      regulatory network of proteasomal ATPases. Indeed, Thermoplasma acidophilum,
      which lacks PAN, encodes one CDC48 protein that interacts with the 20S proteasome
      and activates the degradation of model substrates. In contrast, Methanosarcina
      mazei contains seven AAA proteins, five of which, both PAN proteins, two out of
      three CDC48 proteins, and the AMA protein, function as proteasomal gatekeepers.
      The prevalent presence of multiple, distinct proteasomal ATPases in archaea thus
      results in a network of regulatory ATPases that may widen the substrate spectrum
      of proteasomal protein degradation.

PMID- 22992742
TI  - Rho isoform-specific interaction with IQGAP1 promotes breast cancer cell
      proliferation and migration.
AB  - We performed a proteomics screen for Rho isoform-specific binding proteins to
      clarify the tumor-promoting effects of RhoA and C that contrast with the tumor
      suppressive effects of RhoB. We found that the IQ-motif-containing GTPase
      activating protein IQGAP1 interacts directly with GTP-bound, prenylated RhoA and
      RhoC, but not with RhoB. Co-immunoprecipitation of IQGAP1 with endogenous RhoA/C
      was enhanced when RhoA/C were activated by epidermal growth factor (EGF) or
      transfection of a constitutively active guanine nucleotide exchange factor (GEF).
      Overexpression of IQGAP1 increased GTP-loading of RhoA/C, while siRNA-mediated
      depletion of IQGAP1 prevented endogenous RhoA/C activation by growth factors.
      IQGAP1 knockdown also reduced the amount of GTP bound to GTPase-deficient RhoA/C
      mutants, suggesting that IQGAP enhances Rho activation by GEF(s) or stabilizes
      Rho-GTP. IQGAP1 depletion in MDA-MB-231 breast cancer cells blocked EGF- and RhoA
      induced stimulation of DNA synthesis. Infecting cells with adenovirus encoding
      constitutively active RhoA(L63) and measuring absolute amounts of RhoA-GTP in
      infected cells demonstrated that the lack of RhoA(L63)-induced DNA synthesis in
      IQGAP1-depleted cells was not due to reduced GTP-bound RhoA. These data suggested
      that IQGAP1 functions downstream of RhoA. Overexpression of IQGAP1 in MDA-MB-231
      cells increased DNA synthesis irrespective of siRNA-mediated RhoA knockdown.
      Breast cancer cell motility was increased by expressing a constitutively-active
      RhoC(V14) mutant or overexpressing IQGAP1. EGF- or RhoC-induced migration
      required IQGAP1, but IQGAP1-stimulated migration independently of RhoC, placing
      IQGAP1 downstream of RhoC. We conclude that IQGAP1 acts both upstream of RhoA/C,
      regulating their activation state, and downstream of RhoA/C, mediating their
      effects on breast cancer cell proliferation and migration, respectively.

PMID- 22992743
TI  - The obestatin/GPR39 system is up-regulated by muscle injury and functions as an
      autocrine regenerative system.
AB  - The maintenance and repair of skeletal muscle are attributable to an elaborate
      interaction between extrinsic and intrinsic regulatory signals that regulate the
      myogenic process. In the present work, we showed that obestatin, a 23-amino acid
      peptide encoded by the ghrelin gene, and the GPR39 receptor are expressed in rat
      skeletal muscle and are up-regulated upon experimental injury. To define their
      roles in muscle regeneration, L6E9 cells were used to perform in vitro assays.
      For the in vivo assays, skeletal muscle tissue was obtained from male rats and
      maintained under continuous subcutaneous infusion of obestatin. In
      differentiating L6E9 cells, preproghrelin expression and correspondingly
      obestatin increased during myogenesis being sustained throughout terminal
      differentiation. Autocrine action was demonstrated by neutralization of the
      endogenous obestatin secreted by differentiating L6E9 cells using a specific anti
      obestatin antibody. Knockdown experiments by preproghrelin siRNA confirmed the
      contribution of obestatin to the myogenic program. Furthermore, GPR39 siRNA
      reduced obestatin action and myogenic differentiation. Exogenous obestatin
      stimulation was also shown to regulate myoblast migration and proliferation.
      Furthermore, the addition of obestatin to the differentiation medium increased
      myogenic differentiation of L6E9 cells. The relevance of the actions of obestatin
      was confirmed in vivo by the up-regulation of Pax-7, MyoD, Myf5, Myf6, myogenin,
      and myosin heavy chain (MHC) in obestatin-infused rats when compared with saline
      infused rats. These data elucidate a novel mechanism whereby the obestatin/GPR39
      system is coordinately regulated as part of the myogenic program and operates as
      an autocrine signal regulating skeletal myogenesis.

PMID- 22992744
TI  - Dynamic exchange of myosin VI on endocytic structures.
AB  - The actin-based molecular motor myosin VI functions in the endocytic uptake
      pathway, both during the early stages of clathrin-mediated uptake and in later
      transport to/from early endosomes. This study uses fluorescence recovery after
      photobleaching (FRAP) to examine the turnover rate of myosin VI during
      endocytosis. The results demonstrate that myosin VI turns over dynamically on
      endocytic structures with a characteristic half-life common to both the large
      insert isoform of myosin VI on clathrin-coated structures and the no-insert
      isoform on early endosomes. This half-life is shared by the myosin VI-binding
      partner Dab2 and is identical for full-length myosin VI and the cargo-binding
      tail region. The 4-fold slower half-life of an artificially dimerized construct
      of myosin VI on clathrin-coated structures suggests that wild type myosin VI does
      not function as a stable dimer, but either as a monomer or in a monomer/dimer
      equilibrium. Taken together, these FRAP results offer insight into both the basic
      turnover dynamics and the monomer/dimer nature of myosin VI.

PMID- 22992745
TI  - Molecular plasticity regulates oligomerization and cytotoxicity of the
      multipeptide-length amyloid-beta peptide pool.
AB  - Current therapeutic approaches under development for Alzheimer disease, including
      gamma-secretase modulating therapy, aim at increasing the production of Abeta(1
      38) and Abeta(1-40) at the cost of longer Abeta peptides. Here, we consider the
      aggregation of Abeta(1-38) and Abeta(1-43) in addition to Abeta(1-40) and Abeta(1
      42), in particular their behavior in mixtures representing the complex in vivo
      Abeta pool. We demonstrate that Abeta(1-38) and Abeta(1-43) aggregate similar to
      Abeta(1-40) and Abeta(1-42), respectively, but display a variation in the
      kinetics of assembly and toxicity due to differences in short timescale
      conformational plasticity. In biologically relevant mixtures of Abeta, Abeta(1
      38) and Abeta(1-43) significantly affect the behaviors of Abeta(1-40) and Abeta(1
      42). The short timescale conformational flexibility of Abeta(1-38) is suggested
      to be responsible for enhancing toxicity of Abeta(1-40) while exerting a cyto
      protective effect on Abeta(1-42). Our results indicate that the complex in vivo
      Abeta peptide array and variations thereof is critical in Alzheimer disease,
      which can influence the selection of current and new therapeutic strategies.

PMID- 22992746
TI  - The selenocysteine-specific elongation factor contains a novel and multi
      functional domain.
AB  - The selenocysteine (Sec)-specific eukaryotic elongation factor (eEFSec) delivers
      the aminoacylated selenocysteine-tRNA (Sec-tRNA(Sec)) to the ribosome and
      suppresses UGA codons that are upstream of Sec insertion sequence (SECIS)
      elements bound by SECIS-binding protein 2 (SBP2). Multiple studies have
      highlighted the importance of SBP2 forming a complex with the SECIS element, but
      it is not clear how this regulates eEFSec during Sec incorporation. Compared with
      the canonical elongation factor eEF1A, eEFSec has a unique C-terminal extension
      called Domain IV. To understand the role of Domain IV in Sec incorporation, we
      examined a series of mutant proteins for all of the known molecular functions for
      eEFSec: GTP hydrolysis, Sec-tRNA(Sec) binding, and SBP2/SECIS binding. In
      addition, wild-type and mutant versions of eEFSec were analyzed for Sec
      incorporation activity in a novel eEFSec-dependent translation extract. We have
      found that Domain IV is essential for both tRNA and SBP2 binding as well as
      regulating GTPase activity. We propose a model where the SBP2/SECIS complex
      activates eEFSec by directing functional interactions between Domain IV and the
      ribosome to promote Sec-tRNA(Sec) binding and accommodation into the ribosomal A
      site.

PMID- 22992747
TI  - Expansion of protein farnesyltransferase specificity using "tunable" active site
      interactions: development of bioengineered prenylation pathways.
AB  - Post-translational modifications play essential roles in regulating protein
      structure and function. Protein farnesyltransferase (FTase) catalyzes the
      biologically relevant lipidation of up to several hundred cellular proteins. Site
      directed mutagenesis of FTase coupled with peptide selectivity measurements
      demonstrates that molecular recognition is determined by a combination of
      multiple interactions. Targeted randomization of these interactions yields FTase
      variants with altered and, in some cases, bio-orthogonal selectivity. We
      demonstrate that FTase specificity can be "tuned" using a small number of active
      site contacts that play essential roles in discriminating against non-substrates
      in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase
      variants enabling the creation of bioengineered parallel prenylation pathways
      with altered substrate selectivity within a cell. Engineered FTase variants
      provide a novel avenue for probing both the selectivity of prenylation pathway
      enzymes and the effects of prenylation pathway modifications on the cellular
      function of a protein.

PMID- 22992748
TI  - A role for transcription factor STAT3 signaling in oncogene smoothened-driven
      carcinogenesis.
AB  - Activation of the Hedgehog (Hh) pathway is known to drive development of basal
      cell carcinoma and medulloblastomas and to associate with many other types of
      cancer, but the exact molecular mechanisms underlying the carcinogenesis process
      remain elusive. We discovered that skin tumors derived from epidermal expression
      of oncogenic Smo, SmoM2, have elevated levels of IL-11, IL-11Ralpha, and STAT3
      phosphorylation at Tyr(705). The relevance of our data to human conditions was
      reflected by the fact that all human basal cell carcinomas examined have
      detectable STAT3 phosphorylation, mostly in keratinocytes. The functional
      relevance of STAT3 in Smo-mediated carcinogenesis was revealed by epidermal
      specific knockout of STAT3. We showed that removal of STAT3 from mouse epidermis
      dramatically reduced SmoM2-mediated cell proliferation, leading to a significant
      decrease in epidermal thickness and tumor development. We also observed a
      significant reduction of epidermal stem/progenitor cell population and cyclin D1
      expression in mice with epidermis-specific knockout of STAT3. Our evidence
      indicates that STAT3 signaling activation may be mediated by the IL-11/IL
      11Ralpha signaling axis. We showed that tumor development was reduced after
      induced expression of SmoM2 in IL-11Ralpha null mice. Similarly, neutralizing
      antibodies for IL-11 reduced the tumor size. In two Hh-responsive cell lines,
      ES14 and C3H10T1/2, we found that addition of Smo agonist purmorphamine is
      sufficient to induce STAT3 phosphorylation at Tyr(705), but this effect was
      abolished after IL-11Ralpha down-regulation by shRNAs. Taken together, our
      results support an important role of the IL-11Ralpha/STAT3 signaling axis for Hh
      signaling-mediated signaling and carcinogenesis.

PMID- 22992749
TI  - The oxidation-sensing regulator (MosR) is a new redox-dependent transcription
      factor in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis thrives in oxidative environments such as the
      macrophage. To survive, the bacterium must sense and adapt to the oxidative
      conditions. Several antioxidant defenses including a thick cell wall, millimolar
      concentrations of small molecule thiols, and protective enzymes are known to help
      the bacterium withstand the oxidative stress. However, oxidation-sensing
      regulators that control these defenses have remained elusive. In this study, we
      report a new oxidation-sensing regulator, Rv1049 or MosR (M. tuberculosis
      oxidation-sensing regulator). MosR is a transcriptional repressor of the MarR
      family, which, similarly to Bacillus subtilis OhrR and Staphylococcus aureus
      MgrA, dissociates from DNA in the presence of oxidants, enabling transcription.
      MosR senses oxidation through a pair of cysteines near the N terminus (Cys-10 and
      Cys-12) that upon oxidation forms a disulfide bond. Disulfide formation
      rearranges a network of hydrogen bonds, which leads to a large conformational
      change of the protein and dissociation from DNA. MosR has been shown previously
      to play an important role in survival of the bacterium in the macrophage. In this
      study, we show that the main role of MosR is to up-regulate expression of rv1050
      (a putative exported oxidoreductase that has not yet been characterized) in
      response to oxidants and propose that it is through this role that MosR
      contributes to the bacterium survival in the macrophage.

PMID- 22992753
TI  - First reported case of imported human Babesia microti infection in Australia.

PMID- 22992750
TI  - Intravital microscopy: a practical guide on imaging intracellular structures in
      live animals.
AB  - Intravital microscopy is an extremely powerful tool that enables imaging several
      biological processes in live animals. Recently, the ability to image subcellular
      structures in several organs combined with the development of sophisticated
      genetic tools has made possible extending this approach to investigate several
      aspects of cell biology. Here we provide a general overview of intravital
      microscopy with the goal of highlighting its potential and challenges.
      Specifically, this review is geared toward researchers that are new to intravital
      microscopy and focuses on practical aspects of carrying out imaging in live
      animals. Here we share the know-how that comes from first-hand experience,
      including topics such as choosing the right imaging platform and modality,
      surgery and stabilization techniques, anesthesia and temperature control.
      Moreover, we highlight some of the approaches that facilitate subcellular imaging
      in live animals by providing numerous examples of imaging selected organelles and
      the actin cytoskeleton in multiple organs. 

PMID- 22992751
TI  - Tethering factor P115: a new model for tether-SNARE interactions.
AB  - The membrane tethering factor p115 has been shown to have important functions in
      ER to Golgi traffic and Golgi biogenesis. The multidomain structure of p115
      allows for interactions with a diverse array of proteins that govern cargo
      movement at the ER-Golgi interface. Within its C-terminal region p115 contains
      four coiled-coil domains (CC1-CC4). Of the four coiled-coils, only CC1 has been
      shown to be required for p115 function, presumably by its ability to bind
      numerous SNARE proteins as well as the small GTPase Rab1. Recently, we showed
      that CC4 also interacts with SNARE proteins and that CC4 is required for p115
      function in Golgi homeostasis and the trafficking of transmembrane but not
      soluble cargo. Here, we propose a novel model wherein p115 facilitates membrane
      tethering and fusion by simultaneously engaging its CC1 and CC4 domains with
      distinct SNARE proteins to promote formation of SNARE complexes. 

PMID- 22992754
TI  - A silver complex with an N,S,S-macrocyclic ligand bearing an anthracene pendant
      arm for optical ethylene monitoring.
AB  - We have synthesised a silver(I) complex with a metal-arene interaction, where the
      anthracene ring of the ligand sidearm is positioned above the silver(I) ion. The
      interaction is disrupted by ethylene coordination to the silver(I). The
      reversible interconversion between the metal-arene and metal-ethylene
      interactions allowed us to monitor the presence of ethylene.

PMID- 22992755
TI  - Investigation on psychological symptoms improves ANDROTEST accuracy in predicting
      hypogonadism in subjects with sexual dysfunction.
AB  - The role of psychological symptoms in recognizing late-onset hypogonadism (LOH)
      is still controversial. The aim of the study is to evaluate the association
      between LOH and specific psychological symptoms, and to verify whether
      investigating intra-psychic domain improves the accuracy of a validated case
      history tool (ANDROTEST) in detecting LOH. A consecutive series of 1009 subjects
      (mean age 49.23+/-13.34) consulting for sexual dysfunction was studied. Intra
      psychic symptoms were investigated by Middlesex Hospital Questionnaire (MHQ), a
      self-reported questionnaire for screening of mental disorders. A minimum set of
      two MHQ items was identified through iterative receiver-operating characteristic
      analysis, with assessment of sensitivity and specificity for hypogonadism
      (calculated free testosterone <0.225 nmol l(-1)) in an exploratory sample of 462
      patients. Sensitivity and specificity were verified in a validation sample of 547
      subjects, in which the final two-item version showed an accuracy of 58.4+/-3.2%
      in detecting hypogonadism. The combination of the two-item score with ANDROTEST
      increased the accuracy in predicting hypogonadism (0.741+/-0.029; P<0.0001) when
      compared with ANDROTEST (0.696+/-0.018; P<0.0001) and the two-item score (P<0.05)
      alone. Hence, combining these two psychological symptoms with a physical scoring
      system improves its ability in detecting hypogonadism. The combination of the
      scores should be tested in other studies.

PMID- 22992756
TI  - Cruise control for segmented flow.
AB  - Capitalizing on the benefits of microscale segmented flows, e.g., enhanced mixing
      and reduced sample dispersion, so far requires specialist training and
      accommodating a few experimental inconveniences. For instance, microscale gas
      liquid flows in many current setups take at least 10 min to stabilize and
      iterative manual adjustments are needed to achieve or maintain desired mixing or
      residence times. Here, we report a cruise control strategy that overcomes these
      limitations and allows microscale gas-liquid (bubble) and liquid-liquid (droplet)
      flow conditions to be rapidly "adjusted" and maintained. Using this strategy we
      consistently establish bubble and droplet flows with dispersed phase (plug)
      velocities of 5-300 mm s(-1), plug lengths of 0.6-5 mm and continuous phase
      (slug) lengths of 0.5-3 mm. The mixing times (1-5 s), mass transfer times (33-250
      ms) and residence times (3-300 s) can therefore be directly imposed by
      dynamically controlling the supply of the dispersed and the continuous liquids
      either from external pumps or from local pressurized reservoirs. In the latter
      case, no chip-external pumps, liquid-perfused tubes or valves are necessary while
      unwanted dead volumes are significantly reduced.

PMID- 22992757
TI  - Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast
      cancer MDA-MB-231 cells.
AB  - The activity of a peptide nucleic acid (PNA) targeting cancer-associated microRNA
      221 is described. PNAs against miR-221 were designed in order to bind very
      efficiently to the target RNA strand and to undergo efficient uptake in the
      cells. A polyarginine-PNA conjugate targeted against miR-221 (Rpep-PNA-a221)
      showed both very high affinity for RNA and efficient cellular uptake without the
      addition of transfection reagents. Unmodified PNA with the same sequence
      displayed RNA binding, but cellular uptake was very poor. Consistently, only Rpep
      PNA-a221 strongly inhibited miR-221. Targeting miR-221 by PNA resulted in i)
      lowering of the hybridization levels of miR-221 measured by RT-qPCR, ii)
      upregulation of p27Kip1 gene expression, measured by RT-qPCR and western blot
      analysis. The major conclusion of this study is that efficient delivery of anti
      miR PNA through a suitable peptide carrier (Rpep-PNA-a221) leads to inhibition of
      miR-221 activity, altering the expression of miR-221-regulated functions in
      breast cancer cells.

PMID- 22992758
TI  - Re-evaluation of the efficiency of a ceria-based thermochemical cycle for solar
      fuel generation.
AB  - A re-analysis of the ceria-based solar-thermochemical process recently presented
      by Haile, Steinfeld and coworkers (Science, 2010, 330, 1797-1801) demonstrates
      that the experimental efficiency is at least a factor of three lower than
      previously claimed. An evaluation of the theoretical efficiency points out
      fundamental limitations of the process that are based on small changes in
      stoichiometry and the requirement for large amounts of purge gas.

PMID- 22992759
TI  - sigma-Donor-sigma-acceptor plumbylene ligands: synergic sigma-donation between
      ambiphilic Pt(0) and Pb(II) fragments.
AB  - Mono- and diplatinum plumbylene complexes are prepared in which the bonding
      comprises synergic sigma donation between the Pt and Pb atoms. The bonding
      distinguishes the complexes from both the classical Fischer carbene bonding model
      and M->Pb dative-only bonding. The Pt-Pb bond of the monoplatinum complex is
      stable, while the diplatinum complex reversibly loses one Pt fragment.

PMID- 22992761
TI  - Thermal denitrogenation of 7-isopropylidene-2,3-diaza-norbornene: formation of
      substituted 3-methylene-(1,4)-pentadienes.
AB  - A theoretical study of the thermal denitrogenation of 7-isopropylidene-2,3-diaza
      norbornene is carried out by employing density functional theory and high level
      ab initio methods, such as the complete active space self-consistent field, multi
      reference second-order Moller-Plesset perturbation theory, and coupled-cluster
      singles and doubles with perturbative triples. In all computations Pople's
      polarized triple-zeta split valence basis set, 6-311G(d,p), is utilized. The
      potential energy surface for the relevant system is explored to provide a
      theoretical account for the formation of trienes (major products). For this
      purpose, a mechanism has been proposed and theoretically studied. The rate
      constant for each isomerization reaction is computed using the transition state
      theory. The simultaneous first-order ordinary-differential equations are solved
      numerically for the considered system to obtain time-dependent concentrations,
      hence the product distributions at a given temperature. Our results demonstrate
      that E- and Z-2-methyl-3-ethylidene-1,4-pentadienes are formed via a reaction
      path originating from 3-isopropylidene-1,4-pentadiene. The result of kinetic
      analysis agrees well with the experimental observations of Berson et al. (M. R.
      Mazur, S. E. Potter, A. R. Pinhas and J. A. Berson, J. Am. Chem. Soc., 1982, 104,
      6823-6824). Further, the computed percentage of trienes is in general agreement
      with experiment. Therefore, we conclude that our proposed mechanism
      satisfactorily explains the experimental observations.

PMID- 22992760
TI  - RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the
      treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) significantly affects quality of life. We recently
      cloned synoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmic
      reticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed
      in rheumatoid synovial cells and may be involved in the pathogenesis of RA.
      Inhibition of synoviolin activity is a potentially useful therapeutic approach
      for the treatment of RA. We conducted a high-throughput screen of small molecules
      to find inhibitors of synoviolin autoubiquitination activity. We identified two
      classes of small molecules, named LS-101 and LS-102, which inhibited synoviolin
      activity. LS-102 selectively inhibited synoviolin enzymatic activity, while LS
      101 inhibited a broad array of RING-type E3 ligases. Moreover, these inhibitors
      suppressed the proliferation of rheumatoid synovial cells, and significantly
      reduced the severity of disease in a mouse model of RA. Our results suggest that
      inhibition of synoviolin is a potentially useful approach in the treatment of RA.

PMID- 22992762
TI  - Early initiation of bisphosphonate does not affect healing and outcomes of volar
      plate fixation of osteoporotic distal radial fractures.
AB  - BACKGROUND: Bisphosphonates can adversely affect fracture-healing because they
      inhibit osteoclastic bone resorption. It is unclear whether bisphosphonates can
      be initiated safely for patients who have sustained an acute distal radial
      fracture. The purpose of this randomized study was to determine whether the early
      use of bisphosphonate affects healing and outcomes of osteoporotic distal radial
      fractures treated with volar locking plate fixation. METHODS: Fifty women older
      than fifty years of age who had undergone volar locking plate fixation of a
      distal radial fracture and had been diagnosed with osteoporosis were randomized
      to Group I (n = 24, initiation of bisphosphonate treatment at two weeks after the
      operation) or Group II (n = 26, initiation of bisphosphonate treatment at three
      months). Patients were assessed for radiographic union and other radiographic
      parameters (radial inclination, radial length, and volar tilt) at two, six, ten,
      sixteen, and twenty-four weeks, and for clinical outcomes that included
      Disabilities of the Arm, Shoulder and Hand (DASH) scores, wrist motion, and grip
      strength at twenty-four weeks. The two groups were compared with regard to the
      time to radiographic union, the radiographic parameters, and the clinical
      outcomes. RESULTS: No significant differences were observed between the two
      groups with respect to radiographic or clinical outcomes after volar locking
      plate fixation. All patients obtained fracture union, and the mean times to
      radiographic union in Groups I and II were similar (6.7 and 6.8 weeks,
      respectively; p = 0.65). Furthermore, the time to radiographic union was not
      related to osteoporosis severity or fracture type. CONCLUSIONS: In patients with
      an osteoporotic distal radial fracture treated with volar locking plate fixation,
      the early initiation of bisphosphonate treatment did not affect fracture-healing
      or clinical outcomes. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 22992764
TI  - hTERT-based therapy: a universal anticancer approach (Review).
AB  - Human telomerase reverse transcriptase (hTERT) has been identified as a major
      protein involved in aberrant cell proliferation, immortalization, metastasis and
      stemness maintenance in a majority of tumors, yet it has little or no expression
      in normal somatic cells. During the past few years, the development of hTERT
      based therapies such as immunotherapy, suicide gene therapy and small-molecule
      interfering therapy have become critical and specific for eradicating all types
      of cancer. Here, current knowledge regarding hTERT and its involvement in various
      cancers and its role as a target of cancer therapies are reviewed. Additionally,
      hurdles to new cancer therapy development and new therapeutic opportunities are
      described, along with areas that require further investigation.

PMID- 22992765
TI  - Stem cell transplantation in living donor renal transplantation for minimization
      of immunosuppression.
AB  - BACKGROUND: We present our experience of living-donor renal transplantation
      (LDRT) using pretransplant stem cell transplantation (SCT) where we have
      successfully achieved minimization of immunosuppression. METHODS: Nine hundred
      sixteen patients underwent LDRT between 2007 and 2011: 606 under tolerance
      induction protocol (TIP) and 310 with our usual triple immunosuppression of
      calcineurin inhibitors (CNI), mycofenolate sodium (MMF), and prednisone
      (controls). The test group (TIP) was stratified into group 1, 1 haplomatch or
      greater (n=392), group 3, less than 1 haplomatch (n=214); controls were similarly
      stratified to group 2, 1 haplomatch or greater (n=179) and group 4, less than 1
      haplomatch (n=131). The TIP consisted of donor-specific transfusion, adipose
      tissue-derived mesenchymal and hematopoietic stem cell transplantation, and
      nonmyeloablative conditioning with total lymphoid irradiation, cyclophosphamide,
      and rabbit-antithymocyte globulin. Posttransplant IS consisted of prednisone,
      CNI, or MMF, all in low doses. RESULTS: Four-year patient survival was 93.5%,
      90.7%, 88.7%, and 82.7% in groups 1 through 4, respectively, and death-censored 4
      year allograft survival was 94.8%, 95.4%, 94.5%, and 74.6%, respectively. Mean
      serum creatinine (mg/dL) for groups 1 through 4, respectively, at 4 years was
      1.26, 1.57, 1.29, and 2.1. The number of rejection episodes was highest in group
      4 and lowest in group 1. Minimization of IS was successfully achieved in 82.9%
      patients in group 1 and in 61.7% patients in group 3, whereas no minimization in
      groups 2 and 4. Stem cell transplantations were safe. CONCLUSION: Stem cell
      transplantation is effective in IS minimization in LDRT resulting in good graft
      function and patient and graft survival at 4 years.

PMID- 22992766
TI  - Role of oxygenation in hypothermic machine perfusion of kidneys from heart
      beating donors.
AB  - Dynamic preservation of organ grafts by hypothermic machine perfusion (HMP) has
      regained broader interest to provide better outcome after transplantation. One
      pivotal aspect still under debate is the role of oxygenation during HMP. The
      present study investigates functional and molecular aspects of active oxygenation
      during HMP of kidneys from heart beating donors. METHODS: Kidneys were retrieved
      from Landrace pigs (25-30 kg body weight) and preserved by pulsatile HMP for 21
      hr. All kidneys were randomly assigned to either anoxic perfusion (MPanox) or
      active oxygenation of the perfusate (MPox). All grafts were then
      autotransplanted, and the remaining native kidney was removed at the same time.
      Renal integrity and function was evaluated during perfusion and for 1 week after
      the transplantation and the removal of the remaining native kidney. RESULTS:
      Oxygenation during HMP resulted in lower endischemic vascular resistance and
      slightly elevated free radical-mediatedtissue injury during HMP. After
      reperfusion, radical mediated lipid peroxidation was twofold higher in the MPanox
      group. Renal clearance of creatinine was found significantly better during the
      first 2 days after transplantation after MPanox than after MPox. Molecular
      expression of erythropoietin was increased threefold to baseline levels after
      MPanox, indicating renal hypoxia during preservation, but was remained unchanged
      after MPox. Gene expression of sodium-glucose transporter reflected similar
      functional outcome in both groups. Fractional excretion of Na(+), proteinuria, or
      serum levels of lactate dehydrogenase were similar in both groups. CONCLUSION:
      The present data do not support the use of active oxygenation during hypothermic
      perfusion of kidneys from donors with intact circulation.

PMID- 22992767
TI  - The Seville expert workshop for progress in posttransplant lymphoproliferative
      disorders.
AB  - : Posttransplant lymphoproliferative disorders (PTLDs) are associated with
      significant morbidity and mortality among solid-organ transplant patients, but
      approaches to diagnosis and management vary considerably. An international
      multidisciplinary panel evaluated current understanding of risk factors and
      classification systems and developed recommendations to aid in PTLD prevention.
      We considered evidence on PTLD risk factors including Epstein-Barr virus
      serostatus and immunosuppression and identified knowledge gaps for future
      research. Recommendations address prophylactic and preemptive strategies to
      minimize PTLD development, including modulation of immunosuppression and
      antiviral drug regimens. Finally, new classification criteria were outlined that
      may help facilitate standardized reporting and improve our understanding of PTLD.

PMID- 22992768
TI  - Combinational effect of intestinal and hepatic CYP3A5 genotypes on tacrolimus
      pharmacokinetics in recipients of living donor liver transplantation.
AB  - BACKGROUND: For living donor liver transplantation, the genetic association of
      CYP3A5 genotype of recipient's native intestine and donor's liver allograft with
      tacrolimus pharmacokinetics has not been explained completely considering liver
      regeneration time. The goal of the study was to investigate the longitudinal
      effects of recipient-donor combinational CYP3A5 genotypes on tacrolimus dose
      normalized concentration (C/D ratio) in blood. METHODS: Tacrolimus blood
      concentrations were measured for 58 Korean adult living donor liver transplant
      recipients on tacrolimus-based immunosuppressants during 4 years of follow-up.
      CYP3A5 was genotyped for both recipient and donor, and the recipient-donor
      combinational genetic effect on tacrolimus C/D ratios were evaluated as a
      function of time after adjusting for covariates including demographics and
      clinical variables. RESULTS: CYP3A5 expresser recipients grafted from CYP3A5
      expresser donors consistently had the least C/D ratio throughout the entire study
      period, whereas CYP3A5 expresser recipients grafted from CYP3A5 nonexpresser
      donors had an intermediate, and CYP3A5 nonexpresser recipients grafted from
      CYP3A5 nonexpresser donors had the largest C/D ratio (all P < 0.01). The CYP3A5
      nonexpresser recipients grafted from CYP3A5 expresser donors showed a significant
      decrease from the largest to the intermediate in C/D ratio for the first month.
      CONCLUSIONS: CYP3A5 genotypes of both recipient and donor were important factors
      influencing pharmacokinetic variability of tacrolimus. The recipient-donor
      combinational genetic effect on C/D ratio changed over time after
      transplantation.

PMID- 22992769
TI  - Identification of biomarkers to assess organ quality and predict
      posttransplantation outcomes.
AB  - The increased disparity between organ supply and need has led to the use of
      extended criteria donors and donation after cardiac death donors with other
      comorbidities. METHODS: We have examined the preimplantation transcriptome of 112
      kidney transplant recipient samples from 100 deceased-donor kidneys by microarray
      profiling. Subject groups were segregated based on estimated glomerular
      filtration rate (eGFR) at 1 month after transplantation: the GFR-high group
      (n=74) included patients with eGFR 45 mL/min per 1.73 m(2), whereas the GFR-low
      group (n=35) included patients with eGFR 45 mL/min or less per 1.73 m(2).
      RESULTS: Gene expression profiling identified higher expression of 160 probe sets
      (140 genes) in the GFR-low group, whereas expression of 37 probe sets (33 genes)
      was higher in the GFR-high group (P<0.01, false discovery rate <0.2). Four genes
      (CCL5, CXCR4, ITGB2, and EGF) were selected based on fold change and P value and
      further validated using an independent set of samples. A random forest analysis
      identified three of these genes (CCL5, CXCR4, and ITGB2) as important predictors
      of graft function after transplantation. CONCLUSIONS: Inclusion of
      pretransplantation molecular gene expression profiles in donor quality assessment
      systems may provide the necessary information for better donor organ selection
      and function prediction. These biomarkers would further allow a more objective
      and complete assessment of procured renal allografts at pretransplantation time.

PMID- 22992770
TI  - An effective immune-monitoring protocol based on gene expression profiles in the
      peripheral T-cell fraction reactive to graft antigens.
AB  - BACKGROUND: The ability to induce tolerance, or at least minimize the need for
      immunosuppressive therapy, is a high priority in organ transplantation.
      Accomplishing this goal requires a novel method for determining when a patient
      has become tolerant to or is rejecting their graft. Here, we sought to develop an
      efficient monitoring protocol based on gene expression profiles of recipient T
      cells in murine skin and islet allograft models. METHODS: Unlike previous
      studies, here, gene expression analysis was focused on donor antigen-reactive T
      cells, which were prepared by collecting CD69(+) T cells from cocultures of
      recipient peripheral T cells and donor antigen-presenting cells. Candidate
      tolerance and rejection biomarker genes were selected from a CD69(+) T-cell
      microarray analysis, and their expression levels were measured in the recipient
      CD69(+) T-cell fraction using quantitative reverse transcription polymerase chain
      reaction. RESULTS: Our new monitoring protocol was capable of precisely detecting
      the immune status of recipients relative to their graft regardless of the organ
      received, whether they were taking immunosuppressive drugs, or different strains
      of origin. CONCLUSIONS: Gene expression analysis focusing on recipient CD69(+) T
      cells as the donor antigen-reactive T-cell population could be used as an
      effective and sensitive method for monitoring transplant patients.

PMID- 22992771
TI  - Nickel-catalyzed alpha-glycosylation of C(1)-hydroxyl D-myo-inositol: a formal
      synthesis of mycothiol.
AB  - Formal synthesis of mycothiol has been developed via nickel-catalyzed alpha
      glycosylation of the C(1)-hydroxyl group of D-myo-inositols with C(2)-N
      substituted benzylideneamino N-phenyl trifluoroacetimidate donors. The pseudo
      oligosaccharides were obtained in good yield and with excellent alpha
      selectivity. Removal of the C(2)-N-2-trifluoromethylphenyl-benzylidene group
      under mild conditions provides a pseudo-disaccharide, completing the formal
      synthesis of mycothiol.

PMID- 22992774
TI  - Pentanucleotide repeat-primed PCR for genetic diagnosis of spinocerebellar ataxia
      type 31.
AB  - Spinocerebellar ataxia type 31 (SCA31) is defined by the presence of an insertion
      mutation containing a TGGAA repeat within the intron of the brain-expressed,
      associated with NEDD4 (BEAN) gene. Detecting this mutation is conventionally done
      by southern blotting or DNA sequencing, but these methods are technically
      demanding and not easily implemented in clinical diagnosis. Here, we adapted
      repeat-primed PCR (RP-PCR) to develop a clinical genetic test for SCA31 using
      only the PCR process to detect the TGGAA repeat within the insertion mutation.
      Pentanucleotide RP-PCR and subsequent DNA fragment analysis demonstrated
      characteristic ladder peaks with a 5-bp periodicity, originating from the TGGAA
      repeat, in 100% of samples (n=14) from SCA31 patients in whom the presence of the
      TGGAA repeat had been verified by DNA sequencing. No peaks were observed in a
      normal control and two non-SCA31 patients, in whom the TGGAA repeat was absent.
      This method is valuable for genetic diagnosis of SCA31 in clinical practice.

PMID- 22992773
TI  - The autophagy-related gene 14 (Atg14) is regulated by forkhead box O
      transcription factors and circadian rhythms and plays a critical role in hepatic
      autophagy and lipid metabolism.
AB  - Autophagy plays a critical role in cell survival from prolonged starvation and
      recycling of aggregated proteins and damaged organelles. One of the essential
      genes involved in the autophagic initiation is autophagy-related 14 (Atg14), also
      called Barkor for Beclin 1-associated autophagy-related key regulator. Although
      its crucial role in the autophagic process has been reported, the gene regulation
      of Atg14 and its metabolic functions remain unclear. In this work we have
      identified that the Atg14 gene is regulated by forkhead box O (FoxO)
      transcription factors and circadian rhythms in the mouse liver. Luciferase
      reporter analyses and chromatin immunoprecipitation assays have revealed well
      conserved cis-elements for FoxOs and Clock/Bmal1 in the proximal promoter of the
      Atg14 gene. To examine the functions of hepatic Atg14, we have performed the gene
      knockdown and overexpression in the mouse livers. Remarkably, knockdown of Atg14
      leads to elevated levels of triglycerides in the liver and serum as well.
      Conversely, overexpression of Atg14 improves hypertriglyceridemia in both high
      fat diet-treated wild-type mice and FoxO1/3/4 liver-specific knock-out mice. In
      summary, our data suggest that Atg14 is a new target gene of FoxOs and the core
      clock machinery, and this gene plays an important role in hepatic lipid
      metabolism.

PMID- 22992775
TI  - Is the prevalence of MTHFR C677T polymorphism associated with ultraviolet
      radiation in Eurasia?
AB  - The methylenetetrahydrofolic acid reductase (MTHFR) C677T polymorphism causes an
      amino-acid change from alanine to valine and results in the enzyme becoming
      thermolabile and half decreased activity. Its prevalence varies among global
      population. We collected data about MTHFR C677T polymorphism prevalence from
      epidemiology studies, as well as ultraviolet (UV) radiations and some other
      climatological factors from the internet. The results of the correlation and
      quadric regression showed that there was inverse U-shape relationship between T
      allele frequency and UV radiation. The explanatory power of UV radiation was
      stronger than latitude and all climatological factors. Our results supported the
      hypothesis that the distribution pattern of MTFHR C677T polymorphism in Eurasia
      might be the result of interaction of genetic and environmental natural
      selection, especially the UV radiation.

PMID- 22992776
TI  - Variations with modest effects have an important role in the genetic background
      of type 2 diabetes and diabetes-related traits.
AB  - The aim of the present study was to explore the role of variations with modest
      effects (previously identified by a large-scale meta-analysis in European
      populations) in the genetic background of type 2 diabetes (T2D) and diabetes
      related traits in a Japanese population. We enrolled 2632 Japanese subjects with
      T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide
      polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349
      (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1),
      rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and
      rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and
      P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to
      nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting
      plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA
      beta (P=0.033) compared with subjects who had fewer risk alleles. We identified a
      significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a
      Japanese population. The present findings suggest that inclusion of SNPs with a
      tendency to increase the disease risk captured more of the genetic background of
      T2D than that revealed by only assessing significant SNPs.

PMID- 22992777
TI  - Detection of significant pathways in osteoporosis based on graph clustering.
AB  - Osteoporosis is the most common and serious skeletal disorder among the elderly,
      characterized by a low bone mineral density (BMD). Low bone mass in the elderly
      is highly dependent on their peak bone mass (PBM) as young adults. Circulating
      monocytes serve as early progenitors of osteoclasts and produce significant
      molecules for bone metabolism. An improved understanding of the biology and
      genetics of osteoclast differentiation at the pathway level is likely to be
      beneficial for the development of novel targeted approaches for osteoporosis. The
      objective of this study was to explore gene expression profiles comprehensively
      by grouping individual differentially expressed genes (DEGs) into gene sets and
      pathways using the graph clustering approach and Gene Ontology (GO) term
      enrichment analysis. The results indicated that the DEGs between high and low PBM
      samples were grouped into nine gene sets. The genes in clusters 1 and 8
      (including GBP1, STAT1, CXCL10 and EIF2AK2) may be associated with osteoclast
      differentiation by the immune system response. The genes in clusters 2, 7 and 9
      (including SOCS3, SOD2, ATF3, ADM EGR2 and BCL2A1) may be associated with
      osteoclast differentiation by responses to various stimuli. This study provides a
      number of candidate genes that warrant further investigation, including DDX60,
      HERC5, RSAD2, SIGLEC1, CMPK2, MX1, SEPING1, EPSTI1, C9orf72, PHLDA2, PFKFB3,
      PLEKHG2, ANKRD28, IL1RN and RNF19B.

PMID- 22992778
TI  - Highly sensitive and selective chemiresistive sensors based on multidimensional
      polypyrrole nanotubes.
AB  - Multidimensional polypyrrole nanotubes (MPPy NTs) were successfully fabricated as
      chemiresistors on a sacrificial nanofiber template by vapor deposition
      polymerization (VDP) and used to discriminate volatile organic compounds (VOCs)
      and toxic gases.

PMID- 22992779
TI  - Prevalence and determinants of electrocardiographic abnormalities in sub-Saharan
      African individuals with type 2 diabetes.
AB  - AIM: This study assessed the prevalence and determinants of electrocardiographic
      abnormalities in a group of type 2 diabetes patients recruited from two referral
      centres in Cameroon. METHODS: A total of 420 patients (49% men) receiving chronic
      diabetes care at the Douala General and Yaounde Central hospitals were included.
      Electrocardiographic abnormalities were investigated, identified and related to
      potential determinants, with logistic regressions. RESULTS: The mean age and
      median duration of diagnosis were 56.7 years and four years, respectively. The
      main electrocardiographic aberrations (prevalence %) were: T-wave abnormalities
      (20.9%), Cornell product left ventricular hypertrophy (16.4%), arrhythmia
      (16.2%), ischaemic heart disease (13.6%), conduction defects (11.9%), QTc
      prolongation (10.2%) and ectopic beats (4.8%). Blood pressure variables were
      consistently associated with all electrocardiographic abnormalities. Diabetes
      specific factors were associated with some abnormalities only. CONCLUSIONS:
      Electrocardiographic aberrations in this population were dominated by
      repolarisation, conduction defects and left ventricular hypertrophy, and were
      more related to blood pressure than diabetes-specific factors.

PMID- 22992781
TI  - Bisphosphonates are safe after ORIF for distal radial fractures: commentary on an
      article by Hyun Sik Gong, MD, PhD, et al.: "early initiation of bisphosphonate
      does not affect healing and outcomes of volar plate fixation of osteoporotic
      distal radial fractures".

PMID- 22992780
TI  - Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis
      associated behavior in gastric cancer.
AB  - Aberrant glycosylation of cell surface glycoprotein due to specific alterations
      of glycosyltransferase activity is usually associated with invasion and
      metastasis of cancer, particularly of gastric carcinomas. Polypeptide N
      acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of
      mucin-type O-glycosylation, is also involved in tumor migration and invasion.
      However, a comprehensive understanding of how ppGalNAc-T2 correlates with the
      metastasic potential of human gastric cancer is not currently available. In the
      present study, ppGalNAc-T2 was detected in a variety of human poorly
      differentiated tumor cells, and expression appeared to be higher in SGC7901
      gastric cancer cells. In addition, we investigated the potential effects of
      ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after
      stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that
      cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2
      overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore,
      we attempted to clarify the mechanisms underlying the anti-metastatic activities
      of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc
      T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression
      at both the protein and mRNA levels, which may be associated with ppGalNAc-T2
      suppressing the expression of transforming growth factor (TGF)-beta1. However, it
      did not exhibit any apparent correlation with MMP-14 expression levels. Our data
      show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901
      gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative
      and anti-metastatic activity through the decrease of MMP-2 and TGF-beta1. These
      results indicate that ppGalNAc-T2 may be used as a novel therapeutic target for
      human gastric cancer treatment.

PMID- 22992783
TI  - Observation of a ferric hydroperoxide complex during the non-heme iron catalysed
      oxidation of alkenes and alkanes by O2.
AB  - A non-heme iron complex catalyses the oxidation of allylic, benzylic, and
      aliphatic C-H bonds by O(2). During this reactivity, a ferric hydroperoxide
      species is observed. The kinetic analysis of this complex's formation may suggest
      a ferric superoxo species as the initial metal-based oxidant.

PMID- 22992784
TI  - Chemical composition of hexane extract of Citrus aurantifolia and anti
      Mycobacterium tuberculosis activity of some of its constituents.
AB  - The main aim of this study was to isolate and characterize the active compounds
      from the hexane extract of the fruit peels of Citrus aurantiifolia, which showed
      activity against one sensitive and three monoresistant (isoniazid, streptomycin
      or ethambutol) strains of Mycobacterium tuberculosis H37Rv. The active extract
      was fractionated by column chromatography, yielding the following major
      compounds: 5-geranyloxypsoralen (1); 5-geranyloxy-7-methoxycoumarin (2); 5,7
      dimethoxycoumarin (3); 5-methoxypsoralen (4); and 5,8-dimethoxypsoralen (5). The
      structures of these compounds were elucidated by 1D and 2D NMR spectroscopy. In
      addition, GC-MS analysis of the hexane extract allowed the identification of 44
      volatile compounds, being 5,7-dimethoxycoumarin (15.79%), 3-methyl-1,2
      cyclopentanedione (8.27%), 1-methoxy-ciclohexene (8.0%), corylone (6.93%),
      palmitic acid (6.89%), 5,8-dimethoxypsoralen (6.08%), a-terpineol (5.97%), and
      umbelliferone (4.36%), the major constituents. Four isolated coumarins and 16
      commercial compounds identified by GC-MS were tested against M. tuberculosis
      H37Rv and three multidrug-resistant M. tuberculosis strains using the Microplate
      Alamar Blue Assay. The constituents that showed activity against all strains were
      5 (MICs = 25-50 mg/mL), 1 (MICs = 50-100 mg/mL), palmitic acid (MICs = 25-50
      mg/mL), linoleic acid (MICs = 50-100 mg/mL), oleic acid (MICs = 100 mg/mL), 4
      hexen-3-one (MICs = 50-100 mg/mL), and citral (MICs = 50-100 mg/mL). Compound 5
      and palmitic acid were the most active ones. The antimycobacterial activity of
      the hexane extract of C. aurantifolia could be attributed to these compounds.

PMID- 22992785
TI  - In vitro antioxidant activity potential of lantadene A, a pentacyclic
      triterpenoid of Lantana plants.
AB  - Lantadenes are pentacyclic triterpenoids present in the leaves of the plant
      Lantana camara. In the present study, in vitro antioxidant activity and free
      radical scavenging capacity of lantadene A was evaluated using established in
      vitro models such as ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1
      picryl-hydrazyl (DPPH*), hydroxyl radical (OH*), nitric oxide radical (NO*),
      superoxide anion scavenging activities and ferrous ion chelating assay.
      Interestingly, lantadene A showed considerable in vitro antioxidant, free radical
      scavenging capacity activities in a dose dependant manner when compared with the
      standard antioxidant in nitric oxide scavenging, superoxide anion radical
      scavenging and ferrous ion chelating assay. These findings show that the
      lantadene A possesses antioxidant activity with different mechanism of actions
      towards the different free radicals tested. Since lantadene A is a very popular
      drug in modern medicine, it is a promising candidate for use as an antioxidant
      and hepatoprotective agent.

PMID- 22992786
TI  - Microfluidic one-step fabrication of radiopaque alginate microgels with in situ
      synthesized barium sulfate nanoparticles.
AB  - In this work, we report a new strategy to fabricate monodispersed radiopaque
      alginate (Ba-alginate) microgels by a one-step microfluidic method. Alginate
      droplets containing sulfate ions are first formed by a flow focusing microfluidic
      setup. These alginate droplets are subsequently solidified by barium ions in a
      collection bath. During the solidification process, excessive barium ions in the
      collection bath also react with sulfate ions in the alginate droplet, resulting
      in barium sulfate (BaSO(4)) nanoparticles in situ synthesized (acting as
      radiopaque imaging agents) within the Ba-alginate microgels. Scanning electron
      microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX)
      illustrate that 800 nm BaSO(4) nanoparticles are uniformly distributed inside the
      30 MUm Ba-alginate microgels, with 62 wt% of elemental barium (Ba). In addition,
      X-ray diffraction (XRD) measurements indicate that the BaSO(4) nanoparticles
      consist of 10 nm in situ synthesized BaSO(4) crystallites. The alginate microgels
      act as a soft and porous template to prevent the precipitation and aggregation of
      BaSO(4) nanoparticles. The Ba-alginate microgels are also visible under X-ray
      radiation. The facile route to fabricate alginate microgels as radiopaque embolic
      materials is of particular importance for endovascular embolization and localized
      diagnostic imaging applications. Similar approaches can also be adopted for
      synthesizing other inorganic nanoparticles in microgels.

PMID- 22992787
TI  - LOH 19q indicates shorter disease progression-free interval in low-grade
      oligodendrogliomas with EMP3 methylation.
AB  - We previously described a cohort of grade II oligodendroglioma (OII) patients, in
      whom the loss of heterozygosity (LOH) 19q was present in the subgroup at a higher
      risk of relapse. In this study, we evaluated the CpG methylation of the putative
      tumor suppressor epithelial membrane protein 3 (EMP3, 19q13.3) gene promoter in
      the same OII cohort, to investigate whether a correlation could be found between
      EMP3 cytogenetic and epigenetic loss and higher risk of relapse. Twenty-three
      tumor samples from OII patients were collected over a period of 10 years.
      Seventeen glioblastoma (GBM) samples (2 of which were relapses) were collected
      from 15 patients. The EMP3, O6-methylguanine methyltransferase (MGMT) and
      cyclooxygenase 2 (COX2) promoter methylation, evaluated by methylation-specific
      PCR, and the isocitrate dehydrogenase 1 (IDH1) mutation, identified by
      sequencing, were compared between the OII and GBM histotypes. The EMP3 promoter
      methylation was correlated with the analysis of LOH 19q, performed by
      microsatellite amplification, in OII patients. Disease progression-free interval
      was evaluated in the OII patients with the EMP3 methylation with either LOH 19q
      or conserved chromosome 19 arms. The EMP3 and MGMT promoter methylation was more
      frequent in OII than in GBM patients, and the IDH1 mutation was absent in GBM.
      The COX2 promoter was unmethylated in both histotypes. Both LOH+/- 19q OII
      patients showed EMP3 hypermethylation. Concomitant LOH 19q and EMP3 gene promoter
      methylation was observed in the OII patients at a higher risk of relapse. Our
      results suggest that a total (cytogenetic and epigenetic) functional loss of both
      EMP3 alleles accounts for the reduced disease progression-free interval in OII
      patients. Although the small sample size limits the strength of this study, our
      results support testing this hypothesis in larger cohorts of patients,
      considering the methylation of the EMP3 gene promoter together with LOH 19q as an
      indication for treatment with adjuvant therapy ab initio in order to improve the
      overall survival of OII patients.

PMID- 22992788
TI  - Support vector machines coupled with proteomics approaches for detecting
      biomarkers predicting chemotherapy resistance in small cell lung cancer.
AB  - The aim of this study was to identify serum protein fingerprints of small cell
      lung cancer (SCLC) and potential biomarkers related to chemotherapy resistance of
      SCLC with surface enhanced laser desorption/ionization time of flight mass
      spectrometry (SELDI-TOF MS). A total of 60 SCLC patients and 48 age- and sex
      matched healthy individuals were enrolled. The chemotherapy regimen was cisplatin
      plus etoposide. All patients received two cycles of chemotherapy. Serum protein
      profiles were detected using SELDI-TOF MS and the spectra were analyzed with
      support vector machines (SVMs). Western blotting was performed to verify the
      results of SELDI-TOF MS. Three top scored peaks, at m/z of 6269, 9043 and 13124
      Da, were finally selected as potential biomarkers for detection of SCLC. The SVM
      classifier separated the SCLC from the healthy samples in the blind test, with a
      sensitivity of 92.4% and a specificity of 92.5%. For the 56 eligible chemotherapy
      patients, 4 had a complete response (7.14%), 39 patients had a partial response
      (69.6%), 9 patients had a stable disease (16.1%) and 4 patients had a progressive
      disease (7.14%). The model constructed using two protein peaks with m/z of 8830
      and 10468 Da separated the chemotherapy-resistant group from the chemotherapy
      sensitive group with a sensitivity of 80.0% and a specificity of 80.0%. Initial
      protein database searching identified 10468 Da as S100-A9 which was confirmed by
      western blotting. The present results suggest that the combination of SELDI-TOF
      MS with SVM may provide a useful means in the search for serum biomarkers for
      predicting chemotherapy resistance in patients with SCLC.

PMID- 22992790
TI  - Immunogenicity of Cpn0425 and its localization in cells infected with
      Chlamydophila pneumoniae.
AB  - The present study aimed to determine the intracellular localization of Cpn0425 in
      Chlamydophila pneumoniae-infected cells. The recombinant plasmid pGEX-6p/Cpn0425
      was transformed into E.coli Bl21 cells to express the fusion protein. Following
      purification with glutathione S-transferase (GST) resin chromatography, the
      Cpn0425 fusion protein was used to induce immunity in mice to develop monoclonal
      and polyclonal antibodies, which were subsequently used to localize the
      endogenous Cpn0425 protein by indirect immunofluorescence assay (IFA). ELISA was
      used to determine the immunogenicity of the Cpn0425 plasmid protein by
      recognizing the pool sera of patients infected with Chlamydia trachomatis and the
      pool sera of mice immunized with the Cpn0425 fusion protein. The Cpn0425 gene was
      expressed as the GST-Cpn0425 fusion protein in E. coli and its antibody was
      prepared by immunizing mice with the fusion protein. An anti-GST-Cpn0425 antibody
      was used to localize the protein in cells infected with Chlamydophila pneumoniae
      AR-39 using an IFA. The anti-GST-CT058 antibody detected an inclusion signal in
      the IFA. Cpn0425 protein strongly reacted with antiserum. Although Cpn0425
      protein is not a secreted protein, it has good immunogenicity. Therefore, this
      protein may be useful for developing vaccines against Chlamydophila pneumoniae
      infection.

PMID- 22992791
TI  - Direct benzylic metalation of a phenethylamine derivative: potassium as the key
      to both generation and stabilization of a labile anion.
AB  - t-BuLi-t-BuOK selectively metalates the benzylic position of 2
      phenylethyldimethylamine under mild conditions without occurrence of beta
      elimination in the resulting metalated species. Theoretical and structural
      studies indicate that potassium is crucial for both the lowering of the barrier
      of the initial deprotonation step and the stabilization of the labile anion.

PMID- 22992792
TI  - Cl-OH ion-exchanging process in chlorapatite (Ca5(PO4)3Cl(x)(OH)(1-x))--a deep
      insight.
AB  - We have synthesized large chlorapatite [ClAp, Ca(5)(PO(4))(3)Cl(x)(OH)(1-x),
      where x = 1] single crystals using the molten salt method. We have corroborated
      that the hexagonal symmetry P6(3)/m describes the crystal structure best, even
      though the crystals are synthetic and stoichiometric. Moreover, we have performed
      several thermal treatments on these ClAp crystals, generating new single crystals
      in the apatite system [Ca(5)(PO(4))(3)Cl(x)(OH)(1-x), where x <= 1], where the
      chloride anions (Cl(-)) were systematically substituted by hydroxyl anions (OH(
      )). These new single crystals were methodically characterized by powder and
      single-crystal X-ray diffraction (SXRD), scanning electron microscopy (SEM),
      Fourier transform-IR spectroscopy (FT-IR), and energy-dispersive X-ray
      spectroscopy (EDS). We have discovered a previously unreported OH(-) inclusion
      site substituting the Cl(-) anion during the ion-exchanging process. Finally, we
      evaluated the atomic rearrangements of the other species involved in the
      structure. These movements are associated with ionic exchange, which can be
      justified from an energetic point of view. We also found a novel phase
      transformation at high temperature. When the crystals are heated over 1753 K the
      apatite system evolves to a less ordered monoclinic structure, in which the
      complete loss of the species in the anionic channel (Cl(-), OH(-)) has been
      confirmed.

PMID- 22992793
TI  - Comparative modular analysis of two complex sulfosalt structures: sterryite,
      Cu(Ag,Cu)3Pb19(Sb,As)22(As-As)S56, and parasterryite, Ag4Pb20(Sb,As)24S58.
AB  - The crystal structures of two very close, but distinct complex minerals of the
      lead sulfosalt group have been solved: sterryite,
      Cu(Ag,Cu)(3)Pb(19)(Sb,As)(22)(As-As)S(56), and parasterryite,
      Ag(4)Pb(20)(Sb,As)(24)S(58). They are analyzed and compared according to modular
      analysis. The fundamental building block is a complex column centred on a
      Pb(6)S(12) triangular prismatic core, with two additional long and short arms.
      The main chemical and topological differences relate to the short arm, which
      induces a relative a/4 shift (~2 A along the elongation parameter) of the
      constitutive rod layers, as illustrated by distinct cell settings within the same
      space group (P2(1)/n and P2(1)/c, respectively). Selection of the shortest (i.e.
      strongest) (Sb,As)-S bonds permitted to enhance the polymeric organization of
      (Sb,As) atoms with triangular pyramidal coordination. These two quasi-homeotypic
      structures are expanded derivatives of owyheeite, Ag(3)Pb(10)Sb(11)S(28). The
      hierarchy of organization levels from zero- to three-dimensional entities is
      subordinated to building operators, which appear as the driving force for the
      construction of such complex structures. Minor cations (Ag, Cu) or the As-As pair
      in sterryite secure the final locking, which favours the formation of one or the
      other compound.

PMID- 22992794
TI  - Crystal structures of calcium hemicarboaluminate and carbonated calcium
      hemicarboaluminate from synchrotron powder diffraction data.
AB  - One of the main phases formed at the beginning of the carbonation reaction of
      cementitious building materials is the calcium hemicarboaluminate (abbreviated as
      Hc). This AFm (shorthand for hydrated calcium aluminate phases structurally
      related to hydrocalumite) phase was synthesized, crystallized and then studied by
      synchrotron X-ray powder diffraction and micro-Raman spectroscopy. At room
      temperature and standard experimental conditions two major cementitious phases
      were detected, the Hc phase (as a major phase) and carbonated calcium
      hemicarboaluminate (abbreviated as cHc). By increasing the temperature the Hc
      form transforms into cHc. The crystal structures of these important AFm phases
      were successfully solved and refined in the R3c space group of the trigonal
      crystal system. Hc has the unit-cell parameters a = 5.7757 (1) and c = 48.812 (2)
      A, and cHc the unit-cell parameters a = 5.7534 (1) and c = 46.389 (1) A. The two
      crystal structures are composed of positively charged main layers,
      [Ca(4)Al(2)(OH)(12)](2+), and negatively charged interlayers, [OH(2n)(CO(3))(1 -
      n).4H(2)O](2-). The structure of the main layers is typical of the AFm family.
      Conversely, the interlayer region has a characteristic structure built up from
      water molecules and statistically distributed anions. In the interlayer, the Hc
      carbonate and hydroxyl anions are distributed in a 0.25:0.5 ratio, whereas the
      ratio of the anions in the cHc interlayers is 0.4:0.2.

PMID- 22992795
TI  - Theoretical hardness calculated from crystallo-chemical data for MoS2 and WS2
      crystals and nanostructures.
AB  - The calculation of the hardness of Mo and W disulfides using a crystallo-chemical
      model provides a unique opportunity to obtain separate quantitative information
      on the maximum hardness H(max) governed by strong intra-layer covalent bonds
      acting within the (0001) plane versus the minimum hardness H(min) governed by
      weak inter-layer van der Waals bonds acting along the c-axis of the hexagonal
      lattice. The penetration hardness derived from fundamental crystallo-chemical
      data (confirmed by experimental determinations) proved to be far lower in MS(2)
      (M = Mo, W) than in graphite and hexagonal BN, both for H(max) (H(graph)/H(MoS2)
      = 3.85; H(graph)/H(WS2) = 3.60; H(hBN)/H(MoS2) = 2.54; H(hBN)/H(WS2) = 2.37) as
      well as for H(min) (H(graph)/H(MoS2) = 6.22; H(graph)/H(WS2) = 5.87;
      H(hBN)/H(MoS2) = 4.72; H(hBN)/H(WS2) = 4.46). However, the gap between H(max) and
      H(min) is considerably larger in MS(2) (M = Mo,W), as indicated by H(max)/H(min)
      being 279 in 2H-MoS(2), 282 in 2H-WS(2), 173 in graphite and 150 in hBN. The gap
      was found to be even larger in MS(2) (M = Mo, W) nanostructures. These findings
      help to explain the excellent properties of MS(2) (M = Mo, W) as solid lubricants
      in high tech fields, either as bulk 2H crystals (inter-layer shear and peeling
      off lubricating mechanisms), or especially as onion-like fullerene nanoparticles
      (rolling/sliding mechanisms).

PMID- 22992796
TI  - Unique thermodynamic relationships for DeltafHo and DeltafGo for crystalline
      inorganic salts. I. Predicting the possible existence and synthesis of Na2SO2 and
      Na2SeO2.
AB  - The concept that equates oxidation and pressure has been successfully utilized in
      explaining the structural changes observed in the M(2)S subnets of M(2)SO(x) (x =
      3, 4) compounds (M = Na, K) when compared with the structures (room- and high
      pressure phases) of their parent M(2)S 'alloy' [Martinez-Cruz et al. (1994), J.
      Solid State Chem. 110, 397-398; Vegas (2000), Crystallogr. Rev. 7, 189-286; Vegas
      et al. (2002), Solid State Sci. 4, 1077-1081]. These structural changes suggest
      that if M(2)SO(2) would exist, its cation array might well have an anti-CaF(2)
      structure. On the other hand, in an analysis of the existing thermodynamic data
      for M(2)S, M(2)SO(3) and M(2)SO(4) we have identified, and report, a series of
      unique linear relationships between the known Delta(f)H(o) and Delta(f)G(o)
      values of the alkali metal (M) sulfide (x = 0) and their oxyanion salts M(2)SO(x)
      (x = 3 and 4), and the similarly between M(2)S(2) disulfide (x = 0) and disulfur
      oxyanion salts M(2)S(2)O(x) (x = 3, 4, 5, 6 and 7) and the number of O atoms in
      their anions x. These linear relationships appear to be unique to sulfur
      compounds and their inherent simplicity permits us to interpolate thermochemical
      data (Delta(f)H(o)) for as yet unprepared compounds, M(2)SO (x = 1) and M(2)SO(2)
      (x = 2). The excellent linearity indicates the reliability of the interpolated
      data. Making use of the volume-based thermodynamics, VBT [Jenkins et al. (1999),
      Inorg. Chem. 38, 3609-3620], the values of the absolute entropies were estimated
      and from them, the standard Delta(f)S(o) values, and then the Delta(f)G(o) values
      of the salts. A tentative proposal is made for the synthesis of Na(2)SO(2) which
      involves bubbling SO(2) through a solution of sodium in liquid ammonia. For this
      attractive thermodynamic route, we estimate DeltaG(o) to be approximately -500 kJ
      mol(-1). However, examination of the stability of Na(2)SO(2) raises doubts and
      Na(2)SeO(2) emerges as a more attractive target material. Its synthesis is likely
      to be easier and it is stable to disproportionation into Na(2)S and Na(2)SeO(4).
      Like Na(2)SO(2), this compound is predicted to have an anti-CaF(2) Na(2)Se
      subnet.

PMID- 22992797
TI  - Topological studies of three related metal-organic frameworks of GdIII and 5
      nitroisophthalate.
AB  - The reaction of 5-nitroisophthalic acid (H(2)NIA) with Gd(NO(3))(3).6H(2)O in DMF
      afforded three new metal-organic frameworks: [Gd(NIA)(1.5)(DMF)(2)].DMF (I),
      [Gd(2)(NIA)(3)(DMF)(4)].xH(2)O (II) and
      [Gd(4)(NIA)(6)(DMF)(5.5)(H(2)O)(3)].4DMF.H(2)O (III). These compounds can be
      prepared through a variety of methods. Compounds (I) and (II) are more
      reproducibly formed than compound (III). Network analysis revealed (I) to have a
      (4(12).6(3))-pcu topology, while (II) displays a (4(2).8(4))(4(2).8(4))-pts
      topology. Compound (III) was found to present the uncommon 4,5,6T11 topological
      net, which combines aspects of both the pcu and pts topologies. The short symbol
      of this net is (4(4).6(2))(4(6).6(4))(2)(4(8).6(6).8).

PMID- 22992798
TI  - Four polymorphs (polytypes) of 5,6-dimethylbenzofurazan 1-oxide.
AB  - 5,6-Dimethylbenzofurazan 1-oxide (Me2BF), C(8)H(8)N(2)O(2), occurs in four
      polymorphic forms that are polytypes of each other. Each polymorph of Me2BF
      contains molecules disordered about pseudo-twofold axes and arranged head-to-tail
      in ribbons, with the ribbons forming approximately planar layers held together by
      weak C-H...N and C-H...O interactions. Adjacent layers interact in different ways
      in the different polymorphs. In addition to twinning in the individual
      polymorphs, four examples of allotwining, that is, oriented overgrowths between
      different polymorphs, were found.

PMID- 22992799
TI  - Structure of twisted BNC nanotubes with polygonal cross-section.
AB  - BNC nanotubes and nanofibers have been synthesized in the high isostatic pressure
      apparatus in Ar at 1923 K and 1.5 MPa in the presence of yttrium aluminium
      garnet. Some of the nanotubes obtained were filled with Al(2)O(3). Transmission
      electron microscopy (TEM) studies have shown that the nanotubes and nanofibers
      have a polygonal cross-section (prismatic shape), and most often they are
      twisted, which is due to the transversal instability of the nanotubes originating
      under the growth conditions, including temperature treatment. Twisting also
      revealed itself in the appearance of the moire fringes during the TEM observation
      of some of the nanotubes and nanofibers. Analysis of these fringes has shown that
      the facets of these nanotubes represent the slightly misoriented hexagonal BN
      and/or C plates. An Al(2)O(3) filling of the nanotube makes it harder to twist
      when subjected to torque, which conforms to the tube deformation theory.

PMID- 22992800
TI  - Single-crystal investigation of L-tryptophan with Z' = 16.
AB  - A complex, disorder-free structure in the space group P1 has been established for
      L-tryptophan, for which no crystal structure has previously been available. The
      16 molecules in the asymmetric unit can be divided into two groups of eight; one
      where the side chains have gauche orientations and one with trans orientations.
      Molecules within each group have almost identical molecular geometries. The unit
      cell parameters mimic a hexagonal cell, but deviations from 90 degrees  for the
      cell angles alpha = 84.421 (4) and beta = 87.694 (4) degrees  give a small tilt
      that rules out hexagonal symmetry. The hydrogen-bonding pattern resembles that
      found in the crystal structure of the racemic structure of DL-tryptophan, but a
      lower density combined with longer hydrogen bonds and inter-aromatic interactions
      show that the enantiomeric structure is less efficiently packed.

PMID- 22992802
TI  - Delayed-type hypersensitivity to sand fly saliva in humans from a leishmaniasis
      endemic area of Mali is Th1-mediated and persists to midlife.
AB  - Immunity to sand fly saliva in rodents induces a T(H)1 delayed-type
      hypersensitivity (DTH) response conferring protection against leishmaniasis. The
      relevance of DTH to sand fly bites in humans living in a leishmaniasis-endemic
      area remains unknown. Here, we describe the duration and nature of DTH to sand
      fly saliva in humans from an endemic area of Mali. DTH was assessed at 24, 48,
      72, and 96 hours post bite in volunteers exposed to colony-bred sand flies.
      Dermal biopsies were obtained 48 hours post bite; cytokines were quantified from
      peripheral blood mononuclear cells (PBMCs) stimulated with sand fly saliva in
      vitro. A DTH response to bites was observed in 75% of individuals aged 1-15
      years, decreasing gradually to 48% by age 45, and dropping to 21% thereafter.
      Dermal biopsies were dominated by T lymphocytes and macrophages. Abundant
      expression of IFN-gamma and absence of T(H)2 cytokines establishes the T(H)1
      nature of this DTH response. PBMCs from 98% of individuals responded to sand fly
      saliva. Of these, 23% were polarized to a T(H)1 and 25% to a T(H)2 response. We
      demonstrate the durability and T(H)1 nature of DTH to sand fly bites in humans
      living in a cutaneous leishmaniasis-endemic area. A systemic T(H)2 response may
      explain why some individuals remain susceptible to disease.

PMID- 22992804
TI  - Targeted sequence capture and high-throughput sequencing in the molecular
      diagnosis of ichthyosis and other skin diseases.

PMID- 22992803
TI  - Tbx18 targets dermal condensates for labeling, isolation, and gene ablation
      during embryonic hair follicle formation.
AB  - How cell fate decisions of stem and progenitor cells are regulated by their
      microenvironment or niche is a central question in stem cell and regenerative
      biology. Although functional analysis of hair follicle epithelial stem cells by
      gene targeting is well established, the molecular and genetic characterization of
      the dermal counterpart during embryonic morphogenesis has been lacking because of
      the absence of cell type-specific drivers. Here, we report that T-box
      transcription factor Tbx18 specifically marks dermal papilla (DP) precursor cells
      during embryonic hair follicle morphogenesis. With Tbx18(LacZ), Tbx18(H2BGFP),
      and Tbx18(Cre) knock-in mouse models, we demonstrate LacZ and H2BGFP (nuclear
      green fluorescent protein) expression and Cre activity in dermal condensates of
      nascent first-wave hair follicles at E14.5. As Tbx18 expression becomes more
      widespread throughout the dermis at later developmental stages, we use tamoxifen
      inducible Cre-expressing mice, Tbx18(MerCreMer), to exclusively target DP
      precursor cells and their progeny. Finally, we ablate Tbx18 in full knockout
      mice, but find no perturbations in hair follicle formation, suggesting that Tbx18
      is dispensable for normal DP function. In summary, our study establishes Tbx18 as
      a genetic driver to target for the first time embryonic DP precursors for
      labeling, isolation, and gene ablation that will greatly enhance investigations
      into their molecular functions during hair follicle morphogenesis.

PMID- 22992805
TI  - IL-4 inhibits the melanogenesis of normal human melanocytes through the JAK2
      STAT6 signaling pathway.
AB  - Skin diseases can be characterized by their predominant CD4-positive T-helper
      (Th) cell profiles. Chronic dermatological conditions often give rise to abnormal
      skin pigmentation. To understand the role of Th cells in pigmentation, the
      effects of the major Th cell cytokines, IFNgamma, IL-4, and IL-17A, on
      melanogenesis were evaluated using cultured normal human melanocytes (NHMs)
      instead of relying on transformed melanoma cell lines. IL-4 directly inhibited
      melanogenesis in NHMs and downregulated both transcription and translation of
      melanogenesis-associated genes, such as microphthalmia-associated transcription
      factor (MITF) and dopachrome tautomerase. Despite the lack of a direct inhibition
      of melanin pigment synthesis, IFNgamma and IL-17A increased the synthesis of an
      antimelanogenic cytokine IL-6 in NHMs. IFNgamma activated signal transducers and
      activators of transcription 1 (STAT1) and STAT3 phosphorylation in NHMs, and IL-4
      increased the STAT3 and STAT6 phosphorylation. The differential phosphorylation
      profile of STAT proteins between IFNgamma and IL-4 may explain the difference in
      their effect on melanogenesis in NHMs. The IL-4-induced downregulation of
      melanogenesis was inhibited by treating NHMs with a JAK2 inhibitor AG490 or STAT6
      siRNA. In conclusion, the involvement of the IL-4-induced JAK2-STAT6 signaling
      and the IFNgamma- or IL-17A-dependent antimelanogenic IL-6 production should be
      considered as one of the mechanisms explaining the association with
      hypopigmention in skin diseases.

PMID- 22992807
TI  - [Enteral and parenteral nutrition].

PMID- 22992806
TI  - TNF-alpha and IFN-gamma are potential inducers of Fas-mediated keratinocyte
      apoptosis through activation of inducible nitric oxide synthase in toxic
      epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is a severe immune-mediated adverse cutaneous
      drug eruption characterized by rapid and extensive epithelial cell death in the
      epidermis and mucosae. The molecular events leading to this often fatal condition
      are only partially understood, but evidence suggests a dual mechanism implicating
      a "drug"-specific immune response on one side and the onset of target cell death
      by proapoptotic molecules including FasL on the other side. Herein, we describe a
      potential molecular bridge between these two events that involves inducible
      nitric oxide synthase (iNOS), which is highly upregulated in the skin of TEN
      patients. We show that activated T cells secrete high amounts of tumor necrosis
      factor-alpha (TNF-alpha) and IFN-gamma, and that both cytokines lead to increased
      expression and activity of keratinocyte iNOS. A similar observation has been made
      with drug-specific T lymphocytes from a TEN patient exposed to the culprit drug.
      The resulting increase in nitric oxide significantly upregulates keratinocyte
      FasL expression, resulting in Fas- and caspase-8-mediated keratinocyte cell
      death. Taken together, our data suggest that T-lymphocyte activation by drugs in
      TEN patients may indirectly lead to FasL-mediated keratinocyte apoptosis, via a
      molecular bridge involving TNF-alpha, IFN-gamma, and iNOS.

PMID- 22992809
TI  - Enhancement of gene transfer efficiency in the Bcap-37 cell line by dimethyl
      sulphoxide and menthol.
AB  - Simple and efficient gene transfer into the nucleus would facilitate non-viral
      gene delivery. One promising method of non-viral gene delivery is to apply
      penetration enhancers. Chemicals, such as dimethyl sulfoxide (DMSO) and menthol,
      may have promise as non-toxic vehicles in improving gene transfer efficiency. In
      this study, the cytotoxic effects of DMSO and menthol were evaluated using MTT
      assays. Gene delivery efficiency in a human breast cancer cell line (Bcap-37) was
      investigated by quantitative PCR, fluorescence microscopy and flow cytometry. Non
      toxic concentrations of DMSO (2%) and menthol (12.5 uM) enhanced the efficiency
      of liposome-mediated gene delivery in Bcap-37 cells. Quantitative PCR results
      showed that growth hormone (GH) mRNA expression in the post-menthol and pre-DMSO
      treatment groups was 10-fold higher compared to that in the liposome group, while
      in the pre-menthol and post-DMSO treatment groups, a 30-fold increase in GH mRNA
      expression was observed. Both DMSO and menthol treatments increased green
      fluorescent protein (GFP) expression efficiency as shown by fluorescence
      microscopy experiments. Compared to the liposome group, the number of positive
      cells in the pre-menthol and post-DMSO treatment groups was significantly
      increased by 15%. Furthermore, cell cycle analysis demonstrated that there were
      significant differences among the DMSO-treated group, the menthol-treated group
      and the normal group, which implied different effects of DMSO and menthol
      treatments. In conclusion, both non-toxic and harmless DMSO (2%) and menthol
      (12.5 uM) treatments improve gene transfer efficiency, while post-DMSO treatment
      may be the most effective protocol in increasing transgene expression efficiency.

PMID- 22992810
TI  - Impairment of the retinoic acid-inducible gene-I-IFN-beta signaling pathway in
      chronic hepatitis B virus infection.
AB  - Chronic hepatitis B (CHB) virus infection is caused by compromised host immunity,
      but the precise underlying mechanism remains unclear. Retinoic acid-inducible
      gene I (RIG-I) triggers antiviral immunity by inducing interferon-beta (IFN-beta)
      production following viral infection. To investigate the role of the RIG-I-IFN
      beta signaling pathway in monocyte-derived dendritic cells (moDCs) during CHB
      infection, moDCs were generated by stimulating CD14+ monocytes in vitro. MoDCs
      from patients with CHB, acute hepatitis B (AHB) and healthy controls (HCs) were
      challenged with vesicular stomatitis virus (VSV) and the levels of RIG-I, IFN
      beta promoter stimulator 1 (IPS-1) and IFN-beta in the stimulated moDCs were
      determined. Following 16 h of VSV stimulation, RIG-I expression was reduced by
      50% in moDCs from CHB patients and by 70% in moDCs from AHB patients relative to
      HC moDCs, concomitant with a 20% decrease in IFN-beta expression in CHB patients
      relative to AHB patients and HCs. Additionally, a significant correlation between
      the RIG-I/IPS-1 ratio and alanine aminotransferase (ALT) level was observed. To
      further investigate the function of RIG-I in chronic hepatitis B virus (HBV)
      infection, HepG2 or HepG2.2.15 (HBV-transformed) cell lines were challenged with
      VSV following RIG-1 transfection. IFN-beta induction was suppressed in HepG2.2.15
      cells, but was restored following RIG-I transfection. Taken together, these data
      indicate that compromised moDC function in CHB patients is attributable to an
      impaired RIG-I-IFN-beta signaling pathway, which results in compromised host
      viral clearance and HBV persistence in a susceptible population.

PMID- 22992811
TI  - A disease severity scoring system for children with type 1 Gaucher disease.
AB  - Almost half of patients with Gaucher disease are diagnosed by the age of 10
      years, and approximately two thirds are diagnosed by the age of 20 years. Besides
      symptomatic children, some presymptomatic children are being diagnosed through
      community screening programs and because of affected siblings. In addition, it is
      anticipated that in the near future, newborn screening for lysosomal diseases
      such as Gaucher disease will be introduced in the USA, identifying additional
      pre/nonsymptomatic children. Currently, there is no severity scoring system for
      children. A validated disease severity scoring system in the pediatric Gaucher
      population will be essential for classifying disease severity in these children,
      monitoring their disease progression, making decisions about when to treat them,
      and monitoring disease improvement with therapy. A severity scoring system will
      also be helpful in comparing therapeutic options as new therapies are designed.
      Therefore, a Pediatric Gaucher Severity Scoring System (PGS3) was devised using
      expert opinion and validated in 26 patients with type 1 Gaucher disease. The PGS3
      correlates well with disease severity in patients at diagnosis and over time.
      CONCLUSION: A practical system that will help clinical management, based on signs
      and symptoms in children with type 1 Gaucher disease, is presented.

PMID- 22992812
TI  - PELP1/MNAR suppression inhibits proliferation and metastasis of endometrial
      carcinoma cells.
AB  - Proline-, glutamic acid- and leucine-rich protein-1/modulator of non-genomic
      activity of estrogen receptor (ER) (PELP1/MNAR) is a novel nuclear receptor (NR)
      co-activator that plays an essential role in the actions of ER. Emerging findings
      suggest that PELP1/MNAR is a novel proto-oncogene, whose expression is
      deregulated in several hormone-responsive cancers, including endometrial cancer.
      In this study, we demonstrate that PELP1/MNAR is widely expressed in endometrial
      carcinoma cell lines. To investigate its possible role in endometrial carcinoma
      progression, we adopted an RNA interference technology to downregulate PELP1/MNAR
      expression in Ishikawa endometrial carcinoma cells. PELP1/MNAR downregulation
      substantially reduced cell proliferation, and the cells in which PELP1/MNAR
      expression was knocked down also exhibited a decreased migration and invasion
      ability, as shown by Boyden chamber and invasion assays. The results showed that
      the expression of MMP-2 and MMP-9 was also decreased. These results suggest that
      PELP1/MNAR plays a role in endometrial cancer progression and metastasis, and
      that PELP1/MNAR may be a potential therapeutic target for endometrial cancer.

PMID- 22992813
TI  - Pain management following total joint arthroplasty: making strides.

PMID- 22992814
TI  - Injection of the subacromial bursa in patients with rotator cuff syndrome: a
      prospective, randomized study comparing the effectiveness of different routes.
AB  - BACKGROUND: Rotator cuff syndrome is often treated with subacromial injection of
      corticosteroid and local anesthetic. It has not been established if the common
      injection routes of the bursa are equally accurate. METHODS: We conducted a
      prospective clinical trial involving seventy-five shoulders in seventy-five
      patients who were randomly assigned to receive a subacromial injection through an
      anterior, lateral, or posterior route with respect to the acromion. An
      experienced physician performed the injections, which contained radiopaque
      contrast medium, corticosteroid, and local anesthetic. After the injection, a
      musculoskeletal radiologist, blinded to the injection route, interpreted all of
      the radiographs. RESULTS: The rate of accuracy varied with the route of
      injection, with a rate of 56% for the posterior route, 84% for the anterior
      route, and 92% for the lateral route (p = 0.006; chi-square test). The accuracy
      of injection through the posterior route was significantly lower than that
      through either the anterior or the lateral route (p < 0.05 for both comparisons;
      Poisson regression). In addition, the accuracy of injection was significantly
      lower in females than in males (p < 0.006; chi-square test). Among males, no
      differences between the routes were noted (with accuracy rates of 89% for the
      posterior route, 92% for the anterior route, and 93% for the lateral route).
      Among females, however, the accuracy of injection was lower for the posterior
      route than for either the anterior or the lateral route (with accuracy rates of
      38% for the posterior route, 77% for the anterior route, and 91% for the lateral
      route) (p < 0.05). CONCLUSIONS: The anterior and lateral routes of subacromial
      bursal injection were more accurate than the posterior route. The accuracy of
      subacromial bursal injection was significantly different between males and
      females, mainly because of a lower accuracy of bursal injection with use of the
      posterior route in females. The present study suggests that the posterior route
      is the least accurate method for injection of the subacromial bursa in females.

PMID- 22992815
TI  - Macroscopic and microscopic analysis of the thumb carpometacarpal ligaments: a
      cadaveric study of ligament anatomy and histology.
AB  - BACKGROUND: Stability and mobility represent the paradoxical demands of the human
      thumb carpometacarpal joint, yet the structural origin of each functional demand
      is poorly defined. As many as sixteen and as few as four ligaments have been
      described as primary stabilizers, but controversy exists as to which ligaments
      are most important. We hypothesized that a comparative macroscopic and
      microscopic analysis of the ligaments of the thumb carpometacarpal joint would
      further define their role in joint stability. METHODS: Thirty cadaveric hands
      (ten fresh-frozen and twenty embalmed) from nineteen cadavers (eight female and
      eleven male; average age at the time of death, seventy-six years) were dissected,
      and the supporting ligaments of the thumb carpometacarpal joint were identified.
      Ligament width, length, and thickness were recorded for morphometric analysis and
      were compared with use of the Student t test. The dorsal and volar ligaments were
      excised from the fresh-frozen specimens and were stained with use of a triple
      staining immunofluorescent technique and underwent semiquantitative analysis of
      sensory innervation; half of these specimens were additionally analyzed for
      histomorphometric data. Mixed-effects linear regression was used to estimate
      differences between ligaments. RESULTS: Seven principal ligaments of the thumb
      carpometacarpal joint were identified: three dorsal deltoid-shaped ligaments
      (dorsal radial, dorsal central, posterior oblique), two volar ligaments (anterior
      oblique and ulnar collateral), and two ulnar ligaments (dorsal trapeziometacarpal
      and intermetacarpal). The dorsal ligaments were significantly thicker (p < 0.001)
      than the volar ligaments, with a significantly greater cellularity and greater
      sensory innervation compared with the anterior oblique ligament (p < 0.001). The
      anterior oblique ligament was consistently a thin structure with a histologic
      appearance of capsular tissue with low cellularity. CONCLUSIONS: The dorsal
      deltoid ligament complex is uniformly stout and robust; this ligament complex is
      the thickest morphometrically, has the highest cellularity histologically, and
      shows the greatest degree of sensory nerve endings. The hypocellular anterior
      oblique ligament is thin, is variable in its location, and is more structurally
      consistent with a capsular structure than a proper ligament.

PMID- 22992816
TI  - A comparison of MRI and CT imaging clarity of titanium alloy and titanium alloy
      with cobalt-chromium-alloy pedicle screw and rod implants in the lumbar spine.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) and computed tomography (CT) imaging
      are important postoperative diagnostic and evaluation tools, particularly in
      patients who have undergone spinal fusions. Advancements in materials and imaging
      techniques have lessened artifact and improved overall imaging results. Systems
      that combine titanium alloy and cobalt-chromium components have been introduced
      to reduce implant profile while maintaining strength. The objective of this study
      was to determine if there were any differences in the clarity of imaging between
      two types of implant materials in a lumbar spine construct model. METHODS: One of
      two lumbar spine stabilization implant systems, titanium alloy (titanium) or
      titanium alloy with cobalt-chromium alloy (titanium-cobalt), was placed to
      simulate a four-level fusion construct in two human cadaveric spine segments,
      followed by MRI and CT imaging. The implant systems were then removed from each
      cadaver and implanted in the other cadaver. Nine physician graders from three
      subspecialties scored the images using a 5-point scale, with higher imaging
      scores indicating greater clarity of the region of interest. Physician-rated
      scores were compared across systems and between physician groups. RESULTS: There
      were no significant differences in the overall mean total scores on the basis of
      construct material. Overall mean scores were 18.16 for titanium and 17.45 for
      titanium-cobalt (p = 0.275). Among images of the titanium-cobalt constructs, no
      significant differences in mean scores were found between specimens with use of
      MRI (p = 0.883) or with use of CT only (p = 0.274). Among images of the titanium
      system, a slightly significant difference was found between specimens with use of
      MRI (p = 0.044) but not with CT imaging (p = 0.837). CONCLUSIONS: Overall image
      clarity scores were not significantly different between titanium and titanium
      cobalt implant systems in the lumbar spine. Observation of pertinent anatomy in
      the regions of interest was not degraded by the presence of either system.

PMID- 22992817
TI  - Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis:
      the Carter effect.
AB  - BACKGROUND: Adolescent idiopathic scoliosis occurs between two and ten times more
      frequently in females than in males. The exact cause of this sex discrepancy is
      unknown, but it may represent a difference in susceptibility to the deformity. If
      this difference is attributable to genetic factors, then males with adolescent
      idiopathic scoliosis would need to inherit a greater number of susceptibility
      genes compared with females to develop the deformity. Males would also be more
      likely to transmit the disease to their children and to have siblings with
      adolescent idiopathic scoliosis. Such a phenomenon is known as the Carter effect,
      and the presence of such an effect would support a multifactorial threshold model
      of inheritance. METHODS: One hundred and forty multiplex families in which more
      than one individual was affected with adolescent idiopathic scoliosis were
      studied. These families contained 1616 individuals, including 474 individuals
      with adolescent idiopathic scoliosis and 1142 unaffected relatives. The rates of
      transmission from the 122 affected mothers and from the twenty-eight affected
      fathers were calculated, and the prevalence among siblings was determined in the
      nuclear families of affected individuals. RESULTS: The prevalence of adolescent
      idiopathic scoliosis in these multiplex families was lowest in sons of affected
      mothers (36%, thirty-eight of 105) and highest in daughters of affected fathers
      (85%, twenty-two of twenty-six). Affected fathers transmitted adolescent
      idiopathic scoliosis to 80% (thirty-seven) of forty-six children, whereas
      affected mothers transmitted it to 56% (133) of 239 children (p < 0.001).
      Siblings of affected males also had a significantly higher prevalence of
      adolescent idiopathic scoliosis (55%, sixty-one of 110) compared with siblings of
      affected females (45%, 206 of 462) (p = 0.04). CONCLUSIONS: This study
      demonstrates the presence of the Carter effect in adolescent idiopathic
      scoliosis. This pattern can be explained by polygenic inheritance of adolescent
      idiopathic scoliosis, with a greater genetic load required for males to be
      affected.

PMID- 22992818
TI  - Practice patterns for subacromial decompression and rotator cuff repair: an
      analysis of the American Board of Orthopaedic Surgery database.
AB  - BACKGROUND: Recently there have been several evolving trends in the practice of
      shoulder surgery. Arthroscopic subacromial decompression has been performed with
      greater frequency by orthopaedic surgeons, and there has been considerable recent
      interest in arthroscopic rotator cuff repair. The purpose of this study was to
      identify trends in practice patterns for subacromial decompression and rotator
      cuff repair over time and in relation to the location of practice, fellowship
      training, and declared subspecialty of the surgeon. METHODS: We reviewed the
      American Board of Orthopaedic Surgery Part II database to identify patterns in
      the utilization of open and arthroscopic subacromial decompression and rotator
      cuff repair among candidates for board certification. All procedures involving
      only arthroscopic or open subacromial decompression and/or rotator cuff repair
      from 2004 to 2009 were identified. The rates of arthroscopic and open subacromial
      decompression and/or rotator cuff repair were compared in terms of year,
      geographic region, fellowship training, and declared subspecialty of the surgeon.
      RESULTS: Between 2004 and 2009, 12,136 surgical procedures involving only
      arthroscopic or open subacromial decompression and/or rotator cuff repair were
      performed. There were significant differences in treatment with respect to year,
      geographic region of practice, declared subspecialty, and fellowship training (p
      < 0.001). There was a significant increase over time in the utilization of
      arthroscopy among all candidates (p < 0.001). Surgeons with sports medicine
      fellowship training or a sports-medicine-declared subspecialty performed
      significantly more subacromial decompressions and rotator cuff repairs
      arthroscopically than all other candidates (p < 0.001). During this time period,
      there was a significant decrease in the rate of arthroscopic subacromial
      decompression, both as an isolated procedure and combined with arthroscopic
      rotator cuff repair (p < 0.001). CONCLUSIONS: From 2004 to 2009, there was a
      significant shift throughout the United States toward arthroscopic rotator cuff
      repair and subacromial decompression among young orthopaedic surgeons, with
      sports medicine fellowship-trained surgeons performing more of their procedures
      arthroscopically than surgeons with other training. However, there was an
      increasing frequency of arthroscopic rotator cuff repair performed without
      subacromial decompression, and, overall, there was a decrease in the frequency of
      isolated arthroscopic subacromial decompression over time.

PMID- 22992819
TI  - The association between body mass index and the outcomes of total knee
      arthroplasty.
AB  - BACKGROUND: In the United Kingdom, organizations involved in health-care
      commissioning have recently introduced legislation limiting access to total knee
      arthroplasty through the introduction of arbitrary thresholds unsupported by the
      literature and based on body mass index. This study aimed to establish the
      relationship between body mass index and patient-reported specific and general
      outcomes on total knee arthroplasty. METHODS: Using national patient-reported
      outcome measures (PROMs) linked to the National Joint Registry, we identified
      13,673 primary total knee arthroplasties performed for the treatment of
      osteoarthritis. The PROMs project involves the collection of condition-specific
      and general health outcomes before and at six months following total knee
      arthroplasty. The relationships between body mass index and the Oxford Knee
      Score, EuroQol 5D index, and EuroQol 5D Visual Analogue Scale were assessed with
      use of scatterplots and linear regression. The improvement in these measures was
      compared for three distinct groups based on body mass index (Group I [15 to 24.9
      kg/m(2)], Group II [25 to 39.9 kg/m(2)], and Group III [40 to 60 kg/m(2)]) with
      use of multiple regression analysis to adjust for differences in age, sex,
      American Society of Anesthesiologists grade, general health rating, and number of
      comorbidities. RESULTS: The preoperative and postoperative patient-reported
      outcome measures declined to a similar extent with increasing body mass index.
      The gradient of the linear regression equation relating to the change in scores
      was positive in all cases, indicating that there was a tendency for scores to
      improve to a greater extent as body mass index increased. After adjustment, the
      changes in patient-reported outcome measures in Group I and Group III were
      equivalent for the Oxford Knee Score (mean difference, 0.5 point [95% confidence
      interval, -0.5 to 1.5 points]; p = 0.78), the EuroQol 5D index (mean difference,
      0.014 point [95% confidence interval, -0.021 to 0.048 point]; p = 1.00), and the
      EuroQol 5D Visual Analogue Scale (mean difference, 1.9 points [95% confidence
      interval, -0.4 to 4.1 points]; p = 0.13). Wound complications were significantly
      higher (p < 0.001) at a rate of 17% (168 of 1018 patients) in Group III compared
      with 9% (121 of 1292 patients) in Group I. CONCLUSIONS: The improvements in
      patient-reported outcome measures experienced by patients were similar,
      irrespective of body mass index. Health policy should be based on the overall
      improvements in function and general health gained through surgery. Obese
      patients should not be excluded from the benefit of total knee arthroplasty,
      given that their overall improvements were equivalent to those of patients with a
      lower body mass index.

PMID- 22992820
TI  - Intra-articular infusion of anesthetic provided more pain relief than extra
      articular infusion during mobilization after total knee arthroplasty.

PMID- 22992821
TI  - Surgical timing of treating injured extremities.

PMID- 22992823
TI  - Progression of periacetabular osteolytic lesions.
AB  - BACKGROUND: The development of three-dimensional computed tomography (CT) imaging
      techniques has enabled the detection, accurate measurement, and monitoring of
      periprosthetic osteolytic lesions. The aim of this study was to track the
      progression in size of osteolytic lesions and to determine those factors that are
      associated with the risk of progression. A secondary aim was to investigate
      whether progression in size of osteolytic lesions could be monitored with use of
      radiographs. METHODS: We retrospectively determined, with use of sequential CT
      scans, the progression of periacetabular osteolysis over a period of as much as
      nine years in a cohort of twenty-six patients (thirty acetabular components) in
      whom the cementless acetabular component or components had been in place for
      longer than ten years at the time of the initial CT scan. High-resolution CT
      scans with metal-artifact suppression were used to determine the volume of
      osteolytic lesions. Progression in the size of osteolytic lesions per year was
      calculated as the change in the volume of osteolytic lesions between serial CT
      scans. Associations were determined between the progression in size of osteolytic
      lesions, osteolysis rate at the initial CT, patient age, sex, walking
      limitations, and activity level. Progression in size of osteolytic lesions as
      determined with use of CT was compared with that determined with use of
      radiographs. RESULTS: Mean progression in the size of osteolytic lesions, as
      determined with use of CT, was 1.5 cm(3)/yr (range, 0 to 7.5 cm(3)/yr). The
      amount of osteolysis at the initial CT scan and patient activity were good
      predictors of osteolytic lesion progression. The strongest predictor of
      osteolytic lesion progression occurred when these two risk factors were combined
      (p = 0.0019). The value of radiographs was limited to monitoring of larger
      lesions identified by CT. CONCLUSIONS: This is the first study to report on the
      progression of osteolysis adjacent to cementless acetabular components from
      medium to long-term follow-up. The data suggest that the osteolysis rate at the
      initial CT and patient activity can be useful factors in predicting the
      progression in size of periacetabular osteolytic lesions.

PMID- 22992824
TI  - The paradoxical McMurray test for the detection of meniscal tears: an
      arthroscopic study of mechanisms, types, and accuracy.
AB  - BACKGROUND: Meniscal tears are very common. The so-called paradoxical McMurray
      test has been described and found to be positive for three different types of
      meniscal tears. However, to our knowledge, no study has evaluated the accuracy of
      this test. The purpose of the present study was to evaluate the accuracy of the
      paradoxical McMurray test compared with the conventional McMurray test. We also
      sought to determine whether there are other types of meniscal tears that would
      show positive results on the paradoxical McMurray test. METHODS: The authors
      evaluated 628 patients with meniscal tears (Group I) and 387 patients without
      meniscal tears (Group II), as confirmed by arthroscopy performed from June 2000
      to May 2006. The results of both clinical examinations (the conventional and the
      paradoxical McMurray test) were recorded, and the paradoxical phenomenon as seen
      during arthroscopy was described. The sensitivity and specificity of each test
      were calculated and statistically analyzed. RESULTS: The average patient age (and
      standard deviation) was 41.9 +/- 15.6 years (range, ten to sixty-six years) in
      Group I and 40.3 +/- 12.9 years (range, fifteen to sixty-three years) in Group
      II. The sensitivities of the McMurray test and the paradoxical McMurray test for
      diagnosing a meniscal tear were 41.9% (263 of 628) and 12.3% (seventy-seven of
      628), respectively. The specificities of the two tests were 76.7% (297 of 387)
      and 99.2% (384 of 387), respectively. Compared with the conventional McMurray
      test, the paradoxical McMurray test showed significantly lower sensitivity but
      higher specificity. Apart from the three previously reported types of meniscal
      tears, a new type of meniscal tear in a discoid lateral meniscus also showed
      positive results with the paradoxical McMurray tests. CONCLUSIONS: In conclusion,
      a positive paradoxical McMurray test is reliable for diagnosing a meniscal tear
      that has a large displaced meniscal flap. A long radial tear in the posterior one
      third of the discoid lateral meniscus is a new type of meniscal tear with
      positive results on the paradoxical McMurray test.

PMID- 22992825
TI  - Reoperations following combat-related upper-extremity amputations.
AB  - BACKGROUND: Amputation revision rates following major upper-extremity amputations
      have not been previously reported in a large cohort of patients. We hypothesized
      that the revision rates following major upper-extremity amputation were higher
      than the existing literature would suggest, and that surgical treatment of
      complications and persistent symptoms would lead to improved outcomes. METHODS:
      We performed a retrospective analysis of a consecutive series of ninety-six
      combat-wounded personnel who had sustained a total of 100 major upper-extremity
      amputations in Operation Iraqi Freedom and Operation Enduring Freedom.
      Prerevision and postrevision outcome measures, including prosthesis use and type,
      the presence of phantom and residual limb pain, pain medication use, and return
      to active military duty, were identified for all patients. RESULTS: All
      amputations resulted from high-energy trauma, with 87% occurring secondary to a
      blast injury. Forty-two residual limbs (42%) underwent a total of 103 repeat
      surgical interventions. As compared with patients with all other levels of
      amputation, those with a transradial amputation were 4.7 (95% confidence interval
      [CI]: 1.75 to 12.46) times more likely to have phantom limb pain and 2.8 (95% CI:
      1.04 to 7.39) times more likely to require neuropathic pain medications. In the
      group of patients who underwent revision surgery, regular prosthesis use
      increased from 19% before the revision to 87% after it (p < 0.0001). CONCLUSIONS:
      In our cohort, revision amputation to address surgical complications and
      persistently symptomatic residual limbs improved the patient's overall acceptance
      of the prosthesis and led to outcomes equivalent to those following amputations
      that did not require revision.

PMID- 22992826
TI  - Carpal tunnel syndrome and radiographically evident basal joint arthritis of the
      thumb in elderly Koreans.
AB  - BACKGROUND: Previous studies have suggested a high prevalence of carpal tunnel
      syndrome in patients seeking treatment for basal joint arthritis of the thumb.
      The purpose of this study was to compare the prevalence of carpal tunnel syndrome
      between individuals with and those without radiographic evidence of basal joint
      arthritis of the thumb in the general elderly Korean population, and to determine
      if there is a correlation between the severity of carpal tunnel syndrome shown by
      electrophysiological studies and the severity of basal joint arthritis as seen on
      radiographs. METHODS: We evaluated hand radiographs and nerve conduction studies
      of 192 men and 176 women (more than sixty-five years of age) who participated in
      the Korean Longitudinal Study on Health and Aging. The basal joint of the thumb
      was assigned a grade for osteoarthritis of 0 to 4 on radiographs with use of the
      Kellgren and Lawrence criteria. The diagnosis of carpal tunnel syndrome was based
      on the combination of a positive response to survey questions and a positive
      nerve conduction study. Motor distal latency and motor conduction velocity were
      measured to assess the electrophysiological severity of carpal tunnel syndrome.
      RESULTS: The prevalence of carpal tunnel syndrome was 16.7% in the group with
      basal joint arthritis and 10.9% in the group without basal joint arthritis, a
      difference that was not significant (p = 0.249). Neither motor distal latency nor
      motor conduction velocity was significantly correlated with the severity of the
      basal joint arthritis in the entire group of 368 study subjects (p = 0.154 and p
      = 0.662, respectively) or in those with carpal tunnel syndrome (p = 0.603 and p =
      0.998, respectively). CONCLUSIONS: This study of Koreans who were more than sixty
      five years of age showed that the prevalence of carpal tunnel syndrome is similar
      in patients with and those without radiographic findings of basal joint arthritis
      of the thumb. We found no correlation between the electrophysiological severity
      of carpal tunnel syndrome and the severity of basal joint arthritis.

PMID- 22992827
TI  - Peripheral nerve injuries in sports-related surgery: presentation, evaluation,
      and management: AAOS exhibit selection.
AB  - Peripheral nerve injuries during sports-related operative interventions are rare
      complications, but the associated morbidity can be substantial. Early diagnosis,
      efficient and effective evaluation, and appropriate management are crucial to
      maximizing the prognosis, and a clear and structured algorithm is therefore
      required. We describe the surgical conditions and interventions that are commonly
      associated with intraoperative peripheral nerve injuries. In addition, we review
      the common postoperative presentations of patients with these injuries as well as
      the anatomic structures that are directly injured or associated with these
      injuries during the operation. Some examples of peripheral nerve injuries
      incurred during sports-related surgery include ulnar nerve injury during ulnar
      collateral ligament reconstruction of the elbow and elbow arthroscopy, median
      nerve injury during ulnar collateral ligament reconstruction of the elbow,
      axillary nerve injury during Bankart repair and the Bristow transfer, and
      peroneal nerve injury during posterolateral corner reconstruction of the knee and
      arthroscopic lateral meniscal repair. We also detail the clinical and
      radiographic evaluation of these patients, including the utility and timing of
      radiographs, magnetic resonance imaging (MRI), ultrasonography, electromyography
      (EMG), and nonoperative or operative management. The diagnosis, evaluation, and
      management of peripheral nerve injuries incurred during sports-related surgical
      interventions are critical to minimizing patient morbidity and maximizing
      postoperative function. Although these injuries occur during a variety of
      procedures, common themes exist regarding evaluation techniques and treatment
      algorithms. Nonoperative treatment includes physical therapy and medical
      management. Operative treatments include neurolysis, transposition, neurorrhaphy,
      nerve transfer, and tendon transfer. This article provides orthopaedic surgeons
      with a simplified, literature-based algorithm for evaluation and management of
      peripheral nerve injuries associated with sports-related operative procedures.

PMID- 22992828
TI  - The subacromial space: how to get a needle there: commentary on an article by
      Richard A. Marder, MD, et al.: "Injection of the subacromial bursa in patients
      with rotator cuff syndrome. A prospective, randomized study comparing the
      effectiveness of different routes".

PMID- 22992829
TI  - Higher genetic threshold for progressive adolescent idiopathic scoliosis in male
      individuals: commentary on an article by Lisa M. Kruse, MD, et al.: "Polygenic
      threshold model with sex dimorphism in adolescent idiopathic scoliosis: the
      Carter effect".

PMID- 22992830
TI  - Targeting of liposomes via PSGL1 for enhanced tumor accumulation.
AB  - PURPOSE: To improve the delivery of liposomes to tumors using P-selectin
      glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are
      upregulated on tumorassociated endothelium. METHODS: PSGL1 was orientated and
      presented on the surface of liposomes to achieve optimal selectin binding using a
      novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with
      luciferin allowed their binding to e-selectin and activated HUVEC to be
      quantified in vitro and their stability, pharmacokinetics and tumor accumulation
      to be tested in vivo using murine models. RESULTS: PSGL1 liposomes showed 5-fold
      (p < 0.05) greater selectin binding than identically formulated control liposomes
      modified with ligand that did not contain the selectin binding domain. When added
      to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than
      control liposomes. In in vivo studies PSGL1 liposomes showed similar stability
      and circulation to control liposomes but demonstrated a >3-fold enhancement in
      the level of delivery to tumors (p < 0.05). CONCLUSIONS: The technologies and
      strategies described here may contribute to clinical improvements in the
      selectivity and efficacy of liposomal drug delivery agents.

PMID- 22992831
TI  - PEGylated multi-walled carbon nanotubes for encapsulation and sustained release
      of oxaliplatin.
AB  - PURPOSE: To develop PEGylated multi-walled carbon nanotubes as a sustained
      release drug delivery system. METHODS: Oxaliplatin was incorporated into inner
      cavity of PEGylated multi-walled carbon nanotubes (MWCNT-PEG) using nano
      extraction. Oxaliplatin release rates from MWCNT-PEG-Oxaliplatin were
      investigated using dialysis tubing. Cytotoxicity of oxaliplatin, MWCNT
      Oxaliplatin and MWCNT-PEG-Oxaliplatin were evaluated in HT29 cell by MTT assay,
      Pt-DNA adducts formation, gamma-H2AX formation and cell apoptosis assay. RESULTS:
      Loading of oxaliplatin into MWCNT-PEG was ~43.6%. Sustained release occurred to
      MWCNT-PEG-Oxaliplatin, with only 34% of oxaliplatin released into medium within 6
      h. In MTT assay, MWCNT-PEG-Oxaliplatin showed slightly decreased cytotoxic effect
      when cell viability was assessed at 12 and 24 h. A drastic increase of
      cytotoxicity was found when cell viability was assessed at 48 and 96 h. Pt-DNA
      adducts formation, gamma-H2AX formation and cell apoptosis assay results showed
      the same trend as the MTT assay, suggesting sustained-release for MWCNT
      Oxaliplatin and MWCNT-PEG-Oxaliplatin formulations. CONCLUSIONS: PEGylated multi
      walled carbon nanotubes can be used as sustained release drug delivery system,
      thus remarkably improving cytotoxicity of oxaliplatin on HT-29 cells.

PMID- 22992832
TI  - Rapid lymph accumulation of polystyrene nanoparticles following pulmonary
      administration.
AB  - PURPOSE: Pulmonary administration of polymeric nanoparticle drug delivery systems
      is of great interest for both systemic and local therapies. However, little is
      understood about the relationship of particle size and pulmonary absorption. We
      investigated uptake and biodistribution of polystyrene nanoparticles (PN) of 50
      nm, 100 nm, 250 nm, and 900 nm diameters in mice following administration to
      lungs via pharyngeal aspiration. METHODS: The amount of PN in tissues was
      analyzed by gel permeation chromatography (GPC). RESULTS: At 1 h, larger diameter
      PN (250 nm and 900 nm) had the highest total uptake at around 15% of administered
      dose, whereas the smaller diameter PN (50 nm and 100 nm) had uptake of only 5-6%.
      However, at 3 h, the 50 nm PN had the highest total uptake at 24.4%. For each
      size tested, the highest nanoparticle deposition was observed in the lymph nodes
      (LN) as compared to other tissues accounting for a total of about 35-50% of
      absorbed nanoparticles. CONCLUSION: PN size impacts the rate and extent of uptake
      from lungs and, further, the extent of LN deposition. The extent of uptake and
      lymph distribution of the model, non-degradable PN lends potential to pulmonary
      administered, biodegradable polymeric nanoparticles for delivery of therapeutics
      to regional lymph nodes.

PMID- 22992833
TI  - Standing surface acoustic wave (SSAW) based multichannel cell sorting.
AB  - We introduce a novel microfluidic device for cell sorting in continuous flow
      using tunable standing surface acoustic waves. This method allows individual
      cells to be precisely directed into five different outlet channels in a single
      step. It is versatile, simple, label-free, non-invasive, and highly controllable.

PMID- 22992835
TI  - Case of endogenous endophthalmitis caused by Klebsiella pneumoniae with magA and
      rmpA genes in an immunocompetent patient.
AB  - We report a case of endogenous endophthalmitis caused by Klebsiella pneumoniae in
      an immunocompetent patient. A 73-year-old man with acute epididymitis who had no
      history of diabetes mellitus developed endogenous endophthalmitis. The patient
      underwent anterior vitrectomy and intracapsular cataract extraction with
      intravitreal injections of both vancomycin and ceftazidime. After the surgery, he
      was treated with topical and intravenous antibiotics; however, the left eye
      perforated and was enucleated. Culture from vitreous biopsy specimens grew as K.
      pneumoniae, which was positive for both magA and rmpA. K. pneumoniae should be
      considered as a pathogen that can cause severe endogenous endophthalmitis in
      patients with urinary tract infection. The severity of the disease may be related
      to the virulence genes.

PMID- 22992836
TI  - Delftia acidovorans bacteremia caused by bacterial translocation after
      organophosphorus poisoning in an immunocompetent adult patient.
AB  - A 46-year-old woman was transferred to our emergency unit because of impaired
      consciousness and respiratory failure with the history of excessive pesticide
      intake. The patient was hypersalivative and had bilateral pupillary miosis.
      Laboratory results showed markedly decreased cholinesterase. She was intubated
      and treated in the intensive care unit with the diagnosis of organophosphorus
      poisoning. The patient had persisted diarrhea, with a high fever and stomach
      tenderness on day 10. Whole-body contrast enhanced computed tomography revealed a
      swollen, enhanced small intestinal wall, and blood culture identified Delftia
      acidovorans. She was diagnosed as D. acidovorans bacteremia, probably caused by
      bacterial translocation based on the clinical presentation and the exclusion of
      other sources, and treated well with a total of 8 days of antibiotic therapy. So
      far as we know, this is the first case of D. acidovorans bacteremia that was
      presumably caused by bacterial translocation after organophosphorus poisoning in
      an immunocompetent adult patient.

PMID- 22992837
TI  - Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer
      cells.
AB  - The purpose of this study was to determine the effects of baicalein and wogonin,
      which are compounds derived from the Chinese herb Scutellaria baicalensis, in
      suppressing the viability of HT-29 human colon cancer cells. Following treatment
      with baicalein or wogonin, several apoptotic events were observed, including DNA
      fragmentation, chromatin condensation and increased cell cycle arrest in the G1
      phase. Baicalein and wogonin decreased Bcl-2 expression, whereas the expression
      of Bax was increased in a dose-dependent manner compared with the control.
      Furthermore, the induction of apoptosis was accompanied by an inactivation of
      phosphatidylinositol 3-kinase (PI3K)/Akt in a dose-dependent manner. The
      administration of baicalein to mice resulted in the inhibition of the growth of
      HT-29 xenografts without any toxicity following 5 weeks of treatment. The results
      indicated that baicalein induced apoptosis via Akt activation in a p53-dependent
      manner in the HT-29 colon cancer cells and that it may serve as a chemopreventive
      or therapeutic agent for HT-29 colon cancer.

PMID- 22992838
TI  - Regulation of mammalian MOR-1 gene expression after chronic treatment with
      morphine.
AB  - Morphine is an effective analgesic that acts by binding to the u-opioid receptor
      (MOR) coded in the human by the OPRM1 gene. In the present study, we investigated
      the regulation of u-opioid receptor (MOR-1) mRNA levels in all-trans-retinoic
      acid-differentiated SH-SY5Y human neuroblastoma cells under in vitro conditions
      with 10 uM morphine treatment for 24 h. In addition, we measured the MOR-1 levels
      in recombinant Chinese hamster ovary (CHO) cells, transfected with human u-opioid
      receptor gene (hMOR) with 10 uM morphine treatment for 24 h. The isolated mRNA
      from these cells was subjected to real-time quantitative RT-PCR analysis to
      determine the regulation of u-opioid receptor gene expression. It was observed
      that morphine treatment did not alter MOR-1 levels in undifferentiated SH-SY5Y
      cells compared to undifferentiated control cells. However, the MOR-1 levels in
      all-trans-retinoic acid-differentiated cells were significantly higher compared
      to the undifferentiated cells. Morphine treatment in differentiated SH-SY5Y cells
      caused significant downregulation of MOR-1 expression compared to the control
      cells. In the morphine-treated CHO cells, the hMOR-1 mRNA levels remained the
      same as the untreated control. Finally, pretreatment of SH-SY5Y cells with 10 uM
      naloxone, the antagonist of u-opioid receptor, for 1 h significantly blocked the
      downregulation of MOR-1 mRNA levels with morphine treatment. These findings
      suggest that regulation of MOR-1 gene expression is cell-type specific after
      chronic morphine treatment and provide some evidence in the understanding of
      morphine tolerance.

PMID- 22992839
TI  - Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and
      treatment.
AB  - Cytomegalovirus (CMV) is one of the most important pathogens that infect solid
      organ transplant recipients. CMV is associated with increased morbidity and
      mortality in this population as a result of its numerous direct and indirect
      effects. Prevention strategies consist of preemptive therapy and antiviral
      prophylaxis, and the choice of which preventive approach to implement should be
      guided by advantages and drawbacks related to the population being managed. There
      are differences in the approaches to the laboratory diagnosis and treatment of
      CMV infection and disease depending on assay availability, clinical presentation,
      disease severity, and specific transplant populations. In this article, the
      authors aim to summarize recent publications and updates in the epidemiology,
      diagnosis, prevention, and treatment of CMV infection in solid organ transplant
      recipients during the past year, including a brief review of future directions in
      the field.

PMID- 22992840
TI  - Characterization of the low pH/low nutrient-resistant LNCaP cell subline LNCaP
      F10.
AB  - Intratumoral regions of low extracellular pH and low nutrition are common
      features of solid tumors. Although cancer cells normally die when they are
      removed from their environment, a small population of cells survive. In the
      present study, the subline LNCaP-F10, of the prostate cancer cell line LNCaP, was
      isolated and its low pH/low nutrient-resistant properties were examined. LNCaP
      F10 cells were grown under low-pH/low-nutrient conditions, which caused cell
      death of the LNCaP cells. The cell death was associated with oligonucleosomal DNA
      fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage, indicating that
      low-pH/low-nutrient induced apoptosis in these cells. Significant differences in
      the expression of BCL2, BIRC5 and DAPK1 were detected between LNCaP-F10 and LNCaP
      cells. Tumor growth caused by implantation of LNCaP-F10 cells into the renal
      subcapsular space of nude mice in the absence or presence of prostate stromal
      cell stimulation was greater than that caused by implantation of LNCaP cells.
      LNCaP-F10 cells were resistant to apoptosis induced by an environment of low
      pH/low-nutrient in vitro, and displayed malignant potential in vivo.

PMID- 22992841
TI  - In-gel phosphatase assay using non-denaturing two-dimensional electrophoresis.
AB  - We developed a method for detecting phosphatase activities in crude tissue
      extracts after separation of proteins by a novel non-denaturing two-dimensional
      electrophoresis. In the first dimension, protein samples were separated by a
      MicroRotofor, a liquid-phase isoelectric focusing, in the presence or absence of
      urea. In the second dimension, fractionated proteins by the MicroRotofor were
      resolved by a native polyacrylamide gel electrophoresis in the presence of 20 mM
      2-mercaptoethanol. After electrophoresis, the polyacrylamide gel was directly
      immersed in a reaction mixture containing 4-methylumbelliferyl phosphate (MUP), a
      fluorogenic substrate, and phosphatase activities were detected as fluorescent
      bands. In this assay, a variety of phosphatase activities were clearly detected
      in gel when the tissue extracts were separated by the MicroRotofor in the
      presence of 1.5 M urea. Furthermore, after detecting phosphatase activities in
      polyacrylamide gel at neutral pH, its activities at acidic pH could be detected
      by immersing the gel in sodium citrate buffer (pH 3.0). Therefore, this method is
      a quite useful technique to analyze various phosphatases by sequential reactions
      with MUP under different conditions after sample separation by the two
      dimensional electrophoresis.

PMID- 22992842
TI  - The impact of Aggrus/podoplanin on platelet aggregation and tumour metastasis.
AB  - Platelets are small blood components that play indispensable roles in the initial
      stages of coagulation. In addition to their role in haemostasis, platelets
      participate in inflammation and tissue regeneration under physiological
      conditions. Recent studies also revealed the role of platelets under pathological
      conditions, including the oncogenic process. Platelets enhance tumour growth and
      metastasis by secreting many growth factors and angiogenic factors or by forming
      a coat around tumour cells in the blood stream. We previously discovered Aggrus
      (also known as podoplanin, gp36, gp38P, T1alpha and OTS-8) expressed on tumour
      cell surfaces as a key molecule for tumour-induced platelet aggregation. Aggrus
      expression is increased in various malignant tumours such as squamous cell
      carcinomas, mesotheliomas, glioblastomas and osteosarcomas. Detailed analysis
      revealed that Aggrus contains three tandem repeats of platelet aggregation
      stimulating (PLAG) domains that are associated with its platelet aggregation
      inducing ability. PLAG domains of Aggrus are involved in binding to its platelet
      receptor, C-type lectin-like receptor 2 (CLEC-2). Neutralizing monoclonal
      antibodies that interfere with Aggrus-CLEC-2 binding attenuate Aggrus-induced
      platelet aggregation, tumour cell growth and metastasis formation. Aggrus is also
      expressed in advanced atherosclerotic lesions, suggesting that Aggrus is
      associated with thrombus formation on disrupted atherosclerotic lesions. These
      data suggest that Aggrus is a promising cell surface target for developing new
      therapies against cancer and thrombosis.

PMID- 22992843
TI  - Malthusian dynamics in a diverging Europe: Northern Italy, 1650-1881.
AB  - Recent empirical research questions the validity of using Malthusian theory in
      preindustrial England. Using real wage and vital rate data for the years 1650
      1881, I provide empirical estimates for a different region: Northern Italy. The
      empirical methodology is theoretically underpinned by a simple Malthusian model,
      in which population, real wages, and vital rates are determined endogenously. My
      findings strongly support the existence of a Malthusian economy wherein
      population growth decreased living standards, which in turn influenced vital
      rates. However, these results also demonstrate how the system is best
      characterized as one of weak homeostasis. Furthermore, there is no evidence of
      Boserupian effects given that increases in population failed to spur any
      sustained technological progress.

PMID- 22992845
TI  - Meta-Analyses and Systematic Reviews: New Guidelines for JBJS.

PMID- 22992844
TI  - Patterning microscale extracellular matrices to study endothelial and cancer cell
      interactions in vitro.
AB  - The extracellular matrix (ECM) of the tumor niche provides support to residing
      and migrating cells and presents instructive cues that influence cellular
      behaviours. The ECM protein fibronectin (Fn) enables vascular network formation,
      while hyaluronic acid (HA) is known to facilitate breast tumor development. To
      recapitulate aspects of the tumor microenvironment, we developed systems of
      spatially defined Fn and HA for the co-culture of endothelial colony forming
      cells (ECFCs) and breast cancer cells (BCCs). A micropatterned system was
      developed using sequential microcontact printing of HA and Fn. This approach
      supported the preferential adhesion of ECFCs to Fn, but did not support the
      preferential adhesion of BCCs to HA. Thus, we developed a microstructured analog
      to spatially organize BCC-laden HA micromolded hydrogels adjacent to ECFCs in
      fibrin hydrogels. These novel, miniaturized systems allow the analysis of the
      spatial and temporal mechanisms regulating tumor angiogenesis, and can be applied
      to mimic other microenvironments of healthy and diseased tissues.

PMID- 22992846
TI  - Two to twenty-year survivorship of the hip in 810 patients with operatively
      treated acetabular fractures.
AB  - BACKGROUND: The aims of the study were (1) to determine the cumulative two to
      twenty-year survivorship of the hip after open reduction and internal fixation of
      displaced acetabular fractures, (2) to identify factors predicting conversion to
      total hip arthroplasty or hip arthrodesis, and (3) to create a predictive model
      that calculates an individual's probability of early need for total hip
      arthroplasty or hip arthrodesis. METHODS: Eight hundred and sixteen acetabular
      fractures treated with open reduction and internal fixation by one surgeon over a
      twenty-six-year period were analyzed. Cumulative two to twenty-year Kaplan-Meier
      survivorship analyses of the hip, including best and worst-case scenarios, were
      performed with total hip arthroplasty or hip arthrodesis as the end point.
      Univariate and multivariate Cox regression analyses were performed to identify
      negative predictors, which were then used to construct a nomogram for predicting
      an individual's probability of needing an early total hip arthroplasty. RESULTS:
      The cumulative twenty-year survivorship of the 816 hips available for follow-up
      was 79% at twenty years. The best and worst-case scenarios corresponded to
      cumulative twenty-year survivorship of 86% and 52%, respectively. Significant
      independent negative predictors were nonanatomical fracture reduction, an age of
      more than forty years, anterior hip dislocation, postoperative incongruence of
      the acetabular roof, involvement of the posterior acetabular wall, acetabular
      impaction, a femoral head cartilage lesion, initial displacement of the articular
      surface of >= 20 mm, and utilization of the extended iliofemoral approach.
      CONCLUSIONS: Open reduction and internal fixation of displaced acetabular
      fractures was able to successfully prevent the need for subsequent total hip
      arthroplasty within twenty years in 79% of the patients. The results represent
      benchmark comparative data for any future and past studies on the outcome of
      surgical fixation of acetabular fractures.

PMID- 22992847
TI  - Cementless metaphyseal fitting anatomic total hip arthroplasty with a ceramic-on
      ceramic bearing in patients thirty years of age or younger.
AB  - BACKGROUND: The number of midterm or long-term studies on the current generation
      of cementless total hip replacements with alumina-on-alumina ceramic bearings in
      patients younger than thirty years of age is limited. The purpose of this study
      was to evaluate the midterm results of the cementless metaphyseal fitting
      anatomic total hip prosthesis in patients younger than thirty years of age, with
      a particular emphasis on the prevalence of thigh pain, resorption of bone due to
      stress-shielding of the proximal part of the femur, aseptic loosening, and
      osteolysis. METHODS: We reviewed the cases of ninety-six patients (127 hips) who
      had a cementless total hip arthroplasty when they were thirty years or younger at
      the time of surgery. All surgical procedures were performed by a single surgeon.
      The most common diagnoses were osteonecrosis (54.3%) and developmental dysplasia
      of the hip (20.5%). Demographic data, the Harris hip score, Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC), and University of California,
      Los Angeles (UCLA) activity scores were recorded. Radiographic evaluation was
      used to evaluate implant fixation and osteolysis. The minimum follow-up interval
      was ten years (mean, 14.6 years; range, ten to sixteen years). RESULTS: The mean
      preoperative Harris hip score, WOMAC score, and UCLA activity score were 41
      points, 66 points, and 3 points, respectively. At the time of final follow-up,
      the mean Harris hip score, WOMAC score, and UCLA activity score were 95 points,
      16 points, and 8 points, respectively. No patient had thigh pain after one year
      postoperatively. All of the femoral stems and all but one of the acetabular
      components were well-fixed at the time of final follow-up. No hip exhibited
      squeaking, ceramic fracture, loosening, or osteolysis at the time of the final
      follow-up. CONCLUSIONS: These results in patients thirty years of age or younger
      suggest that the cementless metaphyseal fitting anatomic total hip prosthesis
      provides outstanding midterm fixation and substantial pain relief well into the
      second decade postoperatively. Moreover, the alumina-on-alumina ceramic bearing
      provides a high rate of survivorship without osteolysis.

PMID- 22992848
TI  - Effect of scapular orientation on shoulder internal impingement in a cadaveric
      model of the cocking phase of throwing.
AB  - BACKGROUND: Although deviations in scapular orientation are thought to predispose
      to shoulder injuries in throwing athletes, the biomechanical mechanism underlying
      shoulder injuries in throwing athletes with an altered scapular orientation
      remains unclear. METHODS: Seven fresh-frozen cadaveric shoulders were evaluated
      at 90 degrees  of abduction, with the humerus externally rotated from 90 degrees 
      to the maximum angle, to simulate the late cocking phase of the throwing motion.
      Loads were applied to the deltoid, pectoralis major, latissimus dorsi, teres
      major, and all rotator cuff muscles. Contact pressure in the glenohumeral joint
      was measured with use of a pressure sensor. The area of internal impingement was
      calculated on the basis of three-dimensional position data. Glenohumeral contact
      pressure and the area of impingement were compared between 20 degrees , 30
      degrees , and 40 degrees  of internal scapular rotation; between 20 degrees , 30
      degrees , and 40 degrees  of upward scapular rotation; and between 0 degrees  and
      10 degrees  of anterior scapular tilt. Data were analyzed with use of repeated
      measures analysis of variance with the Tukey post hoc test. RESULTS: Contact
      pressure was at its maximum in the posterior aspect of the glenohumeral joint.
      The glenohumeral contact pressure and internal impingement area increased with
      increasing internal scapular rotation. The glenohumeral contact pressure at 40
      degrees  of internal scapular rotation was significantly (43.4%) greater than
      that at 20 degrees  of internal scapular rotation (p < 0.01), and the impingement
      area at 40 degrees  of internal scapular rotation was significantly (43.1%)
      greater than that at 20 degrees  of internal scapular rotation (p < 0.05).
      Decreasing upward scapular rotation resulted in an increase in internal
      impingement area. The internal impingement area at 40 degrees  of upward motion
      was 38.1% less than that at 20 degrees  of upward rotation (p < 0.001) and 28.9%
      less than that at 30 degrees  of upward rotation (p < 0.01). CONCLUSIONS:
      Increasing internal scapular rotation and decreasing upward scapular rotation
      significantly increase glenohumeral contact pressure and the area of impingement
      of the rotator cuff tendon between the greater tuberosity and glenoid during
      simulated throwing motion.

PMID- 22992849
TI  - Talocalcaneal tarsal coalitions and the calcaneal lengthening osteotomy: the role
      of deformity correction.
AB  - BACKGROUND: Surgical resection of persistently painful talocalcaneal tarsal
      coalitions may not reliably relieve symptoms in patients with large coalitions
      associated with excessive hindfoot valgus deformity and subtalar posterior facet
      narrowing. Since 1991, calcaneal lengthening osteotomy, with or without coalition
      resection, has been used at our institution to relieve symptoms and to preserve
      motion at the talonavicular and calcaneocuboid joints. METHODS: We
      retrospectively reviewed the records for eight patients with thirteen painful
      talocalcaneal tarsal coalitions who had undergone a calcaneal lengthening
      osteotomy for deformity correction with or without coalition resection between
      1991 and 2005. Preoperative and postoperative clinical, radiographic, and
      computed tomographic records were reviewed. The duration of clinical follow-up
      ranged from two to fifteen years. RESULTS: Calcaneal lengthening osteotomy fully
      corrected the valgus deformity and provided short-to-intermediate term pain
      relief for the five patients (nine feet) in whom the talocalcaneal tarsal
      coalition was unresectable. The patient with resectable coalitions but excessive
      valgus deformities underwent calcaneal lengthening osteotomies along with
      coalition resections and had excellent deformity correction and pain relief in
      both feet. One of the two patients who underwent calcaneal lengthening osteotomy
      years after coalition resection had excellent correction and pain relief. The
      other patient had a coincident calcaneonavicular coalition and severe
      degenerative arthritis in the talonavicular joint. He underwent concurrent
      arthrodesis of the talonavicular joint and, although he had excellent deformity
      correction, had persistent pain. All feet underwent concurrent gastrocnemius or
      Achilles tendon lengthening. CONCLUSIONS: It is generally accepted that resection
      is the treatment of choice for an intractably painful small talocalcaneal tarsal
      coalition that is associated with a wide, healthy posterior facet and minimal
      valgus deformity of the hindfoot. Although triple arthrodesis has been
      recommended for those who do not meet all three criteria, the present study
      suggests that an algorithmic treatment approach is justified. Treatment of the
      valgus deformity appears to be as important as that of the coalition. Calcaneal
      lengthening osteotomy with gastrocnemius or Achilles tendon lengthening is
      effective for correcting deformity and relieving pain in rigid flatfeet, just as
      it is in flexible flatfeet.

PMID- 22992850
TI  - Mechanical comparison of novel bioabsorbable plates with titanium plates and
      small-series clinical comparisons for metacarpal fractures.
AB  - BACKGROUND: The use of bioabsorbable implants to negate the need for subsequent
      removal could offer major clinical advantages for the fixation of fractures. The
      aims of this study were to compare the mechanical properties of novel
      bioabsorbable plates with those of titanium plates in a fracture model and to
      demonstrate the clinical results of the use of these new plates for metacarpal
      fractures. METHODS: The first set of experiments compared the mechanical
      properties of bioabsorbable and titanium plates. Two types of bioabsorbable
      plates (one-third tubular and semi-tubular in cross-section) made of
      hydroxyapatite/poly-L-lactide and two types of titanium plates (for 1.5 and 2.0
      mm screws) were tested. Each plate was fixed on a polyether ether ketone (PEEK)
      rod, which was transversely cut at its midsection. The second part of the study
      compared the clinical results associated with the bioabsorbable and titanium
      plates that were used in sixteen nonrandomized consecutive patients with
      metacarpal fractures. RESULTS: The bending strength and stiffness of one-third
      tubular bioabsorbable plate constructs were comparable with those of titanium
      plates for 1.5-mm screws, and those of one-half tubular bioabsorbable plates were
      comparable with those of titanium plates for 2.0-mm screws. The mean torsional
      strength (and standard deviation) of the semi-tubular bioabsorbable plates (79.0
      +/- 7.9 N.cm) was significantly greater than that of titanium plates for 2.0 mm
      screws (56.7 +/- 4.0 N.cm) (p < 0.05). There were no significant differences in
      six-month postoperative clinical results between patients who received
      bioabsorbable plates and those who received titanium plates (total range of
      active motion, 267.0 degrees  +/- 6.0 degrees  compared with 250.0 degrees  +/-
      28.3 degrees ; grip strength, 92.7% +/- 19.7% compared with 86.4% +/- 28.6% of
      that on the contralateral side). CONCLUSIONS: The bending strength, stiffness,
      and torsional strength of novel one-third or semi-tubular bioabsorbable plates,
      when fixed on a PEEK rod, were comparable with those for titanium plates for 1.5
      or 2.0-mm screws. There were no significant differences in clinical results
      between these two types of plates in a small group of patients after short-term
      follow-up.

PMID- 22992851
TI  - The association between preoperative spinal cord rotation and postoperative C5
      nerve palsy.
AB  - BACKGROUND: C5 nerve palsy is a known complication of cervical spine surgery. The
      development and etiology of this complication are not completely understood. The
      purpose of the present study was to determine whether rotation of the cervical
      spinal cord predicts the development of a C5 palsy. METHODS: We performed a
      retrospective review of prospectively collected spine registry data as well as
      magnetic resonance images. We reviewed the records for 176 patients with
      degenerative disorders of the cervical spine who underwent anterior cervical
      decompression or corpectomy within the C4 to C6 levels. Our measurements included
      area for the spinal cord, space available for the cord, and rotation of the cord
      with respect to the vertebral body. RESULTS: There was a 6.8% prevalence of
      postoperative C5 nerve palsy as defined by deltoid motor strength of <= 3 of 5.
      The average rotation of the spinal cord (and standard deviation) was 2.8 degrees 
      +/- 3.0 degrees . A significant association was detected between the degree of
      rotation (0 degrees  to 5 degrees  versus 6 degrees  to 10 degrees  versus >= 11
      degrees ) and palsy (point-biserial correlation = 0.94; p < 0.001). A diagnostic
      criterion of 6 degrees  of rotation could identify patients who had a C5 palsy
      (sensitivity = 1.00 [95% confidence interval, 0.70 to 1.00], specificity = 0.97
      [95% confidence interval, 0.93 to 0.99], positive predictive value = 0.71 [95%
      confidence interval, 0.44 to 0.89], negative predictive value = 1.00 [95%
      confidence interval, 0.97 to 1.00]). CONCLUSIONS: Our evidence suggests that
      spinal cord rotation is a strong and significant predictor of C5 palsy
      postoperatively. Patients can be classified into three types, with Type 1
      representing mild rotation (0 degrees  to 5 degrees ), Type 2 representing
      moderate rotation (6 degrees  to 10 degrees ), and Type 3 representing severe
      rotation (>= 11 degrees ). The rate of C5 palsy was zero of 159 in the Type-1
      group, eight of thirteen in the Type-2 group, and four of four in the Type-3
      group. This information may be valuable for surgeons and patients considering
      anterior surgery in the C4 to C6 levels.

PMID- 22992852
TI  - Unconstrained shoulder arthroplasty for treatment of proximal humeral nonunions.
AB  - BACKGROUND: Unconstrained shoulder arthroplasty is one of several methods for
      treatment of proximal humeral fracture nonunions. The goal of this study was to
      define the results and complications of this procedure. METHODS: From 1976 to
      2007, sixty-seven patients underwent unconstrained shoulder arthroplasty for
      proximal humeral nonunion and were followed for more than two years. There were
      forty-nine women and eighteen men with a mean age of sixty-four years and a mean
      duration of follow-up of nine years (range, two to thirty years). The fracture
      type according to the Neer classification was two-part in thirty-six patients,
      three-part in sixteen, and four-part in fifteen. Hemiarthroplasty was performed
      in fifty-four patients and total shoulder arthroplasty was done in the remaining
      thirteen. RESULTS: There were thirty-three excellent or satisfactory results
      according to the modified Neer rating. Tuberosity healing about the prosthesis
      occurred in thirty-five shoulders. The mean pain score improved from 8.3
      preoperatively to 4.1 at the time of follow-up (p < 0.001). The average active
      shoulder elevation and external rotation improved from 46 degrees  and 26 degrees
      to 104 degrees  and 50 degrees  (p < 0.001). Shoulders with anatomic or nearly
      anatomic healing of the tuberosities had greater active elevation at the time of
      final follow-up (p = 0.02). There were fourteen complications in twelve patients,
      with twelve reoperations including five revisions. Kaplan-Meier survivorship with
      revision as the end point was 97% (95% confidence interval [CI]: 94.3, 100) at
      one year and 93% (95% CI: 88.0, 99.2) at five, ten, and twenty years.
      CONCLUSIONS: Shoulder arthroplasty decreases pain and improves function in
      patients with a proximal humeral nonunion. However, the overall results are
      satisfactory in less than half of the patients. Tuberosity healing is
      inconsistent and influences the functional outcome.

PMID- 22992853
TI  - Sports-related concussion: assessment and management.

PMID- 22992854
TI  - Clinical and structural results of arthroscopic repair of isolated subscapularis
      tear.
AB  - BACKGROUND: Even though the frequency of arthroscopic repair of isolated lesions
      of the subscapularis tendon has increased, few studies have presented clinical
      and anatomical outcomes of this treatment. We hypothesized that, after an
      arthroscopic repair, structural outcomes in the muscle have an influence on
      functional results. METHODS: A retrospective study was performed on twenty-two
      patients who had undergone arthroscopic repair of an isolated tear of the
      subscapularis tendon and had a mean follow-up of thirty-six months. Patients were
      evaluated preoperatively and postoperatively with use of the Constant-Murley
      score, a subjective shoulder value, the lift-off test, the belly-press test, and
      magnetic resonance imaging or computed tomography arthrography. The results were
      compared with those of a cohort of thirteen patients who underwent open repair of
      the subscapularis tendon tear. RESULTS: In the arthroscopic group, the Constant
      Murley score improved from a mean of 66 points preoperatively to a mean of 85
      points postoperatively (p < 0.05). The subscapularis tendon was healed in 86% of
      the patients. Three patients (14%) had a partial rupture limited to the superior
      tendon. Postoperatively, progression of fatty infiltration of the subscapularis
      muscle was observed in 55% of the patients. Ten patients (45%) had a severe but
      localized fatty infiltration area of the subscapularis muscle related to the
      larger tears. Subjective and functional outcomes were not influenced by tendon
      healing or postoperative fatty infiltration (p > 0.05). Clinical testing was
      significantly improved, but incomplete corrections remained frequent. Although
      open repair resulted in higher subjective shoulder scores and better strength
      scores, most other clinical parameters, postoperative subscapularis testing
      results, and structural outcomes were comparable between the arthroscopic repair
      and the open repair group. CONCLUSIONS: Arthroscopic repair of isolated
      subscapularis tears was associated with improved shoulder function and improved
      results on clinical testing. The tendon-healing rate was high but resulted in
      incomplete correction of the results of clinical testing. Progression of fatty
      infiltration in the subscapularis muscle was observed on magnetic resonance
      imaging but did not influence the clinical outcomes.

PMID- 22992855
TI  - Revision for unexplained pain following unicompartmental and total knee
      replacement.
AB  - BACKGROUND: Unicompartmental knee arthroplasty has been associated with
      consistently worse implant survival rates than total knee arthroplasty in
      worldwide arthroplasty registers. The rate of revision and the proportion of
      revisions performed for unexplained knee pain after either a unicompartmental or
      total knee arthroplasty were studied to assess if there is evidence to support
      the hypothesis that the numbers of revisions performed for unexplained knee pain
      differ between these two implant types. METHODS: Using data from the National
      Joint Registry (NJR) of England and Wales, we identified 402,714 primary knee
      arthroplasties (366,965 total knee arthroplasties and 35,749 unicompartmental
      knee arthroplasties) that were consecutively entered from April 2003 to December
      2010. The status of all implants was assessed as of December 2010, at which time
      6075 implants (4503 total knee implants and 1572 unicompartmental knee implants)
      had been revised at a maximum of eight years. Survival analysis and Cox
      regression analysis with adjustment of differences in age, sex, American Society
      of Anesthesiologists (ASA) grade, and indication for arthroplasty were performed
      with use of the end points of revision for any reason, revision for unexplained
      pain, and revision for other reasons. RESULTS: Revision for unexplained pain was
      more common after unicompartmental knee arthroplasty than after total knee
      arthroplasty (representing 23% of revisions as compared with 9% of revisions; p <
      0.001). The five-year rate of revision for unexplained pain was 1.6% for the
      unicompartmental knee arthroplasty group and 0.2% for the total knee arthroplasty
      group. With use of Cox regression, the hazard ratio (HR) for unicompartmental
      knee arthroplasty relative to total knee arthroplasty with the end points of
      revision for any reason, revision for unexplained pain, and revision for all
      other reasons were 2.82 (95% confidence interval [CI], 2.66 to 2.99; p < 0.001),
      6.76 (95% CI, 5.84 to 7.83; p < 0.001), and 2.39 (95% CI, 2.24 to 2.56; p <
      0.001), respectively. The mean time from primary implantation to revision was
      similar for both implant types. CONCLUSIONS: While more unicompartmental knee
      implants than total knee implants were revised for unexplained pain, when these
      revisions for unexplained pain were discounted, unicompartmental knee
      arthroplasty still had a significantly greater risk of revision from other
      reasons than did total knee arthroplasty. The revision rate in isolation may not
      be a reliable way to compare different implant designs and should instead be
      considered in the context of the reason for failure.

PMID- 22992856
TI  - Impact of total shoulder arthroplasty on generic and shoulder-specific health
      related quality-of-life measures: a systematic literature review and meta
      analysis.
AB  - BACKGROUND: Total shoulder arthroplasty is increasingly used in the treatment of
      arthritis. However, the effect of total shoulder arthroplasty on health-related
      quality of life has not been fully established. The goal of this systematic
      review and meta-analysis was to characterize the change in generic and shoulder
      specific health-related quality-of-life measures resulting from total shoulder
      arthroplasty. METHODS: We identified published studies reporting preoperative and
      postoperative health-related quality-of-life outcomes for patients receiving
      total shoulder arthroplasty. Health-related quality-of-life measures were
      identified, and meta-analysis was used to calculate standardized mean differences
      (SMDs, reflective of the effect size) and 95% confidence intervals for each
      scale. RESULTS: Twenty studies (1576 total shoulder replacements) met the
      inclusion criteria. Outcome measures were analyzed after an average postoperative
      follow-up duration of 3.7 +/- 2.2 years. The Short Form-36 demonstrated
      significant improvement in physical component summary scores (SMD = 0.7, p <
      0.001) but not in mental component summary scores (SMD = 0.2, p = 0.37).
      Significant improvements were observed in the visual analog scale score for pain
      (SMD = -2.5, p < 0.001) and scores on three shoulder-specific measures: the
      Constant score (SMD = 2.7, p < 0.001), American Shoulder and Elbow Surgeons score
      (SMD = 2.9, p < 0.001), and Simple Shoulder Test (SMD = 2.3, p < 0.001).
      CONCLUSIONS: Total shoulder arthroplasty leads to significant improvements in
      scores for function and pain. Shoulder-specific measures of function consistently
      showed the greatest degree of improvement, with large effect sizes. Total
      shoulder arthroplasty also leads to significant improvements in overall physical
      well-being, with a moderate-to-large effect size.

PMID- 22992857
TI  - Post-splinting radiographs of minimally displaced fractures: good medicine or
      medicolegal protection?
AB  - BACKGROUND: Many institutions perform radiographic documentation following splint
      application even when no manipulation had been performed. The purpose of this
      study was to evaluate the utility of post-splinting radiographs of acute non
      displaced or minimally displaced fractures that did not undergo manipulation. Our
      hypothesis was that post-splinting radiographs do not demonstrate changes in
      fracture alignment or impact the management of the patient. METHODS: After
      institutional review board exemption had been granted, consultations performed by
      orthopaedic residents at a level-I trauma center from September 2008 to April
      2010 were reviewed. Of 2862 consultations, 1321 involved acute fractures that
      were splinted. Radiographs revealed that 342 (25.9%) of the fractures were non
      displaced or minimally displaced and angulated (defined as <5 mm and <10 degrees
      , respectively) and 204 of them had been assessed with radiographs after
      splinting. Consults were reviewed to ensure that the patients had not undergone
      manipulation prior to or during splinting. Consult notes and radiographs obtained
      in the emergency room (ER), as well as follow-up radiographs, were reviewed to
      assess ultimate outcome. RESULTS: None of the 204 fractures (134 non-displaced
      and seventy minimally displaced) changed alignment following splinting. Two
      splints were reapplied, and the fractures sites were reimaged for undocumented
      reasons. Patients were subjected to an average of ten radiographs (range, four to
      twenty-five radiographs) of their extremities in the acute setting. On average,
      three post-splinting radiographs (range, one to ten radiographs) were obtained.
      The mean time between the initial and post-splinting radiographs was three hours
      and thirty minutes (range, nine minutes to twenty-four hours). The most common
      injury was a fracture about the hand or wrist. The 122 patients with that type of
      injury waited an average of almost three hours for an average of three post
      splinting radiographs, contributing to a total of nine radiographs performed
      acutely. ER visits tended to be longer for patients with post-splinting
      radiographs compared with those without them (p = 0.06). Follow-up radiographs
      were available for eighty-two patients. All fractures demonstrated maintained
      alignment. CONCLUSIONS: Post-splinting radiographs of non-displaced and minimally
      displaced fractures that do not undergo manipulation before or during
      immobilization are associated with longer ER waits, additional radiation
      exposure, and increased health-care costs without providing helpful information.
      While certain circumstances call for additional imaging, routine performance of
      post-splinting radiography of non-displaced or minimally displaced fractures
      should be discouraged.

PMID- 22992858
TI  - An orthopaedic case contributed substantially to the first malpractice crisis in
      the United States in the nineteenth century.

PMID- 22992859
TI  - The fate of manuscripts rejected by The Journal of Bone and Joint Surgery
      (American Volume).
AB  - BACKGROUND: Of the many manuscripts that are submitted to The Journal of Bone and
      Joint Surgery (American Volume) (JBJS-A) for publication, the majority are not
      accepted. However, little is known about the outcome of these rejected
      submissions. To determine the fate of studies rejected by JBJS-A, we conducted a
      follow-up investigation of all clinical and basic science manuscripts that were
      submitted to The Journal between January 2004 and June 2005 but were not
      accepted. METHODS: For each rejected manuscript, data were extracted on a wide
      variety of scientific and nonscientific characteristics, which were plausibly
      related to subsequent publication. PubMed searches were conducted to determine
      which manuscripts achieved full publication within five years, and logistic
      regression was used to identify the factors associated with publication. To
      further elucidate the factors associated with publication, a survey was
      administered to the corresponding author of each rejected manuscript. RESULTS: At
      five years following rejection by JBJS-A, 75.8% (696 of 918) of manuscripts had
      reached full publication. In the multivariate analysis, factors associated with a
      higher likelihood of subsequent publication included grade of initial review by
      JBJS-A (p = 0.029), disclosure of a for-profit or nonprofit conflict of interest
      (p = 0.028 and 0.027, respectively), and a greater number of prior publications
      in frequently cited orthopaedic journals by the corresponding author (p <
      0.0001). Manuscripts were less likely to reach full publication if the
      corresponding author was from Asia or the Middle East (p = 0.004) or was a woman
      (p = 0.003). Among survey respondents who indicated that their study had not yet
      reached full publication, the most commonly cited reason was lack of time
      (reported by 51.4% of respondents [thirty-eight of seventy-four]). CONCLUSIONS:
      Most manuscripts (75.8%) not accepted by JBJS-A were published elsewhere within
      five years of rejection. The factors predictive of subsequent publication were
      primarily investigator-related as opposed to study-related. Given this low
      threshold for eventual publication, readers are encouraged to use criteria other
      than inclusion in the PubMed database to identify high-quality papers.

PMID- 22992860
TI  - Resident duty-hour restrictions-who are we protecting?: AOA critical issues.
AB  - As advocated by Nasca, our teaching programs must nurture professionalism and the
      effacement of self interest that is the core of the practice of medicine and the
      profession. The evidence to date suggests that work-hour restrictions based
      solely on clock-defined time limits discourage, rather than promote, the
      professional behavior that we desire in tomorrow's physicians. Notwithstanding
      any issues related to duty hours or fitness for duty, a competency-based system
      of medical education is both desirable and necessary in the current environment
      of medical education. In the absence of evidence to suggest that duty-hour limits
      reduce medical errors and enhance patient safety, and until we have evolved to a
      competency-based system of resident education, a misguided and overzealous focus
      on limiting work hours should not be allowed to exert the unintended consequence
      of eroding the ethos of professionalism that we, and our patients, have come to
      expect of a physician.

PMID- 22992861
TI  - Learning and retaining simulated arthroscopic meniscal repair skills.
AB  - BACKGROUND: Previous studies of task-specific skills have suggested that a loss
      of technical performance occurs if the skill is not practiced for a six-month
      period. The aims of this study were to objectively demonstrate the learning curve
      for a complex arthroscopic task (meniscal repair) by means of motion analysis and
      to determine the impact of task repetition on the retention of this skill.
      METHODS: Nineteen orthopaedic residents with experience in routine knee
      arthroscopy but not in arthroscopic meniscal repair were recruited into a
      randomized study. During the initial learning phase, all subjects performed
      twelve meniscal repairs on a knee simulator over a three-week period. A validated
      motion analysis tracking system was used to objectively record the performance
      and learning of each subject; the outcomes were the time taken, distance
      traveled, and number of hand movements. The subjects were then randomized into
      three groups. Group A performed one meniscal repair each month, Group B performed
      one meniscal repair at three months, and Group C performed no repairs during this
      interim phase. All three groups then returned at the six-month point for the
      final assessment phase, during which they carried out an additional twelve
      meniscal repairs over three weeks. RESULTS: All subjects demonstrated a clear
      learning curve during the initial learning phase, with significant objective
      improvement in all motion analysis parameters over the initial twelve episodes (p
      < 0.0001). Although some residents had reached a learning plateau by twelve
      episodes, others continued to make further improvements for up to another nine
      episodes. Importantly, Group C did not display any loss of skill between the
      initial learning phase and final evaluation phase despite a six-month break in
      task repetition (p > 0.05). CONCLUSIONS: In contrast to previous studies,
      residents did not lose any skill over a six-month interruption in task
      performance, and other residents took longer to produce a more consistent
      performance.

PMID- 22992862
TI  - C677T methylenetetrahydrofolate reductase gene polymorphism as a risk factor
      involved in venous thromboembolism: a population-based case-control study.
AB  - The aim of the current study was to investigate the possible correlation between
      the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism and venous
      thromboembolism (VTE) in a population-based case-control study. Homocysteine
      (Hcy) was quantified by Abbott IMx immunoassay; screening for C677T MTHFR
      substitution was performed by polymerase chain reaction (PCR) and restriction
      analysis. The results from the two groups (440 patients and 440 controls)
      revealed that the frequency of T alleles and TT carriers was significantly higher
      in patients compared with that of the healthy controls. The plasma levels of Hcy
      in the VTE group (13.05+/-2.37 umol/l) were significantly higher compared with
      those in the control group (11.94+/-2.03 umol/l, P<0.001). The C677T MTHFR
      polymorphism is suggested to be associated with the risk for VTE. Plasma levels
      of Hcy were raised in individuals with the homozygous MTHFR 677TT genotype. In
      conclusion, the results of the current study suggest that hyperhomocysteinemia
      and the homozygous 677TT MTHFR genotype are risk factors for VTE.

PMID- 22992863
TI  - Coxsackievirus and adenovirus receptor promotes antitumor activity of oncolytic
      adenovirus H101 in esophageal cancer.
AB  - Esophageal cancer is an intractable disease due to late diagnosis, high incidence
      of post-surgical locoregional recurrence and frequent distant metastasis.
      Oncolytic adenovirus (Ad) vectors are a promising method for cancer treatment.
      The H101 virus is a recombinant Ad which has replication-selective properties and
      replicates only in tumor cells. The coxsackievirus and adenovirus receptor (CAR)
      is considered a surrogate marker that monitors the outcome of Ad-mediated gene
      therapy. Accumulating evidence indicates that CAR expression levels are lower in
      various types of tumors such as ovarian, lung, breast and bladder when compared
      to their normal counterparts. In this study, we reported that trichostatin A
      (TSA) induced the expression of CAR in esophageal squamous cell carcinoma (ESCC)
      cell lines through the MAPK/ERK1/2 signaling pathway. The expression levels of
      CAR were positively related with the antitumor activity of H101. Our results
      suggest that TSA increases the antitumor activity of the oncolytic adenovirus
      H101 through the MAPK/ERK pathway.

PMID- 22992864
TI  - Rural and small town breast cancer survivors' preferences for physical activity.
AB  - BACKGROUND: Recent data suggests that only 35 % of rural and small town breast
      cancer survivors are achieving physical activity (PA) guidelines after treatment.
      PURPOSE: The purpose of this study was to determine preferences for PA counseling
      and programming and barriers to program participation in a sample of rural and
      small town breast cancer survivors. METHODS: Survivors (n = 524) residing in
      rural and small town areas of Alberta, Canada completed a mailed self-report
      survey that assessed demographic variables, PA, and PA counseling and programming
      preferences. RESULTS: Seventy-eight percent of survivors indicated they would
      have possibly (i.e., yes or maybe) been interested in being counseled about PA at
      the time of diagnosis, while 70 % would possibly be interested in being counseled
      about PA at this current time. Overall, 85 % felt they would possibly be able to
      participate in a PA program. Receiving chemotherapy was negatively associated
      with wanting to receive PA counseling (odds ratio [OR] = 0.58; 95 % confidence
      interval [CI], 0.39 to 0.86), PA program interest (OR = 0.43; 95 % CI, 0.28 to
      0.67), and PA program ability (OR = 0.44; 95 % CI, 0.26 to 0.75). Preferred
      activities involved walking (51 %), flexibility and related activities (e.g.,
      yoga, stretching) (36 %), and strength training (27 %). CONCLUSIONS: Rural and
      small town survivors appear to be interested in and able to participate in PA
      counseling and programs. PA initiatives targeted to the preferences of breast
      cancer survivors living in nonurban areas may be more likely to facilitate and
      maintain PA behavior.

PMID- 22992865
TI  - ACR-AAPM-SIIM practice guideline for determinants of image quality in digital
      mammography.

PMID- 22992866
TI  - ACR-AAPM-SIIM technical standard for electronic practice of medical imaging.

PMID- 22992867
TI  - ACR-AAPM-SIIM practice guideline for digital radiography.

PMID- 22992868
TI  - ACR-AAPM-SIIM practice guidelines.

PMID- 22992869
TI  - Surgical technique: vastus medialis and vastus lateralis as flap transfer for
      knee extensor mechanism deficiency.
AB  - BACKGROUND: Loss of the quadriceps tendon, patella, and patellar tendon leaves a
      major anterior defect that is difficult to close and compromises knee extension
      strength. Gastrocnemius muscle transfer does not sufficiently cover such major
      defects. This paper describes a new surgical technique that addresses these
      defects and the results of eight cases of revision TKA managed with this new
      technique. DESCRIPTION OF TECHNIQUE: The new procedure transfers the vastus
      medialis or the vastus lateralis and their tibial attachments or both muscles and
      their distal expansions combined with gastrocnemius and soleus flaps to cover
      major deficiencies in the anterior knee. Nine cadaver knee specimens were
      dissected to determine the effect of the transfer on nerve and blood supply of
      the muscles. METHODS: Eight patients underwent the new procedure between 2005 and
      2009. Four knees had vastus medialis transfer, two vastus medialis and vastus
      lateralis transfer, two vastus medialis and medial gastrocnemius transfer, and
      two medial gastrocnemius and medial 1/2 of the soleus muscle transfer. Minimum
      followup was 15 months (mean, 43 months; range, 15-74 months). Patients were
      evaluated for anterior knee pain, quality of knee closure, ROM, extensor lag,
      walking ability, use of assistive devices, and ability to climb stairs with the
      operated extremity. RESULTS: All patients achieved closure of the knee without
      synovial leaks by 10 days postoperatively. Mean flexion contracture at last
      followup was 3 degrees  (range, 0 degrees -7 degrees ). Mean extension lag was 22
      degrees  (range, 5 degrees -65 degrees ). Extension lag was less in those knees
      that included gastrocnemius or soleus muscle transfer. None of the flaps
      developed necrosis. CONCLUSIONS: The vastus medialis and vastus lateralis muscles
      provide adequate coverage for anterior soft tissue deficits of the knee.

PMID- 22992870
TI  - Intraoperative cartilage degeneration predicts outcome 12 months after hip
      arthroscopy.
AB  - BACKGROUND: When considering arthroscopic surgery for treatment of hip pain, it
      is important to understand the influence of joint degeneration on the likelihood
      of success. Previous research has shown poorer outcomes among patients with
      osteoarthritis but new arthroscopic techniques including femoroacetabular
      impingement correction and microfracture may lead to better arthroscopic
      outcomes. QUESTIONS/PURPOSES: We investigated the effect of intraarthroscopic
      articular and rim cartilage degeneration on the outcome after hip arthroscopy
      using contemporary techniques. METHODS: The modified Harris hip score (MHHS) and
      nonarthritic hip score (NAHS) were completed preoperatively and 12 months
      postoperatively by 560 patients undergoing hip arthroscopy after March 2007.
      Change in these scores was compared between patients with and without acetabular
      or femoral articular cartilage degeneration and between patients with and without
      rim cartilage degeneration. Correlation and regression analyses were used to
      predict the change in outcome scores based on the severity of cartilage
      degeneration. RESULTS: Hips without degeneration had greater improvement in the
      outcome scores. The presence of cartilage degeneration showed negative
      correlations with change in outcomes. The best model to explain change in MHHS
      included preoperative score, articular cartilage degeneration grade, and rim
      lesion grade (adjusted R(2) = 0.24). CONCLUSIONS: Our data support previous
      findings regarding the negative influence of cartilage degeneration on
      improvement after hip arthroscopy. Nevertheless, many patients with cartilage
      degeneration still improved and the severity of degeneration accounts for little
      of the resulting variance in change. Future studies must determine the clinical
      importance of the improvements gained by patients with cartilage degeneration and
      identify other predictors of outcome. LEVEL OF EVIDENCE: Level III, prognostic
      study. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 22992871
TI  - 2011 International Hip Society: editorial comment.

PMID- 22992872
TI  - HIV risks associated with patronizing alcohol serving establishments in South
      African Townships, Cape Town.
AB  - Alcohol use has been closely linked with HIV risk behaviors in South Africa. The
      places where people drink are often the same settings in which they meet new sex
      partners and may contribute independently to sexual risk. This current study
      examines the independent effects of patronizing alcohol serving establishments
      (shebeens) and alcohol use in predicting HIV risk behaviors. Men (n = 981) and
      women (n = 492) were recruited from inside shebeens and surrounding areas
      proximal to shebeens in eight separate neighborhoods in a Township in Cape Town,
      South Africa. Anonymous community surveys measured demographic characteristics,
      alcohol use, shebeen attendance, and sexual risk behaviors. Comparisons of 1210
      (82 %) participants who patronized shebeens in the past month with 263 (18 %)
      participants who did not patronize shebeens demonstrated higher rates of alcohol
      use frequency and quantity, more sexual partners, and higher rates of vaginal
      intercourse without condoms for the patrons. Multiple linear regression analysis
      found shebeen attendance in the past month predicted greater sexual risk for HIV
      beyond demographic characteristics and alcohol use. Social influences and
      environmental factors in shebeens could be contributing to sexual risk behavior
      independently of alcohol consumption. Further research is needed to understand
      the environmental factors of shebeens that promote and influence HIV risk
      behaviors.

PMID- 22992873
TI  - Pretreatment PET in breast cancer: is there a role?

PMID- 22992874
TI  - [A windy affair...].

PMID- 22992875
TI  - Significance of stromal decorin expression during the progression of breast
      cancer.
AB  - Decorin, a small leucine-rich proteoglycan and important component of the
      extracellular matrix (ECM), is a natural anticancer agent that modulates several
      receptors involved in cell growth and survival. Reductions in decorin expression
      may weaken the ECM and enhance the effectiveness of these receptors and may,
      consequently, lead to tumor spreading. To determine the contribution of stromal
      decorin regulation in the development of breast cancer and in tumor invasiveness,
      immunohistochemistry was used to examine the expression of stromal decorin in 120
      breast cancer tissue samples. In patients with invasive breast carcinoma (IBC),
      stromal decorin expression was highest in normal gland tissue, lower in in situ
      components and the lowest in invasive components. Stromal decorin expression
      adjacent to malignant cells in IBC tumors was also significantly weaker compared
      to that in pure ductal carcinoma in situ (DCIS). These findings indicate that
      there is a striking difference in the stromal decorin expression around normal
      glands and around DCIS or IBC tumors. Reduced levels of decorin were associated
      with more aggressive disease; this finding was consistent with the view that
      reduced decorin expression may facilitate tumorigenesis, tumor invasion and/or
      tumor growth. Given these and other reported findings, evaluating stromal decorin
      expression may be useful in assessing prognosis and malignant potential;
      therefore, a large-scale study of decorin expression is warranted.

PMID- 22992877
TI  - Discrepancies between frozen and paraffin tissue sections have little effect on
      outcome of staged total knee arthroplasty revision for infection.
AB  - BACKGROUND: Intraoperative analysis of frozen tissue samples has been used to
      diagnose periprosthetic joint infection in revision total knee arthroplasty, but
      the precision and reliability of this test throughout staged revision
      arthroplasty have not been well characterized. We undertook this study to
      determine the rate of discrepancy between frozen and permanent histopathologic
      samples in the diagnosis of periprosthetic infection at both the index total knee
      arthroplasty revision procedure and the attempted reimplantation. METHODS:
      Seventy-six patients who underwent staged revision of a total knee arthroplasty
      for apparent infection had samples for frozen and permanent sections obtained at
      both the index revision procedure and subsequent reimplantation attempts. We
      investigated the rate of discrepancy between these frozen and permanent sections.
      The clinical and radiographic outcomes of patients with and without concordance
      between the frozen and permanent sections were reviewed. RESULTS: Concordance was
      noted between 297 (97.7%) of the 304 frozen sections and the permanent sections.
      Seven discrepancies between diagnoses based on frozen and permanent sections were
      noted; however, additional samples in these patients were positive and management
      was not affected. Fewer discrepancies were found during the initial revision
      procedure (one of 92, 1%) compared with reimplantation (six of 212, 3%). The mean
      time to reimplantation was similar between patients with and without a
      discrepancy in diagnosis between the frozen and permanent sections (185 compared
      with 157 days). The rate of discrepancy between frozen and permanent
      histopathologic sections was low, and no discrepancy affected the final outcome
      of any patient. CONCLUSIONS: The rate of discrepancy between frozen and permanent
      histopathologic samples was low for both index revision and reimplantation
      procedures. In rare instances of discrepancy, management should be unaffected
      provided a sufficient number of samples were collected.

PMID- 22992879
TI  - Cementless total hip arthroplasty with the rectangular titanium Zweymuller stem:
      a concise follow-up, at a minimum of twenty years, of previous reports.
AB  - In 2002 and 2006, we reported the long-term results of 208 total hip replacements
      performed with the Zweymuller stem and a threaded cup in 200 patients. The
      present study gives an update on this patient cohort. At a minimum of twenty
      years postoperatively, seventy-three patients (seventy-five hips) were available
      for follow-up; twelve patients were lost to follow-up. The key findings of our
      previous reports were the absence of aseptic femoral stem loosening and a poor
      rate of survival of the threaded cup. Since then, two revisions have been
      performed because of aseptic stem loosening. We observed osteolytic lesions
      around the proximal part of the femoral component on twenty-four (47%) of fifty
      one radiographs, but no stem was deemed at risk for loosening. The probability of
      survival of the stem at twenty years was 0.96 (95% confidence interval, 0.91 to
      0.99), and the probability of survival of the cup at twenty years was 0.67 (95%
      confidence interval, 0.57 to 0.75). The Zweymuller femoral stem, a tapered,
      rectangular implant, continues to give excellent long-term results.

PMID- 22992878
TI  - Sclerostin antibody increases bone volume and enhances implant fixation in a rat
      model.
AB  - BACKGROUND: Previous studies have demonstrated that sclerostin blockade is
      anabolic for bone. This study examined whether systemic administration of
      sclerostin antibody would increase implant fixation and peri-implant bone volume
      in a rat model. METHODS: Titanium cylinders were placed in the femoral medullary
      canal of ninety male Sprague-Dawley rats. One-half of the rats (n=45) received
      murine sclerostin antibody (Scl-Ab, 25 mg/kg, twice weekly) and the other one
      half (n=45) received saline solution. Equal numbers of rats from both groups were
      sacrificed at two, four, or eight weeks after the implant surgery and the femora
      were examined by microcomputed tomography, mechanical pull-out testing, and
      histology. RESULTS: Fixation strength in the two groups was similar at two weeks
      but was 1.9-fold greater at four weeks (p=0.024) and 2.2-fold greater at eight
      weeks (p<0.001) in the rats treated with sclerostin antibody. At two weeks,
      antibody treatment led to increased cortical area, with later increases in
      cortical thickness and total cross-sectional area. Significant differences in
      peri-implant trabecular bone were not evident until eight weeks but included
      increased bone volume per total volume, bone structure that was more plate-like,
      and increased trabecular thickness and number. Changes in bone architecture in
      the intact contralateral femur tended to precede the peri-implant changes. The
      peri-implant bone properties accounted for 61% of the variance in implant
      fixation strength, 32% of the variance in stiffness, and 63% of the variance in
      energy to failure. The implant fixation strength at four weeks was approximately
      equivalent to the strength in the control group at eight weeks. CONCLUSIONS:
      Sclerostin antibody treatment accelerated and enhanced mechanical fixation of
      medullary implants in a rat model by increasing both cortical and trabecular bone
      volume.

PMID- 22992880
TI  - Utility of intraoperative frozen section histopathology in the diagnosis of
      periprosthetic joint infection: a systematic review and meta-analysis.
AB  - BACKGROUND: The accuracy of intraoperative periprosthetic frozen section
      histologic evaluation in predicting a diagnosis of periprosthetic joint infection
      prior to microbiologic culture results is unknown. METHODS: We performed a
      systematic review and meta-analysis of all longitudinal studies that compared
      frozen section histologic results with simultaneously obtained microbiologic
      culture at the time of revision total hip or total knee arthroplasty. The data
      sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science,
      and SCOPUS, from the inception of each database to January 2010. RESULTS: Twenty
      six studies involving 3269 patients undergoing revision hip or knee arthroplasty
      met the inclusion criteria. A culture-positive periprosthetic joint infection was
      confirmed in 796 (24.3%) of the patients. Frozen section results, using any of
      the diagnostic criteria chosen by the investigating pathologist, had a pooled
      diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a
      likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a
      likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the
      diagnosis of periprosthetic joint infection. Fifteen studies utilizing a
      threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to
      define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI,
      23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per
      high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0).
      There was no significant difference between the diagnostic odds ratio or
      likelihood ratios associated with these thresholds. The moderate to high
      heterogeneity among the included studies was unexplained by variability in the
      study design, diagnostic criteria for acute inflammation, reference standard for
      periprosthetic joint infection, or prevalence of infection. This heterogeneity
      could be due to differences in the inclusion and exclusion criteria, tissue
      sampling error, experience or technique of the pathologists, number of
      microscopic fields visualized, and field diameter examined. CONCLUSIONS:
      Intraoperative frozen sections of periprosthetic tissues performed well in
      predicting a diagnosis of culture-positive periprosthetic joint infection but had
      moderate accuracy in ruling out this diagnosis. Frozen section histopathology
      should therefore be considered a valuable part of the diagnostic work-up for
      patients undergoing revision arthroplasty, especially when the potential for
      infection remains after a thorough preoperative evaluation. The optimum
      diagnostic threshold (number of PMNs per high-power field) required to
      distinguish periprosthetic joint infection from aseptic failure could not be
      discerned from the included studies. There was no significant difference between
      the diagnostic accuracy of frozen section histopathology utilizing the most
      common thresholds of five or ten PMNs per high-power field.

PMID- 22992881
TI  - Patellofemoral arthroplasty: the other unicompartmental knee replacement.
AB  - Patellofemoral arthritis is a relatively common condition, affecting up to 24% of
      women and 11% of men over the age of fifty-five years who have symptomatic
      osteoarthritis of the knee. Isolated patellofemoral arthritis is not as prevalent
      and has been reported to occur in 9% of radiographs of symptomatic knees in
      individuals over the age of forty years. Approximately 75% of all patellofemoral
      arthroplasties are done in women, and the increased frequency of patellofemoral
      disease may be related to the frequency of knee malalignment and dysplasia in
      women, although some studies have noted no sex-specific differences in knee
      kinematics.

PMID- 22992882
TI  - What's new in total hip arthroplasty.

PMID- 22992883
TI  - Spinal column injuries among Americans in the global war on terrorism.
AB  - BACKGROUND: While combat spinal injuries have been documented since the fourth
      century BC, a comprehensive analysis of such injuries has not been performed for
      any American military conflict. Recent literature has suggested that spinal
      injuries account for substantial disability in wounded service members. METHODS:
      The Joint Theater Trauma Registry was queried to identify all American military
      personnel who sustained injuries to the back, spinal column, and/or spinal cord
      in Iraq or Afghanistan from October 2001 to December 2009. Spinal injuries were
      categorized according to anatomic location, neurological involvement, mechanism
      of injury, and concomitant wounds. RESULTS: Of 10,979 evacuated combat
      casualties, 598 (5.45%) sustained 2101 spinal injuries. Explosions accounted for
      56% of spinal injuries, motor vehicle collisions for 29%, and gunshots for 15%.
      Ninety-two percent of all injuries were fractures, with transverse process,
      compression, and burst fractures the most common. Spinal cord injuries were
      present in 17% (104) of the 598 patients. Concomitant injuries frequently
      occurred in the abdomen, chest, head, and face. CONCLUSIONS: The incidence of
      spine trauma sustained by military personnel in Iraq and Afghanistan is higher
      than that reported for previous conflicts, and the nature of these injuries may
      be similar to those in severely injured civilians. Further research into optimal
      management and rehabilitation is critical for military service members and
      severely injured civilians with spine trauma.

PMID- 22992884
TI  - Quantification of humeral head deformity following neonatal brachial plexus
      palsy.
AB  - BACKGROUND: Neonatal brachial plexus palsy frequently leads to glenohumeral
      dysplasia if neurological recovery is incomplete. Although glenoid retroversion
      and glenohumeral subluxation have been well characterized, humeral head deformity
      has not previously been quantified. Nonetheless, humeral head flattening is
      described as a contraindication to joint contracture release and external
      rotation tendon transfers. This study describes a novel technique for objectively
      quantifying humeral head deformity with use of magnetic resonance (MR) imaging
      and correlates the humeral head deformity with clinical and radiographic outcomes
      following joint rebalancing surgery. METHODS: Magnetic resonance images of thirty
      two children (age, 0.7 to 11.5 years) with neonatal brachial plexus palsy were
      retrospectively reviewed. Passive shoulder external rotation and Mallet scores
      were reviewed before joint rebalancing surgery and at a minimum clinical follow
      up interval of two years. The humeral head skewness ratio on preoperative and
      postoperative axial MR images was defined as the ratio of anterior to posterior
      humeral head area, and this ratio was compared between affected and unaffected
      shoulders and with the glenoid version angle, posterior subluxation of the
      humeral head, and clinical parameters before and after surgery with use of paired
      t tests and Spearman correlation. Intraobserver and interobserver reliability of
      MR image measurements was determined. RESULTS: Measurements of the skewness ratio
      on the affected side had moderate to substantial intraobserver reliability (0.53
      to 0.72) and substantial interobserver reliability (0.65 to 0.71).
      Preoperatively, the skewness ratio of the affected humeral head (mean, 0.76;
      range, 0.54 to 1.03) differed significantly from the ratio in the contralateral
      shoulder (p<0.05) and was significantly associated with the glenoid version angle
      (p<0.05) and posterior subluxation of the humeral head (p<0.05). Remodeling of
      the affected humeral head was observed postoperatively, with a significant
      improvement in the skewness ratio (p<0.05). However, there were no significant
      correlations between the preoperative skewness ratio and postoperative clinical
      outcomes. CONCLUSIONS: Humeral head deformity in neonatal brachial plexus palsy
      correlated with other measures of glenohumeral dysplasia and could be reliably
      and objectively quantified on MR imaging with use of the skewness ratio. The
      humeral head deformity can remodel following joint rebalancing surgery, and such
      a deformity alone does not preclude a successful outcome after surgical attempts
      to restore glenohumeral congruity.

PMID- 22992885
TI  - Preclinical computational models: predictors of tibial insert damage patterns in
      total knee arthroplasty: AAOS exhibit selection.
AB  - Computational models that predict clinical surface damage of the tibial insert
      during activities of daily living are emerging as powerful tools to assess the
      safety and efficacy of contemporary total knee arthroplasty designs. These models
      have the advantage of quickly determining the performance of new designs at low
      cost, and they allow direct comparison with the performance of classic,
      clinically successful designs. This study validated finite element and kinematic
      modeling predictions through comparison with preclinical physical testing
      results, damage patterns on retrieved tibial inserts, and clinically measured
      knee motion. There is a mounting body of evidence to support the role of
      computational modeling as a preclinical tool that enables the optimization of
      total knee arthroplasty designs and the auditing of component quality control
      before large-scale manufacturing is undertaken.

PMID- 22992886
TI  - Chromogranin A cell density in the rectum of patients with irritable bowel
      syndrome.
AB  - In a previous study, chromogranin A (CgA) cell density in the colon of patients
      with irritable bowel syndrome (IBS) was found to be reduced. It has been
      suggested that intestinal CgA cell density may be used as a marker for the
      diagnosis of IBS. The rectum harbours a larger number of large intestinal
      endocrine cells and is more accessible for biopsies than the colon. The present
      study aimed at determining the CgA cell density in the rectum of IBS patients. A
      total of 47 patients with IBS that fulfilled the Rome Criteria III (39 females
      and 8 males; average age, 38 years) were included. A total of 28 patients had
      diarrhea (IBS-D) and 19 had constipation (IBS-C) as the predominant symptom. A
      total of 27 subjects that underwent colonoscopy with rectal biopsies were used as
      the controls. These subjects underwent colonoscopy due to gastrointestinal
      bleeding (the source of which was identified as haemorrhoids or angiodysplasia;
      19 females and 8 males; average age, 49 years), or health worries. The rectal
      biopsies were immunostained for CgA and quantified by computer image analysis.
      The CgA density in the controls was 206.3+/-22.2 (mean +/- SEM), in all IBS
      patients 190.2+/-14.3, in IBS-D patients 188.8+/-14.7 and in IBS-C patients
      195.3+/-34.1. There was no statistically significant difference between the
      controls, IBS, IBS-D or IBS-C patients (P=0.5, 0.5 and 0.7, respectively). The
      present study showed that although the rectum comprises the same endocrine cell
      types as the colon, attention must be paid when drawing conclusions regarding the
      whole large intestine from studies carried out on the rectum. This particularly
      applies when endocrine cells are investigated. As CgA cell density represents the
      total endocrine cell content of the rectum, changes in specific endocrine cells
      in IBS patients cannot be excluded.

PMID- 22992887
TI  - Hexane extract from Uncaria sinensis exhibits anti-apoptotic properties against
      glutamate-induced neurotoxicity in primary cultured cortical neurons.
AB  - We explored the neuroprotective effects of a hexane extract from Uncaria sinensis
      (HEUS) against glutamate-induced toxicity focusing on its anti-apoptotic
      mechanism in primary cultured cortical neurons. Pretreatment with HEUS resulted
      in significantly reduced glutamate-induced toxicity in a dose-dependent manner
      with a decrease in the release of lactate dehydrogenase. Morphological assay and
      flow cytometry were performed for determination of the type of cell death;
      according to the results, treatment with HEUS resulted in a significant reduction
      of glutamate-induced apoptotic cell death. We examined the anti-apoptotic
      mechanism of HEUS; treatment with HEUS resulted in markedly decreased expression
      of death receptor (DR)4, which was induced by glutamate stimulation. In contrast,
      treatment with HEUS resulted in significantly enhanced levels of expression of
      glutamate-attenuated XIAP and Bcl-2, as well as marked blockade of glutamate
      induced Bid cleavage, which inhibits both extrinsic and intrinsic apoptosis
      pathways. In addition, pretreatment with HEUS resulted in almost complete
      blockade of glutamate-induced activation of caspases-8, -9 and -3, as well as
      cleavage of poly (ADP-ribose) polymerase. These findings suggest that the
      neuroprotective effects of HEUS against glutamate-induced toxicity occur via
      inhibition of DR4 and expression of anti-apoptotic proteins XIAP and Bcl-2
      resulting in effective abrogation of the activation of caspase cascades and
      promotion of cell survival.

PMID- 22992888
TI  - Supercritical fluid extraction of phenolic compounds and antioxidants from grape
      (Vitis labrusca B.) seeds.
AB  - Supercritical fluid extraction (SFE) technique was applied and optimized for
      temperature, CO2 pressure and ethanol (modifier) concentration using orthogonal
      array design and response surface methodology for the extract yield, total
      phenols and antioxidants from grape (Vitis labrusca B.) seeds. Effects of
      extraction temperature and pressure were found to be significant for all these
      response variables in SFE process. Optimum SFE conditions (44 ~ 46  degrees C
      temperature and 153 ~ 161 bar CO2 pressure) along with ethanol (<7 %) as
      modifier, for the maximum predicted values of extract yield (12.09 %), total
      phenols (2.41 mg GAE/ml) and antioxidants (7.08 mg AAE/ml), were used to obtain
      extracts from grape seeds. The predicted values matched well with the
      experimental values (12.32 % extract yield, 2.45 mg GAE/ml total phenols and 7.08
      mg AAE/ml antioxidants) obtained at optimum SFE conditions. The antiradical assay
      showed that SFE extracts of grape seeds can scavenge more than 85 % of 1, 1
      diphenyl-2-picrylhydrazyl (DPPH) radicals. The grape seeds extracts were also
      analyzed for hydroxybenzoic acids which included gallic acid (1.21 ~ 3.84
      MUg/ml), protocatechuic acid (3.57 ~ 11.78 MUg/ml) and p-hydroxybenzoic acid
      (206.72 ~ 688.18 MUg/ml).

PMID- 22992889
TI  - Ghrelin: a new treatment for non-alcoholic fatty liver disease?

PMID- 22992890
TI  - [Huge retrovesical tumor as an incidental finding: desmoid-type fibromatosis: a
      case report].
AB  - We report the case of a 57-year-old patient with a huge, retrovesical, aggressive
      desmoid fibromatosis detected incidentally during preoperative staging for
      radical prostatectomy. The tumor was locally invasive consisting of monoclonal
      and fibroblastic proliferations. The etiology of such tumors is not well known
      but they are mostly sporadic and aggressive fibromatosis is sometimes associated
      with familial adenomatous polyposis (FAP) or Gardner's syndrome. Such desmoid
      tumors are slow growing and locally invasive but lack metastatic potential.
      Complete resection with wide margins is the therapy of choice and the tendency to
      recur is high. Radiotherapy following surgery is controversial. We discuss the
      pathogenesis, clinical manifestations and therapy of such rare tumors.

PMID- 22992891
TI  - [Highlights of the history of onanism].
AB  - For many societies in the world onanism is taboo because of religious and medical
      ethics. From ancient times until the present day this type of body sensation is
      disclaimed by modern communities like a recurrent theme. After the discovery of
      the mechanism of fertilisation by the biologist Eduard van Beneden (1846-1910) in
      1875 the feminine clitoris was declared to be a dispensable organ. The clitoris
      was suspected of causing hysteria, epilepsy and other forms of insanity. In the
      eighteenth century masturbation performed by young men was classified as a
      consumptive disease that caused inevitable death. The following presentation
      gives an historical overview through the history of onanism that demonstrates the
      artistic, philosophical and medical point of view on the sexuality of men.

PMID- 22992892
TI  - Has the role of tibial interlocking nailing in closed tibial-shaft fractures
      diminished?

PMID- 22992893
TI  - Healthiness of survival and quality of death among oldest old in China using
      fuzzy sets.
AB  - OBJECTIVE: To investigate healthiness of survival and quality of death among
      oldest-old Chinese. METHODS: Grade of Membership (GoM) method is applied to
      fulfill our goals using a nationwide longitudinal survey in China. RESULTS: GoM
      method generates six pure types/profiles for healthiness of survival and five
      profiles/types for quality of death. The authors combine these 11 profiles into 4
      groups. On average, a Chinese oldest old from 1998 to 2000 had 48% probability of
      experiencing healthy survival, with 30% experiencing unhealthy survival, 11%
      having nonsuffering death, and 11% having suffering death. Similar memberships of
      dying with nonsuffering conditions are found across ages among the decedents. Men
      have a higher probability of being in healthy survival and nonsuffering death as
      compared to women. Marriage, high social connections, nonsmoking, and regular
      exercise are important contributors to healthy survival and quality of death.
      DISCUSSION: It is possible to live to ages 100 and beyond without much suffering.

PMID- 22992894
TI  - Fluazuron-induced morphophysiological changes in the cuticle formation and midgut
      of Rhipicephalus sanguineus Latreille, 1806 (Acari: Ixodidae) nymphs.
AB  - The present study demonstrated the effects of the arthropod growth regulator,
      fluazuron (Acatak(r)), in the formation of the integument and digestive processes
      of Rhipicephalus sanguineus nymphs fed on rabbits treated with different doses of
      this chemical acaricide. For this, three different doses of fluazuron (20, 40, or
      80 mg/kg) were applied "pour on" to the hosts (groups II, III, and IV), as well
      as distilled water to the control group. On the first day after treatment (24 h),
      the hosts were artificially infested with R. sanguineus nymphs. After full
      engorgement (7 days), the nymphs were removed, placed on labeled Petri dishes,
      and kept in biochemical oxygen demand incubator for 7 days. The engorged nymphs
      were then taken for morphological, histochemical, and histological analyses. The
      results showed the occurrence of cytological, morphohistological, and
      histochemical alterations in the integument and midgut of nymphs from all the
      different treated groups. These alterations occurred at cuticular level in the
      subdivisions of the cuticle, related to the size of the digestive cells, amount
      of accumulated blood elements, and digestive residues, as well as the presence of
      vacuoles in the cytoplasm of the digestive cells. Thus, this study demonstrated
      that fluazuron acts on the integument and midgut cells of R. sanguineus nymphs
      fed on treated rabbits and pointed out the possibility of the use of this
      chemical-which is more specific, less toxic, and less harmful to the environment
      and nontarget organisms-in the control of R. sanguineus, at least in the nymphal
      stage of its biological cycle.

PMID- 22992895
TI  - Immunomodulatory effect of R848 on cytokine production associated with
      Schistosoma mansoni infection.
AB  - This work aimed to determine the effect of resiquimod (R848), a low molecular
      weight imidazoquinolinamine compound with properties as immune response
      modifiers, on cytokine production in patients infected with Schistosoma mansoni
      with various degrees of hepatic fibrosis. Schistosoma-infected patients were
      classified into four groups according to the degree of hepatic fibrosis as
      examined by ultrasonography group 0 (no fibrosis), group I (incipient fibrosis),
      group II (moderate fibrosis), and group III (severe fibrosis). Levels of
      interferon-gamma (IFN-gamma), interleukin 4 (IL-4), IL-10, and IL-13 were
      measured by ELISA in the supernatants of cultured peripheral blood mononuclear
      cells (PBMC) in response to schistosoma egg soluble antigen (SEA) in the presence
      and absence of R848. R848 induced a significantly higher level of IL-10 in
      supernatants of SEA-stimulated PBMC of patients in all groups of hepatic fibrosis
      except group III. Moreover, we significantly found higher levels of IFN-gamma in
      group 0 and group I and significantly lower level of IL-4 in group 0 after R848
      stimulation. However, R848 had no effect on IL-13. Taken together, these results
      suggest that R848 might be used as an immunopotentiating agent in view of novel
      therapy or vaccine for S. mansoni infection.

PMID- 22992896
TI  - Detection of toxoplasmosis in patients with end-stage renal disease by enzyme
      linked immunosorbent assay and polymerase chain reaction methods.
AB  - Toxoplasmosis caused by Toxoplasma gondii is an opportunistic infection. In
      healthy individuals, the infection is largely asymptomatic, but in
      immunocompromised people the parasite can become widely disseminated, causing
      severe toxoplasmosis. In patients undergoing haemodialysis, the phagocytic
      process shows a highly significant impairment. Therefore, this study aimed to
      investigate toxoplasmosis in patients with end-stage renal disease (ESRD)
      undergoing haemodialysis in Ahvaz hospitals, southwest of Iran. A total of 280
      patients and 100 healthy subjects participated in this study. The presence of
      serum IgM and IgG antibodies against T. gondii was detected by ELISA and the
      presence of Toxoplasma parasites in whole blood was evaluated by GRA6 PCR. Anti
      T. gondii IgG antibodies were detected in 82 (29.3 %) haemodialysis patients and
      26 (26 %) controls. In addition, anti-T. gondii IgM antibodies were detected in
      7.9 % of patients and in 4 % of controls. For both the antibodies, the
      differences were statistically significant (P < 0.05). PCR was performed with DNA
      extracted from blood samples of all patients and controls. PCR gave positive
      results with four of the 280 blood samples from patients but none for the control
      blood samples. The results revealed a high percentage of positivity for
      Toxoplasma antibodies in patients with ESRD undergoing haemodialysis and also
      confirmed the parasite in whole blood, indicating disseminated infection in these
      patients. Patients undergoing dialysis have a higher rate of active infection
      with Toxoplasma likely due to reactivation of a chronic infection. Thus,
      parasitological examinations of ESRD patients should be periodically carried out
      for monitoring and evaluating the possible dissemination of toxoplasmosis during
      haemodialysis.

PMID- 22992898
TI  - Methods for sperm concentration determination.
AB  - Proper assessment of the number of spermatozoa is essential not only as an
      initial step in every clinical infertility investigation [Bjorndahl et al (2010)
      A practical guide to basic laboratory andrology, 1st edn. Cambridge University
      Press, Cambridge] but also when attempting to establish the total sperm
      production in the testis [Amann (Hum Reprod 25:22-28, 2010); Amann (J Androl
      30:626-641, 2009); Amann and Chapman (J Androl 30:642-649, 2009)]. Reliable
      methods combined with an understanding of the specific physiology involved as
      well as the main sources of errors related to the assessment of sperm
      concentration are critical for ensuring accurate concentration determination
      [Bjorndahl et al (2010) A practical guide to basic laboratory andrology, 1st edn.
      Cambridge University Press, Cambridge; World Health Organization (2010) WHO
      laboratory manual for the examination and processing of human semen. WHO,
      Geneva]. This chapter therefore focuses on these three aspects.

PMID- 22992897
TI  - Isolation and characterization of the nematophagous fungus Arthrobotrys conoides.
AB  - The spread of organic farming and the development of resistance to anthelmintics
      by parasites, especially in small ruminants, have necessitated the search for
      alternative methods of nematode control. Biological control using nematophagous
      fungi is one option; however, few studies have been conducted with native
      strains. The present study was divided into two phases. In the first phase, we
      aimed to isolate, identify, and assess the in vitro predatory activity of
      nematophagous fungi that had been isolated on Trichostrongylidae third-instar
      larvae. In the second phase, the isolate with superior predatory activity in
      vitro was molecularly characterized, and its morphological plasticity was
      observed using scanning electron microscopy (SEM) on Haemonchus third-instar
      larvae. Of the 56 soil samples from different regions of Parana State, Brazil, 57
      fungal strains were recovered, of which four exhibited predatory activity. Two
      pure isolates were obtained: the CED and LIN strains. After demonstrating 96.35 %
      predatory activity for the CED strain, this strain was selected and characterized
      using molecular criteria by sequencing the rDNA internal transcribed spacer and
      was identified as Arthrobotrys conoides (GenBank ID: JN191309). Morphological
      patterns in this strain during the interaction between the fungus and the
      nematode were revealed by SEM, in which two extensions of the infection bulb that
      was used to pierce the nematode's cuticle were clearly visible.

PMID- 22992899
TI  - Methods of sperm vitality assessment.
AB  - Sperm vitality is a reflection of the proportion of live, membrane-intact
      spermatozoa determined by either dye exclusion or osmoregulatory capacity under
      hypo-osmotic conditions. In this chapter we address the two most common methods
      of sperm vitality assessment: eosin-nigrosin staining and the hypo-osmotic
      swelling test, both utilized in clinical Andrology laboratories.

PMID- 22992900
TI  - The hypo-osmotic swelling test for evaluation of sperm membrane integrity.
AB  - A functional membrane is requisite for the fertilizing ability of spermatozoa, as
      it plays an integral role in sperm capacitation, acrosome reaction, and binding
      of the spermatozoon to the egg surface. The hypo-osmotic swelling (HOS) test
      evaluates the functional integrity of the sperm's plasma membrane and also serves
      as a useful indicator of fertility potential of sperm. The HOS test predicts
      membrane integrity by determining the ability of the sperm membrane to maintain
      equilibrium between the sperm cell and its environment. Influx of the fluid due
      to hypo-osmotic stress causes the sperm tail to coil and balloon or "swell." A
      higher percentage of swollen sperm indicates the presence of sperm having a
      functional and intact plasma membrane. Here, we present the detailed protocol for
      performing the HOS test and explain the results for interpretation.

PMID- 22992901
TI  - Sperm morphology classification: a rational method for schemes adopted by the
      world health organization.
AB  - Sperm morphology is an important measure of testicular health, spermiation, and
      fertility potential. The World Health Organization (WHO) Semen Manuals advocate
      different sperm morphology schemes, but, like the schemes themselves, do not
      describe classification sequence or rules that can be unambiguously applied in a
      standard method. Our novel dichotomous key provides a rational decision framework
      for a sperm morphology classification algorithm. Classification order hierarchy
      is standardized and sperm characteristics are defined. Normal morphology is
      derived after eliminating abnormal and borderline normal forms. By defining and
      categorizing borderline normal forms separately from either normal or abnormal,
      the method can simultaneously produce results for Strict and traditional
      morphology schemes as adopted by different versions of the WHO Semen Manuals. The
      algorithm can be used for "recalibration" to a less stringent and potentially
      more relevant standard of normal, while reducing shift, drift, and variation in
      classification within and among analysts.

PMID- 22992902
TI  - Sperm morphology assessment using strict (tygerberg) criteria.
AB  - Although sperm morphology evaluation is one of the most important aspects of the
      semen analysis if done correctly and accurately, a trend is developing in which
      many laboratories or clinicians no longer regard sperm morphology as relevant due
      to the very low normal reference value of only 4% morphological normal
      spermatozoa given in the newest (2010) WHO-5 semen analysis manual. However, to
      maintain its relevance, sperm morphology evaluation, like the rest of the
      standard semen analysis, should be performed according to well-defined
      procedures. If performed correctly and according to high standards, morphology
      data are of high predictive value for male fertility potential and are critical
      in selecting the assisted reproductive techniques (ART) treatment. With the new
      low normal value it is becoming even more important that not only percentage
      normal and abnormal be reported but also that an in-depth report be given on the
      types of abnormalities present which will be important in selecting the type of
      clinical procedure to be adopted in ART, being, IUI, IVF, or ICSI. The methods to
      properly evaluate human sperm morphology are described in this chapter.

PMID- 22992903
TI  - Methods for direct and indirect antisperm antibody testing.
AB  - Antisperm antibodies (ASA) are one well-known cause of refractory infertility in
      both males and females. In females, a sperm immobilization test, which detects
      sperm-immobilizing antibodies indirectly in the patient's serum, requires
      complement for the reaction and thus seems to be a more specific immunological
      reaction. In males, an immunobead test or a mixed antiglobulin reaction test,
      which detects ASA directly on the sperm surface, is a screening test because of
      the nonspecific reaction.

PMID- 22992904
TI  - Manual methods for sperm motility assessment.
AB  - Progressive motility is a vital functional characteristic of ejaculated human
      spermatozoa that governs their ability to penetrate into, and migrate through,
      both cervical mucus and the oocyte vestments, and ultimately fertilize the
      oocyte. A detailed protocol, based on traditional manual/visual methods, is
      provided for performing an accurate four-category differential count including
      the reliable identification of rapid progressive (grade "a") spermatozoa-the most
      biologically, and hence clinically, important subpopulation. Thorough prior
      training and the use of a microscope fitted with a heated stage are both
      essential requirements for achieving accuracy and an acceptable uncertainty of
      measurement of no more than +/-10%.

PMID- 22992905
TI  - Computer-Aided Sperm Analysis (CASA) of sperm motility and hyperactivation.
AB  - Progressive motility is a vital functional characteristic of ejaculated human
      spermatozoa that governs their ability to penetrate into, and migrate through,
      both cervical mucus and the oocyte vestments, and ultimately fertilize the
      oocyte. A detailed protocol, based on the most common computer-aided sperm
      analysis (CASA) system with phase contrast microscope optics, is provided for
      performing reliable assessments of sperm movement pattern characteristics
      ("kinematics") in semen. The protocol can also be used with washed sperm
      suspensions where, in addition, the percentages of motile and progressively
      motile spermatozoa can also be derived. Using CASA technology it is also possible
      to identify biologically, and hence clinically, important subpopulations of
      spermatozoa (e.g., those in semen with good mucus-penetrating characteristics, or
      those showing hyperactivation when incubated under capacitating conditions) by
      applying multi-parametric definitions on a cell-by-cell basis.

PMID- 22992906
TI  - The hemizona assay for assessment of sperm function.
AB  - The hemizona assay (HZA) has been developed as a diagnostic test for the tight
      binding of human spermatozoa to the human zona pellucida to predict fertilization
      potential. In this homologous bioassay, the two matching hemizona halves are
      functionally equal surfaces allowing controlled comparison of binding from a
      fertile control versus a test sample, with reproducible measurements of sperm
      binding obtained from a single oocyte. Oocytes from different sources (surplus
      from IVF treatment or recovered from ovarian tissue) are salt-stored and used
      after microbisection. Extensive clinical data have demonstrated excellent
      predictive power of the HZA for the outcomes of intrauterine insemination and
      IVF, and therefore the assay has relevance in the clinical diagnostic setting in
      infertility.

PMID- 22992907
TI  - The sperm penetration assay for the assessment of fertilization capacity.
AB  - The sperm penetration assay, or zona-free hamster oocyte penetration assay, is
      utilized to measure the ability of sperm to undergo capacitation, fuse with the
      egg membrane, and decondense the sperm head within the cytoplasm of the oocyte,
      resulting in the formation of the male pronucleus. The test is scored by
      calculation of the percentage of ova that are penetrated (the original assay
      developed) or the average number of sperm penetrations per ovum (the sperm
      capacitation index of the optimized assay). The sperm penetration assay
      identifies those couples that will have a high likelihood of success with in
      vitro fertilization.

PMID- 22992908
TI  - Methods for the assessment of sperm capacitation and acrosome reaction excluding
      the sperm penetration assay.
AB  - Assessing the ability of human spermatozoa to acquire fertilizing potential
      (capacitation) by stimulating exocytosis of the contents of the acrosome
      (acrosome reaction) is thought to have diagnostic potential (De Jonge, Reprod Med
      Rev 3:159-178, 1994). Calcium-mobilizing agents, such as calcium ionophores
      (A23187) and progesterone, stimulate the acrosome reaction in vitro (Brucker and
      Lipford, Hum Reprod Update 1:51-62, 1995). Acrosomal status is easily detected
      using Pisum sativum Agglutinin labeled with fluorescein isothiocyanate (Cross and
      Meizel, Biol Reprod 41:635-641, 1989). Herein we describe a procedure for
      assessing capacitation and the acrosome reaction of human spermatozoa in vitro.

PMID- 22992909
TI  - Sperm DNA fragmentation analysis using the TUNEL assay.
AB  - Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end
      labeling or the TUNEL assay is an important technique in the assessment of DNA
      damage. Semen samples are routinely assessed microscopically to assess their
      fertilization ability. In addition to routine semen analysis, the use of the
      TUNEL assay can provide information on the level of DNA damage present within a
      sample. This chapter provides a practical walk-through guide aimed at directing a
      researcher or a clinical facility interested in setting up and using TUNEL and
      flow cytometry or fluorescence microscopy for sperm DNA analysis.

PMID- 22992910
TI  - Sperm DNA damage measured by comet assay.
AB  - Measurement of sperm DNA damage is a useful tool in the evaluation of male
      infertility, as the sperm nucleus lacks protection against oxidative stress and
      is vulnerable to oxidation-mediated DNA damage. The Comet assay or single-cell
      gel electrophoresis is a relatively simple and sensitive method for measuring
      strand breaks in DNA in individual sperm. During this procedure, sperm cells are
      embedded in a thin layer of agarose on a microscope slide and lysed with
      detergent under high salt conditions. This process removes protamines and
      histones allowing the nucleus to form a nucleoid-like structure containing
      supercoiled loops of DNA. Alkaline pH conditions result in unwinding of double
      stranded DNA, and subsequent electrophoresis results in the migration of broken
      strands towards the anode, forming a comet tail, when observed under fluorescence
      microscope. The amount of DNA in the head and tail is reflected by its
      fluorescent intensity. The relative fluorescence in the tail compared with its
      head serves as a measure of the level of DNA damage. In this chapter, we describe
      the alkaline version of the Comet assay, which is highly sensitive for measuring
      single- and double-strand DNA breaks.

PMID- 22992911
TI  - Sperm chromatin structure assay (SCSA(r)).
AB  - The SCSA((r)) is the pioneering assay for the detection of damaged sperm DNA and
      altered proteins in sperm nuclei via flow cytometry of acridine orange (AO)
      stained sperm. The SCSA((r)) is considered to be the most precise and repeatable
      test providing very unique, dual parameter data (red vs. green fluorescence) on a
      1,024 *  1,024 channel scale, not only on DNA fragmentation but also on abnormal
      sperm characterized by lack of normal exchange of histones to protamines. Raw
      semen/sperm aliquots or purified sperm can be flash frozen, placed in a box with
      dry ice and shipped by overnight courier to an experienced SCSA((r)) lab. The
      samples are individually thawed, prepared, and analyzed in ~10 min. Of
      significance, data on 5,000 individual sperm are recorded on a 1,024  *  1,024
      dot plot of green (native DNA) and red (broken DNA) fluorescence. Repeat
      measurements have virtually identical dot plot patterns demonstrating that the
      low pH treatment that opens up the DNA strands at the sites of breaks and
      staining by acridine orange (AO) are highly precise and repeatable (CVs of 1-3%)
      and the same between fresh and frozen samples. SCSAsoft((r)) software transforms
      the X-Y data to total DNA stainability versus red/red  +  green fluoresence (DFI)
      providing a more accurate determination of % DFI as well as the more sensitive
      value of standard deviation of DFI (SD DFI) as demonstrated by animal fertility
      and dose-response toxicology studies. The current established clinical threshold
      is 25% DFI for placing a man into a statistical probability of the following: (a)
      longer time to natural pregnancy, (b) low odds of IUI pregnancy, (c) more
      miscarriages, or (d) no pregnancy. Changes in lifestyle as well as medical
      intervention can lower the %DFI to increase the probability of natural pregnancy.
      Couples of men with >25% DFI are counseled to try ICSI and when in the >50% range
      may consider TESE/ICSI. The SCSA((r)) simultaneously determines the % of sperm
      with high DNA stainability (%HDS) related to retained nuclear histones consistent
      with immature sperm; high HDS values are predictive of pregnancy failure.The
      SCSA((r)) is considered to be the most technician friendly, time- and cost
      efficient, precise and repeatable DNA fragmentation assay, with the most data and
      the only fragmentation assay with an accepted clinical threshold for placing a
      man at risk for infertility. SCSA((r)) data are more predictive of male factor
      infertility than classical semen analyses.

PMID- 22992912
TI  - Sperm aneuploidy testing using fluorescence in situ hybridization.
AB  - Sperm aneuploidy screening has been used as a tool in diagnosis and determining
      treatment options for male factor infertility since the development of human
      sperm karyotyping by injection into hamster and mouse oocytes in the 1970s. From
      these studies and subsequent work with interphase chromosome analysis, at risk
      populations of men with teratozoospermia, oligozoospermia, and men with
      translocations, have since been identified. The current technique is an
      application of fluorescent in situ hybridization (FISH) on interphase sperm
      nuclei with careful enumeration of the labeled chromosomes to determine sperm
      ploidy. Typically, five to seven chromosomes are evaluated in individual
      ejaculates to determine the percent of aneuploid sperm present. This protocol
      will detail the procedures for: preparation of specimens, exposure of the sperm
      nuclei to the FISH probes, hybridization, destaining, and scoring criteria.

PMID- 22992913
TI  - Flow cytometric methods for sperm assessment.
AB  - Flow cytometry allows the assessment of multiple sperm parameters following a
      diverse number of protocols. Here, we describe three methods for evaluating
      critical aspects of sperm quality: the double stain SYBR-14 and propidium iodide
      (PI) for assessing sperm viability; the double stain PNA-FITC (peanut agglutinin
      fluorescein isothiocyanate) and PI for assessing acrosomal integrity combined
      with sperm viability; and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl
      benzimidazolylcarbocyanine iodide) for assessing mitochondrial membrane
      potential. These three stains are widely used and can be analyzed with basic flow
      cytometers.

PMID- 22992914
TI  - Human Y chromosome microdeletion analysis by PCR multiplex protocols identifying
      only clinically relevant AZF microdeletions.
AB  - PCR multiplex assays are the method of choice for quickly revealing genomic
      microdeletions in the large repetitive genomic sequence blocks on the long arm of
      the human Y chromosome. They harbor the Azoospermia Factor (AZF) genes, which
      cause male infertility when functionally disrupted. These protein encoding Y
      genes are expressed exclusively or predominantly during male germ cell
      development, i.e., at different phases of human spermatogenesis. They are located
      in three distinct genomic sequence regions designated AZFa, AZFb, and AZFc,
      respectively. Complete deletion of an AZF region, also called "classical" AZF
      microdeletion, is always associated with male infertility and a distinct
      testicular pathology. Partial AZF deletions including single AZF Y genes can
      cause the same testicular pathology as the corresponding complete deletion (e.g.,
      DDX3Y gene deletions in AZFa), or might not be associated with male infertility
      at all (e.g., some BPY2, CDY1, DAZ gene deletions in AZFc). We therefore propose
      that a PCR multiplex assay aimed to reduce only those AZF microdeletions causing
      a specific testicular pathology-thus relevant for clinical applications. It only
      includes Sequence Tagged Site (STS) deletion markers inside the exon structures
      of the Y genes known to be expressed in male germ cells and located in the three
      AZF regions. They were integrated in a robust standard protocol for four PCR
      multiplex mixtures which also include the basic principles of quality control
      according to the strict guidelines of the European Molecular Genetics Quality
      Network (EMQN: http://www.emqn.org). In case all Y genes of one AZF region are
      deleted the molecular extension of this AZF microdeletion is diagnosed to be yes
      or no comparable to that of the "classical" AZF microdeletion by an additional
      PCR multiplex assay analyzing the putative AZF breakpoint borderlines.

PMID- 22992915
TI  - Sperm cryopreservation methods.
AB  - There are multiple clinical situations where cryopreservation of sperm is
      required including sperm banking prior to chemotherapy or radiation treatment for
      cancer, donor sperm for couples without a male partner, and various etiologies of
      male factor infertility. Bunge and Sherman presented the first pregnancy
      resulting from the thawing of cryopreserved sperm in 1953 (Bunge RJ, Nature
      172:767-768, 1953). Since that time, cryopreservation techniques have continued
      to improve. Here, we describe protocols for the cryopreservation and thawing of
      semen and testicular tissues using a simple liquid nitrogen vapor technique.

PMID- 22992916
TI  - Density gradient separation of sperm for artificial insemination.
AB  - Human spermatozoa for clinical procedures such as IUI or IVF, or for diagnostic
      or research studies of sperm fertilizing ability, must be separated from the
      seminal plasma environment not only as soon as possible after ejaculation but
      also as efficiently as possible, minimizing seminal plasma and bacterial
      carryover. Furthermore, in addition to technical simplicity and robustness, a
      sperm preparation method needs to select not just the more motile and
      morphologically normal spermatozoa but also those spermatozoa with reduced DNA
      damage. Currently the most effective and efficient technique for this is density
      gradient centrifugation, which has been extensively validated through research
      and clinical application. An optimized protocol based on silane-coated colloidal
      silica products is provided.

PMID- 22992917
TI  - Recovery, isolation, identification, and preparation of spermatozoa from human
      testis.
AB  - In some cases, human spermatozoa to be used for in vitro fertilization are
      processed from testicular or epididymal biopsies collected in the clinic or
      operating room. An appropriately equipped Andrology or Embryology Laboratory is
      required. Sterility must be maintained at all stages from collection and
      transport to identification and processing to insemination or cryopreservation.
      The technologist must be able to properly process and identify spermatozoa from
      aspirates, seminiferous tubules or pieces of testicular tissue. Recovery of
      undamaged spermatozoa from tubules or tissue requires mincing, squeezing, or
      vortexing the tissue, usually without the need of enzymatic digestion. A motility
      stimulant such as Pentoxifylline is commonly used to calculate the number of
      functionally competent spermatozoa. After recovery, spermatozoa may be used
      immediately for IVF-ICSI, incubated overnight prior to IVF-ICSI, or cryopreserved
      for future use. Methods for identifying, purifying, and determining the number
      and motility of spermatozoa during these processes are presented.

PMID- 22992918
TI  - Enhancement of sperm motility using pentoxifylline and platelet-activating
      factor.
AB  - Enhancement of sperm motility can effectively improve assisted reproductive
      technique outcomes. Here we describe two (pentoxifylline and platelet-activating
      factor) popular sperm motility enhancers and their respective methods.

PMID- 22992919
TI  - Intracytoplasmic morphology-selected sperm injection.
AB  - Approximately 40% of sterility in couples can be attributed to male subfertility
      and intracytoplasmic sperm injection (ICSI) has become a powerful tool in
      assisted reproduction to overcome male infertility. Intracytoplasmic
      morphologically selected sperm injection (IMSI) is an advanced and sophisticated
      method of ICSI, where prior to sperm injection the morphology of the sperm is
      evaluated under high magnification. In addition, the IMSI procedure involves a
      few minor modifications in sperm preparation which are not carried out during the
      conventional ICSI procedure, such as the use of MSOME criteria, the requirement
      for a glass-bottomed dish for selection, prolonged sperm manipulation following
      separation from the seminal fluid, and sperm storage prior to microinjection.
      These variations are discussed in this chapter.

PMID- 22992920
TI  - Sperm selection for ICSI using annexin V.
AB  - Annexin-V magnetic-activated cell sorting (MACS) is a new tool to optimize sperm
      selection in assisted reproduction. The technique is based on the binding of
      superparamagnetic Annexin-microbeads to externalized phosphatidylserine at the
      outer leaflet of the plasma membrane of sperm with activated apoptosis signaling
      or membrane damage. The combination of Annexin-V MACS and density gradient
      centrifugation was demonstrated to enhance clinical pregnancy rates in ICSI
      cycles. This chapter focuses on the practical details of Annexin-V MACS.

PMID- 22992921
TI  - Sperm selection for ICSI using the hyaluronic acid binding assay.
AB  - Sperm selection is an important part of the ICSI procedure. Routinely, sperm
      selection for ICSI is based solely on sperm morphology and motility. These latter
      parameters may not be sufficient to select sperm with intact chromatin.
      Therefore, sperm selected based on sperm functional characteristics may result in
      the most appropriate sperm for the ICSI procedure. The methodology explained
      below describes the selection of sperm based on the ability of sperm to bind
      solid-state hyaluronic acid as its receptor, present on mature sperm with intact
      chromatin.

PMID- 22992922
TI  - Sperm selection based on electrostatic charge.
AB  - Charge is a fundamental property of all forms of matter that exhibit attraction
      or repulsion in the presence of another charged particle. This electrokinetic
      property occurs when the particles exhibiting a net negative or positive charge
      are subjected to an external electric field that exerts an electrostatic force
      between them. Sperm surface membranes exhibit varying levels of electrostatic
      potential that are proportional to the levels of sialic acid residue acquired on
      the cell surface during maturation. Electrostatic charge-based sperm separation
      is a recently developed technique that uses an electric field to isolate mature
      sperm with reduced levels of DNA fragmentation. Two methods for the separation of
      sperm based on electrostatic charge, the Zeta method and a commercially available
      electrophoretic method using the SpermSep Cell Sorter 10, are discussed in this
      chapter including a detailed protocol for sperm separation based on the Zeta
      method.

PMID- 22992923
TI  - Sex-sorting sperm using flow cytometry/cell sorting.
AB  - The sex of mammalian offspring can be predetermined by flow sorting relatively
      pure living populations of X- and Y-chromosome-bearing sperm. This method is
      based on precise staining of the DNA of sperm with the nucleic acid-specific
      fluorophore, Hoechst 33342, to differentiate between the subpopulations of X- and
      Y-sperm. The fluorescently stained sperm are then sex-sorted using a specialized
      high speed sorter, MoFlo((r)) SX XDP, and collected into biologically supportive
      media prior to reconcentration and cryopreservation in numbers adequate for use
      with artificial insemination for some species or for in vitro fertilization.
      Sperm sorting can provide subpopulations of X- or Y-bearing bovine sperm at rates
      in the 8,000 sperm/s range while maintaining; a purity of 90% such that it has
      been applied to cattle on a commercial basis. The sex of offspring has been
      predetermined in a wide variety of mammalian species including cattle, swine,
      horses, sheep, goats, dogs, cats, deer, elk, dolphins, water buffalo as well as
      in humans using flow cytometric sorting of X- and Y-sperm.

PMID- 22992924
TI  - Assessment of spermatogenesis through staging of seminiferous tubules.
AB  - Male germ cells in all mammals are arranged within the seminiferous epithelium of
      the testicular tubules in a set of well-defined cell associations called stages.
      The cellular associations found in these stages and characteristics of the cells
      used to identify the stages have been well described. Here we present a binary
      decision key roadmap for identifying stages and present several examples of how
      staging tubules can be used to better assess the developmental profile of gene
      expression during spermatogenesis and defects in spermatogenesis arising in
      pathological conditions resulting from genetic mutations in mice. In particular,
      when one or more cells of a cellular association cannot be clearly identified or
      are missing, the cell types that should be present can be precisely identified by
      knowledge of the approximate or exact stage of the tubule cross section.

PMID- 22992925
TI  - Immunohistochemical approaches for the study of spermatogenesis.
AB  - Immunohistochemistry is an important technique that uses specific antibodies to
      determine the cellular localization of proteins/antigens in highly complex organs
      and tissues. While most immunohistochemistry experiments target protein epitopes,
      nonprotein antigens including BrdU may also be detected. Briefly, tissues are
      fixed, processed, sectioned, and then probed by a primary antibody while
      preserving the integrity of the tissue and cellular morphology. There are various
      methods available for visualization of the bound primary antibody that involve a
      reporter molecule which can be detected using light or fluorescent microscopy.
      Here we describe a basic immunohistochemistry protocol for identifying protein
      localization in testis sections using protein-specific antibodies.

PMID- 22992926
TI  - Ultrastructural analysis of testicular tissue and sperm by transmission and
      scanning electron microscopy.
AB  - Transmission electron microscopy (TEM) studies have provided the basis for an in
      depth understanding of the cell biology and normal functioning of the testis and
      male gametes and have opened the way to characterize the functional role played
      by specific organelles in spermatogenesis and sperm function. The development of
      the scanning electron microscope (SEM) extended these boundaries to the
      recognition of cell and organ surface features and the architectural array of
      cells and tissues. The merging of immunocytochemical and histochemical approaches
      with electron microscopy has completed a series of technical improvements that
      integrate structural and functional features to provide a broad understanding of
      cell biology in health and disease. With these advances the detailed study of the
      intricate structural and molecular organization as well as the chemical
      composition of cellular organelles is now possible. Immunocytochemistry is used
      to identify proteins or other components and localize them in specific cells or
      organelles with high specificity and sensitivity, and histochemistry can be used
      to understand their function (i.e., enzyme activity). When these techniques are
      used in conjunction with electron microscopy their resolving power is further
      increased to subcellular levels. In the present chapter we will describe in
      detail various ultrastructural techniques that are now available for basic or
      translational research in reproductive biology and reproductive medicine. These
      include TEM, ultrastructural immunocytochemistry, ultrastructural histochemistry,
      and SEM.

PMID- 22992927
TI  - Assessment of oxidative stress in sperm and semen.
AB  - The chemiluminescence method is the most commonly employed technique as a direct
      measurement of reactive oxygen species (ROS) generation by spermatozoa. This
      assay is capable of quantifying both intracellular and extracellular ROS.
      Moreover, the use of various probes allows for differentiation between superoxide
      and hydrogen peroxide production by spermatozoa. When the total antioxidant
      reserves are overwhelmed by excessive production of ROS, it results in oxidative
      stress. Therefore correct measurement of both ROS and total antioxidant capacity
      (TAC) is essential in the assessment of oxidative stress in sperm and semen. This
      chapter describes the methodological approach for measuring seminal oxidative
      stress through the use of chemiluminescence assay for accurate measurement of ROS
      and the colorimetric assay for measurement of TAC.

PMID- 22992928
TI  - Improved chemiluminescence assay for measuring antioxidant capacity of seminal
      plasma.
AB  - An improved enhanced chemiluminescence antioxidant assay utilizes horseradish
      peroxidase conjugate and luminol to produce a cell-free oxygen radical generating
      system. We introduce the use of a peroxidase enzyme stabilizer to prolong the
      production of oxygen radicals at a steady rate. Addition of antioxidants
      temporarily interrupts oxygen radical generation, resulting in an inhibition
      curve. A linear relationship exists between the area of the inhibition curve and
      the molar quantity of added antioxidant used to quantify total nonenzymatic
      antioxidant capacity (TAC) in biological fluids including seminal plasma. We
      streamline the existing enhanced chemiluminescence technique by using a
      microtiter plate luminometer. A plate luminometer is as accurate as a tube
      luminometer in measuring TAC, using identical reaction volumes. As little as 1-50
      MUL of sample may be analyzed. A plate luminometer can detect molar Trolox
      equivalents as low as 12.5 MUM, compared to 25 MUM in tube luminometer, using
      identical volumes. The plate luminometer assay is made even more rapid with use
      of an injector.

PMID- 22992929
TI  - Methods of sperm DNA extraction for genetic and epigenetic studies.
AB  - High quality DNA extractions developed for mammalian somatic cells are
      ineffective for sperm, due mainly to the high degree of nuclear compaction in
      sperm. The highly specialized nuclear proteins in sperm create a chromatin
      structure that is at least six times denser than histone bound DNA. Unlike
      somatic cells, sperm DNA is highly compacted by the replacement of histones with
      sperm-specific low molecular weight proteins called protamines. Both the
      protamines and the disulfide bridges formed within and between protamines inhibit
      the extraction of sperm DNA by standard techniques used for somatic cells. Here
      we describe the guanidine thiocyanate method reported by Hossain with additional
      modifications resulting in high molecular weight DNA of high quality with an
      A260/280 ratio ranging between 1.8 and 2.0 and an A260/230 ratio of 2.0 and
      greater. The DNA is efficiently digested with restriction enzymes and amplified
      by PCR.

PMID- 22992930
TI  - Isolating mRNA and small noncoding RNAs from human sperm.
AB  - The isolation of spermatozoal RNA is a challenging procedure due to the intrinsic
      heterogeneous population of cells present in the ejaculate and the small quantity
      of RNA present in sperm. The transcriptome of these gametes includes a wide
      variety of messenger RNAs (mRNAs), small noncoding RNAs (sncRNAs), and highly
      fragmented ribosomal RNAs (rRNAs).The protocol described in this chapter to
      isolate both the mRNA and sncRNA fractions represents years of development
      towards automation. It combines a guanidinium thiocyanate-phenol-chloroform-based
      methodology to reduce the content of DNA and a column-based system. Both manual
      and semi-automated options are described, with preference given to automation for
      consistent results. A novel quality control procedure has been developed to
      assess the integrity and purity of the entire population of isolated mRNAs due to
      the absence of intact rRNAs.

PMID- 22992931
TI  - A review of genome-wide approaches to study the genetic basis for spermatogenic
      defects.
AB  - Rapidly advancing tools for genetic analysis on a genome-wide scale have been
      instrumental in identifying the genetic bases for many complex diseases. About
      half of male infertility cases are of unknown etiology in spite of tremendous
      efforts to characterize the genetic basis for the disorder. Advancing our
      understanding of the genetic basis for male infertility will require the
      application of established and emerging genomic tools. This chapter introduces
      many of the tools available for genetic studies on a genome-wide scale along with
      principles of study design and data analysis.

PMID- 22992932
TI  - Methods for the analysis of the sperm proteome.
AB  - Proteomics is the study of the proteins of cells or tissues. Sperm proteomics
      aims at the identification of the proteins that compose the sperm cell and the
      study of their function. The recent developments in mass spectrometry (MS) have
      markedly increased the throughput for the identification and study of the sperm
      proteins. Catalogues of spermatozoal proteins in human and in model species are
      becoming available laying the groundwork for subsequent research, diagnostic
      applications, and the development of patient-specific treatments. A wide range of
      MS techniques is also rapidly becoming available for researchers. This chapter
      describes a methodological option to study the sperm cell using MS and provides a
      detailed protocol to identify the proteins extracted from a Percoll-purified
      human sperm population and separated by two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) using LC-MS/MS.

PMID- 22992933
TI  - Methodology of aniline blue staining of chromatin and the assessment of the
      associated nuclear and cytoplasmic attributes in human sperm.
AB  - In this chapter, the laboratory methods for detection of sperm biomarkers that
      are aimed at identifying arrested sperm development are summarized. These probes
      include sperm staining with aniline blue for persistent histones, representing a
      break in the histone-transition protein-protamine sequence, immunocytochemistry
      with cytoplasmic sperm proteins, highlighting cytoplasmic retention during
      spermiogenesis, DNA nick translation testing for DNA chain fragmentation due to
      various reasons, for instance low HspA2 chaperone protein levels, and
      consequential diminished DNA repair. Finally, we briefly provide references on
      our work on sperm hyaluronan binding, abnormal Tybergerg sperm morphology, and
      the increased levels of chromosomal aneuploidies in sperm with developmental
      arrest. A very interesting aspect of the biomarker field is the discovery (Sati
      et al, Reprod Biomed Online 16:570-579, 2008) that the various nuclear and
      cytoplasmic defects detected by the biomarkers are related, and may
      simultaneously occur within the same spermatozoa as evidenced by a combination of
      biomarkers, such as aniline blue staining (persistent histones) coupled with
      cytoplasmic retention, DNA fragmentation, Caspase-3, Tygerberg abnormal
      morphology, and increased levels of chromosomal aneuploidies. We show examples of
      this >80% overlap in staining patterns within the same spermatozoa.

PMID- 22992934
TI  - Isolation of sperm nuclei and nuclear matrices from the mouse, and other rodents.
AB  - The isolation of mammalian sperm heads from their tails is complicated by the
      relatively high density of the tails, but facilitated by the fact that protamine
      condensation of the sperm chromatin and the insolubility of the perinuclear theca
      make the sperm nucleus stable in sodium dodecyl sulfate. Two methods are
      described for the isolation of rodent sperm nuclei using sucrose step gradients
      in which the sperm nuclei are only centrifuged one time, minimizing potential
      damage by mechanical stress.

PMID- 22992935
TI  - Protamine extraction and analysis of human sperm protamine 1/protamine 2 ratio
      using Acid gel electrophoresis.
AB  - Protamines, sperm-specific nuclear proteins, are essential for sperm chromatin
      condensation and DNA stabilization. They are small, highly basic, and rich in
      disulfide bonds. Under reducing conditions, protamines, along with other basic
      proteins, are soluble in acid solutions. Because of their small and similar
      molecular weights, SDS-PAGE cannot resolve protamine 1 and protamine 2 well. Urea
      acid gel electrophoresis separates proteins based on the level of the positive
      charge and is thus a suitable method for resolving protamines 1 and 2. Here, we
      describe the commonly used protamine extraction method and the Urea-acid gel
      electrophoresis for assessment of protamine 1/protamine 2 ratio.

PMID- 22992936
TI  - Analysis of gene-specific and genome-wide sperm DNA methylation.
AB  - Epigenetic modifications on the DNA sequence (DNA methylation) or on chromatin
      associated proteins (i.e., histones) comprise the "cellular epigenome"; together
      these modifications play an important role in the regulation of gene expression.
      Unlike the genome, the epigenome is highly variable between cells and is dynamic
      and plastic in response to cellular stress and environmental cues. The role of
      the epigenome, specifically, the methylome has been increasingly highlighted and
      has been implicated in many cellular and developmental processes such as
      embryonic reprogramming, cellular differentiation, imprinting, X chromosome
      inactivation, genomic stability, and complex diseases such as cancer. Over the
      past decade several methods have been developed and applied to characterize DNA
      methylation at gene-specific loci (using either traditional bisulfite sequencing
      or pyrosequencing) or its genome-wide distribution (microarray analysis following
      methylated DNA immunoprecipitation (MeDIP-chip), analysis by sequencing (MeDIP
      seq), reduced representation bisulfite sequencing (RRBS), or shotgun bisulfite
      sequencing). This chapter reviews traditional bisulfite sequencing and shotgun
      bisulfite sequencing approaches, with a greater emphasis on shotgun bisulfite
      sequencing methods and data analysis.

PMID- 22992937
TI  - Evaluating the localization and DNA binding complexity of histones in mature
      sperm.
AB  - The paternal genome in many animal taxa is efficiently packaged into the sperm
      nucleus by switching from a histone (nucleosome)-based chromatin configuration to
      one using predominantly protamines. Nonetheless, various studies have shown that
      some nucleosomes, often containing modified histones are retained in mature sperm
      and bind DNA with distinct sequence compositions. Considering the significance of
      histone modifications in epigenetic phenomena and the fact that sperm histones
      and their bound DNA must be carried into the oocyte, this chapter describes
      methods aimed at examining and analysing the histone composition of sperm
      chromatin. The focus is on both microscopic visualisation and evaluation of
      sequence composition of histones and histone-bound DNA in human and mouse
      spermatozoa. However, similar methods may be applicable to the sperm of other
      mammalian and even non-mammalian classes.

PMID- 22992938
TI  - In vitro spermatogenesis using an organ culture technique.
AB  - Research on in vitro spermatogenesis has a long history and remained to be an
      unaccomplished task until very recently. In 2010, we succeeded in producing
      murine sperm from primitive spermatogonia using an organ culture method. The
      fertility of the sperm or haploid spermatids was demonstrated by
      microinsemination. This organ culture technique uses the classical air-liquid
      interphase method and is based on conditions extensively examined by Steinbergers
      in 1960s. Among adaptations in the new culture system, application of serum-free
      media was the most important. The system is very simple and easy to follow.

PMID- 22992939
TI  - Testicular tissue grafting and male germ cell transplantation.
AB  - Testicular tissue grafting and male germ cell transplantation are techniques that
      offer unprecedented opportunities to study testicular function and development.
      While testicular tissue grafting allows recapitulation of testis development and
      spermatogenesis from immature males of different mammalian species in recipient
      mice, germ cell transplantation results in donor-derived spermatogenesis in
      recipient testes.Testicular tissue grafting results in spermatogenesis from a
      wide variety of large animal donor species and is therefore an attractive way to
      study testis development and spermatogenesis and preserve fertility of immature
      males. Germ cell transplantation represents a functional reconstitution assay for
      identification of spermatogonial stem cells (SSCs) in a given donor cell
      population and serves as a valuable tool to study stem cell biology and
      spermatogenesis. In this chapter we provide detailed methodology to successfully
      perform both techniques.

PMID- 22992940
TI  - Transgenic modification of spermatogonial stem cells using lentiviral vectors.
AB  - The continuous production of spermatazoa throughout the reproductive lifetime of
      a male depends on the maintenance of a pool of progenitor cells called
      spermatogonial stem cells (SSCs). SSCs represent a very small fraction of the
      cellular population in the testes and lack definitive molecular markers for their
      identification. The discovery of conditions that allow one to propagate mouse
      SSCs in vitro essentially indefinitely has truly facilitated studies of the
      molecular mechanisms regulating SSC function. While multiple conditions for
      culturing SSCs have now been described, here we detail a method for culturing
      SSCs that uses a simpler medium than the original formulation. As with numerous
      other primary and stem cell cultures, it is difficult to introduce DNA into
      cultured SSCs using standard transfection approaches. However, VSV-G pseudotyped
      lentivirus efficiently infects cultured SSCs with minimal toxicity. Here we
      present protocols for producing lentivirus and stably modifying the genome of
      cultured SSCs using lentiviral vectors.

PMID- 22992941
TI  - Methods for sperm-mediated gene transfer.
AB  - The transgenic technologies represent potent biotechnological tools that allow
      the generation of genetically modified animals useful for basic research and for
      biomedical, veterinary, and agricultural applications. Among transgenic
      techniques, we describe here the sperm-mediated gene transfer methods that is
      gene transfer based on the spontaneous ability of sperm cells to bind and
      internalize exogenous DNA and to carry it to oocyte during fertilization,
      producing genetically modified animals with high efficiency.

PMID- 22992942
TI  - Phenotypic assessment of male fertility status in transgenic animal models.
AB  - This chapter describes the approach to define the cause of male infertility in a
      genetically modified male mouse. It provides a guide to the establishment of the
      infertility status and whether it is due to the failure of mating or due to
      abnormalities of the sperm output, motility, and morphology. Further assessments
      define the nature of the spermatogenic defects and their severity and are
      designed to determine the pathogenic mechanisms involved.

PMID- 22992943
TI  - Likeability and abuse liability of commonly prescribed opioids.
AB  - INTRODUCTION: Nonmedical use of prescription opioid analgesics is associated with
      epidemic levels of morbidity and mortality. There are several factors that affect
      the abuse liability of the various opioids, including likability or the
      pleasurable subjective effects. Due to rising public health concerns over
      escalating prescription opioid abuse, we sought to examine the literature about
      abuse liability with a specific focus on likability studies. METHODS: A search of
      EMBASE and MEDLINE databases identified articles that described the comparative
      likeability and/or abuse potential of hydrocodone and oxycodone relative to each
      other and/or of either one to morphine. After an assessment of study quality
      using the Oxford/Jadad scale, relevant details such as demographics, study
      design, and outcome measures were compiled into an evidence table. RESULTS: We
      identified nine studies that met inclusion criteria. All were double-blinded,
      randomized, placebo-controlled crossover studies and scored 5 out of 5 Jadad
      scale. There was no consistent clinically significant difference between abuse
      liability of morphine and hydrocodone. Oxycodone demonstrated high abuse
      liability on the basis of its high likability scores and a relative lack of
      negative subjective effects. CONCLUSION: Oral oxycodone has an elevated abuse
      liability profile compared to oral morphine and hydrocodone.

PMID- 22992944
TI  - Downregulation of AKT reverses platinum resistance of human ovarian cancers in
      vitro.
AB  - Platinum resistance is the most crucial problem for treatment of ovarian cancer.
      Increasing evidence points towards AKT overexpression as a mechanistic reason for
      this clinical condition. The present study evaluates the effect of overexpression
      and downregulation of AKT on the sensitivity to cisplatin in a platinum-resistant
      human ovarian cancer cell line and the corresponding platinum-sensitive parental
      cell line. A2780 and A2780cis ovarian cancer cell lines were stably transfected
      with an AKT-sense and AKT-antisense plasmid. Successful transfection was
      evaluated by western blot analysis. Cytotoxic effects of cisplatin were evaluated
      by metabolic (MTT) and clonogenicity assays as well as by FACS analysis. AKT
      overexpression (confirmed by western blotting) converted platinum-sensitive A2780
      into platinum-resistant cells as shown by MTT assay. Importantly, platinum
      resistance of A2780cis cells could be reversed by downregulation of AKT, as
      demonstrated by MTT and clonogenicity assays and FACS analysis. Our data provide
      strong evidence that cisplatin resistance in ovarian cancer is mediated by AKT
      overexpression and can be overcome by AKT downregulation, thus, providing a
      rationale for clinical phase II/III studies combining AKT inhibitors with
      cisplatin.

PMID- 22992945
TI  - Sphingosine-1-phosphate inhibits interleukin-1beta-induced inflammation in human
      articular chondrocytes.
AB  - Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits
      signals through a family of G-protein-coupled receptors (GPCRs) to control
      diverse biological processes including inflammation and wound-healing. In this
      study, a novel biological activity of S1P in articular chondrocytes was
      identified. Human primary chondrocytes were cultured in a monolayer. Reverse
      transcription-polymerase chain reaction (RT-PCR) and western blotting were
      performed to detect genes and proteins involved in inflammation and cartilage
      degradation when human primary chondrocytes were stimulated by interleukin (IL)
      1beta. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was evaluated by
      gelatin zymography. Glycosaminoglycan (GAG) degradation was evaluated using the
      dimethylene blue method. Prostaglandin E2 (PGE2) was measured by enzyme-linked
      immunosorbent assay (ELISA). By using the S1P1 receptor agonist and antagonist,
      we discovered the key role played by S1P1 in the S1P-dependent inhibition of IL
      1beta-induced inflammation in human chondrocytes. S1P dose-dependently inhibited
      IL-1beta-induced NF-kappaB p65, cyclooxygenase (COX)-2, MMP-1, MMP-3, MMP-13 and
      MMP-14 mRNA expression in human chondrocytes and IL-1beta-induced PGE2 synthesis
      and GAG degradation in human cartilage explants. W146, a known S1P1 receptor
      antagonist, inhibited the active form of NF-kappaB p65 and COX-2 expression
      induced by IL-1beta. The anti-inflammatory action of the S1P1 receptor agonist
      SEW2871 was similar to that of S1P. This study demonstrates that S1P has anti
      inflammatory effects on chondrocytes via the S1P1 receptor. Our data suggest that
      targeting S1P and S1P1 may be a potential therapy for arthritis.

PMID- 22992946
TI  - Electrical impedance tomography: the holy grail of ventilation and perfusion
      monitoring?
AB  - This review summarizes the state-of-the-art in electrical impedance tomography
      (EIT) for ventilation and perfusion imaging. EIT is a relatively new technology
      used to image regional impedance distributions in a cross-sectional area of the
      body. After the introduction, a brief overview of the recent history is provided
      followed by a review of the literature on regional ventilation monitoring using
      EIT. Several recently presented indices that are useful to extract information
      from EIT image streams are described. Selected experimental and clinical findings
      are discussed with respect to future routine applications in intensive care.
      Finally, past and ongoing research activities aimed at obtaining cardiac output
      and regional perfusion information from EIT image streams are summarized.

PMID- 22992947
TI  - Gastrointestinal nematode burden in working equids from humid tropical areas of
      central Veracruz, Mexico, and its relationship with body condition and
      haematological values.
AB  - The east coast of Veracruz, Mexico, has an important equine population used for
      working in rural production systems. The objectives of this study were (1) to
      calculate the prevalence of tropical working equids (donkeys, mules and horses)
      infected with gastrointestinal nematodes (GINs) and the GINs involved, and (2) to
      measure the body condition score (BCS) and haematological values for each working
      equid and its relationship with faecal worm egg count (EPG). One hundred and
      forty working equids were randomly selected from five different villages along
      the central coast of the state of Veracruz and faecal and blood samples were
      obtained from each animal. Gastrointestinal parasite burdens were determined
      using the McMaster technique. Packed cell volume, total plasma proteins, red
      blood cell count and white blood cell count were measured from each blood sample.
      Prevalence of infected equids was higher than 90 %. Mules had the highest median
      faecal worm egg counts (875 EPG), followed by horses and donkeys with 400 EPG.
      There was no correlation between EPG and BCS or haematological values (p > 0.05).
      Results suggest that despite the high prevalence and parasite burdens, equids
      involved in this trial are not being seriously affected. This study provides
      information which might help in designing future strategies to control nematode
      infections in working equids in the Mexican tropics; more emphasis should be
      placed on other inputs (nutrition perhaps), with individual anthelminthic
      treatment to those animals with the highest EPG or when signs present themselves.

PMID- 22992948
TI  - Upregulation of Mad2 facilitates in vivo and in vitro osteosarcoma progression.
AB  - It has been reported that overexpression of Mad2 in transgenic mice leads to a
      wide variety of tumors, and Mad2 overexpression causes lung tumor relapse after
      oncogene withdrawal. In a previous study we demonstrated that Mad2 is abnormally
      upregulated in human osteosarcoma, however, the underlying mechanisms remain
      unknown. In this study, we found that transient Mad2 overexpression is sufficient
      to cause early dyscrasia and decreased survival in a xenotransplantation
      osteosarcoma mouse model, and Mad2 overexpression is associated with increased
      invasiveness and pulmonary metastasis. We also found that upregulation of Mad2
      was accompanied by enhanced capability to self-renew. Our data validate the
      correlation between upregulation of Mad2 and osteosarcoma advancement, and that
      the underlying mechanisms involve the increase of invasiveness and cancer stem
      cell properties.

PMID- 22992949
TI  - Diagnosis of contact injuries in a mediaeval skeleton analysed by uCT and
      histology.
AB  - During an archaeological excavation in Altenberg/Linz (Upper Austria), the well
      preserved skeletal remains of a mature male dated the 13th century AD were
      recovered. Several elements of the skeleton yielded alterations caused by trauma:
      beside a malunion of the left ulna which was accompanied by shortening of the
      diaphysis, a luxation and deformation of the left radial head was observed
      (Monteggia-type lesion, Bado-type I). Moreover, at the anterior aspect of the
      corresponding humerus, a chalice-shaped, newly built bone structure that framed
      the displaced capitulum radii was visible. This structure formed a sort of
      "alternative joint" that functionally even allowed some movements, although
      considerably restricted in regard to flexion/extension and even more in
      pronation/supination.To verify the assumption of a "single event", we not only
      investigated the concerned skeletal portions by gross-anatomical examination, but
      also by non-invasive conventional radiological, micro-computed tomographical, and
      histological techniques. Particular morphological features, injuries at the
      calvarium, and fractures of other postcranial elements imply the scenario of a
      close combat; although survived, the traumata obviously resulted in partial
      invalidity.

PMID- 22992950
TI  - Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and
      postnatal physiology.
AB  - The Iroquois homeobox (Irx) homeodomain transcription factors are important for
      several aspects of embryonic development. In the developing heart, individual Irx
      genes are important for certain postnatal cardiac functions, including cardiac
      repolarization (Irx5) and rapid ventricular conduction (Irx3). Irx genes are
      expressed in dynamic and partially overlapping patterns in the developing heart.
      Here we show in mice that Irx3 and Irx5 have redundant function in the
      endocardium to regulate atrioventricular canal morphogenesis and outflow tract
      formation. Our data suggest that direct transcriptional repression of Bmp10 by
      Irx3 and Irx5 in the endocardium is required for ventricular septation. A
      postnatal deletion of Irx3 and Irx5 in the myocardium leads to prolongation of
      atrioventricular conduction, due in part to activation of expression of the Na(+)
      channel protein Nav1.5. Surprisingly, combined postnatal loss of Irx3 and Irx5
      results in a restoration of the repolarization gradient that is altered in Irx5
      mutant hearts, suggesting that postnatal Irx3 activity can be repressed by Irx5.
      Our results have uncovered complex genetic interactions between Irx3 and Irx5 in
      embryonic cardiac development and postnatal physiology.

PMID- 22992951
TI  - Sox1 marks an activated neural stem/progenitor cell in the hippocampus.
AB  - The dentate gyrus of the hippocampus continues generating new neurons throughout
      life. These neurons originate from radial astrocytes within the subgranular zone
      (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription
      factors, is expressed in a subset of radial astrocytes. Lineage tracing using
      Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells
      represent an activated neural stem/progenitor population that gives rise to most
      if not all newly born granular neurons, as well as a small number of mature hilar
      astrocytes. Furthermore, a subpopulation of Sox1-marked cells have long-term
      neurogenic potential, producing new neurons 3 months after inactivation of
      tetracycline transactivator. Remarkably, after 8 weeks of labeling and a 12-week
      chase, as much as 44% of all granular neurons in the dentate gyrus were derived
      from Sox1 lineage-traced adult neural stem/progenitor cells. The fraction of Sox1
      positive cells within the radial astrocyte population decreases with age,
      correlating with a decrease in neurogenesis. However, expression profiling shows
      that these cells are transcriptionally stable throughout the lifespan of the
      mouse. These results demonstrate that Sox1 is expressed in an activated
      stem/progenitor population whose numbers decrease with age while maintaining a
      stable molecular program.

PMID- 22992952
TI  - Maternal Cdx2 is dispensable for mouse development.
AB  - In many invertebrate and vertebrate species, cell fates are assigned through the
      cellular inheritance of differentially localized maternal determinants. Whether
      mammalian embryogenesis is also regulated by deterministic mechanisms is highly
      controversial. The caudal domain transcription factor CDX2 has been reported to
      act as a maternal determinant regulating cell fate decisions in mouse
      development. However, this finding is contentious because of reports that
      maternal Cdx2 is not essential for development. Notably, all of the previously
      published studies of maternal Cdx2 relied on injected RNA interference
      constructs, which could introduce experimental variation. Only deletion of the
      maternal gene can unambiguously resolve its requirement in mouse development.
      Here, we genetically ablated maternal Cdx2 using a Cre/lox strategy, and we
      definitively establish that maternal Cdx2 is not essential for mouse development.

PMID- 22992953
TI  - Klf4 is required for germ-layer differentiation and body axis patterning during
      Xenopus embryogenesis.
AB  - Klf4 is a transcription factor of the family of Kruppel-like factors and plays
      important roles in stem cell biology; however, its function during embryogenesis
      is unknown. Here, we report the characterization of a Klf4 homologue in Xenopus
      laevis during embryogenesis. Klf4 is transcribed both maternally and zygotically
      and the transcript is ubiquitous in embryos during germ-layer formation. Klf4
      promotes endoderm differentiation in both Nodal/Activin-dependent and 
      independent manners. Moreover, Klf4 regulates anteroposterior body axis
      patterning via activation of a subset of genes in the Spemann organizer, such as
      Noggin, Dkk1 and Cerberus, which encode Nodal, Wnt and BMP antagonists. Loss of
      Klf4 function leads to the failure of germ-layer differentiation, the loss of
      responsiveness of early embryonic cells to inducing signals, e.g. Nodal/Activin,
      and the loss of transcription of genes involved in axis patterning. We conclude
      that Klf4 is required for germ-layer differentiation and body axis patterning by
      means of rendering early embryonic cells competent to differentiation signals.

PMID- 22992955
TI  - Spatial control of flowering by DELLA proteins in Arabidopsis thaliana.
AB  - The transition from vegetative to reproductive development is a central event in
      the plant life cycle. To time the induction of flowering correctly, plants
      integrate environmental and endogenous signals such as photoperiod, temperature
      and hormonal status. The hormone gibberellic acid (GA) has long been known to
      regulate flowering. However, the spatial contribution of GA signaling in
      flowering time control is poorly understood. Here we have analyzed the effect of
      tissue-specific misexpression of wild-type and GA-insensitive (dellaDelta17)
      DELLA proteins on the floral transition in Arabidopsis thaliana. We demonstrate
      that under long days, GA affects the floral transition by promoting the
      expression of flowering time integrator genes such as FLOWERING LOCUS T (FT) and
      TWIN SISTER OF FT (TSF) in leaves independently of CONSTANS (CO) and GIGANTEA
      (GI). In addition, GA signaling promotes flowering independently of photoperiod
      through the regulation of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes in
      both the leaves and at the shoot meristem. Our data suggest that GA regulates
      flowering by controlling the spatial expression of floral regulatory genes
      throughout the plant in a day-length-specific manner.

PMID- 22992954
TI  - Activated STAT regulates growth and induces competitive interactions
      independently of Myc, Yorkie, Wingless and ribosome biogenesis.
AB  - Cell competition is a conserved mechanism that regulates organ size and shares
      properties with the early stages of cancer. In Drosophila, wing cells with
      increased Myc or with optimum ribosome function become supercompetitors that kill
      their wild-type neighbors (called losers) up to several cell diameters away.
      Here, we report that modulating STAT activity levels regulates competitor status.
      Cells lacking STAT become losers that are killed by neighboring wild-type cells.
      By contrast, cells with hyper-activated STAT become supercompetitors that kill
      losers located at a distance in a manner that is dependent on hid but independent
      of Myc, Yorkie, Wingless signaling, and of ribosome biogenesis. These results
      indicate that STAT, Wingless and Myc are major parallel regulators of cell
      competition, which may converge on signals that non-autonomously kill losers. As
      hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy,
      our results have therapeutic implications for cancer and regenerative medicine.

PMID- 22992956
TI  - Transcriptional regulatory networks in epiblast cells and during anterior neural
      plate development as modeled in epiblast stem cells.
AB  - Somatic development initiates from the epiblast in post-implantation mammalian
      embryos. Recent establishment of epiblast stem cell (EpiSC) lines has opened up
      new avenues of investigation of the mechanisms that regulate the epiblast state
      and initiate lineage-specific somatic development. Here, we investigated the role
      of cell-intrinsic core transcriptional regulation in the epiblast and during
      derivation of the anterior neural plate (ANP) using a mouse EpiSC model. Cells
      that developed from EpiSCs in one day in the absence of extrinsic signals were
      found to represent the ANP of ~E7.5 embryos. We focused on transcription factors
      that are uniformly expressed in the E6.5 epiblast but in a localized fashion
      within or external to the ANP at E7.5, as these are likely to regulate the
      epiblast state and ANP development depending on their balance. Analyses of the
      effects of knockdown and overexpression of these factors in EpiSCs on the levels
      of downstream transcription factors identified the following regulatory
      functions: cross-regulation among Zic, Otx2, Sox2 and Pou factors stabilizes the
      epiblastic state; Zic, Otx2 and Pou factors in combination repress mesodermal
      development; Zic and Sox2 factors repress endodermal development; and Otx2
      represses posterior neural plate development. All of these factors variably
      activate genes responsible for neural plate development. The direct interaction
      of these factors with enhancers of Otx2, Hesx1 and Sox2 genes was demonstrated.
      Thus, a combination of regulatory processes that suppresses non-ANP lineages and
      promotes neural plate development determines the ANP.

PMID- 22992957
TI  - Pancortins interact with amyloid precursor protein and modulate cortical cell
      migration.
AB  - Neuronal precursor cell migration in the developing mammalian brain is a complex
      process requiring the coordinated interaction of numerous proteins. We have
      recently shown that amyloid precursor protein (APP) plays a role in migration
      into the cortical plate through its interaction with two cytosolic signaling
      proteins, disabled 1 (DAB1) and disrupted in schizophrenia 1 (DISC1). In order to
      identify extracellular factors that may signal through APP to regulate migration,
      we performed an unbiased mass spectrometry-based screen for factors that bind to
      the extracellular domain of APP in the rodent brain. Through this screen, we
      identified an interaction between APP and pancortins, proteins expressed
      throughout the developing and mature cerebral cortex. Via co-immunoprecipitation,
      we show that APP interacts with all four of the mammalian pancortin isoforms
      (AMY, AMZ, BMY, BMZ). We demonstrate that the BMZ and BMY isoforms of pancortin
      can specifically reduce beta-secretase- but not alpha-secretase-mediated cleavage
      of endogenous APP in cell culture, suggesting a biochemical consequence of the
      association between pancortins and APP. Using in utero electroporation to
      overexpress and knock down specific pancortin isoforms, we reveal a novel role
      for pancortins in migration into the cortical plate. Interestingly, we observe
      opposing roles for alternate pancortin isoforms, with AMY overexpression and BMZ
      knock down both preventing proper migration of neuronal precursor cells. Finally,
      we show that BMZ can partially rescue a loss of APP expression and that APP can
      rescue effects of AMY overexpression, suggesting that pancortins act in
      conjunction with APP to regulate entry into the cortical plate. Taken together,
      these results suggest a biochemical and functional interaction between APP and
      pancortins, and reveal a previously unidentified role for pancortins in mammalian
      cortical development.

PMID- 22992959
TI  - WAG2 represses apical hook opening downstream from gibberellin and PHYTOCHROME
      INTERACTING FACTOR 5.
AB  - When penetrating the soil during germination, dicotyledonous plants protect their
      shoot apical meristem through the formation of an apical hook. Apical hook
      formation is a dynamic process that can be subdivided into hook formation,
      maintenance and opening. It has previously been established that these processes
      require the transport and signaling of the phytohormone auxin, as well as the
      biosynthesis and signaling of the phytohormones ethylene and gibberellin (GA).
      Here, we identify a molecular mechanism for an auxin-GA crosstalk by
      demonstrating that the auxin transport-regulatory protein kinase WAG2 is a
      crucial transcription target during apical hook opening downstream from GA
      signaling. We further show that WAG2 is directly activated by PHYTOCHROME
      INTERACTING FACTOR 5 (PIF5), a light-labile interactor of the DELLA repressors of
      the GA pathway. We find that wag2 mutants are impaired in the repression of
      apical hook opening in dark-grown seedlings and that this phenotype correlates
      with GA-regulated WAG2 expression in the concave (inner) side of the apical hook.
      Furthermore, wag2 mutants are also impaired in the maintenance or formation of a
      local auxin maximum at the site of WAG2 expression in the hook. WAG2 is a
      regulator of PIN auxin efflux facilitators and, in line with previous data, we
      show that this kinase can phosphorylate the central intracellular loop of all PIN
      FORMED (PIN) proteins regulating apical hook opening. We therefore propose that
      apical hook opening is controlled by the differential GA-regulated accumulation
      of WAG2 and subsequent local changes in PIN-mediated auxin transport.

PMID- 22992958
TI  - Draper acts through the JNK pathway to control synchronous engulfment of dying
      germline cells by follicular epithelial cells.
AB  - The efficient removal of dead cells is an important process in animal development
      and homeostasis. Cell corpses are often engulfed by professional phagocytes such
      as macrophages. However, in some tissues with limited accessibility to
      circulating cells, engulfment is carried out by neighboring non-professional
      phagocytes such as epithelial cells. Here, we investigate the mechanism of corpse
      clearance in the Drosophila melanogaster ovary, a tissue that is closed to
      circulating cells. In degenerating egg chambers, dying germline cells are
      engulfed by the surrounding somatic follicular epithelium by unknown mechanisms.
      We show that the JNK pathway is activated and required in engulfing follicle
      cells. We find that the receptor Draper is also required in engulfing follicle
      cells, and activates the JNK pathway. Overexpression of Draper or the JNK pathway
      in follicle cells is sufficient to induce death of the underlying germline,
      suggesting that there is coordination between the germline and follicular
      epithelium to promote germline cell death. Furthermore, activation of JNK
      bypasses the need for Draper in engulfment. The induction of JNK and Draper in
      follicle cells occurs independently of caspase activity in the germline,
      indicating that at least two pathways are necessary to coordinate germline cell
      death with engulfment by the somatic epithelium.

PMID- 22992960
TI  - Cochlin expression in vestibular endorgans obtained from patients with Meniere's
      disease.
AB  - The distribution of cochlin and its associated basement membrane proteins
      (collagen IV, collagen II, laminin-beta2, and nidogen-1) were evaluated in the
      vestibular endorgans of subjects with Meniere's disease and compared with normal
      specimens. Cochlin mRNA expression in vestibular endorgans from Meniere's disease
      specimens was also investigated. Specimens were obtained from patients who had
      Meniere's disease and who were undergoing ablative labyrinthectomy. Control
      specimens were obtained both from autopsy specimens with documented normal
      audiovestibular function and from patients undergoing labyrinthectomy for
      acoustic neuroma excision. In the normal control specimens, cochlin
      immunoreactivity was found evenly distributed in the stroma of the cristae
      ampullaris and maculae of the utricle. In Meniere's specimens, cochlin
      immunoreactivity was markedly increased; this was associated with an increase in
      cochlin mRNA expression as shown by real-time reverse transcription with the
      polymerase chain reaction. Collagen IV and laminin-beta2 immunoreactivity was
      significantly decreased in Meniere's specimens. Nidogen-1 and collagen II
      immunoreactivity was unchanged in Meniere's specimens when compared with normal
      samples. Cochlin upregulation has been implicated in the hereditary
      audiovestibulopathy, DFNA9. The increased expression of cochlin and decreased
      expression of collagen IV and laminin in Meniere's disease are suggestive that
      the overexpression of cochlin contributes to the dysfunctional inner ear
      homeostasis seen in this disease.

PMID- 22992962
TI  - Intraoperative awareness--recommendations of the Committee on Quality and Safety
      in Anaesthesia, Polish Society of Anaesthesiology and Intensive Therapy.
AB  - Modern general anaesthesia is complex and reversible.It involves a temporary loss
      of consciousness, analgesia,a decrease in muscle tension or complete muscle
      relaxation,suppressed reactions of the autonomic nervous system,and the provision
      of amnesia of events after its completion.

PMID- 22992961
TI  - Identification of KRAP-expressing cells and the functional relevance of KRAP to
      the subcellular localization of IP3R in the stomach and kidney.
AB  - KRAS-induced actin-interacting protein (KRAP), originally identified as one of
      the deregulated genes expressed in colorectal cancer, participates under
      physiological conditions in the regulation of systemic energy homeostasis and of
      the exocrine system. We have recently found that KRAP is a molecule associated
      with inositol 1,4,5-trisphosphate receptor (IP(3)R) and is critical for the
      proper subcellular localization of IP(3)R in the liver and the pancreas. However,
      the expression of KRAP and its precise function in other tissues remain elusive.
      In this study, we aimed to identify the KRAP-expressing cells in mouse stomach
      and kidneys and to examine the relevance of KRAP expression in the regulation of
      IP(3)R localization in these tissues. In the stomach, double immunohistochemical
      staining for KRAP and IP(3)R demonstrated that KRAP was expressed along with the
      apical regions in the mucous cells and the chief cells, and IP(3)R3 was
      dominantly co-localized with KRAP in these cells. Furthermore, IP(3)R2 was also
      co-localized with IP(3)R3 in the chief cells. It is of note that the proper
      localization of IP(3)R3 and IP(3)R2 in the chief cells and of IP(3)R3 in the
      mucous cells were significantly abrogated in KRAP-deficient mice. In the kidneys,
      KRAP was expressed in both the apical and the basal regions of the proximal
      tubular cells. Intriguingly, KRAP deficiency abrogated the localization of
      IP(3)R1 in the proximal tubular cells. Finally, co-immunoprecipitation study in
      the stomachs and the kidneys validated the physical association of KRAP with
      IP(3)Rs. These findings demonstrate that KRAP physically associates with IP(3)Rs
      and regulates the proper localization of IP(3)Rs in the mucous cells and the
      chief cells of the stomach and in the proximal tubular cells of the kidneys.

PMID- 22992963
TI  - Comparison of cuff-pressure changes in silicone and PVC laryngeal masks during
      nitrous oxide anaesthesia in spontaneously breathing children.
AB  - BACKGROUND: The purpose of this study was to evaluate the cuff pressures of four
      different laryngeal masks in paediatric patients undergoing routine surgery and
      to determine whether there is a substantial increase in cuff pressure when
      silicone masks are used compared to PVC laryngeal mask airways. METHODS: Hundred
      and forty patients aged < 16 yr were randomly allocated to receive one of four
      extra glottic airway devices: LMA-Classic; LMA-Unique; Soft Seal; or Cobra-PLA.
      Intracuff pressure was monitored continuously throughout the operative
      intervention. The primary outcome was measurement of an increase in cuff
      pressure. First attempt success rate, effective airway time, anatomical position
      of the airway and incidence of airway morbidity data were monitored. RESULTS:
      Mean cuff pressure increased within 5 min of N2O exposure, and was substantially
      higher in the silicone LMA-C,compared to the PVC-based extra glottic airway
      devices tested, reaching a plateau of the cuff pressure after 45 min.The overall
      first attempt success rate (97%) and the mean effective airway time (24 +/- 9
      sec) were very satisfactory and all patients underwent successful surgery.
      Anatomical position was adequate in most airways, although in 34%of the patients
      in the Cobra group herniation of either the epiglottis or arytenoids were
      detected. Airway morbidity due to the devices was insignificant. CONCLUSIONS:
      This study demonstrated a substantial increase in cuff pressure during
      anaesthesia for children in whom a silicone-based LMA-C was used, whereas PVC
      based extra glottic airway devices showed a much lower increase.

PMID- 22992964
TI  - The influence of low flow anaesthesia on renal function in cancer patients
      previously treated with nephrotoxic chemotherapeutic agents.
AB  - BACKGROUND: The aim of this study was to assess renal morbidity, associated with
      the use of low flow anaesthesia (LFA), in cancer patients previously treated with
      nephrotoxic chemotherapeutic agents. METHODS: Seventy-five patients, aged 30-70
      years, scheduled for elective surgery, were randomly allocated to three groups:
      Group A included those patients who had received nephrotoxic chemotherapeutic
      agents (cisplatin, carboplatin, methotrexate or cyclophosphamide) within 90 days
      before surgery, and who were anaesthetised with low flow (0.8(-1) L min(-1)) air
      oxygen-sevoflurane (1-3 MAC) anaesthesia; Group B included similar patients who
      received high flow (6 L min-1) anaesthesia. Non-cancer patients receiving low
      flow anaesthesia served as controls. Blood was sampled for serum creatinine, BUN,
      cistatin C, and electrolytes (Na(+), K(+), Cl(-), Ca(2+), P(3+), Mg(2+)) before
      anaesthesia, and one, three and five days after. RESULTS: There were no
      statistically significant differences between the groups. CONCLUSIONS: The use of
      low flow sevoflurane anaesthesia is not associated with an increased risk of
      nephrotoxicity in those previously exposed to nephrotoxic chemotherapeutic
      agents.

PMID- 22992965
TI  - Effect on cognition of galanthamine administered for neuromuscular block reversal
      in octogenarians undergoing cataract surgery.
AB  - BACKGROUND: The purpose of the study was to determine the possible effect of the
      cholinesterase inhibitor, galanthamine, on cognition when administered to
      antagonise neuromuscular blockade after anaesthesia. METHODS: The Wechsler Memory
      Scale was used to assess cognition before and after cataract surgery, carried out
      under general anaesthesia, in forty-five octogenarian patients. At the end of the
      operation, in order to reverse residual neuromuscular blockade, patients were
      randomly assigned to receive either galanthamine, acting on central and
      peripheral receptors, or neostigmine--a drug without central activity. RESULTS:
      The differences between the Wechsler Memory Scale scores obtained from both
      groups were not statistically significant; however, patients who received
      galanthamine experienced more side effects (e.g. nausea, vomiting, dysphoria) and
      had lower scores in memory tests performed immediately after surgery. Reduction
      of galanthamine doses did not improve the situation. CONCLUSIONS: In
      octogenarians, impaired organ function as well as changes in body composition,
      are factors which affect the pharmacodynamics and pharmacokinetics of drugs.

PMID- 22992966
TI  - Occurrence of gastrointestinal side effects associated with early use of
      commercial diets in ITU patients.
AB  - BACKGROUND: The purpose of this retrospective study was to analyse the occurrence
      of gastrointestinal side effects in enterally fed ITU patients. METHODS: We
      analysed the records of 195 ITU patients fed enterally, over at least five days,
      with commercial mixtures administered as 20-h infusions. Gastric retention, the
      number of defecations, and incidents requiring discontinuation of enteral
      feeding, were noted during the first 3 days of nutrition. RESULTS: Enteral
      nutrition was usually started during the first week of treatment (median 4,
      range: 1-33). In 118 patients receiving parenteral nutrition, the median day of
      implementing enteral feeding was day 5; some received enteral mixtures much
      earlier (day 2). The mean infusion rates of enteral mixtures were: 33 mL h-1 on
      day 1, 58 mL h-1 on day 2, and 68 mL h-1 on day 3. Gastric retention was observed
      in 49 (25.1%) patients during the first day, in 37 (19.0%) on day 2, and in 25
      (12.8%) on day 3. Discontinuation of enteral nutrition was necessary in 6
      patients due to: surgery (1), high gastric retention (4), gastrointestinal
      bleeding (1). A statistically significant correlation was found between the
      occurrence of gastric retention, infusion rates and CRP, and between the number
      of defecations and infusion rates. CONCLUSIONS: Enteral feeding with commercial
      diets is well tolerated when implemented gradually. Intolerance and the need for
      the discontinuation of enteral feeding were usually associated with a worsening
      of the patient's general condition and progression of the underlying disease.

PMID- 22992967
TI  - Independent lung ventilation for treatment of post-traumatic ARDS.
AB  - BACKGROUND: Independent lung ventilation (ILV) has been recommended for
      unilateral pulmonary pathology. We describe a case of a multiple trauma patient
      treated with ILV for unilateral lung injury. CASE REPORT: Following a road
      accident, an 18 year-old male patient was referred to the university hospital
      with multiple organ failure, a ruptured liver and spleen, a fractured spine at
      the Th1-2 level, and left lung contusion. Splenectomy and liver repair had been
      performed in a regional hospital. On admission, a left sided pneumothorax and
      haemothorax were diagnosed and an emergency thoracotomy was performed, with
      partial resection of the left lower lobe. Because of the failure of recruitment
      of the left upper lobe, the patient was intubated with a double lumen tube and
      ILV was started using a single ventilator and a prototype flow separator,
      allowing separation of volume and PEEP settings. The left lung was ventilated
      with larger volumes and a higher PEEP than the right side, resulting in rapid
      improvement of gas exchange, reduction of air leak, and a return to conventional
      ventilation within two days. The patient underwent spinal stabilisation, and was
      extubated a few days later and transferred to a rehabilitation unit. CONCLUSIONS:
      ILV with a larger tidal volume and high PEEP may be indicated in unilateral lung
      injury with a significant air leak from the injured tissue.

PMID- 22992968
TI  - Acute kidney failure complicating carbon monoxide poisoning.
AB  - BACKGROUND: Carbon monoxide, albeit common, is rarely associated with renal
      failure. We report a case of CO-associated kidney failure requiring short-term
      dialysis. CASE REPORT: A 33 year-old male was found unconscious in a bathroom
      equipped with a propane-gas heater. The duration of exposure to carbon monoxide
      was unknown. The patient was transported to a regional hyperbaric centre;the
      carboxyhaemoglobin concentration in the blood on admission was 38.3%. After 60
      min of exposure to hyperbaric oxygen, he regained consciousness and was
      transferred to the toxicology department. Mild rhabdomyolysis with acute kidney
      failure was diagnosed and despite two subsequent hyperbaric sessions,
      haemodialysis was necessary.The kidney failure resolved within two weeks, and the
      patient made a full recovery.Discussion and conclusions. Carbon monoxide mainly
      affects the central nervous system and the myocardium;renal failure may occur due
      to rhabdomyolysis and hypoxia. Therefore, all CO-poisoned patients should be
      closely monitored for their renal function.

PMID- 22992969
TI  - Fluid use in adult intensive care.
AB  - Methods for the restoration of circulating blood volume, including the use of
      intravenous fluids, have been widely discussed over many years. There are no
      clear guidelines regarding the type of solutions, the total volume that should be
      transfused, or time schedules. Colloid solutions, usually hydroxyethyl starch
      compositions, are probably the most commonly used volume expanders in
      resuscitation, despite the lack of convincing trials and possible
      nephrotoxicity.In 2012, a task force of ESICM published a consensus statement on
      colloid use in critically ill adult patients. They stressed that infusion of an
      inappropriate volume may worsen the outcome of critically ill patients. Static
      parameters of cardiac filling volume, such as CVP or PCWP, commonly used in
      clinical practice, were found to be useless in the prediction of fluid
      responsiveness; volumetric or dynamic parameters, like global end diastolic
      volume (GEDV) or stroke volume variations (SVV), obtained by PICCO meters, seemed
      be much more appropriate. The dynamic fluid challenge test, which is transfusion
      of approx. 200 cc (or 3 mL kg-1) of any fluid over 5-10 min resulting in an
      increase of stroke volume, has also been recommended for the identification of
      those patients who may benefit from fluid resuscitation. The old passive leg
      raising test can also be used for this purpose.Despite prolonged discussion about
      fluid therapy in specific groups of critically ill patients, there is no
      convincing data to indicate the superiority of colloids over crystalloids. The
      choice of fluids is usually based on personal preference and hospital policy.
      Among crystalloid solutions, balanced preparations such as acetates, lactates,
      malates or citrates are recommended to avoid hyperchloraemia, a common side
      effect of saline infusion. There is no agreement regarding colloid solutions.The
      fluid transfusion regimen in critically ill patients should therefore be based on
      clinical assessment and patient responses.

PMID- 22992970
TI  - Strategies of empiric antibiotic therapy in severe sepsis.
AB  - Severe sepsis and septic shock remain the leading causes of multiple organ
      failure and mortality in surgical intensive care units. Early antibiotic therapy
      recently became a challenge, because of the increased number of infections caused
      by multiple drug resistant bacteria, with Gram-negative bacteria such as
      Klebsiella pneumoniae and Pseudomonas aeruginosa being the most frequently
      cultured pathogens.In this review, detailed recommendations for the treatment of
      various infections are presented and discussed, with particular emphasis on the
      determination of empiric antibiotic therapy in the early stages of sepsis and
      localised infections.

PMID- 22992971
TI  - Anaphylactic reactions during anaesthesia and the perioperative period.
AB  - Allergy and hypersensitivity occurring during anaesthesia remains a major cause
      of concern for anaesthesiologists.Drugs administered during surgery and various
      anaesthetic procedures can elicit two major groups of adverse reactions. The
      first group includes reactions that are usually dose-dependent and related to the
      pharmacological properties of a drug and/or its metabolites. The remaining
      reactions are mostly related to hypersensitivity and allergic responses. They do
      not depend on specific pharmacology and are usually not dose
      dependent.Anaphylaxis is among the most severe of immune-mediated reactions; it
      generally occurs following re-exposure to specific antigens and release of
      proinflamatory mediators. The commonest drugs responsible for intraoperative
      anaphylaxis are muscle relaxants, but latex also accounts for a significant
      number of incidents, and the frequency of intraoperative latex anaphylactic
      reactions is increasing. Multiple organ failure, beginning with bronchospasm and
      cardiovascular collapse, is typical of latex reactions. An increased serum
      tryptase concentration confirms the diagnosis of an anaphylactic reaction, and
      triggers can be identified by skin prick, intradermal injection, or serologic
      testing.The elimination of triggers during subsequent medical episodes is
      essential to avoid major mortality and morbidity.

PMID- 22992972
TI  - Coronary air embolism.
AB  - The case report of acute coronary episode caused by air embolism associated with
      the removal of central vascular access, published in "Anaesthesiology Intensive
      Therapy"1/2012 aroused much interest [1]. Iatrogenic gas emboli are rare, albeit
      dramatic complications of therapeutic interventions,which result in persistent
      neurological symptoms in over 40% of cases [2].

PMID- 22992974
TI  - ENTPD5-mediated modulation of ATP results in altered metabolism and decreased
      survival in gliomablastoma multiforme.
AB  - Gliomablastoma multiforme (GBM) is the most aggressive of brain cancers in
      humans. Response to current therapies remains extremely poor, with dismal
      survival statistics. Recently, the endoplasmic reticulum UDPase, ectonucleoside
      triphosphate diphosphohydrolase 5 (ENTPD5), was identified as a key component in
      the Akt/phosphatidylinositol 3-kinase/phosphatase and tensin homolog regulatory
      loop, capable of synergizing aerobic glycolysis and cancer cell proliferation in
      vitro. Utilizing a novel enhanced acceptor fluorescence-based single-cell
      adenosine 5'-triphosphate (ATP) biosensor, we analyzed ENTPD5-mediated modulation
      of cytosolic ATP. Here, ENTPD5-dependent modulation of cellular ATP in GBM
      results in altered metabolic kinetics in vitro, increasing the catabolic
      efficiencies of aerobic glycolysis and fatty acid oxidation. Additionally, an
      upregulation of ENTPD5 in both GBM mouse xenografts and in GBM patient tumors was
      identified, resulting in dramatically reduced survival. Therefore, these results
      not only provide new tools to monitor ATP flux and cellular metabolism kinetics
      but also identified a novel therapeutic target for GBM.

PMID- 22992976
TI  - Emodin induces Panc-1 cell apoptosis via declining the mitochondrial membrane
      potential.
AB  - In this study, we investigated the apoptotic effect of emodin on human pancreatic
      cancer cell line Panc-1 in vitro and in vivo as well as the possible mechanisms
      involved. In vitro, human pancreatic cancer cell line Panc-1 was exposed to
      varying concentrations of emodin (0, 10, 20, 40 or 80 umol/l). Then the
      mitochondrial membrane potential (MMP) was analyzed by JC-1 staining, cell
      apoptosis was analyzed by flow cytometry (FCM) and cell proliferation was
      analyzed by MTT. In vivo, nude mice orthotopically implanted were randomly
      divided into five groups to receive treatments by different doses of emodin:
      control group (normal saline 0.2 ml), E10 group (emodin 10 mg/kg), E20 group
      (emodin 20 mg/kg), E40 group (emodin 40 mg/kg) and E80 group (emodin 80 mg/kg).
      Each mouse was treated 5 times by intraperitoneal injection of emodin every 3
      days. During the treatment, the feeding stuff was recorded. One week after the
      last treatment, we recorded the body weight and the maximum diameter of tumor in
      each group before the mice were sacrificed. Then the cell apoptosis of the tumor
      was tested by TUNEL assay. The results in vitro showed that the MMP of the cells
      declined and the apoptosis rate increased with the emodin concentration
      increasing and the cell proliferation of each group was inhibited in a dose- and
      time-dependent manner by emodin. The feeding stuff curve did not decline
      significantly in E40 group and the apoptosis rate of the tumor cells in this
      group was higher than the lower-dose groups. Taken together, our results
      demonstrate that emodin may induce the pancreatic cancer cell apoptosis via
      declining the MMP and a moderate dose of emodin improved the living state of the
      model mice.

PMID- 22992975
TI  - Structural and functional maturation of active zones in large synapses.
AB  - Virtually all functions of the nervous system rely upon synapses, the sites of
      communication between neurons and between neurons and other cells. Synapses are
      complex structures, each one comprising hundreds of different types of molecules
      working in concert. They are organized by adhesive and scaffolding molecules that
      align presynaptic vesicular release sites, namely, active zones, with
      postsynaptic neurotransmitter receptors, thereby allowing rapid and reliable
      intercellular communication. Most synapses are relatively small, and acting alone
      exerts little effect on their postsynaptic partners. Some, however, are much
      larger and stronger, reliably driving the postsynaptic cell to its action
      potential threshold, acting essentially as electrical relays of excitation. These
      large synapses are among the best understood, and two of these are the subject of
      this review, namely, the vertebrate neuromuscular junction and the calyx of Held
      synapse in the mammalian auditory pathway of the brain stem. Both synapses
      undergo through a complex and well-coordinated maturation process, during which
      time the molecular elements and the biophysical properties of the secretory
      machinery are continuously adjusted to the synapse size and to the functional
      requirements. We here review the morphological and functional changes occurring
      during postnatal maturation, noting particular similarities and differences
      between these two large synapses.

PMID- 22992977
TI  - Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest
      in the G0/G1 phase and apoptosis in U87 human glioma cells.
AB  - The Ezh2 gene is an important member of the polycomb-group (PcG) family. As a
      newly identified oncogene, the expression of Ezh2 has been shown to be
      significantly increased in prostate cancer, breast cancer, renal cell carcinoma
      and hepatic cancer; however, a role for Ezh2 in the occurrence of glioma has not
      yet been reported. In this study, we found that the Ezh2 gene is highly expressed
      in U87 human glioma cells. Using RNA interference, we demonstrated that the
      downregulation of Ezh2 expression in U87 human glioma cells resulted in apoptosis
      and a cell cycle arrest in the G0/G1 phase. In addition, we found that silencing
      of the Ezh2 gene altered the mitochondrial membrane potential and promoted the
      release of cytochrome c from the mitochondria. Furthermore, the reduced
      expression of Ezh2 altered the Bax and Bcl-2 protein levels and led to the
      activation of caspase 9 and 3. These results indicate that the apoptosis induced
      in U87 human glioma cells by the silencing of the Ezh2 gene is related to the
      mitochondrial pathway.

PMID- 22992978
TI  - Neurabin: a key factor in the specific neuroprotection mediated by Adenosine.

PMID- 22992980
TI  - Flow cytometric immunophenotyping is of great value to diagnosis of natural
      killer cell neoplasms involving bone marrow and peripheral blood.
AB  - Natural killer (NK) cell neoplasms are unusual disorders. In this study we
      compared results of flow cytometric immunophenotype (FCI) with cytomorphology,
      histopathology and clinical findings in a series of patients with NK cell
      neoplasms with peripheral blood and/or bone marrow involvement, and the FCI of
      neoplastic and normal NK cells were compared. Retrospective data and specimens
      (bone marrow aspiration or peripheral blood) from 71 cases of NK cell neoplasms
      were obtained. All patients have been demonstrated laboratory and clinical
      features consistent with NK cell neoplasms, and the subtypes were determined by
      integrated clinical estimation. Routine 4-color flow cytometry (FCM) using a NK/T
      cell related antibody panels was performed. NK cell neoplasms were divided into
      two major subtypes by FCI, namely malignant NK cell lymphoma, including
      extranodal nasal type NK cell lymphoma (ENKL, 11 cases) and aggressive NK cell
      lymphoma/leukemia (ANKL, 43 cases), and relative indolent chronic
      lymphoproliferative disorder of NK cell (CLPD-NK, 17 cases). The former exhibited
      stronger CD56-expressing, larger forward scatter (FSC) and more usually CD7- and
      CD16-missing. FCI of CLPD-NK was similar to normal NK cells, but CD56-expressing
      was abnormal, which was negative in five cases and partially or dimly expressed
      in eight cases. Cytomorphologic abnormal cells were found on bone marrow slides
      of 4 cases of ENKL and 30 cases of ANKL. Eight cases of ENKL were positive in
      bone marrow biopsies, and other three cases were negative. In 32 cases of ANKL
      which bone marrow biopsies were applied, 21 cases were positive in the first
      biopsies. Lymphocytosis was found only in six cases of CLPD-NK by cytomorphology,
      and biopsy pathology was not much useful for diagnosing CLPD-NK. These results
      suggest that FCM analysis of bone marrow and peripheral blood was superior to
      cytomorphology, bone marrow biopsy, and immunohistochemistry in sensitivity and
      early diagnosis for ANKL, stage III/IV ENKL and CLPD-NK. FCI could not only
      define abnormal NK cells but also determine the malignant classification. It is
      beneficial for clinical management and further study of NK cell neoplasms.

PMID- 22992979
TI  - A miniaturized transcutaneous system for continuous glucose monitoring.
AB  - Implantable sensors for continuous glucose monitoring hold great potential for
      optimal diabetes management. This is often undermined by a variety of issues
      associated with: (1) negative tissue response; (2) poor sensor performance; and
      (3) lack of device miniaturization needed to reduce implantation trauma. Herein,
      we report our initial results towards constructing an implantable device that
      simultaneously address all three aforementioned issues. In terms of device
      miniaturization, a highly miniaturized CMOS (complementary metal-oxide
      semiconductor) potentiostat and signal processing unit was employed (with a
      combined area of 0.665 mm(2)). The signal processing unit converts the current
      generated by a transcutaneous, Clark-type amperometric sensor to output frequency
      in a linear fashion. The Clark-type amperometric sensor employs stratification of
      five functional layers to attain a well-balanced mass transfer which in turn
      yields a linear sensor response from 0 to 25 mM of glucose concentration, well
      beyond the physiologically observed (2 to 22 mM) range. In addition, it is coated
      with a thick polyvinyl alcohol (PVA) hydrogel with embedded poly(lactic-co
      glycolic acid) (PLGA) microspheres intended to provide continuous, localized
      delivery of dexamethasone to suppress inflammation and fibrosis. In vivo
      evaluation in rat model has shown that the transcutaneous sensor system
      reproducibly tracks repeated glycemic events. Clarke's error grid analysis on the
      as-obtained glycemic data has indicated that all of the measured glucose readings
      fell in the desired Zones A & B and none fell in the erroneous Zones C, D and E.
      Such reproducible operation of the transcutaneous sensor system, together with
      low power (140 MUW) consumption and capability for current-to-frequency
      conversion renders this a versatile platform for continuous glucose monitoring
      and other biomedical sensing devices.

PMID- 22992981
TI  - Paraneoplastic disseminated lentigines heralding aggressive Langerhans cell
      sarcoma.

PMID- 22992982
TI  - Short- and long-term effects of various Citrullus colocynthis seed extracts in
      normal and streptozotocin-induced diabetic rats.
AB  - In the light of previous findings, the major aim of the present study was to
      investigate the potential beneficial effects of various Citrullus colocynthis L.
      seed extracts on such variables as glucose tolerance, body weight gain, pancreas,
      liver, kidney, testis, epididymal fat and diaphragm muscle weight, as well as
      serum cholesterol, triglyceride, urea, creatinine, transaminases and alkaline
      phosphatase concentrations in an animal model of type-1 diabetes mellitus, i.e.
      streptozotocin-induced diabetic rats. For purpose of comparison, a comparable
      study was conducted in normal rats. Both the immediate and long-term effects of
      the plant extracts were assessed in rats injected daily, up to 3 weeks after the
      start of the experiments. The results of this study reinforce the view that both
      a crude aqueous extract and a n-butanol extract from the Citrullus colocynthis L.
      seeds may represent the best candidates in order to eventually identify a
      component suitable for the treatment of both type-1 and type-2 diabetic subjects.

PMID- 22992983
TI  - Indications for use and safety of rituximab in childhood renal diseases.
AB  - Rituximab was initially developed for the treatment of patients with B cell
      lymphoma but has during the last decade proven to be quite effective in treating
      a range of kidney diseases including lupus nephritis, nephrotic syndrome, and
      also in different situations before and after a renal transplant. We will here
      review the scientific basis for the use of rituximab in children with renal
      diseases and give recommendations both regarding its clinical use and need for
      further research.

PMID- 22992984
TI  - Refractory hypotension after bilateral nephrectomies in a Denys-Drash patient
      with phenylketonuria.
AB  - BACKGROUND: Denys-Drash (DDS) syndrome is a rare genetic syndrome resulting from
      a mutation in the Wilms' tumor suppressor gene 1 (WT1), which presents with early
      onset nephrotic syndrome progressing rapidly to end-stage kidney disease (ESKD),
      pseudohermaphroditism, and high rates of Wilms' tumor. CASE-DIAGNOSIS/TREATMENT:
      We present the case of an infant born with DDS and phenylketonuria with neonatal
      ESKD and dependence on peritoneal dialysis (PD). This patient developed
      refractory hypotension after elective bilateral nephrectomies at 10 months of
      age. Despite outpatient management with sodium supplements and changes in PD
      fluid removal, the patient was hospitalized for refractory post-prandial
      hypotension with concurrent lactic acidosis. Blood pressure control and feeding
      tolerance was achieved using intermittent doses of midodrine, an oral alpha
      adrenergic agonist. CONCLUSIONS: We discuss this case to offer a therapeutic
      option for the rare occurrence of persistent post-nephrectomy hypotension.

PMID- 22992985
TI  - Hypoxia downregulates the expression of cell surface MICA without increasing
      soluble MICA in osteosarcoma cells in a HIF-1alpha-dependent manner.
AB  - Tumor cells express NKG2D ligands on their cell surface, which are the ligands of
      the activating receptor, NKG2D, that is expressed on the surface of NK cells. The
      binding of NK cells to tumor cells through the interaction of NKG2D and its
      ligands induces the cytolysis of the tumor cells. In the present study, we
      investigated the effects of hypoxia on the expression of NKG2D ligands on the
      surface of human osteosarcoma cells using three cell lines. To produce hypoxic
      and normoxic conditions, the osteosarcoma cell lines were cultured under 1 and
      20% O2 conditions, respectively. The osteosarcoma cells expressed NKG2D ligands
      such as MHC class I-related chain molecules A and B (MICA and MICB) and the UL16
      binding proteins 1, 2 and 3 (ULBP 1, 2 and 3). MICA was the most frequently
      expressed NKG2D ligand in the osteosarcoma cells. Hypoxia decreased the
      expression of cell surface MICA only without increasing the secretion of soluble
      MICA, which is produced by proteolytic cleavage of cell surface MICA. Hypoxia
      consistently decreased the susceptibility of the osteosarcoma cells to the
      cytotoxicity of the NK cells. Hypoxia induced the expression of hypoxia-inducible
      factor-1alpha (HIF-1alpha), and knockdown of the expression of HIF-1alpha using
      small interfering RNA increased the expression of cell surface MICA and
      concomitantly increased the level of soluble MICA. Hypoxia decreased the
      production of nitric oxide (NO) metabolites (nitrite and nitrate), thus,
      indicating a decreasing effect on NO production. However, a NO donor, NOC18,
      decreased the expression of cell surface MICA without any apparent effects on the
      expression of HIF-1alpha under both hypoxic and normoxic conditions. The present
      results indicate that hypoxia downregulates the expression of cell surface MICA
      without increasing the level of soluble MICA in a HIF-1alpha-dependent manner and
      suggest that the effects of hypoxia are not linked to the hypoxia-induced
      reduction of NO production.

PMID- 22992986
TI  - SAGE analysis highlights the putative role of underexpression of ribosomal
      proteins in GH-secreting pituitary adenomas.
AB  - BACKGROUND: Although the molecular pathogenesis of pituitary adenomas has been
      assessed by several different techniques, it still remains partially unclear.
      Ribosomal proteins (RPs) have been recently related to human tumorigenesis, but
      they have not yet been evaluated in pituitary tumorigenesis. OBJECTIVE: The aim
      of this study was to introduce serial analysis of gene expression (SAGE), a high
      throughput method, in pituitary research in order to compare differential gene
      expression. METHODS: Two SAGE cDNA libraries were constructed, one using a pool
      of mRNA obtained from five GH-secreting pituitary tumors and another from three
      normal pituitaries. Genes differentially expressed between the libraries were
      further validated by real-time PCR in 22 GH-secreting pituitary tumors and in 15
      normal pituitaries. RESULTS: Computer-generated genomic analysis tools identified
      13,722 and 14,993 exclusive genes in normal and adenoma libraries respectively.
      Both shared 6497 genes, 2188 were underexpressed and 4309 overexpressed in
      tumoral library. In adenoma library, 33 genes encoding RPs were underexpressed.
      Among these, RPSA, RPS3, RPS14, and RPS29 were validated by real-time PCR.
      CONCLUSION: We report the first SAGE library from normal pituitary tissue and GH
      secreting pituitary tumor, which provide quantitative assessment of cellular
      transcriptome. We also validated some downregulated genes encoding RPs.
      Altogether, the present data suggest that the underexpression of the studied RP
      genes possibly collaborates directly or indirectly with other genes to modify
      cell cycle arrest, DNA repair, and apoptosis, leading to an environment that
      might have a putative role in the tumorigenesis, introducing new perspectives for
      further studies on molecular genesis of somatotrophinomas.

PMID- 22992987
TI  - Effects of agricultural pesticides on the health of Rana pipiens frogs sampled
      from the field.
AB  - There is evidence that over the last 30 years, there have been mass declines in
      diverse geographic locations among amphibian populations due to disease
      outbreaks. Multiple causes have been suggested to explain this increase in
      disease incidence. Among these, climate changes, environmental pollution and
      reduced water quality are gaining attention. Indeed, some chemicals of
      environmental concerns are known to alter the immune system. It is possible that
      exposure to these pollutants could alter the immune system of anurans and render
      them more susceptible to different pathogens. In this study, we sampled Rana
      pipiens in five different sites near St. Lawrence River (Quebec, Canada) during
      the months of July and September in 2001. Two of these sites were protected
      areas, in which low levels of pesticides were detected, while the remaining three
      sites were located in areas with intensive corn and soybeans cultivations. Our
      results demonstrated that frogs living in agricultural regions are smaller in
      size and weight than frogs living in areas with lower levels of pesticides at
      both sampling times. Moreover, we have observed a significant decrease in the
      number of splenocytes (cellularity) and the phagocytic activity in frogs sampled
      in impacted sites. Taken together, these results suggest that frogs living in
      agricultural regions might be more vulnerable to infections and diseases through
      their smaller size and alteration of their immune system. Our results also
      contribute to the overall discussion on factors involved in amphibian declines.

PMID- 22992988
TI  - Moderate phosphorus application enhances Zn mobility and uptake in
      hyperaccumulator Sedum alfredii.
AB  - While phytoextraction tools are increasingly applied to remediation of
      contaminated soils, strategies are needed to optimize plant uptake by improving
      soil conditions. Mineral nutrition affects plant growth and metal absorption and
      subsequently the accumulation of heavy metal through hyper-accumulator plants.
      Microcosm experiments were conducted in greenhouse to examine the effect of
      different phosphorus (P) sources on zinc (Zn) phytoextraction by Sedum alfredii
      in aged Zn-contaminated paddy soil. The Zn accumulation, soil pH, microbial
      biomass and enzyme activity, available Zn changes. and Zn phytoremediation
      efficiency in soil after plant harvest were determined. Upon addition of P, Zn
      uptake of S. alfredii significantly increased. Mehlich-3 extractable or the
      fractions of exchangeable and carbonate-bound soil Zn were significantly
      increased at higher P applications. Soil pH significantly decreased with
      increasing P application rates. Soil microbial biomass in the P-treated soils was
      significantly higher (P < 0.05) than those in the control. Shoot Zn concentration
      was positively correlated with Mehlich-3 extractable P (P < 0.0001) or
      exchangeable/carbonate-bound Zn (P < 0.001), but negatively related to soil pH (P
      < 0.0001). These results indicate that application of P fertilizers has the
      potential to enhance Zn mobility and uptake by hyperaccumulating plant S.
      alfredii, thus increasing phytoremediation efficiency of Zn-contaminated soils.

PMID- 22992990
TI  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis in a young Lebanese girl.
AB  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently recognized
      autoimmune neurologic disorder that presents with severe neuropsychiatric
      symptoms in previously healthy children. A 4-year-old Lebanese girl presented
      with new-onset behavioral changes, orofacial dyskinesias, fluctuation in
      consciousness, inability to walk, and mutism. Antibodies directed against NMDA
      receptors were detected in the patient's serum and cerebrospinal fluid. Prompt
      treatment with a single course of intravenous immunoglobulin resulted in early
      complete recovery. This is the first case report of a Middle Eastern child
      affected with this condition.

PMID- 22992991
TI  - Vanishing White Matter With Hepatomegaly and Hypertriglyceridemia Attacks.
AB  - Vanishing white matter disease is one of the most prevalent leukodystrophies in
      childhood. It is caused by mutations in any of the genes encoding the 5 subunits
      of the eukaryotic translation initiation factor 2B (eIF2B), EIF2B1 through
      EIF2B5. Phenotypic variation is wide and it may affect people of all ages. Here
      we present a child with vanishing white matter who had hepatomegaly and
      hypertriglyceridemia attacks along with neurologic deterioration episodes. He was
      found heterozygous for the 2 mutations c.817 A>C, p.Lys273Gln and c.939_948del,
      p.Asp314ProfsX23 in the gene EIF2B2. Until today, this association was not
      defined in the literature.

PMID- 22992992
TI  - Anthocyanins in the black soybean (Glycine max L.) protect U2OS cells from
      apoptosis by inducing autophagy via the activation of adenosyl monophosphate
      dependent protein kinase.
AB  - Anthocyanins (ATCs) have been reported to induce apoptosis in various types of
      cancer cells, stimulating the development of ATCs as a cancer chemotherapeutic or
      chemopreventive agent. It was recently reported that ATCs can induce autophagy,
      however, the mechanism for this remains unclear. In the present report, we
      carried out mechanistic studies of the mechanism involved in ATC-induced
      autophagy using ATCs extracted from black soybeans (cv. Cheongja 3, Glycine max
      L.). ATCs clearly induced hallmarks of autophagy, including LC3 puncta formation
      and the conversion of LC3-I to LC3-II in U2OS human osteosarcoma cells. The
      induction of autophagy was accompanied by the phosphorylation of multiple protein
      kinases including extracellular signal-regulated kinase (ERK)1/2, p38 mitogen
      activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), protein kinase B
      (AKT) and adenosyl mono-phosphate-dependent protein kinase (AMPK). While chemical
      inhibitors against ERK1/2, p38 MAPK, JNK and AKT failed to inhibit ATC-induced
      autophagy, the suppression of AMPK by compound C (CC) as well as siRNA against
      AMPK reduced ATC-induced autophagy. The treatment of ATCs resulted in a decrease
      in intracellular ATP contents and the activation of AMPK by AICAR treatment also
      induced autophagy. It is noteworthy that the reduction of autophagy via the
      inhibition of AMPK resulted in enhanced apoptosis in ATC-treated cells. In
      addition, siRNA against forkhead box O3A (FOXO3a), a downstream target of AMPK,
      suppressed ATC-induced autophagy and p27KIP1 siRNA increased apoptosis in ATC
      treated cells. Collectively, it can be concluded that ATCs induce autophagy in
      U2OS cells via activation of the AMPK-FOXO3a pathway and protect cells from ATC
      induced apoptosis via the AMPK-p27KIP1 pathway. These results also suggest that
      autophagy-modulating agents could contribute to the efficient development of ATCs
      as anticancer therapy.

PMID- 22992993
TI  - May dual-source computed tomography angiography replace invasive coronary
      angiography in the evaluation of patients referred for valvular disease surgery?
AB  - BACKGROUND: Coronary computed tomography (CT) angiography is currently the only
      alternative to invasive angiography in the evaluation of coronary anatomy. In
      patients referred for valvular or thoracic aortic disease surgery, invasive
      coronary angiography remains the gold standard required by cardiac surgeons
      during the preoperative evaluation. According to the current European Society of
      Cardiology guidelines, evaluation of coronary anatomy is recommended in all
      patients above 40 years of age, with a history of coronary artery disease (CAD),
      in postmenopausal women, patients with left ventricular systolic dysfunction,
      with suspected ischaemic aetiology of mitral regurgitation, and in patients with
      one or more risk factors for CAD. The possibility to perform coronary CT
      angiography to exclude CAD before planned non-coronary cardiac surgery was first
      allowed in the 2010 Report of the American College of Cardiology Foundation Task
      Force on Expert Consensus. AIM: To evaluate the usefulness of dual-source CT for
      the evaluation of coronary anatomy in patients before planned cardiac valvular
      surgery. METHODS: We studied 98 consecutive patients with a haemodynamically
      significant valvular heart disease and guideline-based indications for coronary
      angiography to exclude CAD before planned valvular surgery. Exclusion criteria
      included cardiac arrhythmia (atrial fibrillation, frequent ventricular and
      supraventricular premature beats), estimated glomerular filtration rate < 60
      mL/min/1.73 m(2), allergy to iodine contrast agents, and lack of patient consent.
      Mean patient age was 58.8 (range 30-78) years. Coronary artery calcium score
      (CACS) was first determined in all patients. Coronary CT angiography was not
      performed if CACS was > 1000. In the remaining patients, complete CT evaluation
      was performed with the administration of a contrast agent. Conventional invasive
      coronary angiography was subsequently performed in patients with at least one >
      50% stenosis, artifacts due to calcifications, or motion artifacts. RESULTS: In
      79 (80.6%) patients, CT angiography excluded the presence of a significant
      coronary artery stenosis without the need for invasive angiography. Conventional
      coronary angiography was required in 19 (19.4%) patients, including 13 (13.3%)
      patients with a > 50% stenosis in CT angiography, 2 (2%) patients with
      calcification artifacts, 1 (1%) patient with motion artifacts, 2 (2%) patients
      with CACS > 1000 in whom CT angiography was nor performed, and 1 (1%) patient
      with allergic symptoms during administration of a test dose of the contrast
      agent. Ultimately, significant CAD was diagnosed in 9 (9.2%) patients in whom
      coronary artery bypass surgery was also performed. In addition, vascular
      anomalies were diagnosed with cardiac CT angiography in 5 (5.1%) patients. In 14
      patients, CT angiography was also used for previously planned evaluation of a
      coexisting aortic aneurysm. CONCLUSIONS: Coronary CT angiography may be useful to
      exclude significant CAD in patients referred for valvular disease surgery.

PMID- 22992994
TI  - Effects of biventricular pacing on right ventricular function assessed by
      standard echocardiography.
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the short term effect
      of cardiac resynchronisation therapy (CRT) on right ventricular (RV) function
      assessed by standard echocardiography. METHODS: Data from 57 patients (54 men,
      95%; three women, 5%), aged 66.4 +/- 8.7 years with heart failure (HF) was
      analysed. All patients were in NYHA III-IV functional classes, despite optimal
      pharmacological treatment according to the current guidelines, had left
      ventricular ejection fraction <= 35% and QRS complex >= 120 ms in a standard
      electrocardiogram. At baseline and three months after CRT implantation the
      patients' histories were taken, an anthropometrical examination was made,
      laboratory tests including the level of NT-proBNP and electrocardiogram were
      performed, and echocardiographic examination was extended by tissue Doppler
      imaging techniques and complex RV evaluation. RESULTS: Three months after CRT
      implantation in the whole study group, the average NYHA functional class had
      decreased from 3.11 +/- 0.28 to 2.25 +/- 0.68 (p < 0.001), and the six-minute
      walk test distance had increased from 298.04 +/- 107.42 m to 373.12 +/- 127.15 m
      (p < 0.001). CRT improved RV systolic function in the whole study group.
      Tricuspid annular plane systolic excursion had increased from 13.95 +/- 2.80 to
      15.79 +/- 2.33 mm (p < 0.001), and so likewise had systolic excursion velocity
      (S'), which rose from 8.84 +/- 3.45 to 11.00 +/- 3.43 cm/s (p < 0.001). Tricuspid
      regurgitation grade decreased from 2.02 +/- 0.95 to 1.86 +/- 0.91 (p = 0.013). RV
      systolic pressure decreased from 31.07 +/- 20.43 to 27.75 +/- 17.35 mm Hg (p <
      0.001). RV fractional area change rose from 31.35 +/- 10.30% to 35.40 +/- 10.51%
      (p < 0.001). CONCLUSIONS: This study showed that CRT improved RV systolic
      function evaluated with parameters assessed in standard echocardiographic
      examination three months after therapy initiation. The observed improvement was
      consistent among all applied echocardiographic parameters reflecting RV systolic
      function.

PMID- 22992995
TI  - [Right ventricle in CRT - complicate what is simple, or simplify what is
      complicated?].

PMID- 22992996
TI  - Quality of life in patients after minimally invasive endoscopic atraumatic
      coronary artery bypass grafting: a long-term follow-up.
AB  - BACKGROUND: Quality of life (QoL) is an acknowledged parameter that subjectively
      describes treatment effectiveness and is used also in cardiac surgery. Minimally
      invasive totally endoscopic atraumatic coronary artery bypass grafting (EACAB)
      does not require the use of cardiopulmonary bypass, reduces hospital stay and
      facilitates early rehabilitation. Therefore, this procedure should significantly
      improve QoL in patients with coronary artery disease. AIM: To assess QoL during a
      12-year follow-up in patients who underwent EACAB. METHODS: The study group
      comprised 706 consecutive patients who underwent EACAB between April 1998 and
      December 2010. Median duration of follow-up was 1918 days. QoL was assessed by
      either telephone interview or letter correspondence. Complete data were obtained
      from 413 persons aged 59 +/- 6 years. We evaluated the effect of pre- and
      postoperative variables on QoL. RESULTS: Compared with the preoperative period, a
      marked improvement in QoL after EACAB was reported by 38.6%, and improvement by
      37.2% of patients. No change in QoL was noted by 18.8% of subjects, and 5.4% of
      responders reported deterioration of QoL. The following parameters were found to
      have no impact on QoL: gender (p = 0.3), myocardial infarction (MI) before EACAB
      (p = 0.3), diabetes mellitus (p = 0.7), and baseline angina severity by the
      Canadian Cardiovascular Society (CCS) classification (p = 0.8). Time delay
      between the surgery and QoL assessment had no impact on the results. During the
      follow-up, reported QoL was related to the severity of angina symptoms (p =
      0.006), need for rehospitalisation (p = 0.02), MI (p = 0.04) and repeated
      revascularisation (p = 0.02). In multivariate analysis, only MI had a significant
      impact on QoL (p = 0.04). Current drug therapy had no impact on QoL. CONCLUSIONS:
      EACAB significantly improved QoL in coronary patients. MI during follow-up was
      associated with deterioration of QoL.

PMID- 22992997
TI  - Homocysteine concentration and the risk of death in the adult Polish population.
AB  - BACKGROUND: Although there is a considerable epidemiologic evidence for a
      relation between homocysteine (Hcy) level and cardiovascular disease (CVD). The
      role of Hcy as a causal risk factor remains controversial. AIM: To determine
      associations between Hcy level and all-cause and cardiovascular mortality in
      general population of Poland. METHODS: Within the frame of the National
      Multicenter Health Survey (WOBASZ), a representative sample of whole Polish
      population aged 20-74 was screened in years 2003-2005 and prospectively followed
      up until 2009. Baseline determinations, among other classical risk factors,
      included Hcy level in 7165 responders, performed by an immunoenzymatic method
      using IMMULITE 1 analyser and DPC reagents. Survival rates were followed up until
      2009 and average follow up time was 5.4 years. RESULTS: During the 38,818.9
      person-years of follow-up there were 270 deaths including 108 due to CVD, 37 due
      to coronary heart disease and 21 due to stroke. The relative risk of all-cause
      and CVD mortality was significantly higher in the highest (> 10.51 MUmol/L)
      compared to the lowest (< 8.20 MUmol/L) Hcy tercile in crude and multivariable
      proportional hazards models adjusted for sex, age, smoking status, hypertension,
      body mass index, total cholesterol, glucose and high sensitivity-C-reactive
      protein. Hazards ratios (95% confidence intervals) were as follows: all-cause
      mortality HR (95% CI): crude = 4.528 (2.947-6.154), multivariable-adjusted =
      1.766 (1.197-2.605), CVD mortality crude = 4.322 (2.426-7.700), multivariable- 
      adjusted = 1.937 (1.051-3.569). CONCLUSIONS: In Polish adult population Hcy
      concentration is independently associated with all-cause and CVD mortality.

PMID- 22992998
TI  - Increased epicardial adipose tissue in patients with slow coronary flow
      phenomenon.
AB  - BACKGROUND: Slow coronary flow (SCF) is an angiographic finding characterised by
      delayed opacification of epicardial coronary arteries without obstructive
      coronary disease. Epicardial adipose tissue (EAT), localised beneath the visceral
      pericardium, is a metabolically active endocrine and paracrine organ with
      possible interactions within the heart. EAT and low-grade inflammation play major
      roles in the atherosclerotic vascular processes and may be important in other
      coronary pathologies such as SCF. AIM: To investigate whether EAT and C-reactive
      protein (CRP) are increased in patients with isolated SCF compared to normal
      subjects. METHODS: The present study was cross-sectional and observational,
      consisting of 66 individuals who underwent coronary angiography with a suspicion
      of coronary artery disease and who had angiographically normal coronary arteries
      of varying coronary flow rates. The relationship between EAT, CRP and SCF
      phenomenon was investigated. Thirty-three patients with isolated SCF (mean age:
      56 +/- 10 years) and 33 age- and gender-matched control participants with normal
      coronary flow (NCF), but without SCF, (mean age: 55 +/- 10 years) were included
      in the study. RESULTS: EAT thickness was significantly increased in the SCF group
      compared to the NCF group (7.1 +/- 2.7 vs. 4.7 +/- 1.9 mm, p < 0.001). Body mass
      index (BMI, p < 0.001) and the percentage of isolated SCF (p = 0.002) were
      significantly higher in patients with increased EAT thickness. CRP was not
      related to SCF. When we performed multiple logistic regression analysis, only
      increased EAT thickness was related to the presence of SCF (OR 1.720, 95% CI
      1.175-2.516, p = 0.005) independent of BMI and CRP. CONCLUSIONS: This study
      revealed, for the first time, a significant increase in EAT thickness in patients
      with SCF compared to NCF. We believe that further studies are needed to clarify
      the role of adipose tissue in patients with SCF.

PMID- 22992999
TI  - [Epicardial adipose tissue and coronary artery flow. Does location matter?].

PMID- 22993000
TI  - Impedance cardiography as a tool for haemodynamic monitoring at high altitude: a
      preliminary study.
AB  - BACKGROUND: Altitude illness is a relevant threat to the life and health of
      participants in mountaineering expeditions. AIM: To determine if impedance
      cardiography (ICG) can be used in noninvasive monitoring of haemodynamic
      disturbances at high altitude. METHODS: The study was performed in a group of 13
      participants of two mountaineering expeditions in the Himalayas. The ICG
      examination was performed before the expedition and again at high altitude (4,300
      5,700 m) with concurrent estimates of clinical symptoms of acute mountain
      sickness (AMS) and those suggesting an increased risk of high altitude pulmonary
      oedema (HAPO). RESULTS: High altitude influenced the haemodynamic profile of the
      subjects. Significant changes were observed for: stroke index (baseline vs. high
      altitude: 51.2 +/- 10.3 vs. 35.5 +/- 11.3 mL/m(2); p = 0.0007), cardiac index
      (3.24 +/- 0.49 vs. 2.63 +/- 0.66 L/min/m(2); p = 0.013), Heather index (16.6 +/-
      4.3 vs. 12.8 +/- 4.45 Ohm/s(2); p = 0.006), heart rate (64.1 +/- 11.7 vs. 75.4 +/
      15.4 1/min; p = 0.045) and systemic vascular resistance index (2,051.3 +/- 438.9
      vs. 2,668.4 +/- 856.2 dyn * s * cm(-5) * m(2); p = 0.027). AMS was observed in
      six subjects (mild: n = 5, severe: n = 1). Three of them revealed symptoms
      suggesting an increased risk of HAPO and this subgroup (vs. subgroup without such
      symptoms) was characterised by higher thoracic fluid content index (baseline:
      19.2 +/- 0.9 vs. 17.9 +/- 2.0 1/kOhm x m(2); p = 0.176, at high altitude: 20.8 +/
      1.4 vs. 17.7 +/- 1.6 1/kOhm x m(2); p = 0.018) and lower Heather index
      (baseline: 11.4 +/- 2.0 vs. 18.2 +/- 3.5 Ohm/s(2); p = 0.028, at high altitude:
      9.2 +/- 2.1 vs. 13.9 +/- 4.4 Ohm/s2; p = 0.028). CONCLUSIONS: ICG may be a
      helpful, noninvasive tool in monitoring cardiovascular dysfunction occurring at
      high altitude, especially with breathing disorders.

PMID- 22993001
TI  - CD36 gene is associated with thickness of atheromatous plaque and ankle-brachial
      index in patients with early coronary artery disease.
AB  - BACKGROUND: CD36 is a multifunctional molecule engaged in the removal of oxidised
      LDL from plasma. It is unclear whether mutation of the CD36 gene protects
      against, or increases, the risk of hypercholesterolaemia, atherosclerosis and its
      complications. AIM: To search for associations between the CD36 gene
      polymorphisms and radiological markers of atherosclerosis progress in Caucasian
      patients with coronary artery disease (CAD) diagnosed at a young age. METHODS:
      The study group comprised 70 patients with early CAD. Doppler ultrasound of
      carotid and peripheral arteries was carried out and genomic DNA was isolated from
      each patient. RESULTS: We found two single nucleotide substitutions in introns
      (IVS3-6 T/C - rs3173798 and IVS4-10 G/A - rs3211892) and two synonymous
      polymorphisms in exon 6 (G573A - rs5956 and A591T). The allele frequencies were:
      10.7% for the IVS3-6C, 3.6% for the IVS4-10A, 3.6% for the 573A, and 2.1% for the
      591T. The 573A allele of CD36 rs5956 polymorphism is associated with low
      thickness of atheromatous plaque. The 591T allele is associated with lower ankle
      brachial index. CONCLUSIONS: The 573A allele has a protective effect against
      atherosclerosis development and the 591T allele is a cardiovascular risk factor.
      Assessment of their functional implications requires further research.

PMID- 22993002
TI  - Value of rotational angiography (3D-ATG) with contrast agent administration into
      the right atrium during atrial fibrillation ablation procedures: a preliminary
      report.
AB  - BACKGROUND: Efficacy and safety of radiofrequency (RF) ablation in patients with
      atrial fibrillation (AF) strongly depend on the possibility of three-dimensional
      (3D) visualisation of atria as well as the ostia of pulmonary veins. Current
      angiographic systems allow 3D visualisation of anatomical heart structures using
      rotational angiography. AIM: To evaluate clinical usefulness of rotational
      angiography (3D-ATG) after contrast agent administration into the right atrium
      for the purpose of evaluating left atrial anatomy in patients undergoing RF
      ablation of AF. METHODS: We also compared images obtained using 3D-ATG with
      magnetic resonance imaging (MRI). In 18 consecutive patients undergoing RF
      ablation of AF or left-atrial tachycardia, 3D-ATG was performed uneventfully,
      followed by 3D reconstruction of the left atrium and the aorta. Ablation using
      the CARTO 3 system was successful in 17 patients. Total ablation time was 127 +/-
      28 min, fluoroscopy time 31 +/- 8 min, and radiation dose was 413 +/- 170 mGy.
      Mean fluoroscopy time for 3D-ATG was 1.75 +/- 0.4 min and the mean radiation dose
      was 159 +/- 57 mGy. Appropriate 3D visualisation of the left atrium was possible
      in 17 patients, including 16 patients in whom all 4 pulmonary venous ostia were
      imaged. In 1 patient, all right-sided pulmonary veins were located outside the
      scan area. In 1 case, 3D-ATG did not allow visualisation of the right inferior
      pulmonary vein, and in another case the left-sided veins had a common ostium as
      shown in MRI but not visualised in 3D-ATG. RESULTS: Pulmonary vein diameter
      assessed by 3D-ATG was slightly higher than by MRI (16.6 +/- 3.2 vs. 15.2 +/- 3.6
      mm, p = 0.28), although this was mainly related to a single nonvisualised right
      inferior pulmonary vein. Good agreement (< 2 mm) between the two methods for the
      assessment of pulmonary venous ostia was higher for the right-sided than the left
      sided veins (62.5% vs. 44%, p = 0.03). CONCLUSIONS: We conclude that 3D-ATG after
      contrast agent administration into the right atrium seems to be a safe and
      effective method to visualise pulmonary venous ostia and left atrial anatomy. It
      remains to be established whether it enables evaluation of anatomical anomalies.

PMID- 22993003
TI  - [Heart in 3D and navigation "as in GPS" for ablation in atrial fibrillation].

PMID- 22993004
TI  - [Constrictive pericarditis in echocardiography].
AB  - We present a case of a 53-year-old male with constrictive pericarditis diagnosed
      in echocardiography. The patient had  pericardial resection. The symptomatic
      improvement after pericardiectomy was progressive.

PMID- 22993005
TI  - [Dysfunction of aortic mechanical prosthetic valve - difficulties with
      establishing diagnosis].
AB  - We present 3 cases of the patients with aortic prosthetic valve dysfunction.
      These cases reflect difficulties with establishing  a proper diagnosis which is
      crucial in choosing the way and urgency of treatment.

PMID- 22993006
TI  - [Plasma phosphorus as cardiovascular risk factor in persons with preserved kidney
      function].

PMID- 22993007
TI  - [Postconditioning - can the modified reperfusion improve the results of primary
      coronary angioplasty?].

PMID- 22993008
TI  - [Prevention of stroke in patients with atrial fibrillation and chronic kidney
      disease: difficult choices and clinical decisions].

PMID- 22993009
TI  - [Is erectile dysfunction an independent risk factor of coronary heart disease or
      another clinical manifestation of progressive atherosclerosis?].

PMID- 22993010
TI  - [Higher right precordial leads and Fontaine leads: the better detection of QRS
      fragmentation and epsilon wave in arrhythmogenic right ventricular dysplasia
      cardiomyopathy].
AB  - Epsilon waves (EW) in right precordial leads are reliable diagnostic
      electrocardiographic criteria of arrhythmogenic right  ventricular dysplasia
      cardiomyopathy (ARVD/C). The definition of EW remains difficult because within
      the QRS complex are  inscribed notches or deflections called fragmentation of the
      QRS complex (f-QRS). The f-QRS at the beginning, on the top,  and at the end of
      QRS complex (termed "pre-, top-, and postsilons") was proposed as typical
      extended definition of EW. We  described a 59-year-old female with ARVD with
      severe left ventricular involvement, ejection fraction - 23%. The standard  12
      lead ECG showed QRS fragmentation in 7 leads. It can be a marker of ARVD with
      severe left ventricular disease. EW may  be enhanced visually to 50-75% by
      following placing: the left arm should be placed on the xyphoid process and the
      right arm  lead on the manubrium sternum, with the left leg in the location of V4
      or V5 this is called the Fontaine bipolar precordial lead  (F-ECG). Detection of
      right precordial f-QRS can be improved using higher right precordial leads
      (similar as in Brugada  syndrome). The case we described reminds that EW could be
      enhancing by F-ECG leads and f-QRS by using higher right  precodial leads.

PMID- 22993011
TI  - [Undervalued role of ECG in diagnosis of arrhythmogenic right ventricular
      cardiomyopathy].

PMID- 22993012
TI  - [Primary coronary angioplasty: beyond regular facilities].
AB  - A case of a 59-year-old man in whom primary coronary angioplasty was performed
      using peripheral stent system is presented.

PMID- 22993014
TI  - [Percutaneous left atrial appendage closure with Watchman(r) LAA occluder device
      in a patient with persistent atrial fibrillation].
AB  - We present a case of a 74-year-old male with persistent atrial fibrillation and
      ischaemic stroke despite vitamin-K antagonist  treatment who underwent successful
      left atrial appendage closure with Watchman device.

PMID- 22993016
TI  - [EINSTEIN-PE: rivaroxaban for treatment of symptomatic pulmonary embolism].

PMID- 22993015
TI  - [Do the guidelines always show us the ideal treatment of patients for cardiac
      resynchronisation therapy?].
AB  - We present a case of 80-year-old man with chronic atrial fibrillation and heart
      failure with mildly depressed left ventricular  ejection fraction who
      deteriorated after implantation of pacemaker to right ventricular apex. The
      patient improved when  pacemaker was upgraded to resynchronisation therapy (CRT).
      The question is raised if CRT should have been implanted  primarily.

PMID- 22993017
TI  - [Rivaroxaban for treatment of venous thromboembolism].

PMID- 22993018
TI  - [Cocaine, what else cardiologist should know?].

PMID- 22993019
TI  - [New oral anticoagulants in the prevention of embolic complications in patients
      with atrial fibrillation. Polish Cardiac Society, Polish Neurological Society and
      Working Group on Haemostasis of the Polish Society of Haematologists and
      Transfusiologists consensus statement].

PMID- 22993021
TI  - A new case with 10q23 interstitial deletion encompassing both PTEN and BMPR1A
      narrows the genetic region deleted in juvenile polyposis syndrome.
AB  - We report on a patient with a contiguous interstitial germline deletion of
      chromosome 10q23, encompassing BMPR1A and PTEN, with clinical manifestations of
      juvenile polyposis and minor symptoms of Cowden syndrome (CS) and Bannayan-Riley
      Ruvalcaba syndrome (BRRS). The patient presented dysmorphic features as well as
      developmental delay at the age of 5 months. Multiple polyps along all parts of
      the colon were diagnosed at the age of 3 years, following an episode of a severe
      abdominal pain and intestinal bleeding. The high-resolution comparative genomic
      hybridisation revealed a 3.7-Mb deletion within the 10q23 chromosomal region:
      86,329,859-90,035,024. The genotyping with four polymorphic microsatellite
      markers confirmed a de novo 10q deletion on the allele with a paternal origin,
      encompassing both PTEN and BMPR1A genes. The karyotype analysis additionally
      identified a balanced translocation involving chromosomes 5q and 7q, and an
      inversion at chromosome 2, i.e. 46,XY,t(5;7)(q13.3-q36), inv(2)(p25q34). Although
      many genetic defects were detected, it is most likely that the 10q23 deletion is
      primarily the cause for the serious phenotypic manifestations. The current
      clinical findings and deletion of BMPR1A indicate a diagnosis of severe juvenile
      polyposis, but the existing macrocephaly and PTEN deletion also point to either
      CS or BRRS, which cannot be ruled out at the moment because of their clinical
      manifestation later in life and the de novo character of the deletion. The
      deletion detected in our patient narrows the genetic region deleted in all
      reported cases with juvenile polyposis by 0.04 Mb from the telomeric side,
      mapping it to the region chr10:88.5-90.03Mb (GRCh37/hg19), with an overall length
      of 1.53 Mb.

PMID- 22993020
TI  - Increased risk of osteoporosis-related fractures in patients with irritable bowel
      syndrome.
AB  - We sought to determine whether patients with irritable bowel syndrome (IBS) have
      an increased risk of osteoporosis and related fractures using the Nationwide
      Emergency Department Sample (NEDS). Patients with IBS had increased adjusted odds
      of osteoporosis and osteoporotic fractures compared to the non-IBS control group,
      controlling for known risk factors for osteoporosis. Screening measures to
      identify osteoporosis in this group are advised. INTRODUCTION: Ulcerative
      colitis, Crohn's disease, and celiac disease have well-described augmented risk
      of osteoporosis and related fractures. We sought to determine whether IBS also
      indicates an increased risk of osteoporosis and related fractures. METHODS: The
      2008 NEDS database was used to determine the adjusted odds of osteoporosis and
      related fractures in IBS patients. Only fractures (pathologic wrist (733.12),
      vertebrae (733.13), and femur fractures (733.14), traumatic wrist (813.x),
      vertebrae (805.x-806.x), and hip fractures (820.x-821.x)) with a secondary
      diagnosis of osteoporosis (733.0x) were included in the analysis. A multivariate
      logistic regression analysis was performed, controlling for known risk factors
      for osteoporosis and related fractures. RESULTS: We identified 317,857 ED visits
      in patients with a diagnosis of IBS. Of these, 17,752 carried a diagnosis of
      osteoporosis and 694 IBS patients had a concurrent diagnosis of a pathologic
      fracture of the wrist, hip, or vertebrae. A total of 1,503 IBS patients had a
      concurrent diagnosis of a traumatic fracture of the wrist, hip, or vertebra.
      Overall, patients with IBS had an increased adjusted odds of osteoporosis (odds
      ratio (OR) 4.28, 95% confidence interval (CI) 4.21-4.35) and osteoporotic
      fractures (OR 2.36, CI 2.26-2.47) compared to the non-IBS control group. The
      highest adjusted odds of fracture was seen at the wrist (OR 2.41, CI 2.10-2.77
      compared to controls). CONCLUSIONS: IBS patients are at an increased risk of
      osteoporosis and related fractures. Screening measures to identify osteoporosis
      and prevent fractures are advised.

PMID- 22993022
TI  - Chronic psychological stress and racial disparities in body mass index change
      between Black and White girls aged 10-19.
AB  - BACKGROUND: One of the largest health disparities in the USA is in obesity rates
      between Black and White females. PURPOSE: The objective of this study was to test
      the hypothesis that the stress-obesity link is stronger in Black females than in
      White females aged 10-19. METHODS: Multilevel modeling captured the dynamic of
      acute (1 month) and chronic (10 years) stress and body mass index (BMI; weight in
      kilograms divided by height in meters squared) change in the National Heart,
      Lung, and Blood Institute Growth and Health Study, which consists of 2,379 Black
      and White girls across a span of socioeconomic status. The girls were assessed
      longitudinally from ages 10 to 19. RESULTS: Higher levels of stress during the 10
      years predicted significantly greater increases in BMI over time compared to
      lower levels of stress. This relationship was significantly stronger for Black
      compared to White girls. CONCLUSION: Psychological stress is a modifiable risk
      factor that may moderate early racial disparities in BMI.

PMID- 22993023
TI  - School sport participation under two school sport policies: comparisons by
      race/ethnicity, gender, and socioeconomic status.
AB  - BACKGROUND: School-based extracurricular sport remains an effective strategy to
      increase physical activity. However, school sport is often limited to a small
      number of elite athletes. Few schools provide more inclusive sport programs that
      offer a wider array of activities regardless of ability. PURPOSE: The aim of this
      study was to examine school sport participation in middle schools (ages 11-14)
      with contrasting school sport delivery strategies (intramural vs.
      interscholastic). METHODS: Data were obtained through an online survey
      administered to students at four public middle schools (grades 6-8) in a
      southeastern US city (n = 2,582). RESULTS: More students participated in school
      sports at intramural schools. Boys were more likely to participate in after
      school sports at intramural schools. Low-income and Black children, two groups at
      greater risk of physical inactivity and other negative outcomes, had greater
      participation in intramural programs. CONCLUSIONS: After-school intramural sports
      in middle school is a promising strategy for increasing sport participation.

PMID- 22993024
TI  - Identification of novel splicing variants from RON proto-oncogene pre-mRNA.
AB  - RON is a proto-oncogene that induces cell dissociation, migration and matrix
      invasion. RON?160, a splicing variant of RON, is a natural splicing product in
      colon cancers that is produced through skipping of exons 5 and 6 in alternative
      splicing process. RON?160 promotes cellular transformation in vitro and tumor
      formation in vivo. We present, here, two novel splicing variants of RON in the
      partial splicing events that involve exons 5 and 6. The common facts of these two
      novel splicing variants are that exons 4-7 are included. In addition, intron 4 is
      spliced whereas intron 5 is included in both variants. The difference of these
      two isoforms is the inclusion or skipping of intron 6. In one variant intron 6 is
      included, but intron 6 is skipped in another variant. These two variants should
      be truncated but these proteins have not yet been detected.

PMID- 22993025
TI  - Systematic review of oral cryotherapy for management of oral mucositis caused by
      cancer therapy.
AB  - PURPOSE: This systematic review analyzed the strength of the literature and
      defined clinical practice guidelines for the use of oral cryotherapy for the
      prevention and/or treatment of oral mucositis caused by cancer therapy. METHODS:
      A systematic review on relevant oral cryotherapy studies indexed prior to 31
      December 2010 was conducted by the Mucositis Study Group of the Multinational
      Association of Supportive Care in Cancer/International Society for Oral Oncology
      (MASCC/ISOO) using OVID/MEDLINE, with publications selected for review based on
      defined inclusion and exclusion criteria. Findings from the reviewed studies were
      integrated into guidelines based on the overall level of evidence for each
      intervention. Guidelines were classified into three types: recommendation,
      suggestion, or no guideline possible. RESULTS: Twenty-two clinical studies and
      two meta-analyses were analyzed. Results were compared with the MASCC/ISOO
      guidelines published in 2007. The recommendation for the use of oral cryotherapy
      to prevent oral mucositis in patients receiving bolus fluorouracil (5-FU) was
      maintained, in agreement with the 2007 guidelines. A suggestion for use of oral
      cryotherapy to prevent oral mucositis in patients receiving high-dose melphalan
      as conditioning regimen with or without total body irradiation for HCST was
      revised from the 2007 guidelines. No guideline was possible for any other
      intervention, due to insufficient evidence. CONCLUSIONS: The evidence continues
      to support the use of oral cryotherapy for prevention of oral mucositis in
      patients receiving bolus 5-FU chemotherapy or high-dose melphalan. This
      intervention is consistent with the MASCC/ISOO guidelines published in 2007. The
      literature is limited by the fact that utilization of a double-blind study design
      is not feasible. Future studies that compare efficacy of oral cryotherapy with
      other mucositis agents in patients receiving chemotherapy with relatively short
      plasma half-lives would be useful.

PMID- 22993026
TI  - The pediatric-modified total neuropathy score: a reliable and valid measure of
      chemotherapy-induced peripheral neuropathy in children with non-CNS cancers.
AB  - BACKGROUND: Neurotoxicity is a common side-effect of cancer treatment, but no
      scales have been validated for the pediatric population. The objective of this
      study was to test the reliability and validity of the pediatric modified-Total
      Neuropathy Scale (ped-mTNS) to measure chemotherapy-induced peripheral neuropathy
      in school-aged children. METHODS: Forty-one subjects aged 5-18 years undergoing
      chemotherapy with vincristine or cisplatin and 41 age- and gender-matched
      controls completed study measures. Subjects were tested with the ped-mTNS at a
      specified time during treatment. Standardized measures of balance and hand
      function were completed concurrently. Internal consistency of the ped-mTNS was
      evaluated using Chronbach's alpha. Validity was tested by comparing case and
      control ped-mTNS scores as well as testing the hypothesis that ped-mTNS scores
      would be associated with scores on tests of balance and manual dexterity. Inter
      rater and test-retest reliability were each assessed in a subset of 10 subjects.
      RESULTS: Twenty-three subjects with acute lymphoblastic leukemia, six with
      lymphoma, and 12 with solid tumors completed measures along with 41 age- and
      gender-matched controls. Internal consistency was acceptable with a Chronbach's
      alpha of 0.76. Children undergoing treatment for cancer had significantly worse
      scores on the ped-mTNS compared to controls (subjects, 8.7 +/- 4.2; controls, 1.4
      +/- 0.9; p < 0.001). As hypothesized, scores on the ped-mTNS were associated with
      measures of balance and manual dexterity. Inter-rater and test-retest reliability
      was acceptable (intraclass correlation coefficients >0.9 each). CONCLUSIONS: The
      ped-mTNS is a reliable and valid measure of chemotherapy-induced peripheral
      neuropathy in school-aged children that is associated with relevant functional
      limitations.

PMID- 22993027
TI  - Amelioration of radiation-induced acute inflammation and mucosal atrophy by beta
      hydroxy-beta-methylbutyrate, L-glutamine, and L-arginine: results of an
      experimental study.
AB  - PURPOSE: We aimed to evaluate the effects of beta-hydroxy-beta-methylbutyrate, L
      glutamine, and L-arginine (HMB/Glu/Arg) on radiation-induced acute inflammation
      and mucosal atrophy in the oral mucosa. METHODS: Twenty-eight rats were divided
      into four groups. group (G) 1 was defined as control group, and G2 was the
      radiation therapy (RT) group. G3 and G4 were HMB/Glu/Arg control and 17 Gy RT
      plus HMB/Glu/Arg groups, respectively. A single dose of 17 Gy RT was given to the
      head and neck area, and the active supplement consisting of 5.2 g of HMB, 29.6 g
      arginine, and 29.6 g of glutamine which was equivalent to 60 kg adult dose was
      calculated for each rat and administrated orally. HMB/Glu/Arg started from the
      day of RT and continued until the animals were sacrificed 7 days after the RT.
      The extent of acute inflammation and mucosal atrophy for each rat was quantified
      with image analysis of histological sections of the oral mucosa. RESULTS: There
      were significant differences in terms of epithelial thickness, subepithelial
      edema, inflammation, and congestion between all groups (p values were <0.001,
      0.003, <0.001, and 0.001 for each parameter, respectively). Using HMB/Glu/Arg
      alone led to hypertrophic changes in the epithelial layer. Moreover, when used
      with RT, HMB/Glu/Arg reversed radiation-induced epithelial atrophy (p, 0.006) and
      decreased radiation-induced inflammation at a significant level (p, 0.007).
      CONCLUSION: Concomitant use of HMB/Glu/Arg appears to ameliorate the radiation
      induced acute inflammation and mucosal atrophy which represent the early phase of
      acute oral mucositis; however, this finding should be clarified with further
      clinical studies.

PMID- 22993028
TI  - Systematic monitoring of heathy woodlands in a Mediterranean climate--a practical
      assessment of methods.
AB  - Practical and useful vegetation monitoring methods are needed, and data
      compatibility and validation of remotely sensed data are desirable. Methods have
      not been adequately tested for heathy woodlands. We tested the feasibility of
      detecting species composition shifts in remnant woodland in South Australia,
      comparing historical (1986) plot data with temporal replicates (2010). We
      compared the uniformity of species composition among spatially scattered versus
      spatially clustered plots. At two sites, we compared visual and point-intercept
      estimation of cover and species diversity. Species composition (presence/absence)
      shifted between 1986 and 2010. Species that significantly shifted in frequency
      had low cover. Observations of decreasing species were consistent with
      predictions from temperature response curves (generalised additive models) for
      climate change over the period. However, long-term trends could not be
      distinguished from medium-term dynamics or short-term changes in visibility from
      this dataset. Difficulties were highlighted in assessing compositional change
      using historical baselines established for a different purpose in terms of
      spatial sampling and accuracy of replicate plots, differences in standard plot
      methods and verification of species identifications. Spatially clustered
      replicate plots were more similar in species composition than spatially scattered
      plots, improving change detection potential but decreasing area of inference.
      Visual surveys detected more species than point-intercepts. Visual cover
      estimates differed little from point-intercepts although underestimating cover in
      some instances relative to intercepts. Point-intercepts provide more precise
      cover estimates of dominant species but took longer and were difficult in steep,
      heathy terrain. A decision tree based on costs and benefits is presented
      assessing monitoring options based on data presented. The appropriate method is a
      function of available resources, the need for precise cover estimates versus
      adequate species detection, replication and practical considerations such as
      access and terrain.

PMID- 22993029
TI  - Physico-chemical assessment of paper mill effluent and its heavy metal
      remediation using aquatic macrophytes--a case study at JK Paper mill, Rayagada,
      India.
AB  - The present investigation aims to assess the phytoremediation potential of six
      aquatic macrophytes, viz. Eichhornia crassipes, Hydrilla verticillata, Jussiaea
      repens, Lemna minor, Pistia stratiotes and Trapa natans grown in paper mill
      effluent of JK Paper mill of Rayagada, Orissa, for remediation of heavy metals.
      The experiment was designed in pot culture experiments. Assessment of physico
      chemical parameters of paper mill effluent showed significant decrease in pH,
      conductivity, total dissolved solids, total suspended solids, chlorine, sulphur,
      biological and chemical oxygen demand after growth of macrophytes for 20 days.
      Phytoremediation ability of these aquatic macrophytic species for copper (Cu) and
      mercury (Hg) was indicated by assessing the decrease in the levels of heavy
      metals from effluent water. Maximum reduction (66.5 %) in Hg content of untreated
      paper mill effluent was observed using L. minor followed by T. natans (64.8 %).
      L. minor showed highest reduction (71.4 %) of Cu content from effluent water
      followed by E. crassipes (63.6 %). Phytoextraction potential of L. minor was
      remarkable for Hg and Cu, and bioaccumulation was evident from bioconcentration
      factor values, i.e. 0.59 and 0.70, respectively. The present phytoremediation
      approach was considered more effective than conventional chemical treatment
      method for removing toxic contaminants from paper mill effluent.

PMID- 22993031
TI  - An uncommon cause of asymptomatic primary hyperparathyroidism.

PMID- 22993030
TI  - Mast cells and inflammation-associated colorectal carcinogenesis.
AB  - Close association between chronic inflammation and cancer has been recently
      highlighted. Indeed, inflammatory bowel disease (IBD) has been strongly linked
      with an increased risk of development of colorectal cancer (CRC). Inflammatory
      cell-produced inflammatory mediators, such as proinflammatory cytokines and
      inducible enzymes, contribute to this association. In an inflammatory
      microenvironment, infiltrating macrophages and mast cells mediate production of
      these inflammatory mediators to promote growth of tumors in target tissues. In
      contrast to macrophages, contribution of mast cells to CRC development in
      inflamed colon is not well understood. This study aimed to determine the role of
      mast cells in inflammation-associated colorectal carcinogenesis. CRC was induced
      by administration of the colonic carcinogen, azoxymethane (AOM), and the tumor
      promoter dextran sodium sulfate (DSS) in male mast cell-deficient WBBF(1)-kit
      (W/W-v) (W/W(v)) and mast cell-normal WBB6F(1)-+/+(WT) mice. At week 12, the
      W/W(v) mice had markedly lower inflammation scores in the colon when compared
      with WT mice. The mRNA levels of colonic proinflammatory cytokines and inducible
      enzymes were also decreased in W/W(V) mice at weeks 12 and 20, when compared with
      WT counterparts. Colorectal tumors, including CRC, were identified by
      histopathological analysis performed 20 weeks thereafter. Importantly, there were
      less neoplastic and preneoplastic colonic lesions in the W/W(v) mice compared
      with the WT mice. Thus, for the first time, our study shows that mice lacking
      mast cells are less susceptible to inflammation-associated colorectal
      carcinogenesis. Our findings also suggest that mast cells and their selected
      cytokines could play an important role in inflammation-mediated tumorigenesis
      through regulation of proinflammatory cytokines and inducible inflammatory
      enzymes.

PMID- 22993032
TI  - Serum anti-mullerian hormone levels in healthy females: a nomogram ranging from
      infancy to adulthood.
AB  - CONTEXT: Anti-mullerian hormone (AMH) is an accurate marker of ovarian reserve.
      However, sufficiently large sets of normative data from infancy to the end of
      reproductive life are scarce. OBJECTIVE: This study was an assessment of serum
      AMH levels in healthy females. SUBJECTS: In 804 healthy females ranging from
      infancy until the end of the reproductive period, serum AMH levels were measured
      with an enzyme-linked immunometric assay. All adults had regular menstrual
      cycles. The majority was proven fertile and none of them had used oral
      contraceptive pills prior to study inclusion. RESULTS: In the total cohort, AMH
      was inversely correlated with age (r = -0.24; P < 0.001). The age at which the
      maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr,
      serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter
      AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr
      onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was
      observed. At any given age, considerable interindividual differences in serum AMH
      levels were observed. CONCLUSION: During infancy AMH levels increase, whereas
      during adolescence, a plateau until the age of 25 yr was observed. From the age
      of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH
      is applicable as a marker of ovarian reserve only in women of 25 yr old and
      older. Our nomogram may facilitate counseling women on their reproductive
      potential.

PMID- 22993033
TI  - Health profile of young adults born preterm: negative effects of rapid weight
      gain in early life.
AB  - INTRODUCTION: Early postnatal weight gain is associated with determinants of
      cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2) in adults born
      term. We aimed to investigate the association of weight gain during different
      periods, and weight trajectories in early life after preterm birth, with
      determinants of CVD and DM2 in early adulthood. METHODS: Associations of first
      year growth and tempo of weight gain with determinants of CVD and DM2 in 162
      young adults (18-24 yr) born preterm (gestational age <36 wk) were determined and
      compared with data of young adults born term (n = 217). RESULTS: Gain in weight
      for length in the period from preterm birth up to term age, and in the first 3
      months after term age, was positively associated with body fat percentage and
      waist circumference at 21 yr. Gain in weight for length in the first 3 months
      after term age was also positively associated with total cholesterol and low
      density lipoprotein cholesterol levels in early adulthood. Subjects with the
      highest gain in weight from birth to term age (highest quartile) had
      significantly higher body fat percentage, waist circumference, acute insulin
      response, and disposition index in early adulthood than the subgroups with
      moderate and low gain in weight. Rapid catch-up in weight during the first 3
      months after term age resulted in a higher fat percentage, waist circumference,
      and serum triglycerides level than slower catch-up in weight. CONCLUSION:
      Accelerated neonatal gain in weight relative to length after preterm birth
      (immediately after birth and during the first 3 months after term age) is
      associated with determinants of CVD in early adulthood and should therefore be
      avoided.

PMID- 22993034
TI  - Hazard of breast cancer-specific mortality among women with estrogen receptor
      positive breast cancer after five years from diagnosis: implication for extended
      endocrine therapy.
AB  - PURPOSE: More than half of the patients with estrogen receptor (ER)-positive
      breast cancers will relapse and die from breast cancer at 5-10 yr after diagnosis
      despite 5-yr endocrine therapy. Subpopulations of ER-positive patients at high
      risk of breast cancer-specific mortality (BCSM) at 5-10 yr are undetermined.
      METHODS: Using the Surveillance, Epidemiology, and End-Results program (1990
      2003), we analyzed the relative hazard ratio (HR) and absolute HR of BCSM and the
      cumulative 10-yr breast cancer-specific survival (BCSS) in 111,993 breast cancer
      patients, stratified by ER, age, and lymph node (LN), and adjusted for other
      prognostic factors. RESULTS: At 5-10 yr after diagnosis, ER-positive patients had
      increased risk of BCSM [HR, 0.71; 95% confidence interval (CI), 0.66-0.76; ER
      positive as reference] compared with ER-negative patients. Specifically, younger
      ER-positive patients (<40 yr) had a constant plateau of annual hazard rate, a
      higher hazard of BCSM (HR, 0.43; 95% CI, 0.35-0.52; ER-positive as reference),
      and poor 10-yr BCSS, despite LN status. Among ER-positive patients aged 40-60 yr
      having no obvious plateau of hazard rate, only those with LN-positive disease had
      a significantly increased hazard of BCSM and poor 10-yr BCSS. Elderly ER-positive
      patients aged 60-74 yr had a hazard of BCSM, similar to that of ER-negative
      patients, and those with LN-positive disease had poor 10-yr BCSS. CONCLUSION: Our
      findings help to define the ER-positive subpopulations at higher risk of BCSM at
      5-10 yr after diagnosis and are useful in choosing candidates for clinical trials
      of extended endocrine therapy after 5-yr treatment and in guiding individualized
      treatment.

PMID- 22993035
TI  - Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency.
AB  - CONTEXT: Monocarboxylate transporter 8 (MCT8) is a thyroid hormone-specific cell
      membrane transporter. MCT8 deficiency causes severe psychomotor retardation and
      abnormal thyroid tests. The great majority of affected children cannot walk or
      talk, and all have elevated serum T(3) levels, causing peripheral tissue
      hypermetabolism and inability to maintain weight. Treatment with thyroid hormone
      is ineffective. In Mct8-deficient mice, the thyroid hormone analog,
      diiodothyropropionic acid (DITPA), does not require MCT8 to enter tissues and
      could be an effective alternative to thyroid hormone treatment in humans.
      OBJECTIVE: The objective of the study was to evaluate the effect and efficacy of
      DITPA in children with MCT8 deficiency. METHODS: This was a multicenter report of
      four affected children given DITPA on compassionate grounds for 26-40 months.
      Treatment was initiated at ages 8.5-25 months, beginning with a small dose of 1.8
      mg, increasing to a maximal 30 mg/d (2.1-2.4 mg/kg . d), given in three divided
      doses. RESULTS: DITPA normalized the elevated serum T(3) and TSH when the dose
      reached 1 mg/kg . d and T(4) and rT(3) increased to the lower normal range. The
      following significant changes were also observed: decline in SHBG (in all
      subjects), heart rate (in three of four), and ferritin (in one of four).
      Cholesterol increased in two subjects. There was no weight loss and weight gain
      occurred in two. None of the treated children required a gastric feeding tube or
      developed seizures. No adverse effects were observed. CONCLUSION: DITPA (1-2
      mg/kg . d) almost completely normalizes thyroid tests and reduces the
      hypermetabolism and the tendency for weight loss. The effects of earlier
      commencement and long-term therapy remain to be determined.

PMID- 22993036
TI  - Age-friendly cities of Europe.
AB  - This article summarizes how members of the European Healthy Cities Network have
      applied the 'healthy ageing' approach developed by the World Health Organization
      in their influential report on Active Ageing. Network Cities can be regarded as
      social laboratories testing how municipal strategies and interventions can help
      maintain the health and independence which characterise older people of the third
      age. Evidence of the orientation and scope of city interventions is derived from
      a series of Healthy Ageing Sub-Network symposia but principally from responses by
      59 member cities to a General Evaluation Questionnaire covering Phase IV (2003
      2008) of the Network. Cities elaborated four aspects of healthy ageing (a)
      raising awareness of older people as a resource to society (b) personal and
      community empowerment (c) access to the full range of services, and (d)
      supportive physical and social environments. In conclusion, the key message is
      that by applying healthy ageing strategies to programmes and plans in many
      sectors, city governments can potentially compress the fourth age of 'decrepitude
      and dependence' and expand the third age of 'achievement and independence' with
      more older people contributing to the social and economic life of a city. 

PMID- 22993037
TI  - Swainsonine inhibits growth and potentiates the cytotoxic effect of paclitaxel in
      hepatocellular carcinoma in vitro and in vivo.
AB  - Swainsonine, an extract from Astragalus membranaceus, exhibits broad inhibition
      of growth and pro-apoptotic activity in a number of tumor types. However, the
      underlying mechanism involved remains unclear. To investigate the effects and
      mechanisms of swainsonine on hepatocellular carcinoma (HCC), we performed
      experiments on HepG2, SMCC7721, Huh7 and MHCC97-H human hepatoma and HL-7702
      human hepatocyte cells. We observed that swainsonine significantly inhibited the
      viability of human hepatoma cells in a dose- and time-dependent manner, but did
      not affect human hepatocytes. Due to their highly proliferative and tumorigenic
      nature, we selected MHCC97-H cells as a model system to examine. Swainsonine
      significantly inhibited MHCC97-H cell growth by causing cell cycle arrest at the
      G0/G1 phase and the induction of apoptosis. Blockage of G0/G1 phase was
      accompanied by a decrease in cyclins (D1 and E) and cyclin-dependent kinases
      (Cdk2 and Cdk4) and an increase in the Cdk inhibitors p21 and p27. Furthermore,
      swainsonine enhanced the apoptosis of MHCC97-H cells with the induction of the
      upregulation of Bax and the downregulation of Bcl-2, whereas the expressionof Fas
      and Fas-L remained almost unchanged. These changes were accompanied by the
      enhanced cytoplasmic accumulation of nuclear factor kappaB (NF-kappaB) with a
      concomitant decrease in the nuclear fraction. Importantly, swainsonine also
      potentiated the cytotoxic effects of paclitaxel in vitro and in vivo, in part, by
      restricting the paclitaxel-induced nuclear accumulation of NF-kappaB. Taken
      together, these results suggest that swainsonine may be an important agent
      against HCC via directly inhibiting HCC cell growth and enhancing the
      responsiveness of HCC cells to paclitaxel.

PMID- 22993038
TI  - Expression and role of epithelial cell adhesion molecule in dysplastic nodule and
      hepatocellular carcinoma.
AB  - Epithelial cell adhesion molecule (EpCAM) has been proposed as a marker for
      cancer stem cells in human hepatocellular carcinoma (HCC). However, the function
      and clinical significance of EpCAM in HCC is largely unknown. We examined EpCAM
      expression and localization in 28 dysplastic nodules (DNs) and their
      corresponding cirrhotic nodules, 79 HCC tissue sections and 132 HCC tissue
      microarray cores by immunohistochemistry and determined the relationship to
      clinicopathologic findings. We also examined the role of EpCAM in HCC using
      synthetic small interfering RNA to silence EpCAM gene expression in Huh-7 cells.
      EpCAM expression was very rare in DNs but dominantly appeared in a distinctly
      nodular type of small HCC. Expression of EpCAM was observed in 39% (31/79) of HCC
      tissue sections and in 34.1% (45/132) of tissue microarray sections. EpCAM
      expression in HCC was significantly associated with high tumor grade and serum
      alpha-fetoprotein level. Silencing EpCAM gene expression significantly decreased
      the proliferative activity and invasiveness of HCC cells. EpCAM expression was an
      independent prognostic factor for survival in patients with T1 HCC. The data
      indicate that EpCAM expression occurs at distinct nodular stage of HCC and could
      play an important role in HCC progression.

PMID- 22993039
TI  - MALDI-MS/MS with traveling wave ion mobility for the structural analysis of N
      linked glycans.
AB  - The preference for singly charged ion formation by MALDI makes it a better choice
      than electrospray ionization for profiling mixtures of N-glycans. For structural
      analysis, fragmentation of negative ions often yields more informative spectra
      than fragmentation of positive ones but such ions are more difficult to produce
      from neutral glycans under MALDI conditions. This work investigates conditions
      for the formation of both positive and negative ions by MALDI from N-linked
      glycans released from glycoproteins and their subsequent MS/MS and ion mobility
      behaviour. 2,4,6-Trihydroxyacetophenone (THAP) doped with ammonium nitrate was
      found to give optimal ion yields in negative ion mode. Ammonium chloride or
      phosphate also yielded prominent adducts but anionic carbohydrates such as
      sulfated N-glycans tended to ionize preferentially. Carbohydrates adducted with
      all three adducts (phosphate, chloride, and nitrate) produced good negative ion
      CID spectra but those adducted with iodide and sulfate did not yield fragment
      ions although they gave stronger signals. Fragmentation paralleled that seen
      following electrospray ionization providing superior spectra than could be
      obtained by PSD on MALDI-TOF instruments or with ion traps. In addition, ion
      mobility drift times of the adducted glycans and the ability of this technique to
      separate isomers also mirrored those obtained following ESI sample introduction.
      Ion mobility also allowed profiles to be obtained from samples whose MALDI
      spectra showed no evidence of such ions allowing the technique to be used in
      conditions where sample amounts were limiting. The method was applied to N
      glycans released from the recombinant human immunodeficiency virus glycoprotein,
      gp120.

PMID- 22993040
TI  - A computational model for protein ionization by electrospray based on gas-phase
      basicity.
AB  - Identifying the key factor(s) governing the overall protein charge is crucial for
      the interpretation of electrospray-ionization mass spectrometry data. Current
      hypotheses invoke different principles for folded and unfolded proteins. Here,
      first we investigate the gas-phase structure and energetics of several proteins
      of variable size and different folds. The conformer and protomer space of these
      proteins ions is explored exhaustively by hybrid Monte-Carlo/molecular dynamics
      calculations, allowing for zwitterionic states. From these calculations, the
      apparent gas-phase basicity of desolvated protein ions turns out to be the
      unifying trait dictating protein ionization by electrospray. Next, we develop a
      simple, general, adjustable-parameter-free model for the potential energy
      function of proteins. The model is capable to predict with remarkable accuracy
      the experimental charge of folded proteins and its well-known correlation with
      the square root of protein mass.

PMID- 22993041
TI  - Electron capture dissociation of disulfide, sulfur-selenium, and diselenide bound
      peptides.
AB  - To examine the electron capture dissociation (ECD) behavior of disulfide (S-S),
      sulfur-selenium (S-Se), and diselenide (Se-Se) bonds-containing peptides, a
      series of free cysteine (Cys) and selenocysteine (Sec) containing peptides were
      reacted to form interchain S-S, S-Se, and Se-Se bonds, and then studied using ECD
      with Fourier transform ion cyclotron mass spectrometry (FTICR MS). These results
      demonstrate that the radical has higher tendency to stay at selenium rather than
      sulfur after the cleavage of Se-S bonds by ECD. In addition, -SH (-33), -S (-32),
      and -S + H (-31) small neutral losses were all observed from the cleavage of C-S
      bonds of a disulfide bound peptide. Similar, but minor, fragments were also
      detected in S-Se bound peptides. In contrast, the cleavage of C-Se bonds of the
      Se-Se species mainly forms fragments with neutral loss of -Se + H (-78.90868),
      and the radical tends to stay on the selenium of its corresponding complementary
      pair. Although the electron affinities of S atom (2.07 eV) and Se atom (2.02 eV)
      are very close; they have very different reactivity towards electrons. The
      replacement of sulfur with selenium greatly increases the electron affinities of
      S-Se and Se-Se bonds comparing to S-S bonds (with an increase of electron
      affinity by about 0.20 eV by replacing a sulfur with a selenium) (Int J Quantum
      Chem 110:513-523, 2010), which in turn leads to different ECD fragmentation
      behavior and mechanisms. Our results are in good agreement with previously
      published ab initio calculations on Se-Se compounds by other groups.

PMID- 22993042
TI  - Top-down proteomics and direct surface sampling of neonatal dried blood spots:
      diagnosis of unknown hemoglobin variants.
AB  - We have previously shown that liquid microjunction surface sampling of dried
      blood spots coupled with high resolution top-down mass spectrometry may be used
      for screening of common hemoglobin variants HbS, HbC, and HbD. In order to test
      the robustness of the approach, we have applied the approach to unknown
      hemoglobin variants. Six neonatal dried blood spot samples that had been
      identified as variants, but which could not be diagnosed by current screening
      methods, were analyzed by direct surface sampling top-down mass spectrometry.
      Both collision-induced dissociation and electron transfer dissociation mass
      spectrometry were employed. Four of the samples were identified as beta-chain
      variants: two were heterozygous Hb D-Iran, one was heterozygous Hb Headington,
      and one was heterozygous Hb J-Baltimore. The fifth sample was identified as the
      alpha-chain variant heterozygous Hb Phnom Penh. Analysis of the sixth sample
      suggested that it did not in fact contain a variant. Adoption of the approach in
      the clinic would require speed in both data collection and interpretation. To
      address that issue, we have compared manual data analysis with freely available
      data analysis software (ProsightPTM). The results demonstrate the power of top
      down proteomics for hemoglobin variant analysis in newborn samples.

PMID- 22993043
TI  - Graphite supported preparation (GSP) of alpha-cyano-4-hydroxycinnamic acid (CHCA)
      for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for
      peptides and proteins.
AB  - Graphite as MALDI matrix or in combination with other substances has been
      reported in recent years. Here, we demonstrate that graphite can be used as
      target coating supporting the crystallization of the alpha-cyano-4
      hydroxycinnamic acid matrix. A conventional dried-droplet preparation of matrix
      and analyte solution on a graphite-coated metal target leads to a thin, uniform
      layer of cubic crystals with about 1 MUm edge length. Commercially available
      graphite powder of 1-2 MUm particle size is gently wiped over the target using a
      cotton Q-tip, leading to an ultra-thin, not-visible film. This surface
      modification considerably improves analysis of peptides and proteins for MALDI MS
      using conventional dried-droplet preparation. Compared with untreated targets,
      the signal intensities of standard peptides are up to eight times higher when
      using the graphite supported crystallization. The relative standard deviation in
      peak area of angiotensin II for sample amounts between 1 and 50 fmol is reduced
      to about 15 % compared with 45 % for untreated sample holders. For a
      quantification of 1 fmol of the peptide using an internal standard the
      coefficient of variation is reduced to 3.5 % from 8 %. The new graphite supported
      preparation (GSP) protocol is very simple and does not require any technical nor
      manual skills. All standard solvents for peptides and proteins can be used.

PMID- 22993044
TI  - Dynamically harmonized FT-ICR cell with specially shaped electrodes for
      compensation of inhomogeneity of the magnetic field. Computer simulations of the
      electric field and ion motion dynamics.
AB  - The recently introduced ion trap for FT-ICR mass spectrometers with dynamic
      harmonization showed the highest resolving power ever achieved both for ions with
      moderate masses 500-1000 Da (peptides) as well as ions with very high masses of
      up to 200 kDa (proteins). Such results were obtained for superconducting magnets
      of very high homogeneity of the magnetic field. For magnets with lower
      homogeneity, the time of transient duration would be smaller. In superconducting
      magnets used in FT-ICR mass spectrometry the inhomogeneity of the magnetic field
      in its axial direction prevails over the inhomogeneity in other directions and
      should be considered as the main factor influencing the synchronic motion of the
      ion cloud. The inhomogeneity leads to a dependence of the cyclotron frequency
      from the amplitude of axial oscillation in the potential well of the ion trap. As
      a consequence, ions in an ion cloud become dephased, which leads to signal
      attenuation and decrease in the resolving power. Ion cyclotron frequency is also
      affected by the radial component of the electric field. Hence, by appropriately
      adjusting the electric field one can compensate the inhomogeneity of the magnetic
      field and align the cyclotron frequency in the whole range of amplitudes of z
      oscillations. A method of magnetic field inhomogeneity compensation in a
      dynamically harmonized FT-ICR cell is presented, based on adding of extra
      electrodes into the cell shaped in such a way that the averaged electric field
      created by these electrodes produces a counter force to the forces caused by the
      inhomogeneous magnetic field.

PMID- 22993045
TI  - Relative quantitation of neuropeptides over a thousand-fold concentration range.
AB  - Neuropeptides are essential cell-to-cell signaling molecules that influence
      diverse regulatory and behavioral functions within biological systems. Differing
      in their amino acid sequences and post-translational modifications, hundreds of
      neuropeptides are produced via a series of enzymatic processing steps, and their
      levels vary with location, time, and physiological condition. Due to their wide
      range of endogenous concentrations and inherent chemical complexity, using mass
      spectrometry (MS) to accurately quantify changes in peptide levels can be
      challenging. Here we evaluate three different MS systems for their ability to
      accurately measure neuropeptide levels: capillary liquid chromatography
      electrospray ionization-ion trap (CapLC-ESI-IT) MS, ultraperformance liquid
      chromatography-electrospray ionization-quadrupole-time-of-flight (UPLC-LC-ESI-Q
      TOF) MS, and matrix-assisted laser desorption/ionization-time-of-flight (MALDI
      TOF) MS. Specifically, eight sample mixtures composed of five neuropeptide
      standards, with four technical replicates of each, were labeled with H(4)/D(4)
      succinic anhydride, followed by relative peptide quantitation using the three MS
      platforms. For these samples, the CapLC-ESI-IT MS platform offered the most
      robust ability to accurately quantify peptides over a concentration range of 1200
      fold, although it required larger sample sizes than the other two platforms. Both
      the UPLC-ESI-Q-TOF MS and the MALDI-TOF MS systems had lower limits of
      quantification, with the MALDI-TOF having the lowest. By implementing several
      data acquisition schemes and optimizing the data analysis approaches, we were
      able to accurately quantify peptides over a three orders of magnitude
      concentration range using either the UPLC or MALDI-TOF platforms. Overall these
      results increase our understanding of both the capabilities and limits of using
      MS-based approaches to measure peptides.

PMID- 22993046
TI  - Electrospray ionization-induced protein unfolding.
AB  - Electrospray ionization mass spectrometry (ESI-MS) measurements were performed
      under a variety of solution conditions on a highly acidic sub-fragment (B3C) of
      the C-terminal carbohydrate-binding repeat region of Clostridium difficile toxin
      B, and two mutants (B4A and B4B) containing fewer acidic residues. ESI-MS
      measurements performed in negative ion mode on aqueous ammonium acetate solutions
      of B3C at low ionic strength (I < 80 mM) revealed evidence, based on the measured
      charge state distribution, of protein unfolding. In contrast, no evidence of
      unfolding was detected from ESI-MS measurements made in positive ion mode at low
      I or in either mode at higher I. The results of proton nuclear magnetic resonance
      and circular dichroism spectroscopy measurements and gel filtration
      chromatography performed on solutions of B3C under low and high I conditions
      suggest that the protein exists predominantly in a folded state in neutral
      aqueous solutions with I > 10 mM. The results of ESI-MS measurements performed on
      B3C in a series of solutions with high I at pH 5 to 9 rule out the possibility
      that the structural changes are related to ESI-induced changes in pH. It is
      proposed that unfolding of B3C, observed in negative mode for solutions with low
      I, occurs during the ESI process and arises due to Coulombic repulsion between
      the negatively charged residues and liquid/droplet surface charge. ESI-MS
      measurements performed in negative ion mode on B4A and B4B also reveal a shift to
      higher charge states at low I but the magnitude of the changes are smaller than
      observed for B3C.

PMID- 22993047
TI  - Minimizing carry-over in an online pepsin digestion system used for the H/D
      exchange mass spectrometric analysis of an IgG1 monoclonal antibody.
AB  - Chromatographic carry-over can severely distort measurements of amide H/D
      exchange in proteins analyzed by LC/MS. In this work, we explored the origin of
      carry-over in the online digestion of an IgG1 monoclonal antibody using an
      immobilized pepsin column under quenched H/D exchange conditions (pH 2.5, 0 
      degrees C). From a consensus list of 169 different peptides consistently detected
      during digestion of this large, ~150 kDa protein, approximately 30% of the peptic
      peptides exhibited carry-over. The majority of carry-over originates from the
      online digestion. Carry-over can be substantially decreased by washing the online
      digestion flow-path and pepsin column with two wash cocktails: [acetonitrile
      (5%)/isopropanol (5%)/acetic acid (20%) in water] and [2 M guanidine
      hydrochloride in 100 mM phosphate buffer pH 2.5]. Extended use of this two-step
      washing procedure does not adversely affect the specificity or activity of the
      immobilized pepsin column. The results suggest that although the mechanism of
      carry-over appears to be chemical in nature, and not hydrodynamic, carry-over
      cannot be attributed to a single factor such as mass, abundance, pI, or
      hydrophobicity of the peptides.

PMID- 22993048
TI  - Mass spectrometry parameters optimization for the 46 multiclass pesticides
      determination in strawberries with gas chromatography ion-trap tandem mass
      spectrometry.
AB  - Multiclass analysis method was optimized in order to analyze pesticides traces by
      gas chromatography with ion-trap and tandem mass spectrometry (GC-MS/MS). The
      influence of some analytical parameters on pesticide signal response was
      explored. Five ion trap mass spectrometry (IT-MS) operating parameters, including
      isolation time (IT), excitation voltage (EV), excitation time (ET), maximum
      excitation energy or "q" value (q), and isolation mass window (IMW) were
      numerically tested in order to maximize the instrument analytical signal
      response. For this, multiple linear regression was used in data analysis to
      evaluate the influence of the five parameters on the analytical response in the
      ion trap mass spectrometer and to predict its response. The assessment of the
      five parameters based on the regression equations substantially increased the
      sensitivity of IT-MS/MS in the MS/MS mode. The results obtained show that for
      most of the pesticides, these parameters have a strong influence on both signal
      response and detection limit. Using the optimized method, a multiclass pesticide
      analysis was performed for 46 pesticides in a strawberry matrix. Levels higher
      than the limit established for strawberries by the European Union were found in
      some samples.

PMID- 22993050
TI  - Modification of the behavioral effects of morphine in rats by serotonin 5-HT1A
      and 5-HT2A receptor agonists: antinociception, drug discrimination, and locomotor
      activity.
AB  - RATIONALE: Indirect-acting serotonin (5-HT) receptor agonists can enhance the
      antinociceptive effects of morphine; however, the specific 5-HT receptor
      subtype(s) mediating this enhancement is not established. OBJECTIVE: This study
      examined interactions between morphine and both 5-HT(1A) and 5-HT(2A) receptor
      agonists in rats using measures of antinociception (radiant heat tail flick and
      warm water tail withdrawal), drug discrimination (3.2 mg/kg morphine versus
      saline), and locomotion. METHODS: Male Sprague-Dawley rats (n = 7-8 per group)
      were used to examine the effects of morphine alone and in combination with DOM (5
      HT(2A) agonist) and 8-OH-DPAT (5-HT(1A) agonist). RESULTS: DOM did not modify
      antinociceptive or discriminative stimulus effects while modestly attenuating
      locomotor-stimulating effects of morphine; the effect of DOM (0.32 mg/kg) on
      morphine-induced locomotion was prevented by the 5-HT(2A) receptor-selective
      antagonist MDL 100907. In contrast, 8-OH-DPAT (0.032-0.32 mg/kg) fully attenuated
      the antinociceptive effects (both procedures), did not modify the discriminative
      stimulus effects, and enhanced (0.32 mg/kg) the locomotor-stimulating effects of
      morphine. These effects of 8-OH-DPAT were prevented by the 5-HT(1A) receptor
      selective antagonist WAY100635. CONCLUSION: Agonists acting at 5-HT(1A) or 5
      HT(2A) receptors do not modify all effects of mu opioid receptor agonists in a
      similar manner. Moreover, interactions between 5-HT and opioid receptor agonists
      vary significantly between rats and nonhuman primates, underscoring the value of
      comparing drug interactions across a broad range of conditions and in multiple
      species.

PMID- 22993049
TI  - Modulation of nociception by social factors in rodents: contribution of the
      opioid system.
AB  - RATIONALE: The opioid system is involved in the regulation of several behavioral
      and physiological responses, controlling pain, reward, and addictive behaviors.
      Opioid administration, depending on drugs and doses, usually affects sociability
      reducing interactions between conspecifics, whereas some affiliative behaviors
      such as sexual activity, social grooming, and play behavior increase the
      endogenous opioid activity. OBJECTIVES: The possible interaction between
      endogenous opioids released during socio/sexual behavior and their analgesic
      effect on pain response is reviewed in the rodent literature. RESULTS: Direct
      evidence for socially mediated opioid changes resulting in increase in
      nociceptive threshold derives from studies exploring the effects of defeat
      experiences, social isolation, maternal, sexual behavior, and social reunion
      among kin or familiar animals in laboratory rodents. Indirect evidence for
      endogenous activation of the opioid system, possibly affecting pain sensitivity,
      derives from studies investigating the relevance of natural social reward using
      the conditioned place preference protocols or analyzing ultrasonic vocalizations
      associated to positive affective contexts. Finally, genetic and epigenetic
      factors that affect the opioid system during development are reported to be
      involved in modulating the response to social stimuli as well as nociception.
      CONCLUSIONS: All studies highlight the relevance of affiliative contact behavior
      between conspecifics that is responsible for the activation of the endogenous mu
      opioid system, inducing nociceptive threshold increase.

PMID- 22993051
TI  - The acute effects of yogic breathing exercises on craving and withdrawal symptoms
      in abstaining smokers.
AB  - RATIONALE: Breathing exercises have been proposed as a way of combating cigarette
      cravings, potentially presenting a low-cost, easily scalable smoking cessation
      aid. OBJECTIVE: The aim of this study is to evaluate the acute impact of
      breathing exercises based on yogic pranayama on cravings in abstaining smokers.
      METHODS: Participants visited the laboratory on two occasions 24 h apart and were
      asked to abstain from smoking 12 h prior to the first visit until the end of the
      second visit. Smokers (N = 96) were randomly allocated to a yogic breathing
      exercise (YBG) or video control (VCG) group. The former was instructed on
      breathing exercises, practised these for 10 min and asked to use these when
      experiencing cravings until the next visit. The latter was shown a breathing
      exercise video for 10 min and asked to concentrate on their breathing. Strength
      of urges to smoke, other craving measures and mood and physical symptoms
      associated with cigarette withdrawal were assessed at the beginning and end of
      the first visit, and again at the second visit. RESULTS: At immediate follow-up,
      in the laboratory, all craving measures were reduced in YBG compared with VCG
      (strength of urges: F(1, 96) = 16.1, p < 0.001; cigarette craving: F(1, 96) =
      11.3, p = 0.001; desire to smoke: F(1, 96) = 6.6, p = 0.012). There was no effect
      on mood or physical symptoms. Adherence to the breathing exercise regimen in the
      following 24 h was low, and at 24 h follow-up, there was no evidence of reduced
      cravings in YBG compared with VCG. CONCLUSIONS: Simple yogic-style breathing
      exercises can reduce cigarette craving acutely in the laboratory. Further
      research is needed to determine how far this translates into field settings.

PMID- 22993052
TI  - Examination of behavioral strategies regulating cocaine intake in rats.
AB  - RATIONALE: It has long been observed that rats self-administer psychostimulants
      in a highly regular pattern. The inverse relationship between dose and rate of
      drug intake has been interpreted as a titration phenomenon wherein brain-cocaine
      levels are maintained within a range. Most studies examining this phenomenon have
      used fixed, unit doses in which case the only titration strategy available to the
      animal is to adjust inter-infusion intervals. OBJECTIVES: In this study, we
      examined whether selection of dose size could also be a factor in regulation of
      intake. We used a schedule of reinforcement, under which the dose can vary
      through a wide range and is determined by the behavior of the animal. METHODS:
      Rats self-administered cocaine using a behaviorally dependent dosing schedule of
      reinforcement, under which the size of each dose was determined by the length of
      time the lever was held down. The concentration of cocaine was changed across
      sessions. RESULTS: Total pump-time self-administered decreased by 56 % following
      each doubling of the concentration, which led to an average 11 % increase in
      total intake. Similarly, estimated brain levels of cocaine increased by 12 % for
      each doubling of concentration. These adjustments were the result of manipulation
      of both the size and spacing of infusions. CONCLUSIONS: In agreement with
      previous studies, the regular pattern of intake appears to be the result of a
      titration mechanism in which animals maintain brain levels of cocaine above some
      threshold. Compensatory regulation appeared to involve both the selection of dose
      size and inter-infusion intervals.

PMID- 22993054
TI  - Clinical application of photopic negative response of the flash electroretinogram
      in primary open-angle Glaucoma.
AB  - PURPOSE: To evaluate the diagnostic performance of the photopic negative response
      (PhNR) for the detection of primary open-angle glaucoma (POAG). METHODS: Fifty
      two normal subjects (52 eyes) and 173 POAG patients (173 eyes) were studied. The
      PhNR was elicited using a white stimuli on a white background. The mean deviation
      (MD) and pattern standard deviation (PSD) of the visual field were measured using
      standard automated perimetry (SAP). Spectral domain optical coherence tomography
      (SD-OCT) was used to measure the mean thickness of the retinal nerve fiber layer
      (RNFL). RESULTS: In the glaucoma group, as compared to the normal group, the
      amplitudes of a-waves, b-waves and PhNR were significantly smaller (P<0.001), and
      the PhNR implicit time was significantly longer (P=0.004). The MD, PSD and mean
      thickness of the RNFL were significantly correlated with the amplitude of the
      PhNR (P<0.001). The area under the receiver operating characteristic curve (AUCs)
      for the amplitudes of a-waves, b-waves and PhNR were 0.853, 0.830 and 0.918,
      respectively. When the specificity was >= 95%, the sensitivities were 60.4%,
      54.2% and 85.4% respectively. CONCLUSION: The PhNR amplitude was reduced even
      when the loss in visual field sensitivity was mild, which suggests that PhNR
      might be a useful indicator of early glaucoma disease.

PMID- 22993053
TI  - Combination of apoptin with photodynamic therapy induces nasopharyngeal carcinoma
      cell death in vitro and in vivo.
AB  - Photodynamic therapy has been developed as a viable treatment for cancer, while
      apoptin is an apoptosis-inducing protein. This study was undertaken to evaluate
      the feasibility and efficacy of apoptin with photodynamic therapy (PDT) in the
      treatment of nasopharyngeal carcinoma (NPC). RT-PCR and western blotting were
      used to detect the expression of apoptin in CNE-2 NPC cells. MTT and flow
      cytometry analysis were used to detect cell proliferation and cell apoptosis,
      respectively. Transmission electron microscopy was used to observe cell
      structures. Hematoxylin and eosin staining was used to observe the xenograft
      morphology. The expression of apoptin was analyzed by RT-PCR and western blotting
      in CNE-2 cells stably transfected with PVP3 plasmid. Apoptin restrained cell
      proliferation and enhanced cell apoptosis compared to controls. Furthermore, we
      demonstrated that apoptin augmented the effect of PDT with stronger cell
      proliferation restraint and cell apoptosis and induced severe ultrastructural
      morphology changes compared to controls. Additionally, we found that the
      combination of apoptin and PDT produced the strongest inhibition of xenograft
      growth and tumor necrosis in in vivo experiments. Collectively, we show that
      apoptin in combination with PDT has a better therapeutic effect in NPC than PDT
      therapy or apoptin gene therapy alone.

PMID- 22993055
TI  - Coreoplasty and Artisan intraocular lens implantation for mydriasis and aphakic
      correction in post-traumatic vitrectomized eyes.
AB  - PURPOSE: To evaluate the efficacy and safety of using coreoplasty, and an iris
      supported Artisan intraocular lens (IOL), for mydriasis and aphakic correction in
      post-traumatic vitrectomized eyes. METHODS: A total of 17 aphakic patients were
      admitted between April 2009 and April 2010 to the ophthalmologic department of
      Xiamen Eye Center. All eyes had previously received lens removal and vitrectomy.
      After the retina stabilized and corrected visual acuity improved, the iris was
      sutured. The Artisan IOL was fixated onto the iris surface. Patients were
      followed-up at one day, one week, one month and three months postoperatively. The
      following outcomes were assessed: symptoms of photophobia and glare, uncorrected
      visual acuity (UCVA), best-corrected visual acuity (BCVA), intraocular pressure
      (IOP), endothelial cell density (ECD). The diameter of pupil and the anterior
      chamber depth (ACD) were measured by the anterior segment optical coherence
      tomography (OCT). RESULTS: Artisan IOLs were successfully implanted in all
      aphakic eyes. Postoperatively, improvement was observed in photophobia and glare
      symptoms. UCVA was enhanced in all patients (six eyes had better UCVA
      postoperatively than BCVA preoperatively). However, there were no significant
      changes in IOP. Mean loss of ECD was 336.06/mm2. Mean postoperative pupil
      diameter was 3.67+/-0.41mm, compared with 5.67+/-0.57mm preoperatively (P<0.05).
      Mean ACD was reduced by 0.88mm (3.38+/-0.33mm preoperatively vs 2.50+/-0.35mm
      postoperatively, P<0.05). CONCLUSION: Surgery that combined coreoplasty and
      Artisan IOL implantation was a safe and effective treatment for correcting
      aphakia and mydriasis in post-traumatic vitrectomized eyes.

PMID- 22993056
TI  - Correlation between lens thickness and central anterior chamber depth.
AB  - PURPOSE: To investigate gender differences in lens thickness (LT) and central
      anterior chamber depth (ACD) in normal subjects, and to assess age associated
      changes in these measures. METHODS: The anterior chamber depth (ACD), and lens
      thickness (LT), of 150 normal subjects (150 eyes) was measured by anterior
      segment optical coherence tomography (AS- OCT). Gender differences were assessed
      by independent t-test, and correlation analysis was used to examine the effect of
      age. RESULTS: The mean values of ACD and LT were 0.69+/-0.32 mm and 4.85+/-0.43
      mm, respectively. Women had a significantly lower Mean ACD as compared to men
      (2.56+/-0.33mm vs 2.85+/-0.29 mm; P<0.05). No statistically significant
      difference was found in LT between male and female subjects (P>0.05). Correlation
      analysis findings suggest that LT increases with age (r =0.83, P<0.05), and that
      ACD decreases with age (r=- 0.57, P<0.05). After controlling for LT, no
      significant correlation was observed between age and ACD (P>0.05). CONCLUSION:
      The ACD of female subjects was, on average, shallower than that of their male
      counterparts. Aging was associated with increasing LT, and the observed narrowing
      of ACD with age, might be partially mediated by the increasing LT.

PMID- 22993057
TI  - Histological and ultrastructural features for proliferation inhibition by
      delivery of exogenous p27Kip1 to rabbit models after glaucoma filtration surgery.
AB  - PURPOSE: To investigate postoperative inhibition of cell proliferation in animals
      treated with exogenous p27Kip1 during an experimental glaucoma filtration surgery
      (GFS) by histological and ultrastructural examinations. METHODS: The primer was
      designed according to p27Kip1 gene sequence of GenBank. The p27Kip1-expressing
      adenovirus-mediated Ad-p27 was constructed according to standard techniques. Gene
      therapy was performed by subconjunctival delivery of Ad-p27, mitomycin C (MMC)
      and PBS served as controls. Histological and ultastructural changes at surgical
      sites were observed for 28 days postoperatively. RESULTS: Histologically, evident
      cellular proliferation induced by Ad-p27 was observed on day 7, with appreciable
      filtering cavity. However, thin conjunctival layers were noted, and the number of
      fibroblasts decreased in the Tenon's capsule on day 14. On day 28, the filtering
      cavity partially disappeared. The histological features of the animals with MMC
      delivery were similar to those treated by Ad-p27. In contrast, in the PBS
      treatment group, thick conjunctival layers were observed, and the number of
      goblet cells and fibroblasts, increased markedly. The filtering cavity
      disappeared at postoperative day 21. Twenty eight day postoperatively,
      ultrastructural findings showed that most conjunctival epithelial cells in the Ad
      p27 treatment group were under static state, and that organelles were inactive.
      The number of goblet cells, and the secretion of mucin, were decreased. The
      amount of fibroblasts also decreased with partial apoptotic cells. The
      ultrastructural features presented by rabbits with the MMC delivery resembled
      those treated with Ad-p27. In the PBS treatment group, the number of conjunctival
      epithelial cells increased; the amount of goblet cells increased as the secretion
      of mucin was strengthened, and a substantial amount of fibroblasts were observed
      with active and productive organelles. CONCLUSION: Ad-p27 inhibits the
      proliferation of Tenon's capsule fibroblasts at surgical sites, and suppresses
      the formation of scars, thereby promoting surgical efficacy.

PMID- 22993058
TI  - Application value of topical aneasthesia in children strabismus surgery.
AB  - PURPOSE: Comparison of topical vs general aneasthesia for strabismus surgery.
      METHODS: Preoperative patients (aged 6~12 years) were divided into two study
      groups: the topical aneasthesia group (n=22), and the general aneasthesia group
      (n=21). The study groups were compared on the following measures: analgesic
      effect, surgical correction effect, eye-heart reflex, preoperative preparation
      time and operation time, using t-tests or X2 tests where appropriate. RESULTS:
      Compared with the general aneasthesia group, the topical aneasthesia group gained
      better surgical correction results (P<0.05), had a lower rate of eye-heart reflex
      (P<0.05), and had a shorter preoperative preparation time (P<0.001). No
      significant difference was observed between the groups in terms of the analgesic
      effect or operation time (P>0.05). CONCLUSION: Topical aneasthesia represents a
      safe and effective alternative to general aneasthesia for strabismus surgery in
      children.

PMID- 22993059
TI  - Lipofuscin- and melanin-related fundus autofluorescence in patients with
      submacular idiopathic choroidal neovascularization.
AB  - PURPOSE: To compare melanin-related near-infrared fundus autofluorescence (NIA;
      excitation 787 nm, emission> 800 nm) with lipofuscin-related fundus
      autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with
      idiopathic choroidal neovascularization (ICNV). METHODS: FAF, NIA, fundus
      fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were
      obtained using a confocal scanning laser Ophthalmoscope HRA2 (Heidelberg Retina
      Angiograph 2) in 18 eyes of 18 patients with ICNV. RESULTS: Eighteen eyes had
      classic CNV, and autofluorescence imaging showed hypoautofluorescence at the site
      of CNV. A well-defined hyperautofluorescent ring was detected surrounding the CNV
      in all 18 eyes with NIA imaging. In our sample, the FAF patterns around the CNV
      were classified as normal (n=1, 5.56%), well-defined hyperautofluorescent ring
      (n=7, 38.89%), or ill-defined hyperautofluorescent ring (n=10, 55.56%).
      CONCLUSION: The patterns of FAF and NIA indicated different involvement of
      lipofuscin and melanin in the pathophysiological process of ICNV. Compared to FAF
      imaging, NIA imaging appears to be a superior noninvasive method for in vivo
      visualization of retinal pigment epithelium (RPE) abnormalities in ICNV patients.

PMID- 22993060
TI  - Efficacy of progressive addition lenses in the treatment of ametropia after the
      single eye's IOL implantation.
AB  - PURPOSE: To investigate the efficacy of progressive addition lenses on the
      treatment of ametropia and loss of accomodation after the single eye's IOL
      implantation. METHODS: Eighty four patients undergoing IOL implantation in single
      eyes were prescribed with progressive addition lenses for ametropia correction
      and regularly followed up to observe subsequent correction effect. RESULTS: Among
      these 84 patients, 72 could comfortably adapt to the use of progressive addition
      lenses to improve visual acuity and accomondation, while the remaining 12
      patients failed to accomodate the usage of progressive addition lenses.
      CONCLUSION: Wearing progressive addition lenses acts as a relatively feasible
      approach to improve visual acuity and alleviate disorders of accomodation for
      patients who underwent IOL implantation in single eyes. The patients should be
      prescribed with progressive lenses under professional instructions and guidance.

PMID- 22993061
TI  - Clinical analysis of cataract surgery complicated by endophthalmitis.
AB  - PURPOSE: To assess the efficacy of vitrectomy combined with intravitreal
      injection in the treatment of endophthalmitis after phacoemulsification and IOL
      implantation. METHODS: Five patients (5 eyes), who had undergone conventional
      phacoemulsification combined with IOL implantation at another treatment facility,
      presented with endophthalmitis. The subjects ranged in age from 41 to 79 years
      (65.8 +/- 0.5 years on average), and three were male. All five cases received
      bacterial culture susceptibility testing. On the basis of the treatment of
      primary disease, 3 cases had anterior chamber irrigation, and posterior
      vitrectomy followed by intravitreal injection of 1 mg vancomycin plus 2.25 mg
      ceftazidime. RESULTS: Four out of the five cases of endophthalmitis had a
      positive bacterial culture testing results (two cases of staphylococcus
      epidermidis, one case of enterococcus faecalis and one case of head-like
      staphylococcus), and the remaining case had no bacterial growth. Four cases
      showed restored visual acuity, clear vitreous cavity, and no retinal detachment
      or other complications. CONCLUSION: Management of patients presenting with
      endophthalmitis subsequent to cataract surgery should include: prompt bacterial
      culture and drug sensitivity tests, and where appropriate, vitrectomy combined
      with intravitreal injection of vancomycin.

PMID- 22993062
TI  - Different dosages of intravitreal triamcinolone acetonide injections for macular
      edema secondary to central retinal vein occlusion.
AB  - PURPOSE: To study the effect of intravitreal injections of triamcinolone
      acetonide (TA) for the treatment of macular edema secondary to central retinal
      vein occlusion (CRVO) in a sample of Chinese patients from Shaanxi province.
      METHODS: The 50 eyes from 50 patients were separated into three TA treatment
      groups: 17 patients were given 4mg /0.1ml, 19 patients were given 8mg /0.2ml, and
      14 patients were given 16mg /0.4ml. Patients were followed up for 12 months.
      Foveal thickness, intraocular pressure (IOP), and best-corrected visual acuity
      (BCVA) were measured. RESULTS: Macular edema responded well both anatomically and
      functionally to the TA injections. After the initial intravitreal injection,
      macular edema recurred at 2-4 months in the low-dose group (4 mg), at 3-5 months
      in the medium-dose group (8 mg), and at 6-9 months in the high-dose group (16
      mg). No significant difference in BCVA or in foveal thickness were observed
      between the first intravitreal injection and the re-injection. There was no
      increase in IOP after re-injection of 16mg TA, if the patient did not have an
      elevated IOP after the initial intravitreal injection of 4/8 mg TA. CONCLUSION: A
      low dosage of TA(4 mg) administered via intravitreal injection might be useful as
      an initial treatment for macular edema secondary to CRVO. A higher dosage of TA
      (16mg) can be used if there is no IOP elevation with the initial TA injection.

PMID- 22993063
TI  - Late postoperative opacification of the hydrophobic acrylic intraocular lens in
      both eyes.
AB  - PURPOSE: To report on the clinical findings of a case of late opacification of
      the hydrophobic acrylic intraocular lens (IOLs) in both eyes after cataract
      surgery. METHODS: A 79-year-old man with a history of decreased visual acuity and
      complaints of glare and blurred vision in both eyes over the past 3 years. He had
      received an uneventful phacoemulsification combined with posterior chamber IOL
      implantation for senile cataract in both eyes 13 years ago, and had undergone
      neodymium:YAG(Nd:YAG) laser posterior capsulotomy on both eyes 6 years ago, for
      posterior capsular opacification (PCO). The optical portion of the IOLs showed
      uniform gray haze. Binocular posterior capsular laser holes were clearly noted.
      RESULTS: IOL exchange was performed by the same surgeon on both eyes, three days
      apart. Postoperatively, the patient's visual acuity was elevated to 6/12 (OD) and
      6/9 (OS) at 6 months, and intraocular pressure (IOP) reached 16.8 mmHg (OD) and
      18.4 mmHg (OS). Neither glare or blurred vision were observed in either eye.
      CONCLUSION: IOL exchange can be used to effectively manage clinically significant
      optic opacification.

PMID- 22993064
TI  - The small heat shock proteins alphaB-crystallin and Hsp27 suppress SOD1
      aggregation in vitro.
AB  - Amyotrophic lateral sclerosis is a devastating neurodegenerative disease. The
      mechanism that underlies amyotrophic lateral sclerosis (ALS) pathology remains
      unclear, but protein inclusions are associated with all forms of the disease.
      Apart from pathogenic proteins, such as TDP-43 and SOD1, other proteins are
      associated with ALS inclusions including small heat shock proteins. However,
      whether small heat shock proteins have a direct effect on SOD1 aggregation
      remains unknown. In this study, we have examined the ability of small heat shock
      proteins alphaB-crystallin and Hsp27 to inhibit the aggregation of SOD1 in vitro.
      We show that these chaperone proteins suppress the increase in thioflavin T
      fluorescence associated with SOD1 aggregation, primarily through inhibiting
      aggregate growth, not the lag phase in which nuclei are formed. alphaB-crystallin
      forms high molecular mass complexes with SOD1 and binds directly to SOD1
      aggregates. Our data are consistent with an overload of proteostasis systems
      being associated with pathology in ALS.

PMID- 22993065
TI  - Upregulation of nestin in proximal tubules may participate in cell migration
      during renal repair.
AB  - The characteristics of renal tubular progenitor/precursor cells and the role of
      renal tubule regeneration in the repair of remnant kidneys (RKs) after
      nephrectomy are not well known. In the present study of a murine model of
      subtotal nephrectomy, we used immunofluorescence (IF), immunoblot analysis, and
      in situ hybridization methods to demonstrate that nestin expression was
      transiently upregulated in tubule cells near the incision edges of RKs. The
      nestin-positive tubules were immature proximal tubules that colabeled with lotus
      tetragonolobus agglutinin but not with markers of mature tubules (aquaporin-1,
      Tamm-Horsfall protein, and aquaporin-2). In addition, many of the nestin
      expressing tubule cells were actively proliferative cells, as indicated by
      colabeling with bromodeoxyuridine. Double-label IF and immunoblot analysis also
      showed that the upregulation of tubular nestin was associated with enhanced
      transforming growth factor-beta1 (TGF-beta1) expression in the incision edge of
      RKs but not alpha-smooth muscle actin, which is a marker of fibrosis. In cultured
      human kidney proximal tubule cells (HKC), immunoblot analysis indicated that TGF
      beta1 induced nestin expression and loss of E-cadherin expression, suggesting an
      association of nestin expression and cellular dedifferentiation. Knockdown of
      nestin expression by a short hairpin RNA-containing plasmid led to decreased
      migration of HKC cells that were induced by TGF-beta1. Taken together, our
      results suggest that the tubule repair that occurs during the recovery process
      following nephrectomy may involve TGF-beta1-induced nestin expression in immature
      renal proximal tubule cells and the promotion of renal cell migration.

PMID- 22993066
TI  - The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin
      aldosterone system in response to low dietary salt intake in vivo.
AB  - Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been
      shown to be prerequisites for renal renin release after Na(+) deprivation. To
      answer the question of whether EP4 receptor type of PGE(2) mediates renin
      regulation under a low-salt diet, we examined renin regulation in EP4(+/+), EP4(
      /-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a
      low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+)
      excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and
      plasma electrolytes remained unchanged. EP4(-/-) exhibited a similar attenuation
      of Na(+) excretion; however, diuresis and K(+) excretion were enhanced, and
      plasma Na(+) concentration was higher, whereas plasma K(+) concentration was
      lower compared with control diet. There were no significant differences between
      EP4(+/+) and EP4(-/-) mice in blood pressure, creatinine clearance, and plasma
      antidiuretic hormone (ADH) concentration. Following salt restriction, plasma
      renin and aldosterone concentrations and kidney renin mRNA level rose
      significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with
      EP4 antagonist ONO-AE3-208. In the latter two groups, the low-salt diet caused a
      significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for
      COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in
      EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX
      2 followed by enhanced renal PGE(2) synthesis, which stimulates the renin
      angiotensin-aldosterone system by activation of EP4 receptor. Most likely,
      defects at the step of EP4 receptor block negative feedback mechanisms on the
      renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+)
      loss.

PMID- 22993067
TI  - Bicarbonate promotes BK-alpha/beta4-mediated K excretion in the renal distal
      nephron.
AB  - Ca-activated K channels (BK), which are stimulated by high distal nephron flow,
      are utilized during high-K conditions to remove excess K. Because BK
      predominantly reside with BK-beta4 in acid/base-transporting intercalated cells
      (IC), we determined whether BK-beta4 knockout mice (beta4KO) exhibit deficient K
      excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet
      (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-beta4
      expression increased (Western blot). When WT and beta4KO were placed on HK-Cl,
      plasma K concentration ([K]) was elevated compared with control K diets; however,
      K excretion was not different between WT and beta4KO. When HK-alk was consumed,
      the plasma [K] was lower and K clearance was greater in WT compared with beta4KO.
      The urine was alkaline in mice on HK-alk; however, urinary pH was not different
      between WT and beta4KO. Immunohistochemical analysis of pendrin and V-ATPase
      revealed the same increases in beta-IC, comparing WT and beta4KO on HK-alk. We
      found an amiloride-sensitive reduction in Na excretion in beta4KO, compared with
      WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to
      secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to
      minimize Na reabsorption exaggerated the defective K handling of beta4KO. When WT
      on LNaHK were given NH(4)Cl in the drinking water, K excretion was reduced to the
      magnitude of beta4KO on LNaHK. These results show that WT, but not beta4KO,
      efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-alpha/beta4
      mediated K secretion is promoted by bicarbonaturia.

PMID- 22993068
TI  - Renal cortical hemopexin accumulation in response to acute kidney injury.
AB  - Hemopexin (Hpx) is a liver-generated acute phase reactant that binds and
      neutralizes prooxidant free heme. This study tested whether acute kidney injury
      (AKI) triggers renal Hpx accumulation, potentially impacting heme Fe-mediated
      tubular injury. Mice were subjected to glycerol, cisplatin, ischemia-reperfusion
      (I/R), or endotoxemic [lipopolysaccharide (LPS)] AKI. In each instance, 3- to 30
      fold renal cortical and isolated proximal tubule segment (PTS) Hpx increases
      resulted. Although renal cortex and PTS showed variable Hpx mRNA increases, due,
      in part, to increased mRNA stability, mRNA levels did not correlate with renal
      Hpx protein accumulation. Conversely, AKI evoked three- to fourfold increases in
      hepatic Hpx gene induction, which corresponded with three- to fourfold plasma Hpx
      increases. Renal immunohistochemistry, and increased urinary Hpx excretion,
      indicated that circulating Hpx gains tubule luminal/urinary access, followed by
      proximal tubule endocytic uptake. Paradoxically, in cultured renal cells (HK-2,
      HEK-293), Fe depletion, and not free heme excess, increased Hpx mRNA. LPS acutely
      increased HK-2 cell Hpx mRNA. This finding, coupled with observations that LPS
      evoked ~30-fold greater renal Hpx mRNA increases than any other AKI model,
      suggests that inflammation, not heme exposure, activates the renal Hpx gene. Each
      form of AKI evoked early increases in circulating free heme, which subsequently
      fell to subnormal levels as plasma Hpx rose. In addition, purified Hpx blunted
      free Fe-mediated HK-2 cell death. In sum, these data indicated that AKI
      associated hepatic stress generates Hpx, which gains renal tubule access. Given
      its ability to bind free heme and mitigate free Fe toxicity, Hpx loading can
      potentially confer cytoprotective effects.

PMID- 22993070
TI  - Taking a sound approach to acute kidney injury.

PMID- 22993069
TI  - Mouse model of ischemic acute kidney injury: technical notes and tricks.
AB  - Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney
      disease associated with an increasing prevalence and high mortality rates. A
      variety of experimental models, both in vitro and in vivo, have been used to
      study the pathogenic mechanisms of ischemic AKI and to test renoprotective
      strategies. Among them, the mouse model of renal clamping is popular, mainly due
      to the availability of transgenic models and the relatively small animal size for
      drug testing. However, the mouse model is generally less stable, resulting in
      notable variations in results. Here, we describe a detailed protocol of the mouse
      model of bilateral renal ischemia-reperfusion. We share the lessons and
      experiences gained from our laboratory in the past decade. We further discuss the
      technical issues that account for the variability of this model and offer
      relevant solutions, which may help other investigators to establish a well
      controlled, reliable animal model of ischemic AKI.

PMID- 22993072
TI  - Landscape of ENaC regulation in the kidney.

PMID- 22993071
TI  - Connective tissue and its growth factor CTGF distinguish the morphometric and
      molecular remodeling of the bladder in a model of neurogenic bladder.
AB  - We previously reported that mice with experimental autoimmune encephalomyelitis
      (EAE), a model of multiple sclerosis (MS), develop profound urinary bladder
      dysfunction. Because neurogenic bladder in MS patients causes marked bladder
      remodeling, we next examined morphometric and molecular alterations of the
      bladder in EAE mice. EAE was created in female SJL/J mice by immunization with
      the p139-151 encephalitogenic peptide of myelin proteolipid protein in complete
      Freund's adjuvant, along with intraperitoneal injections of Bordetella pertussis
      toxin. Seventy days after immunization, mice were scored for the level of
      neurological impairment and then killed. Spinal cord sections were assessed for
      demyelination, inflammation, and T cell infiltration; the composition of the
      bladder tissue was measured quantitatively; and gene expression of markers of
      tissue remodeling and fibrosis was assessed. A significant increase in the
      bladder weight-to-body weight ratio was observed with increasing neurological
      impairment, and morphometric analysis showed marked bladder remodeling with
      increased luminal area and tissue hypertrophy. Despite increased amounts of all
      tissue components (urothelium, smooth muscle, and connective tissue), the ratio
      of connective tissue to muscle increased significantly in EAE mice compared with
      control mice. Marked increases in mRNA expression of collagen type I alpha(2),
      tropoelastin, transforming growth factor-beta3, and connective tissue growth
      factor (CTGF) were observed in EAE mice, as were decreased levels of mRNAs for
      smooth muscle myosin heavy chain, nerve growth factors, and muscarinic and
      purinergic receptors. Our results suggest that bladder remodeling corresponding
      to EAE severity may be due to enhanced expression of CTGF and increased growth of
      connective tissue.

PMID- 22993073
TI  - Increased production of superoxide anion contributes to dysfunction of the
      arteriovenous fistula.
AB  - Vascular access dysfunction causes morbidity in hemodialysis patients. This study
      examined the generation and pathobiological significance of superoxide anion in a
      rat femoral arteriovenous fistula (AVF). One week after AVF creation, there was
      increased production of superoxide anion accompanied by decreased total
      superoxide dismutase (SOD) and Cu/Zn SOD activities and induction of the redox
      sensitive gene heme oxygenase-1. Immunohistochemical studies of nitrotyrosine
      formation demonstrated that peroxynitrite, a product of superoxide anion and
      nitric oxide, was present in increased amounts in endothelial and smooth muscle
      cells in the AVF. Because uncoupled NOS isoforms generate superoxide anion, and
      NOS coupling requires tetrahydrobiopterin (BH(4)) as a cofactor, we assessed NOS
      uncoupling by determining the ratio of BH(4) to dihydrobiopterin (BH(2)); the
      BH(4)-to-BH(2) ratio was markedly attenuated in the AVF. Because Src is a
      vasculopathic signaling species upstream and downstream of superoxide anion, such
      expression was evaluated; expression of Src and phosphorylated Src was both
      markedly increased in the AVF. Expression of NADPH oxidase (NOX) 1, NOX2, NOX4,
      cyclooxygenase (COX) 1, COX2, p47(phox), and p67(phox) was all unchanged, as
      assessed by Western analyses, thereby suggesting that these proteins may not be
      involved in increased production of superoxide anion. Finally, administration of
      tempol, a superoxide anion scavenger, decreased neointima formation in the juxta
      anastomotic venous segment and improved AVF blood flow. We conclude that the AVF
      exhibits increased superoxide anion generation that may reflect the combined
      effects of decreased scavenging by SOD and increased generation by uncoupled NOS,
      and that enhanced superoxide anion production promotes juxta-anastomotic stenosis
      and impairs AVF function.

PMID- 22993074
TI  - Elevated steady-state bladder preload activates myosin phosphorylation: detrusor
      smooth muscle is a preload tension sensor.
AB  - In rabbit bladder wall (detrusor) muscle, the degree of tone induced during
      physiological filling (filling tone) is the sum of adjustable preload tension and
      autonomous contractile tension. The present study was designed to determine
      whether the level of filling tone is dependent on detrusor muscle length. Maximum
      active tension induced by KCl was parabolic in relation to length [tension
      increased from 70% to 100% of a reference length (L(ref)) and decreased at longer
      muscle lengths]. Filling tone, however, increased in a linear fashion from 70% to
      120% L(ref). In the presence of ibuprofen to abolish autonomous contraction and
      retain adjustable preload tension, tension was reduced in strength but remained
      linearly dependent on length from 70% to 120% L(ref). In the absence of
      autonomous contraction, stretching detrusor muscle from 80% to 120% L(ref) still
      caused an increase in tone during PGE(2)-induced rhythmic contraction, suggesting
      that muscle stretch caused increases in detrusor muscle contractile sensitivity
      rather than in prostaglandin release. In the absence of autonomous contraction,
      the degree of adjustable preload tension and myosin phosphorylation increased
      when detrusor was stretched from 80% to 120% L(ref), but also displayed length
      hysteresis, indicating that detrusor muscle senses preload rather than muscle
      length. Together, these data support the hypothesis that detrusor muscle acts as
      a preload tension sensor. Because detrusor muscle is in-series with neuronal
      mechanosensors responsible for urinary urgency, a more thorough understanding of
      detrusor muscle filling tone may reveal unique targets for therapeutic
      intervention of contractile disorders such as overactive bladder.

PMID- 22993075
TI  - In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis.
AB  - Nephrolithiasis is a major public health problem with a complex and varied
      etiology. Most stones are composed of calcium oxalate (CaOx), with dietary excess
      a risk factor. Because of complexity of mammalian system, the details of stone
      formation remain to be understood. Here we have developed a nephrolithiasis model
      using the genetic model Drosophila melanogaster, which has a simple, transparent
      kidney tubule. Drosophilia reliably develops CaOx stones upon dietary oxalate
      supplementation, and the nucleation and growth of microliths can be viewed in
      real time. The Slc26 anion transporter dPrestin (Slc26a5/6) is strongly expressed
      in Drosophilia kidney, and biophysical analysis shows that it is a potent oxalate
      transporter. When dPrestin is knocked down by RNAi in fly kidney, formation of
      microliths is reduced, identifying dPrestin as a key player in oxalate excretion.
      CaOx stone formation is an ancient conserved process across >400 My of divergent
      evolution (fly and human), and from this study we can conclude that the fly is a
      good genetic model of nephrolithiasis.

PMID- 22993076
TI  - Are ocular complications of a high-dose glucocorticoid treatment appropriately
      monitored in patients with rheumatic diseases?
AB  - Glucocorticoid is frequently used in treating various rheumatic conditions.
      However it is known to cause multiple toxicities including cataract or glaucoma.
      In this study, we examined whether patients with rheumatic diseases had
      appropriate ocular monitoring for glucocorticoid toxicities. From rheumatology
      clinics in South New Jersey of the USA, we retrospectively identified patients
      with ages between 18 and 60 years old who received a high accumulative dose of
      glucocorticoid, which was defined as glucocorticoid dose greater than prednisone
      7.5mg/day * 6 months = 1,350 mg. We observed rheumatologists recommended eye
      examinations only in 14/37 (37.8 %) of patients. Family history was present for
      cataract in 13/37 (35.1 %) patients and for glaucoma in 6/37 (16.2 %) patients.
      Rheumatologists recommended eye examinations in 4/13 (30.7 %) and 0/6 (0 %)
      patients in each group. This study suggested that rheumatologists did not
      appropriately monitor ocular complications of a high dose glucocorticoid, even in
      patients with a positive family history. 

PMID- 22993078
TI  - Needle-knife precut papillotomy with a small incision over a pancreatic stent
      improves the success rate and reduces the complication rate in difficult biliary
      cannulations.
AB  - BACKGROUND: Successful precut sphincterotomy (PS) in difficult biliary
      cannulation (DBC) requires a large incision for deroofing the papilla. However,
      the high complication rate poses a substantial problem, in addition to the need
      for expert skills. Pancreatic stent placement could facilitate this procedure.
      Needle-knife precut papillotomy with a small incision using a layer-by-layer
      method over a pancreatic stent (NKPP-SIPS) could potentially improve the success
      rate and reduce the complication rate of PS. AIMS: To validate the efficacy,
      feasibility and safety of NKPP-SIPS in DBC. METHODS: Therapeutic endoscopic
      retrograde cholangiopancreatography with a naive papilla was performed in 1619
      cases between May 2004 and July 2011. We prospectively divided the patients
      chronologically, in terms of the period during which the procedure was performed,
      into two groups: group A; needle-knife precut papillotomy (NKPP) performed
      between April 2004 and October 2006; group B; NKPP-SIPS performed between
      November 2006 and July 2011. The success rates and complication rates were
      evaluated. NKPP was performed without pancreatic stent placement and the cut was
      made starting at the papillary orifice, extended upward over a length of more
      than 5-10 mm for deroofing the papilla. On the other hand, in NKPP-SIPS, a
      pancreatic stent was placed initially as a guide, and to prevent post-ERCP
      pancreatitis, the incision was begun at the papillary orifice in a layer-by-layer
      fashion and extended upward in 1-2 mm increments, not going beyond the oral
      protrusion, finally measuring less than 5 mm in length. RESULTS: PS was performed
      in 8.3 % of the patients (134/1619). The cannulation success rate of PS in the
      entire group was 94.0 % (126/134). NKPP and NKPP-SIPS were performed in 36 and 98
      of the patients, respectively. There was one case of major bleeding in group A,
      and no severe complications in group B. The success rates of bile duct
      cannulation increased from 86.1 % (31/36) in group A to 96.9 % (95/98) in group B
      (p = 0.0189). The overall complication rate of PS was YC 33 % (12/36) in group A
      (major bleeding 8.3 %; mild to moderate pancreatitis 19.4 %; perforation
      requiring surgery 2.8 %), and 7.1 % (7/98) in group B (mild to moderate
      pancreatitis 6.1 %; minor perforation 1 %) (p < 0.001). CONCLUSIONS: NKPP-SIPS
      has significantly improved the success rate and reduced the complication rate of
      DBC, proving that a small incision starting at the orifice of the PS is
      sufficient, feasible and safe in DBC, when a pancreatic stent is inserted at the
      outset.

PMID- 22993077
TI  - Enhancing the effectiveness of androgen deprivation in prostate cancer by
      inducing Filamin A nuclear localization.
AB  - As prostate cancer (CaP) is regulated by androgen receptor (AR) activity,
      metastatic CaP is treated with androgen deprivation therapy (ADT). Despite
      initial response, patients on ADT eventually progress to castration-resistant CaP
      (CRPC), which is currently incurable. We previously showed that cleavage of the
      280 kDa structural protein Filamin A (FlnA) to a 90 kDa fragment, and nuclear
      localization of the cleaved product, sensitized CRPC cells to ADT. Hence,
      treatment promoting FlnA nuclear localization would enhance androgen
      responsiveness. Here, we show that FlnA nuclear localization induced apoptosis in
      CRPC cells during ADT, identifying it as a treatment tool in advanced CaP.
      Significantly, the natural product genistein combined polysaccharide (GCP) had a
      similar effect. Investigation of the mechanism of GCP-induced apoptosis showed
      that GCP induced FlnA cleavage and nuclear localization and that apoptosis
      resulting from GCP treatment was mediated by FlnA nuclear localization. Two main
      components of GCP are genistein and daidzein: the ability of GCP to induce G2
      arrest was due to genistein whereas sensitivity to ADT stemmed from daidzein;
      hence, both were needed to mediate GCP's effects. FlnA cleavage is regulated by
      its phosphorylation; we show that ADT enhanced FlnA phosphorylation, which
      prevented its cleavage, whereas GCP inhibited FlnA phosphorylation, thereby
      sensitizing CaP cells to ADT. In a mouse model of CaP recurrence, GCP, but not
      vehicle, impeded relapse following castration, indicating that GCP, when
      administered with ADT, interrupted the development of CRPC. These results
      demonstrate the efficacy of GCP in promoting FlnA nuclear localization and
      enhancing androgen responsiveness in CaP.

PMID- 22993079
TI  - Phlorofucofuroeckol A suppresses expression of inducible nitric oxide synthase,
      cyclooxygenase-2, and pro-inflammatory cytokines via inhibition of nuclear factor
      kappaB, c-Jun NH2-terminal kinases, and Akt in microglial cells.
AB  - Microglial activation has been implicated in many neurological disorders for its
      inflammatory and neurotrophic effects. In this study, we investigated the effects
      of phlorofucofuroeckol A isolated from Ecklonia stolonifera Okamura on the
      production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated
      microglia. Pre-treatment of phlorofucofuroeckol A attenuated the productions of
      nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in LPS-stimulated
      microglia. Profoundly, phlorofucofuroeckol A treatment showed inactivation of
      nuclear factor-kappaB (NF-kappaB) by preventing the degradation of inhibitor
      kappaB-alpha and the nuclear translocation of p65 NF-kappaB subunit. Moreover,
      phlorofucofuroeckol A inhibited the activation of c-Jun NH2-terminal kinases
      (JNKs), p38 mitogen-activated protein kinase (MAPK), and Akt, but not that of
      extracellular signal-regulated kinase. These results indicate that
      phlorofucofuroeckol A inhibits the LPS-induced expression of inflammatory
      mediators through inactivation of NF-kappaB, JNKs, p38 MAPK, and Akt pathways.
      These findings suggest that phlorofucofuroeckol A can be considered as a
      nutraceutical candidate for the treatment of neuroinflammation in
      neurodegenerative diseases.

PMID- 22993080
TI  - The structures of T6, T3R3 and R6 bovine insulin: combining X-ray diffraction and
      absorption spectroscopy.
AB  - The crystal structures of three conformations, T(6), T(3)R(3) and R(6), of bovine
      insulin were solved at 1.40, 1.30 and 1.80 A resolution, respectively. All
      conformations crystallized in space group R3. In contrast to the T(6) and
      T(3)R(3) structures, different conformations of the N-terminal B-chain residue
      PheB1 were observed in the R(6) insulin structure, resulting in an eightfold
      doubling of the unit-cell volume upon cooling. The zinc coordination in each
      conformation was studied by X-ray absorption spectroscopy (XAS), including both
      EXAFS and XANES. Zinc adopts a tetrahedral coordination in all R(3) sites and an
      octahedral coordination in T(3) sites. The coordination distances were refined
      from XAS with a standard deviation of <0.01 A. In contrast to the distances
      determined from the medium-resolution crystal structures, the XAS results were in
      good agreement with similar coordination geometries found in small molecules, as
      well as in other high-resolution insulin structures. As the radiation dose for
      XRD experiments is two orders of magnitude higher compared with that of XAS
      experiments, the single crystals were exposed to a higher degree of radiation
      damage that affected the zinc coordination in the T(3) sites in particular.
      Furthermore, XANES spectra for the zinc sites in T(6) and R(6) insulin were
      successfully calculated using finite difference methods and the bond distances
      and angles were optimized from a quantitative XANES analysis.

PMID- 22993081
TI  - Contamination from an affinity column: an encounter with a new villain in the
      world of membrane-protein crystallization.
AB  - Attempts to crystallize AtNTT1, a chloroplast ATP/ADP transporter from
      Arabidopsis thaliana, revealed an unexpected contaminant, Strep-Tactin, a variant
      of streptavidin that was used during purification of the protein. Although it was
      present in very small amounts, crystals of Strep-Tactin were reproducibly grown
      from the AtNTT1 solution. AtNTT1 was overexpressed in Escherichia coli and
      purified from detergent-solubilized membrane fractions using Strep-Tactin
      affinity chromatography based on an engineered streptavidin. The contamination of
      protein solutions purified on Strep-Tactin columns has never been described
      previously and seems to be specific to membrane proteins solubilized in
      detergents. Trace amounts of Strep-Tactin were observed to be eluted from a Strep
      Tactin column using several routinely used detergents, illustrating their
      possible role in the contamination. This finding raises an alarm and suggests
      caution in membrane-protein purification using Strep-Tactin affinity columns,
      where detergents are essential components. The small crystals of contaminant
      protein led to the structure at 1.9 A resolution of Strep-Tactin in complex with
      desthiobiotin.

PMID- 22993082
TI  - Structures of bovine, equine and leporine serum albumin.
AB  - Serum albumin first appeared in early vertebrates and is present in the plasma of
      all mammals. Its canonical structure supported by a conserved set of disulfide
      bridges is maintained in all mammalian serum albumins and any changes in sequence
      are highly correlated with evolution of the species. Previous structural
      investigations of mammalian serum albumins have only concentrated on human serum
      albumin (HSA), most likely as a consequence of crystallization and diffraction
      difficulties. Here, the crystal structures of serum albumins isolated from
      bovine, equine and leporine blood plasma are reported. The structure of bovine
      serum albumin (BSA) was determined at 2.47 A resolution, two crystal structures
      of equine serum albumin (ESA) were determined at resolutions of 2.32 and 2.04 A,
      and that of leporine serum albumin (LSA) was determined at 2.27 A resolution.
      These structures were compared in detail with the structure of HSA. The ligand
      binding pockets in BSA, ESA and LSA revealed different amino-acid compositions
      and conformations in comparison to HSA in some cases; however, much more
      significant differences were observed on the surface of the molecules. BSA, which
      is one of the most extensively utilized proteins in laboratory practice and is
      used as an HSA substitute in many experiments, exhibits only 75.8% identity
      compared with HSA. The higher resolution crystal structure of ESA highlights the
      binding properties of this protein because it includes several bound compounds
      from the crystallization solution that provide additional structural information
      about potential ligand-binding pockets.

PMID- 22993083
TI  - The 1.2 A resolution crystal structure of TcpG, the Vibrio cholerae DsbA
      disulfide-forming protein required for pilus and cholera-toxin production.
AB  - The enzyme TcpG is a periplasmic protein produced by the Gram-negative pathogen
      Vibrio cholerae. TcpG is essential for the production of ToxR-regulated proteins,
      including virulence-factor pilus proteins and cholera toxin, and is therefore a
      target for the development of a new class of anti-virulence drugs. Here, the 1.2
      A resolution crystal structure of TcpG is reported using a cryocooled crystal.
      This structure is compared with a previous crystal structure determined at 2.1 A
      resolution from data measured at room temperature. The new crystal structure is
      the first DsbA crystal structure to be solved at a sufficiently high resolution
      to allow the inclusion of refined H atoms in the model. The redox properties of
      TcpG are also reported, allowing comparison of its oxidoreductase activity with
      those of other DSB proteins. One of the defining features of the Escherichia coli
      DsbA enzyme is its destabilizing disulfide, and this is also present in TcpG. The
      data presented here provide new insights into the structure and redox properties
      of this enzyme, showing that the binding mode identified between E. coli DsbB and
      DsbA is likely to be conserved in TcpG and that the beta5-alpha7 loop near the
      proposed DsbB binding site is flexible, and suggesting that the tense oxidized
      conformation of TcpG may be the consequence of a short contact at the active site
      that is induced by disulfide formation and is relieved by reduction.

PMID- 22993084
TI  - Various cross-reactivity of the grass pollen group 4 allergens: crystallographic
      study of the Bermuda grass isoallergen Cyn d 4.
AB  - The structure of Cyn d 4, the group 4 allergen from Bermuda grass, is reported at
      2.15 A resolution and is the first crystal structure of a naturally isolated
      pollen allergen. A conserved N-terminal segment that is only present in the large
      isoallergens forms extensive interactions with surrounding residues and hence
      greatly enhances the structural stability of the protein. Cyn d 4 contains an FAD
      cofactor that is covalently linked to His88 and Cys152. To date, all identified
      bicovalent flavoproteins are oxidases and their substrates are either sugars or
      secondary metabolites. A deep large hydrophobic substrate-binding cleft is
      present. Thus, Cyn d 4 may be an oxidase that is involved in the biosynthesis of
      a pollen-specific metabolite. Cyn d 4 shares ~70% sequence identity with the
      Pooideae group 4 allergens. Various cross-reactivities between grass pollen group
      4 allergens have previously been demonstrated using sera from allergic patients.
      The protein surface displays an unusually large number of positively charged
      clusters, reflecting the high pI of ~10. 38 decapeptides that cover the solvent
      accessible sequences did not show any significant IgE-binding activity using sera
      with high Cyn d 4 reactivity from four patients, suggesting that the IgE epitopes
      of Cyn d 4 are predominantly conformational in nature. Several group 4 structures
      were then modelled and their potential cross-reactive and species-specific IgE
      epitopes were proposed.

PMID- 22993085
TI  - The structure of the ternary Eg5-ADP-ispinesib complex.
AB  - The human kinesin Eg5 is responsible for bipolar spindle formation during early
      mitosis. Inhibition of Eg5 triggers the formation of monoastral spindles, leading
      to mitotic arrest that eventually causes apoptosis. There is increasing evidence
      that Eg5 constitutes a potential drug target for the development of cancer
      chemotherapeutics. The most advanced Eg5-targeting agent is ispinesib, which
      exhibits potent antitumour activity and is currently in multiple phase II
      clinical trials. In this study, the crystal structure of the Eg5 motor domain in
      complex with ispinesib, supported by kinetic and thermodynamic binding data, is
      reported. Ispinesib occupies the same induced-fit pocket in Eg5 as other
      allosteric inhibitors, making extensive hydrophobic interactions with the
      protein. The data for the Eg5-ADP-ispinesib complex suffered from pseudo
      merohedral twinning and revealed translational noncrystallographic symmetry,
      leading to challenges in data processing, space-group assignment and structure
      solution as well as in refinement. These complications may explain the lack of
      available structural information for this important agent and its analogues. The
      present structure represents the best interpretation of these data based on
      extensive data-reduction, structure-solution and refinement trials.

PMID- 22993086
TI  - Structure of FabH and factors affecting the distribution of branched fatty acids
      in Micrococcus luteus.
AB  - Micrococcus luteus is a Gram-positive bacterium that produces iso- and anteiso
      branched alkenes by the head-to-head condensation of fatty-acid thioesters
      [coenzyme A (CoA) or acyl carrier protein (ACP)]; this activity is of interest
      for the production of advanced biofuels. In an effort to better understand the
      control of the formation of branched fatty acids in M. luteus, the structure of
      FabH (MlFabH) was determined. FabH, or beta-ketoacyl-ACP synthase III, catalyzes
      the initial step of fatty-acid biosynthesis: the condensation of malonyl-ACP with
      an acyl-CoA. Analysis of the MlFabH structure provides insights into its
      substrate selectivity with regard to length and branching of the acyl-CoA. The
      most structurally divergent region of FabH is the L9 loop region located at the
      dimer interface, which is involved in the formation of the acyl-binding channel
      and thus limits the substrate-channel size. The residue Phe336, which is
      positioned near the catalytic triad, appears to play a major role in branched
      substrate selectivity. In addition to structural studies of MlFabH,
      transcriptional studies of M. luteus were also performed, focusing on the
      increase in the ratio of anteiso:iso-branched alkenes that was observed during
      the transition from early to late stationary phase. Gene-expression microarray
      analysis identified two genes involved in leucine and isoleucine metabolism that
      may explain this transition.

PMID- 22993087
TI  - Structural insight into the ISC domain of VibB from Vibrio cholerae at atomic
      resolution: a snapshot just before the enzymatic reaction.
AB  - The N-terminal isochorismatase (ISC) domain of VibB (VibB-ISC) catalyzes the
      vinyl ether hydrolysis of isochorismate to 2,3-dihydro-2,3-dihydroxybenzoate and
      pyruvate. Structures of the ISC domain and its complex with isochorismate have
      been determined at 1.35 and 1.10 A resolution, respectively. Two catalytic waters
      which were absent from previously reported homologous structures were observed
      adjacent to isochorismate and the catalytic residues (Asp35 and Lys118) in the
      VibB-ISC complex. Molecular-dynamics (MD) simulations starting with the structure
      of the VibB-ISC complex suggest that the catalytic waters contribute to the
      hydrolysis of the vinyl ether by participating in two reactions. Firstly, they
      may function as a general acid to protonate the Asp35 carboxylate prior to
      isochorismate protonation; secondly, one of the catalytic waters may be activated
      by the ionizable side chain of Asp35 to perform a nucleophilic attack on the
      intermediate carbocation/oxocarbonium ion. The positions of the waters are both
      significantly affected by the mutation of Asp35 and Lys118. The structural,
      biochemical and MD results reveal the residues that are involved in substrate
      binding and provide clues towards defining a possible mechanism.

PMID- 22993088
TI  - The accessory domain changes the accessibility and molecular topography of the
      catalytic interface in monomeric GH39 beta-xylosidases.
AB  - beta-Xylosidases (EC 3.2.1.37) are among the principal glycosyl hydrolases
      involved in the breakdown of hemicelluloses, catalyzing the reduction of
      xylooligosaccharides to free xylose. All GH39 beta-xylosidases structurally
      characterized to date display a modular multi-domain organization that assembles
      a tetrameric quaternary structure. In this work, the crystal structure and the
      SAXS molecular envelope of a new GH39 beta-xylosidase from Caulobacter crescentus
      (CcXynB2) have been determined. Interestingly, CcXynB2 is a monomer in solution
      and comparative structural analyses suggest that the shortened C-terminus
      prevents the formation of a stable tetramer. Moreover, CcXynB2 has a longer loop
      from the auxiliary domain (the long alpha-helix-containing loop) which makes a
      number of polar and hydrophobic contacts with the parental (alpha/beta)(8)-barrel
      domain, modifying the accessibility and the molecular topography of the catalytic
      interface. These interactions also maintain the accessory domain tightly linked
      to the catalytic core, which may be important for enzyme function and stability.

PMID- 22993089
TI  - Pattern prediction and coordination geometry analysis from cadmium-binding
      proteins: a computational approach.
AB  - Cadmium toxicity has been reported to have major health effects including
      carcinogenicity, respiratory disorders, kidney failure, neurotoxicity and liver
      dysfunction. Understanding the nature of the association of cadmium with
      biomolecules has thus become imperative and a key factor in predicting the
      phenomena behind predisposition to disease. Accordingly, a computational
      investigation of cadmium-binding characteristics was performed using about 140
      cadmium-bound structures and 34 cadmium-binding sequences. The metal-coordinating
      architecture defining the chelate loops, residue arrangement, secondary
      structural characteristics, distances and angles were analyzed. Binding patterns
      were predicted based on the probability of occurrence of residues within the
      coordination distance and were further corroborated with sequence patterns
      obtained from cadmium-binding proteins. About 56 different chelate loops were
      identified. Based on these chelate loops, putative cadmium-binding patterns were
      derived that resembled short-length motifs, namely Y-X-G-X-G, Q-X(9)-E, E-X(2)-E
      X(2)-E and T-X(5)-E-X(2)-E, which were observed within the conserved regions of
      the cadmium-binding proteins. The poorer conservation of residues around these
      motifs resulted in a deviating pattern against the coordination loops. These
      structure-based motifs are proposed to be an efficient tool in building chelators
      for the effective removal of cadmium.

PMID- 22993091
TI  - Crystallization, dehydration and experimental phasing of WbdD, a bifunctional
      kinase and methyltransferase from Escherichia coli O9a.
AB  - WbdD is a bifunctional kinase/methyltransferase that is responsible for
      regulation of lipopolysaccharide O antigen polysaccharide chain length in
      Escherichia coli serotype O9a. Solving the crystal structure of this protein
      proved to be a challenge because the available crystals belonging to space group
      I23 only diffracted to low resolution (>95% of the crystals diffracted to
      resolution lower than 4 A and most only to 8 A) and were non-isomorphous, with
      changes in unit-cell dimensions of greater than 10%. Data from a serendipitously
      found single native crystal that diffracted to 3.0 A resolution were non
      isomorphous with a lower (3.5 A) resolution selenomethionine data set. Here, a
      strategy for improving poor (3.5 A resolution) initial phases by density
      modification and cross-crystal averaging with an additional 4.2 A resolution data
      set to build a crude model of WbdD is desribed. Using this crude model as a mask
      to cut out the 3.5 A resolution electron density yielded a successful molecular
      replacement solution of the 3.0 A resolution data set. The resulting map was used
      to build a complete model of WbdD. The hydration status of individual crystals
      appears to underpin the variable diffraction quality of WbdD crystals. After the
      initial structure had been solved, methods to control the hydration status of
      WbdD were developed and it was thus possible to routinely obtain high-resolution
      diffraction (to better than 2.5 A resolution). This novel and facile crystal
      dehydration protocol may be useful for similar challenging situations.

PMID- 22993090
TI  - Structural characterization and comparison of three acyl-carrier-protein
      synthases from pathogenic bacteria.
AB  - Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to
      be important candidates for drug discovery. The scientific and medical quest for
      new FAS II protein targets continues to stimulate research in this field. One of
      the possible additional candidates is the acyl-carrier-protein synthase (AcpS)
      enzyme. Its holo form post-translationally modifies the apo form of an acyl
      carrier protein (ACP), which assures the constant delivery of thioester
      intermediates to the discrete enzymes of FAS II. At the Center for Structural
      Genomics of Infectious Diseases (CSGID), AcpSs from Staphylococcus aureus
      (AcpS(SA)), Vibrio cholerae (AcpS(VC)) and Bacillus anthracis (AcpS(BA)) have
      been structurally characterized in their apo, holo and product-bound forms,
      respectively. The structure of AcpS(BA) is emphasized because of the two 3',5'
      adenosine diphosphate (3',5'-ADP) product molecules that are found in each of the
      three coenzyme A (CoA) binding sites of the trimeric protein. One 3',5'-ADP is
      bound as the 3',5'-ADP part of CoA in the known structures of the CoA-AcpS and
      3',5'-ADP-AcpS binary complexes. The position of the second 3',5'-ADP has never
      been described before. It is in close proximity to the first 3',5'-ADP and the
      ACP-binding site. The coordination of two ADPs in AcpS(BA) may possibly be
      exploited for the design of AcpS inhibitors that can block binding of both CoA
      and ACP.

PMID- 22993092
TI  - Structural polymorphism of c-di-GMP bound to an EAL domain and in complex with a
      type II PilZ-domain protein.
AB  - Cyclic di-GMP (c-di-GMP) is a novel secondary-messenger molecule that is involved
      in regulating a plethora of important bacterial activities through binding to an
      unprecedented array of effectors. Proteins with a canonical PilZ domain that bind
      c-di-GMP play crucial roles in regulating flagellum-based motility. In contrast,
      noncanonical type II PilZ domains that do not effectively bind c-di-GMP regulate
      twitching motility, which is dependent on type IV pili (T4P). Recent data
      indicate that T4P biogenesis is initiated via the interaction of a noncanonical
      type II PilZ protein with the GGDEF/EAL-domain protein FimX and the pilus motor
      protein PilB at high c-di-GMP concentrations. However, the molecular details of
      such interactions remain to be elucidated. In this manuscript, the first hetero
      complex crystal structure between a type II PilZ protein and the EAL domain of
      the FimX protein (FimX(EAL)) from Xanthomonas campestris pv. campestris (Xcc) in
      the presence of c-di-GMP is reported. This work reveals two novel conformations
      of monomeric c-di-GMP in the XccFimX(EAL)-c-di-GMP and XccFimX(EAL)-c-di-GMP
      XccPilZ complexes, as well as a unique interaction mode of a type II PilZ domain
      with FimX(EAL). These findings indicate that c-di-GMP is sufficiently flexible to
      adjust its conformation to match the corresponding recognition motifs of
      different cognate effectors. Together, these results represent a first step
      towards an understanding of how T4P biogenesis is controlled by c-di-GMP at the
      molecular level and also of the ability of c-di-GMP to bind to a wide variety of
      effectors.

PMID- 22993093
TI  - CrystalDirect: a new method for automated crystal harvesting based on laser
      induced photoablation of thin films.
AB  - The use of automated systems for crystallization and X-ray data collection is now
      widespread. However, these two steps are separated by the need to transfer
      crystals from crystallization supports to X-ray data-collection supports, which
      is a difficult manual operation. Here, a new approach is proposed called
      CrystalDirect (CD) which enables full automation of the crystal-harvesting
      process. In this approach, crystals are grown on ultrathin films in a newly
      designed vapour-diffusion crystallization plate and are recovered by excision of
      the film through laser-induced photoablation. The film pieces containing crystals
      are then directly attached to a pin for X-ray data collection. This new method
      eliminates the delicate step of 'crystal fishing', thereby enabling full
      automation of the crystal-mounting process. Additional advantages of this
      approach include the absence of mechanical stress and that it facilitates
      handling of microcrystals. The CD crystallization plates are also suitable for in
      situ crystal screening with minimal X-ray background. This method could enable
      the operational integration of highly automated crystallization and data
      collection facilities, minimizing the delay between crystal identification and
      diffraction measurements. It can also contribute significantly to the advancement
      of challenging projects that require the systematic testing of large numbers of
      crystals.

PMID- 22993094
TI  - Structure of a thermophilic cyanobacterial b6f-type Rieske protein.
AB  - The 'Rieske protein' PetC is one of the key subunits of the cytochrome b(6)f
      complex. Its Rieske-type [2Fe-2S] cluster participates in the photosynthetic
      electron-transport chain. Overexpression and careful structure analysis at 2.0 A
      resolution of the extrinsic soluble domain of PetC from the thermophilic
      cyanobacterium Thermosynechococcus elongatus BP-1 enabled in-depth spectroscopic
      and structural characterization and suggested novel structural features. In
      particular, both the protein structure and the positions of the internal water
      molecules unexpectedly showed a higher similarity to eukaryotic PetCs than to
      other prokaryotic PetCs. The structure also revealed a deep pocket on the PetC
      surface which is oriented towards the membrane surface in the whole complex. Its
      surface properties suggest a binding site for a hydrophobic compound and the
      complete conservation of the pocket-forming residues in all known PetC sequences
      indicates the functional importance of this pocket in the cytochrome b(6)f
      complex.

PMID- 22993095
TI  - Structure of the autophagic E2 enzyme Atg10.
AB  - Autophagy is a regulated degradation pathway that plays a critical role in all
      eukaryotic life cycles. One interesting feature of the core autophagic process,
      autophagosome formation, is similar to ubiquitination. One of two autophagic E2
      enzymes, Atg10, interacts with Atg7 to receive Atg12, a ubiquitin-like molecule,
      and is also involved in the Atg12-Atg5 conjugation reaction. To date, no
      information on the interaction between Atg10 and Atg7 has been reported, although
      structural information is available pertaining to the individual components.
      Here, the crystal structure of Atg10 from Saccharomyces cerevisiae is described
      at 2.7 A resolution. A significant improvement of the diffraction limit by heavy
      atom derivatization was essential for structure determination. The core fold of
      yeast Atg10 is well conserved compared with those of Atg3 and other E2 enzymes.
      In contrast to other E2 enzymes, however, the autophagic E2 enzymes Atg3 and
      Atg10 possess insertion regions in the middle of the core fold and may be
      involved in protein function. The missing segment, which was termed the 'FR
      region', in Atg10 may be important for interaction with the E1 enzyme Atg7. This
      study provides a framework for understanding the E2 conjugation reaction in
      autophagy.

PMID- 22993096
TI  - Structure of the CFA/III major pilin subunit CofA from human enterotoxigenic
      Escherichia coli determined at 0.90 A resolution by sulfur-SAD phasing.
AB  - CofA, a major pilin subunit of colonization factor antigen III (CFA/III), forms
      pili that mediate small-intestinal colonization by enterotoxigenic Escherichia
      coli (ETEC). In this study, the crystal structure of an N-terminally truncated
      version of CofA was determined by single-wavelength anomalous diffraction (SAD)
      phasing using five sulfurs in the protein. Given the counterbalance between
      anomalous signal strength and the undesired X-ray absorption of the solvent,
      diffraction data were collected at 1.5 A resolution using synchrotron radiation.
      These data were sufficient to elucidate the sulfur substructure at 1.38 A
      resolution. The low solvent content (29%) of the crystal necessitated that
      density modification be performed with an additional 0.9 A resolution data set to
      reduce the phase error caused by the small sulfur anomalous signal. The CofA
      structure showed the alphabeta-fold typical of type IVb pilins and showed high
      structural homology to that of TcpA for toxin-coregulated pili of Vibrio
      cholerae, including spatial distribution of key residues critical for pilin self
      assembly. A pilus-filament model of CofA was built by computational docking and
      molecular-dynamics simulation using the previously reported filament model of
      TcpA as a structural template. This model revealed that the CofA filament surface
      was highly negatively charged and that a 23-residue-long loop between the alpha1
      and alpha2 helices filled the gap between the pilin subunits. These
      characteristics could provide a unique binding epitope for the CFA/III pili of
      ETEC compared with other type IVb pili.

PMID- 22993097
TI  - How good can our beamlines be?
AB  - The accuracy of X-ray diffraction data depends on the properties of the
      crystalline sample and on the performance of the data-collection facility
      (synchrotron beamline elements, goniostat, detector etc.). However, it is
      difficult to evaluate the level of performance of the experimental setup from the
      quality of data sets collected in rotation mode, as various crystal properties
      such as mosaicity, non-uniformity and radiation damage affect the measured
      intensities. A multiple-image experiment, in which several analogous diffraction
      frames are recorded consecutively at the same crystal orientation, allows
      minimization of the influence of the sample properties. A series of 100
      diffraction images of a thaumatin crystal were measured on the SBC beamline 19BM
      at the APS (Argonne National Laboratory). The obtained data were analyzed in the
      context of the performance of the data-collection facility. An objective way to
      estimate the uncertainties of individual reflections was achieved by analyzing
      the behavior of reflection intensities in the series of analogous diffraction
      images. The multiple-image experiment is found to be a simple and adequate method
      to decompose the random errors from the systematic errors in the data, which
      helps in judging the performance of a data-collection facility. In particular,
      displaying the intensity as a function of the frame number allows evaluation of
      the stability of the beam, the beamline elements and the detector with minimal
      influence of the crystal properties. Such an experiment permits evaluation of the
      highest possible data quality potentially achievable at the particular beamline.

PMID- 22993100
TI  - Relationship between recommended chronic heart failure treatments and mortality
      over 8 years in real-world conditions: a pharmacoepidemiological study.
AB  - PURPOSE: We previously reported that chronic heart failure (CHF) treatments
      reduce the duration of hospitalisation, even in elderly patients. The present
      study aimed to determine whether CHF treatment also provides long-term benefits
      in terms of reduced mortality at 8 years. METHODS: A cohort of 281 patients who
      were admitted to a French teaching hospital with a main diagnosis of CHF were
      followed through the health insurance databases for 1 year and through the
      national mortality database for 8 years. RESULTS: Diuretics (236 patients, 84 %)
      and angiotensin-converting enzyme (ACE) inhibitors (193 patients, 69 %) were the
      most-frequently prescribed medications. The median duration of survival was 46
      months. Mortality rates were significantly lower for patients administered beta
      blockers (59 %) and statins (56 %) than for patients not exposed to these drugs
      (82 %, p < 0.001 and 78 %, p = 0.001 respectively). No significant differences in
      mortality were observed for spironolactone, diuretics or ACE inhibitors. After
      adjustment, beta-blocker treatment remained associated with a significantly lower
      risk of mortality (hazard ratio, HR = 0.54 [0.34-0.84]). After adjustment, the
      use of two or three CHF drugs was associated with longer survival (HR = 0.53
      [0.36-0.77]) than the use of zero or one CHF drug. Statins were also associated
      with longer survival after adjustment (HR = 0.53 [0.31-0.89]). In patients 75
      years of age or older (n = 73), only beta-blocker treatment was associated with a
      significantly lower risk of mortality (HR = 0.31 [0.16-0.63]) in multivariate
      analysis. CONCLUSIONS: The use of beta-blockers was associated with better
      survival rates. The use of statins was also associated with better survival at 8
      years. Randomised controlled trials are required to confirm these observations.

PMID- 22993101
TI  - Neurocognitive impairment in patients randomized to second-line
      lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir
      monotherapy.
AB  - We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing
      non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination
      antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir
      monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants
      completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks
      0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV
      negative Thais. We defined NCI as performance of <-1 SD on >=2 tests. The Thai
      depression inventory was used to capture depressive symptoms. Lumbar puncture was
      optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5)
      years, and 46 % had primary school education or lower. The median CD4 count was
      196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10)
      copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline,
      20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p =
      0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 %
      (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively.
      Having NCI at baseline and lower education each predicted NCI at week 48.
      Depression scores at week 48 did not differ between arms (p = 0.47).
      Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out
      of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI
      and depression did not differ among cases failing NNRTI-based cART who received
      mLPV/r compared to LPV/r triple therapy.

PMID- 22993103
TI  - Role of VEGF/VEGFR in the pathogenesis of leukemias and as treatment targets
      (Review).
AB  - Angiogenesis plays an important role in solid tumor growth, progression and
      metastasis. Evidence suggests that the progression of hematolymphoid malignancies
      also depends on the induction of new blood vessel formation under the influence
      of acute leukemia, myelodysplastic syndromes, myeloproliferative neoplasms,
      multiple myeloma and lymphomas. The vascular endothelial growth factor (VEGF) is
      the most important proangiogenic agent that activates receptors on vascular
      endothelial cells and promotes blood vessel regeneration. It has been
      demonstrated that VEGF/VEGF receptor (VEGFR) expression is upregulated in several
      types of hematolymphoid tumor cells accompanied with angiogenesis. The levels of
      VEGF/VEGFR are correlated with the treatment, relapse and prognosis of
      hematolymphoid tumors. In order for VEGF family and their receptors as
      antiangiogenic targets to treat solid tumors, several antiangiogenic agents
      targeting VEGF-related pathways have been used for the treatment of
      hematolymphoid malignancies in clinical trials. The results demonstrate a
      promising therapeutic intervention in multiple types of hematolymphoid tumors.
      This review aims to summarize recent advances in understanding the role of VEGF
      and angiogenesis in leukemias, mainly focusing on their upstream transcriptors,
      downstream targets and the correlation of VEGF/VEGFR with the treatment, relapse
      or prognosis of leukemia. The progress of VEGF and its receptors as attractive
      targets for therapies are also discussed in clinical application.

PMID- 22993102
TI  - Coevolution of bacteria and their viruses.
AB  - Coevolution between bacteria and bacteriophages can be characterized as an
      infinitive constant evolutionary battle (phage-host arm race), which starts
      during phage adsorption and penetration into host cell, continues during phage
      replication inside the cells, and remains preserved also during prophage
      lysogeny. Bacteriophage may exist inside the bacterial cells in four forms with
      different evolutionary strategies: as a replicating virus during the lytic cycle,
      in an unstable carrier state termed pseudolysogeny, as a prophage with complete
      genome during the lysogeny, or as a defective cryptic prophage. Some defensive
      mechanisms of bacteria and virus countermeasures are characterized, and some
      evolutionary questions concerning phage-host relationship are discussed.

PMID- 22993104
TI  - Impact of the VIO system in hepatic resection for patients with hepatocellular
      carcinoma.
AB  - PURPOSES: This study aimed to evaluate a novel surgical device combination [VIO
      system containing a bipolar clamp (BiClamp) and the monopolar soft-coagulation
      (SOFT COAG)] in hepatic resection for patients with hepatocellular carcinoma
      (HCC). METHODS: This study performed 124 hepatic resections for HCC and divided
      them into 2 groups: 60 patients (Conventional group) underwent liver parenchymal
      transection using Cavitron Ultrasonic Surgical Aspirator (CUSA) system and saline
      coupled bipolar electrocautery for hemostasis; the BiClamp was used with the CUSA
      system for liver parenchymal transection and SOFT COAG was used with saline
      coupled bipolar electrocautery for hemostasis in 64 patients (VIO group).
      RESULTS: The median blood loss in the VIO group was 345 mL, which was less than
      that in the Conventional group (median 548 mL, P = 0.0423). A multivariate
      logistic regression analysis showed that no use of the VIO system (P = 0.0172)
      was an independent predictor of intraoperative blood loss, respectively. In
      patients with liver cirrhosis, the VIO group included a significantly lower
      proportion of patients with liver cirrhosis that experienced more than 500 mL of
      intraoperative blood loss in comparison to those in the Conventional group (P =
      0.0262). CONCLUSIONS: The VIO system was safe for hepatic resection and its use
      was associated with a significant decrease in intraoperative blood loss even in
      cirrhotic patients.

PMID- 22993105
TI  - Dislodged and mechanically distorted stent stuck within a previously implanted
      drug-eluting stent.
AB  - Coronary stent loss during percutaneous coronary intervention is rare and is
      often associated with significant morbidity. Several retrieval techniques,
      overlying stent deployment and crushing, and surgical removal can be used to deal
      with a stent lost in the coronary system. We successfully treated a dislodged and
      mechanically distorted coil stent stuck within a previously implanted drug
      eluting stent (DES) by stent-crush technique. This case might provide insight
      into the mechanisms responsible for the longitudinal fragility of cobalt alloy
      and coil-structure stents and stent fracture of DES. In the DES era, careful
      attention should be paid to such complications when attempting to deliver a stent
      to a distal vessel through a pre-existing DES. 

PMID- 22993106
TI  - "Estoy viejo" [I'm old]: internalized ageism as self-referential, negative,
      ageist speech in the Republic of Panama.
AB  - Ageism is a form of discrimination that anyone may experience at some point in
      life (Palmore 2004). Yet ageism is rarely the focus of behavioral research
      (Nelson 2005). Age can be understood as a social construct that reflects social
      norms (Lemus and Exposito 2005). Based on our review of the published literature,
      there were two studies on perceptions of aging among Latina/os in the United
      States (Beyene et al. 2002; Sarkisian et al. 2006). These studies investigated
      perceptions and expectations of aging among older Latina/o adults rather than
      direct experiences of ageism. It is important to note that Latina/os are not a
      homogenous group and that there are within-group differences. For this reason,
      this study explored internalized, negative ageism specifically in the Republic of
      Panama. Although Panama has unique characteristics, it also reflects Central
      American culture and therefore should provide initial insights regarding Central
      American self-referential, negative, ageist talk, which we labeled "Estoy viejo."
      Flanagan's Critical Incident Technique was used to access and understand
      participants' (ages 18-65) negative ageist talk (n=159). Participants who
      reported engaging in "Estoy viejo." (46.3% of those sampled) were significantly
      younger than participants who did not (p< .05). One potential explanation is that
      younger participants may have been more influenced by North American culture and
      its strongly negative ageist stereotypes than older participants, who may have
      identified primarily with Central American culture.

PMID- 22993107
TI  - Shrinkage in nonlinear mixed-effects population models: quantification,
      influencing factors, and impact.
AB  - Shrinkage of empirical Bayes estimates (EBEs) of posterior individual parameters
      in mixed-effects models has been shown to obscure the apparent correlations among
      random effects and relationships between random effects and covariates. Empirical
      quantification equations have been widely used for population
      pharmacokinetic/pharmacodynamic models. The objectives of this manuscript were
      (1) to compare the empirical equations with theoretically derived equations, (2)
      to investigate and confirm the influencing factor on shrinkage, and (3) to
      evaluate the impact of shrinkage on estimation errors of EBEs using Monte Carlo
      simulations. A mathematical derivation was first provided for the shrinkage in
      nonlinear mixed effects model. Using a linear mixed model, the simulation results
      demonstrated that the shrinkage estimated from the empirical equations matched
      those based on the theoretically derived equations. Simulations with a two
      compartment pharmacokinetic model verified that shrinkage has a reversed
      relationship with the relative ratio of interindividual variability to residual
      variability. Fewer numbers of observations per subject were associated with
      higher amount of shrinkage, consistent with findings from previous research. The
      influence of sampling times appeared to be larger when fewer PK samples were
      collected for each individual. As expected, sample size has very limited impact
      on shrinkage of the PK parameters of the two-compartment model. Assessment of
      estimation error suggested an average 1:1 relationship between shrinkage and
      median estimation error of EBEs.

PMID- 22993108
TI  - Characterization of maximal respiratory pressures in healthy children.
AB  - BACKGROUND: Measurements of maximal voluntary inspiratory (PI(max)) and
      expiratory (PE(max)) pressures are used in the management of respiratory muscle
      disease. There is little data on the appropriate reference range, success rates,
      or repeatability of PI(max) and PE(max) in children or on methodological factors
      affecting test outcomes. OBJECTIVES: To determine PI(max) and PE(max) in healthy
      children and examine which published reference equations are best suited to a
      contemporary population. Secondary objectives were to assess within-test
      repeatability and the influence of lung volumes on PI(max) and PE(max). METHODS:
      Healthy children were prospectively recruited from the community on a volunteer
      basis and underwent spirometry, static lung volumes, and PI(max) and PE(max)
      testing. RESULTS: Acceptable and repeatable (to within 20%) PI(max) and PE(max)
      were obtained in 156 children, with 105 (67%) children performing both PI(max)
      and PE(max) measurements to within 10% repeatability. The reference equations of
      Wilson et al. [Thorax 1984;39:535-538] best matched our healthy Caucasian
      children. There was an inverse relationship between PI(max) and the percent of
      total lung capacity (TLC) at which the measurement was obtained (beta coefficient
      -0.96; 95% CI -1.52 to -0.39; p = 0.001), whereas at lung volumes of >80% TLC
      PE(max) was independent of lung volume (p = 0.26). CONCLUSION: We demonstrated
      that the Wilson et al. [Thorax 1984;39:535-538] reference ranges are most suited
      for contemporary Caucasian Australasian children. However, robust multiethnic
      reference equations for maximal respiratory pressures are required. This study
      suggests that 10% within-test repeatability criteria are feasible in clinical
      practice, and that the use of lung volume measurements will improve the quality
      of maximal respiratory pressure measurements.

PMID- 22993109
TI  - Current strategies in treating severe contact dermatitis in pediatric patients.
AB  - Allergic contact dermatitis in children is underdiagnosed and undertreated, and
      its incidence is increasing. Appropriate history taking and the suspicion for
      allergic contact dermatitis is essential, and patch testing remains the gold
      standard in diagnosis. Avoidance of the offending allergen, once identified, is
      the first goal of treatment. Medical therapies include topical corticosteroid and
      topical immunomodulators. In severe cases, oral corticosteroids or
      immunomodulators are utilized, although prospective randomized trials for the
      treatment of this disease in children are lacking. A PubMed literature search was
      performed to identify publications on allergic contact dermatitis in the
      pediatric population with the keywords: dermatitis, children, allergic contact
      dermatitis, pediatrics, contact hypersensitivity, contact allergy, treatment, and
      management. This review will address the major principles behind the diagnosis
      and management of this disease in the pediatric population, and highlight useful
      strategies that may result in improved treatment of this condition.

PMID- 22993111
TI  - Laparoscopic gastrectomy after incomplete endoscopic resection for early gastric
      cancer.
AB  - Endoscopic submucosal dissection (ESD) utilizes electrical coagulation, which can
      cause burns, fibrosis and adhesion of the stomach and surrounding tissue; these
      complications might increase the surgical difficulties for subsequent laparoscopy
      assisted gastrectomy (LAG) and the risk of complications. However, scarce data
      are available on the influence of previous ESD on LAG. The purpose of this study
      was to evaluate the feasibility and safety of LAG following incomplete ESD in
      patients with early gastric cancer. Ninety-seven patients who underwent LAG were
      analyzed retrospectively; 17 patients had undergone ESD previously and the
      remaining 80 patients had no history of ESD. Clinicopathological data and
      surgical outcomes were compared between the two groups. No differences were
      observed in surgical outcomes of LAG after ESD in terms of operation time,
      intraoperative blood loss, total number of harvested lymph nodes, time until
      start of flatus, and postoperative hospital stay. These results were not
      influenced by tumor location and operative procedures. In conclusion, in terms of
      surgical outcomes, LAG is a safe and feasible procedure for the treatment of
      early gastric cancer regardless of previous endoscopic treatment. LAG may be the
      first-choice radical treatment after incomplete ESD for early gastric cancer.

PMID- 22993110
TI  - A novel method for RNA extraction from Andosols using casein and its application
      to amoA gene expression study in soil.
AB  - The lack of a universal method to extract RNA from soil hinders the progress of
      studies related to nitrification in soil, which is an important step in the
      nitrogen cycle. It is particularly difficult to extract RNA from certain types of
      soils such as Andosols (volcanic ash soils), which is the dominant agricultural
      soil in Japan, because of RNA adsorption by soil. To obtain RNA from these
      challenging soils to study the bacteria involved in nitrification, we developed a
      soil RNA extraction method for gene expression analysis. Autoclaved casein was
      added to an RNA extraction buffer to recover RNA from soil, and high-quality RNA
      was successfully extracted from eight types of agricultural soils that were
      significantly different in their physicochemical characteristics. To detect
      bacterial ammonia monooxygenase subunit A gene (amoA) transcripts, bacterial
      genomic DNA and messenger RNA were co-extracted from two different types of
      Andosols during incubation with ammonium sulfate. Polymerase chain reaction
      denaturing gradient gel electrophoresis and reverse transcription polymerase
      chain reaction-denaturing gradient gel electrophoresis analyses of amoA in soil
      microcosms revealed that only few amoA, which had the highest similarities to
      those in Nitrosospira multiformis, were expressed in these soils after treatment
      with ammonium sulfate, although multiple amoA genes were present in the soil
      microcosms examined.

PMID- 22993112
TI  - Color stability of siloranes versus methacrylate-based composites after immersion
      in staining solutions.
AB  - OBJECTIVES: The purpose of this study was to determine, by using a
      spectrophotometer device, the color stability of silorane in comparison with four
      methacrylate-based composites after being immersed in different staining
      solutions such as coffee, black tea, red wine, orange juice, and coke, and
      distilled water as control group. METHODS: Four restorative methacrylate-based
      composites (Filtek Z250, TetricEvoCeram, Venus Diamond, and Grandio) and one
      silorane (FiltekSilorane) of shade A2 were selected to measure their color
      stability (180 disk samples) after 4 weeks of immersion in six staining
      solutions: black tea, coffee, red wine, orange juice, coke, and distilled water.
      The specimen's color was measured each week by means of a spectrophotometer (CIE
      L*a*b* system). Statistical analysis was carried out performing an ANOVA and LSD
      Test in order to statistically analyze differences in L*a*b*and ?E values.
      RESULTS: All materials showed significant discoloration (p < 0.05) when compared
      to the control group (immersed in distilled water). The Highest ?E observed was
      with red wine, whereas coke led to the lowest one. Silorane showed the highest
      color stability compared with methacrylate-based composites. CONCLUSIONS:
      Methacrylate-based materials immersed in staining solutions showed lower color
      stability when compared with silorane. Great differences in ?E were found among
      the methacrylate-based materials tested. CLINICAL RELEVANCE: Although color
      stability of methacrylate-based composites immersed in staining solutions has
      been widely investigated, this has not been done for long immersion periods with
      silorane-based composites.

PMID- 22993113
TI  - Three-rooted premolar analyzed by high-resolution and cone beam CT.
AB  - OBJECTIVES: The aim of this study was to analyze the variations in canal and root
      cross-sectional area in three-rooted maxillary premolars between high-resolution
      computed tomography (MUCT) and cone beam computed tomography (CBCT). MATERIALS
      AND METHODS: Sixteen extracted maxillary premolars with three distinct roots and
      fully formed apices were scanned using MUCT and CBCT. Photoshop CS software was
      used to measure root and canal cross-sectional areas at the most cervical and the
      most apical points of each root third in images obtained using the two
      tomographic computed (CT) techniques, and at 30 root sections equidistant from
      both root ends using MUCT images. Canal and root areas were compared between each
      method using the Student t test for paired samples and 95 % confidence intervals.
      RESULTS: Images using MUCT were sharper than those obtained using CBCT. There
      were statistically significant differences in mean area measurements of roots and
      canals between the MUCT and CBCT techniques (P < 0.05). Root and canal areas had
      similar variations in cross-sectional MUCT images and became proportionally
      smaller in a cervical to apical direction as the cementodentinal junction was
      approached, from where the area then increased apically. CONCLUSION: Although
      variation was similar in the roots and canals under study, CBCT produced poorer
      image details than MUCT. CLINICAL RELEVANCE: Although CBCT is a strong diagnosis
      tool, it still needs improvement to provide accuracy in details of the root canal
      system, especially in cases with anatomical variations, such as the three-rooted
      maxillary premolars.

PMID- 22993114
TI  - Anatomically plausible illusory posture affects mental rotation of body parts.
AB  - During mental rotation (MR) of body parts, people internally simulate the
      movement of their corresponding body segments. These sensory-motor mechanisms
      render MR sensitive to proprioceptive information (e.g., posture). Similar
      mechanisms can alter illusory hand ownership following synchronous visuotactile
      stimulation (e.g., the rubber hand illusion [RHI]). In the present study, we
      first showed that illusory ownership for a fake hand can also be induced when the
      posture of the fake hand (palm-up) does not correspond with the subject's
      physical hand posture (palm-down). Then we tested whether illusory ownership for
      a fake hand in such a posture impacts the MR of hands carried out immediately and
      repeatedly after the RHI. The results showed that MR was altered for the view
      corresponding to the fake hand's posture, but not for other views. Additionally,
      these effects depended on illusory ownership, as only synchronous visuotactile
      stimulation was found to lead to these changes, characterized by a modulation of
      the rotation-dependent profile of MR response times. These findings show that
      similar sensory-motor mechanisms are recruited during the MR of hands and
      illusory hand ownership manipulated through multisensory mismatch, and that
      bottom-up visuotactile stimulation interferes with high-level imagery processes.

PMID- 22993115
TI  - The molecular autopsy: an indispensable step following sudden cardiac death in
      the young?
AB  - Annually thousands of sudden deaths involving young individuals (<35 years of
      age) remain unexplained following a complete medicolegal investigation that
      includes an autopsy. In fact, epidemiological studies have estimated that over
      half of sudden deaths involving previously healthy young individuals have no
      morphological abnormalities identifiable at autopsy. Cardiac channelopathies
      associated with structurally normal hearts such as long QT syndrome (LQTS),
      catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada
      syndrome (BrS), leave no evidence to be found at autopsy, leaving investigators
      to only speculate that a lethal arrhythmia might lie at the heart of a sudden
      unexplained death (SUD). In cases of autopsy-negative SUD, continued
      investigation, through the use of a cardiological and genetic evaluation of first
      or second-degree relatives and/or a molecular autopsy, may pinpoint the
      underlying mechanism attributing to the sudden death and allow for the
      identification of living family members with the pathogenic substrate that
      renders them vulnerable to an increased risk for cardiac events, including sudden
      death.

PMID- 22993116
TI  - Sudden cardiac death in the young: how can disease recognition and prevention in
      family members be improved?
AB  - Sudden cardiac death (SCD) in young patients (<45 years of age) is a rare event.
      However, it is particularly tragic as it affects active and often otherwise
      healthy individuals. Furthermore, SCD may unmask an underlying congenital
      structural disease or channelopathy. The leading cause of SCD is coronary artery
      disease; however, the likelihood of an underlying congenital cardiac disease is
      higher in young individuals. Each SCD should therefore initiate a thorough work
      up of an underlying cardiac cause, which should ideally include a molecular
      autopsy. Familial screening should also be initiated if a physician is years
      later confronted with a history of SCD in a young patient. The common aim is to
      prompt identification of affected family members, to include the patient in
      regular cardiological follow-up and if indicated to initiate prophylactic therapy
      to prevent further SCD. This current issue on hereditary cardio(myo)pathy will
      cover the main topics on familial diseases. In addition the role of molecular
      autopsy and molecular genetic screening is discussed.

PMID- 22993117
TI  - [Genetic testing in hereditary arrythmia syndromes today and in the future].
AB  - Genetic testing already has a substantial impact in identifying hereditary
      arrhythmia syndromes after sudden death in young patients. This report provides
      information on current developments, available options and reasonable approaches
      in the clinical setting. In addition the limitations of genetic testing are
      discussed. Genetic testing is only useful for patients in the context of clinical
      findings interpreted by an experienced cardiogenetics team.

PMID- 22993118
TI  - [Brugada syndrome].
AB  - Brugada syndrome is a rare, hereditary and primary electrical disease which is
      associated with a risk of syncope and sudden cardiac death. Initially, Brugada
      syndrome was considered to be a very malignant disease; however, in subsequent
      studies the risk of sudden death especially in asymptomatic patients was much
      lower than initially expected. In patients with Brugada type 1 electrocardiogram
      (ECG) findings and rhythmogenic syncope or sudden cardiac arrest, implantable
      cardioverter-defibrillator (ICD) implantation is indicated. Risk stratification
      and therapy in asymptomatic patients is controversially discussed and is
      clinically challenging. Due to the low event rate in asymptomatic patients with
      Brugada syndrome the identification of predictors of sudden cardiac death is
      difficult. Thus, risk stratification and therapy in asymptomatic patients has to
      be performed individually. This manuscript reviews the current data on diagnosis,
      risk stratification and therapy of Brugada syndrome.

PMID- 22993119
TI  - Study on the selectivity of anion receptors based on similar (thio)urea
      fragments.
AB  - Three new selective anion receptors containing the (thio)urea binding sites were
      developed, Indole-3-formaldehyde phenyl-semithiocarbazone, Indole-3-formaldehyde
      nitrophenyl-semithiocarbazone, and Indole-3-formaldehyde nitrophenyl
      semicarbazone, nominated as receptors 1, 2 and 3, respectively. Receptor 1 shows
      high selective recognition for F(-) only, while both receptor 2 and receptor 3
      containing a p-nitro group show high selective recognition for AcO(-). The high
      selective recognition of these receptors to anions is further investigated by X
      ray crystallography diffraction, UV-vis, fluorescence analyses and (1)H NMR.
      Furthermore, receptor 2 changes from yellow to orange, and receptor 3 darkens
      when acetate is added, providing a way of detection by 'naked-eye'.

PMID- 22993120
TI  - On the photophysicochemical properties of selected fluoroquinolones:
      solvatochromic and fluorescence spectroscopy study.
AB  - The photophysicochemical properties of selected fluoroquinolones in different
      solvents of various physical properties, including polarity and hydrogen bonding
      ability, were investigated using steady state fluorescence spectroscopy. The
      solvent-dependant fluorescence emission spectra of selected fluoroquinolones,
      namely ciprofloxacin (CIPR) and enrofloxacin (ENRO), were employed to gain
      insights concerning its photophysicochemical properties of interests.
      Interestingly, fluorescence spectra of the selected drugs exhibited structured
      emission spectra in nonpolar solvents such as hexane, whereas unstructured
      spectra were observed in more polar solvents such as alcohols and water. Also, a
      notable bathochromic shift in lambda(max)(em) was observed in fluorescence
      spectra of both drugs with increasing solvent polarity that resulted in biphasic
      behavior upon applying the Lippert-Mataga correlation that correspond to general
      and specific solvent effects. Applying the Lippert-Mataga correlation to the
      fluorescence spectra of CIPR and ENRO in various solvents was employed to
      estimate the dipole moment difference between the ground and excited states of
      them, DeltaMU(MU(e) - MU(g)), where obtained results revealed the values of 9.4
      and 16.2 Debye for the LE and ICT states of ENRO, respectively, and 8.0 and 16.2
      Debye for the LE and ICT states of CIPR, respectively. Multiple linear regression
      analysis (MLRA) based on Kamlet-Taft equating was applied against absorption
      frequency (nu(abs)), emission frequency (nu(em)), Stokes shift (?nu), and
      fluorescence quantum yield (Phi(f)), where obtained results revealed excellent
      correlation (R: 0.916-0.966) that are consistent with other results considering
      the effect of solvent polarizability, hydrogen bonding ability, and viscosity on
      the photophysicochemical properties of the studied fluoroquinolones.

PMID- 22993121
TI  - Formation and characterization of stable fluorescent complexes between neutral
      conjugated polymers and cyclodextrins.
AB  - Solubilisation and stabilization of conjugated polymers, CPs, in aqueous media
      remains a challenge for many researches trying to extend the biological and
      environmental applications of this kind of polymers. A number of different
      alternatives have been considered to address this problem, which are mostly based
      on the enhancement of the macromolecule polarity, by appending hydrophilic side
      chains on the polymer backbone. In this work we have investigated a new strategy
      in which water solubilization is reached by external addition of classical
      cyclodextrins (alpha-, beta- and gamma-CDs) to a solution of non-polar CPs. This
      strategy allows working with such polymers eliminating the need to synthesize new
      water-soluble species. The polymer selected for the study was poly-[9,9-bis(6'
      bromohexyl-2,7-fluoren-dyil)-co-alt-(benzene-1,4-diy)], PFPBr(2), a polyfluorene
      previously synthesized in our laboratory. Results show that PFPBr(2) forms
      fluorescent complexes in aqueous media with beta-CD and gamma-CD, and much less
      efficiently with alpha-CD, probably due to the small size of its cavity. The new
      PFPBr(2)/CD complexes are stable in time and in a large range of pH, however, at
      high concentration and temperature, they tend to aggregate and precipitate. In
      order to increase stabilization and minimize polymer aggregation, complexes were
      encapsulated inside the pores of silica glasses fabricated using the sol-gel
      process, obtaining transparent and fluorescent hybrid matrices which were stable
      in time and temperature. In addition, immobilization of the complexes allows an
      easy manipulation of the material, thus offering promising applications in the
      development of biological and chemical sensors.

PMID- 22993122
TI  - Quality by design I: Application of failure mode effect analysis (FMEA) and
      Plackett-Burman design of experiments in the identification of "main factors" in
      the formulation and process design space for roller-compacted ciprofloxacin
      hydrochloride immediate-release tablets.
AB  - As outlined in the ICH Q8(R2) guidance, identifying the critical quality
      attributes (CQA) is a crucial part of dosage form development; however, the
      number of possible formulation and processing factors that could influence the
      manufacturing of a pharmaceutical dosage form is enormous obviating formal study
      of all possible parameters and their interactions. Thus, the objective of this
      study is to examine how quality risk management can be used to prioritize the
      number of experiments needed to identify the CQA, while still maintaining an
      acceptable product risk profile. To conduct the study, immediate-release
      ciprofloxacin tablets manufactured via roller compaction were used as a prototype
      system. Granules were manufactured using an Alexanderwerk WP120 roller compactor
      and tablets were compressed on a Stokes B2 tablet press. In the early stages of
      development, prior knowledge was systematically incorporated into the risk
      assessment using failure mode and effect analysis (FMEA). The factors identified
      using FMEA were then followed by a quantitative assessed using a Plackett-Burman
      screening design. Results show that by using prior experience, literature data,
      and preformulation data the number of experiments could be reduced to an
      acceptable level, and the use of FMEA and screening designs such as the Plackett
      Burman can rationally guide the process of reducing the number experiments to a
      manageable level.

PMID- 22993123
TI  - The effects of supercritical carbon dioxide processing on progesterone dispersion
      systems: a multivariate study.
AB  - The aim of this work was to investigate the effects of supercritical carbon
      dioxide (SC-CO(2)) processing on the release profiles of progesterone (PGN) and
      Gelucire 44/14 dispersion systems. A fractional factorial design was conducted
      for optimization of the particles from gas-saturated suspension (PGSS) method and
      formulation parameters and evaluating the effects of three independent responses:
      PGSS process yield, in vitro dissolution extent after 20 min (E(20)) and t (1/2)
      for prepared PGN dispersion systems. The experimental domain included seven
      factors measured at two levels to determine which factors represent the greatest
      amount of variation, hence the most influence on the resulting PGN dispersion
      systems. Variables tested were temperature (A) and pressure (B) of the
      supercritical fluid, sample loading (C), SC-CO(2) processing time (D), sonication
      (E), drug-to-excipient ratio (F) and orifice diameter into the expansion chamber
      (G). The analysis of variance showed that the factors tested had significant
      effects on the responses (p value <0.05). It was found that the optimum values of
      the PGSS process are higher pressure (186 bar), higher temperature (60 degrees
      C), a longer processing time (30 min) and lower PGN-to-excipient ratio of 1:10.
      The corresponding processing yield was 94.7%, extent of PGN dissolution after 20
      min was 85.6% and the t (1/2) was 17.7 min. The results suggest that Gelucire
      44/14-based dispersion systems might represent a promising formulation for
      delivery of PGN. The preparation of PGN-loaded Gelucire 44/14 dispersion systems
      from a PGSS method can be optimized by factorial design experimentation.

PMID- 22993124
TI  - Genetics of type 2 diabetes in East Asian populations.
AB  - Because type 2 diabetes (T2D) is highly familial, there has been a concentrated
      effort to uncover the genetic basis of T2D worldwide over the last decade. In
      East Asians, T2D is experiencing a rapidly rising prevalence that is
      characterized by a relatively lower body mass index, as compared with that in
      Europeans. To date, at least 15 convincing T2D loci have been identified from
      large-scale genome-wide association studies and meta-analyses in East Asians.
      Many of these are likely responsible for pancreatic beta cell function, as
      indicated in studies from Europeans. Many T2D loci have been replicated across
      the ethnic groups. There are, however, substantial interethnic differences in
      frequency and effect size of these risk alleles. Despite accumulating genetic
      information on T2D, there are still limitations in our ability to explain the
      rapidly rising prevalence and lean phenotype of disease observed in East Asians,
      suggesting that more extensive work using diverse research strategies is needed
      in the future.

PMID- 22993125
TI  - The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in
      amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with
      TDP-43 inclusions (FTLD-TDP) patients.
AB  - RNA-binding protein pathology now represents one of the best characterized
      pathologic features of amyotrophic lateral sclerosis (ALS) and frontotemporal
      lobar degeneration patients with TDP-43 or FUS pathology (FTLD-TDP and FTLD-FUS).
      Using liquid chromatography tandem mass spectrometry, we identified altered
      levels of the RNA-binding motif 45 (RBM45) protein in the cerebrospinal fluid
      (CSF) of ALS patients. This protein contains sequence similarities to TAR DNA
      binding protein 43 (TDP-43) and fused-in-sarcoma (FUS) that are contained in
      cytoplasmic inclusions of ALS and FTLD-TDP or FTLD-FUS patients. To further
      characterize RBM45, we first verified the presence of RBM45 in CSF and spinal
      cord tissue extracts of ALS patients by immunoblot. We next used
      immunohistochemistry to examine the subcellular distribution of RBM45 and
      observed in a punctate staining pattern within nuclei of neurons and glia in the
      brain and spinal cord. We also detected RBM45 cytoplasmic inclusions in 91 % of
      ALS, 100 % of FTLD-TDP and 75 % of Alzheimer's disease (AD) cases. The most
      extensive RBM45 pathology was observed in patients that harbor the C9ORF72
      hexanucleotide repeat expansion. These RBM45 inclusions were observed in spinal
      cord motor neurons, glia and neurons of the dentate gyrus. By confocal
      microscopy, RBM45 co-localizes with ubiquitin and TDP-43 in inclusion bodies. In
      neurons containing RBM45 cytoplasmic inclusions we often detected the protein in
      a punctate pattern within the nucleus that lacked either TDP-43 or ubiquitin. We
      identified RBM45 using a proteomic screen of CSF from ALS and control subjects
      for candidate biomarkers, and link this RNA-binding protein to inclusion
      pathology in ALS, FTLD-TDP and AD.

PMID- 22993126
TI  - Amyloid plaque formation precedes dendritic spine loss.
AB  - Amyloid-beta plaque deposition represents a major neuropathological hallmark of
      Alzheimer's disease. While numerous studies have described dendritic spine loss
      in proximity to plaques, much less is known about the kinetics of these
      processes. In particular, the question as to whether synapse loss precedes or
      follows plaque formation remains unanswered. To address this question, and to
      learn more about the underlying kinetics, we simultaneously imaged amyloid plaque
      deposition and dendritic spine loss by applying two-photon in vivo microscopy
      through a cranial window in double transgenic APPPS1 mice. As a result, we first
      observed that the rate of dendritic spine loss in proximity to plaques is the
      same in both young and aged animals. However, plaque size only increased
      significantly in the young cohort, indicating that spine loss persists even many
      months after initial plaque appearance. Tracking the fate of individual spines
      revealed that net spine loss is caused by increased spine elimination, with the
      rate of spine formation remaining constant. Imaging of dendritic spines before
      and during plaque formation demonstrated that spine loss around plaques commences
      at least 4 weeks after initial plaque formation. In conclusion, spine loss
      occurs, shortly but with a significant time delay, after the birth of new
      plaques, and persists in the vicinity of amyloid plaques over many months. These
      findings hence give further hope to the possibility that there is a therapeutic
      window between initial amyloid plaque deposition and the onset of structural
      damage at spines.

PMID- 22993128
TI  - Humanness beliefs about behavior: an index and comparative human-nonhuman
      behavior judgments.
AB  - Social psychological research suggests that two distinct dimensions describe lay
      conceptions of humanness: a species-typical sense (i.e., human nature) and a
      species-unique sense (i.e., human uniqueness). Although these two senses of
      humanness have been discerned among psychological traits and states, there has
      been no systematic research into lay beliefs about the humanness of human
      behaviors. Using a range of 60 prosocial, nonsocial, and antisocial behaviors, it
      was demonstrated that people discriminate between species-typical and species
      unique behaviors and that the capacity to perform species-unique behaviors
      distinguishes humans from animals, whereas the capacity to perform species
      typical behaviors distinguishes humans from robots. Behaviors that exemplify the
      two senses of humanness are identified, and data representing rankings, raw
      scores, and z-scores in two indices of species typicality and species uniqueness
      are provided. Taken together, these findings expand our understanding of lay
      conceptions of humanness and provide researchers of humanness with a wider range
      of validated stimuli to probe the boundaries of humanity.

PMID- 22993127
TI  - No evidence for the effectiveness of systemic corticosteroids in acute
      pharyngitis, community-acquired pneumonia and acute otitis media.
AB  - Corticosteroids have been used to treat infectious diseases for more than 50
      years but, although it has been shown that they are highly effective in improving
      the clinical course of some diseases, their effects have not been clearly defined
      in others. Nevertheless, they are still used by a considerable number of
      physicians. This review analyses the role of systemic corticosteroids in the
      treatment of acute pharyngitis (AP), community-acquired pneumonia (CAP) and acute
      otitis media (AOM). A number of trials involving patients with AP have been
      carried out, but most are marred by methodological flaws that do not allow any
      firm conclusions to be drawn. The number of trials involving CAP patients is even
      higher, and the data suggest that corticosteroids may reduce the risk of death
      only in patients with severe disease. There are very few data concerning AOM, and
      there is currently no reason for prescribing corticosteroids to treat it.
      Overall, the data showed that there is, currently, no indication for the
      universal use of systemic corticosteroids in any of the reviewed diseases and,
      further, high-quality studies of all of these respiratory tract infections are
      needed in order to identify the patients for whom the prescription of
      corticosteroids is rationally acceptable.

PMID- 22993130
TI  - Where science meets practice.

PMID- 22993131
TI  - Review of material recovery from used electric and electronic equipment
      alternative options for resource conservation.
AB  - For waste from electric and electronic equipment, the WEEE Directive stipulates
      the separate collection of electric and electronic waste. As to new electric and
      electronic devices, the Restriction of Hazardous Substances (RoHS) Directive bans
      the use of certain chemicals dangerous for man and environment. From the
      implementation of the WEEE directive, many unsolved problems have been
      documented: poor collection success, emission of dangerous substances during
      collection and recycling, irretrievable loss of valuable metals among others. As
      to RoHS, data from the literature show a satisfying success. The problems
      identified in the process can be reduced to some basic dilemmas at the borders
      between waste management, product policy and chemical safety. The objectives of
      the WEEE Directive and the specific targets for use and recycling of appliances
      are not consistent. There is no focus on scarce resources. Extended producer
      responsibility is not sufficient to guarantee sustainable waste management. Waste
      management reaches its limits due to problems of implementation but also due to
      physical laws. A holistic approach is necessary looking at all branch points and
      sinks in the stream of used products and waste from electric and electronic
      equipment. This may be done with respect to the general rules for sustainable
      management of material streams covering the three dimensions of sustainable
      policy. The relationships between the players in the field of electric and
      electronic devices have to be taken into account. Most of the problems identified
      in the implementation process will not be solved by the current amendment of the
      WEEE Directive.

PMID- 22993132
TI  - Business waste prevention: a review of the evidence.
AB  - Waste prevention is a policy priority in many countries. For example, European
      Union member states are currently required to prepare a national Waste Prevention
      Programme. This article reports on a major international review of the evidence
      base for business waste prevention to underpin such policy-making. A strict
      definition of waste prevention is used, including waste avoidance, waste
      reduction at source or in process, and product reuse-recycling is outside the
      scope of this article. The review was organised with two key dimensions. Eight
      types of policy intervention were identified: standards, labelling, procurement,
      commitments and voluntary agreements, communication, incentives, waste
      minimisation clubs and other business support. Six illustrative sectors were
      selected: construction and demolition, food and drink, hospitality, retail,
      automotive and office-based services. Four broad approaches to business waste
      prevention have been distinguished and used as part of the analytical framework,
      classified into a two by two matrix, using supply- and demand-side drivers as one
      axis, and incremental versus radical change as the other. A fundamental focus was
      on attitudes and behaviours. A conceptual framework is presented to navigate the
      various behavioural influences on businesses, and to discuss those motivations
      and barriers for which the evidence is relatively robust. The results suggest
      that the (financial) benefits to business of waste prevention are potentially
      huge, and that some progress is being made, but measurement is a challenge. A
      taster of some of the learnings on the effectiveness of the different policy
      interventions to promote waste prevention is also presented.

PMID- 22993129
TI  - Omega-3 polyunsaturated fatty acids reduce vascular endothelial growth factor
      production and suppress endothelial wound repair.
AB  - Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFAs) such as
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have diverse
      beneficial effects on cardiovascular diseases and have been used widely as
      supplements in reducing the risk of cardiovascular diseases. The beneficial
      effects are believed to be related to the anti-inflammatory and antioxidant
      action of n-3 PUFA. EPA and DHA can inhibit inflammatory cytokine-induced
      endothelial activation and reduce endothelial migration and proliferation.
      Revascularisation is the major therapeutic approach for end-stage cardiovascular
      diseases, and endothelial migration and proliferation are essential for the
      success of revascularisation. The aim of this study was to investigate the role
      of n-3 PUFAs on vascular endothelial wound repair. A scratch-wound repair assay
      was carried out in cultured human microvascular endothelial cells (HMEC-1) with
      and without different concentrations of DHA or EPA. The effect of DHA and EPA on
      HMEC-1 proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The effect of DHA and EPA on vegf mRNA
      expression was detected by real-time RT-PCR and vascular endothelial growth
      factor (VEGF) protein secretion by enzyme-linked immunosorbent assay. DHA and EPA
      dose-dependently suppressed HMEC-1 cell proliferation and wound repair. DHA and
      EPA treatment did not induce significant HMEC-1 cell death. The treatment,
      however, significantly suppressed vegf mRNA expression and protein secretion in
      both normoxia and hypoxia culture conditions. The addition of exogenous VEGF
      prevented DHA- and EPA-mediated suppression of HMEC-1 cell proliferation. DHA and
      EPA have anti-angiogenic effect partially through vegf suppression. The use of
      DHA and EPA may benefit angiogenic diseases, but may have potential side effects
      to patients undergoing revascularisation therapy. Further studies will be
      required to confirm the effect of n-3 PUFAs on vascular repair.

PMID- 22993133
TI  - National waste prevention programs: indicators on progress and barriers.
AB  - Defining the prevention of waste as top priority of the waste hierarchy--as
      confirmed by the revised Waste Framework Directive (WFD)--is much more than a
      simple amendment of ways to deal with waste, but means nothing less than a
      fundamental change of the socio-technical system of waste infrastructures and
      requires a transition from end-of-pipe technologies towards an integrated
      management of resources. The WFD therefore obligates member states to develop
      national waste prevention programs as a new policy instrument with the
      development of waste prevention indicators as one of the core elements. The
      article discusses the limitations of waste-based key figures and shows the need
      for more process-oriented indicators. As part of the development of national
      waste prevention programs such indicators reveal the relevance of different
      barriers that have to be overcome in order to make prevention an effective top
      priority in the waste hierarchy. With regard to path dependencies caused by sunk
      costs in end-of-pipe waste infrastructures the absolute amount of integrated
      environmental investments, as well as their share of the total waste-related
      investments, can be seen as indicators for the level of innovation activities
      aimed at waste prevention. Sector-specific indicators for the production phase
      could be used as benchmarks and to highlight differences in the need for policy
      interventions.

PMID- 22993134
TI  - Extended producer responsibility for consumer waste: the gap between economic
      theory and implementation.
AB  - Although economic theory supports the use of extended producer responsibility
      (EPR) to stimulate prevention and recycling of waste, EPR systems implemented in
      Europe are often criticized as a result of weak incentives for prevention and
      green product design. Using a stylized economic model, this article evaluates the
      efficiency of European EPR systems. The model reveals that the introduction of
      static collection targets creates a gap between theory and implementation. Static
      targets lead to inefficient market outcomes and weak incentives for prevention
      and green product design. The minimum collection targets should be complemented
      with a tax on producers for the non-collected waste fraction. Because such a tax
      internalizes the cost of waste disposal, more efficient price signals will lead
      to better incentives for waste management in a complex and dynamic market.

PMID- 22993135
TI  - An analytical framework and tool ('InteRa') for integrating the informal
      recycling sector in waste and resource management systems in developing
      countries.
AB  - In low- and middle-income developing countries, the informal (collection and)
      recycling sector (here abbreviated IRS) is an important, but often unrecognised,
      part of a city's solid waste and resources management system. Recent evidence
      shows recycling rates of 20-30% achieved by IRS systems, reducing collection and
      disposal costs. They play a vital role in the value chain by reprocessing waste
      into secondary raw materials, providing a livelihood to around 0.5% of urban
      populations. However, persisting factual and perceived problems are associated
      with IRS (waste-picking): occupational and public health and safety (H&S), child
      labour, uncontrolled pollution, untaxed activities, crime and political
      collusion. Increasingly, incorporating IRS as a legitimate stakeholder and
      functional part of solid waste management (SWM) is attempted, further building
      recycling rates in an affordable way while also addressing the negatives. Based
      on a literature review and a practitioner's workshop, here we develop a
      systematic framework--or typology--for classifying and analysing possible
      interventions to promote the integration of IRS in a city's SWM system. Three
      primary interfaces are identified: between the IRS and the SWM system, the
      materials and value chain, and society as a whole; underlain by a fourth, which
      is focused on organisation and empowerment. To maximise the potential for
      success, IRS integration/inclusion/formalisation initiatives should consider all
      four categories in a balanced way and pay increased attention to their
      interdependencies, which are central to success, including specific actions, such
      as the IRS having access to source separated waste. A novel rapid evaluation and
      visualisation tool is presented--integration radar (diagram) or InterRa--aimed at
      illustrating the degree to which a planned or existing intervention considers
      each of the four categories. The tool is further demonstrated by application to
      10 cases around the world, including a step-by-step guide.

PMID- 22993136
TI  - New developments in waste management in the Netherlands.
AB  - With a current recycling rate of 51% the Netherlands has one of the leading
      positions in the recycling of household waste in Europe. However, in the last 10
      15 years there have been few developments made in the recycling of household
      waste. The introduction of producer responsibility for waste electrical and
      electronic equipment in 1999 and for packaging in 2005 have been the biggest
      changes in this period. However, these measures have, so far, not significantly
      influenced the overall recycling rate for household waste. In order to plan the
      next steps, which are necessary to reach the goals of the National Waste
      Management plan, new innovative methods are needed. A number of Dutch
      municipalities and waste collection companies are investigating promising new
      paths to enhance separate collection and recycling of household waste. This
      article reports on three of the most interesting initiatives.

PMID- 22993137
TI  - The implementation of anaerobic digestion of food waste in a highly populated
      urban area: an LCA evaluation.
AB  - While source separation of waste packaging materials for recycling is well
      established in several metropolitan areas, the collection of food waste from the
      households is less widespread because of its more difficult implementation.
      Source segregation of food waste in densely populated areas is raising new
      interest, as the availability of biogas following its anaerobic digestion (AD)
      paves the road to a number of possibilities, from electric energy production to
      its upgrading to biomethane and subsequent feeding in to the natural gas network
      or in vehicles as a fuel. The study addresses this waste management option by
      analysing a real metropolitan situation where food waste currently ends up mixed
      with the residual waste in a waste-to-energy plant (WTE). We assume to establish
      a new collection scheme for household food waste, followed by its treatment in a
      new AD and post-composting facility. A comparative life cycle assessment was
      carried out, where possible synergies between the existing WTE plant and the new
      one were evaluated. All new scenarios based on AD attained similar or better
      results compared with the reference scenario for almost all of the impact
      indicators. The most robust indication is related to global warming potential,
      with a potential improvement of up to 37%. Finally, a sensitivity analysis was
      carried out to assess the effect of the variation of the most relevant
      parameters. Results have proven to be very sensible to the hypothesis on the type
      of substituted electric energy. All the other examined sensitivities resulted in
      variations well below 10%.

PMID- 22993138
TI  - Site-specific criteria for the completion of landfill aftercare.
AB  - Municipal solid waste (MSW) landfills need to be managed after closure to assure
      long-term environmental compatibility. Aftercare can be completed when the
      authorities consider the landfill not likely to pose a threat to humans and the
      environment. In this work, a methodology for deriving site-specific aftercare
      completion criteria is presented and its application is illustrated via a case
      study. The evaluation method combines models addressing waste emission behavior,
      long-term barrier performance, and pollutant migration to assess the potential
      impact of landfill emissions on the environment. Based on the definition of
      acceptable impact levels at certain points of compliance, scenario- and pollutant
      specific aftercare completion criteria are derived. The methodology was applied
      to a closed MSW landfill in Austria and potential aftercare durations were
      determined. While landfill gas emissions may become environmentally tolerable
      within decades at the site, leachate-related aftercare measures were expected to
      be necessary for centuries (primarily as a result of ammonium). Although the
      evaluation comes with large uncertainties, it allows for linking aftercare
      intensity and duration with respect to an environmentally compatible state of the
      landfill in the absence of aftercare. However, further case studies including
      regulatory review and acceptance are needed to use the methodology in a decision
      support tool on aftercare completion.

PMID- 22993139
TI  - Management of healthcare waste: developments in Southeast Asia in the twenty
      first century.
AB  - In many Southeast Asian countries, significant challenges persist with regard to
      the proper management and disposal of healthcare waste. The amount of healthcare
      waste in these countries is continuously increasing as a result of the expansion
      of healthcare systems and services. In the past, healthcare waste, if it was
      treated at all, was mainly incinerated. In the last decade more comprehensive
      waste management systems were developed for Southeast Asian countries and
      implementation started. This also included the establishment of alternative
      healthcare waste treatment systems. The developments in the lower-middle-income
      countries are of special interest, as major investments are planned. Based upon
      sample projects, a short overview of the current development trends in the
      healthcare waste sector in Laos, Indonesia and Vietnam is provided. The projects
      presented include: (i) Lao Peoples Democratic Republic (development of the
      national environmental health training system to support the introduction of
      environmental health standards and improvement of healthcare waste treatment in
      seven main hospitals by introducing steam-based treatment technologies); (ii)
      Indonesia (development of a provincial-level healthcare waste-management strategy
      for Province Nanggroe Aceh Darussalam (NAD) and introduction of an advanced waste
      treatment system in a tertiary level hospital in Makassar); and (iii) Vietnam
      (development of a healthcare waste strategy for five provinces in Vietnam and a
      World Bank-financed project on healthcare waste in Vietnam).

PMID- 22993140
TI  - Approach to the diagnosis and management of retained rectal foreign bodies:
      clinical update.
AB  - Retained rectal foreign body is not an uncommon condition, but reliable
      epidemiological data are not available. The diagnosis and management can present
      a significant challenge due to delayed presentation and the reluctance of the
      patients to provide details of the incident. The aim of the clinical evaluation
      is to identify the type, number, size, shape and location of the foreign body.
      Removal of retained rectal foreign bodies requires experience, with particular
      attention to different methods of extracting various objects. Most retained
      rectal foreign bodies can be successfully extracted transanally under appropriate
      anaesthesia and only a small proportion, mostly cases of perforation, overt
      peritonitis, pelvic sepsis or for failure of transanal extraction, will require
      open surgery or laparoscopy. It is mandatory to perform a proctosigmoidoscopy
      after anorectal foreign body removal to exclude bowel injury and ensure that the
      patient has not inserted more than one foreign body. Patients with mucosal
      abrasion, tears and oedema are to be admitted for a period of observation.

PMID- 22993142
TI  - Shape variation in outline shapes.
AB  - A general morphometric method for describing shape variation in a sample
      consisting of landmarks and multiple outline shapes is developed in this article.
      A distance metric is developed for such data and is used to embed the data in a
      low-dimensional Euclidean space. The Euclidean space is used to generate summary
      statistics such as mean and principal shape variation which are implicitly
      represented in the original space using elements of the sample. A new distance
      metric for outline shapes is proposed based on Procrustes distance that does not
      require the extraction of discrete points along the curve. The outline distance
      metric can be naturally combined with distances between landmarks. A method for
      aligning outlines and multiple outlines is developed that minimizes the distance
      metric. The method is compared with semilandmarks on synthetic data and 2 real
      data sets. Outline methods produce useful and valid results when suitably
      constrained by landmarks and are useful visualization aids, but questions remain
      about their suitability for answering biological questions until appropriate
      distance metrics can be biologically validated.

PMID- 22993141
TI  - Drosophila Psf2 has a role in chromosome condensation.
AB  - The condensation state of chromosomes is a critical parameter in multiple
      processes within the cell. Failures in the maintenance of appropriate
      condensation states may lead to genomic instability, mis-expression of genes, and
      a number of disease states. During cell proliferation, replication of DNA
      represents an ongoing challenge for chromosome packaging as DNA must be
      unpackaged for replication and then faithfully repackaged. An integral member of
      the DNA replication machinery is the GINS complex which has been shown to
      stabilize the CMG complex which is required for processivity of the Mcm2-7
      helicase complex during S phase. Through examination of the phenotypes associated
      with a null mutation in Psf2, a member of the evolutionarily conserved GINS
      complex, we find that Drosophila Psf2 likely has a role in establishing
      chromosome condensation and that the defects associated with this mis
      condensation impact M phase progression, genomic stability, and transcriptional
      regulation.

PMID- 22993143
TI  - Genetically engineered cancer models, but not xenografts, faithfully predict
      anticancer drug exposure in melanoma tumors.
AB  - BACKGROUND: Rodent studies are a vital step in the development of novel
      anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and
      efficacy studies. Traditionally, anticancer drug development has relied on
      xenograft implantation of human cancer cell lines in immunocompromised mice for
      efficacy screening of a candidate compound. The usefulness of xenograft models
      for efficacy testing, however, has been questioned, whereas genetically
      engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may
      offer some advantages for efficacy assessment. A critical factor influencing the
      predictability of rodent tumor models is drug PKs, but a comprehensive comparison
      of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human
      patients has not been performed. METHODS: In this work, we evaluated the plasma
      and tumor dispositions of an antimelanoma agent, carboplatin, in patients with
      cutaneous melanoma compared with four different murine melanoma models (one GEMM,
      one human cell line xenograft, and two OSTs). RESULTS: Using microdialysis to
      sample carboplatin tumor disposition, we found that OSTs and xenografts were poor
      predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK
      parameters similar to those seen in human tumors. CONCLUSIONS: The tumor PKs of
      carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in
      patients with melanoma than transplanted tumor models. GEMMs show promise in
      becoming an improved prediction model for intratumoral PKs and response in
      patients with solid tumors.

PMID- 22993144
TI  - Ataxia telangiectasia mutated kinase controls chronic gammaherpesvirus infection.
AB  - Gammaherpesviruses, such as Epstein-Barr virus (EBV), are ubiquitous cancer
      associated pathogens that interact with DNA damage response, a tumor suppressor
      network. Chronic gammaherpesvirus infection and pathogenesis in a DNA damage
      response-insufficient host are poorly understood. Ataxia-telangiectasia (A-T) is
      associated with insufficiency of ataxia-telangiectasia mutated (ATM), a critical
      DNA damage response kinase. A-T patients display a pattern of anti-EBV antibodies
      suggestive of poorly controlled EBV replication; however, parameters of chronic
      EBV infection and pathogenesis in the A-T population remain unclear. Here we
      demonstrate that chronic gammaherpesvirus infection is poorly controlled in an
      animal model of A-T. Intriguingly, in spite of a global increase in T cell
      activation and numbers in wild-type (wt) and ATM-deficient mice in response to
      mouse gammaherpesvirus 68 (MHV68) infection, the generation of an MHV68-specific
      immune response was altered in the absence of ATM. Our finding that ATM
      expression is necessary for an optimal adaptive immune response against
      gammaherpesvirus unveils an important connection between DNA damage response and
      immune control of chronic gammaherpesvirus infection, a connection that is likely
      to impact viral pathogenesis in an ATM-insufficient host.

PMID- 22993145
TI  - Overexpression of the ubiquitin-specific protease 7 resulting from transfection
      or mutations in the ICP0 binding site accelerates rather than depresses herpes
      simplex virus 1 gene expression.
AB  - Earlier studies reported that ICP0, a key regulatory protein encoded by herpes
      simplex virus 1 (HSV-1), binds ubiquitin-specific protease 7 (USP7). The
      fundamental conclusion of these studies is that depletion of USP7 destabilized
      ICP0, that ICP0 mediated the degradation of USP7, and that amino acid
      substitutions in ICP0 that abolished binding to USP7 significantly impaired the
      ability of HSV-1 to replicate. We show here that, indeed, depletion of USP7 leads
      to reduction of ICP0 and that USP7 is degraded in an ICP0-dependent manner.
      However, overexpression of USP7 or substitution in ICP0 of a single amino acid to
      abolish binding to USP7 accelerated the accumulation of viral mRNAs and proteins
      at early times after infection and had no deleterious effect on virus yields. A
      clue as to why USP7 is degraded emerged from the observation that,
      notwithstanding the accelerated expression of viral genes, the plaques formed by
      the mutant virus were very small, implying a defect in virus transmission from
      cell to cell.

PMID- 22993146
TI  - Kaposi's sarcoma-associated herpesvirus ORF57 is not a bona fide export factor.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV [human herpesvirus 8; HHV-8]) open
      reading frame 57 (ORF57) is a viral early protein participating in
      posttranscriptional regulatory events, such as splicing, RNA stabilization, and
      protein expression. Recent data suggest that ORF57 recruits the transcription and
      export (TREX) complex to viral RNA and exports these transcripts to the
      cytoplasm. In this study, we show that although ORF57 promotes expression of a
      selection of KSHV viral intronless RNAs, it is not a bona fide export factor.

PMID- 22993147
TI  - Evidence supporting a zoonotic origin of human coronavirus strain NL63.
AB  - The relationship between bats and coronaviruses (CoVs) has received considerable
      attention since the severe acute respiratory syndrome (SARS)-like CoV was
      identified in the Chinese horseshoe bat (Rhinolophidae) in 2005. Since then,
      several bats throughout the world have been shown to shed CoV sequences, and
      presumably CoVs, in the feces; however, no bat CoVs have been isolated from
      nature. Moreover, there are very few bat cell lines or reagents available for
      investigating CoV replication in bat cells or for isolating bat CoVs adapted to
      specific bat species. Here, we show by molecular clock analysis that
      alphacoronavirus (alpha-CoV) sequences derived from the North American tricolored
      bat (Perimyotis subflavus) are predicted to share common ancestry with human CoV
      (HCoV)-NL63, with the most recent common ancestor between these viruses occurring
      approximately 563 to 822 years ago. Further, we developed immortalized bat cell
      lines from the lungs of this bat species to determine if these cells were capable
      of supporting infection with HCoVs. While SARS-CoV, mouse-adapted SARS-CoV
      (MA15), and chimeric SARS-CoVs bearing the spike genes of early human strains
      replicated inefficiently, HCoV-NL63 replicated for multiple passages in the
      immortalized lung cells from this bat species. These observations support the
      hypothesis that human CoVs are capable of establishing zoonotic-reverse zoonotic
      transmission cycles that may allow some CoVs to readily circulate and exchange
      genetic material between strains found in bats and other mammals, including
      humans.

PMID- 22993148
TI  - Insights into avian influenza virus pathogenicity: the hemagglutinin precursor
      HA0 of subtype H16 has an alpha-helix structure in its cleavage site with
      inefficient HA1/HA2 cleavage.
AB  - With a new serotype (H17) of hemagglutinin (HA) recently being discovered, there
      are now 17 serotypes (H1 to H17) of influenza A viruses in total. It is believed
      that HA is initially expressed as a precursor of HA0 and then cleaved into HA1
      and HA2, forming a disulfide bond-linked complex, for its full function.
      Structural data show that a loop structure exists in the cleavage site between
      HA1 and HA2, and this flexible loop is crucial for the efficient cleavage of HA0.
      Here, the crystal structures of H16 (a low-pathogenicity avian influenza virus)
      in their HA0 form (H16HA0) have been solved at 1.7-A and 2.0-A resolutions. To
      our surprise, an alpha-helix element in the cleavage site which inserts into the
      negatively charged cavity with the key residue R329 hidden behind the helix was
      observed. In vitro trypsin cleavage experiments demonstrated inefficient cleavage
      of H16HA0 under both neutral and low-pH conditions. The results provide new
      insights into influenza A virus pathogenicity; both the relatively stable alpha
      helix structure in the flexible cleavage loop and inaccessibility of the cleavage
      site likely contribute to the low pathogenicity of avian influenza A virus.
      Furthermore, compared to all of the HAs whose structures have been solved, H16 is
      a good reference for assigning the HA subtypes into two groups on the basis of
      the three-dimensional structure, which is consistent with the phylogenetic
      grouping. We conclude that in light of the current H16HA0 structure, the natural
      alpha-helix element might provide a new opportunity for influenza virus inhibitor
      design.

PMID- 22993149
TI  - Regulation of paramyxovirus fusion activation: the hemagglutinin-neuraminidase
      protein stabilizes the fusion protein in a pretriggered state.
AB  - The hemagglutinin (HA)-neuraminidase protein (HN) of paramyxoviruses carries out
      three discrete activities, each of which affects the ability of HN to promote
      viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and
      triggering of the fusion protein. Binding of HN to its sialic acid receptor on a
      target cell triggers its activation of the fusion protein (F), which then inserts
      into the target cell and mediates the membrane fusion that initiates infection.
      We provide new evidence for a fourth function of HN: stabilization of the F
      protein in its pretriggered state before activation. Influenza virus
      hemagglutinin protein (uncleaved HA) was used as a nonspecific binding protein to
      tether F-expressing cells to target cells, and heat was used to activate F,
      indicating that the prefusion state of F can be triggered to initiate structural
      rearrangement and fusion by temperature. HN expression along with uncleaved HA
      and F enhances the F activation if HN is permitted to engage the receptor.
      However, if HN is prevented from engaging the receptor by the use of a small
      compound, temperature-induced F activation is curtailed. The results indicate
      that HN helps stabilize the prefusion state of F, and analysis of a stalk domain
      mutant HN reveals that the stalk domain of HN mediates the F-stabilization
      effect.

PMID- 22993150
TI  - Hepatitis C virus infection suppresses GLUT2 gene expression via downregulation
      of hepatocyte nuclear factor 1alpha.
AB  - Hepatitis C virus (HCV) infection causes not only intrahepatic diseases but also
      extrahepatic manifestations, including type 2 diabetes. We previously reported
      that HCV replication suppresses cellular glucose uptake by downregulation of cell
      surface expression of glucose transporter 2 (GLUT2) (D. Kasai et al., J. Hepatol.
      50:883-894, 2009). GLUT2 mRNA levels were decreased in both HCV RNA replicon
      cells and HCV J6/JFH1-infected cells. To elucidate molecular mechanisms of HCV
      induced suppression of GLUT2 gene expression, we analyzed transcriptional
      regulation of the GLUT2 promoter using a series of GLUT2 promoter-luciferase
      reporter plasmids. HCV-induced suppression of GLUT2 promoter activity was
      abrogated when the hepatocyte nuclear factor 1alpha (HNF-1alpha)-binding motif
      was deleted from the GLUT2 promoter. HNF-1alpha mRNA levels were significantly
      reduced in HCV J6/JFH1-infected cells. Furthermore, HCV infection remarkably
      decreased HNF-1alpha protein levels. We assessed the effects of proteasome
      inhibitor or lysosomal protease inhibitors on the HCV-induced reduction of HNF
      1alpha protein levels. Treatment of HCV-infected cells with a lysosomal protease
      inhibitor, but not with a proteasome inhibitor, restored HNF-1alpha protein
      levels, suggesting that HCV infection promotes lysosomal degradation of HNF
      1alpha protein. Overexpression of NS5A protein enhanced lysosomal degradation of
      HNF-1alpha protein and suppressed GLUT2 promoter activity. Immunoprecipitation
      analyses revealed that the region from amino acids 1 to 126 of the NS5A domain I
      physically interacts with HNF-1alpha protein. Taken together, our results suggest
      that HCV infection suppresses GLUT2 gene expression via downregulation of HNF
      1alpha expression at transcriptional and posttranslational levels. HCV-induced
      downregulation of HNF-1alpha expression may play a crucial role in glucose
      metabolic disorders caused by HCV.

PMID- 22993151
TI  - Antiviral T cell response triggers cytomegalovirus hepatitis in mice.
AB  - One common sign of human cytomegalovirus infection is altered liver function.
      Murine cytomegalovirus strain v70 induces a rapid and severe hepatitis in
      immunocompetent mice that requires the presence of T cells in order to develop.
      v70 exhibits approximately 10-fold-greater virulence than the commonly used
      strain K181, resulting in a more severe, sustained, and lethal hepatitis but not
      dramatically higher viral replication levels. Hepatitis and death are markedly
      delayed in immunodeficient SCID compared to immunocompetent BALB/c mice. Transfer
      of BALB/c splenocytes to SCID mice conferred rapid disease following infection,
      and depletion of either CD4 or CD8 T cells in BALB/c mice reduced virus-induced
      hepatitis. The frequency of CD8 T cells producing gamma interferon and tumor
      necrosis factor in response to viral antigen was higher in settings where more
      severe disease occurred. Thus, virus-specific effector CD8 T cells appear to
      contribute to lethal virus-induced hepatitis, contrasting their protective role
      during sublethal infection. This study reveals how protection and disease during
      cytomegalovirus infection depend on viral strain and dose, as well as the quality
      of the T cell response.

PMID- 22993152
TI  - Neutralizing capacity of monoclonal antibodies that recognize peptide sequences
      underlying the carbohydrates on gp41 of simian immunodeficiency virus.
AB  - Extensive glycosylation of the envelope spikes of human and simian
      immunodeficiency virus (HIV and SIV) is an important factor for the resistance of
      these viruses to neutralization by antibodies. SIVmac239 gp41 has three closely
      spaced sites for N-linked carbohydrate attachment. Rhesus macaques experimentally
      infected with mutant versions of SIVmac239 lacking two or three of these
      carbohydrate sites developed strong serum reactivity against mutated peptide
      sequences at the site of these glycosylations, as well as high titers of
      neutralizing activity to the mutant viruses (E. Yuste et al., J. Virol. 82:12472
      12486, 2008). However, whether antibodies that recognize these underlying
      peptides have neutralizing activity has not been directly demonstrated. Here we
      describe the isolation and characterization of three gp41-specific monoclonal
      antibodies (4G8, 6G8, and 7D6) from one of these mutant-infected monkeys. All
      three antibodies reacted with mutant gp41 from viral particles and also with
      peptides corresponding to mutated sequences. Slight differences in peptide
      specificities were observed among the three antibodies. Sequence analysis
      revealed that the heavy chains of all three antibodies were derived from the same
      germ line heavy-chain segment (IGHV4-59*01), but they all had very different
      sequences in complementarity-determining region 3. The light chains of all three
      antibodies were very closely related to one another. All three antibodies had
      neutralizing activity to mutant viruses deficient in gp41 carbohydrate
      attachment, but they did not neutralize the parental SIVmac239. These results
      demonstrate unambiguously that antibodies with specificity for peptide sequences
      underlying gp41 carbohydrates can effectively neutralize SIV when these
      carbohydrates are absent. However, the presence of these gp41 carbohydrates
      effectively shields the virus from antibodies that would otherwise neutralize
      viral infectivity.

PMID- 22993153
TI  - Contribution of NS1 effector domain dimerization to influenza A virus replication
      and virulence.
AB  - Conserved tryptophan-187 facilitates homodimerization of the influenza A virus
      NS1 protein effector domain. We generated a mutant influenza virus strain
      expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein
      exhibited lower double-stranded RNA (dsRNA)-binding activity, showed a temporal
      redistribution during infection, and was minimally compromised for interferon
      antagonism. The mutant virus replicated similarly to the wild type in vitro, but
      it was slightly attenuated for replication in mice, causing notably reduced
      morbidity and mortality. These data suggest biological relevance for the W187
      mediated homotypic interaction of NS1.

PMID- 22993154
TI  - Dynamics of the establishment of systemic Potyvirus infection: independent yet
      cumulative action of primary infection sites.
AB  - In the clinic, farm, or field, for many viruses there is a high prevalence of
      mixed-genotype infections, indicating that multiple virions have initiated
      infection and that there can be multiple sites of primary infection within the
      same host. The dynamic process by which multiple primary infection sites interact
      with each other and the host is poorly understood, undoubtedly due to its high
      complexity. In this study, we attempted to unravel the basic interactions
      underlying this process using a plant RNA virus, as removing the inoculated leaf
      can instantly and rigorously eliminate all primary infection sites. Effective
      population size in the inoculated leaf and time of removal of the inoculated leaf
      were varied in experiments, and it was found that both factors positively
      influenced if the plant became systemically infected and what proportion of cells
      in the systemic tissue were infected, as measured by flow cytometry. Fitting of
      probabilistic models of infection to our data demonstrated that a null model in
      which the action of each focus is independent of the presence of other foci was
      better supported than a dependent-action model. The cumulative effect of
      independently acting foci therefore determined when plants became infected and
      how many individual cells were infected. There was no evidence for interference
      between primary infection sites, which is surprising given the planar structure
      of leaves. By showing that a simple null model is supported, we experimentally
      confirmed--to our knowledge for the first time--the minimal components that
      dictate interactions of a conspecific virus population establishing systemic
      infection.

PMID- 22993155
TI  - A 205-nucleotide deletion in the 3' untranslated region of avian leukosis virus
      subgroup J, currently emergent in China, contributes to its pathogenicity.
AB  - In the past 5 years, an atypical clinical outbreak of avian leukosis virus
      subgroup J (ALV-J), which contains a unique 205-nucleotide deletion in its 3'
      untranslated region (3'UTR), has become epidemic in chickens in China. To
      determine the role of the 205-nucleotide deletion in the pathogenicity of ALV-J,
      a pair of viruses were constructed and rescued. The first virus was an ALV-J
      Chinese isolate (designated HLJ09SH01) containing the 205-nucleotide deletion in
      its 3'UTR. The second virus was a chimeric clone in which the 3'UTR contains a
      205-nucleotide sequence corresponding to a region of the ALV-J prototype virus.
      The replication and pathogenicity of the rescued viruses (rHLJ09SH01 and
      rHLJ09SH01A205) were investigated. Compared to rHLJ09SH01A205, rHLJ09SH01 showed
      a moderate growth advantage in vitro and in vivo, in addition to exhibiting a
      higher oncogenicity rate and lethality rate in layers and broilers. Increased
      vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth
      receptor subtype 2 (VEGFR-2) expression was induced by rHLJ09SH01 more so than by
      rHLJ09SH01A205 during early embryonic vascular development, but this increased
      expression disappeared when the expression levels were normalized to the viral
      levels. This finding suggests that the expression of VEGF-A and VEGFR-2 is
      associated with viral replication and may also represent a novel molecular
      mechanism underlying the oncogenic potential of ALV-J. Overall, our findings not
      only indicate that the unique 205-nucleotide deletion in the ALV-J genome
      occurred naturally in China and contributes to increased pathogenicity but also
      point to the possible mechanism of ALV-J-induced oncogenicity.

PMID- 22993156
TI  - Rift Valley fever virus strain MP-12 enters mammalian host cells via caveola
      mediated endocytosis.
AB  - Rift Valley fever virus (RVFV) is a zoonotic pathogen capable of causing serious
      morbidity and mortality in both humans and livestock. The lack of efficient
      countermeasure strategies, the potential for dispersion into new regions, and the
      pathogenesis in humans and livestock make RVFV a serious public health concern.
      The receptors, cellular factors, and entry pathways used by RVFV and other
      members of the family Bunyaviridae remain largely uncharacterized. Here we
      provide evidence that RVFV strain MP-12 uses dynamin-dependent caveola-mediated
      endocytosis for cell entry. Caveolae are lipid raft domains composed of caveolin
      (the main structural component), cholesterol, and sphingolipids. Caveola-mediated
      endocytosis is responsible for the uptake of a wide variety of host ligands, as
      well as bacteria, bacterial toxins, and a number of viruses. To determine the
      cellular entry mechanism of RVFV, we used small-molecule inhibitors, RNA
      interference (RNAi), and dominant negative (DN) protein expression to inhibit the
      major mammalian cell endocytic pathways. Inhibitors and RNAi specific for
      macropinocytosis and clathrin-mediated endocytosis had no effect on RVFV
      infection. In contrast, inhibitors of caveola-mediated endocytosis, and RNAi
      targeted to caveolin-1 and dynamin, drastically reduced RVFV infection in
      multiple cell lines. Expression of DN caveolin-1 also reduced RVFV infection
      significantly, while expression of DN EPS15, a protein required for the assembly
      of clathrin-coated pits, and DN PAK-1, an obligate mediator of macropinocytosis,
      had no significant impact on RVFV infection. These results together suggest that
      the primary mechanism of RVFV MP-12 uptake is dynamin-dependent, caveolin-1
      mediated endocytosis.

PMID- 22993157
TI  - Foot-and-mouth disease virus induces autophagosomes during cell entry via a class
      III phosphatidylinositol 3-kinase-independent pathway.
AB  - Autophagy is an intracellular pathway that can contribute to innate antiviral
      immunity by delivering viruses to lysosomes for degradation or can be beneficial
      for viruses by providing specialized membranes for virus replication. Here, we
      show that the picornavirus foot-and-mouth disease virus (FMDV) induces the
      formation of autophagosomes. Induction was dependent on Atg5, involved processing
      of LC3 to LC3II, and led to a redistribution of LC3 from the cytosol to punctate
      vesicles indicative of authentic autophagosomes. Furthermore, FMDV yields were
      reduced in cells lacking Atg5, suggesting that autophagy may facilitate FMDV
      infection. However, induction of autophagosomes by FMDV appeared to differ from
      starvation, as the generation of LC3 punctae was not inhibited by wortmannin,
      implying that FMDV-induced autophagosome formation does not require the class III
      phosphatidylinositol 3-kinase (PI3-kinase) activity of vps34. Unlike other
      picornaviruses, for which there is strong evidence that autophagosome formation
      is linked to expression of viral nonstructural proteins, FMDV induced
      autophagosomes very early during infection. Furthermore, autophagosomes could be
      triggered by either UV-inactivated virus or empty FMDV capsids, suggesting that
      autophagosome formation was activated during cell entry. Unlike other
      picornaviruses, FMDV-induced autophagosomes did not colocalize with the viral 3A
      or 3D protein. In contrast, ~50% of the autophagosomes induced by FMDV
      colocalized with VP1. LC3 and VP1 also colocalized with the cellular adaptor
      protein p62, which normally targets ubiquitinated proteins to autophagosomes.
      These results suggest that FMDV induces autophagosomes during cell entry to
      facilitate infection, but not to provide membranes for replication.

PMID- 22993158
TI  - Bacteriophage P70: unique morphology and unrelatedness to other Listeria
      bacteriophages.
AB  - Listeria monocytogenes is an important food-borne pathogen, and its
      bacteriophages find many uses in detection and biocontrol of its host. The novel
      broad-host-range virulent phage P70 has a unique morphology with an elongated
      capsid. Its genome sequence was determined by a hybrid sequencing strategy
      employing Sanger and PacBio techniques. The P70 genome contains 67,170 bp and 119
      open reading frames (ORFs). Our analyses suggest that P70 represents an archetype
      of virus unrelated to other known Listeria bacteriophages.

PMID- 22993159
TI  - Toward a hepatitis C virus vaccine: the structural basis of hepatitis C virus
      neutralization by AP33, a broadly neutralizing antibody.
AB  - The E2 envelope glycoprotein of hepatitis C virus (HCV) binds to the host entry
      factor CD81 and is the principal target for neutralizing antibodies (NAbs). Most
      NAbs recognize hypervariable region 1 on E2, which undergoes frequent mutation,
      thereby allowing the virus to evade neutralization. Consequently, there is great
      interest in NAbs that target conserved epitopes. One such NAb is AP33, a mouse
      monoclonal antibody that recognizes a conserved, linear epitope on E2 and
      potently neutralizes a broad range of HCV genotypes. In this study, the X-ray
      structure of AP33 Fab in complex with an epitope peptide spanning residues 412 to
      423 of HCV E2 was determined to 1.8 A. In the complex, the peptide adopts a beta
      hairpin conformation and docks into a deep binding pocket on the antibody. The
      major determinants of antibody recognition are E2 residues L413, N415, G418, and
      W420. The structure is compared to the recently described HCV1 Fab in complex
      with the same epitope. Interestingly, the antigen-binding sites of HCV1 and AP33
      are completely different, whereas the peptide conformation is very similar in the
      two structures. Mutagenesis of the peptide-binding residues on AP33 confirmed
      that these residues are also critical for AP33 recognition of whole E2,
      confirming that the peptide-bound structure truly represents AP33 interaction
      with the intact glycoprotein. The slightly conformation-sensitive character of
      the AP33-E2 interaction was explored by cross-competition analysis and alanine
      scanning mutagenesis. The structural details of this neutralizing epitope provide
      a starting point for the design of an immunogen capable of eliciting AP33-like
      antibodies.

PMID- 22993160
TI  - Variations in hypovirus interactions with the fungal-host RNA-silencing antiviral
      defense response.
AB  - Hypoviruses Cryphonectria hypovirus 1 (CHV-1)/EP713, CHV-1/Euro7, and CHV
      1/EP721, which infect the chestnut blight fungus Cryphonectria parasitica, differ
      in their degrees of virulence attenuation (hypovirulence), symptom expression,
      and viral RNA accumulation, even though they share between 90% and 99% amino acid
      sequence identity. In this report we examine whether this variability is
      influenced by interactions with the C. parasitica Dicer gene dcl2-dependent RNA
      silencing antiviral defense response. The mild symptoms exhibited by strains
      infected with CHV-1/Euro7 and CHV-1/EP721 relative to those with severe hypovirus
      CHV-1/EP713 did not correlate with a higher induction of the RNA-silencing
      pathway. Rather, dcl2 transcripts accumulated to a higher level (~8-fold)
      following infection by CHV-1/EP713 than following infection by CHV-1/Euro7 (1.2
      fold) or CHV-1/EP721 (1.4-fold). The differences in dcl2 transcript accumulation
      in response to CHV-1/EP713 and CHV-1/EP721 were unrelated to the suppressor of
      RNA silencing, p29, encoded by the two viruses. Moreover, the coding strand viral
      RNA levels increased by 33-, 32-, and 16-fold for CHV-1/EP713, CHV-1/Euro7, and
      CHV-1/EP721, respectively, in Deltadcl2 mutant strains. This indicates that a
      very robust antiviral RNA-silencing response was induced against all three
      viruses, even though significant differences in the levels of dcl2 transcript
      accumulation were observed. Unexpectedly, the severe debilitation previously
      reported for CHV-1/EP713-infected Deltadcl2 mutant strains, and observed here for
      the CHV-1/Euro7-infected Deltadcl2 mutant strains, was not observed with
      infection by CHV-1/EP721. By constructing chimeric viruses containing portions of
      CHV-1/EP713 and CHV-1/EP721, it was possible to map the region that is associated
      with the severe debilitation of the Deltadcl2 mutant hosts to a 4.1-kb coding
      domain located in the central part of the CHV-1/EP713 genome.

PMID- 22993161
TI  - Characterization of conserved region 2-deficient mutants of the cytomegalovirus
      egress protein pM53.
AB  - Dominant-negative (DN) mutants are powerful tools for studying essential protein
      protein interactions. A systematic genetic screen of the essential murine
      cytomegalovirus (MCMV) protein pM53 identified the accumulation of inhibitory
      mutations within conserved region 2 (CR2) and CR4. The strong inhibitory
      potential of these CR4 mutants is characterized by a particular phenotype. The DN
      effect of the small insertion mutations in CR2 was too weak to analyze (M. Popa,
      Z. Ruzsics, M. Lotzerich, L. Dolken, C. Buser, P. Walther, and U. H. Koszinowski,
      J. Virol. 84:9035-9046, 2010); therefore, the present study describes the
      construction of M53 alleles lacking CR2 (either completely or partially) and
      subsequent examination of the DN effect on MCMV replication upon conditional
      expression. Overexpression of CR2-deficient pM53 inhibited virus production by
      about 10,000-fold. This was due to interference with capsid export from the
      nucleus and viral genome cleavage/packaging. In addition, the fate of the nuclear
      envelopment complex in the presence of DN pM53 overexpression was analyzed. The
      CR2 mutants were able to bind to pM50, albeit to a lesser extent than the wild
      type protein, and relocalized the wild-type nuclear envelope complex in infected
      cells. Unlike the CR4 DN, the CR2 DN mutants did not affect the stability of
      pM50.

PMID- 22993162
TI  - A herpes simplex virus 2 glycoprotein D mutant generated by bacterial artificial
      chromosome mutagenesis is severely impaired for infecting neuronal cells and
      infects only Vero cells expressing exogenous HVEM.
AB  - We constructed a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome
      (BAC) clone, bHSV2-BAC38, which contains full-length HSV-2 inserted into a BAC
      vector. Unlike previously reported HSV-2 BAC clones, the virus genome inserted
      into this BAC clone has no known gene disruptions. Virus derived from the BAC
      clone had a wild-type phenotype for growth in vitro and for acute infection,
      latency, and reactivation in mice. HVEM, expressed on epithelial cells and
      lymphocytes, and nectin-1, expressed on neurons and epithelial cells, are the two
      principal receptors used by HSV to enter cells. We used the HSV-2 BAC clone to
      construct an HSV-2 glycoprotein D mutant (HSV2-gD27) with point mutations in
      amino acids 215, 222, and 223, which are critical for the interaction of gD with
      nectin-1. HSV2-gD27 infected cells expressing HVEM, including a human epithelial
      cell line. However, the virus lost the ability to infect cells expressing only
      nectin-1, including neuronal cell lines, and did not infect ganglia in mice.
      Surprisingly, we found that HSV2-gD27 could not infect Vero cells unless we
      transduced the cells with a retrovirus expressing HVEM. High-level expression of
      HVEM in Vero cells also resulted in increased syncytia and enhanced cell-to-cell
      spread in cells infected with wild-type HSV-2. The inability of the HSV2-gD27
      mutant to infect neuronal cells in vitro or sensory ganglia in mice after
      intramuscular inoculation suggests that this HSV-2 mutant might be an attractive
      candidate for a live attenuated HSV-2 vaccine.

PMID- 22993163
TI  - Functional redundancy in HIV-1 viral particle assembly.
AB  - Expression of a retroviral Gag protein in mammalian cells leads to the assembly
      of virus particles. In vitro, recombinant Gag proteins are soluble but assemble
      into virus-like particles (VLPs) upon addition of nucleic acid. We have proposed
      that Gag undergoes a conformational change when it is at a high local
      concentration and that this change is an essential prerequisite for particle
      assembly; perhaps one way that this condition can be fulfilled is by the
      cooperative binding of Gag molecules to nucleic acid. We have now characterized
      the assembly in human cells of HIV-1 Gag molecules with a variety of defects,
      including (i) inability to bind to the plasma membrane, (ii) near-total inability
      of their capsid domains to engage in dimeric interaction, and (iii) drastically
      compromised ability to bind RNA. We find that Gag molecules with any one of these
      defects still retain some ability to assemble into roughly spherical objects with
      roughly correct radius of curvature. However, combination of any two of the
      defects completely destroys this capability. The results suggest that these three
      functions are somewhat redundant with respect to their contribution to particle
      assembly. We suggest that they are alternative mechanisms for the initial
      concentration of Gag molecules; under our experimental conditions, any two of the
      three is sufficient to lead to some semblance of correct assembly.

PMID- 22993164
TI  - A network of protein interactions around the herpes simplex virus tegument
      protein VP22.
AB  - Assembly of the herpesvirus tegument is poorly understood but is believed to
      involve interactions between outer tegument proteins and the cytoplasmic domains
      of envelope glycoproteins. Here, we present the detailed characterization of a
      multicomponent glycoprotein-tegument complex found in herpes simplex virus 1 (HSV
      1)-infected cells. We demonstrate that the tegument protein VP22 bridges a
      complex between glycoprotein E (gE) and glycoprotein M (gM). Glycoprotein I (gI),
      the known binding partner of gE, is also recruited into this gE-VP22-gM complex
      but is not required for its formation. Exclusion of the glycoproteins gB and gD
      and VP22's major binding partner VP16 demonstrates that recruitment of virion
      components into this complex is highly selective. The immediate-early protein
      ICP0, which requires VP22 for packaging into the virion, is also assembled into
      this gE-VP22-gM-gI complex in a VP22-dependent fashion. Although subcomplexes
      containing VP22 and ICP0 can be formed when either gE or gM are absent, optimal
      complex formation requires both glycoproteins. Furthermore, and in line with
      complex formation, neither of these glycoproteins is individually required for
      VP22 or ICP0 packaging into the virion, but deletion of gE and gM greatly reduces
      assembly of both VP22 and ICP0. Double deletion of gE and gM also results in
      small plaque size, reduced virus yield, and defective secondary envelopment,
      similar to the phenotype previously shown for pseudorabies virus. Hence, we
      suggest that optimal gE-VP22-gM-gI-ICP0 complex formation correlates with
      efficient virus morphogenesis and spread. These data give novel insights into the
      poorly understood process of tegument acquisition.

PMID- 22993166
TI  - Further evidence supporting programmatic screening for, and treatment of latent
      TB Infection (LTBI) in new entrants to the UK from high TB prevalence countries.

PMID- 22993167
TI  - Are early life factors considered when managing respiratory disease? A British
      Thoracic Society survey of current practice.
AB  - BACKGROUND: We hypothesised that early life events are not routinely considered
      by most respiratory specialists. METHODS: Respiratory Specialists were surveyed
      via the British Thoracic Society (BTS) on whether they asked patients about birth
      weight, preterm birth and prenatal and postnatal complications. RESULTS: Only a
      small minority (mostly hospital paediatricians) of the 123 who replied asked most
      respiratory patients about one of more early life factors. Patient recall of the
      information when asked was low. CONCLUSIONS: The survey results suggest little
      current consideration is given to early life factors in adult respiratory
      medicine, despite increasing evidence that early life factors do impact on later
      respiratory health. Improving training, increasing awareness and exploring new
      approaches to obtaining the information are required.

PMID- 22993165
TI  - Molecular mechanism of antagonism between the Y181C and E138K mutations in HIV-1
      reverse transcriptase.
AB  - Etravirine (ETR) is an expanded-spectrum nonnucleoside reverse transcriptase
      inhibitor (NNRTI) approved for use as an antiretroviral agent in treatment
      experienced patients. Y181C and E138K in HIV-1 RT are among 20 different drug
      resistance mutations associated with ETR. However, E138K can be consistently
      selected by ETR when wild-type viruses but not viruses containing Y181C are grown
      in tissue culture. This study was carried out to evaluate any possible mechanisms
      that might explain antagonism between the Y181C and E138K mutations. Accordingly,
      we performed tissue culture studies to investigate the evolutionary dynamics of
      E138K in both a wild-type (WT) and a Y181C background. We also generated
      recombinant enzymes containing Y181C and E138K alone or in combination in order
      to study enzyme processivity, rates of processive DNA synthesis, enzyme kinetics,
      and susceptibility to ETR. We now show that the presence of the Y181C mutation
      prevented the emergence of E138K in cell culture and that the simultaneous
      presence of E138K and Y181C impaired each of enzyme activity, processivity, rate
      of processive DNA synthesis, and deoxynucleoside triphosphate (dNTP) affinity.
      The addition of E138K to Y181C also decreased the level of resistance to ETR
      compared to that obtained with Y181C alone.

PMID- 22993168
TI  - Smoking Termination Opportunity for inPatients (STOP): superiority of a course of
      varenicline tartrate plus counselling over counselling alone for smoking
      cessation: a 12-month randomised controlled trial for inpatients.
AB  - RATIONALE: Smoking cessation interventions in outpatient settings have been
      demonstrated to be cost effective. Given this evidence, we aimed to evaluate the
      effectiveness of varenicline tartrate plus Quitline-counselling compared with
      Quitline-counselling alone when initiated in the inpatient setting. METHODS:
      Adult patients (18-75 years) admitted with a smoking-related illness to three
      hospitals, were randomised to receive either 12-weeks of varenicline tartrate
      plus Quitline-counselling, (n=196) or Quitline-counselling alone, (n=196), with
      12-months follow-up. RESULTS: For the primary analysis population (intention-to
      treat), the proportion of subjects who remained continuously abstinent were
      significantly greater in the varenicline plus counselling arm (31.1%, n=61)
      compared with counselling alone (21.4%, n=42; RR 1.45, 95% CI 1.03 to 2.03,
      p=0.03). CONCLUSIONS: The combined use of varenicline plus counselling when
      initiated in the inpatient setting has produced a sustained smoking cessation
      benefit at 12-months follow-up, indicating a successful opportunistic treatment
      for smokers admitted with smoking related illnesses. TRIAL REGISTRATION:
      http://www.clinicaltrials.gov/ ClinicalTrials.gov identification number:
      NCT01141855.

PMID- 22993169
TI  - Objective measurement of compliance during oral appliance therapy for sleep
      disordered breathing.
AB  - BACKGROUND: Oral appliance (OA) therapy is increasingly prescribed as a non
      continuous positive airway pressure treatment modality for sleep-disordered
      breathing (SDB). Although OA therapy is reported to be efficacious for the
      treatment of SDB, data on compliance remain limited to self-report. METHODS: In
      this 3-month prospective clinical trial, the main outcome was to assess the
      safety and feasibility of an objective measurement of compliance during OA
      therapy using an embedded microsensor thermometer with on-chip integrated readout
      electronics in 51 consecutive patients with an established diagnosis of SDB (AHI
      18.0 +/- 11.9/h; age 47 +/- 10 y; BMI 26.6 +/- 4.0 kg/m(2); men/women: 31/20).
      Patients were unaware of the purpose of the study. RESULTS: No microsensor
      related adverse events were recorded. In addition, no problems were encountered
      during the readout of the compliance data. Out of 51 microsensors, one had a
      technical defect and was lost to follow-up. In this study, the overall objective
      mean rate of OA use was 6.6 +/- 1.3 h per day with a regular OA users' rate of
      82% at the 3-month follow-up. Statistical analysis revealed no significant
      differences between objective and self-reported OA compliance data in this study.
      Measurement of the objective OA compliance allowed us to calculate the mean
      disease alleviation (MDA) as the product of objective compliance and therapeutic
      efficacy. MDA serves as a measure of the overall therapeutic effectiveness, and
      turned out to be 51.1%. CONCLUSIONS: The results illustrate the safety and
      feasibility of objective measurement of OA compliance. The objective measurement
      of OA compliance allows for calculation of the MDA.

PMID- 22993170
TI  - Brain region-specific activity patterns after recent or remote memory retrieval
      of auditory conditioned fear.
AB  - Memory is thought to be sparsely encoded throughout multiple brain regions
      forming unique memory trace. Although evidence has established that the amygdala
      is a key brain site for memory storage and retrieval of auditory conditioned fear
      memory, it remains elusive whether the auditory brain regions may be involved in
      fear memory storage or retrieval. To investigate this possibility, we
      systematically imaged the brain activity patterns in the lateral amygdala,
      MGm/PIN, and AuV/TeA using activity-dependent induction of immediate early gene
      zif268 after recent and remote memory retrieval of auditory conditioned fear.
      Consistent with the critical role of the amygdala in fear memory, the zif268
      activity in the lateral amygdala was significantly increased after both recent
      and remote memory retrieval. Interesting, however, the density of zif268 (+)
      neurons in both MGm/PIN and AuV/TeA, particularly in layers IV and VI, was
      increased only after remote but not recent fear memory retrieval compared to
      control groups. Further analysis of zif268 signals in AuV/TeA revealed that
      conditioned tone induced stronger zif268 induction compared to familiar tone in
      each individual zif268 (+) neuron after recent memory retrieval. Taken together,
      our results support that the lateral amygdala is a key brain site for permanent
      fear memory storage and suggest that MGm/PIN and AuV/TeA might play a role for
      remote memory storage or retrieval of auditory conditioned fear, or,
      alternatively, that these auditory brain regions might have a different way of
      processing for familiar or conditioned tone information at recent and remote time
      phases.

PMID- 22993171
TI  - Administration of the phosphodiesterase type 4 inhibitor rolipram into the
      amygdala at a specific time interval after learning increases recognition memory
      persistence.
AB  - Here we show that administration of the phosphodiesterase type 4 (PDE4) inhibitor
      rolipram into the basolateral complex of the amygdala (BLA) at a specific time
      interval after training enhances memory consolidation and induces memory
      persistence for novel object recognition (NOR) in rats. Intra-BLA infusion of
      rolipram immediately, 1.5 h, or 6 h after training had no effect on retention
      tested at 1, 7, and 14 d later. However, rolipram infused 3 h post-training
      promoted memory persistence for up to at least 14 d. The findings suggest that
      PDE4 inhibition in the BLA can enhance long-term memory formation when induced
      specifically 3 h after learning.

PMID- 22993172
TI  - Commentary on 'Honorary authorship epidemic in scholarly publications? How the
      current use of citation-based evaluative metrics make (pseudo)honorary authors
      from honest contributors of every multiauthor article.'.

PMID- 22993173
TI  - Characterization of extensively drug-resistant tuberculosis cases from Valle del
      Cauca, Colombia.

PMID- 22993174
TI  - Evaluation of the FTA carrier device for human papillomavirus testing in
      developing countries.
AB  - Liquid-based methods for the collection, transportation, and storage of cervical
      cells are cumbersome and expensive and involve laborious DNA extraction. An FTA
      cartridge is a solid carrier device, easier to handle and allowing simple DNA
      elution for human papillomavirus (HPV) testing. HPV-DNA results from cervical
      specimens collected in PreservCyt medium (Hologic, Inc.) and the indicating FTA
      elute cartridge were compared in an area where transportation and storage may
      affect the performance of the test. Cervical cells from 319 young adult women
      enrolled in the Costa Rica Vaccine Trial were collected by a nurse using a Cervex
      brush (Roberts), which was placed on the FTA cartridge and subsequently rinsed in
      20 ml of PreservCyt medium. Two 0.5-ml PreservCyt aliquots were frozen for HPV
      PCR testing; the FTA cartridges were kept at room temperature. HPV-DNA detection
      and typing was performed using SPF(10) PCR/DEIA (DNA enzyme immunoassay detection
      of amplimers)/LiPA(25) system. The percent agreement, agreement among positives,
      and kappas were estimated. Positivity was higher for FTA compared to PreservCyt
      specimens (54.5% versus 45.8%, P < 0.001). For oncogenic types, the overall
      agreement was 0.92, the agreement between positives was 0.74, and the kappa was
      0.79. For individual HPV types, the overall agreement ranged from 0.97 to 1.00.
      We did not observe reduced cytology adequacy when specimen collection for
      cytology was preceded by FTA collection for HPV testing. HPV-DNA detection from
      FTA cartridges is broadly comparable to detection from PC medium. The higher HPV
      detection observed for FTA-collected specimens should be explored further. FTA
      cartridges could provide a simpler and more cost-effective method for cervical
      cell collection, storage, and transportation for HPV-DNA detection in research
      settings in developing countries.

PMID- 22993175
TI  - Laboratory detection of Enterobacteriaceae that produce carbapenemases.
AB  - A study was designed to evaluate the modified Hodge test (MHT), Mastdiscs ID
      inhibitor combination disks (MDI), Rosco Diagnostica Neo-Sensitabs (RDS), metallo
      beta-lactamase (MBL) Etest, and in-house multiplex PCR for the detection of well
      characterized carbapenemase-producing Enterobacteriaceae. One hundred forty-two
      nonrepeat clinical isolates of carbapenemase-producing Enterobacteriaceae
      (including Klebsiella spp., Escherichia coli, Citrobacter freundii, and
      Enterobacter spp.) obtained from the SMART worldwide surveillance program during
      2008 to 2009 were included. These included 49 KPC-, 27 NDM-, 19 VIM-, 14 OXA-48
      like enzyme-, and 5 IMP-producing isolates and 28 carbapenem-resistant,
      carbapenemase-negative isolates. The manufacturer's instructions were followed
      for MDI, RDS, and MBL Etest and CLSI guidelines for MHT. A multiplex PCR was
      designed to detect KPC, NDM, VIM, IMP, and OXA-48-like carbapenemases. Overall,
      the sensitivity and specificity were 78% and 93% for MDI, 80% and 93% for RDS,
      58% and 93% for MHT, and 55% and 100% for MBL Etest, respectively. The PCR had
      100% sensitivity and specificity. MDI and RDS performed well for the detection of
      KPCs and NDMs but poorly for VIMs, IMPs, and OXA-48-like enzymes. MHT performed
      well for KPCs and OXA-48-like enzymes but poorly for NDMs, VIMs, and IMPs. MDI
      and RDS were easy to perform and interpret but lacked sensitivity for OXA-48-like
      enzymes, VIMs, and IMPs. MHT and MBL Etest were often difficult to interpret. We
      recommend using molecular tests for the optimal detection of carbapenemase
      producing Enterobacteriaceae.

PMID- 22993176
TI  - Identification of clinical isolates of alpha-hemolytic streptococci by 16S rRNA
      gene sequencing, matrix-assisted laser desorption ionization-time of flight mass
      spectrometry using MALDI Biotyper, and conventional phenotypic methods: a
      comparison.
AB  - Fifty-six alpha-hemolytic streptococcal isolates were identified using MALDI
      Biotyper MS (Bruker Daltonics), API 20 Strep (bioMerieux), and BD Phoenix
      (Becton, Dickinson). The gold standard for identification was 16S rRNA gene
      sequence analysis with 16S-23S rRNA intergenic spacer sequencing. The following
      percentages of isolates were correctly identified to the species level: MALDI
      Biotyper, 46%; BD Phoenix, 35%; and API 20 Strep, 26%.

PMID- 22993177
TI  - Gardnerella vaginalis as a rare cause of prosthetic joint infection.
AB  - We describe a septic loosening of a hip prosthesis in a 71-year-old woman caused
      by Gardnerella vaginalis. Infection was confirmed by culture and molecular
      identification of this bacterium. The patient was treated by a one-step exchange
      of prosthesis and antibiotic therapy combining trimethoprim-sulfamethoxazole and
      rifampin, with favorable evolution.

PMID- 22993178
TI  - Optimization of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry analysis for bacterial identification.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) is a relatively new addition to the clinical microbiology
      laboratory. The performance of the MALDI Biotyper system (Bruker Daltonics) was
      compared to those of phenotypic and genotypic identification methods for 690
      routine and referred clinical isolates representing 102 genera and 225 unique
      species. We systematically compared direct-smear and extraction methods on a
      taxonomically diverse collection of isolates. The optimal score thresholds for
      bacterial identification were determined, and an approach to address multiple
      divergent results above these thresholds was evaluated. Analysis of
      identification scores revealed optimal species- and genus-level identification
      thresholds of 1.9 and 1.7, with 91.9% and 97.0% of isolates correctly identified
      to species and genus levels, respectively. Not surprisingly, routinely
      encountered isolates showed higher concordance than did uncommon isolates. The
      extraction method yielded higher scores than the direct-smear method for 78.3% of
      isolates. Incorrect species were reported in the top 10 results for 19.4% of
      isolates, and although there was no obvious cutoff to eliminate all of these
      ambiguities, a 10% score differential between the top match and additional
      species may be useful to limit the need for additional testing to reach single
      species-level identifications.

PMID- 22993179
TI  - Detection of severe fever with thrombocytopenia syndrome virus by reverse
      transcription-cross-priming amplification coupled with vertical flow
      visualization.
AB  - A virus known as severe fever with thrombocytopenia syndrome virus (SFTSV) was
      recently identified as the etiological agent of severe fever with
      thrombocytopenia syndrome (SFTS) in China. Reliable laboratory detection and
      identification of this virus are likely to become clinically and
      epidemiologically desirable. We developed a nearly instrument-free, simple
      molecular method which incorporates reverse transcription-cross-priming
      amplification (RT-CPA) coupled with a vertical flow (VF) visualization strip for
      rapid detection of SFTSV. The RT-CPA-VF assay targets a conserved region of the M
      segment of the SFTSV genome and has a limit of detection of 100 copies per
      reaction, with no cross-reaction with other vector-borne bunyaviruses and
      bacterial pathogens. The performance of the RT-CPA-VF assay was determined with
      175 human plasma specimens collected from 89 clinically suspected SFTS patients
      and 86 healthy donors. The sensitivity and specificity of the assay were 94.1%
      and 100.0%, respectively, compared with a combination of virus culture and real
      time RT-PCR. The entire procedure, from specimen processing to result reporting,
      can be completed within 2 h. The simplicity and nearly instrument-free platform
      of the RT-CPA-VF assay make it practical for point-of-care testing.

PMID- 22993181
TI  - Toxin detection in patients' sera by mass spectrometry during two outbreaks of
      type A Botulism in France.
AB  - In two outbreaks of food-borne botulism in France, Clostridium botulinum type A
      was isolated and characterized from incriminated foods. Botulinum neurotoxin type
      A was detected in the patients' sera by mouse bioassay and in vitro endopeptidase
      assay with an immunocapture step and identification of the cleavage products by
      mass spectrometry.

PMID- 22993180
TI  - Universal amplification, next-generation sequencing, and assembly of HIV-1
      genomes.
AB  - Whole HIV-1 genome sequences are pivotal for large-scale studies of inter- and
      intrahost evolution, including the acquisition of drug resistance mutations. The
      ability to rapidly and cost-effectively generate large numbers of HIV-1 genome
      sequences from different populations and geographical locations and determine the
      effect of minority genetic variants is, however, a limiting factor. Next
      generation sequencing promises to bridge this gap but is hindered by the lack of
      methods for the enrichment of virus genomes across the phylogenetic breadth of
      HIV-1 and methods for the robust assembly of the virus genomes from short-read
      data. Here we report a method for the amplification, next-generation sequencing,
      and unbiased de novo assembly of HIV-1 genomes of groups M, N, and O, as well as
      recombinants, that does not require prior knowledge of the sequence or subtype. A
      sensitivity of at least 3,000 copies/ml was determined by using plasma virus
      samples of known copy numbers. We applied our novel method to compare the genome
      diversities of HIV-1 groups, subtypes, and genes. The highest level of diversity
      was found in the env, nef, vpr, tat, and rev genes and parts of the gag gene.
      Furthermore, we used our method to investigate mutations associated with HIV-1
      drug resistance in clinical samples at the level of the complete genome. Drug
      resistance mutations were detected as both major variant and minor species. In
      conclusion, we demonstrate the feasibility of our method for large-scale HIV-1
      genome sequencing. This will enable the phylogenetic and phylodynamic resolution
      of the ongoing pandemic and efficient monitoring of complex HIV-1 drug resistance
      genotypes.

PMID- 22993182
TI  - Use of a prequalification panel for rapid scale-up of high-throughput HIV viral
      load testing.
AB  - Increased access to antiretroviral drugs expands needs for viral load (VL)
      testing. South Africa's National Health Laboratory Service responded to demands
      by implementing two testing platforms in 17 laboratories within 8 months. An
      industry partner's collaboration, training programs, and method verification with
      a VL prequalification panel ensured testing quality and rapid implementation.

PMID- 22993183
TI  - Performance of the GeneXpert CT/NG assay compared to that of the Aptima AC2 assay
      for detection of rectal Chlamydia trachomatis and Neisseria gonorrhoeae by use of
      residual Aptima Samples.
AB  - There are currently no commercially available molecular assays for the detection
      of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal swabs with
      regulatory approval. We compared the Cepheid GeneXpert CT/NG assay with the
      GenProbe Aptima Combo2 assay, using 409 rectal swabs. Using Aptima as the gold
      standard, the sensitivity, specificity, and positive and negative predictive
      values of GeneXpert for the detection of C. trachomatis and N. gonorrhoeae were
      86%, 99.2%, 92.5%, and 98.4% and 91.1%, 100%, 100%, and 98.6%, respectively.
      Despite significant dilution of samples prior to GeneXpert testing, the assay
      performed well with excellent specificity.

PMID- 22993184
TI  - Genotypic resistance testing creates new treatment challenges: two cases of
      oxacillin-susceptible methicillin-resistant Staphylococcus aureus.
AB  - Oxacillin-susceptible, mecA-positive Staphylococcus aureus isolates create a
      treatment challenge for the clinician. In this article, we describe two cases of
      bacteremia from isolates that carried the mecA gene but were susceptible to
      oxacillin (oxacillin-susceptible methicillin-resistant S. aureus [OS-MRSA]). DNA
      microarray analysis was used to characterize these isolates as a mecA-positive,
      clonal complex 5, pediatric strain and a mecA-positive, clonal complex 8, USA300
      strain.

PMID- 22993185
TI  - Rapid detection of Staphylococcus aureus in lower respiratory tract secretions
      from patients with suspected ventilator-associated pneumonia: evaluation of the
      Cepheid Xpert MRSA/SA SSTI assay.
AB  - A preclinical evaluation was conducted to evaluate the performance of the Cepheid
      Xpert assay on 135 lower respiratory tract secretions for detection of
      methicillin-resistant Staphylococcus aureus and S. aureus. Compared with the
      quantitative culture, the sensitivity, specificity, and positive and negative
      predictive values were 99.0%, 72.2%, 90.7%, and 96.3%, respectively.

PMID- 22993186
TI  - Single nucleotide polymorphisms in the Mycobacterium bovis genome resolve
      phylogenetic relationships.
AB  - Mycobacterium bovis isolates carry restricted allelic variation yet exhibit a
      range of disease phenotypes and host preferences. Conventional genotyping methods
      target small hypervariable regions of the M. bovis genome and provide anonymous
      biallelic information that is insufficient to develop phylogeny. To resolve
      phylogeny and establish trait-allele associations, we interrogated 75 M. bovis
      and 61 M. tuberculosis genomes for single nucleotide polymorphisms (SNPs), using
      iPLEX MassArray (Sequenom Inc., CA) technology. We indexed nucleotide variations
      in 306 genic and 44 intergenic loci among isolates derived from outbreaks in the
      United States from 1991 to 2010 and isolated from a variety of mammalian hosts.
      Two hundred six variant SNPs classified the 136 isolates and 4 previously
      sequenced strains (AF2122/97, BCG Pasteur, H37Rv, and CDC1551) into 5 major "SNP
      cluster groups." M. bovis isolates clustered into three major lineages based on
      118 variant SNPs, while 84 SNPs differentiated the M. bovis BCG lineage from the
      virulent isolates. Forty-nine of the 51 human M. tuberculosis isolates were
      identical at all 350 loci studied. Thus, SNP-based analyses resolved the
      genotypic differences within M. bovis strains and differentiated these strains
      from M. tuberculosis strains representing diversity in time and space, providing
      population genetic frameworks that may aid in identifying factors responsible for
      the wide host range and disease phenotypes of M. bovis.

PMID- 22993187
TI  - Evaluation of a simple protein extraction method for species identification of
      clinically relevant staphylococci by matrix-assisted laser desorption ionization
      time of flight mass spectrometry.
AB  - In clinical microbiology, bacterial identification is labor-intensive and time
      consuming. A solution for this problem is the use of matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In this
      study, we evaluated a modified protein extraction method of identification
      performed on target plates (on-plate extraction method) with MALDI-TOF (Bruker
      Microflex LT with Biotyper version 3.0) and compared it to 2 previously described
      methods: the direct colony method and a standard protein extraction method
      (standard extraction method). We evaluated the species of 273 clinical strains
      and 14 reference strains of staphylococci. All isolates were characterized using
      the superoxide dismutase A sequence as a reference. For the species
      identification, the on-plate, standard extraction, and direct colony methods
      identified 257 isolates (89.5%), 232 isolates (80.8%), and 173 isolates (60.2%),
      respectively, with statistically significant differences among the three methods
      (P < 0.05). In conclusion, the on-plate extraction method is at least as good as
      standard extraction in identification rate and has the advantage of a shorter
      processing time.

PMID- 22993188
TI  - NS5A sequence heterogeneity of hepatitis C virus genotype 4a predicts clinical
      outcome of pegylated-interferon-ribavirin therapy in Egyptian patients.
AB  - Hepatitis C virus genotype 4 (HCV-4) is the cause of approximately 20% of the 180
      million cases of chronic hepatitis C in the world. HCV-4 infection is common in
      the Middle East and Africa, with an extraordinarily high prevalence in Egypt.
      Viral genetic polymorphisms, especially within core and NS5A regions, have been
      implicated in influencing the response to pegylated-interferon and ribavirin (PEG
      IFN/RBV) combination therapy in HCV-1 infection. However, this has not been
      confirmed in HCV-4 infection. Here, we investigated the impact of heterogeneity
      of NS5A and core proteins of HCV-4, mostly subtype HCV-4a, on the clinical
      outcomes of 43 Egyptian patients treated with PEG-IFN/RBV. Sliding window
      analysis over the carboxy terminus of NS5A protein identified the IFN/RBV
      resistance-determining region (IRRDR) as the most prominent region associated
      with sustained virological response (SVR). Indeed, 21 (84%) of 25 patients with
      SVR, but only 5 (28%) of 18 patients with non-SVR, were infected with HCV having
      IRRDR with 4 or more mutations (IRRDR >= 4) (P = 0.0004). Multivariate analysis
      identified IRRDR >= 4 as an independent SVR predictor. The positive predictive
      value of IRRDR >= 4 for SVR was 81% (21/26; P = 0.002), while its negative
      predictive value for non-SVR was 76% (13/17; P = 0.02). On the other hand, there
      was no significant correlation between core protein polymorphisms, either at
      residue 70 or at residue 91, and treatment outcome. In conclusion, the present
      results demonstrate for the first time that IRRDR >= 4, a viral genetic
      heterogeneity, would be a useful predictive marker for SVR in HCV-4 infection
      when treated with PEG-IFN/RBV.

PMID- 22993189
TI  - Hyperediting of human T-cell leukemia virus type 2 and simian T-cell leukemia
      virus type 3 by the dsRNA adenosine deaminase ADAR-1.
AB  - RNA editing mediated by adenosine deaminases acting on RNA (ADARs) converts
      adenosine (A) to inosine (I) residues in dsRNA templates. While ADAR-1-mediated
      editing was essentially described for RNA viruses, the present work addresses the
      issue for two delta-retroviruses, human T-cell leukemia virus type 2 and simian T
      cell leukemia virus type 3 (HTLV-2 and STLV-3). We examined whether ADAR-1 could
      edit HTLV-2 and STLV-3 virus genomes in cell culture and in vivo. Using a highly
      sensitive PCR-based method, referred to as 3DI-PCR, we showed that ADAR-1 could
      hypermutate adenosine residues in HTLV-2. STLV-3 hypermutation was obtained
      without using 3DI-PCR, suggesting a higher mutation frequency for this virus.
      Detailed analysis of the dinucleotide editing context showed preferences for 5'
      ArA and 5' UrA. In conclusion, the present observations demonstrate that ADAR-1
      massively edits HTLV-2 and STLV-3 retroviruses in vitro, but probably remains a
      rare phenomenon in vivo.

PMID- 22993190
TI  - Genomic reassortment of influenza A virus in North American swine, 1998-2011.
AB  - Revealing the frequency and determinants of reassortment among RNA genome
      segments is fundamental to understanding basic aspects of the biology and
      evolution of the influenza virus. To estimate the extent of genomic reassortment
      in influenza viruses circulating in North American swine, we performed a
      phylogenetic analysis of 139 whole-genome viral sequences sampled during 1998
      2011 and representing seven antigenically distinct viral lineages. The highest
      amounts of reassortment were detected between the H3 and the internal gene
      segments (PB2, PB1, PA, NP, M and NS), while the lowest reassortment frequencies
      were observed among the H1gamma, H1pdm and neuraminidase segments, particularly
      N1. Less reassortment was observed among specific haemagglutinin-neuraminidase
      combinations that were more prevalent in swine, suggesting that some genome
      constellations may be evolutionarily more stable.

PMID- 22993191
TI  - Interclade recombination in porcine parvovirus strains.
AB  - A detailed analysis of the Ns1/Vp1Vp2 genome region of the porcine parvovirus
      (PPV) strains isolated from vaccinated animals was performed. We found many
      inconsistencies in the phylogenetic trees of these viral isolates, such as low
      statistical support and strains with long branches in the phylogenetic trees.
      Thus, we used distance-based and phylogenetic methods to distinguish de facto
      recombinants from spurious recombination signals. We found a mosaic virus in
      which the Ns1 gene was acquired from one PPV clade and the Vp1Vp2 gene was
      acquired from a distinct phylogenetic clade. We also described the interclade
      mosaic structure of the Vp1Vp2 gene of a reference strain. If recombination is an
      adaptive mechanism over the course of PPV evolution, we would likely observe
      increasing numbers of chimeric strains over time. However, when the PPV sequences
      isolated from 1964 to 2011 were analysed, only two chimeric strains were
      detected. Thus, PPV recombination is an independent event, resulting from close
      contact between animals housed in high-density conditions.

PMID- 22993192
TI  - Cell-dependent production of polyhedra and virion occlusion of Autographa
      californica multiple nucleopolyhedrovirus fp25k mutants in vitro and in vivo.
AB  - Members of the family Baculoviridae are insect-specific dsDNA viruses that have
      been used for biological control of insect pests in agriculture and forestry, as
      well as in research and pharmaceutical protein expression in insect cells and
      larvae. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the type
      species of the family Baculoviridae. During infection of AcMNPV in permissive
      cells, fp25k mutants are positively selected, leading to the formation of the few
      polyhedra (FP) phenotype with reduced yield of polyhedra and reduced virion
      occlusion efficiency, which leads to decreased oral infectivity for insects. Here
      we report that polyhedra of AcMNPV fp25k mutants produced from different insect
      cell lines and insects have differences in larval per os infectivity, and that
      these variations are due to different virion occlusion efficiencies in these cell
      lines and insects. Polyhedra of AcMNPV fp25k mutants produced from Sf cells (Sf21
      and Sf9, derived from Spodoptera frugiperda) and S. frugiperda larvae had poorer
      virion occlusion efficiency than those from Hi5 cells (derived from Trichoplusia
      ni) and T. ni larvae, based on immunoblots, DNA isolation and larval oral
      infection analysis. AcMNPV fp25k mutants formed clusters of FP and many polyhedra
      (MP) in the fat body cells of both T. ni and S. frugiperda larvae. Transmission
      electron microscopy revealed that the nature of virion occlusion of AcMNPV fp25k
      mutants was dependent on the different cells of the T. ni fat body tissue. Taken
      together, these results indicate that the FP phenotype and virion occlusion
      efficiency of fp25k mutants are influenced by the host insect cells.

PMID- 22993193
TI  - Ultrasound-guided dorsal approach for femoral nerve blockade in cats: an imaging
      study.
AB  - This study was conducted to describe and validate a dorsal ultrasound-guided
      approach to block the femoral nerve (FN) in cats by means of anatomical and
      computed tomography (CT) studies. The anatomical study was carried out in four
      fresh feline cadavers to determine the anatomic landmarks to approach this nerve.
      Then, an ultrasonographic study of the FN was performed in another eight cadavers
      using a 13 MHz linear transducer. The accuracy of the neurolocation by
      ultrasonography (US) was determined in four cadavers by the injection of 1 ml
      blue ink around the FN. The staining of the nerve was evaluated in anatomical
      studies. The feasibility of this technique was also evaluated by CT after
      injecting 1 ml of an iodinated contrast medium (150 mgl/ml) around the FN in the
      other four cadavers. The landmarks to approach the FN were the cranial border of
      the iliac crest and the dorsal processes of L6 and L7. The FN was visualised as a
      round hypoechogenic structure surrounded by a hyperechogenic rim located within
      the iliopsoas muscle on transverse scans. The anatomical and CT studies confirmed
      the accuracy of the US location of the FN. The dorsal ultrasound-guided approach
      may allow feasible and accurate access to the FN in cats and it could be useful
      in producing successful blockade.

PMID- 22993194
TI  - Gravity changes during animal development affect IgM heavy-chain transcription
      and probably lymphopoiesis.
AB  - Our previous research demonstrated that spaceflight conditions affect antibody
      production in response to an antigenic stimulation in adult amphibians. Here, we
      investigated whether antibody synthesis is affected when animal development
      occurs onboard a space station. To answer this question, embryos of the Iberian
      ribbed newt, Pleurodeles waltl, were sent to the International Space Station
      (ISS) before the initiation of immunoglobulin heavy-chain expression. Thus,
      antibody synthesis began in space. On landing, we determined the effects of
      spaceflight on P. waltl development and IgM heavy-chain transcription. Results
      were compared with those obtained using embryos that developed on Earth. We find
      that IgM heavy-chain transcription is doubled at landing and that spaceflight
      does not affect P. waltl development and does not induce inflammation. We also
      recreated the environmental modifications encountered by the embryos during their
      development onboard the ISS. This strategy allowed us to demonstrate that gravity
      change is the factor responsible for antibody heavy-chain transcription
      modifications that are associated with NF-kappaB mRNA level variations. Taken
      together, and given that the larvae were not immunized, these data suggest a
      modification of lymphopoiesis when gravity changes occur during ontogeny.

PMID- 22993195
TI  - Adjunctive beta2-agonists reverse neuromuscular involvement in murine Pompe
      disease.
AB  - Pompe disease has resisted enzyme replacement therapy with acid alpha-glucosidase
      (GAA), which has been attributed to inefficient cation-independent mannose-6
      phosphate receptor (CI-MPR) mediated uptake. We evaluated beta2-agonist drugs,
      which increased CI-MPR expression in GAA knockout (KO) mice. Clenbuterol along
      with a low-dose adeno-associated virus vector increased Rotarod latency by 75% at
      4 wk, in comparison with vector alone (P<2*10(-5)). Glycogen content was lower in
      skeletal muscles, including soleus (P<0.01), extensor digitorum longus (EDL;
      P<0.001), and tibialis anterior (P<0.05) following combination therapy, in
      comparison with vector alone. Glycogen remained elevated in the muscles following
      clenbuterol alone, indicating an adjunctive effect with gene therapy. Elderly GAA
      KO mice treated with combination therapy demonstrated 2-fold increased wirehang
      latency, in comparison with vector or clenbuterol alone (P<0.001). The glycogen
      content of skeletal muscle decreased following combination therapy in elderly
      mice (P<0.05). Finally, CI-MPR-KO/GAA-KO mice did not respond to combination
      therapy, indicating that clenbuterol's effect depended on CI-MPR expression. In
      summary, adjunctive beta2-agonist treatment increased CI-MPR expression and
      enhanced efficacy from gene therapy in Pompe disease, which has implications for
      other lysosomal storage disorders that involve primarily the brain.

PMID- 22993200
TI  - Interview with Dannie Abse.

PMID- 22993196
TI  - Hepatic ATGL knockdown uncouples glucose intolerance from liver TAG accumulation.
AB  - Adipose triglyceride lipase (ATGL) is the predominant triacylglycerol (TAG)
      hydrolase in mammals; however, the tissue-specific effects of ATGL outside of
      adipose tissue have not been well characterized. Hence, we tested the
      contribution of hepatic ATGL on mediating glucose tolerance and insulin action.
      Glucose or insulin tolerance tests and insulin signaling were performed in
      C57BL/6 mice administered control (nongene specific shRNA) or Atgl shRNA
      adenoviruses. Glucose and lipid metabolism assays were conducted in primary
      hepatocytes isolated from mice transduced with control or Atgl shRNA
      adenoviruses. Knocking down hepatic ATGL completely abrogated the increase in
      serum insulin following either 1 or 12 wk of feeding a high-fat (HF) diet despite
      higher hepatic TAG content. Glucose tolerance tests demonstrated that ATGL
      knockdown normalized glucose tolerance in HF-diet-fed mice. The observed
      improvements in glucose tolerance were present despite unaltered hepatic insulin
      signaling and increased liver TAG. Mice with suppressed hepatic ATGL had reduced
      hepatic glucose production in vivo, and hepatocytes isolated from Atgl shRNA
      treated mice displayed a 26% decrease in glucose production and a 38% increase in
      glucose oxidation compared to control cells. Taken together, these data suggest
      that hepatic ATGL knockdown enhances glucose tolerance by increasing hepatic
      glucose utilization and uncouples impairments in insulin action from hepatic TAG
      accumulation.

PMID- 22993197
TI  - Orai3 is an estrogen receptor alpha-regulated Ca2+ channel that promotes
      tumorigenesis.
AB  - Store-operated Ca(2+) entry (SOCE) encoded by Orai1 proteins is a ubiquitous
      Ca(2+)-selective conductance involved in cellular proliferation and migration. We
      recently described up-regulation of Orai3 channels that selectively mediate SOCE
      in estrogen receptor alpha-expressing (ERalpha(+)) breast cancer cells. However,
      the connection between ERalpha and Orai3 and the role of Orai3 in tumorigenesis
      remain unknown. Here, we show that ERalpha knockdown decreases Orai3 mRNA (by
      ~63%) and protein (by ~44%) with no effect on Orai1. ERalpha knockdown decreases
      Orai3-mediated SOCE (by ~43%) and the corresponding Ca(2+) release-activated
      Ca(2+) (CRAC) current (by ~42%) in ERalpha(+) MCF7 cells. The abrogation of SOCE
      in MCF7 cells on ERalpha knockdown can be rescued by ectopic expression of Orai3.
      ERalpha activation increased Orai3 expression and SOCE in MCF7 cells. Epidermal
      growth factor (EGF) and thrombin stimulate Ca(2+) influx into MCF7 cells through
      Orai3. Orai3 knockdown inhibited SOCE-dependent phosphorylation of extracellular
      signal-regulated kinase (ERK1/2; by ~44%) and focal adhesion kinase (FAK; by
      ~46%) as well as transcriptional activity of nuclear factor for activated T cells
      (NFAT; by ~49%). Significantly, Orai3 knockdown selectively decreased anchorage
      independent growth (by ~58%) and Matrigel invasion (by ~44%) of ERalpha(+) MCF7
      cells with no effect on ERalpha(-) MDA-MB231 cells. Moreover, Orai3 knockdown
      inhibited ERalpha(+) cell tumorigenesis in immunodeficient mice (~66% reduction
      in tumor volume). These data establish Orai3 as an ERalpha-regulated channel and
      a potential selective therapeutic target for ERalpha(+) breast cancers.

PMID- 22993201
TI  - Psychometric tests for diagnosing minimal hepatic encephalopathy.
AB  - While it is consensus that minimal hepatic encephalopathy (mHE) has significant
      impact on a patient's daily living, and thus should be diagnosed and treated,
      there is no consensus about the optimal diagnostic tools. At present the most
      frequently used psychometric methods for diagnosing minimal hepatic
      encephalopathy are the Inhibitory Control Test and the Psychometric Hepatic
      Encephalopathy Score PHES. Another frequently used method is Critical Flicker
      Frequency. The PHES and the Repeatable Battery for the Assessment of
      Neuropsychological Status have been recommended for diagnosing mHE by a working
      party commissioned by the International Society for Hepatic Encephalopathy and
      Nitrogen Metabolism. Recently the Continuous Reaction Time Test, which has been
      used in the 1980ies, has gained new interest. Today, no data are available that
      allow to decide which of these methods is the most appropriate. In fact, even
      basic information such as dependence on age, sex and education or influence of
      diseases that frequently accompany liver cirrhosis upon test results is missing
      for most of them. Future studies must address these questions to improve
      diagnosis of mHE.

PMID- 22993202
TI  - Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in
      inflammatory bowel diseases.
AB  - OBJECTIVE: Gut microbiota metabolises bile acids (BA). As dysbiosis has been
      reported in inflammatory bowel diseases (IBD), we aim to investigate the impact
      of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial
      cell inflammation response. DESIGN: Faecal and serum BA rates, expressed as a
      proportion of total BA, were assessed by high-performance liquid chromatography
      tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29).
      The faecal microbiota composition was assessed by quantitative real-time PCR.
      Using BA profiles and microbiota composition, cluster formation between groups
      was generated by ranking models. The faecal BA profiles in germ-free and
      conventional mice were compared. Direct enzymatic activities of BA
      biotransformation were measured in faeces. The impact of BA on the inflammatory
      response was investigated in vitro using Caco-2 cells stimulated by IL-1beta.
      RESULTS: IBD-associated dysbiosis was characterised by a decrease in the ratio
      between Faecalibacterium prausntizii and Escherichia coli. Faecal-conjugated BA
      rates were significantly higher in active IBD, whereas, secondary BA rates were
      significantly lower. Interestingly, active IBD patients exhibited higher levels
      of faecal 3-OH-sulphated BA. The deconjugation, transformation and desulphation
      activities of the microbiota were impaired in IBD patients. In vitro, secondary
      BA exerted anti-inflammatory effects, but sulphation of secondary BAs abolished
      their anti-inflammatory properties. CONCLUSIONS: Impaired microbiota enzymatic
      activity observed in IBD-associated dysbiosis leads to modifications in the
      luminal BA pool composition. Altered BA transformation in the gut lumen can erase
      the anti-inflammatory effects of some BA species on gut epithelial cells and
      could participate in the chronic inflammation loop of IBD.

PMID- 22993203
TI  - The role of IL-15 in activating STAT5 and fine-tuning IL-17A production in CD4 T
      lymphocytes.
AB  - IL-15 is an important IL-2-related cytokine whose role in Th17 cell biology has
      not been fully elucidated. In this study, we show that exogenous IL-15 decreased
      IL-17A production in Th17 cultures. Neutralization of IL-15 using an Ab led to
      increases in IL-17A production in Th17 cultures. Both Il15(-/-) and Il15r(-/-) T
      cell cultures displayed higher frequency of IL-17A producers and higher amounts
      of IL-17A in the supernatants compared with those of wild-type (WT) cells in
      vitro. IL-15 down-modulated IL-17A production independently of retinoic acid
      related orphan receptor-gammat, Foxp3, and IFN-gamma expression. Both Th17 cells
      and APCs produced IL-15, which induced binding of STAT5, an apparent repressor to
      the Il17 locus in CD4 T cells. Also, in a model of myelin oligodendrocyte
      glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), Il15(-/-)
      mice displayed exacerbated inflammation-correlating with increased IL-17A
      production by their CD4(+) T cells-compared with WT controls. Exogenous IL-15
      administration and IL-17A neutralization reduced the severity of EAE in Il15(-/-)
      mice. Taken together, these data indicate that IL-15 has a negative regulatory
      role in fine-tuning of IL-17A production and Th17-mediated inflammation.

PMID- 22993204
TI  - Dihydroartemisinin ameliorates inflammatory disease by its reciprocal effects on
      Th and regulatory T cell function via modulating the mammalian target of
      rapamycin pathway.
AB  - Dihydroartemisinin (DHA) is an important derivative of the herb medicine
      Artemisia annua L., used in ancient China. DHA is currently used worldwide to
      treat malaria by killing malaria-causing parasites. In addition to this prominent
      effect, DHA is thought to regulate cellular functions, such as angiogenesis,
      tumor cell growth, and immunity. Nonetheless, how DHA affects T cell function
      remains poorly understood. We found that DHA potently suppressed Th cell
      differentiation in vitro. Unexpectedly, however, DHA greatly promoted regulatory
      T cell (Treg) generation in a manner dependent on the TGF-betaR:Smad signal. In
      addition, DHA treatment effectively reduced onset of experimental autoimmune
      encephalomyelitis (EAE) and ameliorated ongoing EAE in mice. Administration of
      DHA significantly decreased Th but increased Tregs in EAE-inflicted mice, without
      apparent global immune suppression. Moreover, DHA modulated the mammalian target
      of rapamycin (mTOR) pathway, because mTOR signal was attenuated in T cells upon
      DHA treatment. Importantly, enhanced Akt activity neutralized DHA-mediated
      effects on T cells in an mTOR-dependent fashion. This study therefore reveals a
      novel immune regulatory function of DHA in reciprocally regulating Th and Treg
      cell generation through the modulating mTOR pathway. It addresses how DHA
      regulates immune function and suggests a new type of drug for treating diseases
      in which mTOR activity is to be tempered.

PMID- 22993207
TI  - The new era of payment reform, spending targets, and cost containment in
      Massachusetts: early lessons for the nation.
AB  - As its 2012 session drew to a close, the Massachusetts legislature passed a much
      anticipated cost control bill. The bill sets annual state spending targets,
      encourages the formation of accountable care organizations, and establishes an
      independent commission to oversee health care system performance. It is
      Massachusetts's third law to address health spending since the state's landmark
      health insurance coverage reforms in 2006. The 2012 legislation is a notable step
      beyond other recent cost control efforts. Although it lacks strong mechanisms to
      enforce the new spending goals, it creates a framework for increased regulation
      if spending trends fail to moderate. Massachusetts's experience provides several
      lessons for state and federal policy makers. First, implementing near-universal
      coverage, as is planned under the Affordable Care Act for 2014, will increase
      pressure on government to begin controlling overall health care spending. Second,
      introduction of cost control measures takes time: Massachusetts enacted a series
      of incremental but increasingly strong laws over the past six years that have
      gradually increased its ability to influence health spending. Finally, the
      effectiveness of new cost control laws will depend on changes in providers' and
      insurers' behavior; in Massachusetts, private market activity has had a
      complementary impact on the pace of health system change.

PMID- 22993205
TI  - Thymic function is maintained during Salmonella-induced atrophy and recovery.
AB  - Thymic atrophy is a frequent consequence of infection with bacteria, viruses, and
      parasites and is considered a common virulence trait between pathogens. Multiple
      reasons have been proposed to explain this atrophy, including premature egress of
      immature thymocytes, increased apoptosis, or thymic shutdown to prevent tolerance
      to the pathogen from developing. The severe loss in thymic cell number can
      reflect an equally dramatic reduction in thymic output, potentially reducing
      peripheral T cell numbers. In this study, we examine the relationship between
      systemic Salmonella infection and thymic function. During infection, naive T cell
      numbers in peripheral lymphoid organs increase. Nevertheless, this occurs despite
      a pronounced thymic atrophy caused by viable bacteria, with a peak 50-fold
      reduction in thymocyte numbers. Thymic atrophy is not dependent upon homeostatic
      feedback from peripheral T cells or on regulation of endogenous glucocorticoids,
      as demonstrated by infection of genetically altered mice. Once bacterial numbers
      fall, thymocyte numbers recover, and this is associated with increases in the
      proportion and proliferation of early thymic progenitors. During atrophy, thymic
      T cell maturation is maintained, and single-joint TCR rearrangement excision
      circle analysis reveals there is only a modest fall in recent CD4(+) thymic
      emigrants in secondary lymphoid tissues. Thus, thymic atrophy does not
      necessarily result in a matching dysfunctional T cell output, and thymic
      homeostasis can constantly adjust to systemic infection to ensure that naive T
      cell output is maintained.

PMID- 22993208
TI  - The role of circulating fibrocytes in inflammation and autoimmunity.
AB  - Autoimmunity is a chronic process resulting in inflammation, tissue damage, and
      subsequent tissue remodeling. Circulating fibrocytes are bone marrow-derived
      cells with characteristics of hematopoietic and mesenchymal cells. These cells
      have been implicated in many inflammatory and fibrotic conditions as well as in
      wound healing. Fibrocytes can amplify the inflammatory/immune response through
      multiple mechanisms, including antigen presentation, cytokine and chemokine
      secretion, and production of MMPs. Increased numbers of circulating fibrocytes
      are observed in RA, systemic scleroderma, and Graves' disease. Here, we review
      the current literature and potential involvement of fibrocytes in inflammation
      and autoimmunity.

PMID- 22993206
TI  - Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to
      intestinal homeostasis.
AB  - Although CD4(+) Th17 cells are enriched in normal intestines, their role in
      regulation of the host response to microbiota, and whether and how they
      contribute to intestinal homeostasis, is still largely unknown. It is also
      unclear whether Th17 cells regulate intestinal IgA production, which is also
      abundant in the intestinal lumen and has a crucial role as the first defense line
      in host response to microbiota. In this study, we found that intestinal polymeric
      Ig receptor (pIgR) and IgA production was impaired in T cell-deficient TCR
      betaxdelta(-/-) mice. Repletion of TCR-betaxdelta(-/-) mice with Th17 cells from
      CBir1 flagellin TCR transgenic mice, which are specific for a commensal Ag,
      increased intestinal pIgR and IgA. The levels of intestinal pIgR and IgA in B6.IL
      17R (IL-17R(-/-)) mice were lower than wild type mice. Treatment of colonic
      epithelial HT-29 cells with IL-17 increased pIgR expression. IL-17R(-/-) mice
      demonstrated systemic antimicroflora Ab response. Consistently, administering
      dextran sulfate sodium (DSS) to C57BL/6 mice after treatment with IL-17
      neutralizing Ab resulted in more severe intestinal inflammation compared with
      control Ab. Administering DSS to IL-17R(-/-) mice resulted in increased weight
      loss and more severe intestinal inflammation compared with wild type mice,
      indicating a protective role of Th17 cells in intestinal inflammation. Individual
      mice with lower levels of pIgR and intestinal-secreted IgA correlated with
      increased weight loss at the end of DSS administration. Collectively, our data
      reveal that microbiota-specific Th17 cells contribute to intestinal homeostasis
      by regulating intestinal pIgR expression and IgA secretion.

PMID- 22993209
TI  - Vascular bone tumors: a proposal of a classification based on
      clinicopathological, radiographic and genetic features.
AB  - The classification of vascular bone tumors remains challenging, with considerable
      morphological overlap spanning across benign to malignant categories. The vast
      majority of both benign and malignant vascular tumors are readily diagnosed based
      on their characteristic histological features, such as the formation of vascular
      spaces and the expression of endothelial markers. However, some vascular tumors
      have atypical histological features, such as a solid growth pattern, epithelioid
      change, or spindle cell morphology, which complicates their diagnosis.
      Pathologically, these tumors are remarkably similar, which makes differentiating
      them from each other very difficult. For this rare subset of vascular bone
      tumors, there remains considerable controversy with regard to the terminology and
      the classification that should be used. Moreover, one of the most confusing
      issues related to vascular bone tumors is the myriad of names that are used to
      describe them. Because the clinical behavior and, consequently, treatment and
      prognosis of vascular bone tumors can vary significantly, it is important to
      effectively and accurately distinguish them from each other. Upon review of the
      nomenclature and the characteristic clinicopathological, radiographic and genetic
      features of vascular bone tumors, we propose a classification scheme that
      includes hemangioma, hemangioendothelioma, angiosarcoma, and their epithelioid
      variants.

PMID- 22993210
TI  - MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA
      pathway.
AB  - Myosin- and Rab-interacting protein (MyRIP), which belongs to the protein kinase
      A (PKA)-anchoring family, is implicated in hormone secretion. However, its
      mechanism of action is not fully elucidated. Here we investigate the role of
      MyRIP in myosin Va (MyoVa)-dependent secretory granule (SG) transport and
      secretion in pancreatic beta cells. These cells solely express the brain isoform
      of MyoVa (BR-MyoVa), which is a key motor protein in SG transport. In vitro pull
      down, coimmunoprecipitation, and colocalization studies revealed that MyRIP does
      not interact with BR-MyoVa in glucose-stimulated pancreatic beta cells,
      suggesting that, contrary to previous notions, MyRIP does not link this motor
      protein to SGs. Glucose-stimulated insulin secretion is augmented by incretin
      hormones, which increase cAMP levels and leads to MyRIP phosphorylation, its
      interaction with BR-MyoVa, and phosphorylation of the BR-MyoVa receptor rabphilin
      3A (Rph-3A). Rph-3A phosphorylation on Ser-234 was inhibited by small interfering
      RNA knockdown of MyRIP, which also reduced cAMP-mediated hormone secretion.
      Demonstrating the importance of this phosphorylation, nonphosphorylatable and
      phosphomimic Rph-3A mutants significantly altered hormone release when PKA was
      activated. These data suggest that MyRIP only forms a functional protein complex
      with BR-MyoVa on SGs when cAMP is elevated and under this condition facilitates
      phosphorylation of SG-associated proteins, which in turn can enhance secretion.

PMID- 22993211
TI  - Role of the AAA protease Yme1 in folding of proteins in the intermembrane space
      of mitochondria.
AB  - The vast majority of mitochondrial proteins are synthesized in the cytosol and
      transported into the organelle in a largely, if not completely, unfolded state.
      The proper function of mitochondria thus depends on folding of several hundreds
      of proteins in the various subcompartments of the organelle. Whereas folding of
      proteins in the mitochondrial matrix is supported by members of several chaperone
      families, very little is known about folding of proteins in the intermembrane
      space (IMS). We targeted dihydrofolate reductase (DHFR) as a model substrate to
      the IMS of yeast mitochondria and analyzed its folding. DHFR can fold in this
      compartment, and its aggregation upon heat shock can be prevented in an ATP
      dependent manner. Yme1, an AAA (ATPases associated with diverse cellular
      activities) protease of the IMS, prevented aggregation of DHFR. Analysis of
      protein aggregates in mitochondria lacking Yme1 revealed the presence of a number
      of proteins involved in the establishment of mitochondrial ultrastructure, lipid
      metabolism, protein import, and respiratory growth. These findings explain the
      pleiotropic effects of deletion of YME1 and suggest an important role for Yme1 as
      a folding assistant, in addition to its proteolytic function, in the protein
      homeostasis of mitochondria.

PMID- 22993212
TI  - Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related
      to small G proteins.
AB  - Clathrin coat accessory proteins play key roles in transport mediated by clathrin
      coated vesicles. Yeast Irc6p and the related mammalian p34 are putative clathrin
      accessory proteins that interact with clathrin adaptor complexes. We present
      evidence that Irc6p functions in clathrin-mediated traffic between the trans
      Golgi network and endosomes, linking clathrin adaptor complex AP-1 and the Rab
      GTPase Ypt31p. The crystal structure of the Irc6p N-terminal domain revealed a G
      protein fold most related to small G proteins of the Rab and Arf families.
      However, Irc6p lacks G-protein signature motifs and high-affinity GTP binding.
      Also, mutant Irc6p lacking candidate GTP-binding residues retained function.
      Mammalian p34 rescued growth defects in irc6 cells, indicating functional
      conservation, and modeling predicted a similar N-terminal fold in p34. Irc6p and
      p34 also contain functionally conserved C-terminal regions. Irc6p/p34-related
      proteins with the same two-part architecture are encoded in genomes of species as
      diverse as plants and humans. Together these results define Irc6p/p34 as a novel
      type of conserved clathrin accessory protein and founding members of a new G
      protein-like family.

PMID- 22993213
TI  - Mitochondrial release of the NADH dehydrogenase Ndi1 induces apoptosis in yeast.
AB  - Saccharomyces cerevisiae NDI1 codes for the internal mitochondrial ubiquinone
      oxidoreductase, which transfers electrons from NADH to ubiquinone in the
      respiratory chain. Previously we found that Ndi1 is a yeast homologue of the
      protein apoptosis-inducing factor-homologous mitochondrion-associated inducer of
      death and displays potent proapoptotic activity. Here we show that S. cerevisiae
      NDI1 is involved in apoptosis induced by various stimuli tested, including
      H(2)O(2), Mn, and acetate acid, independent of Z-VAD-fmk (a caspase inhibitor)
      inhibition. Although Ndi1 also participates in respiration, its proapoptotic
      property is separable from the ubiquinone oxidoreductase activity. During
      apoptosis, the N-terminal of Ndi1 is cleaved off in the mitochondria, and this
      activated form then escapes out to execute its apoptotic function. The N-terminal
      cleavage appears to be essential for the manifestation of the full apoptotic
      activity, as the uncleaved form of Ndi1 exhibits much less growth-inhibitory
      activity. Our results thus indicate an important role of Ndi1 in the switch of
      life and death fates in yeast: during normal growth, Ndi1 assimilates electrons
      to the electron transport chain and initiates the respiration process to make
      ATP, whereas under stresses, it cleaves the toxicity-sequestering N-terminal cap,
      is released from the mitochondria, and becomes a cell killer.

PMID- 22993214
TI  - One-step purification of assembly-competent tubulin from diverse eukaryotic
      sources.
AB  - We have developed a protocol that allows rapid and efficient purification of
      native, active tubulin from a variety of species and tissue sources by affinity
      chromatography. The affinity matrix comprises a bacterially expressed,
      recombinant protein, the TOG1/2 domains from Saccharomyces cerevisiae Stu2,
      covalently coupled to a Sepharose support. The resin has a high capacity to
      specifically bind tubulin from clarified crude cell extracts, and, after washing,
      highly purified tubulin can be eluted under mild conditions. The eluted tubulin
      is fully functional and can be efficiently assembled into microtubules. The
      method eliminates the need to use heterologous systems for the study of
      microtubule-associated proteins and motor proteins, which has been a major issue
      in microtubule-related research.

PMID- 22993215
TI  - Science to practice: genetic engineering meets cell tracking--a promising
      approach for cell-based therapies?
AB  - Cell-based therapies are gaining increasing importance and have been evaluated in
      many settings, including cancer, Parkinson disease, myocardial repair, stroke,
      and diabetes. In this context, it is of major importance that the cells are
      implanted into an optimal tissue environment and, correspondingly, that they
      reach the diseased region. Intravenous cell injection often is the route of
      choice, particularly if the cells are expected to circulate in the blood for
      longer periods of time and are able to actively migrate to the diseased tissue.
      Unfortunately, often only a small percentage of intravenously injected cells
      reach the target area. Higher accumulation can be achieved if the cells are
      injected into an artery that feeds the diseased area. However, in this case, fast
      blood velocities and substantial sheer stress make it difficult for the cells to
      adhere. In the study by Gorelik and colleagues (1), genetic engineering was used
      to overcome this limitation. Glial precursor cells were transiently transfected
      with very late antigen-4 (VLA-4) binding to vascular cell adhesion molecule-1
      (VCAM-1), which is upregulated in inflamed endothelial cells. After labeling
      these cells with superparamagnetic iron oxide (SPIO) containing rhodamine,
      significantly increased binding to inflamed brain endothelial cells was shown and
      their homogeneous distribution over the inflamed brain tissue was convincingly
      demonstrated with magnetic resonance (MR) imaging and histologic examination. The
      authors concluded that transient transfection of SPIO-labeled cells with VLA-4 in
      combination with their arterial injection and the use of MR imaging monitoring
      may be an elegant way to increase the efficacy of cell-based treatments of
      inflammatory brain diseases.

PMID- 22993216
TI  - Through the Looking Glass revisited: the need for more meaning and less drama in
      the reporting of dose and dose reduction in CT.

PMID- 22993217
TI  - Controversies in cardiovascular MR imaging: T2-weighted imaging should not be
      used to delineate the area at risk in ischemic myocardial injury.
AB  - The use of T2-weighted MR imaging to delineate the area at risk and subsequently
      quantify myocardial salvage is problematic on many levels. The validation studies
      available thus far are inadequate. Unlike the data validating DE MR imaging, in
      which pathologic analysis has shown the precise shape and contour of the bright
      region exactly match the infarcted area, this level of validation does not exist
      for T2-weighted MR imaging. Technical advances have occurred, but image contrast
      between abnormal and normal regions remains limited, and in this situation,
      measured size differences between MR imaging data sets should not be
      overinterpreted. Moreover, with any T2 technique, there remains the key issue
      that there is no physiologic basis for the apparent T2 findings. Indeed, a
      homogeneously bright area at risk on T2-weighted MR images is incompatible with
      the known levels of edema that occur in infarcted and salvaged myocardium, and
      the finding that the lateral borders of T2 hyperintense regions frequently extend
      far beyond that of infarction is contrary to the wavefront phenomenon. Even if T2
      weighted MR imaging provided an accurate measure of myocardial edema, the level
      of edema within the area at risk is dependent on multiple variables, including
      infarct size, age, reperfusion status, reperfusion injury, and therapies that
      could have an antiedema effect. The area at risk is a coronary perfusion
      territory. There is a fundamental limitation with defining the area at risk by
      using a nonperfusion-based indicator that can vary with different postreperfusion
      therapies. There are several applications for T2 myocardial imaging, including
      differentiation of acute from chronic MI and identification of acute myocarditis.
      On the basis of the currently available data; however, we conclude that T2
      weighted MR imaging should not be used to delineate the area at risk in patients
      with ischemic myocardial injury.

PMID- 22993219
TI  - Chronic obstructive pulmonary disease: CT quantification of airways disease.
AB  - Chronic obstructive pulmonary disease (COPD) is an increasing cause of morbidity
      and mortality worldwide and results in substantial social and economic burdens.
      COPD is a heterogeneous disease with both extrapulmonary and pulmonary
      components. The pulmonary component is characterized by an airflow limitation
      that is not fully reversible. In the authors' opinion, none of the currently
      available classifications combining airflow limitation measurements with clinical
      parameters is sufficient to determine the prognosis and treatment of a particular
      patient with COPD. With regard to the causes of airflow limitation, CT can be
      used to quantify the two main contributions to COPD: emphysema, and small airways
      disease (a narrowing of the airways). CT quantification--with subsequent COPD
      phenotyping--can contribute to improved patient care, assessment of COPD
      progression, and identification of severe COPD with increasing risk of mortality.
      Small airways disease can be quantified through measurements reflecting
      morphology, quantification of obstruction, and changes in airways walls. This
      article details these three approaches and concludes with perspectives and
      directions for further research.

PMID- 22993218
TI  - Controversies in cardiovascular MR imaging: reasons why imaging myocardial T2 has
      clinical and pathophysiologic value in acute myocardial infarction.

PMID- 22993220
TI  - Pulmonary nodule size evaluation with chest tomosynthesis.
AB  - PURPOSE: To evaluate intra- and interobserver variability, as well as agreement
      for nodule size measurements on chest tomosynthesis and computed tomographic (CT)
      images. MATERIALS AND METHODS: The Regional Ethical Review Board approved this
      study, and all participants gave written informed consent. Thirty-six segmented
      nodules in 20 patients were included in the study. Eight observers measured the
      left-to-right, inferior-to-superior, and longest nodule diameters on chest
      tomosynthesis and CT images. Intra- and interobserver repeatability, as well as
      agreement between measurements on chest tomosynthesis and CT images, were
      assessed as recommended by Bland and Altman. RESULTS: The difference between the
      mean manual and the segmented diameter was -2.2 and -2.3 mm for left-to-right and
      -2.6 and -2.2 mm for the inferior-to-superior diameter for measurements on chest
      tomosynthesis and CT images, respectively. Intraobserver 95% limits of agreement
      (LOA) for the longest diameter ranged from a lower limit of -1.1 mm and an upper
      limit of 1.0 mm to -1.8 and 1.8 mm for chest tomosynthesis and from -0.6 and 0.9
      mm to -3.1 and 2.2 mm for axial CT. Interobserver 95% LOA ranged from -1.3 and
      1.5 mm to -2.0 and 2.1 mm for chest tomosynthesis and from -1.8 and 1.1 mm to 
      2.2 and 3.1 mm for axial CT. The 95% LOA concerning the mean of the observers'
      measurements of the longest diameter at chest tomosynthesis and axial CT were +/
      2.1 mm (mean measurement error, 0 mm). For the different observers, the 95% LOA
      between the modalities ranged from -2.2 and 1.6 mm to -3.2 and 2.8 mm.
      CONCLUSION: Measurements on chest tomosynthesis and CT images are comparable,
      because there is no evident bias between the modalities and the repeatability is
      similar. The LOA between measurements for the two modalities raise concern if
      measurements from chest tomosynthesis and CT were to be used interchangeably.

PMID- 22993221
TI  - Short-term mortality in acute pulmonary embolism: clot burden and signs of right
      heart dysfunction at CT pulmonary angiography.
AB  - PURPOSE: To assess the correlation between volumetric measurements of clot,
      semiquantitative clot burden indexes, and signs of right heart dysfunction at
      computed tomographic (CT) pulmonary angiography in patients with acute pulmonary
      embolism (PE) and to determine whether clot burden and signs of right heart
      dysfunction are associated with short-term mortality. MATERIALS AND METHODS: This
      retrospective study was institutional review board approved and HIPAA compliant.
      CT pulmonary angiographic studies (January 2007 through December 2007) with
      findings positive for PE were retrieved. Two readers evaluated signs of right
      heart dysfunction at CT pulmonary angiography, measured clot volume using a
      dedicated software program, and assessed clot burden using semiquantitative
      scores (Qanadli and Mastora). Spearman rank coefficient was used to investigate
      correlation between clot burden measures and signs of right heart dysfunction.
      Uni- and multivariate analyses were used to test association between CT pulmonary
      angiographic findings and short-term mortality. RESULTS: A total of 635 CT
      pulmonary angiographic studies from 635 patients (304 men, 331 women; mean age,
      59 years) were included; 39 (6%) patients died within 30 days. Clot volume was
      strongly correlated with Qanadli score (rho=0.841, P<.01) and Mastora score
      (rho=0.863, P<.01) and moderately correlated (rho=0.378, P<.01) with the ratio of
      right ventricle diameter to left ventricle diameter (RV/LV ratio). Among the
      pulmonary angiographic signs, only increase in RV/LV ratio (cut-off value, 1.0)
      was independently associated with short-term mortality in multivariate analysis.
      CONCLUSION: Clot volume strongly correlated with semiquantitative CT scores of
      clot burden, and greater clot volume was associated with higher incidence of
      right heart dilatation. Increase in RV/LV ratio was associated with short-term
      mortality; however, measures of clot burden were not.

PMID- 22993223
TI  - Case 186: Dysembrioplastic neuroepithelial tumor.

PMID- 22993224
TI  - Enhancement pattern of angiomyolipoma without visible fat versus that of renal
      cell carcinoma.

PMID- 22993225
TI  - Imaging-guided breast cancer ablation.

PMID- 22993226
TI  - Low serum levels of vitamin D in idiopathic inflammatory myopathies.
AB  - OBJECTIVES: To evaluate serum levels of 25(OH) vitamin D in patients with
      idiopathic inflammatory myopathies (IIM) (polymyositis (PM), dermatomyosistis
      (DM), inclusion body myositis (IBM) and juvenile DM (JDM)) and to compare these
      with healthy controls. METHODS: Serum samples from 149 patients with IIM and 290
      healthy controls matched for gender and the month of blood sampling were analysed
      for 25(OH) vitamin D. ORs for vitamin D classes with 95% CI were calculated using
      a matched (conditional) logistic regression model. Groups were compared by the
      Kruskal-Wallis test and p values <0.05 were considered significant. RESULTS:
      Patients with IIM had significantly lower serum levels of 25(OH) vitamin D than
      healthy controls (median 39 (10-168) nmol/l vs 68 (19-197) nmol/l; p=0.0001).
      There was no significant difference in vitamin D levels between the myositis
      subgroups. When vitamin D levels were subclassified into deficient (<50 nmol/l),
      insufficient (50-74 nmol/l) and normal (>=75 nmol/l), most of the patients with
      PM (68%), DM (65%) and IBM (53%) had deficient levels compared with only 60 (21%)
      healthy individuals. In patients with IIM the OR for deficient versus normal was
      17.7 (95% CI 8.1 to 38.6) and the OR for insufficient versus normal was 2.4 (95%
      CI 1.2 to 4.7). CONCLUSIONS: Low serum levels of vitamin D were found in most
      patients with IIM and may confer a risk factor for developing adult myositis,
      similar to some other autoimmune diseases.

PMID- 22993227
TI  - Increased IL-17A expression in temporal artery lesions is a predictor of
      sustained response to glucocorticoid treatment in patients with giant-cell
      arteritis.
AB  - BACKGROUND: Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in
      chronic inflammatory and autoimmune diseases. OBJECTIVE: To investigate IL-17A
      expression in temporal artery lesions from patients with giant-cell arteritis
      (GCA), and its relationship with disease outcome. METHODS: Fifty-seven patients
      with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.5
      years (52-464 weeks). Relapses, time (weeks) required to achieve a maintenance
      prednisone dose <10 mg/day, and time (weeks) to complete prednisone withdrawal
      were prospectively recorded. IL-17A mRNA was measured by real-time quantitative
      RT-PCR in temporal arteries from all patients and 19 controls. IL-17 protein
      expression was assessed by immunohistochemistry/immunofluorescence. RESULTS: IL
      17A expression was significantly increased in temporal artery samples from GCA
      patients compared with controls (6.22+/-8.61 vs 2.50+/-3.9 relative units,
      p=0.016). Surprisingly, patients with strong IL-17A expression tended to
      experience less relapses, and required significantly shorter treatment periods
      (median 25 vs 44 weeks to achieve <10 mg prednisone/day, p=0.0079). There was no
      correlation between IL-17A and RORc or RORalpha expression suggesting that these
      transcription factors may not exclusively reflect Th17 differentiation, and that
      cells other than Th17 cells might contribute to IL-17 expression in active
      patients. Accordingly, FoxP3(+)IL-17A(+) cells were identified in lesions by
      confocal microscopy and were dramatically reduced in specimens from treated
      patients. CONCLUSIONS: IL-17A expression is increased in GCA lesions, and is a
      predictor of response to glucocorticoid treatment. The contribution of FoxP3+
      cells to IL-17A production in untreated patients suggests that induced-Tregs may
      facilitate disease remission when proinflammatory cytokine production is
      downregulated by glucocorticosteroids.

PMID- 22993228
TI  - Novel genetic variants associated with lumbar disc degeneration in northern
      Europeans: a meta-analysis of 4600 subjects.
AB  - OBJECTIVE: Lumbar disc degeneration (LDD) is an important cause of low back pain,
      which is a common and costly problem. LDD is characterised by disc space
      narrowing and osteophyte growth at the circumference of the disc. To date, the
      agnostic search of the genome by genome-wide association (GWA) to identify common
      variants associated with LDD has not been fruitful. This study is the first GWA
      meta-analysis of LDD. METHODS: We have developed a continuous trait based on disc
      space narrowing and osteophytes growth which is measurable on all forms of
      imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five
      cohorts of Northern European extraction each having GWA data imputed to HapMap
      V.2. RESULTS: This study of 4600 individuals identified four single nucleotide
      polymorphisms with p<5*10(-8), the threshold set for genome-wide significance. We
      identified a variant in the PARK2 gene (p=2.8*10(-8)) associated with LDD.
      Differential methylation at one CpG island of the PARK2 promoter was observed in
      a small subset of subjects (beta=8.74*10(-4), p=0.006). CONCLUSIONS: LDD accounts
      for a considerable proportion of low back pain and the pathogenesis of LDD is
      poorly understood. This work provides evidence of association of the PARK2 gene
      and suggests that methylation of the PARK2 promoter may influence degeneration of
      the intervertebral disc. This gene has not previously been considered a candidate
      in LDD and further functional work is needed on this hitherto unsuspected
      pathway.

PMID- 22993229
TI  - The structural basis of MRI bone erosions: an assessment by microCT.
AB  - OBJECTIVE: To determine whether erosions appearing in MRI in patients with
      rheumatoid arthritis (RA) represent true erosions. METHODS: 50 RA patients
      received 1.5 T MRI and microCT (MUCT) of the dominant hand. Erosion counts were
      assessed in coronal T1 weighted MRI sections and in coronal as well as axial MUCT
      sections of the metacarpophalangeal (MCP) joints II-IV. Extent of erosions was
      assessed by RA MRI Score (RAMRIS) erosion score (MRI) and by three-dimensional
      assessment of erosion volume (MUCT). RESULTS: 111 of the 600 evaluated joint
      regions showed erosions in the MRI and 137 in the MUCT. In only 28 regions false
      negative lesions (MUCT positive, MRI negative) were found, all of which were very
      small lesions with a volume of less than 10 mm(3). Only two results were false
      positive (MUCT negative, MRI positive). RAMRIS erosion scores were strongly
      correlated to erosion volumes in the MUCT (Pearson's r=0.514, p<0.001). Mean
      RAMRIS erosion scores were below 1 with erosion volumes up to 1.5 mm(3), below 2
      with erosion volumes up to 20 mm(3) and over 2 with volumes of more than 20
      mm(3). DISCUSSION: MRI erosions are generally based on true cortical breaks as
      shown by MUCT. MRI is sensitive to detect bone erosions and only very small
      lesions escape detection. Moreover, RAMRIS erosion scores are closely linked to
      the absolute size of bone erosions in the MUCT.

PMID- 22993230
TI  - Functional characterization of thioesterase superfamily member 1/Acyl-CoA
      thioesterase 11: implications for metabolic regulation.
AB  - Thioesterase superfamily member 1 (Them1; synonyms acyl-CoA thioesterase 11 and
      StarD14) is highly expressed in brown adipose tissue and limits energy
      expenditure in mice. Them1 is a putative fatty acyl-CoA thioesterase that
      comprises tandem hot dog-fold thioesterase domains and a lipid-binding C-terminal
      steroidogenic acute regulatory protein-related lipid transfer (START) domain. To
      better define its role in metabolic regulation, this study examined the
      biochemical and enzymatic properties of Them1. Purified recombinant Them1
      dimerized in solution to form an active fatty acyl-CoA thioesterase. Dimerization
      was induced by fatty acyl-CoAs, coenzyme A (CoASH), ATP, and ADP. Them1
      hydrolyzed a range of fatty acyl-CoAs but exhibited a relative preference for
      long-chain molecular species. Thioesterase activity varied inversely with
      temperature, was stimulated by ATP, and was inhibited by ADP and CoASH. Whereas
      the thioesterase domains of Them1 alone were sufficient to yield active
      recombinant protein, the START domain was required for optimal enzyme activity.
      An analysis of subcellular fractions from mouse brown adipose tissue and liver
      revealed that Them1 contributes principally to the fatty acyl-CoA thioesterase
      activity of microsomes and nuclei. These findings suggest that under biological
      conditions, Them1 functions as a lipid-regulated fatty acyl-CoA thioesterase that
      could be targeted for the management of metabolic disorders.

PMID- 22993231
TI  - Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing
      and alters chylomicron production in Apobec1 -/- mice.
AB  - Intestinal apolipoprotein B (apoB) mRNA undergoes C-to-U editing, mediated by the
      catalytic deaminase apobec-1, which results in translation of apoB48. Apobec1(-/
      ) mice produce only apoB100 and secrete larger chylomicron particles than those
      observed in wild-type (WT) mice. Here we show that transgenic rescue of
      intestinal apobec-1 expression (Apobec1(Int/O)) restores C-to-U RNA editing of
      apoB mRNA in vivo, including the canonical site at position 6666 and also at
      approximately 20 other newly identified downstream sites present in WT mice. The
      small intestine of Apobec1(Int/O) mice produces only apoB48, and the liver
      produces only apoB100. Serum chylomicron particles were smaller in Apobec1(Int/O)
      mice compared with those from Apobec1(-/-) mice, and the predominant fraction of
      serum apoB48 in Apobec1(Int/O) mice migrated in lipoproteins smaller than
      chylomicrons, even when these mice were fed a high-fat diet. Because apoB48
      arises exclusively from the intestine in Apobec1(Int/O) mice and intestinal
      apoB48 synthesis and secretion rates were comparable to WT mice, we were able to
      infer the major sites of origin of serum apoB48 in WT mice. Our findings imply
      that less than 25% of serum apoB48 in WT mice arises from the intestine, with the
      majority originating from the liver.

PMID- 22993232
TI  - Adiposoft: automated software for the analysis of white adipose tissue
      cellularity in histological sections.
AB  - The accurate estimation of the number and size of cells provides relevant
      information on the kinetics of growth and the physiological status of a given
      tissue or organ. Here, we present Adiposoft, a fully automated open-source
      software for the analysis of white adipose tissue cellularity in histological
      sections. First, we describe the sequence of image analysis routines implemented
      by the program. Then, we evaluate our software by comparing it with other adipose
      tissue quantification methods, namely, with the manual analysis of cells in
      histological sections (used as gold standard) and with the automated analysis of
      cells in suspension, the most commonly used method. Our results show significant
      concordance between Adiposoft and the other two methods. We also demonstrate the
      ability of the proposed method to distinguish the cellular composition of three
      different rat fat depots. Moreover, we found high correlation and low
      disagreement between Adiposoft and the manual delineation of cells. We conclude
      that Adiposoft provides accurate results while considerably reducing the amount
      of time and effort required for the analysis.

PMID- 22993233
TI  - Barriers to retention in care as perceived by persons living with HIV in rural
      Ethiopia: focus group results and recommended strategies.
AB  - Inability to retain HIV-infected patients in care undermines the benefits of
      starting millions in low-income countries on antiretroviral therapy (ART). In a
      hospital HIV clinic in rural southern Ethiopia, we conducted focus groups of HIV
      infected men and women to learn more about experiences with and barriers to
      attending clinic appointments. Respondents reported multiple barriers, including
      those that were patient related (eg, misunderstandings about ART, mistaken belief
      in AIDS cures, and drug/alcohol use), clinic related (eg, negative provider
      interactions, lack of familiarity with patients' medical situation, and
      overcrowding), medication related (eg, side effects), social (eg, stigma and
      discrimination and lack of support), and situational/resource related (eg,
      distance to clinic, lack of funds, competing domestic/work priorities, and lack
      of food). Based on the lessons learned from these focus groups, we implemented a
      community intervention to improve retention, using trained community support
      workers who provide patient education, counseling, social support, problem
      solving assistance, needed referrals, and improved communication/linkage to the
      patients' HIV clinic.

PMID- 22993234
TI  - Perceived family support and depression among people living with HIV/AIDS in the
      Kathmandu Valley, Nepal.
AB  - BACKGROUND: Depression is emerging as a highly prevalent psychiatric condition
      among people living with HIV/AIDS (PLWHA). Perceived family support (PFS) buffers
      depression among chronic disease patients. However, a similar relationship among
      PLWHA is unexplored. OBJECTIVE: To examine the relationship between PFS and
      depression among PLWHA in the Kathmandu Valley, Nepal. METHODS: In this cross
      sectional study, depression was measured by Beck Depression Inventory Ia.
      Perceived family support was measured by Nepali Family Support and Difficulties
      Scale. The status of depression was compared between 208 PLWHA and 208 HIV
      negative participants. The relationship between PFS and depression was examined
      only among PLWHA. RESULTS: Among each of the 208 participants, the number of
      depressed PLWHA (n = 61,29.3%) was higher than that of HIV-negative participants
      (n = 13,6.2%; P < .001). Perceived family support had a negative association with
      depression in PLWHA (adjusted odds ratio [AOR] = 0.20, 95% confidence interval
      [CI] = 0.08-0.53). CONCLUSION: In Nepal, PLWHA display a higher level of
      depression than HIV-negative people, and a lower level of PFS is associated with
      depression among PLWHA. Improved family support might be helpful in reducing
      depression among Nepalese PLWHA.

PMID- 22993235
TI  - Transcriptome analysis of foraminiferan Elphidium margaritaceum questions the
      role of gene transfer in kleptoplastidy.
AB  - Foraminifera from the genus Elphidium are heterotrophic protists that graze on
      diatoms and sequester chloroplasts from their algal preys, while digesting the
      rest of the diatom cell. During that process, known as kleptoplastidy, the
      acquired plastids remain active inside the foraminiferan cell for several months.
      As most of the genes required to sustain the activity of the chloroplasts are
      encoded in the diatom nucleus, it is unknown how the host cell can maintain the
      photosynthetic activity without this information. It has been proposed that
      maintenance of kleptoplastids could be explained by horizontal gene transfer
      (HGT). To test this hypothesis we obtained 17,125 EST sequences of Elphidium
      margaritaceum, and we screened this data set for diatom nuclear-encoded proteins
      having a function in photosynthetic activity or plastid maintenance. Our analyses
      show no evidence for the presence of such transcriptionally active genes and
      suggest that HGT hypothesis alone cannot explain the chloroplast's longevity in
      Elphidium.

PMID- 22993236
TI  - Evidence for compensatory evolution of ribosomal proteins in response to rapid
      divergence of mitochondrial rRNA.
AB  - Rapid evolution of mitochondrial DNA (mtDNA) places intrinsic selective pressures
      on many nuclear genes involved in mitochondrial functions. Mitochondrial
      ribosomes, for example, are composed of mtDNA-encoded ribosomal RNAs (rRNAs) and
      a set of more than 60 nuclear-encoded ribosomal proteins (mRP) distinct from the
      cytosolic RPs (cRP). We hypothesized that the rapid divergence of mt-rRNA would
      result in rapid evolution of mRPs relative to cRPs, which respond to slowly
      evolving nuclear-encoded rRNA. In comparisons of rates of nonsynonymous and
      synonymous substitutions between a pair of divergent populations of the copepod
      Tigriopus californicus, we found that mRPs showed elevated levels of amino acid
      changes relative to cRPs. This pattern was equally strong at the interspecific
      level, between three pairs of sister species (Nasonia vitripennis vs. N.
      longicornis, Drosophila melanogaster vs. D. simulans, and Saccharomyces cerevisae
      vs. S. paradoxus). This high rate of mRP evolution may result in intergenomic
      incompatibilities between taxonomic lineages, and such incompatibilities could
      lead to dysfunction of mitochondrial ribosomes and the loss of fitness observed
      among interpopulation hybrids in T. californicus and interspecific hybrids in
      other species.

PMID- 22993238
TI  - Resolving the phylogeny of lizards and snakes (Squamata) with extensive sampling
      of genes and species.
AB  - Squamate reptiles (lizards and snakes) are one of the most diverse groups of
      terrestrial vertebrates. Recent molecular analyses have suggested a very
      different squamate phylogeny relative to morphological hypotheses, but many
      aspects remain uncertain from molecular data. Here, we analyse higher-level
      squamate phylogeny with a molecular dataset of unprecedented size, including 161
      squamate species for up to 44 nuclear genes each (33 717 base pairs), using both
      concatenated and species-tree methods for the first time. Our results strongly
      resolve most squamate relationships and reveal some surprising results. In
      contrast to most other recent studies, we find that dibamids and gekkotans are
      together the sister group to all other squamates. Remarkably, we find that the
      distinctive scolecophidians (blind snakes) are paraphyletic with respect to other
      snakes, suggesting that snakes were primitively burrowers and subsequently re
      invaded surface habitats. Finally, we find that some clades remain poorly
      supported, despite our extensive data. Our analyses show that weakly supported
      clades are associated with relatively short branches for which individual genes
      often show conflicting relationships. These latter results have important
      implications for all studies that attempt to resolve phylogenies with large-scale
      phylogenomic datasets.

PMID- 22993237
TI  - Inference on population histories by approximating infinite alleles diffusion.
AB  - Reconstruction of the past is an important task of evolutionary biology. It takes
      place at different points in a hierarchy of molecular variation, including genes,
      individuals, populations, and species. Statistical inference about population
      histories has recently received considerable attention, following the development
      of computational tools to provide tractable approaches to this very challenging
      problem. Here, we introduce a likelihood-based approach which generalizes a
      recently developed model for random fluctuations in allele frequencies based on
      an approximation to the neutral Wright-Fisher diffusion. Our new framework
      approximates the infinite alleles Wright-Fisher model and uses an implementation
      with an adaptive Markov chain Monte Carlo algorithm. The method is especially
      well suited to data sets harboring large population samples and relatively few
      loci for which other likelihood-based models are currently computationally
      intractable. Using our model, we reconstruct the global population history of a
      major human pathogen, Streptococcus pneumoniae. The results illustrate the
      potential to reach important biological insights to an evolutionary process by a
      population genetics approach, which can appropriately accommodate very large
      population samples.

PMID- 22993239
TI  - Cone monochromacy and visual pigment spectral tuning in wobbegong sharks.
AB  - Much is known regarding the evolution of colour vision in nearly every vertebrate
      class, with the notable exception of the elasmobranchs. While multiple spectrally
      distinct cone types are found in some rays, sharks appear to possess only a
      single class of cone and, therefore, may be colour blind. In this study, the
      visual opsin genes of two wobbegong species, Orectolobus maculatus and
      Orectolobus ornatus, were isolated to verify the molecular basis of their
      monochromacy. In both species, only two opsin genes are present, RH1 (rod) and
      LWS (cone), which provide further evidence to support the concept that sharks
      possess only a single cone type. Examination of the coding sequences revealed
      substitutions that account for interspecific variation in the photopigment
      absorbance spectra, which may reflect the difference in visual ecology between
      these species.

PMID- 22993240
TI  - Maternal predator-exposure has lifelong consequences for offspring learning in
      threespined sticklebacks.
AB  - Learning is an important form of phenotypic plasticity that allows organisms to
      adjust their behaviour to the environment. An individual's learning performance
      can be affected by its mother's environment. For example, mothers exposed to
      stressors, such as restraint and forced swimming, often produce offspring with
      impaired learning performance. However, it is unclear whether there are maternal
      effects on offspring learning when mothers are exposed to ecologically relevant
      stressors, such as predation risk. Here, we examined whether maternal predator
      exposure affects adult offsprings' learning of a discrimination task in
      threespined sticklebacks (Gasterosteus aculeatus). Mothers were either repeatedly
      chased by a model predator (predator-exposed) or not (unexposed) while producing
      eggs. Performance of adult offspring from predator-exposed and unexposed mothers
      was assessed in a discrimination task that paired a particular coloured chamber
      with a food reward. Following training, all offspring learned the colour
      association, but offspring of predator-exposed mothers located the food reward
      more slowly than offspring of unexposed mothers. This pattern was not driven by
      initial differences in exploratory behaviour. These results demonstrate that an
      ecologically relevant stressor (predation risk) can induce maternal effects on
      offspring learning, and perhaps behavioural plasticity more generally, that last
      into adulthood.

PMID- 22993241
TI  - Lung collapse in the diving sea lion: hold the nitrogen and save the oxygen.
AB  - Lung collapse is considered the primary mechanism that limits nitrogen absorption
      and decreases the risk of decompression sickness in deep-diving marine mammals.
      Continuous arterial partial pressure of oxygen   profiles in a free-diving female
      California sea lion (Zalophus californianus) revealed that (i) depth of lung
      collapse was near 225 m as evidenced by abrupt changes in   during descent and
      ascent, (ii) depth of lung collapse was positively related to maximum dive depth,
      suggesting that the sea lion increased inhaled air volume in deeper dives and
      (iii) lung collapse at depth preserved a pulmonary oxygen reservoir that
      supplemented blood oxygen during ascent so that mean end-of-dive arterial   was
      74 +/- 17 mmHg (greater than 85% haemoglobin saturation). Such information is
      critical to the understanding and the modelling of both nitrogen and oxygen
      transport in diving marine mammals.

PMID- 22993242
TI  - Manual aspiration thrombectomy for cerebral venous sinus thrombosis.
AB  - BACKGROUND: Hydration and anticoagulation are the standard of care for cerebral
      venous sinus thrombosis (CVST) but some patients remain refractory to medical
      management and warrant more aggressive therapy. Here we present the technique of
      endovascular transvenous manual aspiration thrombectomy (MAT) in six patients.
      OBJECTIVE: Present an alternative technique for endovascular transvenous
      thrombectomy in a series of CVST patients. METHODS: We reviewed the records of
      six patients with medically refractory CVST. Transvenous access via the femoral
      vein was used to advance an aspiration catheter of varying internal diameter
      (0.044, 0.054, 0.057, 0.070, 0.072) up to and through the thrombus. Tissue
      plasminogen activator was administered in select cases. Manual aspiration with a
      20 ml syringe applied to the catheter hub was applied as the catheter was slowly
      retracted. Presentation, technique, and outcome were evaluated. RESULTS: Clinical
      presentation included vomiting, dehydration, mental status changes, headaches,
      and acute motor deficits. On imaging, four of the six patients had hemorrhage,
      edema, and mass effect present before treatment, while two had edema only. All
      patients demonstrated continued deterioration despite early and aggressive
      medical anticoagulation therapy, warranting aggressive intervention. Aspiration
      of the superior sagittal sinus, transverse sinuses, straight sinus, sigmoid
      sinus, and internal jugular vein were performed in this series. There were no
      procedural complications. Revascularization was achieved in all instances. A
      modified Rankin Scale score of 1-3 was attained in 5/6 patients, while one
      patient died. CONCLUSIONS: In this series, transvenous MAT was a safe, simple,
      and effective revascularization technique to treat patients with CVST who
      remained refractory to medical management.

PMID- 22993243
TI  - Initial experience with Penumbra Coil 400 versus standard coils in embolization
      of cerebral aneurysms: a retrospective review.
AB  - BACKGROUND AND PURPOSE: The Penumbra Coil 400 System (PC 400) is the newly
      introduced platinum coil system designed specifically to enhance filling
      efficiency by increasing coil diameter. Our goal was to study the packing and
      treatment advantage of the PC 400's unique geometric configuration compared with
      conventional coils (controls). MATERIALS AND METHODS: 16 aneurysms embolized with
      the PC 400 in 2011 were compared with 79 equally matched aneurysms embolized with
      conventional coils from 2004 to 2011. Primary outcomes assessed were acute
      packing density, embolization time, and the number of coils required for aneurysm
      occlusion. RESULTS: Aneurysm embolization with the PC 400 achieved a higher
      packing density (36.8% vs 28.1%; p<0.005) and with fewer coils (an average of 3.9
      vs 6.1 coils per aneurysm; p<0.05). In addition, the total procedural time for
      the subjects treated with the PC 400 was significantly less (45.7 vs 64.1 min;
      p<0.05). There were no procedural complications associated with the PC 400.
      CONCLUSIONS: Compared with conventional coils, the PC 400 is more efficient in
      the embolization of cerebral aneurysms, achieving greater packing density with
      fewer coils and less time without compromising safety.

PMID- 22993244
TI  - Efficacy of intra-arterial therapy in the elderly requires further study.

PMID- 22993245
TI  - Double-barrel extracranial-intracranial bypass surgery followed by endovascular
      carotid artery occlusion in a patient with an extracranial giant internal carotid
      artery aneurysm due to Ehlers-Danlos syndrome.
AB  - OBJECTIVE: In this case report we describe a successful interdisciplinary
      approach (including flow redirection and endovascular occlusion) applied to a
      patient with a continuously growing extracranial giant aneurysm of the right
      internal carotid artery (ICA) due to known Ehlers-Danlos syndrome. CASE
      PRESENTATION: A 42-year-old man with a continuously growing extracranial giant
      aneurysm of the right ICA sought treatment after failed surgery of a similar
      lesion of the left ICA. A multidisciplinary consultation was held at the end of
      2008. TREATMENT STRATEGY: The treatment strategy consisted of flow redirection in
      order to secure sufficient cerebral perfusion prior to surgical trapping of the
      carotid aneurysm. Flow redirection was achieved by placement of a double-barrel
      extracranial-intracranial bypass. Subsequent surgical trapping failed due to the
      extreme size of the aneurysm, making certain identification of surrounding
      structures impossible. The aneurysm was then successfully occluded by
      neuroradiological intervention. In a further procedure, a large intra-aneurysmal
      hematoma was surgically removed to reduce the remaining bulging aneurysm sac.
      CONCLUSIONS: This case report describes a successful interdisciplinary approach
      for the treatment of a rare giant extracranial ICA aneurysm in a patient with
      Ehlers-Danlos syndrome. Treatment options for this type are few and carry high
      risks. Flow redirection via extracranial-intracranial bypass followed by
      endovascular occlusion appears to be a good treatment approach.

PMID- 22993246
TI  - Macroscale adhesion of gecko setae reflects nanoscale differences in subsurface
      composition.
AB  - Surface energies are commonly used to determine the adhesion forces between
      materials. However, the component of surface energy derived from long-range
      forces, such as van der Waals forces, depends on the material's structure below
      the outermost atomic layers. Previous theoretical results and indirect
      experimental evidence suggest that the van der Waals energies of subsurface
      layers will influence interfacial adhesion forces. We discovered that nanometre
      scale differences in the oxide layer thickness of silicon wafers result in
      significant macroscale differences in the adhesion of isolated gecko setal
      arrays. Si/SiO(2) bilayer materials exhibited stronger adhesion when the SiO(2)
      layer is thin (approx. 2 nm). To further explore how layered materials influence
      adhesion, we functionalized similar substrates with an octadecyltrichlorosilane
      monolayer and again identified a significant influence of the SiO(2) layer
      thickness on adhesion. Our theoretical calculations describe how variation in the
      SiO(2) layer thickness produces differences in the van der Waals interaction
      potential, and these differences are reflected in the adhesion mechanics. Setal
      arrays used as tribological probes provide the first empirical evidence that the
      'subsurface energy' of inhomogeneous materials influences the macroscopic surface
      forces.

PMID- 22993247
TI  - The dynamics of adapting, unregulated populations and a modified fundamental
      theorem.
AB  - A population in a novel environment will accumulate adaptive mutations over time,
      and the dynamics of this process depend on the underlying fitness landscape: the
      fitness of and mutational distance between possible genotypes in the population.
      Despite its fundamental importance for understanding the evolution of a
      population, inferring this landscape from empirical data has been problematic. We
      develop a theoretical framework to describe the adaptation of a stochastic,
      asexual, unregulated, polymorphic population undergoing beneficial, neutral and
      deleterious mutations on a correlated fitness landscape. We generate quantitative
      predictions for the change in the mean fitness and within-population variance in
      fitness over time, and find a simple, analytical relationship between the
      distribution of fitness effects arising from a single mutation, and the change in
      mean population fitness over time: a variant of Fisher's 'fundamental theorem'
      which explicitly depends on the form of the landscape. Our framework can
      therefore be thought of in three ways: (i) as a set of theoretical predictions
      for adaptation in an exponentially growing phase, with applications in pathogen
      populations, tumours or other unregulated populations; (ii) as an analytically
      tractable problem to potentially guide theoretical analysis of regulated
      populations; and (iii) as a basis for developing empirical methods to infer
      general features of a fitness landscape.

PMID- 22993249
TI  - Generating a random sequence of left and right eyes for ophthalmic research.

PMID- 22993250
TI  - Profiles of macular pigment optical density and their changes following
      supplemental lutein and zeaxannthin.

PMID- 22993252
TI  - Predicting evolutionary responses to selection on polyandry in the wild: additive
      genetic covariances with female extra-pair reproduction.
AB  - The evolutionary forces that underlie polyandry, including extra-pair
      reproduction (EPR) by socially monogamous females, remain unclear. Selection on
      EPR and resulting evolution have rarely been explicitly estimated or predicted in
      wild populations, and evolutionary predictions are vulnerable to bias due to
      environmental covariances and correlated selection through unmeasured traits.
      However, evolutionary responses to (correlated) selection on any trait can be
      directly predicted as additive genetic covariances (cov(A)) with appropriate
      components of relative fitness. I used comprehensive life-history, paternity and
      pedigree data from song sparrows (Melospiza melodia) to estimate cov(A) between a
      female's liability to produce extra-pair offspring and two specific fitness
      components: relative annual reproductive success (ARS) and survival to
      recruitment. All three traits showed non-zero additive genetic variance.
      Estimates of cov(A) were positive, predicting evolution towards increased EPR,
      but 95% credible intervals overlapped zero. There was therefore no conclusive
      prediction of evolutionary change in EPR due to (correlated) selection through
      female ARS or recruitment. Negative environmental covariance between EPR and ARS
      would have impeded evolutionary prediction from phenotypic selection
      differentials. These analyses demonstrate an explicit quantitative genetic
      approach to predicting evolutionary responses to components of (correlated)
      selection on EPR that should be unbiased by environmental covariances and
      unmeasured traits.

PMID- 22993248
TI  - Regulation of endothelial MAPK/ERK signalling and capillary morphogenesis by low
      amplitude electric field.
AB  - Low-amplitude electric field (EF) is an important component of wound-healing
      response and can promote vascular tissue repair; however, the mechanisms of
      action on endothelium remain unclear. We hypothesized that physiological
      amplitude EF regulates angiogenic response of microvascular endothelial cells via
      activation of the mitogen-activated protein kinase/extracellular signal-regulated
      kinase (MAPK/ERK) pathway. A custom set-up allowed non-thermal application of EF
      of high (7.5 GHz) and low (60 Hz) frequency. Cell responses following up to 24 h
      of EF exposure, including proliferation and apoptosis, capillary morphogenesis,
      vascular endothelial growth factor (VEGF) expression and MAPK pathways activation
      were quantified. A db/db mouse model of diabetic wound healing was used for in
      vivo validation. High-frequency EF enhanced capillary morphogenesis, VEGF
      release, MEK-cRaf complex formation, MEK and ERK phosphorylation, whereas no
      MAPK/JNK and MAPK/p38 pathways activation was observed. The endothelial response
      to EF did not require VEGF binding to VEGFR2 receptor. EF-induced MEK
      phosphorylation was reversed in the presence of MEK and Ca(2+) inhibitors,
      reduced by endothelial nitric oxide synthase inhibition, and did not depend on
      PI3K pathway activation. The results provide evidence for a novel intracellular
      mechanism for EF regulation of endothelial angiogenic response via frequency
      sensitive MAPK/ERK pathway activation, with important implications for EF-based
      therapies for vascular tissue regeneration.

PMID- 22993253
TI  - Sexual dichromatism in frogs: natural selection, sexual selection and unexpected
      diversity.
AB  - Sexual dichromatism, a form of sexual dimorphism in which males and females
      differ in colour, is widespread in animals but has been predominantly studied in
      birds, fishes and butterflies. Moreover, although there are several proposed
      evolutionary mechanisms for sexual dichromatism in vertebrates, few studies have
      examined this phenomenon outside the context of sexual selection. Here, we
      describe unexpectedly high diversity of sexual dichromatism in frogs and create a
      comparative framework to guide future analyses of the evolution of these sexual
      colour differences. We review what is known about evolution of colour dimorphism
      in frogs, highlight alternative mechanisms that may contribute to the evolution
      of sexual colour differences, and compare them to mechanisms active in other
      major groups of vertebrates. In frogs, sexual dichromatism can be dynamic
      (temporary colour change in males) or ontogenetic (permanent colour change in
      males or females). The degree and the duration of sexual colour differences vary
      greatly across lineages, and we do not detect phylogenetic signal in the
      distribution of this trait, therefore frogs provide an opportunity to investigate
      the roles of natural and sexual selection across multiple independent derivations
      of sexual dichromatism.

PMID- 22993254
TI  - The limited usefulness of models based on recollection and familiarity.
AB  - A recent report concluded that magnetoencephalographic signals of neural activity
      associated with memory based on the recollection process are independent from
      signals associated with memory based on the familiarity process. These data can
      be interpreted equally well, however, as indications of memory aggregated from
      both processes and showing that signals associated with high-confidence
      recognition are dissociable from signals associated with low-confidence
      recognition. The usefulness of interpreting neural data according to
      psychological models based on recollection and familiarity is discussed.

PMID- 22993255
TI  - Looking at the task in hand impairs motor learning.
AB  - "Visual capture" is the term used to describe vision being afforded a higher
      weighting than other sensory information. Visual capture can produce powerful
      illusory effects with individuals misjudging the size and position of their
      hands. The advent of laparoscopic surgical techniques raises the question of
      whether visual capture can interfere with an individual's rate of motor learning.
      We compared adaptation to distorted visual feedback in two groups: the Direct
      group appeared to have the advantage of directly viewing the input device, while
      the Indirect group used the same input device but viewed their movements on a
      remote screen. Counterintuitively, the Indirect group adapted more readily to
      distorted feedback and showed enhanced performance. The results show that visual
      capture impairs adaptation to distorted visual feedback, suggesting that surgeons
      need to avoid viewing their hands when learning laparoscopic techniques.

PMID- 22993256
TI  - Arcuate Src activation-induced phosphorylation of NR2B NMDA subunit contributes
      to inflammatory pain in rats.
AB  - The tyrosine kinases of Src family play an important role in the central
      sensitization following peripheral inflammation. However, whether the Src family
      in the arcuate nucleus (ARC) of mediobasal hypothalamus is involved in central
      sensitization remains unknown. The aim of this study was to investigate the role
      and mechanisms of tyrosine kinases of Src family in N-methyl-d-aspartate (NMDA)
      receptor activity in the ARC following peripheral inflammation. Peripheral
      inflammation was induced by unilateral injection of complete Freund's adjuvant
      (CFA) into rat hindpaw. The neuronal activities of the ARC were recorded using
      electrophysiological field recording from the in vitro mediobasal hypothalamic
      slices from control and CFA rats. Expression of total and phosphorylated Src and
      NR2B subunit protein was analyzed by Western blot and immuoprecipitation. Our
      results showed that CFA injection resulted in an increase in mechanical and
      thermal sensitivity, which was partially blocked by neonatal monosodium glutamate
      treatment. CFA injection also enhanced spontaneous firings of ARC neurons, which
      were reversed by the NMDA receptor NR2B subunit specific antagonist Ro25-6981 and
      by PP2, an Src family tyrosine kinase inhibitor. In addition, peripheral
      inflammation enhanced Src phosphorylation and NMDA receptor NR2B subunit
      phosphorylation without alteration of total NR2B subunit expression in the ARC.
      Peripheral inflammation also increased the association of NR2B protein with p-Src
      protein in the ARC. Administration of PP2 blocked the upregulation of NR2B
      phosphorylation induced by CFA injection. Taken together, our present results
      suggest that the arcuate Src activation-induced tyrosine phosphorylation of NR2B
      NMDA subunit may contribute to inflammatory pain.

PMID- 22993257
TI  - Cycle-by-cycle assembly of respiratory network activity is dynamic and
      stochastic.
AB  - Rhythmically active networks are typically composed of neurons that can be
      classified as silent, tonic spiking, or rhythmic bursting based on their
      intrinsic activity patterns. Within these networks, neurons are thought to
      discharge in distinct phase relationships with their overall network output, and
      it has been hypothesized that bursting pacemaker neurons may lead and potentially
      trigger cycle onsets. We used multielectrode recording from 72 experiments to
      test these ideas in rhythmically active slices containing the pre-Botzinger
      complex, a region critical for breathing. Following synaptic blockade,
      respiratory neurons exhibited a gradient of intrinsic spiking to rhythmic
      bursting activities and thus defied an easy classification into bursting
      pacemaker and nonbursting categories. Features of their firing activity within
      the functional network were analyzed for correlation with subsequent rhythmic
      bursting in synaptic isolation. Higher firing rates through all phases of fictive
      respiration statistically predicted bursting pacemaker behavior. However, a cycle
      by-cycle analysis indicated that respiratory neurons were stochastically
      activated with each burst. Intrinsically bursting pacemakers led some population
      bursts and followed others. This variability was not reproduced in traditional
      fully interconnected computational models, while sparsely connected network
      models reproduced these results both qualitatively and quantitatively. We
      hypothesize that pacemaker neurons do not act as clock-like drivers of the
      respiratory rhythm but rather play a flexible and dynamic role in the initiation
      and stabilization of each burst. Thus, at the behavioral level, each breath can
      be thought of as de novo assembly of a stochastic collaboration of network
      topology and intrinsic properties.

PMID- 22993258
TI  - Changes in taste receptor cell [Ca2+]i modulate chorda tympani responses to
      bitter, sweet, and umami taste stimuli.
AB  - The relationship between taste receptor cell (TRC) intracellular Ca(2+)
      ([Ca(2+)](i)) and rat chorda tympani (CT) nerve responses to bitter (quinine and
      denatonium), sweet (sucrose, glycine, and erythritol), and umami [monosodium
      glutamate (MSG) and MSG + inosine 5'-monophosphate (IMP)] taste stimuli was
      investigated before and after lingual application of ionomycin (Ca(2+) ionophore)
      + Ca(2+), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl
      ester (BAPTA-AM; Ca(2+) chelator), U73122 (phospholipase C blocker), thapsigargin
      (Ca(2+)-ATPase blocker), and diC8-PIP(2) (synthetic phosphatidylinositol 4,5
      bisphosphate). The phasic CT response to quinine was indifferent to changes in
      [Ca(2+)](i). However, a decrease in [Ca(2+)](i) inhibited the tonic part of the
      CT response to quinine. The CT responses to sweet and umami stimuli were
      indifferent to changes in TRC [Ca(2+)](i). However, a decrease in [Ca(2+)](i)
      attenuated the synergistic effects of ethanol on the CT response to sweet stimuli
      and of IMP on the glutamate CT response. U73122 and thapsigargin inhibited the
      phasic and tonic CT responses to bitter, sweet, and umami stimuli. Although diC8
      PIP(2) increased the CT response to bitter and sweet stimuli, it did not alter
      the CT response to glutamate but did inhibit the synergistic effect of IMP on the
      glutamate response. The results suggest that bitter, sweet, and umami taste
      qualities are transduced by [Ca(2+)](i)-dependent and [Ca(2+)](i)-independent
      mechanisms. Changes in TRC [Ca(2+)](i) in the BAPTA-sensitive cytosolic
      compartment regulate quality-specific taste receptors and ion channels that are
      involved in the neural adaptation and mixture interactions. Changes in TRC
      [Ca(2+)](i) in a separate subcompartment, sensitive to inositol trisphosphate and
      thapsigargin but inaccessible to BAPTA and ionomycin + Ca(2+), are associated
      with neurotransmitter release.

PMID- 22993259
TI  - Dopamine exerts activation-dependent modulation of spinal locomotor circuits in
      the neonatal mouse.
AB  - Monoamines can modulate the output of a variety of invertebrate and vertebrate
      networks, including the spinal cord networks that control walking. Here we
      examined the multiple changes in the output of locomotor networks induced by
      dopamine (DA). We found that DA can depress the activation of locomotor networks
      in the neonatal mouse spinal cord following ventral root stimulation. By
      examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we
      found that DA depresses a putative recurrent excitatory pathway that projects
      onto rhythm-generating circuitry of the spinal cord. This depression was D(2) but
      not D(1) receptor dependent and was not due exclusively to depression of
      excitatory drive to motoneurons. Furthermore, the depression in excitation was
      not dependent on network activity. We next compared the modulatory effects of DA
      on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked
      rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we
      found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting,
      and increased amplitude. Overall, these data demonstrate that DA can potentiate
      network activity while at the same time reducing the gain of recurrent excitatory
      feedback loops from motoneurons onto the network.

PMID- 22993260
TI  - Decision making by urgency gating: theory and experimental support.
AB  - It is often suggested that decisions are made when accumulated sensory
      information reaches a fixed accuracy criterion. This is supported by many studies
      showing a gradual build up of neural activity to a threshold. However, the
      proposal that this build up is caused by sensory accumulation is challenged by
      findings that decisions are based on information from a time window much shorter
      than the build-up process. Here, we propose that in natural conditions where the
      environment can suddenly change, the policy that maximizes reward rate is to
      estimate evidence by accumulating only novel information and then compare the
      result to a decreasing accuracy criterion. We suggest that the brain approximates
      this policy by multiplying an estimate of sensory evidence with a motor-related
      urgency signal and that the latter is primarily responsible for neural activity
      build up. We support this hypothesis using human behavioral data from a modified
      random-dot motion task in which motion coherence changes during each trial.

PMID- 22993261
TI  - Selection of events in time enhances activity throughout early visual cortex.
AB  - Temporal selection poses unique challenges to the perceptual system. Selection is
      needed to protect goal-relevant stimuli from interference from new sensory input.
      In addition, contextual information that occurs at the same time as goal-relevant
      stimuli may be critical for learning. Using fMRI, we characterized how visual
      cortical regions respond to the temporal selection of auditory and visual
      stimuli. Critically, we focused on brain regions that are not involved in
      processing the target itself. Participants pressed a button when they heard a
      prespecified target tone and did not respond to other tones. Although more
      attention was directed to auditory input when the target tone was selected,
      activity in primary visual cortex increased more after target tones than after
      distractor tones. In contrast to spatial attention, this effect was larger in V1
      than in V2 and V3. It was present in regions not typically involved in
      representing the target stimulus. Additional experiments demonstrated that these
      effects were not due to multimodal processing, rare targets, or motor responses
      to the targets. Thus temporal selection of behaviorally relevant stimuli
      enhances, rather than reduces, activity in perceptual regions involved in
      processing other information.

PMID- 22993262
TI  - Potential confounds in estimating trial-to-trial correlations between neuronal
      response and behavior using choice probabilities.
AB  - Correlations between trial-to-trial fluctuations in the responses of individual
      sensory neurons and perceptual reports, commonly quantified with choice
      probability (CP), have been widely used as an important tool for assessing the
      contributions of neurons to behavior. These correlations are usually weak and
      often require a large number of trials for a reliable estimate. Therefore,
      working with measures such as CP warrants care in data analysis as well as
      rigorous controls during data collection. Here we identify potential confounds
      that can arise in data analysis and lead to biased estimates of CP, and suggest
      methods to avoid the bias. In particular, we show that the common practice of
      combining neuronal responses across different stimulus conditions with z-score
      normalization can result in an underestimation of CP when the ratio of the
      numbers of trials for the two behavioral response categories differs across the
      stimulus conditions. We also discuss the effects of using variable time intervals
      for quantifying neuronal response on CP measurements. Finally, we demonstrate
      that serious artifacts can arise in reaction time tasks that use varying
      measurement intervals if the mean neuronal response and mean behavioral
      performance vary over time within trials. To emphasize the importance of
      addressing these concerns in neurophysiological data, we present a set of data
      collected from V1 cells in macaque monkeys while the animals performed a
      detection task.

PMID- 22993263
TI  - Gating reaction mechanism of neuronal NMDA receptors.
AB  - The activation mechanisms of recombinant N-methyl-d-aspartate receptors (NRs)
      have been established in sufficient detail to account for their single channel
      and macroscopic responses; however, the reaction mechanism of native NRs remains
      uncertain due to indetermination of the isoforms expressed and possible neuron
      specific factors. To delineate the activation mechanism of native NRs, we
      examined the kinetic properties of currents generated by individual channels
      located at the soma of cultured rat neurons. Cells were dissociated from the
      embryonic cerebral cortex or hippocampus, and on-cell single channel recordings
      were done between 4 and 50 days in vitro (DIV). We observed two types of kinetics
      that correlated with the age of the culture. When we segregated recordings by
      culture age, we found that receptors recorded from early (4-33 DIV) and late (25
      50 DIV) cultures had smaller unitary conductances but had kinetic profiles that
      matched closely those of recombinant 2B- or 2A-containing receptors,
      respectively. In addition, we examined the effects of cotransfection with
      postsynaptic density protein 95 or neuropilin tolloid-like protein 1 on
      recombinant receptors expressed in human embryonic kidney-293 cells. Our results
      add support to the view that neuronal cultures recapitulate the developmental
      patterns of receptor expression observed in the intact animal and demonstrate
      that the activation mechanism of somatic neuronal NRs is similar to that
      described for recombinant receptors of defined subunit composition.

PMID- 22993264
TI  - Synchronous and asynchronous electrically evoked motor activities during wind-up
      stimulation are differentially modulated following an acute spinal transection.
AB  - In this study, we used a novel technique to study reflex wind-up when the spinal
      cord is intact and following an acute spinal transection. Specifically, we
      evaluated reflex responses evoked by a series of 10 electrical pulses to the
      tibial or superficial peroneal nerves in 9 decerebrate adult cats, before and
      after an acute spinal transection. Electromyograms were recorded in four hindlimb
      muscles (lateral gastrocnemius, tibialis anterior, semitendinosus, and sartorius)
      to evaluate reflex amplitude, duration, and the temporal summation of reflex
      responses, so-called wind-up. We identified two distinct reflex responses evoked
      by electrical stimulation of the tibial or superficial peroneal nerves on the
      basis of their pattern of change following acute spinal transection, a short
      latency (~10 ms) compound action potential (CAP) that was followed by a burst of
      sustained activity (SA). Wind-up of CAP and SA amplitudes was clearly present
      when the spinal cord was intact but was drastically reduced after acute
      spinalization in some muscles. Moreover, CAP and SA reflex responses were
      differentially modified by the acute spinalization. When the effects of acute
      spinal transection were significant, CAP responses were increased after acute
      spinalization, whereas SA responses were reduced, suggesting that the two signals
      are regulated by different neuronal mechanisms. The present results provide the
      first assessment of reflex wind-up before and after an acute spinal transection
      in the same animals and indicate that different reflex components must be
      considered separately when evaluating changes in neuronal excitability following
      SCI.

PMID- 22993265
TI  - Dynamic modulation of intrinsic functional connectivity by transcranial direct
      current stimulation.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation
      technique capable of modulating cortical excitability and thereby influencing
      behavior and learning. Recent evidence suggests that bilateral tDCS over both
      primary sensorimotor cortices (SM1) yields more prominent effects on motor
      performance in both healthy subjects and chronic stroke patients than unilateral
      tDCS over SM1. To better characterize the underlying neural mechanisms of this
      effect, we aimed to explore changes in resting-state functional connectivity
      during both stimulation types. In a randomized single-blind crossover design, 12
      healthy subjects underwent functional magnetic resonance imaging at rest before,
      during, and after 20 min of unilateral, bilateral, and sham tDCS stimulation over
      SM1. Eigenvector centrality mapping (ECM) was used to investigate tDCS-induced
      changes in functional connectivity patterns across the whole brain. Uni- and
      bilateral tDCS over SM1 resulted in functional connectivity changes in widespread
      brain areas compared with sham stimulation both during and after stimulation.
      Whereas bilateral tDCS predominantly modulated changes in primary and secondary
      motor as well as prefrontal regions, unilateral tDCS affected prefrontal,
      parietal, and cerebellar areas. No direct effect was seen under the stimulating
      electrode in the unilateral condition. The time course of changes in functional
      connectivity in the respective brain areas was nonlinear and temporally
      dispersed. These findings provide evidence toward a network-based understanding
      regarding the underpinnings of specific tDCS interventions.

PMID- 22993266
TI  - Upper threshold of extracellular neural stimulation.
AB  - It is well known that spiking neurons can produce action potentials in response
      to extracellular stimulation above certain threshold. It is widely assumed that
      there is no upper limit to somatic stimulation, except for cellular or electrode
      damage. Here we demonstrate that there is an upper stimulation threshold, above
      which no action potential can be elicited, and it is below the threshold of
      cellular damage. Existence of this upper stimulation threshold was confirmed in
      retinal ganglion cells (RGCs) at pulse durations ranging from 5 to 500 MUs. The
      ratio of the upper to lower stimulation thresholds varied typically from 1.7 to
      7.6, depending on pulse duration. Computational modeling of extracellular RGC
      stimulation explained the upper limit by sodium current reversal on the
      depolarized side of the cell membrane. This was further confirmed by experiments
      in the medium with a low concentration of sodium. The limited width of the
      stimulation window may have important implications in design of the electro
      neural interfaces, including neural prosthetics.

PMID- 22993267
TI  - Hybrid voltage sensor imaging of electrical activity from neurons in hippocampal
      slices from transgenic mice.
AB  - Gene targeting with genetically encoded optical voltage sensors brings the
      methods of voltage imaging to genetically defined neurons and offers a method of
      studying circuit activity in these selected populations. The present study
      reports the targeting of genetically encoded hybrid voltage sensors (hVOS) to
      neurons in transgenic mice. The hVOS family of probes employs a membrane-targeted
      fluorescent protein, which generates voltage-dependent fluorescence changes in
      the presence of dipicrylamine (DPA) as the result of a voltage-dependent optical
      interaction between the two molecules. We generated transgenic mice with two
      different high-performance hVOS probes under control of a neuron-specific thy-1
      promoter. Hippocampal slices from these animals present distinct spatial patterns
      of expression, and electrical stimulation evoked fluorescence changes as high as
      3%. Glutamate receptor and Na(+) channel antagonists blocked these responses. One
      hVOS probe tested here harbors an axonal targeting motif (from GAP-43) and shows
      preferential expression in axons; this probe can thus report axonal voltage
      changes. Voltage imaging in transgenic mice expressing hVOS probes opens the door
      to the study of functional activity in genetically defined populations of neurons
      in intact neural circuits.

PMID- 22993268
TI  - Chronic destructive pulmonary tuberculosis: assessment of disease activity by
      computed tomography.
AB  - BACKGROUND: Determination of disease activity of chronic destructive pulmonary
      tuberculosis (TB) on imaging studies can be difficult because several imaging
      findings due to disease chronicity such as a residual cavity can be
      misinterpreted as an active disease. PURPOSE: To evaluate computed tomography
      (CT) findings to predict active disease in patients with chronic destructive
      pulmonary TB. MATERIAL AND METHODS: CT findings of 36 patients with chronic
      active destructive pulmonary TB and 78 patients with chronic inactive destructive
      pulmonary TB were reviewed and their patterns of lung lesions were compared.
      Statistical comparisons were performed using chi-square and Student's T tests for
      univariate analyses, and a stepwise logistic regression method was used for
      multivariate analysis. RESULTS: Based on univariate analyses, cavitary
      destruction (P = 0.015), non-branching centrilobular nodules (P < 0.001), tree-in
      bud pattern (P < 0.001), airspace nodules (P < 0.001), and cavities in other
      lobes (P = 0.001) were more frequently seen in chronic active destructive
      pulmonary TB. A stepwise logistic regression analysis demonstrated that tree-in
      bud pattern (odds ratio, 52.3; 95% confidence interval, 6.2-437.2; P < 0.001)
      were significant CT findings associated with active disease. CONCLUSION: Tree-in
      bud pattern were the most characteristic CT findings to predict active disease in
      patients with chronic destructive pulmonary TB.

PMID- 22993269
TI  - MDCT has the potential to predict percutaneous coronary intervention outcome in
      swine model: microscopic validation.
AB  - BACKGROUND: Volumes and sizes of dislodged coronary microemboli vary during PCI
      so their effects at the left ventricular (LV) and cellular levels cannot be
      quantified. Furthermore, biopsy for tissue characterization is not an option in
      PCI patients. PURPOSE: To characterize and validate microinfarct size, LAD
      territory where microinfarct were found using multidetector computed tomography
      (MDCT), histochemical staining and microscopy as a function of microemboli
      volumes and to scale the effects of microemboli volumes on LV function. MATERIAL
      AND METHODS: Under X-ray guidance, a 3F catheter was inserted into LAD coronary
      artery of 14 pigs for delivering 16 mm(3) or 32 mm(3) of 40-120 MUm microemboli.
      MDCT imaging/histochemical staining/microscopy were performed 3 days later and
      used to characterize regional and global structural and functional changes in LV
      by threshold/planimetric methods. RESULTS: MDCT and ex-vivo methods were able to
      quantify microinfarct size and LAD territory where microinfarct was found as a
      function of volumes. However, MDCT and histochemical staining significantly
      underestimated microinfarct size and territory where microinfarct was found
      compared with microscopy. MDCT demonstrated the functional changes and showed a
      moderate correlation between LV ejection fraction and microinfarct size (r =
      0.53). Microscopy provided higher spatial resolution for measuring islands of
      necrotic cells, which explains the difference in measuring structural changes.
      CONCLUSION: MDCT showed the difference in microinfarct size and LAD territory as
      a function of microemboli volumes and scaled the changes in LV function. This
      experimental study gives clinicians a reference for the effects of defined
      microemboli volumes on myocardial viability and LV function and the under
      estimation of microinfarct on MDCT.

PMID- 22993270
TI  - Cardiac output obtained from test bolus injections as a factor in contrast
      injection rate revision of following coronary CT angiography.
AB  - BACKGROUND: Optimal contrast enhancement is crucial for the detection of coronary
      artery stenoses and atherosclerotic changes in coronary CT angiography (CTA).
      PURPOSE: To demonstrate the feasibility of using the cardiac output (CO) obtained
      from the test bolus injection data-set (COtest) as a factor in contrast injection
      rate revision of the following coronary CTA. MATERIAL AND METHODS: The test bolus
      injection data-sets of 52 consecutive coronary CTAs were examined. COtest was
      calculated from the test bolus data-set. Aortic peak enhancement (APE) was
      measured on the following coronary CTA. We simulated the APE at a fixed contrast
      injection rate of 4 mL/s (simAPE) in each patient. RESULTS: The ranges of COtest
      and simAPE were 2.82-7.56 L/min and 194-527 Hounsfield Units, respectively. There
      was a significant negative correlation (R = -0.802, P < 0.001) between simAPE and
      COtest. CONCLUSION: COtest can be used for injection rate revision on coronary
      CTA.

PMID- 22993271
TI  - A method for quantifying intervertebral disc signal intensity on T2-weighted
      imaging.
AB  - BACKGROUND: Quantification of intervertebral disc degeneration based on intensity
      of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean
      intensity of the region of interest (ROI) within the nucleus pulposus. However,
      the location and size of ROI have varied in different reports, and none of the
      reported methods can be considered fully objective. PURPOSE: To develop a more
      objective method of establishing ROIs for quantitative evaluation of signal
      intensity in the nucleus pulposus using T2-weighted MRI. MATERIAL AND METHODS: A
      1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288
      intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age
      was 47.4 years (range, 17-69 years). All discs were classified into five grades
      according to Pfirrmann et al. Discs in grades I and II were defined as bright
      discs, and discs in grades IV and V were defined as dark discs. Eight candidate
      methods of ROI determination were devised. The method offering the highest degree
      of discrimination between bright and dark discs was investigated among these
      eight methods. RESULTS: The method with the greatest degree of discrimination was
      as follows. The quadrangle formed by anterior and posterior edges of the upper
      and lower end plates in contact with the intervertebral disc to be measured was
      defined as the intervertebral area. A shape similar to the intervertebral area
      but with one-quarter the area was drawn. The geometrical center of the shape was
      matched to the center of intensity, and this shape was then used as the ROI.
      Satisfactory validity and reproducibility were obtained using this method.
      CONCLUSION: The present method offers adequate discrimination and could be useful
      for longitudinal tracking of intervertebral disc degeneration with sufficient
      reproducibility.

PMID- 22993272
TI  - (11)C-Methionine positron emission tomography may monitor the activity of
      encephalitis.
AB  - Encephalitis is generally diagnosed by clinical symptoms, cerebrospinal fluid
      examination, and imaging studies including CT, magnetic resonance imaging (MRI),
      and perfusion single photon emission tomography (SPECT). However, the role of
      positron emission tomography (PET) in diagnosis of encephalitis remains unclear.
      A 49-year-old woman presenting with coma and elevated inflammatory reaction was
      diagnosed as having encephalitis according to slow activity on
      electroencephalogram, broad cortical lesion in MR fluid attenuated inversion
      recovery image, and increased blood flow demonstrated by SPECT. PET revealed
      increased accumulation of (11)C-methionine (MET) in the affected brain tissues.
      After the symptom had improved 2 months later, the accumulation of MET as well as
      the abnormal findings of MR imaging and SPECT was normalized. This case indicated
      that MET PET may monitor the activity of encephalitis.

PMID- 22993274
TI  - Comment: H1N1 and neurologic disease in children.

PMID- 22993273
TI  - Blood pressure changes in acute ischemic stroke and outcome with respect to
      stroke etiology.
AB  - OBJECTIVE: Previous research suggested that proper blood pressure (BP) management
      in acute stroke may need to take into account the underlying etiology. METHODS:
      All patients with acute ischemic stroke registered in the ASTRAL registry between
      2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin
      Scale score >2. A local polynomial surface algorithm was used to assess the
      effect of baseline and 24- to 48-hour systolic BP (SBP) and mean arterial
      pressure (MAP) on outcome in patients with lacunar, atherosclerotic, and
      cardioembolic stroke. RESULTS: A total of 791 patients were included in the
      analysis. For lacunar and atherosclerotic strokes, there was no difference in the
      predicted probability of unfavorable outcome between patients with an admission
      BP of <140 mm Hg, 140-160 mm Hg, or >160 mm Hg (15.3 vs 12.1% vs 20.8%,
      respectively, for lacunar, p = 015; 41.0% vs 41.5% vs 45.5%, respectively, for
      atherosclerotic, p = 075), or between patients with BP increase vs decrease at 24
      48 hours (18.7% vs 18.0%, respectively, for lacunar, p = 0.84; 43.4% vs 43.6%,
      respectively, for atherosclerotic, p = 0.88). For cardioembolic strokes, increase
      of BP at 24-48 hours was associated with higher probability of unfavorable
      outcome compared to BP reduction (53.4% vs 42.2%, respectively, p = 0.037). Also,
      the predicted probability of unfavorable outcome was significantly different
      between patients with an admission BP of <140 mm Hg, 140-160 mm Hg, and >160 mm
      Hg (34.8% vs 42.3% vs 52.4%, respectively, p < 0.01). CONCLUSIONS: This study
      provides evidence to support that BP management in acute stroke may have to be
      tailored with respect to the underlying etiopathogenetic mechanism.

PMID- 22993275
TI  - Do cortical lesions help us to distinguish MS from NMO?

PMID- 22993276
TI  - Albuminuria and risk of stroke in African Americans: a marker of uncontrolled
      hypertension?

PMID- 22993278
TI  - Cerebral infarction in older age: nature or (lack of) nurture?

PMID- 22993277
TI  - Cerebral gray and white matter changes and clinical course in metachromatic
      leukodystrophy.
AB  - OBJECTIVE: Metachromatic leukodystrophy (MLD) is a rare metabolic disorder
      leading to demyelination and rapid neurologic deterioration. As therapeutic
      options evolve, it seems essential to understand and quantify progression of the
      natural disease. The aim of this study was to assess cerebral volumetric changes
      in children with MLD in comparison to normal controls and in relation to disease
      course. METHOD: Eighteen patients with late-infantile MLD and 42 typically
      developing children in the same age range (20-59 months) were analyzed in a cross
      sectional study. Patients underwent detailed genetic, biochemical,
      electrophysiologic, and clinical characterization. Cerebral gray matter (GM) and
      white matter (WM) volumes were assessed by multispectral segmentation of T1- and
      T2-weighted MRI. In addition, the demyelinated WM (demyelination load) was
      automatically quantified in T2-weighted images of the patients, and analyzed in
      relation to the clinical course. RESULTS: WM volumes of patients did not differ
      from controls, although their growth curves were slightly different. GM volumes
      of patients, however, were on average 10.7% (confidence interval 6.0%-14.9%, p <
      0.001) below those of normally developing children. The demyelination load
      (corrected for total WM volume) increased with disease duration (p < 0.003) and
      motor deterioration (p < 0.001). CONCLUSION: GM volume in patients with MLD is
      reduced when compared with healthy controls, already at young age. This supports
      the notion that, beside demyelination, neuronal dysfunction caused by neuronal
      storage plays an additional role in the disease process. The demyelination load
      may be a useful noninvasive imaging marker for disease progression and may serve
      as reference for therapeutic intervention.

PMID- 22993279
TI  - Cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in
      atrial fibrillation.
AB  - OBJECTIVE: To compare the cost-effectiveness of apixaban vs warfarin for
      secondary stroke prevention in patients with atrial fibrillation (AF). METHODS:
      Using standard methods, we created a Markov decision model based on the estimated
      cost of apixaban and data from the Apixaban for Reduction in Stroke and Other
      Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and other trials
      of warfarin therapy for AF. We quantified the cost and quality-adjusted life
      expectancy resulting from apixaban 5 mg twice daily compared with those from
      warfarin therapy targeted to an international normalized ratio of 2-3. Our base
      case population was a cohort of 70-year-old patients with no contraindication to
      anticoagulation and a history of stroke or TIA from nonvalvular AF. RESULTS:
      Warfarin therapy resulted in a quality-adjusted life expectancy of 3.91 years at
      a cost of $378,500. In comparison, treatment with apixaban led to a quality
      adjusted life expectancy of 4.19 years at a cost of $381,700. Therefore, apixaban
      provided a gain of 0.28 quality-adjusted life-years (QALYs) at an additional cost
      of $3,200, resulting in an incremental cost-effectiveness ratio of $11,400 per
      QALY. Our findings were robust in univariate sensitivity analyses varying model
      inputs across plausible ranges. In Monte Carlo analysis, apixaban was cost
      effective in 62% of simulations using a threshold of $50,000 per QALY and 81% of
      simulations using a threshold of $100,000 per QALY. CONCLUSIONS: Apixaban appears
      to be cost-effective relative to warfarin for secondary stroke prevention in
      patients with AF, assuming that it is introduced at a price similar to that of
      dabigatran.

PMID- 22993281
TI  - Breaking down barriers to identify hemorrhagic transformation in ischemic stroke.

PMID- 22993280
TI  - Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric
      hospitals.
AB  - OBJECTIVE: We sought to determine the range and extent of neurologic
      complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1'09) in
      children hospitalized with influenza. METHODS: Active hospital-based surveillance
      in 6 Australian tertiary pediatric referral centers between June 1 and September
      30, 2009, for children aged <15 years with laboratory-confirmed pH1N1'09.
      RESULTS: A total of 506 children with pH1N1'09 were hospitalized, of whom 49
      (9.7%) had neurologic complications; median age 4.8 years (range 0.5-12.6 years)
      compared with 3.7 years (0.01-14.9 years) in those without complications.
      Approximately one-half (55.1%) of the children with neurologic complications had
      preexisting medical conditions, and 42.8% had preexisting neurologic conditions.
      On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose,
      whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common
      neurologic complication (7.5%). Others included encephalitis/encephalopathy
      (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and
      paralysis/Guillain-Barre syndrome (0.4%). A total of 30.6% needed intensive care
      unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died.
      The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU
      stay was 4.4 days (median 1.5 days). CONCLUSIONS: Neurologic complications are
      relatively common among children admitted with influenza, and can be life
      threatening. The lack of specific treatment for influenza-related neurologic
      complications underlines the importance of early diagnosis, use of antivirals,
      and universal influenza vaccination in children. Clinicians should consider
      influenza in children with neurologic symptoms even with a paucity of respiratory
      symptoms.

PMID- 22993282
TI  - No MRI evidence of cortical lesions in neuromyelitis optica.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating
      disease of the CNS in which a pathogenic role of anti-aquaporin-4 (AQP4)
      antibodies has been suggested. Although AQP4 is expressed in human cortex, recent
      histologic studies have failed to find any evidence of cortical demyelination in
      NMO. OBJECTIVE: To evaluate, in vivo, the occurrence of focal and diffuse
      cortical pathology in NMO. METHODS: We studied 30 patients with NMO, 30 patients
      with relapsing-remitting multiple sclerosis (RRMS), and 30 normal controls (NC).
      RRMS and NC were age- and gender-matched to NMO. The presence of cortical lesions
      (CLs) was evaluated on double inversion recovery sequence and cortical thickness
      (CTh) by the application of Freesurfer on 3 volumetric fast field echo T1
      weighted images. RESULTS: No CL was observed in NC or in NMO, while 83 CLs were
      identified in 20/30 (66.7%) patients with RRMS. Although NMO did not differ from
      NC in the global CTh, a mild thinning was observed in some cortical areas
      (postcentral [p = 0.018], precentral [p = 0.009], and calcarine [p = 0.015] gyri)
      and in the thalamus (p = 0.036). Global and regional cortical thickness was
      significantly decreased in RRMS compared to both NMO and NC. DISCUSSION: Our in
      vivo data further suggest that the immune-mediated pathologic process occurring
      in NMO spares most of the cortex. NMO differs from multiple sclerosis, where CLs
      and atrophy are frequently found, even in early disease phases. Thus, MRI
      analysis of the cortex may be a potential diagnostic tool, especially in
      ambiguous cases.

PMID- 22993283
TI  - Revisiting the issue of mitochondrial DNA content in optic mitochondriopathies.

PMID- 22993284
TI  - OPA1 mutations induce mtDNA proliferation in leukocytes of patients with dominant
      optic atrophy.

PMID- 22993285
TI  - Racial differences in albuminuria, kidney function, and risk of stroke.
AB  - BACKGROUND: The objective of this study was to examine the joint associations of
      estimated glomerular filtration rate (eGFR) and urinary albumin excretion with
      incident stroke in a large national cohort study. METHODS: Associations of
      urinary albumin to creatinine ratio (ACR) and eGFR with incident stroke were
      examined in 25,310 participants of the Reasons for Geographic and Racial
      Differences in Stroke (REGARDS) study, a prospective study of black and white US
      adults >=45 years of age. RESULTS: A total of 548 incident strokes were observed
      over a median of 4.7 years of follow-up. Higher ACR values were associated with
      lower stroke-free survival in both black and white participants. Among black
      participants, as compared to an ACR <10 mg/g, the hazard ratios of stroke
      associated with an ACR of 10-29.99, 30-300, and >300 mg/g were 1.41 (95%
      confidence interval [CI] 1.01-1.98), 2.10 (95% CI 1.48-2.99), and 2.70 (95% CI
      1.58-4.61), respectively, in analyses adjusted for traditional stroke risk
      factors and eGFR. In contrast, the hazard ratios among white subjects were only
      modestly elevated and not statistically significant after adjustment for
      established stroke risk factors. eGFR <60 mL/min/1.73 m(2) was not associated
      with incident stroke in black or white participants after adjustment for
      established stroke risk factors. CONCLUSIONS: Higher ACR was independently
      associated with higher risk of stroke in black but not white participants from a
      national cohort. Elucidating the reasons for these findings may uncover novel
      mechanisms for persistent racial disparities in stroke.

PMID- 22993286
TI  - Neurologic manifestations of E coli infection-induced hemolytic-uremic syndrome
      in adults.
AB  - OBJECTIVE: To describe the neurologic and neuroradiologic complications of Shiga
      toxin producing Escherichia coli infection (STEC)-associated hemolytic-uremic
      syndrome (HUS) in adults. METHODS: All 52 adult patients with STEC O104:H4
      infection cared for at Hannover Medical School during the outbreak in Germany
      through May-July 2011 are considered in this observational study. Forty-three of
      the 52 patients underwent a standard neurologic diagnostic procedure including
      clinical examination, Mini-Mental State Examination, and Glasgow Coma Scale
      Score. Thirty-six patients underwent EEG, and 26 had cerebral MRI, 9 of them
      repeatedly. Case records of 9 patients who had not been seen by a neurologist
      were analyzed retrospectively. RESULTS: Forty-eight of the 52 patients had HUS.
      All but 1 of these showed neurologic symptoms. Focal neurologic signs like double
      vision, difficulties in finding words, or hyperreflexia were present in 23,
      additional deficits in orientation, attention, memory, or constructive abilities
      in 9, and marked impairment of consciousness in 15. MRI showed brainstem,
      midbrain, thalamus, corpus callosum, and white matter lesions in half of the
      patients, predominantly in diffusion-weighted images. The extent of MRI lesions
      did not correlate with clinical symptoms. General slowing but no focal alteration
      was found in half of the patients examined by EEG. CONCLUSION: Our findings
      suggest a toxic-metabolic pathology behind the neurologic impairment instead of
      multiple infarction due to microthrombosis. Future studies should aim to clarify
      if early antibiotic therapy or bowel cleansing might help to decrease the rate of
      neurologic complications in STEC-HUS.

PMID- 22993287
TI  - Serum tight-junction proteins predict hemorrhagic transformation in ischemic
      stroke patients.
AB  - OBJECTIVE: To evaluate the significance of circulating tight-junction (TJ)
      proteins as predictors of hemorrhagic transformation (HT) in ischemic stroke
      patients. METHODS: We examined 458 consecutive ischemic stroke patients, 7.2% of
      whom had clinically evident HT. None of the patients was treated with
      thrombolytic drugs. Serum levels of standard markers of blood-brain barrier (BBB)
      breakdown (S100B, neuron-specific enolase), TJ proteins (occludin [OCLN], claudin
      5 [CLDN5], zonula occludens 1 [ZO1]), and molecules involved in BBB
      disintegration (matrix metalloproteinase 9 and vascular endothelial growth factor
      [VEGF]) were assessed upon admission to the emergency department. A clinical
      deterioration caused by HT (cdHT) was defined as an increase of >=4 points in the
      NIH Stroke Scale score in combination with a visible HT on a CT scan performed
      immediately after the onset of new neurologic symptoms. RESULTS: Patients with
      cdHT had higher concentrations of OCLN, S100B, and the CLDN5/ZO1 ratio, and a
      lower level of VEGF than those without cdHT. CLDN5 levels also correlated with
      cdHT occurrence when estimated within 3 hours of stroke onset. We also
      demonstrated correlations between the levels of circulating TJ molecules and the
      level of S100B, which is a previously established marker of BBB disruption.
      CONCLUSIONS: Analyzing serum levels of TJ proteins, like CLDN5, OCLN, and
      CLDN5/ZO1 ratio, as well as S100B and VEGF, is an effective way to screen for
      clinical deterioration caused by HT in ischemic stroke patients, both within and
      after the IV thrombolysis time window.

PMID- 22993288
TI  - Deconditioning in patients with orthostatic intolerance.
AB  - OBJECTIVE: To study the frequency and degree of deconditioning, clinical
      features, and relationship between deconditioning and autonomic parameters in
      patients with orthostatic intolerance. METHODS: We retrospectively studied all
      patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and
      June 2011, who underwent both standardized autonomic and exercise testing.
      RESULTS: A total of 184 patients (84 with postural orthostatic tachycardia
      syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion
      criteria. Of these, 89% were women, and median age was 27.5 years (interquartile
      range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8). Of the
      patients, 90% had deconditioning (reduced maximum oxygen uptake [VO(2max)%] <85%)
      during exercise. This finding was unrelated to age, gender, or duration of
      illness. The prevalence of deconditioning was similar between those with POTS
      (95%) and those with orthostatic intolerance (91%). VO(2max)% had a weak
      correlation with a few autonomic and laboratory parameters but adequate
      predictors of VO(2max)% could not be identified. CONCLUSION: Reduced VO(2max)%
      consistent with deconditioning is present in almost all patients with orthostatic
      intolerance and may play a central role in pathophysiology. This finding provides
      a strong rationale for retraining in the treatment of orthostatic intolerance.
      None of the autonomic indices are reliable predictors of deconditioning.

PMID- 22993289
TI  - Blink reflex recovery cycle in patients with essential tremor associated with
      resting tremor.
AB  - OBJECTIVE: An increased R2 recovery component of the blink reflex (R2-BRrc) has
      been commonly observed in Parkinson disease, cranio-cervical dystonia, and
      dystonic tremor, while the BRrc was reported normal in patients with essential
      tremor (ET). We studied BRrc in patients with ET associated with resting tremor
      (rET) in comparison with patients with ET. METHODS: This was a cross-sectional
      study investigating R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200,
      300, 400, 500, and 750 msec in 14 patients with rET, 14 patients with ET, and 16
      healthy controls. To compare individual patients, we calculated an R2 recovery
      index in each subject as the mean of R2 area ratio values at ISIs of 150, 200,
      300, 400, and 500 msec. All patients and controls underwent DAT-SPECT. RESULTS:
      Patients with rET differed from those with ET for the presence of resting tremor
      associated in several cases (36%) with a subtle arm dystonia. DAT-SPECT was
      normal in all patients and controls. All patients with rET (with and without
      dystonia) had an increased R2-BRrc while all patients with ET had a normal BRrc
      comparable to that of control subjects. The R2 recovery index was abnormal in all
      patients with rET but in none of the patients with ET. CONCLUSIONS: Patients with
      rET showed increased R2-BRrc, suggesting that this form of tremor may be a
      dystonic tremor rather than a subtype of ET. BRrc helps to correctly diagnose DAT
      negative patients with resting tremor also in the absence of overt dystonic
      posturing.

PMID- 22993290
TI  - Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic
      Creutzfeldt-Jakob disease: report of the guideline development subcommittee of
      the American Academy of Neurology.
AB  - OBJECTIVE: To assess the available evidence for the diagnostic accuracy of CSF
      testing for protein 14-3-3 in patients with suspected sporadic Creutzfeldt-Jakob
      disease (sCJD). METHODS: The authors performed a systematic review of the
      available literature from 1995 to January 1, 2011, to identify articles involving
      patients who were suspected of having sCJD and who had CSF analysis for protein
      14-3-3. Studies were rated according to the American Academy of Neurology
      classification of evidence scheme for diagnostic studies, and recommendations
      were linked to the strength of the evidence. A pooled estimate of sensitivity and
      specificity was obtained for all studies rated Class II or higher. The question
      asked is "Does CSF 14-3-3 protein accurately identify Creutzfeldt-Jakob disease
      (CJD) in patients with sCJD?" RESULTS: The analysis was conducted on the basis of
      samples of 1,849 patients with suspected sCJD from 9 Class II studies. Assays for
      CSF 14-3-3 protein are probably moderately accurate in diagnosing sCJD:
      sensitivity 92% (95% confidence interval [CI] 89.8-93.6), specificity 80% (95% CI
      77.4-83.0), likelihood ratio of 4.7, and negative likelihood ratio of 0.10.
      RECOMMENDATION: For patients who have rapidly progressive dementia and are
      strongly suspected of having sCJD and for whom diagnosis remains uncertain
      (pretest probability ~20%-90%), clinicians should order CSF 14-3-3 assays to
      reduce the uncertainty of the diagnosis (Level B).

PMID- 22993292
TI  - Patient-empowerment interactive technologies.
AB  - Video games capture the rapt attention of an individual player's mind and body,
      providing new opportunities for personalized health care. An example of
      therapeutic interactive technologies is an incentive-based video game that
      translates physical exercise into mental empowerment via motivational metaphoric
      visualization in order to help patients psychologically overcome cancer. Such
      nonpharmacological interventions may enhance patients' resilience toward various
      chronic disorders via neuronal mechanisms that activate positive emotions and the
      reward system.

PMID- 22993291
TI  - Emotional neglect in childhood and cerebral infarction in older age.
AB  - OBJECTIVE: The purpose of the study was to test the hypothesis that a higher
      level of childhood adversity is associated with increased risk of cerebral
      infarction in old age. METHODS: Older participants in a longitudinal clinical
      pathologic study rated adverse childhood experiences (e.g., emotional neglect,
      parental intimidation and violence) on a previously established 16-item scale.
      During a mean of 3.5 years of follow-up, there were 257 deaths, with 206 brain
      autopsies (80.2). Number of chronic cerebral infarcts (gross plus microscopic;
      expressed as 0, 1, or >1) was determined in a uniform neuropathologic
      examination, which had been completed in 192 individuals at the time of these
      analyses. RESULTS: Childhood adversity scores ranged from 0 to 31 (mean = 8.3, SD
      = 6.4). In an ordinal logistic regression model adjusted for age, sex, and
      education, higher adversity was associated with higher likelihood of chronic
      cerebral infarction. In analyses of childhood adversity subscales, only emotional
      neglect was associated with infarction (odds ratio [OR] = 1.097; 95% confidence
      interval [CI] 1.048-1.148). The likelihood of infarction was 2.8 times higher
      (95% CI 2.0-4.1) in those reporting a moderately high level of childhood
      emotional neglect (score = 6, 75th percentile) vs a moderately low level of
      neglect (score = 1, 25th percentile). Results were comparable in subsequent
      analyses that controlled for lifetime socioeconomic status, cardiovascular risk
      factors, and an anxiety-related trait. CONCLUSION: Emotional neglect in childhood
      may be a risk factor for cerebral infarction in old age.

PMID- 22993293
TI  - Childhood disorders of the synapse: challenges and opportunities.
AB  - Earlier this year, a diverse group convened at the Jan and Dan Duncan
      Neurological Research Institute and Baylor College of Medicine to discuss
      research on neurodevelopmental disorders involving the synapse. Participants
      discussed current challenges in the field and made recommendations for future
      research directions.

PMID- 22993294
TI  - Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults
      with fragile X syndrome: a randomized, controlled, phase 2 trial.
AB  - Research on animal models of fragile X syndrome suggests that STX209, a gamma
      aminobutyric acid type B (GABA(B)) agonist, might improve neurobehavioral
      function in affected patients. We evaluated whether STX209 improves behavioral
      symptoms of fragile X syndrome in a randomized, double-blind, placebo-controlled
      crossover study in 63 subjects (55 male), ages 6 to 39 years, with a full
      mutation in the FMR1 gene (>200 CGG triplet repeats). We found no difference from
      placebo on the primary endpoint, the Aberrant Behavior Checklist-Irritability
      (ABC-I) subscale. In the other analyses specified in the protocol, improvement
      was seen on the visual analog scale ratings of parent-nominated problem
      behaviors, with positive trends on multiple global measures. Post hoc analysis
      with the ABC-Social Avoidance scale, a newly validated scale for the assessment
      of fragile X syndrome, showed a significant beneficial treatment effect in the
      full study population. A post hoc subgroup of 27 subjects with more severe social
      impairment showed improvements on the Vineland II-Socialization raw score, on the
      ABC-Social Avoidance scale, and on all global measures. STX209 was well
      tolerated, with 8% incidences of sedation and of headache as the most frequent
      side effects. In this exploratory study, STX209 did not show a benefit on
      irritability in fragile X syndrome. Nonetheless, our results suggest that GABA(B)
      agonists have potential to improve social function and behavior in patients with
      fragile X syndrome.

PMID- 22993295
TI  - Reversal of disease-related pathologies in the fragile X mouse model by selective
      activation of GABAB receptors with arbaclofen.
AB  - Fragile X syndrome (FXS), the most common inherited cause of intellectual
      disability and autism, results from the transcriptional silencing of FMR1 and
      loss of the mRNA translational repressor protein fragile X mental retardation
      protein (FMRP). Patients with FXS exhibit changes in neuronal dendritic spine
      morphology, a pathology associated with altered synaptic function. Studies in the
      mouse model of fragile X have shown that loss of FMRP causes excessive synaptic
      protein synthesis, which results in synaptic dysfunction and altered spine
      morphology. We tested whether the pharmacologic activation of the gamma
      aminobutyric acid type B (GABA(B)) receptor could correct or reverse these
      phenotypes in Fmr1-knockout mice. Basal protein synthesis, which is elevated in
      the hippocampus of Fmr1-knockout mice, was corrected by the in vitro application
      of the selective GABA(B) receptor agonist STX209 (arbaclofen, R-baclofen). STX209
      also reduced to wild-type values the elevated AMPA receptor internalization in
      Fmr1-knockout cultured neurons, a known functional consequence of increased
      protein synthesis. Acute administration of STX209 in vivo, at doses that modify
      behavior, decreased mRNA translation in the cortex of Fmr1-knockout mice.
      Finally, the chronic administration of STX209 in juvenile mice corrected the
      increased spine density in Fmr1-knockout mice without affecting spine density in
      wild-type mice. Thus, activation of the GABA(B) receptor with STX209 corrected
      synaptic abnormalities considered central to fragile X pathophysiology, a finding
      that suggests that STX209 may be a potentially effective therapy to treat the
      core symptoms of FXS.

PMID- 22993296
TI  - A paper-based multiplexed transaminase test for low-cost, point-of-care liver
      function testing.
AB  - In developed nations, monitoring for drug-induced liver injury through serial
      measurements of serum transaminases [aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite
      the need, monitoring for drug-related hepatotoxicity in resource-limited settings
      is often limited by expense and logistics, even for patients at highest risk.
      This article describes the development and clinical testing of a paper-based,
      multiplexed microfluidic assay designed for rapid, semiquantitative measurement
      of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained
      by venipuncture and 10 fingerstick specimens from healthy volunteers, we have
      shown that our assay can, in 15 min, provide visual measurements of AST and ALT
      in whole blood or serum, which allow the user to place those values into one of
      three readout "bins" [<3* upper limit of normal (ULN), 3 to 5* ULN, and >5* ULN,
      corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These
      data suggest that the ultimate point-of-care fingerstick device will have high
      impact on patient care in low-resource settings.

PMID- 22993297
TI  - Group IIa sPLA2 inhibition attenuates NF-kappaB activity and promotes apoptosis
      of lung cancer cells.
AB  - BACKGROUND/AIM: Group IIa secretory phospholipase A2 (sPLA2 IIa) has been
      implicated in the regulation of metastasis of non-small cell lung cancer (NSCLC)
      and the present study investigates its contribution to lung cancer growth and
      progression. PLA2s initiate signaling in several pathways that mediate cell
      survival including phosphatidylinositol 3-kinase-AKT (PI3K-AKT), p38 mitogen
      activated protein kinase (p38 MAPK), extracellular-signal-regulated kinase (ERK)
      and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB).
      MATERIALS AND METHODS: Human NSCLC cell lines (A549 and NCI-H358) were treated
      with a specific sPLA2 IIa inhibitor. Cells were assayed for apoptosis, viability,
      proliferation and changes in cell morphology. Effects on AKT, p38 MAPK, ERK1/2
      and NF-kappaB signaling pathways were investigated. RESULTS: sPLA2 IIa inhibition
      reduced proliferation and increased apoptosis. NF-kappaB activity was attenuated,
      whereas AKT, ERK1/2, p38 MAPK were variably affected by sPLA2 IIa inhibition. NF
      kappaB inhibitor-associated apoptosis confirmed the dominant role of NF-kappaB.
      CONCLUSION: sPLA2 IIa attenuates growth and promotes apoptosis predominantly via
      its effects on NF-kappaB activity.

PMID- 22993298
TI  - From development to cancer: lessons from the kidney to uncover new therapeutic
      targets.
AB  - Several genes play essential roles in human development and alteration of their
      expression or regulation leads to various pathologies. This review examines the
      literature on the expression and the roles of neurogenic locus notch homolog
      protein (NOTCH), sonic Hedgehog (SHH) and wingless-type (WNT) pathways, as well
      as the nephrogenic transcription factors Wilms' tumor 1 (WT1), paired box 2
      (PAX2) and homeobox protein lim-1 (LIM1) in clear cell renal cell carcinoma.
      Besides being re-expressed in human tumors, the inhibition of these factors has
      strong antitumor activity both in vitro and in vivo. Interestingly, these
      pathways are also part of the molecular network involved in the development of
      organs including nephrogenesis. The identification of developmental pathways
      involved in clear cell renal cell carcinoma growth places an additional piece
      into the molecular puzzle of cancer mechanisms. Moreover, the evaluation of these
      molecules could pave the way to innovative and safe therapies for this refractory
      disease. Valuable prognostic markers might also be identified through these
      studies. Finally, the proof of concept in other types of cancer is reviewed.

PMID- 22993299
TI  - Prognostic impact of VEGFA germline polymorphisms in patients with HER2-positive
      primary breast cancer.
AB  - BACKGROUND: Vascular endothelial growth factor A (VEGFA) is essential in tumour
      angiogenesis, and polymorphisms in the VEGFA gene have been associated with
      breast cancer prognosis. The human epidermal growth factor receptor 2 (HER2) is
      overexpressed in breast tumours and is also associated with angiogenesis. We
      investigated the possible prognostic impact of VEGFA single nucleotide
      polymorphisms (SNPs) in patients with HER2-positive primary breast cancer.
      PATIENTS AND METHODS: DNA was isolated from venous blood samples from 116 HER2
      positive patients and genotyped for VEGFA -2578C>A, -1498T>C, -1154G>A, -634G>C, 
      7C>T and +936C>T SNPs using the TaqMan(r) SNP Genotyping Assay. RESULTS: The 
      2578C>A and -634G>C genotypes were associated with tumour size, p <= 0.014. In
      univariate analysis -2578CC, -634CC and -7CC genotypes were associated with
      inferior recurrence-free survival (p <= 0.028) but in cox multivariate analysis,
      only the -634CC genotype remained an independent prognostic factor (p=0.008).
      CONCLUSION: The VEGFA -634CC genotype was found to be associated with an inferior
      prognosis for patients with HER2-positive breast cancer.

PMID- 22993300
TI  - Whole-transcriptome analysis reveals established and novel associations with
      TMPRSS2:ERG fusion in prostate cancer.
AB  - BACKGROUND/AIM: Shortcomings of current methods of prostate cancer detection call
      for improved biomarkers. The transmembrane protease, serine 2:ets-related gene
      (TMPRSS2:ERG) gene fusion leads to the overexpression of ERG, an E-twenty six
      (ETS) family transcription factor, and is the most prevalent genetic lesion in
      prostate cancer, but its clinical utility remains unclear. MATERIALS AND METHODS:
      Two radical prostatectomy samples were analysed by next-generation whole
      transcriptome sequencing. The chosen samples differed in fusion gene status, as
      previously determined by reverse transcription polymerase chain reaction (RT
      PCR). RESULTS: Next-generation sequencing identified the involvement of novel and
      previously reported prostate cancer-related transcripts, the WNT signalling
      pathway, evasion of p53-mediated anti-proliferation and several ETS-regulated
      pathways in the prostate cancer cases examined. Overexpression of Rho GDP
      dissociation inhibitor (RhoGDIB), a gene associated with fusion-positive prostate
      cancer, was found to elicit spindle-shaped morphology, faster cell migration and
      increased cell proliferation, phenotypic changes suggestive of cancer
      progression. CONCLUSION: The present findings confirm the value of comprehensive
      sequencing for biomarker development and provide potential avenues of future
      study.

PMID- 22993301
TI  - Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF
      kappaB and MAPK pathways.
AB  - We previously reported that caffeine-assisted chemotherapy improved the treatment
      of malignant bone and soft tissue tumours such as osteosarcoma. Caffeine affects
      tumour cells through various pathways, including phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN), AKT, Bcl-2-associated X protein (BAX), caspase-3
      and p53, and has therefore been indicated as being useful for the treatment of
      malignant tumours. Here, the effects of caffeine on the proliferation of HOS
      osteosarcoma cells were assessed by WST-8 assay, and the effects on the nuclear
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), mammalian
      target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways
      were assessed by western blot analyses. Caffeine inhibited proliferation of HOS
      cells and suppressed NF-kappaB, AKT, mTOR/S6K and ERK activities. Our results
      support those from previous studies relating to the use of caffeine in the
      treatment of osteosarcoma.

PMID- 22993302
TI  - Comparative evaluation of small-molecule chemosensitizers in reversal of
      cisplatin resistance in ovarian cancer cells.
AB  - Cisplatin-resistance is one of the major challenges in the treatment of
      epithelial ovarian cancer. Small-molecule chemosensitizers provide a
      therapeutically feasible approach to overcome cisplatin resistance in ovarian
      cancer. However, proper selection of chemosensitizer is of prime importance owing
      to phenotypic differences in cisplatin-resistant ovarian cancers. The resistance
      reversal activity of chemosensitizers buthionine sulfoximine (BSO),
      triethylenetetramine (TETA), genistein, rapamycin and colchicine was investigated
      in various cisplatin-resistant ovarian cancer cells, 2008 C13, CP70 and OVCAR 8
      using MTT assays. Cellular accumulation of cisplatin in the presence of
      chemosensitizers was analyzed by inductively-coupled plasma-mass spectroscopy
      (ICP-MS). Chemosensitizers exhibited resistance reversal activity in 2008 C13 and
      CP70 cells in the following order; colchicine> genistein>TETA> rapamycin >= BSO
      (p<0.05), which is in correlation with cellular accumulation of cisplatin. In
      conclusion, our study demonstrates that resistance reversal activity of
      chemosensitizers varies with phenotypic behavior of cisplatin-resistant ovarian
      cancer cells. Data from our study can be utilized to choose a specific
      chemosensitizer for individualized combination therapy for cisplatin-resistant
      ovarian cancer.

PMID- 22993304
TI  - Administration of salubrinal enhances radiation-induced cell death of SW1353
      chondrosarcoma cells.
AB  - BACKGROUND: Chondrosarcoma is a common soft tissue malignancy. Although radiation
      induces DNA damage and integrated stress response (ISR), the sensitivity to
      ionizing radiation differs among tissues, and traditional radiotherapy for
      chondrosarcoma is not deemed effective. We examined whether administration of an
      ISR-inducing agent enhances radiosensitivity of chondrosarcoma. MATERIALS AND
      METHODS: SW1353 chondrosarcoma cells and C28/I2 chondrocytes were irradiated with
      1-10 Gy of X-rays and cultured with 1-20 MUM salubrinal, which is known to induce
      ISR through inhibiting dephosphorylation of eukaryotic translation initiation
      factor 2alpha (eIF2alpha). RESULTS: The numbers of cells were reduced after
      irradiation, and salubrinal further reduced them as well as their clonogenic
      survival. The levels of phosphorylated eIF2alpha were elevated by irradiation and
      administration of salubrinal. SW1353 cells treated with salubrinal after
      irradiation were more sensitive to radiation than those treated with salubrinal
      prior to irradiation. CONCLUSION: Salubrinal may serve as a potential
      chemotherapeutic agent for enhancing radiosensitivity, and its efficacy may
      depend upon the dose used and the timing of its administration.

PMID- 22993303
TI  - Complexation of albendazole with hydroxypropyl-beta-cyclodextrin significantly
      improves its pharmacokinetic profile, cell cytotoxicity and antitumor efficacy in
      nude mice.
AB  - BACKGROUND: Albendazole (ABZ) is a microtubule depolymerizing agent with a
      remarkable activity against a variety of tumor cells in vitro and in vivo.
      However, the lack of water solubility limits its application. Therefore, the aim
      of this study was to formulate ABZ with acetic acid/2-hydroxypropyl-beta
      cyclodextrin (HPbetaCD) with the view of improving its aqueous solubility and
      therefore, its antitumor efficacy. MATERIALS AND METHODS: ABZ was dissolved in
      acetic acid and 25% HPbetaCD (w/v). Mice received a single dose of ABZ/HPbetaCD
      or a conventional suspension in hydroxypropyl methyl cellulose (HPMC) over 24 h
      and the concentration of ABZ and its metabolites in plasma were measured by HPLC.
      The antitumor efficacy of the two formulations were then evaluated and compared
      in nude mice bearing HCT-116 colorectal cancer xenografts. RESULTS: Ionization
      with acetic acid together with complexation with hydroxylpropyl-beta-cyclodextrin
      (HPbetaCD) dramatically improved the solubility of ABZ. The area under the curve
      (AUC) of ABZ and its active metabolite, ABZ sulfoxide (ABZSO) were approximately
      2.3- and 7.3-folds higher in mice that received ABZ/HPbetaCD in comparison with
      animals that were treated with ABZ/HPMC. Additionally, the peak plasma
      concentration (C(max)) of ABZSO was nearly 18-times higher in mice that received
      ABZ/HPbetaCD. Furthermore, a significant delay in tumor growth that led to longer
      survival in mice was observed in the ABZ/HPbetaCD-treated group as compared to
      the ABZ/HPMC group. CONCLUSION: These findings demonstrate that the combination
      of acetic acid and HPbetaCD significantly improves the solubility,
      pharmacokinetic profile and antitumor efficacy of ABZ. This newly-developed
      formulation of ABZ may be suitable for parenteral administration.

PMID- 22993305
TI  - Renin-angiotensin system-regulating aminopeptidases in tumor growth of rat C6
      gliomas implanted at the subcutaneous region.
AB  - BACKGROUND: Angiotensin peptides play roles in brain tumor infiltration and
      associated angiogenesis. MATERIALS AND METHODS: We explored the roles of soluble
      and membrane-bound forms of renin-angiotensin system-regulating aminopeptidase N
      (APN)-, aminopeptidase B (APB)-, glutamate aminopeptidase- and aspartate
      aminopeptidase (AspAP)-specific activities on tumor growth in the rat C6 glioma
      model with implantation into the subcutaneous abdomen of Wistar rats, evaluating
      these activities as biological markers. The tumor volume was assessed for three
      weeks and a sample of tumor was obtained every seven days to obtain the soluble
      and membrane-bound fraction, in order to assay enzyme activities fluorometrically
      using their corresponding aminoacyl-beta-naphthylamide as substrates. RESULTS: We
      found a time-dependent decrease in soluble and membrane-bound APN and APB.
      Soluble AspAP increases with tumor growth in a time-dependent manner. CONCLUSION:
      Although gliomas are heterogeneous tissues, angiotensin peptides are involved in
      this model of tumor growth and their role could be analyzed through their
      corresponding regulatory proteolytic enzymes.

PMID- 22993306
TI  - Revisiting epithelial-to-mesenchymal transition through adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma (ACC) has a 5-year survival rate of 90%. The 15-year
      survival rate drops to 10% due to recurrence and invasion. ACC has three
      subtypes: cribriform, tubular, and solid. The cribriform subtype has the best
      prognosis and the solid subtype has the worst prognosis. By immunohistochemistry
      of tissue sections, we showed that the solid form expresses alphavbeta6 integrin
      and tenascin-C, which are known promoters of epithelial-to-mesenchymal transition
      (EMT). We also defined two ACC cell lines with the characteristics of the
      cribriform and solid subtype. The SACC83 cells grow in basaloid-like clusters and
      express high levels of E-cadherin. In contrast, the ACCh cells are more
      myoepithelial-like and express high levels of vimentin and of alphavbeta6
      integrin. The ACCh cells are highly invasive and this behavior is dependent upon
      the alphavbeta6 integrin function. Our results suggest that the transition from
      the cribriform to solid form may occur through EMT.

PMID- 22993307
TI  - A new chalcone derivative (E)-3-(4-methoxyphenyl)-2-methyl-1-(3,4,5
      trimethoxyphenyl)prop-2-en-1-one suppresses prostate cancer involving p53
      mediated cell cycle arrests and apoptosis.
AB  - Previous studies suggested chalcones as antineoplastic drug candidates. We
      synthesized a new chalcone derivative (E)-3-(4-methoxyphenyl)-2-methyl-1-(3,4,5
      trimethoxyphenyl)prop-2-en-1-one, (CHO27) with an up to 1000-fold increased
      cytotoxic potency relative to its parent compound in cell culture assays. CHO27
      at low nanomolar levels, inhibited prostate cancer (PCa) cell growth through cell
      cycle arrest and caspase-dependent apoptosis. Activation of p53 accounted for, at
      least in part, the growth inhibition by CHO27 in vitro. Furthermore, i.p.
      administration of CHO27 suppressed the growth of established PCa 22Rv1 xenograft
      tumors accompanied with p53 and p21(Cip1) induction. CHO27 may be a lead for
      development of new therapeutic agents for PCa.

PMID- 22993308
TI  - Site- and grade-specific diversity of LINE1 methylation pattern in
      gastroenteropancreatic neuroendocrine tumours.
AB  - BACKGROUND: Recent data indicate that gastroenteropancreatic neuroendocrine
      tumours (GEP-NETs) have a hypomethylated long interspersed element (LINE1)
      promoter. To answer the question, of whether LINE1 may be of value in assessing
      the malignant potential of GEP-NETs, we analysed LINE1 methylation in different
      organs. MATERIALS AND METHODS: A total of 58 GEP-NETs of gastric (n=14),
      pancreatic (n=15), small intestine (n=17), appendix (n=8), colorectal (n=4) and
      non-neoplastic tissues were analysed using DNA isolation, bisulphite-treatment
      and pyrosequencing. RESULTS: LINE1 hypomethylation was detected in 50% of
      gastric, 100% pancreatic, 82% small intestine, 87.5% appendix and 100% colorectal
      NETs. G1 (p<0.001) and G2 (p<0.05) colorectal, and G1 (p<0.001) and G2 (p<0.001)
      pancreatic NETs exhibited significant LINE1 hypomethylation compared with non
      neoplastic tissues. Higher rates of LINE1 hypomethylation in G2 pancreatic NETs
      than in G1 NETs (p<0.05) were observed. NETs exhibited a significantly lower
      frequency of hypomethylation in cases with lymph node metastases (p<0.05).
      CONCLUSION: LINE1 hypomethylation may serve as a marker of tumour grade and lymph
      node metastasis.

PMID- 22993309
TI  - Protein kinase C delta-mediated cytoskeleton remodeling is involved in aloe
      emodin-induced photokilling of human lung cancer cells.
AB  - Photodynamic therapy is becoming a widely accepted form of cancer treatment using
      a photosensitizing agent and light. Our previous study has demonstrated that
      photoactivated aloe-emodin induced anoikis and changes in cell morphology, which
      were in part mediated through its effect on cytoskeleton in lung carcinoma H460
      cells. However, the molecular mechanisms of these photoactivated aloe-emodin
      induced changes remain unknown. The present study demonstrated that the
      expression of protein kinase Cdelta (PKCdelta) was triggered by aloe-emodin and
      irradiation in H460 cells. Furthermore, the photoactivated aloe-emodin-induced
      cell death and translocation of PKCdelta from the cytosol to the nucleus was
      found to be significantly inhibited by rottlerin, a PKCdelta-selective inhibitor.
      Western blot analysis demonstrated that rottlerin also reversed the decrease in
      protein expression of cytoskeleton-related proteins, such as rat sarcoma (RAS),
      ras homolog gene family member A (RHO), p38, heat shock protein 27 (HSP27), focal
      adhesion kinase (FAK), alpha-actinin and tubulin, induced by photoactivated aloe
      emodin. Our findings suggest that the regulation of cytoskeleton-related proteins
      mediated by PKCdelta may be the mechanisms for the protective effects of
      rottlerin against the photoactivated aloe-emodin induced H460 cell death.

PMID- 22993310
TI  - PAR-1 polymorphisms and risk of Helicobacter pylori-related gastric cancer in a
      Chinese population.
AB  - BACKGROUND: PAR-1 has been involved in inflammation of the gastrointestinal
      tract, tumour cell growth and invasion of gastric carcinoma cells. Thus, we aimed
      at determining, for the first time, the association between PAR-1 - 506 ins/del
      and -IVSn-14 A/T and risk of Helicobacter pylori-related gastric cancer (GC) in
      an ethnic Chinese population. MATERIALS AND METHODS: A case-control study
      comprising of 225 ethnic Chinese individuals (77 non-cardia GC cases and 148
      controls with functional dyspepsia) was conducted. PAR-1 IVSn-14 A/T and 506
      ins/del were genotyped by means of real-time PCR and MALDI-TOF mass spectrometry,
      respectively. RESULTS: H. pylori infection, male gender and the PAR-1 IVSn-14 TT
      genotype increased GC risk (OR:3.15, 95% CI:1.54-6.45, OR:2.44, 95% CI:1.35-4.42
      and OR:2.58, 95% CI:1.09-6.13, respectively). PAR-1 -506 ins/del did not provide
      significant results. CONCLUSION: PAR-1 IVSn-14 T allele is a risk factor for H.
      pylori-related GC in ethnic Chinese subjects. PAR-1 -506 ins/del polymorphism is
      not involved in gastric carcinogenesis.

PMID- 22993311
TI  - An easy method to quantify plasma cells/plasma cell precursors in normal colonic
      mucosa, collagenous colitis and Crohn's colitis.
AB  - BACKGROUND: The number of round cells that should normally be present in the
      colonic mucosa remains disputed. Biopsies from patients with chronic diarrhoea,
      having a slightly increased number of round cells in the lamina propria mucosa
      (lpm) may be diagnosed as slight chronic colitis by some pathologists, while
      others may regard these biopsies as being normal. MATERIALS AND METHODS: The
      numbers of plasma cells/plasma cell precursors (PC-PCP) were assessed in colonic
      biopsies from 35 patients by the aid of MUM1 immunostaining. MUM1 (multiple
      myeloma oncogene 1) is a member of the interferon regulatory family of
      transcription factors (interferon regulatory factor 4 gene, IRF4). RESULTS: Many
      of the round cells considered, as lymphocytes in H&E staining were in fact MUM1
      positive PCP. In 6 patients having a priori, a slightly increased number of round
      cells, the mean number of MUM1-labelled cells was 40.8, in 5 patients with
      collagenous colitis, it was 81.4 and in 12 patients with Crohn's colitis, 87.6,
      whereas in 12 normal individuals it was 23.3 (MUM1-positive cells in collagenous
      Crohn's colitis vs. normal mucosa, p<0.05). CONCLUSION: MUM1 was of value in
      recording a significant increase of PC-PCP in collagenous colitis and Crohn's
      colitis. The subjective impression of increased cellularity in some colonic
      biopsies from patients with chronic diarrhoea was substantiated in mathematical
      terms, by demonstrating that the number of PC-PCP was increased.

PMID- 22993312
TI  - MicroRNAs in renal cell carcinoma: implications for pathogenesis, diagnosis,
      prognosis and therapy.
AB  - Renal cell carcinoma (RCC) is a potentially curable disease, especially if the
      tumor is limited to the kidneys and no systemic metastatic spread has occurred by
      the time of diagnosis. Despite the potential for successful surgical removal of
      the tumor-bearing organ in localized stages and the likelihood of treatment
      success, the complications and long-term morbidity and mortality of RCC are
      difficult to accurately predict. The currently used drugs were developed based on
      the understanding of the molecular details of pathogenesis at the time, which has
      improved over the past several decades. However, more efforts should be made to
      improve early diagnosis, the surveillance of patients who undergo resection and
      treatment for metastatic RCC. Recently, small non-coding RNAs (microRNAs) were
      found to play pivotal roles in the metastatic dissemination of tumor cells in
      different types of cancer. The aim of this review is to provide an overview of
      the role of microRNAs in the pathogenesis of RCC and to discuss their potential
      as diagnostic, prognostic and, ultimately, therapeutic biomolecules.

PMID- 22993313
TI  - Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential
      effects on normal melanocytes.
AB  - BACKGROUND/AIMS: To test the activity of novel hydroxyvitamin D(3) analogs
      (20(OH)D(3), 20,23(OH)(2)D and 1,20(OH)(2)D(3)) on normal and malignant
      melanocytes in comparison to 1,25(OH)(2)D(3). MATERIALS AND METHODS: Human
      epidermal melanocytes and human and hamster melanoma cells were used to measure
      effects on proliferation and colony formation in monolayer and soft agar. Cell
      morphology and melanogenesis were also analyzed. QPCR was used to measure gene
      expression. RESULTS: Novel secosteroids inhibited proliferation and colony
      formation by melanoma cells in a similar fashion to 1,25(OH)(2)D(3), having no
      effect on melanogenesis. These effects were accompanied by ligand-induced
      translocation of VDR to the nucleus. In normal melanocytes 1alpha
      hydroxyderivatives (1,25(OH)(2)D(3) and 1,20(OH)(2)D(3)) had stronger anti
      proliferative effects than 20(OH)D(3) and 20,23(OH)(2)D(3), and inhibited
      dendrite formation. The cells tested expressed genes encoding VDR and enzymes
      that activate or inactivate vitamin D(3). CONCLUSION: Novel secosteroids show
      potent anti-melanoma activity in vitro with 20(OH)D(3) and 20,23(OH)(2)D(3) being
      excellent candidates for pre-clinical testing.

PMID- 22993314
TI  - Gene therapy using adenovirus against malignant mesothelioma.
AB  - BACKGROUND: Adenovirus vectors have been utilized for cancer gene therapies. The
      present study examined the oncolytic effects of adenovirus type 5 (Ad5) and fiber
      substituted conditionally replicating adenovirus (CRAD) Ad5/F35 vectors on the
      human malignant mesothelioma cells MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452
      cells. MATERIALS AND METHOD: For the adenovirus, the first mRNA/protein to be
      made (~1 h after infection) is E1A. Ad5F35 and Ad5 CRAD vectors containing the E1
      gene controlled by the human midkine promoter (Ad5F35/MKp-E1 and Ad5/MKp-E1,
      respectively) were constructed. Western blotting and cell viability assays were
      carried out in cells transfected with Ad5/MKp-E1 and Ad5F35/MKp-E1. RESULTS:
      Coxsackie and adenovirus receptor (CAR), a cell surface target of Ad5, and CD46,
      a cell surface target of Ad35, were expressed in all the malignant mesothelioma
      cell lines examined here, as much as in HEK293 cells, with no significant
      differences in the expression levels among cells. Both Ad5/MKp-E1 and Ad5F35/MKp
      E1 induced oncolysis of malignant mesothelioma cells in a viral particle
      dependent manner, with similar efficacy. CONCLUSION: The results of the present
      study suggest that both Ad5/MKp-E1 and Ad5F35/MKp-E1 are useful for the gene
      therapy of human malignant mesothelioma.

PMID- 22993315
TI  - Pharmacokinetics of intravenous nitrosylcobalamin, an antitumor agent, in healthy
      Beagle dogs: a pilot study.
AB  - BACKGROUND/AIM: Nitrosylcobalamin (NO-Cbl) is a cobalamin-based anti-tumor agent.
      This study evaluated the pharmacokinetic parameters of NO-Cbl following
      intravenous administration in dogs. MATERIALS AND METHODS: Four dogs received 10
      mg/kg, 20 mg/kg and 40 mg/kg intravenous bolus doses of NO-Cbl, with a 14-day
      washout period between doses. Blood samples were collected at baseline and post
      dosing, and noncompartmental pharmacokinetic parameters were determined. RESULTS:
      Average peak serum concentrations of 2265, 5523 and 13,866 pg/mL were achieved
      following single-dose bolus intravenous administration of 10 mg/kg, 20 mg/kg and
      40 mg/kg of NO-Cbl respectively. The average area under the curve was 12,697 h *
      pg/mL, 24,497 h * pg/mL and 44,976 h * pg/mL respectively, with an average
      elimination half-life of 16.2 h, 13.5 h and 13.1 h respectively. CONCLUSION:
      These results can be used to determine the dose and dosing intervals for clinical
      trials evaluating NO-Cbl in humans and companion animals.

PMID- 22993316
TI  - Significance of ELF3 mRNA expression for detection of lymph node metastases of
      colorectal cancer.
AB  - BACKGROUND: Lymph node (LN) evaluation is an important factor for the prognosis
      of colorectal cancer (CRC). The purpose of our study was to investigate the
      effectiveness of E74-like factor 3 (ELF3) and carcinoembryonic antigen (CEA) as
      useful markers to detect LN metastases in CRC. MATERIALS AND METHODS: We examined
      the mRNA expression of ELF3 and CEA in LNs and tissues from 22 patients with CRC
      and in controls with ulcerative colitis (UC) by real-time quantitative reverse
      transcription polymerase chain reaction, as well as by hematoxylin-eosin
      staining. RESULTS: ELF3 and CEA expression showed statistically significant
      differences among four LN groups: LNs from patients with CRC categorized into
      three Dukes' stages and LNs from patients with UC (p<0.001 and p<0.001,
      respectively). We found a statistical correlation between the expression levels
      of both markers in patients with CRC compared with each Dukes' stage. CONCLUSION:
      ELF3, as a gene marker, may be sufficiently practical to detect LN metastases of
      CRC, rather than CEA.

PMID- 22993317
TI  - Extracellular ATP induces cytoplasmic and nuclear Ca2+ transients via P2Y2
      receptor in human biliary epithelial cancer cells (Mz-Cha-1).
AB  - Extracellular nucleotides such as adenosine triphosphate (ATP) play a role in
      biliary epithelial cell function. Since nucleotide receptors are potential
      targets for various diseases related to epithelial cell dysfunction and cancer,
      the purpose of this study was to investigate the expression and to functionally
      characterize the nucleotide receptor subtypes in biliary epithelial cancer cells
      (Mz-Cha-1). Extracellular ATP dose-dependently resulted in an intracellular
      Ca(2+) increase (mean effective concentration (EC(50)) 40 MUM). Uridine
      triphosphate (UTP) produced a similar Ca(2+) response and cross-desensitation was
      observed. The rank order of tested agonists was ATP=UTP>>
      adenosine>ADP=AMP>alpha,beta-methylene-ATP. This confirms the functional
      expression of purinoceptor P2Y2 and P2Y4 in biliary epithelial cancer cell
      membranes. mRNAs for P2Y1, P2Y2, P2Y4 and P2Y6 purinergic receptor subtypes were
      found, whereas western blot analysis suggested only the expression of P2Y2
      receptors. Confocal imaging and nuclear staining was used to compartmentalize ATP
      induced cytosolic and nuclear Ca(2+)-transients, indicating a role for secretory
      ATP in regulating nuclear function, by increasing nuclear Ca(2+) concentrations.
      These data define the expression profile of P2Y receptors on human biliary
      epithelial cancer cells and indicate P2Y2 receptors as being potential targets in
      new treatment strategies for biliary cancer.

PMID- 22993318
TI  - Evaluation of topical photodynamic therapy of mammary carcinoma with an
      experimental gel containing liposomal hydroxyl-aluminium phthalocyanine.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a clinically-accepted approach for the
      therapy of many types of cancer. This study focused on the treatment of mammarian
      carcinoma by topical administration of hydroxyl-aluminium phthalocyanine (AlOH
      PC), compared to a clinically-approved photosensitizer (Metvix, Galderma &
      PhotoCure ASA, Inc., Oslo, Norway). MATERIALS AND METHODS: MDA-MB 231 cells were
      subcutaneously injected into the right flank of athymic nude mice. Mice with
      grown tumours were used for in vivo efficacy studies. Different doses of
      liposomal AlOH-PC were applied to determine the most effective dose. In later
      studies, Metvix or our liposomal-AlOH-PC gel formula were used. Topical
      application of photosensitizers was followed by the PDT irradiation at 600-700 nm
      (635 nm peak). Tumour growth was measured three times weekly. RESULTS:
      Therapeutic studies revealed that AlOH-PC treatment led to complete tumour
      remission in 90% (9/10) of experimental animals, whereas usage of the
      commercially available Metvix only postponed the tumour growth. Moreover, usage
      of liposomal AlOH-PC shortened the time allowed between the application of the
      photosensitizer and light exposure: for Metvix, hours are usually needed, while
      the tested liposomal AlOH-PC showed remarkable outcomes after only 10 min.
      CONCLUSION: Liposomal AlOH-PC gel appears to be potentially suitable for PDT of
      mammarian carcinoma.

PMID- 22993319
TI  - Knockdown of receptor-interacting serine/threonine protein kinase-2 (RIPK2)
      affects EMT-associated gene expression in human hepatoma cells.
AB  - BACKGROUND: Receptor-interacting serine/threonine protein kinase-2 (RIPK2) has
      been reported to be an important regulator of tumor proliferation,
      differentiation and wound repair. We investigated the effects of RIPK2 knockdown
      in human hepatoma cells on epithelial-to-mesenchymal transition (EMT)-associated
      gene expression. MATERIALS AND METHODS: HepG2 cells stably expressing RIPK2-shRNA
      (HepG2-shRIPK2) were generated after puromycin selection. Total RNAs from HepG2
      shRIPK2 and from HepG2-shcontrol cells were isolated and PCR-based arrays were
      performed to compare the 84 EMT-associated gene expressions. RESULTS: We observed
      that knockdown of RIPK2 down-regulated mRNA expression of jagged 1 (JAG1);
      plasminogen activator inhibitor-1 (PAI1); regulator of G-protein signalling 2, 24
      kDa (RGS2); E-cadherin (CDH1); fibroblast growth factor binding protein 1
      (FGFBP1); snail homolog 2 (SNAI2); protein tyrosine phosphatase type IVA, member
      1 (PTP4A1); keratin 19 (KRT19); vimentin (VIM); and survival of motor neuron
      protein-interacting protein 1 (SIP1). CONCLUSION: We found that knockdown of
      RIPK2 down-regulated nuclear factor kappa B (NF-kappaB)-dependent PAI1 and VIM
      gene expressions. RIPK2 might play an important role in hepatic cell migration.
      These findings could shed new light on carcinogenesis and on liver regeneration.

PMID- 22993320
TI  - Prognostic value of acquired resistance-related molecules in Japanese patients
      with NSCLC treated with an EGFR-TKI.
AB  - BACKGROUND: Most patients with lung cancer experience relapse, although epidermal
      growth factor receptor (EGFR) of tyrosine kinase inhibitor (TKI) has an
      astounding effect on tumors with EGFR-activating mutations. It is therefore
      critical to determine the mechanisms of resistance against agents and the
      prognostic value of acquired resistance-related molecules to EGFR-TKI. MATERIALS
      AND METHODS: Tumor specimens were obtained from 19 matched specimens before and
      after treatment with gefitinib. A retrospective multi-institutional study
      analyzed the correlation between patients' survival and acquired resistance
      related molecules in non-small cell lung cancer (NSCLC) samples, that possessed
      sensitive EGFR mutations (7 cases: exon 19 deletion, and 12 cases: exon 21 point
      mutation). The status of the epidermal growth factor receptor (EGFR) and KRAS
      genes were investigated by polymerase chain reaction (PCR)-based analyses. Real
      time PCR assays were also used to evaluate MET gene amplification. The expression
      of hepatocyte growth factor (HGF) and changes in the epithelial-mesenchymal
      transition (EMT) status including the expression of E-cadherin and gamma-catenin
      as epithelial markers, and those of vimentin and fibronectin as mesenchymal
      markers, were evaluated by immunohistochemistry. RESULTS: Eight of the gefitinib
      refractory tumors exhibited a secondary threonine-to-methionine mutation at codon
      790 in EGFR (T790M). All of the tumors had wild type KRAS gene expression. No MET
      amplification was detected in any of the samples. A strong expression of HGF was
      detected in eight of the specimens at post-treatment. A change in the EMT status
      between pre-and post-treatment was found in five cases. The 5-year survival rate
      of patients with and without T790M was 86.7% and 13.3%, respectively (p=0.020).
      The 5-year overall survival (OS) rate for patients with overexpresion and for
      those with weak expression of HGF was 75.0% and 22.2%, respectively (p=0.259). In
      addition, the 5-year OS rate for patients with unchanged and changed EMT status
      was 83.3% and 40.0%, respectively (p=0.123). CONCLUSION: The current results
      showed that the presence of T790M is associated with favorable survival. On the
      other hand, the patients with weak HGF expression and EMT change tend to have a
      poor survival. The current patients' selection might be changed by discrimination
      of acquired resistance-related molecules in patients with NSCLC treated with an
      EGFR-TKI.

PMID- 22993321
TI  - The Effects of N-acetylcysteine on ifosfamide efficacy in a mouse xenograft
      model.
AB  - BACKGROUND/AIM: Nephrotoxicity is observed in 30% of children treated with
      ifosfamide. We have shown that n-acetylcysteine (NAC) successfully mitigates
      nephrotoxicity of ifosfamide in cell and rodent models. However, before this
      treatment is evaluated clinically, it must be established that NAC does not
      interfere with the efficacy of ifosfamide. MATERIALS AND METHODS: Mice implanted
      with Ewing's sarcoma tumours received the following treatments: saline,
      ifosfamide, ifosfamide + NAC concurrently, pre-treatment with NAC + ifosfamide,
      or NAC alone. RESULTS: Median volumes of EW-7 tumour xenografts in mice treated
      with ifosfamide (n=8), ifosfamide with concurrent NAC therapy (n=7), and NAC pre
      treatment (n=6) (p<0.05) were significantly reduced compared to median tumour
      volumes of control mice (n=6). None of the NAC treatments affected ifosfamide
      mediated reduction in tumour volumes. CONCLUSION: NAC does not interfere with the
      efficacy of ifosfamide in a EW-7 xenograft model. These results support the
      clinical evaluation of NAC as a strategy against ifosfamide-induced
      nephrotoxicity in children.

PMID- 22993322
TI  - The joint effect of smoking and hOGG1 genotype on oral cancer in Taiwan.
AB  - This study aimed at evaluating the association and interaction among human 8
      oxoguanine DNA N-glycosylase 1 (hOGG1) genotypic polymorphism, smoking status and
      oral cancer risk in Taiwan. For this purpose, the well-known polymorphic variants
      of hOGG1, codon 326, was analyzed for its association with oral cancer
      susceptibility, and its joint effect with individual smoking habits on oral
      cancer susceptibility. In total, 620 patients with oral cancer and 620 healthy
      controls were recruited from the China Medical Hospital and genotyped. The
      results showed that the hOGG1 codon 326 genotypes were differently distributed
      between the oral cancer and control groups (p=0.0266), with the C allele of hOGG1
      codon 326 being significantly (p=0.0046) more frequently found in cancer patients
      than in controls. We further analyzed the genetic-smoking joint effects on oral
      cancer risk and found an interaction between hOGG1 codon 326 genotypes and
      smoking status. The hOGG1 codon 326 CC genotype was associated with oral cancer
      risk only in the smoker group (p=0.0198), but not in the non-chewer group
      (p=0.8357). Our results provide evidence that the C allele of hOGG1 codon 326 may
      have a joint effect with smoking on the development of oral cancer.

PMID- 22993323
TI  - Significant anti-invasive activities of alpha-mangostin from the mangosteen
      pericarp on two human skin cancer cell lines.
AB  - AIM: This study aimed at investigating the anti-invasive activities of alpha
      mangostin on human melanoma SK-MEL-28 and squamous cell carcinoma A-431 cell
      lines. MATERIALS AND METHODS: Cytotoxicity was tested by the crystal violet
      assay; anti-invasive activity was detected by the wound healing, cell-matrix
      adhesion, and boyden chamber assays; and gene regulatory effects by qRT-PCR.
      Treatments were at non-toxic concentrations (0-1.25 MUg/ml for A-431 cells and 0
      2.5 MUg/ml for SK-MEL-28 cells). RESULTS: alpha-Mangostin inhibited motility,
      adhesion, migration and invasion. Invasive ability was reduced to 4% and 20%
      following alpha-mangostin treatment compared with untreated A-431 and SK-MEL-28
      cells, respectively. Inhibition of gene expression of MMP-2, MMP-9, NF-kappaB,
      and Akt1 was involved in the anti-invasive activities on A-431 cells. Inhibition
      of MMP-2, NF-kappaB and IkappaBalpha was involved for SK-MEL-28 cells.
      CONCLUSION: alpha-Mangostin suppressed the metastatic processes of SK-MEL-28 and
      A-431 cell lines by differentially regulating metastasis-related genes, showing
      potential as an anti-metastatic agent.

PMID- 22993324
TI  - Serum platelet-derived growth factor and fibroblast growth factor in patients
      with benign and malignant ovarian tumors.
AB  - BACKGROUND: New biological markers with predictive or prognostic value are highly
      warranted in the treatment of ovarian cancer. The platelet-derived growth factor
      (PDGF) system and fibroblast growth factor (FGF) system are important components
      in tumor growth and angiogenesis. MATERIALS AND METHODS: Pre-surgery peripheral
      blood samples were collected consecutively from 213 patients (42 with normal
      ovaries, 54 with benign, 21 with borderline, and 96 with malignant ovarian
      tumors) undergoing surgery for an untreated pelvic mass. Serum PDGF-AA, PDGF-BB,
      and FGF2 were quantified on a Luminex analyzer. RESULTS: Median PDGF-AA, PDGF-BB,
      and FGF2 levels were higher in patients with ovarian cancer than in those with
      borderline tumors, and normal ovaries, and PDGF-BB and FGF2 were also higher as
      compared to patients with benign tumors. PDGF-AA and PDGF-BB were associated with
      FIGO stage and residual tumor and PDGF-BB was associated with histological
      subtype. CONCLUSION: PDGF-AA, PDGF-BB, and FGF2 are up-regulated in ovarian
      cancer and levels of serum PDGF-AA and PDGF-BB seem to be associated with stage
      and residual tumor in ovarian cancer.

PMID- 22993325
TI  - Nuclear expression of Yes-associated protein 1 correlates with poor prognosis in
      intestinal type gastric cancer.
AB  - BACKGROUND: Yes-associated protein 1 (YAP1) is an effector of the Hippo pathway,
      which is critical for regulating organ size and cell proliferation in mammals. To
      investigate the prognostic value of YAP1 in gastric cancer (GC), we assessed its
      expression in tumors from patients. MATERIALS AND METHODS: We examined the
      nuclear expression of the YAP1 protein in 223 cases of GC, particularly of stage
      II and III disease, using immunohistochemistry. RESULTS: Positive nuclear
      expression of YAP1 was detected in 27.4% (61/223) of total GCs, 29.1% (34/117) of
      the intestinal-type GCs (IGC) and 25.5% (27/106) of the diffuse-type GCs (DGC).
      In the IGC group, we found that the overall survival rate among patients with
      YAP1 nuclear expression-positive tumors was lower than that in the expression
      negative group (p=0.021). Cox multivariate analysis revealed that the nuclear
      expression of YAP1 was an independent prognosticator of IGC (p=0.018).
      CONCLUSION: The nuclear overexpression of YAP1 is an independent biomarker for
      poor survival, especially for patients with intestinal-type gastric cancer.

PMID- 22993326
TI  - Correlation of expression of phosphorylated and non-phosphorylated Yes-associated
      protein with clinicopathological parameters in esophageal squamous cell carcinoma
      in a Korean population.
AB  - Yes-associated protein (YAP) is a nuclear downstream effector of the Hippo
      pathway, a regulator of cell growth. The phosphorylated form of YAP (pYAP),
      located in the cytoplasm, prevents cellular proliferation by spatially
      segregating YAP from the nucleus. This study aimed at investigating the
      relationships of pYAP and YAP with clinicopathological variables in esophageal
      squamous cell carcinoma (ESCC). Samples of ESCC from 142 patients were studied
      using immunohistochemistry for YAP, pYAP and Ki-67. In all cases of ESCC, higher
      nuclear expression of YAP was correlated with Ki-67 expression, tumor diameter,
      histological grade (1-2 versus 3), and pathological TNM stage (I versus II-IV) in
      univariate analyses (p=0.036, p=0.025, p=0.021, and p=0.033, respectively).
      Higher nuclear expression of YAP was associated with worse overall and disease
      free survival (p=0.006 and p=0.008, respectively). Multivariate analysis showed
      higher nuclear expression of YAP to be an independent prognostic marker for
      overall survival (p=0.034). We observed a trend towards inverse correlation of
      cytoplasmic pYAP expression and histological grade (1-2 versus 3) (p=0.087). Our
      results suggest that YAP shifts from the nucleus to the cytoplasm as a
      consequence of phosphorylation, which occurs in the presence of high tumor cell
      density in the case of ESCC, and may be a potential indication of histological
      differentiation. Nuclear expression of YAP is correlated with tumor cell
      proliferation and is an independent predictor of worse prognosis of ESCC.

PMID- 22993327
TI  - NAC1, a BTB/POZ protein overexpressed in uterine sarcomas.
AB  - BACKGROUND: The purpose of this study was to investigate the role of Nucleus
      accumbens-associated 1 (NAC1) in the development of uterine sarcomas. MATERIALS
      AND METHODS: NAC1 expression and localization in the normal myometrium, benign
      leiomyoma, and uterine sarcoma were assessed with immunohistochemistry. NAC1
      specific siRNA was used to inactivate NAC1 for in vitro biological assays.
      RESULTS: Almost all cases of uterine sarcoma were found to overexpress NAC1.
      Expression of NAC1 was significantly higher in uterine sarcomas than in benign
      leiomyomas (p<0.0001). NAC1 gene knockdown inhibited cell growth and induced
      apoptosis in SKN, a leiomyosarcoma cell line, and in OMC-9, an endometrial
      stromal sarcoma cell line, both of which overexpress NAC1. CONCLUSION: Uterine
      sarcomas with NAC1 overexpression are clinically the most aggressive,
      chemoresistant, and radioresistant tumors. Therefore, detection of NAC1
      overexpression in uterine sarcomas may identify patients who will benefit from
      NAC1-targeted therapy.

PMID- 22993328
TI  - Chemoresistance is associated with cancer stem cell-like properties and
      epithelial-to-mesenchymal transition in pancreatic cancer cells.
AB  - BACKGROUND: The aim of this study was to evaluate whether apoptosis-resistant
      cancer cells have cancer stem cell (CSC)-like properties. MATERIALS AND METHODS:
      Panc-1 pancreatic cancer cells were incubated in the presence of 5-fluorouracil
      (5-FU) for 24 h, and further incubated without 5-FU for 28 days. To assess the
      capacity of self-renewal, surviving cells were planted for sphere-forming assay.
      Epithelial-to-mesenchymal transition (EMT) was induced with TGF-beta, then mRNA
      expression was evaluated by real-time PCR for E-cadherin, SNAIL, and vimentin.
      The E-Cadherin protein levels were also examined by immunoblot analysis. The
      Local invasion ability was analyzed by Matrigel invasion assay. RESULTS: The
      frequency of cells that were capable of initiating spheres was higher in 5-FU-pre
      treated cells, which also overexpressed stem cell marker genes, OCT4 and NANOG.
      Matrigel invasion activity of apoptosis-resistant Panc-1 cells was greater than
      that of control Panc-1 cells. CONCLUSION: Apoptosis-resistant cancer cells have
      CSC-like properties, i.e., able to initiate sphere formation, express stem cell
      genes, and respond to EMT stimulation.

PMID- 22993329
TI  - The role of XRCC6 T-991C functional polymorphism in renal cell carcinoma.
AB  - BACKGROUND: The DNA non-homologous end-joining repair gene XRCC6 (Ku70) plays a
      key role in both the DNA double-strand break (DSB) repair and cell cycle arrest.
      Defects in DSB repair capacity can lead to genomic instability. We hypothesized
      that a variant in the XRCC6 gene was associated with susceptibility to renal cell
      carcinoma (RCC). MATERIALS AND METHODS: In a hospital-based case-control study of
      92 patients with RCC and 580 cancer-free controls, the frequency matched by age
      and sex, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C
      (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms
      with RCC risk were investigated in a Taiwanese population. At the same time, 30
      adjacent renal tissue samples were tested to estimate the XRCC6 mRNA expression
      by real-time quantitative reverse transcription. RESULTS: Compared with the TT
      genotype, the TC genotype had a significantly increased risk of RCC [adjusted
      odds ratio=2.24, 95% confidence interval=1.25-4.08, p=0.0175]. The in vivo mRNA
      expression in renal tissues revealed a statistically significant lower XRCC6 mRNA
      expression in samples with TC/CC genotypes compared to those with the TT genotype
      (p=0.0039). CONCLUSION: These evidence suggests that the XRCC6 T-991C genotype
      together with its mRNA expression are involved in the etiology of RCC and may be
      a marker for susceptibility to RCC in the population of Taiwan.

PMID- 22993330
TI  - Cancer immunotherapy by intratumoral injection of alpha-gal glycolipids.
AB  - AIM/ BACKGROUND: To determine the feasibility and safety of intratumoral alpha
      gal glycolipids injection for conversion of human tumors into autologous Tumor
      Associated Antigens (TAA) vaccine. alpha-Gal glycolipids bind anti-Gal--the most
      abundant antibody in humans. Pre-clinical studies indicated that injected alpha
      gal glycolipids insert into tumor cell membranes, bind anti-Gal and target tumor
      cells to Antigen Presenting Cells, thereby converting tumors into autologous TAA
      vaccines. We hypothesized that alpha-gal glycolipids might have similar utility
      in humans. PATIENTS AND METHODS: Eleven patients with advanced solid tumors
      received one intratumoral injection of 0.1 mg, 1 mg, or 10 mg alpha-gal
      glycolipids. The primary endpoint was dose-limiting toxicity (DLT) within 4
      weeks. Secondary endpoints included long-term toxicity, autoimmunity,
      radiological tumor response and survival. RESULTS: There were no DLT and no
      clinical or laboratory evidence of autoimmunity, or any other toxicity. Few
      patients had an unexpectedly long survival. CONCLUSION: Intratumoral injection of
      alpha-gal glycolipids is feasible and safe for inducing a protective anti-tumor
      immune response.

PMID- 22993331
TI  - The expression of CYP2W1: a prognostic marker in colon cancer.
AB  - AIM: The enzyme Cytochrome P450 2W1 (CYP2W1) is found in fetal colon tissue and
      is also detected in colorectal cancer but not in non-transformed tissue. In a
      pilot study, we reported that the immunohistochemically-detected expression of
      CYP2W1 might be of prognostic value since high expression of CYP2W1 was
      indicative of a worse prognosis. The aim of this study was to validate the pilot
      study's results using a larger, independent group of patients with colon cancer.
      MATERIALS AND METHODS: Immunohistochemical detection of CYP2W1 in 235 malignant
      colon tumors of stage II and III, was carried out using a polyclonal antibody.
      Grading of staining was carried out by two independent readers. The highest grade
      that involved more than 5% of the tumor area on each slide was used for the
      classification of CYP2W1 expression. RESULTS: CYP2W1 was expressed at high levels
      in 30% of the tumors. In the entire colon cancer group it was an independent
      prognostic factor in multivariate analysis (p=0.04), where high expression (grade
      3) correlated with worse outcome. CYP2W1 expression was an independent prognostic
      factor in the subgroup of patients with colon cancer stage III (p=0.003), but not
      for those with stage II. In 107 cases, two slices from different areas of the
      same tumor were available, and no significant difference in CYP2W1 expression
      between the slices was observed (r=0.53, p<0.001). CONCLUSION: The results of the
      current study were in agreement with those of the previous pilot study and show
      that higher expression of CYP2W1 seems to be of prognostic value in colon cancer.
      Furthermore, we found equal expression in slices from two different areas of the
      same tumor. Since the CYP2W1 enzyme has been shown to catalytically activate
      compounds to cytotoxic products, the enzyme might be used as a novel drug target
      for the treatment of colon cancer.

PMID- 22993332
TI  - Effectiveness of a 12-month exercise program on physical performance and quality
      of life of breast cancer survivors.
AB  - AIM: The study aimed at determining whether physical exercise training improves
      the quality of life (QoL) and physical fitness of breast cancer survivors.
      PATIENTS AND METHODS: A total of 573 breast cancer survivors were randomized into
      an exercise or a control group, 12-months after adjuvant treatments. EORTC QLQ
      C30 and BR-23 questionnaires were used for evaluation of QoL, FACIT-F for fatigue
      and the Finnish modified version of Beck's 13-item depression scale (RBDI) for
      depression. Physical fitness was assessed by a 2-km walking test, and a figure-8
      running test and physical activity (PA) by metabolic equivalent (MET) hours per
      week (MET-h/wk). RESULTS: Figure-8 running time improved significantly among the
      patients of the intervention group compared with the controls (p<0.001). No
      significant between-group differences were observed in 2-km walking time, in PA,
      EORTC-QLQ-C30, BR-23, FACIT-F or BDI. However, there was a linear relationship
      between increased PA and improved QoL (p=0.006), irrespective of the
      intervention. CONCLUSION: Increase in physical activity was associated with
      improved QoL, but no effect of the exercise intervention was observed.

PMID- 22993333
TI  - Chemotherapy dose-intensity and survival for childhood medulloblastoma.
AB  - AIM: To determine the relationship between prescribed dose-intensity of
      chemotherapy and survival in childhood medulloblastoma. MATERIALS AND METHODS: A
      total of 55 trials from 1970-2009 were identified, 30 were eligible for analysis,
      with individual treatment regimes with 5-year (or more) outcome figures.
      Relationships of outcome to dose-intensity were analysed using weighted
      regression. RESULTS: Overall, 2,434 patients were identified, 1,010 were
      classified as 'standard'- and 671 as 'high'-risk patients, with 5-year overall
      survivals (OS) of 67.2% (95% Confidence Interval=60.5%-73.6%) and 47.6% (95%
      Confidence Interval=39.5%-55.7%), respectively. A protective effect for
      chemotherapy versus craniospinal radiotherapy alone (5-year OS of 58.2% versus
      51.6%) was found. Individually, vincristine, cisplatin, lomustine (CCNU) and
      cyclophosphamide appear to confer the most beneficial effect, particularly for
      high-risk patients. Positive relationships between OS and dose-intensity were
      found, except for lomustine, with cyclophosphamide offering the greatest
      protection. CONCLUSION: Consideration of chemotherapy dose-intensity may further
      optimise treatment, particularly in the context of risk stratification.

PMID- 22993334
TI  - Gene expression profiling of adult t(4;11)(q21;q23)-associated acute
      lymphoblastic leukemia reveals a different signature from pediatric cases.
AB  - Chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene,
      located at chromosomal band 11q23, result in the generation of in-frame fusion
      transcripts with various partner genes from more than 60 distinct gene loci.
      Among them, the MLL/AFF1 (AF4/FMR2 family, member 1) fusion, associated with
      rearrangements between bands 4q21 and 11q23 is a recurrent event in pre-B acute
      lymphoblastic leukemia (ALL). Gene expression profiling (GEP) was performed for
      four adult patients with ALL. Their signatures were compared to those of ALL
      patients with a fusion gene involving c-abl oncogene 1, non-receptor tyrosine
      kinase (ABL1). The comparison of MLL-AFF1 cases with the ABL1 group identified
      477 genes being differentially expressed at the statistically significant level
      of p<0.05, with 296 and 181 genes up- and down-regulated, respectively, in the
      MLL-AFF1 cases. Three GEP studies on t(4;11)(q21;q23) focusing on the age group
      of the patients have been reported in the literature. Different expression
      profiles based on the levels of the homeobox A (HOXA) signature were identified.
      Although comparison between studies is difficult because of differences in the
      microarrays and the control samples used, our results and those from the
      literature suggest that cells carrying t(4;11)(q21;q23) use different pathways to
      lead to leukemogenesis. Therefore, t(4;11)-associated ALL could represent
      different biological entities.

PMID- 22993335
TI  - Update on PEG-interferon alpha-2b as adjuvant therapy in melanoma.
AB  - Based on the results of European Organization for Research and Treatment of
      Cancer (EORTC) 18991 trial, the US Food and Drug Administration (FDA) approved
      PEG-interferon alpha-2b (PEG-IFN) (Sylatron) as adjuvant therapy for high-risk
      melanoma. The EORTC 18991 trial was an open-label study of resectable stage III
      melanoma with 1,256 patients who were randomized to observation-alone or to
      treatment with PEG-IFN for up to 5 years. The median recurrence-free survival of
      the treatment groups was significantly longer, while overall survival, a
      secondary endpoint, was not significantly different between the two groups. This
      review, after a short summary of interferon alpha-2b trials, critically analyzes
      the EORTC18991 trial, as well as the subgroup results and future perspectives for
      this stage of disease.

PMID- 22993336
TI  - Complete pathologic response to neoadjuvant radiotherapy is predictive of
      oncological outcome in patients with soft tissue sarcoma.
AB  - We sought to determine if complete pathological necrosis (pathCR) predicts
      favorable oncological outcome in soft tissue sarcoma (STS) patients receiving pre
      operative radiation monotherapy (RT). PATIENTS AND METHODS: We evaluated 30
      patients with primary STS treated with neoadjuvant RT followed by definitive
      resection, from 2000 to 2010 at our institution. We defined >= 95% tumor necrosis
      as pathCR. RESULTS: There were 22 STS of the extremities (73%), 7 of the
      retroperitoneum (23%), and 1 (4%) of the trunk. The median pathological
      percentage of tumor necrosis was 35% (range 5-100%) with three tumors (10%)
      demonstrating pathCR. With a median follow-up of 40 months, the 5-year local
      recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and
      overall survival (OS) for the entire cohort were 100%, 61% +/- 11%, and 69% +/-
      11%, respectively. Among patients with pathCR, 3-year DRFS was 100% compared to
      63+/-11% in patients without pathCR (p=0.28). CONCLUSION: Following neoadjuvant
      RT for STS, pathCR is associated with a clinically but not statistically
      significant 37% improvement in 3-year DRFS.

PMID- 22993337
TI  - Association of matrix metalloproteinase-1 polymorphisms with risk of COPD and
      lung cancer and survival in lung cancer.
AB  - BACKGROUND: The primary risk factor for chronic obstructive pulmonary disease
      (COPD) and non-small cell lung cancer (NSCLC) is cigarette smoking but shared
      susceptibility factors, such as variations in the matrix metalloproteinase-1
      (MMP1) gene, may also underlie both diseases. MATERIALS AND METHODS: Cases with
      prevalent COPD (n=167), incident NSCLC (n=242), or prevalent COPD plus incident
      NSCLC (n=128) were compared to disease-free controls (n=338) to assess six MMP1
      polymorphisms. The association between these polymorphisms and survival in NSCLC
      was also evaluated. RESULTS: Rs11292517 among African-Americans [odds ratio
      (OR)=5.48, 95% confidence interval (CI)=1.17-25.72] and rs2071230 among
      Caucasians (OR=2.51, 95% CI=1.09-5.77) appeared to be associated with NSCLC risk
      in the presence of COPD. Rs470558 appeared to be associated with survival in
      NSCLC among African-Americans (hazard ratio=3.94; 95%CI=1.14-13.63). No
      associations remained after adjusting for multiple comparisons. CONCLUSION:
      Polymorphisms in MMP1 were not consistently associated with prevalent COPD or
      incident NSCLC nor with survival in NSCLC.

PMID- 22993338
TI  - SERPINA1 and ELA2 polymorphisms are not associated with COPD or lung cancer.
AB  - BACKGROUND: Through their roles in tissue remodeling, variants in the genes that
      encode alpha1-antitrypsin (AAT) and neutrophil elastase (NE) were hypothesized to
      be associated with the risk of both chronic obstructive pulmonary disease (COPD)
      and non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Cases with
      prevalent COPD (n=145), incident NSCLC (n=203) or prevalent COPD plus NSCLC
      (n=118) were compared to disease-free controls (n=317), to assess two functional
      polymorphisms in serpin peptidase inhibitor, clade A, member 1 (SERPINA1), which
      encodes AAT, and eleven tagging polymorphisms in and around elastase 2 (ELA2),
      which encodes NE. All analyses were stratified by race. RESULTS: Among African
      Americans, the less efficient SERPINA1 variant appeared to be associated with
      increased risk of prevalent COPD but only in the presence of NSCLC (odds
      ratio=7.39; 95% confidence interval=1.03-53.21) and not after correcting for
      multiple comparisons. CONCLUSION: Variations in SERPINA1 and ELA2 were not
      consistently or strongly associated with the risk of either COPD or NSCLC in
      either race.

PMID- 22993339
TI  - Detection and quantification of human papillomavirus in benign and malignant
      parotid lesions.
AB  - BACKGROUND/AIM: Human papillomavirus (HPV) is implicated in head and neck
      squamous cell carcinomas. However, the causal role of HPV in carcinomas of the
      parotid gland remains uncertain and less documented. This study aimed to
      determine the potential implication of HPV in the development of benign and
      malignant lesions of the parotid gland. MATERIALS AND METHODS: Paraffin-embedded
      biopsies were obtained from 40 patients with benign parotid gland tumors and from
      39 patients with parotid gland carcinomas. The 79 samples were evaluated for the
      presence of HPV DNA using both GP5+/GP6+ consensus Polymerase Chain Reaction
      (PCR) and type-specific E6/E7 PCR to detect 18 HPV types. RESULTS: Our results
      showed a low prevalence of HPV, with only three HPV-positive cases among the 40
      benign tumors and one infected carcinoma in the malignant population. CONCLUSION:
      No association between the presence of HPV DNA and the development of parotid
      gland tumors was found in our study.

PMID- 22993340
TI  - Compliance, analgesic use and side-effect protection within a German cohort of
      the TEAM trial.
AB  - BACKGROUND: Compliance is an essential aspect for the success of any medical
      intervention. Adverse events (AEs) contribute significantly to non-compliance
      with endocrine treatment. The Tamoxifen Exemestane Adjuvant Multinational (TEAM)
      trial compared five years of adjuvant exemestane therapy with the sequence of
      tamoxifen followed by exemestane. PATIENTS AND METHODS: A retrospective analysis
      of the German cohort of TEAM was conducted to determine the effects of prior
      tamoxifen on the tolerability profile of exemestane in both treatment arms.
      RESULTS: Fracture incidence was significantly higher during the first 30 months
      of exemestane versus the 30 months of exemestane following tamoxifen for 2-3
      years; however, the incidence of AEs was not significantly different. With regard
      to compliance, the use of analgesics did not influence overall or disease-free
      survival (DFS) nor the incidence of distant recurrence in both treatment groups.
      CONCLUSION: Tamoxifen has a boneprotective effect when applied before exemestane
      treatment. Intake of analgesics (or pain medication) does not influence
      compliance or treatment outcome.

PMID- 22993341
TI  - A randomized controlled non-inferiority study comparing the antiemetic effect
      between intravenous granisetron and oral azasetron based on estimated 5-HT3
      receptor occupancy.
AB  - BACKGROUND: The acute antiemetic effect was compared between oral azasetron and
      intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor
      occupancy theory. PATIENTS AND METHODS: Receptor occupancy was estimated from
      reported data on plasma concentrations and affinity constants to 5-HT(3)
      receptor. A randomized non-inferiority study comparing acute antiemetic effects
      between oral azasetron and intravenous granisetron was performed in 105 patients
      receiving the first course of carboplatin-based chemotherapy for lung cancer.
      RESULTS: Azasetron exhibited the highest 5-HT(3) receptor occupancy among various
      first-generation 5-HT(3) antagonists. The complete response to oral azasetron was
      shown to be non-inferior to that of intravenous granisetron, in which the risk
      difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit
      of the confidence intervals did not exceed the negative non-inferiority margin (
      0.1). The complete response during the overall period was not different (68%
      versus 67%). CONCLUSION: Oral azasetron was found to be non-inferior to
      intravenous granisetron in the acute antiemetic effect against moderately
      emetogenic chemotherapy.

PMID- 22993342
TI  - Combining paclitaxel and lapatinib as second-line treatment for patients with
      metastatic transitional cell carcinoma: a case series.
AB  - BACKGROUND: Current first-line cisplatin-based combination chemotherapy regimens
      provide interesting response rates but limited impact on survival for patients
      with metastatic transitional cell carcinoma of the urothelium. Such results leave
      a significant patient population in need of salvage therapy. PATIENTS AND
      METHODS: As the epidermal growth factor receptors 1 and 2 (EGFR and HER2) are
      frequently overexpressed in urothelial carcinoma, we explored the feasibility of
      a combination of paclitaxel (80 mg/m(2)/week) and lapatinib (1,500 mg orally
      daily) for six patients who were treated after failure of first-line platinum
      based chemotherapy. RESULTS: Only one out of six patients was able to receive the
      full doses during the first six weeks of treatment, while grade 2 or 3 diarrhea
      events required lapatinib dose reduction (one patient) or discontinuation (five
      patients), despite loperamide support. CONCLUSION: This combination is not
      recommended for this population of patients.

PMID- 22993343
TI  - Prediction of recurrence after complete resection in patients with NSCLC.
AB  - A proportion of lung cancer patients develop recurrence, even after curative
      resection. This study reviewed the literature, focusing on the key words:
      recurrence, relapse, relapse-free survival, disease-free survival (DFS), surgery,
      and non-small cell lung cancer (NSCLC), not overall survival (OS) to evaluate the
      post-operative risk factors for tumor recurrence after surgery. This article
      reviews the current status and progress on this subject.

PMID- 22993344
TI  - Solitary liver lesions of indeterminate malignancy--outcome following surgical
      resection.
AB  - BACKGROUND: Well-differentiated hepatocellular carcinoma (HCC) may resemble
      benign liver lesions on initial diagnostic work-up. The validity of surgical
      resection for preoperatively unclear liver lesions was investigated in this
      study. PATIENTS AND METHODS: We conducted a retrospective analysis of 483
      patients subjected to liver resection over a 15-year period. RESULTS: Forty-five
      patients (9%) were considered to have presented with indeterminate solitary
      lesions. There were 18 cases of HCC (40%) and 27 cases (60%) of benign lesions,
      most commonly focal nodular hyperplasia (n=18). Patients with HCC had a higher
      median age as compared to patients with benign pathology (67 vs. 55 years;
      p=0.002) and the median tumor size was larger (85 vs. 30 mm; p=0.007). Major
      complications (Clavien grade III or higher) occurred in three cases (7%) and
      there was no in-hospital mortality. CONCLUSION: The results favor an aggressive
      approach, i.e. surgical intervention, to patients presenting with indeterminate
      solitary liver tumors due to the high likelihood of an underlying HCC.

PMID- 22993345
TI  - Expression of p53 and Ki-67 as prognostic factors for survival of men with
      colorectal cancer.
AB  - In patients with colorectal cancer (CRC) several independent prognostic factors
      are well-supported in the literature, including TNM stage, histological type and
      grade, and serum levels of carcinoembryonic antigen (CEA). All cancer cells
      express high levels of tissue proliferation markers, such as Ki-67 and p53, which
      are currently considered prognostic markers for patients with several types of
      cancers. We retrospectively studied 31 men (median age 65, range 48-75 years)
      with confirmed Dukes' B colorectal adenocarcinoma. The following parameters were
      recorded: age of the patients (years), baseline CEA serum levels (ng/ml), Ki-67
      and p53 expression (%), and survival (months). The mean overall survival was 37.3
      +/- 13.7 months. The mean baseline CEA serum level was 79 +/- 7.4 ng/ml, while
      the percentage positivity for Ki-67 and p53 in cancer tissues was 46.9 +/- 19.2
      and 48.7 +/- 14.2, respectively. There was a significant correlation between Ki
      67 and p53 expression (R=0.82, p<0.001) and an inverse relationship between
      survival and the expression of both Ki-67 (R=-0.67, p<0.001) and p53 (R=-0.64,
      p<0.001). No significant correlation was found between survival and age (R=0.22,
      p=0.22) or CEA (R=0.08, p=0.67). There was no relationship between CEA and age
      (R=0.34, p=0.06), Ki-67 (R=-0.021, p=0.90) or p53 (R=0.03, p=0.87). In
      conclusion, our preliminary results showed that both Ki-67 and p53 overexpression
      in CRC are associated with a worse outcome. In this selected group of patients,
      these prognostic markers were independent of age, and the preoperative CEA serum
      levels did not have any relationship with survival.

PMID- 22993347
TI  - Association of syndecan-1 with angiogenesis-related markers, extracellular matrix
      components, and clinicopathological features in colorectal carcinoma.
AB  - Syndecan-1 is a transmembrane heparansulfate proteoglycan, which regulates cell
      proliferation, migration, angiogenesis, cell-to-cell and cell-to-extracellular
      matrix adhesion and may influence malignant cell behavior. We investigated the
      alterations of syndecan-1 expression in colorectal cancer and analyzed the
      relationship between clinicopathological parameters, proliferation indices,
      angiogenic markers, and extracellular matrix components. Syndecan-1 protein
      expression observed in the tumorous epithelium was high in 52/97 (53.6%) of the
      studied cases, moderate in 20/97 (20.6%), and weak in 5/97 (5.22%) of the cases,
      and there was strong stromal expression in 34.02% of the tumors. Syndecan-1
      expression was statistically correlated to VEGF expression in tumor (p=0.001) and
      vessels (p=0.007). In addition, there was a borderline correlation between
      syndecan-1 expression and tenascin (p=0.053). Patients with weak staining
      reaction had a more unfavorable prognosis (p=0.032) in univariate analysis. These
      results indicate the implication of syndecan-1 in the remodeling and angiogenesis
      of colorectal cancer tissue, through interaction with other extracellular matrix
      components and VEGF, probably influencing the tumor progression and
      aggressiveness.

PMID- 22993346
TI  - Health-related quality of life during sequential chemotherapy with carboplatin
      followed by weekly paclitaxel in advanced ovarian cancer: a multicenter phase ii
      study of the North Eastern German Society of Gynecological Oncology.
AB  - AIM: We describe the impact of a sequential dose-dense schedule of carboplatin
      and paclitaxel on the quality of life (QoL) of patients with ovarian cancer.
      PATIENTS AND METHODS: In this multicenter phase II trial, four cycles of
      carboplatin followed by 12 cycles of weekly paclitaxel were applied after
      cytoreductive surgery. QoL was assessed using the QoL questionnaires EORTC QLQ
      C30 and QLQ-OV28 before chemotherapy (baseline), after four cycles of
      carboplatin, at the end of treatment (EOT), and after 6, 12, and 24 months.
      RESULTS: Out of 104 eligible patients 87 (84%) participated in at least one QoL
      assessment. At baseline, all QLQ-C30 scales and symptoms were significantly worse
      than age-adjusted values for the general population. Subsequently QoL improved in
      general. During chemotherapy with paclitaxel, most functioning scales and
      symptoms worsened slightly (not significantly). However, peripheral neuropathy
      and chemotherapy-related side-effects increased to clinically important levels.
      At the end of treatment, most QoL scores were similar to those of the general
      population, but physical functioning and fatigue were worse. Sexual functioning
      and peripheral neuropathy remained problematic. CONCLUSION: QoL was affected
      mainly by the weekly paclitaxel schedule, but effects were in most cases only
      temporary. A dose-dense regimen using a sequential protocol may be favourable in
      terms of QoL.

PMID- 22993348
TI  - High nuclear protein kinase CbetaII expression is a marker of disease recurrence
      in oral squamous cell carcinoma.
AB  - BACKGROUND: Protein kinase C beta II (PKCbetaII) is a member of the family of
      serine/threonine kinases which are involved in tumor formation and progression.
      This study investigated the significance of PKCbetaII in oral squamous cell
      carcinoma (OSCC). PATIENTS AND METHODS: The expression of PKCbetaII was
      determined in tumors from 59 patients with OSCC using immunohistochemistry and
      was correlated with patients' clinical characteristics and outcomes. RESULTS:
      Twenty-six cases (44%) exhibited nuclear PKCbetaII staining. High nuclear
      PKCbetaII expression was significantly associated with the consumption of betel
      quid (p=0.015) and alcohol (p=0.024) in OSCC. Kaplan-Meier analysis revealed a
      shorter time-to-recurrence in patients with high nuclear PKCbetaII expression
      (p=0.018). In multivariate analysis for recurrence, high nuclear staining of
      PKCbetaII remained an independent adverse prognostic factor (hazard ratio=2.3,
      p=0.016). CONCLUSION: The present study provides evidence of the potential
      prognostic value of PKCbetaII analysis in OSCC.

PMID- 22993349
TI  - The expression of beta-microseminoprotein but not CRISP3 is reduced in ovarian
      cancer and correlates to survival.
AB  - BACKGROUND: beta-Microseminoprotein (MSMB) is an abundant protein in seminal
      plasma. Most of it is present as a free protein but a small part is bound to
      cysteine-rich secretory protein 3 (CRISP3) as a non-covalent complex. Even though
      their physiological function is unknown, both MSMB and CRISP3 have been ascribed
      roles in prostate carcinogenesis. Thus, several recent experimental studies
      indicate a tumor-suppressor role for MSMB. The present study was undertaken in
      order to evaluate, for the first time, the expression of MSMB and CRISP3 in
      ovaries and in ovarian tumors and to determine if their expression might indicate
      a role in ovarian tumor development. MATERIALS AND METHODS: Biopsies from
      prospectively collected samples from ovaries and benign, borderline and invasive
      ovarian tumors were analyzed for expression of MSMB and CRISP3 by
      immunohistochemistry. In patients with ovarian cancer the expression was compared
      to survival. RESULTS: Both MSMB and CRISP3 were strongly stained in ovarian
      epithelial cells and weakly stained in the stroma. In ovarian blood vessels,
      CRISP3 exhibited strong to medium staining, while MSMB was only weakly expressed.
      In benign and borderline tumors the staining pattern was similar to the one
      observed in the ovaries. In invasive neoplasms, the expression of MSMB in the
      tumor cells was significantly reduced. In univariate analysis, decreased
      expression of MSMB correlated to reduced survival. No correlation was found with
      stage, the strongest prognostic indicator for ovarian cancer, which supports an
      independent role of MSMB in ovarian carcinogenesis. For CRISP3, a staining
      pattern comparable to that for MSMB was observed in all groups, except the fact
      that decreased expression was not observed in invasive tumor cells. CONCLUSION:
      MSMB and CRISP3 were widely distributed in ovaries and in ovarian tumors; the
      expression of MSMB fits well with a tumor-suppressor function in ovarian
      carcinogenesis.

PMID- 22993350
TI  - A review of dose-dense temozolomide alone and in combination with bevacizumab in
      patients with first relapse of glioblastoma.
AB  - Treatment of patients with glioblastoma improved dramatically when concomitant
      and adjuvant temozolomide was added to external radiation therapy. The addition
      of this new treatment schedule as well as the improvements in individually
      tailored radiation treatment, has resulted in a larger proportion of patients
      being fit for further treatment after first relapse. One of the most interesting
      combinations that have started to become part of the therapeutic arsenal in the
      daily clinic is dose-dense temozolomide in combination with bevacizumab. We
      reviewed and compiled the literature concerning the present topic based on a
      search of the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) for the years
      between 1995 and 2011. The clinical studies that have been performed are small
      and divergent, making it difficult to grade the scientific evidence for the
      combinatorial treatment of dose-dense temozolomide and bevacizumab. However, the
      available studies and the experience we have at our departments suggest that this
      combination is of interest for glioblastoma patients experiencing first relapse.
      More randomized clinical trials are needed in order to establish the standard of
      treatment at first relapse in patients with glioblastoma.

PMID- 22993351
TI  - The role of cetuximab in the treatment of metastatic colorectal cancer.
AB  - Targeted biological therapy is becoming a standard in personalized medicine for
      patients with advanced stages of cancer. Treatment with cetuximab, an anti
      epidermal growth factor receptor (EGFR) antibody, represents an example of
      personalized anticancer therapy for patients with metastatic colorectal cancer
      and wild (non-mutated) type of the Kirsten rat sarcoma viral oncogene (KRAS).
      Here the role of cetuximab in treating metastatic colorectal cancer is discussed
      with a focus on the treatment of hepatic metastases.

PMID- 22993352
TI  - Hyperfractionated radiotherapy with concurrent docetaxel for advanced head and
      neck cancer: a phase II study.
AB  - AIM: To evaluate the value of hyperfractionated radiotherapy with concurrent use
      of low-dose docetaxel in locally-advanced head and neck squamous cell cancer
      (HNSCC). PATIENTS AND METHODS: Patients eligible for this study had confirmed
      diagnosis of HNSCC stages II (>10 cm(3)) to IVB. Radiotherapy was delivered twice
      daily at 1.2 Gy/fraction to a total dose of 72.0 Gy. Docetaxel (10 mg/m(2)) was
      administered weekly during radiotherapy. RESULTS: From March 2003 to October
      2008, 70 patients were treated. Primary sites included the oropharynx (n=25),
      hypopharynx (n=24), larynx (n=18), and other sites (n=3). Major grade 3 acute
      toxicities included mucositis (n=43) and treatment-related pain (n=20). The
      median follow-up period for surviving patients was 43 months. The 5-year local
      control rate and overall survival rate were 62.6% and 61.6%, respectively.
      CONCLUSION: This modality is a valuable treatment option for the management of
      locally-advanced HNSCC.

PMID- 22993353
TI  - A phase I study of concurrent chemoradiotherapy and cetuximab for locally
      advanced esophageal cancer.
AB  - AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities
      (DLTs) of concurrent chemoradiotherapy and cetuximab in patients with non
      resectable locally advanced esophageal cancer. PATIENTS AND METHODS: Escalating
      doses of oxaliplatin every second week and daily tegafur/uracil were given
      concurrently with radiotherapy, 59.4 Gy in 33 fractions. Cetuximab was given on
      day 15 (400 mg/m(2)) and weekly (250 mg/m(2)) during radiotherapy. Fixed doses of
      oxaliplatin (130 mg/m(2)) and tegafur/uracil (300 mg/m(2)) were administered
      before, and after radiotherapy. RESULTS: Eleven patients were included in the
      study; two were excluded due to allergic reactions to cetuximab. In DL2
      (tegafur/uracil 300 mg/m(2), oxaliplatin 30 mg/m(2)) two grade 3/4 fistula and
      one grade 3 neuropathy were observed. Six patients were enrolled in DL1
      (tegafur/uracil 150 mg/m(2)/, oxaliplatin 30 mg/m(2)) with no DLTs. Four out of 9
      patients had complete response. CONCLUSION: Concomitant chemoradiotherapy and
      cetuximab had significant activity. DL1 was established as the MTD.

PMID- 22993354
TI  - Role of conservative (palliative) care-only in the management of advanced
      malignant pleural mesothelioma.
AB  - Despite new aggressive therapeutical options for advanced malignant pleural
      mesothelioma (MPM), benefits to survival remain limited. Moreover, deleterious
      effects of high-dose chemotherapy and aggressive surgery are well-known. Outcomes
      of untreated patients are usually not reported, and whether a treatment can be
      delayed or avoided is still an open question. We discuss here two clinical cases
      and with conservative (palliative) management alone for advanced MPM [corrected].

PMID- 22993355
TI  - Salvage chemotherapy using gemcitabine for taxane/platinum-resistant recurrent
      ovarian cancer: a single institutional experience.
AB  - BACKGROUND: The purpose of this study was to report on the safety and efficacy of
      gemcitabine used as salvage chemotherapy for ovarian cancer. PATIENTS AND
      METHODS: From January 2002 to October 2011, 27 patients were treated with
      gemcitabine for platinum-resistant recurrent ovarian cancer. Gemcitabine (800
      mg/m(2)) was given on days 1, 8, and 15 of every 28 days. The patients' medical
      records were retrospectively reviewed. RESULTS: All 27 patients had previously
      received paclitaxel/carboplatin doublet and their disease had become platinum
      resistant. The median number of previous chemotherapy regimens was 2 (range 1-7).
      A total of 114 cycles of single-agent gemcitabine were administered, with a
      median of 3 (range 1-10). No complete responses were observed. Partial response
      (PR) was observed in five patients (18.5%). Eight patients demonstrated stable
      disease (SD). The median duration of response for 5 responders was 4 months
      (range 2-6 months). The median survival time was 15 months. Patients with PR or
      SD (n=13) had significantly better survival compared with the group with
      progressive disease (n=14) (p=0.03, by univariate analysis). In addition,
      multivariate Cox proportional hazards analysis revealed that responses to
      gemcitabine were a significant factor for survival (hazard ratio=0.08, 95%
      confidence interval=0.0138 to 0.5614, p=0.01). Cases with hematological toxicity
      included 10 patients (37.0%) with grade 3/4 neutropenia, 3 patients (11.1%) with
      grade 3 thrombocytopenia, and 3 patients (11.1%) with grade 3 anemia. Non
      hematological toxicity was well-tolerated. CONCLUSION: Gemcitabine (800 mg/m(2))
      used for recurrent ovarian cancer possesses a modest activity and a well
      tolerated toxicity.

PMID- 22993356
TI  - Feasibility of concurrent chemoradiotherapy with S-1 administered on alternate
      days for elderly patients with head and neck cancer.
AB  - BACKGROUND: Concurrent chemoradiotherapy (CCRT) improves survival and organ
      preservation in patients with head and neck squamous cell carcinoma (HNSCC),
      compared with radiotherapy. However, such regimens are not always feasible
      because of substantial toxicities. Therefore, we evaluated the feasibility of S
      1, administered on alternate days, and concurrent radiotherapy among elderly
      patients with HNSCC. PATIENTS AND METHODS: Nineteen eligible patients were
      treated with CCRT. S-1 was administered at a dose of 80 mg/day on alternate days
      with the intention to reduce the toxicity. RESULTS: With a median follow-up
      period of 19.2 months, the two-year overall survival rates were 62.5% for
      patients with stage III disease and 50.0% for those with stage IV. The Complete
      Response (CR) rates were 100% for stage II and 66.7% for stage III/IV disease.
      Grade 3 mucositis occurred in three patients. Grade 3 or 4 hematological
      toxicities were not observed. CONCLUSION: CCRT with S-1 administered on alternate
      days was effective and well-tolerated among elderly patients with HNSCC.

PMID- 22993357
TI  - Stereotactic body radiation therapy for stage I non-small cell lung cancer
      patients with chronic respiratory insufficiency requiring domiciliary oxygen
      therapy.
AB  - BACKGROUND: The efficacy of stereotactic body radiation therapy (SBRT) for
      patients treated with domiciliary oxygen therapy is not well-known. PATIENTS AND
      METHODS: We collected the clinical records of 15 patients with chronic
      respiratory insufficiency requiring domiciliary oxygen therapy at 1-3 l/min who
      were treated with SBRT for stage I non-small cell lung cancer. All patients were
      fixed with a thermoplastic body cast system. SBRT was given in 7-8 fields with an
      isocenter dose of 40-60 Gy in 4-10 fractions (median, 48 Gy in 4 fractions).
      RESULTS: The overall 2-year and 5-year survival rates for all patients were 67.4%
      and 34.7%, while the disease-specific 2-year and 5-year survival rates were 90.0%
      and 72.0%, respectively. Pulmonary adverse effects were mild in the majority of
      the patients, although two patients had grade 2 radiation pneumonitis. The oxygen
      flow required increased slightly at follow-up periods greater than one year, but
      was still at an acceptable level. CONCLUSION: SBRT was feasible for patients
      requiring domiciliary oxygen therapy.

PMID- 22993358
TI  - Systemic inflammatory response predicts perioperative central venous catheter
      related bloodstream infection in patients Undergoing colorectal cancer surgery
      with administration of parenteral nutrition.
AB  - Our aim was to examine whether systemic inflammatory response (SIR) is associated
      with perioperative central venous catheter-related bloodstream infection (CVC
      RBSI) in patients undergoing surgery for colorectal cancer (CRC) with
      administration of parenteral nutrition (PN). Between May 2002 and August 2009,
      310 patients undergoing CRC surgery were enrolled. A CVC was inserted in all
      patients for administration of PN. Among these patients, 117 developed fever, and
      blood cultures for diagnosis of CVC-RBSI were obtained from them. A final total
      of 22 patients were diagnosed as having CVC-RBSI. Univariate analysis was
      performed to evaluate the risk factors for CVC-RBSI using the clinical
      characteristics of the patients. The results of univariate analyses revealed that
      only the Glasgow Prognostic Score was an independent risk factor for CVC-RBSI
      (odds ratio 3.733; 95% confidence interval 1.416-9.844; p=0.008). The Glasgow
      Prognostic Score is associated with CVC-RBSI in patients undergoing CRC surgery
      with administration of PN.

PMID- 22993359
TI  - A case of synchronous metastasis of breast cancer to stomach and colon.
AB  - A case of synchronous metastasis of breast cancer to the stomach and colon is
      reported. A 38-year-old woman with a history of bilateral breast cancer was
      admitted for endoscopic examination because of occult blood. Endoscopic
      examination showed elevated lesions on the mucosal surface of the stomach and
      cecum. Histopathological examination of the biopsy specimens obtained from both
      sites showed adenocarcinoma, comprised of tumor cells with structural and nuclear
      atypia, which were similar to those of the primary breast cancer cells. In
      immunohistochemical analysis, these tumor cells stained positive for ER.
      Therefore, we diagnosed a synchronous metastasis of breast cancer to the stomach
      and colon. Synchronous metastasis of breast cancer to the stomach and colon
      without liver metastasis or peritoneal dissemination is extremely rare, with only
      4 reported cases existing in literature.

PMID- 22993360
TI  - Carcinoma of the axillary tail of Spence: a case series.
AB  - There is sparse information about cancer in the axillary tail of Spence (CATS).
      Eight hundred and thirty-nine patients with breast cancer were retrospectively
      studied for the occurrence of CATS. Ten patients were identified based on
      detection by imaging studies. A tendency towards stage II or III disease, and
      estrogen and progesterone receptor-negative neoplasms in the older age (>45
      years) group was observed. Management by conservative or radical surgery, with or
      without postoperative radiotherapy and chemotherapy, effected an estimated five
      year disease-free survival rate of 67%, and rates of local failure, regional
      recurrence as well as distant metastasis of 0%, 10% and 30%, respectively. The
      treatment of CATS in accordance with modern day standards of care resulted in
      acceptable prognosis and disease control.

PMID- 22993361
TI  - Histological grade predicts for recurrence in patients with uterine endometrioid
      carcinoma without myometrial involvement.
AB  - AIM: To evaluate clinical outcomes and identify factors predictive for recurrence
      in patients with 1988 (FIGO) stage IA uterine endometrioid carcinoma. PATIENTS
      AND METHODS: Patients who underwent hysterectomy for stage IA carcinoma were
      identified in our database. Fisher's exact and chi(2) tests were used to identify
      factors that influenced outcome. Survival plots were generated according to
      Kaplan-Meier product-limit method and the log-rank test was used to determine
      significance. RESULTS: A total of 121 patients were identified. Eighty-seven
      percent (n=105) had tumor FIGO grade 1, 9% (n=11) grade 2, and 4% (n=5) grade 3
      tumors. Six patients (5%) experienced recurrence. The 5-year recurrence-free
      survival (RFS), disease-specific survival (DSS) and overall survival (OS) were
      93%, 95%, and 85%, respectively. On univariate analysis, tumor FIGO grade 2/3 was
      strongly associated with tumor recurrence (p=0.003), DSS (p=0.016), and OS
      (p=0.023). The 5-year RFS, DSS, and OS were 65.1%, 73.9%, and 63.9% respectively
      for patients with grade 2 and 3 tumors, which were significantly less than the
      corresponding rates of 97.5% (p <= 0.0001), 98.6% (p=0.001), and 87.7% (p=0.024)
      for patients with grade 1 tumors. CONCLUSION: In this large cohort of patients,
      RFS, DSS and OS were excellent. Patients with FIGO grade 2/3 tumors had worse
      outcomes compared to those with grade 1 tumors. Therefore, while most patients
      with stage IA disease do not need adjuvant treatment after hysterectomy, our
      results suggest that patients with higher-grade tumors have an increased
      likelihood for recurrence and they may benefit from counseling regarding adjuvant
      therapies.

PMID- 22993362
TI  - High levels of HMGB1 in plasma may be due to ex vivo cell necrosis.
AB  - BACKGROUND: High mobility group box 1 protein (HMGB1) is considered an important
      biological marker during inflammation and malignancies. Here, we evaluated sample
      handling and effects of ex vivo necrosis on HMGB1 levels. MATERIALS AND METHODS:
      Plasma samples were obtained from healthy volunteers (n=14) simulating the
      standard laboratory conditions, overnight incubations and harsh treatment. HMGB1
      levels were evaluated by ELISA or western blot. Additionally, levels of
      hemoglobin, hemolysis index and lactate dehydrogenase were measured. RESULTS:
      Plasma levels of HMGB1 were 9-fold increased in samples stored overnight at room
      temperature, as compared to those processed directly. The rapid centrifugation
      prevented the increase of HMGB1 in stored samples. Hemoglobin, hemolysis index
      and lactate dehydrogenase concentrations showed significant correlations with
      HMGB1 levels. CONCLUSION: Handling of blood samples is important for the accurate
      estimation of systemic HMGB1. We propose that all samples with high HMGB1
      concentrations should be evaluated for markers of ex vivo necrosis.

PMID- 22993363
TI  - A preliminary study of single intraperitoneal administration of paclitaxel
      followed by sequential systemic chemotherapy with S-1 plus paclitaxel for
      advanced gastric cancer with peritoneal metastasis.
AB  - AIM: A preliminary study with the aim of evaluating the safety and efficacy of a
      single intraperitoneal administration of paclitaxel, combined with intravenous
      administration of paclitaxel plus S-1, was carried out in gastric cancer patients
      with peritoneal metastasis. PATIENTS AND METHODS: Paclitaxel was administered
      intraperitoneally at 80 mg/m(2). After one to two weeks, S-1 was administered at
      80 mg/m(2)/day for 14 consecutive days, followed by seven days' rest. Paclitaxel
      was administered intravenously at 50 mg/m(2) on days 1 and 8. The safety,
      pharmacokinetic analysis and efficacy of this therapy were investigated. RESULTS:
      Fifteen patients were enrolled in this study. The toxic effects of the
      intraperitoneal chemotherapy were mild. The toxic effects with the systemic
      chemotherapy were acceptable. The ratio of (AUC peri)/(AUC pla) was 1065:1 in the
      pharmacokinetic analysis. The one-year overall survival rate was 10/15 (66.7%).
      CONCLUSION: A single intraperitoneal administration of paclitaxel combined with
      intravenous administration of paclitaxel plus S-1 is a well-tolerated and
      feasible treatment for patients with gastric cancer with peritoneal metastasis.

PMID- 22993364
TI  - Carotid intima-media thickness and laboratory parameters of atherosclerosis risk
      in patients with breast cancer.
AB  - AIM: To investigate the relation between intima-media thickness (IMT) and
      laboratory parameters of atherosclerosis risk in patients with breast carcinoma.
      PATIENTS AND METHODS: IMT and a panel of laboratory parameters associated with
      the risk of atherosclerosis were studied in 192 patients with histologically
      verified breast carcinoma. RESULTS: Patients with metastatic disease had
      significantly higher fibrinogen, C-reactive protein (CRP), urinary neopterin and
      mean IMT, and significantly lower serum albumin and hemoglobin concentrations.
      Significant correlations were observed between CRP, urinary neopterin, mean IMT
      and other parameters of cardiovascular risk. Age was an independent predictor of
      the presence of sonographic signs of atherosclerosis using logistic regression,
      and age, glucose, time from start of chemotherapy, high-density lipoprotein
      cholesterol, D-dimers were independently associated with IMT in stepwise
      regression models. CONCLUSION: In addition to the associations between IMT and
      laboratory or clinical parameters of the risk of atherosclerosis, IMT may also be
      associated with the time from chemotherapy.

PMID- 22993365
TI  - Treatment decision-making processes in the systemic treatment of ovarian cancer:
      review of the scientific evidence.
AB  - BACKGROUND: The systemic treatment of epithelial ovarian cancer (OC) is one of
      the cornerstones in the multimodal management of advanced OC in both primary and
      recurrent stages of this disease. In most situations various treatment options
      are available but only few data exists about the treatment decision-making
      process. Therefore, we conducted a review of the current literature regarding the
      decision-making process concerning the systemic therapy in patients with advanced
      ovarian cancer. MATERIALS AND METHODS: The electronic database MEDLINE (PubMed)
      was systematically reviewed for studies that evaluate the treatment decision
      making processes in patients with advanced OC. RESULTS: The PubMed database was
      searched in detail for all titles and abstracts of potentially relevant studies
      published between 1995 and 2011. An initial search identified 15 potentially
      relevant studies, but only seven met all inclusion criteria. Factors that
      influence treatment decisions in patients with OC include not only rational
      arguments and medical reasons, but also individual attitudes, fears, existential
      questions, various projections resulting from the physician patient relationship
      and the social environment. The physician's personal experience with OC treatment
      seems to be an important factor, followed by previous personal experience with
      medical issues, and the fear of side-effects and future metastases. Family and
      self-support organisations also seem to play a significant role in the treatment
      decision-making process. CONCLUSION: This review underlines the need for more
      research activities to explore the treatment decision-making process to enable
      the best individual support for patients in treatment decision-making. It is a
      challenge for clinicians to determine the individual information needs of women
      with OC and to involve them during the decision-making process to the extent they
      wish.

PMID- 22993366
TI  - Down-regulated expression of ATG5 in colorectal cancer.
AB  - The role of autophagy in tumor development is paradoxical. Although some genetic
      evidence has indicated that autophagy has as a tumor suppressor function, it also
      provides some advantages to tumors under metabolic stress conditions. Autophagy
      is regulated by several autophagy-related gene (ATG) proteins. In mammals, 16
      different ATG genes have been identified. To investigate the clinicopathological
      role of ATG5 in colorectal cancer, we firstly investigated its expression in
      patients with sporadic colorectal cancer. Expression analysis revealed ATG5 to be
      strongly down-regulated in colorectal cancer (38/40 patients). Interestingly,
      immunohistochemical analysis of colorectal cancer tissues indicated that
      increased ATG5 expression is associated with lymphovascular invasion (p=0.035).
      The findings in our limited clinical cohort indicate that ATG5 could be a
      potential prognostic or diagnostic biomarker.

PMID- 22993367
TI  - Colon neoplastic cells do not originate from bone marrow-derived cells after sex
      mismatched bone marrow transplantation.
AB  - BACKGROUND: Although previous studies indicate that gastrointestinal (GI) cancer
      may originate from cells recruited from bone marrow (BM) in mice, whether similar
      phenomena occur in humans is controversial. In the current study, we evaluated
      two female patients who developed colonic adenocarcinoma more than 10 years after
      gender-mismatched BM transplantation, and followingly underwent successful
      endoscopic mucosal resection. MATERIALS AND METHODS: Fluorescent in situ
      hybridization (FISH) analysis was used to determine whether the tumours contained
      donor-derived BM cells. RESULTS: Approximately 1.2% of the tumour cells contained
      Y-chromosome-positive signals, and a comparable percentage of normal colonic
      epithelial cells close to the tumour also contained Y-chromosome-positive
      signals. CONCLUSION: These results do not support the concept that GI cancer can
      originate from BM-derived cells.

PMID- 22993369
TI  - Cyclooxygenase-2 (COX-2) up-regulation is a prognostic marker for poor clinical
      outcome of upper tract urothelial cancer.
AB  - BACKGROUND: There are no reliable biomarkers for diagnosis, prediction of outcome
      or treatment effect monitoring for upper tract urothelial carcinoma (UTUC), which
      is a uniquely prevalent cancer in Taiwan. In the present study, 128 primary UTUC
      specimens of various grades and primary tumor status were examined for the
      expression of cyclooxygenase-2 (COX-2) in tumor and stroma tissues aiming to
      clarify the association of COX-2 expression with clinical outcomes in Taiwanese
      patients with UTUC. MATERIALS AND METHODS: Immunohistochemistry was implemented
      to investigate COX-2 expression levels in 128 paired tumor and stroma specimens.
      The association of COX-2 expression with tumor progression and prognosis was
      analyzed. RESULTS: Our data demonstrated that positive COX-2 expression was more
      frequent in stromal cells (57.0%), than in tumor sites (53.1%), and the up
      regulation of COX-2 was strongly associated with higher cancer-specific death and
      cancer recurrence rates. In COX-2-negative cases, no similar correlation was
      found. CONCLUSION: COX-2 expression was up-regulated in both stromal and tumor
      cells of more than half of the studied UTUC patients and the positive expression
      of COX-2 in stromal cells may be a potential predictive and prognostic biomarker
      for UTUC, especially for cancer-specific death and recurrence.

PMID- 22993368
TI  - Rapid relapse after resection of a sunitinib-resistant gastrointestinal stromal
      tumor harboring a secondary mutation in exon 13 of the c-KIT gene.
AB  - We describe a case with rapid relapse after resection of a sunitinib-resistant
      gastrointestinal stromal tumor (GIST). Liver metastases and foci of left
      retroperitoneal recurrence developed during adjuvant imatinib treatment. The
      tumors did not shrink after sunitinib treatment, and hepatectomy and
      retroperitoneal tumorectomy were performed. Histological examination showed a
      Ki67 labeling index of over 50% in viable tumor cells. Genomic analysis revealed
      mutations in exons 11 and 13 of the c-KIT gene. Computed-tomographic scan
      revealed retroperitoneal recurrence at the surgical site five weeks post
      operatively. In this case, high proliferative activity of the recurrent foci was
      associated with resistance to sunitinib and rapid recurrence during the
      perioperative withdrawal of sunitinib. It is important to consider the
      possibility of an exon 13 mutation with an aggressive phenotype when treating
      sunitinib-resistant GISTs. Surgical intervention for sunitinib-resistant GISTs
      should be carefully considered if R0 resection is not possible.

PMID- 22993370
TI  - Lenalidomide-associated hepatotoxicity--a case report and literature review.
AB  - BACKGROUND: Lenalidomide is an immunomodulatory drug frequently used for
      treatment of patients with multiple myeloma and myelodysplastic syndromes. This
      report presents a rare case of lenalidomide-associated hepatotoxicity and reviews
      the available literature. CASE REPORT: A 67-year-old male with multiple myeloma
      was hospitalized with nausea, vomiting and jaundice, while treated with a second
      three-week course of lenalidomide. The patient was found to have acutely elevated
      bilirubin, alkaline phosphatase, AST and ALT. He also had acute on chronic renal
      function impairment. Serology for viral hepatitis, abdominal ultrasound, magnetic
      resonance cholangiopancreatography and hepatobiliary scan revealed no
      abnormalities. Lenalidomide was stopped, resulting in subsequent (8 days)
      clinical improvement and normalization of the liver abnormalities. The RUCAM
      causality assessment score was 8, consistent with probable lenalidomide
      associated hepatotoxicity. Literature review revealed four other published cases
      of lenalidomide-associated hepatotoxicity with clinical presentation varying
      between cholestatic-, hepatocellular- or mixed-pattern of liver injury. All
      patients had clinical and laboratory improvement soon after lenalidomide
      discontinuation. Renal function impairment was present in 3 of the 5 reported
      cases. The exact mechanism of lenalidomide-associated liver injury remains
      unclear as only 2 patients had liver biopsies without specific findings.
      CONCLUSION: Physicians should be aware of the potential for lenalidomide
      associated hepatotoxicity, particularly in patients with underlying renal
      insufficiency.

PMID- 22993371
TI  - Hepatic arterial thrombosis: a critical complication during combination therapy
      of arterial chemoinfusion and sorafenib.
AB  - Hepatic arterial infusion chemotherapy (HAIC) combined with sorafenib is
      considered to be a promising therapeutic strategy for patients with advanced
      hepatocellular carcinoma. However, this combination therapy carries the risk of
      hepatic arterial thrombosis (HAT), which interrupts the continuation of HAIC, due
      to the side-effects of sorafenib. This case demonstrates a complication of HAT
      which occurred during HAIC combined with sorafenib. HAT was detected early by
      angiography via an implantable port-catheter system and was successfully treated
      with catheter-directed thrombolysis.

PMID- 22993372
TI  - Influcence of localization of primary tumor on effectiveness of 5
      fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) in
      patients with metastatic pancreatic adenocarcinoma: a retrospective study.
AB  - BACKGROUND: Metastatic pancreatic carcinoma is an incurable disease and
      gemcitabine remains the standard of care in first-line chemotherapy. Recently,
      fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX)
      demonstrated their superiority in first-line therapy. The objective of this study
      was to determine the efficacy of FOLFIRINOX in either first- and second-line
      treatment and to compare its efficacy in regard to the location of the primary
      tumor. PATIENTS AND METHODS: We performed a retrospective analysis of clinical
      factors associated with patients' survival using a cohort of 42 patients treated
      by FOLFIRINOX in either first- or second-line (2006-2011) and a control cohort of
      42 patients matched on sex and age without FOLFIRINOX treatment was obtained from
      a previous period of time (2001-2005). RESULTS: The median follow-up was 10
      months. The median overall survival was 10 months for the whole cohort and 10 and
      12 months for patients treated at first- and second-line, respectively (p<0.05).
      In this cohort using a multivariate model, among classical prognosis factors,
      only primary location in the head was associated with poor outcome. The median
      overall survival was 8 months for patients with primary location in the head and
      14 months for patients with primary location in the corpse or tail (p=0.02). In
      the gemcitabine cohort, the median follow-up was 8 months. Using a multivariate
      model, only performance status was associated with outcome. The median overall
      survival was 9 versus 6.5 months for patients with tumor, of the head versus tail
      or corpse tumor respectively (p<0.05). CONCLUSION: This retrospective study
      suggests the same efficacy of FOLFIRINOX used either in first- or second- line
      therapy for pancreatic cancer. Importantly, FOLFIRINOX compared favorably to
      gemcitabine only for patients with tumor of the corpse or tail. Further
      prospective trials are warranted to evaluate the efficacy of FOLFIRINOX in
      patients with tumor of the head of the pancreas.

PMID- 22993373
TI  - Feasibility study of zoledronic acid plus cisplatin-docetaxel as first-line
      treatment for advanced non-small cell lung cancer with bone metastases.
AB  - BACKGROUND: This study evaluated the safety and efficacy of combined zoledronic
      acid, cisplatin and docetaxel in patients with non-small cell lung cancer (NSCLC)
      with bone metastases. PATIENTS AND METHODS: Cisplatin 80 mg/m(2) and docetaxel 60
      mg/m(2) with zoledronic acid 4 mg were given intravenously on day 1 every 3-4
      weeks. The primary endpoint was feasibility of concomitant administration of
      zoledronic acid and cisplatin. RESULTS: Thirty-five chemonaive patients were
      enrolled. The median number of treatment cycles was four, and two or more cycles
      were administered in 29 (83%) patients without severe toxicity. No grade 3 or 4
      renal toxicity was observed. The objective response rate was 29% and the 1-year
      survival rate was 37%. The pain score improved in 77% of the patients after six
      weeks. CONCLUSION: The combination of zoledronic acid, cisplatin and docetaxel is
      well-tolerated with acceptable renal toxicity, and has modest activity as a first
      line treatment of NSCLC patients with bone metastases.

PMID- 22993374
TI  - HE4 and ROMA index in Czech postmenopausal women.
AB  - AIM: The first aim of the project was to evaluate the benefits of the
      determination of human epididymis protein 4 (HE4) and the risk of ovarian
      malignancy algorithm (ROMA) index for primary detection of ovarian cancer in a
      population of Czech women. The second aim was to study the advantages HE4, cancer
      antigen 125 (CA125) and ROMA index for distinguishing between benign and
      malignant tumors. Aware of the age distribution of ovarian cancer, we focused on
      postmenopausal patients. PATIENTS AND METHODS: Our group of patients consisted of
      256 females, 21 with ovarian cancer and 235 with benign ovarian tumors. All
      diagnoses were histologically verified. We determined the serum levels of HE4 and
      CA125 and calculated the ROMA2 index for postmenopausal women. Serum levels of
      the analytes were measured using an Architect 1000i instrument. Serum samples
      were collected prior to surgery or any other form of treatment and the results of
      the two groups of patients were compared (malignant vs. benign). RESULTS: There
      was a significant difference in the serum levels for all parameters studied
      between the groups of patients with malignant and those with benign diagnoses
      (Wilcoxon test, p<0.0001). When all parameters were evaluated at 95% specificity,
      the HE4 cut-off was 112 pmol/l at a sensitivity of 71.42%, a positive predictive
      value (PPV) of 55.56%, a negative predictive value (NPV) of 97.14% and an area
      under the curve (AUC) of 0.9152. The CA125 cut-off was 81 IU/l at a sensitivity
      of 80.95%, a PPV of 58.62%, a NPV of 98.23% and an AUC of 0.9731. ROMA2 index had
      a cut-off 37.70% at a sensitivity of 85.71%, a PPV of 62.06%, a NPV of 98.65% and
      an AUC of 0.9803. The highest diagnostic efficiency was achieved by the ROMA2
      index. CONCLUSION: Determination of HE4 along with CA125 and ROMA2 index
      calculation is a suitable method for the improvement of the primary detection of
      ovarian cancer. This approach also improves the differential diagnostic
      possibilities for distinguishing between malignant and benign tumors.

PMID- 22993375
TI  - Large loop excision of the transformation zone and cervical intraepithelial
      neoplasia: a 22-year experience.
AB  - AIM: To review the 22-year experience of the use of large loop excision of the
      transformation zone (LLETZ) for the treatment of cervical intraepithelial
      neoplasia (CIN). MATERIALS AND METHODS:  DESIGN: Retrospective observational
      study. SETTING: University Hospital of Ioannina, Greece. PERIOD: January 1989
      until December 2011. POPULATION: Women undergoing excisional treatment with LLETZ
      for CIN. Women with invasive disease were excluded. INTERVENTION: Excisional
      treatment with LLETZ. Women had post-operative surveillance with cytology and
      colposcopy at 6, 12, 18 and 24 months, and yearly thereafter. OUTCOMES: We
      assessed the histological outcomes and margin involvement, as well as the rate of
      treatment failures requiring a repeat conization. RESULTS: A total of 3861 LLETZ
      biopsies were recorded during the study period. The histological evaluation of
      the cone specimens showed CIN1 in 897 (23.2%), CIN2 in 1129 (29.3%), CIN3 in 1322
      (34.2%), microinvasive disease in 158 (4.1%), HPV lesions in 206 (5.3%) and
      normal histological findings in 149 (3.9%) women. The margins were reported as
      clear in 3166 (82%) cases, involved in 437 (11.3%) cases and uncertain in 258
      (6.7%) cases. A total of 239 (6.2%) women underwent a second conization due to
      treatment failure. CONCLUSION: LLETZ remains the most popular conservative
      technique of treatment for women with precancerous cervical lesions. Post
      treatment surveillance of these women is essential in order to detect residual or
      recurrent disease. New HPV biomarkers, introduced over the last two years, appear
      to be useful in the follow-up after treatment. A scoring system may allow for
      accurate prediction of women at risk of treatment failure and for tailored post
      treatment surveillance.

PMID- 22993376
TI  - Gemcitabine-induced pulmonary toxicity.
AB  - BACKGROUND: Gemcitabine is the only approved cytotoxic agent for the treatment of
      pancreatic cancer by the Food and Drug Administration. In addition, gemcitabine
      is also commonly used for the management of breast, ovarian, and non-small cell
      lung cancer. Myelosuppression is the most common toxicity of gemcitabine therapy.
      Pulmonary toxicities due to gemcitabine have, however, been reported. Dyspnea
      occurs in approximately 25% of patients treated with gemcitabine, whereas serious
      pulmonary toxicities are much less common, approximately 0.3%. Here, we present a
      case of gemcitabine-induced pneumonitis, encountered during treatment of
      pancreatic cancer, and review the literature of this rare, but dangerous
      complication. CASE REPORT: A 56-year old male being treated for stage IV
      pancreatic cancer developed progressive dyspnea on exertion, chest tightness, and
      palpitations. Oxygen saturation was 82-84%. Computerized-tomography (CT)
      angiography of the chest demonstrated new diffuse groundglass opacities in the
      bilateral lower lobes when compared to the CT of the chest without intravenous
      contrast, 5 weeks prior. Mild to moderate emphysema was also seen, but no
      pulmonary emboli were detected. Myocardial infraction was ruled-out by normal
      electrocardiogram and normal cardiac biomarkers. CONCLUSION: We report another
      case of gemcitabine-induced pneumonitis. Physicians seeing such patients should
      be aware of this rare but real pulmonary toxicity. A delay in diagnosis and
      treatment can lead to potentially fatal outcomes.

PMID- 22993377
TI  - Modified docetaxel-cisplatin in combination with capecitabine as first-line
      treatment in metastatic gastric cancer. a phase II study.
AB  - The combination of docetaxel, cisplatin and fluorouracil is considered to be one
      of the reference regimens for advanced gastric cancer, but due to its major
      myelotoxicity, its use in clinical practice has become limited. This prospective
      phase II study evaluated the activity and toxicity of a modified regimen with
      lower doses of docetaxel and cisplatin combined with oral capecitabine instead of
      fluorouracil for patients with advanced gastric cancer. Treatment consisted of
      docetaxel at 60 mg/m(2) i.v. followed by cisplatin at 60 mg/m(2), both
      administered on day one, every three weeks. Capecitabine at 2 g/m(2) per day was
      administered in two divided doses for 14 days (days 2-15). Thirty six patients
      were enrolled in the study. The median age was 64 years and performance status
      (ECOG) was 0-1. All patients had advanced disease, 78% with liver metastases,
      100% with intra-abdominal lymph node metastases and 67% with peritoneal implants.
      Out of the 36 patients, 13 had undergone gastric resection, 13 had received
      adjuvant chemotherapy with irinotecan-leucovorin-fluorouracil, while seven
      patients had undergone adjuvant radiotherapy. The remaining 23 patients presented
      with advanced inoperable disease. Among 36 evaluable for response cases, there
      were 16 (44.4%) (Confidence Internal (CI) 95%=28-60%), partial responses. Stable
      disease was recorded in 12 (33.3%), resulting in an overall disease control rate
      of 78% (CI 95%=69-87%), while 8 (22.3%) patients progressed on chemotherapy. The
      median response duration was 6 (range=3-8) months. The median time-to-progression
      was 5 (range=3-6) months and the median survival (after the administration of a
      second-line chemotherapy in 12 patients), was 12 (range=5-24) months.
      Myelotoxocity was the main toxicity, with grade 3-4 neutropenia occurring in 18
      (50%) and febrile neutropenia in six (16%) patients. Granulocyte-Colony
      Stimulating Factor (G-CSF) support was given to 16 (44.4%) patients, while grade
      3 thrombocytopenia was recorded in two (6%). In conclusion, this modified regimen
      of docetaxel-cisplatin-capecitabine appears to have comparable efficacy with that
      reported for the reference regimen, with acceptable toxicity when G-CSF support
      is provided. However, because due to the small size of the study, further
      investigation is warranted.

PMID- 22993378
TI  - Long-term results of a phase II study of S-1 plus irinotecan in metastatic
      colorectal cancer.
AB  - AIM: The current study aimed to assess the long-term efficacy of combination
      therapy with oral S-1, a fluoropyrimidine prodrug, plus irinotecan in previously
      untreated patients with metastatic colorectal cancer. PATIENTS AND METHODS:
      Between April 2004 and February 2005, 41 patients with previously untreated
      advanced or recurrent colorectal cancer were enrolled in the study. Chemotherapy
      consisted of oral administration in S-1 at 40 mg/m(2) twice daily on days 1 to 14
      and intravenous infusion of irinotecan at 150 mg/m(2) on day 1 in a 21-day cycle.
      RESULTS: The median patient follow-up was 78.0 months. The median survival time
      was 23.7 months, and the 2-year survival rate was 50%. The median time to tumor
      progression was 8.3 months. CONCLUSION: The results of this long-term update
      confirmed that first-line combination therapy with oral S-1 plus irinotecan was
      effective in patients with metastatic colorectal cancer.

PMID- 22993379
TI  - Use of pretreatment metabolic tumor volumes on PET-CT to predict the survival of
      patients with squamous cell carcinoma of esophagus treated by curative surgery.
AB  - AIM: To investigate the prognostic role of the pretreatment metabolic tumor
      volume (MTV) as determined by Positron emission tomography--computed tomography
      (PET-CT) in patients with esophageal cancer undergoing curative surgery. PATIENTS
      AND METHODS: We retrospectively reviewed the data of 26 patients with squamous
      cell carcinoma of the esophagus, who underwent 18F-Fluorodeoxyglucose PET-CT
      before surgery. MTVs were defined as the volumes with FDG uptake above a
      standardized uptake value (SUV) of 2.5 (MTV2.5), or a fixed threshold of 20%
      (MTV20%) of the maximum intratumoral activity. Overall survival (OS) and disease
      free survival (DFS) were examined by the Kaplan-Meier method and the log-rank
      test. RESULTS: In a median follow-up of 15 months, 13 patients had died. The mean
      MTV2.5 was 18.9 +/- 15.4 ml (median, 16.0), whereas the mean MTV20% was 21.7 +/-
      15.0 ml (median, 19.1). Patients who had tumors of an MTV2.5 >16.0 ml had an
      inferior one-year OS compared with patients with a lower MTV2.5 (70% vs. 84%,
      p=0.018). Similarly, patients with an MTV20% >19.1 ml had poorer outcomes
      compared with patients who had small tumors, with one-year OS of 69% and 85%,
      respectively (p=0.016). No statistical significance was found in DFS for both MTV
      approaches. The SUVp-max had no impact on the OS and the DFS when using a median
      value of 8.3. CONCLUSION: Pretreatment MTV is a novel marker for OS of patients
      with esophageal cancer treated with curative surgery. For those with higher MTVs,
      more aggressive adjuvant treatments should be considered.

PMID- 22993381
TI  - Leptin and the placental response to maternal food restriction during early
      pregnancy in mice.
AB  - Several studies have demonstrated that maternal undernutrition or overnutrition
      during pregnancy can have negative consequences for the health of children born
      to these pregnancies, but the physiological mechanisms by which this occurs are
      not completely understood. During periods of food restriction, concentrations of
      leptin decline, whereas leptin is elevated in obesity, suggesting that it may
      play a role in the response to altered nutrition during pregnancy. This study
      compares placental development and global placental gene expression profiles at
      Day 11.5 in pregnant control mice, mice that were undernourished, and mice that
      were undernourished but given leptin. Placentas from mothers exposed to food
      restriction preserved the placental labyrinth zone at the expense of the
      junctional zone, an effect abrogated in the restricted plus leptin group, which
      had a significant decrease in the labyrinth zone area compared with controls.
      Similarly, there were more significant differences in gene expression between
      placentas from control and restricted plus leptin mothers (1128 differentially
      expressed genes) than between placentas of control and restricted mothers (281
      differentially expressed genes). We conclude that the presence of high
      concentrations of circulating leptin during food restriction disrupts the normal
      adaptive response of the placenta to reduced energy availability.

PMID- 22993383
TI  - Sensitivity and specificity of mammographic screening as practised in Vermont and
      Norway.
AB  - OBJECTIVE: The aim of this study was to examine the sensitivity and specificity
      of screening mammography as performed in Vermont, USA, and Norway. METHODS:
      Incident screening data from 1997 to 2003 for female patients aged 50-69 years
      from the Vermont Breast Cancer Surveillance System (116 996 subsequent screening
      examinations) and the Norwegian Breast Cancer Screening Program (360 872
      subsequent screening examinations) were compared. Sensitivity and specificity
      estimates for the initial (based on screening mammogram only) and final
      (screening mammogram plus any further diagnostic imaging) interpretations were
      directly adjusted for age using 5-year age intervals for the combined Vermont and
      Norway population, and computed for 1 and 2 years of follow-up, which ended at
      the time of the next screening mammogram. RESULTS: For the 1-year follow-up,
      sensitivities for initial assessments were 82.0%, 88.2% and 92.5% for 1-, 2- and
      >2-year screening intervals, respectively, in Vermont (p=0.022). For final
      assessments, the values were 73.6%, 83.3% and 81.2% (p=0.047), respectively. For
      Norway, sensitivities for initial assessments were 91.0% and 91.3% (p=0.529) for
      2- and >2-year intervals, and 90.7% and 91.3%, respectively, for final
      assessments (p=0.630). Specificity was lower in Vermont than in Norway for each
      screening interval and for all screening intervals combined, for both initial
      (90.6% vs 97.8% for all intervals; p<0.001) and final (98.8% vs 99.5% for all
      intervals; p<0.001) assessments. CONCLUSION: Our study showed higher sensitivity
      and specificity in a biennial screening programme with an independent double
      reading than in a predominantly annual screening program with a single reading.
      ADVANCES IN KNOWLEDGE: This study demonstrates that higher recall rates and lower
      specificity are not always associated with higher sensitivity of screening
      mammography. Differences in the screening processes in Norway and Vermont suggest
      potential areas for improvement in the latter.

PMID- 22993384
TI  - High-resolution CT findings of pulmonary infections after orthotopic liver
      transplantation in 453 patients.
AB  - OBJECTIVES: The objective of this study was to review the high-resolution CT
      (HRCT) findings in patients with pulmonary infection after orthotopic liver
      transplantation (OLT) and to determine distinguishing findings among the various
      types of infection. METHODS: This study included 453 consecutive liver transplant
      recipients with pulmonary infection, on whom HRCT of the chest was performed
      within 24 h of the beginning of symptoms and for whom proven diagnosis had taken
      place within 1 week of the onset of symptoms. Two radiologists analysed the CT
      images; final decisions regarding the findings were reached by consensus.
      RESULTS: Bacterial and viral pneumonia made up the bulk of infections (63.4% and
      29.4%, respectively), followed by fungal infiltrates (24.5%). Large nodules were
      most common in patients with fungal pneumonia, having been seen in 38 (54%) of
      the 70 patients with fungal pneumonia, 22 (10%) of 220 with bacterial pneumonia
      (p=0.0059) and 6 (8%) of 78 with viral pneumonia (p=0.0011). The halo sign was
      also more frequent in patients with fungal pneumonia, having been seen in 38
      (54%) of the 70 patients with fungal pneumonia, 17 (8%) of 220 with bacterial
      pneumonia (p=0.0026) and 7 (9%) of 78 with viral pneumonia (p=0.0015). There was
      no statistically significant difference in the prevalence of the other HRCT
      patterns including air-space consolidation, ground-glass attenuation and small
      nodules among bacterial, viral and fungal infections (all p>0.05). CONCLUSION:
      The presence of large nodules with the halo sign is most suggestive of fungal
      infection after OLT. Other HRCT patterns are not helpful in distinguishing among
      the various types of infection seen in liver transplant recipients.

PMID- 22993382
TI  - The reproductive phenotype of mice null for transcription factor Kruppel-like
      factor 13 suggests compensatory function of family member Kruppel-like factor 9
      in the peri-implantation uterus.
AB  - The ovarian hormones estrogen and progesterone promote uterine receptivity and
      successful pregnancy through their cognate receptors functioning in concert with
      context-dependent nuclear coregulators. Previously, we showed that the
      transcription factor Kruppel-like factor (KLF) 9 is a progesterone receptor (PGR)
      coactivator in the uterus and that mice null for Klf9 exhibit subfertility and
      reduced progesterone sensitivity. The highly related family member KLF13 displays
      increased expression in uteri of pregnant and nonpregnant Klf9 null mice and
      similarly regulates PGR-mediated transactivation in endometrial stromal cells.
      However, a uterine phenotype with loss of Klf13 has not been reported. In the
      present study, we demonstrate that Klf13 deficiency in mice did not compromise
      female fertility and pregnancy outcome. Klf13 null females had litter sizes,
      numbers of implanting embryos, uterine morphology, and ovarian steroid hormone
      production comparable to those of wild-type (WT) counterparts. Further, pregnant
      WT and Klf13 null females at Day Postcoitum (DPC) 3.5 had similar uterine Pgr,
      estrogen receptor, and Wnt-signaling component transcript levels. Nuclear levels
      of KLF9 were higher in Klf13 null than in WT uteri at DPC 3.5, albeit whole
      tissue KLF9 protein and transcript levels did not differ between genotypes. The
      lack of a similar induction of nuclear KLF9 levels in uteri of virgin Klf13((-/
      )) mice relative to WT uteri was associated with lower stromal PGR expression. In
      differentiating human endometrial stromal cells, coincident KLF9/KLF13 knockdown
      by small interfering RNA targeting reduced decidualization-associated PRL
      expression, whereas KLF9 and KLF13 knockdowns alone reduced transcript levels of
      WNT4 and BMP2, respectively. Results suggest that KLF9 and KLF13 functionally
      compensate in peri-implantation uterus for pregnancy success.

PMID- 22993385
TI  - Inter- and intraradiologist variability in the BI-RADS assessment and breast
      density categories for screening mammograms.
AB  - OBJECTIVE: The aim of this study was to evaluate reader variability in screening
      mammograms according to the American College of Radiology Breast Imaging
      Reporting and Data System (BI-RADS) assessment and breast density categories.
      METHODS: A stratified random sample of 100 mammograms was selected from a
      population-based breast cancer screening programme in Barcelona, Spain: 13
      histopathologically confirmed breast cancers and 51 with true-negative and 36
      with false-positive results. 21 expert radiologists from radiological units of
      breast cancer screening programmes in Catalonia, Spain, reviewed the mammography
      images twice within a 6-month interval. The readers described each mammography
      using BI-RADS assessment and breast density categories. Inter- and
      intraradiologist agreement was assessed using percentage of concordance and the
      kappa (kappa) statistic. RESULTS: Fair interobserver agreement was observed for
      the BI-RADS assessment [kappa=0.37, 95% confidence interval (CI) 0.36-0.38]. When
      the categories were collapsed in terms of whether additional evaluation was
      required (Categories III, 0, IV, V) or not (I and II), moderate agreement was
      found (kappa=0.53, 95% CI 0.52-0.54). Intra-observer agreement for BI-RADS
      assessment was moderate using all categories (kappa=0.53, 95% CI 0.50-0.55) and
      substantial on recall (kappa=0.66, 95% CI 0.63-0.70). Regarding breast density,
      inter- and intraradiologist agreement was substantial (kappa=0.73, 95% CI 0.72
      0.74 and kappa=0.69, 95% CI 0.68-0.70, respectively). CONCLUSION: We observed a
      substantial intra-observer agreement in the BI-RADS assessment but only moderate
      interobserver agreement. Both inter- and intra-observer agreement in mammographic
      interpretation of breast density was substantial. Advances in knowledge
      Educational efforts should be made to decrease radiologists' variability in BI
      RADS assessment interpretation in population-based breast screening programmes.

PMID- 22993386
TI  - Incidence of symptomatic brain metastasis following radical radiotherapy for non
      small cell lung cancer: is there a role for prophylactic cranial irradiation?
AB  - OBJECTIVE: Brain metastases following radical radiotherapy for non-small cell
      lung cancer (NSCLC) are a recognised phenomenon; however, the incidence of
      symptomatic brain metastasis is currently unknown. The aim of the study was to
      identify the number of patients, staged in accordance with National Institute for
      Health and Clinical Excellence (NICE) guidance, who developed symptomatic brain
      metastasis following radical radiotherapy. There are two aims: to evaluate NICE
      guidance; and to provide vital information on the likely benefit of prophylactic
      cranial irradiation (PCI) in reducing neurological symptoms from brain
      metastasis. METHODS: A retrospective review of 455 patients with NSCLC who had
      undergone radical radiotherapy in 2009 and 2010 was performed. Computer-based
      systems were used to identify patient and tumour demographics, the staging
      procedures performed and whether brain imaging had identified brain metastasis in
      the follow-up period. RESULTS: The total number of patients with brain metastasis
      within 6 months was 3.7%. The proportion of brain metastasis within 6 months in
      Stage I, II and III NSCLC throughout both years was 2.8%, 1.0% and 5.7%,
      respectively. Within the follow-up period (median 16 months, range 6-30 months),
      the total number of patients who developed symptomatic brain metastasis was 7.9%.
      CONCLUSION: Patients staged in accordance with NICE guidance, of whom only 7.7%
      underwent brain staging, have a minimal incidence of brain metastasis following
      radical radiotherapy. The number of patients developing symptoms from brain
      metastasis following radical radiotherapy may be less than the morbidity caused
      by PCI. ADVANCES IN KNOWLEDGE: This finding supports the NICE guidance and brings
      into question the potential benefit of PCI.

PMID- 22993388
TI  - Use of 111-Indium-labeled autologous eosinophils to establish the in vivo
      kinetics of human eosinophils in healthy subjects.
AB  - Eosinophils are the major cellular effectors of allergic inflammation and
      represent an important therapeutic target. Although the genesis and activation of
      eosinophils have been extensively explored, little is known about their
      intravascular kinetics or physiological fate. This study was designed to
      determine the intravascular life span of eosinophils, their partitioning between
      circulating and marginated pools, and sites of disposal in healthy persons. Using
      autologous, minimally manipulated 111-Indium-labeled leukocytes with blood
      sampling, we measured the eosinophil intravascular residence time as 25.2 hours
      (compared with 10.3 hours for neutrophils) and demonstrated a substantial
      marginated eosinophil pool. gamma camera imaging studies using purified
      eosinophils demonstrated initial retention in the lungs, with early
      redistribution to the liver and spleen, and evidence of recirculation from a
      hepatic pool. This work provides the first in vivo measurements of eosinophil
      kinetics in healthy volunteers and shows that 111-Indium-labeled eosinophils can
      be used to monitor the fate of eosinophils noninvasively.

PMID- 22993389
TI  - Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate
      dehydrogenase-deficient children receiving dapsone.
AB  - Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency.
      However, most clinical data are from isolated case reports. In 2 clinical trials
      of antimalarial preparations containing dapsone (4,4'-diaminodiphenylsulfone; 2.5
      mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD
      deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency
      received this agent. In the first 2 groups, there was a maximum decrease in
      hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was
      significantly greater than for the comparator group receiving artemether
      lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, 
      1.15). Hemoglobin concentrations were decreased by >= 40% versus pretreatment in
      24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood
      transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin
      was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood
      transfusion. All children eventually recovered. All the G6PD-deficient children
      had the G6PD A- variant, ie, mutations V68M and N126D. Drug-induced acute
      hemolytic anemia in G6PD A- subjects can be life-threatening, depending on the
      nature and dosage of the drug trigger. Therefore, contrary to current perception,
      in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This
      study is registered at http://www.clinicaltrials.gov as NCT00344006 and
      NCT00371735.

PMID- 22993390
TI  - Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation
      leading to high-level PD-1 expression on CD8 T cells.
AB  - Lymphatic endothelial cells (LECs) induce peripheral tolerance by direct
      presentation to CD8 T cells (T(CD8)). We demonstrate that LECs mediate deletion
      only via programmed cell death-1 (PD-1) ligand 1, despite expressing ligands for
      the CD160, B- and T-lymphocyte attenuator, and lymphocyte activation gene-3
      inhibitory pathways. LECs induce activation and proliferation of T(CD8), but lack
      of costimulation through 4-1BB leads to rapid high-level expression of PD-1,
      which in turn inhibits up-regulation of the high-affinity IL-2 receptor that is
      necessary for T(CD8) survival. Rescue of tyrosinase-specific T(CD8) by
      interference with PD-1 or provision of costimulation results in autoimmune
      vitiligo, demonstrating that LECs are significant, albeit suboptimal, antigen
      presenting cells. Because LECs express numerous peripheral tissue antigens, lack
      of costimulation coupled to rapid high-level up-regulation of inhibitory
      receptors may be generally important in systemic peripheral tolerance.

PMID- 22993392
TI  - Prevention and management of neutropenic sepsis in patients with cancer: summary
      of NICE guidance.

PMID- 22993391
TI  - In vivo roles of factor XII.
AB  - Coagulation factor XII (FXII, Hageman factor, EC = 3.4.21.38) is the zymogen of
      the serine protease, factor XIIa (FXIIa). FXII is converted to FXIIa through
      autoactivation induced by "contact" to charged surfaces. FXIIa is of crucial
      importance for fibrin formation in vitro, but deficiency in the protease is not
      associated with excessive bleeding. For decades, FXII was considered to have no
      function for coagulation in vivo. Our laboratory developed the first murine
      knockout model of FXII. Consistent with their human counterparts, FXII(-/-) mice
      have a normal hemostatic capacity. However, thrombus formation in FXII(-/-) mice
      is largely defective, and the animals are protected from experimental cerebral
      ischemia and pulmonary embolism. This murine model has created new interest in
      FXII because it raises the possibility for safe anticoagulation, which targets
      thrombosis without influence on hemostasis. We recently have identified platelet
      polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII
      activators with implications on the initiation of thrombosis and edema during
      hypersensitivity reactions. Independent of its protease activity, FXII exerts
      mitogenic activity with implications for angiogenesis. The goal of this review is
      to summarize the in vivo functions of FXII, with special focus to its functions
      in thrombosis and vascular biology.

PMID- 22993394
TI  - House call.

PMID- 22993393
TI  - Diagnosis and management of headaches in young people and adults: summary of NICE
      guidance.

PMID- 22993395
TI  - Can Jeremy Hunt please explain?

PMID- 22993397
TI  - American countries face major health problems because of aging and obesity,
      report says.

PMID- 22993398
TI  - GMC refers investigator in libel case to fitness to practise panel.

PMID- 22993399
TI  - Europe's plan to tighten regulation of devices will not reach US standards.

PMID- 22993400
TI  - Woman is sentenced to eight years in prison for procuring miscarriage.

PMID- 22993401
TI  - Researchers find no link between XMRV and chronic fatigue syndrome.

PMID- 22993402
TI  - Faster reconfiguration of NHS services is needed for next two years says NHS
      chief.

PMID- 22993403
TI  - Dual roles of PARP-1 promote cancer growth and progression.
AB  - PARP-1 is an abundant nuclear enzyme that modifies substrates by poly(ADP-ribose)
      ylation. PARP-1 has well-described functions in DNA damage repair and also
      functions as a context-specific regulator of transcription factors. With multiple
      models, data show that PARP-1 elicits protumorigenic effects in androgen receptor
      (AR)-positive prostate cancer cells, in both the presence and absence of
      genotoxic insult. Mechanistically, PARP-1 is recruited to sites of AR function,
      therein promoting AR occupancy and AR function. It was further confirmed in
      genetically defined systems that PARP-1 supports AR transcriptional function, and
      that in models of advanced prostate cancer, PARP-1 enzymatic activity is
      enhanced, further linking PARP-1 to AR activity and disease progression. In vivo
      analyses show that PARP-1 activity is required for AR function in xenograft
      tumors, as well as tumor cell growth in vivo and generation and maintenance of
      castration resistance. Finally, in a novel explant system of primary human
      tumors, targeting PARP-1 potently suppresses tumor cell proliferation.
      Collectively, these studies identify novel functions of PARP-1 in promoting
      disease progression, and ultimately suggest that the dual functions of PARP-1 can
      be targeted in human prostate cancer to suppress tumor growth and progression to
      castration resistance. SIGNIFICANCE: These studies introduce a paradigm shift
      with regard to PARP-1 function in human malignancy, and suggest that the dual
      functions of PARP-1 in DNA damage repair and transcription factor regulation can
      be leveraged to suppress pathways critical for promalignant phenotypes in
      prostate cancer cells by modulation of the DNA damage response and hormone
      signaling pathways. The combined studies highlight the importance of dual PARP-1
      function in malignancy and provide the basis for therapeutic targeting.

PMID- 22993405
TI  - Aryl hydrocarbon receptor-induced adrenomedullin mediates cigarette smoke
      carcinogenicity in humans and mice.
AB  - Cigarette smoking (CS) is a leading cause of death worldwide. The aryl
      hydrocarbon receptor (AHR) is partially responsible for tobacco-induced
      carcinogenesis although the underlying mechanisms involving early effector genes
      have yet to be determined. Here, we report that adrenomedullin (ADM)
      significantly contributes to the carcinogenicity of tobacco-activated AHR. CS and
      AHR activating ligands induced ADM in vitro and in vivo but not in AHR-deficient
      fibroblasts and mice. Ectopic transfection of AHR rescued ADM expression in AHR(
      /-) fibroblasts whereas AHR blockage with siRNA in wild type cells significantly
      decreased ADM expression. AHR regulates ADM expression through two intronic
      xenobiotic response elements located close to the start codon in the ADM gene.
      Using tissue microarrays we showed that ADM and AHR were coupregulated in lung
      tumor biopsies from smoker patients. Microarray meta-analysis of 304 independent
      microarray experiments showed that ADM is elevated in smokers and smokers with
      cancer. In addition, ADM coassociated with a subset of AHR responsive genes and
      efficiently differentiated patients with lung cancer from nonsmokers. In a novel
      preclinical model of CS-induced tumor progression, host exposure to CS extracts
      significantly elevated tumor ADM although systemic treatment with the ADM
      antagonist NSC16311 efficiently blocked tobacco-induced tumor growth. In
      conclusion, ADM significantly contributes the carcinogenic effect of AHR and
      tobacco combustion products. We suggest that therapeutics targeting the AHR/ADM
      axis may be of clinical relevance in the treatment of tobacco-induced pulmonary
      malignancies.

PMID- 22993404
TI  - Rat Mcs1b is concordant to the genome-wide association-identified breast cancer
      risk locus at human 5q11.2 and MIER3 is a candidate cancer susceptibility gene.
AB  - Low-penetrance alleles associated with breast cancer risk have been identified in
      population-based studies. Most risk loci contain either no or multiple potential
      candidate genes. Rat mammary carcinoma susceptibility 1b (Mcs1b) is a
      quantitative trait locus on RN02 that confers decreased susceptibility when
      Copenhagen (COP)-resistant alleles are introgressed into a Wistar Furth (WF)
      susceptible genome. Five WF.COP congenic lines containing COP RN02 segments were
      compared. One line developed an average of 3.4 +/- 2.0 and 5.5 +/- 3.6 mammary
      carcinomas per rat +/- SD when females were Mcs1b-resistant homozygous and Mcs1b
      heterozygous, respectively. These phenotypes were significantly different from
      susceptible genotype littermates (7.8 +/- 3.1 mean mammary carcinomas per rat +/-
      SD, P = 0.0001 and P = 0.0413, respectively). All other congenic lines tested
      were susceptible. Thus, Mcs1b was narrowed to 1.8 Mb of RN02 between genetic
      markers ENSRNOSNP2740854 and g2UL2-27. Mammary gland-graft carcinoma
      susceptibility assays were used to determine that donor (P = 0.0019), but not
      recipient Mcs1b genotype (P = 0.9381), was associated with ectopic mammary
      carcinoma outcome. Rat Mcs1b contains sequence orthologous to human 5q11.2, a
      breast cancer susceptibility locus identified in multiple genome-wide association
      studies. Human/rat MAP3K1/Map3k1 and mesoderm induction early response (MIER;
      MIER3)/MIER3 are within these orthologous segments. We identified MIER3 as a
      candidate Mcs1b gene based on 4.5-fold higher mammary gland levels of MIER3
      transcripts in susceptible compared with Mcs1b-resistant females. These data
      suggest that the human 5q11.2 breast cancer risk allele marked by rs889312 is
      mammary gland autonomous, and MIER3 is a candidate breast cancer susceptibility
      gene.

PMID- 22993406
TI  - Evaluation of the new Elecsys Toxo IgG avidity assay for toxoplasmosis and new
      insights into the interpretation of avidity results.
AB  - Detection and treatment of acute toxoplasmosis during pregnancy can avoid severe
      disease of the fetus. In this context, assessment of anti-Toxoplasma IgG avidity
      has been shown to exclude recent infection. The Elecsys Toxo IgG and IgM assays
      (Roche Diagnostics) have been validated for screening pregnant women and a new
      assay, Elecsys Toxo IgG Avidity, was recently developed. Our aims were to
      investigate the performance characteristics of this new avidity assay and explore
      whether additional information can be provided by avidity assays. The Elecsys
      assay was compared with the Vidas (bioMerieux) and Architect (Abbott) Avidity
      assays using two sets of serum samples (n = 291 and n = 255). The rate of general
      agreement between the Elecsys and Vidas assays was 74%, and that between the
      Elecsys and Architect assays was 83%. For 11% of the serum samples, avidity was
      high with the Vidas assay and within the gray zone with the Elecsys assay. None
      of the assays detected high-avidity antibodies in serum taken <4 months after
      infection. Avidity values of >90% were exclusively reported in sera taken >9
      months after infection by the Elecsys and Architect assays. Almost all avidities
      of <19% with the Elecsys assay and <17% with the Architect assay corresponded to
      sera taken <3 and <2 months after infection, respectively. The Elecsys IgG
      Avidity assay can be used to exclude recent infection. New ways of interpreting
      the avidity result are also suggested: very high or low values could exclude
      infections within the last 9 months or help to confirm a recent infection,
      respectively. However, these potential interpretations require further
      investigation.

PMID- 22993407
TI  - Evaluation of immunostimulatory activities of synthetic mannose-containing
      structures mimicking the beta-(1->2)-linked cell wall mannans of Candida
      albicans.
AB  - Immunostimulatory properties of synthetic structures mimicking the beta-(1->2)
      linked mannans of Candida albicans were evaluated in vitro. Contrary to earlier
      observations, tumor necrosis factor (TNF) production was not detected after
      stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4
      bis(alpha-D-mannopyranosyloxy)butane induced TNF and some molecules induced low
      levels of gamma interferon (IFN-gamma) in human peripheral blood mononuclear
      cells (PBMC).

PMID- 22993408
TI  - Development of monoclonal antibodies to West Nile virus and their application in
      immunohistochemistry.
AB  - West Nile virus (WNV) is endemic throughout Africa, Eurasia, America, and
      Australia and has important implications for avian, horse, and human health. In
      these regions, dead birds are monitored for the presence of WNV through
      immunohistochemistry (IHC) and PCR. However, a number of the tools for IHC are
      inadequate owing to their cross-reactivity to other Japanese encephalitis
      serogroup viruses. Here we have established eight monoclonal antibodies (MAbs) to
      WNV. Four of them bound to the envelope protein, three of them bound to
      nonstructural protein 1 (NS1), and one bound to precursor membrane protein (prM),
      as shown by Western blot analysis. The anti-NS1 MAbs and the anti-prM MAb did not
      cross-react with Japanese encephalitis virus (JEV), Murray valley encephalitis
      virus, or St. Louis encephalitis virus in an indirect enzyme-linked immunosorbent
      assay. One NS1-specific MAb, SHW-32B1, and the previously reported NS1-specific
      MAb, SHW-7A11, were shown by IHC to specifically detect the cytoplasm of
      degenerated cells in the heart and brain of a WNV-infected goose. Neither of
      these MAbs were shown by IHC to cross-react with degenerated cells in the brain
      of a JEV-infected pig. These MAbs are the first reported anti-NS1 MAbs that can
      be used for WNV-specific IHC using formalin-fixed, paraffin-embedded sections.
      They may be useful for WNV research and surveillance.

PMID- 22993409
TI  - Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea
      using a composite reference standard.
AB  - Typhoid fever remains a major global health problem. A major impediment to
      improving outcomes is the lack of appropriate diagnostic tools, which have not
      significantly improved in low-income settings for 100 years. We evaluated two
      commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype
      (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously
      reported high-burden area of Papua New Guinea. Samples were collected from 530
      outpatients with axillary temperatures of >=37.5 degrees C, and analysis was
      conducted on all malaria-negative samples (n = 500). A composite reference
      standard of blood culture and PCR was used, by which 47 participants (9.4%) were
      considered typhoid fever positive. The sensitivity and specificity of the Tubex
      (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively)
      tests were not high enough to warrant their ongoing use in this setting; however,
      the sensitivity and specificity for the TR-02 prototype were promising (89.4% and
      85.0%, respectively). An axillary temperature of >=38.5 degrees C correlated with
      typhoid fever (P = 0.014). With an appropriate diagnostic test, conducting
      typhoid fever diagnosis only on patients with high-grade fever could dramatically
      decrease the costs associated with diagnosis while having no detrimental impact
      on the ability to accurately diagnose the illness.

PMID- 22993410
TI  - Comparison of immune responses to the O-specific polysaccharide and
      lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi adult patients with
      cholera.
AB  - Immunity against Vibrio cholerae O1 is serogroup specific, and serogrouping is
      defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS).
      Despite this, human immune responses to V. cholerae OSP have not previously been
      characterized. We assessed immune responses against V. cholerae OSP in adults
      with cholera caused by V. cholerae O1 El Tor serotype Inaba or Ogawa in Dhaka,
      Bangladesh, using O1 OSP-core-bovine serum albumin (OSPc:BSA) conjugates;
      responses targeted OSP in these conjugates. Responses of Inaba-infected patients
      to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from
      the acute to convalescent phases of illness, and the responses correlated well
      between OSP and LPS (R = 0.86, 0.73, and 0.91, respectively; P < 0.01). Plasma
      IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also
      correlated well with each other (R = 0.60, 0.60, and 0.92, respectively; P <
      0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the
      respective serogroup-specific vibriocidal antibodies (R = 0.80 and 0.66,
      respectively; P < 0.001). Addition of either OSPc:BSA or LPS, but not BSA, to
      vibriocidal assays inhibited vibriocidal responses in a comparable and
      concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were
      also similar. Our study is the first to characterize anti-OSP immune responses in
      patients with cholera and suggests that responses targeting V. cholerae LPS,
      including vibriocidal responses that correlate with protection against cholera,
      predominantly target OSP. Induction of anti-OSP responses may be associated with
      protection against cholera, and our results may support the development of a
      vaccine targeting V. cholerae OSP.

PMID- 22993411
TI  - Profiling the native specific human humoral immune response to Sudan Ebola virus
      strain Gulu by chemiluminescence enzyme-linked immunosorbent assay.
AB  - Ebolavirus, a member of the family Filoviridae, causes high lethality in humans
      and nonhuman primates. Research focused on protection and therapy for Ebola virus
      infection has investigated the potential role of antibodies. Recent evidence
      suggests that antibodies can be effective in protection from lethal challenge
      with Ebola virus in nonhuman primates. However, despite these encouraging
      results, studies have not yet determined the optimal antibodies and composition
      of an antibody cocktail, if required, which might serve as a highly effective and
      efficient prophylactic. To better understand optimal antibodies and their
      targets, which might be important for protection from Ebola virus infection, we
      sought to determine the profile of viral protein-specific antibodies generated
      during a natural cycle of infection in humans. To this end, we characterized the
      profile of antibodies against individual viral proteins of Sudan Ebola virus
      (Gulu) in human survivors and nonsurvivors of the outbreak in Gulu, Uganda, in
      2000-2001. We developed a unique chemiluminescence enzyme-linked immunosorbent
      assay (ELISA) for this purpose based on the full-length recombinant viral
      proteins NP, VP30, and VP40 and two recombinant forms of the viral glycoprotein
      (GP(1-294) and GP(1-649)) of Sudan Ebola virus (Gulu). Screening results revealed
      that the greatest immunoreactivity was directed to the viral proteins NP and GP(1
      649), followed by VP40. Comparison of positive immunoreactivity between the viral
      proteins NP, GP(1-649), and VP40 demonstrated a high correlation of
      immunoreactivity between these viral proteins, which is also linked with
      survival. Overall, our studies of the profile of immunorecognition of antibodies
      against four viral proteins of Sudan Ebola virus in human survivors may
      facilitate development of effective monoclonal antibody cocktails in the future.

PMID- 22993412
TI  - Insights from natural infection-derived immunity to cholera instruct vaccine
      efforts.

PMID- 22993413
TI  - Unrestrained p38 MAPK activation in Dusp1/4 double-null mice induces
      cardiomyopathy.
AB  - RATIONALE: Mitogen-activated protein kinases (MAPKs) are activated in the heart
      by disease-inducing and stress-inducing stimuli, where they participate in
      hypertrophy, remodeling, contractility, and heart failure. A family of dual
      specificity phosphatases (DUSPs) directly inactivates each of the MAPK terminal
      effectors, potentially serving a cardioprotective role. OBJECTIVE: To determine
      the role of DUSP1 and DUSP4 in regulating p38 MAPK function in the heart and the
      effect on disease. METHODS AND RESULTS: Here, we generated mice and mouse
      embryonic fibroblasts lacking both Dusp1 and Dusp4 genes. Although single nulls
      showed no molecular effects, combined disruption of Dusp1/4 promoted unrestrained
      p38 MAPK activity in both mouse embryonic fibroblasts and the heart, with no
      change in the phosphorylation of c-Jun N-terminal kinases or extracellular signal
      regulated kinases at baseline or with stress stimulation. Single disruption of
      either Dusp1 or Dusp4 did not result in cardiac pathology, although Dusp1/4
      double-null mice exhibited cardiomyopathy and increased mortality with aging.
      Pharmacological inhibition of p38 MAPK with SB731445 ameliorated cardiomyopathy
      in Dusp1/4 double-null mice, indicating that DUSP1/4 function primarily through
      p38 MAPK in affecting disease. At the cellular level, unrestrained p38 MAPK
      activity diminished cardiac contractility and Ca2+ handling, which was acutely
      reversed with a p38 inhibitory compound. Poor function in Dusp1/4 double-null
      mice also was partially rescued by phospholamban deletion. CONCLUSIONS: Our data
      demonstrate that Dusp1 and Dusp4 are cardioprotective genes that play a critical
      role in the heart by dampening p38 MAPK signaling that would otherwise reduce
      contractility and induce cardiomyopathy.

PMID- 22993414
TI  - An objective measure of stimulus-evoked pain.

PMID- 22993415
TI  - Decoding the contents of visual short-term memory from human visual and parietal
      cortex.
AB  - How content is stored in the human brain during visual short-term memory (VSTM)
      is still an open question. Different theories postulate storage of remembered
      stimuli in prefrontal, parietal, or visual areas. Aiming at a distinction between
      these theories, we investigated the content-specificity of BOLD signals from
      various brain regions during a VSTM task using multivariate pattern
      classification. To participate in memory maintenance, candidate regions would
      need to have information about the different contents held in memory. We
      identified two brain regions where local patterns of fMRI signals represented the
      remembered content. Apart from the previously established storage in visual
      areas, we also discovered an area in the posterior parietal cortex where activity
      patterns allowed us to decode the specific stimuli held in memory. Our results
      demonstrate that storage in VSTM extends beyond visual areas, but no frontal
      regions were found. Thus, while frontal and parietal areas typically coactivate
      during VSTM, maintenance of content in the frontoparietal network might be
      limited to parietal cortex.

PMID- 22993417
TI  - Disruption of dentate gyrus blocks effect of visual input on spatial firing of
      CA1 neurons.
AB  - The role of dentate gyrus in hippocampal mnemonic processing is uncertain. One
      proposed role of dentate gyrus is binding internally generated spatial
      representation with sensory information on external landmarks. To test this
      hypothesis, we compared effects of visual input on spatial firing of CA1 neurons
      in Bax knock-out mice in which dentate gyrus neural circuitry is selectively
      disrupted. Whereas spatial selectivity of CA1 neuronal firing was significantly
      higher under normal illumination than complete darkness in wild-type mice, it was
      similarly low in both illumination conditions in Bax knock-out mice. Also,
      whereas the spatial location of neuronal firing was more stably maintained in the
      light than in the dark condition in wild-type mice, it was similarly unstable in
      both illumination conditions in Bax knock-out mice. These results show that
      visual input allows selective and stable spatial firing of CA1 neurons in normal
      animals, but this effect is lost if dentate gyrus neural circuitry is disrupted.
      Our results provide empirical support for the proposed role of dentate gyrus in
      aligning internally generated spatial representation to external landmarks in
      building a unified representation of external space.

PMID- 22993416
TI  - The relationship between working memory storage and elevated activity as measured
      with functional magnetic resonance imaging.
AB  - Does the sustained, elevated neural activity observed during working memory tasks
      reflect the short-term retention of information? Functional magnetic resonance
      imaging (fMRI) data of delayed recognition of visual motion in human participants
      were analyzed with two methods: a general linear model (GLM) and multivoxel
      pattern analysis. Although the GLM identified sustained, elevated delay-period
      activity in superior and lateral frontal cortex and in intraparietal sulcus,
      pattern classifiers were unable to recover trial-specific stimulus information
      from these delay-active regions. The converse-no sustained, elevated delay-period
      activity but successful classification of trial-specific stimulus information-was
      true of posterior visual regions, including area MT+ (which contains both middle
      temporal area and medial superior temporal area) and calcarine and pericalcarine
      cortex. In contrast to stimulus information, pattern classifiers were able to
      extract trial-specific task instruction-related information from frontal and
      parietal areas showing elevated delay-period activity. Thus, the elevated delay
      period activity that is measured with fMRI may reflect processes other than the
      storage, per se, of trial-specific stimulus information. It may be that the short
      term storage of stimulus information is represented in patterns of
      (statistically) "subthreshold" activity distributed across regions of low-level
      sensory cortex that univariate methods cannot detect.

PMID- 22993419
TI  - Loss of retinoschisin (RS1) cell surface protein in maturing mouse rod
      photoreceptors elevates the luminance threshold for light-driven translocation of
      transducin but not arrestin.
AB  - Loss of retinoschisin (RS1) in Rs1 knock-out (Rs1-KO) retina produces a post
      photoreceptor phenotype similar to X-linked retinoschisis in young males.
      However, Rs1 is expressed strongly in photoreceptors, and Rs1-KO mice have early
      reduction in the electroretinogram a-wave. We examined light-activated transducin
      and arrestin translocation in young Rs1-KO mice as a marker for functional
      abnormalities in maturing rod photoreceptors. We found a progressive reduction in
      luminance threshold for transducin translocation in wild-type (WT) retinas
      between postnatal days P18 and P60. At P21, the threshold in Rs1-KO retinas was
      10-fold higher than WT, but it decreased to <2.5-fold higher by P60. Light
      activated arrestin translocation and re-translocation of transducin in the dark
      were not affected. Rs1-KO rod outer segment (ROS) length was significantly
      shorter than WT at P21 but was comparable with WT at P60. These findings
      suggested a delay in the structural and functional maturation of Rs1-KO ROS.
      Consistent with this, transcription factors CRX and NRL, which are fundamental to
      maturation of rod protein expression, were reduced in ROS of Rs1-KO mice at P21
      but not at P60. Expression of transducin was 15-30% lower in P21 Rs1-KO ROS and
      transducin GTPase hydrolysis was nearly twofold faster, reflecting a 1.7- to 2.5
      fold increase in RGS9 (regulator of G-protein signaling) level. Transduction
      protein expression and activity levels were similar to WT at P60. Transducin
      translocation threshold elevation indicates photoreceptor functional
      abnormalities in young Rs1-KO mice. Rapid reduction in threshold coupled with age
      related changes in transduction protein levels and transcription factor
      expression are consistent with delayed maturation of Rs1-KO photoreceptors.

PMID- 22993418
TI  - Adaptive regulation maintains posttetanic potentiation at cerebellar granule cell
      synapses in the absence of calcium-dependent PKC.
AB  - Posttetanic potentiation (PTP) is a transient, calcium-dependent increase in the
      efficacy of synaptic transmission following elevated presynaptic activity. The
      calcium-dependent protein kinase C (PKC(Ca)) isoforms PKCalpha and PKCbeta
      mediate PTP at the calyx of Held synapse, with PKCbeta contributing significantly
      more than PKCalpha. It is not known whether PKC(Ca) isoforms play a conserved
      role in PTP at other synapses. We examined this question at the parallel fiber ->
      Purkinje cell (PF->PC) synapse, where PKC inhibitors suppress PTP. We found that
      PTP is preserved when single PKC(Ca) isoforms are knocked out and in
      PKCalpha/beta double knock-out (dko) mice, even though in the latter all PKC(Ca)
      isoforms are eliminated from granule cells. However, in contrast to wild-type and
      single knock-out animals, PTP in PKCalpha/beta dko animals is not suppressed by
      PKC inhibitors. These results indicate that PKC(Ca) isoforms mediate PTP at the
      PF->PC synapse in wild-type and single knock-out animals. However, unlike the
      calyx of Held, at the PF->PC synapse either PKCalpha or PKCbeta alone is
      sufficient to mediate PTP, and if both isoforms are eliminated a compensatory PKC
      independent mechanism preserves the plasticity. These results suggest that a
      feedback mechanism allows granule cells to maintain the normal properties of
      short-term synaptic plasticity even when the mechanism that mediates PTP in wild
      type mice is eliminated.

PMID- 22993421
TI  - In for a penny, in for a pound: methylphenidate reduces the inhibitory effect of
      high stakes on persistent risky choice.
AB  - Methylphenidate (MPH) is a stimulant that increases extracellular levels of
      dopamine and noradrenaline. It can diminish risky decision-making tendencies in
      certain clinical populations. MPH is also used, without license, by healthy
      adults, but the impact on their decision-making is not well established. Previous
      work has found that dopamine receptor activity of healthy adults can modulate the
      influence of stake magnitude on decisions to persistently gamble after incurring
      a loss. In this study, we tested for modulation of this effect by MPH in 40
      healthy human adults. In a double-blind experiment, 20 subjects received 20 mg of
      MPH, while 20 matched controls received a placebo. All were provided with 30
      rounds of opportunities to accept an incurred loss from their assets or opt for a
      "double-or-nothing" gamble that would either avoid or double it. Rounds began
      with a variable loss that would double with every failed gamble until it was
      accepted, recovered, or reached a specified maximum. Probability of recovery on
      any gamble was low and ambiguous. Subjects receiving placebo gambled less as the
      magnitude of the stake was raised and as the magnitude of accumulated loss
      escalated over the course of the task. In contrast, subjects treated with MPH
      gambled at a consistent rate, well above chance, across all stakes and trials.
      Trait reward responsiveness also reduced the impact of high stakes. The findings
      suggest that elevated catecholamine activity by MPH can disrupt inhibitory
      influences on persistent risky choice in healthy adults.

PMID- 22993420
TI  - Jedi-1 and MEGF10 signal engulfment of apoptotic neurons through the tyrosine
      kinase Syk.
AB  - During the development of the peripheral nervous system there is extensive
      apoptosis, and these neuronal corpses need to be cleared to prevent an
      inflammatory response. Recently, Jedi-1 and MEGF10, both expressed in glial
      precursor cells, were identified in mouse as having an essential role in this
      phagocytosis (Wu et al., 2009); however, the mechanisms by which they promote
      engulfment remained unknown. Both Jedi-1 and MEGF10 are homologous to the
      Drosophila melanogaster receptor Draper, which mediates engulfment through
      activation of the tyrosine kinase Shark. Here, we identify Syk, the mammalian
      homolog of Shark, as a signal transducer for both Jedi-1 and MEGF10. Syk
      interacted with each receptor independently through the immunoreceptor tyrosine
      based activation motifs (ITAMs) in their intracellular domains. The interaction
      was enhanced by phosphorylation of the tyrosines in the ITAMs by Src family
      kinases (SFKs). Jedi association with Syk and activation of the kinase was also
      induced by exposure to dead cells. Expression of either Jedi-1 or MEGF10 in HeLa
      cells facilitated engulfment of carboxylated microspheres to a similar extent,
      and there was no additive effect when they were coexpressed. Mutation of the ITAM
      tyrosines of Jedi-1 and MEGF10 prevented engulfment. The SFK inhibitor PP2 or a
      selective Syk inhibitor (BAY 61-3606) also blocked engulfment. Similarly, in
      cocultures of glial precursors and dying sensory neurons from embryonic mice,
      addition of PP2 or knock down of endogenous Syk decreased the phagocytosis of
      apoptotic neurons. These results indicate that both Jedi-1 and MEGF10 can mediate
      phagocytosis independently through the recruitment of Syk.

PMID- 22993422
TI  - MSK1 regulates homeostatic and experience-dependent synaptic plasticity.
AB  - The ability of neurons to modulate synaptic strength underpins synaptic
      plasticity, learning and memory, and adaptation to sensory experience. Despite
      the importance of synaptic adaptation in directing, reinforcing, and revising the
      behavioral response to environmental influences, the cellular and molecular
      mechanisms underlying synaptic adaptation are far from clear. Brain-derived
      neurotrophic factor (BDNF) is a prime initiator of structural and functional
      synaptic adaptation. However, the signaling cascade activated by BDNF to initiate
      these adaptive changes has not been elucidated. We have previously shown that
      BDNF activates mitogen- and stress-activated kinase 1 (MSK1), which regulates
      gene transcription via the phosphorylation of both CREB and histone H3. Using
      mice with a kinase-dead knock-in mutation of MSK1, we now show that MSK1 is
      necessary for the upregulation of synaptic strength in response to environmental
      enrichment in vivo. Furthermore, neurons from MSK1 kinase-dead mice failed to
      show scaling of synaptic transmission in response to activity deprivation in
      vitro, a deficit that could be rescued by reintroduction of wild-type MSK1. We
      also show that MSK1 forms part of a BDNF- and MAPK-dependent signaling cascade
      required for homeostatic synaptic scaling, which likely resides in the ability of
      MSK1 to regulate cell surface GluA1 expression via the induction of Arc/Arg3.1.
      These results demonstrate that MSK1 is an integral part of a signaling pathway
      that underlies the adaptive response to synaptic and environmental experience.
      MSK1 may thus act as a key homeostat in the activity- and experience-dependent
      regulation of synaptic strength.

PMID- 22993423
TI  - Dissection of gain control mechanisms in Drosophila mechanotransduction.
AB  - Mechanoreceptor cells respond to a vast span of stimulus intensities, which they
      transduce into a limited response-range using a dynamic regulation of
      transduction gain. Weak stimuli are detected by enhancing the gain of responses
      through the process of active mechanical amplification. To preserve
      responsiveness, the gain of responses to prolonged activation is rapidly reduced
      through the process of adaptation. We investigated long-term processes of
      mechanotransduction gain control by studying responses from single
      mechanoreceptor neurons in Drosophila. We found that mechanical stimuli elicited
      a sustained reduction of gain that we termed long-term adaptation. Long-term
      adaptation and the adaptive decay of responses during stimuli had distinct
      kinetics and they were independently affected by manipulations of
      mechanotransduction. Therefore, long-term adaptation is not associated with the
      reduction of response gain during stimulation. Instead, the long-term adaptation
      suppressed canonical features of active amplification which were the high gain of
      weak stimuli and the spontaneous emission of noise. In addition, depressing
      amplification using energy deprivation recapitulated the effects of long-term
      adaptation. These data suggest that long-term adaptation is mediated by
      suppression of active amplification. Finally, the extent of long-term adaptation
      matched with cytoplasmic Ca(2+) levels and dTrpA1-induced Ca(2+) elevation
      elicited the effects of long-term adaptation. Our data suggest that
      mechanotransduction employs parallel adaptive mechanisms: while a rapid process
      exerts immediate gain reduction, long-term adjustments are achieved by
      attenuating active amplification. The slow adjustment of gain, manifest as
      diminished sensitivity, is associated with the accumulation of Ca(2+).

PMID- 22993425
TI  - A parametric investigation of pattern separation processes in the medial temporal
      lobe.
AB  - The hippocampus is thought to be involved in memory formation and consolidation,
      with computational models proposing the process of pattern separation as a means
      for encoding overlapping memories. Previous research has used semantically
      related targets and lures to investigate hippocampal responses to mnemonic
      interference. Here, we attempted to define the response function of the human
      hippocampus and its inputs during pattern separation by parametrically varying
      target-lure similarity in a continuous recognition task. We also investigated the
      effect of task demands (intentional vs incidental encoding) on pattern separation
      processes. We collected functional magnetic resonance imaging data while
      participants were shown a series of objects. In the intentional paradigm,
      participants identified objects as "new" (novel stimuli), "old" (exact
      repetitions), or "rotated" (previously seen objects that were subsequently
      rotated by varied degrees). In the incidental paradigm, participants were shown
      the same stimuli but identified objects as "toy" or "not toy." Activation in the
      hippocampus was best fit with a power function, consistent with predictions made
      by computational models of pattern separation processes in the hippocampus. The
      degree of pattern separation was driven by the information most relevant to the
      task: pattern separation was seen in the left hippocampus when semantic
      information was more important to the task and seen in the right hippocampus when
      spatial information was more important. We also present data illustrating that
      top-down processes modulate activity in the ventral visual processing stream.

PMID- 22993426
TI  - A role for silent synapses in the development of the pathway from layer 2/3 to 5
      pyramidal cells in the neocortex.
AB  - The integration of neurons within the developing cerebral cortex is a prolonged
      process dependent on a combination of molecular and physiological cues. To
      examine the latter we used laser scanning photostimulation (LSPS) of caged
      glutamate in conjunction with whole-cell patch-clamp electrophysiology to probe
      the integration of pyramidal cells in the sensorimotor regions of the mouse
      neocortex. In the days immediately after postnatal day 5 (P5) the origin of the
      LSPS-evoked AMPA receptor (AMPAR)-mediated synaptic inputs were diffuse and
      poorly defined with considerable variability between cells. Over the subsequent
      week this coalesced and shifted, primarily influenced by an increased
      contribution from layers 2/3 cells, which became a prominent motif of the
      afferent input onto layer 5 pyramidal cells regardless of cortical region. To
      further investigate this particular emergent translaminar connection, we
      alternated our mapping protocol between two holding potentials (-70 and +40 mV)
      allowing us to detect exclusively NMDA receptor (NMDAR)-mediated inputs. This
      revealed distal MK-801-sensitive synaptic inputs that predict the formation of
      the mature, canonical layer 2/3 to 5 pathway. However, these were a transient
      feature and had been almost entirely converted to AMPAR synapses at a later age
      (P16). To examine the role of activity in the recruitment of early NMDAR
      synapses, we evoked brief periods (20 min) of rhythmic bursting. Short intense
      periods of activity could cause a prolonged augmentation of the total input onto
      pyramidal cells up until P12; a time point when the canonical circuit has been
      instated and synaptic integration shifts to a more consolidatory phase.

PMID- 22993424
TI  - GABAergic inhibition of histaminergic neurons regulates active waking but not the
      sleep-wake switch or propofol-induced loss of consciousness.
AB  - The activity of histaminergic neurons in the tuberomammillary nucleus (TMN) of
      the hypothalamus correlates with an animal's behavioral state and maintains
      arousal. We examined how GABAergic inputs onto histaminergic neurons regulate
      this behavior. A prominent hypothesis, the "flip-flop" model, predicts that
      increased and sustained GABAergic drive onto these cells promotes sleep.
      Similarly, because of the histaminergic neurons' key hub-like place in the
      arousal circuitry, it has also been suggested that anesthetics such as propofol
      induce loss of consciousness by acting primarily at histaminergic neurons. We
      tested both these hypotheses in mice by genetically removing ionotropic GABA(A)
      or metabotropic GABA(B) receptors from histidine decarboxylase-expressing
      neurons. At the cellular level, histaminergic neurons deficient in synaptic
      GABA(A) receptors were significantly more excitable and were insensitive to the
      anesthetic propofol. At the behavioral level, EEG profiles were recorded in
      nontethered mice over 24 h. Surprisingly, GABAergic transmission onto
      histaminergic neurons had no effect in regulating the natural sleep-wake cycle
      and, in the case of GABA(A) receptors, for propofol-induced loss of righting
      reflex. The latter finding makes it unlikely that the histaminergic TMN has a
      central role in anesthesia. GABA(B) receptors on histaminergic neurons were
      dispensable for all behaviors examined. Synaptic inhibition of histaminergic
      cells by GABA(A) receptors, however, was essential for habituation to a novel
      environment.

PMID- 22993427
TI  - Astrocyte-derived thrombospondins mediate the development of hippocampal
      presynaptic plasticity in vitro.
AB  - Astrocytes contribute to many neuronal functions, including synaptogenesis, but
      their role in the development of synaptic plasticity remains unclear. Presynaptic
      muting of hippocampal glutamatergic terminals defends against excitotoxicity.
      Here we studied the role of astrocytes in the development of presynaptic muting
      at glutamatergic synapses in rat hippocampal neurons. We found that astrocytes
      were critical for the development of depolarization-dependent and G(i/o)
      dependent presynaptic muting. The ability of cAMP analogues to modulate
      presynaptic function was also impaired by astrocyte deficiency. Although
      astrocyte deprivation resulted in postsynaptic glutamate receptor deficits, this
      effect appeared independent of astrocytes' role in presynaptic muting. Muting was
      restored with chronic, but not acute, treatment with astrocyte-conditioned
      medium, indicating that a soluble factor is permissive for muting. Astrocyte
      derived thrombospondins (TSPs) are likely responsible because TSP1 mimicked the
      effect of conditioned medium, and gabapentin, a high-affinity antagonist of TSP
      binding to the alpha2delta-1 calcium channel subunit, mimicked astrocyte
      deprivation. We found evidence that protein kinase A activity is abnormal in
      astrocyte-deprived neurons but restored by TSP1, so protein kinase A dysfunction
      may provide a mechanism by which muting is disrupted during astrocyte deficiency.
      In summary our results suggest an important role for astrocyte-derived TSPs,
      acting through alpha2delta-1, in maturation of a potentially important form of
      presynaptic plasticity.

PMID- 22993428
TI  - Learning and memory deficits consequent to reduction of the fragile X mental
      retardation protein result from metabotropic glutamate receptor-mediated
      inhibition of cAMP signaling in Drosophila.
AB  - Loss of the RNA-binding fragile X protein [fragile X mental retardation protein
      (FMRP)] results in a spectrum of cognitive deficits, the fragile X syndrome
      (FXS), while aging individuals with decreased protein levels present with a
      subset of these symptoms and tremor. The broad range of behavioral deficits
      likely reflects the ubiquitous distribution and multiple functions of the
      protein. FMRP loss is expected to affect multiple neuronal proteins and
      intracellular signaling pathways, whose identity and interactions are essential
      in understanding and ameliorating FXS symptoms. We used heterozygous mutants and
      targeted RNA interference-mediated abrogation in Drosophila to uncover molecular
      pathways affected by FMRP reduction. We present evidence that FMRP loss results
      in excess metabotropic glutamate receptor (mGluR) activity, attributable at least
      in part to elevation of the protein in affected neurons. Using high-resolution
      behavioral, genetic, and biochemical analyses, we present evidence that excess
      mGluR upon FMRP attenuation is linked to the cAMP decrement reported in patients
      and models, and underlies olfactory associative learning and memory deficits.
      Furthermore, our data indicate positive transcriptional regulation of the fly
      fmr1 gene by cAMP, via protein kinase A, likely through the transcription factor
      CREB. Because the human Fmr1 gene also contains CREB binding sites, the
      interaction of mGluR excess and cAMP signaling defects we present suggests novel
      combinatorial pharmaceutical approaches to symptom amelioration upon FMRP
      attenuation.

PMID- 22993429
TI  - Abca1 deficiency affects Alzheimer's disease-like phenotype in human ApoE4 but
      not in ApoE3-targeted replacement mice.
AB  - ATP-binding cassette transporter A1 (ABCA1) transporter regulates cholesterol
      efflux and is an essential mediator of high-density lipoprotein (HDL) formation.
      In amyloid precursor protein (APP) transgenic mice, Abca1 deficiency increased
      amyloid deposition in the brain paralleled by decreased levels of Apolipoprotein
      E (ApoE). The APOEepsilon4 allele is the major genetic risk factor of sporadic
      Alzheimer's disease (AD). Here, we reveal the effect of Abca1 deficiency on
      phenotype in mice expressing human ApoE3 or ApoE4. We used APP/E3 and APP/E4 mice
      generated by crossing APP/PS1DeltaE9 transgenic mice to human APOE3- and APOE4
      targeted replacement mice and examined Abca1 gene dose effect on amyloid
      deposition and cognition. The results from two behavior tests demonstrate that
      lack of one copy of Abca1 significantly exacerbates memory deficits in
      APP/E4/Abca1(-/+) but not in APP/E3/Abca1(-/+) mice. The data for amyloid plaques
      and insoluble amyloid-beta (Abeta) also show that Abca1 hemizygosity increases
      Abeta deposition only in APP/E4/Abca1(-/+) but not in APP/E3/Abca1(-/+) mice. Our
      in vivo microdialysis assays indicate that Abca1 deficiency significantly
      decreases Abeta clearance in ApoE4-expressing mice, while the effect of Abca1 on
      Abeta clearance in ApoE3-expressing mice was insignificant. In addition, we
      demonstrate that plasma HDL and Abeta42 levels in APP/E4/Abca1(-/+) mice are
      significantly decreased, and there is a negative correlation between plasma HDL
      and amyloid plaques in brain, suggesting that plasma lipoproteins may be involved
      in Abeta clearance. Overall, our results prove that the presence of functional
      Abca1 significantly influences the phenotype of APP mice expressing human ApoE4
      and further substantiate therapeutic approaches in AD based on ABCA1-APOE
      regulatory axis.

PMID- 22993430
TI  - Normal aging alters learning and attention-related teaching signals in
      basolateral amygdala.
AB  - Normal aging has been associated with an increased propensity to wait for
      rewards. When this is tested experimentally, rewards are typically offered at
      increasing delays. In this setting, persistent responding for delayed rewards in
      aged rats could reflect either changes in the evaluation of delayed rewards or
      diminished learning, perhaps due to the loss of subcortical teaching signals
      induced by changes in reward; the loss or diminution of such teaching signals
      would result in slower learning with progressive delay of reward, which would
      appear as persistent responding. Such teaching signals have commonly been
      reported in phasic firing of midbrain dopamine neurons; however, similar signals
      have also been found in reward-responsive neurons in the basolateral amygdala
      (ABL). Unlike dopaminergic teaching signals, those in ABL seem to reflect
      surprise, increasing when reward is either better or worse than expected.
      Accordingly, activity is correlated with attentional responses and with the speed
      of learning after surprising increases or decreases in reward. Here we examined
      whether these attention-related teaching signals might be altered in normal
      aging. Young (3-6 months) and aged (22-26 months) male Long-Evans rats were
      trained on a discounting task used previously to demonstrate these signals. As
      expected, aged rats were less sensitive to delays, and this change was associated
      with a loss of attentional changes in orienting behavior and neural activity.
      These results indicate that normal aging alters teaching signals in the ABL.
      Changes in these teaching signals may contribute to a host of age-related
      cognitive changes.

PMID- 22993431
TI  - Spinal cord injury induces serotonin supersensitivity without increasing
      intrinsic excitability of mouse V2a interneurons.
AB  - Denervation-induced plastic changes impair locomotor recovery after spinal cord
      injury (SCI). Spinal motoneurons become hyperexcitable after SCI, but the plastic
      responses of locomotor network interneurons (INs) after SCI have not been
      studied. Using an adult mouse SCI model, we analyzed the effects of complete
      spinal cord lesions on the intrinsic electrophysiological properties,
      excitability, and neuromodulatory responses to serotonin (5-HT) in mouse lumbar
      V2a spinal INs, which help regulate left-right alternation during locomotion.
      Four weeks after SCI, V2a INs showed almost no changes in baseline excitability
      or action potential properties; the only parameter that changed was a reduced
      input resistance. However, V2a INs became 100- to 1000-fold more sensitive to 5
      HT. Immunocytochemical analysis showed that SCI caused a coordinated loss of
      serotonergic fibers and the 5-HT transporter (SERT). Blocking the SERT with
      citalopram in intact mice did not increase 5-HT sensitivity to the level seen
      after SCI. SCI also evoked an increase in 5-HT(2C) receptor cluster number and
      intensity, suggesting that several plastic changes cooperate in increasing 5-HT
      sensitivity. Our results suggest that different components of the spinal neuronal
      network responsible for coordinating locomotion are differentially affected by
      SCI, and highlight the importance of understanding these changes when considering
      therapies targeted at functional recovery.

PMID- 22993433
TI  - Neurobiological mechanisms underlying the blocking effect in aversive learning.
AB  - Current theories of classical conditioning assume that learning depends on the
      predictive relationship between events, not just on their temporal contiguity.
      Here we employ the classic experiment substantiating this reasoning-the blocking
      paradigm-in combination with functional magnetic resonance imaging (fMRI) to
      investigate whether human amygdala responses in aversive learning conform to
      these assumptions. In accordance with blocking, we demonstrate that significantly
      stronger behavioral and amygdala responses are evoked by conditioned stimuli that
      are predictive of the unconditioned stimulus than by conditioned stimuli that
      have received the same pairing with the unconditioned stimulus, yet have no
      predictive value. When studying the development of this effect, we not only
      observed that it was related to the strength of previous conditioned responses,
      but also that predictive compared with nonpredictive conditioned stimuli received
      more overt attention, as measured by fMRI-concurrent eye tracking, and that this
      went along with enhanced amygdala responses. We furthermore observed that
      prefrontal regions play a role in the development of the blocking effect:
      ventromedial prefrontal cortex (subgenual anterior cingulate) only exhibited
      responses when conditioned stimuli had to be established as nonpredictive for an
      outcome, whereas dorsolateral prefrontal cortex also showed responses when
      conditioned stimuli had to be established as predictive. Most importantly,
      dorsolateral prefrontal cortex connectivity to amygdala flexibly switched between
      positive and negative coupling, depending on the requirements posed by predictive
      relationships. Together, our findings highlight the role of predictive value in
      explaining amygdala responses and identify mechanisms that shape these responses
      in human fear conditioning.

PMID- 22993432
TI  - Peripheral ammonia as a mediator of methamphetamine neurotoxicity.
AB  - Ammonia is metabolized by the liver and has established neurological effects. The
      current study examined the possibility that ammonia contributes to the neurotoxic
      effects of methamphetamine (METH). The results show that a binge dosing regimen
      of METH to the rat increased plasma and brain ammonia concentrations that were
      paralleled by evidence of hepatotoxicity. The role of peripheral ammonia in the
      neurotoxic effects of METH was further substantiated by the demonstration that
      the enhancement of peripheral ammonia excretion blocked the increases in brain
      and plasma ammonia and attenuated the long-term depletions of dopamine and
      serotonin typically produced by METH. Conversely, the localized perfusion of
      ammonia in combination with METH, but not METH alone or ammonia alone, into the
      striatum recapitulated the neuronal damage produced by the systemic
      administration of METH. Furthermore, this damage produced by the local
      administration of ammonia and METH was blocked by the GYKI 52466 [4-(8-methyl-9H
      1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzamine hydrochloride], an AMPA
      receptor antagonist. These findings highlight the importance of ammonia derived
      from the periphery as a small-molecule mediator of METH neurotoxicity and more
      broadly emphasize the importance of peripheral organ damage as a possible
      mechanism that mediates the neuropathology produced by drugs of abuse and other
      neuroactive molecules.

PMID- 22993434
TI  - Activity-dependent modulation of the interaction between CaMKIIalpha and Abi1 and
      its involvement in spine maturation.
AB  - Remodeling of dendritic spines through regulation of actin dynamics is a key
      event in activity-dependent structural plasticity. However, the molecular
      mechanism underlying this process is poorly understood. Here, we show that
      activity-dependent modulation of Abl interactor 1-Ca(2+)/calmodulin-dependent
      kinase IIalpha (Abi1-CaMKIIalpha) interaction, and thereby their activity, is
      important for regulation of spine morphology in cultured rat hippocampal neurons.
      Abi1 interacts with CaMKIIalpha at resting conditions through Abi1's tSNARE
      (target membrane-associated SNARE), which harbors striking homology with
      CaMKIIalpha regulatory domain. The interaction of the two proteins, Abi1 and
      CaMKIIalpha, results in their simultaneous inhibition, inhibition of CaMKIIalpha
      activity, and also inhibition of Abi1-dependent Rac activation. Their functional
      impediment is released when they dissociate from each other by calmodulin binding
      through glutamate receptor activation. Before dissociation, Abi1 is
      phosphorylated by CaMKIIalpha at serine 88, which may involve in regulation of
      Rac activation and spine maturation. Our results suggest that modulation of the
      interaction between Abi1 and CaMKIIalpha, through the glutamate receptor pathway,
      may be a molecular mechanism underlying activity-regulated structural plasticity
      in rat hippocamapal neurons.

PMID- 22993435
TI  - Cell type-specific, presynaptic LTP of inhibitory synapses on fast-spiking
      GABAergic neurons in the mouse visual cortex.
AB  - Properties and plasticity of inhibitory synapses on fast-spiking (FS) GABAergic
      (FS-GABA) interneurons in layer II/III of the mouse visual cortex were examined
      in cortical slices by whole-cell recordings of IPSCs or IPSPs evoked by
      activation of presynaptic FS or non-FS GABAergic interneurons. Unitary IPSCs
      (uIPSCs) evoked by action potentials of FS-GABA neurons have shorter onset
      latency, faster rising slope, higher peak amplitude, and faster decay time than
      those evoked by action potentials of non-FS-GABA neurons. Tetanic activation of
      presynaptic FS-GABA neurons induced long-term potentiation (LTP) of uIPSCs,
      whereas that of presynaptic non-FS-GABA neurons did not induce LTP, indicating
      that long-term plasticity of inhibitory synapses on FS-GABA neurons is pathway
      specific. For further analysis of inhibitory synaptic plasticity, IPSPs evoked by
      electrical stimulation of an adjacent site in the cortex were recorded from FS
      GABA neurons. Theta burst stimulation induced LTP of IPSPs in 12 of 14 FS-GABA
      neurons. The paired-pulse stimulation protocol and coefficient of variation
      analysis indicated that this form of LTP may be presynaptic in origin. Filling
      postsynaptic cells with a Ca(2+) chelator did not block the induction of LTP,
      suggesting no involvement of postsynaptic Ca(2+) rise. Also, this form of LTP was
      dependent neither on metabotropic glutamate receptors nor voltage-gated Ca(2+)
      channels of the L and T types. Further pharmacological analysis indicated that
      voltage-gated Ca(2+) channels other than the P/Q type, such as N and R types,
      were not involved in LTP, suggesting that P/Q-type channels are a candidate for
      factors inducing LTP of inhibitory synapses between FS-GABA neurons.

PMID- 22993436
TI  - The balance between receptor recycling and trafficking toward lysosomes
      determines synaptic strength during long-term depression.
AB  - The strength of excitatory synaptic transmission depends partly on the number of
      AMPA receptors (AMPARs) at the postsynaptic surface and, thus, can be modulated
      by membrane trafficking events. These processes are critical for some forms of
      synaptic plasticity, such as long-term potentiation and long-term depression
      (LTD). In the case of LTD, AMPARs are internalized and dephosphorylated in
      response to NMDA receptor activation. However, the fate of the internalized
      receptors upon LTD induction and its relevance for synaptic function is still a
      matter of debate. Here we examined the functional contribution of receptor
      recycling versus degradation for LTD in rat hippocampal slices, and their
      correlation with receptor dephosphorylation. We observed that GluA1 undergoes
      sequential dephosphorylation and degradation in lysosomes after LTD induction.
      However, this degradation does not have functional consequences for the
      regulation of synaptic strength, and therefore, for the expression of LTD. In
      contrast, the partition of internalized AMPARs between Rab7-dependent trafficking
      (toward lysosomes) or Rab11-dependent endosomes (recycling back toward synapses)
      is the key factor determining the extent of synaptic depression upon LTD
      induction. This sorting decision is related to the phosphorylation status of
      GluA1 Ser845, the dephosphorylated receptors being those preferentially targeted
      for lysosomal degradation. Altogether, these new data contribute to clarify the
      fate of AMPARs during LTD and emphasize the importance of membrane sorting
      decisions to determine the outcome of synaptic plasticity.

PMID- 22993438
TI  - Relationships between the firing of identified striatal interneurons and
      spontaneous and driven cortical activities in vivo.
AB  - The striatum is comprised of medium-sized spiny projection neurons (MSNs) and
      several types of interneuron, and receives massive glutamatergic input from the
      cerebral cortex. Understanding of striatal function requires definition of the
      electrophysiological properties of neurochemically identified interneurons
      sampled in the same context of ongoing cortical activity in vivo. To address
      this, we recorded the firing of cholinergic interneurons (expressing choline
      acetyltransferase; ChAT) and GABAergic interneurons expressing parvalbumin (PV)
      or nitric oxide synthase (NOS), as well as MSNs, in anesthetized rats during
      cortically defined brain states. Depending on the cortical state, these
      interneurons were partly distinguished from each other, and MSNs, on the basis of
      firing rate and/or pattern. During slow-wave activity (SWA), ChAT+ interneurons,
      and some PV+ and NOS+ interneurons, were tonically active; NOS+ interneurons
      fired prominent bursts but, contrary to investigations in vitro, these were not
      typical low-threshold spike bursts. Identified MSNs, and other PV+ and NOS+
      interneurons, were phasically active. Contrasting with ChAT+ interneurons, whose
      firing showed poor brain state dependency, PV+ and NOS+ interneurons displayed
      robust firing increases and decreases, respectively, upon spontaneous or driven
      transitions from SWA to cortical activation. The firing of most neurons was phase
      locked to cortical slow oscillations, but only PV+ and ChAT+ interneurons also
      fired in time with cortical spindle and gamma oscillations. Complementing this
      diverse temporal coupling, each interneuron type exhibited distinct responses to
      cortical stimulation. Thus, these striatal interneuron types have distinct
      temporal signatures in vivo, including relationships to spontaneous and driven
      cortical activities, which likely underpin their specialized contributions to
      striatal microcircuit function.

PMID- 22993439
TI  - Reaching the limit of the oculomotor plant: 3D kinematics after abducens nerve
      stimulation during the torsional vestibulo-ocular reflex.
AB  - Accumulating evidence shows that the oculomotor plant is capable of implementing
      aspects of three-dimensional kinematics such as Listing's law and the half-angle
      rule. But these studies have only examined the eye under static conditions or
      with movements that normally obey these rules (e.g., saccades and pursuit). Here
      we test the capability of the oculomotor plant to rearrange itself as necessary
      for non-half-angle behavior. Three monkeys (Macaca mulatta) fixated five
      vertically displaced targets along the midsagittal plane while sitting on a
      motion platform that rotated sinusoidally about the naso-occipital axis. This
      activated the torsional, rotational vestibulo-ocular reflex, which exhibits a
      zero-angle or negative-angle rule (depending on the visual stimulus). On random
      sinusoidal cycles, we stimulated the abducens nerve and observed the resultant
      eye movements. If the plant has rearranged itself to implement this non-half
      angle behavior, then stimulation should reveal this behavior. On the other hand,
      if the plant is only capable of half-angle behavior, then stimulation should
      reveal a half-angle rule. We find the latter to be true and therefore additional
      neural signals are likely necessary to implement non-half-angle behavior.

PMID- 22993440
TI  - Histamine release in the basal forebrain mediates cortical activation through
      cholinergic neurons.
AB  - The basal forebrain (BF) is a key structure in regulating both cortical activity
      and sleep homeostasis. It receives input from all ascending arousal systems and
      is particularly highly innervated by histaminergic neurons. Previous studies
      clearly point to a role for histamine as a wake-promoting substance in the BF. We
      used in vivo microdialysis and pharmacological treatments in rats to study which
      electroencephalogram (EEG) spectral properties are associated with histamine
      induced wakefulness and whether this wakefulness is followed by increased sleep
      and increased EEG delta power during sleep. We also investigated which BF neurons
      mediate histamine-induced cortical activation. Extracellular BF histamine levels
      rose immediately and remained constant throughout a 6 h period of sleep
      deprivation, returning to baseline levels immediately afterward. During the
      spontaneous sleep-wake cycle, we observed a strong correlation between
      wakefulness and extracellular histamine concentrations in the BF, which was
      unaffected by the time of day. The perfusion of histamine into the BF increased
      wakefulness and cortical activity without inducing recovery sleep. The perfusion
      of a histamine receptor 1 antagonist into the BF decreased both wakefulness and
      cortical activity. Lesioning the BF cholinergic neurons abolished these effects.
      Together, these results show that activation of the cholinergic BF by histamine
      is important in sustaining a high level of cortical activation, and that a lack
      of activation of the cholinergic BF by histamine may be important in initiating
      and maintaining nonrapid eye movement sleep. The level of histamine release is
      tightly connected to behavioral state, but conveys no information about sleep
      pressure.

PMID- 22993437
TI  - Dependence of regenerated sensory axons on continuous neurotrophin-3 delivery.
AB  - Previous studies have shown that injured dorsal column sensory axons extend
      across a spinal cord lesion site if axons are guided by a gradient of
      neurotrophin-3 (NT-3) rostral to the lesion. Here we examined whether continuous
      NT-3 delivery is necessary to sustain regenerated axons in the injured spinal
      cord. Using tetracycline-regulated (tet-off) lentiviral gene delivery, NT-3
      expression was tightly controlled by doxycycline administration. To examine axon
      growth responses to regulated NT-3 expression, adult rats underwent a C3 dorsal
      funiculus lesion. The lesion site was filled with bone marrow stromal cells, tet
      off-NT-3 virus was injected rostral to the lesion site, and the intrinsic growth
      capacity of sensory neurons was activated by a conditioning lesion. When NT-3
      gene expression was turned on, cholera toxin beta-subunit-labeled sensory axons
      regenerated into and beyond the lesion/graft site. Surprisingly, the number of
      regenerated axons significantly declined when NT-3 expression was turned off,
      whereas continued NT-3 expression sustained regenerated axons. Quantification of
      axon numbers beyond the lesion demonstrated a significant decline of axon growth
      in animals with transient NT-3 expression, only some axons that had regenerated
      over longer distance were sustained. Regenerated axons were located in white
      matter and did not form axodendritic synapses but expressed presynaptic markers
      when closely associated with NG2-labeled cells. A decline in axon density was
      also observed within cellular grafts after NT-3 expression was turned off
      possibly via reduction in L1 and laminin expression in Schwann cells. Thus,
      multiple mechanisms underlie the inability of transient NT-3 expression to fully
      sustain regenerated sensory axons.

PMID- 22993441
TI  - PrP(C) homodimerization stimulates the production of PrPC cleaved fragments PrPN1
      and PrPC1.
AB  - An endoproteolytic cleavage termed alpha-cleavage between residues 111/112 is a
      characteristic feature of the cellular prion protein (PrP(C)). This cleavage
      generates a soluble N-terminal fragment (PrPN1) and a
      glycosylphosphatidylinositol-anchored C-terminal fragment (PrPC1). Independent
      studies demonstrate that modulating PrP(C) alpha-cleavage represents a potential
      therapeutic strategy in prion diseases. The regulation of PrP(C) alpha-cleavage
      is unclear. The only known domain that is essential for the alpha-cleavage to
      occur is a hydrophobic domain (HD). Importantly, the HD is also essential for the
      formation of PrP(C) homodimers. To explore the role of PrP(C) homodimerization on
      the alpha-cleavage, we used a well described inducible dimerization strategy
      whereby a chimeric PrP(C) composed of a modified FK506-binding protein (Fv) fused
      with PrP(C) and termed Fv-PrP is incubated in the presence of a dimerizer AP20187
      ligand. We show that homodimerization leads to a considerable increase of PrP(C)
      alpha-cleavage in cultured cells and release of PrPN1 and PrPC1. Interestingly,
      enforced homodimerization increased PrP(C) levels at the plasma membrane, and
      preventing PrP(C) trafficking to the cell surface inhibited dimerization-induced
      alpha-cleavage. These observations were confirmed in primary hippocampal neurons
      from transgenic mice expressing Fv-PrP. The proteases responsible for the alpha
      cleavage are still elusive, and in contrast to initial studies we confirm more
      recent investigations that neither ADAM10 nor ADAM17 are involved. Importantly,
      PrPN1 produced after PrP(C) homodimerization protects against toxic amyloid-beta
      (Abeta) oligomers. Thus, our results show that PrP(C) homodimerization is an
      important regulator of PrP(C) alpha-cleavage and may represent a potential
      therapeutic avenue against Abeta toxicity in Alzheimer's disease.

PMID- 22993442
TI  - Two seizure-onset types reveal specific patterns of high-frequency oscillations
      in a model of temporal lobe epilepsy.
AB  - High-frequency oscillations (HFOs; 80-500 Hz) are thought to mirror the
      pathophysiological changes occurring in epileptic brains. However, the
      distribution of HFOs during seizures remains undefined. Here, we recorded from
      the hippocampal CA3 subfield, subiculum, entorhinal cortex, and dentate gyrus to
      quantify the occurrence of ripples (80-200 Hz) and fast ripples (250-500 Hz)
      during low-voltage fast-onset (LVF) and hypersynchronous-onset (HYP) seizures in
      the rat pilocarpine model of temporal lobe epilepsy. We discovered in LVF
      seizures that (1) progression from preictal to ictal activity was characterized
      in seizure-onset zones by an increase of ripple rates that were higher when
      compared with fast ripple rates and (2) ripple rates during the ictal period were
      higher compared with fast ripple rates in seizure-onset zones and later in
      regions of secondary spread. In contrast, we found in HYP seizures that (1) fast
      ripple rates increased during the preictal period and were higher compared with
      ripple rates in both seizure-onset zones and in regions of secondary spread and
      (2) they were still higher compared with ripple rates in both seizure-onset zones
      and regions of secondary spread during the ictal period. Our findings demonstrate
      that ripples and fast ripples show distinct time- and region-specific patterns
      during LVF and HYP seizures, thus suggesting that they play specific roles in
      ictogenesis.

PMID- 22993443
TI  - Learning of new sound categories shapes neural response patterns in human
      auditory cortex.
AB  - The formation of new sound categories is fundamental to everyday goal-directed
      behavior. Categorization requires the abstraction of discrete classes from
      continuous physical features as required by context and task. Electrophysiology
      in animals has shown that learning to categorize novel sounds alters their
      spatiotemporal neural representation at the level of early auditory cortex.
      However, functional magnetic resonance imaging (fMRI) studies so far did not
      yield insight into the effects of category learning on sound representations in
      human auditory cortex. This may be due to the use of overlearned speech-like
      categories and fMRI subtraction paradigms, leading to insufficient sensitivity to
      distinguish the responses to learning-induced, novel sound categories. Here, we
      used fMRI pattern analysis to investigate changes in human auditory cortical
      response patterns induced by category learning. We created complex novel sound
      categories and analyzed distributed activation patterns during passive listening
      to a sound continuum before and after category learning. We show that only after
      training, sound categories could be successfully decoded from early auditory
      areas and that learning-induced pattern changes were specific to the category
      distinctive sound feature (i.e., pitch). Notably, the similarity between fMRI
      response patterns for the sound continuum mirrored the sigmoid shape of the
      behavioral category identification function. Our results indicate that perceptual
      representations of novel sound categories emerge from neural changes at early
      levels of the human auditory processing hierarchy.

PMID- 22993444
TI  - Corelease of dopamine and GABA by a retinal dopaminergic neuron.
AB  - Numerous neurons release two transmitters of low molecular mass, but it is
      controversial whether they are localized within the same synaptic vesicle, with
      the single exception of GABA and glycine because they are ferried into the
      vesicle by the same transporter. Retinal dopaminergic (DAergic) amacrine cells
      synthesize both dopamine (DA) and GABA. Both transmitters are released over the
      entire cell surface and act on neighboring and distant neurons by volume
      transmission, but, in addition, DAergic cells establish GABAergic synapses onto
      AII amacrine cells, the neurons that transfer rod signals to cone bipolars. By
      combining recordings of DA and GABA release from isolated, genetically identified
      perikarya of DAergic cells from the mouse retina, we observed that a proportion
      of the events of DA and GABA exocytosis were simultaneous, suggesting corelease.
      Furthermore, a proportion of the secretory organelles in the perikaryon and
      synaptic endings of DAergic cells contained both vesicular transporters for DA
      [vesicular monoamine transporter 2 (VMAT2)] and GABA [vesicular GABA transporter
      (VGAT)]. Because the majority of the DA release events concerned a single
      transmitter and organelles were present that contained a single transporter,
      either VMAT2 or VGAT, we conclude that the secretory organelles of DAergic cells
      contain variable concentrations of the two transmitters, which are in turn
      determined by a variable mixture of the two transporter molecules in their
      limiting membrane. This variability can be explained if the relative numbers of
      transporter molecules is determined stochastically during the budding of the
      somatic organelles from the trans-Golgi network or the retrieval of the vesicular
      membrane from the plasmalemma after exocytosis.

PMID- 22993445
TI  - A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3
      controls neural progenitor cell-cycle exit and differentiation.
AB  - MicroRNAs have emerged as key posttranscriptional regulators of gene expression
      during vertebrate development. We show that the miR-200 family plays a crucial
      role for the proper generation and survival of ventral neuronal populations in
      the murine midbrain/hindbrain region, including midbrain dopaminergic neurons, by
      directly targeting the pluripotency factor Sox2 and the cell-cycle regulator E2F3
      in neural stem/progenitor cells. The lack of a negative regulation of Sox2 and
      E2F3 by miR-200 in conditional Dicer1 mutants (En1(+/Cre); Dicer1(flox/flox)
      mice) and after miR-200 knockdown in vitro leads to a strongly reduced cell-cycle
      exit and neuronal differentiation of ventral midbrain/hindbrain (vMH) neural
      progenitors, whereas the opposite effect is seen after miR-200 overexpression in
      primary vMH cells. Expression of miR-200 is in turn directly regulated by Sox2
      and E2F3, thereby establishing a unilateral negative feedback loop required for
      the cell-cycle exit and neuronal differentiation of neural stem/progenitor cells.
      Our findings suggest that the posttranscriptional regulation of Sox2 and E2F3 by
      miR-200 family members might be a general mechanism to control the transition
      from a pluripotent/multipotent stem/progenitor cell to a postmitotic and more
      differentiated cell.

PMID- 22993446
TI  - Fos activation of selective afferents to ventral tegmental area during cue
      induced reinstatement of cocaine seeking in rats.
AB  - Ventral tegmental area (VTA) dopamine neurons are crucial for appetitive
      responses to Pavlovian cues, including cue-induced reinstatement of drug seeking.
      However, it is unknown which VTA inputs help activate these neurons, transducing
      stimuli into salient cues that drive drug-seeking behavior. Here we examined 56
      VTA afferents from forebrain and midbrain that are Fos activated during cue
      induced reinstatement. We injected the retrograde tracer cholera toxin beta
      subunit (CTb) unilaterally into rostral or caudal VTA of male rats. All animals
      were trained to self-administer cocaine, then extinguished of this behavior. On a
      final test day, animals were exposed to response-contingent cocaine-associated
      cues, extinction conditions, a non-cocaine-predictive CS-, or a novel
      environment, and brains were processed to visualize CTb and Fos immunoreactivity
      to identify VTA afferents activated in relation to behaviors. VTA-projecting
      neurons in subregions of medial accumbens shell, ventral pallidum, elements of
      extended amygdala, and lateral septum (but not prefrontal cortex) were activated
      specifically during cue-induced cocaine seeking, and some of these were also
      activated proportionately to the degree of cocaine seeking. Surprisingly, though
      efferents from the lateral hypothalamic orexin field were also Fos activated
      during reinstatement, these were largely non-orexinergic. Also, VTA afferents
      from the rostromedial tegmental nucleus and lateral habenula were specifically
      activated during extinction and CS- tests, when cocaine was not expected. These
      findings point to a select set of subcortical nuclei which provide reinstatement
      related inputs to VTA, translating conditioned stimuli into cocaine-seeking
      behavior.

PMID- 22993447
TI  - Superior colliculus mediates cervical dystonia evoked by inhibition of the
      substantia nigra pars reticulata.
AB  - Cervical dystonia (CD; spasmodic torticollis) can be evoked by inhibition of
      substantia nigra pars reticulata (SNpr) in the nonhuman primate (Burbaud et al.,
      1998; Dybdal et al., 2012). Suppression of GABAergic neurons that project from
      SNpr results in the disinhibition of the targets to which these neurons project.
      It therefore should be possible to prevent CD by inhibition of the appropriate
      nigral target region(s). Here we tested the hypothesis that the deep and
      intermediate layers of the superior colliculus (DLSC), a key target of nigral
      projections, are required for the emergence of CD. To test this hypothesis, we
      pretreated the DLSC of four macaques with the GABA(A) agonist muscimol to
      determine whether this treatment would prevent CD evoked by muscimol infusions in
      SNpr. Our data supported this hypothesis: inhibition of DLSC attenuated CD evoked
      by muscimol in SNpr in all four animals. In two of the four subjects, quadrupedal
      rotations were evoked by muscimol application into SNpr sites that were distinct
      from those that induced dystonia. We found that inhibition of DLSC did not
      significantly alter quadrupedal rotations, suggesting that this response is
      dissociable from the SNpr-evoked CD. Our results are the first to demonstrate a
      role of DLSC in mediating the expression of CD. Furthermore, these data reveal a
      functional relationship between SNpr and DLSC in regulating posture and movement
      in the nonhuman primate, raising the possibility that the nigrotectal pathway has
      potential as a target for therapeutic interventions for CD.

PMID- 22993448
TI  - Non-motor symptoms in early Parkinson's disease: a 2-year follow-up study on
      previously untreated patients.
AB  - BACKGROUND: Non-motor symptoms are very common among patients with Parkinson's
      disease since the earliest stage, but little is known about their progression and
      their relationship with dopaminergic replacement therapy. METHODS: We studied non
      motor symptoms before and after 2 years from dopaminergic therapy introduction in
      ninety-one newly diagnosed previously untreated PD patients. RESULTS: At
      baseline, nearly all patients (97.8%) referred at least one non-motor symptom. At
      follow-up, only few non-motor symptoms significantly changed. Particularly,
      depression and concentration became less frequent, while weight change
      significantly increased after introduction of dopamine agonists. CONCLUSIONS: We
      reported for the first time a 2-year prospective study on non-motor symptoms
      before and after starting therapy in newly diagnosed PD patients. Even if non
      motor symptoms are very frequent in early stage, they tend to remain stable
      during the early phase of disease, being only few non-motor symptoms affected
      from dopaminergic therapy and, specifically, by the use of dopamine agonists.

PMID- 22993450
TI  - The differential diagnosis of Huntington's disease-like syndromes: 'red flags'
      for the clinician.
AB  - A growing number of progressive heredodegenerative conditions mimic the
      presentation of Huntington's disease (HD). Differentiating among these HD-like
      syndromes is necessary when a patient with a combination of movement disorders,
      cognitive decline, behavioural abnormalities and progressive disease course
      proves negative to the genetic testing for HD causative mutations, that is, IT15
      gene trinucleotide-repeat expansion. The differential diagnosis of HD-like
      syndromes is complex and may lead to unnecessary and costly investigations. We
      propose here a guide to this differential diagnosis focusing on a limited number
      of clinical features ('red flags') that can be identified through accurate
      clinical examination, collection of historical data and a few routine ancillary
      investigations. These features include the ethnic background of the patient, the
      involvement of the facio-bucco-lingual and cervical district by the movement
      disorder, the co-occurrence of cerebellar features and seizures, the presence of
      peculiar gait patterns and eye movement abnormalities, and an atypical
      progression of illness. Additional help may derive from the cognitive-behavioural
      presentation of the patient, as well as by a restricted number of ancillary
      investigations, mainly MRI and routine blood tests. These red flags should be
      constantly updated as the phenotypic characterisation and identification of more
      reliable diagnostic markers for HD-like syndromes progress over the following
      years.

PMID- 22993452
TI  - Why Wait?: The Effect of Marriage and Childbearing on the Wages of Men and Women.
AB  - We use data from the earlier and later cohorts of the NLSY to estimate the effect
      of marriage and childbearing on wages. Our estimates imply that marriage lowers
      female wages 2-4 percent in the year of marriage. Marriage also lowers the wage
      growth of men and women by about two and four percentage points, respectively. A
      first birth lowers female wages 2-3 percent, but has no effect on wage growth.
      Male wages are unaffected by childbearing. These findings suggest that early
      marriage and childbearing can lead to substantial decreases in lifetime earnings.

PMID- 22993451
TI  - Dopamine agonist withdrawal syndrome (DAWS): perils of flicking the dopamine
      'switch'.

PMID- 22993453
TI  - Preference for the Outcome That Follows a Relatively Aversive Event: Contrast or
      Delay Reduction?
AB  - Pigeons prefer a positive discriminative (S+) stimulus that follows a less
      preferred event (a large number of required responses, a longer delay, or the
      absence of food) over a different S+ with a similar history of reinforcement that
      follows a more preferred event (a single required response, no delay, or food).
      We proposed that this phenomenon results from contrast (referred to as within
      trial contrast) between the less preferred initial event and the signal for
      reinforcement. Delay reduction theory (Fantino, 1969) can account for these
      results by proposing that the less preferred initial event lengthens the duration
      of the trial, thereby allowing the S+ stimulus to occur later in the trial and
      thus become a better predictor of reinforcement. In the present experiments, we
      further explored this effect. In Experiment 1, we controlled for trial duration
      by using a fixed ratio response (30 pecks) as one initial event and the absence
      of pecking for the same duration as the other initial event (0 pecks). The
      pigeons showed a reliable preference for the positive stimulus that followed the
      least preferred initial event. In Experiment 2, we controlled for trial duration
      by using 30 pecks as one initial event and 1 peck followed by a delay that
      matched the duration of the preceding 30-peck trial. (Group Time Same). For Group
      Time Different, there was no delay following the 1-peck initial event. For Group
      Time Same, preference for the initial event negatively predicted the pigeons'
      preference for the S+ stimulus that followed, supporting the contrast account. A
      somewhat greater preference for the discriminative stimulus that followed the
      least preferred initial event was found for Group Time Different suggesting that
      in addition to contrast, delay reduction also may play a small role. However, the
      greater initial-event preference found for Group Time Different suggests that
      contrast can account for the group difference as well.

PMID- 22993454
TI  - Understanding Activist Leadership Effort in the Movement Opposing Drinking and
      Driving.
AB  - Why do some social movement leaders work harder than others? And, how does gender
      affect the patterns we uncover? Utilizing historical case study evidence of local
      chapters in the emerging movement opposing drinking and driving we are able to
      develop and test theoretical expectations about predictors of weekly effort among
      MADD and RID leaders. Taken together, our model explains 45 percent of the
      variation in leadership effort. We find bureaucratic complexity and victim
      support activities are more powerful predictors of effort than are individual
      leader characteristics, although all are important. Further analysis reveals that
      gender almost wholly conditions the strong effect of bureaucratic complexity on
      leadership effort so that increasingly complex chapter structures are associated
      with substantial increases in work hours for women but not men.

PMID- 22993449
TI  - The art of gene therapy for glioma: a review of the challenging road to the
      bedside.
AB  - Glioblastoma multiforme (GBM) is a highly invasive brain tumour that is
      unvaryingly fatal in humans despite even aggressive therapeutic approaches such
      as surgical resection followed by chemotherapy and radiotherapy. Unconventional
      treatment options such as gene therapy provide an intriguing option for curbing
      glioma related deaths. To date, gene therapy has yielded encouraging results in
      preclinical animal models as well as promising safety profiles in phase I
      clinical trials, but has failed to demonstrate significant therapeutic efficacy
      in phase III clinical trials. The most widely studied antiglioma gene therapy
      strategies are suicide gene therapy, genetic immunotherapy and oncolytic
      virotherapy, and we have attributed the challenging transition of these
      modalities into the clinic to four major roadblocks: (1) anatomical features of
      the central nervous system, (2) the host immune system, (3) heterogeneity and
      invasiveness of GBM and (4) limitations in current GBM animal models. In this
      review, we discuss possible ways to jump these hurdles and develop new gene
      therapies that may be used alone or in synergy with other modalities to provide a
      powerful treatment option for patients with GBM.

PMID- 22993455
TI  - Efficient synthesis of nucleoside aryloxy phosphoramidate prodrugs utilizing
      benzyloxycarbonyl protection.
AB  - An efficient method for the synthesis of nucleoside phosphoramidates prodrugs (6a
      f) has been developed that employs a simple protection/deprotection sequence of
      the nucleoside with benzyloxycarbonyl (Cbz). The coupling reaction of Cbz
      protected derivatives (5a-f) with phenyl-(ethoxy-L-alaninyl)-phosphorochloridate
      (7), followed by Cbz group removal by hydrogenolysis provided the phenyl
      phosphoramidate ProTides (6a-f) in excellent overall yields.

PMID- 22993457
TI  - Performance of Chlorella sorokiniana under simulated extreme winter conditions.
AB  - High annual microalgae productivities can only be achieved if solar light is
      efficiently used through the different seasons. During winter the productivity is
      low because of the light and temperature conditions. The productivity and
      photosynthetic efficiency of Chlorella sorokiniana were assessed under the worst
      case scenario found during winter time in Huelva, south of Spain. The maximum
      light intensity (800 MUmol photons m(-2) s(-1)) and temperature (20 degrees C)
      during winter were simulated in a lab-scale photobioreactor with a short light
      path of 14 mm. Chemostat conditions were applied and the results were compared
      with a temperature-controlled situation at 38 degrees C (optimal growth
      temperature for C. sorokiniana). When temperature was optimal the highest
      productivity was found at a dilution rate of 0.18 h(-1) (P(v) = 0.28 g Kg(-1) h(
      1)), and the biomass yield on light energy was high (Y(x,E) = 1.2 g mol(-1)
      photons supplied). However, at suboptimal temperature, the specific growth rate
      of C. sorokiniana was surprisingly low, not being able to support continuous
      operation at a dilution rate higher than 0.02 h(-1). The slow metabolism under
      suboptimal temperature resulted in a decline of the light energy requirements of
      the cells. Consequently, the maximum winter irradiance was experienced as
      excessive, leading to a low photosynthetic efficiency and productivity (Y(x,E) =
      0.5 g mol(-1) photons supplied, P(v) = 0.1 g Kg(-1) h(-1)). At suboptimal
      temperature a higher carotenoid-to-chlorophyll ratio was observed indicating the
      activation of light-dissipating processes. We conclude that temperature control
      and/or light dilution during winter time will enhance the productivity.

PMID- 22993458
TI  - Where are we in elimination of avoidable blindness after ten years of
      implementing 'VISION 2020 The Right to the sight' in Oman?

PMID- 22993456
TI  - Playing Music for a Smarter Ear: Cognitive, Perceptual and Neurobiological
      Evidence.
AB  - Human hearing depends on a combination of cognitive and sensory processes that
      function by means of an interactive circuitry of bottom-up and top-down neural
      pathways, extending from the cochlea to the cortex and back again. Given that
      similar neural pathways are recruited to process sounds related to both music and
      language, it is not surprising that the auditory expertise gained over years of
      consistent music practice fine-tunes the human auditory system in a comprehensive
      fashion, strengthening neurobiological and cognitive underpinnings of both music
      and speech processing. In this review we argue not only that common neural
      mechanisms for speech and music exist, but that experience in music leads to
      enhancements in sensory and cognitive contributors to speech processing. Of
      specific interest is the potential for music training to bolster neural
      mechanisms that undergird language-related skills, such as reading and hearing
      speech in background noise, which are critical to academic progress, emotional
      health, and vocational success.

PMID- 22993459
TI  - Light through the dark ages: The Arabist contribution to Western ophthalmology.
AB  - Europe in the Middle Ages had descended into a dark period, and none more so than
      in the field of medicine. The rich heritage of the pagan Greeks had largely been
      ignored or forgotten by medieval Europe, and instead it was the early Arabist
      world that embraced and developed the Hellenistic medical teachings, emerging not
      only as guardians of the classical learning still existent, but also as pioneers
      and innovators, restricted only by the development in the associated fields. The
      Kahhal (), or Oculist or Eye Specialist, had a privileged place in royal
      households, especially during the Abbasid period, in contrast to the time of
      Galen, whose writings referred to ophthalmologists in a rather derogatory manner.
      This elevated standing in the medical profession allowed Arabist scholars to
      cultivate remarkably erudite techniques and exceptional texts, which were used
      until very recently.

PMID- 22993460
TI  - Short-term results of intravitreal dexamethasone implant (OZURDEX((r))) in
      treatment of recalcitrant diabetic macular edema: A case series.
AB  - CONTEXT: Dexamethasone Posterior-Segment Drug Delivery System is a novel,
      biodegradable, sustained-release drug delivery system (OZURDEX((r))) for
      treatment of macular edema following retinal vein occlusion and posterior
      uveitis. However, its potential role in management of diabetic macular edema has
      not been reported yet. AIM: The aim was to evaluate the safety and efficacy of
      (OZURDEX((r))) in patients with recalcitrant diabetic macular edema (DME).
      SETTING AND DESIGN: A retrospective, interventional case series from a tertiary
      eye care center in India is presented. Inclusion criteria comprised patients
      presenting with recalcitrant DME, 3 or more months after one or more treatments
      of macular laser photocoagulation and/or intravitreal anti-vascular endothelial
      growth factor (VEGF) injections. Exclusion criteria included history of
      corticosteroid-responsive intraocular pressure (IOP) rise, cataract extraction,
      or other intraocular surgery within 3 months. The main outcome measure was visual
      acuity at 1 and 4 months after OZURDEX((r)) injection. Secondary outcome measures
      included change in central macular thickness on Optical coherence tomography
      (OCT) and changes in IOP following intravitreal OZURDEX((r)) implant. Of 18 eyes
      (17 patients) with recalcitrant diabetic macular edema that underwent
      OZURDEX((r)) implant, three eyes (two patients) had follow-up of more than 3
      months post-injection. RESULTS: Mean age of patients was 56 years. Mean duration
      of diabetes mellitus was 16.6 years. Systemic control of DM was good as assessed
      by FBS/PPBS and HbA1c. The pre-operative mean central macular thickness was 744.3
      MUm and improved to 144 and 570 MUm at months 1 and 4, respectively. Preoperative
      mean BCVA was 0.6 logMAR units and improved to 0.3 and 0.46 logMAR units at month
      1 and 4, respectively. The mean follow-up was 4.3 months (range 4-5 months).
      CONCLUSION: OZURDEX((r)) appears efficacious in management of recalcitrant
      diabetic macular edema. The results of the ongoing POSURDEX((r)) study will
      elaborate these effects better.

PMID- 22993461
TI  - Phacoemulsification in cases of pseudoexfoliation using in situ nuclear
      disassembly without nuclear rotation.
AB  - PURPOSE: The purpose was to assess the safety and frequency of intraoperative
      complications of phacoemulsification using an in situ nuclear disassembly
      technique in pseudoexfoliation (PEX) cases. SETTING: The work was done in Rustaq
      Hospital, Rustaq, Sultanate of Oman. MATERIALS AND METHODS: This prospective,
      interventional, noncomparative study included 103 cases of cataract with
      pseudoexfoliation that underwent phacoemulsification with in situ nuclear
      disassembly using Alcon Infinity machine with Ozil handpeice and Kelman-style 45
      degrees  phacoemulsification tip. RESULTS: Of the 103 cases, 55 males (53.4%) and
      48 (46.6%) females, one case developed posterior capsular rupture, and four cases
      developed zonular dehiscence that was partial in three cases and >180 degrees  in
      one case only. The best corrected visual acuity (BCVA) 4 weeks postoperatively
      using logMAR notation was as follows: 66 cases (65.1%) had BCVA of 0.30 or better
      (logMAR notation), and 37 cases (35.9%) had BCVA of 0.48 or less. CONCLUSION:
      Safe and efficient phacoemulsification without nuclear rotation could be achieved
      in cases pseudoexfoliation in which zonular weakness is a concern by utilizing
      the versatility of Kelman style phaco tip to do lateral sweep sculpting and in
      situ cracking techniques. It prevents zonular stress by avoiding manipulation or
      rotation of the nucleus in cases.

PMID- 22993462
TI  - Reliability of a modified logMAR distant visual acuity chart for routine clinical
      use.
AB  - BACKGROUND/AIM: Acuity charts that follow the principle of logarithmic size
      progression (logMAR charts) are considered to be the gold standard for the
      assessment of distant vision. But it is not well accepted for routine eye
      examinations due to increased testing time and the complexity of scoring. This
      study was designed to check whether a modified logMAR chart with three optotypes
      would provide a reliable acuity assessment compared to standard logMAR charts for
      routine eye examination. MATERIALS AND METHODS: Two versions of modified and
      standard logMAR charts were designed, constructed, and used to assess the visual
      acuity of 50 individuals drawn from a typical out-patient population. Timed test
      retest variability and limit of agreement (95% confidence limit of agreement) of
      the modified chart are compared to the standard logMAR chart using Bland-Altman
      method. A comparison of the testing time was carried out using paired t-test.
      RESULTS: The test-retest variability of the charts was comparable, with 95%
      confidence limit of the mean difference being +/-0.08 for standard logMAR and +/
      0.10 for modified logMAR. Both the versions of modified logMAR charts produced
      the results which agreed well with those of the standard logMAR charts. The mean
      testing time required to complete the acuity measurements with the modified chart
      was significantly lesser compared to the standard chart (P < 0.001). CONCLUSION:
      The outcomes of the current study demonstrates that the modified logMAR chart
      with three optotypes offers a comparable result to the standard logMAR charts for
      assessing distant visual acuity in routine clinical examination set up with a
      much lesser testing time.

PMID- 22993463
TI  - Prevalence of myopia and its association with diabetic retinopathy in subjects
      with type II diabetes mellitus: A population-based study.
AB  - OBJECTIVE: To report the prevalence of myopia and its association with diabetic
      retinopathy in subjects with type II diabetes mellitus and compare the diabetic
      retinopathy status in the myopic group vs the emmetropic group. DESIGN:
      Population-based study. MATERIALS AND METHODS: The population-based study
      estimated the prevalence of myopia from 1058 subjects, who were more than 40
      years old and had type II diabetes mellitus; the patients were enrolled from a
      cross-sectional study. Participants answered a detailed questionnaire and
      underwent biochemical, physical and comprehensive ocular examination which
      included grading of nuclear sclerosis by lens opacities classification system III
      (LOCS III), seven field fundus photography and ultrasonography. Diabetic
      retinopathy and diabetic maculopathy were graded using the Klein's classification
      and early treatment diabetic retinopathy study (ETDRS) criteria respectively.
      RESULTS: The prevalence of mild, moderate and high myopia in type 2 diabetes was
      15.9, 2.1 and 1.9% respectively. The prevalence of any myopia was found to be
      19.9% in our study population. After adjusting the age, gender, duration of
      diabetes, hemoglobin A1c and other factors, increasing age was associated with
      mild and moderate myopia [OR 1.11 (95% CI 1.05 - 1.18)]. Compared to emmetropia,
      complete posterior vitreous detachment (CPVD) was associated with high myopia
      (50% Vs 12.2%, P < 0.0001). Myopia had no association with diabetic retinopathy.
      CONCLUSION: The prevalence of myopia and high myopia was found to be 19.9 and
      1.9% respectively among subjects with type II diabetes. Myopia was not associated
      with diabetic retinopathy, thereby, suggesting the need for a longitudinal study.

PMID- 22993464
TI  - Comparison between Humphrey Field Analyzer and Micro Perimeter 1 in normal and
      glaucoma subjects.
AB  - PURPOSE: To determine the correlation between fundus perimetry with Micro
      Perimeter 1 (MP1) and conventional automated static threshold perimetry using the
      Humphrey Field Analyzer (HFA) in healthy individuals and in subjects with
      glaucoma. MATERIALS AND METHODS: In this study, we enrolled 45 eyes with glaucoma
      and 21 eyes of age-matched, healthy individuals. All subjects underwent complete
      ophthalmic examination. Differential light sensitivity was measured at 21
      corresponding points in a rectangular test grid in both MP1 and HFA. Similar
      examination settings were used with Goldmann III stimulus, stimulus presentation
      time of 200 ms, and white background illumination (1.27 cd/m(2)). Statistical
      analysis was done with the SPSS 14 using linear regression and independent t
      test. RESULTS: The mean light thresholds of 21 matching points in control group
      with MP1 and HFA were 14.97 +/- 2.64 dB and 30.90 +/- 2.08 dB, respectively. In
      subjects with glaucoma, the mean values were MP1: 11.73 +/- 4.36 dB and HFA:
      27.96 +/- 5.41 dB. Mean difference of light thresholds among the two instruments
      was 15.86 +/- 3.25 dB in normal subjects (P < 0.001) and 16.22 +/- 2.77 dB in
      glaucoma subjects (P < 0.001). Pearson correlation analysis of the HFA and MP1
      results for each test point location in both cases and control subjects showed
      significant positive correlation (controls, r = 0.439, P = 0.047; glaucoma
      subjects, r = 0.812, P < 0.001). There was no difference between nasal and
      temporal points but a slight vertical asymmetry was observed with MP1.
      CONCLUSION: There are significant and reproducible differences in the
      differential light threshold in MP1 and HFA in both normal and glaucoma subjects.
      We found a correction factor of 17.271 for comparison of MP1 with HFA. MP1
      appeared to be more sensitive in predicting loss in glaucoma.

PMID- 22993465
TI  - Varied aetiology of acute acquired comitant esotropia: A case series.
AB  - This is an observational case series of five cases of acute acquired comitant
      esotropia (AACE) with diplopia, aged between 5 and 12 years. The duration of
      presenting complaints ranged from 4 days to 2 months. A detailed ophthalmic
      evaluation and neuroimaging were done on all patients. Three patients were found
      to have intracranial pathology. Two patients had pontine glioma and one patient
      had benign intracranial hypertension. One patient was diagnosed as accommodative
      spasm and one patient was diagnosed as having Type 2 AACE.We would like to
      conclude that AACE can be of a varied aetiology ranging from convergence spasm to
      those harboring serious intracranial diseases. We reiterate that AACE has a small
      but significant association with intracranial disorders. Neuroimaging is a
      definite need in cases which cannot be proved to be either Type 1 or 2.

PMID- 22993466
TI  - Bilateral symmetrical corneal melting following intravesical Bacille Calmette
      Guerin therapy for bladder carcinoma.
AB  - A 63-year-old man with unremarkable previous ocular history presented with
      bilateral symmetrical corneal ulceration along with mucopurulent conjunctivitis
      and dry eye 10 days after the fourth dose of intravesical Bacille Calmette-Guerin
      (BCG) instillation for treatment of bladder carcinoma. Slit lamp examination
      revealed thinning of the cornea at the base of the ulcer in both eyes.
      Conjunctival swab and scraping from ulcer sent for Gram and acid fast bacilli
      stain and culture were negative. On the basis of history, clinical examination,
      and laboratory investigations, we diagnosed it as bilateral immune mediated
      sterile corneal ulceration along with mucopurulent conjunctivitis and dry eye. He
      was treated with topical antibiotics, cycloplegics, cyclosporine, lubricant gel,
      and bandage contact lens. There was progressive stromal melting, descemetocele
      formation, and perforation in the inferior part of cornea in both the eyes. He
      was treated with pulse steroid and paramedian tarsorraphy in both eyes. The
      patient was subsequently lost to follow-up. We report this case to highlight this
      rare complication of BCG therapy, in order to improve their management protocol
      in patients with similar clinical profile. We could not find a similar case after
      thorough PubMed search.

PMID- 22993467
TI  - Diplopia as the primary presentation of foodborne botulism.
AB  - Foodborne botulism is a serious condition caused by Clostridium botulinum
      neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy
      and descending paralysis. We report a unique presentation of botulism to remind
      clinicians of this potentially fatal condition. In this observational case report
      initial evaluation showed only esodeviation. This progressed to unilateral
      cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis
      was made based on in-depth history and concurrent symptoms in three other
      patients. Foodborne botulism presenting as diplopia and unilateral motility
      deficits is rare and can represent a diagnostic and therapeutic challenge to the
      ophthalmologist.

PMID- 22993468
TI  - Spontaneous resolution of double anterior chamber with perforation of Descemet's
      membrane in deep anterior lamellar keratoplasty.
AB  - Deep anterior lamellar keratoplasty (DALK) using Dr. Anwar's big bubble technique
      was performed for a patient with granular dystrophy. Intraoperatively, a
      perforation of the Descemet's membrane (DM) was noted inferonasally. Though the
      surgery was completed, the donor graft appeared to have an intact endothelium,
      which was inadvertently left behind by the surgeon. Intraoperatively, there was a
      perforation of inferonasal DM and surgery was completed by inadvertently placing
      a donor with an intact endothelium. Postoperatively the patient presented with a
      complete DM detachment and a resultant double anterior chamber (DAC). In spite of
      two attempts at an air tamponade on the first and fifth post operative days, the
      DAC still persisted. Surprisingly, during the 6(th) week follow up visit, there
      was a complete resolution of the DAC as well as total recovery of vision. This
      interesting case clearly exemplifies that, in spite of failed attempts at air
      tamponade, a DM detachment and a DAC due to DM perforation following a DALK
      procedure can resolve spontaneously with good visual outcome.

PMID- 22993469
TI  - Kearns-Sayre syndrome: An unusual ophthalmic presentation.
AB  - Kearns-Sayre syndrome (KSS) belongs to the group of neuromuscular disorders known
      as mitochondrial encephalomyopathies. It has characteristic syndromal features,
      which include: chronic progressive external ophthalmoplegia, bilateral atypical
      pigmentary retinopathy, and cardiac conduction abnormalities. So far, only a
      single case has been reported where a patient with KSS had a normal retina.
      Herein, we report this extremely rare variant of KSS, which not only presented
      later than the normal age of presentation, but also had minimal pigmentary
      retinopathy.

PMID- 22993470
TI  - Orbital dermoid mimicking a monocular elevation deficiency.
AB  - Dermoid cysts are choristomas (a mass of histologically normal tissue in an
      abnormal location), which originate from aberrant primordial tissue and are often
      evident soon after birth. It may occur anywhere in the body. Dermoid cysts
      account for about 3-9% of all orbital masses and 0.04-0.6% of primary orbital
      tumors. The frequent site of origin is the superotemporal quadrant of orbit.
      Depending on the location, size, and associated abnormalities of the cyst, the
      patient may have proptosis, diplopia, and restriction of eye movements. Monocular
      elevation deficiency (MED) is the inability to elevate one eye in abduction,
      adduction, or from primary position. We report this case of orbital dermoid in an
      adult female presenting as a monocular elevation deficiency with unilateral
      ptosis of right eye which was investigated and managed with good results.

PMID- 22993471
TI  - Unilateral keratoconus presenting with acute hydrops in a patient with mental
      retardation, epilepsy, and bronchial asthma.

PMID- 22993472
TI  - Idiopathic orbital inflammatory disease.

PMID- 22993473
TI  - An unusual pattern of idiopathic choroidal folds.

PMID- 22993474
TI  - Childhood proptosis: Relevance of aspiration cytology in the era of newer
      molecular diagnostic and imaging techniques.

PMID- 22993475
TI  - Anterior segment optical coherence tomography in intracorneal foreign body.

PMID- 22993476
TI  - Recurrent bilateral subconjunctival hemorrhage as an initial presentation of
      multiple myeloma.

PMID- 22993477
TI  - Bilateral, symmetrical zygomatic mass.

PMID- 22993478
TI  - An immunohistochemical analysis of P-glycoprotein in retinoblastoma.

PMID- 22993479
TI  - The effect of gender on pain experienced during cataract surgery.

PMID- 22993480
TI  - Authors' reply.

PMID- 22993481
TI  - Diabetic papillopathy with macular edema treated with intravitreal bevacizumab.

PMID- 22993482
TI  - The Effectiveness of Mindfulness Training on Behavioral Problems and Attentional
      Functioning in Adolescents with ADHD.
AB  - The effectiveness of an 8-week mindfulness training for adolescents aged 11-15
      years with ADHD and parallel Mindful Parenting training for their parents was
      evaluated, using questionnaires as well as computerized attention tests.
      Adolescents (N = 10), their parents (N = 19) and tutors (N = 7) completed
      measurements before, immediately after, 8 weeks after and 16 weeks after
      training. Adolescents reported on their attention and behavioral problems and
      mindful awareness, and were administered two computerized sustained attention
      tasks. Parents as well as tutors reported on adolescents' attention and
      behavioral problems and executive functioning. Parents further reported on their
      own parenting, parenting stress and mindful awareness. Both the mindfulness
      training for the adolescents and their parents was delivered in group format.
      First, after mindfulness training, adolescents' attention and behavior problems
      reduced, while their executive functioning improved, as indicated by self-report
      measures as well as by father and teacher report. Second, improvements in
      adolescent' actual performance on attention tests were found after mindfulness
      training. Moreover, fathers, but not mothers, reported reduced parenting stress.
      Mothers reported reduced overreactive parenting, whereas fathers reported an
      increase. No effect on mindful awareness of adolescents or parents was found.
      Effects of mindfulness training became stronger at 8-week follow-up, but waned at
      16-week follow-up. Our study adds to the emerging body of evidence indicating
      that mindfulness training for adolescents with ADHD (and their parents) is an
      effective approach, but maintenance strategies need to be developed in order for
      this approach to be effective in the longer term.

PMID- 22993485
TI  - Roles of the university in disaster management.

PMID- 22993484
TI  - Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome
      proliferator-activated receptor-gamma2 gene and diabetic retinopathy in
      Caucasians and Asians.
AB  - PURPOSE: The Pro12Ala polymorphism of the peroxisome proliferator-activated
      receptor-gamma2 (PPARgamma2) gene is reported to be associated with diabetes.
      However, the gene's association with diabetic retinopathy (DR) in type 2 diabetes
      mellitus (T2DM) has been investigated in numerous epidemiologic studies with
      controversial results. This meta-analysis aimed to collectively assess the
      association of the Pro12Ala polymorphism with DR in T2DM. METHODS: An electronic
      literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the
      China National Knowledge Internet. A dominant model [(Pro/Ala +Ala/Ala) versus
      Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs)
      and 95% confidence intervals (CIs) were calculated using the fixed effect model.
      Potential sources of heterogeneity and bias were explored. RESULTS: This meta
      analysis included genotype data from 2,720 cases with DR and 2,450 controls free
      of DR from eight eligible publications. The results showed the Ala allele had a
      protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68-0.98, p=0.03). There was
      no significant evidence against homogeneity (I(2)=46%, P(heterogeneity)=0.07).
      The sensitivity analysis showed a robust association of the Pro12Ala polymorphism
      with DR in T2DM after a study involving Caucasians that presented a big effect on
      heterogeneity (OR=0.75; 95% CI: 0.62-0.91, p=0.003) was excluded. Possible ethnic
      differences in the association of the Pro12Ala single nucleotide polymorphism and
      DR were demonstrated; a significant association was illustrated in the Caucasian
      subgroup (OR=0.74; 95% CI: 0.59-0.94, p=0.01) but was not found in the Asian
      subgroup (OR=0.77; 95% CI: 0.55-1.07, p=0.12). No publication bias was observed.
      CONCLUSIONS: This meta-analysis suggested a significant association exists
      between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala
      allele had a significant protective effect against DR in T2DM.

PMID- 22993486
TI  - How to develop a core curriculum in clinical skills for undergraduate medical
      teaching in the school of medical sciences at universiti sains malaysia?
AB  - Clinical skills program as a laboratory method is a valuable adjunct to other
      forms of undergraduate medical training. This article describes the process of
      developing a core curriculum in clinical skills based on the Dundee model for a
      clinical skills centre. The School of Medical Sciences, in Universiti Sains
      Malaysia (USM) has been provided with a well equipped skills centre. However, the
      PBL curriculum in the undergraduate medical program in the school needs to be
      integrated with a clinical skills lab program. This is to counter the general
      feeling that the contribution of PBL is insignificant in terms of building
      clinical competency in an integrated system such as that used in USM compared to
      the traditional curriculi of other medical teaching institutions in Malaysia.
      Integrating clinical skills laboratory training with the PBL curriculum will
      provide evidence of PBL as an effective and innovative method for teaching and
      learning in Malaysia.

PMID- 22993483
TI  - Bilberries potentially alleviate stress-related retinal gene expression induced
      by a high-fat diet in mice.
AB  - PURPOSE: Obesity- and diabetes-associated visual impairment and vascular
      dysfunctions are increasing as causes of vision loss. The detailed mechanisms of
      how obesity and diabetes affect eye health are still largely unknown, but animal
      models have been useful in exploring the effects of potential protective
      compounds, i.e., compounds characterized by antioxidant and anti-inflammatory
      properties. These properties occur in anthocyanins, and bilberries (European wild
      blueberries, Vaccinium myrtillus) are a major source of dietary anthocyanins in
      Nordic diets. The main aim of the present work was to study the protective
      effects of dietary bilberries (BB) on the level of gene expression in retinas in
      mice that develop obesity when fed a high-fat diet (HFD). METHODS: Mice (n=6 per
      group, four groups) were fed ad libitum a normal control diet (NCD), a HFD, or a
      diet with 5% bilberries (NCD+BB, HFD+BB) for 12 weeks. Food consumption, weight
      gain, and blood pressure were measured during the feeding period and whole blood
      serum markers of obesity at sacrifice. Retinas were collected, and RNA extracted
      from all 24 mice and pooled samples from four mice per group were hybridized to
      Mouse-Ref8 V2 Expression BeadChips (Illumina platform) with 25,697 probes for
      genes and transcript variants. The expression profiles in the retinas were
      analyzed using R, PathVisio, and DAVID to screen for high fat-induced changes as
      well as for bilberry-induced changes in the HFD up- or downregulated transcripts.
      RESULTS: The HFD and HFD+BB groups gained weight from week 5 and final weight,
      blood glucose, serum free fatty acids, and systolic blood pressure as compared to
      mice fed the control diets (Mann-Whitney's U-test, p<0.05). Bilberries had no
      significant effect on these parameters other than a trend to reduce systolic
      blood pressure in the HFD-fed mice (101+/-4 versus 113+/-9 mmHg, p=0.10). Gene
      ontology enrichment analysis of 810 differentially expressed genes (F-test,
      p<0.05) in the retina displayed differential regulation of genes in ontology
      groups, mainly pathways for apoptosis, inflammation, and oxidative stress,
      especially systemic lupus erythematosus, mitogen-activated protein kinase, and
      glutathione metabolism. Mice fed a HFD had increased retinal gene expression of
      several crystallins, while the HFD+BB mice showed potential downregulation of
      these crystallins when compared to the HFD mice. Bilberries also reduced the
      expression of genes in the mitogen-activated protein kinase (MAPK) pathway and
      increased those in the glutathione metabolism pathway. CONCLUSIONS: HFD feeding
      induces differential expression of several stress-related genes in the mouse
      retina. Despite minor effects in the phenotype, a diet rich in bilberries
      mitigates the upregulation of crystallins otherwise induced by HFD. Thus, the
      early stages of obesity-associated and stress-related gene expression changes in
      the retina may be prevented with bilberries in the diet.

PMID- 22993487
TI  - The routine histopathological examination of tonsillectomy specimens at hospital
      universiti sains malaysia - 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 specimens post-tonsillectomy. In this
      paper, a retrospective evaluation of 480 specimens from 241 patient who has
      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 malignant. The result of this study indicate that routine
      histopathological examination of tonsillectomy specimens are unnecessary and
      results only in added cost and a loss of man hours.

PMID- 22993488
TI  - Clinical and audiological profiles in children with chronic otitis media with
      effusion requiring surgical intervention.
AB  - To determine the characteristic presenting symptoms, otoscopic findings,
      audiological profiles and the intraoperative findings of children with chronic
      otitis media with effusion who required surgical intervention. A prospective
      cross sectional study was undertaken in the otorhinolaryngology clinic of USM
      Hospital (HUSM) involving 25 cases (50 ears) of children with chronic otitis
      media with effusion requiring surgical intervention from June 1999 to September
      2001. Their ages ranged from 3 to 12 years old. The gender distribution included
      males at 72 % and females at 28 %. The presenting symptoms noted were hearing
      impairment (52%), otalgia (18%), ear block (16%) and tinnitus (14%). The
      otoscopic findings were fluid in the middle ear (40%), dullness (32%) and
      retraction of the tympanic membrane (28%). On audiometry, 24 ears had moderate
      deafness (48%), 16 ears had mild deafness (32%) while 4 ears had severe deafness
      (8%). With tympanometry, 42 ears out of the total 50 had a flat type B curve
      (84%) while 6 ears had type As curve (12%). During myringotomy, middle ear
      secretion was seen in 38 ears (76%) out of the 50 ears; 22 ears had mucoid
      secretion while 16 ears had serous secretion. Clinically, the commonest
      presenting symptom was hearing impairment (52%) while the most common otoscopic
      finding was fluid in the middle ear (40%). Audiologically, most patients had
      moderate conductive hearing loss (48%) and a type B curve (84%) on tympanometry.
      On myringotomy middle ear fluid was found in 76 % of the ears.

PMID- 22993489
TI  - Hospital Outcomes of Adult Respiratory Tract Infections with Extended-Spectrum B
      Lactamase (ESBL) Producing Klebsiella Pneumoniae.
AB  - Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring
      hospitalization in Malaysia. To study whether extended-spectrum b-lactamase
      (ESBL) producing K. pneumoniae was linked to hospital outcomes, we
      retrospectively studied 441 cases of adult respiratory tract infections with
      microbial proven K. pneumoniae from an urban-based university teaching hospital
      between 2003 and 2004. 47 (10.6%) cases had ESBL. Requirement for ventilation and
      median length of hospital stay, were greater in 'ESBL' than in 'non-ESBL' group
      [34% vs. 7.4%, p<0.001; 14 days vs. 5 days, p<0.001 respectively] but not crude
      hospital mortality rate [21.3% vs. 12.4%, p=0.092]. There was a four-fold
      increased risk of requiring ventilation [4.61 (2.72-7.85)] when ESBL was present.
      Our findings support the association of ESBL producing K. pneumoniae with
      adversed hospital outcomes and reiterate the need for vigilance on the part of
      treating clinicians.

PMID- 22993490
TI  - Evaluation of anaesthesia methods in caesarean section for foetal distress.
AB  - The purpose of this study was to evaluate the anaesthetic technique for Caesarean
      section which was appropriate for the clinical situation. This retrospective
      study was conducted on 240 patients undergoing Caesarean section with indications
      of foetal distress during a 3-year period (2002-2004). The data were reviewed
      from the patient's medical record of the Department of Anesthesiology, Dr Soetomo
      Hospital, Surabaya. The patients were divided into three groups, according to the
      criteria of foetal heart rates. The success of the anaesthesia methods was
      determined by assessing the Apgar scores of the newborn baby. The results were
      analyse using Kruskal-Wallis and Chi-Square test. P <=0.05 was considered as
      statistically significant. 1- and 5-minute Apgar score of the normal range group
      was significantly higher than that of the bradycardia group (p<0.05), but no
      significant differences was found between the normal range and the tachycardia
      group (p>0.05). One- and five- minute Apgar scores of the sub-arachnoid block
      group were significantly higher than those of the general anesthesia group
      (p<0.05). One-minute Apgar score of the ketamine group was significantly higher
      than that of the thiopental group (p<0.05), but no significant differences in 5
      minute Apgar score was found between the ketamine and the thiopental groups
      (p>0.05). We conclude that subarachnoid block is the choice of anaesthesia for
      patients undergoing Caesarean section for foetal distress's diagnosed at PS 1 and
      2 patients. General anaesthesia with ketamine Apgar score at one minute better
      than that of the thiopental.

PMID- 22993491
TI  - Alpha lipoic Acid prevents pancreatic islet cells damage and dyslipidemia in
      streptozotocin-induced diabetic rats.
AB  - In the present study, the effects of alpha lipoic acid (ALA) supplementation on
      glycemic control and lipid profile in streptozotocin (STZ)-induced diabetic rats
      have been evaluated. Sprague Dawley rats were divided into nondiabetic (NDM),
      diabetic without supplementation (No Suppl) and diabetic with ALA groups. ALA was
      orally administered once a day for 8 weeks with a dose of 100 mg/kg BW.
      Supplementation of ALA to STZ-induced rats prevented the severe damage to the
      islet cells of the pancreas and lowered the plasma glucose and glycated
      hemoglobin (HbA1c) levels. Supplementation of ALA also suppressed the increased
      of total cholesterol (TC), triglycerides and low density lipoprotein-cholesterol
      (LDL-C) levels in the plasma of diabetic rats as well as increased high density
      lipoproteincholesterol (HDL-C) levels. In conclusion, this study suggest that ALA
      may be effective in controlling glycemic status and improving dyslipidemia in
      streptozotocin-induced diabetic rats and has the potential in reducing
      cardiovascular complications due to diabetes mellitus.

PMID- 22993492
TI  - Hereditary spherocytosis in a malay patient with chronic haemolysis.
AB  - This case report describes a 35-year-old lady who presented with generalized
      weakness and lethargy of two weeks duration and jaundice of more than 20 years
      duration. Her initial workup was suggestive of haemolysis and blood film showed a
      leucoerythoblastic picture with moderate microspherocytes. She was finally
      diagnosed as a case of hereditary spherocytosis after ruling out other possible
      causes of chronic haemolysis and supported by an abnormal osmotic fragility test,
      although family members refused for screening. Hereditory spherocytosis is
      uncommon in Malay population and presentation with jaundice of 20 years duration
      with leucoerythroblastic picture on blood film were interesting features in this
      case. Patient is being followed closely for need of splenectomy in near future as
      per severity of haemolysis and currently being managed with folic acid
      supplement.

PMID- 22993493
TI  - Hand grenade blast injuries: an experience in hospital universiti sains malaysia.
AB  - Hand grenade explosion is a rare occasion in our local community. Most of us have
      seen or heard about the injuries only from the TV news or newspaper. We report
      two cases of bomb blast injury that occurred in an army camp in September 2000.
      These case studies illustrate the clinical presentations of hand grenade blast
      injures that present with multiple organ involvement. We would like to share our
      experience in managing such cases in a busy emergency department and highlight
      the outcome of those two cases. Certain issues pertaining to the complexity of
      the injuries and mass casualty management are also highlighted.

PMID- 22993494
TI  - Dental infection presenting with ipsilateral parapharyngeal abscess and
      contralateral orbital cellulitis - a case report.
AB  - A 43 year-old man presented with pain on the right tooth for three days duration.
      Computed tomography showed left orbital cellulitis and right parapharyngeal
      abscess. There was also evidence suggestive of a dental abscess over right upper
      alveolar region. Magnetic resonance imaging revealed left superior ophthalmic
      vein thrombosis. Emergency drainage of the right parapharyngeal abscess was
      performed. Right maxillary molar extraction revealed periapical abscess. Left eye
      proptosis markedly reduced after initiating heparin.

PMID- 22993495
TI  - A Survey on Lower Urinary Tract Symptoms (LUTS) Among patients with Benign
      Prostatic Hyperplasia (BPH) in Hospital Universiti Sains Malaysia (HUSM).
AB  - Patients with Benign Prostatic Hyperplasia (BPH) commonly presents with lower
      urinary tract symptoms (LUTS), which can be of obstructive symptoms such as
      hesitancy, incomplete voiding, post void dribbling or of irritative symptoms such
      as urgency, frequency and nocturia. Various recent studies indicate that nocturia
      is a very important and bothersome lower urinary tract symptom especially among
      patients with Benign Prostatic Hyperplasia (BPH). The aims of the study was to
      determine the frequency of common urinary symptoms among patients with BPH in
      HUSM as well as to evaluate the extent of bothersomeness of each and every
      symptom to these patients. This study too was aimed at evaluating the success of
      TURP in resolving pre operative LUTS. This was a questionnaire-based survey using
      a validated ICSBPH model whereby patients with BPH were selected and quizzed
      personally by an investigator. A subset of patients who had undergone TURP were
      further questioned regarding their satisfaction with the procedure. When nocturia
      is defined as waking up at night once or more to pass urine, the prevalence of
      nocturia was about 90%, but only 1 in 6 patients considered this is a very
      serious symptom. Even if the definition was changed to waking up twice or more,
      the prevalence is still quite high at over 80%. Urgency were noted in half of the
      patients, but only a quarter of them consider it a serious problem. 1 in 5
      patients experienced significant leak and almost all consider it serious. About
      one third of the studied population had to be catheterized due to urinary
      obstruction and interestingly only about half of them considered it as a very
      serious event. Overall, a great majority of these patients considered suffering
      from these urinary symptoms for the rest of their life as very devastating. This
      study conclude that although the prevalence of nocturia was high among BPH
      patients, but it was not considered serious by majority of them. In fact, LUTS in
      our BPH patients did not differ much from BPH patients elsewhere. On the whole,
      TURP resolved most of the LUTS effectively.

PMID- 22993496
TI  - Heart failure special edition.

PMID- 22993497
TI  - Triangulating Clinically Meaningful Change in the Six-minute Walk Test in
      Individuals with Chronic Heart Failure: A Systematic Review.
AB  - PURPOSE: The purpose of the present review was to use existing, published data to
      provide an estimate of the amount of change in six-minute walk test distance
      (Delta6MWT) that represents a clinically meaningful change in individuals with
      chronic heart failure (CHF). METHODS: THE PRESENT REVIEW INCLUDED TWO SEPARATE
      LITERATURE SEARCHES OF THE CINAHL AND MEDLINE DATABASES FOR ARTICLES THAT: (1)
      reported the intraclass correlation coefficient (ICC) of the 6MWT in individuals
      with CHF, and (2) used the 6MWT along with either aerobic capacity or health
      related quality of life (HRQL) as study endpoints in randomized controlled trials
      (RCTs) of exercise-based intervention for individuals with CHF. The ICCs were
      used to calculate the minimum detectable difference (MDD) at the 95% confidence
      interval for each included study. The Delta6MWT associated with aerobic capacity
      and HRQL within-group effect sizes for the intervention and control groups in
      each included RCT was analyzed using receiver operating characteristic (ROC)
      curves. RESULTS: Thirteen articles reported the ICC for the 6MWT. The mean
      (standard deviation) MDD calculated based on these data was 43.1(16.8) m.
      Eighteen RCTs measured the 6MWT and either aerobic capacity and/or HRQL. A
      Delta6MWT of 40-45 m was associated with at least moderate aerobic capacity and
      HRQL effect sizes in the intervention groups. The Delta6MWT thresholds that
      discriminated between intervention and control groups using ROC curves revealed
      the following sensitivity/specificity for the respective thresholds: 19 m,
      94.4/83.3%, 32 m, 83.3/94.4%, and 48 m 44.4/100% (AUC = .935, p = .009, CI(95%)
      .855, 1.015). CONCLUSIONS: A Delta6MWT of approximately 45 m appears to exceed
      measurement error and be associated with significant changes in either aerobic
      capacity and/or HRQL.

PMID- 22993498
TI  - Development and safety of an exercise testing protocol for patients with an
      implanted cardioverter defibrillator for primary or secondary indication.
AB  - PURPOSE: Performing exercise tests in patients with an implantable cardioverter
      defibrillator (ICD) presents specific challenges because of susceptibility to
      ventricular arrhythmias during maximal levels of exertion. The purpose of this
      paper is to outline the exercise testing protocol from the Anti-Arrhythmic
      Effects of Exercise after an ICD trial and to report baseline test results and
      safety outcomes using the protocol. METHODS AND RESULTS: Maximal cardiopulmonary
      exercise testing was performed to assess levels of physical fitness as part of a
      randomized trial of walking exercise in patients with ICDs. Subjects were
      randomized after baseline testing to aerobic exercise plus usual care or usual
      care alone. A modified Balke treadmill exercise test was used and specific ICD
      programming procedures were implemented to avoid unnecessary shocks, which
      included programming off ventricular tachycardia (VT) therapies during testing.
      To date, 161 baseline tests have been performed. One ventricular fibrillation
      (VF) cardiac arrest occurred following completion of an exercise test and three
      tests were stopped by the investigators due to nonsustained ventricular
      tachycardia. Eleven subjects were not able to achieve maximum exercise, defined
      as reaching an anaerobic threshold (AT) at baseline testing. There have been no
      deaths as a result of exercise testing. CONCLUSIONS: Symptom-limited maximal
      exercise testing can be performed safely and effectively in patients with ICDs
      for both primary and secondary prevention indications. Specific strategies for
      ICD programming and preparation for treating ventricular arrhythmias needs to be
      in place before exercise testing is performed.

PMID- 22993499
TI  - Exercise rehabilitation for chronic heart failure patients with cardiac device
      implants.
AB  - In the past decade a significant development in the management and rehabilitation
      of people with chronic heart failure (CHF) has been the utilization of cardiac
      devices. The use of biventricular pacemakers, referred to as Cardiac
      Resynchronization Therapy (CRT) can yield improvements in functional abilities
      for a select group of CHF patients and the inclusion of implantable cardiac
      defibrillators (ICDs) may reduce the risk of sudden death. This review provides
      physical therapists with a basic understanding of how to prescribe exercise for
      people with CHF who have these device implants.

PMID- 22993500
TI  - Inspiratory muscle training in patients with heart failure: a systematic review.
AB  - PURPOSE: The purpose of this review was to assess the quality of evidence on
      inspiratory muscle training (IMT) in patients with heart failure and to provide
      an overview on subject selection, training protocols, and outcome achieved with
      IMT. METHODS: Literature search was first performed via the PubMed database, and
      additional references were identified from the Scopus citation index. Articles of
      the review type and of clinical trials published in English were included.
      Quality of the articles was assessed using Sackett's levels of evidence and rigor
      of methodology was assessed using PEDro (Physiotherapy Evidence Database)
      criteria for randomized controlled trials and the Downs & Black tool for cohort
      studies. RESULTS: Twelve articles of clinical trials were included. Typical
      training protocols involved daily training with intensity greater than 30% of
      maximal inspiratory pressure (PImax), duration of 20 to 30 minutes (continuous or
      incremental) and using a pressure threshold muscle trainer. The effect sizes of
      PImax, walk test distance, and dyspnea were moderate to large across these
      studies. Effects on quality of life scores were inconsistent. CONCLUSION:
      Inspiratory muscle training is beneficial for improving respiratory muscle
      strength, functional capacity, and dyspnea in patients with stable heart failure
      and respiratory muscle weakness.

PMID- 22993501
TI  - Physical therapy management of two patients with stage d heart failure in the
      cardiac medical intensive care unit.
AB  - BACKGROUND AND PURPOSE: Due to the increasing prevalence of heart failure (HF)
      and medical advances extending the life expectancy of patients with HF, physical
      therapists are often consulted to assist in the management of these patients in
      light of the benefits of exercise for them. The purpose of this paper is to
      review the equipment and measures often encountered in patients with Stage D HF
      in the intensive care unit (ICU) and to discuss the care provided to two patients
      in this setting. CASE DESCRIPTIONS: One patient was a 40-year-old man with Stage
      D HF on multiple inotropes receiving physical therapy intervention while awaiting
      a cardiac transplant. The second patient was a 57-year-old man with Stage D HF
      due to ischemic cardiomyopathy, treated by physical therapy while receiving
      inotropic and intra-aortic balloon pump support, awaiting a renal and cardiac
      transplant. DISCUSSION: Different physical therapy interventions were safely
      provided to both patients during their cardiac medical ICU courses. Despite
      multiple medical issues requiring more complex decision making skills, this
      patient population may greatly benefit from physical therapy intervention.

PMID- 22993502
TI  - Program description: physical therapy in a heart failure clinic.
AB  - Aerobic exercise and resistance training have been proven to be beneficial for
      patients with heart failure. Current reimbursement guidelines exclude these
      patients from our traditional cardiac rehabilitation program, so at Newton
      Wellesley Hospital a clinic model was developed for the disease management and
      exercise of heart failure patients.

PMID- 22993504
TI  - Methods for the Study of Development - Developing Methods: Introduction to a
      Special Issue of Research in Human Development.
AB  - This collection of articles explores how contemporary methods interface with and
      can be used effectively to test developmental perspectives and hypotheses. The
      authors review some of the latest advancements in measurement and scale equating,
      multilevel models of change, growth mixture models, longitudinal models of
      mediation, and survival models and illustrate how these methods can be applied to
      developmental data. In this introduction, we present the data-box as a useful
      heuristic for both assessing the conceptual assumptions and implications of a
      given research approach and selecting the appropriately aligned statistical
      models for measurement, change, and interindividual differences. Together, the
      articles provide accessible introductions, illustrations, and discussions of how
      some of the recent methodological innovations might be applied in the study of
      development.

PMID- 22993505
TI  - The human brain intracerebral microvascular system: development and structure.
AB  - The capillary from the meningeal inner pial lamella play a crucial role in the
      development and structural organization of the cerebral cortex extrinsic and
      intrinsic microvascular compartments. Only pial capillaries are capable of
      perforating through the cortex external glial limiting membrane (EGLM) to enter
      into the nervous tissue, although incapable of perforating the membrane to exit
      the brain. Circulatory dynamics and functional demands determine which
      capillaries become arterial and which capillaries become venous. The perforation
      of the cortex EGLM by pial capillaries is a complex process characterized by
      three fundamental stages: (1) pial capillary contact with the EGLM with fusion of
      vascular and glial basal laminae at the contact site, (2) endothelial cell
      filopodium penetration through the fussed laminae with the formation of a funnel
      between them that accompanies it into the nervous tissue while remaining open to
      the meningeal interstitium and, (3) penetration of the whole capillary carrying
      the open funnel with it and establishing an extravascular Virchow-Robin
      Compartment (V-RC) that maintains the perforating vessel extrinsic (outside) the
      nervous tissue through its entire length. The V-RC is walled internally by the
      vascular basal lamina and externally by the basal lamina of joined glial cells
      endfeet. The VRC outer glial wall appear as an extension of the cortex
      superficial EGLM. All the perforating vessels within the V-RCs constitute the
      cerebral cortex extrinsic microvascular compartment. These perforating vessels
      are the only one capable of responding to inflammatory insults. The V-RC remains
      open (for life) to the meningeal interstitium permitting the exchanges of fluid
      and of cells between brain and meninges. The V-RC function as the brain sole
      drainage (prelymphatic) system in both physiological as well as pathological
      situations. During cortical development, capillaries emerge from the perforating
      vessels, by endothelial cells growing sprouts analogous to their angiogenesis,
      entering into their corresponding V-RCs. These new capillaries to enter into the
      nervous tissue must perforate through the V-RC outer glial wall, a process
      analogous to the original perforation of the cortex EGLM by pial capillaries.
      These emerging capillaries are incapable of reentering the V-RCs and/or
      perforating vessels. As the new capillary enters into the nervous tissue, it
      becomes surrounded by glial endfeet and carries a single basal lamina (possibly
      glial). Capillaries emerging from contiguous perforators establish an anastomotic
      plexus between them, by mechanisms still poorly understood. The capillaries of
      this anastomotic plexus constitute the cerebral cortex intrinsic microvascular
      compartment and together constitute the so-called blood-brain-barrier. The
      intrinsic capillaries are changing and readapting continuously, by both active
      angiogenesis and reabsorption, to the gray matter neurons developmental and
      functional needs. The brain intrinsic capillaries are among the most active
      microvessels of the human body. Unresolved developmental and functional aspects
      concerning the cerebral cortex intrinsic capillary plexus need to be further
      investigated.

PMID- 22993506
TI  - Remote spatial memory in aging: all is not lost.
AB  - The ability to acquire and retain spatial memories in order to navigate in new
      environments is known to decline with age, but little is known about the effect
      of aging on representations of environments learned long ago, in the remote past.
      To investigate the status of remote spatial memory in old age, we tested healthy
      young and older adults on a variety of mental navigation tests based on a large
      scale city environment that was very familiar to participants but rarely visited
      by the older adults in recent years. We show that whereas performance on a route
      learning test of new spatial learning was significantly worse in older than
      younger adults, performance was comparable or better in the older adults on
      mental navigation tests based on a well-known environment learned long ago. An
      exception was in the older adults' ability to vividly re-experience the well
      known environment, and recognize and represent the visual details contained
      within it. The results are seen as analogous to the pattern of better semantic
      than episodic memory that has been found to accompany healthy aging.

PMID- 22993507
TI  - Voltage-Controlled Enzymes: The New JanusBifrons.
AB  - The Ciona intestinalis voltage-sensitive phosphatase, Ci-VSP, was the first
      Voltage-controlled Enzyme (VEnz) proven to be under direct command of the
      membrane potential. The discovery of Ci-VSP conjugated voltage sensitivity and
      enzymatic activity in a single protein. These two facets of Ci-VSP activity have
      provided a unique model for studying how membrane potential is sensed by proteins
      and a novel mechanism for control of enzymatic activity. These facets make Ci-VSP
      a fascinating and versatile enzyme. Ci-VSP has a voltage sensing domain (VSD)
      that resembles those found in voltage-gated channels (VGC). The VSD resides in
      the N-terminus and is formed by four putative transmembrane segments. The fourth
      segment contains charged residues which are likely involved in voltage sensing.
      Ci-VSP produces sensing currents in response to changes in potential, within a
      defined range of voltages. Sensing currents are analogous to "gating" currents in
      VGC. As known, these latter proteins contain four VSDs which are entangled in a
      complex interaction with the pore domain - the effector domain in VGC. This
      complexity makes studying the basis of voltage sensing in VGC a difficult
      enterprise. In contrast, Ci-VSP is thought to be monomeric and its catalytic
      domain - the VSP's effector domain - can be cleaved off without disrupting the
      basic electrical functioning of the VSD. For these reasons, VSPs are considered a
      great model for studying the activity of a VSD in isolation. Finally, VSPs are
      also phosphoinositide phosphatases. Phosphoinositides are signaling lipids found
      in eukaryotes and are involved in many processes, including modulation of VGC
      activity and regulation of cell proliferation. Understanding VSPs as enzymes has
      been the center of attention in recent years and several reviews has been
      dedicated to this area. Thus, this review will be focused instead on the other
      face of this true JanusBifrons and recapitulate what is known about VSPs as
      electrically active proteins.

PMID- 22993509
TI  - A physiologically based, multi-scale model of skeletal muscle structure and
      function.
AB  - Models of skeletal muscle can be classified as phenomenological or biophysical.
      Phenomenological models predict the muscle's response to a specified input based
      on experimental measurements. Prominent phenomenological models are the Hill-type
      muscle models, which have been incorporated into rigid-body modeling frameworks,
      and three-dimensional continuum-mechanical models. Biophysically based models
      attempt to predict the muscle's response as emerging from the underlying
      physiology of the system. In this contribution, the conventional biophysically
      based modeling methodology is extended to include several structural and
      functional characteristics of skeletal muscle. The result is a physiologically
      based, multi-scale skeletal muscle finite element model that is capable of
      representing detailed, geometrical descriptions of skeletal muscle fibers and
      their grouping. Together with a well-established model of motor-unit recruitment,
      the electro-physiological behavior of single muscle fibers within motor units is
      computed and linked to a continuum-mechanical constitutive law. The bridging
      between the cellular level and the organ level has been achieved via a multi
      scale constitutive law and homogenization. The effect of homogenization has been
      investigated by varying the number of embedded skeletal muscle fibers and/or
      motor units and computing the resulting exerted muscle forces while applying the
      same excitatory input. All simulations were conducted using an anatomically
      realistic finite element model of the tibialis anterior muscle. Given the fact
      that the underlying electro-physiological cellular muscle model is capable of
      modeling metabolic fatigue effects such as potassium accumulation in the T
      tubular space and inorganic phosphate build-up, the proposed framework provides a
      novel simulation-based way to investigate muscle behavior ranging from motor-unit
      recruitment to force generation and fatigue.

PMID- 22993510
TI  - Phylodynamic analysis of a viral infection network.
AB  - Viral infections by sexual and droplet transmission routes typically spread
      through a complex host-to-host contact network. Clarifying the transmission
      network and epidemiological parameters affecting the variations and dynamics of a
      specific pathogen is a major issue in the control of infectious diseases.
      However, conventional methods such as interview and/or classical phylogenetic
      analysis of viral gene sequences have inherent limitations and often fail to
      detect infectious clusters and transmission connections. Recent improvements in
      computational environments now permit the analysis of large datasets. In
      addition, novel analytical methods have been developed that serve to infer the
      evolutionary dynamics of virus genetic diversity using sample date information
      and sequence data. This type of framework, termed "phylodynamics," helps connect
      some of the missing links on viral transmission networks, which are often hard to
      detect by conventional methods of epidemiology. With sufficient number of
      sequences available, one can use this new inference method to estimate
      theoretical epidemiological parameters such as temporal distributions of the
      primary infection, fluctuation of the pathogen population size, basic
      reproductive number, and the mean time span of disease infectiousness.
      Transmission networks estimated by this framework often have the properties of a
      scale-free network, which are characteristic of infectious and social
      communication processes. Network analysis based on phylodynamics has alluded to
      various suggestions concerning the infection dynamics associated with a given
      community and/or risk behavior. In this review, I will summarize the current
      methods available for identifying the transmission network using phylogeny, and
      present an argument on the possibilities of applying the scale-free properties to
      these existing frameworks.

PMID- 22993508
TI  - Being flexible: the voltage-controllable activation gate of kv channels.
AB  - Kv channels form voltage-dependent potassium selective pores in the outer cell
      membrane and are composed out of four alpha-subunits, each having six membrane
      spanning alpha-helices (S1-S6). The alpha-subunits tetramerize such that the S5
      S6 pore domains co-assemble into a centrally located K(+) pore which is
      surrounded by four operational voltage-sensing domains (VSD) that are each formed
      by the S1-S4 segments. Consequently, each subunit is capable of responding to
      changes in membrane potential and dictates whether the pore should be conductive
      or not. K(+) permeation through the pore can be sealed off by two separate gates
      in series: (a) at the inner S6 bundle crossing (BC gate) and (b) at the level of
      the selectivity filter (SF gate) located at the extracellular entrance of the
      pore. Within the last years a general consensus emerged that a direct
      communication between the S4S5-linker and the bottom part of S6 (S6(c))
      constitutes the coupling with the VSD thus making the BC gate the main voltage
      controllable activation gate. While the BC gate listens to the VSD, the SF
      changes its conformation depending on the status of the BC gate. Through the eyes
      of an entering K(+) ion, the operation of the BC gate apparatus can be compared
      with the iris-like motion of the diaphragm from a camera whereby its diameter
      widens. Two main gating motions have been proposed to create this BC gate
      widening: (1) tilting of the helix whereby the S6 converts from a straight alpha
      helix to a tilted one or (2) swiveling of the S6(c) whereby the S6 remains bent.
      Such motions require a flexible hinge that decouples the pre- and post-hinge
      segment. Roughly at the middle of the S6 there exists a highly conserved glycine
      residue and a tandem proline motif that seem to fulfill the role of a gating
      hinge which allows for tilting/swiveling/rotations of the post-hinge S6 segment.
      In this review we delineate our current view on the operation of the BC gate for
      controlling K(+) permeation in Kv channels.

PMID- 22993511
TI  - Electron tomography of the nucleoid of Gemmata obscuriglobus reveals complex
      liquid crystalline cholesteric structure.
AB  - The nucleoid of the planctomycete Gemmata obscuriglobus is unique within the
      Bacteria in being both highly condensed and enclosed by a double-membrane nuclear
      envelope, seemingly analogous to the nucleus of eukaryotes. Here we have applied
      electron tomography to study high-pressure frozen, cryosubstituted cells of G.
      obscuriglobus and found multiple nested orders of DNA organization within the
      condensed nucleoid structure. Detailed examination of the nucleoid revealed a
      series of nested arcs characteristic of liquid crystalline cholesteric DNA
      structure. The finest fibers were arranged in parallel concentrically in a double
      twist organization. At the highest order of nucleoid organization, several of
      these structures come together to form the core of the G. obscuriglobus nucleoid.
      The complex structure of DNA within this nucleoid may have implications for
      understanding the evolutionary significance of compartmentalized planctomycete
      cells.

PMID- 22993512
TI  - Molybdenum limitation of microbial nitrogen assimilation in aquatic ecosystems
      and pure cultures.
AB  - Molybdenum (Mo) is an essential micronutrient for biological assimilation of
      nitrogen gas and nitrate because it is present in the cofactors of nitrogenase
      and nitrate reductase enzymes. Although Mo is the most abundant transition metal
      in seawater (107 nM), it is present in low concentrations in most freshwaters,
      typically <20 nM. In 1960, it was discovered that primary productivity was
      limited by Mo scarcity (2-4 nM) in Castle Lake, a small, meso-oligotrophic lake
      in northern California. Follow up studies demonstrated that Mo also limited
      primary productivity in lakes in New Zealand, Alaska, and the Sierra Nevada.
      Research in the 1970s and 1980s showed that Mo limited primary productivity and
      nitrate uptake in Castle Lake only during periods of the growing season when
      nitrate concentrations were relatively high because ammonium assimilation does
      not require Mo. In the years since, research has shifted to investigate whether
      Mo limitation also occurs in marine and soil environments. Here we review studies
      of Mo limitation of nitrogen assimilation in natural microbial communities and
      pure cultures. We also summarize new data showing that the simultaneous addition
      of Mo and nitrate causes increased activity of proteins involved in nitrogen
      assimilation in the hypolimnion of Castle Lake when ammonium is scarce.
      Furthermore, we suggest that meter-scale Mo and oxygen depth profiles from Castle
      Lake are consistent with the hypothesis that nitrogen-fixing cyanobacteria in
      freshwater periphyton communities have higher Mo requirements than other
      microbial communities. Finally, we present topics for future research related to
      Mo bioavailability through time and with changing oxidation state.

PMID- 22993513
TI  - Bacterial Selection during the Formation of Early-Stage Aerobic Granules in
      Wastewater Treatment Systems Operated Under Wash-Out Dynamics.
AB  - Aerobic granular sludge is attractive for high-rate biological wastewater
      treatment. Biomass wash-out conditions stimulate the formation of aerobic
      granules. Deteriorated performances in biomass settling and nutrient removal
      during start-up have however often been reported. The effect of wash-out dynamics
      was investigated on bacterial selection, biomass settling behavior, and metabolic
      activities during the formation of early-stage granules from activated sludge of
      two wastewater treatment plants (WWTP) over start-up periods of maximum 60 days.
      Five bubble-column sequencing batch reactors were operated with feast-famine
      regimes consisting of rapid pulse or slow anaerobic feeding followed by aerobic
      starvation. Slow-settling fluffy granules were formed when an insufficient
      superficial air velocity (SAV; 1.8 cm s(-1)) was applied, when the inoculation
      sludge was taken from a WWTP removing organic matter only, or when reactors were
      operated at 30 degrees C. Fast-settling dense granules were obtained with 4.0 cm
      s(-1) SAV, or when the inoculation sludge was taken from a WWTP removing all
      nutrients biologically. However, only carbon was aerobically removed during start
      up. Fluffy granules and dense granules were displaying distinct predominant
      phylotypes, namely filamentous Burkholderiales affiliates and Zoogloea relatives,
      respectively. The latter were predominant in dense granules independently from
      the feeding regime. A combination of insufficient solid retention time and of
      leakage of acetate into the aeration phase during intensive biomass wash-out was
      the cause for the proliferation of Zoogloea spp. in dense granules, and for the
      deterioration of BNR performances. It is however not certain that Zoogloea-like
      organisms are essential in granule formation. Optimal operation conditions should
      be elucidated for maintaining a balance between organisms with granulation
      propensity and nutrient removing organisms in order to form granules with BNR
      activities in short start-up periods.

PMID- 22993514
TI  - Iron Biofortification and Homeostasis in Transgenic Cassava Roots Expressing the
      Algal Iron Assimilatory Gene, FEA1.
AB  - We have engineered the tropical root crop cassava (Manihot esculenta) to express
      the Chlamydomonas reinhardtii iron assimilatory gene, FEA1, in its storage roots
      with the objective of enhancing the root nutritional qualities. Iron levels in
      mature cassava storage roots were increased from 10 to 36 ppm in the highest iron
      accumulating transgenic lines. These iron levels are sufficient to meet the
      minimum daily requirement for iron in a 500 g meal. Significantly, the expression
      of the FEA1 gene in storage roots did not alter iron levels in leaves. Transgenic
      plants also had normal levels of zinc in leaves and roots consistent with the
      specific uptake of ferrous iron mediated by the FEA1 protein. Relative to wild
      type plants, fibrous roots of FEA1 expressing plants had reduced Fe (III) chelate
      reductase activity consistent with the more efficient uptake of iron in the
      transgenic plants. We also show that multiple cassava genes involved in iron
      homeostasis have altered tissue-specific patterns of expression in leaves, stems,
      and roots of transgenic plants consistent with increased iron sink strength in
      transgenic roots. These results are discussed in terms of strategies for the iron
      biofortification of plants.

PMID- 22993515
TI  - Mu killer-Mediated and Spontaneous Silencing of Zea mays Mutator Family
      Transposable Elements Define Distinctive Paths of Epigenetic Inactivation.
AB  - Mu killer contains a partial inverted duplication of the mudrA transposase gene
      and two copies of the terminal inverted repeat A (TIRA) region of the master MuDR
      element of maize. Mu killer can effectively silence single copy MuDR/Mu lines,
      and it is proposed that a ~4 kb hairpin RNA is generated by read through
      transcription from a flanking gene and that this transcript serves as a substrate
      for siRNA production. Mu killer was sequenced, except for a recalcitrant portion
      in the center of the locus, and shown to be co-linear with mudrA as originally
      proposed. The ability of the dominant Mu killer locus to silence a standard high
      copy number MuDR/Mu transposon line was evaluated. After two generations of
      exposure, about three quarters of individuals were silenced indicating reasonable
      effectiveness as measured by the absence of mudrA transposase transcripts. Mu
      killer individuals that effectively silenced MuDR expressed two short antisense
      transcripts. In contrast, Mu killer individuals that failed to silence MuDR
      expressed multiple sense transcripts, derived from read through transcription
      initiating in a flanking gene, but no antisense transcripts were detected.

PMID- 22993516
TI  - A methodology to identify and prioritize gene candidates for human disease.

PMID- 22993517
TI  - The effects of sociodemographic factors on psychiatric diagnosis.
AB  - OBJECTIVE: Several studies have reported that ethnic differences influence
      psychiatric diagnoses. Some previous studies reported that African Americans and
      Hispanics are diagnosed with schizophrenia spectrum disorders more frequently
      than Caucasians, and that Caucasians are more likely to be diagnosed with
      affective disorders than other ethnic groups. We sought to identify associations
      between sociodemographic factors and psychiatric diagnosis. METHODS: We
      retrospectively examined the medical records of all psychiatric inpatients (ages
      over 18 years) treated at Kern county mental hospital (n=2,051) between July 2003
      and March 2007 for demographic, clinical information, and discharge diagnoses.
      RESULTS: African American and Hispanic males were more frequently diagnosed with
      schizophrenia spectrum disorders than Caucasians, whereas Caucasian females were
      more frequently diagnosed with affective disorders than females in the other
      ethnic groups, suggesting that patient ethnicity and gender may influence
      clinical diagnoses. Demographic variables, that is, a lower education, failure of
      marriage, homelessness, and low quality insurance, were found to be significantly
      associated with a diagnosis of schizophrenia spectrum disorders after adjusting
      for clinical variables. And, the presence of a family psychiatric history,
      failure of marriage, not-homelessness, and quality insurance were found to be
      associated with a diagnosis of affective disorders. CONCLUSION: Our results show
      that these demographic factors, including ethnicity, have effects on diagnoses in
      psychiatric inpatients. Furthermore, these variables may help prediction of
      psychiatric diagnoses.

PMID- 22993518
TI  - The factors affecting the development of national identity as South korean in
      north korean refugees living in South Korea.
AB  - OBJECTIVE: This study aims to observe the factors that influence the development
      of national identity of North Korean refugees who have resettled in South Korea.
      METHODS: The study population was comprised of 500 North Korean refugees who
      immigrated to South Korea in 2007. The variables measured national identity as
      South Korean, a scale for discrimination perceived during daily life, a social
      for supporting social network, a for childhood trauma experience, traumatic
      experiences in North Korea, and traumatic experiences during the escape process.
      Factor analysis was conducted on the result from the scale for national identity
      as South Korean which produced 4 factors including national consciousness,
      positive emotions, positive values, and negative values. Multiple regression was
      done to identify how variables such as demographic data, discrimination, social
      network, and past trauma had influenced each of 4 factors. RESULTS: National
      identity was negatively related by traumatic experience during childhood,
      perceived discrimination, and positively influenced by social networks. Positive
      emotion was related negatively to education level in North Korea and perceived
      discrimination, but positively related to traumatic experiences in North Korea.
      Negative value was related positively age and perceived discrimination but
      negatively related to supporting social network. CONCLUSION: The results of this
      study suggests that promoting social networks, decreasing discrimination and
      healing past traumas were important factors for North Korean refugees in South
      Korea to facilitate a new national identity as a South Korean.

PMID- 22993519
TI  - The psychological problems of north korean adolescent refugees living in South
      Korea.
AB  - OBJECTIVE: As the number of North Korean adolescent refugees drastically
      increased in South Korea, there is a growing interest in them. Our study was
      conducted to evaluate the mental health of the North Korean adolescent refugees
      residing in South Korea. METHODS: The subjects of this study were 102 North
      Korean adolescent refugees in Hangyeore middle and high School, the public
      educational institution for the North Korean adolescent refugees residing in
      South Korea, and 766 general adolescents in the same region. The Korean version
      of Child Behavior Check List (K-CBCL) standardized in South Korea was employed as
      the mental health evaluation tool. RESULTS: The adolescent refugees group showed
      a significantly different score with that of the normal control group in the K
      CBCL subscales for sociality (t=29.67, p=0.000), academic performance (t=17.79,
      p=0.000), total social function (t=35.52, p=0.000), social withdrawal (t=18.01,
      p=0.000), somatic symptoms (t=28.85, p=0.000), depression/anxiety (t=13.08,
      p=0.000), thought problems (t=6.24, p=0.013), attention problems (t=4.14,
      p=0.042), internalized problems (t=26.54, p=0.000) and total problems (t=5.23,
      p=0.022). CONCLUSION: The mental health of the North Korean adolescent refugees
      was severe particularly in internalized problems when compared with that of the
      general adolescents in South Korea. This result indicates the need for interest
      in not only the behavior of the North Korean adolescent refugees but also their
      emotional problem.

PMID- 22993520
TI  - Standardization Study of the Korean Version of the Stages of Change Readiness and
      Treatment Eagerness Scale for Smoking Cessation (K-SOCRATES-S) and Its Predictive
      Validity.
AB  - OBJECTIVE: The purpose of the study was to develop the Korean version of the
      Stage of Change Readiness and Treatment Eagerness Scale for Smoking Cessation (K
      SOCRATES-S) based on the Korean version of the Stages of Readiness for Change and
      Eagerness for Treatment scale (K-SOCRATES). This paper also demonstrates its
      reliability and validity among patients with nicotine dependence in South Korea.
      METHODS: At seven healthcare promotion centers in Gyeonggi-do, 333 male smokers
      aged 20 to 70 who visited smoking cessation clinic were recruited for this study
      and the K-SOCRATES-S was administered. After three months, the number of
      respondents who successfully stopped smoking was assessed by testing their urine
      cotinine level. Subsequently, exploratory factor analysis was performed to verify
      the reliability and validity of the K-SOCRATES-S. Also, a logistic regression
      analysis was performed to examine the variables that can predict the successful
      cessation of smoking on subscales of the K-SOCRATES-S. RESULTS: Exploratory
      factor analysis of the K-SOCRATES-S showed that the scale consisted of three
      factors: Taking Steps, Recognition, and Ambivalence. The scales measuring Taking
      Steps and Recognition in this scale had a significantly positive correlation with
      the scores observed on Kim's smoking cessation motivation scale. The scales
      measuring Taking Steps and Recognition had a significantly negative correlation
      with Ambivalence. Overall, the results indicate that the K-SOCRATES-K scale
      showed high validity. CONCLUSION: The K-SOCRATES-S developed in the present study
      is highly reliable and valid for predicting a patient's likelihood of success in
      quitting smoking among patients who want to cease smoking.

PMID- 22993521
TI  - The early trauma inventory self report-short form: psychometric properties of the
      korean version.
AB  - OBJECTIVE: Experiencing traumatic events in childhood is related to various
      psychiatric problems in adulthood, and a comprehensive tool for measuring
      childhood trauma is necessary in this field. This study aimed to examine the
      psychometric properties, and factor structure of the Korean version of the Early
      Trauma Inventory Self Report-Short Form (ETISR-SF). ETISR-SF measures the
      childhood trauma, including physical, and emotional sexual abuse, as well as
      general traumas. METHODS: A clinical and nonclinical samples comprising of 97
      subjects from a local community, and 207 patients with the ETISR-SF, were
      assessed. Other tools, including the Childhood Trauma Questionnaire-Short Form
      (CTQ-SF), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory
      (BAI) were used to assess clinical symptoms. Additional data from 69 college
      students was used to examine the test-retest reliability. RESULTS: The original
      four-factor model was supported by the confirmatory factor analysis scale [chi(2)
      (351, n=304)=3374.025, p<0.001, TLI=0.969, CFI=0.972, RMSEA=0.030]. The ETISR-SF
      was found to be a reliable instrument (Cronbach's alpha=0.869). Comparison of the
      ETISR-SF scores discriminated the clinical group from that of the control group.
      The measure showed good convergent and divergent validity, in that the scores
      were correlated higher with the scores on the CTQ-SF (0.691) than with the scores
      on the BDI or BAI (0.424, 0.397 respectively). The ETISR-SF was found to be
      temporally stable, showing the moderate to high correlation (0.844). CONCLUSION:
      These findings suggest that the Korean version of the ETISR-SF appears to be a
      reliable and valid instrument for the measurement of reported childhood trauma.

PMID- 22993522
TI  - Evaluation of two circadian rhythm questionnaires for screening for the delayed
      sleep phase disorder.
AB  - OBJECTIVE: Delayed sleep phase disorder (DSPD) is a condition in which patients
      often fall asleep some hours after midnight and have difficulty waking up in the
      morning. Circadian chronotype questionnaires such as Horne-Ostberg Morningness
      Eveningness Questionnaire (MEQ) and Basic Language Morningness (BALM) scale have
      been used for screening for DSPD. This study was to evaluate these two chronotype
      questionnaires for screening of DSPD. METHODS: The study samples were 444 DSPD
      and 438 controls. Cronbach's alpha coefficient was calculated to evaluate for
      internal consistency. An exploratory factor analysis was conducted using
      principal-axis factoring. The diagnostic performance of a test was evaluated
      using Receiver Operating Characteristic (ROC) curve analysis. A discriminant
      function analysis was also performed. RESULTS: For internal consistency,
      Cronbach's alpha of 0.898 for BALM was higher than the 0.837 for MEQ, though both
      have acceptable internal consistency. BALM has better construct validity than the
      MEQ because some MEQ items measure different dimensions. However, when we
      evaluated the efficiency of two questionnaires for DSPD diagnosis by using the
      ROC curve, the BALM was similar to the MEQ. In a discriminant analysis with the
      BALM to classify the two groups (DSPD vs. normal), 6 items were identified that
      resulted in good classification accuracy. Upon examination of the classification
      procedure, 94.2% of the originally grouped cases were classified correctly.
      CONCLUSION: These findings suggest that the BALM has better psychometric
      properties than the MEQ in screening and discriminating DSPS.

PMID- 22993523
TI  - Patterns of Tobacco Consumption among Indian Men with Schizophrenia Compared to
      Their Male Siblings.
AB  - OBJECTIVE: Tobacco consumption among patients with schizophrenia has been
      investigated extensively in western countries, but there is a dearth of studies
      in India, where socio-economic and cultural variables are different. This study
      aims to investigate the patterns of tobacco consumption among schizophrenia
      patients compared with their non-psychotic siblings. METHODS: Consenting,
      successive male outpatients diagnosed with schizophrenia (n=100, DSM-IV
      criteria), and their non-psychotic brothers (n=100) were compared. Following a
      structured diagnostic interview, detailed information about tobacco consumption
      (including smokeless tobacco) was obtained using the Fagerstrom Test for Nicotine
      Dependence for smoked tobacco, and FTND-smokeless tobacco. The University of
      Pennsylvania Computerized Neurocognitive battery (CNB) was administered to a sub
      group of patients (n=48). RESULTS: Schizophrenia patients initiated tobacco use
      at a significantly earlier age than their brothers, but there was no significant
      difference with regard to type, quantity or frequency of tobacco use (smoke or
      smokeless varieties). Patients who consumed tobacco had significantly higher
      positive symptom scores compared with non-users (p=0.043). There were no
      significant differences between nicotine dependent and non-dependent patients
      with regard to CNB domains except attention. CONCLUSION: Patterns of tobacco
      consumption were similar among schizophrenia patients and their non-psychotic
      brothers. Tobacco use was associated with increased positive symptom scores, but
      there were no significant differences in cognitive measures among nicotine
      dependent and non-dependent patients.

PMID- 22993524
TI  - Effects of percutaneous coronary intervention on depressive symptoms in chronic
      stable angina patients.
AB  - OBJECTIVE: Depression is present in 1 of 5 outpatients with coronary artery
      disease (CAD), and a well-documented risk factor for recurrent cardiac events and
      mortality. We examined the impact of percutaneous coronary intervention (PCI), on
      depressive symptoms, in chronic stable angina (CSA) patients. METHODS: On
      prospective and non-randomized trial, consecutive CSA patients (n=171), who had
      undergone coronary angiography from January 2006 to December 2007, were included.
      Patients were subdivided into PCI and non-PCI groups, and then completed 21-item
      the Beck Depression Inventory II (BDI-II), at the baseline and pre-discharge, to
      assess the depressive symptoms. RESULTS: A total of 108 (63%) patients were
      assigned to the non-PCI group, and 63 (37%) patients to the PCI group. Using an
      independent t-test, we found that patients with PCI were significantly older (non
      PCI vs. PCI; 57+/-11 vs. 64+/-10, years, p<0.001), had more joint disease (12.0
      vs. 27.0%, p=0.013), more stroke history (5.6 vs. 17.5%, p=0.012) and higher
      incident of family history of cardiovascular disease (28.7 vs. 46.0%, p=0.025),
      but less religion (54.6 vs. 36.5%, p=0.002) and private health insurance (43.5
      vs. 20.6%, p=0.002). The mean difference of BDI-II score between the baseline and
      pre-discharge was higher in patients with PCI (OR: 1.266; 95% CI: 1.146-1.398,
      p<0.001). CONCLUSION: In conclusion, PCI contributes independently to higher risk
      of developing depressive symptoms in CSA patients during hospitalization; Routine
      assessment and management of PCI related depressive symptoms are justified.

PMID- 22993525
TI  - Titrating Optimal Dose of Osmotic-Controlled Release Oral Delivery (OROS)
      Methylphenidate and Its Efficacy and Safety in Korean Children with ADHD: A
      Multisite Open Labeled Study.
AB  - OBJECTIVE: This study was aimed to determine effectiveness and tolerability of
      Osmotic-controlled Release Oral delivery (OROS) methylphenidate (MPH) and its
      optimal dose administered openly over a period of up to 12 weeks in drug naive
      Korean children with ADHD. METHODS: Subjects (n=143), ages 6 to 18-years, with a
      clinical diagnosis of any subtype of ADHD were recruited from 7 medical centers
      in Korea. An individualized dose of OROS-MPH was determined for each subject
      depending on the response criteria. The subjects were assessed with several
      symptom rating scales in week 1, 3, 6, 9 and 12. RESULTS: 77 of 116 subjects
      (66.4%) achieved the criteria for response and the average of optimal daily dose
      for response was to 30.05+/-12.52 mg per day (0.90+/-0.31 mg/kg/d) at the end of
      the study. Optimal dose was not significantly different between ADHD subtypes,
      whereas, significant higher dose was needed in older aged groups than younger
      groups. The average of optimal daily dose for response for the subjects aged
      above 12 years old was 46.38+/-15.52 per day (0.81+/-0.28 mg/kg/d) compared to
      younger groups (p<0.01). No serious adverse effects were reported and the dose
      did not have a significant effect on adverse effects. CONCLUSION: Optimal mean
      dose of OROS-MPH was significantly different by age groups. Higher dose was
      needed in older aged groups than younger groups. Effectiveness and tolerability
      of OROS-MPH in symptoms of ADHD is sustained for up to 12 weeks.

PMID- 22993526
TI  - Adherence with electronic monitoring and symptoms in children with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: The primary aim of this study was to compare electronic monitoring
      with other measures of adherence to Osmotic-controlled Release Oral delivery
      System methylphenidate in children with attention-deficit hyperactivity disorder
      (ADHD). The secondary aim was to analyze the relationships between adherence and
      clinical factors, including ADHD symptoms. METHODS: Thirty-nine children
      diagnosed with ADHD were monitored for adherence to medication over the course of
      eight weeks. Medication adherence was assessed using the Medication Event
      Monitoring System (MEMS), which is a bottle cap with a microprocessor that
      records all instances and times that the bottle is opened; patient self-report;
      clinician rating; and pill count. Information, including demographic and clinical
      characteristics, symptom rating scale, and psychological test results, were also
      collected. The relationships between adherence and clinical factors, including
      ADHD rating scores of baseline and of the changes, were assessed. RESULTS: The
      rate of non-adherence measured by the MEMS was found to be 46.2%, which was
      considerably higher than those of the patient self-report (17.9%), clinician
      rating (31.7%), and pill count (12.8%) of non-adherence. The rate of adherence
      measured by the MEMS was not significantly associated with baseline symptom
      severity or symptom changes over the eight weeks, although non-adherent group
      showed more severe baseline symptoms and inferior improvement. CONCLUSION:
      Adherence as measured by the MEMS showed a discrepancy with other measures of
      adherence in patients with ADHD. The symptom severity and level of improvement
      were not related to adherence with MEMS. Further studies are needed to evaluate
      the variables that may impact medication adherence in children with ADHD.

PMID- 22993527
TI  - Serotonin 2A Receptor Gene Polymorphism in Korean Children with Attention
      Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: The purpose of this study was to investigate the association between
      the T102C polymorphism in the serotonin 2A receptor gene and attention
      deficit/hyperactivity disorder (ADHD) in Korean patients. METHODS: A total of 189
      Korean children with ADHD as well as both parents of the ADHD children and 150
      normal children participated in this study. DNA was extracted from blood samples
      from all of the subjects, and genotyping was conducted. Based on the allele and
      genotype information obtained, case-control analyses were performed to compare
      the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were
      used for family-based association testing (number of trios=113). Finally,
      according to the significant finding which was showed in the case-control
      analyses, the results of behavioral characterastics and neuropsychological test
      were compared between ADHD children with and without the C allele. RESULTS: In
      the case-control analyses, statistically significant differences were detected in
      the frequencies of genotypes containing the C allele (chi(2)=4.73, p=0.030). In
      the family-based association study, TDTs failed to detect linkage disequilibrium
      of the T102C polymorphism associated with ADHD children. In the ADHD children,
      both the mean reaction time and the standard deviation of the reaction time in
      the auditory continuous performance test were longer in the group with the C
      allele compared to the group without the C allele. CONCLUSION: The results of
      this study suggest that there is a significant genetic association between the
      T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.

PMID- 22993528
TI  - Pituitary volumes are reduced in patients with somatization disorder.
AB  - OBJECTIVE: Despite of the suggested physiological relationship between somatoform
      disorder and disturbances in HPA axis function no volumetric study of pituitary
      volumes in somatization disorder has been carried out. Therefore, we aimed to use
      structural MRI to evaluate the pituitary volumes of the patients with
      somatization disorder. METHODS: Eighteen female patients with somatization
      disorder according to DSM-IV and same number of healthy controls were included
      into the study. All subjects were scanned using a 1.5-T General Electric (GE;
      Milwaukee, USA) scanner. Pituitary volume measurements were determined by using
      manuallly tracings according to standard antomical atlases. RESULTS: It was found
      significantly smaller pituitary volumes of the whole group of somatization
      patients compared to healthy (t=-3.604, p=0.001). ANCOVA predicting pituitary
      volumes demonstrated a significant main effect of diagnostic group (F=13.530,
      p<0.001) but TBV (F=1.924, p>0.05) or age (F=1.159, p>0.05). It was determined
      that there was no significant correlation between smaller pituitary volumes and
      the duration of illness (r=0.16, p>0.05) in the patient group. CONCLUSION: In
      conclusion, we suggest that the patients with somatization disorder might have
      significantly smaller pituitary volumes compared to healthy control subjects.

PMID- 22993529
TI  - Changes in effective connectivity according to working memory load: an FMRI study
      of face and location working memory tasks.
AB  - OBJECTIVE: The functional strategic mechanisms in the brain during performing
      visuospatial working memory tasks, especially tasks with heavy load, are
      controversial. We conducted the functional magnetic resonance imaging (fMRI)
      while sixteen subjects were performing face- and location-matching n-back tasks
      to examine causal relations within the frontoparietal networks. METHODS: We
      applied a sophisticated method, the structural equation modeling (SEM), to the
      fMRI data. The imaging data were analyzed by extracting the task-related
      eigenseries using the principal component analysis (PCA) and then by applying a
      form of data-driven model called the automated search method. RESULTS: The SEM
      analyses revealed a functional shift of network connectivity from the right to
      the left hemisphere with increasing load in the face-matching n-back tasks while
      the location-matching tasks required bilateral activation. In the locating
      matching n-back tasks, a pattern of parallel processing was observed in the left
      phonological loop and the right inferior parietal regions. Furthermore, object
      working memory-related activities in the left hemisphere reliably contributed to
      performance of both the face- and location-matching 2-back tasks. CONCLUSION: Our
      results are consistent with previous reports in terms of demonstrating parallel
      and distributed information processing during performing working memory tasks
      with heavy loads. Our results additionally suggest a dynamic shift between the
      fast imagery circuit (right hemisphere) and the stable verbal circuit (left
      hemisphere), depending on task load.

PMID- 22993530
TI  - Temperament affects sympathetic nervous function in a normal population.
AB  - OBJECTIVE: Although specific temperaments have been known to be related to
      autonomic nervous function in some psychiatric disorders, there are few studies
      that have examined the relationship between temperaments and autonomic nervous
      function in a normal population. In this study, we examined the effect of
      temperament on the sympathetic nervous function in a normal population. METHODS:
      Sixty eight healthy subjects participated in the present study. Temperament was
      assessed using the Korean version of the Cloninger Temperament and Character
      Inventory (TCI). Autonomic nervous function was determined by measuring skin
      temperature in a resting state, which was recorded for 5 minutes from the palmar
      surface of the left 5th digit using a thermistor secured with a Velcro(r) band.
      Pearson's correlation analysis and multiple linear regression were used to
      examine the relationship between temperament and skin temperature. RESULTS: A
      higher harm avoidance score was correlated with a lower skin temperature (i.e. an
      increased sympathetic tone; r=-0.343, p=0.004) whereas a higher persistence score
      was correlated with a higher skin temperature (r=0.433, p=0.001). Hierarchical
      linear regression analysis revealed that harm avoidance was able to predict the
      variance of skin temperature independently, with a variance of 7.1% after
      controlling for sex, blood pressure and state anxiety and persistence was the
      factor predicting the variance of skin temperature with a variance of 5.0%.
      CONCLUSION: These results suggest that high harm avoidance is related to an
      increased sympathetic nervous function whereas high persistence is related to
      decreased sympathetic nervous function in a normal population.

PMID- 22993532
TI  - A case of right cerebellopontine-angle lesion: psychotic symptoms and magnetic
      resonance imaging findings.
AB  - Here, we report psychotic symptoms together with a right cerebellopontine-angle
      lesion. A37-year-old female patient presented with a trigeminal Schwannoma
      occupying the right cerebellopontine angle. Her psychotic symptoms included
      auditory hallucinations and delusions of persecution. T1- and T2-weighted images
      on magnetic resonance imaging (MRI) revealed hyperintense and hypointense areas
      in the right cerebellopontine angle, respectively. The clinical and neuroimaging
      reviews in this case suggest that sudden onset of psychotic symptoms at a mature
      age may be associated with a right cerebellopontine-angle lesion and that MRI
      should be used to evaluate possible organic bases in patients that present with
      psychosis.

PMID- 22993531
TI  - Serotonergic dysfunction in patients with bipolar disorder assessed by the
      loudness dependence of the auditory evoked potential.
AB  - OBJECTIVE: The loudness dependence of the auditory evoked potential (LDAEP) is
      suggested to be a marker of serotonin system function. This study explored the
      LDAEP of multiple mood statuses (depression, mania, and euthymia) and its
      clinical implication in bipolar disorder patients. METHODS: A total of 89
      subjects, comprising 35 patients with bipolar disorder, 32 patients with
      schizophrenia, and 22 healthy controls were evaluated. The bipolar disorder cases
      comprised 10 depressed patients, 15 patients with mania, and 10 euthymic
      patients. The N1/P2 peak-to-peak amplitudes were measured at 5 stimulus
      intensities, and the LDAEP was calculated as the slope of the linear regression.
      Both cortical and source LDAEP values were calculated. RESULTS: LDAEP varied
      according to mood statuses, and was significantly stronger in cases of euthymia,
      depression, and mania. Cortical LDAEP was significantly stronger in patients with
      bipolar euthymia compared with schizophrenia, stronger in bipolar depression than
      in schizophrenia, stronger in healthy controls than in schizophrenia patients,
      and stronger in healthy controls than in patients with bipolar mania. Source
      LDAEP was significantly stronger in patients with bipolar euthymia, bipolar
      depression, and bipolar mania compared with schizophrenia, stronger in bipolar
      euthymia than in bipolar mania. Psychotic features weakened the source LDAEP
      relative to nonpsychotic features. The severity of the depressive symptom was
      negatively correlated with source LDAEP. CONCLUSION: These findings suggest that
      the serotonin activity of patients with bipolar disorder may vary according to
      mood status. A longitudinal follow-up study should be pursued using drug-naive
      subjects.

PMID- 22993533
TI  - Prevalence of human papilloma virus in cytological abnormalities: Association of
      risk factors and cytomorphological findings.
AB  - BACKGROUND: Previous studies demonstrated the etiological role of human papilloma
      virus (HPV) in cervical carcinogenesis. Assessing the distribution of HPV may
      elucidate these observations. MATERIALS AND METHODS: In total, we examined 3839
      specimens, of which 187 abnormally classified cervical smears were immunostained
      using the p16(INK4A) assay. DNA was extracted from 182 specimens, and polymerase
      chain reaction (PCR) was performed. Participants' socio-demographics, sexual and
      reproductive history, HIV status, contraceptive use, and Pap smear history were
      recorded. RESULTS: Subject ages, number of sexual partners, and age at first
      sexual encounter ranged from 15 to 49 years, from 1 to 37 partners, and from 13
      to 34 years, respectively. P16 immunoreactivity was detected in 60.4% of cases.
      The distribution of epithelial lesions and P16 overexpression (bracketed) was: 28
      (5) atypical squamous cells of undetermined significance (ASC-US), 96 (50) lower
      grade squamous intraepithelial lesion (LSIL), 9 (7) atypical squamous cells
      cannot exclude HSIL (ASC-H), and 54 (51) higher grade squamous intraepithelial
      lesion (HSIL). Ninety-four percent of HSIL expressed P16. Fifty-two percent of
      LSIL expressed P16. P16 expression declined from 61% (25-34 year age group) to 5%
      (45-49 year age group) for different age groups. HPV-DNA by PCR was detected in
      94.5% of P16-positive samples. Type-specific PCR (HPV 16 and 18) was found in
      12.2% and 14.5% of abnormal lesions, respectively. Younger age at first sexual
      encounter and HIV infection predominated in HPV type(s) 16 and/or 18 positive
      subjects. CONCLUSION: This study reinforced the value of the p16(INK4A) surrogate
      marker in identifying women with progressive cervical disease.

PMID- 22993534
TI  - Adult rhabdomyoma: A challenging diagnosis on cytology.

PMID- 22993536
TI  - Novel strategy with acidic arginine solution for the treatment of influenza A
      virus infection.
AB  - There is already an indication of a potential worldwide spread of influenza
      projected for this coming autumn and winter. In this review, we propose an
      aqueous arginine solution as a novel agent for preventive measures and possible
      chemotherapy against influenza A virus infection. Influenza A virus spreads among
      the human population through both droplets and direct contact, and hand and mouth
      wash are the primary preventive measures. Upon contact, influenza A virus infects
      epithelial cells of the upper respiratory tracts in the initial phase of
      infection and spreads over the mucosal surface of the tracts, leading to varying
      degrees of inflammation near the site of infection. Arginine inactivates
      enveloped viruses, including influenza virus at an acidic pH or elevated
      temperature and hence may be used for preventive measures as a disinfectant and
      also for treatment of the infection. Because of the low cytotoxicity of arginine,
      virus inactivation may be performed at the site of infection in the form of a
      liquid or spray of an aqueous arginine solution. Acidic solvents have been used
      as a disinfectant and, to a limited extent, as a virus inactivation agent.
      Arginine may have the edge over acidic solvents due to its safety, or at least it
      may be used as an alternative option to acidic solvents or more specific
      antiviral drugs. Arginine as well as acidic solvents use a virus inactivation
      mechanism fundamentally different from the mechanism of antiviral
      chemotherapeutic drugs, i.e., through weak, but multiple, interactions with viral
      components. This eliminates the possibility of generating resistant viruses
      against arginine treatments.

PMID- 22993535
TI  - Dietary factors, genetic and epigenetic influences in colorectal cancer.
AB  - Genetic influences, together with epigenetic components and dietary factors, play
      a fundamental role in the initiation and progression of cancer by causing a
      number of deregulations. Colorectal cancer (CRC) is a disease influenced by
      dietary factors, for which established genetic and epigenetic alterations have
      been identified. Within CRC, there are hereditary syndromes that present
      mutations in the germ-line hMLH1, and also alterations in the methylation of the
      promoters. Epigenetics has also been established as a pathway of carcinogenesis.
      In the present review, we analyzed studies conducted to discern the different
      pathways leading to established CRC, stressing the importance of identifying
      factors that may predict CRC at an early stage, since it is mostly a silent
      disease observed at the clinical level in advanced stages.

PMID- 22993538
TI  - Curcumin for the prevention of progression in monoclonal gammopathy of
      undetermined significance: A word of caution.
AB  - A recent pilot study found that curcumin, in certain patients with monoclonal
      gammopathy of undetermined significance (MGUS), decreases the paraprotein load
      and the urinary N-telopeptide of type 1 collagen bone turnover marker. While this
      result is encouraging, the easy availability of the food component turmeric,
      containing curcumin, may lead to intake by MGUS patients without medical
      supervision. Curcumin is generally considered safe. Nevertheless, it is known
      that curcumin inhibits interleukin-12 production in dendritic cells, thereby
      dampening the Th1 response. It is also well established that Th1 cells are
      protective against invading pathogens and tumors. The present study describes a
      case in which bronchitis developed upon turmeric intake for gastrointestinal
      complaints. While one case does not provide proof of curcumin toxicity, a
      thorough literature overview suggests that turmeric may have an immunosuppressive
      effect, notably in patients with a compromised immune system. A warning against
      the use of turmeric or curcumin without medical supervision in immunocompromised
      patients seems therefore very opportune. Patients with MGUS, in whom the levels
      of non-affected immunoglobulins are reduced, should be carefully monitored for
      toxicity when curcumin is administered.

PMID- 22993537
TI  - The use of Cox-2 and PPARgamma signaling in anti-cancer therapies.
AB  - Increased production of the pro-inflammatory enzyme cyclooxygenase-2 (Cox-2) and
      altered expression and activity of peroxisome proliferator-activated receptor
      gamma (PPARgamma) have been observed in many malignancies. Both the PPARgamma
      ligands and the Cox-2 inhibitors possess anti-inflammatory and anti-neoplastic
      effects in vitro and have been assessed for their therapeutic potential in
      several pre-clinical and clinical studies. Recently, multiple interactions
      between PPARgamma and Cox-2 signaling pathways have been revealed. Understanding
      of the cross-talk between PPARgamma and Cox-2 might provide important novel
      strategies for the effective treatment and/or prevention of cancer. This article
      summarizes recent achievements involving the functional interactions between the
      PPARgamma and Cox-2 signaling pathways and discusses the implications of such
      interplay for clinical use.

PMID- 22993540
TI  - Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis.
AB  - To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted
      water (DDW) on human lung cancer and the possible mechanisms underlying these
      effects, we cultured and treated human lung carcinoma cell line A549 and human
      embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72
      h. Cellular growth inhibition rates were determined using the 3-(4, 5
      dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (MTT) proliferation assay.
      A549 cells were treated with 50+/-5 ppm DDW, and the morphology and structure of
      cells were observed by scanning electron microscopy (SEM). We observed
      alterations in the cellular skeleton by transmission electron microscopy (TEM)
      and changes in cell cycle by flow cytometry. Our data showed that DDW
      significantly inhibited the proliferation of A549 cells at a specific time point,
      and cells demonstrated the characteristic morphological changes of apoptosis
      under SEM and TEM. The length of the S phase increased significantly in cells
      treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were
      decreased. We observed DDW-induced cellular apoptosis using terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragment
      analyses. In addition, we established a tumor transplantion model by injecting
      H460 tumor cells into subcutaneous tissue of BALB/c mice treated with DDW for 60
      days. We determined the tumor inhibition rate of treated and control groups and
      found that the tumor weight was significantly decreased and the tumor inhibition
      rate was approximately 30% in the DDW group. We conclude that DDW is a promising
      new anticancer agent with potential for future clinical application.

PMID- 22993539
TI  - EML4-ALK fusion transcripts in immunohistochemically ALK-positive non-small cell
      lung carcinomas.
AB  - EML4-ALK fusion transcripts have been found in a subset of non-small cell lung
      carcinomas (NSCLCs); however, their protein expression status has not yet been
      fully elucidated. In this study we investigated ALK protein expression in 302
      NSCLCs and 291 gastric carcinomas by means of immunohistochemical analysis.
      Twelve (4.0%) NSCLCs, but none of the gastric carcinomas, were found to be
      positive for ALK. The ALK signal was detected in the cytoplasm of cancer cells.
      Subsequent RNA analysis of 10 RNA-available, immunohistochemically ALK-positive
      tumors revealed that three tumors had EML4-ALK variant 1, three tumors had
      variant 2, three tumors had variants 3a and 3b, and one tumor had a novel variant
      in which exon 14 of EML4 is connected to the nucleotide at position 53 of exon 20
      of ALK by a 2-bp insertion. These results suggest that immunohistochemical ALK
      detection is a useful way to screen NSCLCs for tumors containing ALK fusions.

PMID- 22993541
TI  - Macrophage involvement in Epstein-Barr virus-related tumors.
AB  - Epstein-Barr virus (EBV) is known as a causative agent of Burkitt's lymphoma,
      nasopharyngeal carcinoma and approximately 10% of stomach carcinoma cases. In
      other human cancers, EBV gene expression including lytic infection protein
      detected using in situ hybridization and immunofluorescence staining has been
      reported. Moreover, the expression and replication of EBV genes in cultured
      normal macrophages and in histiocytes of Langerhans' cell histiocytosis have been
      identified. The aim of this study was to examine EBV expression in macrophages in
      other EBV-associated human tumors. Forty-one cases of EBV-associated tumors,
      which had been confirmed to express EBV, were examined. Tissue sections after in
      situ hybridization were double-stained immunohistochemically with the monoclonal
      anti-CD68 antibody. EBV expression in macrophages in the lesions of
      nasopharyngeal carcinoma, oral cancer, thyroid carcinoma, renal cell carcinoma,
      testicular carcinoma, uterine carcinoma, cutaneous T-cell lymphoma and anaplastic
      large-cell lymphoma was identified, whereas macrophages in normal or non
      cancerous lesions showed no EBV expression. Many tumor-associated macrophages in
      EBV-related tumors carry EBV, which appears to induce the EBV lytic infection of
      macrophages. Therefore, the possibility that the lytic infection of macrophages
      by EBV and the resulting inflammation play certain roles in the oncogenesis of
      EBV-associated human tumors was raised.

PMID- 22993543
TI  - Electrolyte and protein imbalance following anti-EGFR therapy in cancer patients:
      A comparative study.
AB  - Electrolytic changes in blood have been associated with the use of anti-epidermal
      growth factor receptor (EGFR) antibodies. The objective of this retrospective
      study was to compare the rate of incidence and the severity of blood electrolyte
      and protein imbalances occurring in patients receiving cetuximab or panitumumab
      with or without concurrent chemotherapy. Treatment data of 58 patients who
      received cetuximab and 21 patients who received panitumumab were analyzed.
      Cetuximab caused hypomagnesemia in more than half of the patients, among whom 4
      had severity up to grade 2/3 level, whereas panitumumab induced hypomagnesemia in
      90% of the patients with severity up to grade 2 level occurring in 38% of the
      patients. Intravenous magnesium supplementation on the day of anti-EGFR treatment
      did not always adequately control the magnesium wasting in these patients. Often
      treatments with these agents had to be interrupted or terminated as a result of
      severe electrolyte depletion despite supplementation. Taking into consideration
      the mechanism of magnesium wasting from the kidney and the magnesium transport
      process in the gut, intravenous magnesium infusion coupled with oral
      supplementation with more tolerant oral magnesium products may help improve the
      treatment outcome in these patients. Surprisingly, more than half of these
      patients showed significant decreases in their albumin levels, which were
      correlated with the initiation or discontinuation of anti-EGFR therapy. The
      underlying mechanism of this decrease in albumin level is not known. The
      increased likelihood of poor outcomes such as mortality, morbidity and prolonged
      hospital stay in acutely ill patients with hypoalbuminemia is well recognized.
      Moreover, the maintenance of adequate serum albumin levels in these patients
      receiving anti-EGFR therapy may play an important role in containing some of the
      adverse effects of concurrently administered chemotherapeutic agents.

PMID- 22993542
TI  - Telmisartan inhibits human urological cancer cell growth through early apoptosis.
AB  - Angiotensin II receptor blockers (ARBs) are widely used as hypertensive
      therapeutic agents. In addition, studies have provided evidence that ARBs have
      the potential to inhibit the growth of several types of cancer cells. It was
      reported that telmisartan (a type of ARB) has peroxisome proliferator-activated
      receptor (PPAR)-gamma activation activity. We previously reported that the PPAR
      gamma ligand induces growth arrest in human urological cancer cells through
      apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs
      on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC),
      prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory
      effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and
      losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated
      using an MTT assay. Flow cytometry and Hoechst staining were used to determine
      whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition
      in the urological cancer cells in a dose- and time-dependent manner. Urological
      cancer cells treated with 100 MUM telmisartan underwent early apoptosis and DNA
      fragmentation. However, the other ARBs had no effect on cell proliferation in any
      of the urological cancer cell lines. Telmisartan may mediate potent anti
      proliferative effects in urological cancer cells through PPAR-gamma. Thus,
      telmisartan is a potent target for the prevention and treatment of human
      urological cancer.

PMID- 22993544
TI  - Soluble mesothelin-related protein in pleural effusion from patients with
      malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm primarily
      arising from surface serosal cells of the pleura and is strongly associated with
      asbestos exposure. Patients with MPM often develop pleural fluid as initial
      presentation. However, cytological diagnosis using pleural fluid is usually
      difficult and has limited utility. A useful molecular marker for differential
      diagnosis particularly with lung cancer (LC) is urgently needed. The aim of the
      present study was to investigate the diagnostic value of soluble mesothelin
      related protein (SMRP) in pleural fluid. Pleural fluids were collected from 23
      patients with MPM, 38 with LC, 26 with benign asbestos pleurisy (BAP), 5 with
      tuberculosis pleurisy (TP) and 4 with chronic heart failure (CHF), and the SMRP
      concentration was determined. All data were analyzed by using non-parametric two
      sided statistical tests. The median concentration of SMRP in MPM, LC, BAP, TP and
      CHF were 11.5 (range 0.90-82.80), 5.20 (0.05-36.40), 6.65 (1.45-11.25), 3.20
      (1.65-6.50) and 2.03 (1.35-2.80) nmol/l, respectively. The SMRP concentration was
      significantly higher in MPM than in the other diseases (P=0.001). The area under
      the ROC curve (AUC) values of the MPM diagnosis was 0.75 for the differential
      diagnosis from the other groups. Based on the cut-off value of 8 nmol/l, the
      sensitivity and specificity for diagnosis of MPM were 70.0 and 68.4%,
      respectively. These results indicate that the SMRP concentration in pleural fluid
      is a useful marker for the diagnosis of MPM.

PMID- 22993545
TI  - Leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus
      irinotecan as individualized first-line therapy based on a drug sensitivity test.
AB  - The purpose of this study was to determine the effect of the addition of
      oxaliplatin (l-OHP) or irinotecan (SN-38) to 5-fluorouracil (5-FU) using the
      collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to establish
      whether leucovorin plus 5-FU should be administered in combination with l-OHP
      (FOLFOX) or SN-38 (FOLFIRI) in individualized first-line chemotherapy for the
      treatment of advanced colorectal cancer (CRC). Specimens of primary tumors were
      obtained from 24 CRC patients who had received no preoperative chemotherapy. CD
      DST was performed, and the inhibition rate (IR) was obtained under multiple
      incubation conditions. The effects of addition of l-OHP or SN-38 were evaluated
      for the same area under the concentration curve (AUC) of 5-FU based on linear
      regression analysis. Approximate expression and correlation coefficients (5-FU
      vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=72 and 5-FU vs. 5-FU + l
      OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=144) were y=0.94x+8.53 (R(2)=0.95,
      p<0.0004), y=0.77x+26.18 (R(2)=0.76, p<0.0004) and y= 0.91x+10.90 (R(2)=0.94,
      p<0.0004), y=0.52x+44.61 (R(2)=0.60, p<0.0004), respectively. Approximate
      expression of 5-FU vs. 5-FU + l-OHP almost fit the regression line (y=x+b(1)).
      This suggests that addition of l-OHP yields a constant additive effect,
      independent of the IR of 5-FU. However, approximate expression of 5-FU vs. 5-FU +
      SN-38 fit the regression line (y=ax+b(2), a<1, b(2)>=b(1)). This suggests that
      addition of SN-38 yields a greater additive effect due to the lower IR of 5-FU.
      These results indicate that FOLFIRI should be selected as the first-line
      chemotherapy for the treatment of poor responders to 5-FU.

PMID- 22993546
TI  - Gene expression and effects of orally active derivatives of fluoropyrimidine on
      gastric and colorectal cancer.
AB  - The effects of chemotherapy on gastrointestinal cancer are influenced by the
      chemotherapeutic sensitivity of the cancer cells. Determining the expression of
      genes related to chemotherapeutic sensitivity has been used as a molecular
      method. The aim of the study was to clarify the relationships between the
      expression of genes related to chemotherapeutic sensitivity and the effects of
      orally active derivatives of fluoropyrimidine on gastric and colorectal cancer.
      Forty-five patients who underwent adjuvant chemotherapy containing orally active
      derivatives of fluoropyrimidine after undergoing curative surgery for gastric or
      colorectal cancer were enrolled. Twenty-four patients had colorectal cancer and
      21 patients had gastric cancer. Total RNA was extracted from formalin-fixed,
      paraffin-embedded specimens of the resected tumors, and the expression of 11
      genes was measured using the RT-PCR method. We then analyzed the relationships
      between the gene expression and the postoperative relapse rate as well as the
      relationships between clinicopathological factors and postoperative relapse rate.
      The median observation period of the subjects was 41 months. Twelve out of the 21
      gastric cancer patients (57%) and 11 out of the 24 colorectal cancer patients
      (46%) relapsed. Although the results of a univariate analysis revealed that
      expression of none of the evaluated genes was related to relapse in the gastric
      cancer patients, excision repair cross-complementing gene 1 (ERCC1)
      overexpression was related to the relapse rate in colorectal cancer patients
      (p=0.023). When 1.295 was set as the cut-off value for ERCC1 overexpression using
      the receiver operating characteristic (ROC) curve, 67% of patients with ERCC1
      overexpression and 25% of patients without ERCC1 overexpression relapsed. The
      relapse-free survival rate was lower in the group with ERCC1 overexpression than
      in the group without ERCC1 overexpression (p=0.046). ERCC1 overexpression appears
      to be a useful predictor of relapse in colorectal cancer patients receiving
      adjuvant therapy with regimens including orally active derivatives of
      fluoropyrimidine.

PMID- 22993547
TI  - Effect of fibroblast growth factor-2 on periodontal ligament cells derived from
      human deciduous teeth in vitro.
AB  - A blood supply is crucial for tissue healing and regeneration. Periodontal
      ligament (PDL) tissue is situated between the tooth root and alveolar bone, and
      cells derived from PDL tissue are reported to have stem cell-like activity. This
      study aimed to evaluate the potential of PDL cells derived from deciduous teeth
      to express endothelial cell (EC)-specific markers. Using quantitative PCR, we
      investigated whether PDL cells derived from human deciduous teeth express mRNA
      for the EC-specific markers: vascular endothelialcadherin (VE-cadherin), vascular
      endothelial growth factor receptor 2 (VEGFR2) and CD31 upon treatment with 15
      ng/ml heparin or 10 ng/ml fibroblast growth factor (FGF)-2 in vitro. Quantitative
      PCR showed that PDL cells expressed mRNA for the EC-specific markers, VE-cadherin
      and VEGFR2, when cultured in the presence of heparin alone or with FGF-2. By
      contrast, marked CD31 mRNA expression was induced only when PDL cells were
      cultured with both heparin and FGF-2. Western blot analysis showed that the CD31
      protein was induced in PDL cells upon treatment with both heparin and FGF-2 for 3
      weeks. PDL cells derived from deciduous teeth inducibly express EC-specific
      markers and thus have the potential to differentiate into a vascular cell
      lineage.

PMID- 22993548
TI  - Role of inhibitor of DNA binding-1 protein is related to angiogenesis in the
      tumor advancement of uterine endometrial cancers.
AB  - The inhibitor of DNA binding (ID)-1 protein, an inhibitor of basic helix-loop
      helix transcription factors, has been found to be involved in multiple cellular
      functions. In the present study, ID-1 histoscores and mRNA levels were both
      significantly (p<0.05) increased in uterine endometrial cancers according to
      clinical stage, histological grade and depth of myometrial invasion. Furthermore,
      the 60-month survival rate of the 25 patients with high ID-1 was poor (52%),
      while that of the other 25 patients with low ID-1 was significantly higher (80%)
      (p<0.05). ID-1 histoscores and mRNA levels significantly (p<0.0001) correlated
      with microvessel counts in uterine endometrial cancers. Therefore, ID-1 acts on
      tumor advancement via angiogenic activity and can be considered a candidate
      prognostic indicator in uterine endometrial cancers.

PMID- 22993549
TI  - Serological levels of mutated p53 protein are highly detected at early stages in
      breast cancer patients.
AB  - The aim of this study was to compare the sensitivity of the serological level of
      anti-p53 antibodies in breast cancer patients and to correlate its expression
      level with patient age, histological stage and grade of tumor differentiation.
      Total p53 protein expression (mutant and wild-type) was also determined in the
      breast cancer tissues using immunohistochemistry (IHC). The serological levels of
      mutant p53 expression were found to be age-dependent, reaching the highest level
      at 50 years of age. Faint or low detection was observed in patients <=30 years of
      age. Anti-p53-antibodies were detected in patients <=40 and >=61 years of age.
      The serological levels of mutant p53 protein were highly detected in all stages
      of breast cancer, including the early stages. However, anti-p53 antibodies
      reached a high level of detection only in stage III breast carcinomas. No
      expression was found in patients with benign breast disease. The detection of p53
      mutations was dependent on the grade of tumor differentiation, achieving the
      highest level in the poorly differentiated breast carcinomas. Results from IHC
      were highly correlated with serological p53 mutational analysis. Our findings
      indicate that mutant p53 in serum is a promising novel parameter for the
      evaluation of cellular biology and the prognosis of breast cancer from its early
      stages using blood samples. Anti-p53 antibodies were demonstrated to be less
      sensitive in this study. It is also possible to use the expression of mutant p53
      protein as a molecular marker to differentiate benign breast disease from breast
      carcinoma prior to surgery.

PMID- 22993550
TI  - Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2
      interactions.
AB  - We generated replication-defective adenovirus Ad-p53AIP1 and studied its anti
      tumor efficacy both in vitro and in vivo. We demonstrated that Ad-p53AIP1
      infection elicited high levels of p53AIP1 expression in cancer cells. We also
      found that Ad-p53AIP1 expression induced marked apoptosis and cell cycle arrest
      in HepG2 cells. Moreover, Ad-p53AIP1 infection significantly inhibited the
      tumorigenesis of 4T1 mouse mammary cancer cells in vivo. In particular, we
      discovered that p53AIP1 overexpression up-regulated the protein levels of p53 in
      HepG2 cells, which was accompanied by down-regulation of MDM2 mRNA and protein,
      suggesting an interaction between MDM2 and p53 in p53AIP1-induced apoptosis and
      cell cycle arrest. Our data demonstrated the feasibility of Ad-p53AIP1-mediated
      cancer gene therapy. p53AIP1-induced up-regulation of p53 protein through MDM2
      suggests that p53AIP1 gene therapy may be more advantageous in tumors expressing
      high levels of oncoprotein MDM2 or having a mutation in MDM2 inhibitor p16INK4.

PMID- 22993551
TI  - Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent
      colorectal cancer cells.
AB  - Thymoquinone (TQ), the major compound of black seed oil, has been shown to induce
      pro-apoptotic signaling pathways in various human cancer models. Although TQ is
      commonly used in traditional medicine, its use in humans is limited due to its
      chemical properties and poor membrane penetration capacity. We therefore attached
      saturated and unsaturated fatty acid residues to TQ and evaluated the effect on
      cell proliferation, apoptosis and underlying signaling pathways in HCT116 and
      HCT116(p53-/-) colon cancer and HepG2 hepatoma cells in vitro. Treatment with
      thymoquinone-4-alpha-linolenoylhydrazone (TQ-H-10) or thymoquinone-4
      palmitoylhydrazone (TQ-H-11) induced a cytostatic effect, particularly in p53
      competent HCT116 cells, mediated by an up-regulation of p21(cip1/waf1) and a down
      regulation of cyclin E, and associated with an S/G(2) arrest of the cell cycle.
      Cells lacking p53 (HCT116(p53-/-)) or HepG2 liver cancer cells showed only a
      minor response to TQ-H-10. These findings demonstrate that derivatives of TQ
      inhibit cell proliferation dependent on p53 status by activating the cell cycle
      inhibitor p21(cip1/waf1) at lower concentrations than unmodified TQ. Structural
      modifications can therefore contribute to the further clinical development of TQ.

PMID- 22993552
TI  - Genetic and epigenetic alterations of RIZ1 and the correlation to
      clinicopathological parameters in liver fluke-related cholangiocarcinoma.
AB  - The retinoblastoma interacting zinc finger (RIZ1) gene is adjacent to D1S228
      where microsatellite instability has been associated with poor patient survival
      in liver fluke-associated cholangiocarcinoma (CCA). An understanding of the
      molecular mechanisms underlying the carcinogenesis and pathogenesis of CCA is
      necessary to improve patient survival. Therefore, we determined the genetic and
      epigenetic alterations of RIZ1 in 81 CCA samples and 69 matched non-tumor
      tissues. Methylation was found in 31 of 81 (38%) tumor samples and in 5 of 69
      (7%) matched non-tumor tissues. Frameshift mutations (2 of 81) and loss of
      heterozygosity (LOH) (14 of 81) were not common. Statistical analysis found no
      significant correlation between RIZ1 alterations and clinicopathological
      features, but RIZPro704 LOH was associated with patient survival in the
      multivariate analysis. RIZ1 hypermethylation may be one of the crucial molecular
      events contributing to cholangiocarcinogenesis, and RIZPro704 LOH may adversely
      impact patient survival. The biological function of RIZ1 in CCA should be further
      investigated in order to verify its potential role in regulating this cancer.

PMID- 22993553
TI  - Role of immunohistochemistry and apoptosis as investigative tools in assessing
      the prognosis of patients with prostate tumours.
AB  - Apoptosis is a form of programmed cell death necessary for the regulation of the
      size of organs in adult life. Disruption of apoptotic pathways has been suggested
      as an important regulatory mechanism in prostatic tumours. The aim of this study
      was to examine the expression of apoptosis-regulating genes bcl-2 and p53 using
      immunohistochemistry, and the Gleason score in core needle biopsy specimens of
      prostate adenocarcinoma. We studied bcl-2 and p53 expression in 30 cases of low-,
      30 cases of intermediate- and 20 cases of high-grade prostate adenocarcinoma.
      Overexpression of bcl-2 and p53 were noted in 54 and 61 of 80 patients (67.5 and
      76.25%), respectively. The statistical analysis of the present data suggested
      that there is significant relation between p53 and bcl-2 expression, and Gleason
      score in prostate cancer. Thus, immunohistochemistry is a useful investigative
      parameter in assessing apoptosis to analyse the prognosis of prostatic tumours.

PMID- 22993554
TI  - Expression and tissue distribution of human X-linked armadillo repeat containing
      6.
AB  - The armadillo family of proteins has been implicated in embryogenesis and
      tumorigenesis. Armadillo repeat containing X-linked (ARMCX)1-6 and its most
      closely related protein, ARMC10, share an uncharacterized domain in their
      carboxyl-terminal region and thereby constitute a unique subfamily. We previously
      detected an elevated ARMCX6 mRNA level in human cervical carcinoma (HeLa) cells
      in which the cyclin-dependent kinase inhibitor 2A products (p16INK4A and p14ARF)
      were silenced by RNA interference; however, the function of the ARMCX6 gene has
      yet to be determined. In the present study, we demonstrated that ARMCX6 tagged
      with green fluorescent protein was localized in the cytoplasm of HeLa cells.
      ARMCX6 mRNA was highly detected in the pancreas and spleen, indicating a tissue
      specific expression pattern in human tissues. Taken together, these results
      suggest that ARMCX6 may be uniquely involved in a specific cellular function of
      certain tissues.

PMID- 22993555
TI  - Medicinal mushroom Phellinus linteus as an alternative cancer therapy.
AB  - Alternative cancer treatment with nutritional/dietary supplements containing a
      wide variety of herbal products is on the rise in Western countries. Recent
      epidemiological studies have suggested that mushrooms may prevent against
      different types of cancers. Phellinus linteus is a well-known Oriental medicinal
      fungus with a variety of biological activities, including immunomodulatory or
      direct antitumor activities. The activity of P. linteus and its extracts is
      associated with the presence of polysaccharides, their peptide/protein complexes
      and other low molecular weight complexes. Polysaccharide fractions isolated from
      P. linteus were found to be related to the increased activity of immune cells
      such as the production of cytokines by macrophages and B-cells or the increased
      cytotoxic activity of natural killer cells. Moreover, P. linteus was found to
      modulate the expression or activity of various genes involved in cell
      proliferation, apoptosis, angiogenesis, invasive behavior and chemoprevention.
      Finally, P. linteus extracts demonstrated tumor regression in three independent
      case reports, suggesting that an extract from P. linteus or a dietary supplement
      based on the extract from P. linteus may have potential use for the alternative
      treatment of cancer.

PMID- 22993556
TI  - Tubulin alpha-6 chain is a stably expressed reference gene in archival samples of
      normal oral tissue and oral squamous cell carcinoma.
AB  - One of the most critical factors in gene expression studies using quantitative
      real-time PCR is the choice of reference gene. Many of the commonly used
      reference genes have been shown to vary during a number of biological processes
      as well as between tissues. It is therefore important to always verify the
      stability of the gene of choice for all new tissues and experimental conditions.
      Here, we used two publicly available computer software packages (GeNorm and
      NormFinder) to investigate the stability of eight potential reference genes in
      formalin-fixed paraffin-embedded (FFPE) samples from normal oral tissue of
      different origin as well as from oral squamous cell carcinomas. Both programs
      found the tubulin alpha-6 chain (TUBA6) and ribosomal protein S13 (RPS13) to have
      the most stable expression between malignant and non-malignant tissue. NormFinder
      also found TUBA6 to be the most stable gene when samples were grouped according
      to tissue origin. FFPE samples constitute a large research resource, which
      considerably increases the number of samples available for analysis, leading to
      more reliable conclusions. Verification of a proper reference gene in oral FFPE
      tissue is therefore of great importance for future studies.

PMID- 22993557
TI  - Clinical and immunological assessment in breast cancer patients receiving
      anticancer therapy and bovine dialyzable leukocyte extract as an adjuvant.
AB  - Dialyzable leukocyte extract (DLE) is one of the immunological agents used as an
      adjuvant in cancer therapy; it has been associated with improved quality of life
      during cancer chemotherapy. Based on these previous findings and on the observed
      clinical benefits attributed to DLE in other types of cancer, we investigated its
      clinical and immunological effects as a therapy adjuvant on breast cancer
      patients who received only chemotherapy, as compared to patients administered
      bovine DLE (bDLE) as an adjuvant. This study included 43 breast cancer patients
      who were about to begin chemotherapy. This group was divided as follows: 25
      received chemotherapy and bDLE as an adjuvant therapy, and 18 received only
      chemotherapy without the adjuvant. All patient clinical and immunological
      responses were monitored. Among patients in the group that received bDLE as
      adjuvant, 60% showed a complete response, 32% showed a partial response and 8%
      did not respond. By contrast, in the group without the adjuvant, 39% showed a
      complete response, 50% displayed a partial response and 11% were non-responders.
      In addition, bDLE treatment in combination with chemotherapy resulted in the
      enhancement of the Karnofsky performance scale during chemotherapy. Even though
      patients underwent several cycles of chemotherapy without bDLE, the lymphocyte
      population dropped to below the reference value. On the other hand, in patients
      with bDLE as adjuvant, the CD4(+) and CD8(+) lymphocytes and the B lymphocytes
      were maintained within the median range of the reference value. The number of
      natural killer cells also increased after chemotherapy treatment with bDLE as an
      adjuvant. In conclusion, bDLE treatment contributes to significant immunological
      recovery in patients that have undergone heavy chemotherapy, increasing the
      clinical response and quality of life during chemotherapy.

PMID- 22993558
TI  - Infective endocarditis associated with acute renal failure: Repeat renal biopsy
      and successful recovery.
AB  - Infective endocarditis (IE) is a serious disease with a high associated mortality
      rate, particularly when complicated by acute renal failure (ARF). Although valve
      surgery and treatment with antibiotic agents are recommended, surgical options
      and the optimal therapy are not as yet well documented. Here, we report a rare
      case of IE in a young man with a history of intravenous drug abuse, who presented
      with high fever, bilateral thoracalgia, lower limb edema and renal dysfunction.
      After treatment with antibiotics, hemodialysis and anticoagulants, a tricuspid
      valve replacement surgery was performed on the patient. After surgery, his renal
      functions deteriorated and progressed to ARF. The first renal biopsy showed type
      II crescentic glomerulonephritis. After receiving continuous ambulatory
      peritoneal dialysis followed by administration of an angiotensin converting
      enzyme inhibitor and angiotensin receptor blockers, the patient's serum
      creatinine level decreased and the urine output increased gradually. In order to
      identify the renal turnover, we performed a second biopsy and found significant
      improvement in the pathological changes with endocapillary proliferative
      glomerulonephritis and fibrous crescents. Successful recovery of renal function
      was achieved 12 weeks after the initiation of therapy. Therefore, eradication of
      infection, tricuspid valve replacement and renal substitution therapy may be
      sufficient in some cases.

PMID- 22993559
TI  - Expression of beta-catenin and REG Ialpha in relation to cell proliferative
      ability in salivary gland tumors.
AB  - beta-catenin and its target gene products have been thought to play pivotal roles
      in the progression of various neoplasias. In the present study, we examined the
      expression of beta-catenin and regenerating gene (REG) Ialpha in salivary gland
      tumors and investigated its relationship to their cell proliferative ability.
      Nineteen patients with pleomorphic adenoma (PA) and 17 patients with malignant
      salivary gland tumors, including 7 adenoid cystic carcinomas, 7 mucoepidermoid
      carcinomas and 3 polymorphous low-grade adenocarcinomas, were enrolled. The
      specimens that had been surgically resected from these patients were examined
      using immunohistochemistry for beta-catenin, REG Ialpha and Ki67. The
      relationships between clinicopathological features and beta-catenin or REG Ialpha
      expression were then analyzed. beta-catenin immunoreactivity was positive in 14
      PAs (73.3%) and 14 malignant salivary gland tumors (82.4%). Four (28.6%) of the
      14 beta-catenin-positive PAs showed clear beta-catenin immunoreactivity at the
      plasma membrane (membrane type), while 10 (71.4%) showed diffuse immunoreactivity
      in the cytoplasm and nucleus but not at the plasma membrane (non-membrane type).
      Twelve (85.9%) of the 14 malignant salivary gland tumors showed non-membrane-type
      beta-catenin expression. Six (31.6%) of the 19 PAs and 10 (58.8%) of the 17
      malignant salivary gland tumors were positive for REG Ialpha expression. PAs with
      non-membrane-type beta-catenin expression showed a significantly higher Ki67
      labeling index than PAs with negative or membrane-type expression. Additionally,
      PAs that were REG Ialpha-positive showed a significantly higher Ki67 labeling
      index than those that were negative. Non-membrane-type beta-catenin expression
      was related to REG Ialpha positivity in PA lesions. beta-catenin and its
      associated REG Ialpha protein may play a role as growth-promoting factors in the
      development of salivary gland tumors.

PMID- 22993561
TI  - Extra-nodal natural killer/T cell lymphoma, nasal-type, treated by concurrent
      chemoradiotherapy.
AB  - The present study reports on a case of extra-nodal natural killer/T cell
      lymphoma, nasal-type (ENKL), stage IIEA, in a 50-year-old woman who presented
      with a white tumor on a refractory ulcer on the gum. Concurrent chemoradiotherapy
      was administered, and effected a partial response. However, tumor recurrence was
      observed 5 months after the final diagnosis, and the patient succumbed 1 month
      after recurrence. Although a definitive treatment for ENKL has yet to be
      established due to its rarity, radiation therapy (RT) is crucial to therapy, as
      ENKL is very sensitive to RT. However, treatment with radiation levels above 50
      Gy with an extended RT field are required for a favorable outcome. The
      development of novel chemotherapy regimens may therefore be useful. Additionally,
      autologous or allogenic hematopoietic stem-cell transplantation may prove to be a
      promising approach.

PMID- 22993560
TI  - Expression of ERCC1 and class III beta-tubulin is associated with the survival of
      resected stage III non-small cell lung cancer patients treated with induction
      chemoradiotherapy using carboplatin-taxane.
AB  - Several molecules have been proven to be associated with responsiveness to
      chemotherapy. A clinical study on the expression of excision repair cross
      complementing (ERCC)-1 and class III beta-tubulin was conducted in advanced stage
      non-small cell lung cancer (NSCLC) patients. We investigated 34 resected stage
      III NSCLC patients treated with induction chemoradiotherapy using carboplatin
      taxane. Immunohistochemistry was performed to evaluate the intratumoral
      expression of ERCC1 and class III beta-tubulin. Nineteen tumors (55.9%) were
      ERCC1-high and 11 (32.4%) were class III beta-tubulin-high. There was no
      correlation between ERCC1 and class III beta-tubulin expression (r=0.208).
      Regarding the pathological effect of induction therapy, the percentage of ERCC1
      positive tumor cells was lower in tumors with a major response than in tumors
      with a minor response (P=0.0851). The percentage of class III beta-tubulin
      positive tumor cells was significantly lower in tumors with a major response than
      in tumors with a minor response (P=0.0105). Regarding patient survival, the
      overall survival was significantly higher in patients with ERCC1-low tumors than
      in those with ERCC1-high tumors (P=0.0034). The overall survival was also
      significantly higher in patients with class III beta-tubulin-low tumors than in
      those with class III beta-tubulin-high tumors (P=0.0185). Cox regression analysis
      also demonstrated that ERCC1 (P=0.0467) and class III beta-tubulin statuses
      (P=0.0237) were significant prognostic factors. Co-evaluations of the
      intratumoral expression of ERCC1 and class III beta-tubulin are clinically useful
      for identifying patient populations responsive to chemotherapy using carboplatin
      taxane.

PMID- 22993562
TI  - Dynamic changes in E-cadherin gene promoter methylation during metastatic
      progression in papillary thyroid cancer.
AB  - Thyroid cancer cells undergo epithelial to mesenchymal transition (EMT) in the
      invasive front of tumor. To determine whether the mesenchymal feature of invasive
      cancer cells is maintained in metastatic sites, we examined E-cadherin
      methylation and E-cadherin expression in 66 papillary thyroid cancer (PTC)
      samples and in 34 corresponding lymph node metastases (LNM). Relationships
      between E-cadherin and cell motility were evaluated using thyroid cancer cell
      lines. Hypermethylation of the E-cadherin gene promoter was detected in 39.3% of
      the PTCs, and loss of E-cadherin expression correlated with lymphocytic
      infiltration, extrathyroidal invasion and the presence of metastases. Comparing
      primary PTCs to the corresponding LNM, E-cadherin methylation status was
      identical in 60% of the cases. The switch in E-cadherin promoter status from
      unmethylated in PTCs to hypermethylated in LNM was detected in 5%; and from
      hypermethylatated in PTCs to unmethylated in LNM in 35%. Loss of epigenetic
      silencing in LNM was associated with a gain of E-cadherin expression.
      Hypermethylation of the E-cadherin gene promoter was detected in thyroid cancer
      cell lines with mesenchymal-like morphology. Loss of E-cadherin expression in
      these cells correlated with high migratory ability. Inhibition of RAS/ERK or
      PI3K/AKT signaling decreased the migratory ability of these cells but did not
      induce E-cadherin expression. In the cells with epithelial-like morphology,
      treatments with phorbol-ester or tumor necrosis factor (TNF)-alpha resulted in
      translocation of membranous E-cadherin to the cytoplasm and induction of
      migration. E-cadherin promoter methylation status and E-cadherin expression were
      not affected by TNF. Demethylating agents induced apoptosis in the mesenchymal
      like cells but had no effect on E-cadherin expression or on migratory ability.
      Together, dynamic changes in E-cadherin methylation occur during metastatic
      progression in thyroid cancer. Epigenetic mechanisms and TNF-inducible signaling
      independently contribute to the regulation of E-cadherin expression and
      localization. These mechanisms may play a role in the induction of EMT in primary
      tumors and in the conversion from the mesenchymal to the epithelial phenotype in
      metastases.

PMID- 22993563
TI  - Proliferation of human lung cancer in an orthotopic transplantation mouse model.
AB  - The objective of this study was to clarify the growth and proliferation style of
      human lung cancer grown in an orthotopic transplantation model. The human lung
      squamous cell carcinoma SQ5 and adenocarcinoma A549 cell lines were used. Tumor
      cells suspended in serum-free medium were directly injected into the main bronchi
      of anesthetized female Balb/c athymic nude mice with simultaneous administration
      of 0.01 M ethylenediaminetetraacetic acid. Bromodeoxyuridine was injected into
      mice 20 min before sacrifice. Lung tissue with tumor nodules and subcutaneous
      tumors were fixed and confirmed by histological examinations. Bromodeoxyuridine
      labeled cells in the tumor area were counted, and the proliferation index was
      calculated. Lung tumor colonies of various sizes were obtained in the SQ5- and
      A549-cell orthotopically transplanted mice. Orthotopic SQ5 tumors whose minor
      diameter was 40-700 MUm and major diameter was 80-830 MUm showed no definite
      necrosis. Orthotopic SQ5 tumors whose minor diameter was 540-5,200 MUm and major
      diameter was 600-6,100 MUm showed definite necrosis in the tumor center. Similar
      results were also found in the orthotopic A549 tumors. The proliferation index
      was 7.38 (3.03)/10.63 (3.10) in the orthotopic SQ5 tumors with/without necrosis
      and 6.99 (2.10) in the subcutaneous SQ5 tumors with necrosis, respectively. The
      proliferation index was 2.70 (0.88)/3.53 (1.70) in the orthotopic A549 tumors
      with/without necrosis and 3.91 (0.63) in the subcutaneous A549 tumors with
      necrosis, respectively. The data suggest that this orthotopic transplantation
      model may provide the proper organ microenvironment for lung cancer growth and
      may be suitable for the target therapy research of human lung cancer.

PMID- 22993564
TI  - Consultation clinics for complementary and alternative medicine at Japanese
      university hospitals: An analysis at Tokushima University Hospital.
AB  - Here, we report on a Consultation Clinic for Complementary and Alternative
      Medicine (CAM) which we established at Tokushima University Hospital in July of
      2007 with the aim of providing person-to-person information on CAM, though not
      CAM therapy itself. In December of 2008, we received 55 applications for
      consultation, 37% concerning health foods, 37% Japanese herbal medicine (Kampo),
      and 26% various other topics. The consultants (nutritionists and pharmacists)
      communicated individually with 38 applicants; malignancies (26%) and
      cardiovascular disease (24%) were the main underlying concerns. To promote the
      quality of consultation, data was collected by means of focus group interviews
      concerning the perspective of the consultants. Safe and effective use of CAM
      requires a network of communication linking individuals, consultation teams,
      physicians, primary care institutions and university hospitals. To advance this
      goal, we plan to broaden the efforts described herein. Our findings indicate that
      the specific role of the consultation clinic in promoting the scientific use of
      CAM merits further study.

PMID- 22993566
TI  - Correlation of granulin expression in intracranial meningiomas to clinical
      parameters.
AB  - The granulins, a novel class of peptides from leukocytes, are growth factors that
      mediate cycle progression and the motility of epithelial and mesenchymal cells.
      They are also involved in tissue repair and tumorigenesis. We investigated
      granulin expression in intracranial meningiomas by reverse transcription
      polymerase chain reaction and correlated its expression to clinical parameters.
      Seventy-nine patients who underwent tumor removal for intracranial meningiomas
      were included in this study. Granulin expression was analyzed in respect to
      clinical parameters including age, gender, tumor size and peritumoral brain edema
      (PTBE). Granulin was expressed in the tumors of 29 of 79 (36.7%) patients with
      intracranial meningiomas, and its presence or absence was correlated to tumor
      size and PTBE volume. However, granulin expression did not vary significantly
      according to patient age or gender. Our data provide improved understanding about
      the clinical implications of granulin expression in intracranial meningiomas.
      Additionally, our information suggests a potential role for granulin as a
      molecular target in the management of meningiomas.

PMID- 22993565
TI  - Effects of pre-operative transcatheter arterial chemoembolization for resectable
      hepatocellular carcinoma: Implication of circulating cancer cells by detection of
      alpha-fetoprotein mRNA.
AB  - Transcatheter arterial chemoembolization (TACE) is useful for the treatment of
      multiple hepatocellular carcinomas (HCCs). Pre-operative TACE is used to reduce
      recurrence caused by peri- and post-operative spread of cancer cells; however,
      the efficacy is controversial. In this study, we evaluated the efficacy of pre
      operative TACE for HCC and the implication of circulating cancer cells,
      retrospectively. We analyzed 495 patients with HCC who had undergone hepatectomy
      between 1980 and 2006, including 252 patients (50.9%) who received pre-operative
      TACE. The median follow-up period was 49.9 months. We compared the survival of
      TACE and non-TACE groups and also performed subgroup analysis. alpha-fetoprotein
      (AFP) mRNA was quantified to represent circulating cancer cells. Pre-operative
      TACE prolonged disease-free survival after hepatectomy in patients with HCCs
      greater than 5 cm (5-year disease-free survival of the pre-operative TACE and no
      TACE groups was 37.3 vs. 14.8%, p<0.05). Patients with tumors showing 70% or
      greater necrosis had a significantly more favorable survival, and those with
      complete necrosis were all AFP mRNA-negative. The survival of the AFP mRNA
      positive patients was worse than that of the AFP mRNA-negative patients. Pre
      operative TACE may be beneficial for patients with tumors larger than 5 cm, and
      AFP mRNA quantification may be useful for the prediction of survival after
      surgery in TACE-treated patients.

PMID- 22993567
TI  - CD318/CUB-domain-containing protein 1 expression on cord blood hematopoietic
      progenitors.
AB  - CUB-domain-containing protein 1 (CDCP1)/CD318 is a single transmembrane molecule
      highly expressed in colorectal cancer and leukemia. It has also been shown to be
      expressed in hematopoietic progenitor cells. In this study, we analyzed the
      expression of CD318 on cord blood hematopoietic stem and progenitor cells. Cord
      blood mononuclear cells were depleted of mature blood cell linage (Lin)-positive
      cells and then Lin-negative cells were sorted by flow cytometry based on the
      expression of CD34 and CD318. Analysis of sorted cells by colony-forming assay
      showed that CD34(+)CD318(+) cells produced more mixed colony forming units and
      erythroid burst forming unit-derived colonies than CD34(+)CD318(-) cells. These
      colonies were also produced by CD34(-)CD318(+) and CD34(-)CD318(-) cells, but
      were generally fewer in number. When sorted cells were cultured on a monolayer of
      human mesenchymal stem cells, CD34(+)CD318(+) cells proliferated more abundantly
      than CD34(+)CD318(-) cells, while CD34(-)CD318(+) and CD34(-)CD318(-) cells
      failed to proliferate. Transplantation of CD34(+)CD318(+) cells into non-obese
      diabetic/severe combined immunodeficient disease (NOD/SCID) mice resulted in
      efficient reconstitution of human cells, indicating that CD34(+)CD318(+) cells
      possess strong SCID-repopulating cell activity. These findings suggest that the
      co-expression of CD34 and CD318 identifies the immature character of
      hematopoietic stem cells.

PMID- 22993568
TI  - Evaluation of serum iron levels during FOLFOX4 and FOLFIRI therapies.
AB  - FOLFOX4 and FOLFIRI are effective regimens for the treatment of advanced
      colorectal cancer, and their use together with molecular targeting drugs has
      recently become more common. In the present study, we evaluated the changes in
      the serum iron levels of patients undergoing FOLFOX4 or FOLFIRI therapy alone or
      in combination with bevacizumab (BV). The serum iron level was increased 48 h
      after therapy and was restored to baseline 2 weeks afterwards in colorectal
      cancer patients who received FOLFOX4 or FOLFIRI alone or in combination with BV.
      This transient increase in serum iron was observed repeatedly during
      chemotherapy. The serum iron level was 71.66+/-28.96 MUg/dl (mean +/- standard
      deviation) before treatment and significantly increased to 186.82+/-83.17 MUg/dl
      (p<0.001) 48 h after therapy. A transient increase in serum iron levels was also
      observed when FOLFIRI was administered to a patient after tumor resection. In
      contrast, no decrease in blood hemoglobin, no increase in liver enzymes and no
      increase in urinary iron excretion were observed. Based on these results, it can
      be concluded that an increase in serum iron may be induced by a transient change
      in iron distribution within the body after FOLFOX4/FOLFIRI therapy with or
      without BV.

PMID- 22993569
TI  - Potentiation of the growth inhibition activity of 2-({4-[4-(acridin-9
      ylamino)phenylthio]phenyl}(2-hydroxyethyl)amino)ethan-1-ol (CK0402) by Herceptin
      in SKBR-3 human breast cancer cells.
AB  - The 9-aminoacridine derivative, 2-({4-[4-(acridin-9-ylamino)phenylthio]phenyl}(2
      hydroxyethyl) amino)ethan-1-ol (CK0402) was selected as a potential anticancer
      agent among a series of sulfur-containing 9-aminoacridine analogues. CK0402 is a
      topoisomerase II inhibitor and has been shown to exert impressive anticancer
      activities in both in vitro and in vivo assays. In the present study, we tested
      the effects of CK0402 in a panel of established human breast cancer cells with
      varying ER and HER2/neu status. The ER(-) and HER2-overexpressing SKBR-3 cells
      were the most sensitive cells tested in growth inhibition to CK0402 treatment,
      and the growth inhibition was in a time-and concentration-dependent manner. In
      addition, CK0402 also induced stronger G(2)/M arrest, apoptosis and autophagy in
      SKBR-3 cells than in ER(+) and HER2(-) MCF-7 cells. To the best of our knowledge,
      CK0402 is the first 9-aminoacridine analogue to induce autophagy. These findings
      suggest that CK0402 may be effective against the more aggressive and malignant
      ER(-) and HER2-overexpressing breast cancer. Towards this end, we further
      demonstrated that the combination of CK0402 and Herceptin exhibited
      synergistic/additive cytotoxic effects in SKBR-3 cells using the median
      effect/combination-index isobologram methodology (CI value). Our results indicate
      that the combination of CK0402 and Herceptin may be a potential therapeutic
      option against the more aggressive ER(-) and HER2-overexpressing breast cancer.

PMID- 22993570
TI  - Epigenetic activation of E-cadherin is a candidate therapeutic target in human
      hepatocellular carcinoma.
AB  - E-cadherin is a key cell adhesion molecule implicated in tumor suppression that
      is frequently altered in hepatocellular carcinoma (HCC), particularly in
      hepatitis B virus-related tumors. Here, we report that the epigenetic drugs 5
      azacytidine and trichostatin A up-regulated E-cadherin expression in HCC cells.
      The depletion of DNMT1 restored E-cadherin expression via demethylation, whereas
      the depletion of DNMT3A or DNMT3B did not. Activated E-cadherin suppressed HCC
      cell colony formation. However, E-cadherin expression was repressed by HBx
      transfection due to the DNA methylation induced by the elevation of DNMT1 in the
      HCC cell lines. The present study indicates that E-cadherin expression is
      regulated by epigenetic agents in HCC cells, which suggests a schema for
      restoring E-cadherin by targeting its epigenetic mechanism.

PMID- 22993571
TI  - Impact of human papillomavirus genotype on response to treatment and survival in
      patients receiving radiotherapy for squamous cell carcinoma of the cervix.
AB  - To determine the clinical implications and prognostic value of the human
      papillomavirus (HPV) genotype, we evaluated the various HPV types in patients
      receiving radiotherapy for squamous cell carcinoma of the cervix. The study
      population included 113 invasive squamous cell carcinoma patients treated with
      radiation or chemoradiation between 1993 and 2002. The median age of the patients
      was 61 years. Tumors were classified by the International Federation of
      Gynecology and Obstetrics staging as stage IB in 11 patients, stage II in 39,
      stage III in 57 and stage IVA in 6 patients. To investigate HPV infection and its
      genotypes in the tumor specimens, L1 consensus PCR was performed followed by the
      direct nucleotide sequencing of the PCR products. Ninety-five samples (84.1%)
      were positive for HPV DNA. The most prevalent type was HPV-16 (34.7%). Poorer
      response to radiotherapy was observed in the patients with the HPV-16 genotype,
      in which 7 of the 33 patients had persistent disease. Only 1 of the 10 patients
      with HPV-58, 1 of the 5 with HPV-31 and 5 of the 10 patients with HPV-33 had a
      recurrence. The 5-year survival rate was 90, 80, 69.4 and 39% in the HPV-58, HPV
      31, HPV-16 and HPV-33 type groups, respectively. Patients with HPV-31 and HPV-58
      types were found to have better survival, whereas patients with the HPV-33 type
      experienced a higher risk of death. HPV genotyping may serve as a potential
      biomarker of response to radiation and prognosis in cervical carcinoma patients
      undergoing radio- or chemoradiotherapy.

PMID- 22993572
TI  - Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.
AB  - The aim of the present study was to identify the possible mechanisms by which
      certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to
      treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production.
      To this end, we compared the proliferative effects on mammary cancer cells of the
      novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and
      evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the
      cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In
      ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation
      stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated
      proliferation by an alpha-fetoprotein-derived cyclic nonapeptide. The effects
      reported herein may be extrapolated to infiltrating mammary cancer, where the
      activity of local macrophages may stimulate tumor growth. We suggest that
      increased breast cancer growth in obese patients may be related to increased
      27OHC circulatory levels.

PMID- 22993573
TI  - Improving gene transfer in human renal carcinoma cells: Utilization of adenovirus
      vectors containing chimeric type 5 and type 35 fiber proteins.
AB  - The transduction efficacy of adenovirus serotype 5 (Ad5) vector in human renal
      carcinoma cells is generally low due to the down-regulated expression of
      Coxsackie and adenovirus receptor (CAR) in target cells. By contrast, the
      infectivity of adenovirus serotype 35 vectors depends on the binding rate to CD46
      receptor, independent of CAR. In this study, we examined whether an adenovirus
      vector containing chimeric type 5 and type 35 fiber proteins (Ad5/F35) increases
      transduction efficiency compared to Ad5 vector in human renal carcinoma cells in
      vitro. The expression of CAR was much lower in the human renal carcinoma cells
      than in control HEK293 cells. By contrast, the expression of CD46 was similar and
      perhaps at a higher level in the human renal carcinoma cells than in the HEK293
      cells. The transduction efficacy of Ad5/F35 vector was dramatically higher
      compared to that of Ad5 in human renal carcinoma cells, and was correlated to the
      expression of CD46. Thus, Ad5/35 vector may be useful for the development of
      novel gene therapy approaches to renal cell carcinoma.

PMID- 22993574
TI  - Myofibroblasts are associated with the progression of scirrhous gastric
      carcinoma.
AB  - Fibroblasts, particularly myofibroblasts, affect the malignant progression of
      cancer cells in vitro. However, to date few reports have addressed the clinical
      significance of myofibroblasts in the gastric cancer microenvironment. This study
      examined the correlation between myofibroblast expression and clinicopathological
      features in gastric carcinoma. A total of 265 primary gastric tumors resected by
      gastrectomy were stained with antibodies against alpha-smooth muscle actin and
      vimentin. Stromal cells positive for vimentin were considered to be fibroblasts.
      Myofibroblasts were defined as fibroblasts positive for alpha-smooth muscle
      staining. Myofibroblast-positive gastric carcinoma was established when
      myofibroblasts accounted for more than 25% of fibroblasts in the cancer stroma.
      Myofibroblast expression was positive in 92 (35%) of the 265 gastric carcinomas.
      Myofibroblast expression showed a significantly (p<0.001) high frequency in
      advanced gastric cancers (76 of 146), in comparison to the early stage cancers
      (16 of 119). Taken together, there was a statistically significant correlation
      between myofibroblast expression and scirrhous type gastric cancer (p<0.001),
      lymph node metastasis (p<0.001), lymphatic invasion (p<0.001) and peritoneal
      dissemination (p=0.005). The prognosis of patients with tumors positive for
      myofibroblast expression was significantly (p<0.001) worse, while a multivariate
      analysis revealed that myofibroblast expression was not an independent prognostic
      factor. These findings suggest that myofibroblasts are associated with scirrhous
      gastric cancer. Overexpression of myofibroblasts may therefore be a useful
      prognostic indicator of gastric carcinoma.

PMID- 22993575
TI  - Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model.
AB  - Radiotherapy is successfully used to treat neoplastic lesions, but may adversely
      affect normal tissues within the irradiated volume. However, additional clinical
      and para-clinical data are required for a comprehensive understanding of the
      pathogenesis of this damage. We assessed a rat model using clinical records and
      medical imaging to gain a better understanding of irradiation-induced tissue
      damage. The hindlimbs of the rats in this model were irradiated with a single
      dose of 30 or 50 Gy. Sequential analysis was based on observation records of
      stage and planar scintigraphy. Additional radiography, radiohistology and
      histology studies were performed to detect histological alterations. All animals
      developed acute and late effects, with an increased severity after a dose of 50
      Gy. The bone uptake of (99m)Tc-HDP was significantly decreased in a dose- and
      time-dependent manner. Histologically, significant tissue damage was observed.
      After the 50 Gy irradiation, the animals developed lesions characteristic of
      osteoradionecrosis (ORN). Radiographic and histological studies provided evidence
      of lytic bone lesions. Our rat model developed tissue damage characteristic of
      radiation injury after a single 30 Gy irradiation and tissue degeneration similar
      to that which occurs during human ORN after a 50 Gy irradiation. The development
      of this animal model is an essential step in exploring the pathogenesis of
      irradiation-induced tissue damage, and may be used to test the efficacy of new
      treatments.

PMID- 22993576
TI  - Immunohistochemical assessment of primary breast tumors and metachronous brain
      metastases, with particular regard to differences in the expression of biological
      markers and prognosis.
AB  - In this study, we conducted an immunohistochemical analysis of primary breast
      tumors and metachronous brain metastases to compare the differences in the
      expression of biological markers between the two. Carcinoma tissues from primary
      breast tumors and metachronous brain metastases collected from 21 patients were
      examined immunohistochemically for the expression status of the estrogen receptor
      (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER)
      2, Ki-67, bcl-2 and p53, and the results were compared. In addition, the
      relationships between the expression of these factors and prognosis were
      evaluated. There were no significant differences in the frequencies of ER-, PgR-,
      HER-2-, bcl-2- or p53-positivity between the primary breast tumors and
      metachronous brain metastases. While the Ki-67 labeling index (LI) was high in
      both the primary breast tumors and brain metastases, it was significantly higher
      in the brain metastases than in the corresponding primary breast tumors
      (P=0.003). With regard to the prognosis, breast cancer patients who showed ER
      positivity in the primary tumors showed significantly longer survival after
      primary diagnosis (P=0.0076). Furthermore, breast cancer patients who exhibited
      ER-positivity, bcl-2-positivity or p53-negativity in the primary tumors showed
      significantly longer intervals from primary diagnosis to the detection of the
      brain metastases. Of all the markers, only the Ki-67 LI was significantly higher
      in the brain metastases than in the primary breast tumors. We confirmed that the
      tumor characteristics were worse in the metachronous brain metastases.

PMID- 22993577
TI  - Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract:
      Case report and in vitro study.
AB  - Malignant melanoma (MM) is an aggressive chemoresistant skin cancer characterized
      by rapid metastasis and a poor prognosis. Therefore, the development of
      innovative effective therapies is critical. MK615 is an extract from the Japanese
      apricot Prunus mume Sieb. Et Zucc (Ume). At a neutral pH, it contains natural
      chemical substances such as triterpenoids that exert anti-neoplastic effects in
      several types of cancers. We found that in patients with advanced MM, MK615
      dramatically suppressed the cutaneous in-transit metastasis of the disease. Pre-
      and post-treatment comparison of tumors showed that the apoptotic index was
      significantly increased by MK615. In vitro studies, MTT assay, flow cytometric
      cell cycle analysis and immunofluorescence microscopy revealed that MK615
      inhibited the growth of SK-MEL28 cells in a dose-dependent manner, increased the
      proportion of cells in sub-G1 phase and induced apoptosis. We further examined
      the expression of the receptor for advanced glycation end products (RAGE). RAGE
      is a multi-ligand receptor that binds to a novel cytokine, high mobility group
      box protein 1 (HMGB1), as well as advanced glycation end products. There is
      evidence that RAGE/HMGB1 interactions enhance cell invasion in MM. Here, we
      present Western blotting and immunofluorescence microscopy data indicating that
      MK615 inhibited the expression of RAGE in SK-MEL28 cells, and suppressed the
      release of HMGB1 by SK-MEL28 cells. Our findings suggest that MK615 may be a
      valuable tool for treating MM and other malignant tumors.

PMID- 22993578
TI  - Bleeding diathesis is associated with an A15T heterozygous mutation in exon 2 of
      the plasminogen activator inhibitor type 1.
AB  - In the present study, we present a 60-year-old woman of American Indian descent
      with a life-long history of bleeding diathesis. She had a history of recurrent
      and prolonged bleeding such as mild epistaxis, gingival bleeding and microscopic
      hematurias. She also experienced a severe bleeding event after surgery. The
      patient had a large family with a history of a tendency of bleeding, severe in
      some cases. Hemostatic screening studies revealed no abnormalities, which could
      explain the bleeding tendency. Clot formation of sodium-citrated blood was
      analyzed by thromboelastography, which suggested a low platelet count or
      plasminogen activator inhibitor-1 (PAI-1) deficiency. However, her platelet count
      was slightly elevated. Subsequent sequencing of the PAI-1 gene revealed a
      heterozygous Ala15Thr mutation in the signal peptide. This type of deficiency is
      related to dynamics of PAI-1 secretion rather than its low levels or activity. We
      concluded that the PAI-1 mutation was likely the etiology of the bleeding
      diathesis in this patient.

PMID- 22993579
TI  - Rho-kinase regulates prostaglandin D(2)-stimulated heat shock protein 27
      induction in osteoblasts.
AB  - We previously reported that prostaglandin D(2) (PGD(2)) stimulates heat shock
      protein 27 (HSP27) induction through p44/p42 mitogen-activated protein (MAP)
      kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal
      kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In addition, we recently
      showed that PGD(2) activates Rho-kinase, resulting in the regulation of
      interleukin-6 synthesis via activation of p38 MAP kinase but not p44/p42 MAP
      kinase in these cells. In the present study, in order to investigate whether Rho
      kinase is involved in the PGD(2)-stimulated HSP27 induction in MC3T3-E1 cells, we
      examined the effects of Rho-kinase inhibitors on HSP27 induction. Y27632 and
      fasudil, Rho-kinase inhibitors, markedly suppressed the HSP27 induction
      stimulated by PGD(2) in a dose-dependent manner without affecting levels of HSP70
      in the presence of PGD(2). Immunofluorescence microscopy studies also revealed
      that Y27632 and fasudil markedly suppressed the induction of HSP27. Y27632 and
      fasudil attenuated the PGD(2)-induced phosphorylation levels of SAPK/JNK. In
      conclusion, Rho-kinase inhibitors regulate PGD(2)-stimulated HSP27 induction via
      activation of both SAPK/JNK and p38 MAP kinase in osteoblasts.

PMID- 22993580
TI  - Alteration of extracellular superoxide dismutase expression is associated with an
      aggressive phenotype of oral squamous-cell carcinoma.
AB  - Oxidative stress results in damage to cellular structures and has been linked to
      numerous diseases, including cancer. Extracellular superoxide dismutase (EC-SOD)
      is a principal enzymatic antioxidant in extracellular space. The purpose of this
      study was to determine whether the expression of EC-SOD protein is altered in the
      carcinogenetic process of oral squamous-cell carcinoma (OSCC).
      Immunohistochemical analysis was carried out in matched normal and tumour
      specimens collected from 58 OSCCs and 20 oral premalignant lesions (OPLs).
      Correlations between the EC-SOD expression levels and clinicopathological
      features of OSCC patients were evaluated by Fisher's exact test. Although EC-SOD
      protein was consistently expressed on the plasma membrane of cells in normal
      tissues, plasma membranous EC-SOD expression was lost in almost all the OSCC
      specimens examined (98%). Instead, positive EC-SOD expression was detected in the
      cytoplasmic compartments of cancerous cells in both OPLs (65%) and OSCCs (52%),
      together with a high incidence of lymph node metastasis (p=0.0397). These results
      suggest that the dysregulation of EC-SOD protein expression is a frequently
      occuring and early event in oral carcinogenesis, and that cytoplasmic EC-SOD may
      contribute to the increased aggressiveness of OSCC.

PMID- 22993581
TI  - MEK inhibition suppresses cell invasion and migration in ovarian cancers with
      activation of ERK1/2.
AB  - The extracellular-regulated kinase (ERK) signaling pathway plays an important
      role in regulating the malignant potential of a cancer cell. However, the effect
      of ERK signaling on cancer metastasis is not clearly understood. In the present
      study, we examined the status of ERK activation in 88 ovarian carcinomas in order
      to clarify the clinicopathological and prognostic significance of phosphorylated
      ERK1/2 (p-ERK1/2). p-ERK1/2 expression was identified in 37 (42%) of 88 ovarian
      carcinomas. There was no significant correlation between p-ERK1/2 expression and
      any of the clinicopathological factors tested. No significant correlation between
      p-ERK1/2 expression and overall survival was found in patients with ovarian
      carcinoma treated with platinum and taxane chemotherapy (P=0.426). Next, to
      clarify the role of ERK1/2 activation in ovarian cancers, we inactivated ERK1/2
      in ovarian cancer cells using the MEK inhibitor, CI-1040, which prevents ERK1/2
      activation. Based on simulated wound healing and invasion chamber assays, we
      found that the motility and invasion of ES2 and MPSC1 cells with p-ERK1/2 were
      significantly reduced (P<0.01) after treatment with CI-1040. By contrast, CI-1040
      did not have any effect on KF28 cells, which were negative for p-ERK1/2. Twist
      was down-regulated simultaneously with p-ERK1/2 following treatment of ES2 and
      MPSC1 cells with CI-1040. Immunohistochemistry of ovarian carcinoma tissue
      revealed that the increased expression of p-ERK1/2 significantly correlated with
      Twist expression (P<0.01). The findings in this study provide new insight into
      the biological role of ERK signaling in ovarian carcinomas. Additionally, our
      observations have an important therapeutic implication for patients with ovarian
      cancers that express p-ERK1/2 as these patients may potentially benefit from CI
      1040 therapy.

PMID- 22993582
TI  - HER2/neu protein expression and fine needle breast aspiration from Argentinean
      patients with non-palpable breast lesions.
AB  - The objective of this pilot project was to investigate whether the breast fine
      needle aspiration (FNA) technique is a useful tool for determining the increased
      risk of breast cancer in patients with non-palpable breast lesions. FNA is a
      minimally invasive technique that isolates mammary epithelial cells from breast
      cells in the suspicious region. In this study, two FNA samples were collected
      from 12 patients. The level of HER2/neu expression at the mRNA level (in serum)
      was measured in each patient. As gene amplification is characteristic of cancer
      cells and may assist in diagnosis and prognostic assessment, it is crucial that
      gene amplification of HER2/neu in patients with non-palpable breast lesions is
      compared to breast biopsy results. In serum, the level of HER2/neu was determined
      by ELISA assay. Gene amplification was determined by PCR and confirmed by IHC
      employing monoclonal ERRB2 in the FNA sample. The results indicate that FNA has a
      good correlation with breast biopsy. FNA combined with mammographic imaging is a
      strong tool for determining favorable treatment options for patients.

PMID- 22993583
TI  - Correlation of obesity and osteoporosis: Effect of free fatty acids on bone
      marrow-derived mesenchymal stem cell differentiation.
AB  - Studies on the relationship between obesity and bone have recently become
      widespread. The aim of this study was to investigate the effect of obesity on
      bone, utilizing a diet-induced obese mouse model, and to explore the role of free
      fatty acids (FFAs) in the osteogenesis/adipogenesis of mouse bone marrow-derived
      mesenchymal stem cells (BMSCs). An obese mouse model was established by a high
      fat diet (HFD). Proximal femurs were collected at sacrifice, and bone mineral
      density (BMD) in the proximal femurs was measured by dual-energy X-ray
      absorptiometry. Bone histomorphometry was performed using undecalcified sections
      of the proximal femurs. The effect of obesity on the differentiation of mouse
      BMSCs was assessed by colony formation assays and gene expression analysis. In
      vitro, various osteogenic and adipogenic genes were determined by real-time
      quantitative PCR in mouse BMSCs after exposure to conditioned medium (CM) from
      FFA-treated 3T3-L1 adipocytes. Western blotting was further performed to analyze
      the representative protein expression of PPARgamma and Runx2. BMD and trabecular
      thickness were significantly greater in the HFD mice than in the control mice.
      CFU-osteo assay showed significantly increased osteogenesis of BMSCs. The mRNA
      level of Runx2 was significantly higher, while PPARgamma and Pref-1 were
      significantly lower in BMSCs from the HFD mice compared to the control mice. In
      mouse BMSCs, the Sox9 and Runx2 genes were significantly up-regulated after
      exposure to CM from FFA-treated adipocytes, while PPARgamma and CEBP-alpha were
      significantly down-regulated. Osteogenesis was significantly increased, while
      adipogenesis was significantly decreased. In conclusion, HFD-induced obesity may
      play a protective role in bone formation by concomitantly promoting osteogenic
      and suppressing adipogenic differentiation of BMSCs through factors secreted by
      FFA-treated adipocytes.

PMID- 22993584
TI  - Adjuvant FOLFOX-4 in patients with radically resected gastric cancer:
      Tolerability and prognostic factors.
AB  - The aim of the present study was to evaluate the toxicity and efficacy of the
      FOLFOX-4 regimen as adjuvant chemotherapy in patients with gastric cancer after
      radical surgery. Fifty-four patients (1 stage Ib, 6 stage II, 22 stage IIIa, 14
      stage IIIb and 11 stage IV) received 8-12 cycles of FOLFOX-4 (oxaliplatin 85
      mg/m(2), Day 1; leucovorin 100 mg/m(2) i.v., Days 1 and 2; 5-fluorouracil 400
      mg/m(2) i.v. bolus, Days 1 and 2 and 600 mg/m(2) in 22 h i.v. continuous
      infusion, Days 1 and 2; every 14 days). Toxicity was recorded at each cycle
      according to the National Cancer Institute Common Toxicity Criteria. Disease-free
      (DFS) and overall survival (OS) were calculated according to the Kaplan-Meier
      method. Thirty-eight patients (70.4%) completed the prescribed number of cycles
      of chemotherapy. The toxicity was mild. Grade 3-4 neutropenia occurred in 57% of
      patients, thrombocytopenia and anemia in 2% of cases. Peripheral neuropathy was
      experienced by 46% of the patients (grade 4 in 2% of cases). Five patients
      experienced grade 3 gastrointestinal toxicity. After a median follow-up of 33.1
      months, 17 patients relapsed and 17 succumbed to the disease. The mean observed
      DFS and OS were 49.7 months (range 40.7-58.8) and 57.9 months (range 49.6-66.2),
      respectively. At univariate analysis, females and patients who had received <8
      cycles of chemotherapy had a significantly worse probability of DFS and OS. The
      Cox model showed gender to be independent of the factors affecting DFS. Adjuvant
      FOLFOX-4 is feasible and well-tolerated in patients radically resected for
      gastric cancer. Receiving <4 months of adjuvant FOLFOX-4 could be detrimental to
      prognosis.

PMID- 22993585
TI  - Overexpression of endoglin (CD105) is associated with recurrence in radically
      resected gastric cancer.
AB  - The aim of this study was to examine the expression of endoglin (CD105) in
      resected gastric cancer and to evaluate the relationship between microvessel
      density (MVD) and tumor recurrence after surgery. One hundred and thirty-two
      patients who had undergone curative surgery for primary gastric cancer were
      immunohistochemically stained for CD105, and MVD was assessed based on the number
      of CD105-positive vessels. MMP-7 expression was also investigated to determine
      the relationship with MVD. High MVD was significantly correlated with worse
      relapse-free survival in all cases and stage I-II cases by log-rank test
      (p=0.0005 and p=0.0154, respectively). Furthermore, in stage I-II cases, high MVD
      was the only independent predictor for relapse-free survival by multivariate
      analysis of the Cox proportional hazard model [p=0.028; hazard ratio (HR)=4.582;
      95% confidence interval (CI) 1.184-17.737]. Regarding the specific patterns of
      recurrence, high MVD was independently related to locoregional recurrence
      [p=0.011; odds ratio (OR)=15.208; 95% CI 1.886-122.662] and hematogenous
      recurrence (p=0.002; OR=5.718; 95% CI 1.875-17.442) by multivariate logistic
      analysis. However, the expression of MMP-7 or CD105 combined with MVD was
      associated with relapse-free survival, although these prognostic impacts were not
      maintained in multivariate analysis. In conclusion, MVD recognized by CD105 may
      be useful as a predictor for the recurrence of resected gastric cancer and may
      have a specific association with the development of locoregional and hematogenous
      recurrence.

PMID- 22993586
TI  - Investigation of risk factors for prostate cancer patients with bone metastasis
      based on clinical data.
AB  - It has not yet been determined whether certain types of prostate cancer with bone
      metastasis (M1b PC) are associated with a poor outcome. The present study
      retrospectively assessed the potential significance of various clinical data in
      predicting the outcome of M1b PC. The subjects were 104 patients who attended our
      hospital and received a diagnosis of M1b PC between January 1998 and December
      2006. The age of the subjects ranged from 51 to 91 years (median 74). The
      observation period ranged from 4 to 122 months (median 43). The parameters
      investigated were T classification, N classification, Gleason score (GS), pre
      treatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade,
      alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium and hemoglobin
      (Hb) levels and platelet count. The 5-year cause-specific survival rate was 56.6%
      and the 10-year cause-specific survival rate was 34.9%. Log-rank test and Cox
      univariate analysis identified the following factors with statistically
      significant differences: pre-treatment PSA level >=192, N1, GS >=8, EOD grade
      3+4, high LDH, high ALP and low Hb. Multivariate Cox proportional hazard analysis
      identified the factors GS >=8 and high LDH with significant differences. The
      hazard ratio was 4.967 and 2.728, respectively, and the probability value (P) was
      0.029 and 0.004, respectively. When the subjects with GS >=8 and high LDH were
      classified as the high-risk group, the 5-year cause-specific survival rate was
      24.6%. The outcome was significantly poorer in this group (P<0.0001) than in the
      other group, which had a 5-year cause-specific survival rate of 67.7%. The
      present study showed that patients with M1b PC with GS >=8 and high LDH have a
      very poor outcome and thus should be treated as a high-risk group requiring close
      follow-up.

PMID- 22993587
TI  - Usefulness of intraoperative touch smear cytology in breast-conserving surgery.
AB  - In breast-conserving surgery, positive margins are closely related to
      intramammary recurrence, but methods of assessing resection stumps during breast
      conserving surgery have not been standardized. The present study investigated the
      usefulness of intraoperative touch smear cytology in our department. From 2005 to
      2008, a total of 420 patients underwent breast cancer surgery. Subjects comprised
      160 patients who underwent breast-conserving surgery and touch smear cytology.
      Results of the touch smear cytology were compared to those of the histological
      tissue analysis. Touch smear cytology displayed 70% sensitivity (14/20), 97.1%
      specificity (136/140) and a diagnostic accuracy of 93.8% (150/160). Six false
      negative cases and 4 false-positive cases were identified. Of the 6 false
      negatives, cancer cells were noted in the ductal component in 5 cases, and the
      degree of cancer cell atypia in the stump was low. Residual cancer cells were
      noted in the stump in 18 cases, and additional resection was performed in 16
      cases. Cancer cells were identified histologically in the additionally resected
      tissue in 8 of these 16 cases (50%). The direction of positive cytology was
      towards the nipple in 16 cases, lateral tissue in 5 cases and contralateral
      nipple in 2 cases. A greater cancer cell volume, as assessed by touch smear
      cytology, tended to be associated with higher frequency of positive margins, as
      assessed by histological tissue analysis. Touch smear cytology is easy to
      perform, offering a very useful technique yielding comparable results to
      histological tissue analysis.

PMID- 22993588
TI  - G2/M accumulation in prostate cancer cell line PC-3 is induced by Cdc25 inhibitor
      7-chloro-6-(2-morpholin-4-ylethylamino) quinoline-5, 8-dione (DA 3003-2).
AB  - Cdc25 phosphatases are dual-specific phosphatases that play a role in cell cycle
      progression. In many human cancers, Cdc25 phosphatases are overexpressed as
      compared with normal tissues. In addition, overexpression of Cdc25 phosphatases
      in prostate cancer is correlated with disease progression. The antiproliferative
      efficacy of Cdc25 phosphatase inhibitor 7-chloro-6-(2-morpholin-4-ylethylamino)
      quinoline-5, 8-dione (DA 3003-2) was investigated in the PC-3 asynchronous human
      prostate cancer cell line using a cell-based assay. The time course changes in
      cell cycle distribution and the modulation of cell cycle regulators after DA 3003
      2 administration were analyzed using the MTT assay. We found that the relative
      IC(50) of DA 3003-2 was 2-fold lower as compared with its congener (2
      mercaptoethanol)-3-methyl-1, 4-naphthoquinone (NSC 672121). Asynchronous PC-3
      cells accumulated in the G2/M phase at 24 h after treatment with 10 MUM DA 3003-2
      or 20 MUM NSC 672121, which represent IC(70) concentrations. Treatment of cells
      with DA 3003-2 caused hyperphosphorylation of Cdc2 tyr(15) in cyclin B(1) and
      cyclin A complexes. DA 3003-2 did not downregulate the protein expression levels
      of Cdc25s, cyclins and cyclin-dependent kinases (Cdks). To conclude, after DA
      3003-2 administration asynchronous PC-3 cells accumulated in the G2/M phase, with
      hyperphosphorylation of the G2/M cyclin-Cdk complex.

PMID- 22993589
TI  - Neoadjuvant intraarterial chemotherapy for stage IIB-IIIB cervical cancer in
      Japanese women.
AB  - Chemoradiotherapy is currently the main treatment for locally advanced cervical
      cancer, but neoadjuvant intraarterial chemotherapy (IA-NAC) has been reported to
      achieve favorable results. This study investigated the efficacy of several
      different IA-NAC regimens. The subjects were 55 patients with stage IIB-IIIB
      cervical cancer who received IA-NAC between January 1991 and April 2006. IA-NAC
      was administered for a total of 1-3 courses at 3-week intervals, with three
      different regimens being employed in chronological order. The response rate
      achieved with IA-NAC was 90.2% for squamous cell carcinoma, 60% for adenosquamous
      carcinoma and 42.9% for adenocarcinoma. Surgery was performed after IA-NAC in 36
      patients, and radiotherapy alone was performed in 19 patients. The 5-year
      survival rate was 72.9% for patients with squamous cell carcinoma and 50% for
      those with adenocarcinoma or adenosquamous carcinoma. PAMF therapy (cisplatin,
      epirubicin, mitomycin-C and 5-fluorouracil) achieved a response rate of >=90% for
      squamous cell carcinoma, as did CDDP + THP therapy (cisplatin plus pirarubicin),
      while PACF therapy (cisplatin, epirubicin, cyclophosphamide and 5-flurouracil)
      achieved a better response rate for adenosquamous carcinoma and adenocarcinoma.
      Grade 3 or 4 hematological toxicity was significantly more common with PAMF
      therapy. In conclusion, IA-NAC improved the survival of patients with squamous
      cell carcinoma. CDDP + THP therapy achieved a high response rate with little
      hematologic toxicity. PACF therapy achieved a significantly higher response rate
      in patients with adenosquamous carcinoma or adenocarcinoma. Therefore, IA-NAC may
      be a therapeutic option for locally advanced cervical cancer, particularly using
      the above-mentioned regimens.

PMID- 22993590
TI  - Sensitive quantitative assay for point mutations in the rat H-ras gene based on
      single nucleotide primer extension.
AB  - Point mutations in oncogenes and tumor suppressor genes occur at early stages in
      the carcinogenic process. Point mutations in ras family oncogenes are the most
      common mutational events in several types of human cancer, and are available as
      molecular markers for the detection of cancer cells in carcinogenicity bioassay
      systems as well as in clinical samples. Although several techniques are utilized
      to detect point mutations in carcinogenicity bioassay systems, the sensitivity is
      too low to determine a small number of mutations. In order to overcome the
      disadvantage and to sensitively determine gene mutation rates for in vivo
      carcinogenicity bioassays of presumptive carcinogens, we established a
      Thermosequenase Cycle End Labeling (TCEL) method, a sensitive approach based on
      single nucleotide primer extension. One of the characteristics of the method is a
      high sensitivity of 1:100,000, ten times the sensitivity of the mutant allele
      specific amplification now commonly employed. Using TCEL, we here quantified H
      ras mutations in the livers of rats treated with a genotoxic carcinogen, 2-amino
      3,8-dimethylimidazo[4,5-f]quinoxaline. Our findings suggest that this method may
      be applied for many genetic targets as a component in vivo.

PMID- 22993591
TI  - Effects of irbesartan on 24-h blood pressure changes and urinary albumin levels
      in Japanese outpatients.
AB  - In Japan, ambulatory blood pressure monitoring (ABPM) became covered by health
      insurance in April 2008. In The Japanese Society of Hypertension Guidelines for
      the Management of Hypertension (JSH2009), the importance of 24-h blood pressure
      monitoring was also described in an additional section. Therefore, ABPM may be
      increasingly applied in hypertension treatment. However, in Japan, few studies
      have presented data on the effects of various anti-hypertensive agents on 24-h
      blood pressure changes. Irbesartan became commercially available in July 2008 as
      the sixth angiotensin II type 1 receptor blocker in Japan. In the present study,
      24-h blood pressure control was examined using ABPM in Japanese patients with
      essential hypertension who were treated with irbesartan, and its efficacy was
      evaluated. This study was completed in 30 of the 32 subjects. This agent
      decreased both the nocturnal and daytime blood pressures and reduced the rate of
      change in the systolic blood pressure early in the morning, resulting in
      favorable blood pressure control. It also significantly decreased the urinary
      albumin level, suggesting that it exhibits renoprotective effects at doses
      approved in Japan.

PMID- 22993592
TI  - Association between polymorphisms of the DBH and DAT1 genes and attention deficit
      hyperactivity disorder in children from Jordan.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common
      neuropsychiatric disorders in children. In this study, the association between 10
      repeats in the DAT1 gene and the (GT)n repeat in the DBH gene and ADHD was
      examined in children from Jordan. In addition, the levels of dopamine-beta
      hydroxylase enzyme activity in the plasma of ADHD children were evaluated. Fifty
      children with ADHD and 50 age- and gender-matched control subjects were
      recruited. The results showed significant differences between the ADHD group and
      controls with respect to the plasma levels of dopamine-beta-hydroxylase enzyme
      activity (25.4+/-2.3 vs. 84.7+/-5.0 MUmol/min; p<0.01). Moreover, the 10-repeat
      DAT1 gene and (GT)n DBH gene polymorphisms were significantly associated with
      ADHD development (p<0.05). In conclusion, the DBH and DAT1 genes appear to play a
      role in the development of ADHD in the Jordanian population.

PMID- 22993593
TI  - Insulin resistance derived from zinc deficiency in non-diabetic patients with
      chronic hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection frequently evokes metabolic
      abnormalities including insulin resistance. A decrease in serum zinc (Zn) levels
      is often observed in association with hepatic fibrosis. Zn also plays important
      roles in insulin secretion. However, little is known about the relationship
      between Zn deficiency and insulin resistance in patients with HCV-related chronic
      liver disease. The main purpose of this study was to examine the contribution of
      Zn deficiency to insulin resistance in patients with chronic hepatitis C (CH-C).
      Forty-eight non-diabetic patients with CH-C were enrolled. Serum alanine
      aminotransferase (ALT), ferritin and Zn levels were examined in the enrolled
      patients with CH-C. Insulin resistance was determined by the Homeostasis model
      for assessment of insulin resistance (HOMA-IR). Zn deficiency was defined as
      serum Zn levels <65 MUg/dl. Seven out of the 48 (15%) patients with CH-C
      fulfilled the criteria for Zn deficiency. Serum Zn levels were inversely
      correlated with serum ferritin levels (r=-0.364, p=0.0140). The values of HOMA-IR
      were positively linked to serum ferritin levels (r=0.299, p=0.0484). The mean
      value of HOMA-IR in the Zn deficiency group was significantly higher than that in
      the normal-range Zn group (3.76+/-0.66 vs. 2.08+/-1.35, p=0.0019). Serum ALT
      levels were also closely associated with serum ferritin levels (r=0.727,
      p<0.001). These findings were independent of HCV genotypes or loads of HCV-RNA.
      Our data suggest that iron overload in patients with CH-C derives from Zn
      deficiency and thereby causes insulin resistance.

PMID- 22993594
TI  - Comparative photodynamic therapy study using two phthalocyanine derivatives.
AB  - In the present study, a comparative photodynamic therapy (PDT) study was
      performed using the phthalocyanine derivatives, ZnPc(OCH(3))(4) and
      ZnPc(CF(3))(4), in a mouse tumor model, under identical experimental procedures.
      We studied the ablation of tumors induced by PDT. The end-point was to compare
      the photodynamic efficacy of ZnPc(OCH(3))(4) and ZnPc(CF(3))(4). ZnPc(OCH(3))(4)
      and ZnPc(CF(3))(4) were administered intraperitoneally at a dose of 0.2 mg/kg
      body weight. The injections of drugs were carried out in Balb/c mice bearing
      subcutaneously inoculated LM2 mouse mammary adenocarcinoma. Histological
      examination and serum biochemical parameters were used to evaluate hepatic and
      renal toxicity and function. Phototherapeutic studies were achieved employing a
      light intensity of 210 J/cm(2). After PDT, tumoral regression analyses were
      carried out, and the degree of tumor cell death was measured utilizing the vital
      stain Evan's blue. In this pilot study, we revealed that the cytotoxic effect of
      ZnPc(OCH(3))(4) after PDT led to a higher success rate compared to ZnPc(CF(3))(4)
      PDT when both were intraperitoneally injectioned. Both phthalocynanine
      derivatives were able to induce ablation in the tumors. In summary, these results
      demonstrate the feasibility of ZnPc(OCH(3))(4)- or ZnPc(CF(3))(4)-PDT and its
      potential as a treatment for small tumors.

PMID- 22993595
TI  - Association of endothelial nitric oxide synthase polymorphisms with coronary
      artery disease in Korean individuals with or without diabetes mellitus.
AB  - Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been
      implicated in various diseases, but their roles as risk factors in type 2
      diabetes mellitus (T2DM) with regard to coronary artery disease (CAD) are largely
      unknown. Therefore, we investigated the association of the genotypes and
      haplotypes of eNOS polymorphisms in CAD with T2DM. A case-control study was
      performed to evaluate the genotypes and haplotypes of the eNOS polymorphisms (
      786T>C, 4a4b and 894G>T) in 192 CAD patients and 196 controls. The same
      population was also re-organized upon the status of T2DM. The genotypes of eNOS 
      786T>C, 4a4b and 894G>T polymorphisms were determined by polymerase chain
      reaction-restriction fragment length polymorphism. We found that eNOS -786TC+CC
      and 4a4b+4a4a genotypes were significantly prevalent in the diabetic controls and
      the diabetic CAD patients compared to the non-diabetic controls or non-diabetic
      CAD patients, respectively. The frequency of the -786C-4a-894G haplotype was
      significantly greater in the diabetic CAD patients (p=0.001) and diabetic
      controls (p=0.023) compared to the non-diabetic controls, whereas the haplotype
      of -786T-4b-894G was less prevalent in the diabetic CAD patients compared to the
      non-diabetic controls (p=0.018). Significant associations of the genotypes and
      the haplotypes were consistently observed in the T2DM group compared to non-DM
      group, regardless of CAD status. Our finding suggests that the eNOS -786T>C and
      4a4b polymorphisms and the -786C-4a-894G haplotype are risk factors for T2DM,
      whereas the haplotype of -786T-4b-894G has a protective effect against the
      development of T2DM.

PMID- 22993596
TI  - Gas plasma sterilization of microorganisms and mechanisms of action.
AB  - The use of true gas plasmas for the inactivation of microorganisms is an area of
      dynamic research. Many types of gases are used as a source of plasma, and
      different plasma production methods have been applied. The antimicrobial
      mechanisms of oxygen-based gas plasmas may be due to an etching effect on
      microbial structures, particularly bacterial endospores resulting in shrinkage.
      By contrast, the definite mechanisms of actions of other gas plasma sources, such
      as N(2), He, Ne, Ar and Xe gases, have not been clearly defined and indeed may be
      distinct. The speculated mechanisms of these gas plasmas involve the direct
      attack of metastable (excited molecular), UV and/or VUV to microbial structures,
      specifically the inner membrane and DNA in the core of bacterial endospores.
      According to this speculation, sterilized spore figures would remain unchanged.
      However, these mechanisms remain to be clarified. Future perspectives on the use
      of gas plasma for sterilization are of interest, as it is possible that
      appropriate sterility assurance levels can be obtained in parallel with material
      and functional compatibility. Traditional sterilization methods are often limited
      in these requirements. Therefore, gas plasma sterilization may prove to be an
      appropriate alternative sterilization procedure.

PMID- 22993597
TI  - Inhibition of tumor angiogenesis by oral etoposide.
AB  - The chemotherapeutic agent etoposide is a topoisomerase II inhibitor widely used
      for cancer therapy. Low-dose oral etoposide, administered at close regular
      intervals, has potent anti-tumor activity in patients who are refractory to
      intravenous etoposide; however, the mechanism remains unclear. Since endothelial
      cells may be more sensitive than tumor cells to chemotherapy agents, we
      determined the effects of etoposide alone and in combination with oral
      cyclooxygenase-2 inhibitors and peroxisome-proliferator activated receptor gamma
      ligands on angiogenesis and tumor growth in xenograft tumor models. Optimal anti
      angiogenic (metronomic) and anti-tumor doses of etoposide on angiogenesis,
      primary tumor growth and metastasis were established alone and in combination
      therapy. Etoposide inhibited endothelial and tumor cell proliferation, decreased
      vascular endothelial growth factor (VEGF) production by tumor cells and
      suppressed endothelial tube formation at non-cytotoxic concentrations. In our in
      vivo studies, oral etoposide inhibited fibroblast growth factor 2 and VEGF
      induced corneal neovascularization, VEGF-induced vascular permeability and
      increased levels of the endogenous angiogenesis inhibitor endostatin in mice. In
      addition, etoposide inhibited Lewis lung carcinoma (LLC) and human glioblastoma
      (U87) primary tumor growth as well as spontaneous lung metastasis in a LLC
      resection model. Furthermore, etoposide had synergistic anti-tumor activity in
      combination with celecoxib and rosiglitazone, which are also oral anti-angiogenic
      and anti-tumor agents. Etoposide inhibits angiogenesis in vitro and in vivo by
      indirect and direct mechanisms of action. Combining etoposide with celecoxib and
      rosiglitazone increases its efficacy and merits further investigation in future
      clinical trials to determine the potential usefulness of etoposide in combinatory
      anti-angiogenic chemotherapy.

PMID- 22993598
TI  - Ki-67 as a prognostic marker according to breast cancer subtype and a predictor
      of recurrence time in primary breast cancer.
AB  - The choice of adjuvant systemic therapy is based on targeted therapy in line with
      the St. Gallen Consensus meeting. In addition to the traditional parameters, the
      panel recommended the use of proliferation markers and multigene assays. The
      purpose of the present study was to evaluate the clinical significance of
      proliferative activity using the Ki-67 index as a prognostic marker and as a
      predictor of recurrence time in breast cancer patients. The Ki-67 index was
      measured in 3,652 cases with primary breast cancer from 1987 to 2009. Out of
      these patients, 2,638 cases were evaluated simultaneously for estrogen receptor,
      progesterone receptor and HER2 from 1997, and these were analyzed as a prognostic
      factor according to their subtypes. The Ki-67 index exhibited a wide range of 1
      99%, with a median of 20%, and cases were divided into 2 or 3 index groups; <20%
      and >=20% (and >=50%). The median Ki-67 index of tumors with luminal A was 17%,
      and that of luminal B type tumors was 29%. The Ki-67 index of HER2 tumors was 40%
      and that of triple negative tumors was 50%. A higher Ki-67 index significantly
      correlated with a higher grade of malignancy. Patients with a higher Ki-67 index
      had significantly lower disease-free survival (DFS) and overall survival rates.
      Moreover, there was a significant difference in the recurrence time. Multivariate
      analysis revealed that the Ki-67 index was a significant factor for DFS,
      irrespective of nodal status, and that Ki-67 was a significant marker only in
      luminal A type tumors. Furthermore, luminal A type cases with high Ki-67 had a
      similar DFS as the luminal B type cases. A higher Ki-67 index (>=20%)
      significantly correlated with other biological markers, poorer prognosis and
      early recurrence, particularly in luminal A type tumors. It is important to take
      the Ki-67 index into consideration in the treatment and follow-up of breast
      cancer patients.

PMID- 22993599
TI  - Osteoclast-related cytokines from biopsy specimens predict mandibular invasion by
      oral squamous cell carcinoma.
AB  - The aim of this study was to examine the value of osteoclast-related cytokines in
      biopsy specimens for predicting mandibular invasion by oral squamous cell
      carcinoma (OSCC). In this retrospective study, biopsy specimens were obtained
      from 30 patients with OSCC. We observed the expression of seven osteoclast
      related cytokines (IL-1alpha, RANKL, PTHrP, OPG, IL-6, RANK and TNF-alpha) using
      immunohistochemical (IHC) staining and of an osteoclast using tartrate-resistant
      acid phosphatase (TRAP) staining. The results were as follows: i) double-staining
      and IHC staining for RANKL, PTHrP and IL-1alpha in biopsy samples had diagnostic
      potential for predicting mandibular invasion; ii) TRAP-positive monoor
      multinuclear cells were noted in the biopsy samples; iii) double-positive or 
      negative findings appeared to reliable indicate whether samples were invasion
      positive or invasion-negative. Positive IHC staining for PTHrP, IL-1alpha or
      RANKL appeared to typically indicate an invasion-positive lesion. We suggest that
      the expression of both osteoclasts and osteoclast-related cytokines can be used
      to predict mandibular invasion.

PMID- 22993601
TI  - Effectiveness of oral iron to manage anemia in long-term hemodialysis patients
      with the use of ultrapure dialysate.
AB  - The aim of this study was to evaluate the effectiveness of oral iron to manage
      anemia in long-term hemodialysis (HD) patients using ultrapure dialysate. This
      study was prospectively conducted on 23 patients (11 males and 12 females; median
      age 60 years, range 35-81) who underwent HD in our hospital from March to
      September 2007. The patients were randomly assigned to two treatment groups. The
      first group of 11 patients received ferrous fumarate 305 mg per oral tablet once
      a day, while the second group of 12 patients received infusions of 50 mg iron in
      a 0.9% sodium chloride solution. At the end of the 6-month treatment, patients
      receiving oral iron and intravenous iron had a significant increase in
      transferrin saturation from baseline (20.1+/-8.9 to 29.7+/-7.2; p=0.011 and
      17.4+/-6.1 to 33.7+/-8.6; p=0.0001, respectively) and ferritin (32.6+/-15.4 to
      115.4+/-28.2; p=0.0001 and 57.8+/-26.7 to 183.5+/-47.5; p=0.0002, respectively).
      In both groups, hemoglobin, hematocrit and dry weight were increased, but did not
      reach statistical significance. Moreover, both groups showed a significant
      reduction in the mean weekly erythropoietin dose from baseline (5,590.9+/-1,513.6
      to 3,727.3+/-1,618.1; p=0.011 and 6,775.8+/-2,292.2 to 4,375.0+/-2,473.7;
      p=0.027, respectively). Oral iron is indeed as effective as intravenous iron in
      managing anemia in HD patients using ultrapure dialysate.

PMID- 22993600
TI  - Non-surgical therapy and radiologic assessment of stage I breast cancer treatment
      with novel enzyme-targeting radiosensitization: Kochi Oxydol-Radiation Therapy
      for Unresectable Carcinomas, type II (KORTUC II).
AB  - The new enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation
      Therapy for Unresectable Carcinomas, type II (KORTUC II), markedly enhances the
      radiotherapeutic effect of treatment for various types of locally advanced
      malignant neoplasms. Patients who had declined surgical treatment and systemic
      chemotherapy, as well as a total of 14 stage I breast cancer patients, were
      enrolled. A maximum of 6 ml of KORTUC II was injected into tumor tissue twice a
      week under ultrasonographic guidance, immediately prior to each administration of
      radiation therapy. The median observation period was 21.6 months with a range of
      4-48 months, and the therapy was well tolerated. Contrast-enhanced magnetic
      resonance imaging and [(18)F]-fluorodeoxyglucose positron emission computed
      tomography revealed that all primary breast tumors completely responded, and none
      of the subjects experienced local recurrence during the observation period.
      Ultrasonography depicted tumor-like findings in 2/14 cases after therapy. The
      intratumoral flow signal on color-Doppler sonography was positive in 4/14 cases
      before therapy, and the signal disappeared from all cases after therapy. The
      absence of a flow signal after therapy suggested that the tumor-like findings on
      ultrasonography were from scar tissue. Excellent local control based on accurate
      radiological evaluation implies that KORTUC II has the potential to replace
      surgery as a therapeutic option for stage I breast cancer. Precise evaluation by
      various radiological modalities helped to gage the success of this therapy.

PMID- 22993602
TI  - Prognostic significance of the mitochondrial scoring system in ovarian cancer.
AB  - We report a mitochondrial (MT) scoring system related to response to platinum
      treatment in ovarian cancer (OC). Ultra-thin sections of surgical specimens of
      primary tumors prepared from 41 OC patients were examined by electron microscopy.
      The ovarian carcinoma cell line 2008 and its platinum-resistant variant C13 were
      used as controls. Seven independent MT features, including MT diameter, pattern
      of cresta structure, electron density, MT distribution, pattern of distribution,
      ovoid ratio and MT architecture, were examined. Each of the seven parameters was
      assigned a point score of 0-2 and was summed up with a total score of 14.
      Clinical response and in vitro sensitivity to platinum, taxane, irinotecan and
      doxorubicin were evaluated. Clinical information was available for 37 of the 41
      cases. Twenty-four cases were stage III and, histologically, 16 serous, 6
      endometrioid and 6 clear cell carcinoma were included. All of the patients
      underwent surgery followed by 6 cycles of taxane and platinum chemotherapy.
      Fifteen patients exhibited a response, while 22 were resistant to treatment. The
      total MT score was 5.13+/-1.13 (mean +/- SE) in the 15 responsive cases and
      11.41+/-0.43 in the 22 resistant cases (P<0.001). Receptor operative
      characteristic (ROC) analysis revealed that the resistant total 'cut-off' score
      was >=10 points (P<0.05; AUC=0.86) with 95.5% sensitivity and 80.0% specificity.
      The MT scoring system correlated well with response to drugs, with the exception
      of doxorubicin. The progression-free survival (PFS) curves showed an absolute
      difference in the 6-month PFS of 10% (83 vs. 73%) and in the 12-month PFS of 21%
      (80 vs. 59%), in favor of patients with low MT scores. This MT scoring system
      correlates very closely with clinical response as well as cellular sensitivity to
      chemotherapy, resulting in an association with PFS.

PMID- 22993603
TI  - Claudin-4 expression is associated with tumor invasion, MMP-2 and MMP-9
      expression in gastric cancer.
AB  - Claudin-4 is a member of the claudin family, a large family of transmembrane
      proteins that are essential in the formation and maintenance of tight junctions.
      Matrix metal-loproteinase (MMP)-2 and -9 degrade type IV collagen of the
      extracellular matrix and basal membranes. Claudin-4 activates MMP-2, indicating
      that claudin-mediated increased cancer cell invasion may result from the
      activation of MMP proteins. In the present study, we used immunohistochemistry to
      examine the expression levels of claudin-4, MMP-2 and MMP-9 in 189 gastric cancer
      samples, and analyzed their correlation with tumor invasion, clinicopathologic
      parameters and clinical outcome. The relationship between claudin-4 expression
      and MMP-2 and -9 expression was also investigated. The expression of claudin-4
      was found to be significantly higher in gastric cancer cases with advanced depth
      of wall invasion, lymph node metastasis, lymphatic invasion and higher TNM stage.
      Further analysis revealed claudin-4 expression to be significantly correlated
      with the expression of MMP-2 and -9. Kaplan-Meier survival analysis indicated
      that MMP-9 expression was correlated with poor prognosis. These results suggest
      that claudin-4 expression is associated with tumor invasion and with MMP-2 and -9
      expression in gastric cancer. Additionally, MMP-9 expression was demonstrated to
      serve as a prognostic factor in patients with gastric cancer.

PMID- 22993604
TI  - Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy
      chain (CD98) expression in surgically resectable stage III non-small cell lung
      cancer.
AB  - The purpose of this study was to evaluate the prognostic value of L-type amino
      acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in patients with
      stage III non-small cell lung cancer (NSCLC). A total of 188 consecutive patients
      with pathologic stage III NSCLC were retrospectively reviewed. The expression of
      LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF) as
      well as microvessel density (MVD) were evaluated immunohistochemically and
      correlated with the prognosis of patients after complete resection of the tumor.
      Positive expression of LAT1 and CD98 was noted in 58% (109/188) and 50% (94/188)
      of the cases, respectively (p=0.1473). A positive rate of LAT1 expression was
      significantly higher in squamous cell carcinoma (SQC) (90%, 48/53) and large-cell
      carcinoma (LCC) (100%, 12/12) than in adenocarcinoma (AC) (40%, 49/123).
      Moreover, a positive rate of LAT1 with CD98 expression was also significantly
      higher in SQC (74%, 39/53) and LCC (75%, 9/12) than AC (34%, 42/123). LAT1
      expression was significantly higher in patients with mediastinal lymph node
      metastases than in patients without, and was significantly correlated with CD98,
      Ki-67 labeling index, VEGF and MVD. The 5-year survival rates of LAT1-positive
      and -negative patients and CD98-positive and -negative patients were 27.9 and
      40.6% (p=0.0033), respectively, and 24.1 and 43.6% (p=0.0004), respectively.
      Multivariate analysis confirmed that positive expression of LAT1 and CD98 was an
      independent factor predicting a poor prognosis. In conclusion, the overexpression
      of LAT1 and CD98 is a pathological factor for predicting the prognosis of
      patients with surgically resectable stage III NSCLC.

PMID- 22993605
TI  - Characteristic expression pattern of oxidative stress in livers with cryptogenic
      hepatocellular carcinoma.
AB  - The mechanism responsible for the development of hepatocellular carcinoma (HCC)
      in the setting of oxidative stress has yet to be clearly defined. We studied the
      role of oxidative stress in hepatocarcinogenesis in subjects without underlying
      chronic viral hepatitis. The subjects were 24 patients negative for serum
      hepatitis B surface antigen and hepatitis C antibody tests, who underwent hepatic
      resection for HCC (Group N). Subjects were excluded if diagnosed with liver
      disease predisposing to HCC. Immunohistochemical staining for oxidative stress
      related markers was performed on non-cancerous liver regions. Resected liver
      tissues adjacent to HCC from 24 patients with chronic hepatitis B (Group B) and
      21 patients with chronic hepatitis C (Group C) were also examined. The percentage
      of 8-hydroxydeoxyguanosine-positive hepatocytes in Group N was significantly
      lower than that in Group B and that in the combined population of Groups B and C.
      The percentage of the area positive for 4-hydroxynonenal in Group N was
      significantly higher than that in Groups B or C. Meanwhile, the percentage of the
      area positive for manganese superoxide dismutase in Group N was not different
      from that in Groups B and C. In conclusion, the mechanism of hepatocarcinogenesis
      through oxidative stress for patients without known liver disease predisposing to
      HCC may differ from that for patients with chronic viral hepatitis.

PMID- 22993606
TI  - Evaluation of the effects of a supplementary diet containing chicken comb extract
      on symptoms and cartilage metabolism in patients with knee osteoarthritis.
AB  - We aimed to investigate whether a supplementary diet containing chicken comb
      extract (CCE) rich in hyaluronic acid (HA) has an effect on pain and other
      symptoms, as well as cartilage type II collagen (CII) metabolism in patients with
      knee osteoarthritis (OA). A randomized double-blind placebo-controlled study was
      conducted in 43 subjects with knee OA (Kellgren/Lawrence grade, mainly 1-2)
      comprising 22 patients receiving concurrent exercise therapy (ET) and 21 without
      ET (referred as ET-receivers and ET-unreceivers, respectively). Subjects were
      randomized to a CCE-containing diet (active diet) group administered a dose of
      1,800 mg/day (containing 630 mg of CCE and approximately 60 mg of HA) and a
      placebo group, and the intervention was continued for 16 weeks. Symptomatic
      efficacy was evaluated based on the Japanese Orthopaedic Association clinical
      trials response criteria (JOA response criteria) and Visual analog scales (VAS)
      before (baseline) and during the intervention. To further examine its effect on
      CII metabolism, the levels of two degradation biomarkers (CTX-II and C2C) and one
      synthesis biomarker (CPII) were measured using urine or serum samples. Nineteen
      subjects (10 ET-receivers and 9 ET-unreceivers) in the active diet group and 21
      subjects (10 ET-receivers and 11 ET-unreceivers) in the placebo group were
      finally included in the study. Compared to the baseline, subscale scores of the
      JOA response criteria, i.e., 'pain/walking function', 'pain/step-up and -down
      function' and 'aggregate total symptoms' were more intensely improved in the
      active diet group than in the placebo group. Moreover, subgroup analyses of ET
      receivers and ET-unreceivers indicated that significant improvements were
      restricted to ET-receivers of the active diet group. Furthermore, VAS assessment
      indicated that the 'pain on pressing' subscale was significantly improved in ET
      receivers of the active diet group. In addition, analysis of CII biomarkers
      revealed that serum C2C and CPII levels, but not the urinary CTX-II level, were
      increased in the active diet group. Notably, both urinary CTX-II/serum CPII and
      serum C2C/serum CPII ratios were reduced in the active diet group (particularly
      ET-unreceivers), suggesting that CII synthesis was relatively increased compared
      to CII degradation in the active diet group. Finally, no diet-related side
      effects were observed. The CCE-containing diet is likely to be effective in
      relieving symptoms in patients with knee OA. In addition, it has the potential to
      improve the balance of CII degradation/synthesis in knee OA.

PMID- 22993607
TI  - A beta-tubulin 5-derived peptide induces cytotoxic T lymphocytes restricted to
      the HLA-A24 allele in prostate cancer patients.
AB  - To facilitate the development of a peptide-based cancer vaccine for prostate
      cancer patients, we examined whether any of the 13 peptides previously reported
      to induce HLA-class I-restricted cytotoxic T lymphocyte (CTL) activity in HLA-A3
      supertype (-A3, -A11, -A31 and -A33)-positive prostate cancer patients are also
      capable of inducing CTLs restricted to HLA-A2, HLA-A24 or HLA-A26 alleles. Among
      the 13 peptides tested, a peptide at positions 309 to 318 of beta-tubulin 5
      exhibited binding activity to the HLA-A(*)2402 molecule and induced HLA-A24
      restricted CTL activity against prostate cancer cells derived from peripheral
      blood mononuclear cells of prostate cancer patients. The CTL activity was
      determined to be specific to this peptide and was mediated by CD8(+) T cells in
      an HLA-class I-restricted manner. These results suggest that this peptide could
      be applicable as a peptide vaccine, not only for HLA-A3 supertype-positive, but
      also for HLA-A24-positive prostate cancer patients.

PMID- 22993608
TI  - Decreased expression of FBXW7 is correlated with poor prognosis in patients with
      esophageal squamous cell carcinoma.
AB  - FBXW7 is a tumor suppressor gene that induces the degradation of positive cell
      cycle regulators such as c-Myc, cyclin E, c-Jun and Notch. The loss of FBXW7
      promotes cell-cycle progression and cell proliferation. In the present study, we
      investigated the relationship between FBXW7 expression and the
      clinicopathological characteristics of patients with esophageal squamous cell
      carcinoma (ESCC). The expression of FBXW7 was quantified by real-time reverse
      transcription polymerase chain reaction in 43 primary ESCCs and their paired
      normal esophageal mucosa in patients who had not received preoperative therapy.
      FBXW7 expression levels were significantly correlated with the progression of the
      cancer and with local invasiveness. In muscle-invasive tumor cases (T2-4),
      lymphatic invasive tumor cases and stage II-IV cases, FBXW7 expression levels
      were significantly decreased (P=0.0315, P=0.0336 and P=0.0289, respectively).
      Decreased expression of FBXW7 was correlated with poor prognosis (P=0.0255). In
      conclusion, this study examined the relationship between FBXW7 expression and
      tumor progression in ESCC. We suggest that FBXW7 is a molecular prognostic marker
      and can be used to elucidate the mechanism of carcinogenesis.

PMID- 22993609
TI  - Gemcitabine and paclitaxel suppress the production of vascular endothelial growth
      factor induced by deferoxamine in human non-small cell lung cancer A549 cells.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in the process
      of angiogenesis in many types of cancer, including non-small cell lung cancer
      (NSCLC), and angiogenesis inhibitors and standard chemotherapy exhibit synergy
      though an unknown mechanism. We therefore hypothesized that cytotoxic
      chemotherapy influences VEGF production and analyzed VEGF production in an NSCLC
      A549 cell line after treatment with standard chemotherapy. Paclitaxel inhibited
      the production of VEGF in A549 cells, while cisplatin and erlotinib did not.
      Paclitaxel and gemcitabine inhibited deferoxamine (DFX) (known to mimic hypoxia)
      induced VEGF production in A549 cells. Erlotinib also inhibited DFX-induced VEGF
      production in A549 cells slightly, while cisplatin did not. We subsequently
      examined the effect of the interaction between paclitaxel or gemcitabine and VEGF
      protein. Paclitaxel and gemcitabine did not directly affect the binding of VEGF.
      Since VEGF is known as one of the HIF-1 target genes, we examined the effect of
      paclitaxel and gemcitabine on HIF-1alpha levels induced by DFX in A549 cells.
      Paclitaxel and gemcitabine inhibited DFX-induced HIF-1alpha in A549 cells. These
      findings may be useful for future treatment schedules, including anti-cancer
      agents in NSCLC.

PMID- 22993610
TI  - Sorafenib suppresses the cell cycle and induces the apoptosis of hepatocellular
      carcinoma cell lines in serum-free media.
AB  - To suppress the invasion of hepatocellular carcinoma (HCC) cells into surrounding
      connective tissues during metastasis, we investigated the usefulness of
      sorafenib. In order to search for model cell lines, cell numbers were counted to
      reveal cell lines with the potential to proliferate in serum-free media. Cell
      proliferation and cell motility were analyzed with the MTS and wound assay,
      respectively. 5-Bromo-2'-deoxyuridine (BrdU) labeling and mitotic and apoptotic
      indices were analyzed to assess the cell cycle and apoptosis. The expression
      levels of cyclin D1 and the cleavage of caspase-3 were analyzed by Western
      blotting. HLF cells exhibited growth in the serum-free medium, while the other
      cell lines examined did not. Sorafenib suppressed the cell proliferation and
      motility of the HLF cells in the serum-free media. Both indices of BrdU and
      mitotic potential decreased and the apoptotic index was increased in the serum
      free media with sorafenib, suggesting that the cell cycle was suppressed and
      apoptosis was induced. The expression levels of cyclin D1 decreased and the
      cleavage of caspase-3 was noted in the serum-free media with sorafenib. Sorafenib
      may be suitable for molecular therapy to suppress the metastasis of HCC.

PMID- 22993611
TI  - High-risk early breast cancer in patients under 40 years of age: Improved
      clinical outcome with total estrogen blockade and tailored chemotherapy.
AB  - This multicenter prospective trial assessed the outcome in 63 patients, 40 years
      of age or younger, with high-risk early breast cancer (HREBC), included in an
      ovarian protection study. The patients were treated with a luteinizing hormone
      releasing hormone (LH-RH) analogue administered for 5 years, tailored
      chemotherapy and an aromatase inhibitor, in estrogen receptor-positive (ER(+))
      patients. T-regulatory cells (T-regs) and vascular endothelial growth factor
      (VEGF) were measured at baseline and yearly. The mean age of the patients was 36
      years (range 26-40). Sixty-five percent had ER(+) tumors, 24% had negative
      axillary nodes with tumors >1 cm and high histological grade with lymphovascular
      invasion, while 76% had a mean of 3.6 positive axillary nodes (range 1-21). Serum
      estradiol was maintained at values <40 pg/ml in all of the patients. A
      statistically significant decrease in VEGF (P<0.0001) and T-regs (P<0.0001), with
      respect to baseline values, was observed after LH-RH administration. After a
      median follow-up of 110 months, the 10-year progression-free and overall survival
      rates were 86.1 and 89.7%, respectively. These data revealed that the
      administration of an LH-RH analogue to HREBC patients, followed by chemotherapy
      and hormonal therapy, decreased VEGF and T-regs and improved the expected
      clinical outcome.

PMID- 22993612
TI  - Concentrations of IL-15, IL-18, IFN-gamma and activity of CD4+, CD8+ and NK cells
      at admission in children with viral bronchiolitis.
AB  - The pathogenesis of viral bronchiolitis is poorly understood. The aim of this
      study was to analyze interleukin (IL)-15, IL-18 and interferon (IFN)-gamma
      concentrations and the activity of NK cells and CD4+ and CD8+ lymphocytes in 23
      children not older than 30 months of age with acute viral bronchiolitis using
      blood samples drawn within the first 24 h of their hospital admission, in
      comparison to a healthy group. In children with bronchiolitis, the mean
      concentrations of IL-15, IL-18 and IFN-gamma were 9.39+/-11.55, 884.03+/-645.44
      and 17.92+/-27.14 pg/ml, respectively, and were significantly higher than those
      in the control group [2.34+/-0.61 pg/ml (p<0.05), 248.69+/-98.73 pg/ml (p<0.001)
      and 2.75+/-1.72 pg/ml (p<0.005), respectively]. In the bronchiolitis group, mean
      z-scores were -1.15+/-1.9 for CD4+ cells and -0.9+/-1.23 for CD8+ cells; these
      scores were significantly lower than those of the general Polish population
      (p<0.001 and <0.01, respectively). However, the mean z-score of the ratio of
      CD4+/CD8+ and the NK cell count in children with bronchiolitis did not differ
      significantly from those of the controls. In conclusion, cytokines such as IL-15,
      IL-18 and IFN-gamma play a role in the pathogenesis of bronchiolitis in children.

PMID- 22993613
TI  - APC Yin-Yang haplotype associated with colorectal cancer risk.
AB  - The Yin-Yang haplotype is defined as two mismatched haplotypes (Yin and Yang)
      representing the majority of the existing haplotypes in a particular genomic
      region. The human adenomatous polyposis coli (APC) gene shows a Yin-Yang
      haplotype pattern accounting for 84% of all of the haplotypes existing in the
      Spanish population. Several association studies have been published regarding APC
      gene variants (SNPs and haplotypes) and colorectal cancer (CRC) risk. However, no
      studies concerning diplotype structure and CRC risk have been conducted. The aim
      of the present study was to investigate whether the APC Yin-Yang homozygote
      diplotype is over-represented in patients with sporadic CRC when compared to its
      distribution in controls, and its association with CRC risk. TaqMan((r)) assays
      were used to genotype three tagSNPs selected across the APC Yin-Yang region.
      Frequencies of the APC Yin-Yang tagSNP alleles, haplotype and diplotype of 378
      CRC cases and 642 controls were compared. Two Spanish CRC group samples were
      included [Hospital Clinico San Carlos in Madrid (HCSC) and Instituto Catalan de
      Oncologia in Barcelona (ICO)]. Analysis of 157 consecutive CRC patients and 405
      control subjects from HCSC showed a significative effect for the risk of CRC
      (OR=1.93; 95% CI 1.32-2.81; P=0.001). However, this effect was not confirmed in
      221 CRC patients and 237 control subjects from ICO (OR=0.89; 95% CI 0.61-1.28;
      P=0.521). We found a significant association between the APC homozygote Yin-Yang
      diplotype and the risk of colorectal cancer in the HCSC samples. However, we did
      not observe this association in the ICO samples. These observations suggest that
      a study with a larger Spanish cohort is necessary to confirm the effects of the
      APC Yin-Yang diplotype on the risk of CRC.

PMID- 22993614
TI  - Relation between proinflammatory mediators and epithelial-mesenchymal transition
      in head and neck squamous cell carcinoma.
AB  - Increasing evidence suggests that the tumor microenvironment plays an important
      role in tumor progression and oncogenesis. Various proinflammatory mediators
      contribute to tumor proliferation, neoangiogenesis, invasion, metastasis, and
      resistance to cancer therapy such as hormonal therapy and chemotherapy. The major
      causes of death related to head and neck squamous cell carcinoma (HNSCC) include
      cervical node and distant metastases. Epithelial-mesenchymal transition (EMT) has
      been identified to play a key role in mediating the tumor invasion and metastasis
      of carcinomas. Herein, the relationship between proinflammatory mediators and EMT
      in HNSCC was investigated. Immunohistochemical expression of interleukin-1 beta
      (IL-1beta), cyclooxygenase-2 (COX-2), Slug and E-cadherin in relationship to
      histologic differentiation, clinical stage and nodal status was evaluated in 146
      surgical specimens of HNSCC. A correlation was noted between increased expression
      of IL-1beta and nodal status, as well as increased expression of COX-2 and
      histologic differentiation, clinical stage and nodal status. Increased Slug
      expression was correlated with histologic differentiation and clinical stage.
      Decreased E-cadherin expression was correlated with histologic differentiation
      and nodal status. A significant relationship was observed between IL-1beta and
      COX-2. However, a significant inverse correlation was noted between Slug and E
      cadherin. A significant relationship was observed between increased
      proinflammatory mediator IL-1beta/COX-2 expression and increased EMT marker
      Slug/E-cadherin expression. These results indicate that proinflammatory mediators
      IL-1beta and COX-2 may induce EMT through an increase in Slug and a decrease in E
      cadherin. The present findings suggest that various anti-inflammatory agents
      could be used as an adjuvant treatment modality with anti-cancer chemotherapeutic
      drugs in HNSCC.

PMID- 22993615
TI  - High Dickkopf-1 expression is associated with poor prognosis in patients with
      advanced urothelial carcinoma.
AB  - Although Dickkopf-1 (DKK1) has been demonstrated to be associated with
      tumorigenesis in various types of human tumors, a correlation between DKK1 and
      urothelial carcinoma (UC) has not been reported. In the present study, the
      correlation between DKK1 expression and UC progression was investigated. Seventy
      five UC patients were enrolled. The expression of DKK1 in serum and UC tissue was
      detected by ELISA, real-time PCR and Western blotting. Prognostic significance
      was assessed by using Kaplan-Meier survival estimates and log-rank tests. The
      results showed that serum levels of DKK1 were significantly higher in the UC
      patients with muscle-invasive (p=0.0001) and high-grade tumors (p=0.00001) as
      compared to the controls. A high-serum DKK1 was also associated with poor disease
      free survival in the UC patients (hazard ratio=2.44; 95% CI 1.10-5.40; p=0.028).
      Furthermore, DKK1 was also overexpressed in 93% (41/44) of the UC tissues.
      Therefore, the findings indicate that the expression of DKK1 is associated with
      UC progression.

PMID- 22993616
TI  - siRNA-mediated knockdown of VEGF-A, VEGF-C and VEGFR-3 suppresses the growth and
      metastasis of mouse bladder carcinoma in vivo.
AB  - The growth of solid tumors is highly dependent on the formation of new blood
      and/or lymph vessels. Furthermore, metastases often disperse via newly formed
      blood or lymphatic vessels within the tumor, particularly in the case of
      epithelium-derived tumors. Since vascular endothelial growth factor (VEGF)
      signaling plays a vital role in angiogenesis and lymphangiogenesis, we used the
      small interfering RNA (siRNA) approach to selectively down-regulate VEGF-A, VEGF
      C or VEGF receptor 3 (VEGFR-3) expression in bladder transitional carcinoma cells
      derived from T739 mice in an attempt to suppress tumor growth and metastasis in
      vivo. The synthetic siRNA was introduced into the tumor tissues by in vivo
      electroporation. The knockdown of VEGF-A, VEGF-C and VEGFR-3 expression
      significantly delayed tumor growth and reduced tumor metastasis compared to the
      negative controls. Thus, electroporation-mediated siRNA delivery to block the
      VEGF signaling pathway may provide a novel approach for the treatment or
      prevention of solid tumor growth and metastasis.

PMID- 22993617
TI  - Analysis of differential gene expression by bead-based fiber-optic array in
      growth-hormone-secreting pituitary adenomas.
AB  - Growth-hormone-secreting pituitary adenomas (GHomas) account for approximately
      20% of all pituitary neoplasms. However, the pathogenesis of GHomas remains to be
      elucidated. To explore the possible pathogenesis of GHomas, we used bead-based
      fiber-optic arrays to examine the gene expression in five GHomas and compared
      them to three healthy pituitaries. Four differentially expressed genes were
      chosen randomly for validation by quantitative real-time reverse transcription
      polymerase chain reaction. We then performed pathway analysis on the identified
      differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes.
      Array analysis showed significant increases in the expression of 353 genes and
      206 expressed sequence tags (ESTs) and decreases in 565 genes and 29 ESTs.
      Bioinformatic analysis showed that the genes HIGD1B, HOXB2, ANGPT2, HPGD and BTG2
      may play an important role in the tumorigenesis and progression of GHomas.
      Pathway analysis showed that the wingless-type signaling pathway and
      extracellular-matrix receptor interactions may play a key role in the
      tumorigenesis and progression of GHomas. Our data suggested that there are
      numerous aberrantly expressed genes and pathways involved in the pathogenesis of
      GHomas. Bead-based fiber-optic arrays combined with pathway analysis of
      differentially expressed genes appear to be a valid method for investigating the
      pathogenesis of tumors.

PMID- 22993618
TI  - Quercetin and sulforaphane in combination suppress the progression of melanoma
      through the down-regulation of matrix metalloproteinase-9.
AB  - Malignant melanoma is one of the most common types of cancer in the US and
      worldwide. The epidemiological data suggest that dietary modification may reduce
      the incidence of this disease. Quercetin (3,5,7,3',4'-tetrahydroxyflavone), a
      flavonoid isolated from onion, exhibits anti-oxidant, anti-inflammatory and anti
      cancer effects. D,L-sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane], a
      cruciferous vegetable-derived isomer isolated from broccoli, is highly effective
      in protection against cancer. Matrix metalloproteinases (MMPs), extracellular
      matrix degrading enzymes, are involved in embryogenesis, inflammation,
      angiogenesis and cancer. MMP-9 in particular plays a crucial role in the
      regulation of invasion, tumor growth and metastasis. Previous studies have
      reported that both quercetin and sulforaphane independently reduce tumor growth
      and metastasis in breast, prostate, lung and other types of cancers. However, the
      combined effects of quercetin and sulforaphane on the regulation of tumor growth
      and the mechanism(s) of actions underlying this process have not yet been
      investigated. In the present study, we report for the first time that quercetin
      and sulforaphane in combination inhibit the proliferation and migration of
      melanoma (B16F10) cells more effectively than either compound used alone.
      Moreover, these compounds in combination significantly suppressed melanoma growth
      as compared to their individual use in a mouse model. This combined effect was
      predominantly due to a decrease in MMP-9 expression in the mouse tumors. Taken
      together, our findings revealed that the administration of quercetin and
      sulforaphane in combination rather than alone may be a more effective approach
      for the treatment of malignant melanoma.

PMID- 22993619
TI  - Markers of vascular differentiation, proliferation and tissue remodeling in
      juvenile nasopharyngeal angiofibromas.
AB  - Juvenile nasopharingeal angiofibroma (JNA) is a histologically benign locally
      aggressive tumor characterized by irregular vessels embedded in a fibrous stroma.
      Excessive vascularity results in bleeding complications, and the inhibition of
      angiogenesis is a promising strategy for managing extensive JNA tumors. To better
      characterize the endothelial components of JNA, we aimed to evaluate markers of
      vascular differentiation and proliferation, such as friend leukemia integration-1
      (FLI-1) and endoglin, lymphatic markers, including podoplanin and vascular
      endothelial growth factor receptor 3 (VEGFR3) and its cognate ligand VEGFC, GLUT
      1, a diagnostic marker that discriminates between hemangiomas and vascular
      malformations, and two markers of tissue remodeling, stromelysin 3 (ST3) and
      secreted acid protein rich in cysteine (SPARC). Antigens were assessed
      immunohistochemically in vessels and stromal cells of JNA archival cases (n=22).
      JNA endothelial cells were positive for endoglin, VEGFC and FLI-1, whereas
      podoplanin and VEGFR3 were negative in all cases. Both endothelial cells and
      fibroblasts stained for ST3 and SPARC. GLUT-1 was investigated in JNA cases, in
      infantile hemangiomas (n=123) and in vascular malformations (n=135) as controls.
      JNAs and vascular malformations were GLUT-1-negative, while hemangiomas showed
      positive staining. The presence of markers of endothelial differentiation and
      proliferation highlighted the hyper-proliferative state of JNA vessels. The
      absence of podoplanin and VEGFR3 underscores their blood endothelial cell
      characteristic. The absence of GLUT-1 discriminates JNAs from hemangiomas. ST3
      and SPARC up-regulation in endothelial cells and fibroblasts may contribute to a
      compensatory signaling for controlling angiogenesis. Some of these markers may
      eventually serve as therapeutic targets. Our results may aid in the understanding
      of JNA pathophysiology.

PMID- 22993620
TI  - Comparison of evaluations of hormone receptors in breast carcinoma by image
      analysis using three automated immunohistochemical stainings.
AB  - The aim of this study was to compare the results of immunohistochemistry (IHC)
      assays evaluated by human examiners with the results evaluated by computerized
      image analysis, and to compare the computerized image analysis results among
      three automated IHC assays, namely the BioGenex, Dako and Ventana assays. All
      slides were semiquantitatively evaluated according to the Allred score and J
      score by human examiners. The images were analyzed using MacSCOPE version 2.6 for
      Macintosh according to the H-score and the percentage of positive-stained nuclei
      per area of carcinoma cells (PP) irrespective of the intensity of the stained
      nuclei. The H-score for the estrogen receptor (ER) was significantly correlated
      with the Allred score (P<0.0001) and the PP for the ER was significantly
      correlated with the J-score (P<0.0001), suggesting that the image analysis used
      in the present study is a useful method for the evaluation of ER status. Several
      discrepancies were identified between the Allred score and H-score and between
      the PP and J-score due to the positive-stained cytoplasm area of carcinoma cells
      and/ or the positive-stained nuclei area of non-carcinoma cells, including benign
      epithelial cells, lymphocytes and stromal cells. Accordingly, advances in the
      algorithm of the digitized analyzing system is necessary.

PMID- 22993621
TI  - High ratio of interfollicular CD8/FOXP3-positive regulatory T cells is associated
      with a high FLIPI index and poor overall survival in follicular lymphoma.
AB  - Several studies have highlighted the importance of the microenvironment in the
      behaviour of follicular lymphoma (FL). We conducted an immunohistochemical
      analysis to assess the role of different cell subpopulations, i.e. CD8, CD68 and
      forkhead box protein P3 (FOXP3)-positive regulatory T cells (Treg cells) in 84
      lymph nodes of 58 patients with FL (58 at diagnosis, 26 at relapse). Since the
      overall effect of Tregs is considered to depend on their number in relation to
      CD8(+) effector T cells, we determined the corresponding ratio for each patient
      and correlated the results with clinical parameters. The interfollicular
      CD8/FOXP3(+) cell ratio was significantly higher in patients with histological
      grade 3 tumours (2.04 vs. 1.63) and with a high risk FLIPI index (2.99 vs. 1.53)
      compared to those with grade 1-2 tumours or a low-intermediate FLIPI index.
      Similar results were obtained for the follicular CD8(+)/FOXP3(+) cell ratio. The
      interfollicular CD8/FOXP3 ratio was found to have prognostic value [a 5-year
      overall survival (OS) of 82 vs. 59% for a ratio of +/-1.68]. In addition, an
      interfollicular FOXP3(+) cell number of more than 86 cells/mm(2) was correlated
      with a more favourable outcome (p=0.03). When patients at diagnosis and relapse
      were compared, a significant difference (p=0.05) in the localization
      (interfollicular vs. intrafollicular) of FOXP3(+) cells was observed. The
      CD8/FOXP3 ratio in the interfollicular areas was significantly different (1.66 at
      diagnosis vs. 2.2 at relapse, p=0.05). The presence of a small number of FOXP3(+)
      cells with a high CD8/FOXP3 ratio is probably the indicator of an active immune
      response during tumour development, with lymphoma cells acting as targets or
      bystanders.

PMID- 22993622
TI  - Absence of the K303R estrogen receptor alpha mutation in breast cancer patients
      exhibiting different responses to aromatase inhibitor anastrozole neoadjuvant
      treatment.
AB  - Aromatase inhibitors, such as anastrozole, are established in the treatment of
      hormone-dependent breast cancer. However, approximately 20% of patients treated
      with anastrozole do not respond, and it remains impossible to accurately predict
      sensitivity. Thus, novel markers to predict response are required. The K303R
      estrogen receptor (ER)alpha mutation confers resistance to tamoxifen treatment.
      Moreover, K303R-expressing MCF-7 cells, transfected with an aromatase expression
      vector and stimulated with androstenedione (an aromatase substrate), were found
      to be resistant to the inhibitory effect of anastrozole. The aim of this study
      was to verify whether the presence of the K303R ERalpha mutation is associated
      with response to 3-month neoadjuvant treatment with anastrozole (Arimidex) in a
      cohort of post-menopausal breast cancer patients. Of 37 patients with ER(+)
      tumors, 19 showed a clinical response to anastrozole and 18 were resistant.
      Biopsies were obtained from tumors responding to the therapy or from non
      responding tumors. None carried the K303R ERalpha mutation. To our knowledge,
      this is the first study to search for K303R ERalpha mutations in tumors
      clinically responsive or resistant to an aromatase inhibitor. Lack of the
      mutation leads us to believe that this mutation has in vivo biological
      significance in only a subset of breast cancers.

PMID- 22993623
TI  - Schedule-dependent synergistic effect of rituximab on methotrexate chemotherapy
      against lymphoma of the central nervous system.
AB  - We hypothesized that methotrexate (MTX) normalizes the increased permeability of
      the blood-tumor barrier and thus reduces the accessibility of rituximab (RTX) to
      central nervous system (CNS) lymphoma. Here, we evaluated the combinational
      treatment capability of RTX and MTX using an alternative treatment schedule
      against CNS lymphoma. We developed a CNS lymphoma animal model that closely
      mimics the morphological and molecular characteristics of human CNS lymphoma by
      injecting Raji human Burkitt lymphoma cells into the brains of immune-compromised
      mice and tested a novel combinational treatment schedule by which penetration of
      RTX was not influenced by MTX administration. RTX was conjugated with Alexa Fluor
      680, and its distribution in the brain was analyzed by in vivo imaging. When MTX
      treatment was followed by a 3-day post RTX administration, RTX was scarcely
      distributed in the brain, and there were only modest statistically insignificant
      therapeutic effects compared with the control mice which received sham
      injections. In contrast, RTX administration followed by a 3-day post MTX
      treatment showed significantly increased distribution of RTX and significantly
      reduced tumor volume in the brain. Collectively, our data demonstrate that RTX
      can be successfully combined with MTX using an alternative treatment schedule
      that allows increased distribution of RTX in CNS lymphoma.

PMID- 22993624
TI  - Silencing STAT3 with short hairpin RNA enhances radiosensitivity of human
      laryngeal squamous cell carcinoma xenografts in vivo.
AB  - Short hairpin RNA (shRNA) targeting signal transducer and activator of
      transcription 3 (STAT3) potentiate the radiosensitivity of human laryngeal
      squamous carcinoma cells in vitro. In the present study, we investigated the
      inhibitory effect of STAT3 shRNA plus radiotherapy on nude mouse laryngeal
      squamous cell carcinoma xenografts. The xenotransplanted tumors were treated with
      STAT3 shRNA, with or without radiation, following a planned scheme. The
      inhibition rate for tumor growth was calculated and the tumor growth curve was
      plotted. In addition, the expression of p-STAT3, B cell lymphoma 2 (Bcl-2), p53,
      vascular endothelial growth factor (VEGF) protein and intratumoral microvessel
      density (MVD) was determined by immunohistochemistry. Flow cytometry was used to
      detect the rate of cell apoptosis. The results revealed that STAT3 shRNA
      transfection plus radiotherapy significantly minimized tumor volume and increased
      the rate of tumor inhibition. p-STAT3 protein expression and intratumoral MVD
      were observed to be down-regulated, whereas apoptosis was increased. There was a
      positive correlation between the expression of p-STAT3 and Bcl-2, and also
      between the expression of p53 and VEGF, and MVD. These findings indicate that
      STAT3 shRNA potentiate the radiosensitivity of laryngeal carcinoma xenografts in
      vivo by regulating downstream signaling proteins in the STAT3 pathway.

PMID- 22993625
TI  - Identification of a set of genes associated with response to interleukin-2 and
      interferon-alpha combination therapy for renal cell carcinoma through genome-wide
      gene expression profiling.
AB  - Interleukin (IL)-2 and interferon (IFN)-alpha combination therapy for metastatic
      renal cell carcinoma (RCC) improves the prognosis for a subset of patients, while
      some patients suffer from severe adverse drug reactions with little benefit. To
      establish a method to predict responses to this combination therapy
      (approximately 30% response rate), the gene expression profiles of primary RCCs
      were analyzed using an oligoDNA microarray consisting of 38,500 genes or ESTs,
      after enrichment of the cancer cell population by laser micro-beam
      microdissection. The analysis of 10 responders and 18 non-responders identified
      24 genes that exhibited significant differential expression between the two
      groups. In addition, the patients whose tumors did not express HLA-DQA1 or HLA
      DQB1 molecules demonstrated poor clinical response. Exclusion of patients with
      tumors lacking either of these two genes is likely to improve the response rate
      to IL-2 and IFN-alpha combination therapy from 30 to 67%, indicating that a
      simple pretreatment test provides useful information with which to subselect
      patients with renal cancer in order to improve the efficacy of this treatment and
      reduce unnecessary medical costs.

PMID- 22993626
TI  - Serum harvested from heifers one month post-zeranol implantation stimulates MCF-7
      breast cancer cell growth.
AB  - Breast cancer is a serious disease in the US. Numerous risk factors have been
      linked to this disease. The safety of using growth promoters, such as zeranol,
      remains under debate due to the lack of sufficient in vitro and in vivo evidence.
      Using CellTiter 96(TM) Aqueous Non-Radioactive Cell Proliferation assay, real
      time PCR and Western blot analysis, we evaluated the effects of sera harvested
      from experimental and control heifers before and after one month of zeranol
      implantation on the growth of human breast cancer cell line MCF-7 as well as the
      involved mechanisms. We found that sera harvested from the heifers following one
      month of zeranol implantation were more mitogenically potent in stimulating the
      proliferation of MCF-7 cells when compared to sera harvested from the same
      heifers before zeranol implantation and the control heifers. Further
      investigation found that dextran-coated charcoal suppressed the stimulating
      effect of the sera on MCF-7 cell growth. The mechanisms involved in the MCF-7
      cell proliferation stimulated by zeranol-containing sera may include up
      regulation of cyclin D1 and down-regulation of p53 and p21 expression at the mRNA
      and protein levels in the cells. The results suggest that the consumption of beef
      products containing biologically active residues of zeranol or its metabolites is
      a risk linked to breast cancer development. Further investigation is required in
      order to clarify this critical issue.

PMID- 22993627
TI  - Association of genetic variants with myocardial infarction in Japanese
      individuals with or without metabolic syndrome.
AB  - The etiology of metabolic syndrome (MetS) is highly complex, with both genetic
      and environmental factors being thought to play an important role. Although MetS
      has been recognized as a risk factor for myocardial infarction (MI), the genetic
      risk for MI in individuals with or without MetS has remained uncharacterized. We
      examined a possible association of genetic variants with MI in individuals with
      or without MetS separately. The study population comprised 4,424 individuals,
      including 1,918 individuals with MetS (903 subjects with MI and 1,015 controls)
      and 2,506 individuals without MetS (499 subjects with MI and 2,007 controls). The
      150 polymorphisms examined in the present study were selected by genome-wide
      association studies of MI and ischemic stroke with the use of Affymetrix GeneChip
      Human Mapping 500K Array Set. Initial screening by the Chi-square test revealed
      that the C->T polymorphism (rs1794429) of LRPAP1, the A->G polymorphism
      (rs12373237) of LAMA3 and the A->G polymorphism (rs3782257) of NCOR2 were
      significantly (false discovery rate of <0.05) associated with MI for individuals
      with MetS, and that the C->G polymorphism (rs13051704) of TFF1 was significantly
      related to MI for individuals without MetS. Subsequent multivariable logistic
      analysis with adjustment for covariates revealed that rs1794429 of LRPAP1
      (recessive model; P=0.0218; odds ratio=0.71) and rs3782257 of NCOR2 (dominant
      model; P=0.0057; odds ratio=1.94) were significantly associated with MI among
      individuals with MetS, and that rs13051704 of TFF1 (additive model; P=0.0100;
      odds ratio=0.55) was significantly associated with MI among individuals without
      MetS. The genetic variants that confer susceptibility to MI differ between
      individuals with or without MetS. Stratification of subjects according to the
      presence or absence of MetS may thus be important for personalized prevention of
      MI based on genetic information.

PMID- 22993628
TI  - Relationship between the benefits of suplatast tosilate, a Th2 cytokine
      inhibitor, and gene polymorphisms in children with bronchial asthma.
AB  - Although currently available antiasthmatic drugs are effective for many patients
      with bronchial asthma, some patients do not respond well to medications or
      exhibit more frequent adverse effects compared to other patients. Antiasthmatic
      treatment should be tailored individually according to the predispositions and
      pathophysiological conditions of patients. No reports have been made concerning
      the relationships between the effects of Th2 cytokine inhibitors and gene
      polymorphisms. The present study was therefore performed to investigate the
      relationships between gene polymorphisms known to be involved in allergy and
      cytokine production in peripheral blood mononuclear cells and the clinical
      efficacy of suplatast tosilate, a Th2 cytokine inhibitor, to clarify factors
      determining responses to treatment. A total of 20 children were enrolled in the
      study. The children were enrolled in a run-in period of 2 weeks and then received
      suplatast tosilate orally for 8 weeks. The children or their parents were
      instructed to keep an asthma diary to record changes in signs/symptoms of
      bronchial asthma before and after treatment. Concentrations of interferon (IFN)
      gamma and interleukin (IL)-4 in the supernatant were determined using ELISA
      methods. Using the invader assay method, the genotypes of polymorphisms of the
      genes were determined. Treatment with suplatast tosilate was more effective in
      children without the -444 A/C polymorphism of the LTC4 synthase gene and in
      children without the IL-13 variant R110Q. In children who responded well,
      production of IFN-gamma was significantly increased after treatment. In this
      study, responses to suplatast tosilate were associated with SNPs of the LTC4
      synthase and IL-13 gene as well as change in the production of IFN-gamma before
      and after drug administration.

PMID- 22993629
TI  - Antiviral effects of dehydroascorbic acid.
AB  - IN THE PRESENT STUDY, DEHYDROASCORBIC ACID INHIBITED THE MULTIPLICATION OF
      VIRUSES OF THREE DIFFERENT FAMILIES: herpes simplex virus type 1 (HSV-1),
      influenza virus type A and poliovirus type 1. Although dehydroascorbic acid
      showed some cytotoxicity at higher concentrations, the observed antiviral
      activity was not the secondary result of the cytotoxic effect of the reagent, as
      the inhibition of virus multiplication was observed at reagent concentrations
      significantly lower than those resulting in cytotoxicity. Characterization of the
      mode of the antiviral action of dehydroascorbic acid against HSV-1 revealed that
      the addition of reagent at any time post infection inhibited the formation of
      progeny infectious virus in the infected cells, and a one-step growth curve
      showed that the addition of reagent allowed formation for an additional 2 h, but
      then almost completely suppressed it. These results indicate that the reagent
      inhibits HSV-1 multiplication after the completion of viral DNA replication,
      probably at the step of the envelopment of viral nucleocapsids at the Golgi
      apparatus of infected cells.

PMID- 22993630
TI  - Hepatic arterial infusion chemotherapy for post-operative liver metastases from
      pancreatic cancer in a patient with leukocytopenia: A case report.
AB  - Here, we present a case of post-operative liver metastases from pancreatic head
      cancer in a patient with leukocytopenia, who was safely treated by hepatic
      arterial infusion (HAI) chemotherapy consisting of gemcitabine and 5-FU. The
      patient was a 61-year-old woman who underwent pancreaticoduodenectomy for
      pancreatic head cancer, but was found to be an unsuitable candidate for adjuvant
      systemic chemotherapy due to the presence of leukocytopenia. Five months after
      surgery, a follow-up CT revealed two liver metastases. Intravenous systemic
      chemotherapy was also contraindicated due to the leukocytopenia. In the apparent
      absence of recurrence, excepting the liver metastases, we decided to administer
      HAI chemotherapy, which had already been administered following the curative
      surgery. HAI chemotherapy has been shown to be associated with a lower incidence
      of systemic side effects. Gemcitabine at a dose of 400 mg was administered via a
      bedside pump and infused over 30 min. After gemcitabine infusion, 250 mg of 5-FU
      was infused continuously over 24 h from days 1 to 5. This comprised 1 cycle of
      therapy. The treatment cycles were continued biweekly. After 10 cycles without
      severe side effects, it was found that though the size of the metastatic tumors
      was not reduced, tumor vascularity was. However, after the 13th treatment cycle,
      local recurrence and lymph node metastases were detected. By this time, the
      patient had recovered from the leukocytopenia, and could thus be administered
      systemic chemotherapy. In conclusion, HAI chemotherapy is useful and safe for the
      treatment of malignancies confined to the liver, even in cases where the patient
      is in a reduced physical condition.

PMID- 22993631
TI  - Effect of the interaction between the amount and duration of alcohol consumption
      and tobacco smoking on the risk of esophageal cancer: A case-control study.
AB  - The effects of alcohol consumption and tobacco smoking on the prevalence of
      esophageal cancer vary considerably by country, race and lifestyle. Few data
      exist on the effect of the interaction between the amount and duration of alcohol
      consumption and tobacco smoking on the incidence of esophageal cancer. In this
      case-control study, the cases included patients with histologically confirmed
      esophageal squamous cell carcinoma (ESCC) younger than 60 years of age and
      recruited between January 1, 2002 and December 31, 2006. The controls had no
      abnormality during a medical checkup. A total of 835 pairs were created by
      pairing each case to a gender- and age-matched control. Conditional logistic
      regression analysis was used to estimate adjusted odds ratios (ORs) and 95%
      confidence intervals. Univariate conditional logistic regression analyses
      revealed that the ORs according to both duration of alcohol consumption and
      tobacco smoking increased monotonically. Alcohol consumption and tobacco smoking
      may have a synergistic effect on the incidence of ESCC. Conditional logistic
      regression analysis using a forward stepwise selection procedure revealed that
      the incidence of ESCC was associated with the duration of tobacco smoking, the
      interaction between the amount and duration of alcohol consumption, and a family
      history of cancer. In particular, groups with a long duration of alcohol
      consumption and high alcohol intake had much higher ORs than those with short
      duration and low intake, which highlights the importance of the interaction
      between the amount and duration of alcohol intake. This study confirmed the
      significance of the interaction between alcohol consumption and tobacco smoking
      in esophageal cancer. This interaction between amount and duration is an accurate
      indicator for estimating the risk of esophageal cancer attributable to alcohol
      consumption and tobacco smoking. These findings suggest that decreasing the
      number of young and middle-aged drinkers and smokers will reduce the incidence of
      esophageal cancer.

PMID- 22993632
TI  - A new experimental approach is required in the molecular analysis of intestinal
      neuronal dysplasia type B patients.
AB  - Intestinal neuronal dysplasia type B (INDB) is characterized by the malformation
      of the parasympathetic submucous plexus of the gut. It is generally accepted that
      INDB has a genetic basis, and several genes produce an INDB-like phenotype in
      mice when disrupted, such as EDNRB. However, no mutations associated with this
      disease have been identified in several series analysed. In the present studu, we
      sought to determine whether the EDNRB/EDN3 signalling pathway plays a role in the
      pathogenesis of INDB in humans. Denaturing high performance liquid chromatography
      (dHPLC) techniques were employed to screen the EDNRB and EDN3 coding regions in
      23 INDB patients. In addition, association studies were performed on these genes
      with single nucleotide polymorphisms strategically selected and genotyped by
      TaqMan technology. Although several novel variants were detected in both genes,
      none of these variants appeared to play a functional role in protein function or
      expression. Our results indicate that additional screening of other candidate
      genes in larger patient series is required to elucidate the molecular basis of
      INDB. Additionally, the systematic lack of positive results in the screening of
      candidate genes for INDB reported in the literature, together with our results,
      leads us to propose that INDB may alternatively arise as a consequence of gain of
      function mutations in genes related to enteric nervous system development.
      Therefore, the use of different molecular approaches, such as screening for
      genetic duplication or enhancer mutations, is recommended for future studies on
      the genetic basis of INDB.

PMID- 22993633
TI  - Salvage chemotherapy for hormone-refractory prostate cancer: Association of
      Adriamycin and ifosfamide.
AB  - Prostate carcinoma is the most common cancer in men. Hormone-resistance is the
      natural history of this metastatic disease and requires the use of docetaxel as
      the standard chemotherapy. At present, there is no approved second-line
      treatment. Here, we report a combination of treatment with Adriamycin and
      ifosfamide in a series of 7 relatively young patients with an average age of 57
      years at the time of diagnosis. Chemotherapy was administered over 3 days with
      the following schedule: 20 mg/m(2) Adriamycin per day and 1-1.5 mg/m(2)
      ifosfamide per day, in association with Uromitexan. Treatment was repeated every
      3 weeks. Three biological responses, one CT scan response, one bone scan response
      and two CT scan stabilizations, were obtained. Mean survival following this
      combination was 6.6 months, and over 26 months after first-line chemotherapy.
      Tolerance was good with the use of granulocyte-colony stimulating factors. Our
      observations clearly show that the use of this type of salvage therapy for
      relatively young patients in good physical condition should be further assessed
      in a clinical trial, particularly when different lines of chemotherapy are
      required.

PMID- 22993634
TI  - Genomic and in vivo evidence of synergy of a herbal extract compared to its most
      active ingredient: Rabdosia rubescens vs. oridonin.
AB  - Rabdosia rubescens is a herbal root extract of traditional Chinese medicine (TCM)
      used to treat inflammatory diseases and oral cancers. A key principle of TCM is
      that multiple ingredients in a plant extract are more effective and less toxic
      than a single purified active ingredient or a purified drug derived from a plant
      product. Rabdosia rubescens extract (RRE) contains terpenoids and flavonoids, but
      the most active ingredient within the extract attributed to the inhibition of
      cancer is the kaurene diterpene, oridonin. In order to research synergy with a
      complete plant extract, the effects of RRE on the inhibition of prostate cancer
      cell proliferation were compared to the effects of pure oridonin alone in vitro.
      Three groups of 8 SCID mice bearing human prostate cancer xenografts (LAPC-4)
      were administered either RRE containing 0.02 mg/g oridonin, pure oridonin at a
      dose of 0.02 mg/g, or pure oridonin at a dose of 0.1 mg/g, by gavage for 5
      days/week for 4 weeks. RRE and pure oridonin at 0.1 mg/g inhibited tumor growth
      to a similar extent, while oridonin at a dose of 0.02 mg/g did not. Therefore, in
      comparison to RRE, five times more pure oridonin was required to obtain
      equivalent prostate xenograft growth inhibition. Since the nuclear factor-kappaB
      signaling pathway and inflammation are implicated in prostate carcinogenesis,
      gene microarray analysis was conducted and demonstrated activation of genes by
      RRE that was not evident with oridonin treatment alone. This study demonstrated
      that genomic methods and xenograft studies are capable of demonstrating the
      benefits of the synergy of whole plant extracts rather than active ingredients
      isolated and purified as drugs.

PMID- 22993635
TI  - Age-related changes in peripheral blood counts in humans.
AB  - Anaemia has become a common concern in geriatric health. Since its prevalence
      varies quite significantly among different groups depending on factors such as
      ethnicity, lifestyle or fitness, the appropriateness of the current WHO
      definition of anaemia in the elderly may be questioned. We evaluated peripheral
      blood parameters from 1,724 individuals (908 women aged 18-101 years and 816 men
      aged 18-96 years), who were treated at the University of Heidelberg Medical
      Center with no known haematological history. Patients with a known malignant
      haematological or oncological disease or with chronic infection or inflammation
      were excluded. Patients with disorders affecting the kidneys, thyroid or stomach,
      as well as patients with a bleeding history, haemolysis or who had been
      previously diagnosed with anaemia were excluded from the study. Average
      haemoglobin levels for men beyond the age of 70 and for women beyond the age of
      80 were found to fulfill the WHO criteria for the diagnosis of anaemia. While in
      our cohort ~20% of men and women between 60-69 years of age were by definition
      anaemic, these numbers steadily increased to 63% in females and 76% in males
      beyond the age of 90. Based on the results of our study and in accordance with
      the literature on this topic, we suggest age-adjusted criteria for the diagnosis
      of anaemia in the elderly in conjunction with a geriatric assessment.

PMID- 22993636
TI  - Clinical application of positron emission tomography in designing radiation
      fields in non-small cell lung cancer patients.
AB  - There is significant interest in incorporating positron emission tomography (PET)
      into radiation therapy planning, although limited data exist that separately
      consider its diagnostic accuracy with respect to the primary tumor, hilum and
      mediastinum. This study evaluates the accuracy of PET planning by region of
      interest. Between January 2003 and July 2005, 351 patients with a pre-operative
      PET study underwent surgical resection. Of this population, 257 (73%) patients
      with a diagnosis of non-small cell lung cancer were evaluated. PET study findings
      regarding the suspected primary tumor site, ipsilateral hilum and mediastinum
      were correlated with surgical pathology for determination of accuracy,
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV). The accuracy of the primary site (95%), ipsilateral hilum (80%) and
      mediastinum (84%) was relatively high. The NPV of the ipsilateral hilum and
      mediastinum was also high (92 and 86%, respectively). However, the PPV of the
      ipsilateral hilum (31%) and mediastinum (75%) was lower. PET accuracy evaluating
      bronchoalveolar primary tumors was lower vs. other histologies (86 vs. 96%,
      p=0.02), although there was no difference with regard to the hilum or
      mediastinum. PET scanning may be an important tool in designing radiation
      treatment fields for lung cancer when combined with other imaging modalities.
      However, caution must be exercised when evaluating lymph node regions, as the PPV
      is not as high for the ipsilateral hilum and mediastinum as for the primary
      tumor. The NPV is high for nodal regions and may help with the exclusion of large
      treatment volumes in selected cases.

PMID- 22993637
TI  - Association between common genetic variants in pre-microRNAs and the
      clinicopathological characteristics and survival of gastric cancer patients.
AB  - Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) have been
      shown to be associated with susceptibility to several types of human cancer. We
      evaluated the association between three SNPs (rs11614913, rs2910164 and
      rs3746444) in pre-miRNAs (miR-196a2, miR-146a and miR-499) and various
      clinicopathological characteristics, including CpG island hypermethylation (CIHM)
      status and overall survival in gastric cancer (GC) patients. rs11614913 (T>C),
      rs2910164 (C>G) and rs3746444 (A>G) SNPs were genotyped in 127 GC patients. CIHM
      of p14, p16, DAP-kinase and CDH1 genes was determined by methylation-specific
      polymerase chain reaction in the cancer tissues. A significant marginal
      association was found between the rs11614913 CC genotype and polypoid or elevated
      type morphology in early-stage GC (OR=6.29, 95% CI 1.18-33.47, p=0.03). The
      rs2910164 CC and CG genotypes were associated with increased susceptibility to
      CIHM of DAP-kinase (CC+CG, OR=5.48, 95% CI 1.30-23.10, p=0.02; CC, OR=6.93, 95%
      CI 1.37-35.02, p=0.02; CG, OR=4.24, 95% CI 0.87-20.78, p=0.07). The 11614913 TT
      and TC genotypes were associated with a higher number of CIHM (no. of CIHM 0-1
      vs. 2-4; TT+TC, OR=3.67, 95% CI 0.98-13.72, p=0.05; TC, OR=4.08, 95% CI 1.04
      15.97, p=0.04). When the subjects were divided according to age group, the
      combined rs11614913 TT+TC genotype tended to be associated with worse overall
      survival than the CC genotype in patients younger than 65 years of age (p=0.05).
      The combined rs2910164 CG+GG genotype also tended to be associated with worse
      overall survival than the CC genotype in the same age group (p=0.09). It appears
      that rs11614913 and rs2910164 SNPs in pre-miRNAs (miR-196a2 and miR-146a) affect
      the clinicopathological characteristics of GC, including its morphological
      appearance, CIHM status and overall survival.

PMID- 22993638
TI  - Hepatocyte-protective and anti-oxidant effects of rifampicin on human chronic
      hepatitis C and murine acute hepatocyte disorder.
AB  - Rifampicin (RFP) is a semisynthetic antibiotic derived from the rifamycins and is
      one of the most commonly used pharmaceutical compounds worldwide in the treatment
      of tuberculosis. We previously reported that low-dose and long-term oral
      administration of RFP to 6 hepatitis C virus-related liver cirrhosis patients who
      were at high risk for presenting with hepatocellular carcinoma (HCC) resulted in
      a marked suppression of the occurrence of HCC without showing an adverse effect.
      The underlying mechanism was found to be due to the anticancer effect based on
      the potent anti-angiogenic properties of RFP. The present study revealed that RFP
      has an additional hepatocyte-protective effect by lowering the release of hepatic
      enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in
      chronic hepatitis C patients. Experimentally, we were able to show that RFP had
      hepatocyte-protective effects in acute hepatocyte disorder models of mice and
      rats induced by concanavalin A and by D-galactosamine, respectively: RFP
      significantly prevented an increase in the levels of ALT, AST and lactate
      dehydrogenase in these animal models. In addition, we found that RFP had a strong
      anti-oxidant action which was approximately three times stronger than the action
      of silibinin, an anti-inflammatory agent of human hepatic stellate cells,
      implicating that the hepatocyte-protective effects of RFP are mediated by its
      anti-oxidant activity. These results reveal that oral administration of RFP
      exerts not only a prophylactic effect on the occurrence or recurrence of HCC for
      an extensive period of time, but also exerts hepatocyte-protective effects on
      both human chronic hepatitis C and acute hepatocyte disorder in rodent models,
      and the anti-oxidant activity of RFP is implicated to participate in the latter
      effects.

PMID- 22993639
TI  - Increased expression but not sensitivity to Fas/CD95 in glioblastoma cells
      depleted of mitochondrial DNA.
AB  - Mitochondria and Fas (CD95) play a role in tumorigenicity and apoptosis. In the
      present study, the functional relationship of mitochondria to Fas in mediating
      apoptosis was investigated. Glioblastoma cells (DBTRGO5MG, U87) were depleted of
      mitochondrial DNA (mtDNA) by treatment with ethidium bromide (Rho(-) cells).
      Compared to Rho(+) cells, Rho(-) cells showed enhanced expression of Fas at the
      cell surface. Indeed, when Rho(+) cells were treated with mitochondrial
      respiratory chain complex inhibitors, Fas cell surface expression was noted to
      increase in a similar fashion to the depletion of mtDNA in both cell lines.
      However, when cells were evaluated for sensitivity to apoptosis using Fas
      engagement, there was no difference between the Rho(+) and Rho(-) cells in either
      cell line. By contrast, sensitivity to the cytotoxic agent cis-diammine
      dichloroplatinum (cisplatin) was markedly increased in the Rho(-) cells, which
      expressed higher levels of cell surface Fas. Expression of Fas is increased with
      the depletion of mtDNA and respiratory complex inhibitors. However, this increase
      in expression does not necessarily translate to an increase in sensitivity to Fas
      engagement, although there is an increase in the sensitivity of depleted cells to
      cytotoxic agents such as cisplatin.

PMID- 22993640
TI  - Influence of elastin-derived peptides on metalloprotease production in
      endothelial cells.
AB  - Matrix metalloproteases (MMPs) are a family of zinc-dependent endopeptidases that
      degrade extracellular matrix proteins. MMP-1 and MMP-2 are produced by
      endothelial cells and are involved in specific vascular pathologies, including
      atherosclerosis and aortal aneurysm. One of the most important differences
      between these two metalloproteases is the possibility of hydrolysis of elastin
      and collagen type IV by MMP-2, but not by MMP-1. Elastin-derived peptides are
      generated as a result of the degradation of elastin fibers. The aim of our study
      was to compare the production of MMP-1 and MMP-2 in cultured human arterial
      endothelial cells derived from vascular pathologies localized at three different
      sites, the coronary artery, iliac artery and aorta, measured as their
      concentration in cell culture medium. The second aim was to evaluate the
      influence of kappa-elastin (at concentrations 0.1, 0.4, 1.0, 2.5 or 5.0 MUg/ml)
      on the production of the evaluated metalloproteases in three endothelial cell
      lines. The production of MMP-1 was statistically significantly greater in
      endothelial cells derived from the aorta compared to that in the endothelium
      obtained from the coronary and iliac arteries. There were no statistically
      significant differences in the production of MMP-2 among the endothelial cell
      lines tested. The addition of kappa-elastin at all evaluated concentrations did
      not statistically significantly influence the concentration of MMP-1 in the
      cultured coronary artery endothelium. Furthermore, no statistically significant
      differences were observed in the cultured iliac artery endothelium. In the
      cultured endothelium derived from the aorta, kappa-elastin at concentrations of
      0.1 and 0.4 MUg/ml significantly increased the amount of MMP-1.

PMID- 22993641
TI  - Reduced Rank Ridge Regression and Its Kernel Extensions.
AB  - In multivariate linear regression, it is often assumed that the response matrix
      is intrinsically of lower rank. This could be because of the correlation
      structure among the prediction variables or the coefficient matrix being lower
      rank. To accommodate both, we propose a reduced rank ridge regression for
      multivariate linear regression. Specifically, we combine the ridge penalty with
      the reduced rank constraint on the coefficient matrix to come up with a
      computationally straightforward algorithm. Numerical studies indicate that the
      proposed method consistently outperforms relevant competitors. A novel extension
      of the proposed method to the reproducing kernel Hilbert space (RKHS) set-up is
      also developed.

PMID- 22993642
TI  - A Tetrapyrrole Macrocycle Displaying a Multielectron Redox Chemistry and Tunable
      Absorbance Profile.
AB  - Porphyrins are attractive chromophores for incorporation into light harvesting
      devices. Some of the most efficient porphyrin derivatives in this regard are
      synthetically complex platforms with specially tailored electronic properties.
      This work details the unique geometric and electronic structure of the phlorin
      framework. X-ray crystallography and NMR spectroscopy demonstrate that unlike
      typical tetrapyrrole macrocycles, the phlorin is not aromatic. These unusual
      electronics are manifest in distinct photophysical and redox properties, as the
      phlorin displays a rich multielectron redox chemistry. The phlorin also displays
      an intriguing supramolecular chemistry and can reversibly bind up to two
      equivalents of fluoride in cooperative fashion. Accordingly, this synthetically
      accessible sensitizer displays a rich multielectron redox chemistry, excellent
      spectral coverage and an intriguing anion binding chemistry that distinguishes
      this system from more commonly studied porphyrinoids.

PMID- 22993643
TI  - Effects of systemic tadalafil on skin flap survival in rats.
AB  - OBJECTIVE: Phosphodiesterase-5 inhibitors, used to increase penile blood flow in
      erectile dysfunction patients, have recently been postulated to increase blood
      flow and flap survival in cutaneous flaps based on random blood supply. This
      study aims to investigate the phosphodiesterase-5 inhibitor tadalafil,
      administered orally, on random flap survival. METHODS: Modified McFarlane flaps
      measuring 8 cm * 2.5 cm were raised on the backs of 37 male Sprague-Dawley rats.
      Rats received were divided into a control group, a low-dose group (10 mg/kg
      tadalafil), and a high-dose group (20 mg/kg tadalafil). Treatment doses were
      administered once preoperatively and every 24 hours postoperatively for a total
      of 7 doses. On postoperative day 7 and 14, the area of flap survival was
      calculated and compared. RESULTS: All rats survived and thrived throughout the
      experimental period. Control group rats showed an average flap survival of 77% +/
      11% at 7 days and 77% +/- 9% at 14 days. Low-dose-group rats showed an average
      flap survival of 82% +/- 10% at 7 days (P=0.21), and 81% +/- 12% at 14 days
      (P=0.41). High-dose group rats showed an average flap survival of 81% +/- 11% at
      7 days (P = 0.45) and 80% +/- 12% at 14 days (P = 0.53). Statistical analysis was
      performed using the Mann-Whitney test. CONCLUSIONS: Our results indicate a trend
      toward increased random-pattern flap survival with both high- and low-dose oral
      tadalafil in a rat model. Because this trend did not achieve statistical
      significance, further studies are warranted.

PMID- 22993644
TI  - Prognostication for body contouring surgery after bariatric surgery.
AB  - OBJECTIVE: Body contouring surgery has become a steadily increasing part of
      weight loss treatment in the population of patients electing to undergo bariatric
      surgery. This study aims to elicit factors that can be used to prognosticate
      which bariatric surgery patients will choose to undergo body contouring
      procedures. METHODS: A database of 381 patients who underwent gastric bypass
      surgery between August 2002 and December 2005 was retrospectively reviewed. All
      patients with subsequent body contouring surgery (group I) were identified and
      compared with those without it (group II). Variables studied were age, gender,
      preoperative excess body weight, percent excess weight loss at 6 and 12 months,
      preoperative body mass index, and change in body mass index at 6 and 12 months.
      RESULTS: We identified 24 patients for group I and 168 patients for group II.
      Group I was significantly younger with a mean age of 36 +/- 9 years than group II
      with a mean age of 41 +/- 10 years (P = .023). Change in body mass index was
      significantly greater in group I with changes of 16.1 +/- 4 and 13.82 +/- 3 (P =
      .001) at 6 months and changes of 21.4 +/- 6.6 and 17.39 +/- 4.6 (P < .0001) at 12
      months in group I and group II, respectively. Lastly, the percent excess weight
      loss at 12 months was significantly greater in group I with a mean percent excess
      weight loss of 70.1 +/- 13.3 than in group II with a mean percent excess weight
      loss of 62 +/- 16.6 (P = .0052). CONCLUSIONS: Age, change in body mass index at 6
      and 12 months, and percent excess weight loss at 12 month follow-up were useful
      predictive factors to determine which bariatric surgery patients ultimately
      underwent body contouring procedures.

PMID- 22993645
TI  - Mental and physical impact of body contouring procedures on post-bariatric
      surgery patients.
AB  - OBJECTIVE: The rapid rate of weight loss following bariatric surgery leads to
      areas of excessive skin that can cause physical ailments and distortion of body
      image. Dissatisfaction with the excessive skin can lead patients to seek plastic
      surgery. This study aims to assess the changes in mental and physical quality of
      life after body contouring procedures in the post-bariatric surgery population.
      METHODS: In this cross-sectional study, the 36-Item Short Form Health Survey was
      given to 104 patients divided into 4 groups consisting of a control group, obese
      patients, post-bariatric surgery patients, and post-bariatric and -body
      contouring surgery patients. Scores from each survey question were individually
      averaged, scaled, and converted to the corresponding 8 scales that make up the 36
      Item Short Form Health Survey. Scale comparisons were accomplished by analysis of
      variance and t test. RESULTS: Compared with the obese group, both post-bariatric
      surgery patients and post-body contouring surgery patients had improved quality
      of life. When comparing the post-body contouring and post-bariatric surgery
      patients, the post-body contouring group did not show significant quality of life
      improvement and actually scored significantly lower in 2 measures, Role Emotional
      and Social Functioning, indicating a decreased mental component of quality of
      life. When compared with the control group, the post-body contouring surgery
      group had statistically significant lower scores in 6 of the 8 scales.
      CONCLUSIONS: The functional impairment caused by excessive skin following massive
      weight loss interferes with quality of life. Patients electing to have body
      contouring after bariatric surgery show decreased quality of life even after
      plastic surgery compared to those patients who do not.

PMID- 22993646
TI  - Long-term effects of the "Heidelberg Model of Music Therapy" in patients with
      chronic tinnitus.
AB  - OBJECTIVE: The "Heidelberg Model of Music Therapy for Chronic Tinnitus" is a
      manualized short term treatment (nine 50-minutes sessions of individualized
      therapy on five consecutive days). It has proven to be efficient in reducing
      tinnitus symptoms in the short run. Now the long-term impact of the treatment
      after up to 5.4 years should be explored. MATERIALS AND METHODS: 206 patients who
      had attended the neuro-music therapy were addressed in a structured follow-up
      questionnaire survey. 107 complete questionnaires entered analysis. Follow-up
      time was 2.65 (SD 1.1) years. RESULTS: 76% of the patients achieved a reliable
      reduction in their tinnitus scores, the overall tinnitus distress as measured by
      the Mini-TQ diminished from 11.9 (SD = 4.9) to 7.4 (SD = 5.2) points, 87% of the
      patients were satisfied by the way they were treated during therapy, and 71% of
      the patients did not undergo any further treatment after. Evaluation of
      therapeutic elements displays, that only music therapy specific interventions
      were rated helpful by the patients. Tinnitus related factors (such as tinnitus
      pitch or loudness, time since onset) did not influence therapy outcome but female
      gender, positive therapeutic relationship, and higher initial Mini-TQ scores
      became apparent as factors predicting better chances for greater therapy success.
      DISCUSSION: The "Heidelberg Model of Music Therapy for Chronic Tinnitus" seems to
      be effective in the long run. The outcome effect size of d' = 0.89, can be
      accounted for as "large" effect and falls into the upper range value compared to
      established treatments.

PMID- 22993647
TI  - HDFx: a novel biologic immunomodulator accelerates wound healing and is
      suggestive of unique regenerative powers: potential implications for the
      warfighter and disaster victims.
AB  - Recently, we reported on the discovery of a new, conserved biologic protein (35
      40 KDa), termed HDFx, that protects rats, guinea-pigs, mice, and rabbits against
      lethal hemorrhage, endotoxins, intestinal ischemic-shock, and traumatic injuries.
      It was found to stimulate several arms of the immune system. The present report
      demonstrates, for the first time, that HDFx accelerates wound healing in two
      different models (excision wound model; and incision wound model) in rats. The
      results shown, herein, indicate that HDFx produces greater rates of wound
      contraction, greater tensile strength, and more rapid healing than controls. Our
      new data also show that this biologic increases hydroxyproline content of
      granulation tissue coupled with a reduction in superoxide dismutase (SOD). In
      addition, we show that HDFx increases the levels of serum ascorbic acid and
      stimulates the mononuclear cells of the reticuloendothelial system (RES).
      Overall, these data suggest that HDFx may possess unique regenerative powers. We,
      thus, believe that HDFx can be of great potential use in diverse types of wounds
      which, otherwise, could result in difficult to treat infections and thus prevent
      sepsis and loss of body parts from amputations.

PMID- 22993648
TI  - Development of targeted therapy for a broad spectrum of cancers (pancreatic
      cancer, ovarian cancer, glioblastoma and HCC) mediated by a double promoter
      plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4
      regulatory sequences.
AB  - BACKGROUND: The human IGF2-P4 and H19 promoters are highly active in a variety of
      human cancers, while existing at a nearly undetectable level in the surrounding
      normal tissue. Single promoter vectors expressing diphtheria toxin A-fragment
      (DTA) under the control regulation of IGF2-P4 or H19 regulatory sequences (IGF2
      P4-DTA and H19-DTA) were previously successfully used in cell lines, animal
      models and recently in human patients with superficial cell carcinoma of the
      bladder, pancreatic cancer and ovarian cancer (treated with H19-DTA). However
      this targeted medicine approach may be limited, as not all cancer patients
      express high levels of H19 and it requires prerequisite diagnostic test for H19.
      Hence, a double promoter DTA-expressing vector was created, carrying on a single
      construct two separate genes expressing the diphtheria toxin A-fragment (DTA),
      from two different regulatory sequences, selected from the cancer-specific
      promoters H19 and IGF2-P4. METHODS: H19 and IGF2-P4 gene expression was tested in
      cell lines of a broad spectrum of different carcinomas (bladder, pancreas, ovary,
      glioblastoma and HCC), by RT-PCR. The therapeutic potential of the double
      promoter toxin vector H19-DTA-(IGF2)-P4-DTA was tested in the different cancer
      cell lines. RESULTS: The double promoter vector exhibited superior inhibition
      activity compared to the single promoter expression vectors, in the different
      cancer cell lines furthermore, the double promoter vector H19-DTA-P4-DTA
      exhibited augmented-than-additive anti-cancer activity relative to single
      promoter expression vectors carrying either DTA sequence alone, when tested in a
      broad spectrum of tumor cells. CONCLUSIONS: Our findings show that administration
      of H19-DTA-P4-DTA has the potential to reach tumor cells, deliver its
      intracellular toxin without targeting normal tissues, and thus may help reduce
      tumor burden, improve the quality of life of the patient; and prolong their life
      span. As H19 and IGF2 were expressed in a broad spectrum of different cancers,
      therefore we propose a double promoter expression approach for treating a variety
      of tumors expressing H19, IGF2, or both. According to this approach patients may
      be treated with a single double promoter expression toxin vector which is under
      the control of the IGF2 and H19 regulatory sequences, differentially expressed in
      those cancers. As majority of the tumor cells express H19, IGF2, or both,
      therefore the use of prerequisite diagnostic test will be unnecessary.

PMID- 22993649
TI  - Plasma glycosylphosphatidylinositol phospholipase D (GPI-PLD) and abdominal
      aortic aneurysm.
AB  - Recent reviews state that a circulating biomarker predicting aortic rupture risk
      would be a powerful tool to stratify patients with small screen-detected
      abdominal aortic aneurysm (AAA). In a current proteomic pilot-study elevated
      levels of the enzyme Glycosylphosphatidylinositol-specific phospholipase D (GPI
      PLD) was shown in patients with small AAA compared with controls without
      aneurysm. In the present study we investigated the impact of plasma GPI-PLD as a
      biomarker in patients with AAA in relation to aneurysm size, and rupture. Plasma
      GPI-PLD was measured in patients with AAA (nonruptured, n=78 and ruptured, n=55)
      and controls without aneurysm (n=41) matched by age, sex and smoking habit. The
      plasma GPI-PLD levels were significantly lower in patients with ruptured compared
      nonruptured AAA which we interpreted as a result of hemodilution due to
      hemorrhage in patients with ruptured AAA. The plasma GPI-PLD levels were similar
      in patients with nonruptured AAA compared to the controls without aneurysm.
      Furthermore, there was no correlation between plasma GPI-PLD and aneurysm size in
      the group of patients with nonruptured AAA. In conclusion, the present study
      fails to show a connection between GPI-PLD and AAA. However, the definite role of
      GPI-PLD as a predictive marker needs to be further clarified in a follow-up
      cohort study.

PMID- 22993650
TI  - BRAF mutation in papillary thyroid carcinoma.
AB  - BRAF mutation is the most common genetic alternation in thyroid cancer,
      particularly in papillary thyroid cancer (PTC). Excessive activation of BRAF/MAPK
      signaling pathway due to BRAF mutation plays a central role in the tumorigenesis
      and development of PTC. The association of BRAF mutation with poor
      clinicopathological characteristics of PTC further demonstrated the importance of
      the BRAF mutation alternation in PTC. Detection of BRAF mutation on FNA specimen
      before surgery is recommended as a useful diagnostic marker and prognostic
      indicator for PTC, and thus influences surgeon's decision on management of PTC.
      Recent studies have focused on inhibition of BRAF activation and several small
      molecules have been developed as targeting therapy.

PMID- 22993651
TI  - The clinical utility of anti-chromatin antibodies as measured by BioPlex 2200 in
      the diagnosis of systemic lupus erythematosus versus other rheumatic diseases.
AB  - BACKGROUND: The detection of autoantibodies is indispensable to systemic lupus
      erythematosus (SLE). Bioplex 2200 ANA screen is a multiplex immunoassay system
      that allows simultaneous determination of autoantibodies to extractable nuclear
      antigens (ENA) including anti-chromatin antibodies (ACAs). However, the clinical
      significance of the ACAs by this new method in SLE patients has not been studied
      in comparison with other rheumatic disorders. We performed a retrospective study
      of patients with rheumatic diseases to assess the diagnostic value of the ACAs by
      Bioplex 2200 method in SLE. METHODS: Adult patients with rheumatic complaints
      seen by rheumatologists at the Cleveland Clinic between January 2008 and February
      2010 were screened for positive anti-ENA antibodies by the Bioplex 2200. Patients
      with positive anti-ENA antibodies were classified into two populations based upon
      the presence and absence of the ACAs. We retrospectively studied the clinical and
      laboratory data of these patients. RESULTS: A total of 764 subjects with positive
      anti-ENA antibodies were screened, including 115 with positive ACAs. There were
      93 SLE patients consisting of 58 with positive ACAs and 35 with negative ACAs.
      The sensitivity, specificity, positive predictive value and negative predictive
      value of the ACAs in SLE were 62.4%, 91.5%, 50.4% and 94.6% respectively. Apart
      from SLE, positive ACAs were associated with mixed connective tissue disease
      (MCTD)/undifferentiated CTD (UCTD) and other autoimmune diseases. No correlation
      was found between the ACAs and lupus glomerulonephritis or anti-dsDNA antibodies.
      CONCLUSIONS: Measurement of the ACAs by the Bioplex 2200 is specific for
      diagnosing SLE but not useful for differentiating between SLE and MCTD/UCTD.

PMID- 22993652
TI  - Colonoscopy outcome in North of Iran (Guilan): 2006-2009.
AB  - Colonoscopy is a procedure that used largely, in assessment, screening &
      management of lower gastrointestinal disease. Some of these diseases that
      assessed are colorectal cancer, polyps & inflammatory bowel disease. The goal of
      this study is determining of frequency of lower GI disease among patient who have
      elective colonoscopy. This cross-sectional study was conducted retrospective.
      Samples collected from the census method of colonoscopy patients in Razi
      hospital, from March 21th in 2006 to March 20th in 2009. Patients' data including
      age, sex, location and type of lesion found by colonoscopy and pathology
      diagnosis were collected and at the end necessary information collected into the
      SPSS software (version 16) for analyzing with the help of statistical tests Chi
      square. Significant findings: Of 1398 patients, 683 patients (48/8 %) were male
      and 715 (51/2 %) were female 494 patients (35/3%) had normal results. Hemorrhoids
      (22/6 %) and polyps (14/8 %) were the most abundant lesions discovered by
      colonoscopy. The most common site of lesions among patients with abnormal
      colonoscopy findings, were anal canal and anus (43/8 %) and rectosigmoid (26%).
      The findings in both males and females, revealed no statistical differences.
      CONCLUSION: Colonoscopic detection of hemorrhoids is a common finding in patient
      undergone colonoscopy. The most frequent site for lesions which found in anal
      canal and anus. In addition to, normal findings had a high rate and it indicates
      that unnecessary colonoscopy have been required by physicians.

PMID- 22993653
TI  - Chewing side preference in first and all mastication cycles for hard and soft
      morsels.
AB  - Preferred chewing side is a still controversial matter and various methods used
      have yielded some inconsistencies. The aim of this study is to compare the
      preference determined in different conditions. Nineteen healthy subjects were
      offered hard (walnut) and soft (cake) foods, while the electromyography was
      recorded from their masseter muscles, in 2009 in the Research Center of Physical
      Medicine and Rehabilitation, Tabriz University of Medical Sciences, Tabriz, Iran.
      Four occurrences were determined as the side of the first chews/all chews in the
      two food types, and then analyzed for correlations and agreements. For hard food
      73.68% and for soft food 57.89% of the subjects showed preference. The comparison
      of all chews showed a highly significant preference towards the right side in
      both food types (p=0.000 & 0.003). There was both correlation and agreement
      between the first chew preferences in both food types, and an agreement between
      the first and all chew preferences in the hard food. Therefore, there seems to
      exist some laterality in mastication, which is more explicit when using hard food
      and assessing all chews.

PMID- 22993654
TI  - Estrogen receptor genes variations and breast cancer risk in Iran.
AB  - Evidence suggests that alterations in estrogen signaling pathways, including
      estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta) occur
      during breast cancer development. ER-alpha and ER-beta genes polymorphisms have
      been found to be associated with breast cancer and clinical features of the
      disease in the western countries. In the current study, we evaluated the
      hypothesis that certain sequence variants of the ER-alpha and ER-beta genes are
      associated with an additively increased risk for breast cancer in Iranian women
      breast cancer patients. The genes were scanned in 150 Iranian patients with newly
      diagnosed invasive breast tumors and in healthy control individuals by PCR single
      strand conformation polymorphism (SSCP) method. Three single nucleotide
      polymorphisms (SNPs) in codon10 (TCT->TCC), codon 352 (CCG->CCC) and codon 594
      (ACG->ACA) in ER-alpha gene and one SNP codon 392 (CTC->CTG) in ER-beta were
      revealed have additive effects in developing breast cancer and LN metastases.
      Also, SNP in codon 392 of estrogen receptor-beta gene is more effective
      (threefold) than those SNPs in codons 10, 325, 594 of estrogen receptor-alpha
      gene in developing LN metastases in breast cancer patients. SNPs in estrogen
      receptor alpha and beta have additive effects in increasing risk for developing
      breast cancer with LN metastases among Iranian women breast cancer patients.

PMID- 22993655
TI  - Successful use of topical "Ankaferd Blood Stopper" for repetitive bleedings in an
      infant with infantile hemangioma.
AB  - Infantile hemangioma (IH) is the most common vascular tumor of childhood. A major
      feature of this tumor is rapid growth during a proliferation phase in the first
      year of life, followed by contraction through a slow involution phase. Several
      complications may emerge during this course. Bleeding at the site of the lesion
      and infection are the most common complications. 'Ankaferd Blood Stopper' (ABS)
      is a hemostatic agent produced as a mixture of five separate plant extracts.
      Provision of hemostasis by ABS is independent from coagulation factors and the
      standard coagulation cascade. Furthermore, ABS has an antimicrobial effect. In
      this article, we have presented a seven-year-old infant with IH on the lower lip
      who had been admitted with the symptoms of frequent bleedings and infection, and
      who was successfully treated with topical ABS in terms of control of bleeding and
      infection. To the best of our knowledge, this is the first reported case of IH
      that has been treated with ABS for bleeding.

PMID- 22993656
TI  - Findings of multidimensional instruments for determining psychopathology in
      diabetic and non-diabetic hemodialysis patients.
AB  - OBJECTIVE: The aim of this study was to expand the research on psychiatric
      complications of end-stage renal disease (ESRD), as well as to examine the
      prevalence of a broad range of psychopathology in diabetic and non-diabetic
      hemodialysis (HD) patients. METHODS: One hundred nineteen HD patients were
      invited to enter the cross-sectional study. To assess quality of life, quality of
      sleep, mental status and depression and anxiety symptoms, the 36-item Short Form,
      Pittsburgh Sleep Quality Index (PSQI), Mini-Mental State Examination and Hospital
      Anxiety and Depression Scale, respectively, were used. RESULTS: The mean age of
      all patients was 56.9+/-16.1 years; 54 (45.4%) were female. In the diabetic
      patients group, 84.8% of the patients had low MCS scores, and 89.2% patients had
      low PCS scores; 73.9% were poor sleepers; 63.0% had cognitive decline; 62.0%
      patients were depressive symptoms; and 28.3%had symptoms of anxiety. When
      comparing the diabetic and non-diabetic patients, the diabetic patients had lower
      role-emotional, sleep duration, and sleep efficiency scores. CONCLUSIONS:
      Incorporating a standard assessment and, eventually, treatment of
      psychopathologic symptoms into the care provided to diabetic and hemodialysis
      patients might improve quality of life and sleep, depressive symptoms and, reduce
      mortality risk.

PMID- 22993657
TI  - Concurrent occurrence of primary hepatocellular and cholangiocellular carcinoma
      in the different part of the liver: a case report.
AB  - Combined hepatocellular-cholangiocarcinoma which shows features of both
      hepatocellular and biliary epithelial differentiation is a rare form of primary
      liver cancer. The rarer is that the two types of cancer occur in the different
      lobe of the same liver concurrently.

PMID- 22993658
TI  - Early-onset breast cancer in a woman with Graves' disease.
AB  - The relationship between thyroid and breast diseases has been documented, but the
      clinical significance of Graves' disease and breast cancer is unclear. We present
      a young patient with a history of Graves' disease who developed a multicentric
      infiltrating ductal carcinoma of the breast several months after discontinuing
      her treatment with propylthiouracil. Early-onset breast cancer in women without a
      family history of early breast cancer may be related to hyperthyroidism. The
      relationship between thyroid hormone and estrogen is discussed.

PMID- 22993659
TI  - Different roles of TGF-beta in the multi-lineage differentiation of stem cells.
AB  - Stem cells are a population of cells that has infinite or long-term self-renewal
      ability and can produce various kinds of descendent cells. Transforming growth
      factor beta (TGF-beta) family is a superfamily of growth factors, including TGF
      beta1, TGF-beta2 and TGF-beta3, bone morphogenetic proteins, activin/inhibin, and
      some other cytokines such as nodal, which plays very important roles in
      regulating a wide variety of biological processes, such as cell growth,
      differentiation, cell death. TGF-beta, a pleiotropic cytokine, has been proved to
      be differentially involved in the regulation of multi-lineage differentiation of
      stem cells, through the Smad pathway, non-Smad pathways including mitogen
      activated protein kinase pathways, phosphatidylinositol-3-kinase/AKT pathways and
      Rho-like GTPase signaling pathways, and their cross-talks. For instance, it is
      generally known that TGF-beta promotes the differentiation of stem cells into
      smooth muscle cells, immature cardiomyocytes, chondrocytes, neurocytes, hepatic
      stellate cells, Th17 cells, and dendritic cells. However, TGF-beta inhibits the
      differentiation of stem cells into myotubes, adipocytes, endothelial cells, and
      natural killer cells. Additionally, TGF-beta can provide competence for early
      stages of osteoblastic differentiation, but at late stages TGF-beta acts as an
      inhibitor. The three mammalian isoforms (TGF-beta1, 2 and 3) have distinct but
      overlapping effects on hematopoiesis. Understanding the mechanisms underlying the
      regulatory effect of TGF-beta in the stem cell multi-lineage differentiation is
      of importance in stem cell biology, and will facilitate both basic research and
      clinical applications of stem cells. In this article, we discuss the current
      status and progress in our understanding of different mechanisms by which TGF
      beta controls multi-lineage differentiation of stem cells.

PMID- 22993660
TI  - Cell-free derivatives from mesenchymal stem cells are effective in wound therapy.
AB  - AIM: To compare the efficacy of cell-free derivatives from Bone marrow derived
      human mesenchymal stem cells (hMSCs) in wound therapy. METHODS: hMSCs have been
      shown to play an important role in wound therapy. The present study sought to
      compare efficacy of hMSCs and cell-free derivatives of hMSCs, which may be
      clinically more relevant as they are easier to prepare, formulate and transport.
      hMSCs were isolated from human bone marrow and cultured. Multi lineage
      differentiation of hMSCs was performed to confirm their identity. The ability of
      hMSCs to migrate was evaluated using in vitro and in vivo migration assays. Cell
      lysates and conditioned medium concentrate was prepared from hMSCs (see Methods
      for details). Wounds were induced in mice and wound areas were measure before and
      after cell and cell-free derivative treatment. RNA and proteins were extracted
      from the skin and cytokine levels were measured. RESULTS: Co-culture of hMSCs
      with keratinocytes resulted in increased expression of CXCL-12 (SDF1) and ENA78
      (CXCL-5) in the conditioned media indicating that the hMSCs can respond to
      signals from keratinocytes. Accelerated wound closure was observed when hMSCs
      were injected near the site of excisional wounds in athymic as well as NOD/SCID
      mice. Interestingly, cell-free lysates prepared from hMSCs were also effective in
      inducing accelerated wound closure and increased expression of SDF1 and CXCL-5 at
      the wound bed. Additionally, concentrated media from hMSCs as well as an emulsion
      containing lysates prepared from hMSCs was also found to be more effective in
      rapid re-epithelialization than fibroblasts or vehicle-alone control. Use of cell
      free derivatives may help replace expensive wound care approaches including use
      of growth factors, epidermal/dermal substitutes, synthetic membranes, cytokines,
      and matrix components, and most importantly avoid transmission of pathogens from
      human and animal products. CONCLUSION: These results encourage development of
      derivatives of hMSCs for wound care and re-epithelialization applications.

PMID- 22993662
TI  - Isolation and characterisation of mesenchymal stem cells derived from human
      placenta tissue.
AB  - AIM: To explore the feasibility of placenta tissue as a reliable and efficient
      source for generating mesenchymal stem cells (MSC). METHODS: MSC were generated
      from human placenta tissue by enzymatic digestion and mechanical dissociation.
      The placenta MSC (PLC-MSC) were characterized for expression of cell surface
      markers, embryonic stem cell (ECS) gene expression and their differentiation
      ability into adipocytes and osteocytes. The immunosuppressive properties of PLC
      MSC on resting and phytohemagglutinin (PHA) stimulated allogenic T cells were
      assessed by means of cell proliferation via incorporation of tritium thymidine
      ((3)H-TdR). RESULTS: The generated PLC-MSC appeared as spindle-shaped cells,
      expressed common MSC surface markers and ESC transcriptional factors. They also
      differentiated into adipogenic and osteogenic lineages when induced. However,
      continuous cultivation up to passage 15 caused changes in morphological
      appearance and cellular senescence, although the stem cell nature of their
      protein expression was unchanged. In terms of their immunosuppressive properties,
      PLC-MSC were unable to stimulate resting T cell proliferation; they inhibited the
      PHA stimulated T cells in a dose dependent manner through cell to cell contact.
      In our study, MSC generated from human placenta exhibited similar mesenchymal
      cell surface markers; MSC-like gene expression pattern and MSC-like
      differentiation potential were comparable to other sources of MSC. CONCLUSION: We
      suggest that placenta tissues can serve as an alternative source of MSC for
      future experimental and clinical studies.

PMID- 22993661
TI  - Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic
      leukemia and tyrosine kinase inhibitor therapy.
AB  - Leukemia stem cells (LSCs), which constitute a minority of the tumor bulk, are
      functionally defined on the basis of their ability to transfer leukemia into an
      immunodeficient recipient animal. The presence of LSCs has been demonstrated in
      acute lymphoblastic leukemia (ALL), of which ALL with Philadelphia chromosome
      positive (Ph(+)). The use of imatinib, a tyrosine kinase inhibitor (TKI), as part
      of front-line treatment and in combination with cytotoxic agents, has greatly
      improved the proportions of complete response and molecular remission and the
      overall outcome in adults with newly diagnosed Ph(+) ALL. New challenges have
      emerged with respect to induction of resistance to imatinib via Abelson tyrosine
      kinase mutations. An important recent addition to the arsenal against Ph(+)
      leukemias in general was the development of novel TKIs, such as nilotinib and
      dasatinib. However, in vitro experiments have suggested that TKIs have an
      antiproliferative but not an antiapoptotic or cytotoxic effect on the most
      primitive ALL stem cells. None of the TKIs in clinical use target the LSC. Second
      generation TKI dasatinib has been shown to have a more profound effect on the
      stem cell compartment but the drug was still unable to kill the most primitive
      LSCs. Allogeneic stem cell transplantation (SCT) remains the only curative
      treatment available for these patients. Several mechanisms were proposed to
      explain the resistance of LSCs to TKIs in addition to mutations. Hence, TKIs may
      be used as a bridge to SCT rather than monotherapy or combination with standard
      chemotherapy. Better understanding the biology of Ph(+) ALL will open new avenues
      for effective management. In this review, we highlight recent findings relating
      to the question of LSCs in Ph(+) ALL.

PMID- 22993663
TI  - MicroRNAs, stem cells and cancer stem cells.
AB  - This review discusses the various regulatory characteristics of microRNAs that
      are capable of generating widespread changes in gene expression via post
      translational repression of many mRNA targets and control self-renewal,
      differentiation and division of cells. It controls the stem cell functions by
      controlling a wide range of pathological and physiological processes, including
      development, differentiation, cellular proliferation, programmed cell death,
      oncogenesis and metastasis. Through either mRNA cleavage or translational
      repression, miRNAs alter the expression of their cognate target genes; thereby
      modulating cellular pathways that affect the normal functions of stem cells,
      turning them into cancer stem cells, a likely cause of relapse in cancer
      patients. This present review further emphasizes the recent discoveries on the
      functional analysis of miRNAs in cancer metastasis and implications on miRNA
      based therapy using miRNA replacement or anti-miRNA technologies in specific
      cancer stem cells that are required to establish their efficacy in controlling
      tumorigenic potential and safe therapeutics.

PMID- 22993664
TI  - Generation of a human embryonic stem cell line stably expressing high levels of
      the fluorescent protein mCherry.
AB  - AIM: The generation and characterization of a human embryonic stem cell (hESC)
      line stably expressing red fluorescent mCherry protein. METHODS: Lentiviral
      transduction of a ubiquitously-expressed human EF-1alpha promoter driven mCherry
      transgene was performed in MEL2 hESC. Red fluore-scence was assessed by
      immunofluorescence and flow cytometry. Pluripotency of stably transduced hESC was
      determined by immunofluorescent pluripotency marker expression, flow cytometry,
      teratoma assays and embryoid body-based differentiation followed by reverse
      transcriptase-polymerase chain reaction. Quantification of cell motility and
      survival was performed with time lapse microscopy. RESULTS: Constitutively
      fluorescently-labeled hESCs are useful tools for facile in vitro and in vivo
      tracking of survival, motility and cell spreading on various surfaces before and
      after differentiation. Here we describe the generation and characterization of a
      hESC line (MEL2) stably expressing red fluorescent protein, mCherry. This line
      was generated by random integration of a fluorescent protein-expressing cassette,
      driven by the ubiquitously-expressed human EF-1alpha promoter. Stably transfected
      MEL2-mCherry hESC were shown to express pluripotency markers in the nucleus
      (POU5F1/OCT4, NANOG and SOX2) and on the cell surface (SSEA4, TRA1-60 and
      TG30/CD9) and were shown to maintain a normal karyotype in long-term (for at
      least 35 passages) culture. MEL2-mCherry hESC further readily differentiated into
      representative cell types of the three germ layers in embryoid body and teratoma
      based assays and, importantly, maintained robust mCherry expression throughout
      differentiation. The cell line was next adapted to single-cell passaging,
      rendering it compatible with numerous bioengineering applications such as
      measurement of cell motility and cell spreading on various protein modified
      surfaces, quantification of cell attachment to nanoparticles and rapid estimation
      of cell survival. CONCLUSION: The MEL2-mCherry hESC line conforms to the criteria
      of bona fide pluripotent stem cells and maintains red fluorescence throughout
      differentiation, making it a useful tool for bioengineering and in vivo tracking
      experiments.

PMID- 22993665
TI  - Treatment strategy for colorectal cancer with resectable synchronous liver
      metastases: Is any evidence-based strategy possible?
AB  - Fifteen percent to twenty-five percent of patients affected by colorectal cancer
      presents with liver metastases at diagnosis. In resectable cases, surgery is the
      only potentially curative treatment and achieves survival rates up to 50% at 5
      years. Management is complex, as colorectal resection, liver resection,
      chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have
      to be integrated. Modern medical practice usually relies on evidence-based
      protocols. Levels of evidence for synchronous metastases are poor: published
      studies include few recent prospective series and several retrospective analyses
      collecting a limited number of patients across long periods of time. Data are
      difficult to be generalized and are mainly representative of single centre's
      experience, biased by local recruitment, indications and surgical technique. In
      this context, surgeons have to renounce to "evidence-based medicine" and to adopt
      a sort of "experience-based medicine". Anyway, some suggestions are possible.
      Simultaneous colorectal and liver resection can be safely performed whenever
      minor hepatectomies are planned, while a case-by-case evaluation is mandatory in
      case of more complex procedures. Neoadjuvant chemotherapy is preferentially
      scheduled for patients with advanced metastatic tumors to assess disease biology
      and to control lesions. It can be safely performed with primary tumor in situ,
      even planning simultaneous resection at its end. Locally advanced mid/low rectal
      tumor represents a further indication to neoadjuvant therapies, even if
      treatment's schedule is not yet standardized. In summary, several issues have to
      be solved, but every single HPB centre should define its proper strategy to
      optimize patient's selection, disease control and safety and completeness of
      surgery.

PMID- 22993666
TI  - Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant
      protein-1 as markers of fibrosis in hepatitis C virus Egyptians.
AB  - AIM: To assess vitamin D in hepatitis C patients and its relationship to
      interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1).
      METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype
      number IV-infected patients and 25 age- and gender-matched healthy subjects.
      Venous blood samples were obtained. Samples were allowed to clot and sera were
      separated by centrifugation and stored at -20  degrees C. A 25 hydroxy vitamin D
      assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was
      carried out using a commercial kit purchased from Incstar Corporation. IL-17 and 
      23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative
      polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV
      genotype IV-infected subjects were included in the study. The mean +/- SD were
      determined, a t-test for comparison of means of different parameters was used.
      Correlation analysis was done using Pearson's correlation. Differences among
      different groups were determined using the Kruskal-Wallis test. RESULTS: The mean
      vitamin D level in HCV patients (group I) was 15 +/- 5.2 ng/mL while in control
      (group II) was 39.7 +/- 10.8. For active vitamin D in group I as 16.6 +/- 4.8
      ng/mL while in group II was 41.9 +/- 7.9. IL-23 was 154 +/- 97.8 in group I and
      6.7 +/- 2.17 in group II. IL-17 was 70.7 +/- 72.5 in cases and 1.2 +/- 0.4 in
      control. MCP-1 was 1582 +/- 794.4 in group I and 216.1 +/- 5.38 in group II.
      Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control
      group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of
      the control group. One hundred percent of the cirrhotic patients and 40% of non
      cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1
      were markedly increased in HCV-infected patients in comparison to controls.A
      significant negative correlation between vitamin D and IL-17 and -23 and MCP-1
      was detected. HCV-infected males and females showed no differences with respect
      to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was
      negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P =
      0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1.
      We classified the patients according to sonar findings into four groups. Group Ia
      with bright hepatomegaly and included 14 patients. Group Ib with perihepatic
      fibrosis and included 11 patients. Group Ic with liver cirrhosis and included 11
      patients. Group Id with hepatocellular carcinoma (HCC) and included 14 patients.
      Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and
      much lower in patients with HCC, and this difference was highly significant (P =
      0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the
      differences were highly significant (P = 0.0001). CONCLUSION: Whether the
      deficiency of vitamin D is related to HCV-induced chronic liver disease or
      predisposing factor for higher viral load is a matter of debate.

PMID- 22993667
TI  - A rare cause of drug-induced hepatitis in an immunocompromised patient and the
      role of glutathione.
AB  - The Food and Drug Administration (FDA) has issued a warning on numerous herbal
      drugs, including many popular products at General Nutrition Centers (GNC),
      regarding unstudied hepatotoxicity. There have been recent reports of GNC
      products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal
      medications are over-the-counter products and are not investigated thoroughly by
      the FDA. Given that the most common outpatient laboratory abnormality is elevated
      liver transaminases, a sign of hepatocellular toxicity; it is not surprising that
      some of these products end up causing hepatic dysfunction, especially when taken
      in large volume. There are numerous herbal supplements that are hepatotoxic,
      however, these medications have a much more significant effect in human
      immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which
      is secondary to depleted glutathione. We present a rare case of drug induced
      hepatitis secondary to herbal medications used to treat HIV and elucidate the
      role of glutathione depletion in immunocompromised patients.

PMID- 22993668
TI  - A middle-aged lady with a pyogenic liver abscess caused by Clostridium
      perfringens.
AB  - The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is
      a rare, but rapidly fatal infection. It is usually associated with malignancy and
      immunosuppression. We report the case of 50-year-old lady with the secondary
      liver metastases from rectal cancer presented with fever and epigastric pain. The
      identification of Gram-positive bacilli septicaemia, the presence of gas-forming
      liver abscess and massive intravascular hemolysis should lead to the suspicion of
      C. perfringens infection. Here we review twenty cases published since 1990 and
      their clinical features are discussed. The importance of "an aggressive treatment
      policy" with multidisciplinary team approach is emphasized.

PMID- 22993669
TI  - Chemical Diversity of Metabolites from Fungi, Cyanobacteria, and Plants Relative
      to FDA-Approved Anticancer Agents.
AB  - A collaborative project has been undertaken to explore filamentous fungi,
      cyanobacteria, and tropical plants for anti-cancer drug leads. Through principal
      component analysis, the chemical space covered by compounds isolated and
      characterized from these three sources over the last four years was compared to
      each other and to the chemical space of selected FDA-approved anticancer drugs.
      Using literature precedence, nine molecular descriptors were examined: molecular
      weight, number of chiral centers, number of rotatable bonds, number of acceptor
      atoms for H-bonds (N,O,F), number of donor atoms for H-bonds (N and O),
      topological polar surface area using N,O polar contributions, Moriguchi octanol
      water partition coefficient, number of nitrogen atoms, and number of oxygen
      atoms. Four principal components explained 87% of the variation found among 343
      bioactive natural products and 96 FDA-approved anticancer drugs. Across the four
      dimensions, fungal, cyanobacterial and plant isolates occupied both similar and
      distinct areas of chemical space that collectively aligned well with FDA-approved
      anticancer agents. Thus, examining three separate re-sources for anticancer drug
      leads yields compounds that probe chemical space in a complementary fashion.

PMID- 22993670
TI  - Histomorphometric analysis of the spine and femur in ovariectomized rats using
      micro-computed tomographic scan.
AB  - OBJECTIVE: The purpose of this study was to evaluate the different patterns of
      bone loss between the lumbar spine and the femur after ovariectomy in rats.
      METHODS: Twenty-four female Sprague-Dawley rats underwent a sham operation (the
      sham group) or bilateral ovariectomy (the ovariectomized group). Four and eight
      weeks after operation, six rats from each of the two groups were euthanized.
      Serum biochemical markers of bone turnover including osteocalcin and alkaline
      phosphatase (ALP), which are sensitive biochemical markers of bone formation, and
      the telopeptide fragment of type I collagen C-terminus (CTX), which is a
      sensitive biochemical marker of bone resorption, were analyzed. Bone
      histomorphometric parameters of the 4th lumbar vertebrae and femur were
      determined by micro-computed tomography. RESULTS: Ovariectomized rats were found
      to have higher osteocalcin, ALP and CTX levels than sham controls. Additionally,
      8 weeks after ovariectomy in the OVX group, serum levels of osteocalcin, ALP and
      CTX were significantly higher than those of 4 weeks after ovariectomy. Bone loss
      after ovariectomy was more extensive in the 4th lumbar spine compared to the
      femur. Bone loss in the 4th lumbar spine was mainly caused by trabecular
      thinning, but in the femur, it was mainly caused by trabecular elimination.
      CONCLUSION: The present study demonstrates different patterns of bone loss
      between the 4th lumbar spine and the femur in ovariectomized rats. Therefore,
      when considering animal models of osteoporosis, it is important that bone sites
      should be taken into account.

PMID- 22993671
TI  - Association study of fibroblast growth factor 2 and fibroblast growth factor
      receptors gene polymorphism in korean ossification of the posterior longitudinal
      ligament patients.
AB  - OBJECTIVE: The aim of this study was to determine whether single nucleotide
      polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast
      growth factor receptor (FGFR) genes are associated with ossification of the
      posterior longitudinal ligament (OPLL). METHODS: A total of 157 patients with
      OPLL and 222 controls were recruited for a case control association study
      investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To
      identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and
      OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395,
      rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793,
      rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed
      using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. RESULTS: Of
      the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the
      susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence
      interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence
      interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition
      showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in
      the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and
      rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament
      flavum (OLF). CONCLUSION: The results of the present study revealed that an FGFR1
      SNP was significantly associated with OPLL and that a SNP in FGF2 was associated
      with conditions that were comorbid with OPLL (DISH and OLF).

PMID- 22993672
TI  - Intracranial Meningiomas, WHO Grade Il : Prognostic Implications of
      Clinicopathologic Features.
AB  - OBJECTIVE: Intracranial meningiomas are primarily benign tumors with a good
      prognosis. Although WHO grade II meningiomas are rare (2-10%), WHO grade II
      meningiomas have higher recurrence and mortality rates than benign. We evaluated
      the patient recurrence rate and investigated the prognostic factors of WHO grade
      II meningiomas. METHODS: Between 1993 and 2005, 55 patients were diagnosed with
      WHO grade II meningiomas in our hospital. WHO grade II meningiomas (n=55) were
      compared with other WHO grades meningiomas (I, n=373; and III, n=20). The
      patients had a median age of 48.4 years (range, 14-17 years), a male-to-female
      ratio of 26 : 29, and a mean follow-up time of 45 months (range, 3-175 months).
      RESULTS: In WHO grade II meningiomas, only the extent of resection was a
      significant prognostic factor. Post-operative radiotherapy had no significant
      influence on tumor recurrence (p=0.053). The relative risk of recurrence was
      significantly higher in WHO grade II meningiomas with incomplete resection
      (10/27, RR=37%) than in WHO grade II meningiomas with complete resection (4/28,
      RR=14%) regardless of post-operative radiotherapy. In the incomplete resection
      group, Simpson grade III or IV had a significantly high risk of recurrence
      regardless of post-operative RT (n=3, RR=100%) However, if the degree of
      resection was Simpson grade II, the recurrence rate was similar to the complete
      resection group even though post-operative RT was not performed. CONCLUSION:
      Complete resection was the most powerful independent predictive factor of the
      recurrence rate in WHO grade II meningiomas. Post-operative adjuvant RT was not a
      significant factor in this study.

PMID- 22993673
TI  - Posterior cervical fixation with a nitinol shape memory loop for primary surgical
      stabilization of atlantoaxial instability: a preliminary report.
AB  - OBJECTIVE: To evaluate a new posterior atlantoaxial fixation technique using a
      nitinol shape memory loop as a simple method that avoids the risk of vertebral
      artery or nerve injury. METHODS: We retrospectively evaluated 14 patients with
      atlantoaxial instability who had undergone posterior C1-2 fusion using a nitinol
      shape memory loop. The success of fusion was determined clinically and
      radiologically. We reviewed patients' neurologic outcomes, neck disability index
      (NDI), solid bone fusion on cervical spine films, changes in posterior
      atlantodental interval (PADI), and surgical complications. RESULTS: Solid bone
      fusion was documented radiologically in all cases, and PADI increased after
      surgery (p<0.05). All patients remained neurologically intact and showed
      improvement in NDI score (p<0.05). There were no surgical complications such as
      neural tissue or vertebral artery injury or instrument failure in the follow-up
      period. CONCLUSION: Posterior C1-2 fixation with a nitinol shape memory loop is a
      simple, less technically demanding method compared to the conventional technique
      and may avoid the instrument-related complications of posterior C1-2 screw and
      rod fixation. We introduce this technique as one of the treatment options for
      atlantoaxial instability.

PMID- 22993674
TI  - Midline-Splitting Open Door Laminoplasty Using Hydroxyapatite Spacers :
      Comparison between Two Different Shaped Spacers.
AB  - OBJECTIVE: Although hydroxyapatite (HA) spacer has been used for laminoplasty,
      there have been no reports on factors associated with fusion and on the effects
      of HA shape. METHODS: During January 2004 and January 2010, 45 patients with
      compressive cervical myelopathy underwent midline-splitting open door
      laminoplasty with winged (33 cases) and wingless (12 cases) HAs by a single
      surgeon. Minimal and mean follow up times were 12 and 28.1 months, respectively.
      Japanese Orthopedic Association (JOA) score was used for clinical outcome
      measurement. Cervical X-rays were taken preoperatively, immediately post
      operatively, and after 3, 6, and 12 months and computed tomography scans were
      performed preoperatively, immediately post-operatively and after 12 months.
      Cervical lordosis, canal dimension, fusion between lamina and HA, and affecting
      factors of fusion were analyzed. RESULTS: All surgeries were performed on 142
      levels, 99 in the winged and 43 in the wingless HA groups. JOA scores of the
      winged group changed from 10.4+/-2.94 to 13.3+/-2.35 and scores of the wingless
      group changed from 10.8+/-2.87 to 13.8+/-3.05. There was no significant
      difference on lordotic and canal dimensional change between two groups. Post
      operative 12 month fusion rate between lamina and HA was significantly lower in
      the winged group (18.2 vs. 48.8% p=0.001). Multivariate analysis showed that
      ossification of the posterior longitudinal ligament, male gender, and wingless
      type HA were significantly associated with fusion. CONCLUSION: Clinical outcome
      was similar in patients receiving winged and wingless HA, but the wingless type
      was associated with a higher rate of fusion between HA and lamina at 12 months
      post-operatively.

PMID- 22993675
TI  - Electrophysiological and behavioral changes by phosphodiesterase 4 inhibitor in a
      rat model of alcoholic neuropathy.
AB  - OBJECTIVE: Alcoholic neuropathy is characterized by allodynia (a discomfort
      evoked by normally innocuous stimuli), hyperalgesia (an exaggerated pain in
      response to painful stimuli) and spontaneous burning pain. The aim of the present
      study is to investigate the effect of rolipram, a phosphodiesterase 4 inhibitor,
      against alcohol-induced neuropathy in rats. METHODS: Allodynia was induced by
      administering 35% v/v ethanol (10 g/kg; oral gavage) to Spraue-Dawley rats for 8
      weeks. Rolipram and saline (vehicle) were administered intraperitoneally.
      Mechanical allodynia was measured by using von Frey filaments. Somatosensory
      evoked potential (SEP) was proposed as complementary measure to assess the
      integrity of nerve pathway. RESULTS: The ethanol-induced mechanical allodynia
      began to manifest from 3 week, and then peaked within 1 week. Beginning from 3
      week, latency significantly started to increased in control group. In rolipram
      treated rats, the shorter latency was sustained until 8 weeks (p<0.05). The
      mechanical allodynia, which began to manifest on the 3 weeks, intraperitoneal
      injections of rolipram sustained statistical difference until 8 weeks, the final
      week of the study (p<0.05). CONCLUSION: This study suggests that rolipram might
      alleviate mechanical allodynia induced by alcohol in rats, which clearly has
      clinical implication.

PMID- 22993676
TI  - Treatment outcomes of pediatric craniopharyngioma : a 15-year retrospective
      review of 35 cases.
AB  - OBJECTIVE: The aim of this study was to describe a single center's experience in
      the management of craniopharyngiomas in children over a 15-year period. METHODS:
      The clinical records of pediatric patients treated for craniopharyngiomas between
      December 1995 and February 2011 were reviewed. Thirty-five pediatric patients
      diagnosed with craniopharyngioma were treated, and their medical records and
      imaging data were analyzed retrospectively. RESULTS: The mean follow-up duration
      was 76 months (range, 10-195). Overall survival and local control rates at 10
      years were 94.7+/-5.1% and 37.1+/-11.9%, respectively. The female-to-male ratio
      was 16 : 19, and the mean age was 8.6 years (range, 1-17). Initially, gross total
      resection (GTR) was performed in 30 patients; subtotal resection (STR) followed
      by radiotherapy was performed in 5 patients. Of the 14 cases that showed
      recurrence after GTR, 5 patients were treated with GTR, 1 with radiation therapy
      (RT), 4 with gamma knife radiosurgery (GKRS), and 4 with subtotal resection
      followed by RT. No patients who underwent RT or GKRS had recurrences. Two cases
      with recurrence after STR followed by RT were treated with GTR. One patient died
      of hormonal insufficiency 64 months after the first surgery. The overall median
      time progression was 51.2 months (range, 3-182) : 49.7 months in the patients who
      underwent GTR and 60.2 months in the patients who underwent STR followed by RT.
      CONCLUSION: If safe resection is possible, GTR at the initial treatment should be
      attempted to reduce the tumor recurrence. However, if the tumor recurs after the
      first surgery, RT or GKRS with/without reoperation may be an effective salvage
      treatment for recurrent craniopharyngioma.

PMID- 22993677
TI  - Microvascular decompression for primary trigeminal neuralgia : short-term follow
      up results and prognostic factors.
AB  - OBJECTIVE: The aim of this prospective study was to demonstrate the influence of
      some factors on the prognosis of microvascular decompression in 37 patients with
      trigeminal neuralgia. METHODS: The results of microvascular decompression (MVD)
      in 37 patients with trigeminal neuralgia were evaluated at 6 months after surgery
      and were compared with clinical and operative findings. RESULTS: The sex of the
      patient, the patient's age at surgery, the side of the pain, and the duration of
      symptoms before surgery did not play any significant roles in prognosis. Also,
      the visual analogue scale (VAS) of the patient, the duration of each pain attack,
      and the frequency of pain over 24 hours did not play any significant roles in
      prognosis. In addition, intraoperative detection of the type of conflicting
      vessel, the degree of severity of conflict, and the location of the conflict
      around the circumference of the root did not play any roles in prognosis. The
      only factors affecting the prognosis in MVD surgery were intraoperative detection
      of the site of the conflict along the root and neuroradiological compression
      signs on preoperative magnetic resonance imaging (MRI)/magnetic resonance
      angiography (MRA). CONCLUSION: These findings demonstrated that if neurovascular
      compression is seen on preoperative MRI/MRA and/or compression is found
      intraoperative at the root entry zone, then the patient will most likely benefit
      from MVD surgery.

PMID- 22993678
TI  - Destructive radiologic development of intravascular papillary endothelial
      hyperplasia on skull bone.
AB  - Intravascular papillary endothelial hyperplasia (IPEH) is a rare vascular benign
      lesion that rarely involves the central nervous system with or without skull
      invasion. We report a rare case of IPEH on the skull bone, which displayed
      destructive radiologic development associated with hemorrhage. A 14-year-old male
      presented with an incidentally detected a small enhancing, left frontal
      osteolytic lesion. Previously, he underwent operation and received adjuvant
      chemoradiation therapy for cerebellar medulloblastoma. Follow-up magnetic
      resonance imaging revealed a left frontal bone lesion, which expanded to an
      approximately 2 cm-sized well-circumscribed osteolytic lesion associated with
      hemorrhage for 20 months. Frontal craniectomy and cranioplasty were performed.
      Destructive change was detected on the inner table and diploic space of the
      skull. The mass had a cystic feature with hemorrhagic content without dural
      attachment. Pathologic examination showed the capsule consisted of parallel
      collagen lamellae representing a vascular wall, vascular lumen, which was
      pathognomonic for IPEH. Immunohistochemical staining revealed that the capsule
      was positive for CD34 and factor VIII, which favor the final diagnosis of IPEH.
      This was the first case of intracalvarial IPEH.

PMID- 22993679
TI  - Intravascular Papillary Endothelial Hyperplasia (Masson tumor) of the Skull :
      Case Report and Literature Review.
AB  - A 10-year-old female patient presented with a rapidly growing nodular mass lesion
      on her right frontal area. On skull radiography and computed tomography (CT)
      imaging, this mass had a well-demarcated punch-out lesion with a transdiploic,
      exophytic soft tissue mass nodule on the frontal scalp. Magnetic resonance (MR)
      imaging revealed the presence of a 1.5*1.2*1 cm sized calvarial lesion. This
      lesion was hypointense on T1 and heterogenous hyperintense on T2 weighted MR
      images, and exhibited heterogeneous enhancement of the soft tissue filling the
      punch-out lesion after intravenous administration of gadolinium. En block removal
      of the tumor with resection of the rim of the normal bone was performed. The
      pathological diagnosis was intravascular papillary endothelial hyperplasia
      (IPEH). After surgery, no recurrence was found for 8 months. IPEH is a rare and
      benign reactive lesion usually found in thrombosed subcutaneous blood vessels.
      Involvement of skull bone is rare. In this article, we present a case of IPEH
      involving the calvarium, in a 10-year-old woman.

PMID- 22993680
TI  - Alveolar soft part sarcoma metastasized to both the skull and the brain.
AB  - Alveolar soft part sarcoma (ASPS) with skull and brain metastases is extremely
      rare. A 53-year-old patient diagnosed as skull metastasis of ASPS visited our
      clinic complaining of an outgrowing scalp mass in spite of radiation therapy.
      Past medical history revealed that the patient had been diagnosed and treated for
      ASPS of the thigh 4 years ago. Magnetic resonance imaging revealed a hyperintense
      ovoid mass on the T2-weighted image, an isointense on the T1-weighted image, and
      a homogeneous enhanced mass with gadolinium. Another small-sized enhanced mass
      with mild peritumoral swelling was found at the deep white matter of the left
      frontal lobe. A gross total resection of the skull lesion with cranioplasty was
      performed for the surgical defect. A histologic examination of the specimens
      revealed metastatic ASPS involving the skull. Surgery with a total removal of the
      lesions may be effective for improving a patient's symptoms especially from
      neurological dysfunction.

PMID- 22993681
TI  - Syringo-subarachnoid-peritoneal shunt using T-tube for treatment of post
      traumatic syringomyelia.
AB  - Various surgical procedures for the treatment of post-traumatic syringomyelia
      have been introduced recently, but most surgical strategies have been unreliable.
      We introduce the concept and technique of a new shunting procedure, syringo
      subarachnoid-peritoneal shunt. A 54-year-old patient presented to our hospital
      with a progressive impairment of motion and position sense on the right side.
      Sixteen years before this admission, he had been treated by decompressive
      laminectomy for a burst fracture of L1. On his recent admission, magnetic
      resonance (MR) imaging studies of the whole spine revealed the presence of a huge
      syrinx extending from the medulla to the L1 vertebral level. We performed a
      syringo-subarachnoid-peritoneal shunt, including insertion of a T-tube into the
      syrinx, subarachnoid space and peritoneal cavity. Clinical manifestations and
      radiological findings improved after the operation. The syringo-subarachnoid
      peritoneal shunt has several advantages. First, fluid can communicate freely
      between the syrinx, the subarachnoid space, and the peritoneal cavity. Secondly,
      we can prevent shunt catheter from migrating because dural anchoring of the T
      tube is easy. Finally, we can perform shunt revision easily, because only one arm
      of the T-tube is inserted into the intraspinal syringx cavity. We think that this
      procedure is the most beneficial method among the various shunting procedures.

PMID- 22993682
TI  - Clinical and radiological findings of nerve root herniation after discectomy of
      lumbar disc herniation.
AB  - The authors report 2 cases of nerve root herniation after discectomy of a large
      lumbar disc herniation caused by an unrecognized dural tear. Patients complained
      of the abrupt onset of radiating pain after lumbar discectomy. Magnetic resonance
      imaging showed cerebrospinal fluid signal in the disc space and nerve root
      displacement into the disc space. Symptoms improved after the herniated nerve
      root was repositioned. Clinical symptoms and suggestive radiologic image findings
      are important for early diagnosis and treatment.

PMID- 22993683
TI  - Spinal intramedullary ependymal cysts : a case report and review of the
      literature.
AB  - We report a rare case of a spinal intramedullary ependymal cyst in a 46-year-old
      female and review the 17 pathologically proven cases in the literature. The
      patient presented with a two-week history of gradually increasing tingling in her
      left posterior thigh and calf. A preoperative magnetic resonance image revealed a
      well-defined intramedullary cystic lesion on the ventral side of the spinal cord
      at the T11 to T12 levels. The lesion was hyper intense in T2-weighted images and
      hypointense in T1-weighted. The patient underwent a right-side hemilaminectomy at
      the T11 to T12 levels and fenestration of the cyst wall. After having the cyst
      wall partially removed and communication established between the cyst and the
      subarachnoid space, the patient improved neurologically. A histological study of
      the surgical specimens revealed that the cyst wall consisted of glial cells lined
      by a simple cuboidal to columnar epithelium. An immunohistochemical examination
      of the cells lining the cyst wall was positive for S-100 protein, glial
      fibrillary acidic protein, epithelial membrane antigen, and cytokeratin. We
      suggest that the optimal treatment of intramedullary ependymal cysts creates
      adequate communication between the cyst and the subarachnoid space.

PMID- 22993684
TI  - Hybridization of common reed in North America? The answer is blowing in the wind.
AB  - BACKGROUND AND AIMS: We review evidence for hybridization of Phragmites australis
      in North America and the implications for the persistence of native P. australis
      ssp. americanus populations in North America. We also highlight the need for an
      updated classification system, which takes P. australis intraspecific variation
      and hybridization into account. METHODOLOGY: We reviewed available published, in
      press and in preparation literature to assess the likelihood of hybridization and
      interbreeding in genotypes of P. australis present in North America. PRINCIPAL
      RESULTS: Experimental results demonstrate that hybridization among introduced and
      native haplotypes is possible within the genus Phragmites, yet evidence that
      hybridization has occurred naturally is only starting to emerge. The lag in
      identifying hybridization in Phragmites in North America may be related to under
      sampling in some parts of North America and to a lack of molecular tools that
      provide the capability to recognize hybrids. CONCLUSIONS: Our understanding of
      the gene flow within and between species in the genus Phragmites is moving at a
      fast pace, especially on the east and Gulf coasts of North America. More
      attention should also be focused on the Great Lakes region, the southwestern and
      the west coast of the USA, where sympatry has created opportunities for
      hybridization. Where hybridizations have been detected, there are currently no
      published data on how hybridization affects plant vigour, morphology,
      invasiveness or conservation of the genetic integrity of the North American
      native subspecies. We conclude that the detection of more hybridization is highly
      likely and that there is a need to develop new markers for the different
      Phragmites species and lineages to fill current knowledge gaps. Finally, we
      suggest that the classification system for P. australis should be updated and
      published to help clarify the nomenclature.

PMID- 22993685
TI  - How to suppress undesired synchronization.
AB  - Examples of synchronization can be found in a wide range of phenomena such as
      neurons firing, lasers cascades, chemical reactions, and opinion formation.
      However, in many situations the formation of a coherent state is not pleasant and
      should be mitigated. For example, the onset of synchronization can be the root of
      epileptic seizures, traffic congestion in networks, and the collapse of
      constructions. Here we propose the use of contrarians to suppress undesired
      synchronization. We perform a comparative study of different strategies, either
      requiring local or total knowledge, and show that the most efficient one solely
      requires local information. Our results also reveal that, even when the
      distribution of neighboring interactions is narrow, significant improvement is
      observed when contrarians sit at the highly connected elements. The same
      qualitative results are obtained for artificially generated networks and two real
      ones, namely, the Routers of the Internet and a neuronal network.

PMID- 22993686
TI  - Femtosecond-pulsed plasmonic nanotweezers.
AB  - We demonstrate for the first time plasmonic nanotweezers based on Au bowtie
      nanoantenna arrays (BNAs) that utilize a femtosecond-pulsed input source to
      enhance trapping of both Rayleigh and Mie particles. Using ultra-low input power
      densities, we demonstrate that the high-peak powers associated with a femtosecond
      source augment the trap stiffness to 2x that of nanotweezers employing a
      continuous-wave source, and 5x that of conventional tweezers using a femtosecond
      source. We show that for trapped fluorescent microparticles the two-photon
      response is enhanced by 2x in comparison to the response without nanoantennas. We
      also demonstrate tweezing of 80-nm diameter Ag nanoparticles, and observe an
      enhancement of the second-harmonic signal of ~3.5x for the combined nanoparticle
      BNA system compared to the bare BNAs. Finally, under select illumination
      conditions, fusing of Ag nanoparticles to the BNAs is observed which holds
      potential for in situ fabrication of three-dimensional, bimetallic nanoantennas.

PMID- 22993687
TI  - A Polycomb complex remains bound through DNA replication in the absence of other
      eukaryotic proteins.
AB  - Propagation of chromatin states through DNA replication is central to epigenetic
      regulation and can involve recruitment of chromatin proteins to replicating
      chromatin through interactions with replication fork components. Here we show
      using a fully reconstituted T7 bacteriophage system that eukaryotic proteins are
      not required to tether the Polycomb complex PRC1 to templates during DNA
      replication. Instead, DNA binding by PRC1 can withstand passage of a simple
      replication fork.

PMID- 22993688
TI  - Production of graphite chloride and bromide using microwave sparks.
AB  - Chemically modified graphite is an economical material with promising
      applications in its own right or as an intermediate in the synthesis of graphene.
      However, because of its extreme chemical inertness, to date only two methods
      oxidation and fluorination-have been found which can modify graphite with high
      yield and large throughput. Herein, we describe a third chemical approach for the
      synthesis of large quantities of highly modified graphite which uses a microwave
      sparks-assisted halogenation reaction. The resulting graphite halide can easily
      be exfoliated into monolayer graphene in organic solvents. The structure and
      electronic properties of the original graphene can be recovered after thermal
      annealing of the graphene halide. Furthermore, the graphene halide can be further
      modified by a variety of organic functional groups. Solution-processed field
      effect transistors based on the graphene halides resulted in device performances
      were comparable to, or even better than, that of graphene oxide.

PMID- 22993689
TI  - Archaeal proteins Nop10 and Gar1 increase the catalytic activity of Cbf5 in
      pseudouridylating tRNA.
AB  - Cbf5 is a pseudouridine synthase that usually acts in a guide RNA-dependent
      manner as part of H/ACA small ribonucleoproteins; however archaeal Cbf5 can also
      act independently of guide RNA in modifying uridine 55 in tRNA. This guide
      independent activity of Cbf5 is enhanced by proteins Nop10 and Gar1 which are
      also found in H/ACA small ribonucleoproteins. Here, we analyzed the specific
      contribution of Nop10 and Gar1 for Cbf5-catalyzed pseudouridylation of tRNA.
      Interestingly, both Nop10 and Gar1 not only increase Cbf5's affinity for tRNA,
      but they also directly enhance Cbf5's catalytic activity by increasing the k(cat)
      of the reaction. In contrast to the guide RNA-dependent reaction, Gar1 is not
      involved in product release after tRNA modification. These results in conjunction
      with structural information suggest that Nop10 and Gar1 stabilize Cbf5 in its
      active conformation; we hypothesize that this might also be true for guide-RNA
      dependent pseudouridine formation by Cbf5.

PMID- 22993690
TI  - Integrating multi-origin expression data improves the resolution of deep
      phylogeny of ray-finned fish (Actinopterygii).
AB  - The actinopterygians comprise nearly one-half of all extant vertebrate species
      and are very important for human well-being. However, the phylogenetic
      relationships among certain groups within the actinopterygians are still
      uncertain, and debates about these relationships have continued for a long time.
      Along with the progress achieved in sequencing technologies, phylogenetic
      analyses based on multi-gene sequences, termed phylogenomic approaches, are
      becoming increasingly common and often result in well-resolved and highly
      supported phylogenetic hypotheses. Based on the transcriptome sequences generated
      in this study and the extensive expression data currently available from public
      databases, we obtained alignments of 274 orthologue groups for 26 scientifically
      and commercially important actinopterygians, representing 17 out of 44 orders
      within the class Actinopterygii. Using these alignments and probabilistic
      methods, we recovered relationships between basal actinopterygians and teleosts,
      among teleosts within protacanthopterygians and related lineages, and also within
      acanthomorphs. These relationships were recovered with high confidence.

PMID- 22993691
TI  - Stability of climate networks with time.
AB  - The pattern of local daily fluctuations of climate fields such as temperatures
      and geopotential heights is not stable and hard to predict. Surprisingly, we find
      that the observed relations between such fluctuations in different geographical
      regions yields a very robust network pattern that remains highly stable during
      time. Using a new systematic methodology we track the origins of the network
      stability. It is found that about half of this network stability is due to the
      spatial 2D embedding of the network, and half is due to physical coupling between
      climate in different locations. We also find that around the equator, the
      contribution of the physical coupling is significantly less pronounced compared
      to off-equatorial regimes. Finally, we show that there is a gradual monotonic
      modification of the network pattern as a function of altitude difference.

PMID- 22993693
TI  - Constructions of two polycatenanes and one polypseudo-rotaxane by discrete
      tetrahedral cages and stool-like building units.
AB  - Mechanically Interlocked molecules, such as catenanes and rotaxanes, are of great
      interest due to their fascinating structures and potential applications, while
      such molecules have been mainly restricted to comprising components of
      interlocked rings or polygons. The constructions of infinite polycatenanes and
      polyrotaxanes by discrete cages remain great challenge, and only two infinite
      polycatenanes fabricated by discrete cages have been reported so far, while the
      structures of polyrotaxanes and polypseudo-rotaxanes fabricated by discrete build
      units have not been documented to date. Herein we report the first example of a
      two-dimensional (2D) polypseudo-rotaxane fabricated by stool-like build units,
      the second example of a one-dimensional (1D) polycatenane, and the second example
      of a three-dimensional (3D) polycatenane, which were assemblied by discrete
      tetrahedral cages. The pores of dehydrated 3D polycatenane are dynamic, and
      display size-dependent adsorption/desorption behaviors of alcohols.

PMID- 22993692
TI  - Cerebrospinal fluid metabolome in mood disorders-remission state has a unique
      metabolic profile.
AB  - Targeted metabolomics provides an approach to quantify metabolites involved in
      specific molecular pathways. We applied an electrochemistry-based, targeted
      metabolomics platform to define changes in tryptophan, tyrosine, purine and
      related pathways in the depressed and remitted phases of major depressive
      disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated
      depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared
      against those in healthy controls (n = 18; HC). The rMDD group showed differences
      in tryptophan and tyrosine metabolism relative to the other groups. The rMDD
      group also had higher methionine levels and larger methionine-to-glutathione
      ratios than the other groups, implicating methylation and oxidative stress
      pathways. The dMDD sample showed nonsignificant differences in the same direction
      in several of the metabolic branches assessed. The reductions in metabolites
      associated with tryptophan and tyrosine pathways in rMDD may relate to the
      vulnerability this population shows for developing depressive symptoms under
      tryptophan or catecholamine depletion.

PMID- 22993694
TI  - Quantum capacitance in topological insulators.
AB  - Topological insulators show unique properties resulting from massless, Dirac-like
      surface states that are protected by time-reversal symmetry. Theory predicts that
      the surface states exhibit a quantum spin Hall effect with counter-propagating
      electrons carrying opposite spins in the absence of an external magnetic field.
      However, to date, the revelation of these states through conventional transport
      measurements remains a significant challenge owing to the predominance of bulk
      carriers. Here, we report on an experimental observation of Shubnikov-de Haas
      oscillations in quantum capacitance measurements, which originate from
      topological helical states. Unlike the traditional transport approach, the
      quantum capacitance measurements are remarkably alleviated from bulk interference
      at high excitation frequencies, thus enabling a distinction between the surface
      and bulk. We also demonstrate easy access to the surface states at relatively
      high temperatures up to 60 K. Our approach may eventually facilitate an exciting
      exploration of exotic topological properties at room temperature.

PMID- 22993695
TI  - Functional integration between defence and IRE1-mediated ER stress response in
      rice.
AB  - Conditions within the endoplasmic reticulum (ER) influence most secretory
      proteins that pass through the ER. Therefore, eukaryotic cells must strike a
      balance between the ER stress response, which changes the conditions in the ER,
      and other considerations associated with protein secretion. Here, an interaction
      between the ER stress and defence responses in rice is described. Expression of
      OsWRKY45, which encodes a transcription factor that plays a central role in
      defence mediated by salicylic acid (SA), is induced by ER stress. Additionally,
      expression of some genes encoding pathogenesis-related (PR) secretory proteins is
      reduced by the ER stress response mediated by the stress sensor IRE1. Concomitant
      activation of the SA and ER stress responses suppresses the induction of ER
      stress-responsive genes, with the exception of OsWRKY45, and the reduction of PR
      gene expression. These findings demonstrate a functional integration between the
      defence and ER stress responses in plants.

PMID- 22993696
TI  - A seventh bacterial chlorophyll driving a large light-harvesting antenna.
AB  - The discovery of new chlorophyllous pigments would provide greater understanding
      of the mechanisms and evolution of photosynthesis. Bacteriochlorophyll f has
      never been observed in nature, although this name was proposed ~40 years ago
      based on structurally related compounds. We constructed a bacteriochlorophyll f
      accumulating mutant of the green sulfur bacterium Chlorobaculum limnaeum, which
      originally produced bacteriochlorophyll e, by knocking out the bchU gene encoding
      C-20 methyltransferase based on natural transformation. This novel pigment self
      aggregates in an in vivo light-harvesting antenna, the chlorosome, and exhibits a
      Q(y) peak of 705 nm, more blue-shifted than any other chlorosome reported so far;
      the peak overlaps the maximum (~700 nm) of the solar photon flux spectrum.
      Bacteriochlorophyll f chlorosomes can transfer light energy from core aggregated
      pigments to another bacteriochlorophyll in the chlorosomal envelope across an
      energy gap of ~100 nm, and is thus a promising material for development of new
      bioenergy applications.

PMID- 22993698
TI  - Stygoregions--a promising approach to a bioregional classification of groundwater
      systems.
AB  - Linked to diverse biological processes, groundwater ecosystems deliver essential
      services to mankind, the most important of which is the provision of drinking
      water. In contrast to surface waters, ecological aspects of groundwater systems
      are ignored by the current European Union and national legislation. Groundwater
      management and protection measures refer exclusively to its good physicochemical
      and quantitative status. Current initiatives in developing ecologically sound
      integrative assessment schemes by taking groundwater fauna into account depend on
      the initial classification of subsurface bioregions. In a large scale survey, the
      regional and biogeographical distribution patterns of groundwater dwelling
      invertebrates were examined for many parts of Germany. Following an exploratory
      approach, our results underline that the distribution patterns of invertebrates
      in groundwater are not in accordance with any existing bioregional classification
      system established for surface habitats. In consequence, we propose to develope a
      new classification scheme for groundwater ecosystems based on stygoregions.

PMID- 22993697
TI  - Reconstruction of the polar interface between hexagonal LuFeO3 and intergrown
      Fe3O4 nanolayers.
AB  - We report the observation of an unusual phase assembly behavior during the growth
      of hexagonal LuFeO(3) thin films which resulted in the formation of epitaxial
      Fe(3)O(4) nanolayers. The magnetite layers were up to 5 nm thick and grew under
      the conditions at which Fe(2)O(3) is thermodynamically stable. These Fe(3)O(4)
      nanolayers act as buffer layers promoting a highly epitaxial growth of the
      hexagonal LuFeO(3) thin film up to 150 nm thick. Using scanning transmission
      electron microscopy, we show that the interface between (001) LuFeO(3) and (111)
      Fe(3)O(4) can be reconstructed in two ways depending on the sequence in which
      these compounds grow on each other. We suggest the polarity of the interface is
      the reason behind the observed interface reconstruction and epitaxial
      stabilization of magnetite.

PMID- 22993699
TI  - Linear and passive silicon optical isolator.
AB  - On-chip optical isolation plays a key role in optical communications and
      computing based on silicon integrated photonic structures and has attracted great
      attentions for long years. Recently there have appeared hot controversies upon
      whether isolation of light can be realized via linear and passive photonic
      structures. Here we demonstrate optical isolation of infrared light in purely
      linear and passive silicon photonic structures. Both numerical simulations and
      experimental measurements show that the round-trip transmissivity of in-plane
      infrared light across a silicon photonic crystal slab heterojunction diode could
      be two orders of magnitudes smaller than the forward transmissivity at around
      1,550 nm with a bandwidth of about 50 nm, indicating good performance of optical
      isolation. The occurrence of in-plane light isolation is attributed to the
      information dissipation due to off-plane and side-way scattering and selective
      modal conversion in the multiple-channel structure and has no conflict with the
      reciprocal principle.

PMID- 22993700
TI  - Risk factors for repeat abdominal surgery in patients with Crohn's disease.

PMID- 22993701
TI  - Current issues involving the treatment of small rectal carcinoid tumors.

PMID- 22993702
TI  - Clinical significance of serum carcinoembryonic antigen level in rectal cancer
      patients who underwent preoperative chemoradiotherapy.

PMID- 22993703
TI  - An update on preoperative radiotherapy for locally advanced rectal cancer.
AB  - Even in patients undergoing an optimal surgical technique (e.g., total mesorectal
      excision), radiotherapy provides a significant benefit in the local control of
      rectal cancer. Compared with postoperative treatment, chemoradiotherapy given
      preoperatively has been shown to decrease local recurrence rates and toxicity.
      Additionally, preoperative chemoradiotherapy permits the early identification of
      tumor responses to this cytotoxic treatment by surgical pathology. Pathological
      parameters reflecting the tumor response to chemoradiotherapy have been shown to
      be surrogate markers for long-term clinical outcomes. Post-chemoradiotherapy
      downstaging from cStage II-III to ypStage 0-I indicates a favorable prognosis,
      with no difference between ypStage 0 and ypStage I. Research is ongoing to
      develop useful tools (clinical, molecular, and radiological) for clinical
      determination of the pathologic chemoradiotherapeutic response before surgery,
      and possibly even before preoperative treatment. In the future, risk-adapted
      strategies, including intensification of preoperative therapy, conservative
      surgery, or the selective administration of postoperative chemotherapy, will be
      realized for locally-advanced rectal cancer patients based on their response to
      preoperative chemoradiotherapy.

PMID- 22993704
TI  - Risk factors for repeat abdominal surgery in korean patients with Crohn's
      disease: a multi-center study of a korean inflammatory bowel disease study group.
AB  - PURPOSE: The purpose of this study was to assess the risk factors for repeated
      abdominal surgery in Crohn's disease (CD) patients after the first abdominal
      surgery. Prior studies have tried to identify the risk factors for postoperative
      recurrence in CD patients, but the results of the studies have been inconsistent.
      Furthermore, few data on the risk factors for repeated abdominal surgery are
      available. METHODS: Clinical data on CD patients who underwent abdominal surgery
      from January 2000 to December 2009 were collected from seventeen university
      hospitals and one colorectal clinic. Data from a total of 708 patients were
      analyzed to find the risk factors for repeated abdominal surgery in CD patients.
      The mean follow-up period was 72 months. RESULTS: The risk of repeated abdominal
      surgery was 3 times higher in young patients (below 16 years old) than in older
      patients (odds ratio [OR], 3.056; 95% confidence interval [CI], 1.021 to 9.150);
      P = 0.046). Stricturing behavior at diagnosis was also a risk factor for repeated
      abdominal surgery (OR, 2.438; 95% CI, 1.144 to 5.196; P = 0.021). Among operative
      indications, only intra-abdominal abscess was associated with repeated abdominal
      surgery (OR, 2.393; 95% CI, 1.098 to 5.216; P = 0.028). Concerning type of
      operation, an ileostomy might be a risk factor for repeated abdominal surgery
      (OR, 11.437; 95% CI, 1.451 to 90.124; P = 0.021). Emergency surgery (OR, 4.994;
      95% CI, 2.123 to 11.745; P < 0.001) and delayed diagnosis after surgery (OR,
      2.339; 95% CI, 1.147 to 4.771; P = 0.019) also increased the risk of repeated
      abdominal surgery. CONCLUSION: Young age (below 16 years), stricturing behavior,
      intra-abdominal abscess, emergency surgery, and delayed diagnosis after surgery
      were identified as possible risk factors for repeated abdominal surgery in CD
      patients.

PMID- 22993705
TI  - An analysis of factors associated with increased perineal descent in women.
AB  - PURPOSE: Treatment of descending perineal syndrome is focused on personal
      etiology and on improving symptoms. However, the etiology of increased perineal
      descent (PD) is unclear. Therefore, the aim of the present study was to evaluate
      factors associated with increased resting and dynamic PD in women. METHODS: From
      January 2004 to August 2010, defecographic findings in 201 female patients were
      reviewed retrospectively. Patient's age, surgical history, manometric results and
      defecographic findings were compared with resting and dynamic PD. RESULTS: Age (P
      < 0.01), number of vaginal deliveries (P < 0.01) and resting anorectal angle (P <
      0.01) were correlated with increased resting PD. Also, findings of rectoceles (P
      < 0.05) and intussusceptions (P < 0.05) were significantly correlated with
      increased resting PD. On the other hand, increased dynamic PD was correlated with
      age (P < 0.05), resting anal pressure (P < 0.01) and sigmoidoceles (P < 0.05). No
      significant correlation existed between non-relaxing puborectalis, history of
      pelvic surgery and increased PD. Also, no significant differences in PD according
      to the symptoms were observed. CONCLUSION: Increased number of vaginal deliveries
      and increased resting rectoanal angle are associated with increased resting PD
      whereas increased resting anal pressure is correlated with increased dynamic PD.
      Older age correlates with both resting and dynamic PD. Defecographic findings,
      such as rectoceles and intussusceptions, are associated with resting PD, and
      sigmoidoceles correlated with dynamic PD. These results can serve as foundational
      research for understanding the pathophysiology and causes of increasing PD in
      women better and for finding a fundamental method of treatment.

PMID- 22993706
TI  - Transanal endoscopic microsurgery for the treatment of well-differentiated rectal
      neuroendocrine tumors.
AB  - PURPOSE: Recently, an increase in well-differentiated rectal neuroendocrine
      tumors (WRNETs) has been noted. We aimed to evaluate transanal endoscopic
      microsurgery (TEM) for the treatment of WRNETs. METHODS: Between December 1995
      and August 2009, 109 patients with WRNETs underwent TEM. TEM was performed for
      patients with tumors sizes of up to 20 mm and without a lymphadenopathy. These
      patients had been referred from other clinics after having been diagnosed with
      WRNETs by using a colonoscopic biopsy; they had undergone a failed endoscopic
      submucosal dissection (ESD) or endoscopic mucosal resection (EMR) and exhibited
      an involved resection margin and remaining tumor after ESD or EMR, regardless of
      the distance from the anal verge. This study included 38 patients that had more
      than three years of follow-up. RESULTS: The mean age of the patients was 51.3 +/-
      11.9 years, the mean tumor size was 8.0 +/- 3.9 mm, and no morbidity occurred.
      Thirty-five patients were asymptomatic. TEM was performed after a colonoscopic
      resection in 13 cases because of a positive resection margin, a residual tumor or
      a non-lifting lesion. Complete resections were performed in 37 patients; one
      patient with a positive margin was considered surgically complete. In one
      patient, liver metastasis and a recurrent mesorectal node occurred after five and
      10 years, respectively. CONCLUSION: TEM might provide an accessible and effective
      treatment either as an initial or as an adjunct after a colonoscopic resection
      for a WRNET.

PMID- 22993707
TI  - Clinical significance of serial serum carcinoembryonic antigen values for
      treating rectal cancer with preoperative chemoradiotherapy.
AB  - PURPOSE: Preoperative chemoradiotherapy is now widely accepted to treat rectal
      cancer; however, the prognosis for rectal cancer patients during and after
      chemoradiotherapy must be determined. The aim of this study was to evaluate the
      serial serum carcinoembryonic antigen (s-CEA) samples in patients with rectal
      cancer who underwent radical surgery after concurrent chemoradiotherapy (CRT).
      METHODS: This study evaluated 236 patients with rectal cancer who received
      preoperative CRT followed by curative surgery between June 2005 and June 2010. We
      measured the patient's s-CEA levels pre-CRT, post-CRT and post-surgery. Patients
      were classified into four groups according to their s-CEA concentrations (group
      1, high, high, high; group 2, high, high, normal; group 3, high, normal, normal;
      group 4, normal, normal, normal). We analyzed the clinicopathologic factors and
      the outcomes among these groups. RESULTS: Of the 236 patients, 12 were in group
      1, 31 were in group 2, 67 were in group 3, and 126 were in group 4. The 3-year
      disease-free survival rate in group 1 was poorer than those in group 3 (P =
      0.007) and group 4 (P < 0.001). In a univariate analysis, type of surgery,
      clinical N stage, pathologic T or N stage, lymphovascular invasion, perineural
      invasion, and CEA group were prognostic factors. A multivariate analysis revealed
      that type of surgery, pathologic T stage, and lymphovascular invasion were
      independent prognostic factors; however, no statistical significance was
      associated with the CEA group. CONCLUSION: High pre-CRT, post-CRT, and post
      surgery s-CEA levels in patients with rectal cancer were associated with high
      rates of systemic recurrence and poor survival. Therefore, patients with
      sustained high s-CEA levels during CRT require careful monitoring after surgery.

PMID- 22993708
TI  - Incidence and Multiplicities of Adenomatous Polyps in TNM Stage I Colorectal
      Cancer in Korea.
AB  - PURPOSE: In recent years, the incidence of early-stage colorectal cancer (CRC)
      has markedly increased in the population within the Republic of Korea. The aim of
      this study was to evaluate the clinicopathologic features of adenomatous polyps
      in TNM stage I CRC patients and in the general population. METHODS: Between March
      2003 and September 2009, 168 patients with stage I CRC were enrolled in this
      study. In addition, the records of 4,315 members of the general population
      without CRC, as determined by colonoscopy during a health check-up, were
      reviewed. RESULTS: Of the 168 patients with stage I CRC, 68 (40.5%) had
      coexisting colorectal adenomatous polyps and of the 4,315 members of the general
      population, 1,112 (26.0%) had coexisting adenomatous polyps (P = 0.006). The
      prevalences of adenomatous polyp multiplicity in early CRC and in the general
      population were 32% and 15%, respectively (P = 0.023). Patients with coexisting
      adenomatous polyps had a higher frequency of tubulovillous or villous adenomas
      than members of the general population with polyps (7.5% vs. 2.0%, P = 0.037).
      Furthermore, a subgroup analysis showed that the occurrence (44% vs. 34%, P =
      0.006) and the multiplicity (32% vs. 15%, P = 0.023) of adenomatous polyps were
      greater for T2 than T1 cancer. CONCLUSION: The prevalence and the multiplicity of
      adenomatous polyps in TNM stage I CRC is higher than it is in the general
      population. The findings of this study suggest that depth of invasion of early
      stage CRC affects the prevalence and the number of adenomatous polyps in the
      remaining colon and rectum.

PMID- 22993709
TI  - Anal myolipoma: a new benign entity in patients with an anal tumor?
AB  - A myolipoma is an extremely rare benign neoplasm, occurring most frequently in
      adults in the deep soft tissue of the abdomen or retroperitoneum. We experienced
      a case of an anal myolipoma occurring in a 30-year-old woman, and it was
      surgically resected. To our knowledge, this is the first reported case of a
      myolipoma arising from the anus, so such a possibility needs to be considered in
      the differential diagnosis.

PMID- 22993710
TI  - A case of a mucinous adenocarcinoma arising from a rectal diverticulum.
AB  - The occurrence of an adenocarcinoma arising from a rectal diverticulum that
      causes mechanical ileus is very rare. Recently, we diagnosed a case of a mucinous
      adenocarcinoma in a rectal diverticulum after an emergent abdominal perineal
      resection and permanent colostomy by laparotomy. Here, we present a case report
      and a review of the literature.

PMID- 22993711
TI  - Antimicrobial-resistant Bacteria: An Unrecognized Work-related Risk in Food
      Animal Production.
AB  - The occupations involved in food animal production have long been recognized to
      carry significant health risks for workers, with special attention to injuries.
      However, risk of pathogen exposure in these occupations has been less extensively
      considered. Pathogens are a food safety issue and are known to be present
      throughout the food animal production chain. Workers employed at farms and
      slaughterhouses are at risk of pathogen exposure and bacterial infections. The
      industrialization of animal farming and the use of antimicrobials in animal feed
      to promote growth have increased the development of antimicrobial resistance. The
      changed nature of these pathogens exposes workers in this industry to new
      strains, thus modifying the risks and health consequences for these workers.
      These risks are not yet recognized by any work-related health and safety agency
      in the world.

PMID- 22993712
TI  - Application of pharmacovigilance methods in occupational health surveillance:
      comparison of seven disproportionality metrics.
AB  - OBJECTIVES: The French National Occupational Diseases Surveillance and Prevention
      Network (RNV3P) is a French network of occupational disease specialists, which
      collects, in standardised coded reports, all cases where a physician of any
      specialty, referred a patient to a university occupational disease centre, to
      establish the relation between the disease observed and occupational exposures,
      independently of statutory considerations related to compensation. The objective
      is to compare the relevance of disproportionality measures, widely used in
      pharmacovigilance, for the detection of potentially new disease * exposure
      associations in RNV3P database (by analogy with the detection of potentially new
      health event * drug associations in the spontaneous reporting databases from
      pharmacovigilance). METHODS: 2001-2009 data from RNV3P are used (81,132
      observations leading to 11,627 disease * exposure associations). The structure of
      RNV3P database is compared with the ones of pharmacovigilance databases. Seven
      disproportionality metrics are tested and their results, notably in terms of
      ranking the disease * exposure associations, are compared. RESULTS: RNV3P and
      pharmacovigilance databases showed similar structure. Frequentist methods
      (proportional reporting ratio [PRR], reporting odds ratio [ROR]) and a Bayesian
      one (known as BCPNN for "Bayesian Confidence Propagation Neural Network") show a
      rather similar behaviour on our data, conversely to other methods (as Poisson).
      Finally the PRR method was chosen, because more complex methods did not show a
      greater value with the RNV3P data. Accordingly, a procedure for detecting signals
      with PRR method, automatic triage for exclusion of associations already known,
      and then investigating these signals is suggested. CONCLUSION: This procedure may
      be seen as a first step of hypothesis generation before launching epidemiological
      and/or experimental studies.

PMID- 22993713
TI  - Allergic to pool water.
AB  - To identify the allergy problem of a 36-year old swimming instructor, who
      experiences heavy itching and rashes whenever she comes in contact with pool
      water. Patch tests were performed with European standard series and materials
      from the work floor. A positive patch test to aluminum chloride and flocculant
      was observed. Occupational dermatitis is, based on a contact allergy to aluminum
      chloride in the flocculant.

PMID- 22993714
TI  - Can we reduce workplace fatalities by half?
AB  - Singapore, an island republic of over 5 million inhabitants, has 3.1 million
      workers. Most are employed in the service, finance and tourist/transport
      industry. Significant numbers work in manufacturing, construction and heavy
      industry. Following a series of construction and shipyard accidents with multiple
      deaths in 2004, the government announced its intention to reduce workplace
      fatalities from 4.9 to 2.5 per 100,000 by 2015. There was strong political will
      to achieve this target. The strategic approaches were to build workplace safety
      and health (WSH) capabilities; implement legislative changes with enforcement;
      promote benefits of WSH and recognize best practices, and enhance partnership
      with stakeholders. The anticipated outcomes were to reduce workplace fatality and
      injury rates; have WSH as an integral part of business; and establish a
      progressive and pervasive WSH culture. With these measures, the workplace
      fatality rate declined from 4.9/100,000 in 2004, to 2.2/100,000 in 2010. However,
      other confounding factors could also account for this decline, and have to be
      considered. The next target, announced by Singapore's Prime Minister in 2008, is
      to further reduce the workplace fatality rate to 1.8/100,000 by 2018, and to have
      "one of the best workplace safety records in the world".

PMID- 22993715
TI  - When Work is Related to Disease, What Establishes Evidence for a Causal Relation?
AB  - Establishing a causal relationship between factors at work and disease is
      difficult for occupational physicians and researchers. This paper seeks to
      provide arguments for the judgement of evidence of causality in observational
      studies that relate work factors to disease. I derived criteria for the judgement
      of evidence of causality from the following sources: the criteria list of Hill,
      the approach by Rothman, the methods used by International Agency for Research on
      Cancer (IARC), and methods used by epidemiologists. The criteria are applied to
      two cases of putative occupational diseases; breast cancer caused by shift work
      and aerotoxic syndrome. Only three of the Hill criteria can be applied to an
      actual study. Rothman stresses the importance of confounding and alternative
      explanations than the putative cause. IARC closely follows Hill, but they also
      incorporate other than epidemiological evidence. Applied to shift work and breast
      cancer, these results have found moderate evidence for a causal relationship, but
      applied to the aerotoxic syndrome, there is an absence of evidence of causality.
      There are no ready to use algorithms for judgement of evidence of causality.
      Criteria from different sources lead to similar results and can make a conclusion
      of causality more or less likely.

PMID- 22993716
TI  - Return to work after an acute coronary syndrome: patients' perspective.
AB  - OBJECTIVES: To describe the time perspective of return to work and the factors
      that facilitate and hinder return to work in a group of survivors of acute
      coronary syndrome (ACS). METHODS: Retrospective semi-structured telephone survey
      2 to 3 years after hospitalization with 84 employed Dutch ACS-patients from one
      academic medical hospital. RESULTS: Fifty-eight percent of patients returned to
      work within 3 months, whereas at least 88% returned to work once within 2 years.
      Two years after hospitalization, 12% of ACS patients had not returned to work at
      all, and 24% were working, but not at pre-ACS levels. For all ACS-patients, the
      most mentioned categories of facilitating factors to return to work were having
      no complaints and not having signs or symptoms of heart disease. Physical
      incapacity, co-morbidity, and mental incapacity were the top 3 categories of
      hindering factors against returning to work. CONCLUSION: Within 2 years, 36% of
      the patients had not returned to work at their pre-ACS levels. Disease factors,
      functional capacity, environmental factors, and personal factors were listed as
      affecting subjects' work ability level.

PMID- 22993717
TI  - Evaluation of occupational health teaching sessions for final year medical
      students.
AB  - OBJECTIVES: The study was conducted with the aim of evaluating applied
      occupational health teaching for final-year medical students at Hacettepe
      University, Faculty of Medicine. METHODS: The study included all sixth grade
      medical students (n=293) during one academic year. Pre- and post-training tests
      were used to assess the magnitude of change in knowledge and attitude of students
      on occupational health, whereas the opinion of students on several aspects of the
      quality of teaching sessions were assessed by using post-training questionnaires.
      RESULTS: Post-training tests revealed that the level of knowledge on all aspects
      of occupational health increased among medical students. An evaluation of the
      teaching sessions showed favorable results for the overall quality of the
      sessions: 81.3% of the students stated that the sessions were well organized,
      81.7% remarked the workplace/factory visit was a valuable experience, and 91.0%
      stated feeling more competent on occupational health issues. CONCLUSION: There
      was a greater increase in students' knowledge on technical precautions than their
      knowledge on issues related to medical practice in the workplace. Visiting a
      workplace was found to contribute to the overall aim of knowledge and attitude
      change on occupational health issues. The scope of undergraduate medical
      education should be extended by improving occupational health education with
      respect to educational content, duration, and methods.

PMID- 22993718
TI  - Work environments and exposure to hazardous substances in korean tire
      manufacturing.
AB  - OBJECTIVES: The purpose of this study is to evaluate the tire manufacturing work
      environments extensively and to identify workers' exposure to hazardous
      substances in various work processes. METHODS: Personal air sampling was
      conducted to measure polycyclic aromatic hydrocarbons, carbon disulfide, 1,3
      butadiene, styrene, methyl isobutyl ketone, methylcyclohexane, formaldehyde,
      sulfur dioxide, and rubber fume in tire manufacturing plants using the National
      Institute for Occupational Safety Health Manual of Analytical Methods. Noise,
      carbon monoxide, and heat stress exposure were evaluated using direct reading
      instruments. Past concentrations of rubber fume were assessed using regression
      analysis of total particulate data from 2003 to 2007, after identifying the
      correlation between the concentration of total particulate and rubber fume.
      RESULTS: Workers were exposed to rubber fume that exceeded 0.6 mg/m(3), the
      maximum exposure limit of the UK, in curing and production management processes.
      Forty-seven percent of workers were exposed to noise levels exceeding 85 dBA.
      Workers in the production management process were exposed to 28.1C (wet bulb
      globe temperature value, WBGT value) even when the outdoor atmosphere was 2.7C
      (WBGT value). Exposures to other substances were below the limit of detection or
      under a tenth of the threshold limit values given by the American Conference of
      Governmental Industrial Hygienists. CONCLUSION: To better classify exposure
      groups and to improve work environments, examining closely at rubber fume
      components and temperature as risk indicators in tire manufacturing is
      recommended.

PMID- 22993719
TI  - The Experience of Miners Relocated to Alternative Positions due to Silicosis in
      the Andean of CODELCO, Chile, 2010.
AB  - OBJECTIVES: To understand the personal experiences of mine workers that have
      experienced job relocation due to silicosis at the Andina Division of Corporacion
      Nacional del Cobre (CODELCO), Chile. The purpose of the study was to provide
      useful information for the development of new local, business and public policies
      for the care of workers with silicosis. METHODS: A qualitative study based on a
      practical case study of 5 workers. The information was collected by means of
      structured individual interviews. The method of analysis was phenomenology.
      RESULTS: The corporal axis was the most commented upon. It included awareness of
      the illness, body pains, fatigue, and antagonistic mood disorders (sadness, or
      the difficulty in finding meaning in life). As far as personal relationships,
      there was evidence of strong relationships with family, coworkers and friends, as
      well as extended family. Over all, the experience of relocation was positive with
      periods of impatience and uncertainty. The job reassignment provided a new and
      pleasant context for the relocated workers and in the process improved their
      perception of their quality of life. CONCLUSIONS: A multidisciplinary team should
      attend mine workers relocated because of silicosis by addressing the mental and
      physical aspects of their disease, along with the integral participation of close
      family members. It is suggested that this investigation be maintain over time to
      record the personal experiences in the medium-term, adding new cases with the
      intention of shedding more light on the phenomenon being studied. As a preventive
      measure, continual workshops are needed on the proper use of respiratory
      protection in addition, a group of monitors is required.

PMID- 22993720
TI  - Discomfort analysis in computerized numeric control machine operations.
AB  - OBJECTIVES: The introduction of computerized numeric control (CNC) technology in
      manufacturing industries has revolutionized the production process, but there are
      some health and safety problems associated with these machines. The present study
      aimed to investigate the extent of postural discomfort in CNC machine operators,
      and the relationship of this discomfort to the display and control panel height,
      with a view to validate the anthropometric recommendation for the location of the
      display and control panel in CNC machines. METHODS: The postural discomforts
      associated with CNC machines were studied in 122 male operators using Corlett and
      Bishop's body part discomfort mapping, subject information, and discomfort level
      at various time intervals from starting to end of a shift. This information was
      collected using a questionnaire. Statistical analysis was carried out using
      ANOVA. RESULTS: Neck discomfort due to the positioning of the machine displays,
      and shoulder and arm discomfort due to the positioning of controls were
      identified as common health issues in the operators of these machines. The study
      revealed that 45.9% of machine operators reported discomfort in the lower back,
      41.8% in the neck, 22.1% in the upper-back, 53.3% in the shoulder and arm, and
      21.3% of the operators reported discomfort in the leg. CONCLUSION: Discomfort
      increased with the progress of the day and was highest at the end of a shift;
      subject age had no effect on patient tendency to experience discomfort levels.

PMID- 22993721
TI  - Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity.
AB  - AIMS: To determine whether specific IgE and skin prick test correlate better in
      predicting reaction severity during a double-blinded placebo controlled food
      challenge (DBPCFC) for egg, milk, and multiple tree nut allergens.  STUDY DESIGN:
      Prospective study.  PLACE AND DURATION OF STUDY: Department of Pediatrics,
      Stanford University School of Medicine, August 2009 and ongoing.  METHODOLOGY: We
      examined the reaction severity of twenty-four subjects to nine possible food
      allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut.
      Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were
      classified into mild (1), moderate (2), or severe (3) reactions using a modified
      Bock's criteria.  RESULTS: Twenty four subjects underwent a total of 80 DBPCFC.
      Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%,
      were classified as mild. No reactions occurred with a SPT of zero mm while three
      reactions occurred with a negative specific IgE. All reactions were reversible
      with medication.  CONCLUSION: These data suggest that SPT and specific IgE levels
      are not associated with reaction severity (p<0.64 and 0.27, respectively). We
      also found that combining specific IgE and SPT improved specificity but did not
      help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a
      sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7
      resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis
      70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2).

PMID- 22993723
TI  - A case of collagenous gastroenteritis with pseudomembranes.

PMID- 22993724
TI  - Postpartum onset of adult celiac disease in identical twin sisters.

PMID- 22993725
TI  - Origins of the Canadian Association for the Study of the Liver: A personal
      memoir.
AB  - The Canadian Association for the Study of the Liver (CASL) (Association
      Canadienne Pour L'Etude Du Foie) is a thriving organization. Although it was
      established more than a quarter of a century ago and has been successful since
      the beginning, most members are unaware of how CASL came into being or of its
      humble origins as a precursor club in the 1970s. The present article reviews
      those early days. It is written as a memoir because of the author's personal
      involvement and is based on detailed records, correspondence and handwritten
      notes from that era.

PMID- 22993722
TI  - Evolution of microbes and viruses: a paradigm shift in evolutionary biology?
AB  - When Charles Darwin formulated the central principles of evolutionary biology in
      the Origin of Species in 1859 and the architects of the Modern Synthesis
      integrated these principles with population genetics almost a century later, the
      principal if not the sole objects of evolutionary biology were multicellular
      eukaryotes, primarily animals and plants. Before the advent of efficient gene
      sequencing, all attempts to extend evolutionary studies to bacteria have been
      futile. Sequencing of the rRNA genes in thousands of microbes allowed the
      construction of the three- domain "ribosomal Tree of Life" that was widely
      thought to have resolved the evolutionary relationships between the cellular life
      forms. However, subsequent massive sequencing of numerous, complete microbial
      genomes revealed novel evolutionary phenomena, the most fundamental of these
      being: (1) pervasive horizontal gene transfer (HGT), in large part mediated by
      viruses and plasmids, that shapes the genomes of archaea and bacteria and call
      for a radical revision (if not abandonment) of the Tree of Life concept, (2)
      Lamarckian-type inheritance that appears to be critical for antivirus defense and
      other forms of adaptation in prokaryotes, and (3) evolution of evolvability,
      i.e., dedicated mechanisms for evolution such as vehicles for HGT and stress
      induced mutagenesis systems. In the non-cellular part of the microbial world,
      phylogenomics and metagenomics of viruses and related selfish genetic elements
      revealed enormous genetic and molecular diversity and extremely high abundance of
      viruses that come across as the dominant biological entities on earth.
      Furthermore, the perennial arms race between viruses and their hosts is one of
      the defining factors of evolution. Thus, microbial phylogenomics adds new
      dimensions to the fundamental picture of evolution even as the principle of
      descent with modification discovered by Darwin and the laws of population
      genetics remain at the core of evolutionary biology.

PMID- 22993726
TI  - 'Doing the twist': insight gained from spiral enteroscopy.

PMID- 22993727
TI  - Incomplete colonoscopy: maximizing completion rates of gastroenterologists.
AB  - BACKGROUND: Cecal intubation is one of the goals of a quality colonoscopy;
      however, many factors increasing the risk of incomplete colonoscopy have been
      implicated. The implications of missed pathology and the demand on health care
      resources for return colonoscopies pose a conundrum to many physicians. The
      optimal course of action after incomplete colonoscopy is unclear. OBJECTIVES: To
      assess endoscopic completion rates of previously incomplete colonoscopies, the
      methods used to complete them and the factors that led to the previous incomplete
      procedure. METHODS: All patients who previously underwent incomplete colonoscopy
      (2005 to 2010) and were referred to St Paul's Hospital (Vancouver, British
      Columbia) were evaluated. Colonoscopies were re-attempted by a single
      endoscopist. Patient charts were reviewed retrospectively. RESULTS: A total of 90
      patients (29 males) with a mean (+/- SD) age of 58 +/- 13.2 years were included
      in the analysis. Thirty patients (33%) had their initial colonoscopy performed by
      a gastroenterologist. Indications for initial colonoscopy included surveillance
      or screening (23%), abdominal pain (15%), gastrointestinal bleeding (29%), change
      in bowel habits or constitutional symptoms (18%), anemia (7%) and chronic
      diarrhea (8%). Reasons for incomplete colonoscopy included poor preparation
      (11%), pain or inadequate sedation (16%), tortuous colon (30%), diverticular
      disease (6%), obstructing mass (6%) and stricturing disease (10%). Reasons for
      incomplete procedures in the remaining 21% of patients were not reported by the
      referring physician. Eighty-seven (97%) colonoscopies were subsequently completed
      in a single attempt at the institution. Seventy-six (84%) colonoscopies were
      performed using routine manoeuvres, patient positioning and a variable-stiffness
      colonoscope (either standard or pediatric). A standard 160 or 180 series Olympus
      gastroscope (Olympus, Japan) was used in five patients (6%) to navigate through
      sigmoid diverticular disease; a pediatric colonoscope was used in six patients
      (7%) for similar reasons. Repeat colonoscopy on the remaining three patients (3%)
      failed: all three required surgery for strictures (two had obstructing malignant
      masses and one had a severe benign obstructing sigmoid diverticular stricture).
      CONCLUSION: Most patients with previous incomplete colonoscopy can undergo a
      successful repeat colonoscopy at a tertiary care centre with instruments that are
      readily available to most gastroenterologists. Other modalities for evaluation of
      the colon should be deferred until a second attempt is made at an expert centre.

PMID- 22993728
TI  - An audit of influenza vaccination status in adults with inflammatory bowel
      disease.
AB  - BACKGROUND: Several guidelines recommend influenza vaccination for high-risk
      patients, including those on immune-suppressing medications (IS). OBJECTIVE: To
      assess the vaccination status and immunization history of an outpatient
      inflammatory bowel disease (IBD) population for H1N1 and seasonal influenza.
      RESULTS: Among 250 patients, 104 (41.6%) had been immunized against H1N1 and 62
      (24.8%) against seasonal influenza, and 158 (63.2%) were taking IS (azathioprine,
      6-mercaptopurine, infliximab, adalimumab, methotrexate, cyclosporine or
      prednisone). Among subjects on IS, the presence of comorbidities warranting
      vaccination was associated with higher likelihood of H1N1 immunization (62.5%
      versus 35.8%; P=0.022) but not of seasonal influenza vaccination (25.0% versus
      17.2%; P=0.392). Among patients without comorbidities warranting vaccination, IS
      was associated with a decreased likelihood of vaccination against seasonal
      influenza (17.2% versus 30.7%; P=0.036) but not H1N1 (35.8% versus 41.3%;
      P=0.46). The frequency of H1N1 vaccination was significantly higher among
      patients who visited a general practitioner at least once yearly (45.7% versus
      20%; P=0.0027), with a similar trend for seasonal influenza vaccination (27.1%
      versus 12.5%; P=0.073). Among 91 patients on IS who declined vaccination, 39.6%
      reported fear of immediate side effects, 29.7% reported concerns about developing
      serious medical complications, 15.4% reported concerns about activating IBD and
      15.4% were not aware that vaccination was indicated. CONCLUSIONS: Current
      strategies for vaccinating IBD patients on IS are inadequate. Primary care
      provider education, incentive programs and regular primary care contact may
      improve immunization uptake.

PMID- 22993729
TI  - The impact of hepatitis B knowledge and stigma on screening in Canadian Chinese
      persons.
AB  - BACKGROUND: Chronic hepatitis B (CHB) infection is endemic in East Asia, and
      those who emigrate to North America have higher rates of CHB infection when
      compared with the general population. To date, Chinese persons residing in Canada
      have not been mandated to be screened for CHB infection. OBJECTIVE: To understand
      factors that influence hepatitis B screening behaviour among the Chinese
      community in Toronto, Ontario, and to determine whether stigma acts as a barrier
      to screening. METHODS: Self-identified Chinese individuals at a family
      physician's office and at English as a second language (ESL) classes in Toronto
      completed a questionnaire with demographic questions, a hepatitis B virus (HBV)
      stigma scale and an HBV knowledge scale. Pearson product moment correlation and
      multiple regression techniques were used to analyze the data. RESULTS: The study
      group included 343 individuals. Their mean (+/- SD) age was 48.76 +/- 17.49 years
      and the majority were born in China (n=229 [68%]). The mean score on the HBV
      knowledge scale was 10.13 +/- 1.76 (range 0 to 15), with higher scores indicating
      greater HBV knowledge. The mean score on the stigma scale was 54.60 +/- 14.18
      (range 20 to 100), with higher scores indicating more stigma. Being an immigrant,
      having a family physician and having greater knowledge of HBV were associated
      with increased rates of screening for this infection. In contrast, greater levels
      of HBV stigma were associated with decreased likelihood of screening for HBV
      infection. CONCLUSIONS: HBV stigma is associated with reduced rates of screening
      for this infection.

PMID- 22993730
TI  - Hyperamylasemia and pancreatitis following spiral enteroscopy.
AB  - BACKGROUND: Acute pancreatitis is a significant potential complication with
      double-balloon enteroscopy. Hyperamylasemia is frequently observed after both
      double-balloon enteroscopy and single-balloon enteroscopy but often without
      associated pancreatitis. Whether the same phenomenon occurs with spiral
      enteroscopy is currently unknown. AIMS: To determine the incidence of
      pancreatitis and hyperamylasemia following spiral enteroscopy. METHODS: A
      prospective cohort study of consecutive patients undergoing proximal spiral
      enteroscopy was conducted. Serum amylase levels were measured immediately before
      and following the procedure, combined with observation for clinical signs of
      pancreatitis. RESULTS: A total of 32 patients underwent proximal spiral
      enteroscopy, with a mean total procedure time of 51 min (range 30 min to 100 min)
      and mean depth of insertion of 240 cm (range 50 cm to 350 cm). The diagnostic
      yield was 50%, with 31% of all procedures being therapeutic. While no patients
      exhibited signs that raised suspicion of pancreatitis, hyperamylasemia was common
      (20%). Hyperamylasemia was not significantly associated with procedure duration
      or depth of insertion but was linked to patients with Peutz-Jeghers syndrome and
      with the use of propofol sedation, suggesting that it may be more common in
      difficult cases. CONCLUSIONS: Postprocedural hyperamylasemia occurred frequently
      with proximal spiral enteroscopy, while no associated pancreatitis was observed.
      This finding suggests that hyperamylasemia may not necessarily reflect pancreatic
      injury nor portend a risk for pancreatitis.

PMID- 22993731
TI  - Endoscopic management of biliary complications following liver transplantation
      after donation from cardiac death donors.
AB  - BACKGROUND: Previous studies have shown a higher incidence of biliary
      complications following donation after cardiac death (DCD) liver transplantation
      compared with donation after brain death (DBD) liver transplantation. The
      endoscopic management of ischemic type biliary strictures in patients who have
      undergone DCD liver transplants needs to be characterized further. METHODS: A
      retrospective institutional review of all patients who underwent DCD liver
      transplant from January 2006 to September 2011 was performed. These patients were
      compared with all patients who underwent DBD liver transplantation in the same
      time period. A descriptive analysis of all DCD patients who developed biliary
      complications and their subsequent endoscopic management was also performed.
      RESULTS: Of the 36 patients who received DCD liver transplants, 25% developed
      biliary complications compared with 13% of patients who received DBD liver
      transplants (P=0.062). All DCD allograft recipients who developed biliary
      complications became symptomatic within three months of transplantation. Ischemic
      type biliary strictures in DCD allograft recipients included disseminated biliary
      strictures in two patients, biliary strictures of the hepatic duct bifurcation in
      three patients and biliary strictures of the donor common hepatic duct in three
      patients. CONCLUSIONS: There was a trend toward increasing incidence of total
      biliary complications in recipients of DCD liver allografts compared with those
      receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was
      significantly higher. Focal ischemic type biliary strictures can be treated
      effectively in DCD liver transplant recipients with favourable results. Diffuse
      ischemic type biliary strictures in DCD liver transplant recipients ultimately
      requires retransplantation.

PMID- 22993732
TI  - Rate of serious complications of colonoscopy in Quebec.
AB  - BACKGROUND: The rate of serious complications is one marker of the quality of
      colonoscopy services. OBJECTIVE: To estimate the rate of serious complications of
      colonoscopy according to colonoscopy indication and polypectomy status. METHODS:
      A prospective cohort study of patients scheduled for colonoscopy who were
      recruited from seven endoscopy facilities across Montreal (Quebec) was conducted.
      Before colonoscopy, patients completed a brief questionnaire and provided their
      health insurance numbers. Colonoscopy indication was based on patient-reported
      medical history. Polypectomy status was obtained from provincial physician
      billing records (Regie de l'assurance maladie du Quebec). Diagnoses and
      procedures associated with hospitalization in the 30 days following colonoscopy
      were obtained from the provincial hospitalization database (MedEcho). RESULTS: Of
      the 2134 patients enrolled (mean age 60.9 years, 50.1% male), 33 (1.55% [95% CI
      1.06% to 2.16%]) were hospitalized within 30 days. One patient experienced
      bleeding following a colonoscopy that involved polypectomy and was diagnosed with
      carcinoma in situ of the rectum. Based on self-reported rectal bleeding in the
      previous six months, the colonoscopy was nonscreening. The provincial
      hospitalization data showed no occurrences of perforation, diverticulitis,
      myocardial infarction/stroke or death; thus, the rate of serious colonoscopy
      complications was 0.05% (95% CI 0.00% to 0.26%). DISCUSSION: The rate of serious
      colonoscopy complications requiring hospitalization was low and comparable with
      what is reported in the literature. The serious complication occurred subsequent
      to polypectomy and in a nonscreening colonoscopy. CONCLUSION: The findings
      support the relative safety of screening colonoscopy in persons without large
      bowel diseases and symptoms. However, future research to determine the rate of
      serious complications not requiring hospitalization is warranted to reassure
      decision makers of the safety of colonoscopy for colorectal cancer screening.

PMID- 22993733
TI  - Autoimmune hepatitis: focusing on treatments other than steroids.
AB  - BACKGROUND: Corticosteroid therapy has been the time-honoured treatment for
      autoimmune hepatitis; however, the emergence of new immunosuppressive agents has
      afforded opportunities to improve or replace the standard regimens. OBJECTIVE: To
      describe technological advances and feasible treatment interventions that promise
      to supplant the current generation of corticosteroids. METHODS: A review of the
      MEDLINE database for published experiences from 1984 to 2011 was conducted.
      RESULTS: Cyclosporine and tacrolimus have been uniformly successful as salvage
      therapies for steroid-refractory autoimmune hepatitis. Ten reports of
      cyclosporine therapy involving 133 patients had positive outcomes in 93%, whereas
      therapy with tacrolimus in three reports involving 41 patients had positive
      outcomes in 98%. Salvage therapy with mycophenolate mofetil had a favourable
      outcome in 47%, especially in patients with azathioprine intolerance. Front-line
      therapy with mycophenolate mofetil normalized liver parameters in 88% and allowed
      corticosteroid tapering in 58%. Front-line therapy with budesonide combined with
      azathioprine for six months normalized liver parameters more frequently (47%
      versus 18%) and with fewer side effects (28% versus 53%) than prednisone combined
      with azathioprine. Monoclonal antibodies to CD3 and recombinant cytotoxic T
      lymphocyte antigen 4 fused with immunoglobulin represent feasible molecular
      interventions for study in autoimmune hepatitis. DISCUSSION: Nonstandard drug
      therapies must be used in highly selected clinical situations including steroid
      failure (calcineurin inhibitors), azathioprine intolerance (mycophenolate
      mofetil), and mild disease or fragile patients (budesonide combined with
      azathioprine). Molecular interventions for autoimmune hepatitis are feasible for
      study because of their use in other immune-mediated diseases. CONCLUSION:
      Opportunities to improve or replace standard corticosteroid regimens have
      emerged.

PMID- 22993734
TI  - Pregnancy following liver transplantation: review of outcomes and recommendations
      for management.
AB  - Liver transplantation is considered to be the treatment of choice for end-stage
      liver disease and its success has led to an increase in the number of female
      liver transplant recipients who are of childbearing age. Several key issues that
      are noted when counselling patients who are considering pregnancy following liver
      transplantation include the optimal timing of pregnancy, optimal contraception
      methods and the management of immunosuppression during pregnancy. The present
      review summarizes the most recent literature so that the clinician may address
      these issues with their patient and enable them to make informed decisions about
      pregnancy planning. The authors review recent studies examining maternal and
      fetal outcomes, and the rates of complications including risk of graft rejection.
      Subsequently, the authors provide recommendations for counselling prospective
      mothers and the management of the pregnant liver transplant recipient.

PMID- 22993735
TI  - Long-term natural history and complications of collagenous colitis.
AB  - Microscopic forms of colitis have been described, including collagenous colitis,
      a possibly heterogeneous disorder. Collagenous colitis most often appears to have
      an entirely benign clinical course that usually responds to limited treatment.
      Sometimes significant extracolonic disorders, especially arthritis, spondylitis,
      thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the
      clinical course and influence the treatment strategy. However, rare fatalities
      have been reported and several complications, some severe, have been attributed
      directly to the colitis. Toxic colitis and toxic megacolon may develop.
      Concomitant gastric and small intestinal inflammatory disorders have been
      described including celiac disease and more extensive collagenous inflammatory
      disease. Colonic ulceration has been associated with the use of nonsteroidal anti
      inflammatory drugs, while other forms of inflammatory bowel disease, including
      ulcerative colitis and Crohn disease, may evolve directly from collagenous
      colitis. Submucosal 'dissection', colonic fractures, or mucosal tears and
      perforation, possibly from air insufflation during colonoscopy, have been
      reported. Similar changes may result from increased intraluminal pressures that
      may occur during radiological imaging of the colon. Neoplastic disorders of the
      colon may also occur during the course of collagenous colitis, including colon
      carcinoma and neuroendocrine tumours (ie, carcinoids). Finally,
      lymphoproliferative disease has been reported.

PMID- 22993737
TI  - Module 2: Rethinking the role of thiazide-type diuretics in the management of
      hypertension: which diuretic is best?

PMID- 22993736
TI  - The impact of farnesoid X receptor activation on intestinal permeability in
      inflammatory bowel disease.
AB  - The most important function of the intestinal mucosa is to form a barrier that
      separates luminal contents from the intestine. Defects in the intestinal
      epithelial barrier have been observed in several intestinal disorders such as
      inflammatory bowel disease (IBD). Recent studies have identified a number of
      factors that contribute to development of IBD including environmental triggers,
      genetic factors, immunoregulatory defects and microbial exposure. The current
      review focuses on the influence of the farnesoid X receptor (FXR) on the
      inhibition of intestinal inflammation in patients with IBD. The development and
      investigation of FXR agonists provide strong support for the regulatory role of
      FXR in mucosal innate immunity. Activation of FXR in the intestinal tract
      decreases the production of proinflammatory cytokines such as interleukin (IL) 1
      beta, IL-2, IL-6, tumour necrosis factor-alpha and interferon-gamma, thus
      contributing to a reduction in inflammation and epithelial permeability. In
      addition, intestinal FXR activation induces the transcription of multiple genes
      involved in enteroprotection and the prevention of bacterial translocation in the
      intestinal tract. These data suggest that FXR agonists are potential candidates
      for exploration as a novel therapeutic strategy for IBD in humans.

PMID- 22993738
TI  - Module 3: Using thiazide-type diuretics in African Americans with hypertension.

PMID- 22993739
TI  - Module 4: Enhancing adherence with antihypertensives: the role of fixed-dose
      combinations and home blood pressure monitoring.

PMID- 22993740
TI  - Module 1: Historical review of evidence-based treatment of hypertension.

PMID- 22993741
TI  - Application of age-adjusted D-dimer threshold for exclusion thromboembolism (PTE)
      in older patients: a retrospective study.
AB  - BACKGROUND: The D-dimer assay's ability to exclude pulmonary thromboembolism
      (PTE) falls with age.1,2 Douma et al. have proposed an age-adjusted D-dimer
      threshold ([threshold, ug/l] = [age, years] x 10) for patients aged >50 years
      with low clinical risk of PTE.3 We retrospectively applied this threshold to
      patients who underwent computer tomographic pulmonary angiogram (CTPA) for
      suspected PTE during a 13 month period at a busy District General Hospital. Of
      the 423 patients >50 years old who underwent CTPA, 22 (5.2%) had D-dimer
      concentrations higher than the traditional threshold but lower than the age
      adjust threshold, none of whom had evidence of PTE on CTPA. This suggests that
      use of the age-adjusted D-dimer threshold may reduce necessity for CTPA concept
      patients aged >50 years.

PMID- 22993742
TI  - Food for thought in an doctors' knowledge of herbal medicines needs to be better.
AB  - INTRODUCTION: Patients are increasingly taking herbal supplements for a variety
      of reasons. This has brought into question doctors knowledge about herbal
      medicines. METHOD: A cross-sectional web-based survey of 84 doctors working
      within the Department of Medicine at a District General Hospital was carried out
      looking at doctor's knowledge about herbal medicines. RESULTS: 53 doctors took
      part. Of these, the majority were trainees in Medicine (42) 79%. Only (15) 28%
      routinely ask patients about herbal medicine use when taking a drug history.
      Doctor's knowledge about herbal Medicines was poor. CONCLUSION: We need to re
      examine our current teaching programmes to ensure that education about common
      herbal medicines and important sources of information are provided to doctors to
      improve patient safety.

PMID- 22993743
TI  - The management of venous thromboembolic diseases and the role of thrombophilia
      testing: summary of NICE Guideline CG144.
AB  - Venous thromboembolic disease (VTE) is a common presentation in acute medicine
      and ensuring fast, accurate diagnosis and appropriate management is important.
      Getting it right not only reduces mortality but can also reduce the long-term
      complications associated with the disease such as post-thrombotic syndrome (PTS)
      and chronic thromboembolic pulmonary hypertension.

PMID- 22993744
TI  - Presentations to an acute medical unit due to headache: a review of 306
      consecutive cases.
AB  - The United Kingdom National Health Service has recently prioritised the need for
      ambulatory care pathways for acute headache. The present study sought to better
      characterise patients referred to an Acute Medical Unit so as to inform pathway
      development. In 2011, York Hospital received 306 referrals due to acute headache,
      representing 3% of acute medical admissions. Investigations included CT scan
      (38%), lumbar puncture (38%), and MRI (18%); there were no specialised
      investigations in 26%, and 18% of patients were discharged on the day of
      presentation. Subarachnoid haemorrhage occurred in only 4 patients (1%),
      meningitis in 10 (3%), and intracranial tumour in 5 (2%). The findings indicate
      that a significant proportion of patients with acute headache could be managed by
      ambulatory care.

PMID- 22993745
TI  - An unusual cause of confusion and hyponatraemia in an elderly patient.
AB  - A large proportion of patients presenting on the acute medical take are frail and
      elderly and a significant proportion of these will have symptoms such as
      confusion, reduced mobility and electrolyte disturbances. These symptoms are
      typically attributed either to the iatrogenic effects of prescribed medications,
      disturbances in fluid balance and possible infective causes. We describe the case
      of a gentleman who presented with delirium, reduced mobility and hyponatraemia
      who was subsequently found to have pituitary failure secondary to pituitary
      apoplexy.

PMID- 22993746
TI  - Enough to bring a lump to the throat: two emergency presentations to the acute
      medical take.
AB  - An eighty nine year old woman was admitted with a two day history of abdominal
      pain and vomiting. Two months previously she had undergone a Hartmann's procedure
      following a sigmoid perforation secondary to diverticular disease. A hiatus
      hernia had been noted on a CT undertaken prior to her recent surgery.

PMID- 22993747
TI  - Out with the old, in with the new? Case reports of the clinical features and
      acute management of two novel designer drugs.
AB  - Methoxydine (4-MeO-PCP) and Methoxetamine (3-MeO-2-Oxo-PCE) are both commercially
      produced designer drugs with structural and biochemical similarities to
      phencyclidine (PCP). Although phencyclidine toxicity is well documented, its
      recreational use in present times is rare. With the advent of new designer drugs
      being available widely through internet sites, Acute Physicians should be aware
      of the clinical features and management of these potential toxins. We present a
      case of methoxydine ingestion (which to our knowledge has not been previously
      documented in any medical journals) and a case of methoxetamine ingestion, and
      discuss their history, contrasting clinical features and acute management.

PMID- 22993748
TI  - Clinically lean; "cutting the crap".
AB  - Proponents of Lean Philosophy believe that successful businesses must reduce
      waste in working time and resources to a minimum, and maximise their use in
      productive work. The productive work of the Acute Medical Unit is to provide
      effective clinical management to a daily cohort of acutely ill patients. Many
      Clinicians are cynical about Lean. In this article, Dr Caldwell discusses how
      many clinicians complain of too much crap in the workplace, which gets in the way
      of swift, safe high quality clinical care. He argues that "Cutting the Crap" in
      the Acute Medical Unit is entirely consistent with Lean approaches to management
      of complex systems.

PMID- 22993750
TI  - Problem based review: the patient with 'palpitations'.
AB  - Palpitations, or the sensation of a rapid or heavy heartbeat, are a common
      symptom in both primary and secondary care settings. Here we use a common
      presentation of palpitations to explore the best ways to assess and treat
      patients who present in this way. We hope that by using a structured approach to
      our assessment we will reduce the use of the 'scattergun' approach to diagnosis,
      thus preventing unnecessary investigation and hospital stay.

PMID- 22993751
TI  - Problem based review: pleuritic chest pain.
AB  - Pleuritic pain, a sharp discomfort near the chest wall exacerbated by inspiration
      is associated with a number of pathologies. Pulmonary embolus and infection are
      two common causes but diagnosis can often be challenging, both for experienced
      physicians and trainees. The underlying anatomy and pathophysiology of such pain
      and the most common aetiologies are presented. Clinical symptoms and signs that
      may arise alongside pleuritic pain are then discussed, followed by an
      introduction to the diagnostic tools such as the Wells? score and current
      guidelines that can help to select the most appropriate investigation(s).
      Management of pulmonary embolism and other common causes of pleuritic pain are
      also discussed and highlighted by a clinical vignette.

PMID- 22993752
TI  - Rapid and direct detection of attomole adenosine triphosphate (ATP) by MALDI-MS
      using rutile titania chips.
AB  - We report the rutile titania-based capture of ATP and its application as a MALDI
      MS target plate. This chip, when immersed in solutions containing different
      concentrations of ATP, can capture ATP and lead to its successful detection in
      MALDI-MS. We have optimized the ideal surface, showing an increased capture
      efficacy of the 900  degrees C (rutile) titania surfaces. We demonstrate the use
      of this chip as a target plate for direct analysis of the attached ATP using
      MALDI-MS, down to attomolar concentrations. This chip has a promising future for
      the detection of ATP in environmental samples, which may eventually be used as a
      pollution indicator in particular environments.

PMID- 22993753
TI  - Practical evaluation of late-night salivary cortisol: a real-life approach.

PMID- 22993754
TI  - [A study on the infection level of H5N1 virus in the birds- exposure population
      in Changsha].

PMID- 22993755
TI  - [Coinfection by Borrelia burgdorferi, Francisella tularensis and Coxiella
      burnetii in domestic animals from Gansu province, China].

PMID- 22993756
TI  - [Two different clones of Escherichia coli successively isolated from two samples
      from urine of an inpatient].

PMID- 22993757
TI  - [The association between socio-economic status and elderly instrumental
      activities of daily life in China].

PMID- 22993758
TI  - [Reasons and influencing factors of  patient-loss in methadone maintenance
      treatment clinics in Wuxi].

PMID- 22993759
TI  - [Analysis of urinary iodine levels in patients with thyroid diseases in Yuhuan
      county].

PMID- 22993760
TI  - [A case of horsehair worms parasitized in vagina accidentally].

PMID- 22993762
TI  - Ralf J Jox.

PMID- 22993763
TI  - Brains: the mind as matter.

PMID- 22993761
TI  - [Epidemiology of travel-associated influenza A (H1N1) 2009 infection in Beijing].

PMID- 22993764
TI  - [Observation on the effect of population-based immunization of influenza A
      (H1N1)2009 split-virus vaccine].

PMID- 22993765
TI  - [Factors associated with immunization of novel influenza A (H1N1) vaccine in
      Beijing, 2009].

PMID- 22993766
TI  - [Immunogenicity for different formulation of influenza A (H1N1) 2009 vaccines: a
      meta-analysis of seven randomized clinical trials].

PMID- 22993767
TI  - [The evaluation on the impact of "Wenchuan Earthquake" on maternal and children
      health information-collecting capacity of countryside in the quake-hit counties].

PMID- 22993768
TI  - [Acute demyelination of central nervous system after influenza A
      (H1N1)infectious].

PMID- 22993769
TI  - [Relationship between blood pressure at admission and clinical outcome during
      hospitalization among patients with intracerebral hemorrhage].

PMID- 22993770
TI  - [Epidemiology of hepatitis E in clinical patients in Dongtai, Jiangsu province].

PMID- 22993771
TI  - [SNaPshot detect association of genetic polymorphisms in transforming growth
      factor Beta-1 with hypertension in the Kazakh ethnicities of Xinjiang].

PMID- 22993772
TI  - [Analysis on the potential loss of maternal mortality in Gannan Tibetan
      Autonomous Prefecture, China].

PMID- 22993773
TI  - [Male circumcision in reducing HIV infection risk in men: a meta-analysis study].

PMID- 22993774
TI  - [A study on the general health conditions in resident of Beichun six months after
      the Wenchuan earthquake].

PMID- 22993775
TI  - [Association between social factors and blood pressure level in both males and
      females].

PMID- 22993776
TI  - [An epidemiological study on the sleep disorders of pregnant women in Wenshou,
      Zhejiang province].

PMID- 22993777
TI  - [A prevalence survey on the incidence of genital warts between urban and rural
      areas in China].

PMID- 22993778
TI  - [Application of principal component analysis to construct socio-economic status
      index in a case-control study].

PMID- 22993779
TI  - [Study on the prevalence of metabolic syndrome among the elderly population aged
      60 and over in Bazhong, Sichuan province].

PMID- 22993780
TI  - [Study on the influence factors of nutrition status of children under 3-year-old
      in rural areas of the Midwestern provinces in China].

PMID- 22993781
TI  - [District difference in development and the prevalence of obesity among 7-18
      years old children and adolescents in Shandong, China].

PMID- 22993782
TI  - [Study on HIV and syphilis infections and related risk behaviors among male sex
      workers in Beijing, China].

PMID- 22993783
TI  - [Molecular epidemiology regarding Anaplasma phagocytophilum in Dermacentor
      silvarum in Ningwu county, Shanxi province].

PMID- 22993784
TI  - [DNA detection and sequence analysis of Borrelia burgdorferi sensu lato in
      rodents from Helongjiang and forest region].

PMID- 22993785
TI  - [Short-term effects of weather on the incidence of hand, foot and mouth disease
      in Guangzhou city].

PMID- 22993786
TI  - [Isolation and characterization of Leclercia adecarboxylata strains from feces of
      disease of diarrhea patients].

PMID- 22993787
TI  - [Epidemiologic study on HIV-1 gene subtypes in different groups of HIV-1
      infectors in Liaoning province, 2008-2010].

PMID- 22993788
TI  - [Serological survey on antibody to H9 subtypes of avian influenza A virus in
      medical college students in Guangxi of China and Hue of Vietnam].

PMID- 22993789
TI  - [Epidemiology of hepatitis E in Fujian province, 2004-2010].

PMID- 22993790
TI  - [Behavior among young males having multiple sexual partner involved in unmarried
      abortions and its contributing factors].

PMID- 22993791
TI  - Acute myeloid leukemia with Charcot-Leyden crystals.

PMID- 22993792
TI  - [Effectiveness and safety of preventive usage of liver protective drugs during
      anti-tuberculosis therapy: a systematic review of clinical trials in China].

PMID- 22993793
TI  - [Retrospective epidemiologic investigation on congenital rubella syndrome in
      monitoring region of Shandong province, China].

PMID- 22993794
TI  - [Sequencing and phylogenetic analysis for non-structure protein coding region of
      dengue virus from Yunnan border].

PMID- 22993795
TI  - [An investigation of eperythrozoon infection in a village Liaoning province].

PMID- 22993796
TI  - [Analysis on dynamic monitoring of chronic diseases and their risk factors in
      Changping district, Beijing].

PMID- 22993797
TI  - [Direct and indirect economic burden of 999 cystic echinococcosis patients in
      tertiary hospital].

PMID- 22993798
TI  - [Analysis on the status of iodine deficiency disorders in the high risk area of
      Gansu province].

PMID- 22993799
TI  - [A retrospective study on an incident, regarding hepatitis C virus infection in
      groups caused by unlawful blood collection and supply].

PMID- 22993800
TI  - [Investigation on the risk factors in first-degree relatives with normal glucose
      tolerant of type 2 diabetics' patients in Chanzhi, Shanxi].

PMID- 22993801
TI  - [A study on the epidemic and etiologic characteristics of Shigella B and D group
      in Henan province].

PMID- 22993802
TI  - [Study on genotypes and geographical distribution of 58 strains of Yersinia
      pestis in Gansu].

PMID- 22993803
TI  - [Analysis on data from influenza surveillance of Zhuzhou city, 2005-2008].

PMID- 22993804
TI  - [Necessity of and the reasons for refusal on medical staff regarding injection of
      influenza vaccine and A (H1N1)].

PMID- 22993805
TI  - [Differences on sexual characteristic between HIV-positive men who know their HIV
      status and HIV-positive men who are unaware of their HIV status among men who
      have sex with men in China].

PMID- 22993806
TI  - [Research on behavior characteristics of men who have sex with men with 50-plus
      years].

PMID- 22993807
TI  - [Research on family function of people living with HIV/AIDS and its influence in
      Henan province].

PMID- 22993808
TI  - [Analysis on immune status and virus load of 1969 newly reported HIV/AIDS cases
      in Henan province, 2009].

PMID- 22993809
TI  - [Analysis on AIDS related knowledge, risk behavior, health needs and utilization
      of health service through sentinel surveillance among drug users in Gansu
      province from 2006 to 2009].

PMID- 22993810
TI  - [Awareness of knowledge, attitude and practice on expanded program on
      immunization of grass-root doctors in western areas of China].

PMID- 22993811
TI  - [Analysis for VP4, VP6, NSP4, and NSP5 genes of human rotavirus G9 identified fro
      2007-2008, in Beijing].

PMID- 22993812
TI  - [Investigation on epidemic status of echinococcosis in pastoral villages of
      Chengduo county, Qinghai].

PMID- 22993813
TI  - [Survey on the service demands from the elderly in Nantong, Jiangsu].

PMID- 22993814
TI  - [Influenza vaccination coverage rates and factors associated with vaccine use
      among the elderly in Beijing during 2008-2010].

PMID- 22993815
TI  - [Hypertension survey in Youyu county of Shanxi province].

PMID- 22993816
TI  - [Quality of life among the elderly hypertensive population in two areas of
      Zhejiang province].

PMID- 22993817
TI  - [A study on the relationship between family environment and anxiety of the
      undergraduates in medical universities].

PMID- 22993819
TI  - [Study on the authenticity of immunization coverage on the routine immunization
      coverage surveillance system of Fujian province].

PMID- 22993818
TI  - [Intention survey of target population with regard to H1N1 influenza
      vaccination].

PMID- 22993820
TI  - [An outbreak of dermatitis caused by Pyemotes ventricosus parasitic in
      tristletail in a kindergarten].

PMID- 22993821
TI  - [Serological survey on viral hepatitis B in the population of Shanxi province].

PMID- 22993822
TI  - [Phylogenetic analysis on pandrug-resistant Acinetobacter baumannii strains].

PMID- 22993823
TI  - [Epidemiological analysis of rubella in Beijing 100013, China].

PMID- 22993824
TI  - [Non-and-low response after hepatitis B vaccine of 1085 infants in Ningbo and
      analysis on its influential factors].

PMID- 22993825
TI  - [A cross-sectional study on the cases of hepatitis B reported in Wuhan, Hubei
      province in 2010].

PMID- 22993826
TI  - [Analysis on the epidemiological characteristics of hand-foot-mouth disease in
      Xuchang, Henan province in 2010].

PMID- 22993827
TI  - [Situation of consultation-need and the practice on sexually transmitted
      infections prevention and treatment among unmarried youth in China].

PMID- 22993828
TI  - Go back, Jack, and do it again: the underrated art of replication.

PMID- 22993829
TI  - CMS head CT rule under fire.

PMID- 22993830
TI  - The gold standard's flexible alloy: adaptive designs on the advance.

PMID- 22993831
TI  - [A retrospective sero-epidemiology study of poliomyelitis antibody level in the
      population of recruits].

PMID- 22993832
TI  - [Analysis on epidemiologic characteristics of infectious diarrhea in Xianju,
      Zhejiang province during 2004 and 2007].

PMID- 22993834
TI  - [Epidemiological analysis of early cases of influenza A (H1N1) in Guangdong
      province, China].

PMID- 22993835
TI  - [An outbreak of novel influenza A (H1N1) in a primary school, Dongguan city,
      Guangdong province, China].

PMID- 22993836
TI  - [Detection of Ehrlichia in ticks in Suizhou city of Hubei province, China].

PMID- 22993837
TI  - [Analysis on the characteristics of 'National Safety Accident Reports', in
      China].

PMID- 22993838
TI  - [Evaluation on the family function of the elderly and its influential factors in
      rural area in Shaoxing, Zhejiang province].

PMID- 22993839
TI  - [Molecular epidemiology of noroviruses in Shenzhen in 2006].

PMID- 22993840
TI  - Analysis of the proximity of fatal motor vehicle crash locations to the
      availability of helicopter emergency medical service response.

PMID- 22993841
TI  - [Analysis on gender difference of correlative factors among drug abusers].

PMID- 22993842
TI  - [Result of serology test for yellow fever virus (YFV) in the entry-exit persons
      in Guangzhou frontier port and the forecast of risk on YFV infection].

PMID- 22993843
TI  - [Epidemiological analysis of Mycoplasma pneumoniae acute infection in adults with
      community-acquired pneumonia].

PMID- 22993844
TI  - [Research progress and trend analysis of biology and chemistry of Taxus medicinal
      resources].
AB  - Taxus is the source plant of anti-cancer drug paclitaxel and its biosynthetic
      precursor, analogs and derivatives, which has been studying for decades. There
      are many endemic Taxus species in China, which have been studied in the field of
      multiple disciplines. Based on the recent studies of the researchers, this review
      comments on the study of Taxus biology and chemistry. The bibliometric method is
      used to quantify the global scientific production of Taxus-related research, and
      identify patterns and tendencies of Taxus-related articles. Gaps are present in
      knowledge about the genomics, epigenomics, transcriptomics, proteomics,
      metabolomics and bioinformatics of Taxus and their endophytic fungi. Systems
      biology and various omics technologies will play an increasingly important role
      in the coming decades.

PMID- 22993845
TI  - [Advances in the study of derivatization of ginsenosides and their anti-tumor
      structure-activity relationship].
AB  - Ginsenosides, belonging to a group of saponins with triterpenoid dammarane
      skeleton, show a variety of pharmacological effects. Among them, some ginsenoside
      derivatives, which can be produced by acidic and alkaline hydrolysis,
      biotransformation and steamed process from the major ginsenosides in ginseng
      plant, perform stronger activities than the major primeval ginsenosides on
      inhibiting growth or metastasis of tumor, inducing apoptosis and differentiation
      of tumor and reversing multidrug resistance of tumor. Therefore ginsenoside
      derivatives are promising as antitumor active compounds and drugs. In this
      review, the derivatization methods, ginsenoside derivatives and their anti-tumor
      structure-activity relationship have been summarized for providing useful
      information for the research and development of novel antitumor drugs.

PMID- 22993846
TI  - [Research progresses of plant polysaccharides on cell adhesion].
AB  - Cell adhesion mediated by cell adhesion molecules (CAMs) constitutes essential
      life phenomenon. In inflammation, immunity, infection, thrombosis, tumor
      metastasis and wound healing, cell adhesion comes into being the basic
      physiological and pathological process. Intervening with cell adhesion has been
      the important therapeutic and prophylactic strategies for diseases. Accumulated
      evidence has indicated that plant polysaccharides especially those exacted from
      Chinese traditional and herbal drugs displayed various pharmacological effects
      such as anti-inflammation, anti-cancer, anti-infection, immunomodulation,
      cardiovascular protective effects and so on. In this paper, the research progress
      of plant polysaccharides on cell adhesion is reviewed.

PMID- 22993847
TI  - [Advance in the study of targeting delivery system for siRNA mediated by
      aptamers].
AB  - RNA interference (RNAi), as a new technology of gene therapy, has been used in
      the studies of many diseases in vitro, however, targeting delivery of small
      interference RNA (siRNA) is still a bottleneck for clinical therapy of siRNA
      agents. Aptamer is a group of oligonucleotides with high affinity and targeting,
      and is becoming another important means of delivery for siRNA. In this review, we
      summarized siRNA delivery obstacles in vivo and recent attractive developments
      increatively using cell-internalizing aptamers to deliver siRNAs to target cells.

PMID- 22993848
TI  - [Methods for grain size analysis of nanomedicines].
AB  - As nanomedicines are developing fast in both academic and market areas, building
      up suitable methods for nanomedicine analysis with proper techniques is an
      important subject, requiring further research. The techniques, which could be
      employed for grain size analysis of nanomedicines, were reviewed. Several key
      techniques were discussed with their principles, scope of applications,
      advantages and defects. Their applications to nanomedine analysis were discussed
      according to the properties of different nanomedicines, with the purpose of
      providing some suggestions for the control and administration of nanomedicines.

PMID- 22993849
TI  - [Integrated pharmacokinetic study of multiple effective components of tea
      polyphenols and its correlation with anti-free radical pharmacodynamics in rats].
AB  - LC-MS/MS method was used to simultaneously determine anti-oxidative active
      catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols
      (TP). The integrated plasma concentration (C') of TP was calculated by means of
      self-defined weighing coefficient based on percent AUC of individual components,
      thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T
      curve. The anti-free radical effects of TP were estimated using inhibitory rate
      of drug-containing serum collected at different times from rats against in vitro
      lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used
      to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and
      E-log C' plots and linear regression were carried out in order to obtain the
      correlation coefficient (R2). The results indicated that the log C'-T curves of
      TP, which could be best described by three-compartment model, corresponded to
      elimination rule of iv administration of drugs. The integrated PK parameters
      showed that TP was distributed in body rapidly and widely, and eliminated from
      deep compartment slowly. From comparison of R2 values and consistence of C'-T
      course and E-T course, it was evident that TP integrated PK behaviors correlated
      much better with its PD behaviors than individual active components, and thus
      demonstrated that integrated PK parameters could characterize to maximal extent
      holistic disposition of Chinese herbal drugs and reflect residence properties of
      holistic effective substances in biological body.

PMID- 22993850
TI  - [Effect of sailuotong capsule on Glu and GABA levels as well as NMDA receptor
      subtypes expression in recovery period of rat multiple cerebral infarction].
AB  - The rat model of multi-infarct was adopted in this study to elucidate the
      protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of
      multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA
      and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were
      detected. The multi-infarct model rats were established by injecting embolizing
      microsphere via internal carotid artery, and were given Sailuotong treatment
      (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain
      ultrastructure were observed by transmission electron microscope. The levels of
      Glu and GABA in brain tissue were measured with high performance liquid
      chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in
      neurons was evaluated by immunohistochemical staining. Compared with the sham
      rats, abnormal changes were observed in ultrastructures of neurons, neuroglia
      cells and synapses of model rat brains. Moreover, significant decrease of Glu and
      GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in
      brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve
      ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down
      regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated
      that Sailuotong could exert neuroprotective effects to some extent in the
      recovery phase of multiple cerebral infarction by promoting expression of NMDA
      receptors and synthesis of Glu and GABA.

PMID- 22993851
TI  - [Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of
      tacrolimus in renal transplant patients].
AB  - The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area
      ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal
      transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal
      transplant patients were determined by PCR-RFLP method. The differences of C/D'
      ratios, adverse reactions and acute rejection were compared among all of the
      genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and
      CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively.
      No significant association was found between the C/D's of tacrolimus and
      CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P >
      0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D'
      ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was
      significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There
      is no significant difference in adverse effects and acute rejection among
      different genotypes (P > 0.05).

PMID- 22993852
TI  - [Immunoregulatory effect of artesunate on allergic contact dermatitis and its
      mechanism].
AB  - This study is to elucidate the immunoregulation mechanisms of artesunate (AST) on
      allergic contact dermatitis (ACD). Pharmacodynamics analyses, HE staining, semi
      quantitative RT-PCR and Western blotting were used to explore the effects of AST
      on the related cytokines, transcription factor and signaling molecule of ACD
      respectively. The results indicated that topical administration of AST not only
      reduced the increase of ear swelling, spleen index and inflammatory cells
      infiltration in ACD mice, but also inhibited remarkably the expression of IFN
      gamma, T-bet and NF-kappaB p65. It's suggested that AST could exhibit suppressive
      effects on inflammatory response and immune function of ACD, which indicates the
      possibility of developing AST as a novel immunoregulatory agent in the treatment
      of ACD and other immune-related diseases.

PMID- 22993853
TI  - [Comparison of effects of kaempferide and anhydroicaritin on biomineralization of
      cultured osteoblasts].
AB  - This study is to compare the effects of kaempferide and anhydroicaritin on
      biomineralization of rat osteoblasts (ROB) in vitro. Calvarias were dissected
      aseptically from newborn SD rats, the osteoblasts were obtained by enzyme
      digestion and were cultured in MEM containing 10% FBS. The medium was changed
      every three days, and serial subculture was performed when cells covered with 90%
      of the dish. Kaempferide and anhydroicaritin were separately added with final
      concentrations of 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) and 1 x 10(-7) mol x L(-1)
      under the conditions of osteogenic differentiation. The proliferation was
      measured by MTT, and the optimal concentration was detected by the ALP activity
      at the 9th day after osteogenic induction culture. The osteogenic indexes of
      kaempferide, anhydroicaritin and control group with the optimal concentration
      were compared. The result showed that the anhydroicaritin at concentration of 1 x
      10(-5) mol x L(-1) had significantly promoted the activity of ALP, calcium
      content and osteocalcin content, increased the number of CFU-F(ALP) and
      mineralized nodules, enhanced the mRNA level of BMP-2, OSX and Runx-2, which are
      key genes of osteogenic differentiation, and raised the protein content of
      collagen-I. However, the kaempferide group had not significantly represented the
      ability that promoted osteogenic differentiation of ROB. The difference of
      osteogenic differentiation on ROB between kaempferide and anhydroicaritin was
      caused by the prenyl group on C-8 of icariin.

PMID- 22993854
TI  - [Optimization and characterization of a novel FGF21 mutant].
AB  - Fibroblast growth factor 21 (FGF21) is a member of FGF family. It has been
      demonstrated that FGF21 is an independent, safe and effective regulator of blood
      glucose levels in vivo. In order to improve the activity of FGF21, we exchanged
      the beta10-beta12 domain of the human FGF21 with that of the mouse FGF21 to
      construct a novel FGF21 gene (named hmFGF21), and then subcloned hmFGF21 gene
      into the SUMO expression vector to create pSUMO-hmFGF21 and transformed it into
      E. coli Rosetta for expression of the fusion protein SUMO-hmFGF21. Both in vitro
      and in vivo glucose regulation activity of hmFGF21 was evaluated. The SDS-PAGE
      result showed that compared with wild-type hFGF21, the soluble expression of
      hmFGF21 increased about 2-fold. HmFGF21 was more potent in stimulation of glucose
      uptake in HepG2 cells in vitro. The results of anti-diabetic effect on db/db mice
      demonstrated that hmFGF21 had better efficacy on controlling the blood glucose of
      the db/db diabetic animals than wild-type hFGF21. These results suggest that the
      biological properties of FGF21 are significantly improved by optimization.

PMID- 22993855
TI  - [Effects of jin chai antiviral capsule on IFITM3 expression in mice].
AB  - This study is to investigate the treatment of Jin Chai antiviral capsule for
      influenza virus FM1/47 (H1N1) infection. The model of pneumonia was established
      by dropping influenza virus into the nose of normal mice, real-time PCR and
      Western blot technique were used to detect the virus load and the
      interferoninducible transmembrane protein3 (IFITM3) in lung of mice at the 1st
      day, 3rd day, 5th day and 7th day after affected. The results showed that Jin
      Chai antiviral capsule in large, middle, small dose groups can decrease virus
      load significantly at each time point, after being affected (P<0.05, P<0.01), Jin
      Chai antiviral capsule can increase the interferoninducible transmembrane
      protein3 in lung of mice, large dose groups are significantly higher in
      expression of IFITM3 compared with model group at each time point (P<0.05,
      P<0.01). Middle dose groups are significantly higher in expression of IFITM3
      compared with model group at the 3th day and the 5th day (P<0.05), small dose
      groups are significantly higher in expression of IFITM3 compared with model group
      at the 3th day (P<0.05). It can be concluded that Jin Chai antiviral capsule
      exerts antiviral effects against influenzavirus by raised expression of IFITM3.

PMID- 22993856
TI  - [Design and activity verification of human parathyroid hormone (1-34) mutant
      protein].
AB  - Through protein-protein BLAST of homologous sequences in different species in
      NCBI database and preliminary simulating molecular docking and molecular dynamics
      by computer software discovery studio 3.1, three amino acids R25K26K27 of natural
      human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological
      activity of the mutant peptide was evaluated. Result showed that: root mean
      superposition deviation RMSD value between PTH (1-34)-(RKK-QEL) and PTH (1-34)
      peptide main chain was 2.509 3, indicating that the differences between the two
      main chain structural conformation was relatively small; the interaction energy
      between PTH (1-34)-(RKK-QEL) and its receptor protein PTH1R had been enhanced by
      7.5% compared to nature PTH (1-34), from -554.083 kcal x mol(-1) to -599.253 kcal
      x mol(-1); the number of hydrogen bonds was increased from 32 to 38; PTH (1-34)
      (RKK-QEL) can significantly stimulate the RANKL gene expression (P < 0.01) while
      inhibiting the OPG gene expression (P < 0.01) in UAMS-32P cells; in the co
      culture system of UAMS-32P cells and mouse primary femur bone marrow cells, PTH
      (1-34)-(RKK-QEL) stimulated the formation of osteoclasts (P < 0.01) and had a
      higher biological activity than PTH (1-34) standard reagents.

PMID- 22993857
TI  - [Design, synthesis and evaluation of tacrine-methoxybenzene hybrids as
      cholinesterases inhibitors].
AB  - A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and
      evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better
      ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range.
      Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE)
      with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent
      inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic
      and molecular modeling studies showed that these hybrids targeted both the
      catalytic active site and the peripheral anionic site of AChE.

PMID- 22993858
TI  - [Chemical constituents of Trichosanthes kirilowii Maxim].
AB  - To study the chemical constituents of Trichosanthes kirilowii Maxim.,
      chromatographic methods such as D101 macroporous resin, silica gel column
      chromatographic technology, Sephadex LH-20, octadecylsilyl (ODS) column
      chromatographic technique and preparative HPLC were used and nine compounds were
      isolated from a 95% (v/v) ethanol extract of the plant. By using spectroscopic
      techniques including 1H NMR, 13C NMR, 1H-1H COSY, HSQC and HMBC, these compounds
      were identified as 5-ethoxymethyl-1-carboxyl propyl-1H-pyrrole-2-carbaldehyde
      (1), 5-hydroxymethyl-2-furfural (2), chrysoeriol (3), 4'-hydroxyscutellarin (4),
      vanillic acid (5), alpha-spinasterol (6), beta-D-glucopyranosyl-a-spinasterol
      (7), stigmast-7-en-3beta-ol (8), and adenosine (9), separately. Among them,
      compound 1 is a new compound, and compounds 3, 4 and 5 are isolated from the
      genus Trichosanthes kirilowii Maxim. for the first time.

PMID- 22993860
TI  - [Simultaneous quantitative analysis of four lignanoids in Schisandra chinensis by
      quantitative analysis of multi-components by single marker].
AB  - The aim of the study is to establish a new method of quality evaluation and
      validate its feasibilities by the simultaneous quantitative assay of four
      lignanoids in Schisandra chinensis. A new quality evaluation method, quantitative
      analysis of multi-components by single marker (QAMS), was established and
      validated with Schisandra chinensis. Four main lignanoids, schisandrin,
      schisantherin A, deoxyschizandrin and gamma-schizandrin, were selected as
      analytes and schisandrin as internal reference substance to evaluate the quality.
      Their contents in 13 different batches of samples, collected from different
      bathes, were determined by both external standard method and QAMS. The method was
      evaluated by comparison of the quantitative results between external standard
      method and QAMS. No significant differences were found in the quantitative
      results of four lignanoids in 13 batches of S. chinensis determined by external
      standard method and QAMS. QAMS is feasible for determination of four lignanoids
      simultaneously when some authentic standard substances were unavailable, and the
      developed method can be used for quality control of S. chinensis.

PMID- 22993859
TI  - [Phenolic acid derivatives from Alchornea trewioides].
AB  - To study the chemical constituents of Alchornea trewioides, silica gel column
      chromatography, Sephadex LH-20, reverse phase ODS column chromatography, MCI and
      semi-preparative HPLC were used to separate the 95% EtOH extract of the root of
      Alchornea trewioides. The structures were elucidated on the basis of
      spectroscopic studies including ESI-TOF-MS, 1H NMR, 13C NMR, HSQC and HMBC. Eight
      phenolic acids were obtained and identified as 1-O-galloyl-6-O-vanilloyl-beta
      glucose (1), gallic acid (2), ethyl gallate (3), syringic acid (4), glucosyringic
      acid (5), erigeside C (6), 3, 4-dimethoxyphenyl-(6'-O-alpha-L-rhamnosyl)-beta-D
      glucopyranoside (7) and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D
      glucopyranoside (8). Among them, compound 1 is a new compound, compounds 4-8 are
      isolated from the genus Alchornea for the first time, and the others are isolated
      from the plant for the first time.

PMID- 22993861
TI  - [Microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153].
AB  - The microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153
      was studied, as well as a microbial model which can be used to mimic metabolism
      of buflomedil in mammal was established. Experiments were conducted to screen the
      capabilities of four strains of Cunninghamella species to transform buflomedil,
      in which C. blakesleana AS 3.153 was selected for a preparative
      biotransformation. Furthermore, the microbial model was established based on the
      transformation condition optimization. The parent drug and its metabolites
      produced by C. blakesleana AS 3.153 were detected by liquid chromatography-mass
      spectrometry method and three metabolites were identified while two of them were
      new found metabolites. Two major metabolites, para-O-desmethyl buflomedil and 12
      C-oxidated buflomedil, were isolated by semi-preparative HPLC. Based on the
      comparison between different species, the microbial transformation of buflomedil
      by C. blakesleana AS 3.153 is more similar to the metabolism of buflomedil in
      human and Beagle dog than that in rat.

PMID- 22993862
TI  - [Modeling and simulation activities to design sampling scheme for population
      pharmacokinetic study on amlodipine].
AB  - Reasonable sampling scheme is the important basis for establishing reliable
      population pharmacokinetic model. It is an effective method for estimation of
      population pharmacokinetic parameters with sparse data to perform population
      pharmacokinetic analysis using the nonlinear mixed-effects models. We designed
      the sampling scheme for amlodipine based on D-optimal sampling strategy and
      Bayesian estimation method. First, optimized sample scenarios were designed using
      WinPOPT software according to the aim, dosage regimen and visit schedule of the
      clinical study protocol, and the amlodipine population model reported by Rohatagi
      et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample
      scenario via Monte Carlo simulation. Third, the estimation of amlodipine
      pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on
      the simulation results. All modeling and simulation exercises were conducted with
      NONMEM version 7.2. Finally, the accuracy and precision of the estimated
      parameters were evaluated using the mean prediction error (MPE) and the mean
      absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have
      good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3,
      respectively. MAPE is 0.7% for both schemes. There is no significant difference
      in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final
      sample scenario because it has good accuracy and precision and less sample
      points. This research aims to provide scientific and effective sampling scheme
      for population pharmacokinetic (PK) study of amlodipine in patients with renal
      impairment and hypertension, provide a scientific method for an optimum design in
      clinical population PK/PD (pharmacodynamics) research.

PMID- 22993863
TI  - [An oligopeptide improves solubility of paclitaxel by non-covalent interaction].
AB  - Based on the principle of non-covalent interactions between oligopeptides and
      paclitaxel for improving the solubility of paclitaxel, an oligopeptide, N
      terminal-W(L)-FFGREKD-C terminal (W8), was designed and the solubilization effect
      of W8 on paclitaxel was detected through experiments. The binding efficiency and
      the possible optimal conformation were optimized by molecular docking program.
      The solubilization effect of W8 on paclitaxel was determined by RP-HPLC. And the
      solubilization mechanism of oligopeptide to paclitaxel was proposed at molecular
      level. It was indicated from the docking result that there existed pi-pi
      interactions and several hydrogen-bond interactions between the oligopeptide and
      paclitaxel. After being solubilized by the oligopeptide, the aqueous solubility
      of paclitaxel was increased to 28 times. This study provided basis for further
      research of the solubilization of paclitaxel by oligopeptide and confirmed a
      novel approach for the design of safe oligopeptide solubilizing excipient.

PMID- 22993864
TI  - [Cloning and expression analysis of leucoanthocyanidin reductase gene in
      Fagopyrum dibotrys].
AB  - The leucoanthocyantin reducase (LAR) gene, an important functional gene of
      catechins biosynthesis pathway, was cloned from Fagopyrum dibotrys (D.Don) Hara
      by degenerate PCR and rapid amplification of cDNA ends (RACE). The full-length
      cDNA of FdLAR is 1 581 bp (GenBank accession: JN793953), containing a 1 176 bp
      ORF encoding a 391 amino acids protein, and its 3'-untranslated region has an
      obvious polyadenylation signal. The recombinant plasmid containing FdLAR
      completed ORF was transformed into E. coli BL21 (DE3). The target fusion peptide
      with molecular weight of 66 kD was expressed under the condition of 16 degrees C
      and induced by IPTG at final concentration of 1.0 mmol x L(-1). Bioinformation
      analysis indicated that the amino acid sequence of FdLAR showed great homology to
      other LAR with the NADB-Rossmann conversed domain in the N-terminus. Real-time
      quantitative PCR was used to detect the expression levels of FdLAR gene during
      different development periods. The determination of flavonoids contents in
      appropriate rhizomes showed that the relationship between FdLAR gene expression
      and the accumulation of flavonoids displayed different trends during vegetative
      growth and reproductive growth stages, suggesting that the FdLAR gene may be
      involved in the pathway of flavonoid metabolisms in Fagopyrum dibotrys.

PMID- 22993865
TI  - [Effect of ceramide on GSTA1 in Caco-2 cells].
AB  - This study is to investigate the effects of ceramide on GSTA1 expression in Caco
      2 cells. After being exposed to ceramide for a fixed time, GSTA1 protein
      expression was detected by Western blotting analysis; GSTA1 mRNA expression was
      detected by real time PCR; dual luciferase assay was used to analyze GSTA1
      transcriptional activity and GSTA1 activity was determined toward androstanedione
      (AD) as substrate. The data showed that ceramide can significantly induce the
      expression of protein and GSTA1 mRNA, and increase transcriptional activity and
      enzyme activity of GSTA1. The results demonstrated that ceramide may increase
      resistance to chemotherapeutics in Caco-2 cells by up-regulating the expression
      of GSTA1.

PMID- 22993866
TI  - [Determination methods for the content of methyl salicylate-2-O-beta-D
      galactopyranoside (1-4)-beta-D-glucopyranoside].
AB  - The paper is to report the establishment of three methods for determination of
      methyl salicylate-2-O-beta-D-galactopyranoside (1-4)-beta-D-glucopyranoside (MSG)
      by HPLC, UV or potentiometric titration. The results determined by the three
      methods turned out to be of no significant difference (P>0.05). The method was
      chosen according to MSG difference test demands.

PMID- 22993877
TI  - High-tech heart tests and procedures you may not need--and why. Having diagnostic
      tests for your heart 'just in case' may not help you live longer or feel better,
      and might cause harm.

PMID- 22993878
TI  - On call. How do "cholesterol-lowering" cereals like oatmeal reduce LDL
      cholesterol? How much do I need to eat to make a difference?

PMID- 22993879
TI  - On call.  I have suffered with bleeding hemorrhoids for many years.  Changing my
      diet, adding fiber, and having sitz baths have not improved the problem.  My
      doctor has suggested surgery.  Is this risky?

PMID- 22993880
TI  - New options for treating sleep apnea. Now there are more comfortable ways to
      correct the disordered breathing that disrupts your slumber.

PMID- 22993881
TI  - Self help for sore muscles.  Regular exercise is vital for health and longevity,
      but often brings strains and sprains.  Here are some tips on how to ease the
      pain.

PMID- 22993882
TI  - Attractive shedding.

PMID- 22993883
TI  - [Charite Universitatsmedizin, Berlin--Campus Virchow Klinikum].

PMID- 22993884
TI  - Pumping iron in the brain.

PMID- 22993885
TI  - Kartogenin: a game-changer in regenerative medicine.

PMID- 22993886
TI  - Generation of functional hair follicles from follicle germs in a nude mouse model
      of organ replacement regenerative therapy.

PMID- 22993887
TI  - [Vasodilation regulated by H2O2].

PMID- 22993888
TI  - [Role of aquaporin, water channel in the brain].

PMID- 22993889
TI  - [A study of adverse drug reactions in the treatment of pulmonary Mycobacterium
      avium complex disease].
AB  - OBJECTIVES: Adverse drug reactions interfere with the standard treatment of
      pulmonary Mycobacterium avium complex (MAC) disease; however, few studies have
      investigated this issue. We studied adverse drug reactions in the treatment of
      pulmonary MAC disease. SUBJECTS: We retrospectively examined 74 patients who
      underwent treatment for pulmonary MAC disease in our hospital between January
      2001 and December 2009. These patients had received treatment with rifampicin,
      ethambutol (EB), and clarithromycin. We analyzed the adverse drug reactions seen
      in these patients. RESULTS: Twenty-two patients developed one or more adverse
      drug reactions that led to treatment discontinuation or change in medication,
      whereas 52 patients did not experience any adverse reactions. The incidence rate
      of adverse reactions was 29.7%. The adverse drug reactions included visual
      impairment in 9 patients, liver function disorder in 2, skin eruption in 5, and
      fever in 5. In most of the cases, the standard treatment could not be continued.
      DISCUSSION: Visual impairment associated with EB was the most common adverse drug
      reaction, and it led to the discontinuation of EB, and thus the standard
      treatment. Additionally, in case of other adverse drug reactions, it was
      difficult to find appropriate replacements for the causative drugs. Further
      investigations are required to establish a standard policy for the management of
      adverse drug reactions that can lead to the discontinuation of chemotherapy.

PMID- 22993890
TI  - [Identification of novel variable number tandem repeat (VNTR) loci in
      Mycobacterium avium and development of an effective means of VNTR typing].
AB  - INTRODUCTION: To make more effective use of variable number tandem repeat (VNTR)
      typing, we identified novel VNTR loci in Mycobacterium avium and used them for
      modified M. avium tandem repeat-VNTR (MATR-VNTR) typing. METHOD: Analysis of a
      DNA sample extracted from a clinical isolate (strain HN135) with the FLX system
      genome sequencer (Roche Diagnostic System) led to discovery of several novel VNTR
      loci. The allelic diversity of the novel VNTR loci was evaluated for 71 clinical
      isolates and compared with the diversity of the MATR-VNTR loci. To improve
      efficacy of MATR-VNTR typing, we tested typing using 2 sets of loci selected from
      the newly identified loci and the MATR loci, i.e., one set containing 7 and
      another 16 loci. Hunter Gaston's discriminatory index (HGDI) was calculated for
      these sets. RESULTS: Six VNTR loci were newly identified, of which 5 showed a
      high diversity. The HGDI was 0.980 for the improved new typing using a set of 7
      loci, and 0.995 for another set of 16 loci, while it was 0.992 for the
      conventional MATR-VNTR typing. DISCUSSION: VNTR typing with the set of the 7 loci
      enabled a rapid analysis, and another set of 16 loci enabled a precise analysis,
      as compared with conventional MATR-VNTR typing. A method that uses only VNTR loci
      with relatively high allelic diversity is considered to be a useful tool for VNTR
      typing of MAC isolates.

PMID- 22993891
TI  - [A case of pulmonary tuberculosis associated with orbital myositis].
AB  - Ocular tuberculosis is rare. We report a case of orbital myositis suspected to be
      infected with tuberculosis. In January 2008, a 34-year-old man experienced
      discomfort in the right eye. In May 2008, this patient developed right
      exophthalmos, diplopia, and pain in the right eye, and he was diagnosed with
      idiopathic orbital myositis. The patient underwent 2 courses of steroid pulse
      therapy; after which, the dosage of steroids was reduced. The steroid treatment
      reduced the eye pain, but his diplopia and exophthalmos persisted. By November of
      the same year, his general malaise had increased, and chest X-ray radiography and
      computed tomography were performed on 3rd December. On the basis of the imaging
      results, we suspected active pulmonary tuberculosis of the right upper lobe. The
      smear made by using the sample obtained after bronchial brushing was negative for
      acid-fast bacilli, but a Mycobacterium tuberculosis nucleic acid amplification
      test of the post-bronchoscopic sputum yielded positive results. Therefore, the
      patient was diagnosed with pulmonary tuberculosis. After the 2HREZ/7HR regimen of
      treatment, the extent of the tuberculosis lesions of the lung was reduced and the
      exophthalmos and eye pain were alleviated. Orbital myositis is inflammation of
      the extraocular muscles and can be either idiopathic, without a known etiology,
      or secondary to conditions such as tuberculosis, sarcoidosis, or hyperthyroidism.
      Our patient was not definitively diagnosed with tuberculosis of the eye. A
      definitive diagnosis of tuberculosis of the eye would require detection of
      granulomatous lesions in the eye or isolation of Mycobacterium tuberculosis by
      puncturing the eye muscles; however, our findings suggested the possibility that
      it was secondary to tuberculosis. We think that a careful examination of the
      chest should be performed for patients with ocular abnormalities.

PMID- 22993892
TI  - [Register-based clinical research. Internationally competitive, but the
      difficulties are underestimated].

PMID- 22993893
TI  - [Equality in health care?].

PMID- 22993894
TI  - [New European guidelines on cardiovascular disease prevention].

PMID- 22993895
TI  - [Prolonged bouts of sitting is a metabolic risk factor].

PMID- 22993897
TI  - [X-linked thrombocytopenia with thalassemia in two families in Sweden. Consider
      hereditary causes of thrombocytopenia and bone marrow fibrosis].

PMID- 22993896
TI  - [Anticoagulants in delayed diagnosis of deep venous thrombosis can cause
      compartment syndrome. Cases of misjudged calf pain described].

PMID- 22993898
TI  - [Abdominal compression of the aorta effective in severe postpartum hemorrhage].

PMID- 22993899
TI  - [Medical care for individuals with mental retardation--who takes
      responsibility?].

PMID- 22993900
TI  - [Do not give patients with anorexia nervosa estrogen or birth control pills in
      bone preserving purpose].

PMID- 22993901
TI  - [Remove Tavegyl].

PMID- 22993902
TI  - [Three giants in Bologna].

PMID- 22993903
TI  - [Advances in the diagnosis and treatment of Zollinger-Ellison syndrome].
AB  - Zollinger-Ellison syndrome is a rare disorder caused by tumor secretion of
      gastrin, which results in gastric acid hypersecretion and secondarily in
      complicated peptic ulcer and diarrhea. ZES might be associated with multiple
      endocrine neoplasia type 1. The two main principal therapeutic strategies are to
      control both the gastric acid hypersecretion and the growth of the tumor. Surgery
      often fails to be curative and therefore many patients requires medical therapy,
      mainly treatment with proton pump inhibitors. The aim of this paper was to
      critically discuss contemporary diagnosis and treatment of this neoplasm on the
      basis of progress made in recent years.

PMID- 22993904
TI  - [The influence of swimming activity on lung function parameters among smoking and
      non-smoking youth].
AB  - The aim of the study was to evaluate the influence of regularswimming activity on
      the respiratory system of smokers and non-smokers. MATERIAL AND METHODS: The
      study included 107 students, aged 19 to 24, attending weekly swimming classes.
      The study was composed of the following elements: measurement of selected
      respiratory parameters (FVC, FEV,, MIP, MEP), the percentage concentration of
      blood carboxyhemoglobin (%COHb) and a survey. RESULTS: After 10 months of regular
      swimming activity in the entire study population statistically significant
      increase in maximal expiratory pressure MEP (alpha < 0.02), maximal inspiratory
      pressure MIP (alpha < 0.03) and forced vital capacity FVC (alpha < 0.05) was
      observed. The value of the FEV1 was significantly reduced. CONCLUSIONS: Increased
      respiratory capacity and respiratory muscle strength has been noticed among non
      smokers as well as among smokers. The study confirmed the importance of promoting
      physical activity, especially swimming, among cigarette smokers.

PMID- 22993905
TI  - [Influence of antidepressant therapy on psychic state and functional and
      cognitive abilities elderly patients treated in psychiatric ward].
AB  - Depression and cognitive disfunctions are the most common psychopathological
      disorders of older adults. THE AIM OF THE STUDY: To asses effects of a
      pharmacological and psychological treatment performed in psychiatric ward on
      psychic state and functional and cognitive abilities in elderly patients with
      depression. MATERIAL AND METHODS: The study included group of 35 patients with
      depression (22 women and 13 men) above 65 years old, consecutively admitted to
      the psychiatric ward. Examination of the psychical, mental and functional
      abilities was performed at the beginning and end of 4-6 weeks treatment in
      psychiatric ward, by means of the following scales: Katz activities of daily
      living (ADL), Lawton instrumental activities of daily living scale (IADL),
      Folstein mini mental state examination (MMSE), Yesavage Geriatric Depression
      Scale (GDS). RESULTS: In women, after treatment the average scores in ADL test
      increased 0.3 point (statistically insignificant); in IADL test--increased 2.6
      points (statistically significant); in MMSE test--increased 6 points
      (statistically significant), in GDS scale--reduced 13.45 points (statistically
      significant). In men after therapy the mean value of points in ADL test increased
      0.4 points (statistically insignificant); in the test of IADL increased 3.5
      points (statistically significant); in MMSE test--increased 6.5 points
      (statistically significant); in the scale of the GDS decreased 13.7 points
      (statistically highly significant). CONCLUSIONS: In elderly patients with
      depression mental state improved after pharmacological and psychological
      treatment in psychiatric ward. Improvement of mood in elderly patients treated
      for depression leads to increased functional and cognitive abilities.

PMID- 22993906
TI  - [Severe tricuspid valve injury following blunt chest trauma--case report].
AB  - Tricuspid valve (TV) injury is a rare complication of blunt chest trauma, most
      commonly as a result of a traffic collision. The authors describe a case of
      massive TV regurgitation due to a rupture of the chorde tendinae to the anterior
      and septal leaflets in a 21-year-old man, the victim of a car crash. Concomitant
      organ injuries included, among others, multiple rib fractures, pulmonary
      contusion, open femoral fracture. TV annuloplasty with Medtronic Duran ring
      implantation was performed one year after the accident because of right
      ventricular function worsening and occurrence of right heart failure symptoms.
      Three years after surgery only trivial TV regurgitation is detectable. The
      patient manifest good physical efficiency and continues occupational activity.

PMID- 22993907
TI  - [Portal vein thrombosis as the main symptom of unclassified JAK2-positive
      myeloproliferative neoplasm--case report].
AB  - We report a case of a patient with a diagnosis of myeloproliferative neoplasm,
      unclassifiable, manifested only portal vein thrombosis and followed by cirrhosis
      of the liver. 37-year-old patient, previously healthy, without congenital
      thrombophilia, without prior thrombosis, with normal peripheral blood morphology
      were signs of extensive portal vein system, with massive collateral circulation.
      Patient did not meet the criteria for diagnosis of any of the classic
      myeloproliferative neoplasms. Bone marrow examination revealed hyperplasia and
      presence of single polymorphic megakaryocytes. Positive JAK2V617F mutation status
      was typical for myeloproliferative neoplasm. Therefore, that the portal system
      thrombosis is, sometimes accompanying symptom of other myeloproliferative
      neoplasm, caused by mutations, including polycythemia vera, essential
      thrombocythaemia and primary myelofibrisis, one can assume that between this
      mutation and observed in this patient thrombosis is relationship, despite the
      absence of changes in peripheral blood. This may suggest that we are dealing with
      myeloproliferative neoplasm, in which platelets are indeed produced in normal
      numbers, but they are functionally activated, causing disturbances apparently
      unusual for cancer. This requires confirmation in further studies.

PMID- 22993908
TI  - [The controversies in the diagnosis of polycystic ovary syndrome].
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder in
      women of reproductive age. The main clinical features of PCOS include abnormal
      ovulation, clinical or laboratory indices of elevated androgen levels and
      polycystic morphology of the ovaries. Even though the PCOS was described
      primarily in the 1935 by Stein and Leventhal, to date we are lacking the commonly
      accepted agreement in the issue of diagnosis of this syndrome. Contemporary,
      greater part of clinicians worldwide accept and use the Rotterdam criteria
      published in 2003 for recognizing PCOS, although the National Institute of Health
      criteria (1990) are also popular. Recently, in 2009 Androgen Excess and PCOS
      Society published an upgraded guidelines for recognizing the syndrome. In spite
      the publication of those three statements, interpretation of the three main
      groups of symptoms of the PCOS remain in many aspects controversial. The
      assessment of hyperandrogenisation is highly subjective and can be performed
      using different scoring systems. The matter of measuring androgen levels is
      complicated by the lack of easy accessible and, at the same time, precise
      laboratory method. The ovulation evaluation is also not standardized. The
      evaluation of ovarian morphology, made by ultrasound is problematic, since the
      methods proposed by Rotterdam criteria are very difficult and time-consuming. As
      an result of existing controversies in field of diagnosis of the PCOS, women with
      different phenotypes can be recognized with PCOS by different clinicians. This in
      turn, complicates the treatment and follow-up of those women. In conclusion,
      there is need for a large scientific and clinical research concerning this
      syndrome, to settle improved and more reliable diagnosing criteria.

PMID- 22993909
TI  - [The food cholesterol controversy].
AB  - Arteriosclerosis of blood vessels, the main cause of heart attack and stroke, is
      a disease of multifactor pathogenesis. Multiple experimental, clinical and
      epidemiologic studies indicate that free radicals and lipid oxidation products
      take part in aterogenesis process. Homocysteine possess also cytotoxic activity
      leading to degradation of elastine of internal membrane of blood vessels.
      Deficiency of vitamin folic acid, B12 and B6 cause homocysteine accumulation in
      human organism. Identifying the arteriosclerosis with oxidation of LDL
      cholesterol results with faulty conclusions. Metabolism of cholesterol in human
      organism depends on content of n-6 and n-3 polyunsaturated fatty acids,
      phospholipids, fitosterols, food fiber, Lactobacillus and antioxidants in the
      diet. In aterogenesis antioxidant defficiency, especially long-lasting ones, are
      more important then amount of fat itself. Considering cholesterol intake with
      average food and its absorption amounting 25-30%, one can conclude that amount of
      cholesterol in intestine originates in 90% from liver synthesis, which is
      excreted with bile, and in more than ten percent--from food. This is why
      reduction of cholesterol intake with food only little improves blood lipid
      indexes.

PMID- 22993910
TI  - [Phytic acid--anticancer nutriceutic].
AB  - Phytic acid (IP6) is an inositol-derivative that has undergone phosphorylation
      and belongs to nutraceuticals of the high-fiber diet. This compound has a broad
      spectrum of biological activities, though the in vitro and in vivo anticancer
      activity was described. There has been observed an inhibition of tumor growth and
      induction of cell differentiation in the presence of IP6 in a few cancer cell
      lines including colon, nipple, breast, prostate, cervix, liver, pancreas,
      melanoma and glioblastoma. Molecular mechanisms of the IP6 mediated anticancer
      activity have not been fully specified. According to the current state of
      knowledge there can be only assumed a few ways of action. Antioxidant properties,
      participation in signal transduction, ability to enhance NK-cells, inhibiting
      influence on cell cycle, induction of differentiation in transformed cells and
      activation of programmed death pathways are taken into consideration.

PMID- 22993911
TI  - [Human orgasm from the physiological perspective--part I].
AB  - Physiological phenomenon of sexuality occurring in both sexes that brings
      physical and mental satisfaction, and often affects the quality of life is an
      orgasm. The ability to experience regular orgasms affects relationship with
      partner. The definition of orgasm is not an easy task. The way of experiencing it
      is subjective, and the possibility of observing significantly reduced.
      Contemporary works on the phenomenon of orgasm are concentrated on several
      aspects: biological perspective (neurophysiological and biochemical determinants
      of orgasm), psychological perspective and on the differences in its course in
      both sexes. In sexology are two models of sexual response: a linear model of
      sexual response (by W. Masters and V. Johnson, and H. S. Kaplan) and the circular
      model of sexual response (created by R. Basson). The ability to experiencing an
      orgasm is inherent in men. In women, that phenomenon is acquired, is the
      consequence of further experience.

PMID- 22993912
TI  - [Neuroanatomical structural changes seen in patients with schizophrenia and their
      healthy siblings].
AB  - In studies on the pathogenesis of schizophrenia until last two decades of the
      twentieth century saw advances in knowledge about the neuroanatomical changes. In
      patients suffering from schizophrenia frequently reported enlarged ventricular
      system, the third ventricle enlargement, temporal anomalies of the upper comers
      and irregularities within the frontal lobes. One of the roads leading to the
      understanding of the lesions became also the assessment of changes occurring in
      healthy siblings, used as so-called endophenotype. Almost all the irregularities
      observed in healthy siblings, but to a lesser extent. Typically, their intensity
      was intermediate between siblings suffering and healthy subjects. Further
      research in the future may bring changes identification, typical for the disease,
      which help in the diagnosis of schizophrenia, but also will be helpful in risk
      assessment psychosis clinically healthy individuals.

PMID- 22993913
TI  - [Primary and re-arthroplasty of the hip or knee joints in patients 80 years of
      age and older].
AB  - Due to the ageing of the population, more and more patients older than 80 years
      are in need of the hip and knee joints total endoprosthesis. The aim of this
      retrospective study was to describe perioperative mortality and frequency of
      complications associated with both primary and re-arthroplasty of hip and knee
      joints in this age group. For more information about demography, the
      perioperational period and frequency of complications were investigated 59
      patient's card, who have had a 71 endoprosthesis operations, carried out by one
      surgeon. Information on mortality was obtained by means of telephone
      interviewing. The average level of mortality within 30 days, 1 year and 5 years
      amounted to 2.0, 6.1 and 10.2% respectively. Compared with other studies
      conducted over the past 20 years, these results reflect a significant reduction
      in the mortality, rate. Average frequency of complications in our study was to
      52.2%. which corresponds to the previously published data. All the complications
      were eliminated and did not cause permanent disability. Thanks to the development
      of anaesthesia, surgical techniques and technologies, joint endoprosthetics can
      be considered safe in patients older than 80 years.

PMID- 22993914
TI  - [The difficulties of using intubating laryngeal mask in a patient with
      concomitant morbid obesity].
AB  - This is a case report of tracheal intubation with Intuhating Laryngeal Mask
      (ILMA) in a patient with morbid obesity.

PMID- 22993915
TI  - [Spinal neurosurgical intervention in a patient with end-stage renal disease
      (ESRD)].
AB  - The article presents the description of clinical observation, in which spinal
      neurosurgical intervention was successfully made in a patient with ESRD,
      receiving chronic hemodialysis for 20 years. In this context, we discuss the
      various clinical and tactical aspects of the management of patients with this
      severe co-pathology: infusion-transfussion therapy, peculiarities of anesthetic
      management and intra-operation monitoring, diagnostics and correction of
      hemostasis disorders, hemodialysis organization.

PMID- 22993916
TI  - [Ketamine versus propofol during one-lung ventilation in thoracic surgery].
AB  - A comparative analysis of gas, the metabolic rate, pressor, resistive and
      volumetric characteristics of pulmonary blood flow, central and intracardiac
      hemodynamics in patients undergoing thoracic surgery was conducted. 2 methods of
      anesthesia maintenance: on the basis of ketamine - fentanyl - pipecuronium and
      propofol - fentanyl - pipecuronim were compared. Invasive monitoring system
      PiCCOplus for the behaviour of the transpulmonary thermodilution (TT) in
      combination with VoLEF for the pulmonary thermodilution (PT) the change of
      ventilation mode ALV - OLV - ALV was used. OLV lasted for more than 1.5 hours.

PMID- 22993917
TI  - [Iliofascial versus epidural block during hip endoprosthesis].
AB  - The study was carried out to compare analgesia, the side-effects incidence and
      the need for analgetics when you use the continuous iliofascial block (CIFB)
      versus epidural analgesia (EA) after the total hip joint endoprosthesis (THJEP).
      60 patients undergoing planned THJEP under spinal anaesthesia were included in a
      randomized controlled study. The day before the surgery all patients were divided
      into 2 groups (30 people each). In the 1st group postoperative analgesia carried
      out on the basis of the EA, and in the 2nd group - CIFB. All patients received
      balanced analgesia with nonopioid analgesics, and in case of pain syndrome -
      tramadol injections. In the 1-st group the value of the visual-analogue scale -
      VAS (0-100mm) 6 h after the operation was significantly lower at rest and in
      motion. The maximum average value of VAS in motion was 2.3 +/- 2, 1 mm in EA
      group and 3.2 +/- 2.6 mm in CIFB group. Frequency of tramadol use in 1-st and 2
      nd groups was 6.9% and 41.4%, and of nausea - 34,5% and 6.9%, respectively.
      Patient analgesia satisfaction was higher in the 2nd group. CONCLUSION: Extended
      IFB provides a good level of analgesia in patients after THJEP. Prolonged EA
      exceeds CIFB in analgesia, but is accompanied by a greater frequency of
      postoperative nausea occurrence.

PMID- 22993918
TI  - [The effect of the cervical plexus block on anti-nociceptive protection during
      surgeries on the interior carotid arteries].
AB  - MATERIALS AND METHODS: 77 anaesthesia protocols during a. carotis interna (ACI)
      operations were analyzed. All the patients were divided into 3 groups. In the 1
      st group a total intravenous anaesthesia - TIV4 (propofol and fentanyl) was used.
      In the 2nd and 3rd groups was used combined anaesthesia: in the 2nd - TIVA +
      superficial CPB, in the 3rd - combined anesthesia (sevortane+fentanyl+CPB). When
      analyzing the results, BP, BIS data, anaesthetic doses and the need for opioid
      analgesics were evaluated. Assessment of the postoperative pain quality was
      conducted within 48 hours of the postoperative period on a verbal assessment
      scale (VAS). RESULTS: The need for fentanyl was considerably higher in the 1st
      group. The analysis of the BP data dynamics showed better stability in the 2nd
      and 3rd groups. CONCLUSIONS: TIVA + CPB provides better analgesia and reduces the
      need for opioid analgesics; greater stability of hemodynamic parameters during
      operation stages, as well as the best brain perfusion during a. carotis interna
      occlusion; postoperative analgesia and allows to avoid the early appointment of
      systemic analgesics.

PMID- 22993919
TI  - [Correction of early cognitive disorders in school-age children operated under
      total intravenous anaesthesia].
AB  - The aim of the study was to assess the possibility and effectiveness of hopaten
      acid use for early postoperative cognitive dysfunction correction in children of
      school age. MATERIALS AND METHODS: In compliance with inclusion and exclusion
      criteria, totally 40 children of school age (7-16 years old, ASA status I-II)
      with surgical pathology: (varicocele, cryptorchidism, inguinal hernia) were
      included A comperative assessment of neuropsychic status during pre - and
      postoperative are period in children, operated under propofol-fentanyl total
      intravenous anesthesia (TIVA) was conducted All patients were randomized to the
      control (without cepebroprotection 1st group, 20 children) and experimental
      (using cepebroprotection with hopaten acid within 1 month after the operation,
      2nd group, 20 children) groups. Dimension of the study: Harvard standard
      monitoring, respiratory gas composition, neuropsychic tests (Bourdon test, "10
      words test", etc.). RESULTS: For full compatibility groups (age, ASA status and
      anthropometric data, equal operation duration and the equipotential drug dosage
      adjustment is revealed, that in group of propofol-fentanyl TIVA in the early
      postoperative period in school age children postoperative cognitive dysfunction
      (POCD) is developing, which in case of absence of the corresponding correction is
      maintained after 1 month after operation (at least) in 80% of cases. In the
      application of hopaten acid cerebroprotection (40 mg/kg per day) severity of POCD
      reliably is reduced or compensated by the time of discharge from the hospital (3
      7-th day when non-traumatic interventions), and 1 month after the operation in
      30% of patients experienced improvement of cognitive functions, which proves the
      effectiveness of hopaten acid for POCD treatment. CONCLUSION: In case of propofol
      fentanyl TIVA anesthesia in children of school age is indicated preventive
      prescription of multimodal cerebroprotectors without age limitations (for example
      hopaten acid (40 mg/kg per day) for POCD treatment.

PMID- 22993920
TI  - [Options for remodeling of the right ventricular function during pneumonectomy].
AB  - The aim of the study---a comprehensive assessment of haemodynamic alterations
      during pneumonectomy using pulmonary arterial volumeter (PAV) opportunities.
      MATERIALS AND METHODS: 72 patients were included in the study, (the average age -
      51 +/- 3,8 years, body weight - 68 +/- 7 kg), who underwent pneumonectomy about
      lung tumors under general anesthesia with separate ventilation (on indications -
      jet high-frequency ventilaton).

PMID- 22993921
TI  - [Pathophysiology of recruit ventilation and its effect on the respiration
      biomechanics (review of the literature)].
AB  - In patients with acute respiratory distress syndrome (ARDS) lungs consist of
      aeration zones and zones of alveolar collapse, which lead to intrapulmonary
      shunting and hypoxemia. ALV may increase alveolar collaps and potentially lead to
      lung damage arising out of displacing surfaces tension between aerated and
      collapsed lung parts and re-closing and opening of the alveoli. Based on the
      strategy of the "open lung" the recruitment maneuver can be used to achieve the
      alveolar recruitment, while PEEP prevents alveolar collapse. There are many
      recrutment types, including a long inflated to a higher pressure, reccuring
      breath, gradual increase of PEEP, and PIP etc. Data on the use of recruitment in
      ARDS patients, show varied results with increased efficiency in patients with
      early ARDS, good complaisance of the chest and extrapulmonary Genesis of lung
      damage. In this review, we discuss the pathophysiological basis of recruitment
      use, recent evidence and contradictions of the application of this method.

PMID- 22993922
TI  - [The autonomous nervous system and blood circulation system--homeostasis and
      homeokinesis during spine surgery].
AB  - In 30-surgical patients, operated for degenerative-dystrophic changes of the
      spine (microdiscectomy), with due regard for initial condition of the ANS
      (differentiated by Kerdo index), homeokinesis state has been studied. The
      circulatory system function was controlled with the use of a standard monitoring
      and central hemodynamics indices, that has allowed to mark out Hyper-and Hypo -
      eukinetic circulation types. Microdiscectomy performed under combined anesthesia
      (N2O/ O2 - 0.5) with fentanyl and sevorane. It was found that 68% of the surveyed
      patients directly before the surgery had a lack of homeokinesis (vagotonia).
      Comparison of the reaction of the autonomous nervous system and the circulatory
      system to premedication revealed that the change in the number of vagotonic
      patients and patients with hypokinetic type of hemodynamics had a direct linear
      dependence, and the number of sympathotonic patients and patients with
      hypokinetic type of hemodynamics -- the reverse one. Surgery, intraoperative
      pharmacological load, change of the body in sympathotonic patients accompanied
      with changes in Central hemodynamics (low afterload, eukinetic HI values),
      characteristic for physiological homeokinesis, which was not observed in
      vagotonic patients, which have remained unsuccessful (dysadaptative) hypokinetic
      type of blood circulation.

PMID- 22993923
TI  - [Haemostasis disturbances as the component of the surgical stress-response and
      possibilities of their correction].
AB  - OBJECTIVE: An estimation of haemostasis parameters in the major abdominal surgery
      in comparision with surgical stress-response markers depending on anaesthesia and
      analgesia technique. METHODS: 120 patients scheduled to undergo elective low
      abdominal surgery were allocated to receive either general anaesthesia (n=40) or
      combined (general + epidural (n=40) or general + spinal (n=40)) anaesthesia.
      Postoperative analgesia, glucose, cortisol and cytokine levels, as well as
      coagulation, fibrinolysis, thrombocyte aggregation parameters were estimated.
      RESULTS: The epidural anaesthesia provided better postoperative analgesia.
      However both spinal and epidural anaesthesia show comparable correction of
      surgical stress-response markers. Also both types of regional anaesthesia reduced
      hypercoagulation expression and prevented fibrinolysis activation. This resulted
      in a reduction in the hemotransfusion frequency CONCLUSION: Hemostasis changes
      can be considered as a component of the surgical stress-response. The role of
      intraoperative regional anaesthesia is much more significant, than postoperative
      analgesia.

PMID- 22993924
TI  - [Acid-base disturbances during liver transplantation].
AB  - Objective of the study is to assess the contribution of different factors in the
      development of acid-base disturbances at the stages of liver transplantation.
      MATHERIALS AND METHODS: The analysis of right lobe relative liver transplantation
      was held in 86 recipients. 22 patients corresponded to ASA III (group 1), ASA IV 
      50 patients (group 2), and ASA V - 14 patients (group 3). Blood samples were
      studied by pH, SB, lactate, pCO2 at the stages: up to the beginning, before v.
      cava inferior cross-clamping, before blood flow launch, on the 1st minute after
      blood flow launch, 5 min after blood flow launch. 1 hour after the blood flow
      launch, 2 hours after blood flow launch, at the end of operations. Cardiac index
      and oxygen delivery were also estimated RESULTS: The preliverless stage was
      characterized by a decrease in pH, SB. BE and increased lactate, oxygen delivery
      slightly reduced due to the reduction of oxygen blood capacity, cardiac index
      remained within the normal range. During liverless period, the growth rate of
      lactate was different in all three groups, DO2 was below the norm, CI - on the
      lower bound of the norm. Blood flow launch was accompanied by a peak values of
      pH, SBC, BE, lactate and increased pCO2. CONCLUSIONS: The main factor in the
      development of metabolic acidosis during preliverless stage is lactate growth as
      a consequence of decreased hepatic lactate clearance and blood loss. During
      liverless period the most significant impact contributes to reduced cardiac
      output, which, together with reduced oxygen blood capacity leads to a decrease in
      tissue DO2. Increased production of lactate, together with a decrease in its
      clearance due to liver shutdown from the bloodstream leads to higher rates of
      lactate growth in this period. When starting the blood flow in addition to the
      release of acidic substances, growth of endogenous CO2 leads to the peak pH
      values.

PMID- 22993925
TI  - [Endogenous heparin-like syndrome: analysis of clinical observations].
AB  - One of the reasons for non-surgical bleeding is heparin-like syndrome (HLS),
      under which is understanded presence of heparin effect in the absence of it's
      exogenous application. The role of endogenous heparins perform glycosaminoglycans
      -- biologically active substances. HLS is accompanied by endothelium damage and
      discussed in the network of the systemic inflammatory response syndrome (SIRS).
      HLS is described in liver future, sepsis, pregnancy and a number of
      hemoblastosis. Hypocoagulation effect of endogenous heparin localizates in X
      coagulation factor. The main method of diagnosis - thromboelastography. The use
      of a specific heparin antidote - Protamine sulfate has not confirmed clinical
      efficacy. Priority direction in the therapy of - methods of "shunt hemostasis".
      In this paper, we present the analysis of observations of 4 patients with
      developed endogenous HLS. In 2 cases (combination of sepsis with hepatic failure
      in one patient and initial thrombophilia in other) HLS has been accompanied by
      massive bleeding (massive hemothoraxc with haemorrhagic shock, a massive
      intraoperative blood loss). For HLS relief in these cases was used prothrombine
      complex concentrate (PCC) (in the 1st case), recombinant VIIa factor (in the 2nd
      case). In other cases, HLS (in a patient with multiple myeloma and childbirth in
      the postpartum period), haemorrhagic syndrome was not so expressed, the treatment
      was carried out with FFP transfusion.

PMID- 22993926
TI  - [Prognostic criteria for tracheostomy in the neuroresuscitation unit].
AB  - The aim is to specify prognostic criteria for tracheostomy on the basis of long
      term (more than 14 days) ALV and prolonged (more than 14 days) trachea
      canmulation. MATERIALS AND METHODS: Retrospectively were analyzed the medical
      history of 120 difficult patients with tracheostomy, who spent in ICU more than
      72 hours. Was executed multiple logistic regression analysis. RESULTS: In
      patients with consciousness level of 8 or less points on the Glasgow coma scale
      and subarachnoid hemorrhage, detected on CT scan of the brain, increases the
      chances for prolonged ALV versus patients without these signs in 3.93 times. In
      patients with constrained basal cisterns, detected on CT scan of the brain and to
      the consciousness level of 8 or less points on the Glasgow coma scale versus
      patients without these signs increases the chances of the prolonged trachea
      cannulation in 5 times. CONCLUSION: Prognostic criteria for tracheostomy in
      patients in neuroresuscitation unit are: criteria for prolonged ALV: level of 8
      or less points on the Glasgow coma scale and subarachnoid hemorrhage and criteria
      for prolonged trachea cannulation: constrained basal cisterns, detected on CT
      scan of the brain and to the consciousness level of 8 or less points on the
      Glasgow coma scale.

PMID- 22993927
TI  - [Some of criteria in the evaluation of severity and prognosis with different
      forms of acute pancreatitis].
AB  - The aim of the research is to improve diagnosis and assessment of severity and
      prognosis with different forms of acute pancreatitis. In 79 patients were studied
      levels of leukocytes, lymphocytes, leucocyte intoxication index (LII), the
      content of lactate dehydrogenase (LDG), creatinephosphokinase (CPK), amylase,
      aspartate aminotransferase (AST, alanine aminotransferase (ALT). RESULTS: The
      level of leukocytes reflects the severity of the disease, but had no prognostic
      value. The level of lymphocytes, LII. LDG and lipase reflect the severity, of the
      disease and have prognostic value. The level of amylase, AST, ALT, CPK not always
      reflect the severity of the disease, but had prognostic value. CONCLUSION: The
      most readily available to assess the severity and prognosis in acute pancreatitis
      are the level of blood lymphocytes and LII. Indicators LDG. CPK, amylase, lipase,
      AST and ALT also reflect the course and prognosis of the disease.

PMID- 22993928
TI  - [Use of integral two-frequency impedanciometry in clinical monitoring in patients
      with acute destructive pancreatitis].
AB  - The paper gives the results of studying the body water compartments and impedance
      parameters in 69 patients with acute destructive pancreatitis during
      postoperative period, by means of non-invasive integral two-frequency
      impedancometry. Progressing extracellular hyperhydratation and decreased total
      electrical impedance of body tissue accompanied by increased number of general
      and intraabdominal complications, mortality, that determine the prognostic
      significance of these criteria.

PMID- 22993929
TI  - [Modern aspects of diabetic ketoacidosis treatment in children].
AB  - The aim of the research - the analysis of the regularities of diabetic
      ketoacidosis treatment in children and adolescents with type 1 diabetes mellitus,
      the explanation of the results obtained with the use of biological systems
      stability theory elements. MATHERIALS AND METHODS: The study included 90 children
      with type I diabetes mellitus in a state of diabetic ketoacidosis of different
      severity degree. With newly diagnosed type 1 diabetes mellitus - 56 children,
      with the "courced" diabetes - 34 children. In the evaluation of patients status
      was defined glucose, pH, and other indicators of acid-base status, using gas
      analyzer GEM Premier 3000 ("Instrumental laboratory", USA). RESULTS: All children
      received treatment under the Protocol, approved by the Moscow Health Department,
      withdrawn from the state of diabetic ketoacidosis without any complications. In
      the basis of this methodology is application of glucose solutions and "small"
      doses of insulin from the start of infusion therapy in spite of hyperglycemia.
      This therapy helps to prevent cerebral edema against the background of gradually
      reduce the blood glucose. pH recovery was explained by the existence of a common
      pathophysiology process. Given the qualitative description of this process on the
      basis of biological systems stability theory. Were determined 3 stationary state:
      pH = 7.4 and pH < 6,9; and one is unstable, called "the point of no return" - pH
      = 6.9. The conclusions of this theory substantiate the effectiveness of
      ketoacidosis treatment with offered method CONCLUSION: The offered technique for
      diabetic ketoacidosis treatment on the basis of the glucose solutions infusion
      throughout the treatment and "small" doses of insulin values pH and glucose in a
      safe range, even in patients with high risk of brain edema, which is confirmed by
      biological systems stability theory.

PMID- 22993930
TI  - [Effect of clarithromycin on the systemic inflammatory response syndrome severity
      in patients after myocardial revascularization surgery].
AB  - The aim is to investigate the effectiveness of SIRS pharmacological correction in
      patients after CABG when adding clarithromycin to the standard antibacterial
      therapy. Patients of the 1st group (n=25) received Klacid- CP ("Abbott") in
      perioperative period plus to standard antibacterial therapy (3rd generation
      cephalosporins), patients of 2nd group received standard therapy. At 1st
      screening stage, as well as on the 2-nd and 4-th day after operation were
      recorded data of an anamnesis, concomitant pathology, examination, were measured
      the level of white blood cells, LII, biochemical blood analysis (CRP), defined
      the concentration of interleukins (IL-1, 6, 8,10,12) and TNF - a. In all studied
      patients, laboratory' and physical data did not go beyond the reference values,
      intraoperation data, blood loss and ALV duration did not statistically differ.
      According to the results of research in patients of both groups there were
      manifestations of SIRS in the form of reliable significant increase in body
      temperature, as well as the level of Il-6, IL-8, CRP, LII, TNF - a, leukocytosis.
      While in the clarithromycin group body temperature was significantly lower in all
      time points. The level of CRP for the 4th day in 1.5 times, and TNF in 4 times
      less than in the control group, and the values of anti-inflammatory IL-10 to the
      2nd day, on the contrary almost in 2 times higher than those in the control
      group. Thus, the obtained data confirmed that the CABG is accompanied by non
      inflammatory SIRS development. At the same time clarithromycin gives an
      independent proven anti-inflammatory effect and can be recommended for
      application in the schemes of prophylactic antimicrobial therapy during
      perioperative period in this category of patients.

PMID- 22993931
TI  - [Hemostasis during MARS therapy and hemodiafitration in patiens with acute renal
      hepatic failure].
AB  - OBJECTIVE: to study the dynamics of the haemostatic system, depending on
      coagulopathy type and efferent therapy method (HDF, MARS) in patiens with acute
      renal-hepatic failure. As a complex of intensive therapy, all the patients were
      trated extracorporeal techniques: HDF therapy in group I (n = 121) and MARS in
      group 1 (n = 62). Patients were aged from 18 to 67 years. RESULTS AND DISCUSSION:
      MARS - is an effective therapy and has effects on haemostasis system: observed
      recovery of platelet-vascular disorders of coagulation and haemostasis. HDF is
      effective in patients with coagulation type of laboratory disseminated
      intravascular coagulation (DIC), and was dangerous in fibrinolytic DIC type
      because of haemostasis status decompensation risk.

PMID- 22993932
TI  - [Malignant hyperthermia in a child (case report)].
AB  - This case report describes the malignant hyperthermia (MH) accident in 12-year
      old boy undergoing maxillary-facial surgery: Crisis began 30 min after normal
      sevoflurane induction. Patient was successfully treated hence the MH exhibited
      abortive course. One should considerthis case as urgent reason for dantrolen
      registration in Russia, because it is not officially available yet. And it also
      demonstrates the necessity for more vigilant relation to the MH especially in
      pediatric anaesthesiology.

PMID- 22993933
TI  - [Investigation of structural characteristics of initial substances of ibuprofen
      and micronization impact].
AB  - Structural characteristics of ibuprofen substances manufactured by different
      firms and the impact of micronization on them were compared. The study showed
      that the use of X-ray diffraction methods was necessary for certification of
      medicinals (crystalline) since only such methods provided information on the
      substance crystal structure, the molecular state and polymorphous forms.

PMID- 22993934
TI  - [Cycloferon use in complex therapy of children with salmonellosis and yersiniosis
      infection].
AB  - The efficacy of cycloferon in complex therapy of salmonellosis and yersiniosis in
      children (n=220) was investigated under clinical and laboratory conditious. It
      was shown, that cycloferon had direct and indirect immunotropic action in
      salmonellosis and yersiniosis in children. In contrast to the conventional
      antibiotic therapy, the use of cycloferon provided a more rapid relief of the
      local and systemic symptoms, reduction of superinfection or exacerbation. It had
      a positive effect on the antiinfective resistance of the colon mucosa resulting
      in normalization of the colon lumen microecology. The use of cycloferon provided
      eradication of the pathogen and opportunistic organisms. In the treatment of
      salmonellosis it enhanced formation of rare bacterial reconvalescent Shigella.

PMID- 22993936
TI  - [Immunotropic agents in therapy of chronic degenerative diseases of the vulva].
AB  - The prospective randomized study involved 60 patients with chronic dystrophic
      diseases of the vulva. The clinical efficacy of cycloferon in the complex
      treatment of the patients and its influence on the psychological and functional
      state and the dynamics of the life quality were investigation.

PMID- 22993935
TI  - [Microbiological monitoring in therapy of patients with iatrogenic
      esophageotracheal fistula].
AB  - The results of the microbiological diagnosis of infective inflammatory
      complications in patients with iatrogenic esophageotracheal fistula and the
      tactics of their antibacterial prophylaxis and therapy within a 9-year
      observation period (2003-2011) were analysed. The main organisms colonizing the
      tracheobronchial tree in the patients were S. epidermidis, S. aureus, enteric
      bacteria, P. aeruginosa and Candida. An increase of the S. epidermidis resistance
      to rifampicin, moxifloxacin and especially ciprofloxacin was observed. The
      resistance of S. aureus did not significantly change. Within the observation
      period, high susceptibility of all the Staphylococcus isolates to vancomycin and
      linezolid remained stable. Among the nonfermenting gramnegative bacteria, the P.
      aeruginosa isolates were the most frequent and characterized by a lower portion
      of the isolates with preserved susceptibility to the agents (except polymyxin B)
      known earlier as antipyocyanic antibiotics, i.e. to imipenem and cefepim. Since
      the proportion of P. aeruginosa in the etiology of pyoinflammatory processes in
      the region of esophageotracheal fistula ranged within 9.3 to 17.5%, the fact
      should be considered in the antibiotic therapy. There was observed an increase in
      the frequency of infectious complications due to other nonfermenting gramnegative
      bacteria (acinetobacters) and first of all A.baumannii. Various Candida isolates
      were characterized by dependence of the susceptibility on the selective pressure
      of irrational therapy, as well as their species (the presence of such species as
      C. Krusei and C. glabrata with natural resistance), that required not only the
      species identification but also determination of the Candida isolates resistance
      in every particular case.

PMID- 22993937
TI  - [Efficacy of azithromycin and its impact on cytokine system in urogenital
      infections].
AB  - Seventy five patients with urogenital chlamydial and mycoplasmic infections were
      enrolled in the trial. In the etiotropic therapy azithromycin was used in the
      standard dosage (1.0-1.5 g) depending on the infection. The treatment with
      azithromycin, in addition to the high eradication rates, was also evident of its
      effect on the cytokine levels in the patients, that was characteristic of a
      significant increase of the IFN-gamma level and a decrease of the IL-1beta and IL
      6 levels in the blood.

PMID- 22993938
TI  - [Perspectives of tigecycline treatment of surgical site infections in oncologic
      patients].
AB  - Criteria of tigecycline (Tygacil) use for the treatment of surgical site
      infections in oncologic inpatients were developed. High efficacy of tigecycline
      in vitro and in vivo against multiresistant hospital strains persistent in the
      surgical department of the gastrointestinal oncologic division was shown.

PMID- 22993939
TI  - [Adequate empiric therapy of nosocomial fungal infections in oncologic patients
      of intensive care units].
AB  - The results of a 3-year experience with voriconasole in oncologic practice are
      presented. Rational schemes for the use of caspofungin and mycofungin in the
      treatment of oncologic inpatients and the criteria of their use in the therapy of
      fungal nosocomial infections were developmed. Good clinical and microbiological
      efficacy of caspofungin and mycofungin against Candida non-albicans was shown.

PMID- 22993940
TI  - [Criteria of antibacterials choice for prophylaxis and therapy of implant
      associated infections in prosthetic joints].
AB  - Prosthetic joints infection is a serious medical, social and financial problem.
      Significant achievements in prophylaxis of such infections are well known. In
      cases of primary endoprosthetics of large joints, the frequency of infection in
      the leading world clinics is 0.5-2%. However, the approaches to the treatment of
      such infections are different especially with respect to the antibacterial
      therapy: choice of drugs, administration routes, treatment course and
      discontinuation. Under conditions of global growth of resistance in nosocomial
      pathogens, the choice of antimicrobials requires consideration not only of the
      formal susceptibility criteria, but also of the pharmacokinetic and
      pharmacodynamic indices.

PMID- 22993941
TI  - [Acquired androgen deficiency in men with chronic cardiac failure].
AB  - This review concerns the role of acquired androgen deficiency in pathogenesis of
      chronic cardiac failure (CCF) in men. It shows that patients with CCF and CHD
      suffer reduced testosterone production that correlates with impaired contractile
      activity of myocardium. It means that androgen deficiency due to combined
      bronchopulmonary and cardiovascular pathology promotes the early development of
      CCF.

PMID- 22993942
TI  - [Acute pleural empyema: modern methods of treatment].
AB  - The prinicipal methods (conservative, surgical, parasurgical) for the treatment
      of acute pleural empyema are discussed with special reference to antibacterial
      and immunotherapy and surgical operations.

PMID- 22993943
TI  - [Mechanical jaundice of calculous etiology].
AB  - The current rise in the incidence of cholelithiasis is accompanied by an
      increased frequency of its complicated forms. Mechanical jaundice is a common
      unfavourable complication of cholelithiasis and choledocholithiasis, its
      consequence. Epidemiology, etiology, and clinical features of this disease are
      discussed Classification of mechanical jaundice is proposed Much attention is
      given to its pathogenetic mechanisms. Methods of laboratory and instrumental
      diagnostics as well as approaches to the surgical treatment of mechanical
      jaundice are described

PMID- 22993944
TI  - [Clinical and morphological parallels in lung lesions associated with hemorrhagic
      fever with renal syndrome].
AB  - The authors report the results of clinical examination of the respiratory, organs
      of 97 patients with hemorrhagic fever and renal syndrome (HFRS) with confirmed
      Puumala serotype. Retrospective analysis of 16 fatal cases is presented. It is
      shown that patients with moderately severe and severe forms of the disease
      exhibit early clinical and X-ray signs of pulmonary lesions and respiratory
      insufficiency Some of them suffer acute respiratory distress syndrome confirmed
      by morphological findings at autopsy.

PMID- 22993945
TI  - [Prognostic significance of cardiac rhythm variability in patients with chronic
      heart failure].
AB  - Prognosis of chronic heart failure (CCF) is a challenging clinical problem. The
      role of heart rhythm variability (HRV) in CCF pathogensis is poorly known. This
      study was aimed at estimating the possibility of using HRV for prognosis of CCF.
      It included 110 patients (mean age 55.1 +/- 6.4 yr) with CCF symptoms after
      myocardial infarction. HRV analysis was based on 5 minute records. During the
      first year; 44 patients developed cardiovascular complications, 20 aggravation of
      CCF 5 unstable angina, 7 repeated infarction, 9 died. The low-frequency component
      (LF) of the spectrum was inversely related to age, HR, NT-proBNP, CRP and left
      ventricular election fraction. Based on the low-frequency component median, the
      patients were allocated to 2 groups (less than 5.2 ln ms2 and 5.2 ln ms2 or
      more). Comparison of survival curves by the Kaplan-Meier method showed that at LF
      < 5.2 ln ms2 the probability of CCF decompensation (p = 0.03), secondary
      infarction (p = 0.007), lethal outcome (p = 0.03) is significantly higher than at
      LF of 5.2 ln ms2 or more. It means that LF < 5.2 ln ms is an independent risk
      factor of CCF decompensation, repeated myocardial infarction, amd lethal outcome.

PMID- 22993946
TI  - [Structural and functional changes in myocardium of patients with chronic heart
      failure treated with spironolactone].
AB  - The aim of the work was to study structural and functional characteristics of the
      left ventricle (LV) and diastolic function in patients with systolic chronic
      heart failure (CCF). Group 1 included 34 patients with LV systolic dysfunction
      (ejection fraction > 45%) treated with spironolactone (verospiron) at 25-50
      mg/day. Group 2 of 30 untreated patients served as control. Echo CG was performed
      by routine method in the M-modal regime. Combination of diastolic (DD) and
      systolic (SD) dysfunction was documented in 20 (31.2%) patients, restrictive type
      in 27 (42.2%). Spironolactone had beneficial effect on structural and functional
      characteristics of myocardium. It significantly increased LV ejection fraction
      from 23.8 +/- 7.4% in the beginning of the study to 43.3 +/- 8.6% 12 months later
      (p < 0.05). During 12 month, patients with systolic CCF showed positive dynamics
      of LV diastolic dysfunction. The number of patients with normal LV configuration
      increased within 6 months after the onset of therapy from 11.7 to 26.6% (p <
      0.05). However, the difference was insignificant by the end of the study. The
      number of patients in group 1 with eccentric hypertrophy increased from 64.7 to
      75.0% after 12 months (p < 0.05) but that with concentric hypertrophy decreased
      The data obtained suggest the necessity of early beginning of spironolactone
      therapy of CCF hearing in mind its positive effect on diastolic dysfunction.

PMID- 22993947
TI  - [Specific features of left ventricular remodeling in patients with diabetes
      mellitus and coronary heart disease residing in the Far North].
AB  - This study enrolled 202 patients with diabetes mellitus and coronary heart
      disease residing in the Far North. They were selected from 8753 subjects included
      in the Registry of performed coronary angiographies. The control group contained
      196 patients with CHD and DM2 residing in the south of Tyumen region. 76 (19%)
      patients had normal structural and functional characteristics of LV (LVMM = < N
      and LVRWT < 0.45), in 322 (81%) these characteristics were pathologically changed
      (eccentric and concentric LV hypertrophy, concentric LV remodeling). Groups 1 and
      2 included 79.2 and 68.4% men respectively p = 0.014) of mean age 53.9 +/- 0.45
      and 58.1 +/- 0.51 p < 0.001) having LV diameter 26.2 +/- 0.2 mm and 25.5 +/- 0.2
      mm (p = 0.012). Other echocardiographic parameters, occurrence of asymmetric
      myocardial hypertrophy, and distribution of the patients by the types of LV
      geometric models were not significantly different. Odd ratios for the patients
      with pathological LV morphology revealed no dependence of LV remodeling on the
      site of residence. The structural and functional changes in myocardium of the
      patients residing in the North and South of Tyumen region were comparable in
      terms of severity. It is concluded that DM is a powerful factor influencing
      myocardial remodeling to the extent that masks even the effects of extreme
      ("northern") environmental conditions.

PMID- 22993948
TI  - [Relationship between endothelial and erectile functions in patients with
      coronary heart disease].
AB  - The study included 92 men with stable coronary heart disease (CHD) aged 39-61
      (mean 55 +/- 5.3) years. Groups 1 and 2 were comprised of 63 patients with
      erectile dysfunction (ED) and 29 ones without it respectively. It was shown that
      most patients with CHD suffer ED (68.5%). The probability of ED increases in the
      presence of such risk factors as diabetes mellitus, multifocal atherosclerosis,
      disturbances of lipid metabolism. Severity of ED grows with CHD duration and body
      mass. Parameters of endothelium-dependent dilation of brachial and cavernous
      arteries were impaired in ED patients which suggests the compromised ability of
      these vessels to respond to mechanical deformation. ED is a marker not only of
      functional disturbances of the vascular tone but also of severity of
      atherosclerotic lesions. Correlation analysis revealed the relationship between
      mean endothelium-dependent dilation of brachial artery and severity of ED; the
      latter also correlated with such markers of cardiovascular risk as multifactor
      atherosclerosis, obesity, and disturbances of lipid metabolism.

PMID- 22993949
TI  - [The recovery of cognitive functions in the patients with organic brain disorders
      as a component of combined rehabilitation with the use of the method of
      bioacoustic correction].
AB  - This study was designed to follow up dynamics of the recovery of cognitive
      functions after comprehensive medical rehabilitation of the patients with organic
      brain disorders using a bioacoutsic correction technique. A peculiar feature of
      this method is it allows for involuntary self-regulation of the functional state
      of the central nervous system and therefore can be used to treat patients
      experiencing cognitive problems. It was shown that the application of the method
      of bioacoustic correction promotes restoration of cognitive functions, reduces
      anxiety, and normalizes parameters of electroencephalograms.

PMID- 22993950
TI  - [Relationship between changes in brachiocephalic arteries and osteoporosis in
      women with rheumatoid arthritis].
AB  - This study included 50 women with rheumatoid arthritis (mean age of 50.6 +/- 6.4
      years) examined by duplex scanning of brachiocephalic arteries and double-energy
      X-ray absorptiometry. 56% of patients had changes in brachiocephalic arteries, 62
      % suffered osteoporosis and osteopenia. The inverse relationship between the
      thickness of the intima-media complex of brachiocephalic arteries and bone
      mineral density in the proximal part of the femur and lumbar spine was
      documented.

PMID- 22993951
TI  - [Signs of hypercoagulation and activation of fibrinolysis in patients with
      Wegeners's granulomatosis and Schoenlein-Genoch's purpura].
AB  - The patients with Wegener's granulomatosis and Schoenlein-Genoch's purpura
      included in this study were examined in the E.A.M. Tareev Clinic during 2006
      2008. They showed signs of hypercoagulation and activation of fibrinolysis, viz.
      enhanced SFMC, D-dimer and antiphospholipid antibody levels, platelet
      aggregation. Hypercoagulation correlated with the activity of both Wegeners's
      granulematosis and Schoenlein-Genoch's purpura.

PMID- 22993952
TI  - [Application of magnetic resonance tomography of the body and multispiral
      computed tomography to the estimation of the extent of the osteodestructive
      process in patients with multiple myeloma].
AB  - We compared the efficacy of detection of osteodestruction sites by X-ray magnetic
      resonance tomography (MRT) and multispiral computed tomography (MSCT) in 11
      patients with multiple myeloma. X-ray study revealed sites of destruction from 7
      to 40 mm in size in all the 11 patients. MSCT using a 64-slice tomograph showed
      skeletal bone destruction (5-53 mm) and revealed soft-tissue component of the
      tumour in 2 patients. MRT revealed destruction sites 4-50 mm in size and soft
      tissue tumour component in all the patients. The use of MSCT allowed detecting
      affected sites in cortical and trabecular layers of the bone. MRT revealed the
      largest number of affected size and their visualization was more efficacious than
      by two other methods.

PMID- 22993953
TI  - [Changes in the immune status of patients operated for splenic lesions in the
      late postoperative period and their relation to the development of
      complications].
AB  - This analysis of changes in the immune status of patients operated for splenic
      lesions is based on the observations of 126 subjects. Fifty of them underwent
      autolientransplantation and 26 conservative surgery. The main parameters of
      humoral and cellular immunity were measured along with changes in the microflora.
      Splenectomy was shown to cause changes in the characteristics of both cellular
      and humoral immunity. Autolientransplantation caused a significant decrease in
      the serum level of total complement and its C3- and C-4 fractions while the
      amount of circulating immune complexes increased All other parameters of the
      immune status remained unaltered The best outcome of the treatment was documented
      after conservative surgery.

PMID- 22993955
TI  - [Peculiarities of stable angina of effort in aged and elderly patients].
AB  - A total of 4141 patients complaining of chest pain were divided into 7 groups.
      They were examined for the analysis of heart pain, cardiac rhythm disturbances,
      and chronic heart failure. Peculiarities of stable angina of effort in aged and
      elderly patients are described

PMID- 22993954
TI  - [Personalized reamberin therapy in patients with decompensated LADA 1.5 diabetes
      mellitus].
AB  - The aim of the study was to develop a new strategy of dosing a Reamberine 1,5%
      infusion solution on an individual basis for patients with LADA 1.5 diabetes
      mellitus (DM) and new methods for estimating the regulation and functioning of
      metabolic pathways associated with the production and transformation of succinic
      acid. The use of Reamberin led to the reduction of average, maximum and minimum
      blood glucose and HBA1c levels. The study revealed a decrease of proteinuria,
      serum creatinine level, and albumin/creatinine ratio in urine Patients given
      intensive therapy with insulin and Reamberin underwent significant reduction of
      blood Na', K+ and chlorine levels and increased Na+/K+, Mg++ and Ca++ ratios.
      Morning and evening concentrations of ACTH decreased while cortisol levels
      increased at 8.00 and 18.00. IRI level decreased, T3 and T4 levels increased both
      at 8.00 and 18.00 when TSH concentration was reduced The percentage of patients
      unsatisfied with QL (based on the Diabetes QL scale) among those taking
      Reamberine diminished while that of the patients satisfied with QL increased. The
      first data on dynamics of plasma protein expression during Reamberin therapy are
      presented

PMID- 22993956
TI  - [Successful rituximab therapy of HCV-cryoglobulinemic vasculitis with severe
      ulcerative and necrotic lesions of the skin].
AB  - This clinical observation demonstrates successful rituximab therapy of HCV
      cryoglobulinemic vasculitis with severe ulcerative and necrotic lesions of the
      skin on the lower extremities. Vasculitis recurred 3 years after the persistent
      virological response had been achieved and complete clinical remission resulted
      from antiviral therapy. Possible causes of vasculitis relapses in the absence of
      HCV viremia are discussed with reference to the difficulties encountered in
      managing this condition.

PMID- 22993957
TI  - [Atypical clinical course of Cushing's disease].
AB  - Endogenous hypercorticism is a severe endocrine disease with clinical symptoms
      resulting from long-term action of corticosteroids. In this country, conditions
      caused by the excess pituitary ACTH production are called Itsenko-Cushing
      disease. In the absence of adequate treatment, half of the patients die within 5
      years after the onset of the disease. Correct diagnosis prior to the development
      of severe complications significantly improves its prognosis and patients'
      quality of life. It is generally believed that endogenous hypercorticosm must be
      accompanied by pathognomonic symptoms that may be helpful in establishing the
      diagnosis. However, certain patients present with non-specific symptoms of little
      diagnostic value. We report a case of Itsenko-Cushing disease lacking in specific
      symptoms of hypercorticism.

PMID- 22993958
TI  - [The beginning of Emperor Nikolai Saratov University (1909-1917)].

PMID- 22993959
TI  - Social class, politics, and the spirit level: why income inequality remains
      unexplained and unsolved.
AB  - Richard Wilkinson and Kate Pickett's latest book, The Spirit Level: Why Equality
      is Best for Everyone, has caught the attention of academics and policymakers and
      stimulated debate across the left-right political spectrum. Interest in income
      inequality has remained unabated since the publication of Wilkinson's previous
      volume, Unhealthy Societies: The Afflictions of Inequality. While both books
      detail the negative health effects of income inequality, The Spirit Level expands
      the scope of its argument to also include social issues. The book, however, deals
      extensively with the explanation of how income inequality affects individual
      health. Little attention is given to political and economic explanations on how
      income inequality is generated in the first place. The volume ends with political
      solutions that carefully avoid state interventions such as limiting the private
      sector's role in the production of goods and services (e.g., non-profit sector,
      employee-ownership schemes). Although well-intentioned, these alternatives are
      insufficient to significantly reduce the health inequalities generated by
      contemporary capitalism in wealthy countries, let alone around the world.

PMID- 22993960
TI  - Neoliberalism is bad for our health.
AB  - This paper examines some of the concerns that arise from the impact of
      neoliberalism on health and health care. It also examines the way that global
      institutions such as the World Health Organization and the World Trade
      Organization, having been captured by neoliberalism, fail to act decisively to
      reduce poverty and inequality and thereby do all too little to promote population
      health at a global level. The paper argues for a greater community focus, with
      health care systems being seen more as social institutions and placing more power
      over decision making in the hands of a critically-informed citizenry.

PMID- 22993961
TI  - Wealth inequality and health: a political economy perspective.
AB  - Despite a plethora of studies on income inequality and health, researchers have
      been unable to make any firm conclusions as a result of methodological and
      theoretical limitations. Within this body of research, there has been a call for
      studies of wealth inequality and health. Wealth is far more unequally distributed
      than income and is conceptually unique from income. This paper discusses the
      results of bivariate cross-sectional analyses of the relationship between wealth
      inequality (Gini coefficient) and population health (life expectancy and infant
      mortality) in 14 wealthy countries. The results confirm that wealth inequality is
      associated with poor population health. Both unweighted and weighted correlations
      between wealth inequality and health are strong and significant, even after
      controlling for a variety of potential aggregate-level confounders, including
      gross domestic product per capita, and after excluding the United States, the
      most unequal country. The results are strongest for female life expectancy and
      infant mortality. The author outlines potential pathways through which wealth
      inequality might affect health, using specific countries to illustrate. The
      article concludes with policy recommendations that could contribute to a more
      equitable distribution of wealth and, ultimately, decreased health disparities.

PMID- 22993962
TI  - The politics of avoidable blindness in Latin America--surgery, solidarity, and
      solutions: the case of Mision Milagro.
AB  - Avoidable blindness, especially when caused by cataracts, is a disease primarily
      of the economically disadvantaged sectors of the population. With a focus on
      Latin America and the Caribbean, this paper focuses on the program Mision Milagro
      within its historical, political, and economic contexts. This initiative, led by
      the governments of Cuba and Venezuela, covers close to 35 countries across Latin
      America, the Caribbean, Asia, and Africa. It is well-known throughout Latin
      America as close to 2 million patients have undergone free screening, corrective
      surgery, and rehabilitation since its inception in 2004. Mision Milagro shows
      that implementation of a massive initiative to curb avoidable blindness caused by
      cataracts in a relatively short time is feasible. The program is also built upon
      a unique model of international cooperation, which stresses social objectives and
      solidarity rather than hegemonic international initiatives built on commercial
      relationships. It also provides elements that could be applied to other public
      health issues of global or national relevance, not only to other low-middle
      income countries, but also to high-income countries such as Canada.

PMID- 22993963
TI  - Reconstructing the critically damaged health service system of the country.
AB  - India's ruling class, in association with international agencies, bureaucrats,
      and business interests, has formed a powerful syndicate that has been imposing
      its will on the country to the detriment of public health. After gaining
      independence, India developed a body of knowledge suited to its social, cultural,
      economic, and epidemiological conditions. This led to an alternative approach to
      public health education, practice, and research that foreshadowed the Alma Ata
      Declaration on Primary Health Care of 1978. In the early 1980s, global power
      shifts undermined national and international commitment to the Declaration.
      Wealthy countries' response to the declaration of self-reliance by economically
      disadvantaged countries was swift: an effort to suppress the Declaration's ideals
      in favor of an unscientific, market-driven agenda. As a result, public health
      practice in India virtually disappeared. Responding to growing restiveness among
      a population in need, political leaders have launched the foredoomed National
      Rural Health Mission and pursued an American brand of public health through the
      Public Health Foundation of India. Reconstructing the damaged public health
      system will require pressure on the syndicate to ensure India's public health
      heritage will be used to effectively transfer "People's health in people's hands"
      according to the guidelines set down at Alma Ata.

PMID- 22993964
TI  - Speculation on commodities futures markets and destabilization of global food
      prices: exploring the connections.
AB  - In December 2010, the United Nations Food and Agriculture Organization's Food
      Price Index surpassed its previous peak of June 2008, and prices remained at this
      level through September 2011. This pattern is creating justified fears of a
      renewal or intensification of the global food crisis. This paper reviews
      arguments and evidence to inform debates on how to regulate commodity futures
      markets in the face of such price volatility and sustained high prices. We focus
      on the relationship between market liquidity and price patterns in asset markets
      in general and in commodities futures markets in particular, as well as the
      relationship between spot and futures market prices for food. We find strong
      evidence supporting the need to limit huge increases in trading volume on futures
      markets through regulations. We find that arguments opposing regulation are not
      supported. We find no support for the claim that liquidity in futures markets
      stabilizes prices at "fundamental" values or that spot market prices are free of
      any significant influence from futures markets. Given these results, the most
      appropriate position for regulators is precautionary: they should enact and
      enforce policies capable of effectively dampening excessive speculative trading
      on the commodities markets for food.

PMID- 22993965
TI  - Poverty and the violation of human rights: a proposed conceptual framework.
AB  - The paper proposes a conceptual framework linking the causes of poverty with the
      causes of human rights violations. Both are presented as outcomes of a cascading
      chain of determinants grouped as immediate, underlying, and basic causes. The
      framework will make situation analyses focused on poverty and human rights better
      adjusted to the reality on the ground. It is also the first step in using the
      human rights-based approach, now an established methodology being used by a
      growing number of health and development practitioners and seen by the United
      Nations system as the way forward. The framework also provides guidance to
      communities in identifying, in a participatory way, causes of the problems that
      affect them. The framework is presented in a diagram format followed by a list of
      the major determinants in each causal level.

PMID- 22993966
TI  - Employer-sponsored health insurance erosion accelerates in the recession.
AB  - From 2000 to 2009, the share of non-elderly Americans covered by employer
      sponsored health insurance (ESI) fell 9.4 percentage points. Although the economy
      was already in a recession in 2008, it continued to dramatically deteriorate in
      2009. From 2008 to 2009, the unemployment rate rose 3.5 percentage points, the
      largest one-year increase on record. As most Americans under age 65 rely on
      health insurance obtained through the workplace, it is no surprise that ESI fell
      sharply from 2008 to 2009 at a rate three times as high as in the first year of
      the recession. Over the 2000s, no demographic or socioeconomic group has been
      spared from the erosion of job-based insurance. Both genders and people of all
      ages, races, education, and income levels have suffered declines in coverage.
      Workers across the wage distribution, in small and large firms alike, and even
      those working full-time and in white-collar jobs have experienced losses. Along
      with sharp declines in ESI, the share of those under age 65 without any insurance
      increased 3.3 percentage points from 2000 to 2009. Increasing public insurance
      coverage, particularly among children, is the only reason the uninsured rate did
      not rise one-for-one with losses in ESI.

PMID- 22993967
TI  - Ditching the single-payer system in the national health service: how the English
      Department of Health is learning the wrong lessons from the United States.
AB  - Reforms to the British National Health Service introduce major changes to how
      health care will be delivered. The core elements include the creation of new
      purchaser organizations, Clinical Commissioning Groups, which unlike their
      predecessors will be able to recruit and reject general practices and their
      patients without geographical restriction. The Clinical Commissioning Groups are
      to transition from statutory bodies to freestanding organizations, with most of
      their functions privatized and an increasingly privatized system of provision, In
      this paper, we explore the likely consequences of these proposals, drawing in
      particular on the experience of managed care organizations in the United States,
      whose approach has influenced the English proposals extensively. We argue that
      the wrong lessons are being learned and the English reforms are likely to
      fundamentally undermine the principles on which the British National Health
      Service was founded.

PMID- 22993968
TI  - Response to "An unexpected mortality increase in the United States follows
      arrival of the radioactive plume from Fukushima: is there a correlation"?
AB  - The author responds to an article published in the Journal by Joseph J. Mangano
      and Janette D. Sherman suggesting that an increase in U.S. deaths shortly after
      Japan's Fukushima nuclear plant accident could be attributed to radiation from
      this accident arriving in the United States. The author writes that the cause of
      these deaths has not been analyzed and that there is no known mechanism for low
      dose radiation to cause acute death in infants or adults. The author also notes
      that the cities under study with the lowest radiation fallout have the highest
      increases of death rates in the 14 weeks following Fukushima, while the
      Californian cities that would have received larger doses saw a decrease in death
      rate growth. He concludes that innumerable factors other than radiation likely
      are responsible for the bulk of the measured effect.

PMID- 22993969
TI  - Response to "An unexpected mortality increase in the United States follows
      arrival of the radioactive plume from Fukushima: is there a correlation"?
AB  - The author responds to an article published in the Journal by Joseph J. Mangano
      and Janette D. Sherman suggesting that a large increase in U.S. deaths soon after
      Japan's Fukushima nuclear plant accident could be caused by radiation released
      from this accident and arriving in the United States. This author attributes the
      increase to the authors' inclusion of a higher number of cities in their study
      before and after Fukushima (119 and 104 cities, respectively).

PMID- 22993970
TI  - Response to "An unexpected mortality increase in the United States follows
      arrival of the radioactive plume from Fukushima: is there a correlation"?
AB  - The author responds to an article published in the Journal by Joseph J. Mangano
      and Janette D. Sherman suggesting that a large increase in U.S. deaths within
      days after Japan's Fukushima nuclear plant accident could be attributed to
      radiation released from this accident and arriving in the United States. This
      response posits that exposure to such extremely low doses of ionizing radiations
      cannot cause immediate deaths. The author argues that it is extremely unlikely an
      increase in U.S. deaths immediately after the Fukushima and Chernobyl nuclear
      plant accidents is caused by radiation released from these sites.

PMID- 22993971
TI  - Response to the Institute of Medicine's recommendation that cost determine
      insurance policies' "essential benefits".
AB  - An open letter to U.S. Secretary of Health and Human Services Kathleen Sebelius,
      signed by 2,425 individuals, including 1,280 U.S. physicians, protests the
      recommendations of an Institute of Medicine committee on the "essential benefits
      package" to be offered by health plans under the 2010 federal health reform act.
      The letter also criticizes conflicts of interest in the Institute of Medicine
      committee, which includes executives from two of the nation's largest health
      insurance firms and a major donor to the Institute.

PMID- 22993972
TI  - [Establishment of Dao-Di index and its significance in quality control and
      rational usage of Chinese medicine].
AB  - There exists numerous indices for quality evaluation and control in Chinese
      medicinal materials. However, most of these indices are qualitative and non
      interrelated each other, as well as having little relationship with safety and
      efficiency. In this article, we first establish a comprehensive evaluating index-
      Dao-Di index (DDI) based on five factors: relative history of producing areas,
      ecological suitability of producing areas, commercial specification and grade,
      golden rate of main components, and biopotency/ toxic potency. This DDI can be
      used to guarantee the quality of Chinese medicinal materials more
      comprehensively, objectively and effectively, promoting the integration of
      'species-quality-property-effect-usage', and it will provide significant
      references and revelation for taking a world leading role of quality control
      standard for tranditional medicines.

PMID- 22993973
TI  - [Advances in studies on classification of Bupleurum].
AB  - This article introduced the herbal medicine studies on Bupleurum in recent years,
      focused on the classification just like morphological and chemical
      classification, microscopic characteristics and molecular biology classification
      for Bupleurum. Identification combined with a variety of classification is the
      most effective method for Bupleurum. Due to the short supply of Bupleurum in the
      current market the current Bupleurum classification studies should focuses on
      combining pharmacological research to expand the Bupleurum's herbal sources.

PMID- 22993974
TI  - [Karyotype analysis and its systematic implications of Pterocypsela formosana and
      P. elata].
AB  - Pterocypsela is a very important traditional Chinese medicine from the tribe
      Cichorieae of Asteraceae. Mitotic chromosome numbers and karyotypes are reported
      for P. formosana and P. elata from Hunan and Hubei province, China. The former is
      new and the latter provide confirmation of previous reference. All P. taxa are
      diploidy with 2n = 18 and their basic number is tentatively suggested as x = 9.
      Karyotype of Pterocypsela is 2A and P. formosana with a karyotype formula of 2n =
      2x = 18 = 4m + 14sm, and 2n = 2x = 18 = 2m + 8sm +8st for P. elata. It is the
      first time to report the AI value for Pterocypsela in this paper. Cytological
      data of chromosomal numbers and karyotypes were used to discuss the close
      relationships of the Pterocypsela genus and the taxonomy of the medicinal plants.

PMID- 22993975
TI  - [Isolation of endophytic bacteria in roots of Panax ginseng and screening of
      antagonistic strains against phytopathogens prevalent in P. ginseng].
AB  - In this study, endophytic bacteria were isolated from roots of P. ginseng by
      plate culture method, and as a result, 40 endophytic bacterial strains were
      isolated, Bacillus spp. and Pseudomonas spp. were predominant. By confront
      culture method, two antagonistic endophytic bacterial strain, ge15
      (Stenotrophomonas maltophilia) and ge25 (Bacillus sp. ) against Cylindrocarpon
      destructans, Sclerotinia schinseng and Alternaria pana were identified. The
      inhibition zone of ge15 to them were 5.5, 22.0, 14.8 mm, respectively; and which
      were 12.7,16.5,9.0 mm for ge25. The Results indicate that endophytic bacteria
      have biocontrol potential on ginseng pathogens, and which can be used as a bio
      control factor on ginseng soilborne diseases control.

PMID- 22993976
TI  - [Comparative studies on scavenging DPPH free radicals activity of flavone C
      glycosides from different parts of Dendrobium officinale].
AB  - OBJECTIVE: To study the scavenging DPPH free radicals activity of flavone C
      glycosides from different parts of Dendrobium officinale. METHOD: The types and
      contents of flavonoids from different parts of D. officinale were analyzed by TLC
      and HPLC. The antioxidant effect was tested by scavenging DPPH free radicals
      activity. RESULT: The stems, leaves and flowers contained the same type of
      flavone C-A glycosides and 8 common peaks were identified. The content of flavone
      C-A glycosides was significantly different. The content of flavone C-glycosides
      in leaves and flowers was higher than that in stems. The flavonoid in roots was
      less. Stems contained naringenin, which was not identified in root, leave and
      flower. Both stems and leaves had antioxidant capacity of eliminating DPPH free
      radicals, of which scavenging DPPH free radicals activity of leaves was better
      than stems. CONCLUSION: Considering the content of flavonoid and antioxidant
      activity leave and flower of D. officinale may substitute stems. The study
      provides a preliminary basis for the development and utilization of leave and
      flower of D. officinale.

PMID- 22993977
TI  - [Dynamic accumulations of bioactive components in different germplasm Isatis
      indigotica and comparative of its quality of medical material].
AB  - OBJECTIVE: To study the dynamic accumulations of bioactive components in
      different germplasm Isatis indigotica and compare its quality of medical
      material, in order to provide a basis for breeding and high yield cultivation of
      I. indigotica. METHOD: The planting samples were collected during growth period,
      bioactive components in different germplasm Isatis indigotica were measured.
      RESULT: The dynamic accumulations of bioactive components in different germplasm
      I. indigotica were consistently changed in a field experiment. The differences of
      bioactive components contents in medical material of I. indigotica were
      significant. CONCLUSION: The germplasm from Gansu Longxi showed a high yield and
      good quality characters in Fuyang area, and may be applied to production.

PMID- 22993978
TI  - [Pollen morphological characteristics, viability test and storage of endangered
      medicinal plant Atractylodes lancea].
AB  - OBJECTIVE: To study the pollen morphological characteristics, viability test and
      storage character of the endangered plant Atractylodes lancea. METHOD: Pollen
      grains morphologies of A. lancea were observed by scanning electron microscope.
      The optimum culture medium and viability determination methods were screened out
      by liquid culture and dyeing methods, and then the pollen germination capacities
      in different storage conditions were detected. RESULT: The pollen grains are
      quasi-spherical, with tricolpate and spinous sculpture. The optimal culture
      medium was ME3 + 16% PEG4000 + 10% sucrose, in which the pollen germination
      capacity reached to 62.1%, while the other three dyeing methods were not able to
      be applied to detecting the pollen viability of A. lancea. The low storage
      temperature could significantly prolong the storage time of pollen of A. lancea.
      At -80 degrees C, pollen viability could be maintained for 60 days. CONCLUSION:
      Liquid culture method is suitable for the determination of pollen germination of
      A. lancea, and the rate of pollen germination is closely related to the storage
      time and temperature. At last, this study provides a foundation for the
      artificial pollination and cultivating in wildness of A. lancea.

PMID- 22993979
TI  - [Genetic relationship on several medicinal plants in Marsdenia from Yunnan in
      ISSR marker].
AB  - OBJECTIVE: To analyze the genetic relationship of 9 Marsdenia species from
      Yunnan, especially the traditional Dai medicine "Dai Bai Jie" (M. auricularis).
      METHOD: Applying the inter-simple sequence repeats (ISSR) markers technology.
      RESULT: Twenty-five primers were screened out of 60 ISSR random primers and
      produced 391 bands totally, every primer produce 8-21 bands and the mean number
      was 15.6. The range of the GS (genetic similarity) value was 0.6675-0.8210. In 9
      Marsdenia species, M. auricularis is a relative of M. tenacissima. M. balansae
      and M. officinalis have the closest genetic relationship. CONCLUSION: It is
      supported by ISSR that the M. auricularis which is sib species of M. tenacissima,
      and the folk medicine of Marsdenia are worthy deep investigation and study.

PMID- 22993980
TI  - [Method for discriminating key quality control indicators of concentrated
      solution before traditional Chinese medicine ethanol precipitation].
AB  - OBJECTIVE: To suggest a method for discriminating quality control indicators of
      concentrated solution before traditional Chinese medicine ethanol precipitation.
      METHOD: The second ethanol precipitation (SEP) of Guanxinning was taken as an
      example, with the concentrated supernatant of first ethanol precipitation (CSFEP)
      prepared with same dry matter content and the same amount of ethanol as raw
      materials, to conduct the ethanol precipitation test under the same conditions.
      The experimental data was analyzed by stepwise regression and partial least
      squares regression. Both of them selected the parameters which affect phenolic
      compounds retention ratios in SEP supernatant as the key indicators. RESULT:
      Phenolic compounds contents in SEP supernatant were mainly affected by the
      contents of danshensu, caffeic acid and salvianolic acid B in CSFEP. CONCLUSION:
      The discrimination method can be used to discover key quality control indicators
      of concentrated solution before ethanol precipitation.

PMID- 22993981
TI  - [Identification of hydrolysates and alcoholysates of aconitum alkaloids].
AB  - OBJECTIVE: To identify products decomposed in high temperature water and alcohol
      from diester alkaloids such as aconitum alkaloid, in order to study their
      transformation regularity. METHOD: Structures of multiple converted products were
      determined by analyzing on multistage mass spectrometry of known compounds and
      literature searching. RESULT: Benzaconine and pyraconitine were the major
      hydrolysates, while pyraconitine and ethoxy-aconitine were the major
      alcoholysates from diester alkaloids. CONCLUSION: Pyraconitine alkaloids, as
      pyrolytic products, are not related to the type of solvent. 8-ethoxy-aconitine
      alkaloids, as alcoholysates, are related to the type of solvent. This study
      identifies multiple converted products from alkaloids and summarizes mass
      spectrometry fragmentation regularity by LC-MS, laying a firm foundation for
      studies on the transformation of toxic diester alkaloids contained in aconitum
      and providing a basis for studies on the transformation of alkaloids contained in
      aconitum during boiling.

PMID- 22993982
TI  - [Difference of volatile constituents contained in female and male flowers of
      Trichosanthes kirilowii by HS-SPME-GC-MS].
AB  - OBJECTIVE: To compare and analyze volatile constituents from flowers of
      Trichosanthes kirilowii, in order to point out characteristic differences between
      female and male flowers. METHOD: Blooming female and male flowers were collected
      in the same place. Volatile constituents were extracted from the flower by solid
      phase micro-extraction (SPME), then separated and analyzed by gas chromatography
      mass-spectrometry (GC-MS). RESULT: Fifty-two and forty-five chromatographic peaks
      were separated from the female and male flowers, respectively. Forty seven
      constituents were identified and their relative percentage compositions were
      determined with the peak area normalization method. Linalool, alpha-farnesene,
      benzene methanol, and (Z)-2-methylbutanal oxime were the main volatile
      constituents. The contents of linalool and alpha-farnesene in female flower were
      remarkably higher than those in male. In contrast, the content of benzene
      methanol in male flower was remarkably higher than that in female. CONCLUSION: In
      the first study on chemical constituents from flowers in genus Trichosanthes, 37
      compounds are separated from T. kirilowii. Contents of linalool, alpha-farnesene
      and benzene methanol show the characteristic differences of volatile constituents
      contained in male and female flowers of T. kirilowii, which enriches the basic
      studies on dioecious plant.

PMID- 22993983
TI  - [Optimization of vinegar processing technique of Euphorbia pekinensis by multi
      index orthogonal test].
AB  - OBJECTIVE: To optimize the vinegar processing technique of Euphorbia pekinensis.
      METHOD: The test was designed by using orthogonal table L9 (3(4)). The factors
      were vinegar amount, proportion of vinegar and water and duration and degree of
      heating. An aggregative weighted method was used to optimize processing
      technology of E. pekinensis with content of euphol, extract of ethanol, extract
      of water and appearance and section were used as evaluative indicators. RESULT:
      The optimal processing of E. pekinensis was identified as adding the mixture of
      30 g vinegar and 270 g water to 100 g herbs, mixing evenly and softening, cooking
      until exhaustion under slow fire, taking out and drying to degree 6-7, and then
      cutting into thick slices. CONCLUSION: The study defines parameters of the
      processing technique of E. pekinensis. The quality of E. pekinensis is stable and
      controllable under the technical conditions.

PMID- 22993984
TI  - [Chemical constituents contained in Tetraena mongolica].
AB  - To study chemical constituents contained in Tetraena mongolica. Chemical
      constituents were separated and purified by using such methods as silica gel,
      Toyopearl HW-40C and HPLC preparative chromatography. Their structures were
      identified by organic spectral method. One new compound was separated from T.
      mongolica and identified olean-11-oxo-12-en-28-ol-3beta-yl-caffeate.

PMID- 22993985
TI  - [Trace chemical constituents contained in Trachelospermum jasminoides and
      structure identification].
AB  - OBJECTIVE: To study trace chemical constituents contained in traditional Chinese
      medicine Trachelospermum jasminoides. METHOD: The chemical constituents were
      separated and purified by using such column chromatographic methods as ployamide,
      silica gel, Sephadex LH-20 and ODS, and their structures were identified on the
      basis of spectral data analysis. RESULT: Eleven compounds were separated from T.
      jasminoides and identified as bergenin (1), chrysoeriol-7-O-beta-D-glucoside (2),
      arctigenin-4'-O-beta-gentiobioside (3), matairesinol 4'-O-beta-gentiobioside (4),
      traxillagenin (5), traxillaside (6), 4-demethyltraxillagenin (7), luteolin-7-O
      beta-gentiobioside (8), arctiin (9), trachelogenin-4'-O-beta-gentiobioside (10)
      and luteolin-7-O-beta-D-glucoside (11). CONCLUSION: Compounds 1 and 2 were
      separated from Trachelospermum genus for the first time, while compounds 3-7 were
      separated from this plant for the first time.

PMID- 22993986
TI  - Sesquiterpene lactones from Inula helianthus-aquatica.
AB  - OBJECTIVE: To investigate the sesquiterpene lactones of the aerial parts of Inula
      helianthus-aquatica. METHOD: Compounds were isolated and purified by silica gel,
      Sephadex LH-20 and preparative HPLC. On the basis of physicochemical properties
      and spectroscopic data, their structures were identified. RESULT: Seven
      sesquiterpene lactones and four other compounds were obtained and identified as 2
      desoxy-4-epi-pulchellin (1), 6-acetoxy-4-hydroxy-1, 10H-pseudoguaia-11 (13)-en
      12,8-olide (2), 4-acetoxy-6-hydroxy-1, 10H-pseudoguaia-11(13)-en-12,8-olide (3),
      8-epi-inuviscolide (4), 2,3,11,13-tetrahydroaromaticin (5), 11,13-dihydro
      ergolide (6), 4-epipulchellin-2-O-acetate (7), 7-epiloliolide (8), loliolide (9),
      beta-sitosterol (10) and daucosterol (11). CONCLUSION: All the compounds were
      isolated from this plant for the first time.

PMID- 22993987
TI  - [Caffeoylquinic acid derivatives from the seeds of Vernonia anthelmintica].
AB  - Mature seeds of Vernonia anthelmintica were separated and purified by using such
      methods as macroporous absorption resin, Sephadex LH-20 and HPLC preparative
      chromatography. Six compounds were obtained and their structures were identified
      by such spectrum techniques as 1H, 13C-NMR and MS. Compound 1-6 were identified
      as caffeic acid (1), 3-O-caffeoylquinic acid (2), 4-O-caffeoylquinic acid (3), 5
      O-caffeoylquinic acid (4), 3, 4-di-O-caffeoylisoquinic acid (5), 3, 4-di-O
      caffeoylquinic acid (6). Among them, compounds 1-6 were separated from this plant
      for the first time, while compounds 3-5 were separated from this genus firstly.

PMID- 22993988
TI  - [Chemical constituents of Neoalsomitra integrifoliola].
AB  - OBJECTIVE: To study the chemical constituents of the n-BuOH fraction of 95%
      ethanolic extract of leaves of Neoalsomitra integrifoliola. METHOD: The compounds
      were isolated with kinds of column chromatography. The structures were determined
      by MS and NMR spectroscopic techniques. RESULT: Eight compounds were isolated
      from the n-BuOH fraction of 95% ethanolic extract and their structures were
      identified as 2-phenylethyl rutinoside (1), rutin (2), kaempferol-3-O-alpha-L
      rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3), isorhamnetin-3-O-alpha-L
      rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (4), methyl chlorogenate (5),
      guanosine (6), adenosine (7), myo-inositol (8), respectively. CONCLUSION: All
      compounds were isolated from this genus for the first time.

PMID- 22993989
TI  - [Chemical constituents of petroleum ether extract of fruits of Schisandra
      sphenanthera].
AB  - OBJECTIVE: To study the chemical constituents in the fruits of Schisandra
      sphenanthera. METHOD: The constituents were isolated by their silica gel column,
      Sephadex LH-20 gel column, and their structures were elucidated by their chemical
      properties and spectroscopic analyses. RESULT: Twelve compounds were isolated and
      identified as (+)-anwulignan (1), deoxyschizandrin (2), interiotherin A (3),
      schisantherin A (4), beta-sitosterol (5), schisantherin D (6), 4
      hydroxybenzaldehyde (7), 6-O-benzoylgomisin O (8), schizandronic acid (9),
      schisanlactone D (10), schisanlactone B (11), kadsulactone A (12). CONCLUSION:
      Compounds 3, 7, 10-12 were obtained from this plant for the first time.

PMID- 22993990
TI  - [Identification and secondary metabolites of endophytic fungal strain PR35 from
      Paeonia delavayi].
AB  - OBJECTIVE: To identify the endophytic fungal strain PR35 separated from Paeonia
      delavayi and study chemical constituents of its secondary metabolites. METHOD:
      The fungal strain PR35 was identified by morphological observation and ITS rDNA
      sequence analysis. Various chromatographic methods were adopted to separate and
      purify its secondary metabolites, and their structures were identified by
      physiochemical properties and spectral data RESULT: The fungal strain PR35 was
      identified as Trichoderma longibrachiatum. Five compounds were separated from
      fermentation products of fungal strain PR35 and identified as 1-(2,6
      dihydroxyphenyl)-3-hydroxybutan-1-one (1), 1-(2,6-dihydroxypheny) propan-1-one
      (2), 1-(2,4,6-trihydroxyphenyl) butan-1-one (3), 4-methoxy-1-naphthol (4), and
      cerevisterol (5). Among them, compounds 1-3 showed notable antifungal activities
      against Botrytis cinerea, Fusarium avenaceum and Hormodendrum compactum.
      CONCLUSION: The endophytic fungus T. longibrachiatum was separated from the plant
      P. delavayi for the first time. Five compounds were first separated from
      endophytic fungus of P. delavayi. Among them, compound 4 was separated from
      microbial fermentation products for the first time.

PMID- 22993991
TI  - [Quantitative determination of sibricose A5 and sibricose A6 in Polygalae radix].
AB  - OBJECTIVE: To establish the method for quantitative determination of sibricose A5
      and sibricose A6 in Polygalae Radix by HPLC. METHOD: The ultrasonic extracting
      method was applied in sample pre-treatment. The HPLC procedure was performed on
      the chromatographic column of Agela Promosil C18 (4.6 mm x 250 mm, 5 microm), the
      mobile phase was acetonitrile-0.1% phosphoric acid water solution (10:90). The
      detection wavelength was 330 nm and flow velocity was 1 mL x min(-1). The column
      temperature was 30 degrees C. RESULT: The method has good linearity in the ranges
      of 0.0087-0.0694 g x L(-1) (r = 0.9993) for sibricose A5, 0.0090-0.0723 g x L(-1)
      (r=0.9991) for sibricose A6. The average recoveries of sibricose A5 and sibricose
      A6 were 101.7%, 97.87%, with the RSD of 1.7%, 1.6%, respectively. CONCLUSION: The
      method was simple, quick accurate and reliable. It is appropriate for the
      quantitative determination of sibricose A5 and sibricose A6 in Polygalae Radix.

PMID- 22993992
TI  - [HPLC-ELSD fingerprint of Marsdenia tenacissima from different habitats].
AB  - OBJECTIVE: To establish a HPLC-ELSD fingerprint of Marsdenia tenacissima from
      different habitats, in order to provide a reliable method for scientific
      assessment and effective quality control. METHOD: HPLC-ELSD was adopted to
      determine 25 baches of M. tenacissima herbs from different habitats. Traditional
      Chinese medicine chromatographic fingerprint similarity software assessment
      system 2004 developed by China Pharmacopoeia Committee was adopted to establish a
      common mode chart and assess chromatographic similarity based on the degree of
      correlation. RESULT: The common mode for M. tenacissima herb C21 steroidal
      fingerprint was established, including 11 common characteristic peaks. Among
      them, 10 were identified. According to the assessment on the similarity of 25
      batches of samples, 80% of them showed a similarity of over 0.80 in steroidal
      HPLC-ELSD fingerprint. CONCLUSION: The method can be used to assess the quality
      of M. tenacissima.

PMID- 22993993
TI  - [Investigation of a compound, compatibility of Rhodiola crenulata, Cordyceps
      militaris, and Rheum palmatum, on metabolic syndrome treatment I--improving
      insulin resistance].
AB  - To investigate the effects of a compound (FF16), compatibility of Rhodiola
      crenulata, Cordyceps militaris, and Rheum palmatum, on insulin resistance. The
      results showed that FF16 significantly improved the insulin sensitivity through
      decreasing AUC values in insulin tolerance tests by 24.1%, 38.5%; reducing the
      levels of serum insulin by 46.0%, 30.4%, of HOMA-IR by 52.4%, 81.2%; and
      reversing the lower GIR values by 119.3%, 202.4% in IRF mice and KKAy mice,
      respectively. In addition, in KKAy mice, the value of whole body insulin
      sensitivity index (ISWBI) was enhanced by 1.0 times, the abilities of the insulin
      induced glucose uptake in liver, adipose and skeletal muscle were enhanced by
      1.5, 2.8 and 2.2 times, respectively, in FF16-treated mice comparing with those
      in model mice. The recombinant human protein tyrosine phosphatase 1B (PTP1B)
      activity was inhibited by FF16 in vitro with the IC50 value of 0.225 mg x L(-1).
      The increased PTP1B expression in the liver was also reversed by 45.8% with the
      administration of FF16 in IRF mice. In conclusion, FF16 could improve insulin
      resistance by inhibiting the activity of PTP1B.

PMID- 22993994
TI  - [Mechanisms for inhibition effects of polypeptide extract from scorpion venom
      (PESV) on proliferation of A549 cell lines in vitro].
AB  - OBJECTIVE: To investigate the mechanisms for inhibition effects of PESV on
      proliferation of non-small cell lung cancer cell line A549. METHOD: MTT was used
      to observe cell growth and proliferation of A549 at different concentrations of
      PESV. Flow cytometry (FCM) was applied to analyze cell cycle distribution.
      Immunocytochemistry and western blot assay was recruited to detect the expression
      of VEGF, HIF-1alpha, PTEN after the intervention of PESV. RESULT: A549 cells may
      be arrested mainly in G0/G1 phase and cell proliferation was significantly
      inhibited (P < 0.01) after PESV intervention in a certain range of concentration.
      PESV can significantly reduce the expression of HIF-1alpha,VEGF and increase the
      expression of PTEN. CONCLUSION: PESV can block cell cycle and inhibit
      angiogenesis directly to inhibit cell proliferation of non-small cell lung cancer
      cell line A549 mainly through reducing the expression of HIF-1alpha, VEGF and
      increasing the expression of PTEN.

PMID- 22993995
TI  - [Effect of different channel ushering drugs on homing of bone marrow stem cells
      of femoral head necrosis model rabbits].
AB  - OBJECTIVE: To observe the effect of Huogu II formula compatible with different
      channel ushering drugs on the homing of bone marrow stem cells of osteonecrosis
      of the femoral head (ONFH) induced by liquid nitrogen freezing in rabbits and
      discuss the mechanism for preventing and treating ONFH. METHOD: The ONFH model
      was established by liquid nitrogen freezing of 84 rabbits. They were randomly
      assigned to the model group and the Huogu II formula group and groups of Huogu II
      formula combining with Achyranthis Bidentatae Radix, Asari Radix et Rhizoma,
      Angelicae Pubescentis Radix, Platycodonis Radix. The remaining 14 rabbits were
      sham-operated. During the course of ONFH modeling, all of the rabbits were
      subcutaneously injected with recombinant human granulocyte colony-stimulating
      factor (rhG-CSF)(30 microg x kg(-1) x d(-1), for consecutively 7 days).
      Meanwhile, normal saline and decoction of the formulae were orally administrated
      respectively. WBC was counted in peripheral blood before and after the injection
      of rhG-CSF. HE stainings at the 2nd and the 4th weeks after the modeling were
      adopted to observe histopathological changes, vascular morphology was observed by
      ink perfusion, BrdU and SDF-1 were determined by immunohistochemical assay in
      femoral heads of the left hind leg. RESULT: Compared with the sham-operated
      group, the Huogu II formula group showed decrease in the ratio of empty lacuna
      and increase in vessel area, number of BrdU positive cells and SDF-1 level. In
      comparison with the model group, the Achyranthis Bidentatae Radix group displayed
      decreasing empty lacuna ratio and increasing vessel area at the 4th week and
      increasing SDF-1 at the 2nd week; the Platycodonis Radix group revealed a notably
      increasing empty lacuna ratio and a sharp decrease in the number of BrdU positive
      cells at 4th week; Asari Radix et Rhizoma and Angelicae Dubescentis Radix groups
      showed no remarkable change. CONCLUSION: Huogu II formula can promote the
      directional homing of bone marrow stem cell to the necrosis area. Channel
      ushering drug achyranthes can further boost above effects of Huogu II formula.

PMID- 22993996
TI  - [Analysis on establishment and affecting factors of qi stagnation and blood
      stasis rat model].
AB  - OBJECTIVE: To study on the method for establishing the Qi stagnation and blood
      stasis rat model and analyze the affecting factors. METHOD: The orthogonal design
      was adopted to study the influences of joint stimulations including noise, light,
      electricity, ice water bath, tail-clamping on model rats. The 'flying spot'
      method was used to dynamically simulate blood flow velocity in microcirculation.
      the pressure sensing technology of MOTO was adopted to detect hemorheology
      related indicators. And the coagulation method was used to detect blood
      coagulation-related indicators. RESULT: Compared with the negative control group,
      all model groups showed significant reduction in the blood flow velocity in
      mesenteric microcirculation and increase in the whole blood viscosity at high,
      medium and low shear rate, the plasma viscosity and the fibrinogen content in
      four blood coagulation indicators. CONCLUSION: Noise, light, electricity, tail
      clamping, bondage and icewater-bath make significant impact on model rats.

PMID- 22993997
TI  - [Effects of guizhi tang on inflammatory cytokines in myocardial ischemia and
      hyperlipidemia rats].
AB  - OBJECTIVE: To explore the effects of Guizhi Tang on the inflammatory cytokines in
      myocardial ischemia and hyperlipidemia rats. METHOD: The early changes of
      hyperlipid and atherosclerosis are caused by utilizing multiple factors including
      feeding hyperlipid and propylthiouracil and high doses of vitamin D3 for 12
      weeks. Sixty male SD rats were randomly divided in to 5 groups: control group,
      model group, simvastatin group, low-dosage Guizhi Tang group, high-dosage Guizhi
      Tang group. At the end of six weeks treatment, pituitrin(pit) is abdominal cavity
      injected every 24 hours for a total of three times. Detecting the serum levels of
      SES, CRP, NO, SOD, MDA and the content of cardiac muscle tissue SOD, MDA, The
      expression of TNF-alpha in cardiac muscle tissue was detected by
      immunohistochemistry. RESULT: Guizhi Tang significantly decreased levels of SES,
      CRP and MAD, increased levels of NO and SOD, Guizhi Tang markedly decreased the
      level of protein expression of TNF-alpha in cardiac muscle tissue. CONCLUSION:
      Guizhi Tang may inhibit the proinflammatory factors and oxidation in myocardial
      ischemia and hyperlipidemia rats.

PMID- 22993998
TI  - [Study on regulatory effect of Kaixin San on endogenous melatonin biosynthesis in
      rat depression model].
AB  - OBJECTIVE: To study the effect of Kaixin San on the rate-limiting enzyme in
      biosynthesis of melatonin (MT) and pineal body in rat depression model. METHOD:
      The unpredictable chronic mild stress was used to establish the rat depression
      model for 21 days. The rats were divided into the normal control group, the model
      group, Kaixin San low, medium and high dose groups (KXS 65, 130, 260 mg x kg x d(
      1)) and the trazodone group. All groups were administered at 30 min after
      modeling each day. Rats were sacrificed and the pineal glands were isolated
      immediately after acquisition tail venous blood at 2:00a. m on the 22nd day. The
      plasma was analyzed for melatonin content by using a rat metabolic panel
      Milliplex kit. The pineal glands were analyzed for AANAT and HIOMT mRNA levels by
      Real-time quantitative PCR and for AANAT and HIOMT activity by a radiometric
      assay simultaneously. RESULT: The plasma MT concentration, expression of AANT and
      HIOMT mRNA, activity of AANAT in rat pineal glands of the model group were
      significantly lower than the control group (P < 0.05), but the activity of HIOMT
      showed not change. Compared with the model group, all of Kaixin San groups showed
      increase in MT concentration in plasma (P <0. 05) , with the medium dose group
      revealing the highest level. Besides, the medium dose group displayed significant
      increase in AANAT, HIOMT mRNA level and AANAT activity (P < 0.05), but no
      increase in HIOMT activity. CONCLUSION: Kaixin San can regulate AANAT activity of
      pineal bodyand regulate MT biosynthesis in rat depression model.

PMID- 22993999
TI  - [Effect and mechanism of Saururus chinensis against herpes dimplex virus].
AB  - OBJECTIVE: To seek effective drugs inhibiting herpes simplex virus (HSV-2) with
      the signal pathway required by virus replication as the target spot. METHOD: HSV
      2-induced Vero cytopathic effect was observed, and MTT method was adopted to
      detect call activity, in order to assess the antiviral capacity of freeze dried
      powder of aqueous extracts of Saururus chinensis (AESC). Western blot was used to
      check the effect of AESC on signal pathway induced by HSV-2 virus in HeLa cells.
      RESULT: AESC obviously inhibits the pathway activation of CPE induced by HSV-2
      infection and NF-kappaB required for virus replication. The inhibition ratio of
      AESC freeze dried powder at 0.10, 0.03, 0.01 and 0.003 g x L(-1) were (70.68 +/-
      3.39)%, (61.74 +/- 2.13)%, (39.31 +/- 1.10)% and (18.54 +/- 3.44)%, respectively.
      The IC50 was determined at (0.023 +/- 0.004) g x L(-1). The inhibition
      concentration of the positive control acyclovir was 0.001 g x L(-1) (5.0 x 10(-6)
      mol x L(-1)). The best administration time was from 2 h before infection to 6 h
      after infection. Western blot also showed that AESC can notably inhibit HSV-2
      induced NF-kappaB nuclear transfer. CONCLUSION: AESC can inhibit HSV-2 virus
      replication, which is related to the pathway activation of NF-kappaB required for
      virus replication.

PMID- 22994000
TI  - [Estrogen-like effects of Menoprogen on female ovariectomized rats].
AB  - OBJECTIVE: To study the estrogen-like action mechanism of Menoprogen on
      ovariectomized female rats. METHOD: Ovariectomized rat model (OVX) was
      established and estradiol (17beta-estradiol, E2) was used as positive control.
      The uterine coefficient and serum E2 level were determined after administration
      of Menoprogen for 2 weeks. The uterine vascular endothelial growth factor (VEGF),
      water channel protein (aquaporin, AQP), estrogen receptor (ER), progesterone
      receptor (PR) and the expression of proto-oncogenes (c-jun, c-fos) were observed
      by immunohistochemical method. Yeast two-hybrid assay was applied to detect the
      existence of components combining with ERalpha or ERbeta in Menoprogen. RESULT:
      Both Menoprogen and E2 could significantly elevate the uterine coefficient of OVX
      rats, increase the level of serum E2 and up-regulate the expressions of VEGF,
      AQP2 as well as AQP5 in uterus. E2, not as E2 Menoprogen couldn't promote the
      expressions of ERalpha, PR, c-jun and c-fos in OVX rat uterus. And yeast two
      hybrid assay showed no components combining with ERalpha or ERbeta in Menoprogen.
      CONCLUSION: Menoprogen has estrogen-like effect, and can be used to treat
      menopause syndrome. The risk of estrogen-mediated endometrial cancer is low for
      this treatment because its mechanism is different from estrogen-like substances.

PMID- 22994001
TI  - [Study on anti-tumor effect of cyanidin-3-glucoside on ovarian cancer].
AB  - OBJECTIVE: To investigate the effect and the mechanism of cyanidin-3-glucoside
      (C3G) in the growth inhibition of ovarian cancer in vitro and in vivo. METHOD:
      After human ovarian cancer cell line HO-8910PM was treated with C3G, cell growth
      was determined by the Cell Counting Kit-8 (CCK-8) assay and apoptosis was
      evaluated by flow cytometry analysis stained with Annexin V-FITC/PI. The protein
      expression in HO-8910PM cells was analyzed by Western blot assay. HO-8910PM cells
      were injected subcutaneously into nude mice to establish xenograft model. After 3
      weeks of implantation, mice were randomized into 2 groups (n = 8): control group,
      feed with 0.2 mL double distilled water; C3G group, feed with C3G at a dose of 5
      mg x kg(-1). All treatment lasted for two weeks, thrice per week. Eight weeks
      after implantation, tumor weight and inhibition rate were evaluated respectively
      after the mice were sacrificed. Immunohistochemistry was used to detect the
      positive expression of Ki-67 and Mucin-4 in the tumors. RESULT: The proliferation
      of ovarian cancer cells was inhibited significantly by C3G with IC50 being 13.82
      mg x L(-1). Apoptosis rate induced by C3G was markedly highter than that of
      control. The expression of Mucin4 was down-regulated in HO-8910PM cells after
      treatment of C3G. C3G inhibited the growth of ovarian xenograft tumors in nude
      mice. Furthermore, the positive expression of Ki-67 and Mucin-4 were both
      decreased in tumors after administration of C3G. CONCLUSION: C3G exerts anti
      tumor activity in ovarian cancer both in vitro and in vivo, which may be related
      to down-regulation of Mucin-4 protein.

PMID- 22994003
TI  - [Experimental study on effect of Salvia miltiorrhiza on alveolar bone metabolism
      and variation in bone mass in diabetic rats].
AB  - OBJECTIVE: To study the effect of Salvia miltiorrhiza on alveolar bone metabolism
      and variation in bone mass in diabetic rats, in order to detect whether it has an
      inhibitory effect on alveolar bone osteoporosis caused by diabetics. METHOD:
      Intraperitoneal injection of alloxan induced diabetes in rats. After one week of
      observation and maintenance of stable blood sugar level, they were treated with
      S. miltiorrhiza. The rats were sacrificed at the eighth week after fasting for 12
      h and blood samples were collected for analysis of blood glucose and rate of bone
      metabolism. Meanwhile, their alveolar bones were collected for determining bone
      mineral density (BMD) and histological sections were made for histomorphology
      observation. RESULT: Diabetic rats showed varying degrees of abnormality in bone
      metabolism indicators and significant reduction in bone mineral density. After
      treatment with S. miltiorrhiza, their symptoms reduced to some extend and all
      indicators were improved especially bone density. CONCLUSION: S. miltiorrhiza has
      a certain inhibitory effect on alveolar bone osteoporosis in diabetic rats in
      early stage.

PMID- 22994002
TI  - [Expression of inducible nitric oxide synthase in restenosis rats and function of
      Astragalus membranaceus and Angelica sinensis].
AB  - OBJECTIVE: To explore the expression of inducible nitric oxide synthase (iNOS) in
      restenosis rats and function of Astragalus membranaceus and Angelica sinensis.
      METHOD: The restenosis model was established by denuding aorta endothelium, rats
      were randomly divided into control group, model group, A. membranaceus treatment
      group, A. sinensis treatment group, combined A. membranaceus with A. sinensis
      treatment group. After intramuscular injection of drugs for 21 dayss, the changes
      of iNOS in restenosis rats were observed by histomorphology and
      immunohistochemisty, the effects of A. membranaceus and A. sinensis on iNOS in
      restenosis rats was also investigated. RESULT: A small quantity of iNOS were
      detected in the intima and media of normal aorta, the expression of iNOS was
      increased on 3 day after denuding aorta endothelium, the expression of iNOS
      increasd and the color darken along with injury damage and intima thickening.
      Compared with model group, the expression of iNOS decreasd in A. membranaceus, A.
      sinensis treated group, A. membranaceus and A. sinensis treated group changed
      more significantly. CONCLUSION: iNOS was involved in blood vessel restenosis by
      denuding aorta endothelium, A. membranaceus, A. sinensis could inhibit intimal
      proliferation through iNOS.

PMID- 22994004
TI  - [Effect of pine pollen on kidney mitochondria DNA deletion mutation in senile
      mice].
AB  - OBJECTIVE: To study the effect of pine pollen on Kidney Mitochondria DNA Deletion
      Mutation (mtDNA) in senile mice. METHOD: Kunming senile mice were randomly
      divided into the pine pollen group, and the senile control group. And a young
      control group was randomly selected. Mouse in the pine pollen group were orally
      administered with pine pollen (750 mg x kg(-1)) daily. The young control group
      and the senile control group were orally administered with isometric 0.9% sodium
      chloride injection. After 60 days, deletion mutation of mtDNA were detected by
      PCR technology and photodensity scan. Relative level of MDA and activity of SOD
      in kidney tissues were detected. RESULT: The senile control group showed
      significant increase in relative level and deletion mutation of mtDNA (P < 0.05).
      Compared with the senile control group, the pine pollen group showed decreased
      depletion of kidney mtDNA (P < 0.05). Pine pollen can decrease MDA volume and
      increase the activity of SOD significantly (P < 0.05). CONCLUSION: Pine pollen
      can inhibit deletion mutation of mtDNA in senile mice, suggesting that pine
      pollen can reduce oxidative damage of mtDNA and protect mtDNA. Accordingly, it
      provides a possible mechanism of anti-aging effect of pine pollen at the
      molecular level.

PMID- 22994005
TI  - [Study on detoxication of kansui radix on normal liver cells LO2 after stir
      baking with vinegar].
AB  - OBJECTIVE: To compare the toxicity on normal liver cells LO2 before and after
      Kansui Radix stir-baked with vinegar, and make a preliminary study on the
      mechanism of detoxication of Kansui Radix stir-baked with vinegar. METHOD: The
      MTT method was adopted to detect the cell activity, with normal liver cells LO2
      as the study object. The morphology of cells were observed, and the level or
      content of AST, ALT, LDH, SOD, Na+-K+-ATPase, Ca2+-Mg2+ -ATPase, GSH and MDA were
      determined in cell culture supernatant and splitting supernatant. RESULT:
      Compared with the control group, Kansui can obviously inhibit the cell activity
      (P < 0.01) and morphology, and increase the levels of ALT, AST, and LDH (P <
      0.01) in the supernatant fluid of cell incubation, and decrease the level of SOD
      and the content of GSH (P < 0.01). Besides, it significantly increased the
      content of MDA (P < 0.01) and significantly decreased the level of Na+-K+-ATPase
      and Ca2+-Mg2+ -ATPase (P < 0.01) in the supernatant fluid of cell dissociation.
      Compared with Kansui group of various doses, Kansui Radix stir-baked with vinegar
      can significantly decrease the cell proliferation inhibition and the trend of
      morphological variation, and obviously decrease the levels of ALT, AST, and LDH
      (P < 0.01) in the supernatant fluid of cell incubation, and significantly
      increase the level of SOD and the content of GSH (P < 0.01), and significantly
      decrease the content of MDA (P < 0.01). Additionally, it significantly increased
      the level of Na+-K+-ATPase and Ca2+-Mg2+ ATPase (P < 0.01) in the supernatant
      fluid of cell dissociation, and showed a certain dose-effect relationship.
      CONCLUSION: Stir-baking with rice vinegar can release the hepatotoxicity of
      Kansui Radix. Its possible mechanism was that Kansui Radix stir-baked with
      vinegar can decrease the influence of Kansui Radix on the permeability of liver
      cells LO2 membrane and oxidative damage, in order to provide basis for further
      exploration of the detoxication mechanism of Kansui Radix stir-baked with
      vinegar.

PMID- 22994006
TI  - [Study on in vitro and in vivo material base of Sini San by UPLC-PDA-MS/MS].
AB  - OBJECTIVE: To analyze chemical constituents of Sini San its migrating components
      in rat plasma and study its in vitro and in vivo material base using ultra
      performance liquid chromatography coupled with photo-diode-array detector and
      tandem mass spetrometry (UPLC-PDA-MS/MS). METHOD: ACQUITY UPLC BEH C18 column
      (2.1 mm x 100 mm, 1.7 microm) was adopted, with gradient elution system of water
      containing 2 mmol x L(-1) ammonium acetate and acetonitrile at flow rate of 0.2
      mL x min(-1). The column temperature was maintained at 35 degrees C. The mass
      spectra were obtained by electrospray ionization source operating in both
      positive and negative ion mode. Ions were scanned from the m/z 100 to 1 000, and
      the characteristic ions were schizolysised twice to obtain the secondary MS data.
      RESULT: Twenty chemical constituents were detected, including paeoniflorin,
      glycyrrhizic acid, saikosaponins a and naringin. In vivo, there were 8
      ingredients directly absorbed into blood after the administration of Sini San
      decoction, such as paeoniflorin, naringin and hesperidin. Besides, 6 metabolites
      were also detected, involving glucuronides, sulfate and sulfoglucuronides.
      CONCLUSION: In vitro and in vivo chemical materials of Sini San decoction is
      analyzed by UPLC-PDA-MS/MS to reflect in vitro and in vivo material base of Sini
      San decoction in a comprehensive and rapid manner and provide basis for further
      study on efficacious material basis of Sini San decoction.

PMID- 22994007
TI  - [Distribution of puerarin contained in Zige freeze-dried powder injection in rat
      liver and kidney].
AB  - OBJECTIVE: To investigate the distribution process of puerarin contained in Zige
      freeze-dried powder injection in rat liver and kidney and the safety of Zige
      freeze-dried powder injection. METHOD: Rats were divided into the Zige freeze
      dried powder injection group and the puerarin freeze-dried powder injection
      control group randomly. The liver and kidney samples were collected at 5, 10, 20,
      30, 45, 60 and 120 min after intravenous administration of puerarin (26.7 microg
      x g(-1)) through caudal vein and detected by HPLC. RESULT: The concentration of
      puerarin in kidney reached the max value of 58.12 microg x g(-1) for the Zige
      freeze-dried powder injection group and 71.28 microg x g(-1) for the Puerarin
      freeze-dried powder injection group. The value of AUC(0-2h) was 26.24 microg x h
      x g(-1) for the Zige freeze-dried powder injection group and 35.24 microg x h x
      g(-1) for the puerarin freeze-dried powder injection group, MRT(0-2h) was 0. 39 h
      for the Zige freeze-dried powder injection group and 0. 42 h for the puerarin
      freeze-dried powder injection control group. Compared with the control group, the
      Zige freeze-dried powder injection group showed a significant decrease in Cmax
      and AUC(0-2h) (P < 0.05), with no notable difference in peak time tmax and MRT(0
      2h). The two groups showed no obvious difference in tmax Cmax, AUC(0-2h) and
      MRT(0-2h) of puerarin in rat kidney. CONCLUSION: Compared with Zige freeze-dried
      powder injection, Zige freeze-dried powder injection can reduce the distribution
      of puerarin in rat kidney, with no obvious change in the elimination of puerarin
      in rat kidney. It also showed no significant change in distribution and
      elimination in liver. This indicates that Zige freeze-dried powder injection is
      safer to kidney than puerarin freeze-dried powder injection.

PMID- 22994008
TI  - [Metabonomic study of intervention effects of Morinda officinalis on 'kidney-yang
      deficiency syndrome'].
AB  - OBJECTIVE: To investigate the metabolic profile of hydrocortisone-induced 'Kidney
      yang deficiency syndrome'in rats and the intervention effects of Morinda
      officinalis. METHOD: Proton nuclear magnetic resonance (1H-NMR) technique was
      used to analyze the rat metabonome in serum. Orthogonal partial least squares
      discriminant analysis (OPLS-DA) were processed to analyze the metabonome
      difference between the control and hydrocortisone treated samples. Twelve
      potential biomarkers were selected, via the parameter of variable importance in
      the projection (VIP). Principal components analysis (PCA) was employed to process
      the data from the M. officinalis. treatment group and the intervention effects of
      M. officinalis, was investigated through the selected potential biomarkers.
      RESULT: After hydrocortisone treatment, the energy metabolism, amino acids
      metabolism and gut microflora environment were seriously disturbed and
      transmethylation was surpressed. M. officinalis could effectively alleviate the
      disturbance of energy and amino acids metabolism and enhance transmethylation,
      but could not modulate the gut microflora environment. CONCLUSION: The results
      obtained suggested that metabonomic studies could better reflect the whole status
      of metabolism in bio-systems, and could be treated as a potential powerful
      approach in pharmacological studies and investigation of the essence of
      'syndrome' in traditional Chinese medicine.

PMID- 22994009
TI  - [New bencaological studies of traditional Chinese medicine after name "doukou"].
AB  - Lots of traditional Chinese medicine (TCM) shares the same Chinese common names
      "Doukou". Because of similar Chinese names, appearances, functions and original
      plants, there are still no compromise on the original plants of "Doukou" up to
      now. Moreover, "Doukou" referred to more than one source of species, that is, it
      might refer to the Chinese crude drug derived from different plants during
      different historical periods. In order to identify the original botanical plants
      of "Doukou" during different historical periods and the relationship between
      these "Doukou", new bencaological studies of TCM under the name "Doukou" were
      carried out, which included the studies on literal description, image
      description, market investigation and systematic botanical research. A suggestion
      was made to change the Chinese name "Doukou" (Amomi Fructus Rotundus) to
      "Baidoukou".

PMID- 22994010
TI  - [Pathophysiological mechanisms of allergic disease occurrence and treatment].
AB  - Why the exposure to the harmless and ubiquitous environmental substances causes
      inappropriately strong reactions of the immune system clinically manifested as
      allergies in some people, and how repeated exposures to the same substances
      during the specific immunotherapy divert immunologic reactivity, are so far only
      partially answered questions. The events that occur during the allergic
      inflammatory response are relatively well-known, as are the major operative
      mechanisms through which the specific immunotherapy, the only causative treatment
      method, changes that response. Nevertheless, everyday new findings are completing
      the puzzle and our understanding of these complex processes. The aim of this
      paper was to review the up-to-date known mechanisms of allergic disease
      occurrence and treatment, with regard to the key role of T cells in these
      processes.

PMID- 22994011
TI  - [New vaccination protocol against hepatitis B for hemodialysis patients--a single
      centre experience].
AB  - Patients with end stage renal disease (ESRD) have a reduced response to
      vaccination against hepatitis B infection. The aim of the study has been to
      determine the adequacy of immune response with new protocol of vaccination
      against hepatitis B infection. PATIENTS AND METHODS: The study included incident
      hemodialysis patients since 2008 until 2011 at the Clinic of Hemodialysis of the
      Clinical Center of the University of Sarajevo. We started the new vaccination
      protocol in September 2009. New protocol implied vaccination six month before
      starting renal replacement therapy (RRT) and "ic" (intracutaneously) application
      vaccine vs. "sc" (subcutaneously) application. Vaccination was carried out for
      over 12 months. The follow up period lasted from 2009 to 2011. RESULTS: The study
      included 64 patients, men were represented with 57,81% (37), and 42,19% women
      (27), who were divided in two groups. The first group included patients from the
      period from 2008 to 2009, who have been vaccinated under the old vaccination
      protocol, while the second group included patients with the new protocol from
      September 2009 to 2011. The first group had 28 patients, mean age of patients was
      55,17 +/- 11.84 and mean duration of hemodialysis was 24,65 +/- 5,32 months. The
      second group had 36 patients, mean age of patients was 62,79 +/- 15,88 years, and
      mean duration of hemodialysis was 22,16 +/- 24,53 month. Neither group of patient
      has been previously vaccinated, nor these had positive in serum antiHBs before
      vaccination in second group. Five patients received a booster dose of vaccine,
      after which 4 showed adequate responses to anti HbS. In the first group of
      patients, out of total of 28 patients, 15 patients did not respond response with
      the adequate anti-HbS titer at the end of vaccination. In the second group of
      patients, out of 36 patients 31 of them responded to the vaccination with the new
      protocol, which was statistically significant (p<0,005). The total percentage of
      patients with adequate titer of antiHBs after vaccination towards a new protocol
      was 97.43% and the percentage of patients who required booster dose of vaccines
      was 12.82%. CONCLUSION: Vaccination of patients in ESRD,six months before renal
      replacement therapy and intradermal application of vaccine vs. subcutaneously,
      improved immune response of our patients.

PMID- 22994012
TI  - [Use of music in palliative care].
AB  - Man is mortal, which means that as the earthly body perishes being, final.
      Disease and death will always be an inevitable and integral part of human
      experience. The way in which we try to identify and respond to the unique and
      individual needs of the dying is an indication of our maturity as a society. The
      number of people requiring palliative care is growing. Palliative care does not
      intend to either accelerate or postpone death she emphasizes the life and looks
      at dying as a normal process. It is an active form of care for patients with
      advanced, progressive illness, with the aim of suppressing pain and other
      symptoms in addition to providing psychological, social and spiritual support
      which ensures the best possible quality of life for patients and their families.
      Therefore requires a coordinated and interdisciplinary contribution team. The
      variety of professions in a team, and determine the needs of patients should be
      ready to provide physical, psychological, social and spiritual support using
      methods that result from an interdisciplinary, collaborative team approach.
      Development of a holistic approach and awareness in the medical and allied
      professions has led to a renewal of interest in the inclusion of music and other
      expressive media in contemporary concepts of palliative care, which are
      consistent with problem areas, clinical manifestations and the needs of patients.
      Music offers a direct and uncomplicated medium of intimacy, living in a man who
      listens to her, has a place where words lose their power. Music is like our
      existence, constantly polarizing and emotionally stimulating, as it touches the
      medium of the earliest layers of our becoming. The use of music in palliative
      care has proved very effective for a variety of effects that music creates in
      patients. These effects are achieved through the use of various musical
      techniques, such as musical improvisation, songwriting, receiving creative
      techniques, guided by imagination and music. These techniques allow the diversity
      of objectives in treating patients such as reducing anxiety and stress,
      relaxation, pain control, reducing confusion spiritual, emotional expression,
      experience, self-awareness, encourage creative expression, causing mood swings -
      emotional, cognitive and behavioral, inducing the patient's imagination, enabling
      patient's chronological classification of life experiences, and the elaboration
      of unresolved pain, sorrow or errors. Adequate selection and use of musical
      techniques in palliative care in the service of achieving the best possible
      quality of life for patients at the end of life.

PMID- 22994013
TI  - [The high-affinity IgE-receptor signaling pathway in the treatment of allergies].
AB  - The rise in a prevalence of allergic diseases observed in industrialized
      countries over many years, and generally a rising number of the patients, require
      constant searching for newer and better ways of treatment. The central event in
      the formation of the allergic inflammation, the activation of mast cells and
      basophils, is mediated by signaling through the high-affinity IgE receptor,
      FcepsilonRI. The signaling starts by cross-linking of receptor-bound IgE with an
      allergen. This initiates a cascade of signaling events that activates the cell
      and ultimately causes the release of mediators responsible for allergic
      responses. The major flaw of medications traditionally used for the treatment of
      allergies is their orientation to single mediators, and not to the whole sequence
      of complex events leading to the onset of early and late symptoms. The aim of
      this paper was to review a complex sequence of events from the allergen binding
      to the onset of symptoms, highlighting the importance of the IgE-receptor
      signaling pathway in searching for new therapeutic modalities.

PMID- 22994014
TI  - [Acute compartment syndrome as a complication of prolonged surgery in the Lloyd
      Davies position].
AB  - Acute compartment syndrome of the muscle is condition in which prolonged increase
      of tissue pressure in closed unyelding fascial compartments reduces capillary
      perfusion below a level necessary for tissue viability leading to muscle and
      nerve ischaemia for few hours. There are wide variety different clinical settings
      associated with compartment syndrome. Acute lower limb compartment syndrome that
      occur during and after prolonged surgical procedures in Lloyd Davies position is
      rare but potentially devastating complication that can lead serious local
      complications and life threatening situations as, rabdomyolysis, kidney failure
      and death. In this article we summarize pathophysiology, clinical staging and
      diagnostic procedures of acute compartment syndrome in Lloyd Davies position. We
      present female patient developed limb compartment sindrome after surgical
      procedure which lasted 6,5 hours in the Lloyd Davies position for extensive
      rectovaginal endometriosis. In this article we rewiev different contributing
      factors that may predispose to compartment syndrome during Lloyd Davies position
      and undescore importance of recognise the risk factor and prevent the
      esthablishment of acute compartment syndrome during and after surgery in the
      Lloyd Davies position.

PMID- 22994015
TI  - [Hospitalization of children with traumatic brain wounds in Brodposavina county].
AB  - Traumatic brain injury (TBI) is the most common cause of acquired disability and
      death in children. Retrospective analysis showed 350 children, 128 (36.6%) girls
      and 222 (63.4%) boys who were hospitalized for injury of neurocranium in a 5 year
      period in Dr. Josip Bencevic General Hospital in Slavonski Brod. Most of them had
      both contusion and commotion (46.8%), followed by just contusion of the head
      (12.5%) and fractures of the skull (10.5%). The haemorrhages and hemathomas were
      less common (epidural, subdural, SAH) (3.2%). The procedures performed showed
      that in almost all children X-rays had been performed (99.7%). The most commonly
      X-rays performed were those of the head (craniogram) and/or cervical spine,
      followed by CT, EEG, ultrasound and NMR. The occurence of complications was
      recorded in only 2% of injured children (seizure, syncopa, febrile convulsions).
      Analysis of treatment methods showed that in most children (89.6%) therapy was
      conservative. The injured children were hospitalizated mostly for 2 days (34.5%)
      or 3 days (32.5%), while longer hospitalization was less common. Regarding extra
      consultation of other specialists (besides neurosurgeons), the most commonly
      consulted were pediatrician, surgeon/traumatologist, specialist of
      ENT/maxilofacial surgery, neuropediatrician, pediatric surgeon, ophthalmologist
      and others. It can be said that the prognosis of TBI in children depends on the
      age, neurological status and kind of injury, and on the quality of care, which
      involves availability of neurosurgeons and other specialists.

PMID- 22994016
TI  - [100 years of Hashimoto thyroiditis, still an intriguing disease].
AB  - INTRODUCTION: In 1912 Japanese physician Hashimoto Hakaru described 4 patients
      with chronic thyroid disease. The histopathology findings exactly 100 years ago
      described lymphocyte infiltration, fibrosis, parenchymal atrophy and eosinophilic
      changes of some acinar cells. Those findings are typical for the autoimmune
      thyroid disease named by the author Hashimoto thyroiditis or lymphocytic
      thyroiditis. Hashimoto thyroiditis: The pathophysiology of thyroid autoimmunity
      during the past decades was described in details. Many thyroid antigens were
      identified (thyroid - stimulating hormone or TSH, thyroglobulin,
      thyreoperoxidase) and antibodies are directed towards them. Thyreocyte is also
      able to function as antigen presenting cell. It presents antigen on its surface
      and expresses MHC class II and class I molecules. Etiology of autoimmune
      thyroiditis combines genetic and environmental factors. Genetic factors dominate,
      and influence with about 80% on the occurrence of immunity. Some HLA genes (HLA
      DR3, HLA-DR4, HLA-DR5 and HLA-DQA) and some non-HLA genes (cytotoxic T-lymphocyte
      antigen 4 -CTLA-4, CD40 gene, gene for protein tyrosine phosphatase 22 -PTPN22,
      thyroglobulin and TSH gene) are involved. 20% of etiology is attributed to
      environmental factors (smoking, iodine intake, selenium deficiency, pollution,
      infectious conditions, physical and emotional stress) and physiological states
      (puberty, rapid growth, pregnancy, menopause, aging, female gender). Although
      Hashimoto thyroiditis is known for many years, it is still sometimes presented
      with surprisingly diverse clinical entities and frequently astonishes many
      physicians. CASE REPORT: A case of a female patient with long-standing hypothesis
      (fine needle aspiration showed lymphocytic infiltration, thyreoperoxidase
      antibodies were positive) is presented. During the postpartum period, complicated
      with septic endometritis a new onset of hyperthyreosis appeared. The etiology of
      hyperthyroidism was unclear, with three possible explanations. The first one was
      that residual placental mass could cause prolonged exposure to beta- HCG. Beta-
      HCG causes hyperthyroidism mimicking action of TSH. The second explanation was
      that sepsis changes the nature of antibodies directed to the TSH receptor -
      thyrotrophin binding inhibitory antibodies become thyroid stimulating antibodies.
      The last explanation pointed to the pregnancy as a trigger itself that influenced
      on the immune events. Hyperthyreosis was followed by hypothyreosis and
      substitution with previous dosage of levothyroxine was continued. The answer of
      the sudden hyperthyreosis was given in subsequent pregnancy that happened 2,5
      years later. The following one was free of complications, but postpartum
      hyperthyroidism occurred again. Further course of disease suited to lymphocytic
      thyroiditis with hypothyroidism, and she is substituted with levothyroxine until
      now. DISCUSSION: During normal pregnancy it is expected to have decreased ratio
      of CD4+/CD8+ lymphocyte subpopulation. Studies showed that women who developed
      postpartum thyroiditis had a higher ratio of CD4+/CD8+ and they were generally
      anti-TPO positive. It is considered that the lack of the expected suppression of
      immune function during pregnancy leads to postpartum thyroiditis. In this case
      Hashimoto thyroiditis showed two different faces: it was presented with long term
      hypothyroidism, but in postpartum period it converted to hyperthyroidism - a
      typical picture of postpartum thyroiditis. CONCLUSION: Pregnancy as a trigger can
      reveal till then unrecognized autoimmune disorder, or modify its course from
      hypothyroidism to hyperthyroidism. Hashimoto disease even 100 years after the
      discovery may surprise with one of its many faces.

PMID- 22994017
TI  - ["Returning to the Sun" of Antun Branko Simic].
AB  - Antun Branko Simic, one of the greatest Croatian poets, died very young, at the
      age of 27, from tuberculosis. The history of his disease has not been
      reconstructed for eight decades although that could also open a more accurate
      view on his literary work. By uncovering the original documents, his disease and
      death could be positioned in historical, social and cultural context. It was
      shown that those who emphasized the crucial impact of disease on his entire
      literary work were wrong. No doubt that A. B. Simic has written under the
      influence of his disease but that can refer only to the small number of poems and
      essays. First of all he wrote in line with world poetry of his time-
      expressionism, which was significantly inspired by patients' and social
      sufferings.

PMID- 22994018
TI  - Attitude and preference of Thai pregnant women towards mode of delivery.
AB  - OBJECTIVE: To explore the attitudes and wishes of Thai pregnant women regarding
      modes of delivery. MATERIAL AND METHOD: Four hundred fifteen pregnant women
      attending the Vajira Hospital antenatal clinic were included in the present
      study. Data was assembled from the voluntarily self-completion questionnaires
      completed by the eligible women. RESULTS: Only 3.1% of the participants could
      give entirely correct answers in the knowledge module. Most of the respondents
      (87.5%) preferred vaginal delivery. The most popular reason for the preference
      for vaginal delivery was desire for a natural process. Fear of labor pain was the
      most frequent reason of the women who preferred cesarean section. The strongest
      predictor for patients' preference for cesarean delivery was a prior cesarean
      section (RR 11.1, 95% CI 4.7 to 26). Thirty-two percent of the participants felt
      that cesarean delivery on maternal request was their right and they desired to
      take part in the decision-making for their mode of delivery. Of those women who
      stated that cesarean section on demand was their right, the majority (77.3%)
      still preferred vaginal delivery. CONCLUSION: Although the proportion of Thai
      pregnant women who wished to have a cesarean delivery was higher than that of
      women from other countries, the majority of study participants preferred vaginal
      delivery.

PMID- 22994019
TI  - Comparison of condition specific indicators among illegal induced abortion:
      septic and non-septic abortion in Songkla Center Hospital.
AB  - OBJECTIVE: Determine the clinical indications of illegal induced abortion,
      comparison between septic and non-septic abortion. MATERIAL AND METHOD: The
      present retrospective descriptive study was conducted among pregnant women who
      were admitted in the hospital with the illegal induced abortion. The demographic
      data, gestational age, the method used, and personnel performing were gathered,
      as well as symptomatology, basic laboratory, condition progression, and medical
      and surgical intervention. RESULTS: There were 92 patients with illegal induced
      abortion between March 2009 and December 2010. The three main induced methods for
      termination of pregnancy was vaginal suppository, likely to be misoprostol-a
      synthetic prostaglandin E, analog (43.5%), oral Thai herbal medicine (19.6%) and
      combined medication (16.3%), respectively. Of septic/non-septic abortion, the
      first visit body temperature of 38.0 degrees Celsius or more (74.1/12.3%), heart
      rate of 100 per minutes or more (74.1/12.3%), fever index 3 degree-hours or more
      in the first 24 hours (81.5/12.3%) and fever index 5 degree-hours or more in the
      first 24 hours (59.3/1.5%), were statistically significant (all p-values of <
      0.001). Overall, the most common type of termination of induced abortion was
      incomplete abortion 68 in 92 cases (73.9%). CONCLUSION: The first visit body
      temperature of 38.0 degrees C or more, heart rate of 100 per minutes or more and
      fever index of 3 and 5 degree-hours, are clinically helpful in the early
      diagnosis and treatment of septic abortion.

PMID- 22994020
TI  - Cycle control, safety and acceptability of a new oral contraceptive containing
      ethinylestradiol 15 micrograms and gestodene 60 micrograms.
AB  - OBJECTIVE: To determine cycle control, safety, and acceptability of a 24-day oral
      contraceptive regimen containing 15 micrograms of ethinylestradiol and 60
      micrograms of gestodene. MATERIAL AND METHOD: This was an open-label, non
      comparative study. Healthy women 18 to 35 years old who attended the Family
      Planning Clinic of King Chulalongkorn Memorial Hospital were assigned to receive
      six cycles of the study oral contraceptives, administered daily for 24 days and
      followed by a 4-day hormone-free interval. Data on bleeding patterns, side
      effects, body weight, blood pressure, and satisfaction were collected.
      Descriptive statistics and paired t test were used for the analysis. RESULTS:
      Ninety-four women completed the present study. There was no pregnancy reported
      during the present study. Percentages of breakthrough bleeding and spotting were
      higher in the first cycle (2.1% and 6.4%), then decreased and disappeared after
      the third cycle. There was no significant change in the body weight and the blood
      pressure. Only minimal side effects were reported and 93.6% of the women were
      satisfied or very satisfied. Furthermore, 91.5% would continue using this oral
      contraceptive. CONCLUSION: This new oral contraceptive, a combination of 15
      micrograms of ethinylestradiol and 60 micrograms of gestodene has acceptable
      cycle control, minimal side effects, and good acceptability.

PMID- 22994021
TI  - Effect of cervical length to the efficacy of nifedipine and bed rest for
      inhibiting threatened preterm labor.
AB  - OBJECTIVE: To compare the success rates and gestational ages at delivery of
      nifedipine administration as a tocolytic agent to pregnant women with threatened
      preterm labor based on cervical length. MATERIAL AND METHOD: One hundred eighty
      eight pregnant women with threatened preterm labor between 26 and 35 weeks were
      enrolled in the present study. Cervical measurement was performed in all patients
      and divided in two groups. The first group, 60 cases, was patients with cervical
      length less than 30 mm. The second group, 128 cases, was patients with cervical
      length 30 mm or greater All women in each group were randomly inhibited uterine
      contraction with nifedipine and were bed rest. RESULTS: If the cervical length
      was 30 mm or greater; nifedipine and bed rest succeeded to inhibit uterine
      contraction without statistical significance. Nifedipine was appropriate for
      contraction inhibition when the cervical length was less than 30 mm with
      statistical significance. CONCLUSION: Nifedipine and bed rest can be used
      successfully to inhibit contractions in threatened preterm labor However
      nifedipine should be used if the cervical length is less than 30 mm. If cervical
      length is 30 mm or greater bed rest should be advised to avoid unnecessary
      medical intervention.

PMID- 22994022
TI  - Osteoporosis in different age-groups and various body mass index (BMI) ranges in
      women undergoing bone mass measurement at King Chulalongkorn Memorial Hospital.
AB  - OBJECTIVE: To determine percentage of osteoporosis at femoral neck and lumbar
      spine (L1-L4) in women with different age group and various BMI ranges. MATERIAL
      AND METHOD: The present study was conducted in 4528 women of > or =40 years who
      underwent first BMD measurement at King Chulalongkorn Memorial Hospital between
      2000 and 2010. Bone mineral density (BMD) of femoral neck (nondominant side) and
      lumbar spine (Li-L4) was measure by Dual-energy x-ray Absorptiometer (DXA). The
      percentage of osteoporosis was determined by WHO cutoff value using Thai
      nationwide reference database. RESULTS: The percentages of osteoporosis at
      femoral neck (FN) in age group of 40 to 49, 50 to 59, 60 to 69, and > or =70
      years were 6.2%, 7.4%, 24.4%, and 51.8% respectively The corresponding figures
      for lumbar spine (LS) were 3.4%, 5.6%, 12.7%, and 20.9% respectively. The
      percentage of osteoporosis seems to increase strikingly after 60 years at both
      sites. The percentage of osteoporosis at FN in underweight, normal weight,
      overweight and obesity were 52.1%, 20.3%, 15.7%, and 9.4% respectively. The
      corresponding figures for LS were 22.8%, 12%, 4.8%, and 5.9% respectively. Over
      30% of women of age > or =60 years with BMI of less than 23 kg/m2 had
      osteoporosis by the studied criteria. CONCLUSION: The percentage of osteoporosis
      seemed to be increasing with age and declining with BMI. Using the WHO cutoff
      value and Thai reference database, the percentage of femoral neck osteoporosis
      appeared to be higher than the lumbar spine. In the present study, the authors
      found that women of > or =60 years with BMI of less than 23 kg/m2 posed a
      substantial percentage of osteoporosis.

PMID- 22994023
TI  - Long-term efficacy of pre- and post-dilution online hemodiafiltration with
      dialyzer reuse.
AB  - OBJECTIVE: Growing evidence has demonstrated the potential survival benefit of
      online hemodiafiltration (HDF) over conventional hemodialysis (HD). Previous
      studies regarding online HDF utilized single-use dialyzer The present study was
      conducted to compare the long-term clinical parameters between pre- and post
      dilution online HDF with the reuse dialyzer MATERIAL AND METHOD: This 2-year
      historical cohort study was conducted in 20 chronic hemodialysis patients who had
      undergone thrice-a-week pre-dilution online HDF for at least one year. The
      patients were switched to post-dilution online HDF for another year. Reuse
      dialyzers were utilized in both methods. RESULTS: No pyrogenic reactions had been
      detected throughout the 2-year study period. The C-reactive protein (CRP) and
      nutritional parameters were in good normal ranges. The normalization of protein
      equivalent of nitrogen appearance (nPNA) was significantly higher during the post
      dilution period (1.25 +/- 0.22 vs. 1.11 +/- 0.14 g/kg/d, p < 0.01). Regarding
      adequacy of hemodialysis, the post-dilution online HDF showed significantly
      better Kt/V than the pre-dilution mode (2.46 +/- 0.35 vs. 2.35 +/- 0.35, p <
      0.05) whereas the predialysis beta2-microglobulin levels were not different
      (23.43 +/- 5.35 vs. 23.73 +/- 5.55 mg/L, NS). The numbers of reuse were
      comparable (17.3 +/- 2.6 vs. 16.4 +/- 2.7, NS). CONCLUSION: Utilizing reuse
      dialyzer in online HDF could provide efficacy, safety, cost saving, and
      environmental benefit. The post-dilution technique yielded the better adequacy
      and nutritional status without causing the limitation in the reuse number and
      would be the standard mode-of-choice for online HDEF

PMID- 22994024
TI  - Effectiveness of a preoperative single dose intravenous dexamethasone in reducing
      the prevalence of postoperative sore throat after endotracheal intubation.
AB  - OBJECTIVE: To evaluate the effectiveness of two-different doses of prophylactic
      dexamethasone intravenous administration in reducing the prevalence of
      postoperative sore throat following general endotracheal anesthesia. MATERIAL AND
      METHOD: All patients (105 cases) of different procedures of elective surgery
      scheduled to have general anesthesia performed with endotracheal intubations were
      included. The subjects randomized into three pre-operative intravenous
      substance/drug administrations, group I (35 cases) with normal saline 2 ml, group
      II (35 cases) with dexamethasone 4 mg, and group III (35 cases) with
      dexamethasone 8 mg, respectively. The prevalence of sore throat and its severity
      was assessed, using visual analogue scale (VAS), scores of O to 10; 0 = no pain,
      and 10 = most severe pain. RESULTS: Among three groups, the duration of surgery,
      and intubation-induced trauma had no statistical significance. The prevalence of
      sore throat at 1-hour/24-hour postoperative was 48.6/48.6%, 54.3/28.6%, and
      54.3/42.9% in group I, II, and III respectively, and without statistical
      significance. CONCLUSION: The intravenous dexamethasone had no significant
      effectiveness against postoperatively sore throat after endotracheal intubation.

PMID- 22994025
TI  - PSA density and prostate cancer detection.
AB  - OBJECTIVE: To evaluate the diagnostic value of prostate-specific antigen density
      (PSAD) and the appropriate cutoff for the detection of prostate cancer. MATERIAL
      AND METHOD: Between January 2008 and March 2011, 292 men with PSA levels between
      4 and 10 ng/mL underwent transrectal ultrasonography (TRUS) with prostate biopsy.
      The diagnostic value of PSA levels and PSAD were compared using receiver
      operating characteristic curves. RESULTS: Prostate cancer was diagnosed in 64
      (22%) of the 292 men who had PSA levels 4 to 10 ng/mL. The mean PSA level was
      6.96 ng/mL. The mean age was 66 years. The area under the curve (AUC) of PSA and
      PSAD were 0.475 and 0.665, respectively. The sensitivity and specificity of PSAD
      at cutoff of 0.15 was 78% and 43%, respectively CONCLUSION: PSAD was a better
      discriminator of prostate cancer than PSA for PSA levels less than 10 ng/ml. Our
      data suggested that a different PSAD cutoff than previously recommended need to
      be defined for Thai people.

PMID- 22994026
TI  - Causes of failure in total knee arthroplasty.
AB  - BACKGROUND: The number of primary total knee replacement procedures has rapidly
      increased worldwide because of the high success rates. The incidence of failure
      of total knee replacements has concurrently increased. Determining the causes of
      failure is very important for devising treatment and plan for future prevention
      strategies. MATERIAL AND METHOD: A retrospective study was done with patients who
      underwent revised total knee replacements in Siriraj Hospital between September
      2003 and March 2009. Patient demographic data, laboratory tests, radiographic
      studies, and intra-operative findings were used to categorize the causes of
      failure. RESULTS: One hundred eighty nine patients (31 male, 158 female) were
      included in the present study. The average age was 70.8 years. The average
      survival time after surgery was 6.42 years (ranging from 1 month to 22 years).
      The major causes of failure included aseptic loosening (52%), polyethylene wear
      (43%), and infection (31%). Infection (61%) was found in more than half the cases
      of early failure (< 3 years). Most cases of late failure (> 3 years) were due to
      aseptic loosening (74%), polyethylene wear (68%), and infection (14%). Male sex
      and early failure were strongly associated with failure secondary to infection,
      with odds ratios 4.5 and 8.8, respectively. CONCLUSION: There are different
      causes of early and late failure. The major cause of early failure was infection,
      while aseptic loosening and polyethylene wear played major roles in late failure.
      The number of failures due to infection was higher than observed from previous
      studies. Identification of the causes of failure of total knee replacement
      surgery from the same country or region will be useful for devising plans to
      manage and prevent failure in future surgeries.

PMID- 22994027
TI  - Factors predicting failure of conservative treatment in lumbar-disc herniation.
AB  - OBJECTIVE: To explore factors predicting failure of conservative treatment in
      lumbar-disc herniation. BACKGROUND: Sciatica due to lumbar-disc herniation is a
      common complaint of spine patients. Even though the natural course is favorable,
      surgery is necessary in at least 10% of cases. Current trends show surgery to be
      more cost-effective than prolonged conservative care. However; there is limited
      information about the usefulness of clinical and radiographic parameters to
      classify patients who are likely to fail conservative treatment. MATERIAL AND
      METHOD: Medical records of patients diagnosed with lumbar-disc herniation between
      January 1, 2007 and December 31, 2009 were studied. The records of patients in
      conservative and surgery groups were compared, for clinical features, MRI results
      and treatment modalities. RESULTS: Fifty cases (discectomy) and 50 controls
      (successful conservative treatment) were enrolled. Demographic data, presenting
      symptoms and physical examination did not differ apart from duration of symptoms.
      Logistic regression analysis did not find a significant association between
      percentage of canal compromised after controlling for disc-fragment size,
      duration of symptoms and types of disc herniation. However disc fragment size was
      strongly associated with surgical outcome (OR = 2.6). Duration of symptoms (OR =
      1.2) and sequestered type of lesion (OR = 12.3) were associated with surgery in
      this model. The use of physiotherapy and epidural steroid injections was lower
      but the failure rate was higher. CONCLUSION: Long-duration, sequestered
      herniation and large fragment are predictive of failure in the conservative
      treatment of lumbar-disc herniation.

PMID- 22994029
TI  - Anterior chamber contamination during phacoemulsification after povidone-iodine
      application.
AB  - OBJECTIVE: To determine the rate of anterior chamber contamination during
      phacoemulsification after applying 5% povidone-iodine prior to surgery. MATERIAL
      AND METHOD: One hundred eyes from 100 patients having phacoemulsification
      cataract surgery by a single surgeon at Ramathibodi Hospital between October 2010
      and March 2011 were included in the present study. Povidone-iodine 5% solution
      eye drops were used in all patients at least three minutes before the operation.
      Anterior chamber fluid was aspirated at the end of the procedure for culture in
      chocolate agar RESULTS: Anterior chamber fluid cultures were positive in three
      eyes (Pseudomanas oryzihabitans in 1 eye, Klebsiella pneumoni in 1 eye, and yeast
      in 1 eye). These three patients had no exaggerated or prolonged postoperative
      intraocular inflammation compared to others. No patients in the present study
      developed endophthalmitis. CONCLUSION: Povidone-iodine 5% solution eye drops
      before operation may control microbial contamination during phacoemulsification.

PMID- 22994028
TI  - Reliability and validity study of a Thai version of the Neck Disability Index in
      patients with neck pain.
AB  - OBJECTIVE: To evaluate the reliability and validity of the Thai version of the
      neck disability index (NDI) in neck pain patients. MATERIAL AND METHOD: The NDI
      was translated into Thai. The translation strategy used international standards.
      Forty-six Thai patients with neck pain were included in the present study. Thai
      version NDI, short form-36 (SF-36) and visual analogue scale (VAS) were completed
      by all subjects, twice, one week apart. The reliability and validity were
      subsequently analyzed. RESULTS: Intraclass correlation coefficient score for test
      retest reliability was 0.986. Cronbach's alpha for internal consistency was
      calculated as 0.925. For concurrent validity, the relation between NDI and VAS
      was investigated, the r value was 0.886 (p < 0.001). For construct validity, the
      relation between NDI and the Thai version of SF-36 was -0.427. The mental health
      component was highest correlated with NDI. CONCLUSION: The Thai version of NDI is
      a valid and reliable measurement method for evaluating neck pain disability.

PMID- 22994030
TI  - Risk factors for contact lens related microbial keratitis: a case-control study.
AB  - OBJECTIVE: To evaluate the risk factors that may contribute to microbial
      keratitis in contact lens wearers. MATERIAL AND METHOD: This prospective case
      control study included 52 patients with contact lens related keratitis treated
      between 1 December 2006 and 15 October 2007 at the Faculty of Medicine, Siriraj
      Hospital. Controls were sixty-three contact lens users attending with disorders
      unrelated to contact lens wear All subjects with informed consent were
      interviewed about demographic data, types of contact lens and contact lens
      solutions, contact lens use past the recommended replacement date, overnight
      wear, and lens hygiene. Odds ratio (OR, estimates of relative risks) and 95%
      confidence interval (CI) were calculated through multivariable logistic
      regression analysis. RESULTS: The use of contact lens past the replacement date
      caused the highest risk of developing microbial keratitis (OR = 9.1; CI 1.8-45.4,
      p = 0.005). Overnight wear of lenses (OR = 2.9, CI 1.3-6.2, p = 0.012) and poor
      lens hygiene (OR = 2.3, CI 1.0-5.1, p = 0.007) significantly increased the risk
      of microbial keratitis, respectively. None of the other risk factors showed a
      significant association. CONCLUSION: The significant risk factors for contact
      lens related microbial keratitis in the present study were the use of contact
      lens past the replacement date, overnight wear, and poor lens hygiene. Thus, the
      appropriate advice of contact lens care and usage may reduce the risk of
      microbial keratitis in contact lens wearers.

PMID- 22994031
TI  - The central corneal light reflex ratio from photographs derived from a digital
      camera in young adults.
AB  - OBJECTIVE: To determine the normal range of Central Corneal Light Reflex Ratio
      (CCLRR) from photographs of young adults. MATERIAL AND METHOD: A digital camera
      equipped with a telephoto lens with a flash attachment placed directly above the
      lens was used to obtain corneal light reflex photographs of 104 subjects, first
      with the subject fixating on the lens of the camera at a distance of 43
      centimeters, and then while looking past the camera to a wall at a distance of
      5.4 meters. Digital images were displayed using Adobe Photoshop at a
      magnification of l200%. The CCLRR was the ratio of the sum of distances between
      the inner margin of cornea and the central corneal light reflex of each eye to
      the sum of horizontal corneal diameter of each eye. Measurements were made by
      three technicians on all subjects, and repeated on a 16% (n=17) subsample.
      RESULTS: Mean ratios (standard deviation-SD) from near/distance measurements were
      0.468 (0.012)/0.452 (0.019). Limits of the normal range, with 95% certainty, were
      0.448 and 0.488 for near measurements and 0.419 and 0.484 for distance
      measurements. Lower and upper indeterminate zones were 0.440-0.447 and 0.489
      0.497 for near measurements and 0.406-0.418 and 0.485-0.497 for distance
      measurements. More extreme values can be considered as abnormal. The
      reproducibility and repeatability of the test was good. CONCLUSION: This method
      is easy to perform and has potential for use in strabismus screening by
      paramedical personnel.

PMID- 22994032
TI  - Diagnostic accuracy of multidetector computed tomography (MDCT) in evaluation for
      mediastinal invasion of esophageal cancer.
AB  - OBJECTIVE: Determine diagnostic accuracy of evaluation for mediastinal invasion
      of esophageal cancer by multidetector computed tomography (MDCT) as compared with
      post-operative histopathology staging. MATERIAL AND METHOD: The present study
      retrospectively analyzed the 64-slice MDCT of twenty-one patient's diagnosis with
      esophageal cancer who received surgical treatment in Siriraj Hospital. Patients
      were enrolled between June 1, 2004 and Dec 31, 2009. Twenty-one CT images of
      chest were evaluated by two radiologists without knowing each patient's history
      as determined by surgical and pathology findings. Image analysis was determined
      for evaluating tumor location, wall appearance, findings of direct mediastinal
      extension. Accuracy, sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV) were evaluated for tumor staging and nodal
      staging. RESULTS: Concordance between the two different readers for the
      interpretations with a kappa coefficient to assess interobserver variation of0.2
      to 0.9 suggests only slight agreement between the two readers. The overall
      sensitivity, specificity, PPV NPV and accuracy of CT T3 staging were 75%, 78%,
      66.7%, 84.6%, and 77.3% respectively. The CT T4 staging had sensitivity 75%,
      specificity 85.7%, PPV 75%, NPV85.7%, and accuracy 81.8%. In N staging, NO
      staging from CT study had sensitivity 50%, specificity 33%, and accuracy 38%. NI
      staging from CT study had sensitivity 33%, specificity 50%, and accuracy 38%.
      CONCLUSION: 64-slice MDCT can be evaluated for mediastinal tumor invasion of
      esophageal cancer with high sensitivity, specificity, and accuracy. The
      metastatic node and reactive lymphadenopathy in esophageal cancer were equivocal
      to discriminating from CT findings, especially using 1 cm in diameter of short
      axis as cut point.

PMID- 22994033
TI  - Comparison of bacterial count in tap water between first burst and running tap
      water.
AB  - OBJECTIVE: To compare the number of bacterial counts in tap water at first burst
      and running tap water. MATERIAL AND METHOD: The present study was performed in
      thirty-two first burst water samples and twenty-nine running tap water samples
      after two minutes, collected from an operation room at one standard hospital and
      analyzed for the mean, median, and 95% achieved confidence interval of CFU/ml.
      All water samples were cultured and investigated for total bacterial counts,
      which were expressed as colony forming unit per milliliter (CFU/ml). RESULTS: The
      bacterial count was statistically significantly about three times higher in the
      samples of the first burst tap water in comparison with the group of samples
      after letting the tap water run for two minutes 98.7, 78.5, 60.5-120.0 vs. 29.1,
      25.8, 16.6-33.2 CFU/ml. CONCLUSION: Two minutes running tap water contains about
      three times less bacterial count than first burst tap water

PMID- 22994034
TI  - Quality of life among the navies and their spouses survivors, six months after
      the tsunami disaster in Phang-Nga Naval Base, Thailand.
AB  - OBJECTIVE: Identify the consequences for the survivors of the tsunami disaster on
      health related quality of life among members of the Navy and their spouses, six
      months after the disaster. MATERIAL AND METHOD: Using a structured questionnaire
      modified from the MOS SF-36. Four hundred thirty four subjects participated in
      the present study. The sample was male (77%), married (67%) and mean age was 34
      years old. RESULTS: The quality of life scores among member of the Navy or their
      spouses were lower than the 2006 Thailand normative data in almost all subscales
      except physical functioning, bodily pain, and social functioning subscales. The
      major consequence of the Tsunami was mental health problems. A majority of the
      survivors who seriously experienced mental problems were female, low education,
      decreased income, loss of one's family members/loved ones, or property.
      CONCLUSION: To improve their quality of life, these people required appropriate
      social support and physical and mental health care. Bodily pain was the only an
      indicator subscale of QOL that was statistically significantly associated with
      tsunami exposure. The QOL measures provided essential data and information that
      helped healthcare providers identify survivors' needs and outcomes and therefore,
      knowledge of the changes in QOL over the time after tsunami might help guide
      health programs to efficiently allocate resources at different times.

PMID- 22994036
TI  - An uncommon cause of compressive myelopathy misdiagnosed as transverse myelitis.
AB  - Though spontaneous spinal epidural hematoma is a very uncommon cause of spinal
      cord compression, early correct diagnosis is crucial for final clinical outcome.
      A case of spontaneous spinal epidural hematoma with similar clinical presentation
      to transverse myelitis was reported. Careful clinical correlation and multiple
      sequences of spinal magnetic resonance images are critical factors for early
      diagnosis.

PMID- 22994035
TI  - Spontaneous perforation of pyometra in an elderly woman: a case report.
AB  - Pyometra is an uncommon gynecologic condition that usually develops in elderly
      women. Most of the cases result from cervical occlusion by malignant or benign
      tumors, surgery, radiotherapy, or atrophic cervicitis. A spontaneous perforation
      of the uterus with generalized peritonitis is an extremely rare complication of
      pyometra and carries significant morbidity and mortality. Establishing a correct
      diagnosis preoperatively is not easy due to the non-specificity of the symptoms.
      The authors present a case report of peritonitis caused by spontaneously
      perforated pyometra that was diagnosed intraoperatively. The cervical canal was
      not occluded and the cause of perforation remains obscure.

PMID- 22994037
TI  - The bilateral supraorbital minicraniotomies for total removal of giant
      suprasellar-subchiasmatic tumors.
AB  - Minimally invasive supraorbital approach through minicraniotomy have been
      proposed and developed for the treatment of anterior cranial fossa pathology and
      lesions around sellae. The author has used this concept of smaller operative
      corridors to treat the suprasellar tumors. In cases of large suprasellar tumors,
      mainly of subchiasmatic location, that radical removal could not be achieved with
      unilateral approach, an additional contralateral supraorbital approach was
      proceeded to accomplish radical removal. Through bicoronal incision, approach via
      bilateral supraorbital minicraniotomies was used to treat three cases of giant
      suprasellar-subchiasmatic tumors, with the greatest dimension of more than 4 cm,
      between 2005 and 2010. The result of treatment is satisfactory. There was no
      operative mortality or new major neurological deficit. All tumors were totally
      removed with marked improvement of visual deficit in two patients. No adjuvant
      radiotherapy was given. All were recurrence free 18 months, 4 years, and 5 years
      after the surgery. The major advantage of this approach is the excellent
      visualization and identification of the plane between the tumor and contralateral
      optic nerve through each corridor This will facilitate complete decompression of
      both optic nerves and enhance radical removal of the tumor while avoiding risk of
      injury to the nearby neurovascular structures. However, the approach-related
      disadvantage is the risk of olfactory dysfunction from bilateral olfactory nerve
      damage, which can be further improved by a refinement of the techniques.

PMID- 22994038
TI  - Rhino-orbital fungal infection: two cases report.
AB  - Rhino-orbital fungal infections are serious and life threatening complications of
      immunocompromised host. The authors reported two cases of rapid progressive
      proptosis and eyelid necrosis of immunocompromised patients who suffered from
      highly malignant T-celled lymphoblastic leukemia/lymphoma and congenital heart
      disease with multiple anomalies. Although early diagnosis was made and prompt
      treatments including medical and surgical interventions were performed, both
      patients died.

PMID- 22994039
TI  - The right ovarian artery arising from the right inferior phrenic artery: a case
      report.
AB  - OBJECTIVE: To report a case of the right ovarian artery arising from the right
      inferior phrenic artery. MATERIAL AND METHOD: The authors carried out the
      standard dissection survey of 810 embalmed female cadavers between 1983 and 2010.
      RESULTS: The authors encountered a case of the right ovarian artery arising from
      the right inferior phrenic artery in a donated cadaver aged 53 years at decease.
      CONCLUSION: With the advent of intra-abdominal laparoscopic techniques, the
      anatomy of the ovarian artery has assumed much more importance.

PMID- 22994040
TI  - [Epidemiological characteristics of chronic prostatitis in China].
AB  - Chronic prostatitis (CP) is a common urinary disease that has been challenging
      urologists and seriously affects the patient's mental and physical health. For
      the reasons of its ambiguous etiology, complex and varied clinical symptoms,
      controversial diagnostic methods and long-term treatment, the therapeutic effect
      on CP is often unsatisfactory to both patients and urologists. This review
      focuses on the prevalence and age distribution of CP, incidence of different
      types of prostatitis, and the association of CP with climate, occupation, related
      diseases, lifestyle and education level, with a special emphasis on the current
      epidemiological characteristics of CP in China.

PMID- 22994041
TI  - [Nuclear matrix proteins differentially expressed in human prostate cancer cell
      lines and benign prostatic hyperplasia epithelial cell line].
AB  - OBJECTIVE: To compare the expression of nuclear matrix proteins (NMPs) in benign
      prostatic hyperplasia (BPH) epithelial cell line BPH-1 versus those in androgen
      dependent human prostate cancer cell line LNCap and androgen-independent prostate
      cancer cell line PC-3. METHODS: We isolated NMPs from the BPH-1, LNCap and PC-3
      cell lines by 2-dimensional electrophoresis (2-DE), analyzed the differentially
      expressed proteins by matrix-assisted laser desorption / ionization time of
      flight mass spectrometry (MALDI-TOF-MS), and identified them by peptide mass
      fingerprint and database searching. RESULTS: We successfully obtained well
      resolved reproducible 2-DE patterns of NMPs in human prostate cancer cell lines,
      identified 12 differentially expressed NMPs including enzymes, regulatory
      proteins, RNA-binding protein and various other factors, 3 up-regulated and 9
      down-regulated in prostate cancer cell lines. CONCLUSION: There are obvious
      differences in the expressions of NMPs between human prostate cancer cell lines
      and benign prostatic hyperplasia epithelial cell line.

PMID- 22994042
TI  - [Inhibitory effect of dihydroartemisinin on the growth of human prostate cancer
      PC-3M cells and its mechanism].
AB  - OBJECTIVE: To study the effects of dihydroartemisinin on the apoptosis of and the
      vascular endothelial growth factor (VEGF) expression in prostate cancer cell line
      PC-3M in androgen-independent prostate cancer. METHODS: PC-3M cells were treated
      with different doses (0, 25, 50 and 100 micromol/L) of dihydroartemisinin for 48
      hours, their growth activity analyzed by MTT colorimetric assay and flow
      cytometry, and changes in the activities of caspase-3 and -8 detected by
      colorimetric assay. The expression of VEGF mRNA was determined by semi
      quantitative RT-PCR, and that of the VEGF protein by Western blotting. RESULTS:
      Compared with the 0 micromol/L control group, the 25, 50 and 100 micromol/L
      dihydroartemisinin groups showed significantly increased apoptosis of PC-3M cells
      ([2.92 +/- 0.45]% vs [8.85 +/- 0.74]%, [12.83 +/- 0.84]% and [18.65 +/- 1.24]%, P
      < 0.01), and dose-dependent increase in the activities of caspase-8 ([0.47 +/-
      0.05 ] U/microg vs [1.22 +/- 0.15], [1.76 +/- 0.07] and [2.91 +/- 0.24] U/microg,
      P < 0.01) and caspase-3 ([0.44 +/- 0.07] U/microg vs [0.95 +/- 0.08], [1.48 +/-
      0.14] and [2.92 +/- 0.45] U/microg, P < 0.01). The expressions of VEGF mRNA and
      protein were decreased in a concentration-dependent manner. CONCLUSION:
      Dihydroartemisinin can significantly suppress the growth of PC-3M cells, promote
      their apoptosis and reduce the expressions of VEGF mRNA and protein, which may
      serve to explain its inhibitory effect on tumor and angiogenesis.

PMID- 22994043
TI  - [RNA interference of RelB enhances the radiosensitivity of prostate cancer cell
      line RM-1 in mice].
AB  - OBJECTIVE: To investigate the effect of RNA interference of the RelB gene on the
      radiosensitivity of the mouse prostate cancer cell line RM-1 and its mechanism.
      METHODS: We constructed RelB siRNA-expressing lentiviral vectors targeting the
      RelB gene with the molecular biological technique, and determined the expressions
      of RelB mRNA and protein on radiation after transfection with siRelB mediated by
      liposome using RT-PCR and Western blot, respectively. We also detected the
      apoptosis of RM-1 cells by FCM assay and their radiosensitivity by clonogenic
      assay. RESULTS: The expressions of RelB mRNA and protein were significantly lower
      in the RM-1 cells than in the control and negative interference groups after
      transfection with RelB siRNA (P < 0.05), while the apoptosis of RM-1 cells
      remarkably higher in the siRelB-RM-1 than in the control group after radiation
      treatment (P < 0.05). The activity of MnSOD was markedly decreased (P < 0.05),
      and the radiosensitization rate of the RM-1 cells in the RelB-RM-1 group was 5.13
      after radiation treatment. CONCLUSION: RNA interference of the RelB gene could
      enhance the radiosensitivity of the mouse prostate cancer cell line RM-1, which
      might be associated with its inhibition of Mn-SOD expression and induction of
      cell apoptosis.

PMID- 22994044
TI  - [Inhibitory effect of losartan on prostatic hyperplasia in spontaneous
      hypertension rats and its pathophysiological mechanism].
AB  - OBJECTIVE: To investigate the effect of losartan on prostatic hyperplasia in
      spontaneous hypertension rats (SHRs) and its pathophysiological mechanism.
      METHODS: We randomly divided 36 male SHRs into three groups of equal number to be
      treated intragastrically with high-dose losartan (30 mg per kg per d), low-dose
      losartan (15 mg per kg per d) and distilled water (control group). After 6 weeks
      of intervention, we measured the body weight and tail artery blood pressure of
      the rats and compared them with the baseline data. We collected blood from the
      heart for determination of the levels of serum angiotensin II (Ang II), insulin
      like growth factor-1 (IGF-1) and interleukin-6 (IL-6) by enzyme-linked
      immunosorbent assay (ELISA), and harvested their prostates for measurement of
      their weight, observation of the tissue ultrastructures under the electron
      microscope and detection of the expression of endothelial nitric oxide synthase
      (eNOS) in the prostate tissue by immunohistochemistry. RESULTS: Compared with the
      control group, the low- and high-dose losartan groups showed significant
      decreases in systolic blood pressure ([203.75 +/- 10.28] vs [184.54 +/- 16.90]
      mmHg, P = 0.013; [203.75 +/- 10.28] vs [166.88 +/- 14.74] mmHg, P = 0.001) and
      diastolic blood pressure ([151.58 +/- 9.96] vs [136.71 +/- 14.28] mmHg, P =
      0.022; [151.58 +/- 9.96] vs [122.71 +/- 11.56] mmHg, P < 0.001) of the lower tail
      artery after treatment, as well as in the prostate weight ([0.73 +/- 0.08] vs
      [0.64 +/- 0.10] mg, P = 0.011; [0.73 +/- 0.08 ] vs [0.50 +/- 0.17] mg, P <
      0.001). Electron microscopy revealed edema of the basal and columnar epithelial
      cells, concentrated and marginated heterochromatin and widened nuclear gap of
      interstitial fibroblast nuclei, and reduced mitochondria and endoplasmic reticula
      in the low-dose losartan group, and even more obvious in the high-dose group. The
      level of serum Ang II was remarkably higher in the low- and high-dose losartan
      groups than in the control ([61.32 +/- 2.49] vs [54.85 +/- 7.20] pg/ml, P =
      0.021; [65.49 +/- 6.78] vs [54.85 +/- 7.20] pg/ml, P < 0.001]) , that of serum
      IGF-1 was lower in high-dose losartan than in the control group ([1.50 +/- 0.11]
      vs [1.60 +/- 0.10] ng/ml, P = 0.03), but the serum IL-6 levels exhibited no
      significant differences among the three groups. The expression of eNOS in the
      prostate tissue was significantly higher in the losartan groups than in the
      controls (P = 0.022), even higher in the high-dose than in the low-dose group.
      CONCLUSION: Losartan can suppress the progression of prostate hyperplasia in
      spontaneous hypertension rats by inhibiting RAS, IGF-1 and angiogenesis.

PMID- 22994045
TI  - [Three-step sperm retrieval for 73 non-obstructive azoospermia patients].
AB  - OBJECTIVE: To investigate the value and clinical application of the Three-Step
      Sperm Retrieval method in improving the sperm retrieval rate for non-obstructive
      azoospermia (NOA) patients. METHODS: Seventy-three NOA patients underwent Three
      Step Sperm Retrieval in the following order of procedures: testicular fine needle
      aspiration (TFNA), testicular sperm extraction (TSE), and microdissection
      testicular sperm extraction (MD-TSE). The testicular tissue obtained from each
      step was observed for spermatozoa under the 400-fold inverted microscope. If
      spermatozoa were found in one step, the operation would be stopped; otherwise,
      the next step would be carried out. The testicular tissue was subjected to
      pathological examination. RESULTS: Spermatozoa was found in the testicular tissue
      in 38.4% of the cases (28/73) at TFNA as the first step, in 52.1% (38/73) at TFNA
      and TSE, and in 64.4% (47/73) at TFNA, TSE and MD-TSE. Pathological examination
      showed 25 of the cases to be Sertoli cell-only syndrome, 21 to be sperm
      maturation arrest and the other 27 to be hypospermatogenesis, in which
      spermatozoa were found in 10, 14 and 23 cases, respectively. CONCLUSION: The
      Three-Step Sperm Retrieval method can significantly improve the sperm retrieval
      rate for NOA patients. And the sperm retrieval rate is associated with the
      pathological type of the testicular tissue, a higher rate with
      hypospermatogenesis.

PMID- 22994046
TI  - [Diagnosis and treatment of epididymal obstructive azoospermia by microsurgery].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of epididymal obstructive
      azoospermia (OA) by microsurgery. METHODS: We performed surgical scrotal
      exploration for 57 cases of OA whose obstruction was suspected to be in the
      epididymis. Those confirmed to be epididymal OA cases and with motile sperm in
      the epididymis underwent longitudinal-2-suture intussusceptive vasoepididymostomy
      (LIVES). And for those with sperm in the epididymal head only or with bilateral
      obstruction or absence of the vas deferens in the distal epididymis, the sperm
      were collected and subjected to cryopreservation for intracytoplasmic sperm
      injection (ICSI). After surgery, the patients were followed up for observation of
      the semen parameters and the rate of pregnancy. RESULTS: Of the total number of
      patients, 53 (92.9%) were diagnosed with epididymal OA by scrotal exploration, 47
      (82.5%) underwent microsurgery, and the other 10 (17.5%) received sperm
      cryopreservation. At 1 to 18 months after surgery, motile sperm were found in the
      ejaculate in 46.8% of the cases (22/47), natural pregnancy in 10.6% (5/47), and
      ICSI pregnancy in 18.5% (6/32). CONCLUSION: With the development of microsurgery,
      non-invasive means should be the first choice for the diagnosis of OA. And
      surgical exploration can be employed to determine the location of obstruction and
      the option for treatment.

PMID- 22994047
TI  - [Primary male urethral cancer: management and prognosis].
AB  - OBJECTIVE: To further investigate the management and prognosis of primary
      urethral cancer in male. METHODS: We treated 3 cases of primary urethral cancer
      from 2001 to 2011 and followed them up for recurrence and survival. RESULTS: The
      3 male patients all received adjuvant radiotherapy and/or chemotherapy, and 2 of
      them were treated by distal urethrectomy, while the other underwent no surgery.
      Follow-up visits revealed 2 cases of metastasis and 1 case of death. CONCLUSION:
      Primary cancer of the male urethra is a rare malignancy with poor prognosis, for
      which radical resection is the main treatment method. Those in the relatively
      advanced stage can be treated by a combined method of surgery, radiotherapy and
      chemotherapy.

PMID- 22994048
TI  - [Glans-preserving surgery for superficial penile cancer].
AB  - OBJECTIVE: To investigate the safety and feasibility of glans-preserving surgery
      in the treatment of superficial penile cancer (SPCa). METHODS: We retrospectively
      analyzed the clinical data of 21 cases of SPCa treated by glans-preserving
      surgery in our hospital from January of 2003 to March of 2010. RESULTS: The study
      included 21 SPCa patients aged 36 to 57 (mean 46) years, with superficial lesions
      involving the glans penis, coronary sulcus or shaft skin. The tumors were staged
      and graded TaG1 in 6 cases, TaG2 in 5, TisG1 in 2, TisG2 in 4, T1G1 in 3, and
      T1G2 in 1. All the patients underwent glans-preserving surgery to preserve the
      normal appearance and functional integrity of the glans penis, and all returned
      to normal sexual activity 1 month after operation, with good sexual function and
      sexual satisfaction. Postoperative follow-up lasted 2 to 7 (mean 5) years, and 2
      cases of recurrence in situ found at 6 and 9 months, respectively, which were
      successfully managed by a second glans-preserving surgery. CONCLUSION: Glans
      preserving surgery is an effective method for superficial penile cancer. With
      proper selection of the patients, this procedure is technically safe, maximally
      preserves the penile appearance, and least affects the patients' sexual
      satisfaction.

PMID- 22994050
TI  - [Measurement of MIP-1alpha and TNF-alpha in seminal plasma and its clinical
      significance].
AB  - OBJECTIVE: To observe changes in the concentrations of MIP-1alpha and TNF-alpha
      and their influence on sperm in the seminal plasma of infertile males. METHODS:
      We measured the concentrations of MIP-1alpha and TNF-alpha in the seminal plasma
      of 110 infertile patients and 30 normal fertile men by ELISA and
      radioimmunoassay, and compared them with sperm concentration, sperm viability,
      sperm motility, leukocytospermia and serum anti-sperm antibodies (AsAb). RESULTS:
      The infertility group, particularly the oligospermia cases, showed significantly
      higher concentrations of MIP-1alpha and TNF-alpha in the seminal plasma ([179.45
      +/- 24.54] pg/ml and [4.66 +/- 2.01] ng/ml) than the normal fertile men ([89.64
      +/- 13.27] pg/ml and [2.90 +/- 1.23] ng/ml) (P < 0.01). In comparison, the
      concentrations of MIP-1alpha and TNF-alpha were (196.04 +/- 23.54) pg/ml and
      (5.31 +/- 2.47) ng/ml versus (154.22 +/- 26.38) pg/ml and (3.94 +/- 2.09) ng/ml
      in the poor and normal sperm viability groups (P < 0.05 or P < 0.01), (210.39 +/-
      21.43) pg/ml and (5.14 +/- 2.61) ng/ml versus (139.87 +/- 27.62) pg/ml and (4.11
      +/- 2.26) ng/ml in the low and normal sperm motility groups (P < 0.05 or P <
      0.01), (203.14 +/- 24.65) pg/ml and (5.28 +/- 2.66) ng/ml versus (155.76 +/-
      21.42) pg/ml and (4.04 +/- 2.24) ng/ml in the leukocytospermia and non
      leukocytospermia groups (P < 0.05 or P < 0.01), and (234.05 +/- 27.60) pg/ml and
      (5.63 +/- 2.31) ng/ml versus (124.85 +/- 23.56) pg/ml and (3.69 +/- 2.15) ng/ml
      in the serum AsAb positive and negative groups (P < 0.05 or P < 0.01), most
      significantly increased in the serum AsAb positive group. CONCLUSION: The
      concentrations of MIP-1alpha and TNF-alpha in the seminal plasma are closely
      related with sperm count and function, and their detection helps to assess the
      severity of male infertility and improve its clinical treatment.

PMID- 22994049
TI  - [Effects of oral contraceptive pretreatment on controlled ovarian
      hyperstimulation and outcomes of IVF-ET].
AB  - OBJECTIVE: To investigate the effects of oral contraceptive pretreatment (OCP) in
      patients with polycystic ovarian syndrome (PCOS) undergoing controlled ovarian
      hyperstimulation for IVF-ET. METHODS: We randomly divided 85 patients with P-COS
      undergoing IVF-ET into an OCP (n = 53) and a control group (n = 32), the former
      received OCP, while the latter did not before the cycle. We retrospectively
      analyzed the data of the patients for the ovulation promoting effect of OCP and
      its influence on the incidence of ovarian hyperstimulation syndrome (OHSS) and
      outcomes of IVF-ET. RESULTS: Compared with the control group, OCP significantly
      reduced the formation of ovarian cyst (P < 0.05), remarkably increased the
      duration of gonadotropin stimulation and consumption (P < 0.01) , and markedly
      raised the percentage of mature ova (87.92% vs 92.85%, P < 0.05). But no
      significant differences were observed between the two groups in the incidences of
      moderate and severe OHSS, number of retrieved oocytes, and rates of
      fertilization, miscarriage and clinical pregnancy. CONCLUSION: OCP for patients
      with PCOS can help to control the time of ovarian stimulation, improve the
      synchronism of follicular development, and increase the duration of gonadotropin
      stimulation and consumption, but cannot change the incidences of moderate and
      severe OHSS.

PMID- 22994051
TI  - [Prostatic neuroendocrine cells and their association with chronic prostatitis].
AB  - Neuroendocrine cells are abundant in all the body tissues and organs as well as
      the nervous system, either the central or the peripheral nervous system. In the
      normal prostate tissue, there are a few neuroendocrine cells, too, in addition to
      basal and epithelial cells. Prostatic neuroendocrine cells play the function of
      regulating the development, secretion and differentiation of the prostate. Recent
      studies show that prostatic neuroendocrine cells may be involved in the
      pathogenesis of chronic prostatitis through their activity and secreted products.
      This article presents an overview on the origin, distribution, morphology,
      structure, secretion and functions of prostatic neuroendocrine cells and their
      association with chronic prostatitis.

PMID- 22994052
TI  - [Caveolin-1: a novel biomarker for prostate cancer].
AB  - For lack of the biomarker, early diagnosis of prostate cancer is often difficult.
      Caveolin-1 (Cav-1) is an important oncogene and a major structural coat protein
      of caveolae, which is involved in multiple cellular functions including molecular
      transport, cell adhesion, and signal transduction, as well as in the development
      and progression of prostate cancer. Cav-1 is secreted as a biologically active
      molecule that promotes cell survival and angiogenesis within the tumor
      microenvironment, and is overexpressed in the metastatic and primary sites of
      human prostate cancer. Secreted Cav-1 can be detected in the peripheral blood,
      and its expression level has an indicative value in the diagnosis and prognosis
      of prostate cancer. This review focuses on the structure and biological
      characteristics of Cav-1 and its correlation with prostate cancer.

PMID- 22994053
TI  - [In vivo study of antifertility and anti-inflammatory effects of compound Kucen
      gel].
AB  - OBJECTIVE: To study the antifertility and anti-inflammatory effects of compound
      Kucen gel in vivo. METHODS: As antifertility experiment, we randomly divided 60
      female SD rats into six groups of equal number: normal saline, blank gel, low-,
      medium- and high-dose compound Kucen gel (0.05, 0.10 and 0.15 g/g), and positive
      control (4% nonoxynol gel) to receive intravaginal administration of 200 microl
      of respective agent, followed by copulation with male rats in a 1:1 ratio. At 12
      days after successful mating, the female rats were dissected for calculation of
      the embryos and the rate of contraception. As an anti-inflammatory trial, we
      established a mouse model of inflammation by applying xylene to the pinna, and
      equally randomized 60 Kunming mice to six groups as in the former experiment. We
      determined the degrees and average rates of swelling inhibition in the left ear.
      RESULTS: High-dose compound Kucen gel achieved a fertility-inhibition rate of
      100% in the female rats, the number of embryos significantly lower than in the
      normal saline group (0.00 +/- 0.00 vs 11.00 +/- 2. 00, P < 0.05), but with no
      statistically insignificant difference from that of the positive control (0.00 +/
      0.00, P > 0.05). High-dose compound Kucen gel also markedly suppressed swelling
      in the left ear of the mice, with an inhibition rate of 52.3%, the average
      swelling degree significantly lower than in the normal saline group (10.17 +/-
      2.56 vs 21.32 +/- 3.17, P < 0.01), but not remarkably different from that of the
      positive control (8.53 +/- 1.89, P > 0.05). CONCLUSION: Compound Kucen gel, with
      its strong antifertility and anti-inflammatory effects, deserves further study
      and clinical application.

PMID- 22994055
TI  - [Efficacy of compound xuanju capsule on type-III prostatitis-related sexual
      dysfunction].
AB  - OBJECTIVE: To investigate the value of Compound Xuanju Capsule in the treatment
      of type-III prostatitis-related sexual dysfunction. METHODS: We randomly divided
      90 type-III prostatitis patients with sexual dysfunction diagnosed by NIH
      clinical criteria into an experiment group and a control group to be treated with
      Compound Xuanju Capsule and antibiotics, respectively. We analyzed the
      therapeutic results based on the scores on chronic prostatitis symptom index
      (CPSI), prostatitis-related sexual function index (PSFI ) and self-rating anxiety
      scale (SAS), and compared them between the two groups and with the baseline data.
      RESULTS: The degree of prostatitis-related sexual dysfunction was not correlated
      with that of prostatitis symptoms. Prostatitis symptoms and sexual function were
      significantly improved in the experiment group than in the control (P < 0.05),
      and the SAS score was markedly lower in the former than in the latter (P < 0.05).
      CONCLUSION: Compound Xuanju Capsule can not only alleviate the symptoms of type
      III prostatitis, but also improve its related sexual dysfunction and anxiety.

PMID- 22994054
TI  - [Combination of compound Xuanju capsule and tamoxifen citrate for idiopathic
      oligozoospermia].
AB  - OBJECTIVE: To evaluate the clinical effects of Compound Xuanju Capsule combined
      with tamoxifen citrate on the seminal parameters of men with idiopathic
      oligozoospermia. METHODS: We equally assigned 120 men with idiopathic
      oligozoospermia to receive Compound Xuanju Capsule plus tamoxifen citrate
      (experiment group) or tamoxifen citrate alone (control group). After 3 months of
      medication, we compared the concentration and total number of sperm with the
      baseline, and analyzed the influence of the duration of natural infertility on
      the therapeutic effect. RESULTS: Both the concentration and total number of sperm
      were significantly increased in both the experiment and the control groups after
      3 months of medication as compared with the baseline (P < 0.05), and the
      increases were even more significant in the former than in the latter group (P <
      0.05). The therapeutic efficacy was remarkably better in the patients with
      natural infertility < or = years than in those > 3 years (P < 0.05). CONCLUSION:
      Compound Xuanju Capsule combined with tamoxifen citrate produces satisfactory
      results in the treatment of idiopathic oligozoospermia, and therefore can be used
      as a first-line therapy for this disease.

PMID- 22994057
TI  - [The correction of dysipidemia in patients presenting with coronary heart disease
      in the course of the spa and resort-based treatment].
AB  - A total of 60 patients presenting with coronary heart disease (CHD) were treated
      at the Kislovodsk military health resort. The objective of the work was to
      develop a non-medicamental therapeutic modality for their rehabilitative
      treatment and correction of disordered lipid metabolism. The balneotherapeutic
      treatment influencing one of the etiopathogenetic mechanisms underlying CHD
      resulted in the well-apparent tendency toward a decrease of the degree of
      dyslipidemia (reduction in the total cholesterol level, cholesterol of low
      density lipoproteins, and atherogenicity index in the absence of clinically
      significant adverse events.

PMID- 22994056
TI  - [The correction of cognitive and psychological disorders in the patients
      presenting with vertebrogenic pain syndrome].
AB  - The objective of the present study was the dynamic estimation of the intensity of
      pain syndrome with the use of a visual-analog scale (VAS), characteristics of the
      psychological status and cognitive disorders, quality of life, and brain
      electrogenesis in 50 patients presenting with vertebrogenic pain syndrome of
      lumbar-sacral localization. It was shown that long-standing pain syndrome plays
      the dysadaptive role, causes structural and functional changes in the central
      nervous system (CNS), and is responsible for psychoemotional and cognitive
      disorders. The introduction of transcranial stimulation in the combined treatment
      of such patients promotes correction and reversibility of the above disorders,
      enhances the efficacy of electrotherapy, and improves the quality of life in the
      subjects with vertebrogenic pain syndrome.

PMID- 22994058
TI  - [The combined application of hypoxytherapy and oxygen therapy for the spa and
      resort-based treatment of bronchial asthma].
AB  - We undertook the comprehensive examination and treatment with the interval
      hypoxic training and enteral oxygen therapy of 285 patients presenting with mild
      and moderately severe bronchial asthma. The study has demonstrated the
      improvement of oxygen supply to various organs at all stages of its mass transfer
      and the enhanced oxygen consumption by the tissue. These effects promoted
      normalization of the function of the respiratory system, characteristics of the
      exhaled air condensate, the state of the pro-oxidant and anti-oxidant systems.
      The data obtained confirm the high efficacy of application of the combined
      therapeutic modality including interval hypoxic training and enteral oxygen
      therapy for the treatment of patients with bronchial asthma. Its clinical effect
      was achieved in the first place due to the activation of the mechanisms of
      adaptation to interval hypoxia, such as the improvement of the alveolar
      ventilation process during breathing, and blood circulation patterns. The
      beneficial influence on the mechanisms of adaptation to hypoxia and oxygen leads
      to the significant improvement of blood respiration function, enhanced saturation
      and oxygen tension in the arterial blood, arteriovenous oxygen difference, the
      rate and intensity of oxygen consumption in the tissues.

PMID- 22994059
TI  - [Rehabilitation of the patients presenting with oesophageal achalasia following
      balloon cardiodilation].
AB  - The present study involved a total of 25 patients presenting with oesophageal
      achalasia who had undergone balloon cardiodilation. The complex of rehabilitative
      measures concluded the application of an ultrahigh-frequency electromagnetic
      fields (decimeter wave (DMW) therapy) to the collar region and general iodine
      bromide baths. The treatment resulted in the elimination of dysphagia syndrome
      during consumption of solid food in 80% of the patients. Simultaneously, the
      oesophagogastroscopic study revealed the improvement of the state of oesophageal
      mucosa. Moreover, the thyrotropin level was normalized. The positive effect of
      such rehabilitative treatment persisted during 6-8 months.

PMID- 22994060
TI  - [The influence of procaine electrophoresis and mesotherapy on the characteristics
      of biological age].
AB  - The assessment of the biological age is needed to estimate the level of health
      and the efficacy of measures being undertaken to slow down the ageing processes
      and prolong the active life of the patients. Earlier studies have demonstrated
      the improvement of both physical health and psychic status of the elderly
      patients following intravenous administration of procaine. The objective of the
      present work was to evaluate effect of various methods of administration of a 2%
      procaine solution on the biological age. A total of 95 subjects at the age
      between 30 and 75 years were enrolled in the study. The procaine solutions were
      applied to the collar region. The patients of group 1 were treated with 2%
      procaine electrophoresis, those in group 2 with procaine galvanization with the
      same parameters. Mesotherapy using the 2% procaine solution was given to the
      patients of group 3. It was substituted by placebo (0.9% physiological solution)
      in the patients of group 4 (controls). The study revealed the most significant
      decrease of the biological age (calculated as described by L. M. Belozerova) in
      the patients treated with procaine electrophoresis (91% improvement). The
      mesotherapeutic administration of procaine also produced the beneficial effect
      (59% improvement). Neither procaine galvanization nor placebo mesotherapy caused
      any significant change of the variables characterizing the biological age.

PMID- 22994061
TI  - [The efficacy of polychromatic visible and infrared radiation used for the
      postoperative immunological rehabilitation of patients with breast cancer].
AB  - The immunological rehabilitation of the patients with oncological problems after
      the completion of standard anti-tumour therapy remains a topical problem in
      modern medicine. The up-to-date phototherapeutic methods find the increasingly
      wider application for the treatment of such patients including the use of
      monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers
      and photodiodes. The objective of the present study was to substantiate the
      expediency of postoperative immune rehabilitation of the patients with breast
      cancer (BC) by means of irradiation of the body surface with polychromatic
      visible (pVIS) in combination with polychromatic infrared (pIR) light similar to
      the natural solar radiation without its minor UV component. The study included 19
      patients with stage I--II BC at the mean age of 54.0 +/- 4.28 years having the
      infiltrative-ductal form of the tumour who had undergone mastectomy. These
      patients were randomly allocated to two groups, one given the standard course of
      postoperative rehabilitation (control), the other (study group) additionally
      treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1
      to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used
      for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter
      of 15 cm). The modern standard immunological methods were employed. It was found
      that mastectomy induced changes of many characteristics of cellular and humoral
      immunity; many of them in different patients were oppositely directed. These
      changes were apparent within the first 7 days postoperatively. The course of
      phototherapy (PT) was shown to prevent the postoperative decrease in the counts
      of monocytes and natural killer (NK) cells, the total amount of CD3+ -T
      lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells)
      and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted
      bacteria. Moreover PT promoted faster normalization of postoperative leukocytosis
      and activation of cytotoxic CD8+ -T-LPC, reduced the elevated concentration of
      immune complexes in blood. Among the six tested cytokines, viz. IL-1beta, TNF
      alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma, only the latter two underwent
      significant elevation of their blood concentrations (IL-6 within 1 day) and IFN
      gamma (within 7 days after mastectomy). The course of PT resulted in the decrease
      of their levels to the initial values. The follow-up of the treated patients
      during 4 years revealed neither recurrence of the disease nor the appearance of
      metastases.

PMID- 22994062
TI  - [The methods of phototherapy for the treatment and prevention of chronic
      dermatoses].
AB  - This paper reports the results of the treatment of 70 patients presenting with
      atopic dermatitis using a variant of phototherapy (polarized light generated by
      Bioptron-2 and Bioptron compact medical lamps). The efficacy of the treatment was
      estimated based on the dynamics of the skin conditions and variations of the
      dermatological index of the quality of life.

PMID- 22994063
TI  - [The organization of comprehensive rehabilitation of the children presenting with
      inflammatory intestinal diseases and celiacia under the conditions of a health
      resort].
AB  - In this study we report the experience with the provision of rehabilitative
      services for the children presenting with long-standing chronic diseases of the
      digestive organs (ulcerative colitis, Crohn's disease, celiac disease) based at a
      regional health resort. The possibility of comprehensive rehabilitation was
      substantiated with the contribution by non-medical specialists including a
      psychologist, social worker, and educator. A number of organizational problems
      related to rehabilitation logistics and scientific support have been successfully
      solved. Standard programs comprising the mechanisms of comprehensive
      rehabilitation and methods for the evaluation of its effectiveness are proposed.

PMID- 22994064
TI  - [The application of drinking mineral water in combination with zinc and silicon
      in rats undergoing immobilization stress].
AB  - The experiments carried out on male rats have demonstrated that the primary
      prophylactic application of drinking sulfate mineral water (MW) in combination
      with such microelements as zinc and silicon results in a more pronounced decrease
      of the magnitude of alterations in the liver, thymus, and blood hormonal spectrum
      under the action of immobilization stress than the application of mineral water
      alone. This effect is believed to be due to the activation of the organisms'
      adaptive reactions that enhances its resistance to stress.

PMID- 22994065
TI  - [The influence of ultrahigh-frequency electromagnetic radiation and low-intensity
      laser radiation on the body core temperature and basal metabolism in rats with
      systemic inflammation].
AB  - The effects of ultrahigh-frequency electromagnetic radiation (UHF EMR) and low
      intensity laser irradiation (LILI) on the body and skin temperature, oxygen
      consumption, production of carbon dioxide and heat release were investigated in
      the experiments on intact rats and during LPS-induced polyphasic fever. It was
      found that UHF EMR with the wavelength of 4,9 mm, 5,6 mm or 7,1 mm and LILI with
      the wavelength of 0.47 microm, 0.67 microm and 0.87 microm caused modulation of
      basal metabolism and thermal response to systemically administered
      lipopolysaccharide (LPS). These findings suggest that the most pronounced
      antipyretic and hypometabolic effects were observed after the treatment with UHF
      EMR at 7,1 mm and LILI at 470 microm.

PMID- 22994066
TI  - [The organization of provision of spa-and-resort services for the population of
      the russian Federation (part 2). Spa and resort institutions].
AB  - The main principles of the organization of medical activities of spa and resort
      institutions including children's and tuberculosis (phtysiatric) ones are
      discussed in conjunction with the relative normative and legal acts.

PMID- 22994067
TI  - [The health improving technologies in pediatrics].
AB  - The development of prophylactic treatment is one of most challenging and socially
      significant aspects of modern pediatrics. Today, a great variety of natural and
      artificial physical factors are employed to protect and/or restore the health of
      the children and to improve it. The broad scope of non-medicamentous technologies
      used for the purpose makes it possible to elaborate prophylactic programs adapted
      to the specific requirements of individual patients at all levels of medical care
      including therapeutic and prophylactic, spa and resort institutions, educational
      institutions, health improvement and recreational camps of different types, and
      home care.

PMID- 22994068
TI  - [How the "Kavkazskaya Riviera" health resort, Sochi, was restored. 1924].

PMID- 22994069
TI  - [How to increase the visibility of your scientific publication on the Internet?].
AB  - New technologies compel the scientists to change their thinking about
      dissemination of their own publications. In the time of rapid information
      exchange scientific papers should be available to the largest possible audience,
      it is therefore of vital importance to prepare them properly. The authors present
      the ways how to optimize the visibility of scientific publications on the
      Internet by the use of appropriate choice of words in the title, summary and key
      words. They discuss the mechanisms of indexing in scientific search engines and
      bibliographic-abstract databases showing at the same time how to use them in
      drawing up the paper. They also give an example of two summaries of the same
      article. The first one comprises the elements of academic search engine
      optimization (ASEO) while the other one does not follow these principles in the
      article description.

PMID- 22994070
TI  - Exposure to harmful microbiological agents during the handling of biomass for
      power production purposes.
AB  - BACKGROUND: Despite numerous benefits related to the utilization of biomass as an
      alternative source of energy, the handling of biomass creates a risk for the
      power industry workers of exposure to harmful microbiological agents. The purpose
      of this study was to evaluate the exposure of the workers to such agents at a
      power plant co-firing biomass with coal. This assessment was based on
      quantitative and qualitative characteristics of bioaerosols, supplemented with
      the analysis of biomass samples. MATERIAL AND METHODS: Air samples were collected
      with both MAS and Andersen six-stage impactors. Two different kinds of biomass
      samples used in the co-firing technological process were collected: sunflower
      seed peel pellet and wood chips. Bacterial and fungal concentrations were
      assessed in the air and biomass samples, and isolated microbial colonies were
      identified to the genus and/or species level. RESULTS: Bacterial and fungal
      concentrations at workplaces ranged between 5.1 x 10(2) cfu/m3 and 2.0 x 10(4)
      cfu/m3, and between 2.2 x 10(2) cfu/m3 and 2.3 x 10(4) cfu/m3, respectively. The
      highest concentrations were determined at workplaces related to reloading,
      screening and biomass transport via conveyor belts to silos. Fungi representing
      the genus Aspergillus, including A. fumigatus, A. niger, A. flavus and Gram
      negative rods of the genus Citrobacter, Pseudomonas and Rahnella prevailed in the
      air at all investigated workplaces. Bacterial and fungal concentrations in
      biomass samples amounted to 1.8 x 10(6) cfu/g and 1.1 x10(6) cfu/g, respectively.
      The qualitative analysis revealed that the composition of species in the biomass
      samples was similar to that observed in the air at workplaces. CONCLUSIONS:
      Workers engaged in the biomass combustion technology are exposed to bioaerosol
      containing potentially pathogenic bacteria and fungi.

PMID- 22994071
TI  - [Influence of classrooms acoustics on the teachers' voice sound pressure level].
AB  - BACKGROUND: Despite recent decreases in the number of registered cases of chronic
      disease of vocal mechanism, this disorder is still at the forefront of all
      occupational diseases in Poland. Most of the cases are observed in the Section of
      Education. Acoustic conditions in classrooms are often thought to be one of the
      causes of voice disorders. The aim of this study was to examine how the acoustics
      of classrooms affects the sound pressure of teachers' voice. MATERIAL AND
      METHODS: The acoustic properties of 21 classrooms in primary schools were studied
      as regards the working conditions of teachers' voice. The classrooms were divided
      into two groups: classes 0-III and classes IV-VI. Measurements of acoustic
      properties were performed according to PN-EN ISO 3382-1:2009, and measurements of
      sound pressure levels in the classrooms according to the Hodgson method. To study
      the relationship between the variables Spearman's rank correlation analysis was
      used. RESULTS: The study revealed a statistically significant relationship
      between the classroom acoustics and the students' activity (correlation
      coefficient, 0.86). It was also shown that the students' activity directly
      affected the level of teachers' voice (correlation coefficient, 0.68). In only
      24% of classrooms SPL of teachers' voice corresponded with the level of normal
      speech. CONCLUSIONS: The SPL of teachers' voice is influenced by a number of
      factors, including background noise and indirectly the classroom acoustics. One
      of the possibilities to improve working conditions of teachers is to create a
      suitable acoustic climate in the workplace, through acoustic treatment or
      changing equipment.

PMID- 22994072
TI  - [Assessment of hazards posed by metallo-organic compounds :' in industrial
      production and processing of polyvinyl chloride].
AB  - BACKGROUND: In Poland, the production and processing of polyvinyl chloride (PVC)
      are a significant part of industrial output. Yearly over 400 thousand tons of
      pure PVC are manufactured. Workers in the PVC industry are exposed to several
      organic compounds, including organic compounds of tin, barium, calcium, zinc and
      lead that are used as PVC stabilizers. In Poland there has been no research on
      the hazard posed by metallo-organic compounds in the work environment. MATERIAL
      AND METHODS: Twenty-two workstations in five industrial plants were studied. Air
      was sampled with a sampler that absorbed organometallic compounds. The metallo
      organic compounds were determined as metals, tin, lead, barium, with atomic
      absorption spectrometry (AAS) with electro-thermal atomization (ET-AAS). Calcium
      and zinc were determined with flame atomization (F-AAS). RESULTS: The highest
      concentrations of lead and tin were found in processes of preparing plastic,
      e.g., when backfilling surplus of weight stabilizers were weighed. High
      concentrations of tin were also found in processing plastic mixtures, e.g.,
      during foil calending. The lowest concentration of metallo-organic compounds was
      found in extrusion molding and in injection molding in PVC finishing.
      CONCLUSIONS: The concentration of metallo-organic compounds varied at the studied
      workstations. At some it was high--exceeding standard values, whereas at others
      it was low and the workers were not at risk. The emission of organic metallic
      compounds significantly depends on the process, the form of the stabilizers and
      the intensity of work. Thus it is necessary to check the levels of the
      concentration of those compounds at workstations.

PMID- 22994073
TI  - [Analysis of job retraining rulings issued by evaluating doctors and medical
      comissions of the social insurance institution].
AB  - BACKGROUND: Training pension was introduced into the Polish social security
      system on September 1, 1997. It is granted to a person who has permanently lost
      the ability to work in his or her current vocation, but after an appropriate
      retraining may do another profession. The aim of this study was to assess the
      compatibility between ruling of job retraining and medical certification rules.
      An effort was also made to evaluate the "effectiveness" of issued recommendations
      expressed by the number of retrained people. MATERIAL AND METHODS: In total, 300
      cases of retraining ruling issued by an evaluating doctor or medical commission,
      registered in 2009, were analyzed. Retraining pension was granted to 219 persons.
      RESULTS: Of the 300 rulings under study, over 35% were found groundless. In 52
      cases (23.74%) (219 of them were awarded a retraining pension) there is
      information about completed retraining (training) and in 24 (10.95%) about
      referral to a specific course and its duration, but there is no information
      whether the insured person has completed the training course. In 2 (0.91%) cases
      the insured persons continued to collect retraining pension (from 21 and 30
      months). 141 people were not retrained even though they had been granted a
      training pension. CONCLUSIONS: A significant percentage (over 35%) of rulings
      were issued improperly. It is caused by the ignorance of the rules of medical
      certification and binding regulations in this area. The number of training
      courses on the principles of issuing retraining rulings and current laws should
      be increased.

PMID- 22994074
TI  - [Occupational HBV and HCV infections among health care workers].
AB  - BACKGROUND: Analysis of the number of reported occupational hepatitis cases in
      the years 1971-2009 reveals a clear upward trend in the late 1980's, followed by
      a downward trend that has continued to the present. The aim of this study was to
      determine the number of recorded occupational hepatitis B and C in the Pomorskie
      voivodeship in the years 1999-2009 by the type and location of health care
      institutions and workpost category. MATERIALS AND METHODS: To analyze the
      epidemiological situation of occupational hepatitis among health care workers in
      the Pomorskie voivodeship, the data from 338 occupational disease certificates
      were obtained. RESULTS: In the period under study 341 cases of occupational
      hepatitis B and C (hepatitis B, 229; hepatitis C 112) were recorded in the
      province of Pomerania. The number of occupational hepatitis B decreased by 96.6%
      in the years 1999-2009, and hepatitis C by 90.5% in the years 2000-2009. The
      majority of infections occurred in large cities (Gdansk, Gdynia and Slupsk). The
      total number of cases included 301 (89%) women and 37 (11%) men. The largest
      number of infections was observed among nurses and midwives (155 and 10 cases,
      respectively). Definitely the highest incidence was observed in hospitals (230
      cases), analytical laboratories (42 cases), medical and dental clinics (20
      cases). CONCLUSIONS: The obtained data show a significant decrease in the
      incidence of occupational hepatitis during the discussed period. The highest
      number of infections was found among employees of hospitals and laboratories. A
      high number of cases in a small occupational group, employees of analytical
      laboratories, attracted our attention.

PMID- 22994075
TI  - [Evaluation of activities targeted at employability of older workers in Polish
      enterprises].
AB  - BACKGROUND: The article presents the results of evaluation of activities for
      older workers (50+) undertaken by Polish small, medium and large enterprises.
      MATERIAL AND METHODS: Data are derived from the questionnaire survey conducted on
      a nationwide sample of 200 small (9-49 employees), medium (50-249 employees) and
      large (> 250 employees) companies. RESULTS: In the total number of persons
      employed in the surveyed companies there were 27% of older workers. Special
      programs aimed at employing people aged over 50 were implemented in only less
      than 10% of the enterprises. In less than 18% of the companies employees 50+ were
      offered training/courses/conferences, addressed specially to them. In only 7% of
      companies counseling on healthy lifestyle was provided. For the companies
      surveyed, the most important benefit of hiring workers 50+ was the transfer of
      knowledge to young workers (86%). CONCLUSION: Due to the low employment rate of
      employees over 50, it is necessary to implement the principles of age management
      in companies, especially in medium and large ones. It is alarming that only less
      than 7% of the enterprises provide counseling on health care. In terms of ability
      to work and extending working life, such activities should be conducted on a
      large scale among workers of all ages, with particular emphasis on the elderly.

PMID- 22994076
TI  - [Polybrominated diphenyl ethers: sources of exposure and expected health
      effects].
AB  - Polybrominated diphenyl ethers (PBDE) along with hexabromocyclododecan,
      tetrabromobisphenol A and polybrominated biphenyls have been widely used for
      several decades as flame retardants. They have been added to consumer products,
      such as car and furniture upholstery, TV sets and computers. PBDE are not
      chemically bound to the polymers therefore, they can leach into the environment.
      They have been found in household dust, food, human breast milk, human adipose
      tissue and human serum. In this paper the potential major sources of emission of
      PBDEs, human biomonitoring data and results of experimental studies are reviewed.
      The available data shows that this group of compounds requires a particular
      concern because of their possibly adverse effects on human health and the
      environment.

PMID- 22994077
TI  - [Challenges for smoking cessation interventions targeted at women in Poland].
AB  - The paper addresses the problem of smoking among women. Based on the literature
      review of research conducted on large representative samples of Poles to define
      the range of this unhealthy behavior and its gender differences, the groups of
      Polish women who should especially become the target of smoking cessation
      interventions were identified. Furthermore, an attempt was made to characterize
      factors contributing to the initiation and continuation of tobacco smoking among
      adult women and the specificity of this unhealthy habit among those planning a
      pregnancy and expecting mothers. This information was based on the outcomes
      reported in the available literature on this issue. Finally, the guidelines for
      organizing smoking cessation interventions targeted at women in Poland are
      provided.

PMID- 22994078
TI  - [Borreliosis in occupational medicine practice].
AB  - Lyme borreliosis is a multisystem infectious disease that can occur from bites by
      infected ticks. It can appear at persons exposed professionally for staying in
      tick feeding environment as well as persons staying in such an environment
      occasionally. For a few years the Lyme disease is taking the leading place
      amongst occupational diseases and first amongst infectious occupational diseases.
      Lyme disease is a major problem especially in wooded areas of Poland however it
      can occur throughout the country. The variety of clinical and serological
      pictures is creating everyday diagnostic problems. The aim of this publication is
      to collect, methodize and remind the medical knowledge about pathogenesis,
      symptoms, diagnostics, prevention and medical certification of this disease.
      Disease symptoms were specified to appearing in various organs and systems in
      order to clarify this difficult to diagnose disease. Diagnostics of Lyme disease
      was divided into standard and highly specialized, performed in special cases.

PMID- 22994079
TI  - [Adaptation of the working environment to the capacities of workers with
      physical, intellectual and mental disabilities].
AB  - The occupational activity index among people with disabilities in Poland is still
      one of the lowest in Europe. Employers' resistance to employ these people is
      considered to be one of its major reasons. It stems from employers' fear of their
      low productivity and the need to adapt the work environment to their
      psychophysical capacities. In addition, the existing system of medical
      certification of disability does not motivate employers strong enough to adjust
      the work environment. This paper attempts to specify the main principles of the
      work environment adaptation to psychophysical capacities of two categories of
      workers with disabilities: those with motor function disabilities and those with
      intellectual or mental disability. For the former group of workers, the work
      environment adaptation may involve modifications of its physical aspects and
      entail some outlays, while for the latter group, the work environment adaptation
      is mainly based on the provision of workers with social support (both
      instrumental and emotional) by their supervisors and co-workers. Efforts
      associated with the work environment adaptation to the needs of workers with
      disabilities should, therefore, be considered not only in terms of outlays and
      enterprise productivity but also in terms of preventing social exclusion of
      people with disabilities.

PMID- 22994080
TI  - [Benzimidazole and its derivatives--from fungicides to designer drugs. A new
      occupational and environmental hazards].
AB  - Benzimidazole and benzimidazole derivatives play an important role in controlling
      various fungal pathogens. The benzimidazoles are also used to treat nematode and
      trematode infections in humans and animals. It acts by binding to the
      microtubules and stopping hyphal growth. It also binds to the spindle
      microtubules and blocks nuclear division. The most popular fungicide is
      carbendazim. The fungicide is used to control plant diseases in cereals and
      fruits. Laboratory studies have shown that carbendazim cause infertility and
      destroy the testicles of laboratory animals. Other benzimidazole derivatives are
      used as a preservative in paint, textile, papermaking, leather industry, and
      warehousing practices, as well as a preservative of fruits. Occupational exposure
      to benzimidazole may occur through inhalation and dermal contact with those
      compounds at workplaces where benzimidazole is used or produced. Some of the
      benzimidazoles are common environmental pollutants. They are often found in food
      and fruit products. Some of the benzimidazoles, like a astemizole or esomeprazole
      have found applications in diverse therapeutical areas. Despite of the clear
      advantages afforded by the use of benzimidazole derivatives, they share a danger
      potential. The most hazardous, however, are new illegally synthesed psychoactive
      drugs known as designer drugs. Some of them, like nitazene, etonitazene or
      clonitazene belong to benzimidazole derivatives. Laboratory animal studies
      revealed that etonitazene produced very similar effects in central nervous system
      as those observed after morphine administration. Considering etonitazene's
      properties, it seems reasonable to expected that long-term exposure to other
      benzimidazole derivatives may result in drug abuse and development of drug
      dependence.

PMID- 22994081
TI  - [Pathogenetic treatment for chronic constipation].
AB  - The investigations conducted in the past decade have offered better insight into
      the basic mechanisms of chronic constipation (CC), among other things, its
      association with large bowel (LB) transit and anorectal function. Intestinal
      dyskinesia, slow transit of the intestinal contents (inert LB), and impaired
      defecation due to pelvic floor dyssynergia play a leading role in the
      pathogenesis of primary constipation. Its treatment should be similar to that for
      CC. Motility regulators correcting LB dyskinesia are given to treat functional
      constipation and constipation-predominant irritable bowel syndrome. Enteral pro
      kinetic agents are effective in treating the inert LB. The possibilities of
      biofeedback therapy should be used to treat dyssynergic defecation.

PMID- 22994082
TI  - [Optimization of cell therapy in patients with inflammatory bowel diseases].
AB  - AIM: To elaborate optimal cell culture administration regimens to enhance the
      efficiency of anti-inflammatory therapy for inflammatory bowel diseases. SUBJECTS
      AND METHODS: Three groups of patients with chronic continuous or chronic
      recurrent ulcerative colitis (UC) were formed according to the treatment option:
      1) 15 patients with UC, in whom mesenchymal stromal cells (MSC) were thrice
      administered for a month at a one-week interval; 2) 20 patients with UC who
      received MSC once; 3) 20 patients with UC who had standard anti-inflammatory
      therapy with 5-aminosalycilic acid (5-ASA) preparations and glucocorticosteroids
      (GCS). The clinical activity of UC was evaluated using the Rachmilewitz index;
      its endoscopic pattern was assessed with the Mayo index. UC histological
      specimens were scored using the Gebs scale. To ascertain the duration of
      remission, the authors used the Kaplan-Maier survival curve method and calculated
      relative risk (RR) and odds ratio with 95% confidence intervals. RESULTS:
      Following 12 months, allogeneic bone marrow (BM) MSC transplantation performed
      thrice during a month caused the greatest reduction in the Rachmilewitz clinical
      activity index, Mayo endoscopic activity index, and Gebs pathohistological index
      in patients with UC as compared to those who had underwent one transplantation or
      received 5-ASA preparations and GCS (p < 0.05). The duration of remission also
      depended on the chosen therapy option for UC and the frequency of cell culture
      administration: the longer duration was recorded in patients who were infused
      thrice with allogeneic BM MSC. CONCLUSION: In the patients who had undergone one
      MSC administration, the risk of recurrent UC was higher than in those who had
      received MSC thrice during a month (a 2-year follow-up) and comparable with the
      RR of recurrent UC in the patient receiving only 5-ASA preparations, GCS, and/or
      immunosuppressants.

PMID- 22994083
TI  - [Specific features of hypolipidemic therapy in patients with abdominal ischemic
      disease].
AB  - AIM: To evaluate the efficiency and safety of combined drug therapy incorporating
      Ursofalk (Dr Falk Pharma GmbH, Germany) and a low-dose statin on the clinical
      course of the disease and blood lipid composition parameters in high-risk
      patients with abdominal ischemic disease (AID) and hepatic ischemic steatosis
      resulting from atherosclerotic lesion of the abdominal aorta (AA) and its
      unpaired visceral branches (UVB). SUBJECTS AND METHODS: One hundred and thirty
      nine patients (95 (68.3%) men and 44 (31.7%) women, aged 18-87 years) with AID
      and ischemic hepatopathy were examined and treated. AID in the examinees was
      verified by color duplex scanning and computed tomographic angiography of AA UVB,
      as well as by X-ray contrast aortography. The patients were treated with Ursofalk
      10-15 mg/kg/day in combination with atorvastatin 10-20 mg/day. RESULTS: Due to
      the combination therapy, abdominal pains became less significant in the majority
      of patients and disappeared in some subjects. The same positive changes were also
      observed in the signs of intestinal dysfunction. There was an improvement in
      blood lipid composition parameters. No substantial weight changes were noted in
      the patients during the treatment. No adverse reactions occurred due to the
      combined use of Ursofalk and atorvastatin. CONCLUSION: It is reasonable to co
      administer urosofalk and statins as an agent of hypolipidemic therapy in patients
      with AID concurrent with disseminated atherosclerosis and dyslipidemia that is
      accompanied by fatty infiltration of the liver with elements of fibrosis in 90%
      of cases and that is a pre-stage of steatohepatitis.

PMID- 22994084
TI  - [The efficiency and safety of adalimumab treatment in patients with active
      rheumatoid arthritis unresponsive to standard therapy: Russian national study
      results].
AB  - AIM: To confirm the efficacy and safety of adalimumab (ADA) added to the standard
      antirheumatic therapy performed in patients with rheumatoid arthritis (RA) of
      moderate and high activities. SUBJECTS AND METHODS: The open-labeled multicenter
      study enrolled 100 adult patients (11 men, 89 women; mean age 50.9 +/- 11.1
      years) with active RA according to the ACR criteria (1987) despite their
      treatment with disease-modifying antirheumatic drugs, the average number of which
      in the history was 2.1 per man. At baseline, DAS28 CRP was as many as 6.2 +/-
      0.84 scores; C-reactive protein (CRP) was 37.1 +/- 34.7 mg/l. In accordance with
      the indications officially registered in the European Union and the Russian
      Federation, ADA was given in a dose of 40 mg 2 weeks. Before administration of
      the drug, every patient underwent screening examination for tuberculosis, which
      used a tuberculin test and chest X-ray. The screening covered a period of the
      treatment up to 24 weeks and its subsequent period within 70 days after
      administration of the last dose of ADA in order to study its safety. RESULTS:
      DAS28-CRP scores decreased from 6.14 +/- 0.86 (at baseline) to 3.39 +/- 1.1 (by
      the end of the study). At 12 weeks, 22% of the patients achieved a low RA
      activity (DAS28-CRP < or = 3.2 scores); 14% achieved clinical remission (DAS28
      CRP < or = 2.6 scores); at 24 weeks, these were 37 and 25% of the patients,
      respectively. There were differences in effectiveness in terms of the baseline
      disease activity. At 24 weeks, ACR20, ACR50, and ACR 70 responses were achieved
      in 88, 67, and 26% of the patients, respectively. The HAQ functional index
      reduced from 1.9 +/- 0.6 (at baseline) to 1.081 +/- 0.64 (at 12 weeks) and 1.04
      +/- 0.68 (at 24 weeks) scores. Twenty-four patients were recorded as having 40
      adverse reactions (AR), including only one severe AR (septic arthritis). There
      were no cases of tuberculosis. CONCLUSION: The Russian multicenter study
      demonstrated the high clinical efficacy of ADA in patients with the moderate and
      high activity of RA unresponsive to standard therapy, as well as its satisfactory
      safety.

PMID- 22994085
TI  - [Markers of endothelial activation in rheumatoid arthritis].
AB  - AIM: To study relationships between endothelial activation parameters and
      inflammatory activity markers in patients with rheumatoid arthritis (RA).
      SUBJECTS AND METHODS: Fifty-three RA patients aged 19 to 62 years were examined.
      A control group comprised 28 apparently healthy individuals. The markers of
      endothelial activation, the parameters of RA activity, and their relationship
      were studied. RESULTS: There was an elevation in the level of interleukin-8 (IL
      8) to 413 (295; 547) pg/ml as compared to the control group 208 (207; 212) pg/ml.
      In the RA group, the concentration of soluble vascular cell adhesion molecule 1
      (sVCAM-1) increased up to 1929 (1297.6; 2739.6) ng/ml whereas in the control
      group it was 750 (734; 762) ng/ml (p < 0.001). In the patients with RA, the
      concentration of von Willebrand factor antigen (vWFAg) reached 1.4 (0.8; 1.9)
      IU/ml; in the control group, it was 0.6 (0.3; 0.8) IU/ml. In the RA group, the
      level of desquamated endotheliocytes (DE) was higher than that in the control
      group. Positive correlations were found between the markers of vascular
      endothelial activation and those of inflammation. There was a positive
      correlation between C-reactive protein (CRP), rheumatoid factor (RF), sVCAM-1,
      and DE. Significant positive correlations were observed between DAS28 and the
      inflammatory markers RF and CRP (R = 0.66; p < 0.05 and R = 0.4; p < 0.05) and
      the endothelial activation markers sVCAM-1 and vWFAg (R = 0.8; p < 0.05 and R =
      0.3; p < 0.05, respectively). CONCLUSION: The patients with RA had elevated IL-8,
      sVCAM-1, and vWFAg levels. Enhanced RA activity resulted in endothelial damage.

PMID- 22994086
TI  - [Efficiency of use of autologous activated serum in coxarthrosis].
AB  - AIM: To evaluate the clinical efficiency of using autologous conditioned
      (activated) serum (ACS) versus hyaluronic acid (HA) in coxarthrosis (CA).
      SUBJECTS AND METHODS: Two groups of patients (n = 54) who were matched for age,
      sex, and disease duration and had a valid diagnosis of CA were examined. During 3
      weeks, Groups 1 and 2 patients received intra-articular therapy with ACS or
      synocrome forte (Croma Pharma, Sotex), respectively, for 3 weeks. A 12-month
      follow-up evaluated the magnitude of pain, by using the visual analog scale (VAS,
      mm), the functional index WOMAC and general health, by applying the EQ-VAS scale.
      RESULTS: The only benefit of HA was found to be more functional improvement as
      detected by the WOMAC index (-21.8%; t = 2.56) at an early (1-month) follow-up.
      After 3 months, the patients in the ACS group were recorded to have the maximum
      VAS pain intensity reduction that was 76.5% greater than that (t = 4.31) in the
      HA group. The clearest advantages of ACS therapy were traced 6 months after
      treatment. CONCLUSION: The use of ACS may be a real alternative to that of HA
      derivatives in achieving good clinical outcomes in patients with CA. After ACS
      administration, there was a long-term preservation of achieved positive results.

PMID- 22994087
TI  - [Role of matrix metalloproteinase-9 in the pathogenesis of osteoporosis in
      patients with chronic obstructive pulmonary disease].
AB  - AIM: To determine a relationship between matrix metalloproteinase-9 (MMP-9)
      activity and its tissue inhibitors TIMP-1 and 2, tumor necrosis factor-alpha (TNF
      alpha), bone mineral density (BMD), and bone exchange in chronic obstructive
      pulmonary disease (COPD). SUBJECTS AND METHODS: Seventy-six patients with COPD
      and 20 healthy volunteers were examined using dual-energy X-ray absorptiometry n
      the lumbar spine (L(II)-L(IV)) and femoral neck (FN). The serum levels of MMP-9,
      TIMP-1 and TIMP-2, TNF-alpha, and beta-Crosslaps (betaCL) were measured. RESULTS:
      There was a higher MMP-9 level in COPD than that in the controls ((383.8 +/- 54.2
      and 137.6 +/- 31.4 pg/ml, respectively; p < 0.01). The levels of TIMP-1 and TIMP
      2 were not different from those in the control group. An inverse correlation was
      found between forced expiratory volume in one second (FEV1) and MMP-9
      concentration (r = -0.59; p = 0.002) and a positive correlation with smoking
      index (r = 0.47; p = 0.04). There was an inverse correlation between MMP-9
      concentration and BMD in both L(II)-L(IV) and FN (r = -0.67; p < 0.001 and r = 
      0.61; p < 0.01, respectively) and a direct correlation with betaCL (r = 0.53; p =
      0.04). An inverse correlation was established between TNF-alpha and T index in
      both L(II)-L(IV) (r = -0.54; p < 0.01) and FN (r = -0.48; p < 0.01). At the same
      time, the level of TNF-alpha directly correlated with the bone resorption marker
      betaCL (r = 0.53; p = 0.002) and MMP-9 (r = 0.57; p = 0.003). CONCLUSION:
      Elevated MMP-9 levels may play an important role in type I collagen degradation,
      giving rise to enhanced bone resorption in COPD.

PMID- 22994088
TI  - [Characteristics of the latent period of sensorimotor reactions in middle-aged
      and elderly outpatients with asthma during long-term treatment with inhaled
      glucocorticosteroids].
AB  - AIM: To study a relationship of the characteristics of simple and complex visual
      sensorimotor reactions to asthma controllability in middle-aged and elderly
      outpatients during disease-modifying antirheumatic drug therapy with
      beclomethasone, fluticasone, or budesonide in average and high daily doses.
      SUBJECTS AND METHODS: Eighty middle-aged and elderly patients with asthma were
      examined. The level of asthma control, the main parameters of external
      respiratory function, and the characteristics of simple and complex visual
      sensorimotor reactions were assessed. RESULTS: Uncontrolled asthma was observed
      in more than 50% of the asthmatic patients in the outpatient setting. Moderate
      linear relationships were found between the main physiological parameters and the
      level of the standard asthma control test. CONCLUSION: In the patients with
      controlled asthma, the latent periods of simple and complex visual sensorimotor
      reactions were significantly shorter than in those with poorly controlled asthma.

PMID- 22994089
TI  - [Outpatient evaluation of the immediate and delayed effects of the abnormally hot
      summer of 2010 on the course of cardiovascular disease].
AB  - AIM: To retrospectively evaluate the immediate and delayed effects of the
      abnormally hot summer of 2010 on the course of cardiovascular disease (CVD).
      SUBJECTS AND METHODS: The study enrolled 188 patients with CVD, who had visited a
      polyclinic for advice in the past 2 weeks of January 2011. In addition to general
      clinical examination, all the patients were proposed to fill out the Hospital
      Anxiety and Depression Scale questionnaires concerning their quality of life, by
      applying the visual analog scale during their visit and (retrospectively) in the
      abnormal hot period (AHP). The questions were concerned with the location of the
      patient during the heat wave, his/her health status, the duration of a working
      day, the number of hypertensive crises (HC), calls to medical emergency teams
      (MET), and visits to a doctor, the pattern of therapy, etc. The authors estimated
      the following outcomes (endpoints): acute myocardial infarction, acute
      cerebrovascular accident, admissions for CVD, MET calls, the number of disability
      days, HC, and unplanned visits to the doctor, which occurred during the heat wave
      or in the period September to December 2010. RESULTS: There was a worse quality
      of life during AHP. The patients living in the green zone (of a city, town, or a
      rural area) better experienced the abnormal heat. Male sex and overweight were
      associated with better abnormal heat tolerance; high anxiety, age, and living on
      high floors were with its worse tolerance. CONCLUSION: It is necessary to conduct
      large-scale prospective randomized studies, the results of which will yield
      objective information, which will be able to give patients scientifically sound
      recommendations how to behave during AHP.

PMID- 22994090
TI  - [Impact of cardiac resynchronization therapy on survival in patients with
      ischemic and nonischemic cardiomyopathy in clinical practice].
AB  - AIM: To compare the impact of cardiac resynchronization therapy (CRT) on survival
      in patients with ischemic and non-ischemic cardiomyopathy (CMP) in clinical
      practice. SUBJECTS AND METHODS: The study enrolled 206 patients with NYHA
      Functional Class II-IV chronic heart failure (CHF) and a left ventricular
      ejection fraction of < or = 35, including 107 patients implanted with CRT devices
      in combination with continuous drug therapy (DT). Among the 107 patients, 48 were
      diagnosed as having non-ischemic CMP (NCMP), 59 as coronary heart disease (CHD).
      The other 99 patients (12 with NCMP and 87 with CHD) were on DT only. Later on
      the patients from both groups were divided into subgroups according to the
      treatment policy of CHF: CRT + DT or DT only. The mean follow-up period was 24 +/
      18.1 months. RESULTS: The Kaplan-Meier survival analysis revealed that overall
      survival in the patients on CRT + DT was significantly higher than in those on DT
      (70 and 49%, respectively; p = 0.004). Analysis of the chosen treatment policy in
      the NCMP subgroup showed no significant differences in survival rates in the
      patients receiving CRT + DT or DT (74 versus 78%, respectively; p = 0.5). At the
      same time, the survival rates in the CHD patients on CRT + DT were significantly
      higher than those in the DT subgroup (68 versus 44%; p = 0.04). CONCLUSION: CRT
      significantly reduces overall mortality in patients with CHF in clinical
      practice. Our findings indicated that this effect was achieved mainly in patients
      with CHD, rather than in those with NCMP.

PMID- 22994091
TI  - [Long-term results of treatment for T-cell lymphoblastic lymphomas].
AB  - AIM: To define the efficiency of the GMALL 2002 program for the treatment of
      patients with T-cell lymphoblastic lymphomas (T-LBL). SUBJECTS AND METHODS:
      Twenty-five patients with a verified diagnosis of T-LBL were examined.
      Male/female ratio was 19:6; median age was 33 (range 16-67) years. There was a
      preponderance of patients with the generalized stages of the diseases: 2, 5, and
      18 with Stages II, III, and IV, respectively. Mediastinal lesion was found in 20
      (80%) of the 25 patients. Their treatment was performed according to the GMALL
      2002 program and similar CHOP courses. Analysis was made in 2 groups that were
      not different in their clinical and morphological characteristics. Group 1
      consisted of 17 of the 25 patients treated according to the GMALL programs; Group
      2 comprised 8 patients who had similar CHOP and other chemotherapy regimens.
      RESULTS: In Group 1, 15 (88%) patients achieved a complete clinical and
      hematological remission and 2 (12%) patients died in the first stages of the
      treatment. No relapses were noted. The median survival had not been achieved; 5
      year overall survival was 88 +/- 8%. In Group 2, three patients were alive; 2
      completed their treatment; 5 (63%) patients died from treatment failures. The
      median survival was 23 +/- 18%; 5-year overall survival was 45%. CONCLUSION: The
      findings suggest that the GMALL 2002 programs are highly effective in treating
      patients with T-LBL at the first stage of treatment.

PMID- 22994092
TI  - [Complex chromosome damages in patients with recurrent acute leukemias after
      allogeneic hematopoietic stem cell transplantations].
AB  - AIM: To study the pattern of complex chromosome damages (CCD) in acute leukemias
      (AL) and their place in the development of post-transplant recurrences (PTR) of
      AL. MATERIALS AND METHODS: Cytogenetic and partially molecular biological studies
      of bone marrow cells were conducted in 10 patients with PTR. Of them, 6 patients
      were diagnosed as having acute lymphoblastic leukemia (ALL), including T-ALL and
      Ph-positive ALL in 2 and 4 patients, respectively; and 4 patients had acute non
      lymphoblastic leukemia (ANLL), including one case secondarily induced by previous
      polychemotherapy (PCT) and irradiation. The standard G-band staining technique
      complemented by multicolor fluorescence in situ hybridization in one of the cases
      was used. RESULTS: It was shown that CCD had the similar pattern in 4 patients
      before transplantation and in PTR, progressed in 4 more patients, was absent or
      unnoticed in the early stage of the disease. The other recurrent chromosomal
      abnormalities that are worthy of notice are as follows: a) the presence of two Ph
      chromosomes in the cells of two of the 4 patients with Ph+ ALL; b) the frequent
      involvement of chromosome pairs 9, 19, 5, and 7 into the numerical and structural
      rearrangements. CONCLUSION: The important feature of PTR of AL is cellular CCDs,
      a portion of which is clearly related to previous PCT and may be of pathogenetic
      value for the development of recurrences.

PMID- 22994093
TI  - [Evaluation of the efficiency and safety of therapy with a combination of
      sulfonylurea derivatives and insulin sensitizers for type 2 diabetes mellitus].
AB  - AIM: To evaluate the efficiency and safety of early combination therapy with
      sulfonylurea derivatives (SUD) and insulin sensitizers in patients with type 2
      diabetes mellitus (T2DM). SUBJECTS AND METHODS: Forty patients (31 women and 9
      men; mean age 57.7 +/- 0.9 years) with decompensated T2DM (HbA(1c), 8.16 = +/-
      0.27%), a mean body mass index of 32.7 +/- 0.27 kg/m2, who received glimepiride,
      were examined. The duration of T2DM was 3.3 +/- 0.4 years. The patients had
      concomitant cardiovascular diseases (CVD). Coronary heart disease and
      hypertensive disease (HD) were treated; the doses of the agents were not adjusted
      during the study. For T2DM compensation, all the patients were given insulin
      sensitizers (rosiglitazone 4 mg) in addition to glimepiride. The treatment lasted
      24 weeks. Carbohydrate and lipid metabolic parameters, insulin resistance, body
      weight, structural and functional parameters, and heart rate were estimated
      before and after the treatment. RESULTS: During the combination therapy, there
      were decreases in the level of HbA(1c) from 8.16 +/- 0.27 to 6.84 +/- 0.15%,
      fasting blood glucose from 8.89 +/- 0.35 to 6.77 +/- 0.16 mmol/l, postprandial
      blood glucose from 8.66 +/- 0.24 to 7.761 +/- 0.20 mmol/l, HOMA index from 5.88
      +/- 0.70 to 3.75 +/- 0.44. The rate of hypoglycemic reaction reduced. Sugar
      lowering therapy was observed to have, on average, a positive impact on blood
      lipid composition and cardiovascular parameters in the group. Echocardiography
      (EchoCG) identified a group of patients with negative cardiac structural and
      functional changes. CONCLUSION: The combination therapy with SUD and insulin
      sensitizers was stated to be effective in maintaining the reached blood glucose
      level, reducing the risk of hypoglycemic reactions, and positively affecting
      lipid metabolism. The therapy resulted in cardiovascular improvement only in
      patients without obvious signs of CVD while it caused negative EchoCG changes
      (transformation of concentric to eccentric left ventricular hypertrophy) in
      patients with a long-term (more than 7 years) history of HD and pronounced
      cardiac structural and functional alterations.

PMID- 22994094
TI  - [Experience with ebrantil used in patients with resistant arterial hypertension
      in chronic kidney disease].
AB  - AIM: To evaluate the clinical efficacy of ebrantil used in patients with
      resistant arterial hypertension (RAH) in Stage III-V chronic kidney disease
      (CKD). SUBJECTS AND METHODS: Sixty-five patients with Stage III-V CKD and RAH
      (systolic blood pressure (SBP) 215.7 +/- 4.0 mm Hg and diastolic blood pressure
      (DBP) 114.6 +/- 2.3 mm Hg) were followed up. The patients received intravenous
      ebrantil (urapidil) in a dose of 25 mg for 5 days and then were switched to its
      oral use as 30-60-mg capsules twice daily for 12 weeks. RESULTS: The intravenous
      infusion caused a significant fall in SBP and DBP by 23.6 and 16.7%,
      respectively, within 60-90 min. A steady-state antihypertensive effect was
      achieved on days 5-7 (SBP and DBP was lowered to 146.8 +/- 6.1 and 95.6 +/- 5.3
      mm Hg, respectively; p < 0.05). After 12 weeks of the therapy, SBP was 144.4 +/-
      6.3 mm Hg and DBP was 93.3 +/- 4.1 mm Hg (p < 0.05). CONCLUSION: The use of
      ebrantil in patients with CKD and RAH produces an effective BP without marked
      adverse reactions.

PMID- 22994095
TI  - [Antidote therapy for acute carbon monoxide poisoning].
AB  - AIM: To evaluate the antidote properties of acizol in acute carbon monoxide
      poisoning (ACMP). SUBJECTS AND METHODS: The study included 70 patients with ACMP.
      Of them 35 patients received a package of medical measures, which involved 6%
      acizol solution injected in a dose of 1 ml on hospital admission and an hour
      later. The efficacy of acizol was evaluated using clinical and laboratory
      studies. RESULTS: Just an hour after acizol injection, there was an average 2
      fold reduction in the blood concentration of carboxyhemoglobin as compared to the
      baseline levels. Consciousness recovered 1.5 times more quickly than in the
      control group. The clinical efficacy of acizol was supported by positive
      laboratory tests. CONCLUSION: The use of acizol in ACMP assists in increasing the
      rate of detoxification and positively affects some blood laboratory parameters.

PMID- 22994096
TI  - [Single-photon emission computed tomography in the diagnosis of myocardial
      perfusion abnormalities in patients with rheumatoid arthritis: preliminary data].
AB  - Increased cardiovascular morbidity and mortality in patients with rheumatoid
      arthritis (RA) may be attributed to the fact that a systemic inflammation
      existing in this disease may trigger the development of atherosclerosis. 99mTC
      MIBI (4,2-methoxyisobutyl isonitrile) is a compound that permits myocardial
      perfusion to be visualized and has been proposed for the evaluation of the latter
      in patients with RA. Analysis of the results of the studies revealed transient
      myocardial ischemia areas in patients who did not take methotrexate while those
      who used it were found to have diminished perfusion areas that were, however,
      clinical insignificant.

PMID- 22994097
TI  - [Introduction to preventive and predictive medicine: past experience and future
      reality].
AB  - The active practical introduction of the achievements of genomics, proteomics,
      metabolomics, and bioinformatics brought about a fundamental change in views on
      the role and place of medicine in the structure of healthcare at the turn of the
      1980s-1990s, by giving impetus to the development of the radically new health
      care area--preventive, predictive, and personalized medicine (PPPM).

PMID- 22994098
TI  - [Primary sclerosing cholangitis: present views of its pathogenesis, diagnosis and
      treatment].
AB  - Primary sclerosing cholangitis (PSC) is a chronic slowly progressive cholestatic
      liver disease characterized by non-purulent destructive inflammation and
      sclerosis of the extra- and intrahepatic bile ducts, leading to secondary biliary
      cirrhosis. The etiology of the disease is unknown; however, bacterial and genetic
      factors are presumed to be implicated. In 66-84% of cases, PSC is accompanied by
      inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. The
      diagnosis of PSC is based on the clinical presentation of the disease and on the
      data of magnetic resonance imaging or endoscopic retrograde cholangiography. The
      treatment of PSC has not been developed; there is evidence that ursodeoxycholic
      acid reduces cholestasis. Orthotopic liver transplantation is indicated at the
      stage of decompensated liver cirrhosis.

PMID- 22994099
TI  - [Diabetes mellitus is an independent risk factor for cardiovascular disease].
AB  - Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the
      incidence of which tends to grow steadily. The great social importance of
      diabetes mellitus is determined by disability and deaths from late vascular
      events. So the risk for cardiovascular disease (CVD) and the cardiovascular
      safety of glucose-lowering therapy for T2DM are a multidisciplinary and multi
      faceted problem. Its solution requires a comprehensive approach to controlling
      the risk factors of CVD and assessing hypoglycemic therapy in the context of
      cardiovascular safety. The paper shows the bases of CVD pathogenesis and contains
      the results of numerous international clinical trials evaluating the efficiency
      and safety of current glucose-lowering therapy (metformin and cardioprotective
      drugs, the action of which is based on their incretin effect).

PMID- 22994100
TI  - [Cough: differential diagnosis and differentiated treatment].
AB  - The review presents an update on the determination of the causes and mechanisms
      of acute and chronic cough. It assesses the concept of productive and non
      productive cough (acute cough, chronic cough), its duration in different diseases
      of the lung, upper and lower respiratory tract, pulmonary embolism,
      gastroesophageal reflux disease, pharyngolaryngeal reflux, and during treatment
      with angiotensin-converting enzyme inhibitors. Information is given on treatment
      policy for cough in different diseases.

PMID- 22994101
TI  - [The results of up-to-date techniques of automated endothelial keratoplasty].
AB  - The results of different techniques of automated endothelial keratoplasty (EKP)
      performed in 72 patients with bullous keratopathy are estimated. Automated EKP
      with superficial flap was performed in 18 patients (1st group), Descemet
      stripping automated EKP (DSAEK) - in 26 patients (2nd group), Descemet stripping
      automated EKP (DSAEK) with thin grafts - in 20 patients (3rd group), Descemet
      membrane automated EKP with stromal rim (DMAEK) - in 8 patients (4th group).
      According to our results DSAEK with thin grafts is indicated to elderly patients
      with severe ocular disease (ocular comorbidities, repeated surgery, advanced
      keratopathy). DSAEK is a promising surgical technique allowing to achieve the
      best functional results. Nevertheless this procedure is technically challenging
      and is good for relatively functionally "preserved" patient groups.

PMID- 22994102
TI  - [Surgical treatment of advanced retinopathy of prematurity--last chance for
      vision. Report 1. Analysis of anatomic results].
AB  - Anatomic results of treatment of advanced retinopathy of prematurity (ROP) are
      analyzed between 2005 and 2010 in ophthalmologic department of city children's
      hospital ( St. Petersburg). 154 children (303 eyes) aged from 3 months till 1,5
      years were treated. Birthweight was 700-2590 g, gestational age was from 22-23
      till 33-34 weeks. 4B stage was diagnosed in 20 eyes (6,6%) and in the rest 283
      cases (93,4%) there was stage 5 ROP. Totally 646 operations were performed: 302
      lensvitrectomies (46,7%) and 344 vitrectomies (53,3%). Total retinal attachment
      was achieved in 28,1% (85 eyes), almost total (solitary folds remained) in 21,1 %
      (64 eyes), partial result (significant fold reduction with attached areas) was in
      17,8% (54 eyes) and in 33% (100 eyes) acceptable results were not achieved.

PMID- 22994103
TI  - [Surgical treatment of advanced retinopathy of prematurity--last chance for
      vision. Report 2. Analysis of functional results].
AB  - Functional results of staged surgical treatment of advanced retinopathy of
      prematurity (ROP) are analyzed between 2005 and 2010 in ophthalmologic department
      of city children's hospital ( St. Petersburg). A total of 154 children (303 eyes)
      were operated. The assessment of visual functions was performed using proposed
      original method. Subject vision was achieved in 65% of 20 eyes (6,6%) with 4B
      stage ROP. Fair anatomic results were achieved in 131 eyes of children with 5
      stage ROP (283 eyes), light perception was preserved in 52 eyes (39,7%),
      capability to distinguish large objects appeared in 40 eyes (30,5%) and subject
      vision developed in 39 eyes (29,8%). Correlation between visual functions and
      environmental conditions was found, in particular presence or absence of long
      term period of training in color and individual objects distinguishing. In a
      group of children training resulted in achievement of fair functions (subject
      vision, capability to distinguish large objects) in 81,2% of patients, where as
      in a group without training the same capabilities developed in 31,8% of cases
      only. Functional outcomes were also found to depend on CNS condition and time of
      surgery.

PMID- 22994104
TI  - [Markers of Fas-mediated apoptosis in primary open-angle glaucoma and
      opportunities of their pharmacological correction].
AB  - In order to assess the role of apoptosis in pathogenesis of primary open-angle
      glaucoma (POAG) apoptosis markers were studied in blood serum and tear fluid of
      patients with or suspected to have different stages glaucoma. To date the study
      of POAC pathogenesis goes along with search of possible ways of pharmacotherapy,
      neuroprotection is considered to be a promising option. Dynamics of sFas/Apo-1
      and sFasL as the markers of Fas-mediated apoptosis was studied during treatment.
      We used nootropic citicoline as a neuroprotector. The markers were studied using
      enzyme immunoassay. The results show association of POAG onset and progression
      with interruption of Fas-mediated apoptosis, indicated by the level and
      proportion of sFas/Apo-1 and sFasL in tear fluid and in a less degree in blood
      serum. Characteristic features are detected in Fas/FasL system associated with
      glaucoma stage and correlating with some clinical and functional parameters
      (perimetry) that is important for understanding of POAG pathogenesis and for
      prognosis of disease course.

PMID- 22994105
TI  - [Comparative analysis of morphometric optic nerve head parameters in patients
      with open-angle glaucoma according to optical coherence tomography and retinal
      tomography].
AB  - To date objective methods of optic nerve head (ONH) parameters examination such
      as optical coherence tomography (OCT) and Heidelberg retinal tomography (HRT) are
      of great importance. The goal of the study was to compare ONH parameters in
      patients with different stages of glaucoma. Analysis of obtained data showed
      inconsiderable difference in absolute parametric indices, this is explained by
      different principles of ONH borders detection (OCT - the margin of pigment
      epithelium layer, HRT - scleral rim) as well as subjectivity in contour
      detection. OCT and HRT data allow to assess glaucomatous optic neuropathy and can
      be used independently as well as in addition to each other. Spectral OCT provides
      earlier diagnosis of glaucomatous optic neuropathy compared with HRT.

PMID- 22994106
TI  - [The influence of water soluble antioxidant agent (mexidol) on optic nerve and
      blood flow velocity in ocular and orbital arteries in patients with primary open
      angle glaucoma].
AB  - The prospective single-blind placebo-controlled randomized trial is devoted to
      influence of mexidol (2-ethil-6-methil-3-hydroxipiridine succinate) on dynamics
      of optic nerve electrophysiologic profile and velocity indices of blood flow in
      ocular and orbital arteries in correlation with changes of retinal
      photosensitivity, visual acuity and visual field size during course of
      intravenous mexidol infusions and standard treatment of primary open-angle
      glaucoma. 2 weeks of intravenous infusions of 300 mg mexidol daily was found to
      cause depression of optic nerve electrical sensitivity threshold and widening of
      total visual field (16 mm2 test stimulus) after 14 days of treatment. These
      effects were not associated with changes of blood flow velocity in ocular and
      orbital arteries, were transient and came to initial indices 3 months after the
      end of treatment. Delayed vasotropic effect of mexidol manifested in increase of
      blood flow velocity in central retinal artery in 90 days after the end of
      infusions.

PMID- 22994108
TI  - [The effect of yellow filter intraocular lens on the macula after cataract
      phacoemulsification in patients with age macular degeneration].
AB  - Macula changes diagnosed with optical coherence tomography (OCT) within a year
      after cataract phacoemulsification (PE) with intraocular lens implantation with
      and without yellow filter are presented. 32 patients (36 eyes) with early stages
      of age macular degeneration (AMD) were included into the experimental group and
      35 patients (36 eyes) served as controls. IOLs with yellow filter were implanted
      in 21 eyes, and in 15 cases IOLs without filter were used in each group.
      According to OCT data thickening of fovea and increasing of macula volume
      developed within 6 months after cataract PE. Implantation of yellow filter IOLs
      reduced the intensity of these changes after surgery in patients with AMD. The
      progression of early AMD into advanced stages within a year after PE was not
      observed.

PMID- 22994107
TI  - [Pseudoexfoliation syndrome: pathogenesis of impairment of vegetative sympathetic
      innervation associated with cervical spine disorder].
AB  - The results of magnetic resonance imaging of the cervical spine in 33 patients
      with mono- and bilateral pseudoexfoliation syndrome (PES) and cervical
      osteochondrosis are presented. The protrusion of intervertebral discs localized
      in the site of ciliospinal center and rarer in the site of superior cervical
      sympathetic ganglion is found. The protrusion of intervertebral discs in patients
      with PES was associated with compression of spinal roots significantly more often
      than in patients with cataract and osteochondrosis but without PES (control
      group). The side of protrusion and compression of spinal roots corresponded to
      the side of PES in more than 50% of cases. Compressive disorders of cervical
      spinal structures may be of considerable importance in pathogenesis of PES.

PMID- 22994109
TI  - [Functional multi-detector computed tomography in diagnosis of orbital fractures.
      The first results].
AB  - The first results of use of functional multi-detector computed tomography in
      diagnosis of orbital fractures with eye movement impairment are obtained. In
      addition to orbital bone fractures diagnosis this method allows to perform more
      detailed evaluation of orbital soft tissues particularly extraocular muscles.
      Proposed method allows differentiating paralytic and restrictive ophthalmoplegia,
      evaluate the function of extraocular muscles in severe orbital deformities.

PMID- 22994110
TI  - [Morphogenesis of complications after long-term intraocular silicon oil filling
      (clinical histopathological study)].
AB  - The question of necessity and time of silicon oil (SO) removal after tamponade
      for traumatic retinal detachment (TRD) is still controversial. So the study of
      changes in the eye filled with SO for a long time is of great interest.
      Histopathologic analysis of 9 enucleated eyes filled with SO for TRD during long
      time period (from 6 months till 30 years) was performed. The characteristic
      change was inflammatory reaction with fibrin membranes surrounding silicon drops
      and development of proliferative vitreoretinopathy and tractional retinal
      detachment in the following. In 2 cases the inflammatory process around SO was
      associated with bone formation. The most severe complication was the imbibition
      of retina with SO in a vacuole-like manner associated with total atrophy of
      neural structures. Obtained data show that time for SO removal should be less
      than 6 months after surgery.

PMID- 22994112
TI  - [Optical coherence tomography in patients with foveal hypoplasia and high visual
      acuity].
AB  - Two clinical cases of children with foveal hypoplasia and high visual acuity
      examined using optical coherence tomography are presented. Genetic examination
      found oculocutaneous albinism type 1 in one patient. Potential causes and
      functional value of foveal hypoplasia are discussed.

PMID- 22994113
TI  - [Maturation and plasticity of visual system: neurogenesis, synaptogenesis, and
      myelogenesis. Report 2. Visual cortex and optic radiations].
AB  - Current conceptions of visual cortex synaptogenesis and mielination are reviewed.
      Human brain undergoes significant morphological and functional changes during
      prenatal period and the fist year of life that reflexes in height, latency and
      configuration of visual evoked potentials. The stages of neural modification are
      genetically predetermined, but it keeps developing under the influence of altered
      sensory experience. Period of accelerated development of nerve cells and
      formation of synaptic contacts is followed by global gradual elimination of
      exuberant neurons and their ineffective contacts, that promotes greater
      specificity of neuronal tissue and fine functional tuning. The importance of up
      to-date functional and morphometric methods of brain maturation and plasticity
      research such as diffuse tractography is emphasized.

PMID- 22994111
TI  - [Fibrinolysis components and angiogenesis regulation by example of burn-induced
      corneal neovascularization in rabbits].
AB  - Increased plasminogen level in tear fluid was found within 28 days and increased
      plasmin activity in 1-3 and 21 days after alkali burn of cornea, this is the time
      of cornel ulcers development. Increased plasminogen level and plasmin activity in
      cornea, conjunctiva and intraocular fluid was found in three days after trauma.
      Subconjunctival injections of angiostatin K1-4,5 (a product of plasminogen
      metabolism) during 3 weeks resulted in significant suppression of corneal
      neovascularization within 14 days and of active branching of the vessels in the
      following. The use of angiostatin reduced depth and area of corneal ulcers.
      Obtained data shows the promising potential of development of medications based
      on angiostatin K1-4,5 for suppression of corneal neovascularization and for
      treatment of diseases associated with corneal ulceration.

PMID- 22994114
TI  - [Safety aspect of age macular degeneration treatment].

PMID- 22994115
TI  - [Kallikrein-kinin system as a target for diabetic retinopathy treatment].
AB  - Multifactor etiology of diabetic retinopathy (DR) determines difficulty of
      understanding of pathogenesis and need of search of effective approaches to study
      key mechanisms of development of this microvascular complication of diabetes
      mellitus (DM). Significant achievements of the last years show the contribution
      of two proteolytic systems into pathogenesis of DR, that control vascular tone
      and permeability - kallikrein-kinin (KKS) and renin-angiotensin systems (RAS).
      Among new approaches to DR treatment one of the most appropriate is an influence
      on KKS by means of inhibiting kallikrein, that leads to reduction of retinal
      vascular permeability and allows to prevent the development of macula oedema and
      other consequences of vascular wall damage in DR.

PMID- 22994116
TI  - [Contribution of professor N.B. Shoulpina into national ophthalmological science
      (90 years of the birth)].

PMID- 22994117
TI  - [Maintaining competence in pediatric nursing].

PMID- 22994118
TI  - ["It is important to recognize warning signals" (interview by Christian
      Heinemeyer)].

PMID- 22994119
TI  - [Keeping the environment of the child in mind].

PMID- 22994120
TI  - [Support and encouragement].

PMID- 22994121
TI  - [Completing the troika for making decisions].

PMID- 22994122
TI  - [Creating the transition].

PMID- 22994123
TI  - [Laying the the cornerstone for postoperative success].

PMID- 22994124
TI  - [Thinking of personal needs].

PMID- 22994125
TI  - [Assessing and promoting the quality of life].

PMID- 22994126
TI  - [Child protection from the beginning. Need for early peripartum support -
      clinical experiences].
AB  - BACKGROUND: So called early interventions aim to promote healthy development and
      welfare of children and to prevent child maltreatment. For this purpose,
      psychosocial support measures offered during the perinatal phase are regarded to
      be highly promising. As part of a project located at an academic hospital, the
      significance of such early interventions during obstetric care was to be elicited
      from the clinicians' view. METHODS: Semi-structured interviews with 12 health
      care professionals from the maternity hospital unit (n = 8 nurses, n = 3
      midwifes, n = 1 medical doctor). RESULTS: Four main categories were identified:
      i) patient situations indicating need for early psychosocial support (precarious
      living circumstances, complicated pregnancy, and maternal psychiatric disorders),
      ii) detection of patients in need of this kind of support, iii) reacting to
      presumed or confirmed need for early psychosocial support, and iv) context
      factors impacting on clinicians' assessment and activities. The interviews
      revealed some room for improvement, e.g. with respect to identifying patients in
      need for early psychosocial support, communicating with them, and collaborating
      with communal health care and welfare institutions. CONCLUSIONS: In the
      clinicians' view, early psychosocial interventions appear to have an important
      role in hospital obstetric care. Based on results from this study, local care
      processes were adapted.

PMID- 22994127
TI  - [When students take over the pediatric department].

PMID- 22994128
TI  - [When technology outwits nature].

PMID- 22994129
TI  - [Resolving the legal status in a doubtful case before the court].

PMID- 22994130
TI  - [Fever, diarrhea, vomiting].

PMID- 22994131
TI  - [When something goes wrong...].

PMID- 22994132
TI  - [Wound dressing holds its own in the study and in general practice test].

PMID- 22994133
TI  - Bacteria-mediated arsenic oxidation and reduction in the growth media of arsenic
      hyperaccumulator Pteris vittata.
AB  - Microbes play an important role in arsenic transformation and cycling in the
      environment. Microbial arsenic oxidation and reduction were demonstrated in the
      growth media of arsenic hyperaccumulator Pteris vittata L. All arsenite (AsIII)
      at 0.1 mM in the media was oxidized after 48 h incubation. Oxidation was largely
      inhibited by antibiotics, indicating that bacteria played a dominant role. To
      identify AsIII oxidizing bacteria, degenerate primers were used to amplify ~500
      bp of the AsIII oxidase gene aioA (aroA) using DNA extracted from the media. One
      aioA (aroA)-like sequence (MG-1, tentatively identified as Acinetobacter sp.) was
      amplified, exhibiting 82% and 91% identity in terms of gene and deduced protein
      sequence to those from Acinetobacter sp. 33. In addition, four bacterial strains
      with different arsenic tolerance were isolated and identified as Comamonas sp.C
      1, Flavobacterium sp. C-2, Staphylococcus sp. C-3, and Pseudomonas sp. C-4 using
      carbon utilization, fatty acid profiles, and/or sequencing 16s rRNA gene. These
      isolates exhibited dual capacity for both AsV reduction and AsIII oxidation under
      ambient conditions. Arsenic-resistant bacteria with strong AsIII oxidizing
      ability may have potential to improve bioremediation of AsIII-contaminated water
      using P. vittata and/or other biochemical strategies.

PMID- 22994134
TI  - Molecularly imprinted hybrid adsorbents for adenine and adenosine-5'
      triphosphate.
AB  - Submicrometer-sized silica gel particles were coated with a polyanion and a
      polycation bearing thymine chromophores. The polymer-coated particles were found
      to selectively adsorb adenine and adenosine-5'-triphosphate (ATP), as compared to
      other nucleobases and nucleotides, respectively. The adsorption was enhanced by
      the irradiation of the particles in the presence of adenine which resulted in the
      molecular imprinting of adenine. ATP adsorption was strongly pH-dependent.

PMID- 22994135
TI  - Molecular characterization and phylogenetic analysis of Babesia sp. NV-1 detected
      from wild American Mink ( Neovison vison ) in Hokkaido, Japan.
AB  - Babesiosis is a tick-borne protozoan disease affecting many mammalian species
      worldwide, caused by the intraerythrocytic multiplication of Babesia spp. The
      present study aimed to detect the presence of Babesia sp. in 13 American mink
      from Hokkaido, Japan. One of 13 animals was positive, as indicated by nested PCR
      targeting the 18S ribosomal RNA (SSU rDNA) and subunit 7 (eta) of the chaperonin
      containing t-complex polypeptide 1 (CCT7) genes from species of Babesia and
      Theileria. Sequencing of the PCR product of SSU rDNA revealed 99% homology to the
      isolates of Babesia sp. SAP#131 found in raccoons in Hokkaido, whereas that of
      the CCT7 gene showed 80% homology to the isolates of Babesia gibsoni in dogs as
      determined by BLAST analysis. We refer to the cognate sequence as Babesia sp. NV
      1. Phylogenetic analyses of SSU rDNA and CCT7 genes from Babesia sp. NV-1
      revealed them to be most closely related to the Babesia sp. SAP#131 from a
      raccoon in Hokkaido and to canine B. gibsoni, respectively. Here, we provide the
      first molecular evidence of the Babesia sp. NV-1 parasite in feral American mink
      ( Neovison vison ) in Hokkaido, Japan.

PMID- 22994136
TI  - The Frailty Instrument for primary care of the Survey of Health, Ageing and
      Retirement in Europe predicts mortality similarly to a frailty index based on
      comprehensive geriatric assessment.
AB  - AIM: Frailty is an emerging concept in primary care, which potentially can
      provide healthcare commissioners with a clinical focus for targeting resources at
      an aging population. However, primary care practitioners need valid instruments
      that are easy to use. With that purpose in mind, we created a Frailty Instrument
      (FIt) for primary care based on the Survey of Health, Aging and Retirement in
      Europe (SHARE). The aim of the present study was to compare the mortality
      prediction of the five-item SHARE-FIt with that of a 40-item Frailty Index (FIx)
      based on comprehensive geriatric assessment (CGA). METHODS: The participants were
      15,578 women and 12,783 men from the first wave of SHARE. A correspondence
      analysis was used to assess the degree of agreement between phenotypic
      classifications. The ability of the continuous frailty measures (FIt score and
      FIx) to predict mortality (mean follow up of 2.4 years) was compared using
      receiver-operating characteristic (ROC) plots and areas under the curve (AUC).
      RESULTS: In both sexes, there was significant correspondence between phenotypic
      categories. The two continuous measures performed equally well as mortality
      predictors (women: AUC-FIx = 0.79, 95% CI 0.75-0.82, P < 0.001; AUC-FIt = 0.77,
      95% CI 0.73-0.81, P < 0.001; men: AUC-FIx = 0.77, 95% CI 0.74-0.79, P < 0.001;
      AUC-FIt = 0.76, 95% CI 0.74-0.79, P < 0.001). Their equivalent performance was
      confirmed by statistical comparisons of the AUC. CONCLUSIONS: SHARE-FIt is
      simpler and more usable, and predicts mortality similarly to a more complex FIx
      based on CGA.

PMID- 22994137
TI  - Direct ion speciation analysis with ion-selective membranes operated in a
      sequential potentiometric/time resolved chronopotentiometric sensing mode.
AB  - Ion-selective membranes based on porous polypropylene membranes doped with an
      ionophore and a lipophilic cation-exchanger are used here in a new tandem
      measurement mode that combines dynamic electrochemistry and zero current
      potentiometry into a single protocol. Open circuit potential measurements yield
      near-nernstian response slopes in complete analogy to established ion-selective
      electrode methodology. Such measurements are well established to give direct
      information on the so-called free ion concentration (strictly, activity) in the
      sample. The same membrane is here also operated in a constant current mode, in
      which the localized ion depletion at a transition time is visualized by
      chronopotentiometry. This dynamic electrochemistry methodology gives information
      on the labile ion concentration in the sample. The sequential protocol is
      established on potassium and calcium ion-selective membranes. An increase of the
      ionophore concentration in the membrane to 180 mM makes it possible to determine
      calcium concentrations as high as 3 mM by chronopotentiometry, thereby making it
      possible to directly detect total calcium in undiluted blood samples. Recovery
      times after current perturbation depend on the current amplitude but can be kept
      to below 1 min for the polypropylene based ion-selective membranes studied here.
      Plasticized PVC as membrane material is less suited for this protocol, especially
      when the measurement at elevated concentrations is desired. An analysis of
      current amplitudes, transition times, and concentrations shows that the data are
      described by the Sand equation and that migration effects are insignificant. A
      numerical model describes the experimental findings with good agreement and gives
      guidance on the required selectivity in order to observe a well-resolved
      transition time and on the expected errors due to insufficient selectivity. The
      simulations suggest that the methodology compares well to that of open circuit
      potentiometry, despite giving complementary information about the sample. The
      tandem methodology is demonstrated in a titration of calcium with
      nitrilotriacetic acid (NTA) and in the direct detection of calcium in undiluted
      heparinized and citrated blood.

PMID- 22994138
TI  - Comparison of changes in facial skin temperature caused by ethyl chloride
      spraying, ice block rubbing and cold gel packing in healthy subjects.
AB  - The aim of this study was to compare the effects of three cryotherapeutic
      modalities (ethyl chloride spraying, ice block rubbing and cold gel packing) on
      facial skin temperature. Thirty healthy volunteers (15 men, 15 women; mean age,
      29.4 +/- 3.2 years) participated in this study. Each of the three modalities was
      randomly applied to the skin over the right masseter muscle. The skin surface
      temperature was recorded at baseline and every 5 min for 60 min after the
      application of one of the three cryotherapeutic modalities. Immediately after
      application, cold gel packing demonstrated the greatest reduction in surface
      temperature (10.6  degrees C), followed by ethyl chloride spraying (4.3  degrees
      C) and ice block rubbing (3.7  degrees C) (P < 0.001). During the 60-min post
      application period, ethyl chloride spraying and ice block rubbing produced
      similar skin surface temperature changes. The skin surface remained coldest for
      the longest period of time after cold gel packing. The median time for recovery
      of the baseline temperature after application of the cold gel pack was about
      three to four times longer than that for the other modalities (P < 0.001). Ethyl
      chloride spraying and ice block rubbing resulted in less reduction and faster
      recovery of skin surface temperature than did cold gel packing. In conclusion,
      ethyl chloride spraying and ice block rubbing had a limited cooling effect on the
      facial skin tissue and could not reduce the skin surface temperature enough for
      local analgesia. Moreover, the cooling effect of cold gel packing was remarkable,
      but not sufficient for local analgesia.

PMID- 22994139
TI  - Microscopic investigation on morphologies of bilayer gel structure in the mixed
      polyoxyethylene-type nonionic surfactant systems.
AB  - We investigated morphologies of lamellar domains below the Krafft temperature in
      the mixed polyoxyethylene-type nonionic surfactant, a C(16)E(6)/C(16)E(7)/water
      system, by using optical microscopy, confocal microscopy, small/wide-angle X-ray
      scattering, and small-angle neutron scattering. We have found that the morphology
      discontinuously changes from network structures of lamellar domains to spherical
      vesicles with increasing mole fraction of C(16)E(7), via the coexistence region
      of vesicles and network structures of lamellar domains.

PMID- 22994140
TI  - Inhibition of ocular neovascularization by a novel peptide derived from human
      placenta growth factor-1.
AB  - PURPOSE: To evaluate the effect of ZY1, a novel 21-amino acid peptide from human
      placenta growth factor-1 (PlGF-1), against ocular neovascularization, and to
      study its possible toxicity to the retina and the underlying mechanism of
      antiangiogenic effect. METHODS: MTS assays, a modified Boyden chamber and
      Matrigel(TM) were used to evaluate the effect of ZY1 on the proliferation,
      migration and tube formation of RF/6A rhesus macaque choroid-retina endothelial
      cells induced by vascular endothelial growth factor (VEGF) in vitro. The
      antiangiogenic effect of ZY1 was also studied with corneal micropocket
      angiogenesis assays and oxygen-induced retinopathy (OIR) assays in mice.
      Electrophysiological tests and histological examinations were used to study the
      possible toxicity of ZY1 against mouse neuroretina. Competitive ELISA and Western
      blotting were performed to elucidate the underlying mechanism of ZY1. RESULTS:
      ZY1 inhibited VEGF-induced RF/6A proliferation, migration and tube formation. It
      also inhibited ocular neovascularization when applied to the corneal micropocket
      angiogenesis assays and OIR assays in mice. Electrophysiological tests and
      histological examinations revealed no evident functional or morphologic
      abnormalities in mouse neuroretina after ZY1 injection. ZY1 competed for binding
      to VEGFR-1 against PlGF and VEGF and inhibited VEGFR-1/ERK/AKT activation.
      CONCLUSION:  It is concluded that the novel peptide ZY1 is an effective inhibitor
      of ocular pathologic angiogenesis and may provide a promising alternative for
      ocular antiangiogenic therapy.

PMID- 22994141
TI  - 3D finite element models of shoulder muscles for computing lines of actions and
      moment arms.
AB  - Accurate representation of musculoskeletal geometry is needed to characterise the
      function of shoulder muscles. Previous models of shoulder muscles have
      represented muscle geometry as a collection of line segments, making it difficult
      to account for the large attachment areas, muscle-muscle interactions and complex
      muscle fibre trajectories typical of shoulder muscles. To better represent
      shoulder muscle geometry, we developed 3D finite element models of the deltoid
      and rotator cuff muscles and used the models to examine muscle function. Muscle
      fibre paths within the muscles were approximated, and moment arms were calculated
      for two motions: thoracohumeral abduction and internal/external rotation. We
      found that muscle fibre moment arms varied substantially across each muscle. For
      example, supraspinatus is considered a weak external rotator, but the 3D model of
      supraspinatus showed that the anterior fibres provide substantial internal
      rotation while the posterior fibres act as external rotators. Including the
      effects of large attachment regions and 3D mechanical interactions of muscle
      fibres constrains muscle motion, generates more realistic muscle paths and allows
      deeper analysis of shoulder muscle function. 

PMID- 22994142
TI  - Current practice and barriers to the management of sexual issues in rheumatology:
      results of a survey of health professionals.
AB  - OBJECTIVES: To explore multidisciplinary health professionals' (HPs) management
      of disease-related sexual issues in patients with rheumatic diseases, including
      their perceptions and assessments, and identify factors that prevent HPs from
      addressing sexuality as a topic with patients. METHODS: A self-constructed
      questionnaire was sent to 647 nurses, physicians, physiotherapists, occupational
      therapists, social workers, and psychologists working within rheumatology care. A
      multivariate logistic regression model of significant determinants for initiating
      sexual topics with patients was built. RESULTS: The mean age of the responders (n
      = 274, 42% response rate, 87% female) was 46 years. While 96% considered
      sexuality a relevant topic in rheumatology care, 71% seldom/never raised the
      topic. The patient was the main initiator (53%), and 88% of HPs gave the patient
      responsibility to initiate. The HPs with relevant education in sexuality were
      significantly more comfortable talking about sexuality (p < 0.001) and raised
      sexual issues significantly more often (p < 0.001). In the multivariate analyses,
      higher age [odds ratio (OR) 3.69], having relevant education (OR 3.16), and being
      comfortable to some extent (OR 3.62) or to a large extent (OR 5.58) remained
      significant predictors to initiating sexual topics. CONCLUSIONS: Although HPs
      regarded sexuality as a relevant topic in rheumatic health care, they seldom
      raised the topic in consultations. Those with further education in sexuality
      addressed sexual issues more frequently and felt more comfortable.
      Correspondingly, the majority of respondents requested more education. Such
      training should be part of the basic HPs' education, as well as part of
      postgraduate courses.

PMID- 22994143
TI  - Outcomes of steroid-avoidance protocols in pediatric kidney transplant
      recipients.
AB  - Advances in immunosuppression have facilitated increased use of steroid-avoidance
      protocols in pediatric kidney transplantation. To evaluate such steroid
      avoidance, a retrospective cohort analysis of pediatric kidney transplant
      recipients between 2002 and 2009 in the United Network for Organ Sharing database
      was performed. Outcomes (acute rejection and graft loss) in steroid-based and
      steroid-avoidance protocols were assessed in 4627 children who received
      tacrolimus and mycophenolate immunosuppression and did not have multiorgan
      transplants. Compared to steroid-based protocols, steroid avoidance was
      associated with decreased risk of acute rejection at 6 months posttransplant
      (8.3% vs. 10.9%, p = 0.02) and improved 5-year graft survival (84% vs. 78%, p <
      0.001). However, patients not receiving steroids experienced less delayed graft
      function (p = 0.01) and pretransplant dialysis, were less likely to be African
      American and more frequently received a first transplant from a living donor (all
      p < 0.001). In multivariate analysis, steroid avoidance trended toward decreased
      acute rejection at 6 months, but this no longer reached statistical significance,
      and there was no association of steroid avoidance with graft loss. We conclude
      that, in clinical practice, steroid avoidance appears safe with regard to graft
      rejection and loss in pediatric kidney transplant recipients at lower immunologic
      risk.

PMID- 22994144
TI  - Investigation of the physical-mechanical properties of Eudragit((r)) RS PO/RL PO
      and their mixtures with common pharmaceutical excipients.
AB  - Ammonio methacrylate copolymers Eudragit((r)) RS PO and Eudragit(r) RL PO have
      found widespread use as key components in various types of extended release solid
      dosage forms. The deformation behavior of neat polymers and binary mixes was
      evaluated using Heckel Analysis, strain rate sensitivity, work of compaction and
      elastic recovery index. Additionally, the compact forming ability of neat
      materials and binary mixes were evaluated by analyzing their tabletability,
      compressibility and compactibility profiles. The Heckel analysis of both polymers
      exhibited a speed-sensitive deformation behavior typical to plastic materials.
      The yield values of the binary mixes of the polymers with microcrystalline
      cellulose revealed a linear relationship with the weight fractions of individual
      components. The yield values of binary mixes of both the polymers with dibasic
      calcium phosphate exhibited slight negative deviations from linearity. Both
      polymers exhibited axial relaxation after ejection typical of viscoelastic
      materials, as measured by the elastic recovery index values. The work of
      compaction and the elastic recovery index values of the binary mixtures were
      found to be linearly related to the weight fractions of the individual components
      thus, confirming ideal mixing behavior based on the composition. Addition of
      microcrystalline cellulose to both polymers significantly improved their
      tabletability and compactibility. The tensile strengths of the compacts prepared
      with neat materials and binary mixes with microcrystalline cellulose, dibasic
      calcium phosphate and lactose were the function of their solid fraction and
      independent of the tableting speeds tested; thus, validating compactibility as a
      reliable parameter in predicting acceptable tablet properties.

PMID- 22994145
TI  - Analysis of isopropyl para-toluenesulphonate in palm-based esters by gas
      chromatography with flame ionization detection and confirmed with mass
      spectrometry.
AB  - A simple and rapid gas chromatography (GC) method with flame ionization detector
      was developed for detection of isopropyl para-toluenesulphonate (IPTS) in palm
      based isopropyl palmitate (IPP) and isopropyl myristate (IPM). The method
      involved spiking the IPP/IPM samples with IPTS and directly injecting the spiked
      samples into GC without undergoing clean-up steps. The calibration curves for
      IPTS showed good linearity with coefficient correlation of 0.9999 for six-point
      calibration from 0.5 to 50 MUg mL(-1)  and 0.9996 for six-point calibration from
      0.5 to 200 MUg mL(-1) . IPTS recoveries from IPP were 98.6-103.5% with relative
      standard deviation (RSD) of 0.40-2.80%, whereas recoveries from IPM were 97.0
      107.2% with RSD of 0.42-4.21%. The identity of IPTS recovered from the isopropyl
      esters was confirmed by a GC-mass spectrometer detector. The method was
      successfully applied to the analyses of IPTS in commercial samples. It was found
      that there were IPTS in the range of 34.8-1303.0 MUg g(-1)  in the palm-based
      esters for some of the samples analysed.

PMID- 22994146
TI  - Toward an understanding of the emotion-modulated startle eyeblink reflex: the
      case of anger.
AB  - Three studies investigated the effect of angering pictures on the startle
      eyeblink response, based on anger's unique identity as an approach-oriented
      negative affect. In Study 1, eyeblinks to startling noise probes during angering
      and neutral pictures did not differ, despite angering pictures being rated higher
      on arousal and anger and more negative in valence. Study 2 replicated Study 1;
      also, dysphoric participants exhibited potentiated eyeblinks to probes during
      angering pictures much like those to probes during fear/disgust stimuli. A follow
      up study revealed that dysphoric participants rated angering pictures higher in
      fear. Study 3 again found that eyeblinks to probes during angering and neutral
      pictures did not differ. Taken together, these results suggest that probes during
      angering stimuli elicit eyeblinks much like those during neutral stimuli, perhaps
      due to the competing influences of arousal, valence, and motivation on the
      startle eyeblink reflex.

PMID- 22994147
TI  - Magnetic resonance imaging features of sinonasal disorders in horses.
AB  - Diseases of paranasal sinuses and nasal passages in horses can be a diagnostic
      challenge because of the complex anatomy of the head and limitations of many
      diagnostic modalities. Our hypothesis was that magnetic resonance (MR) imaging
      would provide excellent anatomical detail and soft tissue resolution, and would
      be accurate in the diagnosis of diseases of the paranasal sinuses and nasal
      passages in horses. Fourteen horses were imaged. Inclusion criteria were lesions
      located to the sinuses or nasal passages that underwent MR imaging and subsequent
      surgical intervention and/or histopathologic examination. A low field, 0.3 tesla
      open magnet was used. Sequences in the standard protocol were fast spin echo T2
      sagittal and transverse, spin echo T1 transverse, short-tau inversion recovery
      (STIR) dorsal, gradient echo 3D T1 MPR dorsal (plain and contrast enhanced), spin
      echo T1 fatsat (contrast enhanced). Mean scan time to complete the examination
      was 53 min (range 39-99 min). Lesions identified were primary or secondary
      sinusitis (six horses), paranasal sinus cyst (four horses), progressive ethmoid
      hematoma (two horses), and neoplasia (two horses). The most useful sequences were
      fast spin echo T2 transverse and sagittal, STIR dorsal and FE3D MPR (survey and
      contrast enhanced). Fluid accumulation, mucosal thickening, presence of
      encapsulated contents, bone deformation, and thickening were common findings
      observed in MR imaging. In selected horses, magnetic resonance imaging is a
      useful tool in diagnosing lesions of the paranasal sinuses and nasal passages.

PMID- 22994148
TI  - Chemical characterization of automotive polyurethane foam using solid-phase
      microextraction and gas chromatography-mass spectrometry.
AB  - Solid-phase microextraction (SPME) coupled with gas chromatography-mass
      spectrometry (GC-MS) was used in this study to identify volatile organic
      compounds (VOCs) emitted from heated automotive polyurethane (PU) foam collected
      from 17 different automobiles located in Yuen Long, HK SAR. The samples (0.05 g
      each) underwent incubation inside 5-mL glass vials for 30 min, and the VOCs were
      then collected from the headspace with a polydimethylsiloxane fiber by insertion
      for 30 min. The VOCs were then qualitatively identified by GC-MS analysis and
      were mostly found to be saturated hydrocarbons. However, differences were noted
      from car to car in the retention time range of 10-23 min. The VOCs collected
      during this segment of retention time from the PU foams ranged from antioxidants,
      food preservatives, pesticides, plasticizers, flame retardants to antiseptic
      agents. The results obtained from this study therefore highlight the usefulness
      of SPME/GC-MS as a form of chemical characterization in the analysis of PU foams
      in forensic casework.

PMID- 22994149
TI  - EGFR overexpression in canine primary lung cancer: pathogenetic implications and
      impact on survival.
AB  - This study reports the main clinicopathological features of primary lung cancer
      (PLC) in 37 dogs, with special regard to the pathogenetic and prognostic role of
      epidermal growth factor receptor (EGFR) overexpression. For each case the
      following characteristics were evaluated: tumour-node-metastasis (TNM) stage,
      tumour histotype, histological grade, mitotic activity and immunohistochemical
      expression of EGFR. In samples with available normal lung tissue, the amount of
      background anthracosis was also measured by image analysis. In 27 tumours (73%) a
      variable number of cells (20-100%) stained positively for EGFR. The proportion of
      EGFR-positive tumours was significantly higher in cases with background
      anthracosis, and the amount of anthracosis was correlated with the percentage of
      positive tumour cells. Additionally, a trend towards shortened survival for the
      high EGFR group was observed. These findings suggest an involvement of EGFR
      signalling pathway in canine PLC, a negative prognostic significance of protein
      overexpression and its potential implication in air pollution carcinogenesis. 

PMID- 22994152
TI  - Homozygous deletions of CDKN2A are present in all dic(9;20)(p13.2;q11.2)-positive
      B-cell precursor acute lymphoblastic leukaemias and may be important for
      leukaemic transformation.

PMID- 22994150
TI  - Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the
      development of gastrointestinal diseases in Southeast Asian countries: a meta
      analysis.
AB  - BACKGROUND: Infection with cagA-positive, cagA EPIYA motif ABD type, and vacA s1,
      m1, and i1 genotype strains of Helicobacter pylori is associated with an
      exacerbated inflammatory response and increased risk of gastroduodenal diseases.
      However, it is unclear whether the prevalence and virulence factor genotypes
      found in Southeast Asia are similar to those in Western countries. Here, we
      examined the cagA status and prevalence of cagA EPIYA motifs and vacA genotypes
      among H. pylori strains found in Southeast Asia and examined their association
      with gastroduodenal disease. METHODS: To determine the cagA status, cagA EPIYA
      motifs, and vacA genotypes of H. pylori, we conducted meta-analyses of 13
      previous reports for 1,281 H. pylori strains detected from several Southeast
      Asian countries. RESULTS: The respective frequencies of cagA-positive and vacA
      s1, m1, and i1 genotypes among examined subjects were 93% (1,056/1,133), 98%
      (1,010/1,033), 58% (581/1,009), and 96% (248/259), respectively. Stratification
      showed significant variation in the frequencies of cagA status and vacA genotypes
      among countries and the individual races residing within each respective country.
      The frequency of the vacA m-region genotype in patients infected with East Asian
      type strains differed significantly between the northern and southern areas of
      Vietnam (p < 0.001). Infection with vacA m1 type or cagA-positive strains was
      associated with an increased risk of peptic ulcer disease (odds ratio: 1.46,
      95%CI: 1.01-2.12, p = 0.046 and 2.83, 1.50-5.34, p = 0.001, respectively) in the
      examined Southeast Asian populations. CONCLUSIONS: Both Western- and East Asian
      type strains of H. pylori are found in Southeast Asia and are predominantly cagA
      positive and vacA s1 type. In Southeast Asia, patients infected with vacA m1 type
      or cagA-positive strains have an increased risk of peptic ulcer disease. Thus,
      testing for this genotype and the presence of cagA may have clinical usefulness.

PMID- 22994153
TI  - A disproportionate role for mtDNA in Dobzhansky-Muller incompatibilities?
AB  - Evolution in allopatric populations can lead to incompatibilities that result in
      reduced hybrid fitness and ultimately reproductive isolation upon secondary
      contact. The Dobzhansky-Muller (DM) model nicely accounts for the evolution of
      such incompatibilities. Although DM incompatibilities were originally conceived
      as resulting of interactions between nuclear genes, recent studies have
      documented cases where incompatibilities have arisen between nuclear and
      mitochondrial genomes (mtDNA). Although mtDNA comprises only a tiny component
      (typically <<0.01%) of an organism's genetic material, several features of mtDNA
      may lead to a disproportionate contribution to the evolution of hybrid
      incompatibilities: (i) essentially all functions of mtDNA require interaction
      with nuclear gene products. All mtDNA-encoded proteins are components of the
      oxidative phosphorylation (OXPHOS) system and all mtDNA-encoded RNAs are part of
      the mitochondrial protein synthetic machinery; both processes require interaction
      with nuclear-encoded proteins for function. (ii) Transcription and replication of
      mtDNA also involve mitonuclear interactions as nuclear-encoded proteins must bind
      to regulatory motifs in the mtDNA to initiate these processes. (iii) Although
      features of mtDNA vary amongst taxa, metazoan mtDNA is typically characterized by
      high nucleotide substitution rates, lack of recombination and reduced effective
      population sizes that collectively lead to increased chance fixation of mildly
      deleterious mutations. Combined, these features create an evolutionary dynamic
      where rapid mtDNA evolution favours compensatory nuclear gene evolution,
      ultimately leading to co-adaptation of mitochondrial and nuclear genomes. When
      previously isolated lineages hybridize in nature or in the lab, intergenomic co
      adaptation is disrupted and hybrid breakdown is observed; the role of
      intergenomic co-adaptation in hybrid breakdown and speciation will generally be
      most pronounced when rates of mtDNA evolution are high or when restricted gene
      flow results in significant population differentiation.

PMID- 22994151
TI  - Loss to programme between HIV diagnosis and initiation of antiretroviral therapy
      in sub-Saharan Africa: systematic review and meta-analysis.
AB  - OBJECTIVES: To assess the proportion of patients lost to programme (died, lost to
      follow-up, transferred out) between HIV diagnosis and start of antiretroviral
      therapy (ART) in sub-Saharan Africa, and determine factors associated with loss
      to programme. METHODS: Systematic review and meta-analysis. We searched PubMed
      and EMBASE databases for studies in adults. Outcomes were the percentage of
      patients dying before starting ART, the percentage lost to follow-up, the
      percentage with a CD4 cell count, the distribution of first CD4 counts and the
      percentage of eligible patients starting ART. Data were combined using random
      effects meta-analysis. RESULTS: Twenty-nine studies from sub-Saharan Africa
      including 148,912 patients were analysed. Six studies covered the whole period
      from HIV diagnosis to ART start. Meta-analysis of these studies showed that of
      the 100 patients with a positive HIV test, 72 (95% CI 60-84) had a CD4 cell count
      measured, 40 (95% CI 26-55) were eligible for ART and 25 (95% CI 13-37) started
      ART. There was substantial heterogeneity between studies (P < 0.0001). Median CD4
      cell count at presentation ranged from 154 to 274 cells/MUl. Patients eligible
      for ART were less likely to become lost to programme (25%vs. 54%, P < 0.0001),
      but eligible patients were more likely to die (11%vs. 5%, P < 0.0001) than
      ineligible patients. Loss to programme was higher in men, in patients with low
      CD4 cell counts and low socio-economic status and in recent time periods.
      CONCLUSIONS: Monitoring and care in the pre-ART time period need improvement,
      with greater emphasis on patients not yet eligible for ART.

PMID- 22994154
TI  - Bioinformatic databases and resources in the public domain to aid HLA research.
AB  - Research in HLA as in any other field depends on information. Different groups
      have generated generic and specific resources and tools to support this research.
      The present review describes a qualified subset of these resources, which should
      cover the most important starting points for research in the HLA field. It
      discusses access to HLA allele sequences, allele frequencies, continues with
      general support to access to literature, DNA and protein sequence information,
      structural models, teaching books, databases with phenotypic datasets, alignment
      tools, peptide binding, statistical tools, guidelines and ambiguity coding.
      Following functionalities and databases have been included: IMGT/HLA, Immuno
      Polymorphism Database (IPD), allele frequencies*.net, a detailed look into NCBI
      (National Center of Biotechnology Information) with a subset of databases and
      tools, focusing on literature research, sequences, user-specific support tools
      and applications (PubMed, GenBank, MyNCBI, blast, Gene, MapViewer, Structure,
      CN3D, WorkBench, and dbMHC). This is followed by a brief survey of EBI
      EMBL/Ensemble, the sequence alignment tool Clustal, the peptide and ligand
      databases SYFPEITHI and Immune Epitope Database, and last but not least
      statistical packages and HLA allele coding resources PyPop, the Immuno-genomics
      Data Analysis Working Group and the NMDP informatics section. All databases and
      tools can be freely accessed. Data linked to individuals, however, might require
      authorization by a data access committee.

PMID- 22994155
TI  - HLA population genetics: a Lebanese population.
AB  - Human leukocyte antigen (HLA) typing was done in 426 Lebanese subjects of 88
      families, in which 347 haplotypes were identified. The A, B, C, DRB1, DRB3/4/5,
      DQB1 and DPB1 loci were typed at high resolution. This study shows that
      information theory, as originally developed by Claude Shannon in 1948, provides a
      promising theoretical foundation to study the population genetics of a genetic
      system like HLA. Although Lebanese carry HLA alleles found in other populations,
      the association of these alleles into haplotypes is quite unique. Comparisons are
      made with the main ethnic groups. Two haplotypes well represented in the Lebanese
      population are not identified in any global population: L1 = {A*26:01:01 -
      B*35:01:01:01- C*04:01:01:01- DRB1*16:01:01 - DRB5*02:02 - DQB1*05:02:01} and L2
      = {A*02:02 - B*41:01- C*17:01:01:01 -DRB1*11:04:01 - DRB3*02:02:01:01-
      DQB1*03:01:01:01}. By studying linkage disequilibrium in two blocks at a time,
      with the division of the blocks at different levels in consecutive cycles,
      conserved haplotypes in full linkage disequilibrium come to light, such as
      {A*26:01:01- B*35:01:01:01 - C*04:01:01:01 - DRB1*16:01:01 - DRB5*02:02 -
      DQB1*05:02:01- DPB1*03:01:01} and {A*33:01:01 - B*14:02:01 - C*08:02:01 -
      DRB1*01:02:01- DQB1*05:01:01:01 - DPB1*04:01:01:01}.

PMID- 22994156
TI  - Meta-analysis of randomized, controlled trials comparing particular doses of
      griseofulvin and terbinafine for the treatment of tinea capitis.
AB  - Two oral antifungal agents, griseofulvin and terbinafine, have regulatory
      approval in the United States, but it is unknown whether one has superior overall
      efficacy. Genus-specific differences in efficacy are believed to exist for the
      two agents. It is not clear at what doses and durations of treatment these
      differences apply. The goals of this meta-analysis were to determine whether a
      statistically significant difference in efficacy exists between these agents at a
      given dose and duration of each in tinea capitis infections overall and to
      determine whether a genus-specific difference in efficacy exists for these two
      treatments at a given dose and duration of each. We performed a literature search
      for clinically and methodologically similar randomized controlled trials
      comparing 8 weeks of griseofulvin (6.25-12.5 mg/kg/day) to 4 weeks of terbinafine
      (3.125-6.25 mg/kg/day) in the treatment of tinea capitis. A meta-analysis was
      performed using the Mantel-Haenszel method and random effects model; results were
      expressed as odds ratios with 95% confidence intervals. Meta-analysis of
      randomized controlled trials did not show a significant difference in the overall
      efficacy of the two drugs at the doses specified, but specific efficacy
      differences were observed based on the infectious species. For tinea capitis
      caused by Microsporum spp., griseofulvin is superior (p = 0.04), whereas
      terbinafine is superior for Trichophyton spp. infection (p = 0.04). Our results
      support species-specific differences in treatment efficacy between griseofulvin
      and terbinafine and provide a clinical context in which this knowledge may be
      applied.

PMID- 22994157
TI  - Genomic arrays in chronic lymphocytic leukemia routine clinical practice: are we
      ready to substitute conventional cytogenetics and fluorescence in situ
      hybridization techniques?
AB  - Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical
      course. Del(11q) and del(17p), routinely studied by conventional G-banding
      cytogenetics (CGC) and fluorescence in situ hybridization (FISH), have been
      related to progression and shorter overall survival. Recently, array-based
      karyotyping has gained acceptance as a high-resolution new tool for detecting
      genomic imbalances. The aim of the present study was to compare genomic arrays
      with CGC and FISH to ascertain whether the current techniques could be
      substituted in routine procedures. We analyzed 70 patients with CLL using the
      Cytogenetics Whole-Genome 2.7M Array and CytoScan HD Array (Affymetrix), CGC and
      FISH with the classical CLL panel. Whereas 31.4% and 68.6% of patients presented
      abnormalities when studied by CGC and FISH, respectively, these rates increased
      when arrays were also analyzed (78.6% and 80%). Although abnormality detection is
      higher when arrays are applied, one case with del(11q) and three with del(17p)
      were missed by genomic arrays due to their limited sensitivity. We consider that
      the complete substitution of CGC and FISH by genomic arrays in routine
      laboratories could negatively affect the management of some patients harboring
      11q or 17p deletions. In conclusion, genomic arrays are valid to detect known and
      novel genomic imbalances in CLL, but should be maintained as a complementary tool
      to the current techniques.

PMID- 22994158
TI  - LC-ESI-MS/MS analysis of testosterone at sub-picogram levels using a novel
      derivatization reagent.
AB  - Testosterone analysis by LC-MS/MS is becoming the analytical method of choice
      over immunoassays due to its specificity and accuracy. However, neutral steroid
      hormones possess poor ionization efficiency in MS/MS, resulting in insufficient
      sensitivity for analyzing samples with trace concentrations of the hormones. The
      method presented here utilizes a derivatization step involving a novel,
      permanently charged, quaternary aminooxy (QAO) reagent or MS-tag that reacts to
      the ketone functionality of testosterone and significantly enhances its ESI-MS/MS
      sensitivity. This derivatization method enabled quantitation of total
      testosterone in human serum (200 MUL) with a lower limit of quantitation (LLOQ)
      of 1 pg/mL (3.47 pmol/L), total testosterone in dried blood spots (8-10 MUL) with
      a LLOQ of 40 pg/mL, and free testosterone in serum ultrafiltrate (400 MUL) with a
      LLOQ of 0.5 pg/mL. The linearity of each of the high sensitivity applications was
      maintained over a broad dynamic range of 1-5000 pg/mL for the serum samples and
      40-10,000 pg/mL for the dried blood spots (DBS) with R(2) >0.998. The %CV at the
      LLOQ was <15 for all applications. The QAO derivatization and sample preparation
      workflows are quick, simple, and robust. Comparison of the derivatization method
      with an LC-ESI-MS/MS nonderivatization method yielded high correlation and
      agreement. The derivatization reagent is universal and reacts with other
      compounds containing ketone or aldehyde functionality.

PMID- 22994159
TI  - The scent of bacteria: headspace analysis for the discovery of natural products.
AB  - Volatile compounds released by 50 bacterial strains, 45 of them actinobacteria in
      addition to three chloroflexi and two myxobacteria, have been collected by use of
      a closed-loop stripping apparatus, and the obtained headspace extracts have been
      analyzed by GC-MS. Excluding terpenes that have recently been published
      elsewhere, 254 compounds from all kinds of compound classes have been identified.
      For unambiguous compound identification several reference compounds have been
      synthesized. Among the detected volatiles 12 new natural products have been
      found, in addition to mellein, which was released by Saccharopolyspora erythraea.
      The iterative PKS for this compound has recently been identified by in vitro
      experiments, but mellein production in S. erythraea has never been reported
      before. These examples demonstrate that headspace analysis is an important tool
      for the discovery of natural products that may be overlooked using conventional
      techniques. The method is also useful for feeding experiments with isotopically
      labeled precursors and was applied to investigate the biosynthesis of the unusual
      nitrogen compound 1-nitro-2-methylpropane, which arises from valine. Furthermore,
      several streptomycetes emitted compounds that were previously recognized as
      insect pheromones, thus questioning if bacterial symbionts are involved in insect
      communication.

PMID- 22994160
TI  - Syntheses, structures, and magnetic properties of a family of tetranuclear
      hydroxido-bridged Ni(II)2Ln(III)2 (Ln = La, Gd, Tb, and Dy) complexes: display of
      slow magnetic relaxation by the zinc(II)-dysprosium(III) analogue.
AB  - A new family of [2 * 2] tetranuclear 3d-4f heterometallic complexes have been
      synthesized. These are [Zn(2)Dy(2)L(2)(MU(3)-OH)(2)(MU(4)
      OH)(dbm)(2)(MeOH)(2)](NO(3)).2H(2)O.MeOH (3), [Ni(2)Dy(2)L(2)(MU(3)-OH)(2)(MU(4)
      OH)(dbm)(2)(MeOH)(2)](NO(3)).MeOH (4), [Ni(2)La(2)L(2)(MU(3)-OH)(2)(MU(4)
      OH)(dbm)(2)(MeOH)(2)](ClO(4)).H(2)O.2MeOH (5), [Ni(2)Tb(2)L(2)(MU(3)-OH)(2)(MU(4)
      OH)(dbm)(2) (MeOH)(2)](NO(3)).MeOH (6), and [Ni(2)Gd(2)L(2)(MU(3)-OH)(2)(MU(4)
      OH)(dbm)(2)(MeOH)(2)](NO(3)).MeOH (7), [H(2)L = N,N'-dimethyl-N,N'-bis(2-hydroxy
      3,5-dimethylbenzyl)ethylenediamine and Hdbm = dibenzoylmethane] obtained through
      a single-pot synthesis using [Zn(HL)(dbm)] (for 3)/[Ni(HL)(dbm)].2CH(3)OH (for 4,
      5, 6, and 7) as 3d-metal ion precursors. Single-crystal X-ray diffraction
      analysis and electrospray ionization (ESI) mass spectroscopy have been used to
      establish their identities. Compounds are isostructural, in which the metal ions
      are all connected together by a bridging hydroxido ligand in a rare MU(4)-mode.
      In complexes 3-7, the metal ions are antiferromagnetically coupled. Taking a cue
      from the results of 3 and 5, precise estimations have been made for the
      antiferromagnetic Ni...Ni (J(Ni) = -50 cm(-1)), Ni...Gd (J(NiGd) = -4.65 cm(-1)),
      and Gd...Gd (J(Gd) = -0.02 cm(-1)) exchange interactions in 7, involving the
      gadolinium(III) ions. The Zn(II)(2)Dy(III)(2) compound 3 has shown the tail of an
      out-of-phase signal in alternating current (AC) susceptibility measurement,
      indicative of slow relaxation of magnetization. Interestingly, the
      Ni(II)(2)Dy(III)(2) compound 4 in which both the participating metal ions possess
      large single ion anisotropy, has failed to show up any slow magnetic relaxation.

PMID- 22994161
TI  - Patterns of species richness among assemblages of Unionicola spp. (Acari:
      Unionicolidae) inhabiting freshwater mussels (Bivalvia: Unionoida) of North
      America.
AB  - Water mites of Unionicola species are common symbionts of freshwater mussels,
      living on the gills or mantle and foot of their hosts and using these tissues as
      sites of oviposition. Although surveys of the mite fauna among North American
      mussels suggest that these mites represent highly diverse assemblages, there are
      currently no quantitative data characterizing Unionicola species diversity among
      their molluscan hosts. The present study addresses patterns of species richness
      of Unionicola assemblages from freshwater mussels, including the relationship
      between richness and host specificity among these mites. Results from this study
      indicate that mite species richness increased significantly with an increase in
      the number of host individuals sampled. When corrected for sampling effort, there
      was a positive relationship between host size and mite species richness. Results
      from this study also reveal a significant relationship between mite species
      richness and the geographical distribution of host mussels. Overall, the patterns
      of species richness observed for this study are consistent with those examining
      the richness of parasitic helminth communities. Because the phylogenetic history
      of host taxa can have a significant influence on patterns of parasite species
      richness, studies that correct for the phylogenetic history among host mussels
      will be required to better understand the role that evolutionary processes have
      in determining Unionicola species richness. The present study did not indicate a
      significant relationship between species richness and host specificity and, in
      not doing so, suggests that the dispersal ability of mites may also play a role
      in influencing Unionicola species richness. The host recognition behavior and
      swimming abilities for a larger sample of mites will be required to substantiate
      this hypothesis.

PMID- 22994162
TI  - Design of an accuracy study for position detection in football.
AB  - Only a few studies have analysed the accuracy of position detection systems. All
      of them analysed distances and velocities, which are the outcome of calculations
      based on x,y positions. The objective of this study was to analyse the accuracy
      of dynamic x,y position measurement of a radar- and an image-based system in
      football. One and two runners performed five different runs on four different
      locations on a football pitch. X,y positions recorded by the radar-based and the
      image-based system were compared to x,y positions measured by a Laveg laser
      device. Accuracies were analysed by means of root mean square error (RMSE).
      Results showed that the radar-based system detects positions more accurately than
      the image-based system (P = 0.000). Mean RMSE of the radar-based system was 0.24
      m, RMSE of the image-based system was 0.73 m. The image-based system was
      significantly influenced by the location of the run, whereas the radar-based
      system was not. Based on the results of this study, we conclude that the radar
      based system is more valid in detecting x,y positions than the image-based
      system. Future studies should take advantage of the new test design which allows
      more precise statements on the accuracy of a position detection system.

PMID- 22994163
TI  - Novel taste-masked orally disintegrating tablets for a highly soluble drug with
      an extremely bitter taste: design rationale and evaluation.
AB  - The purpose of this study was to evaluate the taste masking potential of novel
      solid dispersions (SDs) using Eudragit(r) EPO as the excipient when incorporated
      into the orally disintegrating tablets (ODTs) for delivering a highly soluble
      drug with an extremely bitter taste. The pyridostigmine bromides (PB) SDs (PBSDs)
      were prepared by solvent evaporation-deposition method. The physicochemical
      properties of PBSDs were investigated by means of differential scanning
      calorimetry and Fourier transformed infrared spectroscopy. The dissolution test
      showed that only about 8% of PB was released from PBSDs in the simulated salivary
      fluid in 30 s. Therefore, PBSDs were considered taste-masked and selected for
      formulation of PBODTs. A central composite design was employed for process
      optimization. Multiple linear regression analysis for process optimization
      revealed that the optimal PBODTs were obtained, when the microcrystalline
      cellulose and crospovidone were 17.16 and 5.55 (%, w/w), respectively, and the
      average in vivo disintegration time was 25 s. The bitterness threshold of PB was
      examined by a sensory test, and the threshold value was set as 3 mg in each
      tablet. Taste evaluation of PBODTs in 18 volunteers revealed considerable taste
      masking with bitterness below the threshold value. PBODTs also revealed rapid
      drug release (around 99%, 2 min) in the simulated gastric fluid. The mean PB
      plasma concentration-time profiles of PBODTs and that of the commercial tablets
      were comparable, with closely similar pattern. Bioequivalence assessment results
      demonstrated that PBODTs and the commercial tablets were bioequivalent. In
      conclusion, PBODTs are prepared successfully, with taste masking and rapid
      disintegration in the oral cavity.

PMID- 22994164
TI  - Numerical analysis of dynamic temperature in response to different levels of
      reactive hyperaemia in a three-dimensional image-based hand model.
AB  - Vascular reactivity (VR) is considered as an effective index to predict the risk
      of cardiovascular events. A cost-effective alternative technique used to evaluate
      VR called digital thermal monitoring (DTM) is based on the response of finger
      temperature to vessel occlusion and reperfusion. In this work, a simulation has
      been developed to investigate hand temperature in response to vessel occlusion
      and perfusion. The simulation consists of image-based mesh generation and finite
      element analysis of blood flow and heat transfer in tissues. In order to
      reconstruct a real geometric model of human hand, a computer programme including
      automatic image processing for sequential MR data and mesh generation based on
      the transfinite interpolation method is developed. In the finite element analysis
      part, blood flow perfused in solid tissues is considered as fluid phase through
      porous media. Heat transfer in tissues is described by Pennes bioheat equation
      and blood perfusion rate is obtained from Darcy velocities. Capillary pressure,
      blood perfusion and temperature distribution of hand are obtained. The results
      reveal that fingertip temperature is strongly dependent on larger arterial
      pressure. This simulation is of potential to quantify the indices used for
      evaluating the VR in DTM test if it is integrated with the haemodynamic model of
      blood circulation in upper limb. 

PMID- 22994165
TI  - Accuracy and importance of projections from a dynamic simulation model of smoking
      prevalence in the United States.
AB  - We compared projections from a dynamic model of US adult smoking prevalence with
      official estimates of prevalence from the National Health Interview Survey. Ten
      years after they were made, the model projections closely fit the National Health
      Interview Survey estimates for 2005 and 2010. We conclude that a verified model
      of adult smoking prevalence can assist governmental authorities in establishing
      aspirational but feasible targets for tobacco control. By extension, carefully
      crafted models can help in goal setting in multiple areas of public health.

PMID- 22994166
TI  - Effectiveness of a risk screener in identifying hepatitis C virus in a primary
      care setting.
AB  - OBJECTIVES: We evaluated an intervention designed to identify patients at risk
      for hepatitis C virus (HCV) through a risk screener used by primary care
      providers. METHODS: A clinical reminder sticker prompted physicians at 3 urban
      clinics to screen patients for 12 risk factors and order HCV testing if any risks
      were present. Risk factor data were collected from the sticker; demographic and
      testing data were extracted from electronic medical records. We used the t test,
      chi(2) test, and rank-sum test to compare patients who had and had not been
      screened and developed an analytic model to identify the incremental value of
      each element of the screener. RESULTS: Among screened patients, 27.8% (n = 902)
      were identified as having at least 1 risk factor. Of screened patients with risk
      factors, 55.4% (n = 500) were tested for HCV. Our analysis showed that 7 elements
      (injection drug use, intranasal drug use, elevated alanine aminotransferase,
      transfusions before 1992, >= 20 lifetime sex partners, maternal HCV, existing
      liver disease) accounted for all HCV infections identified. CONCLUSIONS: A brief
      risk screener with a paper-based clinical reminder was effective in increasing
      HCV testing in a primary care setting.

PMID- 22994168
TI  - Measuring indoor air quality of hookah lounges.
AB  - Many states have implemented smoke-free workplace laws to protect employees and
      customers from exposure to secondhand smoke. However, exemptions in these laws
      have allowed indoor tobacco smoking in hookah lounges to proliferate in recent
      years. To describe the amount of secondhand smoke in hookah lounges, we measured
      the indoor air quality of 10 hookah lounges in Oregon. Air quality measurements
      ranged from "unhealthy" to "hazardous" according to Environmental Protection
      Agency standards, indicating a potential health risk for patrons and employees.

PMID- 22994167
TI  - Heterogeneity of falls among older adults: implications for public health
      prevention.
AB  - OBJECTIVES: We examined risk factors for falls among older people according to
      indoor and outdoor activity at the time of the fall and explored risk factors for
      seriously injurious falls. METHODS: Data came from MOBILIZE Boston, a prospective
      cohort study of 765 community-dwelling women and men, mainly aged 70 years or
      older. Over 4.3 years, 1737 falls were recorded, along with indoor or outdoor
      activity at the time of the fall. RESULTS: Participants with poor baseline health
      characteristics had elevated rates of indoor falls while transitioning, walking,
      or not moving. Healthy, active people had elevated rates of outdoor falls during
      walking and vigorous activity. For instance, participants with fast, rather than
      normal, gait speed, had a rate ratio of 7.36 (95% confidence interval [CI] =
      2.54, 21.28) for outdoor falls during vigorous activity. The likelihood of a
      seriously injurious fall also varied by personal characteristics, activity, and
      location. For example, the odds ratio for serious injury from an outdoor fall
      while walking outside compared to inside a participant's neighborhood was 3.31
      (95% CI = 1.33, 8.23). CONCLUSIONS: Fall prevention programs should be tailored
      to personal characteristics, activities, and locations.

PMID- 22994169
TI  - State cigarette excise tax, secondhand smoke exposure, and periodontitis in US
      nonsmokers.
AB  - OBJECTIVES: We assessed the relationship of state cigarette excise tax with
      cigarette sales, secondhand smoke (SHS) exposure, and periodontitis among US
      lifetime nonsmokers. METHODS: Cigarette excise tax and per capita sales data from
      1983 to 1998 were obtained for 50 states and the District of Columbia.
      Periodontal data were analyzed for 3137 adults in 28 states from 3 National
      Health and Nutrition Examination Survey cycles (1999-2004). Measures of
      periodontal pocket depth and attachment level were used to classify people with
      moderate or severe periodontitis. SHS exposure was classified according to gender
      or race/ethnicity-specific thresholds of serum cotinine concentration.
      Statistical analysis adjusted for the complex survey design. RESULTS: For each
      additional $0.10 in excise tax, predicted sales decreased by 0.74 packs per
      person per month and adjusted odds of moderate or severe periodontitis decreased
      22% (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.62, 0.97). For each
      pack sold per person per month, adjusted odds of SHS exposure increased 28% (95%
      CI = 1.17, 1.40) and adjusted odds of periodontitis increased 15% (95% CI = 1.03,
      1.29). Odds of periodontitis for those exposed to SHS were elevated 2-fold
      relative to those who were unexposed (OR = 2.03; 95% CI = 1.30, 3.20).
      CONCLUSIONS: Cigarette excise tax may protect nonsmokers against periodontitis.

PMID- 22994170
TI  - Self-help booklets for preventing postpartum smoking relapse: a randomized trial.
AB  - OBJECTIVES: We tested a series of self-help booklets designed to prevent
      postpartum smoking relapse. METHODS: We recruited 700 women in months 4 through 8
      of pregnancy, who quit smoking for their pregnancy. We randomized the women to
      receive either (1) 10 Forever Free for Baby and Me (FFB) relapse prevention
      booklets, mailed until 8 months postpartum, or (2) 2 existing smoking cessation
      materials, as a usual care control (UCC). Assessments were completed at baseline
      and at 1, 8, and 12 months postpartum. RESULTS: We received baseline
      questionnaires from 504 women meeting inclusion criteria. We found a main effect
      for treatment at 8 months, with FFB yielding higher abstinence rates (69.6%) than
      UCC (58.5%). Treatment effect was moderated by annual household income and age.
      Among lower income women (< $30 000), treatment effects were found at 8 and 12
      months postpartum, with respective abstinence rates of 72.2% and 72.1% for FFB
      and 53.6% and 50.5% for UCC. No effects were found for higher income women.
      CONCLUSIONS: Self-help booklets appeared to be efficacious and offered a low-cost
      modality for providing relapse-prevention assistance to low-income pregnant and
      postpartum women.

PMID- 22994171
TI  - High parenting aggravation among US immigrant families.
AB  - OBJECTIVES: We examined the association between the joint effects of children's
      immigrant family type and race/ethnicity on parenting aggravation. METHODS: We
      analyzed data on a nationally representative sample of 101 032 children aged
      birth through 17 years from the 2003 National Survey of Children's Health.
      RESULTS: Analysis of the Aggravation in Parenting Scale showed that 26% of
      foreign-born parents with foreign-born children were highly aggravated, followed
      by 22% of foreign-born parents with US-born children and 11% of US-born parents.
      Multivariable analyses indicated that all minority parents experienced high
      parenting aggravation compared with non-Hispanic White US-born parents; the odds
      of reporting parenting aggravation were 5 times higher for Hispanic foreign-born
      parents. All foreign-born parents, regardless of race/ethnicity, reported
      significantly elevated parenting aggravation. Parents of adolescents, children
      with special health care needs, and nontraditional and lower-income households
      were also more likely to report high parenting aggravation. CONCLUSIONS: Our
      findings clearly document significantly elevated levels of parenting aggravation
      among immigrant and minority families. Public health programs and clinicians
      should target referrals and interventions for these families to avoid potential
      health problems for both children and their families.

PMID- 22994172
TI  - A multidomain approach to understanding risk for underage drinking: converging
      evidence from 5 data sets.
AB  - OBJECTIVES: We examined the independent and combined influence of major risk and
      protective factors on youths' alcohol use. METHODS: Five large data sets provided
      similar measures of alcohol use and risk or protective factors. We carried out
      analyses within each data set, separately for boys and girls in 8th and 10th
      grades. We included interaction and curvilinear predictive terms in final models
      if results were robust across data sets. We combined results using meta-analytic
      techniques. RESULTS: Individual, family, and peer risk factors and a community
      protective factor moderately predicted youths' alcohol use. Family and school
      protective factors did not predict alcohol use when combined with other factors.
      Youths' antisocial attitudes were more strongly associated with alcohol use for
      those also reporting higher levels of peer or community risk. For certain risk
      factors, the association with alcohol use varied across different risk levels.
      CONCLUSIONS: Efforts toward reducing youths' alcohol use should be based on
      robust estimates of the relative influence of risk and protective factors across
      adolescent environment domains. Public health advocates should focus on context
      (e.g., community factors) as a strategy for curbing underage alcohol use.

PMID- 22994173
TI  - A ban on menthol cigarettes: impact on public opinion and smokers' intention to
      quit.
AB  - OBJECTIVES: We assessed support for a ban by the Food and Drug Administration on
      menthol in cigarettes and behavioral intentions among menthol smokers in the
      event of such a ban. METHODS: We surveyed 2649 never, former, and current smokers
      and used ordinal logistic regression to calculate weighted point estimates and
      predictors of support for a menthol ban among the adult population and menthol
      smokers only. For menthol smokers, we also calculated weighted point estimates
      and predictors of behavioral intentions. RESULTS: Overall, 28.2% of adults
      opposed, 20.0% supported, and 51.9% lacked a strong opinion about a menthol ban.
      Support was highest among Hispanics (36.4%), African Americans (29.0%), never
      smokers (26.8%), and respondents with less than a high school education (28.8%).
      Nearly 40% of menthol smokers said they would quit if menthol cigarettes were no
      longer available, 12.5% would switch to a nonmenthol brand, and 25.2% would both
      switch and try to quit. CONCLUSIONS: Support for a menthol ban is strongest among
      populations with the highest prevalence of menthol cigarette use. A menthol ban
      might motivate many menthol smokers to quit.

PMID- 22994174
TI  - Income inequality in health at all ages: a comparison of the United States and
      England.
AB  - OBJECTIVES: I systematically examined income gradients in health in the United
      States and England across the life span (ages birth to 80 years), separately for
      females and males, for a number of health conditions. METHODS: Using data from
      the National Health and Nutrition Examination Survey for the United States (n =
      36 360) and the Health Survey for England (n = 55 783), I calculated weighted
      prevalence rates and risk ratios by income level for the following health risk
      factors or conditions: obesity, hypertension, diabetes, low high-density
      lipoprotein cholesterol, high cholesterol ratio, heart attack or angina, stroke,
      and asthma. RESULTS: In the United States and England, the income gradients in
      health are very similar across age, gender, and numerous health conditions, and
      are robust to adjustments for race/ethnicity, health behaviors, body mass index,
      and health insurance. CONCLUSIONS: Health disparities by income are pervasive in
      England as well as in the United States, despite better overall health, universal
      health insurance, and more generous social protection spending in England.

PMID- 22994175
TI  - New Jersey's HIV exposure law and the HIV-related attitudes, beliefs, and sexual
      and seropositive status disclosure behaviors of persons living with HIV.
AB  - OBJECTIVES: We explored associations between awareness of New Jersey's HIV
      exposure law and the HIV-related attitudes, beliefs, and sexual and seropositive
      status disclosure behaviors of HIV-positive persons. METHODS: A statewide
      convenience sample (n = 479) completed anonymous written surveys during 2010. We
      recruited participants through networks of community-based organizations in the
      state's 9 health sectors. The survey assessed participants' awareness of New
      Jersey's HIV exposure law, their sexual and serostatus disclosure behavior in the
      past year, and their HIV-related attitudes and beliefs. We compared responses of
      participants who were and were not aware of the law through univariate analyses.
      RESULTS: Fifty-one percent of participants knew about the HIV exposure law. This
      awareness was not associated with increased sexual abstinence, condom use with
      most recent partner, or seropositive status disclosure. Contrary to hypotheses,
      persons who were unaware of the law experienced greater stigma and were less
      comfortable with positive serostatus disclosure. CONCLUSIONS: Criminializing
      nondisclosure of HIV serostatus does not reduce sexual risk behavior. Although
      the laws do not appear to increase stigma, they are also not likely to reduce HIV
      transmission.

PMID- 22994176
TI  - Ethical concerns in tobacco control nonsmoker and "nonnicotine" hiring policies:
      the implications of employment restrictions for tobacco control.
AB  - Smoking has been restricted in workplaces for some time. A number of
      organizations with health promotion or tobacco control goals have taken the
      further step of implementing employment restrictions. These restrictions apply to
      smokers and, in some cases, to anyone testing positive on cotinine tests, which
      also capture users of nicotine-replacement therapy and those exposed to
      secondhand smoke.  Such policies are defended as closely related to broader
      antismoking goals: first, only nonsmokers can be role models and advocates for
      tobacco control; second, nonsmoker and "nonnicotine" hiring policies help
      denormalize tobacco use, thus advancing a central aspect of tobacco control. 
      However, these arguments are problematic: not only can hiring restrictions come
      into conflict with broader antismoking goals, but they also raise significant
      problems of their own.

PMID- 22994177
TI  - Expected ethical competencies of public health professionals and graduate
      curricula in accredited schools of public health in North America.
AB  - OBJECTIVES: We assessed expected ethics competencies of public health
      professionals in codes and competencies, reviewed ethics instruction at schools
      of public health, and recommended ways to bridge the gap between them. METHODS:
      We reviewed the code of ethics and 3 sets of competencies, separating ethics
      related competencies into 3 domains: professional, research, and public health.
      We reviewed ethics course requirements in 2010-2011 on the Internet sites of 46
      graduate schools of public health and categorized courses as required, not
      required, or undetermined. RESULTS: Half of schools (n = 23) required an ethics
      course for graduation (master's or doctoral level), 21 did not, and 2 had no
      information. Sixteen of 23 required courses were 3-credit courses. Course content
      varied from 1 ethics topic to many topics addressing multiple ethics domains.
      CONCLUSIONS: Consistent ethics education and competency evaluation can be
      accomplished through a combination of a required course addressing the 3 domains,
      integration of ethics topics in other courses, and "booster" trainings. Enhancing
      ethics competence of public health professionals is important to address the
      ethical questions that arise in public health research, surveillance, practice,
      and policy.

PMID- 22994178
TI  - The United Nations High Level Meeting on the Prevention and Control of
      Noncommunicable Diseases: a missed opportunity?
AB  - The United Nations High Level Meeting on the Prevention and Control of
      Noncommunicable Diseases (September 19-20, 2011) provided an opportunity to
      recast the current global health agenda and offered a formidable platform to
      mobilize political will for concerted action.  We argue that the opportunity was
      missed because the World Health Organization (WHO) neglected the politics of
      process that are key to mobilizing political support for global noncommunicable
      disease policies. Instead, it focused on the implementation process.  The lessons
      to be drawn from the summit are critical because the WHO is the key agency that
      will be expected in the near future to steer further discussions and debate on
      the noncommunicable disease agenda.

PMID- 22994179
TI  - Prenatal, perinatal, early life, and sociodemographic factors underlying racial
      differences in the likelihood of high body mass index in early childhood.
AB  - OBJECTIVES: We investigated early childhood disparities in high body mass index
      (BMI) between Black and White US children. METHODS: We compared differences in
      Black and White children's prevalence of sociodemographic, prenatal, perinatal,
      and early life risk and protective factors; fit logistic regression models
      predicting high BMI (>= 95th percentile) at age 4 to 5 years to 2 nationally
      representative samples followed from birth; and performed separate and pooled
      survey estimations of these models. RESULTS: After adjustment for sample design
      related variables, models predicting high BMI in the 2 samples were statistically
      indistinguishable. In the pooled-survey models, Black children's odds of high BMI
      were 59% higher than White children's (odds ratio [OR] = 1.59; 95% confidence
      interval [CI]= 1.32, 1.92). Sociodemographic predictors reduced the racial
      disparity to 46% (OR = 1.46; 95% CI = 1.17, 1.81). Prenatal, perinatal, and early
      life predictors reduced the disparity to nonsignificance (OR = 1.18; 95% CI =
      0.93, 1.49). Maternal prepregnancy obesity and short-duration or no breastfeeding
      were among predictors for which racial differences in children's exposures most
      disadvantaged Black children. CONCLUSIONS: Racial disparities in early childhood
      high BMI were largely explained by potentially modifiable risk and protective
      factors.

PMID- 22994180
TI  - Deaths from secondhand smoke exposure in the United States: economic
      implications.
AB  - OBJECTIVES: We estimated the number of deaths attributable to secondhand smoke
      (SHS), years of potential life lost (YPLL), and value of lost productivity for
      different US racial/ethnic groups in 2006. METHODS: We determined the number of
      SHS-related deaths among nonsmokers from 2 adult and 4 infant conditions using an
      epidemiological approach. We estimated adult SHS exposure using detectable serum
      cotinine. For each death, we determined the YPLL and the value of lost
      productivity. Results. SHS exposure resulted in more than 42 000 deaths: more
      than 41 000 adults and nearly 900 infants. Blacks accounted for 13% of all deaths
      but 24% to 36% of infant deaths. SHS-attributable deaths resulted in a loss of
      nearly 600 000 YPLL and $6.6 billion of lost productivity, or $158 000 per death.
      The value of lost productivity per death was highest among Blacks ($238 000) and
      Hispanics ($193 000). CONCLUSIONS: The economic toll of SHS exposure is
      substantial, with communities of color having the greatest losses. Interventions
      need to be designed to reduce the health and economic burden of smoking on
      smokers and nonsmokers alike and on particularly vulnerable groups.

PMID- 22994181
TI  - Paul Meier: a man behind the method.

PMID- 22994182
TI  - The role of personal attributes in the genesis and progression of lung disease
      and cigarette smoking.
AB  - OBJECTIVES: We examined early maladaptive personal attributes (e.g., depression),
      later lung disease, and later maladaptive personal attributes over a significant
      part of a woman's life. METHODS: We gathered longitudinal data on a prospective
      cohort of community-dwelling women (n = 498) followed from young adulthood to
      late midlife. Results. We used structural equation modeling to assess the
      interrelations of maladaptive personal attributes, cigarette smoking, lung
      disease, and financial strain. The results supported a mediational model through
      which early maladaptive personal attributes were associated with smoking (b =
      0.17, P < .001), which in turn predicted later lung disease (b = 0.33, P < .001),
      and lung disease was related to later family financial difficulties (b = 0.09, P
      < .05), which in turn were associated with later maladaptive personal attributes
      (b = 0.35, P < .001). CONCLUSIONS: Our results address a number of important
      public health and clinical issues. An understanding of the interrelations of
      smoking, underlying mental health conditions, financial stress, and later mental
      health conditions on the part of physicians and other health care providers can
      be critical in managing patients with lung disease.

PMID- 22994183
TI  - Images of health. Training the mind's eye.

PMID- 22994184
TI  - Patients' rights and the National Health Service in Britain, 1960s-1980s.
AB  - The language of rights has long permeated discussions about health care in
      Britain, but during the latter half of the 20th century, patients' rights
      achieved a level of unprecedented prominence. By the end of the 1980s, the
      language of entitlement appeared to have spread into many areas of the National
      Health Service: consent to treatment, access to information, and the ability to
      complain were all legally established patients' rights. Patient organizations
      played a critical role in both realizing these rights and in popularizing the
      discourse of rights in health care in Britain. "Rights talk," however, was not
      without its drawbacks, as it was unclear what kinds of rights were being
      exercised and whether these were held by patients, consumers, or citizens.

PMID- 22994185
TI  - Up in smoke: vanishing evidence of tobacco disparities in the Institute of
      Medicine's report on sexual and gender minority health.
AB  - The Institute of Medicine (IOM) released a groundbreaking report on lesbian, gay,
      bisexual, and transgender (LGBT) health in 2011, finding limited evidence of
      tobacco disparities. We examined IOM search terms and used 2 systematic reviews
      to identify 71 articles on LGBT tobacco use. The IOM omitted standard tobacco
      related search terms. The report also omitted references to studies on LGBT
      tobacco use (n = 56), some with rigorous designs. The IOM report may
      underestimate LGBT tobacco use compared with general population use.

PMID- 22994186
TI  - A case study of the impact of inaccurate cause-of-death reporting on health
      disparity tracking: New York City premature cardiovascular mortality.
AB  - OBJECTIVES: Heart disease death overreporting is problematic in New York City
      (NYC) and other US jurisdictions. We examined whether overreporting affects the
      premature (< 65 years) heart disease death rate disparity between non-Hispanic
      Blacks and non-Hispanic Whites in NYC. METHODS: We identified overreporting
      hospitals and used counts of premature heart disease deaths at reference
      hospitals to estimate corrected counts. We then corrected citywide, age-adjusted
      premature heart disease death rates among Blacks and Whites and a White-Black
      premature heart disease death disparity. RESULTS: At overreporting hospitals, 51%
      of the decedents were White compared with 25% at reference hospitals. Correcting
      the heart disease death counts at overreporting hospitals decreased the age
      adjusted premature heart disease death rate 10.1% (from 41.5 to 37.3 per 100,000)
      among Whites compared with 4.2% (from 66.2 to 63.4 per 100,000) among Blacks.
      Correction increased the White-Black disparity 6.1% (from 24.6 to 26.1 per
      100,000). CONCLUSIONS: In 2008, NYC's White-Black premature heart disease death
      disparity was underestimated because of overreporting by hospitals serving larger
      proportions of Whites. Efforts to reduce overreporting may increase the observed
      disparity, potentially obscuring any programmatic or policy-driven advances.

PMID- 22994187
TI  - Type A behavior pattern and coronary heart disease: Philip Morris's "crown
      jewel".
AB  - The type A behavior pattern (TABP) was described in the 1950s by cardiologists
      Meyer Friedman and Ray Rosenman, who argued that TABP was an important risk
      factor for coronary heart disease. This theory was supported by positive findings
      from the Western Collaborative Group Study and the Framingham Study.  We analyzed
      tobacco industry documents to show that the tobacco industry was a major funder
      of TABP research, with selected results used to counter concerns regarding
      tobacco and health. Our findings also help explain inconsistencies in the
      findings of epidemiological studies of TABP, in particular the phenomenon of
      initially promising results followed by negative findings.  Our analysis suggests
      that these "decline effects" are partly explained by tobacco industry involvement
      in TABP research.

PMID- 22994188
TI  - Association between socioeconomic position discrimination and psychological
      distress: findings from a community-based sample of gay and bisexual men in New
      York City.
AB  - OBJECTIVES: We examined the association between discrimination and mental health
      distress, focusing specifically on the relative importance of discrimination
      because of particular demographic domains (i.e., race/ethnicity, socioeconomic
      position [SEP]). METHODS: The research team surveyed a sample of gay and bisexual
      men (n = 294) at a community event in New York City. Participants completed a
      survey on demographics, discrimination experiences in the past 12 months,
      attributed domains of discrimination, and mental health distress. RESULTS: In
      adjusted models, discrimination was associated with higher depressive (B = 0.31;
      P < .01) and anxious (B = 0.29; P < .01) symptoms. A statistically significant
      quadratic term (discrimination-squared; P < .01) fit both models, such that
      moderate levels of discrimination were most robustly associated with poorer
      mental health. Discrimination because of SEP was associated with higher
      discrimination scores and was predictive of higher depressive (B = 0.22; P < .01)
      and anxious (B = 0.50; P < .01) symptoms. No other statistically significant
      relationship was found between discrimination domains and distress. CONCLUSIONS:
      In this sample, SEP emerged as the most important domain of discrimination in its
      association with mental health distress. Future research should consider
      intersecting domains of discrimination to better understand social disparities in
      mental health.

PMID- 22994189
TI  - Mapping tobacco quitlines in North America: signaling pathways to improve
      treatment.
AB  - OBJECTIVES: This study was designed to better understand how the network of
      quitlines in the North American Quitline Consortium (NAQC) interact and share new
      knowledge on quitline practices. METHODS: Network relationship data were
      collected from all 63 publicly funded quitlines in North America, including
      information sharing, partner trust, and reputation. RESULTS: There was a strong
      tendency for US and Canadian quitlines to seek information from other quitlines
      in the same country, with few seeking information from quitlines from the other
      country. Quitlines with the highest reputation tended to more centrally located
      in the network, but the NAQC coordinating organization is highly central to the
      quitline network-thus demonstrating their role as a broker of quitline
      information. CONCLUSIONS: This first "snapshot" of US and Canadian quitlines
      demonstrated that smoking cessation quitlines in North America are not isolated,
      but are part of an interconnected network, with some organizations more central
      than others. As quitline use expands with the inclusion of national toll-free
      numbers on cigarette packs, how quitlines share information to improve practice
      will become increasingly important.

PMID- 22994190
TI  - A transnational study of migration and smoking behavior in the Mexican-origin
      population.
AB  - OBJECTIVES: We examined migration-related changes in smoking behavior in the
      transnational Mexican-origin population. METHODS: We combined epidemiological
      surveys from Mexico (Mexican National Comorbidity Survey) and the United States
      (Collaborative Psychiatric Epidemiology Surveys). We compared 4 groups with
      increasing US contact with respect to smoking initiation, persistence, and daily
      cigarette consumption: Mexicans with no migrant in their family, Mexicans with a
      migrant in their family or previous migration experience, migrants, and US-born
      Mexican Americans. RESULTS: Compared with Mexicans with a migrant in their family
      or previous migration experience, migrants were less likely to initiate smoking
      (odds ratio [OR] = 0.56; 95% confidence interval [CI] = 0.38, 0.83) and less
      likely to be persistent smokers (OR = 0.41; 95% CI = 0.26, 0.63). Among daily
      smokers, the US-born smoked more cigarettes per day than did Mexicans with a
      migrant in their family or previous migration experience for men (7.8 vs 6.5) and
      women (8.6 vs 4.3). CONCLUSIONS: Evidence suggests that smoking is suppressed
      among migrants relative to the broader transnational Mexican-origin population.
      The pattern of low daily cigarette consumption among US-born Mexican Americans,
      noted in previous research, represents an increase relative to smokers in Mexico.

PMID- 22994191
TI  - To flourish or not: positive mental health and all-cause mortality.
AB  - OBJECTIVES: We investigated whether positive mental health predicts all-cause
      mortality. METHODS: Data were from the Midlife in the United States (MIDUS) study
      (n = 3032), which at baseline in 1995 measured positive mental health
      (flourishing and not) and past-year mental illness (major depressive episode,
      panic attacks, and generalized anxiety disorders), and linked respondents with
      National Death Index records in a 10-year follow-up ending in 2005. Covariates
      were age, gender, race, education, any past-year mental illness, smoking,
      physical inactivity, physical diseases, and physical disease risk factors.
      RESULTS: A total of 6.3% of participants died during the study period. The final
      and fully adjusted odds ratio of mortality was 1.62 (95% confidence interval [CI]
      = 1.00, 2.62; P = .05) for adults who were not flourishing, relative to
      participants with flourishing mental health. Age, gender, race, education,
      smoking, physical inactivity, cardiovascular disease, and HIV/AIDS were
      significant predictors of death during the study period. CONCLUSIONS: The absence
      of positive mental health increased the probability of all-cause mortality for
      men and women at all ages after adjustment for known causes of death.

PMID- 22994192
TI  - Trends in US older adult disability: exploring age, period, and cohort effects.
AB  - OBJECTIVES: We elucidated how US late-life disability prevalence has changed over
      the past 3 decades. METHODS: We examined activities of daily living (ADL) and
      instrumental activities of daily living (IADL) disability trends by using age
      period-cohort (APC) models among older adults aged 70 years or older who
      responded to the National Health Interview Survey between 1982 and 2009. We
      fitted logistic regressions for ADL and IADL disabilities and for each of the 3
      APC trends with 2 models: unadjusted and fully adjusted for age, period, cohort,
      and sociodemographic variables. RESULTS: The unadjusted and adjusted period
      trends showed a substantial decline in IADL disability, and ADL disability
      remained stable across time. Unadjusted cohort trends for both outcomes also
      showed continual declines across successive cohorts; however, increasing cohort
      trends were evident in the adjusted models. CONCLUSIONS: More recent cohorts of
      US older adults are becoming more disabled, net of aging and period effects. The
      net upward cohort trends in ADL and IADL disabilities remain unexplained. Further
      studies should explore cohort-specific determinants contributing to the increase
      of cohort-based disability among US older adults.

PMID- 22994193
TI  - The decrease in the unintentional injury mortality disparity between American
      Indians/Alaska Natives and non-American Indians/Alaska Natives in New Mexico,
      1980 to 2009.
AB  - OBJECTIVES: We tracked the unintentional injury death disparity between American
      Indians/Alaska Natives and non-American Indians/Alaska Natives in New Mexico,
      1980 to 2009. METHODS: We calculated age-adjusted rates and rate ratios for
      unintentional injury deaths and their external causes among American
      Indians/Alaska Natives and non-American Indians/Alaska Natives. We tested trend
      significance with the Mann-Kendall test. RESULTS: The unintentional injury death
      rate ratio of American Indians/Alaska Natives to non-American Indians/Alaska
      Natives declined from 2.9 in 1980-1982 to 1.5 in 2007-2009. The rate among
      American Indians/Alaska Natives decreased 47.2% from 1980-1982 to 1995-1997.
      Among non-American Indians/Alaska Natives, the rate declined 25.3% from 1980-1982
      to 1992-1994, then increased 31.9% from 1992-1994 to 2007-2009. The motor vehicle
      traffic and pedestrian death rates decreased 57.8% and 74.6%, respectively, among
      American Indians/Alaska Natives from 1980-1982 to 2007-2009. CONCLUSIONS: The
      unintentional injury death rate disparity decreased substantially from 1980-1982
      to 2007-2009 largely because of the decrease in motor vehicle crash and
      pedestrian death rates among American Indians/Alaska Natives and the increase in
      the poisoning death rate among non-American Indians/Alaska Natives.

PMID- 22994194
TI  - HIV/AIDS surveillance data for New York City West Indian-born Blacks: comparisons
      with other immigrant and US-born groups.
AB  - OBJECTIVES: Although the risk of HIV among New York City West Indian-born Black
      immigrants often is assumed to be high, population-based data are lacking, a gap
      we aimed to address. METHODS: Using 2006-2007 HIV/AIDS surveillance data from the
      New York City Department of Health and Mental Hygiene and population data from
      the US Census American Community Survey 2007, we compared the rate of newly
      reported HIV diagnoses, prevalence of people living with HIV/AIDS, and
      distribution of transmission risk categories in West Indian-born Blacks, 2 other
      immigrant groups, and US-born Blacks and Whites. RESULTS: The age-adjusted rate
      of newly reported HIV diagnoses for West Indian-born Blacks was 43.19 per 100 000
      (95% confidence interval [CI] = 38.92, 49.10). This was higher than the rate
      among US-born Whites (19.96; 95% CI = 18.63, 21.37) and Dominican immigrants and
      lower than that among US-born Blacks (109.48; 95% CI = 105.02, 114.10) and
      Haitian immigrants. Heterosexual transmission was the largest risk category in
      West Indian-born Blacks, accounting for 41% of new diagnoses. CONCLUSIONS:
      Although much lower than in US-born Blacks, the rate of newly reported HIV
      diagnoses in West Indian-born Blacks exceeds that among US-born Whites.
      Additional work is needed to understand the migration-related sources of risk.

PMID- 22994195
TI  - Walking to school in Japan and childhood obesity prevention: new lessons from an
      old policy.
AB  - OBJECTIVES: We analyzed the Japan's walking-to-school practice implemented in
      1953 for lessons useful to other cities and countries. METHODS: We reviewed
      background documents (gray literature, online government information, local
      policy documents, and regulations) for existing regulations in several urban
      settings. We also contacted boards of education. RESULTS: Each municipality has a
      board of education in charge of public schools, which considers the geography,
      climate, and the transport situation to determine the method of commuting.
      Because there is high availability of schools in urban areas and most are located
      within walking range of the children's homes, walking is the most common method.
      There are different safety initiatives depending on the district's
      characteristics. Parents, school staff, and local volunteers are involved in
      supervision. CONCLUSIONS: The walk-to-school practice has helped combat childhood
      obesity by providing regular physical activity. Recommendations to cities
      promoting walking to school are (1) base interventions on the existing network of
      schools and adapt the provision to other local organizations, (2) establish
      safety measures, and (3) respond specifically to local characteristics. Besides
      the well-established safety interventions, the policy's success may also be
      associated with Japan's low crime rate.

PMID- 22994196
TI  - Incidence of disability among children 12 months after traumatic brain injury.
AB  - OBJECTIVES: We examined the burden of disability resulting from traumatic brain
      injuries (TBIs) among children younger than 18 years. METHODS: We derived our
      data from a cohort study of children residing in King County, Washington, who
      were treated in an emergency department for a TBI or for an arm injury during
      2007-2008. Disabilities 12 months after injury were assessed according to need
      for specialized educational and community-based services and scores on
      standardized measures of adaptive functioning and social-community participation.
      RESULTS: The incidence of children receiving new services at 12 months was about
      10-fold higher among those with a mild TBI than among those with a moderate or
      severe TBI. The population incidence of disability (defined according to scores
      below the norm means on the outcome measures included) was also consistently much
      larger (2.8-fold to 28-fold) for mild TBIs than for severe TBIs. CONCLUSIONS: The
      burden of disability caused by TBIs among children is primarily accounted for by
      mild injuries. Efforts to prevent these injuries as well as to decrease levels of
      disability following TBIs are warranted.

PMID- 22994197
TI  - Morbidity and mortality among newly hospitalized patients with community-acquired
      pneumococcal bacteremia: a retrospective cohort study in three teaching hospitals
      in Japan.
AB  - AIM: Although the mortality rate of pneumococcal bacteremia has been intensively
      studied, few studies have examined how it influences patient morbidity. This
      study aimed to fill this research gap by clarifying the impact of pneumococcal
      bacteremia on mortality and morbidity. METHODS: We carried out a retrospective
      cohort study of adult patients hospitalized with community-acquired pneumococcal
      bacteremia in three teaching hospitals in Japan from January 2003 to December
      2010. Morbidity was defined as a worsening Katz Index score compared with that
      before infection onset, new impairment of oral intake or new requirement for
      oxygen assistance at discharge. RESULTS: Of 135 patients identified (mean age 70
      years; 38% female), 116 (86%) were able to carry out activities of daily living
      independently before the onset of the infection. Pneumonia was found to be the
      most common infective source (69%), followed by meningitis (10%) and septic
      arthritis or vertebral osteomyelitis (8.1%). The 14-day, 30-day, and inpatient
      mortality rates were found to be 15%, 20% and 25%, respectively. The morbidity at
      discharge was 26 out of 101 (26%) among all survivors and 18 out of 42 (43%)
      among survivors who were aged >= 75 years. Multivariate analysis showed that an
      age of >= 75 years is an independent predictor of morbidity (adjusted odds ratio
      16.3, 95% CI 2.0-135.9). CONCLUSIONS: Our study showed that a high proportion of
      inpatient morbidity and mortality occurs in adult patients with pneumococcal
      bacteremia, especially among those aged >= 75 years.

PMID- 22994198
TI  - Phosphoribosyl pyrophosphate synthetase, as a suppressor of the sepH mutation in
      Aspergillus nidulans, is required for the proper timing of septation.
AB  - Timely cytokinesis/septation is essential for hyphal growth and conidiation in
      Aspergillus nidulans. Genetic analyses have identified that A. nidulans has
      components of the septum initiation network (SIN) pathway; one of these, SEPH, is
      a key player for early events during cytokinesis. However, little is known about
      how the SEPH kinase cascade is regulated by other components. Here, we
      demonstrate that the phosphoribosyl pyrophosphate synthetase family acts
      antagonistically against the SIN so that the downregulation of AnPRS family can
      bypass the requirements of the SIN for septum formation and conidiation. The
      transcription defect of the Anprs gene family accompanied with the reduction of
      AnPRS activity causes the formation of hyper-septation as well as the restoration
      of septation and conidiation in the absence of SEPH. Clearly, the timing and
      positioning of septation is related to AnPRS activity. Moreover, with the
      extensive yeast two-hybrid analysis and rescue combination experiments, it
      demonstrated that AnPRS members are able to form the heterodimers for functional
      interacting entities but they appear to contribute so unequally that Anprs1
      mutant display relatively normal septation, but Anprs2 deletion is lethal. Thus,
      compared to in yeast, the AnPRS family may have a unique regulation mechanism
      during septation in filamentous fungi.

PMID- 22994199
TI  - Nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents--a
      comprehensive review of biology, clinical course and treatment options.
AB  - Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is a unique variant of
      Hodgkin lymphoma with an overall good prognosis. It is conspicuously different
      from classical Hodgkin lymphoma (cHL) and is now recognized as distinctive form
      of B cell lymphoma. Although it has an indolent clinical course, it has a
      propensity for multiple and often late relapses. Although the majority of
      children present with early stage disease and without B symptoms, treatment
      strategy has, until recently, been identical to that used for cHL. This approach
      is excessively toxic as it predisposes these children and adolescents to serious
      late effects including end organ damage to heart, gonads, lungs, thyroid and
      second malignant neoplasms. The aim of this article is to review the published
      literature on the treatment outcomes of nLPHL in affected children and
      adolescents, and discuss the options for treatment including surgery,
      chemotherapy, radiotherapy and targeted anti-CD 20 antibody therapy.

PMID- 22994200
TI  - Associations of CD6, TNFRSF1A and IRF8 polymorphisms with risk of inflammatory
      demyelinating diseases.
AB  - AIMS: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory
      autoimmune diseases that affect the central nervous system. Several genome-wide
      and candidate gene studies have identified genetic polymorphisms associated with
      the risk of MS or NMO. In particular, two recently published studies of meta
      analysis in European-origin populations have suggested associations of single
      nucleotide polymorphisms (SNPs) in CD6, TNFRSF1A and IRF8 with MS. The aim of our
      study was to assess the associations between SNPs in these three genes and the
      risk of inflammatory demyelinating disease (IDD) including MS and NMO. To the
      best of our knowledge, this is the first time such a study has been performed in
      an Asian population. METHODS: A total of 21 SNPs of CD6, TNFRSF1A and IRF8 were
      genotyped in 178 IDD cases (79 MS and 99 NMO patients) and 237 normal controls in
      a Korean population. RESULTS: Logistic analyses revealed that one SNP in CD6
      (rs12288280, P = 0.04) and three SNPs in TNFRSF1A (rs767455, rs4149577 and
      rs1800693, P = 0.01-0.03) were associated with NMO. However, there was no
      association of IRF8 polymorphisms with IDD, including MS and NMO. Using further
      information from the SNP Function Prediction website, two exonic splicing
      enhancers (ESEs), including the polymorphic site of rs767455, were predicted to
      be binding sites for splicing factors (SRp55, SF2/ASF2 and SF2/ASF1). CONCLUSION:
      Although additional studies are needed, our findings could provide information
      regarding the genetic aetiology of IDD in the Korean population.

PMID- 22994201
TI  - A review on the extensive skin benefits of mineral oil.
AB  - This review was initially prepared in 2011 before Professor Johann Wiechers
      tragically passed away. It has been updated and is being published in his memory.
      It discusses the importance of mineral oil and its benefits to skin. Its source,
      structure, properties and efficacy are discussed. Mineral oil has been shown to
      improve skin softness and barrier function better than some other emollients
      using the gas-bearing dynamometer and standard water vapour transmission testing
      as well as in vivo studies showing its effects on suppressing transepidermal
      water loss (TEWL). It has also been subjected to the rigour of the newer in vivo
      confocal microscopic measurements now used for testing the performance of
      moisturizers by following the swelling characteristics of the stratum corneum and
      been found favourable compared with many vegetable oils. Its introduction as a
      cosmetic oil was in the late 1800s, and still today, it is used as one of the
      main components of moisturizers, a true testament to its cost to efficacy window.
      Naturally, it has physical effects on the stratum corneum, but it is expected
      that these will translate into biological effects simply through its mechanism of
      hydrating and occluding the stratum corneum from which many benefits are derived.

PMID- 22994202
TI  - Visual impairment caused by periorbital edema in an infant with acute hemorrhagic
      edema of infancy.
AB  - Acute hemorrhagic edema of infancy (AHEI) is a cutaneous vasculitis seen in
      children. Many consider it to be a clinical variant of Schonlein-Henoch purpura,
      but others regard it as a separate entity because of its benign nature, age of
      onset, lack of visceral involvement, and frequent absence of vascular
      immunoglobulin A deposition. It is clinically characterized by large "cockade" or
      rosette-shaped, annular, purpuric lesions involving the face and extremities;
      erythematous edema; and mild fever. It seems to appear secondary to a history of
      viral or bacterial infection, course of antibiotics, or vaccination. Because of
      the unknown etiology and benign character, which leads to spontaneous complete
      recovery, there is no specific treatment necessary for AHEI, and according to the
      literature, systemic corticosteroids do not seem to alter the course of the
      disease. We report the case of an 11-month-old boy who manifested massive
      periorbital edema along with all of the clinical characteristics of this entity
      and showed clear improvement of the symptoms after a 24-hour administration of
      systemic corticosteroid therapy. Given the positive effect of this therapy, we
      propose that systemic corticosteroids should be used to ameliorate the acute
      manifestations and avoid the rapid progression of the disease. 

PMID- 22994203
TI  - MBL2 gene variation affecting serum MBL is associated with prosthetic joint
      infection in Czech patients after total joint arthroplasty.
AB  - Prosthetic joint infection (PJI) is a serious complication of the total joint
      arthroplasty (TJA). Serum mannose-binding lectin (MBL), a pattern recognition
      receptor, is involved in antibacterial immune response. This study investigated
      whether functional variants of the MBL2 gene may be associated with the risk of
      PJI. MBL2 -550 (H/L, rs11003125), MBL2 -221 (Y/X, rs7096206) and MBL2 +54 (G/A,
      rs1800450) single nucleotide polymorphisms (SNP) were genotyped in 112 PJI
      patients and two control groups: 245 patients with aseptic TJA and 196 Czech
      population controls without TJA. Serum MBL concentration was assessed in PJI
      patients (n = 92) and aseptic TJA controls (n = 56). The distribution of MBL2
      genotypes complied with the Hardy-Weinberg equilibrium in all investigated
      groups. Importantly, MBL2 -550 L allele (allelic frequency, 0.72) and LL genotype
      (genotype frequency, 0.51) were more frequent among PJI patients compared to
      aseptic TJA controls (L allele: 0.63, P = 0.016, P(c) = 0.048; LL genotype: 0.39,
      P = 0.037, P(c) > 0.05) and to Czech population controls (L allele: 0.61, P =
      0.010, P(c) = 0.030; LL genotype: 0.35, P = 0.006, P(c) = 0.018), respectively.
      Regarding MBL protein, the MBL2 -550 L carriers presented with lower serum MBL
      concentrations than non-carriers (median; 593 vs 1876 ng/ml; P < 0.01).
      Similarly, the carriage of MBL2 -221 X and 54 A alleles was associated with lower
      serum MBL concentrations (P < 0.01). In conclusion, MBL2 -550 genetic variant(s)
      associated with low serum concentration of MBL protein can increase the risk of
      PJI.

PMID- 22994204
TI  - Closure of the abdominal wall with acellular dermal allograft in intestinal
      transplantation.
AB  - Loss of abdominal domain is a common problem in intestinal transplantation.
      Several surgical options are available perioperatively for abdominal wall
      reconstruction. This study reports the management and complications for
      intestinal transplant patients with abdominal wall closure either primarily or
      with foreign material. This single center study reviews the records of intestinal
      transplant patients between 2004 and 2010. Study outcomes included reoperation
      for dehiscence, hernia or enterocutaneous fistula. There were 37 of 146 patients
      (25%) who required implantation of foreign material at transplant. Of these 37,
      30 (81%) had implantation of acellular dermal allograft (ADA) and 7 (19%)
      implantation of another mesh. Perioperative dehiscence was rare with 2/109 (2%)
      for primary closure, 0/30 (0%) for ADA and 1/7 (14%) for other mesh. There were
      12/146 (8%) patients who underwent ventral hernia repair: primary closure 7/109
      (6%), ADA 3/30 (10%) and other mesh 2/7 (28%). There were 4/146 (3%) patients who
      required surgery for enterocutaneous fistulas: 2/109 (2%) primary closure, 1/30
      (3%) ADA and 1/7 (14%) synthetic mesh. Abdominal wall reconstruction with ADA
      biologic mesh provides an expeditious means of performing a tension-free closure
      of the fascial layer after intestinal transplantation with complications similar
      to those seen for primary closure.

PMID- 22994205
TI  - Diagnosis of treponemal co-infection in HIV-infected West Africans.
AB  - OBJECTIVES: To evaluate the performance of two enzyme immunoassays (EIA), Murex
      and ICE, and the Determine TP point-of-care test (POCT) in diagnosing treponemal
      infection (syphilis or yaws) in patients attending a large HIV clinic in Ghana;
      to determine the prevalence of treponemal co-infections; and to characterise
      demographic and clinical features of patients with infection. METHODS: Samples
      were tested with EIAs and rapid plasma reagin (RPR), then POCT and reference
      assays for Treponema pallidum to determine prevalence of active and past
      infection. Sensitivity and specificity of each assay were calculated and
      demographic and clinical characteristics of patients compared. Data were
      collected from case notes of patients retrospectively. RESULTS: Overall, 45/284
      patient samples (14.8%, 95% CI, 11.1-19.4%) were Treponema pallidum particle
      agglutination (TPPA) positive, and of these, 27 (64.3%) were RPR positive and 4
      (8.9%) were treponemal IgM positive. Both EIAs and Determine TP POCT showed high
      sensitivities and specificities for identifying infection although RPR was less
      reliable. Clinical features of syphilis or yaws were rarely identified in TPPA
      positive patients suggesting most had previous or late latent infection.
      Treatment of various intercurrent infections using short courses of antibiotics
      active against T. pallidum was common in the clinic. CONCLUSIONS: A high
      proportion of this HIV-infected cohort showed evidence of treponemal infection.
      Both EIAs as well as the POCT were practical and effective at diagnosing
      treponemal co-infection in this setting. RPR alone was unreliable at identifying
      active treponemal co-infection, however might be useful in some settings where
      treponemal-specific assays are unaffordable.

PMID- 22994207
TI  - The identification of spiromesifen, a recently introduced pesticide, using
      approaches to chemical unknown analysis.
AB  - An unknown, viscous, opaque, white liquid with a strong, unpleasant odor was
      submitted with a request for identification. It was analyzed using infrared (IR)
      spectroscopy, gas chromatography-mass spectrometry, and X-ray fluorescence
      spectroscopy. It was found to contain glycerin as well as another compound. IR
      and mass spectral data were readily obtained for this second component, but it
      was not easily identified as common instrument libraries had no matching spectra.
      After an extensive literature search, the unknown compound was identified as
      spiromesifen, a recently introduced pesticide. The IR spectrum and electron
      impact mass spectrum of spiromesifen are presented here as these are not
      available in the published literature. This case report also provides useful
      approaches for searching for and identifying an unknown compound when it is not
      found in a laboratory's spectral libraries.

PMID- 22994206
TI  - Vertebral heart scores in eight dog breeds.
AB  - The vertebral heart score (VHS) measurement is commonly used to provide a more
      objective measurement of cardiomegaly in canines. However, several studies have
      shown significant breed variations from the value previously established by
      Buchanan and Bucheler (9.7 +/- 0.5). This study describes VHS measurements in
      Pug, Pomeranian, Yorkshire Terrier, Dachshund, Bulldog, Shih Tzu, Lhasa Apso, and
      Boston Terrier dog breeds. Dogs with two or three view thoracic radiographs, no
      subjective radiographic evidence of cardiomegaly, and no physical examination
      findings of heart murmurs or gallop rhythms were included in the study. The Pug,
      Pomeranian, Bulldog, and Boston Terrier groups were found to have a VHS
      significantly greater than 9.7 +/- 0.5 (P < 0.00001, P = 0.0014, P < 0.0001, P <
      0.00001, respectively). Body condition score (BCS) was found to have a
      significant effect on the VHS of Lhasa Apso group. Anomalous vertebrae in the
      thoracic column were associated with a significant increase in VHS of the Bulldog
      (P = 0.028) and Boston Terrier (P = 0.0004) groups. Thoracic depth to width ratio
      did not have a significant effect on VHS.

PMID- 22994208
TI  - Neuropathic pain intensity, unpleasantness, coping strategies, and psychosocial
      factors after spinal cord injury: an exploratory longitudinal study during the
      first year.
AB  - OBJECTIVE: To determine the temporal relationship between pain-related coping
      strategies and psychosocial factors with non-evoked neuropathic pain (NP)
      intensity and unpleasantness in patients during the subacute phase of spinal cord
      injury (SCI). DESIGN: Exploratory longitudinal study of NP from 2 to 12 months.
      SETTING: Hospital Nacional de Paraplejicos, Toledo, Spain. SUBJECTS: A maximum of
      26 patients with early symptoms of NP after SCI with a neurological level above
      the Th10 spinal level. OUTCOME MEASURES:  Multidimensional Pain Inventory-Spinal
      Cord Injury Version, Coping Strategies Questionnaire, General 7-day pain
      intensity and unpleasantness rated with a visual analog scale, Spearman
      correlation analysis. RESULTS: PAIN-related coping strategies and psychosocial
      factors remained stable from 2 to 12 months after SCI. Initially pain intensity
      and unpleasantness were rated independently, but at 6 months were intercorrelated
      along with "pain severity,""life interference," and "catastrophizing.""Coping
      self-statements" and "solicitous responses from others" were frequently adopted,
      compared with "ignoring pain sensations" and "catastrophising." Perception of
      "pain severity" correlated with "support,""solicitous responses from
      others,""distracting responses from others," and "life control" at 6 months,
      while pain intensity and unpleasantness were related to "coping self
      statements,""catastrophizing,""distancing from pain," and "praying." CONCLUSIONS:
      Pilot longitudinal data suggest that pain-related coping strategies are adopted
      early after subacute SCI, and correlate with both pain intensity and
      unpleasantness. Future longitudinal studies of SCI with sufficient sample size
      will be instrumental to determine the causal relationship between psychosocial
      factors and coping strategies on pain.

PMID- 22994209
TI  - Contiguous ABCD1 DXS1357E deletion syndrome: report of an autopsy case.
AB  - Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion
      syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is
      responsible for X-linked adrenoleukodystrophy (X-ALD), its phenotype differs from
      that of CADDS, which manifests with many features of Zellweger syndrome (ZS),
      including severe growth and developmental retardation, liver dysfunction,
      cholestasis and early infantile death. We report here the fourth case of CADDS,
      in which a boy had dysmorphic features, including a flat orbital edge,
      hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and
      club feet, all of which are shared by ZS. The patient achieved no developmental
      milestones and died of pneumonia at 8 months. Biochemical studies demonstrated
      abnormal metabolism of very long chain fatty acids, which was higher than that
      seen in X-ALD. Immunocytochemistry and Western blot showed the absence of ALD
      protein (ALDP) despite the presence of other peroxisomal proteins. Pathological
      studies disclosed a small brain with hypomyelination and secondary hypoxic
      ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal
      glioneuronal heterotopia indicated a neuronal migration disorder. The liver
      showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic.
      Array comparative genomic hybridization (CGH) analysis suggested that the
      deletion was a genomic rearrangement in the 90-kb span starting in
      DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending
      in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B
      cell antigen receptor associated protein 31 (BAP31) and other factors, severely
      affects VLCFA metabolism on peroxisomal functions and produces ZS-like pathology.

PMID- 22994210
TI  - Fine-scale spatiotemporal patterns of genetic variation reflect budding dispersal
      coupled with strong natal philopatry in a cooperatively breeding mammal.
AB  - The relatedness structure of animal populations is thought to be a critically
      important factor underlying the evolution of mating systems and social
      behaviours. While previous work has shown that population structure is shaped by
      many biological processes, few studies have investigated how these factors vary
      over time. Consequently, we explored the fine-scale spatiotemporal genetic
      structure of an intensively studied population of cooperatively breeding banded
      mongooses (Mungos mungo) over a 10-year period. Overall population structure was
      strong (average F(ST)  = 0.129) but groups with spatially overlapping territories
      were not more genetically similar to one another than noncontiguous groups.
      Instead, genetic differentiation was associated with historical group-fission
      (budding) events, with new groups diverging from their parent groups over time.
      Within groups, relatedness was high within but not between the sexes, although
      the latter increased over time since group formation due to group founders being
      replaced by philopatric young. This trend was not mirrored by a decrease in
      average offspring heterozygosity over time, suggesting that close inbreeding may
      often be avoided, even when immigration into established groups is virtually
      absent and opportunities for extra-group matings are rare. Fine-scale
      spatiotemporal population structure could have important implications in social
      species, where relatedness between interacting individuals is a vital component
      in the evolution of patterns of inbreeding avoidance, reproductive skew and kin
      selected helping and harming.

PMID- 22994211
TI  - The objectivity of reporters: interference between physically unlinked promoters
      affects reporter gene expression in transient transfection experiments.
AB  - Despite inherent limitations, the ease and rapidity of their use make transiently
      expressed reporter gene assays the most frequently used techniques for analyzing
      promoters and transcriptional regulators. The results of transient reporter gene
      assays are generally accepted to reflect transcriptional processes correctly,
      though these assays study regulatory sequences outside of the chromosomal
      environment and draw conclusions on transcription based on enzyme activity
      determination. For transient reporter gene assays, often more than one promoter
      is introduced into one cell. In addition to the one driving the primary reporter
      gene expression, a further one might serve to ensure the production of an
      internal control second reporter or/and a trans-acting factor. We demonstrate
      here by various examples that interference between physically unlinked promoters
      can profoundly affect reporter expression. Results of reporter gene assays
      performed by combinations of the cytomegalovirus promoter and various other
      promoter constructs (human immunodeficiency virus [HIV], Human T-cell Leukemia
      Virus Type I (HTLV-I), NF-kappaB-responsive, and p53-responsive) and trans
      activator factors (HIV-Tat and p53) in different host cell lines (U2OS, HeLa, and
      L929) prove that interference between active transcription units can modify
      transcription responses dramatically. Since the interference depends on the
      promoters used, on the amount of transfected DNA, on the host cells, and on other
      factors, extra caution is required in interpreting results of transient reporter
      gene assays.

PMID- 22994212
TI  - A highly sensitive and specific genetic marker to diagnose aspirin-exacerbated
      respiratory disease using a genome-wide association study.
AB  - The aim of the present study was to develop a diagnostic set of single-nucleotide
      polymorphisms (SNPs) for discriminating aspirin-exacerbated respiratory disease
      (AERD) from aspirin-tolerant asthma (ATA) using the genome-wide association study
      (GWAS) data; the GWAS data were filtered according to p-values and odds ratios
      (ORs) using PLINK software, and the 10 candidate SNPs most closely associated
      with AERD were selected, based on 100 AERD and 100 ATA subjects. Using multiple
      logistic regression and receiver-operating characteristic (ROC) curve analysis,
      eight SNPs were chosen as the best model for distinguishing between AERD and ATA.
      The relative risk for AERD in each subject was calculated based on the relative
      risk of each of the eight SNPs. Ten of the original 109,365 SNPs highly
      associated (filtered with p<0.001 and ORs) with the risk for AERD were selected.
      A combination model of the eight SNPs among the 10 SNPs showed the highest area
      under the ROC curve of 0.9. The overall relative risk for AERD based on the eight
      SNPs was significantly different between the AERD and ATA groups (p=2.802E-21),
      and the sensitivity and specificity were 78% and 88%, respectively. The candidate
      set of eight SNPs may be useful in predicting the risk for AERD.

PMID- 22994213
TI  - DNA damage in lens epithelium of cataract patients in vivo and ex vivo.
AB  - PURPOSE: DNA damage has been described in the human cataractous lens epithelium,
      and oxidative stress generated by UV radiation and endogenous metabolic processes
      has been suggested to play a significant role in the pathogenesis of cataract. In
      this study, the aim was to explore the quality and relative quantity of DNA
      damage in lens epithelium of cataract patients in vivo and after incubation in a
      cell culture system. METHODS: Capsulotomy specimens were analysed, before and
      after 1 week of ex vivo cultivation, using the comet assay to measure DNA strand
      breaks, oxidized purine and pyrimidine bases and UV-induced cyclobutane
      pyrimidine dimers. RESULTS: DNA strand breaks were barely detectable, oxidized
      pyrimidines and pyrimidine dimers were present at low levels, whereas there was a
      relatively high level of oxidized purines, which further increased after
      cultivation. CONCLUSION: The observed levels of oxidized purines in cataractous
      lens epithelium may support a theory consistent with light damage and oxidative
      stress as mediators of molecular damage to the human lens epithelium. Damage
      commonly associated with UV-B irradiation was relatively low. The levels of
      oxidized purines increased further in a commonly used culture system. This is of
      interest considering the importance and versatility of ex vivo systems in studies
      exploring the pathogenesis of cataract.

PMID- 22994214
TI  - Advanced multimodal CT/MRI approaches to hyperacute stroke diagnosis, treatment,
      and monitoring.
AB  - Multimodal CT/MRI has dramatically changed the approach to ischemic stroke
      management, as noninvasive CT/MRI images detail brain tissue or parenchyma,
      angiography or vessel status, and collateral perfusion or blood flow in regions
      of the brain vulnerable to ischemic injury. Such snapshots of the dynamic process
      of cerebral ischemia may be used to gauge reversibility and therapeutic
      opportunities. Treatment of acute stroke may be rapidly tailored to clinical
      scenarios based on imaging correlation of ischemia, vessel status, and perfusion.
      Serial or repeated imaging from the initial presentation to later stages of the
      hospital course may illustrate infarct growth, persisting occlusion, reocclusion,
      recanalization, reperfusion, and hemorrhagic transformation. From acute stroke to
      rehabilitation phases and subsequent prevention, multimodal CT/MRI has emerged as
      a key tool to track the process of stroke and the impact of our therapeutic
      interventions.

PMID- 22994215
TI  - The future of stroke thrombolysis.
AB  - Studies with tissue plasminogen activator (t-PA) published in 1995 showed
      significant improvement in stroke outcome if the drug was administered within 3
      hours from stroke onset. Several recent reports, however, show that less than 5%
      of stroke patients may be receiving t-PA in many parts of North America. This
      paper explores how this may be improved by examining some of the steps taken in
      Canada, where a recent audit showed that 8.2% of ischemic stroke patients
      received t-PA, and in those arriving within 2.5 hours to regional stroke centers
      in Ontario, 42.2% received t-PA. The paper also reviews the potential for t-PA to
      be given by more physicians, in remote regions using Telestroke, the possibility
      for using imaging characteristics rather than the onset of stroke as a
      determinant of eligibility for t-PA, the status of contraindications for
      thrombolysis, and the possibility of combining t-PA with immune modulation for
      improved stroke outcomes.

PMID- 22994216
TI  - Population shifts and the future of stroke: forecasts of the future burden of
      stroke.
AB  - Population distribution estimates by age and race/ethnicity from the U.S. Census
      Bureau for the years 2010 and 2050 were combined with estimates of stroke
      incidence from population-based surveillance studies to forecast the distribution
      of incident stroke cases for the years 2010 and 2050. Over these 40 years, the
      number of incident strokes will more than double, with the majority of the
      increase among the elderly (age 75+) and minority groups (particularly
      Hispanics). These increases are likely to present major logistical, scientific,
      and ethnical issues in the near future.

PMID- 22994217
TI  - Pathobiology of injury after stroke: the neurovascular unit and beyond.
AB  - Throughout the history of research on stroke pathophysiology, focus has shifted
      from purely vascular concepts to the insight that a complex interplay of
      biochemical and molecular mechanisms involving practically any cell type of the
      brain ("neurovascular unit") partakes in either salvage or demise of the tissue
      after a stroke. In addition, it was realized that peripheral immune cells play
      important roles, not only after their invasion into the brain but also because of
      stroke-induced effects on the immune system that can result in infections.
      Indeed, outcome of stroke patients is not only dictated by nonmodifiable factors,
      such as severity of stroke, age, or premorbidity, but also by modifiable factors
      largely related to medical complications, such as infections and possibly
      sarcopenia. The highly successful concept of stroke units attests to the benefits
      of treating stroke comprehensively. Breakthroughs in improving outcome after
      stroke will only result from approaches that target not only the brain, but also
      systemic effects of stroke.

PMID- 22994218
TI  - The ischemic penumbra: how does tissue injury evolve?
AB  - An ischemic penumbra has the potential for functional recovery provided that
      local blood flow can be reestablished, but irreversible damage will develop
      without sufficient reperfusion, depending on the interaction of severity and
      duration of ischemia. With acute flows below the threshold required for
      maintenance of basic housekeeping, injury in the core is established within a few
      minutes. During the subacute phase, the irreversible damage expands into the
      penumbra: multiple electrical and biological signals are triggered by
      periinfarct, spreading depression-like depolarizations leading to hypoxia and
      stepwise increase in lactate. Usually within 6 to 8 hours, all the penumbra are
      converted into irreversible infarcts. In a delayed phase, secondary phenomena may
      cause additional tissue damage: disruption of the tight junctions results in
      vasogenic edema, leading to increase of water content and damage expansion.
      Neutrophils and cytokinins cause secondary inflammation, inducing further damage
      in periinfarct regions and connecting fiber tracts. Multimodal imaging might be
      able to differentiate among the tissue compartments affected by acute, subacute,
      or delayed ischemic damage, and thereby might provide the basis for phase
      specific treatment strategies.

PMID- 22994219
TI  - Current treatment of basilar artery occlusion.
AB  - Basilar artery occlusion (BAO) is associated with high mortality (85-95%) if
      recanalization does not occur. Evidence of the efficacy of different therapy
      protocols of intravenous thrombolysis (IVT) or intraarterial thrombolysis (IAT)
      and/or mechanical endovascular treatment is based on retrospective or prospective
      patient cohorts, since randomized controlled trials (RCTs) do not exist. Roughly
      a third of BAO patients reach independent outcome following thrombolysis. From
      those in whom recanalization occurs, about half will reach independence. In
      noninvasive and endovascular protocols, recanalization of BAO is reached in 60
      85% of the patients. While invasive endovascular approaches afford greater
      recanalization rates, they have not been proven superior to IVT in terms of
      functional outcome. Meaningful survival after BAO requires rapid access to
      thrombolysis. "Bridging" protocols have been introduced where rescue therapies
      such as endovascular thrombolysis and on-demand mechanical thrombectomy or
      angioplasty are used. Multimodal imaging techniques should be used to choose the
      best therapeutic option individually.

PMID- 22994220
TI  - Improving public education about stroke.
AB  - Stroke is a common and serious disease. Most studies have shown that basic public
      knowledge about what a stroke is, symptoms of a stroke, and the proper reaction
      to a stroke is quite deficient. The fact that a stroke affects cognitive,
      communicative, and motor functions may partially explain the poor reaction to
      acute stroke symptoms. Several educational studies, using diverse formats and
      messaging paradigms, have been shown to positively affect public knowledge of
      stroke symptoms. Such efforts have often used mass media public education
      campaigns with an emphasis on recognizing symptoms of an acute stroke. Some have
      been able to demonstrate an increase in the chance of patients (or by-standers)
      calling 911 and seeking emergency care. However, many programs were of brief
      duration, and their long-term benefits are uncertain. Continual educational
      efforts will be needed to improve stroke knowledge and increase the percentage of
      patients who seek emergency care.

PMID- 22994221
TI  - Impact of regional pre-hospital emergency medical services in treatment of
      patients with acute ischemic stroke.
AB  - Stroke is a major public health concern afflicting an estimated 795,000 Americans
      annually. The associated morbidity and mortality is staggering. Early treatment
      with thrombolytics is beneficial. The window for treatment is narrow and
      minimization of the time from symptom onset to treatment is vital. The general
      population is not well informed as to the warning signs or symptoms of stroke,
      leading to substantial delays in emergency medical services (EMS) activation.
      Ambulance transport of stroke patients to the hospital has demonstrated
      improvements in key benchmarks such as door to physician evaluation, door to CT
      initiation, and increased thrombolytic treatment. Pre-hospital notification of
      the impending arrival of a stroke patient allows for vital preparation in the
      treating emergency department, and improving timely evaluation and treatment upon
      arrival of the stroke patient. EMS systems are a vital component of the
      management of stroke patients, and resources used to improve these systems are
      beneficial.

PMID- 22994222
TI  - Techniques for improving efficiency in the emergency department for patients with
      acute ischemic stroke.
AB  - The past 15 years have witnessed significant strides in the management of acute
      stroke. The most significant advance, reperfusion therapy, has changed relatively
      little, but the integrated healthcare systems-stroke systems-established to
      effectively and safely administer stroke treatments have evolved greatly. Driving
      change is the understanding that "time is brain." Data are compelling that the
      likelihood of improvement is directly tied to time of reperfusion. Regional
      stroke systems of care ensure patients arrive at the most appropriate stroke
      capable hospital in which intrahospital systems have been created to process the
      potential stroke patient as quickly as possible. The hospital-based systems are
      comprised of prehospital care providers, emergency department physicians and
      nurses, stroke team members, and critical ancillary services such as neuroimaging
      and laboratory. Given their complexity, these systems of care require
      maintenance. Through teamwork and ownership of the process, more patients will be
      saved from potential death and long-term disability.

PMID- 22994223
TI  - Imaging-based selection in acute ischemic stroke trials - a quest for imaging
      sweet spots.
AB  - Ischemic stroke is a very heterogeneous disease that limits the efficacy of acute
      stroke treatments. Future trials will require advanced imaging to select patients
      for specific treatments. The most well-established imaging tools are the use of
      CT to exclude hemorrhage and diffusion-weighted MRI to demonstrate ischemia.
      While perfusion imaging is one option for patient selection, it has unresolved
      issues, including standardization and validation, that limit its value. As an
      alternative to mismatch when addressing stroke, one needs to know the size of the
      initial irreversible lesion (core), the presence and site/extent of occlusion
      (clot), and presence of leptomeningeal back filling and Willisian filling
      (collaterals). These can be summarized as the "3C" approach of core, clot, and
      collateral interpretation, which together can represent an imaging sweet spot,
      particularly for time-efficient endovascular treatment trial design.

PMID- 22994225
TI  - Treatment of acute ischemic stroke: systemic or local?
AB  - Systemic treatment of acute ischemic stroke currently means intravenous infusion
      of plasminogen activator in patients with the stroke syndrome after exclusion of
      brain hemorrhage irrespective of whether thrombotic arterial obstruction is
      present or not. In contrast, local intra-arterial treatment requires digital
      subtraction angiography and means direct treatment of the arterial pathology with
      the aim of recanalization and brain tissue reperfusion. Randomized controlled
      trials that test these two treatment approaches are missing. This paper discusses
      whether the time-saving systemic treatment approach is more promising for acute
      ischemic stroke patients than is the time-consuming endovascular local approach.

PMID- 22994226
TI  - How baseline severity affects efficacy and safety outcomes in acute ischemic
      stroke intervention trials.
AB  - Baseline severity of stroke may be an important predictor of efficacy and safety
      outcomes in acute stroke intervention trials. This summary explores definitions
      of baseline variables and outcomes used to measure stroke severity, efficacy, and
      safety. In addition, the discussion here reviews select acute ischemic stroke
      intravenous thrombolytic studies, such as the National Institute of Neurological
      Disorders and Stroke rt-PA Stroke Study and European Cooperative Acute Stroke
      Studies, select neuroprotectant and endovascular clot retrieval device studies,
      and large cooperative databases, such as the Virtual International Stroke Trials
      Archive and Safe Implementation of Treatment in Stroke-International Stroke
      Thrombolysis Registry, to explore relationships between baseline stroke severity
      and other possible factors associated with efficacy and safety outcomes. The NIH
      Stroke Scale and modified Rankin scale will be featured as major stroke outcome
      measures, based on frequency of use and reliability, familiarity, adaptability,
      and comparability.

PMID- 22994224
TI  - Considering hyperglycemia and thrombolysis in the Stroke Hyperglycemia Insulin
      Network Effort (SHINE) trial.
AB  - Hyperglycemia is associated with enhanced cortical toxicity and larger infarct
      volumes following focal cerebral ischemia. Initial blood glucose in acute
      ischemic stroke patients may also contribute to a differential response to
      thrombolysis (i.e., administration of tissue plasminogen activator (t-PA)) and
      affect risk of symptomatic intracerebral hemorrhage (sICH). The Stroke
      Hyperglycemia Insulin Network Effort (SHINE) study is a phase III single-blinded,
      randomized control trial comparing an intensive level of glucose control with
      standard of care glucose control in hyperglycemic stroke patients. In stratifying
      randomization by treatment with intravenous t-PA, the SHINE trial offers a unique
      opportunity to evaluate an association between euglycemic control and outcomes
      from stroke thrombolysis in a prospective, comparative study. We hypothesize that
      normalization of blood glucose in the acute stroke setting may reduce risk of
      thrombolysis-induced sICH. With enrollment recently underway, the stratified
      results from the SHINE trial could substantially influence future treatment
      decisions for hyperglycemic stroke patients.

PMID- 22994228
TI  - Safety and efficacy of 0.6 mg/kg rt-PA: optimum rt-PA dose revisited.
AB  - Although the internationally recommended dosage of alteplase, a single-chain rt
      PA, is 0.9 mg/kg, 0.6 mg/kg is the only approved dosage in Japan, and it is
      widely used there. Duteplase is a two-chain rt-PA, and based on findings of the
      duteplase trials in the early 1990s, the smaller dosage of 0.6 mg/kg of alteplase
      was tested in the Japan Alteplase Clinical Trial (J-ACT), which indicated that
      the efficacy/safety profile of this dose was comparable to the 0.9 mg/kg dosage
      used in other countries. The Japan Alteplase Clinical Trial II (J-ACT II) further
      demonstrated efficacy of 0.6 mg/kg alteplase with regard to vascular outcomes in
      patients with middle cerebral artery (MCA) occlusion. Finally, the Japan post
      Marketing Alteplase Registration Study (J-MARS) confirmed the efficacy/safety
      profile of 0.6 mg/kg alteplase in a clinical setting that was comparable to the
      dose of 0.9 mg/kg in the European counterpart, the Safe Implementation of
      Thrombolysis in Stroke-Monitoring Study (SITS-MOST). The dose of 0.6 mg/kg seems
      to be optimal, at least in far-east Asians, and might be extrapolated to other
      ethnic groups as well.

PMID- 22994229
TI  - Ancillary approaches to plasminogen activators.
AB  - Acute ischemic stroke develops from an interruption in focal cerebral blood flow.
      In many cases, it is caused by an acute thromboembolism. Although systemic
      fibrinolytic therapy for acute ischemic stroke has been a significant
      breakthrough in the management of this disease, additional agents and methods
      that could improve or restore cerebral flow are necessary. Similarly to findings
      in acute myocardial infarction, combination pharmacotherapy has the potential to
      improve current thrombolytic treatment in acute ischemic stroke. In recent years,
      research efforts were directed toward various combination therapy with
      pharmacological and nonpharmacological methods. Several trials tested tissue
      plasminogen activator (t-PA) in combination with antiplateletes and
      anticoagulants. Combination of t-PA with nonpharmacological agents included
      sonothrombolysis (amplifying the thrombolytic effect), laser (neuro-recovery),
      hypothermia (cytoprotection and decreasing brain swelling), and blood flow
      augmentation (increasing residual flow and recruitment of collateral vessels).
      This paper will review ongoing clinical trials and safety of these promising
      combinatory treatments.

PMID- 22994230
TI  - Selection of possible responders to thrombolytic therapy in acute ischemic
      stroke.
AB  - Ischemic stroke is one of the leading causes of death and morbidity worldwide,
      and systemic thrombolytic treatment is still the first-line therapy within 4.5 h
      from symptom onset. Selecting patients for treatment response is mandatory in any
      time window but challenging as well. The authors aim to support stroke physicians
      in their individual decision making. Besides evidence from clinical trials, some
      suggestions included here exclusively reflect the authors' opinions. This article
      presents clinical and imaging criteria of selecting patients reasonably, offering
      causal therapy to a growing number of patients.

PMID- 22994227
TI  - Does inhibiting Sur1 complement rt-PA in cerebral ischemia?
AB  - Hemorrhagic transformation (HT) associated with recombinant tissue plasminogen
      activator (rt-PA) complicates and limits its use in stroke. Here, we provide a
      focused review on the involvement of matrix metalloproteinase 9 (MMP-9) in rt-PA
      associated HT in cerebral ischemia, and we review emerging evidence that the
      selective inhibitor of the sulfonylurea receptor 1 (Sur1), glibenclamide (U.S.
      adopted name, glyburide), may provide protection against rt-PA-associated HT in
      cerebral ischemia. Glyburide inhibits activation of MMP-9, ameliorates edema
      formation, swelling, and symptomatic hemorrhagic transformation, and improves
      preclinical outcomes in several clinically relevant models of stroke, both
      without and with rt-PA treatment. A retrospective clinical study comparing
      outcomes in diabetic patients with stroke treated with rt-PA showed that those
      who were previously on and were maintained on a sulfonylurea fared significantly
      better than those whose diabetes was managed without sulfonylureas. Inhibition of
      Sur1 with injectable glyburide holds promise for ameliorating rt-PA-associated HT
      in stroke.

PMID- 22994231
TI  - Aging and the neurovascular unit.
AB  - With the demonstration that acute recanalization of obstructed symptomatic
      cerebral arteries during ischemic stroke can result in substantial improvement in
      clinical outcome, the variability in clinical responses, and in hemorrhagic
      transformation, requires attention. This short review addresses the effect of
      aging and amyloid deposition disease on microvessel integrity, interactions
      within the neurovascular unit, cerebral tissue susceptibility to ischemic injury,
      and postischemic inflammation, and ultimately on the outcomes and safety of acute
      recanalization during ischemic stroke. Microvessels and neighboring neurons
      respond simultaneously to focal ischemia. The cellular components and matrix
      barriers of the neurovascular unit all respond to ischemia; however, their
      coordinate interactions are not understood. Furthermore, there is little known
      about the cell-cell and cell-matrix interactions within the unit, or about the
      effect of beta-amyloid on microvessel responses during ischemia. These
      considerations indicate the need for a coordinated research effort to understand
      the origins of the variability in recanalization outcome.

PMID- 22994232
TI  - Intra-arterial vasodilator use during endovascular therapy for acute ischemic
      stroke might improve reperfusion rate.
AB  - Treatment of acute ischemic stroke (AIS) is an evolving field. New treatment
      options are still needed in order to achieve greater success rates for arterial
      recanalization. Intra-arterial therapy (lAT) is an option for AIS patients who
      are not good candidates for intravenous (i.v.) recombinant tissue plasminogen
      activator (rt-PA) or where it has failed. While good data establishing the role
      of IAT in AIS management are lacking, the potential clinical efficacy of IAT is
      based on the premise that recanalization and reperfusion may result in better
      clinical outcome. Although lAT recanalization and reperfusion rates of large
      vessel occlusion are much higher than they are for i.v. rt-PA, IAT's radiological
      efficacy is still far from perfect. Vasodilator use during IAT for AIS may
      increase the recanalization and reperfusion rates of such therapy. In this
      report, we describe the radiographic and clinical outcomes in a cohort of AIS
      patients who received intra-arterial (i.a.) vasodilators during IAT and summarize
      the role of i.a. vasodilators in the process of recanalization and reperfusion.

PMID- 22994233
TI  - Timing of thrombolysis for acute ischemic stroke: "timing is everything" or
      "everyone is different".
AB  - It is indisputable that in the first 2 to 3 hours of an acute ischemic, the best
      strategy to maximize recovery is robustly time-based and depends on getting the
      artery open as soon as possible. The second law of thermodynamics and the
      underappreciated effect of clot consistency and size must be accounted for in our
      efforts to minimize time to recanalization within the first 2 to 3 hours. It is
      also clear that at later time intervals, beyond 4.5 hours, few patients
      completely recover even with sustained complete recanalization, and that the
      ability to recover depends more on physiologic tissue issues than on the duration
      of the occlusion. Clinical factors as well as imaging should be used to select
      patients who may benefit from delayed attempts at reperfusion.

PMID- 22994234
TI  - Pre- and in-hospital intersection of stroke care.
AB  - Acute ischemic stroke is a time-critical emergency for which thrombolytic therapy
      is the only medical treatment. Many patients who would benefit from this
      treatment are deprived of it due to delays. Failure to call for help rapidly is
      the main obstacle, but even when the call is made in time, the prehospital
      evaluation, transportation, and emergency department (ED) diagnostics often take
      too long to treat the patient with thrombolysis. Interventions to reduce pre- and
      in-hospital delays have been described; although no single intervention is likely
      to make a major difference, a whole set of interventions needs to be implemented.
      The intersection of the pre- and in-hospital care is of special importance. With
      successful protocols and good communication between the emergency medical service
      and ED, delays can be significantly reduced. On the basis of our experience, 94%
      of patients can be treated within 60 min of arrival, based largely on using the
      prehospital time effectively.

PMID- 22994235
TI  - A strategic plan to accelerate development of acute stroke treatments.
AB  - In order to reenergize acute stroke research and accelerate the development of
      new treatments, we need to transform the usual design and conduct of clinical
      trials to test for small but significant improvements in effectiveness, and treat
      patients as soon as possible after stroke onset when treatment effects are most
      detectable. This requires trials that include thousands of acute stroke patients.
      A plan to make these trials possible is proposed. There are four components: (1)
      free access to the electronic medical record; (2) a large stroke emergency
      network and clinical trial coordinating center connected in real time to hundreds
      of emergency departments; (3) a clinical trial technology development center; and
      (4) strategic leadership to raise funds, motivate clinicians to participate, and
      interact with politicians, insurers, legislators, and other national and
      international organizations working to advance the quality of stroke care.

PMID- 22994238
TI  - New analysis workflow for MALDI imaging mass spectrometry: application to the
      discovery and identification of potential markers of childhood absence epilepsy.
AB  - Childhood absence epilepsy is a prototypic form of generalized nonconvulsive
      epilepsy characterized by short impairments of consciousness concomitant with
      synchronous and bilateral spike-and-wave discharges in the electroencephalogram.
      For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a
      genetic selection, constitute an original mouse model "in mirror" of absence
      epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the
      discovery of potential biomarkers is increasingly recognized. Interestingly,
      statistical analysis tools specifically adapted to IMS data sets and methods for
      the identification of detected proteins play an essential role. In this study, a
      new cross-classification comparative design using a combined discrete wavelet
      transformation-support vector machine classification was developed to
      discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z
      ratios were thus highlighted as potential markers with very high recognition
      rates (87-99%). Seven of these potential markers were identified using a top-down
      approach, in particular a fragment of Synapsin-I. This protein is yet suspected
      to be involved in epilepsy. Immunohistochemistry and Western Blot experiments
      confirmed the differential expression of Synapsin-I observed by IMS, thus tending
      to validate our approach. Functional assays are being performed to confirm the
      involvement of Synapsin-I in the mechanisms underlying childhood absence
      epilepsy.

PMID- 22994237
TI  - Excessive proinflammatory cytokine and chemokine responses of human monocyte
      derived macrophages to enterovirus 71 infection.
AB  - BACKGROUND: The levels of proinflammatory cytokine or chemokine in blood and
      cerebrospinal fluid are thought to be one of predictors for clinical severity of
      enterovirus 71 (EV71) infection, yet the cellular sources or signalling mechanism
      remain undefined. Here, we focused on the response of human primary monocyte
      derived macrophages (MDMs) to EV71 virus and its possible mechanisms. METHODS:
      Human primary MDMs were infected by EV71 virus in vitro. Infectivity and viral
      replication were assayed, and cytokine responses were determined by Cytometric
      Bead Array(CBA) analysis. The relative changes of Toll-like receptors, retinoic
      acid-inducible gene I (RIG-I) and melamoma differentiation associated gene 5
      (MDA5) mRNA expression were detected by real-time RT-PCR. RESULTS: Effective
      infection and viral replication were detected in EV71-infected MDMs. The titters
      of progeny virus released from EV71-infected MDMs gradually increased from 6-h to
      48-h point of infection (POI.). Proinflammatory cytokines: IL-1, IL-6, TNF-alpha
      but not IFN-alpha and gamma were induced in MDMs by EV71. EV71 infection
      significantly increased the release of IL-8, IP-10 and RANTES at 12-h or 24-h
      POI. Upregulation of TLR2, TLR7 and TLR8 mRNA expression rather than TLR3, TLR4,
      TLR6, TLR9, TLR10, RIG-I, MDA5 were found at different time points in EV71
      infected MDMs. CONCLUSIONS: Our findings suggested that macrophages are not only
      the important target cells but also the effectors during EV71 infection, and they
      may play an important role in the pathogenesis of EV71 infection. And the
      proinflammatory cytokine and chemokine responses in EV71-infected MDMs may be
      mediated by the activation of differential pattern of TLRs.

PMID- 22994240
TI  - Dynamic surface enhanced Raman spectroscopy (SERS): extracting SERS from normal
      Raman scattering.
AB  - We have demonstrated two significant benefits of dynamic surface enhanced raman
      spectroscopy (DSERS) measurements: removal of instrumental and normal Raman
      interferences in surface enhanced raman spectroscopy (SERS) spectroscopy and site
      selective spectroscopy of adsorbate populations on SERS-active particles. Our
      first example of shelled nanoparticles at very low concentrations confirmed the
      benefit of DSERS for removal of an overwhelmingly strong solvent spectral
      interference. The second benefit, site selection, was demonstrated with 4
      mercaptopyridine on bare Au nanoparticles to observe a small population of
      molecules that were spectroscopically unique from the large population of
      molecules on the particles. The DSERS spectrum originated from excess variance
      between a small population of adsorbates on the ensemble of nanoparticles.

PMID- 22994241
TI  - High-resolution spectroscopy and structure of osmium tetroxide. A benchmark study
      on 192OsO4.
AB  - Osmium tetroxide (OsO(4)) is a heavy tetrahedral molecule that constitutes a
      benchmark for quantum chemistry calculations. Its favorable spin statistics (due
      to the zero nuclear spin of oxygen atoms) is such that only A(1) and A(2) (T(d)
      symmetry) rovibrational levels are allowed, leading to a dense but quite easily
      resolvable spectrum. We reinvestigate here the nu(1)/nu(3) stretching fundamental
      (940-980 cm(-1)) dyad region and perform new assignments and effective
      Hamiltonian parameter fits for the main isotopologue ((192)OsO(4)). We also
      investigate the nu(2)/nu(4) bending fundamental dyad (300-360 cm(-1)) for the
      first time and perform a preliminary analysis. New experimental data have been
      obtained at 0.001 cm(-1) resolution using an isotopically pure (192)OsO(4) sample
      and the Synchrotron SOLEIL light source. Assignments and analyses were performed
      using SPVIEW and XTDS software, respectively. We provide precise effective
      Hamiltonian parameters, including the band centers for all of the fundamental
      levels and rotational constants for the ground state and for all four fundamental
      levels. We discuss isotopic shifts, estimate the equilibrium rotational constant
      B(e), and derive a precise value for the equilibrium bond length r(e)(Os-O) =
      1.70919(16) A. We also performed experiments to measure for the first time the IR
      integrated intensities for the nu(2)/nu(4) bending fundamental dyad. These new
      data are compared to current ab initio predictions.

PMID- 22994242
TI  - Numerical simulation of the effect of permeability on the hydrodynamics in a
      parallel-plate coculture flow chamber.
AB  - To study the effect of the porous membrane permeability on the hydrodynamics in a
      parallel-plate coculture flow chamber (PPcFC), we demonstrated the permeability
      of the porous membrane as a function of some parameters, such as porosity,
      membrane thickness, pore size and shape of the membrane. The effect of
      permeability on the flow in the PPcFC was analysed using the commercial software 
      Fluent. Results showed that the permeability was directly proportional to the
      thickness, the porosity and the pore size of the membrane, and inversely
      proportional to the surface shape factor. To ensure the best flow pattern, the
      inlet velocity range was limited by the membrane permeability and fluid
      viscosity, and then restricted the available magnitudes of shear rate on the
      permeable membrane. Our findings are helpful in designing and preparing the
      biomaterials that have adequate mechanical properties for the functional vascular
      grafts production, and in using of the flow chamber in various investigations. 

PMID- 22994243
TI  - Unusual malpositioning of hemodialysis catheter into the hepatic veins.
AB  - Malpositioning of long-term hemodialysis catheter is a known complication that
      may lead to a gradual decline in blood flow. We report two rare catheter
      malpositions in the hepatic veins in two patients with end-stage renal disease in
      whom a dialysis catheter was inserted through the left external jugular vein and
      the right external jugular vein. Because of gradual reduction of catheters' blood
      flow, an angiography was performed, which confirmed catheters' tip positioning
      into the hepatic veins. The catheters were replaced in the correct site.

PMID- 22994244
TI  - Domain wall geometry controls conduction in ferroelectrics.
AB  - A new paradigm of domain wall nanoelectronics has emerged recently, in which the
      domain wall in a ferroic is itself an active device element. The ability to
      spatially modulate the ferroic order parameter within a single domain wall allows
      the physical properties to be tailored at will and hence opens vastly unexplored
      device possibilities. Here, we demonstrate via ambient and ultrahigh-vacuum (UHV)
      scanning probe microscopy (SPM) measurements in bismuth ferrite that the
      conductivity of the domain walls can be modulated by up to 500% in the spatial
      dimension as a function of domain wall curvature. Landau-Ginzburg-Devonshire
      calculations reveal the conduction is a result of carriers or vacancies migrating
      to neutralize the charge at the formed interface. Phase-field modeling indicates
      that anisotropic potential distributions can occur even for initially uncharged
      walls, from polarization dynamics mediated by elastic effects. These results are
      the first proof of concept for modulation of charge as a function of domain wall
      geometry by a proximal probe, thereby expanding potential applications for oxide
      ferroics in future nanoscale electronics.

PMID- 22994245
TI  - The description and host-parasite relationships of a new quadrigyrid species
      (Acanthocephala) from the Persian tooth-carp, Aphanius farsicus (Actinoptreygii:
      Cyprinodontidae) in Iran.
AB  - Acanthogyrus (Acanthosentis) barmeshoori n. sp. (Quadrigyridae) is described from
      the Persian tooth-carp, Aphanius farsicus Teimori, Esmaeili, and Reichenbacher,
      2011 (Cyprinodontidae) in the Maharlu Lake basin, southern Iran. Aphanius
      farsicus is an endemic freshwater fish found in streams and springs that drain
      into Maharlu Lake, Shiraz, Iran. The new species is the smallest of all the 44
      known species of the subgenus Acanthosentis Verma and Datta, 1929, measuring
      between 0.26 and 1.68 mm in length. It is further distinguished by having a short
      cylindrical proboscis with very long anterior hooks widely separated from very
      small hooks in 2 very close circles posteriorly (hook length ratio about 4:1). It
      is separated from 4 other species of Acanthosentis with similar proboscis
      armature but with less-extreme diversification of hook length. The new species is
      also distinguished in having anterior para-receptacle structures (PRS) and a
      similar posterior structure like those reported in only 1 other species of
      Acanthosentis from Japan. Proboscis receptacle is single walled with a large
      triangular cephalic ganglion. Testes are large, pre-equatorial, and Saefftigen's
      pouch is prominent. Fourteen to 25 circles of spines cover the anterior 50-70% of
      the trunk, but a few spines may be present at posterior end of trunk. This is the
      first species of Acanthosentis where SEM images, showing external morphological
      details, are provided. From a total of 357 fish specimens examined between July
      2006 and June 2007, 173 specimens (48.5%) were infected with individuals of the
      new species. The prevalence of infection decreased with increasing fish size. The
      parasite was observed all year, with the highest abundance and intensity in May
      while the prevalence was highest in February. The prevalence of acanthocephalans
      decreased with increasing fish size. While most worms were recovered in fish
      within the length range of 18-29.9 mm, 1 of the longest parasites (1.68 mm long)
      was found in fish within the range of 30-33.9 mm long.

PMID- 22994246
TI  - Structural, optical, and dielectric properties of Bi(1.5-x)Zn(0.92
      y)Nb(1.5)O(6.92-delta) thin films grown by PLD on R-plane sapphire and LaAlO3
      substrates.
AB  - Bi(1.5-x)Zn(0.92-y)Nb(1.5)O(6.92-delta) thin films have the potential to be
      implemented in microwave devices. This work aims to establish the effect of the
      substrate and of the grain size on the optical and dielectric properties. Bi(1.5
      x)Zn(0.92-y)Nb(1.5)O(6.92-delta) thin films were grown at 700  degrees C via
      pulsed-laser deposition on R-plane sapphire and (100)(pc) LaAlO(3) substrates at
      various oxygen pressures (30, 50, and 70 Pa). The structure, morphology,
      dielectric and optical properties were investigated. Despite bismuth and zinc
      deficiencies, with respect to the Bi(1.5)Zn(0.92)Nb(1.5)O(6.92) stoichiometry,
      the films show the expected cubic pyrochlore structure with a (100) epitaxial
      like growth. Different morphologies and related optical and dielectric properties
      were achieved, depending on the substrate and the oxygen pressure. In contrast to
      thin films grown on (100)(pc) LaAlO(3), the films deposited on R-plane sapphire
      are characterized by a graded refractive index along the layer thickness. The
      refractive index (n) at 630 nm and the relative permittivity (epsilon(r))
      measured at 10 GHz increase with the grain size: on sapphire, n varies from 2.29
      to 2.39 and epsilon(r) varies from 85 to 135, when the grain size increases from
      37 nm to 77 nm. On the basis of this trend, visible ellipsometry can be used to
      probe the characteristics in the microwave range quickly, nondestructively, and
      at a low cost.

PMID- 22994248
TI  - Availability of over-the-counter emergency contraception in 2 disparate New York
      City neighborhoods.
AB  - We conducted a telephone survey of pharmacies in 2 New York City neighborhoods on
      same-day availability, type, and cost of over-the-counter emergency
      contraception. There was no difference in availability of over-the-counter
      emergency contraception between Upper East Side and East Harlem pharmacies (93%
      vs 94%; P = .71). Average cost of medication was less in East Harlem than in the
      Upper East Side ($45.16 vs $51.64; P < .001). Efforts should accentuate
      overcoming cost and knowledge barriers associated with the use of emergency
      contraception.

PMID- 22994247
TI  - Meta-analysis of single-session behavioral interventions to prevent sexually
      transmitted infections: implications for bundling prevention packages.
AB  - Evidence-based, single-session behavioral interventions are urgently needed for
      preventing the spread of HIV and other sexually transmitted infections (STIs). To
      estimate the efficacy of single-session, behavioral interventions for STI
      prevention, we collected data from 29 single-session interventions (20 studies; n
      = 52 465) with an STI outcome. Infection with an STI was 35% less likely (odds
      ratio = 0.65; 95% confidence interval = 0.55-0.77) among intervention group
      participants than among control group participants. Single-session interventions
      offer considerable benefits in terms of disease prevention and create minimal
      burden for both the patient and the provider. Brief and effective STI prevention
      interventions are a valuable tool and can be readily adapted to bolster the
      benefits of biomedical technologies focusing on the prevention of HIV and other
      STIs.

PMID- 22994249
TI  - Integration of primary health care and public health during a public health
      emergency.
AB  - We have provided a detailed evaluation of how collaboration between an Ontario
      public health unit and its primary care providers facilitated an optimal response
      to the 2009 H1N1 influenza pandemic.  Family health teams (integrated,
      interdisciplinary teams that provide a range of care options) provided flu
      assessment centers, with public health as a partner providing infection control
      advice, funding, coordination, antiviral medication, clinical care guidelines,
      supplemental nurse staffing, and arrangement of communication strategies with the
      public.  The family health team structure offers a new capacity for timely,
      coordinated, and comprehensive response to public health emergencies, in
      partnership with public health, and provides a promising new direction for
      healthcare organization.

PMID- 22994250
TI  - Improving population health through integration of primary care and public
      health: providing access to physical activity for community health center
      patients.
AB  - OBJECTIVES: Our community health center attempted to meet public health goals for
      encouraging exercise in adult patients vulnerable to obesity, diabetes,
      hypertension, and other chronic diseases by partnering with a local YMCA.
      METHODS: During routine office visits, providers referred individual patients to
      the YMCA at no cost to the patient. After 2 years, the YMCA instituted a $10 per
      month patient copay for new and previously engaged health center patients.
      RESULTS: The copay policy change led to discontinuation of participation at the
      YMCA by 80% of patients. Patients who persisted at the YMCA increased their
      visits by 50%; however, more men than women became frequent users after
      institution of the copay. New users after the copay were also more likely to be
      younger men. Thus the copay skewed the population toward a younger group of men
      who exercised more frequently. Instituting a fee appeared to discourage more
      tentative users, specifically women and older patients who may be less physically
      active. CONCLUSIONS: Free access to exercise facilities (rather than self-paid
      memberships) may be a more appropriate approach for clinicians to begin engaging
      inexperienced or uncertain patients in regular fitness activities to improve
      health.

PMID- 22994251
TI  - The impact of a free older persons' bus pass on active travel and regular walking
      in England.
AB  - OBJECTIVES: We assessed the potential public health benefit of the National Bus
      Pass, introduced in 2006, which permits free local bus travel for older adults
      (>= 60 years) in England. METHODS: We performed regression analyses with annual
      data from the 2005-2008 National Travel Survey. Models assessed associations
      between being a bus pass holder and active travel (walking, cycling, and use of
      public transport), use of buses, and walking 3 or more times per week. RESULTS:
      Having a free pass was significantly associated with greater active travel among
      both disadvantaged (adjusted odds ratio [AOR] = 4.06; 95% confidence interval
      [CI] = 3.35, 4.86; P < .001) and advantaged groups (AOR = 4.72; 95% CI = 3.99,
      5.59; P < .001); greater bus use in both disadvantaged and advantaged groups (AOR
      = 7.03; 95% CI = 5.53, 8.94; P < .001 and AOR = 7.11; 95% CI = 5.65, 8.94; P <
      .001, respectively); and greater likelihood of walking more frequently in the
      whole cohort (AOR = 1.15; 95% CI = 1.07, 1.12; P < .001). CONCLUSIONS: Public
      subsidies enabling free bus travel for older persons may confer significant
      population health benefits through increased incidental physical activity.

PMID- 22994252
TI  - Visiting the emergency department for dental problems: trends in utilization,
      2001 to 2008.
AB  - OBJECTIVES: We tested the hypothesis that between 2001 and 2008, Americans
      increasingly relied upon emergency departments (EDs) for dental care. METHODS:
      Data from 2001 through 2008 were collected from the National Hospital Ambulatory
      Medical Care Survey (NHAMCS). Population-based visit rates for dental problems,
      and, for comparison, asthma, were calculated using annual US Census Bureau
      estimates. As part of the analysis, we described patient characteristics
      associated with large increases in ED dental utilization. RESULTS: Dental visit
      rates increased most dramatically for the following subpopulations: those aged 18
      to 44 years (7.2-12.2 per 1000, P < .01); Blacks (6.0-10.4 per 1000, P < .01);
      and the uninsured (9.5-13.2 per 1000, P < .01). Asthma visit rates did not change
      although dental visit rates increased 59% from 2001 to 2008. CONCLUSIONS: There
      is an increasing trend in ED visits for dental issues, which was most pronounced
      among those aged 18 to 44 years, the uninsured, and Blacks. Dental visit rates
      increased significantly although there was no overall change in asthma visit
      rates. This suggests that community access to dental care compared with medical
      care is worsening over time.

PMID- 22994253
TI  - Innovative primary care training: the Cambridge Health Alliance Oral Physician
      Program.
AB  - We evaluated the Oral Physician Program, a dental residency sponsored by Harvard
      Medical School, Harvard School of Dental Medicine, and the Cambridge Health
      Alliance that offers an innovative model for training dentists to provide limited
      primary care. The didactic and clinical experiences increased residents' medical
      knowledge and interviewing skills, and faculty assessments supported their role
      as oral physicians. Oral physicians could increase patients'-especially patients
      from underserved groups-access to integrated oral and primary care services.

PMID- 22994255
TI  - Household food insecurity during childhood and subsequent health status: the
      early childhood longitudinal study--kindergarten cohort.
AB  - OBJECTIVES: We examined long-term patterns of household food insecurity in
      children from kindergarten through eighth grade and the association between those
      patterns and children's proxy-reported health status in eighth grade. METHODS: We
      obtained data from the Early Childhood Longitudinal Study-Kindergarten Cohort, a
      study that followed a nationally representative sample of students from
      kindergarten entry in 1998-1999 through eighth grade. We classified food
      insecurity according to the number of years of reported household food insecurity
      over 4 observation years. We estimated logistic regression models to estimate the
      association between cumulative food insecurity exposure and health outcomes.
      RESULTS: Food insecurity was generally a transient rather than a persistent
      condition. Persistent food insecurity over the 9-year period was associated with
      lower health status in eighth grade, whereas more transient food insecurity was
      not significantly associated with health outcomes in most models. CONCLUSIONS:
      Single-year estimates substantially underestimate the share of children whose
      households experienced food insecurity at some point during their childhood
      years. Persistent food insecurity is an important public health issue for
      children. Policy interventions to alleviate children's persistent food insecurity
      may promote child health.

PMID- 22994254
TI  - Primary care and public health services integration in Brazil's unified health
      system.
AB  - OBJECTIVES: We examined associations between transdisciplinary collaboration,
      evidence-based practice, and primary care and public health services integration
      in Brazil's Family Health Strategy. We aimed to identify practices that
      facilitate service integration and evidence-based practice. METHODS: We collected
      cross-sectional data from community health workers, nurses, and physicians (n =
      262). We used structural equation modeling to assess providers' service
      integration and evidence-based practice engagement operationalized as latent
      factors. Predictors included endorsement of team meetings, access to and
      consultations with colleagues, familiarity with community, and previous research
      experience. RESULTS: Providers' familiarity with community and team meetings
      positively influenced evidence-based practice engagement and service integration.
      More experienced providers reported more integration and engagement. Physicians
      reported less integration than did community health workers. Black providers
      reported less evidence-based practice engagement than did Pardo (mixed races)
      providers. After accounting for all variables, evidence-based practice engagement
      and service integration were moderately correlated. CONCLUSIONS: Age and race of
      providers, transdisciplinary collaboration, and familiarity with the community
      are significant variables that should inform design and implementation of
      provider training. Promising practices that facilitate service integration in
      Brazil may be used in other countries.

PMID- 22994257
TI  - The dissimilarity of species interaction networks.
AB  - In a context of global changes, and amidst the perpetual modification of
      community structure undergone by most natural ecosystems, it is more important
      than ever to understand how species interactions vary through space and time. The
      integration of biogeography and network theory will yield important results and
      further our understanding of species interactions. It has, however, been hampered
      so far by the difficulty to quantify variation among interaction networks. Here,
      we propose a general framework to study the dissimilarity of species interaction
      networks over time, space or environments, allowing both the use of quantitative
      and qualitative data. We decompose network dissimilarity into interactions and
      species turnover components, so that it is immediately comparable to common
      measures of beta-diversity. We emphasise that scaling up beta-diversity of
      community composition to the beta-diversity of interactions requires only a small
      methodological step, which we foresee will help empiricists adopt this method. We
      illustrate the framework with a large dataset of hosts and parasites interactions
      and highlight other possible usages. We discuss a research agenda towards a
      biogeographical theory of species interactions.

PMID- 22994256
TI  - Leading causes of unintentional and intentional injury mortality: United States,
      2000-2009.
AB  - OBJECTIVES: We have described national trends for the 5 leading external causes
      of injury mortality. METHODS: We used negative binomial regression and annual
      underlying cause-of-death data for US residents for 2000 through 2009. RESULTS:
      Mortality rates for unintentional poisoning, unintentional falls, and suicide
      increased by 128%, 71%, and 15%, respectively. The unintentional motor vehicle
      traffic crash mortality rate declined 25%. Suicide ranked first as a cause of
      injury mortality, followed by motor vehicle traffic crashes, poisoning, falls,
      and homicide. Females had a lower injury mortality rate than did males. The
      adjusted fall mortality rate displayed a positive age gradient. Blacks and
      Hispanics had lower adjusted motor vehicle traffic crash and suicide mortality
      rates and higher adjusted homicide rates than did Whites, and a lower unadjusted
      total injury mortality rate. CONCLUSIONS: Mortality rates for suicide, poisoning,
      and falls rose substantially over the past decade. Suicide has surpassed motor
      vehicle traffic crashes as the leading cause of injury mortality. Comprehensive
      traffic safety measures have successfully reduced the national motor vehicle
      traffic crash mortality rate. Similar efforts will be required to diminish the
      burden of other injury.

PMID- 22994258
TI  - Discovery of new antagonists aimed at discriminating UII and URP-mediated
      biological activities: insight into UII and URP receptor activation.
AB  - BACKGROUND AND PURPOSE: Recent evidence suggested that urotensin II (UII) and its
      paralog peptide UII-related peptide (URP) might exert common but also divergent
      physiological actions. Unfortunately, none of the existing antagonists were
      designed to discriminate specific UII- or URP-associated actions, and our
      understanding, on how these two endogenous peptides can trigger different, but
      also common responses, is limited. EXPERIMENTAL APPROACH: Ex vivo rat and monkey
      aortic ring contraction as well as dissociation kinetics studies using
      transfected CHO cells expressing the human urotensin (UT) receptors were used in
      this study. KEY RESULTS: Ex vivo rat and monkey aortic ring contraction studies
      revealed the propensity of [Pep(4)]URP to decrease the maximal response of human
      UII (hUII) without any significant change in potency, whereas no effect was
      noticeable on the URP-induced vasoconstriction. Dissociation experiments
      demonstrated the ability of [Pep(4)]URP to increase the dissociation rate of
      hUII, but not URP. Surprisingly, URP, an equipotent UII paralog, was also able to
      accelerate the dissociation rate of membrane-bound (125)I-hUII, whereas hUII had
      no noticeable effect on URP dissociation kinetics. Further experiments suggested
      that an interaction between the glutamic residue at position 1 of hUII and the UT
      receptor seems to be critical to induce conformational changes associated with
      agonistic activation. Finally, we demonstrated that the N-terminal domain of the
      rat UII isoform was able to act as a specific antagonist of the URP-associated
      actions. CONCLUSION: Such compounds, that is [Pep(4)]URP and rUII(1-7), should
      prove to be useful as new pharmacological tools to decipher the specific role of
      UII and URP in vitro but also in vivo.

PMID- 22994260
TI  - Maternal recall of birthweight and birth size in Entebbe, Uganda.
AB  - OBJECTIVES: To assess the reliability of maternally recalled birthweight and size
      in Entebbe, Uganda. METHODS: The study population comprised 404 mothers, who were
      participants in the Entebbe Mother and Baby Study (EMaBS). Mothers were recruited
      to EMaBS during antenatal care, maternal characteristics were recorded during
      pregnancy, and birthweight was recorded at delivery. Four to seven years after
      delivery, mothers were asked to recall the child's birthweight and size. Their
      responses were compared with the birthweight recorded in the EMaBS database.
      RESULTS: Of 404 interviewed mothers, 303 (75%) were able to give an estimate of
      birthweight and for 265 of these EMaBS data on recorded birthweights were
      available. Women who were educated and whose children had low birth order were
      more likely to be able to give an estimate: 37 (14%) recalled the exact recorded
      birthweight; a further 52 (20%) were accurate to within 0.1 kg of the recorded
      weight. On average, mothers overestimated birthweight by 0.06 kg (95% CI: 0.00
      0.13 kg, P = 0.04). Recalled and recorded birthweights showed moderate agreement
      with an intraclass correlation coefficient of 0.64. Four hundered mothers gave an
      estimate of birth size: the sensitivity and specificity of recalled birth size
      for classifying low birthweight were 76% (95% CI: 50-93%) and 70% (95% CI: 65
      75%), respectively. CONCLUSIONS: Mothers' recall of birthweight was not precise
      but in absence of other data, recall of birthweight and size may have some value
      in epidemiological studies in these settings.

PMID- 22994261
TI  - Identification of a novel HLA-A allele HLA-A*02:227N.
AB  - The HLA-A*02:227N allele differs from the closest matching allele A*02:01:01:01
      by one nucleotide substitution in exon 3 at nt 610 (C->T).

PMID- 22994262
TI  - Erythema multiforme in a 25-day old neonate.
AB  - Erythema multiforme is an acute, self-limiting, mucocutaneous hypersensitivity
      reaction characterized by distinctive target lesions. Most cases have been
      attributed to infection. Erythema multiforme occurs mainly in young adults and is
      extremely rare during the neonatal period. We report a 25-day-old girl who
      presented with target skin lesions on both the palms and soles with no other
      associated symptoms. She had no remarkable maternal, birth, or past medical
      history. Complete blood count, urinalysis, chest radiography, and herpes simplex
      virus 1 and 2 immunoglobulin G (IgG) titers revealed no abnormalities. Pathologic
      examination showed vacuolar interface change and dyskeratotic cells in the
      epidermis consistent with erythema multiforme. This unusual case emphasizes the
      importance of recognizing diagnostic clues in examining patients. Even in the
      presence of uncharacteristic factors, the typical target lesions of erythema
      multiforme are distinctive. 

PMID- 22994264
TI  - Fluoroscopic contralateral oblique view in interlaminar interventions: a
      technical note.
AB  - OBJECTIVE: To describe the value and utility in using a contralateral oblique
      (CLO) view when performing cervical, thoracic, and lumbar interlaminar procedures
      including epidural steroid injections and spinal cord stimulation percutaneous
      lead placement. METHODS AND RESULTS: Fluoroscopic images are used to illustrate
      the value of using CLO views. The CLO view is obtained after the level is
      confirmed. Then, the fluoroscope is obliqued contralateral to the needle tip to
      visualize the target interlaminar space and the spinolaminar line. In this
      fluoroscopic setup, the needle can be seen traversing between the superior and
      inferior lamina (elliptical appearing structures on CLO view) with the needle tip
      directed toward the spinolaminar line. The needle is then advanced through the
      ligamentum flavum into the posterior epidural space. The CLO view helps better
      visualize needle tip placement when patient positioning, body habitus, or other
      atypical anatomy makes visualization in standard lateral views challenging. The
      CLO provides more consistent visualization of the target structures. CONCLUSIONS:
      We recommend that the CLO view for thoracic and lumbar interlaminar procedures,
      in addition to cervical cases. Thus, when confirming proper needle placement for
      interlaminar procedures, the CLO view combined with anterior-posterior view
      yields safe multi-planar imaging and should be considered when a lateral view is
      unable to demonstrate target landmarks clearly.

PMID- 22994263
TI  - Sir David Jack: an extraordinary drug discoverer and developer.

PMID- 22994265
TI  - Immunohistochemical and molecular genetics study of a granular cell astrocytoma:
      a case report of malignant transformation to a glioblastoma.
AB  - We treated a 56-year-old woman who had a right temporal lobe tumor found by
      chance after a traffic accident. MRI confirmed a heterogeneously enhanced tumor
      in the temporal lobe with large peritumoral edema extending to the superior
      parietal lobe. The patient underwent tumor resection. The tumor consisted largely
      of distinct cells with discrete borders and granular cytoplasm. In granular
      cells, the accumulation of PAS-positive granules was observed.
      Immunohistochemical analysis demonstrated positive staining for GFAP, S-100, and
      oligodendrocyte transcription factor 2 and negative staining for synaptophysin.
      CD68 was negative in granular cells, but positive in stromal cells. Ki-67
      labeling index was quite low. The tumor was diagnosed as a granular cell
      astrocytoma (GCA). Postoperative radiotherapy combined with temozolomide was
      administered. One month after chemoradiotherapy, the tumor occurred in the
      parietal lobe, and a tumorectomy was performed. The tumor was composed of poorly
      differentiated astrocytic tumor cells with prominent microvascular proliferation
      and necrosis. A small number of granular cells were locally observed and the
      tumor was diagnosed as a glioblastoma. O6-methylguanine-DNA methyltransferase
      promoter methylation was detected in the GCA but not in the glioblastoma.
      Isocitrate dehydrogenase mutations were not detected in either tumor. Comparative
      genomic hybridization analysis demonstrated that no chromosomal abnormality was
      found in the GCA; however, a gain of chromosomes 7 and 19 and a loss of
      chromosomes 10 and 9p21 (CDKN2A) were found in the glioblastoma. p53 was strongly
      expressed in both the GCA and glioblastoma. The tumor progressed despite
      extensive chemotherapy, and the patient died 1 year after the initial treatment.
      Our immunohistochemical, genetic and chromosomal analyses indicate that the
      glioblastoma was transformed from the GCA.

PMID- 22994266
TI  - Controlling the kinetics of interferon transgene expression for improved gene
      therapy.
AB  - Interferon (IFN) gene based therapy has been studied for the treatment of many
      diseases such as viral infections, cancer and allergic diseases. Non-viral
      vectors, like plasmid DNA, are promising ways for delivering IFN genes, because
      of their low immunogenicity and toxicity compared with viral vectors. Potent
      therapeutic effects of IFN gene transfer will depend on the level and duration of
      transgene expression after in vivo administration. Therefore, controlling the
      kinetics of transgene expression of IFNs is a rational approach for improved gene
      therapy. The design and optimization of plasmid vectors, as well as their
      route/method of administration, is the key to obtaining high and persistent
      transgene expression. In this review, we aim to present experimental evidence
      about the relationships among the properties of plasmid vectors expressing IFNs,
      the kinetics of transgene expression, and therapeutic effects as well as safety
      issues.

PMID- 22994267
TI  - On the spatial scale of dispersal in coral reef fishes.
AB  - Marine biologists have gone through a paradigm shift, from the assumption that
      marine populations are largely 'open' owing to extensive larval dispersal to the
      realization that marine dispersal is 'more restricted than previously thought'.
      Yet, population genetic studies often reveal low levels of genetic structure
      across large geographic areas. On the other side, more direct approaches such as
      mark-recapture provide evidence of localized dispersal. To what extent can direct
      and indirect studies of marine dispersal be reconciled? One approach consists in
      applying genetic methods that have been validated with direct estimates of
      dispersal. Here, we use such an approach-genetic isolation by distance between
      individuals in continuous populations-to estimate the spatial scale of dispersal
      in five species of coral reef fish presenting low levels of genetic structure
      across the Caribbean. Individuals were sampled continuously along a 220-km
      transect following the Mesoamerican Barrier Reef, population densities were
      estimated from surveys covering 17 200 m(2) of reef, and samples were genotyped
      at a total of 58 microsatellite loci. A small but positive isolation-by-distance
      slope was observed in the five species, providing mean parent-offspring dispersal
      estimates ranging between 7 and 42 km (CI 1-113 km) and suggesting that there
      might be a correlation between minimum/maximum pelagic larval duration and
      dispersal in coral reef fishes. Coalescent-based simulations indicate that these
      results are robust to a variety of dispersal distributions and sampling designs.
      We conclude that low levels of genetic structure across large geographic areas
      are not necessarily indicative of extensive dispersal at ecological timescales.

PMID- 22994268
TI  - Topical Ranibizumab inhibits inflammatory corneal hem- and lymphangiogenesis.
AB  - PURPOSE: Ranibizumab (Lucentis((r)) ) is a Fab-Fragment of a recombinant,
      humanized, monoclonal VEGF (anti-vascular endothelial growth factor) antibody.
      This study analyzed the ability of topical Ranibizumab to inhibit
      lymphangiogenesis in addition to hemangiogenesis after acute corneal inflammation
      in vivo. In addition, the effect of Ranibizumab on the proliferation of human
      lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) in vitro
      was studied. METHODS: The inhibitory effect of Ranibizumab on LECs and BECs was
      studied in vitro using a proliferation enzyme-linked immunosorbent assay (ELISA)
      assay. To study the in vivo effects of Ranibizumab, the mouse model of suture
      induced inflammatory corneal neovascularization was used. Study mice received
      topical Ranibizumab as eye drops. After 1 week excised corneas were stained with
      LYVE-1 and CD31. Hemangiogenesis and lymphangiogenesis were analyzed
      morphometrically by using a semiautomatic method based on the image analyzing
      program Cell^F. RESULTS: An antiproliferative effect of Ranibizumab was seen in
      vitro on both human BECs and LECs with a significance of p < 0.0001 and p <
      0.0004, respectively. In vivo experiments showed that topical application of
      Ranibizumab significantly inhibits both hemangiogenesis (p = 0.0026) and
      lymphangiogenesis (p = 0.0026) in the cornea. CONCLUSION: Ranibizumab is a potent
      inhibitor of inflammatory corneal hemangiogenesis and lymphangiogenesis in vivo
      with a direct inhibitory effect on both endothelial cell types in vitro. This
      study for the first time demonstrates an inhibitory effect of Ranibizumab on
      lymphatic vessels which could have a wider range of clinical applications.

PMID- 22994269
TI  - Recent increase in allergic reactions to
      methylchloroisothiazolinone/methylisothiazolinone: is methylisothiazolinone the
      culprit?
AB  - BACKGROUND: The frequency of sensitization to methylchloroisothiazolinone (MCI)/
      methylisothiazolinone (MI) observed in the Information Network of Departments of
      Dermatology (IVDK) was constantly around 2.1% from 1998 to 2009. After that, it
      increased to 3.9% in 2011, paralleled by an increase in the frequency of allergic
      reactions to MI in the preservative series from 1.9% in 2009 to 4.4% in 2011. MI
      without MCI has increasingly been used as a preservative in cosmetics and skin
      care products in recent years. OBJECTIVES: To epidemiologically investigate the
      possible reasons for this development and to analyse concomitant reactions to
      MCI/MI and MI. METHODS: A retrospective analysis of IVDK data from 2009 to 2011
      was performed. RESULTS: Stratified data analysis revealed pronounced increases in
      reactivity to MCI/MI and MI in females, face dermatitis patients, and patients
      tested because of suspected cosmetic intolerance. The proportion of MI-positive
      patients among those reacting to MCI/MI increased from 43% to 59% between 2009
      and 2011. CONCLUSION: More widespread consumer exposure has most likely led to
      the increase in primary sensitization to MI and subsequently to a rise in MCI/MI
      reactions resulting from immunological cross-reactions. A reduction in the
      maximum use concentration of MI seems advisable. MI should be patch tested in the
      baseline series.

PMID- 22994270
TI  - Comparison of two-dimensional fast Raman imaging versus point-by-point
      acquisition mode for human bone characterization.
AB  - Recent technical developments gave rise to a new technology for two-dimensional
      fast Raman imaging: the DuoScan averaging mode (DS-Avg). This technology allows
      the acquisition of a Raman spectrum over a rastered macro spot. The aim of this
      study was to evaluate the interest of the DS-Avg applied on trabecular human
      bone. The evaluation was based on the comparison of the DS-Avg versus the point
      by-point mapping mode in real usage conditions. The signal-to-noise ratio, the
      spectral difference, and the physicochemical parameters were estimated for
      comparison of the efficiency of both modes. Principal component analysis was
      performed to explore the capacity of both modes to detect compositional
      variations. Results showed that the DS-Avg spectrum was equivalent to the average
      spectrum of individual spectra acquired with the point-by-point mode for the same
      sample area. The physicochemical parameters can be also determined from DS-Avg
      acquisition. The DS-Avg combined with an objective *50 allows a drastic decrease
      of the acquisition time, but the information about the micrometric composition is
      lost. The combination of the DS-Avg with an objective *100 is a good compromise
      between acquisition time and resolution. The DS-Avg is a useful technology for
      imaging mineral and organic phases of bones and for assessing their spatial
      distribution on large samples. The point-by-point imaging mode is more
      appropriate to assess the heterogeneous composition of bone within the micrometer
      scale. For the first time, this study compares the DuoScan averaging mode to the
      point-by-point imaging mode on a trabecular human bone.

PMID- 22994271
TI  - The identification of a spontaneous 47, XX, +21/46, XY chimeric fetus with male
      genitalia.
AB  - BACKGROUND: Approximately 30 sex-chromosome discordant chimera cases have been
      reported to date, of which only four cases carried trisomy 21. Here, we present
      an additional case, an aborted fetus with a karyotype of 47,XX, +21/46,XY. CASE
      PRESENTATION: Autopsy demonstrated that this fetus was normally developed and had
      male genitalia. Major characteristics of Down syndrome were not observed except
      an enlarged gap between the first and second toes. Karyotyping of tissues
      cultured from the fetus revealed the same chimeric chromosomal composition
      detected in the amniotic fluid but with a different ratio of [47,XX,+21] to
      [46,XY]. Further short tandem repeat analysis indicated a double paternal
      contribution and single maternal contribution to the fetus, with the additional
      chromosome 21 in the [47,XX,+21] cell lineage originating from the paternal side.
      CONCLUSION: We thus propose that this chimeric fetus was formed via the dispermic
      fertilization of a parthenogenetic ovum with one (Y) sperm and one (X,+21) sperm.

PMID- 22994272
TI  - Structural study of hydrated/dehydrated manganese thiophene-2,5-diphosphonate
      metal organic frameworks, Mn2(O3P-C4H2S-PO3).2H2O.
AB  - Synthesis of thiophene-2,5-diphosphonic acid 2 is reported, and its use for
      synthesis of the original pristine materials Mn(2)(O(3)P-C(4)H(2)S-PO(3)).2H(2)O
      3 is reported. The structure of material 3 has been fully resolved from single
      crystal X-ray diffraction. Mn(2)(O(3)P-C(4)H(2)S-PO(3)).2H(2)O 3 crystallizes in
      a monoclinic cell (space group P2) with the following parameters: a = 11.60(1) A,
      b = 4.943(5) A, c = 19.614(13) A, beta = 107.22 degrees . A noticeable feature of
      the structure of compound 3 is the orientation of the thiophene heterocycles that
      adopt two different orientations in two successive layers (along c). Thermal
      analysis of compound 3 indicates that the water molecules are easily removed from
      160 to 230  degrees C while the dehydrated structure is stable up to 500  degrees
      C. The dehydrated compound obtained from 3 can be rehydrated to give the
      polymorphic compound Mn(2)(O(3)P-C(4)H(2)S-PO(3)).2H(2)O 4, which crystallizes in
      an orthorhombic cell (space group Pnam) with the following parameters: a =
      7.5359(3) A, b = 7.5524(3) A, c = 18.3050(9) A. The main difference between the
      structures of 3 and 4 arises from both the orientation of the thiophene rings
      (herringbone-type organization in 4) and the structure of the inorganic layers.
      The thiophene-2,5-diphosphonic acid moieties engaged in materials 3 and 4 adopt a
      different orientation likely due to rotation around the P-C bonds and via the
      dehydrated state 5, which is likely more flexible than the hydrated states. Study
      of the magnetic properties performed on compound 3 and 4 and on the dehydrated
      compounds Mn(2)(O(3)P-C(4)H(2)S-PO(3)) 5 complemented by the structural study has
      permitted us to characterize the antiferromagnetic ground state of sample 3, a
      weak ferromagnetic component in sample 4, and complete paramagnetic behavior in
      sample 5.

PMID- 22994273
TI  - Structural and electronic characterization of nanocrystalline diamondlike carbon
      thin films.
AB  - The origin of low threshold field-emission (threshold field 1.25 V/MUm) in
      nanocrystalline diamond-like carbon (nc-DLC) thin films is examined. The
      introduction of nitrogen and thermal annealing are both observed to change the
      threshold field and these changes are correlated with changes to the film
      microstructure. A range of different techniques including micro-Raman and
      infrared spectroscopy, X-ray diffraction, electron microscopy, energy-dispersive
      X-ray analysis and time-of-flight-secondary ion mass spectroscopy are used to
      examine the properties of the films. A comparison of the field emission
      properties of nc-DLC films with atomically smooth amorphous DLC (a-DLC) films
      reveals that nc-DLC films have lower threshold fields. Our results show that nc
      DLC can be a good candidate for large area field emission display panels and cold
      cathode emission devices.

PMID- 22994274
TI  - Strengthening public health and primary care collaboration through electronic
      health records.
AB  - Electronic health records (EHRs) have great potential to serve as a catalyst for
      more effective coordination between public health departments and primary care
      providers (PCP) in maintaining healthy communities.  As a system for documenting
      patient health data, EHRs can be harnessed to improve public health surveillance
      for communicable and chronic illnesses. EHRs facilitate clinical alerts informed
      by public health goals that guide primary care physicians in real time in their
      diagnosis and treatment of patients.  As health departments reassess their public
      health agendas, the use of EHRs to facilitate this agenda in primary care
      settings should be considered. PCPs and EHR vendors, in turn, will need to
      configure their EHR systems and practice workflows to align with public health
      priorities as these agendas include increased involvement of primary care
      providers in addressing public health concerns.

PMID- 22994275
TI  - Health and wellness across the life span.

PMID- 22994276
TI  - Evolving from wireless terminals to mobile card readers at farmers' markets.

PMID- 22994277
TI  - No spot solutions: vitamin A supplementation in India.

PMID- 22994278
TI  - Current tobacco use among adults in the United States: findings from the National
      Adult Tobacco Survey.
AB  - OBJECTIVES: We assessed the prevalence and sociodemographic correlates of tobacco
      use among US adults. METHODS: We used data from the 2009-2010 National Adult
      Tobacco Survey, a national landline and cell phone survey of adults aged 18 years
      and older, to estimate current use of any tobacco; cigarettes; cigars,
      cigarillos, or small cigars; chewing tobacco, snuff, or dip; water pipes; snus;
      and pipes. We stratified estimates by gender, age, race/ethnicity, education,
      income, sexual orientation, and US state. RESULTS: National prevalence of current
      use was 25.2% for any tobacco; 19.5% for cigarettes; 6.6% for cigars, cigarillos,
      or small cigars; 3.4% for chewing tobacco, snuff, or dip; 1.5% for water pipes;
      1.4% for snus; and 1.1% for pipes. Tobacco use was greatest among respondents who
      were male, younger, of non-Hispanic "other" race/ethnicity, less educated, less
      wealthy, and lesbian, gay, bisexual, or transgender. Prevalence ranged from 14.1%
      (Utah) to 37.4% (Kentucky). CONCLUSIONS: Tobacco use varies by geography and
      sociodemographic factors, but remains prevalent among US adults. Evidence-based
      prevention strategies are needed to decrease tobacco use and the health and
      economic burden of tobacco-related diseases.

PMID- 22994279
TI  - Personal data and the public health paradigm.

PMID- 22994280
TI  - With the best intentions: lead research and the challenge to public health.
AB  - In 2001, Maryland's court of appeals was asked to decide whether researchers at
      Johns Hopkins University had engaged in unethical research on children. During
      the 1990s, Johns Hopkins's Kennedy Krieger Institute had studied 108 African
      American children, aged 6 months to 6 years, to find an inexpensive and
      "practical" means to ameliorate lead poisoning. We have outlined the arguments in
      the case and the conundrum faced by public health researchers as they confront
      new threats to our health from environmental and industrial insults. We examined
      the case in light of contemporary public health ideology, which prioritizes harm
      reduction over the historical goals of prevention. As new synthetic toxins-such
      as bisphenyl A, polychlorinated biphenyls, other chlorinated hydrocarbons,
      tobacco, vinyl, and asbestos-are discovered to be biologically disruptive and
      disease producing at low levels, lead provides a window into the troubling
      dilemmas public health will have to confront in the future.

PMID- 22994283
TI  - Adopting an active lifestyle during adulthood and health-related quality of life:
      the Doetinchem Cohort Study.
AB  - OBJECTIVES: We examined health-related quality of life in adults who became
      physically active at recommended levels over a 10-year period compared with
      adults with different physical activity patterns. Methods. We examined men and
      women aged 26 to 70 years (mean [SD] = 47.4 [10.1]) in the Doetinchem Cohort
      Study 3 times between 1995 and 2009. We distinguished participants who became
      physically active (n = 618), remained active (n = 1286), remained inactive (n =
      727), became physically inactive (n = 535), or with varying activity levels (n =
      455) over 10 years. We used multivariable linear regression analyses to determine
      differences in health-related quality of life (survey similar to the 36-Item
      Short-Form Health Survey) at 10-year follow-up. Results. Adults who became
      physically active reported better physical functioning, vitality, and general
      health after 10 years than did persistently inactive adults and adults who became
      inactive. They also reported less bodily pain and better social functioning than
      adults who became inactive. No differences were observed with adults who remained
      active or with varying activity levels. Conclusions. Adopting a physically active
      lifestyle may result in a better health-related quality of life, comparable to
      remaining physically active over 10 years.

PMID- 22994284
TI  - Better health requires partnerships and a systems approach.

PMID- 22994287
TI  - Reactions of group 3 metals with OF2: infrared spectroscopic and theoretical
      investigations of the group 3 oxydifluoride OMF2 and oxyfluoride OMF molecules.
AB  - The oxidifluoride molecules, OYF(2) and OLaF(2), are produced via the reactions
      of laser ablated metal atoms with OF(2) in solid argon. The product structures
      are characterized using matrix isolation infrared spectroscopy as well as
      theoretical calculations. Similar to the very recently characterized OScF(2)
      molecule, OYF(2) is predicted to have a (2)B(2) ground state with C(2v) symmetry
      while the heavier OLaF(2) has a (2)A" ground state with near C(2v) symmetry. The
      unpaired electron is mainly located on the terminal oxygen atom, suggesting
      radical character for the group 3 OMF(2) molecules. In addition, the closed shell
      singlet OMF molecules with bent geometries are also observed, and they are found
      to have triple metal-oxygen bonds with higher stretching frequencies and shorter
      bond lengths than their OMF(2) counterparts. alpha-Fluorine transfer from OF(2)
      to metal centers is predicted to be highly exothermic, which is very favorable
      for the formation of new OMF(2) and OMF species.

PMID- 22994286
TI  - Conceptual representations of perceptual knowledge.
AB  - Many neuroimaging studies of semantic memory have argued that knowledge of an
      object's perceptual properties are represented in a modality-specific manner.
      These studies often base their argument on finding activation in the left
      hemisphere fusiform gyrus-a region assumed to be involved in perceptual
      processing-when the participant is verifying verbal statements about objects and
      properties. In this paper, we report an extension of one of these influential
      papers-Kan, Barsalou, Solomon, Minor, and Thompson-Schill (2003 )-and present
      evidence for an amodal component in the representation and processing of
      perceptual knowledge. Participants were required to verify object-property
      statements (e.g., "cat-whiskers?"; "bear-wings?") while they were being scanned
      by functional magnetic resonance imaging (fMRI). We replicated Kan et al.'s
      activation in the left fusiform gyrus, but also found activation in regions of
      left inferior frontal gyrus (IFG) and middle-temporal gyrus, areas known to
      reflect amodal processes or representations. Further, only activations in the
      left IFG, an amodal area, were correlated with measures of behavioural
      performance.

PMID- 22994288
TI  - Amazon forest carbon dynamics predicted by profiles of canopy leaf area and light
      environment.
AB  - Tropical forest structural variation across heterogeneous landscapes may control
      above-ground carbon dynamics. We tested the hypothesis that canopy structure
      (leaf area and light availability) - remotely estimated from LiDAR - control
      variation in above-ground coarse wood production (biomass growth). Using a
      statistical model, these factors predicted biomass growth across tree size
      classes in forest near Manaus, Brazil. The same statistical model, with no
      parameterisation change but driven by different observed canopy structure,
      predicted the higher productivity of a site 500 km east. Gap fraction and a
      metric of vegetation vertical extent and evenness also predicted biomass gains
      and losses for one-hectare plots. Despite significant site differences in canopy
      structure and carbon dynamics, the relation between biomass growth and light fell
      on a unifying curve. This supported our hypothesis, suggesting that knowledge of
      canopy structure can explain variation in biomass growth over tropical landscapes
      and improve understanding of ecosystem function.

PMID- 22994290
TI  - Tertiary amine-triggered cascade S(N)2/cycloaddition: an efficient construction
      of complex azaheterocycles under mild conditions.
AB  - In this paper, an amine-triggered cascade S(N)2/cycloaddtion sequence between 2
      (acetoxymethyl)buta-2,3-dienoate 1 and various pi-system functionalized
      tosylamides 3 has been reported, which provides a facile method for
      stereoselective construction of structurally diverse azaheterocycles.

PMID- 22994289
TI  - Structure, mechanism and regulation of an artificial microbial ecosystem for
      vitamin C production.
AB  - At present, the modern two-step fermentation process is one of the major
      approaches for the industrial production of vitamin C. The key step in this
      process is the conversion of L-sorbose to 2-keto-L-gulonic acid (2-KLG), the
      vitamin C precursor, which is accomplished by an artificial microbial ecosystem
      consisting of Ketogulonicigenium vulgare and Bacillus megaterium. This review
      describes current progress in understanding this ecosystem, not only the
      individual physiological characteristics of the two strains, but also the
      interactions between them. Special emphasis is placed on recent systems biology
      studies of the ecosystem. We also discuss the regulation and improvement of this
      ecosystem, including analysis of the fermentation medium components and genetic
      engineering and optimum fermentative strategies. Finally, perspectives on the
      knowledge and engineering of this important artificial microbial ecosystem are
      discussed. 

PMID- 22994292
TI  - High-volume hemofiltration reduces the expression of myocardial tumor necrosis
      factor-alpha in septic shock pigs.
AB  - Increasing evidence indicates that the expression of tumor necrosis factor-alpha
      (TNF-alpha) in myocardium correlates with the severity of cardiac dysfunction in
      septic shock. The aim of this study was to investigate the impact of high-volume
      hemofiltration (HVHF) on the expression of TNF-alpha in myocardium in septic
      shock pigs. Sixteen male Landrace pigs weighing 31 +/- 5 kg were randomly
      assigned to control group (n = 4), septic shock group (n = 6), and HVHF group
      (septic shock + HVHF, n = 6). All animals were anesthetized and mechanically
      ventilated. After baseline examinations, septic shock group and HVHF group
      underwent induction of peritonitis. One hour later, the animals in HVHF group
      received treatment with HVHF and the treatment was continued for 12 h. As the
      control of HVHF group, the animals in septic shock group received the same
      support but hemofiltration. Twelve hours after HVHF therapy, all the animals were
      sacrificed. TNF-alpha and nitric oxide (NO) levels in both circulation and
      myocardium were measured. Compared with those of septic shock animals, the levels
      of cardiac output, stroke volume, and mean arterial pressure were better
      maintained in HVHF group. The expression of TNF-alpha in myocardium in HVHF group
      was lower than that in septic shock group (44.17 +/- 18.70 vs. 92.50 +/- 33.89
      pg/mg protein, P = 0.015). The difference of TNF-alpha in circulation between
      HVHF group and septic shock group was no significance at different time. However,
      circulating NO in HVHF group was lower than that in septic shock group. These
      results suggest that HVHF improves hemodynamics and heart dysfunction in septic
      shock pigs, which may be attributed to reduction of TNF-alpha in myocardium but
      not in circulation.

PMID- 22994293
TI  - Effectiveness of an intervention on uptake of maternal care in four counties in
      Ningxia, China.
AB  - OBJECTIVES: To understand the utilisation of prenatal care and hospitalised
      delivery among pregnant Muslim women in Ningxia, China, and to explore the
      effectiveness of the integrated interventions to reduce maternal mortality.
      METHODS: Cross-sectional surveys before and after the intervention were carried
      out. Using multistage sampling, 1215 mothers of children <5 years old were
      recruited: 583 in the pre-intervention survey and 632 in the post-intervention
      study. Data on prenatal care and delivery were collected from face-to-face
      interviews. Maternal mortality ratio (MMR) data were obtained from the local
      Maternal and Child Mortality Report System. RESULTS: After the intervention, the
      MMR significantly decreased (45.5 deaths per 100,000 live births to 32.7 deaths).
      Fewer children were born at home after the intervention than before the
      intervention (OR, 0.11; 95% CI, 0.08-0.15). The proportion of women who attended
      prenatal care at least once increased from 78.2% to 98.9% (OR, 24.55; 95% CI,
      11.37-53.12). The proportion of women who had prenatal visit(s) in the first
      trimester of pregnancy increased from 35.1% to 82.6% (OR, 8.77; 95% CI, 6.58
      11.69). The quality of prenatal care was greatly improved. Effects of the
      intervention on the utilisation of maternal care remained significant after
      adjusting for education level and household possessions. CONCLUSIONS: The
      findings suggest that integrated strategies can effectively reduce maternal
      mortality.

PMID- 22994294
TI  - Structure and properties of aqueous methylcellulose gels by small-angle neutron
      scattering.
AB  - Cold, semidilute, aqueous solutions of methylcellulose (MC) are known to undergo
      thermoreversible gelation when warmed. This study focuses on two MC materials
      with much different gelation performance (gel temperature and hot gel modulus)
      even though they have similar metrics of their coarse-grained chemical structure
      (degree-of-methylether substitution and molecular weight distribution). Small
      angle neutron scattering (SANS) experiments were conducted to probe the structure
      of the aqueous MC materials at pre- and postgel temperatures. One material (MC1,
      higher gel temperature) exhibited a single almost temperature-insensitive gel
      characteristic length scale (zeta(c) = 1090 +/- 50 A) at postgelation
      temperatures. This length scale is thought to be the gel blob size between
      network junctions. It also coincides with the length scale between entanglement
      sites measured with rheology studies at pregel temperatures. The other material
      (MC2, lower gel temperature) exhibited two distinct length scales at all
      temperatures. The larger length scale decreased as temperature increased. Its
      value (zeta(c1) = 1046 +/- 19 A) at the lowest pregel temperature was
      indistinguishable from that measured for MC1, and reached a limiting value
      (zeta(c1) = 450 +/- 19 A) at high temperature. The smaller length scale (zeta(c2)
      = 120 to 240 A) increased slightly as temperature increased, but remained on the
      order of the chain persistence length (130 A) measured at pregel temperatures.
      The smaller blob size (zeta(c1)) of MC2 suggests a higher bond energy or a
      stiffer connectivity between network junctions. Moreover, the number density of
      these blobs, at the same reduced temperature with respect to the gel temperature,
      is orders of magnitude higher for the MC2 gels. Presumably, the smaller gel
      length scale and higher number density lead to higher hot gel modulus for the low
      gel temperature material.

PMID- 22994295
TI  - Controlling newly diagnosed type 2 diabetes mellitus with metformin managed pain
      symptoms in a patient affected with Dercum's disease.

PMID- 22994296
TI  - Segmentation algorithms for ear image data towards biomechanical studies.
AB  - In recent years, the segmentation, i.e. the identification, of ear structures in
      video-otoscopy, computerised tomography (CT) and magnetic resonance (MR) image
      data, has gained significant importance in the medical imaging area, particularly
      those in CT and MR imaging. Segmentation is the fundamental step of any automated
      technique for supporting the medical diagnosis and, in particular, in
      biomechanics studies, for building realistic geometric models of ear structures.
      In this paper, a review of the algorithms used in ear segmentation is presented.
      The review includes an introduction to the usually biomechanical modelling
      approaches and also to the common imaging modalities. Afterwards, several
      segmentation algorithms for ear image data are described, and their specificities
      and difficulties as well as their advantages and disadvantages are identified and
      analysed using experimental examples. Finally, the conclusions are presented as
      well as a discussion about possible trends for future research concerning the ear
      segmentation. 

PMID- 22994297
TI  - Pleistocene survival on central Alpine nunataks: genetic evidence from the
      jumping bristletail Machilis pallida.
AB  - Mechanisms of survival during the Pleistocene glaciation periods have been
      studied for more than a century. Until now, molecular studies that confirmed
      animal survival on Alpine nunataks, that is, ice-free summits surrounded by
      glaciers, were restricted to peripheral areas. Here, we search for molecular
      signatures of inner-Alpine survival of the narrow endemic and putatively
      parthenogenetic Alpine jumping bristletail Machilis pallida combining
      mitochondrial and AFLP data from its three known populations. The mitochondrial
      data indicate survival on both peripheral and central nunataks, the latter
      suggesting that refugia in the centre of the Alpine main ridge were more
      widespread than previously recognized. Incongruences between mitochondrial and
      AFLP patterns suggest a complex evolutionary history of the species and may be
      explained via parallel fixation of parthenogenesis of different origins during
      the last glacial maximum. We suggest that the inferred parthenogenesis may have
      been essential for central nunatak survival, but may pose a serious threat for M.
      pallida in consideration of the present climatic changes.

PMID- 22994298
TI  - Long-term vagus nerve stimulation in children with focal epilepsy.
AB  - OBJECTIVES: The aim of the study was to evaluate the long-term efficacy and
      hospitalization rates in children with refractory focal epilepsy treated by vagus
      nerve stimulation. MATERIALS AND METHODS: We retrospectively analyzed 15 children
      with intractable focal epilepsy treated by vagus nerve stimulation (mean age of
      14.6 +/- 2.5 years at the time of implantation). We analyzed the treatment
      effectiveness at 1, 2, and 5 year follow-up visits. We counted the average number
      of urgent hospitalizations and number of days of urgent hospitalization per year
      for each patient before and after the VNS implantation. RESULTS: The mean seizure
      reduction was 42.5% at 1 year, 54.9% at 2 years, and 58.3% at 5 years. The number
      of responders was 7 (46.7%) at 1 year and 9 (60%) at both 2 and 5 years. The mean
      number of urgent hospitalizations per patient was 1.0 +/- 0.6 per year
      preoperatively and 0.3 +/- 0.5 per year post-operatively (P < 0.0001). The mean
      number of days of urgent hospitalization per patient was 9.3 +/- 6.1 per year
      preoperatively and 1.3 +/- 1.8 per year post-operatively ( < 0.0001).
      CONCLUSIONS: Vagus nerve stimulation is an effective method of treating children
      with refractory focal epilepsy. It leads to a substantial decrease in the number
      and duration of urgent hospitalizations.

PMID- 22994299
TI  - Different critical perinatal periods and hypothalamic sites of oestradiol action
      in the defeminisation of luteinising hormone surge and lordosis capacity in the
      rat.
AB  - Female rats show a gonadotrophin-releasing hormone (GnRH)/luteinising hormone
      (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do
      not because of brain defeminisation during the developmental period by perinatal
      oestrogen converted from androgen. The present study aimed to identify the
      site(s) of oestrogen action and the critical period for defeminising the
      mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such
      as steroidal manipulations, brain local implantation of oestradiol (E(2) ) or
      administration of an NMDA antagonist, were examined for their ability to show an
      E(2) -induced LH surge at adulthood. Lordosis behaviour was examined to compare
      the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c.
      oestradiol-benzoate administration on either the day before birth (E21), the day
      of birth (D0) or day 5 (D5) postpartum completely abolished the E(2) -induced LH
      surge at adulthood in female rats, although the same treatment did not inhibit
      lordosis. Perinatal castration on E21 or D0 partially rescued the E2-induced LH
      surge in genetically male rats, whereas castration from E21 to D5 totally rescued
      lordosis. Neonatal E(2)  implantation in the anterior hypothalamus including the
      anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the
      E(2) -induced LH surge in female rats, whereas E(2)  implantation in the mid and
      posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis
      was not affected by neonatal E(2)  implantation in any hypothalamic regions. In
      male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH
      surge. Taken together, these results suggest that an anterior hypothalamic region
      such as the AVPV/POA region is a perinatal site of oestrogen action where the
      GnRH/LH regulating system is defeminised to abolish the oestrogen-induced surge.
      The mechanism for defeminisation of the GnRH/LH surge system might be different
      from that of sexual behaviour, in terms of the site(s) of oestrogen action and
      critical period, as well as the neurotransmitter system involved.

PMID- 22994301
TI  - Two-dimensional peptide separation improving sensitivity of selected reaction
      monitoring-based quantitative proteomics in mouse liver tissue: comparing off-gel
      electrophoresis and strong cation exchange chromatography.
AB  - Protein expression analysis is one of the most powerful tools to further the
      understanding of biological systems. Progress in the field of mass spectrometry
      has shifted focus from gel-based approaches to the upcoming LC-selected reaction
      monitoring (SRM) technique which combines high technical accuracy with absolute
      quantification of proteins and the capability for high-throughput analyses. Due
      to these properties, LC-SRM has the potential to become the foundation for
      biomarker analysis, targeted hypothesis driven proteomic studies and contribute
      to the field of systems biology. While the performance of LC-SRM applied to
      samples from various bodily fluids, particularly plasma, and microorganisms has
      been extensively investigated, there is only little experience with its
      application to animal tissue samples. Here, we show that a conventional one
      dimensional LC-SRM workflow applied to mouse liver tissue suffers from a
      shortcoming in terms of sensitivity for lower abundance proteins. This problem
      could be solved through the extension of the standard workflow by an additional
      dimension of separation at the peptide level prior to online LC-SRM. For this
      purpose, we used off-gel electrophoresis (OGE) which is also shown to outperform
      strong cation exchange (SCX) in terms of resolution, gain of signal intensity,
      and predictability of separation. The extension of the SRM workflow by a high
      resolving peptide separation technique is an ideal combination as it allows the
      addition of stable isotope standards directly after trytic digestion and will
      increase the dynamic range of protein abundances amenable by SRM in animal
      tissue.

PMID- 22994302
TI  - Central nervous system marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue type involving the brain and spinal cord parenchyma.
AB  - We present a case of a 53-year-old HIV negative man with a 2-month history of
      progressive recent memory disturbance, gait disturbance and urinary incontinence.
      On MRI, an infiltrative tumor in the brain and spinal cord was noted. Subsequent
      positron emission tomography studies along with bone marrow biopsy and serum
      protein electrophoresis showed no evidence of systemic disease. Open brain biopsy
      results revealed a small lymphocytic infiltrate with scattered plasma cells in a
      predominantly perivascular growth pattern. The morphology was consistent with
      involvement by a low-grade B-cell lymphoma. Immunohistochemical findings showed
      CD20+, CD10-, CD5-, TdT-, EBV-encoded RNA in situ- and IgM-. The above findings
      were consistent with involvement by a non-dural extranodal marginal zone B-cell
      lymphoma (MZBCL) primary to the brain and spinal cord. This is a case report of a
      CNS MZBCL of mucosa-associated lymphoid tissue type involving the brain and
      spinal cord parenchyma.

PMID- 22994300
TI  - Lipid-based vectors for siRNA delivery.
AB  - siRNA therapeutics has developed rapidly and already there are clinical trials
      ongoing or planned; however, the delivery of siRNA into cells, tissues or organs
      remains to be a major obstacle. Lipid-based vectors hold the most promising
      position among non-viral vectors, as they have a similar structure to cell or
      organelle membranes. But when used in the form of liposomes, these vectors have
      shown some problems. Therefore, either the nature of lipids themselves or forms
      used should be improved. As a novel class of lipid like materials, lipidoids have
      the advantages of easy synthesis and the ability for delivering siRNA to obtain
      excellent silencing activity. However, the toxicities of lipidoids have not been
      thoroughly studied. pH responsive lipids have also gained great attention
      recently, though some of the amine-based lipids are not novel in terms of
      chemical structures. More complex self-assembly structures, such as LPD (LPH) and
      LCP, may provide a good solution to siRNA delivery. They have demonstrated
      controlled particle morphology and size and siRNA delivery activity for both in
      vitro and in vivo.

PMID- 22994303
TI  - Encephalopathy with amyloid angiopathy and numerous amyloid plaques with low
      levels of CSF Abeta1-40/Abeta1-42.
AB  - A middle-aged male suffering from encephalopathy with cerebral amyloid angiopathy
      (CAA) with amyloid beta (Abeta) presented with initial symptoms of transient
      consciousness disturbance and left visual field photophobia. Lesions with
      aberrantly high signal on T2-weighted magnetic resonance imaging (MRI) of the
      brain appeared in the right temporal lobe posterior to the occipital lobe and
      spread to other areas. Brain biopsy revealed Abeta deposits in vascular walls and
      numerous diffuse plaques in parenchymal areas. Based on MRI findings, Initial
      corticosteroid therapy with beta methasone effectively improved the neurological
      symptoms of consciousness disturbance and motor deficits. After corticosteroid
      therapy was stopped at 4 weeks, recurrence occurred. Additional corticosteroids
      did not improve clinical symptoms and the patient progressed to a bed-ridden
      state with a severe consciousness disturbance. Notably, CSF Abeta1-42 and CSF
      Abeta1-40 decreased while the recurrent encephalopathy worsened. After intense
      deterioration, the patient became stable. CSF Abeta1-42 increased but remained at
      a very low level. This case of CAA encephalopathy with apolipoprotein E
      epsilon4/epsilon4 homozygosity showed Abeta deposits in vascular walls and
      numerous diffuse plaques in parenchymal areas. The clinical course suggests that
      reduction of CSF Abeta1-42 and Abeta1-40 might be related to clinical
      deterioration in cases of encephalopathy.

PMID- 22994304
TI  - Dermoscopy for the pediatric dermatologist, part ii: dermoscopy of genetic
      syndromes with cutaneous manifestations and pediatric vascular lesions.
AB  - Genetic syndromes including basal cell nevus syndrome (BSNS), xeroderma
      pigmentosum (XP), and epidermodysplasia verruciformis (EV) predispose the
      individual to skin cancer. Basal cell carcinomas (BCCs) often develop in patients
      with BCNS and XP. One of the aims of surveillance examination in these patients
      is to detect BCC while the tumors are still small and easy to manage. Dermoscopy,
      by allowing the visualization of arborizing vessels, ovoid nests, nonaggregated
      blue-gray globules, and spoke-wheel and leaf-like structures, can facilitate in
      the early detection of BCC. Patients with XP are also at risk for developing
      squamous cell carcinoma (SCC). Dermoscopy can assist in the early detection of
      these cancers by allowing the observer to visualize focal glomerular vessels,
      which is a common feature seen in SCC. This feature can also assist in detecting
      SCC developing in other syndromes such as EV and epidermolysis bullosa (EB). In
      addition to helping in the detection of BCC and SCC, dermoscopy can also help
      detect melanoma in individuals with XP and evaluate nevi developing in those with
      EB. This review will discuss how dermoscopy can be used in the management of
      patients with BSNS, XP, EV, and EB and will discuss the dermoscopic findings of
      vascular lesions, including pyogenic granuloma, hemangioma, port-wine stain, and
      lymphangioma circumscriptum.

PMID- 22994305
TI  - Antidepressant use and gestational hypertension: does evidence support causality?

PMID- 22994307
TI  - Application of umbilical cord serum eyedrops after laser epithelial
      keratomileusis.
AB  - PURPOSE: To investigate the efficacy of umbilical cord serum eyedrops after laser
      epithelial keratomileusis (LASEK). METHODS: Sixty patients (120 eyes) with myopia
      who underwent LASEK were studied. Thirty-two patients (64 eyes) were treated with
      20% umbilical cord serum eyedrops in combination with conventional treatment
      (group A), and 28 patients (56 eyes) received conventional treatment only (group
      B). Epithelial healing time was analysed. Visual acuity, refraction, haze score
      (0-4) and tear film and ocular surface parameters were evaluated at 1, 2, 4 and
      12 weeks after LASEK. The concentration of transforming growth factor (TGF)-beta1
      in tears was measured with ELISA at 1 week after LASEK. RESULTS: No significant
      differences in visual acuity and refraction were found between groups. The mean
      time to epithelial healing was 3.53 +/- 1.19 days in group A and 3.91 +/- 1.41
      days in group B (p = 0.18). The mean haze scores at 2 and 4 weeks were 0.59 +/-
      0.80 and 0.31 +/- 0.54 in group A and 1.06 +/- 0.91 (p = 0.02) and 0.69 +/- 0.78
      (p = 0.03) in group B. Four and 12 weeks after LASEK, tear film break-up time was
      longer and keratoepitheliopathy score was lower in group A compared with group B.
      The mean concentration of TGF-beta1 was lower in group A compared with group B (p
      = 0.01). CONCLUSION: Application of 20% umbilical cord serum eyedrops in addition
      to conventional treatment after LASEK can reduce early postoperative corneal haze
      and improve tear film and ocular surface parameters.

PMID- 22994306
TI  - Neurogenic mucosal bicarbonate secretion in guinea pig duodenum.
AB  - BACKGROUND AND PURPOSE: To test a hypothesis that: (i) duodenal pH and osmolarity
      are individually controlled at constant set points by negative feedback control
      centred in the enteric nervous system (ENS); (ii) the purinergic P2Y(1) receptor
      subtype is expressed by non-cholinergic secretomotor/vasodilator neurons, which
      represent the final common excitatory pathway from the ENS to the bicarbonate
      secretory glands. EXPERIMENTAL APPROACH: Ussing chamber and pH-stat methods
      investigated involvement of the P2Y(1) receptor in neurogenic stimulation of
      mucosal bicarbonate (HCO(3)(-)) secretion in guinea pig duodenum. KEY RESULTS:
      ATP increased HCO(3)(-) secretion with an EC(50) of 160 nM. MRS2179, a selective
      P2Y(1) purinergic receptor antagonist, suppressed ATP-evoked HCO(3)(-) secretion
      by 47% and Cl(-) secretion by 63%. Enteric neuronal blockade by tetrodotoxin or
      exposure to a selective vasoactive intestinal peptide (VIP, VPAC(1)) receptor
      antagonist suppressed ATP-evoked HCO(3)(-) secretion by 61 and 41%, respectively,
      and Cl- by 97 and 70% respectively. Pretreatment with the muscarinic antagonist,
      scopolamine did not alter ATP-evoked HCO3(-) or Cl(-) secretion. CONCLUSION AND
      IMPLICATIONS: Whereas acid directly stimulates the mucosa to release ATP and
      stimulate HCO(3)(-) secretion in a cytoprotective manner, neurogenically evoked
      HCO(3)(-) secretion accounts for feedback control of optimal luminal pH for
      digestion. ATP stimulates duodenal HCO(3)(-) secretion through an excitatory
      action at purinergic P2Y(1) receptors on neurons in the submucosal division of
      the ENS. Stimulation of the VIPergic non-cholinergic secretomotor/vasodilator
      neurons, which are one of three classes of secretomotor neurons, accounts for
      most, if not all, of the neurogenic secretory response evoked by ATP.

PMID- 22994308
TI  - Triphenyl phosphite, a new allergen in polyvinylchloride gloves.
AB  - BACKGROUND: Contact allergy to polyvinylchloride (PVC) gloves has been reported
      relatively seldom. In spring 2011, 5 of our patients had patch test reactions to
      PVC gloves. We obtained a collection of PVC raw materials from industrial
      producers and suppliers of chemical compounds to be patch tested on patients with
      suspected PVC glove contact allergy. OBJECTIVES: To report the first results of
      these new test substances. METHODS: The patients were patch tested with the newly
      obtained test substances, plastics and glues series, and isocyanates and
      isocyanate prepolymers. We analysed nine PVC glove samples for triphenyl
      phosphate and its derivatives. RESULTS: Two patients reacted to a technical PVC
      antioxidant and one of its components, triphenyl phosphite (TPP). Contact allergy
      to TPP was very strong in 1 patient, and was the main cause of her hand
      dermatitis, whereas the other patient also had other contact allergies explaining
      her symptoms. Three patients reacted to their PVC gloves, but the specific
      allergen was not identified. Six PVC glove samples contained TPP at
      concentrations of 0.004-0.099%. TPP transforms into triphenyl phosphate during
      storage. CONCLUSIONS: TPP represents a new allergen in PVC gloves. It was
      detected in several PVC gloves in fairly high concentrations.

PMID- 22994309
TI  - A review of cognitive neuropsychiatry in the taxonomy of eating disorders: state,
      trait, or genetic?
AB  - A greater understanding of neuropsychological traits in eating disorders may help
      to construct a more biologically based taxonomy. The aim of this paper is to
      review the current evidence base of neuropsychological traits in people with
      eating disorders. Evidence of difficulties in set shifting, weak central
      coherence, emotional processing difficulties, and altered reward sensitivity is
      presented for people both in the acute and recovered phase of the illness. These
      traits are also seen in first degree relatives. At present there is limited
      research linking these neuropsychological traits with genetic and neuroanatomical
      measures. In addition to improving the taxonomy of eating disorders,
      neuropsychological traits may be of value in producing targeted treatments.

PMID- 22994310
TI  - The 16 CB11(CH3)n(CD3)(12-n)* radicals with 5-fold substitution symmetry: spin
      density distribution in CB11Me12(*).
AB  - The syntheses of all 16 CB(11)(CH(3))(n)(CD(3))(12-n)(*) radicals with 5-fold
      substitution symmetry are described. The variation in the width of their broad
      and featureless electron paramagnetic resonance signals as a function of the
      deuteriation pattern is used to deduce the relative values of the average
      hyperfine coupling constants a(H) of the hydrogen atoms in the ipso (1), ortho (2
      6), meta (7-11), and para (12) methyl groups, a(H)(i):a(H)(o):a(H)(m):a(H)(p) =
      (0.18 +/- 0.09):(0.71 +/- 0.02):(1.00 +/- 0.03):(0.52 +/- 0.05), and these can be
      compared with ratios expected from a B3LYP/EPRII calculation, 0.04:0.55:1:0.51.

PMID- 22994311
TI  - Fluorescence photoactivation by intermolecular proton transfer.
AB  - We designed a strategy to activate fluorescence under the influence of optical
      stimulations based on the intermolecular transfer of protons. Specifically, the
      illumination of a 2-nitrobenzyl derivative at an activating wavelength is
      accompanied by the release of hydrogen bromide. In turn, the photogenerated acid
      encourages the opening of an oxazine ring embedded within a halochromic compound.
      This structural transformation extends the conjugation of an adjacent coumarin
      fluorophore and enables its absorption at an appropriate excitation wavelength.
      Indeed, this bimolecular system offers the opportunity to activate fluorescence
      in liquid solutions, within rigid matrixes and inside micellar assemblies,
      relying on the interplay of activating and exciting beams. Furthermore, this
      strategy permits the permanent imprinting of fluorescent patterns on polymer
      films, the monitoring of proton diffusion within such materials in real time on a
      millisecond time scale, and the acquisition of images with spatial resolution at
      the nanometer level. Thus, our operating principles for fluorescence activation
      can eventually lead to the development of valuable photoswitchable probes for
      imaging applications and versatile mechanisms for the investigation of proton
      transport.

PMID- 22994312
TI  - Complete mitochondrial genome sequence of Cirrhinus mrigala (Hamilton, 1822).
AB  - The complete mitochondrial genome of Cirrhinus mrigala was determined using the
      polymerase chain reaction. The mitogenome (16,594 bp) has the typical vertebrate
      mitochondrial gene arrangement, including 13 protein-coding genes, 22 tRNA genes,
      two rRNA genes and one control region. The overall base composition on the heavy
      strand was as follows: A: 32.0%, G: 15.5%, C: 28.0%, T: 24.55% and the A+T
      content: 56.5%. The control region contains a dinucleotide repeat motif, (TA)14,
      a termination-associated sequence and three conserved sequence blocks. These
      mitogenome sequence data would play an important role in population genetics and
      the molecular taxonomy of cultivable cyprinids in India.

PMID- 22994313
TI  - Subtle mutations in the SMN1 gene in Chinese patients with SMA: p.Arg288Met
      mutation causing SMN1 transcript exclusion of exon7.
AB  - BACKGROUND: Proximal spinal muscular atrophy (SMA) is a common neuromuscular
      disorder resulting in death during childhood. Around 81~95% of SMA cases are a
      result of homozygous deletions of survival motor neuron gene 1 (SMN1) gene or
      gene conversions from SMN1 to SMN2. Less than 5% of cases showed rare subtle
      mutations in SMN1. Our aim was to identify subtle mutations in Chinese SMA
      patients carrying a single SMN1 copy. METHODS: We examined 14 patients from 13
      unrelated families. Multiplex ligation-dependent probe amplification analysis was
      carried out to determine the copy numbers of SMN1 and SMN2. Reverse transcription
      polymerase chain reaction (RT-PCR) and clone sequencing were used to detect
      subtle mutations in SMN1. SMN transcript levels were determined using
      quantitative RT-PCR. RESULTS: Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys,
      p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met) were identified in 12
      patients. The p.Tyr277Cys mutation has not been reported previously. The
      p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in
      Chinese SMA patients and the first two mutations seem to be the common ones.
      Levels of full length SMN1 (fl-SMN1) transcripts were very low in patients
      carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers.
      In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-SMN1 transcripts
      were reduced but not significant. The SMN1 transcript almost skipped exon 7
      entirely in patients with the p.Arg288Met mutation. CONCLUSIONS: Our study
      reveals a distinct spectrum of subtle mutations in SMN1 of Chinese SMA patients
      from that of other ethnicities. The p.Arg288Met missense mutation possibly
      influences the correct splicing of exon 7 in SMN1. Mutation analysis of the SMN1
      gene in Chinese patients may contribute to the identification of potential ethnic
      differences and enrich the SMN1 subtle mutation database.

PMID- 22994314
TI  - Dual environment-responsive polyplex carriers for enhanced intracellular delivery
      of plasmid DNA.
AB  - In this study, we describe a multifunctional, nontoxic delivery vehicle with dual
      environment sensitivity to deliver plasmid DNA (pDNA) into the cytoplasm of
      cells. This delivery vehicle was designed to be destabilized by reduction of
      disulfide cross-links in the intracellular environment and also to contain pH
      sensitive membrane-destabilizing activity in acidic late endosomal/lysosomal
      compartments to allow escape of pDNA into the cell cytoplasm. Polyion complex
      formation was used to form ternary polyplexes using ionic polymers containing
      specific chemistries to achieve functional demands. First, template binary
      polyplexes were formed by association of cationic poly(l-lysine) containing thiol
      groups (PLys(PDP)) with pDNA and were subsequently cross-linked by disulfide
      formation for increased stability. Then, binary cross-linked polyplexes were
      coated with a pH-sensitive membrane-active polyanion, poly(ethylene glycol)-b
      poly(aspartamide(DET-Aco)) (PEG-PAsp(DET-Aco)), to produce ternary cross-linked
      polyplexes. PEG-PAsp(DET-Aco) comprises two repeating units of aminoethylene in
      PAsp side chains and primary amines modified with anionic cis-aconitic groups.
      PEG-PAsp(DET-Aco) degrades at acidic pH to generate the parent PEG-PAsp(DET)
      polymer, which is active toward late endosomal/lysosomal membranes and thus can
      assist in the endosomal escape of pDNA following endocytosis. Binary/ternary
      cross-linked polyplexes remained stable toward counter polyanion exchange with
      dextran sulfate, but released pDNA following disulfide reduction. Ternary cross
      linked polyplexes formed by addition of PEG-PAsp(DET-Aco) resulted in enhanced
      gene transfection efficiency in cultured cells (Huh-7 and HUVEC) without
      associated cytotoxicity. The enhanced gene transfection was found to be
      correlated with improved endosomal escape by observation of intracellular
      trafficking using confocal laser scanning microscopy. This multifunctional
      ternary cross-linked polyplex demonstrates the successful design of a gene
      delivery vehicle utilizing intracellular stimuli, and is a promising platform for
      further development toward practical use.

PMID- 22994319
TI  - An empirical evaluation of proposed changes for gambling diagnosis in the DSM-5.
AB  - AIMS: Recommendations related to pathological gambling for the fifth edition of
      the Diagnostic and statistic manual for mental disorders (DSM) are to eliminate
      the criterion related to committing illegal acts and reduce the threshold for
      diagnosis from five to four criteria. This study evaluated the impact of these
      changes on prevalence rates and classification accuracy. DESIGN: Data were
      analyzed from five samples, varying in severity of gambling problems. SETTINGS
      AND PARTICIPANTS: Surveys of randomly selected household residents in the United
      States (US) (n = 2417), gambling patrons (n = 450), individuals in brief
      intervention studies (n = 375), patients in community-based gambling treatment
      programs (n = 149) and participants in randomized intervention studies (n = 319).
      MEASUREMENTS: The national opinion research center DSM-IV screen for gambling
      problems (NODS) was administered to all participants. Internal consistency and
      factor structure were evaluated using both 10 and nine criteria. Base rates, hit
      rates, sensitivity, specificity and overall agreement were compared across
      classification systems, using DSM-IV classification as the standard. FINDINGS:
      Eliminating the illegal acts criterion did not impact internal consistency and
      modestly improved variance accounted for in the factor structure. In comparing a
      classification system using four of 10 criteria versus one using four of nine,
      the four of nine system yielded equal or slightly better classification accuracy
      in all comparisons and across all samples. CONCLUSIONS: The inclusion of the
      illegal acts criterion in the proposed DSM-V pathological gambling diagnosis does
      not appear necessary for diagnosis of pathological gambling and, if it is
      eliminated, reducing the cut-point to four results in more consistent diagnoses
      relative to the current classification system.

PMID- 22994320
TI  - Classification of cesarean sections among immigrants in Belgium.
AB  - OBJECTIVE: To provide insight into the differential effect of immigration on
      cesarean section (CS) rates, using the Robson classification. DESIGN: A
      population-based study using birth certificates from the birth registry of 2009.
      SETTING: All births in two of the three Belgian regions excluding Flanders.
      POPULATION: 37 628 deliveries from Belgian and immigrant mothers from sub-Saharan
      Africa, Maghreb and Eastern Europe. METHODS: Multivariate analyses using CS as
      the dependent variable and immigration status as the primary independent
      variable. Several multivariate logistic regression models were built including
      medical, anthropometric, socio-economic characteristics, and medical
      interventions. The impact of analyzing all delivery sites together was tested
      using mixed-effect analyses. MAIN OUTCOME MEASURES: CSs of immigrant subgroups
      compared with Belgian women. RESULTS: CS rates varied according to immigrant
      subgroups. Mothers from sub-Saharan Africa had an adjusted odds ratio of 2.06
      (1.62-2.63) for CS compared with Belgian natives. Increased risk for mothers from
      sub-Saharan Africa compared with Belgian natives was found among nulliparous and
      multiparous women without previous CS, and a term, singleton fetus in cephalic
      position. In comparison, nulliparous East European mothers with a term singleton
      fetus in cephalic position in spontaneous labor had an adjusted odds ratio of
      0.29 (0.08-0.99) for CS. CONCLUSIONS: CS rates currently vary between Robson
      categories in immigrant subgroups. Immigrant mothers from sub-Saharan Africa with
      a term, singleton infant in cephalic position, without previous CS, appear to
      carry the highest burden.

PMID- 22994321
TI  - 20-Residue and 11-residue peptaibols from the fungus Trichoderma longibrachiatum
      are synergistic in forming Na+/K+ -permeable channels and adverse action towards
      mammalian cells.
AB  - Certain species of the filamentous fungal genus Trichoderma (e.g. Trichoderma
      longibrachiatum and Trichoderma citrinoviride) are among the emerging clinical
      pathogens and also the most common species in the indoor space of mould-damaged
      buildings. The molecules involved in its pathology are not known. In the present
      study, we report that 0.5-2.6 wt% of the T. longibrachiatum mycelial biomass
      consisted of thermostable secondary metabolites mitochondriotoxic to mammalian
      cells. These were identified by LC/MS as one 11-residue and eight 20-residue
      peptaibols, AcAib-Asn-Leu/Ile-Leu/Ile-Aib-Pro-Leu/Ile-Leu/Ile-Aib-Pro-Leuol/Ileol
      (1175 Da) and AcAib-Ala-Aib-Ala-Aib-Ala/Aib-Gln-Aib-Val/Iva-Aib-Gly-Leu/Ile-Aib
      Pro-Val/Iva-Aib-Val/Iva/Aib-Gln/Glu-Gln-Pheol(1936-1965 Da) (Aib, alpha
      aminoisobutyric acid; Ac, acetyl; Ileol, isoleucinol; Iva, isovaline; Leuol,
      leucinol; Pheol, phenylalaninol). The toxic effects on boar sperm cells depended
      on these peptaibols, named trilongins. The trilongins formed voltage dependent,
      Na(+)/K(+) permeable channels in biomembranes. The permeability ratios for Na(+)
      ions, relative to K(+), of the 11-residue trilongin channel (0.95 : 1) and the 20
      residue trilongin channel (0.8 : 1) were higher than those of alamethicin. The
      combined 11-residue and 20-residue trilongins generated channels that remained in
      an open state for a longer time than those formed by either one of the peptaibols
      alone. Corresponding synergy was observed in toxicokinetics. With 11-residue and
      20-residue trilongins combined 1 : 2 w/w, an effective median concentration
      (EC(50) ) of 0.6 MUg.mL(-1) was reached within 30 min, and the EC(50) shifted
      down to 0.2 MUg.mL(-1) upon extended exposure. By contrast, with 11-residue or 20
      residue trilonging separately in 30 min of exposure, the EC(50) values were 15
      and 3 MUg.mL(-1) , respectively, and shifted down to 1.5 and 0.4 MUg.mL(-1) upon
      extended exposure. This is the first report on ion-channel forming peptaibols
      with synergistic toxicity from T. longibrachiatum strains isolated from clinical
      samples.

PMID- 22994323
TI  - Randomised-controlled trials in chronic kidney disease--a call to arms!

PMID- 22994322
TI  - The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential
      of bone marrow cells.
AB  - Bone marrow (BM) has long been considered a potential stem cell source for
      cardiac repair due to its abundance and accessibility. Although previous
      investigations have generated cardiomyocytes from BM, yields have been low, and
      far less than produced from ES or induced pluripotent stem cells (iPSCs). Since
      differentiation of pluripotent cells is difficult to control, we investigated
      whether BM cardiac competency could be enhanced without making cells pluripotent.
      From screens of various molecules that have been shown to assist iPSC production
      or maintain the ES cell phenotype, we identified the G9a histone
      methyltransferase inhibitor BIX01294 as a potential reprogramming agent for
      converting BM cells to a cardiac-competent phenotype. BM cells exposed to
      BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and
      islet1, which are genes associated with embryonic cardiac progenitors. In
      contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and
      pluripotency gene expression by BM cells. Expression of cardiac-associated genes
      Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76,
      276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11
      when BM cells were pretreated with BIX01294. Immunofluorescent analysis
      demonstrated that BIX01294 exposure allowed for the subsequent display of various
      muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype
      and differentiation potential corresponded to an overall decrease in methylation
      of histone H3 at lysine9, which is the primary target of G9a histone
      methyltransferase. In summary, these data suggest that BIX01294 inhibition of
      chromatin methylation reprograms BM cells to a cardiac-competent progenitor
      phenotype.

PMID- 22994324
TI  - Evidence-based freedom: first do no harm.

PMID- 22994325
TI  - Surveys of CAM usage.

PMID- 22994326
TI  - Combination therapy an ACE inhibitor and an angiotensin receptor blocker for IgA
      nephropathy: a meta-analysis.
AB  - OBJECTIVE: The pathogenesis of IgA nephropathy (IgAN) is still unknown.
      Combination therapy with angiotensin-converting enzyme inhibitors (ACEIs) plus
      angiotensin receptor blockers (ARBs) might provide more benefits to IgAN
      patients. We conducted a systematic review to assess the efficacy of combination
      therapy for IgAN. METHODS: The MEDLINE, EMBASE, the Cochrane Library and article
      reference lists were searched for randomised clinical trials (RCTs) which
      involved combination therapy ACEI plus ARB in only one arm. A meta-analysis was
      performed on the outcomes of proteinuria and renal function in IgAN patients.
      RESULTS: Six RCTs involving 109 patients were included in the review. Combined
      treatment with ACEI plus ARB was more effective than with ACEI/ARB alone for
      reducing daily proteinuria. This did not translate into an improvement in GFR.
      Patients receiving ACEI plus ARB therapy did not have an increased risk of
      hyperkalemia. CONCLUSIONS: The current cumulative evidence suggests that
      combination therapy ACEI plus ARB may provide more benefits to IgAN patients for
      reducing daily proteinuria. Long-term effects of these agents on renal outcomes,
      and safety need to be established.

PMID- 22994327
TI  - Prevalence of complementary and alternative medicine (CAM) use by the general
      population: a systematic review and update.
AB  - OBJECTIVES: To update previous systematic reviews of 12-month prevalence of
      complementary and alternative medicine (CAM) use by general populations; to
      explore trends in CAM use by national populations; to develop and apply a brief
      tool for assessing methodological quality of published CAM-use prevalence
      surveys. DESIGN: Nine databases were searched for published studies from 1998
      onwards. Studies prior to 1998 were identified from two previous systematic
      reviews. A six-item literature-based tool was devised to assess robustness and
      interpretability of CAM-use estimates. RESULTS: Fifty-one reports from 49 surveys
      conducted in 15 countries met the inclusion criteria. We extracted 32 estimates
      of 12-month prevalence of use of any CAM (range 9.8-76%) and 33 estimates of 12
      month prevalence of visits to CAM practitioners (range 1.8-48.7%). Quality of
      methodological reporting was variable; 30/51 survey reports (59%) met four or
      more of six quality criteria. Estimates of 12-month prevalence of any CAM use
      (excluding prayer) from surveys using consistent measurement methods showed
      remarkable stability in Australia (49%, 52%, 52%; 1993, 2000, 2004) and USA (36%,
      38%; 2002, 2007). CONCLUSIONS: There was evidence of substantial CAM use in the
      15 countries surveyed. Where national trends were discernable because of
      consistent measurement, there was no evidence to suggest a change in 12-month
      prevalence of CAM use since the previous systematic reviews were published in
      2000. Periodic surveys are important to monitor population-level CAM use. Use of
      government-sponsored health surveys may enhance robustness of population-based
      prevalence estimates. Comparisons across countries could be improved by
      standardising approaches to data collection.

PMID- 22994328
TI  - Assessing the risk of stroke from neck manipulation: a systematic review.
AB  - BACKGROUND: Strokes, typically involving vertebral artery dissection, can follow
      cervical spinal manipulative therapy, and these types of stroke occur rarely.
      There is disagreement about whether a strong association between neck
      manipulation and stroke exists. An earlier systematic review found two relevant
      studies of association that used controls, which also discussed the limitations
      of the two papers. Our systematic review updates the earlier review, and aims to
      determine whether conclusive evidence of a strong association exists. METHODS:
      PRISMA guidelines for systematic reviews were followed, and the literature was
      searched using a strategy that included the terms 'neck manipulation' and
      'stroke' from the PubMed, Embase, CINAHL Plus and AMED databases. Citations were
      included if they met criteria such as being case-control studies, and dealt with
      neck manipulation and/or neck movement/positioning. Papers were scored for their
      quality, using similar criteria to the earlier review. For individual criteria,
      each study was assigned a full positive score if the criterion was satisfied
      completely. RESULTS: Four case-control studies and one case-control study, which
      included a case- crossover design, met the selection criteria, but all of them
      had at least three items in the quality assessment that failed to be completely
      positive. Two studies were assessed to be the most robustly designed, one
      indicating a strong association between stroke and various intensities of neck
      movement, including manipulation, and the other suggesting a much reduced
      relative association when using primary care practitioners' visits as controls.
      However, potential biases and confounders render the results inconclusive.
      CONCLUSION: Conclusive evidence is lacking for a strong association between neck
      manipulation and stroke, but is also absent for no association. Future studies of
      association will need to minimise potential biases and confounders, and ideally
      have sufficient numbers of cases to allow subgroup analysis for different types
      of neck manipulation and neck movement.

PMID- 22994329
TI  - Severe caloric restriction in young women during World War II and subsequent
      breast cancer risk.
AB  - AIM: The objective of the study was to examine the impact of WWII-related caloric
      restriction (CR) on subsequent breast cancer (BC) risk based on individual
      exposure experiences and whether this effect was modified by age at exposure.
      METHODOLOGY: We compared 65 breast cancer patients diagnosed between 2005-2010 to
      200 controls without breast cancer who were all members of various organizations
      for Jewish WWII survivors in Israel. All participants were Jewish women born in
      Europe prior to 1945 who lived at least 6 months under Nazi rule during WWII and
      immigrated to Israel after the war. We estimated CR using a combined index for
      hunger and used logistic regression models to estimate the association between CR
      and BC, adjusting for potential confounders. RESULTS: Women who were severely
      exposed to hunger had an increased risk of BC (OR=5.0, 95% CI= 2.3-10.8) compared
      to women who were mildly exposed. The association between CR and BC risk was
      stronger for women who were exposed at a younger age (0-7 years) compared to the
      risk of BC in women exposed at >= 14 years (OR= 2.8, 95% CI=1.3-6.3).
      CONCLUSIONS: Severe exposure to CR is associated with a higher risk for BC
      decades later, and may be generalized to other cases of severe starvation during
      childhood that may have long-term effects on cancer in adulthood.

PMID- 22994330
TI  - Glycaemic control in patients with type 2 diabetes switching from premixed
      insulin to long-acting basal insulin analogue plus oral antidiabetic drugs: an
      observational study.
AB  - AIM: To evaluate whether administration of long-acting basal insulin analogue
      plus oral antidiabetic drugs (OADs) improves glycaemic control in type 2 diabetic
      patients with glycosylated haemoglobin (HbA1c) > 7% (53 mmol/mol) under premixed
      insulin therapy. METHODS: This is a multicentre, observational, retrospective
      study performed in type 2 diabetic patients switching from premixed insulin to
      long-acting basal insulin analogue plus OADs. Data on patients' medical history
      and assessments were retrieved from patients' medical charts prior to switching
      the treatment and 6 months thereafter. RESULTS: A total of 131 evaluable patients
      were enrolled (mean age, 68.2 +/- 9.4 years; female, 65.6%; mean diabetes
      duration, 12.7 +/- 6.9 years; mean time on insulin therapy, 53.2 +/- 41.9
      months). Patients were receiving premixed insulin (once-daily, 4.7%; twice-daily,
      85.0%; thrice-daily, 10.2%), 82.4% of whom in combination with OADs (metformin,
      79.4%). After the treatment was switched, only 14.5% required intensification of
      treatment with additional preprandial insulin. HbA1c decreased -1.4% [mean +/-
      SD, 8.4 +/- 1.0% (68.7 +/- 11.4 mmol/mol) vs. 7.0 +/- 1.0% (53.6 +/- 10.9
      mmol/mol), p < 0.001] and the proportion of patients achieving HbA1c < 7% (53
      mmol/mol) increased to 52.7% (p < 0.001). The percentage of patients with
      hypoglycaemia decreased (19.2% vs. 10.8%, p < 0.05; symptomatic, 17.6% vs. 4.6%,
      p < 0.01) and body weight diminished by -1.9 kg (mean +/- SD, 78.5 +/- 14.7 kg
      vs. 76.6 +/- 13.9 kg, p < 0.05). Basal insulin plus OADs was considered more
      convenient and flexibly adapted to patients' life in 98.4% and 99.2% of patients,
      respectively. Additionally, 96.9% of patients reported being more satisfied and
      96.9% would recommend it. CONCLUSIONS: Switching the treatment from premixed
      insulin to long-acting basal insulin analogue plus OADs is a feasible and
      convenient approach to improve glycaemic control of type 2 diabetic patients
      poorly controlled with premixed insulin under routine clinical practice
      conditions.

PMID- 22994331
TI  - The psychopathological characteristics of treatment discontinuation group in 6
      month treatment with paliperidone ER.
AB  - OBJECTIVE: To examine the demographic and psychopathological characteristics of
      the treatment discontinuation group compared with patients who completed with
      paliperidone ER treatment for 6 months. METHODS: A total of 984 patients meeting
      the DSM-IV criteria for schizophrenia who switched their antipsychotics were
      recruited from 61 sites in five countries in Southeast Asia. The patients with
      early discontinuation were then compared with those who completed the 6-month
      treatment in terms of demographic and psychopathological variables at baseline
      and also at the end of the evaluation period, which included PANSS score, sleep
      quality, daytime drowsiness, PSP score, ESRS score and clinical global impression
      severity (CGI-S) score. Finally, logistic regression analysis was applied to
      determine predictive factors that were associated with discontinuation. RESULTS:
      Of 984 patients, 284 patients (28.9%) discontinued without completing the 6-month
      treatment period with paliperidone. Significant differences in patient baseline
      characteristics for the discontinuation group compared with the completion group
      were observed for gender, number of previous hospitalisations with psychosis,
      PANSS total score and all of its subscales, daytime drowsiness score, total ESRS
      score, CGI-S, PSP and Insight. Patients who completed the study period had
      significantly better scores in all psychopathology variables compared with the
      discontinuation group at the end of the evaluation period. Numbers of previous
      hospitalisations because of psychosis, being exposed with first generation
      antipsychotics, gender and PANSS total scores were found to be significant
      predictors of discontinuation. CONCLUSION: Patients who discontinued early from a
      6-month treatment period with Paliperidone have some characteristic differences
      compared with completion patients. Many factors including frequent
      hospitalisations, female gender, high PANSS score (indicating more disease
      severity) and previous exposure to first generation of antipsychotic agent might
      lead patients to discontinue from treatment.

PMID- 22994332
TI  - Factors associated with 'caregiver burden' for atrial fibrillation patients.
AB  - BACKGROUND: The burden on caregivers providing support to atrial fibrillation
      (AF) patients has not been evaluated. OBJECTIVE: To examine the interrelationship
      between unpaid caregiver, patient and thromboprophylaxis characteristics and
      caregiver burden in AF. METHODS: We conducted a cross-sectional survey study of
      AF patient-caregiver dyads recruited from cardiology clinics at an urban teaching
      hospital. Eligible patients had a diagnosis of AF, received thromboprophylaxis to
      prevent stroke, lived in the community and had an adult, unpaid, English-speaking
      caregiver. Hierarchical multivariate regression was used to evaluate the
      association between caregiver, patient and thromboprophylaxis characteristics and
      caregiver burden as measured by the 'Caregiver Reaction Assessment' (CRA).
      RESULTS: Eighty patient-caregiver dyads were surveyed. The mean +/- standard
      deviation scores for each CRA domain were 'Disrupted schedule' (2.4 +/- 1.0),
      'Financial problems' (2.1 +/- 0.8), 'Lack of family support' (1.9 +/- 0.7),
      'Health problems' (1.9 +/- 0.7) and 'Self-esteem' (0.9 +/- 0.5). Significantly
      greater caregiver burden due to 'Disrupted schedule' was seen in those spending >
      4 h/week providing care and when caring for frail, sick or disabled patients,
      with higher CHADS2 scores and requiring help with their medications. 'Financial
      problems' burden scores were significantly associated with caring for frail
      patients and those requiring more frequent office follow-up. 'Lack of family
      support' scores were inversely associated with having somebody else to help
      provide care and increased as patients CHADS2 score increased. Lower 'Health
      problem' burden scores were associated with female gender and higher scores with
      the need to spend > 4 h/week providing care. CONCLUSION: The greatest burden to
      caregivers of AF patients occurs due to schedule disruption.

PMID- 22994333
TI  - Validation and psychometric properties of Chinese version of SF-36 in patients
      with hypertension, coronary heart diseases, chronic gastritis and peptic ulcer.
AB  - BACKGROUND: The SF-36 is widely used as a significant health outcome or quality
      of life indicator and validated in many languages versions including Chinese. But
      the Chinese version of the SF-36 (CSF-36) is rarely used for those patients with
      hypertension, coronary heart diseases, chronic gastritis and peptic ulcer in
      China. Therefore, the CSF-36 needs to be validated in patients with chronic
      diseases. OBJECTIVES: This paper is aimed to validate the CSF-36 using an in
      patient sample of four chronic diseases from mainland China, with focusing on
      psychometric properties. METHODS: The CSF-36 was used in a longitudinal study
      consisting of 534 patients in these four chronic disease groups. The psychometric
      properties of the scale were evaluated by indicators such as validity and
      reliability coefficients Cronbach alpha, Pearson r, standardized response mean
      employing correlational analyses, multi-trait scaling analysis, t-tests, factor
      analyses and structural equation models. RESULTS: Test-retest reliability
      coefficients for all domains were higher than 0.80 with a range of 0.83 to 0.96;
      the internal consistency (alpha) for most domains was higher than 0.70. Five of
      the eight domains as well as the Physical and Mental Health subscale summaries
      all had statistically significant changes after treatment with the SRM ranging
      from 0.18 to 0.28. CONCLUSION: The CSF-36 showed good validity and reliability
      but small responsiveness when used in patients. It is a good and useful
      instrument for patients with chronic disease at some situations.

PMID- 22994334
TI  - Knowledge, attitudes and barriers regarding vaccination against hepatitis A and B
      in patients with chronic hepatitis C virus infection: a survey of family medicine
      and internal medicine physicians in the United States.
AB  - BACKGROUND: Although vaccination against hepatitis A virus (HAV) and hepatitis B
      virus (HBV) is recommended for all patients with chronic hepatitis C virus (HCV)
      infection, physician vaccination practices are suboptimal. Since training for
      family medicine (FM) and internal medicine (IM) physicians differ, we
      hypothesised that there are differences in knowledge, attitudes and barriers
      regarding vaccination against HAV and HBV in patients with chronic HCV between
      these two groups. METHODS: A two-page questionnaire was mailed to 3000 primary
      care (FM and IM) physicians randomly selected from the AMA Physician Masterfile
      in 2005. The survey included questions about physician demographics, knowledge
      and attitudes regarding vaccination. RESULTS: Among the 3000 physicians surveyed,
      1209 (42.2%) returned completed surveys. There were no differences between
      respondents and non-respondents with regard to age, gender, geographic location
      or specialty. More FM than IM physicians stated that HCV+ patients should not be
      vaccinated against HAV (23.7% vs. 11.8%, p < 0.001) or HBV (21.9% vs. 10.6%, p <
      0.001). FM physicians were also less likely than IM physicians to usually/always
      test HCV+ patients for immunity against HAV (33.9% vs. 48.6%, p < 0.001) or
      against HBV (50.8% vs. 68.0%, p < 0.001). There were numerous barriers to HAV and
      HBV vaccination identified. The median number of barriers was 3 for FM physicians
      and 2 for IM physicians (p < 0.001). CONCLUSIONS: Despite recommendations to
      vaccinate against HAV and HBV in patients with chronic HCV infection, physicians
      often do not test or vaccinate susceptible individuals. Interventions are needed
      to overcome the barriers identified and improve vaccination rates.

PMID- 22994335
TI  - Retention rate of selegiline in early Parkinson's disease: a retrospective
      survey.

PMID- 22994336
TI  - High rates of dyslipidaemia among indigenous argentinean children living at high
      altitudes.

PMID- 22994337
TI  - Asymmetric addition of alkoxy ethynyl anion to chiral N-sulfinyl imines.
AB  - The addition of lithiated ynol ethers to chiral N-sulfinyl imines proceeds in
      high yield and diastereoselectivity. The selectivity is completely reversed by
      the addition of boron trifluoride. These alkoxypropargyl sulfinamides can be
      reduced to afford enol ethers, selectively oxidized to busyl derivatives, or the
      ynol ether can be hydrolyzed to afford beta-amino esters.

PMID- 22994339
TI  - Antioxidant intake and allergic disease.

PMID- 22994340
TI  - H(1)-antihistamines and urticaria: how can we predict the best drug for our
      patient?
AB  - Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult
      condition to treat. Consequently, clinicians need to use the best H(1)
      antihistamines currently available and the pharmaceutical industries need to keep
      developing H(1)-antihistamines that are more effective than the ones we have
      today. To do this we need to be able to compare the clinical efficacy of both
      established and new drugs. Obviously, the ideal way to do this is to use head-to
      head studies in CSU. However, such studies are extremely expensive and, in the
      case of novel molecules, have ethical and logistical problems. Consequently, we
      need to have predictive models. Although determination of Ki, an indicator of the
      in vitro potency of an H(1)-antihistamine, may help in the initial selection of
      candidate molecules, the large differences in volume of distribution and tissue
      accumulation in humans, precludes this from being a good predictor of clinical
      efficacy in CSU. From the data reviewed in this article, especially the direct
      comparative data of desloratadine and levocetirizine in weal and flare studies
      and CSU, weal and flare response would appear to be the best indicator we have of
      effectiveness of H(1)-antihistamines in clinical practice. However, it must be
      pointed out that the conclusion is, essentially, based on detailed comparisons of
      two drugs in studies sponsored by pharmaceutical companies. Consequently, to
      confirm the conclusions of this review, a multicentre study independent from the
      influence of pharmaceutical companies should be commissioned to compare the speed
      of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in
      chronic spontaneous urticaria and against histamine-induced weal and flare
      responses in the same patients so that we have a clear understanding of the
      predictive value of our models.

PMID- 22994342
TI  - Identity of the fungal species present in the homes of asthmatic children.
AB  - BACKGROUND: Fungal exposures are believed to play an important role in the
      development of asthma and atopy, accounting for increased asthmatic symptoms and
      severe asthma exacerbation. Indoor fungal species vary both in taxa and
      concentration in different residences and in different regions. OBJECTIVES: We
      explored the fungal species spectrum in 88 homes with at least one asthmatic
      child in the Middle West region of the United States mostly during late spring
      and fall season in comparison with 85 homes that did not contain an asthmatic
      child during flu season. METHODS: The average fungal spore counts per cubic metre
      of air in the bedroom of the enrolled child, the main living spaces and outdoor
      environments, and the culturable fungal colony-forming units per cubic metre of
      air samples in the main living space from each home were measured. RESULTS: The
      results indicated that Cladosporium, Penicillium, Aspergillus, Basidiospores,
      Epicoccum and Pithomyces were found in more asthmatic homes than in homes without
      an asthmatic child or existed in higher concentration in asthmatic homes than in
      homes without an asthmatic child even after adjusting outdoor spore
      concentration. The results for culturable fungal species confirmed most of these
      findings even after adjusting for seasonal factors. Although Alternaria was
      commonly found in both kinds of homes, there was no significant difference in
      detection rate or concentration of Alternaria between asthmatic homes and homes
      without an asthmatic child by either spore counting or culturable airborne
      detection. CONCLUSION AND CLINICAL RELEVANCE: Since many allergens have been
      identified in these fungal species, identifying and controlling these fungal
      species in asthmatic homes might be expected to improve asthma care and benefit
      asthmatic children.

PMID- 22994341
TI  - Fetal growth and risk of childhood asthma and allergic disease.
AB  - INTRODUCTION: Early genetic and environmental factors have been discussed as
      potential causes for the high prevalence of asthma and allergic disease in the
      western world, and knowledge on fetal growth and its consequence on future health
      and disease development is emerging. OBJECTIVE: This review article is an attempt
      to summarize research on fetal growth and risk of asthma and allergic disease.
      Current knowledge and novel findings will be reviewed and open research questions
      identified, to give basic scientists, immunologists and clinicians an overview of
      an emerging research field. METHODS: PubMed-search on pre-defined terms and cross
      references. RESULTS: Several studies have shown a correlation between low birth
      weight and/or gestational age and asthma and high birth weight and/or gestational
      age and atopy. The exact mechanism is not yet clear but both environmental and
      genetic factors seem to contribute to fetal growth. Some of these factors are
      confounders that can be adjusted for, and twin studies have been very helpful in
      this context. Suggested mechanisms behind fetal growth are often linked to the
      feto-maternal circulation, including the development of placenta and umbilical
      cord. However, the causal link between fetal growth restriction and subsequent
      asthma and allergic disease remains unexplained. New research regarding the catch
      up growth following growth restriction has posited an alternative theory that
      diseases later on in life result from rapid catch-up growth rather than
      intrauterine growth restriction per se. Several studies have found a correlation
      between a rapid weight gain after birth and development of asthma or wheezing in
      childhood. CONCLUSION AND CLINICAL RELEVANCE: Asthma and allergic disease are
      multifactorial. Several mechanisms seem to influence their development.
      Additional studies are needed before we fully understand the causal links between
      fetal growth and development of asthma and allergic diseases.

PMID- 22994344
TI  - Pro-inflammatory and Th2-type cytokine responses in PBMC in infants are
      associated with parental smoking.
AB  - BACKGROUND: During infancy, a disturbed cytokine balance leads to an atopic
      immune response. Many risk factors have been associated with the development of
      atopy. These include parental smoking, elevated cord blood IgE, early exposure to
      pets and family history of atopy, but the knowledge of their impact on cytokine
      balance is limited. OBJECTIVE: To assess the cytokines induced by mitogen in
      peripheral blood mononuclear cells (PBMC) of infants at 3 months and 12 months of
      age and their potential association with fatty acid (FA) intervention, parental
      atopy, atopic dermatitis and parental smoking. METHODS: Infants from an
      intervention study using black currant seed oil (BCSO, n = 34) or placebo (n =
      34) were included. PBMC samples were taken at the age of 3 and 12 months. Signs
      of atopic dermatitis and parental smoking were registered. PBMC were isolated
      from heparinized blood samples, stimulated with ConcanavalinA mitogen and the
      cytokine responses were detected at 72 h of stimulation by Luminex technology.
      RESULTS: Children of smoking parents had elevated levels of IL-4 (P = 0.0004), IL
      5 (P = 0.0002), IFN-gamma (P = 0.039) and TNF (P = 0.0003) at 12 months of age.
      Children who had atopic dermatitis by the age of 3 months showed elevated levels
      of IL-5 at 3 months (P = 0.0027) and 12 months of age (P = 0.022). The production
      of TNF at the age of 3 months was higher (P = 0.010) and the production of IL-12
      at the age of 12 months was lower (P = 0.025) in infants whose parents were
      atopic. BCSO intervention did not have any effect on any cytokine production or
      mRNA expression. CONCLUSION: Children of smoking parents had highly significantly
      elevated levels of Th2-type cytokines IL-4, IL-5 and pro-inflammatory cytokine
      TNF. The detrimental effects of parental smoking on the child's immune function
      should lead us to pay more attention to supporting parents to stop smoking.

PMID- 22994343
TI  - Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in
      fatal asthma.
AB  - BACKGROUND: Airway inflammation in asthma involves innate immune responses. Toll
      like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be
      involved in airway inflammation, but their expression in asthmatics' both large
      and small airways has not been investigated. OBJECTIVE: To analyse the expression
      of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare
      their expression in smoking and non-smoking asthmatics; to investigate whether
      TLR expression is associated with eosinophilic or neutrophilic airway
      inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae
      infection. METHODS: Using immunohistochemistry and image analysis, we
      investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of
      24 victims of fatal asthma, FA, (13 non-smokers, 11 smokers) and nine deceased
      control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and
      12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung
      tissue were analysed using real-time polymerase chain reaction. Airway
      eosinophils and neutrophils were measured in all subjects. RESULTS: Fatal asthma
      patients had higher TLR2 in the epithelial and outer layers of large and small
      airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the
      inner and outer layers of the small airways than non-smoking asthmatics. TSLP was
      increased in the epithelial and outer layers of the large airways of FA. FA
      patients had greater TLR3 expression in the outer layer of large airways and
      greater TLR4 expression in the outer layer of small airways. Eosinophilic airway
      inflammation was associated with TLR expression in the epithelium of FA. No
      bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small
      difference in TLR3 expression. CONCLUSIONS AND CLINICAL RELEVANCE: Increased
      expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute
      inflammation surrounding asthma deaths.

PMID- 22994345
TI  - Comparison of Timothy grass pollen extract- and single major allergen-induced
      gene expression and mediator release in airway epithelial cells: a meta-analysis.
AB  - BACKGROUND: Seasonal allergic rhinitis (AR) is a global health problem and its
      prevalence has increased considerably in the last decades. As the allergic
      response with its clinical manifestations is triggered by only a few proteins
      within natural extracts, there is an increasing tendency for single-component
      resolved diagnosis and immunotherapy. OBJECTIVE: As natural exposure is not to
      single proteins, but to complex mixtures of molecules, we were interested in
      comparing the activation of respiratory epithelial cells induced by the purified
      major allergen Phl p 1 with the induction caused by a complete extract of Timothy
      grass pollen (GPE). METHODS: NCI-H292 cells were exposed to GPE or Ph1 p 1 for 24
      h, isolated RNA and cell culture supernatants were used for microarray analysis,
      multiplex enzyme-linked immunosorbant assay (ELISA) and subsequent analysis.
      RESULTS: We found 262 genes that showed a GPE-induced change of at least 3-fold,
      whereas Ph1 p 1-stimulation resulted in 71 genes with a fold induction of more
      than 3-fold. Besides genes that were regulated by both stimuli, we also detected
      genes displaying an opposite response after stimulation, suggesting that GPE
      might be more than purified major allergens with regard to induced immune
      responses. CONCLUSIONS AND CLINICAL RELEVANCE: Additional components within GPE
      and the resulting modulation of general processes affecting gene transcription
      and signalling pathways might be crucial to maintain/overcome the diseased
      phenotype and to induce the influx of cells contributing to late-phase allergic
      responses. When the initial process of sensitization is the matter of interest or
      late-phase allergic responses, one might miss important immune modulatory
      molecules and their interaction with allergens by applying single components
      only.

PMID- 22994347
TI  - Trends in cutaneous sensitization in the first 18 years of life: results from the
      1989 Isle of Wight birth cohort study.
AB  - BACKGROUND: Skin prick testing (SPT) is fundamental to the practice of clinical
      allergy identifying relevant allergens and predicting the clinical expression of
      disease. There are only limited data on the natural history of SPT results over
      childhood and adolescence. OBJECTIVE: We aimed to describe the natural history of
      SPT and patterns of sensitization over childhood and adolescence. METHODS: The
      1989 Isle of Wight birth cohort (1456 participants) was followed up at 1, 2, 4,
      10 and 18 years. SPT was undertaken from 4 years. RESULTS: SPT was performed on
      980 (80%), 1036 (75%) and 853 (65%) of participants at 4, 10 and 18 years. The
      prevalence of sensitization to any allergen at these time-points was 19.7%, 26.9%
      and 41.3% respectively. At each time-point, boys were significantly more likely
      to be sensitized (P < 0.016) and sensitization significantly increased over
      childhood and adolescence (average annual increase of 7%). Some children outgrew
      their sensitization. The rate of sensitization to most individual allergens
      increased over childhood and adolescence. A configural frequency analysis showed
      that whether an individual was sensitizated was relatively fixed over childhood
      and adolescence. Cluster analysis at 4 years demonstrated four major groups of
      individuals with similar co-sensitization to specific allergens. Children who
      were sensitized at age 4 years generally went onto become sensitized to
      additional allergens at 10 and 18 years. CONCLUSIONS AND CLINICAL RELEVANCE:
      Allergic sensitization continues to increase over childhood into adolescence
      although the majority of children who were not sensitized at 4 years remain non
      sensitized throughout childhood and adolescence. The presence of sensitization at
      4 years predicted later sensitization to additional allergens.

PMID- 22994346
TI  - Antioxidant intake and allergic disease in children.
AB  - BACKGROUND: Antioxidant intake may reduce the risk of allergic disease by
      protecting against oxidative tissue damage. Major sources of antioxidants in the
      Western world are fruits, vegetables (vitamin C, beta-carotene, alpha
      tocopherol), meat and milk (selenium, magnesium, zinc). Children may exclude or
      eat less of some fruits and vegetables due to cross-reactivity between pollen and
      these foods, complicating assessment of causal relationships. OBJECTIVE: To
      investigate the association between dietary antioxidant intake and allergic
      disease, taking potential reverse causation into account. METHODS: Data on 2442 8
      year-old children from the Swedish birth cohort study BAMSE were analysed.
      Children with completed parental questionnaires on exposures and health,
      including a food-frequency questionnaire and who provided a blood sample were
      included. Associations between antioxidant intake during the past year and
      current allergic disease were analysed using logistic regression. RESULTS: An
      inverse association was observed between intake of beta-carotene and rhinitis
      (OR(adj), highest vs. lowest quartile, 0.67, 95% CI 0.49-0.93). Magnesium intake
      was inversely related to asthma (OR(adj), 0.65, 95% CI 0.42-1.00) and atopic
      sensitisation (OR(adj), 0.78, 95% CI 0.61-1.00). Following exclusion of children
      who avoided certain fruits, vegetables or milk due to allergic symptoms (n =
      285), the inverse association remained between magnesium intake and asthma
      (OR(adj), 0.58, 95% CI 0.35-0.98), whereas all other associations became non
      significant. CONCLUSION AND CLINICAL RELEVANCE: Diet modifications due to allergy
      may affect the antioxidant intake and needs to be considered when investigating
      the relationship between diet and allergic disease. Magnesium intake seems to
      have a protective effect on childhood asthma.

PMID- 22994348
TI  - Absence of IgE neosensitization in house dust mite allergic patients following
      sublingual immunotherapy.
AB  - BACKGROUND: The impact of sublingual immunotherapy (SLIT) on IgE neosensitization
      remains to be evaluated in large cohorts of patients. OBJECTIVES: The aim of this
      study was to assess the dynamics of antibody responses induced in patients with
      allergic rhinitis during a 12-month treatment with sublingual tablets of house
      dust mites (HDM) allergen extracts. METHODS: Antibody responses were assessed in
      relationship with neosensitization and clinical benefit in sera from 509 European
      house dust mite-allergic patients before and after 1 year of daily sublingual
      immunotherapy, using tablets containing Dermatophagoides pteronyssinus plus D
      farinae extracts or placebo (ClinicalTrials.gov NCT00674700). Patients were
      followed for one additional year after treatment cessation. IgE and IgG4
      antibodies specific for mite extracts or purified group 1, 2 and 10 allergens
      were assessed using Immulite, Immunocap and ISAC assays. RESULTS: After 1 year of
      SLIT, mite-specific IgE and IgG4 titres increased by 1.5-fold and fourfold,
      respectively, in the active, but not in the placebo group. A strong IgG4
      induction occurred in a subgroup (i.e. 10-15%) of "immunoreactive" patients,
      without any correlation with improvement in the average adjusted symptom score.
      Pre-existing IgE levels to purified mite allergens were not impacted during
      immunotherapy, and no de novo IgE responses to group 1, 2, 10 allergens were
      induced in patients who were unsensitized prior to immunotherapy. Similarly, no
      IgE neosensitization to wheat germ or yeast components used in the mite culture
      medium was observed. CONCLUSIONS AND CLINICAL RELEVANCE: We document in a cohort
      of 509 patients followed over a 2-year period that SLIT does not induce any IgE
      neosensitization to allergens contained in the vaccine, such as groups 1, 2 as
      well as the food-related group 10 allergen. This observation further corroborates
      the safer safety profile of SLIT over SCIT.

PMID- 22994349
TI  - Contribution of regulatory T cells to alleviation of experimental allergic asthma
      after specific immunotherapy.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) has been used since 1911, yet
      its mechanism of action remains to be elucidated. There is evidence indicating
      that CD4(+)FOXP3(+) regulatory T cells (Treg cells) are induced during SIT in
      allergic patients. However, the contribution of these cells to SIT has not been
      evaluated in vivo. OBJECTIVE: To evaluate the in vivo contribution of (i) CD4(+)
      CD25(+) T cells during SIT and of (ii) SIT-generated inducible FOXP3(+) Treg
      cells during allergen exposure to SIT-mediated suppression of asthmatic
      manifestations. METHODS: We used a mouse model of SIT based on the classical OVA
      driven experimental asthma. Treg cells were quantified by flow cytometry 24 and
      96 h post SIT treatment. We depleted CD4(+) CD25(+) T cells prior to SIT, and
      CD4(+)FOXP3(+) T cells prior to allergen challenges to study their contribution
      to the suppression of allergic manifestations by SIT treatment. RESULTS: Our data
      show that depletion of CD4(+)CD25(+) T cells at the time of SIT treatment
      reverses the suppression of airway hyperresponsiveness (AHR), but not of airway
      eosinophilia and specific IgE levels in serum. Interestingly, the number of
      CD4(+)CD25(+)FOXP3(+) T cells is transiently increased after SIT in the spleen
      and blood, suggesting the generation of inducible and presumably allergen
      specific Treg cells during treatment. Depletion of CD4(+)FOXP3(+) Treg cells
      after SIT treatment partially reverses the SIT-induced suppression of airway
      eosinophilia, but not of AHR and serum levels of specific IgE. CONCLUSION AND
      CLINICAL RELEVANCE: We conclude that SIT-mediated tolerance induction towards AHR
      requires CD4(+)CD25(+) T cells at the time of allergen injections. In addition,
      SIT generates CD4(+)CD25(+)FOXP3(+) T cells that contribute to the suppression of
      airway eosinophilia upon allergen challenges. Therefore, enhancing Treg cell
      number or their activity during and after SIT could be of clinical relevance to
      improve the therapeutic effects of SIT.

PMID- 22994350
TI  - Lipid transfer protein syndrome: clinical pattern, cofactor effect and profile of
      molecular sensitization to plant-foods and pollens.
AB  - BACKGROUND: Multiple plant-food sensitizations with a complex pattern of clinical
      manifestations are a common feature of lipid transfer protein (LTP)-allergic
      patients. Component-resolved diagnosis permits the diagnosis of the allergen
      sensitization profile. OBJECTIVE: We sought to clinically characterize and
      describe the plant-food and pollen molecular sensitization profile in patients
      with LTP syndrome. METHODS: Forty-five subjects were recruited, after being
      diagnosed with multiple plant-food allergies sensitized to LTP, but not to any
      other plant-food allergen, according to the molecular allergen panel tested (Pru
      p 3 (LTP), Pru p 1 (Bet v 1-like), Pru p 4 (profilin) and those included in a
      commercial microarray of 103 allergenic components). IgE-mediated food-allergy
      symptoms and pollinosis were collected. Patients were skin prick tested with a
      plant-food and pollens panel, and specific IgE to Tri a 14 was evaluated.
      RESULTS: A heterogeneous group of plant-foods was involved in local and systemic
      symptoms: oral allergy syndrome (75.6%), urticaria (66.7%), gastrointestinal
      disorders (55.6%) and anaphylaxis (75.6%), 32.4% of which were cofactor dependent
      (Non-Steroidal Anti-inflammatory Drugs, exercise). All tested subjects were
      positive to peach and Pru p 3, Tri a 14 and to some of the LTPs included in the
      microarray. Pollinosis was diagnosed in 75.6% of subjects, with a broad spectrum
      of pollen and pollen-allergen sensitization. Plane tree and mugwort were the
      statistically significant pollens associated with Pru p 3. CONCLUSIONS AND
      CLINICAL RELEVANCE: Several plant-foods, taxonomically unrelated, independent of
      peach involvement, are implicated in LTP syndrome. Local symptoms should be
      evaluated as a risk marker for anaphylaxis because they are frequently associated
      with cofactor-dependent anaphylaxis. The association of these symptoms with
      pollinosis, especially plane tree pollinosis, could be part of this syndrome in
      our area.

PMID- 22994351
TI  - Role of fungal colonization for sensitization in asthma.

PMID- 22994354
TI  - Understanding the relationship between brain gene expression and social behavior:
      lessons from the honey bee.
AB  - Behavior is a complex phenotype that is plastic and evolutionarily labile. The
      advent of genomics has revolutionized the field of behavioral genetics by
      providing tools to quantify the dynamic nature of brain gene expression in
      relation to behavioral output. The honey bee Apis mellifera provides an excellent
      platform for investigating the relationship between brain gene expression and
      behavior given both the remarkable behavioral repertoire expressed by members of
      its intricate society and the degree to which behavior is influenced by heredity
      and the social environment. Here, we review a linked series of studies that
      assayed changes in honey bee brain transcriptomes associated with natural and
      experimentally induced changes in behavioral state. These experiments demonstrate
      that brain gene expression is closely linked with behavior, that changes in brain
      gene expression mediate changes in behavior, and that the association between
      specific genes and behavior exists over multiple timescales, from physiological
      to evolutionary.

PMID- 22994355
TI  - Identity by descent between distant relatives: detection and applications.
AB  - Short segments of identity by descent (IBD) between individuals with no known
      relationship can be detected using genome-wide single nucleotide polymorphism
      data and recently developed statistical methodology. Emerging applications for
      the detected IBD segments include IBD mapping, haplotype phase inference,
      genotype imputation, and inference of population structure. In this review, we
      explain the principles behind methods for IBD segment detection, describe
      recently developed methods, discuss approaches to comparing methods, and give an
      overview of applications.

PMID- 22994356
TI  - Memories from the polycomb group proteins.
AB  - The first genes composing the Polycomb group (PcG) were identified 50 years ago
      in Drosophila melanogaster as essential developmental functions that regulate the
      correct segmental expression of homeotic selector genes. In the past two decades,
      what was initially described as a large family of chromatin-associated proteins
      involved in the maintenance of transcriptional repression to maintain cellular
      memory of homeotic genes turned out to be a highly conserved and sophisticated
      network of epigenetic regulators that play key roles in multiple aspects of cell
      physiology and identity, including regulation of all developmental genes, cell
      differentiation, stem and somatic cell reprogramming and response to
      environmental stimuli. These myriad phenotypes further spread interest for the
      contribution that PcG proteins revealed in the pathogenesis and progression of
      cancer and other complex diseases. Recent novel insights have increasingly
      clarified the molecular regulatory mechanisms at the basis of PcG-mediated
      epigenetic silencing and opened new visions about PcG functions in cells. In this
      review, we focus on the multiple modes of action of the PcG complexes and
      describe their biological roles.

PMID- 22994357
TI  - Paleopopulation genetics.
AB  - Paleopopulation genetics is a new field that focuses on the population genetics
      of extinct groups and ancestral populations (i.e., populations ancestral to
      extant groups). With recent advances in DNA sequencing technologies, we now have
      unprecedented ability to directly assay genetic variation from fossils. This
      allows us to address issues, such as past population structure, changes in
      population size, and evolutionary relationships between taxa, at a much greater
      resolution than can traditional population genetics studies. In this review, we
      discuss recent developments in this emerging field as well as prospects for the
      future.

PMID- 22994358
TI  - Clinical outcomes of multidisciplinary pain rehabilitation among african american
      compared with caucasian patients with chronic pain.
AB  - OBJECTIVES: The primary aim of this study was to determine if the immediate
      outcomes of multidisciplinary pain rehabilitation were different for African
      Americans compared with Caucasians. DESIGN: A retrospective repeated measures
      design was used, and all analyses were adjusted for marital and employment
      status, years of education, and pain duration. SETTING: Multidisciplinary pain
      rehabilitation center. SUBJECTS: Each African American (N = 40) consecutively
      admitted to a multidisciplinary pain rehabilitation program was matched with
      three Caucasians (N = 120) on age, sex, and treatment dates. INTERVENTION: A 3
      week outpatient multidisciplinary pain rehabilitation program. OUTCOME MEASURES:
      The Multidimensional Pain Inventory, Short Form-36 Health Status Questionnaire,
      Center for Epidemiologic Studies-Depression scale, and Pain Catastrophizing Scale
      were administered at admission and dismissal. RESULTS:  At baseline, African
      Americans had greater pain severity (P < 0.001) and poorer physical function
      compared with Caucasians (P < 0.001). At program completion, African Americans
      had greater pain severity (P < 0.001) and poorer measures of life interference (P
      = 0.004), perceived control (P = 0.013), affective distress (P < 0.001), role
      physical (P = 0.001) and role emotional function (P = 0.001), physical (P <
      0.001) and social function (P = 0.002), general health (P = 0.005), depression (P
      < 0.001), and pain catastrophizing (P < 0.001). A repeated measures analysis
      demonstrated a time by race interaction effect for pain interference (P = 0.038),
      affective distress (P = 0.019), role physical function (P = 0.007), social
      function (P = 0.029), and depression (P = 0.004), indicating African Americans
      experienced less improvement compared with Caucasians. CONCLUSIONS: The results
      of this study highlight an under-recognized health disparity which provides the
      basis for developing targeted interventions aimed at improving the clinical
      outcomes of African Americans with chronic pain.

PMID- 22994359
TI  - Attenuation of early liver fibrosis by pharmacological inhibition of smoothened
      receptor signaling.
AB  - Hedgehog (Hh) signaling is involved in the pathogenesis of liver fibrosis. It has
      been previously shown that Hh-inhibitor cyclopamine (CYA) can reduce liver
      fibrosis in rats. However, CYA is not stable in vivo, which limits its clinical
      application. This study compares the antifibrotic potential of two known Hh
      antagonists, vismodegib (GDC-0449, abbreviated to GDC) and CYA. GDC is a
      synthetic molecule presently in clinical cancer trials and has been reported to
      be safe and efficacious. These drugs attenuated early liver fibrosis in common
      bile duct ligated rats, improved liver function, and prevented hepatic stellate
      cell (HSC) activation, thereby suppressing epithelial to mesenchymal transition
      (EMT). While both CYA and GDC increased the number of proliferating cell nuclear
      antigen positive liver cells in vivo, only CYA increased Caspase-3 expression in
      HSCs in rat livers, suggesting that while GDC and CYA effectively attenuate early
      liver fibrosis, their hepatoprotective effects may be mediated through different
      modes of action. Thus, GDC has the potential to serve as a new therapeutic agent
      for treating early liver fibrosis.

PMID- 22994360
TI  - Concentration measurement of length-fractionated colloidal single-wall carbon
      nanotubes.
AB  - The determination of the carbon concentration of single-wall carbon nanotubes
      (SWCNTs) in a given dispersion is a basic requirement for many studies. The
      commonly used optical absorption-based concentration measurement is complicated
      by the spectral change due to variations in nanotube chirality and length. In
      particular, the origin of the observed length-dependent spectral change and its
      effect on concentration determination has been the subject of considerable
      debate. Here, we use length-fractionated DNA-wrapped SWCNTs to establish the
      relationship between SWCNT carbon concentration and optical absorption spectra by
      directly quantifying the amount of wrapping DNA and, independently, the
      DNA/carbon nanotube mass ratio. We find that SWCNT carbon concentrations derived
      from either the E(11) peak or spectral baseline deviate significantly from the
      SWCNT carbon concentrations derived from the DNA measurement method. Instead,
      SWCNT carbon concentrations derived from the spectral integration of the E(11)
      optical transition region match most closely with the DNA-derived SWCNT carbon
      concentrations. We also observe that shorter SWCNT fractions contain more curved
      carbon nanotubes, and propose that these defective nanotubes are largely
      responsible for the observed spectral variation with nanotube length.

PMID- 22994361
TI  - Cerebral astroblastoma in an adult: an immunohistochemical, ultrastructural and
      genetic study.
AB  - Astroblastoma is a rare glial tumor of unknown origin, usually affecting the
      cerebral hemispheres of children and young adults. Here we report an unusual
      cerebral tumor in a 60-year-old woman. On MRI, the tumor appeared as a well
      circumscribed lesion in the left frontal lobe. Histopathologically, it was
      composed of rounded eosinophilic cells, and was divisible into two areas. One
      area was characterized by a collection of GFAP-positive cells around sclerotic
      blood vessels (astroblastic pseudorosettes and perivascular hyalinization), and
      had a Ki-67 labeling index of 2.8%. However, the other area was highly cellular,
      showing many GFAP-negative cells often with a rhabdoid appearance, mitoses and a
      Ki-67 index of 15.7%. Thus, a final diagnosis of malignant astroblastoma was
      made. In both areas of the tumor, nearly all the cells were positive for
      epithelial membrane antigen, and many were positive for oligodendrocyte
      transcription factor 2 (Olig2). Focal expression of cytokeratin was also evident.
      With regard to genetic markers, the tumor cells were positive for INI1 and
      negative for mutant IDH1. The p53 labeling index was <1%. Ultrastructurally, the
      presence of intra- and intercellular lumina with microvilli was a feature. DNA
      examination of IDH1/2 and TP53 showed no mutations. In conclusion, although
      ependymal features were evident ultrastructurally in the present tumor, the
      immunohistochemical expression pattern of Olig2 was that of diffuse astrocytoma.
      On the other hand, the absence of mutations in both IDH1/2 and TP53 suggested
      that the present tumor was not a purely astrocytic neoplasm. Further studies,
      including molecular and genetic analyses, will provide insight into the
      histogenesis of astroblastoma.

PMID- 22994364
TI  - Discussion of "letter to the editor: standardized use of the terms sedentary and
      sedentary behaviours" - sitting and reclining are different states.

PMID- 22994363
TI  - A developmental look at the attentional system in the at risk and first episode
      of psychosis: age related changes in attention along the psychosis spectrum.
AB  - INTRODUCTION: Neurodevelopmental processes of adolescence, when superimposed on a
      vulnerable brain, may produce additive effects reflecting the subthreshold
      psychotic symptoms, cognitive, and functional deterioration that are the hallmark
      of the early stages of schizophrenia. METHODS: As part of a longitudinal study,
      we investigated Continuous Performance Task, Identical Pairs Version (CPT-IP)
      performance in a sample of 301 participants (at risk for psychosis: 109; first
      episode-FE: 90; and controls: 102). Performance across groups was compared using
      d' of fast and slow, spatial and verbal conditions over two time points. Age
      effects were investigated using a regression model. RESULTS: Across all four CPT
      IP conditions FE patients performed significantly worse than controls while AR
      individuals significantly differed from healthy subjects in the verbal condition.
      Age-related performance associations across groups significantly differed in the
      slow verbal condition because the FE sample did not show a significant
      association with increasing age like the AR and NC samples. CPT performance was
      stable over time. CONCLUSIONS: Sustained attention in the putative prodrome of
      psychosis is not only impaired but associated with age. Research focusing on
      cognitive and neurobiological age-related changes can help to address fundamental
      questions about the nature of the disorder, including whether the underlying
      pathophysiology of early psychosis is static or deteriorating.

PMID- 22994362
TI  - Propranolol use in PHACE syndrome with cervical and intracranial arterial
      anomalies: collective experience in 32 infants.
AB  - The objective of this retrospective study of patients evaluated between July 2008
      and October 2011 in seven pediatric dermatology centers was to combine collective
      clinical experience using oral propranolol therapy in 32 infants with PHACE
      syndrome (Posterior fossa [brain malformations present at birth], Hemangioma
      [usually covering a large area of the skin of the head or neck >5 cm]; Arterial
      lesions [abnormalities of the blood vessels in the neck or head]; Cardiac
      abnormalities or aortic coarctation [abnormalities of the heart or blood vessels
      that are attached to the heart]; Eye abnormalities) with cervical or intracranial
      arterial anomalies. Patients were given an average daily dose of oral propranolol
      of 1.8 mg/kg divided two or three times per day for an average duration of 12.3
      months. The main outcome measure was adverse neurologic events. Seven (22%)
      patients were categorized as being at higher risk for stroke, defined on magnetic
      resonance imaging as severe, long-segment narrowing or nonvisualization of major
      cerebral or cervical vessels without anatomic evidence of collateral circulation,
      often in the presence of concomitant cardiovascular comorbidities. Only one
      patient developed a change in neurologic status during propranolol treatment:
      mild right hemiparesis that remained static and improved while propranolol was
      continued. An additional three patients had worsening hemangioma ulceration or
      tissue necrosis during therapy. This is the largest report thus far of patients
      with PHACE syndrome treated with propranolol. Although no catastrophic neurologic
      events occurred, serious complications, particularly severe ulcerations, were
      seen in a minority of patients, and given the sample size, we cannot exclude the
      possibility that propranolol could augment the risk of stroke in this population.
      We propose radiologic criteria that may prove useful in defining PHACE patients
      as being at high or standard risk for stroke. We continue to advise caution in
      using systemic beta-blockers, particularly for children with vascular anomalies
      at higher risk for stroke. Use of the lowest possible dosage, slow dosage
      titration, three times per day dosing to minimize abrupt changes in blood
      pressure, and close follow-up, including neurologic consultation as needed, are
      recommended.

PMID- 22994366
TI  - Tromso eye study: prevalence and risk factors of diabetic retinopathy.
AB  - PURPOSE: To determine the prevalence of visual impairment, retinopathy and
      macular oedema, and assess risk factors for retinopathy in persons with diabetes.
      METHODS: The present study included 514 participants with diabetes aged 46-87
      years from the Tromso Eye Study, a sub-study of the population-based Tromso Study
      in Norway. Visual acuity was measured using an auto-refractor. Retinal images
      from both eyes were graded for retinopathy and macular oedema. We collected data
      on risk factor exposure from self-report questionnaires, clinical examinations,
      laboratory measurements and case note reviews. Regression models assessed the
      cross-sectional relationship between potential risk factors and diabetic
      retinopathy. RESULTS: The prevalence of visual impairment (corrected Snellen
      visual acuity <20/60 in the better-seeing eye) was 1.6%. The prevalence of
      diabetic retinopathy was 26.8% and macular oedema 3.9%. In a multivariable
      logistic regression model, retinopathy was associated with longer diabetes
      duration (odds ratio, OR 1.07, 95% CI 1.03-1.11), insulin use (OR 2.14, 95% CI
      1.19-3.85), nonfasting glucose (OR 1.07, 95% CI 1.00-1.15) and microalbuminuria
      (OR 1.89, 95% CI 1.28-2.81). Sub-group analyses showed association between
      retinopathy and even low levels of microalbuminuria (1.16 mg/mmol). CONCLUSION:
      The findings suggest that low levels of microalbuminuria may be a useful risk
      predictor for identifying individuals with diabetes at high risk of retinopathy.
      The study confirms previous findings that insulin use, longer diabetes duration
      and higher levels of blood glucose are associated with retinopathy in persons
      with diabetes. The prevalence of diabetic retinopathy was similar as reported in
      other studies.

PMID- 22994367
TI  - House dust mite allergic airway inflammation facilitates neosensitization to
      inhaled allergen in mice.
AB  - BACKGROUND: The mechanism by which many monosensitized allergic individuals
      progress to polysensitization over time remains to be elucidated. Mouse models
      have contributed greatly to the understanding of sensitization to inhaled
      allergens in healthy airways but hardly any studies have addressed sensitization
      during established allergy. We hypothesized that an allergic inflammatory milieu
      might facilitate sensitization to inhaled allergens by the presence of mature
      dendritic cells (DCs) and IL-4. METHODS: Mice with house dust mite (HDM)-induced
      allergic airway inflammation received a single intratracheal dose of ovalbumin
      (OVA), 2 days after the last HDM exposure. Ten days later, sensitization was
      assessed by rechallenge with OVA. We evaluated the following factors for their
      importance in neosensitization: (1) maturation and recruitment of DCs to the
      airways, (2) dependency on DCs using CD11cDTR conditional knockout mice, (3)
      presence of ongoing airway inflammation by comparing sensitization at day 2 and
      day 14 after the last HDM exposure and (4) dependency on IL-4 by treatment with
      blocking antibodies. RESULTS: House dust mite -induced inflammation facilitated
      neosensitization to OVA. HDM-induced inflammation increased the number of airway
      DCs with a mature phenotype but a DC reduction of 93% did not inhibit
      sensitization. Neosensitization to OVA was dependent on ongoing inflammation and
      in particular on IL-4. CONCLUSIONS: These findings show that HDM-induced allergic
      airway inflammation facilitates neosensitization to a second inhaled allergen in
      an IL-4-dependent manner and provide insight into the underlying mechanism of the
      frequently observed progression to polysensitization in HDM-monosensitized
      individuals.

PMID- 22994369
TI  - Mammaglobin 1: not only a breast-specific and tumour-specific marker, but also a
      hormone-responsive endometrial protein.
AB  - AIMS: The secretoglobin mammaglobin 1 (MGB1) is strongly expressed in breast
      tumours, and is therefore used to detect breast cancer metastases, although it
      has also been detected in other tissues. The aim of this study was to examine
      MGB1 expression and its hormonal regulation in human endometrium to further
      investigate the use of MGB1 as a marker molecule. METHODS AND RESULTS:
      Mammaglobin 1 expression was assessed immunohistochemically in endometrial
      samples from 60 normal fertile patients throughout the menstrual cycle, in 49
      endometriotic tissue samples, in 15 endometrial adenocarcinomas, and in 36 breast
      carcinomas. In addition, 25 endometrial samples were analysed by western blot and
      quantitative real-time reverse transcription polymerase chain reaction. To prove
      hormonal regulation, primary endometrial epithelial cells were cultured with
      17beta-oestradiol and promegestone. MGB1 was detected in human endometrial
      tissue, with peak expression during the luteal phase, in 31% of endometriotic
      samples, in 53% of endometrial adenocarcinomas, and in 64% of breast carcinomas.
      MGB1 mRNA expression was increased in vitro by hormonal treatment. CONCLUSIONS:
      Our data show that MGB1 expression is not restricted to normal and malignant
      breast tissue. Besides its documented occurrence in endometriotic and malignant
      endometrial tissues, MGB1 is also expressed in normal human endometrium, and such
      expression is controlled by steroid hormones.

PMID- 22994370
TI  - Highly flexible molecule "Chameleon": reversible thermochromism and phase
      transitions in solid copper(II) diiminate Cu[CF3-C(NH)-CF?C(NH)-CF3]2.
AB  - Three thermochromic phases (alpha, green; beta, red; gamma, yellow) and six
      polymorphic modifications (alpha(1), monoclinic, P2(1)/n, Z = 2; beta(1),
      monoclinic, P2(1)/c, Z = 4; beta(2), triclinic, P1[overline], Z = 4; beta(3),
      monoclinic, P2(1)/n, Z = 4; gamma(1) and gamma(2), tetragonal, P4(2)/n, Z = 4)
      have been found and structurally characterized for copper(II) diiminate Cu[CF(3)
      C(NH)-CF?C(NH)-CF(3)](2) (1). The alpha phase is stable under normal conditions,
      whereas the high-temperature beta and gamma phases are metastable at room
      temperature and transform slowly into the more stable alpha phase over several
      days or even weeks. X-ray diffraction study revealed that the title molecules
      adopt different conformations in the alpha, beta, and gamma phases, namely,
      staircase-like, twisted, and planar, respectively. The investigation of the
      alpha, beta, and gamma phases by differential scanning calorimetry showed that
      the three endothermic peaks in the range 283, 360, and 438 K are present on their
      thermograms upon heating/cooling. The two peaks at 283 and 360 K correspond to
      the solid-solid phase transitions, and the high-temperature peak at 438 K belongs
      to the melting process of 1. The temperature and thermal effect of all the
      observed transitions depend on the prehistory of the crystalline sample obtained.
      A reversible thermochromic single-crystal-to-single-crystal alpha(1)<--> beta(1)
      phase transition occurring within a temperature interval of 353-358 K can be
      directly observed using a CCD video camera of the X-ray diffractometer. A series
      of other solid-solid alpha(1)->gamma(1), beta(2)->gamma(1), beta(3)->gamma(1),
      and gamma(1)<-->gamma(2) phase transitions can be triggered in 1 by temperature.
      It has been suggested that, under equilibrium conditions, the alpha(1)->gamma(1)
      and beta(2)->gamma(1) phase transitions should proceed stepwise through the
      alpha(1)->beta(1)->beta(2)->beta(3)->gamma(1) and beta(2)->beta(3)->gamma(1)
      stages, respectively. The mechanism of the phase transitions is discussed on the
      basis of experimental and theoretical data.

PMID- 22994368
TI  - Acute and chronic antiparkinsonian effects of the novel nociceptin/orphanin FQ
      receptor antagonist NiK-21273 in comparison with SB-612111.
AB  - BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor
      antagonists have been proposed as a novel therapeutic approach to Parkinson's
      disease. Main limitations of previous studies were the use of structurally
      similar compounds and the evaluation of their acute effects only. We report here
      on the acute and long-term antiparkinsonian effects of the novel compound 2-[3-[4
      (2-chloro-6-fluoro-phenyl)-piperidin-1-ylmethyl]-2-(morpholine-4-carbonyl)-indol
      1-yl]-acetamide (NiK-21273) in comparison with the potent and selective NOP
      receptor antagonist SB-612111. EXPERIMENTAL APPROACH: Basic pharmacological
      properties of NiK-21273 were studied in cell lines and isolated tissues (mouse
      and rat vas deferens). Antiparkinsonian effects were studied in reserpinized mice
      and 6-hydroxydopamine hemilesioned rats under both acute and chronic
      administration protocols. KEY RESULTS: In vitro, NiK-21273 behaved as a potent
      (pA(2) 7.7) and selective NOP receptor antagonist. In vivo, it reduced
      hypokinesia in reserpinized mice at 0.1 and 1 but not 10 mg.kg(-1), whereas SB
      612111 (0.01-1 mg.kg(-1)) provided a dose-dependent antiparkinsonian effect. NiK
      21273 ameliorated motor performance in 6-hydroxydopamine hemilesioned rats at 0.5
      and 5 but not 15 mg.kg(-1). SB-612111 replicated these effects in the 0.01-1
      mg.kg(-1) range without loss of efficacy. Both antagonists synergized with L-DOPA
      at subthreshold doses. Chronic administration of NiK-21273 provided delayed
      improvement in baseline activity at 0.5 and 1.5 mg.kg(-1), although tolerance to
      the higher dose was observed. Conversely, SB-612111 (1 mg.kg(-1)) maintained its
      effects over time without modifying baseline activity. CONCLUSIONS AND
      IMPLICATIONS: NOP receptor antagonists provide motor benefit in parkinsonism
      models although the 'therapeutic' window and long-term effects may vary between
      compounds.

PMID- 22994371
TI  - The complete mitochondrial DNA sequence of Crotalus horridus (timber
      rattlesnake).
AB  - The complete mitogenome of the timber rattlesnake (Crotalus horridus) was
      completed using Sanger sequencing. It is 17,260 bp with 13 protein-coding genes,
      21 tRNAs, two rRNAs and two control regions. Gene synteny is consistent with
      other snakes with the exception of a missing redundant tRNA (Ser) . This
      mitogenome should prove to be a useful addition of a well-known member of the
      Viperidae snake family.

PMID- 22994372
TI  - Atmospheric chemistry of 2-aminoethanol (MEA): reaction of the NH2(*)CHCH2OH
      radical with O2.
AB  - The alkanolamine 2-aminoethanol (NH(2)CH(2)CH(2)OH), otherwise known as
      monoethanolamine (MEA), is a widely used solvent for carbon capture, yet
      relatively little is known about its atmospheric chemistry. The hydroxyl radical
      initiated oxidation of MEA is thought to predominantly form the alpha-aminoalkyl
      radical NH(2)(*)CHCH(2)OH, which will subsequently react with O(2) in the
      atmosphere to produce a peroxyl radical. We have investigated the reaction of
      O(2) with the NH(2)(*)CHCH(2)OH radical using quantum chemical calculations and
      master equation kinetic modeling. This reaction is found to proceed predominantly
      via a chemically activated mechanism under tropospheric conditions to directly
      produce the imine 2-iminoethanol (NH?CHCH(2)OH) + HO(2)(*), with lesser amounts
      of the collisionally deactivated peroxyl radical NH(2)CH(O(2)(*))CH(2)OH. By
      largely bypassing a peroxyl radical intermediate, this process avoids ozone
      promoting conversion of NO to NO(2) and makes the oxidation of MEA to 2
      iminoethanol HO(x)-neutral overall. The imine product of MEA oxidation is
      proposed as an important intermediate in the formation of aerosols via uptake to
      water droplets and subsequent hydrolysis to ammonia and glycolaldehyde.

PMID- 22994373
TI  - The changing landscape of america's health care system and the value of emergency
      medicine.
AB  - The Patient Protection and Affordable Care Act (ACA), passed in 2010, has
      important implications for emergency physicians (EPs). In addition to
      dramatically reducing the number of uninsured in the United States, this
      comprehensive health care reform legislation seeks to curb the escalating costs
      of health care delivery, optimize resource utilization, eliminate waste, and
      improve the quality of service delivered by the health care system. At the annual
      Association of American Medical Colleges (AAMC) meeting on November 5, 2011, an
      expert panel from public health, emergency medicine, and health services research
      was convened by the Association of Academic Chairs of Emergency Medicine (AACEM)
      and the Society for Academic Emergency Medicine (SAEM) to discuss possible future
      models for the emergency care system and academic emergency medicine in the era
      of the ACA.

PMID- 22994374
TI  - Transportation into narrative worlds: implications for entertainment media
      influences on tobacco use.
AB  - AIMS: A growing body of research suggests that smoking portrayals in movies
      influence adolescent tobacco use. However, the mechanism for this influence
      remains unclear. The aim of this paper is to provide an overview of research on
      narrative transportation theory, particularly as applied to movies and smoking.
      We propose that this theory can provide a valuable framework for guiding research
      on the role of entertainment media in smoking and other addictive behaviors.
      METHODS: We review empirical work on transportation theory and highlight the
      psychological mechanisms underlying transportation effects. 'Transportation into
      narrative worlds' refers to cognitive, emotional and imagery engagement into a
      narrative (including movies and entertainment media). We link this work with
      research on the effects of movie smoking. RESULTS: Research suggests that
      individuals who are more highly transported into narratives show greater
      attitude, belief and behavior change. Transportation effects work through
      reducing counterarguing, creating connections (identification and liking) with
      characters and increasing perceptions of realism and emotional involvement. We
      propose several future directions and research challenges for applying a
      transportation framework to the issue of entertainment media effects on smoking
      and tobacco disparities. Understanding factors contributing to transportation may
      provide a more nuanced view of who will be affected by movie smoking, and
      understanding the psychological processes underlying narrative persuasion may
      guide intervention efforts. CONCLUSIONS: Narrative transportation theory suggests
      that individuals' cognitive, emotional and imagery immersion in a narrative is a
      key mechanism of attitude, belief and behavior change. This theory provides a
      potentially generative and psychologically grounded framework for increasing
      knowledge about the boundary conditions and processes underlying the effects of
      entertainment media on tobacco use.

PMID- 22994375
TI  - CSF biomarking for diagnosis and treatment assessment in neurodegeneration.

PMID- 22994376
TI  - Let's talk about sex: reflections on conversations about love and sexuality in
      Kumasi and Endwa, Ghana.
AB  - This paper recounts and reflects on conversations about love and sexuality
      conducted with young people in Kumasi and Endwa, Ghana. It examines the settings
      of these conversations - in a kinship-based household, secondary schools and
      Pentecostal churches - and explores young people's reticence to talk about such
      matters in the light of intergenerational respect. Analysing young people's
      strategies of silence and provocative speech, the paper shows that,
      paradoxically, schools and churches provide institutionalised spaces for young
      people's subversive outspokenness that contrasts with the ethical codex of
      decency as the expression of hierarchical relations.

PMID- 22994377
TI  - Patient accounts of diagnostic testing for familial hypercholesterolaemia:
      comparing responses to genetic and non-genetic testing methods.
AB  - BACKGROUND: Continuing developments in genetic testing technology together with
      research revealing gene-disease associations have brought closer the potential
      for genetic screening of populations. A major concern, as with any screening
      programme, is the response of the patient to the findings of screening, whether
      the outcome is positive or negative. Such concern is heightened for genetic
      testing, which it is feared may elicit stronger reactions than non-genetic
      testing. METHODS: This paper draws on thematic analysis of 113 semi-structured
      interviews with 39 patients being tested for familial hypercholesterolaemia (FH),
      an inherited predisposition to early-onset heart disease. It examines the impact
      of disease risk assessments based on both genetic and non-genetic information, or
      solely non-genetic information. RESULTS: The impact of diagnostic testing did not
      seem to vary according to whether or not genetic information was used. More
      generally, being given a positive or negative diagnosis of FH had minimal
      discernible impact on people's lives as they maintained the continuity of their
      beliefs and behaviour. CONCLUSIONS: The results suggest that concerns about the
      use of genetic testing in this context are unfounded, a conclusion that echoes
      findings from studies in this and other health contexts.

PMID- 22994378
TI  - Elderly patients' experiences using adaptive conjoint analysis software as a
      decision aid for osteoarthritis of the knee.
AB  - BACKGROUND: Decision making in knee osteoarthritis, with many treatment options,
      challenges patients and physicians alike. Unfortunately, physicians cannot
      describe in detail each treatment's benefits and risks. One promising adjunct to
      decision making in osteoarthritis is adaptive conjoint analysis (ACA). OBJECTIVE:
      To obtain insight into the experiences of elderly patients who use adaptive
      conjoint analysis to explore treatment options for their osteoarthritis. DESIGN:
      Participants, all 65 and older, completed an ACA decision aid exploring their
      preferences with regard to the underlying attributes of osteoarthritis
      interventions. We used focus groups to obtain insight into their experiences
      using this software. RESULTS: Content analysis distributed our participants'
      concerns into five areas. The predicted preferred treatment usually agreed with
      the individual's preference, but our participants experienced difficulty in four
      other domains: the choices presented by the software were sometimes confusing,
      the treatments presented were not the treatments of most interest, the
      researchers' claims about treatment characteristics were unpersuasive and
      cumulative overload sometimes developed. CONCLUSION: Adaptive conjoint analysis
      presented special challenges to our elderly participants; we believe that their
      relatively low level of computer comfort was a significant contributor to these
      problems. We suggest that other researchers choose the software's treatments and
      present the treatment attributes with care. The next and equally vital step is to
      educate participants about what to expect, including the limitations in choice
      and apparent arbitrariness of the trade-offs presented by the software. Providing
      participants with a sample ACA task before undertaking the study task may further
      improve participant understanding and engagement.

PMID- 22994379
TI  - An investigational ovarian stimulation protocol increased significantly the
      psychological burden in women with premature ovarian failure.
AB  - OBJECTIVE: To assess the psychological impact (Hospital Anxiety and Depression
      Scale) of an investigational ovarian stimulation protocol in women with premature
      ovarian failure (POF). DESIGN: Prospective longitudinal study. POPULATION: Ten
      women with POF. METHODS: Women with idiopathic POF were placed on three
      consecutive treatment cycles consisting of gonadotropin ovarian stimulation after
      estrogen priming, gonadotropin-releasing hormone agonist pituitary
      desensitization, and corticosteroid immune suppression. RESULTS: Median anxiety
      and depression scores increased significantly from baseline following three
      consecutive treatment cycles from 4.0 (range 2.0-8.0) to 11.0 (range 10.0-14.0)
      (p-value 0.041) and from 1.5 (range 0-6.0) to 9.0 (range 7.0-10.0) (p-value
      0.039), respectively. There were nine "probable" anxiety (90%) and three
      "probable" depression (30%) cases on the final treatment cycle compared with none
      (0%) on baseline (p-value 0.004 and 0.250, respectively). CONCLUSIONS: The use of
      investigational ovarian stimulation protocols in women with idiopathic POF was
      associated with excessive psychological strain. Women with POF should be
      cautioned against the potentially harmful aspect of similar treatments of
      unproven benefit.

PMID- 22994380
TI  - Diagnostic accuracy of liquid-based endometrial cytology in the evaluation of
      endometrial pathology in postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to compare liquid-based endometrial cytology
      with hysteroscopy and endometrial biopsy regarding its diagnostic accuracy in a
      series of postmenopausal women with abnormal uterine bleeding (AUB) or
      asymptomatic women with thickened endometrium assessed by transvaginal ultrasound
      as a screening procedure. METHODS:   Inclusion criteria were: menopausal status;
      the presence of AUB and/or thickened endometrium assessed by ultrasound (cut-off
      4 mm); a normal Papanicolaou (Pap) smear; and no adnexal pathology at ultrasound.
      Exclusion criteria were: previous endometrial pathology; and previous operative
      hysteroscopy. Of 768 postmenopausal women referred to our general gynaecology
      clinics, 121 fulfilled the inclusion criteria and were recruited to the trial.
      Twenty-one refused to participate. Cytological sampling was carried out by
      brushing the uterine cavity using the Endoflower device with no cervical dilation
      and the vial was processed using a ThinPrep(r) 2000 automated slide processor.
      The slides were stained using a Pap method. RESULTS:   In 98 cases with
      histological biopsies, endometrial cytology detected five cases of endometrial
      carcinoma, 10 of atypical hyperplasia and 47 of non-atypical hyperplasia; 36
      cases were negative. In two cases cytology was inadequate because of uterine
      cervical stenosis. Taking atypical hyperplasia or worse as a positive test and
      outcome, the diagnostic accuracy of the endometrial cytology was 93.5%, with a
      sensitivity of 92% and specificity of 95%, a positive predictive value of 73% and
      a negative predictive value of 99%. All the carcinomas were detected by cytology.
      Only 42% of women with a positive diagnosis were symptomatic. The cytological
      sampling was well tolerated by all patients. No complication was registered.
      CONCLUSIONS:  Liquid-based endometrial cytology can be considered an useful
      diagnostic method in the detection of endometrial pathology as a first-line
      approach, particularly if associated with transvaginal ultrasound.

PMID- 22994381
TI  - Experimental and theoretical investigation of 1J(CC) and (n)J(CC) coupling
      constants in strychnine.
AB  - A relatively unexplored and unexploited means of establishing molecular
      structure, stereochemistry, and probing vicinal bond angles is through the use of
      long-range (13)C-(13)C coupling constants. The measurement of these
      multifunctional, diagnostic (3)J(CC) couplings has not been reported on sample
      amounts viable for the practicing organic chemist. A generalized protocol for the
      measurement of (1)J(CC) and (3)J(CC) couplings using a 4.6 mg sample of
      strychnine as a model compound is described, and the utility of DFT calculations
      for the prediction of these useful molecular descriptors and the congruence of
      the calculated and experimental data is demonstrated.

PMID- 22994382
TI  - Appropriate use of silver dressings in wounds: international consensus document.

PMID- 22994383
TI  - A new flavan-3-ol lactone and other constituents from Euonymus alatus with
      inhibitory activities on alpha-glucosidase and differentiation of 3T3-L1 cells.
AB  - Bioassay-guided fractionation, based on inhibition of alpha-glucosidase, of
      Euonymus alatus led to the isolation of a new compound, catechin lactone A (7),
      and seven known compounds (1-6 and 8). Their structures were established on the
      basis of extensive 1D- and 2D-NMR experiments. The absolute configurations of
      compound 7 have been determined using vibrational circular dichroism
      spectroscopy. All these compounds were evaluated for their inhibition activities
      on alpha-glucosidase and differentiation of 3T3-L1 cells. Compounds 1, 3-5, 7 and
      8 showed potent yeast alpha-glucosidase inhibition with IC50 values of 119.1,
      39.6, 31.6, 23.0, 71.8 and 102.5 uM, respectively; compounds 3-5, 7 and 8 can
      remarkably inhibit the differentiation of 3T3-L1 pre-adipocytes. This is the
      first report about alpha-glucosidase and 3T3-L1 inhibitory activities of
      compounds 3, 7 and 8.

PMID- 22994385
TI  - Increasing prevalence of asthma, allergic rhinoconjunctivitis and eczema among
      schoolchildren: three surveys during the period 1985-2008.
AB  - AIM: The prevalence of asthma, allergic rhinoconjunctivitis (AR) and eczema among
      children has increased worldwide in the last four decades, but recent studies
      disagree as to whether the prevalence is continuing to rise or is levelling off
      or declining. The aim of this study was to assess time trends in a subarctic
      population. METHODS: A cross-sectional, questionnaire-based survey was carried
      out in 2008 among children aged 7-14 years in randomly selected schools in
      Nordland County, Norway (n = 4150). The results are compared with results from
      identical studies in 1985 (n = 4870) and 1995 (n = 4456). RESULTS: The main
      findings were an increasing prevalence of asthma ever (7.3% in 1985 to 17.6% in
      2008, p for trend < 0.001) and AR ever (15.9% in 1985 to 24.5% in 2008, p for
      trend < 0.001), while the prevalence of eczema ever, after an increase between
      1985 and 1995, remained unchanged in the last time period. The prevalence of
      current disease doubled and trebled between 1995 and 2008 for all three diseases.
      CONCLUSION: A repeated cross-sectional survey between 1985 and 2008 documented an
      increasing prevalence of asthma ever and AR ever among schoolchildren (7-14
      years), together with a considerably increase in current asthma, AR and eczema
      between 1995 and 2008.

PMID- 22994384
TI  - Fasudil ameliorates disease progression in experimental autoimmune
      encephalomyelitis, acting possibly through antiinflammatory effect.
AB  - AIM: The purpose of this investigation was to further explore the mechanism(s)
      underlying the amelioration in EAE caused by Fasudil, particularly focusing on
      anti-inflammatory effect. METHODS: We induced a chronic-progressive experimental
      autoimmune encephalomyelitis (EAE) in B6 mice immunized with myelin
      oligodendrocyte glycoprotein(35-55)  and performed Fasudil intervention in early
      and late stages of the disease. RESULTS: The administration of Fasudil (40 mg/kg,
      i.p) had a therapeutic effect in delaying the onset and ameliorating the severity
      of EAE, accompanied by the improvement in myelination and the decrease in
      inflammatory cells in spinal cords. Fasudil inhibited TLR-4, p-NF-kB/p65, and
      inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) and enhanced IL-10
      production in spinal cords. The ratio of arginase/iNOS was enhanced mainly in the
      spinal cords of EAE mice treated with Fasudil, reflecting a shift toward the M2
      (antiinflammation) macrophage/microglia phenotype. The administration of Fasudil
      also induced the upregulation of CB2 receptor in spinal cords, but did not
      significantly trigger CB1 receptor. Levels of neurotrophic factors NGF, BDNF, and
      GDNF in the CNS were not altered by Fasudil. CONCLUSION: Fasudil ameliorates
      disease progression in EAE, acting possibly through antiinflammatory pathway.

PMID- 22994386
TI  - Sensitization to acid-hydrolyzed wheat protein by transdermal administration to
      BALB/c mice, and comparison with gluten.
AB  - BACKGROUND: An increasing number of studies have shown that hydrolyzed wheat
      protein (HWP) can induce IgE-mediated hypersensitivity by skin contact and/or
      food ingestion. However, there has been no study of the sensitizing potential of
      HWP. In this study, the possibility of transdermal pathway for sensitization to
      acid-HWP (HWP1) was investigated using BALB/c mice, and compared with that of
      gluten. METHODS: HWP1 or gluten (500 MUg/mouse) was transdermally administered
      using patches. After three or four cycles of sensitization for 3 days/week,
      active systemic anaphylaxis (ASA) was induced by intraperitoneal injection of the
      antigen, and rectal temperatures, scores of anaphylactic responses, and plasma
      histamine levels were determined. Because HWP1 was included in facial soap in
      Japan, the effect of detergent on the sensitizing potential was also
      investigated. RESULTS: Transdermal administration of HWP1 induced dose-dependent
      production of IgE and IgG1. After sensitization for 3 or 4 weeks, intraperitoneal
      injection of HWP1 caused ASA, leading to decreased rectal temperatures, increased
      anaphylaxis scores, and increased plasma histamine levels. In addition,
      splenocytes harvested after ASA produced IL-4, IL-5, and IL-10 by re-stimulation
      with HWP1. Transdermal exposure to gluten also induced IgE and IgG1 production,
      and intraperitoneal injection of gluten also induced ASA only in mice sensitized
      in the presence of sodium dodecyl sulfate. CONCLUSIONS: Transdermal exposure to
      HWP1 is sufficient to activate key immune pathways necessary for sensitizing mice
      for immediate hypersensitivity reactions. This study shows that HWP has a
      sensitizing potential as well as gluten, whereas its allergenicity may be
      different from that of gluten.

PMID- 22994387
TI  - Editorial Comment to renal pelvic villous adenoma presented with mucusuria:
      report of a case and literature review.

PMID- 22994388
TI  - Vesicle-to-cytosol transport of disulfide-linked cargo mediated by an amphipathic
      cell-penetrating peptide.
AB  - The effect of linker stability on the intracellular localization and apoptotic
      activity of cytochrome c (Cyt c) conjugated to an amphipathic cell-penetrating
      peptide (CPP), model amphipathic peptide (MAP), was tested in HeLa cells. While
      conjugates linked with a stable thioether cross-linkage were only found in the
      vesicular compartment, a portion of the conjugate linked with a reducible
      disulfide bond was also detected in the cytosol. The apoptotic function of the
      reducible and non-reducible Cyt c-MAP conjugates was also evaluated
      quantitatively using the caspase 3 and annexin V/propidium iodide detection
      assays in the presence of a proteasome inhibitor used to inhibit cytosolic Cyt c
      degradation. Analysis for early phase apoptosis revealed that linker stability
      was important for biological activity. Only the reducible disulfide-linked Cyt c
      MAP conjugate, and not free Cyt c or thioether-linked Cyt c-MAP, initiated
      apoptosis in proteasome-inhibited cells which correlated with the cytosolic
      localization profiles of the proteins. The co-treatment of disulfide-linked Cyt c
      MAP with a disulfide reduction inhibitor decreased the amount of Cyt c delivered
      to the cytosol, which correlated with a lack of apoptotic activity. These
      findings indicated the presence of a vesicle-to-cytosolic delivery process for
      disulfide-linked MAP conjugates, which can be used to improve CPP-based drug
      delivery systems transporting cargo to cytosolic sites.

PMID- 22994389
TI  - Enantioselective total synthesis of the mexicanolides: khayasin, proceranolide,
      and mexicanolide.
AB  - The enantioselective total synthesis of the limonoids khayasin, proceranolide and
      mexicanolide was achieved via a convergent strategy utilizing a tactic aimed at
      incorporating natural products as advanced intermediates. This extended
      biomimetically inspired approach additionally achieved the enantioselective total
      synthesis of the intermediates azedaralide and cipadonoid B.

PMID- 22994390
TI  - Incidence and prognosis of persistent pain induced by venipuncture for blood
      sampling: an observational study over a 5-year period.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and prognosis
      of persistent and neuropathic pain induced by venipuncture for blood sampling in
      clinical practice. DESIGN & SETTING: We investigated the incidence of persistent
      and neuropathic pain after venipuncture for blood sampling and evaluated the
      prognosis of patients with neuropathic pain at Nihon University Itabashi
      Hospital, Japan, based on an observational study. SUBJECTS: Outpatients who
      required venipuncture for blood sampling at the laboratory room of Nihon
      University Itabashi Hospital between 2004 and 2008 were included as study
      subjects. RESULTS: In the present study, of the 587,551 venipunctures performed
      at our hospital between 2004 and 2008, the incidences of persistent and
      neuropathic pain after venipuncture were 1 in every 4,418 venipunctures
      (133/587,551) and 1 in every 30,923 venipunctures (19/587,551), respectively. All
      the 19 patients who were identified as having neuropathic pain recovered
      completely. CONCLUSIONS: We demonstrated that the incidence of persistent pain
      after venipuncture for blood sampling is low and that its prognosis is good.

PMID- 22994391
TI  - Effect of overexpression of human aldehyde dehydrogenase 2 in LLC-PK1 cells on
      glyceryl trinitrate biotransformation and cGMP accumulation.
AB  - BACKGROUND AND PURPOSE: Recent studies suggest a primary role for aldehyde
      dehydrogenase 2 (ALDH2) in mediating the biotransformation of organic nitrates,
      such as glyceryl trinitrate (GTN), to the proximal activator of soluble guanylyl
      cyclase (sGC), resulting in increased cGMP accumulation and vasodilation. Our
      objective was to assess the role of ALDH2 in organic nitrate action using a cell
      culture model. EXPERIMENTAL APPROACH: Porcine renal epithelial (LLC-PK1) cells
      possess an intact NO-sGC-cGMP signaling system, and can be used as a biochemical
      model of organic nitrate action. We used a pcDNA3.1-human ALDH2 expression vector
      to establish a stably transfected cell line (PK1(ALDH2)) that overexpressed
      ALDH2, or small interfering RNA (siRNA) to deplete endogenous ALDH2, and assessed
      GTN biotransformation and GTN-induced cGMP formation. KEY RESULTS: ALDH2 activity
      in the stably transfected cells was approximately sevenfold higher than wild-type
      cells or cells stably transfected with empty vector (PK1(vector)); and protein
      expression, as assessed by immunoblot analysis, was markedly increased. In
      PK1(ALDH2), GTN biotransformation was significantly increased as a result of
      increased glyceryl-1,2-dinitrate formation compared to wild-type or PK1(vector).
      However, the incubation of PK1(ALDH2) with 1 or 10 MUM GTN did not alter GTN
      induced cGMP accumulation compared with wild-type or PK1(vector) cells.
      Furthermore, siRNA-mediated depletion of ALDH2 had no effect on GTN-induced cGMP
      formation. CONCLUSIONS AND IMPLICATIONS: In an intact cell system, neither
      overexpression nor depletion of ALDH2 affects GTN-induced cGMP formation,
      indicating that ALDH2 does not mediate the mechanism-based biotransformation of
      GTN to an activator of sGC.

PMID- 22994392
TI  - Taxon-specific C/N relative use efficiency for amino acids in an estuarine
      community.
AB  - Microbial activity plays a critical role in determining the nutrient status of an
      ecosystem (i.e. N or C limitation). While the balance of C/N assimilation has
      been measured at the whole community scale, quantitative detection of N and C
      assimilation from a single substrate at the scale of individual taxa has not been
      carried out. We recently developed Chip-SIP, a microarray and NanoSIMS-based
      method for linking microbial phylogeny and function that allows simultaneous
      measurement of (15)N and (13)C incorporation. Here, we measured the relative
      incorporation of C and N from dual-labeled substrates by individual microbial
      taxa in bottle incubations of samples collected from an estuary. Incubation times
      < 24 h were sufficient to successfully detect active microbes incorporating (15)N
      ammonium. In subsequent experiments, we used the incorporation of labeled amino
      acids (AAs) as a proxy for heterotrophic activity and showed different levels of
      incorporation among different taxonomic groups. Taxon-specific differences in the
      net incorporation of AA-derived C and N indicate that the C/N relative use
      efficiency ranged from 0.8 to 1.4, where 1 reflects stoichiometric incorporation
      of C and N. Our results revealed that microbial organic matter processing is
      affected by taxon-specific physiological diversity, both in terms of general
      activity levels and in the ratio of assimilated C/N.

PMID- 22994393
TI  - Extremely low volume, whole-body aerobic-resistance training improves aerobic
      fitness and muscular endurance in females.
AB  - The current study evaluated changes in aerobic fitness and muscular endurance
      following endurance training and very low volume, whole-body, high-intensity,
      interval-style aerobic-resistance training. Subjects' enjoyment and
      implementation intentions were also examined prior to and following training.
      Subjects (22 recreationally active females (20.3 +/- 1.4 years)) completed 4
      weeks of exercise training 4 days per week consisting of either 30 min of
      endurance treadmill training (~85% maximal heart rate; n = 7) or whole-body
      aerobic-resistance training involving one set of 8 * 20 s of a single exercise
      (burpees, jumping jacks, mountain climbers, or squat thrusts) separated by 10 s
      of rest per session (n = 7). A third group was assigned to a nontraining control
      group (n = 8). Following training, [Formula: see text]O(2peak) was increased in
      both the endurance (~7%) and interval (~8%) groups (p < 0.05), whereas muscle
      endurance was improved (p < 0.05) in the interval group (leg extensions, +40%;
      chest presses, +207%; sit-ups, +64%; push-ups, +135%; and back extensions, +75%).
      Perceived enjoyment of, and intentions to engage in, very low volume, high
      intensity, whole-body interval exercise were both increased following training (p
      < 0.05). No significant changes were observed for any variable in the control
      (nontraining) group. These data demonstrate that although improvements in
      cardiovascular fitness are induced by both endurance and extremely low volume
      interval-style training, whole-body aerobic-resistance training imparted addition
      benefit in the form of improved skeletal muscle endurance.

PMID- 22994394
TI  - Global emergency medicine: a review of the literature from 2011.
AB  - OBJECTIVES: The Global Emergency Medicine Literature Review (GEMLR) conducts an
      annual search of published and unpublished articles relevant to global emergency
      medicine (EM) to identify, review, and disseminate the most important research in
      this field to a wide audience of academics and practitioners. METHODS: This year,
      7,924 articles written in seven languages were identified by our search. These
      articles were divided up among 20 reviewers for initial screening based on their
      relevance to the field of global EM. An additional two reviewers searched the
      grey literature. A total of 206 articles were deemed appropriate by at least one
      reviewer and approved by their editor for formal scoring of their overall quality
      and importance. RESULTS: Of the 206 articles that met our predetermined inclusion
      criteria, 24 articles received scores of 17 or higher and were selected for
      formal summary and critique. Interrater reliability for our scoring system was
      good with an interclass correlation coefficient of 0.628 (95% confidence interval
      = 0.51 to 0.72). CONCLUSIONS: Compared to previous reviews, there was a
      significant increase in the number of articles that were devoted to emergency
      care in resource-limited settings, with fewer articles related to disaster and
      humanitarian response. The majority of articles that met our selection criteria
      were reviews that examined the efficacy of particular treatment regimens for
      diseases that are primarily seen in low- and middle-income countries.

PMID- 22994395
TI  - Acceleration in the care of older adults: new demands as predictors of employee
      burnout and engagement.
AB  - AIM: This paper introduces the concept of acceleration-related demands in the
      care of older adults. It examines these new demands and their relation to
      cognitive, emotional, and physical job demands and to employee well-being.
      BACKGROUND: Various changes in the healthcare systems of Western societies pose
      new demands for healthcare professionals' careers and jobs. In particular today's
      societal changes give rise to acceleration-related demands, which manifest
      themselves in work intensification and in increasing requirements to handle new
      technical equipment and to update one's job-related knowledge. It is, therefore,
      of interest to investigate the effects of these new demands on the well-being of
      employees. DESIGN: Survey. METHOD: Between March-June 2010 the survey was
      conducted among healthcare professionals involved in care of older adults in
      Austria. A total of 1498 employees provided data on cognitive, emotional, and
      physical job demands and on acceleration-related demands. The outcome variables
      were the core dimensions of burnout (emotional exhaustion and depersonalization)
      and engagement (vigour and dedication). RESULTS: Hierarchical regression analyses
      show that acceleration-related demands explain additional variance for
      exhaustion, depersonalization, vigour, and dedication when controlling for
      cognitive, emotional, and physical demands. Furthermore, acceleration-related
      demands associated with increasing requirements to update one's knowledge are
      related to positive outcomes (vigour and dedication). Acceleration-related
      demands associated with an increasing work pace are related to negative outcomes
      such as emotional exhaustion. CONCLUSION: Results illustrate that new demands
      resulting from social acceleration generate potential challenges for on-the-job
      learning and potential risks to employees' health and well-being.

PMID- 22994396
TI  - Population impact of reimbursement for smoking cessation: a natural experiment in
      The Netherlands.
AB  - AIMS: To report on the impact of financial reimbursement of pharmacotherapy for
      smoking cessation in combination with behavioural support on the number of
      enrollees to proactive counselling in the Dutch national quitline. DESIGN:
      Descriptive time-series analysis was used to compare quitline enrolment in 2010
      and 2012 (no reimbursement) with 2011 (reimbursement). SETTINGS: National smoking
      cessation quitline. PARTICIPANTS: Smokers signing up for proactive counselling.
      MEASUREMENTS: Treatment enrolment data recorded by the quitline as part of usual
      care from 2010, 2011 and 2012 (until May). FINDINGS: In 2010, a total of 848
      smokers started treatment. In 2011, 9091 smokers enrolled. In 2012, the number of
      enrollees dropped dramatically, even below the 2010 level. In addition, the
      proportion of smokers in the population dropped from 27.2% in 2010 to 24.7% in
      2011. CONCLUSIONS: The introduction of a national reimbursement system in the
      Netherlands was associated with a more than 10-fold increase in telephone
      counselling for smoking cessation and suggests that reimbursement for smoking
      cessation contributed to improvements in public health.

PMID- 22994397
TI  - Structural features of small benzene clusters (C6H6)n (n <= 30) as investigated
      with the all-atom OPLS potential.
AB  - The structures of the simplest aromatic clusters, benzene clusters (C(6)H(6))(n),
      are not well elucidated. In the present study, benzene clusters (C(6)H(6))(n) (n
      <= 30) were investigated with the all-atom optimized parameters for liquid
      simulation (OPLS) potential. The global minima and low-lying minima of the
      benzene clusters were searched with the heuristic method combined with
      geometrical perturbations. The structural features and growth sequence of the
      clusters were examined by carrying out local structure analyses and structural
      similarity evaluation with rotational constants. Because of the anisotropic
      interaction between the benzene molecules, the local structures consisting of 13
      molecules are considerably deviated from regular icosahedron, and the geometries
      of some of the clusters are inconsistent with the shapes constructed by the
      interior molecules. The distribution of the angle between the lines normal to two
      neighboring benzene rings is anisotropic in the clusters, whereas that in the
      liquid benzene is nearly isotropic. The geometries and energies of the low-lying
      configurations and the saddle points between them suggest that most of the
      configurations previously detected in supersonic expansions take different
      orientations for one to four neighboring molecules.

PMID- 22994399
TI  - Cannabinoid 1 receptor in fatty liver.
AB  - The role of cannabinoids in fatty liver disease has been increasingly
      acknowledged in recent years, and it has been suggested that drugs targeting
      peripheral cannabinoid receptors could have therapeutic use. Development of such
      drugs would require a good understanding of the mechanisms of fat accumulation
      caused by cannabinoid receptor activation. This review describes in detail the
      enzymatic steps that lead from the stimulation of cannabinoid 1 receptor to
      steatosis. It identifies several signaling pathways that activate sterol
      regulatory element-binding protein 1c (SREBP-1c), the key transcription factor
      causing fatty liver. The downstream effects of SREBP-1c leading to increased
      fatty acid synthesis and decreased fatty acid oxidation are also described.

PMID- 22994398
TI  - Porosity and cell preseeding influence electrospun scaffold maturation and
      meniscus integration in vitro.
AB  - Electrospinning generates fibrous scaffolds ideal for engineering soft orthopedic
      tissues. By modifying the electrospinning process, scaffolds with different
      structural organization and content can be generated. For example, fibers can be
      aligned in a single direction, or the porosity of the scaffold can be modified
      through the use of multi-jet electrospinning and the removal of sacrificial
      fibers. In this work, we investigated the role of fiber alignment and scaffold
      porosity on construct maturation and integration within in vitro meniscus
      defects. Further, we explored the effect of preseeding expanded meniscus
      fibrochondrocytes (MFCs) onto the scaffold at a high density before in vitro
      repair. Our results demonstrate that highly porous electropun scaffolds integrate
      better with a native tissue and mature to a greater extent than low-porosity
      scaffolds, while scaffold alignment does not influence integration or maturation.
      The addition of expanded MFCs to scaffolds before in vitro repair improved
      integration with the native tissue, but did not influence maturation. In
      contrast, preculture of these same scaffolds for 1 month before repair decreased
      integration with the native tissue, but resulted in a more mature scaffold
      compared to implantation of cellular scaffolds or acellular scaffolds. This work
      will inform scaffold selection in future in vivo studies by identifying the ideal
      scaffold and seeding methods for meniscus tissue engineering.

PMID- 22994400
TI  - Complete mitochondrial genome of Sarcocheilichthys parvus (Cypriniformes,
      Cyprinidae).
AB  - The complete mitochondrial genome of Sarcocheilichthys parvus was first obtained.
      The genome is 16,677 bp in length with 56.36% A+T content, consisting of 13
      protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1
      noncoding control region. It has the typical vertebrate mitochondrial gene
      arrangement.

PMID- 22994401
TI  - Controlling ion-sensing specificity of N-amidothioureas: from anion-selective
      sensors to highly Zn(2+)-selective sensors by tuning electronic effects.
AB  - N-Amidothioureas bearing nitro groups showed different sensitivities to various
      anions, while those with methoxy moieties exhibited the sensitive and selective
      fluorescence turn-on property for Zn(2+) in aqueous solution and in cells. N
      Amidothioureas can therefore be adjusted from anion-selective sensors to Zn(2+)
      selective sensors by varying the electronic effects of their substituents.

PMID- 22994402
TI  - Lanthanide labeling of a potent protease activated receptor-2 agonist for time
      resolved fluorescence analysis.
AB  - Protease activated receptor-2 (PAR(2)) is one of four G-protein coupled receptors
      (GPCRs) that can be activated by exogenous or endogenous proteases, which cleave
      the extracellular amino-terminus to expose a tethered ligand and subsequent G
      protein signaling. Alternatively, PAR(2) can be activated by peptide or
      peptidomimetic ligands derived from the sequence of the natural tethered ligand.
      Screening of novel ligands that directly bind to PAR(2) to agonize or antagonize
      the receptor has been hindered by the lack of a sensitive, high-throughput,
      affinity binding assay. In this report, we describe the synthesis and use of a
      modified PAR(2) peptidomimetic agonist, 2-furoyl-LIGRLO
      (diethylenetriaminepentaacetic acid)-NH(2) (2-f-LIGRLO-dtpa), designed for
      lanthanide-based time-resolved fluorescence screening. We first demonstrate that
      2-f-LIGRLO-dtpa is a potent and specific PAR(2) agonist across a full spectrum of
      in vitro assays. We then show that 2-f-LIGRLO-dtpa can be utilized in an affinity
      binding assay to evaluate the ligand-receptor interactions between known high
      potency peptidomimetic agonists (2-furoyl-LIGRLO-NH(2), 2-f-LIGRLO; 2
      aminothiazol-4-yl-LIGRL-NH(2), 2-at-LIGRL; 6-aminonicotinyl-LIGRL-NH(2), 6-an
      LIGRL) and PAR(2). A separate N-terminal peptidomimetic modification (3
      indoleacetyl-LIGRL-NH(2), 3-ia-LIGRL) that does not activate PAR(2) signaling was
      used as a negative control. All three peptidomimetic agonists demonstrated
      sigmoidal competitive binding curves, with the more potent agonists (2-f-LIGRLO
      and 2-at-LIGRL) displaying increased competition. In contrast, the control
      peptide (3-ia-LIGRL) displayed limited competition for PAR(2) binding. In
      summary, we have developed a europium-containing PAR(2) agonist that can be used
      in a highly sensitive affinity binding assay to screen novel PAR(2) ligands in a
      high-throughput format. This ligand can serve as a critical tool in the screening
      and development of PAR(2) ligands.

PMID- 22994403
TI  - Pure and mixed mucinous carcinoma of the breast: fine needle aspiration cytology
      findings and review of the literature.
AB  - OBJECTIVE: Mucinous (colloid) breast carcinoma accounts for 1-6% of all breast
      cancer. It comprises pure mucinous tumours and mixed infiltrating ductal
      carcinomas with a mucinous component. As this latter mixed form has a worse
      prognosis than pure colloid carcinoma, making this diagnosis on fine needle
      aspiration cytology (FNAC) might influence the choice of treatment. METHODS:   We
      report a consecutive series of 22 cases consisting of 17 mixed and five pure
      mucinous carcinomas diagnosed by cytology and verified on histopathology.
      Patients underwent FNAC at the one-stop clinic of our institution during a 7-year
      period of time. Cytological findings were evaluated by a semi-quantitative method
      and included percentage of smear surface occupied by mucin, shape of cell
      groupings, size and outline of tumour nuclei as well as presence or absence of
      nucleolus. RESULTS:   Three of five pure mucinous carcinomas displayed at least
      two of the following features: abundant mucin, small nuclei and/or regular
      nuclear outlines. Sparse mucin, large nuclei, irregular nuclear outlines or the
      presence of nucleoli were found in 7 out of 17 mixed mucinous carcinomas but not
      in pure tumours. CONCLUSION:   Cytopathological identification of patients with
      pure mucinous carcinomas may be performed in a limited number of cases.

PMID- 22994404
TI  - Mutational spectrum and geno-phenotype correlation in Chinese families with
      hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema is a rare autosomal dominant disease, and its
      correlation between genotype and phenotype seems not to exist. So far, there are
      very few studies on Chinese population. We aimed to establish a Chinese genetic
      database of hereditary angioedema and investigated the potential correlation
      between genotype and phenotype. METHOD: All the eight exons and intron-exon
      boundaries of C1 inhibitor gene were detected in 48 unrelated families with HAE.
      The correlations between genotype and clinical parameters were evaluated by R
      statistical software. RESULTS: Thirty-five different mutations (25 of them were
      novel) and 7 SNPs (3 of them were novel) were identified. Significant difference
      was found in the level of C1 inhibitor antigen (P = 0.01793) between different
      groups of mutational types. The correlation between different groups of
      mutational types and the level of C1 inhibitor antigen (0.5047, P = 0.00027) was
      significant. The different groups of mutational types showed neither difference
      nor correlations of clinical parameters (severity score and the level of C1
      inhibitor function). CONCLUSION: It appears that nonsense, frameshift, and
      mutations on Arg466 can cause lower level of C1 inhibitor antigen than missense
      and in-frame mutations; however, it does not affect severity of symptoms.

PMID- 22994405
TI  - Somatic growth in 94 single ventricle children -- comparing systemic right and
      left ventricle patients.
AB  - AIM: We sought to compare and assess growth in single ventricle children with a
      systemic right or left ventricle in five time periods: at birth, before neonatal
      surgery, before the Glenn anastomosis and finally before and after the Fontan
      operation to 11 years of age. METHODS: We reviewed medical records on 116 single
      ventricle patients operated at Rigshospitalet, Denmark from 1987 to 2007.
      Surgical procedures, feeding route, hemodynamic variables and anthropometric
      measurements such as weight and height were registered and converted to z-scores.
      RESULTS: Ninety four single ventricle patients were included for analysis.
      Gestational age and birth weight was not significantly different between the left
      and right ventricle group. Before neonatal surgery and before the Glenn
      anastomosis, both groups showed equal growth retardation. However, a significant
      difference in catch-up growth was found before the Fontan operation. Thus,
      patients in the right ventricle group had a smaller median weight-for-age z-score
      compared with the left ventricle group in the pre-Fontan period (-1.9 and -1.6; p
      = 0.049) and in the post-Fontan period (-1.1 and -0.7; p = 0.034). CONCLUSION:
      After the Glenn anastomosis single ventricle children with a systemic left
      ventricle have better weight gain compared with children with a systemic right
      ventricle.

PMID- 22994406
TI  - The study on the relationship between IRS-1 Gly972Arg and IRS-2 Gly1057Asp
      polymorphisms and type 2 diabetes in the Kurdish ethnic group in West Iran.
AB  - An association between the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and
      type 2 diabetes mellitus (T2DM) in different ethnic groups is controversial. We
      aimed to identify the association of these polymorphisms with T2DM in the Kurdish
      ethnic group of Iran. Study groups included 336 T2DM and 341 normoglycemic
      subjects. Genotyping was determined by polymerase chain reaction-restriction
      fragment length polymorphism. Genotypic and allelic frequencies were then
      evaluated. GR and RR genotypes of IRS-1 Gly972Arg variant gave a higher risk for
      T2DM (odds ratios [OR]=1.76 and OR=3.86, respectively). IRS-1 Gly972Arg
      polymorphism was found to be significantly associated with T2DM (OR=1.63) for the
      dominant model (GG vs. GR+RR). GD genotypes of the IRS-2 Gly1057Asp variant gave
      a higher risk for T2DM (OR=1.63). The dominant model analysis of the IRS-2
      Gly1057Asp genotypes (GG vs. GD+DD) also showed an enhanced association with T2DM
      (OR=1.69). Among several combinations, GR/GD gave the highest risk for T2DM
      (OR=3.1). Other combinations were also significantly associated with T2DM,
      including, GR/GG (OR=1.86), RR/GG (OR=1.76), GG/GD (OR=1.83), and GG/DD
      (OR=2.35). HbA1c, serum triglyceride, and systolic blood pressure were higher in
      the control subjects with GR+RR genotypes compared with the GG genotype. Among
      the T2DM subjects, fasting plasma glucose was significantly lower in subjects
      with the GG genotype in relation to those with the GR+RR genotypes. Normoglycemic
      subjects carrying GD+DD genotypes of IRS-2 Gly1057Asp variation had a
      significantly higher fasting plasma glucose and total cholesterol, as compared
      with those with the GG genotype. Our findings revealed that IRS-1 Gly972Arg and
      IRS-2 Gly1057Asp polymorphisms are associated with T2DM in the Kurdish ethnic
      group.

PMID- 22994407
TI  - Cord blood C-peptide levels relate to the metabolic profile of women with and
      without gestational diabetes.
AB  - Plasma C-peptide reflects the insulin-secretory activity of pancreatic beta-cells
      which modulates fetal growth. Cord blood C-peptide levels were measured in women
      with gestational diabetes mellitus (GDM) and in women with normal glucose
      tolerance (NGT). Forty-one women underwent a 75-g oral glucose tolerance test (18
      GDM, 23 NGT). Cord blood C-peptide (p = 0.09) and glucose levels (p = 0.08) from
      newborns of GDM women tended to be higher than those from NGT women. In the
      entire group, cord blood C-peptide correlated with maternal insulin, fasting C
      peptide, insulin sensitivity, interleukin-6, weight and body mass index measured
      at screening (rho from 0.34 to 0.48, all p < 0.05) and tended to correlate with
      offspring weight (rho = 0.28, p = 0.08). Newborns of GDM women tended to have
      elevated cord blood C-peptide which correlated with maternal insulin, insulin
      sensitivity and anthropometric measures at diagnosis and with offspring
      characteristics. This suggests that insulin-secretory activity of the newborn is
      related to maternal metabolic parameters.

PMID- 22994408
TI  - Transferability and fine mapping of genome-wide associated loci for lipids in
      African Americans.
AB  - BACKGROUND: A recent, large genome-wide association study (GWAS) of European
      ancestry individuals has identified multiple genetic variants influencing serum
      lipids. Studies of the transferability of these associations to African Americans
      remain few, an important limitation given interethnic differences in serum lipids
      and the disproportionate burden of lipid-associated metabolic diseases among
      African Americans. METHODS: We attempted to evaluate the transferability of 95
      lipid-associated loci recently identified in European ancestry individuals to 887
      non-diabetic, unrelated African Americans from a population-based sample in the
      Washington, DC area. Additionally, we took advantage of the generally reduced
      linkage disequilibrium among African ancestry populations in comparison to
      European ancestry populations to fine-map replicated GWAS signals. RESULTS: We
      successfully replicated reported associations for 10 loci (CILP2/SF4, STARD3,
      LPL, CYP7A1, DOCK7/ANGPTL3, APOE, SORT1, IRS1, CETP, and UBASH3B). Through trans
      ethnic fine-mapping, we were able to reduce associated regions around 75% of the
      loci that replicated. CONCLUSIONS: Between this study and previous work in
      African Americans, 40 of the 95 loci reported in a large GWAS of European
      ancestry individuals also influence lipid levels in African Americans. While
      there is now evidence that the lipid-influencing role of a number of genetic
      variants is observed in both European and African ancestry populations, the still
      considerable lack of concordance highlights the importance of continued ancestry
      specific studies to elucidate the genetic underpinnings of these traits.

PMID- 22994409
TI  - Degradation of ascorbic acid in ethanolic solutions.
AB  - Ascorbic acid occurs naturally in many wine-making fruits. The industry also uses
      ascorbic acid as an antioxidant and color stabilizer in the making of alcoholic
      beverages including white wine, wine cooler, alcopop, and fruit liqueur. However,
      the degradation of ascorbic acid itself may cause browning and the deterioration
      of color quality. This study was aimed to monitor the degradation of ascorbic
      acid, the formation of degradation products, and the browning in storage of
      ascorbic acid containing 0-40% (v/v) ethanolic solutions buffered at pH 3.2 as
      models of alcoholic beverages. The results show that ascorbic acid degradation in
      the ethanolic solutions during storage follows first-order reaction, that the
      degradation and browning rates increase with the increase of ethanol
      concentration, that the activation energy for the degradation of ascorbic acid is
      in the range 10.35-23.10 (kcal/mol), that 3-hydroxy-2-pyrone is an indicator and
      a major product of ascorbic acid degradation, and that aerobic degradation
      pathway dominants over anaerobic pathway in ascorbic acid degradation in
      ethanolic solutions.

PMID- 22994410
TI  - The effect of a Spanish virtual pain coach for older adults: a pilot study.
AB  - OBJECTIVE: To pilot test the effects of a virtual pain coach on ambulatory
      Spanish-speaking older adults with pain from osteoarthritis. METHODS: A
      randomized, controlled design was used. Eighteen Spanish-speaking older adults
      were randomly assigned to the virtual pain coach and pain communication education
      group, or to the pain communication education-only group. All participants viewed
      the pain communication videotape. Participants in the virtual pain coach group
      practiced talking about their osteoarthritis pain with the virtual pain coach.
      Immediately after the respective intervention, participants had their ambulatory
      medical visit. Pain intensity and pain interference with activities were measured
      with the Brief Pain Inventory, and depressive symptoms were measured with the
      Beck Depression Inventory II at baseline and 1 month later. RESULTS: No
      significant group difference emerged for pain intensity, pain interference with
      activities, or depressive symptoms 1 month later. More older adults in the
      virtual pain coach group reported a change from nonuse to use of opioids at 1
      month, 50% vs 0% of the education only group, Fisher's exact test, P = 0.023.
      CONCLUSIONS:  Preliminary data indicate that the Spanish virtual pain coach might
      assist Spanish-speaking older adults to talk with their practitioner about their
      osteoarthritis pain and obtain opioid treatment changes, but that pain and
      depressive symptoms continue unchanged 1 month later. Additional refinement and
      testing is required for the Spanish-speaking virtual pain coach to determine
      acceptability and outcomes for assisting Spanish-speaking older adults to
      communicate about their pain with their primary care practitioner.

PMID- 22994411
TI  - Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug
      transport across the placenta and fetal drug exposure.
AB  - Pharmacotherapy during pregnancy is often inevitable for medical treatment of the
      mother, the fetus or both. The knowledge of drug transport across placenta is,
      therefore, an important topic to bear in mind when deciding treatment in pregnant
      women. Several drug transporters of the ABC and SLC families have been discovered
      in the placenta, such as P-glycoprotein, breast cancer resistance protein, or
      organic anion/cation transporters. It is thus evident that the passage of drugs
      across the placenta can no longer be predicted simply on the basis of their
      physical-chemical properties. Functional expression of placental drug
      transporters in the trophoblast and the possibility of drug-drug interactions
      must be considered to optimize pharmacotherapy during pregnancy. In this review
      we summarize current knowledge on the expression and function of ABC and SLC
      transporters in the trophoblast. Furthermore, we put this data into context with
      medical conditions that require maternal and/or fetal treatment during pregnancy,
      such as gestational diabetes, HIV infection, fetal arrhythmias and epilepsy.
      Proper understanding of the role of placental transporters should be of great
      interest not only to clinicians but also to pharmaceutical industry for future
      drug design and development to control the degree of fetal exposure.

PMID- 22994412
TI  - Anti-arthritic effects of clematichinenoside (AR-6) on PI3K/Akt signaling pathway
      and TNF-alpha associated with collagen-induced arthritis.
AB  - CONTEXT: Clematichinenoside (AR-6) is a triterpene saponin from an anti-arthritic
      herbal formula Wei-Ling-Xian in Chinese, which is an herbal medicine derived from
      the dried root and rhizome of Clematis chinensis Osbeck, C. hexapetala Pall., or
      C. manshurica Rupr. (Ranunculaceae). OBJECTIVE: To investigate the modulating
      effect and explored the potential mechanism of AR-6 in rheumatoid arthritis (RA),
      using collagen-induced arthritis (CIA) in a rat model. MATERIALS AND METHODS: CIA
      was evaluated by measuring body weight, paw swelling and organ index. Expression
      of TNF-alpha, PI3K and p-Akt in synovium tissue was measured by
      immunohistochemistry. Furthermore, expression of TNF-alpha mRNA, PI3K mRNA and p
      Akt mRNA was measured with RT-PCR. RESULTS: The intragastric administration of AR
      6 (32, 16 and 8 mg/kg), especially the high dose level of 32 mg/kg, significantly
      suppressed the swelling of hind paws of CIA rats (p < 0.01) and inhibited their
      body weight loss (p < 0.01). Based on histopathological observation, all AR-6
      groups showed great amelioration compared with model group. Moreover, AR-6
      significantly reduced the production of TNF-alpha, PI3K and p-Akt expression by
      immunohistochemistry (p < 0.01), and decreased TNF-alpha mRNA, PI3K mRNA and p
      Akt mRNA in CIA rat synovium (p < 0.01). DISCUSSION: Our study indicates the
      mechanism of AR-6 is associated with PI3K/Akt signaling pathway and TNF-alpha.
      CONCLUSIONS: Such characteristics relating to AR-6 curing chronic inflammation of
      CIA, may be effectively applied to the therapeutic potential in patients with
      inactive RA.

PMID- 22994413
TI  - A selective luminescent probe for the direct time-gated detection of adenosine
      triphosphate.
AB  - A molecular probe for the luminescent detection of adenosine nucleotides is
      presented. The probe, Tb-DOTAm-Phen, readily distinguishes among the three
      adenosine nucleotides in buffered aqueous conditions at neutral pH, a requirement
      for the direct monitoring of enzymatic reactions converting adenosine
      triphosphate (ATP) to adenosine diphosphate or adenosine monophosphate. The probe
      is most efficient under millimolar concentrations of ATP which are relevant to
      intracellular conditions. Moreover, the long luminescence lifetime of the probe
      readily enables time-gating experiments.

PMID- 22994415
TI  - Laparoscopic stomach-partitioning gastrojejunostomy is an effective palliative
      procedure to improve quality of life in patients with malignant gastroduodenal
      outlet obstruction.
AB  - INTRODUCTION: A patient with gastroduodenal obstruction caused by an unresectable
      gastroduodenal or periampullary cancer cannot ingest food and/or liquid. The
      patient's quality of life rapidly deteriorates, resulting in a dismal prognosis.
      Stomach-partitioning gastrojejunostomy has been previously reported, and here, we
      evaluate the laparoscopic procedure. METHODS: We performed laparoscopic stomach
      partitioning gastrojejunostomy in 18 patients with unresectable gastroduodenal or
      periampullary cancers. Data on operation time, blood loss, complications, and
      postoperative course were retrospectively collected. RESULTS: The mean operation
      time was 152 min, and conversion to open surgery was not required in any
      patients. Postoperative complications occurred in three patients (17%) and
      included cholangitis, anastomotic ulcer hemorrhage, and enterocolitis. The mean
      time to oral intake was 4.5 days, and the mean and median duration of oral intake
      were maintained for 133 and 88 days, respectively. CONCLUSION: Laparoscopic
      stomach-partitioning gastrojejunostomy is a safe and effective procedure that
      allows patients with gastroduodenal outlet obstruction to eat again and improve
      the quality of their remaining life.

PMID- 22994416
TI  - Editorial comment to epididymal cyst: not always a benign condition.

PMID- 22994414
TI  - Positive modulation of the alpha9alpha10 nicotinic cholinergic receptor by
      ascorbic acid.
AB  - BACKGROUND AND PURPOSE: The activation of alpha9alpha10 nicotinic cholinergic
      receptors (nAChRs) present at the synapse between efferent olivocochlear fibres
      and cochlear hair cells can prevent acoustic trauma. Hence, pharmacological
      potentiators of these receptors could be useful therapeutically. In this work, we
      characterize ascorbic acid as a positive modulator of recombinant alpha9alpha10
      nAChRs. EXPERIMENTAL APPROACH: ACh-evoked responses were analysed under two
      electrode voltage-clamp recordings in Xenopus laevis oocytes injected with alpha9
      and alpha10 cRNAs. KEY RESULTS: Ascorbic acid potentiated ACh responses in X.
      laevis oocytes expressing alpha9alpha10 (but not alpha4beta2 or alpha7) nAChRs,
      in a concentration-dependent manner, with an effective concentration range of 1
      30 mM. The compound did not affect the receptor's current-voltage profile nor its
      apparent affinity for ACh, but it significantly enhanced the maximal evoked
      currents (percentage of ACh maximal response, 240 +/- 20%). This effect was
      specific for the L form of reduced ascorbic acid. Substitution of the
      extracellular cysteine residues present in loop C of the ACh binding site did not
      affect the potentiation. Ascorbic acid turned into a partial agonist of
      alpha9alpha10 nAChRs bearing a point mutation at the pore domain of the channel
      (TM2 V13'T mutant). A positive allosteric mechanism of action rather than an
      antioxidant effect of ascorbic acid is proposed. CONCLUSIONS AND IMPLICATIONS:
      The present work describes one of the few agents that activates or potentiates
      alpha9alpha10 nAChRs and leads to new avenues for designing drugs with potential
      therapeutic use in inner ear disorders.

PMID- 22994417
TI  - Unconsented HIV testing in cases of occupational exposure: ethics, law, and
      policy.
AB  - Postexposure prophylaxis (PEP) has substantially reduced the risk of acquiring
      human immunodeficiency virus (HIV) after an occupational exposure; nevertheless,
      exposure to HIV remains a concern for emergency department providers. According
      to published guidelines, PEP should be taken only when source patients are HIV
      positive or have risk factors for HIV. Initiating PEP when source patients are
      uninfected puts exposed persons at risk from taking toxic drugs with no
      compensating benefit. Forgoing PEP if the source is infected results in increased
      risk of acquiring HIV. What should be done if source patients refuse HIV testing?
      Is it justifiable to test the blood of these patients over their autonomous
      objection? The authors review current law and policy and perform an ethical
      analysis to determine if laws permitting unconsented testing in cases of
      occupational exposure can be ethically justified.

PMID- 22994419
TI  - Comparative binding of disulfide-bridged PEG-Fabs.
AB  - Protein PEGylation is the most clinically validated method to improve the
      efficacy of protein-based medicines. Antibody fragments such as Fabs display
      rapid clearance from blood circulation and therefore are good candidates for
      PEGylation. We have developed PEG-bis-sulfone reagents 1 that can selectively
      alkylate both sulfurs derived from a native disulfide. Using PEG-bis-sulfone
      reagents 1, conjugation of PEG specifically targets the disulfide distal to the
      binding region of the Fab (Scheme  2 ). PEG-bis-sulfone reagents 1 (10-40 kDa)
      were used to generate the corresponding PEG-mono-sulfones 2 that underwent
      essentially quantitative conjugation to give the PEG-Fab product 4. Four Fabs
      were PEGylated: Fab(beva), Fab'(beva), Fab(rani), and Fab(trast). Proteolytic
      digestion of bevacizumab with papain gave Fab(beva), while digestion of
      bevacizumab with IdeS gave F(ab')(2-beva), which after reaction with DTT and PEG
      mono-sulfone 2 gave PEG(2)-Fab'(beva). Ranibizumab, which is a clinically used
      Fab, was directly PEGylated to give PEG-Fab(rani). Trastuzumab was
      proteolytically digested with papain, and its corresponding Fab was PEGylated to
      give PEG-Fab(trast). Purification of the PEGylated Fabs was accomplished by a
      single ion exchange chromatography step to give pure PEG-Fab products as
      determined by silver-stained SDS-PAGE. No loss of PEG was detected post
      conjugation. A comparative binding study by SPR using Biacore with low ligand
      immobilization density was conducted using (i) VEGF(165) for the bevacizumab and
      ranibizumab derived products or (ii) HER2 for the trastuzumab derived products.
      VEGF(165) is a dimeric ligand with two binding sites for bevacizumab. HER2 has
      one domain for the binding of trastuzumab. Binding studies with PEG-Fab(beva)
      indicated that the apparent affinity was 2-fold less compared to the unPEGylated
      Fab(beva). Binding properties of the PEG-Fab(beva) products appeared to be
      independent of PEG molecular weight. Site-specific conjugation of two PEG
      molecules gave PEG(2*20)-Fab'(beva), whose apparent binding affinity was similar
      to that observed for PEG-Fab(beva) derivatives. The k(d) values were similar to
      those of the unPEGylated Fab(beva); hence, once bound, PEG-Fab(beva) remained
      bound to the same degree as Fab(beva). Biacore analysis indicated that both
      Fab(rani) and PEG(20)-Fab(rani) did not dissociate from the immobilized VEGF at
      25  degrees C, but ELISA using immobilized VEGF showed 2-fold less apparent
      binding affinity for PEG(20)-Fab(rani) compared to the unPEGylated Fab(rani).
      Additionally, the apparent binding affinities for trastuzumab and Fab(trast) were
      comparable by both Biacore and ELISA. Biacore results suggested that trastuzumab
      had a slower association rate compared to Fab(trast); however, both molecules
      displayed the same apparent binding affinity. This could have been due to
      enhanced rebinding effects of trastuzumab, as it is a bivalent molecule.
      Analogous to PEG-Fab(beva) products, PEG(20)-Fab(trast) displayed 2-fold lower
      binding compared to Fab(trast) when evaluated by ELISA. The variations in the
      apparent affinity for the PEGylated Fab variants were all related to the
      differences in the association rates (k(a)) rather than the dissociation rates
      (k(d)). We have shown that (i) Fabs are well-matched for site-specific PEGylation
      with our bis-alkylation PEG reagents, (ii) PEGylated Fabs display only a 2-fold
      reduction in apparent affinity without any change in the dissociation rate, and
      (iii) the apparent binding rates and affinities remain constant as the PEG
      molecular weight is varied.

PMID- 22994418
TI  - Integration of a novel injectable nano calcium sulfate/alginate scaffold and BMP2
      gene-modified mesenchymal stem cells for bone regeneration.
AB  - The repair of craniofacial bone defects is surgically challenging due to the
      complex anatomical structure of the craniofacial skeleton. Current strategies for
      bone tissue engineering using a preformed scaffold have not resulted in the
      expected clinical regeneration due to difficulty in seeding cells into the deep
      internal space of scaffold, and the inability to inject them in minimally
      invasive surgeries. In this study, we used the osteoconductive and mechanical
      properties of nano-scale calcium sulfate (nCS) and the biocompatibility of
      alginate to develop the injectable nCS/alginate (nCS/A) paste, and characterized
      the effect of this nCS/A paste loaded with bone morphogenetic protein 2 (BMP2)
      gene-modified rat mesenchymal stem cells (MSCs) on bone and blood vessel growth.
      Our results showed that the nCS/A paste was injectable under small injection
      forces. The mechanical properties of the nCS/A paste were increased with an
      increased proportion of alginate. MSCs maintained their viability after the
      injection, and MSCs and BMP2 gene-modified MSCs in the injectable pastes remained
      viable, osteodifferentiated, and yielded high alkaline phosphatase activity. By
      testing the ability of this injectable paste and BMP2-gene-modified MSCs for the
      repair of critical-sized calvarial bone defects in a rat model, we found that
      BMP2-gene-modified MSCs in nCS/A (nCS/A+M/B2) showed robust osteogenic activity,
      which resulted in consistent bone bridging of the bone defects. The vessel
      density in nCS/A+M/B2 was significantly higher than that in the groups of blank
      control, nCS/A alone, and nCS/A mixed with MSCs (nCS/A+M). These results indicate
      that BMP2 promotes MSCs-mediated bone formation and vascularization in nCS/A
      paste. Overall, the results demonstrated that the combination of injectable nCS/A
      paste and BMP2-gene-modified MSCs is a new and effective strategy for the repair
      of bone defects.

PMID- 22994420
TI  - Motivational typologies of drinkers: do enhancement and coping drinkers form two
      distinct groups?
AB  - AIMS: This study used a person-centered approach to test whether drinking motive
      typologies could be identified. DESIGN: Longitudinal study of college students
      within the intensive multivariate prospective alcohol college-transitions
      (IMPACTS) data set. SETTING: University campus in the United States.
      PARTICIPANTS: University students (baseline n reporting alcohol motives = 2158;
      baseline age = 18.60 years old). MEASUREMENTS: The drinking motives questionnaire
      revised (DMQ-R). FINDINGS: Using Steinley & Brusco's cluster analysis approach
      [based on the theoretical ratio expected between the within sum of squares and
      the total sum of squares when the data are divided into two clusters when no
      cluster structure is present; the cut-off for the ratio is 0.25 for uniform
      (multivariate uniform) distributions and 0.36 for normal (multivariate normal)
      distributions], we examined whether there was evidence for distinct clusters of
      individuals that differed on their overall level of motives to drink. We tested
      the fit of a one-group (cluster) solution compared to multi-cluster solutions.
      Both cross-sectionally and prospectively, the data could not be partitioned into
      two or more clusters [regardless of whether the cut-off assuming a multivariate
      uniform distribution (i.e. 0.25) or the more liberal multivariate normal
      distribution (i.e., 0.36) was used]. These findings showed that enhancement and
      coping drinkers do not form two distinct groups but, rather, these motives exist
      on a continuum such that individuals who are high in one internal motive tend to
      be high in the other motive. CONCLUSIONS: Coping and enhancement drinkers do not
      form two distinct groups. Variable-centered approaches to drinking motives may be
      a better alternative to classifying all drinkers as either enhancement or coping
      drinkers for both clinical and research endeavors.

PMID- 22994421
TI  - Enhancement of ethanol production from potato-processing wastewater by
      engineering Escherichia coli using Vitreoscilla haemoglobin.
AB  - Ethanologenic Escherichia coli strain FBR5 was transformed with the Vitreoscilla
      haemoglobin (VHb) gene (vgb) in two constructs (resulting in strains TS3 and
      TS4). Strains FBR5, TS3 and TS4 were grown at two scales in LB medium
      supplemented with potato-processing wastewater hydrolysate. Aeration was varied
      by changes in the medium volume to flask volume ratio. Parameters measured
      included culture pH, cell growth, VHb levels and ethanol production. VHb
      expression in strains TS3 and TS4 was consistently correlated with increases in
      ethanol production (5-18%) under conditions of low aeration, but rarely did this
      occur with normal aeration. The increase in ethanol yields under low aeration
      conditions was the result of enhancement of ethanol produced per unit of biomass
      rather than enhancement of growth. 'VHb technology' may be a useful adjunct in
      the production of biofuels from food-processing wastewater. SIGNIFICANCE AND
      IMPACT OF STUDY: Genetic engineering using Vitreoscilla haemoglobin (VHb) has
      been shown previously to increase ethanol production by Escherichia coli from
      fermentation of the sugars in corn fibre hydrolysate. The study reported here
      demonstrates a similar VHb enhancement of ethanol production by fermentation of
      the glucose from potato waste water hydrolysate and thus extends the list of
      sugar containing waste products from which ethanol production may be enhanced by
      this strategy.

PMID- 22994422
TI  - Electronic excited state paths of Stone-Wales rearrangement in pyrene: roles of
      conical intersections.
AB  - We investigated the reaction paths of Stone-Wales rearrangement (SWR), i.e., pi/2
      rotation of two carbon atoms with respect to the midpoint of the bond, in
      graphene and carbon nanotube quantum chemically. Our particular attention is
      focused on the roles of electronic excitations and conical intersections (CIs) in
      the reaction mechanism. We used pyrene as a model system. The reaction paths were
      determined by constructing potential energy surfaces at the MS-CASPT2//SA-CASSCF
      level of theory. We found that there are no CIs involved in SWR when both of C-C
      bond cleavage and formation occur simultaneously (concerted mechanism). In
      contrast, for the reaction path with stepwise cleavage and formation of C-C
      bonds, C-C bond breaking and making processes proceed through two CIs. When SWR
      starts from the ground (S(0)) state, the concerted and stepwise paths have an
      equivalent reaction barrier DeltaE(?) (9.5-9.6 eV). For the reaction path
      starting from excited states, only the stepwise mechanism is energetically
      preferable. This path contains a nonadabatic transition between the S(1) and S(0)
      states via a CI associated with the first stage of C-C bond cleavage and has
      DeltaE(?) as large as in the S(0) paths. We confirmed that the main active
      molecular orbitals and electron configurations for the low-lying electronic
      states of larger nanocarbons are the same as those in pyrene. This result
      suggests the importance of the nonadiabatic transitions through CIs in the
      photochemical reactions in large nanocarbons.

PMID- 22994423
TI  - Development and psychometric testing of the Swedish version of the Body Awareness
      Questionnaire.
AB  - AIM: This paper is a report of the development and psychometric testing of the
      Swedish version of the Body Awareness Questionnaire to measure bodily focus of
      attention. BACKGROUND: The Body Awareness Questionnaire has been identified as an
      instrument with excellent psychometric properties within the concept of body
      awareness. It has been used in both research and clinical settings in different
      contexts. However, a validated Swedish version is not available. METHOD: A cross
      sectional design was applied for adaptation of the Body Awareness Questionnaire
      and psychometric validation. Data were collected between autumn 2009 and spring
      2011 from 120 patients diagnosed with rheumatoid arthritis, and from 120
      students. The 'concurrent think aloud' method was used in a pre-test to determine
      the usability of the questionnaire. Cronbach's alpha was used to test the
      internal consistency, and confirmatory factor analysis was performed to test the
      construct validity. RESULTS: According to the confirmatory factor analysis,
      neither the one-factor model nor the four-factor model tested in this study
      fulfilled the pre-specified criteria in accordance with the Comparative Fit
      Index, Standardized Root Mean Squared Residual and the Root Mean Square Error of
      Approximation. The value of Cronbach's alpha for the Swedish version of the Body
      Awareness Questionnaire was satisfactory. CONCLUSION: Our results indicate that
      the two models tested in this study do not provide a good fit to the observed
      data. Further refinement and testing of the Swedish version of the Body Awareness
      Questionnaire is therefore required. The concept of body awareness may be useful
      in the management of chronic disease and can be addressed in nursing.

PMID- 22994424
TI  - Environmental bacteria and childhood asthma.
AB  - BACKGROUND: We have previously found an inverse association of bacterial
      diversity with childhood asthma. It remains unclear whether certain bacteria
      account for the protective effect. METHODS: The high variability of the bacterial
      16S rRNA gene allows assessing diversity and specificity of bacterial communities
      by single-strand configuration polymorphism (SSCP). DNA was extracted from
      mattress dust samples of 489 school-age children from rural and suburban regions
      in Germany. A fragment of the bacteria-specific 16S rRNA gene was amplified by
      PCR, digested to single-strand DNA, and subjected to electrophoresis. The
      resulting band patterns reflect the underlying DNA sequences. The individual
      bands were tested for associations with asthma, hay fever, and atopy in
      quantitative and qualitative multivariable analyses. Significantly associated
      bands were isolated and sequenced. The sequences were compared to a database, and
      distinct bacteria were identified. RESULTS: Seven of 76 independent bands were
      found to be inversely associated with asthma, atopic sensitization, and hay fever
      with odds ratios ranging from 0.17 to 0.73. The bands contained the sequences of
      Acinetobacter sp., Lactobacillus spp., Neisseria spp., Staphylococcus sciuri,
      Jeotgalicoccus sp., Corynebacterium spp., and others. CONCLUSIONS: In a diverse
      microbial environment, certain bacteria may account for the protective effect on
      the development of asthma and atopy.

PMID- 22994425
TI  - The effect of genistein on the content and activity of alpha- and beta-secretase
      and protein kinase C in Abeta-injured hippocampal neurons.
AB  - Genistein (Gen), a derivative of soy isoflavone aglycone, has been shown to exert
      significant protective effect on Abeta-induced neurotoxicity and neuroinjury.
      However, its underlying mechanism remains elusive. The objective was to
      investigate the inhibitory effect of Gen on Abeta-induced neurotoxicity and to
      elucidate the underlying mechanism. Primary rat hippocampal neurons were pre
      treated with Gen for 2 hr followed by incubation with Abeta 25-35 for an
      additional 24 hr. The cell viability was assessed by MTT assay. The content and
      activity of alpha-, beta-secretase and protein kinase C (PKC) were measured, and
      the antagonistic effect of PKC inhibitor Myr was also analysed to clarify the
      molecular mechanism of Gen inhibition of Abeta-induced toxicity to hippocampal
      neurons. The results showed that pre-treatment with Gen significantly increased
      the cell viability and presented the best effect at the final concentration of
      0.375 ug/mL. Gen increases the activity of alpha-secretase but down-regulates the
      beta-secretase activity. It also enhances the expression and activity of PKC.
      Myr, a PKC inhibitor, partially blocks the activation effect of Gen. Gen exerts
      protective effect on Abeta-induced neurotoxicity via activating the PKC
      signalling pathway, which further regulates the activities of alpha- and beta
      secretase and thereby inhibits the formation and toxicity of Abeta.

PMID- 22994426
TI  - A novel acid-catalyzed O-benzylating reagent with the smallest unit of imidate
      structure.
AB  - Formal trimerization of the smallest unit of benzyl imidate leads to 2,4,6
      tris(benzyloxy)-1,3,5-triazine (TriBOT), which can be used as an acid-catalyzed O
      benzylating reagent. The reaction of various functionalized alcohols with 0.4
      equiv of TriBOT in the presence of trifluoromethanesulfonic acid afforded the
      benzyl ethers in good yields. TriBOT is an inexpensive stable crystalline solid
      with high atom economy.

PMID- 22994427
TI  - Synthesis, characterization and brain targeting potential of paclitaxel loaded
      thiamine-PPI nanoconjugates.
AB  - Brain tumor is insidious complication which is difficult to treat because of the
      poor uptake of many potentially useful antitumor drugs through the blood-brain
      barrier (BBB). Present study was aimed for developing and exploring the use of
      thiamine conjugated poly(propylene imine) (PPI) dendrimers for increased delivery
      of paclitaxel (PTX) across the BBB. PTX loaded thiamine conjugated PPI dendrimers
      (PTX-Tm-PPI) shown increased drug loading and reduced hemolytic toxicity with
      suitability for prolonged delivery of PTX during in vitro release. Ex vivo
      cytotoxicity studies of free PTX, PTX-PPI and PTX-Tm-PPI dendrimers over IMR-32
      human neuroblastoma cell line revealed higher potential of PTX-Tm-PPI
      nanoconjugate to retard tumor cell viability as compared to plain PTX or PTX-PPI.
      In vivo pharmacokinetics studies revealed significant (p < 0.05) slow clearance
      of PTX from the body via Tm-PPI nanoconjugate. Biodistribution studies confirmed
      about the targeting efficiency and higher biodistribution of Tm-PPI conjugates
      into the brain. The results concluded that the developed nanoconjugate has
      potential to deliver significantly higher amount of drug to brain tumor for
      improved therapeutic outcome.

PMID- 22994428
TI  - Association between the metabolic syndrome and its components with falls in
      community-dwelling older adults.
AB  - BACKGROUND: The metabolic syndrome and falls are both serious and common health
      problems in older adults. However, little is known about whether the metabolic
      syndrome contributes to falls. We investigated the relationship between the
      metabolic syndrome and its components with falls in community-dwelling older
      adults. METHODS: We designed and conducted a cross-sectional study. A total of
      1165 community-dwelling older adults who received a geriatric health examination,
      including interviewer-administered questionnaires and physical and biochemical
      examinations, were retrospectively enrolled from 2008 to 2010 and specifically
      asked about the history of falls in the preceding year. RESULTS: The mean age of
      the participants was 74.9 +/- 6.7 years, and 54.3% were women. The overall
      prevalence of falls and metabolic syndrome were 17.9% and 27.3%, respectively.
      Compared with those who did not fall, the participants who fell had a higher
      prevalence of the metabolic syndrome (45.7% versus 23.3%, P<0.001) and four of
      its five components, namely, abdominal obesity (51.2% versus 40.2 %, P=0.004),
      hypertriglyceridemia (32.2% versus 21.8%, P=0.001), hypertension (60.0% versus
      50.0%, P=0.009), and impaired glucose tolerance (28.4 % versus 16.0%, P<0.001).
      After adjusting for age, female sex, the Karnofsky Performance Scale, and the
      five-item Brief Symptom Rating Scale, the metabolic syndrome was a significant
      independent risk factor for falls in community-dwelling older adults (odds
      ratio=2.56, 95% confidence interval 1.86-3.51). Because falling is a
      multifactorial geriatric syndrome, many potential confounders, such as visual
      abnormalities, obesity, arthritis, and polypharmacy, were not considered in this
      study. CONCLUSION: The metabolic syndrome is an independent risk factor for falls
      in community-dwelling older adults and should be addressed with regard to
      prevention of falls.

PMID- 22994429
TI  - Nutritional management contributes to improvement in minimal hepatic
      encephalopathy and quality of life in patients with liver cirrhosis: A
      preliminary, prospective, open-label study.
AB  - AIM: Problems in patients with minimal hepatic encephalopathy (MHE) include
      episodes such as falls and deficient driving skills, without any recognition of
      neurophysiological dysfunction. Patients with MHE are also more likely to develop
      overt hepatic encephalopathy. However, there is not yet any interventional
      strategy for MHE involving nutritional management. We conducted a preliminary
      study to investigate the proportion of positive MHE and the effects of
      nutritional management on MHE. METHODS: Patients with viral liver cirrhosis and
      abnormal neuropsychological tests were included. Nutritional consultations were
      conducted periodically by a dietitian, who recommended 30-35 kcal with 1.0-1.5 g
      of protein/kg of ideal bodyweight/day. The primary end-point was to evaluate the
      proportion of patients who recovered from MHE. The secondary end-point was to
      evaluate the improvement in the patients' quality of life (QOL). RESULTS: Thirty
      two (30.1%) of 106 patients were diagnosed with MHE. Nineteen patients were
      enrolled in the study. Eleven of 19 patients became non-MHE after 4 weeks, and 13
      of 19 patients (68.4%, P < 0.001) after 8 weeks. The mental summary scores were
      significantly improved at 8 weeks (P = 0.0413). Changes in albumin levels from
      week 0 to week 8 were 0.15 +/- 0.16 g/dL in the improved MHE group and -0.28 +/-
      0.33 g/dL in the non-improved MHE group, which differ significantly (P = 0.0130).
      CONCLUSION: Periodical nutritional management improved MHE and QOL. Improving the
      patient's nutritional condition may be one approach to treating MHE.

PMID- 22994430
TI  - Can long term therapy with oral nucleos(t)ide analogs influence the prognosis of
      chronic hepatitis B-related complications?

PMID- 22994431
TI  - Adrenal function in cirrhosis: the pendulum swings.

PMID- 22994432
TI  - The JGH foundation: facilitating education and research in the Asia-Pacific.

PMID- 22994433
TI  - Education and Imaging. Gastrointestinal: large heterotopic gastric mucosa in the
      rectum.

PMID- 22994434
TI  - Education and Imaging. Gastrointestinal: esophageal hematoma: a rare cause of
      upper gastrointestinal bleeding.

PMID- 22994435
TI  - Education and Imaging. Gastrointestinal: spontaneous jejunal hematoma secondary
      to supratherapeutic anticoagulation.

PMID- 22994436
TI  - Education and Imaging. Hepatobiliary and pancreatic: anomalous pancreaticobiliary
      junction and gallbladder cancer.

PMID- 22994437
TI  - Education and Imaging. Hepatobiliary and pancreatic: inferior mesenteric vein
      left gonadal vein shunt aggravating hepatic encephalopathy.

PMID- 22994438
TI  - Association between systemic neutrophil gelatinase-associated lipocalin and
      anemia, relative hypochromia, and inflammation in chronic systolic heart failure.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is upregulated systemically and
      by renal tubular cells in response to inflammation and ischemia. Recent interests
      in NGAL have focused on its ability to predict worsening renal function. However,
      as an iron-regulatory glycoprotein, the relationship between systemic NGAL levels
      and indices of anemia has not been examined. In 130 patients with chronic
      systolic heart failure, the authors examined the relationship between plasma NGAL
      levels and indices of anemia independent of underlying renal function and
      systemic markers of inflammation and oxidant stress. Plasma NGAL levels were
      significantly elevated in patients with anemia vs without anemia (121
      [interquartile range, 98-197] vs 72 [interquartile range, 57-98] ng/mL, P<.001).
      Plasma NGAL levels were inversely correlated with indices of anemia including red
      blood cell count (r=-0.38, P<.0001), hemoglobin (r=-0.41, P<.0001), and red cell
      distribution width (r=0.25, P=.007), even in patients with relatively preserved
      renal function (estimated glomerular filtration rate >=60 mL/min/1.73 m(2) ;
      n=83, P<.05 for all). Higher plasma NGAL levels were associated with presence of
      anemia independent of estimated glomerular filtration rate, plasma high
      sensitivity C-reactive protein, and myeloperoxidase levels (odds ratio, 2.38; 95%
      confidence interval, 1.02-6.20; P=.045). Hence, systemic NGAL levels are
      independently associated with indices of anemia.

PMID- 22994439
TI  - Risk score model for predicting mortality in advanced heart failure patients
      followed in a heart failure clinic.
AB  - The prevalence of heart failure (HF) in the population is increasing, concomitant
      with high incidence of rehospitalizations and mortality. The aim of this study
      was to characterize a prognostic risk score model for patients with chronic HF. A
      total of 500 patients followed at the HF clinic were evaluated by clinical,
      functional, laboratory, imaging, and therapeutic variables that were correlated
      to mortality during a follow-up period of 25 months. Risk stratification was
      carried out by applying a risk score model based on multivariate analysis.
      Predictors correlated with mortality during follow-up were systolic blood
      pressure <110 mm Hg, male sex, age older than 70 years, 6-minute walk distance
      <300 m, lack of beta-blocker therapy, hyperuricemia (>7.5 mg/dL), hyponatremia,
      and prolonged QTc interval (>450 ms). Based on these variables, a risk score
      model (score 0-55) was established and included low risk, score <21 (9% mortality
      during 2-year follow-up); moderate risk, 21 to 29 (22%); high risk, 30 to 35
      (35%), and very high risk: >=36 points (62% 2-year mortality). The risk model had
      good discrimination ability (concordance index 0.75), which was better than the
      performance of the Seattle Heart Failure Model on our cohort (0.69). Simple
      noninvasive characteristics examined during the initial admission to the HF
      clinic can serve as prognostic markers for mortality and may help in the process
      of therapeutic decision-making in patients with HF.

PMID- 22994440
TI  - A comparison of criterion standard methods to diagnose acute heart failure.
AB  - The authors sought to compare and contrast the clinical criterion standards
      currently used in a cohort of emergency department (ED) patients to diagnose
      acute heart failure syndromes (AHFS). In a prospective observational study of
      patients with signs and symptoms of AHFS, 3 criterion standards were examined:
      (1) the treating ED physician's diagnosis; (2) the hospital discharge diagnosis;
      and (3) a diagnosis based on medical record review by a panel of cardiologists.
      Using Cohen's kappa (kappa) coefficient, the authors assessed agreement and then
      compared the different standards by repeatedly setting one as the criterion
      standard and the other two as index tests. A total of 483 patients were enrolled.
      Across all criterion standards, patients with AHFS were more likely to have a
      history of AHFS, congestion on physical examination and chest radiography, and
      elevated natriuretic peptide levels than those without AHFS. The standards agreed
      well (cardiology review vs hospital discharge diagnosis, kappa=0.74; cardiology
      review vs ED diagnosis, kappa=0.66; ED diagnosis vs hospital discharge diagnosis
      kappa=0.59). Each method had similar sensitivity but differing specificities.
      Different criterion standards identify different patients from among those being
      evaluated for AHFS. Researchers should consider this when choosing between the
      various criterion standard approaches when evaluating new index tests.

PMID- 22994441
TI  - Ultrasound pleural effusion sign as a useful marker for identifying heart failure
      worsening in established heart failure patients during follow-up.
AB  - Clinical significance of UltraSound Pleural Effusion (US-PLE) and test
      characteristics of this sign for identifying worsening heart failure (HF) during
      follow-up of HF patients are unclear. Clinical records of 83 established HF
      patients were examined. The diagnosis of worsening HF was classified as "highly
      certain,""probable,""uncertain," or "no" based on the combination of the changes
      in symptoms/signs and B-type natriuretic peptide (BNP). Routine test included
      searching for the US-PLE sign. During a follow-up of 652+/-456 days, 1826 visits
      were evaluated. Among the 83 study patients, 78 had at least one of the
      following: worsening symptom(s), HF-related sign(s), and/or elevated BNP levels
      (>=3-fold increase) at one or more clinic visits. The US-PLE sign was present at
      83 visits of 49 study patients. Its appearance was associated with the presence
      of HF-related symptom(s)/sign(s) and BNP elevation (odds ratio, 53-177, P<.0001
      each). The test characteristics of the US-PLE sign for diagnosis of high
      possibility of worsening HF status fulfilling the "highly certain" or "probable"
      criteria were: sensitivity (76.6%), specificity (98.6%), positive predictive
      value (71.1%), and negative predictive value (99.0%). The US-PLE sign has high
      diagnostic accuracy for identifying worsening HF, including asymptomatic events,
      in HF patients during follow-up.

PMID- 22994442
TI  - Predictors of right ventricular systolic dysfunction in compensated and
      decompensated heart failure.
AB  - Current understanding of the mechanisms of right ventricular (RV) systolic
      dysfunction in heart failure (HF) is limited. The authors analyzed a limited
      access dataset from the Evaluation Study of Congestive Heart Failure and
      Pulmonary Artery Catheterization Effectiveness (ESCAPE) provided by the National
      Heart, Lung, and Blood Institute (NHLBI). RV systolic function was measured by
      echocardiography at baseline and at 3-month follow-up using fractional area
      change. Univariate and multivariate analysis was performed with linear
      regression. Of 433 patients enrolled in the ESCAPE trial, 190 had RV systolic
      function measured at baseline (decompensated HF) and 147 had it measured at 3
      month follow-up. On both occasions, parameters of congestion were associated with
      RV systolic function. Interestingly, lower hematocrit level was also associated
      with better RV systolic function. In multivariate analysis, only wedge pressure
      remained a statistically significant predictor of RV dysfunction. In summary,
      cardiac diastolic pressures and corresponding echocardiographic parameters, as
      well as hematocrit level, predicted RV systolic function in both compensated and
      decompensated systolic HF.

PMID- 22994443
TI  - Comparison of isoflavones and anthocyanins in soybean [Glycine max (L.) Merrill]
      seeds of different planting dates.
AB  - The concentrations of isoflavones and anthocyanins in five soybean seed cultivars
      of three different planting dates were determined in this study. Among the seeds
      of three different planting dates, the highest concentration of average total
      isoflavones (4098 MUg g(-1)) was measured in those from early July, whereas the
      lowest concentration of average total isoflavones (3238 MUg g(-1)) was measured
      in those from late May. Anthocyanin compounds were detected only in the
      Cheongjakong 3 cultivar. Among the three different planting dates, late-planted
      Cheongjakong 3 accumulated the highest concentration of total anthocyanins (10103
      MUg g(-1)), whereas the variety at an earlier planting date exhibited the lowest
      concentration of average total anthocyanins (7115 MUg g(-1)). On the basis of
      these results, it was concluded that environmental factors such as temperature
      and precipitation may change the isoflavone and anthocyanin contents of soybean,
      altering the nutritional values of soy products.

PMID- 22994444
TI  - Antihypertensive and cardioprotective effects of the Lagenaria siceraria fruit in
      NG-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats.
AB  - CONTEXT: Lagenaria siceraria (Molina) Standl. (Cucurbitacae) (LS) has been
      reported to possess cardioprotective, antihyperlipidemic, and diuretic
      activities. OBJECTIVE: To evaluate antihypertensive and cardioprotective effects
      of the Lagenaria siceraria fruit powder in N(G)-nitro-L-arginine methyl ester (L
      NAME) induced hypertension in rats. MATERIALS AND METHODS: Male Wistar rats were
      divided in four groups. Control 2% gum acacia p.o., L-NAME (40 mg/kg p.o.), LS
      (500 mg/kg p.o.) + L-NAME (40 mg/kg p.o.), L-arginine (100 mg/kg p.o.) + L-NAME
      (40 mg/kg p.o.). Treatment period was 4 weeks. On day 29 serum marker enzymes,
      cholesterol and heamodynamic parameters were measured. Histology of heart was
      performed. LS powder was characterized by HPLC. RESULT: Systolic blood pressures
      were increased by L-NAME (p < 0.001). In both drug treated groups systolic and
      diastolic blood pressures were reduced significantly (p < 0.001) compared to L
      NAME. In L-NAME group significantly (p < 0.01) elevated cholesterol which was
      reduced (p < 0.05) by LS treatment. In L-NAME group inflammation and necrosis (0
      35%) was present in heart whereas there was no change in myocardium of LS and L
      arginine treated rats. Vitexin, orientin and isoorientin were detected in
      methanol extract of LS powder. DISCUSSION AND CONCLUSION: L-NAME induced
      hypertension in rats was reduced by treatment with LS. The absence of necrosis,
      inflammation in the heart and significant reduction in serum cholesterol in LS
      and L-arginine treated rats indicated cardioprotective activity. Antioxidant
      activity of orientin and isoorientin appears to reduce the L-NAME induced damage.
      It is concluded that LS fruit possess antihypertensive and cardioprotective
      activity.

PMID- 22994445
TI  - Vaginal atrophy in breast cancer survivors: role of vaginal estrogen therapy.
AB  - Early menopause and related vaginal atrophy is a well known side-effect of
      hormone adjuvant treatment in breast cancer patients, particularly during
      aromatase-inhibitors therapy. Due to estrogens contra-indication, proper therapy
      for such symptom remains often an inadequately addressed clinical problem. After
      an accurate assessment of the risk/benefit ratio, vaginal low-dose estrogen
      treatment (better with estriol) [corrected] may have a role in controlling
      vaginal atrophy in selected and informed breast cancer women.

PMID- 22994446
TI  - Fibrinogen in massive haemorrhage--when and how should we replace it?

PMID- 22994447
TI  - The history of blood transfusion prior to the 20th century--part 1.
AB  - Blood transfusion, that is the transference of blood from the circulation of one
      individual to that of another for practical therapeutic purposes, is of
      relatively recent origin. Although it only became a routine practical possibility
      during and shortly after the Second World War, the concept of the infusion of
      blood has a much longer history. Practical transfusion has to some degree
      paralleled and in many instances been the consequence of developments in other
      sciences. However, the early history of blood transfusion is to some extent one
      of mysticism, professional rivalries, disregard of published work and a desire to
      maintain the status quo with regard to 'established medical procedure'. This
      article summarises some of the major aspects relating to the early history of
      blood transfusion.

PMID- 22994448
TI  - Cryoprecipitate: an outmoded treatment?
AB  - Cryoprecipitate is an allogeneic blood product prepared from human plasma. It
      contains factors VIII, von Willebrand factor (vWF), fibrinogen, fibronectin and
      factor XIII. Its use was first described in the 1960s for treatment of patients
      with factor VIII deficiency. It has also been used to treat patients with
      congenital hypofibrinogenaemia. Now, the most common use of cryoprecipitate is
      fibrinogen replacement in patients with acquired hypofibrinogenaemia and
      bleeding. Despite almost 50 years of use, evidence of efficacy is limited. This
      review provides an overview of the history of cryoprecipitate use, the current
      debates on the use of this product and future developments.

PMID- 22994449
TI  - The efficacy of fibrinogen concentrate compared with cryoprecipitate in major
      obstetric haemorrhage--an observational study.
AB  - BACKGROUND: Fibrinogen replacement is critical in major obstetric haemorrhage
      (MOH). Purified, pasteurised fibrinogen concentrate appears to have benefit over
      cryoprecipitate in ease of administration and safety but is unlicensed in
      pregnancy. In July 2009, the Irish Blood Transfusion Service replaced
      cryoprecipitate with fibrinogen. OBJECTIVES: To examine the impact of this
      externally imposed change on blood product use and clinical outcomes in MOH.
      METHODS: Women with MOH requiring fibrinogen between 1 January 2009 and 30 June
      2011 were identified from an MOH database. Aetiology of MOH, medical treatments,
      blood product use and clinical outcomes were compared between the cryoprecipitate
      and fibrinogen groups. RESULTS: Of 21 614 deliveries, 77 cases of MOH were
      identified. Of the 77 cases, 34 (44%) received cryoprecipitate (n = 14) or
      fibrinogen concentrate (n = 20). The mean (+/- SEM) dose utilised was 2.21 +/-
      0.35 pools of cryoprecipitate and 4 +/- 0.8 g of fibrinogen. There was a stronger
      correlation between the increase in fibrinogen level and dose of fibrinogen
      (Pearson co-efficient 0.5; P = 0.03) than dose of cryoprecipitate (Pearson co
      efficient 0.32; P = 0.3). Mean (+/- SEM) estimated blood loss (EBL), red cell
      concentrate (RCC) and Octaplas transfused were greater (but not significantly) in
      the cryoprecipitate group compared with the fibrinogen group; EBL = 5.2 +/- 1.1
      vs 3.3 +/- 0.5 L (P = 0.1); RCC = 7.2 +/- 1.2 vs 5.9 +/- 1.0 U (P = 0.4);
      Octaplas = 4.1 +/- 0.7 vs 3.2 +/- 0.7 U (P = 0.36), respectively. Haemostasis was
      secured, and there were no adverse reactions or thrombotic complications.
      CONCLUSION: Purified virally inactivated fibrinogen concentrate is as efficacious
      as cryoprecipitate in correcting hypofibrinogenaemia in MOH.

PMID- 22994450
TI  - Vasovagal reactions in Chinese blood donors: impact on donor return.

PMID- 22994451
TI  - Molecular epidemiological analysis of the transboundary transmission of 2003
      highly pathogenic avian influenza H7N7 outbreaks between the Netherlands and
      Belgium.
AB  - The 2003 outbreak of Highly pathogenic avian influenza (HPAI) A(H7N7) in the
      Netherlands, Belgium and Germany resulted in significant genetic diversification
      that proved informative for tracing transmission events. Building on previous
      investigations on the Dutch outbreak, we focused on the potential transnational
      transmissions between the Netherlands and Belgium. Although no clear
      epidemiological links could be identified from the tracing data, the transmission
      network based on concatenated HA-NA-PB2 sequences supports at least three
      independent introductions from the Netherlands to Belgium and suggests one
      possible introduction form Belgium back to the Netherlands. Two introductions in
      the Belgian province of Limburg occurred from nearby farms in the Dutch province
      of Limburg. One introduction resulted in three secondary infected farms, while a
      second introduction did not cause secondary infections. The third introduction
      into Belgium occurred in the north of the Antwerp province, very close to the
      national border, and originated from the North of the Dutch province Brabant
      (long distance transmission, >65 km). The virus spread to two additional Belgian
      farms, one of which may be the source of a secondarily infected farm in the
      Netherlands. One infected turkey farm in the province of Antwerp (Westmalle) was
      geographically close to the latter introduction, but genetically clustered with
      the first introduction event in the Limburg province. Epidemiological tracing
      data could neither confirm nor exclude whether this outbreak was a result from
      long distance contacts within Belgium or whether this farm presented a fourth
      independent transboundary introduction. These multiple transnational
      transmissions of HPAI in spite of reinforced biosecurity measures and trade
      restrictions illustrate the importance of international cooperation, legislation
      and standardization of tools to combat transboundary diseases. 

PMID- 22994452
TI  - Cardiovascular determinants of prognosis in normotensive hemodialysis patients.
AB  - BACKGROUND: Normotension has been hold to be the goal of hemodialysis. It remains
      obscure which cardiovascular parameter determines the prognosis in these
      normotensive hemodialysis patients. METHODS: We prospectively enrolled 145
      hemodialysis patients, who had attained normotension without anti-hypertensive
      medications, and followed them for 72.6 +/- 28.5 months. Important cardiovascular
      parameters were obtained at enrollment. Predictors for all-cause and
      cardiovascular mortalities were identified with the Cox model. RESULTS: There
      were 45 (18 cardiovascular/27 non-cardiovascular) deaths occurred during follow
      up. Age, diabetes, left ventricular mass index (LVMI), left ventricular ejection
      fraction (LVEF), carotid intima-media thickness (CIMT), and aortic pulse wave
      velocity (PWV) were significant predictors for all-cause and cardiovascular
      mortalities. After adjustment for age and diabetes, only LVEF was significantly
      associated with all-cause mortality. LVEF was significantly associated with
      cardiovascular mortality. LVEF remained as a significant independent predictor of
      cardiovascular death after adjusting for age, diabetes, LVMI, CIMT, or PWV,
      respectively. CONCLUSION: LVEF is the independent predictor for all-cause and
      cardiovascular mortalities in the normotensive hemodialysis patients.

PMID- 22994455
TI  - The development of a epsilon-polycaprolactone scaffold for central nervous system
      repair.
AB  - Potential treatment strategies for the repair of spinal cord injury (SCI)
      currently favor a combinatorial approach incorporating several factors, including
      exogenous cell transplantation and biocompatible scaffolds. The use of scaffolds
      for bridging the gap at the injury site is very appealing although there has been
      little investigation into the central nervous system neural cell interaction and
      survival on such scaffolds before implantation. Previously, we demonstrated that
      aligned microgrooves 12.5-25 MUm wide on epsilon-polycaprolactone (PCL) promoted
      aligned neurite orientation and supported myelination. In this study, we identify
      the appropriate substrate and its topographical features required for the design
      of a three-dimensional scaffold intended for transplantation in SCI. Using an
      established myelinating culture system of dissociated spinal cord cells,
      recapitulating many of the features of the intact spinal cord, we demonstrate
      that astrocytes plated on the topography secrete soluble factors(s) that delay
      oligodendrocyte differentiation, but do not prevent myelination. However, as
      myelination does occur after a further 10-12 days in culture, this does not
      prevent the use of PCL as a scaffold material as part of a combined strategy for
      the repair of SCI.

PMID- 22994453
TI  - Inherent sex-dependent regulation of human hepatic CYP3A5.
AB  - BACKGROUND AND PURPOSE: Expression of hepatic cytochromes P450 (CYP) in all
      species examined, including humans, is generally sexually dimorphic. We examined
      the sex-dependent expression of CYP3A5 and the hormone-regulated molecular
      mechanism(s) responsible for any dimorphism. EXPERIMENTAL APPROACH: CYP3A5 levels
      as well as nuclear translocation and promoter binding of transcription factors
      regulating CYP3A5 expression were measured in primary hepatocyte cultures derived
      from men and women exposed to physiological-like levels of growth hormone alone,
      dexamethasone alone and the combined regimen. KEY RESULTS: We observed a dramatic
      inherent CYP3A5 sexual dimorphism (women > men) with all treatments as a result
      of a ~2-fold greater level of hormone-induced activation and nuclear accumulation
      of hepatocyte nuclear factor-4alpha (HNF-4alpha), pregnane X receptor (PXR) and
      retinoic X receptoralpha (RXRalpha) in female hepatocytes. Furthermore, PXR :
      RXRalpha exhibited significantly higher DNA binding levels to its specific
      binding motif on the CYP3A5 promoter in female hepatocytes, inferring a possible
      explanation for the elevated expression of the isoform in women. Results from
      experiments using HepG2 cells treated with siRNA-induced knockdown of HNF-4alpha
      and/or transfected with luciferase reporter constructs containing the CYP3A5
      promoter were in agreement with the basic mechanism observed in primary
      hepatocytes of both sexes. CONCLUSIONS AND IMPLICATIONS: Female-predominant
      expression of human CYP3A5 is due to an inherent, sex-dependent suboptimal
      activation of the transcription networks responsible for hormone-induced
      expression of the isoform in men. Accordingly, in conjunction with previous
      studies of other human CYPs, men and women are intrinsically unlikely to handle
      many drugs in the same way; thus, sex should be a requisite component factored
      into the design of personalized drug therapies.

PMID- 22994457
TI  - Population-level effects of automated smoking cessation help programs: a
      randomized controlled trial.
AB  - AIMS: To test the population impact of offering automated smoking cessation
      interventions via the internet and/or by mobile phone. DESIGN: Pragmatic
      randomized controlled trial with five conditions: offer of (i) minimal
      intervention control; (ii) QuitCoach personalized tailored internet-delivered
      advice program; (iii) onQ, an interactive automated text-messaging program; (iv)
      an integration of both QuitCoach and onQ; and (v) a choice of either alone or the
      combined program. SETTING: Australia, via a mix of internet and telephone
      contacts. PARTICIPANTS: A total of 3530 smokers or recent quitters recruited from
      those interested in quitting, and seeking self-help resources (n = 1335) or cold
      contacted from internet panels (n = 2195). MEASUREMENTS: The primary outcome was
      self-report of 6 months sustained abstinence at 7 months post-recruitment.
      FINDINGS: Only 42.5% of those offered one of the interventions took it up to a
      minimal level. The intervention groups combined had a non-significantly higher 6
      month sustained abstinence rate than the control [odds ratio (OR) = 1.48; 95%
      confidence interval (CI): 0.98-2.24] (missing cases treated as smokers), with no
      differences between the interventions. Among those who used an intervention,
      there was a significant overall increase in abstinence (OR = 1.95; CI: 1.04
      3.67), but not clearly so when analysing only cases with reported outcomes.
      Success rates were greater among those recruited after seeking information
      compared to those cold-contacted. CONCLUSIONS: Smokers interested in quitting who
      were assigned randomly to an offer of either the QuitCoach internet-based support
      program and/or the interactive automated text-messaging program had non
      significantly greater odds of quitting for at least 6 months than those
      randomized to an offer of a simple information website.

PMID- 22994456
TI  - Only a small fraction of high-grade cervical lesions are discovered after an
      interpretation of atypical squamous cells of undetermined significance when using
      imager-assisted, liquid-based papanicolaou tests and the Bethesda 2001 system.
AB  - CONTEXT: Previous work has reported that most high-grade cervical neoplasia is
      seen in patients with preceding Papanicolaou test results of atypical squamous
      cells of undetermined significance. This information was based on conventional
      test results and the Bethesda 1991 reporting system and was determined before the
      current treatment guidelines. OBJECTIVE: Our objective was to perform a
      retrospective review of all histologically confirmed, high-grade cervical
      neoplasia to determine the diagnosis of the preceding liquid-based Papanicolaou
      test. DESIGN: A total of 189 histologically confirmed, high-grade cervical
      intraepithelial neoplasia (CIN) cases grade 2 and greater were identified for a 1
      year period. RESULTS: Of the 189 cases, 10 (5.3%) had a previous diagnosis of
      atypical squamous cells of undetermined significance; 55 (29.1%) had low-grade
      squamous intraepithelial lesions; 31 (16.4%) had low-grade squamous
      intraepithelial lesions, unable to rule out a high-grade squamous intraepithelial
      lesion; 21 (11.1%) had atypical squamous cells, unable to rule out a high-grade
      squamous intraepithelial lesion; 68 (36%) had high-grade squamous intraepithelial
      lesions; 1 (0.5%) had atypical glandular cells; 1 (0.5%) had adenocarcinoma in
      situ; and 2 (1%) had invasive carcinoma. Combined "low grade" Papanicolaou test
      results (atypical squamous cells of undetermined significance and low-grade
      squamous intraepithelial lesion) preceded 51 of 103 cases of CIN 2 (49.5%) and 14
      of 103 cases (13.6%) of CIN 3/cancer, whereas "high grade" Papanicolaou test
      results (atypical squamous cells, unable to rule out a high-grade squamous
      intraepithelial lesion; low-grade squamous intraepithelial lesions, unable to
      rule out a high-grade squamous intraepithelial lesion; high-grade squamous
      intraepithelial lesions; atypical glandular cells; adenocarcinoma in situ; and
      invasive carcinoma) preceded 52 of 103 CIN 2 cases (50.5%) and 72 of 103 CIN
      3/cancer cases (69.9%). CONCLUSIONS: Our data show that we can now more-reliably
      predict high-grade dysplasia on routine Papanicolaou tests. Only a small fraction
      of histologically confirmed CIN 2/3 cases are found following a Papanicolaou test
      diagnosis of atypical squamous cells of undetermined significance.

PMID- 22994458
TI  - A randomized controlled trial of a comprehensive migraine intervention prior to
      discharge from an emergency department.
AB  - OBJECTIVES: Patients who use an emergency department (ED) for acute migraine
      headaches have higher migraine disability scores, lower socioeconomic status, and
      are unlikely to have used a migraine-specific medication prior to presentation to
      the ED. The objective was to determine if a comprehensive migraine intervention,
      delivered just prior to ED discharge, could improve migraine impact scores 1
      month after the ED visit. METHODS:   This was a randomized controlled trial of a
      comprehensive migraine intervention versus typical care among patients who
      presented to an ED for management of acute migraine. At the time of discharge,
      for patients randomized to comprehensive care, the research team reinforced their
      diagnosis, shared a migraine education presentation from the National Library of
      Medicine, provided them with six tablets of sumatriptan 100 mg and 14 tablets of
      naproxen 500 mg, and if they wished, provided them with an expedited free
      appointment to the institution's headache clinic. Patients randomized to typical
      care received the care their attending emergency physicians (EPs) felt was
      appropriate. The primary outcome was a between-group comparison of the Headache
      Impact Test (HIT-6) score, a validated headache assessment instrument, 1 month
      after ED discharge. Secondary outcomes included an assessment of satisfaction
      with headache care and use of migraine-specific medication within that 1-month
      period. RESULTS:   Over a 19-month period, 50 migraine patients were enrolled.
      One-month follow-up was successfully obtained in 92% of patients. Baseline
      characteristics were comparable. One-month HIT-6 scores in the two groups were
      nearly identical (59 vs. 56, 95% confidence interval [CI] for difference of 3 = 
      5 to 11), as was dissatisfaction with overall headache care (17% vs. 18%, 95% CI
      for difference of 1% = -22% to 24%). Patients randomized to the comprehensive
      intervention were more likely to be using triptans or migraine-specific therapy
      (43% vs. 0%, 95% CI for difference of 43% = 20 to 63%) 1 month later.
      CONCLUSIONS: A comprehensive migraine intervention, when compared to typical
      care, did not improve HIT-6 scores (a validated measure of the effect of migraine
      on one's daily life) 1 month after ED discharge. Future work is needed to define
      a migraine intervention that is practical and useful in an ED, where many
      underserved patients, of necessity, present for care.

PMID- 22994459
TI  - Rapid and label-free single-nucleotide discrimination via an integrative
      nanoparticle-nanopore approach.
AB  - Single-nucleotide polymorphism (SNP) is an important biomarker for disease
      diagnosis, treatment monitoring, and development of personalized medicine. Recent
      works focused primarily on ultrasensitive detection, while the need for rapid and
      label-free single-nucleotide discrimination techniques, which are crucial
      criteria for translation into clinical applications, remains relatively
      unexplored. In this work, we developed a novel SNP detection assay that
      integrates two complementary nanotechnology systems, namely, a highly selective
      nanoparticle-DNA detection system and a single-particle sensitive nanopore
      readout platform, for rapid detection of single-site mutations. Discrete
      nanoparticle-DNA structures formed in the presence of perfectly matched (PM) or
      single-mismatched (SM) targets exhibited distinct size differences, which were
      resolved on a size-tunable nanopore platform to generate corresponding "yes/no"
      readout signals. Leveraging the in situ reaction monitoring capability of the
      nanopore platform, we demonstrated that real-time single-nucleotide
      discrimination of a model G487A mutation, responsible for glucose-6-phosphate
      dehydrogenase deficiency, can be achieved within 30 min with no false positives.
      Semiquantification of DNA samples down to picomolar concentration was carried out
      using a simple parameter of particle count without the need for sample labeling
      or signal amplification. The unique combination of nanoparticle-based detection
      and nanopore readout presented in this work brings forth a rapid, specific, yet
      simple biosensing strategy that can potentially be developed for point-of-care
      application.

PMID- 22994460
TI  - The rising incidence of eosinophilic oesophagitis is associated with increasing
      biopsy rates: a population-based study.
AB  - BACKGROUND: Eosinophilic oesophagitis (EoE) has evolved from a supposedly rare
      entity to one whose incidence rates are approaching that of inflammatory bowel
      disease. The factors responsible for this apparent increase in the incidence
      remain obscure. AIM: To assess various endoscopist and pathologist factors that
      might affect the frequency of EoE being detected in a well-defined North American
      population. HYPOTHESIS: Increased endoscopist and pathologist awareness has
      contributed to the increased clinical recognition of EoE. METHODS: Cases of EoE
      were identified systematically using population-based pathology and endoscopy
      databases from January 2004 to December 2008 in Calgary, Canada (population 1.25
      million). EoE frequency was estimated with time trend analysis. Characteristics
      of individual endoscopists (n = 45) were compared with diagnostic rates. RESULTS:
      Crude population incidence of EoE increased from 2.1 per 10(5) in 2004 to 11.0
      per 10(5) in 2008: an annual increase of 39% (P < 0.0001). The frequency in men
      was 4.5 times higher than in women (95% CI: 3.51-5.76). In patients presenting
      with dysphagia oesophageal biopsy rates increased from 17.0% in 2004 to 41.3% of
      EGDs in 2008: an annual rise of 26% (P < 0.0001). On multivariate regression
      analysis, those endoscopists with higher biopsy rates were more likely to make
      the diagnosis of EoE (P = 0.008). To include or exclude the diagnosis, typical
      histological features of EoE were reported more often by pathologists in 2008 as
      compared to 2004 (P = 0.01 & P < 0.0001 respectively). CONCLUSIONS: The incidence
      of eosinophilic oesophagitis continues to rise in the general population, in part
      due to increasing oesophageal biopsy rates and a more detailed histological
      evaluation of specimens. The biopsy rate of an endoscopist is an indicator for a
      higher diagnostic yield.

PMID- 22994461
TI  - The reason for clinical simulation.

PMID- 22994462
TI  - Clinical teaching associates in medical education: the benefits of certification.
AB  - BACKGROUND: Clinical teaching associates (CTAs) are human simulators who use
      themselves (i.e. their bodies and psyches) as an integral part of the teaching
      and assessing process. Increasingly, various CTAs are used in clinical education,
      for instance as stand-ins for clinical tutors or for high-stakes assessments.
      CONTEXT: Four groups of people have a stake in the competence of CTAs: patients
      (as they are at risk, both currently, in the clinical situation, and in the
      future if learners develop inappropriate behaviours that they later exhibit in
      their clinical work); learners (as their interaction with CTAs may be in a high
      stakes assessment); CTAs themselves (as they may wish to evidence their
      professional competence to new employers); and the organisations using them (as
      the reputation of the organisation depends on the competence of its faculty staff
      and graduates). INNOVATION: We argue that the professionalisation and
      certification of CTAs becomes more important as the total risk rises, using a
      three-dimensional matrix of risk (for patients), stakes (for learners) and
      responsibility (for CTAs). IMPLICATIONS: We suggest that the time is right for a
      colloquium to endeavour to agree standards for the certification of CTAs. This
      would be to the advantage of all stakeholders and would facilitate the use of
      CTAs in high-risk, high-stakes learning and assessment.

PMID- 22994463
TI  - How should we teach undergraduates in simulation scenarios?
AB  - BACKGROUND: Simulation is increasingly used by medical schools to prepare final
      year undergraduates for foundation year 1. But how should clinical teachers be
      delivering these simulation sessions to maximise the benefit to students? We
      sought to evaluate our own final-year simulation course, which uses two different
      styles of simulation, to identify the most effective method of practically
      delivering simulation-based teaching to final-year undergraduates. CONTEXT:
      Bristol Medical School recently introduced a new simulation course for final-year
      undergraduates. The course ran across two hospital sites. At hospital A, the
      students experienced real-time scenarios followed by brief feedback, whereas at
      hospital B, 'condensed' simulations were followed by longer feedback with
      teaching points. All students completed feedback questionnaires after each
      session, and seven students participated in a focus group. INNOVATION: Students
      felt that both styles of simulation equally achieved the objectives set by the
      Bristol Medical School, but also that each method had different strengths that
      added something very valuable to the learning experience. Students appreciated
      the detailed feedback they received in the condensed simulation sessions because
      it helped them to identify key improvements. The real-time simulation encouraged
      experiential learning and gave students an idea of the issues involved in real
      life emergency situations. Students also enjoyed the role-play element in the
      real-time simulation. IMPLICATIONS: The two different styles of simulation
      complement each other, and together provide a richer learning experience for
      students. We suggest that clinical teachers may wish to consider varying their
      styles of simulation teaching so as to maximise students' learning.

PMID- 22994464
TI  - Using simulation to support doctors in difficulty.
AB  - BACKGROUND: A small percentage of medical trainees will have performance concerns
      identified within their clinical practice. These trainees require specific
      interventions to address these concerns. The Postgraduate Ward Simulation
      Exercise (PgWSE) was developed as a joint collaboration between the University of
      Dundee and NHS Education for Scotland (NES). CONTEXT: The PgWSE takes around 90
      minutes to complete. It allows assessors to directly observe the performance of
      trainees within a simulated ward environment. Trainees are assessed individually
      on their ability to prioritise competing demands, work as part of a team and make
      safe informed clinical decisions. INNOVATION: The PgWSE is the first specific
      national intervention to support the assessment and remediation of trainee
      doctors in difficulty. Nine PgWSE scenarios have been developed to reflect
      clinical practice: three in general surgery, four in general medicine and two in
      medicine for the elderly. To enhance realism, simulated patients (SPs) are
      recruited and trained for each exercise. Standardised assessment tools were
      developed and validated for assessors to make individual and consensus judgements
      regarding a trainee's performance. Self-assessment of performance is used to
      disengage trainees from the simulated activity and to prepare them for
      constructive feedback. IMPLICATIONS: The PgWSE has been shown to be a valuable
      tool for the management of trainee doctors in difficulty in Scotland. Although
      the PgWSE is time and resource intensive, it has been shown to have a positive
      impact on the remediation of trainees and in the provision of objective, detailed
      and comprehensive feedback to the referring deanery. Within NES there are four
      geographical centres led by a postgraduate dean with responsibility for
      supervision of postgraduate medical education.

PMID- 22994465
TI  - An analysis of multisource feedback within the foundation programme.
AB  - INTRODUCTION: Multisource feedback (MSF) is a mandatory assessment in the
      foundation programme. The current tool that is used is the validated Team
      Assessment of Behaviour (TAB). This assesses doctors on four domains: maintaining
      trust and professional relations; verbal communication skills; teamworking; and
      accessibility. The aims of our retrospective analysis were to analyse the number
      of doctors who had an MSF with any type of concern, and to assess if there is any
      relationship between the number of MSFs submitted and the number of concerns and
      the staff group. METHOD: Data were obtained from the e-portfolio Malta database.
      The anonymized MSFs for the doctors in the foundation programme (FP) in Malta
      between July 2009 and July 2010 were analysed. RESULTS: A total of 1868 MSF
      assessments from 83 FP doctors (50 foundation year-1 doctors, FY1s, and 33 FY2s)
      were analysed. Fifty-two FY doctors were female. The majority of assessments
      (97.86%) did not show any concern in any of the four domains. However, at least
      one concern was raised for 21.7 percent of the doctors (12 FY1s and 6 FY2s). The
      chance of there being a concern reported was statistically significantly higher
      when the MSF was completed by a more senior doctor, rather than by an FY doctor
      or a nurse (p = 0.016). CONCLUSION: The aim of the MSF tool is to collate the
      views from a range of clinical colleagues in order to assess trainee performance.
      In our opinion, besides indicating when the MSFs should be performed and the
      minimum number that need to be submitted, it should also be mandatory that a
      certain proportion of MSFs should be performed by specific people (e.g. by a
      clinical supervisor, basic specialist trainee or higher specialist trainee
      working with the team).

PMID- 22994466
TI  - Multi-method needs assessment optimises learning.
AB  - BACKGROUND: Although needs assessment is an essential step in curricular
      development, postgraduate medical educators receive minimal associated training.
      Effective needs-assessment strategies include multi-method feedback from
      educators and learners. AIM: We describe the information received from three
      needs-assessment methods and analyse the advantages and disadvantages of each.
      METHODS: In the process of designing an evidence-based medicine (EBM) curriculum,
      we solicited learner and educator feedback using: (1) an anonymous needs
      assessment survey; (2) a curriculum committee consisting of volunteer learners
      and faculty members; and (3) a focus group containing a broader selection of
      learners. RESULTS: The survey generated quantitative data useful in lobbying for
      resources, but did not ascertain the meaning of surprising findings. The
      curriculum committee created learner buy-in for the curriculum and aided in
      curriculum design; however, it was time consuming. The focus group identified
      barriers to learning that influenced the curriculum but did not provide consensus
      on several critical issues. CONCLUSION: Each needs assessment tool delivered
      unique and valuable information. Educators performing needs assessment can select
      between these and other techniques based upon the information that they require.

PMID- 22994467
TI  - Diagnostic testing and educational assessment.
AB  - BACKGROUND: Clinicians are familiar with making diagnostic decisions based on
      information gathered from history, clinical examination and diagnostic tests.
      Although many clinicians assess students, they may be less familiar with ways to
      assimilate assessment information to inform educational decisions. We draw
      parallels between the processes used to make a clinical diagnosis and the similar
      processes needed to make an educational decision. CONTEXT: There are several
      indices that describe the performance and utility of diagnostic tests, which we
      have extrapolated to educational assessment. INNOVATION: We provide a clinical
      diagnostic question and an education assessment question, and use examples of
      indices of performance and utility for both of these situations to explore:
      reliability, indeterminate results, certainty in decisions, acceptable levels of
      sensitivity and specificity, pre-test probability and dealing with limitations.
      Test reliability requires adequate sampling and consistency between observers.
      Seeking more information should be targeted to situations where decisions are not
      certain. Altering score cut-points alters test sensitivity and specificity, which
      in assessment will alter the numbers of falsely passing or falsely failing
      candidates. Just as the pre-test probability of a diagnosis influences how to
      interpret diagnostic tests, so too does the pre-test probability of failure alter
      the performance characteristics of assessments. In clinical situations, a 'wait
      and see' approach may be limited by clinical urgency. Likewise, in assessment the
      'wait and see' approach may be limited by a duty to society. IMPLICATIONS:
      Clinicians familiar with the performance and utility of diagnostic tests can
      extrapolate that knowledge to make better interpretations of educational
      assessments.

PMID- 22994468
TI  - Teaching and learning in out-patient clinics.
AB  - BACKGROUND: Out-patient clinics offer trainees one of the most varied clinical
      experiences within the hospital setting, but they are often chaotic and over
      stretched, with limited time for teaching. An awareness of how to improve this
      learning environment by both trainers and trainees may enhance learning
      opportunities. CONTEXT: Clinical supervisors need to balance educational and
      service commitments, while maintaining a high quality of patient care.
      Supervision features observation and the sharing of clinical and continual
      feedback, which can improve clinical performance. Trainers must closely monitor
      the abilities of the trainee and gradually increase their responsibility and
      clinical load. INNOVATION: The application of learning theory to the workplace
      can improve learning opportunities. Trainers should have some control over the
      environment, both the physical attributes (room availability, staffing levels and
      allocated consultation time) and the harder to measure aspects, such as the ethos
      of the department and attitudes to teaching. The creation of a community of
      practice within out-patient clinics can strengthen both the collective knowledge
      of the team and its role in treating patients. The active involvement of trainees
      within this social environment (for example, by performing independent
      consultations) validates their role in the care of patients and enhances their
      learning. IMPLICATIONS: To maximise the learning opportunities within out-patient
      clinics there needs to be a shift in culture to promote learning in a safe and
      non-threatening environment. The establishment of a community of practice may
      validate the role of trainees in the management of patients and facilitate social
      learning by all members of the clinical team.

PMID- 22994469
TI  - Junior doctors' guide to portfolio learning and building.
AB  - BACKGROUND: A portfolio is a collection of evidence supporting an individual's
      achievement of competencies and learning outcomes. The material included in the
      portfolio must be reflected upon, as reflection provides the evidence that
      learning has taken place. CONTEXT: Portfolio learning is important for two
      principal reasons: assessment of the trainee, and for lifelong learning and
      reflection. The ability of a portfolio to be used for both summative and
      formative assessment makes it a flexible and robust assessment method. A
      portfolio also demonstrates reflection and lifelong learning abilities.
      Reflective learning is key to postgraduate medical education: it is part of both
      the Foundation Programme curriculum and General Medical Council guidance on best
      practice. INNOVATION: To ensure correct learning outcomes are identified and
      evidenced, the curriculum programme must be referred to and an educational
      supervisor should be consulted. Once identified, it is necessary to: identify how
      these outcomes can be met (learning needs); decide what needs to be done to meet
      these needs; reflect on what has been done; and evidence what has been done in
      the portfolio. Evidence could include written feedback, certificates of course
      completion, online learning modules, etc. IMPLICATIONS: A learning portfolio is a
      necessary tool for every postgraduate medical trainee. The portfolio serves to
      record and evidence all learning that has taken place, and thereon acts as a
      guide for future learning needs. The key process to portfolio building and
      learning is the provision of evidence by reflecting upon the learning that has
      taken place.

PMID- 22994470
TI  - Teaching skills for students: our future educators.
AB  - BACKGROUND: The future of medical education is under increasing strain from a
      paucity of clinical educators with formal teaching experience and time to fulfil
      their teaching roles. 'Teaching on the Run' (TOR), is a programme aimed at
      improving the quality of teaching by medical educators. We hypothesised that the
      completion of the TOR programme by senior medical students would increase student
      awareness of quality educational practice, thereby improving their competence and
      confidence in teaching and assessing their peers. METHODS: Seventeen senior
      medical students who participated in the TOR programme completed before and after
      questionnaires based on the key outcomes of the programme. All students were
      invited to participate in a focus group session to explore their attitudes and
      experiences of having completed the programme. Seven students chose to
      participate. RESULTS: The TOR increased students' perceived ability to apply
      educational principles, plan learning activities and to provide feedback. During
      the focus group session students expressed an appreciation that the medical
      school was genuinely interested in improving the quality of their teaching and
      learning. However, the programme did not improve students' confidence in
      assessing their peers. DISCUSSION: We found that the TOR programme may provide a
      foundation from which future medical educators may be trained. In particular,
      these students seem to have developed some understanding of the principles of
      adult learning, and may be better prepared to plan and deliver a teaching
      session. This augurs well for the future of medical education, which depends on
      the emergence of a new generation of trained medical educators.

PMID- 22994471
TI  - Stages of competency for medical procedures.
AB  - BACKGROUND: Basic medical procedures have historically been taught at the
      bedside, without a formal curriculum. The supervision of basic procedures is
      often provided by the next most senior member of the health care team, who
      themselves may have very little experience. This approach does not allow for
      preparatory reading or deliberate practise of the procedure, and trainees often
      track the number of completed procedures as the only evidence of competency,
      without documented assessments of quality. CONTEXT: The conscious competence
      model is a learning paradigm for acquiring a new skill that can be applied to
      teaching medical procedures. There are multiple stages for effectively learning
      how to competently perform a procedure, which should not be distilled down into
      bedside demonstration alone. Learners can be guided through these stages to allow
      progression towards competency to perform a procedure unsupervised. INNOVATION:
      We propose a novel approach that divides procedural education into a four-step
      process that covers knowledge, experience, technical skill development and
      competency evaluation. The stages of competency outlined here can be tailored,
      with incremental expectations for any medical procedure and any level of learner.
      IMPLICATIONS: This educational paradigm alters the current structure of teaching
      procedures at any level of medical education, with the goals of better
      comprehension, skill retention and decreased adverse outcomes. Graded objectives
      based on learner level can be determined by educators for each clinical
      procedure. This four-step framework for teaching medical procedures will make the
      adage 'see one, do one, teach one' obsolete.

PMID- 22994472
TI  - The distracted intravenous access (DIVA) test.
AB  - BACKGROUND: The General Medical Council states that all medical graduates must be
      able to carry out practical procedures, including peripheral venous cannulation,
      safely and effectively. Teaching and assessments within primary medical training
      tend to focus on safety rather than 'effectiveness' or technical competence. This
      study aimed to develop and evaluate a test of automaticity of peripheral venous
      cannulation skill, appropriate to the level of a medical student. METHODS: Two
      researchers developed the distracted intravenous access (DIVA) test. Three
      components are assessed simultaneously: ability to cannulate a plastic arm
      manikin, performance in an arithmetic test and speed of completion. Volunteers
      were recruited from three groups: novices (fourth-year medical students),
      intermediates (foundation year-1 doctors) and experts (anaesthetic and emergency
      medicine consultants and trainees). Immediately following the test, volunteers
      completed a questionnaire. RESULTS: Mean scores differed between the three
      groups: novices (47.7%), intermediates (73.4%), experts (84.4%). Differences were
      statistically significant (p < 0.0005). The majority of participants found the
      test to be enjoyable (78%) and useful (76%). More students agreed that the test
      was fair (78%) than doctors (38%), but this difference was not statistically
      significant. DISCUSSION: This study presents a feasible method of testing medical
      students' automaticity when performing peripheral venous cannulation. It has
      provided evidence of the construct validity and acceptability of the test. The
      authors suggest that clinical tutors consider offering the test as a formative
      assessment to final-year medical students in order to familiarise them with the
      level of proficiency required to perform peripheral venous cannulation when
      distracted.

PMID- 22994473
TI  - Communication training for international graduates.
AB  - INTRODUCTION: International Medical Graduates (IMGs) are more likely to be
      involved in complaints and have lower pass rates for professional examinations.
      Language barriers and differences in culture and consulting style are suggested
      to be the cause. A programme was developed in Dumfries and Galloway to address
      these issues, aiming to provide language and consultation skills training, and
      create a culture where these issues could be discussed openly. METHODS: There was
      voluntary recruitment of participants to a programme of consultation and language
      skills delivered by experienced general practitioner (GP) trainers and an
      experienced language tutor. The course was assessed using objective measurement
      of language and consultation skills and feedback from participants, tutors and
      educational supervisors. RESULTS: The programme was fully subscribed with a wide
      range of experience amongst participants, although the absolute numbers were
      small. Objective improvement was seen in all areas of language assessed, with
      improvements also seen in consultation skills. The programme was popular with
      educational supervisors and with participants, who would all like to see it
      continue. The tutors noted that participants became increasingly reflective, and
      also believe that the course should continue. CONCLUSIONS: The programme was
      valued by all those involved, and showed that short-term interventions can
      improve language and consultation skills, potentially helping to address the
      challenges faced by this particular group of doctors.

PMID- 22994474
TI  - Anxiety about anxiety in medical undergraduates.
AB  - BACKGROUND: Effective communication with patients is a vital ability for a
      doctor, and therefore training in communication skills forms an important
      component of the undergraduate medical curriculum. However, some medical
      undergraduates experience anxiety in communicating with patients and this makes
      it difficult for them to communicate with patients effectively. We developed
      workshops to equip students with skills to reduce communication-related anxiety,
      but turnout was low and only female students participated. PURPOSES: This study
      investigated the barriers that existed to workshop participation in order to
      inform the development of future workshops. METHODS: Semi-structured interviews
      with medical students who were completing their pre-clinical training (n = 16)
      were carried out. Interviews were transcribed and thematically analysed. RESULTS:
      Participants recognised symptoms of anxiety, and some reported experiencing it
      when speaking with patients. Participants acknowledged that the workshops would
      be useful to some students. Labelling the workshops as dealing with 'anxiety'
      contributed to non-participation, as students perceived their attendance as
      potentially showing weakness to fellow students and to medical school staff. Our
      findings indicated that the stigma attached to seeking guidance for communication
      related anxiety is exacerbated for male students and by the competitive medical
      school environment. CONCLUSIONS: Attitudes towards 'anxiety' and experiencing
      anxiety can act as a barrier towards seeking support for communication-related
      anxiety.

PMID- 22994475
TI  - Is the post-take ward round standardised?
AB  - BACKGROUND: The importance of the post-take ward round to both patient safety and
      medical education cannot be overemphasised. Despite this, significant variation
      exists between consultants and senior doctors in the conduct and content of ward
      rounds. This discrepancy prompted the idea of using a checklist to audit whether
      essential components were being consistently addressed during post-take ward
      rounds. This would allow an exploration of whether introducing a checklist would
      benefit both patient safety and medical education. METHODS: The post-take ward
      round was audited by a small group of medical students over a few months using a
      checklist. This checklist contained 17 evidence-based items that had been
      identified as important for patient safety. A number of different consultants
      were included in the audit. RESULTS: Results of the audit analysis confirmed that
      there was significant variability between consultants in both the approach and
      the content of the post-take ward round. Although some areas were completed most
      of the time, there were other areas in which inconsistent approaches were
      demonstrated. DISCUSSION: As such variability was demonstrated between
      consultants in their conduct of the ward rounds, it was concluded that the
      introduction of this checklist would provide a standardised approach that junior
      doctors could learn from. Therefore, the introduction of this checklist into
      clinical practice was identified as a worthwhile teaching resource for juniors in
      order to enhance patient safety and foundation doctor learning.

PMID- 22994476
TI  - Medicine, law, ethics: teaching versus learning.
AB  - PURPOSE: Doctors' anxieties about the legal environment begin during medical
      school. The signals faculty members send to medical students contribute to this
      anxiety. A pilot study was conducted to examine signals sent by faculty members
      to students regarding the relationship of legal risk management and ethical
      patient care at one medical school. It was also intended to determine the
      agreement between the messages faculty staff believe they are transmitting and
      those that students think they are hearing from faculty mentors. METHODS: A
      survey with six multiple-choice questions was sent electronically to clinical
      faculty staff of one medical school to elicit the signals faculty members send
      students regarding the relationship of legal risk management and ethical patient
      care. A complementary survey instrument was sent to all 240 third- and fourth
      year students to elicit their perceptions of what they were being taught by their
      mentors about the legal environment. Responses were tabulated, analysed, and
      interpreted. RESULTS: Faculty staff and student responses to six questions
      regarding teaching and learning about the relationship of legal risk management
      and ethical patient care revealed, for four of the six questions, statistically
      significantly different perspectives between what faculty members thought they
      were teaching and what students thought they were learning. CONCLUSIONS: Medical
      schools should be teaching patient-centered medicine, reconciling an awareness of
      the legal environment with the provision of ethically and clinically sound
      patient care. To improve performance, we must address the messages faculty
      members send students and reduce the disparity between perceived faculty teaching
      and claimed student learning in this context.

PMID- 22994478
TI  - Leadership.

PMID- 22994480
TI  - Workplace-based assessments: friend or foe.

PMID- 22994481
TI  - Segregated seating in the lecture hall.

PMID- 22994482
TI  - The rainbow nation has a spectrum of opportunities.

PMID- 22994483
TI  - Anatomic reference for computed tomography of paranasal sinuses and their
      communication in the Egyptian buffalo (Bubalus bubalis).
AB  - The purpose of this work was to present an anatomic reference for computed
      tomography (CT) for the paranasal sinuses of adult buffalo fit the use of
      anatomists, radiologists, clinicians and veterinary students. CT images with the
      most closely corresponding cross sections of the head were selected and studied
      serially in a rostral to caudal progression from the level of the interdental
      space to the level of the nuchal line. The anatomical features were compared with
      the dissected heads and skulls. The paranasal sinuses of buffalo comprise dorsal
      conchal, middle conchal, maxillary, frontal, palatine, sphenoidal (inconstant,
      small and shallow when present), lacrimal and ethmoidal that were identified and
      labelled according to the premolar and molar teeth as landmarks. The topographic
      description of all the compartments, diverticula, septa and communication of the
      paranasal sinuses in buffalo has been presented. The relationship between the
      various air cavities and paranasal sinuses was easily visualized.

PMID- 22994485
TI  - Effect of fluorine substitution on the aromaticity of polycyclic hydrocarbons.
AB  - The effect of fluorine substitution on the aromaticity of polycyclic hydrocarbons
      (PAH) is investigated. Magnetically induced current densities, current pathways,
      and current strengths, which can be used to assess molecular aromaticity, are
      calculated using the gauge-including magnetically induced current method (GIMIC).
      The degree of aromaticity of the individual rings is compared to those obtained
      using calculated nucleus-independent chemical shifts at the ring centers (NICS(0)
      and NICS(0)(zz)). Calculations of explicitly integrated current strengths for
      selected bonds show that the aromatic character of the investigated polycyclic
      hydrocarbons is weakened upon fluorination. In contrast, the NICS(0) values for
      the fluorinated benzenes increase noteworthy upon fluorination, predicting a
      strong strengthening of the aromatic character of the arene rings. The integrated
      current strengths also yield explicit current pathways for the studied molecules.
      The current pathways of the investigated linear polyacenes, pyrene, anthanthrene,
      coronene, ovalene, and phenanthro-ovalene are not significantly affected by 
      fluorination.  NISC(0) and NICS(0)(zz) calculations provide contradictory degrees
      of aromaticity of the fused individual ring. Obtained NICS values do not
      correlate with the current strengths circling around the individual rings.

PMID- 22994484
TI  - MALDI imaging of post-mortem human spinal cord in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease
      of the central nervous system that is characterized by motor neuron degeneration
      in the brainstem and the spinal cord. Matrix-assisted laser desorption/ionization
      (MALDI) imaging mass spectrometry is an emerging powerful technique that allows
      for spatially resolved, comprehensive, and specific characterization of molecular
      species in situ. In this study, we report for the first time the MALDI imaging
      based spatial protein profiling and relative quantification of post-mortem human
      spinal cord samples obtained from ALS patients and controls. In normal spinal
      cord, protein distribution patterns were well in line with histological features.
      For example, thymosin beta 4, ubiquitin, histone proteins, acyl-CoA-binding
      protein, and macrophage inhibitory factor were predominantly localized to the
      gray matter. Furthermore, unsupervised statistics revealed a significant
      reduction of two protein species in ALS gray matter. One of these proteins (m/z
      8451) corresponds to an endogenous truncated form of ubiquitin (Ubc 1-76), with
      both C-terminal glycine residues removed (Ubc-T/Ubc 1-74). This region-specific
      ubiquitin processing suggests a disease-related change in protease activity.
      These results highlight the importance of MALDI mass spectrometry as a versatile
      approach to elucidate molecular mechanisms of neurodegenerative diseases.

PMID- 22994486
TI  - A fortunate journey on uneven grounds.
AB  - I was surprised to be invited to write a prefatory chapter for the Annual Review
      of Microbiology. Indeed, I did not feel that I belonged to that class of eminent
      scientists who had written such chapters. Perhaps it is because I am a kind of
      mutant: In spite of having experienced war, both German and Soviet occupations,
      repeated bombardments, dictatorships, and a revolution, I managed nonetheless to
      engage in scientific research, thus realizing a childhood dream. After having
      obtained my Doctor Rerum Naturalium degree in Budapest, Hungary, I was fortunate
      to meet Jacques Monod at the Pasteur Institute, and this became a turning point
      in my scientific career. In his laboratory, I contributed to the definition of
      the lactose operon promoter, uncovered intracistronic complementation in beta
      galactosidase, and investigated the role of cAMP in Escherichia coli. In my own
      laboratory, together with many gifted students and collaborators, I studied the
      role of adenylate cyclase in bacterial virulence. This allowed the engineering of
      recombinant adenylate cyclase toxin from Bordetella pertussis for the development
      of protective and therapeutic vaccines.

PMID- 22994487
TI  - Memories of a senior scientist: on passing the fiftieth anniversary of the
      beginning of deciphering the genetic code.
AB  - 2011 marked the fiftieth anniversary of breaking the genetic code in 1961.
      Marshall Nirenberg, the National Institutes of Health (NIH) scientist who was
      awarded the Nobel Prize in Physiology or Medicine in 1968 for his role in
      deciphering the code, wrote in 2004 a personal account of his research. The race
      for the code was a competition between the NIH group and Severo Ochoa's
      laboratory at New York University (NYU) School of Medicine, where I was a
      graduate student and conducted many of the experiments. I am now 83 years old.
      These facts prompt me to recall how I, together with Joe Speyer, an instructor in
      the Department of Biochemistry at NYU, unexpectedly became involved in
      deciphering the code, which also became the basis of my PhD thesis. Ochoa won the
      Nobel Prize in Physiology or Medicine in 1959 for discovering polynucleotide
      phosphorylase (PNP), the first enzyme found to synthesize RNA in the test tube.
      The story of how PNP made the deciphering of the code feasible is recalled here.

PMID- 22994488
TI  - 'Gestalt,' composition and function of the Trypanosoma brucei editosome.
AB  - RNA editing describes a chemically diverse set of biomolecular reactions in which
      the nucleotide sequence of RNA molecules is altered. Editing reactions have been
      identified in many organisms and frequently contribute to the maturation of
      organellar transcripts. A special editing reaction has evolved within the
      mitochondria of the kinetoplastid protozoa. The process is characterized by the
      insertion and deletion of uridine nucleotides into otherwise nontranslatable
      messenger RNAs. Kinetoplastid RNA editing involves an exclusive class of small,
      noncoding RNAs known as guide RNAs. Furthermore, a unique molecular machinery,
      the editosome, catalyzes the process. Editosomes are megadalton multienzyme
      assemblies that provide a catalytic surface for the individual steps of the
      reaction cycle. Here I review the current mechanistic understanding and molecular
      inventory of kinetoplastid RNA editing and the editosome machinery. Special
      emphasis is placed on the molecular morphology of the editing complex in order to
      correlate structural features with functional characteristics.

PMID- 22994489
TI  - Physiology and diversity of ammonia-oxidizing archaea.
AB  - The discovery of ammonia-oxidizing archaea (AOA), now generally recognized to
      exert primary control over ammonia oxidation in terrestrial, marine, and
      geothermal habitats, necessitates a reassessment of the nitrogen cycle. In
      particular, the unusually high affinity of marine and terrestrial AOA for ammonia
      indicates that this group may determine the oxidation state of nitrogen available
      to associated micro- and macrobiota, altering our current understanding of
      trophic interactions. Initial comparative genomics and physiological studies have
      revealed a novel, and as yet unresolved, primarily copper-based pathway for
      ammonia oxidation and respiration distinct from that of known ammonia-oxidizing
      bacteria and possibly relevant to the production of atmospherically active
      nitrogen oxides. Comparative studies also provide compelling evidence that the
      lineage of Archaea with which the AOA affiliate is sufficiently divergent to
      justify the creation of a novel phylum, the Thaumarchaeota.

PMID- 22994490
TI  - Bacterial persistence and toxin-antitoxin loci.
AB  - Bacterial persistence is caused by the presence of rare, slowly growing bacteria
      among populations of rapidly growing cells. The slowly growing bacteria are
      tolerant of antibiotics and other environmental insults, whereas their isogenic,
      rapidly growing siblings are sensitive. Recent research has shown that
      persistence of the model organism Escherichia coli depends on toxin-antitoxin
      (TA) loci. Deletion of type II TA loci reduces the level of persistence
      significantly. Lon protease but no other known ATP-dependent proteases is
      required for persistence. Polyphosphate and (p)ppGpp also are required for
      persistence. These observations led to the proposal of a simple and testable
      model that explains the persistence of E. coli. It is now important to challenge
      this model and to test whether the persistence of pathogenic bacteria also
      depends on TA loci.

PMID- 22994492
TI  - DNA replication and genomic architecture of very large bacteria.
AB  - Large cell size is not restricted to a particular bacterial lifestyle, dispersal
      method, or cell envelope type. What is conserved among the very large bacteria
      are the quantity and arrangement of their genomic resources. All large bacteria
      described to date appear to be highly polyploid. This review focuses on
      Epulopiscium sp. type B, which maintains tens of thousands of genome copies
      throughout its life cycle. Only a tiny proportion of mother cell DNA is inherited
      by intracellular offspring, but surprisingly DNA replication takes place in the
      terminally differentiated mother cell as offspring grow. Massive polyploidy
      supports the acquisition of unstable genetic elements normally not seen in
      essential genes. Further studies of how large bacteria manage their genomic
      resources will provide insight into how simple cellular modifications can support
      unusual lifestyles and exceptional cell forms.

PMID- 22994493
TI  - Large T antigens of polyomaviruses: amazing molecular machines.
AB  - The large tumor antigen (T antigen) encoded by simian virus 40 is an amazing
      molecular machine because it orchestrates viral infection by modulating multiple
      fundamental viral and cellular processes. T antigen is required for viral DNA
      replication, transcription, and virion assembly. In addition, T antigen targets
      multiple cellular pathways, including those that regulate cell proliferation,
      cell death, and the inflammatory response. Ectopic T antigen expression results
      in the immortalization and transformation of many cell types in culture and T
      antigen induces neoplasia when expressed in rodents. The analysis of the
      mechanisms by which T antigen carries out its many functions has proved to be a
      powerful way of gaining insights into cell biology. The accelerating pace at
      which new polyomaviruses are being discovered provides a collection of novel T
      antigens that, like simian virus 40, can be used to discover and study key
      cellular regulatory systems.

PMID- 22994491
TI  - A virological view of innate immune recognition.
AB  - The innate immune system uses multiple strategies to detect viral infections.
      Because all viruses rely on host cells for their synthesis and propagation, the
      molecular features used to detect viral infections must be unique to viruses and
      absent from host cells. Research in the past decade has advanced our
      understanding of various cell-intrinsic and cell-extrinsic modes of virus
      recognition. This review examines the innate recognition from the point of view
      of virus invasion and replication strategies, and places innate sensors in the
      context of detecting viral genome, replication intermediate, transcriptional by
      product, and other viral invasion strategies. On the basis of other unique
      features common to viral infections, undiscovered areas of virus detection are
      discussed.

PMID- 22994494
TI  - Peroxisome assembly and functional diversity in eukaryotic microorganisms.
AB  - Peroxisomes are core eukaryotic organelles that generally function in lipid
      metabolism and detoxification of reactive oxygen species, but they are
      increasingly associated with taxa-specific metabolic, cellular, and developmental
      functions. Here, we present a brief overview of peroxisome assembly, followed by
      a discussion of their functional diversification. Matrix protein import occurs
      through a remarkable translocon that can accommodate folded and even oligomeric
      proteins. Metabolically specialized peroxisomes include glycosomes of
      trypanosomes, which have come to compartmentalize most of the glycolytic pathway
      and play a role in developmental signal transduction. The differentiation of
      physically distinct subcompartments also contributes to peroxisome
      diversification; in the clade of filamentous ascomycetes, dense-core Woronin
      bodies bud from peroxisomes to gate cell-to-cell channels. Here, the import of
      oligomeric cargo is central to the mechanism of subcompartment specification. In
      general, the acquisition of a tripeptide peroxisome targeting signal by
      nonperoxisomal proteins appears to be a recurrent step in the evolution of
      peroxisome diversity.

PMID- 22994495
TI  - Bacterial chemotaxis: the early years of molecular studies.
AB  - This review focuses on the early years of molecular studies of bacterial
      chemotaxis and motility, beginning in the 1960s with Julius Adler's pioneering
      work. It describes key observations that established the field and made bacterial
      chemotaxis a paradigm for the molecular understanding of biological signaling.
      Consideration of those early years includes aspects of science seldom described
      in journals: the accidental findings, personal interactions, and scientific
      culture that often drive scientific progress.

PMID- 22994497
TI  - Network news: the replication of kinetoplast DNA.
AB  - One of the most fascinating and unusual features of trypanosomatids, parasites
      that cause disease in many tropical countries, is their mitochondrial DNA. This
      genome, known as kinetoplast DNA (kDNA), is organized as a single, massive DNA
      network formed of interlocked DNA rings. In this review, we discuss recent
      studies on kDNA structure and replication, emphasizing recent developments on
      replication enzymes, how the timing of kDNA synthesis is controlled during the
      cell cycle, and the machinery for segregating daughter networks after
      replication.

PMID- 22994498
TI  - Editorial comment to stage-specific impact of extended versus standard pelvic
      lymph node dissection in radical cystectomy.

PMID- 22994496
TI  - The unique paradigm of spirochete motility and chemotaxis.
AB  - Spirochete motility is enigmatic: It differs from the motility of most other
      bacteria in that the entire bacterium is involved in translocation in the absence
      of external appendages. Using the Lyme disease spirochete Borrelia burgdorferi
      (Bb) as a model system, we explore the current research on spirochete motility
      and chemotaxis. Bb has periplasmic flagella (PFs) subterminally attached to each
      end of the protoplasmic cell cylinder, and surrounding the cell is an outer
      membrane. These internal helix-shaped PFs allow the spirochete to swim by
      generating backward-moving waves by rotation. Exciting advances using
      cryoelectron tomography are presented with respect to in situ analysis of cell,
      PF, and motor structure. In addition, advances in the dynamics of motility,
      chemotaxis, gene regulation, and the role of motility and chemotaxis in the life
      cycle of Bb are summarized. The results indicate that the motility paradigms of
      flagellated bacteria do not apply to these unique bacteria.

PMID- 22994499
TI  - Sweating liquid micro-marbles: dropwise condensation on hydrophobic
      nanoparticulate materials.
AB  - Liquid marbles have opened up several potential applications including
      biochemical batch reaction engineering and gas sensing. To be successful
      candidates in these applications, the ability to prepare liquid marbles of
      controlled sizes and in a continuous process is crucial. This has been the
      missing link in the science leading to these applications. In the current study,
      we present a remarkably simple process driven by condensation on a
      nanoparticulate matrix to continuously produce liquid marbles whose mean size can
      be controlled in the range of diameters from 3 to 1000 MUm, while the
      distribution width is also controllable independently. We experimentally
      demonstrate the physics involved in this condensation-driven marble formation
      process using two fluids-glycerol and ethylene glycol-which span an order of
      magnitude in viscosity. Hydrophobic fumed silica nanoparticulate material is used
      as the encapsulating medium owing to its intertwined agglomerate nature. We show
      that the primary mechanism causing the formation of liquid marbles is droplet
      nucleation followed by growth driven by condensation. Drop coalescence in dense
      droplet ensembles is the secondary mechanism, which attempts to destroy the
      distribution width controllability. From a physics perspective, it will be
      demonstrated that strong coalescence dominated growth gives rise to a hitherto
      unreported, significantly higher rate of growth.

PMID- 22994500
TI  - Diuretics aggravate zinc deficiency in patients with liver cirrhosis by
      increasing zinc excretion in urine.
AB  - AIM: Liver cirrhosis is often accompanied by zinc deficiency. The exact
      mechanisms underlying zinc deficiency remain unclear. This study was undertaken
      to clarify the influence of diuretics on blood zinc levels and zinc excretion in
      urine in liver cirrhosis. METHODS: Seventy-nine outpatients with liver cirrhosis
      were divided into four groups: (i) patients receiving no zinc preparations or
      diuretics (LC group); (ii) those receiving zinc preparations only (LCZ group);
      (iii) those receiving diuretics only (LCD group); and (iv) those receiving both
      zinc preparations and diuretics (LCDZ group). Among these groups, the effects of
      the administrated drugs on blood zinc levels and urinary zinc excretion were
      analyzed. RESULTS: Blood zinc levels were significantly lower in the LCD group
      (47.8 +/- 10.5 MUg/dL) than in the other groups (LC: 68.8 +/- 17.1 MUg/dL, P =
      0.0056, post-hoc test; LCZ: 78.4 +/- 18.1, P < 0.0001; LCDZ: 70.3 +/- 21.4, P =
      0.0008). The creatinine-adjusted urinary zinc excretion was significantly higher
      in the LCDZ group (548.1 +/- 407.6 MUg/mg creatinine) than in the other groups
      (LC, 58.5 +/- 43.7; LCZ, 208.1 +/- 227.8; LCD, 105.2 +/- 154.4; each P < 0.0001).
      The fraction of urinary zinc excretion was also significantly higher in the LCDZ
      group (5.6 +/- 2.9%) than in the other groups (LC, 0.6 +/- 0.5; LCD, 1.7 +/- 1.5;
      LCZ, 1.6 +/- 1.2; each P < 0.0001). CONCLUSION: In patients with liver cirrhosis,
      treatment with diuretics can increase zinc excretion by suppressing the
      reabsorption of zinc through renal tubules, which might lead to zinc deficiency.

PMID- 22994501
TI  - Functionalization density dependent toxicity of oxidized multiwalled carbon
      nanotubes in a murine macrophage cell line.
AB  - The present study investigates the effect of functionalization density on the
      toxicity and cellular uptake of oxidized multiwalled carbon nanotubes (f-MWCNTs)
      in vitro. The toxicity of f-MWCNTs at varying degrees of carboxylation was
      assessed in a murine macrophage RAW 264.7 cell line, a model for liver Kupffer
      cells. In vitro cytotoxicity of oxidized MWCNTs was directly proportional to
      their functionalization density. The increased cytotoxicity was associated with a
      concurrent increase in the number of apoptotic cells and production of reactive
      nitrogen species (RNS). In contrast, reactive oxygen species (ROS) generation was
      the highest in the case of pristine MWCNTs and decreased with increased
      functionalization density. Quantitative cellular uptake studies indicated that
      endogenous ROS production was independent of the concentration of CNTs
      internalized by a specific cell population and was directly proportional to their
      surface hydrophobicity. Mechanistic studies suggested that cellular uptake of
      CNTs was critically charge-dependent and mediated through scavenger receptors,
      albeit the involvement of nonscavenger receptor mechanisms at low CNT
      concentrations and their saturation at the experimental concentration cannot be
      ruled out. A mathematical model was established to correlate between the cellular
      uptake of CNTs with their length and zeta potential. In an attempt to correlate
      the results of in vitro toxicity experiments with those of the in vivo toxicity
      in the mouse model, we found that the toxicity trends in vitro and in vivo are
      rather opposing. The apparent anomaly was explained on the basis of different
      experimental conditions and doses associated with cells under in vivo and in
      vitro culture conditions.

PMID- 22994502
TI  - Everolimus  in the treatment of hormone receptor-positive breast cancer.
AB  - INTRODUCTION: The phosphoinositide triphosphate kinase (PI3K)/AKT/mammalian
      target of rapamycin (mTOR) is a central regulatory pathway involved in cell
      proliferation, growth, differentiation, metabolism and survival. Deregulation of
      this pathway is well described in breast cancer and is associated to the
      development of endocrine resistance among hormone receptor (HR)-positive tumors.
      Everolimus , an mTOR-inhibitor has clinical activity against breast cancer and
      has shown to restore sensitivity to endocrine therapy. AREAS COVERED: We review
      the clinical data and the results of the recently published clinical trials
      evaluating the use of everolimus in HR-positive breast cancer patients in
      combination with endocrine therapy. We discuss the data regarding efficacy but
      also describe in detail the side effect profile of this drug. EXPERT OPINION:
      Everolimus represents a new therapeutic alternative for the treatment of HR
      positive metastatic breast cancer. Everolimus is in general a well-tolerated
      drug, however, stomatitis, fatigue and hematological abnormalities are common. It
      is still unclear if there are specific subgroups of patients that receive greater
      benefit from everolimus and whether there is a relationship between the presence
      of PIK3CA mutations and efficacy. The results of biomarker studies will hopefully
      provide information that will help us determine which patients are most likely to
      benefit from this treatment.

PMID- 22994503
TI  - The evidence in evidence-based practice. Why the confusion?

PMID- 22994504
TI  - Theme issue on the Dental Trauma Guide.

PMID- 22994505
TI  - Dental Trauma Guide: a source of evidence-based treatment guidelines for dental
      trauma.
AB  - Diagnosis and treatment for traumatic dental injuries are very complex owing to
      the multiple trauma entities represented by six luxation types and nine fracture
      types affecting both the primary and the permanent dentition. When it is further
      considered that fracture and luxation injuries are often combined, the result is
      that more than 100 trauma scenarios exist, when the two dentitions are combined.
      Each of these trauma scenarios has a specific treatment demand and prospect for
      healing. With such a complexity in diagnosis and treatment, it is obvious that
      even experienced practitioners may have problems in selecting proper treatment
      for some of these trauma types. To remedy this situation, an Internet-based
      knowledge base consisting of 4000 dental trauma cases with long-term follow up is
      now available to the public and the professions on the Internet using the address
      http://www.DentalTraumaGuide.org. It is the aspiration that the use of this Guide
      may lead the practitioner to offer an evidence-based diagnosis and treatment.

PMID- 22994507
TI  - Role of the ribose-specific marker furfuryl-amine in the formation of aroma
      active 1-(furan-2-ylmethyl)-1H-pyrrole (or furfuryl-pyrrole) derivatives.
AB  - Furfuryl-pyrroles possess a diverse range of organoleptic properties described as
      roasted, chocolaty, green, horseradish-like, and mushroom-like and are detected
      in various foods such as coffee, chocolate, popcorn, and roasted chicken.
      Although their origin in food was attributed to furfuryl-amine, the latter has
      not been detected so far in Maillard model systems or in foods. In this study,
      furfuryl-amine was shown to be formed specifically from ribose through nitrogen
      atom transfer from the alpha-amino group of any amino acid. Such a transfer can
      be achieved through decarboxylation of the Schiff base adduct and isomerization
      followed by hydrolysis. Through the use of (15)Nalpha-lysine it was revealed that
      only the (15)Nalpha nitrogen atom was incorporated into its structure, indicating
      a specific role for the carboxylate moiety in the mechanism of its formation.
      Furthermore, isotope labeling studies have indicated that furfuryl-pyrrole
      derivatives can be formed by the interaction of 2 mol of furfuryl-amine with 3
      deoxyribosone followed by dehydration and cyclization to form 1-(furan-2-yl)-N
      {[1-(furan-2-ylmethyl)-1H-pyrrol-2-yl]methylidene}methanamine. After hydrolysis,
      this intermediate can generate furfuryl-formyl-pyrrole, furfuryl-pyrrole
      carboxylic acid, and furfuryl-pyrrole. In this study, the furfuryl-amine
      derivatives were also detected in different coffee beans after pyrolysis and
      analysis by GC-MS. The potential of these compounds to form in aqueous model
      systems at a temperature of 120  degrees C was also demonstrated. 

PMID- 22994508
TI  - The Ruby UCSC API: accessing the UCSC genome database using Ruby.
AB  - BACKGROUND: The University of California, Santa Cruz (UCSC) genome database is
      among the most used sources of genomic annotation in human and other organisms.
      The database offers an excellent web-based graphical user interface (the UCSC
      genome browser) and several means for programmatic queries. A simple application
      programming interface (API) in a scripting language aimed at the biologist was
      however not yet available. Here, we present the Ruby UCSC API, a library to
      access the UCSC genome database using Ruby. RESULTS: The API is designed as a
      BioRuby plug-in and built on the ActiveRecord 3 framework for the object
      relational mapping, making writing SQL statements unnecessary. The current
      version of the API supports databases of all organisms in the UCSC genome
      database including human, mammals, vertebrates, deuterostomes, insects,
      nematodes, and yeast.The API uses the bin index-if available-when querying for
      genomic intervals. The API also supports genomic sequence queries using locally
      downloaded *.2bit files that are not stored in the official MySQL database. The
      API is implemented in pure Ruby and is therefore available in different
      environments and with different Ruby interpreters (including JRuby). CONCLUSIONS:
      Assisted by the straightforward object-oriented design of Ruby and ActiveRecord,
      the Ruby UCSC API will facilitate biologists to query the UCSC genome database
      programmatically. The API is available through the RubyGem system. Source code
      and documentation are available at https://github.com/misshie/bioruby-ucsc-api/
      under the Ruby license. Feedback and help is provided via the website at
      http://rubyucscapi.userecho.com/.

PMID- 22994509
TI  - Special topic on the many faces of hypoxia.

PMID- 22994510
TI  - IX World Congress on High Altitude Medicine and Physiology, Taipei, Taiwan,
      November 3-6, 2012.

PMID- 22994513
TI  - Clinician's corner: What do we know about safe ascent rates at high altitude?
AB  - Although pharmacologic strategies are available for decreasing the risk of acute
      altitude illness, the best means of preventing these problems remains undertaking
      an adequately slow ascent. Guidelines regarding appropriate ascent rates have
      been published in various forums, and while these guidelines are generally
      similar to each other in regards to the recommended ascent rates and use of rest
      days, there is actually little evidence in the literature supporting the
      particular recommendations. The purpose of this review is to consider these
      guidelines and the issue of ascent rates in greater detail. Following a
      discussion of the evidence regarding ascent rates and acclimatization, the review
      considers several unanswered questions regarding the current guidelines,
      including the applicability of the guidelines for all altitude travelers, how
      best to determine the ascent rate, how to implement rest days, and whether pre
      acclimatization strategies can be used to facilitate faster than recommended
      ascents. Given the current state of evidence, there is no reason to alter the
      current guidelines, as they likely work for the substantial majority of high
      altitude travelers. It is individuals traveling to high altitude for the first
      time for whom they remain most important, while those individuals with
      substantial prior experience at high altitude may opt for faster or slower ascent
      rates based on their prior experience. Rest days should remain a part of any
      ascent profile and should be used following any large gains in elevation rather
      than simply at specified time intervals. Pre-acclimatization strategies may
      decrease the risk of acute altitude illness but there is insufficient evidence to
      suggest they can be used to facilitate faster than recommended ascents. Further
      research may allow changes in practice in the future but for the time being,
      adherence to the current recommendations is the prudent approach for the majority
      of high altitude travelers.

PMID- 22994514
TI  - HIF-1 at the blood-brain barrier: a mediator of permeability?
AB  - The importance of the blood-brain barrier (BBB) in maintaining brain homeostasis
      cannot be better appreciated than during disease states, where disruption of its
      function is associated with dramatic detrimental clinical outcome. For decades,
      neuroscientists and neurobiologists investigated most neurological diseases under
      the prism of a neuro-centric view, considering the contribution of non-neural
      components of the CNS (BBB, choroid plexus) negligible or even irrelevant.
      However, recent reviews have highlighted the importance of BBB breakdown in major
      neurological diseases. Hypoxia, as well as hypoxia/reoxygenation, are key
      components of many neurological diseases and have been shown to contribute to
      barrier disturbance and dysfunction significantly. Since the master regulator of
      the hypoxic response, hypoxia inducible factor 1 (HIF-1), is a key determinant
      for adaptation of cells and tissues to oxygen deprivation, it is likely that this
      transcription factor also plays a key role in barrier permeability. The possible
      future use of HIF-1 stabilizers for treatment of diseases characterized by oxygen
      deprivation to increase neuronal/cell survival means this question is now very
      pertinent. This review will focus its attention on the role of HIF-1 in BBB
      breakdown following hypoxic/ischemic injury and the implications for such
      therapies in a clinical setting.

PMID- 22994515
TI  - Hypoxia-mediated regulation of stem cell fate.
AB  - Hypoxia-mediated regulation of stem cell fate, or reduced oxygen availability, is
      a prominent feature during mammalian development and under physiological and
      pathological conditions in adults. Oxygen-sensing is therefore indispensable as
      it enables the cells to adapt instantaneously to an inappropriate pO(2). This
      machinery relies primarily on hypoxia inducible factor (HIF). Moreover, a growing
      body of evidence proposes that different types of stem cells exist in a very
      hypoxic microenvironment, which may be beneficial for the maintenance of these
      cells and ensures continuous replenishment of dead or damaged cells in virtually
      all tissues of the body. Recent reports have shown that HIF is a critical player
      in these responses. However, a better understanding of the different HIF-related
      mechanisms is of utmost importance for the improvement of therapeutic strategies
      for tissue regeneration as well as hematological malignancies.

PMID- 22994516
TI  - Hypoxia in the eye: a two-sided coin.
AB  - Tissue oxygenation in general and hypoxia in particular are important regulators
      of retinal physiology and pathophysiology. Reduced oxygen tension and hypoxia
      inducible transcription factors along with some of their target genes are
      critically involved in retinal development, and especially in the generation of a
      normal retinal vasculature. Well-timed hypoxia is thus vital for the young eye to
      establish proper retinal function and vision. However, when hypoxia is ill-timed,
      reduced oxygen tension may be associated with the development of retinal
      pathologies, including retinopathy of prematurity, diabetic retinopathy,
      glaucoma, age-related macular degeneration, or high altitude retinopathy. Here,
      reduced oxygen tension activates a hypoxic response that culminates in an
      increased expression of vascular endothelial growth factor. This causes
      pathological neovascularization of the delicate neuronal retina, a process that
      may ultimately lead to loss of vision. In contrast, preconditioning by well
      defined and controlled short-term hypoxia is not devastating for the retina but
      instead induces a molecular response that provides protection to neuronal cells.
      Detailed investigation of hypoxic mechanisms during development and adulthood may
      thus reveal factors, which may be targeted by therapeutic approaches to save and
      preserve vision in patients.

PMID- 22994517
TI  - The hypoxic placenta.
AB  - Hypoxia of the placenta is integral to complications of pregnancy, including
      preeclampsia, intrauterine growth restriction, and small-for-gestational age
      babies. Hypoxia in the placenta is associated with vascular remodeling,
      hypertension, metabolic changes, oxidative stress, mitochondrial dysfunction, and
      endoplasmic reticular stress. Hypoxia induces similar outcomes in other organs
      such as the lungs, kidney, and gut. Comparing and contrasting the effects of
      hypoxia on placental functions and functions of lung, kidney, and gut can lead to
      novel hypotheses and investigations, furthering our understanding of the impact
      of hypoxia on these diverse yet similar organs. In this review, we compare and
      contrast hypoxic placental responses to those in the other organ and cell
      systems.

PMID- 22994518
TI  - Visual analogue self-assessment of acute mountain sickness in adolescents:
      experience from two Himalayan expeditions.
AB  - OBJECTIVE: Recent studies have investigated visual analogue scales (VAS) as an
      alternative to the Lake Louise AMS Self-Report Score (LLS) for the self
      assessment of acute mountain sickness (AMS). We investigated their use in
      adolescents. METHODS: The study was conducted during the 2009 and 2010 British
      Schools Exploring Society 35-day expeditions to Ladakh. Comparable ascent
      profiles were followed, reaching a maximum altitude of 6000 m. LLS and VAS AMS
      scores were recorded each morning. VAS comprised 100 mm lines for each LLS
      symptom; VAS scores were summed to give a composite daily total (VAS(c),
      expressed as a percentage). In 2010, an additional line was used to score overall
      "altitude sickness' (VAS(o)). RESULTS: 42 individuals participated in 2009 (83%
      compliance; mean age 17.4 years); 28 in 2010 (82% compliance; 17.5 years). 759
      data points were recorded in 2009; 529 in 2010. There was a significant
      correlation between LLS and VAS(c) on both expeditions (rho=0.80, p<0.001 in
      2009; rho=0.65, p<0.001 in 2010). These significant correlations remained when
      cases of AMS were analyzed separately. However, in all cases, the relationship
      between LLS and VAS was distorted, with a tendency for VAS to underscore symptoms
      of AMS when LLS<5. A VAS(c) value of 5.5% had an 82% specificity and sensitivity
      for all cases of AMS; VAS(c) of 9.5% had a 90% specificity and sensitivity for
      moderate and severe AMS. CONCLUSIONS: Whilst adolescents are capable of self
      monitoring for AMS using VAS, the relationship with LLS is distorted. The LLS,
      despite its limitations, therefore remains the preferred method for the self
      assessment of AMS in adolescents.

PMID- 22994519
TI  - Optic nerve sheath diameter is not related to high altitude headache: a
      randomized controlled trial.
AB  - The mechanism of high altitude headache (HAH) remains unknown. The aim of this
      study was to determine experimentally whether optic nerve sheath diameter (ONSD),
      as an indicator of intracranial pressure, is related to HAH. Following sea level
      measurements at 3 and 12 hours (SL), 23 subjects were passively transported to
      high altitude (3777 m, HA) via cable car. HAH, ONSD, arterial oxygen saturation
      (Spo(2)), and fluid balance were determined at 3, 12, 24, and 36 hours. After 12
      hours exposure to HA, subjects were classified by visual analogue scale (VAS) as
      either HAH positive (HAH+) or HAH negative (HAH-). Acetazolamide (250 mg) or
      placebo was then randomly prescribed at 15, 20, and 28 hours. Outcome means were
      compared via analysis of variance, and relationships between variables were
      analyzed by longitudinal regression. Acetazolamide had no statistically
      significant effect on HAH (p=0.63) or ONSD (p=0.98), but produced a negative
      fluid balance (p<0.01) (and also increased Spo(2) in exploratory analyses).
      Spo(2) was lower in HAH+ than HAH- [85 (3)% versus 88 (2)%, p=0.03).
      Nevertheless, ONSD increased similarly in HAH+ and HAH- (interaction p=0.90).
      ONSD also remained significantly elevated above SL values for the entire HA
      period [SL, 5.2 (0.5) versus HA, 5.6 (0.5) mm, p<0.01], despite headache
      resolving with acclimatization [VAS: SL, 1/100 (3) mm versus HA 3 h, 9/100 (13);
      12 h, 10/100 (14); 24 h, 8/100 (12); 36 h, 1/100 (4) mm, p<0.01]. Furthermore,
      HAH was significantly correlated with Spo(2) (beta=-1.39, p<0.01) but not with
      ONSD (beta=0.59, p=0.57). These data do not support that intracranial pressure is
      associated with the development or amelioration of mild HAH. Clinical trial
      registration NCT01288781.

PMID- 22994520
TI  - Termination of cardiopulmonary resuscitation in mountain rescue.
AB  - The aim was to establish scientifically supported recommendations for termination
      of cardiopulmonary resuscitation (CPR) in mountain rescue, which can be applied
      by physicians and nonphysicians. A literature search was performed; the results
      and recommendations were discussed among the authors, and finally approved by the
      International Commission for Mountain Emergency Medicine (ICAR MEDCOM) in October
      2011. 4166 abstracts were reviewed; of these, 96 were relevant for this article
      and are included in this literature review. In mountain rescue, CPR may be
      withheld or terminated in a patient with absent vital signs when the risk is
      unacceptable to the rescuer, the rescuer is exhausted or in extreme environments
      where CPR is not possible or any of the following apply: decapitation; truncal
      transection; whole body incinerated, decomposed, or frozen solid; avalanche
      victim in asystole with obstructed airway and burial time >35 min. Also, CPR may
      be terminated when all of the following criteria apply: unwitnessed loss of vital
      signs, no return of spontaneous circulation during 20 min of CPR, no shock
      advised at any time by AED or only asystole on ECG, and no hypothermia or other
      special circumstances warranting extended CPR. In situations where transport is
      not possible, mitigation of special circumstances is not possible, and further
      resuscitation is futile, CPR should be terminated. Medical directors of rescue
      teams should interpret these recommendations in the context of local conditions
      and laws, and create team-specific training and protocols for determining when to
      withhold and terminate CPR in a patient with absent vital signs.

PMID- 22994522
TI  - Bosentan reduces pulmonary artery pressure in high altitude residents.
AB  - Endothelin-1 (ET-1) plays a critical role in the regulation of pulmonary vascular
      tone. The aim of this study was to investigate the role of ET-1 in the
      pathogenesis of high altitude pulmonary arterial hypertension (HAPH). METHODS:
      Pulmonary artery pressure (PAP) was measured by echocardiography in permanent
      residents of the Kyrgyz Republic (3200-4000 m above sea level) both before and 3
      h after a single oral dose of ET receptor antagonist, bosentan (125 mg). Plasma
      ET-1 levels were measured by ELISA assay. Genomic DNA was extracted from
      peripheral blood samples and the frequency of -3a and -4a alleles of the ET-1
      gene determined by PCR. RESULTS: Plasma ET-1 in HAPH highlanders was
      significantly higher than in healthy subjects (7.05+/-2.35 vs. 4.65+/-1.65 pg/ml,
      p<0.002). After the treatment with 125 mg bosentan, systolic PAP decreased from
      46+/-1.9 to 37+/-2.2 mm Hg (p<0.01), and pulmonary artery acceleration time
      (PAAT) increased from 0.086+/-0.001 to 0.098+/-0.001 sec (p<0.001). The frequency
      of the -4a allele was significantly higher in HAPH patients compared to healthy
      highlanders (0.43 vs. 0.3, chi(2)=4.3, p=0.03). CONCLUSION: Increased ET-1 levels
      play an important role in development of HAPH.

PMID- 22994521
TI  - Effect of endothelin receptor antagonist bosentan on chronic hypoxia-induced
      inflammation and chemoafferent neuron adaptation in rat carotid body.
AB  - Chronic hypoxia (CH) induces an inflammatory response in rat carotid body that is
      characterized by immune cell invasion and the expression of pro-inflammatory
      cytokines. In the present study, we have investigated the role of type-A
      endothelin (ET-A) receptors in the development of CH-induced inflammation. After
      7 days of CH (380 Torr), double-label immunofluorescence studies demonstrated
      elevated levels of ET-A receptor and tyrosine hydroxylase (TH) in O(2)-sensitive
      type I cells. Following CH, ET-A receptors were also expressed on resident and
      invasive CD45+ immune cells distributed in tissue surrounding chemosensory cell
      lobules. Immnofluorescence and quantitative PCR studies showed that concurrent
      treatment with the ET-A/B receptor antagonist, bosentan (200 mg/kg/day), blocked
      CH-induced ED-1+ macrophage invasion and the upregulation of cytokines, including
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha
      (TNFalpha), and monocyte chemoattractant protein-1 (MCP-1). Moreover, bosentan
      treatment blocked the CH-induced increases in expression of acid-sensitive ion
      channels (ASICs) in chemoafferent neurons in the petrosal ganglion (PG). Our
      findings are consistent with the hypothesis that CH-induced inflammation involves
      the upregulation and release of ET-1 from type I cells. ET-1 may act in an
      autocrine/paracrine mechanism via ET-A receptors on chemosensory type I cells and
      immune cells to promote an inflammatory response.

PMID- 22994523
TI  - Arnold Durig (1872-1961): life and work. An Austrian pioneer in exercise and high
      altitude physiology.
AB  - Arnold Durig (1872-1961) grew up in the Austrian mountains in the period when
      intense exploration of the Alps started. As an enthusiastic mountaineer,
      scientist, and physician, he became one of the pioneers exploring physiological
      and pathophysiological aspects of humans sojourning to high altitudes. At the
      beginning of the 20(th) century, Durig was one of the great physiologists whose
      knowledge covered the whole field of physiology. Durig founded a renowned School
      and his students spread all over the world. He stayed in close contact with many
      colleagues and famous scientists, such as Albert Einstein and Sigmund Freud.
      Although he was an extremely productive and acknowledged physiologist and teacher
      at that time, his work and life are not very well known at the beginning of the
      3(rd) millennium, even by high altitude physiologists. Thus, this article
      provides an overview on Durig's life and work, highlighting the most important
      scientific studies he performed at moderate and high altitudes, in an attempt to
      provide a few links to the development of high altitude research in the late
      19(th) and early 20(th) centuries, complemented by some comments from a current
      point of view.

PMID- 22994524
TI  - Cell salvage for obstetric patients who decline blood transfusion: a national
      survey.

PMID- 22994525
TI  - Mineral and bone disorder in Chinese dialysis patients: a multicenter study.
AB  - BACKGROUND: Mineral and bone disorder (MBD) in patients with chronic kidney
      disease is associated with increased morbidity and mortality. Studies regarding
      the status of MBD treatment in developing countries, especially in Chinese
      dialysis patients are extremely limited. METHODS: A cross-sectional study of 1711
      haemodialysis (HD) patients and 363 peritoneal dialysis (PD) patients were
      enrolled. Parameters related to MBD, including serum phosphorus (P), calcium
      (Ca), intact parathyroid hormone (iPTH) were analyzed. The achievement of MBD
      targets was compared with the results from the Dialysis Outcomes and Practice
      Study (DOPPS) 3 and DOPPS 4. Factors associated with hyperphosphatemia were
      examined. RESULTS: Total 2074 dialysis patients from 28 hospitals were involved
      in this study. Only 38.5%, 39.6% and 26.6% of them met the Kidney Disease
      Outcomes Quality Initiative (K/DOQI) defined targets for serum P, Ca and iPTH
      levels. Serum P and Ca levels were statistically higher (P < 0.05) in the HD
      patients compared with those of PD patients, which was (6.3 +/- 2.1) mg/dL vs
      (5.7 +/- 2.0) mg/dL and (9.3 +/- 1.1) mg/dL vs (9.2 +/- 1.1) mg/dL, respectively.
      Serum iPTH level were statistically higher in the PD patients compared with those
      of HD patients (P = 0.03). The percentage of patients reached the K/DOQI targets
      for P (37.6% vs 49.8% vs 54.5%, P < 0.01), Ca (38.6% vs 50.4% vs 56.0%, P < 0.01)
      and iPTH (26.5% vs 31.4% vs 32.1%, P < 0.01) were lower among HD patients,
      compared with the data from DOPPS 3 and DOPPS 4. The percentage of patients with
      serum phosphorus level above 5.5 mg/dL was 57.4% in HD patients and 47.4% in PD
      patients. Age, dialysis patterns and region of residency were independently
      associated with hyperphosphatemia. CONCLUSIONS: Status of MBD is sub-optimal
      among Chinese patients receiving dialysis. The issue of hyperphosphatemia is
      prominent and needs further attention.

PMID- 22994526
TI  - Applying response surface methodology to optimize nimesulide permeation from
      topical formulation.
AB  - Nimesulide is a non-steroidal anti-inflammatory drug that acts through selective
      inhibition of COX-2 enzyme. Poor bioavailability of this drug may leads to local
      toxicity at the site of aggregation and hinders reaching desired therapeutic
      effects. This study aimed at formulating and optimizing topically applied lotions
      of nimesulide using an experimental design approach, namely response surface
      methodology. The formulated lotions were evaluated for pH, viscosity,
      spreadability, homogeneity and in vitro permeation studies through rabbit skin
      using Franz diffusion cells. Data were fitted to linear, quadratic and cubic
      models and best fit model was selected to investigate the influence of permeation
      enhancers, namely propylene glycol and polyethylene glycol on percutaneous
      absorption of nimesulide from lotion formulations. The best fit quadratic model
      explained that the enhancer combination at equal levels significantly increased
      the flux and permeability coefficient. The model was validated by comparing the
      permeation profile of optimized formulations' predicted and experimental response
      values, thus, endorsing the prognostic ability of response surface methodology. 

PMID- 22994529
TI  - Longitudinal analysis of integrase N155H variants in heavily treated patients
      failing raltegravir-based regimens.
AB  - OBJECTIVES: The mechanism of raltegravir (RAL)-resistant evolutions has not
      already been elucidated. Because the emergence of RAL resistance is usually
      initiated by the N155H mutant, we assessed the role of minor N155H-mutated
      variants in circulating RNA and archived DNA in five heavily treated patients
      experiencing long-term RAL therapy failure and harbouring three different
      resistance profiles determined by standard genotyping. METHODS: Allele-specific
      polymerase chain reaction (AS-PCR) was used to detect N155H mutants in
      longitudinal stored plasma and whole-blood samples before, during and after RAL
      based regimens in five patients infected with the HIV-1 B subtype. RESULTS: No
      minor N155H-mutated variant was found by AS-PCR in either plasma or whole-blood
      samples collected at baseline and after RAL withdrawal in any of the five
      patients. During RAL failure, the mutation N155H was detected at different levels
      in three patients displaying the N155H pathway and gradually declined when the
      double mutant Q148H+G140S was selected in one patient. In two patients with the
      Q148H resistance pathway, no N155H variant was identified by AS-PCR in either
      viral RNA or DNA. CONCLUSIONS: The N155H mutation present at various levels from
      minority to majority showed no relationship with the three RAL-associated
      resistance profiles, suggesting that this mutant may not play a role in
      determining different resistance profiles. Moreover, pre-existing N155H is very
      infrequent and, if selected during RAL failure, the N155H mutant disappears
      quickly after RAL withdrawal.

PMID- 22994530
TI  - Moral philosophers are moral experts! A reply to David Archard.
AB  - In his article 'Why Moral Philosophers Are Not and Should Not Be Moral Experts'
      David Archard attempts to show that his argument from common-sense morality is
      more convincing than other competing arguments in the debate. I examine his main
      line of argumentation and eventually refute his main argument in my reply. 

PMID- 22994528
TI  - New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2.
AB  - The present-day concept of drug efficacy has changed completely from its original
      description as the property of agonists that causes tissue activation. The
      ability to visualize the multiple behaviours of seven transmembrane receptors has
      shown that drugs can have many efficacies and also that the transduction of drug
      stimulus to various cellular stimulus-response cascades can be biased towards
      some but not all pathways. This latter effect leads to agonist 'functional
      selectivity', which can be favourable for the improvement of agonist
      therapeutics. However, in addition, biased agonist potency becomes cell type
      dependent with the loss of the monotonic behaviour of stimulus-response
      mechanisms, leading to potential problems in agonist quantification. This has an
      extremely important effect on the discovery process for new agonists since it now
      cannot be assumed that a given screening or lead optimization assay will
      correctly predict therapeutic behaviour. This review discusses these ideas and
      how new approaches to quantifying agonist effect may be used to circumvent the
      cell type dependence of agonism. This article, written by a corresponding member
      of the International Union of Basic and Clinical Pharmacology Committee on
      Receptor Nomenclature and Drug Classification (NC-IUPHAR), reviews our current
      understanding of the interaction of ligands with seven transmembrane receptors.
      Further information on these pharmacological concepts is being incorporated into
      the IUPHAR/BPS database GuideToPharmacology.org.

PMID- 22994531
TI  - Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury.
AB  - INTRODUCTION: The cavernous nerve (CN) is commonly injured during prostatectomy,
      resulting in erectile dysfunction (ED). Although peripheral nerves have a limited
      ability to regenerate, a return of function typically does not occur due to
      irreversible down stream morphological changes in the penis that result from CN
      injury. We have shown in previous studies that sonic hedgehog (SHH) is critical
      for CN regeneration and improves erectile function after crush injury. AIMS:
      Examine a new direction, to determine if SHH is neuroprotective to the pelvic
      ganglia (PG)/CN after crush injury. A secondary focus is to examine if SHH
      signaling decreases with age in the PG/CN. METHODS: Sprague-Dawley rats underwent
      bilateral CN crush and SHH and glial fibrillary acidic protein were quantified by
      western analysis of the PG/CN (N = 6 rats at each time point) at 1, 2, 4, 7, and
      14 days, and the apoptotic index was measured in the penis. SHH was quantified by
      western in the PG/CN with blockade of anterograde transport (N = 4 rats) in
      comparison to mouse IgG (N = 4 rats). If SHH is neuroprotective was examined at 4
      (N = 14 rats) and 7 days (N = 16 rats) of treatment after CN crush. SHH protein
      was quantified in aging (P200-300, N = 5 rats) PG/CN in comparison to normal
      adult (P115-120, N = 3 rats) PG/CN. Main Outcome Measures.  SHH pathway was
      examined in PG via immunohistochemistry, in situ, western, and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). RESULTS: SHH is
      neuroprotective in the PG/CN with injury. SHH localization in the PG/CN suggests
      SHH interaction in neuronal/glial signaling. SHH protein is significantly
      decreased in the PG/CN after crush injury and in the aged PG/CN. Signals from the
      PG are required to maintain SHH in the CN. CONCLUSIONS: There is a window of
      opportunity immediately after nerve insult in which manipulation of SHH signaling
      in the nerve microenvironment can affect long-term regeneration outcome.

PMID- 22994532
TI  - Geographical variation in reproductive ageing patterns and life-history strategy
      of a short-lived passerine bird.
AB  - We investigated differences in ageing patterns in three measures of breeding
      performance in populations of barn swallows Hirundo rustica L. from Spain and
      Denmark differing in breeding latitude and hence migration distance and duration
      of the breeding season. We found differences in ageing patterns between
      populations. Generally, young (i.e. yearling) and old females (i.e. >= 5 years of
      age) laid their first eggs later and produced smaller clutches than middle-aged
      females (i.e. 2-4 years of age) in both populations. The southernmost population
      (i.e. Spanish) showing the shorter migratory distance experienced a greater
      within-individual increase in timing of breeding and clutch size in early life
      and a greater within-individual decrease in laying date but not in clutch size
      during senescence compared with the northernmost population (i.e. Danish). We
      also found that the number of fledglings produced annually was related to the age
      of the two members of the breeding pairs with pairs composed of young and old
      females performing less well than breeding pairs composed of middle-aged females.
      We did not find reproductive senescence for the age of the male while controlling
      for the age of the female on the number of fledglings produced annually by the
      breeding pair. Differential survival between individuals did not explain age
      effects on laying date or annual clutch size in neither population. However, the
      increase in the number of fledglings produced annually with age was partly
      explained by the disappearance of poor-quality members of the pairs, mainly poor
      quality males. Age-related breeding success (i.e. number of fledglings) was
      similar for barn swallows from Spain and Denmark. Therefore, the study of ageing
      patterns and life-history strategies in free-ranging animals from more than a
      single population can throw new light on life-history theory, population dynamics
      and evolutionary studies of senescence.

PMID- 22994535
TI  - Carfilzomib: in relapsed, or relapsed and refractory, multiple myeloma.
AB  - Intravenous carfilzomib is a peptide epoxyketone, next-generation proteasome
      inhibitor, which has been granted accelerated approval in the US for the
      treatment of patients with multiple myeloma who have received at least two prior
      therapies, including bortezomib and an immunomodulatory agent (thalidomide or
      lenalidomide), and have demonstrated disease progression on or within 60 days of
      completion of the last therapy. Carfilzomib displays high selectivity for and
      irreversibly inhibits the chymotrypsin-like catalytic activity of the 20S
      proteasome core particle, which results in cell growth arrest and apoptosis. In
      the pivotal, phase II, noncomparative trial in heavily pre-treated patients (n =
      266) with relapsed and refractory multiple myeloma, intravenous carfilzomib
      administered in 28-day cycles for up to 12 cycles produced an overall response
      rate of 23.7% in the response-evaluable population. The median duration of
      response was 7.8 months, the median progression-free survival was 3.7 months and
      the median overall survival was 15.6 months. Carfilzomib had an acceptable
      tolerability profile in patients with relapsed, or relapsed and refractory,
      multiple myeloma. There was a low incidence of grade 3 or higher peripheral
      neuropathy.

PMID- 22994536
TI  - Ferumoxytol: in iron deficiency anaemia in adults with chronic kidney disease.
AB  - Ferumoxytol is an intravenously administered iron preparation indicated in the EU
      and the US for the treatment of iron deficiency anaemia in adult patients with
      chronic kidney disease (CKD). It consists of superparamagnetic iron oxide
      nanoparticles coated with a semi-synthetic carbohydrate shell in an isotonic,
      neutral pH solution that can be administered at relatively high dose by rapid
      intravenous injection. In phase III, randomized, controlled trials, two doses of
      ferumoxytol (510 mg iron/dose) given 2-8 days apart increased mean haemoglobin
      levels from baseline to week 5 significantly more than oral iron (200 mg/day for
      21 days) in adult patients with iron deficiency anaemia and CKD stages 1-5.
      Ferumoxytol was more effective than oral iron both in patients with non-dialysis
      dependent CKD and in those with haemodialysis-dependent CKD. Ferumoxytol was
      generally well tolerated in randomized controlled clinical trials. Most adverse
      events were mild or moderate in intensity; serious hypersensitivity or
      hypotensive reactions were uncommon. Local injection-site reactions were the most
      common system/organ-class adverse events in a pooled analysis of clinical studies
      and post-marketing experience.

PMID- 22994538
TI  - Preliminary studies on the development of IgA-loaded chitosan-dextran sulphate
      nanoparticles as a potential nasal delivery system for protein antigens.
AB  - This study describes the development of a biodegradable nanoparticulate system
      for the intranasal delivery of multiple proteins. Chitosan (CS)-dextran sulphate
      (DS) nanoparticles were developed and optimised for the incorporation of
      pertussis toxin (PTX) and a potential targeting ligand (immunoglobulin-A, IgA).
      In vitro characterization and in vivo uptake studies were performed for the
      evaluation of developed nanoparticles. The ratio of CS to DS, the order of mixing
      and pH of nanoparticle suspension were identified as important formulation
      factors governing the size and zeta potential of nanoparticles. An optimised CS
      DS nanoparticle formulation prepared with the CS to DS weight ratio of 3 : 1 was
      used to load PTX and/or IgA. Entrapment efficiency of >90% was obtained for both.
      The in vivo uptake of IgA-loaded CS-DS nanoparticles in mice showed a
      preferential uptake of nanoparticles probably by nasal membranous or microfold
      cells following intranasal administration. The results of this study indicate the
      potential application of IgA-loaded CS-DS nanoparticles as a nasal vaccine
      delivery system.

PMID- 22994537
TI  - Adjuvant therapy for high-risk gastrointestinal stromal tumour: considerations
      for optimal management.
AB  - One randomized trial has found that adjuvant treatment with imatinib for
      gastrointestinal stromal tumour (GIST) 3 cm or larger in diameter prolongs
      recurrence-free survival, and another trial has reported that 3 years of adjuvant
      imatinib improves both recurrence-free and overall survival compared with 1 year
      of imatinib in high-risk GIST. The US National Comprehensive Cancer Network now
      recommends consideration of adjuvant imatinib for at least 3 years for patients
      with a high risk of GIST recurrence. Estimation of the risk of GIST recurrence is
      mandatory when considering adjuvant therapy. The risk varies greatly from
      negligible risk (tumours smaller than 1 cm) to 90% or greater risk (large tumours
      with frequent mitoses). The risk of recurrence can be estimated using one of the
      three validated risk stratification schemes, the National Institutes of Health
      (NIH) consensus risk criteria, the Armed Forces Institute of Pathology criteria
      or the modified NIH criteria, which have roughly similar prognostic accuracy, or
      with nomograms or prognostic contour maps. Patients with an intermediate risk may
      pose a problem when considering adjuvant therapy because few research data are
      available. The decision about whether or not to treat these patients with
      adjuvant imatinib can be solved using the modified NIH risk stratification
      criteria, since, with these criteria, patients with intermediate risk have
      similar outcomes to those with low risk, leaving only patients with high risk for
      consideration of adjuvant therapy. Analysis of tumour tissue for KIT and PDGFRA
      mutations is recommended to exclude patients with imatinib-insensitive mutations
      from adjuvant therapy (notably patients with PDGFRA substitution mutation D842V),
      and those with neurofibromatosis-1-associated wild-type GIST. The standard daily
      dose of adjuvant imatinib is 400 mg, but it is unknown whether this dose is
      optimal. Some patients, such as those with KIT exon 9 mutation, might benefit
      from a higher dose. While the optimal duration of adjuvant therapy is also
      unknown, 3 years of adjuvant imatinib is currently a reasonable choice. Early
      detection and management of imatinib side effects is likely important for
      achieving high compliance. Repeat imaging of the abdomen with CT or MRI during
      adjuvant imatinib and after its completion is also likely to be beneficial, since
      most patients whose GIST recurs after adjuvant treatment respond to reinstitution
      of imatinib, and the presence of a small tumour burden when imatinib is
      reinstituted may reduce the likelihood of rapid emergence of a second mutation
      that confers imatinib resistance.

PMID- 22994539
TI  - New insights into the control of neurotrophic growth factor receptor signaling:
      implications for nervous system development and repair.
AB  - Neurotrophic growth factors control neuronal development by activating specific
      receptor tyrosine kinase positive signaling pathways, such as Ras-MAPK and PI3K
      Akt cascades. Once activated, neurotrophic factor receptors also trigger a
      cascade of molecular events, named negative receptor signaling, that restricts
      the intensity of the positive signals and modulates cellular behavior. Thus, to
      avoid signaling errors that ultimately could lead to aberrant neuronal physiology
      and disease, negative signaling mechanisms have evolved to ensure that suitable
      thresholds of neuronal stimulation are achieved and maintained during right
      periods of time. Recent findings have revealed that neurotrophic factor receptor
      signaling is tightly modulated through the coordinated action of many different
      protein regulators that limit or potentiate signal propagation in spatially and
      temporally controlled manners, acting at specific points after receptor
      engagement. In this review, we discuss progress in this field, highlighting the
      importance of these modulators in axonal growth, guidance, neural connectivity,
      and nervous system regeneration.

PMID- 22994540
TI  - Distribution of prosaposin mRNA in the central nervous system of the pigeon
      (Columba livia).
AB  - Bioassay and immunohistochemical studies have detected the presence of prosaposin
      in the central nervous system (CNS) of mammals. Here, first time, we have
      determined the partial cDNA sequence of pigeon prosaposin and mapped the
      distribution of its mRNA in the pigeon CNS. The predicted amino acid sequence of
      pigeon prosaposin showed 93 and 60% identity to chicken and human prosaposin,
      respectively. In situ hybridization, autoradiograms showed that the prosaposin
      mRNA expression was found in the olfactory bulb, prepiriform cortex, Wulst,
      mesopallium, nidopallium, hippocampal formation, thalamus, tuberis nucleus, pre
      tectal nucleus, nucleus mesencephalicus lateralis, pars dorsalis, nucleus isthmi,
      pars parvocellularis and magnocellularis, Edinger-Westphal nucleus, optic tectum,
      cerebellar cortex and nuclei, vestibular nuclei and gray matter of the spinal
      cord. These results suggest that the cDNA sequence of pigeon prosaposin is
      comparable to other vertebrates, and the general distribution pattern of
      prosaposin mRNA resembles those are found in mammals. 

PMID- 22994541
TI  - Organ donation: when should we consider intestinal donation.
AB  - Although more than 2300 intestinal transplantations (IT) have been performed
      worldwide, a description of intestinal donor criteria is still missing. This
      causes confusion among transplant coordinators, OPOs, physicians at intensive
      care unit and transplant surgeons. A Med-line search looking for publications
      about donor criteria or donor selection in human IT was performed in December
      2011. Retrospective analysis of 39 deceased donors from whom, in the period
      January 2006-December 2011, 20 isolated intestinal grafts and 19 multivisceral
      grafts were recovered and successfully transplanted. REVIEW OF THE LITERATURE:
      Among 3504 publications about IT, no study reported specifically about intestinal
      donor profile. The most commonly cited donor criterion was age, while all other
      criteria were inconsistently discussed. Based on the collected data, we suggest
      following inclusion criteria for donation of IT grafts: age 0-50 years, ICU-stay
      <1 week, no blunt abdominal trauma, most recent Sodium <155 mmol/l, no severe
      ongoing transfusion requirements, standard donor therapy including early enteral
      nutrition and a compatible donor-recipient size match. By providing simple
      criteria for intestinal donation from deceased donor, we may help to properly
      utilize the limited donor pool.

PMID- 22994542
TI  - Interfacial and fluorescence studies on stereoblock poly(N-isopropylacryl
      amide)s.
AB  - Aqueous solution and water-air interfacial properties of associative thermally
      responsive A-B-A stereoblock poly(N-isopropylacryl amide), PNIPAM, polymers were
      studied and compared to atactic PNIPAM. The A-B-A polymers consist of atactic
      PNIPAM as a hydrophilic block (either A or B) and a water-insoluble block of
      isotactic PNIPAM. The surface tensions of aqueous PNIPAM solutions were measured
      as a function of both temperature and concentration. The isotactic blocks did not
      have an effect on the surface activity of the solutions. Rheological measurements
      on the water-air interface showed that the aggregated PNIPAMs containing
      isotactic blocks increased the elasticity of the surface significantly as
      compared to the atactic reference upon heating. Two fluorescence probes, pyrene
      and (4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (4HP),
      added to the aqueous polymer solutions were concluded to reside in surroundings
      with lower polarity and increased microviscosity in cases when the polymers
      contained isotactic blocks, as compared to ordinary atactic polymers.

PMID- 22994543
TI  - Tauroursodeoxycholic acid affects PPARgamma and TLR4 in Steatotic liver
      transplantation.
AB  - Numerous steatotic livers are discarded for transplantation because of their poor
      tolerance to ischemia-reperfusion (I/R). We examined whether tauroursodeoxycholic
      acid (TUDCA), a known inhibitor of endoplasmic reticulum (ER) stress, protects
      steatotic and nonsteatotic liver grafts preserved during 6 h in University of
      Wisconsin (UW) solution and transplanted. The protective mechanisms of TUDCA were
      also examined. Neither unfolded protein response (UPR) induction nor ER stress
      was evidenced in steatotic and nonsteatotic liver grafts after 6 h in UW
      preservation solution. TUDCA only protected steatotic livers grafts and did so
      through a mechanism independent of ER stress. It reduced proliferator-activated
      receptor-gamma (PPARgamma) and damage. When PPARgamma was activated, TUDCA did
      not reduce damage. TUDCA, which inhibited PPARgamma, and the PPARgamma antagonist
      treatment up-regulated toll-like receptor 4 (TLR4), specifically the TIR domain
      containing adaptor inducing IFNbeta (TRIF) pathway. TLR4 agonist treatment
      reduced damage in steatotic liver grafts. When TLR4 action was inhibited,
      PPARgamma antagonists did not protect steatotic liver grafts. In conclusion,
      TUDCA reduced PPARgamma and this in turn up-regulated the TLR4 pathway, thus
      protecting steatotic liver grafts. TLR4 activating-based strategies could reduce
      the inherent risk of steatotic liver failure after transplantation.

PMID- 22994544
TI  - Oxidative DNA adducts detected in vitro from redox activity of cigarette smoke
      constituents.
AB  - Cigarette smoke contains a variety of carcinogens, cocarcinogens, mutagens, and
      tumor promoters. In addition to polycyclic aromatic carcinogens and tobacco
      specific nitrosamines, cigarette smoke also contains an abundance of catechols,
      aldehydes, and other constituents, which are DNA damaging directly or indirectly;
      therefore, they can also contribute to cigarette smoke-mediated carcinogenicity.
      In this study, we investigated the potential of cigarette smoke constituents to
      induce oxidative damage to DNA through their capacity to redox cycle. When DNA
      (300 MUg/mL) was incubated with cigarette smoke condensate (0.2 mg of tobacco
      particulate matter/mL) and CuCl(2) as a catalyst (50-100 MUM), a variety of
      oxidative DNA adducts were detected by (32)P-postlabeling/TLC. Of the total
      adduct burden (2114 +/- 419 adducts/10(6) nucleotides), over 40% of all adducts
      were attributed to the benchmark oxidative DNA lesion, 8-oxodeoxyguanosine (8
      oxodG). Adducts were formed dose dependently. Essentially, similar adduct
      profiles were obtained when cigarette smoke condensate was substituted with ortho
      and para-dihydroxybenzenes. Vehicle treatment with Cu(2+) or CSC alone did not
      induce any significant amount of oxidative DNA damage. Furthermore, coincubation
      of cigarette smoke condensate and ortho-dihydroxybenzene with DNA resulted in a
      higher amount of oxidative DNA adducts than obtained with the individual entity,
      suggesting that adducts presumably originated from catechols or catechol-like
      compounds in cigarette smoke condensate. Adducts resulting from both cigarette
      smoke condensate and pure dihydroxybenzenes were chromatographically identical to
      adducts formed by reaction of DNA with H(2)O(2), which is known to produce 8
      oxodG, and many other oxidative DNA adducts. When the cigarette smoke condensate
      DNA reaction was performed in the presence of ellagic acid, a known antioxidant,
      the adduct formation was inhibited dose dependently, further suggesting that
      adducts originated from oxidative pathway. Our data thus provide evidence of the
      capacity of catechols or catechol-like constituents in cigarette smoke to produce
      oxidative DNA damage, which may contribute to the tumor-promoting activity of
      cigarette smoke.

PMID- 22994545
TI  - Bactericidal action of photoirradiated gallic acid via reactive oxygen species
      formation.
AB  - It is known that gallic acid shows antimicrobial activity. In the present study,
      photoirradiation induced reactive oxygen species formation was investigated for
      augmentation of the antimicrobial activity of gallic acid. Staphylococcus aureus
      suspended in 4 mmol/L gallic acid was exposed to blue light of a LED at 400 nm.
      This treatment killed the bacteria, and a >5-log reduction of the viable counts
      was observed within 15 min. By contrast, neither the LED treatment alone nor the
      treatment with gallic acid alone showed substantial bactericidal effect. When
      hydroxyl radical scavengers were added to the suspension, the bactericidal effect
      of photoirradiated gallic acid was attenuated. Furthermore, electron spin
      resonance analysis demonstrated that hydroxyl radicals were generated by the
      photoirradiation of gallic acid. Thus, the present study suggests that the photo
      oxidation can enhance the antimicrobial activity of gallic acid via hydroxyl
      radical formation. 

PMID- 22994546
TI  - Why optometry must work from urban and regional Aboriginal Health Services.
AB  - The gap in vision and ocular health between Aboriginal and Torres Strait Islander
      Australians and other Australians continues to be significant, yet three-quarters
      of the identified Aboriginal and Torres Strait Islander population live in urban
      and regional areas of Australia where existing eye-care services are available.
      In urban Australia, an improvement in the access and use of eye-health services
      is required to provide equitable eye-care outcomes for Australia's Indigenous
      peoples. Optometric services need to be available within Aboriginal Health
      Services in urban areas to effectively close the gap for vision.

PMID- 22994547
TI  - The juvenile hormone signaling pathway in insect development.
AB  - The molecular action of juvenile hormone (JH), a regulator of vital importance to
      insects, was until recently regarded as a mystery. The past few years have seen
      an explosion of studies of JH signaling, sparked by a finding that a JH
      resistance gene, Methoprene-tolerant (Met), plays a critical role in insect
      metamorphosis. Here, we summarize the recently acquired knowledge on the capacity
      of Met to bind JH, which has been mapped to a particular ligand-binding domain,
      thus establishing this bHLH-PAS protein as a novel type of an intracellular
      hormone receptor. Next, we consider the significance of JH-dependent interactions
      of Met with other transcription factors and signaling pathways. We examine the
      regulation and biological roles of genes acting downstream of JH and Met in
      insect metamorphosis. Finally, we discuss the current gaps in our understanding
      of JH action and outline directions for future research.

PMID- 22994548
TI  - Red turpentine beetle: innocuous native becomes invasive tree killer in China.
AB  - The red turpentine beetle (RTB), Dendroctonus valens LeConte (Coleoptera:
      Curculionidae: Scolytinae), is a secondary pest of pines in its native range in
      North and Central America. Outbreaks and tree mortality attributed to RTB alone
      are rare in its native range. RTB was introduced into China in the early 1980s
      and spread rapidly from Shanxi Province to four adjacent provinces; it has
      infested over 500,000 ha of pine forest and has caused extensive tree mortality
      since 1999. We provide a historical background on RTB outbreaks, explanations for
      its invasive success, management options, and economic impacts of RTB in China.
      Genetic variation in RTB fungal associates, interactions between RTB and its
      associated fungi, behavioral differences in Chinese RTB, and other factors
      favoring RTB outbreaks are considered in an effort to explain the invasiveness of
      RTB in China. The promise of semiochemicals as a management tool is also
      discussed.

PMID- 22994550
TI  - The relationship between placebo alcohol and affect: motives for drinking.
AB  - INTRODUCTION AND AIMS: Although alcohol is often used in an attempt to alleviate
      negative affect, alcohol oftentimes exacerbates depressive symptoms. Therefore
      the relationship between alcohol and affect, and the role of motives for drinking
      remain unclear. The present study hypothesised that placebo alcohol would blunt
      affective responding and that desire to drink would increase in individuals who
      expected alcohol to help them cope after a negative experience. The present study
      also explored whether motives and reasons for drinking altered after a negative
      experience. DESIGN AND METHODS: Participants (36 first-year psychology students
      and 41 community members) were randomly assigned to one of four experimental
      groups, being soft drink or placebo alcohol, neutral or negative mood induction.
      RESULTS: Two repeated measures analyses indicated that placebo alcohol did not
      significantly blunt affective responding after the negative mood induction. T
      tests showed that desire to drink did not significantly increase post negative
      mood induction for participants who endorsed coping motives for drinking.
      However, interestingly coping-depression and enhancement motives decreased after
      negative mood induction, and participants misattributed the majority of their
      mood to other life events. DISCUSSION AND CONCLUSIONS: The findings indicate that
      motives for drinking are amendable with prior learning, providing support for
      expectancy challenge procedures. The study also provides some evidence for
      alcohol's effect on emotional lability.

PMID- 22994549
TI  - Whole transcriptome analysis of the silicon response of the diatom Thalassiosira
      pseudonana.
AB  - BACKGROUND: Silicon plays important biological roles, but the mechanisms of
      cellular responses to silicon are poorly understood. We report the first analysis
      of cell cycle arrest and recovery from silicon starvation in the diatom
      Thalassiosira pseudonana using whole genome microarrays. RESULTS: Three known
      responses to silicon were examined, 1) silicified cell wall synthesis, 2)
      recovery from silicon starvation, and 3) co-regulation with silicon transporter
      (SIT) genes. In terms of diatom cell wall formation, thus far only cell surface
      proteins and proteins tightly associated with silica have been characterized. Our
      analysis has identified new genes potentially involved in silica formation, and
      other genes potentially involved in signaling, trafficking, protein degradation,
      glycosylation and transport, which provides a larger-scale picture of the
      processes involved. During silicon starvation, an overrepresentation of
      transcription and translation related genes were up-regulated, indicating that T.
      pseudonana is poised to rapidly recover from silicon starvation and resume cell
      cycle progression upon silicon replenishment. This is in contrast to other types
      of limitation, and provides the first molecular data explaining the well
      established environmental response of diatoms to grow as blooms and to out
      compete other classes of microalgae for growth. Comparison of our data with a
      previous diatom cell cycle analysis indicates that assignment of the cell cycle
      specific stage of particular cyclins and cyclin dependent kinases should be re
      evaluated. Finally, genes co-varying in expression with the SITs enabled
      identification of a new class of diatom-specific proteins containing a unique
      domain, and a putative silicon efflux protein. CONCLUSIONS: Analysis of the T.
      pseudonana microarray data has provided a wealth of new genes to investigate
      previously uncharacterized cellular phenomenon related to silicon metabolism,
      silicon's interaction with cellular components, and environmental responses to
      silicon.

PMID- 22994551
TI  - Neurosyphilis with dementia and bilateral hippocampal atrophy on brain magnetic
      resonance imaging.
AB  - BACKGROUND: This article reports a rare case of active neurosyphilis in a man
      with mild to moderate dementia and marked hippocampal atrophy, mimicking early
      onset Alzheimer's disease. Few cases have so far described bilateral hippocampal
      atrophy mimicking Alzheimer's disease in neurosyphilis. CASE PRESENTATION: The
      patient presented here is a 33 year old Bulgarian male, whose clinical features
      include progressive cognitive decline and behavioral changes over the last 18
      months. Neuropsychological examination revealed mild to moderate dementia (Mini
      Mental State Examination score was 16/30) with impaired memory and attention, and
      executive dysfunction. Pyramidal, and extrapyramidal signs, as well as dysarthria
      and impairment in coordination, were documented. Brain magnetic resonance imaging
      showed cortical atrophy with noticeable bilateral hippocampal atrophy. The
      diagnosis of active neurosyphilis was based on positive results of the Venereal
      Disease Research Laboratory test/Treponema pallidum hemagglutination reactions in
      blood and cerebrospinal fluid samples. In addition, cerebrospinal fluid analysis
      showed pleocytosis and elevated protein levels. High-dose intravenous penicillin
      therapy was administered. At 6 month follow up, improvements were noted
      clinically, on neuropsychological examinations, and in cerebrospinal fluid
      samples. CONCLUSION: This case underlines the importance of early diagnosis of
      neurosyphilis. The results suggest that neurosyphilis should be considered when
      magnetic resonance imaging results indicate mesiotemporal abnormalities and
      hippocampal atrophy. Neurosyphilis is a treatable condition which requires early
      aggressive antibiotic therapy.

PMID- 22994552
TI  - Maternal variation in EPHX1, a xenobiotic metabolism gene, is associated with
      childhood medulloblastoma: an exploratory case-parent triad study.
AB  - Common epidemiologic study designs used for evaluating germline genetic
      determinants of childhood medulloblastoma are often subject to population
      stratification bias and do not account for maternal genetic effects, a proxy for
      the intrauterine environment, which may be important in determining etiologic
      factors for this outcome. The case-parent triad design overcomes these
      limitations. Therefore, we conducted an exploratory study among 27 childhood
      medulloblastoma case-parent triads recruited from the Childhood Cancer
      Epidemiology and Prevention Center at Texas Children's Hospital (Houston, USA)
      between 2003 and 2010. We assessed 13 single nucleotide polymorphisms (SNPs) in
      nine xenobiotic detoxification genes, as deficiencies in this pathway may induce
      brain tumorigenesis. Log-linear modeling was used to assess the association
      between medulloblastoma and both the offspring (i.e., case) and maternal
      genotypes of each SNP. In our population, there were no offspring genotypes that
      were significantly associated with disease risk. However, the maternal EPHX1
      rs1051740 genotype (RR = 3.26, P = .01) was associated with medulloblastoma risk.
      This exploratory study highlights the utility of the case-parent triad design,
      but these results should be interpreted cautiously due to the limited sample
      size.

PMID- 22994555
TI  - CaWRKY40, a WRKY protein of pepper, plays an important role in the regulation of
      tolerance to heat stress and resistance to Ralstonia solanacearum infection.
AB  - WRKY proteins form a large family of plant transcription factors implicated in
      the modulation of numerous biological processes, such as growth, development and
      responses to various environmental stresses. However, the roles of the majority
      WRKY family members, especially in non-model plants, remain poorly understood. We
      identified CaWRKY40 from pepper. Transient expression in onion epidermal cells
      showed that CaWRKY40 can be targeted to nuclei and activates expression of a W
      box-containing reporter gene. CaWRKY40 transcripts are induced in pepper by
      Ralstonia solanacearum and heat shock. To assess roles of CaWRKY40 in plant
      stress responses we performed gain- and loss-of-function experiments.
      Overexpression of CaWRKY40 enhanced resistance to R. solanacearum and tolerance
      to heat shock in tobacco. In contrast, silencing of CaWRKY40 enhanced
      susceptibility to R. solanacearum and impaired thermotolerance in pepper.
      Consistent with its role in multiple stress responses, we found CaWRKY40
      transcripts to be induced by signalling mechanisms mediated by the stress
      hormones salicylic acid (SA), jasmonic acid (JA) and ethylene (ET).
      Overexpression of CaWRKY40 in tobacco modified the expression of hypersensitive
      response (HR)-associated and pathogenesis-related genes. Collectively, our
      results suggest that CaWRKY40 orthologs are regulated by SA, JA and ET signalling
      and coordinate responses to R. solanacearum attacks and heat stress in pepper and
      tobacco.

PMID- 22994556
TI  - Predictors of symptomatic HIV-associated neurocognitive disorders in universal
      health care.
AB  - OBJECTIVES: The aim of the study was to determine the risk factors predictive of
      symptomatic HIV-associated neurocognitive disorders (sHAND) among HIV-infected
      patients receiving active medical care. METHODS: Baseline demographic and
      clinical characteristics were analysed in patients with sHAND (HIV-associated
      dementia and minor neurocognitive disorder) in a population-based longitudinal
      cohort of HIV-infected patients with access to universal health care, including
      combination antiretroviral therapy (cART) from 1999 to 2008. Variables evaluated
      for their association with sHAND included age and ethnicity, survival duration
      with HIV-1 infection, vascular disease risk factors, and laboratory indices such
      as blood CD4 T-cell count at its nadir and at cART initiation, using both
      univariable and multivariable logistic regression models. RESULTS: A total of
      1320 patients were investigated, including the patients diagnosed with sHAND (n =
      90) during the study period. In univariable analyses, increased age, increased
      length of survival with HIV, low nadir CD4 and CD8 T-cell counts, high baseline
      viral load (> 1,000,000 HIV-1 RNA copies/mL), and African origin were predictive
      of a diagnosis of sHAND (P < 0.05). In multivariable analysis, increased age,
      increased length of survival, low nadir CD4 T-cell counts, and high baseline
      viral load remained predictive of sHAND (P < 0.05). Remarkably, CD4 T-cell counts
      at cART initiation, hepatitis C virus coinfection, and vascular disease risk
      factors failed to predict sHAND in both analyses. CONCLUSIONS: Increased age and
      survival duration, lower nadir CD4 T-cell counts, and higher baseline viral load
      were consistent predictors of the development of sHAND among persons with
      HIV/AIDS in universal health care, underscoring the importance of attention to
      these variables in clinical care.

PMID- 22994554
TI  - Aerobic exercise reduces oxidative stress and improves vascular changes of small
      mesenteric and coronary arteries in hypertension.
AB  - BACKGROUND AND PURPOSE: Regular physical activity is an effective non
      pharmacological therapy for prevention and control of hypertension. We
      investigated the effects of aerobic exercise training in vascular remodelling and
      in the mechanical and functional alterations of coronary and small mesenteric
      arteries from spontaneously hypertensive rats (SHR). EXPERIMENTAL APPROACH:
      Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks
      were used to evaluate vascular structural, mechanical and functional properties.
      KEY RESULTS: Exercise did not affect lumen diameter, wall thickness and
      wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric
      arteries from SHR. Exercise also reduced collagen deposition and normalized
      altered internal elastic lamina organization and expression of MMP-9 in
      mesenteric arteries from SHR. Exercise did not affect contractile responses of
      coronary arteries but improved the endothelium-dependent relaxation in SHR. In
      mesenteric arteries, training normalized the increased contractile responses
      induced by U46619 and by high concentrations of acetylcholine. In vessels from
      SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and
      the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized
      the increased O(2) (-)  production and the reduced Cu/Zn superoxide dismutase
      expression and increased NO production. CONCLUSIONS AND IMPLICATIONS: Exercise
      training of SHR improves endothelial function and vascular stiffness in coronary
      and small mesenteric arteries. This might be related to the concomitant decrease
      of oxidative stress and increase of NO bioavailability. Such effects demonstrate
      the beneficial effects of exercise on the vascular system and could contribute to
      a reduction in blood pressure.

PMID- 22994557
TI  - Scope of the two-step, one-pot palladium-catalyzed borylation/Suzuki cross
      coupling reaction utilizing bis-boronic acid.
AB  - The use of bis-boronic acid for the direct synthesis of boronic acids has greatly
      facilitated the two-step, one-pot borylation/Suzuki cross-coupling reaction
      between aryl and heteroaryl halides. With use of Buchwald's second-generation
      XPhos preformed catalyst, high yields of cross-coupled products were obtained for
      most substrates. The method also allows an efficient two-step, one-pot synthesis,
      providing access to three distinct cross-coupled products after column
      chromatography. The method also provides a rapid and convenient route to teraryl
      compounds.

PMID- 22994558
TI  - Uptake of oxytetracycline, sulfamethoxazole and ketoconazole from fertilised
      soils by plants.
AB  - This study was performed to investigate the potential for a set of two
      antibiotics and one antifungal compound to be taken up from the soil by plants.
      Plants are used for animal or human consumption, and so the measured
      concentrations in the plant material will be used to model potential human
      exposure to these compounds. The uptake by two types of plants (grass and
      watercress) from two types of soil was studied. The compounds used for these
      experiments were sulfamethoxazole, oxytetracycline and ketoconazole at
      concentrations of 5 and 10 mg kg(-1) in the soil. The compounds of interest were
      extracted out of the plant matrix by applying accelerated solvent extraction.
      Analyses were carried out by a LC-MS/MS. From the results, it was concluded that
      the plant materials used for this study were able to take up sulfamethoxazole and
      ketoconazole when the soil was contaminated with these compounds at a
      concentration ranging from 5 to 10 mg kg(-1). Sulfamethoxazole was detected in
      all samples, at levels ranging from 7 to 21 u kg(-1) for grass and 4 to 7.5 u kg(
      1) for watercress. For ketoconazole, the results showed low absorption.
      Oxytetracycline was not detected in any sample. A partition-limited model
      approach was applied for the comparison of experimental and estimated data, and
      the relationship between physicochemical properties of the compounds and plant
      uptake was highlighted. 

PMID- 22994559
TI  - Antimicrobial prescribing practice in UK equine veterinary practice.
AB  - REASONS FOR PERFORMING STUDY: Antimicrobial use is known to select for the
      emergence of resistant strains of bacteria; therefore prudent use in both human
      and veterinary medicine is essential to preserve their efficacy. OBJECTIVES: To
      characterise antimicrobial prescribing patterns in UK equine practice and
      evaluate factors associated with prescribing. METHODS: A postal questionnaire
      including 4 clinical scenarios was sent to 740 veterinary surgeons that treat
      horses. Data were collected on the clinician, their practice and sources of
      information regarding antimicrobials and their use. Multivariable logistic
      regression analysis was used to ascertain factors associated with 5 outcomes;
      prescribing off-licence drugs; prescribing at incorrect doses; prescribing 3rd or
      4th generation cephalosporins; prescribing fluoroquinolones and prescribing
      potentiated sulphonamides. RESULTS: Questionnaires were completed by 38% of
      veterinary surgeons who were sent questionnaires. Less than 1% of practices had
      antimicrobial use guidelines. Trimethoprim-sulphonamides were most commonly
      prescribed in each clinical scenario. Eleven percent of prescriptions were for
      antimicrobial drugs not licensed for use in horses in the UK. Five percent of
      prescriptions for licensed antimicrobials were under the recommended dose rate
      and 56% over the recommended dose rate. Fluoroquinolones and 3rd and 4th
      generation cephalosporins accounted for 1 and 3% of prescriptions, respectively.
      Veterinary surgeons working at referral practices were more likely to prescribe
      3rd and 4th generation cephalosporins and fluoroquinolones and off-licence
      antimicrobials whereas those working in first-opinion practices were more likely
      to prescribe potentiated sulphonamides. Sources of information regarding
      antimicrobials also had an effect on prescribing. CONCLUSIONS AND POTENTIAL
      RELEVANCE: Prescription of antimicrobials at inappropriate doses was common even
      when provided with the weight of the animal. It is uncommon for UK equine
      veterinary practices to have guidelines for antimicrobial use. The introduction
      of such guidelines could lead to more prudent use of antimicrobials.

PMID- 22994560
TI  - Localized deoxygenation and direct patterning of graphene oxide films by focused
      ion beams.
AB  - Exposure to controlled doses (~4.65 * 10(-3) to 2.79 * 10(-2) nC/MUm(2) ion
      fluence) of Ga ions via a focused ion beam (FIB) deoxygenates graphene oxide (GO)
      and increases the electrical conductivity in 100 * 100 MUm(2) patches by several
      orders of magnitude compared to that in unexposed GO. Raman spectra and the
      carbon/oxygen ratio in exposed areas are indicative of chemically reduced
      graphene oxide (rGO). This novel FIB-induced conversion technique is harnessed
      for the direct imprinting of complex micrometer-scale shapes and sub-20-nm lines
      of rGO in insulating films and flakes of GO establishing the capability of
      generating features varying in size from approximately tens of nanometers to
      approximately hundreds of micrometers in a maskless, efficient manner.

PMID- 22994561
TI  - Ethical issues related to screening for preeclampsia.
AB  - The implementation of new methods of treating and preventing disease raises many
      question of both technical and moral character. Currently, many studies focus on
      developing a screening test for preeclampsia (PE), a disease complicating 2-8% of
      pregnancies, potentially causing severe consequences for pregnant women and their
      fetuses. The purpose is to develop a test that can identify pregnancies at high
      risk for developing PE sufficiently early in pregnancy to allow for prophylaxis.
      However, the question of implementing a screening test for PE does not only
      involve an evaluation of technical feasibility and clinical efficacy, it also
      requires an analysis of how the test influences the conditions and choices for
      those tested. This study evaluates state-of-the-art techniques for preeclampsia
      screening in an ethical framework, pointing out the central areas of moral
      relevance within the context of such screening activity. Furthermore, we propose
      ethical guidelines that a screening programme for PE should meet in order to
      become an uncontroversial addition to prenatal health care. 

PMID- 22994562
TI  - Does competition drive character differences between species on a
      macroevolutionary scale?
AB  - Sympatric sister species generally have a degree of phenotypic differentiation
      that allows them to coexist. It has been well documented that phenotypic
      similarity results, through resource competition, in one of two major outcomes:
      local extinction of either competitor or character displacement. Limiting
      similarity suggests that there is a maximum degree of phenotypic niche overlap
      with which similar species may coexist. Breaching that maximum would result in
      exclusion. Character displacement, on the other hand, implies that the species
      differentiate phenotypically so that resource competition is reduced to the point
      where coexistence is possible. While it has been suggested that these theories
      have the potential to accelerate (character displacement) or limit phenotypic
      evolution (competitive exclusion) on microevolutionary time scales, their effects
      on macroevolution remain under-studied. If competition accelerates evolution on a
      macroevolutionary scale, one would expect that phenotypic diversity increases as
      novel species 'push aside' existing species. On the other hand, one might also
      expect that phenotypic evolution comes to a halt as novel species are trapped in
      the (ever decreasing) phenotypic space not yet occupied by existing species,
      except at the extremes of the phenotypic spectrum. Studying the current
      geographical ranges of more than 3000 extant species representing 29 mammalian
      families and their respective body masses, I found little evidence of competition
      accelerating body size differentiation between species.

PMID- 22994563
TI  - A complex of synaptic adhesion molecule CADM1, a molecule related to autism
      spectrum disorder, with MUPP1 in the cerebellum.
AB  - Mutations in the synaptic adhesion protein CADM1 (RA175/SynCAM1) are associated
      with autism spectrum disorder (ASD), a neurodevelopmental disorder of uncertain
      molecular origin. Cadm1-knock out (KO) mice exhibit smaller cerebella with
      decreased number of synapse of Purkinje cells and some ASD-like symptoms,
      including impaired ultrasonic vocalization. In this study, we examined the
      alteration of the Cadm1 synaptic complex in the mouse cerebellum at post-natal
      stages. The C-terminal peptide of Cadm1 associated with Mupp1 at PSD-95/Dlg/ZO-1
      (PDZ)(1-5), a scaffold protein containing 13 PDZ domains, which interacted with
      gamma-aminobutyric acid type B receptor (GABBR)2 at PDZ13, but not with PSD-95.
      The GABBR2 was detected in a set of proteins interacting with Cadm1 C-terminal.
      Cadm1 colocalized with Mupp1 and GABBR2 on the dendrites of Purkinje cells in the
      molecular layers of the developing cerebellum and on the dendrites of hippocampal
      neurons cultured in vitro. These observations suggest that the Cadm1 synaptic
      receptor complex, including Mupp1-GABBR2, is located on the dendrites of Purkinje
      cells. The amount of GABBR2 protein, but not mRNA, was increased in the cerebella
      of Cadm1 KO mice, suggesting that lack of Cadm1 does not affect transcription of
      GABBR2, but may stabilize the Mupp1-GABBR2 complex; the Mupp1-GABBR2 interaction
      may be stabilized by conformational change in Mupp1 or association with other
      adhesion molecules and by anchorage to the post-synaptic membrane. Up-regulation
      of GABBR2 in the cerebellum in the absence of CADM1 may be associated with ASD
      pathogenesis.

PMID- 22994564
TI  - Stereotactic body radiotherapy for prostate cancer: a preliminary report.
AB  - AIMS: We report the results of a retrospective study of stereotactic body
      radiotherapy (SBRT) using a Cyberknife for prostate cancer. METHODS: In all 29
      patients were treated with hypofractionated SBRT using a Cyberknife at median 36
      Gy in five fractions. All the patients were treated with a radical aim. Prostate
      specific antigen (PSA) was evaluated at baseline and after radiotherapy. Acute
      (<=3 months) and late (>3 months) urinary and rectal toxicities were recorded
      according to the CTCAE version 4.0. RESULTS: The median duration of follow up was
      41 months. PSA values decreased in a time-dependent way. The median PSA nadir was
      0.329 ng/mL, achieved after a median of 23 months' follow up. Two patients had a
      PSA failure according to the definition of nadir + 2 ng/mL. Eight patients (28%)
      had a benign PSA bounce at median 9 months after radiotherapy. CTCAE Grade 2 and
      3 late urinary toxicities were reported in 3 and 3%, respectively. One patient
      had exacerbated urinary symptoms and received an operation. There were no severe
      late rectal toxicities. CONCLUSIONS: The preliminary findings of our study
      suggest SBRT is feasible for prostate cancer treatment. Further studies with more
      patients and longer follow-up duration are required.

PMID- 22994566
TI  - Improving chronic lung disease management in rural and remote Australia: the
      Breathe Easy Walk Easy programme.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the impact of a chronic lung disease
      management training programme, Breathe Easy Walk Easy (BEWE), for rural and
      remote health-care practitioners. METHODS: Quasi-experimental, before and after
      repeated measures design. Health-care practitioners (n = 33) from various
      professional backgrounds who attended the BEWE training workshop were eligible to
      participate. Breathe Easy Walk Easy, an interactive educational programme,
      consisted of a training workshop, access to online resources, provision of
      community awareness-raising materials and ongoing telephone/email support.
      Participant confidence, knowledge and attitudes were assessed via anonymous
      questionnaire before, immediately after and at 3 and 12 months following the BEWE
      workshop. At 12 months, local provision of pulmonary rehabilitation services and
      patient outcome data (6-min walk test results before and after pulmonary
      rehabilitation) were also recorded. RESULTS: Measured knowledge (score out of 19)
      improved significantly after the workshop (mean difference 7.6 correct answers,
      95% confidence interval: 5.8-9.3). Participants' self-rated confidence and
      knowledge also increased. At 12-month follow up, three locally run pulmonary
      rehabilitation programmes had been established. For completing patients, there
      was a significant increase in 6-min walk distance following rehabilitation of 48
      m (95% confidence interval: 18-70 m). CONCLUSIONS: The BEWE programme increased
      rural and remote health-care practitioner knowledge and confidence in delivering
      management for people living with chronic lung disease and facilitated the
      establishment of effective pulmonary rehabilitation programmes in regional and
      remote Australian settings where access to such programmes is limited.

PMID- 22994565
TI  - Accurate variant detection across non-amplified and whole genome amplified DNA
      using targeted next generation sequencing.
AB  - BACKGROUND: Many hypothesis-driven genetic studies require the ability to
      comprehensively and efficiently target specific regions of the genome to detect
      sequence variations. Often, sample availability is limited requiring the use of
      whole genome amplification (WGA). We evaluated a high-throughput microdroplet
      based PCR approach in combination with next generation sequencing (NGS) to target
      384 discrete exons from 373 genes involved in cancer. In our evaluation, we
      compared the performance of six non-amplified gDNA samples from two HapMap family
      trios. Three of these samples were also preamplified by WGA and evaluated. We
      tested sample pooling or multiplexing strategies at different stages of the
      tested targeted NGS (T-NGS) workflow. RESULTS: The results demonstrated
      comparable sequence performance between non-amplified and preamplified samples
      and between different indexing strategies [sequence specificity of 66.0% +/-
      3.4%, uniformity (coverage at 0.2* of the mean) of 85.6% +/- 0.6%]. The average
      genotype concordance maintained across all the samples was 99.5% +/- 0.4%,
      regardless of sample type or pooling strategy. We did not detect any errors in
      the Mendelian patterns of inheritance of genotypes between the parents and
      offspring within each trio. We also demonstrated the ability to detect minor
      allele frequencies within the pooled samples that conform to predicted models.
      CONCLUSION: Our described PCR-based sample multiplex approach and the ability to
      use WGA material for NGS may enable researchers to perform deep resequencing
      studies and explore variants at very low frequencies and cost.

PMID- 22994567
TI  - Twelve tips for developing a near-peer shadowing program to prepare students for
      clinical training.
AB  - BACKGROUND: One effective way to help prepare medical students for clinical
      training is the implementation of a near-peer shadowing program, in which pre
      clinical trainees shadow clinical trainees. AIMS: This article describes
      techniques for ensuring the effectiveness of a near-peer shadowing program in the
      hope of improving the preparedness of students for clinical training. METHOD: A
      list of 12 tips were developed by combining a review of the literature with a
      reflection upon the authors' own experiences with developing a near-peer
      shadowing program, in which first-year medical students shadowed first-year
      residents. RESULTS: Both successes and failures were identified, both in the
      literature and in the author's own experiences. These can be used to inform the
      development of future programs. CONCLUSIONS: A near-peer shadowing program has
      the strong potential to play a key role in preparing students to enter clinical
      training. These 12 tips, drawn from the literature and our own experience, will
      maximize the benefits for both student and tutor learning and minimize the
      potential pitfalls encountered by other programs.

PMID- 22994568
TI  - Challenges in communication during clerkships: a case report.
AB  - Patient-centered communication skills training is an integral part of the medical
      training of students of the Radboud University Nijmegen Medical Centre. During
      their clerkships, however, students are confronted with a variety of physicians,
      demonstrating communication skills which differ from what they have been taught.
      Some physicians have difficulty with patient-centered communication themselves.
      This may cause students to adopt inadequate communication behaviors. To prevent
      this, we suggest raising awareness in students and including supervising
      physicians in communication skills training.

PMID- 22994569
TI  - Plasma adiponectin before and after kidney transplantation.
AB  - The role of plasma adiponectin (ADPN) in patients with impaired kidney function
      and following kidney transplantation (Tx) is debated. We aimed to: (i) determine
      whether pretransplant ADPN level is an independent risk factor for deterioration
      of glucose tolerance including development of new-onset diabetes mellitus after
      Tx, (ii) describe which parameters that influence the ADPN concentration before
      and after Tx. Fifty-seven nondiabetic kidney allograft recipients and 40
      nondiabetic uraemic patients were included. The Tx group was examined at baseline
      and 3 and 12 months after Tx. The uraemic control group was examined twice,
      separated by 12 months. ADPN levels declined significantly following Tx (P <
      0.0001), while estimated glomerular filtration rate (eGFR) increased (P <
      0.0005). eGFR, BMI and insulin sensitivity index were independently associated
      with ADPN in a multivariate regression analysis, whereas an ordinal logistic
      regression analysis revealed no predictive characteristic of ADPN for aggravation
      of the glucose tolerance after Tx. In conclusion, kidney transplantation is
      accompanied by a significant reduction in ADPN concentration. Several factors
      determine the ADPN concentration before and after Tx including kidney function,
      insulin resistance, use of immunosuppressive agents and BMI. Pretransplant ADPN
      level did not predict development of new-onset diabetes mellitus or even
      deterioration of the glucose tolerance following Tx.

PMID- 22994570
TI  - Second Symposium on Interdisciplinary Activities in Environmental Toxicology in
      North Rhine-Westphalia, Germany: part two.

PMID- 22994571
TI  - Analysis of ochratoxin A blood levels in bladder cancer cases and healthy persons
      from Pakistan.
AB  - The mycotoxin ochratoxin A (OTA), a well-known human nephrotoxic and carcinogenic
      agent, is a public health concern in many countries. Exposure is assessed by
      means of mycotoxin analysis in food commodities and by human biomonitoring of OTA
      in blood samples. Data available from several European countries and some studies
      in Africa, Asia, and the Americas indicate frequent detection of OTA. Thus far,
      data from developing countries that compare blood levels in healthy and diseased
      individuals are scarce. Thus, the aim of this investigation was to determine OTA
      levels in blood samples of bladder cancer patients (n = 96) and healthy controls
      (n = 31) from Pakistan. OTA in blood plasma was analyzed after extraction by high
      performance liquid chromatography (HPLC) with fluorescence detection. Among
      samples of 87 cancer patients and 30 controls, 92% in total contained
      quantifiable amounts of OTA. In bladder cancer cases the median OTA concentration
      was 0.19 ng/ml (mean 0.296; range: 0.03 to 3.41 ng/ml), and in healthy controls
      the median OTA was 0.19 ng/ml (mean 0.3; range: 0.04 to 1.24 ng/ml). The OTA
      levels found in the Pakistanian cohorts were comparable to those reported
      previously for the general population in the European Union. In conclusion, OTA
      is not likely to play a major role in the etiology of bladder cancer in the
      Karachi cohort, at least as the sole risk factor.

PMID- 22994572
TI  - Development and application of mold antigen-specific enzyme-linked immunosorbent
      assays (ELISA) to quantify airborne antigen exposure.
AB  - The aim of our study was to develop specific enzyme-linked immunosorbent assays
      (ELISAs) and apply these to assess mold antigen exposure in composting plants.
      Sandwich ELISAs based on polyclonal antibodies to Aspergillus fumigatus (Af),
      Penicillium chrysogenum (Pc), and Cladosporium herbarum (Ch) antigens were
      developed and validated. Reactivity to 18 different mold species was tested. To
      optimize extraction procedure, inhalable dust samples taken by a parallel sampler
      were extracted with or without homogenization. In 31 composting plants stationary
      pumps were installed at 4 sites to collect 124 inhalable dust samples. The newly
      developed ELISAs were used in addition to an anti beta-1,3-glucan ELISA to
      quantify mold antigens. The Cladosporium ELISA showed less than 0.04% reactivity
      to extracts from other fungal genera, while the Af ELISA demonstrated a
      reactivity of up to 3.6% and the Pc ELISA reacted up to 11% to other mold
      species. Extraction of parallel sampled filters gave higher antigen amounts with
      homogenization. The increase was highest for Pc-antigens, followed by Af
      antigens, and lowest for Ch-antigens. Mean lower detection limits of homogenized
      inhalable dust samples were 5 ng/m(3) (Af), 0.6 ng/m(3) (Pc), 0.2 ng/m(3) (Ch),
      and 0.6 ng/m(3) (beta-1,3-glucan). The ELISAs were able to detect antigens in 43%
      (Af), 37% (Pc), 94% (Ch), or 100% (beta-1,3-glucan) of the 124 airborne dust
      samples. Inhalable dust, beta-1,3-glucan, and Af-, Pc-, and Ch-antigen
      concentrations were significantly correlated. The newly developed mold antigen
      ELISAs are thus able to measure airborne exposure levels in composting plants and
      differentiate between distinct fungi genera.

PMID- 22994573
TI  - Effects of cigarette smoke condensate on primary urothelial cells in vitro.
AB  - Cigarette smoking is a risk factor for bladder cancer. Since urothelial cells
      express phase I and II enzymes these cells are able to metabolize precarcinogens
      into DNA reactive intermediates. Cigarette smoke is a complex mixture containing
      at least 80 known carcinogens. In this context especially aromatic amines and
      polycyclic aromatic hydrocarbons are discussed as being responsible for bladder
      carcinogenicity. Cell cultures of primary porcine urinary bladder epithelial
      cells (PUBEC) have been useful models for studies on bladder-specific effects.
      These cells are metabolically competent and found to be a valuable tool for
      examining effects of cigarette smoke constituents. In the present study PUBEC
      were utilized to investigate the effects of the complex mixture cigarette smoke
      condensate total particulate matter (CSC TPM) with emphasis on induction of
      cytochrome P-450 1A1 (CYP1A1) and genotoxic effects. CYP1A1 induction was
      investigated by Western blot and flow cytometry. The most pronounced effects were
      found after 24 h of incubation with 1-10 MUg/ml CSC TPM. Maximal induction was
      observed at 5 MUg/ml by flow cytometry and at 10 MUg/ml by Western blot analysis.
      Genotoxic effects were investigated by means of alkaline single-cell gel
      electrophoresis ("comet assay") with and without the use of the DNA repair enzyme
      formamidopyrimidine-DNA glycosylase (Fpg) and the micronucleus (MN) test. A
      numerical concentration-dependent increase in Fpg-sensitive sites indicating
      oxidative DNA damage and a quantitative rise in MN formation were noted. The CSC
      utilized in this study contained low amounts of benzo[a]pyrene, 4-aminobiphenyl,
      and 2-naphthylamine. With regard to the observed CYP1A1 induction, these
      substances cannot explain the CYP1A1 inducing effect of CSC TPM. It is possible
      that other compounds within CSC TPM contribute to CYP1A1 induction in our
      cellular model.

PMID- 22994574
TI  - N-Acetylation of p-aminobenzoic acid and p-phenylenediamine in primary porcine
      urinary bladder epithelial cells and in the human urothelial cell line 5637.
AB  - N-Acetyltransferases (NAT) are important enzymes in the metabolism of certain
      carcinogenic arylamines, as N-acetylation decreases or prevents their
      bioactivation via N-hydroxylation. To study such processes in the bladder, cell
      culture models may be used, but metabolic competence needs to be characterized.
      This study focused on the N-acetylation capacity of two urothelial cell systems,
      using p-aminobenzoic acid (PABA) and the hair dye precursor p-phenylenediamine
      (PPD), two well-known substrates of the enzyme NAT1. The constitutive NAT1
      activity was investigated using primary cultures of porcine urinary bladder
      epithelial cells (PUBEC) and in the human urothelial cell line 5637 to assess
      their suitability for further in vitro studies on PABA and PPD-induced toxicity.
      N-Acetylation of PABA and PPD was determined by high-performance liquid
      chromatography (HPLC) analysis in cytosols of the two cell systems upon
      incubation with various substrate levels for up to 60 min. The primary PUBEC
      revealed higher N-acetylation rates (2.5-fold for PABA, 5-fold for PPD) compared
      to the 5637 cell line, based on both PABA conversion to its acetylated metabolite
      and formation of mono- and diacetylated PPD. The urothelial cell systems may thus
      be useful as a tool for further studies on the N-acetylation of aromatic amines
      via NAT1.

PMID- 22994575
TI  - Bladder cancer survival in a former industrial area in Saxony-Anhalt, Germany.
AB  - Long-term follow-ups on bladder cancer patients from highly industrialized areas
      are rare. Therefore, we present a follow-up of bladder cancer patients from the
      greater area Lutherstadt Wittenberg, a center of the chemical industry of the
      former German Democratic Republic. Relapse-free survival times of 213 confirmed
      bladder cancer cases from the greater area Lutherstadt Wittenberg were collected
      between 2008 and 2009. Data on lifestyle and occupational exposure to potential
      carcinogens was recorded by questionnaire. Genotypes of N-acetyltransferase 2
      (NAT2), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1
      (GSTT1), rs710521, and rs9642880 were determined by standard methods. Cox models
      were used to evaluate differences in relapse-free survival. Clear differences in
      relapse-free survival could be observed for the number of relapses, multilocular
      tumor growth, and relapses with higher staging or grading than the primary tumor,
      as well as GSTT1. None of the other investigated polymorphisms showed significant
      impact on prognosis. This is the first study on two recently detected single
      nucleotide polymorphisms (SNPs) showing that these polymorphisms may also
      contribute to shorter relapse-free times.

PMID- 22994576
TI  - Cytotoxic potency of mycotoxins in cultures of V79 lung fibroblast cells.
AB  - In addition to dietary mycotoxin intake, exposure by inhalation is possible and
      may result in local effects in the lung. As a first approach to assess the
      potential local impact of inhaled mycotoxins, the cytotoxicity of 14 different
      mycotoxins was determined in V79 cell cultures, which served as an in vitro
      surrogate for lung cells. Cell viability was measured by the neutral red (NR)
      uptake assay after 48 h of exposure to graded concentrations of structurally
      diverse compounds: beauvericin, citrinin, enniatin B, moniliformin, ergocornine,
      ergotamine, fumonisin B1, ochratoxin A, patulin, the trichothecenes
      deoxynivalenol, HT-2, and T-2 toxin, and zearalenone, and alpha-zearalenol. The
      14 mycotoxins show a wide range of cytotoxic potency, encompassing 7 orders of
      magnitude, with IC(20) values (concentration reducing cell viability by 20%) of
      4.3 mM for moniliformin, the least potent mycotoxin, and 2.1 nM for T-2 toxin,
      the most potent agent. Thus, when inhaled in sufficient quantities, local adverse
      effects in lung cells cannot be excluded, in particular for highly cytotoxic
      mycotoxins.

PMID- 22994577
TI  - Prenatal and early life exposure to polychlorinated dibenzo-p-dioxins,
      dibenzofurans and biphenyls may influence dehydroepiandrosterone sulfate levels
      at prepubertal age: results from the Duisburg birth cohort study.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and polychlorinated
      biphenyls (PCB) are postulated to act as endocrine disrupters. In the ongoing
      Duisburg birth cohort study, started in 2000-2002, influence of persistent
      organic pollutants (POP) on child development was monitored. For the first time,
      associations were reported between prenatal and postnatal PCDD/F and PCB
      exposures and early endocrinological changes concerning adrenarchal development.
      PCDD/F and PCB concentrations were measured in blood samples taken in wk 32 of
      pregnancy and in breast milk using gas chromatography and high-resolution mass
      spectrometry (GC/HRMS). At the age of 6-7 and 8-9 yr, serum samples were
      collected from 111 children. The samples were assayed for the sex hormones
      testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), and 17-OH
      progesterone (17-OHP) by using an automated chemiluminescence assay system.
      Analyses of repeated measurements of DHEA-S serum levels were performed by linear
      regression analysis using generalized estimating equations (GEE). Linear
      regression analysis showed a positive association between DHEA-S and breast milk
      levels of PCDD/F and PCB expressed as toxicity equivalents according to toxicity
      equivalent factors published by the World Health Organization (WHO) in 2005
      (WHO(2005)-TEq) (increase of 29%, geometric mean ratio, GMR: 1.29, 95% CI 1.06-1.
      58 per doubling of PCDD/F + PCB WHO(2005)-TEq levels). Results for the
      association with the WHO(2005)-TEq levels in blood of mothers were in the same
      direction (increase of 15%, GMR 1.15, 95% CI 0.93-1.42 per doubling of PCDD/F +
      PCB WHO(2005)-TEq levels), but not significant. Data indicate that PCDD/F and PCB
      exposure in infancy may influence DHEA-S serum levels in prepubertal children.
      Increased DHEA-S serum levels are considered to indicate acceleration of the
      adrenal maturation.

PMID- 22994578
TI  - Surveillance program for former PCB-exposed workers of a transformer and
      capacitor recycling company, family members, employees of surrounding companies,
      and area residents--executive summary.
AB  - In a German company polychlorinated biphenyls (PCB)-containing transformers and
      capacitors were recycled on a large scale. Human biomonitoring revealed a high
      PCB body burden in workers of the recycling company, in surrounding locations of
      this plant, in companies in the neighborhood of this plant, and in family members
      of these employees. In order to clarify whether possible adverse health effects
      occurred or may occur in the future, a prospective surveillance program was
      initiated. After an extensive literature search, an interdisciplinary group of
      experts developed a surveillance program based on current knowledge with respect
      to possible adverse health effects that might occur in the recycling process of
      transformers and capacitors. Exposure to various hazardous substances (PCB,
      polychlorinated dibenzo-p-dioxins and dibenzo-furans [PCDD/F], metals, solvents)
      was considered. Criteria derived from human biomonitoring results of PCB were
      used for admission to the program. Participants in the surveillance program are
      first informed about risks and aims of the program. Subsequently, physicians
      started a detailed documentation of participants' general and occupational
      history, with their complaints, diseases, and nutritional habits, as well as
      information regarding their living areas, by means of a standardized
      questionnaire. In addition, separate examinations were performed to detect
      possible neurological, immunological, (neuro)psychological, hormonal, and skin
      effects. Moreover, DNA exposure as assessed by the comet assay and antioxidative
      status were determined. The program will be offered at yearly intervals for 3
      years, and then at 5 and 10 years after program onset. Until now the program has
      proved to be feasible, and acceptance among workers and their families has been
      high. Based on the results, criteria will be developed to define adverse health
      effects that might be attributable to a hazardous substance exposure.

PMID- 22994579
TI  - Nutraceuticals for blood pressure control in patients with high-normal or grade 1
      hypertension.
AB  - BACKGROUND: Current hypertension management guidelines do not recommend drug
      treatment in subjects with blood pressure (BP) in the high-normal range due to
      the risk of side effects of the currently available antihypertensive agents that
      overcomes the possible benefit. Nutraceuticals are free from relevant side
      effects and could be a valuable strategy for the treatment of these patients.
      AIM: The objective of this study was to compare the efficacy of two nutraceutical
      compositions given by the combination of policosanol, red yeast rice extract,
      berberine, folic acid and coenzyme Q(10) with or without Orthosiphon stamineus in
      lowering the BP and lipid profile. METHODS: Thirty patients with grade 1
      essential hypertension and low cardiovascular risk were analysed. At the end of a
      run-in period, patients were divided into two study arms and assigned to receive
      the nutraceutical combination with and without Orthosiphon stamineus. All
      participants underwent 24-hour ambulatory BP monitoring at the end of the run-in
      period and of the 4-week treatment with each of the two different nutraceutical
      combinations. RESULTS: In patients treated with Orthosiphon stamineus a
      significant reduction of mean 24-hour systolic and diastolic BP levels compared
      with baseline values was registered and the smoothness index calculated for
      systolic and diastolic BP showed a more reliable and homogeneous effect on BP
      over 24 hours. In contrast, nutraceutical treatment without Orthosiphon stamineus
      was not associated with a significant reduction of BP. CONCLUSIONS: Our results
      show that the addition of Orthosiphon stamineus to the combination of
      nutraceuticals confers an antihypertensive effect that allows a surprisingly
      effective 24-hour BP control in hypertensive patients.

PMID- 22994580
TI  - Comparison of exercise-induced hypertension in low birth weight and normal birth
      weight young black adults in Zimbabwe.
AB  - AIM: The objective of the study was to compare blood pressure changes during
      exercise between low and normal birth weight young Black adults. METHODS: Eighty
      medical students in their first and second year who had neonatal clinic cards as
      proof of birth weight were included in the study. Resting blood pressures and
      heart rates were recorded. Participants then underwent a multistage 9-minute
      exercise stress test while blood pressure responses were recorded at 3-minute
      intervals. The study was conducted in the Department of Physiology, University of
      Zimbabwe, College of Health Sciences, Harare, Zimbabwe. RESULTS: Of the 80
      subjects recruited, 34 had low birth weight (LBW), 26 of these were female and 8
      were male. The proportion of LBW individuals, 62% (n = 21), who developed
      exercise-induced hypertension (EIH) was significantly higher (p < 0.05) than the
      proportion of those with normal birth weight (NBW), 32% (n = 11). In addition to
      LBW being significantly associated with EIH (chi2 test p < 0.05, odds ratio 7.5)
      compared with NBW, the LBW group had a significantly higher (p < 0.05) and
      exaggerated systolic and diastolic response in stages I and II of the exercise
      protocol compared with the NBW group. CONCLUSION: LBW was associated with EIH in
      these young Black adults.

PMID- 22994581
TI  - A survey on blood pressure levels and hypertension control in a sample of the
      Italian general population.
AB  - BACKGROUND: Hypertension represents a major cardiovascular risk factor with
      relevant consequences on morbidity and mortality in the general population. An
      optimal control of blood pressure (BP) is far from being achieved. AIM: The
      objective of this study was to explore awareness of BP levels, prevalence of risk
      factors and status of hypertension control in a sample of the Italian general
      population. METHODS: Subjects aged 18 years or older were enrolled on a voluntary
      basis during the 7th and 8th World Hypertension Days at our hospital centre, S.
      Andrea Hospital in Rome, and at other hospitals throughout the Italian Lazio
      region. Along with BP measurement, a short questionnaire was completed at the
      time of the interview. RESULTS: Of 1165 individuals enrolled into the analysis,
      71.7% were aware of their BP levels (82.5% among hypertensive patients). Within
      the whole cohort, 31.9% of subjects were under antihypertensive treatment, while
      the overall rate of subjects found to be hypertensive patients at our visit was
      52.9% (n = 616). Among hypertensive patients taking antihypertensive drugs, 47.1%
      had controlled BP values with the remaining 52.9% showing uncontrolled
      hypertension. Mean systolic blood pressure (SBP) was 138.2 +/- 20.7 mmHg and mean
      diastolic blood pressure (DBP) was 80.4 +/- 11.3 mmHg in subjects receiving
      antihypertensive treatment. Among older hypertensive patients (71-94 years of
      age), only 76.9% were under treatment. Hypertensive males were more frequently
      treated than females in all age groups (p = 0.001). Smoking habit negatively
      affected efficacy of antihypertensive therapy in the age groups of 48-53 and 54
      62 years (p = 0.008 and p = 0.01, respectively). Diabetic patients had higher
      mean SBP values than non-diabetic subjects (137.3 +/- 22.1 vs 129.3 +/- 18.2
      mmHg, p = 0.02). CONCLUSION: The results of our survey strongly support the need
      for a continuing educational effort aimed at providing correct advertisement of
      healthy lifestyles and awareness of adequate BP control. Based on our
      observations, particular attention has to be paid to women, younger subjects,
      elderly subjects and diabetic patients in order to reach appropriate BP control
      and reduction of cardiovascular risk in these subject categories.

PMID- 22994582
TI  - Detection of silent myocardial ischaemia in asymptomatic diabetic patients during
      treadmill exercise testing.
AB  - BACKGROUND: Diabetic patients have an increased prevalence of atherosclerosis and
      coronary artery disease. They may also experience higher morbidity and mortality
      after acute coronary syndrome compared with non-diabetic subjects. AIM: The
      objective of this study was to determine the presence of silent myocardial
      ischaemia by treadmill test in asymptomatic diabetic patients and to compare it
      with age- and sex-matched subjects without diabetes mellitus. METHODS: The study
      design was cross-sectional and the setting was a tertiary care centre. Fifty (42
      males, 8 females) asymptomatic patients with diabetes in the age group of 30-70
      years were included in the study group and 30 (24 males, 6 females) non-diabetic
      subjects of comparable age, sex and physical activity were the control group.
      They were assessed for the presence of silent ischaemia by a standard treadmill
      test using the Bruce protocol. RESULTS: Twenty-five of 50 diabetic patients
      showed a positive response to the exercise stress test, while 7 of 30 controls
      showed stress test positivity (p < 0.05). The stress test positivity showed a
      female predilection among diabetic patients (50% in diabetic patients and 16.67%
      in controls; p < 0.05). Diabetic patients with a positive stress test showed
      higher prevalence of hypertension (36%) and dyslipidaemia (84%) compared with
      diabetic patients with a negative stress test (12% and 28%, respectively) [p <
      0.001]. The controls showed a better exercise capacity compared with diabetic
      patients; diabetic patients with a negative stress test had better exercise
      capacity than those with a positive stress test. CONCLUSIONS: The treadmill test
      is a useful, specific, cost-effective, non-invasive tool for detection of silent
      myocardial ischaemia in asymptomatic diabetic patients.

PMID- 22994584
TI  - Probable levetiracetam-related serum alkaline phosphatase elevation.
AB  - BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug with a favorable
      tolerability and safety profile with little or no effect on liver function. CASE
      PRESENTATION: Here, we reported an epileptic pediatric patient who developed a
      significant elevation in serum alkaline phosphatase level (ALP) during LEV
      monotherapy. Moreover, the serum ALP level was surprisingly decreased to normal
      after LEV discontinuation. The Naranjo Adverse Drug Reaction Probability Scale
      score was 6, indicating firstly LEV was a probable cause for the increased serum
      ALP. CONCLUSIONS: Cautious usage and concerns of the LEV-associated potential ALP
      elevation should be considered when levetiracetam is prescribed to epilepsy
      patients, especially pediatric patients.

PMID- 22994585
TI  - Inhibitory role of monovalent ions on rat brain cortex adenylyl cyclase activity.
AB  - Adenylyl cyclases, comprise of a large family of enzymes that catalyze synthesis
      of the cyclic AMP from ATP. The aim of our study was to determine the effect of
      monovalent ions on both basal, stimulated adenylate cyclase EC 4.6.1.1 (AC)
      activity and C unit of AC and on GTPase active G-protein in the synaptic
      membranes of rat brain cortex. The effect of ion concentration from 30 to 200 mM
      (1 mM MgCl2) showed dose-dependent and significant inhibition of the basal AC
      activity, stimulated and unstimulated C unit activity. Stimulation of AC with 5
      MUM GTPgammaS in the presence of 50-200 mM of tested salts showed inhibitory
      effect on the AC activity. From our results it could be postulated that the
      investigated monovalent ions exert inhibitory effect on the AC complex activity
      by affecting the intermolecular interaction of the activated alpha subunit of G/F
      protein and the C unit of AC complex an inhibitory influence of tested monovalent
      ions on these molecular interaction.

PMID- 22994586
TI  - Cardiovascular risk factors and carotid intima-media thickness are associated
      with lower cognitive performance in HIV-infected patients.
AB  - OBJECTIVES: The aim of the study was to investigate the relationship between
      metabolic comorbidities, cardiovascular risk factors or common carotid intima
      media thickness (cIMT) and cognitive performance in HIV-infected patients.
      METHODS: Asymptomatic HIV-infected subjects were consecutively enrolled during
      routine out-patient visits at two clinical centres. All patients underwent an
      extensive neuropsychological battery and assessment of metabolic comorbidities
      and cardiovascular risk factors. Moreover, cIMT was assessed by ultrasonography.
      Cognitive performance was evaluated by calculating a global cognitive impairment
      (GCI) score obtained by summing scores assigned to each test (0 if normal and 1
      if pathological). RESULTS: A total of 245 patients (median age 46 years; 84.1%
      with HIV RNA < 50 copies/mL; median CD4 count 527 cells/MUL) were enrolled in the
      study. Cardiovascular risk factors were highly prevalent in our population: the
      most frequent were dyslipidaemia (61.2%), cigarette smoking (54.3%) and
      hypertension (15.1%). cIMT was abnormal (>= 0.9mm) in 31.8% of patients. Overall,
      the median GCI score was 2 [interquartile range (IQR) 1-4]; it was higher in
      patients with diabetes (P = 0.004), hypertension (P = 0.030) or cIMT >= 0.9 mm (P
      < 0.001). In multivariate analysis, it was confirmed that diabetes (P = 0.007)
      and cIMT >= 0.9 mm (P = 0.044) had an independent association with lower
      cognitive performance. In an analysis of patients on combination antiretroviral
      therapy (cART), abacavir use was independently associated with a better cognitive
      performance (P = 0.011), while no association was observed for other drugs or
      neuroeffectiveness score. CONCLUSIONS: Diabetes, cardiovascular risk factors and
      cIMT showed a strong association with lower cognitive performance, suggesting
      that metabolic comorbidities could play a relevant role in the pathogenesis of
      HIV-associated neurocognitive disorders in the recent cART era.

PMID- 22994587
TI  - Children trust a consensus composed of outgroup members--but do not retain that
      trust.
AB  - Children prefer to learn from informants in consensus with one another. However,
      no research has examined whether this preference exists across cultures, and
      whether the race of the informants impacts that preference. In 2 studies, one
      hundred thirty-six 4- to 7-year-old European American and Taiwanese children
      demonstrated a systematic preference for a consensus. Nevertheless, the initial
      strength and persistence of that preference depended on the racial composition of
      the consensus. Children's preference for consensus members belonging to the same
      race as themselves persisted even when only one consensus member remained to
      provide information. When the consensus consisted of different-race informants,
      preference for the consensus was initially apparent but lost when only one member
      from the consensus remained with the dissenting informant.

PMID- 22994588
TI  - Localization of a subset of yeast mRNAs depends on inheritance of endoplasmic
      reticulum.
AB  - Localization of messenger RNA (mRNAs) contributes to generation and maintenance
      of cellular asymmetry, embryonic development and neuronal function. The She1-3
      protein machinery in Saccharomyces cerevisiae localizes >30 mRNAs to the bud tip,
      including 13 mRNAs encoding membrane or secreted proteins. Ribonucleoprotein
      (RNP) particles can co-localize with tubular endoplasmic reticulum (ER)
      structures that form the initial elements for segregation of cortical ER (cER),
      suggesting a coordination of mRNA localization and cER distribution. By
      investigating localization of MS2-tagged mRNAs in yeast defective at various
      stages of cER segregation, we demonstrate that proper cER segregation is required
      for localization of only a subset of mRNAs. These mRNAs include WSC2, IST2, EAR1
      and SRL1 that encode membrane or ER associated proteins and are expressed during
      S and G2 phases of the cell cycle when tubular ER movement into the bud occurs.
      Translation of WSC2 is not required for localization, ruling out co-translational
      targeting of this mRNA. Localization of ASH1 mRNA is independent of cER
      segregation, which is consistent with the expression pattern of ASH1 at late
      mitosis. Our findings indicate the presence of two different pathways to localize
      mRNAs to the yeast bud.

PMID- 22994589
TI  - Enrichment of regulatory T cells in acutely rejected human liver allografts.
AB  - Acute cellular rejection (ACR) occurs frequently after liver transplantation and
      can usually be controlled. Triggering of allospecific immune responses and lack
      of immunoregulation are currently suggested as a cause of ACR, but there are no
      investigations of intrahepatic immune responses during ACR. Therefore we
      prospectively analyzed the intrahepatic T cell infiltration pattern in
      correlation to the severity of ACR in a cohort of patients with graft hepatitis
      (n = 151). While CD4(+)  cells dominated the portal infiltrates in mild-moderate
      ACR, CD8(+)  cells prevailed in severe ACR. Furthermore portal CD8(+)  and not
      CD4(+)  infiltration correlated with serum transaminases and with the likelihood
      of subsequent ACRs. Surprisingly, the rise of portal effector T cells density
      during ACR was surpassed by the increase in portal infiltration of regulatory T
      cells by a factor of two. Thus ACRs rather showed an increase and not a lack of
      regulation, as was suggested by analysis of peripheral blood mononuclear cells.
      Despite the pattern of enhanced immunoregulation, patients with severe ACR had a
      higher risk for subsequent rejections and showed a trend to a reduced survival.
      Thus, patients with severe rejections might need a modification of their
      immunosuppression to improve prognosis.

PMID- 22994590
TI  - The social location of heavy episodic alcohol consumption in the Victorian
      population.
AB  - INTRODUCTION AND AIMS: To examine heavy episodic drinking across demographic
      subgroups to identify where heavy episodic drinking is socially located in an
      Australian state. DESIGN AND METHODS: Cross-sectional survey, 2483 adult
      Victorians using Computer Assisted Telephone Interviewing. Two measures of heavy
      drinking were used: (i) heavy episodic drinking-more than five standard drinks at
      least weekly; and (ii) typically heavy drinking-50% or more of all drinking
      occasions involving consumption of 5+ standard drinks. Associations between heavy
      episodic drinking and eight potential sociodemographic correlates (gender, age,
      education, income, marital status, ethnic origin, religion and geographical
      remoteness) were examined. RESULTS: There were few significant correlates of
      heavy episodic drinking apart from gender and age, once gender and age were
      controlled. Men were more likely to report heavy episodic drinking than women,
      but this was attenuated in the measure of typically heavy drinking, suggesting
      that women reporting heavy episodic drinking were more likely to typically drink
      that much when they drank. Younger people were more likely to report weekly heavy
      episodic drinking and more likely to report engaging in this pattern on at least
      half of their drinking occasions, and this was also true for those unmarried or
      in de facto relationships. Those of Asian background were less likely to report
      heavy drinking. In multivariate analysis, the remaining sociodemographic
      variables were largely unrelated to the drinking measures. DISCUSSION AND
      CONCLUSION: The study clearly shows that the prevalence of heavy episodic
      drinking varies particularly across gender and age groups in Victoria. These
      variations appear to hold across key sociodemographic variables such as income
      and education.

PMID- 22994591
TI  - Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on
      the outcome in patients with severe sepsis or septic shock.
AB  - Sepsis and its sequelae of multiple organ failure is one of the leading causes of
      death in the industrial countries. Several studies have shown that patients who
      are treated with low-dose acetyl salicylic acid (ASA) for secondary prevention of
      atherothrombosis may have a lower risk to develop organ failure in the case of
      critical illness. The benefit of ASA is probably due to an inhibition of platelet
      activation as well as an increase in the formation of anti-inflammatory lipoxin
      A4. On the other hand, the effect of ASA could be - at least partially - an
      indirect one, caused by atherosclerotic vascular diseases as the cause of ASA
      treatment. Atherosclerosis is considered as a moderate systemic inflammation and
      we hypothesise that this chronic condition could have an impact on the outcome in
      sepsis. To get more information on the benefit of ASA in critically ill patients
      and on possible interference with atherosclerotic vascular diseases, we analysed
      the medical records of 886 septic patients who were admitted to the surgical
      intensive care unit (ICU) of a university hospital. Logistic regression analysis
      indicated that patients who were treated during the ICU stay with ASA (100 mg/d)
      had a significantly lower mortality. Odds ratios (ORs; with 95% confidential
      intervals) of 0.56 (0.37-0.84) and 0.57 (0.39-0.83) were calculated for ICU and
      hospital mortality, respectively. In contrast, statin treatment did not have
      significant effect on mortality. Diagnosis of atherosclerotic vascular diseases
      according to ICD classification did not influence ICU mortality but lowered
      hospital mortality (OR = 0.71 (0.52-0.99)). Subgroup analysis provided
      preliminary evidence that clopidogrel when given as only anti-platelet drug may
      have a similar benefit as ASA, but the combination of ASA and clopidogrel failed
      to improve the outcome. The time course of plasma fibrinogen and procalcitonin
      levels indicate that ASA seems to reduce the activation of haemostasis and
      increase the resolution of inflammation. It is concluded that prospective
      interventional studies should be done to test the use of ASA as novel therapeutic
      approach in critically ill patients. 

PMID- 22994592
TI  - Dietary tools to modulate glycogen storage in gilthead seabream muscle: glycerol
      supplementation.
AB  - The quality and shelf life of fish meat products depend on the skeletal muscle's
      energetic state at slaughter, as meat decomposition processes can be exacerbated
      by energy depletion. In this study, we tested dietary glycerol as a way of
      replenishing muscle glycogen reserves of farmed gilthead seabream. Two diets were
      tested in duplicate (n = 42/tank). Results show 5% inclusion of crude glycerol in
      gilthead seabream diets induces increased muscle glycogen, ATP levels and
      firmness, with no deleterious effects in terms of growth, proximate composition,
      fatty acid profile, oxidative state, and organoleptic properties (aroma and
      color). Proteomic analysis showed a low impact of glycerol-supplementation on
      muscle metabolism, with most changes probably reflecting increased stress coping
      capacity in glycerol-fed fish. This suggests inclusion of crude glycerol in
      gilthead seabream diets (particularly in the finishing phase) seems like a viable
      strategy to increase glycogen deposition in muscle without negatively impacting
      fish welfare and quality.

PMID- 22994594
TI  - Unravelling mitochondrial retrograde regulation in the abiotic stress induction
      of rice ALTERNATIVE OXIDASE 1 genes.
AB  - Mitochondrial retrograde regulation (MRR) is the transduction of mitochondrial
      signals to mediate nuclear gene expression. It is not clear whether MRR is a
      common regulation mechanism in plant abiotic stress response. In this study, we
      analysed the early abiotic stress response of the rice OsAOX1 genes, and the
      induction of OsAOX1a and OsAOX1b (OsAOX1a/b) was selected as a working model for
      the stress-induced MRR studies. We found that the induction mediated by the
      superoxide ion (O2.(-) )-generating chemical methyl viologen was stronger than
      that of hydrogen peroxide (H2 O2 ). The addition of reactive oxygen species (ROS)
      scavengers demonstrated that the stress induction was reduced by eliminating O2.(
      ) . Furthermore, the stress induction did not rely on chloroplast- or cytosol
      derived O2.(-) . Next, we generated transgenic plants overexpressing the
      superoxide dismutase (SOD) gene at different subcellular locations. The results
      suggest that only the mitochondrial SOD, OsMSD, attenuated the stress induction
      of OsAOX1a/b specifically. Therefore, our findings demonstrate that abiotic
      stress initiates the MRR on OsAOX1a/b and that mitochondrial O2.(-) is involved
      in the process.

PMID- 22994595
TI  - The substance view: a critique (part 2).
AB  - In my initial critique of the substance view, I raised reductio-style objections
      to the substance view's conclusion that the standard human fetus has the same
      intrinsic value and moral standing as the standard adult human being, among
      others. In this follow-up critique, I raise objections to some of the premises
      invoked in support of this conclusion. I begin by briefly presenting the
      substance view as well as its defense. (For a more thorough presentation, see the
      first part of my critique.) I then raise objections to three claims involved in
      the substance view's defense: the claim that the standard human fetus's intrinsic
      value and moral standing is a function of its potentiality; the claim that the
      standard human fetus's intrinsic value and moral standing is a function of its
      essential properties; and the claim that it is the possession of the basic
      potential for rational moral agency that best accounts for the wrongness of
      killing the standard human fetus, among others. 

PMID- 22994596
TI  - Enhanced protocol for CD14+ cell enrichment from equine peripheral blood via anti
      human CD14 mAb and automated magnetic activated cell sorting.
AB  - REASONS FOR PERFORMING STUDY: CD14 positive (CD14+) cells are the precursor cells
      of monocyte-derived dendritic cells (DCs). In horses their potent antigen
      presenting capacity and ability to induce an effective immune response classify
      these cells suitable for several therapeutic approaches such as for equine
      sarcoid. However, in horses, the generation efficiency of DCs from adherent
      peripheral blood mononuclear cells (PBMCs) is currently still poor. OBJECTIVES:
      Establishment of a simple short protocol to enhance DC generation in horses by
      using a human CD14 monoclonal antibody (mAb) and an automated magnetic activated
      cell sorting (MACS) system. METHODS: Peripheral blood mononuclear cells were
      isolated from fresh heparinised blood samples of 3 horses and primarily stained
      for flow cytometric analysis (FACS) with a mAb against human CD14 as well as a
      secondary phycoerythrin (PE) conjugated antibody to determine the initial
      percentage of CD14 cells in the sample. Peripheral blood mononuclear cells were
      used for automated MACS using the same primary and secondary antibodies and
      analysed by FACS. CD14+ selected cells were cultured for 4 days adding
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL
      4) to the culture media. Dendritic cell generation was assessed analysing cell
      morphology and surface marker expression (hCD83, hCD86, eqMHCII). RESULTS: Prior
      to selection, the mean percentage of CD14+ cells in the total cell population was
      5.5%, further gaiting of this cell population resulted in 78.46% CD14+ monocytes.
      After our positive selection the mean percentage of CD14+ cells in the population
      was 98% without affecting viability. After culture, DC yield was 2-fold higher
      than in previous published outcomes. CONCLUSIONS: The additional CD14 cell
      separation step after PBMC isolation significantly amplified the number of CD14+
      cells, increasing the number of generated DCs. POTENTIAL RELEVANCE: The number of
      DCs available is critical for further use of these cells and the herein described
      protocol will therefore help to improved DC generation for therapeutic approaches
      in horses.

PMID- 22994597
TI  - Involvement of the aorta in brucellosis: the forgotten, life-threatening
      complication. A systematic review.
AB  - Human brucellosis is a disease of protean manifestations, and has been implicated
      in complications and focal disease in many human organ systems. However, little
      is collectively known about the background, the course, the clinical
      characteristics, the diagnostic issues raised, and the short- and long-term
      therapeutic approaches in patients with aortic involvement as a complication of
      brucellosis. With the aim to glean from the literature useful information to
      better understand and manage this complication, a computerized search without
      language restriction was conducted using PubMed and SCOPUS. An article was
      considered eligible for inclusion in the systematic review if it reported data on
      patients with involvement of the aorta due to a Brucella infection. The
      epidemiologic and clinical characteristics of 44 cases of brucellar aortic
      involvement found through the systematic review of the literature were analyzed
      together with those of two new cases that we treated in the recent past. This
      complication involved the ascending thoracic aorta in 18 cases (in 16 of them as
      a consequence of brucellar endocarditis), and the descending thoracic aorta or
      the abdominal aorta in the remaining 30 cases. In the latter it was associated
      with spondylodiscitis of the lumbar spine in 13 cases. History of or symptoms
      indicative of brucellosis were not universally present. Brucellar aortic
      involvement represents a possibly underdiagnosed and underreported complication
      with major morbidity and mortality potential. Experience with novel invasive
      therapeutic approaches remains limited. Early suspicion through detailed history
      and diagnosis, aided by advances in aortic imaging, would allow for better
      planning of therapeutic interventions.

PMID- 22994599
TI  - The cost of copy number in a selfish genetic element: the 2-MUm plasmid of
      Saccharomyces cerevisiae.
AB  - Many autonomously replicating genetic elements exist as multiple copies within
      the cell. The copy number of these elements is often assumed to have important
      fitness consequences for both element and host, yet the forces shaping its
      evolution are not well understood. The 2 MUm is a multicopy plasmid of
      Saccharomyces yeasts, encoding just four genes that are solely involved in
      plasmid replication. One simple model for the fitness relationship between yeasts
      and 2 MUm is that plasmid copy number evolves as a trade-off between selection
      for increased vertical transmission, favouring high copy number, and selection
      for decreased virulence, favouring low copy number. To test this model, we
      experimentally manipulated the copy number of the plasmid and directly measured
      the fitness cost, in terms of growth rate reduction, associated with high plasmid
      copy number. We find that the fitness burden imposed by the 2 MUm increases with
      plasmid copy number, such that each copy imposes a fitness burden of 0.17% (+/-
      0.008%), greatly exceeding the cost expected for it to be stably maintained in
      yeast populations. Our results demonstrate the crucial importance of copy number
      in the evolution of yeast per 2 MUm associations and pave the way for future
      studies examining how selection can shape the cost of multicopy elements.

PMID- 22994598
TI  - The burden of moderate to severe psoriasis: an overview.
AB  - Psoriasis is a chronic, immune-mediated skin disorder that affects 1-3% of the
      general population worldwide. While considered a non-life-threatening disease,
      psoriasis represents a social and financial burden for patients and the
      healthcare system. Individuals suffer from disfigurement and from social
      stigmatization. Because the disease is usually persistent, patients with a
      diagnosis of psoriasis usually need lifelong care, which also means a lifetime of
      expenses. We aimed to conduct a comprehensive review of the evidence available
      concerning the social burden and costs of psoriasis. A search for the keywords
      'quality of life' (QOL) or 'burden' or 'stigmatization' or 'psychological
      factors' in PubMed up to January 2010 yielded a total of 817 studies. QOL was
      affected by psoriasis to a degree comparable with diabetes or cancer. A search
      for 'cost-of-illness analyses', in the same period, yielded only seven papers
      satisfying entry criteria. All the studies but one were performed before
      biologics became available for psoriasis treatment. Direct costs were higher than
      indirect costs, with hospitalization representing the most significant item.
      Treatment costs showed wide variations between different studies. Reasons for
      these discrepancies are manifold including differences in the selection of the
      sample, as well as in the methods for calculating costs. There is a need to
      harmonize methodologies. For a final conclusive judgement of the cost
      effectiveness of innovative therapies such as biological agents, long-term
      economic consequences have to be evaluated and long-term remission rates and
      complications considered.

PMID- 22994600
TI  - Encouraging early preventive dental visits for preschool-aged children enrolled
      in Medicaid: using the extended parallel process model to conduct formative
      research.
AB  - OBJECTIVE: Preventive dental visits for preschool-aged children can result in
      better oral health outcomes, especially for children from lower income families.
      Many children, however, still do not see a dentist for preventive visits. This
      qualitative study examined the potential for the Extended Parallel Process Model
      (EPPM) to be used to uncover potential antecedents to parents' decisions about
      seeking preventive dental care. METHODS: Seventeen focus groups including 41
      parents were conducted. The focus group protocol centered on constructs
      (perceived severity, perceived susceptibility, perceived self-efficacy, and
      perceived response efficacy) of the EPPM. Transcripts were analyzed by three
      coders who employed closed coding strategies. RESULTS: Parents' perceptions of
      severity of dental issues were high, particularly regarding negative health and
      appearance outcomes. Parents perceived susceptibility of their children to dental
      problems as low, primarily because most children in this study received
      preventive care, which parents viewed as highly efficacious. Parents' self
      efficacy to obtain preventive care for their children was high. However, they
      were concerned about barriers including lack of dentists, especially dentists who
      are good with young children. CONCLUSIONS: Findings were consistent with EPPM,
      which suggests this model is a potential tool for understanding parents'
      decisions about seeking preventive dental care for their young children. Future
      research should utilize quantitative methods to test this model.

PMID- 22994601
TI  - Dialysate quality: new standards require a new approach to compliance.
AB  - Substances commonly found in drinking water can injure hemodialysis patients if
      they are not removed from the water during the preparation of dialysate.
      Standards have been developed that specify the maximum allowable levels of these
      substances in dialysate. Those standards have recently been revised. While the
      maximum allowable levels of chemical contaminants have not changed, a more
      sensitive method for bacterial cultures has been specified and the maximum
      allowable levels of bacteria and endotoxin in the new standards have been
      decreased. These decreases are a consequence of an increasing body of evidence
      that improving dialysate quality positively impacts patient outcomes. Meeting the
      new microbiological standards could require dialysis facilities to adopt new
      approaches to managing their water treatment and concentrate preparation systems.
      To address this need, the new standards present a framework for developing a
      facility-specific quality management system for ensuring dialysate quality based
      on validation of system performance, coupled with routine monitoring and periodic
      revalidation of performance.

PMID- 22994602
TI  - Hemodialysis adequacy and the hospitalized end-stage renal disease patient-
      raising awareness.
AB  - Assessment of hemodialysis adequacy may require different approaches for the
      stable, outpatient with end-stage renal disease (ESRD) and for the sick,
      inpatient with acute kidney injury (AKI). Variability of urea distribution
      volume, urea generation, and treatment schedule, for instance, complicates
      dialysis dosing in the latter group although progress has been made in our
      understanding of their needs. There is a third population, however, for whom
      hemodialysis dosing requirements remain unclear--the hospitalized ESRD patient.
      This commentary discusses the key urea kinetic differences between stable ESRD
      and AKI to give the context to where, on the intervening spectrum, the
      hospitalized ESRD patient might lie. The limited literature examining
      hemodialysis dosing in this population is discussed along with those outstanding
      questions that might form the basis of a future research agenda.

PMID- 22994605
TI  - Collaborative modelling: the future of computational neuroscience?
AB  - Given the complexity of biological neural circuits and of their component cells
      and synapses, building and simulating robust, well-validated, detailed models
      increasingly surpasses the resources of an individual researcher or small
      research group. In this article, I will briefly review possible solutions to this
      problem, argue for open, collaborative modelling as the optimal solution for
      advancing neuroscience knowledge, and identify potential bottlenecks and possible
      solutions.

PMID- 22994606
TI  - Species-specific time trends and enantiomer fractions of hexabromocyclododecane
      (HBCD) in biota from East Greenland.
AB  - Time trends of hexabromocyclododecane (HBCD) isomers were studied for glaucous
      gull and ringed seal from East Greenland. The ringed seal results extended a
      previous time trend (1986-2008) to 2010. alpha-HBCD was the only isomer
      consistently above quantification limits. For glaucous gull liver, annual median
      values of alpha-HBCD (1994-2010) ranged from 22 to 120 ng/g lipid weight (lw)
      with no significant trend, while HBCD in ringed seal blubber from the same area
      showed a significant increase from 3.9 to 11 ng/g lw (1986-2010). Reasons for
      this difference are unknown, but might include different feeding habits and
      species-specific metabolisation processes. Concentrations of several
      organochlorine (OC) compounds were determined for glaucous gull and ringed seal
      samples collected from the same area in 2004. HBCD concentrations in glaucous
      gull liver appeared relatively low when compared to OC concentrations in the same
      tissue and to both HBCD and OCs in ringed seal blubber from the same area.
      Enantiomer fractions (EF) deviated significantly from racemic for all annual mean
      EFs in glaucous gull suggesting metabolisation processes toward an enrichment of
      (-)alpha-HBCD. For ringed seal, this enrichment was less pronounced and only
      significant for two of the ten years. For neither species, significant changes in
      EF were found over time.

PMID- 22994607
TI  - Management of rifamycins-everolimus drug-drug interactions in a liver-transplant
      patient with pulmonary tuberculosis.

PMID- 22994608
TI  - Synthesis and characterization of phenolic Mannich bases and effects of these
      compounds on human carbonic anhydrase isozymes I and II.
AB  - Mannich bases 2a-f derived from 3,4-dimethylphenol (1), formaldehyde and
      different amines are prepared and subjected to spectral (IR, (1)H and (13)C NMR)
      and elemental analyses. The inhibition of two human carbonic anhydrase (hCA, EC
      4.2.1.1) isozymes I and II, with 1 and synthesized Mannich bases 2a-f and
      acetazolamide (AAZ) as a control compound was investigated in vitro by using the
      hydratase and esterase assays. In relation to hydratase and esterase activities
      of the half maximal inhibitory concentration (IC(50)) and the inhibition
      equilibrium constants (K(i))values were determined. Only two compounds (2a and
      2e)exhibit weak hCA II inhibitory effects on esterase activity. IC(50) and Ki
      values for 2a and 2e with respect to esterase activity of hCA II are0.88 * 10(3)
      and 6.3-7.6 uM and 0.44 * 10(3) and 19.0-96.4 uM,respectively. On the contrary,
      compounds 2b and 2d might be used as CA activators due to increasing esterase
      activity of hCA I and hCA II isozymes.

PMID- 22994609
TI  - Successful transplantation of reduced-sized rat alcoholic fatty livers made
      possible by mobilization of host stem cells.
AB  - Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for
      transplantation. Reduced sized (50%) livers or whole livers were transplanted
      into normal DA recipients, which, in this strain combination, survive
      indefinitely when the donor has not been fed alcohol. However, none of the rats
      survived a whole fatty liver transplant while six of seven recipients of reduced
      sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly
      increased in reduced size liver grafts compared to whole liver grafts. Lineage
      negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the
      peripheral blood and in allografts after reduced size fatty liver
      transplantation. In contrast, there were meager increases in cells reactive with
      anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic
      liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5
      of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with
      neutralizing antibodies diminished stem cell recruitment and four of five reduced
      sized fatty liver recipients died. Thus chemokine insufficiency was associated
      with transplant failure of whole grafts, which was overcome by the increased
      regenerative requirements promoted by the small grafts and mediated by SDF-1
      resulting in stem cell influx.

PMID- 22994610
TI  - End-stage renal disease and dialysis in HIV-positive patients: observations from
      a long-term cohort study with a follow-up of 22 years.
AB  - OBJECTIVES: Renal disease is a common and serious complication in HIV-infected
      patients. METHODS: A retrospective cohort analysis for the period 1989-2010 was
      carried out to determine the prevalence, incidence and risk factors for end-stage
      renal disease (ESRD). ESRD was defined as initiation of renal replacement
      therapy. Three time periods were defined: 1989-1996 [pre-highly active
      antiretroviral therapy (HAART)], 1997-2003 (early HAART) and 2004-2010 (late
      HAART). RESULTS: Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative
      observation time 68 084 patient-years (PY)] were analysed. ESRD was newly
      diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity
      [relative risk (RR) 5.1; 95% confidence interval (CI) 2.3-10.3; P < 0.0001],
      injecting drug use (IDU) (RR 2.3; 95% CI 1.1-4.6; P = 0.02) and hepatitis C virus
      (HCV) coinfection (RR 2.2; 95% CI 1.1-4.2; P = 0.03). The incidence of ESRD
      decreased in Black patients over the three time periods [from 788.8 to 130.5 and
      164.1 per 100 000 PY of follow-up (PYFU), respectively], but increased in
      Caucasian patients (from 29.9 to 41.0 and 43.4 per 100 000 PYFU, respectively).
      The prevalence of ESRD increased over time and reached 1.9 per 1000 patients in
      2010. Mortality for patients with ESRD decreased nonsignificantly from period 1
      to 2 (RR 0.72; P = 0.52), but significantly from period 1 to 3 (RR 0.24; P =
      0.006), whereas for patients without ESRD mortality decreased significantly for
      all comparisons. ESRD was associated with a high overall mortality (RR 9.9; 95%
      CI 6.3-14.5; P < 0.0001). CONCLUSION: As a result of longer survival, the
      prevalence of ESRD is increasing but remains associated with a high mortality.
      The incidence of ESRD declined in Black but not in Caucasian patients. IDU and
      HCV were identified as additional risk factors for the development of ESRD.

PMID- 22994611
TI  - Developing effective animal-assisted intervention programs involving visiting
      dogs for institutionalized geriatric patients: a pilot study.
AB  - AIM: An ever increasing interest in the therapeutic aspects of the human-animal
      bond has led to a proliferation of animal-assisted interventions (AAI) involving
      dogs. However, most of these programs lack a solid methodological structure, and
      basic evaluative research is needed. The purpose of this study was to test the
      value of dog-assisted interventions as an innovative tool to increase quality of
      life in the geriatric population. METHODS: Nineteen patients (men and women) with
      a mean age of 85 years participated in the study. Interactions between patients
      and visiting dogs occurred either in a social situation (socialization sessions)
      or in a therapeutic context (physical therapy sessions). We derived and
      characterized a specific ethogram of elderly-dog interactions aimed at evaluating
      the effectiveness of visiting dogs in improving mood, catalyzing social
      interactions and reducing their everyday apathetic state. Cortisol levels were
      also measured in the saliva, and depressive state was evaluated. RESULTS:
      Overall, results show a time-dependent increase in social behaviour and
      spontaneous interactions with the dogs. Dog-mediated interactions affected the
      daily increase in cortisol levels, thus having an 'activational effect', in
      contrast to the apathetic state of institutionalized elderly. CONCLUSIONS: Dog
      mediated intervention programs appear to be promising tools to improve the social
      skills and enrich the daily activities of the institutionalized elderly.

PMID- 22994612
TI  - Altered risk-aversion and risk-taking behaviour in patients with Alzheimer's
      disease.
AB  - AIM: Normal individuals are risk averse for decisions framed as gains but risk
      taking for decisions framed as losses. This framing effect is supposed to be
      attenuated in Alzheimer's disease (AD) patients. We investigated the effects of
      highlighting rewards versus highlighting punishments on the risky decision-making
      of AD patients. METHOD: Fourteen mild to moderate AD patients (Mini-Mental Status
      Examination score, 11-23; Clinical Dementia Rating, 1-2) and 16 healthy
      volunteers were recruited for the study. Subjects completed a computerized task
      on risky decision-making in which mathematically equivalent dilemmas were
      presented in terms of opportunities to gain monetary rewards ('positive frame')
      or avoid suffering losses ('negative frame'). RESULTS: As expected, AD patients
      chose more risky options under the positive frame than the negative frame,
      contrary to the control group (Z =-2.671, P= 0.007). The normal difference in the
      distribution of risky choices between positively and negatively framed dilemmas
      was significantly reduced in the AD group after we adjusted for years of
      education, mean age and depression (F= 5.321, P= 0.030). Deliberation time did
      not differ significantly between the two groups. CONCLUSION: These results
      suggest that AD patients making high-risk choices is associated with attenuated
      sensitivity to the emotional frames that highlight rewards or punishments,
      possibly reflecting altered evaluations of prospective gains and losses.

PMID- 22994613
TI  - A comparison of family care infrastructure for demented elderly in inner cities
      and regional areas in Japan.
AB  - BACKGROUND: Family members' observations of daily life are important for the
      diagnosis and treatment of dementia. However, elderly people are increasingly
      living alone, and family structures tend to differ between inner-city areas and
      regional areas. We aimed to compare the family caregiving infrastructure of
      demented elderly visiting a memory clinic. METHODS: Subjects were consecutive
      outpatients with dementia at the memory clinic at a university hospital in two
      different areas. We compared subjects' demographic data, residency status,
      housemates and companion status at the time of their initial visit. RESULTS:
      Patients in the inner-city area (n= 99) had more education and higher Mini-Mental
      State Examination scores than those in the regional area (n= 172). In both areas,
      the highest proportion of patients lived with their spouse. In the inner city,
      patients' housemates were either their spouse (34%) or their child (13%); 22%
      lived alone. In regional areas, patients lived with their spouse only (39%) or in
      their child's household (23%); 14% lived alone. At their initial consultation,
      inner-city patients were accompanied by a family member other than their spouse
      (49%), a spouse (27%), or they were alone (7%). In the regional area, patients'
      companions were their spouse (35%) or their spouse and other family members
      (18%); patients rarely arrived alone. Regression analysis showed that education,
      diagnosis, housemate state (child only), and companion state (alone)
      significantly influenced the living area. CONCLUSION: Our results suggest family
      caregiving infrastructure of demented elderly differ between the two areas. This
      may reflect changes in social structure and increased awareness regarding
      dementia in inner-city areas.

PMID- 22994614
TI  - Safety and tolerability of rivastigmine transdermal patch formulation in newly
      diagnosed patients with Alzheimer's dementia in naturalistic conditions.
AB  - AIM: The majority of available data on safety and tolerability issues regarding
      cholinesterase inhibitors used for the treatment of Alzheimer's disease has been
      available for orally administered formulations. The objective of this
      prospective, 24 week, observational, non-interventional post-marketing
      surveillance study was to evaluate the safety and tolerability, as well as the
      efficacy, of the rivastigmine transdermal patch formulation in newly diagnosed
      patients with Alzheimer's dementia in naturalistic conditions. METHODS: Safety
      and tolerability assessment included the monitoring and recording of adverse
      events and withdrawals at any time during the study. The efficacy parameter was
      determined based on the score of the Mini-Mental State Examination. RESULTS: Out
      of the 433 patients, 11 patients (2.54%) suffered serious adverse events. Non
      serious adverse events were reported in 179 patients (41.34%). As adverse event
      is defined as any untoward medical occurrence that may present during treatment
      with a pharmaceutical product but that does not necessarily have a causal
      relationship with this treatment. The most common adverse event in the present
      study was a decline in the Mini-Mental State Examination score in 97 patients
      (22.40%). The second most common non-serious adverse event was a skin reaction in
      61 patients (14.09%). Treatment with rivastigmine continued in 139 cases (32.10%)
      and was discontinued in 40 cases (9.24%). The median Mini-Mental State
      Examination score observed at the time of inclusion was 21.0, and after 6 months,
      it was 22.0 (W 63441; P < 0.001). Because of several limitations, the open-label
      design of the present study necessitates caution when interpreting the results.
      CONCLUSIONS: The results of this study suggest that the rivastigmine transdermal
      patch is safe and tolerable for Alzheimer's dementia patients in naturalistic
      conditions.

PMID- 22994615
TI  - Efficacy of a high dosage of donepezil for Alzheimer's disease as examined by
      single-photon emission computed tomography imaging.
AB  - BACKGROUND: The efficacy of donepezil 10 mg/day against Alzheimer's disease (AD)
      was examined, with a primary focus on changes in cerebral blood flow (CBF) as
      determined by single-photon emission computed tomography imaging. METHODS: The
      subjects were 24 outpatients who had been diagnosed with probable AD, which had
      progressed to advanced AD. Mini-Mental State Examination and Alzheimer's Disease
      Assessment Scale (ADAS) scores were determined before and after the donepezil
      dosage increase. (99m) Tc-ethylcysteinate dimer single-photon emission computed
      tomography was performed to evaluate changes in CBF. Then, a comparative study
      evaluated changes after the donepezil dosage increased. RESULTS: After the
      donepezil dosage increase, adverse effects associated with gastrointestinal
      symptoms were observed in one patient, and irritability was observed in three.
      The average Mini-Mental State Examination score changed from 15.25 +/- 6.24 to
      14.67 +/- 6.07; significant changes were not observed. Seventeen subjects were
      evaluated with the Alzheimer's Disease Assessment Scale-cognitive subscale. After
      the dosage increase, the average subscale score decreased from 24.52 +/- 13.39 to
      21.56 +/- 9.14, and significant improvement was observed (P = 0.021). With
      respect to changes in the CBF, the values of all three indicators decreased after
      the higher dosage increased CBF. However, no significant differences were
      observed in CBF. Analysis performed after the donepezil dosage increase revealed
      significant increases in CBF in the right occipital and temporal lobes, left
      temporal lobe, right parietal lobe, and both parts of the posterior cerebellum.
      CONCLUSION: Increasing the donepezil dosage from 5 mg/day to 10 mg/day is
      effective for the treatment of AD.

PMID- 22994616
TI  - Living alone is associated with depression among the elderly in a rural community
      in Japan.
AB  - AIM: This study aimed to investigate factors associated with depression in a
      sample of elderly Japanese individuals in a rural community and to examine
      differences among factors associated with individuals living alone or living with
      others. METHODS: Using a population-based sample from rural Japan, we assessed a
      total of 1552 participants aged 65 years or older by mailing a survey and
      evaluating responses based on the Geriatric Depression Scale. Factors associated
      with depression were also examined. RESULTS: We received 964 valid responses.
      Depressed subjects comprised 20.5% of the sample. Living alone was significantly
      related to depression. In individuals living alone, depression was associated
      with loss of appetite, suicidal ideation, financial strain, and worries in life.
      However, multiple linear regression analyses revealed that the influence of
      living alone was negated by having a good social support system. CONCLUSION:
      These findings confirm that living alone is an important factor in depression
      among the elderly in a rural part of Japan. Results also confirm what others have
      found in Western cultures: high levels of social support, awareness of receiving
      social support, and willingness to receive assistance may reduce the risk of
      depression.

PMID- 22994617
TI  - Functional dependence and caregiver burden in Alzheimer's disease: a controlled
      trial on the benefits of motor intervention.
AB  - BACKGROUND: Cognitive decline has a negative impact on functional activities in
      Alzheimer's disease. Investigating the effects of motor intervention with the
      intent to reduce the decline in functionality is an expected target for patients
      and caregivers. The aim of this study was to verify if a 6-month motor
      intervention programme promoted functionality in Alzheimer's patients and
      attenuated caregivers' burden. METHODS: The sample comprised 32 community
      patients with Alzheimer's disease and their 32 respective caregivers. Patients
      were divided into two groups: 16 participated in the motor intervention programme
      and 16 controls. Subjects performed 60 minutes of exercises, three times per week
      during the 6-month period, to improve flexibility, strength, agility and balance.
      Caregivers followed the procedures with their patients during this period.
      Functionality was evaluated by the Berg Functional Balance Scale and the
      Functional Independence Measure. Caregivers completed the Neuropsychiatric
      Inventory Caregiver Distress Scale and the Zarit Carer Burden Scale. Two-way
      ANOVA was used to verify the interaction between time (pre- and post
      intervention) and the motor intervention program. RESULTS: While patients in the
      motor programme preserved their functionality, as assessed by the Functional
      Independence Measure, the controls suffered a relative decline (motor
      intervention group: from 109.6 to 108.4 vs controls: from 99.5 to 71.6; P= 0.01).
      Patients from motor intervention also had better scores than the controls on
      functional balance assessed by Berg scale (F: 22.2; P= 0.001). As assessed by the
      Neuropsychiatric Inventory and Zarit scale, burden was reduced among caregivers
      whose patients participated in the motor intervention programme compared with
      caregivers whose patients did not participate in this programme (Neuropsychiatric
      Inventory, caregiver's part: F: 9.37; P= 0.01; Zarit: F: 11.28; P= 0.01).
      CONCLUSION: Patients from the motor intervention group showed reduced functional
      decline compared to the controls, and there was an associated decrease in
      caregivers' burden.

PMID- 22994618
TI  - Randomized controlled trial of home rehabilitation for patients with ischemic
      stroke: impact upon disability and elderly depression.
AB  - BACKGROUND: Patients with major stroke are often left with disability and may
      have depression and dementia during the recovery phase. Rehabilitation programmes
      have been shown to improve short-term physical outcome, but their long-term
      effectiveness and impact on dementia and depression are uncertain. METHODS: We
      performed a 6-month randomized controlled trial of a home rehabilitation
      programme and compared it with the standard care patients with recent ischemic
      stroke receive. The intervention group received home-based physical therapy once
      a month for 6 months, along with educational support, counselling and audiovisual
      materials. The control group received rehabilitation as prescribed by a physician
      and educational materials upon discharge from hospital. The primary measurement
      was a change in Barthel Index. Secondary measurements were the Hospital Anxiety
      and Depression Scale (HADS) and Thai Mini-Mental State Examination. RESULTS: Of
      the 68 screened patients, 60 patients were enrolled. At baseline, there was no
      significant difference in patient characteristics between the two groups. Over 2
      years, the mean Barthel Index and Hospital Anxiety and Depression Scale were
      significantly improved in the intervention group compared to the control group
      (Barthel Index mean: from 31.7 +/- 5.9 to 97.2 +/- 2.8 vs from 33.2 +/- 4.8 to
      76.4 +/- 9.4, P < 0.001; Hospital Anxiety and Depression Scale mean: from 16.1 +/
      7.6 to 9.1 +/- 0.3 vs 16.4 +/- 4.9 to 9.1 +/- 0.3, P= 0.003). Depression was
      strongly associated with being dependent on others. However, the Thai Mini-Mental
      State Examination in both groups did not significantly differ (Thai Mini-Mental
      State Examination mean: from 24.4 +/- 2.0 to 24.6 vs 23.8 +/- 1.9 to 24.1 +/-
      0.3, P= 0.068). There was no significant interaction between baseline
      characteristics and treatment outcome. CONCLUSIONS: At 2 years follow-up, it was
      evident that a 6-month home rehabilitation programme after ischemic stroke
      improved functional outcome and reduced incidence of depression, but not
      dementia.

PMID- 22994619
TI  - Classification of delusions in Alzheimer's disease and their neural correlates.
AB  - BACKGROUND: Previous findings on neural correlates of delusion in Alzheimer's
      disease (AD) have been inconsistent because of methodological issues, such as
      treating multiple delusions as a single entity. In this retrospective study, we
      classified AD delusions and investigated their neural correlates by using single
      photon emission computed tomography data. METHODS: We selected AD patients with
      delusions from our consecutive outpatients from 2004 to 2010. In this study,
      eight types of delusions were evaluated with Neuropsychiatric Inventory and
      classified by factor analysis. Twenty-five of the patients also had single-photon
      emission computed tomography data, which we used to assess the relationships
      between cerebral regions of hypoperfusion and hyperperfusion and each classified
      delusion. The relations were assessed using Statistical Parametric Mapping with
      normalization to the white matter cerebral blood flow. RESULTS: The delusions
      were classified into three factors. Factor 1 consisted of a belief that his/her
      house is not his/her home, phantom boarder symptom, delusion of abandonment, and
      belief that one's spouse or others are not who they claim to be. Factor 1 was
      related to hypoperfusion in the right temporal pole and hyperperfusion in the
      medial frontal and precentral regions. Factor 2 consisted of delusion relating to
      the television and delusion of persecution. Factor 2 was related to hypoperfusion
      in the precuneus and hyperperfusion in the insula and thalamus. Factor 3
      consisted of delusion of abandonment and delusional jealousy. Factor 3 was
      related to hypoperfusion in the right inferior temporal and frontal regions and
      hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus.
      Delusion of theft was not included in any factors, and it was related to
      hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and
      hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus.
      CONCLUSIONS: Delusions in AD were classifiable, and each classified delusion was
      related to different neural networks.

PMID- 22994620
TI  - Delayed onset and prolonged interictal delirium following electroconvulsive
      therapy.
AB  - Electroconvulsive therapy is safe and effective in the treatment of depression in
      older individuals. Minor cognitive side effects of electroconvulsive therapy
      include acute postictal confusion and reversible short-term memory deficits.
      However, interictal delirium is uncommon in absence of risk factors. Herein, we
      report the case a depressed male patient without any known risk factors who
      developed interictal delirium 2 days after his sixth electroconvulsive therapy
      session. Interictal delirium improved with treatment within 1 week.

PMID- 22994621
TI  - Is anticholinergic activity related with Parkinson's disease?

PMID- 22994623
TI  - Platelet microRNAs: From platelet biology to possible disease biomarkers and
      therapeutic targets.
AB  - Although anucleated, platelets contain megakaryocyte-derived messenger
      ribonucleic acid (mRNA) which can be translated to produce protein molecules.
      Recently, platelets have been found to contain small (~23 base pair) non-coding
      microRNAs (miRNAs) derived from hairpin-like precursors. MiRNAs can specifically
      silence their mRNA targets regulating mRNA translation. Platelet miRNAs are
      reported to bind to important platelet target mRNAs involved in platelet
      reactivity including P2Y12 ADP receptor, GPIIb receptor, and cyclic AMP-dependent
      protein kinase A. They also regulate important functions such as platelet shape
      change, granules secretion, and platelet activation. Platelet miRNAs were also
      proposed as biomarkers of arteriosclerosis, although their role in vascular
      inflammation needs to be elucidated. Further, the possibility of using miRNAs as
      therapeutic tools has emerged. Using synthetic oligo-nucleotides that antagonize
      miRNAs binding to their mRNAs-targets or synthetic miRNAs mimics that enhance
      endogenous miRNAs function potentially will ultimately lead to the manipulation
      of platelet miRNAs expression and function with significant effects on specific
      protein levels and overall platelet reactivity. 

PMID- 22994622
TI  - Copy number amplification of the PIK3CA gene is associated with poor prognosis in
      non-lymph node metastatic head and neck squamous cell carcinoma.
AB  - BACKGROUND: Deregulation of the EGFR signaling pathway is one of the most
      frequently observed genetic abnormalities that drives cancer development.
      Although mutations in the downstream components of the EGFR signaling pathway,
      including KRAS, BRAF and PIK3CA, have been reported in numerous cancers,
      extensive mutation and copy number analysis of these genes in clinical samples
      has not been performed for head and neck squamous cell carcinoma (HNSCC).
      METHODS: We examined the mutations and copy number alterations of KRAS, BRAF and
      PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated
      patients.We used DNA sequencing to detect mutations and the copy number changes
      were evaluated by qPCR and array comparative genomic hybridization (CGH)
      analysis. RESULTS: We examined the mutations and copy number alterations of KRAS,
      BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically
      treated patients. We identified 3 mutations (2.6%) in K-RAS and 3 mutations
      (2.6%) in PIK3CA. Copy number amplification was found in 37 cases (32.2%) for
      PIK3CA, 10 cases (8.7%) for K-RAS and 2 cases (1.7%) for BRAF. Kaplan-Meier
      survival analysis revealed that copy-number amplification of PIK3CA was markedly
      associated with cancer relapse in patients without lymph node metastasis. (Log
      rank test, p = 0.026) CONCLUSIONS: Copy number amplification of the PIK3CA gene
      is associated with poor prognosis in HNSCC patients without lymph node
      metastasis. The PIK3CA copy number status will serve as a marker of poor
      prognosis in patients with HNSCC.

PMID- 22994625
TI  - Abstracts of the 38th Annual Meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD). October 10-13, 2012. Istanbul, Turkey.

PMID- 22994624
TI  - Selective functionalization of tailored nanostructures.
AB  - The controlled positioning of nanostructures with active molecular components is
      of importance throughout nanoscience and nanotechnology. We present a novel three
      step method to produce nanostructures that are selectively decorated with
      functional molecules. We use fluorophores and nanoparticles to functionalize SiO
      features with defined shapes and with sizes ranging from micrometers to 25 nm.
      The method is called MACE-ID: molecular assembly controlled by electron-beam
      induced deposition. In the first step, SiO nanostructures are written with
      focused electron-beam-induced deposition, a direct-writing technique. In the
      second step, the deposits are selectively silanized. In the final step, the
      silanes are functionalized with fluorescent dyes, polystyrene spheres, or gold
      nanoparticles. This recipe gives exciting new possibilities for combining the
      highly accurate control of top-down patterning (e-beam direct writing) with the
      rich variety of the bottom-up approach (self-assembly), leading to active or
      responsive surfaces. An important advantage of MACE-ID is that it can be used on
      substrates that already contain complex features, such as plasmonic structures,
      nanoantennas, and cavities.

PMID- 22994627
TI  - Tandem application of C-C bond-forming reactions with reductive ozonolysis.
AB  - Several variants of reductive ozonolysis, defined here as the in situ generation
      of aldehydes or ketones during ozonolytic cleavage of alkenes, are demonstrated
      to work effectively in tandem with a number of C-C bond-forming reactions. For
      reactions involving basic nucleophiles (1,2-addition of Grignard reagents, Wittig
      or Horner-Emmons olefinations, and directed aldol reactions of lithium enolates),
      the one-pot process offers a rapid and high-yielding alternative to traditional
      two-step protocols.

PMID- 22994626
TI  - Evolutionary insights into scleractinian corals using comparative genomic
      hybridizations.
AB  - BACKGROUND: Coral reefs belong to the most ecologically and economically
      important ecosystems on our planet. Yet, they are under steady decline worldwide
      due to rising sea surface temperatures, disease, and pollution. Understanding the
      molecular impact of these stressors on different coral species is imperative in
      order to predict how coral populations will respond to this continued
      disturbance. The use of molecular tools such as microarrays has provided deep
      insight into the molecular stress response of corals. Here, we have performed
      comparative genomic hybridizations (CGH) with different coral species to an
      Acropora palmata microarray platform containing 13,546 cDNA clones in order to
      identify potentially rapidly evolving genes and to determine the suitability of
      existing microarray platforms for use in gene expression studies (via
      heterologous hybridization). RESULTS: Our results showed that the current
      microarray platform for A. palmata is able to provide biological relevant
      information for a wide variety of coral species covering both the complex clade
      as well the robust clade. Analysis of the fraction of highly diverged genes
      showed a significantly higher amount of genes without annotation corroborating
      previous findings that point towards a higher rate of divergence for
      taxonomically restricted genes. Among the genes with annotation, we found many
      mitochondrial genes to be highly diverged in M. faveolata when compared to A.
      palmata, while the majority of nuclear encoded genes maintained an average
      divergence rate. CONCLUSIONS: The use of present microarray platforms for
      transcriptional analyses in different coral species will greatly enhance the
      understanding of the molecular basis of stress and health and highlight
      evolutionary differences between scleractinian coral species. On a genomic basis,
      we show that cDNA arrays can be used to identify patterns of divergence.
      Mitochondrion-encoded genes seem to have diverged faster than nuclear encoded
      genes in robust corals. Accordingly, this needs to be taken into account when
      using mitochondrial markers for scleractinian phylogenies.

PMID- 22994628
TI  - Purification and characterization of a novel angiotensin I-converting enzyme
      inhibitory peptide derived from an enzymatic hydrolysate of duck skin byproducts.
AB  - An angiotensin I-converting enzyme (ACE) inhibitory peptide was isolated and
      identified from hydrolysates of duck skin byproducts. Duck skin byproducts were
      hydrolyzed using nine proteases (Alcalase, Collagenase, Flavourzyme, Neutrase,
      papain, pepsin, Protamex, trypsin, and alpha-chymotrypsin) to produce an
      antihypertensive peptide. Of the various hydrolysates produced, the alpha
      chymotrypsin hydrolysate exhibited the highest ACE inhibitory activity. The
      hydrolysate was purified using fast protein liquid chromatography (FPLC) and high
      performance liquid chromatography (HPLC). The amino acid sequence of the ACE
      inhibitory peptide was identified as a hexapeptide Trp-Tyr-Pro-Ala-Ala-Pro, with
      a molecular weight of 693.90 Da. The peptide had an IC50 value of 137 MUM, and
      the inhibitory pattern of the purified ACE inhibitor from duck skin byproducts
      was determined to be competitive by Lineweaver-Burk plots. In addition, the
      peptide was synthesized and the ACE inhibitory activity was verified in vivo.
      Spontaneously hypertensive rats (SHR) exhibited significantly decreased blood
      pressure and heart rate after peptide injection. Taken together, the results
      suggest that Trp-Tyr-Pro-Ala-Ala-Pro may be useful as a new antihypertensive
      agent. 

PMID- 22994629
TI  - Peer network overlap in twin, sibling, and friend dyads.
AB  - Research suggests that sibling-peer connections are important for understanding
      adolescent problem behaviors. Using a novel behavioral genetic design, the
      current study investigated peer network overlap in 300 child-child pairs (aged 7
      13 years) in 5 dyad types: monozygotic (MZ), dizygotic twins, full siblings
      (FSs), friend pairs, and virtual twins (i.e., same-aged, genetically unrelated
      siblings). Genetic relatedness, sex composition, and age differences contributed
      to peer overlap in sibling dyads. MZ twins showed the highest overlap (82%),
      opposite-sex FS pairs showed the lowest overlap (27%), and friend pairs (48%)
      were close to the mean (53%). Social contact variables and self-reported
      relationship intimacy predicted additional variance in peer overlap. The roles of
      genotype-environment correlational and shared environmental processes in the
      sibling-peer connections are discussed.

PMID- 22994630
TI  - Infibulated women have an increased risk of anal sphincter tears at delivery: a
      population-based Swedish register study of 250 000 births.
AB  - OBJECTIVE: To investigate the risk for anal sphincter tears (AST) in infibulated
      women. DESIGN: Population-based cohort study. SETTING: Nationwide study in
      Sweden. POPULATION: The study population included 250 491 primiparous women with
      a vaginal singleton birth at 37-41 completed gestational weeks during 1999-2008.
      We only included women born in Sweden and in Africa. The African women were
      categorized into three groups; a Somalia group, n = 929, where over 95% are
      infibulated; the Eritrea-Ethiopia-Sudan group, n = 955, where the majority are
      infibulated, compared with other African countries, n = 1035, where few
      individuals are infibulated but had otherwise similar anthropometric
      characteristics. These women were compared with 247 572 Swedish-born women.
      METHODS: Register study with data from the National Medical Birth Registry. MAIN
      OUTCOME MEASURES: AST in non-instrumental and instrumental vaginal delivery.
      RESULTS: Compared with Swedish-born women, women from Somalia had the highest
      odds ratio for AST in all vaginal deliveries: 2.72 (95%CI 2.08-3.54), followed by
      women from Eritrea-Ethiopia-Sudan 1.80 (1.41-2.32) and other African countries
      1.23 (0.89-1.53) after adjustment for major risk factors. Mediolateral episiotomy
      was associated with a reduced risk of AST in instrumental deliveries. CONCLUSION:
      Delivering African women from countries where infibulation is common carries an
      increased risk of AST compared with Swedish-born women, despite delivering in a
      highly technical quality healthcare setting. AST can cause anal incontinence and
      it is important to investigate risk factors for this and try to improve clinical
      routines during delivery to reduce the incidence of this complication.

PMID- 22994631
TI  - Patterns of electronic cigarette use and user beliefs about their safety and
      benefits: an internet survey.
AB  - INTRODUCTION AND AIMS: As the popularity of electronic cigarettes (e-cigarettes)
      increases, it is becoming important to find out more about the characteristics of
      e-cigarette users, why and how they use the product and whether e-cigarettes are
      used exclusively or in combination with conventional cigarettes. The objective of
      this study was to investigate patterns and effects of e-cigarette use and user
      beliefs about e-cigarette safety and benefits. DESIGN AND METHODS: E-cigarette
      users in Poland were recruited online and asked to participate in a web-based
      survey. The participants provided information on their smoking history, patterns
      of e-cigarette use, beliefs and attitudes regarding the product and information
      on concurrent use of conventional cigarettes. RESULTS: The survey was completed
      by 179 e-cigarette users. Almost all participants used e-cigarettes daily. E
      cigarettes were primarily used to quit smoking or to reduce the harm associated
      with smoking (both 41%), and were successful in helping the surveyed users to
      achieve these goals with 66% not smoking conventional cigarettes at all and 25%
      smoking under five cigarettes a day. Most participants (82%) did not think that e
      cigarettes were completely safe, but thought that they were less dangerous than
      conventional cigarettes. Sixty percent believed that e-cigarettes were addictive,
      but less so than conventional cigarettes. DISCUSSION AND CONCLUSIONS: The
      participants primarily used e-cigarettes as a stop-smoking aid or as an
      alternative to conventional cigarettes, and the majority reported that they
      successfully stopped smoking. More data on e-cigarette safety and its efficacy in
      harm-reduction and smoking cessation are needed.

PMID- 22994632
TI  - Silencing of tomato RBOH1 and MPK2 abolishes brassinosteroid-induced H2O2
      generation and stress tolerance.
AB  - Brassinosteroids (BRs) are involved in the regulation of plant growth,
      development and stress responses. While the signalling pathways for BR-regulated
      plant growth and development are well studied, the mechanisms by which BRs
      regulate plant stress tolerance remain largely unclear. Here we showed that 24
      epibrassinolide (EBR), which induced tolerance to oxidative and heat stress in
      tomato, was also capable of elevating the transcript levels of RBOH1, MPK1 and
      MPK2, increasing apoplastic H2 O2 accumulation, and enhancing activation of
      MPK1/2. Virus-induced gene silencing of RBOH1, MPK1, MPK2 and MPK1/2 resulted in
      reduced stress tolerance. Silencing of RBOH1 had no effect on the transcripts of
      MPK1 and MPK2 but inhibited MPK1/2 activation and H2 O2 accumulation. Silencing
      of either MPK1 or MPK2, on the other hand, reduced RBOH1 transcript, H2 O2
      accumulation and MPK1/2 activity. BR-induced tolerance and MPK1/2 activation were
      compromised in RBOH1-, MPK2- and MPK1/2-silenced plants but not in MPK1-silenced
      plants. These results suggested that MPK2 played a more critical role than MPK1
      in EBR-induced apoplastic H2 O2 accumulation. RBOH1, MPK1 and MPK2 were involved
      in the stress tolerance and BR-induced stress tolerance likely involved a
      positive feedback loop among RBOH1, H2 O2 and MPK2, leading to sustained
      apoplastic accumulation of H2 O2 and related signalling processes.

PMID- 22994633
TI  - Is bariatric surgery really inefficient in hypothalamic obesity?

PMID- 22994634
TI  - A randomised, blinded, crossover study to assess the efficacy of a feed
      supplement in alleviating the clinical signs of headshaking in 32 horses.
AB  - REASONS FOR PERFORMING STUDY: Feed supplements are commonly used by owners to
      alleviate headshaking; however, randomised, controlled trials are required to
      assess their efficacy. OBJECTIVE: To determine the efficacy of a feed supplement
      for alleviation of the clinical signs of headshaking using a randomised, blinded,
      placebo-controlled trial. METHODS: Using a crossover design, 44 horses previously
      diagnosed with chronic idiopathic headshaking received both the supplement and a
      matching placebo per os for 28 days with a washout period between of 14 days.
      Video recordings were taken at rest and exercise prior to the study and at the
      end of both periods of treatment. The degree of headshaking was assessed in a
      blinded, randomised manner by 2 veterinary surgeons. At the same time points,
      owners completed a questionnaire to assess the severity of headshaking signs. A
      Wilcoxon signed rank test was used to compare the scores while on supplement and
      placebo. RESULTS: Using the video assessments, there was no significant
      difference between scores while on supplement compared with placebo (P = 0.7).
      Using the questionnaire responses, there was no significant difference between
      scores for any activity when the placebo and the supplement were compared with
      each other. However, owners reported significant improvement during all
      activities for both placebo and supplement compared with pretreatment scores.
      CONCLUSIONS AND POTENTIAL RELEVANCE: The supplement offered no benefit over a
      placebo in alleviating the clinical signs of headshaking. There appeared to be a
      significant proxy placebo effect when the outcome was based on subjective owner
      perception of clinical signs. This study demonstrated no beneficial effect of
      this supplement on the clinical signs of headshaking. The study did show a
      significant placebo effect, thereby highlighting the necessity of properly
      conducted, randomised controlled trials, with blinding, to assess true treatment
      effects in trials in animals.

PMID- 22994635
TI  - Meeting the challenge of feeding 9 billion people safely and securely.

PMID- 22994636
TI  - Lessons learned from the child agricultural labor law debate.

PMID- 22994637
TI  - The consequences of noise-induced hearing loss on dairy farm communities in New
      Zealand.
AB  - The objective of this study was to investigate how noise-induced hearing loss
      (NIHL) or noise injury (NI) affects individuals and others of dairy farm
      communities in New Zealand. Using "grab" or opportunistic sampling at DairyNZ
      discussion groups and a recreational function, a survey questionnaire was
      completed by 74 participants from two dairy farming communities in New Zealand.
      Self-reported hearing difficulties were highlighted by 48% (42) of the 74
      participants. The effects of NI on individuals and others included communication
      difficulties leading to the development of coping strategies, social isolation;
      decreased employment opportunities, loss of productivity, and increased effort
      and adjustments by family and work colleagues. Frustration, anxiety, stress,
      resentment, depression, and fatigue are also negative consequences that may
      contribute to a loss of quality of life and contribute to further health costs.
      Increased lateness, absenteeism, sickness and other behavioral aspects were not
      expressed as normal issues in the workplace, as the majority of the individuals
      are/were self-employed or working in a family business. This study shows that
      each year in New Zealand NI results in significant negative social,
      psychological, and economic consequences for those individuals affected, along
      with their families, friends, and work colleagues.

PMID- 22994638
TI  - Swedish dairy farmers' perceptions of animal-related injuries.
AB  - Animal-related injuries are among the most common occupational injuries in
      agriculture. Despite the large number of documented animal-related injuries in
      dairy farming, the issue has received relatively limited attention in the
      scientific literature. The farmers' own perspectives and views on risks and
      safety during livestock handling and what they think are effective ways of
      preventing injuries are valuable for the future design of effective
      interventions. This paper presents results from a qualitative study with the aim
      to investigate Swedish dairy farmers' own experience of animal-related
      occupational injuries, as well as their perceptions of and attitudes towards
      them, including risk and safety issues, and prevention measures. A total of 12
      dairy farmers with loose housing systems participated in the study. Data
      collection was conducted by means of semistructured in-depth interviews. Three
      main themes with an impact on risks and safety when handling cattle were
      identified: the handler, the cattle, and the facilities. They all interact with
      each other, influencing the potential risks of any work task. Most of the farmers
      believed that a majority of the injuries can be prevented, but there are always
      some incidents that are impossible to foresee. In conclusion, this study
      indicates that Swedish dairy farmers are aware of the dangers from working with
      cattle. However, even though safety is acknowledged by the farmers as an
      important and relevant issue, in the end safety is often forgotten or not
      prioritized. One concern is that farmers are willing to take calculated risks to
      save money or time. In situations where they work alone with high stress levels
      and under economic distress, safety issues are easily given low priority.

PMID- 22994639
TI  - Midwest growers' mail survey of contributors to migrant health and nutrition.
AB  - The purpose of this study was to solicit information from farm owners (growers),
      as representatives of their farm businesses, regarding descriptive information on
      migrant camp housing that may contribute to the health and nutritional status of
      employed workers and their families. This cross-sectional descriptive mail survey
      was sent to 802 growers in Indiana, Michigan, Ohio, and Pennsylvania via the US
      Postal Service. The growers were identified by an Internet search for licensed
      agricultural work camps in Midwest departments of agriculture. Response rate was
      34%. Overall, growers reported a median of one migrant camp with 23 residents,
      employing workers seasonally for either 10 weeks or 6 months, with seven
      accompanying children on site. Individual kitchen appliances varied across the
      states, potentially influencing the preparation of healthy meals. Three themes
      were identified from the results. First, over one third of owners lacked or had
      limited knowledge about the health services available to migrant families.
      Second, migrant workers may have limited access to a variety of fresh produce for
      household meal preparation. Third, migrant children were unable to easily access
      public play areas, and families lacked recreational spaces in agricultural work
      camps. Play areas in migrant camps were mostly identified as open fields with
      little play equipment on site. Knowledge learned can influence future
      agricultural camp practices and the design of future research studies, and
      provide direction for grower education topics presented at agricultural
      conferences and by extension services.

PMID- 22994640
TI  - Mobile farm clinic outreach to address health conditions among Latino migrant
      farmworkers in Georgia.
AB  - Agricultural labor involves exposure to many occupational hazards, some of which
      can lead to chronic health conditions. The purpose of this study was to conduct
      an occupational health needs assessment of illnesses and work-related injuries
      among a Latino migrant farmworker population (recruited to harvest Vidalia
      onions) in South Georgia. Study data included survey responses from 100
      farmworkers attending mobile farm clinics in 2010 at their worker housing
      residences, supplemented by medical diagnoses data from the same clinics
      collected over 3 years (2009-2011) for 1161 farmworkers at six different farms.
      From the survey, the main health problems reported were hypertension (25%), eye
      problems (12%), musculoskeletal problems (11%), diabetes (10%), and depression
      (7%). In multivariate analyses, depression scores were associated with having a
      history of musculoskeletal problems (p = .002). According to the mobile farm
      clinic data, the most common medical diagnoses included back pain (11.8%),
      hypertension (11.4%), musculoskeletal problems (11.3%), gastrointestinal
      disorders (8.6%), eye problems (7.2%), dermatitis or rash (7.0%), and tinea or
      fungal skin infections (5.6%). The study identified eye and musculoskeletal
      problems as the major occupational health conditions for this population of
      farmworkers.

PMID- 22994641
TI  - Action Learning: a new method to increase tractor rollover protective structure
      (ROPS) adoption.
AB  - Action Learning is a problem-solving process that is used in various industries
      to address difficult problems. This project applied Action Learning to a leading
      problem in agricultural safety. Tractor overturns are the leading cause of fatal
      injury to farmworkers. This cause of injury is preventable using rollover
      protective structures (ROPS), protective equipment that functions as a roll bar
      structure to protect the operator in the event of an overturn. For agricultural
      tractors manufactured after 1976 and employee operated, Occupational Safety and
      Health Administration (OSHA) regulation requires employers to equip them with
      ROPS and seat belts. By the mid-1980s, US tractor manufacturers began adding ROPS
      on all farm tractors over 20 horsepower sold in the United States
      (http://www.nasdonline.org/document/113/d001656/rollover-protection-for-farm
      tractor-operators.html). However, many older tractors remain in use without ROPS,
      putting tractor operators at continued risk for traumatic injury and fatality.
      For many older tractor models ROPS are available for retrofit, but for a variety
      of reasons, tractor owners have not chosen to retrofit those ROPS. The National
      Institute for Occupational Safety and Health (NIOSH) attempted various means to
      ameliorate this occupational safety risk, including the manufacture of a low-cost
      ROPS for self-assembly. Other approaches address barriers to adoption. An Action
      Learning approach to increasing adoption of ROPS was followed in Virginia and New
      York, with mixed results. Virginia took action to increase the manufacturing and
      adoption of ROPS, but New York saw problems that would be insurmountable.
      Increased focus on team composition might be needed to establish effective Action
      Learning teams to address this problem.

PMID- 22994642
TI  - Twenty years of AgrAbility: a retrospective forum.
AB  - In 1990, the Farm Bill included authorization for the Education and Training
      Assistance Program for Farmers with Disabilities with the goal of enabling a high
      quality lifestyle for farmers, ranchers, and other agricultural workers with
      disabilities. Twenty years later, AgrAbility is a developed national program with
      25 state projects and affiliates throughout the United States and strong
      recognition with the rural and disability communities. A special forum was held
      in Washington, DC, last September to celebrate AgrAbility's achievements.
      Clients, staff members, advisory team members, government officials, and guests
      joined to discuss future plans for the program. Recommendations were considered
      to broaden the effect of the program and to enhance access to program services,
      especially in states without funded programs. This article summarizes key
      outcomes from this event.

PMID- 22994643
TI  - Informal occupational safety information exchange among Latino migrant and
      seasonal farmworkers.
AB  - Latino farmworkers in North Carolina are a hard-to-reach population that faces
      diverse occupational health risks, including pesticide exposure. Health and
      safety education efforts often employ lay health advisor or promotor(a) de salud
      models in which farmworker community members are trained to provide health
      education. As a frequently tight-knit and isolated group, farmworkers may be well
      suited to serve as resident lay health advisors. This paper presents data
      collected from a nonrandom sample of Latino farmworkers living in North Carolina
      regarding the natural level of occupational safety information exchange among
      Latino farmworkers, specifically pesticide safety information. The data affirm
      that farmworkers informally exchange occupational safety information with one
      another, with the level of exchange increasing during the agricultural season.
      Consequently, if trained, the data suggest that farmworkers might be situated to
      provide in situ occupational health and safety education to their peers. This
      remains to be systematically tested and evaluated.

PMID- 22994644
TI  - Safety features on agricultural machines and farm structures in Saskatchewan.
AB  - Major injury is an important occupational health problem for farming populations
      in North America. There are several well-established risk factors for injury in
      this setting, including lack of safety features on farm vehicles and machinery,
      and a lack of passive safety devices that offer protection from falls and
      drowning events. Through the examination of common risk factors, the authors
      demonstrate that substantial proportions of farms in Saskatchewan, Canada, are
      exposed to occupational hazards that leave workers and others vulnerable to major
      injury.

PMID- 22994647
TI  - Dental usage under changing economic conditions.
AB  - OBJECTIVE: The purpose of this article is to examine the relationship between
      changes in household finances (wealth and income) and changes in dental
      utilization at the onset of the recent recession in a population of older
      Americans. METHODS: Data from the Health and Retirement Study (HRS) were analyzed
      for U.S. individuals aged 51 years and older during the 2006 and 2008 waves of
      the HRS. We estimated logistic models of (a) starting and (b) stopping dental use
      between 2006 and 2008 survey periods as a function of changes in household wealth
      and income, controlling for other potentially confounding covariates. RESULTS: We
      found that only when household wealth falls by 50 percent or more were older
      adults less likely to seek dental care. Changes in household income and other
      changes in household wealth were not associated with changes in dental
      utilization among this population. CONCLUSIONS: Older Americans' dental care
      utilization appeared to be fairly resilient to changes in household finances;
      only when wealth fell by 50 percent or more did individuals decrease dental use.
      This finding might extend to other health-care services that are preventive,
      routine, and relatively inexpensive.

PMID- 22994648
TI  - Effect of a vascular access surveillance program on service provision and access
      thrombosis.
AB  - Establishing and maintaining hemodialysis access are major challenges in dialysis
      patient care. The impact of implementing guideline recommendations around
      vascular access surveillance, which lacks strong evidence, is poorly understood.
      We report the results of a vascular access surveillance and early intervention
      program upon hemodialysis thrombosis rates for all patients hemodialyzing in a
      single center between January 2005 and March 2011. Data were derived from
      hospital records and the Australian and New Zealand Dialysis and Transplant
      Registry (ANZDATA). Data were collected of 227 prevalent patients over the 6-year
      period. Crude ultrasound and angiography intervention rates increased from 23 and
      57 per 100 prevalent patients per quarter (/100 pts/qtr) to 31 and 83/100
      pts/qtr, respectively, during the study. Crude thrombosis rates fell from 21 to
      2/100 pts/qtr during the study. After adjustment for comorbidities, mean
      ultrasound use increased by 4.6% per quarter (95% CI: 2.4-6.9, p<0.001), mean
      interventional angiography increased by 2.6% per quarter (95% CI: 1.1-4.2,
      p=0.001), and the predicted mean of the number of thromboses decreased by 8.4%
      per quarter (95% CI: 5.6-11.1, p<0.001). Implementation of a vascular access
      surveillance increases service utilization and is associated with a reduction in
      vascular access thrombosis.

PMID- 22994649
TI  - Evolutionary relationships of flavobacterial and enterobacterial endosymbionts
      with their scale insect hosts (Hemiptera: Coccoidea).
AB  - Flavobacteria and Enterobacteriaceae have been previously reported as scale
      insect endosymbionts. The purpose of this work was twofold: first, to screen
      different scale insect families for the presence of these endosymbionts by PCR
      analyses and second, to elucidate the history of cophylogeny between these
      bacteria and the insects by analysing a portion of 16S rRNA and 18S rRNA gene
      sequences by two reconciliation tools, CoRe-PA and Jane. From a survey of 27
      scale insects within seven families, we identified Flavobacteria and
      Enterobacteriaceae as coexisting in ten species that belong to the Ortheziidae,
      Monophlebidae, Diaspididae and Coccidae families, and we frequently found two
      closely related enterobacteria harboured in the same individual. Analyses
      performed with CoRe-PA and Jane suggest that Flavobacteria from the scale insects
      analysed have a unique origin, except for Candidatus Brownia rhizoecola
      (Flavobacteria of Pseudococcidae, Phenacoccinae), which seems to come from a
      nonscale insect. Nevertheless, cospeciation between Flavobacteria and scale
      insects is suggested only within the families Monophlebidae, Ortheziidae and
      Diaspididae, and host switches seem to have occurred from the ancestors of
      Monophlebidae and Ortheziidae to insects from families Coccidae,
      Lecanodiaspididae, Eriococcidae and Pseudococcidae. Our analyses suggest that
      Enterobacteriaceae underwent more evolutionary events (losses, duplications and
      host switches), and their phylogenies showed a lower proportion of congruent
      nodes between host and bacteria, indicating a more relaxed relationship with
      scale insects compared with Flavobacteria.

PMID- 22994650
TI  - DANA: distributed numerical and adaptive modelling framework.
AB  - DANA is a python framework ( http://dana.loria.fr ) whose computational paradigm
      is grounded on the notion of a unit that is essentially a set of time dependent
      values varying under the influence of other units via adaptive weighted
      connections. The evolution of a unit's value are defined by a set of differential
      equations expressed in standard mathematical notation which greatly ease their
      definition. The units are organized into groups that form a model. Each unit can
      be connected to any other unit (including itself) using a weighted connection.
      The DANA framework offers a set of core objects needed to design and run such
      models. The modeler only has to define the equations of a unit as well as the
      equations governing the training of the connections. The simulation is completely
      transparent to the modeler and is handled by DANA. This allows DANA to be used
      for a wide range of numerical and distributed models as long as they fit the
      proposed framework (e.g. cellular automata, reaction-diffusion system,
      decentralized neural networks, recurrent neural networks, kernel-based image
      processing, etc.).

PMID- 22994652
TI  - Recurrent hepatocellular carcinoma after liver transplantation - an emerging
      clinical challenge.
AB  - In western countries, hepatocellular carcinoma (HCC) is a major reason for
      orthotopic liver transplantation (OLT) with estimated recurrence rates between
      15% and 20%. This selective literature review addresses follow-up care after OLT
      in HCC and current treatment options. Recurrence prediction is based on
      pathological tumor stage, vascular invasion, serum alfafetoprotein levels, and
      histological differentiation, but further advances are expected by molecular
      profiling techniques. Lower levels of immunosuppressive agents are associated
      with a lower risk for HCC recurrence. Retrospective studies indicate that
      mammalian target of rapamycin (mTOR) inhibitors as immunosuppression reduce the
      risk of HCC recurrence. However, prospective studies supporting this potential
      advantage of mTOR inhibitors are still lacking, and higher rejection rates were
      reported for sirolimus after OLT in HCC. Prognosis is poor in recurrent HCC, a
      longer interval between OLT and recurrence and feasibility of surgical resection
      are associated with improved survival. Systemic treatment with sorafenib is the
      current standard of care in patients with advanced-stage HCC not suitable for
      locoregional therapy. After OLT, combination of an mTOR inhibitor with sorafenib
      is feasible and frequently used in clinical practice. As safety and efficacy data
      are still limited, close clinical monitoring is mandatory.

PMID- 22994651
TI  - Iliotibial band syndrome in runners: a systematic review.
AB  - BACKGROUND: The popularity of running is still growing and, as participation
      increases, the incidence of running-related injuries will also rise. Iliotibial
      band syndrome (ITBS) is the most common injury of the lateral side of the knee in
      runners, with an incidence estimated to be between 5% and 14%. In order to
      facilitate the evidence-based management of ITBS in runners, more needs to be
      learned about the aetiology, diagnosis and treatment of this injury. OBJECTIVE:
      This article provides a systematic review of the literature on the aetiology,
      diagnosis and treatment of ITBS in runners. SEARCH STRATEGY: The Cochrane
      Library, MEDLINE, EMBASE, CINAHL, Web of Science, and reference lists were
      searched for relevant articles. SELECTION CRITERIA: Systematic reviews, clinical
      trials or observational studies involving adult runners (>18 years) that focused
      on the aetiology, diagnosis and/or treatment of ITBS were included and articles
      not written in English, French, German or Dutch were excluded. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently screened search results, assessed
      methodological quality and extracted data. The sum of all positive ratings
      divided by the maximum score was the percentage quality score (QS). Only studies
      with a QS higher than 60% were included in the analysis. The following data were
      extracted: study design; number and characteristics of participants; diagnostic
      criteria for ITBS; exposure/treatment characteristics; analyses/outcome variables
      of the study; and setting and theoretical perspective on ITBS. MAIN RESULTS: The
      studies of the aetiology of ITBS in runners provide limited or conflicting
      evidence and it is not clear whether hip abductor weakness has a major role in
      ITBS. The kinetics and kinematics of the hip, knee and/or ankle/foot appear to be
      considerably different in runners with ITBS to those without. The biomechanical
      studies involved small samples, and data seem to have been influenced by sex,
      height and weight of participants. Although most studies monitored the management
      of ITBS using clinical tests, these tests have not been validated for this
      patient group. While the articles were inconsistent regarding the treatment of
      ITBS, hip/knee coordination and running style appear to be key factors in the
      treatment of ITBS. Runners might also benefit from mobilization, exercises to
      strengthen the hip, and advice about running shoes and running surface.
      CONCLUSION: The methodological quality of research into the management of ITBS in
      runners is poor and the results are highly conflicting. Therefore, the study
      designs should be improved to prevent selection bias and to increase the
      generalizability of findings.

PMID- 22994653
TI  - High abundance of Serine/Threonine-rich regions predicted to be hyper-O
      glycosylated in the secretory proteins coded by eight fungal genomes.
AB  - BACKGROUND: O-glycosylation of secretory proteins has been found to be an
      important factor in fungal biology and virulence. It consists in the addition of
      short glycosidic chains to Ser or Thr residues in the protein backbone via O
      glycosidic bonds. Secretory proteins in fungi frequently display Ser/Thr rich
      regions that could be sites of extensive O-glycosylation. We have analyzed in
      silico the complete sets of putatively secretory proteins coded by eight fungal
      genomes (Botrytis cinerea, Magnaporthe grisea, Sclerotinia sclerotiorum, Ustilago
      maydis, Aspergillus nidulans, Neurospora crassa, Trichoderma reesei, and
      Saccharomyces cerevisiae) in search of Ser/Thr-rich regions as well as regions
      predicted to be highly O-glycosylated by NetOGlyc (http://www.cbs.dtu.dk).
      RESULTS: By comparison with experimental data, NetOGlyc was found to overestimate
      the number of O-glycosylation sites in fungi by a factor of 1.5, but to be quite
      reliable in the prediction of highly O-glycosylated regions. About half of
      secretory proteins have at least one Ser/Thr-rich region, with a Ser/Thr content
      of at least 40% over an average length of 40 amino acids. Most secretory proteins
      in filamentous fungi were predicted to be O-glycosylated, sometimes in dozens or
      even hundreds of sites. Residues predicted to be O-glycosylated have a tendency
      to be grouped together forming hyper-O-glycosylated regions of varying length.
      CONCLUSIONS: About one fourth of secretory fungal proteins were predicted to have
      at least one hyper-O-glycosylated region, which consists of 45 amino acids on
      average and displays at least one O-glycosylated Ser or Thr every four residues.
      These putative highly O-glycosylated regions can be found anywhere along the
      proteins but have a slight tendency to be at either one of the two ends.

PMID- 22994654
TI  - Beta-adrenergic receptor polymorphisms and cardiac graft function in potential
      organ donors.
AB  - Prior studies have demonstrated associations between beta-adrenergic receptor
      (betaAR) polymorphisms and left ventricular dysfunction-an important cause of
      allograft nonutilization for transplantation. We hypothesized that betaAR
      polymorphisms predispose donor hearts to LV dysfunction after brain death. A
      total of 1043 organ donors managed from 2001-2006 were initially studied. The
      following betaAR single nucleotide polymorphisms were genotyped: beta1AR 1165C/G
      (Arg389Gly), beta1AR 145A/G (Ser49Gly), beta2AR 46G/A (Gly16Arg) and beta2AR
      79C/G (Gln27Glu). In multivariable regression analyses, the beta2AR46 SNP was
      significantly associated with LV systolic dysfunction, with each minor allele
      additively decreasing the odds for LV ejection fraction <50%. The beta1AR1165 and
      beta2AR46 SNPs were associated with higher dopamine requirement during the donor
      management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI
      1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 MUg/kg/min of
      dopamine compared to those with the CC and GG genotypes. However, no significant
      associations were found between betaAR SNPs and cardiac dysfunction in 364 donors
      managed from 2007-2008, perhaps due to changes in donor management, lack of power
      in this validation cohort, or the absence of a true association. betaAR
      polymorphisms may be associated with cardiac dysfunction after brain death, but
      these relationships require further study in independent donor cohorts.

PMID- 22994656
TI  - Identification of the PAG1 gene as a novel target of inherent radioresistance in
      human laryngeal carcinoma cells.
AB  - Laryngeal carcinoma, as a malignant tumor that occurs in the head and neck
      region, is widely treated by radiation, but in some cases, the cancer is
      radioresistant to the radiotherapy. The reason for the radioresistant response
      needs to be clinically understood. We designed our present study to identify the
      molecules that may be involved in this radioresistant response. In this study, we
      initially established the inherent radioresistant (Hep-2max) and radiosensitive
      (Hep-2min) cell lines from the parental laryngeal cancer cell line Hep-2.
      Furthermore, using microarray analysis, we identified a novel inherent
      radioresistance-related gene, phosphoprotein associated with glycosphingolipid
      enriched microdomains1 (PAG1). We showed that siRNA directed against PAG1 in a
      radioresistant (Hep-2max) cell line dramatically enhanced the radiosensitivity
      and IR-induced cell death. On the contrary, ectopic expression of PAG1 in
      radiosensitive (Hep-2min) cell lines led to radioresistance and suppressed the IR
      induced cell death. Taken together, our results indicate that the PAG1 gene may
      be a novel, promising radiosensitization target for laryngeal carcinoma.

PMID- 22994655
TI  - Patterns and timing of sunlight exposure and risk of basal cell and squamous cell
      carcinomas of the skin--a case-control study.
AB  - BACKGROUND: Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and
      squamous (SCC) cell carcinomas, is the most common cancer in Caucasians.
      Ultraviolet radiation (UVR) exposure is the most important environmental risk
      factor for NMSC. However, the precise relationship between UVR and the risk of
      NMSC is complex, and the relationship may differ by skin cancer type. METHODS: A
      case-control study was conducted among Florida residents to investigate measures
      of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of
      sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases
      recruited from a university dermatology clinic and 316 controls with no history
      of skin or other cancers. RESULTS: A history of blistering sunburn (a measure of
      intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI =
      1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in
      the sun for >= 3 months for 10 years or longer (a measure of continuous sunlight
      exposure) was also associated with both BCC and SCC in our study population. With
      the exception of younger age at first blistering sunburn, measures of younger age
      at sunlight exposure tended to be associated with SCC, but not BCC risk.
      CONCLUSIONS: Results from the current study suggest that sunlight exposure is
      associated with both BCC and SCC risk regardless of the pattern in which the
      exposure was received (i.e. intermittent vs. continuous). The data also suggest
      that sunlight exposure at a younger age may be more important for SCC but not
      BCC, however additional studies are needed to further characterize sunlight
      exposure-response relationships in different types of NMSC.

PMID- 22994657
TI  - Factors affecting the psychological functioning of Australian adults with chronic
      pain.
AB  - The role of resilience, for adults facing ongoing adversity in the form of
      chronic medical conditions, has received little attention in the past. This
      research investigated the impact of resilience and coping strategies on the
      psychological functioning of 87 Australian adults with chronic pain, using a self
      report questionnaire. It included the McGill Pain Questionnaire, the Connor
      Davidson Resilience Scale, the Coping Strategies Questionnaire, the 36-item Short
      Form Health Survey, and the Depression, Anxiety and Stress Scale. Using
      hierarchical regression, after the effects of pain severity, catastrophizing, and
      ignoring the pain were controlled for, resilience was significantly associated
      with mental health-related quality of life (beta = 0.18, P < 0.05), depression
      (beta = -0.31, P < 0.01), and anxiety (beta = -0.20, P < 0.05). In the final
      model for depression, resilience had a stronger association than pain severity.
      Resilience did not, however, influence individual's perceptions of their physical
      health-related quality of life. The link between resilience and mental health
      related quality of life outcomes provides initial evidence for the potential
      application of resilience related interventions to pain management programs.

PMID- 22994658
TI  - Antioxidant activity of indole-based melatonin analogues in erythrocytes and
      their voltammetric characterization.
AB  - Melatonin (MLT) is a strong free-radical scavenger, which protects the body from
      the effects of oxidants. In recent years, MLT have been described resulting in
      much attention in the development of synthetic compounds possessing. As a part of
      our ongoing study a series of indole-based MLT analogue hydrazide/hydrazone
      derivatives were synthesized, characterized and in vitro antioxidant activity was
      investigated by evaluating their reducing effect against oxidation of a redox
      sensitive fluorescent probe. Membrane stabilizing effect of all compounds was
      also investigated by lactate dehydrogenase leakage assay. Furthermore
      voltammetric methods have been applied to the synthesized compounds to
      characterize oxidation potentials to get insight into their metabolism owing to
      the oxidation mechanisms taking place at the electrode and in the body share
      similar principles. 

PMID- 22994660
TI  - Contraindications for external cephalic version in breech position at term: a
      systematic review.
AB  - OBJECTIVE: External cephalic version (ECV) is a safe and effective intervention
      that can prevent breech delivery, thus reducing the need for cesarean delivery.
      It is recommended in national guidelines. These guidelines also mention
      contraindications for ECV, and thereby restrict the application of ECV. We
      assessed whether the formulation of these contraindications in guidelines are
      based on empiric data. DESIGN: Systematic review. POPULATION: Pregnant women with
      a singleton breech presentation from 34 weeks. METHODS: We searched the National
      Guideline Clearinghouse, the Cochrane Central Register of Controlled Trials,
      MEDLINE (1953-2009), EMBASE (1980-2009), TRIP database (until 2011), NHS
      (National Health Services, until 2011), Diseases database (until 2011) and NICE
      guidelines (until 2011) for existing guidelines on ECV and studied the
      reproducibility of the contraindications stated in the guidelines. Furthermore,
      we systematically reviewed the literature for contraindications and evidence on
      these contraindications. MAIN OUTCOME MEASURES: Contraindications of ECV.
      RESULTS: We found five guidelines mentioning 18 contraindications, varying from
      five to 13 per guideline. The contraindications were not reproducible between the
      guidelines with oligohydramnios as the only contraindication mentioned in all
      guidelines. The literature search yielded 60 studies reporting on 39 different
      contraindications, of which we could only assess evidence of six of them.
      CONCLUSION: The present study shows that there is no general consensus on the
      eligibility of patients for ECV. Therefore we propose to limit contraindications
      for ECV to clear empirical evidence or to those with a clear pathophysiological
      relevance.

PMID- 22994661
TI  - Caring for new mothers: diagnosis, management and treatment of nipple dermatitis
      in breastfeeding mothers.
AB  - Breastfeeding is thought to be the most optimal form of infant nutrition. Nursing
      mothers are generally advised to continue breastfeeding until the infant is two
      years of age or beyond. Unfortunately, however, a majority of nursing mothers
      will discontinue breastfeeding much earlier than recommended. The most common
      reason for early discontinuation of breastfeeding is nipple pain. It is,
      therefore, essential that dermatologists know how to appropriately diagnose and
      effectively treat nipple pain associated with nipple dermatitis among nursing
      mothers. This review article provides a detailed discussion on the clinical
      features and management of various causes of nipple dermatitis during lactation,
      including problems with infant latch-on, congenital oral anomalies, plugged
      lactiferous ducts, atopic dermatitis, irritant contact dermatitis, allergic
      contact dermatitis, yeast infections, bacterial infections, herpes simplex virus,
      and Raynaud's phenomenon of the nipple.

PMID- 22994659
TI  - Number of daily pills, dosing schedule, self-reported adherence and health status
      in 2010: a large cross-sectional study of HIV-infected patients on antiretroviral
      therapy.
AB  - OBJECTIVES: The aim of the study was to assess whether pill burden is associated
      with self-reported adherence to current combination antiretroviral regimens and
      health status in a large sample of unselected and chronically treated HIV
      infected patients. METHODS: An adherence and health status questionnaire was
      offered to all patients collecting their drugs between March and May 2010 at our
      clinic; both parameters were primarily evaluated using a visual analogue scale.
      Linear correlations were evaluated using Spearman's correlation coefficient.
      Wilcoxon's rank-sum test and the chi(2) test were used to compare quantitative
      and qualitative variables. The generalized linear model was used in multivariable
      analyses. RESULTS: Among 2763 subjects on treatment during the study period, 2114
      (78.8% male; mean age 46.9 +/- 8.84 years) were tested for adherence; 1803
      (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age,
      gender, HIV risk factor, current CD4 count, pill burden and dosing interval,
      adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and
      directly associated with current CD4 count (P = 0.029). After adjusting for the
      same variables, health status was better in patients with undetectable viraemia
      (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared
      with injecting drug users and those with other risk factors (P < 0.0001 for MSM
      and P = 0.008 for heterosexuals); it was also directly associated with current
      CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill
      burden (P = 0.019). CONCLUSIONS: In this highly adherent population, the number
      of daily pills was related to self-reported health status but not to self
      reported adherence, whereas the dosing interval did not influence self-reported
      adherence or health status.

PMID- 22994662
TI  - Acne in the adult female patient: a practical approach.
AB  - Acne vulgaris is a common reason why adult women present to dermatologists and
      can be a clinical challenge to treat. It may also be an important sign of an
      underlying endocrine disease such as Polycystic Ovary Syndrome (PCOS). Although
      standard acne therapies can be successfully used to treat acne in adult female
      patients, hormonal treatment is a safe and effective therapeutic option that may
      provide an opportunity to better target acne in this population, even when other
      systemic therapies have failed. In this article, a practical approach to the
      adult female patient with acne will be reviewed to enhance the dermatologist's
      ability to use hormonal acne therapies and to better identify and evaluate
      patients with acne in the setting of a possible endocrine disorder.

PMID- 22994663
TI  - Progressive cutaneous lesions in an elderly woman with systemic failure.

PMID- 22994664
TI  - A subungal lesion on the finger of a young woman.

PMID- 22994665
TI  - Melanoma in South-East Europe: epidemiological data from the central cancer
      registry and clinicopathological characteristics from the hospital-based registry
      in Serbia.
AB  - BACKGROUND: Melanoma in South-East Europe shows varying incidence from 1.7 per
      100,000 in Albania to 14.5 per 100,000 in Slovenia, but more detailed data from
      this region are scarce. In this study, we report epidemiological and
      clinicopathological characteristics of melanoma in central Serbia. MATERIALS AND
      METHODS: Epidemiological data were retrieved from the Cancer Registry of Central
      Serbia and clinicopathological data from the hospital-based registry. RESULTS:
      The ASR(W) incidence rate of melanoma was 4.2/100,000 (males) and 3.9/100,000
      (females), and ASR(W) mortality rates were 1.9/100,000 (males) and 1.4/100,000
      (females), with recorded rising trends in both of them. Data from the hospital
      based registry revealed a total of 266 patients treated from 2005 to 2010, with
      the median age at diagnosis of 57 (13-86) years. The most frequent
      histopathological subtype was superficial spreading melanoma (SSM; 63.53%), and
      ulceration was present in 40.6% of primary tumors. Median Breslow thickness was 3
      mm (0.1-25 mm). Primary tumors with thickness of more than 4 mm were found in
      31.95% of patients, and in this group statistically significant difference was
      found for younger age in patients with SSM (55 years vs. 61 years, P = 0.04).
      CONCLUSION: Low incidence rates in central Serbia and probably other countries of
      South-East Europe are accompanied by a large percentage of thick tumors and a
      significant proportion of younger patients with thick tumors. This points to the
      urgent need for more effective primary and secondary prevention of melanoma in
      these countries.

PMID- 22994666
TI  - Prevalence and treatment of palmoplantar keratoderma and tinea pedis in patients
      with Sezary syndrome.
AB  - BACKGROUND: Mycosis fungoides (MF) and the Sezary syndrome (SS) are non-Hodgkin's
      lymphomas that present with cutaneous lesions. Sezary syndrome is characterized
      by blood involvement, exfoliative eryrthroderma, lymphadenopathy, pruritus,
      keratoderma, and immunosuppression. This study was to estimate the prevalence of
      palmoplantar keratoderma and tinea pedis in Sezary syndrome and to analyze the
      effectiveness of anti-fungal treatment. METHODS: We conducted a retrospective
      review of 1562 prospectively collected patients at the MD Anderson Cancer Center
      Cutaneous Lymphoma Clinic over sixteen years. All patients' palms and soles were
      evaluated for clinical evidence of keratoderma (hyperkeratosis) and for
      dermatophytosis (tinea pedis or unguum) by examining scales under 10% potassium
      hydroxide by light microscopy for hyphae. RESULTS: Of 138 Sezary syndrome
      patients (88 men, 50 women, median age at diagnosis 64 years), 85 (61.6%) had
      palmoplantar keratoderma; 45 of the 85 Sezary syndrome patients (52.9%) also had
      coexisting tinea pedis. Only 14 (10.1%) had tinea pedis without keratoderma.
      Treatment for tinea pedis resulted in microscopy cure of keratoderma in 12 of 45
      (26.7%) patients and clinical improvement. CONCLUSIONS: The prevalence of
      palmoplantar keratoderma in Sezary syndrome is 61.6%, with co-existing tinea
      pedis found in 52.9%. Palmoplantar keratoderma with tinea pedis showed clinical
      improvement with fungicidal therapy suggesting that tinea often contributes to
      the pathogenesis and severity of Sezary syndrome-related keratoderma.

PMID- 22994667
TI  - Multiple cutaneous and uterine leiomyomatosis in a 36-year-old female, and
      discussion of hereditary leiomyomatosis and renal cell carcinoma.

PMID- 22994668
TI  - Cutaneous leishmaniasis: cryosurgery using carbon dioxide slush in a resource
      poor country.
AB  - Leishmaniasis is a widespread parasitic disease seen most often in children and
      young adults, although it may occur at any age. In Yemen, up until now, specific
      treatment for cutaneous leishmaniasis (CL) has been challenging. Available
      chemotherapy is expensive and replete with significant side effects. Standard
      cryosurgery with liquid nitrogen is prohibitively expensive and often
      unavailable. The objective of this paper is to highlight the importance of
      cryosurgery with carbon dioxide slush in the treatment of CL in an economically
      underdeveloped region as a cost-effective, simple, successful, and affordable
      option.

PMID- 22994670
TI  - Smashed skin grafting or smash grafting - a novel method of vitiligo surgery.
AB  - INTRODUCTION: Vitiligo is an acquired progressive disorder characterized by
      destruction of melanocytes in the lesion and the lesional hair follicles. A
      number of new therapeutic options for vitiligo have become available over the
      last decade or so both on the medical as well as surgical side. One among them is
      the smashed skin grafting or simply smash grafting, which is a modification of
      split-thickness grafting. In this method, the graft undergoes "smashing" before
      being applied to the recipient site. Though a simple and effective procedure,
      very few people are doing the procedure either due to lack of awareness or due to
      lack of published data. MATERIALS AND METHODS: Smash skin grafting was performed
      in 26 patients with vitiligo in Mahatma Gandhi Institute of Medical Sciences,
      Sewagram, Maharashtra, India. RESULTS: Smashed skin grafting helped to achieve
      more than 90% repigmentation of the vitiligo patches in our patients.
      CONCLUSIONS: Smashed skin grafting is a simple procedure with fewer side effects,
      better outcome, and high patient satisfaction or, in simple words, it can be
      considered as an alternative to various conventional surgical modalities like
      punch grafting and melanocyte cell culture methods. This article deals with the
      steps of the procedure, results of the surgery in a small group of patients, and
      the necessity of increasing the awareness of smash grafting.

PMID- 22994669
TI  - Adverse effects of intralesional meglumine antimoniate and its influence on
      clinical laboratory parameters in the treatment of cutaneous leishmaniasis.
AB  - OBJECTIVES: Intralesional injection of pentavalent antimoniate is recommended by
      the World Health Organization for the treatment of cutaneous leishmaniasis (CL).
      This study aimed to evaluate the adverse effects of intralesional injection of
      meglumine antimoniate (Glucantime((r)) ) and its influence on clinical laboratory
      parameters. METHODS: A total of 105 patients with suspected lesions and
      therapeutic features of CL diagnosed by direct smear or skin biopsy were included
      in this study. Intralesional injection of Glucantime((r)) was administered to
      treat CL. Fifty-five of the 105 patients were checked for hematological features,
      liver and kidney function, and fasting blood sugar levels before and after
      treatment. RESULTS: The observed side effects included pain (89.5%), burning
      sensation (81.9%), erythema (45.7%), pruritus (28.6%), secondary infection
      (17.1%), nausea (11.4%), vomiting (7.6%), urticaria (5.7%), necrosis (2.9%),
      sporotrichoid lesions (2.9%), dizziness (1.9%), dyspnea (1.9%), and anaphylactic
      shock (0.9%). No statistically significant differences were found in occurrences
      of adverse effects according to the part of the body affected, patient sex or age
      group, except for pruritus, which appeared more frequently in extremities than in
      other parts of the body (P < 0.001), and secondary infection, which was observed
      more frequently in people aged >45 years (P < 0.042). All clinical parameters
      remained normal after treatment. CONCLUSIONS: The occurrence of severe adverse
      reactions, particularly of anaphylactic shock, should be considered before
      treatment with Glucantime((r)) is initiated. Thus, it is important that
      intralesional Glucantime((r)) injections are administered in centers that are
      well equipped with appropriate resuscitation and support apparatus.

PMID- 22994671
TI  - Corticosteroid-induced hyperglycemia is increased 10-fold in patients with
      pemphigus.
AB  - This study aimed to highlight the importance of routine screening for
      hyperglycemia and to develop a standardized, evidence-based approach for the
      management of pemphigus patients on prolonged systemic corticosteroid (CS)
      therapy. A cross-sectional study was conducted in two university-affiliated
      teaching hospitals using a referred sample of 200 patients with a confirmed
      diagnosis of pemphigus vulgaris, pemphigus foliaceus, or mucous membrane
      pemphigoid. All patients were receiving systemic CS therapy. A total of 150
      patients responded to the survey. Six participants were excluded and 144 were
      included. The main outcome measure was blood glucose level to detect
      hyperglycemia. New-onset hyperglycemia was identified in 40% of patients who
      received CS therapy. None of the expected variables, including age, body mass
      index, family history of diabetes, corticosteroid dose, and duration of
      corticosteroid therapy, were independently associated with new-onset
      hyperglycemia. These findings indicate that the prevalence of CS-induced
      hyperglycemia in pemphigus patients is 40% and that in patients with pemphigus or
      MMP, CS therapy is associated with a markedly increased risk for hyperglycemia
      (odds ratio = 10.7, 95% confidence interval 1.38-83.50) compared with that of
      patients with the same diseases who do not receive CS therapy.

PMID- 22994672
TI  - Efficacy of intradermal radiofrequency combined with autologous platelet-rich
      plasma in striae distensae: a pilot study.
AB  - BACKGROUND: Different types of laser have recently been reported as effective
      tools of treatment in striae distensae. Although fractional photothermolysis is
      effective for striae distensae, post-inflammatory hyperpigmentation is a major
      concern and common complication. There are no reports of the effects of using an
      intradermal radiofrequency (RF) device in striae distensae. Autologous platelet
      rich plasma (PRP) is an effective treatment known for its wound-healing effects.
      METHODS: Nineteen Asian female patients with striae distensae were enrolled in
      this study. Three sessions of intradermal RF (1134-kHz frequency, 12-W power, 26
      G electrode size) combined with autologous PRP were performed in each patient at
      intervals of four weeks. Patients were evaluated subjectively by the
      investigators and by themselves. RESULTS: Evaluation of clinical results at four
      weeks after treatment showed that only one (5.3%) of the 19 patients achieved
      excellent improvement, whereas seven (36.8%) demonstrated marked improvement, six
      (31.6%) showed moderate improvement, and five (26.3%) showed mild improvement.
      None of the patients showed worsening of striae distensae. A total of 63.2% of
      patients reported they were "satisfied" or "very satisfied" with the degree of
      overall improvement. CONCLUSIONS:   Intradermal RF combined with autologous PRP
      appears to be an effective treatment for striae distensae.

PMID- 22994673
TI  - Learning to love dermatology by caring for the underserved: a field trip into the
      heart of Amazonia.

PMID- 22994674
TI  - Hypoxia-induced response of cell cycle and apoptosis regulators in melanoma.

PMID- 22994675
TI  - Subcutaneous phaeohyphomycosis in immunocompetent child caused by Exophiala
      jeanselmei.

PMID- 22994676
TI  - Eruptive disseminated Spitz nevi in a 26-year-old African-American woman.

PMID- 22994677
TI  - Rosacea with severe ophthalmic involvement and blindness - a rare occurrence.

PMID- 22994679
TI  - Peptide-functionalized gold nanorods increase liver injury in hepatitis.
AB  - Targeted nanomedicine holds enormous potential for advanced diagnostics and
      therapy. Although it is known that nanoparticles accumulate in liver in vivo, the
      impact of cell-targeting particles on the liver, especially in disease
      conditions, is largely obscure. We had previously demonstrated that peptide
      conjugated nanoparticles differentially impact macrophage activation in vitro. We
      thus comprehensively studied the distribution of gold nanorods (AuNR) in mice in
      vivo and assessed their hepatotoxicity and impact on systemic and hepatic immune
      cells in healthy animals and experimental liver disease models. Gold nanorods
      were stabilized with either cetyltrimethylammonium bromide or poly(ethylene
      glycol) and additional bioactive tripeptides RGD or GLF. Gold nanorods mostly
      accumulated in liver upon systemic injection in mice, as evidenced by inductively
      coupled plasma mass spectrometry from different organs and by non-invasive
      microcomputerized tomography whole-body imaging. In liver, AuNR were only found
      in macrophages by seedless deposition and electron microscopy. In healthy
      animals, AuNR did not cause significant hepatotoxicity as evidenced by
      biochemical and histological analyses, even at high AuNR doses. However, flow
      cytometry and gene expression studies revealed that AuNR polarized hepatic
      macrophages, even at low doses, dependent on the respective peptide sequence,
      toward M1 or M2 activation. While peptide-modified AuNR did not influence liver
      scarring, termed fibrosis, in chronic hepatic injury models, AuNR-induced
      preactivation of hepatic macrophages significantly exacerbated liver damage and
      disease activity in experimental immune-mediated hepatitis in mice. Bioactively
      targeted gold nanoparticles are thus potentially harmful in clinically relevant
      settings of liver injury, as they can aggravate hepatitis severity.

PMID- 22994680
TI  - An unusual presentation of gestational thrombocytopenia.
AB  - Thrombocytopenia is classically defined as a platelet count of less than 150
      000/ul. Counts from 100 000 to 150 000/ul are considered mildly depressed, 50 000
      to 100 000/ul moderately depressed, and less than 50 000/ul severely depressed.
      Thrombocytopenia occurs in about 10% of pregnant women. Gestational
      thrombocytopenia (GT) is a diagnosis of exclusion and considered the most
      prevalent cause of thrombocytopenia in pregnancy. GT accounts for almost 75% of
      cases of thrombocytopenia in pregnancy. The cause of GT is unclear, although
      existing studies denote the possibility of accelerated platelet consumption and
      the increased plasma volume during pregnancy. The presence of antiplatelet
      antibodies is not specific to GT. The degree of thrombocytopenia in GT is usually
      mild to moderate, usually remaining greater than 70 000/ul. Patients are
      asymptomatic with no evidence of bleeding and rarely preconception history of
      thrombocytopenia. The platelet count returns to normal within 2-12 weeks post
      partum. We wish to report a unique case of GT presenting as blurred vision due to
      retinal hemorrhages. 

PMID- 22994681
TI  - Pseudomonas syringae self-protection from tabtoxinine-beta-lactam by ligase TblF
      and acetylase Ttr.
AB  - Plant pathogenic Pseudomonas syringae produce the hydroxy-beta-lactam
      antimetabolite tabtoxinine-beta-lactam (TbetaL) as a time-dependent inactivating
      glutamine analogue of plant glutamine synthetases. The producing pseudomonads use
      multiple modes of self-protection, two of which are characterized in this study.
      The first is the dipeptide ligase TblF which converts tabtoxinine-beta-lactam to
      the TbetaL-Thr dipeptide known as tabtoxin. The dipeptide is not recognized by
      glutamine synthetase. This represents a Trojan Horse strategy: the dipeptide is
      secreted, taken up by dipeptide permeases in neighboring cells, and TbetaL is
      released by peptidase action. The second self-protection mode is elaboration by
      the acetyltransferase Ttr, which acetylates the alpha-amino group of the proximal
      inactivator TbetaL, but not the tabtoxin dipeptide.

PMID- 22994682
TI  - Efficacy of ascorbic acid, N-acetylcysteine, or combination of both on top of
      saline hydration versus saline hydration alone on prevention of contrast-Induced
      nephropathy: a prospective randomized study.
AB  - BACKGROUND: Antioxidant drugs such as N-acetylcysteine (NAC) and ascorbic acid
      have been evaluated in interventional studies to prevent contrast-induced
      nephropathy (CIN), however, there are limited data on comparing either or both,
      with background of standard intravenous saline hydration versus the standard
      intravenous saline hydration alone in preventing CIN. METHODS: We conducted a
      single-center randomized trial among patients undergoing coronary angiography or
      percutaneous coronary intervention who had serum creatinine >= 1.3 mg/dL or were
      on diabetes mellitus medication. Eligible patients were randomly assigned to one
      of the following 4 groups: (1) NAC, (2) ascorbic acid, (3) combination of both
      drugs, and (4) control group. Additionally, all the groups received the standard
      intravenous saline hydration. Creatinine was measured 4-5 days after procedure.
      RESULTS: A total of 243 patients were randomized; 62 to NAC, 57 to ascorbic acid,
      58 to both drugs, and 66 to placebo. The development of 0.5 mg/dL absolute
      increase of serum creatinine, 25% relative decrease of creatinine clearance, or
      either (CIN) were measured in the ascorbic acid group (3.6% for all), NAC group
      (6.8%, 3.4%, 8.5%, respectively), combined group (5.5%, 5.5%, 9.1%,
      respectively), and control group (6.2%, 6.2%, 7.7%, respectively). None of these
      differences were significant (P = 0.896 for serum creatinine, P = 0.863 for
      creatinine clearance, and P = 0.684 for CIN). CONCLUSIONS: In a cohort of
      patients at risk of developing CIN, we could not detect any significant benefit
      of the use of ascorbic acid, NAC, or a combination of both drugs over the
      standard hydration regimen in preventing CIN.

PMID- 22994683
TI  - Creating, documenting and sharing network models.
AB  - As computational neuroscience matures, many simulation environments are available
      that are useful for neuronal network modeling. However, methods for successfully
      documenting models for publication and for exchanging models and model components
      among these projects are still under development. Here we briefly review existing
      software and applications for network model creation, documentation and exchange.
      Then we discuss a few of the larger issues facing the field of computational
      neuroscience regarding network modeling and suggest solutions to some of these
      problems, concentrating in particular on standardized network model terminology,
      notation, and descriptions and explicit documentation of model scaling. We hope
      this will enable and encourage computational neuroscientists to share their
      models more systematically in the future.

PMID- 22994684
TI  - The changes of Th17 cells and the related cytokines in the progression of human
      colorectal cancers.
AB  - BACKGROUND: The role of Th17 cells in colorectal tumorigenesis and development
      still remains unclear, despite the fact that it has been established in the
      pathogenesis of autoimmune diseases. METHODS: We first analyzed Th17 cells and
      Treg cells using flow cytometry in the circulation of colorectal adenoma (CRA)
      and colorectal carcinoma (CRC) patients and healthy controls, and the frequency
      of Th17 cells in peripheral blood mononuclear cells (PBMCs) stimulated by anti
      CD3 plus anti-CD28 and treated by IL-1beta, IL-6, and TGF-beta in different
      concentrations. We then detected cytokines IL-1beta, IL-6, IL-17A, IL-21, IL-23
      or TGF-beta by ELISA in sera and supernatants from both normal and tumor tissues
      cultured ex vivo. RESULTS: It was found that the percentage of Th17 and Treg
      cells increased in the circulation of both CRA and CRC patients; the increase of
      Th17 cells in the circulation occurred in early stages, whereas the increase of
      Treg cells in the circulation and the increase of Th17 cells in tumor tissues
      occurred in advanced stages. The subsequent cytokine profiling showed that, along
      CRC progression, IL-1beta, IL-17A and IL-23 underwent a similar change, while IL
      6 in CRC exhibited an opposite change, with Th17 cells. In addition, high levels
      of TGF-beta and IL-17A were detected in tumor tissues rather than in normal
      mucosa. The in vitro experiment further demonstrated that IL-1beta, IL-6 or TGF
      beta modulated Th17 cell expansion in PBMC. CONCLUSIONS: Our study reveals a
      unique change of Th17 cells, which is regulated possibly by IL-1beta, IL-6 and
      TGF-beta in the progression of CRC.

PMID- 22994685
TI  - Two-module organization of the mandible in the yellow-necked mouse: a comparison
      between two different morphometric approaches.
AB  - Mandibles of yellow-necked mouse (Apodemus flavicollis) were used to explore
      modularity. We tested a biological hypothesis that two separate modules (alveolar
      region and ascending ramus) can be recognized within the mandible. As a second
      research goal, we compared two different morphometric procedures under the
      assumption that methodological approaches that use either geometric or
      traditional morphometric techniques should give similar results. Besides
      confirmation of the predicted hypothesis of modularity, the application of both
      approaches revealed that: (i) modularity was somewhat more evident when it was
      analysed on the asymmetric (fluctuating asymmetry, FA) than on the symmetric
      (individual variation) component of variation; (ii) there is correspondence in
      the patterns of individual variation and FA, which indicates that integration of
      mandibular traits among individuals is primarily due to direct developmental
      interactions; and (iii) allometry does not obscure the hypothesized modularity
      for individual variation or for FA. In addition, traditional morphometric method
      allowed us to check whether allometry influenced each module to the same extent
      and to conclude that the ascending ramus is more heavily influenced by general
      size than the alveolar region. In studies of modularity, differences in methods
      can lead to discrepancies in the results, and therefore, some caution is required
      when comparing findings from different investigations. The substantial agreement
      between our results provides evidence that, when considering two-module
      organization of the mouse mandible, direct comparison among studies that use the
      methods applied herein is, in great part, reliable.

PMID- 22994687
TI  - Survival of horses following strangulating large colon volvulus.
AB  - REASONS FOR PERFORMING STUDY: The pattern of long-term survival and specific
      factors associated with long-term survival have not previously been evaluated in
      horses with a strangulating large colon volvulus (LCV). OBJECTIVES: To provide
      data on the long-term survival of horses with LCV and to identify pre-, intra-
      and post operative variables associated with survival. METHODS: Clinical data and
      long-term follow-up information were obtained from 116 horses with a
      strangulating LCV (>=360 degrees ) undergoing general anaesthesia. Two
      multivariable Cox proportional hazards models for post operative survival time
      were developed: Model 1 included all horses and evaluated preoperative variables
      and Model 2 included horses that survived anaesthesia and evaluated pre-, intra-
      and post operative variables. RESULTS: The study population comprised 116 horses.
      Eighty-nine (76.7%) survived general anaesthesia. Of these, the percentage that
      survived until discharge, to one year and to 2 years was 70.7%, 48.3% and 33.7%,
      respectively. Median survival time for horses that survived general anaesthesia
      was 365 days. In Model 1 increased preoperative packed cell volume (PCV) was
      significantly associated with reduced post operative survival (hazard ratio [HR]
      1.08, 95% confidence interval [CI] 1.05-1.11). However, this effect changed over
      time. In Model 2 abnormal serosal colour intraoperatively (HR 3.61, 95% CI 1.55
      8.44), increased heart rate at 48 h post surgery (HR 1.04, 95% CI 1.02-1.06), and
      colic during post operative hospitalisation (HR 2.63, 95% CI 1.00-6.95), were all
      significantly associated with reduced post operative survival. CONCLUSIONS:
      Survival time in horses with a LCV was associated with preoperative PCV, serosal
      colour, heart rate at 48 h post operatively and colic during post operative
      hospitalisation. POTENTIAL RELEVANCE: This study provides evidence-based
      information on the long-term survival of horses with LCV and identifies
      parameters that may assist decision-making by clinicians and owners.

PMID- 22994686
TI  - Proteomic analysis of Clostridium thermocellum core metabolism: relative protein
      expression profiles and growth phase-dependent changes in protein expression.
AB  - BACKGROUND: Clostridium thermocellum produces H2 and ethanol, as well as CO2,
      acetate, formate, and lactate, directly from cellulosic biomass. It is therefore
      an attractive model for biofuel production via consolidated bioprocessing.
      Optimization of end-product yields and titres is crucial for making biofuel
      production economically feasible. Relative protein expression profiles may
      provide targets for metabolic engineering, while understanding changes in protein
      expression and metabolism in response to carbon limitation, pH, and growth phase
      may aid in reactor optimization. We performed shotgun 2D-HPLC-MS/MS on closed
      batch cellobiose-grown exponential phase C. thermocellum cell-free extracts to
      determine relative protein expression profiles of core metabolic proteins
      involved carbohydrate utilization, energy conservation, and end-product
      synthesis. iTRAQ (isobaric tag for relative and absolute quantitation) based
      protein quantitation was used to determine changes in core metabolic proteins in
      response to growth phase. RESULTS: Relative abundance profiles revealed
      differential levels of putative enzymes capable of catalyzing parallel pathways.
      The majority of proteins involved in pyruvate catabolism and end-product
      synthesis were detected with high abundance, with the exception of aldehyde
      dehydrogenase, ferredoxin-dependent Ech-type [NiFe]-hydrogenase, and RNF-type
      NADH:ferredoxin oxidoreductase. Using 4-plex 2D-HPLC-MS/MS, 24% of the 144 core
      metabolism proteins detected demonstrated moderate changes in expression during
      transition from exponential to stationary phase. Notably, proteins involved in
      pyruvate synthesis decreased in stationary phase, whereas proteins involved in
      glycogen metabolism, pyruvate catabolism, and end-product synthesis increased in
      stationary phase. Several proteins that may directly dictate end-product
      synthesis patterns, including pyruvate:ferredoxin oxidoreductases, alcohol
      dehydrogenases, and a putative bifurcating hydrogenase, demonstrated differential
      expression during transition from exponential to stationary phase. CONCLUSIONS:
      Relative expression profiles demonstrate which proteins are likely utilized in
      carbohydrate utilization and end-product synthesis and suggest that H2 synthesis
      occurs via bifurcating hydrogenases while ethanol synthesis is predominantly
      catalyzed by a bifunctional aldehyde/alcohol dehydrogenase. Differences in
      expression profiles of core metabolic proteins in response to growth phase may
      dictate carbon and electron flux towards energy storage compounds and end
      products. Combined knowledge of relative protein expression levels and their
      changes in response to physiological conditions may aid in targeted metabolic
      engineering strategies and optimization of fermentation conditions for
      improvement of biofuels production.

PMID- 22994688
TI  - Cystic fibrosis, elevated gamma-glutamyltransferase, and lung transplant outcome.

PMID- 22994689
TI  - Exploratory factor analysis and psychometric evaluation of the teacher reporting
      attitude scale for child sexual abuse.
AB  - This paper presents an evaluation of an instrument to measure teachers' attitudes
      toward reporting child sexual abuse and discusses the instrument's merit for
      research into reporting practice. Based on responses from 444 Australian
      teachers, the Teachers' Reporting Attitude Scale for Child Sexual Abuse was
      evaluated using exploratory factor analysis. The scale isolated three dimensions:
      commitment to the reporting role, confidence in the system's response to reports,
      and concerns about reporting. These three factors accounted for 37.5% of the
      variance in the 14-item measure. Alpha coefficients for the subscales were 0.769
      (commitment), 0.617 (confidence), and 0.661 (concerns). The findings provide
      insights into the complexity of studying teachers' attitudes toward reporting of
      child sexual abuse and have implications for future research.

PMID- 22994690
TI  - Utilizing online training for child sexual abuse prevention: benefits and
      limitations.
AB  - The prevalence of child sexual abuse demands innovative approaches to prevent
      further victimization. The online environment provides new opportunities to
      expand existing child sexual abuse prevention trainings that target adult
      gatekeepers and allow for large scale interventions that are fiscally viable.
      This article discusses the benefits and limitations of conducting online
      organizational trainings from the perspective of participants, including what
      participants found effective, what challenges were most commonly encountered, and
      trainee perspectives of the program's overall impact. The final section provides
      recommendations and lessons learned for practitioners and researchers who hope to
      utilize and assess online prevention trainings in the future.

PMID- 22994691
TI  - Evaluation of a sexual abuse prevention workshop in a multicultural, impoverished
      urban area.
AB  - Participants in the ESPACE sexual abuse prevention workshop were in grades 1
      through 4 and attended three Montreal, Canada, public schools in low
      socioeconomic areas. The sample was culturally diverse, with half born outside of
      Canada. An evaluation was conducted to explore the effects associated with
      participating in the workshop and the effects of booster sessions conducted two
      years later. Outcomes included knowledge gained, the ability to offer behavioral
      responses to abusive situations, peer victimization, sense of safety, empathy,
      self-efficacy, and support. Results revealed that participants in this sample
      obtained low scores on measures of sexual abuse knowledge and that short booster
      sessions that elicit children's recall of the learned material might produce
      greater improvements.

PMID- 22994692
TI  - Sexual abuse in a classroom of ten male students: a group victimization.
AB  - The term "professional perpetrator" is used to describe individuals who commit
      sexual abuse in the capacity of a position of trust such as a teacher, household
      member, or employer. There is an increasing body of evidence focusing on educator
      sexual abuse in the school environment. However, data are limited about this
      topic. The aim of this paper is to present the rare occurrence of the case of a
      male teacher in Turkey who sexually abused his students in an elementary school.
      Although it is unknown which populations are most vulnerable to sexual abuse, in
      Turkey we think that the indigenous population is at risk. Abuse cases are not
      logged into the criminal justice system because the majority of abuse allegations
      are ignored or disbelieved by families.

PMID- 22994693
TI  - Child sexual abuse in the Anglican Church of Australia.
AB  - This article reports on a retrospective study of cases of child sexual abuse
      complaints made against clergy, other employed pastoral staff, and volunteers in
      the Anglican Church of Australia between 1990 and 2008. There were 191
      allegations of sexual abuse made by 180 complainants against 135 individuals.
      Twenty-seven of those 135 had more than one complaint made against them. Three
      quarters of all complainants were male. The most likely explanation for the large
      proportion of abused males is that the church gives many more opportunities for
      abusers to be alone with boys than with girls. Prevention strategies need to
      focus on reducing the opportunities for abuse to occur as well strategies
      concerning the recruitment of professional staff and volunteers.

PMID- 22994694
TI  - Child sexual abuse and women's sexual health: the contribution of CSA severity
      and exposure to multiple forms of childhood victimization.
AB  - Research studies have provided increasing evidence for the potential adverse
      impact of child sexual abuse on women's sexual health. The present study examined
      the association between child sexual abuse and sexual health while controlling
      for various forms of childhood victimization. Self-report questionnaires were
      administered to 889 young women from the province of Quebec. Results suggest that
      child sexual abuse survivors were more likely to report having experienced other
      forms of childhood victimization than were women without child sexual abuse.
      Women with a history of both child sexual abuse and multiple forms of
      victimization were at greater risk of experiencing more adverse outcomes,
      including risky sexual behaviors, sexual problems, and negative sexual self
      concept. Regression analyses revealed that child sexual abuse was significantly
      related to indicators of sexual health outcomes even when controlling for the
      effect of single forms of victimization. Clinically, interventions optimizing
      sexual health may be particularly helpful for a subgroup of child sexual abuse
      survivors.

PMID- 22994695
TI  - Sexual revictimization in adult women: examining factors associated with their
      childhood and adulthood experiences.
AB  - Using data collected from a sample of adult women (n = 234), this study examined
      the relationship between the experience and disclosure of childhood sexual abuse
      and subsequent adult sexual violence. Multivariate analyses revealed that
      physical force during the childhood sexual abuse experience was significant in
      both children's decisions to disclose as well as in adult revictimization
      experiences. Furthermore, childhood disclosures were significantly associated
      with adulthood disclosures about revictimization, but only when there was no
      action following the childhood disclosure. The implications for enhancing
      training and education about understanding and responding to children and women's
      disclosures about sexual violence are discussed.

PMID- 22994696
TI  - Pediatric liver transplantation using reduced and hyper-reduced left lateral
      segment grafts: a 10-year single-center experience.
AB  - Few studies have examined the long-term outcomes and prognostic factors
      associated with pediatric living living-donor liver transplantation (LDLT) using
      reduced and hyper-reduced left lateral segment grafts. We conducted a
      retrospective, single-center assessment of the outcomes of this procedure, as
      well as clinical factors that influenced graft and patient survival. Between
      September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45
      kg) underwent LDLT using reduced (partial left lateral segment; n = 5,
      monosegment; n = 26), or hyper-reduced (reduced monosegment grafts; n = 18) left
      lateral segment grafts. In all cases, the estimated graft-to-recipient body
      weight ratio of the left lateral segment was more than 4%, as assessed by
      preoperative computed tomography volumetry, and therefore further reduction was
      required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal
      venous complications occurred in eight patients (16.3%). The overall patient
      survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%,
      respectively. Multivariate analysis revealed that recipient age of less than 2
      months and warm ischemic time of more than 40 min affected patient survival.
      Pediatric LDLT using reduced and hyper-reduced left lateral segment grafts
      appears to be a feasible option with acceptable graft survival and vascular
      complication rates.

PMID- 22994697
TI  - Relationship between levels of IFNgamma, TNFalpha, and TGFbeta and pruritus in
      sulfur mustard-exposed veterans.
AB  - One of the foremost negative effects of sulfur mustard (SM) is chronic pruritus,
      which affects the quality-of-life. In the present study, pruritus was assessed in
      relation with inflammatory factors in the blood. Seventy-two blood samples were
      collected from SM-injured veterans of the Iran-Iraq War (Case Group; n = 36) and
      non-exposed patients (Control Group; n = 36) suffering from skin pruritus.
      Pruritus severity in all subjects was assessed, as were levels of IFNgamma,
      TGFbeta, and TNFalpha. The results indicated that total pruritus severity did not
      significantly differ between the two groups. While WBC counts in Control patients
      were significantly higher than among the exposed veterans, there were no
      significant differences in levels of any specific WBC sub-classes. Levels of
      serum IFNgamma and TGFbeta in the control subjects were significantly greater
      than those in the exposed veterans. In contrast, serum TNFalpha in the SM-exposed
      group appeared to be in the normal range, albeit significantly higher than that
      of the control group. A positive correlation between pruritus and each of the
      evaluated cytokines was noted in the Case Group. As for the non-SM-exposed
      veterans, correlations were significant only in the cases of IFNgamma
      (stimulated) and TGFbeta. The results of the present study suggested that there
      might be a relationship between cytokine alterations and pruritus in SM-exposed
      veterans. Based on these studies, designing of new treatments to modulate blood
      levels of mediators might be helpful to decrease the problem of SM-induced
      pruritus, thereby improving the quality-of-life in exposed veterans.

PMID- 22994698
TI  - Qualitative study of humanization-based nursing education focused on role
      modeling by instructors.
AB  - This study explored the perspectives and experiences of Iranian nursing students
      and nursing instructors about role modeling. Using a purposeful sampling
      strategy, 22 nursing students and seven nursing instructors were recruited from
      five nursing schools in Tehran. Three focus-group discussions and two individual
      semi-structured interviews with nursing students, and seven semi-structured
      interviews with nursing instructors, were conducted to gather data. A qualitative
      content analysis approach was utilized and three main themes emerged during data
      analysis: "attempt to promote emotional development,""attempt to promote
      spiritual development," and "attempt to promote intellectual development." It was
      concluded that understanding the factors influencing role modeling will be
      helpful for developing strategies to integrate role modeling into nursing
      education so as to promote the quality of nursing education in Iran. 

PMID- 22994699
TI  - High on-treatment platelet reactivity on commonly prescribed antiplatelet agents
      following transient ischaemic attack or ischaemic stroke: results from the
      Trinity Antiplatelet Responsiveness (TRAP) study.
AB  - BACKGROUND AND PURPOSE: The prevalence of ex vivo 'high on-treatment platelet
      reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic
      cerebrovascular disease (CVD) is uncertain. METHODS: HTPR was assessed with PFA
      100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet
      activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed
      with whole-blood flow cytometry. Patients were assessed at baseline [<= 4 weeks
      of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and >=
      90 days after changing treatment from (i) no medication to aspirin monotherapy (N
      = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a
      novel, 'longitudinal fashion' as failure to prolong relevant closure times
      compared with the patient's 'baseline value' before he/she underwent an
      antiplatelet change by more than twice the coefficient of variation of the assay.
      RESULTS: (i) C-EPI closure times increased at 14 days and 90 days after
      commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated
      HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but
      not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14
      days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation
      was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet
      complexes decreased at 14 days (P = 0.02), but this reduction was not maintained
      90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent
      vascular event during prospective follow-up. CONCLUSIONS: Longitudinal
      definitions of HTPR in patients with ischaemic CVD who are undergoing a change in
      antiplatelet therapy have the potential to provide more clinically meaningful
      information than traditional 'cross-sectional definitions' of HTPR which are
      usually based on the comparison of patients' values with those in healthy
      controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be
      used to monitor ex vivo responsiveness to aspirin, and larger, prospective
      studies are warranted to assess the clinical predictive value of this and other
      platelet function tests in patients with ischaemic CVD.

PMID- 22994700
TI  - The use of boundary objects to enhance interprofessional collaboration:
      integrating complementary medicine in a hospital setting.
AB  - Because of the inherent complexity of human health, the provision of good quality
      patient care requires collaboration in multidisciplinary teams. Integrative
      healthcare provides a unique setting for the study of interprofessional
      collaboration in the context of power disparities. The research objective was to
      examine which means and mechanisms were used to facilitate interprofessional
      collaboration when integrating complementary medicine (CM) into a hospital's
      surgical department. Throughout 2010 we conducted a qualitative study in an
      Israeli public hospital's surgical department, using observations and 30 in-depth
      interviews with managers, surgeons, physicians, nurses, patients and CM
      practitioners. The sociological concepts of boundary actor and boundary object
      and the context of power relations served as a framework for this research. This
      article contributes to the field of interprofessional collaborative care research
      by: analysing types of collaboration inhibitors--epistemological and social
      structural gaps; pointing to boundary actors who establish interprofessional
      collaboration in an integrative hospital setting and noting the boundary objects
      they use; and comparing collaboration levels. The collaboration between CM
      practitioners and the department's staff is a loosely coupled system. When
      coordination was achieved, reaching profound agreements seemed of lesser
      importance to the parties. Closer collaboration and cross-fertilisation were
      found among CM practitioners.

PMID- 22994701
TI  - Inhibition of extracellular lipase from Streptomyces rimosus with 3,4
      dichloroisocoumarin.
AB  - Kinetic characterization of lipase inhibition was performed by activity
      measurement and mass spectrometry (MS), for the first time with serine-protease
      inhibitor 3,4-dichloroisocoumarin (DCI). Inhibition of Streptomyces rimosus
      extracellular lipase (SrLip), a member of the SGNH superfamily, by means of DCI
      follows the mechanism of two-step irreversible inhibition. The dissociation
      constant of the noncovalent E*I complex and first-order rate constant for
      inactivation were determined by incubation (Ki* = 26.6 +/- 2.8 uM, k2 = 12.2 +/-
      0.6 min-1) or progress curve (Ki* = 6.5 +/- 1.5 uM, k2 = 0.11 +/- 0.01 min-1)
      method. Half-times of reactivation for lipase inhibited with 10-fold molar excess
      of DCI were determined by activity measurement (t1/2 = 11.3 +/- 0.2 h), matrix
      assisted laser desorption/ionization (MALDI, t1/2 = 13.5 +/- 0.4 h), and electro
      spray ionization (ESI, t1/2 = 12.2 +/- 0.5 h) MS. The active SrLip concentration
      was determined by incubating the enzyme with near equimolar concentrations of
      DCI, followed by activity and MS measurement.

PMID- 22994702
TI  - Design, synthesis, structure-activity relationships, and docking studies of 1
      (gamma-1,2,3-triazol substituted prolyl)-(S)-3,3-difluoropyrrolidines as a novel
      series of potent and selective dipeptidyl peptidase-4 inhibitors.
AB  - Dipeptidyl peptidase-4 inhibitors hold great potential for the treatment of type
      2 diabetes. A series of 1-(gamma-1,2,3-triazol substituted prolyl)-(S)-3,3
      difluoropyrrolidines were designed, synthesized, and evaluated as novel
      dipeptidyl peptidase-4 inhibitors. Most of the compounds exhibited good in vitro
      potency against dipeptidyl peptidase-4. Among these, compounds 7j, 7q, and 7s
      displayed good dipeptidyl peptidase-4 activity and excellent selectivity versus
      other proteases including dipeptidyl peptidase-8, dipeptidyl peptidase-9, and
      FAP. The possible binding modes of compounds 7j, 7q, and 7s with dipeptidyl
      peptidase-4 were also explored by molecular docking simulation.

PMID- 22994703
TI  - Chronic lymphocytic leukemia and prognostic factors.
AB  - BACKGROUND: The clinical course of individual chronic lymphocytic leukemia (CLL)
      is highly variable and clinical staging systems do not help us to predict if and
      at what rate there will be disease progression in an individual patient diagnosed
      with early stage disease. Recently, several important observations related to
      other prognostic factors including lymphocyte doubling time (LDT), beta2
      microglobulin (beta2-MG), and percent of smudge cell in peripheral blood smears,
      cytogenetic and molecular analysis have been made. The aim of this study was to
      evaluate a range of prognostic factors in our CLL patients. DESIGN AND METHODS:
      Seventy patients with CLL were enrolled. Prognostic factors of disease including
      Binet staging, LDT, beta2-MG, ESR, LDH, percent of smudge cell in peripheral
      blood smear, absolute lymphocyte count, and conventional cytogenetic (CC)
      analysis were evaluated at diagnosis, and the patients were followed up to
      determine their outcome. We compared factors with each other and with Binet
      staging and prognosis. RESULTS: Enrolled patients aged 37-85 years at diagnosis
      or during follow up. There was no relationship between serum LDH level (P=0.3),
      ESR (P=0.11), percent of smudge cells in peripheral blood smear (P=0.94), and
      absolute lymphocyte count (P=0.18) with the stage of disease and prognosis, but
      the beta2 macroglobulin level (p<0.0001), LDT (p<0.001) had direct and
      significant relation with staging and outcome. In 19% of patients cytogenetic
      alteration were seen. CONCLUSION: The detection of cytogenetic alteration only
      using the CC method is not sufficient and we need to use FISH, but because FISH
      study is an expensive method not available in all areas, we believe that beta2 MG
      can be applied in its place as a good prognostic factor for CLL at diagnosis and
      during follow up. We suggest to add it to Binet staging for prognostic
      subgrouping of CLL.

PMID- 22994704
TI  - Bidirectional regulation of manganese superoxide dismutase (MnSOD) on the
      radiosensitivity of esophageal cancer cells.
AB  - The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may
      represent a new type of tumor suppressor protein. Overexpression of the cDNA of
      this gene by plasmid or recombinant lentiviral transfection in various types of
      cancer leads to growth suppression both in vitro and in vivo. We previously
      determined that changes in MnSOD expression had bidirectional effects on
      adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free
      radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO
      would also have a bidirectional effect on cellular radiosensitivity. To examine
      this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably
      transfected using lipofectamine with a pLenti6-DEST plasmid containing human
      MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert.
      Blastidicin-resistant colonies were isolated, grown, and maintained in culture.
      We found that moderate overexpression of MnSOD decreased growth rates, plating
      efficiency, and increased apoptosis. However, high overexpression increased
      growth rates, plating efficiency, and decreased apoptosis. When combined with NO,
      moderate overexpression of MnSOD increased the radiosensitivity of esophageal
      cancer cells, whereas high MnSOD overexpression had the opposite effect. This
      finding suggests a potential new method to kill certain radioresistant tumors and
      to provide radioresistance to normal cells.

PMID- 22994705
TI  - Serum levels of alpha-tocopherol, vitamin C, beta-carotene, and retinol in
      malignant pleural mesothelioma.
AB  - The aim of this study was to investigate the possible relationship between
      antioxidant vitamin levels and malignant pleural mesothelioma (MPM). For this
      purpose, we measured the serum levels of 4 antioxidant vitamins, beta-carotene,
      alpha-tocopherol, retinol, and ascorbic acid, in patients with environmentally
      induced MPM and in healthy controls from one tremolite village (Kureysler), the
      biggest erionite village (Tuzkoy) and Ankara. A total of 160 subjects were
      enrolled in the study, 42 (26.3%) diagnosed with MPM and 118 (73.7%) healthy
      subjects. A comparison was made between the MPM group and three control groups of
      which two were exposed and one was unexposed to mineral fibers. The study
      population consisted of 82 males (51%) and 78 females (49%) with a mean of age of
      44.8+/-14 years (range; 20-65 years). Lowest levels of beta-carotene, ascorbic
      acid, and alpha-tocopherol were found in MPM patients (MPM vs control groups
      combined, p<0.0001 for each antioxidant vitamin), without any relation to age or
      sex. There was no significant difference between the antioxidant levels of
      healthy controls of Tuzkoy and Ankara. In conclusion; our findings suggested an
      increased risk of MPM being associated with low levels of alpha-tocopherol and
      ascorbic acid in patients with MPM.

PMID- 22994706
TI  - Critical evaluation of fine needle aspiration cytology as a diagnostic technique
      in bone tumors and tumor-like lesions.
AB  - BACKGROUND: Though open surgical biopsy is the procedure of choice for the
      diagnosis of bone tumors, many disadvantages are associated with this approach.
      The present study was undertaken to evaluate the role of fine needle aspiration
      cytology (FNAC) as a diagnostic tool in cases of bony tumors and tumor-like
      lesions which may be conducted in centers where facilities for surgical biopsies
      are inadequate. METHODS: The study population consisted of 51 cases presenting
      with a skeletal mass. After clinical evaluation, radiological correlation was
      done to assess the nature and extent of each lesion. Fine needle aspiration was
      performed aseptically and smears were prepared. Patients subsequently underwent
      open surgical biopsy and tissue samples were obtained for histopathological
      examination. Standard statistical methods were applied for analysis of data.
      RESULTS: Adequate material was not obtained even after repeated aspiration in
      seven cases, six of which were benign. Among the remaining 44 cases, diagnosis of
      malignancy was correctly provided in 28 (93.3%) out of 30 cases and categorical
      diagnosis in 20 (66.67%). Interpretation of cytology was more difficult in cases
      of benign and tumor-like lesions, with a categorical opinion only possible in
      seven (50%) cases. Statistical analysis showed FNAC with malignant tumors to have
      high sensitivity (93.3%), specificity (92.9%) and positive predictive value of
      96.6%, whereas the negative predictive value was 86.7%. CONCLUSION: FNAC should
      be included in the diagnostic workup of a skeletal tumor because of its
      simplicity and reliability. However, a definitive pathologic diagnosis heavily
      depends on compatible clinical and radiologic features which can only be
      accomplished by teamwork. The cytological technique applied in this study could
      detect many bone tumors and tumor-like conditions and appears particularly
      suitable as a diagnostic technique for rural regions of India as other developing
      countries.

PMID- 22994707
TI  - Evaluation of BCL-6, CD10, CD138 and MUM-1 expression in diffuse large B-cell
      lymphoma patients: CD138 is a marker of poor prognosis.
AB  - The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors
      with uneven survival outcomes--germinal center B-cell (GCB) and non-germinal
      center B-cell (non-GCB). In the present study, we investigated the expression of
      GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort
      to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46
      Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry
      to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition,
      survival curves were calculated with reference to marker expression, age, sex and
      nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown
      in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being
      associated with better overall survival (p = 0.02), whereas positive CD138 was
      linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1
      had no impact on the overall survival. Among the clinical characteristics
      studied, diagnosis at an early age, nodal involvement and maleness were
      associated with a higher overall survival for DLBCL patients. Our results
      underline the importance of BCL-6 as a marker of better prognosis and CD138 as a
      marker of poor prognosis for DLBCL patients.

PMID- 22994708
TI  - Lack of influence of MGMT codon Leu84Phe and codon Ileu143Val polymorphisms on
      esophageal cancer risk in the Kashmir Valley.
AB  - The enzyme encoded by the MGMT gene is involved in the repair of alkylated
      lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed
      by the Kashmiri population contain high concentrations of these agents, it is
      biologically plausible that MGMT polymorphic variants may be associated with
      their risk of esophageal cancer. The present study was performed to assess
      whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT
      gene, close to the active site of the protein, might be linked to predisposition
      of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain
      reaction-restriction fragment length polymorphism on 92 cases and 77 healthy
      controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with
      any increase in risk. While the frequency of the Phe allele at codon 84 in cases
      was (0.16), slightly higher than controls (0.12), the difference was not
      statistically significant. Similarly, the frequency of Valine allele in cases at
      codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant
      association of MGMT genotypes with the clinicopatholgic variables of esophageal
      cancer patients was observed. In conclusion, MGMT variants at codon 84 and
      codon143 may not be involved in the susceptibility of the Kashmiri population to
      esophageal cancer.

PMID- 22994709
TI  - Linear and conformational B cell epitope prediction of the HER 2 ECD-subdomain
      III by in silico methods.
AB  - Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal
      growth factor receptor family of receptor tyrosine kinases that play important
      roles in all processes of cell development. Their overexpression is related to
      many cancers, including examples in the breast, ovaries and stomach. Anticancer
      therapies targeting the HER2 receptor have shown promise, and monoclonal
      antibodies against subdomains II and IV of the HER2 extra-cellular domain (ECD),
      Pertuzumab and Herceptin, are currently used in treatments for some types of
      breast cancers. Since anti HER2 antibodies targeting distinct epitopes have
      different biological effects on cancer cells; in this research linear and
      conformational B cell epitopes of HER2 ECD, subdomain III, were identified by
      bioinformatics analyses using a combination of linear B cell epitope prediction
      web servers such as ABCpred, BCPREDs, Bepired, Bcepred and Elliprro. Then,
      Discotope, CBtope and SUPERFICIAL software tools were employed for conformational
      B cell epitope prediction. In contrast to previously reported epitopes of HER2
      ECD we predicted conformational B cell epitopes P1C: 378-393 (PESFDGDPASNTAPLQ)
      and P2C: 500-510 (PEDECVGEGLA) by the integrated strategy and and P4: PESFDGD-X
      TAPLQ; P5: PESFDGDP X TAPLQ; P6: ESFDGDP X NTAPLQP; P7: PESFDGDP-X-NTAPLQ; P8:
      ESFDG-XX-TAPLQPEQL and P9: ESFDGDP- X-NTAPLQP by SUPERFICIAL software. These
      epitopes could be further used as peptide antigens to actively immune mice for
      development of new monoclonal antibodies and peptide cancer vaccines that target
      different epitopes or structural domains of HER2 ECD.

PMID- 22994710
TI  - Epidemiological trends of cancer morbidity at a government medical college
      hospital, Chandigarh, India.
AB  - AIM: An epidemiological shift has resulted in increase in the prevalence of non
      communicable diseases (NCD). Unlike other NCDs which are easily and definitely
      preventable, the knowledge of cancer prevention is still limited at present.
      Various aetiological factors are difficult to control since those are habit
      forming. Hence an available remedy remains its secondary and tertiary prevention
      for which appropriate planning is of paramount importance. Evidence based
      planning requires careful analysis of data with a view to prioritize various
      cancers. Keeping in view the fact that the adaptation of smoking free status in
      Chandigarh city might have a far reaching positive effect on the cancer related
      morbidity of the people, the following study was undertaken to provide base line
      data to be used for future comparisons. METHODS: The registers maintained in the
      Department of Radiotherapy were checked and those belonging to the years 1999 to
      2009 were utilized to analyze the cancer morbidity in respect to age, sex, and
      year of presentation to health care facility. RESULTS: A total of 4,600 cancer
      patients (males=2276, females=2324) demonstrated a gradual increase in the number
      of cancer cases from 150 in the year 1999 to 783 in the year 2009. The most
      common cancers amongst males were cancer of gastro-intestinal tract (GIT) and
      lung (including larynx) constituting 37.3% and 27.1% of the total, respectively.
      In females these were cancers of breast and cervix representing 33.3% and 17.6%
      of total cancer cases, respectively, and lung cancer constituted 5.3%. The
      maximum cases of bone cancer (53.8% of all bone cancers) were observed amongst
      children aged less than 20 years and lung cancer (48.2% of all lung cancers)
      among the elderly aged 60-69 years.

PMID- 22994711
TI  - Antioxidant activity of essential oils from Wedelia chinensis (Osbeck) in vitro
      and in vivo lung cancer bearing C57BL/6 mice.
AB  - AIM: The present investigation was to evaluate the effects of essential oils of
      Wedelia chinensis (Osbeck) on free radicals and in vivo antioxidant properties.
      METHODS: Essential oils were extracted using hydro-distillation and compound
      analysis was performed by GC-MS analysis. Screening for inhibitory activity was
      conducted by DPPH and OH-scavenging assays. In addition an in vivo study was
      carried out in cell line implanted cancer bearing mice with assessment of levels
      of catalase, superoxide dismutase, glutathione peroxidase, lipid peroxidation,
      nitric oxide and reduced glutathione. Finally, lungs were dissected out for
      histopathology study of metastasis. RESULTS: GC-MS analysis revealed the presence
      of carvocrol and trans-caryophyllene as the major compounds with 96% comparison
      with the Wilily and NBS libraries. The essential oil exhibited significant
      inhibition in DPPH free radical formation. Whereas reducing power and hydroxyl
      radical scavenging activity are dose dependent. When compared with the standard,
      it was found that the essential oil has more or less equal activity in scavenging
      free radicals produced. In the animal studies, the level of antioxidant enzymes
      catalase, superoxide dismutase and glutathione peroxidase, as well as
      glutathione, were found to be increased in treated groups whereas lipid
      peroxidation and nitric oxide were reduced. Histopathology report also shows that
      the essential oil has a significant combating effect against cancer development.
      CONCLUSION: In all the in vitro assays, a significant correlation existed between
      the concentrations of the essential oil and percentage inhibition of free
      radicals. The in vivo studies also has shown a very good antioxidant property for
      the essential oil during cancer development. From, these results the essential
      oil can be recommended for treating disease related to free radicals and to
      prevent cancer development.

PMID- 22994712
TI  - Induction of intrinsic and extrinsic apoptosis pathways in the human leukemic
      MOLT-4 cell line by terpinen-4-ol.
AB  - Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum
      (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of
      cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT
      4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with
      characteristic morphological features of apoptosis by Wright's staining. The mode
      of cell death was confirmed to be apoptosis by flow cytometric analysis after
      staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA
      histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell
      apoptosis mediated through an intrinsic pathway involving the loss of
      mitochondrial transmembrane potential (MTP) and release of cytochrome c into the
      cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic
      pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid.
      Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial
      pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase
      3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic
      MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.

PMID- 22994713
TI  - Comparison of diets of urban American Indian and non-Hispanic whites: populations
      with a disparity for biliary tract cancer rates.
AB  - AIM: The incidnece of biliary tract cancer (BTC) is many-fold higher for American
      Indians (AI) relative to non-Hispanic whites (NHW). Neither gallstones nor
      genetics can account for this difference. There is speculation that certain fatty
      acids in bile may play a role in preventing BTC. Since diet may influence
      composition of bile, we compared the dietary intakes of urban AI and NHW adult
      women in New Mexico. METHODS: Design, a cross- sectional study of the diets of
      lactating AI and NHW women was conducted. Setting, the University of New Mexico
      Hospital. Participants, healthy lactating women 18 to 39 years of age were
      recruited. Main outcome measures, a three-day diet record for each participant
      was analyzed. RESULTS: The AI women consumed less calcium (p = 0.04) and
      significantly less short and intermediate chain-length fatty acids (C4-C12), but
      nearly twice as much proinflammatory arachidonic acid as the NHWs (p < 0.01). The
      intake of dairy products by AI women was less than NHW women (p = 0.01) while the
      intake of processed meat products was higher (p < 0.01). CONCLUSION: Dietary
      factors may account for the difference in the risk of BTC between AI and NHW
      women.

PMID- 22994714
TI  - Expression of pituitary tumor transforming gene 1 is an independent factor of
      poor prognosis in localized or locally advanced prostate cancer cases receiving
      hormone therapy.
AB  - We investigated the prognostic value of pituitary tumor transforming gene 1
      (PTTG1) expression according to clinicopathological features among localized or
      locally advanced prostate cancer cases receiving hormone therapy. A retrospective
      study involved 64 patients receiving combined androgen blockade treatment was
      performed. PTTG1 expression was determined by immunohistochemical staining using
      initial needle biopsy specimens for diagnosis. Associations of PTTG1 with various
      clinicopathological features and disease-free survival were examined via uni- and
      multivariate analyses. No association between PTTG1 expression and clinical T
      stage, Gleason score, pretreatment PSA levels, risk groups was found (p=0.682,
      0.184, 0.487, 0.571, respectively). Univariate analysis revealed that increased
      PTTG1 expression, T3 stage and high risk group were associated with increased
      risk of disease progression (p=0.000, 0.042, and 0.001), and high PSA level had a
      tendency to predict disease progression (p=0.056). Cox hazard ratio analysis
      showed that PTTG1 low expression (p=0.002), PTTG1 high expression (p=0.000) and
      high risk group (p=0.0147) were significantly related to decreased disease-free
      survival. In conclusion, PTTG1 expression determined by immunohistochemical
      staining in needle biopsy specimens for diagnosis is a negative prognostic factor
      for progression in localized or locally advanced prostate cancer receiving
      hormone therapy.

PMID- 22994715
TI  - Prognostic value of vascular endothelial growth factor expression in resected
      gastric cancer.
AB  - BACKGROUND AND AIMS: Vascular endothelial growth factor (VEGF) is a potential
      prognostic biomarker for patients with resected gastric cancer. However, its role
      remains controversial. The objective of this study was to conduct a systematic
      review and meta-analysis of published literature. METHODS: Relevant literature
      was identified using Medline and survival data from published studies were
      collected following a methodological assessment. Quality assessment of eligible
      studies and meta-analysis of hazard ratio (HR) were performed to review the
      correlation of VEGF overexpression with survival and recurrence in patients with
      gastric cancer. RESULTS: Our meta-analysis included 44 published studies with
      4,794 resected patients. VEGF subtype for the prediction of overall survival (OS)
      included tissue VEGF (HR=2.13, 95% CI 1.71-2.65), circulating VEGF (HR=4.22, 95%
      CI 2.47-7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58-3.09), tissue VEGF-D (HR=1.73,
      95% CI 1.25-2.40). Subgroup analysis showed that HRs of tissue VEGF for OS were,
      1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) in non-Asians and Asians,
      respectively. The meta-analysis was also conducted for disease free survival
      (DFS) and disease specific survival (DSS). CONCLUSION: Positive expression of
      tissue VEGF, circulating VEGF, VEGF-C and VEGF-D were all associated with poor
      prognosis in resected gastric cancer. However, VEGF demonstrated no significant
      prognostic value for non-Asian populations. Circulating VEGF may be better than
      tissue VEGF in predicting prognosis.

PMID- 22994716
TI  - Health-related quality of life after treatment for malignant bone tumors: a
      follow-up study in China.
AB  - AIM: We conducted the present study to assess health-related quality of life
      (HRQoL) among bone cancer patients after surgical treatment in one large teaching
      hospitals in China, and assess the risk factors for improving the physical or
      mental HRQoL. METHODS: 344 eligible adult patients who were admitted to the
      hospital with malignant bone tumors during the period of Jun. 2008 to Dec. 2011,
      and a reference group with 361 health cases was recruited in the same hospital
      during the same period. All 344 patients were followed up for one year. The HRQoL
      before treatment and after one year was evaluated with the Medical Outcome Short
      Form 36 (SF-36). RESULTS: All 8 domains of HRQoL had the lowest scores greatly
      improved over the first year after discharge. However, the patients still had
      significantly lower scores in every domain than the reference group one year
      after discharge. Age and type of surgery were associated with HRQoL in the mental
      domain. CONCLUSION: The HRQoL of patients with malignant bone tumors greatly
      improved one year after the treatment. This study also highlighted the utility of
      HRQoL assessment for prognostic evaluation of patients after surgical treatment
      for bone cancer.

PMID- 22994717
TI  - LY294002 induces G0/G1 cell cycle arrest and apoptosis of cancer stem-like cells
      from human osteosarcoma via down-regulation of PI3K activity.
AB  - Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has
      bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a
      critical role in tumorigenesis and drug-resistance. It is known that
      phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell
      fates, such as proliferation, cell cycling, survival and apoptosis. Whether and
      how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still
      unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the
      cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented
      phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K
      phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis
      in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction
      by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which
      are involved in the mitochondrial apoptosis pathway. Therefore, our results
      indicate PI3K inhibitors may represent a potential strategy for managing human
      osteosarcoma via affecting CSCs.

PMID- 22994718
TI  - No association between the GSTM1 null genotype and risk of renal cell carcinoma:
      a meta-analysis.
AB  - BACKGROUND: Many studies have focused on possible associations between the
      glutathione S-transferase M 1 (GSTM1) null genotype and risk of renal cell
      carcinoma (RCC), but the impact remains unclear owing to obvious inconsistencies
      among the findings. The present study aimed to quantify the strength of any
      association in a meta-analysis. METHODS: We searched the PubMed, Embase and CBM
      databases for studies concerning the association between the GSTM1 null genotype
      and risk of RCC. We estimated the summary odds ratio (OR) with its 95% confidence
      intervals (95% CI) to assess the association. RESULTS: The meta-analysis showed
      the GSTM1 null genotype was not associated with risk of RCC overall (OR = 1.04,
      95% CI 0.92-1.18, P = 0.501). For Caucasians, the GSTM1 null genotype was also
      not associated with risk of RCC (OR = 1.02, 95% CI 0.90-1.16, P = 0.761). The
      cumulative meta-analyses showed a trend of no obvious association between GSTM1
      null genotype and risk of RCC as information accumulated. Sensitivity analyses by
      omitting those studies also did not materially alter the overall combined ORs. No
      evidence of publication bias was observed. CONCLUSION: Meta-analyses of available
      data show that the GSTM1 null genotype is not significantly associated with risk
      of renal cell carcinoma.

PMID- 22994719
TI  - Some epidemiological measures of cancer in Kuwait: national cancer registry data
      from 2000-2009.
AB  - INTRODUCTION: Cancer is the second cause of death in Kuwaiti people after
      cardiovascular diseases. This study is the first in the country to describe
      epidemiological measures related to cancer in this population. METHODS: Data
      obtained from the Kuwait cancer registry included all Kuwaiti patients between
      years 2000-2009. Analyses were conducted using age-specific rates, the age
      standardization-direct method, 95% confidence intervals (95% CI), cumulative risk
      by the age of 74 years, limited-duration prevalence, mortality and forecasting to
      year 2029. RESULTS: It was noted that the commonest cancer sites were colorectal
      with an age standardized incidence rate (ASIR) of 16.1/100,000 in males and
      breast (49.4/100,000) in the female population. The trend of cancer incidence
      (1974-2009) showed no statistically significant change. First causes of death due
      to cancer were female breast 8(6.4-9.6)/100,000 and lung (males) 8.1/100,000 (6.6
      10.0). The risk of developing cancer by the age of 74 was 13.4% (1/8) and 14.3%
      (1/7) in males and females respectively, and the risk of dying from cancer in the
      same age group was 1/17 and 1/23. By the end of 2009, prevalent cases represented
      0.52% of the Kuwaiti population. In the year 2029, the total number of cancer
      cases is expected to reach 1200 cases compared to 889 cases in 2009. CONCLUSIONS
      AND RECOMMENDATIONS: The most common cancers in Kuwait (breast, colorectal and
      lung) are largely preventable. Prompt and effective interventional prevention
      programs that vigorously involve diet, anti-smoking and physical activity for
      both sexes are urgently required.

PMID- 22994720
TI  - Predictive role of computer simulation in assessing signaling pathways of
      crizotinib-treated A549 lung cancer cells.
AB  - Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide.
      Crizotinib has been approved by the U.S. Food and Drug Administration for the
      treatment of patients with advanced NSCLC. However, understanding of mechanisms
      of action is still limited. In our studies, we confirmed crizotinib-induced
      apoptosis in A549 lung cancer cells. In order to assess mechanisms, small
      molecular docking technology was used as a preliminary simulation of signaling
      pathways. Interesting, our results of experiments were consistent with the
      results of computer simulation. This indicates that small molecular docking
      technology should find wide use for its reliability and convenience.

PMID- 22994721
TI  - Association between green tea and colorectal cancer risk: a meta-analysis of 13
      case-control studies.
AB  - OBJECTIVE: Experimental studies have suggested green tea to be a chemopreventive
      agent for colorectal cancer, and many studies have examined possible
      associations. However, the conclusions were inconsistent or even contradictory,
      so we performed a meta-analysis based on published case-control studies to
      explore if green tea is indeed a protective factor. METHODS: PubMed was searched
      up to May 10th, 2012 for relevant studies, and references of included studies
      were manually searched. Finally 13 eligible studies, involving 12,636 cases and
      38,419 controls were identified. After data extraction, a meta-analysis was
      performed using CMA v2 software. RESULTS: The results indicated there may be a
      weak but not statistically significant reduced risk of colorectal cancer with
      high dose of green tea intake (OR=0.95, 95% CI:0.81-1.11, p=0.490.69-0.98). This
      protective effect was also found in all subgroups, except in American and
      European populations. Sensitivity analysis indicated the result to be robust.
      Publication bias was not detected by either funnel plot or Egger tests.
      CONCLUSION: The results of this meta-analysis indicate a weak lower tendency for
      colorectal cancer development with green tea consumption, but available
      epidemiologic data are insufficient to conclude that green tea may protect
      against colorectal cancer in humans.

PMID- 22994722
TI  - Anxiety and symptom assessment in Turkish gynecologic cancer patients receiving
      chemotherapy.
AB  - Diagnosis and treatment procedures in cancers and resulting anxiety negatively
      affect the individual and the family. Particularly treatment methods may generate
      psychological symptoms. The aim of this study was to determine the level of such
      symptoms in Turkish gynecologic cancer patients receiving chemotherapy. A total
      of 41 patients who were referred to our gynecologic oncology research clinic
      between January-March 2012, receiving 3 months or more chemotherapy and who
      agreed to participate were enrolled in study. All the data were collected using a
      personal information form, Edmonton Symptom Assesment System and State-Trait
      Anxiety Inventory. Patients received highest point average from fatigue symptom
      (6.53+/-2.67) and lowest point average from dyspnea (1.53+/-3.03) according to
      Edmonton Symptom Assesment System. The mean State Anxiety score of patients was
      43.1+/-9.77 and mean Trait Anxiety score was 46.7+/-7.01. Comparing symptoms of
      patients and mean State Anxiety score it was found that there was a statistically
      significant corelation with symptoms like pain (p<0.05), sadness (p<0.001),
      insomnia (p<0.05), state of well being (p<0.001) and dyspnea (p<0.05). Similarly
      comparing symptoms of patients and mean Trait Anxiety score demonstrated
      significant correlations for fatigue (p<0.05), sadness (p<0.01), insomnia
      (p<0.01) and state of well-being (p<0.01). As a result, patients with
      gynecological cancers experienced symptoms related to chemotherapy and a moderate
      level of anxiety. In accordance, appropriate interventions should recommended for
      the evaluation and improvement of anxiety and symptoms related to treatment in
      cancer patients.

PMID- 22994723
TI  - Reliability and validity of Turkish versions of the child, parent and staff
      cancer fatigue scales.
AB  - This study was designed to adapt the Turkish versions of scales to evaluate
      fatigue in children with cancer from the perspectives of the children, parents
      and staff. The objective of this study was to validate "Child Fatigue Scale-24
      hours" (CFS-24 hours), "Parent Fatigue Scale-24 hours" (PFS-24 hours) and "Staff
      Fatigue Scale-24 hours" (SFS-24 hours) for use in Turkish clinical research
      settings. Translation of the scales into Turkish and validity and reliability
      tests were performed. The validity of the translated scales was assessed with
      language validity and content validity. The reliability of the translated scales
      was assessed with internal consistency. The scales were evaluated by considering
      the following: calculation of the Cronbach alpha coefficient for parallel form
      reliability with 52 pediatric cancer patients, 86 parents and 43 nurses. The
      internal consistency was estimated as 0.88 for the Child Fatigue Scale-24 hours,
      0.77 for the Parent Fatigue Scale-24 hours, and 0.72 for the Staff Fatigue Scale
      24 hours (Cronbach's alpha). The Turkish version of the Child Fatigue Scale-24
      hours, the Parent Fatigue Scale-24 hours and the Staff Fatigue Scale-24 hours
      were judged reliable and valid instruments to assess fatigue in children and
      showed good psychometric properties. These scales should assist in understanding
      to what extent initiatives can minimize or eliminate fatigue. Our scales are
      recommended for further studies and use in pediatric oncology clinics as routine
      measurements and nursing initiatives should be planned accordingly.

PMID- 22994724
TI  - Physical activity and risk of lung cancer: a meta-analysis of prospective cohort
      studies.
AB  - BACKGROUND: Previous studies investigating the association of physical activity
      with risk of lung cancer reported conflicting results. In order to update and
      improve available evidence on any link, a meta-analysis was performed. METHOD: We
      searched the PubMed database for prospective cohort studies investigating the
      relation of physical activity with risk of lung cancer. The pooled relative risk
      (RR) with its 95% confidence intervals (95%CI) was used to assess the
      association. RESULTS: We included 14 prospective studies with a total of
      1,644,305 participants, with 14,074 incident lung cancer cases documented during
      follow-up. Meta-analysis of all 14 studies suggested both high and medium levels
      of physical activity to be associated with decreased risk of lung cancer compared
      to the reference group with low level of physical activity (for high level, RR =
      0.77, 95%CI 0.73-0.81, P < 0.001; for medium level, RR = 0.87, 95%CI 0.83-0.90, P
      < 0.001). Subgroup analyses by gender found obvious associations in both men and
      women. No publication bias was observed. CONCLUSION: Our findings suggest that
      high and medium levels of physical activity have a beneficial effect on lung
      cancer by reducing the overall risk of tumour development among both men and
      women.

PMID- 22994725
TI  - Perineural invasion independent prognostic factors in patients with gastric
      cancer undergoing curative resection.
AB  - OBJECTIVE: The prognostic significance of perineural invasion (PNI) in gastric
      cancer has been previously investigated but not clearly clarified. The objective
      of our study was to investigate the role of PNI as prognostic factor in patients
      undergoing curative surgical resection and without distant metastasis in
      comparison with other clinicopathological factors. METHODS: Between 2001 and
      2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded
      in hospital based registries. PNI was assessed as positive when cancer cells were
      seen in the perinerium or neural fascicles intramurally. Categorical and
      continuous variables were summarized using descriptive statistics and compared
      using chi-square and Mann-Whitney U tests, respectively. Cancer related survival
      rates were estimated by the Kaplan-Meier method. RESULTS: PNI was positive in 211
      of 287 cancers (73%), with a positive relation to lymph node metastases and
      advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic
      and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival
      of the PNI positive patients was significantly shorter than that of their PNI
      negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate
      analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21,
      95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph
      node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age,
      gender, tumour localization, stage, histologic type, and surgery procedure.
      CONCLUSIONS: PNI positivity in gastric cancers was related mural invasion, lymph
      node involvement, advanced stage and lymphatic and venous blood vessels. The
      presence of PNI appeared as an independent prognostic factor on survival on
      multivariate analysis, not influenced by tumor stage, lymph node metastases and
      other classical factors.

PMID- 22994727
TI  - Direct costs of cervical cancer management in Morocco.
AB  - BACKGROUND: For cervical cancer the epidemiological profile is poorly known in
      Morocco and no data is available concerning the direct medical costs. The purpose
      of this work is to estimate the direct cost of medical management of invasive
      cervical cancer during the first year after diagnosis in Morocco. METHODS: The
      estimation of direct costs of medical management of invasive cervical cancer
      during the first year after diagnosis in Morocco is based on the estimation of
      individual cost in each stage which covers diagnosis, treatment and follow-up
      during first year. The cost was estimated per patient and whole cycle-set using
      the costs for each drug and procedure as indicated by the Moroccan National
      Agency for Health Insurance. Extrapolation of the results to the whole country
      was used to calculate the total annual cost of cervical cancer treatments in
      Morocco. RESULTS: Overall approximately 1,978 new cases of cervical cancer occur
      each year in Morocco. The majority (82.96%) of these cases were diagnosed at a
      late stage (stage II or more). The cost of one case of cervical cancer depends on
      stage of diagnosis, the lowest cost is $382 for stage Cis followed by the cost of
      stage IA1 for young women (<40 years) which is $2,952. The highest cost is for
      stage IV, which is $7,827. The total cost of cervical cancer care for one year
      after diagnosis is estimated at $13,589,360. The share allocated to treatment is
      the most important part of the global care budget with an annual sum of
      $13,027,609 whereas other cost components are represented as follows: $435,694
      for annual follow-up activity and $126,057 for diagnosis and preclinical staging.
      CONCLUSION: This study provides health decision-makers with a first estimate of
      costs and the opportunity to achieve the optimal use of available data to
      estimate the needs of health facilities in Morocco.

PMID- 22994726
TI  - Cervical cancer in Morocco: epidemiological profile from two main oncological
      centers.
AB  - BACKGROUND: In Morocco, the epidemiological profile of cervical cancer is not
      well established. The focus of the present study was both epidemiological and
      pathological characteristics. METHODS: For all cases of cervical cancer treated
      between 2003 and 2007 in the National Institute of Oncology and the Oncology
      Department of the IbnRochd hospital (Casablanca), 900 cases were randomly
      selected. RESULTS: The mean age was 52.1+/-11.8 years. The most (90.5%)
      represented histological type was squamous cell carcinoma. For more than 57.0%
      cases the mean distance between patient's origin and center of treatment was
      greater than 100 km. According to the FIGO classification, only 17.2% of patients
      were identified as being in early stages (0 and I). For 72.2% patients the follow
      up did not exceed 2 years. At 1 year of following-up 55.8% of patients were alive
      and 43.4% were lost to following-up. CONCLUSION: Our study addressed the issue of
      the burden of cervical cancer in Morocco. The result provides a basis for
      decision-makers for the development of strategic measures to implement the fight
      against cervical cancer in Morocco.

PMID- 22994728
TI  - Genetic variants of CYP2D6 gene and cancer risk: a HuGE systematic review and
      meta-analysis.
AB  - OBJECTIVE: Genetic polymorphisms in metabolic enzymes are associated with
      numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the
      CYP2D6 gene have been reported to associate with cancer susceptibility. However,
      the results are controversial. The aim of this Human Genome Epidemiology (HuGE)
      review and meta-analysis was to summarize the evidence for associations. METHODS:
      Studies focusing on the relationship between CYP2D6 gene polymorphisms and
      susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase,
      Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two
      independent reviewers and the meta-analysis was performed with Review Manager
      Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95%
      confidence intervals (95%CIs) were calculated. RESULTS: According to the
      inclusion criteria, forty-three studies with a total of 7,009 cancer cases and
      9,646 healthy controls, were included in the meta-analysis. The results showed
      that there was a positive association between heterozygote (GC) of rs1135840 and
      cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that
      homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58,
      95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of
      rs16947 and heterozygote (A/del) of rs35742686 had negative associations with
      cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94,
      P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). CONCLUSION: This meta
      analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis
      of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might
      increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier
      (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective
      factors.

PMID- 22994729
TI  - Prognostic significance of overexpression of EZH2 and H3k27me3 proteins in
      gastric cancer.
AB  - The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27
      (H3K27me3) protein can repress gene transcription, and their aberrant expression
      has been observed in various human cancers. This study determined their
      expression levels in gastric cancer tissues with reference to clinicopathological
      features and patient survival. We collected 117 gastric cancer and corresponding
      normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117
      (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in
      contrast to only 5.41% and 7.25% of normal gastric mucosa specimens,
      respectively. Kaplan-Meier survival data showed the average overall and disease
      free survival of EZH2 high expression patients was 25.2 and 20.2 months,
      respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months).
      The average overall survival and disease-free survival of high H3K27me3
      expression patients was 23.4 and 17.4 months, shorter than without H3K27me3
      expression (37.6 and 34.5 months). The average overall survival and disease-free
      survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9
      months, respectively, shorter than that with either alone (34.7 and 31.2 months)
      or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression
      analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and
      clinical stage were all independent prognostic factors for predicting patient
      survival. This study demonstrated that detection of both EZH2 and H3K27me3
      proteins can predict poor survival of gastric cancer patients, superior to single
      protein detection. In addition, H3K27me3 and EZH2 protein expression could
      predict lymph node metastasis.

PMID- 22994730
TI  - Sun exposure and the risk of prostate cancer in the Singapore Prostate Cancer
      Study: a case-control study.
AB  - BACKGROUND: Most of the epidemiology studies on the effects of sun exposure and
      prostate cancer were conducted among the temperate countries of North America and
      Europe. Little is known about the influence on Asian populations. The purpose of
      current study was to evaluate any association of sun exposure with risk of
      prostate cancer in Chinese, Malays and Indians who reside in the tropics.
      METHODS: The Singapore Prostate Cancer Study is a hospital-based case-control
      study of 240 prostate cancer incident cases and 268 controls conducted in
      Singapore between April 2007 and May 2009. Detailed information on outdoor
      activities in the sun, skin colour, sun sensitivity and other possible risk
      factors were collected in personal interviews. Cases were further classified by
      Gleason scores and TNM staging. Odds ratios (OR) and 95% confidence intervals
      (CI) were calculated using unconditional logistic regression analysis, adjusted
      for age, ethnicity, education, family history of any cancers, BMI and skin
      colour. RESULTS: We found that prostate cancer risk was increased in subjects
      with black/dark-brown eyes (OR 5.88, 95%CI 3.17-10.9), darker skin colour e.g.
      tan/dark brown/black (OR 7.62, 95%CI 3.41-17.0), frequent sunburn in lifetime (OR
      4.30, 95%CI 1.7-11.2) and increased general sun exposure in adulthood per week
      (OR 2.03, 95%CI 1.09-3.81). The increased risk was consistent for high grade
      tumours and advanced stage prostate cancers. CONCLUSION: The findings from this
      study suggest that excessive sun exposure is a risk factor for prostate cancer in
      Asians.

PMID- 22994731
TI  - Presence of anemia and poor prognostic factors in patients with endometrial
      carcinoma.
AB  - This study evaluated the relationship between pretreatment hemoglobin (Hb) and
      prognostic factors in Thai patients with endometrial cancer. Medical records of
      228 patients who had undergone surgery between January 2005 and December 2007
      were retrospectively reviewed. Associations between clinicopathological variables
      and pretreatment Hb levels were described using Pearson's chi square test or two
      tailed Fisher's exact test. Survival analysis was performed with Kaplan-Meier
      estimates. Univariate and Cox-regression models were used to evaluate the
      prognostic impact of various factors, including Hb levels, in term of disease
      free survival. The median duration of follow-up was 38.2 months. Eighty-nine
      patients (39%) had a preoperative Hb level of <12 g/dL, these having
      significantly higher rates of non-endometrioid histology, advanced FIGO stage,
      lymphovascular space invasion, cervical involvement, adnexal involvement,
      positive peritoneal cytology, and lymph node involvement than patients with Hb
      >=12 g/dL. The 5-year disease-free and overall survival were significantly lower
      in patients with pretreatment Hb levels <12 g/dL compared with those with Hb >=12
      g/dL (79.3% vs. 89.2%, p=0.044 and 87.6% vs. 99.3%, p<0.001, respectively). In
      the multivariate analysis only histology, myometrial invasion, and lymphovascular
      invasion proved to be independent prognostic factors, whereas tumor grading,
      stage, cervical involvement, adnexal involvement, positive peritoneal cytology,
      lymph node involvement, and low Hb were not. In conclusion, presence of anemia
      before treatment may reflect poor prognostic factors in patients with endometrial
      cancer and low pretreatment hemoglobin level may have a prognostic impact on
      clinical outcome.

PMID- 22994732
TI  - Association between insulin-like growth factor-2 expression and prognosis after
      transcatheter arterial chemoembolization and octreotide in patients with
      hepatocellular carcinoma.
AB  - OBJECTIVE: To investigate the association between the change of IGF-2 level in
      serum after transcatheter arterial chemoembolization (TACE) and hepatocellular
      carcinoma (HCC) progression, especially in relation to metastasis. METHODS: IGF-2
      in serum was measured by quantitative sandwich enzyme-linked immunosorbent assay
      before, 3 days and 4 weeks after TACE in 60 patients with HCC. The occurrence of
      HCC metastasis was also evaluated, 3 months after TACE. RESULTS: (1) The average
      serum level of IGF-2 in the 60 patients with HCC was 136.5 +/- 87.3 pg/ml; (2) A
      tendency for increase was observed with heterogenous uptake of octreotide and
      portal vein thrombosis. Metastatic foci were found in 37/38 patients in the group
      with IGF-2 increasing (97.0%), in contrast to 3/22 (13.6%) patients with IGF-2
      decrease. CONCLUSION: The increase of IGF-2 level in serum appears to be
      associated with the occurrence of metastatic HCC after TACE and chemotherapy.

PMID- 22994733
TI  - Breast cancer survivors' efforts to renew and preserve their health in Taiwan.
AB  - AIMS: This study was designed to describe the personal life experiences of breast
      cancer survivors regarding their efforts to recover and preserve their health in
      Taiwan. METHOD: The study utilized a qualitative research method, wherein
      purposive sampling, one-on-one, face-to-face, in-depth semi-structured interviews
      were conducted. The data were then analyzed using content analysis. Data were
      saturated after interviewing 15 cancer survivors. RESULTS: Three common themes
      emerged: introspection on the cause of the cancer, realization of a harmonized
      lifestyle, and reflecting on the strong will to survive. CONCLUSIONS: These
      findings are helpful in understanding the relationship between breast cancer
      survival and individual efforts to restore and preserve health.

PMID- 22994734
TI  - Effects of multiple-target anti-microRNA antisense oligodeoxyribonucleotides on
      proliferation and migration of gastric cancer cells.
AB  - BACKGROUNDS: To investigate the inhibiting effects of multi-target anti-microRNA
      antisense oligonucleotide (MTg-AMOs) on proliferation and migration of human
      gastric cancer cells. METHODS: Single anti-microRNA antisense oligonucleotides
      (AMOs) and MTg-AMOs for miR-221, 21, and 106a were designed and transfected into
      SGC7901, a gastric cancer cell line, to target the activity of these miRNAs.
      Their expression was analyzed using stem-loop RT-PCR and effects of MTg-AMOs on
      human gastric cancer cells were determined using the following two assay methods:
      CCK8 for cell proliferation and transwells for migration. RESULTS: In the CCK-8
      cell proliferation assay, 0.6 MUmol/L was selected as the preferred concentration
      of MTg-AMOs and incubation time was 72 hours. Under these experimental
      conditions, MTg-AMOs demonstrated better suppression of the expression of miR
      221, miR-106a, miR-21 in gastric cancer cells than that of single AMOs (P =
      0.014, 0.024; 0.038, respectively). Migration activity was also clearly decreased
      as compared to those in randomized and blank control groups (28 +/- 4 Vs 54 +/-
      3, P <0.01; 28 +/- 4 Vs 59 +/- 4, P < 0.01). CONCLUSIONS: MTg-AMOs can
      specifically inhibit the expression of multiple miRNAs, and effectively
      antagonize proliferation and migration of gastric cancer cells promoted by
      oncomirs.

PMID- 22994735
TI  - Changing trends of colorectal carcinoma in Nepalese young adults.
AB  - INTRODUCTION: Colorectal carcinoma (CRC) is the most common gastrointestinal
      malignancy in the older population, but it is also quite frequent among young
      adults in developing countries. The aim of this study was to update the trends of
      clinicopathological features of CRC in young Nepalese. METHODS: A retrospective
      comparative study on the data retrieved from the surgical records of all patients
      between 20 to 39 years of age with CRC was carried out for periods of 5 years
      each from 1999 to 2003 (early) and 2004 to 2008 (recent), treated at Tribhuvan
      University Teaching Hospital, Kathmandu, Nepal. RESULTS: The number of young
      adults with CRC increased from 28 to 34. However, the proportion of young
      patients in both groups was 28% of all CRC patients. The mean ages were 34+/-4.7
      and 31.8+/-5.1 years in early and recent 5 years, respectively, and the male
      female ratio changed from 2:3 to 4:3. Abdominal pain as the most common
      presenting symptom was replaced by bleeding per rectum in recent years. The mean
      duration from onset of symptoms to seeking medical advice decreased from 7.8
      months to 5.6 months in recent years. More patients (85.3%) were subjected to
      endoscopic examination in recent years than early years (60.7%) and right colonic
      cancer increased from 10.7% to 26.5%. However, the rectum was the commonest site
      in both early (71.4%) and recent (50%) groups. CRC was detected significantly at
      an earlier stage (7.1% vs 32.4%) in recent years with large proportion of
      modified Dukes B stage. Poorly differentiated adenocarcinoma was the predominant
      histology in both groups (50% vs 60.7%). Curative resection had risen in recent
      years (39.3% vs 73.6%). CONCLUSION: CRC among Nepalese young adults accounts for
      a high incidence (28%) of all CRC cases. Although right sided colonic cancer has
      been increasing, rectum is the commonest site. There is also an increasing trend
      for diagnosis at earlier stages of the disease which can be treated with curative
      intent.

PMID- 22994736
TI  - Comparison of WHO and RECIST criteria for evaluation of clinical response to
      chemotherapy in patients with advanced breast cancer.
AB  - When patients with advanced breast cancer (ABC) are treated with neoadjuvant
      chemotherapy (NACT), efficacy is monitored by the extent of tumor shrinkage.
      Since their publication in 1981, World Health Organization (WHO) guidelines have
      been widely practiced in clinical trials and oncologic practice, for standardized
      tumor response evaluation. With advances in cancer treatment and tumor imaging, a
      simpler criterion based on one-dimensional rather than bi-dimensional (WHO) tumor
      measurement, named Response Evaluation Criteria in Solid Tumors (RECIST) was
      introduced in 2000. Both approaches have four response categories: complete
      response, partial response, stable disease and progressive disease (PD). Bi
      dimensional measurement data of 151 patients with ABC were analysed with WHO and
      RECIST criteria to compare their response categories and inter criteria
      reproducibility by Kappa statistics. There was 94% concordance and 9/151 patients
      were re-categorized with RECIST including 6/12 PD cases. RECIST therefore under
      estimates and delays diagnosis of PD. This is undesirable because it may delay or
      negate switch over to alternate therapy. Analysis was repeated with a new
      criteria named RECIST-Breast (RECIST-B), with a lower threshold for PD (>=10%
      rather than >=20% increase of RECIST). This showed higher concordance of 97% with
      WHO criteria and re-categorization of only 4/151 patients (1/12 PD cases). RECIST
      B criteria therefore have advantages of both ease of measurement and calculations
      combined with excellent concordance with WHO criteria, providing a practical
      clinical tool for response evaluation and offering good comparison with past and
      current clinical trials of NACT using WHO guidelines.

PMID- 22994737
TI  - Angiogenesis and lymphangiogenesis in oral squamous cell carcinoma: comparison of
      Japanese and Indian cases.
AB  - A comparative study between 17 Japanese and 19 Indian patients with oral squamous
      cell carcinomas (OSCCs) revealed that the tumour prognostic indicator mean vessel
      density (MVD) count for angiogenesis was relatively high at 57.1 in Indian as
      compared to 39.3 in Japanese (P=0.001) cases, whereas the lymph-vessel density
      (LVD) count for lymphangiogenesis was lower (12.8 vs 48.0, P=0.002). Both male
      and female Indians had higher MVD counts, but LVD counts were only slightly lower
      in females. MVD count was relatively high among the cases below 65 years old in
      both the countries (P=0.4). Japanese cases with Tongue cancer had higher MVD
      count, but the Indian cases had lower LVD counts. Size-wise, T2 and T3 had higher
      counts of MVD both in Indian and Japanese cases. MVD and LVD count was higher in
      grades II and III both in Japanese and Indian cases. There was insignificant
      difference of the MVD counts among smokers, but the tobacco chewers in Indian
      cases had higher counts of MVD and LVD (P value by Bartlett test 0.35, 0.57
      respectively). The hot-spots of tumour sites had variable rates of lymphocyte
      infiltration showed higher MVD counts in all the cases. Although the clinical
      characteristics and demographic variables usually relate to MVD and LVD counts,
      the tendency of higher values, especially among tobacco chewers, identified as
      the highest risk group for occurrence of oral cancer needs to be investigated
      further.

PMID- 22994738
TI  - Knockdown of HMGN5 expression by RNA interference induces cell cycle arrest in
      human lung cancer cells.
AB  - HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding
      protein) family which may function as a nucleosomal binding and transcriptional
      activating protein. Overexpression of HMGN5 has been observed in several human
      tumors but its role in tumorigenesis has not been fully clarified. To investigate
      its significance for human lung cancer progression, we successfully constructed a
      shRNA expression lentiviral vector in which sense and antisense sequences
      targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory
      effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were
      demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing
      to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU
      incorporation and colony formation assays. Furthermore, flow cytometry analysis
      showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1
      phase and decreased the populations of A549 and H1299 cells at the S and G2/M
      phases. Taken together, these results suggest that HMGN5 is directly involved in
      regulation cell proliferation in A549 and H1299 cells by influencing signaling
      pathways involved in cell cycle progression. Thus, our finding suggests that
      targeting HMGN5 may be an effective strategy for human lung cancer treatment.

PMID- 22994739
TI  - Estimation of denominators--new approach for calculating of various rates in
      cancer registries.
AB  - In this study, cancer incidence data were assessed to provide various rates of
      five year age groups for a given year, lying between two census years. The
      individual exponential growth rate method is most useful in both population-based
      and non-population cased cancer registries in India to estimate the population by
      five yearly age groups and also find the rates of crude rates, age standard rates
      and cumulative rates. This method has been shown to endure from bias and often
      results sacrificing the overall growth rate and correction factor must be needful
      in five year age group population to maintain it. A second method, the difference
      distribution method is also able to maintain the overall growth rate and overcome
      the bias in estimation of five yearly age group populations. From this point of
      view these methods serving a new technique for population estimation by five
      yearly age groups for inter census years.

PMID- 22994740
TI  - MSP58 knockdown inhibits the proliferation of esophageal squamous cell carcinoma
      in vitro and in vivo.
AB  - Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor
      prognosis. Understanding the molecular mechanisms underlying esophageal cancer
      progression is a high priority for improved EC diagnosis and prognosis. Recently,
      MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas.
      However, little is known about its function in esophageal carcinomas. We
      therefore examined the effects of MSP58 knockdown on the growth of esophageal
      squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a
      better understanding of its potential as a tumor therapeutic target. We employed
      lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of
      MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of
      ESCC cell proliferation and colony formation in vitro. Furthermore, flow
      cytometry and western blot analyses revealed that MSP58 depletion induced cell
      cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably,
      the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts
      in nude mice. Our results suggest that MSP58 may play an important role in ESCC
      progression.

PMID- 22994741
TI  - Hyperthermia promotes apoptosis and suppresses invasion in C6 rat glioma cells.
AB  - Gliomas are a group of heterogeneous primary central nervous system tumors.
      Hyperthermia has proven to be a potential therapeutic tool for cancers in the
      clinic. However, the molecular mechanisms of hyperthermia remain unclear. The
      objective of this study was to investigate the effects of hyperthermia on the
      invasiveness in C6 glioma cells and related molecular pathways. Here our data
      show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF
      alpha) and decreased C6 glioma cell migration and invasive capability at 30, 60,
      120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120
      min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression
      to be increased and nuclear factor-kappa B (NF-kappaB) protein expression
      decreased. Based on the results, we conclude that hyperthermia alone reduced
      invasion of C6 glioma cells through stimulating TNF-alpha signaling to activate
      apoptosis, enhancing P38 MAPK expression and inhibiting the NF-kappaB pathway, a
      first report in C6 rat glioma cells.

PMID- 22994742
TI  - Predictive role of glutathione-S-transferase gene polymorphisms in risk and
      prognosis of hepatocellular carcinoma.
AB  - AIM: We conducted a prospective study in an Chinese population to detect
      associations of GSTM, GSTT and GSTP polymorphisms with hepatocellular carcinoma
      (HCC), and analyze roles in determining survival outcome. METHODS: A prospective
      follow-up study was conducted with 476 HCC patients and 481 controls collected
      from May 2005 to May 2007. All patients were followed up until the end of Dec.
      2011. GSTM1, GSTT1 and GSTP1 genotyping were performed by PCR-CTPP methods.
      RESULTS: Null GSTM1 carriers had a 1.64 fold risk of HCC compared with non-null
      genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1
      IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months
      (range: 1 to 78 months). Individuals with null GSTM1 genotype had better survival
      of HCC than non-null genotype carriers (HR=0.71, 95%CI=0.45-0.95). Similarly,
      GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIe
      genotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1
      Val/Val who received chemotherapy had lower risk of death from HCC than those
      without chemotherapy. CONCLUSION: This study indicated carriage of null GSTM1 and
      GSTP1 Val/Val genotypes to have roles in susceptibility to and survival from HCC.

PMID- 22994743
TI  - Whole brain radiotherapy plus chemotherapy in the treatment of brain metastases
      from lung cancer: a meta-analysis of 19 randomized controlled trails.
AB  - OBJECTIVE: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT)
      plus chemotherapy versus WBRT alone for treating brain metastases (BM) from lung
      cancer by performing a meta-analysis based on randomized controlled trials
      (RCTs). METHODS: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM, CNKI, and VIP
      databases were searched for relevant RCTs performed between January 2000 and
      March 2012. After quality assessment and data extraction, the meta-analysis was
      performed using the RevMan 5.1 software, with funnel plot evaluation of
      publication bias. RESULTS: 19 RCTs involving 1,343 patients were included. The
      meta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy
      was more effective with regard to the objective response rate (OR = 2.30, 95% CI
      = 1.79-2.98; P < 0.001); however, the incidences of gastrointestinal reactions
      (RR = 3.82, 95% CI = 2.33-6.28, P <0.001), bone marrow suppression (RR = 5.49,
      95% CI = 3.65-8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39-86.59;
      P = 0.20), leukopenia (RR = 3.13, 95% CI = 1.77-5.51; P < 0.001), and neutropenia
      (RR = 2.75, 95% CI = 1.61-4.68; P < 0.001) in patients treated with WBRT plus
      chemotherapy were higher than with WBRT alone. There was no obvious publication
      bias detected. CONCLUSION: WBRT plus chemotherapy can obviously improve total
      efficacy rate, but also increases the incidence of adverse reactions compared to
      WBRT alone. From the limitations of this study, more large-scale, high-quality
      RCTs are suggested for further verification.

PMID- 22994744
TI  - Curcumin effect on MMPs and TIMPs genes in a breast cancer cell line.
AB  - Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix
      metalloproteinases (MMPs) play an important role in remodeling the extracellular
      matrix and their activities are regulated by tissue inhibitor of
      metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of
      great significance. In this study, the effect of CM is investigated on metastatic
      MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a
      mixture of DMEM and Ham's F12 medium and treated with different concentrations of
      CM (10, 20 and 40 MUM for various lengths of time. Reverse transcription followed
      by quantitative real time PCR was used to detect the gene expression levels of
      MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by
      one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes
      were up-regulated after 48 hours of treatment, their over-expression being
      accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a
      concentration- and time-dependent manner. These results suggest that curcumin
      plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up
      regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

PMID- 22994745
TI  - Proteomic analysis of serum of women with elevated Ca-125 to differentiate
      malignant from benign ovarian tumors.
AB  - Clinically, elevated cancer antigen 125 (CA-125) in blood predicts tumor burden
      in a woman's body, especially in the ovary, but cannot differentiate between
      malignant or benign. We here used intensive modern proteomic approaches to
      identify predictive proteins in the serum of women with elevated CA-125 to
      differentiate malignant from benign ovarian tumors. We identified differentially
      expressed proteins in serum samples of ovarian cancer (OC) patients, benign
      ovarian tumor (BT) patients, and healthy control women using mass spectrometry
      based quantitative proteomics. Both the OC and BT patients had elevated CA-125.
      Quantitation was achieved using isobaric tags for relative and absolute
      quantitation. We obtained 124 quantified differential serum proteins in OC
      compared with BT. Two proteins, apolipoprotein A-4 (APOA4) and natural resistance
      associated macrophage 1, were verified using Western blotting. Proteome profiling
      applied to OC cases identified several differential serum proteins in the serum
      of women with elevated CA-125. A novel protein, APOA4, has the potential to be a
      marker for malignant tumor differentiation in the serum of women with elevated CA
      125.

PMID- 22994746
TI  - Obesity and screening compliance for breast and cervical cancer in Korean women.
AB  - PURPOSE: This study was performed to assess whether the weight status is
      associated with screening rates of breast and cervical cancer in Korean women.
      METHODS: Study participants included women aged between 30 and 80 years from the
      4th Korea National Health and Nutrition Examination Survey from 2007 to 2009.
      Body mass index was classified into ~18.4 kg/m2 (underweight), 18.5~22.9 kg/m2
      (normal), 23~24.9 kg/m2 (overweight), 25.0~29.9 kg/m2 (moderate obesity) and 30.0
      kg/m2~ (severe obesity) according to the Asia Pacific Standards of WHO
      recommended definition of obesity. Screening rates of breast and cervical cancer
      were estimated by the recommendation of the National Cancer Screening Program of
      the National Cancer Center, Korea. RESULTS: The overall screening rates for
      breast and cervical cancer were 51.3% and 50.1%, respectively. After covariate
      adjustment, the screening rates for breast cancer (adjusted odds ratio, 0.70; 95%
      confidence interval, 0.51 to 0.97) and cervical cancer (adjusted odds ratio,
      0.71; 95% confidence interval, 0.53 to 0.94) were significantly lower in the
      women with severe obesity. CONCLUSION: Obesity is associated with lower
      compliance with breast and cervical cancer screening guidelines in Korean women.

PMID- 22994747
TI  - Metformin inhibits growth of hepatocellular carcinoma cells by inducing apoptosis
      via mitochondrion-mediated pathway.
AB  - Recently, population-based studies of type 2 diabetes patients have provided
      evidence that metformin treatment is associated with a reduced cancer incidence
      and mortality, but its mode of action remains unclear. Here we report effects of
      metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular
      mechanisms of metformin activity. Our research indicates that metformin displays
      anticancer activity against HCC through inhibition of the mTOR translational
      pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and
      subsequent cell apoptosis through the mitochondrion-dependent pathway.
      Furthermore, we showed that metformin strongly attenuated colony formation and
      dramatically inhibited Hep-G2 tumor growth in vivo. In conclusion, our studies
      suggested that metformin might have potential as a cytotoxic drug in the
      prevention and treatment of HCC.

PMID- 22994748
TI  - Prognostic value of HPV18 DNA viral load in patients with early-stage
      neuroendocrine carcinoma of the uterine cervix.
AB  - OBJECTIVES: To evaluate the clinicopathologic correlation and prognostic value of
      HPV18 DNA viral load in patients with early-stage cervical neuroendocrine
      carcinoma (NECA). METHODS: Formalin-fixed, paraffin- embedded tissue of cervical
      NECA patients with known HPV18 infection and clinicopathologic data including
      follow-up results were collected. The HPV18 DNA load was assessed with
      quantitative PCR targeting the HPV18 E6E7 region. RESULTS: Twenty-one patients
      with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load
      ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression,
      observed in 10 cases (48%), was not significantly associated with any
      clinicopathologic variables. However, the group of patients with progressive
      disease tended to have a higher rate of pelvic lymph node metastasis (50% versus
      9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17
      copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a
      cut-off viral load value of 5.00 copies/cell, the group of patients with viral
      load <=5.00 copies/cell had a significantly shorter disease-free survival than
      the group with viral load >5.00 copies/cell (p=0.028). The group with a lower
      viral load also tended to have a higher rate of disease progression (75% versus
      31%, p=0.080). No significant difference in the other clinicopathologic variables
      between the lower and higher viral load groups was identified. CONCLUSION: THPV18
      DNA viral load may have a prognostic value in patients with early-stage NECA of
      the cervix. A low viral load may be predictive of shortened disease-free survival
      in these patients.

PMID- 22994749
TI  - Intensity-modulated radiotherapy for nasopharyngeal carcinoma: Penang General
      Hospital experience.
AB  - PURPOSE: To study the overall treatment time (OTT) and acute toxicity of
      intensity-modulated radiotherapy (IMRT) treatment for nasopharyngeal carcinoma
      (NPC). METHODS: This retrospective study covered all NPC patients who underwent
      radical IMRT treatment at the Penang General Hospital from June 2011 to February
      2012. Patients of any age and stage of disease with histologically proven
      diagnosis were included. Information was collected on patient demographics,
      clinical stage, treatment received, including any neoadjuvant and/or concurrent
      chemotherapy, acute toxity and completion of IMRT within the OTT. RESULTS: A
      total of 26 NPC patients were treated with IMRT during the study period; 88.5%
      had stage III/IV disease. 45.2% received neo-adjuvant chemotherapy while 50.0%
      were given concurrent chemo-irradiation. All patients completed the treatment and
      92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3%
      having grade 2. Severe grade III/IV acute toxicity occurred in 73.1% of patients,
      the commonest of which was oral mucositis (57.6%). This was followed by dysphagia
      which occurred in 53.8%, skin reactions in 42.3% and weight loss in 19.2%.
      However, haematological toxicity was mild with only one patient having
      leucopaenia. CONCLUSION: IMRT treatment for NPC is feasible in our center. More
      importantly, it can be delivered within the 7 weeks OTT in the majority of
      patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal
      nutritional and analgesic support is required throughout the treatment.

PMID- 22994750
TI  - Novel mononuclear ruthenium(II) compounds in cancer therapy.
AB  - The present study was conducted to evaluate in vivo anticancer activity of two
      novel mononuclear ruthenium(II) compounds, namely Ru(1,10-phenanthroline)2(2
      nitro phenyl thiosemicarbazone)Cl2 (Compound R1) and Ru (1,10-phenanthroline)2(2
      hydroxy phenyl thiosemicarbazone)Cl2 (Compound R2) against Ehrlich ascites
      carcinoma (EAC) mice and in vitro cytotoxic activity against IEC-6 (small
      intestine) cell lines and Artemia salina nauplii using MTT [(3-(4,5
      dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide)] and BLT [brine shrimp
      lethality] assays respectively. The test ruthenium compounds at the doses 2 and 4
      mg/kg body weight showed promising biological activity, especially in decreasing
      tumor volume, viable ascites cell counts and body weights. These compounds
      prolonged the life span (% ILS), mean survival time (MST) of mice bearing-EAC
      tumor. The results for in vitro cytotoxicity against IEC-6 cells showed the
      ruthenium compound R2 to have significant cytotoxic activity with a IC50 value of
      20.0 MUg/mL than R1 (IC50=78.8 MUg/mL) in the MTT assay and the LC50 values of R1
      and R2 compounds were found to be 38.3 and 43.8 MUg/mL respectively in the BLT
      assay. The biochemical and histopathological results revealed that there was no
      significant hepatotoxicity and nephrotoxicity associated with the ruthenium
      administration to mice.

PMID- 22994751
TI  - Association between XPD Asp312Asn polymorphism and esophageal cancer
      susceptibility: a meta-analysis.
AB  - OBJECTIVE: To investigate the association between xeroderma pigmentosum group D
      (XPD) Asp312Asn polymorphism and esophageal cancer (EC) susceptibility by meta
      analysis. METHODS: We searched PubMed up to April 9th, 2012, to identify relevant
      papers, and 8 published case-control studies including 2165 EC patients and 3141
      healthy controls were yielded. Odds ratios (ORs) with relevant 95% confidence
      intervals (CIs) were applied to assess the association between XPD Asp312Asn
      polymorphism and EC susceptibility with the Comprehensive Meta-Analysis software,
      version 2.2. RESULTS: Overall, the meta-analysis results suggested the XPD
      Asp312Asn polymorphism to be significantly associated with EC susceptibility
      [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.20, 95%CI=1.05-1.36, p=0.01; and Asp/Asn vs.
      Asp/Asp: OR=1.15, 95%CI=1.01-1.31, p=0.04]. In the subgroup analysis by ethnicity
      and cancer type, significantly associations were found for Caucasian populations
      [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.26, 95%CI=1.08-1.47, p<0.001; Asp/Asn vs.
      Asp/Asp: OR=1.19, 95%CI=1.02- 1.40, p=0.03] and esophageal squamous cell
      carcinoma [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.19, 95%CI=1.01-1.41, p=0.04].
      There was no heterogeneity and no publication bias existed. CONCLUSIONS: This
      meta-analysis shows that the XPD Asp312Asn polymorphism may be a risk factor for
      developing EC, especially for Caucasian populations and esophageal squamous cell
      carcinoma.

PMID- 22994752
TI  - p.R72P, PIN3 Ins16bp polymorphisms of TP53 and CCR5?32 in north Indian breast
      cancer patients.
AB  - BACKGROUND: The present study aimed to find the prognostic implications of two
      polymorphisms in TP53 (p.R72P, PIN3 Ins16bp) and one in CCR5 (CCR5/32) in
      sporadic breast cancer patients. METHODS: DNA samples of 80 breast cancer
      patients and 80 age and gender matched unrelated healthy control individuals from
      Punjab, North West India were analyzed. RESULTS: For p.R72P, the genotype
      frequency was 13.8% (RR), 58.8% (RP), 27.5% (PP) in patients and 33.9% (RR),
      40.0% (RP), 26.5% (PP) in controls. For PIN3 Ins16bp, the genotype frequencies
      were 53.75% (A1A1), 37.5% (A1A2), 8.75% (A2A2) in patients and 66.3% (A1A1),
      31.3% (A1A2), 2.5% (A2A2) in controls. Only 4 (5%) breast cancer patients were
      heterozygous for CCR5Delta32 deletion. Common RR-A1A1-WT/WT genotype was lower
      while RP-A1A2-WT/WT genotype was higher in patients as compared to controls. RP
      A1A1-WT/WT genotype was significantly higher in patients as compared to control
      individuals (p = 0.008). CONCLUSION: Though a clear association of any particular
      genotype with sporadic breast cancer or stage was not apparent, the results of
      present study were suggestive that sporadic breast cancer patients with RR-A1A1
      WT/WT genotype might have a better response to chemotherapy, thus improving their
      chances of survival.

PMID- 22994753
TI  - MicroRNA expression profile analysis reveals diagnostic biomarker for human
      prostate cancer.
AB  - Prostate cancer is a highly prevalent disease in older men of the western world.
      MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via
      posttranscriptional inhibition of protein synthesis. To identify the diagnostic
      potential of miRNAs in prostate cancer, we downloaded the miRNA expression
      profile of prostate cancer from the GEO database and analysed the differentially
      expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non
      cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the
      database and mapped to the STRING and KEGG databases for network construction and
      pathway enrichment analysis. We identified a total of 16 miRNAs that showed a
      significant differential expression in cancer samples. A total of 9 target genes
      corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment
      analysis, we finally demonstrated that miR-20 appears to play an important role
      in the regulation of prostate cancer onset. MiR-20 as single biomarker or in
      combination could be useful in the diagnosis of prostate cancer. We anticipate
      our study could provide the groundwork for further experiments.

PMID- 22994754
TI  - Relationship between the prohibitin 3' untranslated region C > T gene
      polymorphism and cancer susceptibility--results of a meta-analysis.
AB  - OBJECTIVE: The results from the published studies on the association between
      prohibitin 3' untranslated region C > T gene polymorphism and cancer risk are
      conflicting. This meta-analysis was performed to evaluate the relationship with
      cancer susceptibility overall, and to explore whether the T allele or TT genotype
      could become a predictive marker for cancer risk. METHODS: Association studies
      were identified from the databases of PubMed, Embase, and Cochrane Library as of
      March 1, 2012, and eligible investigations were synthesized using the meta
      analysis method. Results were expressed with odds ratios (OR) for dichotomous
      data, and 95% confidence intervals (CI) were also calculated. RESULTS: Six
      investigations were identified for the analysis of association between the
      prohibitin 3' untranslated region C > T gene polymorphism and cancer risk,
      covering of 1,461 patients with cancer and 1,197 controls. There was a positive
      association between the T allele and cancer susceptibility (OR=1.20, 95% CI: 1.03
      1.39, P=0.02), and CC homozygous might play a protective role (OR=0.80, 95% CI:
      0.68-6.11, P=0.95). In the sub-group analysis, prohibitin 3' untranslated region
      C > T gene polymorphism and cancer risk appeared associated with the risk of
      breast cancer, but not ovarian cancer. CONCLUSIONS: Our results indicate that T
      allele is a significant genetic molecular marker to predict cancer susceptibility
      and CC genotype is protective, especially for breast cancer. However, more
      investigations are required to further clarify the association of the prohibitin
      3' untranslated region C > T gene polymorphism with cancer susceptibility.

PMID- 22994755
TI  - Glulathione-S-transferases gene polymorphism in prediction of gastric cancer risk
      by smoking and Helicobacter pylori infection status.
AB  - AIM: To evaluate the association of glutathione S-transferases gene polymorphisms
      with the risk of gastric cancer, with reference to smoking and Helicobacter
      pylori infection. METHODS: We conducted a 1:1 matched case-control study with 410
      gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1
      and GSTP1 were determined using PCR-CTPP. RESULTS: The GSTM1 and GSTT1 null
      genotypes were significantly associated with the risk of gastric cancer after
      adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null
      GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1
      and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However,
      no association was found for GSTP1 polymorphism The smoking modified the
      association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer.
      CONCLUSION: GSTM1 and GSTT1 null genotypes are associated with increased risk of
      gastric cancer, and smoking modifies the association.

PMID- 22994756
TI  - Multicentre hospital-based case-control study of diffuse large B-cell lymphoma in
      Shanghai, China.
AB  - BACKGROUND: Several potential risk factors have been identified for diffuse large
      B-cell lymphoma (DLBCL); however, epidemiological studies investigating the
      association between these risk factors and DLBCL have yielded inconsistent
      results. OBJECTIVES: To investigate potential medical, lifestyle, and
      environmental risk factors of DLBCL in Shanghai, China through a hospital-based
      case-control study. METHOD: One-hundred- and-forty-seven newly diagnosed DLBCL
      patients and 294 sex- and age-matched controls were recruited from 11 hospitals
      in Shanghai between 2003 and 2007. A standardized structured questionnaire was
      used to obtain patient data on demographics, medical history, family history,
      lifestyle, and environmental exposures. Conditional logistic regression models
      were used to estimate odds ratios (ORs), with 95% confidence intervals (CIs), for
      risk associated with each data category. RESULTS: History of tuberculosis (TB)
      infection and "living on a farm" were positively associated with DLBCL (TB:
      OR=3.05, 95% CI: 1.19-7.80; farm: OR=1.82, 95% CI: 1.21-2.73). In contrast,
      taking traditional Chinese medicine was negatively associated with DLBCL
      (OR=0.36, 95% CI: 0.14- 0.89). No significant correlation with DLBCL risk was
      found for any of the other potential risk factors (p>0.05), including but not
      limited to hair dyes, alcohol drinking, smoking, and home/workplace renovation
      within one year. CONCLUSIONS: Consistent with results from previous studies in
      other DLBCL case populations, traditional Chinese medicine appeared to have a
      direct or indirect protective effect against DLBCL. However, this study also
      identified a possible predisposition for DLBCL in TB sufferers and farmers.

PMID- 22994757
TI  - Trend analysis of gastric cancer incidence in Iran and its six geographical areas
      during 2000-2005.
AB  - OBJECTIVE: Gastric cancer is the fourth most common cancer worldwide. While it is
      one of the most common cancers in Iran, there are only limited data regarding
      incidence trends in the country. This study is the first of its type to
      investigate trends across six geographical areas during 2000-2005 using cancer
      registry data. MATERIALS AND METHODS: The registered data for gastric cancer
      cases in National Cancer Registry System were extracted from the Ministry of
      Health and Medical Education, Center for Disease Control and Management, code
      C16. First, according to WHO population, the sex-standardized incidence rate in
      both sexes and then the trends of incidence rate during 2000-2005 were
      investigated separately for different geographical areas of the country. RESULTS:
      The incidence rates of gastric cancer in Iran and its six geographical areas
      during 2000-2005 were increasing albeit with differences in their slopes. The
      overall incidence rate increased from 2.8 in 2000 to 9.1 per 100,000 persons per
      year in 2005, rising from 4.1 to 13.2 in men. The average six-year incidence of
      gastric cancer in the central and northwestern border of Caspian Sea was 7.8 per
      100,000 persons per year, while it was 0.9 per 100,000 persons per year in the
      border of the Persian Gulf. Generally the incidence rate in men was higher than
      in women. CONCLUSION: Iran is one of the high-risk areas for gastric cancer.
      Increase in incidence might continue in the future partly because of improvement
      in cancer registry systems as well as increase in risk of this cancer.

PMID- 22994758
TI  - Anticlastogenic effect of Eryngium foetidum L. assessed by erythrocyte
      micronucleus assay.
AB  - The aim of this study was to investigate the anticlastogenicity as well as the
      clastogenicity of Eryngium foetidum leaf (EF) using the in vivo mouse peripheral
      blood erythrocyte micronucleus assay. Eighty ICR male mice were fed AIN-76 diet
      supplemented with ground freeze-dried EF at 0.0%, 0.8%, 1.6% and 3.2% for 2 weeks
      prior to the administration of both direct-acting, mitomycin C (MMC), and
      indirect-acting, 7, 12-dimethylbenz(a) anthracene (DMBA) clastogens. Peripheral
      blood samples were collected from mice just before administration of clastogen
      and at 24 and 48 h thereafter for MMC. Blood samples were collected at the same
      times and after 72 h for DMBA. Then, reticulocytes in blood samples were counted
      using fluorescent microscopy. The results indicated that EF had no clastogenic
      effect in mice. All doses of diets supplemented with EF decreased the number of
      micronucleated peripheral reticulocytes in all the MMC-treated groups in a dose
      dependent manner, but significant reduction was found only at 1.6% and 3.2% EF in
      the DMBA-treated groups. It can be concluded that EF has no clastogenicity, but
      possesses anticlastogenic potential against both direct- and indirect-acting
      types of clastogen in mice.

PMID- 22994759
TI  - Prognostically significant fusion oncogenes in Pakistani patients with adult
      acute lymphoblastic leukemia and their association with disease biology and
      outcome.
AB  - BACKGROUND AND OBJECTIVES: Chromosomal abnormalities play an important role in
      genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications.
      Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6
      RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal
      translocations and associated fusion oncogenes in adult ALL patients and study
      their relationship with clinical features and treatment outcome. METHODS: We
      studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase
      FISH at diagnosis and their association with clinical characteristics and
      treatment outcome. RESULTS: Five most common fusion genes i.e. BCR-ABL (t 9; 22),
      TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del
      1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated
      with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and
      usually presented with a platelets count of less than 50 x10(9)/l. Survival of
      patients with fusion gene ETV6-RUNX1 was better when compared to patients
      harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of
      adult ALL patients with aggressive clinical behaviour and a poor outcome.
      CONCLUSIONS: This is the first study from Pakistan which investigated the
      frequency of 5 fusion oncogenes in adult ALL patients, and their association with
      clinical features, treatment response and outcome. Frequencies of some of the
      oncogenes were different from those reported elsewhere and they appear to be
      associated with distinct clinical characteristics and treatment outcome. This
      information will help in the prognostic stratification and risk adapted
      management of adult ALL patients.

PMID- 22994760
TI  - Follow-up study of survival of patients with advanced cancer in a hospice
      setting.
AB  - OBJECTIVE: This study was to present the survival of advanced cancer patients and
      explore the influence of various factors on survival time as well as survival
      rate. The results provide guidelines for clinical practice of cancer treatment.
      METHODS: Follow-up of 674 advanced cancer patients was performed in a hospice.
      The median survival time and survival rate were calculated, and survival analysis
      was carried out. RESULTS: The median survival time of all patients dying from
      cancer was 12.0 months and the average survival time was 25.1 months. The 1-year
      cumulative survival rate was 0.518+/-0.020 and the 5-year cumulative survival
      rate was 0.088+/-0.012. The following factors showed significant impacts on
      survival rate: gender, age, primary diagnosis, surgery and the time when pain
      appeared. CONCLUSIONS: The survival time of patients with advanced cancer was
      relatively short. Major approaches to extend the survival time include early
      detection, early diagnosis, effective surgical treatment, pain control,
      reasonable supply of nutrients and multiple interventions.

PMID- 22994761
TI  - Knowledge about gastric carcinoma in North of Iran, a high prevalent region for
      gastric carcinoma: a population-based telephone survey.
AB  - BACKGROUND AND OBJECTIVES: The most northern and northwestern regions of Iran are
      at a high risk for gastric cancer. The aim of this study was to assess the
      general population's awareness about risk factors, symptoms and signs, preventive
      methods and management of gastric carcinoma in a high prevalence city in the
      North of Iran. METHODS: A cross-sectional population-based telephone survey which
      was conducted on 3,457 residents of Rasht, the capital city of Guilan Province,
      to assess their awareness regarding gastric carcinoma. The questionnaires
      contained demographic data and statements on respondents' knowledge about risk
      factors, symptoms and signs, prevention and management of gastric cancer which
      were filled by general practitioners after asking the subjects. Data were
      analyzed in SPSS14. P<0.05 was considered significant. RESULTS: The mean
      knowledge score of the respondents was 5.05+/-1.37 regarding risk factors of
      gastric carcinoma, 4.39+/-1.99 regarding symptoms and signs, 6.0+/-1.22 regarding
      preventive strategies, and 1.6+/-1.16 regarding management. Totally the mean
      knowledge level of the respondents toward gastric carcinoma would be 17.1+/-3.97
      from the maximum grade of 29. The age group of 45-55 y/o, bachelor degree and
      higher, physicians and nurses, those who had cancer history in friends or had the
      history of gastrointestinal diseases showed significantly higher knowledge scores
      (P=0.001). CONCLUSION: There is a general lack of awareness of cancer risk
      factors, symptoms and signs, methods of prevention, and importance of early
      diagnosis and treatment. Educational programs should be developed to promote
      adherence to recommended screening guidelines.

PMID- 22994762
TI  - HDAC6 siRNA inhibits proliferation and induces apoptosis of HeLa cells and its
      related molecular mechanism.
AB  - OBJECTIVE: To investigate the effects of histone deacetylase 6 (HDAC6) siRNA on
      cell proliferation and cell apoptosis of the HeLa cervical carcinoma cell line
      and the molecular mechanisms involved. METHODS: Division was into three groups:
      A, the untreated group; B, the control siRNA group; and C, the HDAC6 siRNA group.
      Lipofectamine 2000 was used for siRNA transfection, and Western blot analysis was
      used to determine the protein levels. Cell proliferation and apoptosis were
      characterized using a CCK-8 assay and flow cytometry, respectively. RESULTS:
      HDAC6 protein expression in the HDAC6 siRNA-transfection group was significantly
      lower (P < 0.05) than in the untreated and control siRNA groups. The CCK-8 kit
      results demonstrated that the proliferation of HeLa cells was clearly inhibited
      in the HDAC6 siRNA transfection group (P < 0.05). In addition, flow cytometry
      revealed that the early apoptotic rate (26.0% +/- 0.87%) was significantly
      elevated (P < 0.05) as compared with the untreated group (10.6% +/- 1.19%) and
      control siRNA group (8.61% +/- 0.98%). Furthermore, Western blot analysis
      indicated that bcl-2 protein expression in the HDAC6 siRNA-transfection group was
      down-regulated, whereas the expression of p21 and bax was up-regulated.
      CONCLUSION: HDAC6 plays an essential role in the occurrence and development of
      cervical carcinoma, and the down-regulation of HDAC6 expression may be useful
      molecular therapeutic method.

PMID- 22994763
TI  - Head and neck squamous cell carcinoma in Iranian patients and risk factors in
      young adults: a fifteen-year study.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 8th most common
      cancer worldwide. Although older age, male gender, smoking and alcohol
      consumption are known risk factors, an increasing number of HNSCC patients are
      without typical risk factors. Our aim was to define demographics of HNSCC in Iran
      and the potential risk factors related to Iranian ethnicity and lifestyle.
      METHODS: We conducted a cross-sectional analytical study on 262 patients with
      primary SCC of the larynx, hypopharynx or tongue referred to our pathology
      department during 1995-2010. Patients' demographics, tumor characteristics and
      risk factors such as smoking, alcohol consumption and anemia were analyzed and
      compared in two groups of patients: over 40 years (older group) and 40 years or
      less (young group); Chi-square and Mann-Whitney analytical tests were employed.
      RESULTS: 5.7% of patients were young adults. The male to female ratio was 1.5 in
      the younger group and 5.6 in the older group. In young adults, 40% of tumors were
      located in larynx and 40% in the tongue. Age >40 was significantly associated
      with laryngeal location (P<0.001). History of smoking and drinking was
      significantly associated with age >40 and SCC of larynx in both age groups.
      Cervical lymph node involvement was significantly correlated with SCC of tongue
      (P<0.001), however, considering young adults only, SCC of hypopharynx was most
      frequently accompanied by lymph node involvement (60%). The most prevalent tumor
      among men was SCC of larynx whereas SCC of hypopharynx was the most prevalent
      tumor among women (61%), of whom 18.2% were <=40. CONCLUSIONS: The incidence of
      HNSCC among young adults seems to be higher in Iran compared to other countries.
      Reduction in exposure to known risk factors, especially tobacco smoking in forms
      of cigarettes and bubble pipes, and search for other causative agents of HNSCC in
      young population is recommended.

PMID- 22994764
TI  - Relationships of uPA and VEGF expression in esophageal cancer and microvascular
      density with tumorous invasion and metastasis.
AB  - OBJECTIVE: To investigate uPA and VEGF expression in esophageal cancer and
      relations with tumorous invasion and metastasis. METHODS: Immunohistochemistry
      was used to detect uPA and VEGF expression in the normal epithelial tissue of
      esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and
      analyze the relationships with clinical pathological features and tumor
      angiogenesis. RESULTS: Positive rates for uPA and VEGF protein expression were
      significantly greater in esophageal cancer than normal epithelial tissue (P <
      0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein
      expression of the high microvessel density (MVD) group was significantly lower
      than in the low MVD group (P < 0.05), with relation to clinical pathological
      staging, differentiation and lymph node metastasis (P < 0.05). CONCLUSION: In
      esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote
      tumor angiogenesis, indicative of a poor prognosis.

PMID- 22994765
TI  - Assessment of biochemical profiles in premenopausal and postmenopausal women with
      breast cancer.
AB  - OBJECTIVE: The study was conducted to assess biochemical profiles in
      premenopausal and postmenopausal women having breast cancer. MATERIALS AND
      METHODS: A hospital based case control study was carried out at Manipal Teaching
      Hospital (MTH), Pokhara, Nepal. The analysed variables were age, metabolic
      profile including total cholesterol, triglycerides, HDL-C, LDL-C, blood sugar,
      insulin concentration, C-peptide, HbA1c and selenium. Descriptive statistics and
      testing of hypothesis were used for the analysis using EPI INFO and SPSS 16
      software. RESULTS: In premenopausal women, significant differences were noted for
      total cholesterol (P value <0.001), triglycerides (P value 0.002), HbA1c level (P
      value <0.001), insulin concentration (P value 0.030), C-peptide concentration (P
      value 0.001), and selenium (P value <0.001) between cases and controls.
      Insignificant results were found for HDL-C (P value 0.749), LDL-C (P value
      0.933), blood sugar (P value 0.59) and BMI (P value 0.746). Similarly,
      significant difference in total cholesterol (P value <0.001), triglycerides (P
      value 0.001), LDL-C (P value <0.001), HDL-C (P value 0.025), blood sugar (P value
      <0.001), insulin concentration (P value <0.001), c-peptide concentration (P value
      <0.001), HbA1c level (P value <0.001) and selenium (P value <0.001) were observed
      for postmenopausal patients and controls. CONCLUSIONS: Assessing metabolic
      changes and their management may be important for control of breast cancer and
      increased survival.

PMID- 22994766
TI  - Meta analysis of studies about breast self examination between 2000-2009 in
      Turkey.
AB  - AIM: The aim of this study was to analyze studies in Turkey about self-breast
      examination and produce conclusive, reliable and detailed basis for future
      studies. METHODS: Studies performed between 2000 and 2009 (until the end of
      September) were retrieved from databases using breast cancer, breast examination,
      breast cancer screening and risk factors as key words. Fifty-nine studies were
      identified and 18 of them (15 journal articles and three theses) were used for
      the meta-analysis t. RESULTS: Married women and women with a family history of
      breast cancer were found to perform self-breast examination more frequently than
      single women and women without a family history of breast cancer, respectively
      (OR=1.02 %CI 0.82-1.63; OR=1.16 %CI 0.82-1.63). According to the health belief
      model scales, women performing self-breast examination were determined to have
      1.7 times higher susceptibility (OR=1.70), 1.34 times higher seriousness
      perception (OR=1.34), 3.32 times higher health motivation (OR=3.32), 5.21 times
      more self-efficacy/confidence (OR=5.21) and 2.56 times higher self-breast
      examination benefit perception (OR=2.56). CONCLUSION: Nursing care models caused
      an increase in self-breast examination by women, and thus, it may be useful to
      organize and evaluate such health-related programs and consider women health
      perceptions.

PMID- 22994767
TI  - Prevalence of OV infection in Yasothon Province, Northeast Thailand.
AB  - A liver fluke, Opisthorchis viverrrini (OV), is the major cause of the high
      incidence of cholangiocarcinoma in Thailand. The prevalence of OV infection
      remains high in various parts of the country, especially in Northeast Thailand
      and particularly in wetland rural areas where a large proportion of the community
      work in agriculture and continue the traditional practice of eating raw or
      undercooked cyprinoid fish products. The national control program seems to have
      had little impact in many of these areas, and it has been difficult to make
      precise assessments of the overall effectiveness of the program. This paper is
      the first report of prospective research project designed to monitor the impact
      of the national control program in rural communities located in a northeastern
      province and at high risk of OV infection. The participants in this initial
      survey were 1,569 villagers, aged 20-65 years, living in two subdistricts of
      Yasothon Province. Stool examinations showed that 38.68% were infected with OV.
      Males were slightly more likely to be infected than females, but the difference
      was not statistically significant. Infection was found to be positively
      associated with age in both males and females. The preliminary data indicate that
      the population selected for study is suitable for the purpose of the monitoring
      project.

PMID- 22994768
TI  - RALY RNA binding protein-like reduced expression is associated with poor
      prognosis in clear cell renal cell carcinoma.
AB  - The molecular mechanisms involved in the progression of clear cell renal cell
      carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the
      relationships between expression of RALYL and clinical characteristics. In 41
      paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to
      evaluate the expression of RALYL mRNA. RALYL protein levels were determined in
      146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry.
      Statistical analysis was used to explore the relationships between expression of
      RALYL and the clinical characteristics (gender, age, tumor size, T stage, N
      stage, M stage, survival times and survival outcome) in ccRCC. In addition, these
      patients were follow-up period 64 months (range: 4~116 months) to investigate the
      influence on prognosis. We found significantly differences between ccRCC tissues
      and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL.
      Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues
      showed significantly lower RALYL protein levels in ccRCC samples (chi2-test,
      p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N
      stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender
      (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower
      level of RALYL expression had a poorer survival rate than those with a higher
      level of RALYL expression, significantly different by the log-rank test
      (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N
      stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis
      factors for the overall survival of ccRCC patients. We demonstrated that the
      expression of RALYL was significantly low in ccRCC and correlated with a poor
      prognosis in a large number of clinical samples. Our findings showed that RALYL
      may be a potential therapeutic target as well as a poor prognostic factor.

PMID- 22994769
TI  - CYP1A1 gene polymorphisms: modulator of genetic damage in coal-tar workers.
AB  - AIM: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo
      (a) pyrene have carcinogenic properties and may cause many types of cancers in
      human populations. Genetic susceptibility might be due to variation in genes
      encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450).
      Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1
      and m2) on genetic damage in 115 coal-tar workers exposed to PAHs in their work
      place. METHODS: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP
      method. Comet and buccal micronucleus assays were used to evaluate genetic damage
      among 115 coal tar workers and 105 control subjects. RESULTS: Both CYP1A1 m1 and
      CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well
      as synergistically showed significant association (P<0.05) with genetic damage as
      measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control
      and exposed subjects. CONCLUSION: In our study we found significant association
      of CYP1A1 m1 and m2 heterozygous (wt/mt) +homozygous (mt/mt) variants with
      genetic damage suggesting that these polymorphisms may modulate the effects of
      PAH exposure in occupational settings.

PMID- 22994770
TI  - Lack of association between LIG4 gene polymorphisms and the risk of breast
      cancer: a HuGE review and meta-analysis.
AB  - OBJECTIVE: Non-homologous end joining (NHEJ) is one of the pathways of repair of
      DNA double-strand breaks. A number of genes involved in NHEJ have been implicated
      as breast cancer susceptibility genes such as LIG4. However, some studies have
      generated conflicting results. The aim of this Human Genome Epidemiology (HuGE)
      review and meta-analysis was to investigate association between LIG4 gene
      polymorphisms in the NHEJ pathway and breast cancer risk. METHODS: Studies
      focusing on the relationship between LIG4 gene polymorphisms and susceptibility
      to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of
      Science, Springerlink, CNKI and CBM databases. Data were extracted by two
      independent reviewers and the meta-analysis was performed with Review Manager
      Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with
      95% confidence intervals (95%CIs). RESULTS: According to the inclusion criteria,
      we final included seven studies with a total of 10,321 breast cancer cases and
      10,160 healthy controls in the meta-analysis. The results showed no association
      between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and
      rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of
      these SNPs neither increased nor decreased the risk for breast cancer. In the
      subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also
      found no associations between the variants of LIG4 gene and breast cancer risk
      among HWE, non-HWE, Caucasians, Asians and Africans. CONCLUSION: This meta
      analysis suggests that there is a lack of any association between LIG4 gene
      polymorphisms and the risk of breast cancer.

PMID- 22994771
TI  - Rapid detection of ovarian cancer from immunized serum using a quartz crystal
      microbalance immunosensor.
AB  - BACKGROUND: The objective of this study was to measure the antibody content of
      NuTu-19 ovarian cancer cells in serum samples using a quartz crystal microbalance
      (QCM) immunosensor. MATERIALS AND METHODS: NuTu-19 cells were first cultured onto
      the electrode surfaces of crystals in Dulbecco's modified Eagle medium, and then
      specified amounts of immunized serum samples of immunized rabbit were also added.
      The change in mass caused by specific adsorbtion of antibodies of NuTu-19 to the
      surfaces of the crystals was detected. RESULTS: The change in resonance frequency
      of crystals caused by immobilization of NuTu-19 cells was from 83 to 429 Hz. The
      antibody content of NuTu-19 detected was 341 ng/ul. The frequency shifts were
      linearly dependent on the amount of antibody mass in the range of 69 to 340 ng.
      The positive detection rate and the negative detection rate were 80% and 100%,
      respectively. CONCLUSION: This immunoassay provides a viable alternative to other
      early ovarian cancer detection methods and is particularly suited for health
      screening of the general population.

PMID- 22994772
TI  - TNM stages and prognostic features of colorectal mucinous adenocarcinomas: a meta
      analysis.
AB  - AIM: The significance of the mucinous adenocarcinoma in TNM staging and prognosis
      for colorectal tumor patients is still controversial. The aim was to provide a
      meta-analysis for TNM staging and prognostic features of colorectal tumors.
      METHODS: 30 individual case-control studies were finally included into this meta
      analysis, involving a total of 444,489 cancer cases and 45,050 mucinous
      adenocarcinomas, of relations with TNM staging and prognostic features. RESULTS:
      Compared to non-mucinous adenocarcinoma patients, the TNM IV stage accounted for
      a larger percentage of mucinous adenocarcinomas (OR=1.48, 95%CI 1.28-1.71,
      POR<0.001) and the prognosis was significantly poor (HR=1.06, 95%CI 1.04-1.08,
      P<0.001). After heterogeneity testing, the results was similar to the holistic
      approach outcome (HR=1.48, 95%CI 1.35-1.62, P<0.001). CONCLUSION: Compared to
      patients with non-mucinous adenocarcinomas, mucinous adenocarcinoma patients with
      later TNM staging make up a big percentage, and mucinous adenocarcinoma is an
      independent risk factor for poor prognosis.

PMID- 22994773
TI  - Association of functional polymorphisms of the XRCC4 gene with the risk of breast
      cancer: a meta-analysis.
AB  - OBJECTIVE: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for
      DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway.
      Several potentially functional polymorphisms of the XRCC4 gene have been
      implicated in breast cancer risk, but individually published studies showed
      inconclusive results. The aim of this meta-analysis was to investigate the
      association between XRCC4 polymorphisms and the risk of breast cancer. METHODS:
      The MEDLINE, EMBASE, Web of science and CBM databases were searched for all
      relevant articles published up to June 20, 2012. Potential associations were
      assessed with comparisons of the total mutation rate (TMR), complete mutation
      rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical
      analyses were performed using RevMan 5.1.6 and STATA 12.0 software. RESULTS: Five
      studies were included with a total of 5,165 breast cancer cases and 4,839 healthy
      controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and
      rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast
      cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of
      breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del)
      and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an
      influence on breast cancer susceptibility. CONCLUSION: Results from the current
      meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms
      of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685
      (G>T) and rs10057194 (A>G) might be protective factors.

PMID- 22994774
TI  - The clinicopathological significance of Bmi-1 expression in pathogenesis and
      progression of gastric carcinomas.
AB  - BACKGROUND: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion
      region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an
      important role in the regulation of proliferation, senescence, cell cycle and
      apoptosis, chromosome stability, activation of gene transcription. METHODS: To
      clarify the roles of Bmi-1 in tumourigenesis and progression of gastric
      carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in
      gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a
      comparison of its expression with clinicopathological parameters of carcinomas.
      RESULTS: There was gradually increased Bmi-1 protein expression from gastritis,
      IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to
      tumor size, depth of invasion, lymph node metastasis and worse prognosis of
      carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There
      was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse
      type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from
      gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was
      observed in gastric carcinoma with larger diameter, deeper invasion, lymph node
      metastasis, and intestinal-type carcinoma (p<0.05). CONCLUSION: These findings
      indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis,
      growth, invasion, metastasis and differentiation of gastric carcinomas. It was
      considered as a promising marker to indicate the aggressive behaviors and
      prognosis of gastric carcinomas.

PMID- 22994775
TI  - Predictors of breast cancer screening uptake: a pre intervention community survey
      in Malaysia.
AB  - INTRODUCTION: Despite health education efforts to educate women on breast cancer
      and breast cancer screening modalities, the incidence of breast cancer and
      presentation at an advanced stage are still a problem in Malaysia. OBJECTIVES: To
      determine factors associated with the uptake of breast cancer screening among
      women in the general population. METHODS: This pre-intervention survey was
      conducted in a suburban district. All households were approached and women aged
      20 to 60 years old were interviewed with pre-tested guided questionnaires.
      Variables collected included socio-demographic characteristics, knowledge on
      breast cancer and screening practice of breast cancer. Univariate and
      multivariate analysis were performed. RESULTS: 41.5% of a total of 381
      respondents scored above average; the mean knowledge score on causes and risks
      factors of breast cancer was 3.41 out of 5 (SD1.609). 58.5% had ever practiced
      BSE with 32.5% performing it at regular monthly intervals. Uptake of CBE by
      nurses and by doctors was 40.7% and 37.3%, respectively. Mammogram uptake was
      14.6%. Significant predictors of BSE were good knowledge of breast cancer
      (OR=2.654, 95% CI: 1.033-6.816), being married (OR=2.213, 95% CI: 1.201-4.076)
      and attending CBE (OR=1.729, 95% CI: 1.122-2.665). Significant predictors for CBE
      included being married (OR=2.161, 95% CI: 1.174-3.979), good knowledge of breast
      cancer (OR=2.286, 95% CI: 1.012-5.161), and social support for breast cancer
      screening (OR=2.312, 95% CI: 1.245-4.293). Women who had CBE were more likely to
      undergo mammographic screening of the breast (OR=5.744, 95% CI: 2.112-15.623),
      p<0.005. CONCLUSION: CBE attendance is a strong factor in promoting BSE and
      mammography, educating women on the importance of breast cancer screening and on
      how to conduct BSE. The currently opportunistic conduct of CBE should be extended
      to active calling of women for CBE.

PMID- 22994776
TI  - Survival rate and prognostic factors of esophageal cancer in east Azerbaijan
      province, North-west of Iran.
AB  - BACKGROUND: Esophageal cancer in Iran is the sixth most common cancer and is
      particularly important in east Azerbaijan. The aim of this study was to calculate
      survival rates and define prognostic factors in esophageal cancer patients.
      METHODS: In this study, all patients with esophageal cancer registered in the
      Radiation Therapy Center, during March 2006 to March 2011, were analyzed and
      followed up for vital status. Data were analyzed using the Kaplan-Meier method
      and the Cox proportional hazard models. RESULTS: Out of 532 patients, survival
      information was available for 460, including 205 (44/5%) females and 255 (55/4%)
      males. The mean age was 65.8+/-12.2, ranging from 29 to 90 years at the time of
      diagnosis. 1- , 3- and 5-year survival rates after diagnosis were 55%, 18% and
      12%, respectively, with a median survival time of 13.2 +/- .7 (CI 95%=11.8-14.6)
      months. In the univariate analysis, age (P=0/001), education (P=0/001), smoking
      status (P= 0/001), surgery (P=0/001), tumor differentiation (P=0/003) and tumor
      stage (P=0/001) were significant prognostic factors. Tumor morphology, sex, place
      of residence, tumor histology and tumor location did not show any significant
      effects on the survival rate. In multivariate analysis, age (P=0/003), smoking
      (P=0/01) and tumor stage (P=0/001) were significant independent predictors of
      survival. CONCLUSION: In summary, prognosis of esophageal cancer in North West of
      Iran is poor. Therefore, reduction in exposure to risk factors and early
      detection should be emphasized to improve survival.

PMID- 22994777
TI  - Follow up of atypical squamous cell Pap smears in Iraqi women.
AB  - OBJECTIVES: To report the prevalence of atypical squamous cells of undetermined
      significance and atypical squamous cells-cannot exclude high squamous
      intraepithelial lesion and to determine the possible association of Pap test
      results with high-risk human papillomavirus and high squamous intraepithelial
      lesions in women from Duhok, Iraq. DESIGN: A prospective, observational study was
      conducted between January 2005 and December 2011. Overall, 596 women with a
      cervicovaginal Pap test showing atypical squamous cells of undetermined
      significance and 93 atypical squamous cells-cannot exclude high squamous
      intraepithelial lesion for whom pathologic follow-up was available were studied.
      Follow-up consisted of repeat cytology, colposcopy and histology. High risk human
      papillomavirus DNA testing was performed on exfoliated cervical cells from 106
      women, using conventional PCR after at least 36 months from the initial Pap
      smear. RESULTS: Significantly high proportions of both atypical squamous cells of
      undetermined significance (87.9%) and atypical squamous cells-cannot exclude high
      squamous intraepithelial lesion (62.4%) demonstrated no significant lesion on
      subsequent follow up. Low squamous intraepithelial lesions were observed in 1.7%
      of cases of atypical squamous cells of undetermined significance and in 5.4% of
      atypical squamous cells-cannot exclude high squamous intraepithelial lesion. High
      squamous intraepithelial lesion was demonstrated in 0.8% and 16.1% respectively.
      In the latter there was also one case of invasive carcinoma. High-risk HPV DNA
      was demonstrated in 40% of atypical squamous cells of undetermined significance
      and 57.1% of atypical squamous cells-cannot exclude high squamous intraepithelial
      lesions. CONCLUSIONS: Since both atypical squamous cells of undetermined
      significance and atypical squamous cells-cannot exclude high squamous
      intraepithelial lesion identify patients who are at an increased risk for the
      development of high squamous intraepithelial lesions and a considerable
      percentage harbor high risk-HPV, both should be retained as diagnostic categories
      and patients warrant a diligent follow up and testing for high risk-HPV DNA.
      Colposcopic evaluation and biopsy, when indicated, are a must.

PMID- 22994778
TI  - Association between polymorphisms of dihydrofolate reductase and gamma glutamyl
      hydrolase genes and toxicity of high dose methotrexate in children with acute
      lymphoblastic leukemia.
AB  - Methotrexate (MTX) is an important drug for the treatment of childhood acute
      lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs
      which may cause interruption of treatment, morbidity, and mortality. Single
      nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma
      glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus
      affect the metabolism of MTX and influence the effectiveness. Therefore, we
      hypothesized that genetic variations of DHFR and GGH genes may influence the risk
      of toxicity after high dose MTX. The study population comprised of 105 children
      with ALL who were treated according to the modified St Jude Total XV protocol.
      The patients received 2.5 or 5 g/m2 of MTX for 5 doses during the consolidation
      phase. Genotyping of DHFR 829C>T and GGH -401C>T was performed using a polymerase
      chain reaction- restriction fragment length polymorphism (PCR-RFLP). The GGH
      401CT and TT genotypes were associated with increased risk of leukopenia and
      thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02,
      95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion,
      the GGH -401CT and TT genotypes were found to increase the risk of severe
      leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL
      therapy.

PMID- 22994779
TI  - GSTP1, ERCC1 and ERCC2 polymorphisms, expression and clinical outcome of
      oxaliplatin-based adjuvant chemotherapy in colorectal cancer in Chinese
      population.
AB  - AIM: Platinum agents have shown to be effective in the treatment of colorectal
      cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1,
      ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in
      patients receiving oxaliplatin-based chemotherapy in a Chinese population.
      METHODS: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal
      cancer patients were assessed using TaqMan nuclease assays. RESULTS: At the time
      of final analysis on Nov. 2011, the median follow-up period was 37.7 months
      (range from 1 to 60 months). A total of 229 patients died during follow-up. Our
      study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95%
      CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly
      associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C
      and ERCC2 G/G were also related to longer survival among patients with colon
      cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16
      0.91), respectively. CONCLUSION: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2
      Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for
      colorectal cancer patients.

PMID- 22994780
TI  - Histone deacetylase inhibitor trichostatin A enhances anti-tumor effects of
      docetaxel or erlotinib in A549 cell line.
AB  - BACKGROUND AND OBJECTIVE: Histone deacetylase (HDAC) inhibitors represent a
      promising class of potential anticancer agents for treatment of human
      malignancies. In this study, we investigated the effect of trichostatin A (TSA),
      one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic
      chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung
      cancer A549 cells. METHODS: A549 cells were treated with TXT, erlotinib alone or
      in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle
      distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5
      diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry.
      Moreover, immunofluorescent staining and Western blot analysis were employed to
      examine alterations of alpha-tubulin, heat shock protein 90 (hsp90), epidermal
      growth factor receptor (EGFR), and caspase-3 in response to the different
      exogenous stimuli. RESULTS: Compared with single-agent treatment, co-treatment of
      A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell
      proliferation, induced apoptosis, and caused cell cycle delay at the G2/M
      transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase
      of cleaved caspase-3 expression, also resulting in elevated acetylation of alpha
      tubulin or hsp90 and decreased expression of EGFR, which was negatively
      associated with the level of acetylated hsp90. CONCLUSIONS: Synergistic anti
      tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells.
      Such combinations may provide a more effective strategy for treating human lung
      cancer.

PMID- 22994781
TI  - Oxaliplatin sensitizes OS cells to TRAIL-induced apoptosis via down-regulation of
      Mcl1.
AB  - PURPOSE: To investigate the killing effect on OS cells of a combination of
      oxaliplatin and TRAIL and related molecular mechanisms. METHODS: TRAIL and
      oxaliplatin were applied to OS732 cells singly or jointly and survival inhibition
      rates were measured by MTT assay, changes of cellular shape being assessed with
      inverted phase contrast and fluorescence microscopy. Apoptotic rates were
      analyzed by flow cytometry (FCM) and immunocytochemistry was used to examine Mcl1
      expression of OS732 cells. RESULTS: The survival inhibition rate of combined
      application of 100 MUg/ml TRAIL and 1 MUg/ml oxaliplatin on OS-732 cells was
      significantly higher than that of either agent singly (p<0.01). Changes of
      cellular shape and apoptotic rates also indicated apoptosis-inducing effects of
      combined application to be much stronger than those of individual application.
      Oxaliplatin had the effect of down-regulating Mcl1 expression and sensitizing OS
      cells to TRAIL-induced apoptosis. CONCLUSION: A combination of TRAIL and
      oxaliplatin exerts strong killing effects on OS-732 cells which might be related
      to down-regulation of Mcl1 expression.

PMID- 22994782
TI  - TERT rs2736098 polymorphism and cancer risk: results of a meta-analysis.
AB  - OBJECTIVE: Several studies have demonstrated associations between the TERT
      rs2736098 single nucleotide polymorphisms (SNPs) and susceptibility to cancer
      development. However, there are conflicting results. A systematic meta-analysis
      was therefore performed to establish the cancer risk associated with the
      polymorphism. METHODS: In this meta-analysis, a total of 6 case-control studies,
      including 5,567 cases and 6,191 controls, were included. Crude odds ratios with
      95% confidence intervals were used to assess the strength of associations in
      several genetic models. RESULTS: Our results showed no association reaching the
      level of statistical significance for overall risk. Interestingly, in the
      stratified analyses (subdivided by ethnicity), significantly increased risks were
      found in the Asian subgroup which indicates the TERT rs2736098 polymorphism may
      have controversial involvement in cancer susceptibility. CONCLUSIONS: Overall,
      this meta-analysis indicates that the TERT rs2736098 polymorphism may have little
      involvement in cancer susceptibility.

PMID- 22994783
TI  - Hypermethylation of suppressor of cytokine signaling 1 in hepatocellular
      carcinoma patients.
AB  - Hepatocellular carcinoma (HCC), the most common primary hepatic tumor, is highly
      prevalent in the Asia-Pacific region, including Thailand. Many genetic and
      epigenetic alterations in HCC have been elucidated. The aim of this study was to
      determine whether aberrant methylation of the suppressor of cytokine signaling 1
      gene (SOCS1) occurs in HCCs. Methylation specific-PCR assays were performed to
      identify the methylation status of SOCS1 in 29 tumors and their corresponding
      normal liver tissues. An abnormal methylation status was detected in 17 (59%),
      with a higher prevalence of aberrant SOCS1 methylation significantly correlating
      with HCC treated without chemotherapy (OR=0.04, 95%CI=0.01-0.31; P=0.001). This
      study suggests that epigenetic aberrant SOCS1 methylation may be a predictive
      marker for HCC patients.

PMID- 22994784
TI  - Diagnostic value of interleukin 21 and carcinoembryonic antigen levels in
      malignant pleural effusions.
AB  - The aim of this study was to evaluate the diagnostic value of interleukin 21 (IL
      21) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions (TPEs)
      and malignant pleural effusions (MPEs). Pleural effusion samples from 103
      patients were classified on the basis of diagnosis as TPE (n=51) and MPE (n=52).
      The concentration of IL-21 was determined by ELISA. Lactate dehydrogenase (LDH),
      adenosine dehydrogenase (ADA) and CEA levels were also determined in all
      patients. A significant difference was observed in the levels of ADA and CEA
      (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The
      concentration of IL-21 in MPE was significantly higher compared to TPE (P<0.01).
      With a threshold value of 4.32 pg/ml, IL-21 had a sensitivity of 76.9% (40/52)
      and a specificity of 80.4% (41/51). Combined detection of IL-21 and CEA had a
      sensitivity of 69.2% (36/52) and a specificity of 92.2% (47/51). These two
      markers can contribute to the differential diagnosis of MPEs.

PMID- 22994785
TI  - CHEK2 1100delC variant and breast cancer risk in Caucasians: a meta-analysis
      based on 25 studies with 29,154 cases and 37,064 controls.
AB  - Links between the CHEK2 1100delC heterozygote and breast cancer risk have been
      extensively explored. However, both positive and negative associations with this
      variant have been reported in individual studies. For a detailed assessment of
      the CHEK2 1100delC heterozygote and breast cancer risk, relevant studies
      published as recently as May 2012 were identified using PUBMED and EMBASE and
      selected using a priori defined criteria. The strength of the relationship
      between the CHEK2 1100delC variant and breast cancer risks was assessed by odds
      ratios (ORs) under the fixed effects model. A total of 29,154 cases and 37,064
      controls from 25 case-control studies were identified in this meta-analysis. The
      CHEK2 1100delC heterozygote was more frequently detected in cases than in
      controls (1.34% versus 0.44%). A significant association was found between CHEK2
      1100delC heterozygote and breast cancer risk (OR=2.75, 95% CI: [2.25, 3.36]). The
      ORs and CIs were 2.33 (95% CI: [1.79, 3.05]), 3.72 (95% CI: [2.61, 5.31]) and
      2.78 (95% CI: [2.28, 3.39]) respectively in unselected, family, early-onset
      breast cancer subgroups. The CHEK2 1100delC variant could be a potential factor
      for increased breast cancer risk in Caucasians. However, more consideration is
      needed in order to apply it to allele screening or other clinical work.

PMID- 22994786
TI  - Silencing of lysyl oxidase gene expression by RNA interference suppresses
      metastasis of breast cancer.
AB  - OBJECTIVE: The aim of this study was to investigate possible mechanisms of LOX
      gene effects on invasion and metastasis of breast cancer cells by RNA
      interference. METHODS: LOX-RNAi-LV was designed, synthesized, and then
      transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2
      and MMP-9 was determined by real-time PCR, and protein expression of LOX by
      Western blotting. Cell migration and invasiveness were assessed with Transwell
      chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal
      breast tissues, and 20 cases of benign lesion tissues were assessed by
      immunohistochemistry. RESULTS: Expression of LOX mRNA and protein was suppressed,
      and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group
      than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB
      231 cells. Migration and invasion abilities were obviously inhibited. The
      expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues
      and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20),
      respectively, associations being noted with clinical stage, lymph node
      metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively
      correlated with MMP-2 and MMP-9. CONCLUSION: LOX displayed an important role in
      invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression
      which probably exerted synergistic effects on the extracellular matrix (ECM).

PMID- 22994787
TI  - Influence of alcohol consumption on oxidative stress and antioxidant status in
      cancer patients--case-control study from Western Nepal.
AB  - AIM: The present study assess the effect of consumption of alcohol on oxidative
      stress and antioxidant status in patients suffering from different types of
      cancer. METHODS: This hospital based case control study conducted in the Western
      part of Nepal covered a total of 93 cancer patients with or without alcohol
      intake and smoking habits, along with 94 age, sex and habit-matched individuals
      serving as controls. Plasma thiobarbituric acid reacting substances (TBARS),
      total antioxidant activity (TAA), vitamin C, alpha-tocopherol and erythrocyte
      reduced glutathione (GSH) were estimated and compared. RESULTS: The TBARS level
      was found to be significantly higher (p<=0.001) in all types of cancer patients
      when compared to controls, being aggravated in alcoholics with a smoking habit.
      No statistical significance (p>=0.05) was observed in the level of vitamin C and
      alpha-tocopherol. GSH and TAA level were significantly decreased (p<=0.001) in
      all the groups except those who consumed both branded as well as homemade alcohol
      and non-alcoholics without smoking habit. CONCLUSION: Alcohol, irrespective of
      its commercial brand, increases oxidative stress in all types of cancer patients.
      This is even higher when alcohol intake is combined with a smoking habit.
      Decreased TAA and GSH are major risk factors for cancer development.

PMID- 22994788
TI  - Anti-metastatic effects on B16F10 melanoma cells of extracts and two prenylated
      xanthones isolated from Maclura amboinensis Bl roots.
AB  - Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for
      the treatment of cancers, on metastatic potential of highly metastatic B16F10
      melanoma cells were investigated in vitro. Cell proliferation was assessed using
      the MTT colorimetric assay. Details of metastatic capabilities including
      invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden
      Chamber invasion and migration, scratch motility and cell attachment assays,
      respectively. The results demonstrated that n-hexane and chloroform extracts
      exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and
      aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity
      guided chromatographic fractionation of both active n-hexane and chloroform
      extracts led to the isolation of two main prenylated xanthones and
      characterization as macluraxanthone and gerontoxanthone-I, respectively, their
      structures being identified by comparison with the spectral data. Interestingly,
      both exhibited potent effective effects. At non-toxic effective doses, n-hexane
      and chloroform extracts (10 and 30 MUg/ml) as well as macluraxanthone and
      gerontoxanthone-I (3 and 10 MUM) significantly inhibited B16F10 cell invasion, to
      a greater extent than 10 MUM doxorubicin, while reducing migration of cancer
      cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells
      to high concentrations of chloroform (30 MUg/ml) and geratoxanthone-I (20 MUM)
      for 24 h resulted in delayed adhesion and retarded colonization. As insights into
      mechanisms of action, typical morphological changes of apoptotic cells e.g.
      membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic
      bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with
      increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow
      cytometry were observed, suggesting DNA damage and subsequent apoptotic cell
      death. Taken together, our findings indicate for the first time that active n
      hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I
      isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis
      processes including proliferation, adhesion, invasion and migration, possibly
      through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based
      on these data, M. amboinensis Bl. represents a potential candidate novel
      chemopreventive and/or chemotherapeutic agent. Additionally, they also support
      its ethno-medicinal usage for cancer prevention and/or chemotherapy.

PMID- 22994789
TI  - Combined screening of cervical cancer, breast cancer and reproductive tract
      infections in rural China.
AB  - OBJECTIVES: To investigate the current prevalence and knowledge of cervical
      cancer, breast cancer and reproductive tract infections (RTIs) in rural Chinese
      women, and to explore the acceptance and feasibility of implementing a combined
      screening program in rural China. METHODS: A population-based, cross-sectional
      study was conducted among women aged 30 to 59 years old in Xiangyuan County,
      Shanxi Province from 2009 to 2010. Socio-demographic characteristics, knowledge
      of cervical cancer, breast cancer and RTIs, and the attitude toward single or
      combined screening were collected by an interview questionnaire. Each participant
      received a clinical examination of the cervix, breast and reproductive tract.
      Examinations included visual inspection, mammography, laboratory tests and
      pathological diagnosis. RESULTS: A total of 1,530 women were enrolled in this
      study. The prevalence of cervical precancerous lesions, suspicious breast cancer,
      suspicious benign breast disease and RTIs was 1.4%, 0.2%, 14.0% and 54.3%,
      respectively. Cervicitis, trichomonas vaginitis, and bacterial vaginitis were the
      three most common RTIs among our participants. Television, radio broadcast, and
      public education during screening were the major source of healthcare knowledge
      in rural China. Moreover 99.7% of women expressed great interest in participating
      in a combined screening project. The affordable limit for combined screening
      project was only 50 RMB for more than half of the rural women. CONCLUSION: A
      combined screening program would be more effective and popular than single
      disease screening projects, while appropriate accompanied education and a co-pay
      model for its successful implementation need to be explored, especially in low
      resource settings.

PMID- 22994790
TI  - Experience of Southern Chinese: new challenges in treating young female breast
      cancer patients at child-bearing age--a call for multi-disciplinary
      collaboration.
AB  - Compared with western populations, Southern Chinese, especially those residing in
      Hong Kong, are experiencing increasing breast cancer incidence and also a younger
      onset of breast cancer. Combating this problem and treating young women with
      breast cancer poses specific challenges and complicated considerations. With
      reference to the postponement in the age of marriage and reproduction in modern
      societies, the issue of fertility after breast cancer, especially for high-risk
      young patients, is one significant quality of life concern that cannot be
      underestimated as a secondary medical topic. While the issue has its significance
      and is confronting front-line breast cancer care teams of different disciplines,
      related research is mostly on Caucasians. In cultures where the traditional
      expectation on women for child-bearing is still prominent, young breast cancer
      patients may endure significant distress over fertility options after breast
      cancer. There is a lack of related data on Asian breast cancer survivors at child
      bearing age, which calls for a pressing need to encourage qualitative groundwork,
      case reports, and cohort experiences in hope for providing insight and arouse
      research interest. In order to provide a long-term comprehensive
      multidisciplinary management service with encouragement to encompass prospects
      for a positive future among young breast cancer survivors, relevant disciplines
      need to collaborate and work efficaciously together both on clinical and research
      aspects of cancer-related fertility issues.

PMID- 22994791
TI  - Growth hormone deficiency due to sports-related head trauma is associated with
      impaired cognitive performance in amateur boxers and kickboxers as revealed by
      P300 auditory event-related potentials.
AB  - OBJECTIVES: It has been recently reported that boxing and kickboxing may cause
      pituitary dysfunction, GH deficiency in particular. The strong link between poor
      cognitive performance and GH deficiency due to causes other than head trauma and
      the improvement of cognitive function after GH replacement therapy have been
      previously shown. P300 auditory event-related potential (ERP) measure is widely
      used to evaluate cognitive performance. In this study, we investigated the
      relation between the GH-IGF-I axis and cognitive performance in boxers and
      kickboxers. DESIGN AND PATIENTS: Forty-one actively competing or retired male
      boxers (n: 27) and kickboxers (n: 14) with a mean age of 29.04 +/- 9.30 year and
      14 age- and education-matched healthy male controls were included in the study.
      For neuropsychological tests, the mini-mental state examination (MMSE) and
      Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) questionnaires
      were administered. Moreover, cognitive performance was evaluated according to
      P300 ERPs. RESULTS: Nine of 41 (21.9%) athletes had GH deficiency. P300
      amplitudes were lower at all electrode sites in the GH-deficient group than in
      controls, and the differences were statistically significant at Fz and Oz
      electrode sites (P < 0.05). When GH-deficient athletes were compared with GH
      sufficient athletes, the P300 amplitudes were lower at all electrode sites in the
      GH-deficient group; these differences were statistically significant at Fz, Pz
      and Cz electrode sites (P < 0.05). In all athletes, there were significant
      negative correlations between IGF-I levels vs P300 latencies, and there were
      significant positive correlations between IGF-I levels vs P300 amplitudes (P <
      0.05). CONCLUSION: This study provides the first electrophysiological evidence
      for the close relation between the P300 ERPs and the GH-IGF-I axis in boxers and
      kickboxers.

PMID- 22994792
TI  - Substandard care in delivery-related asphyxia among term infants: prospective
      cohort study.
AB  - OBJECTIVE: To assess substandard care factors in the case of delivery-related
      asphyxia. DESIGN: Prospective cohort study. SETTING: Catchment area of the
      Neonatal Intensive Care Unit (NICU) of the University Medical Center Utrecht; a
      region in the middle of the Netherlands covering 13% of the Dutch population.
      POPULATION: Term infants, without congenital malformations, who died intrapartum
      or were admitted to the Neonatal Intensive Care Unit due to asphyxia. METHODS:
      During a two-year period, cases were prospectively collected and audited by an
      expert panel. MAIN OUTCOME MEASURES: Substandard care factors. RESULTS: 37 735
      term infants without congenital malformations were born. There were 19
      intrapartum deaths, and 89 NICU admissions of which 12 neonates died. In 63 (58%)
      cases a substandard care factor was identified that was possibly (n= 47, 43%) or
      probably (n= 16, 15%) related to perinatal death or NICU admission. In primary
      care, substandard care factors were mainly the low frequency of examination
      during labor and delay in referral to secondary care. In secondary care,
      misinterpretation of cardiotocography and failure to respond adequately to
      clinical signs of fetal distress were the most common substandard care factors.
      CONCLUSIONS: Substandard care is present in a substantial number of cases with
      delivery-related asphyxia resulting in perinatal death or NICU admission.
      Improving the organization of obstetric care in the Netherlands as well as
      training of obstetric caregivers might reduce adverse outcomes.

PMID- 22994793
TI  - Pancreatic insufficiency in patients with HIV infection: role of didanosine
      questioned.
AB  - OBJECTIVES: The aim of the study was to identify possible causes of pancreatic
      insufficiency in patients with HIV infection. METHODS: A retrospective analysis
      of 233 HIV-positive patients for whom faecal elastase measurement was available
      was performed to investigate potential associations with core demographic data,
      HIV infection characteristics, degree of immunosuppresion, exposure to
      antiretroviral therapy (ART), alcohol misuse, diabetes, hepatitis C virus (HCV)
      infection, triglyceride and cholesterol levels and symptomatology. The response
      to pancreatic enzyme replacement for patients with evidence of insufficiency was
      also evaluated. RESULTS: Of 233 patients, 104 (45%) had evidence of pancreatic
      exocrine insufficiency (faecal elastase < 200 mcg/g). A positive association with
      exocrine pancreatic insufficiency was found for HCV infection (P = 0.007),
      previous or current HCV treatment (P = 0.003), alcohol misuse history (P = 0.006)
      and the presence of steatorrhoea (P = 0.03). There was no demonstrated
      association between exocrine pancreatic insufficiency and didanosine (ddI)
      exposure (P = 0.43) or stavudine (d4T) exposure (P = 0.62). Seventy-seven per
      cent of patients who were treated with pancreatic enzymatic supplementation
      reported a subjective improvement in symptoms. CONCLUSIONS: Faecal elastase
      sampling should form part of the routine work-up for HIV-positive patients with
      chronic diarrhoea even in the absence of 'traditional' risk factors such as ddI
      exposure. In particular, if the patient has steatorrhoea, a history of alcohol
      exposure or their HCV serology is positive, they should be considered for
      investigation. Treatment with pancreatic enzyme supplementation appears to be
      effective in the treatment of chronic diarrhoea caused by pancreatic
      insufficiency in the majority of patients.

PMID- 22994794
TI  - Validation of the Parental-Caregiver Perceptions Questionnaire: agreement between
      parental and child reports.
AB  - OBJECTIVES: To test the validity and reliability of Brazilian Portuguese version
      of the Parental-Caregiver Perceptions Questionnaire (P-CPQ) (Aim 1) and to assess
      the agreement between parents and children concerning the child's oral health
      related quality of life (OHRQoL) (Aim 2). METHODS: The P-CPQ and the Brazilian
      Portuguese versions of the Child Perceptions Questionnaires (CPQ8-10 and CPQ11-14
      ) were used. Objective 1 addressed in the study that involved 210 (validity and
      internal reliability) and 20 (test-retest reliability) parents and Objective 2 in
      the study that involved 210 pairs of parents and children. Construct validity was
      calculated using the Spearman's correlation and the Mann-Whitney/Kruskal-Wallis
      tests. Reliability was determined using Cronbach's alpha and intraclass
      correlation coefficient (ICC). Agreement between overall and subscale scores
      derived from the P-CPQ and CPQ was assessed in comparison and correlation
      analyses. RESULTS: The P-CPQ discriminated among the categories of malocclusion
      and dmft. The P-CPQ showed good construct validity, good internal consistency
      reliability, and excellent test-retest reliability. There was systematic under-
      and overreporting in parents' assessments for younger and older children,
      respectively. However, the magnitude of the directional differences was just
      small. At individual level, agreement between parents and children was excellent.
      However, it ranged from excellent to moderate or substantial in subscales for
      CPQ8-10 and CPQ11-14 groups, respectively. CONCLUSIONS: The Portuguese version of
      P-CPQ is valid and reliable. Some parents have limited knowledge about child
      OHRQoL. Given that parental and child reports measure different realities
      concerning the child's OHRQoL, information provided by parents can complement the
      child's evaluation.

PMID- 22994796
TI  - Heparin-induced multiple electrode aggregometry is a promising and useful
      functional tool for heparin-induced thrombocytopenia diagnosis: confirmation in a
      prospective study.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially lethal adverse effect of
      heparin therapy. Accurate and rapid HIT laboratory diagnosis when HIT is
      suspected is crucial. The combination of an immunological assay with a functional
      test improves the accuracy of HIT, but functional assays are currently limited to
      a few laboratories. Multiplate(r) analyzer (Dynabyte, Munich, Germany) is a
      practical, semi-automated and easy-to-perform platelet aggregation assay. The aim
      of this study is to explore whether heparin-induced platelet aggregation in whole
      blood assessed by Multiplate(r) (Heparin-induced multiple electrode aggregometry,
      HIMEA) can replace platelet aggregation test (PAT) in platelet-rich plasma. For
      this purpose, HIMEA performance in HIT diagnosis was prospectively evaluated.
      HIMEA and PAT were compared to serotonin-release assay (SRA) in 200 well
      characterized consecutive patients suspected for HIT. HIMEA was found to be more
      sensitive (81% vs. 76%) and more specific (99% vs. 96%) than PAT compared to SRA.
      Both tests showed a high negative predictive value while HIMEA had a better
      positive predictive value. HIMEA has overall better performance characteristics
      than PAT for the detection of HIT platelet-activating antibodies. The combination
      of an immunological assay with HIMEA could be a feasible option in non
      specialized laboratories for HIT diagnosis optimization. 

PMID- 22994797
TI  - High cell-autonomy of the anterior endomesoderm viewed in blastomere fate shift
      during regulative development in the isolated right halves of four-cell stage
      Xenopus embryos.
AB  - The isolated right half (RH) or left half (LH) of Xenopus embryos can undergo
      regulation so as to form well-proportioned larvae. To assess how the combined
      actions of maternal determinants and cell-cell interactions contribute to form
      the well-proportioned larvae, we quantitatively compared four-cell stage
      blastomere fate between normal larvae and regulated larvae from RH embryos. In
      normal larvae, the clones of the right dorsal blastomere (RD) and right ventral
      blastomere (RV) were located unilaterally. In contrast, in regulated larvae: (i)
      the RD clone exclusively occupied the anterior endomesoderm (AE) derivatives,
      coinciding no RV progeny in those derivatives of normal larvae. The clone
      bilaterally populated tissues along the dorsal midline, which characteristically
      included the medial regions of both somites adjoining the notochord, with higher
      percentages on the right and anterior sides. (ii) The RV clone extensively
      compensated for the missing left side at the expense of its right side
      contribution, and bilaterally occupied the ventroposterior and also dorsal
      regions excluding the AE derivatives. This clone considerably populated, with
      altered orientations, the derivatives of the left half gastrocoel roof plate
      (GRP), the left half GRP being essential for laterality determination. These
      results show that the high cell-autonomy in the AE constitutes a mechanism common
      to both normal and regulative development. In regulated larvae, cell-cell
      interactions shifted the midlines on the dorsal side slightly and the ventral
      side to a greater extent. The cell lineage difference in the left half GRP could
      result in a different utilization of maternal determinants in that area.

PMID- 22994795
TI  - Sildenafil after cardiac arrest and infarction; an experimental rat model.
AB  - OBJECTIVES: Resuscitation after cardiac arrest may lead to ischemia-reperfusion
      injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5
      inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac
      transplantation model. DESIGN: Sixty-one Fischer344 rats underwent syngeneic
      heterotopic cardiac transplantation after ischemia and ligation of the left
      anterior coronary artery of the heart to yield myocardial infarction (IRI + MI).
      Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI
      +MI + S). Twenty-three additional grafted animals with transplantation only
      served as controls with ischemia reperfusion injury (IRI). After 2 days,
      immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed
      after graft harvesting and histology. RESULTS: Two days after transplantation,
      remote intramyocardial arteries were more preserved in IRI + MI + S as compared
      with IRI +MI and IRI (0.74 +/- 0.14, 0.56 +/- 0.23 and 0.55 +/- 0.22, PSU, p <
      0.05, respectively). Decreased eNOS staining confirmed the presence of developing
      infarction in IRI + MI and IRI + MI + S. The expression of iNOS was significantly
      lower during IRI + MI +S as compared with IRI + MI (0.02 +/- 0.01 and 1.02 +/-
      0.02, FC, p < 0.05). CONCLUSIONS: Administered at the onset of reperfusion and
      developing infarction, sildenafil has an impact on myocardial recovery after
      cardiac arrest and ischemia.

PMID- 22994798
TI  - Intracoronary hemodynamic effects of pressure-controlled intermittent coronary
      sinus occlusion (PICSO): results from the First-In-Man Prepare PICSO Study.
AB  - BACKGROUND:  Myocardial reperfusion is frequently suboptimal after ST-segment
      elevation myocardial infarction (STEMI) treated by primary percutaneous coronary
      intervention (PCI). Using a balloon-tipped catheter positioned in the coronary
      sinus (CS), pressure-controlled intermittent coronary sinus occlusion (PICSO)
      results in an intermittent obstruction of coronary venous outflow of the left
      anterior descending artery (LAD), and may improve myocardial perfusion by
      augmenting redistribution of blood to the border zone of ischemic myocardium. We
      sought to document the intracoronary hemodynamic effects of PICSO during PCI.
      METHODS:  We included 15 patients with stable angina scheduled for PCI of the
      LAD. Balloon occlusion of the LAD was performed twice, once with and once without
      PICSO and lasting maximally 3 minutes each, to document the effect of PICSO on CS
      pressure and LAD wedge pressure. RESULTS:  Catheter delivery was successful in
      all patients. The study protocol could not be conducted in 5 patients due to
      initial calibration difficulties (n = 3), a pressure wire problem (n = 1), and a
      vagal response at the start of the procedure (n = 1). In the remaining 10
      patients, CS occlusion caused a marked increase in mean CS pressure (4.1 +/- 7.3
      mmHg vs. 22.0 +/- 12.6 mmHg; P < 0.001) and CS pulse pressure (4.3 +/- 0.8 mmHg
      vs. 36.1 +/- 6.3 mmHg; P < 0.001). Concomitantly, mean distal LAD wedge pressure
      and wedge pulse pressure increased (32.4 +/- 12.2 mmHg vs. 35.5 +/- 12.6 mmHg; P
      < 0.001 and 39.1 +/- 27.2 mmHg vs. 45.9 +/- 26.0 mmHg; P < 0.001, respectively).
      At 30 day follow-up, no device-related events occurred. CONCLUSIONS:  PICSO
      safely augments CS pressure, thereby increasing LAD coronary wedge pressure.
      These findings support further evaluation of PICSO in the setting of STEMI.

PMID- 22994799
TI  - Age-related changes in rat genioglossus, geniohyoid and masseter muscles.
AB  - OBJECTIVES: The aim of this study was to elucidate age-related changes from adult
      to middle age in the contractile properties of the masseter, genioglossus and
      geniohyoid muscles of the rat. MATERIALS AND METHODS: We analysed the expressions
      of myosin heavy chain (MyHC) mRNAs and proteins as indicators of the contractile
      properties in these muscles obtained from rats at 6, 12, 18 and 24 months of age
      using real-time PCR and SDS-PAGE. RESULTS: We found no marked age-related changes
      in the expressions of MyHC mRNAs and proteins in rat masseter and geniohyoid
      muscles, suggesting that the biological ageing process does not affect
      contractile properties in these muscles. However, we found a decrease in the
      expression of MyHC IIb mRNA with ageing in the rat genioglossus muscle,
      suggesting that biological ageing process induces at least some fast-to-slow
      myofibre phenotype transition. CONCLUSION: The biological ageing process from
      adult to middle age appears to differentially affect different types of
      craniofacial muscles.

PMID- 22994801
TI  - Synthesis and paroxonase activities of novel bromophenols.
AB  - Three novel bromophenols 10-12 were synthesized. Acylation of veratrole (4) with
      2,3-dimethoxy benzoic acid (5) gave a kown diarylmethanone 6. Bromination of 6
      with different equivalents of molecular bromine afforded new di and tribrominated
      compounds 7-9 which were converted to their corresponding bromophenols 10-12 via
      O-demethylation with BBr3. Paraoxonase-1 (PON1) was purified from human serum
      with approximately 42% and 3584 U * mg(-1) specific activity. The synthesized
      compounds 6-12 showed inhibitory effects on paraoxonase-1 (PON1) which is an
      organophosphate (OP) hydrolyser and an antioxidant bioscavenger enzyme. IC50
      values were determined in the range of 0.123-1.212 mM.

PMID- 22994802
TI  - Altered balance between effector T cells and FOXP3+ HELIOS+ regulatory T cells
      after thymoglobulin induction in kidney transplant recipients.
AB  - This study examined the effect of thymoglobulin induction therapy on leukocyte
      population dynamics in kidney transplant patients. Patients receiving standard
      immunosuppression were compared with those who received additional thymoglobulin
      at the time of kidney transplantation. Thymoglobulin induction led to an
      immediate and significant decrease of all T cells and NK cells, but not B cells
      or monocytes. CD8(+)  T cells recovered to near pretransplant level by 4 weeks
      post-transplant. CD4(+)  T cells remained at less than 30% of pretransplant level
      for the entire study period of 78 weeks. Both CD4(+)  and CD8(+)  T cells showed
      reduced cytokine production after recovery. Deletion of CD4(+) FOXP3(+) HELIOS(+)
      regulatory T cells (Tregs) was less profound than that of CD4(+) FOXP3(-) 
      cells, thus the relative percentage of Tregs elevated significantly when compared
      with pretransplant levels in thymoglobulin-treated patients. In contrast, the
      percentages of Tregs and their expression of FOXP3 in the standard
      immunosuppression group decreased steadily and by 12 weeks after transplant the
      average percentage of Tregs was 56% of the pretransplant level. Thus,
      thymoglobulin-induced deletion of T cells led to significant and long-lasting
      alterations of the T-cell compartment characterized by a preservation of Tregs
      and long-lasting reduction in CD4(+) , and potentially pathogenic, T cells.

PMID- 22994803
TI  - Bleeding disorders, menorrhagia and iron deficiency: impacts on health-related
      quality of life.
AB  - von Willebrand disease (VWD) is a bleeding disorder that occurs in up to 1% of
      the general population. The great majority of females with VWD experience
      menorrhagia. The morbidity burden in females with VWD may relate to iron
      deficiency resulting from menorrhagia. To explore relationships between bleeding
      disorders, menorrhagia, iron deficiency and the outcomes of health-related
      quality of life (HRQL) and educational attainment. All subjects with VWD, and
      females with other bleeding disorders, in the Canadian national registry who were
      more than 12 years of age were eligible for survey. Survey measures included the
      HEALTH UTILITIES INDEX((r)); abridged Clinical History Assessment Tool; socio
      demographic questions and serum ferritin. Statistical analyses included testing
      differences among groups of means using analysis of variance and of proportions
      using chi-squared test. Significant size differences in mean HRQL scores were
      detected between VWD females and both females with other bleeding disorders [diff
      = (-0.08); P = 0.017] and VWD males [diff = (-0.07); P = 0.039]. Mean HRQL scores
      differed between females with and without menorrhagia (P < 0.001). Mean HRQL
      scores were not significantly different between females with and without iron
      deficiency. Educational attainment was not associated with disease group,
      menorrhagia status or iron status. Females with VWD have a greater morbidity
      burden than females in the general population, females with other bleeding
      disorders and males with VWD. Menorrhagia is associated with low HRQL scores in
      females with bleeding disorders, including VWD. Further investigation should
      assess how menorrhagia impacts HRQL in females with bleeding disorders.

PMID- 22994805
TI  - Rapid evolution of sex frequency and dormancy as hydroperiod adaptations.
AB  - Dormancy can serve as an adaptation to persist in variable habitats and often is
      coupled with sex. In cyclically parthenogenetic rotifers, an asexual phase
      enables rapid population growth, whereas sex results in diapausing embryos
      capable of tolerating desiccation. Few studies have experimentally tested whether
      sex-dormancy associations in temporary waters reflect evolution in response to
      the short hydroperiod selecting for diapause ability. Here, we demonstrate
      evolution of higher propensity for sex and dormancy in ephemeral rotifer cultures
      mimicking temporary ponds, and lower propensity in permanent cultures. Results
      are consistent with rapid evolution, with evolutionary changes occurring in a
      short timeframe (385 days, <= 84 generations). We also provide insight into
      mechanisms for rapid evolution in basal metazoans, discussing potential roles of
      new mutations, recombination and clonal selection.

PMID- 22994804
TI  - Differing effects of rapamycin or calcineurin inhibitor on T-regulatory cells in
      pediatric liver and kidney transplant recipients.
AB  - In a cross-sectional study, we assessed effects of calcineurin inhibitor (CNI) or
      rapamycin on T-regulatory (Treg) cells from children with stable liver (n = 53)
      or kidney (n = 9) allografts several years posttransplant. We analyzed Treg
      number, phenotype, suppressive function, and methylation at the Treg-specific
      demethylation region (TSDR) using Tregs and peripheral blood mononuclear cells.
      Forty-eight patients received CNI (39 as monotherapy) and 12 patients received
      rapamycin (9 as monotherapy). Treg numbers diminished over time on either
      regimen, but reached significance only with CNI (r =-0.424, p = 0.017). CNI
      levels inversely correlated with Treg number (r =-0.371, p = 0.026), and
      positively correlated with CD127+ expression by Tregs (r = 0.437, p = 0.023).
      Patients with CNI levels >3.6 ng/mL had weaker Treg function than those with
      levels <3.6 ng/mL, whereas rapamycin therapy positively correlated with Treg
      numbers (r = 0.628, p = 0.029) and their expression of CTLA4 (r = 0.726, p =
      0.041). Overall, CTLA4 expression, TSDR demethylation and an absence of CD127
      were important for Treg suppressive function. We conclude that rapamycin has
      beneficial effects on Treg biology, whereas long-term and high dose CNI use may
      impair Treg number, function and phenotype, potentially acting as a barrier to
      attaining host hyporesponsiveness to an allograft.

PMID- 22994807
TI  - Layers of complexity.

PMID- 22994806
TI  - A MultiSite GatewayTM vector set for the functional analysis of genes in the
      model Saccharomyces cerevisiae.
AB  - BACKGROUND: Recombinatorial cloning using the GatewayTM technology has been the
      method of choice for high-throughput omics projects, resulting in the
      availability of entire ORFeomes in GatewayTM compatible vectors. The MultiSite
      GatewayTM system allows combining multiple genetic fragments such as promoter,
      ORF and epitope tag in one single reaction. To date, this technology has not been
      accessible in the yeast Saccharomyces cerevisiae, one of the most widely used
      experimental systems in molecular biology, due to the lack of appropriate
      destination vectors. RESULTS: Here, we present a set of three-fragment MultiSite
      GatewayTM destination vectors that have been developed for gene expression in S.
      cerevisiae and that allow the assembly of any promoter, open reading frame,
      epitope tag arrangement in combination with any of four auxotrophic markers and
      three distinct replication mechanisms. As an example of its applicability, we
      used yeast three-hybrid to provide evidence for the assembly of a ternary complex
      of plant proteins involved in jasmonate signalling and consisting of the JAZ,
      NINJA and TOPLESS proteins. CONCLUSION: Our vectors make MultiSite GatewayTM
      cloning accessible in S. cerevisiae and implement a fast and versatile cloning
      method for the high-throughput functional analysis of (heterologous) proteins in
      one of the most widely used model organisms for molecular biology research.

PMID- 22994808
TI  - The need and direction for drug law reform in Australia.

PMID- 22994809
TI  - A life-cycle approach to monitoring benefits and harms of medicines.

PMID- 22994812
TI  - e-Health records: beware of assumed benefit.

PMID- 22994813
TI  - Highly sensitive troponin assays--a two-edged sword?

PMID- 22994814
TI  - What the public learns about screening and diagnostic tests through the media.

PMID- 22994815
TI  - A journalist's view of reporting medical tests.

PMID- 22994816
TI  - Designing incentives for good-quality hospital care.

PMID- 22994817
TI  - Not window dressing, but key to making medical research matter.

PMID- 22994818
TI  - Training doctors--too long in the cellar?

PMID- 22994819
TI  - Training doctors--too long in the cellar? Comment.

PMID- 22994820
TI  - The need for data beyond primary diagnosis.

PMID- 22994821
TI  - Pharmacoepidemiology of testosterone prescribing in Australia, 1992-2010.

PMID- 22994822
TI  - Pharmacoepidemiology of testosterone prescribing in Australia, 1992-2010.

PMID- 22994823
TI  - The use of key performance indicators to benchmark individual clinic performance
      in managing a complex chronic infectious disease.

PMID- 22994824
TI  - A battlefield occupational risk not to be ignored.

PMID- 22994825
TI  - Simulation in clinical teaching and learning.

PMID- 22994826
TI  - Screening with nucleic acid amplification tests for gonorrhoea in men who have
      sex with men.

PMID- 22994827
TI  - Myopathy and possible intestinal dysfunction in a patient treated with colchicine
      and simvastatin.

PMID- 22994828
TI  - Medical schools as agents of change: socially accountable medical education.

PMID- 22994829
TI  - Shared care for chronic eye diseases: perspectives of ophthalmologists,
      optometrists and patients.

PMID- 22994830
TI  - Use of adrenaline in digital nerve blocks.

PMID- 22994831
TI  - A national study of workplace aggression in Australian clinical medical practice.
AB  - OBJECTIVE: To describe the 12-month prevalence of verbal or written and physical
      aggression from patients, patients' relatives or carers, coworkers and others in
      Australian clinical medical practice. DESIGN, SETTING AND PARTICIPANTS: An
      exploratory, descriptive study of cross-sectional survey design in the third wave
      (March 2010 to June 2011) of the Medicine in Australia: Balancing Employment and
      Life longitudinal survey. MAIN OUTCOME MEASURES: Proportions of clinicians
      reporting verbal or written and physical aggression from each aggression source
      and the significance of differences reported by doctor type, sex, international
      medical graduate status, age and postgraduate experience. RESULTS: Of 16,327
      medical practitioners sampled, a response rate of 60.9% (9951) was achieved and
      9449 (57.9%) were in Australian clinical practice. Participants comprised 3515
      general practitioners and GP registrars, 3875 specialists, 1171 hospital non
      specialists and 888 specialists in training. Overall, 70.6% of medical
      practitioners experienced verbal or written aggression and 32.3% experienced
      physical aggression from one or more sources in the previous 12 months. While
      patterns of exposure were complex, more female clinicians, international medical
      graduates (IMGs) and hospital-based clinicians experienced workplace aggression.
      Age and postgraduate experience were significantly negatively associated with
      aggression exposure. CONCLUSIONS: This is the first nationwide study of workplace
      aggression from all sources experienced by all subpopulations of Australian
      medical clinicians. The findings suggest particular risks for younger and more
      junior hospital-based clinicians, and for IMGs in general practice. A failure to
      address this important professional and public health concern may contribute to
      ongoing challenges in the recruitment and retention of medical practitioners in
      an era of increasing shortages internationally.

PMID- 22994832
TI  - Trends in alcohol-attributable hospitalisation in the Northern Territory, 1998-99
      to 2008-09.
AB  - OBJECTIVE: To examine trends in hospitalisation for alcohol-attributable
      conditions in the Northern Territory Aboriginal and non-Aboriginal populations
      between the financial years 1998-99 and 2008-09. DESIGN AND SETTING:
      Retrospective descriptive analysis of inpatient discharge data from NT public
      hospitals. MAIN OUTCOME MEASURES: Alcohol-attributable hospitalisation by age,
      sex, Aboriginality, region of residence and medical conditions, with annual time
      trends. RESULTS: Annual rates of hospitalisation for alcohol-attributable
      conditions across the NT increased from 291.3 per 10,000 population to 460.0 per
      10,000 (57.9%) among Aboriginal males and from 181.8 per 10,000 to 387.4 per
      10,000 (113.1%) among Aboriginal females over the study period. The alcohol
      attributable hospitalisation rate also increased from 58.8 per 10,000 population
      to 87.4 per 10,000 (48.6%) among non-Aboriginal males and from 16.8 per 10,000 to
      37.2 per 10,000 (121.4%) among non-Aboriginal females. Alcohol-attributable
      hospitalisation rates among Aboriginal people living in Central Australia were
      much higher than in the Top End. In Central Australia, the rates for Aboriginal
      females increased throughout the study period, but for Aboriginal males declined
      from 2004-05 onwards. CONCLUSION: Rates of hospitalisation for alcohol
      attributable conditions were high among NT Aboriginal people and increased during
      the study period. Although not statistically significant, the moderation in rates
      among Central Australian Aboriginal males after 2004-05 is encouraging. This
      apparent improvement is consistent with another recent study and provides
      tentative support that recent policy changes and interventions may be having an
      impact. The results of this study highlight the burden of alcohol use in the NT
      and emphasise the need for ongoing investment in comprehensive alcohol-management
      programs.

PMID- 22994833
TI  - The comparability of emergency department waiting time performance data.
AB  - OBJECTIVE: To examine whether the reported urgency mix of an emergency
      department's (ED's) patients is associated with its waiting time performance.
      DESIGN AND SETTING: Cross-sectional analysis of data on patient urgency mix and
      hospital ED performance reported on the MyHospitals website for July 2009 - June
      2010. MAIN OUTCOME MEASURES: ED performance assessed as the proportion of
      patients whose care was initiated within the recommended time frame for each of
      four triage categories. RESULTS: Data for 158 hospitals showed that EDs with a
      higher proportion of patients assigned to the emergency category have poorer
      waiting time performance, after adjusting for hospital characteristics.
      Conversely, EDs with a higher proportion of patients assigned to the non-urgent
      category perform better. If performance scores were adjusted for reported patient
      urgency mix and hospital peer group, mean adjustments would be modest in size
      (3.7-7.1 percentage points, depending on the category), but for individual EDs
      the differences could be large (as large as 31 percentage points) and hospital
      waiting time performance rankings would be substantively impacted. CONCLUSION:
      Since ED performance is related to reported patient urgency mix, adjusting for
      casemix in the ED may be warranted to ensure valid comparisons between hospitals.
      Further investigation of the validity of performance measures and appropriate
      adjustment for differences in hospital and patient characteristics is required if
      public reporting is to meet its goals.

PMID- 22994834
TI  - Carbon monoxide-induced death and toxicity from charcoal briquettes.

PMID- 22994835
TI  - Chromoblastomycosis in a Solomon Islander.

PMID- 22994836
TI  - The MJA, MDA National, Nossal Global Health Prize: broadening our horizons.

PMID- 22994837
TI  - The sound of silence: global health challenges from the front.

PMID- 22994839
TI  - Cryptography in modern-day medical science.

PMID- 22994840
TI  - Intratesticular lidocaine reduces the response to surgical castration in dogs.
AB  - OBJECTIVE: To investigate whether intratesticular injection of lidocaine pre
      surgery would reduce the intraoperative responses to elective castration in dogs.
      STUDY DESIGN: Double-blinded, randomized, controlled, prospective clinical study.
      ANIMALS: Forty-two client-owned dogs weighing 2.2-38.4 kg and aged between 4.5
      and 56 months. METHODS: Group L dogs received an intratesticular injection of 2%
      lidocaine (2 mg kg(-1)) and Group S an identical volume of saline prior to
      surgery. Premedication was with acepromazine and morphine intramuscularly.
      Anaesthesia was induced with propofol intravenously and maintained with
      isoflurane vaporized in oxygen. Heart rate (HR), mean arterial pressure (MAP),
      respiratory rate (f(R)), end-tidal isoflurane (Fe'ISO) and carbon dioxide
      concentrations, oxygen saturation and ECG were monitored during surgery. Fe'ISO
      was maintained at 1.0+/-0.1%. Supplemental propofol was given in response to
      gross movement. RESULTS: Group L had significantly lower maximum values for both
      HR and MAP. Group L displayed significantly smaller increases in HR during
      exteriorization of the first testis than Group S. There was an overall
      significant difference in MAP between groups during all surgical events (p=0.041)
      and time points (p=0.002). In univariate analysis, Group L showed significantly
      less changes in MAP during skin incision, exteriorization of the first testis and
      clamping of both spermatic cords. Group S reached its highest f(R) significantly
      earlier. Group L (eight dogs) required additional propofol 33+/-18 minutes after
      the start of surgery and Group S (seven dogs) at 19+/-17 minutes; this difference
      was not statistically significant. Seven dogs in Group L and 12 dogs in Group S
      required rescue analgesia with morphine (GCMPS-SF score >=6); this difference was
      not statistically significant. No adverse effects were reported postoperatively.
      CONCLUSIONS AND CLINICAL RELEVANCE: Based on this study, the authors recommend
      the use of intratesticular lidocaine for surgical castration in dogs.

PMID- 22994841
TI  - Brief heat treatment causes a structural change and enhances cytotoxicity of the
      Escherichia coli alpha-hemolysin.
AB  - alpha-Hemolysin (HLY) is an important virulence factor for uropathogenic
      Escherichia coli. HLY is a member of the RTX family of exotoxins secreted by a
      number of Gram-negative bacteria. Recently, it was reported that a related RTX
      toxin, the Mannheimia haemolytica leukotoxin, exhibits increased cytotoxicity
      following brief heat treatment. In this article, we show that brief heat
      treatment (1 min at 100 degrees C) increases cytotoxicity of HLY for human
      bladder cells, kidney epithelial cells (A498) and neutrophils. Heat treatment
      also increased hemolysis of human red blood cells (RBCs). Furthermore, heat
      treatment of previously inactived HLY restored its cytotoxicity. Heat-activated
      and native HLY both required glycophorin A to lyse RBCs. Native and heat
      activated HLY appeared to bind equally well to the surface of A498 cells;
      although, Western blot analyses demonstrated binding to different proteins on the
      surface. Confocal microscopy revealed that heat-activated HLY bound more
      extensively to internal structures of permeabilized A498 cells than did native
      HLY. Several lines of spectroscopic evidence demonstrate irreversible changes in
      the structure of heat activated compared to native HLY. We show changes in
      secondary structure, increased exposure of tryptophan residues to the aqueous
      environment, an increase in molecular dimension and an increase in hydrophobic
      surface area. These properties are among the most common characteristics
      described for the molten globule state, first identified as an intermediate in
      protein folding. We hypothesize that brief heat treatment of HLY causes a
      conformational change leading to significant differences in protein-protein
      interactions that result in increased cytotoxicity for target cells.

PMID- 22994842
TI  - Computed tomography findings of aspiration pneumonia in 53 patients.
AB  - AIM: No large case series has so far shown the chest computed tomography (CT)
      features in patients with aspiration pneumonia, despite the fact that aspiration
      pneumonia is the most common pulmonary disease in the elderly and is regarded as
      gravity-dependent pneumonia. The aim of the present study was to elucidate the CT
      features based on the patients' status in patients with dysphagia-associated
      aspiration pneumonia. METHODS: A total of 53 patients, who were hospitalized
      because of pneumonia and subsequently confirmed to have dysphagia by
      videofluorography, were entered into this study. The CT findings were
      independently evaluated by two radiologists who were unaware of the patients'
      clinical information. The relationships between the patients' status and the CT
      patterns of pneumonia or their distributions were analyzed. RESULTS: There were
      eight patients (15%) with lobar pneumonia, 36 patients (68%) with
      bronchopneumonia and nine patients (17%) with bronchiolitis. Posterior lung
      predominance was seen in 49 patients (92%). In the craniocaudal observation,
      lower lung predominance was found in 25 patients (47%) and diffuse distribution
      was seen in 28 patients (53%). A decreased performance status was significantly
      associated with a diffuse distribution (P=0.039). CONCLUSIONS: Aspiration
      pneumonia more frequently presented as a bronchopneumonia pattern followed by a
      bronchiolitis pattern on CT. Their distributions were characterized by gravity
      dependence, and anterior- or upper lung-limited pneumonia might not be due to
      dysphagia-associated pneumonia.

PMID- 22994843
TI  - Reducing stress and supporting positive relations in families of young children
      with type 1 diabetes: a randomized controlled study for evaluating the effects of
      the DELFIN parenting program.
AB  - BACKGROUND: To assess initial efficacy and feasibility of a structured
      behavioural group training (DELFIN) for parents of children with diabetes type 1,
      in order to reduce parenting stress and to improve parenting skills. METHODS: A
      randomized controlled study was conducted between July 2008 and September 2010,
      at a children's hospital in Hannover with parents of children with type 1
      diabetes (2-10 yrs) (intervention group n = 37; control group n = 28). Parenting
      skills, parents' psychological burden, children's behavioural difficulties and
      quality of metabolic control were assessed before, 3 months after and 12 months
      after participating in the training program. RESULTS: In the intervention group
      parenting behaviour in conflict situations improved significantly after 3 months
      (Z = -3.28; p <= 0.001). It remained stable over 12 months (Z = -2.94; p <=
      0.01). Depression and anxiety scores of parents decreased (Z = -1.93; p <= .05; Z
      = -2.02; p <= .05). Even though the outcome in the intervention group was more
      positive, the differences between both study arms failed to reach statistical
      significance. Unexpectedly parenting behaviour in the control group improved also
      (Z = -2.45; p <= .05). Anxiety as well as stress scores decreased in this group
      (Z = -2.02; p <= .05 and Z = -2.11; p <= .05). In both groups the initial
      metabolic control was good and without significant differences (A1c 7.2 +/- 0.8%
      vs. 7.1 +/- 0.4%; p > 0.5). It remained stable in the DELFIN group (A1c 7.1 +/-
      0.8%; p > 0.5), but it increased slightly in controls (A1c 7.3 +/- 0.5%; Z = 
      2.79; p = .005). CONCLUSIONS: This study has brought first evidence for the
      efficacy and feasibility of the program. A multicentre study with a larger sample
      is necessary to confirm these first results.

PMID- 22994845
TI  - Atrial fibrillation is associated with increased mean platelet volume in patients
      with type 2 diabetes mellitus.
AB  - Platelet abnormalities in diabetes mellitus (DM) and atrial fibrillation (AF) may
      underline the etiology of a prothrombotic state in these conditions. Increased
      mean platelet volume (MPV) is a marker of abnormal platelet function and
      activation. We aimed to investigate the possible association of chronic AF with
      MPV in patients who have type 2 DM. Patients who had type 2 DM with either
      chronic (>=6 months) AF or normal sinus rhythm (NSR) were included in the study.
      A total of 162 patients (aged 38-89 years) were divided into 2 groups according
      to the presence of either AF or NSR. Group 1 consisted of 81 diabetic patients
      with AF, and group 2 consisted of 81 diabetic patients with NSR. The two groups
      were not significantly different in terms of age, and gender, as well as in
      hypertension, smoking, history of coronary artery disease, previous
      cerebrovascular accidents, microalbuminuria, retinopathy, duration of DM, body
      mass index, hemoglobin A1c, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and triglyceride (p > 0.05 for
      all variables). Although no significant difference was present between groups
      concerning platelet count; for patients with AF, MPV was higher compared with
      patients with NSR (9.0 +/- 0.2 fl vs. 8.4 +/- 0.2 fl; p = 0.001). Furthermore, no
      significant difference was noted between groups regarding routine medications
      received by patients. In multivariate logistic regression analysis, MPV was the
      only variable independently related to AF (OR = 2.659; 95% CI, 1.286-5.498; p =
      0.008). Consequently, it is concluded that AF is associated with increased MPV in
      patients with type 2 DM, suggesting the presence of tentatively related processes
      leading to reciprocal interaction. 

PMID- 22994846
TI  - The psychosocial impact of facial palsy: our experience in one hundred and twenty
      six patients.

PMID- 22994844
TI  - Patient-centered care for older adults with multiple chronic conditions: a
      stepwise approach from the American Geriatrics Society: American Geriatrics
      Society Expert Panel on the Care of Older Adults with Multimorbidity.

PMID- 22994847
TI  - Assam Bora rice starch based biocompatible mucoadhesive microsphere for targeted
      delivery of 5-fluorouracil in colorectal cancer.
AB  - The aim of this study was to develop novel colon targeted mucoadhesive
      microspheres (MAMs) for site specific delivery of 5-fluorouracil (5-FU) to colon
      without the drug being released in the stomach or small intestine. MAMs were
      prepared using Assam Bora rice starch, a natural mucoadhesive polymer, by a
      double emulsion solvent evaporation method. The microspheres were characterized
      for their shape, size, surface morphology, size distribution, incorporation
      efficiency, and in vitro and in vivo drug release studies. The release study
      confirmed the insignificant release of 5-FU in physiological condition of stomach
      and small intestine and major drug release in the cecal content. In vivo release
      study of the optimized MAMs was compared with immediate release (IR) 5-FU. 5-FU
      was distributed predominantly in the upper GI tract from the IR, whereas 5-FU was
      distributed primarily to the lower part of the GI tract from the MAM formulation.
      Enhanced levels of liver enzymes were found in animals given IR 5-FU as well as
      augmented levels of serum albumin, creatinine, leucocytopenia and
      thrombocytopenia was also observed. Thus to sum up, it can be appropriately
      established that the 5-FU release pattern from MAMs exhibits slow and extended
      release over longer periods of time with reduced systemic side effects.

PMID- 22994848
TI  - Use of online sources of information by dental practitioners: findings from The
      Dental Practice-Based Research Network.
AB  - OBJECTIVE: Estimate the proportion of dental practitioners who use online sources
      of information for practice guidance. METHODS: From a survey of 657 dental
      practitioners in The Dental Practice-Based Research Network, four indicators of
      online use for practice guidance were calculated: read journals online, obtained
      continuing education (CDE) through online sources, rated an online source as most
      influential, and reported frequently using an online source for guidance.
      Demographics, journals read, and use of various sources of information for
      practice guidance in terms of frequency and influence were ascertained for each.
      RESULTS: Overall, 21 percent (n = 138) were classified into one of the four
      indicators of online use: 14 percent (n = 89) rated an online source as most
      influential and 13 percent (n = 87) reported frequently using an online source
      for guidance; few practitioners (5 percent, n = 34) read journals online, fewer
      (3 percent, n = 17) obtained CDE through online sources. Use of online
      information sources varied considerably by region and practice characteristics.
      In general, the four indicators represented practitioners with as many
      differences as similarities to each other and to offline users. CONCLUSION: A
      relatively small proportion of dental practitioners use information from online
      sources for practice guidance. Variation exists regarding practitioners' use of
      online source resources and how they rate the value of offline information
      sources for practice guidance.

PMID- 22994849
TI  - Method-specific serum cortisol responses to the adrenocorticotrophin test:
      comparison of gas chromatography-mass spectrometry and five automated
      immunoassays.
AB  - OBJECTIVE: The serum cortisol response to the adrenocorticotrophin (ACTH) test is
      known to vary significantly by assay, but lower reference limits (LRL) for this
      response have not been established by the reference gas chromatography-mass
      spectrometry (GC-MS) method or modern immunoassays. We aimed to compare the
      normal cortisol response to ACTH stimulation using GC-MS with five widely used
      immunoassays. DESIGN, PATIENTS AND MEASUREMENTS: An ACTH test (250 MUg iv ACTH1
      24 ) was undertaken in 165 healthy volunteers (age, 20-66 years; 105 women, 24 of
      whom were taking an oestrogen-containing oral contraceptive pill [OCP]). Serum
      cortisol was measured using GC-MS, Advia Centaur (Siemens), Architect (Abbott),
      Modular Analytics E170 (Roche), Immulite 2000 (Siemens) and Access (Beckman)
      automated immunoassays. The estimated LRL for the 30 min cortisol response to
      ACTH was derived from the 2.5th percentile of log-transformed concentrations.
      RESULTS: The GC-MS-measured cortisol response was normally distributed in males
      but not females, with no significant gender difference in baseline or post-ACTH
      cortisol concentration. Immunoassays were positively biased relative to GC-MS,
      except in samples from women on the OCP, who showed a consistent negative bias.
      The LRL for cortisol was method-specific [GC-MS: 420 nm; Architect: 430 nm;
      Centaur: 446 nm; Access 459 nm; Immulite (2000) 474 nm] and, for the E170, also
      gender-specific (female: 524 nm; male 574 nm). A separate LRL is necessary for
      women on the OCP. CONCLUSIONS: Normal cortisol responses to the ACTH test are
      influenced significantly by assay and oestrogen treatment. We recommend the use
      of separate reference limits in premenopausal women on the OCP and warn users
      that cortisol measurements in this subgroup are subject to assay interference.

PMID- 22994850
TI  - Carvacrol together with TRPC1 elimination improve functional recovery after
      traumatic brain injury in mice.
AB  - Death of Central Nervous System (CNS) neurons following traumatic brain injury
      (TBI) is a complex process arising from a combination of factors, many of which
      are still unknown. It has been found that inhibition of transient receptor
      potential (TRP) channels constitutes an effective strategy for preventing death
      of CNS neurons following TBI. TRP channels are classified into seven related
      subfamilies, most of which are Ca(2+) permeable and involved in many cellular
      functions, including neuronal cell death. We hypothesized that TRP channels of
      the TRPC subfamily may be involved in post-TBI pathophysiology and that the
      compound 5-isopropyl-2-methylphenol (carvacrol), by inhibition of TRP channels,
      may exert neuroprotective effect after TBI. To test these suppositions, carvacrol
      was given to mice after TBI and its effect on their functional recovery was
      followed for several weeks. Our results show that neurological recovery after TBI
      was significantly enhanced by application of carvacrol. To better define the type
      of the specific channel involved, the effect of carvacrol on the extent and speed
      of recovery after TBI was compared among mice lacking TRPC1, TRPC3, or TRPC5,
      relative to wild type controls. We found that neurological recovery after TBI was
      significantly enhanced by combining carvacrol with TRPC1 elimination, but not by
      the absence of TRPC3 or TRPC5, showing a synergistic effect between carvacrol
      application and TRPC1 elimination. We conclude that TRPC1-sensitive mechanisms
      are involved in TBI pathology, and that inhibition of this channel by carvacrol
      enhances recovery and should be considered for further studies in animal models
      and humans.

PMID- 22994851
TI  - Milrinone and levosimendan administered after reperfusion improve myocardial
      stunning in swine.
AB  - OBJECTIVES: We assessed the effect of milrinone application timing after
      reperfusion against myocardial stunning as compared with levosimendan in swine.
      Furthermore, we examined the role of p38 mitogen-activated protein kinase (p38
      MAPK) in the milrinone-induced cardioprotection. DESIGN: All swine were subjected
      to 12-minutes ischemia followed by 90-minutes reperfusion to generate stunned
      myocardium. Milrinone or levosimendan was administered intravenously either for
      20 minutes starting just after reperfusion or for 70 minutes starting 20 minutes
      after reperfusion. In another group, SB203580, a selective p38 MAPK inhibitor,
      was administered with and without milrinone. Regional myocardial contractility
      was assessed by percent segment shortening (%SS). RESULTS: Milrinone starting
      just after reperfusion, but not starting 20 minutes after reperfusion, improved
      %SS at 30, 60, and 90 minutes after reperfusion compared with that in the control
      group. SB203580 abolished the beneficial effect of milrinone. On the other hand,
      levosimendan starting 20 minutes after reperfusion, but not for 20 minutes
      starting just after reperfusion, improved %SS at 60 and 90 minutes after
      reperfusion. CONCLUSIONS: Milrinone should be administered just after reperfusion
      to protect myocardial stunning through p38 MAPK, whereas levosimendan improvement
      of contractile function could be mainly dependent on its positive inotropic
      effect.

PMID- 22994852
TI  - Identification and characterization of small molecule inhibitors of a plant
      homeodomain finger.
AB  - A number of histone-binding domains are implicated in cancer through improper
      binding of chromatin. In a clinically reported case of acute myeloid leukemia
      (AML), a genetic fusion protein between nucleoporin 98 and the third plant
      homeodomain (PHD) finger of JARID1A drives an oncogenic transcriptional program
      that is dependent on histone binding by the PHD finger. By exploiting the
      requirement for chromatin binding in oncogenesis, therapeutics targeting histone
      readers may represent a new paradigm in drug development. In this study, we
      developed a novel small molecule screening strategy that utilizes HaloTag
      technology to identify several small molecules that disrupt binding of the
      JARID1A PHD finger to histone peptides. Small molecule inhibitors were validated
      biochemically through affinity pull downs, fluorescence polarization, and histone
      reader specificity studies. One compound was modified through medicinal chemistry
      to improve its potency while retaining histone reader selectivity. Molecular
      modeling and site-directed mutagenesis of JARID1A PHD3 provided insights into the
      biochemical basis of competitive inhibition.

PMID- 22994853
TI  - Synthesis and anticonvulsant activity evaluation of 6-substituted
      [1,2,4]triazolo[3,4-a](tetrazolo[5,1-a])phthalazine derivatives.
AB  - With the aim of finding new anticonvulsant drugs, new 6-substituted
      [1,2,4]triazolo[3,4-a] (tetrazolo[5,1-a]) phthalazine derivatives (1-34) have
      been designed and synthesized. All the compounds were evaluated for their
      anticonvulsant activities using the maximal electroshock test (MES). Most of the
      synthesized compounds exhibited potent anticonvulsant activities in the MES. The
      most promising compound 14 showed significant anticonvulsant activity in MES test
      with ED50 value of 9.3 mg/kg. It displayed a wide margin of safety with
      protective index much higher than the standard drug Carbamazepine. And the
      potency of compound 14 against seizures induced by Pentylenetetrazole, Isoniazid,
      Thiosemicarbazide and 3-Mercaptopropionic acid in the chemical-induced seizure
      tests suggested that compound 14 displayed wide spectrum of activity in several
      models.

PMID- 22994854
TI  - An adolescent boy with urticaria to water: review of current treatments for
      aquagenic urticaria.
AB  - We report the case of an adolescent boy with aquagenic urticaria unresponsive to
      oral antihistamine therapy. We successfully treated his condition by topical
      application of a petrolatum-containing cream as a protective coating. To our
      knowledge, this is the first report showing the use of topical therapy alone to
      treat aquagenic urticaria in a child. Based on the effectiveness, safety profile,
      and ease of use, clinicians may wish to consider this regimen as a first-line
      therapy. 

PMID- 22994855
TI  - Oral health care during pregnancy: four aims may be too many.

PMID- 22994856
TI  - Antiepileptic drugs and suicidality: an expert consensus statement from the Task
      Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology.
AB  - In 2008, the U.S. Food and Drug Administration (FDA) issued an alert to health
      care professionals about an increased risk of suicide ideation and suicide
      behavior in people treated with antiepileptic drugs (AEDs). Since then, a number
      of retrospective cohort and case-control studies have been published that are
      trying to address this issue, but gathered results are contradictory. This report
      represents an expert consensus statement developed by an ad hoc task force of the
      Commission on Neuropsychobiology of the International League Against Epilepsy
      (ILAE). Although some (but not all) AEDs can be associated with treatment
      emergent psychiatric problems that can lead to suicidal ideation and behavior,
      the actual suicidal risk is yet to be established, but it seems to be very low.
      The risk of stopping AEDs or refusing to start AEDs is significantly worse and
      can actually result in serious harm including death to the patient. Suicidality
      in epilepsy is multifactorial, and different variables are operant. Clinicians
      should investigate the existence of such risk factors and adopt appropriate
      screening instruments. If necessary, patients should be referred for a
      psychiatric evaluation, but AED treatment should not be withheld, even in
      patients with positive suicidal risks. When starting an AED or switching from one
      to other AEDs, patients should be advised to report to their treating physician
      any change in mood and suicidal ideation. Data on treatment-emergent psychiatric
      adverse events need to be collected, in addition to general safety information,
      during controlled studies in order to have meaningful information for patients
      and their relatives when a new drug is marketed.

PMID- 22994857
TI  - Altrenogest treatment associated with a farrowing induction protocol to avoid
      early parturition in sows.
AB  - This study investigated the effect of altrenogest treatment on the farrowing
      development of sows, and birth weight (BW) and piglet survival until the third
      day of life. Three control groups were used: (i) sows that farrowed spontaneously
      before 114 day of gestation (CONT <114); (ii) sows that spontaneously farrowed at
      >=114 day of gestation (CONT >=114); (iii) sows that farrowed at >=114 day with
      cloprostenol treatment (CONTCLOPR). Other sows were treated with altrenogest
      (Regumate((r)) ) for 3 days (days 111, 112 and 113 of gestation): one group gave
      birth spontaneously (ALT) and the other group received altrenogest until day 113
      and cloprostenol on day 114 (ALTCLOPR). There were no differences (p > 0.05) in
      farrowing duration, BW, coefficient of variation (CV) of BW, stillborn piglets,
      mummified foetuses, percentage of light piglets and survival until Day 3 between
      sows with and without cloprostenol treatment, in both control (CONT >=114 vs
      CONTCLOPR) and altrenogest-treated sows (ALT vs ALTCLOPR). Further comparisons
      were performed taking into account three groups: sows with early delivery (CONT
      <114 - farrowing before 114 days of gestation; n = 56), sows with longer
      gestation (CONT >=114 - with and without cloprostenol treatment sows; n = 103)
      and ALT sows (with and without cloprostenol treatment; n = 105). Gestation length
      of CONT >=114 and ALT sows was similar (p > 0.05), but higher than in CONT <114
      sows. There were no differences (p > 0.05) between groups in farrowing duration,
      CV of BW, and percentages of stillborn piglets and mummified foetuses. Sows of
      CONT <114 group had a larger litter size and a lower BW than sows of the other
      two groups (p < 0.05). Sows of CONT <114 group had a higher percentage of lighter
      piglets and a lower piglet survival rate (p < 0.05) than ALT sows. In conclusion,
      altrenogest treatment proved to be an efficient method to avoid early parturition
      in 3-5 parity sows resulting in heavier piglets at birth.

PMID- 22994858
TI  - Trauma-related bleeding complications in South African patients with haemophilia.

PMID- 22994859
TI  - A review of the effects of moisturizers on the appearance of scars and striae.
AB  - Scars are well known to have a stratum corneum (SC) that is malfunctional.
      Increases in transepidermal water loss and decreases in SC capacitance and
      conductance have been reported. Occlusion therapy is a well-known route to
      improving the signs and symptoms of scarring. Until recently that has been
      assumed to be totally pressure related. However, studies have demonstrated that
      the direct effects of hydration on keratinocytes and fibroblasts contribute to
      the reduction in hypertrophic scarring. Now it is well known that occlusion can
      regulate epidermal cytokine and growth factor production; changes in profibrotic
      and anti-fibrotic factors have been established. As a result, it is to be
      expected that moisturizers may improve the signs and symptoms of scars. As striae
      have been suggested to be anatomically similar to scars and as it is well
      established that paracrine signalling occurs in skin, it is expected that striae
      have similar SC issues. While one cannot exclude the effects of some of the
      ingredients used in the products, several studies are reported in this review
      that demonstrates that moisturization is a key component to reducing the clinical
      signs and symptoms of scars and striae. This is a good example of how knowledge
      of corneobiology leads to corneotherapies for these skin condition problems. The
      review is being written in memory of Professor Johann Wiechers who, before he
      died tragically in November 2011, performed two of the reported studies together
      with colleagues.

PMID- 22994860
TI  - Protein kinase Cbeta is critical for the metabolic switch to glycolysis following
      B-cell antigen receptor engagement.
AB  - Signals derived from the BCR (B-cell antigen receptor) control survival,
      development and antigenic responses. One mechanism by which BCR signals may
      mediate these responses is by regulating cell metabolism. Indeed, the
      bioenergetic demands of naive B-cells increase following BCR engagement and are
      characterized by a metabolic switch to aerobic glycolysis; however, the
      signalling pathways involved in this metabolic reprogramming are poorly defined.
      The PKC (protein kinase C) family plays an integral role in B-cell survival and
      antigenic responses. Using pharmacological inhibition and mice deficient in
      PKCbeta, we demonstrate an essential role of PKCbeta in BCR-induced glycolysis in
      B-cells. In contrast, mice deficient in PKCdelta exhibit glycolytic rates
      comparable with those of wild-type B-cells following BCR cross-linking. The
      induction of several glycolytic genes following BCR engagement is impaired in
      PKCbeta-deficient B-cells. Moreover, blocking glycolysis results in decreased
      survival of B-cells despite BCR engagement. The results establish a definitive
      role for PKCbeta in the metabolic switch to glycolysis following BCR engagement
      of naive B-cells.

PMID- 22994861
TI  - Physicians' attitudes toward the definition of "death from age-related physical
      debility" in deceased elderly with aspiration pneumonia.
AB  - AIM: Deaths from aspiration pneumonia in elderly patients are occasionally
      considered to be "death from age-related physical debility", because most
      aspiration pneumonias are a result of aging and lead to death without any
      definitive therapy. The aim of the present study was to assess physicians'
      attitudes toward the diagnosis of and actual description of "death from age
      related physical debility" on death certificates for deceased patients with
      aspiration pneumonia. METHODS: This study surveyed 62 Japanese physicians
      including 36 pulmonologists and 26 other physicians who treat patients with
      pneumonia. Their attitudes regarding consideration and actually recorded "death
      from age-related physical debility" for deceased patients with aspiration
      pneumonia were assessed by using anonymous questionnaires, which included the
      decision-making process and the necessity of detailed diagnostic criteria.
      RESULTS: A total of 32 (52%) respondents had considered deceased patients with
      aspiration pneumonia to be "death from age-related physical debility", and 10
      (16%) have actually stated this on the death certificate. Advanced age, bedridden
      status, inability of oral intake and disturbance of consciousness including
      dementia were major factors in their decision-making. A total of 34 (55%) of the
      respondent physicians wanted detailed criteria to be established. CONCLUSIONS:
      Physicians' attitudes toward the definition of "death from age-related physical
      debility" vary a great deal depending on the respondent. The description in death
      certificates therefore might inaccurately reflect the results of current
      mortality statistics in Japan.

PMID- 22994863
TI  - One-year results of the CRISTAL Trial, a randomized comparison of cypher
      sirolimus-eluting coronary stents versus balloon angioplasty for restenosis of
      drug-eluting stents.
AB  - OBJECTIVES:  We compared the efficacy of the Cypher Select (Cordis Corporation,
      Bridgewater, NJ, USA) sirolimus-eluting stent (SES) versus balloon angioplasty
      (BA) in in-stent restenosis (ISR) of Taxus or Taxus Liberte paclitaxel-eluting
      stents (PES; Boston Scientific, Natick, MA, USA) or Cypher/Cypher Select SES.
      BACKGROUND: Optimal treatment strategies have not been identified for drug
      eluting stent (DES) ISR. METHODS: Patients with a native coronary artery SES or
      PES ISR were randomized to SES or BA. In addition, a control group included BMS
      ISR treated with SES. Angiographic control was performed at 12 months. RESULTS:
      281 patients were enrolled. Significant differences favoring SES over BA were
      noted in immediate and net gain (1.39 +/- 0.51 vs. 0.97 +/- 0.54 mm, P < 0.0001
      and 1.07 +/- 0.69 vs. 0.49 +/- 0.67 mm, P < 0.0001), 12-month mean luminal
      diameter (MLD; 2.14 +/- 0.62 vs. 1.71 +/- 0.55 mm, P < 0.0001) and percent
      diameter stenosis (%DS; 21 +/- 19.24 vs. 29.82 +/- 18.47, P = 0.001). There was
      no significant difference at 12 months between SES and BA in the primary end
      point late lumen loss (LLL; 0.37 +/- 0.57 vs.0.41 +/- 0.63, P = 0.73) and in in
      stent binary restenosis (11.1% vs. 14%, P = 0.59). Target-lesion
      revascularization (TLR) was numerically lower in patients treated with SES (5.9%
      vs. 13.1%, P = 0.097). There was no difference according to the initial DES. In
      contrast, significantly higher immediate and net gains and MLD were noted in the
      BMS control group treated by SES. CONCLUSIONS: In this angiographic randomized
      trial comparing SES and BA in SES or PES restenosis, 12 month MLD, immediate and
      net gain, and %DS favored SES whereas no difference was noted in LLL. Condensed
      abstract optimal treatment strategies have not been identified for sirolimus
      (SES) or paclitaxel-eluting stent (PES) in-stent restenosis (ISR). We randomized
      patients with a native coronary artery SES or PES ISR to SES or BA. In addition,
      a control group included BMS ISR treated with SES. There was no difference in the
      primary end-point, late lumen loss (LLL) at 12 months between the SES and BA
      groups. However, follow-up MLD and immediate and net gain favored SES.

PMID- 22994862
TI  - Risk factors for end-stage kidney disease after pediatric liver transplantation.
AB  - Adult liver transplant (LT) recipients commonly develop advanced kidney disease.
      However, burden of end-stage kidney disease (ESKD) after pediatric LT has not
      been well-described. We performed a retrospective cohort study of pediatric LTs
      in the United States from 1990 to 2010. Multivariable Cox regression models were
      fit to determine risk factors for ESKD and death. Eight thousand nine hundred
      seventy six children received LTs. During median follow-up of 7.8 years, 2005
      (22%) subjects died (mortality rate 26.1 cases/1000 person-years); 167 (2%)
      developed ESKD (incidence rate 2.2 cases/1000 person-years). Risk factors for
      ESKD included older age at LT (highest risk age >15 vs. < 5 years, HR = 4.94, p <
      0.001), hepatitis C (HR 2.79, p = 0.004), liver re-transplant (HR 2.67, p <
      0.001), eGFR pre-LT < 60 versus >= 60 (HR 2.37, p < 0.001), hepatitis B (HR 2.25,
      p = 0.027), black race (HR 1.46, p = 0.046), and male sex (HR 1.44, p = 0.022).
      LT recipients with ESKD had increased risk of mortality (HR 2.37, p < 0.001).
      Among pediatric LT recipients, rate of ESKD was lower than among adults and far
      exceeded by rate of death, however follow-up time in this study may underestimate
      lifetime burden of ESKD. Although uncommon, ESKD was highly associated with
      mortality. Pediatric LT recipients should be routinely monitored for kidney
      disease, particularly those at highest risk of ESKD.

PMID- 22994864
TI  - The role of basic health insurance on depression: an epidemiological cohort study
      of a randomized community sample in northwest China.
AB  - BACKGROUND: Little research has focused on the relationship between health
      insurance and mental health in the community. The objective of this study is to
      determine how the basic health insurance system influences depression in
      Northwest China. METHODS: Participants were selected from 32 communities in two
      northwestern Chinese cities through a three-stage random sampling. Three waves of
      interviews were completed in April 2006, December 2006, and January 2008. The
      baseline survey was completed by 4,079 participants. Subsequently, 2,220
      participants completed the first follow-up, and 1,888 completed the second follow
      up. Depression symptoms were measured by the Center for Epidemiologic Studies
      Depression Scale (CES-D). RESULTS: A total of 40.0% of participants had at least
      one form of health insurance. The percentages of participants with severe
      depressive symptoms in the three waves were 21.7%, 22.0%, and 17.6%. Depressive
      symptoms were found to be more severe among participants without health insurance
      in the follow-up surveys. After adjusting for confounders, participants without
      health insurance were found to experience a higher risk of developing severe
      depressive symptoms than participants with health insurance (7 months: OR, 1.40;
      95% CI, 1.09-1.82; p = 0.01; 20 months: OR, 1.89; 95% CI, 1.37-2.61; p < 0.001).
      CONCLUSION: A lack of basic health insurance can dramatically increase the risk
      of depression based on northwestern Chinese community samples.

PMID- 22994866
TI  - Ethics education in research involving human beings in undergraduate medicine
      curriculum in Brazil.
AB  - INTRODUCTION: The Brazilian national curriculum guidelines for undergraduate
      medicine courses inspired and influenced the groundwork for knowledge
      acquisition, skills development and the perception of ethical values in the
      context of professional conduct. OBJECTIVE: The evaluation of ethics education in
      research involving human beings in undergraduate medicine curriculum in Brazil,
      both in courses with active learning processes and in those with traditional
      lecture learning methodologies. METHODS: Curricula and teaching projects of 175
      Brazilian medical schools were analyzed using a retrospective historical and
      descriptive exploratory cohort study. Thirty one medical schools were excluded
      from the study because of incomplete information or a refusal to participate.
      Active research for information from institutional sites and documents was guided
      by terms based on 69 DeCS/MeSH descriptors. Curriculum information was correlated
      with educational models of learning such as active learning methodologies,
      tutorial discussions with integrated curriculum into core modules, and
      traditional lecture learning methodologies for large classes organized by
      disciplines and reviewed by occurrence frequency of ethical themes and average
      hourly load per semester. RESULTS: Ninety-five medical schools used traditional
      learning methodologies. The ten most frequent ethical themes were: 1--ethics in
      research (26); 2--ethical procedures and advanced technology (46); 3--ethic
      professional conduct (413). Over 80% of schools using active learning
      methodologies had between 50 and 100 hours of scheduled curriculum time devoted
      to ethical themes whereas more than 60% of traditional learning methodology
      schools devoted less than 50 hours in curriculum time to ethical themes.
      CONCLUSION: The data indicates that medical schools that employ more active
      learning methodologies provide more attention and time to ethical themes than
      schools with traditional discipline-based methodologies. Given the importance of
      ethical issues in contemporary medical education, these findings are significant
      for curriculum change and modification plans in the future of Brazilian medical
      education.

PMID- 22994867
TI  - ERP evidence for the recognition of emotional prosody through simulated cochlear
      implant strategies.
AB  - BACKGROUND: Emotionally salient information in spoken language can be provided by
      variations in speech melody (prosody) or by emotional semantics. Emotional
      prosody is essential to convey feelings through speech. In sensori-neural hearing
      loss, impaired speech perception can be improved by cochlear implants (CIs). Aim
      of this study was to investigate the performance of normal-hearing (NH)
      participants on the perception of emotional prosody with vocoded stimuli.
      Semantically neutral sentences with emotional (happy, angry and neutral) prosody
      were used. Sentences were manipulated to simulate two CI speech-coding
      strategies: the Advance Combination Encoder (ACE) and the newly developed
      Psychoacoustic Advanced Combination Encoder (PACE). Twenty NH adults were asked
      to recognize emotional prosody from ACE and PACE simulations. Performance was
      assessed using behavioral tests and event-related potentials (ERPs). RESULTS:
      Behavioral data revealed superior performance with original stimuli compared to
      the simulations. For simulations, better recognition for happy and angry prosody
      was observed compared to the neutral. Irrespective of simulated or unsimulated
      stimulus type, a significantly larger P200 event-related potential was observed
      for happy prosody after sentence onset than the other two emotions. Further, the
      amplitude of P200 was significantly more positive for PACE strategy use compared
      to the ACE strategy. CONCLUSIONS: Results suggested P200 peak as an indicator of
      active differentiation and recognition of emotional prosody. Larger P200 peak
      amplitude for happy prosody indicated importance of fundamental frequency (F0)
      cues in prosody processing. Advantage of PACE over ACE highlighted a privileged
      role of the psychoacoustic masking model in improving prosody perception. Taken
      together, the study emphasizes on the importance of vocoded simulation to better
      understand the prosodic cues which CI users may be utilizing.

PMID- 22994868
TI  - Atmospheric transport and deposition of mineral dust to the ocean: implications
      for research needs.
AB  - This paper reviews our knowledge of the measurement and modeling of mineral dust
      emissions to the atmosphere, its transport and deposition to the ocean, the
      release of iron from the dust into seawater, and the possible impact of that
      nutrient on marine biogeochemistry and climate. Of particular concern is our poor
      understanding of the mechanisms and quantities of dust deposition as well as the
      extent of iron solubilization from the dust once it enters the ocean. Model
      estimates of dust deposition in remote oceanic regions vary by more than a factor
      of 10. The fraction of the iron in dust that is available for use by marine
      phytoplankton is still highly uncertain. There is an urgent need for a long-term
      marine atmospheric surface measurement network, spread across all oceans. Because
      the southern ocean is characterized by large areas with high nitrate but low
      chlorophyll surface concentrations, that region is particularly sensitive to the
      input of dust and iron. Data from this region would be valuable, particularly at
      sites downwind from known dust source areas in South America, Australia, and
      South Africa. Coordinated field experiments involving both atmospheric and marine
      measurements are recommended to address the complex and interlinked processes and
      role of dust/Fe fertilization on marine biogeochemistry and climate.

PMID- 22994865
TI  - Guiding principles for the care of older adults with multimorbidity: an approach
      for clinicians: American Geriatrics Society Expert Panel on the Care of Older
      Adults with Multimorbidity.

PMID- 22994870
TI  - Memory lessons from the courtroom: Reflections on being a memory expert on the
      witness stand.
AB  - In the first part of this article I describe a variety of cases that I have been
      involved with that led to my becoming an expert witness. These cases range from
      questions about children's memory for being raped, to remembering an ear
      witnessed murder, to preventing future false memories. In the second part of this
      article I reflect on some of the remarkable feats of remembering that
      complainants exhibit in court, ones that contradict much of what the scientific
      study of memory has shown to be true. Along the way I argue that until this
      scientific knowledge becomes part of a "culture of memory" familiar to triers of
      fact (judges, jurors), police, and laypeople, memory experts will continue to be
      an inexorable part of the legal process when memory serves as the main or only
      evidence.

PMID- 22994869
TI  - Need of minimal important difference for oral health-related quality of life
      measures.
AB  - Demand and use for oral health-related quality of life (OHRQoL) instruments have
      increased in recent years in both research and clinical settings. These
      instruments can be used to measure patient's health status or detect changes in a
      patient's health status in response to an intervention or changes in disease
      trajectory. Ensuring universal acceptance of these measures requires easy
      interpretation of its scores for clinicians, researchers, and patients. The most
      important way of describing and interpreting this significance of changes in
      OHRQoL is through the establishment of minimal important difference (MID). The
      minimally important difference represents the smallest improvement considered
      worthwhile by a patient. A comprehensive search of published literature
      identified only 12 published articles on establishment of MID for OHRQoL
      measures. This scarcity of published studies on MID encourages the need of
      appropriate interpretation and describing patient satisfaction in reference to
      that treatment using MID. Anchor- and distribution-based methods are the two
      general approaches that have been proposed and recommended to interpret
      differences or changes in OHRQoL. Both of these methods of determining the MID
      have specific shortcomings; therefore, it is proposed to adopt triangulation
      approaches in which the methods are combined. The objective of this review is to
      summarize the need for, importance of, and recommendations for methods of
      establishing MID for OHRQoL measures. 

PMID- 22994871
TI  - Low doses of exogenous interferon-gamma attenuated airway inflammation through
      enhancing Fas/FasL-induced CD4+ T cell apoptosis in a mouse asthma model.
AB  - To investigate whether low doses of exogenous interferon (IFN)-gamma attenuate
      airway inflammation, and the underlying mechanisms, in asthma. C57BL/6 mice
      (n=42), after intraperitoneal ovalbumin (OVA) sensitization on day 0 and day 12,
      were challenged with OVA aerosol for 6 consecutive days. Different doses of IFN
      gamma were then administered intraperitoneally 5 min before each inhalation
      during OVA challenge. Airway hyperresponsiveness, airway inflammatory cells,
      cytokine profiles, and Fas/FasL expression on CD4(+) T cells were evaluated in an
      asthma model. The effect of various IFN-gamma doses on Fas/FasL expression and
      CD4(+) T cell apoptosis were assessed in vitro. We demonstrated that low doses of
      IFN-gamma reduced pulmonary infiltration of inflammatory cells, Th2 cytokine
      production, and goblet cells hyperplasia (P<0.05), while high doses of endogenous
      IFN-gamma had almost no effect. We also found that low doses of IFN-gamma
      relocated Fas/FasL to the CD4(+) T cell surface in the asthma model (P<0.05) and
      increased FasL-induced apoptosis in vitro (P<0.05). Furthermore, treatment with
      MFL-3, an anti-FasL antibody, partially abolished the anti- inflammatory
      properties of IFN-gamma in the airway rather than affecting the Th1/Th2 balance.
      This research has revealed an alternative mechanism in asthma that involves low
      doses of IFN-gamma, which attenuate airway inflammation through enhancing
      Fas/FasL-induced CD4(+) T cell apoptosis.

PMID- 22994873
TI  - Adaptive immunity rather than viral cytopathology mediates polyomavirus
      associated nephropathy in mice.

PMID- 22994872
TI  - Toll-like receptor 5 engagement induces interleukin-17C expression in intestinal
      epithelial cells.
AB  - The family of interleukin-17 (IL-17) cytokine is the essential inflammatory
      mediator that influences the pathophysiology of various inflammatory diseases.
      Many studies focused on investigating the expression, signaling, and biological
      impacts of IL-17A and IL-17F, and the neutralization of these cytokines exhibited
      some promising results in clinical trials. In contrast, the expression resources
      and physiological relevance of IL-17C remained to be studied. In this study,
      through a microarray approach conducted with nontransformed human colonic
      epithelial cells (NCM460), we found that bacterial flagellin stimulation elicited
      potent IL-17C mRNA expression. We also confirmed that IL-17C protein production
      was strongly induced by flagellin in these cells. Flagellin-induced IL-17C
      expression was also observed in human colon adenocarcinoma cells such as DLD-1
      and HT-29, indicating that IL-17C could be a signature inflammatory cytokine from
      intestinal epithelial cells in response to flagellin. Since inhibited in TLR5-,
      or MyD88- or TRIF-silenced cells, flagellin-induced IL-17C expression was
      specifically mediated by TLR5 and, subsequently, MyD88 and TRIF adaptor
      molecules. Furthermore, in line with inflammatory nature of IL-17, we found that
      IL-17C expression was substantially enhanced in the intestinal tissues from
      Ulcerative colitis patients. Given the facts that TLR5 is a key pattern
      recognition receptor which mediates microbial recognition in the intestinal
      epithelium and IL-17C turned out to be a unique member of the IL-17 family
      expressed in intestinal epithelial cells on TLR5 activation, our study may
      provide an important clue on understanding how intestinal microbes would
      contribute to an inflammatory program in the gut.

PMID- 22994874
TI  - Similar survival 15 years after coronary artery surgery irrespective of left main
      stem stenosis.
AB  - OBJECTIVES: To evaluate 15-year survival after coronary artery bypass grafting
      (CABG) in relation to grade left main stenosis (LMS) and right coronary artery
      (RCA) obstruction. DESIGN: Coronary angiographic findings were prospectively
      collected in 977 patients who had CABG for stable angina during 1994-1995 and
      were included in the Swedish Coronary Revascularization - Swedish Council of
      Technology Assessment study. RESULTS: Significant LMS was present in one fifth of
      the patients and significant RCA obstruction was found in 61% of those with LMS
      and in 68% of patients without LMS. The patients were categorized as no LMS
      (Group I), LMS without RCA obstruction (Group II) or significant LMS with
      significant right coronary artery (RCA) obstruction (Group III). Early mortality
      did not differ in the three groups and was 1.2, 1.2% and 0.8% in group I, II and
      III, respectively. Corresponding survival at 15 years was similar 51%, 47% and
      47%, respectively. In multivariable analysis older age, smoking, severe angina,
      positive stress test, hypertension, diabetes mellitus and ejection fraction < 50%
      were risk factors for death at 15 years. CONCLUSIONS: Death 15 years after CABG
      correlated to clinical variables but was not predicted from presence of LMS with
      or without significant associated RCA obstruction.

PMID- 22994875
TI  - Tighter control of postprandial hyperglycemia with mitiglinide/voglibose fixed
      dose combination in Japanese patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: The objective of this study was to compare the effects of mitiglinide,
      voglibose and its combination on metabolic responses after a test meal in
      Japanese patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND
      METHODS: This randomized crossover study consisted of four periods between August
      and November 2011. In the first period, all patients (n = 12) received water
      alone (control period). In the next three periods, the patients received 10 mg
      mitiglinide, 0.2 mg voglibose or a combination in a random order. MAIN OUTCOME
      MEASURES: Postprandial metabolite/hormone levels were then measured. RESULTS:
      Plasma glucose and serum insulin reached peak levels by 60 - 90 and 90 min,
      respectively, after the test meal in the control group. The combination reduced
      postprandial glucose levels compared with mitiglinide or voglibose alone,
      particularly at 30 - 90 min, which significantly exceeded the effects of
      mitiglinide (p < 0.05). Mitiglinide and the combination restored early insulin
      response, whereas the combination provided an insulin-sparing effect compared
      with mitiglinide alone. The combination improved postprandial lipid profiles,
      combining the effects of both drugs. CONCLUSION: This study revealed marked
      differences in the postprandial metabolic effects of mitiglinide, voglibose and
      its combination in patients with T2DM. The combination therapy should enable
      tighter control of postprandial hyperglycemia compared with the individual drugs.

PMID- 22994876
TI  - Improving access to eye health services in rural Timor-Leste.
AB  - CONTEXT: Delivering eye health services to people in rural areas, especially in
      fragile, post-conflict countries, is a major challenge. This article reports on
      the implementation and evaluation of an innovative district-based outreach
      service. The main project partners were the Timor-Leste Ministry of Health and an
      international non-government organization, with assistance from a local non
      government organization. ISSUE: An eye care nurse in Covalima District, a remote
      location 178 km from Timor-Leste's capital, Dili, was provided with a motor-bike
      for transport and regular support for outreach eye services to sub-district
      facilities. Data collected over the first year of operation were examined and
      included: services provided, spectacles dispensed, health promotion activities
      conducted and the cost of providing these. The project was also evaluated for its
      relevance, effectiveness, efficiency, impact and sustainability. LESSONS LEARNED:
      In the first 12 months, 55 outreach visits were conducted across the district's
      seven sub-districts during which 1405 people received vision screening, and 777
      spectacles were dispensed. In addition to meeting the five evaluation criteria,
      compared with the hospital-based eye clinic the outreach service resulted in
      significantly greater gender equity among eye health service beneficiaries. This
      pilot project demonstrates what can be achieved when a Ministry of Health
      (central and district level) and non-government organizations (international and
      local) work in partnership to support a dedicated health care provider.

PMID- 22994878
TI  - Revascularization for a necrotic immature permanent lateral incisor: a case
      report and literature review.
AB  - BACKGROUND: Revascularization is a valuable treatment in immature necrotic teeth
      that allows the continuation of root development. CASE REPORT: This article
      describes the successful revascularization treatment of an immature maxillary
      lateral incisor that was initially diagnosed with apical periodontitis. The tooth
      was asymptomatic and functional clinically and radiographically during the follow
      up period of 5 years. CONCLUSION: The follow-up showed evidence of progressive
      thickening of the dentinal walls, development of root length and apical closure.
      The article also discusses the currently available literature regarding
      revascularization of immature permanent teeth.

PMID- 22994877
TI  - Acute diesel exhaust particle exposure increases viral titre and inflammation
      associated with existing influenza infection, but does not exacerbate deficits in
      lung function.
AB  - BACKGROUND: Exposure to diesel exhaust particles (DEP) is thought to exacerbate
      many pre-existing respiratory diseases, including asthma, bronchitis and chronic
      obstructive pulmonary disease, however, there is a paucity of data on whether DEP
      exacerbates illness due to respiratory viral infection. OBJECTIVES: To assess the
      physiological consequences of an acute DEP exposure during the peak of influenza
      induced illness. METHODS: We exposed adult female BALB/c mice to 100 MUg DEP (or
      control) 3.75 days after infection with 10(4.5) plaque forming units of influenza
      A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we
      measured thoracic gas volume and lung function at functional residual capacity.
      Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and
      cytokines, and whole lungs were taken for measurement of viral titre. RESULTS:
      Influenza infection resulted in significantly increased inflammation, cytokine
      influx and impairment to lung function. DEP exposure alone resulted in less
      inflammation and cytokine influx, and no impairment to lung function. Mice
      infected with influenza and exposed to DEP had higher viral titres and
      neutrophilia compared with infected mice, yet they did not have more impaired
      lung mechanics than mice infected with influenza alone. CONCLUSIONS: A single
      dose of DEP is not sufficient to physiologically exacerbate pre-existing
      respiratory disease caused by influenza infection in mice.

PMID- 22994879
TI  - Multivariate outcome prediction in traumatic brain injury with focus on
      laboratory values.
AB  - Traumatic brain injury (TBI) is a major cause of morbidity and mortality.
      Identifying factors relevant to outcome can provide a better understanding of TBI
      pathophysiology, in addition to aiding prognostication. Many common laboratory
      variables have been related to outcome but may not be independent predictors in a
      multivariate setting. In this study, 757 patients were identified in the
      Karolinska TBI database who had retrievable early laboratory variables. These
      were analyzed towards a dichotomized Glasgow Outcome Scale (GOS) with logistic
      regression and relevance vector machines, a non-linear machine learning method,
      univariately and controlled for the known important predictors in TBI outcome:
      age, Glasgow Coma Score (GCS), pupil response, and computed tomography (CT)
      score. Accuracy was assessed with Nagelkerke's pseudo R2. Of the 18 investigated
      laboratory variables, 15 were found significant (p<0.05) towards outcome in
      univariate analyses. In contrast, when adjusting for other predictors, few
      remained significant. Creatinine was found an independent predictor of TBI
      outcome. Glucose, albumin, and osmolarity levels were also identified as
      predictors, depending on analysis method. A worse outcome related to increasing
      osmolarity may warrant further study. Importantly, hemoglobin was not found
      significant when adjusted for post-resuscitation GCS as opposed to an admission
      GCS, and timing of GCS can thus have a major impact on conclusions. In total,
      laboratory variables added an additional 1.3-4.4% to pseudo R2.

PMID- 22994880
TI  - Metabolic hormones in saliva: origins and functions.
AB  - The salivary proteome consists of thousands of proteins, which include, among
      others, hormonal modulators of energy intake and output. Although the functions
      of this prominent category of hormones in whole body energy metabolism are well
      characterized, their functions in the oral cavity, whether as a salivary
      component, or when expressed in taste cells, are less studied and poorly
      understood. The respective receptors for the majority of salivary metabolic
      hormones have been also shown to be expressed in salivary glands (SGs), taste
      cells, or other cells in the oral mucosa. This review provides a comprehensive
      account of the gastrointestinal hormones, adipokines, and neuropeptides
      identified in saliva, SGs, or lingual epithelium, as well as their respective
      cognate receptors expressed in the oral cavity. Surprisingly, few functions are
      assigned to salivary metabolic hormones, and these functions are mostly
      associated with the modulation of taste perception. Because of the well
      characterized correlation between impaired oral nutrient sensing and increased
      energy intake and body mass index, a conceptually provocative point of view is
      introduced, whereupon it is argued that targeted changes in the composition of
      saliva could affect whole body metabolism in response to the activation of
      cognate receptors expressed locally in the oral mucosa. 

PMID- 22994882
TI  - Very low and low birth weight associated with maternal periodontitis.
AB  - AIM: The aim of this study was to evaluate the association of very low and low
      birth weight (VLBW and LBW) with maternal periodontitis. MATERIAL AND METHODS:
      Overall, 1206 women were examined at post-partum and two alternative criteria for
      periodontitis definition were used: (1) four or more teeth with at least one site
      with probing depth (PD) >= 4 mm and clinical attachment loss (CAL) >= 3 mm; and
      (2) at least one site with PD and CAL >= 4 mm. For each definition, two
      multivariate analyses were performed: (1) linear regression for birth weight; (2)
      ordinal logistic regression for birth weight, categorized as adequate (n = 1046),
      LBW (n = 145) and VLBW (n = 15). RESULTS: Linear regression showed that maternal
      periodontitis was associated with a decrease in mean birth weight (periodontitis
      definition 1: p = 0.027; periodontitis definition 2: p = 0.003). Ordinal logistic
      regression showed that maternal periodontitis was associated with LBW and VLBW
      [odds ratio (OR) = 2.0; 95% confidence interval (CI) 1.39-2.90, when considering
      periodontitis definition 2]; and with LBW (OR = 1.65; 95% CI 1.15-2.36, when
      considering periodontitis definition 1). CONCLUSION: Maternal periodontitis was
      associated with a decrease in mean birth weight, as well as with LBW and VLBW.

PMID- 22994883
TI  - A hierarchical semiparametric model for incorporating intergene information for
      analysis of genomic data.
AB  - For analysis of genomic data, e.g., microarray data from gene expression
      profiling experiments, the two-component mixture model has been widely used in
      practice to detect differentially expressed genes. However, it naively imposes
      strong exchangeability assumptions across genes and does not make active use of a
      priori information about intergene relationships that is currently available,
      e.g., gene annotations through the Gene Ontology (GO) project. We propose a
      general strategy that first generates a set of covariates that summarizes the
      intergene information and then extends the two-component mixture model into a
      hierarchical semiparametric model utilizing the generated covariates through
      latent nonparametric regression. Simulations and analysis of real microarray data
      show that our method can outperform the naive two-component mixture model.

PMID- 22994881
TI  - The sacroiliac joint: an overview of its anatomy, function and potential clinical
      implications.
AB  - This article focuses on the (functional) anatomy and biomechanics of the pelvic
      girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for
      effective load transfer between the spine and legs. The sacrum, pelvis and spine,
      and the connections to the arms, legs and head, are functionally interrelated
      through muscular, fascial and ligamentous interconnections. A historical overview
      is presented on pelvic and especially SIJ research, followed by a general
      functional anatomical overview of the pelvis. In specific sections, the
      development and maturation of the SIJ is discussed, and a description of the bony
      anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on
      the SIJ ligaments and innervation is discussed, followed by a section on the
      pathology of the SIJ. Pelvic movement studies are investigated and biomechanical
      models for SIJ stability analyzed, including examples of insufficient versus
      excessive sacroiliac force closure.

PMID- 22994884
TI  - Identification and quantification of oligodendrocyte precursor cells in multiple
      system atrophy, progressive supranuclear palsy and Parkinson's disease.
AB  - Multiple system atrophy is a neurodegenerative disorder characterized
      pathologically by abnormal accumulations of alpha-synuclein in the cytoplasm of
      oligodendrocytes, which are termed glial cytoplasmic inclusions (GCIs).
      Oligodendrocytes are responsible for myelinating axons and providing neurotrophic
      support, but in MSA, myelin loss, axonal loss and gliosis are consistent features
      suggesting that GCIs play a central role in disease pathogenesis.
      Oligodendroglial, myelin and axonal degeneration are also features of multiple
      sclerosis (MS) in which recent studies have highlighted the robust remyelination
      capacity of the central nervous system (CNS). The cells responsible for
      remyelination are called oligodendroglial precursor cells (OPCs). In this study,
      we investigated the role of OPCs in the pathogenesis of MSA and progressive
      supranuclear palsy (PSP), a neurodegenerative disease in which neuropathological
      changes include oligodendroglial inclusions composed of microtubule-associated
      protein tau. Despite the lability of OPC-specific antigens, we successfully
      identified OPCs and demonstrated that tau and alpha-synuclein do not accumulate
      in OPCs. We also showed that the density of OPCs was increased in a white matter
      region of the MSA brain, which is also severely affected by GCIs and myelin
      degeneration. These findings raise the possibility that OPCs could be available
      to repair disease-associated damage in MSA, consistent with their biological
      function.

PMID- 22994885
TI  - Insomnia and urban neighbourhood contexts--are associations modified by
      individual social characteristics and change of residence? Results from a
      population-based study using residential histories.
AB  - BACKGROUND: Until now, insomnia has not been much of interest in epidemiological
      neighbourhood studies, although literature provides evidence enough for insomnia
      related mechanisms being potentially dependent on neighbourhood contexts.
      Besides, studies have shown differences in sleep along individual social
      characteristics that might render residents more vulnerable to neighbourhood
      contextual exposures. Given the role of exposure duration and changes in the
      relationship between neighbourhoods and health, we studied associations of
      neighbourhood unemployment and months under residential turnover with insomnia by
      covering ten years of residential history of nearly 3,000 urban residents in the
      Ruhr Area, Germany. METHODS: Individual data were retrieved from the Heinz
      Nixdorf Recall Study, a population-based study of randomly chosen participants
      from adjacent cities, which contains self-rated insomnia symptoms and individual
      social characteristics. Participants' residential addresses were retrospectively
      assessed using public registries. We built individually derived exposure measures
      informing about mean neighbourhood unemployment rates and months under high
      residential turnover. These measures were major predictors in multivariate
      logistic regressions modelling the association between social neighbourhood
      characteristics and insomnia in the whole sample and subgroups defined by low
      income, low education, social isolation, and change of residence. Traffic-related
      noise, age, gender, economic activity, and education were considered as
      covariates. RESULTS: Nearly 12 per cent of the participants complained about
      insomnia. Associations of neighbourhood unemployment with insomnia were more
      consistent than those of residential turnover in the whole sample (adjusted OR
      1.42, 95% CI 1.00-2.03 for neighbourhood unemployment and OR 1.33, 95% CI 0.78
      2.25 for residential turnover in the highest exposure categories). In low-income
      and socially isolated participants, neighbourhood unemployment odds of reporting
      insomnia were particularly elevated (adjusted OR 2.90, 95% CI 1.39-6.02 and OR
      3.32, 95% CI 1.11-9.96, respectively). Less educated participants displayed
      relatively high odds of reporting insomnia throughout all upper neighbourhood
      unemployment exposure categories. Change of residence weakened associations,
      whereas undisrupted exposure sharpened them by trend. CONCLUSIONS: Our findings
      hint at multiple stressors being effective in both the neighbourhood context and
      individual resident, possibly reflecting precarious life situations undermining
      residents' sleep and health chances. Moreover, our results suggest a temporal
      dependency in the association between neighbourhood and insomnia.

PMID- 22994886
TI  - Research integrity in greater China: surveying regulations, perceptions and
      knowledge of research integrity from a Hong Kong perspective.
AB  - In their 2010 article 'Research Integrity in China: Problems and Prospects', Zeng
      and Resnik challenge others to engage in empirical research on research integrity
      in China. Here we respond to that call in three ways: first, we provide updates
      to their analysis of regulations and allegations of scientific misconduct;
      second, we report on two surveys conducted in Hong Kong that provide empirical
      backing to describe ways in which problems and prospects that Zeng and Resnik
      identify are being explored; and third, we continue the discussion started by
      Zeng and Resnik, pointing to ways in which China's high-profile participation in
      international academic research presents concerns about research integrity.
      According to our research, based upon searches of both English and Chinese
      language literature and policies, and two surveys conducted in Hong Kong,
      academic faculty and research post-graduate students in Hong Kong are aware of
      and have a positive attitude towards responsible conduct of research. Although
      Hong Kong is but one small part of China, we present this research as a response
      to concerns Zeng and Resnik introduce and as a call for a continued conversation.

PMID- 22994887
TI  - Tuberculous dactylitis presenting as paronychia with pseudopterygium and nail
      dystrophy.
AB  - Scrofuloderma is a type of secondary tuberculosis (TB) arising from contiguous
      involvement of skin by an underlying tuberculous focus in the lymph nodes or
      bones. It may occasionally be the presenting feature of osteoarticular TB.
      Tuberculous dactylitis is the involvement of the small tubular bones of the hands
      and feet, and most cases occur in children younger than 6 years of age. Fingers
      are more commonly involved than toes, and painless swelling of a digit is the
      usual presentation. Involvement of the toes is rare, with only a few reported
      cases. The indolent clinical course leads to a delay in diagnosis, and bone
      shortening with joint deformity is the usual outcome, especially in tuberculous
      dactylitis affecting the foot. We report here a case of tuberculous dactylitis of
      the great toe and scrofuloderma affecting the nail fold presenting as painless
      paronychia with pseudopterygium and nail dystrophy. Nail involvement led to an
      early presentation and timely diagnosis and treatment before progression to
      permanent bone or joint deformity.

PMID- 22994888
TI  - Rationing scarce organs for transplantation: healthcare provider perspectives on
      wait-listing and organ allocation.
AB  - Ongoing debate about how to maximize the benefit of scarce organs while
      maintaining equity of access to transplantation exists. This study aims to
      synthesize healthcare provider perspectives on wait-listing and organ allocation.
      MEDLINE, Embase, and PsycINFO were searched till February 21, 2011. Quantitative
      data were extracted, and a qualitative synthesis of the studies was conducted.
      Twenty studies involving 4254 respondents were included. We identified two goals
      underpinning healthcare provider preferences for organ allocation: (i) maximize
      clinical benefit (quality of life gains, patient survival, treatment adherence,
      and graft survival) and social outcomes (social support, productivity, and
      valuation); (ii) achieve equity (waiting time, patient preferences, access to
      live donation, and medical urgency). Maximizing clinical or social outcomes meant
      organs would be preferentially given to patients expected to achieve good
      transplant outcomes or wider social gain. Achieving equity meant all patients
      should have an equal chance of transplant, or patients deemed more urgent receive
      higher priority. A tension between equity and efficiency is apparent. Balanced
      against dimensions of efficiency were considerations to instill a degree of
      perceived fairness in organ allocation. Ongoing engagement with stakeholders is
      needed to enhance transparency, a reasonable balance between efficiency and
      equity, and avoid discrimination against specific populations.

PMID- 22994889
TI  - Silicon nutrition increases grain yield, which, in turn, exerts a feed-forward
      stimulation of photosynthetic rates via enhanced mesophyll conductance and alters
      primary metabolism in rice.
AB  - Silicon (Si) is not considered to be an essential element for higher plants and
      is believed to have no effect on primary metabolism in unstressed plants. In rice
      (Oryza sativa), Si nutrition improves grain production; however, no attempt has
      been made to elucidate the physiological mechanisms underlying such responses.
      Here, we assessed crop yield and combined advanced gas exchange analysis with
      carbon isotope labelling and metabolic profiling to measure the effects of Si
      nutrition on rice photosynthesis, together with the associated metabolic changes,
      by comparing wild-type rice with the low-Si rice mutant lsi1 under unstressed
      conditions. Si improved the harvest index, paralleling an increase in nitrogen
      use efficiency. Higher crop yields associated with Si nutrition exerted a feed
      forward effect on photosynthesis which was fundamentally associated with
      increased mesophyll conductance. By contrast, Si nutrition did not affect
      photosynthetic gas exchange during the vegetative growth phase or in de-grained
      plants. In addition, Si nutrition altered primary metabolism by stimulating amino
      acid remobilization. Our results indicate a stimulation of the source capacity,
      coupled with increased sink demand, in Si-treated plants; therefore, we identify
      Si nutrition as an important target in attempts to improve the agronomic yield of
      rice.

PMID- 22994890
TI  - Prevalence of anemia in Chinese nursing home older adults: implication of age and
      renal impairment.
AB  - AIM: There is little data regarding the prevalence and associated comorbidities
      of anemia in Chinese nursing home older adults. The objective of this study was
      to investigate the prevalence and associated comorbidities of anemia in Chinese
      nursing home older adults. METHODS: We carried out a retrospective cross
      sectional study in nine nursing homes in Hong Kong. The hemoglobin (Hb) level,
      mean corpuscular volume (MCV), serum creatinine and comorbidities data of
      residents were examined. Older adults were regarded as anemic according to the
      World Health Organization criteria (Hb <13 g/dL for men and <12 g/dL for women).
      The glomerular filtration rate (eGFR) was estimated by the Modification of Diet
      in Renal Disease Study (MDRD [Chinese-adjusted]) equation. Patients with chronic
      renal impairment were defined as having eGFR <60 mL/min/1.73 m(2) . RESULTS: A
      total of 812 residents were included (mean age 86.0 +/- 7.6 years). The mean
      hemoglobin was 12.0 +/- 1.8 g/dL in men and 11.4 +/- 1.6g/dL in women. The mean
      eGFR was 75.1 +/- 31.7 mL/min/1.73 m(2) . A total of 67.0% of residents had
      anemia (70.5% in men and 65.2% in women). Anemic older adults were older and had
      a higher prevalence of renal impairment than non-anemic older adults (P<0.001).
      There was no significant difference between the two groups regarding the
      prevalence of other comorbidities. When stratified into different age groups,
      there were significant correlations between anemia and renal impairment in all
      subgroups (age <= 80 years, P<0.05; age 81-90 years, P<0.01; age >90 years,
      P<0.05). The same correlation was found between normocytic anemia and renal
      impairment. Conversely, when stratified according to eGFR (>= 60 mL/min/1.73 m(2)
      vs <60 mL/min/1.73 m(2) ), we did not observe a significant correlation between
      anemia and age group. CONCLUSION: In conclusion, anemia is prevalent in Chinese
      nursing home residents and is strongly associated with renal impairment. Further
      studies of early identification and management of anemia with renal impairment
      are recommended in this population.

PMID- 22994891
TI  - Investigating the structural origin of trpzip2 temperature dependent unfolding
      fluorescence line shape based on a Markov state model simulation.
AB  - Vibrationally resolved fluorescence spectra of the beta-hairpin trpzip2 peptide
      at two temperatures as well as during a T-jump unfolding process are simulated on
      the basis of a combination of Markov state models and quantum chemistry schemes.
      The broad asymmetric spectral line shape feature is reproduced by considering the
      exciton-phonon couplings. The temperature dependent red shift observed in the
      experiment has been attributed to the state population changes of specific
      chromophores. Through further theoretical study, it is found that both the
      environment's electric field and the chromophores' geometry distortions are
      responsible for tryptophan fluorescence shift.

PMID- 22994892
TI  - Mutations in the essential FAS II beta-hydroxyacyl ACP dehydratase complex confer
      resistance to thiacetazone in Mycobacterium tuberculosis and Mycobacterium
      kansasii.
AB  - It has recently been shown that the anti-mycobacterial pro-drug thiacetazone
      (TAC) inhibits the conversion of double bonds of mycolic acid precursors into
      cyclopropyl rings in Mycobacterium bovis var BCG, M. marimum and M. chelonae by
      affecting the cyclopropyl mycolic acid synthases (CMASs) as judged by the build
      up of unsaturated mycolate precursors. In our hands, TAC inhibits mycolic acid
      biosynthesis in Mycobacterium tuberculosis and M. kansasii with almost negligible
      accumulation of those precursors. Our observations that 'de novo' biosynthesis of
      all the mycolic acid families decreased upon TAC treatment prompted us to analyse
      the role of each one of the Type II Fatty Acid Synthase (FASII) enzymes.
      Overexpression of the hadABC operon, encoding the essential FASII dehydratase
      complex, but not of any of the remaining FASII genes acting on the elongation of
      fatty acyl chains leading to the synthesis of meromycolic acids, resulted in high
      level of resistance to TAC in M. tuberculosis. Spontaneous M. tuberculosis and M.
      kansasii TAC-resistant mutants isolated during this work revealed mutations in
      the hadABC genes strongly supporting our proposal that these enzymes are new
      players in the resistance to this anti-mycobacterial compound.

PMID- 22994894
TI  - Object specificity and personal relevance in long-term visual remembering.
AB  - The personal relevance of an object is multi-faceted, each facet being capable of
      contributing to the effects on object memory attributed to personal relevance. An
      object's status as an individual object (object specificity), rather than just a
      category of object, is one such facet and its impact on the long-term visual
      remembering of everyday objects is assessed in two experiments. Images and
      drawings were produced under generic (e.g., "Please draw a bed") and personal
      exemplar (e.g., "Please draw your bed") instructions, and participants indicated
      the degree to which the image on which their drawing was based was of a specific
      object or a generic object. Object specificity induced a sense of time and place
      for a remembered object, the most recent encounter with the object being most
      salient. Other aspects of personal relevance collectively facilitated the
      retrieval of an object's category-irrelevant features (thereby increasing the
      vividness of the object image), the other objects with which it was seen, and a
      more general episodic sense of place. Against a broader theoretical perspective,
      it is proposed that visual episodic memory and visual knowledge are primary
      sources of information for specific personally relevant objects and generic
      objects, respectively.

PMID- 22994893
TI  - Formation and domain partitioning of H-ras peptide nanoclusters: effects of
      peptide concentration and lipid composition.
AB  - Experiments have shown that homologous Ras proteins containing different lipid
      modification, which is required for membrane binding, form nonoverlapping
      nanoclusters on the plasma membrane. However, the physical basis for clustering
      and lateral organization remains poorly understood. We have begun to tackle this
      issue using coarse-grained molecular dynamics simulations of the H-ras lipid
      anchor (tH), a triply lipid-modified heptapeptide embedded in a domain-forming
      mixed lipid bilayer [Janosi L. et al. Proc. Natl. Acad. Sci. U.S.A. 2012, 109,
      8097]. Here we use the same simulation approach to investigate the effect of
      peptide concentration and bilayer composition on the clustering and lateral
      distribution of tH. We found no major difference in the clustering behavior of tH
      above a certain concentration. However, the simulations predict the existence of
      a critical concentration below which tH does not form nanoclusters. Moreover, our
      data demonstrate that cholesterol enhances the stability of tH nanoclusters but
      is not required for their formation. Finally, analyses of peptide distributions
      and partition free energies allowed us to quantitatively describe how clustering
      facilitates the accumulation of tH at the interface between ordered and
      disordered domains of the simulated bilayer systems. These thermodynamic insights
      represent some of the key elements for a comprehensive understanding of the
      molecular basis for the formation and stability of Ras signaling platforms.

PMID- 22994895
TI  - A versatile proline/alanine transporter in the unicellular pathogen Leishmania
      donovani regulates amino acid homoeostasis and osmotic stress responses.
AB  - Unlike all other organisms, parasitic protozoa of the family Trypanosomatidae
      maintain a large cellular pool of proline that, together with the alanine pool,
      serve as alternative carbon sources as well as reservoirs of organic osmolytes.
      These reflect adaptation to their insect vectors whose haemolymphs are
      exceptionally rich in the two amino acids. In the present study we identify and
      characterize a new neutral amino acid transporter, LdAAP24, that translocates
      proline and alanine across the Leishmania donovani plasma membrane. This
      transporter fulfils multiple functions: it is the sole supplier for the
      intracellular pool of proline and contributes to the alanine pool; it is
      essential for cell volume regulation after osmotic stress; and it regulates the
      transport and homoeostasis of glutamate and arginine, none of which are its
      substrates. Notably, we provide evidence that proline and alanine exhibit
      different roles in the parasitic response to hypotonic shock; alanine affects
      swelling, whereas proline influences the rate of volume recovery. On the basis of
      our data we suggest that LdAAP24 plays a key role in parasite adaptation to its
      varying environments in host and vector, a phenomenon essential for successful
      parasitism.

PMID- 22994898
TI  - Advanced care planning in health service users.
AB  - AIMS AND OBJECTIVES: To examine the use of advanced directives (ADs) in patients
      actively using health services in the USA. BACKGROUND: Since 1991, USA law (PSDA
      1991) has required hospitals, skilled nursing facilities (SNFs) and home health
      services to inquire, at admission, if patients have in place ADs, to provide
      patients with a written summary of their rights in regard to health-related
      decision-making and to provide education to staff and the community about ADs.
      DESIGN: Via chart review and observation, the AD status of patients residing in
      three SNFs during a six-week period was ascertained (n = 272). Those with ADs
      were further evaluated to examine the timing of the directive in regards to their
      health status. METHODS: Patients residing at SNFs were selected for study because
      SNF patients are admitted from the hospital; therefore, there are at least two
      opportunities - at hospital admission and at SNF admission - to inquire and
      educate about advance directives. RESULTS: Residents ranged in age from 35 to 100
      years and included patients admitted for short-term rehabilitaion after
      hospitalisation, as well as residents who were initially admitted after a
      hospitalisation but required long-term care. A full 90.44% (n = 246) entered
      skilled care without an AD, and 69.11% (n = 188) remained without an AD. The most
      likely reason for the development of an AD was lengthy decline in health status
      associated with multiple hospitalisations. CONCLUSIONS: Current law appears
      ineffective. A more appropriate approach is to encourage open dialogue about
      treatment options and quality of life. RELEVANCE TO CLINICAL PRACTICE: Given the
      rapidity with which populations are ageing in countries worldwide, ADs would
      appear to be a phenomenon that should be embraced. However, experience in the USA
      has called into question their usefulness.

PMID- 22994896
TI  - The influence of basic ventilation strategies and anesthetic techniques on
      cerebral oxygenation in the beach chair position: study protocol.
AB  - BACKGROUND: Beach chair positioning during general anesthesia is associated with
      a high incidence of cerebral desaturation; poor neurological outcome is a growing
      concern. There are no published data pertaining to changes in cerebral
      oxygenation seen with increases in the inspired oxygen fraction or end-tidal
      carbon dioxide in patients anesthetized in the beach chair position. Furthermore,
      the effect anesthetic agents have has not been thoroughly investigated in this
      context. We plan to test the hypothesis that changes in inspired oxygen fraction
      or end-tidal carbon dioxide correlate to a significant change in regional
      cerebral oxygenation in anesthetized patients in beach chair position. We will
      also compare the effects that inhaled and intravenous anesthetics have on this
      process. METHODS/DESIGN: This is a prospective within-group study of patients
      undergoing shoulder arthroscopy in the beach chair position which incorporates a
      randomized comparison between two anesthetics, approved by the Institutional
      Review Board of the University of Michigan, Ann Arbor. The primary outcome
      measure is the change in regional cerebral oxygenation due to sequential changes
      in oxygenation and ventilation. A sample size of 48 will have greater than 80%
      power to detect an absolute 4-5% difference in regional cerebral oxygenation
      caused by changes in ventilation strategy. The secondary outcome is the effect of
      anesthetic choice on cerebral desaturation in the beach chair position or
      response to changes in ventilation strategy. Fifty-four patients will be
      recruited, allowing for drop out, targeting 24 patients in each group randomized
      to an anesthetic. Regional cerebral oxygenation will be measured using the INVOS
      5100C monitor (Covidien, Boulder, CO). Following induction of anesthesia,
      intubation and positioning, inspired oxygen fraction and minute ventilation will
      be sequentially adjusted. At each set point, regional cerebral oxygenation will
      be recorded and venous blood gas analysis performed. The overall statistical
      analysis will use a repeated measures analysis of variance with Tukey's HSD
      procedure for post hoc contrasts. DISCUSSION: If simple maneuvers of ventilation
      or anesthetic technique can prevent cerebral hypoxia, patient outcome may be
      improved. This is the first study to investigate the effects of ventilation
      strategies on cerebral oxygenation in patients anesthetized in beach chair
      position. TRIAL REGISTRATION: NCT01535274.

PMID- 22994899
TI  - Quantitative visualization of biological data in Google Earth using R2G2, an R
      CRAN package.
AB  - We briefly introduce R2G2, an R CRAN package to visualize spatially explicit
      biological data within the Google Earth interface. Our package combines a
      collection of basic graph-editing features, including automated placement of
      dots, segments, polygons, images (including graphs produced with R), along with
      several complex three-dimensional (3D) representations such as phylogenies,
      histograms and pie charts. We briefly present some example data sets and show the
      immediate benefits in communication gained from using the Google Earth interface
      to visually explore biological results. The package is distributed with detailed
      help pages providing examples and annotated source scripts with the hope that
      users will have an easy time using and further developing this package. R2G2 is
      distributed on http://cran.r-project.org/web/packages.

PMID- 22994900
TI  - Primary cutaneous rhabdomyosarcoma: a clinicopathologic review of 11 cases.
AB  - BACKGROUND: Rhabdomyosarcoma is a malignant mesenchymal tumor with skeletal
      muscle differentiation. Primary cutaneous rhabdomyosarcoma is rare. We report a
      series of 11 cases of primary cutaneous rhabdomyosarcoma. METHODS: Cases
      diagnosed as rhabdomyosarcoma arising in the dermis/subcutis with no identified
      primary tumor elsewhere were retrospectively reviewed. Follow-up was obtained.
      RESULTS: The tumors occurred in five children and six adults. The adult subset
      consisted of pleomorphic, epithelioid and not otherwise specified (NOS) subtypes
      while the pediatric subset showed alveolar and embryonal subtypes. All cases
      showed immunohistochemical staining consistent with the diagnosis of
      rhabdomyosarcoma. Three adult cases showed immunoreactivity for cytokeratins (one
      pleomorphic, one epithelioid and one NOS. CONCLUSIONS: Primary cutaneous
      rhabdomyosarcoma shows a bimodal age distribution and male predominance,
      correlating with rhabdomyosarcoma in deep soft tissue. Follow-up, available on
      all patients, showed aggressive behavior in both children and adults. Primary
      cutaneous rhabdomyosarcoma should be considered in the differential diagnosis of
      tumors with abundant eosinophilic cytoplasm and those with "small round blue
      cell" morphology. Desmin, myogenin and MYOD1 are a trio of markers with high
      sensitivity and specificity for primary cutaneous rhabdomyosarcoma. Cytokeratin
      immunoreactivity in primary cutaneous rhabdomyosarcoma represents a potential
      diagnostic pitfall in the differential diagnosis with sarcomatoid carcinoma.

PMID- 22994901
TI  - Divergent modulation of clinical measures of volitional and reflexive motor
      behaviors following serotonergic medications in human incomplete spinal cord
      injury.
AB  - Incomplete spinal cord injury (SCI) can result in profound impairments in
      volitional strength and reflex excitability, which contribute to loss of
      function. Human and animal models suggest that disruption of endogenous
      monoaminergic input, particularly serotonin (5-HT), from supraspinal centers
      contributes to this impaired motor function following SCI. In the present study,
      we investigated the effects of 5-HT medications on motor function in individuals
      with chronic (>1 year) SCI. Clinical measures of strength, spasticity/spasms, and
      walking ability were assessed in 12 individuals with chronic incomplete SCI
      following acute administration of either 8 mg cyproheptadine, a 5-HT antagonist,
      or 10 mg escitalopram, a selective 5-HT reuptake inhibitor (SSRI), in a double
      blinded, randomized, crossover fashion. Results indicated that 5-HT medications
      modulated both volitional and reflexive behaviors with little change in walking
      performance; 5-HT antagonist medications depressed clinical measures of strength
      and spasticity/spasms, whereas SSRIs augmented both strength and
      spasticity/spasms. These changes are consistent with the dysregulation of 5-HT
      sensitive spinal neurons following SCI. This understanding may augment
      clinicians' awareness of the motor consequences of 5-HT medications.

PMID- 22994902
TI  - Low testosterone and hyperkinetic blood pressure responses in a cohort of South
      African men: the SABPA Study.
AB  - Hypertension (HT) and the metabolic syndrome are major problems in Africa. The
      role of sex hormones in the cardiovascular profile of black Africans in South
      Africa has not been studied. Our objective was to study the association between
      the sex hormones and ambulatory blood pressure and the heart rate (HR) in black
      and white South Africans. The 24-hour ambulatory blood pressure measurements were
      performed and the blood samples were taken between 07:00 and 09:00 hours. A total
      of 80 black and 98 white South African teachers between 25 and 65 years of age
      from similar socioeconomic backgrounds from the Sympathetic Activity and
      Ambulatory Blood Pressure in Africans (SABPA) study were included. As a result, a
      more vulnerable cardiovascular profile was observed in Africans compared with
      Caucasians. In the African group, low testosterone (T) explained 19%-36% of the
      variance in systolic blood pressure (SBP), diastolic blood pressure (DBP), and
      HR, whereas in the Caucasian group non-sex-hormone-binding globulin (non-SHBG)
      bound T explained 27% of the variance in HR. In the African males, inverse
      associations between blood pressure and T (SBP: P = .08; DBP: P = .02) and non
      SHBG-bound T (SBP: P < .001; DBP: P < .01) and HR (P < 0.01) were observed.
      Ambulatory HR predicted a prediabetic state in Africans. In conclusion, low T
      levels may predispose or result in impaired cardiovascular function in African
      men. The possibility exists that a prediabetic state, vagal-impaired HR, and
      hyperkinetic blood pressure responses may predispose or result in low T levels in
      African men.

PMID- 22994903
TI  - Field contamination of skeletonized human remains with exogenous DNA.
AB  - The Armed Forces DNA Identification Laboratory reports the mitochondrial DNA
      (mtDNA) sequences of over 800 skeletal samples a year for the Joint POW/MIA
      Accounting Command-Central Identification Laboratory. These sequences are
      generated from degraded skeletal remains that are presumed to belong to U.S.
      service members missing from past military conflicts. In the laboratory, it is
      possible to control for contamination of remains; however, in the field, it can
      be difficult to prevent modern DNA from being transferred to skeletal elements
      and being carried forward through the analysis process. Four such cases are
      described here along with the controls in place in the laboratory to eliminate
      the possibility of the exogenous DNA being reported as authentic. In each case,
      the controls implemented by the laboratories prevented the false reporting of
      contaminant exogenous DNA from remains that were either faunal or human, but
      lacked endogenous DNA.

PMID- 22994904
TI  - Long-term ethanol effects on acute stress responses: modulation by dynorphin.
AB  - The brain stress-response system is critically involved in the addiction process,
      stimulating drug consumption and the relapse to drug taking in abstinent addicts.
      At the same time, its functioning is affected by chronic drug exposure. Here, we
      have investigated the role of the endogenous opioid peptide dynorphin as a
      modulator of effects of long-term ethanol consumption on the brain stress
      response system. Using the two-bottle choice paradigm, we demonstrate an enhanced
      ethanol preference in male dynorphin knockout mice. Exposure to mild foot shock
      increased ethanol consumption in wild-type control littermates, but not in
      dynorphin-deficient animals. Blood adrenocorticotropic hormone levels determined
      5 minutes after the shock were not affected by the genotype. We also determined
      the neuronal reactivity after foot shock exposure using c-Fos immunoreactivity in
      limbic structures. This was strongly influenced by both genotype and chronic
      ethanol consumption. Long-term alcohol exposure elevated the foot shock-induced c
      Fos expression in the basolateral amygdala in wild-type animals, but had the
      opposite effect in dynorphin-deficient mice. An altered c-Fos reactivity was also
      found in the periventricular nucleus, the thalamus and the hippocampus of
      dynorphin knockouts. Together these data suggest that dynorphin plays an
      important role in the modulation of the brain stress-response systems after
      chronic ethanol exposure. 

PMID- 22994905
TI  - Analysis of longitudinal clinical trials with missing data using multiple
      imputation in conjunction with robust regression.
AB  - In a typical randomized clinical trial, a continuous variable of interest (e.g.,
      bone density) is measured at baseline and fixed postbaseline time points. The
      resulting longitudinal data, often incomplete due to dropouts and other reasons,
      are commonly analyzed using parametric likelihood-based methods that assume
      multivariate normality of the response vector. If the normality assumption is
      deemed untenable, then semiparametric methods such as (weighted) generalized
      estimating equations are considered. We propose an alternate approach in which
      the missing data problem is tackled using multiple imputation, and each imputed
      dataset is analyzed using robust regression (M-estimation; Huber, 1973, Annals of
      Statistics 1, 799-821.) to protect against potential non-normality/outliers in
      the original or imputed dataset. The robust analysis results from each imputed
      dataset are combined for overall estimation and inference using either the simple
      Rubin (1987, Multiple Imputation for Nonresponse in Surveys, New York: Wiley)
      method, or the more complex but potentially more accurate Robins and Wang (2000,
      Biometrika 87, 113-124.) method. We use simulations to show that our proposed
      approach performs at least as well as the standard methods under normality, but
      is notably better under both elliptically symmetric and asymmetric non-normal
      distributions. A clinical trial example is used for illustration.

PMID- 22994906
TI  - Outcomes of living and deceased donor liver transplant recipients with
      hepatocellular carcinoma: results of the A2ALL cohort.
AB  - Hepatocellular carcinoma (HCC) represents an increasing fraction of liver
      transplant indications; the role of living donor liver transplant (LDLT) remains
      unclear. In the Adult-to-Adult Living Donor Liver Transplantation Cohort Study,
      patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which
      at least one potential living donor had been evaluated were compared for
      recurrence and posttransplant mortality rates. Mortality from date of evaluation
      of each recipient's first potential living donor was also analyzed. Unadjusted 5
      year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p
      = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained
      significantly different between LDLT and DDLT recipients (hazard ratio (HR) =
      2.35; p = 0.04) for the overall cohort but not for recipients transplanted
      following the introduction of MELD prioritization. Five-year posttransplant
      survival was similar in LDLT and DDLT recipients from time of transplant (HR =
      1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We
      conclude that the higher recurrence observed after LDLT is likely due to
      differences in tumor characteristics, pretransplant HCC management and waiting
      time.

PMID- 22994907
TI  - Suboccipital decompression enhances heart rate variability indices of cardiac
      control in healthy subjects.
AB  - OBJECTIVES: Osteopathic manipulative treatment (OMT) focused on the upper
      cervical spine is theorized to affect the function of the vagus nerve and thereby
      influence the parasympathetic branch of the autonomic nervous system. This study
      was designed to determine the acute effect of upper cervical spine manipulation
      on cardiac autonomic control as measured by heart rate variability. DESIGN:
      Nineteen healthy, young adult subjects underwent three different experimental
      interventions administered in random order: cervical OMT, sham manipulation, and
      time control. Six minutes of electrocardiographic data were collected before and
      after each intervention, and heart rate variability was assessed by both time
      domain and frequency-domain measures. RESULTS: No differences in resting heart
      rate or any measure of heart rate variability were observed between the baseline
      periods prior to each intervention. The OMT protocol resulted in an increase in
      the standard deviation of the normal-to-normal intervals (0.12+/-0.082 seconds,
      p<0.01), an increase in the high frequency spectral power (p=0.03), and a
      decrease in the low/high frequency spectral ratio (p=0.01) relative to the sham
      and time control conditions. No significant differences between sham and time
      control were observed (p>0.11 for all variables). CONCLUSIONS: These data support
      the hypothesis that upper cervical spine manipulation can acutely affect measures
      of heart rate variability in healthy individuals.

PMID- 22994908
TI  - Sunscreen use and melanocytic nevi in children: a systematic review.
AB  - We conducted a systematic review of the association between melanocytic nevi (MN)
      in childhood and sunscreen use. A bibliographic search was conducted between
      November 2008 and January 2009 using the following key words on MEDLINE and
      EMBASE: child*, in combination with naevi, nevi, naevus, nevus and sunscreen, sun
      protection. We also used Medical Subject Headings [sunscreening agents], or
      [radiation protection] with [nevus, pigmented]. A first screening was done on
      title and abstract reading. Randomized trials and cohort and cross-sectional
      studies analyzing the relationship between the use of sunscreen and MN in
      children were selected. Three reviewers abstracted data from each article. The
      three sets of results were compared for concordance and rereviewed if necessary.
      Fifteen articles were included (20,743 children). The studies were not consistent
      in terms of the ages of the children, MN count methods, or sunscreen use
      assessment. Owing to this heterogeneity, we were unable to pool the studies and
      conduct a meta-analysis. Twelve studies did not report that the use of sunscreen
      had a protective effect against MN development. Three studies reported a lower MN
      count when sunscreen was applied. This systematic review underlines the
      methodologic differences between studies. Eight of 15 studies reported a positive
      association between sunscreen application and MN count. Differences in MN counts,
      overexposure to sun, and inadequate sunscreen application on fair-skinned
      children could explain the disparity in the results. There is still no evidence
      of a protective effect of sunscreen against MN development in children.

PMID- 22994909
TI  - Morphologies of the atria and pulmonary veins in relation to lone atrial
      fibrillation progression: a dual-source computed tomography scan study.
AB  - Atrial Remodeling and Lone Atrial Fibrillation. BACKGROUND: We sought to
      investigate the role of anatomic remodeling of the atria and pulmonary veins
      (PVs) in the progression of lone atrial fibrillation (AF) using dual-source
      computed tomography (DSCT). METHODS AND RESULTS: From 1,308 consecutive patients
      referred for an index ablation procedure for AF, we prospectively enrolled 29
      consecutive patients with recently developed (<3 months) lone persistent AF
      (PsAF) and 23 consecutive patients with short-lasting (6-12 months) lone PsAF,
      all of whom had a history of paroxysmal AF (PAF). The control group consisted of
      33 patients with lone PAF. On DSCT, the recently developed PsAF group showed more
      extensive atrial anatomic remodeling than the PAF group as shown by ~40% higher
      spot biatrial volume, even though the mean duration of continuous AF was only 6
      weeks. In contrast, the DSCT variables in the recently developed PsAF group and
      the short-lasting PsAF group were comparable, despite the fact that the mean
      duration of continuous AF in the latter group was 8 months. Series of cross
      sectional areas of the ostial 1.5 cm of PV trunks were comparable in the PAF and
      PsAF groups in all but 3 ostial planes. A higher spot left atrial volume was the
      only independent factor associated with the progression of lone PAF to PsAF (OR:
      1.06, 95% CI: 1.03-1.09, P<0.0001) on logistic regression. CONCLUSIONS: Prominent
      anatomic remodeling of the atria, rather than the PVs, underlies the mechanism of
      recent progression of lone paroxysmal AF to the persistent variety.

PMID- 22994910
TI  - Enhanced maternal and child health nurse care for women experiencing intimate
      partner/family violence: protocol for MOVE, a cluster randomised trial of
      screening and referral in primary health care.
AB  - BACKGROUND: Intimate partner violence (IPV) can result in significant harm to
      women and families and is especially prevalent when women are pregnant or recent
      mothers. Maternal and child health nurses (MCHN) in Victoria, Australia are
      community-based nurse/midwives who see over 95% of all mothers with newborns.
      MCHN are in an ideal position to identify and support women experiencing IPV, or
      refer them to specialist family violence services. Evidence for IPV screening in
      primary health care is inconclusive to date. The Victorian government recently
      required nurses to screen all mothers when babies are four weeks old, offering an
      opportunity to examine the effectiveness of MCHN IPV screening practices. This
      protocol describes the development and design of MOVE, a study to examine IPV
      screening effectiveness and the sustainability of screening practice.
      METHODS/DESIGN: MOVE is a cluster randomised trial of a good practice model of
      MCHN IPV screening involving eight maternal and child health nurse teams in
      Melbourne, Victoria. Normalisation Process Theory (NPT) was incorporated into the
      design, implementation and evaluation of the MOVE trial to enhance and evaluate
      sustainability. Using NPT, the development stage combined participatory action
      research with intervention nurse teams and a systematic review of nurse IPV
      studies to develop an intervention model incorporating consensus guidelines,
      clinical pathway and strategies for individual nurses, their teams and family
      violence services. Following twelve months' implementation, primary outcomes
      assessed include IPV inquiry, IPV disclosure by women and referral using data
      from MCHN routine data collection and a survey to all women giving birth in the
      previous eight months. IPV will be measured using the Composite Abuse Scale.
      Process and impact evaluation data (online surveys and key stakeholders
      interviews) will highlight NPT concepts to enhance sustainability of IPV
      identification and referral. Data will be collected again in two years.
      DISCUSSION: MOVE will be the first randomised trial to determine IPV screening
      effectiveness in a community based nurse setting and the first to examine
      sustainability of an IPV screening intervention. It will further inform the
      debate about the effectiveness of IPV screening and describe IPV prevalence in a
      community based post-partum and early infant population. TRIAL REGISTRATION:
      ACTRN12609000424202.

PMID- 22994911
TI  - Genomic dissection of small RNAs in wild rice (Oryza rufipogon): lessons for rice
      domestication.
AB  - The lack of a MIRNA set and genome sequence of wild rice (Oryza rufipogon) has
      prevented us from determining the role of MIRNA genes in rice domestication. In
      this study, a genome, three small RNA populations and a degradome of O. rufipogon
      were sequenced by Illumina platform and the expression levels of microRNAs
      (miRNAs) were investigated by miRNA chips. A de novo O. rufipogon genome was
      assembled using c. 55* coverage of raw sequencing data and a total of 387 MIRNAs
      were identified in the O. rufipogon genome based on c. 5.2 million unique small
      RNA reads from three different tissues of O. rufipogon. Of these, O. rufipogon
      MIRNAs, 259 were not found in the cultivated rice, suggesting a loss of these
      MIRNAs in the cultivated rice. We also found that 48 MIRNAs were novel in the
      cultivated rice, suggesting that they were potential targets of domestication
      selection. Some miRNAs showed significant expression differences between wild and
      cultivated rice, suggesting that expression of miRNA could also be a target of
      domestication, as demonstrated for the miR164 family. Our results illustrated
      that MIRNA genes, like protein-coding genes, might have been significantly shaped
      during rice domestication and could be one of the driving forces that contributed
      to rice domestication.

PMID- 22994913
TI  - One-step electrophoretic deposition of reduced graphene oxide and Ni(OH)2
      composite films for controlled syntheses supercapacitor electrodes.
AB  - A facile, rapid, scalable, and environmentally friendly electrophoretic
      deposition (EPD) approach has been developed for the fabrication of reduced
      graphene oxide (RGO) and Ni(OH)(2) syntheses based on EPD of graphene oxide (GO)
      and Ni(NO(3))(2) colloidal suspension. Nickel ion decoration made GO positively
      charged and further made cathodic EPD feasible. Direct assembly by one-step EPD
      facilitated transformation from GO to RGO and resulted in multilayer or flower
      like RGO/Ni(OH)(2) hybrid films on different substrates. X-ray diffraction
      analysis suggested that the crystal structures of Ni(OH)(2) depended on the
      colloidal suspension and the substrate. Further transmission electron microscopy
      characterization indicated that Ni(OH)(2) nanoclusters composed of 5-10 nm
      nanoparticles in grain size were homogeneously dispersed and anchored on the RGO.
      The resulting 100% binder-free RGO/Ni(OH)(2) electrodes exhibited excellent
      pseudocapacitive behavior with high specific capacitance of 1404 F g(-1) at 2 A
      g(-1), high rate capability, and good electrochemical cyclic stability. These
      results paved the way for EPD to produce RGO-based nanocomposite films for high
      performance energy storage devices.

PMID- 22994914
TI  - Prevalence of scientific misconduct among a group of researchers in Nigeria.
AB  - BACKGROUND: There is a dearth of information on the prevalence of scientific
      misconduct from Nigeria. OBJECTIVES: This study aimed at determining the
      prevalence of scientific misconduct in a group of researchers in Nigeria. Factors
      associated with the prevalence were ascertained. METHOD: A descriptive study of
      researchers who attended a scientific conference in 2010 was conducted using the
      adapted Scientific Misconduct Questionnaire-Revised (SMQ-R). RESULTS: Ninety-one
      researchers (68.9%) admitted having committed at least one of the eight listed
      forms of scientific misconduct. Disagreement about authorship was the most common
      form of misconduct committed (36.4%) while plagiarism was the least (9.2%). About
      42% of researchers had committed falsification of data or plagiarism. Analysis of
      specific acts of misconduct showed that committing plagiarism was inversely
      associated with years in research (Fisher exact p-value = 0.02); falsifying data
      was related to perceived low effectiveness of the institution's rules and
      procedures for reducing scientific misconduct (X(2) = 6.44, p-value = 0.01); and
      succumbing to pressure from study sponsor to engage in unethical practice was
      related to sex of researcher (Fisher exact p-value = 0.02). CONCLUSIONS: The
      emergent data from this study is a cause for serious concern and calls for prompt
      intervention. The best response to reducing scientific misconduct will proceed
      from measures that contain both elements of prevention and enforcement. Training
      on research ethics has to be integrated into the curriculum of undergraduate and
      postgraduate students while provision should be made for in-service training of
      researchers. Penalties against acts of scientific misconduct should be enforced
      at institutional and national levels.

PMID- 22994912
TI  - Effects of fish oil supplementation on inflammatory markers in chronic heart
      failure: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Effects of fish oil on systematic inflammation in chronic heart
      failure remain unclear. In this meta-analysis, we aimed to evaluate the influence
      of fish oil supplementation on circulating levels of inflammatory markers in
      patients with chronic heart failure. METHODS: Human randomized controlled trials,
      which compared the effects of fish oil supplementation with placebo in patients
      with chronic heart failure, were identified by systematic search of Medline,
      Embase, Cochrane's library and references cited in related reviews and studies up
      to November 2011. Outcome measures comprised the changes of circulating
      inflammatory markers. Meta-analysis was performed with the fixed-effect model or
      random-effect model according to the heterogeneity. RESULTS: A total of seven
      trials with eight study arms were included. The pooled results indicated
      circulating levels of tumor necrosis factor alpha (SMD = -0.62, 95% CI -1.08 to 
      0.16, p = 0.009), interleukin 1 (SMD = -1.24, 95% CI -1.56 to -0.91, p < 0.001)
      and interleukin 6 (SMD = -0.81, 95% CI -1.48 to -0.14, p = 0.02) were
      significantly decreased after fish oil supplementation; however, high sensitivity
      C reactive protein, soluble intracellular adhesion molecular 1 and vascular cell
      adhesion molecular 1 were not significantly affected. Meta-regression and
      subgroup analysis results suggested the difference in dose of fish oil and follow
      up duration might influence the effects of fish oil on tumor necrosis factor
      alpha and interleukin 6. Greater reduction of these two markers might be achieved
      in patients taking fish oil of a higher dose (over 1000 mg/day) or for a longer
      duration (over 4 months). CONCLUSIONS: Limited evidence suggests anti
      inflammation may be a potential mechanism underlying the beneficial effects of
      fish oil for chronic heart failure. Further large-scale and adequately powered
      clinical trials are needed to confirm these effects.

PMID- 22994915
TI  - Non-O157:H7 Shiga toxin-producing Escherichia coli in bovine rectums and surface
      water streams on a beef cattle farm in Argentina.
AB  - The purposes of this study were to detect non-O157 Shiga toxin-producing
      Escherichia coli (STEC) in bovine rectums and water in a beef cattle farm in
      Argentina, and to determine the pathogenic potential of the circulating strains.
      During the study, 292 rectal swabs from healthy animals and 79 environmental
      water samples were collected. The rectal swabs and one loop of the Moore swabs,
      enriched in Escherichia coli broth for 24 h at 37 degrees C, were streaked on
      MacConkey agar plates and incubated overnight at 37 degrees C. The isolates were
      characterized by biochemical tests and serotyped. Nonmotile STEC strains were
      typed for their H-specific (fliC) antigens by polymerase chain reaction (PCR).
      Isolates were characterized by detection of stx1, stx2, and their variants, eae,
      ehxA, and saa genes. Macrorestriction fragment analysis by pulsed-field gel
      electrophoresis (PFGE) was performed using the PulseNet standardized protocol.
      From 371 samples analyzed, 36.6% of rectal swabs and 34.2% of water samples were
      non-O157 STEC-positive by PCR, and 110 strains from rectal swabs, but only three
      from water, were isolated. The strains were grouped into 24 different serotypes,
      from which, O103:[H2] (n = 12), O136:H12 (n = 8), O178:H19 (n = 8), and O103:NM
      (n = 5) were most prevalent, representing 29.2% of the isolates. Predominant
      genotypes were stx1/eae/ehxA (16.8%) and stx2/saa/ehxA (15.9%). PFGE analysis
      revealed 56 different patterns, with 65 strains grouped in 19 clusters of 100%
      similarity. Two STEC O124:H19 strains isolated from rectal swabs and water with a
      5-month interval harbored the stx1/stx2/saa/ehxA genotype, and showed an
      indistinguishable PFGE profile. By comparison, some XbaI-PFGE patterns identified
      in the present study were identical to the profiles of strains isolated from
      human, food, and animal sources included in the Argentine PulseNet database. By
      PCR, similar non-O157 detection rates were found in rectal swabs and water.
      However, the methodology for water samples needs to be improved, since only three
      strains from the total number of positive samples were recovered.

PMID- 22994916
TI  - Working in partnership with parents: the experience and challenge of practice
      innovation in child and family health nursing.
AB  - AIMS AND OBJECTIVE: This study investigated what Family Partnership Model
      practice means in the day-to-day practice of child and family health nurses
      working with parents. BACKGROUND: The Family Partnership Model has been widely
      implemented in child and family health services in Australia and New Zealand,
      with limited understanding of the implications for nursing practice. DESIGN: A
      qualitative interpretive study design was used. METHOD: Semi-structured
      interviews were conducted with 22 nurse participants, who had completed the
      Family Partnership Model training programme. Subsequent focus groups enabled
      these participants to validate the themes identified in the initial analysis and
      to confirm that the nurses concurred with the issues raised. Thematic content
      analysis produced rich descriptions and explanation of nurses' experiences and
      perspectives. results: Four themes emerged from the analysis: experience of
      changing practices, exploring with parents, challenging unhelpful constructions
      and a commitment to examining practice. CONCLUSION: Overall, the participants
      embraced the use of the Family Partnership Model, providing examples of change
      and increasing confidence in their approach to working with parents. RELEVANCE TO
      CLINICAL PRACTICE: This study demonstrates that the effective utilisation of the
      Family Partnership Model in nursing practice is a more complex and dynamic
      process than simply embracing the model. There are significant challenges to be
      negotiated when implementing new ways of working with parents, particularly
      questioning existing dominant forms of practice for nurses, managers and wider
      health organisations, and their clients. This paper also raises issues about
      sustaining practice innovation, which extends beyond the best intent of
      individual nurses, requiring receptive organisational conditions and leadership.

PMID- 22994917
TI  - Biogenic phosphorus compounds in sediment and suspended particles in a shallow
      eutrophic lake: a 31P-nuclear magnetic resonance (31P NMR) study.
AB  - Differences in biogenic phosphorus (P) compounds between sediment and suspended
      particles in aquatic environments are important for understanding the mechanisms
      of internal P loading, but these differences are still unknown. We used solution
      state (31)P-nuclear magnetic resonance spectroscopy ((31)P NMR) with NaOH
      ethylenediaminetetraacetic extraction to detect the multiple P compounds in
      suspended particles and sediment in the eutrophic Lake Kasumigaura, including
      orthophosphate monoesters, orthophosphate diesters, pyrophosphate, and
      polyphosphate. We tested the hypothesis that there is a significant difference
      between these groups in suspended particles and sediment. Biogenic P other than
      orthophosphate was found in significantly higher proportions in suspended
      particles (74.3% of total P) than in sediment (25.6%). Orthophosphate monoesters
      were comparatively more abundant in suspended particles, as indicated by the
      ratio of orthophosphate diesters to monoesters (average, 0.31 for suspended
      particles; 1.05 for sediment). The compounds identified as orthophosphate
      monoesters by (31)P NMR spectroscopy originated mainly from phospholipids (alpha
      glycerophosphate and beta-glycerophosphate) and ribonucleic acid (RNA-P), whereas
      the orthophosphate diesters included mostly DNA (DNA-P). These results suggest
      that the dynamics of orthophosphate diesters, the production of DNA-P, or the
      degradation of phospholipids, play an important role in P cycling in Lake
      Kasumigaura.

PMID- 22994918
TI  - Cross-sectional and longitudinal associations of functional and health status
      with institutional care use: results from the Survey of Health and Living Status
      of the Elderly in Taiwan.
AB  - AIM: This study evaluated the cross-sectional and longitudinal associations of
      functional and health status with institutional care, and examined determinants
      of institutional care use over time. METHODS: Data of this study were obtained
      from the Survey of Health and Living Status of the Elderly in Taiwan (SHLSET),
      which was launched in 1989 and involved a nationally representative sample of
      nearly-old and old Taiwanese. The baseline data in this present study were
      collected in 1999, and followed in 2003 and 2007. RESULTS: Participants with
      institutional care use had a higher activities of daily living (ADL) score, more
      self-reported diseases and poorer self-reported health status than participants
      without institutional care use (all P<0.05). Cross-sectional analysis showed that
      a higher ADL score, having heart diseases and having a stroke were positively
      associated with institutional care use (P<0.05); whereas the number of self
      reported diseases and poor self-reported health status were not associated with
      institutional care use. Longitudinal analysis showed that increased ADL scores
      and the number of self-reported diseases over 4- and 8 years were associated with
      an increased likelihood of subsequent institutional care use (all P<0.05).
      Worsening health status over 4 years was associated with an increased likelihood
      of subsequent institutional care use, but this association did not exist over 8
      years. CONCLUSIONS: Only ADL and ADL deterioration over time are cross
      sectionally and longitudinally associated with increased institutional care use.
      Declining functional status is a major determinant of institutional care use for
      Taiwanese aged over 53 years.

PMID- 22994919
TI  - Bringing the laboratory and clinic to the community: mobile technologies for
      health promotion and disease prevention.
AB  - Health-related information collected in psychological laboratories may not be
      representative of people's everyday health. For at least 70 years, there has been
      a call for methods that sample experiences from everyday environments and
      circumstances. New technologies, including cell phones, sensors, and monitors,
      now make it possible to collect information outside of the laboratory in
      environments representative of everyday life. We review the role of mobile
      technologies in the assessment of health-related behaviors, physiological
      responses, and self-reports. Ecological momentary assessment offers a wide range
      of new opportunities for ambulatory assessment and evaluation. The value of
      mobile technologies for interventions to improve health is less well established.
      Among 21 randomized clinical trials evaluating interventions that used mobile
      technologies, more than half failed to document significant improvements on
      health outcomes or health risk factors. Theoretical and practical issues for
      future research are discussed.

PMID- 22994920
TI  - Sexual prejudice.
AB  - Despite shifts toward greater acceptance in U.S. public opinion and policy,
      lesbian, gay, and bisexual people remain widely stigmatized. This article reviews
      empirical research on sexual prejudice, that is, heterosexuals' internalization
      of cultural stigma, manifested in the form of negative attitudes toward sexual
      minorities and same-sex desires and behaviors. After briefly reviewing
      measurement issues, we discuss linkages between sexual prejudice and religion,
      gender, sexuality, and related variables, and consider how the cultural
      institutions encompassing these domains create a social context within which
      individual expressions of prejudice can meet important psychological needs. These
      include needs for securing social acceptance, affirming values that are central
      to one's self-concept, and avoiding anxiety and other negative emotions
      associated with threats to self-esteem. We conclude by discussing factors that
      may motivate heterosexuals to reduce their own sexual prejudice, including
      intergroup contact, as well as avenues for future empirical inquiry.

PMID- 22994921
TI  - A cultural neuroscience approach to the biosocial nature of the human brain.
AB  - Cultural neuroscience (CN) is an interdisciplinary field that investigates the
      relationship between culture (e.g., value and belief systems and practices shared
      by groups) and human brain functions. In this review we describe the origin,
      aims, and methods of CN as well as its conceptual framework and major findings.
      We also clarify several misunderstandings of CN research. Finally, we discuss the
      implications of CN findings for understanding human brain function in
      sociocultural contexts and novel questions that future CN research should
      address. By doing so, we hope to provide a clear picture of the CN approach to
      the human brain and culture and to elucidate the intrinsically biosocial nature
      of the functional organization of the human brain.

PMID- 22994922
TI  - Shifting gears: seeking new approaches for mind/brain mechanisms.
AB  - Using an autobiographical approach, I review several animal and human split-brain
      studies that have led me to change my long-term view on how best to understand
      mind/brain interactions. Overall, the view is consistent with the idea that
      complex neural systems, like other complex information processing systems, are
      highly modular. At the same time, how the modules come to interact and produce
      unitary goals is unknown. Here, I review the importance of self-cueing in that
      process of producing unitary goals from disparate functions. The role of self
      cueing is demonstrably evident in the human neurologic patient and especially in
      patients with hemispheric disconnection. When viewed in the context of
      modularity, it may provide insights into how a highly parallel and distributed
      brain locally coordinates its activities to produce an apparent unitary output.
      Capturing and understanding how this is achieved will require shifting gears away
      from standard linear models and adopting a more dynamical systems view of brain
      function.

PMID- 22994923
TI  - Mycophenolate mofetil maintenance therapy in renal transplant patients: long-term
      results of the TranCept STAY study.
AB  - BACKGROUND: This prospective observational study documented long-term renal
      function in transplant recipients receiving mycophenolate mofetil (MMF). METHODS:
      Kidney allograft recipients>6 months post-transplantation, with a glomerular
      filtration rate (GFR)>20 mL/min, receiving MMF from time of transplantation were
      enrolled and followed for four yr. Subgroups were identified based on time
      between transplantation and enrollment: Y<1 (6 months-1 yr); Y1-2 (>1-2 yr); Y2-5
      (>2-5 yr) and Y>5 (>5 yr). RESULTS: A total of 2040 patients were analyzed; 780,
      410, 541 and 309 in subgroups Y<1, Y1-2, Y2-5 and Y>5. For all patients combined
      GFR decreased during the observational period by approximately 1 mL/min/yr
      (median GFR (mL/min) was 50.8, 50.5, 48.7, and 47.6 at one, two, three, and four
      yr). Survival estimates for decline in renal function (>20% GFR decline at one
      time point) were 78%, 66%, 57%, and 51% at one, two, three and four yr, with no
      significant differences between subgroups (p>0.05). In adult patients, higher
      doses of MMF (>=1 g/d) were associated with better GFR outcomes (median GFR
      (mL/min) 48.1 vs. 39.9 at four yr post-enrollment; p=0.0037). When comparing the
      effects of MMF combined with calcineurin inhibitors (CNIs), GFR was increased
      with lower doses of tacrolimus or cyclosporin. There were no major tolerability
      or acute rejection problems and graft survival was similar in all subgroups
      (graft survival estimates for all patients combined were 99%, 95%, 92%, and 90%
      at one, two, three, and four yr). CONCLUSIONS: Long-term MMF immunosuppression
      preserves renal function and higher MMF doses combined with lower CNI doses may
      provide better patient outcomes.

PMID- 22994924
TI  - Characterization of in vitro cultured bone marrow and adipose tissue-derived
      mesenchymal stem cells and their ability to express neurotrophic factors.
AB  - MSCs (mesenchymal stem cells) have attracted attention as a promising tool for
      regenerative medicine and transplantation therapy. MSCs exert neuroprotective
      effects by secreting a number of factors in vitro and in vivo. Similar
      characteristics are found in ADSCs (adipose-derived stem cells) and BMSCs (bone
      marrow stromal cells). Multipotent capability, easy accessibility and rapid
      proliferation of ADSCs have been established. Our main objective was to compare
      cell viability, growth rate, expression of neurotrophic factors and nestin genes
      in ADSCs and BMSCs. Cell doubling time and proliferation rate indicate that ADSCs
      has a higher proliferation rate than BMSCs. ADSCs and BMSCs express a similar
      pattern of CD71 and CD90 markers. Nestin immunostaining showed that ADSCs and
      BMSCs are immunopositive. The expression of neurotrophic factors genes in ADSCs
      proved similar to that of BMSCs genes. Thus adipose tissue stem cells with a high
      proliferation rate can express nestin and neurotrophic factor genes. Therefore
      ADSCs may be useful in future cell replacement therapies and help improve
      neurodegenerative diseases.

PMID- 22994925
TI  - A pH-sensitive, colorful, lanthanide-chelating paramagnetic NMR probe.
AB  - Paramagnetic lanthanides ions are broadly used in NMR spectroscopy. The effects
      of unpaired electrons on NMR spectral parameters provide a powerful tool for the
      characterization of macromolecular structures and dynamics. Here, a new
      lanthanide-chelating NMR probe, Caged Lanthanide NMR Probe-7 (CLaNP-7), is
      presented. It can be attached to protein surfaces via two disulfide bridges,
      yielding a probe that is rigid relative to the protein backbone. CLaNP-7 extends
      the application range of available probes. It has a yellow color, which is
      helpful for sample preparation. Its effects are comparable to those of CLaNP-5,
      but its charge is two units lower (+1) than that of CLaNP-5 (+3), reducing the
      change in surface potential after probe attachment. It also has a different
      magnetic susceptibility tensor, so by using both tags, two sets of structural
      restraints can be obtained per engineered cysteine pair. Moreover, it was found
      that the orientation of the magnetic susceptibility tensor is pH dependent (pK(a)
      ~ 7) when a histidine residue is located in the neighborhood of the probe
      attachment site. The results show that the His imidazole group interacts with the
      CLaNP-7 tag. It is proposed that the histidine residue forms a hydrogen bond to a
      water/hydroxyl molecule that occupies the ninth coordination position on the
      lanthanide, thus breaking the two-fold symmetry of the CLaNP tag in a pH
      dependent way.

PMID- 22994926
TI  - De novo assembly of the transcriptome of an invasive snail and its multiple
      ecological applications.
AB  - Studying how invasive species respond to environmental stress at the molecular
      level can help us assess their impact and predict their range expansion.
      Development of markers of genetic polymorphism can help us reconstruct their
      invasive route. However, to conduct such studies requires the presence of
      substantial amount of genomic resources. This study aimed to generate and
      characterize genomic resources using high throughput transcriptome sequencing for
      Pomacea canaliculata, a nonmodel gastropod indigenous to Argentina that has
      invaded Asia, Hawaii and southern United States. De novo assembly of the
      transcriptome resulted in 128,436 unigenes with an average length of 419 bp
      (range: 150-8556 bp). Many of the unigenes (2439) contained transposable
      elements, showing the existence of a source of genetic variability in response to
      stressful conditions. A total of 3196 microsatellites were detected in the
      transcriptome; among 20 of the randomly tested microsatellites, 10 were validated
      to exhibit polymorphism. A total of 15,412 single-nucleotide polymorphisms (SNPs)
      were detected in the ORFs. LC-MS/MS analysis of the proteome of juveniles
      revealed 878 proteins, of which many are stress related. This study has
      demonstrated the great potential of high throughput DNA sequencing for rapid
      development of genomic resources for a nonmodel organism. Such resources can
      facilitate various molecular ecological studies, such as stress physiology and
      range expansion.

PMID- 22994927
TI  - Neuropsychological outcome of mTBI: a principal component analysis approach.
AB  - The multitude of variables associated with a battery of outcome measures presents
      a risk for spurious findings in clinical trials and observational studies of mild
      traumatic brain injury (mTBI). We have used principal components analysis (PCA)
      to facilitate data reduction by identifying components which represent subsets of
      neuropsychological measures that are selectively correlated with each other. By
      merging data from two concurrent mTBI studies using the same outcome measures, we
      obtained a cohort of 102 mTBI patients and 85 orthopedic injury (OI) comparison
      patients whom we recruited from 24 hours to 96 hours post-injury and evaluated at
      one week, 1 month, and 3 months post-injury. Cognitive domains included episodic
      memory, evaluated by both verbal and visual memory tasks, cognitive processing
      speed tests, and executive function. Post-concussion and stress-related symptoms
      were measured by rating scales. PCA identified four components, including
      cognitive processing speed, verbal memory, visual memory, and a symptom composite
      representing post-concussion and stress symptoms. mTBI patients older than the
      mean age of 18 years had slower cognitive processing than the OI patients, but
      there was no group difference in cognitive processing speed in younger patients.
      The symptom component score differed significantly as mTBI patients had more
      severe symptoms than the OI group at each occasion. Our results encourage
      replication with other cohorts using either the same outcome measures or at least
      similar domains. PCA is an approach to data reduction that could mitigate
      spurious findings and increase efficiency in mTBI research.

PMID- 22994928
TI  - Alternate light sources in the detection of bone after an accelerated fire: a
      pilot study.
AB  - This study examines the ability of alternate light sources to detect bone that
      has been exposed to fire when identification of bone remains is difficult to
      ascertain. It is intended as a tool for fire investigators to quickly determine
      whether an area should be considered a forensic scene. After being subjected to a
      test burn, pig bones were viewed and photographed with the use of a laser, and
      later compared with a UV light source. A secondary study observing stages of a
      human cremation was conducted to assess how various levels of burnt flesh affect
      the ability of bone to fluoresce utilizing a laser. Both studies demonstrated
      success in detecting bone while fluorescing with a molten lava type of appearance
      that has the potential to distinguish bone from its surrounding environment.
      Limitations and recommendations are discussed by the author including the need
      for future studies to expand on this research.

PMID- 22994929
TI  - Familial granular cell tumors: a case report and review of the literature.
AB  - Granular cell tumors are uncommon neoplasms postulated to derive from Schwann
      cells. They are histologically unique and exhibit S-100 positivity. Pediatric
      occurrences are uncommon, and familial cases are rare. A limited number of
      familial granular cell tumors have been reported. We describe two siblings with
      granular cell tumors and review the relevant literature.

PMID- 22994930
TI  - Mycosis fungoides involving an acrochordon: a case report.
AB  - We present the case of a 77-year-old male undergoing treatment for mycosis
      fungoides (MF) who presented for removal of an acrochordon on his mid back.
      Histopathologic examination of the acrochordon revealed a dense, band-like
      lymphocytic inflammatory infiltrate in the dermis with epidermotropism of single
      lymphocytes and small nests of lymphocytes into the lower epidermis.
      Immunohistochemical staining characterized the dermal and epidermal lymphocytic
      population as CD3-positive T lymphocytes with a predominance of CD4-positive over
      CD8-positive lymphocytes. These findings were consistent with the patient's known
      MF and molecular identification of a clonal T-cell receptor gene rearrangement
      further supported the diagnosis. Our unusual case reports MF involving an
      acrochordon and provides evidence to support the importance of submitting
      acrochordons for histopathologic examination.

PMID- 22994931
TI  - Systemic complications of trinitrotoluene (TNT) in exposed workers.
AB  - INTRODUCTION: 2,4,6-trinitrotoluene (TNT) has been widely used as an explosive.
      TNT can induce some well-recognized toxic impacts comprising toxic hepatitis,
      aplastic anemia and cataract. The aim of study was evaluation of TNT exposed
      workers for systemic complication. METHODS: In a cross-sectional study, we
      carried out Liver Function Test (LFT), complete blood count (CBC) and slit lamp
      biomicroscopy to compare the prevalence and severity of these 3 complications
      between 47 male TNT exposed workers (with at least one year continuous experience
      of TNT exposure) and 43 unexposed male hospital worker who hadn't had any
      previous contacts with TNT. We also performed Pulmonary Function Test (PFT) to
      assess the probable obstructive/restrictive abnormalities, caused by TNT.
      RESULTS: Mean alkaline phosphatase (ALP) level of TNT exposed group was
      significantly higher than the unexposed group (p = 0.023) Forced Expiratory
      Volume in one second to Forced Vital Capacity (FEV1/FVC) ratios of both groups
      were in the range of restrictive pattern (82.03% and 81.42% for the exposed and
      unexposed group, respectively) with no meaningful difference. We didn't find out
      any specific TNT induced cataract and general cortical cataract (CC) and nuclear
      sclerotic cataract (NSC) prevalence was not significantly different. DISCUSSION:
      we haven't found TNT as a chemical, causing toxic hepatitis or aplastic anemia;
      neither did we find it as a compound, responsible for a meaningful increase in
      cataract prevalence. However, due to the increased ALP serum levels and FEV1/FVC
      ratios among TNT workers, safety precautions are advised.

PMID- 22994932
TI  - Identifying and acquiring the contextual skills and knowledge for nursing
      practice in assisted reproductive technology: a grounded theory study.
AB  - AIMS AND OBJECTIVES: To identify the contextual knowledge and skills required for
      practice. BACKGROUND: Nursing practice in assisted reproductive technology (ART)
      makes a significant contribution to patient care. Despite this, the knowledge and
      skills integral to this area of practice have not been clearly articulated,
      particularly from an Australian perspective. DESIGN: A constructivist grounded
      theory design was used to gain the perspective of ART nurses in relation to how
      they understood their clinical practice as well as the issues and challenges that
      they faced. METHODS: Individual in-depth interviews were undertaken with 15
      registered nurses working in ART units across Australia. Constant comparative
      data analysis was used to determine the main categories. RESULTS: Contextual
      knowledge and skills was one category to emerge from this research, and this is
      the focus of this paper. The findings in respect of knowledge and skill included
      three main subcategories: required skills and knowledge; acquisition of skills
      and knowledge; and factors influencing acquisition. CONCLUSIONS: The role of the
      ART nurse which must be performed within the context and competency standards of
      nursing requires a framework that could define and contribute to specialised ART
      nursing practice standards. RELEVANCE TO CLINICAL PRACTICE: The nursing role is
      instrumental to effective ART treatment and care. The standard of clinical
      practice will depend in part on the ability of specialist nurses to articulate
      their practice, and their professional development needs to optimise quality and
      effectiveness. The results of this study demonstrate that contextual knowledge
      and skills are a key aspect of this specialised nursing role.

PMID- 22994933
TI  - Small-angle neutron-scattering studies of mixed micellar structures made of
      dimeric surfactants having imidazolium and ammonium headgroups.
AB  - Planar imidazolium cation based gemini surfactants [16-Im-n-Im-16], 2Br(-) (where
      n = 2, 3, 4, 5, 6, 8, 10, and 12), exhibit different morphologies and internal
      packing arrangements by adopting different supramolecular assemblies in aqueous
      media depending on their number of spacer methylene units (CH(2))(n). Detailed
      measurements of the small-angle neutron-scattering (SANS) cross sections from
      different imidazolium-based surfactant micelles in aqueous media (D(2)O) are
      reported. The SANS data, containing the information of aggregation behavior of
      such surfactants in the molecular level, have been analyzed on the basis of the
      Hayter and Penfold model for the macro ion solution to compute the interparticle
      structure factor S(Q) taking into account the screened Coulomb interactions
      between the dimeric surfactant micelles. The characteristic changes in the SANS
      spectra of the dimeric surfactant with n = 4 due to variation of temperature have
      also been investigated. These data are then compared with the SANS
      characterization data of the corresponding gemini micelles containing tetrahedral
      ammonium ion based polar headgroups. The critical micellar concentration of each
      surfactant micelle (cmc) has been determined using pyrene as an extrinsic
      fluorescence probe. The variation of cmc as a function of spacer chain length has
      been explained in terms of conformational variation and progressive looping of
      the spacer into the micellar interior upon increasing the n values. Small-angle
      neutron-scattering (SANS) cross sections from different mixed micelles composed
      of surfactants with ammonium headgroups, 16-A(0), [16-Am-n-Am-16], 2Br(-) (where
      n = 4), 16-I(0), and [16-Im-n-Im-16], 2Br(-) (where n = 4), in aqueous media
      (D(2)O) have also been analyzed. The aggregate composition matches with that
      predicted from the ideal mixing model.

PMID- 22994934
TI  - The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: a
      Children's Oncology Group report.
AB  - T-lymphoblastic leukaemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) are
      neoplasms derived from immature lymphoid cells of T-cell lineage. These neoplasms
      are biologically similar, but significant differences may exist between the two
      given their clinical differences. Although ample data regarding the
      immunophenotypic characterization T-ALL are available, there is a paucity of such
      data in children and adolescents with T-LBL. We used flow cytometry and/or
      immunohistochemistry to characterize the immunophenotypic profile of 180 children
      and adolescents with newly diagnosed T-LBL enrolled in the Children's Oncology
      Group 5971 study. Multiple T-cell, B-cell, myeloid, and other markers were
      evaluated. We identified diagnostically useful immunophenotypic features of T-LBL
      as well as distinct immunophenotypic subgroups, although none of these was
      statistically related to event-free or overall survival in this retrospective
      analysis. Further studies of biologically and immunophenotypically distinct
      subgroups of T-LBL, such as the early T-cell precursor phenotype, are warranted.

PMID- 22994936
TI  - Varicella-zoster immunization in pediatric liver transplant recipients: safe and
      immunogenic.
AB  - Varicella can have a severe course in immunosuppressed patients. Although
      prevention is fundamental, live-attenuated varicella-zoster (VZV) vaccine is not
      currently recommended in transplant recipients. Our aims were to (1) evaluate VZV
      immunity in pediatric liver transplant (LT) recipients; (2) immunize (two doses)
      seronegative patients post-LT; (3) monitor vaccine safety, (4) assess B and T
      cell vaccine responses. All patients followed at the Swiss National Pediatric LT
      Center were approached and 77/79 (97.5%) were enrolled (median age 7.8 years).
      Vaccine safety was monitored by standardized diary cards and phone calls. VZV
      specific serology and CD4(+)  T cells were assessed before and after
      immunization. Thirty-nine patients (51.1%) were seronegative including 14
      children immunized pre-LT. Thirty-six of 39 seronegative patients were immunized
      post-LT (median 3.0 years post LT). Local (54.8%) and systemic (64.5%) reactions
      were mild and transient. The frequency of VZV-specific CD4(+)  T cells and
      antibody titers increased significantly (respectively from 0.085% to 0.16%, p =
      0.04 and 21.0 to 1134.5 IU/L, p < 0.001). All children reached seroprotective
      titers and 31/32 (97%) patients assessed remained seroprotected at follow-up
      (median 1.7 years). No breakthrough disease was reported during follow-up (median
      4.1 years). Thereby, VZV vaccine appears to be safe, immunogenic and provide
      protection against disease in pediatric LT patients.

PMID- 22994935
TI  - Wear, bone density, functional outcome and survival in vitamin E-incorporated
      polyethylene cups in reversed hybrid total hip arthroplasty: design of a
      randomized controlled trial.
AB  - BACKGROUND: Aseptic loosening of total hip arthroplasties is generally caused by
      periprosthetic bone resorption due to tissue reactions on polyethylene wear
      particles. In vitro testing of polyethylene cups incorporated with vitamin E
      shows increased wear resistance. The objective of this study is to compare
      vitamin E-stabilized highly cross-linked polyethylene with conventional cross
      linked polyethylene in "reversed hybrid" total hip arthroplasties (cemented all
      polyethylene cups combined with uncemented femoral stems). We hypothesize that
      the adjunction of vitamin E leads to a decrease in polyethylene wear in the long
      term. We also expect changes in bone mineral density, less osteolysis, equal
      functional scores and increased implant survival in polyethylene cemented cups
      incorporated with vitamin E in the long-term. DESIGN: A double-blinded randomized
      controlled trial will be conducted. Patients to be included are aged under 70,
      suffer from non-inflammatory degenerative joint disease of the hip and are
      scheduled for a primary total hip arthroplasty. The study group will receive a
      reversed hybrid total hip arthroplasty with a vitamin E-stabilized highly cross
      linked polyethylene cemented cup. The control group will receive a reversed
      hybrid total hip arthroplasty with a conventional cross-linked polyethylene
      cemented cup. Radiological follow-up will be assessed at 6 weeks and at 1, 3, 5,
      7 and 10 years postoperatively, to determine polyethylene wear and osteolysis.
      Patient-reported functional status (HOOS), physician-reported functional status
      (Harris Hip Score) and patients' physical activity behavior (SQUASH) will also be
      assessed at these intervals. Acetabular bone mineral density will be assessed by
      dual energy X-ray absorptiometry (DEXA) at 6 weeks and at 1 year and 2 years
      postoperatively. Implant survival will be determined at 10 years postoperatively.
      DISCUSSION: In vitro results of vitamin E-stabilized polyethylene are promising,
      showing increased wear resistance. However, controlled clinical follow-up data
      are not available at this moment.This randomized controlled trial has been
      designed to determine wear, bone mineral density, functional outcome and survival
      in reversed hybrid total hip arthroplasty comparing cemented vitamin E-stabilized
      highly cross-linked polyethylene cups with cemented conventional cross-linked
      polyethylene cups. TRIAL REGISTRATION: Dutch Trial Registry NTR3049.

PMID- 22994937
TI  - Individual differences in decision making and reward processing predict changes
      in cannabis use: a prospective functional magnetic resonance imaging study.
AB  - Decision-making deficits are thought to play an important role in the development
      and persistence of substance use disorders. Individual differences in decision
      making abilities and their underlying neurocircuitry may, therefore, constitute
      an important predictor for the course of substance use and the development of
      substance use disorders. Here, we investigate the predictive value of decision
      making and neural mechanisms underlying decision making for future cannabis use
      and problem severity in a sample of heavy cannabis users. Brain activity during a
      monetary decision-making task (Iowa gambling task) was compared between 32 heavy
      cannabis users and 41 matched non-using controls using functional magnetic
      resonance imaging. In addition, within the group of heavy cannabis users,
      associations were examined between task-related brain activations, cannabis use
      and cannabis use-related problems at baseline, and change in cannabis use and
      problem severity after a 6-month follow-up. Despite normal task performance,
      heavy cannabis users compared with controls showed higher activation during wins
      in core areas associated with decision making. Moreover, within the group of
      heavy cannabis users, win-related activity and activity anticipating loss
      outcomes in areas generally involved in executive functions predicted change in
      cannabis use after 6 months. These findings are consistent with previous studies
      and point to abnormal processing of motivational information in heavy cannabis
      users. A new finding is that individuals who are biased toward immediate rewards
      have a higher probability of increasing drug use, highlighting the importance of
      the relative balance between motivational processes and regulatory executive
      processes in the development of substance use disorders. 

PMID- 22994938
TI  - Non-adrenergic, non-cholinergic, non-purinergic contractions of the
      urothelium/lamina propria of the pig bladder.
AB  - Acetylcholine, and to a lesser extent ATP, mediates neurogenic contractions of
      bladder smooth muscle. Recently, the urothelium and lamina propria have also been
      shown to have contractile properties, but the neurotransmitters involved in
      mediating responses to nerve stimulation have not been investigated. Isolated
      strips of porcine urothelium with lamina propria were electrically field
      stimulated and contractions recorded. Drugs interfering with neurotransmission
      were then employed to identify which neurotransmitters mediated responses. Strips
      of urothelium/lamina propria developed spontaneous contractions with a frequency
      of 3.5+/-0.1 cycles min-1 and amplitude of 0.84+/-0.06 g. Electrical field
      stimulation at 5, 10, and 20 Hz resulted in frequency-related contractions
      (1.13+/-0.36 g, 1.59+/-0.46 g and 2.20+/-0.53 g, respectively, n=13), and these
      were reduced in the presence of tetrodotoxin (1 MUm) by 77+/-20% at 5 Hz, 79+/-7%
      at 10 Hz and 74+/-12% at 20 Hz (all P<0.01), indicating they were predominantly
      neurogenic in nature. Neither the muscarinic antagonist atropine (10 MUm), the
      adrenergic neurone blocker guanethidine (10 MUm) nor desensitization of the
      purinergic receptors with alpha,beta-methylene ATP (10 MUm) affected the
      contractile amplitude. Similarly, responses were not affected by the nitric oxide
      synthase inhibitor L-NNA (100 MUm) or drugs that interfere with peptide
      neurotransmission (capsaicin, NK2 antagonist GR159897, protease inhibitors). In
      conclusion, electrical depolarization of the nerves present in the porcine
      urothelium/lamina propria results in frequency-dependent contractions, which are
      predominantly neurogenic in nature. These contractions are resistant to drugs
      that inhibit the adrenergic, cholinergic and purinergic systems. The
      neurotransmitter involved in the responses of this tissue is therefore unknown
      but does not appear to be a peptide.

PMID- 22994939
TI  - Captopril avoids hypertension, the increase in plasma angiotensin II but
      increases angiotensin 1-7 and angiotensin II-induced perfusion pressure in
      isolated kidney in SHR.
AB  - We investigated captopril effects, an ACE inhibitor, on hypertension development,
      on Ang II and Ang-(1-7) plasma concentrations, on Ang II-induced contraction in
      isolated kidneys, and on kidney AT1R from spontaneously hypertensive (SHR) rats.
      Five weeks-old SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30
      mg/kg/day, in drinking water for 2 or 14 weeks. Systolic blood pressure (SBP) was
      measured, and isolated kidneys were tested for perfusion pressure and AT1R
      expression; while Ang II and Ang-(1-7) concentrations were determined in plasma.
      Captopril did not modify SBP in WKY rats and avoided its increase as SHR aged.
      Plasma Ang-II concentration was ~4-5 folds higher in SHR rats, and captopril
      reduced it (P<0.05); while captopril increased Ang-(1-7) by ~2 fold in all rat
      groups. Captopril increased Ang II-induced pressor response in kidneys of WKY and
      SHR rats, phenomenon not observed in kidneys stimulated with phenylephrine, a
      alpha1-adrenoceptor agonist. Captopril did not modify AT1R in kidney cortex and
      medulla among rat strains and ages. Data indicate that captopril increased Ang II
      induced kidney perfusion pressure but not AT1R density in kidney of WKY and SHR
      rats, due to blockade of angiotensin II synthesis; however, ACE inhibitors may
      have other actions like activating signaling processes that could contribute to
      their diverse effects.

PMID- 22994940
TI  - Health-related quality of life in diabetic people with different vascular risk.
AB  - BACKGROUND: The number of papers on the health related quality of life of
      patients with DM has grown in recent years but fewer studies have drawn
      comparisons between diabetic persons and the general population considering
      different risk groups. The aim of this study is to examine health related quality
      of life (HRQOL) in people with diabetes mellitus (DM) and to analyze the
      differences in HRQOL adjusting by vascular risk. METHODS: The data used in this
      analysis was obtained from the responses of 15,926 individuals who participated
      in the 2006 Catalonia Health Survey. Our analysis provides a number of
      multivariate statistical models designed for studying HRQOL, based on the EQ-5D
      questionnaire, controlling for demographic factors of survey participants and
      variables that identify diagnosed illnesses and health problems. RESULTS: Our
      findings suggest there is a significant, moderate negative relationship between
      DM and HRQOL in comparison with non diabetic people (absolute value of the
      coefficient ranges between -0.04 and -0.054 points on a scale of 1). A further
      analysis of subgroups reveals that diabetics who have not had vascular risk
      factors neither vascular diseases do not have a diminished HRQOL when compared to
      the non-diabetic population in general, when other factors are controlled for. In
      contrast, a comparison of diabetics and non-diabetics who exhibit vascular
      disease or risk factors for vascular disease reveals HRQOL is significantly
      diminished to a greater extent for those with diabetes (between 0.152 and 0.175
      points loss when comparing a non-diabetic person with a diabetic with vascular
      disease). Also, HRQOL in diabetic patients who have additional risk factors or a
      vascular disease are lower than people non-diabetic who have additional risk
      factors or a vascular disease. When we focus our analysis to the EQ-5D
      dimensions, we observe that diabetic persons who are neither at risk for nor have
      a diagnosed vascular disease are no more likely than non-diabetics to report
      problems. However, diabetic patients who have additional risk factors for
      vascular disease or a diagnosed vascular disease are significantly more likely to
      report moderated or severe problems in 4 of the 5 dimensions of EQ-5D.
      CONCLUSIONS: The HRQOL of a person who has diabetes is not necessarily lower than
      for a non-diabetic. Control of risk factors associated to vascular diseases is a
      key factor for an enhanced quality of life. Vascular disease or risk factors for
      vascular disease, on the other hand, are associated with a significantly
      diminished quality of life for diabetic persons.

PMID- 22994941
TI  - Phase I study of miriplatin combined with transarterial chemotherapy using CDDP
      powder in patients with hepatocellular carcinoma.
AB  - BACKGROUND: There is no standard therapeutic procedure for the hepatocellular
      carcinoma (HCC) in patients with poor hepatic reserve function. With the approval
      of newly developed chemotherapeutic agent of miriplatin, we have firstly
      conducted the phase I study of CDDP powder (DDP-H) and miriplatin combination
      therapy and reported its safety and efficacy for treating unresectable HCC in
      such cases. To determine the maximum tolerated dose (MTD) and dose-limiting
      toxicity (DLT) for the combination of transarterial oily chemoembolization (TOCE)
      and transarterial chemotherapy (TAC) using miriplatin and DDP-H for treating
      unresectable hepatocellular carcinoma (HCC). METHODS: Transarterial chemotherapy
      using DDP-H was performed through the proper hepatic artery targeting the HCC
      nodules by increasing the dose of DDP-H (35-65 mg/m(2)) followed by targeting the
      HCC nodules by transarterial oily chemoembolization with miriplatin. RESULTS: A
      total of nine patients were enrolled in this study and no DLT was observed with
      any dose of DDP-H in all cases in whom 80 mg (median, 18-120) miriplatin was
      administered. An anti-tumour efficacy rating for partial response was obtained in
      one patient, while a total of four patients (among eight evaluated) showed stable
      disease response, leading to 62.5% of disease control rate. The pharmacokinetic
      results showed no further increase in plasma platinum concentration following
      miriplatin administration. CONCLUSION: Our results suggest that a combination of
      DDP-H and miriplatin can be safely administered up to their respective MTD for
      treating HCC. TRIAL REGISTRATION: This study was registered with the University
      Hospital Medical Information Network Clinical Trials Registry (UMIN
      CTR000003541).

PMID- 22994944
TI  - Evolutionary adaptation of plant annexins has diversified their molecular
      structures, interactions and functional roles.
AB  - Annexins are an homologous, structurally related superfamily of proteins known to
      associate with membrane lipid and cytoskeletal components. Their involvement in
      membrane organization, vesicle trafficking and signaling is fundamental to
      cellular processes such as growth, differentiation, secretion and repair.
      Annexins exist in some prokaryotes and all eukaryotic phyla within which plant
      annexins represent a monophyletic clade of homologs descended from green algae.
      Genomic, proteomic and transcriptomic approaches have provided data on the
      diversity, cellular localization and expression patterns of different plant
      annexins. The availability of 35 complete plant genomes has enabled systematic
      comparative analysis to determine phylogenetic relationships, characterize
      structures and observe functional specificity between and within individual
      subfamilies. Short amino termini and selective erosion of the canonical type 2
      calcium coordinating sites in domains 2 and 3 are typical of plant annexins. The
      convergent evolution of alternate functional motifs such as 'KGD', redox
      sensitive Cys and hydrophobic Trp/Phe residues argues for their functional
      relevance and contribution to mechanistic diversity in plant annexins. This
      review examines recent findings and advances in plant annexin research with
      special focus on their structural diversity, cellular and molecular interactions
      and their potential integrated functions in the broader context of physiological
      responses.

PMID- 22994945
TI  - Consistency of assessments and willingness to pay for a reduction in morning
      symptoms over time in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To determine the variation in morning symptoms and in the
      corresponding monetary equivalents assigned to their reduction. METHODS: The
      sampled (n = 100) rheumatoid arthritis (RA) patients were interviewed twice by a
      trained interviewer using the same interview, 2 weeks apart. Patients assessed
      fatigue, pain, and severity of morning stiffness (MS) on waking up and after
      maximum improvement on a numeric rating scale (NRS). Patients estimated the
      duration of MS in minutes and reported the number of tender and swollen joints.
      Patients were also asked to estimate how much they would be willing to pay on a
      daily basis if pain, duration of MS, and severity of MS when waking up could be
      reduced by 25, 50, 75, and 100%. Weighted averages of the monetary assessments
      for symptom reduction were computed. RESULTS: On average, the NRS values at the
      first and second assessments were close to each other, except for fatigue and
      pain, which were significantly lower (p < 0.01) in the second assessment. There
      was limited within-patient variation, with the majority of symptom assessments
      within a range of +/-10%. Weighted average willingness-to-pay (WTP) estimates
      were consistent across time points for reduction in pain and MS severity and
      duration. Changes in symptom assessments were reflected in the WTP estimates.
      CONCLUSIONS: The duration and severity of MS seemed to be more consistent over
      time than pain and fatigue. WTP estimates and their changes corresponded closely
      to changes in symptom assessments.

PMID- 22994946
TI  - Cardiomyocyte apoptosis in ischaemia-reperfusion due to the exogenous oxidants at
      the time of reperfusion.
AB  - Various studies performed on different models have demonstrated that apoptosis
      occurs in ischaemic-reperfused myocardium in vivo; however, the individual
      contribution of ischaemia and reperfusion to CMC (cardiomyocyte) apoptosis
      remains uncertain. We have determined the main inducer of CMC apoptosis in
      ischaemia-reperfusion by exposing CMCs to either 30 min ischaemia followed by
      reperfusion or to 25-OH-cholesterol (25-hydroxycholesterol) for 1-3 days. Both
      ischaemia-reperfusion and exogenous oxidants increased the Bax/Bcl-2 ratio, a
      favourable effect for the apoptotic process. However, apoptosis was not observed
      in ischaemic CMCs in the absence of reperfusion. Moreover, reperfusion after 30
      min ischaemia did not make an important contribution to CMC apoptosis in culture
      in terms of caspase 3 activation. In contrast, 25-OH-cholesterol promoted CMC
      apoptosis by a caspase 3-dependent mechanism that involved the transcriptional
      activation of the pro-apoptotic protein, Bax and post-translational degradation
      of the anti-apoptotic protein, Bcl-2. From these results, we conclude that CMC
      apoptosis is not induced by ischaemia per se, but by the oxidants from the
      surrounding environment at the time of reperfusion. These exogenous oxidants
      exacerbate the alterations induced by ischaemia and complete the apoptotic
      process at the time when ATP and glucose levels are restored.

PMID- 22994947
TI  - High parathyroid hormone, but not low vitamin D concentrations, expose elderly
      inpatients to hypertension.
AB  - AIM: Serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD)
      concentrations might contribute to blood pressure (BP) levels. Mixed results in
      previous literature could be due to the failure to consider both these hormones
      concurrently, despite their long-known relationship. Our objective was to examine
      the association of serum intact PTH and 25OHD concentrations with BP levels
      amongst older inpatients, while accounting for each other. METHODS: The
      participants were 284 Caucasian older inpatients with no suspicion of primary
      hyperparathyroidism (mean age 85.87 +/- 5.90 years; 65.8% female) admitted to the
      geriatric acute care unit of Angers University Hospital, France. They were
      divided into two groups according to the existence of hypertension (i.e. systolic
      blood pressure [SBP] >140 mmHg, or diastolic blood pressure [DBP] >90 mmHg). Age,
      sex, numbers of chronic diseases and of drugs taken daily, use of
      antihypertensive or corticosteroid drugs and of calcium supplements/vitamin D,
      thyroid-stimulating hormone and albumin concentrations, creatinine clearance, and
      season tested were used as covariables. RESULTS: Hypertensive participants
      (n=106) had higher intact PTH concentrations than normotensive patients
      (P=0.044). There was a positive linear association of BP with intact PTH
      concentrations (adjusted beta=0.08, P=0.015 for SBP; adjusted beta=0.05, P=0.044
      for DBP), but not with vitamin D. Serum intact PTH concentration, unlike 25OHD,
      was associated with hypertension (adjusted OR 1.01, P=0.038). CONCLUSIONS:
      Irrespective of 25OHD, PTH was associated with hypertension by increasing both
      SBP and DBP.

PMID- 22994948
TI  - Nocturnal colonization behavior of blowflies (Diptera: Calliphoridae) in
      southeastern Australia.
AB  - Worldwide research into nocturnal colonization by blowflies has produced many
      contradictory findings, prompting investigation specific to southeastern
      Australia. Initial experiments showed that blowfly colonization begins shortly
      after sunrise and continues until sunset; nocturnal colonization never occurred.
      Colonization peaks occurred at mid-morning, midday, and in the hours preceding
      sunset. In an additional experiment, wild blowflies were captured and placed in
      cages with colonization medium supplied nocturnally. Colonization occurred on
      four of five nights, and Calliphora augur (Fabricius) (Diptera: Calliphoridae)
      was the main species colonizing baits nocturnally. Results suggest that
      colonization is most likely to occur during warm weather and when flies are able
      to walk or crawl to bait. In particular, blowflies trapped within a confined
      space (such as a room or car) with warmer-than-ambient temperature may be
      stimulated to colonize nearby remains. Entomologists should consider these
      findings when estimating minimum postmortem interval under these environmental
      conditions.

PMID- 22994949
TI  - Time of acquisition of HCV infection in renal transplant recipients: a major
      prognostic factor for disease progression.
AB  - BACKGROUND: This study aims to identify crucial factors affecting the evolution
      of liver disease in HCV-infected renal transplant recipients. METHODS: Forty-two
      HCV-infected recipients with known time of HCV acquisition were followed up for a
      mean (SD) of 7.6 +/- 3.4 yr after transplantation with consecutive liver
      biopsies. Hepatitis progression was defined by: a) fibrosis progression >= 0.2
      stages/yr and/or b) development of a cholestatic syndrome. RESULTS: Twenty-three
      patients (54.8%) displayed benign and 19 (45.2%) aggressive hepatitis
      progression. Hepatitis course was aggressive in 9.1% and 85% of the patients
      infected pre- and peri/post-transplantation, respectively (p < 0.001). In
      multivariate analysis, patients who acquired HCV infection peri- or after
      transplantation had an increased risk of an adverse outcome compared with those
      infected before transplantation (p = 0.001). HCV RNA levels at the time of first
      liver biopsy were lower in patients showing a benign course compared with those
      with aggressive evolution (p = 0.052). CONCLUSIONS: Time of acquisition of HCV
      infection is a major prognostic factor for hepatitis progression in the setting
      of renal transplantation. Immunosuppression was found to be determinant in the
      progression of HCV infection acquired peri- or post-transplantation. High viral
      load seems to be crucial in the pathogenetic process.

PMID- 22994950
TI  - Clinical evaluation of a dioic acid-based formulation on facial skin in an Indian
      population.
AB  - The aim of this work was to investigate the effects of 1,18-octadecen-9-dioic
      acid (dioic acid) and a Rumex occidentalis extract complex for their skin
      lightening action in an Indian population. Prior to the clinical study, the
      efficacy of dioic as an inhibitor of melanogenesis was confirmed on dark
      pigmented human melanocytes. As part of a 12-week vehicle-controlled clinical
      study, the skin-lightening effect of a test product containing 1% dioic acid, 2%
      of a Rumex occidentalis extract and sunscreens (SPF 15) was assessed on the
      facial skin of 71 Indian female volunteers. Change in skin colour was monitored
      by (A) Chroma Meter(r) measurement (L*, a*, b*) and Individual Typology Angle
      (ITA) calculation and (B) Visual grading of standardized photographs by a
      dermatologist. Colorimetric measurements on volunteers' cheeks showed a
      significant increase of L* and ITA compared to baseline after 4, 8 and 12 weeks
      of test product application. For both L* and ITA measurements, changes were
      significantly different than the SPF 15-containing vehicle at weeks 4 and 12.
      These results were confirmed by the dermatological visual grading. The overall
      skin-lightening action of the test product was beyond the one observed with the
      SPF 15 vehicle. These findings show that a dioic acid and Rumex occidentalis
      complex deliver a significant skin-lightening effect on facial skin in an Indian
      population.

PMID- 22994951
TI  - Representative volume element to estimate buckling behavior of graphene/polymer
      nanocomposite.
AB  - The aim of the research article is to develop a representative volume element
      using finite elements to study the buckling stability of graphene/polymer
      nanocomposites. Research work exploring the full potential of graphene as filler
      for nanocomposites is limited in part due to the complex processes associated
      with the mixing of graphene in polymer. To overcome some of these issues, a
      multiscale modeling technique has been proposed in this numerical work. Graphene
      was herein modeled in the atomistic scale, whereas the polymer deformation was
      analyzed as a continuum. Separate representative volume element models were
      developed for investigating buckling in neat polymer and graphene/polymer
      nanocomposites. Significant improvements in buckling strength were observed under
      applied compressive loading when compared with the buckling stability of neat
      polymer.

PMID- 22994952
TI  - Bacterial inclusion bodies: an emerging platform for drug delivery and cell
      therapy.

PMID- 22994953
TI  - Nanostructured porous silicon materials: potential candidates for improving drug
      delivery.

PMID- 22994954
TI  - Nanoparticles: the future for platinum drugs or a research red herring?

PMID- 22994956
TI  - Towards the clinic: intelligent design of nanomedicines for cancer treatment.

PMID- 22994957
TI  - Nanostructuring molecular materials as particles and vesicles for drug delivery,
      using compressed and supercritical fluids.
AB  - The structuring of synthetic and biological therapeutic actives as micro- and
      nano-particulate materials is a widely accepted formulation strategy to improve
      efficacy and reduce the toxicity of drugs. However, the development of efficient
      production platforms that enable the formulation of these nanomedicines at an
      industrial scale and with the quality requirements imposed by regulatory agencies
      remains a challenge. In this framework, compressed fluid-based methods are
      promising technologies for the controlled and reproducible preparation of uniform
      micro- and nano-particulate nanomedicines at a large scale. This review provides
      an overall but practical knowledge about what has been achieved so far in the
      field of compressed fluids applied to the preparation of solid micro- and
      nanoparticles and vesicles as drug delivery systems. In addition, recent examples
      of application of these technologies to the production of polymeric
      nanostructured microparticles highly loaded with gentamicin and to the
      preparation of uniform cholesterol-rich vesicular systems are explained.

PMID- 22994958
TI  - Clues for biomimetics from natural composite materials.
AB  - Bio-inspired material systems are derived from different living organisms such as
      plants, arthropods, mammals and marine organisms. These biomaterial systems from
      nature are always present in the form of composites, with molecular-scale
      interactions optimized to direct functional features. With interest in replacing
      synthetic materials with natural materials due to biocompatibility,
      sustainability and green chemistry issues, it is important to understand the
      molecular structure and chemistry of the raw component materials to also learn
      from their natural engineering, interfaces and interactions leading to durable
      and highly functional material architectures. This review will focus on
      applications of biomaterials in single material forms, as well as biomimetic
      composites inspired by natural organizational features. Examples of different
      natural composite systems will be described, followed by implementation of the
      principles underlying their composite organization into artificial bio-inspired
      systems for materials with new functional features for future medicine.

PMID- 22994960
TI  - Iron oxide-based nanostructures for MRI and magnetic hyperthermia.
AB  - Many different nanostructures have been developed for biomedical applications to
      date. Among them, iron oxide nanoparticles have been very prominent in MRI in
      diagnostic radiology. Nowadays, nanoparticle-based therapeutic applications have
      gained increased interest, leading to the development of a great variety of
      different and, in parts, sophisticated nanoparticle formulations. Whereas
      nanotherapy has been confined to the preclinical phase, magnetic hyperthermia has
      entered into the clinical phase via controlled studies in patients. Owing to the
      versatility of nanoparticles, researchers envision the combination of multiple
      modalities (e.g., targeting, diagnostics and therapy) to one carrier.
      Nevertheless, such approaches have been challenging due to the necessity of the
      adaptation of at least partially counteracting parameters between the different
      modalities, which will be analyzed in this review.

PMID- 22994959
TI  - Magnetic nanoparticle-based approaches to locally target therapy and enhance
      tissue regeneration in vivo.
AB  - Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic
      field gradient to exert a force on these particles have been used in a wide range
      of biomedical applications. This review is focused on drug targeting applications
      that require penetration of a cellular barrier as well as strategies to improve
      the efficacy of targeting in these biomedical applications. Another focus of this
      review is regenerative applications utilizing tissue engineered scaffolds
      prepared with the aid of magnetic particles, the use of remote actuation for
      release of bioactive molecules and magneto-mechanical cell stimulation, cell
      seeding and cell patterning.

PMID- 22994962
TI  - Empiric antibiotics and outcomes of children hospitalized with eczema herpeticum.
AB  - Although patients with eczema herpeticum often receive antibiotics for presumed
      bacterial coinfection, the effect of empiric antibiotic therapy is unknown. Our
      objective therefore was to determine the association between empiric antibiotics
      and outcomes in children hospitalized with eczema herpeticum. We conducted a
      multicenter retrospective cohort study of 1,150 children ages 2 months to 17
      years admitted with eczema herpeticum between January 1, 2001, and March 31,
      2010, to 42 tertiary care children's hospitals in the Pediatric Health
      Information System. All patients received antibiotics during the hospitalization.
      Multivariable linear regression models determined the association between empiric
      antibiotic therapy and the main outcome measure: hospital length of stay (LOS).
      There were no deaths during the study period. Receipt of empiric antibiotics was
      not associated with a change in the LOS on unadjusted or multivariable analysis.
      The class of empiric antibiotic was not associated with the LOS except for
      receipt of vancomycin, which was associated with a longer LOS (21% adjusted
      longer LOS, 95% confidence interval (CI) = 8-35%; p = 0.001). When restricted to
      patients with a bloodstream infection, receipt of empiric antibiotics was
      associated with a 51% adjusted shorter LOS (95% CI = -24 to -68%; p = 0.002). In
      children hospitalized with eczema herpeticum, empiric antibiotic therapy was not
      associated with a shorter LOS overall, but was associated with a shorter LOS in
      patients with a bloodstream infection. These findings highlight the importance of
      early recognition of systemic bacterial illness in children with eczema
      herpeticum. Empiric antibiotics did not affect mortality, which is low.

PMID- 22994963
TI  - Relationship between palate-vomer development and maxillary growth in submucous
      cleft palate patients.
AB  - Objective : Experimental and clinical findings suggest that the vomer is involved
      in facial development and might contribute to the short and retrusive maxilla in
      cleft patients. The aim of this study was to investigate the relationship between
      vomer development and maxillary growth in unoperated submucous cleft palate
      (SMCP) patients. Design : Retrospective cohort study. Participants : Thirty
      unoperated SMCP patients were included. The criteria for clinical diagnosis were:
      bifid uvula, a translucent zone in the midline of the soft palate, and a
      touchable "V" notch on the posterior border of the bony palate. There were 19
      female and 11 male patients, with an age range from 3 to 25 years. Interventions
      : All patients were imaged using spiral computed tomography (CT) while in centric
      occlusion before the surgeries. Main Outcome Measures : Three-dimensional (3D)
      reconstruction models were created, and dentoalveolar relationships were rated by
      three experienced doctors according to the GOSLON score principles. The patients
      then were divided into three groups: 1 - normal occlusion, 2 - edge-to-edge bite,
      and 3 - crossbite. The vomer-palate fusion rate was calculated on 3D CT images
      and represented the vomer development. Results : The sagittal extent of the
      palatal cleft and the malformation of vomer in SMCP were greatly varied. The
      vomer-palate fusion rate in the crossbite group (occlusal score = 3) was
      significantly lower than that in the normal occlusion group (P = .027).
      Conclusions : Our findings suggest that correlation exists between vomer
      development and sagittal maxillary growth in unoperated SMCP patients. 

PMID- 22994965
TI  - Consistent divergence times and allele sharing measured from cross-species
      application of SNP chips developed for three domestic species.
AB  - Recent advances in technology facilitated development of large sets of genetic
      markers for many taxa, though most often model or domestic organisms. Cross
      species application of genomic technologies may allow for rapid marker discovery
      in wild relatives of taxa with well-developed resources. We investigated returns
      from cross-species application of three commercially available SNP chips (the
      OvineSNP50, BovineSNP50 and EquineSNP50 BeadChips) as a function of divergence
      time between the domestic source species and wild target species. Across all
      three chips, we observed a consistent linear decrease in call rate (~1.5% per
      million years), while retention of polymorphisms showed an exponential decay.
      These results will allow researchers to predict the expected amplification rate
      and polymorphism of cross-species application for their taxa of interest, as well
      as provide a resource for estimating divergence times.

PMID- 22994964
TI  - A simple protocol for the subcellular fractionation of skeletal muscle cells and
      tissue.
AB  - BACKGROUND: We describe a method for subcellular fractionation of mouse skeletal
      muscle, myoblast and myotubes to obtain relatively pure fractions of nuclear,
      cytosolic and mitochondrial compartments. Fractionation allows the analysis of a
      protein of interest (or other cellular component) based on its subcellular
      compartmental distribution and can also generate molecular information about the
      state of a cell and/or tissue and how the distribution of a protein may differ
      between different cellular compartments, tissues or cell types, in response to
      treatments or ageing. FINDINGS: The described method was specifically developed
      for skeletal muscle and proliferating/differentiated muscle cells. The purity of
      the different fractions, representing the cytoplasmic, mitochondrial and nuclear
      subcellular compartments was validated by western blot analysis of "house-keeper"
      marker proteins specific for each cellular compartment. CONCLUSION: This low cost
      method allowed the mitochondrial, cytoplasmic and nuclear subcellular
      compartments from the same starting muscle samples to be rapidly and
      simultaneously isolated with good purity and without the use of an
      ultracentrifuge. This method permits samples to be frozen at -80 degrees C for
      future analysis and/or additional processing at a later date.

PMID- 22994966
TI  - Assessment of ventricular electrophysiological characteristics at periinfarct
      zone of postmyocardial infarction in rabbits following stellate ganglion block.
AB  - Assessment of Ventricular Electrophysiological Characteristics. INTRODUCTION: The
      aim of this study was to investigate the characteristics of ventricular
      electrophysiology following stellate ganglion block (SGB) at periinfarct zone in
      rabbits with myocardial infarction (MI). METHODS AND RESULTS: Sixty-four rabbits
      were randomly assigned to 2 groups: MI (n = 32), ligation of the anterior
      descending coronary and sham operation (SO) (n = 32), without coronary ligation.
      Both MI and SO groups were divided into 4 subgroups according to right or left
      SGB and corresponding control (n = 8, each). After 8 weeks, 90% of monophasic
      action potential duration (MAPD90) of epicardium, midmyocardium and endocardium,
      transmural dispersion of repolarization (TDR), effective refractory period (ERP),
      and ventricular fibrillation threshold (VFT) were measured at the infarct border
      zone (MI group) and corresponding zone (SO group) following SGB. For SGB, 0.5 mL
      of 0.25% bupivacaine was used. Compared with the corresponding control group, in
      both the MI and SO groups, left SGB (LSGB) prolonged the MAPD90 of the 3 layers,
      reduced TDR, and increased ERP and VFT (P < 0.05). However, right SGB (RSGB)
      shortened MAPD90, increased TDR, and reduced ERP and VFT (P < 0.05). CONCLUSION:
      The results of this study demonstrate that LSGB can increase the
      electrophysiological stability of ventricular myocardium.

PMID- 22994968
TI  - Activity assay of epidermal growth factor receptor tyrosine kinase inhibitors in
      triple-negative breast cancer cells using peptide-conjugated magnetic beads.
AB  - Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast
      cancer with limited treatment options. Epidermal growth factor receptor I (EGFR)
      has emerged as a promising target in TNBC. Limited success of the EGFR kinase
      inhibiting small molecules in clinical trials may be attributed in part to
      inaccuracy in identifying EGFR signatures in patient tumors. In light of the
      absence of a simple correlation between EGFR expression and its degree of
      activation, a simple and reliable tool that can quantify EGFR kinase activity in
      tumor samples may be of therapeutic value in predicting patient-specific EGFR
      targeted therapies. This study reports the development of an assay that can
      quantitatively profile EGFR kinase activities and inhibitor sensitivities in TNBC
      cell lysates by using peptide reporters covalently tethered to magnetic beads in
      a controlled orientation. The use of magnetic beads provides rapid sample
      handling and easy product isolation. The potential of this approach was
      demonstrated by screening a set of five clinically relevant EGFR tyrosine kinase
      inhibitors. Formatted for microwell plates, this magnetic bead-based kinase assay
      may be used as a complementary approach for direct high-throughput screening of
      small molecule inhibitors.

PMID- 22994969
TI  - Mesh-loosening quantification of inhibition of angiogenic tube formation through
      image analysis.
AB  - Angiogenesis is a key step in tumor development, and anti-angiogenesis processes
      are important for drug discovery and development. The dose-response relationship
      for an inhibitor is studied using images of endothelial cells captured in vitro
      by Matrigel assay. In order to improve the quantification of anti-angiogenic
      processes for faithful synchronization with continuous variation of an inhibitor
      dose, we have developed an automated image analysis method-mesh-loosening
      analysis-to evaluate the disruption of tube formation from endothelial cells. The
      method is based on numerical and morphological changes of mesh regions surrounded
      by tubes and perceived by considering the spaces between the tubes rather than
      the tubes themselves. The anti-angiogenic effect of suramin is analyzed
      comprehensively using four attributes obtained from the mesh regions. The
      relation between the dose of suramin and response shows an exponential curve that
      can be approximated as a sigmoid function, even though human assessments yield
      strong inhibition at moderate doses. The calculated half-minimal inhibitory
      concentration was in agreement with prior published reports. The results show
      that mesh-loosening analysis is useful and appropriate for screening applications
      that need precise and comprehensive quantification of the anti-angiogenic process
      to compensate for the inadequacy of human assessment. Feasibility study with
      shikonin shows the robustness of the mesh-loosening analysis.

PMID- 22994967
TI  - Prototype for automatable, dielectrophoretically-accessed intracellular membrane
      potential measurements by metal electrodes.
AB  - Functional access to membrane proteins, for example, ion channels, of individual
      cells is an important prerequisite in drug discovery studies. The highly
      sophisticated patch-clamp method is widely used for electrogenic membrane
      proteins, but is demanding for the operator, and its automation remains
      challenging. The dielectrophoretically-accessed, intracellular membrane-potential
      measurement (DAIMM) method is a new technique showing high potential for
      automation of electrophysiological data recording in the whole-cell
      configuration. A cell suspension is brought between a mm-scaled planar electrode
      and a MUm-scaled tip electrode, placed opposite to each other. Due to the
      asymmetric electrode configuration, the application of alternating electric
      fields (1-5 MHz) provokes a dielectrophoretic force acting on the target cell. As
      a consequence, the cell is accelerated and pierced by the tip electrode, hence
      functioning as the internal (working) electrode. We used the light-gated cation
      channel Channelrhodopsin-2 as a reporter protein expressed in HEK293 cells to
      characterize the DAIMM method in comparison with the patch-clamp technique.

PMID- 22994970
TI  - The use of multi-sensory interventions to manage dementia-related behaviours in
      the residential aged care setting: a survey of one Australian state.
AB  - AIMS AND OBJECTIVES: To describe the use of multi-sensory interventions in
      residential aged care services (RACS) for the management of dementia-related
      behaviours in residential aged care in Victoria, Australia. BACKGROUND: The
      popularity of multi-sensory interventions has spread worldwide, including for use
      in residential aged care, despite limited evidence to support their efficacy.
      DESIGN: This study reports the findings of the first stage of a two-stage project
      that was undertaken to describe and evaluate the use of multi-sensory
      interventions for the management of dementia-related behaviours in all
      residential aged care facilities in Victoria, Australia. METHODS: A computer
      assisted telephone interview survey was developed and administered to residential
      aged care facilities in Victoria, Australia, to collect descriptive data on the
      use of multi-sensory interventions for the management of dementia-related
      behaviours. RESULTS: A diverse and eclectic range of multi-sensory interventions
      are currently being used by residential aged care facilities. The findings
      suggest the use of multi-sensory interventions are used in an ad hoc manner, and
      there is no universal definition of multi-sensory interventions, little formal
      training for staff administering the interventions and no guideline for their
      use, nor evaluation of their impact on residents' behaviour. CONCLUSION: Multi
      sensory interventions have been widely adopted for use in RACS in Victoria,
      Australia, and are currently being used without formal guidelines and little
      evidence to support their use in clinical practice. RELEVANCE TO CLINICAL
      PRACTICE: In the absence of a formal definition of what constitutes a multi
      sensory intervention, training for staff and careful assessment and monitoring of
      residents who receive multi-sensory interventions, we recommend further research
      and development of policy and procedures to safe guard the use of multi-sensory
      interventions for people with dementia.

PMID- 22994971
TI  - Guidelines for the investigation and management of mantle cell lymphoma.

PMID- 22994972
TI  - Attending work or not when sick - what makes the decision? A qualitative study
      among car mechanics.
AB  - BACKGROUND: High prevalence of sickness absence in countries with generous
      welfare schemes has generated debates on mechanisms that may influence workers'
      decisions about calling in sick for work. Little is known about the themes at
      stake during the decision-making process for reaching the choice of absence or
      attendance when feeling ill. The aim of the study was to examine decisions of
      absence versus attendance among car mechanics when feeling ill. METHODS:
      Interviews with 263 male car mechanics from 19 companies were used for the study,
      analysed by systematic text condensation and presented as descriptions and
      quotations of experiences and opinions. RESULTS: Three major themes were at stake
      during the decision-making process: 1) Experienced degree of illness, focusing on
      the present health condition and indicators of whether you are fit for work or
      not; 2) daily life habits, where attending work was a daily routine, often
      learned from childhood; 3) the importance of the job, with focus on the
      importance of work, colleagues, customers and work environment. CONCLUSIONS: The
      car mechanics expressed a strong will to attend work in spite of illness.
      Knowledge about attitudes and dilemmas in reaching the decision regarding
      sickness absence or sickness attendance is useful in the prevention of sickness
      absence.

PMID- 22994973
TI  - Peptidoglycan maturation enzymes affect flagellar functionality in bacteria.
AB  - The flagellar machinery is a highly complex organelle composed of a free rotating
      flagellum and a fixed stator that converts energy into movement. The assembly of
      the flagella and the stator requires interactions with the peptidoglycan layer
      through which the organelle has to pass for externalization. Lytic
      transglycosylases are peptidoglycan degrading enzymes that cleave the sugar
      backbone of peptidoglycan layer. We show that an endogenous lytic
      transglycosylase is required for full motility of Helicobacter pylori and
      colonization of the gastric mucosa. Deficiency of motility resulted from a
      paralysed phenotype implying an altered ability to generate flagellar rotation.
      Similarly, another Gram-negative pathogen Salmonella typhimurium and the Gram
      positive pathogen Listeria monocytogenes required the activity of lytic
      transglycosylases, Slt or MltC, and a glucosaminidase (Auto), respectively, for
      full motility. Furthermore, we show that in absence of the appropriate lytic
      transglycosylase, the flagellar motor protein MotB from H. pylori does not
      localize properly to the bacterial pole. We present a new model involving the
      maturation of the surrounding peptidoglycan for the proper anchoring and
      functionality of the flagellar motor.

PMID- 22994975
TI  - The 2010 American college of rheumatology fibromyalgia survey diagnostic criteria
      and symptom severity scale is a valid and reliable tool in a French speaking
      fibromyalgia cohort.
AB  - BACKGROUND: Fibromyalgia (FM) is a pain condition with associated symptoms
      contributing to distress. The Fibromyalgia Survey Diagnostic Criteria and
      Severity Scale (FSDC) is a patient-administered questionnaire assessing diagnosis
      and symptom severity. Locations of body pain measured by the Widespread Pain
      Index (WPI), and the Symptom Severity scale (SS) measuring fatigue, unrefreshing
      sleep, cognitive and somatic complaints provide a score (0-31), measuring a
      composite of polysymptomatic distress. The reliability and validity of the
      translated French version of the FSDC was evaluated. METHODS: The French FSDC was
      administered twice to 73 FM patients, and was correlated with measures of symptom
      status including: Fibromyalgia Impact Questionnaire (FIQ), Health Assessment
      Questionnaire (HAQ), McGill Pain Questionnaire (MPQ), and a visual analogue scale
      (VAS) for global severity and pain. Test-retest reliability, internal
      consistency, and construct validity were evaluated. RESULTS: Test-retest
      reliability was between .600 and .888 for the 25 single items of the FSDC, and
      .912 for the total FSDC, with all correlations significant (p < 0.0001). There
      was good internal consistency measured by Cronbach's alpha (.846 for FSDC
      assessment 1, and .867 for FSDC assessment 2). Construct validity showed
      significant correlations between the FSDC and FIQ 0.670, HAQ 0.413, MPQ 0.562,
      global VAS 0.591, and pain VAS 0.663 (all p<0.001). CONCLUSIONS: The French FSDC
      is a valid instrument in French FM patients with reliability and construct
      validity. It is easily completed, simple to score, and has the potential to
      become the standard for measurement of polysymptomatic distress in FM.

PMID- 22994976
TI  - Realization of the reversible vesicle-micelle transition of vitamin-derived
      bolaamphiphiles by heat change monitoring.
AB  - The real-time energetics involved in the structural change of a zwitterionic
      vitamin-derived bolaamphiphiles (DDO) vesicles, which were induced by
      conventional surfactants, such as hexadecyltrimethylammonium bromide (CTAB),
      sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), was characterized by
      isothermal titration calorimetry (ITC). Interactions of both CTAB and SDS with
      DDO were accompanied with considerable heat release whereas the interaction
      energetics between TX-100 and the vesicles were small. However, the transition of
      DDO vesicles to micelles did occur upon the addition of all of the three
      surfactants. Fine inflection points were observed in heat flow enthalpograms,
      which indicated systematically the change of vesicle structure. By monitoring the
      interaction of CTAB with DDO, we found that heat release kept constant over a
      certain concentration range at higher temperatures. The repairing effect of
      heating was revealed and a reversible transition from micelles to vesicles of DDO
      was thus realized. Further encapsulation of fluorescein in DDO vesicles proved
      that the reversible vesicle-micelle transition was controllable. This research
      demonstrates that ITC combined with complementary analytical methods such as
      dynamic light scattering (DLS) and transmission electron microscopy (TEM) helps
      to get the real-time information of the structural changes of vesicles. It also
      shows that these synthetic novel bolaamphiphiles offer great promise for
      designing controllable release system.

PMID- 22994977
TI  - A single nucleotide polymorphism in the promoter region of river buffalo stearoyl
      CoA desaturase gene (SCD) is associated with milk yield.
AB  - An association study between the milk yield trait and the stearoyl-CoA desaturase
      (SCD) polymorphism (g.133A > C) in Italian Mediterranean river buffalo was
      carried out. A full characterization of the river buffalo SCD promoter region was
      presented. Genotyping information was provided and a quick method for allelic
      discrimination was developed. The frequency of the C allele was 0.16. Test-day
      (TD) records (43 510) of milk production belonging to 226 lactations of 169
      buffalo cows were analysed with a mixed linear model in order to estimate the
      effect of g.133A > C genotype, as well as the effect of parity and calving
      season. The SCD genotype was significantly associated with milk yield (P = 0.02).
      The genotype AC showed an over-dominance effect with an average daily milk yield
      approximately 2 kg/d higher than CC buffaloes. Such a difference represents about
      28% more milk/d. The effect of the genotype was constant across lactation stages.
      The contribution of SCD genotype (r(2)SCD) to the total phenotypic variance in
      milk yield was equal to 0.12. This report is among the first indications of
      genetic association between a trait of economic importance in river buffalo.
      Although such results need to be confirmed with large-scale studies in the same
      and other buffalo populations, they might offer useful indications for the
      application of MAS programmes in river buffalo and in the future they might be of
      great economic interest for the river buffalo dairy industry.

PMID- 22994974
TI  - Role of tight junction proteins in gastroesophageal reflux disease.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is associated with impaired
      epithelial barrier function that is regulated by cell-cell contacts. The aim of
      the study was to investigate the expression pattern of selected components
      involved in the formation of tight junctions in relation to GERD. METHODS: Eighty
      four patients with GERD-related symptoms with endoscopic signs (erosive: n = 47)
      or without them (non-erosive: n = 37) as well as 26 patients lacking GERD
      specific symptoms as controls were included. Endoscopic and histological
      characterization of esophagitis was performed according to the Los Angeles and
      adapted Ismeil-Beigi criteria, respectively. Mucosal biopsies from distal
      esophagus were taken for analysis by histopathology, immunohistochemistry and
      quantitative reverse-transcription polymerase chain reaction (RT-PCR) of five
      genes encoding tight junction components [Occludin, Claudin-1, -2, Zona occludens
      (ZO-1, -2)]. RESULTS: Histopathology confirmed GERD-specific alterations as
      dilated intercellular spaces in the esophageal mucosa of patients with GERD
      compared to controls (P < 0.05). Claudin-1 and -2 were 2- to 6-fold upregulation
      on transcript (P < 0.01) and in part on protein level (P < 0.015) in GERD, while
      subgroup analysis of revealed this upregulation for ERD only. In both erosive and
      non-erosive reflux disease, expression levels of Occludin and ZO-1,-2 were not
      significantly affected. Notably, the induced expression of both claudins did not
      correlate with histopathological parameters (basal cell hyperplasia, dilated
      intercellular spaces) in patients with GERD. CONCLUSIONS: Taken together, the
      missing correlation between the expression of tight junction-related components
      and histomorphological GERD-specific alterations does not support a major role of
      the five proteins studied in the pathogenesis of GERD.

PMID- 22994978
TI  - Reactive lymphoid follicles with germinal centers in granulomatous mycosis
      fungoides: a case report with review  of the literature.

PMID- 22994979
TI  - Kidney procurement from donors after circulatory death; is there scope for
      improvement?

PMID- 22994980
TI  - Bacterial degradation of risperidone and paliperidone in decomposing blood.
AB  - The stability of two benzisoxazole antipsychotics was determined in vitro in
      decomposing porcine blood inoculated with bacteria, utilizing a high-performance
      liquid chromatography with ultraviolet and fluorescence detection method for drug
      quantitation. Stability experiments for risperidone and paliperidone were
      conducted at 7, 20 and 37 degrees C for 4 days using sterile and bacterially
      inoculated porcine blood. The drugs were stable in sterile blood at each
      temperature and in inoculated blood at 7 degrees C, but degraded significantly in
      inoculated blood at 20 and 37 degrees C. Complete loss occurred within 2 days
      when incubated at 37 degrees C. The benzisoxazole-cleaved degradation products
      for both drugs were identified as 2-hydroxybenzoyl-risperidone and 2
      hydroxybenzoyl-paliperidone utilizing liquid chromatography quadrupole-time-of
      flight mass spectrometry and accurate mass measurements. The degradation products
      have been found in postmortem case studies, including one case where risperidone
      and paliperidone were not detected, indicating complete conversion can occur in
      situ.

PMID- 22994981
TI  - Estimation of skin phototypes with optical parameters: an experimental study
      using newly developed fibre optic detection device.
AB  - In an experimental study (October 2010 Mannheim Germany) with 99 Caucasian
      volunteers, the skin colour (L*, a*, b*) and the reflectance spectra of human
      skin were compared to the Fitzpatrick's sun-reactive skin photo types (SPT). For
      this purpose, the skin colour and the reflectance spectra of human skin were
      determined using non-invasive method with a newly developed fibre optic detection
      device. The device, based on reflectance spectroscopy, was designed and optimized
      using a commercial optical analysis Software. By means of the measured spectra of
      scattered light, the colour values and the absorption spectra of the skin were
      calculated. Neither any of the L*, a*, b* colour values nor any of the parameters
      of the absorbance spectra can be used alone to assess the skin type properly.
      Therefore, an ordinal logistic regression analysis was performed, using the
      statistical computing software r, to correlate the skin types with the measured
      optical parameters. It turned out that the detection device combined with the
      extended statistical analysis gives a better estimate of skin type in respect of
      the measured optical parameters than a procedure with only L*, a*, b* colour
      values. Even with the extended methodology, the procedure gives only a rough
      estimation of the skin type.

PMID- 22994982
TI  - Association between coronary artery disease diagnosed by coronary angiography and
      breast arterial calcifications on mammography: meta-analysis of the data.
AB  - BACKGROUND: Previous studies evaluating breast arterial calcifications (BAC) as a
      risk marker for coronary artery disease (CAD) have been limited by sample size
      and have yielded mixed results. Our objective was to evaluate the association of
      BAC and CAD. METHODS: Data sources included Medline (1970-2010), the Cochrane
      Controlled Trials Register electronic database (1970-2010), and CINAHL (1970
      2010). The search strategy included the keywords, breast artery calcification,
      vascular calcification on mammogram, coronary angiography, and meta-analysis.
      Eligible studies included female patients who had undergone coronary angiography,
      the gold standard for diagnosing CAD, and had screening mammograms that revealed
      the presence or absence of BAC. Information on eligibility criteria, baseline
      characteristics, results, and methodologic quality was extracted by two
      reviewers. Disagreements were resolved by consensus. RESULTS: A total of 927
      patients were enrolled in the five studies. There was a 1.59 (95% confidence
      interval [CI] 1-21-2.09) increased odds of angiographically defined CAD in
      patients with BAC seen on mammography. CONCLUSIONS: The presence of BAC on
      mammography appears to increase the risk of having obstructive CAD on coronary
      angiography; thus, BAC may not be a benign finding.

PMID- 22994983
TI  - High-risk behavior and sexually transmitted infections among U.S. active duty
      servicewomen and veterans.
AB  - The number of women who are active duty service members or veterans of the U.S.
      military is increasing. Studies among young, unmarried, active duty servicewomen
      who are sexually active indicate a high prevalence of risky sexual behaviors,
      including inconsistent condom use, multiple sexual partners, and binge drinking,
      that lead to unintended and unsafe sex. These high-risk sexual practices likely
      contribute to chlamydia infection rates that are higher than the rates in the
      U.S. general population. Human papillomavirus (HPV) infection and cervical
      dysplasia may also be higher among young, active duty servicewomen. Little is
      known about the sexual practices and rates of sexually transmitted infections
      among older servicewomen and women veterans; however, women veterans with a
      history of sexual assault may be at high risk for HPV infection and cervical
      dysplasia. To address the reproductive health needs of military women,
      investigations into the prevalence of unsafe sexual behaviors and consequent
      infection among older servicewomen and women veterans are needed. Direct
      comparison of military and civilian women is needed to determine if servicewomen
      are a truly high-risk group. Additionally, subgroups of military women at
      greatest risk for these adverse reproductive health outcomes need to be
      identified.

PMID- 22994984
TI  - Longer duration of hormonal contraceptive use predicts better cognitive outcomes
      later in life.
AB  - BACKGROUND: The cognitive effects of postmenopausal hormone therapy (HT) have
      been studied extensively, but little is known about the relationship between
      premenopausal hormone use and cognition. Hormonal contraceptive use vs. nonuse
      may be a potential factor influencing cognitive processes in midlife. The aim of
      this study is to explore the effect of modification of hormone milieu through use
      of hormonal contraception in premenopausal women and midlife cognitive function.
      METHODS: Subjects were 261 cognitively normal women, aged 40-65 (mean MU=52),
      enrolled in the Wisconsin Registry for Alzheimer's Prevention. All women
      completed the Women's Health History Questionnaire and a self-report health
      history questionnaire and were administered a battery of neuropsychologic tests.
      Cognitive results were analyzed using summary scores for the domains of Verbal
      Ability, Visuo-spatial Ability, Working Memory, Verbal Learning & Memory, and
      Speed & Flexibility derived using a confirmatory factor analysis. RESULTS:
      Hormonal contraceptive ever users performed significantly better than never users
      in the domains of Visuo-spatial Ability (MU=0.75, 95% confidence interval [CI]
      0.23-1.28, p=0.005) and Speed & Flexibility (MU=0.52, 95% CI -0.16-1.04,
      p=0.007), with duration-dependent increases in performance, especially in ever
      users with >= 15 years of use. CONCLUSIONS: These data provide preliminary
      evidence that hormonal contraceptive use may influence cognitive outcomes, even
      years after use is discontinued. Hormonal contraceptive users scored better in
      domains of Visuo-spatial Ability and Speed & Flexibility than never users, with a
      duration-dependent trend. Further research is needed to explore the use of
      hormonal contraceptives to prevent or delay cognitive decline and to clarify the
      physiologic basis of this phenomenon.

PMID- 22994985
TI  - Now what? Effects of on-site assessment on treatment entry after perinatal
      depression screening.
AB  - BACKGROUND: Depression is a frequent accompaniment of the perinatal period.
      Although screening improves detection of perinatal depression, it does not in
      itself improve mental health treatment entry and, therefore, does not improve
      outcomes. This study addresses the feasibility of incorporating diagnostic
      assessment for depression directly into perinatal care visits and the influence
      of doing so on entry into mental health treatment. METHODS: The Perinatal
      Depression Management Program was implemented in an urban community health center
      serving a predominantly Hispanic population. The Patient Health Questionnaire
      (PHQ-9) was administered during perinatal visits. Positive screens (scores >=10)
      were followed within the same visit by brief diagnostic assessment and engagement
      strategies. Chart review was conducted to compare rates of screening, assessment,
      and treatment entry during a 3-month baseline period before implementation of the
      intervention (n=141) with a 1-year period after implementation of the
      intervention (n=400). RESULTS: Before the intervention, 65.2% of patients
      completed a PHQ-9, and 10% of patients with positive screens received on-site
      assessment. None of the patients with identified perinatal depression entered
      treatment. After model implementation, significantly more (93.5%) completed a PHQ
      9, and of patients with positive screens, 84.8% received an on-site assessment.
      Among patients diagnosed with major depression and offered treatment, 90% entered
      treatment. CONCLUSIONS: It is feasible to implement diagnostic assessment for
      depression within perinatal clinic visits. Doing so may substantially increase
      entry into mental health treatment for women with perinatal major depression
      while reducing unnecessary mental health referral of patients with false positive
      screens.

PMID- 22994987
TI  - Reason and value: making reasoning fit for practice.

PMID- 22994988
TI  - Critical thinking in clinical medicine: what is it?
AB  - In this paper, we explore the recent emphasis, in various medical contexts, of
      the term 'critical' or the notion of 'being critical'. We identify various
      definitions of being critical and note that they differ strikingly. What are
      these different uses of the term trying to capture that is important in clinical
      medicine and medical education? We have analysed these qualities as
      responsibilist, epistemic virtues. We believe that a virtues approach is best
      able to make sense of the non-cognitive elements of 'being critical', such as the
      honesty and courage to question claims in the face of persuasion, authority or
      social pressure. Medical educators and professional bodies seem to agree that
      being critical is important and desirable. Yet, it is unclear how this quality
      can be optimally fostered and balanced with the constraints that act upon
      individual practitioners in the context of institutional medicine including
      professional standards and the demands of the doctor-patient relationship. Other
      constraints such as authoritarianism, intimidation and financial pressures may
      act against the expression of being critical or even the cultivation of critical
      thinking. The issue of the constraints on critical thinking and the potential
      hazards it entails will require further consideration by those who encourage
      being critical in medicine.

PMID- 22994986
TI  - Best practices and pearls in interdisciplinary mentoring from Building
      Interdisciplinary Research Careers in Women's Health Directors.
AB  - BACKGROUND: Increasingly, national programs and leaders are looking at
      interdisciplinary collaborations as essential to future research. Twelve years
      ago, the National Institutes of Health (NIH) Office of Research on Women's Health
      (ORWH) developed and implemented the Building Interdisciplinary Research Careers
      in Women's Health (BIRCWH) K12 program to focus on interdisciplinary mentored
      career development for junior faculty in women's health research. METHODS: We
      applied a mixed-methods approach using an electronic survey and in-person
      presentations and discussions to understand best practices and lessons learned
      for interdisciplinary mentoring across BIRCWH K12 program leaders. RESULTS AND
      CONCLUSIONS: We received responses from all 29 active BIRCWH programs. Factors
      associated with success included ensuring sufficient protected time for regular
      (weekly or biweekly) mentoring; mentors promoting the research independence of
      the Scholar; a team mentoring approach, including career as well as content
      mentors; and explicit and clear expectations outlined between the Scholar and
      mentor. The majority of programs conduct formal evaluations of mentorship, and
      79% of programs offer training in mentorship for either Scholars, mentors, or
      both. This article presents program leaders' best practices, challenges, and
      lessons learned from mentoring junior faculty who are conducting women's health
      research, whether basic, clinical, behavioral, translational, or health services
      research, using an interdisciplinary mentoring approach.

PMID- 22994989
TI  - Conciliating cognition and consciousness: the perceptual foundations of clinical
      reasoning.
AB  - Clinical reasoning has been defined as a form of cognition applied to evaluating
      and managing a patient's medical problem. As a kind of cognition, a product of
      the human psyche, it is logical to expect that clinical reasoning should be best
      understood through methods derived from psychology, neuropsychology and the
      cognitive sciences. However, the application of scientific methods to evaluating
      clinical reasoning is unable to analyse clinical reasoning in terms of first
      person experience and consciousness. By reducing clinical reasoning to its
      cognitive components the cognitivist approach tends to ignore the larger context
      in which clinical reasoning occurs. By reducing its conception of clinical
      reasoning to its cognitive components, the neuropsychological approach fails to
      acknowledge clinical reasoning as a form of intentionality, a gestalt, grounded
      in human perception. A full epistemology of clinical reasoning requires a
      phenomenological analysis that can make sense of the relation between pre
      reflective consciousness and explicit forms of knowing. In this paper I
      conciliate cognition and consciousness in medicine through analysing the
      phenomenology of perception in clinical reasoning. I compare the application of
      phenomenology to clinical reasoning with the attempt to model clinical reasoning
      on Aristotelian practical wisdom or phronesis. Finally, I analyse empathy as a
      type of perception critical for effective clinical interaction and exemplary for
      reflecting on perception as the intersubjective foundation of clinical reasoning.

PMID- 22994990
TI  - What is knowledge and when should it be implemented?
AB  - A primary purpose of research is to generate new knowledge. Scientific advances
      have progressively identified optimal ways to achieve this purpose. Included in
      this evolution are the notions of evidence-based medicine, decision aids, shared
      decision making, measurement and evaluation as well as implementation. The
      importance of including qualitative and quantitative methods in our research is
      now understood. We have debated the meaning of evidence and how to implement it.
      However, we have yet to consider how to include in our study findings other types
      of information such as tacit and experiential knowledge. This key consideration
      needs to take place before we translate new findings or 'knowledge' into clinical
      practice. This article critiques assumptions regarding the nature of knowledge
      and suggests a framework for implementing research findings into practice.

PMID- 22994991
TI  - An integrated model of clinical reasoning: dual-process theory of cognition and
      metacognition.
AB  - RATIONALE AND AIM: Clinical reasoning is an important component for providing
      quality medical care. The aim of the present paper is to develop a model of
      clinical reasoning that integrates both the non-analytic and analytic processes
      of cognition, along with metacognition. METHOD: The dual-process theory of
      cognition (system 1 non-analytic and system 2 analytic processes) and the
      metacognition theory are used to develop an integrated model of clinical
      reasoning. RESULTS: In the proposed model, clinical reasoning begins with system
      1 processes in which the clinician assesses a patient's presenting symptoms, as
      well as other clinical evidence, to arrive at a differential diagnosis.
      Additional clinical evidence, if necessary, is acquired and analysed utilizing
      system 2 processes to assess the differential diagnosis, until a clinical
      decision is made diagnosing the patient's illness and then how best to proceed
      therapeutically. Importantly, the outcome of these processes feeds back, in terms
      of metacognition's monitoring function, either to reinforce or to alter cognitive
      processes, which, in turn, enhances synergistically the clinician's ability to
      reason quickly and accurately in future consultations. CONCLUSIONS: The proposed
      integrated model has distinct advantages over other models proposed in the
      literature for explicating clinical reasoning. Moreover, it has important
      implications for addressing the paradoxical relationship between experience and
      expertise, as well as for designing a curriculum to teach clinical reasoning
      skills.

PMID- 22994992
TI  - Compellingness: assessing the practical relevance of clinical research results.
AB  - While the critical appraisal of clinical research has generally focused on
      aspects of study design and statistical analysis, other features of clinical
      studies appear to be more important to clinicians for assessing the value of a
      particular study in the care of particular patients. These features relate to the
      quality of the knowledge derived from the research, the value of the results to
      the care of individual patients, and the responsibility of clinicians to be
      stewards of limited resources. Twelve features of clinical research studies that
      affect how compelling individual clinicians find the results are proposed and
      examined here. By better understanding what makes clinical research compelling
      enough to alter or reinforce clinical practice, clinical researchers can design
      future studies to better serve the needs of clinicians and patients.

PMID- 22994993
TI  - Principles of reasoning in historical epidemiology.
AB  - The case of John Snow has long been important to epidemiologists and public
      health officials. However, despite the fact that there have been many discussions
      about the various aspects of Snow's case, there has been virtually no discussion
      about what guided Snow's reasoning in his coming to believe his various
      conclusions about cholera. Here, I want to take up this question in some detail
      and show that there are a number of specific principles of reasoning that played
      a crucial role for Snow. Moreover, these principles were epistemologically
      important to Snow, a fact about which Snow is explicit in many places. An
      analysis of Snow's case suggests that, because of the epistemic role such
      principles of reasoning can play, health care practitioners ought to understand
      their practices to be theoretically informed in these ways, and not just data
      driven.

PMID- 22994994
TI  - Many-models medicine: diversity as the best medicine.
AB  - Many medicines have been proposed to cure various ills of biomedicine including
      evidence-based medicine, evolutionary medicine, narrative medicine, and
      complexity medicine, among others. To the extent that all models are
      idealizations or abstractions, all of these model medicines are imperfect in some
      respects. In the absence of a single unified model, if indeed unification is
      possible or even desirable, and despite the relative advantages of one model or
      another, in practice many models and methods are necessary in medicine. In this
      article, I consider the value of such diversity in models and methods. I briefly
      describe several models. Then I discuss simulations of agents who use diverse
      models. Advocates of models such as those discussed here typically claim that we
      should use their preferred model because it is the best. Evidence-based medicine,
      for instance, has been promoted as the single best model of medicine while other
      models have been cast as lesser models or in opposition to it and each other. But
      isolated models and methods may never be as good as groups of models and methods.
      Debates about various individual models may result in better outcomes, but
      explicitly choosing to use many models is likely to produce even better outcomes.

PMID- 22994995
TI  - How does a psychiatrist infer from an observed condition to a case of mental
      disorder?
AB  - The main thesis of this paper is that mental health practitioners can
      legitimately infer that a patient's given condition is a case of mental disorder
      without having diagnosed any specific mental disorder. The article shows how this
      is justifiable by relying either on psychopathological reasoning, on
      'intentional' analysis or possibly on other modes of reasoning. In the end, it
      highlights the clinical and philosophical consequences of the plurality of modes
      of 'inferences to mental disorder'.

PMID- 22994996
TI  - Challenging the epistemological foundations of EBM: what kind of knowledge does
      clinical practice require?
AB  - This paper raises questions about the epistemological foundations of evidence
      based medicine (EBM). We argue that EBM is based upon reliabilist epistemological
      assumptions, and that this is appropriate - we should focus on identifying the
      most reliable processes for generating and collecting medical knowledge. However,
      we note that this should not be reduced to narrow questions about which research
      methodologies are the best for gathering evidence. Reliable processes for
      generating medical evidence might lie outside of formal research methods. We also
      question the notion of the knower that is assumed by EBM. We argue that EBM
      assumes an enlightenment conception of knowers as autonomous, substitutable
      individuals. This conception is troubled by the way that clinicians learn the
      role of anecdote in health care and the role of patient choice, all of which
      bring into play features of clinicians and patients as situated individuals with
      particular backgrounds and experiences. EBM's enlightenment conception of the
      knower is also troubled by aspects of the way evidence is produced. Given these
      limitations, we argue that EBM should retain its reliabilist bent, but should
      look beyond formal research methodologies in identifying processes that yield
      reliable evidence for clinical practice. We suggest looking to feminist
      epistemology, with its focus on the standpoints of individual situated knowers,
      and the role of social context in determining what counts as knowledge.

PMID- 22994997
TI  - Mechanisms: what are they evidence for in evidence-based medicine?
AB  - Even though the evidence-based medicine (EBM) movement labels mechanisms a low
      quality form of evidence, consideration of the mechanisms on which medicine
      relies, and the distinct roles that mechanisms might play in clinical practice,
      offers a number of insights into EBM itself. In this paper, I examine the
      connections between EBM and mechanisms from several angles. I diagnose what went
      wrong in two examples where mechanistic reasoning failed to generate accurate
      predictions for how a dysfunctional mechanism would respond to intervention. I
      then use these examples to explain why we should expect this kind of mechanistic
      reasoning to fail in systematic ways, by situating these failures in terms of
      evolved complexity of the causal system(s) in question. I argue that there is
      still a different role in which mechanisms continue to figure as evidence in EBM:
      namely, in guiding the application of population-level recommendations to
      individual patients. Thus, even though the evidence-based movement rejects one
      role in which mechanistic reasoning serves as evidence, there are other
      evidentiary roles for mechanistic reasoning. This renders plausible the claims of
      some critics of EBM who point to the ineliminable role of clinical experience.
      Clearly specifying the ways in which mechanisms and mechanistic reasoning can be
      involved in clinical practice frames the discussion about EBM and clinical
      experience in more fruitful terms.

PMID- 22994998
TI  - Mechanistic understanding in clinical practice: complementing evidence-based
      medicine with personalized medicine.
AB  - In the last century, medicine has undergone an unprecedented wave of radical
      changes. From the implementation of surgery up to the development of single gene
      targeted therapies, clinical decision making has become increasingly complex to
      handle. Today, this complexity needs to be rethought in the light of two emerging
      paradigms: evidence-based medicine (EBM) and personalized medicine (P-Med). The
      new availability of diverse sources of scientific evidence raises significant
      issues concerning how clinicians will compare, evaluate and orient their
      decisions in front of a rapidly growing plethora of therapies, procedures,
      medical technologies and drugs. In this paper, we compare the background visions
      behind these two paradigms, evaluating their respective relevance for present and
      future clinical decision making. In particular, we argue that EBM and P-Med are
      driven by two diverse modes of reasoning about 'evidence making' in medicine. EBM
      is grounded on statistical notions and epidemiological data, generally gathered
      through systematic meta-reviews of randomized controlled trials; P-Med, instead,
      is grounded on mechanistic explanations of molecular interactions, metabolic
      pathways and biomarkers. While both paradigms are epistemically sound, we argue
      that they cannot, and should not, be hybridized into a unique model. Rather, they
      ought to represent two compatible, but alternative ways of informing the clinical
      practice. Hence, we conclude that clinicians may expect to see their
      responsibility increasing as they will deal with diverse, but equally compelling,
      ways of reasoning and deciding about which intervention will qualify as the 'best
      one' in each individual case.

PMID- 22994999
TI  - Causation and evidence-based practice: an ontological review.
AB  - This paper explores the nature of causation within the framework of evidence
      based practice (EBP) for health care. The aims of the paper were first to define
      and evaluate how causation is presently accounted for in EBP; second, to present
      an alternative causal account by which health care can develop in both its
      clinical application and its scientific research activity. The paper was premised
      on the idea that causation underlies medical and health care practices and
      impacts on the way we understand health science research and daily clinical
      practice. The question of what causation is should therefore be of utmost
      relevance for all concerned with the science, philosophy and progress of EBP. We
      propose that the way causation is thought of in contemporaneous health care is
      exposed by evidential frameworks, which categorize research methods on their
      epistemological strengths. It is then suggested that the current account of
      causation is limited in respect of both the functionality of EBP, and its
      inherent scientific processes. An alternative ontology of causation is provided,
      which has its roots in dispositionalism. Here, causes are not seen as regular
      events necessitating an effect, but rather phenomena that are highly complex,
      context-sensitive and that tend towards an effect. We see this as a better
      account of causation for evidence-based health care.

PMID- 22995000
TI  - The application of Cartwright's concept of capacities to complex interventions in
      psychiatry.
AB  - Cartwright and Munro argued that extrapolation of findings from randomized
      controlled trials to other settings can be difficult because information about
      the underlying causal structure and subgroups is often not available. They
      advocated the use of 'capacities' - that is fixed causal contributions - in
      predicting effects of interventions. In psychiatry, it is often not possible to
      determine what the fixed causal contributions are and one can only establish
      'approximate capacities'. However, using 'approximate capacities' does imply a
      different way of evaluating health services, especially combined interventions.
      In health service research, if different studies, randomized controlled trials or
      other designs, have given different outcomes, the best way to investigate the
      effectiveness of a particular way of service organization is not to conduct more
      randomized controlled trials. It is preferable to study the effects of certain
      elements of the complex intervention, which have been tested before in other
      settings, that is investigating 'approximate capacities'. One should check
      whether the separate elements do form a part of the complex intervention in
      practice and whether they have the same effect as in other studies and if not,
      why not. This enhances knowledge about the underlying causal structure and
      increases the possibility of extrapolation of the findings.

PMID- 22995001
TI  - Capacities in psychiatry: a commentary on Hubbeling.

PMID- 22995002
TI  - Values-based medicine and modest foundationalism.
AB  - Philosophically, values refer to the basic commitments that justify judgements,
      beliefs and practices, both at the community and personal levels. The study of
      these kinds of values is axiology. We suggest that all people subscribe to three
      foundational values - survival, security and flourishing - and that these
      foundational values are expressed by way of concepts, systems, principles and
      practices that may differ substantially from culture to culture. Values can stand
      on their own as foundational justifications for health care and medicine. Many
      ethical quandaries can be better understood, even though they may remain
      unsolved, by reference to the foundational values that people can agree upon.
      This version of values-based health care has strong claims to prior logical
      status as a justification for the whole enterprise of health care, and values
      based medicine is a part of this larger domain.

PMID- 22995003
TI  - Meaning and value in medical school curricula.
AB  - RATIONALE, AIMS AND OBJECTIVES: Bioethics and professionalism are standard
      subjects in medical training programmes, and these curricula reflect particular
      representations of meaning and practice. It is important that these curricula
      cohere with the actual concerns of practicing clinicians so that students are
      prepared for real-world practice. We aimed to identify ethical and professional
      concerns that do not appear to be adequately addressed in standard curricula by
      comparing ethics curricula with themes that emerged from a qualitative study of
      medical practitioners. METHOD: Curriculum analysis: Thirty-two prominent ethics
      and professionalism curricula were identified through a database search and were
      analysed thematically. Qualitative study: In-depth, semi-structured interviews
      were conducted with 20 medical practitioners. Participants were invited to
      reflect upon their perceptions of the ways in which values matter in their
      practices and their educational experiences. The themes emerging from the two
      studies were compared and contrasted. RESULTS: While representations of meaning
      and value in ethics and professionalism curricula overlap with the preoccupations
      of practicing clinicians, there are significant aspects of 'real-world' clinical
      practice that are largely ignored. These fell into two broad domains: (1)
      'sociological' concerns about enculturation, bureaucracy, intra-professional
      relationships, and public perceptions of medicine; and (2) epistemic concerns
      about making good decisions, balancing different kinds of knowledge, and
      practising within the bounds of professional protocols. CONCLUSIONS: Our findings
      support the view that philosophy and sociology should be included in medical
      school and specialty training curricula. Curricula should be reframed to
      introduce students to habits of thought that recognize the need for critical
      reflection on the social processes in which they are embedded, and on the
      philosophical assumptions that underpin their practice.

PMID- 22995004
TI  - Ethics between curriculum and workplace.

PMID- 22995006
TI  - Autonomy and reason: treatment choice in breast cancer.
AB  - The practice of offering choice to those women with breast cancer for whom either
      breast conserving surgery or mastectomy would be equally beneficial has come to
      be seen as an important aspect of medical care. As well as improving satisfaction
      with treatment, this is seen as satisfying the ethical principle of respect for
      autonomy. A number of studies, however, show that women are not always
      comfortable with such choice, preferring to leave treatment decisions to their
      surgeons. A question then arises as to the extent that these women can be seen as
      autonomous or as exercising autonomy. This paper argues, however, that the
      understanding of autonomy which is applied in current approaches to breast cancer
      care does not adequately support the exercise of autonomy, and that the clinical
      context of care means that women are not able to engage in the kind of reasoning
      that might promote the exercise of autonomy. Where respect for autonomy is
      limited to informed consent and choice, there is a danger that women's interests
      are overlooked in those aspects of their care where choice is not appropriate,
      with very real, long-term consequences for some women. Promoting the exercise of
      autonomy, it is argued, needs to go beyond the conception of autonomy as rational
      individuals making their own decisions, and clinicians need to work with an
      understanding of autonomy as relational in order to better involve women in their
      care.

PMID- 22995005
TI  - Unreasonable reasons: normative judgements in the assessment of mental capacity.
AB  - The recent Mental Capacity Act (2005) sets out a test for assessing a person's
      capacity to make treatment choices. In some cases, particularly in psychiatry, it
      is unclear how the criteria ought to be interpreted and applied by clinicians. In
      this paper, I argue that this uncertainty arises because the concept of capacity
      employed in the Act, and the diagnostic tools developed to assist its assessment,
      overlook the inherent normativity of judgements made about whether a person is
      using or weighing information in the decision-making process. Patients may fail
      on this criterion to the extent that they do not appear to be handling the
      information given in an appropriate way, on account of a mental impairment
      disrupting the way the decision process ought to proceed. Using case law and
      clinical examples, I describe some of the normative dimensions along which
      judgements of incapacity can be made, namely epistemic, evaluative and affective
      dimensions. Such judgements are complex and the normative standards by which a
      clinician may determine capacity cannot be reduced to a set of criteria. Rather,
      in recognizing this normativity, clinicians may better understand how clinical
      judgements are structured and what kinds of assumption may inform their
      assessment.

PMID- 22995007
TI  - Imperfection, practice and humility in clinical ethics.
AB  - In this essay, I provide a description of the discipline of ethics using the
      philosophies of Aristotle and the American pragmatist John Dewey. Specifically, I
      argue that ethics is an active undertaking that is ambiguous and pluralistic. I
      then normatively prescribe the way in which clinical ethicists ought to approach
      their work in medicine. Rather than endeavouring to become, or behaving as if
      they are, experts, clinical ethicists must be humble. They must practise ethics.
      That is, they must admit ethics is the study and pursuit of the good life but
      that this study and pursuit occurs imperfectly in the face of problematic
      situations.

PMID- 22995008
TI  - Interdisciplinary workshop report: methodology and 'Personhood and Identity in
      Medicine'.

PMID- 22995009
TI  - The narrative sense of self.

PMID- 22995010
TI  - Narrative identity and illness.

PMID- 22995011
TI  - Interdisciplinary workshop in the philosophy of medicine: death.

PMID- 22995012
TI  - Living, dying and the nature of death.

PMID- 22995013
TI  - Can there be a good death?
AB  - While some deaths are worse than others, there is no such thing as a 'good death'
      since the plausible desiderata of a 'good death' form an inconsistent set.
      Because death is of the greatest existential consequence to us, a 'good' death
      must be a self-aware death in which we grasp the import of what is happening to
      us; however, such realization is incompatible with our achieving the tranquillity
      of mind which is another requirement for the 'good' death. Nevertheless, the
      welcome recognition in recent years by medical personnel, palliative care workers
      and hospice staff that dying is an existential predicament as well as a
      physiological condition has enabled more people to avoid a 'soulless death in
      intensive care', even if it pays insufficient regard to the personal virtues that
      we need if we are to mitigate the worst evils of dying.

PMID- 22995014
TI  - Bernard Williams on living long and living well.

PMID- 22995015
TI  - Can we be harmed after we are dead?

PMID- 22995016
TI  - The lived body as a medical topic: an argument for an ethically informed
      epistemology.

PMID- 22995017
TI  - Medicine and the individual: is phenomenology the answer?
AB  - The issue of how to incorporate the individual's first-hand experience of illness
      into broader medical understanding is a major question in medical theory and
      practice. In a philosophical context, phenomenology, with its emphasis on the
      subject's perception of phenomena as the basis for knowledge and its questioning
      of naturalism, seems an obvious candidate for addressing these issues. This is a
      review of current phenomenological approaches to medicine, looking at what has
      motivated this philosophical approach, the main problems it faces and suggesting
      how it might become a useful philosophical tool within medicine, with its own
      individual, but interrelated, contribution to make to current medical debates.
      After the general background, there is a brief summary of phenomenological ideas
      and their current usage in a medical context. Next is a critique of four key
      claims within current phenomenological medical works, concerning both the role
      phenomenology plays and the supposedly clear divide between phenomenology and
      other approaches. There are significant problems within these claims, largely
      because they overlook the complexity of the questions they consider. Finally,
      there is some more in-depth examination of phenomenology itself and the true
      complexity of phenomenological debate concerning subjectivity. The aim is to show
      that it will be both more productive and truer to phenomenology itself, if we use
      phenomenology as a philosophical method for explicating and gaining deeper
      understanding of complex and fundamental problems, which are central to medicine,
      rather than as providing simple, but flawed solutions.

PMID- 22995018
TI  - Commentary on Gupta, Mona (2011): improved health or improved decision making?
      The ethical goals of EBM. Journal of Evaluation in Clinical Practice 17(5), 957
      963.

PMID- 22995019
TI  - Evidence-based medicine: we ought to practise it, but we still do not know why.

PMID- 22995020
TI  - Family- and school-based predictors of energy balance-related behaviours in
      children: a 6-year longitudinal study.
AB  - OBJECTIVE: To examine family- and school-based predictors of breakfast
      consumption, soft drink consumption and physical activity (PA) and moderating
      effects of gender and socio-economic status (SES). DESIGN: Longitudinal study (6
      year follow-up), including a questionnaire about dietary and activity behaviour.
      SETTING: Fifty-nine Flemish elementary schools. SUBJECTS: Seven hundred and
      twenty-seven children (51.9 % girls, 51.9 % high SES, mean age 9.9 (sd 0.4) years
      at baseline). RESULTS: Having breakfast together with parents (P < 0.001) at age
      10 years related to more days of eating breakfast at age 16 years. More parental
      soft drink consumption (P = 0.04), less soft drink availability at home (P <
      0.001) and less parental permissiveness (children received soft drinks from their
      parents whenever they asked for it and children could take soft drinks whenever
      they wanted; P = 0.02 and P = 0.001, respectively) at age 10 years related to
      less soft drink consumption at age 16 years. A more positive parental attitude
      towards PA (P = 0.009), more parental encouragement (P = 0.002) and a higher
      rating of PA's benefit 'relaxing' (P < 0.001) at age 10 years related to more PA
      at age 16 years. Gender and SES did not significantly moderate any of the
      associations. CONCLUSIONS: Only parental factors at age 10 years were associated
      with breakfast consumption, soft drink consumption and PA at age 16 years. An
      intervention programme at age 10 years with a strong focus on the modifiable
      parental factors might lead to healthy behaviour in the long term.

PMID- 22995021
TI  - Older people's exclusion from healthcare services in Nepal: an analysis of the
      political economy of development aid, domestic policy and research.
AB  - The objective of this review was to contribute to the discussion on older
      people's access to healthcare in developing countries. Relevant research
      findings, survey reports, policy papers and planning documents were critically
      reviewed, placing a particular focus on their relevance in understanding issues
      of access, equity and justice. A number of factors are identified for their roles
      on the issue; that is, place of residence, economic factors/poverty, cultural
      stigma, situation and impact of research, and the prevalent policy framework in
      health and the approach of development assistance adopted by donor communities.
      In order to make healthcare facilities equitable for older people, the identified
      factors need to be addressed at different levels - at local policy work, in the
      allocation of funding for health service research and in designing overseas
      development work.

PMID- 22995022
TI  - Valve prosthesis-patient mismatch (VP-PM): a long-term perspective.
AB  - The concept/phenomenon of valve prosthesis/patient mismatch (VP-PM), described in
      1978, has stood the test of time. From that time to 2011, VP-PM has received a
      great deal of attention but studies have come to varying conclusions. This is
      largely because of the determination of prosthetic heart valve area [called
      effective orifice area index (EOAi)] by projection rather than by actual
      measurement, variable criteria to assess severity of EOAi and the timing of
      determination of EOAi. All prosthetic heart valves have some degree of VP-PM
      which must be placed in a proper clinical perspective. This can be done by
      determining its effects on function and outcomes. For mortality one needs to
      focus especially on severe/critical degree of VP-PM and determine the cause of
      death was due to VP-PM. For the period "beyond 2011" a road map is suggested that
      will have uniformity of assessment of VP-PM and a focusing on the important goals
      of VP-PM.

PMID- 22995023
TI  - Valve prosthesis-patient mismatch, 1978 to 2011: from original concept to
      compelling evidence.

PMID- 22995024
TI  - Do changes of 6-minute walk distance predict clinical events in patients with
      pulmonary arterial hypertension? A meta-analysis of 22 randomized trials.
AB  - OBJECTIVES: The objectives of this study were to verify whether improvement in 6
      min walk distance (6MWD) is associated with clinical outcome in pulmonary
      arterial hypertension (PAH). BACKGROUND: 6MWD is used as an endpoint to assess
      the benefit of therapies in PAH. However, whether changes in 6MWD correlate with
      clinical outcome is unknown. METHODS: Randomized trials assessing 6MWD in
      patients with PAH and reporting clinical endpoints were included in a meta
      analysis. The meta-analysis was performed to assess the influence of treatment on
      outcomes. Meta-regression analysis was performed to test the relationship between
      6MWD changes and outcomes. RESULTS: Twenty-two trials enrolling 3,112
      participants were included. Active treatments led to significant reduction of all
      cause death (odds ratio [OR]: 0.429; 95% confidence interval [CI]: 0.277 to
      0.664; p < 0.01), hospitalization for PAH, and/or lung or heart-lung
      transplantation (OR: 0.442; 95% CI: 0.309 to 0.632; p < 0.01), initiation of PAH
      rescue therapy (OR: 0.555; 95% CI: 0.347 to 0.889; p = 0.01), and composite
      outcome (OR: 0.400; 95% CI: 0.313 to 0.510; p < 0.01). No relationship between
      6MWD changes and outcomes was detected. CONCLUSIONS: In patients with PAH,
      improvement in 6MWD does not reflect benefit in clinical outcomes.

PMID- 22995025
TI  - The 6-minute walk test as a primary endpoint in clinical trials for pulmonary
      hypertension.

PMID- 22995026
TI  - Cavernous hemangioma of the right atrium: a very rare case of complete
      atrioventricular block.

PMID- 22995027
TI  - Biventricular pacing-induced torsade de pointes.

PMID- 22995028
TI  - Two-year results of reduced-fluence photodynamic therapy for polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To report the results of a 2-year follow-up study of Japanese polypoidal
      choroidal vasculopathy (PCV) patients treated with reduced-fluence photodynamic
      therapy (PDT) monotherapy. DESIGN: Prospective interventional case series.
      METHODS: In the present study, 38 eyes of 38 consecutive patients underwent PDT
      with a reduced laser fluence of 25 J/cm(2). During the 2-year follow-up, visual
      acuity (VA) and optical coherence tomography measurements were performed every 3
      months after the PDT procedure and then compared with baseline values. PCV
      vascular lesions were evaluated by indocyanine green and fluorescein angiography.
      RESULTS: At baseline, the mean logarithm of the minimal angle of resolution
      (logMAR) best-corrected VA (BCVA) was 0.43. There was a significant improvement
      of the mean logMAR BCVA to 0.28 and 0.29 at 12 and 24 months, respectively (P <
      .0001, P = .001). The logMAR BCVA was stable or improved by >=0.3 in 36 (95%) of
      the eyes at the 2-year follow-up. In 13 eyes in which the baseline VA was better
      than 20/40, there was a significant improvement of the mean logMAR BCVA at 12
      months, with the acuities continuing to be stable at 24 months. The mean number
      of treatment sessions during the 24-month study period was 1.9. CONCLUSIONS:
      Reduced-fluence PDT monotherapy for PCV effectively improved and maintained the
      VA over a 24-month period, even in eyes with a baseline VA better than 20/40. In
      addition, the number of treatments could be much smaller as compared with
      intravitreal injection of anti-vascular endothelial growth factor agents.

PMID- 22995029
TI  - Intravitreal triamcinolone versus intravitreal bevacizumab in the treatment of
      exudative retinal detachment secondary to posterior uveal melanoma.
AB  - PURPOSE: To evaluate the efficacy and safety of prompt intravitreal triamcinolone
      acetonide injection (4 mg/0.1 mL) vs intravitreal bevacizumab injection (1.25
      mg/0.05 mL) compared with observation in the management of extensive exudative
      retinal detachment secondary to posterior uveal melanoma. DESIGN: Retrospective,
      nonrandomized, interventional case series. METHODS: setting: Institutional.
      patients: Ninety-six patients affected by posterior uveal melanoma with large
      exudative retinal detachment (>10 mm in largest basal diameter) were included.
      intervention: Patients received intravitreal triamcinolone acetonide (32 eyes) or
      intravitreal bevacizumab (32 eyes) at plaque removal. Thirty-two patients served
      as controls (observation group). All groups were matched for age, sex, initial
      tumor thickness and largest basal diameter, largest exudative retinal detachment
      basal diameter, tumor location, and Bruch membrane rupture. Patients underwent
      monthly follow-up examinations in the first 6 months and every 3 months
      thereafter. Follow-up was longer than 24 months. main outcome measure: Exudative
      retinal detachment resolution (B-scan ultrasonography), steroid-induced cataract,
      steroid-induced increased IOP. RESULTS: Follow-up was 37 +/- 7 months. Marked
      exudative retinal detachment regression was documented in 22 (69%) intravitreal
      triamcinolone acetonide-treated vs 11 (34%) intravitreal bevacizumab-treated and
      9 (28%) untreated eyes (P = .0007 and P = .0001, respectively). No statistical
      significance was found between intravitreal bevacizumab group vs observation
      group (P = .45) Steroid-induced cataract was observed in 4 intravitreal
      triamcinolone acetonide-treated patients (12%). Neither steroid-induced increased
      IOP nor other short- or long-term side effects were documented. CONCLUSION:
      Intraoperative intravitreal triamcinolone acetonide injection induces earlier and
      marked exudative retinal detachment resolution after brachytherapy of posterior
      uveal melanoma. Risk and benefit should be balanced vs steroid-induced cataract.

PMID- 22995030
TI  - Ocular flora and their antibiotic resistance patterns in the midwest: a
      prospective study of patients undergoing cataract surgery.
AB  - PURPOSE: To determine the spectrum of conjunctival flora and the antibiotic
      susceptibility profiles of patients undergoing cataract surgery at a Midwestern
      university. DESIGN: Prospective in vitro laboratory investigation of a patient
      cohort. METHODS: Conjunctival cultures were obtained from patients undergoing
      cataract surgery at a single ambulatory center on the day of surgery before the
      instillation of any ophthalmic medications. Isolates and antibiotic
      susceptibility profiles were identified using standard microbiological
      techniques. RESULTS: A total of 183 eyes were cultured, yielding 225 isolates.
      Twenty-seven eyes (14.8%) showed no growth. Coagulase-negative staphylococci
      (CNS) were the most commonly isolated organisms (74.8%). Overall susceptibility
      was highest for gentamicin (94%), which was also true of the CNS isolates
      (95.0%). A total of 64.5% of CNS isolates were sensitive to ciprofloxacin; 30.1%
      of CNS isolates were resistant to >=3 classes of antibiotics; 46.6% of CNS
      isolates were oxacillin-resistant, and they were more resistant to antibiotics
      than their oxacillin-sensitive counterparts (P < .001), including
      fluoroquinolones (P < .001). Among eyes with multiple CNS strains, 41.4% had
      different antibiotic susceptibility profiles even though they were the same
      species. CONCLUSIONS: Our cohort harbored organisms with similar rates of
      antibiotic resistance as elsewhere in the country, including oxacillin
      resistance; however, the rate of fluoroquinolone resistance was less than in
      other reports. A surprisingly large proportion of different CNS strains from the
      same eye harbored different antibiotic susceptibility profiles. Our in vitro
      results, along with those of other investigators, should prompt further dialogue
      regarding antibiotic of choice for perioperative surgical prophylaxis in
      ophthalmic surgery.

PMID- 22995031
TI  - Open structure ZnO/CdSe core/shell nanoneedle arrays for solar cells.
AB  - Open structure ZnO/CdSe core/shell nanoneedle arrays were prepared on a
      conducting glass (SnO2:F) substrate by solution deposition and electrochemical
      techniques. A uniform CdSe shell layer with a grain size of approximately several
      tens of nanometers was formed on the surface of ZnO nanoneedle cores after
      annealing at 400 degrees C for 1.5 h. Fabricated solar cells based on these
      nanostructures exhibited a high short-circuit current density of about 10.5
      mA/cm2 and an overall power conversion efficiency of 1.07% with solar
      illumination of 100 mW/cm2. Incident photo-to-current conversion efficiencies
      higher than 75% were also obtained.

PMID- 22995032
TI  - Effect of olive and sunflower seed oil on the adult skin barrier: implications
      for neonatal skin care.
AB  - Natural oils are advocated and used throughout the world as part of neonatal skin
      care, but there is an absence of evidence to support this practice. The goal of
      the current study was to ascertain the effect of olive oil and sunflower seed oil
      on the biophysical properties of the skin. Nineteen adult volunteers with and
      without a history of atopic dermatitis were recruited into two randomized forearm
      controlled mechanistic studies. The first cohort applied six drops of olive oil
      to one forearm twice daily for 5 weeks. The second cohort applied six drops of
      olive oil to one forearm and six drops of sunflower seed oil to the other twice
      daily for 4 weeks. The effect of the treatments was evaluated by determining
      stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization,
      skin-surface pH, and erythema. Topical application of olive oil for 4 weeks
      caused a significant reduction in stratum corneum integrity and induced mild
      erythema in volunteers with and without a history of atopic dermatitis. Sunflower
      seed oil preserved stratum corneum integrity, did not cause erythema, and
      improved hydration in the same volunteers. In contrast to sunflower seed oil,
      topical treatment with olive oil significantly damages the skin barrier, and
      therefore has the potential to promote the development of, and exacerbate
      existing, atopic dermatitis. The use of olive oil for the treatment of dry skin
      and infant massage should therefore be discouraged. These findings challenge the
      unfounded belief that all natural oils are beneficial for the skin and highlight
      the need for further research.

PMID- 22995033
TI  - Glasgow coma scale score in the prognosis of acute carbamate insecticide
      intoxication.
AB  - OBJECTIVES: Carbamate is a widely used insecticide, and fatality due to carbamate
      insecticide intoxication has been reported. However, no studies have addressed
      the factors associated with outcome of patients poisoned by carbamate
      insecticide. The present study sought to identify the independent factors that
      could help predict the development of medical complications as a result of
      carbamate intoxication. METHODS: Fifty two patients presenting with acute
      carbamate insecticide ingestion at Chonnam National University Hospital were
      enrolled in this retrospective observational case series. The morbidities that
      needed intensive treatment such as hypotension, respiratory failure, and death
      were regarded as complications. To identify the associated factors to these
      complications, objective variables that are easily assessed at presentation, such
      as age, initial Glasgow coma scale (GSC) and corrected QT (QTc) prolongation,
      were analyzed by univariate and multivariate stepwise logistic regression
      analyses. RESULTS: Of the 52 patients, 35 (67.3%) had medical complications
      within 24 hours after carbamate insecticide intoxication and seven (13.5%) died.
      Respiratory failure was the most common medical complication. The significant
      factors determined by univariate analysis were initial GCS, elevated lactate, and
      QTc prolongation. However, initial GCS (<=13) was the only independent factor
      determined by multivariate analysis that was associated with serious
      complications requiring intensive medical treatment. CONCLUSIONS: Carbamate
      insecticide intoxication is not a mild disease, as previously thought, having a
      mortality rate of 13.8% and a morbidity rate of 67.3%. Initial GCS <= 13 can be
      used as a significant factor to identify carbamate insecticide-intoxicated
      patients who will experience complications.

PMID- 22995034
TI  - Isolated post-challenge hyperglycaemia predicts increased cardiovascular
      mortality.
AB  - OBJECTIVE: The American Diabetes Association (ADA) has revised the criteria for
      the diagnosis of diabetes in 2010. Glycated haemoglobin at a cut-point of >=6.5%
      has been included in the diagnostic algorithm. We aimed to investigate whether
      there is still the need to perform oral glucose tolerance tests (OGTT). METHODS:
      We studied 2002 people referred for angiography who did not have a history of
      diabetes. OGTT were performed in all 1772 subjects with fasting glucose <126
      mg/dl. Participants were prospectively followed for all-cause and cardiovascular
      mortality over a mean duration (+/-standard deviation) of 7.7 +/- 2.0 years.
      RESULTS: Using the ADA 2010 criteria 618 individuals were categorised as having
      new-onset type 2 diabetes. Among these, 167 had isolated post-challenge
      hyperglycaemia. A total of 346 participants died during follow-up. Cardiovascular
      death occurred in 202 cases. Those with elevated fasting glucose >=126 mg/dl
      and/or glycated haemoglobin >=6.5% had increased all-cause (hazard ratio [HR]:
      1.63, 95% confidence interval [95%CI]: 1.28-2.08, p < 0.001) and cardiovascular
      mortality (HR: 1.66, 95%CI: 1.21-2.29, p = 0.002) compared to subjects without
      diabetes according to the ADA 2010 definition. Isolated elevation of post
      challenge glucose independently predicted increased cardiovascular mortality (HR:
      1.57, 95%CI: 1.02-2.43, p = 0.041). All-cause and cardiovascular mortality were
      not significantly different between subjects with increased fasting glucose
      and/or glycated haemoglobin and those with isolated elevation of post-challenge
      glucose. CONCLUSIONS: Performing OGTT will identify a high risk group for
      cardiovascular mortality undetected by fasting glucose or glycated haemoglobin.

PMID- 22995036
TI  - Capwire: a R package for estimating population census size from non-invasive
      genetic sampling.
AB  - Non-invasive genetic sampling is an increasingly popular approach for
      investigating the demographics of natural populations. This has also become a
      useful tool for managers and conservation biologists, especially for those
      species for which traditional mark-recapture studies are not practical. However,
      the consequence of collecting DNA indirectly is that an individual may be sampled
      multiple times per sampling session. This requires alternative statistical
      approaches to those used in traditional mark-recapture studies. Here we present
      the R package capwire, an implementation of the population size estimators of
      Miller et al. (Molecular Ecology 2005; 14: 1991), which were designed to deal
      specifically with this type of sampling. The aim of this project is to enable
      users across platforms to easily manipulate their data and interact with existing
      R packages. We have also provided functions to simulate data under a variety of
      scenarios to allow for rigorous testing of the robustness of the method and to
      facilitate further development of this approach.

PMID- 22995035
TI  - A comparison of Direct sequencing, Pyrosequencing, High resolution melting
      analysis, TheraScreen DxS, and the K-ras StripAssay for detecting KRAS mutations
      in non small cell lung carcinomas.
AB  - BACKGROUND: It is mandatory to confirm the absence of mutations in the KRAS gene
      before treating metastatic colorectal cancers with epidermal growth factor
      receptor inhibitors, and similar regulations are being considered for non-small
      cell lung carcinomas (NSCLC) and other tumor types. Routine diagnosis of KRAS
      mutations in NSCLC is challenging because of compromised quantity and quality of
      biological material. Although there are several methods available for detecting
      mutations in KRAS, there is little comparative data regarding their analytical
      performance, economic merits, and workflow parameters. METHODS: We compared the
      specificity, sensitivity, cost, and working time of five methods using 131 frozen
      NSCLC tissue samples. We extracted genomic DNA from the samples and compared the
      performance of Sanger cycle sequencing, Pyrosequencing, High-resolution melting
      analysis (HRM), and the Conformite Europeenne (CE)-marked TheraScreen DxS and K
      ras StripAssay kits. RESULTS AND CONCLUSIONS: Our results demonstrate that
      TheraScreen DxS and the StripAssay, in that order, were most effective at
      diagnosing mutations in KRAS. However, there were still unsatisfactory
      disagreements between them for 6.1% of all samples tested. Despite this, our
      findings are likely to assist molecular biologists in making rational decisions
      when selecting a reliable, efficient, and cost-effective method for detecting
      KRAS mutations in heterogeneous clinical tumor samples.

PMID- 22995037
TI  - Feasibility for using dual-phase contrast-enhanced multi-detector helical
      computed tomography to evaluate awake and sedated dogs with acute abdominal
      signs.
AB  - Canine patients with acute abdominal signs are often clinically unstable and need
      a rapid and accurate diagnosis. Contrast-enhanced multi-detector computed
      tomography (CT) is the current modality of choice for evaluating acute abdominal
      pain in people. We hypothesized that contrast-enhanced multi-detector CT would be
      a feasible and safe technique for use in awake and lightly sedated dogs with
      acute abdominal signs. Eighteen client-owned dogs were enrolled, all presenting
      with acute abdominal signs. Dogs were scanned using a dual-phase protocol that
      included precontrast, arterial, and portal venous phases. Eight dogs were scanned
      awake and ten were given light sedation as chosen by the primary care clinician.
      Two observers who were unaware of clinical findings and sedation status scored
      image quality for each scan by consensus opinion. Mean serum creatinine in the
      sedated group was higher than in the awake group but was within the normal
      reference range. Other laboratory and physiologic measures did not differ between
      awake and sedated groups. No IV contrast-related adverse reactions were seen.
      Median scan time for all patients was less than 10 min. Sixteen of 18 contrast
      enhanced multi-detector CT scans were scored fair to excellent in diagnostic
      quality, with no statistical difference in diagnostic quality for awake vs.
      sedated patients. Causes for two poor quality diagnostic scans included severe
      beam hardening from previously administered barium contrast agent and severe
      motion artifacts. We conclude that dual-phase contrast-enhanced multi-detector CT
      is a feasible and safe technique for evaluating awake and minimally sedated dogs
      presenting with acute abdominal signs.

PMID- 22995038
TI  - Internalized stigma in schizophrenia: relations with dysfunctional attitudes,
      symptoms, and quality of life.
AB  - Internalized stigma refers to the process by which individuals with mental
      illness apply negative stereotypes to themselves, expect to be rejected by
      others, and feel alienated from society. Though internalized stigma has been
      hypothesized to be associated with maladaptive cognitions and expectations of
      failure, this relationship with dysfunctional attitudes has not been fully
      examined. In the present study, 49 individuals with schizophrenia or
      schizoaffective disorder completed the Internalized Stigma of Mental Illness
      Scale (ISMI; Ritsher et al., 2003) in addition to measures tapping defeatist
      performance beliefs, beliefs regarding low likelihood of success and limited
      resources, negative symptoms, depression, and quality of life. Consistent with
      prior research, internalized stigma was correlated with depression and quality of
      life but not with negative symptoms. Further, internalized stigma was correlated
      with both measures of dysfunctional attitudes. After controlling for depressive
      symptomatology, the relationship between internalized stigma and beliefs
      regarding low likelihood of success and limited resources remained significant,
      and though the correlation between defeatist performance beliefs and internalized
      stigma was no longer significant, it was of a similar magnitude. Overall, these
      data suggest that dysfunctional attitudes play a role in internalized stigma in
      individuals with schizophrenia, indicating a possible point of intervention.

PMID- 22995039
TI  - Mental state decoding and mental state reasoning in recently detoxified alcohol
      dependent individuals.
AB  - Impaired social cognition has been associated with interpersonal problems and
      with the development of and relapse into alcohol abuse. In the present study,
      self-reported trait empathy, decoding of complex mental states and cognitive and
      affective mental state reasoning were assessed in alcohol-dependent participants,
      and the association with executive function and psychopathological
      characteristics was investigated. Twenty recently detoxified alcohol-dependent
      patients and 20 matched healthy controls were assessed with an abbreviated German
      version of the interpersonal reactivity index, the revised reading the mind in
      the eyes test, the faux pas story test, the trail making test and the letter
      number-sequencing test. Patients were impaired relative to controls with regard
      to mental state decoding on the eyes test and showed reduced faux pas detection
      and impaired mental state reasoning reflected by lower faux pas understanding and
      faux pas empathy scores. There were no group differences regarding self-reported
      trait empathy. Performance on the sociocognitive measures was related to
      executive functioning and the severity of depressive symptoms. Although self
      report measures might not always reliably detect impairments of social cognition,
      behavioural measures suggest pronounced impairments of mental state decoding and
      mental state reasoning in association with alcohol dependence. Findings ought to
      be incorporated into current treatment strategies.

PMID- 22995040
TI  - Shortened peginterferon and ribavirin treatment for chronic hepatitis C.
AB  - BACKGROUND: Peginterferon alfa and ribavirin combination therapy is an effective
      treatment for many patients with chronic hepatitis C virus (HCV). Reducing the
      length of treatment may be advantageous. We performed a systematic review and
      economic evaluation to assess shorter treatment duration of this regimen.
      METHODS: We searched fourteen bibliographic databases (including The Cochrane
      Library, Medline, and Embase) from 2000 to October 2009 and consulted experts and
      drug manufacturers. Eligible articles were randomized controlled trials (RCTs)
      selected according to predefined criteria. We undertook an economic evaluation to
      assess the cost-effectiveness of shortened treatment versus standard treatment in
      the UK. RESULTS: Six trials were included. In the sub-group of patients who had
      low viral load (LVL) and a rapid virological response (RVR), there were no
      statistically significant differences in sustained virological response (SVR)
      rates between patients who received standard treatment (range, 83 percent to 100
      percent) and those who received shortened courses (range 84 percent to 96
      percent) (24 weeks for genotype 1, 16 weeks for genotype 2/3). Shortened
      treatment resulted in cost savings, but in some scenarios also resulted in poorer
      outcome, compared with standard treatment. This requires a judgment to be made on
      the value of the quality-adjusted life-year loss resulting from adopting a
      shorter treatment regimen, if shorter treatment is associated with a lower SVR
      than standard treatment duration. CONCLUSIONS: For chronic HCV patients who have
      LVL and achieve an RVR, shortened peginterferon and ribavirin combination therapy
      could be considered as a viable treatment option.

PMID- 22995042
TI  - Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria:
      function, distribution and biomedical implications of the gadBC operon.
AB  - For successful colonization of the mammalian host, orally acquired bacteria must
      overcome the extreme acidic stress (pH < 2.5) encountered during transit through
      the host stomach. The glutamate-dependent acid resistance (GDAR) system is by far
      the most potent acid resistance system in commensal and pathogenic Escherichia
      coli, Shigella flexneri, Listeria monocytogenes and Lactococcus lactis. GDAR
      requires the activity of glutamate decarboxylase (GadB), an intracellular PLP
      dependent enzyme which performs a proton-consuming decarboxylation reaction, and
      of the cognate antiporter (GadC), which performs the glutamatein /gamma
      aminobutyrateout (GABA) electrogenic antiport. Herein we review recent findings
      on the structural determinants responsible for pH-dependent intracellular
      activation of E. coli GadB and GadC. A survey of genomes of bacteria (pathogenic
      and non-pathogenic), having in common the ability to colonize or to transit
      through the host gut, shows that the gadB and gadC genes frequently lie next or
      near each other. This gene arrangement is likely to be important to ensure timely
      co-regulation of the decarboxylase and the antiporter. Besides the involvement in
      acid resistance, GABA production and release were found to occur at very high
      levels in lactic acid bacteria originally isolated from traditionally fermented
      foods, supporting the evidence that GABA-enriched foods possess health-promoting
      properties.

PMID- 22995041
TI  - Patients' knowledge and beliefs concerning gout and its treatment: a population
      based study.
AB  - BACKGROUND: For patients to effectively manage gout, they need to be aware of the
      impact of diet, alcohol use, and medications on their condition. We sought to
      examine patients' knowledge and beliefs concerning gout and its treatment in
      order to identify barriers to optimal patient self-management. METHODS: We
      identified patients (>=18 years of age) cared for in the setting of a
      multispecialty group practice with documentation of at least one health care
      encounter associated with a gout diagnosis during the period 2008-2009 (n =
      1346). Patients were sent a questionnaire assessing knowledge with regard to
      gout, beliefs about prescription medications used to treat gout, and trust in the
      physician. Administrative electronic health records were used to identify
      prescription drug use and health care utilization. RESULTS: Two hundred and forty
      patients returned surveys out of the 500 contacted for participation. Most were
      male (80%), white (94%), and aged 65 and older (66%). Only 14 (6%) patients were
      treated by a rheumatologist. Only a minority of patients were aware of common
      foods known to trigger gout (e.g., seafood [23%], beef [22%], pork [7%], and beer
      [43%]). Of those receiving a urate-lowering medication, only 12% were aware of
      the short-term risks of worsening gout with initiation. These deficits were more
      common in those with active as compared to inactive gout. CONCLUSION: Knowledge
      deficits about dietary triggers and chronic medications were common, but worse in
      those with active gout. More attention is needed on patient education on gout and
      self-management training.

PMID- 22995045
TI  - Synthesis and GC-MS analysis of a series of homologs and regioisomers of 3,4
      methylenedioxypyrovalerone (MDPV).
AB  - A series of ten homologous and regioisomeric aminoketones related to the designer
      synthetic cathinone derivative MDPV were evaluated in this study. These compounds
      were prepared from a common precursor chemical, piperonal (3,4
      methylenedioxybenzaldehyde). These aminoketones show major peaks in their mass
      spectra corresponding to the regioisomeric and homologous immonium cation
      fragments from the loss of the methylenedioxybenzoyl radical species. All ten
      compounds in this study show equivalent EI MS fragments for the 3,4
      methylenedioxybenzoyl fragments (m/z 149) and the methylenedioxybenzene fragment
      at m/z 121. The m/z 149 results from ionization of the carbonyl oxygen followed
      by an alpha-cleavage fragmentation. The loss of CO from this ion yields the m/z
      121 fragments common to all spectra. The regioisomeric aminoketones yield
      equivalent mass spectra including mass equivalent regioisomeric immonium cation
      base peaks. A subset of these compounds has the same molecular weight and almost
      identical mass spectra to that of the designer drug MDPV. An evaluation of the
      effects of homologation on gas chromatographic retention showed that addition of
      a methylene (CH(2)) in the nitrogen-containing ring increases retention more than
      the equivalent group added to the alkyl side-chain.

PMID- 22995043
TI  - Exploring mediators of accelerometer assessed physical activity in young
      adolescents in the Health In Adolescents Study - a group randomized controlled
      trial.
AB  - BACKGROUND: There is a shortage of information about the factors that mediate
      physical activity intervention effects which involve youth. The purpose of this
      study was to examine whether personal, social and physical-environmental factors
      mediated the intervention effect on physical activity and whether gender and
      weight status moderated mediated effects in the Health In Adolescents Study - a
      school-based intervention to promote healthy weight development among young
      adolescents. METHODS: Participating schools were randomized to Control (n = 25)
      and Intervention (n = 12). The intervention components to enhance physical
      activity targeted change through theoretically informed mediators embedded in a
      social-ecological framework. Accelerometer assessed physical activity (mean count
      per minute) and self-efficacy, enjoyment, perceived social support from parents,
      teachers and friends and perceived environmental opportunities were measured by
      questionnaires at baseline and post-intervention after 20 months among 700 11-13
      year-old adolescents (Intervention = 485; Control = 215). The product-of
      coefficient test was used to examine mediation. RESULTS: No mediating effect of
      any of the hypothesized mediators was identified and gender and weight status did
      not moderate any mediated effects with the exception of weight status that
      moderated the mediated effect of enjoyment. Few intervention effects were seen on
      the mediators, except for a positive change in social support from teachers among
      girls and the normal weight, and a negative effect on enjoyment and self-efficacy
      among the overweight. However, change in enjoyment, self-efficacy, perceived
      social support from friends and environmental opportunities were associated with
      change in mean count per minute with some variation across the investigated
      subgroups, and thus show evidence of being potential mediators of physical
      activity change in adolescents. CONCLUSIONS: While no mediation effects were
      observed, change in both personal and social-environmental factors predicted
      change in physical activity behavior. Hence, a social- ecological approach
      targeting a wide range of determinants to promote change in physical activity
      holds promise. Overweight and normal weight adolescents may not respond in the
      same way to school-based physical activity interventions. Therefore, strategies
      to better reach the overweight seem needed. Future studies should continue to
      identify mediating and moderation mechanisms in physical activity change in
      adolescents.

PMID- 22995046
TI  - Detection of metal residues on bone using SEM-EDS--part II: Sharp force injury.
AB  - Scanning electron microscopy coupled with X-ray energy dispersive spectrometry
      (SEM-EDS) is extensively seen in the literature for the improvement of the
      macroscopic analysis of sharp lesions, but very few indications concerning its
      real potential in the forensic context, particularly in forensic anthropology,
      are at the moment available. This paper represents a pilot study for the analysis
      of the behaviour of metallic residues found on bone after sharp force injury.
      Fourteen lesions were made on human bone (radius), cleaned of all soft tissues,
      with seven different sharp tools (three metal instruments, three metal saws and a
      baked-clay knife). Tools and lesions underwent SEM-EDS. From 3 to 18 particles
      were detected on each lesion, whose diameter was included between 0.5 and 150
      MUm. In 58% of cases, particle composition was concordant with the instrument
      used. The results seem to suggest that sharp force injury frequently leaves
      relatively few residues on bone, particularly in the case of common types of
      metal. Saws showed slightly more contamination with other residues than knives,
      which may be explained by the capability of the saw's teeth to retain the
      residues of previously encountered material. In addition, metal residues related
      to the tool used to cut the bone were located on the edges/walls of lesions in
      the case of saw marks, whereas they were more frequently found on the kerf floor
      in the case of knives/scissors, with the exception of the baked clay knife which
      when it leaves residues at all, seemed to leave them equally divided between the
      floor, the edges and the surrounding bone.

PMID- 22995047
TI  - The association between dental status and temporomandibular osseous changes: a
      morphological study on Roman-Byzantine skeletons.
AB  - The aim of this study was to evaluate the association between dental status and
      the prevalence and severity of osseous changes in the temporomandibular joints of
      human skulls from the Roman-Byzantine period. Fifty-eight skulls from 36 men and
      22 women between the ages of 19 and 63 years were studied, and the following
      parameters were evaluated: morphological osseous changes in the articular surface
      of the condyles, tooth wear and molar support. A significant correlation between
      age and dental wear or loss of molar support was observed, although no
      correlation was noted between age and morphological osseous changes in the
      condyles. The loss of molar support was significantly correlated with
      morphological osseous changes of the condyles, whereas no significant correlation
      was found between dental wear and condylar changes. This study demonstrates that
      the loss of molar support can serve as a predictor of osseous changes in the
      condyle. Reduced molar support may be one of the aetiologies associated with
      morphological osseous changes in temporomandibular joints. Further studies should
      to be performed to investigate this potential correlation.

PMID- 22995048
TI  - [Current indications of ileocolonoscopy in children in 2012].
AB  - Indications for ileocolonoscopy were defined in 2002 by the Groupe Francophone
      d'Hepatologie Gastroenterologie et Nutrition. These recommendations were updated
      with new data and technical innovations appearing over the last decade.
      Ileocolonoscopy is primarily indicated for digestive bleeding or anemia and for
      suspected inflammatory bowel disease. It is now indicated in inflammatory bowel
      disease for control of mucosal healing after medical treatment and relapse after
      surgical resection. Iterative ileocolonoscopy is primarily indicated for genetic
      polyposis and well defined for familial adenomatous polyposis. The
      contraindications were not modified.

PMID- 22995049
TI  - The 30 minute rule for red blood cells: in vitro quality assessment after
      repeated exposure to 30 degrees C.
AB  - BACKGROUND: Red blood cells (RBC) may be out of temperature control only for 30
      minutes before they must be discarded, but evidence for this rule is weak. We
      investigated the effect on RBC quality of multiple exposures to 30 degrees C.
      STUDY DESIGN AND METHODS: RBC units made after 24 hours of whole blood ambient
      hold were pooled and split into adult and pediatric units and exposed to
      permitted deviations (5-hr core temperature 10 degrees C, 12-hr surface
      temperature 10 degrees C). Test units were exposed to 30 degrees C once, twice,
      or three times on each of Days 15, 17, and 21, for 30 or 60 minutes. Negative
      controls were not exposed to 30 degrees C; positive control was exposed to 30
      degrees C for 24 hours. RESULTS: Adult units exposed once for 30 or 60 minutes
      (*3 occasions) showed no more hemolysis than negative control. Units exposed to
      30 degrees C for two or three periods of 60 minutes showed more hemolysis from
      Day 28. Hemolysis in pediatric units exposed for 30 minutes (*3) was not
      increased but units exposed to one or two periods of 60 minutes (*3) showed
      higher hemolysis. No differences were seen in supernatant potassium. ATP remained
      at an acceptable level on Day 28 in all but positive controls. CONCLUSIONS: There
      was no evidence of significant damage to RBC after exposure to 30 degrees C for
      three periods of 30 minutes. Multiple exposures of 60 minutes caused limited
      damage but this was within current regulatory limits if there were three or fewer
      exposures, suggesting that a 60-minute rule may be feasible.

PMID- 22995050
TI  - Pain assessment in critical care: instrument selection for nonverbal patients.

PMID- 22995051
TI  - [Realizing systematic cavity margins in conservative breast cancer surgery].
AB  - The quality of surgical margins in lumpectomy are strong criteria to define risk
      of locoregional recurrence when conservative treatment is undertaken.
      Intraoperatively, the limits of adequate resection are sometimes difficult to
      define. This is why some teams propose the realization of systematic cavity
      margins during the excision of lumpectomy during the same operation. We expose
      the potential benefits of this type of practice using data from the literature.

PMID- 22995052
TI  - [How I do... laparoscopic sacrospinous ligament fixation for vaginal vault
      prolapse].

PMID- 22995053
TI  - [Surgical reduction of labia minora: which approach?].
AB  - OBJECTIVES: Surgical approaches for reduction of labia minora are various.
      Through a literature review we try to determine which method is the more
      efficient to treat hypertrophy of labia minora. MATERIALS AND METHODS: A review
      was made by using Medline from 1980 to 2012. The keywords used were "hypertrophy
      of labia minora" and "surgical reduction of labia minora". RESULTS: No randomized
      trial was found. We found only two retrospective studies about triangular
      resection concerning large series of patients, with a long follow-up and precise
      assessment of women satisfaction. DISCUSSION AND CONCLUSION: Surgical approaches
      for hypertrophy of labia minora are various. Triangular resection is the only
      method which was studied for a large series of patients. Functional and aesthetic
      results are good (90 to 95% of cases) and complications are rare (2 to 7%).
      Results of other methods are similar. Consequently, the method must be adjusted
      to surgeon's experience, anatomic features and wish of the patient.

PMID- 22995054
TI  - [Introduction to randomized trials: non-pharmacological treatment interventions].

PMID- 22995055
TI  - [Focus on the complementary specialized studies diploma in reproductive medicine
      for OB GYN residents].

PMID- 22995056
TI  - [Use of magnesium sulfate in obstetrics].
AB  - Magnesium sulfate (MgSO(4)) is the best treatment of eclampsia, reduces the risk
      of recurrence better than other anticonvulsants and is recommended as first line
      in cases of eclampsia. In cases of severe pre-eclampsia and especially when
      prodromes are present, MgSO(4) reduces better than conventional anticonvulsants
      the risk of eclampsia. More recently, MgSO(4) was used in cases of preterm
      delivery to reduce the risk of cerebral palsy in premature infants. Three large
      randomized trials have obtained convergent results which all tended to show a
      neuroprotective effect of MgSO(4). These trials were included in three meta
      analyzes that showed a 30% reduction in the incidence of cerebral palsy before 32
      weeks gestation suggesting that this drug should be used in cases of preterm
      birth. A protocol using low doses associated with a well-conducted maternal
      surveillance reduces of maternal hypermagnesemia and the risk of maternal
      toxicity.

PMID- 22995057
TI  - [Sample size calculation in randomized trials: what the clinician needs to know].

PMID- 22995058
TI  - [The impact of therapeutic management on survival of elderly women with
      endometrial cancer].
AB  - OBJECTIVES: We aimed to determine whether patients characteristics,
      clinicopathologic features and survival rates were worse in elderly women with
      endometrial cancer. PATIENTS AND METHODS: The study cohort consisted of
      consecutive women undergoing surgery for endometrial cancer in our institution
      from January 2000 to October 2011. Patients were divided by age into two groups:
      patients aged 65 to 79 and those aged 80 or older. Clinical data included
      comorbidities, BMI (kg/m(2)), surgical procedures, surgical International
      Federation of Gynecology and Obstetrics (FIGO) stage, histological grade,
      relevant prognostic factors, occurrence of perioperative complications, adjuvant
      therapies, overall survival and long term disease specific mortality. RESULTS: As
      expected, elderly women had more major comorbidities and were less likely to
      undergo optimal surgery, FIGO stages, histological grades. The 5-year disease
      specific survival was significantly poorer for the older group compared to
      younger women 64.5% 95%CI [54.3-73.8] vs 83.49% 95%CI [74.7-90.2] P = 0.008.
      Cancer-specific mortality was also higher in the elderly: 100% vs 41.17% (P =
      0.005). DISCUSSION AND CONCLUSION: Oldest patients with newly diagnosed
      endometrial cancer were found to have worse overall survival and higher cancer
      specific mortality than younger patients because of less aggressive care.
      Clinical efforts must be managed toward the oldest patients with an early stage
      of endometrial cancer to maximize the therapeutic ratio, in particular surgical.

PMID- 22995060
TI  - Do psychiatric units at general hospitals attract less stigmatizing attitudes
      compared with psychiatric hospitals?
AB  - Aims. It is often assumed that psychiatric units at general hospitals attract
      less stigma than do specialized psychiatric hospitals, but so far this has not
      been examined empirically. Methods. We conducted a representative population
      survey in Germany (n = 2410) in order to compare attitudes towards psychiatric
      units and attitudes towards psychiatric hospitals. Two subsamples were presented
      with identical items concerning either psychiatric units or hospitals. We
      conducted multinomial logit analyses of answer categories to detect any
      differences in attitudes. Results. A majority of respondents held favourable
      opinions of psychiatric in-patient care at both psychiatric units and psychiatric
      hospitals. Attitudes towards units and hospitals did not differ meaningfully.
      Conclusions. The influence of location on the image of psychiatric care has been
      over-estimated. We discuss other implications of locating psychiatric care at
      general hospitals.

PMID- 22995059
TI  - The cardiovascular health of urban African Americans: diet-related results from
      the Genes, Nutrition, Exercise, Wellness, and Spiritual Growth (GoodNEWS) trial.
AB  - African Americans have a higher incidence of cardiovascular disease (CVD) than
      Americans in general and are thus prime targets for efforts to reduce CVD risk.
      Dietary intake data were obtained from African Americans participating in the
      Genes, Nutrition, Exercise, Wellness, and Spiritual Growth (GoodNEWS) Trial. The
      286 women and 75 men who participated had a mean age of 49 years; 53% had
      hypertension, 65% had dyslipidemia, and 51% met criteria for metabolic syndrome.
      Their dietary intakes were compared with American Heart Association and National
      Heart, Lung, and Blood Institute nutrition parameters to identify areas for
      improvement to reduce CVD risk in this group of urban church members in Dallas,
      TX. Results from administration of the Dietary History Questionnaire indicated
      median daily intakes of 33.6% of energy from total fat, 10.3% of energy from
      saturated fat, 171 mg cholesterol, 16.3 g dietary fiber, and 2,453 mg sodium. A
      beneficial median intake of 2.9 cups fruits and vegetables per day was coupled
      with only 2.7 oz fish/week and an excessive intake of 13 tsp added sugar/day.
      These data indicate several changes needed to bring the diets of these
      individuals--and likely many other urban African Americans--in line with national
      recommendations, including reduction of saturated fat, sodium, and sugar intake,
      in addition to increased intake of fatty fish and whole grains. The frequent
      inclusion of vegetables should be encouraged in ways that promote achievement of
      recommended intakes of energy, fat, fiber, and sodium.

PMID- 22995061
TI  - Opioid activity profiles of oversimplified peptides lacking in the protonable N
      terminus.
AB  - Recently, we described cyclopeptide opioid agonists containing the d-Trp-Phe
      sequence. To expand the scope of this atypical pharmacophore, we tested the
      activity profiles of the linear peptides Ac-Xaa-Phe-Yaa (Xaa = l/d-Trp, d
      His/Lys/Arg; Yaa = H, GlyNH(2)). Ac-d-Trp-PheNH(2) appeared to be the minimal
      binding sequence, while Ac-d-Trp-Phe-GlyNH(2) emerged as the first
      noncationizable short peptide (partial) agonist with high MU-opioid receptor
      affinity and selectivity. Conformational analysis suggested that 5 adopts in
      solution a beta-turn conformation.

PMID- 22995062
TI  - Relations between the set-complexity and the structure of graphs and their sub
      graphs.
AB  - : We describe some new conceptual tools for the rigorous, mathematical
      description of the "set-complexity" of graphs. This set-complexity has been shown
      previously to be a useful measure for analyzing some biological networks, and in
      discussing biological information in a quantitative fashion. The advances
      described here allow us to define some significant relationships between the set
      complexity measure and the structure of graphs, and of their component sub
      graphs. We show here that modular graph structures tend to maximize the set
      complexity of graphs. We point out the relationship between modularity and
      redundancy, and discuss the significance of set-complexity in this regard. We
      specifically discuss the relationship between complexity and entropy in the case
      of complete-bipartite graphs, and present a new method for constructing highly
      complex, binary graphs. These results can be extended to the case of ternary
      graphs, and to other multi-edge graphs, which are fundamentally more relevant to
      biological structures and systems. Finally, our results lead us to an approach
      for extracting high complexity modular graphs from large, noisy graphs with low
      information content. We illustrate this approach with two examples.

PMID- 22995063
TI  - The hydrolysis kinetics of monobasic and dibasic aminoalkyl esters of ketorolac.
AB  - Six aminoethyl and aminobutyl esters of ketorolac containing 1-methylpiperazine
      (MPE and MPB), N-acetylpiperazine (APE and APB) or morpholine (ME and MB), were
      synthesized and their hydrolysis kinetics were studied. The hydrolysis was
      studied at pH 1 to 9 (for MPE, APE and ME) and pH 1 to 8 (for MPB, APB and MB) in
      aqueous phosphate buffer (0.16 M) with ionic strength (0.5 M) at 37 degrees C.
      Calculation of k(obs), construction of the pH-rate profiles and determination of
      the rate equations were performed using KaleidaGraph(r) 4.1. The hydrolysis
      displays pseudo-first order kinetics and the pH-rate profiles shows that the
      aminobutyl esters, MPE, APB and MB, are the most stable. The hydrolysis of the
      ethyl esters MPE, APE and ME, depending on the pH, is either fast and catalyzed
      by the hydroxide anion or slow and uncatalyzed for the diprotonated,
      monoprotonated and nonprotonated forms. The hydrolysis of the butyl esters showed
      a similar profile, albeit it was also catalyzed by hydronium cation. In addition,
      the hydroxide anion is 105 more effective in catalyzing the hydrolysis than the
      hydronium cation. The hydrolysis pattern of the aminoethyl esters is affected by
      the number and pKa of its basic nitrogen atoms. The monobasic APE and ME, show a
      similar hydrolysis pattern that is different than the dibasic MPE. The length of
      the side chain and the pKa of the basic nitrogen atoms in the aminoethyl moiety
      affect the mechanism of hydrolysis as the extent of protonation at a given pH is
      directly related to the pKa.

PMID- 22995064
TI  - Evaluation of techniques for generation of single-stranded DNA for quantitative
      detection.
AB  - A simple and efficient method for the generation of clean single-stranded DNA
      (ssDNA) with a high recovery and purity from a double-stranded polymerase chain
      reaction (PCR) product is required for nucleic acid sensing and microarray
      applications. Currently, the most widely used technique is thermal denaturation
      due to its simplicity and low cost, but this technique has drawbacks in terms of
      recovery and reproducibility. The work presented here compares this technique
      with alternative approaches for ssDNA generation exploiting affinity magnetic
      separation and exonuclease digestion. The ssDNA recovered was evaluated using gel
      electrophoresis and enzyme-linked oligonucleotide assay. Recoveries of between
      50% and 70% of the theoretical maximum of generatable ssDNA were obtained with
      good reproducibility, demonstrating a marked improvement in performance as
      compared with thermal denaturation.

PMID- 22995065
TI  - A time-resolved fluorescence resonance energy transfer assay suitable for high
      throughput screening for inhibitors of immunoglobulin E-receptor interactions.
AB  - The interaction of immunoglobulin E (IgE) antibodies with the high-affinity
      receptor, FcepsilonRI, plays a central role in initiating most allergic
      reactions. The IgE-receptor interaction has been targeted for treatment of
      allergic diseases, and many high-affinity macromolecular inhibitors have been
      identified. Small molecule inhibitors would offer significant advantages over
      current anti-IgE treatment, but no candidate compounds have been identified and
      fully validated. Here, we report the development of a time-resolved fluorescence
      resonance energy transfer (TR-FRET) assay for monitoring the IgE-receptor
      interaction. The TR-FRET assay measures an increase in fluorescence intensity as
      a donor lanthanide fluorophore is recruited into complexes of site-specific Alexa
      Fluor 488-labeled IgE-Fc and His-tagged FcepsilonRIalpha proteins. The assay can
      readily monitor classic competitive inhibitors that bind either IgE-Fc or
      FcepsilonRIalpha in equilibrium competition binding experiments. Furthermore, the
      TR-FRET assay can also be used to follow the kinetics of IgE-Fc-FcepsilonRIalpha
      dissociation and identify inhibitory ligands that accelerate the dissociation of
      preformed complexes, as demonstrated for an engineered DARPin (designed ankyrin
      repeat protein) inhibitor. The TR-FRET assay is suitable for high-throughput
      screening (HTS), as shown by performing a pilot screen of the National Institutes
      of Health (NIH) Clinical Collection Library in a 384-well plate format.

PMID- 22995066
TI  - Analysis of the phospholipase C-delta1 pleckstrin homology domain using native
      polyacrylamide gel electrophoresis.
AB  - The phospholipase C (PLC)-delta1 pleckstrin homology (PH) domain has a
      characteristic short alpha-helix (alpha2) from residues 82 to 87. The
      contributions of the alpha2-helix toward the inositol 1,4,5-trisphosphate (IP(3))
      binding activity and thermal stability of the PLC-delta1 PH domain were
      investigated using native polyacrylamide gel electrophoresis (PAGE). Native PAGE
      analyses of gel migration shift induced by IP(3) binding and of protein
      aggregation induced by heating indicated that disruption of the alpha-helical
      conformation by replacement of Lys86 with proline resulted in reduced affinity
      for IP(3) and in thermal destabilization of the IP(3)-binding state. Although the
      mutant protein with replacement of Lys86 with alanine showed a slight reduction
      in thermal stability, the IP(3)-binding affinity was similar to that of the wild
      type protein. Replacement of Phe87 with alanine, but not with tyrosine, also
      resulted in reduced affinity for IP(3) and in thermal instability. These results
      indicated that the helical conformation of the alpha2-helix and the phenyl ring
      of Phe87 play important roles in the IP(3)-binding activity and thermal stability
      of the PLC-delta1 PH domain. Based on these results, the biological role of the
      alpha2-helix of the PLC-delta1 PH domain is discussed in terms of membrane
      binding.

PMID- 22995067
TI  - Cigarette smoke impairs granulosa cell proliferation and oocyte growth after
      exposure cessation in young Swiss mice: an experimental study.
AB  - BACKGROUND: Cigarette smoke is associated with decreased female fertility,
      causing damage to ovarian function and disturbing follicle development. However,
      the effects of cigarette toxicants on ovarian function depend on duration and
      intensity of exposure. The aim of this study was to assess the effects of brief,
      intense exposure to tobacco smoke on granulosa cell number, oocyte growth, and
      follicle size during puberty in female Swiss mice. METHODS: Ten female Swiss mice
      aged 35 days were exposed to tobacco smoke from 3R4F reference research
      cigarettes. They were exposed to an automatic smoking machine 8 h/day, 7
      days/week for 15 days. Ten age-matched controls were kept in a different room and
      exposed to ambient air. At the end of 15 days, five mice in each group were
      euthanized and the ovaries were analyzed for follicular morphometry and granulosa
      cell count. The remaining animals were kept for an additional 30 days for further
      analysis as an ex-smoker group and control group. Comparison between the two
      groups was evaluated by the Student's t-test or a two-way ANOVA followed by
      Bonferroni post-test was applied for multiple comparisons. RESULTS: We found that
      cigarette smoke impaired antral follicular growth even after exposure cessation
      (p < 0.001). Both smoking and ex-smoking groups exhibited similar follicle
      diameter. However, at the same follicular stage, the number of granulosa cells
      was smaller in the ex-smoking group compared to smoking animals (p < 0.001). This
      was associated with increased oocyte diameter in ex-smoking animals compared to
      smoking animals (p < 0.01). CONCLUSIONS: The negative effects of cigarette
      smoking seem to last even after exposure has been interrupted. Moreover, brief
      exposure during puberty may induce silent oocyte disruption, which could in turn
      lead to decreased fecundity rates.

PMID- 22995068
TI  - Evolutionary branching in a stochastic population model with discrete mutational
      steps.
AB  - Evolutionary branching is analysed in a stochastic, individual-based population
      model under mutation and selection. In such models, the common assumption is that
      individual reproduction and life career are characterised by values of a trait,
      and also by population sizes, and that mutations lead to small changes epsilon in
      trait value. Then, traditionally, the evolutionary dynamics is studied in the
      limit epsilon->0. In the present approach, small but non-negligible mutational
      steps are considered. By means of theoretical analysis in the limit of infinitely
      large populations, as well as computer simulations, we demonstrate how discrete
      mutational steps affect the patterns of evolutionary branching. We also argue
      that the average time to the first branching depends in a sensitive way on both
      mutational step size and population size.

PMID- 22995069
TI  - Riccardin D-26, a synthesized macrocyclic bisbibenzyl compound, inhibits human
      hepatocellular carcinoma growth through induction of apoptosis in p53-dependent
      way.
AB  - Riccardin D-26 is a synthesized macrocyclic bisbibenzyl compound. We investigated
      the effect of Riccardin D-26 on human hepatocellular carcinomas. Riccardin D-26
      possessed stronger activity against SMMC-7721 cells than human normal liver
      cells. Riccardin D-26 injection effectively delayed the growth of SMMC-7721
      xenografts in mice without significant toxicity. This effect of Riccardin D-26
      was associated with the status of p53 and its targets, bax and
      p21(Waf1)(/)(Cip1). Riccardin D-26 activated p53 expression and induced cancer
      cells to apoptosis through the p53-mediated transcription-dependent and 
      independent pathway. Overall, Riccardin D-26 may inhibit hepatocellular carcinoma
      growth through induction of apoptosis in p53-dependent pathway.

PMID- 22995070
TI  - Increased expression of activated endothelial nitric oxide synthase contributes
      to antiandrogen resistance in prostate cancer cells by suppressing androgen
      receptor transactivation.
AB  - Development of antiandrogen-resistance in advanced prostate cancer involves
      multiple androgen receptor (AR)-dependent and -independent pathways. Here, we
      demonstrated that endothelial nitric oxide synthase (eNOS) exhibited an
      overexpression pattern in hormone-refractory prostate cancer and several models
      of advanced hormone-resistant prostate cancer. We further established a novel in
      vitro model of antiandrogen-resistant prostate cancer (LNCaP-BC) by long-term
      bicalutamide treatment. Besides antiandrogen-resistant and other enhanced
      malignant growth phenotypes, LNCaP-BC cells exhibited an increased activated eNOS
      expression and NO production, and suppressed AR transactivation status. Treatment
      with a NOS inhibitor L-NAME could re-sensitize the growth response to
      bicalutamide and enhance the AR transactivation in LNCaP-BC cells. Together, our
      present findings indicate that increased NO production by acquired increased
      expression of activated eNOS could contribute to the antiandrogen-resistant
      growth of prostate cancer cells, via a mechanism of NO-mediated suppression of AR
      activity, and also targeting eNOS could be a potential therapeutic strategy for
      antiandrogen-resistant prostate cancer.

PMID- 22995071
TI  - Low dose histone deacetylase inhibitor, LBH589, potentiates anticancer effect of
      docetaxel in epithelial ovarian cancer via PI3K/Akt pathway in vitro.
AB  - The purpose of this study was to investigate the effect of combination of LBH589
      with docetaxel (DTX) on the growth and survival of epithelial ovarian cancer
      (EOC) cells in vitro and the possible mechanisms of chemo-sensitization of LBH589
      in the combination treatment. The effect of LBH589 alone or in combination with
      DTX on four EOC cell lines (OVCAR-3, IGROV-1, A2780 and SKOV-3) was studied by
      MTT and clonogenic assays, acridine orange (AO)/ethidium bromide (EB) staining
      for apoptosis, Western blotting for apoptosis-related proteins, histone H3 and H4
      proteins, DNA double strand break (DSB) repair marker and phosphorylation of Akt.
      LBH589 alone inhibited EOC cell proliferation in a time and dose-dependent
      manner. Low-dose of LBH589 (IC(20)) combined with DTX had an additive effect and
      greatly improved efficacy of DTX cell killing in EOC cells. Compared to DTX
      alone, the combination treatment with LBH589 and DTX induced more apoptosis and
      led to an increased and persistent DSB. Cell death following single or combined
      treatment was associated with the release of cytochrome c activity, increased
      caspase-3 (active) and PARP-1(cleaved), histone acetylation-related proteins and
      PI3k/Akt signaling pathway. Our results suggest that LBH589 enhances DTX-induced
      apoptosis in human EOC cells, and can be used in combination with DTX as an
      attractive strategy for treating human EOC.

PMID- 22995072
TI  - Chemistry and integrated services in emerging countries: how is the
      pharmaceutical value chain changing with companies demanding chemistry and other
      services from a provider in emerging countries and what are suppliers doing to
      upgrade the offerings and mitigate the business risk?

PMID- 22995073
TI  - Enabling structure-based drug design of Tyk2 through co-crystallization with a
      stabilizing aminoindazole inhibitor.
AB  - BACKGROUND: Structure-based drug design (SBDD) can accelerate inhibitor lead
      design and optimization, and efficient methods including protein purification,
      characterization, crystallization, and high-resolution diffraction are all needed
      for rapid, iterative structure determination. Janus kinases are important targets
      that are amenable to structure-based drug design. Here we present the first mouse
      Tyk2 crystal structures, which are complexed to 3-aminoindazole compounds.
      RESULTS: A comprehensive construct design effort included N- and C-terminal
      variations, kinase-inactive mutations, and multiple species orthologs. High
      throughput cloning and expression methods were coupled with an abbreviated
      purification protocol to optimize protein solubility and stability. In total, 50
      Tyk2 constructs were generated. Many displayed poor expression, inadequate
      solubility, or incomplete affinity tag processing. One kinase-inactive murine
      Tyk2 construct, complexed with an ATP-competitive 3-aminoindazole inhibitor,
      provided crystals that diffracted to 2.5-2.6 A resolution. This structure
      revealed initial "hot-spot" regions for SBDD, and provided a robust platform for
      ligand soaking experiments. Compared to previously reported human Tyk2 inhibitor
      crystal structures (Chrencik et al. (2010) J Mol Biol 400:413), our structures
      revealed a key difference in the glycine-rich loop conformation that is induced
      by the inhibitor. Ligand binding also conferred resistance to proteolytic
      degradation by thermolysin. As crystals could not be obtained with the unliganded
      enzyme, this enhanced stability is likely important for successful
      crystallization and inhibitor soaking methods. CONCLUSIONS: Practical criteria
      for construct performance and prioritization, the optimization of purification
      protocols to enhance protein yields and stability, and use of high-throughput
      construct exploration enable structure determination methods early in the drug
      discovery process. Additionally, specific ligands stabilize Tyk2 protein and may
      thereby enable crystallization.

PMID- 22995074
TI  - Double-walled hollow polymeric microspheres with independent pH and temperature
      dual-responsive and magnetic-targeting function from onion-shaped core-shell
      structures.
AB  - The magnetic-targeting stimuli-responsive hollow polymeric microspheres show
      unique performance as the intelligent carriers for the site specific controlled
      delivery of drugs or genes. In the work, the well-defied dual-responsive double
      walled hollow microspheres with movable magnetic cores were prepared from the
      penta-layer onion-shaped core-shell microspheres. Their double-walled shells were
      independent, with the pH-responsive crosslinked poly(methacrylic acid) (PMAA)
      layer as the inner shell and the temperature responsive crosslinked poly(N
      isopropylacrylamide) (PNIPAM) layer as the outer shell. The combination of the pH
      and temperature dual-responsive and the magnetic-targeting function make the
      hollow microspheres to be the most promising intelligent carriers in the
      biomedical fields.

PMID- 22995076
TI  - The "big brother".

PMID- 22995075
TI  - An economic model of school-based behavioral interventions to prevent sexually
      transmitted infections.
AB  - OBJECTIVES: Reducing sexually transmitted infections (STI) and teenage pregnancy
      through effective health education is a high priority for health policy.
      Behavioral interventions which teach skills to practice safer sex may reduce the
      incidence of STIs. We evaluated the cost-effectiveness of school-based behavioral
      interventions in young people. METHODS: We developed an economic model to
      estimate the total number of STI cases averted, consequent gain in health related
      quality of life (HRQoL) and savings in medical costs, based on changes in sexual
      behavior. The parameters for the model were derived from a systematic literature
      search on the intervention effectiveness, epidemiology of STIs, sexual behavior
      and lifestyles, HRQoL and health service costs. RESULTS: The costs of providing
      teacher-led and peer-led behavioral interventions were ?5.16 and ?18 per pupil,
      respectively. For a cohort of 1000 boys and 1000 girls aged 15 years, the model
      estimated that the behavioral interventions would avert two STI cases and save
      0.35 Quality Adjusted Life Years (QALYs). Compared to standard education, the
      incremental cost-effectiveness of the teacher-led and peer-led interventions was
      ?24,268 and ?96,938 per QALY gained, respectively. CONCLUSIONS: School-based
      behavioral interventions which provide information and teach young people sexual
      health skills can bring about improvements in knowledge and increased self
      efficacy, though these may be limited in terms of impact on sexual behavior.
      There was uncertainty around the results due to the limited effect of the
      intervention on behavioral outcomes and paucity of data for other input
      parameters.

PMID- 22995077
TI  - Computed tomography to improve TAVI outcomes.

PMID- 22995078
TI  - The "valve" season is upon us.

PMID- 22995079
TI  - Impact of optimising fluoroscopic implant angles on paravalvular regurgitation in
      transcatheter aortic valve replacements - utility of three-dimensional rotational
      angiography.
AB  - AIMS: The clinical value of optimising implant angles during transcatheter aortic
      valve replacements (TAVR) remains undefined. The Aortic Valve Guide (AVG) is a
      proprietary software that provides structured analysis of three-dimensional
      images from rotational angiography (DynaCT). This study compares AVG with
      preprocedural multislice computed tomography (MSCT) and DynaCT in optimal implant
      angle prediction for TAVR, and evaluates if an optimised implant angle is
      associated with reduced paravalvular regurgitation (PVR). METHODS AND RESULTS:
      One hundred and six consecutive patients were included, comprising three groups.
      Group 1 (n=19) underwent no preprocedural MSCT or DynaCT (or AVG); Group 2 (n=44)
      underwent periprocedural DynaCT, without AVG; Group 3 (n=43) had DynaCT with AVG.
      Implant angles yielded were graded as excellent, satisfactory or poor. Group 3
      were more likely than Groups 2 and 1 to have excellent implant angles (83.7% vs.
      52.3% vs. 42.1%, respectively, p=0.001). In 100 patients who had 30-day
      transthoracic echocardiogram follow-up, an excellent implant angle was
      significantly more likely to be associated with no PVR than a non-excellent angle
      (41.3% vs. 21.6%, respectively, p=0.045), independent of operator experience and
      THV used. CONCLUSIONS: Optimising implant angles may be important in reducing
      PVR. This is significantly more likely to be achieved with AVG rotational
      angiography.

PMID- 22995080
TI  - Impact of CT-guided valve sizing on post-procedural aortic regurgitation in
      transcatheter aortic valve implantation.
AB  - AIMS: Transoesophageal echocardiography (TEE) is considered the gold standard
      method for annulus measurement in transcatheter aortic valve implantation (TAVI).
      However, computed tomography (CT) has potential advantages compared to TEE. We
      sought to assess the impact of CT-guided valve sizing on post-procedural aortic
      regurgitation (AR). METHODS AND RESULTS: We compared procedural characteristics
      and clinical outcomes in patients undergoing either TEE-guided or CT-guided TAVI.
      Among 350 consecutive TAVI recipients, the mean age was 83.2 +/- 6.4 years and
      the logistic EuroSCORE was 22.4 +/- 11.2%. The mean Diam-TEE was similar in both
      groups (22.3 +/- 1.9 mm vs. .0 +/- 1.8 mm, p=0.092). The mean annulus diameter by
      CT (mDiam-CT) was larger than mean Diam-TEE (23.6 +/- 2.0 mm vs. 22.3 +/- 1.9 mm,
      p<0.001), and resulted in larger valve implant sizes compared to the TEE-guided
      group (25.8 +/- 2.1 mm vs. 25.0 +/- 1.9 mm, p<0.001). The incidence of post
      procedural AR >= grade 2 was significantly reduced in the CT-guided group (15.4%
      vs. 24.0%, p=0.044), with a similar risk of annulus rupture (0.6% vs. 1.7%,
      p=0.31). The only predictor of post-procedural AR >= 2 was the "valve/mDiam-CT
      ratio" (HR 0.36 by increase of 0.1, 95% CI: 0.17-0.77, p=0.008) by multivariate
      analysis. CONCLUSION: CT-guided valve sizing in TAVI significantly reduces the
      incidence of post-procedural AR compared to TEE sizing. This strategy may have
      the potential to improve clinical outcomes.

PMID- 22995081
TI  - Update on the need for a permanent pacemaker after transcatheter aortic valve
      implantation using the CoreValve(r) AccutrakTM system.
AB  - AIMS: High rates of permanent pacemaker (PPM) implantation are reported after
      transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve(r)
      system. The AccutrakTM catheter is designed to allow a more predictable landing
      zone. Little is known about the real clinical impact of this catheter. The aims
      of this paper were to describe the potential impact of the AccutrakTM catheter on
      the accuracy of positioning a 26 or 29 mm CoreValve(r) across the aortic annulus
      and its impact on the need for a pacemaker. METHODS AND RESULTS: A total of 134
      patients were treated with the CoreValve(r) AccutrakTM system at two French
      centres (Lille and Toulouse). Mean age was 82.4 +/- 4.7 years; logistic EuroSCORE
      was 24.3 +/- 9.5%. Procedural success rate was 99.2%; mean depth of implantation
      was 4.9 mm. A final position between 0 and 6 mm was achieved in 85.8% of the
      patients. All-cause mortality at 30 days was 6%. The PPM implantation rate was
      10.6%. Due to a limited number of events, we could not identify any predictor of
      need for a PPM: pre-existing right bundle branch block (RBBB) (OR 2.72 [0.63
      11.87], p=ns), use of a 29 mm prosthesis (OR 2.73 [0.33-22.90], p=ns) and left
      ventricular septal hypertrophy (OR 2.63 [0.08-83.32], p=ns). CONCLUSIONS: In this
      cohort of patients treated with the CoreValve(r) AccutrakTM system, the incidence
      of permanent pacemaker implantation was low, which may be a consequence of an
      average small implantation depth. The AccutrakTM catheter seems to be helpful in
      achieving higher and more predictable implants. Operators could standardise their
      technique to place the CoreValve(r) prostheses less than 6 mm below the aortic
      annulus.

PMID- 22995082
TI  - The effects of VARC-defined acute kidney injury after transcatheter aortic valve
      implantation (TAVI) using the Edwards bioprosthesis.
AB  - AIMS: The aim of this study was to identify the incidence and risk factors for
      acute kidney injury (AKI) after TAVI, a potentially serious complication of
      transcatheter aortic valve implantation (TAVI) that has been redefined by the
      Valve Academic Research Consortium (VARC). METHODS AND RESULTS: We performed a
      retrospective analysis of 248 patients undergoing TAVI. AKI was defined as a VARC
      modified Risk, Injury, Failure, Loss, and End-stage (RIFLE) kidney disease score
      >= 2. Eighty-nine patients suffered AKI (35.9%) and demonstrated increased
      mortality at 30 days (13.5% vs. 3.8%) and one year (31.5% vs. 15.0%) (p<0.001).
      Multivariate regression analysis identified diabetes mellitus (p<0.001),
      peripheral vascular disease (p=0.007), chronic kidney disease stage (p=0.010) as
      independently associated risk factors for AKI. CONCLUSIONS: More than one third
      of patients sustain AKI after TAVI using the Edwards bioprosthesis, as defined by
      the VARC-modified RIFLE score. AKI increased the mortality at both 30 days and at
      one year. A history of diabetes mellitus, peripheral vascular disease and higher
      chronic kidney disease stage had the strongest independent associations with post
      TAVI AKI.

PMID- 22995083
TI  - Early and mid-term outcomes of percutaneous mitral valve repair with the
      MitraClip(r): comparative analysis of different EuroSCORE strata.
AB  - AIMS: Compare mid-term outcomes after MitraClip(r) implantation for severe mitral
      regurgitation (MR) in patients categorised in different logistic EuroSCORE (LES)
      groups. METHODS AND RESULTS: MitraClip was implanted in 85 patients (78 +/- 6
      years, 48 men [56.5%]) with severe symptomatic MR. Baseline characteristics,
      perioperative results, mid-term survival, major adverse cerebrovascular and
      cardiac events (MACCE), and re-hospitalisation were compared in patients with LES
      <20% (n=30) and >= 20% (n=55). Overall LES was 24 +/- 12 (range 2.5-56.3) and STS
      score 12 +/- 7 (range 1.2-31.2). Overall procedural success rate was 96.5% with
      an in-hospital mortality rate of 3.5%. Echocardiographic and clinical follow-up
      confirmed similar mean transmitral pressure gradient (p=0.13), MR degree
      (p=0.48), and NYHA Class (p=0.93). Estimated six-month survival and freedom from
      composite endpoint was 80.7%/77.1% in LES >= 20% and 90.8/86.6% in LES<20% group,
      respectively (p= 0.014; p=0.018). Multivariate analysis determined LES >= 20%
      (OR=8.1; 95% CI 1.002-65.186), mean transmitral gradient after intervention (OR
      2.5; 95% CI 1.267-5.131) and residual MR (OR=5.1; 95% CI 1.464-17.946) as
      predictors for overall mortality. CONCLUSIONS: LES is a good predictor of
      perioperative results, and follow-up adverse outcomes after MitraClip
      implantation are significantly influenced by the preoperative risk profile. The
      presence of residual MR immediately after MitraClip therapy can exacerbate the
      occurrence of MACCE.

PMID- 22995084
TI  - Transseptal access for MitraClip(r) procedures using surgical diathermy under
      echocardiographic guidance.
AB  - AIMS: Unlike most diagnostic procedures, the MitraClip(r) therapy requires
      precise positioning of transseptal access to ensure a successful procedure.
      Radiofrequency-based transseptal puncture has been developed to reduce
      complications and improve precision of septal access. We report our experience
      utilising surgical diathermy-based transseptal puncture for MitraClip
      implantation. METHODS AND RESULTS: Between October 2008 and April 2010, 72
      patients underwent MitraClip therapy. Diathermy-assisted transseptal access was
      performed in 66 patients, under echocardiographic guidance, by manual contact of
      the diathermy blade with the Brockenbrough needle at the groin. Rate of
      successful puncture, time from femoral vein puncture to transseptal access and
      rate of complications were analysed. Diathermy-assisted puncture was successful
      in all cases. Time from femoral vein access to transseptal puncture was 16 +/- 19
      min. There was one suboptimal septal puncture position (too low), and there was
      one coronary artery air embolism. There were no cases of intraprocedural
      pericardial effusion or arrhythmias. CONCLUSIONS: Surgical diathermy-based
      transseptal puncture may be a safe and effective alternative to either
      conventional or RF-based septal crossing. It improves precision of the septal
      access and may reduce the risk of bleeding complications. This technique is now
      routinely used at our institution for all MitraClip procedures.

PMID- 22995085
TI  - Percutaneous mitral valve repair with the MitraClip(r) system under deep sedation
      and local anaesthesia.
AB  - AIMS: For appropriately selected patients with severe mitral regurgitation,
      percutaneous mitral valve repair with the MitraClip(r) system is a promising
      alternative to open chest surgery. The procedure requires transoesophageal
      echocardiographic guidance and is performed under general anaesthesia. However,
      many patients undergoing percutaneous repair are at high risk for complications
      related to anaesthesia. We report our initial experience in the use of the
      MitraClip(r) system under deep sedation and local anaesthesia in five consecutive
      cases. METHODS AND RESULTS: Five patients (two male, three female), median age 79
      years (range 71 to 88 years), four with moderate to severe mitral regurgitation
      suitable for percutaneous repair, underwent the MitraClip(r) procedure under
      local anaesthesia and deep sedation. All procedures were completed without
      general anaesthesia. All patients received 2 mg of midazolam, and propofol was
      administered according to response during the course of the procedure with 20-60
      mg required per case. The median duration of the procedures was 88 (74 to 193)
      minutes, and the median duration of procedural TEE was 64 (59 to 193) minutes.
      Four of five procedures were carried out successfully. Three patients required
      one clip and one patient required two clips. In one patient, the clip was
      eventually withdrawn and not implanted because it did not lead to an adequate
      reduction of mitral insufficiency. CONCLUSIONS: The implantation of a
      MitraClip(r) is feasible under local anaesthesia and sedation. In patients at
      high risk for complications related to general anaesthesia, percutaneous mitral
      valve repair under local anaesthesia may be a viable alternative.

PMID- 22995086
TI  - The risk and prognostic impact of definite stent thrombosis or in-stent
      restenosis after coronary stent implantation.
AB  - AIMS: Data are limited on the prognostic impact of stent thrombosis and in-stent
      restenosis in patients treated with coronary stents. We examined the prognostic
      impact of stent thrombosis and in-stent restenosis in patients treated with
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: All patients who
      underwent stent implantation from 2002 to 2005 were identified in the Western
      Denmark Heart Registry. The hazard ratio (HR) for death associated with stent
      thrombosis or in-stent restenosis was estimated with a Cox regression analysis
      with stent thrombosis or in-stent restenosis as time-dependent variables. A total
      of 12,277 patients were treated with stent implantation. Stent thrombosis was
      observed in 111 (0.9%) patients and in-stent restenosis in 503 (4.1%) patients
      within 12 months after the index PCI. Occurrence of stent thrombosis was
      associated with an increased risk of death (HR=2.71 [95% CI: 1.72-4.27]) compared
      to cases without stent thrombosis. In-stent restenosis had no substantial impact
      (HR=1.17 [95% CI: 0.79-1.75]). However, in-stent restenosis presenting as non-ST
      segment elevation myocardial infarction (NSTEMI) was associated with a greater
      mortality risk compared with presentation of in-stent restenosis without
      myocardial infarction (HR=3.11 [95% CI: 1.08-8.69]; p=0.036). CONCLUSIONS: The
      occurrence of stent thrombosis and in-stent restenosis presenting with NSTEMI
      increased the mortality risk threefold whereas in-stent restenosis without
      myocardial infarction was not associated with an increased mortality risk.

PMID- 22995087
TI  - Stent thrombosis: insights on outcomes, predictors and impact of dual
      antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and
      COMPARE trials.
AB  - AIMS: Recent studies have suggested that EES may reduce ST compared to PES, but
      no individual trial has been adequately powered for this endpoint. The incidence
      of stent thrombosis, as well as the impact of dual antiplatelet therapy (DAPT)
      discontinuation during the first two years following everolimus-eluting stent
      (EES) and paclitaxel-eluting stent (PES) deployment were therefore analysed from
      a pooled, patient-level database derived from four randomised clinical trials.
      METHODS AND RESULTS: Data from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE
      trials (n=6,789 patients) were analysed. Two-year ST rates were determined using
      time-to-event methods and compared with the log-rank test. ST rates were also
      determined after DAPT discontinuation. EES compared to PES significantly reduced
      the two-year rates of ST (0.7% versus 2.3%, p=0.0001), including the interval
      rates of ST up to 30 days (0.2% versus 1.0%, p<0.0001), between 31 days and one
      year (0.2% versus 0.6%, p=0.02), and after one year (0.3% versus 0.8%, p=0.001).
      EES also reduced the two-year composite rate of cardiac death or MI (4.0% versus
      6.6%, p=0.0001). Increased rates of ST after DAPT discontinuation beyond six
      months were observed in the PES cohort, but not in the EES cohort. CONCLUSION: In
      this large pooled analysis from four randomised trials, treatment with EES
      compared to PES significantly reduced the rates of ST through two years of follow
      up, with a concomitant reduction in cardiac death or MI. DAPT discontinuation
      beyond six months may be safe with EES.

PMID- 22995088
TI  - Proposed practical anatomical-procedural classification systems for evaluating
      carotid lesions and carotid artery stenting.
AB  - AIMS: The aim of this study was to propose new anatomical-procedural
      classification systems for evaluating carotid lesions and carotid artery stenting
      (CAS). METHODS AND RESULTS: The methodology used to propose new concepts to be
      applied in the carotid district was based on three steps: 1) research in PubMed
      with the terms "carotid artery" (CA) plus "classification" was performed in
      August 2010 to verify the existence of any classification system for the CA that
      could be applied for evaluating CAS; 2) formulation of the "stenting segment"
      concept and elaboration of two classification systems - (a) the "ABC" system for
      classifying carotid lesions according to their location, and (b) the "five
      arterial zones" system for identifying specific arterial zones of the CA
      concerning the basics steps of CAS; and 3) retrospective testing of the
      applicability of these classification systems on two hundred and fifty
      consecutive CA angiograms, in which an obstructive lesion was identified. It was
      possible to delimit the "stenting segment", to classify the carotid lesions
      according to the "ABC" classification system and to identify the arterial zones
      according to the "five arterial zones" classification system in all (100%) CA
      angiograms studied. CONCLUSIONS: The "ABC" and the "five arterial zones"
      anatomical-procedural classification systems are applicable in patients with
      obstructive disease of the extracranial CA. These systems may contribute to the
      standardisation of CAS technical evaluation.

PMID- 22995089
TI  - Transcatheter aortic valve implantation: new developments and upcoming clinical
      trials.
AB  - Transcatheter aortic valve implantation (TAVI) is a relatively new technique that
      has been introduced to treat inoperable and high-risk patients with severe aortic
      stenosis. From its early stages it became apparent that TAVI has tremendous
      potentialities and thus a considerable effort was made to design new prostheses
      and advance TAVI technology that would make easier and feasible its application
      in complex anatomies and in patients with multiple comorbidities. In addition,
      evidence from randomised control trials have emerged demonstrating that it
      improves prognosis in inoperable patients (PARTNER trial cohort B) and that it
      can be considered as an attractive alternative to surgery in patients with a high
      operative risk (PARTNER trial cohort A). These encouraging data have motivated
      the scientific community to organise further trials, which will examine the
      performance of new devices and explore the feasibility of TAVI in different
      groups. In this article we review the literature, present the advances in TAVI
      technology, cite the evidence from the already published studies and discuss the
      upcoming clinical trials.

PMID- 22995090
TI  - Percutaneous Edwards SAPIEN valve implantation in the tricuspid position: case
      report and review of literature.
AB  - AIMS: Experience with transcatheter valve-in-valve implantation in a failing
      bioprosthetic tricuspid valve is very limited. Fewer than 30 cases have been
      reported, and in most of them the Melody valve (Medtronic, Inc., Minneapolis, MN,
      USA) was used. With this case report and review of literature we sought to
      evaluate the safety and feasibility of the Edwards SAPIEN transcatheter valve
      (Edwards Lifesciences, Irvine, CA, USA) in valve implantation in the tricuspid
      position and to compare this intervention with the more established Melody valve
      implantation. METHODS AND RESULTS: We describe one of the rarely reported Edwards
      SAPIEN valve implantations in a bioprosthetic tricuspid valve which is also the
      first in a patient with Ebstein's anomaly. A review is presented of all eight
      case reports on Edwards SAPIEN valve implantations in tricuspid position. The
      procedure was successful in all cases. Valve performance after implantation was
      good and no complications were described. In only one procedure pre-stenting was
      performed. Transatrial, transjugular and transfemoral approaches have been used.
      The results are comparable to those of the series about Melody valve-in-valve
      implantation in the tricuspid valve. Mid-term follow-up data are not yet
      available for both valves. CONCLUSIONS: Edwards SAPIEN valve implantation in
      tricuspid bioprosthetic valves is feasible and safe. Considering the available
      sizes of the Edwards SAPIEN valve, it may become the preferred prosthesis for
      valve-in-valve implantation in the tricuspid position in the future.

PMID- 22995091
TI  - The 4 Fr mother-child technique with side-branch protection for treatment of
      complex bifurcation lesions.

PMID- 22995092
TI  - Site of paravalvular leak after mitral valve replacement influences leaflet
      blockage by Amplatzer device.

PMID- 22995093
TI  - Transcatheter aortic valve implantation and closure of the left atrial appendage
      under cerebral protection.

PMID- 22995094
TI  - Regarding "Clinical performance of drug-eluting stents with biodegradable
      polymeric coating: a meta-analysis and systematic review".

PMID- 22995095
TI  - Differences in taste sensitivity between obese and non-obese children and
      adolescents.
AB  - BACKGROUND: Taste sensitivity varies between individuals. Several studies
      describe differences between obese and non-obese subjects concerning their taste
      perception. However, data are partly contradictory and insufficient. Therefore,
      in this study taste sensitivity of obese and non-obese children/adolescents was
      analysed. METHODS: In a cross-sectional study gustatory sensitivity of n=99 obese
      subjects (body mass index (BMI) >97th percentile) and n=94 normal weight subjects
      (BMI <90th percentile), 6-18 years of age, was compared. Sensitivity for the
      taste qualities sweet, sour, salty, umami and bitter was analysed by means of
      impregnated 'taste strips' in different concentrations. A total score was
      determined for all taste qualities combined as well as for each separately.
      Furthermore, the possible influence of sex, age and ethnicity on taste perception
      was analysed. An intensity rating for sweet was performed on a 5-point rating
      scale. RESULTS: Obese subjects showed-compared to the control group-a
      significantly lower ability to identify the correct taste qualities regarding the
      total score (p<0.001). Regarding individual taste qualities there was a
      significantly lower detection rate for salty, umami and bitter by obese subjects.
      Furthermore, the determinants age and sex had a significant influence on taste
      perception: older age and female sex was associated with better ability to
      identify taste qualities. Concerning the sweet intensity rating obese children
      gave significantly lower intensity ratings to three of the four concentrations.
      CONCLUSIONS: Obese and non-obese children and adolescents differ in their taste
      perception. Obese subjects could identify taste qualities less precisely than
      children and adolescents of normal weight.

PMID- 22995097
TI  - Effect of alkylphospholipids on Candida albicans biofilm formation and
      maturation.
AB  - OBJECTIVES: The aim of this study was to evaluate miltefosine and four synthetic
      compounds (TCAN26, TC19, TC106 and TC117) for their in vitro inhibitory activity
      against Candida albicans planktonic and biofilm cells and investigate whether
      these compounds are able to inhibit the biofilm formation and to reduce the
      viability of mature C. albicans biofilm cells. METHODS: The XTT reduction assay
      and transmission and scanning electron microscopy were employed to determine the
      inhibitory effects of the test compounds in comparison with amphotericin B and
      fluconazole against both planktonic cells and sessile cells in biofilms. RESULTS:
      C. albicans planktonic cells were susceptible to miltefosine, TCAN26 and TC19,
      all alkylphospholipid compounds. Miltefosine and TCAN26 present a fungicidal
      activity with similar values of MIC and minimum fungicidal concentration (MFC),
      ranging from 2 to 8 mg/L. Cell treatment with sub-inhibitory concentrations of
      alkylphospholipids induced several ultrastructural alterations. In relation to
      biofilms, miltefosine reduced formation (38%-71%) and mature biofilms viability
      (32%-44%), at concentrations of 64 mg/L. TCAN26 also reduced biofilm formation
      (24%-30%) and mature biofilm viability (15%-20%), at concentrations of 64 mg/L.
      Although amphotericin B reduced biofilm formation similarly to miltefosine (51%
      74%), its activity was lower on mature biofilms (24%-30%). Miltefosine
      antibiofilm activity was significantly higher than amphotericin B, on both
      formation and mature biofilms (P<0.05 and P<0.0001, respectively). Fluconazole
      was the least effective compound tested. CONCLUSION: Promising antibiofilm
      activity was displayed by miltefosine and other alkylphosphocholine compounds,
      which could be considered a putative option for future treatment of candidaemia
      associated with biofilm formation, although further evaluation in in vivo systems
      is required.

PMID- 22995096
TI  - National standards for diabetes self-management education and support.

PMID- 22995098
TI  - Breast cancer screening: are we seeing the benefit?
AB  - A decline in breast cancer mortality has been observed in western European
      Countries since the middle of the 1990s. Different methodological approaches,
      including case-control studies, incidence-based mortality studies, and trend
      studies, have been used to assess the effectiveness of mammography screening
      programmes in reducing breast cancer mortality. However, not all methods succeed
      in distinguishing the relative contributions of service screening and taking
      correctly into consideration the potential source of bias that might affect the
      estimate. Recently, a review of six case-control studies confirmed a breast
      cancer mortality reduction ranging from 38% to 70% among screened women. This
      figure is in accordance with the estimate obtained from incidence-based mortality
      studies if screening compliance is taken into account. We will describe the
      methodological constraints of mortality trend studies in predicting the impact of
      screening on mortality and the necessary caution that must be applied when
      interpreting the results of such studies. In conclusion, when appropriate
      methodological approaches are used, it is evident that mammographic screening
      programmes have contributed substantially to the observed decline in breast
      cancer mortality.

PMID- 22995099
TI  - Clinical Heterogeneity in two patients with Noonan-like Syndrome associated with
      the same SHOC2 mutation.
AB  - Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been
      recently related to the invariant c.4A > G missense change in SHOC2. It is
      characterized by features reminiscent of Noonan syndrome. Ectodermal involvement,
      short stature associated to growth hormone (GH) deficiency (GHD), and cognitive
      deficits are common features. We compare in two patients with molecularly
      confirmed NS/LAH diagnosis, the clinical phenotype and pathogenetic mechanism
      underlying short stature. In particular, while both the patients exhibited a
      severe short stature, GH/IGFI axis functional evaluation revealed a different
      pathogenetic alteration, suggesting in one patient an upstream alteration
      (typical GHD) and in the other one a peripheral GH insensitivity. 

PMID- 22995100
TI  - Is dignity therapy feasible to enhance the end of life experience for people with
      motor neurone disease and their family carers?
AB  - BACKGROUND: Development of interventions that address psychosocial and
      existential distress in people with motor neurone disease (MND) or that alleviate
      caregiver burden in MND family carers have often been suggested in the research
      literature. Dignity therapy, which was developed to reduce psychosocial and
      existential distress at the end of life, has been shown to benefit people dying
      of cancer and their families. These results may not be transferable to people
      with MND. The objectives of this study are to assess the feasibility,
      acceptability and potential effectiveness of dignity therapy to enhance the end
      of life experience for people with motor neurone disease and their family carers.
      METHODS/DESIGN: This is a cross-sectional study utilizing a single treatment
      group and a pre/post test design. The study population will comprise fifty people
      diagnosed with MND and their nominated family carers. Primarily quantitative
      outcomes will be gathered through measures assessed at baseline and at
      approximately one week after the intervention. Outcomes for participants include
      hopefulness, spirituality and dignity. Outcomes for family carers include
      perceived caregiver burden, hopefulness and anxiety/depression. Feedback and
      satisfaction with the intervention will be gathered through a questionnaire.
      DISCUSSION: This detailed research will explore if dignity therapy has the
      potential to enhance the end of life experience for people with MND and their
      family carers, and fill a gap for professionals who are called on to address the
      spiritual, existential and psychosocial needs of their MND patients and families.
      TRIAL REGISTRATION: ACTRN Trial Number: ACTRN12611000410954.

PMID- 22995101
TI  - Making processes reliable: a validated pubmed search strategy for identifying new
      or emerging technologies.
AB  - BACKGROUND AND OBJECTIVES: Horizon scanning systems need to handle a wide range
      of sources to identify new or emerging health technologies. The objective of this
      study is to develop a validated Medline bibliographic search strategy (PubMed
      search engine) to systematically identify new or emerging health technologies.
      METHODS: The proposed Medline search strategy combines free text terms commonly
      used in article titles to denote innovation within index terms that make
      reference to the specific fields of interest. Efficacy was assessed by running
      the search over a period of 1 year (2009) and analyzing its retrieval performance
      (number and characteristics). For comparison purposes, all article abstracts
      published during 2009 in six preselected key research journals and eight high
      impact surgery journals were scanned. Sensitivity was defined as the proportion
      of relevant new or emerging technologies published in key journals that would be
      identified in the search strategy within the first 2 years of publication.
      RESULTS: The search yielded 6,228 abstracts of potentially new or emerging
      technologies. Of these, 459 were classified as new or emerging (383 truly new or
      emerging and 76 new indications). The scanning of 12,061 journal abstracts
      identified 35 relevant new or emerging technologies. Of these, twenty-nine were
      located within the Medline search strategy during the first 2 years of
      publication (sensitivity = 83 percent). CONCLUSIONS: The current search strategy,
      validated against key journals, has demonstrated to be effective for horizon
      scanning. Even though it can require adaptations depending on the scope of the
      horizon scanning system, it could serve to simplify and standardize scanning
      processes.

PMID- 22995102
TI  - The Institute of Medicine's new report on living well with chronic illness.

PMID- 22995103
TI  - Evaluation of consumer understanding of different front-of-package nutrition
      labels, 2010-2011.
AB  - INTRODUCTION: Governments throughout the world are using or considering various
      front-of-package (FOP) food labeling systems to provide nutrition information to
      consumers. Our web-based study tested consumer understanding of different FOP
      labeling systems. METHODS: Adult participants (N = 480) were randomized to 1 of 5
      groups to evaluate FOP labels: 1) no label; 2) multiple traffic light (MTL); 3)
      MTL plus daily caloric requirement icon (MTL+caloric intake); 4) traffic light
      with specific nutrients to limit based on food category (TL+SNL); or 5) the
      Choices logo. Total percentage correct quiz scores were created reflecting
      participants' ability to select the healthier of 2 foods and estimate amounts of
      saturated fat, sugar, and sodium in foods. Participants also rated products on
      taste, healthfulness, and how likely they were to purchase the product. Quiz
      scores and product perceptions were compared with 1-way analysis of variance
      followed by post-hoc Tukey tests. RESULTS: The MTL+caloric intake group (mean
      [standard deviation], 73.3% [6.9%]) and Choices group (72.5% [13.2%])
      significantly outperformed the no label group (67.8% [10.3%]) and the TL+SNL
      group (65.8% [7.3%]) in selecting the more healthful product on the healthier
      product quiz. The MTL and MTL+caloric intake groups achieved average scores of
      more than 90% on the saturated fat, sugar, and sodium quizzes, which were
      significantly better than the no label and Choices group average scores, which
      were between 34% and 47%. CONCLUSION: An MTL+caloric intake label and the Choices
      symbol hold promise as FOP labeling systems and require further testing in
      different environments and population subgroups.

PMID- 22995104
TI  - Symetis ACURATE TA valve.
AB  - The transcatheter aortic valve prosthesis ACURATE TA (Symetis SA, Ecublens,
      Switzerland) has been specifically designed for transapical access with a future
      transfemoral version under development. The concept relies on a self-expandable
      nitinol stent housing a regular porcine bioprosthesis. A unique two-step
      implantation technique facilitates intuitive positioning. Two pre-approval
      multicentre trials have demonstrated promising results especially as regards a
      low rate of paravalvular leaks. The device obtained CE mark at the end of 2011
      and is currently commercially available in Europe. This manuscript focuses on the
      technical details of this new transapical TAVI device and its specific
      implantation technique.

PMID- 22995105
TI  - Building on the shoulders of giants: the Valve Academic Research Consortium
      (VARC) initiative towards a global framework to guide valvular heart disease
      trials.

PMID- 22995106
TI  - Historical perspective: 10th year anniversary of TAVI.

PMID- 22995107
TI  - Mechanisms and prediction of aortic regurgitation after TAVI.
AB  - It has been demonstrated that moderate to severe paravalvular leak (PVL) after
      transcatheter aortic valve implantation (TAVI) procedures are related to impaired
      long-term prognosis. Anatomical and procedural factors influence the frequency
      and severity of PVL. Anatomical predictors of this complication are: annulus
      dimensions and shape, calcium distribution, angle between the ascending aorta
      axis and the left ventricular outflow tract (LVOT-AO). Procedural predictors:
      prosthesis-size-annulus mismatch, valve depth deployment and the acquired
      experience of the centre. An effort has to be made to optimise valve sizing and
      deployment.

PMID- 22995108
TI  - Imaging and quantification of aortic regurgitation after TAVI.
AB  - During the last decade, transcatheter aortic valve implantation (TAVI) techniques
      have evolved rapidly providing several systems that conform to a broad spectrum
      of aortic valve annulus sizes, developing new delivery systems that provide an
      alternative to patients with difficult vascular access and permitting more
      controlled and accurate prosthesis deployment that result in improved procedural
      outcomes. However, residual aortic regurgitation (AR) (paravalvular or
      transvalvular) remains a recurrent observation and patients with moderate or
      severe AR have a reduced mid-term prognosis Therefore, postprocedural AR should
      be carefully and accurately evaluated in order to decide whether additional
      procedures such as re-ballooning or valve-in-valve are needed to reduce AR
      severity, and changes in AR at follow-up should be monitored. In the current
      review, the role of cardiac imaging to understand the mechanism underlying AR
      after TAVI and to quantify the severity of AR will be discussed.

PMID- 22995109
TI  - Prognostic impact of aortic regurgitation after transcatheter aortic valve
      implantation.
AB  - Aortic regurgitation (AR) is an important predictor of adverse prognosis after
      transcatheter aortic valve implantation (TAVI) by both self-expanding and balloon
      expandable prostheses and is predominantly paravalvular (PV). The mounting
      evidence for moderate/severe PV AR as an independent predictor of mortality is
      discussed. Moreover, there is an unclear impact on prognosis of mild PV AR that
      is most likely the result of imperfect assessment of this complication, which
      currently remains semi-quantitative. The relevance of its accurate quantification
      to reliable prognostication is described, along with how this data might be used
      to guide intervention and optimise outcomes of patients with PV AR.

PMID- 22995110
TI  - Treatment and prevention of aortic regurgitation after transcatheter aortic valve
      implantation.
AB  - Significant aortic regurgitation (AR) after transcatheter aortic valve
      implantation (TAVI) has been shown to be associated with worse mid-term outcome.
      The two-year follow-up results of the PARTNER US trial showed that not only >=3/4
      AR grade, but also grade 2 had a significant impact on mortality. Thus,
      prevention and treatment of significant AR after TAVI is of great importance.
      Usually, AR after TAVI consists mostly of paravalvular leak and significant
      central AR is uncommon. Here we describe measures to decrease the risk of AR
      after TAVI which are currently available.

PMID- 22995111
TI  - Paravalvular leaks: mechanisms, diagnosis and management.
AB  - AIMS: To understand the incidence, aetiology and mechanisms of paravalvular
      aortic and mitral leaks after valvular surgery; reviewing the best methods for
      diagnosis, procedural guidance and result assessment of these leaks, as well as
      describing the different approaches to their treatment. METHODS AND RESULTS: A
      literature search was undertaken as well as an in-depth analysis of our own
      experience concerning different imaging modalities and various therapeutic
      strategies for aortic and mitral paravalvular leaks. The majority of patients
      were diagnosed using two- or three-dimensional transoesophageal echocardiography,
      useful in both guiding the procedure as well as assessing the procedural results.
      Haemoglobin, haematocrit, LDH and haptoglobin values were analysed to assess
      haemolysis. Procedural success for percutaneous closure of paravalvular aortic
      leaks are around 90% in the different series, with low complication rates. Mitral
      leaks have been approached by transfemoral and transapical access; the reported
      success of this procedure ranges from 75% to more than 90% in different reports.
      Complication rates at 30 days average 10% and mortality related to the procedure
      is around 1%. Late follow-up results depend on the initial anatomy, baseline
      clinical class and procedure results. CONCLUSIONS: Paravalvular leaks after
      surgical valve implantation have a multifactorial aetiology, but are mainly
      related to specific anatomic characteristics of the valvular ring. Mitral leaks
      are three times more common than aortic leaks and the incidence increases after
      reoperation. Different percutaneous techniques with several devices have been
      explored for leak closure, but we are still lacking devices specifically designed
      to treat this pathology more effectively.

PMID- 22995112
TI  - Transcatheter mitral valve interventions: current status and future perspective.
AB  - AIMS: With the recent developments in the field of transcatheter aortic valve
      replacement for aortic stenosis there has been a similar advance in the field of
      transcatheter mitral valve therapy for mitral regurgitation (MR). Both the
      anatomy of the mitral apparatus and the spectrum of pathology of MR are more
      complex than for aortic valve disease, and thus the development of MR therapies
      has been more complicated and less rapid. METHODS AND RESULTS: The purpose of
      this review of recent literature is to provide a synopsis of the present
      technologies under development for percutaneous therapy for MR. Leaflet repair
      with MitraClip has accrued the largest human experience among the technologies
      that are under development, having been used to treat over 6,000 patients.
      MitraClip is currently being used in patients with functional MR and at high risk
      for conventional surgery. Coronary sinus, or indirect annuloplasty, has the next
      largest clinical experience, with several hundred patients treated in trials.
      Other MR therapy devices, including several direct annuloplasty approaches,
      mitral valve replacement prostheses, and chordal replacement devices, are still
      in the earlier phases of development. CONCLUSIONS: The early technological
      advances have not only enhanced our understanding of the complex interplay of
      different components of the mitral valve apparatus but also promise continued
      refinement in our present modalities of treatment and improved clinical outcomes
      for future patients.

PMID- 22995113
TI  - Transcatheter aortic valve implantation and cerebrovascular accidents.
AB  - Transcatheter aortic valve implantation (TAVI) is an evidence-based treatment
      alternative for selected high-risk patients with symptomatic severe aortic
      stenosis as acknowledged in the most recent edition of the ESC Guidelines on
      Valvular Heart Disease 2012. However, periprocedural complications and in
      particular cerebrovascular accidents remain a matter of concern. While
      transcatheter heart valve technology continuously improves and the development of
      novel and even less invasive implantation techniques is on-going, cerebrovascular
      events complicating TAVI may abrogate the usual improvement in terms of prognosis
      and quality of life. This article describes the incidence of cerebrovascular
      events after cardiovascular procedures, provides an overview of the
      pathophysiological mechanisms as well as the impact on outcomes and provides some
      insights into preventive strategies as well as the acute management of these
      events.

PMID- 22995114
TI  - Welcome to PCR London Valves 2012.

PMID- 22995115
TI  - Boston Scientific Lotus valve.
AB  - As a result of recent randomised controlled trials and registry observations,
      transcatheter aortic valve replacement (TAVR) enjoys growing appeal for the
      treatment of patients at high or extreme risk from surgical aortic valve
      replacement. However, the current technologies and techniques have important
      limitations, including risk of stroke, vascular complications and paravalvular
      aortic regurgitation, which may in turn influence survival. While careful patient
      selection and screening may improve outcomes, new valve designs and iterations
      are required. The Lotus aortic valve replacement system is a new fully
      repositionable device designed to facilitate more precise delivery and minimise
      paravalvular regurgitation. The safety and efficacy of the Lotus valve are being
      studied systematically in the REPRISE clinical trial programme.

PMID- 22995117
TI  - Edwards CENTERA valve.
AB  - Transcatheter aortic valve implantation (TAVI) has been adopted worldwide as a
      prominent therapeutic alternative for patients with high-risk severe symptomatic
      aortic stenosis. Despite its more widespread adoption as a treatment option and
      the increasing experience of the centres, TAVI is still associated with
      complications. Therefore, improvements in transcatheter heart valve (THV)
      technology, such as optimisation of device function with superior deliverability,
      and valve repositioning, are desirable. Accordingly, this article describes the
      new self-expandable Edwards CENTERA THV, made of nitinol and treated bovine
      pericardial tissue, and delivered by a motorised low-profile delivery system
      which potentially permits accurate valve placement and valve repositioning by a
      single operator. First-in-human clinical experience with the CENTERA THV has been
      promising but larger series with longer follow-up are warranted to confirm these
      initial positive results.

PMID- 22995116
TI  - Direct Flow Medical valve.
AB  - AIMS: To study the feasibility and safety of the non-metallic, repositionable and
      retrievable percutaneous Direct Flow Medical (DFM) aortic valve. METHODS AND
      RESULTS: The first-generation (22 Fr) DFM valve has been evaluated in a
      prospective non-randomised trial in 31 high-risk patients with severe symptomatic
      aortic stenosis. The procedural success rate was 71%, 30-day mortality 12.9%.
      Survival at three years was 60% and all patients had none/trace aortic
      regurgitation at three years. Based on the initial experience, an 18 Fr device
      has been developed with several important revisions to improve the efficacy and
      safety of the procedure. Currently, it is being evaluated in a multicentre non
      randomised trial which will include 100 patients. The primary endpoint is freedom
      from all-cause mortality at 30 days. CONCLUSIONS: The 22 Fr DFM valve has been
      successfully assessed in a first-in-man feasibility and safety trial. Up to three
      year follow-up sustained clinical benefit and haemodynamic performance was
      demonstrated with no or trace aortic regurgitation in all patients. The 18 Fr DFM
      valve is under investigation in an on-going trial.

PMID- 22995118
TI  - Edwards SAPIEN 3 valve.
AB  - Building on the established success with the SAPIEN, SAPIEN XT and earlier
      prototypic transcatheter heart valves (THV) the newest balloon-expandable valve
      incorporates a number of new and enhanced features intended to reduce the risk of
      vascular injury, to reduce paravalvular regurgitation, and to facilitate rapid
      and accurate positioning and implantation. The SAPIEN 3 THV incorporates a cobalt
      chromium stent, bovine pericardial leaflets, and both an inner and new outer
      polyethylene terephthalate sealing cuff. The delivery system incorporates an
      active three-dimensional coaxial positioning catheter, and is compatible with a
      14 Fr expandable sheath.

PMID- 22995119
TI  - JenaValve.
AB  - The JenaValve is a next-generation TAVI device which consists of a well-proven
      porcine root valve mounted on a low-profile nitinol stent. Feeler guided
      positioning and clip fixation on the diseased leaflets allow for anatomically
      correct implantation of the device without rapid pacing. Safety and efficacy of
      transapical aortic valve implantation using the JenaValve were evaluated in a
      multicentre prospective study that showed good short and midterm results. The
      valve was CE-mark released in Europe in September 2011. A post-market registry
      ensures on-going and prospective data collection in "real-world" patients. The
      transfemoral JenaValve delivery system will be evaluated in a first-in-man study
      in the near future.

PMID- 22995120
TI  - PCR London Valves: a global course on valvular heart disease under the auspices
      of PCR and EAPCI.

PMID- 22995121
TI  - Medtronic CoreValve Evolut valve.
AB  - The first member of the next generation CoreValve "family" is the 23 mm
      CoreValve(r) EvolutTM (Medtronic, Minneapolis, MN, USA), which is indicated for
      an annulus range of 18 mm to 20 mm and extends the spectrum of patients with
      aortic stenosis that can be treated with the self-expanding CoreValve
      bioprosthesis. The Core-Valve Evolut provides several technical refinements and
      is designed to enable re-capturability in the future. Here, we report on the
      first case in a 93-year-old female patient who was implanted at the University
      Hospital Bonn, Germany, on June 1st, 2012.

PMID- 22995122
TI  - St Jude Medical Portico valve.
AB  - Transcatheter aortic valve implantation is increasingly being used to treat high
      risk patients with symptomatic aortic valve disease. However, challenges still
      remain with current devices, both in terms of the procedure and the outcome. The
      St Jude Medical Portico transcatheter valve system is designed to mitigate some
      of these difficulties. We describe the device characteristics and how the device
      may impact on a TAVI procedure. An overview of the clinical experiences with the
      Portico valve system is also described.

PMID- 22995124
TI  - Acute adrenal failure as the presenting feature of primary antiphospholipid
      syndrome in a child.
AB  - INTRODUCTION: Antiphospholipid syndrome (APS) is characterized by recurrent
      arterial and venous thrombosis and detection of antiphospholipid antibodies
      (aPLs). This syndrome may be associated with connective tissue disorders, or with
      malignancies, but it may also appear in isolated form (primary APS). We report on
      a pediatric patient presenting with acute adrenal failure as the first
      manifestation of primary APS. CASE REPORT: A previously healthy 11-year-old boy
      developed fever, abdominal pain, and vomiting. An abdominal computed tomography
      scan showed nodular lesions in the adrenal glands. He was referred to our
      Department and a diagnosis of APS and acute adrenal failure was considered, based
      on positive aPLs (IgG and IgM), elevated ACTH levels and low cortisol levels.
      Other features were anemia, thrombocytopenia, elevated inflammatory parameters,
      hypergammaglobulinemia, prolonged partial thromboplastin time, positive
      antinuclear, anticardiolipin, anti-platelet antibodies, with negative double
      stranded DNA antibodies. Lupus anticoagulant and Coomb's tests were positive. MRI
      revealed a bilateral adrenal hemorrhage. A treatment with intravenous
      metylprednisolone, followed by oral prednisone and anticoagulant, was started,
      resulting in a progressive improvement. After 2 months he also showed
      hyponatremia and elevated renine levels, indicating a mineralcocorticoid
      deficiency, requiring fludrocortisones therapy. CONCLUSION: The development of
      acute adrenal failure from bilateral adrenal haemorrhage in the context of APS is
      a rare but life-threatening event that should be promptly recognized and treated.
      Moreover, this case emphasizes the importance of the assessment of aPLs in
      patients with acute adrenal failure in the context of an autoreaction.

PMID- 22995125
TI  - Primary Health Care in rural Malawi - a qualitative assessment exploring the
      relevance of the community-directed interventions approach.
AB  - BACKGROUND: Primary Health Care (PHC) is a strategy endorsed for attaining
      equitable access to basic health care including treatment and prevention of
      endemic diseases. Thirty four years later, its implementation remains sub-optimal
      in most Sub-Saharan African countries that access to health interventions is
      still a major challenge for a large proportion of the rural population. Community
      directed treatment with ivermectin (CDTi) and community-directed interventions
      (CDI) are participatory approaches to strengthen health care at community level.
      Both approaches are based on values and principles associated with PHC. The CDI
      approach has successfully been used to improve the delivery of interventions in
      areas that have previously used CDTi. However, little is known about the added
      value of community participation in areas without prior experience with CDTi.
      This study aimed at assessing PHC in two rural Malawian districts without CDTi
      experience with a view to explore the relevance of the CDI approach. We examined
      health service providers' and beneficiaries' perceptions on existing PHC
      practices, and their perspectives on official priorities and strategies to
      strengthen PHC. METHODS: We conducted 27 key informant interviews with health
      officials and partners at national, district and health centre levels; 32 focus
      group discussions with community members and in-depth interviews with 32
      community members and 32 community leaders. Additionally, official PHC related
      documents were reviewed. RESULTS: The findings show that there is a functional
      PHC system in place in the two study districts, though its implementation is
      faced with various challenges related to accessibility of services and shortage
      of resources. Health service providers and consumers shared perceptions on the
      importance of intensifying community participation to strengthen PHC,
      particularly within the areas of provision of insecticide treated bed nets, home
      case management for malaria, management of diarrhoeal diseases, treatment of
      schistosomiasis and provision of food supplements against malnutrition.
      CONCLUSION: Our study indicates that intensified community participation based on
      the CDI approach can be considered as a realistic means to increase accessibility
      of certain vital interventions at community level.

PMID- 22995126
TI  - Implementation of local/hospital-based health technology assessment initiatives
      in low- and middle-income countries.
AB  - OBJECTIVES: The objective of this study is to review the implementation of health
      technology assessment (HTA) at the local and hospital levels in low- and middle
      income countries (LMIC). This review will provide a starting point for
      identifying the conditions for HTA implementation in hospitals in LMIC through
      the analysis of experiments conducted in these countries. METHODS: A systematic
      review of the literature was conducted to document the local-/hospital-level HTA
      experiments performed in LMIC. RESULTS: This systematic review showed that few
      experiments of local HTA in LMIC have been published to date, with only five
      articles found in our survey. These documents report studies of clinical
      effectiveness and economic evaluation at the local level in certain Asian and
      Latin American countries. In addition, pharmaceuticals and medical devices were
      the most common topics covered by HTA at the local level in these countries.
      CONCLUSIONS: Currently, HTA plays an increasingly important role in healthcare
      systems in supporting decision making for healthcare policies and practices. This
      systematic review contributes to identify priorities in the process and
      methodology of HTA implementation at the local/hospital level in LMIC. The
      paucity of HTA in LMIC is often assumed to be due to the lack of formally tasked
      HTA agencies, to politics and to shortage of resources.

PMID- 22995123
TI  - HIV-1 subtype C superinfected individuals mount low autologous neutralizing
      antibody responses prior to intrasubtype superinfection.
AB  - BACKGROUND: The potential role of antibodies in protection against intra-subtype
      HIV-1 superinfection remains to be understood. We compared the early neutralizing
      antibody (NAb) responses in three individuals, who were superinfected within one
      year of primary infection, to ten matched non-superinfected controls from a
      Zambian cohort of subtype C transmission cases. Sequence analysis of single
      genome amplified full-length envs from a previous study showed limited
      diversification in the individuals who became superinfected with the same HIV-1
      subtype within year one post-seroconversion. We hypothesized that this reflected
      a blunted NAb response, which may have made these individuals more susceptible to
      superinfection. RESULTS: Neutralization assays showed that autologous plasma NAb
      responses to the earliest, and in some cases transmitted/founder, virus were
      delayed and had low to undetectable titers in all three superinfected individuals
      prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were
      detected as early as three months post-seroconversion in non-superinfected
      controls. Early plasma NAbs in all subjects showed limited but variable levels of
      heterologous neutralization breadth. Superinfected individuals also exhibited a
      trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but
      higher gp120-specific plasma IgA binding antibodies. CONCLUSIONS: These data
      suggest that the lack of development of IgG antibodies, as reflected in
      autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary
      infection virus, combined with potentially competing, non-protective IgA
      antibodies, may increase susceptibility to superinfection in the context of
      settings where a single HIV-1 subtype predominates.

PMID- 22995127
TI  - Reno-protective effect of NECA in diabetic nephropathy: implication of IL-18 and
      ICAM-1.
AB  - Diabetic nephropathy (DN) remains the most common cause of end-stage renal
      disease. Although, adenosine acts as a local modulator with a cytoprotective
      function, extracellular adenosine usually disappears quickly due to a rapid
      uptake into adjacent cells. Therefore, we investigated the effect of 5'-(N
      ethylcarboxamido)-adenosine (NECA), a stable, nonselective adenosine receptor
      agonist, on diabetes-induced increases in inflammatory cytokines and adhesion
      molecules. The enhancement of adenosine receptor action by NECA was examined in
      the renal tissues of rats with streptozotocin-induced diabetes. Daily i.p.
      injections of NECA at 0.3 mg/kg/day were given to rats, over a two-week period,
      six weeks after the induction of diabetes. Morphological changes were assessed in
      kidney sections. Oxidative stress was examined by measuring tissue
      malondialdehyde. Gene expression of interleukin (IL)-18, tumor necrosis factor
      (TNF)-alpha and intercellular adhesion molecule (ICAM)-1 was measured by real
      time PCR. Activation of cellular, proapoptotic pathways was demonstrated by
      measuring the activation of c-Jun NH(2)-terminal kinases (JNK)-mitogen-activated
      protein kinase (MAPK). We found that diabetes-induced malondialdehyde formation
      activated the production of IL-18, TNF-alpha and ICAM-1, which, in turn,
      activated pro-apoptotic pathways in diabetic rats. Treatment with NECA protected
      diabetic rats by exerting hypoglycemic and antioxidant effects as well as
      reducing gene expression of proinflammatory cytokines. These effects were
      associated with deactivation of JNK-MAPK. In addition, diabetic rats treated with
      NECA showed mild glomerular effects and vacuolation of tubular epithelium. We can
      conclude that activation of adenosine receptors is a potential therapeutic target
      in DN. NECA acts via multiple mechanisms including: reducing diabetes-induced
      oxidative stress, inhibiting gene expression of IL-18, TNF-alpha and ICAM-1, and
      blocking activation of the JNK-MAPK pathway.

PMID- 22995128
TI  - Rare vertebral metastasis in a case of Hereditary Paraganglioma.
AB  - Paragangliomas are rare tumours with a prevalence of 1/10000 to 1/30000. Tumors
      arising from the paraganglia are characteristically of low malignant potential.
      Vertebral metastases are exceedingly rare, and only isolated case reports have
      described them. The authors present the clinical course of a 47 years-old female
      patient with a familial paraganglioma [PGL] with vertebral metastastization, who
      underwent an intralesional tumor excision and corpectomy. Genetic screening
      demonstrated a new germinal frameshift mutation of the SDHB exon 6 [c.587
      591DelC]. After surgery there was normalization of the analytical parameters and
      imagiologic screening. One year later she presented a new image in the the
      pedicle of T11 on the contralateral side of the surgical incision. She performed
      2 treatments with MIBG and 1 cicle of radiotherapy that made the new lesion
      regress. Currently the patient does not present any clinical or analytical
      evidence of new metastasis.This case outlines the clinical course of a patient
      with a PGL syndrome for whom a rare vertebral metastasis was diagnosed. It
      highlights the importance of identifying patients with germline SDHB mutations,
      as these patients are at a high risk of developing malignant disease.

PMID- 22995129
TI  - Relationship between perceived work ability and productivity loss.
AB  - This paper presents an approach to assessing presenteeism (on-the-job
      productivity loss) that is related to perceived work ability. The aim of this
      explorative research was to find out if perceived work ability could be a robust
      indicator, interchangeable with presenteeism, in Finnish food industry
      organizations. The developed approach was based on existing presenteeism research
      as well as on register and survey data. The approach demonstrates that one step
      downward on the 10-point perceived work ability scale theoretically reduces
      employees' on-the-job productivity by ~5 percentage points. At the company level,
      on-the-job productivity loss was 3.7% (mdn 0), while sickness absence was 5.0%
      (mdn 2.2). The probability of productivity loss among factory workers was
      fourfold compared to women in office work. The developed approach makes it
      possible to assess perceived productivity loss at the level of an individual and
      an organization. Perceived work ability may, in fact, be a robust indicator for
      assessing perceived productivity loss.

PMID- 22995130
TI  - Work time control and mental health of workers working long hours: the role  of
      gender and age.
AB  - The aim of this study was to examine the relationship between work time control
      and mental health in workers working long hours. The study also attempted to show
      how that relationship depended on age and gender. Three hundred and six white
      collar workers doing clerical work for over 8 h daily were diagnosed on work time
      control and mental health with the 28-item General Health Questionnaire. The
      results of an analysis of variance (ANOVA) showed that participants working long
      hours but having high control over their work time had a significantly higher
      level of their mental health with regard to somatic complaints and anxiety and
      marginally higher with regard to social dysfunction than workers with low control
      over their work time. Male and female workers reported different problems with
      their mental health depending on what age (stage of life) they were at. It is
      hypothesized that the work-family conflict, inability to fulfil social
      commitments and poor working conditions can influence those effects.

PMID- 22995131
TI  - Risk factors for health disorders in computer operators in telecom Serbia.
AB  - Computer operators are at risk to develop health disorders related to prolonged
      computer use. We assessed the occupational risk factors for computer-related
      health disorders and evaluated health conditions of 939 Serbian computer
      operators. Musculoskeletal (55.8%), ocular (27.3%) and mental disorders (7.1%)
      were reported most frequently. Risk factors for health disorders, in both male
      and female populations, were age; overtime work; negative working atmosphere;
      awkward posture at work; the presence of vibrations, noise, dust and chemical
      pollution in the workplace. Negative working atmosphere, body mass index > 30,
      total job tenure and duration of exposed employment were risk factors for
      developing health disorders only in males, while smoking was a risk factor only
      in the female population. Our study showed high prevalence of musculoskeletal and
      ocular disorders in Serbian computer operators. More effective preventive
      measures are necessary to improve computer operators' health.

PMID- 22995132
TI  - Methods of estimating the effect of integral motorcycle helmets on physiological
      and psychological performance.
AB  - This article proposes a method for a comprehensive assessment of the effect of
      integral motorcycle helmets on physiological and cognitive responses of
      motorcyclists. To verify the reliability of commonly used tests, we conducted
      experiments with 5 motorcyclists. We recorded changes in physiological parameters
      (heart rate, local skin temperature, core temperature, air temperature, relative
      humidity in the space between the helmet and the surface of the head, and the
      concentration of O(2) and CO(2) under the helmet) and in psychological parameters
      (motorcyclists' reflexes, fatigue, perceptiveness and mood). We also studied
      changes in the motorcyclists' subjective sensation of thermal comfort. The
      results made it possible to identify reliable parameters for assessing the effect
      of integral helmets on performance, i.e., physiological factors (head skin
      temperature, internal temperature and concentration of O(2) and CO(2)  under the
      helmet) and on psychomotor factors (reaction time, attention and vigilance, work
      performance, concentration and a subjective feeling of mood and fatigue).

PMID- 22995133
TI  - A safety assessment approach using safety enablers and results.
AB  - Industrial safety is an important issue in Thailand, and attempts have been made
      to improve safety performance and accident records. This paper examines key
      criteria influencing safety improvement. Exploratory factor analysis confirms 9
      safety criteria, including 5 "enablers" and 4 "results", with a total of 47
      associated attributes. A safety assessment approach is developed, using those 9
      key criteria, to measure an organization's current safety maturity level.
      Organizations can use the assessment approach to plan its safety improvement, and
      progress through to higher maturity levels by focusing on the weakest criteria
      shown in the assessment results with the lowest scores.

PMID- 22995134
TI  - Hazard awareness of construction site dumper drivers.
AB  - In UK's construction industry, site dumpers cause more serious accidents than in
      any other type of construction plant. Previous research has indicated that driver
      behaviour plays a pivotal role in the vast majority of these accidents. Using a
      mental models-based approach, 20 dumper drivers were interviewed with regard to
      the process by which several typical types of accident occurred. It was found
      that drivers were generally well-informed about the hazards of driving dumpers on
      a construction site. However, the findings also exposed some critical knowledge
      gaps, which could increase a driver's chances of an accident. Educational
      material relating to these knowledge deficiencies could easily be prepared and
      incorporated into revised construction information leaflets or driver training
      courses.

PMID- 22995135
TI  - New filtering antimicrobial nonwovens with various carriers for biocides as
      respiratory protective materials against bioaerosol.
AB  - This study evaluated the bioactivity of polypropylene melt-blown filtering
      nonwovens used in respiratory protective devices (RPD) with a biocidal agent
      (alkylammonium microbiocides) on 2 mineral carriers. Two types of carriers were
      tested: a bentonite, with an aluminosilicate base, and a perlite, volcanic glass.
      High biostatic and biocidal effects of modified nonwovens with biocides were
      tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus)
      bacteria. Nonwovens modified with a biocide on a bentonite carrier showed an
      opposite reaction to a biocide on a perlite. The research also showed that 10%
      concentration of a biocidal agent on a perlite carrier was sufficient to inhibit
      the growth of bacteria (100% reduction) placed in the structure of a filtering
      material during normal use of RPD. A comparison of the biological activity of 2
      filtering materials, each containing 10% of a perlite and produced in a
      laboratory and industrial conditions, showed no statistically significant
      differences.

PMID- 22995136
TI  - Effects of range and mode on lifting capability and lifting time.
AB  - This study examined the effects of 3 lifting ranges and 3 lifting modes on
      maximum lifting capability and total lifting time. The results demonstrated that
      the maximum lifting capability for FK (from floor to knuckle height) was greater
      than that for KS (from knuckle height to shoulder height) or FS (from floor to
      shoulder height). Additionally, asymmetric lifting with initial trunk rotation
      decreased maximum lifting capability compared with symmetric lifting or
      asymmetric lifting with final trunk rotation. The difference in total lifting
      time between KS and FS was not significant, while FK increased total lifting time
      by ~20% compared with FS even though the travel distance was 50% shorter.

PMID- 22995137
TI  - Effects of hand posture, breathing type, arm posture and body posture on hand
      errors.
AB  - This study consisted of 2 experiments. Experiment 1 examined the effects of hand
      posture, arm posture and body posture on hand error, while experiment 2 examined
      the effects of hand posture, breathing type and body posture on hand error. This
      study showed that more hand errors occurred in the nondominant hand, extended
      arm, normal breathing and standing compared with errors in the dominant hand,
      flexed arm, inspire-hold and sitting, respectively. This study advised people to
      use their dominant hand, flex their arm, inspire and hold the breath and support
      their body while performing fine manipulation tasks. Finally, hand error varied
      dramatically across the participants, indicating the need to screen individuals
      for fine manual manipulation tasks.

PMID- 22995138
TI  - Reducing kickback of portable combustion chain saws and related injury risks:
      laboratory tests and deductions.
AB  - Portable chain saws are still very dangerous machines. Reduced prices of these
      machines mean they are widely available to people who like DIY (do it yourself)
      and professionals. Kickback of chain saws is extremely dangerous for the
      operator. This paper discusses the results of laboratory investigations of
      combustion chain saws. The tests were conducted on a standardized kickback test
      stand and covered the course of kickback, its energy, angle and duration. The
      results showed that during the contact of a saw chain with wood, the first to
      appear was the process of wood cutting, which absorbed 90-95% of the reduced
      energy of the cutting system. The greater the absorbed energy, the smaller the
      kickback angle. Wood cutting work is particularly influenced by proper chain
      tension, the use of chains with anti-kickback links, guide bars with sliding
      endings and a quickly activated chain brake.

PMID- 22995139
TI  - Health effects associated with shift work in 12-hour shift schedule among Iranian
      petrochemical employees.
AB  - INTRODUCTION: The main purposes of this study were to investigate shift-work
      related health problems in 12-h shift schedule and to identify major factors
      associated with these problems. MATERIALS AND METHODS: This cross-sectional study
      was conducted at 8 petrochemical plants. The study population consisted of 1203
      workers (549 shift and 654 day workers). Data on personal details, the shift
      schedule and adverse health outcomes were collected with a self-administered
      questionnaire. RESULTS: The results showed that health problems in shift workers
      were more prevalent than in day workers; however, the differences were
      significant only in gastrointestinal and musculoskeletal disorders. Logistic
      regression analysis revealed that in addition to shift work, other variables such
      as extended work time, type of employment, second job and job unit were
      associated with health problems. CONCLUSIONS: Working shifts is one important
      variable influencing the health of petrochemical workers. To improve workers'
      health, interventional program should focus on the shift schedule as well as
      other significant aspects of working conditions.

PMID- 22995140
TI  - Effect of video-game experience and position of flight stick controller on
      simulated-flight performance.
AB  - The purpose of this study was to determine the effects of video-game experience
      and flight-stick position on flying performance. The study divided participants
      into 2 groups; center- and side-stick groups, which were further divided into
      high and low level of video-game experience subgroups. The experiment consisted
      of 7 sessions of simulated flying, and in the last session, the flight stick
      controller was switched to the other position. Flight performance was measured in
      terms of the deviation of heading, altitude, and airspeed from their respective
      requirements. Participants with high experience in video games performed
      significantly better (p < .001) than the low-experienced group. Also,
      participants performed significantly better (p < .001) with the center-stick than
      the side-stick. When the side-stick controller was switched to the center-stick
      position, performance scores continued to increase (0.78 %). However, after
      switching from a center- to a side-stick controller, performance scores decreased
      (4.8%).

PMID- 22995141
TI  - Analysis of conditions and organization of work of notebook computer users.
AB  - AIM: The aim of this study was to evaluate working conditions with a notebook
      computer (notebook) as a potential cause of musculoskeletal disorders. MATERIAL
      AND METHODS: The study had 2 stages. The first one was a questionnaire survey
      among 300 notebook users. The next stage was an expert analysis of 53 randomly
      selected workstations. The questionnaire survey included questions about the
      participants, their working conditions, work organization and also duration of
      work with a notebook. RESULTS AND CONCLUSIONS: The results of the research showed
      that most examined operators used a notebook as a basic working tool. The most
      important irregularities included an unadjustable working surface, unadjustable
      height of the seat pan and backrest, unadjustable height and distance between the
      armrests and no additional ergonomic devices (external keyboard, docking station,
      notebook stand or footstool).

PMID- 22995143
TI  - Should the decision-making process of reimbursing medicines be improved?

PMID- 22995144
TI  - Orientation dependence of progressive post-yield behavior of human cortical bone
      in compression.
AB  - Identifying the underlying mechanisms of energy dissipation during post-yield
      deformation of bone is critical in understanding bone fragility fractures.
      However, the orientation-dependence of post-yield properties of bone is still
      poorly understood. Thus, the objective of this study was to determine the effect
      of loading direction on the evolution of post-yield behavior of bone using a
      progressive loading protocol. To do so, cylindrical compressive bone samples were
      prepared each in the longitudinal, circumferential and radial directions, from
      the mid-shaft of cadaveric femurs procured from eight middle-aged male donors
      (51.5 +/- 3.3 years old). These specimens were tested in compression in a
      progressive loading scheme. The results exhibited that the elastic modulus, yield
      stress, and energy dissipation were significantly greater in the longitudinal
      direction than in the transverse (circumferential and radial) directions.
      However, no significant differences were observed in the yield strain as well as
      in the successive plastic strain with respect to the increasing applied strain
      among the three orientations. These results suggest that the initiation and
      progression of plastic strain are independent of loading orientations, thus
      implying that the underlying mechanism of plastic behavior of bone in compression
      is similar in all the orientations.

PMID- 22995145
TI  - Analysis of damped tissue vibrations in time-frequency space: a wavelet-based
      approach.
AB  - There is evidence that vibrations of soft tissue compartments are not
      appropriately described by a single sinusoidal oscillation for certain types of
      locomotion such as running or sprinting. This paper discusses a new method to
      quantify damping of superimposed oscillations using a wavelet-based time
      frequency approach. This wavelet-based method was applied to experimental data in
      order to analyze the decay of the overall power of vibration signals over time.
      Eight healthy subjects performed sprinting trials on a 30 m runway on a hard
      surface and a soft surface. Soft tissue vibrations were quantified from the
      tissue overlaying the muscle belly of the medial gastrocnemius muscle. The new
      methodology determines damping coefficients with an average error of 2.2% based
      on a wavelet scaling factor of 0.7. This was sufficient to detect differences in
      soft tissue compartment damping between the hard and soft surface. On average,
      the hard surface elicited a 7.02 s(-1) lower damping coefficient than the soft
      surface (p<0.05). A power spectral analysis of the muscular vibrations occurring
      during sprinting confirmed that vibrations during dynamic movements cannot be
      represented by a single sinusoidal function. Compared to the traditional
      sinusoidal approach, this newly developed method can quantify vibration damping
      for systems with multiple vibration modes that interfere with one another. This
      new time-frequency analysis may be more appropriate when an acceleration trace
      does not follow a sinusoidal function, as is the case with multiple forms of
      human locomotion.

PMID- 22995142
TI  - Prevalence of amino acid mutations in hepatitis C virus core and NS5B regions
      among Venezuelan viral isolates and comparison with worldwide isolates.
AB  - BACKGROUND: Recent reports show that R70Q and L/C91M amino acid substitutions in
      the core from different hepatitis C virus (HCV) genotypes have been associated
      with variable responses to interferon (IFN) and ribavirin (RBV) therapy, as well
      to an increase of hepatocellular carcinoma (HCC) risk, liver steatosis and
      insulin resistance (IR). Mutations in NS5B have also been associated to IFN, RBV,
      nucleoside and non-nucleoside inhibitors drug resistance. The prevalence of these
      mutations was studied in HCV RNA samples from chronically HCV-infected drug-naive
      patients. METHODS: After amplification of core and NS5B region by nested-PCR, 12
      substitutions were analyzed in 266 Venezuelan HCV isolates subtype 1a, 1b, 2a,
      2c, 2b, 2j (a subtype frequently found in Venezuela) and 3a (n = 127 and n = 228
      for core and NS5B respectively), and compared to isolates from other countries (n
      = 355 and n = 646 for core and NS5B respectively). RESULTS: R70Q and L/C91M core
      substitutions were present exclusively in HCV G1b. Both substitutions were more
      frequent in American isolates compared to Asian ones (69% versus 26%, p < 0.001
      and 75% versus 45%, p < 0.001 respectively). In Venezuelan isolates NS5B D310N
      substitution was detected mainly in G3a (100%) and G1a (13%), this later with a
      significantly higher prevalence than in Brazilian isolates (p = 0.03). The NS5B
      mutations related to IFN/RBV treatment D244N was mainly found in G3a, and Q309R
      was present in all genotypes, except G2. Resistance to new NS5B inhibitors
      (C316N) was only detected in 18% of G1b, with a significantly lower prevalence
      than in Asian isolates, where this polymorphism was surprisingly frequent (p <
      0.001). CONCLUSIONS: Genotypical, geographical and regional differences were
      found in the prevalence of substitutions in HCV core and NS5B proteins. The
      substitutions found in the Venezuelan G2j type were similar to that found in G2a
      and G2c isolates. Our results suggest a high prevalence of the R70Q and L/C91M
      mutations of core protein for G1b and D310N substitution of NS5B protein for the
      G3a. C316N polymorphism related with resistance to new NS5B inhibitors was only
      found in G1b. Some of these mutations could be associated with a worse prognosis
      of the disease in HCV infected patients.

PMID- 22995146
TI  - The mediation of the central histaminergic system in the pressor effect of
      intracerebroventricularly injected melittin, a phospholipase A2 activator, in
      normotensive rats.
AB  - Melittin is a polypeptide component of bee venom that leads to an increase in
      arachidonic acid release and subsequently in prostaglandin synthesis by
      activating phospholipase A(2). Recently we demonstrated that centrally or
      peripherally administrated melittin caused pressor effect and central thromboxane
      A(2) (TXA(2)) and cholinergic system mediated these effects of melittin. Also
      centrally injected histamine leads to pressor and bradycardic response by
      activating central histamine receptors in normotensive rats and central
      cholinergic system involved the effects of histamine. The present study
      demonstrates an involvement of the central histaminergic system in melittin
      induced cardiovascular effect in normotensive rats. Experiments were carried out
      in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin
      (0.5, 1 and 2 nmol) caused dose- and time-dependent increases in mean arterial
      pressure (MAP) and decrease in heart rate (HR) as we reported previously.
      Moreover, H(2) receptor antagonist ranitidine (50 nmol; i.c.v.) almost completely
      and H(3)/H(4) receptor antagonist thioperamide (50 nmol; i.c.v.) partly blocked
      melittin-evoked cardiovascular effects, whereas H(1) receptor blocker
      chlorpheniramine (50 nmol; i.c.v.) had no effect. Also centrally injected
      melittin was accompanied by 28% increase in extracellular histamine concentration
      in the posterior hypothalamus, as shown in microdialysis studies. In conclusion,
      results show that centrally administered melittin causes pressor and bradycardic
      response in conscious rats. Moreover, according to our findings, there is an
      involvement of the central histaminergic system in melittin-induced
      cardiovascular effects.

PMID- 22995147
TI  - Effects of through-hole drug reservoirs on key clinical attributes for drug
      eluting depot stent.
AB  - Atherosclerosis, a condition related to cholesterol build-up and thickening of
      the inner wall of the artery, narrows or occludes the artery lumen. The drug
      eluting stent is a major breakthrough for the treatment of such coronary artery
      diseases. In recent years, another innovative variation of the drug-eluting stent
      with drug reservoirs has been introduced. It allows programmable drug delivery
      with spatial and temporal control and has several potential advantages over
      traditional drug-eluting stents. However, creating such reservoirs on the stent
      struts may weaken the stent scaffolding and compromise its mechanical integrity.
      In this paper, the effects of these micro-sized through-hole drug reservoirs on
      several key clinically relevant functional attributes of the depot stent were
      investigated. Finite element models were developed to predict the mechanical
      integrity of a balloon-expandable stent at various stages such as manufacturing
      and deployment, as well as the stent radial strength and fatigue life. Results
      show that (1) creating drug reservoirs on a stent could impact the stent fatigue
      resistance to some degree; (2) drug reservoirs on the stent crowns led to much
      greater loss in all key clinical attributes than reservoirs on other locations;
      (3) reservoir shape change resulted in little differences in all key clinical
      attributes; (4) for the same drug loading capacity, larger and fewer reservoirs
      yielded lower equivalent plastic strain and radial strength but higher fatigue
      safety factor; and (5) the proposed depot stent was proven to be a feasible
      design. Its total drug capacity could be tripled with acceptable marginal trade
      off in key clinical attributes. These results can serve as the guidelines to help
      future stent designs to achieve the best combination of stent mechanical
      integrity and smart drug delivery in the future, thereby opening up a wide
      variety of new treatment potentials and opportunities.

PMID- 22995148
TI  - An antigenic domain within a catalytically active Leishmania infantum nucleoside
      triphosphate diphosphohydrolase (NTPDase 1) is a target of inhibitory antibodies.
AB  - We identified a shared B domain within nucleoside triphosphate
      diphosphohydrolases (NTPDases) of plants and parasites. Now, an NTPDase activity
      not affected by inhibitors of adenylate kinase and ATPases was detected in
      Leishmania infantum promastigotes. By non-denaturing gel electrophoresis of
      detergent-homogenized promastigote preparation, an active band hydrolyzing
      nucleosides di- and triphosphate was visualized and, following SDS-PAGE and
      silver staining was identified as a single polypeptide of 50kDa. By Western
      blots, it was recognized by immune sera raised against potato apyrase (SA), r-pot
      B domain (SB), a recombinant polypeptide derived from the potato apyrase, and
      LbB1LJ (SC) or LbB2LJ (SD), synthetic peptides derived from the Leishmania
      NTPDase 1, and by serum samples from dogs with visceral leishmaniasis,
      identifying the antigenic L. infantum NTPDase 1 and, also, its conserved B domain
      (r83-122). By immunoprecipitation assays and Western blots, immune sera SA and SB
      identified the catalytically active NTPDase 1 in promastigote preparation. In
      addition, the immune sera SB (44%) and SC or SD (87-99%) inhibited its activity,
      suggesting a direct effect on the B domain. By ELISA, 37%, 45% or 50% of 38
      infected dogs were seropositive for r-pot B domain, LbB1LJ and LbB2LJ,
      respectively, confirming the B domain antigenicity.

PMID- 22995149
TI  - Identification by Q-PCR of Trypanosoma cruzi lineage and determination of blood
      meal sources in triatomine gut samples in Mexico.
AB  - Triatomine vectors were collected on human dwellings in Michoacan Mexico. Blood
      meal sources were identified by real time polymerase chain reaction (Q-PCR) using
      DNA extracted from triatomine guts. The assay was performed with one only
      specific primer set to amplify a fragment of the mitochondrial 12S ribosomal gene
      from vertebrate species. Also Trypanosoma cruzi parasites were detected in
      triatomine gut samples by microscopy and the positive infection was tested in
      mice. In addition T. cruzi discrete taxonomic units (DTUs) were identified by Q
      PCR with two sets of primers that amplify the mini-circle region (miniexon) and
      18S ribosomal mitochondrial gene. The sequences obtained from 18S ribosomal gene
      amplifications confirmed the presence of T. cruzi I and II lineages, and provide
      evidence of the presence of lineage TcIII and TcIV.

PMID- 22995150
TI  - [Contribution of time of flight and point spread function modeling to the
      performance characteristics of the PET/CT Biograph mCT scanner].
AB  - OBJECTIVE: To characterize the performance of the Biograph mCT PET/CT TrueV
      scanner with time of flight (TOF) and point spread function (PSF) modeling.
      MATERIAL AND METHODS: The PET/CT scanner combines a 64-slice CT and PET scanner
      that incorporates in the reconstruction the TOF and PSF information. PET
      operating characteristics were evaluated according to the standard NEMA NU 2
      2007, expanding some tests. In addition, different reconstruction algorithms were
      included, and the intrinsic radiation and tomographic uniformity were also
      evaluated. RESULTS: The spatial resolution (FWHM) at 1 and 10cm was 4.4 and
      5.3mm, improving to 2.6 and 2.5mm when PSF is introduced. Sensitivity was 10.9
      and 10.2 Kcps/MBq at 0 and 10cm from the axis. Scatter fraction was less than 34%
      at low concentrations and the noise equivalent count rate (NECR) was maximal at
      27.8 kBq/mL with 182 Kcps, the intrinsic radiation produced a rate of 4.42 true
      coincidences per second. Coefficient of variation of the volume and system
      uniformity were 4.7 and 0.8% respectively. The image quality test showed better
      results when PSF and TOF were included together. PSF improved the hot spheres
      contrast and background variability, while TOF improved the cold spheres
      contrast. CONCLUSIONS: The Biograph mCT TrueV scanner has good performance
      characteristics. The image quality improves when the information from the PSF and
      the TOF is incorporated in the reconstruction.

PMID- 22995151
TI  - Combined effects of a valgus knee brace and lateral wedge foot orthotic on the
      external knee adduction moment in patients with varus gonarthrosis.
AB  - OBJECTIVE: To test the hypothesis that a custom-fit valgus knee brace and custom
      made lateral wedge foot orthotic will have greatest effects on decreasing the
      external knee adduction moment during gait when used concurrently. DESIGN: Proof
      of-concept, single test session, crossover trial. SETTING: Biomechanics
      laboratory within a tertiary care center. PARTICIPANTS: Patients (n=16) with
      varus alignment and knee osteoarthritis (OA) primarily affecting the medial
      compartment of the tibiofemoral joint (varus gonarthrosis). INTERVENTIONS: Custom
      fit valgus knee brace and custom-made full-length lateral wedge foot orthotic.
      Amounts of valgus angulation and wedge height were tailored to each patient to
      ensure comfort. MAIN OUTCOME MEASURES: The external knee adduction moment (% body
      weight [BW]*height [Ht]), frontal plane lever arm (cm), and ground reaction force
      (N/kg), determined from 3-dimensional gait analysis completed under 4 randomized
      conditions: (1) control (no knee brace, no foot orthotic), (2) knee brace, (3)
      foot orthotic, and (4) knee brace and foot orthotic. RESULTS: The reduction in
      knee adduction moment was greatest when concurrently using the knee brace and
      foot orthotic (effect sizes ranged from 0.3 to 0.4). The mean decrease in first
      peak knee adduction moment compared with control was .36% BW*Ht (95% confidence
      interval [CI], -.66 to -.07). This was accompanied by a mean decrease in frontal
      plane lever arm of .59cm (95% CI, -.94 to -.25). CONCLUSIONS: These findings
      suggest that using a custom-fit knee brace and custom-made foot orthotic
      concurrently can produce a greater overall reduction in the knee adduction
      moment, through combined effects in decreasing the frontal plane lever arm.

PMID- 22995153
TI  - Surgical ophthalmologic examination.
AB  - Maxillofacial trauma involving injury to the eye and periorbital structures is
      not uncommon. Oral and maxillofacial surgeons are frequently called on to assess
      and operate in and around the orbit; it is thus critical to be proficient around
      the eye because surgical interventions and even physical examinations can cause
      injury and loss of vision. This article reviews the systematic and accurate
      assessment of the eye and adnexal structures in a manner appropriate for the oral
      and maxillofacial surgeon, with a focus on proper examination technique and a
      high sensitivity for potentially critical abnormalities. A practical approach to
      performing and recording a detailed ophthalmologic examination is presented,
      including the assessment of vision, pupillary function, intraocular pressure, and
      ocular motility, as well as the slit lamp and direct fundoscopic examinations.

PMID- 22995152
TI  - The standard of healthcare accreditation standards: a review of empirical
      research underpinning their development and impact.
AB  - BACKGROUND: Healthcare accreditation standards are advocated as an important
      means of improving clinical practice and organisational performance. Standard
      development agencies have documented methodologies to promote open, transparent,
      inclusive development processes where standards are developed by members. They
      assert that their methodologies are effective and efficient at producing
      standards appropriate for the health industry. However, the evidence to support
      these claims requires scrutiny. The study's purpose was to examine the empirical
      research that grounds the development methods and application of healthcare
      accreditation standards. METHODS: A multi-method strategy was employed over the
      period March 2010 to August 2011. Five academic health research databases
      (Medline, Psych INFO, Embase, Social work abstracts, and CINAHL) were
      interrogated, the websites of 36 agencies associated with the study topic were
      investigated, and a snowball search was undertaken. Search criteria included
      accreditation research studies, in English, addressing standards and their
      impact. Searching in stage 1 initially selected 9386 abstracts. In stage 2, this
      selection was refined against the inclusion criteria; empirical studies (n =
      2111) were identified and refined to a selection of 140 papers with the exclusion
      of clinical or biomedical and commentary pieces. These were independently
      reviewed by two researchers and reduced to 13 articles that met the study
      criteria. RESULTS: The 13 articles were analysed according to four categories:
      overall findings; standards development; implementation issues; and impact of
      standards. Studies have only occurred in the acute care setting, predominately in
      2003 (n = 5) and 2009 (n = 4), and in the United States (n = 8). A
      multidisciplinary focus (n = 9) and mixed method approach (n = 11) are common
      characteristics. Three interventional studies were identified, with the remaining
      10 studies having research designs to investigate clinical or organisational
      impacts. No study directly examined standards development or other issues
      associated with their progression. Only one study noted implementation issues,
      identifying several enablers and barriers. Standards were reported to improve
      organisational efficiency and staff circumstances. However, the impact on
      clinical quality was mixed, with both improvements and a lack of measurable
      effects recorded. CONCLUSION: Standards are ubiquitous within healthcare and are
      generally considered to be an important means by which to improve clinical
      practice and organisational performance. However, there is a lack of robust
      empirical evidence examining the development, writing, implementation and impacts
      of healthcare accreditation standards.

PMID- 22995154
TI  - Aesthetic surgery of the orbits and eyelids.
AB  - This article discusses the relevant anatomy, the aging process of the eyelid with
      periorbital structure, and how to evaluate patients for a proper surgical
      approach. A description is given of how to achieve an aesthetic balance between
      the forehead, eyelids, and midface to provide the patient with a natural youthful
      appearance. The paradigm in oculoplastic surgery has shifted to more conservative
      eyelid skin, muscle, and fat resection as well as more periorbital soft tissue
      lift, suspension, and volumization. Recent innovations and developments are
      discussed as well as the most common complications in eyelid and periorbital
      surgery.

PMID- 22995155
TI  - IL-1beta a potential factor for discriminating between thyroid carcinoma and
      atrophic thyroiditis.
AB  - Interactions between cytokines and others soluble factors (hormones,
      antibodies...) can play an important role in the development of thyroid
      pathogenesis. The purpose of the present study was to examine the possible
      correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH)
      and auto-antibodies (Tg and TPO), and their usefulness in discriminating between
      different thyroid conditions. In this study, we investigated serum from 115
      patients affected with a variety of thyroid conditions (44 Graves' disease, 17
      Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and
      15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum
      samples were measured simultaneously using a multiplexed human cytokine assay.
      Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed
      that IL-1beta serum concentrations allow the discrimination between atrophic
      thyroiditis and papillary thyroid cancer groups (p = 0.027).

PMID- 22995156
TI  - A polymorphism in metallothionein 1A (MT1A) is associated with cadmium-related
      excretion of urinary beta 2-microglobulin.
AB  - OBJECTIVES: Cadmium (Cd) toxicity of the kidney varies between individuals
      despite similar exposure levels. In humans Cd is mainly bound to metallothioneins
      (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in
      MT genes MT1A and MT2A influence Cd-related kidney damage. METHODS: In a cross
      sectional study N=512 volunteers were selected from three areas in South-Eastern
      China, which to varying degree were Cd-polluted from a smelter (control area
      [median Cd in urine U-Cd=2.67 MUg/L], moderately [U-Cd=4.23 MUg/L] and highly [U
      Cd=9.13 MUg/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were
      measured by graphite-furnace atomic absorption spectrometry. MT1A rs11076161
      (G/A), MT2A rs10636 (G/C) and MT2A rs28366003 (A/G) were determined by Taqman
      assays; urinary N-Acetyl-beta-(D)-Glucosaminidase (UNAG) by spectrometry, and
      urinary beta2-microglobulin (UB2M) by ELISA. RESULTS: Higher B-Cd (natural log
      transformed) with increasing number of MT1A rs11076161 A-alleles was found in the
      highly polluted group (p-value trend=0.033; all p-values adjusted for age, sex,
      and smoking). In a linear model a significant interaction between rs11076161
      genotype and B-Cd was found for UNAG (p=0.001) and UB2M concentrations (p=0.001).
      Carriers of the rs11076161 AA genotype showed steeper slopes for the associations
      between Cd in blood and natural log-transformed UB2M (beta=1.2, 95% CI 0.72-1.6)
      compared to GG carriers (beta=0.30, 95% CI 0.15-0.45). Also for UNAG (natural log
      transformed) carriers of the AA genotype had steeper slopes (beta=0.55, 95% CI
      0.27-0.84) compared to GG carriers (beta=0.018, 95% CI -0.79-0.11). CONCLUSIONS:
      MT1A rs11076161 was associated with B-Cd concentrations and Cd-induced kidney
      toxicity at high exposure levels.

PMID- 22995157
TI  - Elevated blood pressure in cytochrome P4501A1 knockout mice is associated with
      reduced vasodilation to omega-3 polyunsaturated fatty acids.
AB  - In vitro cytochrome P4501A1 (CYP1A1) metabolizes omega-3 polyunsaturated fatty
      acids (n-3 PUFAs); eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      primarily to 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20
      epoxydocosapentaenoic acid (19,20-EDP), respectively. These metabolites have been
      shown to mediate vasodilation via increases in nitric oxide (NO) and activation
      of potassium channels. We hypothesized that genetic deletion of CYP1A1 would
      reduce vasodilatory responses to n-3 PUFAs, but not the metabolites, and increase
      blood pressure (BP) due to decreases in NO. We assessed BP by radiotelemetry in
      CYP1A1 wildtype (WT) and knockout (KO) mice+/-NO synthase (NOS) inhibitor. We
      also assessed vasodilation to acetylcholine (ACh), EPA, DHA, 17,18-EEQ and 19,20
      EDP in aorta and mesenteric arterioles. Further, we assessed vasodilation to an
      NO donor and to DHA+/-inhibitors of potassium channels. CYP1A1 KO mice were
      hypertensive, compared to WT, (mean BP in mmHg, WT 103+/-1, KO 116+/-1,
      n=5/genotype, p<0.05), and exhibited a reduced heart rate (beats per minute, WT
      575+/-5; KO 530+/-7; p<0.05). However, BP responses to NOS inhibition and
      vasorelaxation responses to ACh and an NO donor were normal in CYP1A1 KO mice,
      suggesting that NO bioavailability was not reduced. In contrast, CYP1A1 KO mice
      exhibited significantly attenuated vasorelaxation responses to EPA and DHA in
      both the aorta and mesenteric arterioles, but normal vasorelaxation responses to
      the CYP1A1 metabolites, 17,18-EEQ and 19,20-EDP, and normal responses to
      potassium channel inhibition. Taken together these data suggest that CYP1A1
      metabolizes n-3 PUFAs to vasodilators in vivo and the loss of these vasodilators
      may lead to increases in BP.

PMID- 22995158
TI  - Cadmium-induced oxidative stress and histological damage in the myocardium.
      Effects of a soy-based diet.
AB  - Cd exposure has been associated to an augmented risk for cardiovascular disease.
      We investigated the effects of 15 and 100 ppm of Cd on redox status as well as
      histological changes in the rat heart and the putative protective effect of a soy
      based diet. Male Wistar rats were separated into 6 groups and treated during 60
      days as follows: groups (1), (2) and (3) were fed a casein-based diet; groups
      (4), (5) and (6), a soy-based diet; (1) and (4) were given tap water; (2) and (5)
      tap water containing 15 ppm of Cd2+; and (3) and (6) tap water containing 100 ppm
      of Cd2+. Serum lipid peroxides increased and PON-1 activity decreased in group
      (3). Lipoperoxidation also increased in the heart of all intoxicated groups;
      however protein oxidation only augmented in (3) and reduced glutathione levels
      diminished in (2) and (3). Catalase activity increased in groups (3) and (6)
      while superoxide dismutase activity increased only in (6). Glutathione peroxidase
      activity decreased in groups (3) and (6). Nrf2 expression was higher in groups
      (3) and (6), and MTI expression augmented in (3). Histological examination of the
      heart tissue showed the development of hypertrophic and fusion of cardiomyocytes
      along with foci of myocardial fiber necrosis. The transmission electron
      microscopy analysis showed profound ultra-structural damages. No protection
      against tissue degeneration was observed in animals fed the soy-based diet. Our
      findings indicate that even though the intake of a soy-based diet is capable of
      ameliorating Cd induced oxidative stress, it failed in preventing cardiac damage.

PMID- 22995159
TI  - Propagated fixed-bed mixed-acid fermentation: effect of volatile solid loading
      rate and agitation at near-neutral pH.
AB  - To increase conversion and product concentration, mixed-acid fermentation can use
      a countercurrent strategy where solids and liquids pass in opposite directions
      through a series of fermentors. To limit the requirement for moving solids, this
      study employed a propagated fixed-bed fermentation, where solids were stationary
      and only liquid was transferred. To evaluate the role of agitation, continuous
      mixing was compared with periodic mixing. The periodically mixed fermentation had
      similar conversion, but lower yield and selectivity. Increasing volatile solid
      loading rate from 1.5 to 5.1g non-acid volatile solids/(L(liq).d) and increasing
      liquid retention time decreased yield, conversion, selectivity, but increased
      product concentrations. Compared to a previous study at high pH (~9), this study
      achieved higher performance at near neutral pH (~6.5) and optimal C-N ratios.
      Compared to countercurrent fermentation, propagated fixed-bed fermentations have
      similar selectivities and produce similar proportions of acetic acid, but have
      lower yields, conversion, productivities, and acid concentrations.

PMID- 22995160
TI  - Comparison of nutrient removal capacity and biomass settleability of four high
      potential microalgal species.
AB  - Four common used microalgae species were compared in terms of settleability,
      nutrient removal capacity and biomass productivity. After 1 month training,
      except cyanobacteria Phormidium sp., three green microalgae species,
      Chlamydomonas reinhardtii, Chlorella vulgaris and Scenedesmus rubescens, showed
      good settleability. The N and P removal efficiency was all above 99% within 7, 4,
      6 and 6 days for N and 4, 2, 3 and 4 days for P, resulting in the N removal rates
      of 3.66+/-0.17, 6.39+/-0.20, 4.39+/-0.06 and 4.31+/-0.18 mg N/l/d and P removal
      rates of 0.56+/-0.07, 0.89+/-0.05, 0.76+/-0.09 and 0.60+/-0.05 mg P/l/d for
      Phormidium sp., C. reinhardtii, C. vulgaris and S. rubescens, respectively.
      Phormidium sp. had the lowest algal biomass productivity (2.71+/-0.7 g/m(2)/d)
      and the other three green microalgae showed higher algal biomass productivity
      (around 6 g/m(2)/d). Assimilation into biomass was the main removal mechanism for
      N and P.

PMID- 22995161
TI  - Feasibility of anaerobic co-digestion of pig waste and paper sludge.
AB  - Pig waste (PW) and paper sludge (PS) possess complementary properties that can be
      combined for successful anaerobic digestion. Biochemical methane potential (BMP)
      tests revealed that a PW:PS 3:1 (v/v) ratio had the highest normalized CH(4)-COD
      removal (54%), while PS had the lowest value (11%) and PW had 44%. Batch BMP
      tests revealed a significant decrease in lag times for methane production in the
      order of PW:PS 1:3 (14 days)<PW:PS 1:1 (17 days)<PW:PS 3:1 (20 days)<PW (23
      days). Hydrolysis constants (k(hyd)) were higher for all PW:PS combinations than
      for either of the individual waste streams: 0.004 d(-1) (PS)<0.02 d(-1)
      (PW)<0.024 d(-1) (PW:PS 3:1)<0.03 d(-1) (PW:PS 1:1)<0.05 d(-1) (PW:PS 1:3). Semi
      continuous reactors performing co-digestion of PW and PS at a 2:1 ratio showed
      1.5 times higher methane production than baseline PW-only reactors, confirming
      the BMP results.

PMID- 22995162
TI  - The impact of nitrogen starvation on the dynamics of triacylglycerol accumulation
      in nine microalgae strains.
AB  - Microalgae-derived lipids are an alternative to vegetable and fossil oils, but
      lipid content and quality vary among microalgae strains. Selection of a suitable
      strain for lipid production is therefore of paramount importance. Based on
      published results for 96 species, nine strains were selected to study their
      biomass, total fatty acid, and triacylglycerol (TAG) production under nitrogen
      sufficient and deficient cultivation conditions. Under nitrogen-deficient
      conditions, Chlorella vulgaris, Chlorella zofingiensis, Neochloris oleoabundans,
      and Scenedesmus obliquus, accumulated more than 35% of their dry weight as TAGs.
      Palmitic and oleic acid were the major fatty acids produced. The main difference
      between these strains was the amount of biomass that was produced (3.0-7.8-fold
      increase in dry weight) and the duration that the biomass productivity was
      retained (2-7 days) after nitrogen depletion. S. obliquus (UTEX 393) and C.
      zofingiensis (UTEX B32) showed the highest average TAG productivity (322 and 243
      mg l(-1)day(-1)).

PMID- 22995163
TI  - Combination of struvite pyrolysate recycling with mixed-base technology for
      removing ammonium from fertilizer wastewater.
AB  - Removal of ammonium from wastewater via struvite (MAP) pyrolysate recycling
      combined with a mixed-base NaOH/Mg(OH)(2) technology was investigated, and the
      phosphate and magnesium concentration in the supernatant were measured. The
      optimal parameters for acidolysis were a pH of 1; temperature of 120 degrees C
      and time of 2h. The presence of derivatives of amorphous magnesium hydrogen
      phosphate (MgHPO(4)), namely magnesium phosphate (Mg(3)(PO(4))(2)) and magnesium
      pyrophosphate (Mg(2)P(2)O(7)) were verified by experiment. The ammonium removal
      ratio in this combined mixed-base technology was 96.8% in the first cycle, 80.6%
      in the second, and 81.0% after acidolysis. The phosphate and magnesium ions
      concentration in the supernatant were about 1mg/L and 40 mg/L, respectively. The
      grain size of MAP was 1.52 nm without seeding and 1.79 nm with seeding, and the
      growth rate of MAP was 17.6%.

PMID- 22995164
TI  - Increased production of alkaline polygalacturonate lyase in the recombinant
      Pichia pastoris by controlling cell concentration during continuous culture.
AB  - Recombinant alkaline polygalacturonate lyase (PGL) production by recombinant
      Pichia pastoris GS115 was selected as a model to study as a continuous culture
      strategy for enhancing heterologous protein production based on controlling
      methanol feeding (CCCM culture) or on dual carbon source feeding (CCCD culture).
      Using the CCCM process with a dry cell weight of 75 g/L regulated by controlling
      methanol concentration in the induction media, the final PGL activity was 441.9
      U/mL. The PGL productivity (Q(v)) and the average specific enzyme production rate
      (Q(x)) were 4.65 U mL(-1)h(-1) and 84.5 U g(-1)h(-1), an increase of 42.1% and
      191.2%, respectively, over what was achieved with traditional fed-batch culture
      with high cell density. The control strategies also reduced proteolytic
      degradation by 84.1% in the fermentation broth and increased cell viability by
      12.2%.

PMID- 22995165
TI  - Simultaneous waste activated sludge disintegration and biological hydrogen
      production using an ozone/ultrasound pretreatment.
AB  - This paper offers an effective pretreatment method that can simultaneously
      achieve excess sludge reduction and bio-hydrogen production from sludge self
      fermentation. Batch tests demonstrated that the combinative use of
      ozone/ultrasound pretreatment had an advantage over the individual ozone and
      ultrasound pretreatments. The optimal condition (ozone dose of 0.158 g O(3)/g DS
      and ultrasound energy density of 1.423 W/mL) was recommended by response surface
      methodology. The maximum hydrogen yield was achieved at 9.28 mL H(2)/g DS under
      the optimal condition. According to the kinetic analysis, the highest hydrogen
      production rate (1.84 mL/h) was also obtained using combined pretreatment, which
      well fitted the predicted equation (the squared regression statistic was 0.9969).
      The disintegration degrees (DD) were limited to 19.57% and 46.10% in individual
      ozone and ultrasound pretreatments, while it reached up to 60.88% in combined
      pretreatment. The combined ozone/ultrasound pretreatment provides an ideal and
      environmental friendly solution to the problem of sludge disposal.

PMID- 22995166
TI  - Effective microbes for simultaneous bio-oxidation of ammonia and manganese in
      biological aerated filter system.
AB  - This study determined the most effective microbes acting as ammonia-oxidising
      (AOB) and manganese-oxidising bacteria (MnOB) for the simultaneous removal of
      ammonia (NH(4)(+)-N) and manganese (Mn(2+)) from water. Two conditions of mixed
      culture of bacteria: an acclimatised mixed culture (mixed culture: MC) in a 5-L
      bioreactor and biofilm attached on a plastic medium (stages of mixed culture:
      SMC) in a biological aerated filter were isolated and identified using Biolog
      MicroSystem and 16S rRNA sequencing. A screening test for determining the most
      effective microbe in the removal of NH(4)(+)-N and Mn(2+) was initially performed
      using SMC and MC, respectively, and found that Bacillus cereus was the most
      effective microbe for the removal of NH(4)(+)-N and Mn(2+). Moreover, the
      simultaneous NH(4)(+)-N and Mn(2+) removal (above 95% removal for both NH(4)(+)-N
      and Mn(2+)) was achieved using a biological aerated filter under various
      operating conditions. Thus, the strain could act as an effective microbe of AOB
      and a MnOB for the simultaneous removal of NH(4)(+)-N and Mn(2+).

PMID- 22995167
TI  - Rhizosphere mediated electrogenesis with the function of anode placement for
      harnessing bioenergy through CO2 sequestration.
AB  - The feasibility of power generation by non-destructive usage of rhizodeposits of
      Pennisetum setaceum plant formed mainly due to photosynthesis-carbon
      sequestration mechanism was studied in rhizosphere based microbial fuel-cell (R
      MFC). Four fuel-cell assemblies (non-catalyzed graphite-plates; membrane-less
      operation; air-cathode) were evaluated for their electrogenic activity by varying
      anode distances from root in rhizosphere [A1 - 0; A2 - 8; A3 - 12 and A4 - 16 cm]
      at 2 cm depth from soil-layer and analyzed their electrogenic potential. The fuel
      cell assembly near to the root zone showed maximum electrogenic-activity (R1,
      1007 mV/4.52 mA) followed by R2 (780 mV/4.11 mA), R3 (720 mV/3.4 mA) and R4 (220
      mV/1.2 mA). The observed maximum electrogenesis with R1 and minimum with R4
      electrode-assemblies enumerated the critical role of root-exudates as substrates.
      All fuel-cell assemblies showed 10% higher electrogenic activity during day-time
      operation which can be directly attributed to plant's photosynthetic activity.
      The study enumerated the potential of plant to harness power in a sustainable way
      by optimum placement of fuel-cell setup in their rhizosphere.

PMID- 22995168
TI  - Methyl syringate: an efficient phenolic mediator for bacterial and fungal
      laccases.
AB  - The aim of the present work is to provide insight into the mechanism of laccase
      reactions using syringyl-type mediators. We studied the pH dependence and the
      kinetics of oxidation of syringyl-type phenolics using the low CotA and the high
      redox potential TvL laccases. Additionally, the efficiency of these compounds as
      redox mediators for the oxidation of non-phenolic lignin units was tested at
      different pH values and increasing mediator/non-phenolic ratios. Finally, the
      intermediates and products of reactions were identified by LC-MS and (1)H NMR.
      These approaches allow concluding on the (1) mechanism involved in the oxidation
      of phenolics by bacterial laccases, (2) importance of the chemical nature and
      properties of phenolic mediators, (3) apparent independence of the enzyme's
      properties on the yields of non-phenolics conversion, (4) competitive routes
      involved in the catalytic cycle of the laccase-mediator system with several new C
      O coupling type structures being proposed.

PMID- 22995169
TI  - Comparison of solid-state to liquid anaerobic digestion of lignocellulosic
      feedstocks for biogas production.
AB  - Lignocellulosic biomass feedstocks (switchgrass, corn stover, wheat straw, yard
      waste, leaves, waste paper, maple, and pine) were evaluated for methane
      production under liquid anaerobic digestion (L-AD) and solid-state anaerobic
      digestion (SS-AD). No significant difference in methane yield between L-AD and SS
      AD, except for waste paper and pine, were found. However, the volumetric
      productivity was 2- to 7-fold greater in the SS-AD system compared with the L-AD
      system, except for paper. Methane yields from corn stover, wheat straw, and
      switchgrass were 2-5 times higher than those from yard waste, maple, and pine
      biomass. Waste paper had a methane yield of only 15 L/kg VS caused by souring
      during SS-AD due to organic overloading. Pine also had very low biogas yield of
      17 L/kg VS, indicating the need for pretreatment prior to SS-AD. The findings of
      this study can guide future studies to improve the efficiency and stability of SS
      AD of lignocellulosic biomass.

PMID- 22995170
TI  - Eukaryotic and prokaryotic microbial communities during microalgal biomass
      production.
AB  - Eukaryotic and bacterial communities were characterized and quantified in
      microalgal photobioreactor cultures of freshwater Chlorella vulgaris and marine
      Dunaliella tertiolecta. The microalgae exhibited good growth, whilst both
      cultures contained diverse bacterial communities. Both cultures included
      Proteobacteria and Bacteroidetes, while C. vulgaris cultures also contained
      Actinobacteria. The bacterial genera present in the cultures were different due
      to different growth medium salinities and possibly different extracellular
      products. Bacterial community profiles were relatively stable in D. tertiolecta
      cultures but not in C. vulgaris cultures likely due to presence of ciliates
      (Colpoda sp.) in the latter. The presence of ciliates did not, however, cause
      decrease in total number of C. vulgaris or bacteria during 14 days of
      cultivation. Quantitative PCR (qPCR) reliably showed relative microalgal and
      bacterial cell numbers in the batch cultures with stable microbial communities,
      but was not effective when bacterial communities varied. Raw culture samples were
      successfully used as qPCR templates.

PMID- 22995172
TI  - Molecular characterization and expression of three galactinol synthase genes that
      confer stress tolerance in Salvia miltiorrhiza.
AB  - To adapt to changes in their growing environment, plants express several stress
      responsive genes. For example, the products of galactinol synthase (Gols) genes
      play a key role in regulating the levels of raffinose family oligosaccharides and
      conferring resistance to stress. We cloned and characterized three Gols genes in
      Salvia miltiorrhiza. Their expression followed three distinct patterns. Compared
      with the control, SmGols1 was up-regulated by temperature changes but was
      suppressed by exposure to methyl jasmonate or short-term drought. This gene had
      the greatest abundance of transcripts and was assigned a general function of
      carbon storage. SmGols2 responded to all stress and hormone treatments, and
      transcripts were maintained at a high level. Finally, expression of SmGols3 was
      weaker than the other two genes, but was increased significantly under different
      treatments. Over the experimental period, its expression declined to normal
      levels in response to all treatments except exposure to 100 MUM ABA, long-term
      drought, heat (42  degrees C), or chilling (8  degrees C). Based on our finding
      of cis-elements in the 5' flanking regions, we concluded that these genes seem to
      be regulated by several HSF transcription factors. We also targeted their 90-bp
      conserved sequences and used them for RNA interference analysis. Some were
      knocked down to various extents in our transgenic lines. Fluctuations in their
      malondialdehyde contents under different stress treatments, as well as the rate
      of water loss in transformed plants, suggested that lipid peroxidation was more
      likely to occur in the transgenics than in the control. These results indicate
      that SmGols genes could have a main function in responding to cold or heat.
      Therefore, we believe that it is important to investigate this mechanism for
      tolerance in S. miltiorrhiza and to examine how expression of these SmGols and
      other homologs are influenced by abiotic stresses.

PMID- 22995171
TI  - Nuclear hormone receptors in podocytes.
AB  - Nuclear receptors are a family of ligand-activated, DNA sequence-specific
      transcription factors that regulate various aspects of animal development, cell
      proliferation, differentiation, and homeostasis. The physiological roles of
      nuclear receptors and their ligands have been intensively studied in cancer and
      metabolic syndrome. However, their role in kidney diseases is still evolving,
      despite their ligands being used clinically to treat renal diseases for decades.
      This review will discuss the progress of our understanding of the role of nuclear
      receptors and their ligands in kidney physiology with emphasis on their roles in
      treating glomerular disorders and podocyte injury repair responses.

PMID- 22995173
TI  - Left ventricular thrombus formation after acute myocardial infarction as assessed
      by cardiovascular magnetic resonance imaging.
AB  - INTRODUCTION: Left ventricular (LV) thrombus formation is a feared complication
      of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST
      segment elevated MI patients treated with percutaneous coronary intervention
      (PCI) and compared the diagnostic accuracy of transthoracic echocardiography
      (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the
      course of LV thrombi in the modern era of primary PCI. METHODS: 200 patients with
      primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies
      were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24
      months for assessment of clinical status and adverse events. RESULTS: On CMR at
      baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus
      resolution occurred in 15 patients. Two patients had persistence of LV thrombus
      on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12
      patients. In multivariate analysis, thrombus formation on baseline CMR was
      independently associated with, baseline infarct size (g) (B=0.02, SE=0.02,
      p<0.001). Routine TTE had a sensitivity of 21-24% and a specificity of 95-98%
      compared to CMR for the detection of LV thrombi. Intra- and interobserver
      variation for detection of LV thrombus were lower for CMR (kappa=0.91 and
      kappa=0.96) compared to TTE (kappa=0.74 and kappa=0.53). CONCLUSION: LV thrombus
      still occurs in a substantial amount of patients after PCI-treated MI, especially
      in larger infarct sizes. Routine TTE had a low sensitivity for the detection of
      LV thrombi and the interobserver variation of TTE was large.

PMID- 22995174
TI  - Morphine treatment in early life alters glutamate uptake in the spinal
      synaptosomes of adult rats.
AB  - Morphine exposure during the neonatal period can promote changes in pain
      signaling pathways that can be expressed as an increased nociceptive response in
      adult life. Glutamate is the major excitatory neurotransmitter in primary
      afferent terminals and plays a critical role in normal spinal excitatory synaptic
      transmission. Considering the importance of a better understanding of the
      mechanisms that underlie nociceptive changes throughout the life course, the aim
      of this study was investigate the effects of repeated morphine administration at
      postnatal days 8 (P8) to 14 (P14) on glutamate uptake in spinal synaptosomes at
      P30 and P60. The morphine group showed decreased [3H]-glutamate uptake as
      compared to control groups in both P30 and P60. These findings suggest that
      morphine exposure in early life leads to changes in glutamatergic signaling at
      least until the 60th day of age, which may lead to increased levels of glutamate
      in the spinal synaptic cleft and, consequently, an increased nociceptive response
      in adult life. Thus, this study highlights the importance of conducting research
      in this field to provide a comprehensive knowledge of the long-term effects of
      early-life morphine treatment on nociceptive pathways.

PMID- 22995175
TI  - The interplay of phonology and orthography in visual cognate word recognition: an
      ERP study.
AB  - This study examined the role of phonological and orthographic overlap in the
      recognition of cognate words by recording electrophysiological and behavioral
      data. One hundred and ninety-two words were selected: 96 cognate words listed
      according to their phonological and orthographic overlap vs. 96 noncognate words.
      Twenty-four proficient European Portuguese-English bilinguals performed a silent
      reading task with a masked priming paradigm. The results showed that phonology
      interacts with semantic activation at N400 modulations. Phonological priming
      effects were dependent on the orthographic overlap of cognate words. Thus, the
      distinctive processing of cognate words seems to be due to their cross-linguistic
      similarity, which is consistent with a localist connectionist account on cognate
      representation and processing.

PMID- 22995176
TI  - 20Hz membrane potential oscillations are driven by synaptic inputs in collision
      detecting neurons in the frog optic tectum.
AB  - Although the firing patterns of collision-detecting neurons have been described
      in detail in several species, the mechanisms generating responses in these
      neurons to visual objects on a collision course remain largely unknown. This is
      partly due to the limited number of intracellular recordings from such neurons,
      particularly in vertebrate species. By employing patch recordings in a novel
      integrated frog eye-tectum preparation we tested the hypothesis that OFF retinal
      ganglion cells were driving the responses to visual objects on a collision course
      in the frog optic tectum neurons. We found that the majority (22/26) of neurons
      in layer 6 responding to visual stimuli fitted the definition of eta class
      collision-detectors: they readily responded to a looming stimulus imitating
      collision but not a receding stimulus (spike count difference ~10 times) and the
      spike firing rate peaked after the stimulus visual angle reached a threshold
      value of ~20-45 degrees . In the majority of these neurons (15/22) a slow
      frequency oscillation (f=~20Hz) of the neuronal membrane potential could be
      detected in the responses to a simulated collision stimulus, as well as to
      turning off the lights. Since OFF retinal ganglion cells could produce such
      oscillations, our observations are in agreement with the hypothesis that
      'collision' responses in the frog optic tectum neurons are driven by synaptic
      inputs from OFF retinal ganglion cells.

PMID- 22995177
TI  - STOX1A induces phosphorylation of tau proteins at epitopes hyperphosphorylated in
      Alzheimer's disease.
AB  - Intraneuronal fibrillary tangles are a major hallmark of several
      neurodegenerative diseases including Alzheimer's disease. The major constituents
      of these hallmarks are hyper-phosphorylated tau. In this study we used a neuronal
      cellular model which over-expresses transcription factor STOX1A in combination
      with the longest human tau isoform to test the effect of STOX1A on tau
      phosphorylation. Our results show that STOX1A induces phosphorylation of the
      longest human tau isoform at phospho-epitopes typically found in neurofibrillary
      tangles in Alzheimer's disease. In conclusion, our results show a STOX1A
      dependent effect on tau phosphorylation found in neurodegenerative diseases such
      as Alzheimer's disease.

PMID- 22995178
TI  - Adaptive estimation of EEG for subject-specific reactive band identification and
      improved ERD detection.
AB  - The event-related desynchronization (ERD) is a magnitude decrease phenomenon
      which can be found in electroencephalogram (EEG) mu-rhythm in a certain narrow
      frequency band (reactive band) during different sensorimotor tasks and stimuli.
      The success of ERD detection depends on proper identification of subject specific
      reactive band. An adaptive algorithm band limited multiple Fourier linear
      combiner (BMFLC) is employed in this paper for identification of subject specific
      reactive band for real-time ERD detection. With the time-frequency mapping
      obtained with BMFLC, a procedure is formulated for reactive band identification.
      Improved classification is obtained by applying this method to a standard BCI
      data set compared to traditional ERD detection methods. Study conducted with 8
      subjects drawn from BCI Competition IV data set show a 22% increase in ERD and
      10% improvement in classification with the proposed method compared to standard
      ERD based classification.

PMID- 22995179
TI  - Brain potentials associated with the outcome processing in framing effects.
AB  - Framing effect is a cognitive bias referring to the phenomenon that people
      respond differently to different but objectively equivalent descriptions of the
      same problem. By measuring event-related potentials, the present study aimed to
      investigate the neural mechanisms underlying the framing effect, especially how
      the negative and positive frames influence the outcome processing in our brain.
      Participants were presented directly with outcomes framed either positively in
      terms of lives saved or negatively in terms of lives lost in large and small
      group conditions, and were asked to rate the favorableness of each of them. The
      behavioral results showed that the framing effect occurred in both group size
      conditions, with more favorable evaluations associated with positive framing.
      Compared with outcomes in positive framing condition, a significant feedback
      related negativity (FRN) effect was elicited by outcomes in negative framing
      condition, even though the outcomes in different conditions were objectively
      equivalent. The results are explained in terms of the associative model of
      attribute framing effect which states that attribute framing effect occurs as a
      result of a valence-based associative processing.

PMID- 22995180
TI  - Acupuncture at SI5 attenuates morphine seeking behavior after extinction.
AB  - Our previous studies have shown that acupuncture attenuates morphine self
      administration and sensitization behavior as well as withdrawal signs. The
      present study was designed to investigate the role of acupuncture in the
      reinstatement of morphine seeking. Male Sprague-Dawley rats weighing 270-300 g
      were subjected to intravenous catheterization after food training. The animals
      were trained to self-administer morphine (1.0mg/kg, 3 weeks), followed by
      extinction (1 week). Extinction conditions were introduced by substituting saline
      for morphine. The rats were then tested for reinstatement of morphine self
      administration by a priming injection of morphine (0.25mg/kg). To see whether
      acupuncture can reduce morphine reinstatement, acupuncture was performed at SI5
      or LI5 for 1 min immediately before a morphine injection. To further test the
      involvement of gamma aminobutyric acid (GABA) receptors in acupuncture effects,
      GABA receptor antagonists were injected before acupuncture. In the present
      results, acupuncture at SI5, but not at control acupoint LI5 attenuated the
      reinstatement of morphine seeking behavior, which was blocked by the GABA
      receptor antagonists. It suggests that acupuncture can reduce the reinstatement
      of morphine seeking, possibly due to the mediation of GABA receptor system.

PMID- 22995181
TI  - JAK-STAT pathway modulates the roles of iNOS and COX-2 in the cytoprotection of
      early phase of hydrogen peroxide preconditioning against apoptosis induced by
      oxidative stress.
AB  - Our previous studies have demonstrated that preconditioning with hydrogen
      peroxide (H(2)O(2)) activated the JAK-STAT pathway that played an important role
      in the cytoprotection, and inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) mediated the late phase of cytoprotection induced by
      high concentration of H(2)O(2) after preconditioning. Here we sought to identify
      the downstream targets of the JAK-STAT axis that mediated H(2)O(2)
      preconditioning and the expression of iNOS and COX-2 in the early phase of
      H(2)O(2) preconditioning. It was shown that (1) Preconditioning with H(2)O(2) at
      100 MUmol/L for 90 min in PC12 cells induced significant expression of iNOS and
      COX-2. (2) Pretreatment with the iNOS inhibitor AG (10 MUmol/L) or the COX-2
      inhibitor NS-398 (10 MUmol/L) respectively 20min before H(2)O(2) preconditioning
      not only inhibits the increased expression of iNOS or COX-2 but also abrogates
      the protective effects of H(2)O(2) preconditioning against apoptosis induced by
      oxidative stress. (3) Pretreatment with the JAK inhibitor AG-490 (10 MUmol/L) 20
      min before H(2)O(2) preconditioning obviously inhibits the up-regulation of iNOS
      or COX-2 induced by H(2)O(2) preconditioning. These results suggested that JAK
      STAT pathway modulates the roles of iNOS and COX-2 in the cytoprotection of early
      phase of H(2)O(2) preconditioning.

PMID- 22995182
TI  - The relationship between vocal accuracy and variability to the level of
      compensation to altered auditory feedback.
AB  - Auditory feedback plays an important role in monitoring vocal output and
      determining when adjustments are necessary. In this study a group of untrained
      singers participated in a frequency altered feedback experiment to examine if
      accuracy at matching a note could predict the degree of compensation to auditory
      feedback that was shifted in frequency. Participants were presented with a target
      note and instructed to match the note in pitch and duration. Following the onset
      of the participants' vocalizations their vocal pitch was shifted down one semi
      tone at a random time during their utterance. This altered auditory feedback was
      instantaneously presented back to them through headphones. Results indicated that
      note matching accuracy did not correlate with compensation magnitude, however, a
      significant correlation was found between baseline variability and compensation
      magnitude. These results suggest that individuals with a more stable baseline
      fundamental frequency rely more on feedforward control mechanisms than
      individuals with more variable vocal production. This increased weighting of
      feedforward control means they are less sensitive to mismatches between their
      intended vocal production and auditory feedback.

PMID- 22995183
TI  - Spatiotemporal tuning in mouse primary visual cortex.
AB  - The neural correlates of visual motion perception have historically been studied
      in non-human primates. However, the mouse has recently gained popularity as a
      model for studying vision primarily driven by the hope that the genetic tools
      available in this species may contribute to our understanding of visual
      processing in the cortex. A recent calcium-imaging study on the spatiotemporal
      tuning of mouse striate and extrastriate cortex revealed that neurons in the
      primary visual cortex (V1) were almost never speed tuned, whereas previous
      electrophysiological studies in macaques noted around one quarter of V1 neurons
      appeared to be selective for a particular stimulus speed. We were interested in
      whether this discrepancy was due to methodological or species differences, so we
      measured the spatiotemporal tuning of mouse V1 neurons using standard
      electrophysiological techniques. Using comparable analyses to previous studies of
      speed tuning, our data showed that speed tuning is rare in mouse V1, which
      corroborates earlier studies in mouse and points to a species difference in
      motion processing in early cortex between macaques and other mammals.

PMID- 22995184
TI  - A multi-state spatio-temporal Markov model for categorized incidence of
      meningitis in sub-Saharan Africa.
AB  - Meningococcal meningitis is a major public health problem in the African Belt.
      Despite the obvious seasonality of epidemics, the factors driving them are still
      poorly understood. Here, we provide a first attempt to predict epidemics at the
      spatio-temporal scale required for in-year response, using a purely empirical
      approach. District-level weekly incidence rates for Niger (1986-2007) were
      discretized into latent, alert and epidemic states according to pre-specified
      epidemiological thresholds. We modelled the probabilities of transition between
      states, accounting for seasonality and spatio-temporal dependence. One-week-ahead
      predictions for entering the epidemic state were generated with specificity and
      negative predictive value >99%, sensitivity and positive predictive value >72%.
      On the annual scale, we predict the first entry of a district into the epidemic
      state with sensitivity 65?0%, positive predictive value 49?0%, and an average
      time gained of 4?6 weeks. These results could inform decisions on preparatory
      actions.

PMID- 22995185
TI  - Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike
      protein induces systemic and mucosal immunity without redirection of the virus to
      the brain.
AB  - BACKGROUND: Sublingual (s.l.) administration of soluble protein antigens,
      inactivated viruses, or virus-like particles has been shown to induce broad
      immune responses in mucosal and extra-mucosal tissues. Recombinant replication
      defective adenovirus vectors (rADVs) infect mucosa surface and therefore can
      serve as a mucosal antigen delivery vehicle. In this study we examined whether
      s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute
      respiratory syndrome-associated coronavirus (SARS-CoV) induces protective
      immunity against SARS-CoV and could serve as a safe mucosal route for delivery of
      rADV. RESULTS: Here, we show that s.l. administration of rADV-S induced serum
      SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses
      are comparable to those induced by intranasal (i.n.) administration. In addition,
      s.l. immunization induced antigen-specific CD8+ T cell responses in the lungs
      that are superior to those induced by intramuscular immunization. Importantly,
      unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV
      vector to the olfactory bulb. CONCLUSION: Our study indicates that s.l.
      immunization with rADV-S is safe and effective in induction of a broad spectrum
      of immune responses and presumably protection against infection with SARS-CoV.

PMID- 22995186
TI  - Maturation of the Gag core decreases the stability of retroviral lipid membranes.
AB  - To better understand how detergents disrupt enveloped viruses, we monitored the
      biophysical stability of murine leukemia virus (MLV) virus-like particles (VLPs)
      against a panel of commonly used detergents using real-time biosensor
      measurements. Although exposure to many detergents, such as Triton X-100 and
      Empigen, results in lysis of VLP membranes, VLPs appeared resistant to complete
      membrane lysis by a significant number of detergents, including Tween 20, Tween
      80, Lubrol, and Saponin. VLPs maintained their structural integrity after
      exposure to Tween 20 at concentrations up to 500-fold above its CMC. Remarkably,
      VLPs containing immature cores composed of unprocessed (uncleaved) Gag
      polyprotein were significantly more resistant to detergent lysis than VLPs with
      mature cores. Although the maturity of retroviral Gag is known to influence the
      stability of the protein core structure itself, our studies suggest that the
      maturity of the Gag core also influences the stability of the lipid bilayer
      surrounding the core.

PMID- 22995187
TI  - Use of an in vivo animal model for assessing the role of integrin alpha(6)beta(4)
      and syndecan-1 in early steps in papillomavirus infection.
AB  - Human papillomaviruses (HPV) are small DNA tumor viruses. HPV infection requires
      entry of virions into epithelial host cells that support the viral life cycle.
      Here, we used an in vivo mouse model, in which HPV pseudoviruses (PVs) are scored
      for their ability to transduce reporter genes, to test the role of various
      cellular proteins in entry. We initially investigated the role of integrin
      alpha(6)beta(4) in mediating early steps of HPV infection. Deficiency of integrin
      alpha(6)beta(4) is modestly but significantly suppressed reporter-gene
      transduction by PVs in conditional integrin beta(4) knockout mice. We also
      investigated the role of syndecan 1, a heparin sulfate proteoglycan (HSPG) for
      its role in HPV infection. We did not see a significant reduction in reporter
      gene transduction by PVs in syndecan-1 null mice. This indicates that this HSPG
      is not essential for early steps in HPV infection, but does not discount a need
      of other HSPGs in mediating HPV infection.

PMID- 22995188
TI  - Identification of amino acid residues important for anti-IFN activity of porcine
      reproductive and respiratory syndrome virus non-structural protein 1.
AB  - The non-structural protein 1 (nsp1) of porcine reproductive and respiratory
      syndrome virus is partly responsible for inhibition of type I interferon (IFN)
      response by the infected host. By performing alanine-scanning mutagenesis, we
      have identified amino acid residues in nsp1alpha and nsp1beta (the proteolytic
      products of nsp1) that when substituted with alanine(s) exhibited significant
      relief of IFN-suppression. A mutant virus (16-5A, in which residues 16-20 of
      nsp1beta were substituted with alanines) encoding mutant nsp1beta recovered from
      infectious cDNA clone was shown to be attenuated for growth in vitro and induced
      significantly higher amount of type I IFN transcripts in infected macrophages. In
      infected pigs, the 16-5A virus exhibited reduced growth at early times after
      infection but quickly regained wild type growth properties as a result of
      substitutions within the mutated sequences. The results indicate a strong
      selection pressure towards maintaining the IFN-inhibitory property of the virus
      for successful propagation in pigs.

PMID- 22995189
TI  - Characterization of anti-HIV-1 neutralizing and binding antibodies in chronic HIV
      1 subtype C infection.
AB  - Neutralizing (nAbs) and high affinity binding antibodies may be critical for an
      efficacious HIV-1 vaccine. We characterized virus-specific nAbs and binding
      antibody responses over 21 months in eight HIV-1 subtype C chronically infected
      individuals with heterogeneous rates of disease progression. Autologous nAb
      titers of study exit plasma against study entry viruses were significantly higher
      than contemporaneous responses at study entry (p=0.002) and exit (p=0.01). NAb
      breadth and potencies against subtype C viruses were significantly higher than
      for subtype A (p=0.03 and p=0.01) or B viruses (p=0.03; p=0.05) respectively.
      Gp41-IgG binding affinity was higher than gp120-IgG (p=0.0002). IgG-FcgammaR1
      affinity was significantly higher than FcgammaRIIIa (p<0.005) at study entry and
      FcgammaRIIb (p<0.05) or FcgammaRIIIa (p<0.005) at study exit. Evolving IgG
      binding suggests alteration of immune function mediated by binding antibodies.
      Evolution of nAbs was a potential marker of HIV-1 disease progression.

PMID- 22995191
TI  - Characterization of cellular furin content as a potential factor determining the
      susceptibility of cultured human and animal cells to coronavirus infectious
      bronchitis virus infection.
AB  - In previous studies, the Beaudette strain of coronavirus infectious bronchitis
      virus (IBV) was adapted from chicken embryo to Vero, a monkey kidney cell line,
      by serial propagation for 65 passages. To characterize the susceptibility of
      other human and animal cells to IBV, 15 human and animal cell lines were infected
      with the Vero-adapted IBV and productive infection was observed in four human
      cell lines: H1299, HepG2, Hep3B and Huh7. In other cell lines, the virus cannot
      be propagated beyond passage 5. Interestingly, cellular furin abundance in five
      human cell lines was shown to be strongly correlated with productive IBV
      infection. Cleavage of IBV spike protein by furin may contribute to the
      productive IBV infection in these cells. The findings that IBV could productively
      infect multiple human and animal cells of diverse tissue and organ origins would
      provide a useful system for studying the pathogenesis of coronavirus.

PMID- 22995190
TI  - Identification and characterization of RNA duplex unwinding and ATPase activities
      of an alphatetravirus superfamily 1 helicase.
AB  - Dendrolimus punctatus tetravirus (DpTV) belongs to the genus omegatetravirus of
      the Alphatetraviridae family. Sequence analysis predicts that DpTV replicase
      contains a putative helicase domain (Hel). However, the helicase activity in
      alphatetraviruses has never been formally determined. In this study, we
      determined that DpTV Hel is a functional RNA helicase belonging to superfamily-1
      helicase with 5'-3' dsRNA unwinding directionality. Further characterization
      determined the length requirement of the 5' single-stranded tail on the RNA
      template and the optimal reaction conditions for the unwinding activity of DpTV
      Hel. Moreover, DpTV Hel also contains NTPase activity. The ATPase activity of
      DpTV Hel could be significantly stimulated by dsRNA, and dsRNA could partially
      rescue the ATPase activity abolishment caused by mutations. Our study is the
      first to identify an alphatetravirus RNA helicase and further characterize its
      dsRNA unwinding and NTPase activities in detail and should foster our
      understanding of DpTV and other alphatetraviruses.

PMID- 22995192
TI  - Beyond the shadow: getting past the veil of nonadherence in the management of
      atherosclerotic risk factors.

PMID- 22995193
TI  - Synergistic effect of field enhanced sample injection on micelle to solvent
      stacking in capillary electrophoresis.
AB  - Injection of a sodium dodecyl sulfate micellar plug prior to the sample solution
      induced transient micellar phase extraction of cationic drugs in capillary
      electrophoresis. Micelle to solvent stacking mechanism was utilized by preparing
      the sample in aqueous organic solvent. Synergism was achieved with field enhanced
      sample injection that allowed larger sample loads. Micelle to solvent stacking
      occurred concurrently with the enhanced injection after the fast moving analytes
      electrophoretically migrated into the micellar plug. This was different from
      stacking combinations with field enhancement where the electric field strength
      difference was involved in analyte focusing. Using a sample diluent that had one
      tenth the conductivity of the background solution, the strategy afforded
      thousands-fold improvements in peak height and LODs (S/N=3) of as low as 1.1
      ng/mL. The results were repeatable and linear. Adaptability to real sample
      analysis was evaluated using spiked urine sample after minimal sample clean-up.

PMID- 22995194
TI  - A miniaturized method for estimating di(2-ethylhexyl) phthalate in bivalves as
      bioindicators.
AB  - This work has developed a miniaturized method based on matrix solid phase
      dispersion (MSPD), using C18 as dispersant and acetonitrile-water as eluting
      solvent, for the analysis of di(2-ethylhexyl) phthalate (DEHP) in biota samples
      by capillary liquid chromatography coupled to in-tube solid phase microextraction
      and diode array detection. Recovery studies showed that the combination of C18
      Florisil(r) was optimal using low amount of samples (0.1 g) and with low volumes
      of acetonitrile-water (2.6 mL 1:3.25, v/v). The sample is processed in less than
      30 min, no evaporation step is required. The proposed method was applied to the
      analysis of DEHP in mussels and of the coastal waters in which they live. The
      average value of recoveries obtained, with ten spikes realized before MSPD
      treatment and after, was 91+/-15%. The detection limit achieved in mussels was
      170 MUg/kg. Bioconcentration factor values (BCFs) have been discussed, because
      DEHP can be bioconcentrated in aquatic organisms.

PMID- 22995195
TI  - Determination of alkane/water partition coefficients of polar compounds using
      hydrophilic interaction chromatography.
AB  - In this study, the retention factors (logk) of 44 polar neutral compounds were
      measured using hydrophilic interaction chromatography (HILIC). This retention
      parameter was compared with experimental logPalk obtained by a traditional method
      (shake-flask) or with the calculated logPalk for the most hydrophilic compounds.
      A good correlation was obtained between logk90 (measured with a mobile phase
      containing 90% acetonitrile) and logPalk. In contrast, no correlation was
      obtained between the retention factor and logPoct. This method could thus
      represent an advantageous alternative and reliable method to characterise the
      lipophilicity of polar compounds in an alkane/water system by chromatography,
      providing an important insight in (Q)SAR studies to predict drug permeation
      through numerous biorelevant membranes.

PMID- 22995196
TI  - High temperature liquid chromatography-inductively coupled plasma mass
      spectrometry for the determination of arsenosugars in biological samples.
AB  - The potential of high temperature liquid chromatography (HTLC) with detection by
      inductively coupled plasma mass spectrometry (ICP-MS) for the determination of
      arsenosugars in marine organisms was examined for the first time. The retention
      behavior of four naturally occurring dimethylarsinoylribosides was studied on a
      graphite column using plain water as mobile phase. An aqueous solution of pH 8,
      ionic strength 13.8mM and containing 2% (v/v) of methanol, along with a column
      temperature of 120 degrees C and a liquid flow rate of 1.0 mL/min, were selected
      as the optimal conditions, as they allowed the separation of the four
      arsenosugars in less than 18 min, without any interferences due to other common
      arsenic species (arsenite, arsenate, dimethylarsinate, methylarsonate and
      arsenobetaine). The run time could be further decreased to 12 min by working at
      1.5 mL/min, although with a 3-4 times loss of sensitivity. The procedural limits
      of detection were 0.03-0.04 MUg As/g dry mass, and the precision of the procedure
      ranged from 4% for arsenosugar glycerol to 18% for arsenosugar sulfate (RSD%,
      n=5). The developed method was applied to a number of representative biological
      samples, such as algae and crustaceans, providing results consistent with
      previous studies. In the red algae samples, the most of extracted arsenic was as
      arsenosugars (81-97%), mainly arsenosugar phosphate (56-94%). On the other hand,
      lower concentrations of these compounds were found in the crustacean, accounting
      for about 15% of the extracted arsenic.

PMID- 22995197
TI  - Microfluidic chips with reversed-phase monoliths for solid phase extraction and
      on-chip labeling.
AB  - The integration of sample preparation methods into microfluidic devices provides
      automation necessary for achieving complete micro total analysis systems. We have
      developed a technique that combines on-chip sample enrichment with fluorescence
      labeling and purification. Polymer monoliths made from butyl methacrylate were
      fabricated in cyclic olefin copolymer microdevices and used for solid phase
      extraction. We studied the retention of fluorophores, amino acids and proteins on
      these columns. The retained samples were subsequently labeled with both Alexa
      Fluor 488 and Chromeo P503, and unreacted dye was rinsed off the column before
      sample elution. Additional purification was obtained from the differential
      retention of proteins and fluorescent labels. A linear relation between the
      eluted peak areas and concentrations of on-chip labeled heat shock protein 90
      samples demonstrated the utility of this method for on-chip quantitation. Our
      fast and simple method of simultaneously concentrating and labeling samples on
      chip is compatible with miniaturization and desirable for automated analysis.

PMID- 22995198
TI  - Percutaneous intervention on anomalous circumflex coronary arteries--a single
      centre experience.
AB  - BACKGROUND: Anomalies of the origin and course of the circumflex artery are
      amongst the most common seen at coronary angiography. There is limited
      information regarding patient and procedural characteristics, technical
      feasibility and outcomes associated with percutaneous intervention (PCI) to these
      vessels. The aim of this study is to examine our experience with PCI to anomalous
      circumflex vessels and compare this to some aspects of percutaneous intervention
      on non-anomalous circumflex vessels. METHODS: Over a 41 month period, 20 PCI
      procedures on anomalous circumflex vessels were identified and 1550 PCI
      procedures on non-anomalous circumflex arteries. RESULTS: In 9 anomalous cases,
      the circumflex arose from the left coronary cusp, in 7 cases from the right
      coronary cusp, and in the remaining 4 cases from the proximal right coronary
      artery. There were no differences in demographics or pattern or severity of
      coronary disease between the 2 groups. A higher proportion of patients with
      anomalous vessels presented acutely. Screening times were longer in the anomalous
      group. All 20 procedures were associated with immediate procedural success. There
      was one peri-procedural myocardial infarction unrelated to anomalous circumflex
      intervention. After a median follow-up period of 7.3 months, the only major
      adverse cardiac event recorded in the anomalous group was an ischaemia-driven
      revascularisation to a non-target vessel branch. We describe techniques which can
      be used to improve support and facilitate successful PCI to anomalous circumflex
      vessels. CONCLUSION: PCI to anomalous circumflex vessels may be technically
      challenging, but is feasible and carries favourable short and long-term clinical
      outcomes. SUMMARY: This single centre observational study demonstrates that
      percutaneous coronary intervention to anomalous circumflex coronary arteries
      although technically challenging can be performed with satisfactory procedural
      success rates and favourable short and longer-term clinical outcomes. It
      describes various techniques that can be employed to optimise successful
      intervention.

PMID- 22995199
TI  - Auditory nerve function following cochleitis.
AB  - We present a case of temporary cochlear nerve dysfunction due to endocochlear
      inflammation with subsequent recovery. Retrospective case review at a pediatric
      tertiary care hospital. A nine-year-old male presented seven years post-cochlear
      implantation with an electrode array extruded into the external auditory canal.
      Upon exploration in the operating room, turbid perilymph from the scala tympani
      was discovered. A new electrode array was implanted. The patient had no
      discernible neural response telemetry (NRT) responses or auditory perception
      immediately following the procedure. Continuous but varying stimulation was
      continued postoperatively. Two months after implantation, he began having some
      auditory awareness; subsequent mapping resulted in the activation of a limited
      number of channels. Nine months following reimplantation, NRT demonstrated
      responses in three channels. Additionally, functional gain testing revealed sound
      awareness levels in the mild-hearing-loss range and the patient was able to
      detect and repeat all six Ling sounds. Continuous cochlear nerve stimulation at
      various levels may aid in function recovery after endocochlear inflammation.

PMID- 22995200
TI  - Quantification of LLAEP interhemispheric symmetry by the intraclass correlation
      coefficient as a measure of cortical reorganization after cochlear implantation.
AB  - OBJECTIVE: Electrical stimulation by a cochlear implant (CI) induces maturation
      of the auditory system and reorganization of the auditory cortex in deaf
      children. Cortical reorganization produces an interhemispheric asymmetry in
      auditory evoked brain potentials associated with sound stimulation after
      unilateral implantation. To objectively determine the onset of this phenomenon
      and follow this process over time, the interhemispheric symmetry needs to be
      quantified. In this paper, the intraclass correlation coefficient (ICC) between
      mean global field powers (MGFPs) of each hemisphere is proposed to quantify long
      latency auditory evoked potential (LLAEP) interhemispheric symmetries as a
      measure of auditory cortex reorganization in CI recipients. DESIGN: An LLAEP, in
      response to a simple tone, was recorded in 5 juvenile unilateral CI recipients at
      less and at more than two years post-implantation and the ICC between MGFPs was
      calculated for both recordings. The cross correlation coefficients (CC) between
      MGFPs of each hemisphere were also calculated and compared with the ICC. RESULTS:
      The experience-related visually observed increases in amplitude and shape
      asymmetries of the LLAEP topographic map (around the LLAEP P(1) peak), were
      reflected in a considerable reduction of ICC values (on average 41.4%), at more
      than two years post-implantation surgery. In contrast, CC values only showed much
      smaller decreases (on average 20.0%), at more than two years post-implantation.
      CONCLUSIONS: The ICC is a better descriptor of symmetry than the CC because it
      reflects both shape and amplitude similarity between left and right LLAEP MGFPs
      instead of only shape similarity. The decrease in ICC values at more than two
      years post-implantation is likely associated with a lateralization of the
      auditory response as a result of cortical reorganization. Our results show that
      the ICC between the MGFPs for each hemisphere can be useful to objectively
      determine the auditory cortex reorganization process and also to evaluate the
      performance of cochlear implant users without the necessity to use expensive
      technologies such as high density EEG recordings and/or fMRI scans.

PMID- 22995201
TI  - Multilevel airway obstruction including rare tongue base mass presenting as
      severe croup in an infant.
AB  - Laryngomalacia is the most common cause of neonatal stridor, accounting for up to
      60% of cases [1]. Less common causes of neonatal stridor include subglottic or
      tracheal stenosis, or congenital masses of the upper airway. Neonates with an
      identified congenital etiology of symptomatic upper airway obstruction often have
      synchronous airway lesions leading to multilevel airway obstruction. These
      infants deserve an endoscopic evaluation to better diagnose and manage
      respiratory distress. Here we present a rare case of an infant initially
      diagnosed with croup, but ultimately found to have multilevel airway obstruction
      including severe laryngomalacia and an obstructing tongue base mass.

PMID- 22995202
TI  - Genetic modification of lymphocytes by retrovirus-based vectors.
AB  - The genetic modification of lymphocytes is an important topic in the emerging
      field of gene therapy. Many clinical trials targeting immunodeficiency syndromes
      or cancer have shown therapeutic benefit; further applications address
      inflammatory and infectious disorders. Retroviral vector development requires a
      detailed understanding of the interactions with the host. Most researchers have
      used simple gammaretroviral vectors to modify lymphocytes, either directly or via
      hematopoietic stem and progenitor cells. Lentiviral, spumaviral (foamyviral) and
      alpharetroviral vectors were designed to reduce the necessity for cell
      stimulation and to utilize potentially safer integration properties. Novel
      surface modifications (pseudotyping) and transgenes, built using synthetic
      components, expand the retroviral toolbox, altogether promising increased
      specificity and potency. Product consistency will be an important criterion for
      routine clinical use.

PMID- 22995204
TI  - Determination of cadmium(II), cobalt(II), nickel(II), lead(II), zinc(II), and
      copper(II) in water samples using dual-cloud point extraction and inductively
      coupled plasma emission spectrometry.
AB  - A dual-cloud point extraction (d-CPE) procedure has been developed for
      simultaneous pre-concentration and separation of heavy metal ions (Cd2+, Co2+,
      Ni2+, Pb2+, Zn2+, and Cu2+ ion) in water samples by inductively coupled plasma
      optical emission spectrometry (ICP-OES). The procedure is based on forming
      complexes of metal ion with 8-hydroxyquinoline (8-HQ) into the as-formed Triton X
      114 surfactant rich phase. Instead of direct injection or analysis, the
      surfactant rich phase containing the complexes was treated by nitric acid, and
      the detected ions were back extracted again into aqueous phase at the second
      cloud point extraction stage, and finally determined by ICP-OES. Under the
      optimum conditions (pH=7.0, Triton X-114=0.05% (w/v), 8-HQ=2.0*10(-4) mol L(-1),
      HNO3=0.8 mol L(-1)), the detection limits for Cd2+, Co2+, Ni2+, Pb2+, Zn2+, and
      Cu2+ ions were 0.01, 0.04, 0.01, 0.34, 0.05, and 0.04 MUg L(-1), respectively.
      Relative standard deviation (RSD) values for 10 replicates at 100 MUg L(-1) were
      lower than 6.0%. The proposed method could be successfully applied to the
      determination of Cd2+, Co2+, Ni2+, Pb2+, Zn2+, and Cu2+ ion in water samples.

PMID- 22995203
TI  - User involvement in service delivery predicts outcomes of assistive technology
      use: a cross-sectional study in Bangladesh.
AB  - BACKGROUND: Knowledge about the relation between user involvement in the
      provision of assistive technology and outcomes of assistive technology use is a
      prerequisite for the development of efficient service delivery strategies.
      However, current knowledge is limited, particularly from low-income countries
      where affordability is an issue. The objective was therefore to explore the
      relation between outcomes of assistive technology use and user involvement in the
      service delivery process in Bangladesh. METHODS: Using structured interviews,
      data from 136 users of hearing aids and 149 users of manual wheelchairs were
      collected. Outcomes were measured using the International Outcome Inventory for
      Hearing Aids (IOI-HA), which was adapted for wheelchair users. Predictors of user
      involvement included preference, measurement and training. RESULTS: Users
      reported outcomes comparable to those found in other high- and low-income
      countries. User involvement increased the likelihood for reporting better
      outcomes except for measurement among hearing aid users. CONCLUSIONS: The
      findings support the provision of assistive technology as a strategy to improve
      the participation of people with disabilities in society. They also support
      current policies and guidelines for user-involvement in the service delivery
      process. Simplified strategies for provision of hearing aids may be explored.

PMID- 22995205
TI  - Transcriptome profiling of genes differentially modulated by sulfur and chromium
      identifies potential targets for phytoremediation and reveals a complex S-Cr
      interplay on sulfate transport regulation in B. juncea.
AB  - A differential display cDNA-AFLP derived technique was used to identify gene
      transcripts regulated by chromium (Cr) in relation to sulfur (S) nutrition in
      Brassica juncea. Twelve-day old plants were grown with 200 MUM sulfate (+S),
      without sulfate (-S), with 200 MUM sulfate plus 200 MUM chromate (+S+Cr), or
      without sulfate plus 200 MUM chromate (-S+Cr). Forty-four combinations of
      degenerate primers were assayed, which allowed the detection of 346 Transcript
      Derived Fragments (TDFs) differentially regulated by Cr and S at times 0, 10 min,
      1 h, 24 h. Eight sulfate transporters were identified, whose transcript abundance
      was dependent on the levels of plant S-compounds. For some of these transporters,
      a tight coordinated regulation of gene expression was observed in response to Cr.
      The MapMan analysis revealed a differential pattern of gene expression between
      +S+Cr and -S+Cr plants for several other transcripts and highlighted an overlap
      among responses to metals, defence against pathogens and senescence, hence
      suggesting the existence of common mechanisms of gene regulation. Among the
      identified gene transcripts, those involved in S metabolism and proteolitic
      processes may represent potential targets of genetic engineering in efforts to
      increase Cr accumulation and tolerance in plant species employed in
      phytoremediation techniques.

PMID- 22995206
TI  - Enhanced capture of elemental mercury by bamboo-based sorbents.
AB  - To develop cost-effective sorbent for gas-phase elemental mercury removal, the
      bamboo charcoal (BC) produced from renewable bamboo and KI modified BC (BC-I)
      were used for elemental mercury removal. The effect of NO, SO2 on gas-phase Hg0
      adsorption by KI modified BC was evaluated on a fixed bed reactor using an online
      mercury analyzer. BET surface area analysis, temperature programmed desorption
      (TPD) and X-ray photoelectron spectroscopy (XPS) were used to determine the pore
      structure and surface chemistry of the sorbents. The results show that KI
      impregnation reduced the sorbents' BET surface area and total pore volume
      compared with that of the original BC. But the BC-I has excellent adsorption
      capacity for elemental mercury at a relatively higher temperature of 140  degrees
      C and 180  degrees C. The presence of NO or SO2 could inhibit Hg0 capture, but BC
      I has strong anti-poisoning ability. The specific reaction mechanism has been
      further analyzed.

PMID- 22995207
TI  - Intra-uterine growth retardation affects birthweight and postnatal development in
      pigs, impairing muscle accretion, duodenal mucosa morphology and carcass traits.
AB  - The present study investigated the occurrence of intra-uterine growth retardation
      (IUGR) in newborn (n=40) and 150-day-old (n=240) pigs of different birthweight
      ranges (high, HW: 1.8-2.2kg; low, LW: 0.8-1.2kg) from higher-parity commercial
      sows and its impact on their subsequent development and carcass traits in a
      Brazilian commercial production system. HW newborn pigs had heavier organs than
      LW pigs (P<0.01), and all brain:organ weight ratios were higher (P<0.01) in LW
      compared with HW offspring, providing strong evidence of IUGR in the LW piglets.
      HW pigs had higher bodyweights and average daily gain (ADG) in all phases of
      production (P<0.05), but ADG in the finisher phase was similar in both groups.
      Additionally, LW newborn and 150-day-old pigs showed a lower percentage of muscle
      fibres and a higher percentage of connective tissue in the semitendinosus muscle,
      greater fibre number per mm(2) and a lower height of the duodenal mucosa
      (P<0.05). On the other hand, HW pigs had higher hot carcass weight, meat content
      in the carcass and yield of ham, shoulder and belly (P<0.01). Hence, lower
      birthweight piglets may suffer from IUGR, which impairs their growth performance,
      muscle accretion, duodenal mucosa morphology and carcass traits.

PMID- 22995208
TI  - Interface design principles for usable decision support: a targeted review of
      best practices for clinical prescribing interventions.
AB  - Developing effective clinical decision support (CDS) systems for the highly
      complex and dynamic domain of clinical medicine is a serious challenge for
      designers. Poor usability is one of the core barriers to adoption and a deterrent
      to its routine use. We reviewed reports describing system implementation efforts
      and collected best available design conventions, procedures, practices and
      lessons learned in order to provide developers a short compendium of design goals
      and recommended principles. This targeted review is focused on CDS related to
      medication prescribing. Published reports suggest that important principles
      include consistency of design concepts across networked systems, use of
      appropriate visual representation of clinical data, use of controlled
      terminology, presenting advice at the time and place of decision making and
      matching the most appropriate CDS interventions to clinical goals. Specificity
      and contextual relevance can be increased by periodic review of trigger rules,
      analysis of performance logs and maintenance of accurate allergy, problem and
      medication lists in health records in order to help avoid excessive alerting.
      Developers need to adopt design practices that include user-centered, iterative
      design and common standards based on human-computer interaction (HCI) research
      methods rooted in ethnography and cognitive science. Suggestions outlined in this
      report may help clarify the goals of optimal CDS design but larger national
      initiatives are needed for systematic application of human factors in health
      information technology (HIT) development. Appropriate design strategies are
      essential for developing meaningful decision support systems that meet the grand
      challenges of high-quality healthcare.

PMID- 22995209
TI  - Cytokine profiles in serum of patients with oral lichen planus.
AB  - OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disorder of oral
      mucosa, which represents T-cell-mediated autoimmune diseases. The inflammatory
      response in OLP is characterized by the accumulation and expansion of T-helper 1
      (Th1) lymphocytes. Several lines of evidence have suggested that a complex
      cytokine network plays an important role in the exacerbation and perpetuation of
      OLP. The aim of this study was to evaluate Th1 and T-helper 2 (Th2) cytokine
      profile in serum of patients with OLP in comparison to healthy controls. METHODS:
      Thirty patients with OLP, and 30 healthy controls participated in the study.
      Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL
      4, IL-5 and IL-10 levels have been measured in flow cytometry by bead based
      cytokine measurement. RESULTS: Although no statistical differences were observed
      in the serum levels of TNF-alpha, IFN-gamma, IL-5 and IL-4 between OLP patients
      and controls (p>0.05), there were statistically significant differences in the
      serum levels of IL-2 and IL-10 (p<0.05 and p<0.01, respectively). A significantly
      decreased tendency towards the levels of IL-2 were observed in OLP patients when
      compared to controls (p<0.05), and the mean level of IL-10 in serum increased
      remarkably in the OLP patients than those in the controls (p<0.01). CONCLUSIONS:
      The finding of higher serum levels of IL-10 in patients in presence of low serum
      IL-2 levels, shows us that there is a dominance of Th2 response. This makes us
      think that there is a change in Th1/Th2 balance. Dominance of the Th2 response
      may indicate that OLP could be a result of a delayed type hypersensitivity.

PMID- 22995211
TI  - Milestones and future prospects in snake venom research.

PMID- 22995210
TI  - Expression of interferon-gamma, interferon-alpha and related genes in individuals
      with Down syndrome and periodontitis.
AB  - BACKGROUND: Recently, attenuation of anti-inflammatory and increase of pro
      inflammatory mediators was demonstrated in individuals with Down syndrome (DS) in
      comparison with euploid patients during periodontal disease (PD), suggesting a
      shift to a more aggressive inflammation in DS. AIM: To determine the influence of
      DS in the modulation of interferons (IFNs) signaling pathway in PD. MATERIALS AND
      METHODS: Clinical periodontal assessment was performed and gingival tissue
      samples obtained from a total of 51 subjects, including 19 DS individuals with
      PD, 20 euploid individuals with PD and 12 euploid individuals without PD.
      Expression levels of interferon-gamma (IFNG) and interferon-alpha (IFNA), and
      their receptors IFNGR1, IFNGR2, IFNAR1 and IFNAR2, the signaling intermediates
      Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1)
      and interferon regulatory factor 1 (IRF1) were determined using real time
      quantitative polymerase chain reaction (qPCR). RESULTS: Clinical signs of
      periodontal disease were markedly more severe in DS and euploid patients with PD
      in comparison to euploid and periodontally healthy patients. There was no
      difference on mRNA levels of IFNA, IFNG, INFGR2, IFNAR1 and IFNAR2 between DS and
      euploid individuals, even though some of these genes are located on chromosome
      21. STAT1 and IRF1 mRNA levels were significantly lower in DS patients in
      comparison with euploid individuals with PD. In euploid individuals, PD was
      associated with an increased expression of IFNGR1, IFNGR2, IFNAR1, STAT1 and
      IRF1. CONCLUSIONS: Reduced expression of STAT1 and IRF1 genes indicate an
      impaired activation of IFNs signaling in individuals with DS and PD. Expression
      of IFNA, IFNG and IFN receptors was not altered in DS patients, indicating that
      indirect mechanisms are involved in the reduced activation of IFN signaling.

PMID- 22995212
TI  - Effects of a high-calcium diet on serum insulin-like growth factor-1 levels in
      magnesium-deficient rats.
AB  - In order to clarify the effects of a high-calcium (Ca) diet on bone formation in
      magnesium (Mg)-deficient rats, this study focused on the effects of a high-Ca
      diet on serum insulin-like growth factor-1 (IGF-1) levels. Male rats were
      randomized by weight into four groups, and fed one of four experimental diets
      containing two different Mg concentrations (0.05% (normal-Mg) or Mg-free (Mg
      deficient)), and two different Ca concentrations (0.5% (normal-Ca) or 1.0% (high
      Ca)) for 14 days. Serum concentrations of osteocalcin and IGF-1 were
      significantly lower in rats fed the Mg-deficient diet than in rats fed the normal
      Mg diet. On the other hand, dietary Ca concentration had no significant influence
      on serum concentrations of osteocalcin and IGF-1. This study suggested that: 1) a
      high-Ca diet has no preventive effects on the decreased bone formation seen in Mg
      deficient rats; and 2) a high-Ca diet does not enhance serum IGF-1 levels in Mg
      deficient rats. Moreover, unchanged serum IGF-1 concentrations may contribute to
      the decreased bone formation seen in Mg-deficient rats receiving a high-Ca diet.

PMID- 22995214
TI  - DNA double-strand break response in stem cells: mechanisms to maintain genomic
      integrity.
AB  - BACKGROUND: Embryonic stem cells (ESCs) represent the point of origin of all
      cells in a given organism and must protect their genomes from both endogenous and
      exogenous genotoxic stress. DNA double-strand breaks (DSBs) are one of the most
      lethal forms of damage, and failure to adequately repair DSBs would not only
      compromise the ability of SCs to self-renew and differentiate, but will also lead
      to genomic instability and disease. SCOPE OF REVIEW: Herein, we describe the
      mechanisms by which ESCs respond to DSB-inducing agents such as reactive oxygen
      species (ROS) and ionizing radiation, compared to somatic cells. We will also
      discuss whether the DSB response is fully reprogrammed in induced pluripotent
      stem cells (iPSCs) and the role of the DNA damage response (DDR) in the
      reprogramming of these cells. MAJOR CONCLUSIONS: ESCs have distinct mechanisms to
      protect themselves against DSBs and oxidative stress compared to somatic cells.
      The response to damage and stress is crucial for the maintenance of self-renewal
      and differentiation capacity in SCs. iPSCs appear to reprogram some of the
      responses to genotoxic stress. However, it remains to be determined if iPSCs also
      retain some DDR characteristics of the somatic cells of origin. GENERAL
      SIGNIFICANCE: The mechanisms regulating the genomic integrity in ESCs and iPSCs
      are critical for its safe use in regenerative medicine and may shed light on the
      pathways and factors that maintain genomic stability, preventing diseases such as
      cancer. This article is part of a Special Issue entitled Biochemistry of Stem
      Cells.

PMID- 22995213
TI  - Glutathione synthesis.
AB  - BACKGROUND: Glutathione (GSH) is present in all mammalian tissues as the most
      abundant non-protein thiol that defends against oxidative stress. GSH is also a
      key determinant of redox signaling, vital in detoxification of xenobiotics, and
      regulates cell proliferation, apoptosis, immune function, and fibrogenesis.
      Biosynthesis of GSH occurs in the cytosol in a tightly regulated manner. Key
      determinants of GSH synthesis are the availability of the sulfur amino acid
      precursor, cysteine, and the activity of the rate-limiting enzyme, glutamate
      cysteine ligase (GCL), which is composed of a catalytic (GCLC) and a modifier
      (GCLM) subunit. The second enzyme of GSH synthesis is GSH synthetase (GS). SCOPE
      OF REVIEW: This review summarizes key functions of GSH and focuses on factors
      that regulate the biosynthesis of GSH, including pathological conditions where
      GSH synthesis is dysregulated. MAJOR CONCLUSIONS: GCL subunits and GS are
      regulated at multiple levels and often in a coordinated manner. Key transcription
      factors that regulate the expression of these genes include NF-E2 related factor
      2 (Nrf2) via the antioxidant response element (ARE), AP-1, and nuclear factor
      kappa B (NFkappaB). There is increasing evidence that dysregulation of GSH
      synthesis contributes to the pathogenesis of many pathological conditions. These
      include diabetes mellitus, pulmonary and liver fibrosis, alcoholic liver disease,
      cholestatic liver injury, endotoxemia and drug-resistant tumor cells. GENERAL
      SIGNIFICANCE: GSH is a key antioxidant that also modulates diverse cellular
      processes. A better understanding of how its synthesis is regulated and
      dysregulated in disease states may lead to improvement in the treatment of these
      disorders. This article is part of a Special Issue entitled Cellular functions of
      glutathione.

PMID- 22995217
TI  - Understanding the molecular pathways associated with seed vigor.
AB  - Farmers and growers are constantly looking for high quality seeds able to ensure
      uniform field establishment and increased production. Seed priming is used to
      induce pre-germinative metabolism and then enhance germination efficiency and
      crop yields. It has been hypothesized that priming treatments might also improve
      stress tolerance in germinating seeds, leaving a sort of 'stress memory'.
      However, the molecular bases of priming still need to be clarified and the
      identification of molecular indicators of seed vigor is nowadays a relevant goal
      for the basic and applied research in seed biology. It is generally acknowledged
      that enhanced seed vigor and successful priming depend on DNA repair mechanisms,
      activated during imbibition. The complexity of the networks of DNA damage
      control/repair functions has been only partially elucidated in plants and the
      specific literature that address seeds remains scanty. The DNA repair pathways
      hereby described (Nucleotide and Base Excision Repair, Non-Homologous End
      Joining, Homologous Recombination) play specific roles, all of them being
      critical to ensure genome stability. This review also focuses on some novel
      regulatory mechanisms of DNA repair (chromatin remodeling and small RNAs) while
      the possible use of telomere sequences as markers of aging in seed banks is
      discussed. The significant contribution provided by Electron Paramagnetic
      Resonance in elucidating the kinetics of seed aging, in terms of free radical
      profiles and membrane integrity is reported.

PMID- 22995216
TI  - Molecular symmetry determines the mechanism of a very efficient ultrafast
      excitation-to-heat conversion in Ni-substituted chlorophylls.
AB  - In the Ni-substituted chlorophylls, an ultrafast (<60 fs) deactivation channel is
      created, which is not present in Ni-porphyrins. This observation prompted us to
      investigate in detail the mechanism of excitation-to-heat conversion in Ni
      substituted chlorophylls, experimentally, using time-resolved laser-induced
      optoacoustic spectroscopy, and theoretically, using group theory approach. The Ni
      substituted chlorophylls show exceptional photostability and the optoacoustic
      measurements confirm the prompt and very efficient (100%) excitation-into-heat
      conversion in these complexes. Considering their excellent spectral properties
      and the loss-free excitation-into-heat conversion they are likely to become a new
      class of versatile photocalorimetric references. The curious features of the Ni
      substituted chlorophylls originate from the symmetry of a ligand field created in
      the central cavity. The central N-Ni(2+) bonds, formed via the donation of two
      electrons from each of the sp(2) orbitals of two central nitrogens to an empty
      [Formula: see text] hybrid centered on Ni(2+), have a considerable covalent
      character. The extreme rate of excited state relaxation is then not due to a
      ladder of the metal centered d-states, often invoked in metalloporphyrins, but
      seems to result from a peculiar topology of the potential energy surface (a
      saddle-shaped crossing) due to the covalent character of the N-Ni(2+) bonds. This
      is confirmed by a strong 0->0 character of electronic transitions in these
      complexes indicating a similarity of their equilibrium geometries in the ground
      (S(0)) and the excited states (both Q(X) and Q(Y)). The excitation energy is very
      efficiently converted into molecular vibrations and dissipated as heat, involving
      the central Ni(2+). These Ni-substituted pigments pose a fine exemplification of
      symmetry control over properties of excited states of transition metal complexes.

PMID- 22995215
TI  - Catalytic mechanisms of complex II enzymes: a structural perspective.
AB  - Over a decade has passed since the elucidation of the first X-ray crystal
      structure of any complex II homolog. In the intervening time, the structures of
      five additional integral-membrane complex II enzymes and three homologs of the
      soluble domain have been determined. These structures have provided a framework
      for the analysis of enzymological studies of complex II superfamily enzymes, and
      have contributed to detailed proposals for reaction mechanisms at each of the two
      enzyme active sites, which catalyze dicarboxylate and quinone oxidoreduction,
      respectively. This review focuses on how structural data have augmented our
      understanding of catalysis by the superfamily. This article is part of a Special
      Issue entitled: Respiratory complex II: Role in cellular physiology and disease.

PMID- 22995218
TI  - Proteome analysis of the large and the small rubber particles of Hevea
      brasiliensis using 2D-DIGE.
AB  - The rubber particle is a specialized organelle in which natural rubber is
      synthesised and stored in the laticifers of Hevea brasiliensis (para rubber
      tree). It has been demonstrated that the small rubber particles (SRPs) has higher
      rubber biosynthesis ratio than the large rubber particles (LRPs), but the
      underlying molecular mechanism still remains unknown. In this study, LRPs and
      SRPs were firstly separated from the fresh latex using differential
      centrifugation, and two-dimensional difference in-gel electrophoresis (2D-DIGE)
      combined with MALDI-TOF/TOF was then applied to investigate the proteomic
      alterations associated with the changed rubber biosynthesis capacity between LRPs
      and SRPs. A total of 53 spots corresponding to 22 gene products, were
      significantly altered with the |ratio|>=2.0 and T value <=0.05, among which 15
      proteins were up-regulated and 7 were down-regulated in the SRPs compared with
      the LRPs. The 15 up-regulated proteins in the SRPs included small rubber particle
      protein (SRPP), 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS), phospholipase D
      alpha (PLD alpha), ethylene response factor 2, eukaryotic translation initiation
      factor 5A isoform IV (eIF 5A-4), 70-kDa heat shock cognate protein (HSC 70),
      several unknown proteins, etc., whereas the 7 up-regulated proteins in the LRPs
      were rubber elongation factor (REF, 19.6kDa), ASR-like protein 1, REF-like stress
      related protein 1, a putative phosphoglyceride transfer family protein, beta-1,3
      glucanase, a putative retroelement, and a hypothetical protein. Since several
      proteins related to rubber biosynthesis were differentially expressed between
      LRPs and SRPs, the comparative proteome data may provide useful insights into
      understanding the mechanism involved in rubber biosynthesis and latex coagulation
      in H. brasiliensis.

PMID- 22995219
TI  - Bacterial communities on food court tables and cleaning equipment in a shopping
      mall.
AB  - The food court at a shopping mall is a potential transfer point for pathogenic
      microbes, but to date, this environment has not been the subject of detailed
      molecular microbiological study. We used a combination of culture-based and
      culture-independent approaches to investigate the types and numbers of bacteria
      present on food court tables, and on a food court cleaning cloth. Bacteria were
      found at 102-105 c.f.u./m2 on food court tables and 1010 c.f.u./m2 on the
      cleaning cloth. Tag-pyrosequencing of amplified 16S rRNA genes revealed that the
      dominant bacterial types on the cleaning cloth were genera known to include
      pathogenic species (Stenotrophomonas, Aeromonas), and that these genera were also
      evident at lower levels on table surfaces, suggesting possible cross
      contamination. The evidence suggests a public health threat is posed by bacteria
      in the food court, and that this may be due to cross-contamination between
      cleaning equipment and table surfaces.

PMID- 22995220
TI  - Two-tensor model-based bootstrapping on classified tensor morphologies:
      estimation of uncertainty in fiber orientation and probabilistic tractography.
AB  - In this manuscript, fast and clinically feasible model-based bootstrapping
      algorithms using a geometrically constrained two-tensor diffusion model are
      employed for estimating uncertainty in fiber orientation. A Monte-Carlo-based
      tensor morphology voxel classification algorithm is initially applied using
      single-tensor bootstrap samples before the use of a two-tensor model-based
      bootstrapping algorithm. Classification of tensor morphologies allows the tensor
      morphology to be considered when selecting the most appropriate bootstrap
      procedure. A constrained two-tensor model approach can greatly reduce data
      acquisition and computational times for whole bootstrap data volume generation
      compared to other multifiber model techniques, facilitating widespread clinical
      use. For comparison, we propose a new repetition-bootstrap algorithm based on
      classified voxels and the constrained two-tensor model. Tractography with these
      bootstrapping algorithms is also developed to estimate the connection
      probabilities between brain regions, especially regions with complex fiber
      configurations. Experimental results on synthetic data, a hardware phantom and
      human brain data demonstrate the superior performance of our algorithms compared
      to conventional approaches.

PMID- 22995221
TI  - Initial experience with the Codman Certas adjustable valve in the management of
      patients with hydrocephalus.
AB  - BACKGROUND: A new adjustable valve, the Codman CertasTM valve for treatment of
      hydrocephalus was introduced into clinical practice in January 2011. It has 8
      different settings with an opening pressure varying from 36 to over 400 mm H2O at
      a flow rate of 20 mL/h. The 8th setting is designed to provide a "virtual off"
      function. The objective of this report is to describe the initial clinical
      experience with the CertasTM valve and evaluate clinical usage with the main
      focus on the portable adjustment device - Therapeutic Management System (TMS),
      the "virtual off" setting and compatibility with magnetic resonance imaging
      (MRI). FINDINGS: Forty-two patients with hydrocephalus from different etiologies
      were treated with the CertasTM adjustable shunt system. Data regarding
      implantation procedures, the use of the TMS system, x-ray imaging, and MRI
      procedures were recorded prospectively. All patients had clinical follow-up at
      four weeks after implantation and every three months until a stable clinical
      condition was obtained.The mean time for follow-up was 8.6 months (1-16.6).
      Seventy-one adjustments were performed with the TMS, 12 were problematic. Twenty
      nine MRI procedures were performed and did not cause accidental resetting. Five
      patients were treated with the "virtual off" function for a period. CONCLUSIONS:
      We found the CertasTM valve valuable in the treatment of hydrocephalus, usability
      of the TMS was high because it is small and portable, but in some cases we
      experienced adjustment problems with the first procedures performed by a surgeon,
      indicating that there is a learning curve. The "virtual off" function provided a
      possibility of treating over-drainage without the need for shunt ligation or
      other invasive procedures.

PMID- 22995222
TI  - Association of a single nucleotide polymorphism of the NPR3 gene promoter with
      early onset ischemic stroke in an Italian cohort.
AB  - BACKGROUND: NPR3, located on human chromosome 5 (5p14-p13), encodes the
      natriuretic peptide receptor type C (NPR-C) that is mainly known as the
      natriuretic peptide clearance receptor. Involvement of NPR3 in susceptibility to
      cardiovascular diseases, i.e. hypertension, has been previously shown. With
      regard to stroke predisposition, evidence for a potential role of genetic
      variation within or nearby NPR3 has been suggested by a previous genome wide
      association study. METHODS: We investigated the contribution to early-onset
      ischemic stroke susceptibility of the NPR3 -55 C>A transition by genotyping this
      variant in an Italian cohort of 368 cases and 335 controls. RESULTS: In a
      multivariable logistic regression analysis adjusting for age, gender,
      hypertension, hypercholesterolemia, smoking habit and diabetes, a significant
      association of the -55 AA genotype with stroke was observed (OR=3.2, 95% CI 1.2
      8.3, p=0.016). Remarkably, the polymorphism remained associated with stroke after
      adjusting for hypertensive status. CONCLUSION: Our observation obtained in an
      Italian cohort of early onset ischemic strokes suggests that a NPR3 promoter gene
      variant could have a role on cerebrovascular disease susceptibility.

PMID- 22995223
TI  - JAK2 the future: therapeutic strategies for JAK-dependent malignancies.
AB  - The Janus kinase (JAK) proteins are a family of intracellular nonreceptor
      tyrosine kinases involved in cytokine signaling via the JAK-STAT (signal
      transducers and activators of transcription) pathway. Genetic studies have
      identified somatic JAK2(V617F) mutations and other mutant alleles that activate
      JAK-STAT signaling in most patients with myeloproliferative neoplasms (MPNs). As
      a result, JAK inhibitors have been developed to treat various malignancies and
      have been shown to be efficacious in both preclinical and clinical settings.
      However, available ATP-competitive JAK (type I) inhibitors are associated with
      dose-dependent toxicities, and do not yet reduce disease burden in MPN patients.
      Recent studies suggest that genetic and epigenetic mechanisms can cause
      insensitivity to type I JAK inhibitors. Novel therapies include the development
      of type II JAK inhibitors and the use of alternative strategies to abrogate JAK
      STAT signaling, perhaps with histone deacetylase (HDAC) and heat shock protein 90
      (HSP90) inhibitors. These innovative therapies may translate to treatment of
      other diseases that are dependent on JAK signaling, including B-precursor acute
      lymphoblastic leukemia (B-ALL).

PMID- 22995224
TI  - Hospital discharge diagnostic and procedure codes for upper gastro-intestinal
      cancer: how accurate are they?
AB  - BACKGROUND: Population-level health administrative datasets such as hospital
      discharge data are used increasingly to evaluate health services and outcomes of
      care. However information about the accuracy of Australian discharge data in
      identifying cancer, associated procedures and comorbidity is limited. The
      Admitted Patients Data Collection (APDC) is a census of inpatient hospital
      discharges in the state of New South Wales (NSW). Our aim was to assess the
      accuracy of the APDC in identifying upper gastro-intestinal (upper GI) cancer
      cases, procedures for associated curative resection and comorbidities at the time
      of admission compared to data abstracted from medical records (the 'gold
      standard'). METHODS: We reviewed the medical records of 240 patients with an
      incident upper GI cancer diagnosis derived from a clinical database in one NSW
      area health service from July 2006 to June 2007. Extracted case record data was
      matched to APDC discharge data to determine sensitivity, positive predictive
      value (PPV) and agreement between the two data sources (kappa-coefficient).
      RESULTS: The accuracy of the APDC diagnostic codes in identifying site-specific
      incident cancer ranged from 80-95% sensitivity. This was comparable to the
      accuracy of APDC procedure codes in identifying curative resection for upper GI
      cancer. PPV ranged from 42-80% for cancer diagnosis and 56-93% for curative
      surgery. Agreement between the data sources was >0.72 for most cancer diagnoses
      and curative resections. However, APDC discharge data was less accurate in
      reporting common comorbidities - for each condition, sensitivity ranged from 9
      70%, whilst agreement ranged from kappa = 0.64 for diabetes down to kappa < 0.01
      for gastro-oesophageal reflux disorder. CONCLUSIONS: Identifying incident cases
      of upper GI cancer and curative resection from hospital administrative data is
      satisfactory but under-ascertained. Linkage of multiple population-health
      datasets is advisable to maximise case ascertainment and minimise false
      positives. Consideration must be given when utilising hospital discharge data
      alone for generating comorbidity indices, as disease burden at the time of
      admission is under-reported.

PMID- 22995225
TI  - Magnetic resonance imaging of paratesticular inflammatory pseudotumor: a case
      report.

PMID- 22995226
TI  - Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of
      dietary fat content, tissue type and sex in adipose and muscle tissues.
AB  - BACKGROUND: DOR/TP53INP2 acts both at the chromosomal level as a nuclear co
      factor e.g. for the thyroid hormone receptor and at the extrachromosomal level as
      an organizing factor of the autophagosome. In a previous study, DOR was shown to
      be down-regulated in skeletal muscle of obese diabetic Zucker fa/fa rats.
      METHODS: To identify sites of differential DOR expression in metabolically active
      tissues, we measured differences in DOR expression in white adipose tissue (WAT),
      brown adipose tissue (BAT), skeletal muscle (SM) and heart muscle (HM) by qPCR.
      To assess whether DOR expression is influenced in the short term by nutritional
      factors, NMRI mice were fed different fat rich diets (fat diet, FD: 18% or high
      fat diet, HFD: 80% fat) for one week and DOR expression was compared to NMRI mice
      fed a control diet (normal diet, ND: 3.3% fat). Additionally, DOR expression was
      measured in young (45 days old) and adult (100 days old) genetically obese
      (DU6/DU6i) mice and compared to control (DUKs/DUKsi) animals. RESULTS: ANOVA
      results demonstrate a significant influence of diet, tissue type and sex on DOR
      expression in adipose and muscle tissues of FD and HFD mice. In SM, DOR
      expression was higher in HFD than in FD male mice. In WAT, DOR expression was
      increased compared to BAT in male FD and HFD mice. In contrast, expression levels
      in female mice were higher in BAT for both dietary conditions.DOR expression
      levels in all tissues of 100 days old genetically obese animals were mainly
      influenced by sex. In HM, DOR expression was higher in male than female animals.
      CONCLUSIONS: DOR expression varies under the influence of dietary fat content,
      tissue type and sex. We identified target tissues for further studies to analyze
      the specific function of DOR in obesity. DOR might be part of a defense mechanism
      against fat storage in high fat diets or obesity.

PMID- 22995227
TI  - New paradigm for patient-reported outcomes assessment in foot & ankle research:
      computerized adaptive testing.
AB  - BACKGROUND: Accurately measuring, reporting and comparing outcomes is essential
      for improving health care delivery. Current challenges with available health
      status scales include patient fatigue, floor/ceiling effects and
      validity/reliability. METHODS: This study compared Patient Reported Outcomes
      Measurement Information System (PROMIS)-based Lower Extremity Physical Function
      Computerized Adaptive Test (LE CAT) and two legacy scales -the Foot and Function
      Index (FFI) and the sport module from the Foot and Ankle Ability Measure (spFAAM)
      -for 287 patients scheduled for elective foot and ankle surgery. We documented
      the time required by patients to complete the instrument, instrument precision,
      and the extent to which each instrument covered the full range of physical
      functioning across the patient sample. RESULTS: Average time of test
      administration: 66 seconds for LE CAT, 130 seconds for spFAAM and 239 seconds for
      FFI. All three instruments were fairly precise at intermediate physical
      functioning levels (i.e., Standard Error of Measurement < 0.35), were relatively
      less precise at the higher trait levels and the LE CAT maintained precision in
      the lower range while the spFAAM and FFI's had decreased precision. The LE CAT
      had less floor/ceiling effects than the FFI and the spFAAM. CONCLUSION: The LE
      CAT showed considerable advantage compared to legacy scales for measuring patient
      reported outcomes in orthopaedic patients with foot and ankle problems. CLINICAL
      RELEVANCE: A paradigm shift to broader use of PROMIS-based CATs should be
      considered to improve precision and reduce patient burden with patient-reported
      outcome measuremen foot and ankle patients.

PMID- 22995228
TI  - Correlation of intra-articular ankle pathology with cytokine biomarkers and
      matrix degradation products.
AB  - BACKGROUND: Articular cartilage degeneration is mediated by inflammatory
      cytokines and fragments of structural matrix proteins. Few studies have examined
      the role of these biomarkers in intra-articular pathology of the ankle. METHODS:
      Four groups of patients with increasing ankle pathology were enrolled. Group 1
      included controls with no pain who underwent unrelated forefoot surgery. Group 2
      included patients undergoing arthroscopy with intraoperative mild chondrosis.
      Group 3 included patients undergoing arthroscopy with moderate/severe chondrosis,
      osteochondral lesions, impingement, or loose bodies. Group 4 included positive
      controls with severe arthrosis undergoing ankle arthrodesis/arthroplasty. Ankle
      fluid was obtained by intra-articular aspiration and was assayed for IL-6, IFN
      gamma, MCP, MIP-1beta, and fibronectin-aggrecan complex (FAC), a matrix
      degradation marker. There were 36 patients total, 21 males and 15 females with a
      mean age 45 (+/-16; range 18 to 76) years and a mean VAS for pain of 4.7 (+/-3.5;
      range 0 to 9). In groups 1 through 4, there were 11, 6, 15 and 4 patients
      respectively. RESULTS: The mean values of MCP-1 were 49.8 (+/-8.0) for minimal
      pathology and 133.9 (+/-33.0) for substantial pathology (pg/ml). The mean values
      of the FAC were 2.83 (+/-1.16) for minimal pathology and 9.62 (+/-2.23) for
      substantial pathology (optical density at 450 nm). The groups differed
      significantly in age, preoperative VAS, FAC, IL-6, and MCP-1 (p<0.05).
      CONCLUSION: There are differences in FAC and MCP-1 with increasing grades of
      severity of intra-articular pathology. CLINICAL RELEVANCE: These tests may play a
      role in determining the necessity for arthroscopy or intra-articular procedures
      in equivocal candidates.

PMID- 22995229
TI  - Evidence-based indications for distraction ankle arthroplasty.
AB  - BACKGROUND: The purpose of this study was to review the literature to provide a
      comprehensive description of the Level of Evidence (LOE) available to support the
      operative technique of distraction ankle arthroplasty for the current generally
      accepted indications and make a grade of recommendation for each. METHODS: A
      comprehensive review of the literature was performed (November 2010 to January
      2011) using the PubMed database. The abstracts from these searches were reviewed
      to isolate literature that described therapeutic studies investigating the
      results of distraction ankle arthroplasty. All articles were reviewed and
      assigned a classification (I-V) of Level of Evidence. An analysis of the
      literature reviewed was used to assign a Grade of Recommendation for each current
      generally accepted indication for distraction ankle arthroplasty. RESULTS: There
      is insufficient evidence based literature (Grade I) to support or refute the
      procedure for either: post-traumatic ankle arthritis, arthritis associated with
      ligamentous instability, primary degenerative joint disease, chondrolysis,
      deformity associated with arthritis, osteochondral defects and congenital ankle
      abnormalities. CONCLUSION: Inadequate evidence based literature exists to support
      or refute all currently accepted indications for distraction ankle arthroplasty
      and further high quality, scientific studies are needed upgrade to these
      recommendations.

PMID- 22995230
TI  - Outcomes of proximal chevron osteotomy for moderate versus severe hallux valgus
      deformities.
AB  - BACKGROUND: Proximal chevron osteotomy with a distal soft tissue procedure has
      been widely used to treat moderate to severe hallux valgus deformities. However,
      there have been no studies comparing the results of proximal chevron osteotomy
      between patients with moderate and severe hallux valgus. We compared the results
      of this procedure among these groups. METHODS: A retrospective review of 95
      patients (108 feet) that underwent proximal chevron osteotomy and distal soft
      tissue procedure for moderate and severe hallux valgus was conducted. The 108
      feet were divided into two groups: moderate hallux valgus (Group A) and severe
      hallux valgus (Group B). Group A was composed of 57 feet (52 patients) and Group
      B of 51 feet (43 patients). Average followup was 45 months. RESULTS: Mean
      American Orthopedic Foot and Ankle Society hallux metatarsophalangeal
      interphalangeal scores were 54.1 points in Group A and 53.0 points in Group B
      preoperatively, and these improved to 90.8 and 92.6, respectively, at the last
      followup. Mean hallux valgus angles in Groups A and B reduced from 32.3 and 40.8
      degrees, preoperatively to 10.7 and 13.2 degrees, postoperatively. Similarly,
      mean first intermetatarsal angles in Groups A and B reduced from 15.0 and 19.2
      degrees, preoperatively to 9.0 and 9.2 degrees, postoperatively. CONCLUSION: The
      clinical and radiographic outcomes of proximal chevron osteotomy with a distal
      soft tissue procedure were found to be comparable for moderate and severe hallux
      valgus. Accordingly, our results suggest that this procedure provides an
      effective and reliable means of correcting hallux valgus regardless of severity
      of deformity.

PMID- 22995231
TI  - The development of a neuropathic ankle following successful correction of non
      plantigrade charcot foot deformity.
AB  - BACKGROUND: The treatment of Charcot foot arthropathy has traditionally involved
      immobilization during the acute phase followed by longitudinal management with
      accommodative bracing. In response to the perceived poor outcomes associated with
      nonoperative accommodative treatment, many experts now advise surgical correction
      of the deformity, especially when the affected foot is not clinically
      plantigrade. The significant rate of surgical and medical-associated morbidity
      accompanying this form of treatment has led surgeons to look for improved methods
      of surgical stabilization, including the use of the circular ring external
      fixation. METHODS: Over a 7-year period, a single surgeon performed surgical
      correction of non-plantigrade Charcot foot deformity on 171 feet in 164 patients
      with a statically applied circular external fixator. Following successful
      correction, five patients developed a neuropathic deformity of the ipsilateral
      ankle after removal of the external fixator and subsequent weight bearing total
      contact cast. RESULTS: Three of the five patients progressed to successful
      healing of the neuropathic (Charcot) ankle arthropathy following treatment with a
      series of weightbearing total contact casts. Two underwent successful ankle
      fusion with retrograde locked intramedullary nailing. DISCUSSION: This unusual
      clinical scenario likely represents either a progression of the disease process
      in the foot or a complication associated with surgical correction of the original
      neuropathic foot deformity. A better understanding of this observation will
      likely become apparent as we acquire more experience with this disorder.

PMID- 22995232
TI  - Use of a geometric formula to improve the radiographic correction achieved by the
      scarf osteotomy.
AB  - BACKGROUND: Many procedures for hallux valgus treatment have high recurrence
      rates, often related to operative considerations such as accuracy of deformity
      correction, soft tissue balancing and sesamoid alignment. Inadequate distal
      metatarsal-articular angle (DMAA) correction is common with uni- and bi-planar
      osteotomies which principally address the inter-metatarsal angle (IMA). The scarf
      osteotomy is a tri-planar osteotomy which corrects the DMAA and IMA, thereby
      achieving a more anatomical correction and potentially reducing the recurrence
      rate. Our hypothesis was that by controlling the length and relative proximal and
      distal translations of the scarf with a geometric formula, more accurate
      correction of the IMA and DMAA is possible. METHODS: A formula was generated to
      determine the specific adjustments required to correct the deformity. A
      prospective trial was performed to assess the accuracy of this formula. Thirty
      four adult patients were enrolled in the study. Seventeen patients underwent a
      standard scarf procedure; 17 were operated on using the corrections prescribed by
      the formula. RESULTS: Hallux valgus angle (HVA), IMA and DMAA corrections
      improved with the formula (p = 0.036, p = 0.049, and p = 0.006, respectively).
      Patient and procedure selection has changed in our unit as a result of this
      study, which identified some preoperative deformities as beyond the capabilities
      of the scarf procedure. CONCLUSION: The formula allows precise, reproducible,
      anatomical correction of IMA and DMAA deformities. The degree of correction
      attainable with the scarf is dependent on the first metatarsal width and the
      preoperative deformities. The formula highlighted the limitations of the scarf,
      thereby aiding in appropriate patient and procedure selection.

PMID- 22995233
TI  - Medial distal tibial angle: comparison between weightbearing mortise view and
      hindfoot alignment view.
AB  - BACKGROUND: The medial distal tibial angle (MDTA) is used to determine ankle
      alignment. The mortise view is the standard to measure MDTA, but the hindfoot
      alignment view (HAV) has become popular. The MDTA may vary between views,
      influencing the choice of surgery. METHODS: The MDTA was compared between the
      mortise and HAV in 146 ankles. MDTA was correlated to age and sagittal tibial
      tilt for each view. Differences in MDTA by gender and ethnicity were assessed.
      Diagnostic agreement (varus, valgus, normal) between views was calculated.
      Clinical assessment of alignment was determined and percent agreement between
      clinical and radiographic alignment was quantified. RESULTS: The MDTA measured
      from the mortise view and HAV radiographs was 89.0 (range, 81 to 96 degrees; SD =
      2.8) degrees and 86.0 (range, 73 to 95 degrees; SD = 3.5) degrees, respectively.
      The MDTA was comparable for both genders for mortise (p = 0.356) and HAV (p =
      0.621). The MDTA was comparable in all ethnic groups for mortise view (p = 0.616)
      and HAV (p = 0.916). Correlation between the measured MDTA and age was not
      statistically significant for both the mortise (r = 0.118; p = 0.158) and HAV (r
      = 0.148; p = 0.074). In only 47.3% of all ankles was the radiographic diagnosis
      of alignment the same between views. Agreement between clinical and radiographic
      classifications was 60.3% for the mortise view and 52.8% for the HAV. CONCLUSION:
      Substantial disagreement in primary alignment was found between the mortise and
      HAV as quantified by the MDTA. Agreement between clinical and radiographic
      alignment was also poor. CLINICAL RELEVANCE: Advanced imaging such as CT or MRI
      may better describe ankle alignment.

PMID- 22995234
TI  - Arthroscopic treatment of osteochondral lesions of the tibial plafond.
AB  - BACKGROUND: Osteochondral lesions of the distal tibial plafond (OLTPs) are an
      uncommon problem. The purpose of this study was to evaluate clinical outcomes
      following arthroscopic treatment of OLTPs. METHODS: Retrospective chart review
      was performed on all patients treated arthroscopically for OLTPs. Treatment
      consisted of generalized synovectomy followed by curettage of the lesion and
      microfracture. If a cartilage cap was intact, antegrade drilling was performed.
      Cystic defects were treated with curettage of the cyst and filling of any defect
      with bone graft. RESULTS: A total of 13 patients were included. Nine patients had
      isolated lesions, while four had lesions of the distal tibial plafond and talar
      dome. Average followup was 156 (range, 38 to 402 +/- 117.9) weeks and average
      patient age was 32.9 (range, 14 to 50 +/- 11.8) years. Eleven of 13 patients were
      available for followup modified AOFAS score. The average preoperative score was
      35.2 (range, 24 to 49 +/- 7.1). The average postoperative modified AOFAS score
      was 50.4 (range, 33 to 56 +/- 7.6). There were four patients (30.8%) with a poor
      outcome. CONCLUSION: OLTPs can be challenging to treat. Arthroscopic treatment
      can lead to improved outcomes. However, the higher incidence of poor outcomes in
      our series may indicate less predictability in the treatment of OLTPs and that
      outcomes may not be equivalent to previous reported studies on OLTPs or
      osteochondral lesions of the talus.

PMID- 22995235
TI  - Mechanical stability of a locked step-plate versus single compression screw
      fixation for medial displacement calcaneal osteotomy.
AB  - BACKGROUND: Reconstruction of a flatfoot commonly involves a calcaneal Medial
      Displacement Osteotomy (MDO) to correct hindfoot valgus in combination with soft
      tissue procedures. We compared fixation of an MDO using either a single, large
      cannulated screw versus a locking step-plate in load to failure in a cadaveric
      model. METHODS: Eight matched pairs of cadaveric limbs were loaded using a
      mechanical testing rig. Two pairs served as non-operated controls. The remaining
      paired limbs underwent a 10-mm MDO stabilized either with a single 7-mm screw or
      a step-plate with four locking screws. One pair was used as a pilot study and the
      remaining five pairs were loaded up to 4500 N to failure. RESULTS: In the five
      pairs loaded to failure, the median (with 95% CI) maximum force were 1779 N (1099
      2312) and 826 N (288-1607) for the plate and screw, respectively (p = 0.043).
      With single screw fixation, the tuberosity fragment consistently failed by
      rotation and angulation into varus. With plate fixation, failure occurred as the
      screws cut through the internal surfaces of the tuberosity and body with no
      failure at the screw-plate interface. CONCLUSION: In this cadaveric model, a
      locked step-plate supported a significantly higher maximum force than a single
      large cannulated screw. CLINICAL RELEVANCE: The magnitude of the load supported
      by the locking step-plate suggests that allowing early weightbearing post
      operation may be safe in clinical practice before union of the osteotomy.

PMID- 22995236
TI  - Simian foot at skeletal maturity: long-term case report followup.

PMID- 22995237
TI  - Conversion of painful ankle arthrodesis to bipolar fresh osteochondral allograft:
      case report.

PMID- 22995238
TI  - Subtalar instability reconstruction with an allograft: technical note.

PMID- 22995239
TI  - Dunking the knot in suture button fixation for distal tibiofibular syndesmosis
      injury: technique tip.

PMID- 22995240
TI  - Life without the AOFAS score: a critical problem in a time of scarcity.

PMID- 22995242
TI  - Electrochemical oxidation of reverse osmosis concentrate on boron-doped diamond
      anodes at circumneutral and acidic pH.
AB  - Electrochemical processes have been widely investigated for degrading organic
      contaminants present in wastewater. This study evaluated the performance of
      electrochemical oxidation using boron-doped diamond (BDD) electrodes by forming
      OH() for the treatment of reverse osmosis concentrate (ROC) from secondary
      treated wastewater effluents. Since oxidation by OH() and active chlorine species
      (HClO/ClO(-)) is influenced by pH, the electrochemical oxidation of ROC was
      evaluated at controlled pH 6-7 and at pH 1-2 (no pH adjustment). A high
      concentration of chloride ions in the ROC enhanced the oxidation, and 7-11% of
      Coulombic efficiency for chemical oxygen demand (COD) removal was achieved with
      5.2 Ah L(-1) of specific electrical charge. Complete COD removal was observed
      after 5.2 and 6.6 Ah L(-1), yet the corresponding dissolved organic carbon (DOC)
      removal was only 48% (at acidic pH) and 59% (at circumneutral pH). Although a
      higher operating pH seemed to enhance the participation of OH() in oxidation
      mechanisms, high concentrations of chloride resulted in the formation of
      significant concentrations of adsorbable organic chlorine (AOCl) after
      electrochemical oxidation at both pH. While adsorbable organic bromine (AOBr) was
      degraded at a higher applied electrical charge, a continuous increase in AOCl
      concentration (up to 0.88 mM) was observed until the end of the experiments (i.e.
      10.9 Ah L(-1)). In addition, total trihalomethanes (tTHMs) and total haloacetic
      acids (tHAAs) were further degraded with an increase in electrical charge under
      both pH conditions, to final total concentrations of 1 and 4 MUM (tTHMs), and 12
      and 22 MUM (tHAAs), at acidic and circumneutral pH, respectively. In particular,
      tHAAs were still an order of magnitude above their initial concentration in ROC
      after further electrooxidation. Where high chloride concentrations are present,
      it was found to be necessary to separate chloride from ROC prior to
      electrochemical oxidation in order to avoid the formation of chlorinated by
      products.

PMID- 22995243
TI  - Enzyme-catalyzed hydrolysis of the supported phospholipid bilayers studied by
      atomic force microscopy.
AB  - Atomic force microscopy (AFM) is employed to reveal the morphological changes of
      the supported phospholipid bilayers hydrolyzed by a phospholipase A(2) (PLA(2))
      enzyme in a buffer solution at room temperature. Based on the high catalytic
      selectivity of PLA(2) toward l-enantiomer phospholipids, five kinds of supported
      bilayers made of l- and D-dipalmitoylphosphatidylcholines (DPPC), including l
      DPPC (upper leaflet adjacent to solution)/l-DPPC (bottom leaflet) (or l/l in
      short), l/d, d/l, d/d, and racemic ld/ld, were prepared on a mica surface in gel
      phase, to explicate the kinetics and mechanism of the enzyme-induced hydrolysis
      reaction in detail. AFM observations for the l/l bilayer show that the hydrolysis
      rate for l-DPPC is significantly increased by PLA(2) and most of the hydrolysis
      products desorb from substrate surface in 40 min. As d-enantiomers are included
      in the bilayer, the hydrolysis rate is largely decreased in comparison with the
      l/l bilayer. The time used to hydrolyze the as-prepared bilayers by PLA(2)
      increases in the sequence of l/l, l/d, ld/ld, and d/l (d/d is inert to the enzyme
      action). d-enantiomers in the enantiomer hybrid bilayers remain on the mica
      surface at the end of the hydrolysis reaction. It was confirmed that the
      hydrolysis reaction catalyzed by PLA(2) preferentially occurs at the edges of
      pits or defects on the bilayer surface. The bilayer structures are preserved
      during the hydrolysis process. Based on these observations, a novel kinetics
      model is proposed to quantitatively account for the PLA(2)-catalyzed hydrolysis
      of the supported phospholipid bilayers. The model simulation demonstrates that
      PLA(2) mainly binds with lipids at the perimeter of defects in the upper leaflet
      and leads to a hydrolysis reaction, yielding species soluble to the solution
      phase. The lipid molecules underneath subsequently flip up to the upper leaflet
      to maintain the hydrophilicity of the bilayer structure. Our analysis shows that
      d-enantiomers in the hybrid bilayers considerably reduce the hydrolysis rate by
      its ineffective binding with PLA(2).

PMID- 22995244
TI  - The determinants of hydrophobic mismatch response for transmembrane helices.
AB  - Hydrophobic mismatch arises from a difference in the hydrophobic thickness of a
      lipid membrane and a transmembrane protein segment, and is thought to play an
      important role in the folding, stability and function of membrane proteins. We
      have investigated the possible adaptations that lipid bilayers and transmembrane
      alpha-helices undergo in response to mismatch, using fully-atomistic molecular
      dynamics simulations totaling 1.4 MUs. We have created 25 different tryptophan
      alanine-leucine transmembrane alpha-helical peptide systems, each composed of a
      hydrophobic alanine-leucine stretch, flanked by 1-4 tryptophan side chains, as
      well as the beta-helical peptide dimer, gramicidin A. Membrane responses to
      mismatch include changes in local bilayer thickness and lipid order, varying
      systematically with peptide length. Adding more flanking tryptophan side chains
      led to an increase in bilayer thinning for negatively mismatched peptides, though
      it was also associated with a spreading of the bilayer interface. Peptide
      tilting, bending and stretching were systematic, with tilting dominating the
      responses, with values of up to ~45 degrees  for the most positively mismatched
      peptides. Peptide responses were modulated by the number of tryptophan side
      chains due to their anchoring roles and distributions around the helices.
      Potential of mean force calculations for local membrane thickness changes, helix
      tilting, bending and stretching revealed that membrane deformation is the least
      energetically costly of all mismatch responses, except for positively mismatched
      peptides where helix tilting also contributes substantially. This comparison of
      energetic driving forces of mismatch responses allows for deeper insight into
      protein stability and conformational changes in lipid membranes.

PMID- 22995245
TI  - Searching for a conceptual language in Systems Biology: Hints from Statistical
      Mechanics?
AB  - The search for a unified framework describing the causal structure of biological
      entities is one of the main aims of Systems Biology. This comment tries to make
      the point that universal structures may be found in Systems Biology, in analogy
      with the success of Statistical Mechanics in describing a large variety of
      different physical systems in a single conceptual framework.

PMID- 22995246
TI  - Sorption of Pb2+ on mercapto functionalized sepiolite.
AB  - Mercapto functionalized sepiolite (MSEP) was prepared by nanotexturization method
      and applied for the sorption of Pb(2+) from aqueous solution. These samples
      before and after sorption were characterized through XRD, FT-IR, (29)Si and (13)C
      CP/MAS NMR and XPS. The sorption behaviors including thermodynamic and kinetic
      parameters, effect factors and mechanisms of Pb(2+) sorption on MSEP were
      studied. The maximum sorption amounts of 97 mg g(-1). The parameters DeltaH(0)
      and DeltaS(0) were 33.637 kJ mol(-1) and 202.697 J mol(-1) K(-1), respectively.
      Freundlich isotherm was proved to describe the sorption data better than other
      isotherms and pseudo second order kinetic model could fit the sorption kinetic
      processes well. The pH influenced the sorption of Pb(2+) on MSEP significantly
      but background electrolytes have relative weak effect. Based on hard and soft
      acids and bases theory and the results analyzed from XPS, the sorption mechanisms
      could be explained as primarily chemical adsorption and secondary physical
      adsorption.

PMID- 22995247
TI  - A simpler expression for Henry's function describing the electrophoretic mobility
      of spherical colloids.
AB  - An approximate expression for Henry's function, describing the electrophoretic
      mobility of a spherical colloidal particle in the limit of low surface
      potentials, is developed through a physical analogy to a colloidal particle with
      a linearly slipping surface (i.e. satisfies the Navier slip condition). The
      resulting expression reproduces Henry's function with a relative error of no more
      than 0.1%. This approach is generalized for the electrophoretic mobility of a
      particle regardless of surface potential though necessary data for rigorous
      testing is lacking.

PMID- 22995248
TI  - Highly fluorescent colloids based on rhodamine 6G, modified layered silicate, and
      organic solvent.
AB  - Synthetic layered silicate saponite was modified with dodecyltrimethylammonium
      (C12), octadecyltrimethylammonium (C18), and dioctadecyldimethylammonium (2C18)
      cations for use as sorbents of the laser dye, rhodamine 6G (R6G). Via solvent
      exchange, transparent colloids in xylene were prepared and investigated using
      absorption and fluorescence spectroscopies. Molecular aggregation and partial
      quenching of the fluorescence were observed for the colloids based on 2C18
      cations. Maximal fluorescence yields were observed for the colloids with C12 and
      C18 cations. Transparent gels without an apparent loss of luminescent efficiency
      could be prepared by concentrating the colloids. These highly fluorescent
      colloids and gels represent new types of materials with interesting optical
      properties.

PMID- 22995249
TI  - A new method for producing "Lotus Effect" on a biomimetic shark skin.
AB  - Nature has long been an important source of inspiration for mankind to develop
      artificial ways to mimic the remarkable properties of biological systems. In this
      work, a new method was explored to fabricate a superhydrophobic dual-biomimetic
      surface comprising both the shark-skin surface morphology and the lotus leaf-like
      hierarchical micro/nano-structures. The biomimetic surface possessing shark-skin
      pattern microstructure was first fabricated by microreplication of shark-skin
      surface based on PDMS; and then it was treated by flame to form hierarchical
      micro/nano-structures that can produce lotus effect. The fabricated biomimetic
      surfaces were characterized with scanning electron microscopy (SEM), water
      contact angle measurements and liquid drop impact experiments. The results show
      that the fabricated dual-biomimetic surface possesses both the vivid shark-skin
      surface morphology and the lotus leaf-like hierarchical micro/nano-structures. It
      can exhibit excellent superhydrophobicity that the contact angle is as high as
      160 degrees  and maintain its robustness of the superhydrophobicity during the
      droplet impact process at a relatively high Weber number. The mechanism of the
      micromorphology evolution and microstructural changes on the biomimetic shark
      skin surface was also discussed here in the process of flame treatment. This
      method is expected to be developed into a novel and feasible biomimetic surface
      manufacturing technique.

PMID- 22995250
TI  - When does pain matter? Acknowledging the subjectivity of clinical significance.

PMID- 22995252
TI  - Molecular dissection of premalignant colorectal lesions reveals early onset of
      the CpG island methylator phenotype.
AB  - The concept of the CpG island methylator phenotype (CIMP) in colorectal cancer
      (CRC) is widely accepted, although the timing of its occurrence and its
      interaction with other genetic defects are not fully understood. Our aim in this
      study was to unravel the molecular development of CIMP cancers by dissecting
      their genetic and epigenetic signatures in precancerous and malignant colorectal
      lesions. We characterized the methylation profile and BRAF/KRAS mutation status
      in 368 colorectal tissue samples, including precancerous and malignant lesions.
      In addition, genome-wide copy number aberrations, methylation profiles, and
      mutations of BRAF, KRAS, TP53, and PIK3CA pathway genes were examined in 84
      colorectal lesions. Genome-wide methylation analysis of CpG islands and selected
      marker genes revealed that CRC precursor lesions are in three methylation
      subgroups: CIMP-high, CIMP-low, and CIMP-negative. Interestingly, a subset of
      CIMP-positive malignant lesions exhibited frequent copy number gains on
      chromosomes 7 and 19 and genetic defects in the AKT/PIK3CA pathway genes.
      Analysis of mixed lesions containing both precancerous and malignant components
      revealed that most aberrant methylation is acquired at the precursor stage,
      whereas copy number aberrations are acquired during the progression from
      precursor to malignant lesion. Our integrative genomic and epigenetic analysis
      suggests early onset of CIMP during CRC development and indicates a previously
      unknown CRC development pathway in which epigenetic instability associates with
      genomic alterations.

PMID- 22995253
TI  - Clinical presentation and self-reported patterns of pain and function in patients
      with plantar heel pain.
AB  - BACKGROUND: Plantar heel pain is a common disorder of the foot. The purpose of
      this study was to explore the relationship between duration of symptoms in
      plantar fasciitis patients and demographic factors, the intensity and location of
      pain, extent of previous treatment, and self-reported pain and function. METHODS:
      The charts of patients presenting with plantar heel pain between June 2008 and
      October 2010 were reviewed retrospectively and 182 patients with a primary
      diagnosis of plantar fasciitis were identified. Patients with symptoms less than
      6 months were identified as acute and patients with symptoms greater than or
      equal to 6 months were defined as having chronic symptoms. Comparisons based on
      duration of symptoms were performed for age, gender, body mass index (BMI),
      comorbidities, pain location and intensity, and a functional score measured by
      the Foot and Ankle Ability Measure (FAAM). RESULTS: The two groups were similar
      in age, BMI, gender, and comorbidities. Pain severity, as measured by a visual
      analog scale, was not statistically significant between the two groups (6.6 and
      6.2). The acute and chronic groups of patients reported similar levels of
      function on both the activity of daily living (62 and 65) and sports (47 and 45)
      subscales of the FAAM. Patients in the chronic group were more likely to have
      seen more providers and tried more treatment options for this condition.
      CONCLUSION: As plantar fasciitis symptoms extend beyond 6 months, patients do not
      experience increasing pain intensity or functional limitation. No specific risk
      factors have been identified to indicate a risk of developing chronic symptoms.

PMID- 22995254
TI  - Functional outcomes after ankle arthrodesis in elderly patients.
AB  - BACKGROUND: Ankle arthrodesis has been the gold standard operative treatment for
      ankle arthritis refractory to nonoperative treatment. Although multiple studies
      have evaluated the outcomes after ankle fusion, none has focused on outcomes in
      elderly patients. The purpose of this study was to evaluate outcomes of ankle
      fusion in patients over the age of 70. METHODS: Thirty patients (30 ankles) over
      the age of 70 who underwent ankle fusion were identified. Average age at the time
      of surgery was 74.5 years (+/-3.7). The Foot and Ankle Ability Measure (FAAM) was
      obtained postoperatively in 22 of the 23 patients still living. Radiographs were
      followed until union with an average followup of 2.2 years. RESULTS: Union was
      achieved in 27 of 30 ankles (90%). Postoperative radiographs showed 11 (36.6%)
      patients had progression of subtalar arthritis. The average postoperative FAAM
      score was 81.5 (+/-18.3) with an average followup of 8.5 years (+/-1.7).
      Subjectively, when asked to compare present function with their prearthritic
      state, the average response was 75.1% (+/-19.6). The average American Orthopaedic
      Foot and Ankle Society hindfoot score was 73.0 (+/-11.5). Complications included
      nonunion, deep infection, and adjacent joint arthritis. CONCLUSIONS: In this
      clinical cohort, ankle fusion was found to be effective in the treatment of ankle
      arthritis. Functional outcome was satisfactory and the rate of union was
      comparable with that previously reported in the literature for younger patients.
      Although total ankle arthroplasty is becoming increasingly popular, ankle
      arthrodesis is an effective surgical treatment option in an elderly patient
      population.

PMID- 22995255
TI  - Sesamoidectomy for hallux sesamoid fractures.
AB  - BACKGROUND: Hallux sesamoid fractures are challenging to treat. Symptomatic
      nonunion is a common problem after nonoperative treatment. Surgical fixation of
      the fracture can result in successful union, but is technically challenging and
      can be associated with prolonged return to activities (RTA). Sesamoidectomy is an
      alternative surgical option that may provide reliable outcomes and allow an
      earlier RTA in athletes. The purpose of this case-series study was to evaluate a
      cohort of athletic patients with a hallucal sesamoid fracture treated with
      sesamoidectomy. METHODS: A total of 24 patients with 24 sesamoid fractures that
      failed to respond to nonoperative measures were treated surgically with
      sesamoidectomy. Patients' age, level of activity, fractured bone, surgical
      approach, time required to RTA, and postoperative complications were recorded.
      Pre- and postoperative pain was assessed with a visual analog scale ranging from
      zero (no pain) to 10 (intense pain). Five patients were classified as elite
      athletes playing at an intercollegiate level and 19 were classified as active
      individuals performing an athletic activity at least three times per week. The
      mean patient age was 32.2 +/- 10.4 (range, 17 to 54) years. The 24 patients were
      reviewed at a mean follow-up of 35 +/- 21 (range, 8 to 70) months. RESULTS: A
      total of 22/24 patients (91.6%) returned to activities at a mean time of 11.6 +/-
      3.87 (range, 8 to 24) weeks. Mean preoperative pain level was 6.2 +/- 1.4 and the
      pain level improved after treatment to a mean of 0.7 +/- 1. One patient developed
      a symptomatic hallux valgus deformity after the resection of the medial sesamoid.
      CONCLUSIONS: This case series demonstrates good results after sesamoidectomy for
      sesamoid fractures in athletic individuals with reliable pain relief and RTA
      within 11.6 weeks. Progressive hallux valgus remains a concern after medial
      sesamoidectomy, with an incidence of 1 in 24 cases in this study.

PMID- 22995256
TI  - Partial foot amputation in patients with diabetic foot ulcers.
AB  - BACKGROUND: Transtibial amputations (TTA) are performed for recalcitrant or
      infected ulcers of the midfoot, hindfoot, or ankle. This procedure results in
      decreased ambulatory status caused by increased oxygen demands and energy
      expenditure. Partial foot amputations have the advantage of being an end-bearing
      limb and require less work to walk, theoretically suggesting improved functional
      outcome. The purpose of this research was to examine the longevity, outcome, and
      mortality of partial foot amputations as an alternative to TTA. METHODS:
      Retrospective chart review identified diabetic patients with transmetatarsal,
      Chopart's, and calcanectomy amputations for osteomyelitis or nonhealing ulcers. A
      control group consisted of diabetic patients who underwent TTA. A comparison
      between groups examined mortality, proximal ipsilateral reamputation, and a
      validated ambulatory functional outcome measure. RESULTS: Eighteen TTA patients
      were enrolled. The 5-year mortality rate was 0.45, one patient required
      reamputation, and the mean postoperative ambulatory score was 2.8. Twenty-one
      transmetatarsal patients were enrolled. The 5-year mortality rate was 0.30, two
      patients required reamputation, and the mean postoperative ambulatory score was
      4.3. Ten Chopart's amputation patients were enrolled. The 5-year mortality rate
      was 0.36, six patients required reamputation, and the mean postoperative
      ambulatory score was 4.3. Seventeen partial calcanectomy patients were enrolled.
      The 5-year mortality rate was 0.69, six patients required reamputation, and the
      mean postoperative ambulatory score was 4.3. Sixteen total calcanectomy patients
      were enrolled. The 5-year mortality rate was 0.59, five patients required
      reamputation, and the mean postoperative ambulatory score was 3.3. CONCLUSION:
      TTA is associated with high morbidity and mortality, which suggests that the
      advantage of partial foot amputations should be investigated. Only
      transmetatarsal amputations at 1 and 3 years were statistically lower for
      mortality than TTA. Partial foot amputations at the other levels failed to show
      statistically improved survivorship. Transmetatarsal and Chopart's amputations
      had high ambulatory levels and the longest durability, which suggests that these
      amputations may provide some ambulatory advantage.

PMID- 22995257
TI  - Complications of suture button ankle syndesmosis stabilization with modifications
      of surgical technique.
AB  - BACKGROUND: The TightRope(r) is a relatively new device designed to stabilize
      ankle syndesmotic injuries. There are no studies evaluating the clinical
      effectiveness of this technique and few reports addressing complications and
      potential modifications to the surgical technique reported in this article.
      MATERIALS AND METHODS: A retrospective review of 102 cases of traumatic ankle
      syndesmotic stabilization using the TightRope device is presented. Patients were
      followed up for a median of 85 days after surgery. RESULTS: Eight patients
      subsequently had the TightRope removed. This was performed for four reasons:
      osteomyelitis surrounding the implant, painful aseptic osteolysis surrounding the
      implant, failed stabilization of the syndesmosis, and unexplained pain.
      CONCLUSIONS: On the basis of experience, the authors recommend meticulous
      attention during the surgical technique. To prevent skin irritation and stitch
      abscess formation leading to osteomyelitis, the FiberWire loop is best cut with a
      knife at least 1 cm beyond the knot, allowing the sharp end of the FiberWire to
      lay flat adjacent to the fibula. Painful aseptic osteolytic reaction to the
      TightRope necessitates removal. To prevent rediastasis, a small medial incision
      is recommended for endobutton positioning directly abutting the tibial cortex
      without soft tissue interposition. Inserting the TightRope through a fibula plate
      prevents lateral button pull-through and rediastasis.

PMID- 22995258
TI  - Efficacy of corticosteroid injection versus size of plantar interdigital neuroma.
AB  - BACKGROUND: The aim of this prospective study was to assess the effectiveness of
      a single ultrasound-guided steroid injection in the treatment of Morton's
      neuromas and whether the response to injection correlates with the size of the
      neuroma. METHODS: Forty-three patients with clinical features of Morton's neuroma
      underwent ultrasound scan assessment. Once the lesion was confirmed in the
      relevant web space, a single corticosteroid injection was given using 40 mg of
      methylprednisolone along with 1% lidocaine. All scans and injections were
      performed by a single musculoskeletal radiologist. Patients were divided into two
      groups on the basis of the size of the lesion measured on the scan. Group 1
      included patients with neuromas of 5 mm or less and group 2 patients had neuromas
      larger than 5 mm. A visual analog scale (VAS) for pain (scale 0 to 10), the
      American Orthopaedic Foot and Ankle Society (AOFAS) score, and the Johnson
      satisfaction scale were used to assess patients before injection and then at 6
      weeks, 6 months, and 12 months following the injection. Thirty-nine patients had
      confirmed neuromas. Group 1 (lesion <= 5 mm) included 17 patients (mean age, 30
      years) (7 males, 10 females) and group 2 (lesion >5 mm) had 22 patients (mean
      age, 33 years) (8 males, 14 females). RESULTS: VAS scores, AOFAS scores, and
      Johnson scale improved significantly in both groups at 6 weeks (p < .0001). At 6
      months postinjection, this improvement remained significant only in group 1 with
      all scores (p < . 001). At 12 months, there was no difference between both groups
      and outcome scores nearly approached preinjection scores. At the final review,
      two patients in group 1 and four patients in group 2 had severe recurrent
      symptoms and therefore underwent surgical excision of the neuroma after they
      rejected the offer for a repeat injection (p = 0.6). CONCLUSION: A single
      ultrasound-guided corticosteroid injection resulted in generally short-term pain
      relief for symptomatic Morton's neuromas. The effectiveness of the injection
      appears to be more significant and long-lasting for lesions smaller than 5 mm.

PMID- 22995259
TI  - Effect of three-dimensional computed tomography reconstructions on reliability.
AB  - BACKGROUND: This study evaluated the impact of three-dimensional (3D) volume
      rendering computed tomography (CT) reconstructions on the inter- and
      intraobserver reliability of six commonly used classification systems in the
      assessment of calcaneal fractures. METHODS: Four independent observers with
      different levels of clinical training evaluated 64 fractures according to the
      classifications of the Orthopaedic Trauma Association (OTA), Essex-Lopresti,
      Sanders, Crosby, Zwipp, and Regazzoni, using two-dimensional (2D) CT scans with
      multiplanar reconstructions and 3D volume-rendering reconstructions. RESULTS:
      Interobserver reliability was moderate for the OTA, Essex-Lopresti, Sanders,
      Crosby, and Regazzoni classifications with 2D CT scans and 3D CT reconstructions.
      The Zwipp classification was poor with 2D CT scans and improved to moderate with
      3D reconstructions. Intraobserver reliability with 2D CT scans was good for the
      Essex-Lopresti classification and moderate for the OTA, Sanders, Crosby, Zwipp,
      and Regazzoni classifications. After the addition of 3D reconstructions, all
      classifications showed moderate intraobserver reliability. CONCLUSION: According
      to the findings of this study, the additional use of 3D reconstructions is of
      minor value when used in conjunction with the classifications of the OTA,
      Sanders, Crosby, Regazzoni, and Essex-Lopresti. If calcaneal fractures are
      assessed with the Zwipp classification, 3D reconstructions could be used to
      achieve comparable reproducibility compared to other classifications. CLINICAL
      RELEVANCE: 3D reconstructions may have other benefits not evaluated in the
      presented study and may give useful information not captured by current
      classification systems.

PMID- 22995260
TI  - Vascularized pedicle bone grafting for nonunions of the tarsal navicular.
AB  - BACKGROUND: Osteonecrosis and nonunions of the tarsal navicular remain a
      challenging clinical problem. This article presents a series of patients treated
      with local vascularized pedicle bone grafting to the navicular. The purpose of
      this study was to determine the early clinical and radiographic outcomes of this
      technique. METHODS: Patients who underwent local vascularized pedicle bone
      grafting for osteonecrosis of the navicular from 2002 to 2007 were included in
      this study. The Ankle Osteoarthritis Scale (AOS), the Revised Foot Function Index
      (FFI-R), and the Short-Form 36 (SF-36) outcomes questionnaires were administered
      at most recent followup. Postoperative imaging was reviewed for evidence of
      healing. Eight patients with a mean age of 47.5 (range, 18 to 68) years were
      included in this study. The mean followup time was 61 (range, 32 to 72) months.
      RESULTS: Two patients underwent concomitant talonavicular arthrodesis. Two
      patients underwent additional procedures to address continued nonunion of the
      navicular. Neither patient elected to complete the outcomes questionnaires. The
      mean postoperative FFI score was 35.2 (range, 16.6 to 59). SF-36 subscales were
      as follows: bodily pain, 53; general health, 55; mental health, 75; physical
      function, 56; role emotional, 61; role physical, 37.5; social function, 71; and
      vitality, 56. The mean postoperative AOS pain score was 27.9 (range, 0 to 46.2)
      and the average disability score was 31.4 (range, 0 to 78.2). Postoperative
      imaging revealed consolidation and full healing in six of eight patients.
      CONCLUSION: Vascularized pedicle bone grafting is a treatment option for patients
      with chronic nonunion or osteonecrosis of the navicular. Additionally, it may
      serve as an adjunct procedure to provide increased vascularity to talonavicular
      arthrodesis in cases of navicular osteonecrosis and talonavicular arthritis.

PMID- 22995261
TI  - Comparative performance of ankle arthroscopy with and without traction.
AB  - BACKGROUND: Ankle arthroscopy has evolved as a diagnostic and therapeutic tool.
      Traditionally, it is performed with traction because of the tight ankle joint
      space. Original traction techniques were invasive but have progressed to the
      commonly used noninvasive modalities. Recent reports have suggested traction may
      be unnecessary. The purpose of this study was to compare prospectively ankle
      arthroscopy with and without traction in terms of ease of visualization of
      anatomic structures according to the Ferkel's ankle arthroscopy criteria.
      METHODS: Under Institutional Review Board approval, 103 patients received ankle
      arthroscopies, first with noninvasive traction and subsequently without traction.
      An independent observer scored each arthroscopy based on the 21-point Ferkel's
      criteria. For each structure adequately visualized, one point was given.
      Inadequate visualization was defined as excessive force or as visible cartilage
      scuffing. The maximum possible score was 21 points and the lowest was zero. Fifty
      five females and 48 males, average age 35 (range, 16 to 71) years, participated
      in the study. RESULTS: Noninvasive traction facilitated visualization of all
      structures of the anterior ankle in more than 90% of cases except for the
      anterior compartment and lateral gutters, which were better visualized without
      traction with the ankle in dorsiflexion. No difference was seen when visualizing
      the talus. Traction arthroscopy performed better when evaluating the central and
      posterior ankle. The mean score difference was statistically significant, 11.2
      versus 18.5 points, favoring noninvasive traction arthroscopy. The complication
      rate was 4%. CONCLUSION: Noninvasive traction facilitated complete ankle
      arthroscopy. Dorsiflexion improved visualization of the anterior compartment and
      lateral ankle gutter. The authors recommend noninvasive traction when performing
      ankle arthroscopy.

PMID- 22995262
TI  - Posterior approach with fibular preservation for tibiotalocalcaneal arthrodesis
      with an intramedullary nail.

PMID- 22995263
TI  - Gastrocnemius proximal release with minimal incision: a modified technique.

PMID- 22995264
TI  - Development of the Identification of Functional Ankle Instability (IdFAI).
AB  - BACKGROUND: Self-reported questionnaires are a common method used in identifying
      individuals with ankle instability. Recently a study illustrated the singular use
      of any of the most frequently utilized questionnaires failed to significantly
      predict ankle stability status. Therefore, the purpose of this article was to
      present information related to the development of the Identification of
      Functional Ankle Instability (IdFAI). METHODS: Volunteers (n = 278; 125 males,
      153 females, 19.8 +/- 1.4 years) completed the IdFAI on one occasion. An
      exploratory factor analysis was conducted with principal axis factoring as the
      extraction method with varimax rotation. Additionally, a discriminant function
      analysis was conducted to identify a discrimination score and to evaluate the
      accuracy of the questionnaire. RESULTS: The factor analysis revealed: factor 1
      (four questions) explained 53.7% of the variance, factor 2 (four questions) with
      an additional 17.4%, and factor 3 (two questions) an additional 6.3%. Overall,
      these factors accounted for 77.4% of the variance. There was a distinct
      discrimination score of 10.3 to identify people who have the minimally accepted
      criteria for FAI. Overall, the IdFAI has an accuracy of 89.6%. CONCLUSION: This
      investigation showed that the IdFAI was a feasible and appropriate way to
      identify individuals with FAI. CLINICAL RELEVANCE: We suggest clinicians and
      researchers utilize the IdFAI to identify individuals with functional ankle
      instability since it is a short, simple, easy questionnaire to administer and
      take, and has been shown to have excellent accuracy.

PMID- 22995265
TI  - Clinical tip: aiming probe for a precise medial malleolar osteotomy.

PMID- 22995266
TI  - Operative technique of two parallel compression screws and autologous bone graft
      for ankle arthrodesis after failed total ankle replacement.
AB  - BACKGROUND: The management of failed total ankle replacement (TAR) depends on the
      primary indication, presence of infection, condition of adjacent joints, and
      available bone stock. In addition, the patient's expectations, age, and general
      health should also be taken into account. METHODS: This article describes a
      technique of arthrodesis in failed TAR with two parallel screws inserted in
      opposite directions and autologous cancellous bone graft. Four patients were
      managed using this technique. The subtalar joint and both malleoli were
      preserved. RESULTS: The average time for radiological union was 14.8 weeks. There
      were no hardware-related complications or infections. One patient developed
      subsequent subtalar arthritis and is waiting for subtalar joint fusion.
      CONCLUSION: The results from this small series of patients suggest that
      arthrodesis following failed total ankle replacement with two parallel screws and
      bone graft may be an effective technique.

PMID- 22995267
TI  - Effect of heating on the mechanical properties of insole materials.
AB  - BACKGROUND: The most common method of customizing shoe insoles to the shape and
      surface of the foot is to heat and then mold the materials. The effect of heating
      on the mechanical properties of these materials is unknown. METHODS: The
      properties of individual and common combinations of insole materials were tested
      before and after heating. Individual materials tested were soft Plastazote (SP),
      medium Plastazote (MP), Puff (F), and Nickelplast (N); combinations of materials
      that were tested were SP + F and MP + F, each with and without Poron (P). Three
      samples of each were tested five times. Materials were heated and then compressed
      with an MTS servohydraulic device. Load transmission and percent compression at
      maximal load were measured on single materials and their combinations. Stress
      strain curves were measured. RESULTS: Compared to unheated material, the heated
      material transmitted higher forces. After heating, the combinations transmitted
      maximal load at a lower percentage of compression (i.e., became stiffer). Heating
      also changed the stress-strain curves of the three-material combinations, causing
      them to transmit maximal pressure at a lower strain. CONCLUSION: Heating insole
      materials changed their mechanical properties. The materials became stiffer and
      less effective in the attenuation of applied forces. CLINICAL RELEVANCE: The
      common practice of heating insole materials to improve their contact with the
      foot reduced the pressure-reducing properties of the materials, which may
      decrease their clinical effectiveness.

PMID- 22995268
TI  - Force and displacement measurements of the distal fibula during simulated ankle
      loading tests for high ankle sprains.
AB  - BACKGROUND: Syndesmosis (high ankle) sprains produce disruption of the distal
      tibiofibular ligaments. Forces on the distal fibula that produce these injuries
      are unknown. METHODS: Twenty-seven fresh-frozen lower extremities were used for
      this study. A load cell recorded forces acting on the distal fibula from forced
      ankle dorsiflexion and applied external foot torque; medial-lateral and anterior
      posterior displacements of the distal fibula were recorded. Fibular forces and
      axial displacements were also recorded with applied axial force. RESULTS: During
      forced ankle dorsiflexion and external foot torque tests, the distal fibula
      always displaced posteriorly with respect to the tibia with no measurable medial
      lateral displacement. With 10 Nm dorsiflexion moment, cutting the tibiofibular
      ligaments approximately doubled fibular force and displacement values. Cutting
      the tibiofibular ligaments significantly increased fibular displacement from
      applied external foot torque. Fibular forces and axial displacements from applied
      axial weight-bearing force were highest with the foot dorsiflexed. The highest
      mean fibular force in the study (271.9 N) occurred with 10 Nm external foot
      torque applied to a dorsiflexed foot under 1000 N axial force. CONCLUSIONS: Two
      important modes of loading that could produce high ankle sprains were identified:
      forced ankle dorsiflexion and external foot torque applied to a dorsiflexed ankle
      loaded with axial force. The distal tibiofibular ligaments restrained fibular
      displacement during these tests. CLINICAL RELEVANCE: Residual mortise widening
      observed at surgery may be the result of tibiofibular ligament injuries caused by
      posterior displacement of the fibula. Therefore, a syndesmosis screw used to fix
      the fibula would be subjected to posterior bending forces from these loading
      modes. Ankle bracing to prevent extreme ankle dorsiflexion during rehabilitation
      may be advisable to prevent excessive fibular motions that could affect
      syndesmosis healing.

PMID- 22995269
TI  - Topical review: barefoot running.

PMID- 22995270
TI  - Use of an inflatable pressure bag bump for medial and lateral operative
      approaches to the lower leg.

PMID- 22995271
TI  - Dorsal dislocation of the great toe in a professional football player: case
      report.

PMID- 22995272
TI  - Minimally invasive subtalar arthrodesis with iliac crest autograft through
      posterior arthroscopic portals: a technical note.

PMID- 22995273
TI  - FootForum: fee for service.

PMID- 22995274
TI  - Haglund's deformity.

PMID- 22995277
TI  - Different MUC1 gene polymorphisms in German and Japanese ethnicities affect serum
      KL-6 levels.
AB  - BACKGROUND: KL-6 is a high-molecular-weight glycoprotein classified as human
      Mucin-1 (MUC1). KL-6 has been reported to be a sensitive biomarker for
      interstitial lung diseases (ILDs) in the Japanese population. It is also known
      that polymorphisms in the MUC1 gene affect serum levels of KL-6. This study was
      conducted to evaluate serum levels of KL-6 and MUC1 polymorphisms in both German
      and Japanese populations. METHODS: Serum levels of KL-6 were measured in 267
      patients with ILDs (152 German and 115 Japanese) and 186 healthy subjects (HS)
      (76 German and 110 Japanese). In addition, rs4072037 single nucleotide
      polymorphisms (SNPs) were genotyped by polymerase chain reaction. The optimal
      cutoff values for discriminating patients with ILDs from HS was determined by
      receiver operating characteristic analysis based on ethnicity and rs4072037
      genotypes. RESULTS: The serum KL-6 levels in patients with ILDs were
      significantly higher compared with HS in both the German and the Japanese cohorts
      (both p<0.001). The discriminating cutoff value of serum KL-6 in the German
      cohort was significantly higher than the value in the Japanese cohort. The
      difference in the serum levels of KL-6 was significantly associated with the
      rs4072037 genotype distribution. CONCLUSIONS: Even in the German cohort, the
      serum KL6 levels were significantly higher in patients with ILDs than HS. Because
      of differences in the genotype distribution of rs4072037, the KL-6 cutoff value
      for the German cohort that discriminated patients with ILDs from HS was
      significantly higher than the value in the Japanese cohort.

PMID- 22995278
TI  - The evolution and putative function of phosducin-like proteins in the malaria
      parasite Plasmodium.
AB  - Ubiquitous to the proteomes of all living species is the presence of proteins
      containing the thioredoxin (Trx)-domain. The best characterized Trx-domain
      containing proteins include the enzymes involved in cellular redox metabolism
      facilitated by their cysteine-containing active site. But not all members of the
      Trx-fold superfamily exhibit this catalytic motif, e.g., the phosducin-like
      (PhLP) family of proteins. Genome sequencing efforts have uncovered new Trx
      domain containing proteins, and their redox activity and cellular functions have
      yet to be determined. The genome of the malaria parasite Plasmodium contains
      multiple thioredoxins and thioredoxin-like proteins which are of considerable
      interest given their role in the parasite's antioxidant defense. While
      adaptations within the Trx-domain have been studied, primarily with respect to
      redox active structures, PhLP proteins have not been examined. Using the
      uncharacterized phosducin-like protein from Plasmodium berghei PhLP-1, we
      investigated the evolution of PhLP proteins across all branches of the tree of
      life. As a result of our analysis, we have discovered the presence of two
      additional PhLP proteins in Plasmodium, PhLP-2 and PhLP-3. Sequence homology with
      annotated PhLP proteins in other species confirms that the Plasmodium PhLP-2 and
      PhLP-3 belong to the PhLP family of proteins. Furthermore, as a result of our
      analysis we hypothesize that the PhLP-2 thioredoxin was lost over time given its
      absence from higher-order eukaryotes. Probing deeper into the putative function
      of these proteins, inspection of the active sites indicate that PbPhLP-1 and
      PbPhLP-2 may be redox active while PbPhLP-3 is very likely not. The results of
      this phylogenetic study provide insight into the emergence of this family of Trx
      domain containing proteins.

PMID- 22995279
TI  - A variant in the promoter of MBL2 is associated with protection against visceral
      leishmaniasis in Morocco.
AB  - Progressive visceral leishmaniasis (VL) is fatal if not treated; yet, most
      infections with the causative agents are asymptomatic. We hypothesized that
      genetic factors contribute to this variable response to infection. The mannose
      binding lectin 2 gene (MBL2) is a candidate that merits examination in the
      context of VL because it enhances infection with intracellular pathogens. Four
      functional MBL2 polymorphisms at codons 52, 54, 57 and in the promoter at the 
      221 position (X/Y) are known to be associated with the outcome of several
      diseases. The aim of the present study was to investigate whether these
      functional variants were associated with VL in Moroccan children. Here, we
      genotyped polymorphisms by sequencing and PCR-RFLP in 112 individuals with VL, 97
      asymptomatic subjects and 42 healthy individuals who had no evidence of present
      or past infection. Regression analysis showed no significant association between
      polymorphisms in exon 1 genotypes and outcome of infection with Leishmania
      infantum. However, the genotype XY in -221 conferred a protective role against VL
      in our study population with a significant difference (OR=0.291; CI [0.158
      0.538]; p=0.0006). Subjects with YY genotypes in -221 had a higher risk to
      developing VL. We concluded that MBL2 polymorphism at the -221 promoter region
      plays a protective role in L. infantum infection.

PMID- 22995281
TI  - Whole genome sequence analysis of bovine G6P[11] rotavirus strain found in a
      child with gastroenteritis.
AB  - During the rotavirus strain surveillance in Slovenia, G6P[11] bovine rotavirus
      strain was detected in a 5 months old boy with gastroenteritis. The strain was
      enrolled in a whole genome sequence analysis to determine its genome segment
      composition and genetic characteristics. Genotype composition for the whole
      genome was G6-P[11]-I2-R2-C2-M2-A13-N2-T6-E2-H3, reflecting similarities with
      bovine rotavirus strains. The bovine origin of the strain was confirmed in all
      genome segments, showing the highest nucleotide identity with bovine rotavirus
      strains and clustering of the RVA/Human-wt/SVN/SI-R56/07/2007/G6P[11] together
      with bovine rotavirus strains in phylogenetic analysis. This is the first bovine
      G6P[11] rotavirus strain with the whole genome analysis and the first report on
      rotavirus G6P[11] genotype detected in humans.

PMID- 22995282
TI  - Spinal interaction between the highly selective MU agonist DAMGO and several
      delta opioid receptor ligands in naive and morphine-tolerant mice.
AB  - Since the discovery of opioid receptor dimers their possible roles in opioid
      actions were intensively investigated. Here we suggest a mechanism that may
      involve the MU-delta opioid heterodimers. The exact role of delta opioid
      receptors in antinociception and in the development of opioid tolerance is still
      unclear. While receptor up-regulation can be observed during the development of
      opioid tolerance no MU receptor down-regulation could be detected within five
      days. In our present work we investigated how the selective delta opioid receptor
      agonists and antagonists influence the antinociceptive effect of the selective MU
      receptor agonist DAMGO in naive and morphine-tolerant mice. We treated male NMRI
      mice with 200 MUmol/kg subcutaneous (s.c.) morphine twice daily for three days.
      On the fourth day we measured the antinociceptive effect of DAMGO alone and
      combined with delta ligands: DPDPE, deltorphin II (agonists), TIPP and TICPpsi
      (antagonists), respectively, administered intrathecally (i.t.) in mouse tail
      flick test. In naive control mice none of the delta ligands caused significant
      changes in the antinociceptive action of DAMGO. The treatment with s.c. morphine
      resulted in approximately four-fold tolerance to i.t. DAMGO, i.e. the ED50 value
      of DAMGO was four times as high as in naive mice. 500 and 1000 pmol/mouse of the
      delta1 selective agonist DPDPE enhanced the tolerance to DAMGO while 1000
      pmol/mouse of the delta2 selective agonist deltorphin II did not influence the
      degree of tolerance. However, both delta antagonists TIPP and TICPpsi potentiated
      the antinociceptive effect of i.t. DAMGO, thus they restored the potency of DAMGO
      to the control level. The inhibitory action of DPDPE against the antinociceptive
      effect of DAMGO could be antagonized by TIPP and TICPpsi. We hypothesize that
      during the development of morphine tolerance the formation of MUdelta
      heterodimers may contribute to the spinal opioid tolerance. delta ligands may
      affect the dimer formation differently. Those, like DPDPE may facilitate the
      dimer formation hence inhibit the antinociceptive effect of DAMGO by causing
      virtual MU receptor down-regulation. Ligands that do not affect the dimer
      formation do not influence antinociception either but ligands with the presumed
      capability of disconnecting the dimers may decrease the spinal tolerance to
      DAMGO.

PMID- 22995283
TI  - Probing the role of the sodium/calcium exchanger in pentylenetetrazole-induced
      generalized seizures in rats.
AB  - The Na+/Ca2+ exchanger (NCX) is thought to play an important role in the
      pathogenesis of pentylenetetrazole (PTZ)-induced tonic flexion in mice. Here, I
      investigated the expression of PTZ-induced generalized clonic and tonic-clonic
      seizures in rats, using two potent NCX reverse mode inhibitors, KB-R7943 and SN-6
      for NCX subtypes 3 (NCX3) and 1 (NCX1), respectively. Pretreatment with KB-R7943
      (3, 10, and 30 mg/kg; p.o.) significantly reduced the expression of PTZ-induced
      generalized seizures with clonic and tonic-clonic components in 12-62% and 25-62%
      of the treated animals, respectively. In the remaining animals that exhibited
      seizures, KB-R7943 (3 mg/kg; p.o.) pretreatment significantly delayed the onset
      of the first seizure episode and reduced the seizure severity. Following
      pretreatment with SN-6 (0.3, 1, 3, 10, and 30 mg/kg; p.o.), clonic and tonic
      clonic PTZ-induced generalized seizures were reduced in 25-50% and 38-63% of
      treated animals, respectively. SN-6 (0.3, 1, and 3 mg/kg; p.o.) also
      significantly reduced PTZ-induced seizure severity scores, but did not alter
      seizure latencies. KB-R7943 (3 and 30 mg/kg; p.o.) or SN-6 (3 and 30 mg/kg; p.o.)
      administration potentiated the sub-anticonvulsant dose of diazepam (2.5 mg/kg;
      i.p.) that suppresses clonic and tonic-clonic PTZ-induced seizures. These
      findings suggested that Ca2+ influx via the NCX in reverse mode contributes to a
      neuronal hyperexcitability that leads to clonic and tonic-clonic generalized
      seizures and that the NCX1 and NCX3 isoforms may serve as novel molecular targets
      for seizure suppression.

PMID- 22995285
TI  - A survey of dominant mutations in Arabidopsis thaliana.
AB  - Following the recent publication of a comprehensive dataset of 2400 genes with a
      loss-of-function mutant phenotype in Arabidopsis (Arabidopsis thaliana),
      questions remain concerning the diversity of dominant mutations in Arabidopsis.
      Most of these dominant phenotypes are expected to result from inappropriate gene
      expression, novel protein function, or disrupted protein complexes. This review
      highlights the major classes of dominant mutations observed in model organisms
      and presents a collection of 200 Arabidopsis genes associated with a dominant or
      semidominant phenotype. Emphasis is placed on mutants identified through forward
      genetic screens of mutagenized or activation-tagged populations. These datasets
      illustrate the variety of genetic changes and protein functions that underlie
      dominance in Arabidopsis and may ultimately contribute to phenotypic variation in
      flowering plants.

PMID- 22995284
TI  - Utility of the first few100 approach during the 2009 influenza A(H1N1) pandemic
      in the Netherlands.
AB  - BACKGROUND: To guide policy and control measures, decent scientific data are
      needed for a comprehensive assessment of epidemiological, clinical and
      virological characteristics of the First Few hundred (FF100) cases. We discuss
      the feasibility of the FF100 approach during the 2009 pandemic and the added
      value compared with alternative data sources available. METHODS: The pandemic
      preparedness plan enabled us to perform a case-control study, assessing patient
      characteristics and risk factors for experiencing symptomatic influenza
      A(H1N1)2009 infection and providing insight into transmission. We assessed to
      what extent timely and novel data were generated compared to other available data
      sources. RESULTS: In May-December 2009, a total of 68 cases and 48 controls were
      included in the study. Underlying non-respiratory diseases were significantly
      more common among cases compared to controls, while a protective effect was found
      for frequent hand washing. Seroconversion was found for 7/30 controls (23%), and
      persisting high titers for 4/30 controls (13%). The labour-intensive study design
      resulted in slow and restricted recruitment. CONCLUSIONS: The findings of our
      case-control study gave new insights in transmission risks and possible
      interventions for improved control. Nevertheless, the FF100 approach lacked
      timeliness and power due to limited recruitment. For future pandemics we suggest
      pooling data from several countries, to enable collecting sufficient data in a
      relatively short period.

PMID- 22995286
TI  - Assessing and improving health in the workplace: an integration of subjective and
      objective measures with the STress Assessment and Research Toolkit (St.A.R.T.)
      method.
AB  - BACKGROUND: The aim of this work was to introduce a new combined method of
      subjective and objective measures to assess psychosocial risk factors at work and
      improve workers' health and well-being. In the literature most of the research on
      work-related stress focuses on self-report measures and this work represents the
      first methodology capable of integrating different sources of data. METHOD: An
      integrated method entitled St.A.R.T. (STress Assessment and Research Toolkit) was
      used in order to assess psychosocial risk factors and two health outcomes. In
      particular, a self-report questionnaire combined with an observational structured
      checklist was administered to 113 workers from an Italian retail company.
      RESULTS: The data showed a correlation between subjective data and the rating
      data of the observational checklist for the psychosocial risk factors related to
      work contexts such as customer relationship management and customer queue.
      Conversely, the factors related to work content (workload and boredom) measured
      with different methods (subjective vs. objective) showed a discrepancy.
      Furthermore, subjective measures of psychosocial risk factors were more
      predictive of workers' psychological health and exhaustion than rating data. The
      different objective measures played different roles, however, in terms of their
      influence on the two health outcomes considered. CONCLUSIONS: It is important to
      integrate self-related assessment of stressors with objective measures for a
      better understanding of workers' conditions in the workplace. The method
      presented could be considered a useful methodology for combining the two measures
      and differentiating the impact of different psychological risk factors related to
      work content and context on workers' health.

PMID- 22995280
TI  - Hierarchical clustering of genetic diversity associated to different levels of
      mutation and recombination in Escherichia coli: a study based on Mexican
      isolates.
AB  - Escherichia coli occur as either free-living microorganisms, or within the colons
      of mammals and birds as pathogenic or commensal bacteria. Although the Mexican
      population of intestinal E. coli maintains high levels of genetic diversity, the
      exact mechanisms by which this occurs remain unknown. We therefore investigated
      the role of homologous recombination and point mutation in the genetic
      diversification and population structure of Mexican strains of E. coli. This was
      explored using a multi locus sequence typing (MLST) approach in a non-outbreak
      related, host-wide sample of 128 isolates. Overall, genetic diversification in
      this sample appears to be driven primarily by homologous recombination, and to a
      lesser extent, by point mutation. Since genetic diversity is hierarchically
      organized according to the MLST genealogy, we observed that there is not a
      homogeneous recombination rate, but that different rates emerge at different
      clustering levels such as phylogenetic group, lineage and clonal complex (CC).
      Moreover, we detected clear signature of substructure among the A+B1 phylogenetic
      group, where the majority of isolates were differentiated into four discrete
      lineages. Substructure pattern is revealed by the presence of several CCs
      associated to a particular life style and host as well as to different genetic
      diversification mechanisms. We propose these findings as an alternative
      explanation for the maintenance of the clear phylogenetic signal of this species
      despite the prevalence of homologous recombination. Finally, we corroborate using
      both phylogenetic and genetic population approaches as an effective mean to
      establish epidemiological surveillance tailored to the ecological specificities
      of each geographic region.

PMID- 22995287
TI  - Observation of fresh Bos indicus embryos comparing stereoscopic and phase
      contrast microscopy.
AB  - Summary The precision of embryo evaluation using stereoscopic microscopy (SM) and
      inverted phase contrast microscopy (PCM) was compared in 20 Bos indicus cows
      superovulated at two different times of the year. In total, 118 embryos were
      collected and classified according to their developmental stage and quality by
      two independent evaluators using SM and inverted PCM. Cohen's kappa coefficient
      was used to determine concordance between SM and PCM observations. A good level
      of agreement (k = 0.616) was found for quality level, and a moderate one (k =
      0.464) for developmental stage, particularly at the morula stage. Using the TUNEL
      (terminal deoxynucleotidyl transferase dUTP nick-end labelling) technique,
      concordance level was deemed to be low with the SM (k = 0.169), and poor with the
      PCM (k = 0.217). Differences in concordance levels were also found between
      observations made at the two times of year, 78 embryos were evaluated in the
      rainy season when concordance level was good (k = 0.68), in contrast to the 40
      embryos evaluated in the dry season when agreement was found to be poor (k =
      0.24). In conclusion, inverted PCM was somewhat more effective for evaluating
      embryos, particularly at the morula stage. However, considering the high cost of
      an inverted PCM, the differences observed do not justify its purchase for routine
      embryo evaluation. 

PMID- 22995288
TI  - Higher normal ranges of urine albumin-to-creatinine ratio are independently
      associated with carotid intima-media thickness.
AB  - BACKGROUND: High normal values of urine albumin-to-creatinine ratio (UACR) have
      been reported to have predictive values for hypertension, incident stroke, and
      higher mortality in the general population. This study aimed to investigate the
      association between normal ranges of UACR and carotid intima-media thickness
      (CIMT) in adult population. METHODS: We performed a cross-sectional study in
      adults aged 45 to 74 years who were living in Namwon City, South Korea. Both
      common CIMTs were measured, and mean values were calculated. Normal values of
      UACR were defined as <30mg/g and categorized into quintiles; less than 6.50, 6.51
      9.79, 9.80-13.49, 13.50-18.89, and more than 18.90 mg/g. The association between
      the quintiles of UACR and common CIMT was analyzed and stratified by sex.
      RESULTS: A total of 7555 participants (3084 men and 4471 women) with normal UACR
      were enrolled in the present study. Common CIMT was positively and independently
      associated with increasing quintiles of UACR in men and women, even after
      adjusting for potential confounders including age and cardiovascular risk
      factors. Compared to the first quintile, the fifth quintile showed odds ratios of
      1.80 (95% confidence intervals, 1.26-2.55) and 1.97 (1.28-3.04) for increased
      CIMT (>0.9mm) in men and women, respectively. CONCLUSION: Higher UACR values
      within normal ranges (<30 mg/g) were positively and independently associated with
      CIMT in a Korean general population, suggesting that higher normal values of UACR
      might be a risk marker of subclinical carotid atherosclerosis.

PMID- 22995289
TI  - [Epidemiological aspects of West Nile virus infection in Morocco].
AB  - Morocco has undergone three outbreaks of West Nile fever. The first, in 1996,
      began with a case in a horse herd in Benslimane (central region) and spread to
      neighboring cities (in the central and northwestern regions). The next two
      outbreaks appeared after identical 7-year epidemiological latency periods (in
      2003 and 2010) in the same area and season. The only human case, which was fatal,
      occurred during the 1996 outbreak. The West Nile virus strains circulating in
      Morocco are closely related to other western Mediterranean strains and are
      characterized by high virulence in horses.

PMID- 22995290
TI  - In vitro metabolism study of the promising anticancer agent the lignan (-)
      grandisin.
AB  - The lignan (-)-grandisin has shown important pharmacological activities, such as
      citotoxicity and antiangiogenic, antibacterial and trypanocidal activities. So,
      it has been considered as a potential drug candidate. In the early drug
      development process, drug metabolism is one of the main parameters that should be
      evaluated; therefore, the biotransformation of this lignan by rat liver
      microsomes was investigated for the first time. In order to perform the
      biotransformation study and to determine the kinetic parameters, a simple,
      sensitive and selective HPLC method was developed and fully validated. After
      method validation, the biotransformation study was accomplished and the kinetic
      parameters were determined. The biotransformation study obeyed the Michaelis
      Menten kinetics. The V(max) and K(m) were 1.46 +/- 0.034 MUmol/mg protein/h and
      8.99 +/- 0.488 MUM, respectively. In addition, the formation of dihydro
      grandisin, characterized by GC-MS, by mammalian systems indicated the involvement
      of a CYP450 enzyme type.

PMID- 22995291
TI  - A subset of circulating microRNAs are predictive for cardiac death after
      discharge for acute myocardial infarction.
AB  - To investigate the prognostic impact of circulating microRNAs (miRs) in patients
      who survived acute myocardial infarction (AMI), we compared the circulating miR
      signature at the time of survival discharge among samples in the serum bank of
      the Osaka Acute Coronary Insufficiency Study. Using a high-throughput array
      consisting of 667 miRs, 11 miRs were found to be differentially expressed in the
      serum among patients at high-risk for cardiac death. Real-time RT-PCR confirmed
      that the serum levels of miR-155 and miR-380* were approximately 4- and 3-fold
      higher, respectively, in patients who experienced cardiac death within 1 year
      after discharge. Accordingly, a subset of circulating miRs might be predictive
      for cardiac death in post-AMI patients.

PMID- 22995292
TI  - Cautious use of fli1a:EGFP transgenic zebrafish in vascular research.
AB  - Integration of exogenous sequence into an intact genome may cause some artificial
      phenotype or unspecific observations. We noticed that there is unspecific
      vascular expression when using fli1a:EGFP transgenic embryos for whole-mount in
      situ hybridization (WISH) experiments. We therefore tested whether the residual
      vector sequence contained in the fli1a:EGFP transgene or the integration of
      transgene into the genome may cause this expression 'noise' and/or deregulation
      of gene expression at a genome-wide level. RNA probes were synthesized using two
      different methods, i.e. vector-based and PCR-based. The vector-based dnmt3 probe
      showed unspecific vascular expression in fli1a:EGFP embryos, but not in wildtype
      embryos, by WISH. Moreover, we also found that compared to that in wildtype,
      there were alterations in gene expression at whole-genome level in the fli1a:EGFP
      embryos. Our finding that the vector sequence contained in the fli1a:EGFP genome
      causes unspecific vascular expression by WISH and the genome-wide expression
      profiling is altered in fli1a:EGFP embryos strongly argue that extra caution
      should be taken for data interpretation when using transgenics, such as
      fli1a:EGFP, in developmental biology studies.

PMID- 22995293
TI  - Constitutive internalization and recycling of metabotropic glutamate receptor 5
      (mGluR5).
AB  - Ligand-dependent and ligand-independent endocytic trafficking of G-protein
      coupled receptors (GPCRs) is critical for accurate receptor-mediated signaling
      and its regulation. Metabotropic glutamate receptor 5 (mGluR5) is a GPCR that
      plays a crucial role in circuit formation in the brain and also in various forms
      of synaptic plasticity including learning and memory. Outside the central nervous
      system this receptor also plays very important role in various other non-neuronal
      cells like heart cells, skin cells, hepatocytes, etc. Although the ligand
      mediated endocytosis of mGluR5 has been studied in some detail, ligand
      independent/constitutive endocytosis of the receptor has not been properly
      studied. Here, we have investigated the constitutive endocytosis of mGluR5 and
      also the sub-cellular fate of the receptor subsequent to internalization. We show
      here that mGluR5 undergoes constitutive internalization in HEK293 cells.
      Following endocytosis, the receptor enters the recycling compartment and no
      localization of the receptor was observed in the lysosome. In addition, we also
      report here that most of the receptors recycle to the cell surface subsequent to
      constitutive internalization. Thus, our data demonstrate that mGluR5 receptors
      internalize without the application of ligand and the internalized receptors
      recycle back to the cell surface following constitutive endocytosis.

PMID- 22995294
TI  - Cloning and functional expression of secreted phospholipases A(2) from Bothrops
      diporus (Yarara Chica).
AB  - Bothrops diporus is a very common viper in Argentina. At present, no complete
      sequence of secreted phospholipase A(2) (sPLA(2)) from this snake has been
      reported. We have cloned two sPLA(2) isoenzymes as well as a putative sPLA(2)
      like myotoxin from venom gland. The two sPLA(2) were expressed as inclusion
      bodies in Escherichia coli with an N-terminal tag of ubiquitin. After in vitro
      renaturation and cleavage step, using an ubiquitin specific peptidase, the
      recombinants exhibited sPLA(2) activity when analyzed by means of Langmuir
      dilauroylphosphatidylcholine monolayers as substrate. Both enzymes have a similar
      surface pressure-activity profile when compared with non-recombinant purified
      isoforms. To our knowledge, this is the first time that analysis of optimal
      lateral pressure of substrate monolayers by using the surface barostat technique
      is performed on recombinant sPLA(2)s.

PMID- 22995295
TI  - Febuxostat suppressed renal ischemia-reperfusion injury via reduced oxidative
      stress.
AB  - Febuxostat is a novel selective inhibitor of xanthine oxidase (XO), approved for
      treating hyperuricemia. XO inhibits the generation of uric acid (UA) as well as
      the resulting generation of superoxide. During renal ischemia-reperfusion (I/R)
      injury, the burst of reactive oxygen species (ROS) can trigger the inflammation
      and the tubular cell injury. As XO is a critical source of ROS, inhibition of XO
      could be a therapeutic target for I/R injury. Therefore, we performed this study
      to test the therapeutic effect of febuxostat on renal I/R injury. Sprague-Dawley
      rats, received vehicle or febuxostat, were subjected to right nephrectomy and
      left renal I/R injury. Febuxostat significantly suppressed XO activity, and
      thereby reduced oxidative stress, assessed by nitrotyrosine, thiobarbituric acid
      reactive substances (TBARS) and urine 8-isoprostane. Furthermore, febuxostat
      reduced the induction of endoplasmic reticulum (ER) stress, assessed by GRP-78,
      ATF4, and CHOP. Vehicle-treated I/R injured rats exhibited elevated serum
      creatinine and UN, which were significantly suppressed in febuxostat-treated I/R
      injured rats. Histological analysis revealed that fubuxostat-treated rats showed
      less tubular injury and interstitial fibrosis with reduction in ED1-positive
      macrophage infiltration, TUNEL positive apoptotic tubular cells, and interstitial
      smooth muscle alpha actin (SMalphaA) expression, compared to vehicle-treated
      rats. In conclusion; novel XO inhibitor, febuxostat, can protect kidney from
      renal I/R injury, and may contribute to preserve kidney function.

PMID- 22995296
TI  - Susceptibility of CD24(+) ovarian cancer cells to anti-cancer drugs and natural
      killer cells.
AB  - Natural killer cells are lymphocytes of the innate immune system that play a key
      role in the direct elimination of transformed or virus-infected cells. Recently,
      it has been reported that NK cells can attack cancer cells with stem cell-like
      properties. In this study, we isolated ovarian cancer cell lines CAOV3 and TOV21G
      with and without CD24, which has been reported as an ovarian cancer stem cell
      marker, and compared their drug resistance and susceptibility to NK cell lysis.
      The isolated CD24(+) CAOV3 and TOV21G cells were more resistant to cisplatin and
      doxorubicin anti-cancer drugs. Also, CD24(+) CAOV3 and TOV21G cells were more
      susceptible to NK cell lysis compared with CD24(-) cells. In order to identify
      reasons for the differing NK cell susceptibility, we examined NK cell-killing
      mechanisms against CD24(+) cancer cell lines by analyzing NKG2D ligands, MHC
      class I molecules, and natural cytotoxic receptor ligands expression on target
      cells. Consistently, CD24(+) CAOV3 and TOV21G cells showed up-regulated NKG2D
      ligands and down-regulated MHC class I molecule expression. These findings show
      that CD24(+) ovarian cancer cell lines are more resistant to antitumor drugs but
      are more susceptible to NK cell lysis; thus, NK cell immunotherapy might be
      useful in eliminating ovarian cancer stem cells and preventing tumor recurrence
      and metastasis.

PMID- 22995297
TI  - miR-1297 mediates PTEN expression and contributes to cell progression in LSCC.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression after
      transcription, and are involved in cancer development. Laryngeal squamous cell
      carcinoma (LSCC) is one of the most common malignant neoplasms with increasing
      incidence in recent years. In this paper, we report the overexpression of miR
      1297 in LSCC and Hep-2 cells. In addition, PTEN was identified to be directly
      regulated by miR-1297 through western blot and luciferase activity assay.
      Furthermore, downregulation of miR-1297 in Hep-2 cells was shown to inhibit
      cancer cell proliferation, migration, and tumor genesis. Our results document a
      new epigenetic mechanism for PTEN regulation in LSCC, which is crucial for the
      development of these tumors.

PMID- 22995298
TI  - Analyzing actin dynamics during the activation of the B cell receptor in live B
      cells.
AB  - Actin reorganization has been shown to be important for lymphocyte activation in
      response to antigenic stimulation. However, methods for quantitative analysis of
      actin dynamics in live lymphocytes are still underdeveloped. In this study, we
      describe new methods to examine the actin dynamics in B cells induced by
      antigenic stimulation. Using the A20 B cell line expressing GFP-actin, we
      analyzed in real time the redistribution of F-actin and the lateral mobility of
      actin flow in the surface of B cells in response to soluble and/or membrane
      associated antigens. Using fluorescently labeled G-actin, we identified the
      subcellular location and quantified the level of de novo actin polymerization
      sites in primary B cells. Using A20 B cells expressing G-actin fused with the
      photoconvertible protein mEos, we examined the kinetics of actin polymerization
      and depolymerization at the same time. Our studies present a set of methods that
      are capable of quantitatively analyzing the role of actin dynamics in lymphocyte
      activation.

PMID- 22995299
TI  - Protein expression and isotopic enrichment based on induction of the Entner
      Doudoroff pathway in Escherichia coli.
AB  - The Entner-Doudoroff pathway is known to exist in many organisms including
      bacteria, archea and eukarya. Although the common route for carbon catabolism in
      Escherichia coli is the Embden-Meyerhof-Parnas pathway, it was shown that
      gluconate catabolism in E. coli occurs via the Entner-Doudoroff pathway. We
      demonstrate here that by supplying BL21(DE3) competent E.coli cells with
      gluconate in a minimal growth medium, protein expression can be induced. Nuclear
      magnetic resonance data of over-expressed ubiquitin show that by using [1-(13)C]
      gluconate as the only carbon source, and (15)N-enriched ammonium chloride, sparse
      isotopic enrichment in the form of a spin-pair carbonyl-amide backbone enrichment
      is obtained. The specific amino acid labeling pattern is analyzed and is shown to
      be compatible with Entner-Doudoroff metabolism. Isotopic enrichment serves as a
      key factor in the biophysical characterization of proteins by various methods
      including nuclear magnetic resonance, mass spectrometry, infrared spectroscopy
      and more. Therefore, the method presented here can be applied to study proteins
      by obtaining sparse enrichment schemes that are not based on the regular
      glycolytic pathway, or to study the Entner-Doudoroff metabolism during protein
      expression.

PMID- 22995300
TI  - A proteomic analysis of Arabidopsis thaliana seedling responses to 3-oxo-octanoyl
      homoserine lactone, a bacterial quorum-sensing signal.
AB  - N-acyl-homoserine lactones (AHLs) are a class of bacterial quorum-sensing (QS)
      signals that are commonly used by Gram-negative bacteria for cell-to-cell
      communication. Recently, it has become evident that AHLs can regulate plant root
      growth and trigger plant defense responses; however, little is known about the
      plant response mechanisms to bacterial QS signals. In this study, we used a
      proteomic approach to investigate the responses of Arabidopsis thaliana seedlings
      to N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL), a bacterial QS signal. The
      results revealed that the abundance of 53 protein spots was significantly
      altered; two thirds of these proteins were found to be up-regulated after 3OC8
      HSL treatment. Thirty-four proteins were identified using MALDI-TOF-MS. These
      3OC8-HSL-responsive proteins, in addition to one protein of unknown function, are
      implicated in a variety of physiological processes, including metabolism of
      carbohydrate and energy, protein biosynthesis and quality control systems,
      defense response and signal transduction and cytoskeleton remodeling. Our
      bioinformatic analysis indicated that the chloroplasts are the intracellular
      organelles most influenced by the exposure to 3OC8-HSL. Our data indicate that
      plants have an extensive range of functional responses to bacterial AHLs that may
      play important roles in the interaction between plants and bacteria.

PMID- 22995301
TI  - Poly(propylene imine) dendrimers modified with maltose or maltotriose protect
      phosphorothioate oligodeoxynucleotides against nuclease activity.
AB  - The antisense oligonucleotides are promising agents for application in anti-HIV
      therapies. The antiretroviral nucleoside analogues administrated into circulatory
      system are vulnerable to nuclease degradation and require a vehicle which would
      not only facilitate therapeutic nucleotides into host cells, but would also
      provide protection against enzymatic degradation. Such potential is exhibited by
      poly(propylene imine) dendrimers - the branched cationic polymers easily
      interacting with oligonucleotides to form complexes called "dendriplexes". The
      aim of the present study was to evaluate the abilities of the fourth generation
      poly(propylene imine) dendrimers partially modified with maltose (PPI-Mal G4) or
      maltotriose (PPI-Mal-III G4) to protect anti-HIV antisense oligonucleotides
      (ODNs) from nucleolytic degradation. The ODNs (AT, GEM91, SREV) were complexed
      with dendrimers and subjected to cleavage by serum nucleases or endonuclease S1.
      The results showed that all examined dendrimers protected ODNs against nucleases
      contained in FBS. Both PPI-Mal G4 and PPI-Mal-III G4 dendrimers completely
      prevented ODNs digestion by nuclease S1 at neutral pH. The protective
      capabilities of investigated dendrimers were significantly weaker in acidic
      environment. The time stability assay showed that the dendriplexes formed by AT,
      GEM91, SREV and carbohydrate-modified PPI G4 dendrimers still existed after 12h
      incubation both in low and at neutral pH buffers. The conformational change of
      dendriplexes in acidic environment was proposed as possible phenomenon leading to
      exposition of ODNs to nuclease attack and significantly diminishing dendriplexes'
      resistance to nucleolitic digestion.

PMID- 22995302
TI  - SIRT1 inactivation induces inflammation through the dysregulation of autophagy in
      human THP-1 cells.
AB  - Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are
      some of the cells involved in the inflammatory process in atherogenesis.
      Autophagy exerts a protective effect against cellular stresses like inflammation,
      and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway
      includes SIRT1, a NAD(+)-dependent histone deacetylase, which is implicated in
      the regulation of a variety of cellular processes including inflammation and
      autophagy. The mechanism through which the dysfunction of SIRT1 contributes to
      the regulation of inflammation in relation to autophagy in monocytes/macrophages
      is unclear. In the present study, we demonstrate that treatment with 2-[(2
      Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a
      chemical inhibitor of SIRT1, induces the overexpression of inflammation-related
      genes such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 through
      nuclear factor (NF)-kappaB signaling activation, which is associated with
      autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased
      expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3
      methyladenine, also induces inflammation-related NF-kappaB activation. In
      p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-kappaB
      activation is blocked. In addition, inhibition of SIRT1 is involved in the
      activation of the mammalian target of rapamycin (mTOR) pathway and is implicated
      in decreased 5'-AMP activated kinase (AMPK) activation, leading to the impairment
      of autophagy. The mTOR inhibitor, rapamycin, abolishes Sirtinol-induced
      inflammation and NF-kappaB activation associated with p62/Sqstm1 accumulation. In
      summary, SIRT1 inactivation induces inflammation through NF-kappaB activation and
      dysregulates autophagy via nutrient-sensing pathways such as the mTOR and AMPK
      pathways, in THP-1 cells.

PMID- 22995303
TI  - Targeting SMARCAL1 as a novel strategy for cancer therapy.
AB  - SMARCAL1 is a SNF2 chromatin-remodeling protein with ATP-dependent annealing
      helicase activity. Recent studies have shown that SMARCAL1 is involved in DNA
      damage repair and cell cycle progression. Deficiency of SMARCAL1 enhances the
      anticancer activity of chemotherapy agents and reverses cancer cell resistance to
      these agents. Therefore, targeting SMARCAL1 is an attractive therapeutic approach
      for cancers with defects in DNA damage repair or cell cycle checkpoints. Here, we
      review advances in our understanding of the biochemical and cellular functions of
      SMARCAL1 made over the recent years and discuss the rationale for development of
      SMARCAL1 inhibitors as novel anticancer therapies.

PMID- 22995304
TI  - TLS-CHOP represses miR-486 expression, inducing upregulation of a metastasis
      regulator PAI-1 in human myxoid liposarcoma.
AB  - Myxoid liposarcomas (MLSs) are characterized by t(12;16)(q13;p11) translocation
      and expression of TLS-CHOP chimeric oncoprotein. However, the molecular functions
      of TLS-CHOP have not been fully understood. On the other hand, microRNAs (miRNAs)
      comprise an abundant class of endogenous small non-coding RNAs that negatively
      regulate the expression of their target genes, and are involved in many
      biological processes. It is now evident that dysregulation of miRNAs is an
      important step in the development of many cancers. To our knowledge, however,
      there have been no reports of the miRNAs involved in MLS tumorigenesis and
      development. In this study, we have found that miR-486 expression was repressed
      in TLS-CHOP-expressed NIH3T3 fibroblasts and MLS tissues, and exogenous
      overexpression of miR-486 repressed growth of MLS cells. Thus, downregulation of
      miR-486 may be an important process for MLS. In addition, we have identified
      plasminogen activator inhibitor-1 (PAI-1) as a novel target gene of miR-486. PAI
      1 is a unique type of serine protease inhibitor and is known to be one of the key
      regulators of tumor invasion and metastasis. Furthermore, knockdown of PAI-1 by a
      specific small interfering RNA (siRNA) inhibited growth of MLS cells, suggesting
      that increased expression of PAI-1 by miR-486 repression is critical for survival
      of MLS cells. Collectively, these results suggest a novel essential molecular
      mechanism that TLS-CHOP activates PAI-1 expression by repression of miR-486
      expression in MLS tumorigenesis and development.

PMID- 22995305
TI  - Altered allosteric regulation of muscle 6-phosphofructokinase causes Tarui
      disease.
AB  - Tarui disease is a glycogen storage disease (GSD VII) and characterized by
      exercise intolerance with muscle weakness and cramping, mild myopathy,
      myoglobinuria and compensated hemolysis. It is caused by mutations in the muscle
      6-phosphofructokinase (Pfk). Pfk is an oligomeric, allosteric enzyme which
      catalyzes one of the rate-limiting steps of the glycolysis: the phosphorylation
      of fructose 6-phosphate at position 1. Pfk activity is modulated by a number of
      regulators including adenine nucleotides. Recent crystal structures from
      eukaryotic Pfk displayed several allosteric adenine nucleotide binding sites.
      Functional studies revealed a reciprocal linkage between the activating and
      inhibitory allosteric binding sites. Herein, we showed that Asp(543)Ala, a
      naturally occurring disease-causing mutation in the activating binding site,
      causes an increased efficacy of ATP at the inhibitory allosteric binding site.
      The reciprocal linkage between the activating and inhibitory binding sites leads
      to reduced enzyme activity and therefore to the clinical phenotype.
      Pharmacological blockage of the inhibitory allosteric binding site or highly
      efficient ligands for the activating allosteric binding site may be of
      therapeutic relevance for patients with Tarui disease.

PMID- 22995307
TI  - Reduction of the immunostainable length of the hippocampal dentate granule cells'
      primary cilia in 3xAD-transgenic mice producing human Abeta(1-42) and tau.
AB  - The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis
      in adult rodents and humans. Virtually all dentate granule cells have a single
      immobile cilium with a microtubule spine or axoneme covered with a specialized
      cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3),
      and the p75 neurotrophin receptor (p75(NTR)). The signals from these receptors
      have been reported to stimulate neuroprogenitor proliferation and the post
      mitotic maturation of newborn granule cells into functioning granule cells. We
      have found that in 6-24-months-old triple transgenic Alzheimer's disease model
      mice (3xTg-AD) producing both Abeta(1-42) and the mutant human tau protein
      tau(P301L,) the dentate granule cells still had immunostainable SSTR3- and
      p75(NTR)-bearing cilia but they were only half the length of the immunostained
      cilia in the corresponding wild-type mice. However, the immunostainable length of
      the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large
      amounts of Abeta(1-42) or in mice accumulating only a mutant human tau protein.
      Thus it appears that a combination of Abeta(1-42) and tau protein accumulation
      affects the levels of functionally important receptors in 3xTg-AD mice. These
      observations raise the important possibility that structural and functional
      changes in granule cell cilia might have a role in AD.

PMID- 22995306
TI  - Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth
      muscle cell proliferation by suppressing PDGF receptor signaling.
AB  - Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper
      longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory,
      and anti-cancer properties; however, the role of PL in prevention of
      atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL
      in an in vivo murine model of accelerated atherosclerosis and defined its
      mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro.
      Local treatment with PL significantly reduced atherosclerotic plaque formation as
      well as proliferation and nuclear factor-kappa B (NF-kappaB) activation in an in
      vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and
      platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo
      findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor
      beta activation and suppressed downstream signaling molecules such as
      phospholipase Cgamma1, extracellular signal-regulated kinases 1 and 2 and Akt.
      Lastly, PL significantly attenuated activation of NF-kappaB-a downstream
      transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB
      stimulation. In conclusion, our findings demonstrate a novel, therapeutic
      mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

PMID- 22995308
TI  - Critical selection of internal control genes for quantitative real-time RT-PCR
      studies in lipopolysaccharide-stimulated human THP-1 and K562 cells.
AB  - The choice of internal control genes is important since it may affect the study
      outcome in RT-qPCR. Indeed, it is well-known that expression levels of
      traditional internal control genes can vary across tissue types and across
      experimental settings within one specific tissue type. The aim of this study is
      an evaluation of a set of housekeeping genes (HKGs) to be used in the
      normalization of gene expression in vitro different cultured cells, THP-1 and
      K562. The transcriptional stability of eleven potential internal control genes
      (RPL37A, ACTB, GAPDH, B(2)M, PPIB, PGK1, PPIA, SDHA, TBP, HPRT1 and RPL13A) were
      evaluated using RT-qPCR and were compared in different treatment, that was un
      stimulated or LPS-stimulated cells. The raw Ct values were determined for each
      candidate gene at different time points following LPS-stimulated or unstimulated
      cells. Furthermore, all data were analyzed by the geNorm, BestKeeper, and
      NormFinder validation programs. Results indicated that PPIB and PGK1 were the
      most stable internal control genes in this study. RPL13A was found to be the
      least stable. This study provides the comprehensive reported assessment of
      internal control genes for use in expression studies in vitro cultured cells.
      These findings further emphasize the need to accurately validate candidate
      internal control genes in the study before use in gene expression studies using
      RT-qPCR.

PMID- 22995309
TI  - Inhibition of cell proliferation by a selective inhibitor of the Ca(2+)-activated
      Cl(-) channel, Ano1.
AB  - BACKGROUND: Ion channels play important roles in regulation of cellular
      proliferation. Ano1 (TMEM16A) is a Ca(2+)-activated Cl(-) channel expressed in
      several tumors and cell types. In the muscle layers of the gastrointestinal tract
      Ano1 is selectively expressed in interstitial cells of Cajal (ICC) and appears to
      be required for normal gastrointestinal slow wave electrical activity. However,
      Ano1 is expressed in all classes of ICC, including those that do not generate
      slow waves suggesting that Ano1 may have other functions. Indeed, a role for Ano1
      in regulating proliferation of tumors and ICC has been recently suggested.
      Recently, a high-throughput screen identified a small molecule, T16A(inh)-A01 as
      a specific inhibitor of Ano1. AIM: To investigate the effect of the T16A(inh)-A01
      inhibitor on proliferation in ICC and in the Ano1-expressing human pancreatic
      cancer cell line CFPAC-1. METHODS: Inhibition of Ano1 was demonstrated by whole
      cell voltage clamp recordings of currents in cells transfected with full-length
      human Ano1. The effect of T16A(inh)-A01 on ICC proliferation was examined in situ
      in organotypic cultures of intact mouse small intestinal smooth muscle strips and
      in primary cell cultures prepared from these tissues. ICC were identified by Kit
      immunoreactivity. Proliferating ICC and CFPAC-1 cells were identified by
      immunoreactivity for the nuclear antigen Ki67 or EdU incorporation, respectively.
      RESULTS: T16A(inh)-A01 inhibited Ca(2+)-activated Cl(-) currents by 60% at 10MUM
      in a voltage-independent fashion. Proliferation of ICC was significantly reduced
      in primary cultures from BALB/c mice following treatment with T16A(inh)-A01.
      Proliferation of the CFPAC-1 human cell-line was also reduced by T16A(inh)-A01.
      In organotypic cultures of smooth muscle strips from mouse jejunum, the
      proliferation of ICC was reduced but the total number of proliferating
      cells/confocal stack was not affected, suggesting that the inhibitory effect was
      specific for ICC. CONCLUSIONS: The selective Ano1 inhibitor T16A(inh)-A01
      inhibited Ca(2+)-activated Cl(-) currents, reduced the number of proliferating
      ICC in culture and inhibited proliferation in the pancreatic cancer cell line
      CFPAC-1. These data support the notion that chloride channels in general and Ano1
      in particular are involved in the regulation of proliferation.

PMID- 22995310
TI  - Crystal structures of arginine kinase in complex with ADP, nitrate, and various
      phosphagen analogs.
AB  - Arginine kinase catalyzes the reversible transfer of a phosphoryl group between
      ATP and l-arginine and is a monomeric homolog of the human enzyme creatine
      kinase. Arginine and creatine kinases belongs to the phosphagen kinase family of
      enzymes, which consists of eight known members, each of which is specific for its
      own phosphagen. Here, the source of phosphagen specificity in arginine kinase is
      investigated through the use of phosphagen analogs. Crystal structures have been
      determined for Limulus polyphemus arginine kinase with one of four arginine
      analogs bound in a transition state analog complex: l-ornithine, l-citrulline,
      imino-l-ornithine, and d-arginine. In all complexes, the enzyme achieves a closed
      conformation very similar to that of the cognate transition state analog complex,
      but differences are observed in the configurations of bound ligands. Arginine
      kinase exhibits no detectable activity towards ornithine, citrulline, or imino-l
      ornithine, and only trace activity towards d-arginine. The crystal structures
      presented here demonstrate that phosphagen specificity is derived neither from a
      lock-and-key mechanism nor a modulation of induced-fit conformational changes,
      but potentially from subtle distortions in bound substrate configurations.

PMID- 22995311
TI  - Functional cloning of Vibrio parahaemolyticus type III secretion system 1 in
      Escherichia coli K-12 strain as a molecular syringe.
AB  - The type III secretion system (T3SS) of gram-negative bacteria involves dedicated
      protein translocation machinery that directly injects proteins into target cells.
      Pathogenic bacteria already benefit from this unique system. The successful
      functional cloning of this useful tool into non-pathogenic bacteria would help
      establish novel clinical and basic biotechnology strategies in areas such as
      vaccine administration, the development of screening systems for anti-T3SS drugs
      and the target-specific delivery of bioactive compounds. In this study, we
      successfully cloned the Vibrio parahaemolyticus T3SS1 genetic locus into a non
      pathogenic Escherichia coli K-12 strain. Assays performed here revealed that the
      T3SS1 cloned into the E. coli K-12 strain has the ability to translocate V.
      parahaemolyticus T3SS1 secreted proteins. Importantly, we also observed this
      system to allow the E. coli K-12 strain to inject foreign protein, as well as the
      V. parahaemolyticus T3SS effector, into cultured cells. These results demonstrate
      a prospective useful tool with experimental and therapeutic applications.

PMID- 22995312
TI  - Identification of structural traits that increase the antimicrobial activity of a
      chimeric peptide of human beta-defensins 2 and 3.
AB  - Antimicrobial peptides participate in the first line of defence of many organisms
      against pathogens. In humans, the family of beta-defensins plays a pivotal role
      in innate immunity. Two human beta-defensins, beta-defensin-2 and -3 (HBD2 and
      HBD3), show substantial sequence identity and structural similarity. However,
      HBD3 kills Staphylococcus (S.) aureus with a 4- to 8-fold higher efficiency
      compared to HBD2, whereas their activities against Escherichia (E.) coli are very
      similar. The generation of six HBD2/HBD3-chimeric molecules led to the
      identification of distinct molecular regions which mediate their divergent
      killing properties. One of the chimeras (chimera C3) killed both E. coli and S.
      aureus with an even higher efficacy compared to the wild-type molecules. Due to
      the broad spectrum of its antimicrobial activity against many human multidrug
      resistant pathogens, this HBD2/HBD3-chimeric peptide represents a promising
      candidate for a new class of antibiotics. In order to investigate the structural
      basis of its exceptional antimicrobial activity, the peptide's tertiary structure
      was determined by NMR spectroscopy, which allowed its direct comparison to the
      published structures of HBD2 and HBD3 and the identification of the activity
      increasing molecular features.

PMID- 22995313
TI  - Letter to the editor on "Profiling molecular changes induced by hydrogen
      treatment of lung allografts prior to procurement".

PMID- 22995314
TI  - Role of RNA-binding protein tristetraprolin in tumor necrosis factor-alpha
      mediated gene expression.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the
      pathogenesis of inflammatory diseases. Excessive TNF-alpha expression induces
      tristetraprolin (TTP), an RNA-binding protein that regulates mRNA degradation,
      which in turn downregulates TNF and its downstream genes, thus resulting in anti
      inflammatory effects. In order to better understand the TNF-alpha mediated
      molecular pathways in inflammatory diseases, embryonic fibroblast (MEF) cell
      lines derived from TTP-deficient (KO) or wild type (WT) mice were treated with
      TNF-alpha and gene expression differences between two cell lines were compared by
      a microarray essay of 9224 genes. We found that TTP-KO cells had higher
      expression levels of pro-inflammatory genes than TTP-WT cells, and inflammatory
      genes were differentially regulated by TNF-alpha between TTP-KO and TTP-WT cells.
      Through a study of 2-dimentional gene set matrix analysis, we also found the
      genes upregulated by TNF-alpha in TTP KO cells were correlated with the
      pathologic phenotypes in inflammation, joint, or bone diseases. Our study
      provided a detailed genetic roadmap for further understanding the regulatory
      effect of TTP in inflammatory pathways related to human diseases.

PMID- 22995315
TI  - beta-Adrenergic receptor signaling increases NAADP and cADPR levels in the heart.
AB  - Evidence suggests that beta-Adrenergic receptor signaling increases heart rate
      and force through not just cyclic AMP but also the Ca(2+)-releasing second
      messengers NAADP (nicotinic acid adenine dinucleotide phosphate) and cADPR
      (cyclic ADP-ribose). Nevertheless, proof of the physiological relevance of these
      messengers requires direct measurements of their levels in response to receptor
      stimulation. Here we report that in intact Langendorff-perfused hearts beta
      adrenergic stimulation increased both messengers, with NAADP being transient and
      cADPR being sustained. Both NAADP and cADPR have physiological and therefore
      pathological relevance by providing alternative drug targets in the beta
      adrenergic receptor signaling pathway.

PMID- 22995316
TI  - Molecular signatures in response to Isoliquiritigenin in lymphoblastoid cell
      lines.
AB  - Isoliquiritigenin (ISL) has been known to induce cell cycle arrest and apoptosis
      of various cancer cells. However, genetic factors regulating ISL effects remain
      unclear. The aim of this study was to identify the molecular signatures involved
      in ISL-induced cell death of EBV-transformed lymphoblastoid cell lines (LCLs)
      using microarray analyses. For gene expression and microRNA (miRNA) microarray
      experiments, each of 12 LCL strains was independently treated with ISL or DMSO as
      a vehicle control for a day prior to total RNA extraction. ISL treatment
      inhibited cell proliferation of LCLs in a dose-dependent manner. Microarray
      analysis showed that ISL-treated LCLs represented gene expression changes in cell
      cycle and p53 signaling pathway, having a potential as regulators in LCL survival
      and sensitivity to ISL-induced cytotoxicity. In addition, 36 miRNAs including
      five miRNAs with unknown functions were differentially expressed in ISL-treated
      LCLs. The integrative analysis of miRNA and gene expression profiles revealed 12
      putative mRNA-miRNA functional pairs. Among them, miR-1207-5p and miR-575 were
      negatively correlated with p53 pathway- and cell cycle-associated genes,
      respectively. In conclusion, our study suggests that miRNAs play an important
      role in ISL-induced cytotoxicity in LCLs by targeting signaling pathways
      including p53 pathway and cell cycle.

PMID- 22995317
TI  - Recent advances in understanding the biochemical and molecular mechanism of
      diabetic cardiomyopathy.
AB  - Cardiovascular complications account for significant morbidity and mortality in
      the diabetic population. Diabetic cardiomyopathy (DCM), a prominent
      cardiovascular complication, has been recognized as a microvascular disease that
      may lead to heart failure. During the past few decades, research progress has
      been made in investigating the pathophysiology of the disease; however, the exact
      molecular mechanism has not been elucidated, making therapeutic a difficult task.
      In this review article, we have discussed a number of diabetes-induced
      metabolites such as glucose, advanced glycation end products, protein kinase C,
      free fatty acid and oxidative stress and other related factors that are
      implicated in the pathophysiology of the DCM. An understanding of the biochemical
      and molecular changes especially early in the DCM may lead to new and effective
      therapies toward prevention and amelioration of DCM, which is important for the
      millions of individuals who already have or are likely to develop the disease
      before a cure becomes available.

PMID- 22995318
TI  - Cholesterol-enriched microdomains regulate pseudopod extension in the MSP-based
      cytoskeleton of amoeboid sperm.
AB  - In the amoeboid spermatozoa from Caenorhabditis elegans, motility acquisition is
      preceded by substantial rearrangement of the plasma membrane. The current genetic
      model posits a multicomponent complex of membrane and cytoplasmic proteins
      responsible for pseudopod extension. This model can be translated into a
      physiological context through the involvement of cholesterol-enriched signaling
      platforms. We show that discrete cholesterol-enriched microdomains are present in
      C. elegans spermatids. These microdomains redistributed towards the cell body
      upon pseudopod extension resulting in a phospholipid-enriched pseudopod.
      Cholesterol saturation in the spermatids prevented pseudopod extension and
      motility acquisition, whereas cholesterol depletion increased the rate of in
      vitro pseudopod extension. This work suggests that plasma membrane cholesterol
      plays an important role in regulating the membrane dynamics that precede
      pseudopod extension and motility acquisition.

PMID- 22995319
TI  - Lipopolysaccharide induces endothelial cell apoptosis via activation of
      Na(+)/H(+) exchanger 1 and calpain-dependent degradation of Bcl-2.
AB  - The calcium-dependent protease calpain is involved in lipopolysaccharide (LPS)
      induced endothelial injury. The activation of Na(+)/H(+) exchanger (NHE) is
      responsible to increase intracellular Ca(2+) (Ca(i)(2+)) in cardiovascular
      diseases. Here we hypothesized that activation of NHE mediates LPS-induced
      endothelial cell apoptosis via calcium-dependent calpain pathway. Our results
      revealed that LPS-induced increases in NHE activity are dependent on NHE1 in
      human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with LPS
      increased the NHE1 activity in a time-dependent manner associated with the
      increased Ca(i)(2+), which resulted in enhanced calpain activity as well as
      HUVECs apoptosis via NHE1-dependent degradation of Bcl-2.

PMID- 22995320
TI  - Proteomic profiling of tumor-initiating cells in HT-29 human colorectal cancer
      cells.
AB  - Recent reports have suggested that tumors are organized in heterogeneous
      populations. Within these populations, a small subpopulation of cells is more
      capable of initiating malignancy; these are called cancer stem cells. In this
      study, HT-29 cells were sorted according to the presence or absence of the cancer
      stem cell marker CD133. We confirmed that CD133+ cells possessed higher
      clonogenicity compared to CD133- cells. Furthermore, proteomic analysis
      identified 10 proteins, including actin-related protein 2/3 complex subunit 5
      like and profilin 2. In conclusion, our data demonstrated that the expression of
      specific proteins associated with metastasis and invasion in CD133+ cells
      contributed to the stemness and tumorigenic properties of these cells.

PMID- 22995321
TI  - Extracellular matrix production and regulation in micropatterned endothelial
      cells.
AB  - Production and maintenance of extracellular matrix (ECM) is an essential aspect
      of endothelial cell (EC) function. ECM surfaces composed of collagen type IV and
      laminin support an atheroprotective endothelium, while fibronectin may encourage
      an atheroprone endothelium through inflammation or wound repair signaling. ECs
      maintain this underlying structure through regulation of protein production and
      degradation, yet the role of cytoskeletal alignment on this regulation is
      unknown. To examine the regulation and production of ECM by ECs with an
      atheroprotective phenotype, ECs were micropatterned onto lanes, which created an
      elongated EC morphology similar to that seen with unidirectional fluid shear
      stress application. Collagen IV and fibronectin protein production were measured
      as were gene expression of collagen IV, fibronectin, laminin, MMP2, MMP9, TIMP1,
      TIMP2, and TGF-beta1. ECs were also treated with TNF to simulate an injury model.
      Micropattern-induced elongation led to significant increases in collagen IV and
      fibronectin protein production, and collagen IV, laminin, and TGF-beta1 gene
      expression, but no significant changes in the MMP or TIMP genes. TNF treatment
      significantly increased collagen IV gene and protein production. These results
      suggest that the increase in ECM synthesis in micropattern-elongated ECs is
      likely regulated with TGF-beta1, and this increase in ECM could be relevant to
      the atheroprotection needed for maintenance of a healthy endothelium in vivo.

PMID- 22995322
TI  - Anxiolytic-like activity and GC-MS analysis of (R)-(+)-limonene fragrance, a
      natural compound found in foods and plants.
AB  - The traditional use of essential oils in aromatherapy has offered numerous health
      benefits. However, few scientific studies have been conducted with these oils to
      confirm their therapeutic efficacy. (+)-Limonene is a chemical constituent of
      various bioactive essential oils. The present study reports on the anxiolytic
      like effects of (+)-limonene in an elevated maze model of anxiety in mice. At
      concentrations of 0.5% and 1.0%, (+)-limonene, administered to mice by
      inhalation, significantly modified all the parameters evaluated in the elevated
      plus maze test. The pharmacological effect of inhaled (+)-limonene (1%) was not
      blocked by flumazenil. Analysis of (+)-limonene using gas chromatography-mass
      spectrometry (GC-MS) showed its volatility to be high. These data suggest
      possible connections between the volatility of (+)-limonene and its anxiolytic
      like effect on the parameters evaluated in the elevated plus maze test. The data
      indicate that (+)-limonene could be used in aromatherapy as an antianxiety agent.

PMID- 22995323
TI  - Safety and early treatment effects of the CXCR2 antagonist SB-656933 in patients
      with cystic fibrosis.
AB  - BACKGROUND: It is hypothesized that a CXCR2 receptor antagonist would inhibit the
      recruitment and activation of neutrophils and other inflammatory cells into the
      lung in subjects with cystic fibrosis. The objective of this study was to
      evaluate the safety, tolerability and pharmacodynamics of SB-656933, an oral
      CXCR2 antagonist. METHODS: 146 adult CF patients were randomized to receive
      either placebo or SB-656933 20mg or 50mg once daily for 28days. The primary
      endpoint was safety; secondary endpoints included pharmacokinetics, blood and
      sputum biomarkers, sputum microbiology, pulmonary function and respiratory
      symptoms. RESULTS: SB-656933 was generally well tolerated. The most frequent
      adverse event was headache. Five subjects were withdrawn due to adverse events.
      In subjects receiving SB-656933 50mg, sputum neutrophils and elastase were
      reduced compared to baseline (probability of a true reduction, 0.889 and 0.882
      respectively), and free DNA reduced compared to placebo (probability of a true
      reduction, 0.967), while blood levels of fibrinogen, CRP and CXCL8 were
      increased. There were no changes in lung function or respiratory symptoms.
      Average plasma concentrations of SB-656933 were lower than predicted based on
      previous studies, only breaching IC50 for ~4h at the 50mg dose. CONCLUSIONS: SB
      656933 was well-tolerated in adult patients with cystic fibrosis. Patients
      receiving a daily dose of 50mg showed trends for improvement in sputum
      inflammatory biomarkers despite potential blunting of effects by lower than
      expected plasma concentrations. Although the increase in systemic inflammatory
      markers requires further evaluation, CXCR2 antagonism may be a useful approach
      for modulating airway inflammation in patients with cystic fibrosis. Clinical
      trial registered with www.clinicaltrials.gov (NCT00903201).

PMID- 22995324
TI  - [Bone metastases in muscle invasive bladder carcinoma: clinical consideration].

PMID- 22995325
TI  - [Use of a polymeric gel to prevent retropulsion during intracorporeal
      lithotripsy].
AB  - INTRODUCTION: Stone retropulsion during ureteroscopic lithotripsy may lead to
      additional procedures needed for residual calculi. Several devices have been
      introduced in an attempt to reduce retropulsion. We set out to report our initial
      experience utilizing the new polymeric gel, BackStop. MATERIAL AND METHODS: We
      prospectively collected data on 7 ureteroscopy procedures with distal ureteral
      calculi treated with BackStop. Perioperative data including stone size, location,
      operative time, stone free rate, the presence or absence of retropulsion was
      collected. Success was defined as no residual fragments, no retropulsion, and no
      additional procedures required. RESULTS: All of the patients were rendered stone
      free after URS and no retropulsion occurred. There were no intraoperative
      complications nor gel migration or problems with dissolving the gel. CONCLUSIONS:
      BackStop is a new promising therapy to prevent retropulsion during ureteral
      intracorporeal lithotripsy. It is safe, easy to apply and very effective in
      preventing stone fragment migration. BackStop has the potential to reduce
      operative time.

PMID- 22995326
TI  - [Randomized comparative study for the assessment of a new therapeutic schedule of
      fosfomycin trometamol in postmenopausal women with uncomplicated lower urinary
      tract infection].
AB  - OBJECTIVES: To compare two therapeutic regimes in terms of bacterial eradication
      of post-menopausal with uncomplicated acute cystitis who complete antibiotic
      treatment. MATERIALS AND METHOD: A multicenter, randomized, prospective and
      controlled study between two short antibiotic regimes: fosfomycin trometamol
      (FMT) 3g, 2 doses separated by 72hours and ciprofloxacin 250mg every 12hours for
      3 days. A total of 118 post-menopausal women were enrolled in the study. They
      underwent an initial urine culture to know the responsible microorganism and
      susceptibility to treatment. This was repeated 5-7 days and 4 weeks after the
      treatment to evaluate bacterial eradication. Clinical symptoms and treatment
      safety were also evaluated. RESULTS: There were microbiological data at the onset
      of the treatment in 82 women (69.49%). Of these, 27 did not have positive culture
      at the first visit (30.51%), 76 (64.41%) fulfilled all the protocol requirements
      and adverse effects from the treatment were collected in 113 (95.76%) of the
      patients enrolled in the study. The germs isolated most frequently were
      Escherichia coli (E. coli) (76.83%), Klebsiella pneumoniae (K. pneumoniae)
      (7.32%), Proteus mirabilis (P. mirabilis) (4.89%) and Enterococo sp. (3.66%). In
      terms of efficacy, no differences were detected in the proportion of patients who
      achieved bacterial eradication between the two study arms: 62.16% of the patients
      who received FMT and 58.97% of those treated with ciprofloxacin (chi-square,
      p=0.78). The proportion of patients who achieved clinical cure was also similar
      (86.49% for FMT and 82.05% for ciprofloxacin; square, p=0.59). These results
      indicate similar efficacy of both antibiotics in the treatment of uncomplicated
      lower tract urinary infection in post-menopausal women. In regards to safety
      data, the proportion of global adverse effects associated to the treatments was
      3.45% for FMT and 9.09% for ciprofloxacin. Treatment compliance was 100% for FMT
      and 83.64% for ciprofloxacin. CONCLUSIONS: The FMT administered at a dose of 3g
      every 72hours (2 total doses) and ciprofloxacin at a dose of 250mg every 12hours
      during 3 days (6 total doses) have a comparable efficacy profile in lower tract
      urinary infection in post-menopausal women who adequately comply with the
      treatment, also having comparable safety. The FMT has a better antimicrobial
      susceptibility profile and better rate of treatment compliance.

PMID- 22995327
TI  - Differential expression of extracellular matrix-related genes in rare variants of
      meningioma.
AB  - Secretory, clear cell, and rhabdoid meningiomas are rare variants of meningiomas
      characterized by unique histologies and behaviors. Extracellular matrix proteins
      provide a morphologic structure and influence the biologic behavior of tumors.
      However, the effects of extracellular matrix proteins on morphologies and
      biologic behaviors of secretory meningioma, clear cell meningioma, and rhabdoid
      meningioma have not been established. We evaluated the expression of matrix
      metalloproteinase 2, matrix metalloproteinase 9, galectin-3, fibronectin, and
      collagen IV in a series of those rare variants of meningioma and verified their
      clinicopathologic significance. A total 51 cases included 12 secretory
      meningiomas, 9 clear cell meningiomas, and 30 rhabdoid meningiomas. Extracellular
      matrix proteins showed different expression patterns according to the histologic
      subtypes, and messenger RNA levels were well correlated with immunoexpressions.
      Secretory meningiomas showed high expressions of fibronectin and galectin-3.
      Clear cell meningiomas showed high expression of matrix metalloproteinase 2,
      matrix metalloproteinase 9, and collagen IV. Rhabdoid meningiomas showed high
      expressions of matrix metalloproteinase 9, galectin-3, and fibronectin.
      Clinically, high expression of matrix metalloproteinase 9 was associated with
      tumor recurrence (P < .001) and local invasion at the time of diagnosis (P =
      .018) among the extracellular matrix-related proteins, and was also associated
      with shorter recurrence-free survival (P = .025) in the patients with rhabdoid
      meningioma. In conclusion, the differential expressions of extracellular matrix
      related genes according to the histologic subtypes appear to be involved in
      biologic behavior and clinical outcome, and high matrix metalloproteinase 9
      expression is associated with recurrences in rhabdoid meningiomas.

PMID- 22995328
TI  - An imbalance between substance P and vasoactive intestinal polypeptide might
      contribute to the immunopathology of megaesophagus after Trypanosoma cruzi
      infection.
AB  - Megaesophagus is one of the major causes of morbidity in chronic Chagas disease,
      and extensive denervation, associated with an inflammatory process, is recognized
      as the key factor for alterations in motility and disease development. Here, we
      analyzed esophagus samples from necropsied, infected individuals--6 cases with
      megaesophagus and 6 cases without megaesophagus--for the relative areas of
      expression of 2 neuromediators, substance P and vasoactive intestinal peptide,
      which are known to activate or inhibit, respectively, local immune cells. Samples
      from 6 noninfected individuals were used as controls. Esophageal sections were
      immunohistochemically stained for protein gene product 9.5, vasoactive intestinal
      peptide, and substance P, and the relative areas of expression of the latter 2
      were calculated. Morphometric analyses revealed increased substance P and
      decreased vasoactive intestinal peptide relative areas in esophageal sections
      from patients with megaesophagus. Furthermore, in the group of patients without
      megaesophagus, the loss of vasoactive intestinal peptide positively correlated
      with the denervation process. We suggest that an imbalance between vasoactive
      intestinal peptide and substance P production results in the reestablishment and
      maintenance of the inflammatory process, leading to denervation and,
      consequently, promoting the development of megaesophagus.

PMID- 22995329
TI  - The pluripotent renal stem cell regulator SIX2 is activated in renal neoplasms
      and influences cellular proliferation and migration.
AB  - Embryonal renal mesenchyme contains pluripotent progenitor cells characterized by
      expression of SIX2, which suppresses cellular differentiation. Additionally
      hypomethylation of the promotor region in renal neoplasms indicates a role of
      SIX2 in tumorigenesis. This study focuses therefore on the investigation of SIX2
      in different renal neoplasms and the mode and consequences of SIX2 activation.
      Expression of SIX2 was determined in renal cell carcinomas, nephroblastomas, and
      dysplastic kidneys using immunohistochemistry and quantitative real-time
      polymerase chain reaction. Its potential mode of activation was assessed by
      measuring upstream activators by quantitative real-time polymerase chain reaction
      and the level of methylation of the promoter region by quantitative DNA
      methylation analysis. Consequences of SIX2 activation were investigated by
      overexpressing SIX2 in a cell line. Forty-seven of 49 renal clear cell carcinomas
      showed nuclear staining of SIX2, whereas all papillary carcinomas were negative.
      In nephroblastomas of various subtypes blastema showed a significant up
      regulation (P < .01) and a strong nuclear protein expression of SIX2 in contrast
      to negative epithelial and mesenchymal areas. 11 cases of dysplastic kidneys were
      entirely negative. Upstream activators of SIX2 indicated an activation of the
      signal transduction pathway in most samples. No difference of promoter
      methylation status was observed between blastema and epithelial structures. A
      significantly higher percentage of cells in the S-phase and an increased
      migration were detected in the cell-line overexpressing SIX2. Our study suggests
      that activation of SIX2 might contribute to the pathogenesis of renal clear cell
      carcinomas and nephroblastomas. SIX2 also appears to be a valuable marker for
      minimal residual blastema contributing to the prognosis of nephroblastomas.

PMID- 22995330
TI  - Bone marrow morphology predicts additional chromosomal abnormalities in patients
      with myelodysplastic syndrome with del(5q).
AB  - The current World Health Organization classification considers myelodysplastic
      syndrome with isolated del(5q) a distinct entity owing to its characteristic
      clinical and pathologic features. Recently, several studies have examined
      survival, leukemic transformation, and various prognostic factors in these
      patients. However, there is a lack of detailed comparative pathologic analysis of
      myelodysplastic syndrome cases in which del(5q) is present in association with
      additional cytogenetic abnormalities. We studied 26 cases of myelodysplastic
      syndrome at initial diagnosis with 5q- alone, 5q- plus 1 additional abnormality,
      and 5q- as part of a complex karyotype. Four of 17 patients had evidence of JAK2
      V617F mutation. In contrast to cases of myelodysplastic syndrome with isolated 5q
      , patients with additional abnormalities had normal mean corpuscular volume and
      decreased platelet counts (P < .001). Based on bone marrow examination, they were
      significantly more likely to have increased cellularity, trilineage dysplasia,
      lower proportion of small hypolobated megakaryocytes, higher number of blasts,
      and fibrosis. The presence of these morphologic features can be used to
      distinguish these more aggressive cases from those with myelodysplastic syndrome
      with isolated 5q- and a more benign clinical course.

PMID- 22995331
TI  - Massive localized lymphedema of the male external genitalia: a clinicopathologic
      study of 6 cases.
AB  - Massive localized lymphedema is a reactive pseudotumor strongly associated with
      obesity. The tumor most commonly presents as pendulous masses in the lower limbs
      with only 3 reported cases involving external male genitalia. In this study, we
      report an additional 6 cases localized to the external male genitalia. The cases
      were retrospectively identified from the surgical pathology database of the Johns
      Hopkins Hospital. All 6 patients were obese (5 presented with diffuse scrotal
      edema and 1 with a penile mass). In all cases, the clinical impression was of a
      benign chronic process developing over 3 months to 1 year. All 3 cases from
      outside institutions were referred with benign pathologic diagnoses. The lesions
      ranged in size from 4 to 55 cm. Microscopically, all cases exhibited stromal
      fibrosis and edema, multinucleated stromal cells, perivascular chronic
      inflammation, and lymphangiectasia. Entrapped fat was a minor feature and seen in
      only 3 cases. Variable hyperplasia and hypertrophy of dartos muscle were noted in
      6 lesions. Three cases showed prominent microvascular proliferation around the
      edge of individual dartos muscle bundles. In summary, diagnosis of massive
      localized lymphedema requires appropriate correlation between clinical and
      microscopic findings. Lesions in the male external genitalia share many
      microscopic findings with massive localized lymphedema at other sites, although
      entrapped adipose tissue is not prominent. Additional, although not specific,
      findings include variably hyperplastic and hypertrophic dartos muscle and
      capillary neoangiogenesis at the interface between smooth muscle bundles and
      stroma.

PMID- 22995332
TI  - Early mitotic inhibitor-1, an anaphase-promoting complex/cyclosome inhibitor, can
      control tumor cell proliferation in hepatocellular carcinoma: correlation with
      Skp2 stability and degradation of p27(Kip1).
AB  - Early mitotic inhibitor-1 (Emi1) is a key cell-cycle regulator that promotes S
      phase and M-phase entry by inhibiting anaphase-promoting complex/cyclosome
      (APC/C) activity. Immunohistochemical analysis was performed in 114 human
      hepatocellular carcinoma (HCC) samples, and the data were correlated with
      clinicopathologic features. Univariate and multivariate survival analyses were
      performed to determine the prognostic significance of the proteins. Expression of
      Emi1 correlated directly with the stage of HCC. More importantly, high expression
      of Emi1 was associated with a poor outcome. Western blot analysis showed that
      Emi1 was highly expressed in HCC compared with the adjacent noncancerous tissue.
      In vitro, after the release of HCC cell lines from serum starvation, the
      expression of Emi1 APC/C substrates (cyclins A, B) and Skp2 was up-regulated,
      whereas p27(Kip1) was down-regulated. In addition, we used small interfering RNA
      to knock out Emi1 expression and observed its effects on HCC growth in vitro to
      determine whether loss of Emi1 could inhibit cell proliferation by blocking S
      phase and mitotic entry. Western blot analyses indicated that deletion of Emi1
      was positively correlated with APC/C substrates (cyclins A, B) and Skp2 but was
      negatively correlated with p27(Kip1). Emi1 inhibits APC/C activity, whereas Skp2
      degradation is mediated by APC/C, and degradation of Skp2 can stabilize
      p27(kip1). These results suggested that Emi1 participates in HCC cell
      proliferation and that progression is controlled by APC/C inhibition, which
      stabilized Skp2 and enabled p27(kip1) degradation. These findings provide a
      potential therapeutic strategy for HCC.

PMID- 22995333
TI  - Immunohistochemical profile to distinguish urothelial from squamous
      differentiation in carcinomas of urothelial tract.
AB  - Urothelial neoplasms with squamous morphology raise the differential diagnosis
      between pure primary squamous cell carcinoma, urothelial carcinoma with squamous
      differentiation and secondary involvement by squamous cell carcinoma, for
      example, from uterine cervix. Accurate identification between these entities is
      critical due to differing prognosis and therapeutic strategies. We evaluated the
      utility of an immunohistochemical panel of 3 urothelial-associated antibodies
      (uroplakin III, S100P, and GATA3) and two squamous-associated antibodies (CK14
      and desmoglein-3) in 50 primary urothelial neoplasms: 15 pure urothelial
      carcinomas, 12 pure squamous cell carcinomas and 23 urothelial carcinomas with
      squamous differentiation. Squamous differentiation was defined by intercellular
      bridges or evidence of keratinization. Pure squamous cell carcinomas were
      positive for CK14 (100%) and desmoglein-3 (75%), negative for GATA3 and uroplakin
      III; one case was S100P positive (9%). Pure urothelial carcinomas had an opposite
      pattern and were positive for S100P (93%), GATA3 (93%), and uroplakin III (67%)
      and were negative for desmoglein-3; CK 14 was positive in 27% of cases; 74% of
      urothelial carcinomas with squamous differentiation had expression of urothelial
      and squamous associated markers (S100P, 83%; GATA3, 35%; uroplakin III, 13%;
      CK14, 87%; and desmoglein-3, 70%), although reactivity for individual markers
      within some tumors did not always correspond with morphologic differentiation. Of
      the remaining 26%, 4 showed an overall "squamous" immunoprofile, whereas 2 cases
      showed a "urothelial" immunoprofile. Our study showed that a panel of five
      antibodies identifies squamous and urothelial differentiation in most instances
      suggesting potential diagnostic utility.

PMID- 22995335
TI  - Standardized activities of daily living in presence of sub-acute low-back pain: a
      pilot study.
AB  - The aim of this pilot study was to investigate how sub-acute low-back pain (LBP)
      patients differed with respect to control in movements and muscle activation
      during standardized tasks representing daily living activities, and explore
      relationships between cognition and measured motor performance. Linear and
      nonlinear parameters were computed from kinetics, kinematics and muscle activity
      recorded for 12 sub-acute patients and 12 healthy matched controls during trunk
      flexion, sit-to-stand from a chair and lifting a box. Cognitive variables were
      collected to explore relationships with biomechanical parameters. For trunk
      flexion, left external abdominal oblique muscle activity level was lower for
      patients compared with controls (p < 0.05), whereas sample entropy (complexity)
      was higher (p < 0.05). Normalized mutual information was lower for patients
      compared with controls for left and right erector spinae (p < 0.05). Level of
      activity of left external abdominal oblique correlated negatively with cognitive
      ignoring and positively with catastrophizing (p <= 0.05), and catastrophizing
      also correlated positively with functional connectivity of abdominal muscles (p <
      0.05). Signs of reorganization in muscle activation pointed towards different
      synergistic actions in trunk muscles in sub-acute LBP patients compared with
      controls. The interplay with maladaptive cognition suggested that in the subacute
      stage of LBP, both biomechanical and cognitive factors should be taken into
      account.

PMID- 22995334
TI  - Expression of the vitamin D-activating enzyme 1alpha-hydroxylase (CYP27B1)
      decreases during melanoma progression.
AB  - 1alpha-Hydroxylase (CYP27B1), the enzyme responsible for the synthesis of the
      biologically active form of vitamin D (1,25(OH)(2)D(3)), is expressed in the
      skin. To assess the correlation between progression of melanocytic tumors and
      CYP27B1, we analyzed its expression in 29 benign nevi, 75 primary cutaneous
      melanomas, 40 metastases, and 4 re-excision and 6 normal skin biopsies.
      Immunoreactivity for CYP27B1 was significantly lower in the vertical growth phase
      and metastatic melanomas (0.6 and 0.5 arbitrary units, respectively) in
      comparison with nevi and radial growth phase tumors (1.2 and 1.1 arbitrary units,
      respectively); and expression was reduced in more advanced lesions (Clark levels
      III-V, Breslow thickness >=2.1 mm; 0.8 and 0.7 arbitrary units, respectively).
      There was an inverse correlation between CYP27B1 and Ki-67 expression.
      Furthermore, CYP27B1 expression was reduced in primary melanomas that created
      metastases in comparison with non-metastasizing melanomas. Reduced CYP27B1
      expression in radial growth phase was related to shorter overall survival (810
      versus 982 versus 1151 days in melanomas with absent, low, and high CYP27B1
      immunoreactivity), and low CYP27B1 expression in radial growth phase and vertical
      growth phase was related to shorter disease-free survival (114 versus 339 versus
      737 days and 129 versus 307 versus 737 days, respectively, in melanomas with
      absent, low, and high CYP27B1). Also, CYP27B1 expression was inversely related to
      melanin in melanoma cells in vivo and melanoma cells cultured in vitro. Thus,
      reduction of CYP27B1 correlates with melanoma phenotype and behavior, and its
      lack affects the survival of melanoma patients, indicating a role in the
      pathogenesis and progression of this cancer.

PMID- 22995337
TI  - "When he's around his brothers ... he's not so quiet": the private and public
      worlds of school-aged children with speech sound disorder.
AB  - Children interact with people in context: including home, school, and in the
      community. Understanding children's relationships within context is important for
      supporting children's development. Using child-friendly methodologies, the
      purpose of this research was to understand the lives of children with speech
      sound disorder (SSD) in context. Thirty-four interviews were undertaken with six
      school-aged children identified with SSD, and their siblings, friends, parents,
      grandparents, and teachers. Interview transcripts, questionnaires, and children's
      drawings were analyzed to reveal that these children experienced the world in
      context dependent ways (private vs. public worlds). Family and close friends
      typically provided a safe, supportive environment where children could be
      themselves and participate in typical childhoods. In contrast, when out of these
      familiar contexts, the children often were frustrated, embarrassed, and
      withdrawn, their relationships changed, and they were unable to get their message
      across in public contexts. Speech-language pathology assessment and intervention
      could be enhanced by interweaving the valuable insights of children, siblings,
      friends, parents, teachers, and other adults within children's worlds to more
      effectively support these children in context. LEARNING OUTCOMES: 1. Recognize
      that children with SSD experience the world in different ways, depending on
      whether they are in private or public contexts. 2. Describe the changes in the
      roles of family and friends when children with SSD are in public contexts. 3.
      Discover the position of the child as central in Bronfenbrenner's bioecological
      model. 4. Identify principles of child-friendly research. 5. Recognize the
      importance of considering the child in context during speech-language pathology
      assessment and intervention.

PMID- 22995336
TI  - Differences of articulation rate and utterance length in fluent and disfluent
      utterances of preschool children who stutter.
AB  - PURPOSE: The purpose of this study was to investigate characteristics of four
      types of utterances in preschool children who stutter: perceptually fluent,
      containing normal disfluencies (OD utterance), containing stuttering-like
      disfluencies (SLD utterance), and containing both normal and stuttering-like
      disfluencies (SLD+OD utterance). Articulation rate and length of utterance were
      measured to seek the differences. Because articulation rate may reflect temporal
      aspects of speech motor control, it was predicted that the articulation rate
      would be different between perceptually fluent utterances and utterances
      containing disfluencies. The length of utterance was also expected to show
      different patterns. METHOD: Participants were 14 preschool children who stutter.
      Disfluencies were identified from their spontaneous speech samples, and
      articulation rate in syllables per second and utterance length in syllables were
      measured for the four types of utterances. RESULTS AND DISCUSSION: There was no
      significant difference in articulation rate between each type of utterance.
      Significantly longer utterances were found only in SLD+OD utterances compared to
      fluent utterances, suggesting that utterance length may be related to efforts in
      executing motor as well as linguistic planning. The SLD utterance revealed a
      significant negative correlation in that longer utterances tended to be slower in
      articulation rates. Longer utterances may place more demand on speech motor
      control due to more linguistic and/or grammatical features, resulting in
      stuttering-like disfluencies and a decreased rate.

PMID- 22995338
TI  - Zoonotic Cryptosporidium parvum in Romanian newborn lambs (Ovis aries).
AB  - This study was undertaken to investigate the occurrence and public health
      significance of Cryptosporidium species/genotypes and subtypes in a newborn
      lambs. A total of 175 diarrheic fecal samples from lambs (younger than 21 days)
      were collected in seven sheep flocks located in western Romania, and were
      microscopically examined for the presence of Cryptosporidium oocysts after
      staining with modified Ziehl-Neelsen technique. Twenty-four (13.7%) fecal samples
      were tested Cryptosporidium positive by microscopy and were subjected for
      molecular characterization. All positive samples were successfully amplified
      through a nested polymerase chain reaction (PCR) of the small subunit (SSU) rRNA
      gene (18S). Cryptosporidium species were determined by restriction fragment
      length polymorphism (RFLP) analysis of the secondary PCR products using the
      conventional SspI and VspI restriction enzymes. The identified species were:
      Cryptosporidium parvum (20/24), C. ubiquitum (2/24) and C. xiaoi (2/24),
      respectively. PCR-RFLP results for C. ubiquitum and C. xiaoi isolates were
      confirmed by DNA sequencing. Subsequently, subtyping of seven randomly selected
      C. parvum isolates, based on sequence analysis of the GP60 gene, revealed the
      presence of five different subtypes (IIaA17G1R1, IIaA16G1R1, IIdA20G1, IIdA24G1
      and IIdA22G2R1) belonging in two zoonotic subtype families (IIa and IId). These
      findings may suggest the potential role of the newborn lambs as a source for
      human cryptosporidiosis. This is the first published report about the presence of
      C. ubiquitum and C. xiaoi in lambs from Romania.

PMID- 22995339
TI  - A breach in the scaffold: the possible role of cytoskeleton dysfunction in the
      pathogenesis of major depression.
AB  - Depression is one of the most common psychiatric disorders with inadequately
      understood disease mechanisms. It has long been considered that dendritic
      regression and decrease in the number of dendritic spines are involved in
      depression. Dendrites made up of microtubules and actin filaments form synapses
      with neighboring neurons, which come together as an important communication
      network. Cytoskeletal proteins undergo post-translational modifications to define
      their structure and function. In depression and other psychiatric disorders, post
      translational modifications may be disrupted that can result in altered
      cytoskeletal functions. The disruption of microtubule and actin in terms of
      morphology and functions may be a leading cause of dendritic regression and
      decrease in dendritic spine in depression.

PMID- 22995340
TI  - Functional, balance and health determinants of falls in a free living community
      Amazon riparian elderly.
AB  - The aim of this study was to investigate socio-economic, clinical,
      anthropometric, balance and functional fitness factors present in Amazon riparian
      older persons that can be associated with a risk of falling. A cross sectional
      study was performed with 637 riverine elderly residents (>=60 years old) in Maues
      city Amazonas, Brazil. The elderly were grouped in two categories with and
      without a history of falls in the past six months. The following variables were
      compared between these groups: self-reported social and health conditions;
      biochemical and physiological variables related to the control of metabolic
      diseases; body composition; hand grip strength; functional fitness evaluation
      using the Senior Fitness Test (SFT) battery, and balance condition using the Berg
      Balance Test (BBT). The prevalence of at least one fall in the past six months
      was 24.6% (n=157) and was similar between the sexes. The mean age between males
      and females with and without a history of falls was also similar (males with
      falls=72.67 +/- 8.86; males with no falls=73.26 +/- 7.58) female falls=71.78 +/-
      8.18, female with no falls=71.48 +/- 8.17). A history of falls was associated
      with hospitalization in the last year and to self-health perception to both sexes
      and presence of chronic morbidity and percentage of body fat (BF) to women.
      However, the other variables including balance and functional fitness, did not
      present differences between elderly with and without a history of falls. These
      results suggest that falls experienced by the riparian elderly are strongly
      associated to accidents due to environmental conditions related to daily life.

PMID- 22995341
TI  - Relationship between going outdoors daily and activation of the prefrontal cortex
      during verbal fluency tasks (VFTs) among older adults: a near-infrared
      spectroscopy study.
AB  - This study sought to investigate the relationship between going outdoor daily and
      prefrontal cortex activation during execution of the VFT using near-infrared
      spectroscopy (NIRS) in community-dwelling older adults. Blood oxygenation changes
      in left and right prefrontal cortices were measured in twenty older adults (mean
      age 76.1 +/- 6.7 years) by NIRS during VFT performance. In this task,
      participants were required to pronounce as many nouns as possible beginning with
      the letters "Shi," "I," and "Re." Changes in oxygenated hemoglobin (oxy-Hb)
      levels during the VFT were compared between two groups defined by the frequency
      of going outdoors: daily or non-daily within a week. Participants in both groups
      exhibited significantly increased oxy-Hb levels in the left and right prefrontal
      cortices during the VFT compared to a resting baseline condition. After
      controlling for age and gender, there were significant group-by-condition
      interactions on oxy-Hb levels with less activation during the execution of the
      VFT over both cortices in the non-daily group (left: F=4.76, p=0.04; right:
      F=6.32, p=0.02). These findings indicate that going outdoors daily is associated
      with increased activation in the prefrontal cortices during VFT performance in
      community-dwelling older adults.

PMID- 22995342
TI  - Smoking in elderly Koreans: prevalence and factors associated with smoking
      cessation.
AB  - The aims of this study were to investigate the prevalence of smoking and to
      explore the factors associated with smoking cessation. 1118 Koreans were randomly
      sampled from the residents aged 65 years or older living in Seongnam, Korea.
      Structured face-to-face interviews with neurological and physical examinations
      were conducted to the 714 respondents. A current smoker was defined as a person
      who had been smoking at least one cigarette per day for 1 year, and a past smoker
      as a person who used to smoke but had not smoked in the past 1 year. Nicotine
      dependence was defined as having the Fagerstrom Test for Nicotine Dependence
      (FTND) score of 4 or higher. Age- and gender-standardized prevalence of ever
      smoker, past smoker and current smoker among the elderly Koreans aged 65 and over
      were estimated to be 36.3% (95% CI=32.7-39.8), 24.4% (95% CI=21.2-27.5) and 11.9%
      (95% CI=9.5-14.3), respectively. Current smokers were much more prevalent in men
      (23.3%) than in women (3.9%), but did not decline with advancing age in both
      genders. 36.0% (21 men, 10 women) of the current smokers were nicotine-dependent.
      The smokers with depression or alcohol use disorder (AUD) were less likely and
      those who were educated more or inhaled smoke more deeply were more likely to
      quit smoking. Thus, smoking is common in the elderly men, and treatments of
      depression and AUD may be helpful in increasing smoking cessation rate among
      elderly Koreans.

PMID- 22995344
TI  - Identification and sequence analysis of the keratin-associated protein 24-1
      (KAP24-1) gene homologue in sheep.
AB  - Keratin-associated proteins (KAPs) are major structural components of hair and
      wool fibres, and play a critical role in determining the properties of the fibre.
      While over 100 KAP genes that have been grouped into 27 KAP families have been
      identified in mammals, most homologues remain unidentified in sheep. A BLAST
      search of the Ovine Genome Assembly v2.0 using a human KRTAP24-1 coding sequence
      (NM_001085455), identified a putative ovine KAP24-1 gene clustered with six other
      known KAP genes on chromosome 1. The KAP24-1 gene was amplified from the genomic
      DNA of 260 New Zealand Romney-cross sheep and stem-loop conformational
      polymorphism (SLCP) analysis of the amplicons revealed four unique banding
      patterns, representing four different DNA sequences. These sequences were not
      closely homologous with any known ovine KRTAP and the highest similarity was with
      KRTAP24-1 sequences from humans, cattle, dog, pig, Sumatran orangutan and
      northern white-cheeked gibbon. This suggests that the sequences were allelic
      variants of ovine KRTAP24-1. Among these four sequences, seven nucleotide
      substitutions in the coding region were identified and four of the substitutions
      were non-synonymous. The putative ovine KAP24-1 polypeptide consisted of 252
      amino acids. While probably belonging to the high-sulphur KAP group, the
      polypeptide had a moderate level of cysteine, but a high content of serine and
      tyrosine. The polypeptide possesses two putative N-glycosylation sites and a
      number of residues that may be O-glycosylated and/or phosphorylated.

PMID- 22995343
TI  - Outfits for different occasions: tissue-specific roles of Nuclear Envelope
      proteins.
AB  - The Nuclear Envelope (NE) contains over 100 different proteins that associate
      with nuclear components such as chromatin, the lamina and the transcription
      machinery. Mutations in genes encoding NE proteins have been shown to result in
      tissue-specific defects and disease, suggesting cell-type specific differences in
      NE composition and function. Consistent with these observations, recent studies
      have revealed unexpected functions for numerous NE associated proteins during
      cell differentiation and development. Here we review the latest insights into the
      roles played by the NE in cell differentiation, development, disease and aging,
      focusing primarily on inner nuclear membrane (INM) proteins and nuclear pore
      components.

PMID- 22995345
TI  - Transcription of the AML1/ETO chimera is guided by the P2 promoter of the AML1
      gene in the Kasumi-1 cell line.
AB  - Chromosomal translocation t (8;21)(q22;22) is one of the most frequent
      cytogenetic abnormalities found in acute myeloid leukaemia (AML). It generates
      the AML1/ETO fusion gene, which itself supports human haematopoietic stem cell
      self-renewal. However, the mechanism guiding transcription of this chimeric gene
      remains unclear. In our work, we attempted to shed light on this essential issue.
      We investigated the promoter from which transcription of the AML1/ETO gene is
      initiated and defined the three-dimensional structure of the whole rearranged
      locus.

PMID- 22995346
TI  - De novo sequencing and comparative analysis of the blueberry transcriptome to
      discover putative genes related to antioxidants.
AB  - Blueberry (Vaccinium spp.) is an important small fruit crop rich in antioxidants.
      However, tissue-specific transcriptome and genomic data in public databases are
      not sufficient for an understanding of the molecular mechanisms associated with
      antioxidants, especially the biosynthesis of anthocyanins. Here, we obtained more
      than 64 million sequencing reads from blueberry skin and pulp using Illumina
      sequencing technology. De novo assemblies yielded 34,464 unigenes, among them
      1236 transcripts and 862 putative transcription factors involved in the main
      antioxidant biosynthesis pathway were identified. Comparative transcript
      profiling allowed the identification of 92 differentially expressed genes with
      potential relevance in regulating the fruit metabolism and anthocyanin content
      during ripening. A series of qRT-PCR confirmed the high expression level of the
      anthocyanin pathway genes in the skin of the blue fruit from the in silico study.
      This sequence collection provides a significant resource for the blueberry
      research and breeding work.

PMID- 22995347
TI  - Monosomy 9pter and trisomy 9q34.11qter in two sisters due to a maternal
      pericentric inversion.
AB  - Pericentric inversions of chromosome 9 leading to unbalanced live-born offspring
      are relatively rare and so far only four cases have been reported. Here we
      present two sisters with an unbalanced recombinant chromosome 9 which resulted
      from a large maternal pericentric inversion inv(9)(p24.3q34.1). Further molecular
      characterisation of the aberrant chromosome 9 by 250k SNP array analysis showed a
      terminal 460 kb loss of 9p24.3 and a terminal 8.9 Mb gain of 9q34.11. We compared
      the clinical features of these two patients with the previous reported four cases
      as well as with patients with similar sized 9pter deletions or 9qter
      duplications. Based upon this study, we suggest that the recombinant chromosome 9
      phenotype is mainly the result of duplication of a 3.4 Mb region of chromosome
      9q34.11q34.13.

PMID- 22995348
TI  - Genomic diversity and affinities in population groups of North West India: an
      analysis of Alu insertion and a single nucleotide polymorphism.
AB  - The North West region of India is extremely important to understand the peopling
      of India, as it acted as a corridor to the foreign invaders from Eurasia and
      Central Asia. A series of these invasions along with multiple migrations led to
      intermixture of variable populations, strongly contributing to genetic
      variations. The present investigation was designed to explore the genetic
      diversities and affinities among the five major ethnic groups from North West
      India; Brahmin, Jat Sikh, Bania, Rajput and Gujjar. A total of 327 individuals of
      the abovementioned ethnic groups were analyzed for 4 Alu insertion marker loci
      (ACE, PV92, APO and D1) and a Single Nucleotide Polymorphism (SNP) rs2234693 in
      the intronic region of the ESR1 gene. Statistical analysis was performed to
      interpret the genetic structure and diversity of the population groups. Genotypes
      for ACE, APO, ESR1 and PV92 loci were found to be in Hardy-Weinberg equilibrium
      in all the ethnic groups, while significant departures were observed at the D1
      locus in every investigated population after Bonferroni's correction. The average
      heterozygosity for all the loci in these ethnic groups was fairly substantial
      ranging from 0.3927 +/- 0.1877 to 0.4333 +/- 0.1416. Inbreeding coefficient
      indicated an overall 10% decrease in heterozygosity in these North West Indian
      populations. The gene differentiation among the populations was observed to be of
      the order of 0.013. Genetic distance estimates revealed that Gujjars were close
      to Banias and Jat Sikhs were close to Rajputs. Overall the study favored the
      recent division of the populations of North West India into largely endogamous
      groups. It was observed that the populations of North West India represent a more
      or less homogenous genetic entity, owing to their common ancestral history as
      well as geographical proximity.

PMID- 22995353
TI  - Dementia: a global health priority - highlights from an ADI and World Health
      Organization report.
AB  - Alzheimer's Disease International is the worldwide federation of Alzheimer
      associations that represent people with dementia and their families. Alzheimer's
      Disease International has commissioned a number of World Alzheimer Reports since
      2009 and was involved in the recently launched report Dementia: A Public Health
      Priority by the World Health Organization. From these reports, we can learn about
      the growing impact of Alzheimer's disease and other dementias on our societies
      and the need to take action. Developing national Alzheimer plans is a key tool
      for this action. 

PMID- 22995349
TI  - Aberrant transcript produced by a splice donor site deletion in the TECTA gene is
      associated with autosomal dominant deafness in a Brazilian family.
AB  - We ascertained a Brazilian family with nine individuals affected by autosomal
      dominant nonsyndromic sensorineural hearing loss. The bilateral hearing loss
      affected mainly mid-high frequencies, was apparently stable with an early onset.
      Microsatellites close to the DFNA8/DFNA12 locus, which harbors the TECTA gene,
      showed significant multipoint lod scores (3.2) close to marker D11S4107.
      Sequencing of the exons and exon-intron boundaries of the TECTA gene in one
      affected subject revealed the deletion c.5383+5delGTGA in the 5' end of intron
      16, that includes the last two bases of the donor splice site consensus sequence.
      This mutation segregates with deafness within the family. To date, 33 different
      TECTA mutations associated with autossomal dominant hearing loss have been
      described. Among them is the mutation reported herein, first described by
      Hildebrand et al. (2011) in a UK family. The audioprofiles from the UK and
      Brazilian families were similar. In order to investigate the transcripts produced
      by the mutated allele, we performed cDNA analysis of a lymphoblastoid cell line
      from an affected heterozygote with the c.5383+5delGTGA and a noncarrier from the
      same family. The analysis allowed us to identify an aberrant transcript with
      skipping of exon 16, without affecting the reading frame. One of the dominant
      TECTA mutations already described, a synonymous substitution in exon 16
      (c.5331G<A), was also shown to affect splicing, resulting in an aberrant
      transcript lacking exon 16. Despite the difference in the DNA level, both the
      synonymous substitution in exon 16 (c.5331G<A) and the mutation described herein
      affect splicing of exon 16, leading to its skipping. At the protein level they
      would have the same effect, an in-frame deletion of 37 amino-acids
      (p.S1758Y/G1759_N1795del) probably leading to an impaired function of the ZP
      domain. Thus, like the TECTA missense mutations associated with dominant hearing
      loss, the c.5383+5delGTGA mutation does not have an inactivating effect on the
      protein.

PMID- 22995354
TI  - Oblique step ulnar shortening osteotomy for management of posttraumatic ulnar
      impaction.
AB  - We describe an oblique step-cut osteotomy technique for ulnar shortening. The
      technique requires no special instrumentation. It requires only an eight-hole 3.5
      mm low-contact dynamic compression plate for fixation. Sixteen patients with
      posttraumatic ulnar impaction syndrome were treated. The average patient age was
      40 years. The mean followup duration was 8 (range, 3 to 28) months. No nonunions
      occurred. Two patients required hardware removal for symptomatic hardware.
      Fourteen of the 16 patients reported persistence of occasional pain with some
      activities, but only 10 had any pain elicited at the time of examination. One
      patient required revision of the ulnar shortening procedure for persistence of
      symptoms. Functional outcomes were comparable with ulnar shortening performed by
      other methods. However, this technique might offer improved union rates compared
      with those described in the literature and is applicable to treat ulnar impaction
      syndrome arising from other causes.

PMID- 22995355
TI  - Learning curve for the anterior approach total hip arthroplasty.
AB  - The anterior approach to total hip arthroplasty has the advantages of using
      intermuscular and internervous planes, but it is technically demanding. We
      evaluated the learning curve for this approach with regard to operative
      parameters and immediate outcomes. From November 2005 through May 2007, 73
      patients underwent 81 consecutive primary anterior-approach total hip
      arthroplasties. We grouped the hips into three consecutive groups of 20 and one
      of 21, and surgical and fluoroscopy times, estimated blood loss, intraoperative
      and postoperative complications, patient comorbidities, component position, and
      leg-length discrepancy were compared (statistical significance, p < 0.05).
      Comparing Groups 1 and 4, there were only two significant differences: operative
      time, 124 to 98 minutes, respectively, and estimated blood loss, 596 to 347 mL,
      respectively. Proficiency improved after Group 2 (40 cases) and was more marked
      after Group 3 (60 cases), with no major complications. Surgeons considering this
      approach should expect a substantial learning period.

PMID- 22995356
TI  - Ethyl chloride improves antiseptic effect of betadine skin preparation for office
      procedures.
AB  - To determine if ethyl chloride is an effective disinfectant alone or combined
      with povidone iodine in a clinical setting, 35 volunteers had different portions
      of their knees swabbed with sterile cotton-tip applicators after an area of skin
      was prepared with either ethyl chloride alone, povidone iodine alone, or povidone
      iodine followed by ethyl chloride. An area with no preparation at all served as
      the control. Specimens were then cultured on agar plates and bacterial growth
      assessed. When the data was categorized as colony forming units (CFUs) or no
      CFUs, both ethyl chloride and povidone iodine used alone had significantly fewer
      specimens with CFUs (p=0.001) than controls, but were not significantly different
      from each other (p=0.18). Additionally, the combination of povidone iodine
      followed by ethyl chloride spray had significantly fewer samples with CFUs than
      either product used alone (p=0.001). In addition to its local anesthetic
      properties, ethyl chloride may be an effective disinfectant alone and may improve
      skin disinfection when used with povidone iodine compared to povidone iodine
      alone.

PMID- 22995357
TI  - Publication rates of abstracts presented at the annual meeting of the Society of
      Military Orthopaedic Surgeons.
AB  - Previous studies have reported publication rates of abstracts presented at
      orthopaedic meetings from 22 to 68 percent. The objective of this study was to
      determine the publication rate of papers presented at the Society of Military
      Orthopaedic Surgeons (SOMOS) meetings from 1999 to 2003. A database was created
      including all abstracts presented at SOMOS meetings from 1999 to 2003 as listed
      in official program books. To assess whether each abstract resulted in
      publication in a peer-reviewed journal, a computerized PubMed search of the
      presenting author and appropriate keywords from the title was conducted. Overall,
      191 of the 435 abstracts presented at SOMOS from 1999 to 2003 were published in a
      peer-reviewed journal, giving a publication rate of 44%. The publication rate of
      abstract presentations at annual SOMOS meetings compares favorably with the rates
      for other orthopaedic meetings. However, less than 50% result in peer-reviewed
      publication.

PMID- 22995358
TI  - Quantification of radial torsion angle with computerized tomography: a clinical
      study.
AB  - Our objective is to assess the utility of the radial torsion angle (RTA) as
      described by Bindra et al. in the clinical setting among patients with previous
      distal radial fractures compared to normal controls [4]. We hypothesize that the
      side-to-side RTA difference will be increased in subjects with previous forearm
      fracture as compared to normal subjects. Nineteen patients with a history of
      distal radial fractures and five normal subjects underwent bilateral upper
      extremity computerized tomography (CT) scans between 1999 and 2006. The radial
      torsion angle and the side-to-side difference were calculated by two
      radiologists. Correlation was made between the RTA and the patient's forearm
      range of motion (ROM). Mean patient age was 37.8 +/- 14.2 years. Mean radial
      torsion angle was 49.3 +/- 22.4 degrees in the affected side and 36.7 +/- 13.8
      degrees in the unaffected side (p = 0.005). Mean side-to-side RTA was 18.4 +/- 10
      degrees in the cases versus 3.0 +/- 1.41 degrees in normal subjects (p < 0.0001).
      Kappa coefficient for the side-to-side RTA differences was 0.62 (good agreement).
      Eighteen out of the 19 patients underwent surgery, ten of which were osteotomies.
      There was a statistically significant increase in side-to-side difference in the
      RTA among patients compared to controls.

PMID- 22995359
TI  - Leiomyosarcoma of the somatic soft tissues.
AB  - Leiomyosarcomas of the somatic soft tissues are tumors of smooth muscle origin
      that occur in the extremities. These lesions are commonly high-grade tumors that
      carry a poor prognosis. Recommended treatment often includes wide excision and
      chemotherapy or radiation therapy. Sixty-five patients were followed for a mean
      of 4.1 years. The mean maximum tumor diameter was 7 cm, and approximately 70% of
      all patients had tumors deep to fascia. Including all stages of disease, the
      overall 1-, 2-, and 5-year survival rates were 91%, 87%, and 68%, respectively.
      Mitotic rate and tumor depth were significant predictors of development of
      recurrent disease and metastatic disease. Tumor size was another predictor of
      recurrent disease. The mitotic rate and AJCC stage were also important predictors
      of overall survival. Patients with deep lesions, histologic grade 3
      disease/higher mitotic rates, and advanced stage of disease had a poorer
      prognosis and thus were more likely to undergo adjuvant chemotherapy. Future
      clinical studies may help determine if knowledge of these predictors can help
      guide treatment and improve clinical outcomes.

PMID- 22995360
TI  - Computer-assisted reduction method for periprosthetic distal femur fracture.
AB  - The purpose of this case report is to describe a novel use of computer assistance
      in identifying and restoring the mechanical axis in the treatment of a
      periprosthetic distal femur fracture in a 76-year-old female patient with a total
      knee arthroplasty.

PMID- 22995361
TI  - Osteosarcoma invasion of the inferior vena cava and right atrium.
AB  - We present a woman with chondroblastic osteosarcoma of the left ilium extending
      to the L4 epidural space and invading the inferior vena cava and right atrium,
      misdiagnosed as deep venous thrombosis. After neoadjuvant chemotherapy, two stage
      resection was planned. During the anterior approach, a mass in the left common
      iliac vein and inferior vena cava was found and tumor thromboembolism was
      diagnosed. Frozen sections showed chondroblastic osteosarcoma. The patient denied
      further surgery and had palliative intensity modulated radiation therapy.

PMID- 22995363
TI  - Eosinophilic myocarditis in an adolescent: a case report and review of the
      literature.
AB  - Eosinophilic myocarditis is a rare disease occurring mainly in adulthood. It is
      generally known to be caused by autoimmune diseases, parasitic infections,
      hypersensitivity to drugs or substances, and after vaccinations. We describe the
      case of a 15-year-old adolescent, who presented initially with flu-like symptoms,
      as well as syncope. Subsequently, catecholaminergic treatment had to be
      initialised because of cardiac failure. Peripheral eosinophil count was normal at
      admission and at the time of endomyocardial biopsy. The biopsy, however, proved
      the diagnosis of eosinophilic myocarditis, but the causative agent remained
      unclear despite intensive diagnostic work-up. Cardiac magnetic resonance imaging
      showed signs of acute myocardial oedema and a delayed enhancement in the basal
      inferolateral segments consistent with acute myocarditis. Under treatment with
      corticosteroids, angiotensin-converting enzyme inhibitor, and warfarin, we
      accomplished a rapid and complete recovery of cardiac function and histology.
      This unique case of eosinophilic myocarditis is rare in childhood. The
      differential diagnosis and diagnostic pathway is discussed, and a review of the
      literature and therapeutic options based on the literature is performed.

PMID- 22995365
TI  - Evaluation of the cobas 4800 CT/NG Test for detecting Chlamydia trachomatis and
      Neisseria gonorrhoeae DNA in urogenital swabs and urine specimens.
AB  - We have evaluated 696 samples (488 swabs and 208 urine specimens) with the cobas
      4800 (c4800) CT/NG Test for the detection of Chlamydia trachomatis and Neisseria
      gonorrhoeae DNA in swab and urine specimens. c4800 results were compared with
      those obtained from COBAS AMPLICOR (CAM) CT/NG Test. Discordant results were
      reanalyzed with the MultiNA system and compared with clinical data. For C.
      trachomatis detection by both methods, we obtained 93.8%, 100%, 100%, and 99.1%
      for sensitivity, specificity, and positive and negative predictive values,
      respectively. For urine specimens analyzed in c4800, our results were 96.6%,
      100%, 100%, and 99.4%, respectively. For N. gonorrhoeae detection, swab results
      were:88.0%, 100%, 100%, and 99.4%. For urine specimen, results obtained were
      100%, 100%, 100%, and 100%. Reanalyses were all concordant between both methods.
      c4800 results were comparable with those obtained with the CAM system. We had an
      excellent correlation between swab and urine specimens analyzed by c4800.

PMID- 22995364
TI  - Aeromonas aquariorum septicemia and enterocolitis in a cirrhotic patient.
AB  - Aeromonas aquariorum is a recently described Aeromonas species. We present a
      cirrhotic patient with septicemia and bloody diarrhea in whom A. aquariorum was
      isolated from the blood and stool. The species identification was based on
      sequence analysis of the partial rpoB and rpoD genes. The A. aquariorum isolates
      carried genes encoding hemolysin, aerolysin, and the cytotonic enterotoxin Alt.
      Significant A. aquariorum-induced cytotoxicity in intestinal epithelial cells was
      also demonstrated.

PMID- 22995366
TI  - In vitro Etest synergy of doripenem with amikacin, colistin, and levofloxacin
      against Pseudomonas aeruginosa with defined carbapenem resistance mechanisms as
      determined by the Etest method.
AB  - The applicability of Etest for synergy testing was evaluated in 100 carbapenem
      nonsusceptible Pseudomonas aeruginosa isolates. Combinations of doripenem with
      amikacin, colistin, or levofloxacin were synergistic or additive against 67%,
      31%, and 23% of isolates, respectively. The use of Etest was practical to
      evaluate the synergy of doripenem with other antipseudomonal agents.

PMID- 22995367
TI  - Performance of surveillance cultures at different body sites to identify
      asymptomatic Staphylococcus aureus carriers.
AB  - The objective was to evaluate the performance of surveillance cultures at various
      body sites for Staphylococcus aureus colonization in pregnant women and newborns
      (NB) and the factors associated with nasal colonization. For NB, 4 sites were
      evaluated: nares, oropharynx, perineum, and umbilical stump (birth, third day,
      and weekly). For pregnant women, 4 sites during labor: anterior nares, anus,
      perineum, and oropharynx. Nasally colonized patients were compared with colonized
      only extranasally. Colonization was 53% of 392 pregnant women (methicillin
      resistant S. aureus [MRSA]: 4%) and 47% of 382 NB (MRSA: 9%). For newborn
      patients, the best body site was the umbilical stump (methicillin-susceptible S.
      aureus [MSSA]: 64%; MRSA: 68%) and the combination of nares + umbilical (MSSA:
      86%; MRSA: 91%). Among pregnant women, the best body site was the anterior nares
      (MSSA: 59%; MRSA: 67%) and the combination of nares + oropharynx (MSSA: 83%;
      MRSA: 80%). A smaller number of household members were associated with MRSA
      carriage in pregnant women (2.2 +/- 0.6 versus 3.6 +/- 1.8; P = 0.04). In
      conclusion, multiple culture sites are needed. Control programs based on
      surveillance cultures may be compromised.

PMID- 22995368
TI  - Quantitative changes of nicotinic receptors in the hippocampus of dystrophin
      deficient mice.
AB  - Lack of dystrophin in Duchenne muscle dystrophy (DMD) and in the mutant mdx mouse
      results in progressive muscle degeneration, structural changes at the
      neuromuscular junction, and destabilization of the nicotinic acetylcholine
      receptors (nAChRs). One-third of DMD patients also present non-progressive
      cognitive impairments. Considering the role of the cholinergic system in
      cognitive functions, the number of nAChR binding sites and the mRNA levels of
      alpha4, beta2, and alpha7 subunits were determined in brain regions normally
      enriched in dystrophin (cortex, hippocampus and cerebellum) of mdx mice using
      specific ligands and reverse-transcription polymerase chain reaction assays,
      respectively. Membrane preparations of these brain regions were obtained from
      male control and mdx mice at 4 and 12 months of age. The number of [3H]-cytisine
      (alpha4beta2) and [125I]-alpha-bungarotoxin ([125I]-alphaBGT, alpha7) binding
      sites in the cortex and cerebellum was not altered with age or among age-matched
      control and mdx mice. A significant reduction in [3H]-cytisine (48%) and [125I]
      alphaBGT (37%) binding sites was detected in the hippocampus of mdx mice at 12
      months of age. When compared with the age-matched control groups, the mdx mice
      did not have significantly altered [3H]-cytisine binding in the hippocampus, but
      [125I]-alphaBGT binding in the same brain region was 52% higher at 4 months and
      20% lower at 12 months. mRNA transcripts for the nAChR alpha4, beta2, and alpha7
      subunits were not significantly altered in the same brain regions of all animal
      groups. These results suggest a potential alteration of the nicotinic cholinergic
      function in the hippocampus of dystrophin-deficient mice, which might contribute
      to the impairments in cognitive functions, such as learning and memory, that have
      been reported in the dystrophic murine model and DMD patients.

PMID- 22995369
TI  - Effects of resveratrol on blood homocysteine level, on homocysteine induced
      oxidative stress, apoptosis and cognitive dysfunctions in rats.
AB  - We aimed to examine the protective effects of resveratrol against homocysteine
      induced oxidative stress, apoptosis and cognitive impairment. Rats were randomly
      divided into three groups. Control group received standard rat food; homocysteine
      group (Hcy group) received daily methionine at a dose of 1g/kg-body weight
      dissolved in drinking water for thirty days; third group (Hcy+Res group) received
      same amount of methionine plus 20mg/kg/day resveratrol intraperitoneally for
      thirty days. Cognitive performances of the animals were tested by Morris water
      maze test. Then all animals were sacrificed to study lipid peroxidation (LPO),
      DNA fragmentation and p53 mRNA expression in the rat brain. The aortas of the
      sacrificed rats were processed for histopathological examination. Apoptosis in
      the aortas was assessed by TUNEL staining. Resveratrol significantly decreased
      serum levels of homocysteine, reversed Hcy induced LPO increase, decreased DNA
      fragmentation and p53 mRNA expression in the rat brains, and improved
      homocysteine induced impairment of long term spatial memory. Resveratrol could
      inhibit homocysteine induced apoptosis and histopathological deterioration in the
      rat aortic sections. In conclusion, resveratrol is effective in preventing
      homocysteine induced vascular and neural defects. In hyperhomocysteinemic rat
      model, our findings consequently warrant in future studies to reveal the true
      improvement mechanism of resveratrol.

PMID- 22995370
TI  - Preventive medicine and diet-related diseases: searching for impact.

PMID- 22995372
TI  - State legislators' support for evidence-based obesity reduction policies.
AB  - OBJECTIVE: This study aimed to gauge state legislators' level of support for
      evidence-based obesity reduction policies. METHODS: A list of 17 potential
      obesity reduction measures was sent via a valid and reliable survey questionnaire
      to a random sample of 800 state legislators from all 50 United States in 2011.
      Legislators were asked to rate their support for each measure on a three-point
      Likert-type scale. RESULTS: There were 250 questionnaires returned. Chi-square
      tests revealed no significant differences between respondents and non-respondents
      by sex, political affiliation, or chamber designation. Respondents were
      approximately evenly split between Republicans (n=117) and Democrats (n=122).
      Overall, public school and community-based measures were supported at
      approximately the same levels. Linear regression revealed that political
      affiliation, race, and perceiving obesity as a serious societal problem were
      significant predictors of legislator support for obesity reduction policies.
      Legislator body mass index, level of education, and geographic location were not
      significant predictors of support. CONCLUSIONS: Public health advocates
      interested in promoting obesity prevention legislation at the state level are
      most likely to find support among non-white female Democratic legislators
      regardless of their BMI who perceive obesity to be a serious societal problem.

PMID- 22995371
TI  - Weight status and weight-related behaviors of children commencing school.
AB  - OBJECTIVE: To describe the weight status and weight-related behaviors of children
      commencing school. METHODS: This study is a representative cross-sectional survey
      of Australian children in their first year of schooling (n=1141) in 2010. Height
      and weight were measured, and parents reported their child's diet, physical
      activity and screen-time. RESULTS: 18.7% of children were overweight/obese.
      Compared with non-overweight/obese peers, overweight/obese boys were 1.73 times
      (95% CI 1.08, 2.79) as likely to exceed recommended screen time and 2.07 times
      (95% CI 1.11, 3.87) as likely to eat dinner three or more times/week in front of
      the TV. Overweight/obese girls were twice as likely to have a TV in their bedroom
      (OR 2.00, 95% CI 1.12, 3.59) and usually be rewarded with sweets for good
      behavior (OR 1.96, 95% CI 1.09, 3.51) and were 1.65 times as likely to be
      inactive (95% CI 1.08, 2.55). CONCLUSION: We showed that many children begin
      school with established weight-related behaviors that occur in the home
      environment. The inclusion of parents and the home environment in intervention
      strategies will be important to support changes to reduce childhood obesity. The
      weight status and weight-related behaviors of children entering school may
      potentially be a general indicator of the overall effectiveness of obesity
      prevention interventions among preschool-aged children.

PMID- 22995374
TI  - [Preliminary study of laparoscopic cholecystectomy in Cameroon].
AB  - AIM: The purpose of this study was to evaluate the feasibility of laparoscopic
      cholecystectomy in Cameroon. MATERIALS AND METHOD: This retrospective study
      includes all patients who underwent laparoscopic cholecystectomy in three major
      hospitals in Cameroon from 2001 to 2009. Charts were reviewed for epidemiological
      data, complications, and outcome. RESULTS: This study included 52 patients. Their
      mean age was 45 years (range: 17-71). All had symptomatic gallstones, and 15
      presented acute cholecystitis. The rate of conversion to open surgery was 7.7%.
      No deaths occurred. One patient required reoperation due to cystic duct stump
      leakage complicated by biliary peritonitis. The average duration of
      hospitalization was 3 days. CONCLUSION: Based on these results, we recommend
      laparoscopic cholecystectomy for symptomatic gallstones in Cameroon.

PMID- 22995373
TI  - Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl
      2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign,
      borderline, and malignant serous and mucinous ovarian tumors.
AB  - BACKGROUND: In many tumors including ovarian cancer, cell proliferation and
      apoptosis are important in pathogenesis and there are many alterations in most of
      the genes related to the cell cycle. This study was designed to evaluate
      immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and
      bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in typing of
      benign, borderline, and malignant serous and mucinous ovarian tumors. METHODS:
      Total of 68 ovarian tumors, 25 benign [13 (19.1%) serous and 12 (17.6%)
      mucinous], 16 borderline [9 (13.2%) serous and 7(10.3%) mucinous], and 27
      malignant ovarian tumors [24 (35.3%) serous and 3 (4.4%) mucinous tumors] were
      included in the study. Immunohistochemical expression of p53, p21, bax, bcl-2,
      telomerase, c-kit, and metallothionein were evaluated. RESULTS: When all 68 cases
      were evaluated as benign, borderline, and malignant ovarian tumors without
      considering histopathological subtypes, the p53, p21, bax and metallothionein
      showed significantly higher staining scores in the borderline and malignant ones
      (p < 0.05). After evaluation of all 68 cases, the serous tumors showed
      significantly higher staining scores of p53, p21, c-kit, and metallothionein
      compared to the mucinous ones (p < 0.05). For differentiation of benign and
      borderline and malignant tumors combined, p53 was not used because all benign
      tumors has no staining, and p21, bax, and metallothionein was determined the
      significant predictors for borderline and malignant tumors combined (p < 0.05).
      For differentiation of borderline and malignant tumors, only p53 was determined
      the significant predictor for malignant tumors (p < 0.05). CONCLUSIONS: In
      conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the
      typing of ovarian tumors as benign, borderline and malignant or serous and
      mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in
      the pathogenesis of ovarian tumor types. p53 and metallothionein may be helpful
      in the typing of borderline and malignant ovarian tumors. The immunohistochemical
      staining with bcl-2 and telomerase may not provide meaningful contribution for
      the typing of ovarian tumors. VIRTUAL SLIDE: The virtual slides for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2013030833768498.

PMID- 22995375
TI  - Comparison of magnetic carboxymethyl chitosan nanoparticles and cation exchange
      resin for the efficient purification of lysine-tagged small ubiquitin-like
      modifier protease.
AB  - A fusion tag that can be purified by the cheap ion-exchanger based on the ionic
      binding force may provide a cost-effective scheme over other affinity fusion
      tags. Small ubiquitin-like modifier (SUMO) protease derived from Saccharomyces
      cerevisiae was fused with a poly lysine tag containing 10 lysine residues at its
      C-terminus and then expressed in Escherichia coli. The ionic binding force
      provided by the ploy lysine tag allowed the selective recovery of the small
      ubiquitin-like modifier protease from recombinant E. coli cell extracts. A
      preliminary comparative study of the adsorption and elution of poly lysine tagged
      SUMO protease on Amberlite Cobalamion and magnetite carboxymethyl chitosan
      nanoparticles was performed. Amberlite Cobalamion and magnetite nanoparticles had
      the similar elution profile due to the common functional groups - carboxyl
      groups. The maximum dynamic adsorption capacity of Amberlite Cobalamion and
      magnetite nanoparticles reached 36.8 and 211.4 mg/g, respectively. The lysine
      tagged protease can be simply purified by magnetite nanoparticles from cell
      extracts with higher purity than that by Amberlite Cobalamion. The
      superparamagnetic nanoparticles possess the advantages of highly specific, fast
      and excellent binding of a larger amount of lysine tagged SUMO modifier protease,
      and it is also easier to separate from the crude biological process liquors
      compared with the conventional separation techniques of polycationic amino acids
      fusion proteins.

PMID- 22995376
TI  - Determination of glutamate uptake by high performance liquid chromatography
      (HPLC) in preparations of retinal tissue.
AB  - The present study describes a simple and efficient method utilizing high
      performance liquid chromatography (HPLC) coupled to fluorescence detection for
      the determination of kinetic parameters of glutamate uptake in nervous tissue.
      Retinal tissue obtained from 7-day-old chicks was incubated with known
      concentrations of glutamate (50-2000 MUM) for 10 min, and the levels of the o
      phtaldehyde (OPA)-derivatized neurotransmitter in the incubation medium were
      measured. By assessing the difference between initial and final concentrations of
      glutamate in the medium, a saturable uptake mechanism was characterized (K(m)=8.2
      and V(max)=9.8 nmol/mg protein/min). This measure was largely sodium- and
      temperature-dependent, strongly supporting that the mechanism for concentration
      decrements is indeed uptake by high-affinity transporters. Added to this, our
      results also demonstrated that zinc chloride (an inhibitor of glutamate/aspartate
      transporters) evoked a concentration-dependent decrease in glutamate uptake,
      demonstrating the specificity of our methodology. Overall, the present work
      characterizes an alternative methodology to evaluate glutamate uptake in nervous
      tissue using HPLC. This approach could be an important tool for studies
      associated to the characterization of minute alterations in glutamate transport
      related with central nervous system injury.

PMID- 22995377
TI  - Liquid chromatography-tandem mass spectrometry method for quantification of
      thymidine kinase activity in human serum by monitoring the conversion of 3'-deoxy
      3'-fluorothymidine to 3'-deoxy-3'-fluorothymidine monophosphate.
AB  - Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis whose activity in
      serum is indicative of tumor proliferation and the severity of blood
      malignancies. 3'-deoxy-3'-fluorothymidine (FLT), a specific exogenous substrate
      for TK1, is phosphorylated by TK1 in the presence of a phosphorylating buffer,
      therefore the conversion of FLT to 3'-deoxy-3'-fluorothymidine monophosphate (FLT
      MP) can be measured to assess serum TK1 activity. Here we describe a liquid
      chromatography-MS/MS (LC-MS/MS) method for quantification of FLT and FLT-MP from
      serum using protein precipitation and column switching followed by detection on
      an Applied Biosystems SCIEX API 4000 QTrap mass spectrometer. The method was
      linear over the range of 0.5-500 ng/mL for FLT and 2.5-2000 ng/mL for FLT-MP with
      a mean correlation coefficient of 0.9964 and 0.9935 for FLT and FLT-MP,
      respectively. The lower limit of quantification was 0.5 ng/mL for FLT and 2.5
      ng/mL for FLT-MP. Intra-assay accuracy and inter-assay accuracy was within +/-12%
      for both FLT and FLT-MP. Intra-assay precision was 2.8% to 7.7% for FLT and 3.3%
      to 5.8% for FLT-MP. Inter-assay precision was 4.6% to 14.9% for FLT and 4.9% to
      14.6% for FLT-MP. Serum TK1 activity was measured in serum from hepatocellular
      carcinoma patients and age-matched controls under standardized conditions.
      Elevated TK1 activity was detected in 26.3% of hepatocellular carcinoma samples
      compared to controls. This method provides a robust alternative to radiometric
      and immunochemical assays of serum TK1 activity.

PMID- 22995378
TI  - Hippocampal magnetic resonance imaging abnormalities in cardiac arrest are
      associated with poor outcome.
AB  - BACKGROUND: The role of neuroimaging in assessing prognosis in comatose cardiac
      survivors appears promising, but little is known regarding the import of
      particular spatial patterns. We report a specific spatial imaging abnormality on
      magnetic resonance imaging (MRI) that portends a poor prognosis: bilateral
      hippocampal hyperintensities on diffusion-weighted imaging (DWI) and fluid
      attenuated inversion recovery (FLAIR) sequences. METHODS: Eighty sequential
      comatose cardiac arrest patients underwent MRI scans. Qualitative and
      quantitative regional analyses were performed. Patients were categorized as
      HIPPO(+) (n = 18) or HIPPO(-) (n = 62) based on whether they had bilateral
      hippocampal hyperintensities. Poor outcome was defined by a modified Rankin Scale
      (mRS) score >=4 at 6 months. RESULTS: Patients with bilateral hippocampal
      abnormalities had a higher frequency of poor outcome (P = .032). HIPPO(+)
      patients suffered more severe cerebral injury, with lower whole brain apparent
      diffusion coefficient values (P = .043) and a greater number of affected regions
      on DWI (P = .001) and FLAIR (P = .001) than HIPPO(-) patients. The hippocampal
      approach was 100% specific for a poor prognosis; only 1 patient survived and
      remained in a vegetative state. CONCLUSIONS: Bilateral hippocampal
      hyperintensities on MRI may be a specific imaging finding that is indicative of
      poor prognosis in patients who suffer global hypoxic-ischemic injury. More
      research on the prognostic significance of this and similar neuroimaging patterns
      is indicated.

PMID- 22995379
TI  - Validation of the 12-item stroke-specific quality of life scale in a biethnic
      stroke population.
AB  - The 12-item Stroke-Specific Quality of Life Scale (SSQOL), a shortened version of
      the original SSQOL, was developed to be an efficient and valid outcome in stroke
      research. We aimed to assess the validity of this scale in a biethnic ischemic
      stroke population. Patients with validated ischemic stroke who completed the
      original 49-item SSQOL at 90 days poststroke were identified from a population
      based study, the Brain Attack Surveillance in Corpus Christi Project. Cronbach's
      alpha was used to assess the internal consistency of the scales. Intraclass
      correlation coefficients and linear regression were used to assess agreement
      between the 2 scales. The study cohort comprised 45 patients with ischemic
      stroke, 56% female and 51% Mexican American, with a mean age of 66.0+/-11.3
      years. The mean score for the 49-item scale was 3.33+/-0.84, compared with 3.31+/
      0.95 for the 12-item scale. Internal consistency was 0.96 for the 49-item scale
      and 0.88 for the 12-item scale. The 2 scales were highly correlated (intraclass
      correlation coefficient, 0.98; R2=0.97). This study in patients with ischemic
      stroke from diverse racial/ethnic backgrounds found that the more efficient 12
      item SSQOL is a valid alternative to the full 49-item SSQOL for the assessment of
      health-related quality of life.

PMID- 22995380
TI  - The essential can be invisible to the eyes: the "fogging effect" phenomenon in
      the subacute stage of ischemic stroke.
AB  - Cerebral infarcts can be overlooked or grossly underestimated in the second and
      third week after an ischemic stroke. We report a patient who presented with a
      vanishing stroke on a follow-up brain computed tomography scan, a condition known
      as the "fogging effect" phenomenon. 

PMID- 22995381
TI  - Why we do not have--and will not have--the integrated and "smart" alarm systems
      that technology would allow us to have today.
AB  - BACKGROUND: Many authors have been advocating "smart alarm systems" for more than
      30 years, and technology for such systems has been described in the literature
      for more than 20 years. Such systems do not exist today. GOALS: Incoming data
      would be analyzed to reject artifact. Multiple inputs would be used to determine
      alarm conditions. Information would be passed to the best person to address the
      problem. If the primary person failed to respond, a backup person would be
      notified. THE PROBLEM: One might show a statistical improvement in patient
      outcome with a new system, but there would always be patients who would have had
      an alarm under the old system, and who did not have an alarm with the new system.
      Only if Congress would exempt the alarm integrators from liability, as the
      vaccine makers are protected, could such a system be built.

PMID- 22995382
TI  - Automated serial ECG comparison improves computerized interpretation of 12-lead
      ECG.
AB  - BACKGROUND: Interpretation of a patient's 12-lead ECG frequently involves
      comparison to a previously recorded ECG. Automated serial ECG comparison can be
      helpful not only to note significant ECG changes but also to improve the single
      ECG interpretation. Corrections from the previous ECG are carried forward by the
      serial comparison algorithm when measurements do not change significantly.
      METHODS: A sample of patients from three hospitals was collected with two or more
      12-lead ECGs from each patient. There were 233 serial comparisons from 143
      patients. 41% of patients had two ECGs and 59% of patients had more than two
      ECGs. ECGs were taken from a difficult population as measured by ECG
      abnormalities, 197/233 abnormal, 11/233 borderline, 14/233 otherwise-normal and
      11/233 normal. ECGs were processed with the Philips DXL algorithm and then in
      time order for each patient with the Philips serial comparison algorithm. To
      measure accuracy of interpretation and serial change, an expert cardiologist
      corrected the ECGs in stages. The first ECG was corrected and used as the
      reference for the second ECG. The second ECG was then corrected and used as the
      reference for the third ECG and so on. At each stage, the serial comparison
      algorithm compared an unedited ECG to an earlier edited ECG. Interpretation
      accuracy was measured by comparing the algorithm to the cardiologist on a
      statement by statement basis. The effect of serial comparison was measured by the
      sum of interpretive statement mismatches between the algorithm and cardiologist.
      Statement mismatches were measured in two ways, (1) exact match and (2) match
      within the same diagnostic category. RESULTS: The cardiologist used 910
      statements over 233 ECGs for an average number of 3.9 statements per ECG and a
      mode of 4 statements. When automated serial comparison was used, the total number
      of exact statement mismatches decreased by 29% and the total same-category
      statement mismatches decreased by 47%. CONCLUSION: Automated serial comparison
      improves interpretation accuracy in addition to its main role of noting
      differences between ECGs.

PMID- 22995383
TI  - QT variability paradox after premature ventricular contraction in patients with
      structural heart disease and ventricular arrhythmias.
AB  - BACKGROUND: Increased repolarization lability is known to be associated with the
      risk of ventricular tachycardia (VT)/ventricular fibrillation (VF). Premature
      ventricular contractions (PVCs) are excluded from the analysis of QT variability.
      However, QT dynamics after PVCs is poorly understood. METHODS: We analyzed data
      of 33 patients with structural heart disease (mean age 60.5 +/- 12.1; 24 (73%)
      men; 26 (79%) whites; 22 (67%) ischemic cardiomyopathy) and single-chamber ICD
      implanted for primary (28 patients, 85%) or secondary prevention of SCD.
      Arrhythmia group comprised 16 patients with VT/VF/death outcomes. Alive patients
      (n = 17) without VT/VF served as controls. The baseline far-field (FF) ICD
      electrogram (EGM) was recorded at rest. RR and QT intervals of 15 sinus beats
      before and after PVC in 33 patients were analyzed. The prematurity index,
      C(i)Mean(RR), where C(i) is coupling interval, was used to select the most
      premature PVC. QT variability index (QTVI) was calculated. Difference in QTVI was
      calculated as QTVI(diff) = QTVI(after)-QTVI(before.) RESULTS: In paired analysis
      QTVI significantly increased after PVC in controls (0.64 +/- 1.02 vs. 0.26 +/-
      1.15; P = 0.046), but decreased in patients in the arrhythmia group (0.16 +/-
      0.85 vs. 0.43 +/- 0.84; P = 0.190). QTVI(diff) was significantly lower in
      patients with VT/VF, as compared to controls (-0.197 +/- 0.650 vs. 0.207 +/-
      0.723; P=0.030). In multivariate logistic regression after adjustment for the
      type of cardiomyopathy and NYHA class the decrease in QTVI after PVC was
      associated with increased risk of VT/VF (OR 9.24; 95% CI 1.11-76.82; P=0.040).
      CONCLUSION: Elevated at baseline QTVI is decreased during first 15 beats after
      PVC in patients at risk for VT/VF.

PMID- 22995384
TI  - Purple sweet potato color attenuates hepatic insulin resistance via blocking
      oxidative stress and endoplasmic reticulum stress in high-fat-diet-treated mice.
AB  - Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins,
      has been reported to possess a variety of health-promoting properties. Emerging
      evidence indicates that PSPC can suppress postprandial hyperglycemia via
      inhibition of alpha-glucosidases. However, the protective effects of PSPC on
      hepatic insulin resistance and the precise mechanisms underlying these protective
      effects have never been investigated. In this study, our data showed that PSPC
      effectively improved the fasting blood glucose level, glucose and insulin
      tolerance by suppressing reactive oxygen species (ROS) production and by
      restoring glutathione (GSH) content and antioxidant enzymes' activities. PSPC
      further prevented the oxidative-stress-mediated endoplasmic reticulum (ER) stress
      in the livers of high-fat-diet (HFD)-treated mice. Moreover, PSPC dramatically
      suppressed the c-Jun-N-terminal kinase 1 and I kappa B kinase beta activation and
      nuclear factor-kappa B p65 nuclear translocation caused by oxidative and ER
      stress in the livers of HFD-treated mice. Ultimately, PSPC notably restored the
      impairment of the insulin receptor substrate-1/phosphoinositide 3 kinase/protein
      kinase B (Akt) insulin signaling in the livers of HFD-treated mice. In
      conclusion, our findings indicate that PSPC protected against HFD-induced hepatic
      insulin resistance via decreasing ROS level and blocking ROS-mediated ER stress.

PMID- 22995385
TI  - Dietary abscisic acid ameliorates influenza-virus-associated disease and
      pulmonary immunopathology through a PPARgamma-dependent mechanism.
AB  - The anti-inflammatory phytohormone abscisic acid (ABA) modulates immune and
      inflammatory responses in mouse models of colitis and obesity. ABA has been
      identified as a ligand of lanthionine synthetase C-like 2, a novel therapeutic
      target upstream of the peroxisome proliferator-activated receptor gamma
      (PPARgamma) pathway. The goal of this study was to investigate the immune
      modulatory mechanisms underlying the anti-inflammatory efficacy of ABA against
      influenza-associated pulmonary inflammation. Wild-type (WT) and conditional
      knockout mice with defective PPARgamma expression in lung epithelial and
      hematopoietic cells (cKO) treated orally with or without ABA (100 mg/kg diet)
      were challenged with influenza A/Udorn (H3N2) to assess ABA's impact in disease,
      lung lesions and gene expression. Dietary ABA ameliorated disease activity and
      lung inflammatory pathology, accelerated recovery and increased survival in WT
      mice. ABA suppressed leukocyte infiltration and monocyte chemotactic protein 1
      mRNA expression in WT mice through PPARgamma since this effect was abrogated in
      cKO mice. ABA ameliorated disease when administered therapeutically on the same
      day of the infection to WT but not mice lacking PPARgamma in myeloid cells. We
      also show that ABA's greater impact is between days 7 and 10 postchallenge when
      it regulates the expression of genes involved in resolution, like 5-lipoxygenase
      and other members of the 5-lipoxygenase pathway. Furthermore, ABA significantly
      increased the expression of the immunoregulatory cytokine interleukin-10 in WT
      mice. Our results show that ABA, given preventively or therapeutically,
      ameliorates influenza-virus-induced pathology by activating PPARgamma in
      pulmonary immune cells, suppressing initial proinflammatory responses and
      promoting resolution.

PMID- 22995386
TI  - Retention of bone strength by feeding of milk and dairy products in
      ovariectomized rats: involvement of changes in serum levels of 1alpha, 25(OH)2D3
      and FGF23.
AB  - The current study compared the effects of milk, yogurt or whey on the bone
      strength, body composition and serum biomarkers. Forty 12-week-old female Sprague
      Dawley rats were ovariectomized (OVX), and another nine rats received a sham
      operation (Sham-Cont). After a 1-week recovery period, the OVX rats were divided
      into four dietary groups: OVX-control group (OVX-Cont), 17% skimmed milk powder
      diet group (OVX-Milk), 17% powdered fermented milk diet group (OVX-Yogurt) and
      12% whey powder and 6% whey protein extract diet group (OVX-Whey) (n=10 in each
      group). The protein, nitrogen, fat, calcium and phosphorus contents of the
      experimental diets were adjusted to be similar to the control diet (AIN-93M).
      Eighty-four days after the beginning of the experimental diet, the total bone
      mineral density and bone mineral contents of lumbar vertebrae were significantly
      higher in the OVX-Milk and OVX-Whey groups than in the OVX-Cont group.
      Furthermore, the level of 1alpha, 25-dihydroxyvitamin D3 [1alpha, 25(OH)2D3] was
      significantly lower, while the serum level of FGF23 was significantly higher in
      the OVX-Milk, OVX-Yogurt and OVX-Whey groups than in the OVX-Cont group. These
      findings suggest that milk and the dairy products could improve bone metabolism
      in a postmenopausal animal model at least partly through changing the balance
      between 1alpha, 25(OH)2D3 and FGF23.

PMID- 22995387
TI  - Grape seed procyanidins improve beta-cell functionality under lipotoxic
      conditions due to their lipid-lowering effect.
AB  - Procyanidins have positive effects on glucose metabolism in conditions involving
      slightly disrupted glucose homeostasis, but it is not clear how procyanidins
      interact with beta-cells. In this work, we evaluate the effects of procyanidins
      on beta-cell functionality under an insulin-resistance condition. After 13 weeks
      of cafeteria diet, female Wistar rats were treated with 25 mg of grape seed
      procyanidin extract (GSPE)/kg of body weight (BW) for 30 days. To determine the
      possible mechanisms of action of procyanidins, INS-1E cells were separately
      incubated in high-glucose, high-insulin and high-oleate media to reproduce the
      conditions the beta-cells were subjected to during the cafeteria diet feeding. In
      vivo experiments showed that chronic GSPE treatment decreased insulin production,
      since C-peptide levels and insulin protein levels in plasma were lower than those
      of cafeteria-fed rats, as were insulin and Pdx1 mRNA levels in the pancreas. GSPE
      effects observed in vivo were reproduced in INS-1E cells cultured with high
      oleate for 3 days. GSPE treatment significantly reduces triglyceride content in
      beta-cells treated with high oleate and in the pancreas of cafeteria-fed rats.
      Moreover, gene expression analysis of the pancreas of cafeteria-fed rats revealed
      that procyanidins up-regulated the expression of Cpt1a and down-regulated the
      expression of lipid synthesis-related genes such as Fasn and Srebf1. Procyanidin
      treatment counteracted the decrease of AMPK protein levels after cafeteria
      treatment. Procyanidins cause a lack of triglyceride accumulation in beta-cells.
      This counteracts its negative effects on insulin production, allowing for healthy
      levels of insulin production under hyperlipidemic conditions.

PMID- 22995388
TI  - Anthocyanin-enriched bilberry and blackcurrant extracts modulate amyloid
      precursor protein processing and alleviate behavioral abnormalities in the
      APP/PS1 mouse model of Alzheimer's disease.
AB  - A growing body of epidemiological evidence suggests that fruit and vegetable
      juices containing various phenolic compounds can reduce the risk of Alzheimer's
      disease (AD). As the altered amyloid precursor protein (APP) processing leading
      to increased beta-amyloid (Abeta) production is a key pathogenic feature of AD,
      we elucidated the effects of different polyphenols on neuroprotection and APP
      processing under different in vitro stress conditions. The effects of these
      compounds were also investigated in transgenic AD mice (APdE9). Free radical
      toxicity and apoptosis were induced in human SH-SY5Y neuroblastoma cells
      overexpressing APP751. Menadione-induced production of reactive oxygen species
      was significantly decreased upon treatment with myricetin, quercetin or
      anthocyanin-rich extracts in a dose-dependent manner. However, these extracts did
      not affect caspase-3 activation, APP processing or Abeta levels upon
      staurosporine-induced apoptosis. APdE9 mice fed with anthocyanin-rich bilberry or
      blackcurrant extracts showed decreased APP C-terminal fragment levels in the
      cerebral cortex as compared to APdE9 mice on the control diet. Soluble Abeta40
      and Abeta42 levels were significantly decreased in bilberry-fed mice as compared
      to blackcurrant-fed mice. Conversely, the ratio of insoluble Abeta42/40 was
      significantly decreased in blackcurrant-fed mice relative to bilberry-fed mice.
      Both berry diets alleviated the spatial working memory deficit of aged APdE9 mice
      as compared to mice on the control diet. There were no changes in the expression
      or phosphorylation status of tau in APdE9 mice with respect to diet. These data
      suggest that anthocyanin-rich bilberry and blackcurrant diets favorably modulate
      APP processing and alleviate behavioral abnormalities in a mouse model of AD.

PMID- 22995389
TI  - Biochemical and metabolic mechanisms by which dietary whey protein may combat
      obesity and Type 2 diabetes.
AB  - Consumption of milk and dairy products has been associated with reduced risk of
      metabolic disorders and cardiovascular disease. Milk contains two primary sources
      of protein, casein (80%) and whey (20%). Recently, the beneficial physiological
      effects of whey protein on the control of food intake and glucose metabolism have
      been reported. Studies have shown an insulinotropic and glucose-lowering
      properties of whey protein in healthy and Type 2 diabetes subjects. Whey protein
      seems to induce these effects via bioactive peptides and amino acids generated
      during its gastrointestinal digestion. These amino acids and peptides stimulate
      the release of several gut hormones, such as cholecystokinin, peptide YY and the
      incretins gastric inhibitory peptide and glucagon-like peptide 1 that potentiate
      insulin secretion from beta-cells and are associated with regulation of food
      intake. The bioactive peptides generated from whey protein may also serve as
      endogenous inhibitors of dipeptidyl peptidase-4 (DPP-4) in the proximal gut,
      preventing incretin degradation. Indeed, recently, DPP-4 inhibitors were
      identified in whey protein hydrolysates. This review will focus on the emerging
      properties of whey protein and its potential clinical application for obesity and
      Type 2 diabetes.

PMID- 22995390
TI  - Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal
      fluid stroke volume.
AB  - This study identifies a novel relationship between cerebrospinal fluid (CSF)
      stroke volume through the cerebral aqueduct and the characteristic peaks of the
      intracranial pulse (ICP) waveform. ICP waveform analysis has become much more
      advanced in recent years; however, clinical practice remains restricted to mean
      ICP, mainly due to the lack of physiological understanding of the ICP waveform.
      Therefore, the present study set out to shed some light on the physiological
      meaning of ICP morphological metrics derived by the morphological clustering and
      analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating
      their relationships with a well defined physiological variable, i.e., the stroke
      volume of CSF through the cerebral aqueduct. Seven patients received both
      overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral
      aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological
      analysis of the ICP signal was performed by the MOCAIP algorithm. Following
      extraction of morphological metrics from the ICP signal, nine temporal ICP
      metrics and two amplitude-based metrics were compared with the ASV via Spearman's
      rank correlation. Of the nine temporal metrics correlated with the ASV, only the
      width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP
      pulse pressure amplitude and mean ICP did not reach significance. In this study,
      we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is
      positively related to the volume of CSF movement through the cerebral aqueduct.
      This finding is an initial step in bridging the gap between ICP waveform
      morphology research and clinical practice.

PMID- 22995391
TI  - Blocking beta-adrenergic signaling attenuates reductions in circulating leptin,
      cancellous bone mass, and marrow adiposity seen with dietary energy restriction.
AB  - We tested whether beta-adrenergic blockade attenuates bone loss and increased
      marrow adiposity during energy restriction (ER) and whether such an effect is
      associated with changes in serum leptin and leptin expression in bone and marrow
      tissues. Female 4-mo-old Sprague-Dawley rats were assigned into four groups (n =
      10 each): two groups of 40% ER treated with vehicle (ERVEH; saline) or beta
      blocker (ERBB; DL-propranolol; 250 MUg . kg(-1) . h(-1)) during 12 wk, and two
      groups of ad libitum-fed controls treated with the same two agents (CONVEH,
      CONBB, respectively). Over 84 days, CONVEH and CONBB rats gained but ERVEH and
      ERBB rats lost body fat mass; lean mass did not change in any group. Reduction in
      serum leptin in ERVEH rats was mitigated in ERBB rats (-5.32 vs. -1.15 ng/ml,
      respectively). The decline in proximal tibia cancellous vBMD observed in ERVEH
      rats was attenuated in ERBB rats (-85.24 vs. -53.94 mg/cm(3), respectively).
      Adipocyte number in ERVEH rats was dramatically higher vs. CON rats at week 12,
      but this increment was abolished by beta-blockade in ERBB animals. The number of
      osteoblastic cells and marrow adipocytes staining positively for leptin in ERVEH
      rats tended to be lower vs. that of both CON groups, but beta-blockade appears to
      reverse this effect in ERBB rats. In summary, beta-adrenergic blockade mitigated
      metaphyseal bone loss and bone marrow adiposity during energy restriction and
      attenuated reductions in serum leptin. These data suggest an important role for
      beta-adrenoreceptor signaling pathway in the cancellous bone and marrow fat
      response to energy restriction.

PMID- 22995393
TI  - Diaphragm efficiency estimated as power output relative to activation in chronic
      obstructive pulmonary disease.
AB  - Muscle efficiency increases with fiber length and decreases with load. Diaphragm
      efficiency (Eff(di)) in healthy humans, measured as power output (Wdi) relative
      to the root mean square of diaphragm electromyogram (RMS(di)), increases with
      hyperpnea due to phasic activity of abdominal muscles acting to increase
      diaphragm length at end expiration (L(di ee)) and decrease inspiratory load. In
      chronic obstructive pulmonary disease (COPD), hyperpnea may decrease Eff(di) if
      L(di ee) decreases and load increases due to airflow obstruction and dynamic
      hyperinflation. To examine this hypothesis, we measured Eff(di) in six COPD
      subjects (mean forced expiratory volume in 1 s: 54% predicted) when breathing air
      and at intervals during progressive hypercapnic hyperpnea. Wdi was measured as
      the product of mean inspiratory transdiaphragmatic pressure (DeltaPdi(mean)),
      diaphragm tidal volume measured fluoroscopically, and 1/inspiratory duration.
      Results were compared with those of six healthy subjects reported previously. In
      COPD, L(di ee) was normal when breathing air. DeltaPdi(mean) and Wdi increased
      normally, and RMS(di) increased disproportionately (P = 0.01) with hyperpnea,
      and, unlike health, inspiratory capacity (IC), L(di ee), and Eff(di) did not
      increase. IC and L(di ee) were constant with hyperpnea because mean expiratory
      flow increased as expiratory duration decreased (r(2) = 0.65), and because
      expiratory flow was terminated actively by the balance between expiratory and
      inspiratory muscle forces near end expiration, and these forces increased
      proportionately with hyperpnea (r(2) = 0.49). At maximum ventilation, diaphragm
      radius of curvature at end inspiration increased in COPD (P = 0.04) but not
      controls; diaphragm radius of curvature at end inspiration and ln(Eff(di)) were
      negatively correlated (P = 0.01). Thus in COPD with modest airflow obstruction,
      Eff(di) did not increase normally with hyperpnea due to a constant L(di ee) and
      inspiratory flattening of the diaphragm.

PMID- 22995392
TI  - Intrinsic aerobic capacity correlates with greater inherent mitochondrial
      oxidative and H2O2 emission capacities without major shifts in myosin heavy chain
      isoform.
AB  - Exercise capacity and performance strongly associate with metabolic and
      biophysical characteristics of skeletal muscle, factors that also relate to
      overall disease risk. Despite its importance, the exact mechanistic features that
      connect aerobic metabolism with health status are unknown. To explore this, we
      applied artificial selection of rats for intrinsic (i.e., untrained) aerobic
      treadmill running to generate strains of low- and high-capacity runners (LCR and
      HCR, respectively), subsequently shown to diverge for disease risk. Concurrent
      breeding of LCR and HCR per generation allows the lines to serve as reciprocal
      controls for unknown environmental changes. Here we provide the first direct
      evidence in mitochondria isolated from skeletal muscle that intrinsic
      mitochondrial capacity is higher in HCR rats. Maximal phosphorylating respiration
      was ~40% greater in HCR mitochondria, independent of substrate and without
      altered proton leak or major changes in protein levels or muscle fiber type,
      consistent with altered control of phosphorylating respiration. Unexpectedly,
      H(2)O(2) emission was ~20% higher in HCR mitochondria, due to greater reduction
      of more harmful reactive oxygen species to H(2)O(2); indeed, oxidative
      modification of mitochondrial proteins was lower. When the higher mitochondrial
      yield was considered, phosphorylating respiration and H(2)O(2) emission were 70
      80% greater in HCR muscle. Greater capacity of HCR muscle for work and H(2)O(2)
      signaling may result in enhanced and more immediate cellular repair, possibly
      explaining lowered disease risks.

PMID- 22995394
TI  - Functional assessments of the knee joint biomechanics by using pendulum test in
      adults with Down syndrome.
AB  - In this study, we assessed kinematics and viscoelastic features of knee joint in
      adults with Down syndrome (DS) by means of the Wartenberg pendulum test. This
      test allows the measuring of the kinematics of the knee joint during passive
      pendular motion of leg under the influence of gravity. In addition, by a
      combination of kinematic and anthropometric data, pendulum test provides
      estimates of joint viscoelastic properties by computing damping and stiffness
      coefficients. To monitor the occurrences of muscle activation, the surface
      electromyogram (EMG) of muscle rectus femoris was recorded. The experimental
      protocol was performed in a group of 10 adults with DS compared with 10 control
      adults without DS. Joint motion amplitude, velocity, and acceleration of the leg
      during the first knee flexion significantly decreased in persons with DS with
      respect to those without DS. This behavior was associated with the activation of
      rectus femoris in subjects with DS that resulted in increasing of joint
      resistance shortly after the onset of the first leg flexion. The EMG bursts
      mostly occurred between 50 and 150 ms from the leg flexion onset. During the
      remaining cycles of pendular motion, persons with DS exhibited passive leg
      oscillations with low tonic EMG activity and reduced damping coefficient compared
      with control subjects. These results suggest that adults with DS might perform
      preprogrammed contractions to increase joint resistance and compensate for
      inherent joint instability occurring for quick and unpredictable perturbations.
      The reduction of damping coefficients observed during passive oscillations could
      be a predictor of muscle hypotonia.

PMID- 22995396
TI  - Validity of hip-mounted uniaxial accelerometry with heart-rate monitoring vs.
      triaxial accelerometry in the assessment of free-living energy expenditure in
      young children: the IDEFICS Validation Study.
AB  - One of the aims of Identification and Prevention of Dietary- and Lifestyle
      Induced Health Effects in Children and Infants (IDEFICS) validation study is to
      validate field measures of physical activity (PA) and energy expenditure (EE) in
      young children. This study compared the validity of uniaxial accelerometry with
      heart-rate (HR) monitoring vs. triaxial accelerometry against doubly labeled
      water (DLW) criterion method for assessment of free-living EE in young children.
      Forty-nine European children (25 female, 24 male) aged 4-10 yr (mean age: 6.9 +/-
      1.5 yr) were assessed by uniaxial ActiTrainer with HR, uniaxial 3DNX, and
      triaxial 3DNX accelerometry. Total energy expenditure (TEE) was estimated using
      DLW over a 1-wk period. The longitudinal axis of both devices and triaxial 3DNX
      counts per minute (CPM) were significantly (P < 0.05) associated with physical
      activity level (PAL; r = 0.51 ActiTrainer, r = 0.49 uniaxial-3DNX, and r = 0.42
      triaxial Sigma3DNX). Eight-six percent of the variance in TEE could be predicted
      by a model combining body mass (partial r(2) = 71%; P < 0.05), CPM-ActiTrainer
      (partial r(2) = 11%; P < 0.05), and difference between HR at moderate and
      sedentary activities (ModHR - SedHR) (partial r(2) = 4%; P < 0.05). The SE of TEE
      estimate for ActiTrainer and 3DNX models ranged from 0.44 to 0.74 MJ/days or ~7
      11% of the average TEE. The SE of activity-induced energy expenditure (AEE) model
      estimates ranged from 0.38 to 0.57 MJ/day or 24-26% of the average AEE. It is
      concluded that the comparative validity of hip-mounted uniaxial and triaxial
      accelerometers for assessing PA and EE is similar.

PMID- 22995395
TI  - Bone metabolism and nutritional status during 30-day head-down-tilt bed rest.
AB  - Bed rest studies provide an important tool for modeling physiological changes
      that occur during spaceflight. Markers of bone metabolism and nutritional status
      were evaluated in 12 subjects (8 men, 4 women; ages 25-49 yr) who participated in
      a 30-day -6 degrees  head-down-tilt diet-controlled bed rest study. Blood and
      urine samples were collected twice before, once a week during, and twice after
      bed rest. Data were analyzed using a mixed-effects linear regression with a
      priori contrasts comparing all days to the second week of the pre-bed rest
      acclimation period. During bed rest, all urinary markers of bone resorption
      increased ~20% (P < 0.001), and serum parathyroid hormone decreased ~25% (P <
      0.001). Unlike longer (>60 days) bed rest studies, neither markers of oxidative
      damage nor iron status indexes changed over the 30 days of bed rest. Urinary
      oxalate excretion decreased ~20% during bed rest (P < 0.001) and correlated
      inversely with urinary calcium (R = -0.18, P < 0.02). These data provide a broad
      overview of the biochemistry associated with short-duration bed rest studies and
      provide an impetus for using shorter studies to save time and costs wherever
      possible. For some effects related to bone biochemistry, short-duration bed rest
      will fulfill the scientific requirements to simulate spaceflight, but other
      effects (antioxidants/oxidative damage, iron status) do not manifest until
      subjects are in bed longer, in which case longer studies or other analogs may be
      needed. Regardless, maximizing research funding and opportunities will be
      critical to enable the next steps in space exploration.

PMID- 22995397
TI  - Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone
      methylation of liver IGF-1 might cause skeletal growth retardation.
AB  - Several epidemiological investigations, including previous work by our
      laboratory, indicate that maternal caffeine consumption is associated with
      intrauterine growth retardation and impaired fetal length growth. Skeletal
      development is critical for length growth. In the present study, our goals were
      to determine the effects of prenatal caffeine exposures on fetal skeletal growth
      and to investigate the mechanisms associated with such effects. Pregnant Wistar
      rats were injected intragastrically with 120mg/kg of caffeine intragastrically
      each day from gestational days 11-20. Maternal prenatal caffeine exposure was
      associated with decreased fetal femur lengths and inhibited of synthesis of
      extracellular matrices in fetal growth plates Moreover, caffeine exposure
      significantly increased the levels of fetal blood corticosterone and decreased
      IGF-1mRNA expression levels in the liver and growth plate. The expression levels
      of IGF-1 signaling pathway components (IGF-1R, IRS-1, AKT1/2 and Col2A1) were
      also reduced. In addition, the results of chromatin immunoprecipitation assays
      indicated that caffeine exposure down-regulated histone methylation of fetal IGF
      1 in the liver. These results suggest that prenatal caffeine exposure may inhibit
      fetal skeletal growth through a mechanism that is associated with increased fetal
      exposure to maternal glucocorticoids and results in lower IGF-1 signaling pathway
      activity. Taken together, these results raise important concerns regarding the
      skeletal growth toxicity of caffeine and potentially indicate the intrauterine
      origins of adult osteoporosis and osteoarthritis.

PMID- 22995399
TI  - Non-elective percutaneous nephrostomy (PCN) service in a tertiary uroradiology
      centre: can radiologists and urologists agree on timing?
AB  - AIM: To assess agreement between uroradiologists and urologists with regards to
      the timing of non-elective percutaneous nephrostomy (PCN) catheter insertion, and
      whether any delay produced unacceptable complications. MATERIALS AND METHODS:
      Standardized data collection forms detailing patient demographics, indications
      for PCN catheter insertion, blood results, procedural details, and immediate
      complications were completed by uroradiologists. At the time of referral,
      patients were stratified by both radiologists and urologists into three groups as
      follows: group 1 = PCN within 6 h; group 2 = PCN between 6 and 24 h; and group 3
      = PCN between 24 and 48 h. RESULTS: One hundred and eighteen non-elective PCN
      catheter insertions were performed over 2 years. Radiologists stratified 12
      patients (10.2%) into group 1, 65 (55.1%) patients into group 2, and 41 (34.7%)
      patients into group 3. Urologists stratified 14 (11.9%) patients into group 1, 68
      (57.6%) patients into group 2, and 36 (30.5%) patients into group 3. There was
      good agreement between radiologist and urologists (kappa = 0.865) on
      stratification in all but nine (7.6%) cases. Ninety-four point one percent of PCN
      catheters were inserted within the timeframe stratified by radiologists and
      urologists, or sooner. Sepsis was associated with a shortened timeframe. Elevated
      international normalized ratio (INR; >1.5) resulted in an increased timeframe. A
      major complication rate of 3% is within recommended limits. Fourteen percent of
      PCN catheter insertions were inserted outside normal working hours. Urgency
      stratification has decreased the number of cases performed out of hours.
      CONCLUSION: Radiologists and urologists had good agreement on stratification with
      an acceptable major complication rate of 3%.

PMID- 22995400
TI  - Confidence in one's social beliefs: implications for belief justification.
AB  - Philosophers commonly define knowledge as justified true beliefs. A heated debate
      exists, however, about what makes a belief justified. In this article, we examine
      the question of belief justification from a psychological perspective, focusing
      on the subjective confidence in a belief that the person has just formed.
      Participants decided whether to accept or reject a proposition depicting a social
      belief, and indicated their confidence in their choice. The task was repeated six
      times, and choice latency was measured. The results were analyzed within a Self
      Consistency Model (SCM) of subjective confidence. According to SCM, the decision
      to accept or reject a proposition is based on the on-line sampling of
      representations from a pool of representations associated with the proposition.
      Respondents behave like intuitive statisticians who infer the central tendency of
      a population based on a small sample. Confidence depends on the consistency with
      which the belief was supported across the sampled representations, and reflects
      the likelihood that a new sample will yield the same decision. The results
      supported the assumption of a commonly shared population of representations
      associated with each proposition. Based on this assumption, analyses of within
      person consistency and cross-person consensus provided support for the model. As
      expected, choices that deviated from the person's own modal judgment or from the
      consensually held judgment took relatively longer to form and were associated
      with relatively lower confidence, presumably because they were based on non
      representative samples. The results were discussed in relation to major
      epistemological theories--foundationalism, coherentism and reliabilism.

PMID- 22995398
TI  - Effect of divalent metals on the neuronal proteasomal system, prion protein
      ubiquitination and aggregation.
AB  - The role of normal cellular prion protein (PrP) remains to be fully elucidated;
      however, the protein is crucial for the infection and progression of prion
      diseases. Recent evidence indicates that PrP is a metalloprotein since the
      octapeptide repeat sequences in the protein have high affinity for various
      divalent cations and the binding sites appear to play a role in the pathogenesis
      of prion diseases. In our present study, we tested several divalent metals
      including manganese and cadmium and determined their effects on protein
      degradation and protein aggregation in mouse neuronal cells expressing PrP.
      Cadmium was more neurotoxic than manganese following 24h exposure. Manganese did
      not show any significant effect on the inhibition of proteasomal activity or
      formation of high molecular weight ubiquitinated PrPs. Interestingly, treatment
      with cadmium profoundly inhibited proteasomal activity, which resulted in greatly
      increased formation of high molecular weight ubiquitinated PrPs.
      Immunohistochemical analysis also revealed a dramatic increase in formation of
      oligomers after cadmium treatment. Cadmium also increased the formation of
      ubiquitinated PrP, but it did not lead to the formation of proteinase-K resistant
      PrP. Collectively, our results show that a divalent metal, cadmium affects
      proteasomal function and PrP aggregation, which promote neurotoxicity.

PMID- 22995401
TI  - Protective effect of lactofermented red beetroot juice against aberrant crypt
      foci formation, genotoxicity of fecal water and oxidative stress induced by 2
      amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in rats model.
AB  - The aim of the study was to investigate the effects of beetroot juice fermented
      by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen
      induction of aberrant crypt foci (ACF) in rat colon. 2-Amino-1-methyl-6
      phenylimidazo[4,5-b] pyridine (PhIP) was used as carcinogen, which was
      administrated intragastrically at a dose of 10 MUg/day, every day of the
      experiment. Additionally, we investigated the cytotoxicity and genotoxicity of
      fecal water from experimental animals in the Caco-2 cell line, evaluated by MTT
      test and the comet assay, respectively, as well as by the count of bacteria
      adhered to colon epithelium assessed by fluorescence in situ hybridization.
      Oxidative stress in rats was expressed by measuring serum antioxidant status and
      the level of malondialdehyde in the kidneys and liver. The experimental rats were
      divided into four groups based on diet type: basal diet, basal diet supplemented
      with FBJ, basal diet and PhIP treatment, and basal diet supplemented with FBJ and
      PhIP treatment. FBJ significantly reduced the number of ACF in PhIP-treated rats
      (from 59 +/- 18 to 26 +/- 4). Moreover, the number of extensive aberrations (more
      than 4 crypts in a focus) decreased from 52 +/- 18 to 18 +/- 4. Fecal water
      obtained from rats fed with a PhIP-containing diet induced pronounced cytotoxic
      and genotoxic effects in Caco-2 cells, but FBJ supplementation of the diet
      abolished these effects. In groups fed dietary PhP and FBJ the latter was found
      to increase the antioxidant status of serum from 40% to 66% depending on the
      fraction. Reduced concentration of malondialdehyde was found only in the kidneys
      of rats fed with PhIP and FBJ. FBJ present in the diet of rats causes a reduction
      of MDA in the kidneys from 118.7 nmol/g tissue to 100 nmol/g tissue. The presence
      of FBJ in the diet of rats significantly increased the count of bacteria,
      including Lactobacillus/Enterococcus and Bacteroides-Prevotella group adhered to
      colonic epithelium. In conclusion, supplementation of the diet with
      lactofermented beetroot juice may provide protection against precancerous
      aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal
      water and improve the oxidative status of the organism.

PMID- 22995402
TI  - AMP-activated protein kinase stimulates myostatin expression in C2C12 cells.
AB  - AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism in
      skeletal muscle; AMPK induces muscle protein degradation but the underlying
      mechanisms are unclear. Myostatin is a powerful negative regulator of skeletal
      muscle mass and growth in mammalian species. We hypothesized that AMPK stimulates
      myostatin expression, which provides an explanation for the negative role of AMPK
      in muscle growth. The objective of this study is to demonstrate that AMPK
      stimulates myostatin expression using C2C12 cells as a model. Activation of AMPK
      by 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) dramatically
      increased the mRNA expression and protein content of myostatin in C2C12 myotubes,
      and to a lesser degree in myoblasts. Metformin, another AMPK activator, also
      stimulated myostatin expression at low concentrations. In addition, ectopic
      expression of AMPK wild-type alpha subunit (enhancing AMPK activity) and AMPK
      K45R mutant (knockdown AMPK activity) enhanced and reduced myostatin expression,
      respectively. These results indicate that AMPK stimulates myostatin expression in
      C2C12 cells, providing an explanation for the negative effect of AMPK on muscle
      growth.

PMID- 22995404
TI  - Effect of ProNectin F derivatives on cell attachment and proliferation.
AB  - ProNectin F (PnF) was chemically modified by introducing some functional groups
      to prepare various derivatives of primary amino (PnF-N1), tertiary amino (PnF
      N3), quaternary ammonium (PnF-N4), carboxyl (PnF-COOH) and sulfonyl groups (PnF
      SO3H). When C3H10T1/2 cells were cultured on non-treated dishes coated with the
      derivatives, the number of mesenchymal cells attached to the culture dishes
      increased for the coating with PnF-COOH and PnF-SO3H, even at their low
      adsorption amount. The cytotoxicity was high for the coating of PnF-N1 and PnF-N4
      compared with that of the PnF-N3, PnF-COOH and PnF-SO3H. The treatment with
      integrin alpha5 and alphaV antibodies suppressed the cell attachment to the
      dishes coated with PnF-COOH and PnF-SO3H. The phosphorylation of extracellular
      signal-regulated kinase (ERK) was upregulated for cells attached to the dishes
      coated with PnF-COOH and PnF-SO3H, indicating their enhanced proliferation. It is
      concluded that the chemical derivatization of PnF enhanced the ability of cell
      attachment and proliferation.

PMID- 22995403
TI  - Biodegradable nanocomposite hydrogel structures with enhanced mechanical
      properties prepared by photo-crosslinking solutions of poly(trimethylene
      carbonate)-poly(ethylene glycol)-poly(trimethylene carbonate) macromonomers and
      nanoclay particles.
AB  - Soft hydrogels with elasticity modulus values lower than 100kPa that are tough
      and biodegradable are of great interest in medicine and in tissue engineering
      applications. We have developed a series of soft hydrogel structures from
      different methacrylate-functionalized triblock copolymers of poly(ethylene
      glycol) (PEG) with poly(trimethylene carbonate) (PTMC) by photo-crosslinking
      aqueous solutions of the macromonomers in 2.5 and 5wt.% colloidal dispersions of
      clay nanoparticles (Laponite XLG). The length of the PTMC blocks of the
      macromonomers and the clay content determined the physicomechanical properties of
      the obtained hydrogels. While an increase in the PTMC block length in the
      macromonomers from 0.2 to 5kg/mol resulted in a decrease in the gel content, the
      addition of 5wt.% Laponite nanoclay to the crosslinking solution lead to very
      high gel contents of the hydrogels of more than 95%. The effect of PTMC block
      length on the mechanical properties of the hydrogels was not as pronounced, and
      soft gels with a compressive modulus of less than 15kPa and toughness values of
      25kJm(-3) were obtained. However, the addition of 5wt.% Laponite nanoclay to the
      formulations considerably increased the compressive modulus and resilience of the
      hydrogels; swollen nanocomposite networks with compressive modulus and toughness
      values of up to 67kPa and 200kJm(-3), respectively, could then be obtained. The
      prepared hydrogels were shown to be enzymatically degradable by cholesterol
      esterase and by the action of macrophages. With an increase in PTMC block length
      in the hydrogels, the rates of mass loss increased, while the incorporated
      Laponite nanoclay suppressed degradation. Nanocomposite hydrogel structures with
      a designed gyroid pore network architecture were prepared by stereolithography.
      Furthermore, in the swollen state the porous gyroid structures were mechanically
      stable and the pore network remained fully open and interconnected.

PMID- 22995405
TI  - Long-term three-dimensional neural tissue cultures in functionalized self
      assembling peptide hydrogels, matrigel and collagen I.
AB  - Designer peptides with self-assembling properties form nanofibers which are
      further organized to form a hydrogel consisting of up to 99.5% water. We present
      here the encapsulation of neural stem cells into peptide nanofiber hydrogel
      scaffolds. This results in three-dimensional (3-D) neural tissue cultures in
      which neural stem cells differentiate into progenitor neural cells, neurons,
      astrocytes and oligodendrocytes when cultured in serum-free medium. Cell survival
      studies showed that neural cells in peptide hydrogels thrive for at least 5
      months. In contrast, neural stem cells encapsulated in Collagen I were poorly
      differentiated and did not migrate significantly, thus forming clusters. We show
      that for culture periods of 1-2 weeks, neural stem cells proliferate and
      differentiate better in Matrigel. However, in long-term studies, the population
      of cells in Matrigel decreases whereas better cell survival rates are observed in
      neural tissue cultures in peptide hydrogels. Peptide functionalization with cell
      adhesion and cell differentiation motifs show superior cell survival and
      differentiation properties compared to those observed upon culturing neural cells
      in non-modified peptide hydrogels. These designed 3-D engineered tissue culturing
      systems have a potential use as tissue surrogates for tissue regeneration. The
      well-defined chemical and physical properties of the peptide nanofiber hydrogels
      and the use of serum-free medium allow for more realistic biological studies of
      neural cells in a biomimetic 3-D environment.

PMID- 22995406
TI  - Effect of gastric environment on Helicobacter pylori adhesion to a mucoadhesive
      polymer.
AB  - Helicobacter pylori infection has been associated with several gastric diseases.
      This bacterium colonizes the gastric mucosa of half of the world's population,
      and available treatments are unsuccessful in practically one in every five
      patients. Mucoadhesive polymers, such as chitosan, are being investigated as
      gastric drug delivery systems. However, since chitosan is also known for its
      antimicrobial properties, this work aims to evaluate H. pylori interactions with
      chitosan under simulated gastric environments, namely using various pHs (2.6, 4
      and 6), pepsin and urea. To enable the visualization of adherent bacteria,
      ultrathin chitosan films were produced by spin-coating on gold/glass surfaces,
      cross-linked with genipin and characterized by Fourier transform infrared
      reflection absorption spectroscopy, ellipsometry and electrokinetic analysis.
      Films with homogeneous thickness of 11.7+/-0.6 nm were produced, and were stable
      and protonated at all the pHs used. Furthermore, they adsorbed pepsin in all
      these pHs, in contrast to urea, of which a small adsorption was only observed at
      pH 6. H. pylori binding to chitosan was higher at pH2.6 although most of adherent
      bacteria were dead. The presence of pepsin decreased bacterial adhesion, but
      increased its viability while in a more stressed morphology (coccoid form). The
      presence of urea did not affect the amount, morphology or viability of chitosan
      adherent bacteria. In suspension, the decrease in pH changed H. pylori zeta
      potential from negative to positive. Moreover, bacteria were only culturable when
      incubated in pH 6 with and without urea (without pepsin). This work demonstrates
      that chitosan has the capacity to bind and kill H. pylori in a range of pHs
      independently of urea. This opens new perspectives for the application of
      chitosan-based materials to the elimination of H. pylori gastric colonization,
      though pepsin might appear to be an obstacle.

PMID- 22995407
TI  - A high poly(ethylene glycol) density on graphene nanomaterials reduces the
      detachment of lipid-poly(ethylene glycol) and macrophage uptake.
AB  - Amphiphilic lipid-poly(ethylene glycol) (LPEG) is widely used for the noncovalent
      functionalization of graphene nanomaterials (GNMs) to improve their dispersion in
      aqueous solutions for biomedical applications. However, not much is known about
      the detachment of LPEGs from GNMs and macrophage uptake of dispersed GNMs in
      relation to the alkyl chain coverage, the PEG coverage, and the linker group in
      LPEGs. In this study we examined these relationships using single walled carbon
      nanohorns (SWCNHs). The high coverage of PEG rather than that of alkyl chains was
      dominant in suppressing the detachment of LPEGs from SWCNHs in protein-containing
      physiological solution. Correspondingly, the quantity of LPEG-covered SWCNHs
      (LPEG-SWCNHs) taken up by macrophages decreased at a high PEG coverage. Our study
      also demonstrated an effect of the ionic group in LPEG on SWCNH uptake into
      macrophages. A phosphate anionic group in the LPEG induced lower alkyl chain
      coverage and easy detachment of the LPEG, however, the negative surface charge of
      LPEG-SWCNHs reduced the uptake of SWCNHs by macrophages.

PMID- 22995408
TI  - Adipose stem cell-derived osteoblasts sustain the functionality of endothelial
      progenitors from the mononuclear fraction of umbilical cord blood.
AB  - Vascularization is the most pressing issue in tissue engineering (TE) since
      ensuring that engineered constructs are adequately perfused after in vivo
      transplantation is essential for the construct's survival. The combination of
      endothelial cells with current TE strategies seems the most promising approach
      but doubts persist as to which type of endothelial cells to use. Umbilical cord
      blood (UCB) cells have been suggested as a possible source of endothelial
      progenitors. Osteoblasts obtained from human adipose-derived stem cells (hASCs)
      were co-cultured with the mononuclear fraction of human UCB for 7 and 21 days on
      carrageenan membranes. The expression of vWF and CD31, and the DiI-AcLDL uptake
      ability allowed detection of the presence of endothelial and monocytic lineages
      cells in the co-culture for all culture times. In addition, the molecular
      expression of CD31 and VE-cadherin increased after 21 days of co-culture. The
      functionality of the system was assessed after transplantation in nude mice.
      Although an inflammatory response developed, blood vessels with cells positive
      for human CD31 were detected around the membranes. Furthermore, the number of
      blood vessels in the vicinity of the implants increased when cells from the
      mononuclear fraction of UCB were present in the transplants compared to
      transplants with only hASC-derived osteoblasts. These results show how
      endothelial progenitors present in the mononuclear fraction of UCB can be
      sustained by hASC-derived osteoblast co-culture and contribute to angiogenesis
      even in an in vivo setting of inflammatory response.

PMID- 22995409
TI  - Cancer stem cells from a rare form of glioblastoma multiforme involving the
      neurogenic ventricular wall.
AB  - BACKGROUND: The cancer stem cell (CSC) hypothesis posits that deregulated neural
      stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme
      (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs
      reside in subventricular and hippocampal regions. We attempted to characterize
      CSCs from a rare form of glioblastoma multiforme involving the neurogenic
      ventricular wall. METHODS: We described isolating CSCs from a GBM involving the
      lateral ventricles and characterized these cells with in vitro molecular
      biomarker profiling, cellular behavior, ex vivo and in vivo techniques. RESULTS:
      The patient's MRI revealed a heterogeneous mass with associated edema, involving
      the left subventricular zone. Histological examination of the tumor established
      it as being a high-grade glial neoplasm, characterized by polygonal and fusiform
      cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli,
      frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia.
      Recurrence of the tumor occurred shortly after the surgical resection. CD133
      positive cells, isolated from the tumor, expressed stem cell markers including
      nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin,
      Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included
      Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of
      unique cancer-related transcripts in these CD133-positive cells, such as caveolin
      1 and -2, do not appear to have been previously reported in the literature. Ex
      vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like
      tumor cells. The CD133-positive cells also induced tumor formation when they were
      stereotactically transplanted into the brains of the immune-deficient NOD/SCID
      mice. CONCLUSIONS: This brain tumor involving the neurogenic lateral ventricular
      wall was comprised of tumor-forming, CD133-positive cancer stem cells, which are
      likely the driving force for the rapid recurrence of the tumor in the patient.

PMID- 22995410
TI  - [Spanish medical students and Family Medicine. Data from the two phases of a
      national questionnaire].
AB  - OBJECTIVE: To examine the perceptions and expectations about Family Practice (FP)
      and Primary Care (PC) in 1st, 3rd and 5th year students in medical schools.
      DESIGN: An observational study in two cross sections with intervals of two years.
      LOCATION: Spanish Medical Schools. PARTICIPANTS: 1st, 3rd and 5th year students
      of 22 schools (1st phase) and 15 (second phase). PRIMARY MEASUREMENTS: Self
      report questionnaires completed during the first quarter of the 2009-2010 and
      2011-2012 academic years. It had 70 items in three blocks: perceptions of FP (19
      items), training in FP (26 items), expectations and preferences (25 items), plus
      13 specific items for 3rd and 5th year students. Most of the items were answered
      in a 6 point Likert scale. RESULTS: A total of 5299 responses in phase I, and
      3869 in phase II were received. Students perceive FP and PC as essential areas of
      the health system and professional practice, but with little scientific and
      technical appeal. The large majortiy, 87%, consider training in FP necessary and
      compulsory, and it should start in third year. They prefer hospital medical
      specialities (88-89%), followed by surgical and paediatrics. FP is preferred by
      the 37-39%. Only between 24% and 28% of students have a clear preference for a
      specialty when they start medical studies. CONCLUSIONS: FP and PC are key areas
      and should be part of the curriculum, but are perceived to be of low scientific
      appeal.

PMID- 22995411
TI  - Concordance of CKD stages in estimation by the CKD-EPI equation and estimation by
      the MDRD equation in the Japanese general population: the Iwate KENCO Study.

PMID- 22995412
TI  - Late acquired double lumina in a sirolimus-eluting stent recanalized chronic
      total occlusion lesion: angiographic and optical coherence tomographic findings.

PMID- 22995413
TI  - Right atrium giant blood cyst in a young female with acute pericarditis,
      complicated with fatal cardiac tamponade.

PMID- 22995414
TI  - Recreational and occupational physical activities as risk factors for
      cardiovascular disease.

PMID- 22995415
TI  - Early and long-term outlook of percutaneous coronary intervention for bifurcation
      lesions in young patients.
AB  - BACKGROUND: Coronary artery disease is most common in older patients, but may
      occur in younger subjects. The outlook of young patients after percutaneous
      coronary intervention (PCI) of challenging lesion subsets such as coronary
      bifurcations, is not established. We thus aimed to appraise the early and long
      term results of PCI for bifurcations in young patients. METHODS: A multicenter,
      retrospective study was conducted enrolling consecutive patients undergoing
      bifurcation PCI between 2002 and 2006 in 22 Italian centers. Patients were
      divided in 2 groups: age <= 45 years, and age > 45 years. The primary end-point
      was long-term rate of major adverse cardiac events (MACE). RESULTS: 4,314
      patients were included: 195 (4.5%) in the younger group, and 4119 (95.5%) in the
      older group. 30-day outcomes did not show significant differences in MACE rates,
      with 1.0% in the <= 45 years group and 2.1% in the >45 years group (p=0.439),
      with death in 0.5% and 1.2% (p=0.388). At long-term follow-up (24.4 +/- 15.1
      months), younger patients showed similar rates of MACE, (12.8% vs. 16.6%,
      p=0.161), myocardial infarction (3.1% vs. 3.7%, p=0.633), target lesion
      revascularization (11.3% vs. 12.5%, p=0.627), or stent thrombosis (1.5% vs. 2.8%,
      p=0.294), despite an increased risk of death in older patients (1.0% vs. 5.0%,
      p=0.012). Even at extensive multivariable analysis, younger patients still faced
      a similar risk of MACE (HR=0.78 [0.48-1.27], p=0.318). CONCLUSIONS: Despite their
      low age, young patients undergoing PCI for bifurcation face a significant risk of
      early and late non-fatal adverse events. Thus, they should not be denied careful
      medical management and follow-up.

PMID- 22995416
TI  - Ivabradine is BEAUTIFUL in concurrent acute coronary syndrome and stroke.

PMID- 22995417
TI  - Percutaneous pulmonary valve replacement after different duration of free
      pulmonary regurgitation in a porcine model: effects on the right ventricle.
AB  - BACKGROUND: Free pulmonary regurgitation (PR) after surgical correction of
      Tetralogy of Fallot (ToF) with transannular patching can lead to irreversible
      right ventricular (RV) failure. However, the optimal timing of valve replacement
      is still debated. METHODS AND RESULTS: Thirty six pigs were included in the
      study. Twenty one pigs had a bare metal stent placed in the pulmonary annulus
      inducing free PR and 9 animals served as control. Six animals died prematurely
      due to procedural complications. The 21 animals were divided into 3 groups with
      differential duration of PR (1, 2, 3 months, respectively) after which PPVR was
      performed. After 1 month with competent valve the animals were euthanized.
      Cardiac magnetic resonance (CMR) and right heart catheterization were performed
      serially. Free PR led to severe dilation of the RV in all three groups compared
      to matched controls (p<0.001). Final RV volume after one month with competent
      pulmonary valve was modeled. Increase in RV volume from baseline to valve
      replacement (DeltaRV) was the only predictor of RV recovery (p<0.001) and
      increases in DeltaRV beyond 120 mL/m2 were predictive of very low probability of
      recovery. A total of 5 animals did not recover. CONCLUSIONS: Recovery of right
      ventricular function after free PR by treatment with PPVR was successful in the
      majority of animals. Increases in RV volume during PR were the only predictor of
      non-recovery after PPVR and duration of PR did not in itself predict treatment
      success.

PMID- 22995419
TI  - PCOS must be kept in mind in young females especially those without traditional
      risk factors but suffered from coronary events.

PMID- 22995418
TI  - Adverse effects of cilostazol on left ventricular function in a patient with a
      sigmoid shaped interventricular septum.

PMID- 22995420
TI  - John Hunter (1728-93) and the earliest description of bicuspid aortic valves.

PMID- 22995421
TI  - Lightning burn--review and case report.

PMID- 22995422
TI  - A reason to be careful about frostbite injury: carbon dioxide fire extinguisher
      failure.

PMID- 22995423
TI  - Administration of poly(ADP-ribose) polymerase inhibitor into bronchial artery
      attenuates pulmonary pathophysiology after smoke inhalation and burn in an ovine
      model.
AB  - Poly(ADP-ribose) polymerase (PARP) is well known to be an enzyme that repairs
      damaged DNA and also induces cell death when overactivated. It has been reported
      that PARP plays a significant role in burn and smoke inhalation injury, and the
      pathophysiology is thought to be localized in the airway during early stages of
      activation. Therefore, we hypothesized that local inhibition of PARP in the
      airway by direct delivery of low dose PJ-34 [poly(ADP-ribose) polymerase
      inhibitor] into the bronchial artery would attenuate burn and smoke-induced acute
      lung injury. The bronchial artery in sheep was cannulated in preparation for
      surgery. After a 5-7 day recovery period, sheep were administered a burn and
      inhalation injury. Adult female sheep (n=19) were divided into four groups
      following the injury: (1) PJ-34 group A: 1h post-injury, PJ-34 (0.003mg/kg/h,
      2mL/h) was continuously injected into the bronchial artery, n=5; (2) PJ-34 group
      B: 1h post-injury, PJ-34 (0.03mg/kg/h, 2mL/h) was continuously injected into
      bronchial artery, n=4; (3) CONTROL GROUP: 1h post-injury, an equivalent amount of
      saline was injected into the bronchial artery, n=5; (4) Sham group: no injury, no
      treatment, same operation and anesthesia, n=5. After injury, all animals were
      placed on a ventilator and fluid resuscitated equally. Pulmonary function as
      evaluated by measurement of blood gas analysis, pulmonary mechanics, and
      pulmonary transvascular fluid flux was severely deteriorated in the control
      group. However, the above changes were markedly attenuated by PJ-34 infusion into
      the bronchial artery (P/F ratio at 24h: PJ-34 group A 398+/-40*, PJ-34 group B
      438+/-41*??, Control 365+/-58*, Sham 547+/-47; * vs. sham [p<0.05], ? vs. control
      [p<0.05], ? vs. PJ-34 group A [p<0.05]). Our data strongly suggest that local
      airway production of poly(ADP-ribose) polymerase contributes to pulmonary
      dysfunction following smoke inhalation and burn.

PMID- 22995424
TI  - Neonatal burns in Lagos, South-Western Nigeria: Epidemiology and outcome of
      management.
AB  - BACKGROUND: Burns in the neonate are rare and result mostly from iatrogenic
      sources in developed countries. The socioeconomic settings of developing
      countries are different from those in the developed countries. A review of the
      epidemiology and management of burns in the neonates in Lagos, Nigeria is
      presented. METHODS: The case notes of burns in patients less than 29 days-old
      from 2004 to 2008 in 4 tertiary health institutions in Lagos were retrieved from
      the Medical Records Department; necessary data were extracted and analyzed.
      RESULTS: There were 21 neonates with burns within the study period. The incidence
      of neonatal burns ranged between 0.5 and 2.5%/year. The mean age was 16.38 +/-
      1.84 days and the mean BSA of 26.00 +/- 5.53%. The etiology of burns was thermal
      in 19(90.5%) and chemical in 2(9.5%). Hypokalemia was common at early stages of
      their treatment. Burns were sustained at home in 90.5% of the cases. The
      mortality rate was 43.5%. Inhalation and thermal injuries were associated with
      most of the deaths. CONCLUSION: Domestic incidents from flames are the commonest
      causes of neonatal burns in the study environment. These are associated with
      prolonged morbidity and high mortality rate. Health education, highlighting
      methods of prevention should be undertaken in the community. Well equipped burn
      centers should be established to treat burns in all age groups.

PMID- 22995425
TI  - Lowering the pivot point of sural neurofasciocutaneous flaps to reconstruct deep
      electrical burn wounds in the distal foot.
AB  - Due to the thinness of the skin and soft tissues in the foot, tendons and bones
      tend to become exposed and necrotic after injury; therefore, it is difficult to
      reconstruct foot injuries, especially distally. Reconstruction with free skin
      flaps is highly risky as it demands technologies and equipment, while patients
      suffer greatly from the use of cross-leg skin flaps. Sural neurofasciocutaneous
      flaps are often used for reconstruction of wounds in the lower leg, malleolus,
      and the proximal end of the foot but are not feasible for wound repair in the
      distal foot; this is because, with the pivot point of 5-7 cm above the tip of the
      lateral malleolus, the flaps are not able to cover defects in the distal foot. In
      this study, we used a sural neurofasciocutaneous flaps with a lowered pivot point
      for reconstruction of distal foot wounds caused by electrical burns. An
      ultrasound flow detector and Doppler flow imaging were used to detect the
      diameter, the perforating point and the blood flow of the lateral retromalleolar
      perforator. Twelve patients with the perforator diameter greater than 0.6 mm and
      the peak systolic flow more than 0.15 m/s were included. The pivot point of sural
      neurofasciocutaneous flaps was lowered to 0-3 cm above the tip of the lateral
      malleolus and the size of the flaps ranged from 6 cm * 5 cm to 12 cm * 18 cm.
      Eleven of the 12 flaps survived completely. One flap developed necrosis
      approximately 1cm at the far point but was managed successfully by daily
      dressing. We demonstrated that lowering the pivot point of sural
      neurofasciocutaneous flaps is feasible for reconstruction of distal foot injury
      with the advantages of reliable blood supply and easy operation. The use of
      Doppler flow imaging provides useful information for the design of the flaps.

PMID- 22995426
TI  - Chin projection creation in patients with facial and cervical burn scar
      contracture.
AB  - BACKGROUND: Loss of cervicomental angle is characteristic of severe facial and
      cervical burned patients due to scar contracture. This micrognathia-like
      deformity is also seen in patients following chin and neck reconstruction using
      skin expanded flaps. The aim of modern plastic surgery is to restore a harmonious
      and symmetrical facial appearance for burn survivors. METHODS: Six facial and
      cervical burned patients with micrognathia-like deformity after neck
      reconstructions were reported. Chin augmentation with Medpor implant through
      submental approach was performed in 4 patients and intraoral access in 2 cases to
      restore their favorable chin projections. Five of them received cervicomental
      contour reconstruction simultaneously. RESULTS: Patient follow-up ranged from 12
      to 18 months. No implants became exposed nor infected. All patients had
      satisfactory results. We reviewed our experience with the use of the Medpor
      implant in burn chin reconstruction including preoperative and postoperative
      radiograph analysis. CONCLUSIONS: With proper patient selection, pre-operative
      planning, and taking care of details during operation, augmentation genioplasty
      with Medpor implant offers a reliable, simple and satisfactory solution for
      improving micrognathia-like facial configurations in patients with scar
      contracture following severe burns.

PMID- 22995427
TI  - Evaluation of biofilm production and characterization of genes encoding type III
      secretion system among Pseudomonas aeruginosa isolated from burn patients.
AB  - Pseudomonas aeruginosa is one of the common pathogenic causes of serious
      infections in burn patients throughout the world. Type III secretion toxins are
      thought to promote the dissemination of P. aeruginosa from the site of infection,
      the bacterial evasion of the host immune response and inhibition of DNA synthesis
      leading to host cell death. A total of 96 isolates of P. aeruginosa were
      collected from wound infections of burn patients, from April to July 2010.
      Antimicrobial susceptibility of the isolates were determined by disk agar
      diffusion method. Polymerase chain reaction (PCR)-based method was used for
      targeting the genes encoding the type III secretion toxins. The quantitative
      determination of biofilm-forming capacity was determined by a colorimetric
      microtiter plate assay. All the isolates were resistant to cefixime and
      ceftriaxone. More than 90% of the isolates were resistant to amikacin,
      carbenicillin, cefepime, cefotaxime, cefpodoxime, gatifloxacin, gentamicin,
      piperacillin/tazobactam, ticarcillin and tobramycin. All the isolates carried the
      exoT gene, 95% carried exoY, 64.5% carried exoU and 29% carried the exoS gene.
      Most of the isolates (58%) carried both exoY and exoU genes while 24% showed the
      concomitant presence of exoS and exoY and 1% carried both exoS and exoU.
      Coexistence of exoS, exoY and exoU was seen in 4% of the isolates. Biofilm
      formation was seen in more than 96% of the isolates among which 47% were strong
      biofilm producers, 26% were moderate and 22.9% were weak biofilm formers. In
      conclusion, the findings of this study show that the genes, particularly the exoU
      gene, encoding the type III secretion toxins, are commonly disseminated among the
      P. aeruginosa strains isolated from burn patients.

PMID- 22995428
TI  - Granulocyte-macrophage colony-stimulating factor is a key mediator in
      experimental osteoarthritis pain and disease development.
AB  - INTRODUCTION: Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been
      shown to be important in the development of inflammatory models of rheumatoid
      arthritis and there is encouraging data that its blockade may have clinical
      relevance in patients with rheumatoid arthritis. The aims of the current study
      were to determine whether GM-CSF may also be important for disease and pain
      development in a model of osteoarthritis. METHODS: The role of GM-CSF was
      investigated using the collagenase-induced instability model of osteoarthritis.
      We studied both GM-CSF-/- mice and wild-type (C57BL/6) mice treated
      prophylactically or therapeutically with a monoclonal antibody to GM-CSF. Disease
      development (both early and late) was evaluated by histology and knee pain
      development was measured by assessment of weight distribution. RESULTS: In the
      absence of GM-CSF, there was less synovitis and matrix metalloproteinase-mediated
      neoepitope expression at week 2 post disease induction, and less cartilage damage
      at week 6. GM-CSF was absolutely required for pain development. Therapeutic
      neutralization of GM-CSF not only abolished the pain within 3 days but also led
      to significantly reduced cartilage damage. CONCLUSIONS: GM-CSF is key to the
      development of experimental osteoarthritis and its associated pain. Importantly,
      GM-CSF neutralization by a therapeutic monoclonal antibody-based protocol rapidly
      and completely abolished existing arthritic pain and suppressed the degree of
      arthritis development. Our results suggest that it would be worth exploring the
      importance of GM-CSF for pain and disease in other osteoarthritis models and
      perhaps clinically for this form of arthritis.

PMID- 22995429
TI  - High-resolution melting: applications in genetic disorders.
AB  - High-resolution melting (HRM) analysis is a feasible and powerful method for
      mutation scanning of sequence variants. Denatured doubled-stranded DNA can be
      detected in fluorescence changes by increasing the melting temperature and wild
      type and heterozygous samples can be easily differentiated in the melting plots.
      HRM analysis represents the next generation of mutation-scanning technology and
      offers considerable time and cost savings compared to other screening methods.
      HRM analysis is a closed-tube method, indicating that polymerase chain reaction
      amplification and subsequent analysis are sequentially performed in the well,
      making HRM analysis more convenient than other scanning methodologies. Taken
      together, HRM analysis can be used for high-throughput mutation screening for
      research, as well as for molecular diagnostic and clinical purposes. This review
      summarizes the effectiveness of HRM analysis in the diagnosis of autosomal
      recessive, dominant, and X-linked genetic disorders. Notably, we will also
      discuss the limitations of HRM analysis and how to overcome them.

PMID- 22995430
TI  - Ongoing African measles virus genotype outbreak in Tel Aviv district since April,
      Israel, 2012.
AB  - A measles outbreak is affecting the Tel Aviv district, Israel, since April 2012.
      As of 10 September, 99 cases were confirmed, including 63 (64%) migrants of
      Eritrean and Sudanese origin. All genotyped cases had the African B3 genotype*.
      The mean age of migrant and non-migrant cases was 6.0+/-9.6 and 30.2+/-24.2
      years, respectively (p<0.001). The majority of both migrant and non-migrant cases
      was unvaccinated. This is the second African measles B3 genotype outbreak within
      the World Health Organization European region in 2012.

PMID- 22995431
TI  - An outbreak of Legionnaires' disease associated with a display spa pool in retail
      premises, Stoke-on-Trent, United Kingdom, July 2012.
AB  - Twenty-one confirmed cases of Legionnaires' disease (Legionella pneumophila
      serogroup 1) were identified in the Stoke-on-Trent area of England with onsets
      since 2 July 2012. Sequence-based typing results are available for nine cases;
      all are a unique type (ST1268). Initial interviews highlighted a number of
      possible environmental sources. Inspection of premises of interest revealed an
      operating spa pool on display, from which the outbreak strain was identified. All
      cases had visited the retail premise with this spa pool.

PMID- 22995432
TI  - Prevalence of Salmonella enterica serovar 4,[5],12:i:- in England and Wales,
      2010.
AB  - Difficulties in accurately identifying serovar 4,[5],12:i:- as monophasic
      variants of Salmonella enterica serovar Typhimurium mean there is confusion in
      the reporting of serovars Typhimurium and 4,[5],12:i:-. To gain insight into the
      prevalence and diversity of these monophasic variants in England and Wales,
      screening for fljB, hin and the serovar 4,[5],12:i:- DT193-associated genomic
      island was conducted on 609 S. enterica isolates designated as definitive phage
      type (DT) 193, and 142 isolates serologically-defined as monophasic variants of
      serovar Typhimurium but belonging to phage types other than DT193. All latter 142
      isolates were subtyped by multilocus variable-number tandem repeat analysis
      (MLVA). MLVA was also applied to 70 DT193 serologically-defined monophasic
      variant isolates. Results indicate that serovar 4,[5],12:i:- accounted for 108 of
      209 (52%) of DT193 isolates with available serological data and 99 of 142 (70%)
      monophasic variant isolates belonging to other phage types. Of 609 DT193
      isolates, 463 (76%) lacked fljB and hin. Moreover, genetically-related isolates
      of DTs 120, 191, 191a, 195, phage types U311 and U323, and reacts but does not
      conform (RDNC) and untypable (UT) strains were also lacking either hin and/or
      fljB. Of note, the serovar 4,[5],12:i:- DT193-associated genomic island was
      identified in not only 458 of 463 (99%) monophasic DT193 isolates, but also 25 of
      139 (18%) biphasic DT193 isolates and 56 of 76 (74%) monophasic variants of other
      phage types. Accurate monitoring of the emergence of serovar 4,[5],12:i:-
      isolates is important to ascertain the public health impact of these strains;
      since 2012 the Health Protection Agency's Salmonella Reference Unit has therefore
      begun determining full antigenic structures of all presumptive O:4 isolates in
      addition to routinely performing phage typing for identification of variants of
      serovar Typhimurium.

PMID- 22995433
TI  - Importance of standardisation of HAI definitions in interpretation of
      international and/or multinational prevalence studies.

PMID- 22995435
TI  - Health requirements for pilgrims attending the Hajj in Mecca, Kingdom of Saudi
      Arabia, 24-29 October 2012.

PMID- 22995436
TI  - Updated version of ECDC Guidance on human papillomavirus vaccines in Europe
      available.

PMID- 22995439
TI  - Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and
      hippocampus.
AB  - It has recently been reported that iron oxide nanoparticles (Fe(3)O(4)-NPs, 30
      nm) have the ability to translocate directly from the olfactory nerve to the
      brain. The striatum and hippocampus are important structures in the brain and are
      associated with the development of Parkinson's and Alzheimer's diseases.
      Therefore, it is critical to evaluate Fe(3)O(4)-NPs and their potential to confer
      striatum and hippocampus neurotoxicity. This study focuses on the effects of
      Fe(3)O(4)-NPs on the striatum and hippocampus, including oxidative injury and the
      accumulation and retention of Fe(3)O(4)-NPs. This study also explores the
      molecular mechanism of oxidative damage in dopaminergic neurons; we were able to
      assess the neurotoxic effects of Fe(3)O(4)-NPs by incubating dopaminergic neurons
      with radioactive Fe(3)O(4)-NPs. A regional distribution of Fe(3)O(4)-NPs was
      observed in rat brains after the particles were intranasally instilled for seven
      days. The particles were found to be deposited at particularly high
      concentrations in the rat striata and hippocampi. Over half of the Fe(3)O(4)-NPs
      were retained in the striata for a minimum of 14 days, and may have induced
      oxidative damage to the region. However, no injuries were observed in the
      hippocampi. These in vitro studies demonstrate that Fe(3)O(4)-NPs may decrease
      neuron viability, trigger oxidative stress, and activate JNK- and p53-mediated
      pathways to regulate the cell cycle and apoptosis. These results also suggest
      that environmental exposure to Fe(3)O(4)-NPs may play a role in the development
      of neurodegenerative diseases.

PMID- 22995440
TI  - Longitudinal evaluation of resting-state FMRI after acute stroke with
      hemiparesis.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) of motor impairment
      after stroke strongly depends on patient effort and capacity to make a movement.
      Hence fMRI has had limited use in clinical management. Alternatively, resting
      state fMRI (ie, with no task) can elucidate the brain's functional connections by
      determining temporal synchrony between brain regions. OBJECTIVE: The authors
      examined whether resting-state fMRI can elucidate the disruption of functional
      connections within hours of ischemic stroke as well as during recovery. METHODS:
      A total of 51 ischemic stroke patients--31 with mild-to-moderate hand deficits
      (National Institutes of Health Stroke Scale [NIHSS] motor score >=1) and 20 with
      NIHSS score of 0--underwent resting-state fMRI at <24 hours, 7 days, and 90 days
      poststroke; 15 age-matched healthy individuals participated in 1 session. Using
      the resting-state fMRI signal from the ipsilesional motor cortex, the strength of
      functional connections with the contralesional motor cortex was computed. Whole
      brain maps of the resting-state motor network were also generated and compared
      between groups and sessions. RESULTS: Within hours poststroke, patients with
      motor deficits exhibited significantly lower connectivity than controls (P = .02)
      and patients with no motor impairment (P = .03). Connectivity was reestablished
      after 7 days in recovered (ie, NIHSS score = 0) participants. After 90 days,
      recovered patients exhibited normal motor connectivity; however, reduced
      connectivity with subcortical regions associated with effort and cognitive
      processing remained. CONCLUSION: Resting-state fMRI within hours of ischemic
      stroke can demonstrate the impact of stroke on functional connections throughout
      the brain. This tool has the potential to help select appropriate stroke
      therapies in an acute imaging setting and to monitor the efficacy of
      rehabilitation.

PMID- 22995441
TI  - The usefulness of brain natriuretic peptide in simple congenital heart disease -
      a systematic review.
AB  - Brain natriuretic peptide and N-terminal pro-brain natriuretic peptide are two
      well-established markers for cardiac failure in acquired heart disease.
      Nevertheless, the clinical utility of these markers in patients with congenital
      heart disease remains unclear. Therefore, the aim of this study was to evaluate
      the diagnostic and prognostic value of these markers in patients with congenital
      heart disease. A PubMed and EMBASE literature search was executed with focus on
      the most common simple congenital heart defects, atrial septal defect and
      ventricular septal defect. Data on brain natriuretic peptide measurement, cardiac
      function parameters, and follow-up were collected. In patients with atrial or
      ventricular septal defect, brain natriuretic peptide levels were mildly increased
      when compared with healthy age-matched controls. Shunt severity and pulmonary
      artery pressure correlated strongly with natriuretic peptide levels. A clear
      association between brain natriuretic peptide and functional class was
      demonstrated. After closure of the defect, a rise in brain natriuretic peptide
      levels in the first hours to days was observed. After longer follow-up,
      natriuretic peptide levels decreased and became comparable to pre-procedural
      values. In conclusion, this systematic review shows that brain natriuretic
      peptide levels are mildly increased in patients with unrepaired and repaired
      atrial or ventricular septal defect. Brain natriuretic peptide measurement might
      be a useful additional tool in the diagnostic work-up of patients with atrial or
      ventricular septal defect. Further investigation in a larger, prospective study
      with long-term follow-up is warranted to elucidate the true prognostic value of
      natriuretic peptides in patients with simple congenital heart disease.

PMID- 22995442
TI  - The role of ectopic germinal centers in the immunopathology of primary Sjogren's
      syndrome: a systematic review.
AB  - OBJECTIVES: To determine whether the presence of germinal centers (GCs) in
      salivary glands of patients with primary Sjogren's syndrome (pSS) is related to
      the severity of disease course and distinct immunopathology features. METHODS: A
      systematic search was performed in September 2011 for terms and synonyms of
      Sjogren's syndrome and germinal centers. A total of 80 articles were retrieved,
      of which 16 were included for (meta-) analysis. RESULTS: GC morphology was
      present in a mean +/- SD 25.1 +/- 5.0% of pSS patients. Mean lymphocyte focus
      scores were 1.25 points higher in patients with GCs as compared to those without
      GCs. Saliva production was reduced in patients with GCs, although this did not
      reach statistical significance. Percentages of patients positive for rheumatoid
      factor, anti-Sjogren's syndrome A (SSA), and anti-Sjogren's syndrome B (SSB)
      antibodies were significantly higher in patients with GCs (mean increase, 15%,
      18%, and 18%, respectively). Additionally, patients with GCs were characterized
      by enhanced levels of local and systemic proinflammatory mediators. Importantly,
      these patients have a higher risk of lymphoma development (14% versus 1%).
      CONCLUSIONS: Patients with GCs are characterized by more severe disease, although
      the small number of studies and their design hamper generalizability of results.
      The precise mechanisms that contribute to the development and persistence of
      germinal centers in pSS are largely unknown. This and the strongly increased risk
      of lymphoma development warrant intensive studies for the role of germinal
      centers in the immunopathology of pSS.

PMID- 22995443
TI  - Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain
      derived neurotrophic factor, TrkB levels in rat induced by corticosterone
      administration.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hemerocallis citrina, a traditional herbal
      medicine, has been used for the improvement of behavioral and emotional status in
      Eastern-Asia countries. AIM OF THE STUDY: Our previous studies have demonstrated
      that the ethanol extracts of H. citrina flowers (HCE) reversed the behavioral
      alterations and monoamine neurotransmitter dysfunctions in stressed mice.
      However, the relation of its antidepressant-like action with neurotrophic
      molecular expressions remains unknown. MATERIALS AND METHODS: To clarify this, we
      explored the effect of HCE (32.5, 65, 130mg/kg, p.o.) on the behavior, brain
      derived neurotrophic factor (BDNF) and its receptor (TrkB) in depression-like
      rats induced by exogenous administration of the stress hormone corticosterone
      (40mg/kg, s.c.). RESULTS: It was observed that repeated administration of
      corticosterone induced an elevation on the serum corticosterone levels, which
      caused the abnormalities observed in the sucrose preference test and forced
      swimming test (FST). Administration of HCE (65 and 130mg/kg) reversed the changes
      above and up-regulated the BDNF and TrkB receptor protein expressions in the
      brain region of frontal cortex and hippocampus. CONCLUSION: These findings
      confirm that HCE produce an antidepressant-like effect in corticosterone-induced
      depression-like model of rats and this effect is at least partly mediated by BDNF
      TrkB signaling in the frontal cortex and hippocampus.

PMID- 22995444
TI  - In vitro and in vivo anticancer effects of Lithospermum erythrorhizon extract on
      B16F10 murine melanoma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lithospermum erythrorhizon has long been used in
      traditional Asian medicine for the treatment of diseases including skin cancer.
      In this study, hexane extract from the roots of Lithospermum erythrorhizon (LEH)
      was chemically characterized and its anticancer activity was tested against the
      most aggressive form of skin cancer. MATERIALS AND METHODS: The in vitro
      anticancer studies viz. cell growth, cell cycle and apoptosis, and the expression
      of tumor regulating proteins were analyzed against B16F10 melanoma cells. In
      addition, C57BL/6 mice models were used to evaluate the in vivo anticancer
      potential of LEH. Mice were intraperitoneally injected with LEH at doses of 0.1
      and 10mg/kg every 3 days. The tumor inhibition ratio was determined after 21 days
      of treatment and the histopathological analyses of the tumor tissues were
      compared. Further, LEH was purified and its active compounds were structurally
      elucidated and identified by NMR spectra and quantified by HPLC analyses.
      RESULTS: LEH effectively inhibits the growth of melanoma cells with an IC(50) of
      2.73MUg/ml. Cell cycle analysis revealed that LEH increased the percentage of
      cells in sub-G1 phase by dose dependent manner. LEH exhibited down regulation of
      anti-apoptotic Bcl-2 family proteins and up regulation of apoptotic Bax protein
      expression. Importantly, LEH induced cleavage of poly (ADP-ribose) polymerase
      (PARP) and activated the caspase cascade (caspase 3) with this cleavage mediating
      the apoptosis of B16F10 cells. LEH treatment at a dose of 10mg/kg for 21 days in
      experimental mice implanted with tumors resulted in significant reduction of the
      tumor growth (43%) and weight (36%). Histopathology analysis of LEH treated tumor
      tissues showed evidence of increased necrotic cells in a concentration dependent
      manner. Meanwhile, five naphthoquinone compounds [Shikonin (1); Deoxyshikonin
      (2); beta-Hydroxyisovalerylshikonin (3); Acetylshikonin (4) and
      Isobutyrylshikonin (5)] were purified from LEH and responsible for its anticancer
      activity. CONCLUSION: LEH induced apoptosis in B16F10 cells by activation of
      caspase 3 and inducing sub-G1 cell cycle arrest. LEH exhibited both in vitro and
      in vivo anticancer activity. Shikonin derivatives in the LEH are responsible for
      the anticancer activity.

PMID- 22995445
TI  - Individual differences in conceptual and procedural fraction understanding: the
      role of abilities and school experience.
AB  - Recent research on children's conceptual and procedural knowledge has suggested
      that there are individual differences in the ways that children combine these two
      types of knowledge across a number of mathematical topics. Cluster analyses have
      demonstrated that some children have more conceptual knowledge, some children
      have more procedural knowledge, and some children have an equal level of both.
      The current study investigated whether similar individual differences exist in
      children's understanding of fractions and searches for explanations for these
      differences. Grade 6 students (n=119) and Grade 8 students (n=114) were given
      measures of conceptual and procedural knowledge of fractions as well as measures
      of general fraction knowledge, general conceptual ability, and general procedural
      ability. Grade 6 children demonstrated a four-cluster solution reflecting those
      who do poorly on procedural and conceptual fraction knowledge, those who do well
      on both, those whose strength is procedural knowledge, and those whose strength
      is conceptual knowledge. Grade 8 children demonstrated a two-cluster solution
      reflecting those whose strength is procedural knowledge and those whose strength
      is conceptual knowledge. Cluster in either grade, however, did not vary in
      distribution across schools and was not related to general conceptual ability or
      general procedural ability. Overall, these results provide a more detailed
      picture of individual differences in conceptual and procedural knowledge in
      mathematical cognition.

PMID- 22995446
TI  - Body image and body type preferences in St. Kitts, Caribbean: a cross- cultural
      comparison with U.S. samples regarding attitudes towards muscularity, body fat,
      and breast size.
AB  - We investigated body image in St. Kitts, a Caribbean island where tourism,
      international media, and relatively high levels of body fat are common.
      Participants were men and women recruited from St. Kitts (n = 39) and, for
      comparison, U.S. samples from universities (n = 618) and the Internet (n = 438).
      Participants were shown computer generated images varying in apparent body fat
      level and muscularity or breast size and they indicated their body type
      preferences and attitudes. Overall, there were only modest differences in body
      type preferences between St. Kitts and the Internet sample, with the St. Kitts
      participants being somewhat more likely to value heavier women. Notably, however,
      men and women from St. Kitts were more likely to idealize smaller breasts than
      participants in the U.S. samples. Attitudes regarding muscularity were generally
      similar across samples. This study provides one of the few investigations of body
      preferences in the Caribbean.

PMID- 22995447
TI  - A survey of influence of work environment on temporomandibular disorders-related
      symptoms in Japan.
AB  - INTRODUCTION: This study aimed at identifying the factors that influence the
      incidence of temporomandibular disorders (TMD)-related symptoms (TRS) in a
      Japanese working population. METHODS: Our study subjects comprised of 1,969
      employees from the same Japanese company. The subjects were assessed using a
      questionnaire that covered both TRS and the work environment. TRS were measured
      from 4 items on the questionnaire. The work environment factors recorded were the
      daily mean duration of personal computer use, driving, precise work, commuting,
      time spent at home before going to bed, sleeping, attending business meetings,
      and performing physical labor. Statistical analysis was performed using t-tests,
      Chi-square tests, and logistic regression analyses. A result with P < 0.05 was
      considered statistically significant. RESULTS: The median total score on the 4
      items used to assess TRS was 5 (25% = 4, 75% = 7). Two groups were defined such
      that the participants scoring <=7 were assigned to the low-TRS group and those
      scoring >=8, to the high-TRS group. The high-TRS group constituted 22.6% of the
      subjects. Logistic regression analyses indicated that female gender and extended
      periods of computer use were significant contributors to the manifestation of
      TRS. CONCLUSION: This questionnaire-based study showed that gender and computer
      use time was associated with the prevalence of TRS in this working population.
      Thus, evaluation of ergonomics is suggested for TMD patients.

PMID- 22995448
TI  - Individuals with single versus multiple suicide attempts over 10years of
      prospective follow-up.
AB  - BACKGROUND: The study attempted to identify characteristics that differentiate
      multiple suicide attempters from single attempters in individuals with
      personality disorders (PDs) and/or major depression. METHOD: Participants were
      431 participants enrolled in the Collaborative Longitudinal Study of Personality
      Disorders from July 1996 to June 2008. Suicide attempts were assessed with the
      Longitudinal Interval Follow-up Evaluation at 6 and 12months, then yearly through
      10years. Logistic regression was used to compare single attempters to multiple
      attempters on Axis I and II psychiatric disorders and personality trait
      variables. RESULTS: Twenty-one percent of participants attempted suicide during
      the 10years of observation, with 39 (9.0%) reporting a single suicide attempt and
      54 (12.5%) reporting multiple suicide attempts. Although no significant
      differences in were found in baseline Axis I disorders, multiple attempters were
      significantly more likely to meet criteria for borderline personality disorder
      and to have higher impulsivity scores than single attempters. CONCLUSION: These
      results underscore the importance of considering both personality disorders and
      traits in the assessment of suicidality.

PMID- 22995449
TI  - Teaching evidence-based approaches to suicide risk assessment and prevention that
      enhance psychiatric training.
AB  - This report describes one in a series of National Institute of Health (NIH)
      supported conferences aimed at enhancing the ability of leaders of psychiatry
      residency training to teach research literacy and produce both clinician-scholars
      and physician-scientists in their home programs. Most psychiatry training
      directors would not consider themselves research scholars or even well-schooled
      in evidence based practice. Yet they are the front line educators to prepare
      tomorrow's psychiatrists to keep up with, critically evaluate, and in some cases
      actually participate in the discovery of new and emerging psychiatric knowledge.
      This annual conference is meant to help psychiatry training directors become more
      enthusiastic, knowledgeable and pedagogically prepared to create research
      friendly environments at their home institutions, so that more trainees will, in
      turn, become research literate, practice evidence-based psychiatry, and enter
      research fellowships and careers. The overall design of each year's meeting is a
      series of plenary sessions introducing participants to new information pertaining
      to the core theme of that year's meeting, integrated with highly interactive
      small group teaching sessions designed to consolidate knowledge and provide
      pragmatic teaching tools appropriate for residents at various levels of training.
      The theme of each meeting, selected to be a compelling and contemporary clinical
      problem, serves as a vehicle to capture training directors' attention while
      teaching relevant brain science, research literacy and effective pedagogy. This
      report describes the content and assessment of the 2011 annual pre-meeting,
      "Evidence-based Approaches to Suicide Risk Assessment and Prevention: Insights
      from the Neurosciences and Behavioral Sciences for use in Psychiatry Residency
      Training."

PMID- 22995450
TI  - Finders keepers: the features differentiating hoarding disorder from normative
      collecting.
AB  - OBJECTIVE: A new diagnostic category called Hoarding Disorder (HD) has been
      proposed for inclusion in DSM-5. It is paramount that this addition does not
      result in an over-pathologization of normative behavior. Collectors constitute a
      valid population within which to test the diagnostic boundaries of HD. The
      current study explored the features that differentiate pathological hoarding from
      normative collecting. METHODS: Participants were 29 individuals with a diagnosis
      of HD and 20 individuals who self-identified as collectors who enrolled in the
      London Field Trial for HD. A series of semi-structured interviews (often in the
      participants' homes) were conducted, including a detailed assessment of the
      typical elements of the collecting process. Participants also completed a battery
      of self-report questionnaires. RESULTS: Collectors were more likely than those
      with HD to be male, partnered, and free of psychiatric conditions or medication.
      Like those with HD, collectors reported the acquisition of, attachment to, and
      reluctance to discarding objects. However, the resulting clutter and impairment
      were minimal in this group and ultimately insufficient to garner an HD diagnosis.
      Collectors were, additionally, more focused in their acquisitions (e.g.,
      confining their accumulations to a narrow range of items), more selective (e.g.,
      planning and purchasing only pre-determined items), more likely to organize their
      possessions and less likely to accumulate in an excessive manner. CONCLUSIONS:
      There are important quantitative and qualitative differences between HD and
      normative collecting. For this reason, collectors are unlikely to be
      inappropriately pathologized by the introduction of HD.

PMID- 22995452
TI  - Sensing and analysis of soluble phosphates in environmental samples: a review.
AB  - Excess phosphate levels in water can lead to increased algal growth,
      eutrophication and reduced water quality. Phosphate levels in water are regulated
      by the EU through the Urban Waste Water Treatment Directive (annual mean total
      phosphorus concentrations of 1-2 mg/l) and the Water Framework Directive that
      will enforce "good ecological and chemical status" by 2015. Legislation is
      therefore driving the need for increased monitoring of soluble phosphate in
      water, escalating the desire for a direct, label free approach that could provide
      remote, continuous monitoring in real-time. The standard method for measuring
      soluble phosphate in water is a colourimetric technique developed in the 1960s.
      This colourimetric approach is difficult to adapt for on-line measurements, uses
      specific reagents which require safe disposal and thus incurs significant costs
      to the water industry when carried out on a large scale. This review considers
      optical and electrochemical sensors plus recent advances with synthetic receptors
      and molecularly imprinted polymers. Progress in the development of phosphate
      sensors, designed for use in a variety of disciplines, is highlighted with a view
      to adapting successful approaches for use in the water sector. Additional
      considerations include the need for long term stability, low maintenance,
      specificity for phosphate and the capability of measuring total phosphorus
      concentrations down to at least 1 mg/l, as required by legislation. A sensor that
      could directly measure soluble, inorganic phosphate concentrations would draw
      significant interest from the environment sector and other disciplines, including
      the agricultural, detergent and bio-medical industries.

PMID- 22995451
TI  - Spanish validation of the Premorbid Adjustment Scale (PAS-S).
AB  - BACKGROUND: The Premorbid Adjustment Scale (PAS) has been the most widely used
      scale to quantify premorbid status in schizophrenia, coming to be regarded as the
      gold standard of retrospective assessment instruments. AIMS: To examine the
      psychometric properties of the Spanish version of the PAS (PAS-S). METHOD:
      Retrospective study of 140 individuals experiencing a first episode of psychosis
      (n=77) and individuals who have schizophrenia (n=63), both adult and adolescent
      patients. Data were collected through a socio-demographic questionnaire and a
      battery of instruments which includes the following scales: PAS-S, PANSS, LSP,
      GAF and DAS-sv. The Cronbach's alpha was performed to assess the internal
      consistency of PAS-S. Pearson's correlations were performed to assess the
      convergent and discriminant validity. RESULTS: The Cronbach's alpha of the PAS-S
      scale was 0.85. The correlation between social PAS-S and total PAS-S was 0.85
      (p<0.001); while for academic PAS-S and total PAS-S it was 0.53 (p<0.001).
      Significant correlations were observed between all the scores of each age period
      evaluated across the PAS-S scale, with a significance value less than 0.001.
      There was a relationship between negative symptoms and social PAS-S (0.20,
      p<0.05) and total PAS-S (0.22, p<0.05), but not with academic PAS-S. However,
      there was a correlation between academic PAS-S and general subscale of the PANSS
      (0.19, p<0.05). Social PAS-S was related to disability measures (DAS-sv); and
      academic PAS-S showed discriminant validity with most of the variables of social
      functioning. PAS-S did not show association with the total LSP scale
      (discriminant validity). CONCLUSION: The Spanish version of the Premorbid
      Adjustment Scale showed appropriate psychometric properties in patients
      experiencing a first episode of psychosis and who have a chronic evolution of the
      illness. Moreover, each domain of the PAS-S (social and academic premorbid
      functioning) showed a differential relationship to other characteristics such as
      psychotic symptoms, disability or social functioning after onset of illness.

PMID- 22995453
TI  - Comparison of different doses of epsilon-aminocaproic acid in children for
      tetralogy of Fallot surgery: clinical efficacy and safety.
AB  - OBJECTIVE: The purpose of this study was to compare 2 different doses of epsilon
      aminocaproic acid (EACA) and assess their relative efficacy and safety in
      children undergoing corrective surgery for tetralogy of Fallot (TOF). DESIGN: A
      prospective, randomized, controlled study. SETTING: A tertiary care center.
      PARTICIPANTS: One hundred twenty children undergoing corrective surgery for TOF
      using cardiopulmonary bypass (CPB). INTERVENTIONS: Group 1 received 100 mg/kg of
      EACA after induction, upon initiation of CPB, and after protamine. Group 2
      received 75 mg/kg of EACA after induction, followed by a maintenance infusion of
      75 mg/kg/h until chest closure, and an additional 75 mg/kg upon initiation of
      CPB. Group 3 did not receive any antifibrinolytic agent or placebo. MEASUREMENT
      AND MAIN RESULTS: Cumulative mean blood loss, total packed red blood cells, and
      fresh frozen plasma requirements were significantly less in group 2 (p <= 0.01).
      There were no significant differences in the total platelet concentrate
      transfused, re-exploration rate, incidence of renal failure, arrhythmias,
      neurologic complications, mortality, or length of intensive care unit stay among
      the 3 groups. The incidences of perioperative ST/T changes and chest closure time
      were significantly less in group 1 and group 2 (p <= 0.01). The duration of
      mechanical ventilation was significantly less in group 2 (p <= 0.01).
      CONCLUSIONS: EACA was effective in reducing the postoperative blood loss and
      transfusion requirements in children undergoing corrective cardiac surgery on CPB
      for TOF. The dose regimen of 75 mg/kg after induction, followed by a maintenance
      infusion of 75 mg/kg/h until chest closure, and an additional 75 mg/kg upon
      initiation of CPB were more effective.

PMID- 22995454
TI  - Percutaneous closure of mitral paravalvular leak.

PMID- 22995455
TI  - Fibrinogen concentration significantly decreases after on-pump versus off-pump
      coronary artery bypass surgery: a systematic point-of-care ROTEM analysis.
AB  - OBJECTIVES: Studies have emphasized the importance of normal fibrinogen
      concentrations in surgical patients. The primary hypothesis of this study was
      that fibrinogen levels significantly decrease in on-pump coronary artery bypass
      graft (CABG) surgery versus off-pump coronary artery bypass graft (OPCAB)
      surgery. The second objective was to show that ROTEM (TEM International, GmbH,
      Munich, Germany) rapidly detects these abnormalities compared with standard
      tests. DESIGN: A prospective, nonrandomized study. SETTING: A university
      hospital. PARTICIPANTS: Forty-two and 62 patients in the CABG and OPCAB groups,
      respectively, undergoing first-time bypass surgery were included. INTERVENTIONS:
      CABG versus OPCAB surgery. MEASUREMENTS AND MAIN RESULTS: Routine coagulation
      tests and ROTEM values were measured before anesthesia (T0), after the first dose
      of heparin (T1), after protamine (T2), upon intensive care unit arrival (T3), and
      4 hours postoperatively (T4). The outcome measures were followed until 4 hours
      postoperatively. Fibrinogen concentrations were significantly lower in the CABG
      versus the OPCAB group at T2 (170 +/- 44 v 243 +/- 73 mg/dL, p < 0.001) and T3
      (179 +/- 42 v 232 +/- 68 mg/dL, p < 0.001). This was confirmed by significantly
      lower FIBTEM maximal clot firmness values at T2 (9 +/- 4 v 14 +/- 5 mm, p <
      0.001) and T3 (9 +/- 4 v 13 +/- 6 mm, p < 0.001). In the CABG group, patients
      received significantly more transfusions of all blood products except fresh
      frozen plasma. CONCLUSIONS: Fibrinogen concentration significantly decreases
      after cardiopulmonary bypass. ROTEM helps in its fast detection.

PMID- 22995456
TI  - Landmark-guided internal jugular vein cannulation: is there still a role and, if
      so, what should we do about it?

PMID- 22995457
TI  - Ultrasound-guided vascular access: a comprehensive review.

PMID- 22995458
TI  - Is a neutral head position as effective as head rotation during landmark-guided
      internal jugular vein cannulation? Results of a randomized controlled clinical
      trial.
AB  - OBJECTIVE: Central venous access remains a cornerstone procedure for a variety of
      clinical conditions. Ultrasound studies suggest that rotation of the head
      increases the magnitude of the overlap of the internal jugular vein with the
      carotid artery. The authors assessed whether a neutral position of the head
      during anatomic landmark-guided cannulation of the internal jugular vein (IJV)
      was an attractive alternative to rotating the neck to a >45 degrees  head turn.
      DESIGN: A prospective, randomized, controlled study. SETTING: An education and
      research hospital and a university-affiliated hospital. PARTICIPANTS: Eighty
      patients requiring central venous catheterization in the right IJV.
      INTERVENTIONS: Under general anesthesia, patients were positioned in the
      Trendelenburg position with extension of the neck. In the rotated group, the head
      was rotated to the left at >45 degrees . In the neutral group, the head was
      placed in the neutral position. Right IJV cannulation was performed using the
      central approach with the needle angled toward the ipsilateral nipple. The
      primary outcome variable was the cumulative success rate, which was defined as
      IJV puncture achieved in the first 3 attempts using a finder needle. A p value of
      <0.05 was considered statistically significant. MEASUREMENTS AND MAIN RESULTS:
      Groups were similar in terms of demographic data. The success rates of finder
      needle passes into the IJV on the first attempt were 87.5% and 37.5% (p < 0.05),
      and the cumulative success rates on the first 3 attempts were 97.5% and 57.5% in
      the rotated and neutral groups, respectively (p < 0.05). Carotid artery puncture
      only occurred in 2 patients in the rotated group. CONCLUSIONS: Because of the
      lower success rate, the neutral head position is not an attractive alternative
      for IJV catheterization when compared with the rotated head position in a central
      landmark IJV approach.

PMID- 22995459
TI  - Cerebral oximetry during cardiac surgery: the association between cerebral oxygen
      saturation and perioperative patient variables.
AB  - OBJECTIVE: This "real-world" study was designed to assess the patterns of
      regional cerebral oxygen saturation (rSO(2)) change during adult cardiac surgery.
      A secondary objective was to determine any relation between perioperative rSO(2)
      (baseline and during surgery) and patient characteristics or intraoperative
      variables. DESIGN: Prospective, observational, multicenter, nonrandomized
      clinical study. SETTING: Cardiac operating rooms at 3 academic medical centers.
      PARTICIPANTS: Ninety consecutive adult patients presenting for cardiac surgery
      with or without cardiopulmonary bypass. INTERVENTIONS: Patients received standard
      care at each institution plus bilateral forehead recordings of cerebral oxygen
      saturation with the 7600 Regional Oximeter System (Nonin Medical, Plymouth, MN).
      MEASUREMENTS AND MAIN RESULTS: The average baseline (before induction) rSO(2) was
      63.9 +/- 8.8% (range 41%-95%); preoperative hematocrit correlated with baseline
      rSO(2) (0.48% increase for each 1% increase in hematocrit, p = 0.008). The
      average nadir (lowest recorded rSO(2) for any given patient) was 54.9 +/- 6.6%
      and was correlated with on-pump surgery, baseline rSO(2), and height. Baseline
      rSO(2) was found to be an independent predictor of length of stay (hazard ratio
      1.044, confidence interval 1.02-1.07, for each percentage of baseline rSO(2)).
      CONCLUSIONS: In cardiac surgical patients, lower baseline rSO(2) value, on-pump
      surgery, and height were significant predictors of nadir rSO(2), whereas only
      baseline rSO(2) was a predictor of postoperative length of stay. These findings
      support previous research on the predictive value of baseline rSO(2) on length of
      stay and emphasize the need for further research regarding the clinical relevance
      of baseline rSO(2) and intraoperative changes.

PMID- 22995461
TI  - Variation in osteocyte lacunar morphology and density in the human femur--a
      synchrotron radiation micro-CT study.
AB  - In recent years there has been growing interest in the spatial properties of
      osteocytes (including density and morphology) and how these potentially relate to
      adaptation, disease and aging. This interest has, in part, arisen from the
      availability of increasingly high-resolution 3D imaging modalities such as
      synchrotron radiation (SR) micro-CT. As resolution increases, field of view
      generally decreases. Thus, while increasingly detailed spatial information is
      obtained, it is unclear how representative this information is of the skeleton or
      even the isolated bone. The purpose of this research was to describe the
      variation in osteocyte lacunar density, morphology and orientation within the
      femur from a healthy young male human. Multiple anterior, posterior, medial and
      lateral blocks (2 mm * 2 mm) were prepared from the proximal femoral shaft and SR
      micro-CT imaged at the Advanced Photon Source. Average lacunar densities (+/-
      standard deviation) from the anterior, posterior, medial and lateral regions were
      27,169 +/- 1935, 26,3643 +/- 1262, 37,521 +/- 6416 and 33,972 +/- 2513 lacunae
      per mm(3) of bone tissue, respectively. These values were significantly different
      between the medial and both the anterior and posterior regions (p<0.05). The
      density of the combined anterior and posterior regions was also significantly
      lower (p=0.001) than the density of the combined medial and lateral regions.
      Although no difference was found in predominant orientation, shape differences
      were found; with the combined anterior and posterior regions having more
      elongated (p=0.004) and flattened (p=0.045) lacunae, than those of the medial and
      lateral regions. This study reveals variation in osteocyte lacunar density and
      morphology within the cross-section of a single bone and that this variation can
      be considerable (up to 30% difference in density between regions). The underlying
      functional significance of the observed variation in lacunar density likely
      relates to localized variations in loading conditions as the pattern corresponds
      well with mechanical axes. Lower density and more elongate shapes being
      associated with the antero-posterior oriented neutral axis. Our findings
      demonstrate that the functional and pathological interpretations that are
      increasingly being drawn from high resolution imaging of osteocyte lacunae need
      to be better situated within the broader context of normal variation, including
      that which occurs even within a single skeletal element.

PMID- 22995462
TI  - Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants
      by impairing osteoblast differentiation.
AB  - Osseointegration is the process by which an orthopedic implant makes direct bone
      to-implant contact and is crucial for the long-term function of the implant.
      Surface contaminants, such as bacterial debris and manufacturing residues, may
      remain on orthopedic implants after sterilization and impair osseointegration.
      For example, specific lots of implants that were associated with impaired
      osseointegration and high failure rates were discovered to have contaminants
      including bacterial debris. Therefore, the goals of this study were to determine
      if bacterial debris exists on sterile orthopedic implants and if adherent
      bacterial debris inhibits the osseointegration of orthopedic implants. We found
      that debris containing lipopolysaccharide (LPS) from Gram-negative bacteria
      exists on both sterile craniofacial implants and wrist implants. Levels of
      bacterial debris vary not only between different lots of implants but within an
      individual lot. Using our murine model of osseointegration, we found that
      ultrapure LPS adherent to the implants inhibited bone-to-implant contact and
      biomechanical pullout measures. Analysis of osseointegration in knock-out mice
      demonstrated that adherent LPS inhibited osseointegration by signaling through
      its primary receptor, Toll-like receptor 4, and not by signaling through Toll
      like receptor 2. Ultrapure LPS adherent to titanium alloy discs had no detectable
      effect on early stages of MC3T3-E1 osteogenesis in vitro such as attachment,
      spreading or growth. However, later stages of osteogenic differentiation and
      mineralization were inhibited by adherent LPS. Thus, LPS may inhibit
      osseointegration in part through cell autonomous effects on osteoblasts. These
      results highlight bacterial debris as a type of surface contaminant that can
      impair the osseointegration of orthopedic implants.

PMID- 22995463
TI  - Accumulation of bone strontium measured by in vivo XRF in rats supplemented with
      strontium citrate and strontium ranelate.
AB  - Strontium ranelate is an approved pharmacotherapy for osteoporosis in Europe and
      Australia, but not in Canada or the United States. Strontium citrate, an
      alternative strontium salt, however, is available for purchase over-the-counter
      as a nutritional supplement. The effects of strontium citrate on bone are largely
      unknown. The study's objectives were 1) to quantify bone strontium accumulation
      in female Sprague Dawley rats administered strontium citrate (N=7) and compare
      these levels to rats administered strontium ranelate (N=6) and vehicle (N=6) over
      8 weeks, and 2) to verify an in vivo X-ray fluorescence spectroscopy (XRF) system
      for measurement of bone strontium in the rat. Daily doses of strontium citrate
      and strontium ranelate were determined with the intention to achieve equivalent
      amounts of elemental strontium. However, post-hoc analyses of each strontium
      compound conducted using energy dispersive spectrometry microanalysis revealed a
      higher elemental strontium concentration in strontium citrate than strontium
      ranelate. Bone strontium levels were measured at baseline and 8 weeks follow-up
      using a unique in vivo XRF technique previously used in humans. XRF measurements
      were validated against ex vivo measurements of bone strontium using inductively
      coupled plasma mass spectrometry. Weight gain in rats in all three groups was
      equivalent over the study duration. A two-way ANOVA was conducted to compare bone
      strontium levels amongst the three groups. Bone strontium levels in rats
      administered strontium citrate were significantly greater (p<0.05) than rats
      administered strontium ranelate and vehicle. ANCOVA analyses were performed with
      Sr dose as a covariate to account for differences in strontium dosing. The ANCOVA
      revealed differences in bone strontium levels between the strontium groups were
      not significant, but that bone strontium levels were still very significantly
      greater than vehicle.

PMID- 22995464
TI  - Effect of royal jelly ingestion for six months on healthy volunteers.
AB  - BACKGROUND: Royal jelly is a widely ingested supplement for health, but its
      effects on humans are not well known. The objective was to evaluate the effects
      of long-term royal jelly ingestion on humans. METHODS: We conducted a randomized
      placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42
      83 years were enrolled and were randomly divided into a royal jelly group (n =
      31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a
      placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes
      were changes in anthropometric measurements and biochemical indexes from baseline
      to 6 months after intervention. RESULTS: Thirty subjects in the RJ group and 26
      in the control group were included in the analysis of endpoints. In an adjusted
      mean change of the variables from the baseline, significant differences between
      the two groups could be found in red blood cell counts (+0.16x106/MUL for the RJ
      group vs. -0.01x106/MUL for the control group, P = 0.0134), hematocrit (+0.9% vs.
      -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 +/- 0.01 log mg/dL vs.
      +0.05 +/- 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. 
      0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log MUg/dL
      vs. +0.20 log MUg/dL, P = 0.0483), log testosterone (T) (+0.12 +/- 0.04 log ng/mL
      vs. -0.02 +/- 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 +/- 0.05 vs.
      -0.23 +/- 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental
      health (MH) (+4 vs. -7, P = 0.0276). CONCLUSIONS: Six-month ingestion of RJ in
      humans improved erythropoiesis, glucose tolerance and mental health. Acceleration
      of conversion from DHEA-S to T by RJ may have been observed among these favorable
      effects.

PMID- 22995465
TI  - Raman spectroscopic study of the hydroxy-phosphate mineral plumbogummite
      PbAl3(PO4)2(OH,H2O)6.
AB  - Plumbogummite PbAl(3)(PO(4))(2)(OH,H(2)O)(6) is a mineral of environmental
      significance and is a member of the alunite-jarosite supergroup. The molecular
      structure of the mineral has been investigated by Raman spectroscopy. The spectra
      of different plumbogummite specimens differ although there are many common
      features. The Raman spectra prove the spectral profile consisting of overlapping
      bands and shoulders. Raman bands and shoulders observed at 971, 980, 1002 and
      1023 cm(-1) (China sample) and 913, 981, 996 and 1026 cm(-1) (Czech sample) are
      assigned to the nu(1) symmetric stretching modes of the (PO(4))(3-), at 1002 and
      1023 cm(-1) (China) and 996 and 1026 cm(-1) to the nu(1) symmetric stretching
      vibrations of the (O(3)POH)(2-) units, and those at 1057, 1106 and 1182 (China)
      and at 1102, 1104 and 1179 cm(-1) (Czech) to the nu(3) (PO(4))(3-) and nu(3)
      (PO(3)) antisymmetric stretching vibrations. Raman bands and shoulders at 634,
      613 and 579 cm(-1) (China) and 611 and 596 cm(-1) (Czech) are attributed to the
      nu(4) (delta) (PO(4))(3-) bending vibrations and those at 507, 494 and 464 cm(-1)
      (China) and 505 and 464 cm(-1) (Czech) to the nu(2) (delta) (PO(4))(3-) bending
      vibrations. The Raman spectrum of the OH stretching region is complex. Raman
      bands and shoulders are identified at 2824, 3121, 3249, 3372, 3479 and 3602 cm(
      1) for plumbogummite from China, and at 3077, 3227, 3362, 3480, 3518 and 3601 cm(
      1) for the Czech Republic sample. These bands are assigned to the nu OH
      stretching modes of water molecules and hydrogen ions. Approximate O-H?O hydrogen
      bond lengths inferred from the Raman spectra vary in the range >3.2-2.62A (China)
      and >3.2-2.67A (Czech). The minority presence of some carbonate ions in the
      plumbogummite (China sample) is connected with distinctive intensity increasing
      of the Raman band at 1106 cm(-1), in which may participate the nu(1) (CO(3))(2-)
      symmetric stretching vibration overlapped with phosphate stretching vibrations.

PMID- 22995466
TI  - Hetero-binuclear near-infrared (NIR) luminescent Zn-Nd complexes self-assembled
      from the benzimidazole-based ligands.
AB  - With the compound [Zn(HL(1))(2)(Py)] (H(2)L(1)=2-(1H-benzo[d]imidazol-2-yl)-6
      methoxyophenol), Py=pyridine) or [Zn(HL(2))(2)(Py)] (H(2)L(2)=2-(1H
      benzo[d]imidazol-2-yl)-4-bromo-6-methoxyphenol) as the precursor, complexes
      [ZnLn(HL(1))(2)(Py)(NO(3))(3)] (Ln=Nd, 1; Ln=Gd, 2) or
      [ZnLn(HL(2))(2)(Py)(NO(3))(3)] (Ln=Nd, 3; Ln=Gd, 4) were obtained by the further
      reaction with Ln(NO(3))(3).6H(2)O (Ln=Nd or Gd). The result of their
      photophysical properties shows that the strong and characteristic near-infrared
      (NIR) luminescence of Nd(3+) ions for complexes 1 and 3 with emissive lifetimes
      in microsecond range, has been sensitized from the excited state ((1)LC and
      (3)LC) of the benzimidazole-based ligands, and the involvement of heavy atoms
      (Br) at the ligand endows the enhanced NIR luminescent property.

PMID- 22995467
TI  - Lipid adlayer organization mediated by a liquid overlayer.
AB  - We report on the formation of a chemically bound 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) monolayer on modified Au and silica surfaces, and changes
      in the organization of the interfacial lipid layer associated with immersion in
      aqueous solution. We have studied the interface using steady state and time
      resolved fluorescence spectroscopy, water contact angle and optical ellipsometry
      measurements, and electrochemical methods. Our data reveal that the DMPC adlayer
      in contact with air forms a relatively well organized interface that mediates the
      rotational motion of perylene. In the presence of an aqueous overlayer, perylene
      reorientation becomes more rapid, consistent with a reduction in the organization
      of the interfacial lipid adlayer. One implication of this finding is that the
      interfacial adlayer is less than a uniform monolayer, which is confirmed by
      electrochemical data. Our data underscore the importance of water in mediating
      the organization of interfacial lipid adlayers.

PMID- 22995468
TI  - Optical absorption and near infrared emissions of Nd3+ doped fluorophosphate
      glass.
AB  - Fluorophosphate glass doped with Nd(3+) has been synthesized with low OH content.
      Near infrared emissions centered around 0.9, 1.06, and 1.3 MUm have been
      successfully obtained in present glass excited by a conventional 800 nm laser
      diode. Based on the absorption spectrum, radiative properties were calculated and
      discussed using the Judd-Ofelt theory. The luminescence characteristics and
      energy transfer mechanism were investigated. Desirable low OH(-) concentration
      and spectroscopic characteristics of Nd(3+)-doped fluorophosphate glass indicate
      that it is a promising material for near-infrared lasers.

PMID- 22995469
TI  - Vibrational analyses of 1,3-dibenzoyl-4,5-dihydro-1H-imidazole-2-thione and 1,3
      dibenzoyl tetrahydropyrimidine-2(1H)-thione by normal coordinate treatment.
AB  - Vibrational analyses of 1,3-dibenzoyl-4,5-dihydro-1H-imidazole-2-thione and 1,3
      dibenzoyl tetrahydropyrimidine-2(1H)-thione were carried out using normal
      coordinate analysis. FT-IR spectra were recorded in the region 4000-400 cm(-1).
      The harmonic vibrational frequencies, molecular geometry and atomic charges have
      been computed, and NBO analysis has been carried out with the help of B3LYP
      density functional theory (DFT). The computed geometrical bond lengths and bond
      angles agree well with the crystallographic data. Atomic charges based on
      Mulliken population analysis, natural population analysis, Hirshfeld-I analysis
      and CHelpG analysis were calculated using the basis sets of 6-31G(*) and 6
      31G(**). Stabilities of the two molecules were analyzed by means of natural bond
      orbital (NBO) analysis and delocalized pi-pi(*) interactions.

PMID- 22995470
TI  - Effect of concentration of anionic polymethine dye in poly-N-epoxypropylcarbazole
      polymer film composite on the spectral-luminescent properties and
      photoconductivity.
AB  - The absorption, fluorescence and fluorescence excitation spectra of polymer thin
      film composites based on poly-N-epoxypropylcarbazole (PEPC) doped with different
      content of anionic polymethine dye testify to the formation of contact ion-pair
      associates at high concentration of the latter. The photoconductivity of such
      composites in the visible spectrum region is observed, despite the absence in the
      polymer of any fragment capable of accepting a photoexcited electron from anionic
      dye chromophore. Analysis of the spectral data together with DFT/B3LYP quantum
      chemical calculation of the HOMO and LUMO energies of the monomer N
      methylcarbazole unit and the radical of the polymethine dye allowed us to suggest
      the possible mechanism of internal photoeffect in the investigated composites
      which is based on the formation of the contact ion-pair associates.

PMID- 22995471
TI  - Synthesis, interaction with DNA and bovine serum albumin of the transition metal
      complexes of demethylcantharate and 2-aminobenzothiazole.
AB  - Four new transition metal complexes (Habtz)(2)[M(DCA)(2)].6H(2)O (M=Co(II) (1),
      Ni(II) (2), Cu(II) (3), Zn(II) (4); DCA=demethylcantharate, 7-oxabicyclo
      [2.2.1]heptane-2,3-dicarboxylate, C(8)H(8)O(5); Habtz=2-aminobenzothiazole acid,
      C(7)H(7)N(2)S) were synthesized and characterized by elemental analysis, molar
      conductance, infrared spectra and thermogravimetric analysis. The coordination
      number of complex was six. The X-ray diffraction analysis indicated that complex
      3 crystallized in the triclinic crystal system with P1- space group. The DNA
      binding properties of the complexes were investigated by electronic absorption
      spectra, fluorescence spectra, viscosity measurements. Title complexes could bind
      to DNA via partial intercalative mode. The K(b) of the complexes were 5.33*10(4)
      (1), 7.04*10(4) (2), 9.91*10(4) (3) and 5.03*10(4) L mol(-1) (4). The results of
      agarose gel electrophoresis showed that Cu(II) complex could cleave pBR322
      plasmid DNA via radical-based mechanism. The complexes could quench the intrinsic
      fluorescence of bovine serum albumin (BSA) through a static quenching with the
      binding constants K(a) of 1.11*10(4) (1), 1.24*10(6) (2), 8.42*10(5) (3) and
      1.75*10(4) L mol(-1) (4). The complexes had intense antiproliferative activities
      against human hepatoma cell lines (SMMC7721) and human gastric cancer cells
      (MGC80-3) lines in vitro. Cu(II) complex had the strongest activity against human
      gastric cancer cells.

PMID- 22995472
TI  - Lack of enhanced photocatalytic formation of iodine on particulate semiconductor
      mixtures.
AB  - Under UV-A light illumination, formation of iodine from iodide ion on the
      surfaces of anatase TiO(2), ZnO, Fe(2)O(3), CeO(2), MoO(3), Bi(2)O(3), and
      Nb(2)O(5) increases with the concentration of iodide ion, airflow rate and light
      intensity and conform to the Langmuir-Hinshelwood kinetic model. Measurement of
      the particle size of the semiconductor oxides by light scattering method and
      deduction of the same from the determined specific surface area show that the
      oxide particles agglomerate in suspension. However, mixtures of any two listed
      particulate semiconductors do not show enhanced photocatalytic formation of
      iodine indicating absence of interparticle charge transfer. The results are
      rationalized.

PMID- 22995473
TI  - InterSpread Plus: a spatial and stochastic simulation model of disease in animal
      populations.
AB  - We describe the spatially explicit, stochastic simulation model of disease
      spread, InterSpread Plus, in terms of its epidemiological framework, operation,
      and mode of use. The input data required by the model, the method for simulating
      contact and infection spread, and methods for simulating disease control measures
      are described. Data and parameters that are essential for disease simulation
      modelling using InterSpread Plus are distinguished from those that are non
      essential, and it is suggested that a rational approach to simulating disease
      epidemics using this tool is to start with core data and parameters, adding
      additional layers of complexity if and when the specific requirements of the
      simulation exercise require it. We recommend that simulation models of disease
      are best developed as part of epidemic contingency planning so decision makers
      are familiar with model outputs and assumptions and are well-positioned to
      evaluate their strengths and weaknesses to make informed decisions in times of
      crisis.

PMID- 22995474
TI  - Factors affecting European badger (Meles meles) capture numbers in one county in
      Ireland.
AB  - Understanding factors affecting the number of badgers captured at and around
      badger setts (burrows) is of considerable applied importance. These factors could
      be used to estimate probable badger densities for bovine tuberculosis (bTB)
      control and also for monitoring badger populations from a conservation
      perspective. Furthermore, badger management and vaccination programs would
      benefit by increasing the probability of efficiently capturing the target badger
      populations. Within this context, it was investigated whether badger capture
      numbers can be estimated from field signs and previous capture histories. Badger
      capture records (initial and repeated capture numbers at a sett) from a large
      scale removal program (405 km(2), 643 setts) were used. Univariable count models
      indicated that there were a number of significant potential predictors of badger
      numbers, during initial capture attempts. Using a multivariable zero-inflated
      Poisson (ZIP) model of initial captures we found that badger capture numbers were
      significantly affected by sett type, season, year, and the number of sett
      entrances in active use. Badger capture numbers were also affected by the total
      previous catch during repeated capture events and by the number of previous
      capture attempts. There was a significant negative trend in badger captures
      across events. Measures of the ability of these models to estimate badger
      captures suggested that the models might be useful in estimating badger numbers
      across a population; however the confidence intervals associated with these
      predictions were large.

PMID- 22995475
TI  - A novel function for p21Cip1 and acetyltransferase p/CAF as critical
      transcriptional regulators of TGFbeta-mediated breast cancer cell migration and
      invasion.
AB  - INTRODUCTION: Tumor cell migration and invasion are critical initiation steps in
      the process of breast cancer metastasis, the primary cause of breast cancer
      morbidity and death. Here we investigated the role of p21Cip1 (p21), a member of
      the core cell cycle machinery, in transforming growth factor-beta (TGFbeta)
      mediated breast cancer cell migration and invasion. METHODS: A mammary fat pad
      xenograft mouse model was used to assess the mammary tumor growth and local
      invasion. The triple negative human breast cancer cell lines MDA-MB231 and its
      sub-progenies SCP2 and SCP25, SUM159PT, SUM149PT, SUM229PE and SUM1315MO2 were
      treated with 5 ng/ml TGFbeta and the protein expression levels were measured by
      Western blot. Cell migration and invasion were examined using the scratch/wound
      healing and Transwell assay. TGFbeta transcriptional activity was measured by a
      TGFbeta/Smad reporter construct (CAGA12-luc) using luciferase assay. q-PCR was
      used for assessing TGFbeta downstream target genes. The interactions among p21,
      p/CAF and Smad3 were performed by co-immunoprecipitation. In addition, Smad3 on
      DNA binding ability was measured by DNA immunoprecipitation using biotinylated
      Smad binding element DNA probes. Finally, the association among active
      TGFbeta/Smad signaling, p21 and p/CAF with lymph node metastasis was examined by
      immunohistochemistry in tissue microarray containing 50 invasive ductal breast
      tumors, 25 of which are lymph node positive. RESULTS: We found p21 expression to
      correlate with poor overall and distant metastasis free survival in breast cancer
      patients. Furthermore, using xenograft animal models and in vitro studies, we
      found p21 to be essential for tumor cell invasion. The invasive effects of p21
      were found to correlate with Smad3, and p/CAF interaction downstream of TGFbeta.
      p21 and p/CAF regulates TGFbeta-mediated transcription of pro-metastatic genes by
      controlling Smad3 acetylation, DNA binding and transcriptional activity. In
      addition, we found that active TGFbeta/Smad signaling correlates with high p21
      and p/CAF expression levels and lymph node involvement using tissue microarrays
      from breast cancer patients. CONCLUSIONS: Together these results highlight an
      important role for p21 and p/CAF in promoting breast cancer cell migration and
      invasion at the transcriptional level and may open new avenues for breast cancer
      therapy.

PMID- 22995476
TI  - Cell signalling pathways that mediate haematopoietic stem cell specification.
AB  - Haematopoiesis is one of the most intensively studied and best described systems
      in the body. However, knowledge of cell signalling pathways that drive
      haematopoietic stem cell (HSC) development and how they interact with each other
      and with transcription factors that specify HSCs is still rudimentary. In this
      review, we will highlight recent advances in the field relating to these
      questions and identify gaps that need to be filled. To this end, we will briefly
      describe the developmental ontogeny of HSCs and examine in detail the cell
      signalling pathways that have been implicated in HSC specification. In conclusion
      we will discuss how this knowledge has led to the generation of blood cells in
      the laboratory and consider the implications of that advancement.

PMID- 22995477
TI  - The systemic inflammation-based Glasgow Prognostic Score: a decade of experience
      in patients with cancer.
AB  - Since the initial work, a decade ago that the combination of C-reactive protein
      and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value
      in patients with cancer, there have been more than 60 studies (>30,000 patients)
      that have examined and validated the use of the GPS or the modified GPS (mGPS) in
      a variety of cancer scenarios. The present review provides a concise overview of
      these studies and comments on the current and future clinical utility of this
      simple objective systemic inflammation-based score. The GPS/mGPS had independent
      prognostic value in (a) unselected cohorts (4 studies, >19,400 patients) (b)
      operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy (11
      studies, >1500 patients) (d) inoperable disease (11 studies, >2,000 patients).
      Association studies (15 studies, >2,000 patients) pointed to an increased
      GPS/mGPS being associated with increased weight and muscle loss, poor performance
      status, increased comorbidity, increased pro-inflammatory and angiogenic
      cytokines and complications on treatment. These studies have originated from 13
      different countries, in particular the UK and Japan. A chronic systemic
      inflammatory response, as evidenced by the GPS/mGPS, is clearly implicated in the
      prognosis of patients with cancer in a variety of clinical scenarios. The
      GPS/mGPS is the most extensively validated of the systemic inflammation-based
      prognostic scores and therefore may be used in the routine clinical assessment of
      patients with cancer. It not only identifies patients at risk but also provides a
      well defined therapeutic target for future clinical trials. It remains to be
      determined whether the GPS has prognostic value in other disease states.

PMID- 22995478
TI  - Long-term (up to 20 years) effects of 50-Hz magnetic field exposure on immune
      system and hematological parameters in healthy men.
AB  - OBJECTIVES: The relationship between exposure to 50-Hz magnetic fields and human
      health is of increasing interest since associations have been found in brain
      cancer in adults and childhood leukemia. In this study we investigate the
      possible chronic (up to 20 years) effects of exposure to magnetic fields in
      humans. DESIGN AND METHODS: We examined the nocturnal profiles of red blood
      cells, hemoglobin, hematocrit, platelets, mean platelet volume, total white blood
      cells, lymphocytes, monocytes, eosinophils, basophils, neutrophils, Ig
      (Immunoglobulin) A, IgM, IgG, CD (cluster of differentiation) 3, CD4, CD8,
      natural killer cells, B cells, total CD28, CD8+ CD28+, activated T cells,
      interleukin (IL)-2, IL-6, and IL-2 receptor, in 15 men exposed chronically and
      daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz
      magnetic field. The weekly geometric mean of individual exposures ranged from 0.1
      to 2.6 MUT. The results are compared to those of 15 unexposed men age-matched,
      with the same synchronization and physical activity that served as controls
      (individual exposures ranged from 0.004 to 0.092 MUT). Blood samples were taken
      hourly from 20:00 h to 08:00 h. RESULTS: Exposure over a long period and on a
      daily basis to magnetic fields resulted in no changes in the levels or patterns
      of hematological and immune system variables. CONCLUSIONS: Our data show that a
      long-term exposure to 50-Hz magnetic fields does not affect the hematological and
      immune system functions or their profile in healthy men, at least for the
      variables studied, and suggest that magnetic fields have no cumulative effects on
      these functions.

PMID- 22995479
TI  - Pitfalls in the genetic diagnosis of Hb S.
AB  - Patients homozygous for Hb S need to be properly identified to start as early as
      possible a treatment that should avoid complications. For prevention and genetic
      counseling, carriers of Hb S have to be screened. Hb S is easily detected by
      several analytical systems, but other variants, usually harmless, may behave as
      Hb S, leading to false positive diagnosis. Some interactions may also cause
      difficulties in the qualitative or quantitative interpretation of a
      chromatography or electrophoresis profile. These problems may result from several
      causes among which the simultaneous presence of an alpha chain variant leading to
      the formation of tetramers having both an alpha and a beta chain modified, the
      presence of a second mutation within the Hb S allele, the existence of a compound
      heterozygous state leading to some "Hb S trait with dominantly transmitted sickle
      cell disease (SCD)", and the presence of thalassemic allele affecting the
      intracellular proportion of Hb S. In case of any "dominant Hb S trait" a thorough
      Hb study is always required. This work reports some of the difficulties observed
      by us, or reported in the literature, and propose how to avoid them and reach a
      correct diagnosis.

PMID- 22995480
TI  - Evaluation of high-resolution mass spectrometry for urine toxicology screening in
      a pain management setting.
AB  - To evaluate liquid chromatography-high-resolution mass spectrometry (LC-HR-MS)
      for urine toxicology screening, 29 analytes were quantitated in 152 urine
      specimens from patients with chronic pain using two unique mass spectrometry
      platforms. De-identified specimens were quantitated in April of 2011 by liquid
      chromatography-triple quadrupole mass spectrometry (LC-MS-MS) and by full-scan LC
      HR-MS at Millennium Laboratories. Considering LC-MS-MS as the reference method,
      false positive results were identified in 19 specimens measured by LC-HR-MS.
      Application of relative retention times using deuterium labeled internal
      standards improved the rate of false positive detection to only five specimens,
      with four occurring for the same analyte. Ultra-high-resolution mass spectrometry
      (R = 100,000 at m/z 200) showed no improvement over high-resolution mass
      spectrometry (R = 10,000 at m/z 200) in the number of false positives detected.
      Quantitative results measured by LC-MS-MS and LC-HR-MS showed good agreement over
      four orders of dynamic range. This study demonstrates that LC-HR-MS is a suitable
      platform for toxicology screening for a pain management population and that
      quantitative accuracy and sensitivity are comparable to that achieved with LC-MS
      MS. The specificity of LC-HR-MS is improved by the addition of deuterium labeled
      internal standards and the implementation of relative retention time matching.

PMID- 22995481
TI  - Fatal metformin intoxication with markedly elevated blood and liver
      concentrations.
AB  - The highest postmortem metformin concentrations are recorded utilizing a
      sensitive and specific analytical procedure. The peripheral blood metformin
      concentration was 240 mg/L, the liver concentration was 240 mg/kg and the gastric
      concentration was 1,700 mg. Additionally, an antemortem blood sample collected
      shortly after admission revealed a metformin concentration of 210 mg/L. These
      data, revealing a liver to peripheral blood ratio of 1.0, provide additional
      support that metformin is not subject to postmortem redistribution. Intentional
      self-poisonings with metformin can result in death, despite multiple medical
      interventions.

PMID- 22995482
TI  - Rotational diffusion of membrane proteins: characterization of protein-protein
      interactions in membranes.

PMID- 22995483
TI  - Cellular response to heat shock studied by multiconfocal fluorescence correlation
      spectroscopy.
AB  - Heat shock triggers a transient and ubiquitous response, the function of which is
      to protect cells against stress-induced damage. The heat-shock response is
      controlled by a key transcription factor known as heat shock factor 1 (HSF1). We
      have developed a multiconfocal fluorescence correlation spectroscopy setup to
      measure the dynamics of HSF1 during the course of the heat-shock response. The
      system combines a spatial light modulator, to address several points of interest,
      and an electron-multiplying charge-coupled camera for fast multiconfocal
      recording of the photon streams. Autocorrelation curves with a temporal
      resolution of 14 MUs were analyzed before and after heat shock on eGFP and HSF1
      eGFP-expressing cells. Evaluation of the dynamic parameters of a diffusion-and
      binding model showed a slower HSF1 diffusion after heat shock. It is also
      observed that the dissociation rate decreases after heat shock, whereas the
      association rate is not affected. In addition, thanks to the multiconfocal
      fluorescence correlation spectroscopy system, up to five spots could be
      simultaneously located in each cell nucleus. This made it possible to quantify
      the intracellular variability of the diffusion constant of HSF1, which is higher
      than that of inert eGFP molecules and increases after heat shock. This finding is
      consistent with the fact that heat-shock response is associated with an increase
      of HSF1 interactions with DNA and cannot be explained even partially by heat
      induced modifications of nuclear organization.

PMID- 22995484
TI  - Magnetic tweezers-based force clamp reveals mechanically distinct apCAM domain
      interactions.
AB  - Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) play a crucial
      role in cell-cell interactions during nervous system development and function.
      The Aplysia CAM (apCAM), an invertebrate IgCAM, shares structural and functional
      similarities with vertebrate NCAM and therefore has been considered as the
      Aplysia homolog of NCAM. Despite these similarities, the binding properties of
      apCAM have not been investigated thus far. Using magnetic tweezers, we applied
      physiologically relevant, constant forces to apCAM-coated magnetic particles
      interacting with apCAM-coated model surfaces and characterized the kinetics of
      bond rupture. The average bond lifetime decreased with increasing external force,
      as predicted by theoretical considerations. Mathematical simulations suggest that
      the apCAM homophilic interaction is mediated by two distinct bonds, one involving
      all five immunoglobulin (Ig)-like domains in an antiparallel alignment and the
      other involving only two Ig domains. In summary, this study provides biophysical
      evidence that apCAM undergoes homophilic interactions, and that magnetic tweezers
      based, force-clamp measurements provide a rapid and reliable method for
      characterizing relatively weak CAM interactions.

PMID- 22995485
TI  - Effect of chain chirality on the self-assembly of sickle hemoglobin.
AB  - We present simulation results on the self-assembly behavior of sickle hemoglobin
      (HbS). A coarse-grained HbS model, which contains hydrophilic and hydrophobic
      particles explicitly, is constructed to match the structural properties and
      physical description of HbS. The hydrophobic interactions are shown to be
      necessary with chirality being the main driver for the formation of HbS fibers.
      In the absence of chain chirality, only small self-assembled aggregates are
      observed whereas self-assembled elongated steplike bundle microstructures appear
      when we include chain chirality. We also investigate the effect of confinement on
      self-assembly, and find that elongated fibers-similar to open-space ones-can be
      obtained in hard confinement domains but cannot be formed within compliant red
      blood cell (RBC) domains under the same assumptions. We show, however, that by
      placing explicitly HbS fibers inside the RBCs and subjecting them to linear
      elongation and bending, we obtain different types of sickle-shaped RBCs as
      observed in sickle cell anemia.

PMID- 22995486
TI  - Computational modeling of single-cell migration: the leading role of
      extracellular matrix fibers.
AB  - Cell migration is vitally important in a wide variety of biological contexts
      ranging from embryonic development and wound healing to malignant diseases such
      as cancer. It is a very complex process that is controlled by intracellular
      signaling pathways as well as the cell's microenvironment. Due to its importance
      and complexity, it has been studied for many years in the biomedical sciences,
      and in the last 30 years it also received an increasing amount of interest from
      theoretical scientists and mathematical modelers. Here we propose a force-based,
      individual-based modeling framework that links single-cell migration with matrix
      fibers and cell-matrix interactions through contact guidance and matrix
      remodelling. With this approach, we can highlight the effect of the cell's
      environment on its migration. We investigate the influence of matrix stiffness,
      matrix architecture, and cell speed on migration using quantitative measures that
      allow us to compare the results to experiments.

PMID- 22995488
TI  - Flow loading induces oscillatory trajectories in a bloodstream parasite.
AB  - The dynamics of isolated microswimmers are studied in bounded flow using the
      African trypanosome, a unicellular parasite, as the model organism. With the help
      of a microfluidics platform, cells are subjected to flow and found to follow an
      oscillatory path that is well fit by a sine wave. The frequency and amplitudes of
      the oscillatory trajectories are dependent on the flow velocity and cell
      orientation. When traveling in such a manner, trypanosomes orient upstream while
      downstream-facing cells tumble within the same streamline. A comparison with
      immotile trypanosomes demonstrates that self-propulsion is essential to the
      trajectories of trypanosomes even at flow velocities up to ~40 times higher than
      their own swimming speed. These studies reveal important swimming dynamics that
      may be generally pertinent to the transport of microswimmers in flow and may be
      relevant to microbial pathogenesis.

PMID- 22995487
TI  - Transcription stochasticity of complex gene regulation models.
AB  - Transcription is regulated by a multitude of factors that concertedly induce
      genes to switch between activity states. Eukaryotic transcription involves a
      multitude of complexes that sequentially assemble on chromatin under the
      influence of transcription factors and the dynamic state of chromatin.
      Prokaryotic transcription depends on transcription factors, sigma-factors, and,
      in some cases, on DNA looping. We present a stochastic model of transcription
      that considers these complex regulatory mechanisms. We coarse-grain the molecular
      details in such a way that the model can describe a broad class of gene
      regulation mechanisms. We solve this model analytically for various measures of
      stochastic transcription and compare alternative gene-regulation designs. We find
      that genes with complex multiprotein regulation can have peaked burst-size
      distributions in contrast to the geometric distributions found for simple models
      of transcription regulation. Burst-size distributions are, in addition, shaped by
      mRNA degradation during transcription bursts. We derive the stochastic properties
      of genes in the limit of deterministic switch times. These genes typically have
      reduced transcription noise. Severe timescale separation between gene regulation
      and transcription initiation enhances noise and leads to bimodal mRNA copy number
      distributions. In general, complex mechanisms for gene regulation lead to
      nonexponential waiting-time distributions for gene switching and transcription
      initiation, which typically reduce noise in mRNA copy numbers and burst size.
      Finally, we discuss that qualitatively different gene regulation models can often
      fit the same experimental data on single-cell mRNA abundance even though they
      have qualitatively different burst-size statistics and regulatory parameters.

PMID- 22995489
TI  - PIP3 waves and PTEN dynamics in the emergence of cell polarity.
AB  - In a motile eukaryotic cell, front protrusion and tail retraction are
      superimposed on each other. To single out mechanisms that result in front to tail
      or in tail to front transition, we separated the two processes in time using
      cells that oscillate between a full front and a full tail state. State
      transitions were visualized by total internal reflection fluorescence microscopy
      using as a front marker PIP3 (phosphatidylinositol [3,4,5] tris-phosphate), and
      as a tail marker the tumor-suppressor PTEN (phosphatase tensin homolog) that
      degrades PIP3. Negative fluctuations in the PTEN layer of the membrane gated a
      local increase in PIP3. In a subset of areas lacking PTEN (PTEN holes), PIP3 was
      amplified until a propagated wave was initiated. Wave propagation implies that a
      PIP3 signal is transmitted by a self-sustained process, such that the temporal
      and spatial profiles of the signal are maintained during passage of the wave
      across the entire expanse of the cell membrane. Actin clusters were remodeled
      into a ring along the perimeter of the expanding PIP3 wave. The reverse
      transition of PIP3 to PTEN was linked to the previous site of wave initiation:
      where PIP3 decayed first, the entry of PTEN was primed.

PMID- 22995490
TI  - Thermal transitions of fibrillar collagen unveiled by second-harmonic generation
      microscopy of corneal stroma.
AB  - The thermal transitions of fibrillar collagen are investigated with second
      harmonic generation polarization anisotropy microscopy. Second-harmonic
      generation images and polarization anisotropy profiles of corneal stroma heated
      in the 35-80 degrees C range are analyzed by means of a theoretical model that is
      suitable to probe principal intramolecular and interfibrillar parameters of
      immediate physiological interest. Our results depict the tissue modification with
      temperature as the interplay of three destructuration stages at different
      hierarchical levels of collagen assembly including its tertiary structure and
      interfibrillar alignment, thus supporting and extending previous findings. This
      method holds the promise of a quantitative inspection of fundamental biophysical
      and biochemical processes and may find future applications in real-time and
      postsurgical functional imaging of collagen-rich tissues subjected to thermal
      treatments.

PMID- 22995491
TI  - Cell mechanics, structure, and function are regulated by the stiffness of the
      three-dimensional microenvironment.
AB  - This study adopts a combined computational and experimental approach to determine
      the mechanical, structural, and metabolic properties of isolated chondrocytes
      cultured within three-dimensional hydrogels. A series of linear elastic and
      hyperelastic finite-element models demonstrated that chondrocytes cultured for 24
      h in gels for which the relaxation modulus is <5 kPa exhibit a cellular Young's
      modulus of ~5 kPa. This is notably greater than that reported for isolated
      chondrocytes in suspension. The increase in cell modulus occurs over a 24-h
      period and is associated with an increase in the organization of the cortical
      actin cytoskeleton, which is known to regulate cell mechanics. However, there was
      a reduction in chromatin condensation, suggesting that changes in the nucleus
      mechanics may not be involved. Comparison of cells in 1% and 3% agarose showed
      that cells in the stiffer gels rapidly develop a higher Young's modulus of ~20
      kPa, sixfold greater than that observed in the softer gels. This was associated
      with higher levels of actin organization and chromatin condensation, but only
      after 24 h in culture. Further studies revealed that cells in stiffer gels
      synthesize less extracellular matrix over a 28-day culture period. Hence, this
      study demonstrates that the properties of the three-dimensional microenvironment
      regulate the mechanical, structural, and metabolic properties of living cells.

PMID- 22995492
TI  - K+ conduction and Mg2+ blockade in a shaker Kv-channel single point mutant with
      an unusually high conductance.
AB  - Potassium channels exhibit a large diversity of single-channel conductances.
      Shaker is a low-conductance K-channel in which Pro475->Asp, a single-point
      mutation near the internal pore entrance, promotes 6- to 8-fold higher unitary
      current. To assess the mechanism for this higher conductance, we measured Shaker
      P475D single-channel current in a wide range of symmetrical K(+) concentrations
      and voltages. Below 300 mM K(+), the current-to-voltage relations (i-V) showed
      inward rectification that disappeared at 1000 mM K(+). Single-channel conductance
      reached a maximum of ~190 pS at saturating [K(+)], a value 4- to 5-fold larger
      than that estimated for the native channel. Intracellular Mg(2+) blocked this
      variant with ~100-fold higher affinity. Near zero voltage, blockade was
      competitively antagonized by K(+); however, at voltages >100 mV, it was enhanced
      by K(+). This result is consistent with a lock-in effect in a single-file
      diffusion regime of Mg(2+) and K(+) along the pore. Molecular-dynamics
      simulations revealed higher K(+) density in the pore, especially near the Asp-475
      side chains, as in the high-conductance MthK bacterial channel. The molecular
      dynamics also showed that K(+) ions bound distally can coexist with other K(+) or
      Mg(2+) in the cavity, supporting a lock-in mechanism. The maximal K(+) transport
      rate and higher occupancy could be due to a decrease in the electrostatic energy
      profile for K(+) throughout the pore, reducing the energy wells and barriers
      differentially by ~0.7 and ~2 kT, respectively.

PMID- 22995494
TI  - On the thermodynamic efficiency of Ca2+-ATPase molecular machines.
AB  - Experimental studies have shown that the activity of the reconstituted molecular
      pump Ca(2+)-ATPase strongly depends on the thickness of the supporting bilayer.
      It is thus expected that the bilayer structure will have an impact on the
      thermodynamic efficiency of this nanomachine. Here, we introduce a nonequilibrium
      thermodynamics theoretical approach to estimate the thermodynamic efficiency of
      the Ca(2+)-ATPase from analysis of available experimental data about ATP
      hydrolysis and Ca(2+) transport. We find that the entropy production, i.e., the
      heat released to the surroundings under working conditions, is approximately
      constant for bilayers containing phospholipids with hydrocarbon chains of 18-22
      carbon atoms. Our estimates for the heat released during the pump operation agree
      with results obtained from separate calorimetric experiments on the Ca(2+)-ATPase
      derived from sarcoplasmic reticulum. We show that the thermodynamic efficiency of
      the reconstituted Ca(2+)-ATPase reaches a maximum for bilayer thicknesses
      corresponding to maximum activity. Surprisingly, the estimated thermodynamic
      efficiency is very low, ~12%. We discuss the significance of this result as
      representative of the efficiency of other nanomachines, and we address the
      influence of the experimental set-up on such a low efficiency. Overall, our
      approach provides a general route to estimate thermodynamic efficiencies and heat
      dissipation in experimental studies of nanomachines.

PMID- 22995493
TI  - Interactions of high-affinity cationic blockers with the translocation pores of
      B. anthracis, C. botulinum, and C. perfringens binary toxins.
AB  - Cationic beta-cyclodextrin derivatives were recently introduced as highly
      effective, potentially universal blockers of three binary bacterial toxins:
      anthrax toxin of Bacillus anthracis, C2 toxin of Clostridium botulinum, and iota
      toxin of Clostridium perfringens. The binary toxins are made of two separate
      components: the enzymatic A component, which acts on certain intracellular
      targets, and the binding/translocation B component, which forms oligomeric
      channels in the target cell membrane. Here we studied the voltage and salt
      dependence of the rate constants of binding and dissociation reactions of two
      structurally different beta-cyclodextrins (AmPrbetaCD and AMBnTbetaCD) in the
      PA(63), C2IIa, and Ib channels (B components of anthrax, C2, and iota toxins,
      respectively). With all three channels, the blocker carrying extra hydrophobic
      aromatic groups on the thio-alkyl linkers of positively charged amino groups,
      AMBnTbetaCD, demonstrated significantly stronger binding compared with
      AmPrbetaCD. This effect is seen as an increased residence time of the blocker in
      the channels, whereas the time between blockages characterizing the binding
      reaction on-rate stays practically unchanged. Surprisingly, the voltage
      sensitivity, expressed as a slope of the logarithm of the blocker residence time
      as a function of voltage, turned out to be practically the same for all six cases
      studied, suggesting structural similarities among the three channels. Also, the
      more-effective AMBnTbetaCD blocker shows weaker salt dependence of the binding
      and dissociation rate constants compared with AmPrbetaCD. By estimating the
      relative contributions of the applied transmembrane field, long-range Coulomb,
      and salt-concentration-independent, short-range forces, we found that the latter
      represent the leading interaction, which accounts for the high efficiency of
      blockage. In a search for the putative groups in the channel lumen that are
      responsible for the short-range forces, we performed measurements with the F427A
      mutant of PA(63), which lacks the functionally important phenylalanine clamp. We
      found that the on-rates of the blockage were virtually conserved, but the
      residence times and, correspondingly, the binding constants dropped by more than
      an order of magnitude, which also reduced the difference between the efficiencies
      of the two blockers.

PMID- 22995495
TI  - Robust driving forces for transmembrane helix packing.
AB  - The packing structures of transmembrane helices are traditionally attributed to
      patterns in residues along the contact surface. In this view, besides keeping the
      helices confined in the membrane, the bilayer has only a minor effect on the
      helices structure. Here, we use two different approaches to show that the lipid
      environment has a crucial effect in determining the cross-angle distribution of
      packed helices. We analyzed structural data of a membrane proteins database. We
      show that the distribution of cross angles of helix pairs in this database is
      statistically indistinguishable from the cross-angle distribution of two
      noninteracting helices imbedded in the membrane. These results suggest that the
      cross angle is, to a large extent, determined by the tilt angle of the individual
      helices. We test this hypothesis using molecular simulations of a coarse-grained
      model that contains no specific residue interactions. These simulations reproduce
      the same cross-angle distribution as found in the database. As the tilt angle of
      a helix is dominated by hydrophobic mismatch between the protein and surrounding
      lipids, our results indicate that hydrophobic mismatch is the dominant factor
      guiding the transmembrane helix packing. Other short-range forces might then fine
      tune the structure to its final configuration.

PMID- 22995496
TI  - Interfacial tension and surface pressure of high density lipoprotein, low density
      lipoprotein, and related lipid droplets.
AB  - Lipid droplets play a central role in energy storage and metabolism on a cellular
      scale. Their core is comprised of hydrophobic lipids covered by a surface region
      consisting of amphiphilic lipids and proteins. For example, high and low density
      lipoproteins (HDL and LDL, respectively) are essentially lipid droplets
      surrounded by specific proteins, their main function being to transport
      cholesterol. Interfacial tension and surface pressure of these particles are of
      great interest because they are related to the shape and the stability of the
      droplets and to protein adsorption at the interface. Here we use coarse-grained
      molecular-dynamics simulations to consider a number of related issues by
      calculating the interfacial tension in protein-free lipid droplets, and in HDL
      and LDL particles mimicking physiological conditions. First, our results suggest
      that the curvature dependence of interfacial tension becomes significant for
      particles with a radius of ~5 nm, when the area per molecule in the surface
      region is <1.4 nm(2). Further, interfacial tensions in the used HDL and LDL
      models are essentially unaffected by single apo-proteins at the surface. Finally,
      interfacial tensions of lipoproteins are higher than in thermodynamically stable
      droplets, suggesting that HDL and LDL are kinetically trapped into a metastable
      state.

PMID- 22995497
TI  - How lipid headgroups sense the membrane environment: an application of 14N NMR.
AB  - The orientation of lipid headgroups may serve as a powerful sensor of
      electrostatic interactions in membranes. As shown previously by (2)H NMR
      measurements, the headgroup of phosphatidylcholine (PC) behaves like an
      electrometer and varies its orientation according to the membrane surface charge.
      Here, we explored the use of solid-state (14)N NMR as a relatively simple and
      label-free method to study the orientation of the PC headgroup in model membrane
      systems of varying composition. We found that (14)N NMR is sufficiently sensitive
      to detect small changes in headgroup orientation upon introduction of positively
      and negatively charged lipids and we developed an approach to directly convert
      the (14)N quadrupolar splittings into an average orientation of the PC polar
      headgroup. Our results show that inclusion of cholesterol or mixing of lipids
      with different length acyl chains does not significantly affect the orientation
      of the PC headgroup. In contrast, measurements with cationic (KALP), neutral (Ac
      KALP), and pH-sensitive (HALP) transmembrane peptides show very systematic
      changes in headgroup orientation, depending on the amount of charge in the
      peptide side chains and on their precise localization at the interface, as
      modulated by varying the extent of hydrophobic peptide/lipid mismatch. Finally,
      our measurements suggest an unexpectedly strong preferential enrichment of the
      anionic lipid phosphatidylglycerol around the cationic KALP peptide in ternary
      mixtures with PC. We believe that these results are important for understanding
      protein/lipid interactions and that they may help parametrization of membrane
      properties in computational studies.

PMID- 22995498
TI  - Kinetic mechanism of Ca2+-controlled changes of skeletal troponin I in psoas
      myofibrils.
AB  - Conformational changes in the skeletal troponin complex (sTn) induced by rapidly
      increasing or decreasing the [Ca(2+)] were probed by 5-iodoacetamidofluorescein
      covalently bound to Cys-133 of skeletal troponin I (sTnI). Kinetics of
      conformational changes was determined for the isolated complex and after
      incorporating the complex into rabbit psoas myofibrils. Isolated and incorporated
      sTn exhibited biphasic Ca(2+)-activation kinetics. Whereas the fast phase
      (k(obs)~1000 s(-1)) is only observed in this study, where kinetics were induced
      by Ca(2+), the slower phase resembles the monophasic kinetics of sTnI switching
      observed in another study (Brenner and Chalovich. 1999. Biophys. J. 77:2692-2708)
      that investigated the sTnI switching induced by releasing the feedback of force
      generating cross-bridges on thin filament activation. Therefore, the slower
      conformational change likely reflects the sTnI switch that regulates force
      development. Modeling reveals that the fast conformational change can occur after
      the first Ca(2+) ion binds to skeletal troponin C (sTnC), whereas the slower
      change requires Ca(2+) binding to both regulatory sites of sTnC. Incorporating
      sTn into myofibrils increased the off-rate and lowered the Ca(2+) sensitivity of
      sTnI switching. Comparison of switch-off kinetics with myofibril force relaxation
      kinetics measured in a mechanical setup indicates that sTnI switching might limit
      the rate of fast skeletal muscle relaxation.

PMID- 22995499
TI  - Self-organization of myosin II in reconstituted actomyosin bundles.
AB  - Cells assemble a variety of bundled actomyosin structures in the cytoskeleton for
      activities such as cell-shape regulation, force production, and cytokinesis.
      Although these linear structures exhibit varied architecture, two common
      organizational themes are a punctate distribution of myosin II and distinct
      patterns of actin polarity. The mechanisms that cells use to assemble and
      maintain these organizational features are poorly understood. To study these, we
      reconstituted actomyosin bundles in vitro that contained only actin filaments and
      myosin II. Upon addition of ATP, the bundles contracted and the uniformly
      distributed myosin spontaneously reorganized into discrete clusters. We developed
      a mathematical model in which the motion of myosin II filaments is governed by
      the polarities of the actin filaments with which they interact. The model showed
      that the assembly of myosins into clusters is driven by their tendency to migrate
      to locations with zero net actin filament polarity. With no fitting parameters,
      the predicted distribution of myosin cluster separations was in close agreement
      with our experiments, including a -3/2 power law decay for intermediate length
      scales. Thus, without an organizing template or accessory proteins, a minimal
      bundle of actin and myosin has the inherent capacity to self-organize into a
      heterogeneous banded structure.

PMID- 22995500
TI  - Thick-to-thin filament surface distance modulates cross-bridge kinetics in
      Drosophila flight muscle.
AB  - The demembranated (skinned) muscle fiber preparation is widely used to
      investigate muscle contraction because the intracellular ionic conditions can be
      precisely controlled. However, plasma membrane removal results in a loss of
      osmotic regulation, causing abnormal hydration of the myofilament lattice and its
      proteins. We investigated the structural and functional consequences of varied
      myofilament lattice spacing and protein hydration on cross-bridge rates of force
      development and detachment in Drosophila melanogaster indirect flight muscle,
      using x-ray diffraction to compare the lattice spacing of dissected, osmotically
      compressed skinned fibers to native muscle fibers in living flies. Osmolytes of
      different sizes and exclusion properties (Dextran T-500 and T-10) were used to
      differentially alter lattice spacing and protein hydration. At in vivo lattice
      spacing, cross-bridge attachment time (t(on)) increased with higher osmotic
      pressures, consistent with a reduced cross-bridge detachment rate as myofilament
      protein hydration decreased. In contrast, in the swollen lattice, t(on) decreased
      with higher osmotic pressures. These divergent responses were reconciled using a
      structural model that predicts t(on) varies inversely with thick-to-thin filament
      surface distance, suggesting that cross-bridge rates of force development and
      detachment are modulated more by myofilament lattice geometry than protein
      hydration. Generalizing these findings, our results suggest that cross-bridge
      cycling rates slow as thick-to-thin filament surface distance decreases with
      sarcomere lengthening, and likewise, cross-bridge cycling rates increase during
      sarcomere shortening. Together, these structural changes may provide a mechanism
      for altering cross-bridge performance throughout a contraction-relaxation cycle.

PMID- 22995501
TI  - Weak intra-ring allosteric communications of the archaeal chaperonin thermosome
      revealed by normal mode analysis.
AB  - Chaperonins are molecular machines that use ATP-driven cycles to assist misfolded
      substrate proteins to reach the native state. During the functional cycle, these
      machines adopt distinct nucleotide-dependent conformational states, which reflect
      large-scale allosteric changes in individual subunits. Distinct allosteric
      kinetics has been described for the two chaperonin classes. Bacterial (group I)
      chaperonins, such as GroEL, undergo concerted subunit motions within each ring,
      whereas archaeal and eukaryotic chaperonins (group II) undergo sequential subunit
      motions. We study these distinct mechanisms through a comparative normal mode
      analysis of monomer and double-ring structures of the archaeal chaperonin
      thermosome and GroEL. We find that thermosome monomers of each type exhibit
      common low-frequency behavior of normal modes. The observed distinct higher
      frequency modes are attributed to functional specialization of these subunit
      types. The thermosome double-ring structure has larger contribution from higher
      frequency modes, as it is found in the GroEL case. We find that long-range
      intersubunit correlation of amino-acid pairs is weaker in the thermosome ring
      than in GroEL. Overall, our results indicate that distinct allosteric behavior of
      the two chaperonin classes originates from different wiring of individual
      subunits as well as of the intersubunit communications.

PMID- 22995502
TI  - Elucidating the locking mechanism of peptides onto growing amyloid fibrils
      through transition path sampling.
AB  - We investigate the molecular mechanism of monomer addition to a growing amyloid
      fibril composed of the main amyloidogenic region from the insulin peptide
      hormone, the LVEALYL heptapeptide. Applying transition path sampling in
      combination with reaction coordinate analysis reveals that the transition from a
      docked peptide to a locked, fully incorporated peptide can occur in two ways.
      Both routes involve the formation of backbone hydrogen bonds between the three
      central amino acids of the attaching peptide and the fibril, as well as a
      reorientation of the central Glu side chain of the locking peptide toward the
      interface between two beta-sheets forming the fibril. The mechanisms differ in
      the sequence of events. We also conclude that proper docking is important for
      correct alignment of the peptide with the fibril, as alternative pathways result
      in misfolding.

PMID- 22995503
TI  - Hydrogen-bonded networks along and bifurcation of the E-pathway in
      quinol:fumarate reductase.
AB  - The E-pathway of transmembrane proton transfer has been demonstrated previously
      to be essential for catalysis by the diheme-containing quinol:fumarate reductase
      (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu-C180 and
      heme b(D) ring C (b(D)-C-) propionate, have been validated experimentally. Here,
      we identify further constituents of the E-pathway by analysis of molecular
      dynamics simulations. The redox state of heme groups has a crucial effect on the
      connectivity patterns of mobile internal water molecules that can transiently
      support proton transfer from the b(D)-C-propionate to Glu-C180. The short H
      bonding paths formed in the reduced states can lead to high proton conduction
      rates and thus provide a plausible explanation for the required opening of the E
      pathway in reduced QFR. We found evidence that the b(D)-C-propionate group is the
      previously postulated branching point connecting proton transfer to the E-pathway
      from the quinol-oxidation site via interactions with the heme b(D) ligand His
      C44. An essential functional role of His-C44 is supported experimentally by site
      directed mutagenesis resulting in its replacement with Glu. Although the H44E
      variant enzyme retains both heme groups, it is unable to catalyze quinol
      oxidation. All results obtained are relevant to the QFR enzymes from the human
      pathogens Campylobacter jejuni and Helicobacter pylori.

PMID- 22995504
TI  - Variational Bayes analysis of a photon-based hidden Markov model for single
      molecule FRET trajectories.
AB  - Single-molecule fluorescence resonance energy transfer (smFRET) measurement is a
      powerful technique for investigating dynamics of biomolecules, for which various
      efforts have been made to overcome significant stochastic noise. Time stamp (TS)
      measurement has been employed experimentally to enrich information within the
      signals, while data analyses such as the hidden Markov model (HMM) have been
      successfully applied to recover the trajectories of molecular state transitions
      from time-binned photon counting signals or images. In this article, we introduce
      the HMM for TS-FRET signals, employing the variational Bayes (VB) inference to
      solve the model, and demonstrate the application of VB-HMM-TS-FRET to simulated
      TS-FRET data. The same analysis using VB-HMM is conducted for other models and
      the previously reported change point detection scheme. The performance is
      compared to other analysis methods or data types and we show that our VB-HMM-TS
      FRET analysis can achieve the best performance and results in the highest time
      resolution. Finally, an smFRET experiment was conducted to observe spontaneous
      branch migration of Holliday-junction DNA. VB-HMM-TS-FRET was successfully
      applied to reconstruct the state transition trajectory with the number of states
      consistent with the nucleotide sequence. The results suggest that a single
      migration process frequently involves rearrangement of multiple basepairs.

PMID- 22995505
TI  - A comparative kinetic and thermodynamic perspective of the sigma-competition
      model in Escherichia coli.
AB  - Transcription is the most fundamental step in gene expression in any living
      organism. Various environmental cues help in the maturation of core RNA
      polymerase (RNAP; alpha(2)betabeta'omega) with different sigma-factors, leading
      to the directed recruitment of RNAP to different promoter DNA sequences. Thus it
      is essential to determine the sigma-factors that affect the preferential
      partitioning of core RNAP among various sigma-actors, and the role of sigma
      switching in transcriptional gene regulation. Further, the macromolecular
      assembly of holo RNAP takes place in an extremely crowded environment within a
      cell, and thus far the kinetics and thermodynamics of this molecular recognition
      process have not been well addressed. In this study we used a site-directed
      bioaffinity immobilization method to evaluate the relative binding affinities of
      three different Escherichia coli sigma-factors to the same core RNAP with
      variations in temperature and ionic strength while emulating the crowded cellular
      milieu. Our data indicate that the interaction of core RNAP-sigma is susceptible
      to changes in external stimuli such as osmolytic and thermal stress, and the
      degree of susceptibility varies among different sigma-factors. This allows for a
      reversible sigma-switching from housekeeping factors to alternate sigma-factors
      when the organism senses a change in its physiological conditions.

PMID- 22995506
TI  - Coarse-graining provides insights on the essential nature of heterogeneity in
      actin filaments.
AB  - Experiments have shown that actin is structurally polymorphic, but knowledge of
      the details of molecular level heterogeneity in both the dynamics of a single
      subunit and the interactions between subunits is still lacking. Here, using
      atomistic molecular dynamics simulations of the actin filament, we identify
      domains of atoms that move in a correlated fashion, quantify interactions between
      these domains using coarse-grained (CG) analysis methods, and perform CG
      simulations to explore the importance of filament heterogeneity. The persistence
      length and torsional stiffness calculated from molecular dynamics simulation data
      agree with experimental values. We additionally observe that distinct actin
      conformations coexist in actin filaments. The filaments also exhibit random twist
      angles that are broadly distributed. CG analysis reveals that interactions
      between equivalent CG pairs vary from one subunit to another. To explore the
      importance of heterogeneity on filament dynamics, we perform CG simulations using
      different methods of parameterization to show that only by including
      heterogeneous interactions can we reproduce the twist angles and related
      properties. Free energy calculations further suggest that in general the actin
      filament is best represented as a set of subunits with differing CG sites and
      interactions, and the incorporating heterogeneity into the CG interactions is
      more important than including that in the CG sites. Our work therefore presents a
      systematic method to explore molecular level detail in this large and complex
      biopolymer.

PMID- 22995507
TI  - Structure-based simulations of the translocation mechanism of the hepatitis C
      virus NS3 helicase along single-stranded nucleic acid.
AB  - The NS3 helicase of Hepatitis C virus is an ATP-fueled molecular motor that can
      translocate along single-stranded (ss) nucleic acid, and unwind double-stranded
      nucleic acids. It makes a promising antiviral target and an important prototype
      system for helicase research. Despite recent progress, the detailed mechanism of
      NS3 helicase remains unknown. In this study, we have combined coarse-grained (CG)
      and atomistic simulations to probe the translocation mechanism of NS3 helicase
      along ssDNA. At the residue level of detail, our CG simulations have captured
      functionally important interdomain motions of NS3 helicase and reproduced single
      base translocation of NS3 helicase along ssDNA in the 3'-5' direction, which is
      in good agreement with experimental data and the inchworm model. By combining the
      CG simulations with residue-specific perturbations to protein-DNA interactions,
      we have identified a number of key residues important to the translocation
      machinery that agree with previous structural and mutational studies.
      Additionally, our atomistic simulations with targeted molecular dynamics have
      corroborated the findings of CG simulations and further revealed key protein-DNA
      hydrogen bonds that break/form during the transitions. This study offers, to our
      knowledge, the most detailed and realistic simulations of translocation mechanism
      of NS3 helicase. The simulation protocol established in this study will be useful
      for designing inhibitors that target the translocation machinery of NS3 helicase,
      and for simulations of a variety of nucleic-acid-based molecular motors.

PMID- 22995508
TI  - Quantitative characterization of local protein solvation to predict solvent
      effects on protein structure.
AB  - Characterization of solvent preferences of proteins is essential to the
      understanding of solvent effects on protein structure and stability. Although it
      is generally believed that solvent preferences at distinct loci of a protein
      surface may differ, quantitative characterization of local protein solvation has
      remained elusive. In this study, we show that local solvation preferences can be
      quantified over the entire protein surface from extended molecular dynamics
      simulations. By subjecting microsecond trajectories of two proteins (lysozyme and
      antibody fragment D1.3) in 4 M glycerol to rigorous statistical analyses, solvent
      preferences of individual protein residues are quantified by local preferential
      interaction coefficients. Local solvent preferences for glycerol vary widely from
      residue to residue and may change as a result of protein side-chain motions that
      are slower than the longest intrinsic solvation timescale of ~10 ns. Differences
      of local solvent preferences between distinct protein side-chain conformations
      predict solvent effects on local protein structure in good agreement with
      experiment. This study extends the application scope of preferential interaction
      theory and enables molecular understanding of solvent effects on protein
      structure through comprehensive characterization of local protein solvation.

PMID- 22995509
TI  - Simulations of HIV capsid protein dimerization reveal the effect of chemistry and
      topography on the mechanism of hydrophobic protein association.
AB  - Recent work has shown that the hydrophobic protein surfaces in aqueous solution
      sit near a drying transition. The tendency for these surfaces to expel water from
      their vicinity leads to self-assembly of macromolecular complexes. In this
      article, we show with a realistic model for a biologically pertinent system how
      this phenomenon appears at the molecular level. We focus on the association of
      the C-terminal domain (CA-C) of the human immunodeficiency virus capsid protein.
      By combining all-atom simulations with specialized sampling techniques, we
      measure the water density distribution during the approach of two CA-C proteins
      as a function of separation and amino acid sequence in the interfacial region.
      The simulations demonstrate that CA-C protein-protein interactions sit at the
      edge of a dewetting transition and that this mesoscopic manifestation of the
      underlying liquid-vapor phase transition can be readily manipulated by biology or
      protein engineering to significantly affect association behavior. Although the
      wild-type protein remains wet until contact, we identify a set of in silico
      mutations, in which three hydrophilic amino acids are replaced with nonpolar
      residues, that leads to dewetting before association. The existence of dewetting
      depends on the size and relative locations of substituted residues separated by
      nanometer length scales, indicating long-range cooperativity and a sensitivity to
      surface topography. These observations identify important details that are
      missing from descriptions of protein association based on buried hydrophobic
      surface area.

PMID- 22995510
TI  - Protein-protein interactions in calcium transport regulation probed by saturation
      transfer electron paramagnetic resonance.
AB  - We have used electron paramagnetic resonance (EPR) to probe the homo- and
      heterooligomeric interactions of reconstituted sarcoplasmic reticulum Ca-ATPase
      (SERCA) and its regulator phospholamban (PLB). SERCA is responsible for restoring
      calcium to the sarcoplasmic reticulum to allow muscle relaxation, whereas PLB
      inhibits cardiac SERCA unless phosphorylated at Ser(16). To determine whether
      changes in protein association play essential roles in regulation, we detected
      the microsecond rotational diffusion of both proteins using saturation transfer
      EPR. Peptide synthesis was used to create a fully functional and monomeric PLB
      mutant with a spin label rigidly coupled to the backbone of the transmembrane
      helix, while SERCA was reacted with a Cys-specific spin label. Saturation
      transfer EPR revealed that sufficiently high lipid/protein ratios minimized self
      association for both proteins. Under these dilute conditions, labeled PLB was
      substantially immobilized after co-reconstitution with unlabeled SERCA,
      reflecting their association to form the regulatory complex. Ser(16)
      phosphorylation slightly increased this immobilization. Complementary
      measurements with labeled SERCA showed no change in mobility after co
      reconstitution with unlabeled PLB, regardless of its phosphorylation state. We
      conclude that phosphorylating monomeric PLB can relieve SERCA inhibition without
      changes in the oligomeric states of these proteins, indicating a structural
      rearrangement within the heterodimeric regulatory complex.

PMID- 22995511
TI  - A spatial model for integrin clustering as a result of feedback between integrin
      activation and integrin binding.
AB  - Integrins are transmembrane adhesion receptors that bind extracellular matrix
      (ECM) proteins and signal bidirectionally to regulate cell adhesion and
      migration. In many cell types, integrins cluster at cell-ECM contacts to create
      the foundation for adhesion complexes that transfer force between the cell and
      the ECM. Even though the temporal and spatial regulation of these integrin
      clusters is essential for cell migration, how cells regulate their formation is
      currently unknown. It has been shown that integrin cluster formation is
      independent of actin stress fiber formation, but requires active (high-affinity)
      integrins, phosphoinositol-4,5-bisphosphate (PIP2), talin, and immobile ECM
      ligand. Based on these observations, we propose a minimal model for initial
      formation of integrin clusters, facilitated by localized activation and binding
      of integrins to ECM ligands as a result of biochemical feedback between integrin
      binding and integrin activation. By employing a diffusion-reaction framework for
      modeling these reactions, we show how spatial organization of bound integrins
      into clusters may be achieved by a local source of active integrins, namely
      protein complexes formed on the cytoplasmic tails of bound integrins. Further, we
      show how such a mechanism can turn small local increases in the concentration of
      active talin or active integrin into integrin clusters via positive feedback. Our
      results suggest that the formation of integrin clusters by the proposed mechanism
      depends on the relationships between production and diffusion of integrin
      activating species, and that changes to the relative rates of these processes may
      affect the resulting properties of integrin clusters.

PMID- 22995512
TI  - The relation of signal transduction to the sensitivity and dynamic range of
      bacterial chemotaxis.
AB  - Complex networks of interacting molecular components of living cells are
      responsible for many important processes, such as signal processing and
      transduction. An important challenge is to understand how the individual
      properties of these molecular interactions and biochemical transformations
      determine the system-level properties of biological functions. Here, we address
      the issue of the accuracy of signal transduction performed by a bacterial
      chemotaxis system. The chemotaxis sensitivity of bacteria to a chemoattractant
      gradient has been measured experimentally from bacterial aggregation in a
      chemoattractant-containing capillary. The observed precision of the chemotaxis
      depended on environmental conditions such as the concentration and molecular
      makeup of the chemoattractant. In a quantitative model, we derived the
      chemotactic response function, which is essential to describing the signal
      transduction process involved in bacterial chemotaxis. In the presence of a
      gradient, an analytical solution is derived that reveals connections between the
      chemotaxis sensitivity and the characteristics of the signaling system, such as
      reaction rates. These biochemical parameters are integrated into two system-level
      parameters: one characterizes the efficiency of gradient sensing, and the other
      is related to the dynamic range of chemotaxis. Thus, our approach explains how a
      particular signal transduction property affects the system-level performance of
      bacterial chemotaxis. We further show that the two parameters can be derived from
      published experimental data from a capillary assay, which successfully
      characterizes the performance of bacterial chemotaxis.

PMID- 22995513
TI  - Mapping of bacterial biofilm local mechanics by magnetic microparticle actuation.
AB  - Most bacteria live in the form of adherent communities forming three-dimensional
      material anchored to artificial or biological surfaces, with profound impact on
      many human activities. Biofilms are recognized as complex systems but their
      physical properties have been mainly studied from a macroscopic perspective. To
      determine biofilm local mechanical properties, reveal their potential
      heterogeneity, and investigate their relation to molecular traits, we have
      developed a seemingly new microrheology approach based on magnetic particle
      infiltration in growing biofilms. Using magnetic tweezers, we achieved what was,
      to our knowledge, the first three-dimensional mapping of the viscoelastic
      parameters on biofilms formed by the bacterium Escherichia coli. We demonstrate
      that its mechanical profile may exhibit elastic compliance values spread over
      three orders of magnitude in a given biofilm. We also prove that heterogeneity
      strongly depends on external conditions such as growth shear stress. Using
      strains genetically engineered to produce well-characterized cell surface
      adhesins, we show that the mechanical profile of biofilm is exquisitely sensitive
      to the expression of different surface appendages such as F pilus or curli. These
      results provide a quantitative view of local mechanical properties within intact
      biofilms and open up an additional avenue for elucidating the emergence and fate
      of the different microenvironments within these living materials.

PMID- 22995514
TI  - Characterization of the adaptation module of the signaling network in bacterial
      chemotaxis by measurement of step responses.
AB  - The bacterial chemotaxis network features robust adaptation implemented by
      negative integral feedback. Here, we show that the adaptation module can be
      characterized by measurement of the response to simple step-addition and removal
      of a chemoattractant. The method does not rely on a particular form of the
      receptor module, and thus can be used to characterize other integral feedback
      networks.

PMID- 22995515
TI  - Upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7
      by miR-29 repression mediates vascular smooth muscle calcification.
AB  - OBJECTIVE: Vascular calcification significantly increases cardiovascular
      morbidity and mortality. We recently reported that the deficiency of cartilage
      oligomeric matrix protein (COMP) leads to vascular mineralization. We
      characterized the COMP-degrading metalloproteinase, a disintegrin and
      metalloproteinase with thrombospondin motifs-7 (ADAMTS-7). Here, we tested
      whether ADAMTS-7 facilitates vascular calcification. METHODS AND RESULTS: ADAMTS
      7 expression was markedly upregulated in calcifying rat vascular smooth muscle
      cells (VSMCs) in vitro, calcified arteries of rats with chronic renal failure in
      vivo, and radial arteries of uraemic patients. Silencing of ADAMTS-7 markedly
      reduced COMP degradation and ameliorated VSMC calcification, whereas ectopic
      expression of ADAMTS-7 greatly enhanced COMP degradation and exacerbated
      mineralization. The transcriptional activity of ADAMTS-7 promoter was not altered
      by high phosphate. We used bioinformatics and quantitative polymerase chain
      reaction analysis to demonstrate that high-phosphate upregulated ADAMTS-7 mRNA
      and protein via miR-29a/b repression, which directly targeted the 3' untranslated
      region of ADAMTS-7 in VSMCs. MicroRNA (MiR)-29a/b mimic markedly inhibited but
      miR-29a/b inhibitor greatly enhanced high-phosphate-induced ADAMTS-7 expression,
      COMP degradation, and subsequent VSMC calcification. ADAMTS-7 silencing
      significantly diminished miR-29a/b repression-exaggerated VSMC calcification.
      CONCLUSIONS: Our data reveal a novel mechanism by which ADAMTS-7 upregulation by
      miR-29a/b repression mediates vascular calcification, which may shed light on
      preventing cardiovascular morbidity and mortality.

PMID- 22995516
TI  - The role of Rac1 in glycoprotein Ib-IX-mediated signal transduction and integrin
      activation.
AB  - OBJECTIVE: The platelet receptor for von Willebrand factor, the glycoprotein Ib
      IX (GPIb-IX) complex, mediates platelet adhesion at sites of vascular injury and
      transmits signals leading to platelet activation. von Willebrand factor/GPIb-IX
      interaction sequentially activates the Src family kinase Lyn (SFK),
      phosphoinositide 3-kinase (PI3K), and Akt, leading to activation of integrin
      alpha(IIb)beta(3) and integrin-dependent stable platelet adhesion and
      aggregation. It remains unclear how Lyn activates the PI3K/Akt pathway after
      ligand binding to GPIb-IX. METHODS AND RESULTS: Using platelet-specific Rac1(-/-)
      mice and the Rac1 inhibitor NSC23766, we examined the role of Rac1 in GPIb-IX
      dependent platelet activation. Rac1(-/-) mouse platelets and NSC23766-treated
      human platelets were defective in GPIb-dependent stable adhesion to von
      Willebrand factor under shear stress, integrin activation, thromboxane A(2)
      synthesis, and platelet aggregation. Interestingly, GPIb-induced activation of
      Rac1 and the guanine nucleotide exchange factor for Rac1, Vav, was abolished in
      both Lyn(-/-) and SFK inhibitor-treated platelets but was unaffected by the PI3K
      inhibitor LY294002, indicating that Lyn mediates activation of Vav and Rac1
      independently of PI3K. Furthermore, GPIb-induced activation of Akt was abolished
      in Rac1-deficient platelets, suggesting that Rac1 is upstream of the PI3K/Akt
      pathway. CONCLUSIONS: A Lyn-Vav-Rac1-PI3K-Akt pathway mediates von Willebrand
      factor-induced activation of integrin alpha(IIb)beta(3) to promote GPIb-IX
      dependent platelet activation.

PMID- 22995517
TI  - Genetic and pharmacological inhibition of dimethylarginine dimethylaminohydrolase
      1 is protective in endotoxic shock.
AB  - OBJECTIVE: The overproduction of vascular NO contributes toward the circulatory
      collapse observed in patients with septic shock. Dimethylarginine
      dimethylaminohydrolase (DDAH), which has 2 isoforms, metabolizes asymmetrically
      methylated arginines (asymmetric mono- or di-methylarginine), endogenously
      produced NO synthase inhibitors. We wished to investigate whether reducing DDAH1
      activity, using genetic and pharmacological approaches, is protective during
      lipopolysaccharide-induced endotoxic shock. METHODS AND RESULTS: Experiments were
      conducted in DDAH1 heterozygous knockout mice (DDAH1(+/-)) or naive rats treated
      with a synthetic pharmacological DDAH inhibitor (L-257). We demonstrate for the
      first time that L-257 is DDAH1 selective using recombinant human DDAH proteins.
      DDAH1 mRNA was expressed in aortic but not macrophage cDNA, and consistent with
      this expression profile, L-257 selectively inhibited NO production from
      lipopolysaccharide-treated aorta but not macrophages, in culture. Conscious and
      anesthetized cardiovascular hemodynamics were monitored using implanted
      radiotelemetry devices or invasive catheters, respectively. Lipopolysaccharide
      was administered intravenously to model endotoxemia, and all animals presented
      with circulatory shock. DDAH1(+/-) mice or L-257-treated rats displayed
      attenuation in the rate of developed hypotension compared with wild-type
      littermates or vehicle control animals, respectively. CONCLUSIONS:
      Pharmacological and genetic reduction of DDAH1 activity is protective against the
      vascular changes observed during endotoxic shock.

PMID- 22995518
TI  - Apelin/APJ signaling is a critical regulator of statin effects in vascular
      endothelial cells--brief report.
AB  - OBJECTIVE: The endothelial response elicited by the G-protein-coupled receptor
      pathway involving apelin and APJ predicts an overall vasoprotective effect. As a
      number of downstream endothelial targets of apelin/APJ signaling are also known
      to be targeted by statins (3-hydroxy-3-methyl-glutaryl [HMG]-CoA reductase
      inhibitors) as potential mediators of their known pleiotropic effects, we
      evaluated for the involvement of apelin/APJ signaling in statin endothelial
      effects. METHODS AND RESULTS: We found that disruption of apelin/APJ signaling in
      endothelial cells leads to significantly decreased expression of Kruppel-like
      factor 2, endothelial nitric oxide synthase, and thrombomodulin. We found that
      statin-mediated induction of Kruppel-like factor 2, endothelial nitric oxide
      synthase, and thrombomodulin expression, as well as inhibition of monocyte
      endothelial adhesion, was abrogated by concurrent apelin knockdown. Moreover, we
      found that statins can transcriptionally regulate APJ in a Kruppel-like factor 2
      dependent manner, demonstrating the presence of a positive-feedback loop.
      CONCLUSIONS: Our findings provide a novel mechanism by which the apelin/APJ
      pathway serves as a critical intermediary that links statin to its pleiotropic
      effects in regulating endothelial gene targets and function.

PMID- 22995519
TI  - Endogenous IRAK-M attenuates postinfarction remodeling through effects on
      macrophages and fibroblasts.
AB  - OBJECTIVE: Effective postinfarction repair requires timely suppression of innate
      immune signals to prevent the catastrophic consequences of uncontrolled
      inflammation on cardiac geometry and function. In macrophages, interleukin-1
      receptor-associated kinase (IRAK)-M acts as a functional decoy preventing
      uncontrolled toll-like receptor /interleukin-1-mediated responses. Our study
      investigates the role of IRAK-M as a negative regulator of the postinfarction
      inflammatory response and as a modulator of cardiac remodeling. METHODS AND
      RESULTS: In wild-type mouse infarcts IRAK-M was upregulated in infiltrating
      macrophages and fibroblasts exhibiting a biphasic response. When compared with
      wild-type animals, infarcted IRAK-M(-/-) mice had enhanced adverse remodeling and
      worse systolic dysfunction; however, acute infarct size was comparable between
      groups. Adverse remodeling in IRAK-M(-/-) animals was associated with enhanced
      myocardial inflammation and protease activation. The protective actions of IRAK-M
      involved phenotypic modulation of macrophages and fibroblasts. IRAK-M(-/-)
      infarcts showed increased infiltration with proinflammatory CD11b+/Ly6C(hi)
      monocytes; leukocytes harvested from IRAK-M-null infarcts exhibited accentuated
      cytokine expression. In vitro, IRAK-M expression was upregulated in cytokine
      stimulated murine cardiac fibroblasts and suppressed their matrix-degrading
      properties without affecting their inflammatory activity. CONCLUSIONS: Endogenous
      IRAK-M attenuates adverse postinfarction remodeling suppressing leukocyte
      inflammatory activity, while inhibiting fibroblast-mediated matrix degradation.

PMID- 22995520
TI  - TLR 2 induces vascular smooth muscle cell migration through cAMP response element
      binding protein-mediated interleukin-6 production.
AB  - OBJECTIVE: Migration of vascular smooth muscle cells (VSMCs) from the media into
      intima contributes to the development of atherosclerosis. Gene deletion
      experiments implicate a role for toll-like receptor 2 (TLR2) in atherogenesis.
      However, the underlying mechanisms remain unclear. We postulate that TLR2
      promotes VSMC migration by enhancing interleukin (IL)-6 production. METHODS AND
      RESULTS: Migration assays revealed that TLR2 agonists promoted VSMC migration but
      not cell proliferation or viability. TLR2 deficiency or inhibition of TLR2
      signaling with anti-TLR2 antibody suppressed TLR2 agonist-induced VSMC migration
      and IL-6 production, which was mediated via p38 mitogen-associated protein kinase
      and extracellular signal-regulated kinase 1/2 signaling pathways. Neutralizing
      anti-IL-6 antibodies impaired TLR2-mediated VSMC migration and formation of
      filamentous actin fiber and lamellipodia. Blockade of p38 mitogen-associated
      protein kinase or extracellular signal-regulated kinase 1/2 activation inhibited
      TLR2 agonist pam3CSK4-induced phosphorylation of cAMP response element-binding
      protein, which regulates IL-6 promoter activity through the cAMP response element
      site. Moreover, cAMP response element-binding protein small interfering RNA
      inhibited pam3CSK4-induced IL-6 production and VSMC migration. Additionally, Rac1
      small interfering RNA inhibited pam3CSK4-induced VSMC migration but not IL-6
      production. CONCLUSIONS: Our results suggest that on ligand binding, TLR2
      activates p38 mitogen-associated protein kinase and extracellular signal
      regulated kinase 1/2 signaling in VSMCs. These signaling pathways act in concert
      to activate cAMP response element-binding protein and subsequent IL-6 production,
      which in turn promotes VSMC migration via Rac1-mediated actin cytoskeletal
      reorganization.

PMID- 22995522
TI  - White adipose tissue apolipoprotein C-I secretion in relation to delayed plasma
      clearance of dietary fat in humans.
AB  - OBJECTIVE: White adipose tissue (WAT) dysfunction is characterized by delayed
      clearance of dietary triglyceride-rich lipoproteins (TRL). We reported that
      apolipoprotein (apo) C-I, a transferable apolipoprotein that inhibits lipoprotein
      lipase activity when bound to TRL, was produced by a human adipocyte model. Thus,
      we aimed to determine whether increased WAT apoC-I secretion is related to
      delayed dietary fat clearance in humans. METHODS AND RESULTS: After the ingestion
      of a (13)C-triolein-labeled high-fat meal, postmenopausal obese women with high
      fasting WAT apoC-I secretion (median >0.81 MUmol/L per g/4 hours, n=9) had
      delayed postprandial plasma clearance of (13)C-triglyceride and (13)C
      nonesterified fatty acids over 6 hours compared with controls. WAT apoC-I
      secretion over 4 hours correlated with fasting total and non-high-density
      lipoprotein apoC-I but not with high-density lipoprotein apoC-I and was the
      primary predictor of 4-hour postprandial increases in TRL apoC-I. Correction for
      TRL apoC-I eliminated the association of WAT apoC-I with 6-hour area under the
      curve of plasma (13)C-triglyceride; correction for insulin sensitivity or
      inflammation did not. Finally, in addition to apoC-I, WAT secreted considerable
      amount of apoC-II, apoC-III, and apoE over 24 hours; however, only WAT apoC-I
      secretion was associated with 6-hour area under the curve of plasma (13)C
      triglyceride. CONCLUSIONS: Increased WAT apoC-I secretion in obese women is
      associated with delayed postprandial dietary fat clearance mediated by increased
      TRL apoC-I. Thus, we hypothesize that reducing WAT apoC-I secretion ameliorates
      WAT dysfunction and associated cardiometabolic risks in humans.

PMID- 22995521
TI  - Trafficking of endogenous smooth muscle cell cholesterol: a role for serum
      amyloid A and interleukin-1beta.
AB  - OBJECTIVE: Intracellular cholesterol distribution impacts cell function; however,
      processes influencing endogenous cholesterol trafficking remain largely unknown.
      Atherosclerosis is associated with vascular inflammation and these studies
      address the role of inflammatory mediators on smooth muscle cell cholesterol
      trafficking. METHODS AND RESULTS: Interestingly, in the absence of an exogenous
      cholesterol source, serum amyloid A increased [(14)C] oleic acid incorporation
      into cholesteryl ester in rat smooth muscle cells, suggesting endogenous
      cholesterol trafficking to the endoplasmic reticulum. [(3)H] cholesteryl ester
      accumulated in cells prelabeled with [(3)H] cholesterol, confirming that serum
      amyloid A mediated the movement of endogenous cholesterol. Cholesterol movement
      was dependent upon functional endolysosomes. The cholesterol oxidase-sensitive
      pool of cholesterol decreased in serum amyloid A-treated cells. Furthermore, the
      mechanism whereby serum amyloid A induced cholesterol trafficking was determined
      to be via activation of expression of secretory phospholipase A(2), group IIA
      (sPLA(2)) and sPLA(2)-dependent activation of sphingomyelinase. Interestingly,
      although neither tumor necrosis factor-alpha nor interferon-gamma induced
      cholesterol trafficking, interleukin-1beta induced [(14)C] cholesteryl ester
      accumulation that was also dependent upon sPLA(2) and sphingomyelinase
      activities. Serum amyloid A activates smooth muscle cell interleukin-1beta
      expression, and although the interleukin-1-receptor antagonist inhibited the
      interleukin-1beta-induced cholesterol trafficking, it had no effect on the
      movement of cholesterol mediated by serum amyloid A. CONCLUSIONS: These data
      support a role for inflammation in endogenous smooth muscle cell cholesterol
      trafficking from the plasma membrane to the endoplasmic reticulum.

PMID- 22995523
TI  - Atorvastatin delays murine platelet activation in vivo even in the absence of
      endothelial NO synthase.
AB  - OBJECTIVE: Statins decrease mortality in patients with vascular disorders, and
      evidence for the pleiotropic effects of statins is accumulating. Statins enhance
      endothelial NO synthase (eNOS) expression, thereby attenuating platelet
      activation and thrombus formation. Our goal was to determine whether statins have
      eNOS-independent effects on platelet activation. METHODS AND RESULTS: Wild-type
      and eNOS-deficient mice were given a 14-day course of oral atorvastatin, and
      platelet activation was evaluated in vitro and in vivo. Whereas in wild-type mice
      atorvastatin inhibited platelet activation in vitro in response to numerous
      agonists, in eNOS-deficient mice, atorvastatin inhibited only thrombin-induced
      and protease-activated receptor 4 agonist peptide-induced platelet activation.
      Consistent with an eNOS-independent effect, atorvastatin inhibited platelet
      activation in vivo in both wild-type and eNOS-deficient mice. CONCLUSIONS:
      Atorvastatin inhibits platelet activation via eNOS-dependent and eNOS-independent
      mechanisms with the latter restricted to protease-activated receptor 4-induced
      activation downstream to the receptor.

PMID- 22995525
TI  - Characterization of a 32 MUm diameter carbon fiber electrode for in vivo fast
      scan cyclic voltammetry.
AB  - Carbon fiber electrodes (CFE) are commonly used for in vivo detection of
      catecholamines due to their excellent electrochemical properties and
      biocompatibility. Fast-scan cyclic voltammetry (FSCV) combined with CFEs permits
      the detection of catecholamines such as dopamine (DA) with high specificity and
      reliability. However, advances in neuroscience constantly demand sensors with
      greater sensitivities and selectivities. This study investigated an untreated CFE
      of 32 MUm diameter and 300 MUm exposed length for detection of DA using FSCV.
      Despite the larger area of the working electrode, we observed only a small
      increase in the background current in comparison with the commonly used CFE of 7
      MUm diameter and 100 MUm exposed length. The sensitivity of the 32 MUm CFE was 9
      times greater than that of the 7 MUm CFE. These larger electrodes exhibited good
      linearity and a 6 fold higher signal-to-noise ratio than 7 MUm CFEs in vitro. The
      32 MUm CFE showed significantly better selectivity for DA in preference to 3,4
      dihydroxyphenylacetic acid than the 7 MUm CFE and similar selectivity to the 7
      MUm CFE for ascorbic and homovanillic acid. The electrodes displayed good
      temporal resolution and electrochemical stability in both in vitro and in vivo
      tests.

PMID- 22995526
TI  - [Recommendations for the clinical use of motor evoked potentials in multiple
      sclerosis].
AB  - OBJECTIVE: To establish clinical guidelines for the clinical use and
      interpretation of motor evoked potentials (MEP) in diagnosing and monitoring
      patients with multiple sclerosis (MS). Recommendations for MEP use and
      interpretation will help us rationalise and optimise resources used in MS patient
      diagnosis and follow up. METHOD: We completed an extensive literature review and
      pooled our own data to produce a consensus statement with recommendations for the
      clinical use of MEPs in the study of MS. RESULTS: MEPs, in addition to spinal and
      cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients
      whose disease initially presents as spinal cord syndrome and those with non
      specific brain MRI findings, or a normal brain MRI and clinical signs of MS.
      CONCLUSIONS: Whenever possible, a multimodal evoked potential study should be
      performed on patients with suspected MS in order to demonstrate involvement of
      the motor pathway which supports a diagnosis of dissemination in space.

PMID- 22995524
TI  - Inflammation modulates murine venous thrombosis resolution in vivo: assessment by
      multimodal fluorescence molecular imaging.
AB  - OBJECTIVE: Assessment of thrombus inflammation in vivo could provide new insights
      into deep vein thrombosis (DVT) resolution. Here, we develop and evaluate 2
      integrated fluorescence molecular-structural imaging strategies to quantify DVT
      related inflammation and architecture and to assess the effect of thrombus
      inflammation on subsequent DVT resolution in vivo. METHODS AND RESULTS: Murine
      DVT were created with topical 5% FeCl(3) application to thigh or jugular veins
      (n=35). On day 3, mice received macrophage and matrix metalloproteinase activity
      fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation
      and architecture was performed using confocal fluorescence intravital microscopy.
      Day 4 analyses showed robust relationships among in vivo thrombus macrophages,
      matrix metalloproteinase activity, and fluorescein isothiocyanate-dextran
      deposition (r>0.70; P<0.01). In a serial 2-time point study, mice with DVT
      underwent intravital microscopy at day 4 and day 6. Analyses revealed that the
      intensity of thrombus inflammation at day 4 predicted the magnitude of DVT
      resolution at day 6 (P<0.05). In a second approach, noninvasive fluorescence
      molecular tomography-computed tomography was used and detected macrophages within
      jugular DVT (P<0.05 versus sham controls). CONCLUSIONS: Integrated fluorescence
      molecular-structural imaging demonstrates that the DVT-induced inflammatory
      response can be readily assessed in vivo and can inform the magnitude of thrombus
      resolution.

PMID- 22995527
TI  - The costs of stroke in Spain by aetiology: the CONOCES study protocol.
AB  - INTRODUCTION: Patients with stroke associated with non-valvular atrial
      fibrillation (NVAF) are a specific group, and their disease has a considerable
      social and economic impact. The primary objective of the CONOCES study, the
      protocol of which is presented here, is to compare the costs of stroke in NVAF
      patients to those of patients without NVAF in Spanish stroke units from a
      societal perspective. MATERIALS AND METHODS: CONOCES is an epidemiological,
      observational, naturalistic, prospective, multicentre study of the cost of the
      illness in a sample of patients who have suffered a stroke and were admitted to a
      Spanish stroke unit. During a 12-month follow-up period, we record
      sociodemographic and clinical variables, score on the NIH stroke scale, level of
      disability, degree of functional dependency according to the modified Rankin
      scale, and use of healthcare resources (hospitalisation at the time of the first
      episode, readmissions, outpatient rehabilitation, orthotic and/or prosthetic
      material, medication for secondary prevention, medical check-ups, nursing care
      and formal social care services). Estimated monthly income, lost work
      productivity and health-related quality of life measured with the generic EQ-5D
      questionnaire are also recorded. We also administer a direct interview to the
      caregiver to determine loss of productivity, informal care, and caregiver burden.
      RESULTS AND CONCLUSIONS: The CONOCES study will provide more in-depth information
      about the economic and clinical impact of stroke according to whether or not it
      is associated with NVAF.

PMID- 22995528
TI  - Behaviour problems in adolescents with cardiac disease: an exploratory study in a
      paediatric cardiology outpatient clinic.
AB  - AIMS: To assess behavioural problems in adolescents with congenital and acquired
      heart disease in comparison with healthy controls. The perception of behavioural
      problems by the patients' parents was also assessed and compared. METHODS: A
      cross-sectional study was carried out in 130 adolescents with congenital and
      acquired heart disease and 246 healthy controls. The second part of the Youth
      Self-Report was applied to the patients and controls, and the Child Behavior
      Checklist to the patients' parents. RESULTS: Male patients showed significantly
      fewer behavioural problems compared with male controls. No significant difference
      was found in the female gender. Healthy male adolescents scored significantly
      higher in the Internalising, Externalising, and in the Total Problems scales.
      Patients scored significantly higher only on the Social Problems subscale. Female
      patients in middle and late adolescence and male patients in early adolescence
      displayed more problems. No significant difference was found between the
      diagnostic groups. Operated patients did not differ from the non-operated ones.
      Patients scored significantly lower than did their parents. CONCLUSIONS: Male
      adolescents with cardiac disease reported fewer behavioural problems when
      compared with healthy controls, but no difference was observed in the female
      gender. Patients also reported fewer behavioural problems than did their parents.
      Adolescents with cardiac disease scored higher than did controls only on the
      Social Problems subscale. Analysing the patients' behavioural profile, female
      patients in middle and late adolescence and male patients in early adolescence
      were the most problematic ones. No difference was observed between the diagnostic
      groups, nor between operated and non-operated patients.

PMID- 22995529
TI  - Inflammatory, immune and lipid transportation proteins are differentially
      expressed in spontaneous and proximal deep vein thrombosis patients.
AB  - INTRODUCTION: Deep vein thrombosis (DVT) is a multi-causal disease associated
      with high morbidity and mortality due to complications, and 25% of patients
      present recurrence within 5 years. The identification of factors involved with
      DVT can help in the management of patients, prevention of recurrence and in the
      development of new therapies. The evaluation of plasma components using
      proteomics potentially provides a window into the individual's state of health.
      We analyzed the protein profile of plasma samples from 3 DVT patients and
      compared results to those obtained from 1 sibling and 1 neighbor of each patient.
      These patients were selected as they presented a personal and family history of
      spontaneous and recurrent episodes of proximal DVT. MATERIAL AND METHODS: Albumin
      was removed using Affi-Gel Blue Gel, and the proteins were alkylated, reduced,
      precipitated and hydrolyzed. The peptides were fractionated by SCX
      chromatography, the 7 fractions obtained were directed to the ESI Q-TOF Premier
      mass spectrometer. Protein search was performed using the Mascot engine against
      the IPI human database. RESULTS: Proteins that were statistically overexpressed
      in DVT patients included C4-A plasma protease, C1 inter-alpha-trypsin inhibitor,
      heavy chain H inhibitor and serum amyloid A. Proteins that were statistically
      reduced in DVT patients included alpha-2-HS-glycoprotein, isoform 2 of inter
      alpha-trypsin inhibitor heavy chain H4 and apolipoprotein A-IV. CONCLUSIONS: The
      evaluation of plasma from patients with spontaneous DVT allows the identification
      of differently expressed proteins when compared to controls; this expression may
      be of pathological importance for immune and inflammatory processes in DVT.

PMID- 22995530
TI  - Thrombosis in VonWillebrand disease.
AB  - OBJECTIVE: To date, only a few case studies have reported occurrence of
      thrombosis in patients with VonWillebrand disease (VWD). No studies have looked
      at its incidence in this patient population. The aim of this study was to test
      our hypothesis that decreased VonWillebrand factor (VWF) levels confer a
      protective effect on arterial and venous thrombosis. METHODS: This is a
      retrospective cohort study including patients (n=350) with the ICD-9 code of VWD
      who were identified from our hospital database over a period of 25 years, out of
      which 198 patients were included in the final sample. A parallel control sample
      without VWD matched for age, sex, hypertension, hyperlipidemia, atrial
      fibrillation and diabetes mellitus was also obtained from the hospital database.
      The primary outcomes were incidence of diagnosis of symptomatic arterial and
      venous thrombosis. The results were computed using multivariate conditional
      logistic regression analysis and proportions were compared using McNemer's Chi -
      square test. RESULTS: Out of 198 patients (mean age 44.2 +/- 17.5, women 72%)
      with VWD, 170 (86%) were VWD type 1, 21 (10%) were type 2 and 7 (3%) were type 3.
      VWD was found to be an independent protective predictor from arterial thrombosis
      (OR 0.28, 95% CI 0.14-0.54, p<0.0001), more so in CAD (OR 0.28, 95% CI 0.12-0.64,
      p=0.002) than in CVD (OR 0.28, 95% CI 0.10-0.77, p=0.01). However this was not
      the case in venous thrombosis (p=0.42). CONCLUSION: In a population of relatively
      younger individuals with VWD, our study suggests a reduced incidence of arterial
      thrombosis but not of venous thrombosis. This brings up the possibility that
      there could be other pathways or factors involved in arterial and venous
      thrombosis. To our knowledge, this is the first large observational study that
      has provided insight into the thrombotic disease in this group of patients.

PMID- 22995531
TI  - Efficacy of delayed thromboprophylaxis with dabigatran: pooled analysis.
AB  - INTRODUCTION: Oral thromboprophylaxis with dabigatran etexilate should be
      initiated as a half dose 1 to 4h after major orthopaedic surgery. However, a
      delay in dosing could occur for clinical or logistical reasons. A post hoc
      analysis was carried out to determine if patients with delayed dosing received
      adequate anticoagulation. PATIENTS AND METHODS: The RE-MODELTM and RE-NOVATE(r)
      trials compared 220 mg and 150 mg dabigatran etexilate with 40 mg enoxaparin.
      Pooled data for major venous thromboembolism (VTE) and VTE-related mortality
      (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant
      bleeding events, and all bleeding events (safety outcomes) were analysed. Results
      in patients with dosing delayed more than 4h postsurgery were compared with those
      of patients without a delay. RESULTS: Onset of treatment was delayed in 724
      (13.3%) of 5425 patients. Efficacy of 220 mg dabigatran etexilate was similar in
      patients without delayed dosing, patients with a delay and patients with a delay
      until the day after surgery. Rates of efficacy outcome were higher in patients on
      150 mg dabigatran etexilate, but more than 80% of these patients were
      undertreated based on age or renal clearance status. Some differences in bleeding
      events were seen among patient groups by treatment arm. CONCLUSION: Dabigatran
      etexilate thromboprophylaxis should be initiated 1 to 4h postsurgery. Results
      from our post-hoc analysis indicate that no loss of efficacy appears to occur if
      initiation of dabigatran etexilate 220 mg needs to be delayed.

PMID- 22995532
TI  - Shear-induced platelet aggregation in aspirin-treated patients: initial
      experience with the novel PlaCor PRT device.
AB  - INTRODUCTION: Whole blood platelet function testing is widely used to evaluate
      the effect of antiplatelet agents. Most platelet function tests employ agonists
      to evaluate drug-specific platelet-activating pathways. Shear-based tests may
      better reflect physiological conditions in vivo compared with agonist-based
      tests. The novel PlaCor PRT provides a global platelet reactivity test based on
      shear-induced platelet aggregation. We evaluated the PlaCor PRT and its agreement
      with two widely used platelet function tests. MATERIALS AND METHODS: We evaluated
      platelet function in 85 patients with angiographically verified coronary artery
      disease on aspirin mono-therapy. Blood sampling was performed one hour after
      aspirin ingestion. The following platelet function tests were used: PlaCor PRT,
      multiple electrode aggregometry (Multiplate, agonists: arachidonic acid 1.0
      mmol/L and collagen 1.0 MUg/mL) and VerifyNow Aspirin. RESULTS: PlaCor PRT
      results correlated significantly with multiple electrode aggregometry induced by
      arachidonic acid (r=-0.38, p<0.001), but not with multiple electrode aggregometry
      induced by collagen (r=-0.05, p=0.64) or with turbidimetric aggregometry
      performed with VerifyNow Aspirin (r=-0.13, p=0.23). There was a strong
      correlation between PlaCor PRT results and platelet count (r=-0.60, p<0.0001),
      whereas no correlation with haematocrit or von Willebrand factor antigen was
      found. A relatively large number of instrument errors occurred with the PlaCor
      PRT device in this initial testing. CONCLUSIONS: PlaCor PRT is a portable, rapid
      and user-friendly point-of-care test. It shows a modest agreement with comparable
      tests, and results depend considerably on platelet count. Further validation of
      the PlaCor PRT is warranted.

PMID- 22995533
TI  - Arginine exposure alters ectonucleotidase activities and morphology of zebrafish
      larvae (Danio rerio).
AB  - Hyperargininemia is an inborn error of metabolism (IEM) characterized by tissue
      accumulation of arginine (Arg). Mental retardation and other neurological
      features are common symptoms in hyperargininemic patients. Considering purinergic
      signaling has a crucial role from the early stages of development and underlying
      mechanisms of this disease are poorly established, we investigated the effect of
      Arg administration on locomotor activity, morphological alterations, and
      extracellular nucleotide hydrolysis in larvae and adult zebrafish. We showed that
      0.1 mM Arg was unable to promote changes in locomotor activity. In addition, 7
      day-post-fertilization (dpf) larvae treated with Arg demonstrated a decreased
      body size. Arg exposure (0.1 mM) promoted an increase in ATP, ADP, and AMP
      hydrolysis when compared to control group. These findings demonstrated that Arg
      might affect morphological parameters and ectonucleotidase activities in
      zebrafish larvae, suggesting that purinergic system is a target for neurotoxic
      effects induced by Arg.

PMID- 22995534
TI  - A cost-effective method for Illumina small RNA-Seq library preparation using T4
      RNA ligase 1 adenylated adapters.
AB  - BACKGROUND: Deep sequencing is a powerful tool for novel small RNA discovery.
      Illumina small RNA sequencing library preparation requires a pre-adenylated 3'
      end adapter containing a 5',5'-adenyl pyrophosphoryl moiety. In the absence of
      ATP, this adapter can be ligated to the 3' hydroxyl group of small RNA, while RNA
      self-ligation and concatenation are repressed. Pre-adenylated adapters are one of
      the most essential and costly components required for library preparation, and
      few are commercially available. RESULTS: We demonstrate that DNA oligo with 5'
      phosphate and 3' amine groups can be enzymatically adenylated by T4 RNA ligase 1
      to generate customized pre-adenylated adapters. We have constructed and sequenced
      a small RNA library for tomato (Solanum lycopersicum) using the T4 RNA ligase 1
      adenylated adapter. CONCLUSION: We provide an efficient and low-cost method for
      small RNA sequencing library preparation, which takes two days to complete and
      costs around $20 per library. This protocol has been tested in several plant
      species for small RNA sequencing including sweet potato, pepper, watermelon, and
      cowpea, and could be readily applied to any RNA samples.

PMID- 22995535
TI  - Innovation in weight loss programs: a 3-dimensional virtual-world approach.
AB  - BACKGROUND: The rising trend in obesity calls for innovative weight loss
      programs. While behavioral-based face-to-face programs have proven to be the most
      effective, they are expensive and often inaccessible. Internet or Web-based
      weight loss programs have expanded reach but may lack qualities critical to
      weight loss and maintenance such as human interaction, social support, and
      engagement. In contrast to Web technologies, virtual reality technologies offer
      unique affordances as a behavioral intervention by directly supporting engagement
      and active learning. OBJECTIVE: To explore the effectiveness of a virtual-world
      weight loss program relative to weight loss and behavior change. METHODS: We
      collected data from overweight people (N = 54) participating in a face-to-face or
      a virtual-world weight loss program. Weight, body mass index (BMI), percentage
      weight change, and health behaviors (ie, weight loss self-efficacy, physical
      activity self-efficacy, self-reported physical activity, and fruit and vegetable
      consumption) were assessed before and after the 12-week program. Repeated
      measures analysis was used to detect differences between groups and across time.
      RESULTS: A total of 54 participants with a BMI of 32 (SD 6.05) kg/m(2)enrolled in
      the study, with a 13% dropout rate for each group (virtual world group: 5/38;
      face-to-face group: 3/24). Both groups lost a significant amount of weight
      (virtual world: 3.9 kg, P < .001; face-to-face: 2.8 kg, P = .002); however, no
      significant differences between groups were detected (P = .29). Compared with
      baseline, the virtual-world group lost an average of 4.2%, with 33% (11/33) of
      the participants losing a clinically significant (>=5%) amount of baseline
      weight. The face-to-face group lost an average of 3.0% of their baseline weight,
      with 29% (6/21) losing a clinically significant amount. We detected a significant
      group * time interaction for moderate (P = .006) and vigorous physical activity
      (P = .008), physical activity self-efficacy (P = .04), fruit and vegetable
      consumption (P = .007), and weight loss self-efficacy (P < .001). Post hoc paired
      t tests indicated significant improvements across all of the variables for the
      virtual-world group. CONCLUSIONS: Overall, these results offer positive early
      evidence that a virtual-world-based weight loss program can be as effective as a
      face-to-face one relative to biometric changes. In addition, our results suggest
      that a virtual world may be a more effective platform to influence meaningful
      behavioral changes and improve self-efficacy.

PMID- 22995536
TI  - Our time: a call to save preventable death from cardiovascular disease (heart
      disease and stroke).

PMID- 22995537
TI  - When can a woman have an intrauterine device inserted? A systematic review.
AB  - BACKGROUND: Intrauterine device (IUD) insertion during menses may be viewed as
      preferable by some providers, as it provides reassurance that the woman is not
      pregnant. However, this practice may result in unnecessary inconvenience and cost
      to women. The objective of this systematic review is to evaluate the evidence for
      the effect of inserting IUDs on different days of the menstrual cycle on
      contraceptive continuation, effectiveness and safety. STUDY DESIGN: We searched
      the MEDLINE database for peer-reviewed articles published in any language from
      database inception through March 2012 concerning the effect of inserting copper
      IUDs (Cu-IUD) or levonorgestrel-releasing IUDs (LNG-IUDs) on different days of
      the menstrual cycle on contraceptive continuation, effectiveness, and safety. The
      quality of each individual piece of evidence was assessed using the United States
      Preventive Services Task Force grading system. RESULTS: We identified eight
      articles that met the criteria for review. Each study examined the Cu-IUD; no
      studies were identified that examined the LNG-IUD. Overall, these studies suggest
      that timing of Cu-IUD insertion has little effect on longer term outcomes (rates
      of continuation, removal, expulsion, or pregnancy) or on shorter term outcomes
      (pain at insertion, bleeding at insertion, immediate expulsion). Specifically,
      there was no evidence to suggest that outcomes were better when Cu-IUD insertions
      were performed during menses. Limitations of the studies include small sample
      sizes for insertions performed during later days of the menstrual cycle and non
      randomized assignment to timing of insertion. CONCLUSIONS: There is fair evidence
      (body of evidence grading: II-2, fair) indicating that timing of Cu-IUD insertion
      has little effect on contraceptive continuation, effectiveness or safety.

PMID- 22995538
TI  - When can a woman resume or initiate contraception after taking emergency
      contraceptive pills? A systematic review.
AB  - BACKGROUND: Hormonal emergency contraception can postpone ovulation, making a
      woman vulnerable to pregnancy later in the same cycle. However, concern exists as
      to whether concurrently administered emergency contraception pills (ECP) and
      other hormonal methods of contraception may affect the effectiveness of both
      medications. STUDY DESIGN: A systematic review of the literature using PubMed and
      the Cochrane databases was performed to identify articles concerning the
      resumption or initiation of regular contraception within the same cycle as ECP
      use. We searched for articles in any language, published between 1980 and April
      2012 and included all methods of emergency contraception pills available in the
      USA. RESULTS: The search strategy identified 184 articles in the PubMed and
      Cochrane databases, of which none met inclusion criteria. CONCLUSION: The drug
      manufacturer advises continuation or initiation of routine contraception as soon
      as possible after use of ulipristal acetate, with concomitant use of a reliable
      barrier method until next menses. However, a theoretical concern exists that
      given ulipristal acetate's function as a selective progesterone receptor
      modulator, coadministration of a progestin could decrease its effectiveness as an
      emergency contraceptive. Initiation of hormonal contraception following
      levonorgestrel or the Yuzpe regimen for emergency contraception carries no
      similar concern for decreased method effectiveness.

PMID- 22995539
TI  - Pituitary, ovarian and additional contraceptive effects of an estradiol-based
      combined oral contraceptive: results of a randomized, open-label study.
AB  - BACKGROUND: The estrogen step-down/progestogen step-up 28-day estradiol
      valerate/dienogest (E(2)V/DNG) oral contraceptive effectively inhibits ovulation;
      however, limited data are available regarding its effects on estradiol (E2),
      progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or
      its additional extraovarian contraceptive effects. STUDY DESIGN: In this
      secondary analysis, 100 women received E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2
      mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26 and
      placebo on days 27-28 for one treatment cycle. Measures included the
      presence/absence of cervical mucus; endometrial thickness; and serum E2,
      progesterone, and gonadotropin levels. RESULTS: E2, progesterone, LH and FSH
      levels did not exhibit the typical ovulatory increase and remained relatively
      stable during the cycle. E(2)V/DNG reduced mean maximal endometrial thickness and
      proportion of women with visible cervical mucus. All parameters returned to
      pretreatment levels during the posttreatment cycle. CONCLUSION: E(2)V/DNG
      provides extraovarian contraceptive effects (reducing endometrial thickness and
      cervical mucus production) in addition to inhibiting ovulation, assuring
      contraceptive efficacy.

PMID- 22995541
TI  - Initiation of progestogen-only injectables on different days of the menstrual
      cycle and its effect on contraceptive effectiveness and compliance: a systematic
      review.
AB  - BACKGROUND: Initiation of contraceptive progestogen-only injections
      conventionally require that women delay starting them until menses begin, during
      which time interval a woman may be at risk of unintended pregnancy. Our objective
      was to determine from the literature when a woman can initiate progestogen-only
      injectables for contraception. STUDY DESIGN: We searched MEDLINE and Cochrane
      databases for all articles (in all languages) published in peer-reviewed journals
      between database inception to February 2012, for evidence relevant to starting
      injectables on different days of the menstrual cycle and its impact upon
      contraceptive effectiveness or those that examined different strategies for
      initiation and their effects on compliance and continuation. RESULTS: Eight
      articles met our criteria for inclusion. All studies examined initiation of depot
      medroxyprogesterone (DMPA); no studies of norethisterone enantate were
      identified. Three articles, reported that when DMPA was initiated later than
      Cycle Day 7, ovulation occurred in some women. Approximately 90% of women had
      poor quality cervical mucus within 24 h after they received an injection. Five
      studies of compliance and continuation demonstrated that the use of another
      contraceptive method as a "bridging option" was not successful in helping women
      initiate DMPA. When DMPA was given throughout the menstrual cycle, more women
      were eligible to receive their first injection but only about half returned on
      time for their subsequent injection and some pregnancies occurred. CONCLUSION:
      Ovulation is rare when DMPA is provided within the first 7 days of the menstrual
      cycle. Use of another contraceptive as a "bridging option" until DMPA can be
      initiated has been unsuccessful in helping women initiate DMPA and is associated
      with higher rates of pregnancy.

PMID- 22995540
TI  - Contraception technology: past, present and future.
AB  - Steady progress in contraception research has been achieved over the past 50
      years. Hormonal and nonhormonal modern contraceptives have improved women's lives
      by reducing different health conditions that contributed to considerable
      morbidity. However, the contraceptives available today are not suitable to all
      users, and the need to expand contraceptive choices still exists. Novel products
      such as new implants, contraceptive vaginal rings, transdermal patches and newer
      combinations of oral contraceptives have recently been introduced in family
      planning programs, and hormonal contraception is widely used for spacing and
      limiting births. Concerns over the adverse effects of hormonal contraceptives
      have led to research and development of new combinations with improved metabolic
      profile. Recent developments include use of natural compounds such as estradiol
      and estradiol valerate with the hope to decrease thrombotic risk, in combination
      with newer progestins derived from the progesterone structure or from
      spirolactone, in order to avoid the androgenic effects. Progesterone antagonists
      and progesterone receptor modulators are highly effective in blocking ovulation
      and preventing follicular rupture and are undergoing investigations in the form
      of oral pills and in semi-long-acting delivery systems. Future developments also
      include the combination of a contraceptive with an antiretroviral agent for dual
      contraception and protection against sexually transmitted diseases, to be used
      before intercourse or on demand, as well as for continuous use in dual-protection
      rings. Although clinical trials of male contraception have reflected promising
      results, limited involvement of industry in that area of research has decreased
      the likelihood of having a male method available in the current decade.
      Development of nonhormonal methods is still at an early stage of research, with
      the identification of specific targets within the reproductive system in ovaries
      and testes, as well as interactions between spermatozoa and ova. It is hoped that
      the introduction of new methods with additional health benefits would help women
      and couples with unmet needs to obtain access to a wider range of contraceptives
      with improved acceptability.

PMID- 22995542
TI  - New approaches to male non-hormonal contraception.
AB  - A non-hormonal male contraceptive is a contraceptive that does not involve the
      administration of hormones or hormone blockers. This review will focus on the use
      of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and
      function as approaches to male non-hormonal contraception. Two current lonidamine
      derivatives, adjudin and H2-gamendazole, are in development as male
      contraceptives. These potent anti-spermatogenic compounds impair the integrity of
      the apical ectoplasmic specialization, resulting in premature spermiation and
      infertility. Another approach to male contraceptive development is the inhibition
      of retinoic acid in the testes, as retinoic acid signaling is necessary for
      spermatogenesis. The administration of the retinoic acid receptor antagonist BMS
      189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN
      18,446, which inhibits testicular retinoic acid biosynthesis, effectively
      contracepts rabbits. Hopefully, one of these approaches to non-hormonal male
      contraception will prove to be safe and effective in future clinical trials.

PMID- 22995543
TI  - A comparison of anesthetic regimens using etomidate and propofol in patients
      undergoing first-trimester abortions: double-blind, randomized clinical trial of
      safety and efficacy.
AB  - BACKGROUND: This prospective study compared the safety, recovery time and side
      effects of six distinct general anesthesia regimens for first-trimester surgical
      abortion. STUDY DESIGN: Two hundred forty women scheduled for surgical abortion
      at 6 to 8 weeks of gestation were randomized into three groups (n=40) of
      propofol: group P (2 mg/kg propofol alone), group PF (2 mg/kg propofol+1 mcg/kg
      fentanyl), group PMF (2 mg/kg propofol+1 mcg/kg fentanyl+0.02 mg/kg midazolam)
      and three groups (n=40) of etomidate: group E (0.2 mg/kg etomidate alone), group
      EF (0.2 mg/kg etomidate+1 mcg/kg fentanyl) and group EMF (0.2 mg/kg etomidate+1
      mcg/kg fentanyl+0.02 mg/kg midazolam). Vital signs including pulse oxygen
      saturation (SpO2), mean arterial pressure (MAP) and heart rate were recorded as
      the primary outcomes. The recovery time and side effects were recorded as
      secondary outcomes. RESULTS: During induction, SpO2 and MAP decreased
      significantly in all the three groups of propofol and were significantly lower
      than those in the groups of etomidate. Mean recovery times to both eye opening
      and to obeying commands were significantly shorter in group PF than those in
      groups P and PMF, while there were no significant differences among the three
      groups of etomidate. Compared with the etomidate groups, the incidence of
      injection-induced pain was significantly higher, while the scores of myoclonus
      and postoperative nausea and vomiting were lower, in the three propofol groups.
      Moreover, myoclonus scores as well as nausea and vomiting scores were lower in
      group EMF than in groups E and EF. CONCLUSIONS: The results of this study suggest
      that (a) etomidate is much safer than propofol for first-trimester surgical
      abortions and (b) using a lower dose of etomidate, supplemented with fentanyl and
      midazolam, is more beneficial than the use of etomidate with or without fentanyl
      in reducing adverse effects like myoclonus and postoperative nausea and vomiting.

PMID- 22995544
TI  - Fallopian tube occlusion with a shape memory polymer device: evaluation in a
      rabbit model.
AB  - BACKGROUND: The present study evaluates the feasibility of a shape memory polymer
      (SMP) device for fallopian tube occlusion in rabbits. STUDY DESIGN: The SMP
      contraceptive device is made of poly(dl-lactic acid)-based poly(urethane urea)
      SMP in the shape of a spiral cylinder that was 10 mm long and had a diameter of
      2.6 mm. Using this device, bilateral transuterine fallopian tube occlusions were
      performed in 78 New Zealand white female rabbits. Forty-eight female rabbits
      (group 1) were chosen as the experimental group and were implanted with the SMP
      devices. The remaining 30 female rabbits (group 2) served as the control group,
      which only received an incision in the abdomen but no SMP device. Follow-up
      consisted of hysterosalpingography, histologic evaluation and contraceptive
      effect. In addition, the shape memory behavior and in vivo degradation
      characterization of the SMP device were observed in this study. RESULTS: Under
      heat (37  degrees C) stimulation, the temporary shape SMP device returned to its
      permanent shape within 60 s. The average weight loss percentage of SMP devices
      was 7.0% at 2 weeks and 72.5% at 12 weeks. The inflammatory reactions caused by
      SMP devices were aseptic and nonspecific at 2 and 12 weeks, respectively. The SMP
      device boundaries and the surrounding tissues were obscured by fiber hyperplasia
      in 11/12 tubes at 24 weeks. Hysterosalpingography showed an occluded fallopian
      tube of Group 1 in 6/6 rabbits at 12 weeks and 6/6 rabbits at 24 weeks. No
      pregnancy was found in all 18 rabbits of group 1 (contraceptive rate of 100%);
      all 20 rabbits in the control group were pregnant. CONCLUSION: Biodegradable and
      biocompatible SMP devices could provide reliable, instant and permanent tubal
      occlusion.

PMID- 22995545
TI  - Multi-sensory integration in brainstem and auditory cortex.
AB  - Tinnitus is the perception of sound in the absence of a physical sound stimulus.
      It is thought to arise from aberrant neural activity within central auditory
      pathways that may be influenced by multiple brain centers, including the
      somatosensory system. Auditory-somatosensory (bimodal) integration occurs in the
      dorsal cochlear nucleus (DCN), where electrical activation of somatosensory
      regions alters pyramidal cell spike timing and rates of sound stimuli. Moreover,
      in conditions of tinnitus, bimodal integration in DCN is enhanced, producing
      greater spontaneous and sound-driven neural activity, which are neural correlates
      of tinnitus. In primary auditory cortex (A1), a similar auditory-somatosensory
      integration has been described in the normal system (Lakatos et al., 2007), where
      sub-threshold multisensory modulation may be a direct reflection of subcortical
      multisensory responses (Tyll et al., 2011). The present work utilized
      simultaneous recordings from both DCN and A1 to directly compare bimodal
      integration across these separate brain stations of the intact auditory pathway.
      Four-shank, 32-channel electrodes were placed in DCN and A1 to simultaneously
      record tone-evoked unit activity in the presence and absence of spinal trigeminal
      nucleus (Sp5) electrical activation. Bimodal stimulation led to long-lasting
      facilitation or suppression of single and multi-unit responses to subsequent
      sound in both DCN and A1. Immediate (bimodal response) and long-lasting (bimodal
      plasticity) effects of Sp5-tone stimulation were facilitation or suppression of
      tone-evoked firing rates in DCN and A1 at all Sp5-tone pairing intervals (10, 20,
      and 40 ms), and greater suppression at 20 ms pairing-intervals for single unit
      responses. Understanding the complex relationships between DCN and A1 bimodal
      processing in the normal animal provides the basis for studying its disruption in
      hearing loss and tinnitus models. This article is part of a Special Issue
      entitled: Tinnitus Neuroscience.

PMID- 22995546
TI  - Spectroscopic analyses on interaction of Naphazoline hydrochloride with bovine
      serum albumin.
AB  - The fluorescence and ultraviolet spectroscopy were explored to study the
      interaction between Naphazoline hydrochloride (Naphcon) and bovine serum albumin
      (BSA) at three different temperatures (292, 301, and 310 K) under imitated
      physiological conditions. The quenching mechanism of BSA by Naphacon was
      interpreted using the Stern-Volmer mechanism, and a combined quenching (dynamic
      and static quenching). The binding constants, binding sites and the corresponding
      thermodynamic parameters (DeltaG, DeltaH, and DeltaS) of the interaction system
      were calculated at different temperatures. According to Forster non-radiation
      energy transfer theory, the binding distance between BSA and Naphcon was found to
      be 4.71 nm. Synchronous fluorescence spectroscopy showed the conformation of BSA
      changed in the presence of Naphacon. In addition, the effect of some common metal
      ions (Mg(2+), Ca(2+), Ni(2+), Cu(2+), and Fe(2+)) on the binding constant between
      Naphcon and BSA was examined.

PMID- 22995547
TI  - Optical and infrared absorption spectra of 3d transition metal ions-doped sodium
      borophosphate glasses and effect of gamma irradiation.
AB  - Undoped and transition metals (3d TM) doped sodium borophosphate glasses were
      prepared. UV-visible absorption spectra were measured in the region 200-900nm
      before and after gamma irradiation. Experimental optical data indicate that the
      undoped sodium borophosphate glass reveals before irradiation strong and broad UV
      absorption and no visible bands could be identified. Such UV absorption is
      related to the presence of unavoidable trace iron impurities within the raw
      materials used for preparation of this base borophosphate glass. The TMs-doped
      glasses show absorption bands within the UV and/or visible regions which are
      characteristic to each respective TM ion in addition to the UV absorption
      observed from the host base glass. Infrared absorption spectra of the undoped and
      TMs-doped glasses reveal complex FTIR consisting of extended characteristic
      vibrational bands which are specific for phosphate groups as a main constituent
      but with the sharing of some vibrations due to the borate groups. This criterion
      was investigated and approved using DAT (deconvolution analysis technique). The
      effects of different TMs ions on the FTIR spectra are very limited due to the low
      doping level (0.2%) introduced in the glass composition. Gamma irradiation causes
      minor effect on the FTIR spectra specifically the decrease of intensities of some
      bands. Such behavior is related to the change of bond angles and/or bond lengths
      of some structural building units upon gamma irradiation.

PMID- 22995548
TI  - Fourier domain closed-form formulas for estimation of kinetic parameters in
      reversible multi-compartment models.
AB  - BACKGROUND: Compared with static imaging, dynamic emission computed tomographic
      imaging with compartment modeling can quantify in vivo physiologic processes,
      providing useful information about molecular disease processes. Dynamic imaging
      involves estimation of kinetic rate parameters. For multi-compartment models,
      kinetic parameter estimation can be computationally demanding and problematic
      with local minima. METHODS: This paper offers a new perspective to the
      compartment model fitting problem where Fourier linear system theory is applied
      to derive closed-form formulas for estimating kinetic parameters for the two
      compartment model. The proposed Fourier domain estimation method provides a
      unique solution, and offers very different noise response as compared to
      traditional non-linear chi-squared minimization techniques. RESULTS: The unique
      feature of the proposed Fourier domain method is that only low frequency
      components are used for kinetic parameter estimation, where the DC (i.e., the
      zero frequency) component in the data is treated as the most important
      information, and high frequency components that tend to be corrupted by
      statistical noise are discarded. Computer simulations show that the proposed
      method is robust without having to specify the initial condition. The resultant
      solution can be fine tuned using the traditional iterative method. CONCLUSIONS:
      The proposed Fourier-domain estimation method has closed-form formulas. The
      proposed Fourier-domain curve-fitting method does not require an initial
      condition, it minimizes a quadratic objective function and a closed-form solution
      can be obtained. The noise is easier to control, simply by discarding the high
      frequency components, and emphasizing the DC component.

PMID- 22995549
TI  - Diametric gene-dosage effects as windows into neurogenetic architecture.
AB  - Gene expression can be modulated in two opposite directions, towards higher or
      lower amounts of product. How do diametric changes in gene dosage influence
      neurological development and function? Recent studies of transgenic and knockout
      mouse models, genomic copy-number variants, imprinted-gene expression
      alterations, and sex-chromosome aneuploidies are revealing examples of 'mirror
      extreme' brain and behavior phenotypes, which provide unique insights into
      neurodevelopmental architecture. These convergent studies quantitatively connect
      gene dosages with specific trajectories and outcomes, with important implications
      for the experimental dissection of normal neurological functions, the genetic
      analysis of psychiatric disorders, the development of pharmacological therapies,
      and mechanisms for the evolution of human brain and behavior.

PMID- 22995550
TI  - Gene, brains, and environment-genetic neuroimaging of depression.
AB  - Depression, conceptualized as major depressive disorder (MDD), is a complex
      psychiatric disorder with multiple behavioral changes and alterations in various
      brain regions. Biochemically, serotonin and others substances like GABA,
      glutamate, norepinephrin, adrenaline/noradrenaline play an essential role in the
      pathogenesis of MDD. The paper reviews recent human neuroimaging findings on how
      the genes underlying these biochemical substances modulate neural activity,
      behavior, and ultimately clinical symptoms. Current data provide solid evidence
      that genes related to serotonin impact emotion-related neural activity in the
      amygdala and the anterior cingulate cortex. By contrast, evidence is not as
      strong for genes related to biochemical substances other than serotonin and other
      regions of the brain. The review concludes with discussing future genetic,
      neural, and clinical challenges that point out the central role of gene *
      environment and brain * environment interactions as genetic and neural
      predispositions of depression.

PMID- 22995551
TI  - The molecular basis of social behavior: models, methods and advances.
AB  - Elucidating the molecular and neural basis of complex social behaviors such as
      communal living, division of labor and warfare requires model organisms that
      exhibit these multi-faceted behavioral phenotypes. Social insects, such as ants,
      bees, wasps and termites, are attractive models to address this problem, with
      rich ecological and ethological foundations. However, their atypical systems of
      reproduction have hindered application of classical genetic approaches. In this
      review, we discuss how recent advances in social insect genomics,
      transcriptomics, and functional manipulations have enhanced our ability to
      observe and perturb gene expression, physiology and behavior in these species.
      Such developments begin to provide an integrated view of the molecular and
      cellular underpinnings of complex social behavior.

PMID- 22995552
TI  - Arterial wall histology in chronic pulsatile-flow and continuous-flow device
      circulatory support.
AB  - BACKGROUND: Continuous-flow (CF) ventricular assist devices (VAD) are an
      established option for treatment of end-stage heart failure. However, the effect
      of long-term CF with lack of peripheral arterial wall motions on blood pressure
      regulation and end-organ arterial wall sclerosis, especially in the case of long
      term support (> 3 years), remains unclear. METHODS: Tissue samples obtained at
      autopsy from liver, kidney, coronary arteries, and brain from 27 VAD recipients
      supported for > 180 days between 2000 and 2010 were histologically examined to
      assess vascular alterations, including perivascular infiltrate, intravascular
      infiltrate, wall thickness, thrombosis, endothelial cell swelling, vessel wall
      necrosis, and peri-vascular fibrosis. Pulsatile-flow (PF) devices had been
      inserted in 9 patients and CF devices had been inserted in 16. The pathologist
      was blinded to the group distribution. Demographic, pharmacologic, and clinical
      data were retrospectively analyzed before surgery and during the follow-up period
      of up to 24 months. RESULTS: Median duration of support was 467 days (range, 235
      1,588 days) in the PF group and 263 days (range, 182-942 days) in the CF group.
      Demographic and clinical data before and after surgery were similar. Amiodarone
      was more often used during follow-up in CF group than in the PF group (61% vs
      10%, p = 0.009). Throughout the follow-up period, mean arterial pressure did not
      differ between recipients of the 2 pump types, nor did systolic and diastolic
      pressure, except at 2 weeks after VAD implantation, when systolic blood pressure
      was higher (p = 0.05) and diastolic lower (p = 0.03) in the PF group. Histologic
      studies did not identify any relevant differences in arterial wall
      characteristics between the 2 groups. CONCLUSION: Long-term mechanical
      circulatory support with CF devices does not adversely influence arterial wall
      properties of the end-organ vasculature.

PMID- 22995553
TI  - Serum osteopontin levels as a predictor of portal inflammation in patients with
      nonalcoholic fatty liver disease.
AB  - BACKGROUND: Osteopontin is a secreted phosphorylated glycoprotein that is
      expressed by a variety of cell types and that mediates numerous and diverse
      biological functions. Osteopontin knockout mice are protected from obesity
      induced hepatic steatosis. In the present study, we sought to investigate whether
      serum osteopontin concentrations are associated with liver histology in patients
      with nonalcoholic fatty liver disease. METHODS: Serum levels of osteopontin were
      measured by enzyme-linked immunosorbent assay in 179 well-characterized patients
      with nonalcoholic fatty liver referred for liver histology and 123 control
      subjects. RESULTS: Serum osteopontin levels were markedly higher in patients with
      nonalcoholic fatty liver disease than in controls (p<0.001). Multivariable
      analysis showed that osteopontin levels were strongly and independently
      associated with both portal inflammation (beta=0.294, p<0.01) and serum
      aminotransferase levels (aspartate aminotransferase: beta=0.295, p<0.01; alanine
      aminotransferase; beta=0.285, p<0.01). CONCLUSION: In summary, these data
      demonstrate that serum levels of osteopontin are elevated in nonalcoholic fatty
      liver disease and are a significant independent predictor of portal inflammation
      in this clinical entity.

PMID- 22995554
TI  - Tsukushi controls the hair cycle by regulating TGF-beta1 signaling.
AB  - The hair follicle contains stem/progenitor cells that supply progeny for skin
      development and the hair cycle. Several signaling molecules belonging to the Wnt,
      BMP, shh, and transforming growth factor beta (TGF-beta) signaling cascades are
      involved in the normal hair follicle cycle. However, the systemic mechanism of
      how these humoral factors are controlled remains largely unknown. Previously, we
      reported that Tsukushi (TSK), a member of the small leucine-rich repeat
      proteoglycan family, functions extracellularly as a key coordinator of multiple
      signaling networks. Here, we show that TSK is expressed at the restricted areas
      of hair follicle during the morphogenesis and the hair cycle. Targeted disruption
      of the TSK gene causes the hair cycle to be delayed with low levels of TGF-beta1
      and phosphorylated Smad2/3 (pSmad2/3) expression. Biochemical analysis indicates
      that TSK directly binds to TGF-beta1. Our data suggest that TSK controls the hair
      cycle by regulating TGF-beta1 signaling.

PMID- 22995555
TI  - In vivo knockdown of Brachyury results in skeletal defects and urorectal
      malformations resembling caudal regression syndrome.
AB  - The T-box transcription factor BRACHYURY (T) is a key regulator of mesoderm
      formation during early development. Complete loss of T has been shown to lead to
      embryonic lethality around E10.0. Here we characterize an inducible miRNA-based
      in vivo knockdown mouse model of T, termed KD3-T, which exhibits a hypomorphic
      phenotype. KD3-T embryos display axial skeletal defects caused by apoptosis of
      paraxial mesoderm, which is accompanied by urorectal malformations resembling the
      murine uro-recto-caudal syndrome and human caudal regression syndrome phenotypes.
      We show that there is a reduction of T in the notochord of KD3-T embryos which
      results in impaired notochord differentiation and its subsequent loss, whereas
      levels of T in the tailbud are sufficient for axis extension and patterning.
      Furthermore, the notochord in KD3-T embryos adopts a neural character and loses
      its ability to act as a signaling center. Since KD3-T animals survive until
      birth, they are useful for examining later roles for T in the development of
      urorectal tissues.

PMID- 22995556
TI  - Veterinary-based biopharmaceuticals.

PMID- 22995557
TI  - Temporal artery biopsy: skip it at your patient's peril.

PMID- 22995558
TI  - Evolution of early changes at the vitreoretinal interface after cataract surgery
      determined by optical coherence tomography and ultrasonography.

PMID- 22995560
TI  - Longitudinal study of macular folds by spectral-domain optical coherence
      tomography.

PMID- 22995564
TI  - Characteristics of the peripapillary retinal nerve fiber layer in preterm
      children.

PMID- 22995562
TI  - Accuracy of intraocular lens power calculation formulae in children less than two
      years.

PMID- 22995566
TI  - Endothelial cell density after descemet membrane endothelial keratoplasty: 1 to 5
      year follow-up.

PMID- 22995567
TI  - [Vascular manifestations due to Campylobacter fetus subsp. fetus infection:
      report of two cases].
AB  - INTRODUCTION: Campylobacter fetus is a rare Gram-negative bacteria affecting
      especially elderly and immunocompromised patients, and that is responsible of
      vascular and cutaneous involvement. OBSERVATIONS: We report two cases of C. fetus
      infection in two diabetic male patients, aged 75 and 85 years. The first patient
      was admitted for chronic fever. First-line examinations were inconclusive.
      Combined positron emission tomography and computed imaging tomography (PET-CT)
      diagnosed an infection of a previously operated popliteal aneurysm. The patient
      underwent surgery, and per-operative samples were positive for C. fetus. The
      second patient was admitted for a leg cellulitis. Blood cultures were positive
      for C. fetus. PET-CT found a septic superficial thrombophlebitis. The outcome was
      favorable for both patients with prolonged antibiotic therapy. CONCLUSION:
      Vascular involvement should be suspected in the presence of C. fetus infections.
      PET-CT may be useful, as other imaging modalities are not always contributive.

PMID- 22995568
TI  - Effect of tunical defect size after Peyronie's plaque excision on postoperative
      erectile function: do centimeters matter?
AB  - OBJECTIVE: To demonstrate the effect of the size of the resultant tunical defect
      after plaque excision on postoperative erectile function of patients with
      Peyronie's disease. METHODS: The results of 38 patients with plaque excision and
      dermal grafting were reviewed from April 2007 to June 2011. History, physical
      examination, self-shot photograph, color duplex ultrasonography were done
      preoperatively, and the risk factors for erectile dysfunction were evaluated. The
      tunical defects were >= 3 cm for group 1 and <3 cm for group 2. The postoperative
      need for phosphodiesterase type 5 inhibitors was noted for both groups. The
      International Index of Erectile Function-5 questionnaire was completed by all
      patients. RESULTS: Overall, phosphodiesterase type 5 inhibitors were necessary
      for 13 (34%) of 38 patients; 7 (58.3%) of 12 in group 1 and 6 (23%) of 26 in
      group 2. The risk factors for postoperative erectile dysfunction were
      statistically similar for both groups. If patients with ventral defects were
      excluded from group 2, the number of patients requiring phosphodiesterase type 5
      inhibitors was 4 (17%) of 24. The patients in group 2 answered the fifth question
      (4.6 +/- 0.55) significantly different from those in group 1 (3.7 +/- 0.88).
      CONCLUSION: Plaque excision and dermal grafting can be recommended only for
      highly selected patients with Peyronie's disease with good erectile capacity,
      with a degree of angle not suitable for only plication or Nesbit techniques, for
      patients who do not accept any significant shortening of the penis, and if the
      size of the tunical defect will be <3 cm. Additional techniques on the opposite
      aspect of the lesion are advocated for the remaining curvatures, not to enlarge
      the tunical defect >3 cm.

PMID- 22995569
TI  - Protective effects of bilirubin in an experimental rat model of pyelonephritis.
AB  - OBJECTIVE: To investigate the effects of bilirubin in a rat model of
      pyelonephritis. METHODS: Experimental pyelonephritis was induced in 32 wistar
      rats and 4 groups were formed: group 1 (no treatment), group 2 (antibiotic),
      group 3 (bilirubin), and group 4 (antibiotic + bilirubin). Antibiotic was given
      on days 3 to 8, and bilirubin was administered between days 0 and 8 of bacterial
      inoculation. Half of the rats were killed on the 9th day (early period) and
      histopathological parameters, immunohistochemical renal fibrosis markers,
      apoptosis, and oxidant/antioxidant system activities were evaluated. The rest of
      the rats were killed at the 6th week of the study and evaluated for
      histopathological parameters and renal fibrosis markers. RESULTS: Inflammatory
      activity was significantly lower in rats treated with antibiotic + bilirubin vs
      no treatment group both in the early and late periods. In the late period,
      inflammatory cell intensity was lower in rats treated with bilirubin vs no
      treatment and the antibiotic + bilirubin groups. Interstitial fibrosis/tubular
      atrophy was lower in the antibiotic + bilirubin group vs the no treatment and
      antibiotic groups, and in bilirubin vs antibiotic group. Tissue inhibitor of
      metalloproteinase-1 expression was lower in the bilirubin vs antibiotic group.
      Terminal deoxynucleotidyl transferase mediated 2'-deoxyuridine, 5'-triphosphate
      nick end labeling(+) cells were significantly lower in bilirubin and antibiotic +
      bilirubin groups vs no treatment group. Malondialdehyde levels were significantly
      lower in the antibiotic + bilirubin vs the no treatment group and superoxide
      dismutase activity was significantly higher in the antibiotic and antibiotic +
      bilirubin groups vs the no treatment group. CONCLUSION: Bilirubin may have
      protective effects on pyelonephritis-associated inflammation in both early and
      late periods in addition to fibrosis and apoptosis when applied with antibiotics.
      When used alone, bilirubin may also prevent inflammation (in the late period) and
      apoptosis.

PMID- 22995570
TI  - Contemporary evaluation of the National Comprehensive Cancer Network prostate
      cancer risk classification system.
AB  - OBJECTIVE: To analyze the National Comprehensive Cancer Network prostate cancer
      guidelines pretreatment risk groups in a contemporary series of patients treated
      with radical prostatectomy. METHODS: We analyzed our institutional radical
      prostatectomy database, including all patients with clinically localized disease
      treated from 2000 to 2010. Using the National Comprehensive Cancer Network
      guidelines, the patients were classified into low-, intermediate-, or high-risk
      groups. The pathologic outcomes were assessed, and the biochemical recurrence
      (BCR)-free survival rates were calculated and compared using the log-rank test
      and Cox proportional hazards analysis. RESULTS: A total of 12 821 men met the
      inclusion criteria. The pathologic and 10-year BCR-free survival rates differed
      significantly by risk group (low risk, 92.1%; intermediate risk, 71.0%; and high
      risk, 38.8%; P < .01). Among the intermediate-risk men, the 10-year BCR-free
      survival was significantly greater for men assigned to the intermediate-risk
      group by clinical stage (88.8%) than for those deemed intermediate risk by the
      Gleason score (73.6%) or prostate-specific antigen (PSA) level (79.5%; P = .01).
      Likewise, in the high-risk men, a trend was seen toward improved 5-year BCR-free
      survival for patients with clinical stage T3a tumors (77.8%) compared with those
      considered high risk because of the Gleason score (53.7%) or PSA level (41.0%; P
      = .13). On multivariate analysis, clinical stage, Gleason score, and PSA level
      were all significantly associated with BCR. CONCLUSION: We observed heterogeneous
      outcomes among patients within the National Comprehensive Cancer Network
      intermediate- and high-risk groups. The BCR-free survival rates were superior for
      men with an advanced clinical stage compared with those with an advanced Gleason
      score or elevated PSA level. This within-group heterogeneity must be considered
      when choosing the treatment modality and predicting an individual patient's
      prognosis.

PMID- 22995571
TI  - Preliminary experience with the use of acellular collagen matrix in redo surgery
      for urethrocutaneous fistula.
AB  - OBJECTIVE: To show that splinting of the urethral repair with acellular collagen
      matrix is a safe and useful adjunct in the procedure to manage complex
      urethrocutaneous fistula. Urethrocutaneous fistula is one of the most common
      complications of hypospadias surgery. Management of persistent urethrocutaneous
      fistula is challenging because it is complicated by a lack of or poor quality of
      tissues at the site of repair. METHODS: Between 2006 and 2011, 12 boys underwent
      urethrocutaneous fistula repair (10) or redo urethroplasty (2) using acellular
      collagen matrix by a single surgeon. Mean age was 6.8 years (range 3.1-14.8);
      median follow-up was 2.5 years (range 0.4-3.8). Urethrocutaneous fistula was
      closed and acellular collagen matrix was used as a splint. All the patients were
      assessed by an independent observer; all boys were successfully treated with no
      further recurrence of fistula. RESULTS: On palpation, the previous site of the
      acellular collagen matrix implant was soft and subtle, revealing healthy
      underlying tissues. Cosmetic outcome was excellent in all patients, with no signs
      of scarring or tethering. All patients had a single good urinary stream. Uroflows
      were within normal range of age-matched standardized nomograms with
      nonobstructive bell-shaped curves. One boy had late wound infection, which healed
      with debridement, but had no recurrence of fistula. CONCLUSION: Splinting of the
      urethral repair with acellular collagen matrix in redo surgery is safe and is a
      useful adjunct that effectively prevents further recurrence of complications such
      as urethrocutaneous fistula.

PMID- 22995572
TI  - Identification of T-type calcium channels in the interstitial cells of Cajal in
      rat bladder.
AB  - OBJECTIVE: To investigate the expression and function of T-type calcium channels
      in the interstitial cells of Cajal in rat bladders. METHODS: Bladders were
      harvested from Sprague-Dawley rats. The expression of T-type calcium channels
      subtypes (alpha1G, alpha1H, and alpha1I) in interstitial cells of Cajal were
      identified by double-labeled immunofluorescence analysis and reverse
      transcription-polymerase chain reaction analysis in whole mount preparations of
      rat bladders. The function of T-type calcium channels in freshly isolated
      interstitial cells of Cajal was assessed by detecting the changes of
      intracellular calcium ([Ca(2+)](i)) with preloading fluo-3 AM, and by evaluating
      the changes of the phasic contractions of rat bladder strips after treating with
      mibefradil and glivec. RESULTS: Three T-type calcium channels subtypes, alpha1G,
      alpha1H, and alpha1I, colocalized with c-kit in bladder interstitial cells of
      Cajal by double-labeled immunofluorescence analysis, and this was confirmed using
      reverse transcription-polymerase chain reaction. The T-type calcium channels
      selective blocker, mibefradil (1 MUM), significantly decreased the intracellular
      calcium concentration ([Ca(2+)](i)) in isolated interstitial cells of Cajal (P <
      .01) and inhibited the spontaneous phasic contraction of bladder strips (P <
      .01). Moreover, the c-kit receptor blocker, glivec, significantly decreased the
      [Ca(2+)](i) of interstitial cells of Cajal further (P < .01) and the spontaneous
      phasic contraction of bladder strips. CONCLUSION: T-type calcium channel subtypes
      were confirmed to colocalize in interstitial cells of Cajal in rats bladders,
      which might participate in the spontaneous activity of interstitial cells of
      Cajal and phasic contractions of bladder strips by modulating [Ca(2+)](i) in
      interstitial cells of Cajal.

PMID- 22995573
TI  - Double outlet right ventricle with unilateral absence of left pulmonary artery.
AB  - Congenital absence of unilateral pulmonary artery, either as a primary defect or
      in combination with other congenital cardiovascular malformations, is very rare.
      Double outlet right ventricle pathology in combination with unilateral absence of
      pulmonary artery has only been reported once in the literature. In this report,
      we present our experience with double outlet right ventricle with unilateral
      absence of left pulmonary artery in a 3-year-old female patient who underwent a
      palliative procedure and was scheduled for correction.

PMID- 22995574
TI  - Beyond cortical localization in clinico-anatomical correlation.
AB  - Last year was the 150th anniversary of Paul Broca's landmark case report on
      speech disorder that paved the way for subsequent studies of cortical
      localization of higher cognitive functions. However, many complex functions rely
      on the activity of distributed networks rather than single cortical areas. Hence,
      it is important to understand how brain regions are linked within large-scale
      networks and to map lesions onto connecting white matter tracts. To facilitate
      this network approach we provide a synopsis of classical neurological syndromes
      associated with frontal, parietal, occipital, temporal and limbic lesions. A
      review of tractography studies in a variety of neuropsychiatric disorders is also
      included. The synopsis is accompanied by a new atlas of the human white matter
      connections based on diffusion tensor tractography freely downloadable on
      http://www.natbrainlab.com. Clinicians can use the maps to accurately identify
      the tract affected by lesions visible on conventional CT or MRI. The atlas will
      also assist researchers to interpret their group analysis results. We hope that
      the synopsis and the atlas by allowing a precise localization of white matter
      lesions and associated symptoms will facilitate future work on the functional
      correlates of human neural networks as derived from the study of clinical
      populations. Our goal is to stimulate clinicians to develop a critical approach
      to clinico-anatomical correlative studies and broaden their view of clinical
      anatomy beyond the cortical surface in order to encompass the dysfunction related
      to connecting pathways.

PMID- 22995575
TI  - BLV-CoCoMo-qPCR: a useful tool for evaluating bovine leukemia virus infection
      status.
AB  - BACKGROUND: Bovine leukemia virus (BLV) is associated with enzootic bovine
      leukosis, which is the most common neoplastic disease of cattle. BLV infects
      cattle worldwide, imposing a severe economic impact on the dairy cattle industry.
      Recently, we developed a new quantitative real-time polymerase chain reaction
      (PCR) method using Coordination of Common Motifs (CoCoMo) primers to measure the
      proviral load of known and novel BLV variants in BLV-infected animals. Indeed,
      the assay was highly effective in detecting BLV in cattle from a range of
      international locations. This assay enabled us to demonstrate that proviral load
      correlates not only with BLV infection capacity as assessed by syncytium
      formation, but also with BLV disease progression. In this study, we compared the
      sensitivity of our BLV-CoCoMo-qPCR method for detecting BLV proviruses with the
      sensitivities of two real-time PCR systems, and also determined the differences
      of proviral load with serotests. RESULTS: BLV-CoCoMo-qPCR was found to be highly
      sensitive when compared with the real-time PCR-based TaqMan MGB assay developed
      by Lew et al. and the commercial TaKaRa cycleave PCR system. The BLV copy number
      determined by BLV-CoCoMo-qPCR was only partially correlated with the positive
      rate for anti-BLV antibody as determined by the enzyme-linked immunosorbent
      assay, passive hemagglutination reaction, or agar gel immunodiffusion. This
      result indicates that, although serotests are widely used for the diagnosis of
      BLV infection, it is difficult to detect BLV infection with confidence by using
      serological tests alone. Two cattle were experimentally infected with BLV. The
      kinetics of the provirus did not precisely correlate with the change in anti-BLV
      antibody production. Moreover, both reactions were different in cattle that
      carried different bovine leukocyte antigen (BoLA)-DRB3 genotypes. CONCLUSIONS:
      Our results suggest that the quantitative measurement of proviral load by BLV
      CoCoMo-qPCR is useful tool for evaluating the progression of BLV-induced disease.
      BLV-CoCoMo-qPCR allows us to monitor the spread of BLV infection in different
      viewpoint compared with classical serotest.

PMID- 22995576
TI  - Quantitative and sensitive detection of the SARS-CoV spike protein using
      bispecific monoclonal antibody-based enzyme-linked immunoassay.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein is
      known to mediate receptor interaction and immune recognition and thus it is
      considered as a major target for vaccine design. The spike protein plays an
      important role in virus entry, virus receptor interactions, and virus tropism.
      Sensitive diagnosis of SARS is essential for the control of the disease in
      humans. Recombinant SARS-CoV S1 antigen was produced and purified for the
      development of monoclonal and bi-specific monoclonal antibodies. The hybridomas
      secreting anti-S1 antibodies, F26G18 and P136.8D12, were fused respectively with
      the YP4 hybridoma to generate quadromas. The sandwich ELISA was formed by using
      F26G18 as a coating antibody and biotinylated F26G18 as a detection antibody with
      a detection limit of 0.037MUg/ml (p<0.02). The same detection limit was found
      with P136.8D12 as a coating antibody and biotinylated F26G18 as a detection
      antibody. The sensitivity was improved (detection limit of 0.019MUg/ml), however,
      when using bi-specific monoclonal antibody (F157) as the detection antibody. In
      conclusion, the method described in this study allows sensitive detection of a
      recombinant SARS spike protein by sandwich ELISA with bi-specific monoclonal
      antibody and could be used for the diagnosis of patients suspected with SARS.

PMID- 22995577
TI  - Comparison of the performance of five different immunoassays to detect specific
      antibodies against emerging atypical bovine pestivirus.
AB  - Bovine pestiviruses represent a considerably variable group. In addition to the
      two accepted species BVDV-1 and BVDV-2, a number of atypical bovine pestiviruses
      have been detected both in foetal calf sera and in field samples. The sera
      collected during the initial six weeks of experimental infection of calves with
      atypical pestivirus, BVDV-1 and a combination of both viruses have been examined
      by routine and new diagnostic tests to validate their robustness and sensitivity.
      As expected, virus neutralization tests using homologous virus were able to
      differentiate the two groups infected by BVDV-1 or atypical pestivirus, whereas
      the animals inoculated with a mixture of these two viruses had a reaction pattern
      very similar to the homologous virus alone. It was found that immunoassays using
      whole virus and polyclonal antibodies are the most robust, but all tests examined
      were able to detect antibodies also from cattle infected with atypical pestivirus
      a few weeks after infection. The detection, however, was at a lower level and
      slightly delayed. Statistical validation of the threshold suggested by the
      manufacturer showed that in some cases the reduction of the cut-off values would
      improve the test sensitivity.

PMID- 22995578
TI  - Evaluation of stability and size distribution of sunflower oil-coated micro
      bubbles for localized drug delivery.
AB  - BACKGROUND: Micro bubbles were initially introduced as contrast agents for
      ultrasound examinations as they are able to modify the signal-to-noise ratio in
      imaging, thus improving the assessment of clinical information on human tissue.
      Recent developments have demonstrated the feasibility of using these bubbles as
      drug carriers in localized delivery. In micro fluidics devices for generation of
      micro bubbles, the bubbles are formed at interface of liquid gas through a
      strangulation process. A device that uses these features can produce micro
      bubbles with small size dispersion in a single step. METHODS: A T-junction micro
      fluidic device constructed using 3D prototyping was made for the production of
      mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid
      layer. Stability studies for micro bubbles with diameters different generated
      from a liquid phase of the same viscosity were conducted to evaluate whether
      micro bubbles can be used as drug carriers. The biocompatibility of coating
      layer, the ability to withstand environmental pressure variations combined with
      echogenicity, are key factors that they can safely play the role of drug
      transporters. RESULTS: The normal distribution curve with small dispersion of the
      diameter of bubbles validates the process of generating micro bubbles with low
      value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the
      feasibility of using sunflower oil as the lipid matrix with stable population of
      bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 MUm
      and 121 minutes for micro bubbles with an average diameter of 73.74 MUm,
      considering bubbles with air as gaseous phase. CONCLUSION: The results indicate
      that the micro fluidic device designed can be used for producing micro bubbles
      with low variation coefficient using sunflower oil as a coating of micro bubbles.
      These carriers were stable for periods of time that are long enough for clinical
      applications even when regular air is used as the gas phase. Improved stability
      can be achieved when biocompatible gas with lower permeability is used.

PMID- 22995579
TI  - Gunshot victims at a major level I trauma center: a study of 343,866 emergency
      department visits.
AB  - BACKGROUND: Disturbing trends regarding the sex, age, and race of gunshot victims
      have been reported in previous national studies; however, gunshot trends have not
      been well documented in individual cities in the southeastern United States.
      OBJECTIVES: 1) Analyze trends in gunshot wounds, particularly the association
      between gunshot wounds and race, among victims presenting to a Level I Trauma
      Center in Middle Tennessee; 2) Compare specific characteristics of gunshot
      victims to the general Emergency Department (ED) population. METHODS: This is a
      retrospective cohort study of 343,866 ED visits from 2004 to 2009. RESULTS:
      Compared to the general ED population, gunshot victims were more predominantly
      male (87.5% vs. 43.4%), black (57.6% vs. 29.5%), younger (47.8% under age 25
      years vs. 31.6%), and demonstrated higher Medicaid enrollment (78.6% vs. 44.7%).
      The majority of black gunshot victims were aged 18-25 years (47.1%) and victims
      of assault (65.9%). Non-black gunshot victims suffered more unintentional (40.2%
      vs. 28.2%) and self-inflicted (9.1% vs. 0.4%) injuries and were more evenly
      distributed among ages 18-55 years. Black patients were 3.03 (95% confidence
      interval 2.93-3.14) times more likely to present to this ED for gunshot wounds
      than non-black patients, after controlling for age, sex, and insurance status (p
      < 0.001). CONCLUSIONS: Our study demonstrates that black patients between 18 and
      25 years of age presenting to this trauma center are more likely to be victims of
      gun violence than their non-black counterparts. Our study evaluates trends in gun
      violence in the Southeast, particularly in relation to race, age, and insurance
      status.

PMID- 22995581
TI  - Editorial for "advances in protein-protein interactions".

PMID- 22995580
TI  - Methylphenidate modulates the locus ceruleus neuronal activity in freely behaving
      rat.
AB  - The electrophysiological properties of the locus coeruleus (LC) neurons in
      response to acute and chronic administration of methylphenidate (MPD) were
      investigated. The extracellular LC neuronal activities were recorded from non
      anesthetized, freely behaving rats previously implanted bilaterally with
      permanent semi microelectrodes. The main findings were: (1) On experimental day 1
      (ED1), 87% (94/108) of LC units significantly changed their firing rate after
      initial (acute) MPD (2.5mg/kg, i.p.) administration. The majority of the
      responsive units (80%, 75/94) increased their firing rate; (2) Daily MPD
      (2.5mg/kg) injection was given on ED2 through ED6 followed by 3 washout days (ED7
      to 9). On ED10, all LC units exhibited a significant change of their baseline
      activity compared to their baseline activity on ED1; (3) MPD rechallenge on ED10
      elicits 94% (101/108) of LC units significantly changed their firing rate; the
      majority of them (78%, 79/101) increased their firing rate; (4) The effect of
      rechallenge MPD administration on ED10 were compared to the effect of initial MPD
      on ED1, 98% of the LC units exhibited a significant change in their firing rate.
      41% (43/106) of them exhibited a significant increase in their firing rate while
      59% (63/106) units significantly decreased their firing rate which can be
      interpreted as electrophysiological sensitization or tolerance respectively. In
      conclusion, the majority of LC neurons significantly increased their firing rate
      after acute and chronic MPD administration. This data demonstrated that enhanced
      LC neuronal activities play important role in the effect of MPD.

PMID- 22995582
TI  - Prospective comparison of prognostic values of modified Response Evaluation
      Criteria in Solid Tumours with European Association for the Study of the Liver
      criteria in hepatocellular carcinoma following chemoembolisation.
AB  - BACKGROUNDS: European Association for the Study of the Liver (EASL) and modified
      Response Evaluation Criteria in Solid Tumours (mRECIST) guidelines, which measure
      changes in arterialised hepatocellular carcinoma (HCC), differ in terms of number
      of target lesions (all versus <=2) and calculation method (bidimensional versus
      unidimensional). We compared prognostic values of mRECIST for predicting overall
      survival (OS) with reference to EASL criteria in treatment-naive HCC undergoing
      trans-arterial chemoembolisation (TACE). METHODS: The ability to predict OS
      during longitudinal follow-up was expressed as C-index, and a sample size of 292
      patients was required to validate its equivalence between each criteria.
      Treatment responses were assessed using both guidelines 4weeks after the first
      TACE, using dynamic computed tomography or magnetic resonance imaging. Kaplan
      Meier and Cox regression analyses were used to explore differences in OS between
      responders (complete or partial) and non-responders (stable or progressive
      disease), defined by each method. RESULTS: C-index for EASL and mRECIST
      guidelines was 0.753 and 0.759, respectively, demonstrating equivalence between
      two methods. Differences in median OS between responders and non-responders were
      statistically significant for both EASL (30.1 versus 18.7 months, p<0.001) and
      mRECIST (33.8 versus 17.1 months, p<0.001) guidelines. In addition to
      radiological response, alpha-fetoprotein (p<0.001), tumour number (p<0.001) and
      tumour size (p=0.048) were significant predictors of OS. In multivariate
      analysis, radiological criteria, tumour number and alpha-fetoprotein were
      identified as independent predictors (all p<0.05). CONCLUSION: mRECIST, a simpler
      method, provided prognostic values for predicting OS equivalent to EASL criteria
      in patients with HCC undergoing TACE as an initial treatment modality.

PMID- 22995583
TI  - Gamma-glutamyltransferase, H2O2-induced apoptosis and expression of catalase.

PMID- 22995584
TI  - Induction of apoptosis in human ovarian cancer cells by new anticancer compounds,
      epothilone A and B.
AB  - Epothilones are a new group of compounds with action mechanisms similar to
      taxanes. The aim of this study was to compare the effects of epothilone A (Epo A)
      and epothilone B (Epo B) on ovarian cancer cell line SKOV-3 with those of
      paclitaxel (PTX), a classic taxane. We evaluate glycoprotein P (P-gp) activity in
      the ovarian cancer cell line. Apoptotic and necrotic cell levels were measured by
      double staining with Hoechst 33258 and propidium iodide (PI) as well as Annexin V
      staining. The production of reactive oxygen species (ROS) and changes in
      mitochondrial membrane potential (DeltaPsim) in cells exposed to Epo A, Epo B and
      PTX were studied using specific fluorescence probes, DCFH(2)-DA (2',7'
      dichlorodihydrofluorescein diacetate) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolcarbocyanine). The cytotoxic activity of the drugs was
      determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium
      bromide) test. All probes were analyzed in both the presence and absence of the
      antioxidant N-acetylcysteine (NAC). The results obtained demonstrated that the
      antiproliferative capacity of Epo A and Epo B in SKOV-3 cell line (measured as
      IC(50) after 72 h continuous treatment) was six and five times greater than that
      of PTX's respectively. Epothilones induced timecourse-dependent apoptosis and
      necrosis. Apoptotic and necrotic events were partially blocked by NAC, indicating
      ROS played a substantial role in epothilone-induced apoptosis. Cell death was
      also associated with a decrease in mitochondrial membrane potential, which was
      more pronounced after treatment with epothilones as compared to paclitaxel.

PMID- 22995585
TI  - Human skin penetration of cobalt nanoparticles through intact and damaged skin.
AB  - Cobalt nanoparticles (CoNPs) are produced for several industrial and biomedical
      applications but there is a lack of data on human cutaneous absorption. Cobalt is
      also a skin sensitizer that can cause allergic contact dermatitis. Co applied as
      NPs, due to their small size and high surface, can penetrate into the skin in
      higher amount that bulk material. The aim of this study was to evaluate the
      absorption of Co applied as NPs in both intact and damaged skin. Experiments were
      performed using Franz cells and 1.0 mg cm(-2) of CoNPs was applied as donor phase
      for 24h. Mean Co content of 8.5 +/- 1.2 ng cm(-2) and 1.87 +/- 0.86 MUg cm(-2)
      were found in the receiving solutions of Franz cells when the CoNPs suspension
      was applied on intact skin and on damaged skin, respectively. Twenty-four hours
      Co flux permeation was 76 +/- 49 ng cm(-2)h(-1) in damaged skin with a lag time
      of 2.8 +/- 2.1h. This study suggests that Co applied as NPs is able to penetrate
      the human skin in an in vitro diffusion cell system.

PMID- 22995586
TI  - New role for astroglia in learning: formation of muscle memory.
AB  - Muscle memory can be described as gradual adaptation of muscles over a period of
      time to perform a new movement or action. Its precise mechanism is unknown;
      however, it is now known that when a motor skill is learned it leads to
      significant brain activity. Astrocytes are the most abundant glial cell types in
      the CNS that play an associative active role with neurons in learning and memory.
      They are interconnected to neurons via gap junctions forming astroglial network
      for fast communication and synchronization. We hypothesize that astroglial cells
      play main role in the formation of muscle memory and evaluate it by the
      experimental evidence published so far that indicates role of astroglia on
      various cellular and molecular aspects of muscle memory. The basis of our
      hypothesis is the fact that during training or motor learning period, neuronal
      output data related to learning lead to certain specific pattern for stimulating
      target muscles over a period of time and partly these data are stored in
      astroglial network. This stored data fine tune glial parameters that affect
      synaptic space and neuronal output used to perform rapid motor actions. For the
      validation of our hypothesis, we have generated a computational model for a
      section of neural pathway with astroglial network and have shown that the
      astroglial network by using inhibitory and stimulatory neurotransmitters can
      generate certain patterns, modulate and balance synaptic space across the neural
      pathway during acquisition of muscle memory.

PMID- 22995587
TI  - Public health preparedness for the world's largest mass gathering: 2010 World
      Exposition in Shanghai, China.
AB  - The 2010 World Exposition in Shanghai China (Expo) was the largest mass gathering
      in world history, attracting a record 72 million visitors. More than 190
      countries participated in the Expo, along with more than 50 international
      organizations. The 2010 Expo was six months in duration (May 1 through October
      30, 2010), and the size of the venue site comprised 5.28 square kilometers. Great
      challenges were imposed on the public health system in Shanghai due to the high
      number and density of visitors, long duration of the event, and other risk
      factors such as high temperatures, typhoon, etc. As the major metropolitan public
      health agency in Shanghai, the Shanghai Municipal Center for Disease Control and
      Prevention (SCDC) implemented a series of actions in preparing for, and
      responding to, the potential health impact of the world's largest mass gathering
      to date, which included partnerships for capacity building, enhancement of
      internal organizational structure, risk assessment, strengthened surveillance,
      disaster planning and exercises, laboratory management, vaccination campaign,
      health education, health intervention, risk communication and mass media
      surveillance, and technical support for health inspection. The clear-cut
      organizational structures and job responsibilities, as well as comprehensive
      operational and scientific preparations, were key elements to ensure the success
      of the 2010 World Exposition.

PMID- 22995588
TI  - A prospective, randomized study comparing outcomes and toxicities of intensity
      modulated radiotherapy vs. conventional two-dimensional radiotherapy for the
      treatment of nasopharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: To compare clinical outcomes and toxicities of two
      dimensional conventional radiation therapy (2D-CRT) and intensity modulated
      radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC).
      MATERIALS AND METHODS: Between July 2003 and October 2008, 616 patients with non
      metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT
      (n=310; mean age, 44.8+/-13.6 years) or IMRT (n=306; mean age, 46.7+/-12.5
      years). Clinical outcomes and acute and late toxicities were determined and
      compared. RESULTS: The 2 groups were comparable with respect to all parameters of
      demographics and disease characteristics (all, p>0.05). Median follow-up was 42
      months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in
      the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91%
      for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2%
      in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free
      survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group
      (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D
      CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT
      group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a
      significant difference was only noted for stage III disease. In terms of
      radiation-induced toxicities, patients in IMRT group had significantly lower
      radiation-induced toxicities than those in 2D-CRT group. CONCLUSION: IMRT
      provides improved local-recurrence free survival, especially in late-stage NPC
      patients and is associated with a lower incidence of toxicities.

PMID- 22995589
TI  - Deodorant use and the risk of skin toxicity in patients undergoing radiation
      therapy for breast cancer: a meta-analysis.

PMID- 22995590
TI  - Team care to cure adolescents with braces (avoiding low quality of life, pain and
      bad compliance): a case-control retrospective study. 2011 SOSORT Award winner.
AB  - BACKGROUND: Bracing could be efficacious, given good compliance and quality of
      braces. Recently the SOSORT Brace TREATMENT Management Guidelines (SBTMG) have
      highlighted the perceived importance of the professional teams surrounding braced
      patients. PURPOSE: To verify the impact of a complete rehabilitation team in the
      adolescent patient with bracing. MATERIALS AND METHODS: Design. Initial cross
      sectional study, followed by a retrospective case-control study. POPULATION:
      Thirty-eight patients (15.8 +/- 1.6 years; 26 females; 10 hyperkyphosis, 28
      scoliosis of 29.2 +/- 7.9 degrees  Cobb) extracted from a single orthotist
      database (between January 1, 2008 and September 1, 2009) and treated by the same
      physician; brace wearing at least 15 hours/day for a minimum of 6 months; age 10
      or more. TREATMENT: Braces: Sforzesco, Sibilla, Lapadula or Maguelone. Exercises:
      SEAS. METHODS: Two questionnaires filled in blindly by patients: SRS-22 and one
      especially developed and validated with 25 questions on adherence to treatment.
      Groups (main risk factor): TEAM (private institute: satisfied 44/44 SOSORT
      criteria; grade of teamwork, "excellent") included 13 patients and NOT 25
      (National Health Service Rehabilitation Department: 35/44 SOSORT criteria
      respected; grade, "insufficient"). RESULTS: TEAM was more compliant to bracing
      than NOT (97 +/- 6% vs. 80 +/- 24%) and performed nearly double the exercises (38
      +/- 12 vs. 20 +/- 13 minutes/session). The self-reduction of bracing was
      significant in NOT (from 16.8 +/- 3.7 to 14.8 +/- 4.9 hours/day, , P<0.05); TEAM
      showed a significant reduction in the difficulties due to bracing (from 8.9 +/-
      1.4 to 3.5 +/- 2.0 in 12 months on a 10-point scale, P<0.05). Pain was perceived
      by 55% of NOT versus 7% of TEAM (P < 0.05). The populations did not differ at the
      baseline studied outcomes. The absence of a good team surrounding the patient
      increases by five times the risk of reduced compliance to bracing (odds ratio OR
      5.5 - 95% confidence interval 95CI 3.6-7.4), along with more than 15 times that
      of QoL problems (OR 15.7 - 95CI 13.6-17.9) and pain (OR 16.8 - 95CI 14.5-19.1).
      CONCLUSIONS: Provided the limits of this first study on the topic, the SBTMG
      seems to be important for brace treatment, influencing pain, QoL and compliance
      (and so, presumably, final results). Future studies on the topic are advisable.

PMID- 22995591
TI  - Sensory nerve action potential amplitude is rarely reduced in lumbosacral
      radiculopathy due to herniated disc.
AB  - OBJECTIVE: Normal sensory nerve action potential (SNAP) amplitude is a classical
      neurographic rule whether damage is located proximal to the dorsal root ganglion
      (DRG) as in radiculopathy. The study's aim is to check SNAP reduction in patients
      with lumbosacral radiculopathy due to herniated disc (HD). METHODS: A total of
      108 consecutive patients with lumbosacral monoradiculopathy were prospectively
      enrolled. The diagnosis was based on clinical findings and magnetic resonance
      imaging (MRI). Electromyography of muscles of L4-S1 myotomes, motor neurography
      of peroneal and tibial nerves and sensory neurography of saphenous, superficial
      peroneal and sural nerves were performed. Percentage decrease in SNAP amplitude
      of nerves between healthy and affected sides was calculated. RESULTS: Significant
      SNAP amplitude asymmetry was observed in superficial peroneal nerve in seven
      patients with L5 (12.1%) and in sural nerve in one patient with S1 (2.4%)
      radiculopathies. All these patients had foraminal HD. CONCLUSIONS: SNAP amplitude
      reduction of sensory nerve originating from damaged root is present only in 7% of
      radiculopathies and is likely due to DRG compression when located proximal to the
      spinal foramen or within the intraspinal canal. SIGNIFICANCE: Preservation of
      SNAP amplitude in radiculopathy remains an electrophysiological dogma with a
      little exception. If the reduction of SNAP amplitude affects other nerves, causes
      other than radiculopathy should be sought.

PMID- 22995592
TI  - Influence of parameter settings on paired-pulse-suppression in somatosensory
      evoked potentials: a systematic analysis.
AB  - OBJECTIVE: Paired-pulse somatosensory evoked potentials (SEPs) are a common tool
      to investigate excitability in the human somatosensory cortex. Comparing
      literature about paired-pulse SEP, there is no standard set of stimulation
      parameters, while little is known about the influence of stimulation parameters
      on paired-pulse suppression. METHODS: We analyzed changes of paired-pulse ratios
      by varying repetition rates from 1 to 9Hz, and using stimulus intensities of 250%
      of the sensory threshold and 100%, 120%, and 140% of the motor threshold, which
      are most frequently used in studies using paired-pulse SEPs. RESULTS: We found a
      significant effect of repetition rate on paired-pulse suppression with increasing
      paired-pulse ratios from 1 to 9Hz, which is mainly caused by a change of single
      pulse amplitudes. We found no difference in paired-pulse suppression at the
      tested stimulation intensities. CONCLUSIONS: The extent of paired-pulse ratios
      across different studies should be interpreted with caution due to the high
      dependence on repetition rate, while the results at the commonly used stimulus
      intensities are comparable. SIGNIFICANCE: For an optimized parameter setting with
      sufficient paired-pulse suppression, we suggest a stimulation rate of 1 or 3Hz
      and a stimulation intensity of 250% of sensory threshold or slightly above motor
      threshold.

PMID- 22995593
TI  - Our continuing discussion on Guillain-Barre syndrome criteria.

PMID- 22995594
TI  - Nursing students' perceptions of clinical supervision: the contributions of
      preceptors, head preceptors and clinical lecturers.
AB  - AIM: The aims of the study were 1) to investigate to what extent nursing students
      were satisfied with the supervision provided by facilitators (preceptor, head
      preceptor, and clinical lecturer), 2) to compare nursing students' ratings of
      facilitators' contribution to supervision as supportive and challenging, and 3)
      to examine relationships between facilitators' supportive and challenging
      behavior in supervision and nursing students' perception of fulfillment of
      expected learning outcomes in clinical education. BACKGROUND: Although there are
      many studies on support of students in clinical education, few have addressed
      this from the students' point of view or made comparisons between different
      facilitators. METHODS: A cross-sectional survey study was conducted during April
      to November 2010, where 107 nursing students, from a university in central
      Sweden, answered a questionnaire about supervision immediately after their period
      of clinical education. RESULTS: Supportive behavior in supervision was rated
      higher by students for all facilitator groups as compared with challenging
      behavior. The students rated preceptors and clinical lecturers as more supportive
      than head preceptors and clinical lecturers as providing more challenges than the
      two other facilitator groups. Supportive and challenging behavior in supervision
      explained 39% of the variance in students' overall learning outcomes. However,
      the regression coefficient was only significant for students' ratings of
      supportive behavior for the preceptor. CONCLUSIONS: Nursing students were
      satisfied with facilitators' supervision and by their contribution to fulfillment
      of overall learning outcomes. Comparisons showed that preceptors in a higher
      degree were perceived as supportive while clinical lecturers were perceived as
      more important as challengers for critical thinking, reflection and exchange of
      experiences between students. The model of supervision seems to be promising, but
      the roles across facilitators need to be made clearer, especially the head
      preceptor's role, which seemed to be the most unclear role in this model.

PMID- 22995595
TI  - An integrated educational model for graduate entry nursing cirriculum design.
AB  - The constraints influencing the development of nurse education are widely debated
      and discussed within the academic, professional and public arena. In order to
      challenge these constraints it is proposed that nurse education should promote
      every opportunity for students to engage in critical dialogue with a range of
      influential sources. This paper will report on an integrated educational model
      for graduate entry curriculum design. The model capitalises on the skills and
      attributes students bring to the course, which are collectively termed
      "graduateness," by utilising a range of teaching and learning approaches which
      compliment and build upon each other to foster the characteristics of a capable
      practitioner. It is envisaged that this will better enable those graduating from
      this programme to respond to the changing context of healthcare. 

PMID- 22995596
TI  - Health literacy: use of the Four Habits Model to improve student pharmacists'
      communication.
AB  - OBJECTIVE: To assess whether student pharmacists' communication skills improved
      using the Four Habits Model (FHM) at the St. Louis College of Pharmacy. METHODS:
      During the Fall of 2009 and 2010, student pharmacists in the third professional
      year learned and practiced the FHM. They were given feedback by faculty on three
      of the four Habits, used the FHM for self and peer assessment, and were formally
      evaluated on all four Habits during a standardized patient encounter. RESULTS:
      Student pharmacist performance significantly improved from baseline during both
      Fall 2009 and Fall 2010 in the majority of the Habits assessed. CONCLUSION: Use
      of the FHM in pharmacy education can improve a student pharmacists' ability to
      display the four Habits of communicating and developing relationships with
      patients. Tailoring of the FHM to pharmacy encounters will further enhance the
      utility of this communication framework. PRACTICE IMPLICATIONS: Use of the FHM
      enhances the measurement and assessment of the relational aspects of student
      pharmacist-patient communication skills. Consistent use of the FHM over time is
      likely necessary to fully develop and retain communication skills. The overall
      goal is to improve patient's health literacy and appropriate medication use by
      improving communication and the pharmacist-patient relationship.

PMID- 22995597
TI  - The implementation and evaluation of therapeutic touch in burn patients: an
      instructive experience of conducting a scientific study within a non-academic
      nursing setting.
AB  - OBJECTIVE: Evaluation of therapeutic touch (TT) in the nursing of burn patients;
      post hoc evaluation of the research process in a non-academic nursing setting.
      METHODS: 38 burn patients received either TT or nursing presence. On admission,
      days 2, 5 and 10 of hospitalization, data were collected on anxiety for pain,
      salivary cortisol, and pain medication. Interviews with nurses were held
      concerning research in a non-academic setting. RESULTS: Anxiety for pain was more
      reduced on day 10 in the TT-group. The TT-group was prescribed less morphine on
      day 1 and 2. On day 2 cortisol level before dressing changes was higher in the TT
      group. The situational challenges of this study led to inconsistencies in data
      collection and a high patient attrition rate, weakening its statistical power.
      CONCLUSION: Conducting an effect study within daily nursing practice should not
      be done with a nursing staff inexperienced in research. Analysis of the remaining
      data justifies further research on TT for burn patients with pain, anxiety for
      pain, and cortisol levels as outcomes. PRACTICE IMPLICATIONS: Administering and
      evaluating TT during daily care requires nurses experienced both in TT and
      research, thus leading to less attrition and missing data, increasing the power
      of future studies.

PMID- 22995598
TI  - Understanding pharmacists' experiences with advice-giving in the community
      pharmacy setting: a focus group study.
AB  - OBJECTIVE: To examine the experiences of community pharmacists providing advice
      about symptoms and complementary and alternative medicines (CAM). METHODS: Ten
      licensed pharmacists and 21 student pharmacists working in community settings
      participated in 4 focus groups to discuss: patients' questions about symptoms and
      CAM, comfort level providing advice, and factors prompting physician referrals.
      Focus group recordings were transcribed verbatim and interpreted using thematic
      text analysis. RESULTS: Pharmacists' dual role as advisors and medical liaisons
      emerged as primary themes. Participants reported that patients often seek their
      advice about self-care of symptoms to delay physician visits. Participants were
      comfortable giving advice; lack of medical history decreased their comfort level.
      Most were uncomfortable recommending CAM because of the lack of regulation and
      evidence. Participants suggested that pharmacy curricula expand training on
      symptom triage, pharmacist-patient communication, and CAM to prepare graduates
      for employment in community settings. CONCLUSION: Student and licensed
      pharmacists of this study voiced that they are often asked for advice on symptom
      management, but reported needing training to help provide appropriate advice to
      patients. PRACTICE IMPLICATIONS: The findings suggest that training strategies
      could help pharmacists appropriately triage and advise patients seeking self-care
      advice for their symptoms in the community setting.

PMID- 22995599
TI  - Power estimation using simulations for air pollution time-series studies.
AB  - BACKGROUND: Estimation of power to assess associations of interest can be
      challenging for time-series studies of the acute health effects of air pollution
      because there are two dimensions of sample size (time-series length and daily
      outcome counts), and because these studies often use generalized linear models to
      control for complex patterns of covariation between pollutants and time trends,
      meteorology and possibly other pollutants. In general, statistical software
      packages for power estimation rely on simplifying assumptions that may not
      adequately capture this complexity. Here we examine the impact of various factors
      affecting power using simulations, with comparison of power estimates obtained
      from simulations with those obtained using statistical software. METHODS: Power
      was estimated for various analyses within a time-series study of air pollution
      and emergency department visits using simulations for specified scenarios. Mean
      daily emergency department visit counts, model parameter value estimates and
      daily values for air pollution and meteorological variables from actual data
      (8/1/98 to 7/31/99 in Atlanta) were used to generate simulated daily outcome
      counts with specified temporal associations with air pollutants and randomly
      generated error based on a Poisson distribution. Power was estimated by
      conducting analyses of the association between simulated daily outcome counts and
      air pollution in 2000 data sets for each scenario. Power estimates from
      simulations and statistical software (G*Power and PASS) were compared. RESULTS:
      In the simulation results, increasing time-series length and average daily
      outcome counts both increased power to a similar extent. Our results also
      illustrate the low power that can result from using outcomes with low daily
      counts or short time series, and the reduction in power that can accompany use of
      multipollutant models. Power estimates obtained using standard statistical
      software were very similar to those from the simulations when properly
      implemented; implementation, however, was not straightforward. CONCLUSIONS: These
      analyses demonstrate the similar impact on power of increasing time-series length
      versus increasing daily outcome counts, which has not previously been reported.
      Implementation of power software for these studies is discussed and guidance is
      provided.

PMID- 22995600
TI  - Structural biology of dengue virus enzymes: towards rational design of
      therapeutics.
AB  - Development of anti-dengue therapy represents an urgent un-met medical need.
      Towards antiviral therapy, recent advances in crystal structures of DENV enzymes
      have led to the possibility of structure-based rational design of inhibitors for
      anti-dengue therapy. These include (i) the structure of the 'active' form of the
      DENV protease in complex with a peptide substrate; (ii) the structure of DENV
      methyltransferase bound to an inhibitor that selectively suppresses viral
      methyltransferase, but not human methyltransferases; (iii) the structure of DENV
      RNA-dependent RNA polymerase in complex with a small-molecule compound. This
      review summarizes the structural biology of these three key enzymes (protease,
      methyltransferase, and polymerase) that are essential for DENV replication. The
      new structural information has provided new avenues for development of anti
      dengue therapy.

PMID- 22995601
TI  - Treatment of rats with pioglitazone in the reperfusion phase of focal cerebral
      ischemia: a preclinical stroke trial.
AB  - Thiazolidinediones (TZDs), pioglitazone, rosiglitazone and troglitazone, the
      synthetic agonists for the PPARgamma, administered prior or during ischemic
      insult improve stroke outcome in rodents, post-occlusion treatments yielded
      inconsistent results. In the present experiments carried out according to the
      Stroke Therapy Academic Industry Roundtable (STAIR) guidelines, we studied the
      effects of post-ischemic pioglitazone treatment on the outcome of focal cerebral
      ischemia, inflammatory and apoptotic processes, neuronal degeneration and
      regeneration, blood pressure, heart rate and physiological variables in blood.
      Male Wistar rats were subjected to a 90 min middle cerebral artery occlusion
      (MCAO). Subcutaneous (SC) treatment with vehicle or pioglitazone was initiated 90
      min after MCAO, i.e. in the post-ischemic, reperfusion phase and continued on 2
      (2 day-experiment, protocol 1) or 5 (5-day experiment, protocol 2) consecutive
      days. In the 2-day experiment, pioglitazone at a dose of 2.5 mg/kg body weight
      (bw) reduced infarct volume by 31% and oedema by 43% on day 2 after MCAO and
      attenuated the infiltration of ischemic cortical tissue with activated microglia
      and macrophages. The slight reduction in infarct volume by approximately 18%,
      detected in rats treated with 10 mg/kg bw pioglitazone did not reach statistical
      significance. The neurological scores of sham-operated rats treated with vehicle
      or 10 mg/kg bw pioglitazone were not significantly different. In rats subjected
      to cerebral ischemia, post-ischemic treatment with either dose of pioglitazone
      alleviated particular motor deficits and sensory impairments on day 2 after MCAO.
      A single injection of 10 mg/kg bw pioglitazone in the reperfusion phase (90 min
      after the onset of reperfusion) did not modify systolic and diastolic blood
      pressure, heart rate and physiological variables compared to vehicle-treated rats
      at any time point after MCAO. In the 5-day experiment, continuous post-occlusion
      treatment with 2.5 mg/kg body weight pioglitazone significantly reduced cerebral
      infarction by 29% and improved the partial paralysis of the forelimb and
      alleviated sensory deficits. In the peri-infarct cortex, pioglitazone effectively
      suppressed the accumulation of activated microglia/macrophages, inhibited
      neuronal degeneration and promoted neuroregeneration and formation of neuronal
      networks. The current results provide evidence that pioglitazone treatment in the
      post-ischemic, reperfusion phase improves the recovery from ischemic stroke.
      Neuroprotective effects of pioglitazone are mediated by inhibition of post
      ischemic inflammation and neuronal degeneration, protection of neurones against
      ischemic injury and by promoting of neuronal regeneration. Our data together with
      previous findings favour the view that pioglitazone is a promising candidate for
      clinical stroke trials.

PMID- 22995602
TI  - Increased excitability of spinal pain reflexes and altered frequency-dependent
      modulation in the dopamine D3-receptor knockout mouse.
AB  - Frequency-dependent modulation and dopamine (DA) receptors strongly modulate
      neural circuits in the spinal cord. Of the five known DA receptor subtypes, the
      D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly
      inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3
      receptor knockout mouse (D3KO), we investigated the physiological consequences of
      D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord,
      the initial integration site for the processing of pain signaling. In the D3KO
      spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch
      reflex are converted from depression to facilitation, but its effects on longer
      latency and pain-associated reflex responses and the effects of FM have not been
      studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit
      reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test)
      over wild type (WT) controls. Electrophysiological and pharmacological approaches
      in the isolated spinal cord in vitro showed that constant current stimulation of
      dorsal roots at a pain-associated frequency was associated with a significant
      reduction in the frequency-dependent modulation of longer-latency reflex (LLRs)
      responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of
      the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand,
      pregabalin, but not DA, was able to restore the frequency-dependent modulation of
      the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated
      LLRs and proprioceptive MSRs are differentially modulated by frequency,
      dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role
      for the DA D3 receptor in pain modulation and identify the D3KO as a possible
      model for increased nociception.

PMID- 22995603
TI  - Are diabetic patients at increased risk of arrhythmias?

PMID- 22995604
TI  - Feasibility of peripheral venous access for temporary right ventricular pacing.
AB  - INTRODUCTION: In this brief report, we present our experience from placing
      temporary pacing electrodes through peripheral venous access sites, at bedside,
      in a series of patients needing temporary pacing. METHODS: Consecutive patients
      requiring temporary pacing were selected. The median cubital or the basilic vein
      of the left upper extremity were used for catheterization at the bedside in all
      cases. RESULTS: 25 patients (17 men, age 64.6 +/- 11.8) were included. The
      procedure was successful in 21 cases (84%), 18 of which were completed without
      the need for fluoroscopic guidance. The pacing leads remained for 4.2 +/- 2.2
      days. As expected, no serious complications related to venous puncture were
      observed. Although patients were allowed to be mobilized within the ward and
      engage in limited movements of the catheterized arm, in only one case was the
      lead displaced, requiring repositioning. CONCLUSIONS: We provide observational
      evidence that the use of peripheral venous access for temporary pacing lead
      insertion (with no fluoroscopic guidance, as default strategy) is a safe and
      feasible choice that might be considered as an alternative to central vein
      catheterization.

PMID- 22995605
TI  - Percutaneous mitral valve repair using the edge-to-edge technique: first Greek
      experience.
AB  - INTRODUCTION: Mitral valve (MV) repair is the treatment of choice for
      degenerative mitral regurgitation (MR), but the surgical options for functional
      MR are limited. Percutaneous edge-to-edge MV repair using the MitraClip system
      has evolved as a new tool for the treatment of certain anatomical subsets of both
      functional and degenerative MR. We present the first Greek series of MV repair
      using the MitraClip. METHODS: Five symptomatic patients (age 75 +/- 9 years,
      logistic EuroSCORE 29 +/- 11%) with moderate-tosevere (n=2) or severe (n=3) MR
      underwent MV repair using the MitraClip. All patients were treated with one clip
      and there were no primary adverse events. RESULTS: Acute MR reduction by 3 grades
      was achieved in 2 patients and by 2 grades in 3 patients (reduction 2 grades in
      100%). The total procedure time was 2.9 +/- 2 hours (median 2 hours), the length
      of the ICU stay was 1 +/- 0 day and the total length of hospital stay was 3.2 +/-
      0.6 days. All patients reported functional status improvement by 1 month (mean
      NYHA class improved from 3.0 +/- 0.3 to 1.6 +/- 0.6). CONCLUSION: Our initial
      experience with percutaneous MV repair using the MitraClip system demonstrated
      that it can be performed safely, resulting in substantial acute echocardiographic
      and early clinical improvement.

PMID- 22995606
TI  - Common single nucleotide polymorphisms of the p22phox NADPH oxidase subunit do
      not influence aortic stiffness in young, healthy adults.
AB  - INTRODUCTION: Aortic stiffness is a valuable biomarker for stratifying
      cardiovascular risk. NADPH oxidase regulates oxidative status in vessels; its
      single nucleotide polymorphisms (SNPs) modify the redox state of carriers and may
      lead to noxious structural alterations and affect the vasomotor properties of
      arteries. We hypothesized that genetic variability of NADPH oxidase would be
      accompanied by differences in aortic stiffness; to this end, we explored the
      interplay of pulse wave velocity (PWV), a measure of aortic stiffness, with
      common SNPs of the CYBA gene that encodes the p22phox subunit of NADPH oxidase.
      METHODS: 289 young, healthy adults were studied. The -930A/G, A640G and C242T
      CYBA SNPs were genotyped and PWV was measured. Differences in PWV across
      genotypes were examined in unadjusted models and after adjustment for
      confounders. RESULTS: Genetic variability of the examined SNPs did not result in
      changes of aortic stiffness. In unadjusted models, PWV did not differ across
      genotypes for the -930A/G (p=0.20), A640G (p=0.65) or C242T SNP (p=0.50). In
      stepwise multiple linear regression analysis only sex, age and systolic blood
      pressure emerged as independent predictors of PWV. CONCLUSIONS: Common genetic
      variants of NADPH oxidase do not influence aortic stiffness in young, healthy
      adults.

PMID- 22995607
TI  - J-curve phenomenon: a matter of debate.

PMID- 22995608
TI  - The cytoskeleton of the cardiac muscle cell.

PMID- 22995609
TI  - Mild therapeutic hypothermia in out-of-hospital cardiac arrest survivors.

PMID- 22995610
TI  - Unroofed coronary sinus as a cause of right heart dilatation in an elderly
      patient.

PMID- 22995611
TI  - Mitral valve regurgitation: use of the standard and the latest echocardiographic
      techniques for establishing the diagnosis.
AB  - An 80-year-old man had severe mitral regurgitation caused by myxomatous
      degeneration of the leaflets and perforation of the anterior leaflet. The patient
      underwent a transthoracic and transoesophageal echocardiographic study, and three
      dimensional echo was used to reinforce the diagnosis. Modern echocardiographic
      techniques appear to open new horizons in the study and management of valvular
      diseases, although they are still a long way from replacing traditional methods.

PMID- 22995612
TI  - Correlation of arm position and exercise test interpretation.
AB  - ST-segment changes during exercise testing can be attributed mainly to ischemia,
      but also, in some patients, to other physiological parameters, such as body
      position or hyperventilation, making ECG exercise test interpretation more
      complex. Here we describe the case of a patient who had an
      electrocardiographically positive exercise test, in order to illustrate the
      correlation between arm position and ST changes during exercise testing.

PMID- 22995613
TI  - Acute myocardial infarction in a patient with coronary artery aneurysm and
      Crohn's disease.
AB  - Crohn's disease is a chronic inflammatory disorder of unknown cause involving the
      gastrointestinal tract. Complications from the cardiovascular system seem to be
      uncommon in patients with Crohn's disease. We present a case of a 37-year-old man
      with a known history of Crohn's disease, who was admitted to our hospital with
      acute myocardial infarction. An aneurysm of a totally occluded circumflex
      coronary artery was revealed during the attempt at primary intervention. The
      artery was successfully opened and the aneurysm was sealed with the use of 2
      covered stents.

PMID- 22995614
TI  - Interventional cardiology for structural heart disease.

PMID- 22995615
TI  - Ionising radiation: not the big bad wolf, but definitely not little red riding
      hood.

PMID- 22995616
TI  - A first aid training course for primary health care providers in Nagorno
      Karabagh: assessing knowledge retention.
AB  - INTRODUCTION: Conflict in the South Caucasus' Nagorno Karabagh region has damaged
      health facilities and disrupted the delivery of services and supplies as well as
      led to depletion of human and fixed capital and weakened the de facto
      government's ability to provide training for health care providers. PROBLEM: In
      response to documented medical training deficits, the American University of
      Armenia organized a first aid training course (FATC) for primary health care
      providers within the scope of the USAID-funded Humanitarian Assistance Project in
      Nagorno Karabagh. This paper reports the follow-up assessments conducted to
      inform policy makers regarding FATC knowledge and skill retention and the
      potential need for periodic refresher training. METHODS: Follow-up assessments
      were conducted six months and 18 months following the FATC to assess the
      retention of knowledge, attitudes, and self-reported practices. Eighty-four
      providers participated in the first follow-up and 210 in the second. The
      assessment tool contained items addressing the use and quality of the first aid
      skills, trainee's evaluation of the course, and randomly selected test questions
      to assess knowledge retention. RESULTS: At both follow-up points, the
      participants' assessment of the course was positive. More than 85% of the
      trainees self-assessed their skills as "excellent" or "good" and noted that
      skills were frequently practiced. Scores of approximately 58% on knowledge tests
      at both the first and second follow-ups indicated no knowledge decay between the
      first and second survey waves, but substantial decline from the immediate post
      test assessment in the classroom. CONCLUSION: The trainees assessed the FATC as
      effective, and the skills covered as important and well utilized. Knowledge
      retention was modest, but stable. Refresher courses are necessary to reverse the
      decay of technical knowledge and to ensure proper application in the field.

PMID- 22995617
TI  - Substrate-like water soluble lipase inhibitors from Filipendula kamtschatica.
AB  - Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu
      people in Japan, but its chemical constituents are not much studied. Pancreatic
      lipase inhibitors are a promising tool for the treatment of obesity. We searched
      for natural lipase inhibitors from F. kamtschatica and two new compounds were
      isolated along with the known flavonoid glycoside. The structure elucidation of
      new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-L-threonic acid
      and 3-O-caffeoyl-4-O-galloyl-L-threonic acid, which can be recognized as a
      pancreatic lipase's substrate-like structure. The isolated compounds all showed
      an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3
      O-caffeoyl-4-O-galloyl-L-threonic acid, possessed the most potent activity with
      IC(50) value showing an order lower value compared to others. The substrate-like
      structure of the new compounds seemed to be important for their activity.

PMID- 22995618
TI  - A rhodamine-deoxylactam based sensor for chromo-fluorogenic detection of nerve
      agent simulant.
AB  - N-(rhodamine B)-deoxylactam-5-amino-1-pentanol (dRB-APOH) was designed and
      prepared as the chromo-fluorogenic sensor for detection of a nerve agent simulant
      via analyte triggered tandem phosphorylation and opening of the intramolecular
      deoxylactam. The successful detection of diethyl chlorophosphate suggests the
      utility of rhodamine-deoxylactams as the chromo-fluorogenic signal reporting
      platform for design of sensors targeting reactive chemical species via various
      chemistries.

PMID- 22995619
TI  - Trypsin resistance of a decapeptide KISS1R agonist containing an Nomega
      methylarginine substitution.
AB  - Metastin/kisspeptin is an amidated peptide with 54 amino acid residues isolated
      from human placental tissues as a ligand of the orphan G-protein-coupled receptor
      KISS1R that is expressed throughout the central nervous system and in a variety
      of endocrine and gonadal tissues. Compared to the full-length metastin protein,
      the N-terminal truncated peptide metastin(45-54) has 3-10 times higher receptor
      affinity and enhanced ability to increase intracellular calcium concentration
      which is essential for activation of protein kinases involved in intracellular
      signaling in a number of pathways that affect reproduction and cell migration.
      However, metastin(45-54) is rapidly inactivated in serum. In this study, we
      designed and synthesized a number of metastin(45-54) analogs and evaluated their
      agonistic activity and trypsin resistance. Among analogs with substitutions of
      arginine at position 53, N(omega)(-)methylarginine analog 8 showed 3-fold more
      potent agonistic activity compared with metastin(45-54). Furthermore, analog 8
      was shown to resist trypsin cleavage between positions 53 and 54. This
      substitution may be useful in the development of other Arg-containing peptides
      for which the avoidance of cleavage is desired.

PMID- 22995620
TI  - Identification of a potent and metabolically stable series of fluorinated
      diphenylpyridylethanamine-based cholesteryl ester transfer protein inhibitors.
AB  - A novel series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester
      transfer protein is described. Optimization of the urea moiety, particularly by
      incorporation of fluorine, is explored to balance in vitro metabolic stability
      with CETP potency in the whole plasma assay.

PMID- 22995621
TI  - Substituted thiazoles VII. Synthesis and antitumor activity of certain 2
      (substituted amino)-4-phenyl-1,3-thiazole analogs.
AB  - A novel series of 2-acetamido- or 2-propanamido-4-(4-substituted phenyl)-1,3
      thiazoles (11-34) was designed and synthesized. Compounds were subjected to
      National Cancer Institute (NCI) in vitro assessment for their antitumor activity,
      at a single dose of 10 MUM. Most of the investigated compounds exhibited broad
      spectrum antitumor activity. Compounds 19 and 28 believed to be the most active
      members in this study, with MG-MID GI(50), TGI, and LC(50) values of 2.8, 11.4,
      44.7; and 3.3, 13.1, 46.8, respectively. Compounds 19 and 28 proved to be nine
      and sevenfold more active than the standard antitumor drug 5-FU, respectively.

PMID- 22995622
TI  - Studies on the antimicrobial properties of N-acylated ciprofloxacins.
AB  - Fluoroquinolone antibiotics have been a mainstay in the treatment of bacterial
      diseases. The most notable representative, ciprofloxacin, possesses potent
      antimicrobial activity; however, a rise in resistance to this agent necessitates
      development of novel derivatives to prolong the clinical lifespan of these
      antibiotics. Herein we have synthesized and analyzed the antimicrobial properties
      of a library of N-acylated ciprofloxacin analogues. We find that these compounds
      are broadly effective against Gram-positive and Gram-negative bacteria, with many
      proving more effective than the parental drug, and several possessing MICs <=1.0
      MUg/ml against methicillin-resistant Staphylococcus aureus and Bartonella
      species. An analysis of spontaneous mutation frequencies reveals very low
      potential for resistance in MRSA compared to existing fluoroquinolones. Mode of
      action profiling reveals that modification of the piperazinyl nitrogen by
      acylation does not alter the effect of these molecules towards their bacterial
      target. We also present evidence that these N-acylated compounds are highly
      effective at killing intracellular bacteria, suggesting the suitability of these
      antibiotics for therapeutic treatment.

PMID- 22995623
TI  - Antioxidant properties of Mannich bases.
AB  - The biological importance of antioxidants influenced to synthesize some curcumin
      related compounds as potential antioxidants. Accordingly, a series of 2,4-diaryl
      3-azabicyco[3.3.1]nonan-9-ones were synthesized with polyphenolic and/or
      polymethoxyphenyl groups by modified Mannich condensations. The yield was
      significantly improved using BF(3).SiO(2) as heterogeneous catalyst under mild
      conditions. Stereochemistry of all the synthesized compounds was established as
      twin-chair with an equatorial disposition of the aryl groups, through their NMR
      and XRD interpretations. The ABNs 8 (curcumin analog) and 10 (bis
      demethoxycurcumin analog) showed an effective profile over curcumin, alpha
      tocopherol, and vitamin C by chemical methods. Further, the efficiency of one of
      the active molecules, ABN 10, was demonstrated by its intracellular ROS
      inhibition activity on RAW 264.7 macrophage cells by FACS analysis in dose
      dependent manner.

PMID- 22995624
TI  - Discovery of novel dihydroimidazothiazole derivatives as p53-MDM2 protein-protein
      interaction inhibitors: synthesis, biological evaluation and structure-activity
      relationships.
AB  - Starting with Nutlins as an initial lead, we designed and generated bicyclic
      scaffolds aiming to place cis-bischlorophenyl moiety at the equivalent location
      where the hydrophobic interaction with MDM2 could be expected. As a result, we
      discovered novel MDM2 inhibitors possessing a dihydroimidazothiazole scaffold.
      Further exploration of the side chains on the dihydroimidazothiazole scaffold
      aided by molecular modeling resulted in compounds exhibiting almost comparable in
      vitro potency to Nutlin-3a.

PMID- 22995625
TI  - Synthesis and biological evaluation of a novel 99mTc cyclopentadienyl tricarbonyl
      complex ([(Cp-R)99mTc(CO)3]) for sigma-2 receptor tumor imaging.
AB  - We report the design, synthesis and biological evaluation of a novel (99m)Tc 4-(4
      cyclohexylpiperazine-1-yl)-butan-1-one-1-cyclopentadienyltricarbonyl technetium
      ([(99m)Tc]5) as a potential SPECT tracer for imaging of sigma(2) receptors in
      tumors. [(99m)Tc]5 was prepared in 25+/-5% isolated radiochemical yield with
      radiochemical purity of >99% via double-ligand transfer (DLT) reaction from the
      ferrocene precursor 2b (4-(4-cyclohexylpiperazine-1-yl)-1-ferrocenylbutan-1-one).
      The corresponding Re-complex 4 and the ferrocenyl complex 2b showed relatively
      high affinity towards sigma(2) receptors in in vitro competition binding assay
      (K(i) values of 4 and 2b were 64.4+/-18.5 nM and 43.6+/-21.3 nM, respectively)
      and moderate to high selectivity versus sigma(1) receptors
      (K(i)sigma(1)/K(i)sigma(2) ratios were 12.5 and 95.5, respectively). The logD
      value of [(99m)Tc]5 was determined to be 2.52+/-0.33. Biodistribution studies in
      mice revealed comparably high initial brain uptake of [(99m)Tc]5 and slow
      washout. Administration of haloperidol 5 min prior to injection of [(99m)Tc]5
      significantly reduced the radiotracer uptake in brain, heart, lung, and spleen by
      40-50% at 2h p.i.. Moreover, [(99m)Tc]5 showed high uptake in C6 glioma cell
      lines (8.6%) after incubation for 1h. Blocking with haloperidol to compete with
      [(99m)Tc]5 significantly reduced the cell uptake. Preliminary blocking study in
      C6-brain-tumor bearing rats showed that [(99m)Tc]5 binds to sigma receptors in
      the brain-tumor specifically. These results are encouraging for further
      exploration of (99m)Tc-labeled probes for sigma(2) receptor tumor imaging in
      vivo.

PMID- 22995626
TI  - Terminal branching pattern of the right coronary artery in left-dominant hearts:
      a cadaveric study.
AB  - BACKGROUND: Left coronary dominance has been reported to be associated with
      increased mortality and severity in case of myocardial ischemia involving left
      coronary artery. The present cadaveric study was proposed to objectively study
      and document the termination and branching pattern of the right coronary artery
      in left-coronary-dominant hearts in relation to the blood supply to the posterior
      surface of the right ventricle. METHODS: Seventy-five cadaveric hearts were
      studied. The coronary vessels were injected with colored cellulose acetate
      butyrate and dissected. The coronary dominance was determined. In left-dominant
      hearts, branches and termination of the right coronary artery were studied.
      RESULTS: Left coronary dominance was found in 13% of the specimens. The number of
      ventricular branches was found to be present as 0, 1, 2, and 4 in two, four, two,
      and two of the cases, respectively. The average length of the ventricular branch
      was 12.7 mm with a range of 5-35 mm. The atrial branch was found in 50% of
      hearts, varying from 2 to 3 mm in length. In three hearts, the acute marginal
      artery did not give any posterior ventricular branch, while two, three, and five
      posterior ventricular branches were seen in four, two, and one heart(s),
      respectively. The length of the posterior ventricular arteries was between 5 and
      15 mm. CONCLUSION: The RCA is an inconstant and unreliable source of posterior
      right ventricular perfusion in a significant percentage of population with left
      coronary-dominant hearts. This might be the reason for the increased morbidity
      and mortality seen in the event of left coronary ischemia.

PMID- 22995627
TI  - Globus pallidus deep brain stimulation for refractory idiopathic restless legs
      syndrome.
AB  - OBJECTIVE: The neuroanatomic substrate of restless legs syndrome (RLS) is
      unknown. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) and
      other targets is used to treat Parkinson's disease (PD), and RLS symptoms
      associated with PD have been reported to improve when GPi DBS is used in that
      population. We wish to test whether GPi DBS can improve idiopathic RLS. METHOD:
      We implanted bilateral GPi DBS in a subject with refractory idiopathic RLS.
      RESULTS: The GPi cells recordings were dissimilar to those of PD. Clinically, the
      patient had a good, but far from complete, response, which more prominently
      affected the urge to move and involuntary movements than the painful component.
      CONCLUSION: DBS for RLS remains investigational.

PMID- 22995628
TI  - Natural lysogenization and transduction in Salmonella enterica serovar
      Choleraesuis by bacteriophage P1.
AB  - It has been reported that bacteriophage P1 injects DNA into serovar Choleraesuis
      without evidence of productive infection. However, we found that P1 generates
      progeny and is capable of transduction in serovar Choleraesuis. This is not the
      case with other serovars of Salmonella enterica we tested. Therefore, P1 could
      play a role in serovar Choleraesuis evolution and contribute to its genetic
      manipulation and analysis.

PMID- 22995629
TI  - Dimensions of the inventory of depressive symptomatology as predictors of the
      course of depressive and anxiety disorders.
AB  - For depressive and anxiety disorders general course characteristics are known.
      However, prognosis varies among patients with the same diagnosis. The current
      study investigated whether the more homogeneous symptom dimensions of
      mood/cognition and anxiety/arousal, could be used to predict more differentiated
      prognoses than with overall course-categories. One-thousand-and-fifty-three
      subjects with a depressive and/or anxiety disorder from the Netherlands Study of
      Depression and Anxiety (NESDA) were assessed at baseline and at 2-year follow-up.
      Dimensions of mood/cognition and anxiety/arousal were extracted from the Self
      Report Inventory of Depressive Symptomatology (IDS-SR). Diagnoses at baseline and
      follow-up were assessed with a standardized psychiatric interview. Course
      trajectories were assessed with a life chart interview. Increased mood/cognition
      scores predicted single depression (OR = 1.80) and comorbid depression-anxiety
      (OR = 2.00 [CI: 1.28-2.54]) at follow-up and unfavourable course trajectories of
      depressive symptomatology (OR = 1.94-2.08). Increased anxiety/arousal predicted
      single panic disorder at follow-up (OR = 2.21 [CI: 1.62-3.03]) and unfavourable
      course trajectories of anxiety symptomatology (OR = 1.38-1.42). All associations
      remained significant when adjusted for other prognostic factors, including
      baseline diagnosis. In conclusion, the widely used IDS-SR can be used to measure
      two dimensions that contribute prognostic value on top of other, previously known
      prognostic factors.

PMID- 22995630
TI  - Anxiety, distress and anger among British nationals in Japan following the
      Fukushima nuclear accident.
AB  - BACKGROUND: The 2011 earthquake and tsunami in Japan caused a meltdown at the
      Fukushima nuclear power plant. AIMS: To quantify emotional responses among
      British nationals in Japan and to assess whether perceptions about the incident
      or accessing information about it were associated with responses. METHOD: A total
      of 284 participants randomly selected from official records completed a survey
      that included instruments to measure emotional responses. RESULTS: In total, 16%
      met the criteria for distress, 29.7% reported high anxiety relating to the
      incident and 30.4% reported high anger. Perceptions that strongly predicted these
      outcomes included feeling uncertain, being unable to rule out harmful exposure,
      and believing that exposure would have severe or hidden health effects or be
      difficult to detect. Using information sources was associated with higher
      emotional outcome, particularly for sources perceived to have low credibility.
      CONCLUSIONS: Reducing uncertainty and improving the credibility of information is
      essential in reducing the psychological impact of radiological disasters.

PMID- 22995631
TI  - Betel-quid dependence and oral potentially malignant disorders in six Asian
      countries.
AB  - BACKGROUND: Despite gradual understanding of the multidimensional health
      consequences of betel-quid chewing, information on the effects of dependent use
      is scant. AIMS: To investigate the 12-month prevalence patterns of betel-quid
      dependence in six Asian populations and the impact of this dependence on oral
      potentially malignant disorders (OPMD). METHOD: A multistage random sample of
      8922 participants was recruited from Taiwan, mainland China, Indonesia, Malaysia,
      Sri Lanka and Nepal. Participants were evaluated for betel-quid dependency using
      DSM-IV and ICD-10 criteria and assessed clinically for oral mucosal lesions.
      RESULTS: The 12-month prevalence of dependence was 2.8-39.2% across the six Asian
      samples, and 20.9-99.6% of those who chewed betel-quid were betel-quid dependent.
      Men dominated the prevalence among the east Asian samples and women dominated the
      prevalence in south-east Asian samples. 'Time spent chewing' and 'craving' were
      the central dependence domains endorsed by the Chinese and southern/south-east
      Asian samples respectively, whereas the Nepalese samples endorsed 'tolerance' and
      'withdrawal'. Dependency was linked to age, gender, schooling years, drinking,
      smoking, tobacco-added betel-quid use and environmental accessibility of betel
      quid. Compared with non-users, those with betel-quid dependency had higher pre
      neoplastic risks (adjusted odds ratios 8.0-51.3) than people with non-dependent
      betel-quid use (adjusted odds ratio 4.5-5.9) in the six Asian populations.
      CONCLUSIONS: By elucidating differences in domain-level symptoms of betel-quid
      dependency and individual and environmental factors, this study draws attention
      to the population-level psychiatric problems of betel-quid chewing that undermine
      health consequences for OPMD in six Asian communities.

PMID- 22995632
TI  - Out-patient psychological therapies for adults with anorexia nervosa: randomised
      controlled trial.
AB  - BACKGROUND: Very limited evidence is available on how to treat adults with
      anorexia nervosa and treatment outcomes are poor. Novel treatment approaches are
      urgently needed. AIMS: To evaluate the efficacy and acceptability of a novel
      psychological therapy for anorexia nervosa (Maudsley Model of Anorexia Nervosa
      Treatment for Adults, MANTRA) compared with specialist supportive clinical
      management (SSCM) in a randomised controlled trial. METHOD: Seventy-two adult out
      patients with anorexia nervosa or eating disorder not otherwise specified were
      recruited from a specialist eating disorder service in the UK. Participants were
      randomly allocated to 20 once weekly sessions of MANTRA or SSCM and optional
      additional sessions depending on severity and clinical need (trial registration:
      ISRCTN62920529). The primary outcomes were body mass index, weight and global
      score on the Eating Disorders Examination at end of treatment (6 months) and
      follow-up (12 months). Secondary outcomes included: depression, anxiety and
      clinical impairment; neuropsychological outcomes; recovery rates; and additional
      service utilisation. RESULTS: At baseline, patients randomised to MANTRA were
      significantly less likely to be in a partner relationship than those receiving
      SSCM (3/34 v. 10/36; P<0.05). Patients in both treatments improved significantly
      in terms of eating disorder and other outcomes, with no differences between
      groups. Strictly defined recovery rates were low. However, MANTRA patients were
      significantly more likely to require additional in-patient or day-care treatment
      than those receiving SSCM (7/34 v. 0/37; P = 0.004). CONCLUSIONS: Adults with
      anorexia nervosa are a difficult to treat group. The imbalance between groups in
      partner relationships may explain differences in service utilisation favouring
      SSCM. This study confirms SSCM as a useful treatment for out-patients with
      anorexia nervosa. The novel treatment, MANTRA, designed for this patient group
      may need adaptations to fully exploit its potential.

PMID- 22995633
TI  - One stage resection of spontaneous rupture of hepatocellular carcinoma in the
      triangular ligament with diaphragm invasion: case report and review of the
      literature.
AB  - A spontaneous rupture of hepatocellular carcinoma (HCC) can lead to extensive
      hemorrhage and is a rare but life-threatening event. A 58-year-old male patient
      with no history of trauma presented at our institution with severe epigastric
      pain and abdominal distension for 6 h. His blood pressure was a 60/40 mmHg, and
      pulse rate was 132/min. Abdominal contrast enhanced computed tomography (CT)
      imaging revealed a ruptured mass under the left diaphragm and fluid collection in
      the upper abdomen, flanks and pelvic cavity. Exploratory laparotomy confirmed the
      presence of an active bleeding tumor in the triangular ligament invading into the
      diaphragm. The tumor was resected with an appropriate diaphragm margin. The
      resected tumor was 5 cm in diameter and pathologically identified as
      hepatocellular carcinoma with a negative surgical margin. This case report shows
      that ruptured hepatocellular carcinoma should be considered in the differential
      diagnosis of non-traumatic hemoperitoneum. And it is necessary to set a surgical
      plan for unpredictable HCC rupture with direct diaphragm invasion.

PMID- 22995634
TI  - Impact of the epithelial dysplasia grading and Ki67 proliferation index in the
      adjacent non-malignant mucosa on recurrence and survival in head and neck
      squamous cell carcinoma.
AB  - This study aimed to evaluate the association between several different aspects of
      disease in head and neck squamous cell carcinoma (HNSCC): morphological grading,
      Ki67 proliferation index (PI), invasive front, adjacent non-malignant mucosa
      (ANMM), recurrence and overall survival of the patients. Sixty-four fully
      reviewed and followed-up patients with primary HNSCC were matched according to
      recurrence of the lesion and placed in one of two groups of 32 cases. Chi-square
      and Fisher's exact tests were used to analyze the clinicopathological parameters
      between both groups of patients. Association between Ki67 PI and
      clinicopathological parameters was also analyzed through chi-square and Fisher's
      exact tests with the binary logistic regression model used as a multivariate
      analysis. In addition, survival analysis was also performed. Our results showed
      that high-risk dysplasia in ANMM and high Ki67 PI in ANMM of HNSCC exhibited a
      higher risk of tumor recurrence. Survival analysis showed that T3/T4 tumor sizes
      and high Ki67 PI were significantly associated with an increase in the risk of
      death in multivariate analysis. Our results revealed that high-risk dysplasia and
      high Ki67 PI of the ANMM are parameters which are indicative of tumor recurrence.
      Furthermore, T3/T4 tumor sizes and high Ki67 PI in the invasive front appear to
      be important prognostic tools for HNSCC.

PMID- 22995635
TI  - Prognostic significance of glomerular and tubulointerstitial morphometry in
      idiopathic membranous nephropathy.
AB  - The purpose of our study was to investigate the prognostic value of clinical and
      pathological, in particular glomerular and tubulointerstitial morphometric
      variables in idiopathic membranous nephropathy (IMN). We prospectively followed
      60 Caucasian patients diagnosed with idiopathic membranous nephropathy for at
      least 2 years or until primary outcome (>=50% permanent decrease in estimated
      glomerular filtration rate or death). Glomerular and tubulointerstitial
      morphometric variables at the time of renal biopsy were analyzed with respect to
      this outcome. Univariate analysis revealed that significant negative prognostic
      factors for this outcome were higher cholesterol and smaller albumin
      concentrations, higher creatinine and maximal 24-h proteinuria, higher grade of
      nephroangiosclerosis, higher glomerular basement membrane thickness and
      glomerulopathy index, higher interstitial fibrosis and tubular atrophy percentage
      and higher injury score. In multivariate analysis, only the maximal 24-h
      proteinuria and interstitial fibrosis and tubular atrophy percentage were
      independent predictors of this outcome. The results suggest that morphometric
      analysis, mainly quantitative measurement of interstitial fibrosis and tubular
      atrophy percentage, injury score, glomerular basement membrane thickness and
      glomerulopathy index could be used as an additional method for risk
      stratification of patients with idiopathic membranous nephropathy.

PMID- 22995636
TI  - Fluorogenic tagging of protein 3-nitrotyrosine with 4-(aminomethyl)benzene
      sulfonate in tissues: a useful alternative to Immunohistochemistry for
      fluorescence microscopy imaging of protein nitration.
AB  - Protein tyrosine nitration is a common biomarker of biological aging and diverse
      pathologies associated with the excessive formation of reactive oxygen and
      nitrogen species. Recently, we suggested a novel fluorogenic derivatization
      procedure for the detection of 3-nitrotyrosine (3-NT) using benzylamine
      derivatives to convert specifically protein- or peptide-bound 3-NT to a highly
      fluorescent benzoxazole product. In this study, we applied this procedure to
      fluorogenic derivatization of protein 3-NT in sections from adult rat cerebellum
      to: (i) test this method for imaging nitrated proteins in fixed brain tissue
      sections and (ii) compare the chemical approach to immunohistochemical labeling
      with anti-3-NT antibodies. Immunofluorescence analysis of cerebellar sections
      using anti-3-NT antibodies showed differential levels of immunostaining in the
      molecular, Purkinje, and granule cell layers of the cerebellar cortex; in
      agreement with previous reports, the Purkinje cells were most highly labeled.
      Importantly, fluorogenic derivatization reactions of cerebellar proteins with 4
      (aminomethyl)benzene sulfonic acid (ABS) and K(3)Fe(CN)(6) at pH 9, after sodium
      dithionite reduction of 3-NT to 3-aminotyrosine, showed a very similar pattern of
      relative intensity of cell labeling and improved resolution compared with
      antibody labeling. Our data demonstrate that ABS derivatization may be either a
      useful alternative to or a complementary approach to immunolabeling in imaging
      protein nitration in cells and tissues, including under conditions of dual
      labeling with antibodies to cell proteins, thus allowing for cellular
      colocalization of nitrated proteins and any protein of interest.

PMID- 22995637
TI  - Oxidative damage and genotoxicity biomarkers in transfused and untransfused
      thalassemic subjects.
AB  - Chronic anemia and tissue hypoxia increase intestinal iron absorption and
      mitochondrial impairment in thalassemic patients. Regular blood transfusions
      improve hemoglobin levels but determine an iron overload that induces reactive
      oxygen species (ROS) overproduction. The aim of this study was to assess cellular
      oxidative damage by detection of ROS, lipid peroxidation, 8-oxo-dG, and
      mitochondrial transmembrane potential (Deltapsi(m)) in transfused and
      untransfused thalassemic patients. We have also evaluated genotoxicity by CBMN
      and comet assay. Our data show that ROS and lipid hydroperoxides are
      significantly higher in thalassemic patients than in controls, especially in
      untransfused thalassemia intermedia patients. Moreover, the latter have a
      significant decrease in Deltapsi(m) that highlights the energetic failure in
      hypoxic state and the ROS overproduction in the respiratory chain. 8-OHdG levels
      are higher in thalassemics than in controls, but do not differ significantly
      between the two patient groups. Both genotoxicity biomarkers highlight the
      mutagenic potential of hydroxyl radicals released by iron in the Fenton reaction.
      Values for percentage of DNA in the comet tail and micronuclei frequency,
      significantly higher in transfused patients, could also be due to active
      hepatitis C virus infection and to the many drug treatments. Our biomonitoring
      study confirms the oxidative damage in patients with thalassemia major and shows
      an unexpected cellular oxidative damage in untransfused thalassemic patients. In
      addition to iron overload, the results highlight the important role played by
      hypoxia-driven mitochondrial ROS overproduction in determining oxidative damage
      in beta-thalassemias.

PMID- 22995638
TI  - Elution of TEGDMA and HEMA from polymerized resin-based bonding systems.
AB  - OBJECTIVES: In this study the amount of TEGDMA and HEMA eluted from several
      adhesive systems was quantified. METHODS: The adhesive systems were applied
      according to manufacturers' instructions in an analytic vial. The adhesive
      systems used were (abbreviation and producer in parenthesis): cmf adhesive
      system((r)) (CMF) (Saremco), ENAbond (EB) (Micerium), Optibond FL (OB) (Kerr),
      Adper Scotchbond Multi-Purpose (SB) (3M ESPE), Silorane System Adhesive (SSA) (3M
      ESPE), Syntac Classic (SC) (Ivoclar Vivadent) and XP Bond (XPB) (Dentsply). After
      preparation the specimens were immersed in methanol or distilled water for a
      period from 1d to 30d at 37 degrees C. Eluted TEGDMA and HEMA were determined by
      gas chromatographic-mass spectrometry (GC-MS). RESULTS: Following TEGDMA elution
      from adhesives was found (MUg/ml; mean and standard deviation(sd); 1d/30d;
      methanol): SC 0.93(0.8)/0.68(0.5), SSA 0.27(0.09)/0.16(0.04) and XPB
      0.25(0.1)/0.19(0.09). TEGDMA eluted from EB, CMF, OB, and SB was always below
      detection limit. TEGDMA water elution from each adhesive was about 1/5 lower,
      compared to the corresponding TEGDMA methanol elution. Following HEMA elution was
      found (MUg/ml; mean(sd); 1d/30d; methanol): SB 3.42(0.9)/2.02(1.2), EB
      3.07(2.2)/2.15(2.2), XPB 2.47(1.6)/1.89(1.1), OB 1.4(0.7)/0.82(0.2) and SSA
      0.44(0.2)/0.17(0.07). HEMA eluted from CMF and SC was always below detection
      limit. HEMA water elution from each adhesive was about 1/10 lower, compared to
      the corresponding HEMA methanol elution. SIGNIFICANCE: SC, SSA, and XPB eluted
      TEGDMA. SB, EB, XPB, OB, and SSA eluted HEMA. CMF eluted neither HEMA nor TEGDMA.

PMID- 22995640
TI  - [A rare case of acute cardiac failure following percutaneous aortic valve
      replacement: the secondary migration of the prosthetic valve].

PMID- 22995639
TI  - Novel dental restorative materials having low polymerization shrinkage stress via
      stress relaxation by addition-fragmentation chain transfer.
AB  - OBJECTIVES: To produce a reduced stress dental restorative material while
      simultaneously maintaining excellent mechanical properties, we have incorporated
      an allyl sulfide functional group into norbornene-methacrylate comonomer resins.
      We hypothesize that the addition-fragmentation chain transfer (AFCT) enabled by
      the presence of the allyl sulfide relieves stress in these methacrylate-based
      systems while retaining excellent mechanical properties owing to the high glass
      transition temperature of norbornene-containing resins. METHODS: An allyl sulfide
      containing dinorbornene was stoichiometrically formulated with a ring-containing
      allyl sulfide-possessing methacrylate. To evaluate the stress relaxation effect
      as a function of the allyl sulfide concentration, a propyl sulfide-based
      dinorbornene, not capable of addition-fragmentation, was also formulated with the
      methacrylate monomer. Shrinkage stress, the glass transition temperature and the
      elastic modulus were all measured. The composite flexural strength and modulus
      were also measured. ANOVA (CI 95%) was conducted to determine differences between
      the means. RESULTS: Increasing the allyl sulfide content in the resin
      dramatically reduces the final stress in the norbornene-methacrylate systems.
      Both norbornene-methacrylate resins demonstrated almost zero stress (more than
      96% stress reduction) compared with the conventional BisGMA/TEGDMA 70/30wt%
      control. Mechanical properties of the allyl sulfide-based dental composites were
      improved to the point of being statistically indistinguishable from the control
      BisGMA-TEGDMA by changing the molar ratio between the methacrylate and norbornene
      functionalities. SIGNIFICANCE: The allyl sulfide-containing norbornene
      methacrylate networks possessed super-ambient T(g), and demonstrated
      significantly lower shrinkage stress when compared with the control
      (BisGMA/TEGDMA 70-30wt%). Although additional development remains, these low
      stress materials exhibit excellent mechanical properties which are appropriate
      for use as dental restorative materials.

PMID- 22995641
TI  - [Inhaled agents in neuroanaesthesia for intracranial surgery: pro or con].
AB  - Isoflurane, desflurane and sevoflurane all preserve cerebrovascular carbone
      dioxide (CO(2)) reactivity. They are all concentration-dependant cerebral
      vasodilatators and decrease cerebral metabolism. Sevoflurane induces the smallest
      cerebral vasodilatation and preserve cerebral autoregulation up to 1.5CAM,
      compared to isoflurane and desflurane which impair it upon 1CAM. Propofol has
      been compared to inhaled agents. Propofol preserve cerebrovascular CO(2)
      reactivity, blood flow-metabolism coupling, cerebral autoregulation and has no
      vasodilatation effect. None of the three inhaled agents induce any clinical
      relevant increase of intracranial pressure (ICP), but studies were conducted in
      patients without any intracranial hypertension (ICHT). However, compared to
      propofol, ICP and brain swelling were higher with inhaled agents, more with
      isoflurane compared to sevoflurane. Finally, neuroprotective properties have been
      described in experimental model for all the inhaled agents but clinical proofs
      are still lacking. In conclusion, for intracranial surgery without any ICHT
      inhaled agents can be used as a maintenance anesthetic with a preference for
      sevoflurane. In case of ICHT or a risk of ICHT during the surgery, propofol is
      preferred for it slightest effect on ICP and cerebral hemodynamic.

PMID- 22995642
TI  - Survey data with sampling weights: is there a "best" approach?

PMID- 22995643
TI  - Temperature, traffic-related air pollution, and heart rate variability in a panel
      of healthy adults.
AB  - BACKGROUND: Both ambient temperature and air pollution have been associated with
      alterations in cardiac autonomic function, but the responsive patterns associated
      with temperature exposure and the interactive effects of temperature and air
      pollution remain largely unclear. OBJECTIVES: We investigated the associations
      between personal temperature exposure and cardiac autonomic function as reflected
      by heart rate variability (HRV) in a panel of 14 healthy taxi drivers in the
      context of traffic-related air pollution. METHODS: We collected real-time data on
      study subjects' in-car exposures to temperature and traffic-related air
      pollutants including particulate matter with an aerodynamic diameter <=2.5 MUm
      (PM(2.5)) and carbon monoxide (CO) and HRV indices during work time (8:30-21:00)
      on 48 sampling days in the warm season (May-September) and cold season (October
      March). We applied mixed-effects models and loess models adjusting for potential
      confounders to examine the associations between temperature and HRV indices.
      RESULTS: We found nonlinear relationships between temperature and HRV indices in
      both the warm and cold seasons. Linear regression stratified by temperature
      levels showed that increasing temperature levels were associated with declines in
      standard deviation of normal-to-normal intervals over different temperature
      strata and increases in low-frequency power and low-frequency:high-frequency
      ratio in higher temperature range (>25  degrees C). PM(2.5) and CO modified these
      associations to various extents. CONCLUSIONS: Temperature was associated with
      alterations in cardiac autonomic function in healthy adults in the context of
      traffic-related air pollution.

PMID- 22995644
TI  - The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of
      oncogenic function of BCR-ABL in human chronic myeloid leukemia.
AB  - BACKGROUND: Resistance to tyrosine kinase inhibitors (TKIs) remains a challenge
      in management of patients with chronic myeloid leukemia (CML). A better
      understanding of the BCR-ABL signalling network may lead to better therapy.
      FINDINGS: Here we report the discovery of a novel downstream target of BCR-ABL
      signalling, PRL-3 (PTP4A3), an oncogenic tyrosine phosphatase. Analysis of CML
      cancer cell lines and CML patient samples reveals the upregulation of PRL-3.
      Inhibition of BCR-ABL signalling either by Imatinib or by RNAi silencing BCR-ABL
      reduces PRL-3 and increases cleavage of PARP. In contrast, the amount of PRL-3
      protein remains constant or even increased in response to Imatinib treatment in
      drug resistant cells expressing P210 T315I. Finally, analysis with specific shRNA
      shows PRL-3 involvement in the proliferation and self-renewal of CML cells.
      CONCLUSIONS: These data support a role for PRL-3 in BCR-ABL signalling and CML
      biology and may be a potential therapeutic target downstream of BCR-ABL in TKI
      resistant mutant cells.

PMID- 22995645
TI  - The differential effects of OX1R and OX2R selective antagonists on morphine
      conditioned place preference in naive versus morphine-dependent mice.
AB  - Conditioned place preference (CPP) has been associated with orexinergic
      (hypocrtinergic) system activation in naive mice; however, the distinct role of
      different receptors of orexin in this paradigm has not been characterized yet.
      Moreover, the relationship between orexins and morphine in dependent mice may not
      be equal to naive mice and seems noteworthy to investigate. We investigated the
      effects of systemic administration of orexin-1-receptor antagonist, SB 334867,
      and orexin-2 receptor antagonist, TCS-OX2-29 on the acquisition and expression of
      morphine conditioned place preference (CPP) in both naive and morphine-dependent
      mice. We tested SB 334867 in three doses (10, 20 and 30 mg/kg), TCS-OX2-29 in two
      doses (5 and 10 mg/kg) and morphine with highest effective dose based on our dose
      response experiment (5 mg/kg). Our results revealed that while SB 334867
      suppressed CPP acquisition and expression in naive mice, it failed to block CPP
      acquisition and expression in morphine dependent animals. In contrast, TCS-OX2-29
      suppressed CPP acquisition and expression in both naive and dependent mice
      significantly. The rewarding effect of morphine has stronger correlation with
      orexin-2 receptors in morphine-dependent mice while it depends on both kinds of
      receptors in naive mice. This finding, if confirmed in other studies, persuades
      us to further investigate the role of orexin-2 receptor antagonists as potent
      drugs in addiction treatment.

PMID- 22995646
TI  - Effect of allicin on promastigotes and intracellular amastigotes of Leishmania
      donovani and L. infantum.
AB  - Anti-leishmanial activity of allicin (=diallyl thiosulphinate) has been tested in
      vitro against promastigotes and intracellular amastigotes of Leishmania donovani
      and Leishmania infantum. Macrophage infections have been carried out in vitro in
      the murine cell line J774 and ex vivo with peritoneal macrophages from BALB/c
      mice with a modified method to isolate metacyclic promastigotes. The compound has
      shown a significant in vitro effect on the multiplication of promastigotes of L.
      donovani and L. infantum in a time- and dose-dependent manner. It has been shown
      for the first time the inhibition of multiplication of intracellular amastigotes
      of Leishmania by allicin. Inhibitory concentrations of the compound were in the
      micromolar range (10-30 MUM) for both Leishmania species. Antileishmanial effect
      of allicin apparently was not related to products of degradation of the molecule
      as assessed by mass spectrometry analysis. Inhibitory activity of allicin against
      promastigotes and intracellular amastigotes increased when the compound was added
      to the cultures every 24 h. Two administrations of 5 MUM allicin inhibited by ca.
      50% the proliferation of Leishmania amastigotes. Low toxicity for mammalian cells
      of this compound suggests the interest of exploring the value of allicin in
      combined therapy against leishmanial infections.

PMID- 22995647
TI  - Impaired awareness of deficits in Alzheimer's disease: the role of everyday
      executive dysfunction.
AB  - The present study analyzed the awareness of deficits in 117 mild Alzheimer's
      disease participants. Since few studies have examined the cognitive and
      behavioral domains of reduced awareness in detail, we performed a domain-specific
      assessment using the Awareness of deficit Questionnaire - Dementia scale with the
      novel aim of describing the relationship with everyday executive dysfunction.
      Through the use of the subtests of the Behavioral Assessment of the Dysexecutive
      Syndrome, we hypothesized that executive cognitive functions may play an
      important role in the reduced awareness of deficits. We also considered other
      variables of interest to provide a novel comprehensive explanation of this
      phenomenon. Our first approach to the study was a factor analysis considering the
      role of these variables in the awareness of deficits; subsequently, regression
      analysis models were used to define which variables were associated with a
      reduction of awareness in cognitive and behavioral domains. In particular, the
      factors retained from the factor analysis, in terms of inhibition, self
      monitoring, set-shifting, and mood orientation changes, appear to be important
      skills for awareness of instrumental activities of daily living (R(2) = .32). We
      also found hypo manic mood orientation and a tendency through apathy to be
      prominent indications of reduced behavioral awareness (R(2) = .13).

PMID- 22995648
TI  - Expression of tissue levels of matrix metalloproteinases and their inhibitors in
      breast cancer.
AB  - BACKGROUND: We examined mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1,
      and TIMP-2 in human breast cancer tissues, and the association between their
      expression and clinicopathological variables. PATIENTS AND METHODS: Breast tissue
      samples from 120 patients with breast cancer were available for this study. To
      determine mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2,
      semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was
      carried out on tumor and normal tissues, respectively. RESULTS: Mean MMP-2, MMP
      7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the breast cancer was
      significantly higher than in the normal tissue. In terms of tumor size and lymph
      node metastasis of breast cancer, the differences in MMP-2, MMP-7, MMP-9, and MT1
      MMP mRNA expression levels were significant. CONCLUSION: The association between
      the increased expression of MMP-2, MMP-7, MMP-9, and MTI-MMP and
      clinicopathological parameters reflects a role in predicting the aggressive
      behavior of breast cancer.

PMID- 22995649
TI  - Abiraterone acetate for metastatic prostate cancer.

PMID- 22995650
TI  - Aprepitant for management of severe pruritus related to biological cancer
      treatments: a pilot study.
AB  - BACKGROUND: Itch is a common side-effect of treatment with anti-EGFR antibodies
      and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess
      the effects of aprepitant-a neurokinin receptor inhibitor-for management of
      severe pruritus induced by biological drugs. METHODS: In this single-group,
      prospective study, we consecutively enrolled 45 outpatients with metastatic solid
      tumours treated with biological drugs at the Campus Bio-Medico Hospital of Rome,
      Rome, Italy, between September, 2010, and November, 2011. We classified patients
      into two groups: a refactory group, for patients with pruritis refractory to
      standard treatment, or a naive group, for patients who had not been previously
      treated for pruritis. Aprepitant (125 mg on day 1; 80 mg on day 3; 80 mg on day
      5) was given to patients in the refractory group after at least 1 week of
      standard systemic treatment. In the naive group, aprepitant was given in the same
      schedule as the refractory group, after first onset of severe pruritus. Intensity
      of itch was evaluated by Visual Analogue Scale (VAS) score. The primary endpoint
      was change in median VAS score. This trial is registered with ClinicalTrials.gov,
      number NCT01683552. FINDINGS: Median VAS in the refractory group was 8.00 (95% CI
      7.93-8.57) at baseline and 1.00 (0.00-2.00) after 1 week of treatment with
      aprepitant (p<0.0001). In the naive group, VAS score was 8.00 (7.43-8.37) at
      baseline and 0.00 (0.06-1.08) after 1 week of treatment (p<0.0001). 41 (91%)
      patients responded to aprepitant (ie, had a >50% reduction in intensity of
      pruritis) and pruritus recurred in only six (13%) patients. No adverse events
      related to aprepitant occurred. INTERPRETATION: Aprepitant decreases severe
      pruritus induced by biological treatments; it is an old drug, widely available,
      and therefore easy to add to the armamentarium of supportive treatment. Although
      to our knowledge no other studies of the anti-itch activity of aprepitant are
      planned, the results of our trial warrant confirmation in phase 2 and 3 trials.
      FUNDING: None.

PMID- 22995651
TI  - 9/11 survivors to get free cancer treatment.

PMID- 22995652
TI  - Aprepitant for pruritus: drug-drug interactions matter.

PMID- 22995654
TI  - Long-term renal outcomes of episodic urinary tract infection in diabetic
      patients.
AB  - OBJECTIVE: Urinary tract infection (UTI) exists in 9%-20% of female and 3%-11% of
      male patients with diabetes. Diabetic patients experience increased risk of
      bacteremia, hospitalization, and mortality; however, few studies report long-term
      renal outcomes of episodic UTI in diabetic patients with chronic kidney disease
      (CKD). RESEARCH DESIGN AND METHODS: We investigated 225 diabetic patients
      admitted with UTI from 2001 to 2011. Based on the glomerular filtration rate
      (GFR) on admission, we divided the patients into early- (GFR >=30 ml/min; n=131)
      and late-stage (stages 4 and 5, GFR <30 ml/min; n=94) CKD groups. We compared
      admission risk factors, post-UTI GFR decline and its long term trend between
      these groups. RESULTS: Poor glycemic control contributed to admission with UTI in
      the early- and late-stage CKD patients (glycosylated hemoglobin: (9.7+/-2.8%
      versus 8.6+/-2.6%). Early-stage CKD patients exhibited higher urinary glucose.
      Besides, acute kidney injury (AKI) occurred on admission in late-stage CKD
      patients (mean eGFR 14.2 ml/min). However, if the infection was cured, almost all
      diabetic patients reverted to their GFR trends 6 months later. CONCLUSIONS: Late
      stage CKD diabetic patients with UTI are at increased risk of superimposed AKI.
      Almost all patients gradually reverted to their GFR trend later after infection
      was cured. Early recognition of complicating AKI factors and aggressive treatment
      of symptomatic UTI instead of antibiotic prophylaxis for asymptomatic bacteriuria
      are suggested.

PMID- 22995656
TI  - Saccular aortic aneurysm that resembled a mediastinal neoplasm.
AB  - INTRODUCTION: Saccular aortic arch aneurysms in unusual sites may be misdiagnosed
      as a neoplasm. We present the case of a rare saccular aortic arch aneurysm
      between trachea and esophagus that resembled a mediastinal neoplasm in the
      preoperative findings. PRESENTATION OF CASE: A 63-year-old male with an abnormal
      mediastinal shadow on chest X-ray was referred to the hospital. An axial plain
      computed tomogram of the chest revealed mediastinal soft tissue next to the right
      side of the aortic arch resembling a neoplasm originating from the gap between
      the trachea and the esophagus. The coronal view constructed by enhanced 64-row
      multi detector computed tomography revealed the soft tissue was an aneurysm
      arising from the inner side of the aortic arch. An aortic arch replacement was
      performed via a median sternotomy. DISCUSSION: A thoracic aortic aneurysm
      sometimes behaves like a mediastinal neoplasm. The multiple cross-sectional image
      from multidetector computed tomography was useful for the correct diagnosis of
      such an aneurysm. CONCLUSION: The possibility of an aneurysm should be considered
      whenever a mass in contact with the aortic wall is identified.

PMID- 22995657
TI  - Editorial for the MedIA special issue on MICCAI 2011.

PMID- 22995655
TI  - Is the mitochondrial outermembrane protein VDAC1 therapeutic target for
      Alzheimer's disease?
AB  - Mitochondrial dysfunction and synaptic damage have been described as early events
      in Alzheimer's disease (AD) pathogenesis. Recent research using AD postmortem
      brains, and AD mouse and cell models revealed that amyloid beta (Abeta) and tau
      hyperphosphorylation are involved in mitochondrial dysfunction and synaptic
      damage in AD. Further, recent research also revealed that the protein levels of
      mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1),
      are elevated in the affected regions of AD postmortem brains and cortical tissues
      from APP transgenic mice. In addition, emerging research using AD postmortem
      brains and AD mouse models revealed that VDAC1 is linked to Abeta and
      phosphorylated tau, blocks the mitochondrial permeability transition (MPT) pores,
      disrupts the transport of mitochondrial proteins and metabolites, impairs gating
      of VDAC, and causes defects in oxidative phosphorylation, leading to
      mitochondrial dysfunction in AD neurons. The purpose of this article is to review
      research that has investigated the relationship between VDAC1 and the regulation
      of MPT pores in AD progression.

PMID- 22995653
TI  - Abiraterone acetate for treatment of metastatic castration-resistant prostate
      cancer: final overall survival analysis of the COU-AA-301 randomised, double
      blind, placebo-controlled phase 3 study.
AB  - BACKGROUND: Abiraterone acetate improved overall survival in metastatic
      castration-resistant prostate cancer at a preplanned interim analysis of the COU
      AA-301 double-blind, placebo-controlled phase 3 study. Here, we present the final
      analysis of the study before crossover from placebo to abiraterone acetate (after
      775 of the prespecified 797 death events). METHODS: Between May 8, 2008, and July
      28, 2009, this study enrolled 1195 patients at 147 sites in 13 countries.
      Patients were eligible if they had metastatic castration-resistant prostate
      cancer progressing after docetaxel. Patients were stratified according to
      baseline Eastern Cooperative Oncology Group (ECOG) performance status, worst pain
      over the past 24 h on the Brief Pain Inventory-Short Form, number of previous
      chemotherapy regimens, and type of progression. Patients were randomly assigned
      (ratio 2:1) to receive either abiraterone acetate (1000 mg, once daily and
      orally) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone
      with a permuted block method via an interactive web response system. The primary
      endpoint was overall survival, analysed in the intention-to-treat population.
      This study is registered with ClinicalTrials.gov, number NCT00091442. FINDINGS:
      Of the 1195 eligible patients, 797 were randomly assigned to receive abiraterone
      acetate plus prednisone (abiraterone group) and 398 to receive placebo plus
      prednisone (placebo group). At median follow-up of 20.2 months (IQR 18.4-22.1),
      median overall survival for the abiraterone group was longer than in the placebo
      group (15.8 months [95% CI 14.8-17.0] vs 11.2 months [10.4-13.1]; hazard ratio
      [HR] 0.74, 95% CI 0.64-0.86; p<0.0001). Median time to PSA progression (8.5
      months, 95% CI 8.3-11.1, in the abiraterone group vs 6.6 months, 5.6-8.3, in the
      placebo group; HR 0.63, 0.52-0.78; p<0.0001), median radiologic progression-free
      survival (5.6 months, 5.6-6.5, vs 3.6 months, 2.9-5.5; HR 0.66, 0.58-0.76;
      p<0.0001), and proportion of patients who had a PSA response (235 [29.5%] of 797
      patients vs 22 [5.5%] of 398; p<0.0001) were all improved in the abiraterone
      group compared with the placebo group. The most common grade 3-4 adverse events
      were fatigue (72 [9%] of 791 patients in the abiraterone group vs 41 [10%] of 394
      in the placebo group), anaemia (62 [8%] vs 32 [8%]), back pain (56 [7%] vs 40
      [10%]), and bone pain (51 [6%] vs 31 [8%]). INTERPRETATION: This final analysis
      confirms that abiraterone acetate significantly prolongs overall survival in
      patients with metastatic castration-resistant prostate cancer who have progressed
      after docetaxel treatment. No new safety signals were identified with increased
      follow-up.

PMID- 22995658
TI  - Capturing the multiscale anatomical shape variability with polyaffine
      transformation trees.
AB  - Mandible fractures are classified depending on their location. In clinical
      practice, locations are grouped into regions at different scales according to
      anatomical, functional and esthetic considerations. Implant design aims at
      defining the optimal implant for each patient. Emerging population-based
      techniques analyze the anatomical variability across a population and perform
      statistical analysis to identify an optimal set of implants. Current efforts are
      focused on finding clusters of patients with similar characteristics and
      designing one implant for each cluster. Ideally, the description of anatomical
      variability is directly connected to the clinical regions. This connection is
      what we present here, by introducing a new registration method that builds upon a
      tree of locally affine transformations that describes variability at different
      scales. We assess the accuracy of our method on 146 CT images of femurs. Two
      medical experts provide the ground truth by manually measuring six landmarks. We
      illustrate the clinical importance of our method by clustering 43 CT images of
      mandibles for implant design. The presented method does not require any
      application-specific input, which makes it attractive for the analysis of other
      multiscale anatomical structures. At the core of our new method lays the
      introduction of a new basis for stationary velocity fields. This basis has very
      close links to anatomical substructures. In the future, this method has the
      potential to discover the hidden and possibly sparse structure of the anatomy.

PMID- 22995660
TI  - Optimized design for a novel acetabular component with three wings. A study of
      finite element analysis.
AB  - BACKGROUND: A novel acetabular component with three wings has earlier been
      explored for reconstructing extensive acetabular bone defects in hip revision
      arthroplasty with a satisfying clinical result. However, the periacetabular
      stress patterns and mechanisms by which the acetabular cup obtains initial
      stability are not clear. PURPOSES: The purpose of this study was to evaluate the
      stress patterns of the novel cup using finite element method and possible effects
      of joint loading postoperatively, and to analyze its optimized design for the
      structural parameters of the cup. METHODS: Three-dimensional finite-element (FE)
      models of the cup with three wings and the hemispherical cup were created to
      calculate the stress patterns during a normal gait cycle using FE formulations.
      The stresses of these acetabular components were analyzed and compared. RESULTS:
      FE analysis demonstrated that the cup with three wings and the hemispherical cup
      had the same trend for stress and strain. The stress of the wings increased
      gradually from rim to root. Its peak stress was significantly lower than the
      yield force of the Co-Cr-Mo alloy at the joint between the wing and the shell.
      The graft portion near the acetabular component was subjected to higher stress
      conditions. The contact stresses were found to be decreased with a reduced
      abduction angle of wings and not affected by changed eversion angle of wings. The
      cup with wings of abduction angle of 15 degrees  had lower stresses compared with
      other cups. CONCLUSIONS: The cup with wings is a reliable option for the
      reconstruction of the acetabulum with extensive bone socket defects. The reduced
      abduction angle of wings helps to decrease the stress of the cup with wings.
      However, removing the eversion angle of wings may be the most prudent choice to
      avoid the introduction of adverse variables, which may contribute to the
      loosening of the acetabular component. FE analysis is a useful tool with which to
      address these issues.

PMID- 22995659
TI  - Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related
      complex II deficiency.
AB  - BACKGROUND: Deficiency of complex II (succinate dehydrogenase, SDH) represents a
      rare cause of mitochondrial disease and is associated with a wide range of
      clinical symptoms. Recently, mutations of SDHAF1, the gene encoding for the SDH
      assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy.
      Our goal was to identify SDHAF1 mutations in further patients and to delineate
      the clinical phenotype. METHODS: In a retrospective data collection study we
      identified nine children with biochemically proven complex II deficiency among
      our cohorts of patients with mitochondrial disorders. The cohort comprised five
      patients from three families affected by SDH-defective infantile
      leukoencephalopathy with accumulation of succinate in disordered cerebral white
      matter, as detected by in vivo proton MR spectroscopy. One of these patients had
      neuropathological features of Leigh syndrome. Four further unrelated patients of
      the cohort showed diverse clinical phenotypes without leukoencephalopathy. SDHAF1
      was sequenced in all nine patients. RESULTS: Homozygous mutations of SDHAF1 were
      detected in all five patients affected by leukoencephalopathy with accumulated
      succinate, but not in any of the four patients with other, diverse clinical
      phenotypes. Two sisters had a mutation reported previously, in three patients two
      novel mutations were found. CONCLUSION: Leukoencephalopathy with accumulated
      succinate is a key symptom of defective complex II assembly due to SDHAF1
      mutations.

PMID- 22995661
TI  - TNF-alpha decreases infection-induced lung injury in burn through negative
      regulation of TLR4/iNOS.
AB  - BACKGROUND: Sepsis is an infectious process-induced generalized inflammatory
      response that mediates the excessive production of cytokines. However, anti-tumor
      necrosis factor (TNF)-alpha therapy has failed in decreasing mortality of sepsis
      patients due to undefined mechanisms. This study was designed to investigate
      whether absence of TNF receptor enhanced lung damage and mortality through toll
      like receptors (TLRs) and inducible nitric oxide synthase (iNOS). MATERIALS AND
      METHODS: We injected Pseudomonas aeruginosa or lipopolysaccharide in the backs of
      wild-type, Tnfrsf1a(-/-) (deficient of TNF-alpha receptor 1), and TLR4(-/-) mice
      at 8 h after 30% total body surface area burn. The animals were sacrificed at 16
      h after burn and lung tissues were harvested and examined for determining
      pulmonary microvascular dysfunction and interleukin (IL)-1beta, iNOS, and TLR4
      expression. The blood of animals was harvested for bacterial count assay. The
      effect of S-methylisothiourea, an iNOS inhibitor, on P aeruginosa infection with
      thermal injury pretreatment-induced lung damage was also examined. RESULTS: P
      aeruginosa or lipopolysaccharide injection with thermal injury pretreatment
      enhanced TLR4, iNOS, and IL-1beta expression and pulmonary microvascular
      dysfunction in Tnfrsf1a(-/-) mice compared with wild-type mice. P aeruginosa
      infection with thermal injury pretreatment did not induce IL-1beta or iNOS
      expression and mortality in TLR4(-/-) mice. S-methylisothiourea treatment
      significantly decreased P aeruginosa infection with thermal injury pretreatment
      induced lung injury, blood bacterial counts, pulmonary IL-1beta expression, and
      mortality in Tnfrsf1a(-/-) mice. CONCLUSIONS: Given that absence of the TNF-alpha
      receptor 1 is associated with increased lung permeability, we conclude that TNF
      alpha decreases P aeruginosa infection-induced lung damage in burn mice through
      negative regulation of TLR4 as well as iNOS expression, and iNOS inhibitor might
      be useful in reversing anti-TNF-alpha therapy-induced lung injury in burn.

PMID- 22995662
TI  - Evaluating swallowing muscles essential for hyolaryngeal elevation by using
      muscle functional magnetic resonance imaging.
AB  - PURPOSE: Reduced hyolaryngeal elevation, a critical event in swallowing, is
      associated with radiation therapy. Two muscle groups that suspend the hyoid,
      larynx, and pharynx have been proposed to elevate the hyolaryngeal complex: the
      suprahyoid and longitudinal pharyngeal muscles. Thought to assist both groups is
      the thyrohyoid, a muscle intrinsic to the hyolaryngeal complex. Intensity
      modulated radiation therapy guidelines designed to preserve structures important
      to swallowing currently exclude the suprahyoid and thyrohyoid muscles. This study
      used muscle functional magnetic resonance imaging (mfMRI) in normal healthy
      adults to determine whether both muscle groups are active in swallowing and to
      test therapeutic exercises thought to be specific to hyolaryngeal elevation.
      METHODS AND MATERIALS: mfMRI data were acquired from 11 healthy subjects before
      and after normal swallowing and after swallowing exercise regimens (the
      Mendelsohn maneuver and effortful pitch glide). Whole-muscle transverse
      relaxation time (T2 signal, measured in milliseconds) profiles of 7 test muscles
      were used to evaluate the physiologic response of each muscle to each condition.
      Changes in effect size (using the Cohen d measure) of whole-muscle T2 profiles
      were used to determine which muscles underlie swallowing and swallowing
      exercises. RESULTS: Post-swallowing effect size changes (where a d value of >0.20
      indicates significant activity during swallowing) for the T2 signal profile of
      the thyrohyoid was a d value of 0.09; a d value of 0.40 for the mylohyoid, 0.80
      for the geniohyoid, 0.04 for the anterior digastric, and 0.25 for the posterior
      digastric-stylohyoid in the suprahyoid muscle group; and d values of 0.47 for the
      palatopharyngeus and 0.28 for the stylopharyngeus muscles in the longitudinal
      pharyngeal muscle group. The Mendelsohn maneuver and effortful pitch glide
      swallowing exercises showed significant effect size changes for all muscles
      tested, except for the thyrohyoid. CONCLUSIONS: Muscles of both the suprahyoid
      and the longitudinal pharyngeal muscle groups are active in swallowing, and both
      swallowing exercises effectively target muscles elevating the hyolaryngeal
      complex. mfMRI is useful in testing swallowing muscle function.

PMID- 22995663
TI  - Bile acid malabsorption after pelvic and prostate intensity modulated radiation
      therapy: an uncommon but treatable condition.
AB  - PURPOSE: Intensity modulated radiation therapy (IMRT) is a significant
      therapeutic advance in prostate cancer, allowing increased tumor dose delivery
      and increased sparing of normal tissues. IMRT planning uses strict dose
      constraints to nearby organs to limit toxicity. Bile acid malabsorption (BAM) is
      a treatable disorder of the terminal ileum (TI) that presents with symptoms
      similar to radiation therapy toxicity. It has not been described in patients
      receiving RT for prostate cancer in the contemporary era. We describe new-onset
      BAM in men after IMRT for prostate cancer. METHODS AND MATERIALS: Diagnosis of
      new-onset BAM was established after typical symptoms developed, selenium-75
      homocholic acid taurine (SeHCAT) scanning showed 7-day retention of <15%, and
      patients' symptoms unequivocally responded to a bile acid sequestrant. The TI was
      identified on the original radiation therapy plan, and the radiation dose
      delivered was calculated and compared with accepted dose-volume constraints.
      RESULTS: Five of 423 men treated in a prospective series of high-dose prostate
      and pelvic IMRT were identified with new onset BAM (median age, 65 years old).
      All reported having normal bowel habits before RT. The volume of TI ranged from
      26-141 cc. The radiation dose received by the TI varied between 11.4 Gy and 62.1
      Gy (uncorrected). Three of 5 patients had TI treated in excess of 45 Gy
      (equivalent dose calculated in 2-Gy fractions, using an alpha/beta ratio of 3)
      with volumes ranging from 1.6 cc-49.0 cc. One patient had mild BAM (SeHCAT
      retention, 10%-15%), 2 had moderate BAM (SeHCAT retention, 5%-10%), and 2 had
      severe BAM (SeHCAT retention, <5%). The 3 patients whose TI received >=45 Gy
      developed moderate to severe BAM, whereas those whose TI received <45 Gy had only
      mild to moderate BAM. CONCLUSIONS: Radiation delivered to the TI during IMRT may
      cause BAM. Identification of the TI from unenhanced RT planning computed
      tomography scans is difficult and may impede accurate dosimetric evaluation.
      Thorough toxicity assessment and close liaison between oncologist and
      gastroenterologist allow timely diagnosis and treatment.

PMID- 22995664
TI  - Congratulations to team GB, but why should we be so surprised? Olympic medal
      count can be predicted using logit regression models that include 'home
      advantage'.

PMID- 22995665
TI  - Putting your money where your mouth is: parents' valuation of good oral health of
      their children.
AB  - The aim of this study was to investigate the parental willingness to invest in
      good oral health for their child in terms of money and time and to relate this to
      oral health related knowledge and behavioral aspects. 290 parents of 6-year-old
      children, participating in a RCT on caries preventive strategies in The
      Netherlands were asked to provide information on education, oral health habits,
      dietary habits, knowledge on dental topics, willingness to pay and perceived
      resistance against investing in preventive oral health actions for their
      children. Despite the fact that parents overall valued oral health for their
      child highly, still 12% of the parents were unwilling to spend any money, nor to
      invest any time by brushing their children's teeth to maintain good oral health
      for their child. Additionally, they indicated that they were unwilling to visit
      the dentist for preventive measures more than once a year. These children may
      certainly be considered at higher risk of developing oral diseases because worse
      oral hygiene habits and dietary habits were found in this group. Given the
      results, it may be necessary to differentiate in allocating caries prevention
      programmes to target parents or (school-based) children directly.

PMID- 22995666
TI  - The relationship between mortality and time since divorce, widowhood or
      remarriage in Norway.
AB  - The chance of dying within any given year probably depends not only on marital
      status in that year but also on earlier partnership history. There is still not
      much knowledge about such effects, however. Our intention is to see how mortality
      is associated with time since divorce, bereavement and remarriage and time
      between marital disruption and remarriage. We use register data that include the
      entire Norwegian population aged 40-89 from 1970 to 2008 (70,701,767 person-years
      of exposure and 1,484,281 deaths). The excess mortality of divorced men compared
      to their married counterparts increases with time since divorce, while there is
      no such trend among divorced women. The pattern is opposite for the widowed,
      among whom there are indications of a more sharply positive association with time
      since bereavement for women than for men, though the association is rather weak
      for both sexes. The remarried have higher mortality than the first-time married,
      with one surprising exception: men who have remarried after a period of less than
      10 years as divorced or widowed have the same mortality as the married. There is
      no clear association between mortality and time since remarriage. We discuss
      possible reasons for these patterns.

PMID- 22995668
TI  - Indifferent to disease: a qualitative investigation of the reasons why some Papua
      New Guineans who own mosquito nets choose not to use them.
AB  - This paper presents findings from a qualitative study designed to explore the
      reasons why some Papua New Guineans who own mosquito nets choose not to use them,
      whether on a regular or episodic basis. In-depth interviews (IDIs) were conducted
      with a sub-sample (n = 44) of participants in a country wide household survey who
      reported owning or having access to a mosquito net, but not having slept under a
      mosquito net the night prior to survey. All IDIs were completed between December
      2010 and June 2011. Analysis was informed by a general inductive methodology.
      Multiple impediments to regular mosquito net use were identified by study
      participants, although all were broadly grouped into the inter-related categories
      of net-, environmental- or human-factors. Indifference emerged as the most
      influential impediment towards regular net use presenting as a general
      attitudinal context in which a majority of participant responses were grounded. A
      lack of knowledge regarding malaria transmission pathways or the utility of
      mosquito nets did not appear to underlie this indifference. Rather, the
      indifference appeared to be rooted in a lack of fear of malaria infection
      cultivated through lived experience. A wide range of interventions could
      potentially promote greater mosquito net use amongst this population. However,
      the basis of any intervention strategy, given the pervasive indifferent attitude
      towards regular mosquito net use, should be to render individual mosquito net use
      as easy and as convenient as possible and to promote complementary malaria
      control strategies where appropriate.

PMID- 22995667
TI  - Aggravating conditions: cynical hostility and neighborhood ambient stressors.
AB  - This study is the first to investigate neighborhood clustering of a personality
      trait--cynical hostility (a sense of mistrust of others amplified by suspicious
      antagonism.) Cynical hostility increases physiological reactivity by influencing
      appraisal and coping when stressful events occur and that has been well
      established as a predictor of cardiovascular disease, inflammation, and all-cause
      mortality. The analysis examines the associations of a variety of neighborhood
      physical and social conditions (especially ambient stressors) with individual
      cynical hostility, controlling for individual sociodemographics. Data are from
      the Chicago Community Adult Health Survey, a clustered population-based study of
      3105 adults. Variation by neighborhood in cynical hostility is larger than
      variation of other selected health outcomes, which are commonly studied using
      ecological methods or for other personality measures. Controlling for
      neighborhood context reduces the black/white cynical hostility disparity by one
      third. A measure of neighborhood ambient stressors (notably noise) significantly
      predicts cynical hostility, even after individual characteristics are controlled,
      and the effect size is larger than for other contextual predictors. Health
      related psychosocial and personality traits may both cluster in and be influenced
      by contemporaneous neighborhoods rather than mere exogenous results of genes or
      early life conditions. Health-relevant psychosocial characteristics may also
      mediate effects of neighborhood deleterious physical conditions, thereby
      influencing downstream health outcomes and social disparities therein. Because
      residential location and neighborhood physical conditions are both modifiable,
      research on how ambient stressors influence health psychology may be particularly
      fruitful for health policy and practice.

PMID- 22995669
TI  - Jejunal free flap reconstruction of the pharyngolaryngectomy defect: 368
      consecutive cases.
AB  - BACKGROUND: The Jejunal Free Flap (JFF) was first described by Seidenberg in 1957
      for the reconstruction of pharyngolryngectomy defects. Historically, its outcome
      profile has been better than alternative reconstructions. Recently, the use of
      tubed Fasciocutaneous Free Flaps (FCFF) has been increasing as series reporting
      outcomes superior or equivalent to JFF are published. Our experience with JFF has
      been more positive than recently published reports suggest. This study aims to
      provide an accurate and up-to-date assessment of outcomes in JFF reconstruction
      of pharyngolaryngectomy defects and to compare these results to those of
      contemporary alternative techniques. METHODS: 368 Consecutive free jejunum
      reconstructions were performed for pharyngolaryngectomy defects between 1977 and
      2010. All patients had been assessed by a multidisciplinary Head and Neck Clinic
      prior to surgery. A systematic review of recent literature pertaining to
      pharyngolaryngectomy reconstruction outcomes was undertaken for comparison with
      our dataset. RESULTS: 70.9% of tumours in this series were T-grade 3 or 4.
      Perioperative mortality was 3.8% and flap failure occurred in 2.98%. The
      incidence of anastomotic leak was 8.2% and stricture occurred in 10.9%. A full
      oral diet was maintained by 91.6% of patients by day 12 on average. 70.6%
      underwent primary tracheo-oesophageal puncture and of these 78.1% had effective
      speech. CONCLUSIONS: Overall, our data compares favourably with other series. The
      strengths of the JFF reconstruction are the capacity to maintain an oral diet,
      low stricture and leak rates and the versatility to reconstruct long segment
      defects. We have observed variability in leak rates throughout the study period,
      which may be operator dependant. The gap between outcomes for FCFF and JFF
      reconstructions has narrowed but the latter remains our reconstruction of choice
      for pharyngolaryngectomy defects.

PMID- 22995671
TI  - Self-harm behaviour: rethinking physical and mental health.

PMID- 22995670
TI  - Premature death after self-harm: a multicentre cohort study.
AB  - BACKGROUND: People who self-harm have an increased risk of premature death. The
      aim of this study was to investigate cause-specific premature death in
      individuals who self-harm, including associations with socioeconomic deprivation.
      METHODS: We undertook a cohort study of patients of all ages presenting to
      emergency departments in Oxford, Manchester, and Derby, UK, after self-poisoning
      or self-injury between Jan 1, 2000, and Dec 31, 2007. Postcodes of individuals'
      place of residence were linked to the Index of Multiple Deprivation 2007 in
      England. Mortality information was supplied by the Medical Research Information
      Service of the National Health Service. Patients were followed up to the end of
      2009. We calculated age-standardised mortality ratios (SMRs) and years of life
      lost (YLL), and we tested for associations with socioeconomic deprivation.
      FINDINGS: 30 950 individuals presented with self-harm and were followed up for a
      median of 6.0 years (IQR 3.9-7.9). 1832 (6.1%) patients died before the end of
      follow-up. Death was more likely in patients than in the general population (SMR
      3.6, 95% CI 3.5-3.8), and occurred more in males (4.1, 3.8-4.3) than females
      (3.2, 2.9-3.4). Deaths due to natural causes were 2-7.5 times more frequent than
      was expected. For individuals who died of any cause, mean YLL was 31.4 years (95%
      CI 30.5-32.2) for male patients and 30.7 years (29.5-31.9) for female patients.
      Mean YLL for natural-cause deaths was 25.9 years (25.7-26.0) for male patients
      and 25.5 years (25.2-25.8) for female patients, and for external-cause deaths was
      40.2 years (40.0-40.3) and 40.0 years (39.7-40.5), respectively. Disease of the
      circulatory (13.1% in males; 13.0% in females) and digestive (11.7% in males;
      17.8% in females) systems were major contributors to YLL from natural causes. All
      cause mortality increased with each quartile of socioeconomic deprivation in male
      patients (chi(2) trend 39.6; p<0.0001), female patients (13.9; p=0.0002), and
      both sexes combined (55.4; p<0.0001). Socioeconomic deprivation was related to
      mortality in both sexes combined from natural causes (51.0; p<0.0001) but not
      from external causes (0.30; p=0.58). Alcohol problems were associated with death
      from digestive-system disease, drug misuse with mental and behavioural disorders,
      and physical health problems with circulatory-system disease. INTERPRETATION:
      Physical health and life expectancy are severely compromised in individuals who
      self-harm compared with the general population. In the management of self-harm,
      clinicians assessing patients' psychosocial problems should also consider their
      physical needs. FUNDING: Department of Health Policy Research Programme.

PMID- 22995672
TI  - Plasma morphine and metabolite concentrations are associated with clinical
      effects of morphine in cancer patients.
AB  - CONTEXT: Morphine is the opioid of choice for cancer-related pain, but for many
      patients the benefits of morphine are outweighed by its side effect profile.
      Morphine is metabolized to morphine-3-glucuronide and morphine-6-glucuronide;
      however, little is known about the contribution of these metabolites to analgesia
      and morphine-related side effects. OBJECTIVES: We investigated the association
      between plasma morphine and metabolite concentrations and the clinical effects of
      morphine in cancer patients. METHODS: A prospective study was performed in cancer
      patients taking oral morphine for moderate-to-severe cancer pain. Subjects who
      responded well to morphine (responders) and subjects who failed to respond to
      morphine because of lack of analgesia and/or the presence of intolerable side
      effects (nonresponders/switchers) were recruited. Pain and toxicity scores were
      recorded and blood samples were analyzed for plasma morphine, morphine-3
      glucuronide, and morphine-6-glucuronide concentrations. RESULTS: Results showed
      that 1) morphine responders have higher plasma morphine and metabolite
      concentrations compared with nonresponders, 2) lower pain scores are associated
      with higher plasma morphine and metabolite concentrations, 3) central side
      effects are associated with a higher metabolite:plasma morphine ratio, and 4)
      myoclonus is associated with extremely high concentrations of plasma morphine and
      metabolites. CONCLUSION: This study has shown that plasma morphine and metabolite
      concentrations are associated with the clinical effects of morphine therapy.
      These results are important because they demonstrate the relevance of measuring
      plasma metabolite concentrations in clinical trials and the potential for
      metabolite data to deepen our understanding of factors that influence an
      individual's response to morphine.

PMID- 22995674
TI  - WITHDRAWN: The Endoplasmic Reticulum Stress Response Activates Tissue
      Transglutaminase and Intestinal Inflammation by Reducing Levels of IkappaBalpha
AB  - This article has been withdrawn at the request of the authors. 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- 22995673
TI  - Efficacy and tolerability of a novel herbal formulation for weight management in
      obese subjects: a randomized double blind placebo controlled clinical study.
AB  - BACKGROUND: The effect of an herbal formulation LI85008F on weight loss in obese
      human subjects was evaluated in an 8-weeks randomized, double-blind, placebo
      controlled study (Clinical Trial Registration no. ISRCTN37381706). Fifty obese
      subjects (Body mass index 30 to 40 kg/m2, 29.3% male; 70.7% female; ages 27-50
      years) were randomized into two groups; placebo (n = 25) and LI85008F formulation
      (n = 25). The participants received either 900 mg/day of LI85008F formulation in
      three divided doses or three identical placebo capsules and all of them remained
      on a calorie-controlled diet (2000 cal/day) and 30 min walking for 5 days a week
      during the entire duration of the study. RESULTS AND DISCUSSION: At the end of
      the trial period, LI85008F supplemented group showed significant net reductions
      in body weight and Body Mass Index (BMI). The participants who received the
      herbal formulation, showed reduced fasting blood glucose, LDL, LDL/HDL ratio, and
      triglycerides. At the end of the study, LI85008F supplementation also provided
      21.26% (p = 0.012) increase in serum adiponectin level, compared with the placebo
      group. No major adverse events were reported by the participants in the study
      duration. In addition, Adipokine profiling study in 3T3-L1 adipocytes
      demonstrates that LI85008F modulates key regulatory factors of adipogenic
      differentiation and insulin sensitivity, such as Adiponectin, Pref-1, and
      resistin. CONCLUSION: The herbal formulation LI85008F (Adipromin) is prepared
      from commonly used medicinal plants extracts, which provides useful and safe
      application for weight loss in obese humans. It also demonstrates potential
      promise in controlling healthy blood glucose level in obesity linked type 2
      diabetes.

PMID- 22995676
TI  - Identification and molecular characterization of a novel antigen of Eimeria
      acervulina.
AB  - Eimeria acervulina (E. acervulina) is one of the seven species of Eimeria
      infected in chicken. Until now, only a few antigen genes of E. acervulina have
      been reported. In this study, a cDNA expression library of E. acervulina
      sporozoites was constructed in a eukaryotic expression vector, pVAX1.0.
      Subsequently, the library was divided into pools and inoculated into chickens to
      observe the ability of the antigens to induce humoral immune response and cell
      mediated immune response. The positive pools that stimulated significant immune
      responses were fractionated sequentially until a single positive clone was
      screened. After three rounds of screening, a clone, named as cSZ-JN1, with the
      ability to stimulate chicken immune response was obtained. The sequence analysis
      showed that the opening reading fragment (ORF) of cSZ-JN1 was 615 bp in size and
      encoded a predicted protein of 204 amino acids with 21.8 kDa. BLASTN and other
      sequence databases searches revealed that the identity of the amino acid sequence
      of cSZ-JN1 to the complete sequence of Eimeria tenella annotated protein
      (ETH_00022005.1.pep) was 31.37% and to Toxoplasma gondii ME49 hypothetical
      protein (gb|EEB00972.1|) 24%, and had no significant homology with the known
      genes of E. acervulina and other parasites. Immunofluorescence analysis using
      antibody against recombinant cSZ-JN1 indicated that this protein was expressed in
      sporozoite and merozoite development stages. Animal challenge experiments
      demonstrated that the recombinant protein of cSZ-JN1 and DNA vaccine carrying cSZ
      JN1 could significantly increase the average body weight gains, decrease the mean
      lesion scores and the oocyst outputs of the immunized chickens and presented anti
      coccidial index more than 160. All the above results suggested that the cSZ-JN1
      was a novel E. acervulina antigen and could be an effective candidate for the
      development of new vaccine against E. acervulina infection.

PMID- 22995675
TI  - The effects of vertical sleeve gastrectomy in rodents are ghrelin independent.
AB  - Reductions in levels of the hunger-stimulating hormone ghrelin have been proposed
      to mediate part of the effects of vertical sleeve gastrectomy (VSG) and Roux-en-Y
      gastric bypass surgeries for obesity. We studied circulating levels of acyl and
      desacyl ghrelin in rats after these surgeries. We found that blood levels of
      ghrelin were reduced after VSG, but not after Roux-en-Y gastric bypass, based on
      enzyme-linked immunosorbent assay and mass-spectrometry analyses. We compared the
      effects of VSG in ghrelin-deficient mice and wild-type mice on food intake, body
      weight, dietary fat preference, and glucose tolerance. We found that VSG produced
      comparable outcomes in each strain. Reduced ghrelin signaling therefore does not
      appear to be required for these effects of VSG.

PMID- 22995677
TI  - School feeding, moving from practice to policy: reflections on building
      sustainable monitoring and evaluation systems.
AB  - OBJECTIVE: To provide an overview of the status of monitoring and evaluation
      (M&E) of school feeding across sub-Saharan Africa and to reflect on the
      experience on strengthening M&E systems to influence policy making in low-income
      countries. DESIGN: Literature review on the M&E of school feeding programmes as
      well as data from World Food Programme surveys. SETTING: Sub-Saharan Africa.
      SUBJECTS: Countries implementing school feeding. RESULTS: Only two randomized
      controlled impact evaluations have been implemented in sub-Saharan Africa. Where
      M&E data collection is underway, the focus is on process and service delivery and
      not on child outcomes. M&E systems generally operate under the Ministry of
      Education, with other Ministries represented within technical steering groups
      supporting implementation. There is no internationally accepted standardized
      framework for the M&E of school feeding. There have been examples where evidence
      of programme performance has influenced policy: considering the popularity of
      school feeding these cases though are anecdotal, highlighting the opportunity for
      systemic changes. CONCLUSIONS: There is strong buy-in on school feeding from
      governments in sub-Saharan Africa. In response to this demand, development
      partners have been harmonizing their support to strengthen national programmes,
      with a focus on M&E. However, policy processes are complex and can be influenced
      by a number of factors. A comprehensive but simple approach is needed where the
      first step is to ensure a valid mandate to intervene, legitimizing the
      interaction with key stakeholders, involving them in the problem definition and
      problem solving. This process has been facilitated through the provision of
      technical assistance and exposure to successful experiences through South-South
      cooperation and knowledge exchange.

PMID- 22995678
TI  - Simultaneous determination of moxifloxacin and cefixime by first and ratio first
      derivative ultraviolet spectrophotometry.
AB  - BACKGROUND: The new combination of moxifloxacin HCl and cefixime trihydrate is
      approved for the treatment of lower respiratory tract infections in adults. At
      initial formulation development and screening stage a fast and reliable method
      for the dissolution and release testing of moxifloxacin and cefixime were highly
      desirable. The zero order overlaid UV spectra of moxifloxacin and cefixime showed
      >90% overlapping. Hence, simple, accurate precise and validated two derivative
      spectrophotometric methods have been developed for the determination of
      moxifloxacin and cefixime. METHODS: In the first derivative spectrophotometric
      method varying concentration of moxifloxacin and cefixime were prepared and
      scanned in the range of 200 to 400 nm and first derivative spectra were
      calculated (n = 1). The zero crossing wavelengths 287 nm and 317.9 nm were
      selected for determination of moxifloxacin and cefixime, respectively. In the
      second method the first derivative of ratio spectra was calculated and used for
      the determination of moxifloxacin and cefixime by measuring the peak intensity at
      359.3 nm and 269.6 nm respectively. RESULTS: Calibration graphs were established
      in the range of 1-16 MUg /mL and 1-15 MUg /mL for both the drugs by first and
      ratio first derivative spectroscopic methods respectively with good correlation
      coefficients. Average accuracy of assay of moxifloxacin and cefixime were found
      to be 100.68% and 98 93%, respectively. Relative standard deviations of both
      inter and intraday assays were less than 1.8%. Moreover, recovery of moxifloxacin
      and cefixime was more than 98.7% and 99.1%, respectively. CONCLUSIONS: The
      described derivative spectrophotometric methods are simple, rapid, accurate,
      precise and excellent alternative to sophisticated chromatographic techniques.
      Hence, the proposed methods can be used for the quality control of the cited
      drugs and can be extended for routine analysis of the drugs in formulations.

PMID- 22995679
TI  - Reflex epilepsy induced by playing Go-stop or Baduk games.
AB  - PURPOSE: Seizures can be triggered by complex mental activities. The aim of this
      study was to investigate the clinical characteristics of reflex epilepsy induced
      by playing Go-stop or Baduk games. METHODS: The study comprised 11 patients with
      this type of reflex epilepsy identified from our patient database. We collected
      data on clinical features, EEG, and brain MRI as well as seizure outcomes.
      RESULTS: The patients had a late age of onset (range, 43-65 years, except for one
      patient with an age of onset of 11 years). An MRI abnormality and interictal EEG
      abnormalities were found in one patient respectively. The seizures exhibited
      diverse semiological features suggesting a focal or generalized onset. No
      myoclonic seizures were observed. Individualized strategies such as avoiding the
      precipitating game or reducing exposure to the stimulus were most effective in
      preventing the seizures. CONCLUSION: The pathophysiological mechanisms underlying
      Go-stop- or Baduk-induced seizures may be different from other cognition
      associated reflex epileptic phenomena. This type of reflex epilepsy may be a
      heterogeneous syndrome manifesting in a range of diverse semiological features.

PMID- 22995680
TI  - Computational models of epilepsy.
AB  - PURPOSE: Approximately 30% of epilepsy patients suffer from medically refractory
      epilepsy, in which seizures can not controlled by the use of anti-epileptic drugs
      (AEDs). Understanding the mechanisms underlying these forms of drug-resistant
      epileptic seizures and the development of alternative effective treatment
      strategies are fundamental challenges for modern epilepsy research. In this
      context, computational modeling has gained prominence as an important tool for
      tackling the complexity of the epileptic phenomenon. In this review article, we
      present a survey of computational models of epilepsy from the point of view that
      epilepsy is a dynamical brain disease that is primarily characterized by
      unprovoked spontaneous epileptic seizures. METHOD: We introduce key concepts from
      the mathematical theory of dynamical systems, such as multi-stability and
      bifurcations, and explain how these concepts aid in our understanding of the
      brain mechanisms involved in the emergence of epileptic seizures. RESULTS: We
      present a literature survey of the different computational modeling approaches
      that are used in the study of epilepsy. Special emphasis is placed on
      highlighting the fine balance between the degree of model simplification and the
      extent of biological realism that modelers seek in order to address relevant
      questions. In this context, we discuss three specific examples from published
      literature, which exemplify different approaches used for developing
      computational models of epilepsy. We further explore the potential of recently
      developed optogenetics tools to provide novel avenue for seizure control.
      CONCLUSION: We conclude with a discussion on the utility of computational models
      for the development of new epilepsy treatment protocols.

PMID- 22995681
TI  - In vivo imaging of retinal ganglion cell apoptosis.
AB  - Apoptosis, or programmed cell death, plays a vital role in normal development and
      ageing. However, dysregulation of this process is responsible for many disease
      states including; cancer, autoimmune and neurodegeneration. For this reason, in
      vivo visualisation of apoptosis may prove a useful tool for both laboratory
      research and clinical diagnostics. Glaucoma comprises a distinctive group of
      chronic optic neuropathies, characterised by the progressive loss of retinal
      ganglion cells (RGCs). Early diagnosis of glaucoma remains a clear and unmet
      need. Recently, there have been significant advances in the detection of
      apoptosis in vivo using fluorescent probes to visualise single RGCs undergoing
      apoptosis, specifically DARC (Detection of Apoptotic Retinal Cells) [1] and capQ
      technology [2(**)].

PMID- 22995682
TI  - [Paradoxical embolism via a patent foramen ovale in the Emergency Department].

PMID- 22995683
TI  - Increased prevalence, incidence, and female predominance of multiple sclerosis in
      northern Japan.
AB  - OBJECTIVE: To carry out the third epidemiologic surveillance of multiple
      sclerosis (MS) in Tokachi province, on the northernmost island of Japan, and to
      compare the results of the present survey on the prevalence, incidence, and
      characteristics of MS and neuromyelitis optica (NMO) with those of previous
      surveys performed in 2001 and 2006. METHODS: A data processing sheet was sent to
      all MS-related institutions in Tokachi province, and all sheets were collected in
      March 2011. The criteria of Poser were used for diagnosing MS and the criteria
      proposed by Wingerchuk for diagnosing NMO. We then compared the results of the
      present survey with those of previous surveys performed in 2001 and 2006 in the
      same community. RESULTS: Fifty-seven patients diagnosed with MS according to the
      criteria of Poser were identified. The prevalence was 16.2/100,000 in 2011, which
      was higher than in the previous studies. The female/male ratio of MS was 2.63,
      2.75, and 3.38 in 2001, 2006, and 2011, respectively. Three patients fulfilled
      the criteria for diagnosis of NMO in 2011; the prevalence of NMO was 0.9/100,000.
      CONCLUSIONS: The results of this study suggest that the prevalence and the female
      predominance of MS have been increasing, due to an increase in the incidence
      after 1990, and that the prevalence of NMO is relatively low in northern Japan.

PMID- 22995684
TI  - Setting new standards in multiple sclerosis care and research.

PMID- 22995685
TI  - Clinical stratification of subtypes of Alzheimer's disease.

PMID- 22995688
TI  - Differences in cerebrogenic cardiac disturbance in men and women.

PMID- 22995689
TI  - Size isn't everything, comparatively speaking.

PMID- 22995690
TI  - Xavier Montalban: a pioneer in understanding multiple sclerosis.

PMID- 22995693
TI  - The myotonic dystrophies: molecular, clinical, and therapeutic challenges.
AB  - Myotonic dystrophy is the most common type of muscular dystrophy in adults and is
      characterised by progressive myopathy, myotonia, and multiorgan involvement. Two
      genetically distinct entities have been identified. Myotonic dystrophy type 1
      (also known as Steinert's disease) was first described more than 100 years ago,
      whereas myotonic dystrophy type 2 was identified only 18 years ago, after genetic
      testing for type 1 disease could be applied. Both diseases are caused by
      autosomal dominant nucleotide repeat expansions. In patients with myotonic
      dystrophy type 1, a (CTG)(n) expansion is present in DMPK, whereas in patients
      with type 2 disease, there is a (CCTG)(n) expansion in CNBP. When transcribed
      into CUG-containing RNA, mutant transcripts aggregate as nuclear foci that
      sequester RNA-binding proteins, resulting in a spliceopathy of downstream
      effector genes. The prevailing paradigm therefore is that both disorders are
      toxic RNA diseases. However, research indicates several additional pathogenic
      effects take place with respect to protein translation and turnover. Despite
      clinical and genetic similarities, myotonic dystrophy type 1 and type 2 are
      distinct disorders requiring different diagnostic and management strategies.

PMID- 22995694
TI  - Reversible cerebral vasoconstriction syndrome.
AB  - Recurrent thunderclap headaches, seizures, strokes, and non-aneurysmal
      subarachnoid haemorrhage can all reveal reversible cerebral vasoconstriction
      syndrome. This increasingly recognised syndrome is characterised by severe
      headaches, with or without other symptoms, and segmental constriction of cerebral
      arteries that resolves within 3 months. Reversible cerebral vasoconstriction
      syndrome is supposedly due to a transient disturbance in the control of
      cerebrovascular tone. More than half the cases occur post partum or after
      exposure to adrenergic or serotonergic drugs. Manifestations have a uniphasic
      course, and vary from pure cephalalgic forms to rare catastrophic forms
      associated with several haemorrhagic and ischaemic strokes, brain oedema, and
      death. Diagnosis can be hampered by the dynamic nature of clinicoradiological
      features. Stroke can occur a few days after initial normal imaging, and cerebral
      vasoconstriction is at a maximum on angiograms 2-3 weeks after clinical onset.
      The calcium channel blocker nimodipine seems to reduce thunderclap headaches
      within 48 h of administration, but has no proven effect on haemorrhagic and
      ischaemic complications.

PMID- 22995695
TI  - Diagnosis, disease course, and management of patients with Kleine-Levin syndrome.
AB  - Kleine-Levin syndrome is a rare sleep disorder that mainly affects adolescents
      and is characterised by relapsing-remitting episodes of severe hypersomnia,
      cognitive impairment, apathy, derealisation, and psychiatric and behavioural
      disturbances. Boys are more frequently affected than girls. Just over half of
      patients have hyperphagia, are hypersexual (mainly boys), or have depressed mood
      (mainly girls), and 30% become anxious, delusional, and have hallucinations.
      Although some symptoms are similar to those in patients with encephalopathy,
      imaging and laboratory findings are unremarkable. The first episode of
      hypersomnia is often triggered by an infection, with relapses occurring every 1
      12 months for a median of 14 years; disease duration can be much longer with
      childhood or adult onset than in patients with adolescent onset. Between
      episodes, patients generally have normal sleep patterns, cognition, mood, and
      eating habits. During episodes, electroencephalography might show diffuse or
      local slow activity. Functional imaging studies have revealed hypoactivity in
      thalamic and hypothalamic regions, and in the frontal and temporal lobes.
      Stimulants and mood stabilisers can be beneficial in the treatment of severe
      cases.

PMID- 22995696
TI  - Dentofacial deformities are associated with lower degrees of self-esteem and
      higher impact on oral health-related quality of life: results from an
      observational study involving adults.
AB  - PURPOSE: Patients with dentofacial deformities tend to show poorer oral health
      related quality of life, but few studies thus far have focused on this topic.
      Therefore, the objectives of this study were to evaluate oral health-related
      quality of life, self-esteem, and depression in patients with Class II and Class
      III dentofacial deformities before orthodontic treatment and to compare these
      patients with controls with harmonic faces. MATERIALS AND METHODS: This
      observational, cross-sectional study compared 2 groups (experimental vs control)
      of patients recruited at an outpatient orthodontic clinic. Oral health-related
      quality of life was assessed using a short form of the Oral Health Impact
      Profile, self-esteem was evaluated with the Rosenberg Self-Esteem Scale, and
      depression symptoms were assessed using the General Hospital Depression Scale
      (outcome variables). The presence of dentofacial deformities (ie, group
      allocation) was the primary predictor variable. The chi(2) test and Spearman
      correlation coefficient were used to analyze data. RESULTS: The total sample was
      composed of 68 individuals (34 in each group). In the experimental group, 55.9%
      of patients were women, and 88.2% presented a Class III occlusal relation. The
      mean age in the experimental group was 27.56 years. Significant differences were
      observed between the 2 groups in oral health-related quality of life (P < .001)
      and self-esteem (P < .019), but no differences were found for depression (P =
      .161). CONCLUSIONS: Patients with dentofacial deformities had a more negative
      oral health-related quality of life and a lower self-esteem compared with
      controls. No association was observed between dentofacial deformities and
      depression.

PMID- 22995692
TI  - HIV infection and stroke: current perspectives and future directions.
AB  - HIV infection can result in stroke via several mechanisms, including
      opportunistic infection, vasculopathy, cardioembolism, and coagulopathy. However,
      the occurrence of stroke and HIV infection might often be coincidental. HIV
      associated vasculopathy describes various cerebrovascular changes, including
      stenosis and aneurysm formation, vasculitis, and accelerated atherosclerosis, and
      might be caused directly or indirectly by HIV infection, although the mechanisms
      are controversial. HIV and associated infections contribute to chronic
      inflammation. Combination antiretroviral therapies (cART) are clearly beneficial,
      but can be atherogenic and could increase stroke risk. cART can prolong life,
      increasing the size of the ageing population at risk of stroke. Stroke management
      and prevention should include identification and treatment of the specific cause
      of stroke and stroke risk factors, and judicious adjustment of the cART regimen.
      Epidemiological, clinical, biological, and autopsy studies of risk, the
      pathogenesis of HIV-associated vasculopathy (particularly of arterial endothelial
      damage), the long-term effects of cART, and ideal stroke treatment in patients
      with HIV are needed, as are antiretrovirals that are without vascular risk.

PMID- 22995697
TI  - Animal injection injuries.

PMID- 22995698
TI  - Osteotomy of the radius without shortening for Kienbock disease: a 10-year follow
      up.
AB  - PURPOSE: To determine the long-term effect of distal radius osteotomy without
      modifying the radial length or inclination for Kienbock disease. METHODS: Over 9
      years, 14 patients underwent osteotomy of the distal radius without altering
      radial length or inclination. A total of 11 of these patients were available for
      follow-up after 10 or more years. We assessed pain, range of wrist motion, and
      grip strength preoperatively and postoperatively in all cases, as well as
      preoperative and postoperative posteroanterior and lateral x-rays. RESULTS: The
      osteotomy healed in all cases. All 11 patients had decreased pain and showed
      improvement in wrist motion and grip strength. Radiographically, there were no
      measurable changes in ulnar variance and there was minimal loss of carpal height.
      In some patients, the lunate showed increased sclerosis or fragmentation.
      CONCLUSIONS: An osteotomy of the distal radius without altering radial length or
      inclination was effective in decreasing pain and improving grip strength and
      wrist motion regardless of ulnar variance.

PMID- 22995699
TI  - Ulnar shortening osteotomy for ulnar impaction syndrome.

PMID- 22995700
TI  - A2 pulley insufficiency.

PMID- 22995701
TI  - Flexor tendon rehabilitation.

PMID- 22995702
TI  - Biomechanical analysis of a transverse olecranon fracture model using tension
      band wiring.
AB  - PURPOSE: To determine (1) the most distal site at which a tension band construct
      can maintain bony alignment during dynamic loading of a transverse, length-stable
      olecranon osteotomy; (2) the location of displacement during cyclical loading;
      and (3) the ultimate load to failure of the fixation. METHODS: We divided 23 non
      osteoporotic, fresh-frozen upper extremities into 4 groups. We created transverse
      osteotomies at 25% of the olecranon surface in group 1, 50% in group II, 75% in
      group III, and 100% in group IV. We used standard tension band wiring technique
      to stabilize each osteotomy. We mounted specimens on a biomechanical testing
      machine at 90 degrees  elbow flexion and subjected them to a 150-N sinusoidal
      load through the triceps tendon at 1 Hz for 500 cycles. An optical motion
      tracking system synchronized with the testing machine-measured displacement of
      the osteotomy in any plane. On completion of cycling, we loaded specimens at 1
      mm/s until 2-mm displacement occurred. We analyzed data to determine the effect
      of the location of the osteotomy on load to failure and location of displacement.
      RESULTS: Of the 23 specimens, 21 survived the cycling process. The 2 specimens
      that failed were both in group II (50%). Excluding these 2 specimens, the average
      displacement at the 3 virtual points was less than 1.05 mm in all 4 osteotomy
      groups. There were no statistical differences between groups. Load to failure was
      476, 361, 511, and 610 N for groups I to IV, respectively. Differences between
      groups were not statistically significant. CONCLUSIONS: The stability achieved
      with tension band wire fixation did not vary with the location of the osteotomy.
      CLINICAL RELEVANCE: Based on this biomechanical study, when it is properly
      executed, tension band wire fixation may be used effectively for transverse,
      length-stable fractures of the olecranon regardless of the amount of articular
      surface included on the proximal fragment.

PMID- 22995703
TI  - Promoted antitumor activities of acid-labile electrospun fibers loaded with
      hydroxycamptothecin via intratumoral implantation.
AB  - The acidosis of tumor microenvironments is one of the universal phenomena of
      solid tumors, and the increased acidity may be in fact essential intermediates in
      the progression of tumor growth and several lethal phenotypic traits of tumors,
      such as invasion and metastasis. Acid-labile polymers PBELA with incorporating
      acetal groups into biodegradable backbone of poly(d,l-lactide)-poly(ethylene
      glycol) (PELA) were utilized to load hydroxycamptothecin (HCPT) into electrospun
      fibers for intratumoral chemotherapy. Compared with that under a simulated
      physiological condition of pH 7.4, the incubation of PBELA fibers in acidic media
      resulted in larger mass loss and molecular weight reduction of fiber matrices and
      enhanced HCPT release from fibers. In vitro cytotoxicity assay of HCPT-loaded
      PBELA fibers indicated 6-fold higher inhibitory activity against HepG2 cells
      after incubation in pH 6.8 media than that of pH 7.4, while there was no
      significant difference for free HCPT and HCPT-loaded PELA fibers. The tumor
      growth, tumor cell apoptosis, and animal survival rate after intratumoral
      implantation of HCPT-loaded PBELA fibers indicated a superior in vivo antitumor
      activity and fewer side effects than other treatment. Therefore, acid-labile
      electrospun fibers may be promising implants for localized therapy of inoperable
      tumors and for prevention of post-surgical tumor recurrence.

PMID- 22995704
TI  - pH-Dependent doxorubicin release from terpolymer of starch, polymethacrylic acid
      and polysorbate 80 nanoparticles for overcoming multi-drug resistance in human
      breast cancer cells.
AB  - This work investigated the capability of a new nanoparticulate system, based on
      terpolymer of starch, polymethacrylic acid and polysorbate 80, to load and
      release doxorubicin (Dox) as a function of pH and to evaluate the anticancer
      activity of Dox-loaded nanoparticles (Dox-NPs) to overcome multidrug resistance
      (MDR) in human breast cancer cells in vitro. The Dox-NPs were characterized by
      Fourier transform infrared spectroscopy (FTIR), isothermal titration calorimetry
      (ITC), transmission electron microscopy (TEM), and dynamic light scattering
      (DLS). The cellular uptake and cytotoxicity of the Dox-loaded nanoparticles were
      investigated using fluorescence microscopy, flow cytometry, and a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. The
      nanoparticles were able to load up to 49.7+/-0.3% of Dox with a high loading
      efficiency of 99.9+/-0.1%, while maintaining good colloidal stability. The
      nanoparticles released Dox at a higher rate at acidic pH attributable to weaker
      Dox-polymer molecular interactions evidenced by ITC. The Dox-NPs were taken up by
      the cancer cells in vitro and significantly enhanced the cytotoxicity of Dox
      against human MDR1 cells with up to a 20-fold decrease in the IC50 values. The
      results suggest that the new terpolymeric nanoparticles are a promising vehicle
      for the controlled delivery of Dox for treatment of drug resistant breast cancer.

PMID- 22995705
TI  - Dual versus single Scheimpflug camera for anterior segment analysis: Precision
      and agreement.
AB  - PURPOSE: To assess the repeatability, reproducibility, and agreement of the
      Pentacam HR single-camera and Galilei G2 dual-camera Scheimpflug devices in
      anterior segment analysis. SETTING: Begitek Clinica Oftalmologica, San Sebastian,
      Spain. DESIGN: Prospective randomized observational study. METHODS: Healthy young
      individuals had 3 consecutive tests by 2 examiners. Analyzed parameters were
      anterior and posterior cornea simulated keratometry (K), K flat, K steep,
      astigmatism magnitude and axis, J(0) and J(45) vectors, asphericity, total
      corneal higher-order wavefront aberrations (root mean square [RMS], coma,
      trefoil, spherical aberration), central cornea and thinnest-point thicknesses,
      and anterior chamber depth. Repeatability and reproducibility were evaluated by
      calculating the within-subject standard deviation (S(w)), some derived
      coefficients, and the intraclass correlation coefficient. Agreement was assessed
      with the Bland-Altman method. RESULTS: The single-camera device reproducibility
      (S(w)) was simulated K, 0.04 diopter (D); J(0), 0.03 D; J(45), 0.04 D; total
      power, 0.04 D; spherical aberration, 0.02 MUm; higher-order aberrations (HOAs),
      0.02 MUm; central corneal thickness (CCT), 3.39 MUm. The dual-camera device S(w)
      was simulated K, 0.07 D; J(0), 0.13 D; J(45), 0.04 D; total power, 0.08 D;
      spherical aberration, 0.02 MUm; HOAs, 0.11 MUm; CCT, 1.36 MUm. Agreement was good
      for most parameters except total corneal power (mean difference 1.58 D +/- 0.22
      (SD) and HOA RMS (mean difference 0.48 +/- 0.19 MUm) (both P<.00). CONCLUSIONS:
      Repeatability and reproducibility were good for all parameters. The single-camera
      device was more precise for curvature, astigmatism, and corneal wavefront error
      measurements and the dual-camera device for pachymetry measurements. Agreement
      was good with some relevant exceptions. FINANCIAL DISCLOSURE: Dr. Aramberri is
      consultant to Costruzione Strumenti Oftalmici, Firenze, Italy. No other author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 22995706
TI  - From rainfall to throughfall in a maritime vineyard.
AB  - This study deals with the characteristics of throughfall produced by vine (Vitis
      vinifera L.) in one of the most common pedoclimatic conditions for grape
      production: a soil derived from marine sediments under a temperate Mediterranean
      climate, and located rather close to the seacoast. To distinguish the
      contribution of the plant from that of the atmospheric deposition, the
      throughfall was collected for more than one year under real and artificial
      (plastic) vines; for the same period, also the bulk precipitation was collected.
      The solution collected were analysed for pH, electrical conductivity, and
      concentration of cations and anions. For each event, the ionic fluxes of bulk
      precipitation and throughfall were calculated. Results indicated that the
      chemical composition of the bulk precipitation was strongly influenced by the
      proximity of the seashore and, to a lesser extent, by local anthropic activities
      and windblown material coming from distant areas. The chemical composition of the
      throughfall was affected by the same factors of bulk precipitation, but also by
      solubilisation of dry deposition trapped by the canopies, agronomic practices,
      plant, and living-on-the-leaves microorganisms. The comparison of the
      characteristics of the throughfall of the real with the artificial vines revealed
      that the vines are a source of Mg and K. During winter season, the reduction of
      Ca, NH(4) and PO(4) from bulk precipitation to throughfall was ascribed to the
      formation of biogenic minerals on the plant surface. The presence of these
      minerals was proved by X-ray diffraction on the powders collected during the
      winter season on the surface of cordons and fruiting canes. We conclude that an
      approach to the estimation of the nutritional potentiality of the soil that
      includes the contribution of the throughfall is functional to the management of
      the agro-ecosystem.

PMID- 22995707
TI  - High resolution of black carbon and organic carbon emissions in the Pearl River
      Delta region, China.
AB  - A high-resolution regional black carbon (BC) and organic carbon (OC) emission
      inventory for the year 2009 was developed for the Pearl River Delta (PRD) region,
      China, based on the collected activity data and the latest emission factors.
      PM(2.5), BC and OC emissions were estimated to be 303 kt, 39 kt and 31 kt,
      respectively. Industrial processes were major contributing sources to PM(2.5)
      emissions. BC emissions were mainly from mobile sources, accounting for 65.0%,
      while 34.1% of OC emissions were from residential combustion. The primary OC/BC
      ratios for individual cities in the PRD region were dependent on the levels of
      economic development due to differences in source characteristics, with high
      ratios in the less developed cities and low ratios in the central and southern
      developed areas. The preliminary temporal profiles were established, showing the
      highest OC emissions in winter and relatively constant BC emissions throughout
      the year. The emissions were spatially allocated into grid cells with a
      resolution of 3 km * 3 km. Large amounts of BC emissions were distributed over
      the central-southern PRD city clusters, while OC emissions exhibited a relatively
      even spatial distribution due to the significant biomass burning emissions from
      the outlying area of the PRD region. Uncertainties in carbonaceous aerosol
      emissions were usually higher than in other primary pollutants like SO(2), NO(x),
      and PM(10). One of the key uncertainty sources was the emission factor, due to
      the absence of direct measurements of BC and OC emission rates.

PMID- 22995708
TI  - Physical activity patterns and correlates among adults from a developing country:
      the Sri Lanka Diabetes and Cardiovascular Study.
AB  - OBJECTIVE: To evaluate patterns of physical activity (PA), the prevalence of
      physical inactivity and the relationships between PA and sociodemographic,
      clinical and biochemical parameters among Sri Lankan adults. DESIGN: Descriptive
      cross-sectional study. SETTING: Nationally representative population-based survey
      conducted in Sri Lanka. SUBJECTS: Data on PA and associated details were obtained
      from 5000 adults. PA was assessed using the International Physical Activity
      Questionnaire (short-form). A binary logistic regression analysis was performed
      using the dichotomous variable 'health-enhancing PA' (05'active', 15'inactive').
      RESULTS: Sample size was 4485. Mean age was 46.1 (SD 15.1) years, 39.5% were
      males. The mean weekly total MET (metabolic equivalents of task) minutes of PA
      among the study population was 4703 (SD 4369). Males (5464 (SD 5452)) had a
      significantly higher weekly total MET minutes than females (4205 (SD 3394);
      P,0.001). Rural adults (5175 (SD 4583)) were significantly more active than urban
      adults (2956 (SD 2847); P<0.001). Tamils had the highest mean weekly total MET
      minutes among ethnicities. Those with tertiary education had lowest mean weekly
      total MET minutes. In all adults 60.0% were in the 'highly active' category,
      while only 11.0% were 'inactive' (males 14.6%, females 8.7%; P<0.001). Of the
      'highly active' adults, 85.8% were residing in rural areas. Results of the binary
      logistic regression analysis indicated that female gender (OR52?1), age .70 years
      (OR53.8), urban living (OR52.5), Muslim ethnicity (OR52.7), tertiary education
      (OR53.6), obesity (OR51.8), diabetes (OR51.6), hypertension (OR51.2) and
      metabolic syndrome (OR51.3) were all associated with significantly increased odds
      of being physically 'inactive'. CONCLUSIONS: The majority of Sri Lankan adults
      were 'highly active' physically. Female gender, older age, urban living, Muslim
      ethnicity and tertiary education were all significant predictors of physical
      inactivity. Physical inactivity was associated with obesity, diabetes,
      hypertension and metabolic syndrome.

PMID- 22995709
TI  - Synergistic effect of defined artificial extracellular matrices and pulsed
      electric fields on osteogenic differentiation of human MSCs.
AB  - In vivo, bone formation is a complex, tightly regulated process, influenced by
      multiple biochemical and physical factors. To develop a vital bone tissue
      engineering construct, all of these individual components have to be considered
      and integrated to gain an in vivo-like stimulation of target cells. The purpose
      of the present studies was to investigate the synergistic role of defined
      biochemical and physical microenvironments with respect to osteogenic
      differentiation of human mesenchymal stem cells (MSCs). Biochemical
      microenvironments have been designed using artificial extracellular matrices
      (aECMs), containing collagen I (coll) and glycosaminoglycans (GAGs) like
      chondroitin sulfate (CS), or a high-sulfated hyaluronan derivative (sHya),
      formulated as coatings on three-dimensional poly(caprolactone-co-lactide) (PCL)
      scaffolds. As part of the physical microenvironment, cells were exposed to pulsed
      electric fields via transformer-like coupling (TC). Results showed that aECM
      containing sHya enhanced osteogenic differentiation represented by increases in
      ALP activity and gene-expression (RT-qPCR) of several bone-related proteins (RUNX
      2, ALP, OPN). Electric field stimulation alone did not influence cell
      proliferation, but osteogenic differentiation was enhanced if osteogenic
      supplements were provided, showing synergistic effects by the combination of sHya
      and electric fields. These results will improve the understanding of bone
      regeneration processes and support the development of effective tissue engineered
      bone constructs.

PMID- 22995710
TI  - Arginine-rich self-assembling peptides as potent antibacterial gels.
AB  - Hydrogel materials that display inherent activity against bacteria can be used to
      directly treat accessible wounds to prevent or kill existing infection. Hydrogels
      composed of self-assembling beta-hairpin peptides, having a high content of
      arginine, were found to be extremely effective at killing both gram-positive and
      gram-negative bacteria, including multi-drug resistant Pseudomonas aeruginosa. No
      added antibacterial agents are necessary to realize activity. Using self
      assembling peptides for material construction allows facile structure-activity
      relationships to be determined since changes in peptide sequence at the monomer
      level are directly transposed to the bulk material's antibacterial properties.
      SAR studies show that arginine content largely influences the hydrogel's
      antibacterial activity, and influences their bulk rheological properties. These
      studies culminated in an optimized gel, composed of the peptide PEP6R
      (VKVRVRVRV(D)PPTRVRVRVKV). PEP6R gels prepared at 1.5 wt % or higher
      concentration, demonstrate high potency against bacteria, but are cytocompatible
      toward human erythrocytes as well as mammalian mesenchymal stem cells.
      Rheological studies indicate that the gel is moderately stiff and displays shear
      thin recovery behavior, allowing its delivery via simple syringe.

PMID- 22995711
TI  - Experiences of family members of elderly patients in the emergency department: a
      qualitative study.
AB  - BACKGROUND: Elderly patients are more frequent users of emergency department
      (ED). An elderly patient entering the ED is often accompanied by a family member
      who has an important role in the patient's life. Current literature does not
      adequately address the question of the experiences of family members accompanying
      elderly patient in ED, although they could give us valuable and interesting
      knowledge and information about nursing practices. AIM: The aim of this study was
      to describe the experiences of family members of elderly patients aged over 65 in
      the ED for internal medicine. METHOD: This interview study based on the
      experiences of family members (n=9) of elderly patients being cared for in the
      ED. The interview material was analyzed using inductive content analysis.
      RESULTS: Family members of elderly patients perceived themselves as satisfied
      participants, invisible participants, or disappointed outsiders in the ED. Family
      members accompanying an elderly patient wanted to be active participants not
      being excluded, but this was possible only because of their own active attitude.
      CONCLUSIONS: Broader educational initiative for ED staff about the family
      presence and involvement in care in the ED is needed, because the family members'
      experiences showed that they were left as outsiders. Family members are well
      aware of the elderly patient's previous level of functional capacity and their
      medication, which is decisive information when planning further care and thinking
      patients coping at home.

PMID- 22995712
TI  - Molecular evolution of the neurohypophysial hormone precursors in mammals:
      Comparative genomics reveals novel mammalian oxytocin and vasopressin analogues.
AB  - Among vertebrates the neurohypophysial hormones show considerable variation.
      However, in eutherian mammals they have been considered rather conserved, with
      arginine vasopressin (AVP) and oxytocin (OT) in all species except pig and some
      relatives, where lysine vasopressin replaces AVP. The availability of genomic
      data for a wide range of mammals makes it possible to assess whether these
      peptides and their precursors may be more variable in Eutheria than previously
      suspected. A survey of these data confirms that AVP and OT occur in most
      eutherians, but with exceptions. In a New-World monkey (marmoset, Callithrix
      jacchus) and in tree shrew (Tupaia belangeri), Pro(8)OT replaces OT, confirming a
      recent report for these species. In armadillo (Dasypus novemcinctus) Leu(3)OT
      replaces OT, while in tenrec (Echinops telfairi) Thr(4)AVP replaces AVP. In these
      two species there is also evidence for additional genes/pseudogenes, encoding
      much-modified forms of AVP, but in most other eutherian species there is no
      evidence for additional neurohypophysial hormone genes. Evolutionary analysis
      shows that sequences of eutherian neurohypophysial hormone precursors are
      generally strongly conserved, particularly those regions encoding active peptide
      and neurophysin. The close association between OT and VP genes has led to
      frequent gene conversion of sequences encoding neurophysins. A monotreme,
      platypus (Ornithorhynchus anatinus) has genes for OT and AVP, organized tail-to
      tail as in eutherians, but in marsupials 3-4 genes are present for
      neurohypophysial hormones, organized tail-to-head as in lower vertebrates.

PMID- 22995713
TI  - Rapid low-cost detection of Klebsiella pneumoniae carbapenemase genes by
      internally controlled real-time PCR.
AB  - An internally controlled real-time PCR assay based on SYBR Green was developed to
      screen Klebsiella pneumoniae carbapenemases (KPCs) gene containing bacteria and
      was validated for clinical strains or surveillance specimens. When 248 clinical
      samples were tested, the sensitivity and specificity of the assay were 100% and
      99%, respectively.

PMID- 22995714
TI  - A selective medium for Rothia mucilaginosa and its distribution in oral cavities.
AB  - A selective medium for Rothia mucilaginosa (RMSM) was developed to examine the
      population of R. mucilaginosa in oral cavities. The growth recovery of R.
      mucilaginosa on RMSM was 85.1% relative to HI medium. R. mucilaginosa was
      detected at 3.4% of total bacteria from stimulated saliva of 8 subjects.

PMID- 22995715
TI  - A sandwich-culture technique for controlling antibiotic production and
      morphological development in Streptomyces coelicolor.
AB  - Antibiotic-producing streptomycetes form complex colonies consisting of
      vegetative and aerial hyphae. Here, we describe a sandwich-culture technique in
      which the mycelium grows in between two membranes, thereby preventing
      morphogenesis and antibiotic production. Both processes are restored by removal
      of the top membrane, thus providing a switch to coordinate their timing.

PMID- 22995716
TI  - Fatty acids in berry lipids of six sea buckthorn (Hippophae rhamnoides L.,
      subspecies carpatica) cultivars grown in Romania.
AB  - BACKGROUND: A systematic mapping of the phytochemical composition of different
      sea buckthorn (Hippophae rhamnoides L.) fruit subspecies is still lacking. No
      data relating to the fatty acid composition of main lipid fractions from the
      berries of ssp. carpatica (Romania) have been previously reported. RESULTS: The
      fatty acid composition of the total lipids (oils) and the major lipid fractions
      (PL, polar lipids; FFA, free fatty acids; TAG, triacylglycerols and SE, sterol
      esters) of the oils extracted from different parts of six sea buckthorn berry
      subspecies (ssp. carpatica) cultivated in Romania were investigated using the gas
      chromatography-mass spectrometry (GC-MS). The dominating fatty acids in pulp/peel
      and whole berry oils were palmitic (23-40%), oleic (20-53%) and palmitoleic (11
      27%). In contrast to the pulp oils, seed oils had higher amount of
      polyunsaturated fatty acids (PUFAs) (65-72%). The fatty acid compositions of TAGs
      were very close to the compositions of corresponding seed and pulp oils. The
      major fatty acids in PLs of berry pulp/peel oils were oleic (20-40%), palmitic
      (17-27%), palmitoleic (10-22%) and linoleic (10%-20%) acids, whereas in seeds
      PLs, PUFAs prevailed. Comparing with the other lipid fractions the SEs had the
      highest contents of saturated fatty acids (SFAs). The fatty acid profiles of the
      FFA fractions were relatively similar to those of TAGs. CONCLUSIONS: All parts of
      the analyzed sea buckthorn berry cultivars (ssp. carpatica) exhibited higher oil
      content then the other European or Asiatic sea buckthorn subspecies. Moreover,
      the pulp/peel oils of ssp. carpatica were found to contain high levels of oleic
      acid and slightly lower amounts of linoleic and alpha-linolenic acids. The
      studied cultivars of sea buckthorn from Romania have proven to be potential
      sources of valuable oils.

PMID- 22995718
TI  - Wnt/beta-catenin signaling in embryonic stem cell converted tumor cells.
AB  - BACKGROUND: Embryonic stem cells (ESCs) are pluripotent stem cells and can form
      tumors containing cells from all three germ layers. Similarities between
      pluripotent stem cells and malignant tumor cells have been identified. The
      purpose of this study was to obtain ESCs-converted tumor cell lines and to
      investigate the mechanism of malignancy in pluripotent stem cells. METHODS: Mouse
      ESCs were subcutaneously injected into nude mice to obtain tumors from which a
      tumor-like cell line (ECCs1) was established by culturing the cells in chemical
      defined N2B27 medium supplied with two small molecular inhibitors CHIR99021 and
      PD0325901 (2i). The ECCs1 were then subcutaneously injected into nude mice again
      to obtain tumors from which another tumor-like cells line (ECCs2) was established
      in the same 2i medium. The malignant degree of ESCs, ECCs1 and ECCs2 was compared
      and the underlying mechanism involved in the malignancy development of ESCs was
      examined. RESULTS: The three ESCs, ECCs1 and ECCs2 cell lines were cultured in
      the same 2i condition and showed some likeness such as Oct4-expression and long
      term expansion ability. However, the morphology and the tumor-formation ability
      of the cell lines were different. We identified that ECCs1 and ECCs2 gradually
      acquired malignancy. Moreover, Wnt signaling-related genes such as CD133 and beta
      catenin expression were up-regulated and Frizzled related protein (FRP) was down
      regulated during the tumor development of ESCs. CONCLUSIONS: The two tumor-like
      cell lines ECCs1 and ECCs2 stand for early malignant development stage of ESCs
      and the ECCs2 was more malignant than the ECCs1. Moreover, we identified that
      Wnt/beta-catenin signaling played an important role in the malignancy process of
      ESCs.

PMID- 22995719
TI  - Canine leishmaniosis in the Old and New Worlds: unveiled similarities and
      differences.
AB  - Canine leishmaniosis is a potentially life-threatening disease which is spreading
      geographically in the Old and New Worlds, where different diagnostic procedures,
      treatments, and control strategies are currently in place. This Opinion article
      outlines the similarities and differences between canine leishmaniosis in the Old
      and New Worlds, with emphasis on South America and Europe. Finally, it calls the
      attention of veterinary and public health authorities to standardize and improve
      practices for diagnosing, treating, and preventing the disease.

PMID- 22995720
TI  - Determination of protein subcellular localization in apicomplexan parasites.
AB  - Parasites from the phylum Apicomplexa include causative agents of serious
      diseases including malaria (Plasmodium spp.) and toxoplasmosis (Toxoplasma
      gondii). Apicomplexan parasites infect thousands of types of animal cells and
      send their proteins to an array of compartments within their own cell, as well as
      exporting proteins into and beyond their host cell. Ascertaining destinations to
      which individual proteins are delivered allows researchers to better understand
      parasite biology and to identify potential targets for therapeutic interventions.
      Our toolkit for establishing subcellular locations of apicomplexan proteins is
      becoming more extensive and specialized, and here we review developments in this
      technology.

PMID- 22995721
TI  - Transplantation of initially rejected donor lungs after ex vivo lung perfusion.
AB  - OBJECTIVE: Ex vivo lung perfusion has the potential to increase the number of
      patients treated with lung transplantation. Our initial clinical experience with
      ex vivo lung perfusion is reviewed as well as early clinical outcome in patients
      transplanted with reconditioned lungs. METHODS: Six pairs of donor lungs deemed
      unsuitable for transplantation underwent ex vivo lung perfusion with Steen
      solution mixed with red blood cells to a hematocrit of 10% to 15%. After
      reconditioning, lung function was evaluated and acceptable lungs were
      transplanted. Technical experience with ex vivo lung perfusion as well as
      clinical outcome for patients transplanted with ex vivo lung perfusion-treated
      lungs were evaluated. RESULTS: Donor lungs initially rejected either as a result
      of an inferior partial pressure of arterial oxygen/ fraction of inspired oxygen
      (n = 5; mean, 20.5 kPa; range, 9.1-29.9 kPa) or infiltrate on chest radiograph (n
      = 1) improved their oxygenation capacity to a mean partial pressure of arterial
      oxygen/fraction of inspired oxygen of 57 +/- 10 kPa during the ex vivo lung
      perfusion (mean improvement, 33.6 kPa; range, 21-51 kPa; P < .01). During
      evaluation, hemodynamic (flow, vascular resistance, pressure) and respiratory
      (peak airway pressure, compliance) parameters were stable. Two single lungs were
      not used for lung transplantation because of subpleural hematoma or edema. Six
      recipients from the regular waiting list underwent single (n = 2) or double (n =
      4) lung transplantation. One patient had primary graft dysfunction grade 2 at 72
      hours. Median time to extubation was 7 hours. All patients survived 30 days and
      were discharged in good condition from the hospital. CONCLUSIONS: The use of ex
      vivo lung perfusion seems safe and indicates that some lungs otherwise refused
      for lung transplantation can be recovered and transplanted with acceptable short
      term results.

PMID- 22995723
TI  - Atorvastatin increases oxidative stress and modulates angiogenesis in Ossabaw
      swine with the metabolic syndrome.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the effect of
      atorvastatin on oxidative stress and angiogenesis in ischemic myocardium in a
      clinically relevant porcine model of the metabolic syndrome. METHODS: Sixteen
      Ossabaw pigs were fed either a high-fat diet alone or a high-fat diet
      supplemented with atorvastatin (1.5 mg/kg daily) for 14 weeks. Chronic myocardial
      ischemia was induced by ameroid constrictor placement around the circumflex
      artery. After 6 months of the diet, myocardial perfusion was measured at rest and
      with demand pacing. The heart was harvested for analysis of perfusion,
      microvessel relaxation, protein expression, and oxidative stress. RESULTS: Both
      groups had similar endothelium-dependent microvessel relaxation to adenosine
      diphosphate and endothelium-independent relaxation to sodium nitroprusside.
      Myocardial perfusion in the ischemic territory was also not significantly
      different either at rest or with demand pacing. Atorvastatin treatment increased
      total myocardial protein oxidation and serum lipid peroxidation. However, the
      expression of markers of oxidative stress, including NOX2, RAC1, myeloperoxidase,
      and superoxide dismutase 1, 2, and 3, were not statistically different. The
      expression of proangiogenic proteins endothelial nitric oxide synthase,
      phosphorylated endothelial nitric oxide synthase (Ser 1177), phosphorylated
      adenosine monophosphate kinase (Thr 172), phosphorylated extracellular signal
      regulated kinase (T202, Y204), and vascular endothelial growth factor were all
      upregulated in the atorvastatin group. CONCLUSIONS: Atorvastatin increased the
      capillary and arteriolar density and upregulated the proangiogenic proteins
      endothelial nitric oxide synthase and phosphorylated endothelial nitric oxide
      synthase, phosphorylated adenosine monophosphate kinase, phosphorylated
      extracellular signal-regulated kinase, and vascular endothelial growth factor in
      a swine model of the metabolic syndrome. However, it failed to increase
      myocardial perfusion. Atorvastatin treatment was associated with increased
      myocardial and serum oxidative stress, which might contribute to the lack of
      collateral-dependent perfusion in the setting of angiogenesis.

PMID- 22995725
TI  - Aortic root conservative repair of acute type A aortic dissection involving the
      aortic root: fate of the aortic root and aortic valve function.
AB  - OBJECTIVES: Despite many studies about aortic valve function and aortic root
      geometry after conservative aortic root repair of acute type A aortic dissection,
      the results are not always consistent or conclusive. This study aims to evaluate
      aortic root diameter and aortic valve function after surgery for acute type A
      aortic dissection involving the aortic root. METHODS: A retrospective review was
      performed of 196 consecutive patients (age, 56.9 +/- 11.4 years; 96 men) who
      underwent conservative aortic root repair including sinotubular junction
      resuspension for the management of acute type A aortic dissection involving the
      aortic root. RESULTS: The 30-day mortality rate was 5.1% (n = 10). During a
      median follow-up period of 45.3 +/- 36.4 months, there were 28 deaths and 11
      cases of aortic reoperation (proximal reoperation in 1 and distal reoperation in
      10). Of the 6-month survivors (n = 177, 90.3%), echocardiography and computed
      tomography were performed in the late period (>6 months) on 115 (65.0%) and 138
      (78.0%), respectively. Significant aortic regurgitation (greater than grade 2+)
      or root dilatation (>45 mm) was observed in 5 and 19 patients, respectively.
      Freedom from aortic regurgitation (greater than grade 2+) or root dilatation (>45
      mm) at 5 years was 84.6% +/- 3.9%. On the Cox regression analysis, the maximal
      aortic root diameter at initial presentation was the only significant predictor
      of aortic regurgitation and aortic root dilatation (hazard ratio, 1.10; 95%
      confidence interval, 1.02-1.19; P = .014). CONCLUSIONS: Conservative aortic root
      repair of acute type A aortic dissection demonstrates acceptable long-term
      clinical outcomes. However, more aggressive approaches should be considered for
      patients who have aortic root dilatation because of the risk of developing a root
      aneurysm after surgery.

PMID- 22995722
TI  - Importance of atrial surface area and refractory period in sustaining atrial
      fibrillation: testing the critical mass hypothesis.
AB  - OBJECTIVE: The critical mass hypothesis for atrial fibrillation (AF) was proposed
      in 1914; however, there have been few studies defining the relationship between
      atrial surface area and AF. This study evaluated the effect of tissue area and
      effective refractory period (ERP) on the probability of sustaining AF in an in
      vivo model. METHODS: Domestic pigs (n = 9) underwent median sternotomy.
      Epicardial activation maps were constructed from bipolar electrograms recorded
      from form-fitting electrode templates placed on the atria. Baseline ERPs were
      determined. ERP was lowered with a continuous infusion of acetylcholine (0.005
      0.04 mg/Kg/min) until AF could be sustained after burst pacing. The atria were
      sequentially partitioned using bipolar radiofrequency ablation. ERPs were lowered
      using acetylcholine until AF could be sustained in each subdivision of atrial
      tissue. Each subdivision was further divided until AF was no longer inducible. At
      study completion, the heart was excised and the surface area of each section was
      measured. RESULTS: Over a range of ERPs from 75 to 250 ms, the probability of AF
      was correlated with increasing tissue area (range, 19.5-105 cm(2)) and decreasing
      ERP. Logistic regression analysis identified shorter ERP (P < .001) and larger
      area (P = .006) as factors predictive of an increased probability of sustained AF
      (area under the curve of the receiver-operator characteristic = 0.878).
      CONCLUSIONS: The probability of sustained AF was significantly associated with
      increasing tissue area and decreasing ERP. These data may lead to a greater
      understanding of the mechanism of AF and help to design better interventional
      procedures.

PMID- 22995726
TI  - Transfusion outcomes in patients undergoing coronary artery bypass grafting
      treated with prasugrel or clopidogrel: TRITON-TIMI 38 retrospective data
      analysis.
AB  - OBJECTIVE: Coronary artery bypass grafting-related bleeding and associated
      transfusion is a concern with dual antiplatelet therapy in patients with acute
      coronary syndromes. The objective of the present study was to characterize a
      potential risk-adjusted difference in transfusion requirements between prasugrel
      and clopidogrel cohorts. METHODS: The data from 422 patients undergoing isolated
      coronary artery bypass grafting from the TRial to assess Improvement in
      Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel
      Thrombolysis In Myocardial Infarction 38 were analyzed retrospectively. RESULTS:
      We found no difference in baseline transfusion risk scores between cohorts. As
      predicted, the number of units of red blood cells transfused perioperatively
      correlated with the transfusion risk score (P < .0001). Overall, the 12-hour
      chest tube drainage volumes and platelet transfusion rates in the prasugrel
      cohort were significantly greater. However, no statistically significant
      differences were found in the number of red blood cell transfusions, total
      hemostatic components transfused, or total blood donor exposure. A significantly
      greater number of platelet units were transfused postoperatively in the prasugrel
      patients who underwent surgery within 5 days or less after withdrawal of drug. In
      an analysis adjusted for the predicted risk of mortality, total donor exposure
      was not associated with increased mortality. CONCLUSIONS: The use of prasugrel
      compared with clopidogrel was associated with greater 12-hour chest tube drainage
      volumes and platelet transfusion rates but without any significant differences in
      red blood cell transfusions, total hemostatic components transfused, or total
      blood donor exposure.

PMID- 22995727
TI  - The effect of center volume on the incidence of postoperative complications and
      their impact on survival after lung transplantation.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of center volume on
      the incidence of postoperative complications and their impact on survival after
      lung transplantation (LTx). METHODS: United Network for Organ Sharing data were
      used to identify adult patients undergoing LTx between 1999 and 2009. Center
      volume was modeled as both a continuous and a categorical variable. Postoperative
      complications included infection, rejection, stroke, reoperation, and renal
      failure requiring dialysis. Multivariable Cox regression and Kaplan-Meier
      analyses were conducted after stratification on the basis of center volume and
      type of complication. RESULTS: A total of 12,565 LTx recipients were included in
      the study. Overall rates of postoperative complications were 5.4% for renal
      failure requiring dialysis, 1.9% for stroke, 19.9% for reoperation, 42.8% for
      infection, and 10.0% for rejection. High volume centers did not have
      significantly reduced rates of postoperative complications. Risk-adjusted
      multivariable Cox analysis demonstrated that in patients with a complication, low
      volume center was a significant risk factor for increased 90-day, 1-year, and 5
      year mortality. Kaplan-Meier analyses similarly demonstrated reduced
      posttransplant survival in lower volume centers, a finding that persisted after
      stratification based on individual complication type except for stroke.
      CONCLUSIONS: Although high volume centers do not have significantly lower
      incidences of individual postoperative complications after LTx, they are best
      able to minimize the adverse effects of these complications on short- and long
      term survival. These data suggest that identifying and implementing the
      institutional practices that lead to better management of postoperative
      complications after LTx in high volume centers may be prudent to improving
      outcomes in lower volume hospitals.

PMID- 22995728
TI  - Complexity of coronary artery disease affects outcome of patients undergoing
      coronary artery bypass grafting with impaired left ventricular function.
AB  - OBJECTIVE: To determine whether the SYNTAX score can predict the outcomes of
      patients with left ventricular dysfunction undergoing coronary artery bypass
      grafting. METHODS: We studied a consecutive series of 191 patients (mean age, 67
      +/- 10 years) with a left ventricular ejection fraction of 40% or less who were
      undergoing isolated coronary artery bypass grafting. All patients were stratified
      according to their SYNTAX score, indicating coronary artery disease complexity:
      low, 0 to 22; intermediate, 23 to 32; and high, 33 or more. The primary outcome
      was all-cause mortality. Secondary outcomes included the late occurrence of major
      adverse cardiac and cerebrovascular events, left ventricular function, and New
      York Heart Association functional class. RESULTS: The mean SYNTAX score was 32 +/
      13, and the mean preoperative left ventricular ejection fraction was 35% +/- 6%.
      At a median follow-up of 43 months, the primary outcome had occurred in 46 of 191
      patients (24%). Kaplan-Meier analysis showed a survival of 81% +/- 15% for low,
      77% +/- 7% for intermediate, and 53% +/- 7% for high coronary artery disease
      complexity (chi(2), 29.4; P = .001). The rate of major adverse cardiac and
      cerebrovascular events was significantly greater in patients with a SYNTAX score
      of 33 or more (P = .002). Greater degrees of left ventricular ejection fraction
      improvement were found in patients with a SYNTAX score of 32 or less (+15% +/-
      10% vs +4% +/- 11%; P = .17) and translated into a better New York Heart
      Association functional class among patients with a lower SYNTAX score (P = .01).
      Receiver operating characteristic curve analysis showed the SYNTAX score (area
      under the curve, 0.70; 95% confidence interval, 0.63-0.77) to have the best
      predictive power for late mortality with respect to the preoperative left
      ventricular ejection fraction (area under the curve, 0.59; difference, P = .04)
      and incomplete revascularization (area under the curve, 0.55; difference, P =
      .02). CONCLUSIONS: The results of the present study have shown a direct
      relationship between coronary artery disease complexity and late outcomes of
      patients with left ventricular dysfunction who are undergoing coronary artery
      bypass grafting. Additional studies are needed to confirm these findings.

PMID- 22995729
TI  - The pantheon of the fallen: why are there so many forms of cell death?
AB  - Cells die by various mechanisms, only some of which have been elucidated in
      detail. Numerous 'active' forms of cell death exist in which the cell
      participates in its own death, including apoptosis, programmed necrosis, mitotic
      catastrophe, and the recently described ferroptosis. Here, we attempt to explain
      why there are so many different forms of cell death, and propose a distinction
      between active death that constitutes 'suicide' versus 'sabotage'.

PMID- 22995730
TI  - The nuclear factor kappa B signaling pathway: integrating metabolism with
      inflammation.
AB  - Nuclear factor kappa B (NF-kappaB) transcription factors are evolutionarily
      conserved, coordinating regulators of immune and inflammatory responses. They
      also play a pivotal role in oncogenesis and metabolic disorders. Several studies
      during the past two decades have highlighted the key role of the IKK/NF-kappaB
      pathway in the induction and maintenance of the state of inflammation that
      underlies metabolic diseases such as obesity and type 2 diabetes. Recent reports,
      however, reveal an even more intimate connection between NF-kappaB and
      metabolism. These studies demonstrate that NF-kappaB regulates energy homeostasis
      via direct engagement of the cellular networks governing glycolysis and
      respiration, with profound implications beyond metabolic diseases, including
      cancer, ageing and anticancer therapy. In this review, we discuss these emerging
      bioenergetic functions of NF-kappaB and their significance to oncogenesis.

PMID- 22995732
TI  - Prevalence and predictors of impaired fasting glucose among Nigerian patients
      with hepatitis B virus infection.
AB  - AIM: Previous studies on the relationship between hepatitis B virus (HBV)
      infection and type 2 diabetes mellitus (DM) are conflicting. We aimed to
      elucidate the relationship by investigating the prevalence and predictors of
      impaired fasting glucose (IFG) in HBV-infected patients. METHODS: A total of 204
      consecutive patients with hepatitis B surface antigen (HBsAg) seropositivity for
      >= 6 months were recruited in a cross-sectional study. Patients with DM were
      excluded. Information regarding age, gender, ethnicity, residence, family history
      of DM, alcohol use, and cigarette smoking were obtained using a structured
      questionnaire. Fasting plasma glucose, lipid profile, liver enzymes and hepatitis
      Be antigen (HBeAg) were tested. RESULTS: The participants had a mean age of 33.6
      +/- 8.4 years and included 123 (60.3%) females, 40 (19.6%) with HBeAg
      seropositivity, and 29 (14.2%) with family history of DM. The prevalence of IFG
      was 52 (25.5%). On multivariate analysis, the independent predictors of IFG were
      family history of DM (OR = 8.23, 95% CI = 2.78-24.31), male gender (OR = 2.83,
      95% CI = 1.17-6.64), HBeAg seropositivity (OR = 4.97, 95% CI = 1.87-13.18) and
      elevated GGT (OR = 7.27, 95% C.I = 2.88-18.35). CONCLUSION: The prevalence of IFG
      among HBV-infected patients is high. Targeted screening and follow-up of HBV
      infected patients for abnormalities of glucose metabolism is recommended.

PMID- 22995733
TI  - [Innate and adaptative immunity of the female genital tract].
AB  - Most of molecules and cells involved in both types, innate and adaptive immunity
      are present within the feminine genital tract. This article attempts to list some
      of the various actors involved in these immunities, essentially at the vaginal
      level and to illustrate their implications in the most frequent pathologies.
      Among these molecules: defensins, collectins lysozyme, lactoferrin, calprotectin,
      SLP1, HSP and many others as well as Toll receptors and immunoglobulins (IgG and
      IgA) play a major role. Epithelial cells, antigen presenting cells, lymphocytes
      T, B, NK also contribute efficiently to the defenses in a coordinated way
      partially under the influence of sex hormones. The therapeutic perspectives, of
      which vaccines are briefly mentioned.

PMID- 22995734
TI  - Associations between vitamin D deficiency and risk of aggressive breast cancer in
      African-American women.
AB  - Although breast cancer incidence in the US is highest for women of European
      ancestry (EA), women of African ancestry (AA) have higher incidence of cancer
      diagnosed before age 40 and tumors with more aggressive features (high grade and
      negative for estrogen receptor (ER), progesterone receptor (PR) and human
      epidermal growth factor receptor (HER2)), which precludes targeted therapies and
      leads to poorer outcomes. It is unclear what underlies these disparities. It has
      been hypothesized that dark skin with high melanin content is the ancestral skin
      color of origin, with adaptation to northern environs resulting in lighter skin.
      Although intense sunlight in sub-Saharan Africa may compensate for low sun
      absorption through skin, an urban or western lifestyle may result in less
      synthesis of vitamin D with higher skin pigmentation. Laboratory and preclinical
      data indicate that vitamin D is involved in preventing breast carcinogenesis and
      progression. Vitamin D receptor (VDR) knock-out mice are more likely to develop
      tumors that are ER-negative, and we have shown that serum levels of 25OHD are
      lowest among EA women with triple-negative tumors (negative for ER, PR and HER2);
      and among non-cancer patients, vitamin D levels are lower in AAs than in EAs.
      Thus, it is plausible to hypothesize that low vitamin D levels could be
      associated with the higher prevalence of more aggressive tumors among AA women.
      In this paper, we review the current literature on vitamin D and aggressive
      breast cancer subtypes, discuss vitamin D in AA women from a perspective of
      evolution and adaption, and examine the potential role of vitamin D in cancer
      racial disparities. We present our recently published data showing two single
      nucleotide polymorphisms in vitamin D catabolic enzyme CYP24A1 associated with
      higher risk of estrogen ER-negative risk in AA than in EA women. The relationship
      of vitamin D with breast cancer risk may be subtype-specific, with emerging
      evidence of stronger effects of vitamin D for more aggressive breast cancer,
      particularly in women of African ancestry.

PMID- 22995735
TI  - Maternal to offspring resource allocation in plants and mammals.
AB  - Appropriate allocation of resources to the offspring is critical for successful
      reproduction, particularly in species that reproduce on more than one occasion.
      The offspring must be provisioned adequately to ensure its vigour, whereas the
      parent must not become so depleted such that its survival is endangered. In both
      flowering plants and mammals specialised structures have evolved to support the
      offspring during its development. In this review we consider common themes that
      may indicate conservation of nutrient transfer function and regulation by genomic
      imprinting across the two kingdoms.

PMID- 22995736
TI  - Micronutrient intake and status in Central and Eastern Europe compared with other
      European countries, results from the EURRECA network.
AB  - OBJECTIVE: To compare micronutrient intakes and status in Central and Eastern
      Europe (CEE) with those in other European countries and with reference values.
      DESIGN: Review of the micronutrient intake/status data from open access and grey
      literature sources from CEE. SETTING: Micronutrients studied were folate, iodine,
      Fe, vitamin B12 and Zn (for intake and status) and Ca, Cu, Se, vitamin C and
      vitamin D (for intake). Intake data were based on validated dietary assessment
      methods; mean intakes were compared with average nutrient requirements set by the
      Nordic countries or the US Institute of Medicine. Nutritional status was assessed
      using the status biomarkers and cut-off levels recommended primarily by the WHO.
      SUBJECTS: For all population groups in CEE, the mean intake and mean/median
      status levels were compared between countries and regions: CEE, Scandinavia,
      Western Europe and Mediterranean. RESULTS: Mean micronutrient intakes of adults
      in the CEE region were in the same range as those from other European regions,
      with exception of Ca (lower in CEE). CEE children and adolescents had poorer
      iodine status, and intakes of Ca, folate and vitamin D were below the reference
      values. CONCLUSIONS: CEE countries are lacking comparable studies on
      micronutrient intake/status across all age ranges, especially in children.
      Available evidence showed no differences in micronutrient intake/status in CEE
      populations in comparison with other European regions, except for Ca intake in
      adults and iodine and Fe status in children. The identified knowledge gaps urge
      further research on micronutrient intake/status of CEE populations to make a
      basis for evidence-based nutrition policy.

PMID- 22995737
TI  - Implementing practice guidelines for anxiety disorders in secondary mental health
      care: a case study.
AB  - BACKGROUND: Recent years have seen the large-scale development of clinical
      practice guidelines for mental disorders in several countries. In the
      Netherlands, more than ten multidisciplinary guidelines for mental health care
      have been developed since 2003. The first dealt with the treatment of anxiety
      disorders. An important question was whether it is feasible to implement these
      guidelines because implementing practice guidelines is often difficult. Although
      several implementation interventions have proven effective, there seems to be no
      ready-made strategy that works in all circumstances. CASE DESCRIPTION: The Dutch
      multidisciplinary guidelines for anxiety disorders were implemented in a
      community mental health care centre, located in the east of the Netherlands. The
      centre provides secondary outpatient care. The unit within the centre that
      specializes in the treatment of anxiety disorders has 16 team members with
      diverse professional backgrounds. Important steps in the process of implementing
      the guidelines were analysing the care provided before start of the
      implementation to determine the goals for improvement, and analysing the context
      and target group for implementation. Based on these analyses, a tailor-made
      multifaceted implementation strategy was developed that combined the
      reorganization of the care process, the development of instruction materials, the
      organization of educational meetings and the use of continuous quality circles to
      improve adherence to guidelines. DISCUSSION AND EVALUATION: Significant
      improvements in adherence rates were made in the aspect of care that was targeted
      for change. An increase was found in the number of patients being provided with
      recommended forms of psychotherapeutic treatment, ranging from 43% to 54% (p <
      0.01). The delivery of adequate pharmacological treatment was not explicitly
      targeted for change remained constant. CONCLUSION: The case study presented here
      shows that the implementation of practice guidelines for anxiety disorders in
      mental health care is feasible. Based on the results of our study, the
      implementation model used offers a useful approach to guideline implementation.
      By describing the exact steps that were followed in detail and providing some of
      the tools that were used in the study, we hope the replication of this
      implementation methodology is made more practical for others in the future.

PMID- 22995738
TI  - Agenda driven publications.

PMID- 22995739
TI  - How much should we pursue an elevated prostate specific antigen?

PMID- 22995740
TI  - Use of hydrophilic ionic liquids in a two-phase system to improve Mung bean
      epoxide hydrolases-mediated asymmetric hydrolysis of styrene oxide.
AB  - A comparative study was made of Mung bean epoxide hydrolases-catalyzed asymmetric
      hydrolysis of styrene oxide to (R)-1-phenyl-1,2-ethanediol in an n-hexane/buffer
      biphasic system containing various hydrophilic ionic liquids (ILs). Compared to
      the n-hexane/buffer biphasic system alone, addition of a small amount of
      hydrophilic ILs reduced the amount of non-enzymatic hydrolysis, and improved the
      reaction rate by up to 22%. The ILs with cation containing an alkanol group,
      namely [C(2)OHMIM][BF(4)] and [C(2)OHMIM][TfO], and the choline amino acid ILs
      [Ch][Arg] and [Ch][Pro] were found to be the most suitable co-solvents for the
      reaction, owing to their good biocompatibility with the enzyme, which led to high
      initial rates (0.99-1.25 MUmol/min) and high product e.e.s (95%). When substrate
      concentration was around 30 mM, where optimal performance was observed with the
      IL-containing systems, the product e.e. was improved from 90% without ILs to
      >=95% in the presence of ILs.

PMID- 22995741
TI  - Characterization of recombinant human C1 inhibitor secreted in milk of transgenic
      rabbits.
AB  - C1 inhibitor (C1INH) is a single-chain glycoprotein that inhibits activation of
      the contact system of coagulation and the complement system. C1INH isolated from
      human blood plasma (pd-hC1INH) is used for the management of hereditary
      angioedema (HAE), a disease caused by heterozygous deficiency of C1INH, and is a
      promise for treatment of ischemia-reperfusion injuries like acute myocardial or
      cerebral infarction. To obtain large quantities of C1INH, recombinant human C1INH
      (rhC1INH) was expressed in the milk of transgenic rabbits (12 g/l) harboring
      genomic human C1INH sequences fused to 5' bovine alphaS(1) casein promoter
      sequences. Recombinant hC1INH was isolated from milk to a specific activity of
      6.1 U/mg and a purity of 99%; by size-exclusion chromatography the 1% impurities
      consisted of multimers and N-terminal cleaved C1INH species. Mass spectrometric
      analysis of purified rhC1INH revealed a relative molecular mass (M(r)) of 67,200.
      Differences in M(r) on SDS PAGE and mass spectrometric analysis between rhC1INH
      and pd-hC1INH are explained by differential glycosylation (calculated
      carbohydrate contents of 21% and 28%, respectively), since protein sequencing
      analysis of rhC1INH revealed intact N- and C-termini. Host-related impurity
      analysis by ELISA revealed trace amounts of rabbit protein (approximately 10 ppm)
      in purified batches, but not endogenous rabbit C1INH. The kinetics of inhibition
      of the target proteases C1s, Factor XIIa, kallikrein and Factor XIa by rhC1INH
      and pd-hC1INH, indicated comparable inhibitory potency and specificity. Recently,
      rhC1INH (Ruconest((r))) has been approved by the European Medicines Agency for
      the treatment of acute attacks of HAE.

PMID- 22995742
TI  - Effect of pH on biosynthesis of lovastatin and other secondary metabolites by
      Aspergillus terreus ATCC 20542.
AB  - The effect of the initial pH value of the cultivation medium on lovastatin
      (mevinolinic acid) biosynthesis by Aspergillus terreus ATCC20542 was studied. It
      was found that if the pH value of the broth is acidic, the direct chromatographic
      assay of mevinolinic acid leads to the underestimated values. Thus, the
      equilibrium curve was determined for the transformation of beta-hydroxy acid form
      of lovastatin (mevinolinic acid) into lovastatin lactone. The calculation of the
      equilibrium constant shows that when the pH value of the solution is 4.98,
      concentrations of both forms of lovastatin are equal to each other. This finding
      was next used to study mevinolinic acid formation at the various initial pH
      values of the medium. It occurs that even at pH lower than 5.5 mevinolinic acid
      is still, although inefficiently, produced and its presence remains unnoticed,
      unless the samples of the broth are alkalised prior to the assay. Mevinolinic
      acid is efficiently produced at the initial pH value of the medium equal to 7.5
      and 8.5 and it correlates with the rapid utilisation of lactose by A. terreus.
      Additionally, other secondary metabolites were sought at the various initial pH
      values of the medium with the use of mass spectrometry. (+)-Geodin is only formed
      at pH 6.5, while monacolin L is found at the highest amount at pH 7.5.

PMID- 22995743
TI  - A distinctive Western blot pattern to recognize Trichinella infections in humans
      and pigs.
AB  - Trichinellosis is a zoonotic disease caused by parasites of the genus
      Trichinella, which have a cosmopolitan distribution. For diagnostic purposes, a
      confirmatory test for ELISA-positive human and pig sera such as Western blotting
      is required, due to the high number of ELISA false positive sera. The objective
      of this study was to identify the Trichinella-specific antigens most frequently
      recognized by sera from Trichinella-infected humans and pigs, so as to define a
      distinctive pattern of Trichinella infection in sera from infected hosts using
      Western blots which allow false positive sera to be distinguished from true
      positive sera. Using excretory/secretory antigens, 450 human sera were tested by
      Western blotting: 150 from persons with a confirmed diagnosis of trichinellosis
      and 300 from persons who did not have trichinellosis but who tested positive by
      ELISA (i.e., false positives). We also tested 210 pig sera: (i) 30 from pigs
      experimentally infected with Trichinella spiralis; (ii) 90 from naturally T.
      spiralis-infected pigs; and (iii) 90 from pigs not infected with Trichinella, as
      shown after artificial digestion of the diaphragm pillars, yet which tested
      positive by ELISA (i.e., false positives). All true positive sera (i.e., sera
      from persons with confirmed trichinellosis as well as sera from naturally and
      experimentally infected pigs), reacted with a three-band pattern ranging in size
      from 48-72kDa. A distinctive pattern for recognizing Trichinella spp. infections
      in humans and pigs by Western blots is defined; it shows a sensitivity of 100%
      and it allows sera from Trichinella-infected humans and pigs to be distinguished
      from sera from persons and pigs that were not infected with Trichinella spp.
      (100% specificity).

PMID- 22995744
TI  - Cardiovascular magnetic resonance physics for clinicians: Part II.
AB  - This is the second of two reviews that is intended to cover the essential aspects
      of cardiovascular magnetic resonance (CMR) physics in a way that is
      understandable and relevant to clinicians using CMR in their daily practice.
      Starting with the basic pulse sequences and contrast mechanisms described in part
      I, it briefly discusses further approaches to accelerate image acquisition. It
      then continues by showing in detail how the contrast behaviour of black blood
      fast spin echo and bright blood cine gradient echo techniques can be modified by
      adding rf preparation pulses to derive a number of more specialised pulse
      sequences. The simplest examples described include T2-weighted oedema imaging,
      fat suppression and myocardial tagging cine pulse sequences. Two further
      important derivatives of the gradient echo pulse sequence, obtained by adding
      preparation pulses, are used in combination with the administration of a
      gadolinium-based contrast agent for myocardial perfusion imaging and the
      assessment of myocardial tissue viability using a late gadolinium enhancement
      (LGE) technique. These two imaging techniques are discussed in more detail,
      outlining the basic principles of each pulse sequence, the practical steps
      required to achieve the best results in a clinical setting and, in the case of
      perfusion, explaining some of the factors that influence current approaches to
      perfusion image analysis. The key principles of contrast-enhanced magnetic
      resonance angiography (CE-MRA) are also explained in detail, especially focusing
      on timing of the acquisition following contrast agent bolus administration, and
      current approaches to achieving time resolved MRA. Alternative MRA techniques
      that do not require the use of an endogenous contrast agent are summarised, and
      the specialised pulse sequence used to image the coronary arteries, using
      respiratory navigator gating, is described in detail. The article concludes by
      explaining the principle behind phase contrast imaging techniques which create
      images that represent the phase of the MR signal rather than the magnitude. It is
      shown how this principle can be used to generate velocity maps by designing
      gradient waveforms that give rise to a relative phase change that is proportional
      to velocity. Choice of velocity encoding range and key pitfalls in the use of
      this technique are discussed.

PMID- 22995745
TI  - Genetic association of adipokine and UCP2 polymorphism with recurrent miscarriage
      among non-obese women.
AB  - The adipokines produced from adipose tissues influence energy homeostasis,
      resulting in alterations of the adipokine concentrations. This process may be
      associated with fertility impairment, resulting in recurrent miscarriage. The
      present study investigated whether there was any association between the UCP2 45
      bp indel polymorphism and the adipokine gene polymorphisms, namely leptin 2549
      (C/A), adeponectin 276 (G/T) and 45 (T/G) and resistin 420 (C/G) in 200 non-obese
      recurrent miscarriage patients and 300 ethnically matched negative controls.
      These markers were studied using gene-specific PCR single specific primer and
      restriction fragment length polymorphism. For leptin 2549 and adeponectin 276,
      the A allele and G allele showed 3.42-fold (P=0.0001) and 1.36-fold (P=0.036)
      increased risk of recurrent miscarriage, respectively. Combined analysis of UCP2
      45-bp indel and leptin 2549 showed U0-L0 and U1-L0 variants to be at 2- and 3
      fold increased associative risk, respectively. Combined analysis of leptin 2549
      and adeponectin 276 showed L0-D0 and L0-D1 variants to be at 2- and 4-fold
      increased associative risk, respectively. The combination U1-L0-D1-A1-R1 was 4.39
      fold higher (P=0.0007) among recurrent miscarriage patients. In conclusion, the
      results highlight the role of the studied adipokine and UCP2 polymorphisms in
      recurrent miscarriage among the North Indian non-obese population. Pregnancy
      invokes a large shift in maternal metabolism. The normal concentrations of
      adipokines, which maintain the integrity of the hypothalamus-pituitary-gonadal
      axis, regular ovulatory processes and successful embryo implantation, are altered
      because of the influence of energy homeostasis, which in turn leads to fertility
      impairment and recurrent miscarriage of unknown aetiology. Recurrent miscarriage
      is reported in higher frequency among obese women. The UCP2 45-bp indel
      polymorphism and the adipokine gene polymorphisms namely leptin 2549 (C/A),
      adeponectin 276 (G/T), adeponectin 45 (T/G) and resistin 420 (C/G) have been
      shown to be associated with obesity. Most of the adipokine-related studies done
      previously have taken into consideration the metabolic function and obesity.
      However, there exist very few studies to evaluate the role of adipokines in non
      obese recurrent miscarriage with no cause of repeated pregnancy losses. The
      present study focused at evaluating the independent effect of these single
      nucleotide polymorphisms in non-obese women undergoing recurrent miscarriage.

PMID- 22995746
TI  - Comparable clinical outcomes and live births after single vitrified-warmed and
      fresh blastocyst transfer.
AB  - Selective single-blastocyst transfer (SBT) in fresh cycles has been effective in
      reducing multiple pregnancies. However, we do not know whether this successful
      strategy of fresh transfer cycles is suitable for cryopreserved cycles. The
      present study was undertaken to evaluate the feasibility and value of SBT in
      vitrified-warmed cycles. Clinical pregnancy rate (CPR) was similar with vitrified
      and fresh SBT (46.61% versus 52.15% respectively). Of the pregnant patients,
      monozygotic twin, miscarriage and ectopic pregnancy rates were similar with
      vitrified and fresh SBT. For the newborns, no significant difference was observed
      in live birth, low birthweight, premature delivery and birth defects rates
      between vitrified and fresh SBT. With respect to the quality of transferred
      blastocysts (from BB to AA), a similar CPR and miscarriage rate was obtained for
      both vitrified and fresh SBT when a similar blastocyst cohort graded >= 3BB was
      transferred. The data show that vitrified SBT is an effective means of reducing
      multiple pregnancy and that comparable clinical outcomes and live births are
      achieved if single blastocysts graded >= 3BB are transferred for both vitrified
      and fresh SBT. These data should encourage clinics to evaluate their embryo
      transfer policy and adopt vitrified SBT as everyday practice. Selective single
      blastocyst transfer in fresh cycles has been an effective method to reduce the
      multiple pregnancies. However, due to a lack of adequate studies, we do not know
      whether this successful strategy in fresh transfer cycles is suitable in
      cryopreserved cycles. The present study was undertaken to explore the feasibility
      and value of single-blastocyst transfer in vitrified-warmed cycles. We found that
      single-blastocyst transfer in vitrified-warmed cycles is an effective means of
      reducing multiple pregnancy, and comparable clinical outcomes and live births
      were achieved if single blastocysts graded >= 3BB were transferred for both
      vitrified-warmed and fresh blastocyst transfer. These data should encourage
      clinics to evaluate their embryo transfer policy and adopt single-blastocyst
      transfer in cryopreserved cycles as their everyday practice.

PMID- 22995747
TI  - Weight loss and vascular inflammatory markers in overweight women with and
      without polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular
      disease risk. The effect of weight loss on the vascular inflammatory markers
      plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA),
      soluble vascular cell adhesion molecule-1 (sVCAM-1) and intracellular adhesion
      molecule-1 (sICAM-1) is unknown. Overweight women with (n=14) and without (n=13)
      PCOS of comparable age and body mass index undertook an 8-week weight-loss
      programme. Women with PCOS had elevated PAI-1, sVCAM-1 and sICAM-1 before and
      after weight loss compared with the controls. For all women, sVCAM-1 (P=0.026)
      and sICAM-1 (P=0.04) decreased with weight loss. Women with PCOS have elevated
      inflammatory markers, which are partially reduced by weight loss.

PMID- 22995748
TI  - Endothelin-1: a key pathological factor in pre-eclampsia?
AB  - Endothelin (ET)-1 has been implicated in a diverse range of signalling events in
      a wide variety of target tissues. Given its potent vasoactive function and the
      prevalence of hypertension in pre-eclampsia, there has been extensive research on
      the role of ET-1 in this disorder. Indeed, ET-1 has been suggested to contribute
      to hypertension in pre-eclampsia. Recently, ET-1 has also been implicated in the
      induction of both oxidative stress and endoplasmic reticulum stress in pre
      eclampsia; each of which has been proposed to contribute to many of the clinical
      manifestations of this disorder. ET-1 has been shown to activate key signalling
      molecules that lead to induction of these stress pathways. The use of ET-receptor
      antagonists could block oxidative and endoplasmic reticulum stress. Hence,
      further research into the role of ET-1 in pre-eclampsia may lead to the
      development of possible strategies to circumvent these stress pathways and the
      associated pathology that occurs in pre-eclampsia. Endothelin (ET)-1 has been
      implicated in a diverse range of signalling events in a wide variety of target
      tissues. Given its potent vasoactive function and the prevalence of hypertension
      in pre-eclampsia, there has been extensive research on the role of ET-1 in this
      disorder. Indeed, ET-1 has been suggested to contribute to hypertension in pre
      eclampsia. Recently, ET-1 has also been implicated in the induction of both
      oxidative stress and endoplasmic reticulum stress in pre-eclampsia, each of which
      has been proposed to contribute to many of the clinical manifestations of this
      disorder. ET-1 has been shown to activate key signalling molecules that lead to
      induction of these stress pathways. The use of ET-receptor antagonists could
      block oxidative and endoplasmic reticulum stress. Hence, further research into
      the role of ET-1 in pre-eclampsia may lead to the development of possible
      strategies to circumvent these stress pathways and the associated pathology that
      occurs in pre-eclampsia.

PMID- 22995749
TI  - Normal birth following PGD for reciprocal translocation after serial
      vitrification of oocytes from a poor responder: a case report.
AB  - This case study reports the first successful birth outcome following
      preimplantation genetic diagnosis (PGD) for a chromosome translocation in embryos
      generated by serial vitrification of oocytes. A couple presented to the fertility
      clinic with 2 years of primary infertility. The woman was diagnosed with poor
      ovarian reserve and her partner was diagnosed with severe oligoteratozoospermia
      and the reciprocal translocation 46,XY,t(1;7)(p36.1;q11.23). Following
      counselling, the couple opted for serial vitrification of oocytes followed by
      PGD. A total of 31 oocytes were obtained in five egg collection cycles over a
      period of 12 months and 27 metaphase-II oocytes were vitrified. Nineteen of the
      27 vitrified oocytes survived warming: 14 oocytes from the vitrified group and
      three oocytes from the fresh cycle were fertilized by intracytoplasmic sperm
      injection. Eleven embryos, including three from the fresh cycle, were biopsied on
      day 3 post insemination. Fluorescence in-situ hybridization was performed for the
      specific chromosomes involved in translocation. Only two embryos from the
      cryopreservation cycles were diagnosed as normal/balanced, one of which was
      transferred on day 5 post insemination. A normal healthy female infant was born
      at week 42 of gestation.

PMID- 22995750
TI  - Cleavage kinetics analysis of human embryos predicts development to blastocyst
      and implantation.
AB  - Cleavage kinetics of human embryos is indicative of ability to develop to
      blastocyst and implant. Recent advances in time-lapse microscopy have opened new
      and important research opportunities. In this study involving infertile couples
      requiring standard IVF/intracytoplasmic sperm injection treatment, zygotes were
      cultured by integrated embryo-culture time-lapse microscopy to analyse cleavage
      times from the 2- to the 8-cell stages in relation to the ability to develop to
      blastocyst, expand and implant. In comparison to embryos arresting after 8-cell
      stage, times of cleavage to 7- and 8-cell stages of embryos developing to
      blastocyst were shorter (56.5 +/- 8.1 versus 58.8 +/- 10.4h, P=0.03 and 61.0 +/-
      9.4 versus 65.2 +/- 13.0 h, P=0.0008, respectively). In embryos developing to
      blastocyst, absence of blastocoele expansion on day 5 was associated with
      progressive cleavage delay. Implanting embryos developed to 8-cell stage in a
      shorter period compared with those unable to implant (54.9 +/- 5.2 and 58.0 +/-
      7.2h, respectively, P=0.035). In conclusion, cleavage from 2- to 8-cell stage
      occurs progressively earlier in embryos with the ability to develop to
      blastocyst, expand and implant. Conventional observation times on days 2 and 3
      are inappropriate for accurate embryo evaluation. The speed at which human
      embryos cleave is known to be suggestive of their ability to develop in vitro to
      the blastocyst stage and implant after transfer into the uterus. Recent advances
      in time-lapse microscopy, which allows acquisition of images every 15-20 min,
      have opened new and important research opportunities. In a retrospective study
      involving infertile couples requiring standard IVF or intracytoplasmic sperm
      injection treatment, fertilized oocytes were cultured by an integrated embryo
      culture time-lapse microscopy system in order to perform an analysis of cleavage
      times from the 2- to the 8-cell stage in relation to the ability to develop to
      blastocyst, expand and implant. In comparison to embryos arresting after the 8
      cell stage, times of cleavage to the 7- and 8-cell stage of embryos that
      developed to blastocyst were significantly shorter (56.5 +/- 8.1h versus 58.8 +/-
      10.4h and 61.0 +/- 9.4h versus 65.2 +/- 13.0 h, respectively). In embryos
      developing to the blastocyst stage, absence of blastocoele expansion on day 5 was
      associated with a progressive cleavage delay. Implanting embryos developed to the
      8-cell stage in a shorter period compared to those unable to implant (54.9 +/-
      5.2h and 58.0 +/- 7.2h, respectively, P=0.035). In conclusion, cleavage from the
      2- to the 8-cell stage occurs progressively earlier in embryos with the ability
      to develop to blastocyst, expand and implant. Conventional observation times on
      day 2 and 3 are appropriate for accurate embryo evaluation.

PMID- 22995751
TI  - Comment on 'Endovascular repair of abdominal aortic aneurysm does not improve
      early survival versus open repair in patients younger than 60 years'.

PMID- 22995752
TI  - Limited economic evidence of carotid artery stenosis diagnosis and treatment: a
      systematic review.
AB  - The objective of this article is to assess the availability and validity of
      economic evaluations of carotid artery stenosis (CS) diagnosis and treatment.
      DESIGN: Systematic review of economic evaluations of the diagnosis and treatment
      of CS. METHODS: Systematic review of full economic evaluations published in
      Medline and Google Scholar up until 28 February 2012. Based on economic
      checklists (Evers and Philips), the identified studies were classified as high,
      medium, or low quality. RESULTS: Twenty-three evaluations were identified. The
      study quality ranged from 26% to 84% of all achievable points (Evers). Seven
      studies were of high, eight of medium and eight of low quality. No comparison was
      made between carotid angioplasty and stenting (CAS) and best medical treatment
      (BMT). For subjects with severe stenosis, comparisons of carotid endarterectomy
      (CEA) and BMT were also missing. Three of five studies dealing with pre-operative
      imaging found that duplex Doppler ultrasound (US) was cost-effective compared
      with carotid angiogram (AG). CONCLUSIONS: There is a huge lack of high-quality
      studies and of studies that confirm published results. Also, for a given study
      quality, the most cost-effective treatment strategy is still unknown in some
      cases ('CAS' vs. 'BMT', 'US combined with magnetic resonance angiography
      supplemented with AG' vs. 'US combined with computer tomography angiography').

PMID- 22995753
TI  - Cumulative knee adductor load distinguishes between healthy and osteoarthritic
      knees--a proof of principle study.
AB  - Cumulative knee adductor load reflects repetitive exposures to medial knee
      loading that are encountered during daily activity. The purpose of this proof of
      principle study was to investigate whether cumulative knee adductor load
      distinguished between adults with and without knee osteoarthritis (OA). Thirty
      one adults with radiographic knee OA (53.2+/-6.1 years old) and 30 healthy adults
      (33.5+/-8.0 years old) participated. A non-normalized knee adduction moment
      waveform was calculated from gait data collected using a motion analysis system
      with synchronized force plate. The peak and impulse from knee adduction moment
      was calculated. Cumulative knee adductor load was the product of the knee
      adduction moment impulse during stance and the mean number of steps taken per
      day, measured with a uni-dimensional accelerometer. One thousand bootstrap t
      tests determined whether cumulative knee adductor load was at least as good as
      the peak knee adduction moment in discriminating between the healthy and OA
      groups. Cumulative knee adductor load was nearly two times larger in the knee OA
      compared to the healthy group (p=0.001). Cumulative knee adductor load was better
      than the peak knee adduction moment at discriminating between groups (p=0.04).
      This work provides evidence of validity for cumulative knee adductor load. In the
      calculation of cumulative loads, non-normalization of the adduction moment
      impulse to magnitude or time emphasized the importance of the total loads borne
      through the medial knee compartment during each step.

PMID- 22995754
TI  - The C-terminal domain of the Uup protein is a DNA-binding coiled coil motif.
AB  - The bacterial Uup protein belongs to the REG subfamily of soluble ATP-binding
      cassette (ABC) ATPases, and is implicated in precise excision of transposons. In
      Escherichia coli, the uup gene encodes a 72 kDa polypeptide that comprises two
      ABC domains, separated by a linker region, and a 12kDa C-terminal domain (CTD).
      Uup binds double-stranded DNA with no sequence specificity, and we previously
      demonstrated that the CTD domain is a crucial region that participates in DNA
      binding activity. We report herein the NMR structure of Uup CTD, consisting of an
      intramolecular antiparallel two-stranded coiled coil motif. Structural comparison
      with analogous coiled coil domains reveals that Uup CTD contains an atypical
      3(10)-helix in the alpha-hairpin region that contributes to the hydrophobic core.
      Using NMR titration experiments, we identified residues of the CTD domain
      involved in the binding to double-stranded DNA. These residues are located on two
      opposite surfaces at the base of the coiled coil, formed by the N- and C-terminal
      extremities, where a strictly conserved proline residue induces an overwinding of
      the coiled coil. Finally, preliminary analysis of NMR spectra recorded on
      distinct Uup constructs precludes a fully flexible positioning of the CTD domain
      in full-length Uup. These structural data are the first reported for a non-ATPase
      domain within ABC REG subfamily.

PMID- 22995755
TI  - Crosslinked linear polyethylenimine enhances delivery of DNA to the cytoplasm.
AB  - Crosslinked polyethylenimines (PEIs) have been frequently examined over the past
      decade since they can maintain the transfection efficiency of commercially
      available, 25k branched PEI, but exhibit less cytotoxicity. The argument is often
      made that the degradability of such polymers, generally synthesized with either
      disulfide or hydrolytically degradable crosslinkers, is critical to the high
      efficiency and low toxicity of the system. In this work, we present a crosslinked
      linear PEI (xLPEI) system in which either disulfide-responsive or non-degradable
      linkages are incorporated. As with previous systems, strong transfection
      efficiency in comparison with commercial standards was achieved with low
      cytotoxicity. However, these properties were shown to be present when either the
      degradable or non-degradable crosslinker was used. Uncomplexed polymer was
      demonstrated to be the critical factor determining transfection efficiency for
      these polymers, mediating efficient endosomal escape without signs of cell
      membrane damage. While several crosslinked PEI systems in the literature have
      demonstrated the effect of the disulfide moiety, this work demonstrates that
      disulfide-mediated unpackaging may not be as important as conventionally thought
      for some PEI systems.

PMID- 22995756
TI  - Knowledge and attitudes of doctors regarding the provision of mental health care
      in Doddaballapur Taluk, Bangalore Rural district, Karnataka.
AB  - BACKGROUND: Specialist mental health care is out of reach for most Indians. The
      World Health Organisation has called for the integration of mental health into
      primary health care as a key strategy in closing the treatment gap. However, few
      studies in India have examined medical practitioners' mental health-related
      knowledge and attitudes. This study examined these facets of service provision
      amongst doctors providing primary health care in a rural area of Karnataka is
      Southern India. METHODS: A mental health knowledge and attitudes questionnaire
      was self- administered by participants. The questionnaire consisted of four
      sections; 1) basic demographics and practice information, 2) training in mental
      health, 3) knowledge of mental health, and self-perceived competence in providing
      mental health care, and 4) attitudes towards mental health. Data was analysed
      quantitatively, primarily using descriptive statistics. RESULTS: This study
      recruited 46 participants. The majority of participants (69.6%) felt competent in
      providing mental health services to their patients. However, there was a
      substantial level of endorsement for several statements that reflected negative
      attitudes. Almost one third of participants (28.0%) had not received any training
      in providing mental health care. Whilst three-quarters of participants correctly
      identified depression (76.1%) and psychosis (76.1%) in a vignette, fewer were
      able to name three common signs and symptoms of depression (50.0%) and psychosis
      (28.3%). CONCLUSIONS: Integrating mental health into primary health care requires
      evidence-based up-skilling programs. Doctors in this study desired such training
      and would benefit from it, with a focus on both depth of knowledge and uncovering
      stigmatising attitudes towards people with mental health problems.

PMID- 22995757
TI  - Endoscopic resection of esthesioneuroblastoma.
AB  - Esthesioneuroblastoma, or olfactory neuroblastoma, is an uncommon malignant tumor
      arising in the upper nasal cavity. Surgical approaches to this and other
      sinonasal malignancies involving the anterior skull base have traditionally
      involved craniofacial resections. Over the past 10 years to 15 years, there have
      been advances in endoscopic approaches to skull base pathologies, including
      malignant tumors. In this study, we review our experience with purely endoscopic
      approaches to esthesioneuroblastomas. Between January 2005 and February 2012, 11
      patients (seven men and four women, average age 53.3 years) with
      esthesioneuroblastoma were treated endoscopically. Nine patients presented with
      newly diagnosed disease and two were treated for tumor recurrence. The modified
      Kadish staging was: A, two patients (18.2%); B, two patients (18.2%); C, five
      patients (45.5%); and D, two patients (18.2%). All patients had a complete
      resection with negative intraoperative margins. Three patients had 2-deoxy-2
      ((18)F)fluoro-d-glucose avid neck nodes on their preoperative positron emission
      tomography-CT scan. These patients underwent neck dissections; two had positive
      neck nodes. Perioperative complications included an intraoperative hypertensive
      urgency and pneumocephalus in two different patients. Mean follow-up was over 28
      months and all patients were free of disease. This series adds to the growing
      experience of purely endoscopic surgical approaches in the treatment of skull
      base tumors including esthesioneuroblastoma. Longer follow-up on larger numbers
      of patients is required to clarify the utility of purely endoscopic approaches in
      the management of this malignant tumor.

PMID- 22995758
TI  - Towards an integrated molecular and clinical strategy to predict early recurrence
      in surgically resected non-functional pituitary adenomas.
AB  - Pituitary adenomas (PA) are histologically benign tumors of the sella that are
      capable of recurrence following resection. No mechanism exists to predict
      accurately the risk of recurrence in patients with PA following successful gross
      total surgical resection. We used microarray-based gene expression profiling to
      search for genotypically distinct subgroups of non-functional PA associated with
      the early recurrent phenotype. Rigorous phenotypic controls were used to select
      four patients with PA with early (<12 months) recurrence and seven patients with
      non-recurrent PA for comparative molecular analysis. Seventy genes with
      differential expression patterns between the phenotypic groups were identified,
      although this required some relaxation of rigid multiple-testing corrections.
      While some of these genes may therefore represent statistical false discoveries
      attributable to limited sample size, the CHL1 gene has a differential expression
      patterns that suggests a potential role as a predictor of recurrence phenotype.
      Transcriptome-level differences between early recurrent and non-recurrent non
      functional PA appear to be subtle, although CHL1 expression may be a candidate
      for further study as a class discriminator. This suggests two possibilities with
      regard to recurrence; (i) that microscopic residual disease unidentifiable either
      by the surgeon or by current neuroimaging strategies may serve as a focus for
      early recurrence or that biological differences in recurrence phenotypes may
      occur outside of the transcriptome. These findings are useful for focusing future
      investigations into the clinical and biological mechanisms of PA recurrence as
      well as for development of strategies designed to predict prospectively these
      recurrence phenotypes.

PMID- 22995759
TI  - A single centre study of the treatment of relapsed primary central nervous system
      lymphoma (PCNSL) with single agent temozolomide.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare form of extra-nodal non
      Hodgkin lymphoma. Although recommendations for first-line treatment usually
      incorporate high-dose methotrexate, there is substantial heterogeneity in the
      types of salvage therapies used at relapse. Phase II data supported the use of
      temozolomide as a well-tolerated treatment modality in this setting. Therefore,
      we reviewed the treatment and outcomes of patients with relapsed PCNSL who were
      treated with salvage temozolomide at our institution. Seven patients were treated
      with salvage temozolomide between January 2000 and May 2011. The objective
      response rate was 14%. Progression-free survival was 2 months (95% confidence
      interval [CI]: 0-5.9) and median overall survival was 4 months (95% CI: 0-13).
      Toxicity was mild, with one episode of grade 3 neutropenia during 25 cycles of
      chemotherapy. Although these results are consistent with previous phase II
      results, the outcomes for these patients remain extremely poor. The low toxicity
      of temozolomide raises the possibility of combining temozolomide with other
      chemotherapeutic agents or targeted agents in future clinical trials.

PMID- 22995760
TI  - Use of a micromanipulator system (NeuRobot) in endoscopic neurosurgery.
AB  - NeuRobot, a micromanipulator system with a rigid neuroendoscope and three
      micromanipulators, was developed for less invasive and telecontrolled
      neurosurgery. This system can be used to perform sophisticated surgical
      procedures through a small, 10-mm-diameter, window. The present study was
      performed to evaluate the feasibility of using NeuRobot in neuroendoscopy. Four
      different intraventricular neurosurgical procedures were simulated in three fixed
      cadaver heads using NeuRobot: (1) fenestration of the floor of the third
      ventricle; (2) fenestration of the septum pellucidum; (3) biopsy of the thalamus;
      and (4) biopsy of the choroid plexus of the lateral ventricle. Each procedure
      required less than 2 min, and all procedures were performed accurately. After
      these surgical simulations, a third ventriculostomy was carried out safely and
      adequately in a patient with obstructive hydrocephalus due to a midbrain venous
      angioma. Our results confirmed that NeuRobot is applicable to lesions in which
      conventional endoscopic neurosurgery is indicated. Furthermore, NeuRobot can
      perform more complex surgical procedures than a conventional neuroendoscope
      because of its maneuverability and stability. NeuRobot will become a useful
      neurosurgical tool for dealing with lesions that are difficult to treat by
      conventional neuroendoscopic surgery.

PMID- 22995761
TI  - Highlights of the conference 'The hidden side of DNA profiles: Artifacts, errors
      and uncertain evidence'.

PMID- 22995762
TI  - Relative validity of an FFQ to estimate daily food and nutrient intakes for
      Chilean adults.
AB  - OBJECTIVE: FFQ are commonly used to rank individuals by their food and nutrient
      intakes in large epidemiological studies. The purpose of the present study was to
      develop and validate an FFQ to rank individuals participating in an ongoing
      Prospective Urban and Rural Epidemiological (PURE) study in Chile. DESIGN: An FFQ
      and four 24 h dietary recalls were completed over 1 year. Pearson correlation
      coefficients, energy-adjusted and de-attenuated correlations and weighted kappa
      were computed between the dietary recalls and the FFQ. The level of agreement
      between the two dietary assessment methods was evaluated by Bland-Altman
      analysis. SETTING: Temuco, Chile. SUBJECTS: Overall, 166 women and men enrolled
      in the present study. One hundred men and women participated in FFQ development
      and sixty-six individuals participated in FFQ validation. RESULTS: The FFQ
      consisted of 109 food items. For nutrients, the crude correlation coefficients
      between the dietary recalls and FFQ varied from 0.14 (protein) to 0.44 (fat).
      Energy adjustment and de-attenuation improved correlation coefficients and almost
      all correlation coefficients exceeded 0.40. Similar correlation coefficients were
      observed for food groups; the highest de-attenuated energy adjusted correlation
      coefficient was found for margarine and butter (0.75) and the lowest for potatoes
      (0.12). CONCLUSIONS: The FFQ showed moderate to high agreement for most nutrients
      and food groups, and can be used to rank individuals based on energy, nutrient
      and food intakes. The validation study was conducted in a unique setting and
      indicated that the tool is valid for use by adults in Chile.

PMID- 22995763
TI  - Is juvenile dermatomyositis a different disease in children up to three years of
      age at onset than in children above three years at onset? A retrospective review
      of 23 years of a single center's experience.
AB  - BACKGROUND: We tested the hypothesis that the course and outcome of juvenile
      dermatomyositis (JDM) in children seen at one center with the JDM disease onset
      at or below three years of age is different from that in the children with
      disease onset at greater than three years of age. METHODS: Institutional Review
      Board approval was obtained to retrospectively review the charts of 78 patients
      from age 0-18 years with JDM seen in the pediatric rheumatology clinic at
      Nationwide Children's Hospital in Columbus, Ohio over the past 23 years from
      January 1988. The diagnosis was made by the treating pediatric rheumatologist.
      Not all the patients met the Bohan and Peter criteria, as muscle biopsy and EMG
      were not always performed and we utilized a modified JDM criteria. The data
      regarding disease course and outcome were collected as of the last clinic follow
      up or to July 1, 2010. We used the Wilcoxon Two-Sample test to compare numerical
      variables between two age groups, and used logistic regression to compare
      categorical variables between two age groups in SAS 9.1.3. Minitab-16 was used to
      calculate various mean, median, modes, standard deviations and range. For
      survival analysis, we used Kaplan-Meier method with log-rank test. RESULTS: The
      mean age of onset in the two groups at Nationwide Children's Hospital was 27
      months and 91 months. The mean times between onset of symptoms to diagnosis in
      the younger and older age groups was 5.6 months and 4.5 months, respectively, not
      a statistically significant difference. The younger onset group had more females
      (p=0.05) and their disease onset occurred less frequently during the typical
      winter-spring seasons (p=0.031). The younger onset group was more likely to have
      a preceding fever (p=0.029) and family history of autoimmune diseases (p=0.012).
      The younger onset group was less likely to have heliotrope rash (p=0.04),
      Gottron's sign (p=0.049), capillary loop abnormalities (p=0.010), or elevations
      in creatine kinase (CK, p=0.022), aspartate aminotransferase (AST, p=0.021) or
      aldolase (p=0.035). The younger onset group was treated less often with pulse
      methylprednisolone at diagnosis (p=0.043) and less often with hydroxychloroquine
      (p=0.035). There were no differences between the two groups regarding initial
      oral steroid dose (p=0.8017), number of patients who received methotrexate at
      diagnosis (p=0.709), and the number who ever received other immunosuppressants
      (p=0.323). The mean and maximum duration (mean duration 24.3 months vs. 35.2
      months, maximum duration 51 vs. 124 months in younger and older onset group
      respectively) of methotrexate therapy, and the mean and maximum duration of oral
      steroid therapy (Mean duration 16.8 months vs. 33.3 months, maximum duration 50
      vs. 151 months in younger and older onset group respectively), was shorter in the
      younger group. The younger onset patients were less likely to have active disease
      at 5 years (9% vs. 35.7%, p=0.015) and 10 years post-diagnosis (9% vs. 45.1%,
      p=0.011, Table 7). The younger patients were less likely to have osteonecrosis
      (p=0.023). Two disease-related deaths occurred in the younger group, none in the
      older group. The results of the survival analysis showed that the difference
      between the age groups was statistically significant (p < 0.012). The sex and
      race were not significant (p> 0.26 and p>0.95, respectively). CONCLUSIONS: There
      were significant differences between JDM patients with disease onset at or below
      age three years at our center, compared to their older counterparts. Younger
      patients in our cohort had fewer typical findings at diagnosis and a milder
      disease course without needing as long a duration of corticosteroids and
      immunosuppression. Patients with a younger onset had a higher mortality rate but
      mortalities were unusual and numbers small. The younger group had a similar
      complication rate compared to the older onset patients, except for osteonecrosis
      which was higher in the older onset group. These findings differ from the
      previous reports that a younger age of onset in JDM is often associated with a
      more severe disease, as results at our center suggest that children with younger
      onset JDM appear to be atypical but may do well compared to the older JDM
      patients.

PMID- 22995764
TI  - Time-varying effects of smoking quantity and nicotine dependence on adolescent
      smoking regularity.
AB  - BACKGROUND: Little is known about time-varying effects of smoking quantity and
      nicotine dependence on the regularity of adolescent smoking behavior. METHODS:
      The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking
      Patterns Study which followed adolescent smokers over 5 assessment waves spanning
      48 months. Participants included former experimenters (smoked <100
      cigarettes/lifetime but did not smoke in past 90 days), recent experimenters
      (smoked <100 cigarettes/lifetime and smoked in past 90 days), and current smokers
      (smoked >100 cigarettes/lifetime and smoked in past 30 days). Mixed-effects
      regression models were run to examine the time-varying effects of smoking
      quantity and nicotine dependence on regularity of smoking behavior, as measured
      by number of days smoked. RESULTS: Smoking quantity and nicotine dependence were
      each found to be significantly associated with regularity of adolescent smoking
      and the size of each effect exhibited significant variation over time. The effect
      of smoking quantity decreased across time for each smoking group, while the
      effect of nicotine dependence increased across time for former and recent
      experimenters. By the 48-month follow-up, the effects of smoking quantity and
      nicotine dependence had each stabilized across groups. CONCLUSIONS: This study
      reveals that smoking quantity and nicotine dependence are not static risk factors
      for the development of more regular smoking patterns. At low levels of smoking
      when nicotine dependence symptoms are less common, smoking quantity is a stronger
      predictor of increased regularity of smoking, while for more experienced smokers,
      nicotine dependence predicts further increases in regularity.

PMID- 22995765
TI  - Genetic analysis of AUTS2 as a susceptibility gene of heroin dependence.
AB  - BACKGROUND: Both alcoholism and heroin dependence are common substance use
      disorders with a high genetic basis. A recent genetic study reported that the
      autism susceptibility candidate 2 gene (AUTS2) was involved in regulating the
      alcohol drinking behavior. In our previous total gene expression profiling study,
      we found that the AUTS2 transcript was significantly down-regulated in
      lymphoblastoid cell lines (LCL) in heroin dependent individuals compared with
      control subjects, which prompted us to investigate whether AUTS2 is associated
      with heroin dependence. METHODS: We compared the AUTS2 transcript level of LCL
      between 124 heroin dependent males and 116 control males using real-time
      quantitative PCR, and conducted a genetic association study of the rs6943555 of
      AUTS2 with heroin dependence using a sample of 546 heroin dependent males and 373
      control males. RESULTS: We first verified that the average transcript level of
      AUTS2 in the heroin dependent group was significantly lower than that in the
      control group (p=0.017). In the genetic association analysis, we found that AA
      homozygotes of rs6943555 were significantly over-represented in the heroin
      dependent subjects compared with the control subjects (odds ratio=1.7, 95%
      confidence interval: 1.08-2.74, p=0.017). Analyzing the sample from the AUTS2
      transcript experiment, we found that AA carriers (n=19) had significantly lower
      AUTS2 mRNA levels in their LCL compared to TT carriers (n=97, p=0.002) and AT
      carriers (n=91, p=0.005). CONCLUSIONS: Our data indicate that the AUTS2 gene
      might be associated with heroin dependence, and reduced AUTS2 gene expression
      might confer increased susceptibility to heroin dependence.

PMID- 22995767
TI  - Laparoscopic cystectomy for the treatment of benign ovarian cysts in children: an
      analysis of 21 cases.
AB  - STUDY OBJECTIVE: To evaluate the outcomes of treatment with minimal invasive
      surgery in children with benign ovarian cysts. DESIGN: Retrospective chart
      review. SETTINGS: Maternity and children hospital. PATIENTS: Between May 2007 and
      May 2011, 21 children were treated by laparoscopic method for ovarian cysts at
      our clinic. The age, symptoms, ultrasonographic findings, operation records and
      follow-up times were retrospectively evaluated. RESULTS: The mean age was 13.2
      years. One patient presented with findings of torsion and another presented with
      findings of rupture; both were urgently operated on. The other patients presented
      with intermittent abdominal pain and were operated on under elective basis. The
      mean cyst size was 8.4 cm (5-13 cm). One patient with necrotic ovary and salpinx
      due to torsion underwent salpingo-oophorectomy while the others were administered
      ovary-preserving cystectomy. Only 4 patients required iv paracetamol as an
      analgesic in the postoperative period. Two patients were discharged on the second
      postoperative day while the remaining 19 patients were discharged on the first
      postoperative day. During a mean follow-up of 14 months, no recurrence was seen
      in this period. Cosmetic appearance was good in all patients. CONCLUSION: The
      authors demonstrated that laparoscopic cystectomy was a technically feasible and
      safe method in the treatment of benign ovarian cysts, associated with short
      hospitalization, minimal analgesic requirement, and a good cosmetic appearance.

PMID- 22995766
TI  - Psychiatric diagnoses among quitters versus continuing smokers 3 years after
      their quit day.
AB  - BACKGROUND: People with psychiatric disorders are more likely to smoke and smoke
      more heavily than the general population, and they suffer disproportionally from
      smoking-related illnesses. However, little is known about how quitting versus
      continuing to smoke affects mental health and the likelihood of developing a
      psychiatric diagnosis. This study used data from a large prospective clinical
      trial to examine the relations of smoking cessation success with psychiatric
      diagnoses 1 and 3 years after the target quit day. METHODS: This study enrolled
      1504 smokers (83.9% white; 58.2% female) in a cessation trial that involved the
      completion of the Composite International Diagnostic Interview to assess
      psychiatric diagnoses and biochemical confirmation of point-prevalence abstinence
      at Baseline and Years 1 and 3. RESULTS: Regression analyses showed that, after
      controlling for pre-quit (past-year) diagnoses, participants who were smoking at
      the Year 3 follow-up were more likely to have developed and maintained a
      substance use or major depressive disorder by that time than were individuals who
      were abstinent at Year 3. CONCLUSIONS: Quitting smoking does not appear to
      negatively influence mental health in the long-term and may be protective with
      respect to depression and substance use diagnoses; this should encourage smokers
      to make quit attempts and encourage clinicians to provide cessation treatment.

PMID- 22995768
TI  - Explaining health care professionals' resistance to implement Diagnosis Related
      Groups: (No) benefits for society, patients and professionals.
AB  - BACKGROUND: Effective health system reform requires support from health care
      professionals. However, many studies show an increasing discontent among health
      care professionals toward certain government policies. When professionals resist
      implementing policies, this may have serious consequences for policy
      effectiveness. OBJECTIVE: To develop and test a model for explaining resistance
      of health professionals to implement policies, based on three dimensions:
      societal benefits (such as improving efficiency), patient benefits (such as
      improving quality for individual patients) and personal benefits for
      professionals (for example increased income or fewer administrative burdens).
      METHODS: We conduct a survey among 1317 Dutch psychologists, psychotherapists and
      psychiatrists in 2010 who had to implement a new policy: Diagnosis Related Groups
      (DRGs). The dependent variable is professionals' resistance to implement these
      DRGs. As independent variables we develop scales to measure perceived societal
      benefits, patient benefits and personal benefits. Socio-demographic variables are
      also included. RESULTS: The model worked adequately in that the three benefit
      dimensions, together with control variables, explained 43% of the variance in
      resistance to implement DRGs. Results indicate that health professionals were
      overall quite resistant towards the policy. The main reason was widespread belief
      that DRGs neither contribute to care quality nor help to control costs (low
      societal benefits). Resistance can also be explained by fears for one's personal
      status, income, and administrative burdens. Professionals furthermore doubt
      whether the policy is beneficial for patients, although this dimension is the
      least influential, which was unexpected. Perceived effects on patient choice,
      furthermore, do not contribute to willingness or resistance to work with DRGs.
      These insights can help in understanding why health care professionals embrace or
      resist the implementation of particular policies.

PMID- 22995769
TI  - Intrinsic and extrinsic motivations in primary care: an explanatory study among
      French general practitioners.
AB  - BACKGROUND: Like many other OECD nations, France has implemented a pay-for
      performance (P4P) model in primary care. However, the benefits have been debated,
      particularly regarding the possibly undesirable effects of extrinsic motivation
      (EM) on intrinsic motivation (IM). OBJECTIVE: To examine the relationship between
      French GPs' IM and EM based on an intrinsic motivation composite score (IMCS)
      developed for this purpose. If a negative relationship is found, P4P schemes
      could have side effects on GPs' IM that is a key determinant of quality of care.
      METHOD: From data on 423 GPs practicing in a region of France, IM indicators are
      selected using a multiple correspondence analysis and aggregated from a
      multilevel model. RESULTS: Several doctors' characteristics have significant
      impacts on IMCS variability, especially group practice and salaried practice.
      Qualitative EM variables are negatively correlated with the IMCS: GPs who report
      not being satisfied with their income or feeling "often" constrained by patients'
      requests in terms of consultations length and office appointments obtain a lower
      mean IMCS than other GPs. CONCLUSION: Our results provide a cautionary message to
      regulators who should take into account the potential side effects of increasing
      EM through policies such as P4P.

PMID- 22995770
TI  - The next generation proteasome inhibitors carfilzomib and oprozomib activate
      prosurvival autophagy via induction of the unfolded protein response and ATF4.
AB  - The proteasome inhibitor bortezomib has shown remarkable clinical success in the
      treatment of multiple myeloma. However, the efficacy and mechanism of action of
      bortezomib in solid tumor malignancies is less well understood. In addition, the
      use of this first-in-class proteasome inhibitor is limited by several factors,
      including off-target effects that lead to adverse toxicities. We recently
      reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class
      proteasome inhibitors with higher specificities and reduced toxicities, against
      head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently
      inhibit HNSCC cell survival and the growth of HNSCC tumors. Both compounds
      promote upregulation of proapoptotic BIK and antiapoptotic MCL1, which serves to
      mediate and attenuate, respectively, the killing activities of these proteasome
      inhibitors. Both compounds also induce complete autophagic flux that is partially
      dependent on activation of the unfolded protein response (UPR) and upregulation
      of ATF4. Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell
      survival. Our study indicates that the therapeutic benefit of these promising
      proteasome inhibitors may be improved by inhibiting MCL1 expression or autophagy.

PMID- 22995771
TI  - Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties.
AB  - A series of tetracyclic nitrofuran isoxazoline anti-tuberculosis agents was
      designed and synthesized to improve the pharmacokinetic properties of an initial
      lead compound, which had potent anti-tuberculosis activity but suffered from poor
      solubility, high protein binding and rapid metabolism. In this study, structural
      modifications were carried on the outer phenyl and piperidine rings to introduce
      solubilizing and metabolically blocking functional groups. The compounds
      generated were evaluated for their in vitro antitubercular activity, bacterial
      spectrum of activity, solubility, permeability, microsomal stability and protein
      binding. Pharmacokinetic profiles for the most promising candidates were then
      determined. Compounds with phenyl morpholine and pyridyl morpholine outer rings
      were found to be the most potent anti-tuberculosis agents in the series. These
      compounds retained a narrow antibacterial spectrum of activity, with weak anti
      Gram positive and no Gram negative activity, as well as good activity against non
      replicating Mycobacterium tuberculosis in a low oxygen model. Overall, the
      addition of solubilizing and metabolically blocked outer rings did improve
      solubility and decrease protein binding as designed. However, the metabolic
      stability for compounds in this series was generally lower than desired. The best
      three compounds selected for in vivo pharmacokinetic testing all showed high oral
      bioavailability, with one notable compound showing a significantly longer half
      life and good tolerability supporting its further advancement.

PMID- 22995772
TI  - Structure-activity relationship study of nitrosopyrimidines acting as antifungal
      agents.
AB  - The design, synthesis, in vitro evaluation, and conformational study of
      nitrosopyrimidine derivatives acting as antifungal agents are reported. Different
      compounds structurally related with 4,6-bis(alkyl or arylamino)-5
      nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines have
      displayed a significant antifungal activity against human pathogenic strains. In
      this paper, we report a new group of nitrosopyrimidines acting as antifungal
      agents. Among them, compounds 2a, 2b and 15, the latter obtained from a molecular
      modeling study, exhibited antifungal activity against Candida albicans, Candida
      tropicalis and Cryptococcus neoformans. We have performed a conformational and
      electronic analysis on these compounds by using quantum mechanics calculations in
      conjunction with Molecular Electrostatic Potentials (MEP) obtained from B3LYP/6
      31G(d) calculations. Our experimental and theoretical results have led us to
      identify a topographical template which may provide a guide for the design of new
      nitrosopyrimidines with antifungal effects.

PMID- 22995773
TI  - Healing hearts and minds: can antidepressants repair the heart?

PMID- 22995774
TI  - GM in the media.

PMID- 22995775
TI  - Microscopic colitis patients have increased proportions of Ki67(+) proliferating
      and CD45RO(+) active/memory CD8(+) and CD4(+)8(+) mucosal T cells.
AB  - BACKGROUND: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic
      inflammatory bowel disorders of unknown etiology. This study investigated
      phenotypic characteristics of the mucosal lymphocytes in CC and LC. METHODS:
      Lamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal
      biopsies from CC (n=7), LC (n=6), as well as LC or CC patients in
      histopathological remission, (LC-HR) (n=6) and CC-HR (n=4) and non-inflamed
      controls (n=10) were phenotypically characterized by four-color flow cytometry.
      RESULTS: The proportions of CD8(+) IELs were increased in CC and LC (p<0.01)
      compared to controls. Increased proportions of CD45RO(+)CD8(+) IELs and LPLs were
      observed in LC and even more in CC patients (p<0.01). Both CC (p<0.05) and LC
      patients had elevated proportions of CD4(+)8(+) IELs and LPLs compared to
      controls. The proportions of CD45RO(+) cells were increased in CD4(+)8(+) IELs
      and LPLs (p<0.05) in CC and LC patients compared to controls. Both CC (p<0.05)
      and LC patients had higher proportions of Ki67(+)CD8(+) IELs and LPLs compared to
      controls. In contrast, decreased proportions of CD4(+) LPLs were observed in CC
      and LC as well as CD4(+) IELs in LC compared to controls. Increased proportions
      of Ki67(+)CD4(+) IELs and LPLs (p<0.05) were observed in CC and LC patients. CC
      HR but not LC-HR patients demonstrated normalized proportions of both IELs and
      LPLs compared to CC and LC patients respectively. CONCLUSION: LC and CC patients
      have differences in mucosal lymphocyte subsets, with increased proportions of
      Ki67(+) and CD45RO(+) CD8(+) and CD4(+)8(+) mucosal T cells.

PMID- 22995776
TI  - Shared electrophysiology mechanisms of body ownership and motor imagery.
AB  - Although we feel, see, and experience our hands as our own (body or hand
      ownership), recent research has shown that illusory hand ownership can be induced
      for fake or virtual hands and may be useful for neuroprosthetics and brain
      computer interfaces. Despite the vast amount of behavioral data on illusory hand
      ownership, neuroimaging studies are rare, in particular electrophysiological
      studies. Thus, while the neural systems underlying hand ownership are relatively
      well described, the spectral signatures of body ownership as measured by
      electroencephalography (EEG) remain elusive. Here we induced illusory hand
      ownership in an automated, computer-controlled manner using virtual reality while
      recording 64-channel EEG and found that illusory hand ownership is reflected by a
      body-specific modulation in the mu-band over fronto-parietal cortex. In a second
      experiment in the same subjects, we then show that mu as well as beta-band
      activity in highly similar fronto-parietal regions was also modulated during a
      motor imagery task often used in paradigms employing non-invasive brain-computer
      interface technology. These data provide insights into the electrophysiological
      brain mechanisms of illusory hand ownership and their strongly overlapping
      mechanisms with motor imagery in fronto-parietal cortex. They also highlight the
      potential of combining high-resolution EEG with virtual reality setups and
      automatized stimulation protocols for systematic, reproducible stimulus
      presentation in cognitive neuroscience, and may inform the design of non-invasive
      brain-computer interfaces.

PMID- 22995778
TI  - Manganese enhanced MRI in rat hippocampus: a correlative study with synchrotron X
      ray microprobe.
AB  - Manganese enhanced MRI (MEMRI) offers many possibilities such as tract tracing
      and functional imaging in vivo. Mn is however neurotoxic and may induce symptoms
      similar to those associated with Parkinson's disease (manganism). The mechanisms
      of Mn-induced neurotoxicity are not clear. In this study, we combine synchrotron
      X-ray fluorescence microprobe (SR-XRF) and MEMRI techniques to investigate
      spatial distribution of Mn within the rat hippocampus and how Mn interacts with
      Ca, Fe and Zn at a cellular level. Images were acquired in the rat hippocampus
      (n=23) and using two injection routes: intra-cerebral (MnCl(2): 50 mM, 10 MUL)
      and intra-peritoneal (MnCl(2): 100 mM, 30 mg/kg). For both injection routes, Mn
      is found in dentate gyrus and in CA3: control: 2.5 +/- 1.6, intra-peritoneal: 5.0
      +/- 2.4, and intra-cerebral: 25.1 +/- 9.2 MUg/g. Mn follows Zn distribution and
      has a negative impact on the total amount of Zn and Fe. The Mn-enhanced MRI
      contrast is well correlated with the total Mn amount measured with SR-XRF
      (R(2)=0.93; p<0.002). After intra-cerebral injection, the hippocampal fissure is
      found to accumulate a large amount of Mn and yields a hypointense MRI signal,
      which may be ascribed to a reduction in T2. This study shows that SR-XRF is well
      suited to investigate Mn distribution at a mesoscale and that MRI is sensitive to
      low Mn concentrations. As perturbations in metal homeostasis may alter brain
      function, the injected dose of Mn in MEMRI studies needs to be carefully adjusted
      to obtain reliable functional information.

PMID- 22995777
TI  - Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI
      with 18F-FAHA.
AB  - Epigenetic modifications mediated by histone deacetylases (HDACs) play important
      roles in the mechanisms of different neurologic diseases and HDAC inhibitors
      (HDACIs) have shown promise in therapy. However, pharmacodynamic profiles of many
      HDACIs in the brain remain largely unknown due to the lack of validated methods
      for noninvasive imaging of HDAC expression-activity. In this study, dynamic
      PET/CT imaging was performed in 4 rhesus macaques using [(18)F]FAHA, a novel HDAC
      substrate, and [(18)F]fluoroacetate, the major radio-metabolite of [(18)F]FAHA,
      and fused with corresponding MR images of the brain. Quantification of
      [(18)F]FAHA accumulation in the brain was performed using a customized dual
      tracer pharmacokinetic model. Immunohistochemical analyses of brain tissue
      revealed the heterogeneity of expression of individual HDACs in different brain
      structures and cell types and confirmed that PET/CT/MRI with [(18)F]FAHA reflects
      the level of expression-activity of HDAC class IIa enzymes. Furthermore,
      PET/CT/MRI with [(18)F]FAHA enabled non-invasive, quantitative assessment of
      pharmacodynamics of HDAC inhibitor SAHA in the brain.

PMID- 22995779
TI  - The neural correlates of velocity processing during the observation of a
      biological effector in the parietal and premotor cortex.
AB  - While there have been several studies investigating the neural correlates of
      action observation associated with hand grasping movements, comparatively little
      is known about the neural bases of observation of reaching movements. In two
      experiments, using functional magnetic resonance imaging (fMRI), we defined the
      cortical areas encoding reaching movements and assessed their sensitivity to
      biological motion and to movement velocity. In the first experiment, participants
      observed video-clips showing either a biological effector (an arm) or a non
      biological object (rolling cylinder) reaching toward a target with a biological
      and a non-biological motion, respectively. In the second experiment, participants
      observed video-clips showing either a biological effector (an arm) or a non
      biological object (an arrow) reaching toward a target with the same biological
      motion profiles. The results of the two experiments revealed activation of
      superior parietal and dorsal premotor sites during observation of the biological
      motion only, independent of whether it was performed by a biological effector
      (reaching arm) or a non-biological object (reaching arrow). These areas were not
      activated when participants observed the non-biological movement (rolling
      cylinder). To assess the responsiveness of parietal and frontal sites to movement
      velocity, the fMRI repetition-suppression (RS) technique was used, in which
      movement was shown with same or different velocities between consecutive videos,
      and observation of identical stimuli was contrasted with observation of different
      stimuli. Regions of interest were defined in the parietal and frontal cortices,
      and their response to stimulus repetition was analyzed (same vs. different
      velocities). The results showed an RS effect for velocity only during the
      observation of movements performed by the biological effector and not by the non
      biological object. These data indicate that dorsal premotor and superior parietal
      areas represent a neural substrate involved in the encoding of reaching movements
      and that their responsiveness to movement velocity of a biological effector could
      be instrumental to the discrimination of movements performed by others.

PMID- 22995780
TI  - Novel artefact removal algorithms for co-registered EEG/fMRI based on selective
      averaging and subtraction.
AB  - Co-registered EEG and functional MRI (EEG/fMRI) is a potential clinical tool for
      planning invasive EEG in patients with epilepsy. In addition, the analysis of
      EEG/fMRI data provides a fundamental insight into the precise physiological
      meaning of both fMRI and EEG data. Routine application of EEG/fMRI for
      localization of epileptic sources is hampered by large artefacts in the EEG,
      caused by switching of scanner gradients and heartbeat effects. Residuals of the
      ballistocardiogram (BCG) artefacts are similarly shaped as epileptic spikes, and
      may therefore cause false identification of spikes. In this study, new ideas and
      methods are presented to remove gradient artefacts and to reduce BCG artefacts of
      different shapes that mutually overlap in time. Gradient artefacts can be removed
      efficiently by subtracting an average artefact template when the EEG sampling
      frequency and EEG low-pass filtering are sufficient in relation to MR gradient
      switching (Goncalves et al., 2007). When this is not the case, the gradient
      artefacts repeat themselves at time intervals that depend on the remainder
      between the fMRI repetition time and the closest multiple of the EEG acquisition
      time. These repetitions are deterministic, but difficult to predict due to the
      limited precision by which these timings are known. Therefore, we propose to
      estimate gradient artefact repetitions using a clustering algorithm, combined
      with selective averaging. Clustering of the gradient artefacts yields cleaner EEG
      for data recorded during scanning of a 3T scanner when using a sampling frequency
      of 2048 Hz. It even gives clean EEG when the EEG is sampled with only 256 Hz.
      Current BCG artefacts-reduction algorithms based on average template subtraction
      have the intrinsic limitation that they fail to deal properly with artefacts that
      overlap in time. To eliminate this constraint, the precise timings of artefact
      overlaps were modelled and represented in a sparse matrix. Next, the artefacts
      were disentangled with a least squares procedure. The relevance of this approach
      is illustrated by determining the BCG artefacts in a data set consisting of 29
      healthy subjects recorded in a 1.5 T scanner and 15 patients with epilepsy
      recorded in a 3 T scanner. Analysis of the relationship between artefact
      amplitude, duration and heartbeat interval shows that in 22% (1.5T data) to 30%
      (3T data) of the cases BCG artefacts show an overlap. The BCG artefacts of the
      EEG/fMRI data recorded on the 1.5T scanner show a small negative correlation
      between HBI and BCG amplitude. In conclusion, the proposed methodology provides a
      substantial improvement of the quality of the EEG signal without excessive
      computer power or additional hardware than standard EEG-compatible equipment.

PMID- 22995781
TI  - Copper phytotoxicity in native and agronomical plant species.
AB  - Copper (Cu) is a widespread soil contaminant that is known to be highly toxic to
      soil biota. Limited information is available on the response of wild endemic
      species to Cu in the literature, which hinders ecological risk assessments and
      revegetation. In the present study, the phytotoxicity of Cu in nutrient solution
      was studied in five Australian endemic plant species (Acacia decurrens,
      Austrodanthonia richardsonii (Wallaby Grass), Bothriochloa macra (Redgrass),
      Eucalyptus camaldulensis var. camaldulensis (River Red-Gum) and Dichanthium
      sericeum (Bluegrass) and two vegetable plants species (Lactuca sativa L. 'Great
      lakes' and Raphanus sativa L.). Vegetable species were grown in a more
      concentrated nutrient solution. The response of B. macra was also compared
      between the two nutrient solutions (dilute and concentrated nutrient solution).
      In the first experiment, D. sericeum and E. camaldulensis were found to be highly
      sensitive to Cu exposure in nutrient culture. Critical exogenous Cu
      concentrations (50 percent reduction in roots) for E. camaldulensis, D. sericeum,
      A. richardsonii, B. macra (dilute), L. sativa, B. macra (concentrated), R. sativa
      and A. decurrens were, respectively, (MUg/L) 16, 35, 83, 88, 97, 105, 128 and
      186. Copper tolerance in B. macra was observed to be higher in the more
      concentrated nutrient solution despite the estimated Cu(2+) concentration being
      very similar in treatment solutions. Additional short-term rhizo-accumulation
      studies showed that neither Ca(2+) not K(+) was responsible for reduced uptake at
      the roots. However, the estimated maximum shoot Cu was reduced from 41 to 24mg/kg
      in the more concentrated solution.

PMID- 22995782
TI  - Cytogenetic biomarkers for the assessment of the influence of pollution on
      natural fish populations.
AB  - Cytogenetic analysis methods were used to study the developing embryos of the
      following four Coregonidae species: Coregonus peled (Gmelin), Coregonus lavaretus
      (Gmelin), Coregonus nasus (Pallas) and Coregonus muksun (Pallas). Spawners of
      these species were selected from rivers and lakes of the Tyumen region (Russia)
      with different levels of pollution. The variability of the chromosomal aberration
      rate was analyzed during a monitoring period of more than 20 years. The level of
      chromosomal mutability in the embryonic cells of these fishes was found to have
      steadily increased during the observation period (1989-2011). The higher
      frequency of chromosomal mutations at different stages of embryogenesis in broad
      whitefish, C. nasus (Pallas), was noted in comparison with other species. The
      possible use of chromosomal mutation frequency as an indicator (biomarker) to
      characterize the state of a population is discussed.

PMID- 22995783
TI  - Geochemical and geo-statistical assessment of selected heavy metals in the
      surface sediments of the Gorgan Bay, Iran.
AB  - We investigated heavy metal concentrations of zinc (Zn), copper (Cu), chromium
      (Cr), and lead (Pb), their spatial distribution and enrichment factor index in
      surface sediments of the Gorgan Bay. Sediment Quality Guidelines were also
      applied to assess adverse biological effects of these metals. Heavy metals were
      determined by inductively coupled plasma-mass spectroscopy (ICP-MS). The results
      indicated mean concentrations (ppm) of heavy metals were (mean+/-S.D.) Pb: 11.5+/
      4.88, Cu: 18+/-8.83, Zn: 42+/-22.15 and Cr: 32+/-15.19. Based on Enrichment
      index, the Gorgan Bay is a low-enriched to non-enriched bay. Heavy metal contents
      were lower than the standard limits of PEL, ERL, and ERM that reveal no
      threatening influence of the metals in the Bay.

PMID- 22995784
TI  - Geographical variability of environmental parameters versus GPS precision: toward
      a better sampling strategy.
AB  - To characterize a sedimentary environment, it is risky to take a single sample
      when the spatial variability is unknown. A reference station has to reflect the
      natural variations in order to allow the creation of long time series. However,
      it can remain unclear whether the temporal changes are real or due to a spatial
      variation. We highlight here the importance of spatial variability at the scale
      of precision of the GNSS. It appears that the number and arrangement of
      replicates depend on the environment and the studied parameters. InC, TOC and TS
      show a sufficiently low spatial variability to allow temporal tracking using GNSS
      without multiplying samples. The fine fraction percent shows a high spatial
      variability over small distances. The study of this parameter in the framework of
      temporal tracking requires a knowledge of its spatial variability during each
      period of sampling, and hence leads to the multiplication of samples.

PMID- 22995785
TI  - Plastic consumption and diet of Glaucous-winged Gulls (Larus glaucescens).
AB  - We analyzed dietary habits and presence of plastic in 589 boluses of Glaucous
      winged Gulls (Larus glaucescens) as one of two studies on the impact of plastics
      on marine life in the US Salish Sea. Volunteers dissected boluses collected (2007
      2010) from Protection Island, Washington. Components were separated into 23 food
      and non-food categories. Plastic was found in 12.2% of boluses, with plastic film
      being the most common plastic form. No diet specialization was observed.
      Vegetation was the most abundant component, found in 91.3% of boluses. No
      relationship was observed between any dietary items and occurrence or type of
      plastic found. Load and potential ecological impact in the marine environment can
      be expected to increase concurrently with increasing plastic use and number and
      variety of plastic sources. Future studies are necessary to understand the
      impacts of plastic ingestion on this species.

PMID- 22995786
TI  - The oxidative damage and inflammation caused by pesticides are reverted by lipoic
      acid in rat brain.
AB  - We have previously demonstrated that the administration of low doses of
      dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for
      5weeks) provokes severe oxidative stress (OS) in specific brain regions:
      substantia nigra, cortex and hippocampus. These effects were also observed in
      plasma. Lipoic acid (LA) is considered an "ideal antioxidant" due to its ability
      to scavenge reactive species, reset antioxidant levels and cross the blood-brain
      barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and
      100mg/kg) simultaneously with the pesticide mixture (PM) for 5weeks. After
      suppression of PM administration, we evaluated the restorative effect of LA for a
      further 5weeks. LA prevented OS and the production of nitrites+nitrates [NOx]
      caused by PM in a dose-dependent manner. The PM-induced decrease in reduced
      glutathione and alpha-tocopherol levels in all brain regions was completely
      restored by LA at both high doses. PM administration also caused an increase in
      prostaglandins E(2) and F(2alpha) in brain that was reduced by LA in a dose
      dependent fashion. Taking into account the relationship between OS, inflammation
      and apoptosis, we measured caspase and calpain activity. Only milli- and micro
      calpain isoforms were increased in the PM-treated group and LA reduced the
      activities to basal levels. We also demonstrated that interrupting PM
      administration is not enough to restore the levels of all the parameters measured
      and that LA is necessary to achieve basal status. In our experimental model LA
      displayed a protective role against pesticide-induced damage, suggesting that LA
      administration is a promising therapeutic strategy to cope with disorders
      suspected to be caused by OS generators, especially in brain.

PMID- 22995787
TI  - Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO
      1 induction in retinal ganglion cells.
AB  - Nipradilol (Nip), which has alpha1- and beta-adrenoceptor antagonist and nitric
      oxide (NO)-donating properties, has clinically been used as an anti-glaucomatous
      agent in Japan. NO mediates cellular signaling pathways that regulate
      physiological functions. The major signaling mechanisms mediated by NO are cGMP
      dependent signaling and protein S-nitrosylation-dependent signalings. Nip has
      been described as having neuroprotective effects through cGMP-dependent pathway
      in retinal ganglion cells (RGCs). However, the effect seems to be partial. On the
      other hand, whether Nip can prevent cell death through S-nitrosylation is not yet
      clarified. In this study, we therefore focused on the neuroprotective mechanism
      of Nip through S-nitrosylation. Nip showed a dramatic neuroprotective effect
      against oxidative stress-induced death of RGC-5 cells. However, denitro
      nipradilol, which does not have NO-donating properties, was not protective
      against oxidative stress. Furthermore, an NO scavenger significantly reversed the
      protective action of Nip against oxidative stress. In addition, we demonstrated
      that alpha1- or beta-adrenoceptor antagonists (prazosin or timolol) did not show
      any neuroprotective effect against oxidative stress in RGC-5 cells. We also
      demonstrated that Nip induced the expression of the NO-dependent antioxidant
      enzyme, heme oxygenase-1 (HO-1). S-nitrosylation of Kelch-like ECH-associated
      protein by Nip was shown to contribute to the translocation of NF-E2-related
      factor 2 to the nucleus, and triggered transcriptional activation of HO-1.
      Furthermore, RGC death and levels of 4-hydroxy-2-nonenal (4HNE) were increased
      after optic nerve injury in vivo. Pretreatment with Nip significantly suppressed
      RGC death and accumulation of 4HNE after injury through an HO-1 activity
      dependent mechanism. These data demonstrate a novel neuroprotective action of Nip
      against oxidative stress-induced RGC death in vitro and in vivo.

PMID- 22995788
TI  - Long-term daily access to alcohol alters dopamine-related synthesis and signaling
      proteins in the rat striatum.
AB  - Chronic alcohol exposure can adversely affect neuronal morphology, synaptic
      architecture and associated neuroplasticity. However, the effects of moderate
      levels of long-term alcohol intake on the brain are a matter of debate. The
      current study used 2-DE (two-dimensional gel electrophoresis) proteomics to
      examine proteomic changes in the striatum of male Wistar rats after 8 months of
      continuous access to a standard off-the-shelf beer in their home cages. Alcohol
      intake under group-housed conditions during this time was around 3-4 g/kg/day, a
      level below that known to induce physical dependence in rats. After 8 months of
      access rats were euthanased and 2-DE proteomic analysis of the striatum was
      conducted. A total of 28 striatal proteins were significantly altered in the beer
      drinking rats relative to controls. Strikingly, many of these were dopamine (DA)
      related proteins, including tyrosine hydroxylase (an enzyme of DA biosynthesis),
      pyridoxal phosphate phosphatase (a co-enzyme in DA biosynthesis), DA and cAMP
      regulating phosphoprotein (a regulator of DA receptors and transporters), protein
      phosphatase 1 (a signaling protein) and nitric oxide synthase (which modulates DA
      uptake). Selected protein expression changes were verified using Western
      blotting. We conclude that long-term moderate alcohol consumption is associated
      with substantial alterations in the rat striatal proteome, particularly with
      regard to dopaminergic signaling pathways. This provides potentially important
      evidence of major neuroadaptations in dopamine systems with daily alcohol
      consumption at relatively modest levels.

PMID- 22995789
TI  - Exploring atomic-scale lateral forces in the attractive regime: a case study on
      graphite (0001).
AB  - A non-contact atomic force microscopy-based method has been used to map the
      static lateral forces exerted on an atomically sharp Pt/Ir probe tip by a
      graphite surface. With measurements carried out at low temperatures and in the
      attractive regime, where the atomic sharpness of the tip can be maintained over
      extended time periods, the method allows the quantification and directional
      analysis of lateral forces with piconewton and picometer resolution as a function
      of both the in-plane tip position and the vertical tip-sample distance, without
      limitations due to a finite contact area or to stick-slip-related sudden jumps of
      tip apex atoms. After reviewing the measurement principle, the data obtained in
      this case study are utilized to illustrate the unique insight that the method
      offers. In particular, the local lateral forces that are expected to determine
      frictional resistance in the attractive regime are found to depend linearly on
      the normal force for small tip-sample distances.

PMID- 22995790
TI  - Analysis of the anti-A and anti-B hemagglutinin titers in blood donors from the
      Hospital de Clinicas de Porto Alegre.

PMID- 22995791
TI  - The non-casual relation between eosinophilia and thrombotic microangiopathy.
AB  - There are only a few cases in the literature that describes the association
      between hypereosinophilic syndromes and thrombotic microangiopathy (TMA). Here we
      present the case of a man who suddenly developed a TMA in the context of
      eosinophilic pneumonia, who recovered successfully with six sessions of
      plasmapheresis and corticoids. Although the Pathophysiology is unknown, we
      hypothesize about the prothrombotic effects of the eosinophils. Also we describe
      a literature review.

PMID- 22995798
TI  - From the editor.

PMID- 22995799
TI  - Blood pressure and treatment of persons with hypertension as it relates to
      cognitive outcomes including executive function.

PMID- 22995800
TI  - Nebivolol prevents myocardial fibrosis and diastolic dysfunction in salt-loaded
      spontaneously hypertensive rats.
AB  - BACKGROUND: We have demonstrated previously that a high-salt diet (HS) produces
      myocardial fibrosis, left ventricular (LV) dysfunction, and renal insufficiency
      in adult spontaneously hypertensive rats (SHR), and that blockade of the renin
      angiotensin system prevented those adverse effects of HS. METHODS AND RESULTS:
      Eight-week-old male SHR were divided into four groups: controls received regular
      rat chow (0.6 NaCl); the other three were given HS. The second group was given
      placebo; the third, nebivolol (2 * 10 mg/kg/day) orally; and, the fourth, the
      same dose of nebivolol by osmotic minipump. Rats received respective treatments
      for 8 weeks. The data demonstrated that the HS induced increased cardiac mass
      (2.85 +/- 0.05 vs. 5.36 +/- 0.22 mg/g; P < .05 in control and HS groups,
      respectively); LV fibrosis as indicated by higher hydroxyproline concentration;
      further increase in arterial pressure (161 +/- 7 vs. 184 +/- 8 mm Hg; P < .05);
      myocardial ischemia; and LV diastolic dysfunction. Nebivolol ameliorated the
      adverse cardiac effects of HS, demonstrated by decreased LV mass and fibrosis and
      improved coronary hemodynamics and LV function. CONCLUSIONS: The effects of
      nebivolol were independent of arterial pressure. The results of this study
      provide important laboratory data that support a rationale for nebivolol in the
      treatment of patients with hypertension having diastolic dysfunction with
      preserved ejection fraction.

PMID- 22995801
TI  - Bone marrow transplantation improves endothelial function in hypertensive Dahl
      salt-sensitive rats.
AB  - Bone marrow-derived endothelial progenitor cells (EPCs) constitute an important
      endogenous system in the maintenance of endothelial integrity and vascular
      homeostasis. Cardiovascular risk factors are associated with a reduced number and
      functional capacity of EPCs. Here we investigated the effect of transplantation
      of bone marrow-derived cells from Dahl salt-resistant rat into age-matched Dahl
      salt-sensitive (DS) rat on blood pressure, endothelial function, and circulating
      EPC number. The recipient DS rats were fed a normal (0.5% NaCl, NS) or high-salt
      (4% NaCl, HS) diet for 6 weeks after bone marrow transplantation (BMT). DS rats
      on a NS or a HS diet without BMT were used as controls. Hypertensive DS (HS-DS)
      rat (systolic blood pressure: 213 +/- 4 mm Hg vs. 152 +/- 4 mm Hg in NS, P < .05)
      manifested impaired endothelium-dependent relaxation to acetylcholine (EDR),
      increased gene expression of vascular oxidative stress and proinflamamtory
      cytokines, and decreased eNOS expression. BMT on HS-DS rat significantly improved
      EDR and eNOS expression, reduced oxidative stress without reduction in SBP (206
      +/- 6 mm Hg). Flow cytometry analysis showed that there was no difference in the
      number of circulating EPCs, demonstrated by expression of EPC markers CD34, cKit,
      and vascular endothelial growth factor, between hypertensive and normotensive
      rats. Surprisingly, BMT resulted in a 5- to 10-fold increase in the previously
      mentioned EPC markers in hypertensive, but not normotensive rat. These results
      suggest that DS rat has an impaired ability to increase bone marrow-derived EPCs
      in response to HS diet challenge, which may contribute to endothelial
      dysfunction.

PMID- 22995802
TI  - Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren
      + valsartan) therapy.
AB  - Aldosterone levels increase in 30%-40% of patients on angiotensin-converting
      enzyme inhibitors and/or angiotensin receptor blockers over the long term. This
      "aldosterone breakthrough" may carry important clinical consequences given
      aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor,
      aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS)
      proximally, may limit breakthrough compared to conventional RAAS blockade. This
      open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A),
      valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V)
      for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular
      filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP)
      >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to
      24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9
      months. Aldosterone breakthrough was defined as a sustained increase from
      baseline aldosterone by study end. The study was intended to enroll 120 subjects
      but was terminated early by the sponsor. We present here the results of 33
      subjects who completed the protocol, of which 12 were randomized to A, 11 were
      randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (+/
      23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (+/-2943) mg/day; and
      baseline BP was 134.7 (+/-10.5)/84.8 (+/-8.4) mm Hg. Three (27%) subjects on V,
      three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone
      breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects:
      30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean
      BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with
      breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren,
      alone or in combination with valsartan, did not reduce the incidence of
      aldosterone breakthrough in subjects with hypertension and proteinuria compared
      with conventional RAAS blockade.

PMID- 22995803
TI  - Active ambulatory care management supported by short message services and mobile
      phone technology in patients with arterial hypertension.
AB  - The use of short message services and mobile phone technology for ambulatory care
      management is the most accessible and most inexpensive way to transition from
      traditional ambulatory care management to active ambulatory care management in
      patients with arterial hypertension (AH). The aim of this study was to compare
      the clinical efficacy of active ambulatory care management supported by short
      message services and mobile phone technology with traditional ambulatory care
      management in AH patients. The study included 97 hypertensive patients under
      active ambulatory care management and 102 patients under traditional ambulatory
      care management. Blood pressure levels, body mass, and smoking history of
      patients were analyzed in the study. The duration of study was 1 year. In the
      active ambulatory care management group, 36% of patients were withdrawn from the
      study within a year. At the end of the year, 77% of patients from the active care
      management group had achieved the goal blood pressure level. That was more than 5
      times higher than that in the traditional ambulatory care management group (P <
      .001). The risk ratio of achieving and maintaining the goal blood pressure in
      patients of active care management group was 5.44, CI (3.2-9.9; P = .005).
      Implementation of active ambulatory care management supported by short message
      services and mobile phone improves the quality of ambulatory care of hypertensive
      patients.

PMID- 22995804
TI  - Association between obesity and the severity of ambulatory hypertension in
      children and adolescents.
AB  - The goal of our study was to analyze the association between obesity and the
      severity of ambulatory hypertension in obese children. A total of 109 patients
      with primary obesity ages 7 to 18 years (mean +/- SD age 14.1 +/- 3.1) were
      enrolled. Patients were divided into three groups according to body mass index
      (BMI) Z-scores: group 1 (n = 27): BMI >1.65 and < 3.28 standard deviation scores
      (SDS); group 2 (n = 55): BMI >3.29 and <4.91 SDS; group 3 (n = 27): BMI >4.92
      SDS. Definition and staging of ambulatory hypertension was based on blood
      pressure (BP) levels and BP load, obtained from ambulatory BP monitoring (ABPM).
      Only 24% had ambulatory normotension, 25% had ambulatory prehypertension, 3% had
      hypertension, and 48% had severe ambulatory hypertension. The severity of
      hypertension increased significantly with the degree of obesity (P = .0027).
      Daytime systolic, diastolic, and mean arterial BPs increased significantly with
      increased BMI, whereas the nighttime pressure remained elevated regardless of the
      degree of obesity. Isolated nighttime hypertension was observed in 25% of
      patients and 38% were classified as nondippers. Almost 50% of children with
      obesity and hypertension detected on ABPM suffer from severe ambulatory
      hypertension. BMI is associated with the severity of ambulatory hypertension and
      the increase of daytime BP.

PMID- 22995805
TI  - Construction of life-course occupational trajectories: evidence for work as a
      mediator of racial disparities in hypertension.
AB  - OBJECTIVE: To determine whether a life-course model of work may explain racial or
      ethnic differentials in health. Occupational characteristics are relevant
      socioeconomic indicators of health disparities and essential determinants of
      health. METHODS: Growth mixture modeling (GMM) was used to construct longitudinal
      trajectories of work characteristics from the ages of 20 to 32 years. Path
      analyses were used to evaluate the association of race, ethnicity, education, and
      work trajectory on incident hypertension. RESULTS: Growth mixture modeling
      yielded three latent class trajectories. Black subjects with postsecondary
      education were 2.5 times more likely to be found in the lowest occupational
      trajectory. The three-class trajectory model mediated 43.6% of the direct effect
      of race on incident hypertension. CONCLUSIONS: Latent class trajectories of work
      demonstrated a stronger association with incident hypertension than did measures
      of current work, and clearly mediated the effects of race on hypertension.

PMID- 22995806
TI  - Longitudinal spirometry among patients in a treatment program for community
      members with World Trade Center-related illness.
AB  - OBJECTIVE: The course of lung function in community members exposed to World
      Trade Center (WTC) dust and fumes remains undefined. We studied longitudinal
      spirometry among patients in the WTC Environmental Health Center (WTCEHC)
      treatment program. METHODS: Observational study of 946 WTCEHC patients with
      repeated spirometry measures analyzed on the population as a whole and stratified
      by smoking status, initial spirometry pattern, and WTC-related exposure category.
      RESULTS: Improvement in forced vital capacity (54.4 mL/yr; 95% confidence
      interval, 45.0 to 63.8) and forced expiratory volume in 1 second (36.8 mL/yr; 95%
      confidence interval, 29.3 to 44.3) was noted for the population as a whole. Heavy
      smokers did not improve. Spirometry changes differed depending on initial
      spirometry pattern and exposure category. CONCLUSION: These data demonstrate
      spirometry improvement in select populations suggesting reversibility in airway
      injury and reinforcing the importance of continued treatment.

PMID- 22995808
TI  - Using the work limitations questionnaire in patients with a chronic condition in
      the Netherlands.
AB  - OBJECTIVE: To examine the intelligibility and psychometric properties of the
      modified Dutch language version of the Work Limitations Questionnaire (WLQ) (WLQ
      mdlv). METHODS: Employed patients with a physical chronic condition completed the
      WLQ-mdlv, the Work Ability Index, and the 36-item short form health survey.
      Intelligibility, internal consistency, test-retest reliability, and external
      construct validity of the WLQ-mdlv were assessed. RESULTS: In 125 patients, the
      WLQ-mdlv showed improved intelligibility for a Dutch population. With Cronbach
      alpha coefficients more than .80, squared weighted kappa of 0.63 or more
      (individual items), intraclass correlation coefficients of 0.83 or more (WLQ
      scales), a minimal detectable change of four points (WLQ index), and negative
      correlations with the Work Ability Index and related 36-item short form health
      survey scales reliability and external construct validity of the WLQ-mdlv were
      confirmed. CONCLUSION: The WLQ-mdlv is an intelligible, reliable, and valid
      instrument for evaluating work limitations in employees with a chronic condition
      in the Netherlands.

PMID- 22995809
TI  - Impact of weight gain on cardiovascular risk factors in Japanese male workers.
AB  - OBJECTIVE: To evaluate the impact of weight gain on cardiovascular risk factors
      among younger (25 to 44 years) and older (45 to 64 years) Japanese male workers
      in terms of population attributable risk percentage (PAR%). METHODS: Using the
      2008 and 2009 health examination data, 49,587 eligible male workers aged 25 to 64
      years were examined for their 1-year changes in body weight and cardiovascular
      risk factors. RESULTS: Mean weight change was significantly greater than zero in
      the younger group (+0.27 kg) but not in the older group (-0.08 kg). The PAR% due
      to weight gain for the development and maintenance of cardiovascular risk factors
      was estimated at 21.8% and 5.4%, respectively, in the younger and older groups.
      CONCLUSIONS: The age-stratified PAR% estimates suggest that weight gain
      prevention programs will make greater contributions to cardiovascular health in
      younger than in older male workers.

PMID- 22995810
TI  - Screening for sleep disordered breathing among applicants for a professional
      driver's license.
AB  - OBJECTIVES: Individuals with sleep disordered breathing (SDB) are at high risk
      for falling asleep while driving. The aim of this study was to identify variables
      that would predict SDB among healthy young applicants for a professional driver's
      license. METHOD: A total of 301 applicants for a driver's license completed self
      administered questionnaires. Sleep was recorded for one night with the Watch
      peripheral arterial tone-100. To identify possible predictors of SDB (Respiratory
      Disturbance Index >15), we employed new statistical methods. RESULTS: The
      following items were identified as significant predictors of SDB: body mass
      index, age, Mini Sleep Questionnaire, smoking, father snoring, afternoon nap
      taking, and falling asleep while traveling as a passenger. Moderate or severe SDB
      was prevalent in at least 25% of the applicants. CONCLUSION: New statistical
      methods revealed that a combination of questions related to sleep habits,
      complaints, and demographic data predicted most of the clinically significant
      SDB.

PMID- 22995811
TI  - Employment contracts and health selection: unhealthy employees out and healthy
      employees in?
AB  - OBJECTIVE: The healthy worker effect implies that healthy workers go "up" in
      employment status whereas less healthy workers go "down" into precarious
      temporary employment or unemployment. These hypotheses were tested during an
      economic recession, by predicting various upward and downward contract
      trajectories, based on workers' health status, work-related well-being, and work
      ability. METHODS: Two waves (2008 and 2009) of the Netherlands Working Conditions
      Cohort Study (N = 7112) were used and logistic regression analyses were performed
      to test the hypothesis of this study. RESULTS: Lower general health and higher
      emotional exhaustion at baseline predicted future unemployment among permanent
      employees. Various downward trajectories were also predicted by lower work
      related well-being and lower work ability, whereas the opposite was true for one
      of the upward trajectories. CONCLUSIONS: Workers with lower health, lower work
      related well-being, or lower work ability are at risk for ending up in precarious
      temporary employment or unemployment.

PMID- 22995812
TI  - A road map toward a globally harmonized approach for occupational health
      surveillance and epidemiology in nanomaterial workers.
AB  - OBJECTIVE: Few epidemiological studies have addressed the health of workers
      exposed to novel manufactured nanomaterials. The small current workforce will
      necessitate pooling international cohorts. METHOD: A road map was defined for a
      globally harmonized framework for the careful choice of materials, exposure
      characterization, identification of study populations, definition of health
      endpoints, evaluation of appropriateness of study designs, data collection and
      analysis, and interpretation of the results. RESULTS: We propose a road map to
      reach global consensus on these issues. The proposed strategy should ensure that
      the costs of action are not disproportionate to the potential benefits and that
      the approach is pragmatic and practical. CONCLUSIONS: We should aim to go beyond
      the collection of health complaints, illness statistics, or even counts of
      deaths; the manifestation of such clear endpoints would indicate a failure of
      preventive measures.

PMID- 22995813
TI  - Efficacy of a "small-changes" workplace weight loss initiative on weight and
      productivity outcomes.
AB  - OBJECTIVE: The effect of weight reduction on workplace productivity is unknown.
      We have investigated a "small-changes" workplace weight loss intervention on
      weight and productivity outcomes. METHODS: Overweight/obese employees at two New
      Zealand worksites (n = 102) received the 12-week intervention. One site received
      an extra 9-month weight-maintenance component. Magnitudes of effects on weight
      and productivity were assessed via standardization. RESULTS: Both groups reduced
      weight at 12 weeks and maintained lost weight at 12 months. There were small
      possible improvements in productivity at one worksite and trivial reductions at
      the other by 12 weeks, with little subsequent change during maintenance in either
      group. At an individual level, weight change was associated with at most only
      small improvements or small reductions in productivity. CONCLUSION: Workplace
      weight loss initiatives may need to be more intensive or multidimensional to
      enhance productivity.

PMID- 22995814
TI  - A "small-changes" workplace weight loss and maintenance program: examination of
      weight and health outcomes.
AB  - OBJECTIVE: To compare the effect of "small-changes" and "usual care" workplace
      interventions on weight loss and to investigate the effect of small changes with
      or without maintenance on weight and health outcomes. METHODS: Overweight/obese
      employees at two New Zealand worksites received a 12-month usual-care
      intervention (n = 53), followed by a 12-month small-changes intervention (n =
      102). Small changes comprised a 12-week component, followed by 9 months of
      maintenance, implemented at only one worksite. Magnitudes of effects were
      assessed via a threshold of -5% (weight loss) and standardization (health
      outcomes). RESULTS: Small changes showed beneficial weight loss relative to usual
      care in both worksites. For small-changes interventions, worksites reduced weight
      (12 weeks) and maintained lost weight (12 months). One in every three
      participants lost 5% or more weight. Some improvements in health outcomes were
      shown. CONCLUSION: Regardless of maintenance, the small-changes intervention was
      successful in sustaining weight loss.

PMID- 22995815
TI  - Work absences and expenditures for employees with autoimmune inflammatory
      diseases.
AB  - OBJECTIVE: Economic burden was compared for employees with autoimmune
      inflammatory diseases (AutoIDs) who received anti-tumor necrosis factor (TNF)
      alpha agents, those who did not, and those with no AutoID. METHODS: Retrospective
      claims data analysis (2000-2006). Propensity analysis created two groups: (1)
      adult AutoID patients with anti-TNFalpha therapy (AutoID/anti-TNFalpha) matched
      to those with no anti-TNFalpha therapy (AutoID/non-anti-TNFalpha), and (2) non
      AutoID patients (control) matched to all AutoID patients (AutoID). Indirect,
      direct, and total expenditures after controlling for various covariates were
      compared using regression analysis. RESULTS: Total direct and total expenditures
      were, respectively, $13,187 and $13,373 higher for AutoID/anti-TNFalpha group (n
      = 689) versus AutoID/non-anti-TNFalpha group (n = 2699). Indirect expenditures
      were not statistically different between the groups. AutoID- (n = 12,612) and
      control-group (n = 48,895) differences showed similar trends. CONCLUSIONS: These
      results provide useful information to employers about the cost burden associated
      with AutoIDs.

PMID- 22995816
TI  - Residential pesticide use is associated with children's respiratory symptoms.
AB  - OBJECTIVE: To characterize the association between residential pesticide
      application and acute and chronic respiratory symptoms in children, focusing on
      the location of the pesticide application in and around the home and the type of
      pesticide applicator (professional vs nonprofessional). METHODS: We used 1999 to
      2004 National Health and Nutrition Examination Survey results to investigate this
      association in children younger than 18 years (N = 14,065). RESULTS: Overall,
      pesticide use in the home was not associated with wheezing (odds ratio [OR],
      1.15; 95% confidence interval [CI], 0.91 to 1.47). Nevertheless, pesticide use in
      the kitchen or dining rooms was significantly associated with increased odds of
      wheezing (OR, 1.39; 95% CI, 1.08 to 1.78) and dry cough (OR, 2.38; 95% CI, 1.40
      to 4.06) after controlling for covariates. CONCLUSIONS: These findings suggest
      that residential use of pesticides and the location of pesticide application are
      associated with increased respiratory complaints in children.

PMID- 22995807
TI  - Development of the Huntington disease work function scale.
AB  - OBJECTIVE: A work function measure specific for persons with prodromal Huntington
      disease (HD) was created to assist with workplace accommodations. METHODS: A self
      report HD Work Function (HDWF) measure was developed from focus group and expert
      validation. RESULTS: Pilot studies with 238 people with prodromal HD, and 185
      companions; and 89 people without prodromal HD, and 70 companions indicate that
      HDWF has acceptable internal consistency (Cronbach alpha = 0.77), acceptable
      interrater reliability (r = 0.58), and acceptable convergent validity with
      selected items from the Endicott Work Productivity Scale (r = -0.56), Social
      Adjustment Scale-Self Report (r = -0.29), and Everyday Cognition (r = -0.70). The
      HDWF can distinguish between people with prodromal HD and people with an HD
      family history who do not have prodromal HD (P < 0.0001). CONCLUSIONS: The HDWF
      is a brief self-assessment that may be used to monitor work function.

PMID- 22995817
TI  - Aortic dilatation in bicuspid aortic valve disease.

PMID- 22995818
TI  - Tormentic acid derivatives: synthesis and apoptotic activity.
AB  - Several derivatives of tormentic acid have been prepared and tested for their
      antitumor activity. The dichloroacetate 14 is an excellent antitumor active agent
      acting by an apoptose inducing pathway as demonstrated by OA/PI staining, DNA
      laddering experiments as well as by an annexin V binding assay.

PMID- 22995819
TI  - Synthesis and evaluation of novel anti-proliferative pyrroloazepinone and
      indoloazepinone oximes derived from the marine natural product hymenialdisine.
AB  - The tetrahydroazepinone pharmacophore is a component of many interesting
      compounds, including several marine natural products, with anti-cancer
      properties. The synthesis and biological evaluation of a novel series of
      pyrroloazepinone and indoloazepinone oximes is reported. These compounds showed
      promising growth inhibition activity against four human cancer cell lines but did
      not significantly inhibit the cell cycle regulator cyclin dependent kinase 2. The
      most active compounds in this series displayed improved anti-proliferative
      activity over the related synthetic indoloazepine kenpaullone. The structure
      activity relationships exhibited by the azepinone pharmacophore suggests several
      novel lead compounds for anti-cancer drug discovery.

PMID- 22995820
TI  - Prey density, value, and spatial distribution affect the efficiency of area
      concentrated search.
AB  - Searching individuals need to take decisions on where and how long to search.
      When food is spatially aggregated, detection of a food item signals a probability
      for the presence of further prey items in its surrounding. Organisms can thus
      intensify search effort upon detecting a prey item, but after unsuccessfully
      searching for a while, return to the previous, extensive search, this strategy is
      known as 'area-concentrated-search' (ACS). Here we present results of simulations
      where individuals perform ACS employing a correlated random walk with variable
      directional persistence. Switching between intensive and extensive search (with
      respectively low and high directional persistence) is a function of searcher's
      internal state represented as 'satiety' level depending on preceding consumption
      of prey items. We explore the effect of this function's control parameters
      ('switching level' i.e., the satiety at which the switching occurs, and the
      switchover shape parameter) on searching efficiency in dependence of (1) prey
      items' spatial distribution ranging from randomly uniform to highly contagious,
      (2) the overall prey density, and (3) prey 'caloric' value. Our main conclusions:
      (1) the form of the adopted switchover exerts an effect on searching efficiency,
      and this effect is most pronounced in landscapes with highly aggregated
      resources. Except for the most homogeneous prey distributions, there was a clear
      optimum area within the movement parameter space, yielding highest efficiency.
      (2) The optimal switching level is larger in heterogeneous landscapes, but
      optimum switchover shape is little affected by any of the landscape attributes.
      In most landscapes, it is most profitable to switch gradually rather than
      abruptly. (3) The success and optimal switching level depend not only on the
      prey's spatial distribution but also on average prey density while the value of
      prey items has little effect on the optimal movement parameters.

PMID- 22995821
TI  - Overlapping genes coded in the 3'-to-5'-direction in mitochondrial genes and 3'
      to-5' polymerization of non-complementary RNA by an 'invertase'.
AB  - Suppressor tRNAs induce expression of additional (off-frame) genes coded by
      stopless genetic codes without lengthening genomes, decreasing DNA replication
      costs. RNA 3'-to-5' polymerization by tRNAHis guanylyltransferase suggests
      further cryptic code: hypothetical 'invertases' polymerizing in the 3'-to-5'
      direction, advancing in the 5'-to-3' direction would produce non-complementary
      RNA templated by regular genes, with different coding properties. Assuming
      'invertase' activity, BLAST analyses detect GenBank-stored RNA ESTs and proteins
      (some potentially coding for the hypothesized invertase) for human mitochondrial
      genes. These peptides' predicted secondary structures resemble their GenBank
      homologues'. 3'-to-5' EST lengths increase with their self-hybridization
      potential: Single-stranded RNA degradation perhaps limits 3'-to-5' elongation.
      Independent methods confirm predicted 3'-to-5' overlapping genes: (a) Presumed 3'
      to-5' overlapping genes avoid codons belonging to circular codes; (b) Spontaneous
      replicational deamination (mutation) gradients occur at 3rd codon positions,
      unless these are involved in overlap coding, because mutations are counter
      selected in overlapping genes. Tests a and b converge on predicted 3'-to-5' gene
      expression levels. Highly expressed ones include also fewer stops, and
      mitochondrial genomes (in Primates and Drosophila) adapt to avoid dependence of
      3'-to-5' coding upon antitermination tRNA activity. Secondary structure, circular
      code, gradient and coevolution analyses yield each clear positive results
      independently confirming each other. These positive results (including physical
      evidence for 3'-to-5' ESTs) indicate that 3'-to-5' coding and invertase activity
      is an a priori improbable working hypothesis that cannot be dismissed. Note that
      RNAs produced by invertases potentially produce triple-stranded DNA:RNA helices
      by antiparallel Hoogsteen pairings at physiological pH, as previously observed
      for mitochondrial genomes.

PMID- 22995822
TI  - Mathematical model of cycad cones' thermogenic temperature responses: inverse
      calorimetry to estimate metabolic heating rates.
AB  - A mathematical model based on conservation of energy has been developed and used
      to simulate the temperature responses of cones of the Australian cycads
      Macrozamia lucida and Macrozamia. macleayi during their daily thermogenic cycle.
      These cones generate diel midday thermogenic temperature increases as large as 12
      degrees C above ambient during their approximately two week pollination period.
      The cone temperature response model is shown to accurately predict the cones'
      temperatures over multiple days as based on simulations of experimental results
      from 28 thermogenic events from 3 different cones, each simulated for either 9 or
      10 sequential days. The verified model is then used as the foundation of a new,
      parameter estimation based technique (termed inverse calorimetry) that estimates
      the cones' daily metabolic heating rates from temperature measurements alone. The
      inverse calorimetry technique's predictions of the major features of the cones'
      thermogenic metabolism compare favorably with the estimates from conventional
      respirometry (indirect calorimetry). Because the new technique uses only
      temperature measurements, and does not require measurements of oxygen
      consumption, it provides a simple, inexpensive and portable complement to
      conventional respirometry for estimating metabolic heating rates. It thus
      provides an additional tool to facilitate field and laboratory investigations of
      the bio-physics of thermogenic plants.

PMID- 22995823
TI  - In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium
      channel: implications for amyotrophic lateral sclerosis therapy.
AB  - Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder
      characterized mainly by a progressive loss of motor neurons. Glutamate
      excitotoxicity is likely the main cause of neuronal death, and Riluzole
      interferes with glutamate-mediated transmission. Thus, in such independent
      pathway, these effects may be partly due to inactivation of voltage-dependent
      sodium channels. Here we predict the structural model of the interaction and
      report the possible binding sites of Riluzole on Nav1.6 channel. The docked
      complexes were subjected to minimization and we further investigated the key
      interacting residues, binding free energies, pairing bridge determination,
      folding pattern, hydrogen bounding formation, hydrophobic contacts and
      flexibilities. Our results demonstrate that Riluzole interacts with the Nav1.6
      channel, more specifically in the key residues TYR 1787, LEU 1843 and GLN 1799,
      suggesting possible cellular implications driven by these amino acids on Riluzole
      Nav1.6 interaction, which may serve as an important output for a more specific
      and experimental drug design therapy against ALS.

PMID- 22995824
TI  - Ensuring continuous high-quality care for people with impaired cognition
      including dementia at the end of life.

PMID- 22995825
TI  - Simplifying the review of thromboprophylaxis decisions in a palliative care
      inpatient unit.

PMID- 22995826
TI  - The establishment and initial outcomes of a palliative care bereavement service.

PMID- 22995827
TI  - Toward a molecular understanding of RNA remodeling by DEAD-box proteins.
AB  - DEAD-box proteins are superfamily 2 helicases that function in all aspects of RNA
      metabolism. They employ ATP binding and hydrolysis to generate tight, yet
      regulated RNA binding, which is used to unwind short RNA helices non-processively
      and promote structural transitions of RNA and RNA-protein substrates. In the last
      few years, substantial progress has been made toward a detailed, quantitative
      understanding of the structural and biochemical properties of DEAD-box proteins.
      Concurrently, progress has been made toward a physical understanding of the RNA
      rearrangements and folding steps that are accelerated by DEAD-box proteins in
      model systems. Here, we review the recent progress on both of these fronts,
      focusing on the mitochondrial DEAD-box proteins Mss116 and CYT-19 and their
      mechanisms in promoting the splicing of group I and group II introns.

PMID- 22995828
TI  - Ski2-like RNA helicase structures: common themes and complex assemblies.
AB  - Ski2-like RNA helicases are large multidomain proteins involved in a variety of
      RNA processing and degradation events. Recent structures of Mtr4, Ski2 and Brr2
      provide our first view of these intricate helicases. Here we review these
      structures, which reveal a conserved ring-like architecture that extends beyond
      the canonical RecA domains to include a winged helix and ratchet domain.
      Comparison of apo- and RNA-bound Mtr4 structures suggests a role for the winged
      helix domain as a molecular hub that coordinates RNA interacting events
      throughout the helicase. Unique accessory domains provide expanded diversity and
      functionality to each Ski2-like family member. A common theme is the integration
      of Ski2-like RNA helicases into larger protein assemblies. We describe the
      central role of Mtr4 and Ski2 in formation of complexes that activate RNA decay
      by the eukaryotic exosome. The current structures provide clues into what
      promises to be a fascinating view of these dynamic assemblies.

PMID- 22995830
TI  - The 70S ribosome modulates the ATPase activity of Escherichia coli YchF.
AB  - YchF is one of two universally conserved GTPases with unknown cellular function.
      As a first step toward elucidating YchF's cellular role, we performed a detailed
      biochemical characterization of the protein from Escherichia coli. Our data from
      fluorescence titrations not only confirmed the surprising finding that YchFE.coli
      binds adenine nucleotides more efficiently than guanine nucleotides, but also
      provides the first evidence suggesting that YchF assumes two distinct
      conformational states (ATP- and ADP-bound) consistent with the functional cycle
      of a typical GTPase. Based on an in vivo pull-down experiment using a His-tagged
      variant of YchF from E. coli (YchFE.coli), we were able to isolate a megadalton
      complex containing the 70S ribosome. Based on this finding, we report the
      successful reconstitution of a YchF*70S complex in vitro, revealing an affinity
      (KD) of the YchFE.coli*ADPNP complex for 70S ribosomes of 3 MUM. The in vitro
      reconstitution data also suggests that the identity of the nucleotide-bound state
      of YchF (ADP or ATP) modulates its affinity for 70S ribosomes. A detailed
      Michaelis-Menten analysis of YchF's catalytic activity in the presence and the
      absence of the 70S ribosome and its subunits revealed for the first time that the
      70S ribosome is able to stimulate YchF's ATPase activity (~10-fold), confirming
      the ribosome as part of the functional cycle of YchF. Our findings taken together
      with previously reported data for the human homolog of YchF (hOLA1) indicate a
      high level of evolutionary conservation in the enzymatic properties of YchF and
      suggest that the ribosome is the main functional partner of YchF not only in
      bacteria.

PMID- 22995829
TI  - The DEAD-box helicase eIF4A: paradigm or the odd one out?
AB  - DEAD-box helicases catalyze the ATP-dependent unwinding of RNA duplexes. They
      share a helicase core formed by two RecA-like domains that carries a set of
      conserved motifs contributing to ATP binding and hydrolysis, RNA binding and
      duplex unwinding. The translation initiation factor eIF4A is the founding member
      of the DEAD-box protein family, and one of the few examples of DEAD-box proteins
      that consist of a helicase core only. It is an RNA-stimulated ATPase and a non
      processive helicase that unwinds short RNA duplexes. In the catalytic cycle, a
      series of conformational changes couples the nucleotide cycle to RNA unwinding.
      eIF4A has been considered a paradigm for DEAD-box proteins, and studies of its
      function have revealed the governing principles underlying the DEAD-box helicase
      mechanism. However, as an isolated helicase core, eIF4A is rather the exception,
      not the rule. Most helicase modules in other DEAD-box proteins are modified, some
      by insertions into the RecA-like domains, and the majority by N- and C-terminal
      appendages. While the basic catalytic function resides within the helicase core,
      its modulation by insertions, additional domains or a network of interaction
      partners generates the diversity of DEAD-box protein functions in the cell. This
      review summarizes the current knowledge on eIF4A and its regulation, and
      discusses to what extent eIF4A serves as a model DEAD-box protein.

PMID- 22995831
TI  - Specific temperature-induced perturbations of secondary mRNA structures are
      associated with the cold-adapted temperature-sensitive phenotype of influenza A
      virus.
AB  - For decades, cold-adapted, temperature-sensitive (ca/ts) strains of influenza A
      virus have been used as live attenuated vaccines. Due to their great public
      health importance it is crucial to understand the molecular mechanism(s) of cold
      adaptation and temperature sensitivity that are currently unknown. For instance,
      secondary RNA structures play important roles in influenza biology. Thus, we
      hypothesized that a relatively minor change in temperature (32-39 degrees C) can
      lead to perturbations in influenza RNA structures and, that these structural
      perturbations may be different for mRNAs of the wild type (wt) and ca/ts strains.
      To test this hypothesis, we developed a novel in silico method that enables
      assessing whether two related RNA molecules would undergo (dis)similar structural
      perturbations upon temperature change. The proposed method allows identifying
      those areas within an RNA chain where dissimilarities of RNA secondary structures
      at two different temperatures are particularly pronounced, without knowing
      particular RNA shapes at either temperature. We identified such areas in the NS2,
      PA, PB2 and NP mRNAs. However, these areas are not identical for the wt and ca/ts
      mutants. Differences in temperature-induced structural changes of wt and ca/ts
      mRNA structures may constitute a yet unappreciated molecular mechanism of the
      cold adaptation/temperature sensitivity phenomena.

PMID- 22995832
TI  - Tuning the engine: an introduction to resources on post-transcriptional
      regulation of gene expression.
AB  - In the last years post-transcriptional regulation (PTR) of gene expression has
      been increasingly recognized to be a powerful and general determinant of the
      quantitative changes in proteomes, and therefore a driving force for cell
      phenotypes. By means of networks of trans-factors on one hand, and cis-elements
      found primarily in untranslated regions (UTRs) of mRNA on the other hand, mRNA
      availability to translation and translation rates are tightly controlled and can
      be rapidly tuned according to the changing state of the cell. A number of
      dedicated resources and tools, including databases and predictive algorithms,
      have been proposed as bioinformatics aids for the study of this fundamental layer
      of gene expression regulation. Their use, however, is rendered difficult by
      heterogeneity and fragmentation. This review aims to locate these resources in
      their proper space, classifying them according to their goals, limitations and
      integration capabilities and, in the end, to provide the user with an initial
      toolbox for the bioinformatic analysis of post-transcriptional regulation of gene
      expression. The accompanying website, available at www.ptrguide.org, lists all
      resources, provides summary and features for each one and will be regularly
      updated in the future.

PMID- 22995833
TI  - Mechanisms that impact microRNA stability in plants.
AB  - microRNAs (miRNAs) are 20-24 nucleotide RNAs that regulate a variety of
      developmental and metabolic processes. The accumulation of miRNAs in vivo can be
      controlled at multiple levels. In addition to miRNA biogenesis, mechanisms that
      lead to RNA degradation, such as 3' uridylation and 3' truncation, also affect
      the steady-state levels of miRNAs. On the other hand, 2'-O-methylation in plant
      miRNAs protects their 3' ends from truncation and uridylation. The recent
      identification of HESO1 as the key enzyme responsible for miRNA uridylation in
      Arabidopsis was a first step toward a full understanding of the mechanisms
      underlying miRNA turnover. Analyses of the heso1 mutant predicted the existence
      of another uridylation activity and a previously unknown nuclease that act on
      miRNAs. The future identification of these enzymes will enrich our understanding
      of miRNA turnover.

PMID- 22995834
TI  - Dose-dependent differential mRNA target selection and regulation by let-7a-7f and
      miR-17-92 cluster microRNAs.
AB  - MicroRNAs (miRNAs) are important players of post-transcriptional gene regulation.
      Individual miRNAs can target multiple mRNAs and a single mRNA can be targeted by
      many miRNAs. We hypothesized that miRNAs select and regulate their targets based
      on their own expression levels, those of their target mRNAs and triggered
      feedback loops. We studied the effects of varying concentrations of let-7a-7f and
      the miR-17-92 cluster plasmids on the reporter genes carrying either DICER- or
      cMYC -3'UTR in Huh-7 cells. We showed that let-7 significantly downregulated
      expression of DICER 3'UTR reporter at lower concentrations, but selectively
      downregulated expression of a cMYC 3'UTR reporter at higher dose. This miRNA dose
      dependent target selection was also confirmed in other target genes, including
      CCND1, CDKN1 and E2F1. After overexpressing let-7a-7f or the miR-17-92 clusters
      at wide-ranging doses, the target genes displayed a nonlinear correlation to the
      transfected miRNA. Further, by comparing the expression levels of let-7a and miR
      17-5p, along with their selected target genes in 3 different cell lines, we found
      that the knockdown dose of each miRNA was directly related to their baseline
      expression level, that of the target gene and feedback loops. These findings were
      supported by gene modulation studies using endogenous levels of miR-29, -1 and 
      206 and a luciferase reporter system in multiple cell lines. Finally, we
      determined that the miR-17-92 cluster affected cell viability in a dose-dependent
      manner. In conclusion, we have shown that miRNAs potentially select their targets
      in a dose-dependent and nonlinear fashion that affects biological function; and
      this represents a novel mechanism by which miRNAs orchestrate the finely tuned
      balance of cell function.

PMID- 22995835
TI  - Secondary RNA structure and nucleotide specificity contribute to internal
      initiation mediated by the human tau 5' leader.
AB  - Mechanisms by which eukaryotic internal ribosomal entry sites (IRESs) initiate
      translation have not been well described. Viral IRESs utilize a combination of
      secondary/tertiary structure concomitant with sequence specific elements to
      initiate translation. Eukaryotic IRESs are proposed to utilize the same
      components, although it appears that short sequence specific elements are more
      common. In this report we perform an extensive analysis of the IRES in the human
      tau mRNA. We demonstrate that the tau IRES exhibits characteristics similar to
      viral IRESs. It contains two main structural domains that exhibit secondary
      interactions, which are essential for internal initiation. Moreover, the tau IRES
      is extremely sensitive to small nucleotide substitutions. Our data also indicates
      that the 40S ribosome is recruited to the middle of the IRES, but whether it
      scans to the initiation codon in a linear fashion is questioned. Overall, these
      results identify structural and sequence elements critical for tau IRES activity
      and consequently, provide a novel target to regulate tau protein expression in
      disease states including Alzheimer disease and other tauopathies.

PMID- 22995836
TI  - The human tRNA m (5) C methyltransferase Misu is multisite-specific.
AB  - The human tRNA m ( 5) C methyltransferase Misu is a novel downstream target of
      the proto-oncogene Myc that participates in controlling cell division and
      proliferation. Misu catalyzes the transfer of a methyl group from S-adenosyl-L
      methionine to carbon 5 of cytosines in tRNAs. It was previously shown to catalyze
      in vitro the intron-dependent formation of m ( 5) C at the first position of the
      anticodon (position 34) within the human pre-tRNA (Leu) (CAA). In addition, it
      was recently reported that C48 and C49 are methylated in vivo by Misu. We report
      here the expression of hMisu in Escherichia coli and its purification to
      homogeneity. We show that this enzyme methylates position 48 in tRNA (Leu) (CAA)
      with or without intron and positions 48, 49 and 50 in tRNA (Gly2) (GCC) in vitro.
      Therefore, hMisu is the enzyme responsible for the methylation of at least four
      cytosines in human tRNAs. By comparison, the orthologous yeast enzyme Trm4
      catalyzes the methylation of carbon 5 of cytosine at positions 34, 40, 48 or 49
      depending on the tRNAs.

PMID- 22995838
TI  - Human papillomavirus vaccine uptake, knowledge and attitude among 10th grade
      students in Berlin, Germany, 2010.
AB  - PURPOSE: Since March 2007, the Standing Committee on Vaccination (STIKO)
      recommends HPV vaccination for all 12-17 y-old females in Germany. In the absence
      of an immunization register, we aimed at assessing HPV-vaccination coverage and
      knowledge among students in Berlin, the largest city in Germany, to identify
      factors influencing HPV-vaccine uptake. METHODS: Self-administered questionnaires
      were distributed to 10th grade school students in 14 participating schools in
      Berlin to assess socio-demographic characteristics, knowledge, and statements on
      vaccinations. Vaccination records were reviewed. Multivariable statistical
      methods were applied to identify independent predictors for HPV-vaccine uptake
      among female participants. RESULTS: Between September and December 2010, 442
      students completed the questionnaire (mean age 15.1; range 14-19). In total
      281/442 (63.6%) students specified HPV correctly as a sexually transmitted
      infection. Of 238 participating girls, 161 (67.6%) provided their vaccination
      records. Among these, 66 (41.0%) had received the recommended three HPV-vaccine
      doses. Reasons for being HPV-unvaccinated were reported by 65 girls: Dissuasion
      from parents (40.2%), dissuasion from their physician (18.5%), and concerns about
      side-effects (30.8%) (multiple choices possible). The odds of being vaccinated
      increased with age (Odds Ratio (OR) 2.19, 95% Confidence Interval (CI) 1.16,
      4.15) and decreased with negative attitude toward vaccinations (OR = 0.33, 95%CI
      0.13, 0.84). CONCLUSIONS: HPV-vaccine uptake was low among school girls in
      Berlin. Both, physicians and parents were influential regarding their HPV
      vaccination decision even though personal perceptions played an important role as
      well. School programs could be beneficial to improve knowledge related to HPV and
      vaccines, and to offer low-barrier access to HPV vaccination.

PMID- 22995839
TI  - Therapeutic vaccines: the ultimate personalized therapy?
AB  - Personalized therapy is directed at obtaining maximal therapeutic effect on
      diseased tissue with minimal off-target side effects. Many classes of
      therapeutics have attempted to reach this ideal, only to fall well short.
      Therapeutic vaccines represent a novel class of therapies that can induce a
      dynamic immune response that, in theory, can continue to adapt and expand
      following initiation of vaccination. This adaptability, through epitope spreading
      or antigen cascade, can continuously refine a therapeutic immune response, making
      it more relevant to the patient's tumor. This active, dynamic, iterative process
      can continue long after the vaccine course has been completed. Recent clinical
      trials have provided further insight into the clinical activity of therapeutic
      vaccines, and offer guidance on clinical expectations following vaccine. The
      ongoing active sculpting of the immune response, along with the lack of
      significant side effects, uniquely positions therapeutic vaccines as perhaps the
      ultimate in personalized therapy.

PMID- 22995840
TI  - The white coat effect is not associated with additional increase of target organ
      damage in true resistant hypertension.
AB  - BACKGROUND AND OBJECTIVE: White coat effect (WCE) (i.e., the difference between
      office blood pressure [OBP] and awake ambulatory blood pressure monitoring
      [ABPM]) may be present in hypertensive individuals. The relationship between
      occurrence of WCE and target organ damage (TOD) has not yet been assessed in true
      resistant hypertension (RHTN). PATIENTS AND METHODS: RHTN patients were divided
      into two groups: RHTN with WCE (WCE, n=66) and RHTN without WCE (non-WCE, n=61).
      All patients were submitted to OBP measurement, ABPM, echocardiography and renal
      function evaluation in three visits. RESULTS: No differences were observed
      between the WCE and non-WCE groups regarding age, body mass index or gender. OBP
      were 169.8+/-15.8/95.1+/-14.0 (WCE) and 161.9+/-9.0/90.1+/-10.4mmHg (non-WCE),
      ABPM=143.0+/-12.8/86.1+/-9.9 (WCE) and 146.1+/-13.6/85.1+/-14.9mmHg (non-WCE). No
      statistical differences were observed between WCE and non-WCE subgroups with
      respect to left ventricular mass index (LVMI) (WCE=131+/-4.7; non-WCE=125+/
      2.9g/m(2)), creatinine clearance (WCE=78+/-4.7; non-WCE=80+/-3.6ml/min/m(2)) and
      microalbuminuria (MA) (WCE=44+/-8.4; non-WCE=49+/-6.8mg/g Cr). CONCLUSIONS: This
      finding may suggest that WCE is not associated with additional increase of TOD in
      true RHTN subjects.

PMID- 22995837
TI  - Plant-derived virus-like particles as vaccines.
AB  - Virus-like particles (VLPs) are self-assembled structures derived from viral
      antigens that mimic the native architecture of viruses but lack the viral genome.
      VLPs have emerged as a premier vaccine platform due to their advantages in
      safety, immunogenicity, and manufacturing. The particulate nature and high
      density presentation of viral structure proteins on their surface also render
      VLPs as attractive carriers for displaying foreign epitopes. Consequently,
      several VLP-based vaccines have been licensed for human use and achieved
      significant clinical and economical success. The major challenge, however, is to
      develop novel production platforms that can deliver VLP-based vaccines while
      significantly reducing production times and costs. Therefore, this review focuses
      on the essential role of plants as a novel, speedy and economical production
      platform for VLP-based vaccines. The advantages of plant expression systems are
      discussed in light of their distinctive posttranslational modifications, cost
      effectiveness, production speed, and scalability. Recent achievements in the
      expression and assembly of VLPs and their chimeric derivatives in plant systems
      as well as their immunogenicity in animal models are presented. Results of human
      clinical trials demonstrating the safety and efficacy of plant-derived VLPs are
      also detailed. Moreover, the promising implications of the recent creation of
      "humanized" glycosylation plant lines as well as the very recent approval of the
      first plant-made biologics by the U. S. Food and Drug Administration (FDA) for
      plant production and commercialization of VLP-based vaccines are discussed. It is
      speculated that the combined potential of plant expression systems and VLP
      technology will lead to the emergence of successful vaccines and novel
      applications of VLPs in the near future.

PMID- 22995841
TI  - [Essential tremor: update].

PMID- 22995842
TI  - [Ocular brucellosis].

PMID- 22995843
TI  - [Use of benzodiazepines according to the admission diagnosis].
AB  - BACKGROUND AND OBJECTIVE: Chronic consumption of benzodiazepines is common in
      elderly patients. The aim of the study was to analyse the possible differences
      between patients taking benzodiazepines and those without them. We also
      determined, among patients on benzodiazepines, if any differences were related to
      medical or surgical admissions. PATIENTS AND METHODS: We performed a prospective
      and multicentre study of 393 patients admitted consecutively for medical reasons
      to 6 geriatrics acute units; these patients were compared to 1,225 patients
      hospitalized for a hip fracture. We collected sociodemographic data, functional
      capacity by the Barthel's index (BI), comorbidity by the Charlson's index and
      cognitive impairment by the Pfeiffer test. RESULTS: We evaluated 1,618 patients,
      with a median age of 82.9 (6.5) years. Among patients admitted for medical
      causes, 581 (35.9%) were taking benzodiazepines chronically as did 449 (36.6%)
      patients in the hip fracture group (p=0.27). In the multivariate analysis,
      factors associated with the use of benzodiazepines included older age,
      institutionalization and a higher number of drug consumption. Differences
      according to the admission reason showed that patients admitted for medical
      causes lived more frequently in the community and had less falls, worse BI as
      well as a higher number of comorbidities and polypharmacy. CONCLUSIONS: More than
      one third of elderly patients hospitalized for medical or traumatology causes
      were taking benzodiazepines chronically. Different patients' profiles can be
      observed according to whether they are or not taking benzodiazepines and to the
      admission's cause in the subgroup of patients on benzodiazepines.

PMID- 22995844
TI  - [Incidence and prognosis implication of anemia in patients admitted with acute
      coronary syndrome].

PMID- 22995845
TI  - [Survival of haematologic patients admitted to an Intensive Care Unit. A 16 years
      study].
AB  - BACKGROUND AND OBJECTIVE: The survival of haematologic patients admitted to
      Intensive Care units (ICU) is so poor, that it is debatable whether they should
      be admitted or not to them. We aimed to find out the survival of these patients
      in an ICU to know if their admission is justified. PATIENTS AND METHOD:
      Retrospective study of 600 haematologic patients (49.4 +/- 16.4 years, 58.3%
      male) representing a total of 660 different admissions to the ICU of a university
      hospital, with a 6 months follow-up. Haematologic diseases were: leukaemia
      (50.5%), lymphoma (18.7%), myeloma (10.0%), myelodysplasic syndromes (4.2%),
      aplastic anaemia or bone marrow aplasia (3.3%), thrombotic microangiopathies and
      HELLP syndrome (7.4%), and others. RESULTS: A total of 37.5% of patients
      survived. Survival of thrombotic microangiopathies and HELLP syndrome was higher
      (81.8% of patients) than that of leukaemias (26.6%) and lymphomas (49.1%). When
      the reason for ICU admission was respiratory failure with or without septic
      shock, the survival was lower (20 and 27% of admissions respectively) than when
      it was septic shock alone (58.7%). Survival of mechanically ventilated patients
      was 14.6%, that of those treated with any renal replacement therapy 32.4% and
      that of patients with both treatments 13.8%. From all mechanically ventilated
      leukaemia or lymphoma patients, 10.3% survived (93 days in the ICU per life
      saved) but only 7.7% were alive 6 months later. CONCLUSIONS: Considering that the
      ICU survival was higher than 10% for all the groups studied, we conclude that
      admission of haematologic patients to the ICU is appropriate.

PMID- 22995846
TI  - [Recurrence risk in venous thromboembolic disease after anticoagulation
      discontinuation].
AB  - To determine the risk for recurrence of venous thromboembolic disease is
      essential to decide the optimum duration of treatment. Clinical risk factors,
      elevated D-dimer after anticoagulation withdrawal and the presence of residual
      deep vein thrombosis should be considered. In this article the risk factors and
      the reported risk models are reviewed.

PMID- 22995848
TI  - Phylogenetic relationship among East Asian species of the Stegana genus group
      (Diptera, Drosophilidae).
AB  - The phylogenetic relationship among 27 East Asian species of the Stegana genus
      group was reconstructed using DNA sequences of mitochondrial (COI and ND2) and
      nuclear (28S) genes. The results lent support to the current generic/subgeneric
      taxonomic classification in the genus group with the exceptions of the paraphyly
      of the genus Parastegana and the subgenus Oxyphortica in the genus Stegana. The
      ancestral areas and divergence times in the genus group were
      reconstructed/estimated, and accordingly, the biogeographical history of this
      important clade was discussed. It was proposed that, the evolution of the plant
      family Fagaceae, especially Quercus, may have played a certain role in
      facilitating the diversification of the Stegana genus group.

PMID- 22995847
TI  - [Levofloxacin hepatotoxicity].

PMID- 22995849
TI  - Molecular phylogeny of North American Branchiobdellida (Annelida: Clitellata).
AB  - Branchiobdellidans, or crayfish worms, are ectosymbiotic clitellate annelids
      associated primarily with freshwater crayfishes. The main objectives of our study
      were to infer a molecular phylogeny for the North American Branchiobdellida,
      examine its congruence with morphology-based hypotheses of relationships at the
      subfamily and genus level, and use our dataset to assess consistency of GenBank
      archived branchiobdellidan sequences. We used nucleotide sequence data from two
      mtDNA genes (COI and 16S rDNA) and three nuclear genes (28S rDNA, 18S rDNA, and
      ITS1) to estimate phylogenetic relationships among 47 described and one
      undescribed species of Branchiobdellida. We recovered a monophyletic
      branchiobdellidan clade with generally short branch lengths, suggesting that a
      large portion of the taxon has likely undergone a recent and rapid radiation in
      North America. Results from our phylogenetic analyses indicate that current
      taxonomic groupings are largely unsupported by the molecular data. All four
      subfamilies are either paraphyletic or polyphyletic, and only three of seven
      sampled non-monotypic genera were monophyletic. We found a high rate (49%) of
      inconsistency in GenBank-archived sequences, over 70% of which can be attributed
      to field- or laboratory-based error.

PMID- 22995850
TI  - Characterization of multi-walled carbon nanotube-polymer nanocomposites by
      scanning spreading resistance microscopy.
AB  - Nanocomposites of aligned multi-walled carbon nanotubes (CNTs) embedded in a
      polymer matrix yield a unique combination of thermal and electrical properties
      and mechanical strength. These properties are intimately related to the composite
      nanostructure and to the growth and processing conditions. The alignment of the
      tubes, the filling fraction and the contact junction between the nanotubes are
      key parameters controlling the composite electrical conductivity. For this
      purpose, a full description of the composite nanostructure is required. Among the
      non-destructive scanning probe techniques, scanning spreading resistance
      microscopy is found to be a powerful technique in identifying the carbon
      nanotubes with true nanometer resolution, thus competing with SEM and TEM
      imaging. Additionally, the technique provides valuable information about the
      electrical conduction mechanism within the composite structure. Indeed, by using
      a controlled contact force and an appropriate model of conduction at the
      nanoscale, the tip-CNT contact resistance, the CNT intrinsic resistance and the
      CNT-epoxy-CNT resistance junction are evaluated. This latter is found to be the
      factor controlling the overall electrical conductivity of the composite.

PMID- 22995851
TI  - Proxies and prevention of malaria in pregnancy.

PMID- 22995852
TI  - Malaria prevention in pregnancy, birthweight, and neonatal mortality: a meta
      analysis of 32 national cross-sectional datasets in Africa.
AB  - BACKGROUND: Low birthweight is a significant risk factor for neonatal and infant
      death. A prominent cause of low birthweight is infection with Plasmodium
      falciparum during pregnancy. Antimalarial intermittent preventive therapy in
      pregnancy (IPTp) and insecticide-treated mosquito nets (ITNs) significantly
      reduce the risk of low birthweight in regions of stable malaria transmission. We
      aimed to assess the effectiveness of malaria prevention in pregnancy (IPTp or
      ITNs) at preventing low birthweight and neonatal mortality under routine
      programme conditions in malaria endemic countries of Africa. METHODS: We used a
      retrospective birth cohort from national cross-sectional datasets in 25 African
      countries from 2000-10. We used all available datasets from multiple indicator
      cluster surveys, demographic and health surveys, malaria indicator surveys, and
      AIDS indicator surveys that were publically available as of 2011. We tried to
      limit confounding bias through exact matching on potential confounding factors
      associated with both exposure to malaria prevention (ITNs or IPTp with
      sulfadoxine-pyrimethamine) in pregnancy and birth outcomes, including local
      malaria transmission, neonatal tetanus vaccination, maternal age and education,
      and household wealth. We used a logistic regression model to test for
      associations between malaria prevention in pregnancy and low birthweight, and a
      Poisson model for the outcome of neonatal mortality. Both models incorporated the
      matched strata as a random effect, while accounting for additional potential
      confounding factors with fixed effect covariates. FINDINGS: We analysed 32
      national cross-sectional datasets. Exposure of women in their first or second
      pregnancy to full malaria prevention with IPTp or ITNs was significantly
      associated with decreased risk of neonatal mortality (protective efficacy [PE]
      18%, 95% CI 4-30; incidence rate ratio [IRR] 0.820, 95% CI 0.698-0.962), compared
      with newborn babies of mothers with no protection, after exact matching and
      controlling for potential confounding factors. Compared with women with no
      protection, exposure of pregnant women during their first two pregnancies to full
      malaria prevention in pregnancy through IPTp or ITNs was significantly associated
      with reduced odds of low birthweight (PE 21%, 14-27; IRR 0.792, 0.732-0.857), as
      measured by a combination of weight and birth size perceived by the mother, after
      exact matching and controlling for potential confounding factors. INTERPRETATION:
      Malaria prevention in pregnancy is associated with substantial reductions in
      neonatal mortality and low birthweight under routine malaria control programme
      conditions. Malaria control programmes should strive to achieve full protection
      in pregnant women by both IPTp and ITNs to maximise their benefits. Despite an
      attempt to mitigate bias and potential confounding by matching women on factors
      thought to be associated with access to malaria prevention in pregnancy and birth
      outcomes, some level of confounding bias possibly remains.

PMID- 22995853
TI  - The characterization and potential impact of melanoma cases with unknown
      thickness in the United States' Surveillance, Epidemiology, and End Results
      Program, 1989-2008.
AB  - BACKGROUND: In the United States, the Surveillance, Epidemiology, and End Results
      (SEER) Program is the authoritative source for population-based data on melanoma
      incidence and mortality. However, missing data on tumor thickness may lead to
      biased analyses in this frequently used database. We sought to characterize
      invasive melanomas with unknown thickness with emphasis on their association with
      melanoma survival, and to employ techniques to overcome the limitations of
      missing data on tumor thickness. METHODS: We conducted a retrospective cohort
      analysis of non-occult invasive melanomas in the SEER database from 1989 to 2008.
      RESULTS: Of 182184 cases, 24329 (13%) had unknown thickness. From 1989-1993 to
      2004-2008, the proportion of unknown thickness cases decreased from 22% to 9%
      (P(trend) < 0.001). Unknown thickness cases had a significantly increased risk of
      death due to melanoma (hazard ratio [HR] 3.09, 95% confidence interval [CI]:
      2.99, 3.19) than known thickness cases with an increasing trend over time
      (P(trend) < 0.001). In multivariate analysis, unknown thickness was found to be
      independently associated with poorer prognostic factors and lack of cancer
      directed surgical treatment. Melanoma survival of cases with unknown thickness
      appeared most similar to 2.01-4.00 mm thickness cases. Multiple imputation
      demonstrated that imputed tumor thickness was significantly associated with
      melanoma survival (HR 1.31, 95% CI: 1.30, 1.32) and Clark level (odds ratio [OR]
      1.85, 95% CI: 1.82, 1.89) though the strength of associations were not as strong
      as the associations of original SEER-coded known tumor thickness with melanoma
      survival (HR 1.46, 95% CI: 1.45, 1.47) and Clark level (OR 2.92, 95% CI 2.89,
      2.95), respectively. CONCLUSIONS: Exclusion of missing data on melanoma thickness
      from SEER introduces a selection bias that leads to an underestimation in the
      prevalence of fatal and likely thicker melanomas. Multiple imputation appears to
      be an effective tool to predict missing tumor thickness data.

PMID- 22995854
TI  - Prevention and self-management interventions are top priorities for
      osteoarthritis systematic reviews.
AB  - OBJECTIVE: To identify high-priority research questions for osteoarthritis
      systematic reviews with consideration of health equity and the social
      determinants of health (SDH). STUDY DESIGN AND SETTING: We consulted with experts
      and conducted a literature search to identify a priority-setting method that
      could be adapted to address the health equity and SDH. We selected the Global
      Evidence Mapping priority-setting method, and through consultations and
      consensus, we adapted the method to meet our objectives. This involves developing
      an evidence map of the existing systematic reviews on osteoarthritis; conducting
      one face-to-face workshop with patients and another one with clinicians,
      researchers, and patients; and conducting an online survey of patients to rank
      the top 10 research questions. We piloted the adapted method with the Cochrane
      Musculoskeletal Review Group to set research priorities for osteoarthritis.
      RESULTS: Our focus was on systematic reviews: we identified 34 high-priority
      research questions for osteoarthritis systematic reviews. Prevention and self
      management interventions, mainly diet and exercise, are top priorities for
      osteoarthritis systematic reviews. Evaluation against our predefined objectives
      showed that this method did prioritize SDH (50% of the research questions
      considered SDH). There were marked gaps: no high-priority topics were identified
      for access to care until patients had advanced disease-lifestyle changes once the
      disease was diagnosed. This method was felt feasible if conducted annually.
      CONCLUSION: We confirmed the utility of an adapted priority-setting method that
      is feasible and considers SDH. Further testing of this method is needed to assess
      whether considerations of health equity are prioritized and involve disadvantaged
      groups of the population.

PMID- 22995855
TI  - Development and pilot test of a process to identify research needs from a
      systematic review.
AB  - OBJECTIVE: To ensure appropriate allocation of research funds, we need methods
      for identifying high-priority research needs. We developed and pilot tested a
      process to identify needs for primary clinical research using a systematic review
      in gestational diabetes mellitus. STUDY DESIGN AND SETTING: We conducted eight
      steps: abstract research gaps from a systematic review using the Population,
      Intervention, Comparison, Outcomes, and Settings (PICOS) framework; solicit
      feedback from the review authors; translate gaps into researchable questions
      using the PICOS framework; solicit feedback from multidisciplinary stakeholders
      at our institution; establish consensus among multidisciplinary external
      stakeholders on the importance of the research questions using the Delphi method;
      prioritize outcomes; develop conceptual models to highlight research needs; and
      evaluate the process. RESULTS: We identified 19 research questions. During the
      Delphi method, external stakeholders established consensus for 16 of these 19
      questions (15 with "high" and 1 with "medium" clinical benefit/importance).
      CONCLUSION: We pilot tested an eight-step process to identify clinically
      important research needs. Before wider application of this process, it should be
      tested using systematic reviews of other diseases. Further evaluation should
      include assessment of the usefulness of the research needs generated using this
      process for primary researchers and funders.

PMID- 22995856
TI  - Estimating benefits and harms of screening across subgroups: the Canadian Task
      Force on Preventive Health Care integrates the GRADE approach and overcomes minor
      challenges.
AB  - OBJECTIVE: This paper describes the integration of the GRADE (Grading of
      Recommendations Assessment, Development and Evaluation) approach into their
      clinical preventive guideline development process by the new Canadian Task Force
      on Preventive Health Care. STUDY DESIGN: The GRADE approach focused the analytic
      framework and key questions on patient-important benefits and harms related to
      screening that incorporated detection, treatment, and follow-up. It also led to
      an explicit consideration of values and preferences and resource implications on
      the basis of the recommendations. RESULTS: There are challenges, however, in
      incorporating the GRADE approach to clinical prevention, as the randomized
      controlled trials in this field have needed to be very large and of long
      duration, given the rare occurrence of primary outcome events in asymptomatic
      individuals. We provide examples of how we met these challenges in relation to
      developing clinical guidelines for screening for breast cancer, cervical cancer,
      diabetes, hypertension, and depression in primary care settings. CONCLUSION: The
      focus on the patient-important outcomes was helpful in estimating effectiveness
      of screening approaches and providing explicit detailing of the basis of our
      recommendations across subgroups.

PMID- 22995857
TI  - NO/cGMP production is important for the endogenous peripheral control of
      hyperalgesia during inflammation.
AB  - Various studies have demonstrated the role of the nitric oxide (NO)/cGMP pathway
      in pain processing. Our group has also shown that this system participates in
      opioid-induced antinociception during peripheral inflammation. We have previously
      observed that inflammation mobilizes an endogenous opioidergic system to control
      hyperalgesia. Here, we investigated whether the NO/cGMP pathway underlies
      peripheral endogenous nociception control during inflammation. In this study, a
      pharmacological approach was used in conjunction with the rat paw pressure test
      to assess the effects of intraplantar NO synthase inhibitor NG-Nitro-l-arginine
      (NOArg), guanylyl cyclase inhibitor methylene blue (MB), phosphodiesterase-5
      inhibitor zaprinast (ZP), or NO precursor l-arginine injection on carrageenan
      induced hyperalgesia, which mimics an inflammatory process, or by prostaglandin
      E(2) (PGE(2)), which directly sensitizes nociceptors. Intraplantar carrageenan
      (62.5, 125, 250 or 500MUg) or PGE(2) (0.1, 0.5 or 2MUg) administration produced
      hyperalgesia, which manifested as a reduction in the rat nociceptive threshold to
      mechanical stimuli. NOArg (25, 50 or 100MUg/paw) and MB (125, 250 or 500MUg/paw)
      induced significant and dose-dependent reductions in the nociceptive threshold of
      carrageenan-induced (125MUg/paw) hyperalgesia, but not PGE(2)-induced
      (0.5MUg/paw) hyperalgesia. This was a local effect because it did not produce any
      modifications in the contralateral paw. Both Zaprinast (100, 200 or 400MUg/paw)
      and l-arginine (100, 200 or 400MUg/paw) significantly counteracted carrageenan
      induced hyperalgesia (250MUg/paw), yielding an increase in the nociceptive
      threshold compared with the control. Zaprinast (200MUg/paw) or l-arginine
      (400MUg/paw) did not produce an antinociceptive effect in the contralateral paw,
      indicating local action. In addition, at the same dose that was able to modify
      carrageenan-induced hyperalgesia, neither zaprinast nor l-arginine modified
      PGE(2) (2MUg) injection-induced hyperalgesia of the rat paw. Taken together,
      these results indicate that the l-arginine/NO/cGMP pathway functions as an
      endogenous modulator of peripheral inflammatory hyperalgesia.

PMID- 22995858
TI  - Comparison of the immune responses in BALB/c mice following immunization with DNA
      based and live attenuated vaccines delivered via different routes.
AB  - The objective of this study was to compare immune responses induced in BALB/c
      mice following immunization with pcDNA-GPV-VP2 DNA by gene gun bombardment (6
      MUg) or by intramuscular (im) injection (100 MUg) with the responses to live
      attenuated vaccine by im injection (100 MUl). pcDNA3.1 (+) and physiological
      saline were used as controls. Peripheral blood samples were collected at 3, 7,
      14, 21, 28, 35, 49, 63, 77 and 105 d after immunization. T lymphocyte
      proliferation was analyzed by MTT assay and enumeration of CD4(+), and CD8(+) T
      cell populations in peripheral blood was performed by flow cytometric analysis.
      Indirect ELISA was used to detect IgG levels. Cellular and humoral responses were
      induced by pcDNA-GPV-VP2 DNA and live virus vaccines. No differences were
      observed in T cell proliferation and CD8(+) T cell responses induced by the
      genetic vaccine regardless of the route of delivery. However, CD4(+) T cell
      responses and humoral immunity were enhanced in following gene gun immunization
      compared with im injection of the genetic vaccine. Cellular and humoral immunity
      was enhanced in following gene gun delivery of the genetic vaccine compared with
      the live attenuated vaccine. In conclusion, the pcDNA-GPV-VP2 DNA vaccine induced
      enhanced cellular and humoral immunity compared with that induced by the live
      attenuated vaccine.

PMID- 22995859
TI  - Quantification of tip-broadening in non-contact atomic force microscopy with
      carbon nanotube tips.
AB  - Carbon nanotube terminated atomic force microscopy (AFM) probes have been used
      for the imaging of 5 nm wide surface supported Pt nanoclusters by non-contact
      (dynamic mode) AFM in an ultra-high vacuum. The results are compared to AFM
      measurements done with conventional Si-tips, as well as with transmission
      electron microscopy images, which give accurate measures for cluster widths.
      Despite their ideal aspect ratio, tip-broadening is concluded to be a severe
      problem even when imaging with carbon nanotube tips, which overestimates the
      cluster width by several times the nominal width of the nanotube tip. This
      broadening is attributed to a bending of the carbon nanotubes, and not to pure
      geometrical factors, which coincidentally results in a significant improvement
      for relative height measurements of tightly spaced high aspect ratio structures,
      as compared to what can be achieved with geometrically limited conventional
      probes. Superior durability also stands out as a defining feature of carbon
      nanotube terminated probes, allowing them to give results with a greatly enhanced
      reproducibility.

PMID- 22995860
TI  - Differential roles of cyclin-dependent kinase 5 in tangential and radial
      migration of cerebellar granule cells.
AB  - The cerebellar granule cell is a unique neuron which undergoes tangential
      migration along axonal tracts and radial migration along glial fibers
      sequentially during postnatal development. Little is known about molecular bases
      of the differential kinetics of tangential and radial migration. Here we
      developed a time-lapse imaging assay for tangential migration of cerebellar
      granule cells, and investigated comparative contributions of cyclin-dependent
      kinase 5 (CDK5), a key regulator of neuronal migration, in tangential and radial
      migration of granule cells in vivo and in organotypic cultures. Overexpression of
      a dominant-negative form of CDK5 severely disrupted cell morphology and somal
      movement during radial migration, while it only moderately affected tangential
      migration. Dominant-negative inhibition of CDK5 induced formation of ectopic
      radial processes in granule cells in vivo which aberrantly elongated into the
      white matter in the cerebellum. Live imaging of granule cell migration in
      cerebellar slices revealed that CDK5 regulates not only nuclear migration but
      also centrosome movement during radial migration. These findings suggest a mode
      specific function of CDK5 in neuronal migration.

PMID- 22995861
TI  - Carbon-14 transfer into potato plants following a short exposure to an
      atmospheric 14CO2 emission: observations and model predictions.
AB  - To improve the understanding of the environmental (14)C behaviour, the
      International Atomic Energy Agency (IAEA) coordinated a Tritium and C-14 Working
      Group (T&C WG) in its EMRAS (Environmental Modelling for Radiation Safety)
      programme. One of the scenarios developed in the frame of T&C WG involved the
      prediction of time dependent (14)C concentrations in potato plants. The
      experimental data used in the scenario were obtained from a study in which
      potatoes (Solanum tuberosum cv. Romano) were exposed to atmospheric (14)CO(2) in
      a wind tunnel. The observations were used to test models that predict temporal
      changes in (14)C concentrations in leaves at each sampling time for each
      experiment and (14)C concentrations in tubers at the final harvest of each
      experiment. The experimental data on (14)C dynamics in leaves are poorly
      reproduced by most of the models, but the predicted concentrations in tubers are
      in good agreement with the observations.

PMID- 22995862
TI  - Maximum reasonable radioxenon releases from medical isotope production facilities
      and their effect on monitoring nuclear explosions.
AB  - Fission gases such as (133)Xe are used extensively for monitoring the world for
      signs of nuclear testing in systems such as the International Monitoring System
      (IMS). These gases are also produced by nuclear reactors and by fission
      production of (99)Mo for medical use. Recently, medical isotope production
      facilities have been identified as the major contributor to the background of
      radioactive xenon isotopes (radioxenon) in the atmosphere (Stocki et al., 2005;
      Saey, 2009). These releases pose a potential future problem for monitoring
      nuclear explosions if not addressed. As a starting point, a maximum acceptable
      daily xenon emission rate was calculated, that is both scientifically defendable
      as not adversely affecting the IMS, but also consistent with what is possible to
      achieve in an operational environment. This study concludes that an emission of 5
      * 10(9) Bq/day from a medical isotope production facility would be both an
      acceptable upper limit from the perspective of minimal impact to monitoring
      stations, but also appears to be an achievable limit for large isotope producers.

PMID- 22995864
TI  - Effect of short-term reduced physical activity on cardiovascular risk factors in
      active lean and overweight middle-aged men.
AB  - OBJECTIVES: An experimental reduction in physical activity is a useful tool for
      exploring the health benefits of physical activity. This study investigated
      whether similarly-active overweight men show a more pronounced response to
      reduced physical activity than their lean counterparts because of their
      atherogenic phenotype (i.e., greater abdominal adiposity). METHODS: From 115
      active men aged 45-64years, we recruited nine active lean (waist circumference
      <84cm) and nine active central overweight men (waist circumference >94cm).
      Fasting blood samples and responses to an oral glucose tolerance test (OGTT) were
      measured at baseline and following one week of reduced physical activity to
      simulate sedentary levels (removal of structured exercise and reduced habitual
      physical activity). RESULTS: Glucose and insulin areas under the curve (AUC),
      CRP, ALT, TAG were all higher in the overweight group and remained so throughout
      (P<0.05). Insulin and glucose AUC responses to an OGTT, as well as fasting
      triglyceride (TAG) concentrations, increased in both groups as a result of the
      intervention (P<0.05). There was no change in interleukin-6, C-reactive protein
      (CRP), Tumour Necrosis Factor-alpha, soluble intracellular adhesion molecule 1,
      or alanine transaminase (ALT). CONCLUSION: One-week of reduced activity similarly
      impaired glucose control and increased fasting TAG in both lean and overweight
      men. Importantly, in spite of very similar (high) levels of habitual physical
      activity, central overweight men displayed a poorer profile for various
      inflammatory and metabolic outcomes (CRP, ALT, TAG, glucose AUC and insulin AUC).

PMID- 22995863
TI  - iNOS inhibitor, L-NIL, reverses burn-induced glycogen synthase kinase-3beta
      activation in skeletal muscle of rats.
AB  - OBJECTIVES: Recent studies suggest that activation of glycogen synthase kinase
      (GSK)-3beta may be involved in burn injury-induced metabolic derangements and
      protein breakdown in skeletal muscle. However, the mechanism for GSK-3beta
      activation after burn injury is unknown. To investigate the role of inducible
      nitric oxide synthase (iNOS) in this scenario, a major mediator of inflammation,
      we examined the effects of a specific inhibitor for iNOS, L-NIL, on GSK-3beta
      activity in skeletal muscle of burned rats. MATERIALS/METHODS: Full-thickness
      third degree burn injury comprising 40% of total body surface area was produced
      under anesthesia in male Sprague-Dawley rats (160-190g) by immersing the back of
      the trunk for 15s and the abdomen for 8s in 80 degrees C water. Burned and sham
      burned rats were treated with L-NIL (60mg/kg BW, b.i.d., IP) or phosphate
      buffered saline for three days. GSK-3beta activity in skeletal muscle was
      evaluated by immune complex kinase assay, and by phosphorylation status of GSK
      3beta and its endogenous substrate, glycogen synthase. RESULTS: GSK-3beta
      activity was increased in a time-dependent manner in skeletal muscle after burn
      injury, concomitant with the induction of iNOS expression. iNOS inhibitor, L-NIL,
      reverted the elevated GSK-3beta activity in skeletal muscle of burned rats,
      although L-NIL did not alter GSK-3beta activity in sham-burned rats. CONCLUSIONS:
      Our results clearly indicate that iNOS plays an important role in burn injury
      induced GSK-3beta activation in skeletal muscle. These findings suggest that iNOS
      may contribute to burn injury-induced metabolic derangements, in part, by
      activating GSK-3beta.

PMID- 22995865
TI  - A residential summer camp can reduce body fat and improve health-related quality
      of life in obese children.
AB  - In an earlier report, we showed that a 2-week, residential summer camp (Kamp
      K'aana) led to improved body weight, body mass index, body mass index z score,
      and self-esteem among obese children. To assess whether improvements in body
      weight and self-esteem translate into improvement in body fat and weight-related
      quality of life, we measured the changes in body fat by bioimpedance and quality
      of life by Impact of Weight on Quality of Life instrument on 42 multiethnic obese
      children who took part in our Kamp K'aana program. Significant reduction in body
      fat was detected with significant improvements in the weight-related quality of
      life scores.

PMID- 22995866
TI  - Two intrapancreatic tumors in a teenager with cystic fibrosis.

PMID- 22995867
TI  - Global efforts to address severe acute malnutrition.

PMID- 22995868
TI  - The economics of health care delivery.

PMID- 22995869
TI  - The anatomical assessment of disorders of sex development (DSD).
AB  - The assessment of abnormal anatomy in cases of DSD is important to aid diagnosis,
      understand the aetiology and severity of the condition, guide management and
      assess the outcomes of treatment. In this paper we present a systematic approach
      to this assessment which will provide a means by which the multiple disciplines
      who manage patients with these rare and complex conditions can communicate and
      thus improve overall care.

PMID- 22995870
TI  - Source of angiopoietin-2 in the sera of women during pregnancy.
AB  - Placental development requires coordinated angiogenesis regulated by multiple
      factors including angiopoietins. Previously we demonstrated that the
      concentration of angiopoietin-2 (Ang-2) in the sera of women rises markedly in
      pregnancy in early gestation. This increase is reduced in pregnancies
      subsequently complicated by intrauterine growth restriction (IUGR). We now show
      that the concentration of Ang-2, but not Ang-1, in maternal serum is increased
      during normal pregnancy, peaking at the end of the first trimester. We also
      demonstrate that a key source of the elevated Ang-2 levels during pregnancy is
      decidual endothelial cells (DECs) but not cytotrophoblasts. Secretion of Ang-2 by
      DECs relies on the release from intracellular stores and the synthesis of new Ang
      2 protein and is regulated by serum factors at a translational level. Further
      studies on the role of Ang-2 during pregnancy are warranted as well as the
      evaluation of Ang-2 as a marker to predict adverse pregnancy outcomes.

PMID- 22995871
TI  - Calcium tips the balance: a microtubule plus end to lattice binding switch
      operates in the carboxyl terminus of BPAG1n4.
AB  - Microtubules (MTs) are integral to numerous cellular functions, such as cell
      adhesion, differentiation and intracellular transport. Their dynamics are largely
      controlled by diverse MT-interacting proteins, but the signalling mechanisms that
      regulate these interactions remain elusive. In this report, we identify a rapid,
      calcium-regulated switch between MT plus end interaction and lattice binding
      within the carboxyl terminus of BPAG1n4. This switch is EF-hand dependent, and
      mutations of the EF-hands abolish this dynamic behaviour. Our study thus uncovers
      a new, calcium-dependent regulatory mechanism for a spectraplakin, BPAG1n4, at
      the MT plus end.

PMID- 22995872
TI  - Stability and inactivation of vesicular stomatitis virus, a prototype
      rhabdovirus.
AB  - Viruses may remain infectious outside the host cell for considerable time and
      represent a source of accidental infection if not properly inactivated. In this
      study, the survival of vesicular stomatitis virus (VSV) in suspension and dried
      on surfaces was analyzed. In addition, the sensitivity of VSV to disinfectants
      and physicochemical changes was investigated. VSV showed a notable stability in
      suspension at 4 degrees C with virus titers remaining high over several weeks.
      The presence of serum proteins had a stabilizing effect on virus infectivity,
      whereas elevated temperatures reduced survival times. VSV dried on polystyrene,
      glass or stainless steel surfaces remained infectious for at least 6 days at
      ambient temperature. VSV showed a remarkable resistance to extreme pH in
      particular in the alkaline range, but could be rapidly inactivated by heating at
      55 degrees C or higher. The virus was highly sensitive to inactivation by
      commonly used disinfectants such as aldehydes, alcohols, and detergents. The high
      stability of VSV on surfaces and in suspension may facilitate dissemination of
      the virus in livestock by contaminated feeding and water troughs, hands, and
      milking equipment. This knowledge on the sensitivity of VSV to disinfectants will
      help to set up appropriate hygiene measures.

PMID- 22995873
TI  - Porcine reproductive and respiratory syndrome virus induces pronounced immune
      modulatory responses at mucosal tissues in the parental vaccine strain VR2332
      infected pigs.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease
      of pigs caused by PRRS virus (PRRSV). The PRRSV VR2332 is the prototype North
      American parental strain commonly used in the preparation of vaccines. Goal of
      this study was to understand missing information on VR2332 induced immune
      modulation at the lungs and lymphoid tissues, the sites of PRRSV replication.
      Pigs were infected intranasally and samples collected at post-infection day (PID)
      15, 30, and 60. Microscopically, lungs had moderate interstitial pneumonia, and
      the virus was detected in all the tested tissues. Peak antibody response and the
      cytokine IFN-gamma secretion were detected at PID 30, with increased TGF-beta
      until PID 60. Population of CD8(+), CD4(+), and CD4(+)CD8(+)T cells, Natural
      killer (NK) cells, and gammadelta T cells in the lungs and lymphoid tissues were
      significantly modulated favoring PRRSV persistence. The NK cell-mediated
      cytotoxicity was significantly reduced in infected pigs. In addition, increased
      population of immunosuppressive T-regulatory cells (Tregs) and associated
      cytokines were also observed in VR2332 strain infected pigs.

PMID- 22995874
TI  - Phylogenetic and structural studies of a novel equine papillomavirus identified
      from aural plaques.
AB  - Papillomaviruses (PVs) infect a wide range of animal species and show great
      genetic diversity. To date, excluding equine sarcoids, only three species of PVs
      were identified associated with lesions in horses: Equus caballus papillomavirus
      1 (EcPV1-cutaneous), EcPV2 (genital) and EcPV3 (aural plaques). In this study, we
      identified a novel equine PV from aural plaques, which we designated EcPV4.
      Cutaneous samples from horses with lesions that were microscopically diagnosed as
      aural plaques were subjected to DNA extraction, amplification and sequencing.
      Rolling circle amplification and inverse PCR with specific primers confirmed the
      presence of an approximately 8 kb circular genome. The full-length EcPV4 L1 major
      capsid protein sequence has 1488 nucleotides (495 amino acids). EcPV4 had a
      sequence identity of only 53.3%, 60.2% and 51.7% when compared with the published
      sequences for EcPV1, EcPV2 and EcPV3, respectively. A Bayesian phylogenetic
      analysis indicated that EcPV4 clusters with EcPV2, but not with EcPV1 and EcPV3.
      Using the current PV classification system that is based on the nucleotide
      sequence of L1, we could not define the genus of the newly identified virus.
      Therefore, a structural analysis of the L1 protein was carried out to aid in this
      classification because EcPV4 cause lesion similar to the lesion caused by EcPV3.
      A comparison of the superficial loops demonstrated a distinct amino acid
      conservation pattern between EcPV4/EcPV2 and EcPV4/EcPV3. These results
      demonstrate the presence of a new equine PV species and that structural studies
      could be useful in the classification of PVs.

PMID- 22995875
TI  - Use of invasive strategy in non-ST-segment elevation myocardial infarction is a
      major determinant of improved long-term survival: FAST-MI (French Registry of
      Acute Coronary Syndrome).
AB  - OBJECTIVES: This study sought to assess the impact of invasive strategy (IS)
      versus a conservative strategy (CS) on in-hospital complications and 3-year
      outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI)
      from the FAST-MI (French Registry of Acute Coronary Syndrome). BACKGROUND:
      Results from randomized trials comparing IS and CS in patients with NSTEMI are
      conflicting. METHODS: Of the 3,670 patients in FAST-MI, which included patients
      with acute myocardial infarction (within 48 h) over a 1-month period in France at
      the end of 2005, 1,645 presented with NSTEMI. RESULTS: Of the 1,645 patients
      analyzed, 80% had an IS. Patients in the IS group were younger (67 +/- 12 years
      vs. 80 +/- 11 years), less often women (29% vs. 51%), and had a lower GRACE
      (Global Registry of Acute Coronary Events) risk score (137 +/- 36 vs. 178 +/- 34)
      than patients treated with CS. In-hospital mortality and blood transfusions were
      significantly more frequent in patients with CS versus IS (13.1% vs. 2.0%, 9.1%
      vs. 4.6%). Use of IS was associated with a significant reduction in 3-year
      mortality and cardiovascular death (17% vs. 60%, adjusted hazard ratio [HR]:
      0.44, 95% confidence interval [CI]: 0.35 to 0.55 and 8% vs. 36%, adjusted HR:
      0.37, 95% CI: 0.27 to 0.50). After propensity score matching (181 patients per
      group), 3-year survival was significantly higher in patients treated with IS.
      CONCLUSIONS: In a real-world setting of patients admitted with NSTEMI, the use of
      IS during the initial hospital stay is an independent predictor of improved 3
      year survival, regardless of age. (French Registry of Acute Coronary Syndrome
      [FAST-MI]; NCT00673036).

PMID- 22995876
TI  - Non-ST-segment elevation myocardial infarction: revascularization for everyone?

PMID- 22995878
TI  - Don't forget the intervention in very elderly persons with acute coronary
      syndromes.

PMID- 22995877
TI  - Early aggressive versus initially conservative treatment in elderly patients with
      non-ST-segment elevation acute coronary syndrome: a randomized controlled trial.
AB  - OBJECTIVES: This study sought to determine the risk versus benefit ratio of an
      early aggressive (EA) approach in elderly patients with non-ST-segment elevation
      acute coronary syndromes (NSTEACS). BACKGROUND: Elderly patients have been
      scarcely represented in trials comparing treatment strategies in NSTEACS.
      METHODS: A total of 313 patients >= 75 years of age (mean 82 years) with NSTEACS
      within 48 h from qualifying symptoms were randomly allocated to an EA strategy
      (coronary angiography and, when indicated, revascularization within 72 h) or an
      initially conservative (IC) strategy (angiography and revascularization only for
      recurrent ischemia). The primary endpoint was the composite of death, myocardial
      infarction, disabling stroke, and repeat hospital stay for cardiovascular causes
      or severe bleeding within 1 year. RESULTS: During admission, 88% of the patients
      in the EA group underwent angiography (55% revascularization), compared with 29%
      (23% revascularization) in the IC group. The primary outcome occurred in 43
      patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio
      [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of
      mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95%
      CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did
      not differ between groups. The primary endpoint was significantly reduced in
      patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80),
      but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for
      interaction = 0.03). CONCLUSIONS: The present study does not allow a definite
      conclusion about the benefit of an EA approach when applied systematically among
      elderly patients with NSTEACS. The finding of a significant interaction for the
      treatment effect according to troponin status at baseline should be confirmed in
      a larger size trial. (Italian Elderly ACS Study; NCT00510185).

PMID- 22995879
TI  - Outcomes of patients with prior coronary artery bypass grafting and acute
      coronary syndromes: analysis from the ACUITY (Acute Catheterization and Urgent
      Intervention Triage Strategy) trial.
AB  - OBJECTIVES: This study sought to assess the contemporary outcomes of patients
      with prior coronary artery bypass graft (CABG) who present with moderate and high
      risk acute coronary syndromes (ACS) and are treated with an early invasive
      strategy and contemporary antithrombin regimens. BACKGROUND: The prognosis of
      patients with ACS and prior CABG in relation to triage strategy and contemporary
      antithrombotic regimens is unknown. METHODS: In the ACUITY (Acute Catheterization
      and Urgent Intervention Triage Strategy) trial, 2,475 of 13,764 patients (18.0%)
      with ACS managed with an early invasive strategy had previously undergone CABG.
      Their outcomes were examined according to treatment and randomized antithrombin
      regimen. RESULTS: Prior CABG was associated with older age, more frequent
      comorbidities, higher Thrombolysis In Myocardial Infarction risk score, and lower
      left ventricular ejection fraction. Patients with versus without prior CABG were
      less likely to undergo (repeat) CABG and were more likely to be managed
      medically. At 1 year, patients with versus without prior CABG had higher rates of
      major adverse cardiac events (MACE) (22.5% vs. 15.2%, p < 0.0001) due to greater
      mortality (5.4% vs. 3.9%, p < 0.0001), myocardial infarction (10.0% vs. 6.8%, p <
      0.0001), and unplanned revascularization (13.1% vs. 8.2%, p < 0.0001). History of
      CABG was an independent predictor of MACE. The 1-year MACE rates were not
      significantly different after randomization to bivalirudin versus heparin plus a
      glycoprotein IIb/IIIa inhibitor (odds ratio: 1.24, 95% confidence interval: 0.90
      to 1.70). CONCLUSIONS: Despite the progress in the treatment of coronary artery
      disease, patients with prior CABG and ACS have a poor prognosis, substantially
      worse than for those without prior CABG. Whereas bivalirudin monotherapy was an
      acceptable treatment for these patients, it did not improve their prognoses.

PMID- 22995880
TI  - Association between angiographic complications and clinical outcomes among
      patients with acute coronary syndrome undergoing percutaneous coronary
      intervention: an EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST
      Segment Elevation Acute Coronary Syndrome) angiographic substudy.
AB  - OBJECTIVES: The goal of this analysis was to determine the association between
      intraprocedural complications and clinical outcomes among patients with high-risk
      non-ST-segment elevation acute coronary syndrome (NSTEACS) undergoing
      percutaneous coronary intervention (PCI). BACKGROUND: Among patients undergoing
      PCI for NSTEACS, the relationship between intraprocedural complications and
      clinical outcomes, independent of epicardial and myocardial perfusion, has not
      been well characterized. METHODS: The EARLY ACS (Early Glycoprotein IIb/IIIa
      Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome) trial enrolled
      9,406 patients with high-risk NSTEACS undergoing an early invasive strategy. Of
      these, 1,452 underwent angiographic assessment in an independent core laboratory
      and did not have a myocardial infarction (MI) between enrollment and angiography.
      We assessed the relationship between abrupt closure, loss of side branch(es),
      distal embolization, and no-reflow phenomenon and 30-day clinical outcomes in
      these patients. RESULTS: Of the patients, 166 (11.4%) experienced an
      intraprocedural complication. Baseline clinical characteristics were similar
      between patients who did and did not have complications. The 30-day composite of
      death or MI was significantly higher among patients with an intraprocedural
      complication (28.3% vs. 7.8%, odds ratio [OR]: 4.68, 95% confidence interval
      [CI]: 3.2 to 7.0, p < 0.001). Individually, both mortality (3.0% vs. 0.9%, OR:
      3.60, 95% CI: 1.2 to 10.5, p = 0.019) and MI (27.1% vs. 7.4%, OR: 4.66, 95% CI:
      3.1 to 7.0, p < 0.001) were significantly increased. After adjusting for
      differences in post-PCI epicardial and myocardial perfusion, the association with
      30-day death or MI remained significant. CONCLUSIONS: Among high-risk NSTEACS
      patients undergoing an invasive strategy, the incidence of intraprocedural
      complications is high, and the occurrence of these complications is associated
      with worse clinical outcomes independent of epicardial and myocardial perfusion.
      (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-segment Elevation
      Acute Coronary Syndrome [EARLY ACS]; NCT00089895).

PMID- 22995881
TI  - Unrestricted use of 2 new-generation drug-eluting stents in patients with acute
      myocardial infarction: a propensity score-matched analysis.
AB  - OBJECTIVES: This study sought to compare everolimus-eluting stents (EES) with
      zotarolimus-eluting stents (ZES) in patients with acute myocardial infarction
      (AMI). BACKGROUND: There is a paucity of data to exclusively evaluate the safety
      and efficacy of second-generation drug-eluting stents (DES) in the setting of
      AMI. METHODS: The present study enrolled 3,309 AMI patients treated with ZES (n =
      1,608) or EES (n = 1,701) in a large-scale, prospective, multicenter registry
      KAMIR (Korea Acute Myocardial Infarction Registry). Propensity score matching was
      applied to adjust for differences in baseline clinical and angiographic
      characteristics, producing a total of 2,646 patients (1,343 receiving ZES, and
      1,343 receiving EES). Target lesion failure (TLF) was defined as the composite of
      cardiac death, recurrent nonfatal myocardial infarction, or target lesion
      revascularization. Major clinical outcomes at 1 year were compared between the 2
      propensity score-matched groups. RESULTS: After propensity score matching,
      baseline clinical and angiographic characteristics were similar between the 2
      groups. Clinical outcomes of the propensity score-matched patients showed that,
      despite similar incidences of recurrent nonfatal myocardial infarction and in
      hospital and 1-year mortality, patients in the EES group had significantly lower
      rates of TLF (6.5% vs. 8.7%, p = 0.029) and probable or definite stent thrombosis
      (0.3% vs. 1.6%, p < 0.001), compared with those in the ZES group. Furthermore,
      there was a numerically lower rate of target lesion revascularization (1.2% vs.
      2.2%, p = 0.051) in the EES group than in the ZES group. CONCLUSIONS: In this
      propensity-matched comparison, EES seems to be superior to ZES in reducing TLF
      and stent thrombosis in patients with AMI.

PMID- 22995882
TI  - Long-term vascular healing in response to sirolimus- and paclitaxel-eluting
      stents: an optical coherence tomography study.
AB  - OBJECTIVES: This study sought to assess stent strut coverage, malapposition,
      protrusion, and coronary evaginations as markers of healing 5 years after
      implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents
      (PES), by optical coherence tomography (OCT). BACKGROUND: Early-generation drug
      eluting stents have been shown to delay vascular healing. METHODS: A total of 88
      event-free patients with 1 randomly selected lesion were suitable for final OCT
      analysis 5 years after drug-eluting stent implantation. The analytical approach
      was based on a hierarchical Bayesian random-effects model. RESULTS: OCT analysis
      was performed at 5 years in 41 SES lesions with 6,380 struts, and in 47 PES
      lesions with 6,782 struts. A total of 196 struts were uncovered in SES (1.5%)
      compared with 185 struts in PES lesions (1.0%, 95% credibility interval [CrI]:
      0.5 to 1.6; p = 0.32). Malapposed struts were present in 1.2% of SES compared
      with 0.7% of PES struts (0.7%, 95% CrI: 0.03 to 1.6; p = 0.23). Protruding struts
      were more frequent among SES (n = 114; 0.8%) than PES lesions (n = 24; 0.1%, 95%
      CrI: 0.3 to 1.3; p < 0.01). Coronary evaginations were more common among SES-
      than PES-treated lesions (17 vs. 7 per 100 cross sections, p = 0.003). During
      extended clinical follow-up, 2 patients suffered from very late stent thrombosis
      showing a high degree of malapposition, protrusion, and coronary evaginations at
      the time of OCT investigation. CONCLUSIONS: Early-generation drug-eluting stents
      show a similar degree of strut coverage and malapposition at 5 years of follow
      up. Despite an overall low degree of uncovered and malapposed struts in event
      free patients, some lesions show a clustering of these characteristics,
      indicating a heterogeneous healing response, which may be the source for very
      late adverse events.

PMID- 22995883
TI  - Association between periprocedural bleeding and long-term outcomes following
      percutaneous coronary intervention in older patients.
AB  - OBJECTIVES: The authors sought to describe the association between post
      procedural bleeding and long-term recurrent bleeding, major adverse cardiac
      events (MACE), and mortality among older patients undergoing percutaneous
      coronary intervention (PCI). BACKGROUND: Bleeding complications after PCI are
      associated with an increased risk for acute morbidity and long-term mortality,
      but the association of these bleeding complications with other events is unknown.
      METHODS: Patients entered into the National Cardiovascular Data Registry (NCDR)
      CathPCI Registry (n = 461,311; 946 sites) from January 2004 to December 2008 were
      linked with claims from the Centers for Medicare & Medicaid Services and grouped
      according to in-hospital post-PCI bleeding. The association between post-PCI
      bleeding and 1-, 12-, and 30-month readmission for bleeding, MACE, and all-cause
      mortality was examined with Cox regression that included patient and procedural
      characteristics using no bleeding as the reference. RESULTS: Overall, 3.1% (n =
      14,107) of patients experienced post-PCI bleeding. Patients who bled were older,
      more often female, had more medical comorbidities, less often received
      bivalirudin, and more often underwent PCI via the femoral approach. After
      adjustment, bleeding after the index procedure was significantly associated with
      readmission for bleeding (adjusted hazard ratios [95% confidence interval]: 1
      month, 1.54 [1.42 to 1.67]; 12 months, 1.52 [1.40 to 1.66]; 30 months, 1.29 [1.11
      to 1.50]), MACE (1 month, 1.11 [1.07 to 1.15]; 12 months, 1.17 [1.13 to 1.21]; 30
      months, 1.12 [1.06 to 1.19]) and all-cause mortality (1 month, 1.32 [1.26 to
      1.38]; 12 months, 1.33 [1.27 to 1.40]); 30 months, 1.22 [1.15 to 1.30]).
      CONCLUSIONS: Post-PCI bleeding complications are associated with an increased
      risk for short- and long-term recurrent bleeding, MACE, and all-cause mortality.
      These data underscore the prognostic importance of periprocedural bleeding and
      the need for identifying strategies to reduce long-term bleeding risk among
      patients undergoing PCI.

PMID- 22995884
TI  - Coronary endothelial dysfunction distal to stent of first-generation drug-eluting
      stents.
AB  - OBJECTIVES: This study sought to evaluate the relationship between coronary
      endothelial function and neointimal coverage after drug-eluting stent (DES)
      implantation. BACKGROUND: The mechanisms of endothelial dysfunction after DES
      implantation remain to be fully elucidated. We hypothesized that poor neointimal
      coverage after DES implantation may be associated with endothelial dysfunction
      distal to the stent site. METHODS: Sixty-six stable angina patients treated with
      a first-generation DES were enrolled. At 9-month follow-up, coronary endothelial
      function was evaluated with intracoronary infusion of incremental doses of
      acetylcholine (10(-8), 10(-7), and 10(-6) mol/l) and nitroglycerin (200 MUg).
      Vascular responses at the segments proximal and distal to the stent site were
      angiographically and quantitatively measured. At the same time, the degree of
      neointimal coverage was evaluated using coronary angioscopy and classified into 4
      grades: 0 (no coverage) to 3 (full coverage). RESULTS: We divided the subjects
      into poor-coverage (grades 0 to 1, n = 33) and good-coverage (grades 2 to 3, n =
      33) groups. Acetylcholine induced dose-dependent coronary vasoconstrictions in
      both groups. At the segment distal to the stent, the magnitude of
      vasoconstriction to acetylcholine in the poor-coverage group was significantly
      greater than in the good-coverage group (p < 0.001), whereas vasomotor responses
      proximal to the stent and vasodilation by nitroglycerine were similar between the
      2 groups. CONCLUSIONS: Coronary endothelial dysfunction distal to the stent was
      associated with poor neointimal coverage after DES implantation.

PMID- 22995886
TI  - Working toward a frailty index in transcatheter aortic valve replacement: a major
      move away from the "eyeball test".

PMID- 22995885
TI  - The impact of frailty status on survival after transcatheter aortic valve
      replacement in older adults with severe aortic stenosis: a single-center
      experience.
AB  - OBJECTIVES: This study sought to evaluate the impact of frailty in older adults
      undergoing transcatheter aortic valve replacement (TAVR) for symptomatic aortic
      stenosis. BACKGROUND: Frailty status impacts prognosis in older adults with heart
      disease; however, the impact of frailty on prognosis after TAVR is unknown.
      METHODS: Gait speed, grip strength, serum albumin, and activities of daily living
      status were collected at baseline and used to derive a frailty score among
      patients who underwent TAVR procedures at a single large-volume institution. The
      cohort was dichotomized on the basis of median frailty score into frail and not
      frail groups. The impact of frailty on procedural outcomes (stroke, bleeding,
      vascular complications, acute kidney injury, and mortality at 30 days) and 1-year
      mortality was evaluated. RESULTS: Frailty status was assessed in 159 subjects who
      underwent TAVR (age 86 +/- 8 years, Society of Thoracic Surgery Risk Score 12 +/-
      4). Baseline frailty score was not associated with conventionally ascertained
      clinical variables or Society of Thoracic Surgery score. Although high frailty
      score was associated with a longer post-TAVR hospital stay when compared with
      lower frailty score (9 +/- 6 days vs. 6 +/- 5 days, respectively, p = 0.004),
      there were no significant crude associations between frailty status and
      procedural outcomes, suggesting adequacy of the standard selection process for
      identifying patients at risk for periprocedural complications after TAVR. Frailty
      status was independently associated with increased 1-year mortality (hazard
      ratio: 3.5, 95% confidence interval: 1.4 to 8.5, p = 0.007) after TAVR.
      CONCLUSIONS: Frailty was not associated with increased periprocedural
      complications in patients selected as candidates to undergo TAVR but was
      associated with increased 1-year mortality after TAVR. Further studies will
      evaluate the independent value of this frailty composite in older adults with
      aortic stenosis.

PMID- 22995887
TI  - Conformational pulsatile changes of the aortic annulus: impact on prosthesis
      sizing by computed tomography for transcatheter aortic valve replacement.
AB  - OBJECTIVES: This study sought to investigate pulsatile changes of the aortic
      annulus and their impact on prosthesis selection by computed tomography (CT).
      BACKGROUND: Precise noninvasive prosthesis sizing is a prerequisite for
      transcatheter aortic valve replacement. METHODS: A total of 110 patients with
      severe aortic stenosis (mean age: 82.9 +/- 8 years, mean aortic valve area: 0.69
      +/- 0.18 cm(2)) underwent electrocardiogram-gated CT. Aortic annulus dimensions
      were planimetrically quantified as area-derived diameter (D(A) = 2 *?(CSA/pi),
      where CSA is the cross-sectional area) and perimeter-derived diameter (D(P) =
      P/pi, where P is the length of the perimeter) in 5% increments of the RR
      interval. Hypothetical prosthesis sizing was based on D(A) and D(P) (23-mm
      prosthesis for <22 mm; 26 mm: 22 to 25 mm; 29 mm: >25 mm) and compared between
      maximum and traditional cardiac CT reconstruction phases at 35% and 75% of RR.
      Agreement for prosthesis selection was calculated by kappa statistics. RESULTS:
      D(A) and D(P) were increased and eccentricity was reduced during systole, with
      D(A-MAX) and D(P-MAX) most often observed at 20% of RR. D(P) was consistently
      larger than D(A). Average net differences were 2.0 +/- 0.6 mm and 1.7 +/- 0.5 mm
      by D(A-MIN) versus D(A-MAX) and D(P-MIN) versus D(P-MAX). Agreement for
      prosthesis sizing was found in 93 of 110 patients (kappa = 0.75) by D(A-75%) and
      in 80 of 110 patients (kappa = 0.53) by D(A-MAX) compared with D(A-35%); and in
      94 of 110 patients (kappa = 0.73) by D(P-75%) and in 93 of 110 patients (kappa =
      0.73) by D(P-MAX) compared with D(P-35%). With sizing by D(A-75%) or D(P-75%),
      nominal prosthesis diameter was smaller than D(A-MAX) or D(P-MAX) in 15 and 6
      patients respectively. CONCLUSIONS: Aortic annulus morphology exhibits
      conformational pulsatile changes throughout the cardiac cycle due to deformation
      and stretch. These changes affect prosthesis selection. Prosthesis selection by
      diastolic perimeter- or area-derived dimensions harbors the risk of undersizing.

PMID- 22995888
TI  - Multiple interstrut cavities: a potential mechanism for very late stent
      thrombosis? Insights from optical coherence tomography.

PMID- 22995889
TI  - Embolotherapy in giant pulmonary arteriovenous malformations: blocking the exit
      reducing the risk of peri-interventional stroke?

PMID- 22995891
TI  - Anomalous origin of the left internal mammary artery from the aortic arch.

PMID- 22995892
TI  - The sweet taste of success: the presence of glucose in the oral cavity moderates
      the depletion of self-control resources.
AB  - According to the resource-depletion model, self-control is a limited resource
      that is depleted after a period of exertion. Evidence consistent with this model
      indicates that self-control relies on glucose metabolism and glucose
      supplementation to depleted individuals replenishes self-control resources. In
      five experiments, we tested an alternative hypothesis that glucose in the oral
      cavity counteracts the deleterious effects of self-control depletion. We
      predicted a glucose mouth rinse, as opposed to an artificially sweetened placebo
      rinse, would lead to better self-control after depletion. In Studies 1 to 3,
      participants engaging in a depleting task performed significantly better on a
      subsequent self-control task after receiving a glucose mouth rinse, as opposed to
      participants rinsing with a placebo. Studies 4 and 5 replicated these findings
      and demonstrated that the glucose mouth rinse had no effect on self-control in
      nondepleted participants. Results are consistent with a neural rather than
      metabolic mechanism for the effect of glucose supplementation on self-control.

PMID- 22995893
TI  - Living dangerously on borrowed time during slow, unrecognized regime shifts.
AB  - Regime shifts from one ecological state to another are often portrayed as sudden,
      dramatic, and difficult to reverse. Yet many regime shifts unfold slowly and
      imperceptibly after a tipping point has been exceeded, especially at regional and
      global scales. These long, smooth transitions between equilibrium states are easy
      to miss, ignore, or deny, confounding management and governance. However, slow
      responses by ecosystems after transgressing a dangerous threshold also affords
      borrowed time - a window of opportunity to return to safer conditions before the
      new state eventually locks in and equilibrates. In this context, the most
      important challenge is a social one: convincing enough people to confront
      business-as-usual before time runs out to reverse unwanted regime shifts even
      after they have already begun.

PMID- 22995894
TI  - Trait-mediated trophic interactions: is foraging theory keeping up?
AB  - Many ecologists believe that there is a lack of foraging theory that works in
      community contexts, for populations of unique individuals each making trade-offs
      between food and risk that are subject to feedbacks from behavior of others. Such
      theory is necessary to reproduce the trait-mediated trophic interactions now
      recognized as widespread and strong. Game theory can address feedbacks but does
      not provide foraging theory for unique individuals in variable environments.
      'State- and prediction-based theory' (SPT) is a new approach that combines
      existing trade-off methods with routine updating: individuals regularly predict
      future food availability and risk from current conditions to optimize a fitness
      measure. SPT can reproduce a variety of realistic foraging behaviors and trait
      mediated trophic interactions with feedbacks, even when the environment is
      unpredictable.

PMID- 22995895
TI  - Conflictual speciation: species formation via genomic conflict.
AB  - A remarkable suite of forms of genomic conflict has recently been implicated in
      speciation. We propose that these diverse roles of genomic conflict in speciation
      processes can be unified using the concept of 'conflictual speciation'.
      Conflictual speciation centers on the evolution of reproductive isolation as a
      byproduct of antagonistic selection among genomic elements with divergent fitness
      interests. Intragenomic conflicts are expected to readily generate Dobzhansky
      Muller incompatibilities, due to population-specific interactions between
      opposing elements, and thus they could be especially important in speciation.
      Moreover, selection from genomic conflicts should be relatively unrelenting
      across ecological and evolutionary time scales. We explain how intragenomic
      conflicts can promote, or sometimes constrain, speciation, and describe evidence
      relating conflicts to the evolution of reproductive isolation.

PMID- 22995896
TI  - Introduced parasites in food webs: new species, shifting structures?
AB  - Introduction of free-living species also results in co-introduction of their
      parasites. Since recent advances have shown that native parasites dramatically
      alter food web structure, I evaluate here how introduced parasites might
      reorganise food webs. Empirical evidence suggests that introduced parasites alter
      food webs qualitatively through topological changes and quantitatively through
      shifts in trophic relationships arising from modified host phenotypic traits. I
      argue that predicting the extent of food web reorganisation is, however,
      difficult due to underlying ecological and evolutionary processes that could
      provide contrasting food web outcomes, including enemy release, biotic
      resistance, and parasite spillover and spillback. Nevertheless, I suggest these
      food web reorganisations represent a further aspect of human-mediated global
      change resulting in irreversible consequences across multiple trophic levels.

PMID- 22995897
TI  - How many dendritic cells are required to initiate a T-cell response?
AB  - T-cell activation in lymph nodes relies on encounters with antigen (Ag)-bearing
      dendritic cells (DCs) but the number of DCs required to initiate an immune
      response is unknown. Here we have used a combination of flow cytometry, 2-photon
      imaging, and computational modeling to quantify the probability of T cell-DC
      encounters. We calculated that the chance for a T cell residing 24 hours in a
      murine popliteal lymph nodes to interact with a DC was 8%, 58%, and 99% in the
      presence of 10, 100, and 1000 Ag-bearing DCs, respectively. Our results reveal
      the existence of a threshold in DC numbers below which T-cell responses fail to
      be elicited for probabilistic reasons. In mice and probably humans, we estimate
      that a minimum of 85 DCs are required to initiate a T-cell response when starting
      from precursor frequency of 10(-6). Our results have implications for the
      rational design of DC-based vaccines.

PMID- 22995898
TI  - NPP4 is a procoagulant enzyme on the surface of vascular endothelium.
AB  - Ap3A is a platelet-dense granule component released into the extracellular space
      during the second wave of platelet aggregation on activation. Here, we identify
      an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4),
      as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and
      secretion. We demonstrate that NPP4 is present on the surface of vascular
      endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and
      ATP. Platelet aggregation assays with citrated platelet-rich plasma reveal that
      the primary and secondary waves of aggregation and dense granule release are
      strongly induced by nanomolar NPP4 in a concentration-dependent manner in the
      presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation
      followed by rapid disaggregation. NPP2 and an active site NPP4 mutant, neither of
      which appreciably hydrolyzes Ap3A, have no effect on platelet aggregation and
      secretion. Finally, by using ADP receptor blockade we confirm that NPP4 mediates
      platelet aggregation via release of ADP from Ap3A and activation of ADP
      receptors. Collectively, these studies define the biologic and enzymatic basis
      for NPP4 and Ap3A activity in platelet aggregation in vitro and suggest that NPP4
      promotes hemostasis in vivo by augmenting ADP-mediated platelet aggregation at
      the site of vascular injury.

PMID- 22995899
TI  - Meis1 regulates the metabolic phenotype and oxidant defense of hematopoietic stem
      cells.
AB  - The role of Meis1 in leukemia is well established, but its role in hematopoietic
      stem cells (HSCs) remains poorly understood. Previously, we showed that HSCs use
      glycolytic metabolism to meet their energy demands. However, the mechanism of
      regulation of HSC metabolism, and the importance of maintaining this distinct
      metabolic phenotype on HSC function has not been determined. More importantly,
      the primary function of Meis1 in HSCs remains unknown. Here, we examined the
      effect of loss of Meis1 on HSC function and metabolism. Inducible Meis1 deletion
      in adult mouse HSCs resulted in loss of HSC quiescence, and failure of bone
      marrow repopulation after transplantation. While we previously showed that Meis1
      regulates Hif-1alpha transcription in vitro, we demonstrate here that loss of
      Meis1 results in down-regulation of both Hif-1alpha and Hif-2alpha in HSCs. This
      resulted in a shift to mitochondrial metabolism, increased reactive oxygen
      species production, and apoptosis of HSCs. Finally, we demonstrate that the
      effect of Meis1 knockout on HSCs is entirely mediated through reactive oxygen
      species where treatment of the Meis1 knockout mice with the scavenger N
      acetylcystein restored HSC quiescence and rescued HSC function. These results
      uncover an important transcriptional network that regulates metabolism, oxidant
      defense, and maintenance of HSCs.

PMID- 22995900
TI  - Dynamic clonal analysis of murine hematopoietic stem and progenitor cells marked
      by 5 fluorescent proteins using confocal and multiphoton microscopy.
AB  - We demonstrate a methodology for tracing the clonal history of hematopoietic stem
      and progenitor cells (HSPCs) behavior in live tissues in 4 dimensions (4D). This
      integrates genetic combinatorial marking using lentiviral vectors encoding
      various fluorescent proteins (FPs) with advanced imaging methods. Five FPs:
      Cerulean, EGFP, Venus, tdTomato, and mCherry were concurrently used to create a
      diverse palette of color-marked cells. A key advantage of imaging using a
      confocal/2-photon hybrid microscopy approach is the simultaneous assessment of
      uniquely 5FP-marked cells in conjunction with structural components of the
      tissues at high resolution. Volumetric analyses revealed that spectrally coded
      HSPC-derived cells can be detected noninvasively in various intact tissues,
      including the bone marrow, for extensive periods of time after transplantation.
      Live studies combining video-rate multiphoton and confocal imaging in 4D
      demonstrate the possibility of dynamic cellular and clonal tracking in a
      quantitative manner. This methodology has applications in the understanding of
      clonal architecture in normal and perturbed hematopoiesis.

PMID- 22995901
TI  - Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid
      cancer cell line.
AB  - INTRODUCTION: Patients with metastatic thyroid cancers that do not uptake iodine
      need effective therapeutic option. Differentiation-inducing agents have been
      tried to restore functional expression of sodium iodide symporter (NIS) without
      success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known
      as potential antioxidant, on expression of sodium iodide symporter in thyroid
      cancer cells. METHODS: Human thyroid cancer-derived cell lines, TPC-1, were
      treated with ALA, and changes in NIS mRNA and protein expression were measured.
      ALA's effect on NIS gene promoter was evaluated, and functional NIS expression
      was assessed by iodide uptake assay. RESULTS: Treatment with ALA increased NIS
      mRNA expression up to ten folds of control dose-dependently after 24 h of
      exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6
      fold. ALA induced expression of NIS protein, but had no significant effect on the
      plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear
      translocation of pCREB, and co-treatment of ALA and trichostatin A increased
      iodide uptake by three folds in TPC-1 cells. CONCLUSIONS: ALA is a potential
      agent to increase NIS transcription in TPC-1. It could be used as an adjunctive
      agent to increase efficacy of radioiodine therapy if combined with a strategy to
      increase NIS protein trafficking to cell membrane.

PMID- 22995902
TI  - Be spoilt for choice with radiolabelled RGD peptides: preclinical evaluation of
      68Ga-TRAP(RGD)3.
AB  - Gallium-68 is rapidly gaining importance, as this generator-produced PET isotope
      is available independent of on-site cyclotrons, enabling radiopharmaceutical
      production with comparably simple techniques at low cost. The recently introduced
      TRAP chelator combines the advantage of straightforward design of multimeric 68Ga
      radiopharmaceuticals with very fast and efficient 68Ga-labeling. We synthesized a
      series of five cyclo(RGDfK) peptide trimers and determined their alpha(v)beta3
      integrin affinities in competition assays on alpha(v)beta3-expressing M21 human
      melanoma cells against 125I-echistatin. The compound with highest IC50, Ga
      TRAP(RGD)3, showed more than 7-fold higher affinity compared to the monomers F
      Galacto-RGD and Ga-NODAGA-c(RGDyK). TRAP(RGD)3 was radiolabeled with 68Ga in a
      fully automated GMP compliant manner. CD-1 athymic nude mice bearing M21/M21L
      human melanoma xenografts were used for biodistribution studies, blockade
      experiments, metabolite studies and PET imaging. 68Ga-TRAP(RGD)3 exhibited high
      M21 tumor uptake (6.08+/-0.63% ID/g, 60 min p.i.), was found to be fully stable
      in vivo, and showed a fast renal clearance. Blockade studies showed that uptake
      in the tumor, as well as in all other tissues, is highly integrin specific. A
      comparison of biodistribution and PET data of 68Ga-TRAP(RGD)3 with those of 68Ga
      NODAGA-c(RGDyK) and 18F-Galacto-RGD showed that the higher affinity of the trimer
      effects a larger dynamic response of tracer uptake to integrin expression, i.e.,
      enhanced integrin-specific uptake in all tissues. We conclude that 68Ga
      TRAP(RGD)3 could allow for imaging of low-level integrin expression in tissues
      which are not visible with the two competitors. Overall, the study constitutes
      proof of concept for the favourable in vivo properties of TRAP-based 68Ga
      radiopharmaceuticals.

PMID- 22995903
TI  - Are there risk factors for acute renal failure in adult patients using
      deoxycholate amphotericin B?
AB  - BACKGROUND: Deoxycholate amphotericin B (DAB) is a nephrotoxic drug and the
      incidence of acute kidney injury (AKI) is high. AIMS: The aim of this study was
      to describe the incidence of AKI in patients under DAB therapy and determine risk
      factor to predict the AKI. METHODS: The data of this retrospective study included
      previously hospitalized patients treated with intravenous DAB for at least five
      days. Clinical and laboratorial data were evaluated and AKI was classified in
      stages using Acute Kidney Injury Network criteria. Univariated test followed by a
      multivariable analysis was performed to determine risk factor and Kaplan-Meier
      survival estimates were calculated to evaluate the role of AKI in the outcome.
      RESULTS: One hundred six patients were included in the final analysis. AKI
      occurred in 51.9% and dialysis was necessary in 4.7%. The occurrence of AKI was
      not associated with any risk factor. The mortality of the patients was neither
      associated with AKI nor with dialysis. Other nephrotoxic drugs were not risk
      factors for AKI. CONCLUSIONS: The incidence of AKI in patients using DAB is high
      and we cannot predict the chance of AKI using clinical or laboratorial data.

PMID- 22995904
TI  - Association between underweight and overweight/obesity with oral health among
      independently living Brazilian elderly.
AB  - OBJECTIVE: Poor oral status, represented by partial/complete tooth loss, may lead
      to changes in food choice, which may ultimately lead to underweight, overweight,
      or obesity. The aim of this study is to evaluate whether poor oral status is
      associated with underweight or overweight/obesity, regardless of physical
      activity. METHODS: This cross-sectional study is part of a major project, The
      Frailty in Brazilian Elderly Study, carried out in Campinas, Brazil (2008-2009).
      The sample was composed of 900 independent-living older adults. Complete data
      were available for 875 individuals including sociodemographic, self-reported
      amount of medications used and eating difficulty questionnaire, smoking habit,
      depressive symptoms, physical activity, oral examination, and anthropometric
      assessments according to the WHO criteria. Body mass index was used as an
      outcome. Multinomial logistic regression was adjusted for confounding variables.
      RESULTS: The mean age of the sample was 72.7 y (+/- 5.81) and the prevalence of
      edentulism was 47.7%. Edentate individuals not wearing dentures were more likely
      to be underweight [odds ratio (OR) = 3.94, 95% confidence interval (CI) 1.14
      13.64] and overweight/obese (OR = 2.88, 95%CI 1.12-7.40). Males (OR = 0.56, 95%CI
      0.36-0.85) and those not using medications (OR = 0.41 95%CI 0.24-0.70) were less
      likely to be overweight/obese. Individuals who smoke (OR = 2.62, 95%CI 1.26-5.44)
      were more likely to be underweight. Older individuals with family income between
      3.1 and 5 minimum wage (OR = 1.69, 95%CI 1.00-2.87) were more likely to be
      overweight/obese. CONCLUSION: To our knowledge, this is one of the first studies
      associating poor oral health, represented by edentulism not rehabilitated with
      dentures, with unfavorable body mass, regardless of the two major confounders,
      physical activity and depression symptoms.

PMID- 22995905
TI  - Pharmaconutrition with antioxidant micronutrients in the critically ill: the time
      has come!

PMID- 22995906
TI  - Probing the interaction of SR141716A with the CB1 receptor.
AB  - SR141716A binds selectively to the brain cannabinoid (CB1) receptor and exhibits
      a potent inverse agonist/antagonist activity. Although SR141716A, also known as
      rimonabant, has been withdrawn from the market due to severe side effects, there
      remains interest in some of its many potential medical applications.
      Consequently, it is imperative to understand the mechanism by which SR141716A
      exerts its inverse agonist activity. As a result of using an approach combining
      mutagenesis and molecular dynamics simulations, we determined the binding mode of
      SR141716A. We found from the simulation of the CB1-SR141716A complex that
      SR141716A projects toward TM5 to interact tightly with the major binding pocket,
      replacing the coordinated water molecules, and secures the Trp-356(6.48)
      rotameric switch in the inactive state to promote the formation of an extensive
      water-mediated H-bonding network to the highly conserved SLAXAD and NPXXY motifs
      in TM2/TM7. We identify for the first time the involvement of the minor binding
      pocket formed by TM2/TM3/TM7 for SR141716A binding, which complements the major
      binding pocket formed by TM3/TM5/TM6. Simulation of the F174(2.61)A mutant CB1
      SR141716A complex demonstrates the perturbation of TM2 that attenuates SR141716A
      binding indirectly. These results suggest SR141716A exerts inverse agonist
      activity through the stabilization of both TM2 and TM5, securing the Trp
      356(6.48) rotameric switch and restraining it from activation.

PMID- 22995908
TI  - The importance of TM3-4 loop subdomains for functional reconstitution of glycine
      receptors by independent domains.
AB  - Truncated glycine receptors that have been found in human patients suffering from
      the neuromotor disorder hyperekplexia or in spontaneous mouse models resulted in
      non-functional ion channels. Rescue of function experiments with the lacking
      protein portion expressed as a separate independent domain demonstrated
      restoration of glycine receptor functionality in vitro. This construct harbored
      most of the TM3-4 loop, TM4, and the C terminus and was required for concomitant
      transport of the truncated alpha1 and the complementation domain from the
      endoplasmic reticulum toward the cell surface, thereby enabling complex formation
      of functional glycine receptors. Here, the complementation domain was stepwise
      truncated from its N terminus in the TM3-4 loop. Truncation of more than 49 amino
      acids led again to loss of functionality in the receptor complex expressed from
      two independent domain constructs. We identified residues 357-418 in the
      intracellular TM3-4 loop as being required for reconstitution of functional
      glycine-gated channels. All complementation constructs showed cell surface
      protein expression and correct orientation according to glycine receptor
      topology. Moreover, we demonstrated that the truncations did not result in a
      decreased protein-protein interaction between both glycine receptor domains.
      Rather, deletions of more than 49 amino acids abolished conformational changes
      necessary for ion channel opening. When the TM3-4 loop subdomain harboring
      residues 357-418 was expressed as a third independent construct together with the
      truncated N-terminal and C-terminal glycine receptor domains, functionality of
      the glycine receptor was again restored. Thus, residues 357-418 represent an
      important determinant in the process of conformational rearrangements following
      ligand binding resulting in channel opening.

PMID- 22995907
TI  - Degradation of an old human protein: age-dependent cleavage of gammaS-crystallin
      generates a peptide that binds to cell membranes.
AB  - Long-lived proteins exist in a number of tissues in the human body; however,
      little is known about the reactions involved in their degradation over time. Lens
      proteins, which do not turn over, provide a useful system to examine such
      processes. Using a combination of Western blotting and proteomic methodology, age
      related changes to a major protein, gammaS-crystallin, were studied. By teenage
      years, insoluble intact gammaS-crystallin was detected, indicative of protein
      denaturation. This was not the only change, however, because blots revealed
      evidence of significant cross-linking as well as cleavage of gammaS-crystallin in
      all adult lenses. Cleavage at a serine residue near the C terminus was a major
      reaction that caused the release of a 12-residue peptide, SPAVQSFRRIVE, which
      bound tightly to lens cell membranes. Several other crystallin-derived peptides
      with double basic residues also lodged in the cell membrane fraction. Model
      studies showed that once cleaved from gammaS-crystallin, SPAVQSFRRIVE adopts a
      markedly different shape from that in the intact protein. Further, the acquired
      helical conformation may explain why the peptide seems to affect water
      permeability. This observation may help explain the changes to cell membranes
      known to be associated with aging in human lenses. Age-related cleavage of long
      lived proteins may therefore yield peptides with untoward biological activity.

PMID- 22995909
TI  - Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)
      mediated correction of alpha1-antitrypsin deficiency.
AB  - alpha1-Antitrypsin (alpha1AT) deficiency (alpha1ATD) is a consequence of
      defective folding, trafficking, and secretion of alpha1AT in response to a defect
      in its interaction with the endoplasmic reticulum proteostasis machineries. The
      most common and severe form of alpha1ATD is caused by the Z-variant and is
      characterized by the accumulation of alpha1AT polymers in the endoplasmic
      reticulum of the liver leading to a severe reduction (>85%) of alpha1AT in the
      serum and its anti-protease activity in the lung. In this organ alpha1AT is
      critical for ensuring tissue integrity by inhibiting neutrophil elastase, a
      protease that degrades elastin. Given the limited therapeutic options in
      alpha1ATD, a more detailed understanding of the folding and trafficking biology
      governing alpha1AT biogenesis and its response to small molecule regulators is
      required. Herein we report the correction of Z-alpha1AT secretion in response to
      treatment with the histone deacetylase (HDAC) inhibitor suberoylanilide
      hydroxamic acid (SAHA), acting in part through HDAC7 silencing and involving a
      calnexin-sensitive mechanism. SAHA-mediated correction restores Z-alpha1AT
      secretion and serpin activity to a level 50% that observed for wild-type
      alpha1AT. These data suggest that HDAC activity can influence Z-alpha1AT protein
      traffic and that SAHA may represent a potential therapeutic approach for
      alpha1ATD and other protein misfolding diseases.

PMID- 22995911
TI  - Human and mouse type I natural killer T cell antigen receptors exhibit different
      fine specificities for CD1d-antigen complex.
AB  - Human and mouse type I natural killer T (NKT) cells respond to a variety of CD1d
      restricted glycolipid antigens (Ags), with their NKT cell antigen receptors (NKT
      TCRs) exhibiting reciprocal cross-species reactivity that is underpinned by a
      conserved NKT TCR-CD1d-Ag docking mode. Within this common docking footprint, the
      NKT TCR recognizes, to varying degrees of affinity, a range of Ags. Presently, it
      is unclear whether the human NKT TCRs will mirror the generalities underpinning
      the fine specificity of the mouse NKT TCR-CD1d-Ag interaction. Here, we assessed
      human NKT TCR recognition against altered glycolipid ligands of alpha
      galactosylceramide (alpha-GalCer) and have determined the structures of a human
      NKT TCR in complex with CD1d-4',4"-deoxy-alpha-GalCer and CD1d-alpha-GalCer with
      a shorter, di-unsaturated acyl chain (C20:2). Altered glycolipid ligands with
      acyl chain modifications did not affect the affinity of the human NKT TCR-CD1d-Ag
      interaction. Surprisingly, human NKT TCR recognition is more tolerant to
      modifications at the 4'-OH position in comparison with the 3'-OH position of
      alpha-GalCer, which contrasts the fine specificity of the mouse NKT TCR-CD1d-Ag
      recognition (4'-OH > 3'-OH). The fine specificity differences between human and
      mouse NKT TCRs was attributable to differing interactions between the respective
      complementarity-determining region 1alpha loops and the Ag. Accordingly, germline
      encoded fine-specificity differences underpin human and mouse type I NKT TCR
      interactions, which is an important consideration for therapeutic development and
      NKT cell physiology.

PMID- 22995910
TI  - The crystal structure of the lipid II-degrading bacteriocin syringacin M suggests
      unexpected evolutionary relationships between colicin M-like bacteriocins.
AB  - Colicin-like bacteriocins show potential as next generation antibiotics with
      clinical and agricultural applications. Key to these potential applications is
      their high potency and species specificity that enables a single pathogenic
      species to be targeted with minimal disturbance of the wider microbial community.
      Here we present the structure and function of the colicin M-like bacteriocin,
      syringacin M from Pseudomonas syringae pv. tomato DC3000. Syringacin M kills
      susceptible cells through a highly specific phosphatase activity that targets
      lipid II, ultimately inhibiting peptidoglycan synthesis. Comparison of the
      structures of syringacin M and colicin M reveals that, in addition to the
      expected similarity between the homologous C-terminal catalytic domains, the
      receptor binding domains of these proteins, which share no discernible sequence
      homology, share a striking structural similarity. This indicates that the
      generation of the novel receptor binding and species specificities of these
      bacteriocins has been driven by diversifying selection rather than diversifying
      recombination as suggested previously. Additionally, the structure of syringacin
      M reveals the presence of an active site calcium ion that is coordinated by a
      conserved aspartic acid side chain and is essential for catalytic activity. We
      show that mutation of this residue to alanine inactivates syringacin M and that
      the metal ion is absent from the structure of the mutant protein. Consistent with
      the presence of Ca(2+) in the active site, we show that syringacin M activity is
      supported by Ca(2+), along with Mg(2+) and Mn(2+), and the protein is
      catalytically inactive in the absence of these ions.

PMID- 22995912
TI  - Distant cytosolic residues mediate a two-way molecular switch that controls the
      modulation of inwardly rectifying potassium (Kir) channels by cholesterol and
      phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)).
AB  - BACKGROUND: Cholesterol modulates inwardly rectifying potassium (Kir) channels.
      RESULTS: A two-way molecular cytosolic switch controls channel modulation by
      cholesterol and PI(4,5)P(2). CONCLUSION: Cholesterol and PI(4,5)P(2) induce a
      common gating pathway of Kir2.1 despite their opposite impact on channel
      function. SIGNIFICANCE: These findings provide insights into structure-function
      relationship of ion channels and contribute to understanding of the mechanisms
      underlying their regulation by lipids. Inwardly rectifying potassium (Kir)
      channels play an important role in setting the resting membrane potential and
      modulating membrane excitability. An emerging feature of several Kir channels is
      that they are regulated by cholesterol. However, the mechanism by which
      cholesterol affects channel function is unclear. Here we show that mutations of
      two distant Kir2.1 cytosolic residues, Leu-222 and Asn-251, form a two-way
      molecular switch that controls channel modulation by cholesterol and affects
      critical hydrogen bonding. Notably, these two residues are linked by a residue
      chain that continues from Asn-251 to connect adjacent subunits. Furthermore, our
      data indicate that the same switch also regulates the sensitivity of the channels
      to phosphatidylinositol 4,5-bisphosphate, a phosphoinositide that is required for
      activation of Kir channels. Thus, although cholesterol and phosphatidylinositol
      4,5-bisphosphate do not interact with the same region of Kir2.1, these different
      modulators induce a common gating pathway of the channel.

PMID- 22995913
TI  - The TG-interacting factor TGIF1 regulates stress-induced proinflammatory
      phenotype of endothelial cells.
AB  - The endothelium contributes to the control of the tissue inflammatory response
      following stress and in particular after exposure to ionizing radiation. We
      previously showed that the TG-interacting factor 1 (TGIF1) plays a role in
      radiation-induced normal tissue injury. In this study we hypothesized that this
      protein could play a role in inflammation. The role of TGIF1 in the stress
      induced proinflammatory phenotype was investigated in human endothelial cells. In
      HUVECs ionizing radiation induces TGIF1 expression as well as a proinflammatory
      phenotype associated with up-regulation of IL-6, IL-8, CXCL1, MIP-2, and MCP-1.
      TGIF1 overexpression enhances the radiation-induced proinflammatory phenotype
      whereas TGIF1 silencing limits both the TNF-alpha- and radiation-induced
      overexpression of proinflammatory cytokines. Interestingly, in vivo, in radiation
      induced intestinal inflammation in mice, TGIF1 genetic deficiency is associated
      with a reduced radiation-induced overexpression of proinflammatory molecules. In
      HUVECs, TNF-alpha- and radiation-induced NF-kappaB pathway activation is not
      influenced by TGIF1 expression, whereas TGIF1 knockdown inhibits both TNF-alpha-
      and radiation-induced p38 MAPK pathway activation. This study demonstrates that
      TGIF1 plays a role in TNF-alpha- and radiation-induced inflammation and suggests
      that it could be a target in limiting this event in the vascular compartment.

PMID- 22995914
TI  - CXCL12/CXCR4 protein signaling axis induces sonic hedgehog expression in
      pancreatic cancer cells via extracellular regulated kinase- and Akt kinase
      mediated activation of nuclear factor kappaB: implications for bidirectional
      tumor-stromal interactions.
AB  - Recent evidence suggests a major role of tumor-stromal interactions in pancreatic
      cancer pathobiology. The chemokine CXCL12 (stromal cell-derived factor 1 (SDF
      1)), abundantly produced by stromal cells, promotes progression, metastasis, and
      chemoresistance of pancreatic cancer cells. On the other hand, pancreatic tumor
      cell-derived sonic hedgehog (SHH) acts predominantly on stromal cells to induce
      desmoplasia and, thus, has a paracrine effect on tumorigenesis and therapeutic
      outcome. In this study, we examined the association between these two proteins of
      pathological significance in pancreatic cancer. Our data demonstrate that CXCL12
      leads to a dose- and time-dependent up-regulation of SHH in pancreatic cancer
      cells. CXCL12-induced SHH up-regulation is specifically mediated through the
      receptor CXCR4 and is dependent on the activation of downstream Akt and ERK
      signaling pathways. Both Akt and ERK cooperatively promote nuclear accumulation
      of NF-kappaB by inducing the phosphorylation and destabilization of its
      inhibitory protein, IkappaB-alpha. Using dominant negative IkappaB-alpha, a SHH
      promoter (deletion mutant) reporter, and chromatin immunoprecipitation assays, we
      demonstrate that CXCL12 exposure enhances direct binding of NF-kappaB to the SHH
      promoter and that suppression of NF-kappaB activation abrogates CXCL12-induced
      SHH expression. Finally, our data demonstrate a strong correlative expression of
      CXCR4 and SHH in human pancreatic cancer tissues, whereas their expression is not
      observed in the normal pancreas. Altogether, our data reveal a novel mechanism
      underlying aberrant SHH expression in pancreatic cancer and identify a molecular
      link facilitating bidirectional tumor-stromal interactions.

PMID- 22995915
TI  - Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial
      cell hyperplasia via proinflammatory and hedgehog signaling.
AB  - Disruption of mammary stromal-epithelial communication leads to aberrant mammary
      gland development and induces mammary tumorigenesis. Macrophages have been
      implicated in carcinogenesis primarily by creating an inflammatory
      microenvironment, which promotes growth of the adjacent epithelial cells.
      Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator,
      promotes macrophage inflammatory responsiveness by inducing NF-kappaB activity,
      which has been implicated in tumor cell growth and survival by aberrant sonic
      hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1
      overexpression results in precocious alveologenesis in the virgin AEBP1
      transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated
      in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression.
      Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT))
      mice resulted in alveolar hyperplasia with up-regulation of NF-kappaB activity
      and TNFalpha expression as displayed in the AEBP1(TG) mammary macrophages and
      epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7
      macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression
      was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells
      co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG)
      macrophage culture media promoted NF-kappaB activity and survival signal, Akt
      activation, in HC11 cells, whereas such effects were abolished by TNFalpha
      neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced
      proliferation in response to AEBP1(TG) macrophages and their conditioned media.
      Our findings highlight the role of AEBP1 in the signaling pathways regulating the
      cross-talk between mammary epithelium and stroma that could predispose the
      mammary tissue to tumorigenesis.

PMID- 22995919
TI  - Characterizing defects and transport in Si nanowire devices using Kelvin probe
      force microscopy.
AB  - Si nanowires (NWs) integrated in a field effect transistor device structure are
      characterized using scanning electron (SEM), atomic force, and scanning Kelvin
      probe force (KPFM) microscopy. Reactive ion etching (RIE) and vapor-liquid-solid
      (VLS) growth were used to fabricate NWs between predefined electrodes.
      Characterization of Si NWs identified defects and/or impurities that affect the
      surface electronic structure. RIE NWs have defects that both SEM and KPFM
      analysis associate with a surface contaminant as well as defects that have a
      voltage dependent response indicating impurity states in the energy bandgap. In
      the case of VLS NWs, even after aqua regia, Au impurity levels are found to
      induce impurity states in the bandgap. KPFM data, when normalized to the oxide
      capacitance response, also identify a subset of VLS NWs with poor electrical
      contact due to nanogaps and short circuits when NWs cross that is not observed in
      AFM images or in current-voltage measurements when NWs are connected in parallel
      across electrodes. The experiments and analysis presented outline a systematic
      method for characterizing a broad array of nanoscale systems under device
      operation conditions.

PMID- 22995916
TI  - Yeast ribosomal protein L40 assembles late into precursor 60 S ribosomes and is
      required for their cytoplasmic maturation.
AB  - Most ribosomal proteins play important roles in ribosome biogenesis and function.
      Here, we have examined the contribution of the essential ribosomal protein L40 in
      these processes in the yeast Saccharomyces cerevisiae. Deletion of either the
      RPL40A or RPL40B gene and in vivo depletion of L40 impair 60 S ribosomal subunit
      biogenesis. Polysome profile analyses reveal the accumulation of half-mers and a
      moderate reduction in free 60 S ribosomal subunits. Pulse-chase, Northern
      blotting, and primer extension analyses in the L40-depleted strain clearly
      indicate that L40 is not strictly required for the precursor rRNA (pre-rRNA)
      processing reactions but contributes to optimal 27 SB pre-rRNA maturation.
      Moreover, depletion of L40 hinders the nucleo-cytoplasmic export of pre-60 S
      ribosomal particles. Importantly, all these defects most likely appear as the
      direct consequence of impaired Nmd3 and Rlp24 release from cytoplasmic pre-60 S
      ribosomal subunits and their inefficient recycling back into the nucle(ol)us. In
      agreement, we show that hemagglutinin epitope-tagged L40A assembles in the
      cytoplasm into almost mature pre-60 S ribosomal particles. Finally, we have
      identified that the hemagglutinin epitope-tagged L40A confers resistance to
      sordarin, a translation inhibitor that impairs the function of eukaryotic
      elongation factor 2, whereas the rpl40a and rpl40b null mutants are
      hypersensitive to this antibiotic. We conclude that L40 is assembled at a very
      late stage into pre-60 S ribosomal subunits and that its incorporation into 60 S
      ribosomal subunits is a prerequisite for subunit joining and may ensure proper
      functioning of the translocation process.

PMID- 22995917
TI  - Fibroblast growth factor (FGF) signaling during gastrulation negatively modulates
      the abundance of microRNAs that regulate proteins required for cell migration and
      embryo patterning.
AB  - FGF signaling plays a pivotal role in regulating cell movements and lineage
      induction during gastrulation. Here we identify 44 microRNAs that are expressed
      in the primitive streak region of gastrula stage chicken embryos. We show that
      the primary effect of FGF signaling on microRNA abundance is to negatively
      regulate the levels of miR-let-7b, -9, -19b, -107, -130b, and -218. LIN28B
      inhibits microRNA processing and is positively regulated by FGF signaling. Gain-
      and loss-of-function experiments show that LIN28B negatively regulates the
      expression of miR-19b, -130b, and let-7b, whereas negative modulation of miR-9, 
      107, and -218 appears to be independent of LIN28B function. Predicted mRNA
      targets of the FGF-regulated microRNAs are over-represented in serine/threonine
      and tyrosine kinase receptors, including ACVR1, ACVR2B, PDGFRA, TGFBR1, and
      TGFBR3. Luciferase assays show that these and other candidates are targeted by
      FGF-regulated microRNAs. PDGFRA, a receptor whose activity is required for cell
      migration through the primitive streak, is a target of miR-130b and -218 in vivo.
      These results identify a novel mechanism by which FGF signaling regulates gene
      expression by negatively modulating microRNA abundance through both LIN28B
      dependent and LIN28B-independent pathways.

PMID- 22995920
TI  - Persistent complete response after single-agent sunitinib treatment in a case of
      TFE translocation positive relapsed metastatic pediatric renal cell carcinoma.
AB  - Forty percent of renal cell carcinomas (RCCs) in childhood are characterized by
      translocation involving transcription factor E3 (TFE3) family members. Here, we
      describe a case of TFE3-positive RCC in which metastatic relapse to the
      mediastinal lymph nodes and pulmonary nodules was treated with single-agent
      sunitinib, a multitargeted tyrosine inhibitor. Complete radiologic remission was
      achieved after only 3 courses of treatment, and surgical exploration of
      metastases failed to identify any residual viable disease. The published
      experience of sunitinib in TFE-RCC is limited, and prospective evaluation of its
      activity in a larger number of patients is warranted.

PMID- 22995918
TI  - Impaired autophagy and delayed autophagic clearance of transforming growth factor
      beta-induced protein (TGFBI) in granular corneal dystrophy type 2.
AB  - Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease
      characterized by a progressive age-dependent extracellular accumulation of
      transforming growth factor beta-induced protein (TGFBI). Corneal fibroblasts from
      GCD2 patients also have progressive degenerative features, but the mechanism
      underlying this degeneration remains unknown. Here we observed that TGFBI was
      degraded by autophagy, but not by the ubiquitin/proteasome-dependent pathway. We
      also found that GCD2 homozygous corneal fibroblasts displayed a greater number of
      fragmented mitochondria. Most notably, mutant TGFBI (mut-TGFBI) extensively
      colocalized with microtubule-associated protein 1 light chain 3beta (MAP1LC3B,
      hereafter referred to as LC3)-enriched cytosolic vesicles and CTSD in primary
      cultured GCD2 corneal fibroblasts. Levels of LC3-II, a marker of autophagy
      activation, were significantly increased in GCD2 corneal fibroblasts.
      Nevertheless, levels of SQSTM1/p62 and of polyubiquitinated protein were also
      significantly increased in GCD2 corneal fibroblasts compared with wild-type (WT)
      cells. However, LC3-II levels did not differ significantly between WT and GCD2
      cells, as assessed by the presence of bafilomycin A 1, the fusion blocker of
      autophagosomes and lysosomes. Likewise, bafilomycin A 1 caused a similar change
      in levels of SQSTM1. Thus, the increase in autophagosomes containing mut-TGFBI
      may be due to inefficient fusion between autophagosomes and lysosomes. Rapamycin,
      an autophagy activator, decreased mut-TGFBI, whereas inhibition of autophagy
      increased active caspase-3, poly (ADP-ribose) polymerase 1 (PARP1) and reduced
      the viability of GCD2 corneal fibroblasts compared with WT controls. These data
      suggest that defective autophagy may play a critical role in the pathogenesis of
      GCD2.

PMID- 22995921
TI  - Life-threatening paraneoplastic syndrome in a child with sarcoma of the liver
      cured by emergency resection.
AB  - We believe this to be the first case of life-threatening paraneoplastic syndrome
      (PNS) in a child with undifferentiated embryonal sarcoma of the liver (UESL). We
      report a case of a 9-year-old child with UESL believed to be unresectable at
      presentation, who experienced life-threatening, refractory long QTc syndrome,
      Torsades de pointes, fevers of unknown origin, and secretory diarrhea
      necessitating emergency surgery. After failure of intravenous immunoglobulin and
      high-dose steroids to control PNS and despite pancytopenia from chemotherapy,
      very aggressive surgical resection was life saving and led to rapid resolution of
      PNS.

PMID- 22995922
TI  - Current practice managements regarding thromboembolic prophylaxis within the
      pediatric sarcoma patient population.
AB  - OBJECTIVE: Children with cancer are approximately 600 times more likely to
      develop thromboses than the general pediatric population. Current management
      strategies for children have been extrapolated from adult studies and prophylaxis
      guidelines remain controversial. The purpose of this study is to survey the
      current thromboembolic prophylaxis practice methods of physicians treating
      pediatric sarcoma patients. METHODS: Physicians involved in the care of sarcoma
      patients were surveyed using a 5-question survey designed to evaluate current
      clinical practices. RESULTS: Of 107 responding physicians, 67 identified
      themselves as involved in the treatment of pediatric sarcoma patients. The
      providers most likely to use any form of deep vein thrombosis prophylaxis were
      orthopedic surgeons (60%), followed by general surgeons (45%), pediatric
      oncologists (30%), and medical oncologists (25%). Of the providers polled, 48%
      use mechanical forms, 20% use chemical forms, and 31% use a combination.
      CONCLUSIONS: Currently, there is a lack of consensus regarding thromboembolic
      prophylaxis for pediatric sarcoma patients.

PMID- 22995923
TI  - Neonatal alloimmune neutropenia:  still a diagnostic and therapeutical challenge.
AB  - OBJECTIVE: To describe a case of neonatal alloimmune neutropenia (NAN), a very
      rare disease of the newborn and the first ever reported in our neonatal intensive
      care unit, with emphasis in its management and outcome. DESCRIPTION: We report a
      case of NAN due to anti-human neutrophil antigen-1b alloimmunization in a 29-week
      preterm admitted to our neonatal intensive care unit. In this case, the
      neutropenia was severe and persisted for almost 2 months. There was a good
      response to the administration of intravenous immunoglobulin. COMMENTS: NAN is
      caused by maternal production of neutrophil-specific alloantibodies in response
      to antigens from paternal heritage present on the newborn neutrophiles. The
      course of the disease is usually mild and self-limiting. The optimal therapy is
      yet a debate, with some authors finding the use of intravenous immunoglobulin
      effective, prophylactic antibiotic therapy or recombinant human granulocyte
      colony-stimulating factor.

PMID- 22995924
TI  - Cerebral toxoplasmosis after tandem high-dose chemotherapy and autologous
      hematopoietic cell transplant for neuroblastoma.
AB  - Toxoplasmosis is a well-recognized life-threatening complication of hematopoietic
      cell transplantation (HCT). This report describes a pediatric patient with stage
      4 neuroblastoma who developed cerebral toxoplasmosis after tandem high-dose
      chemotherapy with autologous HCT. Toxoplasmosis is rare in patients undergoing
      autologous HCT; however, tandem autologous HCT is more immunosuppressive than a
      single autologous HCT. Toxoplasmosis is a potential complication in autologous as
      well as allogeneic transplants, and should be considered in any post-HCT patient
      with neurological dysfunction. Rapid diagnosis and immediate antimicrobial
      treatment are crucial to avoid morbidity and mortality. Evaluation of toxoplasma
      serology should be standard in all patients undergoing tandem autologous HCT and
      seropositive patients should be started on appropriate prophylactic therapy.

PMID- 22995925
TI  - Osteosarcoma after bone marrow transplantation.
AB  - Three children treated with bone marrow transplantation for acute lymphoblastic
      leukemia, Diamond-Blackfan anemia, and congenital amegakaryocytic
      thrombocytopenia developed secondary osteosarcoma in the left tibia at the age of
      13, 13, and 9 years, respectively, at 51, 117, and 106 months after
      transplantation, respectively. Through treatment with chemotherapy and surgery,
      all 3 patients are alive without disease. We surveyed the literature and reviewed
      10 cases of osteosarcoma after hematopoietic stem cell transplantation (SCT),
      including our 3 cases. Eight of the patients had received myeloablative total
      body irradiation before SCT. The mean interval from SCT to the onset of
      osteosarcoma was 6 years and 4 months, and the mean age at the onset of
      osteosarcoma was 14 years and 5 months. The primary site of the post-SCT
      osteosarcoma was the tibia in 6 of 10 cases, in contrast to de novo osteosarcoma,
      in which the most common site is the femur. At least 7 of the 10 patients are
      alive without disease. Osteosarcoma should be one of the items for surveillance
      in the follow-up of patients who undergo SCT.

PMID- 22995926
TI  - Risk factor analysis of bloodstream infection in pediatric patients after
      hematopoietic stem cell transplantation.
AB  - Bloodstream infection (BSI) is a recognized cause of morbidity and mortality in
      children after hematopoietic stem cell transplantation (HSCT). However, there are
      limited reports on BSI after HSCT in pediatric patients in multiple centers. This
      study was a retrospective cohort analysis of consecutive patients who underwent
      allogeneic and autologous HSCT at the Department of Paediatrics, Hokkaido
      University Hospital, between 1988 and 2009; the Department of Paediatrics,
      Sapporo Hokuyu Hospital, between 2007 and 2009; and the Department of
      Paediatrics, Asahikawa Medical University, between 1989 and 2009. A total of 277
      patients underwent HSCT during the study period. In this multicenter analysis,
      cases of BSI after HSCT were recorded in the early posttransplant period (within
      the first 100 d), and BSI was observed in 24 of 277 HSCT patients. Multivariate
      analysis showed that nonmalignant disease was an independent factor associated
      with BSI after HSCT (hazard ratio 6.3 for aplastic anemia or Wiskott-Aldrich
      syndrome patients; confidence interval, 1.4-12.8; P = 0.012). We conclude that
      aplastic anemia and Wiskott-Aldrich syndrome were the novel risk factors for BSI
      in pediatric patients after HSCT.

PMID- 22995927
TI  - The association of anti-glutamic acid decarboxylase antibodies with different
      neurological findings in childhood.
AB  - Glutamic acid decarboxylase antibodies can rarely be associated with various
      neurological syndromes, which are usually present in adults. Here, we present 2
      affected children. Our first patient had a diagnosis of epilepsy and presented
      with continuous involuntary movements and multifocal myoclonic seizures following
      an infection at the age of 9 months. Anti-glutamic acid decarboxylase antibodies
      were found in the serum and cerebrospinal fluid. A partial response was obtained
      from intravenous immunoglobulin, steroid, and plasmapheresis treatment. The other
      patient presented with a clinical picture of acute cerebellar ataxia and mutism
      at the age of 6 years and recovered fully following intravenous immunoglobulin
      treatment. Neurological findings due to anti-glutamic acid decarboxylase
      antibodies may be more common in children than previously thought, and achieving
      an early diagnosis can be important for prompt treatment.

PMID- 22995928
TI  - On-line detection of root-induced volatiles in Brassica nigra plants infested
      with Delia radicum L. root fly larvae.
AB  - Plants emit various volatile organic compounds (VOCs) upon herbivore attack.
      These VOC emissions often show temporal dynamics which may influence the behavior
      of natural enemies using these volatiles as cues. This study analyzes on-line VOC
      emissions by roots of Brassica nigra plants under attack by cabbage root fly
      larvae, Delia radicum. Root emitted VOCs were detected using Proton-Transfer
      Reaction Mass Spectrometry (PTR-MS) and Gas Chromatography-Mass Spectrometry (GC
      MS). These analyses showed that several sulfur containing compounds, such as
      methanethiol, dimethyl sulfide (DMS), dimethyl disulfide (DMDS), dimethyl
      trisulfide (DMTS) and glucosinolate breakdown products, such as thiocyanates (TC)
      and isothiocyanates (ITC), were emitted by the roots in response to infestation.
      The emissions were subdivided into early responses, emerging within 1-6 h after
      infestation, and late responses, evolving only after 6-12 h. The marker for rapid
      responses was detected at m/z 60. The ion detected at m/z 60 was identified as
      thiocyanic acid, which is also a prominent fragment in some TC or ITC spectra.
      The emission of m/z 60 stopped when the larvae had pupated, which makes it an
      excellent indicator for actively feeding larvae. Methanethiol, DMS and DMDS
      levels increased much later in infested roots, indicating that activation of
      enzymes or genes involved in the production of these compounds may be required.
      Earlier studies have shown that both early and late responses can play a role in
      tritrophic interactions associated with Brassica species. Moreover, the
      identification of these root induced responses will help to design non-invasive
      analytical procedures to assess root infestations.

PMID- 22995929
TI  - Macroline-sarpagine and macroline-pleiocarpamine bisindole alkaloids from
      Alstonia angustifolia.
AB  - Nine bisindole alkaloids, comprising four belonging to the macroline-sarpagine
      group, and five belonging to the macroline-pleiocarpamine group, were isolated
      from the stem-bark extracts of Alstonia angustifolia (Apocynacea). Their
      structures were established using NMR and MS analyses.

PMID- 22995930
TI  - Ecotoxicity of manufactured ZnO nanoparticles--a review.
AB  - This report presents an exhaustive literature review on the toxicity of
      manufactured ZnO nanoparticles (NPs) to ecological receptors across different
      taxa: bacteria, algae and plants, aquatic and terrestrial invertebrates and
      vertebrates. Ecotoxicity studies on ZnO NPs are most abundant in bacteria, and
      are relatively lacking in other species. These studies suggest relative high
      acute toxicity of ZnO NPs (in the low mg/l levels) to environmental species,
      although this toxicity is highly dependent on test species, physico-chemical
      properties of the material, and test methods. Particle dissolution to ionic zinc
      and particle-induced generation of reactive oxygen species (ROS) represent the
      primary modes of action for ZnO NP toxicity across all species tested, and photo
      induced toxicity associated with its photocatalytic property may be another
      important mechanism of toxicity under environmentally relevant UV radiation.
      Finally, current knowledge gaps within this area are briefly discussed and
      recommendations for future research are made.

PMID- 22995931
TI  - The AL 333-160 fourth metatarsal from Hadar compared to that of humans, great
      apes, baboons and proboscis monkeys: non-conclusive evidence for pedal arches or
      obligate bipedality in Hadar hominins.
AB  - Based on comparisons to non-statistically representative samples of humans and
      two great ape species (i.e. common chimpanzees Pan troglodytes and lowland
      gorillas Gorilla gorilla), Ward et al. (2011) concluded that a complete hominin
      fourth metatarsal (4th MT) from Hadar, AL 333-160, belonged to a committed
      terrestrial biped with fixed transverse and longitudinal pedal arches, which was
      no longer under selection favoring substantial arboreal behaviors. According to
      Ward et al., the Hadar 4th MT had (1) a torsion value indicating a transverse
      arch, (2) sagittal plane angles between the diaphyseal long axis and the planes
      of the articular surfaces indicating a longitudinal arch, and (3) a narrow
      mediolateral to dorsoplantar base ratio, an ectocuneiform facet, and tarsal
      articular surface contours all indicating a rigid foot without an ape-like mid
      tarsal break. Comparisons of the Hadar 4th MT characters to those of
      statistically representative samples of humans, all five great ape species,
      baboons and proboscis monkeys show that none of the correlations Ward et al. make
      to localized foot function were supported by this analysis. The Hadar 4th MT
      characters are common to catarrhines that have a midtarsal break and lack fixed
      transverse or longitudinal arches. Further comparison of the AL 333-160 4th MT
      length, and base, midshaft and head circumferences to those of catarrhines with
      field collected body weights show that this bone is uniquely short with a large
      base. Its length suggests the AL 333-160 individual was a poor leaper with
      limited arboreal behaviors and lacked a longitudinal arch, i.e. its 4th MT long
      axis was usually held perpendicular to gravity. Its large base implies cuboid-4th
      MT joint mobility. A relatively short 4th MT head circumference indicates AL 333
      160 had small proximal phalanges with a restricted range of mobility. Overall, AL
      333-160 is most similar to the 4th MT of eastern gorillas, a slow moving
      quadruped that sacrifices arboreal behaviors for terrestrial ones. This study
      highlights evolutionary misconceptions underlying the practice of using localized
      anatomy and/or a single bony element to reconstruct overall locomotor behaviors
      and of summarizing great ape structure and behavior based on non-statistically
      representative samples of only a few living great ape species.

PMID- 22995933
TI  - Early symptom response to antipsychotic medication as a marker of subsequent
      symptom change: an eighteen-month follow-up study of recent episode
      schizophrenia.
AB  - BACKGROUND: Differences between early- and delayed-responders to antipsychotic
      medication as a marker of subsequent symptom change to 18months are unknown.
      AIMS: To examine the association between initial non-, early- and delayed
      response and subsequent symptom change up to 18months in the antipsychotic
      treatment of the symptoms of recent-episode schizophrenia. METHOD: Participants
      were from a double-blind randomized clinical trial of recent episode
      schizophrenia (n=263). Based on attainment of a 20% PANSS total change in the
      initial four weeks, the following groups were created and compared: "non-" (i.e.,
      no-response): "early-" (i.e. within 2weeks) and "delayed-" (i.e. 3-4weeks)
      responders. Mixed modeling was used to predict PANSS percent change with group,
      time and the time-group interaction. RESULTS: Analysis of the PANSS total percent
      change showed significant (p<.01) group, time, and time-group interaction
      effects. Compared to non-responders, early-responders maintained significantly
      greater total response from week 5 to 44, and delayed-responders from week 5 to
      20. After this time, non-responders and the other groups did not significantly
      differ on change. Generally, differences between the delayed- and early
      responders were not statistically significance. Results were similar on the PANSS
      positive, negative and general psychopathology symptom subscales. CONCLUSIONS:
      Early-response is marked by up to 39weeks of longer subsequent symptom response
      than non-response, and infrequently differs to delayed-response. This has
      implications for consideration of switching and clinical trial design.

PMID- 22995932
TI  - Determinants of incomplete penetrance and variable expressivity in heritable
      cardiac arrhythmia syndromes.
AB  - Mutations in genes encoding ion channel pore-forming alpha-subunits and accessory
      beta-subunits as well as intracellular calcium-handling proteins that
      collectively maintain the electromechanical function of the human heart serve as
      the underlying pathogenic substrate for a spectrum of sudden cardiac death (SCD)
      predisposing heritable cardiac arrhythmia syndromes, including long QT syndrome
      (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic
      polymorphic ventricular tachycardia (CPVT). Similar to many Mendelian disorders,
      the cardiac "channelopathies" exhibit incomplete penetrance, variable
      expressivity, and phenotypic overlap, whereby genotype-positive individuals
      within the same genetic lineage assume vastly different clinical courses as
      objectively assessed by phenotypic features such electrocardiographic
      abnormalities and number/type of cardiac events. In this Review, we summarize the
      current understanding of the global architecture of complex electrocardiographic
      traits such as the QT interval, focusing on the role of common genetic variants
      in the modulation of ECG parameters in health and the environmental and genetic
      determinants of incomplete penetrance and variable expressivity in the heritable
      cardiac arrhythmia syndromes most likely to be encountered in clinical practice.

PMID- 22995934
TI  - Anterior limb of the internal capsule in schizotypal personality disorder: fiber
      tract counting, volume, and anisotropy.
AB  - Mounting evidence suggests that white matter abnormalities and altered
      subcortical-cortical connectivity may be central to the pathology of
      schizophrenia (SZ). The anterior limb of the internal capsule (ALIC) is an
      important thalamo-frontal white-matter tract shown to have volume reductions in
      SZ and to a lesser degree in schizotypal personality disorder (SPD). While
      fractional anisotropy (FA) and connectivity abnormalities in the ALIC have been
      reported in SZ, they have not been examined in SPD. In the current study,
      magnetic resonance (MRI) and diffusion tensor imaging (DTI) were obtained in age-
      and sex-matched individuals with SPD (n=33) and healthy controls (HCs; n=38). The
      ALIC was traced bilaterally on five equally spaced dorsal-to-ventral axial slices
      from each participant's MRI scan and co-registered to DTI for the calculation of
      FA. Tractography was used to examine tracts between the ALIC and two key Brodmann
      areas (BAs; BA10, BA45) within the dorsolateral prefrontal cortex (DLPFC).
      Compared with HCs, the SPD participants exhibited (a) smaller relative volume at
      the mid-ventral ALIC slice level but not the other levels; (b) normal FA within
      the ALIC; (c) fewer relative number of tracts between the most-dorsal ALIC levels
      and BA10 but not BA45 and (d) fewer dorsal ALIC-DLPFC tracts were associated with
      greater symptom severity in SPD. In contrast to prior SZ studies that report
      lower FA, individuals with SPD show sparing. Our findings are consistent with a
      pattern of milder thalamo-frontal dysconnectivity in SPD than schizophrenia.

PMID- 22995935
TI  - Myeloid derived suppressor cells (MDSCs) can induce the generation of Th17
      response from naive CD4+ T cells.
AB  - IL-17 producing CD4(+) T cells (Th17) are identified as a subset of
      proinflammatory T cells present at the tumor site of various murine and human
      cancer cases and plays a crucial role in shaping the neoplastic process through
      fostering tumor angiogenesis and metastasis. However, the development of Th17
      response in the tumor microenvironment has not yet been fully elucidated. Herein,
      we make an attempt to disclose the involvement of tumor infiltrating antigen
      presenting cells (APCs), especially tumor associated macrophages (TAMs) and
      myeloid derived suppressor cells (MDSCs) to polarize naive CD4(+) T cells toward
      IL-17(+) T cells. We have found that MDSCs either isolated from the tumor site or
      generated in vitro are superior over TAMs to induce IL-17 production by naive
      CD4(+) T cells. Furthermore, we have shown that MDSCs mediated induction of IL
      17(+) T cell response is independent of MDSCs-T cell contact but crucially
      depends on the cytokines secreted by MDSCs. Our study will help to develop
      potential therapeutic strategies by harnessing the ability of MDSCs to induce IL
      17 production by CD4(+) T cells and thus restrict the generation of inflammatory
      Th17 population at the disease site.

PMID- 22995936
TI  - KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages.
AB  - IRF5 plays a key role in the induction of pro-inflammatory cytokines,
      contributing to the plasticity and polarisation of macrophages to an M1 phenotype
      and initiation of a potent T(H)1-T(H)17 response. To better understand the means
      of IRF5 transcriptional action, we conducted a screen for IRF5-interacting
      partners by affinity purification coupled to mass spectrometry and identified
      KAP1/TRIM28 as a novel protein-protein interaction partner of IRF5. KAP1 acts as
      a transcriptional co-repressor, chiefly via recruitment of complexes involved in
      chromatin silencing, such as histone deacetylases and methyltransferases. We
      mapped the N-terminus of IRF5, encompassing its DNA-binding domain together with
      a highly intrinsically disordered region, as crucial for the IRF5-KAP1
      interaction interface, and demonstrated that IRF5 can also form complexes with
      the methyltransferase SETDB1. Knockdown of KAP1 (TRIM28) gene expression in human
      M1 macrophages potentiated IRF5-mediated expression of TNF and other M1
      macrophage markers. This effect may be linked to methyltransferase activity of
      SETDB1, such as trimethylation of lysine 9 of histone 3 (H3K9me3), deposition of
      which was decreased at the human TNF locus upon KAP1 knockdown. Our study
      furthers an understanding of the complex molecular interactions between the TRIM
      and IRF protein families, and highlights a role of the inhibitory properties of
      KAP1 in association with IRF5-mediated gene expression.

PMID- 22995937
TI  - Transport of PEGylated liposomes from the splenic marginal zone to the follicle
      in the induction phase of the accelerated blood clearance phenomenon.
AB  - The accelerated blood clearance (ABC) phenomenon has been reported to enhance the
      clearance of PEGylated liposomes from the blood circulation when the liposomes
      are injected into the same animal repeatedly. We have shown that anti-PEG IgM
      production from splenic B cells is crucial in the ABC phenomenon. In this study,
      we describe the crucial role of marginal zone (MZ) B cells in the anti-PEG IgM
      production and recognition of PEGylated liposomes in the induction phase of ABC
      phenomenon. Suppression of the anti-PEG IgM production was correlated with the
      disappearance of IgM(high) cells in the MZ, particularly MZ-B cells, following
      cyclophosphamide (CPA)-treatment, confirming that splenic MZ-B cells are
      responsible for anti-PEG IgM production. The MZ-B cells stimulated by a first
      dose of PEGylated liposomes internalized the second dose of PEGylated liposomes
      in a PEG modification-dependent manner and transported the liposomes into the
      follicle (FO) region. To the best of our knowledge, this is the first report
      showing that PEGylated liposome is recognized by MZ-B cells and transported to
      the FO region like blood-borne antigens or immune complexes. It is likely that
      PEGylated liposomes are recognized as a TI-2 antigen by the first line of defense
      against life-threatening infections by blood-borne organisms. Our study may have
      implications for immunogenicity of synthesized polymer-grafted therapeutics
      including nanocarriers, nucleic acids and proteins.

PMID- 22995938
TI  - Virtual reality phacoemulsification training.

PMID- 22995939
TI  - Spectral-domain optical coherence tomography of Roth spots in multiple myeloma.

PMID- 22995940
TI  - Mechanisms compensating for visual field restriction in adolescents with damage
      to the retro-geniculate visual system.
AB  - BACKGROUND: To describe visual field (VF) outcome in three adolescents with
      damage to the optic radiation and to focus on mechanisms that may compensate the
      practical functional limitations of VF defects. DESIGN: Descriptive, prospective
      multi-case study in a hospital setting. PARTICIPANTS: Three teenagers with
      cerebral visual dysfunction because of damage to the retro-geniculate visual
      pathways. METHODS: Best-corrected visual acuity and eye alignment were assessed.
      Visual field function was tested with Goldmann perimetry, and with Rarebit,
      Humphrey Visual Field Analyzer and Esterman computerized techniques. Fixation was
      registered with video oculography during Rarebit examination. Magnetic resonance
      imaging of the brain illustrated brain damage and its relation to the posterior
      visual system. RESULTS: One of the three subjects had bilateral asymmetric white
      matter damage of immaturity, early-onset exotropia, and a relative homonymous VF
      defect, but normal binocular VF. The second subject also had bilateral asymmetric
      white matter damage of immaturity and showed an inferior right quadrantanopia,
      confirmed by the binocular field. Registration of fixation revealed automatic
      scanning during perimetry. The third subject had an almost total left homonymous
      hemianopia after resection of a brain tumour in the right temporal lobe. The
      hemianopia could be compensated for by fast voluntary scanning. CONCLUSION:
      Congenital and later-acquired homonymous VF defects may, at least in young
      subjects, be compensated for by scanning. Exotropia may compensate VF defects
      and, therefore, the VF should be tested before strabismus surgery.

PMID- 22995942
TI  - Verbal fluency in Parkinson's disease patients on/off dopamine medication.
AB  - INTRODUCTION: Parkinson's disease (PD) is associated with dopamine depletion in
      the fronto-striatal network which affects some language aspects such as verb
      processing. Some experiments have demonstrated that dopamine deficiency plays a
      role in the normal functioning of the lexico-semantic system. As a result, the
      verbal fluency task could be a useful tool to assess the function of the semantic
      system, by examining both the number of words generated and the frequency of use
      of those words. OBJECTIVE: The aim of this study was to find out how dopamine
      affects the performance of PD patients using a verbal fluency task, focussing on
      action-word fluency. METHOD: A group of 20 PD patients and 20 controls
      participated in the study. Participants were assessed with four different verbal
      fluency tasks: phonological, semantic (animal and supermarket words) and action
      fluency. PD patients were tested twice (on/off medication) and controls only
      once. RESULTS: For the number of words, there were significant differences
      between PD patients on and off medication in the phonological and action fluency
      tasks. Compared to controls, PD off medication produced significantly fewer words
      in phonological, and actions. Regarding frequency, differences were found between
      PD patients off medication and controls for the action-word category. DISCUSSION:
      Our data showed a specific deficit in PD patients off medication in categories
      mainly depending on frontal lobe function (phonological and actions) while these
      differences were restored with dopamine treatment. Moreover, PD patients off
      medication produced higher frequency verbs than controls, suggesting that
      dopamine affects the normal functioning within the lexico-semantic network of
      verbs.

PMID- 22995941
TI  - Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and
      intravitreal chemotherapy.
AB  - In this report, we explore retinoblastoma diagnostic accuracy and review
      chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial,
      periocular, and intravitreal routes. A review of 2775 patients referred for
      management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22%
      with simulating lesions, termed pseudoretinoblastomas. Children <=2 years old
      showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats
      disease, and vitreous haemorrhage, whereas those >5 years showed simulators of
      Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of
      retinoblastoma should be established before planning therapeutic strategy.
      Chemotherapy strategy depends on tumour laterality and stage of disease. If
      bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first
      line therapy for control of intraocular disease, prevention of metastasis, and
      reduction in prevalence of pinealoblastoma and long-term second malignant
      neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's
      carboplatin boost for improved local control. If unilateral disease is present,
      then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage
      therapy following chemoreduction failure. Unilateral retinoblastoma of groups D
      and E are managed with enucleation or globe-conserving IVC and/or IAC.
      Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds
      following other therapies. In conclusion, the strategy for retinoblastoma
      management with chemotherapy depends on tumour laterality and stage of disease.
      Bilateral retinoblastoma is most often managed with IVC and unilateral
      retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or
      enucleation.

PMID- 22995944
TI  - Psychometric properties of the Chinese versions of the Quick Inventory of
      Depressive Symptomatology - Clinician Rating (C-QIDS-C) and Self-Report (C-QIDS
      SR).
AB  - BACKGROUND: Developing accurate and time-efficient tools to measure depressive
      symptoms is important for research and clinical practice. This study aimed to
      test the psychometric properties of the Chinese version of the 16-item Quick
      Inventory of Depressive Symptomatology - Clinician Rating (C-QIDS-C) and Self
      Report (C-QIDS-SR). METHODS: This study included 998 patients with major
      depressive disorder (MDD) established using the Mini International
      Neuropsychiatric Interview (MINI). The severity of depressive symptoms was
      assessed using the Hamilton Rating Scale for Depression (HAMD), C-QIDS-C and C
      QIDS-SR at baseline and 6 weeks later. RESULTS: Internal consistency (Cronbach's
      alpha) ranged from 0.73 to 0.82 for C-QIDS-C and C-QIDS-SR at both the baseline
      and exit. The involvement and energy domains at baseline, and sad mood,
      concentration/decision making, self outlook, involvement and
      agitation/retardation domains at exit had the highest item-total correlations
      across the two C-QIDS scales. The C-QIDS-C and C-QIDS-SR total scores were highly
      correlated with the HAMD total score at both baseline (r=0.61, p<0.01 and r=0.54,
      p<0.01, respectively) and exit (r=0.75, p<0.01 and r=0.72, p<0.01, respectively).
      The C-QIDS-C, C-QIDS-SR and HAMD were equally sensitive to change of depressive
      symptoms, suggesting high concurrent validity. The C-QIDS-C and C-QIDS-SR showed
      uni-dimensional measurement properties in exploratory factor analyses at both
      baseline and exit. CONCLUSIONS: The C-QIDS-C and C-QIDS-SR have excellent
      psychometric properties and are sensitive measurement of symptom severity in MDD.

PMID- 22995946
TI  - Foreign body granulomatous reaction to silica, silicone, and hyaluronic acid in a
      patient with interferon-induced sarcoidosis.
AB  - We report the case of a patient who developed sarcoid granulomas 11 months after
      starting treatment with pegylated interferon alfa and ribavirin for chronic
      hepatitis C. The sites of the lesions were related to 3 different foreign bodies:
      silica in old scars on the skin, hyaluronic acid that had been injected into
      facial tissues, and silicone in an axillary lymph node draining the area of a
      breast implant. Systemic sarcoidosis was diagnosed on the basis of a history of
      dry cough and fever and blood tests that revealed elevated angiotensin converting
      enzyme and liver enzymes. Interruption of the antiviral therapy led to
      normalization of liver function tests and disappearance of the skin lesions and
      lymphadenopathies. Dermatologists and cosmetic surgeons should be aware of the
      risk of sarcoid lesions related to cosmetic implants in patients who may require
      treatment with interferon in the future. 

PMID- 22995947
TI  - Papular acantholytic dermatosis in the genito-crural region: a localized form of
      Darier disease or Hailey-Hailey disease?

PMID- 22995943
TI  - Neural responses to incongruency in a blocked-trial Stroop fMRI task in major
      depressive disorder.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) perform poorly on the
      Stroop task, which is a measure of the executive control of attention, with
      impaired interference resolution. The neural correlates of this deficit are not
      well described. To examine how this deficit relates to pathophysiological
      abnormalities in MDD, we conducted an fMRI Stroop study comparing MDD subjects to
      controls. METHODS: Forty-two unmedicated patients with current MDD and 17 control
      subjects underwent fMRI scanning with a color-word Stroop task. Subjects assessed
      font color during alternating color identification (e.g., 'XXXX' in blue) and
      incongruent color/word blocks (e.g., the word 'red' in blue). We examined neural
      activation that was greater in incongruent than color identification blocks
      (Z>2.3 and corrected p<0.05), controlling for trial-by-trial reaction time.
      RESULTS: Compared to controls, MDD subjects exhibited lower activation during
      incongruent blocks across multiple brain regions, including middle frontal gyrus,
      paracingulate and posterior cingulate, precuneus, occipital regions, and brain
      stem. No brain regions were identified in which MDD subjects were more active
      than controls during incongruent blocks. LIMITATIONS: Not all MDD subjects were
      antidepressant-naive. CONCLUSIONS: Brain regions related to executive function,
      visual processing, and semantic processing are less active during processing of
      incongruent stimuli in MDD subjects as compared to controls. Deficits of
      attention in MDD may be the product of a failure to maintain activity across a
      distributed network in a sustained manner, as is required over the sequential
      trials in this block design. Further studies may clarify whether the
      abnormalities represent a trait or state deficit.

PMID- 22995948
TI  - Macular arteritis: a pole of the spectrum of cutaneous polyarteritis nodosa?

PMID- 22995949
TI  - Immunohistochemistry in dermatopathology: a review of the most commonly used
      antibodies (part II).
AB  - Dermatopathology includes a long list of disorders, some of which have very
      similar histopathology. Immunohistochemistry is an important auxiliary tool for
      diagnosis and differential diagnosis, and for predicting the outcome of many skin
      tumors. It is also the main technique for determining the origin of a tissue or
      the differentiation of neoplastic cells. In many cases, immunohistochemistry
      provides a more accurate diagnosis of the different processes that infiltrate the
      skin. This review examines the role of immunohistochemistry in studying the
      differentiation and biological behavior of the majority of tumors that can
      involve the skin. We review immunoperoxidase techniques, discuss the utility of
      the most commonly used antibodies, and highlight a number of diagnostic problems
      in which immunohistochemistry may be very useful. In each case, the goal is to
      reach a specific and definitive diagnosis. In the second part of our review, we
      examine the most useful and specific antibodies in the study of skin infections
      and of epithelial, muscular, lymphatic and hematologic, neural, neuroendocrine,
      and melanocytic neoplasms that affect the skin. Finally, we include a brief
      review of the immunohistochemical profile of skin metastases of malignant
      visceral tumors.

PMID- 22995950
TI  - Scientific yellow journalism.

PMID- 22995951
TI  - Rapid neurologic decline in a patient with peripheral T-cell lymphoma: a case of
      leptomeningeal lymphomatosis.

PMID- 22995952
TI  - Vitreoretinal lymphoma: changing trends in diagnosis and local treatment
      modalities at a single institution.
AB  - In this retrospective study on vitreoretinal lymphoma, there was significant
      change in diagnosis and treatment trends over 17 years at a single institution.
      Fine needle aspiration biopsy had replaced vitrectomy to collect vitreous sample
      and external beam radiotherapy in combination with systemic chemotherapy was
      replaced by intravitreal methotrexate and rituximab, which regressed
      vitreoretinal lymphoma (VRL) with no relapses or major ocular complications.
      INTRODUCTION: The purpose of this study was to report the changing trends in
      treatment (external beam radiotherapy [EBRT] and intravitreal chemotherapy) of
      VRL and treatment outcomes at a single institution. MATERIALS AND METHODS: A
      retrospective chart review of vitreous biopsy proven patients was performed. The
      data analysis included demographics, systemic lymphoma status, ocular symptoms,
      clinical and immunocytological findings, treatment methods, and response
      (intravitreal methotrexate 300 MUg/0.05 mL, 1000 MUg/0.1 mL of rituximab and EBRT
      36-45 Gy) and ocular and systemic lymphoma outcomes at last follow-up. RESULTS:
      Twelve eyes of 8 patients had intraocular B-cell lymphoma (median age, 61 years;
      range, 50-83). Central nervous system non-Hodgkin's lymphoma (CNS-NHL) was
      present in 7 of 8 patients. Most common ocular symptoms were diminution of vision
      in 4 and floaters in 3 patients. Iritis and uveitis were found in 6 eyes and
      vitritis in 11 eyes. Retinal infiltrates were present in 8 eyes. Immunocytology
      revealed elevated levels of interleukin (IL)-10 (12,783.5 pg/mL), IL-6 (26.7
      pg/mL), and IgH gene rearrangement. Three patients were treated with EBRT, 6 eyes
      with intravitreal methotrexate (median, 9.5; range, 2-15), and 2 eyes with
      intravitreal rituximab injections (median, 4; range, 2-6). Two patients developed
      marked keratitis because of methotrexate toxicity. At median follow-up of 33.5
      months (range, 4-96), VRL had resolved in 7 eyes and persistent in 5 eyes. One
      patient died because of advanced CNS-NHL. CONCLUSION: Intravitreal chemotherapy
      provided good control rates for VRL patients in our limited series. Patients with
      associated CNS-NHL had poorer outcomes.

PMID- 22995955
TI  - Meaning.

PMID- 22995953
TI  - Glaucomatous damage of the macula.
AB  - There is a growing body of evidence that early glaucomatous damage involves the
      macula. The anatomical basis of this damage can be studied using frequency domain
      optical coherence tomography (fdOCT), by which the local thickness of the retinal
      nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform
      (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy
      controls and patients, we show that: 1. For healthy controls, the average RGC+
      layer thickness closely matches human histological data; 2. For glaucoma patients
      and suspects, the average RGC+ layer shows greater glaucomatous thinning in the
      inferior retina (superior visual field (VF)); and 3. The central test points of
      the 6 degrees  VF grid (24-2 test pattern) miss the region of greatest RGC+
      thinning. Based upon fdOCT results from individual patients, we have learned
      that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as
      the displacement of RGCs from the foveal center is taken into consideration; and
      2. Macular damage is typically arcuate in nature and often associated with local
      RNFL thinning in a narrow region of the disc, which we call the macular
      vulnerability zone (MVZ). According to our schematic model of macular damage,
      most of the inferior region of the macula projects to the MVZ, which is located
      largely in the inferior quadrant of the disc, a region that is particularly
      susceptible to glaucomatous damage. A small (cecocentral) region of the inferior
      macula, and all of the superior macula (inferior VF), project to the temporal
      quadrant, a region that is less susceptible to damage. The overall message is
      clear; clinicians need to be aware that glaucomatous damage to the macula is
      common, can occur early in the disease, and can be missed and/or underestimated
      with standard VF tests that use a 6 degrees  grid, such as the 24-2 VF test.

PMID- 22995954
TI  - Clinical applications of retinal gene therapy.
AB  - Many currently incurable forms of blindness affecting the retina have a genetic
      etiology and several others, such as those resulting from retinal vascular
      disturbances, respond to repeated, potentially indefinite administration of
      molecular based treatments. The recent clinical advances in retinal gene therapy
      have shown that viral vectors can deliver genes safely to the retina and the
      promising initial results from a number of clinical trials suggest that certain
      diseases may potentially be treatable. Gene therapy provides a means of
      expressing proteins within directly transduced cells with far greater efficacy
      than might be achieved by traditional systemic pharmacological approaches. Recent
      developments have demonstrated how vector gene expression may be regulated and
      further improvements to vector design have limited side effects and improved
      safety profiles. These recent steps have been most significant in bringing gene
      therapy into the mainstream of ophthalmology. Nevertheless translating retinal
      gene therapy from animal research into clinical trials is still a lengthy
      process, including complexities in human retinal diseases that have been
      difficult to model in the laboratory. The focus of this review is to summarize
      the genetic background of the most common retinal diseases, highlight current
      concepts of gene delivery technology, and relate those technologies to pre
      clinical and clinical gene therapy studies.

PMID- 22995956
TI  - Comment on "inevitable suicide".

PMID- 22995957
TI  - Consequences of "inevitable suicide".

PMID- 22995959
TI  - Valuation and attainment of treatment goals in schizophrenia:  perspectives of
      patients, relatives, physicians, and payers.
AB  - OBJECTIVE: This study investigated and compared the valuation and perceived
      attainment of multiple treatment goals in schizophrenia from the perspectives of
      four different groups of stakeholders. METHOD: Twenty treatment goals (identified
      in a qualitative patient-based pre-study) were ranked and rated according to
      their relevance in standardized interviews. Goal attainment was also rated. A
      rank correlation was computed to identify congruencies among the stakeholder
      groups. A hierarchical cluster analysis of the data from the stakeholders groups
      was also conducted. RESULTS: In this study, 105 outpatients, 160 physicians, 50
      relatives, and 30 payers were interviewed. All goals were considered very
      relevant by all stakeholder groups. "Improved cognitive abilities" was ranked
      among the top three goals by patients, physicians, and relatives, while "reduced
      disease-related symptoms" was ranked first by relatives and second by physicians.
      Payers gave the highest priority to goals that were more likely to affect costs
      (i.e., ability to resume work, reduced disease-related symptoms, less
      hospitalization/ need for outpatient visits). Pairwise agreement rates ranged
      from 38.9% to 63.3%. Rank correlations were found between relatives and patients
      (r=0.51; P=0.002), relatives and physicians (r=0.43; P=0.008), and payers and
      patients (r=0.43; P=0.008). The cluster analysis revealed a relevant congruency
      among patients, relatives, and physicians. Goal attainment was rated lower than
      goal relevance by all groups, with patients judging attainment the best on
      average, followed by relatives, physicians, and payers. Reduction in disease
      related symptoms was rated as the goal that was best achieved. CONCLUSION:
      Discordances among the groups with respect to their valuation of treatment goals
      should encourage stakeholders to better understand others' preferences as a
      prerequisite for improved shared decision making and potentially improved
      treatment outcomes.

PMID- 22995960
TI  - Race- and gender-related differences in clinical characteristics and quality of
      life among outpatients with psychotic disorders.
AB  - BACKGROUND: Historically, the literature suggests that African Americans with
      mental illness are diagnosed with psychotic disorders at a higher rate and
      receive higher doses of antipsychotic medications than other racial groups.
      However, few studies have compared clinical characteristics and quality of life
      among African-American (AA) and white men and women. Thus, research is needed to
      examine potential race and gender differences in clinical characteristics,
      prescribing practices, and quality of life. METHODS: This exploratory, hypothesis
      generating study examined current and past diagnoses, current pharmacotherapy,
      failed psychotropic medications, and quality of life among 23 AA and 31 white men
      and women receiving outpatient treatment for psychosis. RESULTS: Depression and
      psychotic depression were common complaints in the sample, yet only a third of
      the patients received antidepressants. We found that AA men received an
      antidepressant for depression symptoms less often, received higher antipsychotic
      doses, and rated their overall quality of life as poorer than any other group.
      White men and AA women had a history of more years of mental illness and had
      experienced 57% and 69% more psychotropic medication failures, respectively, than
      AA men or white women. Quality of life scores were significantly related to years
      of mental illness, number of past diagnoses, and number of failed medications.
      CONCLUSIONS: Our data suggest that clinicians could significantly enhance
      prognostic outcomes in outpatients with psychotic disorders by routinely re
      evaluating depressive symptomatology and prescribing practices and considering
      adding psychosocial interventions to avert deterioration in quality of life.
      Further investigation of race and gender differences in quality of life and
      satisfaction as a function of diagnoses and treatment is warranted.

PMID- 22995961
TI  - The meaning of antipsychotic medication to patients with schizophrenia.
AB  - OBJECTIVE: To explore the meaning of taking antipsychotic medication in a
      population with schizophrenia. METHOD: A literature review of publications on the
      meaning of medication was conducted using PsycINFO, Medline, and SOCINDEX
      databases (2001-2012) and search terms attitude or meaning plus antipsychotics or
      neuroleptics. Based on this search, 110 articles were found, 60 of which were
      judged relevant to the goal of this article. A recently published expert
      consensus guideline was also used to better understand current thinking about
      medication adherence issues in patients with severe mental illness. Quotations
      from patients attending a women's clinic for psychosis were used to expand on
      themes found in the literature. RESULTS: Themes extracted from the reviewed
      literature fell into three main categories: a) control by and of medication, b)
      dependence on medication and on the prescriber, and c) stigma resulting from
      medication use. These themes contrast with the usual medical associations with
      medication (e.g., symptom relief or side effects). CONCLUSION: Shared discussion
      of beliefs about medication between patient and care provider allows wider
      exploration of personal meanings that can help establish therapeutic
      relationships and integrate psychological therapy with psychopharmacology.

PMID- 22995962
TI  - Mental health, concurrent disorders, and health care utilization in homeless
      women.
AB  - PURPOSE: This study assessed lifetime and current prevalence rates of mental
      disorders and concurrent mental and substance use disorders in a sample of
      homeless women. Current suicide risk and recent health service utilization were
      also examined in order to understand the complex mental health issues of this
      population and to inform the development of new treatment strategies that better
      meet their specific needs. METHODS: A cross-sectional survey of 196 adult
      homeless women in three different Canadian cities was done. Participants were
      assessed using DSM-IV-based structured clinical interviews. Current diagnoses
      were compared to available mental health prevalence rates in the Canadian female
      general population. RESULTS: Current prevalence rates were 63% for any mental
      disorder, excluding substance use disorders; 17% for depressive episode; 10% for
      manic episode; 7% for psychotic disorder; 39% for anxiety disorders, 28% for
      posttraumatic stress disorder; and 19% for obsessive-compulsive disorder; 58% had
      concurrent substance dependence and mental disorders. Lifetime prevalence rates
      were notably higher. Current moderate or high suicide risk was found in 22% of
      the women. Participants used a variety of health services, especially emergency
      rooms, general practitioners, and walk-in clinics. CONCLUSION: Prevalence rates
      of mental disorders among homeless participants were substantially higher than
      among women from the general Canadian population. The percentage of participants
      with moderate or high suicide risk and concurrent disorders indicates a high
      severity of mental health symptomatology. Treatment and housing programs need to
      be accompanied by multidisciplinary, specialized interventions that account for
      high rates of complex mental health conditions.

PMID- 22995963
TI  - Clinically important differences in the pharmacokinetics of the ten newer
      "atypical" antipsychotics: Part 2. Metabolism and elimination.
AB  - The "atypical" antipsychotics are grouped together based on what they are not
      (i.e., not dopamine-2 selective antagonists like haloperidol). While sharing this
      characteristic, these agents differ substantially in pharmacokinetics and
      pharmacodynamics. The first column in this series reviewed the bioavailability
      and half-life of the 10 newer "atypical" antipsychotics, including the most
      recently market- ed members of this class (asenapine, iloperidone, and
      lurasidone). This second column in the series discusses the metabolism of these
      agents, including principal enzyme(s) mediating each drug's clearance and effects
      of co-administering substantial CYP enzyme inhibitors. 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. For deeper
      understanding of the principles behind the specifics discussed here, the concepts
      of "special populations" and phase I versus phase II metabolism are discussed in
      the introduction. An understanding of these principals and the specific
      pharmacokinetic differences among the "atypical" antipsychotics can help
      clinicians optimize drug selection and dose for specific patients under specific
      treatment conditions. The third column in this series will discuss the effects of
      hepatic and renal impairment on dosing recommendations, and a subsequent column
      in the series will review the substantial and clinically important
      pharmacodynamic differences among these agents.

PMID- 22995964
TI  - The dilemma of the rural psychiatrist.
AB  - Rural areas provide unique opportunities and challenges for delivery of
      psychiatric care. This is especially true for the psychiatrist trained in
      psychotherapy. As patients become more aware of the risk/benefit profiles of
      medications, there is a growing demand for psychotherapy services in all parts of
      this country. This creates particular challenges for rural areas, which also face
      unique difficulties in recruitment. The author discusses her personal experience
      as a psychiatrist and psycho- analyst in private practice in an underserved area.
      Misconceptions and misinformation about practice in rural areas are explored.

PMID- 22995965
TI  - Outpatient triple chronotherapy for bipolar depression:  case report.
AB  - There is an urgent need for rapid, effective, and safe treatments for bipolar
      depression. Triple chronotherapy is a combination of sleep deprivation, sleep
      phase advance, and bright light therapy that has been shown to induce accelerated
      and sustained remissions in bipolar depression. This case report describes the
      first outpatient program designed to administer triple chronotherapy and reviews
      the organizational and clinical requirements for providing such care.

PMID- 22995966
TI  - Using structured clinical feedback to encourage alternatives to use of "P.R.N."
      medication in a state psychiatric hospital.
AB  - OBJECTIVE: The study examined whether reductions in the use of pro re nata
      (p.r.n.) psychotropic medications could be achieved in a large public-sector
      psychiatric hospital, without adverse behavioral consequences, by disseminating a
      database that tracks p.r.n. use to clinical teams. METHODS: A performance
      improvement project was implemented over 28 months, involving all 166 patients in
      one section of a state psychiatric hospital. A spread- sheet tracking p.r.n.
      administration for each patient was provided weekly to unit treatment teams.
      Clinical outcome monitoring focused on the number of p.r.n. administrations and
      on p.r.n. "events," defined as >= 3 multiple administrations per week and >= 10
      per month. Episodes of patient seclusion, restraint, and violent incidents were
      also monitored. RESULTS: From September 2008 to December 2010, with a stable
      patient population census, total monthly administrations of psychotropic p.r.n.
      medications decreased from 642 to 240; administrations of non-psychotropic
      "medical" p.r.n. agents also decreased, from 279 to 72. In year-by-year
      comparisons, significant decreases (P < 0.05) were observed in the total number
      of psychotropic and medical p.r.n. administrations, in weekly as well as monthly
      p.r.n. events, and in the number of patients receiving any p.r.n.
      administrations. There was no change from 2008 to 2010 in the number of violent
      incidents; the use of both seclusion and restraint decreased (P < 0.05).
      CONCLUSION: The findings suggest that p.r.n. use can be reduced safely through
      timely feedback of relevant clinical data.

PMID- 22995967
TI  - Same-day cataract surgery should be the standard of care for patients with
      bilateral visually significant cataract.
AB  - Same-day, or immediately sequential, bilateral cataract surgery (ISBCS) is being
      practiced with increasing frequency worldwide. It provides many advantages
      including convenience for the patient and the patient's family. ISBCS repairs the
      visual system, not merely one eye, restoring normal binocularity as well as
      unilateral clarity, creates a much more relaxed surgical atmosphere in harried
      operating rooms, and saves money for society. It is often preferred by busy
      professionals. The purported risks of ISBCS have been unsupported by the
      literature, including bilateral retinal detachment, bilateral corneal
      decompensation, bilateral diabetic macular edema, bilateral severe cystoid
      macular edema, significant IOL power errors in the first eye that could be
      refined and thereby prevented in the second eye, and toxic anterior segment
      syndrome. The greatest fear of ISBCS has been possible simultaneous bilateral
      endophthalmitis, which did not occur in a series of nearly 100,000 ISBCS cases
      and has only occurred elsewhere when complete separation of the two eyes and
      strict sterile protocol were not followed. The International Society of Bilateral
      Cataract Surgeons (www.isbcs.org) has prepared the "iSBCS General Principles for
      Excellence in ISBCS," which should be followed for safe ISBCS.

PMID- 22995968
TI  - Same-day cataract surgery should not be the standard of care for patients with
      bilateral visually significant cataract.
AB  - Benefits of sequential surgery include assessment of the outcome of the first
      surgery to tailor the surgical technique, intraocular lens (IOL) power, and
      choice of IOL for the second surgery. Additionally, recovery may be prolonged
      from corneal edema, anterior chamber inflammation, or cystoid macular edema.
      Allowing the patient to maintain visual function in one eye during the recovery
      of the other eye can be important. Therefore, the few benefits of simultaneous
      surgery are greatly outweighed by risks of bilateral complications, inability to
      foresee refractive outcome, inability to alter IOL choice, potential loss of
      physician reimbursement, and possible increased legal ramifications.

PMID- 22995969
TI  - Evaluation of Seebeck coefficients in n- and p-type silicon nanowires fabricated
      by complementary metal-oxide-semiconductor technology.
AB  - Silicon-based thermoelectric nanowires were fabricated by using complementary
      metal-oxide-semiconductor (CMOS) technology. 50 nm width n- and p-type silicon
      nanowires (SiNWs) were manufactured using a conventional photolithography method
      on 8 inch silicon wafer. For the evaluation of the Seebeck coefficients of the
      silicon nanowires, heater and temperature sensor embedded test patterns were
      fabricated. Moreover, for the elimination of electrical and thermal contact
      resistance issues, the SiNWs, heater and temperature sensors were fabricated
      monolithically using a CMOS process. For validation of the temperature
      measurement by an electrical method, scanning thermal microscopy analysis was
      carried out. The highest Seebeck coefficients were - 169.97 MUV K(-1) and 152.82
      MUV K(-1) and the highest power factors were 2.77 mW m(-1) K(-2) and 0.65 mW m(
      1) K(-2) for n- and p-type SiNWs, respectively, in the temperature range from 200
      to 300 K. The larger power factor value for n-type SiNW was due to the higher
      electrical conductivity. The total Seebeck coefficient and total power factor for
      the n- and p-leg unit device were 157.66 MUV K(-1) and 9.30 mW m(-1) K(-2) at 300
      K, respectively.

PMID- 22995971
TI  - Relation of gender-specific risk of ischemic stroke in patients with atrial
      fibrillation to differences in warfarin anticoagulation control (from AFFIRM).
AB  - Warfarin decreases risk of stroke for patients with atrial fibrillation (AF)
      dependent on percent time in the therapeutic range (TTR) with an international
      normalized ratio (INR) of 2 to 3. We hypothesized that gender differences in
      ischemic stroke risk are related to TTR. From the AFFIRM database of 4,060
      patients with AF, we determined the incidence of ischemic stroke by gender. We
      evaluated the INR at time of ischemic stroke and calculated TTR. We determined
      the relation between gender and ischemic stroke by TTR. Women had CHADS(2) Scores
      (3.7 +/- 1.3 vs 2.5 +/- 1.3, p <0.0001) and more ischemic strokes than men (5% vs
      3%, odds ratio 1.6, 95% confidence interval 1.19 to 2.26, p = 0.002). Mean INR
      near time of ischemic stroke was 2 for women and men; median values were
      subtherapeutic (1.7 and 1.8, respectively). Women spent more time outside the
      therapeutic range (40 +/- 0.7% vs 37 +/- 0.5%, p = 0.0001), with more time below
      the therapeutic range (29 +/- 0.7% vs 26 +/- 0.5%, p = 0.0002). A higher TTR
      protected against ischemic stroke for women but not for men. Women who had a
      comparably high TTR (>=66%) still had more ischemic strokes (p = 0.009). A fitted
      Cox proportional hazard regression model showed that gender, TTR <46% versus
      >80%, age, and previous stroke were significantly related to stroke incidence. In
      conclusion, women in AFFIRM were at greater risk of ischemic stroke than men, in
      part related to differences in TTR. Women with AF may benefit from more
      aggressive or novel anticoagulation to decrease their risk of stroke.

PMID- 22995970
TI  - Von Willebrand factor and the right ventricle (the MESA-Right Ventricle Study).
AB  - Elevation in plasma activity of von Willebrand factor (vWF) reflects endothelial
      dysfunction and predicts death in pulmonary arterial hypertension. Higher vWF
      activity is also associated with a lower right ventricular (RV) ejection fraction
      in pulmonary arterial hypertension. Little is known about the relation between
      vWF and RV structure and function in adults without cardiovascular disease. The
      present investigation included 1,976 participants with magnetic resonance imaging
      assessment of RV structure and function and measurement of vWF activity from the
      Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used
      to estimate the associations between vWF activity and measures of RV structure
      and function after adjusting for demographics, anthropometrics, smoking, diabetes
      mellitus, hypertension, and the corresponding left ventricular parameter. The
      average vWF activity was 140.7 +/- 57.2%. Elevated vWF activity was independently
      associated with lower RV mass, RV end-diastolic volume, and RV stroke volume in
      models with and without adjustment for the corresponding left ventricular
      parameter (all p values <0.05). There was no association observed between vWF
      activity and the RV ejection fraction. In conclusion, higher vWF activity is
      associated with lower RV mass, RV end-diastolic volume, and RV stroke volume.
      These associations are independent of common cardiovascular risk factors and left
      ventricular morphologic changes.

PMID- 22995972
TI  - Does early improvement predict response to the fast-dissociating D2 receptor
      antagonist JNJ-37822681 in patients with acute schizophrenia?
AB  - Early predictability of sustained response to atypical antipsychotics in patients
      with schizophrenia has important implications for clinical decision making. In
      order to investigate whether early onset of efficacy correlates with week-6
      response for the selective fast-dissociating D2 receptor antagonist JNJ-37822681,
      we analysed data from a 12-week placebo- and active-controlled (olanzapine) study
      designed to evaluate efficacy and safety of JNJ-37822681. Factors, including
      baseline Positive and Negative Syndrome Scale (PANSS) total score, waist
      circumference, weight, body mass index group, number of previous
      hospitalisations, age at diagnosis, race, sex and age at study entry, and
      relative (%) change from baseline on day 3 (early improvement) in PANSS total
      score, were analysed using logistic regression models and receiver operator
      characteristic (ROC) curve analysis, to predict the week-6 efficacy response (>=
      30% improvement in PANSS total score). Results showed that week-6 response with
      JNJ-37822681 30 mg bid treatment could be reliably predicted by improvement in
      PANSS total score on day 3, the number of previous hospitalisations, and race
      (80% accuracy [ROC area under curve]). Early improvement (day 3) in PANSS score
      had the highest predictive value as a single factor across all JNJ-37822681
      doses. At a specificity of 70%, sensitivity for predicting week-6 response was:
      0.60, 0.64, and 0.74 in the 10-, 20-, and 30 mg bid JNJ-37822681 groups,
      respectively; 0.40 in olanzapine group. Early improvement in PANSS may be a
      simple and reliable way to predict sustained response with JNJ-37822681 in
      patients with acute schizophrenia.

PMID- 22995973
TI  - The promise of choline-PET/CT in the detection of recurrent prostate cancer: what
      are the limits of our investigation?

PMID- 22995974
TI  - ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion.
AB  - CONTEXT: A summary of the 2nd International Consultation on Bladder Cancer
      recommendations on the reconstructive options after radical cystectomy (RC),
      their outcomes, and their complications. OBJECTIVE: To review the literature
      regarding indications, surgical details, postoperative care, complications,
      functional outcomes, as well as quality-of-life measures of patients with
      different forms of urinary diversion (UD). EVIDENCE ACQUISITION: An English
      language literature review of data published between 1970 and 2012 on patients
      with UD following RC for bladder cancer was undertaken. No randomized controlled
      studies comparing conduit diversion with neobladder or continent cutaneous
      diversion have been performed. Consequently, almost all studies used in this
      report are of level 3 evidence. Therefore, the recommendations given here are
      grade C only, meaning expert opinion delivered without a formal analysis.
      EVIDENCE SYNTHESIS: Indications and patient selection criteria have significantly
      changed over the past 2 decades. Renal function impairment is primarily caused by
      obstruction. Complications such as stone formation, urine outflow, and
      obstruction at any level must be recognized early and treated. In patients with
      orthotopic bladder substitution, daytime and nocturnal continence is achieved in
      85-90% and 60-80%, respectively. Continence is inferior in elderly patients with
      orthotopic reconstruction. Urinary retention remains significant in female
      patients, ranging from 7% to 50%. CONCLUSIONS: RC and subsequent UD have been
      assessed as the most difficult surgical procedure in urology. Significant
      disparity on how the surgical complications were reported makes it impossible to
      compare postoperative morbidity results. Complications rates overall following RC
      and UD are significant, and when strict reporting criteria are incorporated, they
      are much higher than previously published. Fortunately, most complications are
      minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery,
      emphasizing the need for lifelong monitoring. Evidence suggests an association
      between surgical volume and outcome in RC; the challenge of optimum care for
      elderly patients with comorbidities is best mastered at high-volume hospitals by
      high-volume surgeons. Preoperative patient information, patient selection,
      surgical techniques, and careful postoperative follow-up are the cornerstones to
      achieve good long-term results.

PMID- 22995975
TI  - Acute deep vein thrombosis and endovascular techniques: It is time for a new
      aggiornamento!
AB  - The stated aims of treating acute deep vein thrombosis (DVT) are to prevent a
      pulmonary embolism, stop the clot from spreading, reduce the risk of a
      recurrence; they are less concerned with the late morbidity associated with post
      thrombotic syndrome (PTS). In accordance with the French (Afssaps, 2009) and
      North American (ACCP, 2008) recommendations, anticoagulants (LMWH, heparin, AVK)
      form the cornerstone for treating DVT. These treatments appear to be far less
      effective in preventing post-thrombotic syndrome (PTS), associated with venous
      hypertension, residual occlusion, and with reflux caused by valve incompetence.
      Given that, the new aim is to optimise the prevention of PTS, the ACCP
      guidelines, unlike those of Afssaps, "suggest" for selected patients suffering
      from acute iliofemoral DVT, the use of both classic anticoagulants, and in situ
      percutaneous administration of thrombolytic drugs (recommendation grade 2B) and
      simultaneous correction of any underlying anatomical anomalies using angioplasty
      and stenting (recommendation 2C). Contemporary endovascular methods, referred to
      collectively as "facilitated" thrombolysis, combine low doses of rtPa or
      Urokinase administered locally, and the removal of the clot using various
      mechanical, rotating, rheolytic systems, or using ultrasound. The results of non
      randomised, heterogeneous studies objectivised a lysis rate of 80%, a 50% lower
      risk of haemorrhage complications compared with systemic thrombolysis (<4%), and
      a clear reduction in treatment time (one-shot methods possible for procedures
      lasting less than 2 hours). This data ties in with the modern "open vein" concept
      which underpins the hope of an improvement in the late prognosis of acute DVT,
      through the removal of a clot, thereby improving permeability and valve
      integrity; this hypothesis is supported by the results at 24 months of a
      randomised CaVent objectifying absolute risk reduction of 15% in the thrombolysis
      in situ. The current randomised study (ATTRACT trial) comparing the combination
      of "facilitated thrombolysis" in addition to the usual treatment with the
      traditional treatment alone for acute iliofemoral DVT, the statistical power of
      which has been established (600 patients) to authenticate a reduction by a third
      in the number of PTS (CaVent trial, showing a 15% reduction rate of 24 months PTS
      in the thrombolysed group results expected in 2016), might, if the results are
      positive, lead to a profound change in the paradigms for the treatment of acute
      iliofemoral DVT.

PMID- 22995976
TI  - Metabolic consequences of chronic sleep restriction in rats: changes in body
      weight regulation and energy expenditure.
AB  - Epidemiological studies have shown an association between short or disrupted
      sleep and an increased risk to develop obesity. In animal studies, however, sleep
      restriction leads to an attenuation of weight gain that cannot be explained by
      changes in energy intake. In the present study, we assessed whether the
      attenuated weight gain under conditions of restricted sleep is a consequence of
      an overall increase in energy expenditure. Adult male rats were subjected to a
      schedule of chronic sleep restriction (SR) for 8 days with a 4h window of
      unrestricted rest per day. Electroencephalogram and electromyogram recordings
      were performed to quantify the effect of the sleep restriction schedule on sleep
      wake patterns. In a separate experiment, we measured sleep restriction-induced
      changes in body weight, food intake, and regulatory hormones such as glucose,
      insulin, leptin and corticosterone. To investigate whether a change in energy
      expenditure underlies the attenuation of weight gain, energy expenditure was
      measured by the doubly labeled water method from day 5 until day 8 of the SR
      protocol. Results show a clear attenuation of weight gain during sleep
      restriction but no change in food intake. Baseline plasma glucose, insulin and
      leptin levels are decreased after sleep restriction which presumably reflects the
      nutritional status of the rats. The daily energy expenditure during SR was
      significantly increased compared to control rats. Together, we conclude that the
      attenuation of body weight gain in sleep restricted rats is explained by an
      overall increase in energy expenditure together with an unaltered energy intake.

PMID- 22995977
TI  - Sweet taste and chorda tympani transection alter capsaicin-induced lingual pain
      perception in adult human subjects.
AB  - Sweetness signals the nutritional value of food and may moreover be accompanied
      by a sensory suppression that leads to higher pain tolerance. This effect is well
      documented in infant rats and humans. However, it is still debated whether
      sensory suppression is also present in adult humans. Thus, we investigated the
      effects of sweet taste on the perception of the painful trigeminal stimulus
      capsaicin in two groups of healthy adult human subjects. A solution of 100 MUM
      capsaicin was applied to the tip of the subject's tongues in order to stimulate
      trigeminal Adelta- and C-fiber nociceptors. When swallowed, 1M sucrose reduced
      the capsaicin-induced burning sensation by 29% (p <= 0.05) whereas a solution of
      similar taste intensity containing 1 MUM quinine did not. Similarly, sucrose
      application to the frontal hemitongue suppressed the perception of the burning
      sensation induced by contralaterally applied capsaicin by 25% (p <= 0.01). We
      furthermore investigated the effects of documented unilateral transection of the
      chorda tympani nerve on capsaicin perception. In accordance with the ipsi-to
      contralateral effect of sucrose on capsaicin perception in healthy subjects,
      hemiageusic subjects were more sensitive for capsaicin on the tongue
      contralateral to the taste nerve lesion (+38%; p <= 0.01). Taken together, these
      results argue I) for the existence of food intake-induced sensory suppression, if
      not analgesia, in adult humans and II) a centrally mediated suppression of
      trigeminal sensation by taste inputs that III) becomes disinhibited upon
      peripheral taste nerve lesion.

PMID- 22995979
TI  - Facilitation of intracranial self-stimulation behavior in rats by environmental
      stimuli associated with nicotine.
AB  - Environmental stimuli associated with nicotine act as a trigger for nicotine
      seeking behavior and make it difficult to quit smoking. The trigger action might
      be related to the activity of the mesolimbic dopamine "reward" system. Thus, in
      the present study, we investigated the effects of nicotine-associated stimuli on
      reward seeking, assessed by current intensity thresholds of intracranial self
      stimulation (ICSS) in rats. Rats were unilaterally implanted with an electrode
      into the lateral hypothalamus and trained to press a lever to obtain electrical
      brain stimulation. After stable responses had been established, the rats
      underwent six conditioning sessions with subcutaneous nicotine at 0.4 mg/kg in
      particular visual and tactile contexts. The threshold for electrical stimulation
      was then tested in either the nicotine-conditioned environment or novel
      environment under saline or nicotine treatment. Nicotine enhanced the responding
      for ICSS and significantly lowered the threshold in both environments. Under
      saline treatment, the responding for ICSS was facilitated and the threshold was
      significantly lower in the nicotine-conditioned environment than in the novel
      environment. The present results demonstrate that nicotine-conditioned contextual
      stimuli may affect the mesolimbic dopamine system through ICSS threshold lowering
      effect.

PMID- 22995978
TI  - Olfactory ability and object memory in three mouse models of varying body weight,
      metabolic hormones, and adiposity.
AB  - Physiological and nutritional state can modify sensory ability and perception
      through hormone signaling. Obesity and related metabolic disorders present a
      chronic imbalance in hormonal signaling that could impact sensory systems. In the
      olfactory system, external chemical cues are transduced into electrical signals
      to encode information. It is becoming evident that this system can also detect
      internal chemical cues in the form of molecules of energy homeostasis and
      endocrine hormones, whereby neurons of the olfactory system are modulated to
      change animal behavior towards olfactory cues. We hypothesized that chronic
      imbalance in hormonal signaling and energy homeostasis due to obesity would
      thereby disrupt olfactory behaviors in mice. To test this idea, we utilized three
      mouse models of varying body weight, metabolic hormones, and visceral adiposity -
      1) C57BL6/J mice maintained on a condensed-milk based, moderately high-fat diet
      (MHF) of 32% fat for 6 months as the diet-induced obesity model, 2) an obesity
      resistant, lean line of mice due to a gene-targeted deletion of a voltage
      dependent potassium channel (Kv 1.3-null), and 3) a genetic model of obesity as a
      result of a gene-targeted deletion of the melanocortin 4 receptor (MC4R-null).
      Diet-induced obese (DIO) mice failed to find a fatty-scented hidden peanut butter
      cracker, based solely on olfactory cues, any faster than an unscented hidden
      marble, initially suggesting general anosmia. However, when these DIO mice were
      challenged to find a sweet-scented hidden chocolate candy, they had no
      difficulty. Furthermore, DIO mice were able to discriminate between fatty acids
      that differ by a single double bond and are components of the MHF diet (linoleic
      and oleic acid) in a habituation-dishabituation paradigm. Obesity-resistant,
      Kv1.3-null mice exhibited no change in scented object retrieval when placed on
      the MHF-diet, nor did they perform differently than wild-type mice in parallel
      habituation-dishabituation paradigms of fatty food-related odor components.
      Genetically obese, MC4R-null mice successfully found hidden scented objects, but
      did so more slowly than lean, wild-type mice, in an object-dependent fashion. In
      habituation-dishabituation trials of general odorants, MC4R-null mice failed to
      discriminate a novel odor, but were able to distinguish two fatty acids. Object
      memory recognition tests for short- and long-term memory retention demonstrated
      that maintenance on the MHF diet did not modify the ability to perform these
      tasks independent of whether mice became obese or were resistant to weight gain
      (Kv1.3-null), however, the genetically predisposed obese mice (MC4R-null) failed
      the long-term object memory recognition performed at 24h. These results
      demonstrate that even though both the DIO mice and genetically predisposed obese
      mice are obese, they vary in the degree to which they exhibit behavioral deficits
      in odor detection, odor discrimination, and long-term memory.

PMID- 22995980
TI  - Early fracture stabilisation in the presence of subclinical hypoperfusion.
AB  - INTRODUCTION: In polytrauma patients with an injury severity score (ISS)>16,
      early long bone and pelvic fracture fixation within 24h after injury has been
      shown to be beneficial. In contrast, surgery in the presence of subclinical
      hypoperfusion (SCH), defined as normal vital signs with a serum
      lactate>=2.5mmol/L may be detrimental. This study aimed to investigate the effect
      of fracture fixation in polytrauma patients with SCH. METHODS: We undertook a
      database review extracting 88 polytrauma patients with a new injury severity
      score (NISS)>16 with significant long bone or pelvic fractures (extremity
      NISS>=9) who underwent surgical fracture stabilisation within 48h of injury. In
      the group of patients with normal vital signs (mean arterial pressure>=60mmHg and
      heart rate<=110 beats/min) we compared outcomes between those with a normal
      preoperative lactate (<2.5mmol/L) and those with a raised lactate (>=2.5mmol/L).
      RESULTS: Of the 36 patients with normal preoperative vital signs, 17 had normal
      lactates (control group) and 19 abnormal lactates (SCH group). There were no
      significant differences in the method of fixation or theatre time between the
      groups. The SCH group required more inotropic support in the first 24h post
      surgery (p=0.02) and had higher sequential organ failure assessment (SOFA) scores
      on day 3 (p=0.003). Although not reaching mathematical significance those with
      SCH required on average 10 days longer on mechanical ventilation. CONCLUSION:
      Early fracture fixation in patients with SCH as defined by normal vital signs and
      a lactate>=2.5mmol/L is associated with significant postoperative morbidity.
      Consideration should be given to delaying surgery in this cohort.

PMID- 22995981
TI  - Preoperative cardiac evaluation of geriatric patients with hip fracture.
AB  - BACKGROUND: The American College of Cardiology (ACC) and the American Heart
      Association (AHA) have developed guidelines for perioperative assessment of
      patients in case of non-cardiac surgery. The aim of this study was to investigate
      if the preoperative cardiac evaluation of geriatric patients with hip fracture
      was in accordance with these guidelines and what the effects were on outcome.
      METHODS: In a retrospective study 388 patients with hip fracture treated in the
      department of Trauma surgery of the Maastricht University Medical Centre in the
      Netherlands were included. All patients were treated between 2003 and 2006 and
      had at least two year follow-up. The preoperative cardiac screening was analysed
      with respect to content and to which level this followed the ACC/AHA guidelines.
      These guidelines were used to classify cardiac risk into low, intermediate and
      high risk. This was related to the outcome measurements delay to surgery,
      perioperative complications and mortality. RESULTS: According to the ACC/AHA
      guidelines 82% of patients received correct preoperative cardiac screening in the
      low vs. 46% in the intermediate and 86% in the high risk group. The most frequent
      reason for incorrect preoperative cardiac screening was overscreening (>95%). The
      delay to surgery increased by 9.9h in the case of overscreening (p=0.03). A
      previous cardiac history was a significant risk factor for early mortality. Delay
      of >48 h was associated with more cardiovascular complications and mortality both
      on univariate and multivariate analysis. CONCLUSION: Preoperative cardiac
      screening is frequently unnecessary after hip fracture, especially in patients
      with intermediate risk predictors and increases the delay to surgery. Delay of
      >48 h was associated with more cardiovascular complications and mortality
      postoperatively. The implementation of the ACC/AHA guidelines may prevent
      unnecessary cardiac consultations which reduces preoperative resources, delay to
      surgery and possibly decreases postoperative complications.

PMID- 22995982
TI  - Mortality from trauma in Scotland.

PMID- 22995983
TI  - Silicon-on-glass pore network micromodels with oxygen-sensing fluorophore films
      for chemical imaging and defined spatial structure.
AB  - Pore network microfluidic models were fabricated by a silicon-on-glass technique
      that provides the precision advantage of dry etched silicon while creating a
      structure that is transparent across all microfluidic channels and pores, and can
      be imaged from either side. A silicon layer is bonded to an underlying
      borosilicate glass substrate and thinned to the desired height of the
      microfluidic channels and pores. The silicon is then patterned and through-etched
      by deep reactive ion etching (DRIE), with the underlying glass serving as an etch
      stop. After bonding on a transparent glass cover plate, one obtains a micromodel
      in oxygen impermeable materials with water-wet surfaces where the microfluidic
      channels are transparent and structural elements such as the pillars creating the
      pore network are opaque. The advantageous features of this approach in a chemical
      imaging application are demonstrated by incorporating a Pt porphyrin fluorophore
      in a PDMS film serving as the oxygen-sensing layer and a bonding surface, or in a
      polystyrene film coated with a PDMS layer for bonding. The sensing of a dissolved
      oxygen gradient was demonstrated using fluorescence lifetime imaging, and it is
      shown that different matrix polymers lead to optimal use in different ranges of
      oxygen concentration. Imaging with the opaque pillars in between the observation
      direction and the continuous fluorophore film yields images that retain defined
      spatial structure in the sensor image.

PMID- 22995985
TI  - Indices of onchocerciasis transmission by different members of the Simulium
      damnosum complex conflict with the paradigm of forest and savanna parasite
      strains.
AB  - Onchocerciasis in savanna zones is generally more severe than in the forest and
      pathologies also differ geographically, differences often ascribed to the
      existence of two or more strains and incompatibilities between vectors and
      strains. However, flies in the forest transmit more infective larvae than their
      savanna counterparts, even in sympatry, contradicting expectations based on the
      forest and savanna strains paradigm. We analysed data on the numbers of
      Onchocerca volvulus larvae of different stages found in 10 different taxonomic
      categories of the Simulium damnosum complex derived from more than 48,800
      dissections of flies from Sierra Leone in the west of Africa to Uganda in the
      east. The samples were collected before widespread ivermectin distribution and
      thus provide a baseline for evaluating control measures. Savanna species
      contained fewer larvae per infected or per infective fly than the forest species,
      even when biting and parous rates were accounted for. The highest transmission
      indices were found in the forest-dwelling Pra form of Simulium sanctipauli (616
      L3/1000 parous flies) and the lowest in the savanna-inhabiting species S.
      damnosum/S. sirbanum (135) and S. kilibanum (65). Frequency distributions of
      numbers of L1-2 and L3 larvae found in parous S. damnosum/S. sirbanum, S.
      kilibanum, S. squamosum, S. yahense, S. sanctipauli, S. leonense and S. soubrense
      all conformed to the negative binomial distribution, with the mainly savanna
      dwelling species (S. damnosum/S. sirbanum) having less overdispersed
      distributions than the mainly forest-dwelling species. These infection patterns
      were maintained even when forest and savanna forms were sympatric and biting the
      same human population. Furthermore, for the first time, levels of blindness were
      positively correlated with infection intensities of the forest vector S. yahense,
      consistent with relations previously reported for savanna zones. Another novel
      result was that conversion rates of L1-2 larvae to L3s were equivalent for both
      forest and savanna vectors. We suggest that either a multiplicity of factors are
      contributing to the observed disease patterns or that many parasite strains exist
      within a continuum.

PMID- 22995984
TI  - [Patient safety in extra-hospital emergencies].
AB  - One of the biggest challenges for the public health sector is to ensure the
      clinical safety of the patient, which is affected by mistakes made in pre
      hospital emergency care. A culture of safety is encouraged and health
      professionals have tools at their disposal to help them maintain that safety.
      OBJECTIVE: [corrected] We propose as a hypothesis that compliance with safety
      standards in for the care of patients using extra-hospital emergency systems
      improves care and minimize risks. Our goal is to build a tool that enables us to
      measure the safety quality for patients in need of non-hospital emergency
      services. METHOD: To create this tool we have taken the SENECA study as a basis,
      and using the European Quality Model of the European Foundation of Quality
      Management (EFQM). The indicators were created using the Delphi Method. RESULTS:
      A total of 74 indicators were proposed, 9 of which were proposed by the
      panelists, and 44% being accepted. A definitive tool of 41 indicators was
      created. The most notable indicators were; "The expiry dates of consumable
      material and drugs that are stored in the units are controlled" grouped in
      "Alliances and resources", and "Patients who do not adhere to treatment due to
      unresolved doubts" grouped in "Key results". CONCLUSIONS: The use of the EFQM
      model to build the assessment tool allows information to be appropriately
      structured and to organize safety standards and indicators of security in a
      consistent manner. This methodology helped to propose a suitable tool for
      measuring patient safety in an extra-hospital situation. The application of this
      tool will identify areas for improvement related to the patient safety.

PMID- 22995986
TI  - Dynamic regulation of kinetochore-microtubule interaction during mitosis.
AB  - Chromosome segregation is carried out by dynamic interplay between kinetochores
      and microtubules. First, kinetochores are efficiently captured by microtubules.
      Then, flexible interactions between kinetochores and microtubules allow proper
      orientation of chromosomes aligned on the centre of the spindle. Finally,
      microtubules stably attached to kinetochores drag the chromosomes towards the
      spindle poles. During these processes, the mode of interaction of kinetochores
      with microtubules changes from lateral to end-on attachment, accompanied by
      changes in kinetochore structure/composition and microtubule dynamics. The
      molecular mechanisms for stable kinetochore-microtubule attachment have been
      progressively revealed in recent years. On the other hand, the mechanism of
      dynamic regulation of kinetochore-microtubule interaction in early mitosis, which
      is crucial for faithful chromosome segregation, continues to be elusive. Here I
      focus on this early step of chromosome segregation and discuss how kinetochores
      establish proper attachments to microtubules.

PMID- 22995987
TI  - The clinical relevance of rising CA-125 levels within the normal range in
      patients with uterine papillary serous cancer.
AB  - The utility of cancer antigen 125 (CA-125) levels as an adjunct method of
      monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial
      serous carcinoma after surgery and adjuvant treatment has been reported. Our goal
      was to determine the significance of rising CA-125 levels within the normal range
      in these patients in the posttreatment surveillance setting. All patients with
      UPSC who underwent surgical staging and had preoperative CA-125 measurement from
      1999 to 2008 were included in this analysis. Information was extracted from
      records to assess the changes in CA-125 values with clinical and/or radiographic
      detection of recurrence. Of the 56 evaluable patients, 23 (41%) recurred. Of the
      23 patients that recurred, 11 had serial CA-125 levels measured in remission.
      Elevated CA-125 levels at diagnosis were significantly associated with disease
      recurrence and advanced stage (P = .01, P = .001, respectively). The rise in CA
      125 by 10 U/mL in the normal range and >= 15 U/mL were associated with disease
      recurrence (P < .001, P < .001, respectively). In multivariate analysis, only CA
      125 level >= 15 U/mL was significantly associated with worse progression-free
      survival. In this small cohort of patients with recurrent UPSC after remission,
      surveillance of CA-125 levels may have a role in disease surveillance and
      management.

PMID- 22995988
TI  - Fibroid-associated heavy menstrual bleeding: correlation between clinical
      features, Doppler ultrasound assessment of vasculature, and tissue gene
      expression profiles.
AB  - Despite the prevalence of uterine fibroids (Fs), few studies have investigated
      the links between clinical features and the cellular or molecular mechanisms that
      drive F growth and development. Such knowledge will ultimately help to
      differentiate symptomatic from asymptomatic Fs and could result in the
      development of more effective and individualized treatments. The aim of this
      study was to investigate the relationship between ultrasound appearance, blood
      flow, and angiogenic gene expression in F, perifibroid (PM), and distant
      myometrial (DM) tissues. We hypothesized that angiogenic gene expression would be
      increased in tissues and participants that showed increased blood flow by Doppler
      ultrasound. The study was performed using Doppler ultrasound to measure blood
      flow prior to hysterectomy, with subsequent tissue samples from the F, PM, and DM
      being investigated for angiogenic gene expression. Overall, PM blood flow
      (measured as peak systolic velocity [PSV]) was higher than F blood flow, although
      significant heterogeneity was seen in vascularity and blood flow between
      different Fs and their surrounding myometrium. We did not find any correlation
      between PSV and any other clinical or molecular parameter in this study. We
      identified 19 angiogenesis pathway-related genes with significant differences in
      expression between F and DM, and 2 genes, matrix metalloproteinase 9 (MMP9) and
      Neuropilin 2 (NRP2), that were significantly different between F and PM. These
      results are consistent with subtle differences between PM and DM. Understanding
      the differences between symptomatic versus asymptomatic Fs may eventually lead to
      more effective treatments that directly target the source of heavy menstrual
      bleeding.

PMID- 22995989
TI  - Complex genetics of radial ray deficiencies: screening of a cohort of 54
      patients.
AB  - PURPOSE: Radial ray deficiencies are characterized by unilateral or bilateral
      absence of varying portions of the radius and thumb. Both isolated and syndromic
      forms have been described, and although for some of the syndromes the causal gene
      has been identified, many patients remain without a genetic diagnosis. METHODS:
      In this study, a cohort of 54 patients with radial ray deficiencies was screened
      for genomic aberrations by molecular karyotyping. RESULTS: In 8 of 54 cases, an
      aberration was detected. Two unrelated patients inherited a 1q21.1
      microduplication from a healthy parent, whereas in a third patient, a 16p13.11
      microduplication was identified. Two other interesting microdeletions were
      detected: a 10q24.3 deletion at the split hand-foot malformation (SHFM3) locus
      and a 7p22.1 deletion including the RAC1 gene. CONCLUSION: The finding of these
      microduplications may just be coincidental or, alternatively, they may illustrate
      the broad phenotypic spectrum of these microduplications. Duplications in the
      10q24.3 region result in split hand-foot malformations, and our observation
      indicates that deletions may cause radial ray defects. Finally, a candidate gene
      for radial ray deficiencies was detected in the 7p22.1 deletion. RAC1 plays an
      important role in the canonical Wnt pathway and conditional RAC1 knockout mice
      exhibit truncated-limb defects.

PMID- 22995990
TI  - Behavioral genetics and population health interventions for alcohol problems: at
      odds or oddly in agreement?

PMID- 22995991
TI  - An informatics approach to analyzing the incidentalome.
AB  - PURPOSE: Next-generation sequencing has transformed genetic research and is
      poised to revolutionize clinical diagnosis. However, the vast amount of data and
      inevitable discovery of incidental findings require novel analytic approaches. We
      therefore implemented for the first time a strategy that utilizes an a priori
      structured framework and a conservative threshold for selecting clinically
      relevant incidental findings. METHODS: We categorized 2,016 genes linked with
      Mendelian diseases into "bins" based on clinical utility and validity, and used a
      computational algorithm to analyze 80 whole-genome sequences in order to explore
      the use of such an approach in a simulated real-world setting. RESULTS: The
      algorithm effectively reduced the number of variants requiring human review and
      identified incidental variants with likely clinical relevance. Incorporation of
      the Human Gene Mutation Database improved the yield for missense mutations but
      also revealed that a substantial proportion of purported disease-causing
      mutations were misleading. CONCLUSION: This approach is adaptable to any
      clinically relevant bin structure, scalable to the demands of a clinical
      laboratory workflow, and flexible with respect to advances in genomics. We
      anticipate that application of this strategy will facilitate pretest informed
      consent, laboratory analysis, and posttest return of results in a clinical
      context.

PMID- 22995993
TI  - Wearing knee wraps affects mechanical output and performance characteristics of
      back squat exercise.
AB  - The aim of this study was to investigate the effects of wearing knee wraps on
      mechanical output and performance characteristics of back squat exercise. Ten
      resistance trained men (back squat 1 repetition maximum [1RM]: 160.5 +/- 18.4 kg)
      performed 6 single back squats with 80% 1RM, 3 wearing knee wraps, 3 without.
      Mechanical output was obtained from ground reaction force, performance
      characteristics from digitized motion footage obtained from a single high-speed
      digital camera. Wearing knee wraps led to a 39% reduction (0.09 compared with
      0.11 m, p = 0.037) in horizontal barbell displacement that continued during the
      lifting phase. Lowering phase vertical impulse remained within 1% across
      conditions; however, the lowering phase was performed 45% faster (1.13 compared
      with 1.57 seconds). This demonstrated that vertical force applied to the center
      of mass during the lowering phase was considerably larger and was likely a
      consequence of the generation and storage of elastic energy within the knee wrap.
      Subsequent vertical impulse applied to the center of mass was 10% greater (192
      compared with 169 N.s, p = 0.018). Mechanical work involved in vertically
      displacing the center of mass was performed 20% faster and was reflected by a 10%
      increase in peak power (2,121 compared with 1,841 W, p = 0.019). The elastic
      properties of knee wraps increased mechanical output but altered back squat
      technique in a way that is likely to alter the musculature targeted by the
      exercise and possibly compromise the integrity of the knee joint. Knee wraps
      should not be worn during the strength and condition process, and perceived
      weakness in the knee joint should be assessed and treated.

PMID- 22995994
TI  - Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age
      related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in
      developed countries for people over the age of 50. In this work, the dosimetric
      feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance
      kilovoltage stereotactic radiosurgery for neovascular AMD is investigated.
      Microdosimetry calculations at the sub-cellular level were carried out to
      estimate the radiation dose enhancement to individual nuclei in neovascular AMD
      endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray
      irradiated AuNP. The nDEF represents the ratio of radiation doses to the
      endothelial cell nuclei with and without AuNP. The calculations were carried out
      for a range of feasible AuNP local concentrations using the clinically applicable
      100 kVp x-ray beam parameters employed by a commercially available x-ray therapy
      system. The results revealed nDEF values of 1.30-3.26 for the investigated
      concentration range of 1-7 mg g(-1), respectively. In comparison, for the same
      concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12
      were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile,
      calculations as a function of distance from the AuNP showed that the dose
      enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD
      endothelial cells where AuNP are localized. These findings provide impetus for
      considering the application of AuNP to enhance therapeutic efficacy during
      stereotactic radiosurgery for neovascular AMD.

PMID- 22995995
TI  - Effect of body size on organ-specific mitochondrial respiration rate of the
      largemouth bronze gudgeon.
AB  - The effects of body size on the mitochondrial respiration rate were assessed in
      the heart, brain, gill, liver, and red muscle of largemouth bronze gudgeon,
      Coreius guichenoti, from the Yangtze River. Body mass had a significant influence
      on the state 3 oxygen consumption rate of the mitochondria from the heart, gill,
      and red muscle. The relationships between body mass (M, g) and state 3 oxygen
      consumption rate (V(state 3), nmol O min(-1) mg(-1)) of the mitochondria were
      represented by the following: V(state 3) = 3.56M(0.71) for heart, V(state 3) =
      4.64M(0.50) for red muscle, and V(state 3) = 473.73M(-0.82) for gill. There was a
      significant difference in V(state 3), V(state 4), and respiratory control ratio
      among organs and all were highest in the heart. Our results suggest that the
      relationship between mitochondrial respiratory rate and body size varies among
      organs. The high mitochondrial respiratory rate in the heart of the largemouth
      gudgeon suggests that it has the highest oxidative capacity.

PMID- 22995996
TI  - A tag-less method for direct isolation of human umbilical vein endothelial cells
      by gravitational field-flow fractionation.
AB  - The analysis of cellular and molecular profiles represents a powerful tool in
      many biomedical applications to identify the mechanisms underlying the
      pathological changes. The improvement of cellular starting material and the
      maintenance of the physiological status in the sample preparation are very
      useful. Human umbilical vein endothelial cells (HUVEC) are a model for prediction
      of endothelial dysfunction. HUVEC are enzymatically removed from the umbilical
      vein by collagenase. This method provides obtaining a good sample yield. However,
      the obtained cells are often contaminated with blood cells and fibroblasts.
      Methods based on negative selection by in vitro passages or on the use of defined
      marker are currently employed to isolate target cells. However, these approaches
      cannot reproduce physiological status and they require expensive instrumentation.
      Here we proposed a new method for an easy, tag-less and direct isolation of HUVEC
      from raw umbilical cord sample based on the gravitational field-flow
      fractionation (GrFFF). This is a low-cost, fully biocompatible method with low
      instrumental and training investments for flow-assisted cell fractionation. The
      method allows obtaining pure cells without cell culture procedures as starting
      material for further analysis; for example, a proper amount of RNA can be
      extracted. The approach can be easily integrated into clinical and biomedical
      procedures.

PMID- 22995997
TI  - Determination of bisphenol A and bisphenol B in canned seafood combining QuEChERS
      extraction with dispersive liquid-liquid microextraction followed by gas
      chromatography-mass spectrometry.
AB  - A new simple and reliable method combining an acetonitrile partitioning
      extractive procedure followed by dispersive solid-phase cleanup (QuEChERS) with
      dispersive liquid-liquid microextraction (DLLME) and further gas chromatography
      mass spectrometry analysis was developed for the simultaneous determination of
      bisphenol A (BPA) and bisphenol B (BPB) in canned seafood samples. Besides the
      great enrichment factor provided, the final DLLME extractive step was designed in
      order to allow the simultaneous acetylation of the compounds required for their
      gas chromatographic analysis. Tetrachloroethylene was used as extractive solvent,
      while the acetonitrile extract obtained from QuEChERS was used as dispersive
      solvent, and anhydride acetic as derivatizing reagent. The main factors
      influencing QuEChERS and DLLME efficiency including nature of QuEChERS dispersive
      SPE sorbents, amount of DLLME extractive and dispersive solvents and nature and
      amount of derivatizing reagent were evaluated. DLLME procedure provides an
      effective enrichment of the extract, allowing the required sensitivity even using
      a single quadropole MS as detector. The optimized method showed to be accurate
      (>68 % recovery), reproducible (<21 % relative standard deviation) and sensitive
      for the target analytes (method detection limits of 0.2 MUg/kg for BPA and 0.4
      MUg/kg for BPB). The screening of several canned seafood samples commercialized
      in Portugal (total = 47) revealed the presence of BPA in more than 83 % of the
      samples with levels ranging from 1.0 to 99.9 MUg/kg, while BPB was found in only
      one sample at a level of 21.8 MUg/kg.

PMID- 22995998
TI  - Recent advances in the design of organic polymer monoliths for reversed-phase and
      hydrophilic interaction chromatography separations of small molecules.
AB  - Owing to their favorable porous structure with pore size distribution shifted
      towards large flow-through pores, organic polymer monoliths have been mainly
      employed for the separation of macromolecules in gradient elution liquid
      chromatography. The absence of significant amounts of small pores with a stagnant
      mobile phase and the resulting low surface area were considered as the main
      reason for their poor behavior in the isocratic separation of small molecules.
      Several recent efforts have improved the separation power of organic polymer
      monoliths for small molecules offering column efficiency up to tens of thousands
      of plates per meter. These attempts include optimization of the composition of
      polymerization mixture, including the variation of functional monomer, the cross
      linking monomer, and the porogen solvents mixture, adjustment of polymerization
      temperature, and time. Additionally, post-polymerization modifications including
      hypercross-linking and the use of carbon nanostructures showed significant
      improvement in the column properties. This review describes recent developments
      in the preparation of organic polymer monoliths suitable for the separation of
      small molecules in the isocratic mode as well as the main factors affecting the
      column efficiency.

PMID- 22995999
TI  - Microalgal motility measurement microfluidic chip for toxicity assessment of
      heavy metals.
AB  - A polydimethylsiloxane microfluidic chip has been developed for the estimation of
      toxic heavy metals based on measurement of mobility of marine microalgae. The
      chip is mainly composed of an upstream concentration gradient generator and a
      downstream perfusion-based chemotatic module. The processes of toxic liquid
      dilution and diffusion, microalgal culturing, cell stimulation, and online
      screening can be integrated in this chip, which makes it an attractive approach
      to simplify toxicity testing procedures. The microalgal motility was adopted as a
      microfluidic bioassay signal and was evaluated as the percentage of motile cells,
      curvilinear velocity, average path velocity, and straight line velocity. Two
      mobile marine microalgae, Platymonas subcordiformis and Platymonas helgolandica
      var. tsingtaoensis, were confined in the chemotatic module and stimulated by the
      eight concentration gradients of Cu and Cd generated by the concentration
      gradient generator. In all cases, a toxic response was detected (i.e., a dose
      related inhibition of motility was observed). Only 1.5 h was needed to predict
      EC(50) values. Thus, the microfluidic chip developed was proved to be useful as a
      simple and rapid approach in heavy metal detection and might be expanded as a
      conventional test method in environmental toxicity assessment.

PMID- 22996000
TI  - Stochastic analyses to identify wellfield withdrawal effects on surface-water and
      groundwater in Miami-Dade County, Florida.
AB  - Several stochastic analyses were conducted in Miami-Dade County, Florida, to
      evaluate the effects of wellfield withdrawal on aquifer water levels, canal
      stage, and canal flow. Multiyear data for withdrawals at four water-supply
      wellfields, water levels at the S-121 canal control structure and groundwater
      head at a nearby monitoring well were used to determine the interrelation between
      wellfield withdrawals and water levels in the canal and aquifer. A spectral
      analysis was performed first on the wellfield withdrawals, showing similar
      patterns of fluctuations, but no well-defined seasonality. In order to compare
      water-level response with withdrawals at each wellfield, the intercorrelation
      effects between wellfields was removed through a 'causal chain' approach where
      the inter-wellfield correlation is used to isolate the wellfield/water-level
      correlation. Most computed correlations have magnitudes less than 5 percent, but
      with statistical significance above 90 percent. Results indicate that withdrawals
      from the wellfields most distant from the canal had no significant correlation to
      the canal levels. However the highest correlation was not at the wellfield
      closest to the canal, but at the two wellfields at the intermediate distance that
      have higher withdrawal rates. The hydraulic interconnectivity of the canal with
      the rest of the canal network, covering the study area, allows the canal
      equalizes with all connected canals. This explains why proximity to a particular
      canal location does not appear to be as important a factor as the withdrawal
      rate. Groundwater levels are more highly correlated to a wellfield on the same
      side of the canal, and to pumping wells in the same wellfield on the same side of
      the canal. This indicates that canals are an effective barrier and source/sink
      for the groundwater. Further nonlinear correlation analysis indicates that high
      withdrawal rates disproportionally affect water levels and are the predominant
      effect on the canal.

PMID- 22996001
TI  - Assessing biodiversity on the farm scale as basis for ecosystem service payments.
AB  - Ecosystem services payments must be based on a standardised transparent
      assessment of the goods and services provided. This is especially relevant in the
      context of EU agri-environmental programs, but also for organic-food companies
      that foster environmental services on their contractor farms. Addressing the farm
      scale is important because land users/owners are major recipients of payments and
      they could be more involved in data generation and conservation management. A
      standardised system for measuring on-farm biodiversity does not yet exist that
      concentrates on performance indicators and includes farmers in generating
      information. A method is required that produces ordinal or metric scaled
      assessment results as well as management measures. Another requirement is the
      ease of application, which includes the ease of gathering input data and
      understandability. In order to respond to this need, we developed a method which
      is designed for automated application in an open source farm assessment system
      named MANUELA. The method produces an ordinal scale assessment of biodiversity
      that includes biotopes, species, biotope connectivity and the influence of land
      use. In addition, specific measures for biotope types are proposed. The open
      source geographical information system OpenJump is used for the implementation of
      MANUELA. The results of the trial applications and robustness tests show that the
      assessment can be implemented, for the most part, using existing information as
      well as data available from farmers or advisors. The results are more sensitive
      for showing on-farm achievements and changes than existing biotope-type
      classifications. Such a differentiated classification is needed as a basis for
      ecosystem service payments and for designing effective measures. The robustness
      of the results with respect to biotope connectivity is comparable to that of
      complex models, but it should be further improved. Interviews with the test
      farmers substantiate that the assessment methods can be implemented on farms and
      they are understood by farmers.

PMID- 22996002
TI  - Modeling riverine pathogen fate and transport in Mexican rural communities and
      associated public health implications.
AB  - The discharge of untreated or poorly treated wastewater to river systems remains
      a major problem affecting public and environmental health, particularly in rural
      communities of less developed countries. One of the primary goals in setting
      policies for wastewater management is to reduce risks to human health associated
      with microbial contamination of receiving water. In this study, we apply a
      surface water quality model to develop an Escherichia coli based indicator that
      reflects the quality of surface water and the potential impact to recreational
      users in a large, rural river in northwest Mexico (upper Sonora River). The model
      assesses the relative importance of streamflow variations and the uncertainty in
      E. coli removal coefficient parameters for the predictions of E. coli
      concentrations in the river. Given the sparse information on streamflow, we use a
      physically-based, distributed hydrologic model to generate tributary
      contributions to the river. We determined the best estimate and uncertainty of E.
      coli removal rates to explore the impacts of parameter uncertainty on the
      transport of E. coli downstream from two wastewater discharge zones. Our results
      depict the regions in the river that are in noncompliance with fresh water
      pathogen norms. The impact of streamflow variability and uncertainty in the
      removal rates of pathogen indicators was used to derive a range of river
      distances in noncompliance. The comparison between two sites with different
      streamflow behaviors was used to illustrate the impacts of streamflow
      spatiotemporal variability on pathogen indicators. We derive a simple
      relationship that can be used to assess the relative importance of dilution
      (ratio of wastewater discharge to river discharge) and pathogen removal (ratio of
      residence time to reaction time).

PMID- 22996003
TI  - COD fractionation and biological treatability of mixed industrial wastewaters.
AB  - This study was conducted at a centralized wastewater treatment plant that
      receives discharges from nearly 160 industries. The chemical oxygen demand (COD)
      was fractionated for two objectives: delineation of the limits of the activated
      sludge process being used at the plant, and evaluation of the potential
      environmental impact of the treated effluent. Physico-chemical analyses,
      respirometric and biodegradation tests, as well as COD fractionation were carried
      out. Molasses-wastewaters were determined to be the major contribution to the
      plant. The influent was dark brown in color, with a relatively high content of
      both organics (2503 mg/L COD) and salts (5459 MUS/cm conductivity), but a low
      biochemical oxygen demand (568 mg/L BOD(5)) and BOD(5)/COD ratio (0.24). The
      degradability of the organics was limited by the high content of inert soluble
      COD (S(I)). The COD fractionation pattern was 40-20-40% for S(I), X(I) (inerts)
      and S(H) (soluble hydrolyzable), respectively. More than 90% BOD(5) removal was
      obtained, which was sufficient for the plant to meet the national Standards.
      However, the effluent discharged into the river was intensely colored and
      polluted (>1000 mg/L COD, >5000 MUS/cm), emphasizing the need for legislation
      regulating COD, color and salinity, and for upgraded treatment methods worldwide
      for molasses wastewaters.

PMID- 22996004
TI  - Impact of pig slurry amendments on phosphorus, suspended sediment and metal
      losses in laboratory runoff boxes under simulated rainfall.
AB  - Losses of phosphorus (P) when pig slurry applications to land are followed by a
      rainfall event or losses from soils with high P contents can contribute to
      eutrophication of receiving waters. The addition of amendments to pig slurry
      spread on high P Index soils may reduce P and suspended sediment (SS) losses.
      This hypothesis was tested at laboratory-scale using runoff boxes under simulated
      rainfall conditions. Intact grassed soil samples, 100 cm-long, 22.5 cm-wide and 5
      cm-deep, were placed in runoff boxes and pig slurry or amended pig slurry was
      applied to the soil surface. The amendments examined were: (1) commercial grade
      liquid alum (8% Al(2)O(3)) applied at a rate of 0.88:1 [Al:total phosphorus (TP)]
      (2) commercial-grade liquid ferric chloride (38% FeCl(3)) applied at a rate of
      0.89:1 [Fe:TP] and (3) commercial-grade liquid poly-aluminium chloride (PAC) (10%
      Al(2)O(3)) applied at a rate of 0.72:1 [Al:TP]. The grassed soil was then
      subjected to three rainfall events (10.3 +/- 0.15 mm h(-1)) at time intervals of
      48, 72, and 96 h following slurry application. Each sod received rainfall on 3
      occasions. Results across three rainfall events showed that for the control
      treatment, the average flow weighted mean concentration (FWMC) of TP was 0.61 mg
      L(-1), of which 31% was particulate phosphorus (PP), and the average FWMC of SS
      was 38.1 mg L(-1). For the slurry treatment, there was an average FWMC of 2.2 mg
      TP L(-1), 47% of which was PP, and the average FWMC of SS was 71.5 mg L(-1).
      Ranked in order of effectiveness from best to worst, PAC reduced the average FWMC
      of TP to 0.64 mg L(-1) (42% PP), FeCl(3) reduced TP to 0.91 mg L(-1) (52% PP) and
      alum reduced TP to 1.08 mg L(-1) (56% PP). The amendments were in the same order
      when ranked for effectiveness at reducing SS: PAC (74%), FeCl(3) (66%) and alum
      (39%). Total phosphorus levels in runoff plots receiving amended slurry remained
      above those from soil only, indicating that, although incidental losses could be
      mitigated by chemical amendment, chronic losses from the high P index soil in the
      current study could not be reduced.

PMID- 22996005
TI  - Phytoremediation of explosives (TNT, RDX, HMX) by wild-type and transgenic
      plants.
AB  - The large-scale production and processing of munitions has led to vast
      environmental pollution by the compounds TNT(2,4,6-trinitrotoluene),
      RDX(hexahydro-1,3,5-trinitro-1,3,5-triazine) and HMX(octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetrazocine). Explosives contain these toxic and mutagenic xenobiotics,
      which are stable in the environment and recalcitrant to remediation. Certain
      technologies used thus far (incineration, adsorption, advanced oxidations
      processes, chemical reduction etc.) have not only been very expensive but also
      caused additional environmental problems. During recent decades, the most popular
      technologies have been biotechnological methods, such as phytoremediation, which
      is relatively cheap, environmentally friendly, and a highly accepted solution by
      society. The most promising of these technologies is the usage of genetically
      modified plants, which combines the ability of bacterial genes to detoxify
      compounds with the phytoremediation benefits of plants. This paper is a review
      related to the latest and most important achievements in the field of
      phytoremediation of water and soil contaminated with TNT, RDX and HMX.

PMID- 22996006
TI  - A modeling approach toward oil spill management along the Eastern Mediterranean.
AB  - This paper examines the temporal and spatial distributions of the largest oil
      spill along the Eastern Mediterranean and explores management options (boom
      deployment and fuel upgrade) to reduce potential adverse impacts on the marine
      environment from similar accidents. For this purpose, the trajectory and
      weathering of the ~18,000 tons of heavy fuel oil spilled from the Jiyeh thermal
      power plant were simulated along the coast of Lebanon using the 3D MEDSLIK model,
      supported with sea water sampling and analysis and field measurements. The base
      simulation of the spill under existing conditions at the time of occurrence
      defined the temporal distribution over 90 days of oil spilled in terms of
      percentage of oil on the surface or evaporated (13.1%), dispersed in the water
      column or landed on the coast (86.9% landed of which 30.1% were potentially
      releasable). The spatial distribution defined shoreline stretches with high risk
      of exposure (located 35 km north of the source and stretching for more than 150
      km with medium to low risk exposure). Parametric analysis revealed a relatively
      higher sensitivity to the drift factor, the current depth, and the time of spill
      parameters. Deployment of booms reduced shorelines exposure by ~95% in comparison
      to baseline conditions, and medium or light brands increased evaporation by ~22
      42% and reduced oil reaching the coast by ~37-57% in comparison to heavy fuel
      oil.

PMID- 22996007
TI  - Subtype distribution of Blastocystis isolates identified in a Sydney population
      and pathogenic potential of Blastocystis.
AB  - Blastocystis is one of the most common enteric parasites present in humans. There
      is still much uncertainty about the pathogenic potential of this parasite, and it
      was suggested that its pathogenicity could be subtype-related. This report aimed
      to study 98 Blastocystis isolates found in human stool specimens to identify the
      subtypes present and carry out phylogenetic analysis on these isolates. This
      study also aimed to show the relationship between subtype and symptoms. Five
      hundred and thirteen stool samples were submitted to five different diagnostic
      techniques for the detection of Blastocystis. Polymerase chain reaction (PCR)
      positive samples were then sequenced and the small subunit (SSU) rDNA sequences
      were aligned and submitted to phylogenetic analysis. Ninety-eight samples were
      positive by any of the diagnostic methods for Blastocystis and 96 were positive
      by PCR. There were seven different subtypes (1, 2, 3, 4, 6, 7 and 8) identified
      by PCR and sequencing. This is the first large-scale study to examine the
      occurrence of Blastocystis in Australia. This study reports the high incidence of
      subtype 3 (44 %) in this population and discusses the emerging idea of subtype
      dependent pathogenicity.

PMID- 22996012
TI  - Preoperative fat-free mass: a predictive factor of weight loss after gastric
      bypass.
AB  - Weight loss failure occurs in 8% to 40% of patients after gastric bypass (GBP).
      The aim of our study was to analyse the predictive factors of weight loss at 1
      year so as to select the best candidates for this surgery and reduce the
      failures. We included 73 patients treated by laparoscopic GBP. We retrospectively
      analysed the predictive factors of weight loss in kilograms as well as excess
      weight loss in percentage (EWL%) at 1 year. The population was divided into
      tertiles so as to compare the sub-group with the highest weight loss with the sub
      group with the least satisfactory results. The significantly predictive factors
      of a better weight loss in kilograms were male, higher initial weight (144 versus
      118 kg, p = 0.002), a significant early weight loss and a higher preoperative
      percentage of fat-free mass (FFM%; p = 0.03). A higher FFM% was also associated
      with a better EWL% (p = 0.004). The preoperative FFM (in kilograms) was the
      principal factor accounting for the weight loss at 1 year regardless of age,
      gender, height and initial body mass index (BMI; p < 0.0001). There was a better
      correlation between FFM and weight loss (Spearman test, p = 0.0001) than between
      initial BMI and weight loss (p = 0.016). We estimated weight loss at 1 year
      according to initial FFM using the formula: 0.5 kg of lost weight per kilogram of
      initial FFM. The initial FFM appears to be a decisive factor in the success of
      GBP. Thus, the sarcopoenic patients would appear to be less suitable candidates
      for this surgery.

PMID- 22996013
TI  - Neurotoxic effects of bisphenol AF on calcium-induced ROS and MAPKs.
AB  - Bisphenol AF (BPAF), a newly introduced chemical structurally related to
      bisphenol A, is used extensively in fluoroelastomers and polyesters, and has been
      known to induce estrogen-dependent responses. However, the toxicity of BPAF is
      largely unknown except for its endocrine-related effects. In this study, we
      investigated the neurotoxicity of BPAF and underlying mechanisms of action using
      hippocampal cell line (HT-22) and mouse primary neuronal cells. We found that
      BPAF induced apoptosis in both HT-22 and primary neuronal cells. In order to
      clarify the underlying mechanisms of BPAF-induced apoptosis, various signaling
      molecules were evaluated. BPAF increased the level of intracellular calcium,
      followed by the generation of reactive oxygen species (ROS). BPAF upregulated the
      phosphorylation of mitogen-activated protein kinase: extracellular signal
      regulated kinase, p38 and c-Jun N-terminal kinase (JNK), and nuclear
      translocation of nuclear factor-kappaB. Using specific inhibitors, we confirmed
      that calcium, ROS, p38, and JNK mediated the BPAF-induced apoptosis. In addition,
      BPAF inhibited microglial activation in a microglia/neuroblastoma coculture model
      by the reduction of nitric oxide production. We found that BPAF interrupted the
      normal physiologic functions of microglia at non-toxic levels. Taken together,
      our results suggest that BPAF, the substitute of BPA, also have neurotoxic
      properties.

PMID- 22996014
TI  - New prognosis biomarkers identified by dynamic proteomic analysis of colorectal
      cancer.
AB  - The initiation, promotion and progression of human cancer are complex, polygenic,
      multi-factored processes. Through systematic proteomic analysis, different stages
      of CRC (colorectal cancer) biopsies were examined, and 199 differentially
      expressed proteins were detected between TNM (the tumor, nodes, and metastasis)
      stages I-IV and normal tissue (One-Way Analysis of Variance, ANOVA; p<= 0.05).
      Instead of looking for biomarkers to distinguish CRC from normal or identify
      metastatic tumors, we focused on the variation tendency of CRC carcinogenesis and
      the dynamic expression patterns of proteins among the different stages. Som (self
      organizing map clustering) analysis revealed eight unique expression patterns and
      that the cancer-related proteins were dynamically expressed, and their expression
      levels changed continuously throughout tumorigenesis. Molecular evidence emerged
      much earlier than visible, clinical or histological changes, which shows the
      potential prospect of building molecular staging. Proteins identified by MALDI
      TOF MS (Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass
      Spectrometry) were mainly involved in energy metabolism, acetylation and
      signaling pathways. Validation experiments using immunoblotting and
      immunohistochemistry (IHC) agreed with the 2D-DIGE (two-dimensional difference in
      gel electrophoresis) data. After survival classifier and LOOCV (leave-one-out
      cross-validation) analyses, the new prognostic biomarkers (78 kDa Glucose
      Regulated Protein precursor (GRP78), Fructose-bisphosphate Aldolase A (ALDOA),
      Carbonic Anhydrase I (CA1) and Peptidyl-prolyl cis-trans isomerase A or
      Cyclophilin A (PPIA)) provided good survival prediction for TNM stage I-IV
      patients. The new biomarkers derived from the dynamic patterns of these proteins'
      expression provide is a good supplementary method for determining prognosis for
      CRC, especially for the TNM stage III and IV patients.

PMID- 22996015
TI  - Long-term survival in thymic epithelial tumors: a single-center experience from
      China.
AB  - BACKGROUND: To evaluate long-term survival in thymic epithelial tumors (TETs), we
      present our experiences at a single institution in China. METHODS: We performed a
      retrospective analysis including 115 patients with TETs from 2001 to 2006.
      Histological diagnosis was completed based on the new WHO classification system.
      A univariate and multivariate survival analysis was performed, which included
      myasthenia gravis (MG), WHO histological type, Masaoka stage, completeness of
      resection, and adjuvant radiotherapy (RT). RESULTS: WHO histological subtype was
      closely correlated with that of Masaoka stage. The overall median survival time
      was 84.4 months and the 7-year survival rate was 78%. In the univariate analysis,
      three prognostic factors, including WHO histology type, Masaoka stage and
      complete resection, were statistically significant. In the analysis of the cases
      with complete resection, adjuvant RT did not show obvious survival benefit. In
      the multivariate analysis, Masaoka stage was the only independent factor that
      predicted long-time survival. CONCLUSIONS: Thymic carcinoma should be regarded as
      a different category of the disease due to its aggressive and poorer prognosis.
      Complete resection of the tumor and Masaoka stage I and II were found to
      contribute to a better survival. Adjuvant RT is not recommended for patients with
      complete resection in thymomas.

PMID- 22996016
TI  - Autoregulation of Sec7 Arf-GEF activity and localization by positive feedback.
AB  - Members of the highly conserved Arf family of small GTPases serve as master
      regulators of vesicular transport. In yeast, Arf1 acts at the Golgi and trans
      Golgi network (TGN) to recruit vesicular coat proteins and other effectors for
      both anterograde and retrograde transport. Arf1 is activated at the TGN by Sec7,
      the founding member of the Sec7 family of guanine nucleotide exchange factors
      (GEFs) and a close homolog of the human ARFGEF2 implicated in congenital defects
      in cerebral cortex development. Through the use of purified Sec7 in biochemical
      assays, we recently discovered that autoinhibition of Sec7 is relieved by stable
      recruitment to lipid membranes by activated Arf1. This interaction is mediated by
      a conserved domain proximal to, but not including, the GEF domain, creating a
      positive feedback loop in the activation of Arf1 at the TGN. We further
      demonstrated that this stable interaction with Arf1 plays a role in localizing
      Sec7 to the TGN. We elaborate here on the implications of these results to small
      GTPase-mediated cellular processes and coincidence detection models of GEF
      localization.

PMID- 22996017
TI  - Body mass normalization for isometric tests of muscle endurance.
AB  - The primary purpose of this study was to derive allometric parameters for
      normalizing Biering-Sorensen and Plank Test scores (measures of isometric back
      and abdominal muscle endurance, respectively) to body mass. The secondary purpose
      was to determine if allometric scaling with derived allometric parameters or the
      theoretical allometric parameter (b = -0.33) is the more appropriate method for
      normalizing Biering-Sorensen and Plank Test scores to body mass. A sample of 83
      male career firefighters (age = 35.7 +/- 9.4 years; body mass = 89.5 +/- 14.8 kg)
      participated in this study. Significant correlations were found between body mass
      and test scores (Biering-Sorensen Test: r = -0.36, p = 0.001; Plank Test: r = 
      0.55, p < 0.001). Derived allometric parameters for Biering-Sorensen and Plank
      Tests were b = -0.932 and -1.369, respectively. Allometric scaling with the
      derived allometric parameters was deemed appropriate at normalizing Biering
      Sorensen and Plank Test scores because it caused the correlations between body
      mass and test scores to become insignificant (Biering-Sorensen Test: r = 0.10, p
      = 0.354; Plank Test: r = 0.14, p = 0.173). Allometric scaling with the
      theoretical allometric parameter was deemed inappropriate for normalizing Biering
      Sorensen and Plank Test scores because it was not robust enough to get rid of the
      significant correlations between body mass and test scores (Biering-Sorensen
      Test: r = -0.23, p = 0.034; Plank Test: r = -0.43, p < 0.001). Allometric scaling
      with derived allometric parameters should be used to normalize Biering-Sorensen
      and Plank Test scores to body mass, particularly when attempting to account for
      changes in body mass across time intervals and differences in body mass across
      individuals.

PMID- 22996018
TI  - Effect of supportive equipment on force, velocity, and power in the squat.
AB  - The purpose of this investigation was to examine various kinetic and kinematic
      variables associated with squats without and with the use of a squat suit (SS).
      No previous investigation has examined the effect of an SS on squat performance.
      Participants were 8 elite or professional level male powerlifters (height =
      178.59 +/- 3.5 cm; body mass = 106.8 +/- 30.4 kg; age = 25 +/- 2.2 years; mean 1
      repetition maximum [1RM] =197.7 +/- 53 kg). Subjects participated in 3 testing
      sessions, with the first session involving a 1RM squat without a squat suit
      (NSS). Sessions 2 and 3 involved a testing session completing 2 trials in the
      squat at 3 intensities (80, 90, and 100% of 1RM) either without (NSS) or with an
      SS. The session and order of the intensities were all randomized. Force-time,
      velocity-time, and power-time graphs were calculated from data from a force plate
      and 2 linear position transducers attached to the barbell. Peak eccentric force
      was significantly higher during SS at 100% of 1RM (NSS-100 = 3196.2 +/- 470.6, SS
      100 = 3369.7 +/- 589.9 N). Peak concentric velocity was significantly higher
      during SS in comparison to NSS at all intensities. Peak concentric power was
      significantly higher during SS at 80% of 1RM (NSS-80 = 1566.5 +/- 388.4 W, SS-80
      = 1770.4 +/- 483.2 W) and 90% of 1RM (NSS-90 = 1493.1 +/- 296.2 W, SS-90 = 1723.8
      +/- 449.5 W). The current investigation has demonstrated significantly different
      kinetic and kinematic characteristics between squats without (NSS) and with an
      SS, which could ultimately aid in enhancing squat performance.

PMID- 22996019
TI  - Performance changes in National Collegiate Athletic Association Division I women
      basketball players during a competitive season: starters vs. nonstarters.
AB  - The effects of playing time on performance changes were examined in National
      Collegiate Athletic Association Division I women basketball players. Twelve
      basketball players (age = 20.6 +/- 1.5 years; height = 178.0 +/- 8.2 cm; weight =
      74.1 +/- 8.1 kg) were assessed before (PRE) and at the end of the regular
      basketball season (POST). Assessments included squat power; vertical jump (VJ)
      power; 20-second lower-body reaction test; 3 line drills; and subjective measures
      of energy, focus, fatigue, and alertness. Pre- to postseason comparisons were
      made between starters (28.3 +/- 5.2 minutes per game) and nonstarters (NSs) (8.3
      +/- 5.3 minutes per game). Data were analyzed for clinical significance using an
      approach based on the magnitude of change. Results revealed that starters were
      likely to have greater increases in absolute VJ peak power and relative VJ peak
      power (87.9 and 90.7%, respectively) and they were likely (81.6%) to have a
      greater average squat power than NSs. Subjective measures of energy, focus, and
      alertness were possibly (72.9%), very likely (97.3%), and likely (79.2%) to be
      lower in starters compared with NSs, respectively. Other performance measures
      showed unclear differences between starters and NSs. Pearson's product-moment
      correlation analysis revealed significant (p < 0.05) inverse correlations between
      playing time and Delta focus (r = -0.79) among all players. In conclusion,
      significant improvements in VJ performance and average squat power were seen in
      starters compared with NSs, despite greater decreases in energy, focus, and
      alertness. In this study, the monitoring of sport-specific performance changes
      pre and post season showed that performance measures can be maintained throughout
      an National Collegiate Athletic Association Division I women basketball season.

PMID- 22996020
TI  - Maximal power output and perceptual fatigue responses during a Division I female
      collegiate soccer season.
AB  - The purpose of this study was to investigate how maximal power output (PMAX), as
      measured via the inertial load cycling technique, changes throughout a collegiate
      soccer season in relation to training load completed. The current investigation
      took place throughout the 2010 Big XII soccer season. Nineteen Division I female
      collegiate soccer players (age: 19.9 +/- 1.2 years, stature: 165.1 +/- 6.6 cm,
      mass: 61.0 +/- 6.8 kg) from the same team completed regular inertial load cycling
      tests and perceptual fatigue questionnaires throughout the season. Players were
      divided into STARTERS and NON-STARTERS based on percentage of matches started
      throughout the season. The results demonstrated that STARTERS experience much
      greater load throughout the season than NON-STARTERS (2247 +/- 176 arbitrary
      units [AU] and 1585 +/- 174 AU, p < 0.05), accounted for by increased load during
      matches. This increased load throughout the season was accompanied by decline in
      PMAX in STARTERS (to 92.3 +/- 6.6%, p < 0.05), whereas PMAX was maintained in NON
      STARTERS for the duration of the season (99.0 +/- 4.9%). Furthermore, STARTERS
      experienced greater muscle soreness throughout the in-season period compared with
      NON-STARTERS. The main finding of this study is that PMAX declined throughout the
      middle and latter parts of the season in STARTERS, after experiencing
      significantly greater match loads than NON-STARTERS throughout the season. The
      current findings, combined with previous investigations, suggest that load needs
      to be carefully monitored throughout the in-season period to maintain optimal
      neuromuscular performance throughout a team's entire sporting season.

PMID- 22996021
TI  - Higher frequency of the ACTN3 R allele + ACE DD genotype in Japanese elite
      wrestlers.
AB  - In this study, the authors investigated the association between the ACTN3 and
      angiotensin-converting enzyme (ACE) genotypes and the performance of 135 Japanese
      elite male wrestlers. Fifty-two wrestlers had participated in world
      championships, including the Olympic Games, or had placed first in Japanese
      national championships and were classified as "international." The remaining 83
      wrestlers were classified as "national." The control group consisted of 333
      healthy Japanese college students majoring in physical education. In the ACTN3
      genotype distribution, a significant difference between the international and
      control groups was observed (p < 0.05). The ACE genotype distribution and allele
      frequency of all wrestlers significantly differed from those of the control
      subjects (p < 0.001). As compared with the control group, the odds ratio of the
      ACTN3 R allele + ACE DD genotype being international or national was 3.85 (95%
      confidence interval [CI], 2.10-7.03) or 1.37 (95% CI, 0.79-2.36), respectively.
      Our data suggest that the combination of ACTN3 and ACE gene polymorphisms is
      associated with the athletic status of Japanese elite wrestlers.

PMID- 22996022
TI  - Evaluation of the running-based anaerobic sprint test as a measure of repeated
      sprint ability in collegiate-level soccer players.
AB  - Repeated sprint ability (RSA) refers to an individual's ability to perform
      maximal sprints of short duration in succession with little recovery between
      sprints. The running-based anaerobic sprint test (RAST) has been adapted from the
      Wingate anaerobic test (WAnT) protocol as a tool to assess RSA and anaerobic
      power. The purpose of this study was to evaluate the relationship between
      performance variables and physiological responses obtained during the RAST and
      the WAnT using 8 collegiate-level soccer players. Participants performed a single
      trial of both the WAnT and the RAST. Breath-by-breath gas exchange was monitored
      throughout each trial, and blood lactate (BL) measures were recorded
      postexercise. The oxygen uptake (VO2) profile suggested that the RAST required
      greater contributions from aerobic metabolism although there was no difference in
      VO2peak (p < 0.05). Peak BL values were also similar between the RAST and the
      WAnT (p < 0.05). Neither peak physiological values nor performance variables
      (peak and mean power) were significantly correlated between protocols. The weak
      association in physiological responses indicates that different combinations of
      metabolic contributions exist between protocols, suggesting that individual
      performances on each test are not related in collegiate soccer players. Further
      studies on these relationships with players of other competitive levels and team
      sport athletes are warranted.

PMID- 22996023
TI  - Prevalence of metabolic syndrome risk factors in high school and NCAA division I
      football players.
AB  - Metabolic syndrome (MetSyn) is a clustering of metabolic and cardiovascular
      disease risk factors. The purpose of this study was to determine the prevalence
      of MetSyn risk factors in high school (HS) and college (College) football players
      and to examine if the prevalence varied according to body fat percent (%Fat). One
      hundred twenty-three males (height 179.0 +/- 6.7 cm; weight 89.4 +/- 19.6 kg)
      from 7 different high schools and 82 males (height 186.2 +/- 6.8 cm; weight 99.6
      +/- 16.8 kg) from one university participated. All testing occurred in the early
      morning after an overnight fast. %Fat, waist circumference, resting systolic and
      diastolic blood pressure, fasting triglyceride, high-density lipoprotein (HDL)
      cholesterol, and blood glucose were determined using standard testing procedures.
      The MetSyn risk factor levels were determined using American Heart Association
      criteria. Subjects were grouped by position and playing level (HS, College).
      Independent t-tests, chi-square analysis, 2-way analysis of variance, and path
      analytic models were used in the statistical analysis. Significance was set at p
      < 0.05. 6.8% (n = 14) of the sample met the American Heart Association criteria
      for MetSyn. Offensive and defensive linemen accounted for 92.3% of the players
      meeting MetSyn criteria with each playing level (HS, College) having 7 subjects.
      The MetSyn criteria differed significantly across %Fat. Obese players were more
      likely to meet the criteria for MetSyn. %Fat was a statistically significant
      predictor of mean arterial blood pressure, HDL cholesterol, and waist
      circumference. The MetSyn exists in both HS- and College-level football players,
      with almost all cases occurring in the athletes with the highest levels of %Fat
      (offensive/defensive lineman). Strength and conditioning coaches should be aware
      of the prevalence of MetSyn risk factors in offensive and defensive linemen and
      take appropriate actions to ensure athlete safety.

PMID- 22996025
TI  - Seasonal variations in VO2max, O2-cost, O2-deficit, and performance in elite
      cross-country skiers.
AB  - Long-term effects of training are important information for athletes, coaches,
      and scientists when associating changes in physiological indices with changes in
      performance. Therefore, this study monitored changes in aerobic and anaerobic
      capacities and performance in a group of elite cross-country skiers during a full
      sport season. Thirteen men (age, 23 +/- 2 years; height, 182 +/- 6 cm; body mass,
      76 +/- 8 kg; V2 roller ski skating VO2max, 79.3 +/- 4.4 ml.kg.min or 6.0 +/- 0.5
      L.min) were tested during the early, middle, and late preparation phase: June
      (T1), August (T2), and October (T3); during the competition phase:
      January/February (T4); and after early precompetition phase: June (T5). O2-cost
      during submaximal efforts, V[Combining Dot Above]O2peak, accumulated oxygen
      deficit (SigmaO2-deficit), and performance during a 1,000-m test were determined
      in the V2 ski skating technique on a roller ski treadmill. Subjects performed
      their training on an individual basis, and detailed training logs were
      categorized into different intensity zones and exercise modes. Total training
      volume was highest during the summer months (early preseason) and decreased
      toward and through the winter season, whereas the volume of high-intensity
      training increased (all p < 0.05). There was a significant main effect among
      testing sessions for 1,000 m time, O2-cost, and SigmaO2-deficit (Cohen's d effect
      size; ES = 0.63-1.37, moderate to large, all p < 0.05). In general, the changes
      occurred between T1 and T3 with minor changes in the competitive season (T3 to
      T4). No significant changes were found in V[Combining Dot Above]O2peak across the
      year (ES = 0.17, trivial). In conclusion, the training performed by elite cross
      country skiers induced no significant changes in V[Combining Dot Above]O2peak but
      improved performance, O2-cost, and SigmaO2-deficit.

PMID- 22996024
TI  - Frequency of combined resistance and aerobic training in older women.
AB  - The aim of this study was to determine the optimal frequency of combined aerobic
      and resistance training for improving muscular strength (MS), cardiovascular
      fitness (CF), and functional tasks (FTs) in women older than 60 years. Sixty
      three women were randomly assigned to 1 of 3 exercise training groups. Group 1
      performed 1 resistance exercise training (RET) and 1 aerobic exercise training
      (AET) session per week (AET/RET 1 * wk); group 2 performed 2 RET and 2 AET
      sessions per week (AET/RET 2 * wk); and group 3 performed 3 RET and 3 AET
      sessions per week (AET/RET 3 * wk). MS, CF, and FT measurements were made
      pretraining and 16 weeks posttraining. Repeated-measures analysis of variance
      indicated a significant time effect for changes in MS, CF, and FT, such that all
      improved after training. However, there were no significant training group or
      training group * time interactions. Sixteen weeks of combined AET/RET (1 * wk, 2
      * wk, or 3 * wk) lead to significant improvements in MS, CF, exercise economy,
      and FT. However, there were no significant differences for MS, CF, or FT outcomes
      between groups.

PMID- 22996026
TI  - Seasonal variation of leg stiffness in professional Australian rules footballers.
AB  - Leg stiffness (Kleg) is an important component to consider in both performance
      and injury in the Australian Football League (AFL). Kleg has not yet been
      examined longitudinally throughout an entire AFL season. A unilateral hop test
      was used to measure Kleg in the left and right legs of 25 professional AFL
      players (24.9 +/- 4.3 years, 86.8 +/- 8.1 kg, 187.0 +/- 7.3 cm). Kleg was
      assessed at least once per month for each participant. Furthermore, the session
      rate of perceived exertion method was used to quantify the average weekly
      training loads experienced by the participants. One-way analysis of variance
      revealed no significant difference between the average monthly bilateral Kleg
      scores; however, average weekly training loads varied between 1,400 and 2,000 AU,
      depending on the training period. Thirteen participants were randomly selected to
      perform hop tests on 2 consecutive weeks. Reliability tests revealed these
      measurements to have a typical error of the measurement of 4.15% and an
      intraclass correlation of 0.8, proving the methods to be reliable. Although
      training intensity appears to vary, Kleg does not fluctuate significantly across
      an entire AFL season, suggesting that weekly training loads between 1,400 and
      2,000 AU may be prescribed without the risk of fluctuating stiffness levels.

PMID- 22996027
TI  - The effects of uphill vs. level-grade high-intensity interval training on VO2max,
      Vmax, V(LT), and Tmax in well-trained distance runners.
AB  - Uphill running represents a frequently used and often prescribed training tactic
      in the development of competitive distance runners but remains largely
      uninvestigated and unsubstantiated as a training modality. The purpose of this
      investigation included documenting the effects of uphill interval training
      compared with level-grade interval training on maximal oxygen consumption
      (VO2max), the running speed associated with VO2max (Vmax), the running speed
      associated with lactate threshold (V(LT)), and the duration for which Vmax can be
      sustained (Tmax) in well-trained distance runners. Thirty-two well-trained
      distance runners (age, 27.4 +/- 3.8 years; body mass, 64.8 +/- 8.9 kg; height,
      173.6 +/- 6.4 cm; and VO2max, 60.9 +/- 8.5 ml.min(-1).kg(-1)) received assignment
      to an uphill interval training group (G(Hill) = 12), level-grade interval
      training group (G(Flat) = 12), or control group (G(Con) = 8). G(Hill) and G(Flat)
      completed 12 interval and 12 continuous running sessions over 6 weeks, whereas
      G(Con) maintained their normal training routine. Pre- and posttest measures of
      VO2max, Vmax, V(LT), and Tmax were used to assess performance. A 3 * 2 repeated
      measures analysis of variance was performed for each dependent variable and
      revealed a significant difference in Tmax in both G(Hill) and G(Flat) (p < 0.05).
      With regard to running performance, the results indicate that both uphill and
      level-grade interval training can induce significant improvements in a run-to
      exhaustion test in well-trained runners at the speed associated with VO2max but
      that traditional level-grade training produces greater gains.

PMID- 22996028
TI  - Effect of long-term oral contraceptive use on determinants of endurance
      performance.
AB  - We examined the effect of long-term oral contraceptive (OC) use on endurance
      performance in recreationally active women. Eight women using OC (OC group) and 8
      women who were nonusers (CON group) performed a test to determine the peak oxygen
      uptake for cycling (V[Combining Dot Above]O2peak) and to estimate the anaerobic
      threshold (AT). Subjects also completed a continuous submaximal cycling test
      across 3 work stages (two 6-minute work stages below AT, and 1 above AT performed
      to exhaustion). Pulmonary gas exchange, heart rate (HR), blood pressure (BP),
      blood lactate concentration ([La]), and ratings of perceived exertion were
      measured throughout, and cycling economy was calculated. Physical characteristics
      were comparable between the groups (p > 0.05). Peak oxygen uptake (CON group:
      2.59 +/- 0.50 L.min; OC group: 2.13 +/- 0.20 L.min) and oxygen uptake at the AT
      (CON group: 1.47 +/- 0.27 L.min; OC group: 1.18 +/- 0.15 L.min) were
      significantly different (p < 0.05) between the groups. Expired minute
      ventilation, HR, BP, [La], and cycling economy for all constant-load work stages
      were not significantly different (p > 0.05) between the groups. Furthermore, time
      to exhaustion for severe-intensity cycling was similar (p > 0.05) between the CON
      and OC groups. The results of the present study suggest that long-term OC use
      negatively affects peak V[Combining Dot Above]O2 and V[Combining Dot Above]O2 at
      the AT but does not alter endurance exercise performance.

PMID- 22996029
TI  - The usefulness and reliability of fitness testing protocols for ice hockey
      players: a literature review.
AB  - Ice hockey, like most sports, uses fitness testing to assess athletes. This study
      reviews the current commonly used fitness testing protocols for ice hockey
      players, discussing their predictive values and reliability. It also discusses a
      range of less commonly used measures and limitations in current testing
      protocols. The article concludes with a proposed testing program suitable for ice
      hockey players.

PMID- 22996030
TI  - Does on-water resisted rowing increase or maintain lower-body strength?
AB  - Over the past 30 years, endurance volumes have increased by >20% among the rowing
      elite; therefore, informed decisions about the value of weight training over
      other possible activities in periodized training plans for rowing need to be
      made. The purpose of this study was to quantify the changes in lower-body
      strength development after two 14-week phases of intensive resisted on-water
      rowing, either incorporating weight training or rowing alone. Ten elite women
      performed 2 resisted rowing ("towing ropes," e.g., 8 * 3 minutes) plus 6
      endurance (e.g., 16-28 km at 70-80% maximum heart rate) and 2 rate-regulated
      races (e.g., 8,000 m at 24 strokes per minute) on-water each week. After a 4-week
      washout phase, the 14-week phase was repeated with the addition of 2 weight
      training sessions (e.g., 3-4 sets * 6-15 reps). Percent (+/-SD) and standardized
      differences in effects (effect size [ES] +/- 90% confidence limit) for 5
      repetition leg pressing and isometric pulling strength were calculated from data
      ratio scaled for body mass, log transformed and adjusted for pretest scores.
      Resisted rowing alone did not increase leg pressing (-1.0 +/- 5.3%, p = 0.51) or
      isometric pulling (5.3 +/- 13.4%, p = 0.28) strength. In contrast, after weight
      training, a moderately greater increase in leg pressing strength was observed (ES
      = 0.72 +/- 0.49, p = 0.03), although differences in isometric pulling strength
      were unclear (ES = 0.56 +/- 1.69, p = 0.52). In conclusion, intensive on-water
      training including resisted rowing maintained but did not increase lower-body
      strength. Elite rowers or coaches might consider the incorporation of high
      intensity nonfatiguing weight training concurrent to endurance exercise if
      increases in lower-body strength without changes in body mass are desired.

PMID- 22996031
TI  - Ultra-deep sequencing reveals hidden HIV-1 minority lineages and shifts of viral
      population between the main cellular reservoirs of the infection after therapy
      interruption.
AB  - Viral quasispecies population dynamics between monocytes and T-lymphocytes were
      analyzed in patients after highly active antiretroviral therapy (HAART)
      interruption, during a follow-up of 3-6 months. V3 env region underwent ultra
      deep pyrosequencing. Co-receptor usage prediction was performed by Position
      Specific Score Matrix Analysis. Phylogenetic trees were constructed to evaluate
      the relationships between the variants. Gene flow was also investigated. Even
      though at the moment of therapy interruption monocyte-derived HIV-1 genomes
      presented higher genetic heterogeneity than that of T-lymphocytes, at subsequent
      times, this difference in genetic heterogeneity disappeared, due to different
      waves of expansion and reduction of quasispecies variability associated with
      monocytes and T-lymphocytes. Phylogenetic analysis and gene flow evaluation
      supported the hypothesis of extensive interchange of variants between cellular
      compartments of the infection. A spread of proviral X4 lineages hidden in
      monocytes to T cells was observed, but this was not associated with an overall
      shift towards CXCR4 using variants during the observation period.

PMID- 22996032
TI  - Evaluation of cytotoxicity of different tobacco product preparations.
AB  - Acute exposure to cigarette smoke or its components triggers diverse cellular
      effects, including cytotoxicity. However, available data regarding the potential
      cytotoxic effects of smokeless tobacco (ST) extracts lack consensus. Here, we
      investigated the relative biological effects of 2S3 reference ST, and whether ST
      elicits differential cellular/molecular responses compared to combustible tobacco
      product preparations (TPPs) prepared from 3R4F cigarettes. Total particulate
      matter (TPM) and whole smoke conditioned medium (WS-CM) were employed as
      combustible TPPs, while the ST extract was used as non-combustible TPP. HL60,
      THP1 cells and human PBMCs were used to examine the effects of TPPs in short-term
      cell culture. Corresponding EC(50) values, normalized for nicotine content of the
      TPPs, suggest that combustible TPPs induced higher cytotoxicity as follows: WS-CM
      TPM >= ?ST extract>nicotine. While all three TPPs induced detectable levels of
      DNA damage and IL8 secretion, the combustible TPPs were significantly more potent
      than the ST preparation. The major PBMC subsets showed differential cytotoxicity
      to combustible TPPs as follows: CD4>CD8>monocytes>NK cells. These findings
      suggest that, relative cytotoxic and other cell biological effects of TPPs are
      dose-dependent, and that ST extract is the least cytotoxic TPP tested in this
      study.

PMID- 22996033
TI  - Preparation and characterization of grafted imprinted monolith for capillary
      electrochromatography.
AB  - In this paper, a molecularly imprinted polymer (MIP) coating grafted to a
      trimethylolpropane trimethacrylate (TRIM) core material for CEC was reported. The
      core monolith was prepared with a solution of 20% (w/w) TRIM in a mixture of
      porogen and a polymerization precursor, which can generate a stable
      electroosmotic flow due to the formation of ionizable groups after
      postpolymerization hydrolization. Graft polymerization took place on the
      resultant TRIM monolith with a mixture of template, methacrylic acid, and
      ethylene glycol dimethacrylate. Strong recognition ability (selectivity factor
      was 5.83) for S-amlodipine and resolution of enatiomers separation (up to 7.99)
      were obtained on the resulting grafted imprinted monolith in CEC mode. The
      influence of CEC conditions on chiral separation, including the composition of
      mobile phase, pH value, and the operating voltages was studied. These results
      suggest that the method of grafted polymerization reported here allows a rapid
      development of MIP monolith once core materials with desired properties are
      available, and is a good alternative to prepare CEC-based monolithic MIPs.

PMID- 22996034
TI  - Synthesis of a Candida albicans tetrasaccharide spanning the beta1,2-mannan
      phosphodiester alpha-mannan junction.
AB  - The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein
      with a glycan chain containing predominantly an alpha-linked mannose backbone
      with alpha-mannose branches. A minor beta-mannan component is attached to the
      branches either via a glycosidic bond (acid stable beta-mannan) or a
      phosphodiester bond (acid-labile beta-mannan). The alpha-mannan residues of the
      cell wall phosphomannan do not afford protective antibody, while the beta-mannan
      portion is a protective antigen and has become an attractive target as the key
      epitope of a conjugate vaccine. We report the first synthesis of a
      tetrasaccharide 1 consisting of a beta1,2-mannopyranosyl trisaccharide linked via
      a phosphodiester to methyl alpha-mannopyranoside. This encompasses the attachment
      site of the acid labile beta-mannan to the alpha-mannan component of the cell
      wall phosphomannan. The trisaccharide was formed by an iterative process to first
      create a beta-glucopyranoside linkage and then epimerize the C-2 center via an
      oxidation-reduction sequence. The phosphate diester linkage was accessed via an
      anomeric H-phosphonate. The binding of phosphomannan fragment 1 with the
      protective antibody C3.1 has been evaluated and compared with a beta
      mannotrioside in hapten inhibition experiments. The observed activities are
      rationalized with a model for docked in the binding site of C3.1.

PMID- 22996035
TI  - An efficient and robust analysis of covariance model for baseline adjustment in
      parallel-group thorough QT/QTc studies.
AB  - Baseline adjustment is an important consideration in thorough QT/QTc studies for
      non-antiarrhythmic drugs. The time-matched baseline is often used in practice to
      adjust for the within-subject diurnal effects. More recently, the day-averaged
      baseline has been proposed in the literature to improve the efficiency of
      treatment comparisons for the primary and assay sensitivity hypotheses. We
      recommend an analysis of covariance (ANCOVA) model with change from the time
      matched baseline as the response and both the time-matched baseline and the day
      averaged baseline as the covariates. This model adjusts for the within-subject
      diurnal effects and at the same time is more efficient and robust than the ANCOVA
      models based on either the time-matched baseline alone or the day-averaged
      baseline alone.

PMID- 22996036
TI  - Psychological responses of terminally ill patients who are experiencing
      suffering: A qualitative study.
AB  - BACKGROUND: Suffering is not only characterized by the feeling of being
      threatened, but also by the feeling of impotence to deal with such a threat.
      Literature identifies a terminal illness as a period during which several
      experiences implying an intense suffering are endured, but little attention has
      been paid to the psychological responses when reacting to threats. OBJECTIVE:
      Identify the psychological responses that terminally ill patients put in place to
      face up to the demands of the end of life, as a foundation for future nursing
      interventions. DESIGN: Qualitative methodology with an interpretative
      phenomenological approach. SETTINGS: Different hospitals health centers around
      the region of Granada (Spain). PARTICIPANTS: Twenty-four participants were
      finally chosen to take part in the research. The sampling procedure was
      intentional, and it was made taking into account exclusion and inclusion
      criteria. Patients with a cognitive impairment, who had been diagnosed with
      psychiatric alterations, who at that time suffered from uncontrollable symptoms
      such as intense pain were excluded from the sample. METHODS: The patients were
      interviewed following a script (semistructured interview) carried out using the
      suggested theoretical framework. The interviews were analyzed using the sequence
      suggested by Strauss and Corbin: Open, axial and selective codification. RESULTS:
      The analysis of the participants' answers to the different questions of the semi
      structured interview has allowed us to identify a main category "To realize that
      life is short". There are three categories where the different ways of facing up
      to the end of life concentrate: "Re-Evaluation of life", "Opportunity for
      growth", "Resignation/Acceptance". CONCLUSIONS: Nurses, have to try to alleviate
      the impact the terminal illness has on the subject, not only by controlling the
      symptoms but also encouraging the patients responses, by promoting the feeling of
      satisfaction in life, providing honest and sensitive information, establishing
      with the patient realistic goals, and facilitating a quality communication
      between patients and their family.

PMID- 22996037
TI  - The challenges of working in underserved areas: a qualitative exploratory study
      of views of policy makers and professionals.
AB  - BACKGROUND: The inadequate number of health care providers, particularly nurses,
      in underserved areas is one of the biggest challenges for health policymakers.
      There is a scarcity of research in Jordan about factors that affect nurse
      staffing and retention in underserved areas. PURPOSE: To elucidate the views of
      staff nurses working in underserved areas, directors of health facilities in
      underserved areas and key informants from the policy and education arena on
      issues of staffing and retention of nurses in underserved areas. METHODS: An
      exploratory study using a qualitative approach with semi-structured interviews
      was utilized to elucidate the views of 22 key informants from the policy and
      education arena, 11 directors of health centers, and 19 staff nurses on issues
      that contribute to low staffing and retention of nurses in underserved areas. The
      five stage 'framework approach' proposed by Bryman et al. (1993) was utilized for
      data analysis. RESULTS: Nursing shortage in underserved areas in Jordan are
      exacerbated by a lack of financial incentives, poor transportation and remoteness
      of these areas, bad working conditions, and lack of health education institutions
      in these areas, as well as by opportunities for internal and external migration.
      Young Jordanian male nurses usually grab any opportunity to migrate and work
      outside the country to improve their financial conditions; whereas, female nurses
      are more restricted and not encouraged to travel abroad to work. Several
      strategies are suggested to enhance retention in these areas, such as promoting
      financial incentives for staff to work there, enhancing the transportation
      system, and promoting continuous and academic education. CONCLUSION: Nurses'
      administrators and health care policy makers could utilize the findings of the
      present study to design and implement comprehensive interventions to enhance
      retention of staff in underserved areas.

PMID- 22996038
TI  - Real-life comparison of DPP4-inhibitors with conventional oral antidiabetics as
      add-on therapy to metformin in elderly patients with type 2 diabetes: the
      HYPOCRAS study.
AB  - AIM: Despite half of all type 2 diabetes mellitus (T2DM) patients being over 65
      and treatment being complicated by an elevated risk of iatrogenic hypoglycaemia,
      information about antidiabetic treatment is scarce in this age group. This
      prospective observational study compares DPP4-inhibitors (DPP4-i) with
      conventional oral antidiabetic drugs (COAD) in the real-life treatment of elderly
      patients with T2DM uncontrolled on metformin alone. METHODS: Two treatment
      cohorts (DPP4-i and COAD, constituted on the basis of the GP decision of add-on
      therapy at the 1st visit) were compared after 6months. The primary objective was
      to assess the incidence of hypoglycaemic episodes in relationship with glycaemic
      control assessed by HbA(1c) level. RESULTS: Demographics and disease history were
      comparable between the two cohorts (DPP4-i, n=931 and COAD, n=257) at baseline.
      The incidence of hypoglycaemia/severe hypoglycaemia was significantly higher over
      6months in the COAD cohort (20.1%/2.4% vs. 6.4%/0.1%; P<0.001) whereas similar
      improvements were observed in glycaemic control with HbA(1c) down from 7.9% to
      7.0% (COAD) and 6.9% (DPP4-i). The 7% target was reached without hypoglycaemia in
      more patients in the DPP4-i than in COAD cohort (59.7% vs. 45.5%; P<0.001).
      Patients in both cohorts who experienced hypoglycaemia more frequently had a pre
      existing diabetic complication. The COAD was more likely to be discontinued (6.6%
      vs. 1.6%; P<0.001). CONCLUSION: This large cohort study of elderly T2DM patients
      in France shows that the incidence of hypoglycaemia was three times higher in
      patients prescribed a COAD versus a DPP4-i after 6months while both treatments
      induced satisfactory glycaemic control.

PMID- 22996040
TI  - Intramolecular vibrational coupling in water molecules revealed by compatible
      multiple nonlinear vibrational spectroscopic measurements.
AB  - The complex structure of water and its interactions with solid surfaces require
      the development of multiple vibrational spectroscopic measurements to study the
      molecular structure of interfacial water and bulk water near the solid surface.
      In this study, a newly developed compatible multiple nonlinear vibrational
      spectroscopy system has been applied to investigate the molecular structure of
      water in the interfacial region of an ionic solid (CaF(2) substrate) and bulk
      isotopic D(2)O-HOD-H(2)O mixtures. Using this compatible system, the sum
      frequency generation (SFG) vibrational spectra and infrared-infrared-visible
      three-pump-field four-wave-mixing (IIV-TPF-FWM) spectra of the same water
      molecules can be collected at the same experimental geometry. It is found that
      SFG and IIV-TPF-FWM can be used to characterize the molecular structures of
      interfacial water and bulk water molecules at an interfacial distance below 42
      nm, respectively. SFG and IIV-TPF-FWM results both suggest an intramolecular
      vibrational coupling dominates the spectra. The results achieved by this method
      are helpful to clarify the origination of the vibrational coupling of the
      interfacial water as well as the bulk water near the solid surface.

PMID- 22996039
TI  - Comparison of MCNPX and Geant4 proton energy deposition predictions for clinical
      use.
AB  - Several different Monte Carlo codes are currently being used at proton therapy
      centers to improve upon dose predictions over standard methods using analytical
      or semi-empirical dose algorithms. There is a need to better ascertain the
      differences between proton dose predictions from different available Monte Carlo
      codes. In this investigation Geant4 and MCNPX, the two most-utilized Monte Carlo
      codes for proton therapy applications, were used to predict energy deposition
      distributions in a variety of geometries, comprising simple water phantoms, water
      phantoms with complex inserts and in a voxelized geometry based on clinical CT
      data. The Gamma analysis was used to evaluate the differences of the predictions
      between the codes. The results show that in all the cases the agreement was
      better than clinical acceptance criteria.

PMID- 22996041
TI  - How Atg18 and the WIPIs sense phosphatidylinositol 3-phosphate.
AB  - The key autophagic lipid sensors are Atg18 in yeast and the WIPI proteins in
      mammals. Atg18 and the WIPIs belong to the PROPPIN family of proteins. PROPPINs
      are seven- bladed beta-propellers that bind to phosphatidylinositol 3-phosphate
      (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. In order to
      understand how PROPPINs bind phosphoinositides, we have determined the crystal
      structure of a representative, biochemically tractable PROPPIN, Hsv2 of
      Kluveromyces lactis. The structure revealed that PROPPINs contain two
      phosphoinositide binding sites which cooperate with a hydrophobic anchoring loop
      in membrane binding. These three binding elements cooperate in function, as
      demonstrated by the incremental loss of function in Atg18 mutants impaired in
      combinations of the two phosphoinositide binding sites and the hydrophobic loop.

PMID- 22996042
TI  - Autophagic flux, supported by toll-like receptor 2 activity, defends against the
      carcinogenesis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), the most common primary malignant liver tumor, is
      the third leading cause of cancer deaths. The pathogenesis of HCC is closely
      associated with chronic liver inflammation fired by a variety of stimulates such
      as virus infection and metabolic stress. Recent work indicates that autophagy, a
      homeostatic self-degradation process, which decides cell survival or death upon
      stress, acts as an effector machinery of immune systems in defending microbial
      invasion and carcinogenesis. SQSTM1 is a selective target and receptor of
      autophagy, and the protein content of SQSTM1 reflects the level of autophagic
      flux in cells. Through degrading SQSTM1, decreasing SQSTM1 aggregates, and
      therefore interrupting the positive feedback between SQSTM1 aggregates and ROS
      production, autophagy plays a protective role against hepatocellular carcinoma.
      Indeed, our studies indicate that toll-like receptor 2 (TLR2)-mediated immune
      activities in the genotoxic carcinogen diethylnitrosamine (DEN)-injured liver
      tissue provide essential nutrient stimulates to induce intracellular senescence,
      which can ensure the activation and maturation of autophagy in liver cells. Loss
      of TLR2-mediated immune activity and senescence leads to the attenuation of
      autophagic flux, which cannot eliminate SQSTM1 aggregates, ROS accumulation, and
      DNA damage, and facilitates the development and progression of HCC.

PMID- 22996043
TI  - A chirality rewriting cycle mediated by a dynamic cyclen-calcium complex.
AB  - A Ca(2+) complex with octadentate cyclen having three pyridines and one triazole
      on its sidearms mediated two-point chirality transfer from an external chiral
      source to the coordinating pyridine and coumarin moieties. The induced chirality
      information was repeatedly written, deleted, and rewritten by coupling with
      esterification of the coordinating external chiral anion.

PMID- 22996044
TI  - Personality assessment and its association with genetic factors in captive Asian
      and African elephants.
AB  - Elephants live in a complex society based on matrilineal groups. Management of
      captive elephants is difficult, partly because each elephant has a unique
      personality. For a better understanding of elephant well being in captivity, it
      would be helpful to systematically evaluate elephants' personalities and their
      underlying biological basis. We sent elephant' personality questionnaires to
      keepers of 75 elephants. We also used 196 elephant DNA samples to search for
      genetic polymorphisms in genes expressed in the brain that have been suggested to
      be related to personality traits. Three genes, androgen receptor (AR), fragile X
      related mental retardation protein interacting protein (NUFIP2), and acheate
      scute homologs 1 (ASH1) contained polymorphic regions. We examined the
      association of personality with intraspecific genetic variation in 17 Asian and
      28 African elephants. The results suggest that the ASH1 genotype was associated
      with neuroticism in Asian elephants. Subjects with short alleles had lower scores
      of neuroticism than those with long alleles. This is the first report of an
      association between a genetic polymorphism and personality in elephants.

PMID- 22996045
TI  - Differential neural network of checking versus washing symptoms in obsessive
      compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this
      study was to investigate differential neural responses to a symptom provocation
      task in drug-free patients who have predominantly aggression/checking symptoms
      (Checkers) and patients with contamination/washing symptoms (Washers). We
      compared the Checkers (n=10) and the Washers (n=12) separately to normal controls
      during the symptom provocation tasks using fMRI (functional magnetic resonance
      imaging). Moreover, we performed correlative analysis in each OCD group between
      brain activation and symptom severity. The Checkers showed hypoactivation in the
      left caudate and left anterior cingulate cortex (ACC) compared to the normal
      controls and a positive correlation between activated brain areas and symptom
      severity in the left ACC. The Washers showed hyperactivation in several bilateral
      cortico-cerebellar regions and a positive correlation between symptom severity
      and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are
      associated with checking rituals and that large cortical brain regions are
      related to washing rituals.

PMID- 22996047
TI  - Beat phenomena in metal nanowires, and their implications for resonance-based
      elastic property measurements.
AB  - The elastic properties of 1D nanostructures such as nanowires are often measured
      experimentally through actuation of nanowires at their resonance frequency, and
      then relating the resonance frequency to the elastic stiffness using the
      elementary beam theory. In the present work, we utilize large scale molecular
      dynamics simulations to report a novel beat phenomenon in [110] oriented Ag
      nanowires. The beat phenomenon is found to arise from the asymmetry of the
      lattice spacing in the orthogonal elementary directions of [110] nanowires, i.e.
      the [110] and [001] directions, which results in two different principal moments
      of inertia. Because of this, actuations imposed along any other direction are
      found to decompose into two orthogonal vibrational components based on the
      actuation angle relative to these two elementary directions, with this phenomenon
      being generalizable to <110> FCC nanowires of different materials (Cu, Au, Ni, Pd
      and Pt). The beat phenomenon is explained using a discrete moment of inertia
      model based on the hard sphere assumption; the model is utilized to show that
      surface effects enhance the beat phenomenon, while effects are reduced with
      increasing nanowire cross-sectional size or aspect ratio. Most importantly, due
      to the existence of the beat phenomena, we demonstrate that in resonance
      experiments only a single frequency component is expected to be observed,
      particularly when the damping ratio is relatively large or very small.
      Furthermore, for a large range of actuation angles, the lower frequency is more
      likely to be detected than the higher one, which implies that experimental
      predictions of the Young's modulus obtained from resonance may in fact be under
      predictions. The present study therefore has significant implications for
      experimental interpretations of the Young's modulus as obtained via resonance
      testing.

PMID- 22996046
TI  - Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the
      antidepressant-like effect caused by hesperidin in mice.
AB  - The present study investigated a possible antidepressant-like activity of
      hesperidin using two predictive tests for antidepressant effect in mice: the
      forced swimming test (FST) and the tail suspension test (TST). Results
      demonstrated that hesperidin (0.1, 0.3 and 1 mg/kg, intraperitoneal, i.p.)
      decreased the immobility time in the FST and TST without affecting the locomotor
      activity in the open field test. The antidepressant-like effect of hesperidin
      (0.3 mg/kg) on the TST was prevented by the pretreatment of mice with p
      chlorophenylalanine methyl ester (pCPA; 100 mg/kg, i.p., an inhibitor of
      serotonin synthesis) and WAY100635 (0.1 mg/kg, subcutaneous, s.c., a selective 5
      HT(1A) receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p.,
      an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)
      adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a beta-adrenoceptor
      antagonist), AMPT (100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase),
      SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist), sulpiride (50
      mg/kg, i.p., a dopamine D(2) receptor antagonist), ketanserin (1mg/kg, i.p., a 5
      HT(2A/2C) receptor antagonist) or MDL72222 (1 mg/kg, i.p., a 5-HT(3) receptor
      antagonist) did not block the antidepressant-like effect of hesperidin (0.3
      mg/kg, i.p.) in the TST. Administration of hesperidin (0.01 mg/kg, i.p.) and
      fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like
      effect in the TST. The antidepressant-like effect caused by hesperidin in mice in
      the TST was dependent on an interaction with the serotonergic 5-HT(1A) receptors.
      Taken together, these results suggest that hesperidin possesses antidepressant
      like property and may be of interest source for therapeutic agent for the
      treatment of depressive disorders.

PMID- 22996048
TI  - The diagnostic accuracy and strength of agreement between endoscopic ultrasound
      and histopathology in the staging of ampullary tumors.
AB  - AIM: Ampullary tumors are rare. Reports on ampullary tumor staging are
      heterogeneous and combine both periampullary and ampullary tumors. This study
      assessed the performance of endoscopic ultrasound (EUS) in the local staging of
      ampullary tumors only. METHODS: Data were collected retrospectively. We included
      patients with an ampullary tumor who underwent EUS and surgical resection. Tumor
      (T) and nodal (N) TNM staging for EUS and histopathological (HP) staging were
      compared. RESULTS: From 2009 to 2010, a total of 79 patients with ampullary
      tumors were identified. Of these, 26 had both EUS and Whipple's surgery and were
      included (28 did not undergo resection, 13 had palliative surgery only and 12 had
      resection without EUS). For T staging by HP, there were 2 (7.7 %) T1, 11 (42.3 %)
      T2, 12 (46.2 %) T3 and 1 (3.8 %) T4 tumors. The accuracy of EUS T staging was
      73.1 % with a Kappa value of 0.564 (p < 0.0001). The sensitivity, specificity,
      positive predictive value (PPV), negative predictive values (NPV) of EUS,
      respectively were 50.0 %, 91.7 %, 33.3 % and 95.7 % for T1 tumors; 81.8 %, 80.0
      %, 75.0 % and 85.7 % for T2; 75.0 %, 92.9 %, 90.0 % and 81.3 % for T3 tumors. For
      N staging by HP, 17 (65.4 %) were N0 and 9 (34.6 %) N1. The N staging diagnostic
      accuracy was 80.8 % with a Kappa value of 0.586 (p = 0.003). The sensitivity,
      specificity, PPV, NPV for N0 disease were 82.4 %, 77.8 %, 87.5 % and 70.0 %,
      respectively while for N1 they were 77.8 %, 82.4 %, 70.0 % and 87.5 %,
      respectively. CONCLUSIONS: EUS had a moderate strength of agreement with
      histopathology for both T and N staging, and a high diagnostic accuracy for nodal
      staging.

PMID- 22996049
TI  - Quantitative optical coherence tomography of fluid-filled oral mucosal lesions.
AB  - The decision of selecting the most representative site for the biopsy of fluid
      filled lesions can be difficult. This may be attributed to the poor delineation
      of the correct lesional site by clinical observation alone. In this study,
      optical coherence tomography is used to quantify the contrast between solid- and
      fluid-filled lesions by measuring the light intensity change at the tissue-fluid
      interface (intensity drop). This parameter was measured from sequential axial
      scans (n ~ 10(6) per sample) of 3D optical coherence tomography (OCT) datasets
      from control tissues (n = 14) and fluid-filled lesions (n = 7) and displayed as a
      2D-scaled intensity drop (SID) image. The results of the SID image allowed for
      discrimination, characterisation and extent of a fluid filled region. The
      differentiation of normal and fluid-filled areas using individual SID values
      yielded both a sensitivity and specificity of approximately 80 %. OCT
      complemented by SID analysis provides a potential in vivo clinical tool that
      would enable non-invasive objective visualisation of the oral mucosa. 

PMID- 22996050
TI  - Naturalistic arm movements during obstacle avoidance in 3D and the identification
      of movement primitives.
AB  - By studying human movement in the laboratory, a number of regularities and
      invariants such as planarity and the principle of isochrony have been discovered.
      The theoretical idea has gained traction that movement may be generated from a
      limited set of movement primitives that would encode these invariants. In this
      study, we ask if invariants and movement primitives capture naturalistic human
      movement. Participants moved objects to target locations while avoiding obstacles
      using unconstrained arm movements in three dimensions. Two experiments
      manipulated the spatial layout of targets, obstacles, and the locations in the
      transport movement where an obstacle was encountered. We found that all movement
      trajectories were planar, with the inclination of the movement plane reflecting
      the obstacle constraint. The timing of the movement was consistent with both
      global isochrony (same movement time for variable path lengths) and local
      isochrony (same movement time for two components of the obstacle avoidance
      movement). The identified movement primitives of transport (movement from start
      to target position) and lift (movement perpendicular to transport within the
      movement plane) varied independently with obstacle conditions. Their scaling
      accounted for the observed double peak structure of movement speed. Overall, the
      observed naturalistic movement was astoundingly regular. Its decomposition into
      primitives suggests simple mechanisms for movement generation.

PMID- 22996051
TI  - Improving quantification of intravascular fluorescence imaging using structural
      information.
AB  - Intravascular near-infrared fluorescence (iNIRF) imaging can enable the in vivo
      visualization of biomarkers of vascular pathology, including high-risk plaques.
      The technique resolves the bio-distribution of systemically administered
      fluorescent probes with molecular specificity in the vessel wall. However, the
      geometrical variations that may occur in the distance between fibre-tip and
      vessel wall can lead to signal intensity variations and challenge quantification.
      Herein we examined whether the use of anatomical information of the cross-section
      vessel morphology, obtained from co-registered intravascular ultrasound (IVUS),
      can lead to quantification improvements when fibre-tip and vessel wall distance
      variations are present. The algorithm developed employs a photon propagation
      model derived from phantom experiments that is used to calculate the relative
      attenuation of fluorescence signals as they are collected over 360 degrees  along
      the vessel wall, and utilizes it to restore accurate fluorescence readings. The
      findings herein point to quantification improvements when employing hybrid iNIRF,
      with possible implications to the clinical detection of high-risk plaques or
      blood vessel theranostics.

PMID- 22996052
TI  - Synthesis of deoxynucleoside triphosphates that include proline, urea, or
      sulfonamide groups and their polymerase incorporation into DNA.
AB  - To expand the chemical array available for DNA sequences in the context of in
      vitro selection, I present herein the synthesis of five nucleoside triphosphate
      analogues containing side chains capable of organocatalysis. The synthesis
      involved the coupling of L-proline-containing residues (dU(tP)TP and dU(cP)TP), a
      dipeptide (dU(FP)TP), a urea derivative (dU(Bpu)TP), and a sulfamide residue
      (dU(Bs)TP) to a suitably protected common intermediate, followed by
      triphosphorylation. These modified dNTPs were shown to be excellent substrates
      for the Vent (exo(-)) and Pwo DNA polymerases, as well as the Klenow fragment of
      E. coli DNA polymerase I, although they were only acceptable substrates for the 9
      degrees N(m) polymerase. All of the modified dNTPs, with the exception of
      dU(Bpu)TP, were readily incorporated into DNA by the polymerase chain reaction
      (PCR). Modified oligonucleotides efficiently served as templates for PCR for the
      regeneration of unmodified DNA. Thermal denaturation experiments showed that
      these modifications are tolerated in the major groove. Overall, these heavily
      modified dNTPs are excellent candidates for SELEX.

PMID- 22996053
TI  - Biochemical lung, liver and kidney markers and early death among elderly
      following hip fracture.
AB  - INTRODUCTION: In the elderly, hip fracture is a common injury associated with
      high early mortality dominated by cardiorespiratory and thromboembolic events.
      Identification of risk factors that can be modified by treatment has caught
      attention over the last years. This study was conducted to assess biological
      markers on perioperative organ dysfunction and its association with early
      mortality within 3 months after surgery. METHOD: Blood samples were collected
      before, during and until 4 days after surgery. Analyses on PaO(2), alanine
      aminotransaminase (ALAT), gamma-glutamyl transpeptidase (g-GT) and creatinine
      were performed and used as markers on lung, liver and kidney functions. PATIENTS:
      Three hundred and two patients over 75 years of age with acute dislocated hip
      fracture were consecutively enrolled from two hospitals in Norway. RESULTS: We
      found a positive correlation between the plasma levels of ALAT, creatinine and
      death, and an inverse relationship between PaO(2) and death. After controlling
      for confounding factors such as sex, age and comorbidity, ALAT and creatinine
      levels were shown to be significantly and independently related to risk for fatal
      outcome. CONCLUSION: Our results provide data on clinically important biomarkers
      in patients undergoing hip fracture surgery. We suggest a stronger emphasis on
      monitoring and correcting these biomarkers when possible.

PMID- 22996054
TI  - Challenges of developing a pan-Asian curriculum:  lessons for global nuclear
      medicine training.

PMID- 22996055
TI  - Recent data regarding low versus high 131I activity for remnant ablation in
      differentiated thyroid cancer are not generalizable beyond eligibility criteria.

PMID- 22996057
TI  - Glycosylation effects on cancer development.

PMID- 22996058
TI  - Implicit sequence learning in dyslexia: a within-sequence comparison of first-
      and higher-order information.
AB  - The present study examines implicit sequence learning in adult dyslexics with a
      focus on comparing sequence transitions with different statistical complexities.
      Learning of a 12-item deterministic sequence was assessed in 12 dyslexic and 12
      non-dyslexic university students. Both groups showed equivalent standard reaction
      time increments when the sequence was unexpectedly changed, suggesting that
      learning of the sequence took place. However, a novel analysis comparing
      transitions of differing complexity within the learning blocks indicated that
      dyslexic participants were impaired only for higher-order but not first-order
      sequence learning. No difference was found in the explicit awareness contribution
      between the two groups and this was found not to correlate with reaction time
      performance. This result suggests that statistical complexity of the sequence may
      account for intact and impaired learning performance in dyslexia.

PMID- 22996059
TI  - One-step hydrothermal synthesis of carboxyl-functionalized upconversion phosphors
      for bioapplications.
AB  - In this paper, we report a facile one-step hydrothermal method to synthesize
      phase-, size-, and shape-controlled carboxyl-functionalized rare-earth
      fluorescence upconversion phosphors by using a small-molecule binary acid, such
      as malonic acid, oxalic acid, succinic acid, or tartaric acid as capping agent.
      The crystals, from nano- to microstructures with diverse shapes that include
      nanospheres, microrods, hexagonal prisms, microtubes, microdisks, polygonal
      columns, and hexagonal tablets, can be obtained with different reaction times,
      reaction temperatures, molar ratios of capping agent to sodium hydroxide, and by
      varying the binary acids. Fourier transform infrared, thermogravimetric analysis,
      and upconversion luminescence spectra measurements indicate that the synthesized
      NaYF(4):Yb/Er products with hydrophilic carboxyl-functionalized surface offer
      efficient upconversion luminescent performance. Furthermore, the
      antibody/secondary antibody conjugation can be realized by the carboxyl
      functionalized surfaces of the upconversion phosphors, thus indicating the
      potential bioapplications of these kinds of materials.

PMID- 22996060
TI  - Use of the MC-FAQ and MMSE-FAQ in cognitive screening of older African Americans,
      Hispanic Americans, and European Americans.
AB  - OBJECTIVE: The purpose of this study was to examine the performance of the Mini
      Cog-Functional Activities Questionnaire (MC-FAQ) and the Mini-Mental State
      Examination-Functional Activities Questionnaire (MMSE-FAQ) in cognitive screening
      of a multiethnic sample of older adults. DESIGN: This is a descriptive
      psychometric study. SETTING: Cognitive screening was done in senior centers, at
      health fairs, and within the nine participating memory disorder centers in the
      State of Florida. PARTICIPANTS: African American, Hispanic American, and European
      American older adults who participated in this screening were matched on gender,
      age within 3 years and education within 3 years yielding a sample of 225.
      MEASUREMENTS: The MC-FAQ is a combination of the Mini-Cog and Functional
      Activities Questionnaire. The MMSE-FAQ combines the MMSE with the FAQ. The
      Geriatric Depression Scale was used to assess depressive symptoms. RESULTS:
      African Americans reported significantly less depressive symptoms (F[2, 217] =
      10.31, p <0.001) and European Americans had significantly higher mean MMSE scores
      than the other two groups (F[2, 222] = 3.33, p = 0.037). Participants did not
      differ by ethnic group on the MC-FAQ or MMSE-FAQ classifications of normal, mild
      cognitive impairment, or dementia. Age, years of education, and depressive
      symptoms were significant predictors of MC-FAQ and MMSE-FAQ classifications.
      CONCLUSIONS: The results suggest that these combinations of screening measures
      may have less culture bias than the MMSE alone. Sensitivity and specificity
      should be evaluated in these groups with confirmatory neurological and
      psychiatric diagnosis.

PMID- 22996068
TI  - Erratum to: Perceptions of genetic research in three rural Appalachian Ohio
      communities.

PMID- 22996069
TI  - In vitro platelet antiaggregatory properties of 4-methylcoumarins.
AB  - Platelets play a crucial role in physiological haemostasis. However, in coronary
      arteries damaged by atherosclerosis, enhanced platelet aggregation, with
      subsequent thrombus formation, is a precipitating factor in acute myocardial
      infarction. Current therapeutic approaches are able to reduce approximately one
      quarter of cardiovascular events, but they are associated with an increased risk
      of bleeding and in some resistant patients are not efficient. Some coumarins
      possess antiplatelet activity and, due to their additional antioxidant effects,
      may be promising drugs for use in combination with the present therapeutic
      agents. The aim of this study was to analyse a series of simple 4-methylcoumarins
      for their antiplatelet activity. Human plasma platelet suspensions were treated
      with different aggregation inducers [arachidonic acid (AA), collagen and ADP] in
      the presence of the 4-methylcoumarins. Complementary experiments were performed
      to explain the mechanism of action. 5,7-Dihydroxy-4-methylcoumarins, in
      particular those containing a lipophilic side chain at C-3, reached the activity
      of acetylsalicylic acid on AA-induced aggregation. Other tested coumarins were
      less active. Some of the tested compounds mildly inhibited either collagen- or
      ADP-induced aggregation. 5,7-Dihydroxy-4-methylcoumarins did not interfere with
      the function of thromboxane synthase, but were competitive antagonists of
      thromboxane A(2) receptors and inhibited cyclooxygenase-1 as well. 5,7-Dihydroxy
      4-methylcoumarins appear to be promising candidates for the extension of the
      current spectrum of antiplatelet drugs.

PMID- 22996070
TI  - Fibrillation properties of human alpha1-acid glycoprotein.
AB  - Human alpha(1)-acid glycoprotein (AGP) is a positive acute phase plasma protein
      containing two disulfide bridges. Structural studies have shown that under
      specific conditions AGP undergoes aggregation. In this study, we analysed the
      nature of AGP's aggregates formed under reducing and non-reducing conditions at
      pH 5.5 and at relatively low temperatures. Thioflavin T and Congo red
      spectroscopic analyses indicated the presence of cross-beta structures in both
      unreduced and reduced AGP aggregates. In these samples amyloid-like fibrils were
      detected by transmission electron microscopy. The fibrils are branched and bent
      and present in very large amount in reduced AGP. Kinetics of AGP fibrillation
      proceeds without a lag phase and the rate constants of cross-beta formation are
      linearly dependent on AGP concentration and result higher under reducing
      conditions. The data suggest a possible downhill mechanism of polymerization with
      a first-order monomer concentration dependence. Bioinformatics tools highlighted
      an extended region that sheathes one side of the molecule containing aggregation
      prone regions. Reducing conditions make the extended region less constricted,
      allowing greater exposure of aggregation-prone regions, thus explaining the
      higher propensity of AGP to aggregate and fibrillate.

PMID- 22996071
TI  - Kinetic resolution of propargylamines via a highly enantioselective non-enzymatic
      N-acylation process.
AB  - The non-enzymatic kinetic resolution of diversely substituted primary propargylic
      amines is reported featuring a highly selective acetyl transfer using (1S,2S)- in
      conjunction with Aliquat(TM) 336, affording the corresponding enantio-enriched N
      acetylated propargylic amines with unprecedented levels of selectivity (s-factors
      of up to 193 at 50% conversion).

PMID- 22996072
TI  - The prevalence and patterns of intraluminal air in acute appendicitis at CT.
AB  - The purpose of this study is to investigate if the presence and distribution of
      intraluminal air in the appendix contributes to the computed tomography (CT)
      diagnosis of appendicitis. We identified 100 consecutive patients (57 men and 43
      women; mean age, 38) with CT prior to appendectomy for acute appendicitis over a
      5-year period and a control group of 100 consecutive patients (29 men and 71
      women; mean age, 39) who underwent CT for acute abdominal pain without
      appendicitis. Patients were scanned using multidetector row CT scanners at 1.25
      or 5-mm slice thickness, peak tube voltage of 120 kVp, and milliamperse
      automatically adjusted to attain a noise index of 12. Ninety-two of 100 study
      patients and 95 of 100 controls received 150 mL intravenous contrast. Two
      independent readers noted the presence and distribution pattern of intraluminal
      air in the appendix, appendiceal diameter, wall hyperemia, wall thickening (>3
      mm), and wall stratification and presence of any secondary signs of appendicitis
      including fat stranding and free fluid. Data were compared between groups using
      Fisher's exact test and Student's t test. Intraluminal air in the appendix was
      more common in control patients versus patients with appendicitis (66 of 100
      versus 27 of 100, p < 0.001). No significant differences in the patterns of
      intraluminal air were found between cases and controls. Among appendicitis cases,
      there was no significant difference in mean appendiceal diameter (12.8 versus
      12.0, p = 0.20) or number of CT signs of appendicitis (1.93 versus 1.86, p =
      0.78) in cases with intraluminal air versus without. No case of appendicitis
      demonstrated intraluminal air without secondary signs of appendicitis. Although
      intraluminal air is sometimes assumed to exclude a diagnosis of appendicitis, it
      is actually a common finding seen in up to 27 % of cases at CT. The pattern of
      intraluminal air was not helpful in differentiating a normal appendix from
      appendicitis.

PMID- 22996073
TI  - The breast reconstruction satisfaction questionnaire (BRECON-31): an affirmative
      analysis.
AB  - OBJECTIVE: To verify the subscale structure of the BRECON-31 using a test sample
      of women naive to the questionnaire. METHODS: The BRECON-31 was administered to
      women following breast reconstruction. Their responses were subjected to
      principal components analysis (PCA) with a varimax rotation. Components were
      maintained with an Eigenvalue greater than one. Internal consistency reliability
      was measured with Cronbach's Alpha (CA). Components on the test pool analysis
      were then compared with the subscales developed on 128 women who completed the
      questionnaire during the development phase. RESULTS: Fifty women completed the
      BRECON-31. Development and test pools of women were similar across demographics,
      pathology, and surgical details, except the development sample was somewhat older
      (53 yo vs. 49 yo, P = 0.02). Using PCA, eight subscales again emerged: self
      image, arm concerns, intimacy, satisfaction, recovery, self-consciousness,
      expectations, and breast appearance. A nipple, and abdominal strength and
      appearance subscales also emerged. Forty-one of the 45 items loaded similarly in
      the development and test pools. Internal consistency reliability was high, with
      CA in the test pool equaling or exceeding CA in the development pool in the
      majority of the subscales. CONCLUSIONS: The BRECON-31 factor structure identified
      in the development pool was supported by the test pool, with similar reliability.

PMID- 22996074
TI  - Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug-drug
      interactions: a PharmacoVigilance study in France.
AB  - OBJECTIVE: Our aim was to characterize Adverse Drug Reactions (ADRs) related to
      drug-drug interactions (DDIs) related to involvement of cytochrome P450 (CYP450)
      isoenzymes in a pharmacovigilance database. METHODS: ADRs recorded by Midi
      Pyrenees PharmacoVigilance center (France) between 1 January and 31 August 2008
      were extracted from the French PharmacoVigilance Database (FPVD). RESULTS: Among
      the 1,205 reported ADRs, 16 (1.3 %), can be explained by involvement of CYP450
      isoenzymes (including 4 "serious"). All interactions involved CYP inhibitors,
      mainly for CYP3A4/5. CONCLUSION: The percentage of ADRs reported in the
      pharmacovigilance database and related to CYP450-induced DDIs appears to be
      relatively low (~ 1-2 %).

PMID- 22996075
TI  - New prescriptions of spironolactone associated with angiotensin-converting-enzyme
      inhibitors and/or angiotensin receptor blockers and their laboratory monitoring
      from 2001 to 2008: a population study on older people living in the community in
      Italy.
AB  - PURPOSE: To analyse, in older community-dwelling people living in Italy's
      Lombardy region, 8-year trends in new users of spironolactone co-prescribed with
      angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor
      blockers (ARBs); blood test monitoring; and independent predictors of appropriate
      blood test monitoring. METHODS: The region's administrative health database from
      2001 to 2008 was used to retrieve yearly frequencies of subjects aged 65+ who
      started this co-prescription. Multivariate analyses were adjusted for age, sex,
      local health unit, treatment with beta-blockers, drugs for diabetes, and
      polypharmacy (i.e., exposure to five or more different drugs). RESULTS: Only new
      users of spironolactone co-prescribed with ARBs increased from 2001 to 2008 (P <
      0.001). In the 6 months before starting the co-prescriptions 96 to 100% of
      patients measured serum creatinine (mean 99.3%), sodium (97.3%) and potassium
      (98.6%). Within 3 months of starting the co-prescriptions 96 to 99% of patients
      measured serum sodium (mean 97.3%) and potassium (98.6%), but on average only 48%
      of them (range 43 to 53%) measured serum creatinine, with an increase over time
      (odds ratio [change in regression per year] = 1.03, 95% CI 1.02-1.05, P < 0.001).
      At multivariate analysis polypharmacy was found to be the only independent
      predictor of such creatinine monitoring (P < 0.001). CONCLUSIONS: Our results
      support the need for greater awareness within the medical community of the
      potential renal toxicity of the association of spironolactone with ACE-Is and/or
      ARBs. Adequate short-term monitoring of serum creatinine in all older community
      dwelling people who receive such co-prescription is necessary in order to ensure
      safe usage of these medications.

PMID- 22996076
TI  - Prevention of vancomycin induced nephrotoxicity: a review of preclinical data.
AB  - PURPOSE: Several strategies have been proposed for the prevention of vancomycin
      induced nephrotoxicity. Here, we review available evidence supporting the
      respective strategies. METHOD: Data were collected by searching the Scopus,
      PubMed, and Medline databases and the Cochrane database of systematic reviews.
      The key words used as search terms were "vancomycin," "nephrotoxicity", "renal
      failure," "renal damage," "nephroprotective," "renoprotective", and "prevention."
      Prospective or retrospective observational animal studies that evaluated the
      effects of a modality for the prevention of vancomycin-induced nephrotoxicity was
      included. RESULTS AND CONCLUSION: Animal studies show beneficial effects of
      various antioxidants, such as erdosteine, vitamin E, vitamin C, N-acetylcysteine,
      caffeic acid phenethyl ester, and erythropoietin, in the prevention of vancomycin
      induced nephrotoxicity. However, before these agents can be used in clinical
      practice, their potential benefits must be confirmed in future randomized
      controlled human studies.

PMID- 22996077
TI  - Citalopram and cardiac toxicity.
AB  - PURPOSE: Citalopram is a selective serotonin reuptake inhibitor (SSRI)
      antidepressant that is widely used in clinical practice. Recent data have
      indicated that high therapeutic citalopram doses may cause electrocardiographic
      abnormalities, and the regulatory authorities have amended its licenced dosage.
      The present manuscript reviews the available data concerning citalopram and
      cardiac toxicity. METHODS: Published data concerning the cardiac effects of
      citalopram were ascertained, and clinical data were considered separately between
      adverse effects arising from therapeutic use versus toxicity in the setting of
      intentional overdose. RESULTS: The occurrence of electrocardiographic
      abnormalities has long been recognised as a complication of acute citalopram
      overdose; a dose-effect relationship for QT prolongation has been described in a
      number of large case series, including several cases of torsades de pointes. In
      contrast, few data indicate the occurrence of QT prolongation and arrhythmia
      after therapeutic doses, and a dose-effect relationship within the therapeutic
      range has only recently been established. Citalopram is more likely to cause QT
      prolongation in patients with metabolic disturbance or pre-existing cardiac
      disease. CONCLUSIONS: A dose-effect relationship for QT prolongation exists
      across a broad range of citalopram doses, such that caution must be exercised
      when prescribing high doses or if there are co-existent risk factors for QT
      effects. The available data illustrate how clinical toxicity data may offer an
      earlier signal of cardiac effects than ascertained from conventional
      pharmacovigilance methods.

PMID- 22996078
TI  - Bidirectional optical transportation and controllable positioning of
      nanoparticles using an optical nanofiber.
AB  - This work provides a technique allowing bidirectional optical transportation and
      controllable positioning of nanoparticles using two counter-propagating laser
      beams at a wavelength of 980 nm in an optical nanofiber. With the assistance of
      an evanescent wave at the fiber surface, particles suspended in water were
      trapped onto the fiber by a gradient force and then transported along the fiber
      by a scattering force. By changing the difference between the input laser powers
      coupled into two ends of the fiber with DeltaP = -10 to 10 mW, the magnitude and
      direction of the scattering force that acted on the particles were changed, and
      thus the transportation direction and velocity of the particles were controlled.
      According to these properties, the bidirectional optical transportation of the
      particles along the fiber can be realized by coupling different laser powers into
      the two ends of the fiber (DeltaP? 0 mW). At the same time, the transported
      particles can be controllably positioned on the fiber by coupling the same laser
      powers into the two ends of the fiber (DeltaP = 0 mW). The relationship between
      the transportation velocity of the particles and the input optical power
      difference was investigated. Experiments were conducted with a 910 nm diameter
      fiber and 713 nm diameter polystyrene (PS) particle suspensions to demonstrate
      the effectiveness of this method. The experimental results were interpreted by
      numerical simulation and theoretical analysis.

PMID- 22996081
TI  - The learning curve in transoral laser microsurgery for malignant tumors of the
      larynx and hypopharynx: parameters for a levelled surgical approach.
AB  - The goal of the study was to identify parameters helpful to define a learning
      curve for laser microsurgery (TLM). 587 patients with malignant tumors of larynx
      and hypopharynx treated with TLM were divided into groups depending on the number
      of interventions their surgeons had performed. Outcome measures were obtained for
      the number of revision surgeries and complications, rates for tumor-free margins,
      tumor relapse and disease-specific survival rates for early and advanced tumors,
      serving to evaluate their potential influence on the learning curve. Surgery of
      early tumors was not influenced by the grade of experience. For locally advanced
      tumors the learning curve was statistically related to the number of surgeries
      needed per patient (p = 0.018). The number of overall complications (p = 0.000)
      and the disease-specific survival rate (p = 0.019) was significantly lower in the
      "expert" group. The percentage of postoperative bleedings was similar between all
      groups. Tumor-free margins and tumor relapse were not influenced by experience.
      In TLM, a learning curve could be observed for locally advanced tumors.

PMID- 22996082
TI  - Systematic review and meta-analysis of the use of tranexamic acid in
      tonsillectomy.
AB  - Post-tonsillectomy haemorrhage is a serious complication that can lead to death
      despite the fact that tonsillectomy is one of the commonest procedures performed
      in otolaryngology. Post-operative haemorrhage can be reduced by a potent
      antifibrinolytic agent such as tranexamic acid (TXA). This systematic review aims
      to evaluate the role of TXA in tonsillectomy. Searches were performed on MEDLINE,
      EMBASE, Web of Science and the Cochrane Library. Study selection, data extraction
      and quality assessment were conducted independently by two reviewers. Mean
      difference (MD) in volume of blood loss was calculated with 95 % confidence
      interval (CI). Risk ratios (RR) with 95 % CI were computed using random effects
      for the risk of post-tonsillectomy haemorrhage. This review identified and
      included a total of seven studies. Two studies (n = 180) compared the effects of
      TXA on volume of blood loss. Meta-analysis of these studies showed a significant
      decrease in the mean blood loss of 32.72 ml (95 % CI -42.66 to -22.78, p <
      0.00001). Five studies (n = 1,670) compared the number of patients with post
      tonsillectomy haemorrhage between TXA and control groups. TXA does not reduce the
      number of patients with post-tonsillectomy haemorrhage significantly (RR = 0.51,
      95 % CI 0.25 to 1.07, p = 0.08). TXA led to a significant reduction of
      tonsillectomy blood loss volume but had no impact on the rate of patients with
      post-tonsillectomy haemorrhage. This systematic review demonstrated that most
      studies were conducted before 1980; therefore, a new, large and well-designed
      randomised controlled trial is needed to investigate the risks and benefits of
      TXA.

PMID- 22996083
TI  - The temporo-parietal fascial flap in extended transnasal endoscopic procedures:
      cadaver dissection and personal clinical experience.
AB  - Due to progressively expanded indications of endoscopic transnasal surgery,
      having different reconstructive options in the armamentarium becomes of paramount
      importance. We herein report our experience with the use of the temporo-parietal
      fascial flap after extended endoscopic procedures for malignancies of the clival
      and nasopharyngeal regions. We focus our report on the surgical anatomy of this
      flap and the technique for its intranasal transposition through an infratemporal
      corridor. The main steps of the procedure and anatomic landmarks were
      highlighted, thanks to previous cadaver dissection. Five patients underwent an
      extended endoscopic resection for malignant tumors: one with persistent clival
      chordoma, three with recurrent nasopharyngeal carcinomas, and 1 recurrent
      nasopharyngeal adenoid cystic carcinoma. In all patients a temporo-parietal
      fascial flap was harvested to protect critical structures or irradiated denuded
      bone. The Mean harvesting and hospitalization time were 120 min and 5 days,
      respectively. No major or minor complications were observed. Whenever local flaps
      are not available for oncologic reasons or previous surgery, the temporo-parietal
      fascial flap is a safe and relatively easy option to protect the residual skull
      base and critical structures such as the internal carotid artery and dura of the
      posterior cranial fossa, after extended endoscopic resections.

PMID- 22996084
TI  - Synthesis and self-association of double-helical AADD arrays.
AB  - The design and syntheses of four self-complementary oligomers that contain an
      underlying AADD hydrogen bond sequence are presented, and their self-association
      was examined in the solution and solid state. The molecular recognition between
      the two strands is highly sensitive to substitutions of their component
      heterocycles. Substitution with electron-donating and -withdrawing groups and the
      influence of preorganization has a large effect on the overall stabilities of the
      complexes studied. In particular, a wide range (>10(5) M(-1)) of stabilities with
      respect to substitutions at various positions in the AADD oligomers was
      demonstrated. In the most extreme case, the dimerization constant measured
      (K(dimer) >=4.5*10(7) M(-1)) is comparable to the most stable homodimers of
      neutral AADD arrays reported to date.

PMID- 22996085
TI  - Systemic beneficial effects of Euphorbia besides its immunosuppressive effects.

PMID- 22996086
TI  - Fluence map optimization (FMO) with dose-volume constraints in IMRT using the
      geometric distance sorting method.
AB  - A new heuristic algorithm based on the so-called geometric distance sorting
      technique is proposed for solving the fluence map optimization with dose-volume
      constraints which is one of the most essential tasks for inverse planning in
      IMRT. The framework of the proposed method is basically an iterative process
      which begins with a simple linear constrained quadratic optimization model
      without considering any dose-volume constraints, and then the dose constraints
      for the voxels violating the dose-volume constraints are gradually added into the
      quadratic optimization model step by step until all the dose-volume constraints
      are satisfied. In each iteration step, an interior point method is adopted to
      solve each new linear constrained quadratic programming. For choosing the proper
      candidate voxels for the current dose constraint adding, a so-called geometric
      distance defined in the transformed standard quadratic form of the fluence map
      optimization model was used to guide the selection of the voxels. The new
      geometric distance sorting technique can mostly reduce the unexpected increase of
      the objective function value caused inevitably by the constraint adding. It can
      be regarded as an upgrading to the traditional dose sorting technique. The
      geometry explanation for the proposed method is also given and a proposition is
      proved to support our heuristic idea. In addition, a smart constraint
      adding/deleting strategy is designed to ensure a stable iteration convergence.
      The new algorithm is tested on four cases including head-neck, a prostate, a lung
      and an oropharyngeal, and compared with the algorithm based on the traditional
      dose sorting technique. Experimental results showed that the proposed method is
      more suitable for guiding the selection of new constraints than the traditional
      dose sorting method, especially for the cases whose target regions are in non
      convex shapes. It is a more efficient optimization technique to some extent for
      choosing constraints than the dose sorting method. By integrating a smart
      constraint adding/deleting scheme within the iteration framework, the new
      technique builds up an improved algorithm for solving the fluence map
      optimization with dose-volume constraints.

PMID- 22996087
TI  - The performance of functional methods for correcting non-Gaussian measurement
      error within Poisson regression: corrected excess risk of lung cancer mortality
      in relation to radon exposure among French uranium miners.
AB  - A broad variety of methods for measurement error (ME) correction have been
      developed, but these methods have rarely been applied possibly because their
      ability to correct ME is poorly understood. We carried out a simulation study to
      assess the performance of three error-correction methods: two variants of
      regression calibration (the substitution method and the estimation calibration
      method) and the simulation extrapolation (SIMEX) method. Features of the
      simulated cohorts were borrowed from the French Uranium Miners' Cohort in which
      exposure to radon had been documented from 1946 to 1999. In the absence of ME
      correction, we observed a severe attenuation of the true effect of radon
      exposure, with a negative relative bias of the order of 60% on the excess
      relative risk of lung cancer death. In the main scenario considered, that is,
      when ME characteristics previously determined as most plausible from the French
      Uranium Miners' Cohort were used both to generate exposure data and to correct
      for ME at the analysis stage, all three error-correction methods showed a
      noticeable but partial reduction of the attenuation bias, with a slight advantage
      for the SIMEX method. However, the performance of the three correction methods
      highly depended on the accurate determination of the characteristics of ME. In
      particular, we encountered severe overestimation in some scenarios with the SIMEX
      method, and we observed lack of correction with the three methods in some other
      scenarios. For illustration, we also applied and compared the proposed methods on
      the real data set from the French Uranium Miners' Cohort study.

PMID- 22996088
TI  - Pelvic examinations under anesthesia: a teachable moment.

PMID- 22996089
TI  - Patient safety strategies: are we on the same team?

PMID- 22996090
TI  - Pregnancy outcomes in women with and without gestational diabetes mellitus
      according to the International Association of the Diabetes and Pregnancy Study
      Groups criteria.
AB  - OBJECTIVE: To estimate the incidence of gestational diabetes mellitus (GDM)
      according to The International Association of the Diabetes and Pregnancy Study
      Groups (IADPSG) criteria and the pregnancy complications in women fulfilling
      these criteria but who are not considered diabetic according to the Canadian
      Diabetes Association criteria. METHODS: We estimated the rate of GDM according to
      the IADPSG criteria from November 2008 to October 2010. Then, we conducted a
      chart review to compare maternal and neonatal outcomes between women classified
      as GDM according to the IADPSG criteria but not by the Canadian Diabetes
      Association criteria (group 1; n=186) and nondiabetic women according to both
      criteria (group 2; n=372). Results were expressed as crude (odds ratio [OR]) or
      adjusted OR and 95% confidence interval (CI). The study has a statistical power
      of 80% to detect a difference between 16% and 8% in large for gestational age
      newborns (alpha level of 0.05; two-tailed). RESULTS: The rate of GDM using the
      IADPSG criteria was 27.51% (95% CI 25.92-29.11). Group 1 presented similar rates
      of large-for-gestational-age newborns (9.1% compared with 5.9%, adjusted OR 1.58,
      95% CI 0.79-3.13; P=.19), delivery complications (37.1% compared with 30.1%, OR
      1.37, 95% CI 0.95-1.98; P=.10), preeclampsia (6.5% compared with 2.7%, adjusted
      OR 2.40, 95% CI 0.92-6.27; P=.07), prematurity (6.5% compared with 2.7%, OR 1.10,
      95% CI 0.53-2.27; P=.85), neonatal complications at delivery (13.4% compared with
      9.7%, OR 1.45, 95% CI 0.84-2.49; P=.20), and metabolic complications (10.8%
      compared with 14.2%, OR 0.73, 95% CI 0.42-1.26; P=.29) compared with group 2.
      CONCLUSION: Women classified as nondiabetic by the Canadian Diabetes Association
      Criteria but considered GDM according to the IADPSG criteria have similar
      pregnancy outcomes as women without GDM. More randomized studies with cost
      effectiveness analyses are needed before implementation of these criteria. LEVEL
      OF EVIDENCE: II.

PMID- 22996091
TI  - Natural history of placenta previa in twins.
AB  - OBJECTIVE: To estimate the incidence of placenta previa in twin pregnancies
      compared with singletons and to estimate the rate and gestational age of previa
      resolution in twin pregnancies. METHOD: This was a retrospective cohort of
      singleton and twin pregnancies undergoing ultrasonography at 15-22 weeks of
      gestation and of twin pregnancies undergoing serial ultrasonography from 15 to 40
      weeks of gestation. Groups were defined by singleton or twin gestation and by
      chorionicity of twin gestation. The primary outcomes were incidence of placenta
      previa in each group and the percentage of all previa resolving at 24-28, 28-32,
      32-36, and 36 or more weeks of gestation. RESULTS: Of 67,895 pregnancies
      included, 2.1% (1,381 of 65,701) of singleton and 2.5% (56 of 2,194) of twin
      pregnancies had previa diagnosed (P=.15). Dichorionic twins had an increased risk
      of placenta previa compared with singletons (adjusted odds ratio 1.54, 95%
      confidence interval 1.15-2.06) or monochorionic twin pregnancies (relative risk
      3.29, 95% confidence interval 1.32-8.21). Of the 1,738 twin pregnancies with
      serial ultrasound examinations, 51 (2.9%) were noted to have previa. Sixty-nine
      percent of the previa resolved by 32 weeks, at between 32 and 36 weeks an
      additional 47% of the remaining previa resolved, and no previa resolved after 36
      weeks. CONCLUSION: Dichorionic twin pregnancies are at significantly increased
      risk for ultrasound-diagnosed previa when compared with singleton or
      monochorionic pregnancies. Among twin pregnancies with previa diagnosed in the
      second trimester, the majority of cases resolve by 32 weeks. LEVEL OF EVIDENCE:
      II.

PMID- 22996092
TI  - Hydramnios in twin gestations.
AB  - OBJECTIVE: To estimate the effect of hydramnios on pregnancy outcomes in
      dichorionic and monochorionic twins. METHODS: This is a retrospective cohort
      study of women with twin pregnancies who underwent ultrasound evaluation between
      1997 and 2010 and delivered liveborn neonates or stillborn fetuses at 24 weeks of
      gestation or more at a single institution. Hydramnios was defined as a single
      deepest pocket of amniotic fluid of at least 8 cm, and it was further categorized
      as mild (8-9.9 cm), moderate (10-11.9 cm), or severe (12 cm or more). The
      greatest degree of hydramnios identified during pregnancy was used for analysis.
      Monoamniotic pregnancies and pregnancies complicated by twin-twin transfusion
      syndrome were excluded. Anomalous neonates and stillborn fetuses were analyzed
      separately. RESULTS: Of 1,951 twin pregnancies, 1,311 were dichorionic (67%) and
      640 were monochorionic (33%). Hydramnios was identified in 348 pregnancies (18%).
      Major anomalies were more common with increasing hydramnios in both dichorionic
      and monochorionic twins (P<.001), with anomaly prevalence nearly 20% in cases of
      severe hydramnios. Severe hydramnios was significantly associated with stillbirth
      in monochorionic gestations (3 of 11, 27%, P<.001). Hydramnios was not associated
      with preterm delivery, fetal growth restriction, neonatal intensive care unit
      admission, or neonatal death in either dichorionic or monochrorionic pregnancies.
      CONCLUSION: Hydramnios is common in twins, occurring in one of six dichorionic
      and monochorionic pregnancies. Anomaly prevalence increased with degree of
      hydramnios; in monochorionic gestations, severe hydramnios was associated with
      risk of stillbirth. Despite this, adverse outcomes do not appear to be more
      frequent in the setting of hydramnios in twin getstaions. LEVEL OF EVIDENCE: II.

PMID- 22996093
TI  - Use and safety of Kielland's forceps in current obstetric practice.
AB  - OBJECTIVE: We sought to evaluate the use and safety of Kielland's rotational
      forceps for delivery in current obstetric practice at a tertiary care obstetric
      unit. METHODS: Data were obtained pertaining to all such attempted deliveries
      from 1997 through 2011. The outcomes analyzed included maternal obstetric
      features, induction and duration of labor, use of analgesia, fetal position and
      station, birth weight, seniority of the obstetrician, success and failure rates,
      and associated maternal and neonatal morbidity. RESULTS: There were 144 cases, of
      which 129 resulted in successful vaginal delivery (89.6%) and 15 were
      unsuccessful (10.4%). A senior obstetrician was present at all deliveries. The
      maternal morbidity was relatively low: third-degree or fourth-degree tear less
      than 1%, postpartum hemorrhage 12.4%, and urinary incontinence 7.8%. There were
      no cases of forceps-related neonatal trauma or hypoxic-ischemic encephalopathy.
      CONCLUSION: Contrary to earlier reports, in these circumstances, use of
      Kielland's forceps is associated with a high successful delivery rate and
      apparently low maternal and neonatal morbidity. LEVEL OF EVIDENCE: III.

PMID- 22996094
TI  - Acceptance and compliance with postpartum human papillomavirus vaccination.
AB  - OBJECTIVE: Despite the efficacy of vaccines against human papillomavirus (HPV),
      vaccination rates remain low in many countries. We estimated the acceptability
      and satisfaction of HPV vaccination in postpartum women. METHODS: Postpartum
      women aged 18-26 years were offered the quadrivalent HPV vaccine. Women were
      vaccinated during hospitalization after delivery, at the 6-week postpartum visit,
      and at a third dedicated vaccination visit. The primary outcome was completion of
      all three vaccinations. Secondary outcomes included the influence of knowledge
      and attitudes of HPV, decisional conflict, and satisfaction. RESULTS: A total of
      150 women were enrolled. Overall, seven (4.7%) women did not receive any doses of
      the vaccine, 62 (41.3%) received one dose, 35 (23.3%) received two doses, and 46
      (30.7%) completed the series and received all three doses of the vaccine.
      Knowledge of HPV and HPV-related disease, attitudes about HPV, and decisional
      conflict were not associated with completion of the vaccine series (P>.05). The
      vaccine was well tolerated with few side effects. The majority of women reported
      a high degree of satisfaction with postpartum vaccination; 97.2% thought
      vaccination was worthwhile, 98.6% thought postpartum vaccination was convenient,
      and 99.3% were happy they participated. Furthermore, 50.4% of women reported that
      they would not have otherwise asked about vaccination. After vaccination, only
      17.5% said they would have rather made a separate trip for vaccination.
      CONCLUSION: A strategy of postpartum HPV vaccination is convenient and associated
      with a high degree of patient satisfaction. LEVEL OF EVIDENCE: II.

PMID- 22996095
TI  - Trends in contraceptive use among women with human immunodeficiency virus.
AB  - OBJECTIVE: To estimate trends in contraceptive use, especially long-acting
      reversible contraceptives (LARCs) and condoms, among human immunodeficiency virus
      (HIV)-seropositive and HIV-seronegative women. METHODS: Human immunodeficiency
      virus-seropositive and HIV-seronegative women in a multicenter longitudinal
      cohort were interviewed semiannually between 1998 and 2010 about sexual behaviors
      and contraceptive use. Trends in contraceptive use by women aged 18-45 years who
      were at risk for unintended pregnancy but not trying to conceive were analyzed
      using generalized estimating equations. RESULTS: Condoms were the dominant form
      of contraception for HIV-seropositive women and showed little change across time.
      Less than 15% of these women used no contraception. Between 1998 and 2010, LARC
      use increased among HIV-seronegative women from 4.8% (6 of 126) to 13.5% (19 of
      141, P=.02), but not significantly among seropositive women (0.9% [4 of 438] to
      2.8% [6 of 213], P=.09). Use of highly effective contraceptives, including pills,
      patches, rings, injectable progestin, implants, and intrauterine devices, ranged
      from 15.2% (53 of 348) in 1998 to 17.4% (37 of 213) in 2010 (P=.55). Human
      immunodeficiency virus-seronegative but not HIV-seropositive LARC users were less
      likely than nonusers to use condoms consistently (hazard ratio 0.51, 95%
      confidence interval [CI] 0.32-0.81, P=.004 for seronegative women; hazard ratio
      1.09, 95% CI 0.96-1.23 for seropositive women). CONCLUSION: Although most HIV
      seropositive women use contraception, they rely primarily on condoms and have not
      experienced the increase in LARC use seen among seronegative women. Strategies to
      improve simultaneous use of condoms and LARC are needed to minimize risk of
      unintended pregnancy as well as HIV transmission and acquisition of sexually
      transmitted infections. LEVEL OF EVIDENCE: II.

PMID- 22996097
TI  - Incidental bartholin gland cysts identified on pelvic magnetic resonance imaging.
AB  - OBJECTIVE: To estimate the prevalence of Bartholin gland cysts in asymptomatic
      women serving as control participants who underwent pelvic magnetic resonance
      imaging (MRI) as part of research studies. The secondary aim was to investigate
      potential demographic characteristics associated with Bartholin gland cysts.
      METHODS: Pelvic MRIs from 430 control participants enrolled in five research
      projects were evaluated. All images were evaluated by at least two authors. The
      presence, laterality, and size of Bartholin gland cysts were recorded.
      Demographic information for each participant was obtained at the time of
      enrollment in the respective parent study. RESULTS: Approximately 3% of the
      participants had visible Bartholin gland cysts on MRI scans. Fifty percent of the
      cysts were identified on the right side, 42.9% were seen on the left side, and
      7.1% were bilateral. The cysts were, on average, 1.3*1.2*1.3 cm with dimensions
      ranging from 0.5 to 2.7 cm. There were no demographic differences between women
      with and without visible Bartholin gland cysts. CONCLUSION: Bartholin gland cysts
      occur in 3% of adult women. The cysts affect women of broad ranges of age and
      parity. Women with visible Bartholin gland cysts are demographically similar to
      women without cysts on pelvic imaging. LEVEL OF EVIDENCE: II.

PMID- 22996096
TI  - Negative predictive value of pap testing: implications for screening intervals
      for women with human immunodeficiency virus.
AB  - OBJECTIVE: To estimate the accuracy of Pap testing for women who are human
      immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive
      value. METHODS: Participants in the Women's Interagency HIV Study were monitored
      with conventional Pap tests every 6 months. After excluding those with abnormal
      Pap test results before study, cervical disease, or hysterectomy, women with
      negative enrollment Pap test results were monitored for development of precancer
      within 15 or 39 months, defined as a Pap test result read as high-grade squamous
      intraepithelial lesion, atypical glandular cells favor neoplasia, or
      adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial
      neoplasia 2 or worse. Correlations between one or more consecutive negative Pap
      test results and subsequent precancer were assessed using Cox proportional
      hazards models. RESULTS: Among 942 HIV-infected women with negative baseline Pap
      test results, eight (1%) developed precancer within 15 months and 40 (4%) within
      39 months. After three consecutive negative Pap test results, precancer was rare,
      with no cases within 15 months and 10 of 539 (2%) within 39 months. No women
      developed precancer or cancer within 39 months after 10 consecutive negative Pap
      test results. Risks for precancer within 15 months after negative Pap test result
      included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval
      [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1
      2.1 for women aged younger than 31 years compared with older than 45 years), and
      lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter,
      adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with
      CD4 more than 500/microliter). CONCLUSION: Annual Pap testing appears safe for
      women infected with HIV; for those with serial negative tests, longer intervals
      are appropriate. LEVEL OF EVIDENCE: II.

PMID- 22996098
TI  - Objective structured assessment of technical skills evaluation of theoretical
      compared with hands-on training of shoulder dystocia management: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare the skills of performing a shoulder dystocia management
      algorithm after hands-on training compared with demonstration. METHODS: We
      randomized medical students to a 30-minute hands-on (group 1) and a 30-minute
      demonstration (group 2) training session teaching a standardized shoulder
      dystocia management scheme on a pelvic training model. Participants were tested
      with a 22-item Objective Structured Assessment of Technical Skills scoring system
      after training and 72 hours thereafter. Objective Structured Assessment of
      Technical Skills scores were the primary outcome. Performance time, self
      assessment, confidence, and global rating scale were the secondary outcomes.
      Statistics were performed using Mann-Whitney U test, chi test, and multiple
      linear regression analysis. RESULTS: Two hundred three participants were
      randomized. Objective Structured Assessment of Technical Skills scores were
      significantly higher in group 1 (n=103) compared with group 2 (n=100) (17.95+/
      3.14 compared with 15.67+/-3.18, respectively; P<.001). The secondary outcomes
      global rating scale (GRS; 10.94+/-2.71 compared with 8.57+/-2.61, respectively;
      P<.001), self-assessment (3.15+/-0.94 compared with 2.72+/-1.01; P=.002), and
      confidence (3.72+/-0.98 compared with 3.34+/-0.90, respectively; P=.005), but not
      performance time (3:19+/-0:48 minutes compared with 3:31+/-1:05 minutes; P=.1),
      were also significantly different, favoring group 1. After 72 hours, Objective
      Structured Assessment of Technical Skills scores were still significantly higher
      in group 1 (n=67) compared with group 2 (n=60) (18.17+/-2.76 compared with
      14.98+/-3.03, respectively; P<.001) as were GRS (10.80+/-2.62 compared with
      8.15+/-2.59; P<.001) and self assessment (SA; 3.44+/-0.87 compared with 2.95+/
      0.94; P=.003). In a multiple linear regression analysis, group assignment (group
      1 compared with 2; P<.001) and sex (P=.002) independently influenced Objective
      Structured Assessment of Technical Skills scores. CONCLUSION: Hands-on training
      helps to achieve a significant improvement of shoulder dystocia management on a
      pelvic training model. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov,
      NCT01618565. LEVEL OF EVIDENCE: I.

PMID- 22996100
TI  - Cardiovascular outcomes after preeclampsia or eclampsia complicated by myocardial
      infarction or stroke.
AB  - OBJECTIVE: To assess the relationship between preeclampsia or eclampsia and
      stroke, myocardial infarction (MI), subsequent cardiovascular outcomes, and long
      term survival. METHODS: Using the Myocardial Infarction Data Acquisition System
      in New Jersey (1994-2009), we analyzed cardiovascular outcomes in women with and
      without preeclampsia or eclampsia and a first MI or stroke but with a
      hospitalization for a first MI or stroke (analysis 1: MI case group, n=57; MI
      control group, n=155; stroke case group, n=132; stroke control group, n=379). We
      also compared these outcomes in women with preeclampsia or eclampsia and a first
      MI or stroke during pregnancy with women with preeclampsia or eclampsia without
      MI or stroke during pregnancy (analysis 2: MI case group, n=23; MI control group,
      n=67; stroke case group, n=90; stroke control group, n=263). A subsequent
      occurrence of MI, stroke, and cardiovascular death, as well as a combined
      cardiovascular outcome, was ascertained. RESULTS: In analysis 1, women with
      preeclampsia or eclampsia were at significantly lower risk for combined
      cardiovascular outcome with all deaths (frequency of outcome 16.7%) and with
      cardiovascular deaths (10.6%) compared with women without preeclampsia or
      eclampsia after a first stroke (33.8% and 23.5%, respectively). In analysis 2,
      women with preeclampsia or eclampsia and a first stroke during admission were at
      significantly higher risk of all death (11.1%) and the combined cardiovascular
      outcome with all deaths (11.1%) compared with women with preeclampsia or
      eclampsia without a stroke (1.9% and 2.7%, respectively) during that admission.
      CONCLUSION: Our study indicates that preeclampsia or eclampsia not complicated by
      MI or stroke during pregnancy may not confer a very high risk for subsequent MI
      and stroke in up to 16 years of follow-up. Our data suggest that other known risk
      factors put women at greater risk for stroke than preeclampsia or eclampsia
      complicated by a stroke. LEVEL OF EVIDENCE: II.

PMID- 22996101
TI  - Sexual function in older women after oophorectomy.
AB  - OBJECTIVE: To compare the sexual function of older women who had bilateral
      oophorectomy with that of older women who had retained their ovaries. METHODS:
      This cross-sectional study involved analysis of 1,352 women aged 57 to 85 years
      from the National Social Life, Health, and Aging Project. Women with previous
      bilateral oophorectomy were compared with women who retained their ovaries. The
      primary outcome of interest was self-report of sexual ideation, chosen because
      having thoughts about sexual experiences is not prohibited by either a partner or
      a woman's own physical limitations. RESULTS: Three hundred fifty-six (25.8%)
      women reported previous bilateral oophorectomy. Our analysis achieved 90% power
      to detect a difference of 10% in sexual ideation. No significant difference in
      the report of sexual ideation was found between women with previous bilateral
      oophorectomy and women who retained their ovaries (54.5% and 95% confidence
      interval [CI] 48.1-61.0 compared with 49.9% and 95% CI 45.3-54.5, P=.230), even
      after adjusting for current hormone therapy, age, education, and race (adjusted
      odds ratio 1.32, 95% CI 0.96-1.80). CONCLUSION: Bilateral oophorectomy may not
      play a pivotal role in sexual ideation and function among older women. LEVEL OF
      EVIDENCE: II.

PMID- 22996099
TI  - The utility of uterine artery Doppler velocimetry in prediction of preeclampsia
      in a low-risk population.
AB  - OBJECTIVE: The underlying pathophysiology of preeclampsia is thought to be
      abnormal trophoblast invasion of the spiral arteries leading to maldevelopment of
      uteroplacental perfusion. We estimated whether uterine artery Doppler
      measurements made in the early second trimester would predict the subsequent
      development of preeclampsia. METHODS: Uterine artery Doppler measurements before
      21 weeks of gestation (median 16.6 weeks) were correlated with subsequent
      development of preeclampsia in a cohort of 2,188 low-risk nulliparous women in a
      randomized control trial of antioxidant supplementation for prevention of
      preeclampsia. Preeclampsia developed in 165 (7.5%) women. RESULTS: Development of
      preeclampsia overall was associated with increased resistance index, pulsatility
      index, a pulsatility index or resistance index multiple of the median at or above
      the 75th percentile but not the presence of a notch or a bilateral notch before
      21 weeks of gestation. The sensitivity was 43% (95% confidence interval [CI] 35
      51) and specificity 67% (95% CI 65-69) for prediction of preeclampsia overall.
      The presence of a notch or bilateral notch, resistance index, and pulsatility
      index multiple of the median was significantly associated with early onset
      (before 34 weeks of gestation) compared with late onset or no preeclampsia (odds
      ratio [OR] 6.9, 95% CI 2.3-20.9; sensitivity 78%, 95% CI 52-94; specificity 66%,
      95% CI 64-68). The presence of a notch or resistance index multiple of the median
      at or above the 75th percentile increased the odds of developing severe compared
      with mild or no preeclampsia (OR 2.2, 95% CI 1.4-3.7; sensitivity 53%, 95% CI 40
      65; specificity 66%, 95% CI 64-68). CONCLUSION: Our data show poor sensitivity of
      second-trimester Doppler ultrasound measurements for prediction of preeclampsia
      overall in a well-characterized, low-risk, nulliparous population. The technique
      has utility in identifying poor trophoblast invasion of spiral arteries of a
      magnitude that severely compromises uteroplacental blood flow and gives early
      onset disease. LEVEL OF EVIDENCE: II.

PMID- 22996103
TI  - Assisted reproductive technology and major birth defects in Western Australia.
AB  - OBJECTIVE: To estimate the prevalence of major birth defects diagnosed by 6 years
      of age in all births and terminations of pregnancy for fetal anomaly conceived by
      assisted reproductive technology (when this included intracytoplasmic sperm
      injection and in vitro fertilization [IVF]) and the remainder of nonassisted
      reproductive technology-conceived children born in Western Australia from 1994 to
      2002. METHODS: This retrospective cohort study used data linkage between three
      population-based registers (Reproductive Technology Register, Western Australian
      Register of Developmental Anomalies, and Midwives' Notification of Birth System)
      to identify all assisted reproductive technology (n=2,911) and nonassisted
      reproductive technology (n=210,997) births with and without birth defects
      diagnosed by age 6 and all terminations of pregnancy for fetal anomaly. RESULTS:
      A major birth defect was diagnosed in 8.7% of assisted reproductive technology
      and 5.4% of nonassisted reproductive technology singletons (odds ratio [OR] 1.53,
      95% confidence interval [CI] 1.30-1.79), as well as 7.1% of assisted reproductive
      technology twins and 5.9% of nonassisted reproductive technology twins of unlike
      sex (OR 1.08, 95% CI 0.77-1.51). The prevalence of birth defects in assisted
      reproductive technology singletons and twins decreased markedly over the study
      period. This change was evident across all three clinics contributing data over
      the whole study and was particularly marked for children conceived as a result of
      IVF. CONCLUSION: There has been a decrease in the prevalence of birth defects
      over time in children born as a result of assisted reproductive technology in
      Western Australia; however, the prevalence of major birth defects in assisted
      reproductive technology singletons remains increased compared with nonassisted
      reproductive technology singletons. LEVEL OF EVIDENCE: II.

PMID- 22996102
TI  - Trends and correlates of good perinatal outcomes in assisted reproductive
      technology.
AB  - OBJECTIVE: To estimate trends in good perinatal outcomes (singleton live births
      at term with birthweight more than 2,500 g) among live births after assisted
      reproductive technology in the United States from 2000 to 2008, and associated
      factors among singletons in 2008. METHODS: Using retrospective cohort data from
      the National Assisted Reproductive Technology Surveillance System from 2000 to
      2008, we calculated relative change and chi tests for trend in the proportion of
      good perinatal outcomes among assisted reproductive technology live births
      (n=444,909) and liveborn singletons (n=222,500). We conducted univariable
      analyses followed by multiple logistic regression to estimate the effects of
      various characteristics on the outcome among singletons born in 2008 after fresh,
      nondonor assisted reproductive technology cycles (n=20,780). RESULTS: The
      proportion of good perinatal outcomes among all liveborn neonates increased from
      38.6% in 2000 to 42.5% in 2008, whereas it declined marginally among singletons
      from 83.6% to 83.4%. One previous birth, transfer of fewer than three embryos,
      and the presence of fewer than three fetal hearts on 6-week ultrasound
      examination were associated with good perinatal outcome among singletons. Non
      Hispanic black race, tubal factor infertility, uterine factor infertility,
      ovulatory disorder, and 5-day embryo culture were associated with reduced odds
      for a good outcome. The strongest association was the presence of one fetal heart
      compared with more than two (adjusted odds ratio 2.43, 95% confidence interval
      1.73-3.42). CONCLUSION: From 2000 to 2008, good perinatal outcomes increased
      among assisted reproductive technology live births. Among singleton live births,
      odds for good outcome were greatest with the presence of a single fetal heart and
      lowest in women of non-Hispanic black race. LEVEL OF EVIDENCE: II.

PMID- 22996104
TI  - Minimally invasive endometrial ablation device complications and use outside of
      the manufacturers' instructions.
AB  - OBJECTIVE: To review the U.S. Food and Drug Administration (FDA) Manufacturer and
      User Facility Device Experience database for reports describing serious adverse
      events and adverse events reports describing use outside of the manufacturers'
      labeled instructions for the five FDA-approved minimally invasive endometrial
      ablation devices. METHODS: We queried the Manufacturer and User Facility Device
      Experience database for reports of device malfunction, patient injury, or death
      reported for each device from January 1, 2005 to December 31, 2011. We reviewed
      U.S. reports individually for annotations of patient injury or death and
      tabulated the reports by type of injury and device. We identified nine categories
      of serious injury (death, sepsis or bacteremia, intra-abdominal abscess, uterine
      rupture, thermal bowel injury, mechanical bowel injury, transmural uterine
      thermal injury, urologic injury, and lower genital tract or skin burns) and noted
      all reports citing device use outside of the manufacturers' labeled instructions.
      We also identified reports of hysterectomy or bowel resection attributable to an
      adverse event. RESULTS: Serious adverse events, including bowel injury (n=128),
      sepsis or bacteremia (n=47), intra-abdominal abscess (n=18), urologic injury
      (n=2), and uterine rupture (n=1) were reported. Death was also reported (n=4).
      Eight percent (66 of 829) of serious adverse events reports cited use outside of
      the manufacturers' labeled instructions, as did 7.3% (6 of 82) of reports citing
      need for hysterectomy and 8.7% (9 of 103) of reports of bowel resection.
      CONCLUSION: The findings from the Manufacturer and User Facility Device
      Experience database highlight the potential risk of serious complications related
      to endometrial ablation and underscore the importance of training in correct
      device use and familiarity with the manufacturer's labeled instructions. LEVEL OF
      EVIDENCE: III.

PMID- 22996105
TI  - Effect of radical cytoreductive surgery on omission and delay of chemotherapy for
      advanced-stage ovarian cancer.
AB  - OBJECTIVE: Cytoreductive surgery is associated with extensive morbidity and may
      delay chemotherapy. We examined the associations among cytoreduction,
      perioperative complications, and delay or omission of chemotherapy. METHODS:
      Women aged 65 years or older with stage III-IV ovarian cancer who were treated
      with surgery from 1991-2005 and recorded in the Surveillance, Epidemiology, and
      End Results-Medicare database were examined. We estimated the influence of
      extended cytoreduction as well as the occurrence of major perioperative
      complications on receipt and timing of chemotherapy and survival. RESULTS: Among
      3,991 patients, 479 (12%) failed to receive chemotherapy. Of those treated with
      chemotherapy, 2,527 (72%) initiated treatment within 6 weeks of surgery, 838
      (24%) within 6-12 weeks, and 147 (4%) more than 12 weeks after surgery. In a
      multivariable model, older patients, those with comorbidities, mucinous tumors,
      and stage IV neoplasms were more likely not to receive chemotherapy (P<.05).
      Extended cytoreduction and the occurrence of postoperative complications were not
      associated with omission of chemotherapy but were associated with chemotherapy
      delay. For every 14 patients who underwent one extended procedure and for every
      13 who had two extended procedures, one patient had a delay in receipt of
      chemotherapy. For every 14 patients who had one complication and for every four
      who had two complications, one patient had a delay in receipt of chemotherapy.
      The occurrence of more than two perioperative complications (hazard ratio 1.31,
      95% confidence interval [CI] 1.15-1.49) and initiation of chemotherapy more than
      12 weeks after surgery (hazard ratio 1.32, 95% CI 1.07-1.64) were associated with
      decreased survival. CONCLUSION: Extended cytoreductive surgery and perioperative
      complications significantly delay initiation but do not increase the chance of
      omission of chemotherapy for women with ovarian cancer. LEVEL OF EVIDENCE: II.

PMID- 22996106
TI  - Missed opportunities for preventing congenital syphilis infection in New York
      City.
AB  - OBJECTIVE: To describe health care providers' missed opportunities for preventing
      and treating congenital syphilis in New York City. METHODS: Review of congenital
      syphilis cases reported to the New York City Department of Health and Mental
      Hygiene from January 1, 2000 to December 31, 2009. Receipt and timing of prenatal
      care, serologic testing, and treatment of mothers and newborns were reviewed.
      Missed opportunities were defined as receipt of prenatal care plus one of the
      following: 1) lack of documented treatment for syphilis infection diagnosed
      before pregnancy; 2) absence of serologic testing during pregnancy; 3) late
      maternal treatment; 4) maternal treatment with a nonpenicillin regimen; or 5)
      lack of maternal treatment. RESULTS: In total, 195 newborns with congenital
      syphilis were born to 190 mothers with 191 pregnancies. Overall, 80% (95%
      confidence interval [CI] 74-86%, 152 of 190) of all mothers received prenatal
      care; 63% (95% CI 56-71%, 96 of 152) of these had one or more missed
      opportunities for prevention. Twelve mothers received inadequate treatment or no
      treatment during the case pregnancy for documented syphilis infection before
      pregnancy, and 42 mothers without previous syphilis diagnosis did not have
      serologic testing during the case pregnancy. Of 103 mothers with syphilis
      diagnosed before 30 weeks of gestation, 12 received late penicillin therapy, 27
      received no therapy, and 3 received inappropriate (nonpenicillin) therapy.
      Seventeen percent (95% CI 12-22%, 33 of 193) of liveborn newborns received no
      treatment during their hospitalization. CONCLUSION: Providers missed well-defined
      opportunities to prevent congenital syphilis for the majority of cases. Combined
      efforts to prevent future cases include provider education and better integration
      of care between obstetricians and pediatricians. LEVEL OF EVIDENCE: III.

PMID- 22996107
TI  - Screening women for oral contraception: can family history identify inherited
      thrombophilias?
AB  - OBJECTIVE: Screening for inherited thrombophilias with laboratory tests is
      impractical before starting women on combined oral contraceptives. As an
      alternative, some recommend eliciting a family history of venous thromboembolism.
      The validity of this approach, however, remains unclear. DATA SOURCES: We sought
      all published reports that correlated a family history of venous thromboembolism
      with any thrombophilia confirmed by laboratory test. We used sequential,
      overlapping computer searches including MeSH terms used for articles in PubMed, a
      narrative search phrase in Google Scholar, and then all "related" articles in
      PubMed for each article included without time or language limitations. This was
      supplemented by a search of www.clinicaltrials.gov. METHODS OF STUDY SELECTION:
      The search yielded 10 reports. Information was sought without success from
      corresponding authors of four other reports that may have had relevant data. Most
      reports studied atypical, high-prevalence referral populations. TABULATION,
      INTEGRATION, AND RESULTS: Results were presented according to the MOOSE (Meta
      analysis of observational studies in epidemiology) guidelines for systematic
      reviews of observational studies. The patient populations varied widely,
      definitions of family history included first- or first- and second-degree
      relatives, and the thrombophilias studied differed among these reports. Hence,
      aggregation of results was not possible. Despite these differences, all reports
      consistently documented poor validity of family history for detecting
      thrombophilias. Sensitivity ranged from 16% to 63% and positive predictive value
      from 6% to 50% for the various thrombophilias studied. In no study did family
      history meet the benchmark for a good test (sensitivity plus specificity greater
      than 150%). CONCLUSION: Obtaining a family history of venous thromboembolism
      before starting combined oral contraceptives is not a valid means to detect a
      woman's risk of thrombophilia. Even in high-prevalence populations, in which the
      positive predictive value is increased, a positive family history of venous
      thromboembolism was no better than flipping a coin in predicting thrombophilia.

PMID- 22996108
TI  - Newborn screening and the obstetrician.
AB  - Newborn screening is the largest genetic screening program in the United States
      with approximately four million newborns screened yearly. It has been available
      and in continuous development for more than 50 years. Each state manages, funds,
      and maintains its own individual program, which encompasses newborn screening as
      well as the diagnosis and coordination of care for affected infants and children.
      The ideal disorder for screening is one in which newborn intervention prevents
      later disabilities or death for infants who may appear normal at birth. There are
      31 core conditions that are currently recommended for incorporation into state
      screening programs. To obtain a sample, several drops of blood are collected from
      the newborn's heel and applied to filter paper. Although testing for core
      disorders is fairly standardized, more extensive screening varies by state and
      the rigorous evaluation of new disorders for inclusion in state screening panels
      is ongoing. As genomic medicine becomes more accessible, screening newborns for
      chronic diseases that may affect their long-term health will need to be addressed
      as well as the use of the residual blood spots for research. Obstetric providers
      should, at some time during pregnancy, review the basic process of newborn
      screening with parents to prepare them for this testing in the neonatal period.
      This information can be reviewed as it best suits incorporation in an
      individual's practice; verbal discussion and the distribution of written
      materials with resources for further information are encouraged.

PMID- 22996109
TI  - Advocacy and the importance of supporting patients beyond the examination room.

PMID- 22996110
TI  - False alarms and pseudo-epidemics: the limitations of observational epidemiology.
AB  - Most reported associations in observational clinical research are false, and the
      minority of associations that are true are often exaggerated. This credibility
      problem has many causes, including the failure of authors, reviewers, and editors
      to recognize the inherent limitations of these studies. This issue is especially
      problematic for weak associations, variably defined as relative risks (RRs) or
      odds ratios (ORs) less than 4. Such associations, commonly reported in the
      medical literature, are more likely to be attributable to bias than to causal
      association. All observational research has bias (which can include selection,
      information, and confounding bias). Hence, detection of small associations falls
      below the discriminatory ability of observational studies. In general, unless RRs
      in cohort studies exceed 2 to 3 or ORs in case-control studies exceed 3 or 4,
      associations in observational research findings should not be considered
      credible. However, these guidelines are not foolproof: strong (yet spurious)
      associations can result when large amounts of bias are present. Only in a
      properly performed randomized controlled trial, free of bias, should small
      associations merit attention. Better training and more circumspection on the part
      of investigators, tougher editorial standards on the part of journals, and hefty
      skepticism on the part of referees and readers are necessary to avoid the dangers
      of false alarms, pseudo-epidemics, and their unfortunate consequences.

PMID- 22996111
TI  - Maternal mortality, near misses, and severe morbidity: lowering rates through
      designated levels of maternity care.
AB  - An increase in the prevalence of obesity, hypertension, diabetes, and abnormal
      placentation, among others, has fueled the recent rise in maternal mortality,
      "near misses" and severe morbidity. In 1976, the March of Dimes published a
      report, "Toward Improving the Outcome of Pregnancy," which included
      recommendations for levels of perinatal care. Although the original intent was to
      address the needs of both mother and neonate, implementation in the ensuing years
      focused mostly on the latter. Currently, there are no well-defined nationally
      accepted levels of maternal care similar to those adopted by the American Academy
      of Pediatrics for neonatal intensive care units. When discussing regionalization
      of perinatal care, the needs of the mother are frequently overlooked. We propose
      that it is time to address this deficiency and develop levels of care that are
      specific to the mother. We expect that improving maternal care will also improve
      neonatal outcome. We call on various organizations and agencies to establish
      national standards and levels of maternity care much as our colleagues in
      neonatology have already successfully done. We canvassed the available
      publications by states and other countries and found a number of noteworthy
      examples. We propose that the goal would be an integrated maternal-fetal-neonatal
      care network, a model similar to what is done in stroke or emergency care. In
      addition to accepting transfers, the central facility functioning at the highest
      level would also be responsible for education, evidence-based best practices,
      policy development, and quality review and improvement within the network.

PMID- 22996112
TI  - New insights into the pathogenesis of ovarian carcinoma: time to rethink ovarian
      cancer screening.
AB  - Recent discoveries about the pathogenesis of ovarian cancer have suggested that
      it can no longer be thought of as a single entity, but that the histologically
      defined ovarian cancer subtypes are different diseases, with different precursor
      lesions and distinct biomarker expression profiles. Most serous carcinomas
      probably arise from the fallopian tube. Clear cell and endometrioid carcinomas
      are associated with endometriosis and likely originate from ectopic endometrium.
      The focus of large ovarian cancer screening trials has been detection of
      macroscopic ovarian abnormalities by ultrasonography and detection of serum
      biomarkers associated with the most common (serous) subtype of ovarian cancer.
      The only completed and phase three randomized controlled trial failed to achieve
      the objective of reducing ovarian cancer mortality and was not able to
      demonstrate a stage migration effect of the screening. Future screening
      strategies have to incorporate our growing understanding of each subtype of
      pelvic (ovarian or fallopian tube) cancer, its organ of origin, and disease
      specific biomarkers. We review how our current understanding of pathogenesis
      should prompt a reexamination of data from ovarian cancer screening studies and
      discuss potential designs for future screening strategies.

PMID- 22996113
TI  - Practicing pelvic examinations by medical students on women under anesthesia: why
      not ask first?

PMID- 22996114
TI  - Trouble voiding in an adolescent girl. Diagnosis: Obstruced hemivagina and
      ipsilateral renal anomaly syndrome.

PMID- 22996115
TI  - Perioperative evaluation in Herlyn-Werner-Wunderlich syndrome.
AB  - BACKGROUND: Herlyn-Werner-Wunderlich syndrome is defined by uterine didelphys,
      obstructed hemivagina, and ipsilateral renal agenesis. We report the
      presentation, radiographic findings, and outcomes of three patients with Herlyn
      Werner-Wunderlich syndrome who underwent surgical management at a tertiary care
      academic medical center. CASES: Two patients were diagnosed by magnetic resonance
      imaging and one by ultrasonography. All three underwent successful transvaginal
      septoplasty and drainage of the hematocolpos and hematometra. One required
      septoplasty revision with temporary vaginal stent placement. CONCLUSION: Herlyn
      Werner-Wunderlich syndrome is a rare condition. The most urgent concern is the
      obstruction of menstrual effluent. Unlike an isolated transverse vaginal septum,
      the vaginal septum with Herlyn-Werner-Wunderlich syndrome is parallel to the
      patent vaginal canal, less pliable, and closer to the cervix. These anatomical
      differences result in pronounced distortion with significant diagnostic and
      surgical challenges.

PMID- 22996116
TI  - What is new in minimally invasive surgery? Best articles from the past year.

PMID- 22996117
TI  - Cosmetic gynecology and the elusive quest for the "perfect" vagina.

PMID- 22996118
TI  - Cosmetic gynecology and the elusive quest for the "perfect" vagina.

PMID- 22996120
TI  - A survey of central association members about the definition, management, and
      complications of shoulder dystocia.

PMID- 22996125
TI  - Retraction: The following College document has been withdrawn: ACOG Committee
      Opinion No. 407: Low Bone Mass (Osteopenia) and Fracture Risk (Obstet Gynecol
      2008;111:1259-61).

PMID- 22996126
TI  - Practice bulletin no. 130:  prediction and prevention of preterm birth.

PMID- 22996127
TI  - Committee opinion no. 537:  reprocessed single-use devices.
AB  - The reprocessing and reuse of single-use instruments has become increasingly
      common. Although there are limited data on reprocessed single-use devices,
      existing studies have found a significant rate of physical defects, performance
      issues, or improper decontamination. There are currently no data in the medical
      literature of studies evaluating the cost-effectiveness of reprocessed single-use
      devices in gynecologic surgery. The use of a reprocessed single-use device
      provides no direct benefit to an individual patient or her physician. It is the
      operating surgeon's ethical responsibility to make a good faith effort to know
      whether reprocessed single-use devices are to be used, and to not use instruments
      if he or she has concerns about the quality or safety of the instrument(s).
      Studies on the safety, quality, and cost-effectiveness of reprocessed single-use
      devices in gynecologic surgery are needed. Physicians should be informed whether
      the instruments used in surgery are original or reprocessed, and adverse events
      should be reported to improve the safety information about reprocessed single-use
      devices.

PMID- 22996128
TI  - Committee opinion no. 538:  nonmedical use of prescription drugs.
AB  - The nonmedical use of prescription drugs, particularly opioids, sedatives, and
      stimulants, has been cited as epidemic in the United States, accounting for
      increasing numbers of emergency department visits and deaths from reactions and
      overdoses. The prevalence of prescription drug abuse is similar among men and
      women. Those who abuse prescription drugs most often obtain them from friends and
      family either through sharing or theft. Physicians should screen all patients
      annually and early in prenatal care with a validated questionnaire for the
      nonmedical use of prescription drugs. They should provide preventive education
      for all patients and referral for treatment, when psychologic or physical drug
      dependence is identified. Physicians should also educate patients in the proper
      use, storage, and disposal of prescription drugs.

PMID- 22996129
TI  - Committee opinion no. 539:  adolescents and long-acting reversible contraception:
      implants and intrauterine devices.
AB  - Long-acting reversible contraception (LARC)-intrauterine devices and the
      contraceptive implant-are safe and appropriate contraceptive methods for most
      women and adolescents. The LARC methods are top-tier contraceptives based on
      effectiveness, with pregnancy rates of less than 1% per year for perfect use and
      typical use. These contraceptives have the highest rates of satisfaction and
      continuation of all reversible contraceptives. Adolescents are at high risk of
      unintended pregnancy and may benefit from increased access to LARC methods.

PMID- 22996130
TI  - From mice to humans.
AB  - The genomes of many species have now been completely sequenced including human
      and mouse. Great progress has been made in understanding the complex genetics
      that underlie diabetes and obesity in human populations. One of the current
      challenges is the functional identification and characterization of the genes
      within loci that are being mapped. There are many approaches to this problem and
      this review outlines the valuable role that the mouse can play. We outline the
      mouse resources that are available to the research community, including knockouts
      with conditional potential for every gene, and the efforts of the International
      Mouse Phenotyping Consortium to attach phenotype information to these genes. We
      also briefly consider the potential of TALEN technology to tailor-make new mouse
      models of specific mutations discovered in humans. Finally, we consider the
      recent progress in characterizing the GWAS genes FTO, TCF7L2, CDKAL1, and SLC30A8
      in engineered mouse models.

PMID- 22996132
TI  - Gender differences in physical aggression and associated developmental correlates
      in a sample of Canadian preschoolers.
AB  - Recent studies have indicated that gender differences in children's aggressive
      behavior emerge during the preschool years and that these differences are
      relatively stable during childhood. The current study assesses whether these
      gender differences can be observed when a multidimensional measure of aggression
      from the ongoing Vancouver Longitudinal Study on the psychosocial development of
      children is utilized. Specifically, the level of physical aggression (PA) in
      three cohorts of children (aged three, four, and five years) from the initial 338
      families in the Wave I data recruited for this study was analyzed using a series
      of constrained and unconstrained latent class models. Three latent classes of
      physically aggressive children were identified (low, moderate, and high level),
      with boys being over-represented in the highly aggressive group and being five
      times more likely than girls to show high levels of aggression. No age effects
      were detected, suggesting gender differences from the age of three years onward.
      The correlates of PA were similar for both boys and girls. Particularly
      important, a small subgroup of highly aggressive boys emerged from the study
      showing a clinical profile similar to Moffitt's life-course-persistent antisocial
      pattern. Such a group was not identified for girls.

PMID- 22996133
TI  - Subtle impact of atomic ratio, charge and lewis basicity on structure selection
      and stability: the Zintl anion [(La@In2Bi11)(MU-Bi)2(La@In2Bi11)]6-.
AB  - Ternary intermetalloid cluster: the first intermetalloid M/13/15 Zintl anion
      [(La@In(2)Bi(11))(MU-Bi)(2)(La@In(2)Bi(11))](6-) was obtained upon reaction of
      [InBi(3)](2-) with [La(C(5)Me(4)H)(3)] in ethane-1,2-diamine. DFT calculations
      served to analyze and explain the Lewis acid/base interaction upon assignment of
      formal charges as "Bi(+) <-In(2-) ", which discriminates the anion from an
      isoelectronic La/Sn/Bi analogue that does not require bridging.

PMID- 22996131
TI  - Monogenic models: what have the single gene disorders taught us?
AB  - Monogenic diabetes constitutes a heterogeneous group of single gene disorders.
      The molecular background and clinical picture of many of these diseases have been
      described. While each of these forms is much less prevalent than multifactorial
      type 1 and type 2 diabetes mellitus (T2DM), together they affect millions of
      patients worldwide. Genetic diagnosis, which has become widely available, is of
      great clinical importance for patients with single gene diabetes. It helps to
      fully understand the pathophysiology of the disease, tailor the optimal
      hypoglycemic treatment, and define the prognosis for the entire family. Monogenic
      diabetes forms can be divided into 2 large groups, resulting from impaired
      insulin secretion or from an abnormal response to insulin. There are several
      lessons we have been taught by single-gene diabetes. We learned that the gene
      responsible for the occurrence of diabetes can be identified if an appropriate
      search strategy is used. In addition, discoveries of genes responsible for
      monogenic disorders pointed to them as susceptibility candidates for T2DM.
      Moreover, establishing that some families of proteins or biological pathways,
      such as transcription factors or potassium channel subunits, are involved in
      monogenic diabetes sparked research on their involvement in multifactorial
      diabetes. Finally, the example of single gene diabetes, particularly HNF1A MODY
      and permanent neonatal diabetes associated with the KCNJ11 and ABCC8 genes, all
      efficiently controlled on sulfonylurea, inspires us to continue the efforts to
      tailor individual treatment for T2DM patients. In this review paper, we summarize
      the impact of single gene disease discoveries on diabetes research and clinical
      practice.

PMID- 22996134
TI  - Reply.

PMID- 22996135
TI  - A case of sodium chlorite toxicity managed with concurrent renal replacement
      therapy and red cell exchange.
AB  - INTRODUCTION: Sodium chlorite is a powerful oxidizing agent with multiple
      commercial applications. We report the presentation and management of a single
      case of human toxicity of sodium chlorite. CASE REPORT: A 65-year-old man
      presented to hospital after accidentally ingesting a small amount of a sodium
      chlorite solution. His principal manifestations were mild methemoglobinemia,
      severe oxidative hemolysis, disseminated intravascular coagulation, and anuric
      acute kidney injury. He was managed with intermittent hemodialysis, followed by
      continuous venovenous hemofiltration for management of acute kidney injury and in
      an effort to remove free plasma chlorite. Concurrently, he underwent two red cell
      exchanges, as well as a plasma exchange, to reduce the burden of red cells
      affected by chlorite. These interventions resulted in the cessation of hemolysis
      with stabilization of serum hemoglobin and platelets. The patient survived and
      subsequently recovered normal renal function. DISCUSSION: This is only the second
      case of sodium chlorite intoxication reported in the medical literature and the
      first to report the use of renal replacement therapy in combination with red cell
      exchange in its management.

PMID- 22996136
TI  - The toxicology Tower of Babel: why we need to agree on a lexicon in prescription
      opioid research.

PMID- 22996137
TI  - Microtubule network is required for insulin-induced signal transduction and actin
      remodeling.
AB  - Both microtubule and actin are required for insulin-induced glucose uptake.
      However, the roles of these two cytoskeletons and their relationship in insulin
      action still remain unclear. In this work, we examined the morphological change
      of microtubule/actin and their involvement in insulin signal transduction using
      rat skeletal muscle cells. Insulin rapidly led to microtubule clustering from
      ventral to dorsal surface of the cell. Microtubule filaments were rearranged to
      create space where new actin structures formed. Disruption of microtubule
      prevented insulin-induced actin remodeling and distal insulin signal
      transduction, with reduction in surface glucose transporter isoform 4 (GLUT4) and
      glucose uptake. Though microtubule mediated actin remodeling through PKCzeta,
      reorganization of microtubule depended on tyrosine phosphorylation of insulin
      receptor, the mechanism is different from insulin-induced actin remodeling, which
      relied on the activity of PI3-kinase and PKCzeta. We propose that microtubule
      network is required for insulin-induced signal transduction and actin remodeling
      in skeletal muscle cells.

PMID- 22996140
TI  - Lipid solubility of warfarin may contribute to warfarin resistance in patients
      receiving total parenteral nutrition.

PMID- 22996139
TI  - The health education for lupus study:  a randomized controlled cognitive
      behavioral intervention targeting psychosocial adjustment and quality of life in
      adolescent females with systemic lupus erythematosus.
AB  - INTRODUCTION: To examine in a randomize controlled feasibility clinical trial the
      efficacy of a cognitive-behavioral intervention designed to manage pain, enhance
      disease adjustment and adaptation and improve quality of life among female
      adolescents with systemic lupus erythematosus. METHODS: Female adolescents (n =
      53) ranging in age from 12 to 18 years were randomly assigned to 1 of 3 groups
      including a cognitive-behavioral intervention, an education-only arm and a no
      contact control group. Participants were assessed at baseline, postintervention
      and at 3- and 6-month intervals after completion of the intervention. RESULTS: No
      significant differences were revealed among the 3 treatment arms for any of the
      dependent measures at any of the assessment points. For the mediator variables, a
      posthoc secondary analysis did reveal increases in coping skills from baseline to
      postintervention among the participants in the cognitive-behavioral intervention
      group compared with both the no-contact control group and the education-only
      group. CONCLUSION: Although no differences were detected in the primary outcome,
      a possible effect on coping of female adolescents with systemic lupus
      erythematosus was detected in this feasibility study. Whether the impact of
      training in the area of coping was of sufficient magnitude to generalize to other
      areas of functioning, such as adjustment and adaptation, is unclear. Future phase
      III randomized trials will be needed to assess additional coping models and to
      evaluate the dose of training and its influence on pain management, adjustment
      and health-related quality of life.

PMID- 22996142
TI  - Zirconium catalyzed alkyne dimerization for selective Z-enyne synthesis.
AB  - The regioselective head-to-head dimerization of alkynes is catalyzed by a
      dibenzyl tethered bis(ureate) zirconium precatalyst with aniline as an additive.
      This system also gives outstanding stereoselectivity to furnish Z-enynes in high
      yields. A dinuclear reactive intermediate has been characterized, which provides
      a potential mechanistic rationale for the unexpected regio- and stereoselectivity
      in this catalytic system.

PMID- 22996141
TI  - Performance status of patients is the major prognostic factor at all stages of
      pancreatic cancer.
AB  - BACKGROUND: The aim of this study was to identify and evaluate the
      clinicopathologic factors and to elucidate the clinical importance of performance
      status on the outcome of patients with pancreatic cancer. MATERIALS AND METHOD:
      The data of 335 patients with histologically confirmed diagnosis of pancreatic
      cancer who were treated and followed up between 2000 and 2010 were recorded from
      medical charts. RESULTS: The median age of the patients was 59 years (range 25-88
      years) and 226 (67.5%) were male. The study group comprised localized disease
      (18%), locally advanced disease (36%) and metastatic disease (46%). The median
      survival of all patients was 280 days and the 4-year survival rate was 5%.
      Univariate analysis indicated that initial poor performance status of patients
      (PS 2-4) was significantly associated with shorter survival in localized (p =
      0.015), locally advanced (p = 0.01), metastatic stage (p < 0.001) and in the
      whole group (p < 0.001). Multivariate analyses also showed the same findings
      except in local disease (p = 0.04 for locally advanced disease, p = 0.002 for
      metastatic stage, and p < 0.001 for all stages). In patients with poor
      performance status, severe weight loss (>10%) (p = 0.007), large tumor diameter
      (>3 cm) (p = 0.046), and especially metastatic disease (p < 0.001) were
      associated with significantly shorter overall survival. CONCLUSIONS: The
      performance status of a patient is the major prognostic factor predicting overall
      survival for all stages of pancreatic cancer. Severe weight loss, large tumor,
      and metastatic disease were found to be unfavorable prognostic factors in
      patients with poor performance status.

PMID- 22996143
TI  - Laparoscopic radiofrequency ablation for the management of colorectal liver
      metastases: 10-year experience.
AB  - BACKGROUND: Published results addressing the treatment of colorectal liver
      metastases (CRLM) with radiofrequency ablation (RFA) vary widely with local
      recurrence rates of 2-40% and 5-year survival of 14-55%. The goal of this study
      was to analyze our 10-year experience with laparoscopic RFA. METHODS: From
      January 2000 to July 2010, 130 patients underwent laparoscopic RFA for CRLM.
      Kaplan-Meier analysis was used to assess survival. Univariate and multivariate
      analysis were performed to identify factors associated with survival and
      recurrence. RESULTS: In this cohort, median survival was 40.4 months with 5-year
      survival of 28.8%. Overall, 9.2% of patients had a local recurrence (3.6% for
      tumors 3 cm or less). On univariate analysis, factors associated with decreased
      survival were BMI (P = 0.045), rectal primary (P = 0.005), and increased tumor
      size (P = 0.002). On multivariate analysis, increased tumor size (HR 1.29 [95%
      CI: 1.04-1.59]; P = 0.020) and bilobar disease (HR 2.06 [95% CI: 1.02-4.15]; P =
      0.044) were associated with decreased survival. On univariate analysis, only BMI
      was found to be associated with disease recurrence (P = 0.025). CONCLUSIONS: Our
      data demonstrate that laparoscopic RFA can achieve a median survival of 40.4
      months with a low local recurrence rate. Patients with tumors 3 cm or less have a
      decreased risk of local recurrence.

PMID- 22996144
TI  - Continuous glucose monitoring after islet transplantation in type 1 diabetes: an
      excellent graft function (beta-score greater than 7) Is required to abrogate
      hyperglycemia, whereas a minimal function is necessary to suppress severe
      hypoglycemia (beta-score greater than 3).
AB  - CONTEXT: For the last 10 yr, continuous glucose monitoring (CGM) has brought up
      new insights into the accuracy of blood glucose analysis. OBJECTIVE: Our
      objective was to determine how islet graft function was able to influence the
      various components of dysglycemia after islet transplantation (IT). DESIGN AND
      SETTING: We conducted a single-arm open-labeled study with a 3-yr follow-up in a
      referral center (ClinicalTrial.gov identifiers NCT00446264 and NCT01123187).
      PATIENTS: Twenty-three consecutive patients with type 1 diabetes (14 islet alone,
      nine islet after kidney) received IT within 3 months using the Edmonton protocol.
      INTERVENTION: INTERVENTION included 72-h CGM before and 3, 6, 9, 12, 24, and 36
      months after transplantation. MAIN OUTCOME MEASURE: Graft function was estimated
      via beta-score, a previously validated index (range 0-8) based on treatment
      requirements, C-peptide, blood glucose, and glycated hemoglobin. RESULTS: At the
      3-yr visit, graft function persisted in 19 patients (82%), and 10 (43%) remained
      insulin independent. Glycated hemoglobin decreased in the whole cohort from 8.3%
      (7.3-9.0%) at baseline to 6.7% (5.9-7.7%) at 3 yr [median (interquartile range),
      P < 0.01]. Mean glucose, glucose sd, and time spent with glycemia above 10
      mmol/liter (hyperglycemia) and below 3 mmol/liter (hypoglycemia) were
      significantly lower after IT (P < 0.05 vs. baseline). The four CGM outcomes were
      related to beta-score (P < 0.001). However, partial function (beta-score >3) was
      sufficient to abrogate hypoglycemia; suboptimal function (beta-score >5) was
      necessary to significantly improve mean glucose, glucose sd, and hyperglycemia;
      and optimal function (beta score >7) was necessary to normalize them. CONCLUSION:
      The four components of dysglycemia were not equally affected by the degree of
      islet graft function, which could have important implications for future
      development of beta-cell replacement. A beta-score above 3 dramatically reduced
      the occurrence of hypoglycemia.

PMID- 22996146
TI  - Phosphodiesterase 11A (PDE11A) gene defects in patients with acth-independent
      macronodular adrenal hyperplasia (AIMAH): functional variants may contribute to
      genetic susceptibility of bilateral adrenal tumors.
AB  - CONTEXT: Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular
      cAMP levels. PDE11A function has been linked to predisposition to adrenocortical
      tumors. OBJECTIVE: The aim of the study was to study the PDE11A gene in a large
      cohort of patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH)
      and in control subjects. DESIGN: The PDE11A entire coding region was sequenced in
      46 patients with AIMAH and 192 controls. Two variants found in AIMAH patients
      were transiently expressed in HEK 293 and adrenocortical H295R cells for further
      functional studies. RESULTS: The frequency of all PDE11A variants was
      significantly higher among patients with AIMAH (28%) compared to controls (7.2%)
      (P = 5 * 10(-5)). Transfection of the two PDE11A variants found in AIMAH patients
      only (D609N or M878V) showed that cAMP levels were higher, after forskolin
      stimulation, in cells transfected with the PDE11A mutants, compared to cells
      transfected with the wild-type PDE11A in HEK 293 cells (P < 0.05). Moreover,
      transfection with mutants PDE11A increased transcriptional activity of a cAMP
      response element reporter construct compared to wild-type PDE11A in HEK 293 cells
      (P < 0.0004 for D609N and P < 0.003 for M878V) and in the adrenocortical H295R
      cells (P < 0.05 for D609N and M878V). In addition, analysis of cAMP levels in
      intact living culture cells by fluorescence resonance energy transfer probes
      showed increased cAMP in forskolin-treated cells transfected with PDE11A variants
      compared with wild-type PDE11A (P < 0.05). CONCLUSION: We conclude that PDE11A
      genetic variants may increase predisposition to AIMAH.

PMID- 22996149
TI  - Joseph B. Kirsner, MD, PhD, 1909-2012.

PMID- 22996148
TI  - Gender-specific alterations in fibrin structure function in type 2 diabetes:
      associations with cardiometabolic and vascular markers.
AB  - CONTEXT: Diabetes is associated with increased incidence of atherothrombotic
      disease. The fibrin network forms the backbone of the arterial thrombus, and
      fibrin clot structure determines predisposition to cardiovascular events.
      OBJECTIVES: The aim of the study was to investigate fibrin clot
      structure/fibrinolysis in the largest type 2 diabetes cohort and analyze
      associations with cardiometabolic risk factors and vascular pathology. DESIGN:
      Clot structure/fibrinolysis was assessed in 875 participants of the Edinburgh
      Type 2 Diabetes Study [age, 68 (range, 60-75) yr; 450 males] by turbidimetric
      assays, and clots were visualized by confocal microscopy. Four parameters of clot
      structure/fibrinolysis were analyzed, and plasma levels of fibrinogen and
      plasminogen activator inhibitor-1 were studied by Clauss assay and ELISA,
      respectively. RESULTS: Clot maximum absorbance was increased in females compared
      with males (0.37 +/- 0.005 and 0.34 +/- 0.005 arbitrary unit, respectively; P <
      0.001), and took longer to lyse (803 +/- 20 and 665 +/- 12 sec, respectively; P <
      0.001). These gender differences in clot structure and fibrinolysis were still
      evident after correcting for fibrinogen and plasminogen activator inhibitor-1
      plasma levels. A prothrombotic fibrin structure profile was associated with
      increased body mass index and low levels of high-density lipoprotein in women and
      with inadequate diabetes control in men. Clot formation time was related to
      previous cardiac ischemic events in both men and women after adjusting for
      traditional risk factors [odds ratio, 1.22 (95% confidence interval, 1.07, 1.38);
      and 1.33 (1.15, 1.50), respectively], and prothrombotic clots were associated
      with low ankle brachial index, renal impairment, and smoking, regardless of
      gender. CONCLUSIONS: Women with type 2 diabetes have compact clots with
      compromised fibrinolysis compared with men. There are gender-specific
      associations between clotting parameters and cardiometabolic risk factors in this
      population, whereas vascular abnormalities, impaired renal function, and smoking
      are associated with prothrombotic clot structure profile regardless of gender.

PMID- 22996147
TI  - Implications of sleep restriction and recovery on metabolic outcomes.
AB  - CONTEXT: Alongside the growing epidemics of obesity and diabetes mellitus,
      chronic partial sleep restriction is also increasingly common in modern society,
      and the metabolic implications of this have not been fully illustrated as yet.
      Whether recovery sleep is sufficient to offset these detriments is an area of
      ongoing research. OBJECTIVE: This review seeks to summarize the relevant
      epidemiological and experimental data in the areas of altered metabolic
      consequences of both shortened sleep and subsequent recovery sleep. DATA
      ACQUISITION: The medical literature from 1970 to March 2012 was reviewed for key
      articles. DATA SYNTHESIS: Epidemiological studies suggest associations between
      shortened sleep and future obesity and diabetes. Experimental data thus far show
      a probable link between shortened sleep and altered glucose metabolism as well as
      appetite dysregulation. CONCLUSION: Sleep often seems undervalued in modern
      society, but this may have widespread metabolic consequences as described in this
      review. Acute sleep loss is often unavoidable, but chronic sleep restriction
      ideally should not be. Understanding the implications of both sleep restriction
      and recovery on metabolic outcomes will guide public health policy and allow
      clinical recommendations to be prescribed.

PMID- 22996150
TI  - Highly selective Barbier-type propargylations and allenylations catalyzed by
      titanocene(III).
AB  - The alkyne functional group is found in many bioactive natural products and is
      the key to many important chemical transformations developed over recent years.
      Moreover, allenes have recently gained relevance as versatile reagents in organic
      synthesis. Mild, catalytic methods to enable the selective introduction of either
      alkyne or allene motifs into organic molecules are very valuable but, as yet,
      quite scarce. We describe an extremely mild and selective method for either the
      propargylation or allenylation of carbonyl compounds catalyzed by the abundant,
      safe, and inexpensive metal titanium. These reactions can selectively provide
      homopropargylic alcohols from aldehydes and ketones or alpha-hydroxy-allenes from
      aldehydes. The mechanisms involved were also investigated.

PMID- 22996151
TI  - A fast parallel clustering algorithm for molecular simulation trajectories.
AB  - We implemented a GPU-powered parallel k-centers algorithm to perform clustering
      on the conformations of molecular dynamics (MD) simulations. The algorithm is up
      to two orders of magnitude faster than the CPU implementation. We tested our
      algorithm on four protein MD simulation datasets ranging from the small Alanine
      Dipeptide to a 370-residue Maltose Binding Protein (MBP). It is capable of
      grouping 250,000 conformations of the MBP into 4000 clusters within 40 seconds.
      To achieve this, we effectively parallelized the code on the GPU and utilize the
      triangle inequality of metric spaces. Furthermore, the algorithm's running time
      is linear with respect to the number of cluster centers. In addition, we found
      the triangle inequality to be less effective in higher dimensions and provide a
      mathematical rationale. Finally, using Alanine Dipeptide as an example, we show a
      strong correlation between cluster populations resulting from the k-centers
      algorithm and the underlying density. (c) 2012 Wiley Periodicals, Inc.

PMID- 22996153
TI  - Light-triggered self-assembly of triarylamine-based nanospheres.
AB  - Tailored triarylamine units modified with terpyridine ligands were coordinated to
      Zn(2+) ions and characterized as discrete dimeric entities. Interestingly, when
      these complexes were subsequently irradiated with simple visible light in
      chloroform, they readily self-assembled into monodisperse spheres with a mean
      diameter of 160 nm.

PMID- 22996152
TI  - Just noticeable difference in perception of physical exertion during cycle
      exercise in young adult men and women.
AB  - The purpose of this investigation was to describe the just noticeable difference
      (JND) in perceived exertion during cycle exercise. Males (n = 20) and females (n
      = 26) (21.4 +/- 3.1 year) performed load-incremented cycle exercise to peak
      intensity. At the end of each minute, subjects rated their overall-body perceived
      exertion using the OMNI (0-10) rating of perceived exertion (RPE) scale.
      Individual regression derived the power output (PO) corresponding to RPE 5. This
      PO served as the standard stimulus (SS). On a separate occasion, four 5-min
      cycling bouts were performed with 5 min rest between bouts. During bouts 1 and 3
      subjects cycled at the SS. During bouts 2 and 4 subjects adjusted the resistance
      to achieve a level of exertion just noticeably above/below the SS. The difference
      in final 30-s oxygen consumption (VO2) and PO between each JND bout and the
      previous SS were the above (JND-A) and below (JND-B) perceived exertion JNDs. JND
      A and JND-B were compared between genders and between subjects exhibiting lower
      versus higher ventilatory threshold (VT) and VO(2PEAK) within genders for VO2 (l
      . min(-1), %VO(2PEAK)) and PO (W, %SS). JND-B was significantly (P < 0.05)
      greater than JND-A for VO2 and PO, when expressed in absolute (l . min(-1), W)
      and relative units (%VO(2PEAK), %SS). Males exhibited greater JND values than
      females in absolute, but not relative, units. Subjects with lower and higher VT
      and VO(2)PEAK exhibited similar JND values. The JND can serve as an effective
      tool to measure perceptual acuity and to determine individual ability to self
      regulate prescribed exercise intensities.

PMID- 22996145
TI  - The T1D Exchange clinic registry.
AB  - CONTEXT: The T1D Exchange includes a clinic-based registry, a patient-centric web
      site called Glu, and a biobank. OBJECTIVE: The aim of the study was to describe
      the T1D Exchange clinic registry and provide an overview of participant
      characteristics. DESIGN: Data obtained through participant completion of a
      questionnaire and chart extraction include diabetes history, management, and
      monitoring; general health; lifestyle; family history; socioeconomic factors;
      medications; acute and chronic diabetic complications; other medical conditions;
      and laboratory results. SETTING: Data were collected from 67 endocrinology
      centers throughout the United States. PATIENTS: We studied 25,833 adults and
      children with presumed autoimmune type 1 diabetes (T1D). RESULTS: Participants
      ranged in age from less than 1 to 93 yr, 50% were female, 82% were Caucasian, 50%
      used an insulin pump, 6% used continuous glucose monitoring, and 16% had a first
      degree family member with T1D. Glycosylated hemoglobin at enrollment averaged
      8.3% and was highest in 13 to 25 yr olds. The prevalence of renal disease was
      <=4% until T1D was present for at least 10 yr, and retinopathy treatment was <=2%
      until T1D was present for at least 20 yr. A severe hypoglycemic event (seizure or
      coma) in the prior 12 months was reported by 7% of participants and diabetic
      ketoacidosis in the prior 12 months by 8%. CONCLUSIONS: The T1D Exchange clinic
      registry provides a database of important information on individuals with T1D in
      the United States. The rich dataset of the registry provides an opportunity to
      address numerous issues of relevance to clinicians and patients, including
      assessments of associations between patient characteristics and diabetes
      management factors with outcomes.

PMID- 22996154
TI  - Time-of-flight neutron rejection to improve prompt gamma imaging for proton range
      verification: a simulation study.
AB  - Therapeutic proton and heavier ion beams generate prompt gamma photons that may
      escape from the patient. In principle, this allows for real-time, in situ
      monitoring of the treatment delivery, in particular, the hadron range within the
      patient, by imaging the emitted prompt gamma rays. Unfortunately, the neutrons
      simultaneously created with the prompt photons create a background that may
      obscure the prompt gamma signal. To enhance the accuracy of proton dose
      verification by prompt gamma imaging, we therefore propose a time-of-flight (TOF)
      technique to reject this neutron background, involving a shifting time window to
      account for the propagation of the protons through the patient. Time-resolved
      Monte Carlo simulations of the generation and transport of prompt gamma photons
      and neutrons upon irradiation of a PMMA phantom with 100, 150 and 200 MeV protons
      were performed using Geant4 (version 9.2.p02) and MCNPX (version 2.7.D). The
      influence of angular collimation and TOF selection on the prompt gamma and
      neutron longitudinal profiles is studied. Furthermore, the implications of the
      proton beam microstructure (characterized by the proton bunch width and
      repetition period) are investigated. The application of a shifting TOF window
      having a width of DeltaTOF(z) = 1.0 ns appears to reduce the neutron background
      by more than 99%. Subsequent application of an energy threshold does not appear
      to sharpen the distal falloff of the prompt gamma profile but reduces the tail
      that is observed beyond the proton range. Investigations of the influence of the
      beam time structure show that TOF rejection of the neutron background is expected
      to be effective for typical therapeutic proton cyclotrons.

PMID- 22996156
TI  - Influence of an intraoperative perilymph gusher on cochlear implant performance
      in children with labyrinthine malformations.
AB  - OBJECTIVES: To assess the effect of an intraoperative perilymph fluid gusher
      during cochlear implantation on speech perception abilities in pediatric patients
      with labyrinthine anomalies. SETTING: Tertiary care academic referral center.
      METHODS: Seventy subjects with labyrinthine malformations who received a cochlear
      implant were identified in our pediatric cochlear implant database. In 30 cases,
      an intraoperative perilymph fluid gusher was encountered during surgery. Fifteen
      children with GJB2 positive hereditary hearing loss served as controls. Multiple
      speech perception measures were obtained with the cochlear implant. The best
      score for each subject over time was determined as a speech reception index in
      quiet. This index was compared among groups and malformation types. RESULTS: The
      speech reception index in quiet demonstrated overall good performance scores of
      cochlear implantation in children with incomplete partitioning/enlarged
      vestibular aqueduct type malformations. Children with hypoplastic malformations,
      on the other hand, showed variable outcomes with many children demonstrating only
      limited long-term speech discrimination abilities. The presence or absence of a
      perilymph gusher did not significantly influence results after cochlear
      implantation. CONCLUSION: This report documents the variable outcomes of
      pediatric cochlear implantation in children with inner ear malformations. More
      importantly, anatomic parameters, such as the classification of the anomaly and
      the presence of a viable cochlear nerve, seem to influence performance measures
      substantially. The presence of a perilymph gusher did not influence outcomes in
      both hypoplastic and incomplete partitioning/enlarged vestibular aqueduct type
      malformations. LEVEL OF EVIDENCE: 2b Individual retrospective cohort study.

PMID- 22996155
TI  - Etiological contributions to the covariation between children's perceptions of
      inter-parental conflict and child behavioral problems.
AB  - Prior work has suggested that inter-parental conflict likely plays an etiological
      role in child behavior problems. However, family-level measurement of inter
      parental conflict in most traditional child twin studies has made it difficult to
      tease apart the specific causal mechanisms underlying this association. The
      Children's Perception of Inter-parental Conflict scale (CPIC) provides a child
      specific measurement tool for examining these questions, as its subscales tap
      multiple dimensions of conflict assessed from the child's (rather than the
      parent's) perspective. The current study examined (1) the degree of genetic and
      environmental influence on each of the CPIC subscales, and (2) etiological
      contributions to the covariation between the CPIC scales and parental reports of
      child behavioral problems. The CPIC was completed by 1,200 child twins (aged 6-11
      years) from the Michigan State University Twin Registry (MSUTR). Parents
      completed the Child Behavior Checklist (CBCL) to assess child internalizing and
      externalizing behavior problems. Multivariate models were examined to evaluate
      the relative contributions of genetic and environmental factors to both the CPIC
      scales and to their overlap with child behavioral outcomes. Modeling results
      indicated no significant moderation of sex or age. Significant environmental
      overlap emerged between the CPIC conflict properties scale and child
      internalizing and externalizing problems. By contrast, significant genetic
      correlations emerged between the CPIC self-blame scale and externalizing problems
      as well as between the CPIC threat scale and internalizing problems. Overall,
      findings suggest that the subscales of the CPIC are somewhat etiologically
      diverse and may provide a useful tool for future investigations of possible gene
      environment interplay.

PMID- 22996157
TI  - Distribution of glucocorticoid receptors and 11beta-hydroxysteroid dehydrogenase
      isoforms in the human inner ear.
AB  - HYPOTHESIS: Glucocorticoids (GCs) are widely used as a therapeutic modality for
      the inner ear disorders including Meniere's disease (MD). The concentration of
      GCs in the target cells is known to be regulated by 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD), an enzyme complex responsible for the conversion of
      hormonally active cortisol into inactive cortisone. There is no morphologic
      indication of glucocorticoid receptors (GRs) and 11beta-HSD isoforms (11beta-HSD1
      and 2) in human inner ear. OBJECTIVES: The objectives of this study are to
      determine whether GRs and the isoforms of 11beta-HSD are present in human inner
      ear tissues and to reveal their precise distribution. STUDY DESIGN: This study
      investigated the expression of GRs and 11beta-HSD isoforms (11beta-HSD1 and 2) in
      the human inner ear. METHODS: In humans, immunostaining of GRs, 11beta-HSD1, and
      11beta-HSD2 was performed in the stria vascularis (SV) and the vestibular
      tissues, whereas in the cochlear tissues except for the SV, only GRs were
      investigated. RESULTS: Immunoreactivity of GRs was detected in the SV, outer hair
      cells, inner hair cell, spiral ligament, Reissner's membrane, vestibular hair
      cells, vestibular nerve, transitional cells, and dark cells of the crista
      ampullaris. 11beta-HSD1 was observed in the SV, the apical area of the vestibular
      hair cells, the transitional cells, and the dark cells. However, no
      immunoreactivity of 11beta-HSD2 was observed. CONCLUSION: Those data indicate
      that different local steroid regulation by GRs and the isoforms of 11beta-HSD is
      present in various parts of the human inner ear tissues and that the tissues are
      a direct therapeutic target of glucocorticoids in the inner ear diseases.

PMID- 22996158
TI  - Mannitol protects hair cells against tumor necrosis factor alpha-induced loss.
AB  - HYPOTHESIS: Mannitol has otoprotective effects against tumor necrosis factor
      (TNF) alpha-induced auditory hair cell (HC) loss. BACKGROUND: Mannitol has been
      demonstrated to possess cytoprotective effects in several organ systems. Its
      protective effect on postischemic hearing loss has also been shown. Mannitol's
      otoprotective mechanism and site of action are at present unknown. MATERIALS AND
      METHODS: Organ of Corti (OC) explants were dissected from 3 day-old rat pups. The
      safety (nonototoxicity) of mannitol was assessed at 4 different concentrations (1
      100 mM). Three experimental arms were designed including: a control group,
      TNFalpha group, and TNFalpha + mannitol group. Cell viability was determined by
      counts of fluorescein isothiocyanate (FITC) phalloidin stained HC.
      Immunofluorescence assay of phospho-c-Jun and the proapoptotic mediators, cleaved
      caspase-3, apoptosis inducing factor (AIF), and endonuclease G (Endo G) were
      performed. RESULTS: Analysis of HC density confirmed the safety of mannitol at
      concentration ranges of 1 to 100 mM. The ototoxic effect of TNFalpha was
      demonstrated (p < 0.05). The otoprotective effect of 100 mM mannitol in TNFalpha
      challenged OC explants was also demonstrated (p < 0.001). Mannitol treatment
      reduced the high levels of phospho-c-Jun observed in the TNFalpha-challenged
      group. AIF cluster formation and EndoG translocation into the nuclei of HCs were
      also reduced by mannitol treatment. CONCLUSION: Mannitol significantly reduces
      the ototoxic effects of TNFalpha against auditory HC's potentially by inhibiting
      c-Jun N terminal kinase (JNK) activation pathway and AIF, EndoG nuclear
      translocation. This local otoprotective effect may have therapeutic implications
      in inner ear surgery, for example, cochlear implants, protection of residual
      hearing, as well as implications for postischemic inner ear insults.

PMID- 22996160
TI  - Otopathology in Osteogenesis Imperfecta.
AB  - BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic disorder of connective
      tissue matrix. OI is caused by mutations that affect type I collagen. The hearing
      loss in OI is characterized by onset in early adulthood and can be conductive,
      sensorineural, or mixed. OBJECTIVES: To describe the temporal bone histopathology
      in 9 individuals with OI. MATERIALS AND METHODS: Four adult, 1 pediatric, and 4
      infant specimens were identified. Temporal bones were removed at autopsy and
      studied using light microscopy. RESULTS: All adults and 1 pediatric specimen
      showed otosclerotic lesions. The findings included examples of clinical,
      histologic, and cochlear otosclerosis. The temporal bones of infants showed
      delayed ossification of the endochondral layer of bone and of the ossicles. There
      were no infant specimens with otosclerotic lesions. CONCLUSION: Hearing loss in
      OI may be the result of clinical or cochlear otosclerosis. Fracture or atrophy of
      the ossicles may also be present in OI. A third unidentified mechanism of hearing
      loss may lead to cochlear degeneration. The described findings of otosclerotic
      lesions have implications for the observed heterogeneity of hearing loss patterns
      and for the surgical management of hearing loss in OI.

PMID- 22996161
TI  - Sudden onset hearing loss and vertigo just before posterior inferior cerebellar
      artery infarction (lateral medulla syndrome).

PMID- 22996162
TI  - Sex and age associations with vestibular schwannoma size and presenting symptoms.
AB  - OBJECTIVE: To assess the association of sex and age with presenting symptoms and
      size of vestibular schwannoma at clinical presentation to our clinics. STUDY
      DESIGN: Retrospective chart review. SETTING: Academic medical center. PATIENTS:
      Approximately 1,269 subjects diagnosed with unilateral vestibular schwannoma
      between 1997 and 2010. INTERVENTION: Demographic information, tumor
      characteristics, and treatment strategy were recorded. MAIN OUTCOME MEASURE:
      Tumor size, patient-reported presence of hearing loss or dizziness at
      presentation. RESULTS: Male subjects had significantly larger tumors than female
      subjects at presentation (18.23 versus 16.81 mm, p = 0.031); this difference was
      particularly pronounced in patients younger than 40 years. Patient-reported
      symptoms at baseline also differed by sex: the prevalence of hearing loss was
      95.1% in male subjects versus 90.3% in female subjects (p = 0.001), and the
      frequency of dizziness was 74.3% in female subjects versus 59.0% in male subjects
      (p<0.0001). In multivariate analyses, male subjects continued to have a
      borderline significant positive association with tumor size (p = 0.066) and were
      2-fold more likely to have hearing loss (odds ratio [OR], 2.082; 95% confidence
      interval [CI], 1.300-3.336) but half as likely to have dizziness (OR, 0.501; 95%
      CI, 0.387-0.649) than female subjects. Additionally, for every 1-mm increase in
      tumor size, patients were more likely to report hearing loss by 14.7% (OR, 1.147;
      95% CI, 1.106-1.191) and dizziness by 2.8% (OR, 1.028; 95% CI, 1.016-1.041).
      CONCLUSION: We observed significant sex differences in the presentation and size
      of unilateral vestibular schwannomas. As management and treatment strategies are
      predicated on presenting symptoms and patient factors, these observations merit
      further study to further understand tumor biology, improve risk stratification,
      and optimize tumor management.

PMID- 22996163
TI  - Evaluation of masking effects on speech perception in patients with unilateral
      chronic tinnitus using the hearing in noise test.
AB  - OBJECTIVE: To verify that tinnitus itself could disturb speech perception and to
      evaluate the effects of masking noise on speech perception ability in the
      patients with normal hearing but unilateral chronic tinnitus using the hearing in
      noise test. STUDY DESIGN: Prospective, nonrandomized study. MATERIALS AND
      METHODS: Between June 2009 and May 2011, we enrolled 20 patients with normal
      hearing and subjective unilateral tinnitus that had persisted for more than 12
      months, along with 20 healthy controls of the same age. All subjects were
      evaluated using audiologic examinations, the tinnitus handicap inventory, and the
      Korean version of the Hearing in Noise Test (K-HINT) to assess characteristics of
      tinnitus and speech perception ability in various noisy situations. RESULTS:
      Reception threshold for speech (RTS) in a quiet environment and signal-to-noise
      ratio (SNR) in various conditions of noise were significantly higher in the
      tinnitus than in the control group, regardless of whether noise came from the
      front, right, or left (p < 0.05). When the tinnitus group was subdivided
      according to the site of noise exposure, the mean SNR of the contralateral noise
      group was -7.9 +/- 1.4 dB, which was significantly higher than the ipsilateral
      noise (-9.1 +/- 1.8 dB) or control group (right, -10.0 +/- 0.6 dB; left, -10.1 +/
      0.5 dB) (p < 0.05). In addition, there was no significant difference between
      ipsilateral noise and control groups. CONCLUSION: From this study, we showed that
      tinnitus itself could adversely affect speech perception ability by increasing
      both RTS and SNR in the tinnitus patients in comparison with healthy controls. In
      addition, we suggest that proper level of noise on the site of tinnitus might be
      helpful to increase speech perception in the patients who experience chronic
      subjective tinnitus.

PMID- 22996164
TI  - Langerhans cells in the human tympanic membrane in health and disease:  a
      morphometric analysis.
AB  - HYPOTHESIS: The normal tympanic membrane contains Langerhans dendritic cells, and
      they play a role in the pathogenesis of chronic suppurative otitis media.
      BACKGROUND: The presence of Langerhans dendritic cells in the normal tympanic
      membrane is disputed. However, they have been identified in tympanic membranes of
      patients with otitis media. A quantitative analysis of the distribution and
      morphology of these cells in the types of chronic suppurative otitis media has
      not been undertaken. METHODS: Samples of normal cadaveric tympanic membranes and
      those from patients with chronic suppurative otitis media of the tubotympanic and
      atticoantral varieties were stained with the immunohistochemical marker CD1a. The
      number of cells per unit length of basement membrane, diameters of cells, and
      number and length of dendritic processes were compared between the groups.
      RESULTS: CD1a-positive Langerhans dendritic cells were present in the normal
      tympanic membrane. The number of cells per unit length of basement membrane,
      diameters of cells, and the length of dendritic processes increased significantly
      in tubotympanic disease and in atticoantral disease, the difference being more
      pronounced in the latter form of otitis media. CONCLUSION: Langerhans cells are
      present in the normal tympanic membrane, and they probably play differing roles
      in the pathogenesis of tubotympanic and atticoantral forms of chronic suppurative
      otitis media.

PMID- 22996165
TI  - Microsurgery versus stereotactic radiation for small vestibular schwannomas: a
      meta-analysis of patients with more than 5 years' follow-up.
AB  - OBJECTIVE: To compare the long-term outcome of hearing and tumor outcome of small
      vestibular schwannomas treated with stereotactic radiation and microsurgery. DATA
      SOURCES: A thorough search for English-language publications and "in process"
      articles dating from 1948 to December 2011 was conducted using Ovid MEDLINE.
      STUDY SELECTION: The principal criteria were patients having had microsurgery or
      radiation therapy as their sole treatment, with a follow-up of at least 5 years,
      and a useful hearing level at diagnosis. DATA EXTRACTION: Sixteen studies met our
      criteria. Hearing preservation outcome (worse or preserved) and tumor outcome
      (failure, control) data, as well as all other significant observations, were
      collected from the articles. Stereotactic radiation was the only radiation
      therapy analyzed. DATA SYNTHESIS: The Pearson chi test was our primary
      statistical analysis. CONCLUSION: Stereotactic radiation showed significantly
      better long-term hearing preservation outcome rates than microsurgery (p <
      0.001). However, long-term tumor outcome was not significantly different in
      stereotactic radiation as compared with microsurgery (p = 0.122). Although
      stereotactic radiation demonstrates a more favorable long-term hearing
      preservation outcome as compared with microsurgery, additional studies are
      required to provide the medical field with a better understanding of vestibular
      schwannoma treatment.

PMID- 22996166
TI  - Statistical considerations are necessary in assessing associations between
      micronutrient intake and times to clinical events.

PMID- 22996167
TI  - Retraction.

PMID- 22996170
TI  - Psychopathic traits in females and males across the globe.
AB  - The current study examined the prevalence and structure of psychopathic traits in
      females and males using a very large world sample (N = 33,016, females = 19,183).
      Psychopathic traits were assessed with the Self-Report Psychopathy (SRP) scale,
      and structural equation modeling (SEM) was used to test the four-factor model of
      psychopathy (interpersonal, affective, lifestyle, antisocial) both in the total
      sample and in the separate samples of females and males. Multi-sample
      confirmatory factor analysis was used to test for invariance of model parameters
      across sex as well as across females from different world regions. Inferential
      statistics were used to examine how the mean-level average of the four SRP facets
      varied as a function of culture and sex. Finally, the SRP data were linked to
      objective world health data (e.g., mortality, fertility, gross domestic product)
      from relevant world regions. The results indicated good support for the four
      factor model, as well as invariance across sex and reasonably good evidence of
      invariance across females from different world regions. Variation in the
      elevation of SRP facet scores across major world regions suggested that cultural
      factors moderated the expression of the level of psychopathic propensities and
      that these traits were strongly correlated with the world health data.

PMID- 22996169
TI  - A Bayesian model for misclassified binary outcomes and correlated survival data
      with applications to breast cancer.
AB  - Breast cancer patients may experience ipsilateral breast tumor relapse (IBTR)
      after breast conservation therapy. IBTR is classified as either true local
      recurrence or new ipsilateral primary tumor. The correct classification of IBTR
      status has significant implications in therapeutic decision-making and patient
      management. However, the diagnostic tests to classify IBTR are imperfect and
      prone to misclassification. In addition, some observed survival data (e.g., time
      to relapse, time from relapse to death) are strongly correlated with IBTR status.
      We present a Bayesian approach to model the potentially misclassified IBTR status
      and the correlated survival information. We conduct the inference using a
      Bayesian framework via Markov chain Monte Carlo simulation implemented in
      WinBUGS. Extensive simulation shows that the proposed method corrects biases and
      provides more efficient estimates for the covariate effects on the probability of
      IBTR and the diagnostic test accuracy. Moreover, our method provides useful
      subject-specific patient prognostic information. Our method is motivated by, and
      applied to, a dataset of 397 breast cancer patients.

PMID- 22996172
TI  - Tailored nanostructuring of end-group-functionalized high-density polyethylene
      synthesized by an efficient catalytic version of Ziegler's "Aufbaureaktion".
AB  - Monoguanidinato titanium complexes are efficient catalysts to make OH end-group
      functionalized polyethylene (PE-OH) by a catalyzed version of Ziegler's
      "Aufbaureaktion". This PE-OH can be structured to mesoporous polyethylene or
      polyethylene nanofibers/ribbons through diblock copolymer synthesis, microphase
      separation, and etching of the sacrificial polylactide block.

PMID- 22996171
TI  - Interventions to improve retention in HIV primary care: a systematic review of
      U.S. studies.
AB  - Retaining HIV-diagnosed persons in care is a national priority, but little is
      known on what intervention strategies are most effective for promoting retention
      in care. We conducted a systematic search and qualitatively reviewed 13 published
      studies and three recent conference presentations to identify evidence-informed
      retention strategies. We extracted information on study design, methods, and
      intervention characteristics. Strengths-based case management that encourages
      clients to recognize and use their own internal abilities to access resources and
      solve problems offered strong evidence for retention in care. Other evidence
      informed strategies included peer navigation, reducing structural- and system
      level barriers, including peers as part of a health care team, displaying posters
      and brochures in waiting rooms, having medical providers present brief messages
      to patients, and having clinics stay in closer contact with patients across time.
      Opportunities for additional intervention strategies include using community
      based organizations as a setting for engaging HIV-infected persons about the
      importance of regular care and involving patients' significant others in
      retention in care interventions.

PMID- 22996173
TI  - The essential adaptors of innate immune signaling.
AB  - Microbial components and the endogenous molecules released from damaged cells can
      stimulate germ-line-encoded pattern recognition receptors (PRRs) to transduce
      signals to the hub of the innate immune signaling network-the adaptor proteins
      MyD88/TRIF/MAVS/STING/Caspase-1, where integrated signals relay to the relevant
      transcription factors IRF3/IRF7/NF-kappaB/ AP-1 and the signal transducer and
      activator of transcription 6 (STAT6) to trigger the expression of type I
      interferons and inflammatory cytokines or the assembly of inflammasomes. Most
      pleiotropic cytokines are secreted and bind to specific receptors, activating the
      signaling pathways including JAK-STAT for the proliferation, differentiation and
      functional capacity of immune cells. This review focuses on several critical
      adaptors in innate immune signaling cascades and recent progress in their
      molecular mechanisms.

PMID- 22996174
TI  - Direct lineage conversion: induced neuronal cells and induced neural stem cells.
AB  - Cellular reprogramming to neural cells is an area of ongoing study in
      developmental neuroscience, and recent research has generated remarkable
      achievements. Several studies have shown that the ectopic expression of specific
      neural transcription factors can convert terminally differentiated cells into
      neural cells. Here, we review the most recent progress in the field of induced
      neuronal (iN) cells and induced neural stem (iNS) cells and their potential
      clinical applications.

PMID- 22996176
TI  - Corneal confocal microscopy detects small-fiber neuropathy in Charcot-Marie-Tooth
      disease type 1A patients.
AB  - INTRODUCTION: Although unmyelinated nerve fibers are affected in Charcot-Marie
      Tooth type 1A (CMT1A) disease, they have not been studied in detail due to the
      invasive nature of the techniques needed to study them. We established
      alterations in C-fiber bundles of the cornea in patients with CMT1A using non
      invasive corneal confocal microscopy (CCM). METHODS: Twelve patients with CMT1A
      and 12 healthy control subjects underwent assessment of neuropathic symptoms and
      deficits, electrophysiology, quantitative sensory testing, corneal sensitivity,
      and corneal confocal microscopy. RESULTS: Corneal sensitivity, corneal nerve
      fiber density, corneal nerve branch density, corneal nerve fiber length, and
      corneal nerve fiber tortuosity were significantly reduced in CMT1A patients
      compared with controls. There was a significant correlation between corneal
      sensation and CCM parameters with the severity of painful neuropathic symptoms,
      cold and warm thresholds, and median nerve CMAP amplitude. CONCLUSIONS: CCM
      demonstrates significant damage to C-fiber bundles, which relates to some
      measures of neuropathy in CMT1A patients.

PMID- 22996177
TI  - Identification of the V600D mutation in Exon 15 of the BRAF oncogene in
      congenital, benign langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a well-known but rare disease that may
      occur at any age with markedly variable clinical features: self-regressive,
      localized, multiorgan, aggressive, or fatal outcome. Congenital LCH is rare and
      often clinically benign. While LCH is characterized by a clonal proliferation of
      Langerhans cells, its etiology is unknown. Although BRAF V600E mutations were
      recently identified as a recurrent genetic alteration in LCH cases, the clinical
      significance of this mutation within the heterogeneous spectrum of LCH is also
      currently unknown. We studied a cutaneous, benign form of congenital LCH that
      occurred in a newborn male, without recurrence for 8 years. Histopathologically,
      the skin lesion excised after birth showed the typical cytologic and
      immunophenotypic features of LCH. Sequencing analysis of Exon 15 of the BRAF gene
      revealed the V600D mutation, with an allelic abundance of 25-30%, corresponding
      to the LCH cells being hemizygous for the mutant allele. BRAF V600E-specific
      polymerase chain reaction was negative. Our report is the first to identify the
      rare, variant BRAF V600D mutation in LCH, and provides support for constitutively
      activated BRAF oncogene-induced cell senescence as a mechanism of regression in
      congenital, benign LCH. Further, our clinicopathologic findings provide proof for
      the first time that the V600D mutation can also occur in the absence of
      ultraviolet light, and can occur in a clinically benign proliferation, similar to
      the V600E mutation. Additional clinicopathologic studies in larger numbers of LCH
      patients may be valuable to ascertain the pathophysiologic role of BRAF mutations
      in LCH.

PMID- 22996175
TI  - The BK channel: a vital link between cellular calcium and electrical signaling.
AB  - Large-conductance Ca2+-activated K+ channels (BK channels) constitute an key
      physiological link between cellular Ca2+ signaling and electrical signaling at
      the plasma membrane. Thus these channels are critical to the control of action
      potential firing and neurotransmitter release in several types of neurons, as
      well as the dynamic control of smooth muscle tone in resistance arteries, airway,
      and bladder. Recent advances in our understanding of K+ channel structure and
      function have led to new insight toward the molecular mechanisms of opening and
      closing (gating) of these channels. Here we will focus on mechanisms of BK
      channel gating by Ca2+, transmembrane voltage, and auxiliary subunit proteins.

PMID- 22996178
TI  - Spontaneous electrical activity recorded from the aphid central nervous system.
AB  - Whilst many classes of insecticides target the insect central nervous system
      (CNS), their effects in the CNS of pest aphids have not been demonstrated. In
      this report, we describe an electrophysiological method for recording spontaneous
      neuronal activity from the giant willow aphid (Tuberolachnus salignus). Using
      extracellular recording electrodes and two analysis methods (threshold and
      template search), spontaneous spike activity was shown to exhibit sensitivity to
      the neuroexcitatory insecticide imidacloprid. This method allows changes in the
      frequency of action-potentials to be monitored during direct bath exposure to
      chemical agents, enabling a means of assessing and comparing neurotoxic effects
      of insecticides in a previously inaccessible superfamily of pest insects.

PMID- 22996179
TI  - Expression of MAC30 protein is related to survival and clinicopathological
      variables in breast cancer.
AB  - BACKGROUND AND OBJECTIVES: MAC30 is a protein with unknown function that is
      differentially expressed in certain malignancies. The aims of this study were to
      evaluate the relationship between MAC30 expression and clinicopathologic features
      while investigate the prognostic value of MAC30 expression in breast cancer.
      METHODS: Immunohistochemistry was used to examine MAC30 expression in 243 breast
      cancer tissues, meanwhile in 59 matched adjacent noncancerous tissues and 46
      benign breast tumor tissues as controls. The correlation of MAC30 expression with
      clinicopathological parameters was assessed using chi(2) analysis. The Kaplan
      Meier method and Cox proportional hazards model were used to predict factors with
      a significant independent prognostic value. RESULTS: MAC30 was overexpressed in
      breast cancer compared with matched adjacent noncancerous tissues and benign
      breast tumor (both P < 0.001). Moreover, MAC30 expression was correlated with
      tumor size, TNM stage, lymph node metastasis, and recurrence. Furthermore, it was
      shown that patients with high MAC30 expression had significantly poorer overall
      survival (OS) and disease-free survival (DFS; P = 0.002 and P = 0.007,
      respectively). Multivariate Cox regression analysis revealed that high MAC30
      expression was an independent prognostic factor for both OS and DFS (P = 0.018
      and P = 0.044, respectively). CONCLUSIONS: Overexpression of MAC30 was associated
      with tumor progression, recurrence, and poor survival in breast cancer. Testing
      expression of MAC30 will be helpful for predicting prognosis in breast cancer.

PMID- 22996180
TI  - PAI-1 and diabetes: a journey from the bench to the bedside.

PMID- 22996181
TI  - Insulin detemir in pregnancy: a small but significant step forward?

PMID- 22996184
TI  - Comment on: Inzucchi et al. Management of hyperglycemia in type 2 diabetes: a
      patient-centered approach. Position statement of the American Diabetes
      Association (ADA) and the European Association for the Study of Diabetes (EASD).
      Diabetes Care 2012;35:1364-1379.

PMID- 22996182
TI  - Individualizing targets and tactics for high-risk patients with type 2 diabetes:
      practical lessons from ACCORD and other cardiovascular trials.

PMID- 22996185
TI  - Comment on: Inzucchi et al. Management of hyperglycemia in type 2 diabetes: a
      patient-centered approach. Position statement of the American Diabetes
      Association (ADA) and the European Association for the Study of Diabetes (EASD).
      Diabetes Care 2012;35:1364-1379.

PMID- 22996187
TI  - Comment on: Rayner et al. Stomach bugs and diabetes: an astounding observation or
      just confounding? Diabetes Care 2012;35:463-464.

PMID- 22996188
TI  - Comment on: Alssema et al. One risk assessment tool for cardiovascular disease,
      type 2 diabetes, and chronic kidney disease. Diabetes Care 2012; 35:741-748.

PMID- 22996189
TI  - Hepatitis B virus polymerase impairs interferon-alpha-induced STA T activation
      through inhibition of importin-alpha5 and protein kinase C-delta.
AB  - Treatment with exogenous interferon (IFN)-alpha is not effective in the majority
      of patients with chronic hepatitis B virus (HBV) infection. Recent evidence
      suggests that HBV has evolved strategies to block the nuclear translocation of
      signal transducer and activator of transcription (STAT) 1 to limit IFN-alpha
      induced cellular antiviral responses. However, it remains unclear whether STAT1
      translocation is impaired in chronic hepatitis B patients and what mechanisms are
      involved. Here we report that the expression of HBV polymerase (Pol) in human
      hepatic cell lines inhibited induction of IFN-stimulated genes and resulted in a
      weakened antiviral activity of IFN-alpha. Ectopic expression of Pol suppressed
      IFN-alpha-induced STAT1 serine 727 phosphorylation and STAT1/2 nuclear
      accumulation, whereas STAT1 tyrosine 701 phosphorylation, and STAT1-STAT2
      heterodimer formation were not affected. Further studies demonstrated that Pol
      interacted with the catalytic domain of protein kinase C-delta (PKC-delta) and
      perturbed PKC-delta phosphorylation and its association with STAT1, which
      resulted in the suppression of STAT1 Ser727 phosphorylation. Moreover, Pol was
      found to interfere with nuclear transportation of STAT1/2 by competitively
      binding to the region of importin-alpha5 required for STAT1/2 recruitment.
      Truncation analysis suggested that the terminal protein and RNase H domains of
      Pol were able to bind to PKC-delta and importin-alpha5, respectively, and were
      responsible for the inhibition of IFN-alpha signaling. More importantly, the
      inhibition of STAT1 and PKC-delta phosphorylation were confirmed in a
      hydrodynamic-based HBV mouse model, and the blockage of IFN-alpha-induced STAT1/2
      nuclear translocation was observed in HBV-infected cells from liver biopsies of
      chronic HBV patients. CONCLUSIONS: These results demonstrate a role for Pol in
      HBV-mediated antagonization of IFN-alpha signaling and provide a possible
      molecular mechanism by which HBV resists the IFN therapy and maintains its
      persistence.

PMID- 22996190
TI  - The first catalytic synthesis of an acrylate from CO2 and an alkene-a rational
      approach.
AB  - For more than three decades the catalytic synthesis of acrylates from the cheap
      and abundantly available C(1) building block carbon dioxide and alkenes has been
      an unsolved problem in catalysis research, both in academia and industry. Herein,
      we describe a homogeneous catalyst based on nickel that permits the catalytic
      synthesis of the industrially highly relevant acrylate sodium acrylate from
      CO(2), ethylene, and a base, as demonstrated, at this stage, by a turnover number
      of greater than 10 with respect to the metal.

PMID- 22996191
TI  - Controlled synthesis of iron oxide nanoplates and nanoflowers.
AB  - An effective approach to synthesizing crystalline iron oxide nanoplates (~3 nm
      thick) and nanoflowers composed of ~5 nm small grains was reported. The formation
      of different-shaped nanoparticles in a similar system was achieved by controlling
      the nucleus concentration and growth rate.

PMID- 22996192
TI  - VEGF165 attenuates the Th17/Treg imbalance that exists when transplanting
      allogeneic skeletal myoblasts to treat acute myocardial infarction.
AB  - OBJECTIVES: To investigate whether Th17/Treg imbalance exists, and whether
      VEGF(165) attenuates the imbalance in allogeneic skeletal myoblast
      transplantation (allo-SMT) for acute myocardial infarction (AMI). METHODS: On
      days 1, 2, 4, and 7 after allo-SMT, the percentages and ratios of Th17 and Treg
      cells were analyzed by flow cytometry in three groups-the AMI group, the AMI-S
      group (allo-SMT) and the AMI-V group (with VEGF(165) treatment). Subsequently,
      related proinflammatory and regulatory cytokines and key transcription factors,
      ROR-gammat mRNA and Foxp3 mRNA expression, were examined by Bio-plex and real
      time polymerase chain reaction, respectively. RESULTS: On days 1, 2, 4, and 7,
      the percentage of Tregs, related cytokine concentrations and transcript factor
      Foxp3 mRNA in the AMI-S group were lower than those in the AMI group, while those
      in the AMI-V group were higher than those in the AMI group. However, the
      percentage of Th17 cells, related cytokine concentrations and ROR-gammat mRNA in
      the AMI-S group were higher than those in the AMI group; those in the AMI-V group
      were lower than those in the AMI group. Compared with the AMI group, the ratios
      of Th17/Treg cells significantly increased in the AMI-S group and decreased in
      the AMI-V group. CONCLUSIONS: Th17/Treg imbalance participated in the formation
      and development of the inflammatory and immune response after allo-SMT. However,
      transfected VEGF(165) was able to relieve the severity of the Th17/Treg
      imbalance.

PMID- 22996194
TI  - BaTiO3-based nanolayers and nanotubes: first-principles calculations.
AB  - The first-principles calculations using hybrid exchange-correlation functional
      and localized atomic basis set are performed for BaTiO(3) (BTO) nanolayers and
      nanotubes (NTs) with the structure optimization. Both the cubic and the
      ferroelectric BTO phases are used for the nanolayers and NTs modeling. It follows
      from the calculations that nanolayers of the different ferroelectric BTO phases
      have the practically identical surface energies and are more stable than
      nanolayers of the cubic phase. Thin nanosheets composed of three or more dense
      layers of (0 1 0) and (0 1 1[overline]) faces preserve the ferroelectric
      displacements inherent to the initial bulk phase. The structure and stability of
      BTO single-wall NTs depends on the original bulk crystal phase and a wall
      thickness. The majority of the considered NTs with the low formation and strain
      energies has the mirror plane perpendicular to the tube axis and therefore cannot
      exhibit ferroelectricity. The NTs folded from (0 1 1[overline]) layers may show
      antiferroelectric arrangement of Ti-O bonds. Comparison of stability of the BTO
      based and SrTiO(3)-based NTs shows that the former are more stable than the
      latter.

PMID- 22996193
TI  - Structure-function correlations of pulmonary surfactant protein SP-B and the
      saposin-like family of proteins.
AB  - Pulmonary surfactant is a lipid-protein complex secreted by the respiratory
      epithelium of mammalian lungs, which plays an essential role in stabilising the
      alveolar surface and so reducing the work of breathing. The surfactant protein SP
      B is part of this complex, and is strictly required for the assembly of pulmonary
      surfactant and its extracellular development to form stable surface-active films
      at the air-liquid alveolar interface, making the lack of SP-B incompatible with
      life. In spite of its physiological importance, a model for the structure and the
      mechanism of action of SP-B is still needed. The sequence of SP-B is homologous
      to that of the saposin-like family of proteins, which are membrane-interacting
      polypeptides with apparently diverging activities, from the co-lipase action of
      saposins to facilitate the degradation of sphingolipids in the lysosomes to the
      cytolytic actions of some antibiotic proteins, such as NK-lysin and granulysin or
      the amoebapore of Entamoeba histolytica. Numerous studies on the interactions of
      these proteins with membranes have still not explained how a similar sequence and
      a potentially related fold can sustain such apparently different activities. In
      the present review, we have summarised the most relevant features of the
      structure, lipid-protein and protein-protein interactions of SP-B and the saposin
      like family of proteins, as a basis to propose an integrated model and a common
      mechanistic framework of the apparent functional versatility of the saposin fold.

PMID- 22996195
TI  - A core set of metabolite sink/source ratios indicative for plant organ
      productivity in Lotus japonicus.
AB  - Plant growth is an important process in physiological as well as ecological
      respect and a number of metabolic parameters (elemental ratios as well as steady
      state levels of individual metabolites) have been demonstrated to reflect this
      process on the whole plant level. Since plant growth is highly localized and is
      the result of a complex interplay of metabolic activities in sink and source
      organs, we propose that ratios in metabolite levels of sink and source organs are
      particularly well suited to characterize this process. To demonstrate such a
      connection, we studied organ-specific metabolite ratios from Lotus japonicus
      treated with mineral nutrients, salt stress or arbuscular mycorrhizal fungi. The
      plants were displaying a wide range of biomass and of flower/biomass ratios. In
      the analysis of our data we looked for correlations between shifts in sink/source
      metabolite ratios and plant productivity (biomass accumulated at the time of
      harvest). In addition we correlated shifts in metabolite ratios comparing
      competing generative and vegetative sink organs with shifts in productivity of
      the two organs (changes in flower/biomass ratios). In our analyses we observed
      clear shifts of carbohydrates and of compounds connected to nitrogen metabolism
      in favour of sink organs of particularly high productivity. These shifts were in
      agreement with general differences in metabolite steady-state levels when
      comparing sink and source organs. Our findings suggest that differentiation of
      sink and source organs during sampling for metabolomic experiments substantially
      increases the amount of information obtained from such experiments.

PMID- 22996196
TI  - Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the
      mouse brain.
AB  - The development of effective strategies for gene therapy has been hampered by
      difficulties verifying transgene delivery in vivo and quantifying gene expression
      non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution
      and three-dimensional views, without tissue depth limitations. The iron-storage
      protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic
      ferrihydrite core that can be detected by MRI via its effect on the local
      magnetic field experienced by water protons. In an effort to better characterize
      the ferritin reporter for central nervous system applications, we expressed
      ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type
      1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates
      in the mouse brain with ascending doses of ferritin-expressing HSV-1. We
      established that the transverse relaxation rates correlate significantly to the
      number of inoculated infectious particles. Our results are potentially useful for
      quantitatively assessing limitations of ferritin reporters for gene therapy
      applications.

PMID- 22996197
TI  - Generation of an optimized lentiviral vector encoding a high-expression factor
      VIII transgene for gene therapy of hemophilia A.
AB  - We previously compared the expression of several human factor VIII (fVIII)
      transgene variants and demonstrated the superior expression properties of B
      domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule
      (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain
      the high-expression characteristics of porcine fVIII. The bioengineered construct
      then was used effectively to treat knockout mice with hemophilia A. In the
      current study, we focused on optimizing self-inactivating (SIN) lentiviral vector
      systems by analyzing the efficacy of various lentiviral components in terms of
      virus production, transduction efficiency and transgene expression. Specifically,
      three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional
      regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3)
      various internal promoters. The inclusion of a WPRE sequence had negligible
      effects on viral production and HP-fVIII expression. HIV and SIV vectors were
      compared and found to be similar with respect to transduction efficiency in both
      K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII
      by the SIV system, which was evident in both K562 and BHK-M cell lines. To
      further compare expression of HP-fVIII from an SIV-based lentiviral system, we
      constructed expression vectors containing the high expression transgene and a
      human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase
      promoter. Expression was significantly greater from the CMV promoter, which also
      yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these
      studies, an optimized vector contains the HP-fVIII transgene driven by a CMV
      internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

PMID- 22996198
TI  - Statistical analyses and computational prediction of helical kinks in membrane
      proteins.
AB  - We have carried out statistical analyses and computer simulations of helical
      kinks for TM helices in the PDBTM database. About 59 % of 1562 TM helices showed
      a significant kink, and 38 % of these kinks are associated with prolines in a
      range of +/-4 residues. Our analyses show that helical kinks are more populated
      in the central region of helices, particularly in the range of 1-3 residues away
      from the helix center. Among 1,053 helical kinks analyzed, 88 % of kinks are
      bends (change in helix axis without loss of helical character) and 12 % are
      disruptions (change in helix axis and loss of helical character). It is found
      that proline residues tend to cause larger kink angles in helical bends, while
      this effect is not observed in helical disruptions. A further analysis of these
      kinked helices suggests that a kinked helix usually has 1-2 broken backbone
      hydrogen bonds with the corresponding N-O distance in the range of 4.2-8.7 A,
      whose distribution is sharply peaked at 4.9 A followed by an exponential decay
      with increasing distance. Our main aims of this study are to understand the
      formation of helical kinks and to predict their structural features. Therefore we
      further performed molecular dynamics (MD) simulations under four simulation
      scenarios to investigate kink formation in 37 kinked TM helices and 5 unkinked TM
      helices. The representative models of these kinked helices are predicted by a
      clustering algorithm, SPICKER, from numerous decoy structures possessing the
      above generic features of kinked helices. Our results show an accuracy of 95 % in
      predicting the kink position of kinked TM helices and an error less than 10
      degrees  in the angle prediction of 71.4 % kinked helices. For unkinked helices,
      based on various structure similarity tests, our predicted models are highly
      consistent with their crystal structure. These results provide strong supports
      for the validity of our method in predicting the structure of TM helices.

PMID- 22996199
TI  - Adverse outcomes associated with nerve stimulator-guided and ultrasound-guided
      peripheral nerve blocks by supervised trainees: update of a single-site database.
AB  - BACKGROUND: We previously published a retrospective review of complications
      related to peripheral nerve blocks performed by supervised trainees, from our
      quality assurance and billing data, guided by either ultrasound, with nerve
      stimulator confirmation, or landmark-based nerve stimulator techniques. This
      report updates our results, for the period from May 2008 through December 2011,
      representing ongoing transition to near-complete combined ultrasound/nerve
      stimulator guidance in a block-oriented, outpatient orthopedic anesthesia
      practice. METHODS: We queried our deidentified departmental quality improvement
      electronic database for adverse outcomes associated with peripheral nerve blocks.
      Billing records were also deidentified and used to provide the denominator of
      total number of blocks using each technique of neurolocation. The types of blocks
      considered in this analysis were interscalene, axillary, femoral, sciatic, and
      popliteal-sciatic blocks. Nerve block complications based on each type of
      guidance were then compared for the entire recent 30-month time period, as well
      as for the 6-year period of this report. RESULTS: There were 9062 blocks
      performed by ultrasound/nerve stimulator, and 5436 by nerve stimulator alone over
      the entire 72-month period. Nerve injuries lasting longer than 1 year were rare,
      but similar in frequency with both nerve guidance techniques. The incidence of
      local anesthetic systemic toxicity was found to be higher with landmark-nerve
      stimulator technique than with use of ultrasound-guided nerve blocks (6/5436 vs
      0/9069, P = 0.0061). CONCLUSIONS: We report a large series of combined
      ultrasound/nerve stimulator nerve blocks by supervised trainees without major
      local anesthetic systemic toxicity. While lacking the compelling evidence of
      randomized controlled trials, this observational database nonetheless allows
      increased confidence in the safety of using combined ultrasound/nerve stimulator
      in the setting of anesthesiologists-in-training.

PMID- 22996200
TI  - Effect of acute versus continuous glycemic control on duration of local
      anesthetic sciatic nerve block in diabetic rats.
AB  - BACKGROUND AND OBJECTIVES: The duration of nerve block is longer in
      streptozotocin (STZ)-induced diabetic rats for all local anesthetics (with and
      without adjuvants) compared with normal rats. Perioperative glycemic control is
      currently practiced to reduce adverse events in many at-risk patients, especially
      in diabetic patients, to prevent neuropathy, poor wound healing, and greater
      incidence of infection. The aim of this study was to investigate in diabetic rats
      the importance of glycemic control before peripheral nerve block. METHODS: To
      induce diabetes, rats were intravenously injected with a single dose of 50 mg/kg
      STZ to destroy pancreatic beta cells. Tactile allodynia in response to von Frey
      filament stimulation of the plantar hind paws was used as the criterion for
      diabetic neuropathy. Diabetic rats were randomly divided into experimental
      treatment groups. The continuous glycemic control experiment compared: 3 U/d
      insulin implant for 14 days, 1.5 U/d insulin implant for 14 days, and placebo
      treatment. The acute glycemic control experiment compared a single 6U Human
      Insulin Isophane Suspension (NPH) injection and placebo treatment. Nondiabetic
      rats received placebo implants or injections. Following treatment, 0.1 mL of 1%
      lidocaine hydrochloride with 5 MUg/mL epinephrine hydrochloride was injected into
      the left sciatic notch. Animals were then reevaluated at 10-minute intervals for
      the absence or presence of sensory and motor response. RESULTS: All STZ-injected
      rats had blood glucose levels greater than 350 mg/dL and tactile allodynia. After
      insulin implants or injections, diabetic rats had much lower blood glucose levels
      than diabetic rats with placebo treatment. With both 3 and 1.5 U/d continuous
      glycemic control, the local anesthetic solution produced a shorter duration of
      sensory and motor nerve block in insulin-treated diabetic rats compared with
      placebo-treated diabetic rats, and shorter duration was similar to nondiabetic
      rats. With 6 U acute glycemic control in diabetic rats, there was no reduction in
      nerve block duration compared with placebo-treated diabetic rats. CONCLUSIONS:
      With continuous glycemic control in diabetic rats, the duration of sensory and
      motor nerve block was about 40 minutes shorter than that in the untreated
      diabetic rats and similar to that of normal rats. However, acute glycemic control
      did not affect nerve block duration, suggesting that this neuropathy cannot be
      rapidly reversed.

PMID- 22996201
TI  - Prolonged nerve block by microencapsulated bupivacaine prevents acute
      postoperative pain in rats.
AB  - BACKGROUND AND OBJECTIVES: To minimize acute postoperative pain, a new
      formulation of slowly released bupivacaine was developed. METHODS: Bupivacaine
      was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and
      characterized for physicochemical properties and bupivacaine release kinetics.
      This formulation was injected around the rat sciatic nerve to produce an
      antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral
      plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine
      slow-release formulation was placed at the ipsilateral sciatic nerve and compared
      with the hyperalgesia that developed with various controls. RESULTS: Bupivacaine
      was released in vitro at a relatively constant rate over a period of ~ 72 to 96
      hours. Complete antinociception, shown as no response to toe pinch, lasted for 23
      +/- 7 hours, with a half-recovery time of 42 +/- 8 hours after sciatic nerve
      injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine.
      Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete
      antinociception for less than 2 hours and recovery half-times of 2 hours.
      Postincisional mechanical hyperalgesia, shown by increased withdrawal responses
      to von Frey filaments, was absent for 24 hours and was lower than control for 96
      hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas
      the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours.
      CONCLUSIONS: Corresponding to its far greater functional blocking time, the
      microsphere-bupivacaine formulation was able to significantly reduce
      postoperative pain below control levels for up to 4 days. These findings of
      several days of postoperative pain relief, for an injectable formulation
      containing a single active agent, present an improved and potentially promising
      therapy to prevent acute pain after surgery.

PMID- 22996202
TI  - Three-times-daily subcutaneous unfractionated heparin and neuraxial anesthesia: a
      retrospective review of 928 cases.
AB  - BACKGROUND AND OBJECTIVES: Subcutaneous (SC) unfractionated heparin (UFH)
      administered 3 times daily (TID) is widely used for venous thromboembolism
      prophylaxis in the perioperative period. There are no data in the literature
      regarding the incidence of adverse outcomes with neuraxial analgesia in the
      setting of this regimen. In this retrospective review, we report the incidence of
      untoward events related to anticoagulation with SC UFH TID in patients with
      indwelling epidural catheters. METHODS: We queried the electronic hospital
      databases to identify patients receiving thoracic epidural analgesia in
      conjunction with 5000 U UFH SC TID from July 2008 to October 2010. In this group,
      we identified the diagnoses of neuraxial hematoma, deep vein thrombosis, or
      pulmonary embolism and examined measured blood coagulation parameters. In
      addition, we determined the percentage of patients receiving concomitant therapy
      with ketorolac. RESULTS: We identified 928 patients who received thoracic
      epidural analgesia in conjunction with 5000 U UFH SC TID during this period.
      There were no cases of neuraxial bleeding. Seven patients had a diagnosed deep
      vein thrombosis or pulmonary embolism. Thirty-four percent (315/928) of patients
      received ketorolac. The measured activated thromboplastin time was more than 40
      seconds (35 seconds being the upper limit of normal) in 115 patients (12%).
      CONCLUSIONS: Given the rare incidence of neuraxial hematoma, statements regarding
      the appropriateness of epidural analgesia in the setting of TID SC UFH cannot be
      made from this limited sample size. At present, information regarding epidural
      hematoma in the setting of a TID SC UFH dosing regimen does not exist in the
      literature. Our study represents an initial step in the accumulation of data
      needed to prove or disprove the safety of this practice.

PMID- 22996203
TI  - Access to enantiomerically pure cis- and trans-beta-phenylproline by high
      performance liquid chromatography resolution.
AB  - The preparation of all four stereoisomers of the proline analog that bears a
      phenyl group attached to the beta carbon either cis or trans to the carboxylic
      acid (cis- and trans-beta-phenylproline, respectively) has been addressed. The
      methodology developed allows access to multigram quantities of the target amino
      acids in enantiomerically pure form and suitably protected for use in peptide
      synthesis. Racemic precursors of cis-beta-phenylproline and trans-beta
      phenylproline were prepared from easily available starting materials and
      subjected to high-performance liquid chromatography enantioseparation.
      Semipreparative columns (250 * 20 mm) containing chiral stationary phases based
      on amylose (Chiralpak IA) (Daicel-Chiral Technologies Europe, Illkirch, France)
      or cellulose (Chiralpak IC) were used respectively for the resolution of the cis-
      and trans-beta-phenylproline precursors.

PMID- 22996204
TI  - Simultaneous confidence intervals on multivariate non-inferiority.
AB  - We discuss the analysis of non-inferiority trials based on a multi-armed design
      with multiple correlated endpoints. We consider five different scenarios: (1)
      global non-inferiority; (2) non-inferiority for subsets of comparisons; (3)
      global non-inferiority for a treatment group; (4) global non-inferiority for an
      endpoint; and (5) local non-inferiority. We describe and compare related
      approaches, which are based on the union-intersection and intersection-union test
      principles - alone and in combination. Because non-inferiority thresholds for
      many differently scaled endpoints are rarely available in practice, the
      approaches described focus on the estimation of simultaneous confidence limits
      and their post hoc interpretation on non-inferiority. We discuss and demonstrate
      pros and cons by means of a real data example.

PMID- 22996207
TI  - Illuminating the mechanism of the borane-catalyzed hydrosilylation of imines with
      both an axially chiral borane and silane.
AB  - The reduction of C=O groups with silanes catalyzed by electron-deficient boranes
      follows a counterintuitive mechanism in which the Si-H bond is activated by the
      boron Lewis acid prior to nucleophilic attack of the carbonyl oxygen atom at the
      silicon atom. The borohydride thus formed is the actual reductant. These steps
      were elucidated by using a silicon-stereogenic silane, but applying the same
      technique to the related reduction of C=N groups was inconclusive due to
      racemization of the silicon atom. The present investigation now proves by the
      deliberate combination of our axially chiral borane catalyst and axially chiral
      silane reagents (in both enantiomeric forms) that the mechanisms of these
      hydrosilylations are essentially identical. Unmistakable stereochemical outcomes
      for the borane/silane pairs show that both participate in the enantioselectivity
      determining hydride-transfer step. These experiments became possible after the
      discovery that our axially chiral C(6)F(5)-substituted borane induces appreciable
      levels of enantioinduction in the imine hydrosilylation.

PMID- 22996206
TI  - Are self-report measures of adaptive functioning appropriate for those high in
      psychopathic traits?
AB  - There is ongoing debate about the methods that evaluators should use to assess
      the adaptive functioning of an individual in an Atkins claim, including the
      appropriateness of using self-report measures and extent to which adaptive
      functioning measures are valid for persons with a history of violent offending.
      This study examined whether offenders' self-report adaptive functioning scores
      tended to decrease as their level of psychopathic traits increased. Eighty-five
      male felony probationers completed the self-report version of the Adaptive
      Behavior Assessment System - II (ABAS-II: Harrison & Oakland, 2003), the
      Psychopathic Personality Inventory - Revised (PPI-R: Lilienfeld & Widows, 2005),
      and a brief intelligence screening measure. ABAS-II composite scores were
      negatively correlated with PPI-R Self-Centered Impulsivity and Coldheartedness
      scores, but positively correlated with Fearless Dominance scores. These
      relationships appeared to be due, in part, to over-reporting symptoms of
      impairment across measures, suggesting that scores on self-report adaptive
      functioning measures may be especially susceptible to feigning.

PMID- 22996205
TI  - Circulating miRNAs: reflecting or affecting cardiovascular disease?
AB  - MicroRNAs are a class of small, noncoding RNAs encoded by the metazoan genome
      that regulate protein expression. A collection of studies point to vital roles
      for microRNAs in the onset and development of cardiovascular diseases. So far,
      microRNAs have been considered as important intracellular mediators in
      maintaining proper cardiac function and hemostasis, and have been proposed as
      potential therapeutic targets in cardiovascular disease. The recent discovery
      that microRNAs circulate in a stable form in many body fluids, including blood,
      suggests that circulating microRNAs can serve as a new generation of biomarkers
      for cardiovascular diseases. In this review, we summarize the findings of studies
      focusing on circulating microRNAs present in human blood cells or plasma/serum,
      where they potentially could serve as diagnostic or prognostic markers for a
      variety of cardiovascular pathologies, including acute myocardial infarction,
      heart failure, coronary artery disease, stroke, diabetes and hypertension. The
      significance and limitations of microRNAs as the new biomarker generation for
      cardiovascular disease are also discussed.

PMID- 22996208
TI  - Evaluation of an expanded case definition for vaccine-modified measles in a
      school outbreak in South Korea in 2010.
AB  - In this study, we have described the clinical characteristics of vaccine-modified
      measles  to assess the performance of an expanded case definition in a school
      outbreak that occurred in 2010. The  sensitivity, specificity, and the positive
      and negative predictive values were evaluated. Among 74 cases of  vaccine
      modified measles, 47 (64%) met the original case definition. Fever and rash were
      observed in 73%  (54/74); fever was the most common (96%, 71/74) presenting
      symptom, and rash was noted in 77% (57/74) of  the cases. The original case
      definition showed an overall sensitivity of 63.5% and a specificity of 100.0%. 
      The expanded case definition combining fever and rash showed a higher sensitivity
      (72.9%) but a lower  specificity (88.2%) than the original. The presence of fever
      and one or more of cough, coryza, or  conjunctivitis scored the highest
      sensitivity among the combinations of signs and symptoms (77.0%), but  scored the
      lowest specificity (52.9%). The expanded case definition was sensitive in
      identifying suspected  cases of vaccine-modified measles. We suggest using this
      expanded definition for outbreak investigation in  a closed community, and
      consider further discussions on expanding the case definition of measles for 
      routine surveillance in South Korea.

PMID- 22996209
TI  - Evaluation of TREM1 gene expression in circulating polymorphonuclear leukocytes
      and its inverse correlation with the severity of pathophysiological conditions in
      patients with acute bacterial infections.
AB  - During bacterial infection, activated polymorphonuclear leukocytes (PMNs) often
      cause  inflammation and organ dysfunction in severely ill patients. Gene
      expression was analyzed in circulating PMNs  isolated from these patients to
      determine the distinct expression profile. We focused on immunomodulatory genes, 
      such as those for pattern recognition receptors, inflammatory cytokines, PMN
      surface antigens, and myeloid cell  receptors in PMNs. Gene expression in 23
      patients (12 with pneumonia and 11 with sepsis) were analyzed using  quantitative
      real-time polymerase chain reaction. The mRNA levels of TLR2 (20/23 cases) and
      CD14 (18/23 cases)  were upregulated in the PMNs of patients when compared with
      healthy subjects. The mRNA expression levels of TLR4  (16/23 cases) and IL6
      (16/23 cases) were downregulated in patients' PMNs, and of TNFA (16/23 cases)
      were  upregulated in these cells. Although mRNA levels of IL8RA (15/23 cases)
      were downregulated in PMNs, MAC-1 mRNA  levels (14/23 cases) were upregulated in
      the same cells. Copies of the TREM1 transcript were 0.7- to 2.1-fold  higher in
      patients with moderate pneumonia than in the healthy subjects; the average fold
      change was 1.1. The  mRNA levels were 0.3-fold lower in the patients with severe
      pneumonia and sepsis than in the healthy subjects.  In conclusion, the
      downregulation of TREM1 expression in PMNs is associated with the severity of the
      pathophysiological conditions and may be used as a surrogate marker of acute
      bacterial infections.

PMID- 22996210
TI  - Pathological examination of lung tissues in influenza a virus-infected mice.
AB  - This study examined pathological changes in the lung tissues of young and aged
      mice infected  with influenza virus. Young mice inoculated with influenza virus
      showed body weight loss at 4 days  post-infection (dpi), meanwhile body weight
      decrease started from 9 dpi in the aged mice. We  histopathologically examined
      the lungs of these mice. Immunohistochemical examination revealed that viral 
      antigen-positive bronchiolar and alveolar epithelial cell numbers at 3 dpi were
      significantly higher in  young mice than in the aged ones. Further, viral antigen
      positive cells were observed at 9 dpi in the aged  mice, but not in the young
      ones. Diffuse and severe bronchointerstitial pneumonia characterized by the 
      accumulation of polymorphonuclear leukocytes (PMNs) was observed in young mice at
      6 dpi. Histopathological  changes in the aged mice were milder than those in the
      young mice. Moreover, T cell and macrophage  accumulation in the lungs was
      significantly higher in the young mice than in the aged mice at 9 dpi. These 
      results suggest that there may be a correlation between the relatively low level
      of infiltration of PMNs,  macrophages, and T lymphocytes and the delayed body
      weight loss and longer lasting infections observed in  the lungs of the aged
      mice. These findings provide detailed insights into the age-specific course of 
      infection in young and aged populations with associated differences in lung
      pathology.

PMID- 22996211
TI  - Health-related quality of life and the prevalence of post-traumatic stress
      disorder among Crimean-Congo hemorrhagic fever survivors.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal infectious disease,
      and it is  endemic in Turkey. Patients are placed in isolation when hospitalized,
      and some may require blood transfusions.  Moreover, some patients may require
      admission to intensive care units (ICU). CCHF is not a recurrent disease, and 
      relapses are not expected. Therefore, no medical follow-up is conducted on
      recovery from CCHF. In this study,  health-related quality of life (HRQL) and the
      presence of post-traumatic stress disorder (PTSD) among CCHF  survivors were
      evaluated 12 months after recovery from the disease. PTSD diagnosis was
      established by DSM-IV-TR  criteria and HRQL was investigated by using the Medical
      Outcomes Study Short Form 36. This study included 54  patients. Our results
      showed that 48.1% of the patients had PTSD symptoms and 18.5% had PTSD. PTSD
      incidence was  higher among patients who required an ICU stay, who had bleeding,
      and who required blood transfusion. In  addition, 4 out of 8 dimensions of HRQL
      were impaired. However, none of these patients admitted psychiatric  problems to
      health care professionals. Our findings revealed that periodic psychiatric
      evaluation should be  performed on CCHF patients, and they should be provided
      medical support, if required.

PMID- 22996212
TI  - Prevalence of immunity presumed using rabies vaccination history and household
      factors associated with vaccination status among domestic dogs in Japan.
AB  - Rabies was eliminated in Japan over 50 years ago; however, the recent increase in
      the movement of humans and animals across the world highlights the potential
      threat of disease  reentry into the country. The immune status against rabies
      among the dog population in Japan is  not well known; thus, the purpose of this
      study was to estimate the prevalence of dogs with  effective immunity from the
      vaccination history using a web-based survey. We found that 76.9%  (95%
      confidence interval, 75.8-78.1) of dogs in this study population belonged to the
      population  in which 90% were assumed to have the internationally accepted
      antibody titer. We showed that  dogs taken less frequently for walks were less
      likely to be vaccinated. Additionally, the  frequency of encounters with other
      dogs during walks and the number of individuals in households  were associated
      with vaccination history. To our knowledge, this study is the first report 
      estimating the prevalence of dogs in Japan with effective immunity against
      rabies. Further, we  identified the population with low vaccination coverage as
      well as the heterogeneous  characteristics of vaccination history among the dog
      population. These findings contribute to  the implementation of an efficient
      strategy for improving the overall vaccination coverage in  Japan and the
      development of a quantitative risk assessment of rabies.

PMID- 22996213
TI  - Qualitative analysis of the perception and acceptability of pathogen transport
      among housewives using focus group interviews.
AB  - We conducted focus group interviews to understand how residents of Japan feel 
      about the transport of pathogens. Twelve randomly selected housewives, who had no
      special  knowledge regarding the topic before the interview, expressed their
      opinions in 2 separate  meetings regarding pathogen transport. The results of the
      interviews were analyzed by the KJ  method. The analysis found that although the
      transport of pathogens is universally  recognized to be necessary, there is not
      clear consensus on the exact methods of transport,  the positive and/or negative
      value of such information, and how clearly and/or uniquely to  label containers,
      packages, compartments, vehicles, and conditions used for such  transportation.
      Further studies to improve the skills of both the providers and receivers of 
      such information (a technique of risk communication) are necessary.

PMID- 22996214
TI  - Post-pandemic seroprevalence of 2009 pandemic influenza A (H1N1) virus in
      Shandong Province, China.
AB  - The purpose of this study was to understand the geographic extent, risk factors,
      and attack rate of  the 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09]
      infection in Shandong Province, China and to  identify the influencing factors. A
      randomized serological survey of A(H1N1)pdm09 infection was carried out in 
      August and September 2010. A total of 4,549 participants involved in the survey
      had their antibody levels  tested by hemagglutination-inhibition assay. The
      overall seropositive rate for A(H1N1)pdm09 antibodies was  25.85%. The
      seropositive rate was 25.89% for the unvaccinated group, with statistically
      significant  differences among individuals of different age groups, occupations,
      and cities. The highest seropositive rate  was observed in young children aged 0
      5 years and elderly people aged >=60 years. Multivariate logistic  regression
      revealed that subjects in rural areas had significantly higher odds ratio of
      A(H1N1)pdm09 seropositivity  than those in the capital city. Individuals
      belonging to all professions, except for teachers, had  significantly lower odds
      ratio of A(H1N1)pdm09 seropositivity compared with children in family care. Our
      data  indicated that almost 26% of the residents in Shandong Province had
      appropriate antibody titers against  A(H1N1)pdm09. This seroepidemiology study
      provides valuable data for understanding the epidemiology of the  2009 pandemic
      influenza and for planning future intervention strategies; moreover, it
      highlights the  significance of seroprevelance studies.

PMID- 22996215
TI  - Quantification of periodontopathic bacteria in saliva using the invader assay.
AB  - When quantifying periodontopathic bacteria, it is important to use a convenient
      method that  does not produce false negative results. The Invader assay is a
      convenient method because it does not involve  gene amplification. The purpose of
      this study was to evaluate the validity of the Invader assay to quantify 
      periodontopathic bacteria. The Invader technology was applied in quantifying five
      periodontopathic bacteria  (Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis, Tannerella forsythia, Prevotella intermedia,  and Treponema
      denticola). The Invader assay produced a linear quantitative detection range over
      concentrations  spanning seven exponential values, with a detection limit of
      10(3.7) copies/tube and intra-day and inter-day  variance of 0.1% to 4.7% and
      0.1% to 3.4%, respectively, in quantifying five periodontopathic bacteria. We 
      compared the results of the Invader assay with those of real-time polymerase
      chain reaction (PCR) performed for  quantifying five periodontopathic bacteria in
      22 patients with periodontitis. Among the Invader-detectable  bacterial strains
      of each species, significant correlations were observed in the counts of
      concerned bacterial  species between these two methods, with correlation
      coefficients ranging from 0.757 to 0.996. This study  validated repeatability and
      reproducibility of the Invader assay in quantifying periodontopathic bacteria and
      demonstrated consistent agreement between the Invader assay and real-time PCR in
      quantifying periodontopathic  bacteria.

PMID- 22996216
TI  - Human immunodeficiency virus seroprevalence among patients attending a sexually
      transmitted disease clinic in West Bengal, India.
AB  - Sexually transmitted infections (STIs) such as human immunodeficiency virus (HIV)
      infection have become  a major public health problem globally as well as in
      India. Prevalence of STIs varies across different high  risk groups including the
      population with sexually transmitted diseases (STDs). Individuals with STDs are
      at a  higher risk of acquisition of HIV through the sexual route than the other
      routes. The tendency of HIV infection  was studied in attendees aged 15-49 years
      in an STD clinic in West Bengal from 2004 to 2008. Blood samples were  collected
      consecutively from 250 attendees per year (a total of 1,250 samples over 5 years)
      from an STD clinic  during 12 weeks (October-December) every year. HIV sero
      status was screened using ELISA, and positive samples  were subjected to rapid
      assay and confirmed by Western blot. Overall HIV seropositivity in STD patients
      was  1.28% (women, 1.04%; men, 1.48%). Data from 5 consecutive years showed a
      prominent decline from 2.40% (2004) to  0.0% (2007) and a minor increase (1.6%)
      in 2008, which was not statistically significant (chi(2) = 4.6, df = 4,  P >
      0.05). The highest seroprevalence (1.66%) was observed in the 25-29 age group,
      and the lowest (0.87%) was  observed in the 40-44 age group. The overall
      decreasing tendency of HIV infections signifies the efficiency of  current
      interventions. Focused intervention for the 25-29 age group may help in
      decreasing HIV infections  further.

PMID- 22996217
TI  - A retrospective study of the extensive eradication program for brucellosis
      outbreaks and control in Korea, 2002-2009.
AB  - This study concerns the quantitative analysis of brucellosis outbreaks and the
      related risk  factors and control programs for both domestic cattle and human
      brucellosis infections in Korea between  2002 and 2009. There were a total of
      77,082 infections of bovine brucellosis (BB) in domestic cattle with a 
      prevalence rate (PR) of 13.3 per 1,000 cattle; during the same period there were
      620 cases of human  brucellosis (HB) with a PR of 0.16 per 100,000 persons.
      Moreover, the correlation coefficient of  brucellosis outbreaks between cattle
      and humans was highly significant (r = +0.985). The attack ratio of HB  cases was
      8.04 per 1,000 BB cases. The distribution of brucellosis outbreaks was
      concentrated in the  southeast region of Korea (P < 0.01). Significantly more
      males were infected than females (86.9% versus  13.1%), and a high incidence of
      HB was observed in those aged more than 40 years (86.1%). The majority of  HB
      cases occurred primarily among rural inhabitants (92.3%) and among famers and
      related workers (47.9%).  Finally, all of the measures that were applied in the
      extensive eradication program for brucellosis  outbreaks and control were based
      principally on an intensive test-and-slaughter policy and contributed 
      significantly to the reduction in the outbreaks of brucellosis in Korea.

PMID- 22996218
TI  - Detection of five rash-associated viruses using multiplex real-time PCR during
      2006-2011.
AB  - Many viruses have been reported to be associated with rash development. Multiplex
      real-time  PCR was used to investigate the presence of 5 viruses associated with
      rashes: measles virus (MV), rubella  virus (RV), human parvovirus B19 (PVB19),
      human herpes virus 6 (HHV-6), and HHV-7. A total of 187 clinical  specimens from
      169 patients with erythema were collected between January 2006 and December 2011.
      Virus-positive specimens were as follows: MV (n = 23), PVB19 (n = 8), RV (n =
      2), HHV-6 (n = 5), HHV-7  (n = 1), MV and PVB19 (n = 1), and HHV-6 and HHV-7 (n =
      1). All of the MV-positive specimens were collected  in 2007 and the strains
      whose sequence were available (21/24, 87.5%) were of genotype D5. The results 
      indicate that multiplex real-time PCR might be a useful screening method for
      detecting and differentiating  rash-associated viruses in clinical specimens.

PMID- 22996219
TI  - Ceftriaxone resistance and genes encoding extended-spectrum beta-lactamase among
      non-typhoidal Salmonella species from a tertiary care hospital in Kuala Lumpur,
      Malaysia.
AB  - The prevalence of ceftriaxone resistance and the associated genes encoding
      extended-spectrum beta-lactamase  (ESBL) was determined in 149 non-duplicate non
      typhoidal Salmonella isolated in 2008-2009 from  patients in a tertiary care
      hospital in Kuala Lumpur, Malaysia. The resistance rate to ceftriaxone was  2.7%
      (2/74) in 2008, 4.0% (3/75) in 2009, and 3.4% (5/149) overall. CTX-M ESBL genes
      were detected in 2 of  the 5 ceftriaxone-resistant isolates. The prevalence of
      ceftriaxone resistance, although low, is a concern  because it limits therapeutic
      options. Continued surveillance of ceftriaxone resistance is important to 
      monitor its trends.

PMID- 22996220
TI  - Inter-laboratory validation and applications of quantitative real-time PCR for
      the detection of Kudoa septempunctata in olive flounder (Paralichthys olivaceus).
AB  - Kudoa septempunctata, a myxosporean parasite, was recently identified as the
      causative agent of food poisoning resulting from the consumption of raw olive
      flounder (Paralichthys olivaceus). A single blind inter-laboratory study,
      involving 5 laboratories, was conducted to validate a quantitative real-time PCR
      assay for the detection of the parasite. We obtained relatively constant values
      for log rDNA copies/g from these laboratory analyses (SD = 0.35-0.86), suggesting
      the validity of the real-time PCR method for the detection of K. septempunctata
      in P. olivaceus. Detection of K. septempunctata in muscle tissue samples
      collected from both sides of the fish indicated that K. septempunctata infection
      spreads throughout the body of P. olivaceus. K. septempunctata infection in P.
      olivaceus is thought to occur during the early stage of fish growth because a K.
      septempunctata gene was detected in 1 of 300 P. olivaceus fry tested. Feeds seem
      not to be sources of infection. To prevent food poisoning due to K.
      septempunctata, the mechanism of infection and proliferation of K. septempunctata
      in P. olivaceus should be elucidated, and other hosts of the parasite should be
      identified. The sensitive real-time PCR method described here will be a useful
      tool for resolving these issues.

PMID- 22996221
TI  - Isolation and molecular characterization of catalase-negative Staphylococcus
      aureus from sputum of a patient with aspiration pneumonia.
AB  - Staphylococcus aureus produces various virulence factors. The catalase enzyme, in
      particular,  is considered to be involved in oxidative stress resistance, and
      catalase activity is an important criterion  for differentiating staphylococci
      from streptococci. In this report, we describe the catalase-negative S.  aureus
      strain SH3064, which was isolated from the sputum of a patient with aspiration
      pneumonia. To evaluate  the causes of the lack of catalase activity in S. aureus
      SH3064, we analyzed the sequence of katA gene  encoding the catalase enzyme in
      this strain. We amplified the complete sequence of katA gene of S. aureus  SH3064
      by polymerase chain reaction using 2 sets of primers. The katA sequence showed
      99.6% sequence  identity (1512/1518 bp) with that of S. aureus ATCC 12600. We
      detected 2 mutations in the katA gene from S.  aureus SH3064, an A217T
      substitution leading to a threonine 73-to-serine substitution and a single-base 
      pair deletion (c.637delG) resulting in a frameshift mutation. The lack of
      catalase activity in this strain  was attributed to the shift of the nucleotide
      reading frame.

PMID- 22996222
TI  - Does levofloxacin induce hemolytic uremic syndrome in patients infected with
      verotoxin-producing Escherichia coli O157 infections?
AB  - Fifteen Japanese colitis patients, aged above 16 years old, infected with
      verotoxin-producing  Escherichia coli O157 (VTEC O157) were divided into 2
      treatment groups. Of the 15 patients, 6 (mean +/- SD,  41.3 +/- 19.0 years old)
      were treated with levofloxacin (LVFX), while the remaining 9 patients (32.0 +/-
      10.0  years old) were not treated with any antimicrobial agents. All patients
      complained of abdominal pain and  bloody stool and were not administered
      antidiarrheals. Hemolytic uremic syndrome (HUS) did not develop in  any of the 6
      patients treated with LVFX, but developed in 1 of the 9 patients not treated with
      antimicrobial agents. No statistical difference was found in the occurrence rate
      of HUS between  LVFX-treated patients and patients not treated with antimicrobial
      agents. Our results suggest that oral  administration of LVFX is not associated
      with risk of HUS in hemorrhagic colitis patients aged above 16  years infected
      with VTEC O157.

PMID- 22996223
TI  - Detection of exanthematic viruses using a TaqMan real-time PCR assay panel in
      patients with clinically diagnosed or suspected measles.

PMID- 22996224
TI  - Follow-up survey of Japanese encephalitis virus infection in Kumamoto Prefecture,
      South-West Japan: status during 2009-2011.

PMID- 22996225
TI  - Negative impacts of large population size and high population density on the
      progress of measles elimination.

PMID- 22996226
TI  - Identification of a G8P[14] rotavirus isolate obtained from a Taiwanese child:
      evidence for a relationship with bovine rotaviruses.

PMID- 22996227
TI  - Isolation of an intertypic recombinant human adenovirus (candidate type 56) from
      the pharyngeal swab of a patient with pharyngoconjunctival fever.

PMID- 22996228
TI  - Enteroviruses in patients experiencing multiple episodes of hand, foot, and mouth
      disease in the same season in Kobe, Japan, 2011.

PMID- 22996229
TI  - Possible pulmonary cryptococcosis in a patient with Crohn's disease during anti
      tumor necrosis factor-alpha treatment: a case report and literature review.

PMID- 22996230
TI  - Integration of synchronous synaptic input in CA1 pyramidal neuron depends on
      spatial and temporal distributions of the input.
AB  - Highly synchronized neural firing has been discussed in relation to learning and
      memory, for instance sharp-wave activity in hippocampus. We were interested to
      study how a postsynaptic CA1 pyramidal neuron would integrate input of different
      levels of synchronicity. In previous work using computational modeling we studied
      how the integration depends on dendritic conductances. We found that the
      transient A-type potassium channel K(A) was able to selectively suppress input of
      high synchronicity. In recent years, compartmentalization of dendritic
      integration has been shown. We were therefore interested to study the influence
      of localization and pattern of synaptic input over the dendritic tree of the CA1
      pyramidal neuron. We find that the selective suppression increases when synaptic
      inputs are placed on oblique dendrites further out from the soma. The suppression
      also increases along the radial axis from the apical trunk out to the end of
      oblique dendrites. We also find that the K(A) channel suppresses the occurrence
      of dendritic spikes. Moreover, recent studies have shown interaction between
      synaptic inputs. We therefore studied the influence of apical tuft input on the
      integration studied above. We find that excitatory input provides a modulatory
      influence reducing the capacity of K(A) to suppress synchronized activity, thus
      facilitating the excitatory drive of oblique dendritic input. Conversely,
      inhibitory tuft input increases the suppression by K(A) providing a larger
      control of oblique depolarizing factors on the CA1 pyramidal neuron in terms of
      what constitutes the most effective level of synchronicity. Furthermore, we show
      that the selective suppression studied above depends on the conductance of the
      K(A) channel. K(A) , as several other potassium channels, is modulated by several
      neuromodulators, for instance acetylcholine and dopamine, both of which have been
      discussed in relation to learning and memory. We suggest that dendritic
      conductances and their modulatory systems may be part of the regulation of
      processing of information, in particular for how network synchronicity affects
      learning and memory.

PMID- 22996232
TI  - The influence of locomotive syndrome on health-related quality of life in a
      community-living population.
AB  - OBJECTIVES: The Japanese Orthopaedic Association (JOA) has proposed the term
      "locomotive syndrome" (LS) to designate a condition in individuals with
      musculoskeletal disease in high-risk groups who are highly likely to require
      nursing care. The present study investigated the influence of LS on the quality
      of life (QOL) of a community-living population. METHODS: A total of 386 subjects
      >= 50 years of age were enrolled in the study. Those whose scores on the 25
      question Geriatric Locomotive Function Scale were >=16 were defined as having LS.
      Participants answered the JOA Back Pain Evaluation Questionnaire (JOABPEQ) and
      visual analogue scales (VAS) for low back pain, leg pain, leg numbness, and left
      and right knee pain; the Roland Morris Disability Questionnaire (RDQ); and the
      Short Form 36 (SF-36). We compared the scores on the three QOL measures between
      subjects diagnosed with and without LS. RESULTS: There were 62 people defined as
      having LS. Subjects with LS scored significantly lower on the JOABPEQ and SF-36
      than those without LS. They also had significantly higher scores on the five VASs
      and the RDQ compared with those without LS. CONCLUSIONS: We found that LS
      strongly impacted QOL and the scores from the VASs. LS appears to be a useful
      concept for screening subjects who are experiencing a lowered QOL due to
      musculoskeletal diseases, especially degenerative lumbar diseases and knee
      osteoarthritis.

PMID- 22996233
TI  - Altered autophagy gene expression and persistent atrophy suggest impaired
      remodeling in chronic hemiplegic human skeletal muscle.
AB  - INTRODUCTION: Upper motor neuron lesions after stroke are a major cause of
      disability. We aimed to determine whether skeletal muscles from these patients
      display typical molecular signatures of inflammation, growth arrest, and atrophy.
      METHODS: Muscle biopsies were analyzed for morphological, histochemical,
      ultrastructural, and molecular features indicative of changes in gene expression
      involved in muscle atrophy. RESULTS: Chronic hemiplegia resulted in ~9.5%
      atrophy, fiber type shifts, and histochemical and ultrastructural signs of
      impaired remodeling. TNF and TWEAK expressions were unaltered, but MSTN mRNA was
      lower (-73%, P < 0.05) in paretic tibialis anterior vs. age-matched controls. The
      expression of autophagy-related genes (BCN-1, LC3, and GABARAPL1) was lower in
      paretic tibialis anterior (-81%, -48%, and -60%, respectively, P < 0.01) and
      soleus (-85%, -54%, and -60% respectively, P < 0.01) compared with old controls.
      CONCLUSIONS: Persistent atrophy in chronic spastic hemiplegia may be associated
      with impaired remodeling partly due to altered autophagy gene expression.

PMID- 22996231
TI  - Gene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and
      inhibiting NF-kappaB signaling improves the efficacy of immunotherapy in a brain
      cancer model.
AB  - Immune-mediated gene therapy using adenovirus expressing Flt3 ligand and
      thymidine kinase followed by ganciclovir administration (Flt3/TK) effectively
      elicits tumor regression in preclinical glioma models. Herein, we assessed new
      strategies to optimize Flt3L/TK therapeutic efficacy in a refractory RG2
      orthotopic glioblastoma model. Specifically, we aimed to optimize the therapeutic
      efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following
      genes within the brain tumor microenvironment: 1) a TK mutant with enhanced
      cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half
      life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing
      dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)
      10, 5) C-C motif ligand 2 chemokine (CCL2) or C-C motif ligand 3 chemokine (CCL3)
      to enhance dendritic cell recruitment into the tumor microenvironment, 6) T
      helper cell type 1 cytokines interferon-gamma or interleukin-2 to enhance
      effector T-cell functions, and 7) IkappaBalpha or p65RHD (nuclear factor kappa-B
      [NF-kappaB] inhibitors) to suppress the function of Foxp3+ Tregs and enhanced
      effector T-cell functions. Anti-tumor immunity and tumor specific effector T-cell
      functions were assessed by cytotoxic T lymphocyte assay and intracellular IFN
      gamma staining. Our data showed that overexpression of interferon-gamma or
      interleukin-2, or inhibition of the nuclear factor kappa-B within the tumor
      microenvironment, enhanced cytotoxic T lymphocyte-mediated immune responses and
      successfully extended the median survival of rats bearing intracranial RG2 when
      combined with Flt3L/TK. These findings indicate that enhancement of T-cell
      functions constitutes a critical therapeutic target to overcome immune evasion
      and enhance therapeutic efficacy for brain cancer. In addition, our study
      provides novel targets to be used in combination with immune-therapeutic
      strategies for glioblastoma, which are currently being tested in the clinic.

PMID- 22996234
TI  - Semiquantitative analysis and characterization of physiological biodistribution
      of (68)Ga-DOTA-TATE PET/CT.
AB  - The aim of this study was to describe the normal physiological distribution of
      (68)Ga-DOTA-TATE using the SUV to reflect the density of somatostatin receptors
      in various organ systems. METHODS: A total of 250 patients (90 men and 160 women)
      were imaged on a Biograph 64 PET/CT TruePoint (Siemens Medical Solutions) 60 to
      80 minutes after injection of 120 to 200 MBq (3.2-5.4 mCi) of (68)Ga-DOTA-TATE.
      Visual assessment was performed on all studies on the multimodality workstation,
      and sites of increased uptake were recorded. The SUVmax was also calculated for
      each organ demonstrating increased (68)Ga-DOTA-TATE uptake. RESULTS: Visual
      assessment of the (68)Ga-DOTA-TATE PET/CT studies revealed increased uptake in
      the pituitary, salivary, thyroid glands, liver, spleen, adrenals, kidneys and
      bone reflecting normal increased somatostatin receptor expression. These sites
      were confirmed to be disease free on clinical follow-up and on correlation with
      other imaging (CT/MRI/ultrasound). Using semiquantitative analysis, SUVmax values
      were the highest in the pituitary gland [11 (4.5)], spleen [18.9 (6.6)], adrenal
      [14.0 (5.6)], and kidneys [14.2 (3.6)]. In addition, increasing uptake in the
      uncinate process of pancreas was noted in 12% of patients with SUVmax of 9.2
      (3.3). Moderate (68)Ga-DOTA-TATE uptake was also present in salivary gland [3.4
      (1.8)], thyroid [2.9 (1.2)], and normal liver [6.5 (2.2)]. The bones generally
      showed low (68)Ga-DOTA-TATE uptake with an SUVmax of 1.0 (0.3). CONCLUSIONS:
      Knowledge of the normal (68)Ga-DOTA-TATE distribution is highly important for
      accurate interpretation of this novel imaging modality, which is increasingly
      being used in the imaging of neuroendocrine tumor.

PMID- 22996235
TI  - Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.
AB  - PURPOSE: Our aims were to assess the feasibility of imaging hypoxia in cervical
      carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare
      (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. PATIENTS AND METHODS: We
      included 16 patients with cervical carcinoma. After imaging with FDG, (18)F
      FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed.
      (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker
      of hypoxia, and patients' outcomes. RESULTS: All tumors were detected by (18)F
      FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant
      correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake
      (T/M > 3.2) was associated with reduced progression-free survival (log-rank =
      0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662
      MUg/L (median, 102.5 MUg/L). Patients with OPN greater than 144 MUg/L had reduced
      progression-free survival compared with those with OPN less than 144 MUg/L (log
      rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and
      OPN blood levels. CONCLUSIONS: Our preliminary results showed that a high uptake
      of (18)F-FETNIM was associated with a worse progression-free and overall
      survival.

PMID- 22996236
TI  - Lean body mass is better than body surface area in correcting GFR.
AB  - PURPOSE: The Gates-based renography (gGFR) and plasma-based clearance rate (pGFR)
      are conventionally corrected with body surface area (BSA). Limited studies
      indicated that the lean body mass (LBM) might be better than BSA in correcting
      pGFR. Therefore, we suggest that LBM is also better in correcting gGFR and
      improve the correlation coefficient between gGFR and pGFR. METHOD: During June
      2009 and December 2010, the gGFR and pGFR of 63 patients with hydronephrosis were
      measured and corrected with BSA and LBM, respectively. The correlation and
      regression analyses were conducted to illustrate the power of BSA and LBM
      correction. RESULTS: In a paired t test, there was no significant difference
      between pGFR and gGFR in patients with stages 1 and 2, although this was
      significant in stages 3 and 4. However, neither LBM nor BSA correction could
      eliminate the difference. In all patients (N = 63), the correlation coefficient
      (r) between pGFR and gGFR was 0.794 (P <; 0.001). After the BSA and LBM
      correction, r was improved to 0.809 and 0.828, respectively. In all patients, the
      regression line of pGFR(LBM) - gGFR(LBM) was nearer to the original point and its
      slope closer to 1 than pGFR(BSA) - gGFR(BSA) and pGFR - gGFR. Similar results
      were found in the analysis of most stages and subgroups. CONCLUSIONS: The
      commonsense of BSA correction should be seriously reevaluated. Lean body mass can
      better improve the correlation coefficient between paired GFRs than BSA can and
      it can be suitable in the correction.

PMID- 22996237
TI  - Air leaks localized with lung ventilation SPECT.
AB  - A 61-year-old man with severe chronic obstructive pulmonary disease presented to
      our hospital with recurrence of a right-sided spontaneous secondary pneumothorax.
      Thoracoscopic abrasion of the parietal pleura was performed, but an important air
      leak persisted. Presumed to originate from a bulla in the right upper lobe,
      bullectomy and pleural decortication were performed, but leakage remained.
      Lobectomy was considered, and quantitative ventilation/perfusion SPECT was
      performed to predict the functional outcome.Fused high-resolution CT/Tc Technegas
      images localized leakage not only to a bleb in the right upper lobe but also to
      the subcutaneous emphysema in the thoracic wall. The air leak resolved after
      conservative treatment.

PMID- 22996238
TI  - Intraindividual comparison of 123I-mIBG SPECT/MRI, 123I-mIBG SPECT/CT, and MRI
      for the detection of adrenal pheochromocytoma in patients with elevated urine or
      plasma catecholamines.
AB  - PURPOSE: To determine the diagnostic performance of 123I-metaiodobenzylguanidine
      (mIBG) SPECT/MRI fusion, 123I-mIBG SPECT/CT and adrenal MRI for the detection of
      pheochromocytoma in patients with elevated urine or plasma catecholamines.
      PATIENTS AND METHODS: Twenty-two consecutive patients underwent both a whole-body
      123I-mIBG scan with SPECT/CT of the adrenal region and MRI of the adrenal glands.
      Fused SPECT/MRI, SPECT/CT, and MRI scans were evaluated. Imaging results were
      analyzed both on a per-patient and on a per-lesion basis. Histopathology and/or
      clinical and radiological follow-up served as the reference standard. RESULTS:
      Sixteen adrenal tumors were found in thirteen patients. On a per-lesion basis,
      SPECT/CT had a sensitivity of 87.5%, a specificity of 93.8%, and an overall
      accuracy of 92.5%. MRI had a sensitivity of 87.5%, a specificity of 96.9%, and an
      overall accuracy of 95.0%. On a per-patient basis, both SPECT/CT and MRI had a
      sensitivity of 85.7%, a specificity of 93.3%, and an overall accuracy of 90.9%.
      SPECT/CT was concordant with MRI in 81.8% of cases. SPECT/MRI fusion was superior
      to both SPECT/CT and MRI and had a sensitivity of 100% on both a per-lesion and a
      per-patient basis. CONCLUSIONS: 123I-mIBG SPECT/MRI has the highest sensitivity
      and accuracy for the detection and localization of pheochromocytomas. SPECT/CT
      and MRI of the adrenal glands are equivalent diagnostic procedures. However, MRI
      offers the advantage of fully diagnostic assessment of adrenal lesions other than
      pheochromocytoma undetectable by 123I-mIBG.

PMID- 22996239
TI  - FDG-PET/CT findings of peritoneal lymphomatosis.
AB  - Peritoneal lymphomatosis (PL) is an extensive lymphomatous infiltration of the
      intraperitoneal portion of the subperitoneal space, which is a rare presentation
      of lymphoma. Using CT or MRI findings alone, it is difficult to differentiate
      between lymphomatosis, carcinomatosis, and other pathological entities.We
      experienced two PL cases and herein report the FDG-PET/CT findings. High FDG
      uptakes were found in omental and peritoneal infiltration, gastric wall
      involvement, and lymph node involvement in the epiphrenic region, although
      retroperitoneal lymph node involvement was absent. Systemic abnormal FDG uptakes
      suggested PL rather than carcinomatosis, and FDG-PET/CT findings were useful for
      the diagnoses.

PMID- 22996240
TI  - Incidental detection of gastrointestinal bleeding from an aortoenteric fistula on
      99mTc leukocyte scintigraphy.
AB  - A 50-year-old-man with abdominal pain, who had undergone aortic aneurysm
      reconstructive surgery (aortic graft) 3 years before, was admitted to the
      hospital. A CT scan showed findings suggestive of perigraft infection.
      Scintigraphy with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labeled
      leukocytes confirmed the diagnosis of aortic graft infection and documented an
      active concurrent bleeding in the gastrointestinal tract from a secondary
      aortoenteric fistula. This case illustrates the diagnosis of the precise location
      of the source of bleeding from aortoenteric fistula by leukocyte scintigraphy.
      The images aided the surgical team by revealing the aortic site of bleeding and
      the severity of the problem.

PMID- 22996241
TI  - Intense FDG activity in a case of xanthogranulomatous cholecystitis without
      elevated fluorothymidine activity.
AB  - F-FDG PET/CT is a useful imaging modality to detect malignant gall bladder
      lesions. We present an image of a patient with a gall bladder mass that was found
      to be FDG avid but negative on F-fluorothymidine PET/CT imaging. This was later
      confirmed to be a case of xanthogranulomatous cholecystitis.

PMID- 22996242
TI  - Is there a role for radioguided surgery with iodine-labeled
      metaiodobenzylguanidine in resection of neuroendocrine tumors?
AB  - PURPOSE: The aim of this study was to systematically review literature, exploring
      the role of radioguided surgery with iodine-labeled metaiodobenzylguanidine
      (MIBG) in resection of neuroendocrine tumors. METHODS: PubMed, EMBASE, Web of
      Science, COCHRANE, CINAHL, Academic Search Premier, ScienceDirect, Wiley, and
      references of key articles were searched to identify potentially relevant
      studies. RESULTS: Twenty studies were included. A total of 130 procedures in 120
      patients were performed. Ninety percent of included studies concerned case
      reports or case series. It is described that radioguided surgery with iodine
      labeled MIBG can improve the quality of macroscopic resection of neuroendocrine
      tumors in selected cases, ie, in cases where the tumor is small, nonpalpable,
      difficult to visualize on conventional imaging studies, or located in an area
      with adhesional scar tissue from previous surgery. However, in a substantial
      number of cases the gamma probe failed due to technical problems. CONCLUSIONS:
      Since there is limited evidence that radioguided surgery contributes
      substantially in resection of neuroendocrine tumors, we cannot advocate its use
      in general. However, we can conclude that it can seemingly improve the quality of
      resection in selected cases. When radioguided surgery is performed in
      neuroendocrine tumors, we advocate the use of I to label MIBG.

PMID- 22996243
TI  - FDG injection site extravasation: potential pitfall of misinterpretation and
      missing metastases.
AB  - 18F-FDG PET/CT plays an important role in the management of non-small-cell lung
      cancers (NSCLC). The treatment options for NSCLC depend upon the initial staging
      of the disease. The authors report a case with a potential pitfall of overlooking
      a site of FDG uptake as radiopharmaceutical extravasation at an injection site.
      The PET/CT demonstrated a T2a N2 bronchial carcinoma, with a solitary focus of
      FDG uptake at the left antecubital fossa where FDG was administered. Careful
      interpretation of the images reveals a solitary skeletal metastasis in the left
      proximal ulna, which makes the disease stage IV rather than IIIA, leading to a
      significant difference in treatment.

PMID- 22996244
TI  - "Bulky mass":  metastasis of poorly differentiated follicular thyroid carcinoma:
      a case report.
AB  - Poorly differentiated follicular thyroid carcinoma (PDFC) is a tumor of
      follicular cell origin with intermediate attributes between well-differentiated
      carcinomas and anaplastic carcinomas. The majority of patients presenting with
      distant metastases have locally advanced tumors, being lungs and bones the most
      common sites affected. We present a case of a patient with a painful bulky mass
      at the left thorax-abdominal wall as an uncommon distant metastasis of a PDFC.
      After thyroidectomy, a pre-ablative 131I whole-body scan showed distant
      metastases on the neck, both lungs, and lateral chest-abdominal wall, so the
      administration of I for thyroid remnant ablation stimulated with RH-TSH was
      decided.

PMID- 22996245
TI  - Axillary lymph node metastasis of papillary thyroid carcinoma detected by FDG
      PET/CT in a thyroglobulin-positive patient with negative whole-body 131I scan.
AB  - Axillary metastasis is not a common finding in papillary carcinoma. 18F-FDG can
      detect foci of metastasis in patients with negative 131I scan. We report a case
      of a 64-year-old man who had undergone thyroidectomy and 131I ablation due to
      classic type of papillary carcinoma 14 years ago. Follow-up examination revealed
      high serum thyroglobulin and negative whole body 131I scan. 18F-FDG PET/CT showed
      focally increased uptake in right axillary as well as supraclavicular and
      bilateral cervical lymph nodes. Histopathological examination of the surgically
      removed lymph nodes confirmed the metastasis of papillary thyroid carcinoma.

PMID- 22996246
TI  - The importance of Tc-MAA SPECT/CT for therapy planning of radioembolization in a
      patient treated with bevacizumab.
AB  - A 76-year-old man with colorectal cancer and hepatic metastases was referred to
      us for radioembolization of the liver. Angiography with 99mTc-MAA SPECT/CT was
      performed 8 weeks after the discontinuation of bevacizumab. 99mTc-MAA SPECT/CT
      showed a diffused intrahepatic tracer distribution with no focally accentuated
      accumulation in the tumorous region. The test was repeated 6 weeks later and Tc
      MAA SPECT/CT showed this time a tumor accentuated tracer accumulation in the
      liver. Subsequently, the patient was treated with resin microspheres. Tc-MAA
      SPECT/CT allows a better evaluation of intrahepatic tracer accumulation of Tc-MAA
      and facilitates the determination of the most appropriate treatment time.

PMID- 22996247
TI  - Dual-tracer PET/CT in renal angiomyolipoma and subtypes of renal cell carcinoma.
AB  - We studied the metabolic characteristics of RCC subtypes and angiomyolipoma with
      18F-FDG and 11C-acetate PET/CT. METHODS: Fifty-eight patients with both baseline
      CT and dual-tracer PET/CT were recruited: 10 angiomyolipoma (16 lesions) and 48
      RCC (50 lesions). Each lesion was assessed for SUVmax ratio (lesion-to-normal
      kidney) on 11C-acetate/18F-FDG PET and attenuation density on CT. Receiver
      operating characteristic (ROC) curve was analyzed to define the threshold of 11C
      acetate SUVmax ratio for differentiating angiomyolipoma from RCC. Thirty-nine RCC
      patients were selected for 3-year disease-free survival analysis. RESULTS: All
      angiomyolipoma showed negative 18F-FDG but markedly increased 11C-acetate
      metabolism, significantly higher than RCC (11C-acetate SUVmax ratio = 4.11 +/-
      0.53 vs 2.00 +/- 0.71; P < 0.05). 11C-acetate SUVmax ratio = 3.71 could
      differentiate angiomyolipoma including "fat-poor angiomyolipoma" (n = 10) from
      RCC with sensitivity of 93.8% (15/16) and specificity of 98.0% (49/50). Different
      RCC subtypes/grades (25 low- and 11 high-grade clear cell [CC], 7 chromophobe, 4
      papillary, and 1 collecting duct) were found to have different dual-tracer
      metabolic pattern (P < 0.05), with overall RCC detection sensitivity of 90%
      (45/50). All chromophobe RCC were avid only for C-acetate but not 18F-FDG,
      whereas papillary RCC were primarily the opposite. RCC-CC showed variable dual
      tracer uptake: high-grade more avid for F-FDG, low-grade more for 11C-acetate.
      Four RCC cases negative by dual-tracers were of low-grade RCC-CC. "Primary RCC
      being 18F-FDG-avid" was the only independent predictor of RCC recurrence in 3
      years (P < 0.05), with a median disease-free survival of 22 months. CONCLUSION:
      11C-acetate PET/CT helps in differentiating "fat-poor angiomyolipoma" from RCC.
      Dual-tracer PET/CT has value in diagnosis of RCC subtypes and predicting
      survival.

PMID- 22996248
TI  - Neurolymphomatosis diagnosed by (18)F-FDG PET-CT.
AB  - Neurolymphomatosis is defined as infiltration of the nervous system by
      hematological malignancy and is difficult to diagnose. We report a case of a 57
      year-old man, treated for small B-cell non-Hodgkin lymphoma, presenting with
      sensorimotor impairment of the lower limbs, which started 6 years after
      diagnosis. He was treated with chemotherapy, after which, the symptoms
      disappeared. After 7 months, he developed sensorimotor impairment of both upper
      limbs. MRI of the brachial plexus showed no abnormalities. F-FDG PET-CT showed
      increased uptake at the brachial plexus and nerves, suggesting
      neurolymphomatosis. Confirmatory biopsy revealed conversion of the malignancy to
      diffuse large B-cell lymphoma.

PMID- 22996249
TI  - The 18F-FDG PET/CT finding of a condyloma acuminata mimicking primary anorectal
      carcinoma in an HIV-infected patient.
AB  - This case report describes a condyloma acuminata with intense FDG uptake
      mimicking primary anorectal carcinoma in an HIV-infected patient.A 44-year-old
      HIV-positive homosexual man with a history of lymphoma underwent an 18F-FDG
      PET/CT for restaging. A focal intense hypermetabolic lesion around the anorectal
      area was found by the PET/CT and it was suggested as a tumorous lesion. However,
      the lesion was not detected on the contrast-enhanced abdominal CT. Via a
      sigmoidoscopy, cauliflower-like masses were visualized in the intra-anal area.
      The tumor was surgically excised and proven to be condyloma acuminata by
      permanent pathology.

PMID- 22996250
TI  - MRI and FDG PET/CT findings of hepatic epithelioid hemangioendothelioma.
AB  - PURPOSE: The aim of this study was to evaluate retrospectively magnetic resonance
      imaging (MRI) and (18)F fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG PET/CT) findings of hepatic epithelioid hemangioendothelioma
      (HEH). PATIENTS AND METHODS: MRI and FDG PET/CT findings were reviewed in 6
      patients with HEH confirmed by pathology. All patients underwent magnetic
      resonance (MR) examination. Early PET/CT scans were performed 1 hour after FDG
      injection in all 6 patients. After an interval of 1 hour, delayed PET/CT scans
      were performed in 4 patients. RESULTS: A total of 60 lesions were detected in all
      6 patients. MRI features of HEH included multifocal hepatic disease,
      predominantly subcapsular location, coalescence of lesions, and capsular
      retraction. T2-weighted MR images frequently showed a target-like configuration
      of the lesions. Contrast-enhanced MR images showed variable degrees of peripheral
      rim enhancement with delayed central enhancement. Forty lesions (67%) with
      increased FDG uptake and 20 lesions (33%) with FDG uptake similar to the
      surrounding liver parenchyma were found in all 6 patients. The mean maximum
      standardized uptake value (SUV(max)) of all lesions was 3.6 +/- 1.1, with a low
      variability of SUV(max) among lesions ranging from 1.7 to 6.6. There was no
      relationship between lesion sizes and corresponding SUV(max). Some larger lesions
      demonstrated a hypermetabolic peripheral rim reflecting hypercellular tumor
      regions and a relatively hypometabolic central area corresponding to hypocellular
      stroma. Eleven lesions with increased FDG uptake on the delayed PET/CT images
      were found in 3 patients, and 19 lesions with decreased FDG uptake were found in
      all 4 patients with total 32 lesions. CONCLUSIONS: MRI demonstrated morphological
      features of HEH and FDG PET/CT reflected the histopathological composition of the
      tumors. FDG uptake of HEH may be related to tumor cellularity, but not the tumor
      size. Dual-time-point imaging may be not useful for differentiating benign
      lesions from HEH. Familiarity with the morphological and functional imaging
      findings of HEH is useful for recognition of this rare hepatic tumor.

PMID- 22996251
TI  - Tips for giving a memorable presentation Part V: stage fright and rehearsing a
      presentation.
AB  - Previous articles in this series have included many tips on composing a memorable
      presentation. This article will focus on rehearsing the presentation and dealing
      with stage fright. There are additional comments on making sure everything is
      optimized in the lecture room in advance and other tips for the actual
      presentation.

PMID- 22996252
TI  - 68Ga-DOTATATE-PET/CT positive metastatic lymph node in a 69-year-old woman with
      Merkel cell carcinoma.
AB  - We report the case of a 69-year-old woman with a Merkel cell carcinoma (MCC) in
      whom subsequent lymph node metastasis was first diagnosed by 68Ga-Dotatate-PET/CT
      followed by histopathological confirmation. MCC is an extraordinarily rare and
      aggressive neuroendocrine tumor of dermal origin with a high rate of
      postoperative recurrence. Owing to its rarity, the diagnosis of MCC remains a
      significant challenge. In our case, 68Ga-Dotatate-PET/CT proved clinically useful
      for diagnosing the lymph node metastasis of a MCC.

PMID- 22996253
TI  - Combination of initial stimulation thyroglobulins and staging system by revised
      ATA guidelines can elaborately discriminate prognosis of patients with
      differentiated thyroid carcinoma after high-dose remnant ablation.
AB  - PURPOSE: The aim of this study was to evaluate prognostic role of thyroglobulin
      (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12
      months after remnant ablation (S-Tg) combined with revised American Thyroid
      Association (ATA) guidelines risk stratification. PATIENTS AND METHODS: Data of
      359 patients (median follow-up duration: 66.3 months) with papillary thyroid
      carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A
      Tg to predict the persistent/recurrent disease was calculated by receiver
      operating characteristic curve analysis. In each risk group by ATA guidelines,
      the association of A-Tg with persistent/recurrent disease was evaluated. The role
      of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL,
      2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the
      difference between A-Tg and S-Tg with consideration of the dose of radioactive
      iodine ablation. RESULTS: A-Tg above 5.22 ng/mL was associated with
      persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the
      cutoff value and ATA risk assessment was related to persistent/recurrent disease
      in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P =
      0.019). However, no difference in the incidence of persistent/recurrent disease
      was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and
      ATA staging showed elaborate discrimination of prognosis. CONCLUSION: Risk
      stratification using combined scoring with initial stimulated Tg levels,
      including A-Tg and S-Tg, and staging system by revised ATA guidelines can
      effectively predict persistent/recurrent disease in patients with papillary
      thyroid carcinoma.

PMID- 22996255
TI  - Self-regulated supramolecular assembly driven by a chemical-oscillating reaction.
AB  - A novel self-regulated supramolecular assembly (SSA) system driven by a chemical
      oscillating reaction is constructed based on dynamic supramolecular interactions
      and the rhythm of the SSA process can be controlled by temperature.

PMID- 22996254
TI  - "Quasi-symmetric" FDG avidity of bilateral salivary glands in Mikulicz disease
      yielding false-positive staging in lung cancer.
AB  - A 77-year-old man with lung cancer underwent fluorodeoxyglucose (FDG) positron
      emission tomography/computed tomography (PET/CT). Cervical FDG uptake of variable
      intensity was detected corresponding to enlarged masses in the bilateral parotid
      and left submandibular regions. We suspected metastases from primary lung cancer
      or coexisting salivary gland neoplasms. Histopathological examination of the FDG
      avid parotid mass revealed Mikulicz disease, an uncommon autoimmune disease
      involving the salivary glands. We present this case of Mikulicz disease with
      "quasi-symmetric" FDG avidity in the major salivary glands. We believe that
      salivary FDG uptake can lead to erroneous interpretation of tumor staging using
      PET.

PMID- 22996256
TI  - Partial atomic charges and their impact on the free energy of solvation.
AB  - Free energies of solvation (DeltaG) in water and n-octanol have been computed for
      common drug molecules by molecular dynamics simulations with an additive fixed
      charge force field. The impact of the electrostatic interactions was investigated
      by computing the partial atomic charges with four methods that all fit the
      charges from the quantum mechanically determined electrostatic potential (ESP).
      Due to the redistribution of electron density that occurs when molecules are
      transferred from gas phase to condensed phase, the polarization impact was also
      investigated. By computing the partial atomic charges with the solutes placed in
      a conductor-like continuum, the charges were effectively polarized to take the
      polarization effects into account. No polarization correction term or similar was
      considered, only the partial atomic charges. Results show that free energies are
      very sensitive to the choice of atomic charges and that DeltaG can differ by
      several k(B)T depending on the charge computing method. Inclusion of polarization
      effects makes the solutes too hydrophilic with most methods and in vacuo charges
      make the solutes too hydrophobic. The restrained-ESP methods together with
      effectively polarized charges perform well in our test set and also when applied
      to a larger set of molecules. The effect of water models is also highlighted and
      shows that the conclusions drawn are valid for different three-point models.
      Partitioning between an aqueous and a hydrophobic phase is also described better
      if the two environment's polarization is taken into account, but again the
      results are sensitive to the charge calculation method. Overall, the results
      presented here show that effectively polarized charges can improve the
      description of solvating a drug-like molecule in a solvent and that the choice of
      partial atomic charges is crucial to ensure that molecular simulations produce
      reliable results.

PMID- 22996257
TI  - Trichomes as models for studying plant cell differentiation.
AB  - Trichomes, originating from epidermal cells, are present on nearly all
      terrestrial plants. They exist in diverse forms, are readily accessible, and
      serve as an excellent model system for analyzing the molecular mechanisms in
      plant cell differentiation, including cell fate choices, cell cycle control, and
      cell morphogenesis. In Arabidopsis, two regulatory models have been identified
      that function in parallel in trichome formation; the activator-inhibitor model
      and the activator-depletion model. Cotton fiber, a similar unicellular structure,
      is controlled by some functional homologues of Arabidopsis trichome-patterning
      genes. Multicellular trichomes, as in tobacco and tomato, may form through a
      distinct pathway from unicellular trichomes. Recent research has shown that cell
      cycle control participates in trichome formation. In this review, we summarize
      the molecular mechanisms involved in the formation of unicellular and
      multicellular trichomes, and discuss the integration of the cell cycle in its
      initiation and morphogenesis.

PMID- 22996259
TI  - Pickering emulsion stabilized by catalytic polyoxometalate nanoparticles: a new
      effective medium for oxidation reactions.
AB  - Decyl-, dodecyl-, and tetradecyltrimethylammonium cations were combined with the
      catalytic polyoxometalate [PW(12)O(40)](3-) anion to give spherical and
      monodisperse nanoparticles that are able to stabilize emulsions in the presence
      of water and an aromatic solvent. This triphasic liquid/solid/liquid system,
      based on a catalytic surfactant, is particularly efficient as a reaction medium
      for epoxidation reactions that involve hydrogen peroxide. The reactions proceed
      at competitive rates with straightforward separation of the phases by
      centrifugation. Such catalytic "Pickering" emulsions combine the advantages of
      heterogeneous catalysis and biphasic catalysis without the drawbacks (e.g.,
      catalyst leaching or separation time).

PMID- 22996258
TI  - Molecular mechanisms of desiccation tolerance in the resurrection glacial relic
      Haberlea rhodopensis.
AB  - Haberlea rhodopensis is a resurrection plant with remarkable tolerance to
      desiccation. Haberlea exposed to drought stress, desiccation, and subsequent
      rehydration showed no signs of damage or severe oxidative stress compared to
      untreated control plants. Transcriptome analysis by next-generation sequencing
      revealed a drought-induced reprogramming, which redirected resources from growth
      towards cell protection. Repression of photosynthetic and growth-related genes
      during water deficiency was concomitant with induction of transcription factors
      (members of the NAC, NF-YA, MADS box, HSF, GRAS, and WRKY families) presumably
      acting as master switches of the genetic reprogramming, as well as with an
      upregulation of genes related to sugar metabolism, signaling, and genes encoding
      early light-inducible (ELIP), late embryogenesis abundant (LEA), and heat shock
      (HSP) proteins. At the same time, genes encoding other LEA, HSP, and stress
      protective proteins were constitutively expressed at high levels even in
      unstressed controls. Genes normally involved in tolerance to salinity, chilling,
      and pathogens were also highly induced, suggesting a possible cross-tolerance
      against a number of abiotic and biotic stress factors. A notable percentage of
      the genes highly regulated in dehydration and subsequent rehydration were novel,
      with no sequence homology to genes from other plant genomes. Additionally, an
      extensive antioxidant gene network was identified with several gene families
      possessing a greater number of antioxidant genes than most other species with
      sequenced genomes. Two of the transcripts most abundant during all conditions
      encoded catalases and five more catalases were induced in water-deficient
      samples. Using the pharmacological inhibitor 3-aminotriazole (AT) to compromise
      catalase activity resulted in increased sensitivity to desiccation. Metabolome
      analysis by GC or LC-MS revealed accumulation of sucrose, verbascose, spermidine,
      and gamma-aminobutyric acid during drought, as well as particular secondary
      metabolites accumulating during rehydration. This observation, together with the
      complex antioxidant system and the constitutive expression of stress protective
      genes suggests that both constitutive and inducible mechanisms contribute to the
      extreme desiccation tolerance of H. rhodopensis.

PMID- 22996260
TI  - Successful transplantation of human hepatic stem cells with restricted
      localization to liver using hyaluronan grafts.
AB  - Cell therapies are potential alternatives to organ transplantation for liver
      failure or dysfunction but are compromised by inefficient engraftment, cell
      dispersal to ectopic sites, and emboli formation. Grafting strategies have been
      devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a
      mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type
      III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable
      stem cell phenotype under the graft conditions. The grafts were transplanted into
      the livers of immunocompromised murine hosts with and without carbon
      tetrachloride treatment to assess the effects of quiescent versus injured liver
      conditions. Grafted cells remained localized to the livers, resulting in a larger
      bolus of engrafted cells in the host livers under quiescent conditions and with
      potential for more rapid expansion under injured liver conditions. By contrast,
      transplantation by direct injection or via a vascular route resulted in
      inefficient engraftment and cell dispersal to ectopic sites. Transplantation by
      grafting is proposed as a preferred strategy for cell therapies for solid organs
      such as the liver.

PMID- 22996262
TI  - Endosalpingiosis can mimic malignant glands and result in a false positive
      mesorectal resection margin.

PMID- 22996261
TI  - Evidence for substrate-dependent inhibition profiles for human liver aldehyde
      oxidase.
AB  - The goal of this study was to provide a reasonable assessment of how probe
      substrate selection may impact the results of in vitro aldehyde oxidase (AO)
      inhibition experiments. Here, we used a previously studied set of seven known AO
      inhibitors to probe the inhibition profile of a pharmacologically relevant
      substrate N-[(2-dimethylamino)ethyl]acridine-4-carboxamide (DACA). DACA oxidation
      in human liver cytosol was characterized with a measured V(max) of 2.3 +/- 0.08
      nmol product . min(-1) . mg(-1) and a K(m) of 6.3 +/- 0.8 uM. The K(ii) and K(is)
      values describing the inhibition of DACA oxidation by the panel of seven
      inhibitors were tabulated and compared with previous findings with phthalazine as
      the substrate. In every case, the inhibition profile shifted to a much less
      uncompetitive mode of inhibition for DACA relative to phthalazine. With the
      exception of one inhibitor, raloxifene, this change in inhibition profile seems
      to be a result of a decrease in the uncompetitive mode of inhibition (an affected
      K(ii) value), whereas the competitive mode (K(is)) seems to be relatively
      consistent between substrates. Raloxifene was found to inhibit competitively when
      using DACA as a probe, and a previous report showed that raloxifene inhibited
      uncompetitively with other substrates. The relevance of these data to the
      mechanistic understanding of aldehyde oxidase inhibition and potential
      implications on drug-drug interactions is discussed. Overall, it appears that the
      choice in substrate may be critical when conducting mechanistic inhibition or in
      vitro drug-drug interactions prediction studies with AO.

PMID- 22996263
TI  - Surgical results of long posterior fixation with short fusion in the treatment of
      pyogenic spondylodiscitis of the thoracic and lumbar spine: a retrospective
      study.
AB  - STUDY DESIGN: A single-institution, single-surgeon retrospective review.
      OBJECTIVE: To evaluate the clinical results of long posterior instrumentation
      with short posterior or posterolateral fusion for pyogenic spondylodiscitis of
      the thoracic and lumbar spine retrospectively. SUMMARY OF BACKGROUND DATA: There
      are controversies concerning the optimal treatment for pyogenic spondylodiscitis,
      in terms of approach, grafting, and instrumentation. Reports of long posterior
      fixation with short fusion without debridement of infected tissue for pyogenic
      spondylodiscitis are rare. METHODS: From June 1997 to June 2007, 48 patients with
      pyogenic spondylodiscitis were treated. The indications for surgery were
      neurological compromise, significant vertebral body destruction with kyphosis and
      segmental instability, failure of medical treatment, and the need for tissue
      diagnosis. All patients received long posterior instrumentation with or without
      posterior decompression, depending on whether the patients had neurological
      deficit. During operation, no debridement of infected tissue was done. Clinical
      outcomes were assessed using the criteria of Kirkaldy-Willis and the visual
      analogue scale for pain. The neurological outcome was graded using Frankel
      grading system. Segmental kyphotic angle and fusion were recorded and analyzed.
      RESULTS: The average follow-up time was 64 months. The visual analogue scale
      scores improved from an average of 7.2 before surgery to 2.2 after surgery.
      Twenty-eight patients with initial neurological impairment had an average
      improvement of 1.03 grades, using the Frankel grading system, at the final follow
      up. The segmental kyphotic deformity improved by an average of 8.5 degrees 
      immediately after operation and lost an average correction of 3.0 degrees  at the
      final follow-up. No relapse of infection was found among these 48 patients.
      CONCLUSION: The posterior approach with long segmental fixation and short
      posterior or posterolateral fusion without debridement of the infected tissue was
      effective for pyogenic spondylodiscitis of the thoracic and lumbar spine.

PMID- 22996264
TI  - Pedicle screw design and cement augmentation in osteoporotic vertebrae: effects
      of fenestrations and cement viscosity on fixation and extraction.
AB  - STUDY DESIGN: Experimental, human cadaveric study. OBJECTIVE: To assess the
      fixation effects of injecting cement augmentation before screw insertion or after
      insertion of fenestrated screws; the effect of modulating cement viscosity; and
      the effects of these techniques on screw removal. SUMMARY OF BACKGROUND DATA: It
      seems clear that cement augmentation can enhance pedicle screw fixation in
      osteoporotic bone. What remains to be demonstrated is the aspects of optimal
      technique such that fixation is enhanced with the greatest safety profile.
      METHODS: Part I: Human osteoporotic vertebrae were instrumented with solid
      (nonaugmented) screws, solid screws with polymethylmethacrylate (PMMA), partially
      cannulated fenestrated (Pfen) screws, or fully cannulated fenestrated (Ffen)
      screws through which PMMA was injected. Screw fixation was tested in pullout.
      Part II: Ffen screws were augmented with standard low-viscosity PMMA versus high
      viscosity PMMA. Part III: Sample cohorts were extracted from vertebrae to assess
      required torque and characterize difficulty of extraction. RESULTS: Part I: Pfen
      screws demonstrated the greatest fixation with mean failure force of 690 +/- 182
      N. All methods of cement augmentation demonstrated significant increases in screw
      fixation. Part II: Ffen screws did not demonstrate a significant difference in
      pullout strength when high-viscosity PMMA was used as compared with low-viscosity
      PMMA. Part III: Mean extraction torque values for solid augmented screws, Ffen
      screws, and Pfen screws were 1.167, 1.764, and 1.794 Nm, respectively, but these
      differences did not reach significance. None of the osteoporotic vertebrae
      sustained catastrophic failure during augmented screw extraction. CONCLUSION:
      Polymethylmethacrylate cement augmentation clearly enhances pedicle screw
      fixation in osteoporotic vertebrae when tested in pure pullout. The technique
      used for cement injection and choice of specialty screws can have a significant
      impact on the magnitude of this effect. Fenestrated screws have the capacity to
      confine cement placement in the vertebral body and may provide enhanced safety
      from cement extrusion into the spinal canal. It is feasible to inject high
      viscosity PMMA through this fenestration geometry, and higher-viscosity cement
      may enhance the fixation effect.

PMID- 22996265
TI  - The relationship between the anatomy of the nuchal ligament and postoperative
      axial pain after cervical laminoplasty: cadaver and clinical study.
AB  - STUDY DESIGN: A cadaver and clinical study investigated the attachment of the
      nuchal ligament to the cervical spinous process. OBJECTIVE: To investigate the
      anatomical details of the attachment of the nuchal ligament to the spinous
      process and the relationship between the morphology of the nuchal ligament and
      postoperative axial pain after laminoplasty. SUMMARY OF BACKGROUND DATA: The
      relationship between the length of the C6 spinous process and the morphology of
      the nuchal ligament and occurrence of postoperative axial pain has not been
      elucidated. METHODS: The morphology of the nuchal ligament was investigated in 35
      cadavers and 60 patients on preoperative computed tomography and magnetic
      resonance imaging. The lengths of the C6 and C7 spinous processes were measured,
      and the C6:C7 ratio (C6 spinous process length/C7 spinous process length) was
      calculated. The relationship between the morphology of the attachment of nuchal
      ligament to the C6 spinous process and the C6:C7 ratio were investigated. In
      addition, the effects of the anatomy of the nuchal ligament around the C6 spinous
      process and different procedures of surgical invasion to C6 or C7 on
      postoperative axial pain were investigated for 113 patients who underwent
      laminoplasty. RESULTS: The nuchal ligament was attached to not only the C7
      spinous process, but also the C6 spinous process when the C6:C7 ratio was more
      than 0.8. When the nuchal ligament was attached to the C6 spinous process and to
      C7, postoperative axial pain after C3-C7 laminoplasty occurred more often
      compared with C3-C6 laminoplasty for patients without the nuchal ligament
      attached to the C6 spinous process. CONCLUSION: This study shows that there is an
      association between the individual anatomical differences of the nuchal ligament
      and the occurrence of postoperative axial pain after laminoplasty. Careful
      attention should be paid to the morphology of the attachment of the nuchal
      ligament to the C6 spinous process to reduce postoperative axial pain.

PMID- 22996266
TI  - Analysis of the risk factors for tracheostomy in traumatic cervical spinal cord
      injury.
AB  - STUDY DESIGN: A retrospective, consecutive case series. OBJECTIVE: To determine
      the risk factors that have a statistically significant association with the need
      of tracheostomy in patients with cervical spinal cord injury (CSCI) at the acute
      stage. SUMMARY OF BACKGROUND DATA: Respiratory complications remain a major cause
      of further morbidity and mortality in patients with CSCI. Although several risk
      factors for tracheostomy have been postulated in these patients, no definitive
      factors have yet been established according to a multivariate analysis. The use
      of vital capacity was considered as a single global measure of respiratory
      function in patients with spinal cord injury, but there are very few studies in
      which the forced vital capacity was investigated as a risk factor for
      tracheostomy. METHODS: This study that reviewed the clinical data of 319 patients
      with CSCI, who were evaluated for their neurological impairment within 2 days
      after injury, was performed. We analyzed the factors postulated to increase the
      risk for tracheostomy, including patient's age, neurological impairment scale
      grade and level, smoking history, pre-existing medical comorbidities, respiratory
      diseases, Injury Severity Score, forced vital capacity, and percentage of vital
      capacity to the predicted value (%VC), using a multiple logistic regression model
      and classification and regression tree analysis. RESULTS: Of 319 patients, 32
      patients received tracheostomy (10.03%). The factors identified using a multiple
      logistic regression model were high age (69 years of age or older), severe
      neurological impairment scale, low forced vital capacity (<= 500 mL), and low
      percentage of vital capacity to the predicted value (<16.3%). The decision tree
      analysis demonstrated that forced vital capacity, the severe neurological
      impairment scale, and high patient age were predictive of need for tracheostomy
      on 94.4% occasions. CONCLUSION: The measurement of forced vital capacity is
      indispensable to predict the need for tracheostomy in patients with CSCI at the
      acute stage.

PMID- 22996267
TI  - Serum titanium, niobium, and aluminum levels after instrumented spinal
      arthrodesis in children.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: To determine serum titanium,
      niobium, and aluminum levels in pediatric patients within the first postoperative
      year after instrumented spinal arthrodesis. SUMMARY OF BACKGROUND DATA:
      Instrumented spinal arthrodesis is a common procedure to correct scoliosis and
      kyphosis. Titanium-based instrumentation is increasingly favored due to enhanced
      biomechanical properties, but concerns have arisen regarding metal debris release
      and the potential for local and systemic complications. METHODS: The pattern of
      systemic metal release over time was evaluated by measuring serum titanium,
      niobium, and aluminum levels preoperatively and 1 week, 1 month, 6 months, and 12
      months after instrumented spinal arthrodesis using a titanium alloy. Serum metal
      levels were measured using high-resolution inductively coupled plasma mass
      spectrometry. RESULTS: Thirty-two patients were included in the study group. Mean
      age at surgery was 14.7 years. Preoperative and postoperative concentrations of
      serum titanium and niobium were significantly different (P = 0.0001). Median
      postoperative serum concentrations of titanium and niobium were elevated 2.4- and
      5.9-fold above the normal range respectively with 95% and 99% of samples elevated
      postoperatively. A significant and rapid rise in serum titanium and niobium
      levels was observed within the first postoperative week, after which elevated
      serum levels persisted up to 12 months. CONCLUSION: We report abnormally elevated
      serum titanium and niobium levels in patients with titanium-based spinal
      instrumentation up to 12 months. The long-term systemic consequences of debris
      generated by wear and corrosion of spinal instrumentation is unclear but
      concerning, particularly as these implants inserted into the pediatric population
      may remain in situ for beyond 6 decades.

PMID- 22996268
TI  - Total disc replacement for chronic discogenic low back pain: a Cochrane review.
AB  - STUDY DESIGN: Systematic literature review. OBJECTIVE: To assess the effect of
      total disc replacement for chronic low back pain due to lumbar degenerative disc
      disease compared with fusion or other treatment options. SUMMARY OF BACKGROUND
      DATA: There is an increasing use in disc replacement devices for degenerative
      disc disease, but their effectiveness compared with other interventions such as
      fusion of the motion segment or conservative treatment remains unclear. METHODS:
      A comprehensive search in PubMedCentral, MEDLINE, EMBASE, BIOSIS,
      ClinicalTrials.gov, and FDA trials register was conducted. Randomized controlled
      trials comparing total disc replacement with any other intervention for
      degenerative disc disease were included. Risk of bias was assessed using the
      criteria of the Cochrane Back Review Group. Quality of evidence was graded
      according to the GRADE approach. Two review authors independently selected
      studies, assessed risk of bias, and extracted data. Results and upper bounds of
      confidence intervals were compared with predefined clinically relevant
      differences. RESULTS: We included 7 randomized controlled trials with a follow-up
      of 24 months. There is risk of bias in the included studies due to sponsoring and
      absence of any kind of blinding. One study compared disc replacement with
      rehabilitation and found a significant advantage in favor of surgery, which,
      however, did not reach the predefined threshold. Six studies compared disc
      replacement with fusion and found that the mean improvement in visual analogue
      scale score of back pain was 5.2 mm higher (2 studies; 95% confidence interval
      0.2-10.3) with a low quality of evidence. The improvement of Oswestry disability
      index score at 24 months in the disc replacement group was 4.3 points more than
      in the fusion group (5 studies; 95% confidence interval 1.85-6.68) with a low
      quality of evidence. Both upper bounds of the confidence intervals were below the
      predefined clinically relevant difference. CONCLUSION: Although statistically
      significant, the differences in clinical improvement were not beyond generally
      accepted boundaries for clinical relevance. Prevention of adjacent level disease
      and/or facet joint degeneration was not properly assessed. Therefore, because we
      think that harm and complications may occur after some years, the spine surgery
      community should be prudent to adopt this technology on a large scale, despite
      the fact that total disc replacement seems to be effective in treating low back
      pain in selected patients, and in the short term is at least equivalent to fusion
      surgery.

PMID- 22996269
TI  - A novel mutation in the complement component 3 gene in a patient with selective
      IgA deficiency.
AB  - PURPOSE: Immunological and molecular evaluation of a patient presenting with
      recurrent infections caused by Streptococcus pneumoniae and low complement
      component 3 (C3) levels. METHODS: Immunological evaluation included complement
      components and immunoglobulin level quantification as well as number and function
      of T cells, B cells and neutrophils. Serotype-specific immunoglobulin G
      antibodies against S. pneumoniae capsular polysaccharides were quantified by
      ELISA in serum samples before and after vaccination with unconjugated
      polysaccharide vaccine. For the molecular analysis, genomic DNA from the patient
      and parents were isolated and all exons as well as exon-intron boundaries of the
      C3 gene were sequenced by Sanger sequencing. RESULTS: A 16-year-old male, born to
      consanguineous parents, presented with recurrent episodes of pneumonia caused by
      S. pneumoniae and bronchiectasis. The patient showed severely reduced C3 and
      immunoglobulin A levels, while the parents showed moderately reduced levels of
      C3. Mutational analysis revealed a novel, homozygous missense mutation in the C3
      gene (c. C4554G, p. Cys1518Trp), substituting a highly conserved amino acid in
      the C345C domain of C3 and interrupting one of its disulfide bonds. Both parents
      were found to be carriers of the affected allele. Vaccination against S.
      pneumoniae resulted in considerable clinical improvement. CONCLUSIONS: We report
      a novel homozygous mutation in the C3 gene in a patient with concomitant
      selective IgA deficiency who presented with a marked clinical improvement after
      vaccination against S. pneumoniae. This observation underlines the notion that
      vaccination against this microorganism is an important strategy for treatment of
      PID patients, particularly those presenting with increased susceptibility to
      infections caused by this agent.

PMID- 22996270
TI  - Enhancement of membrane B7-H3 costimulatory molecule but reduction of its soluble
      form in multiple sclerosis.
AB  - PURPOSE: Multiple sclerosis (MS) is an autoimmune disease of the central nervous
      system mediated by T cells. B7-H3 plays a diverse role in regulating T cell
      responses. However, its expression and clinical significance in MS are not well
      known. This study analyzed the expression of membrane B7-H3 (mB7-H3) and levels
      of soluble B7-H3 (sB7-H3) in MS patients to determine its clinical significance.
      METHODS: Peripheral blood (PB) or cerebrospinal fluid (CSF) samples from healthy
      controls, other noninflammatory neurological disorders, viral encephalitis, and
      MS patients were collected. Expression of mB7-H3 on immune cells was detected by
      flow cytometry. Levels of sB7-H3 in serum or CSF samples were measured by ELISA.
      RESULTS: mB7-H3 expression was up-regulated in CSF from MS patients compared to
      PB (p<0.001). However, serum or CSF levels of sB7-H3 in MS patients were
      significantly lower than those in controls (p<0.05). Relapsing-MS patients had
      higher CSF mB7-H3 expression than the remitting subgroup. Relapsing-MS patients
      had decreased serum and CSF sB7-H3 levels compared with the remitting subgroup.
      Neurological deficits showed negative correlations with serum or CSF sB7-H3
      levels, but a positive correlation with CSF mB7-H3 expression. Methylprednisolone
      therapy significantly elevated sB7-H3 levels and reduced mB7-H3 expression
      compared with pre-therapy levels. sB7-H3 levels did not correlate with mB7-H3
      expression. CONCLUSIONS: We demonstrated enhanced mB7-H3 expression and reduced
      sB7-H3 levels in MS patients which correlated with the clinical characteristics
      of MS patients. These results suggest that B7-H3 may be a promising biomarker and
      associated with the pathogenesis of MS.

PMID- 22996271
TI  - Progress toward understanding the contribution of alkali generation in dental
      biofilms to inhibition of dental caries.
AB  - Alkali production by oral bacteria is believed to have a major impact on oral
      microbial ecology and to be inhibitory to the initiation and progression of
      dental caries. A substantial body of evidence is beginning to accumulate that
      indicates the modulation of the alkalinogenic potential of dental biofilms may be
      a promising strategy for caries control. This brief review highlights recent
      progress toward understanding molecular genetic and physiologic aspects of
      important alkali-generating pathways in oral bacteria, and the role of alkali
      production in the ecology of dental biofilms in health and disease.

PMID- 22996272
TI  - A post-classical theory of enamel biomineralization... and why we need one.
AB  - Enamel crystals are unique in shape, orientation and organization. They are
      hundreds of thousands times longer than they are wide, run parallel to each
      other, are oriented with respect to the ameloblast membrane at the mineralization
      front and are organized into rod or interrod enamel. The classical theory of
      amelogenesis postulates that extracellular matrix proteins shape crystallites by
      specifically inhibiting ion deposition on the crystal sides, orient them by
      binding multiple crystallites and establish higher levels of crystal
      organization. Elements of the classical theory are supported in principle by in
      vitro studies; however, the classical theory does not explain how enamel forms in
      vivo. In this review, we describe how amelogenesis is highly integrated with
      ameloblast cell activities and how the shape, orientation and organization of
      enamel mineral ribbons are established by a mineralization front apparatus along
      the secretory surface of the ameloblast cell membrane.

PMID- 22996273
TI  - Methods for studying tooth root cementum by light microscopy.
AB  - The tooth root cementum is a thin, mineralized tissue covering the root dentin
      that is present primarily as acellular cementum on the cervical root and cellular
      cementum covering the apical root. While cementum shares many properties in
      common with bone and dentin, it is a unique mineralized tissue and acellular
      cementum is critical for attachment of the tooth to the surrounding periodontal
      ligament (PDL). Resources for methodologies for hard tissues often overlook
      cementum and approaches that may be of value for studying this tissue. To address
      this issue, this report offers detailed methodology, as well as comparisons of
      several histological and immunohistochemical stains available for imaging the
      cementum-PDL complex by light microscopy. Notably, the infrequently used Alcian
      blue stain with nuclear fast red counterstain provided utility in imaging
      cementum in mouse, porcine and human teeth. While no truly unique extracellular
      matrix markers have been identified to differentiate cementum from the other hard
      tissues, immunohistochemistry for detection of bone sialoprotein (BSP),
      osteopontin (OPN), and dentin matrix protein 1 (DMP1) is a reliable approach for
      studying both acellular and cellular cementum and providing insight into
      developmental biology of these tissues. Histological and immunohistochemical
      approaches provide insight on developmental biology of cementum.

PMID- 22996274
TI  - Stereoselectivity in the salt-cocrystal products formed by phenylglycinol or
      phenylglycine with their respective sodium or hydrochloride salts.
AB  - The salt and stereoselective cocrystal phenomena associated with 2-phenylglycinol
      and 2-phenylglycine have been studied using X-ray powder diffraction and
      differential scanning calorimetry. The chiral identities of the free acids and
      their sodium salts, or the free bases and their chloride salts, were found to
      play a determining role as to whether a salt-cocrystal product could or could not
      be formed. In particular, when cocrystallization of an enantiomerically pure
      basic or zwitterionic substance with its enantiomerically pure acid addition salt
      was attempted, a salt-cocrystal was only obtained when the absolute configuration
      of the two reactants is opposite. On the other hand, it has been found that no
      stereoselectivity in salt-cocrystal formation existed in the cocrystallization of
      an enantiomerically pure acidic or zwitterionic substance with its
      enantiomerically pure base addition salt.

PMID- 22996275
TI  - Tetanus in Ethiopia: unveiling the blight of an entirely vaccine-preventable
      disease.
AB  - Today, tetanus exacts its toll only in resource-poor countries like Ethiopia.
      Agrarian rural life with limited vaccine typifies tetanus risk in Ethiopia where
      current tetanus control trends on expanding infant immunization and eliminating
      highly prevalent maternal and neonatal tetanus (MNT). Protection by infant
      tetanus immunization primers disappears within an average of 3 years, if not
      followed by boosters. Second-year of life, school-based, and universal 10-yearly
      tetanus immunizations need to be supplemented. Facility-based reviews in Ethiopia
      reveal a continued burden of tetanus at tertiary-level hospitals where ICU care
      is suboptimal. Quality of medical care for tetanus is low - reflected by high
      case-fatality-rates. Opportunities at primary-health-care-units (antenatal-care,
      family planning, abortion, wound-care, tetanus-survivors) need to be fully
      utilized to expand tetanus immunization. Prompt wound-care with post-exposure
      prophylaxis and proper footwear must be promoted. Standard ICU care needs to
      exist. Realization of cold-chain-flexible, needle-less and mono-dose vaccine
      programs allow avoiding boosters, vaccine-refrigeration, and improve compliance.

PMID- 22996276
TI  - Critical factors for the replication of mumps virus in primary chicken embryo
      fibroblasts defined by the use of design of experiments (DoE).
AB  - Live attenuated vaccines against mumps virus (MuV) have been traditionally
      produced by passaging the virus in the embryonated chicken eggs or primary
      chicken embryo fibroblasts (CEFs). Virus propagation on these cell substrates
      enables successful virus attenuation and retains it sufficiently antigenic to
      induce lasting protective immunity in humans. The aim of this study was to
      identify critical factors for MuV replication in primary CEFs grown on a small
      scale level in order to explore possibilities for improvements in the virus
      replication and yield. The effect of differently prepared cells, culturing
      conditions, and infection conditions on virus yield was estimated by employing
      statistical design of experiments (DoE) methodology. Our results show that the
      preparation of primary CEFs and the way of their infection substantially impact
      virus yield and are critical for efficient MuV replication. These process
      parameters should be considered in further process optimization. We also
      demonstrate the applicability of DoE in optimization of virus replication as a
      crucial step in obtaining high virus yields.

PMID- 22996277
TI  - Microalgal carbohydrates: an overview of the factors influencing carbohydrates
      production, and of main bioconversion technologies for production of biofuels.
AB  - Microalgal biomass seems to be a promising feedstock for biofuel generation.
      Microalgae have relative high photosynthetic efficiencies, high growth rates, and
      some species can thrive in brackish water or seawater and wastewater from the
      food- and agro-industrial sector. Today, the main interest in research is the
      cultivation of microalgae for lipids production to generate biodiesel. However,
      there are several other biological or thermochemical conversion technologies, in
      which microalgal biomass could be used as substrate. However, the high protein
      content or the low carbohydrate content of the majority of the microalgal species
      might be a constraint for their possible use in these technologies. Moreover, in
      the majority of biomass conversion technologies, carbohydrates are the main
      substrate for production of biofuels. Nevertheless, microalgae biomass
      composition could be manipulated by several cultivation techniques, such as
      nutrient starvation or other stressed environmental conditions, which cause the
      microalgae to accumulate carbohydrates. This paper attempts to give a general
      overview of techniques that can be used for increasing the microalgal biomass
      carbohydrate content. In addition, biomass conversion technologies, related to
      the conversion of carbohydrates into biofuels are discussed.

PMID- 22996278
TI  - Impact of dissolved hydrogen partial pressure on mixed culture fermentations.
AB  - Mixed culture fermentations are of interest for the low-cost production of
      organic acids from complex agricultural waste streams. Models are developed for
      these processes in order to predict the product spectrum as a function of the
      environmental process conditions. An important assumption in many existing models
      for anaerobic mixed culture fermentations is that the NADH/NAD(+) ratio is
      directly coupled to the dissolved hydrogen partial pressure (pH2, liquid). In
      this study, this assumption was tested experimentally with mixed culture
      chemostats operated at dilution rates of 0.05 and 0.125 h(-1) for a wide range of
      calculated dissolved hydrogen partial pressures (0.04-6.8 atm). No correlation
      was found between pH2, liquid and the NADH/NAD(+) ratio. This result, together
      with thermodynamic calculations, suggests that additional electron carriers such
      as ferredoxin and formate should be included in models predicting product
      formation by mixed cultures.

PMID- 22996279
TI  - Assimilation of aromatic compounds by Comamonas testosteroni: characterization
      and spreadability of protocatechuate 4,5-cleavage pathway in bacteria.
AB  - Comamonas testosteroni strain CNB-1 was isolated from activated sludge and has
      been investigated for its ability to degrade 4-chloronitrobenzene. Results from
      this study showed that strain CNB-1 grew on phenol, gentisate, vanillate, 3
      hydroxybenzoate (3HB), and 4-hydroxybenzoate (4HB) as carbon and energy sources.
      Proteomic data and enzyme activity assays suggested that vanillate, 3HB, and 4HB
      were degraded in strain CNB-1 via protocatechuate (PCA) 4,5-cleavage pathway. The
      genetics and biochemistry of the PCA 4,5-cleavage pathway were investigated.
      Results showed that the 4-oxalomesaconate (OMA) hydratase from C. testosteroni
      takes only enol-OMA as substrate. A previously functionally unknown gene pmdU
      encodes an OMA tautomerase and catalyzes conversion of OMAketo into OMAenol. The
      4-carboxy-4-hydroxy-2-oxoadipate (CHA) aldolase is encoded by pmdF and catalyzes
      the last step of the PCA 4,5-cleavage pathway. We explored the 1,183 microbial
      genomes at GenBank for potential PCA 4,5-cleavage pathways, and 33 putative pmd
      clusters were found. Results suggest that PCA 4,5-cleavage pathways are mainly
      distributed in alpha- and beta-Proteobacteria.

PMID- 22996280
TI  - Tuning the substrate selectivity of meta-cleavage product hydrolase by domain
      swapping.
AB  - meta-Cleavage product (MCP) hydrolases can catalyze relatively low reactive
      carbon-carbon bond hydrolysis of products, which are derived from the meta
      cleavage of catechols. The strict substrate selectivity of MCP hydrolases
      attracts an interest to understand the determinants of substrate specificity.
      Compared with conventional site-directed mutagenesis, domain swapping is an
      effective strategy to explore substrate specificity due to the large-scale
      reorganization of three-dimensional structure. In the present study, the hybrid
      MCP hydrolases BphDLidA and MfphALidD were constructed by exchanging the lid
      domain of two parental enzymes MfphA and BphD. The residues Gly130/Ala196 (MfphA)
      and Gly136/Ala211 (BphD) were selected as crossover points according to
      structural disruption score analysis and molecular dynamics simulations. It was
      shown that the hybrid enzymes exhibited similar substrate selectivity with the
      parent enzyme providing the lid domain. Docking studies suggested that the lid
      domain may play a key role in determining substrate specificity by reshaping the
      active pocket and modulating the orientation of the substrate.

PMID- 22996281
TI  - Quantification of viable but nonculturable bacterial pathogens in anaerobic
      digested sludge.
AB  - Enteric bacterial pathogens in sewage sludge easily become viable but
      nonculturable (VBNC) during anaerobic digestion, which escape detection by
      standard culture methods and pose a potential health risk. In this study, a
      method that is combining the standard culture method with the reverse
      transcription quantitative PCR (RT-qPCR) assay was developed for the
      quantification of bacterial pathogens in the VBNC state. The cycle threshold (CT)
      values from RT-qPCR assays were linear to the bacterial number in the range from
      109 to 102 most probable number (MPN) per reaction for Escherichia coli
      (R2=0.9964) and Salmonella typhimurium (R2=0.9938) and from 109 to 104 MPN per
      reaction for Shigella flexneri (R2=0.997), respectively. Mesophilic anaerobic
      digestion (MAD) caused the bacterial pathogens in sewage sludge entering into
      VBNC state with the incidence indexes of 0.01-1.12 for E. coli, 2.48-436.52 for
      S. typhimurium, and 4.17-6.61 for S. flexneri, respectively. Given different VBNC
      incidence indexes of bacterial pathogens in sewage sludge by MAD, the
      quantification results of VBNC pathogens using RT-qPCR could provide an improved
      evaluation of pathogen inactivation efficiency and biological safety in sludge
      anaerobic digestion.

PMID- 22996283
TI  - The role of mass spectrometry in the analysis of vitamin D compounds.
AB  - This review highlights the superseding role of mass spectrometry in the
      structural characterization and quantitation of vitamin D compounds in comparison
      to other analytical methods (e.g., UV, bioassays) that lack the sensitivity and
      specificity of mass spectrometry. After a short introduction to the biochemistry
      of vitamin D compounds, an overview of the current techniques to characterize and
      quantitate vitamin D compounds is given with emphasis on the contribution of mass
      spectrometry.

PMID- 22996284
TI  - Trityl radicals: spin labels for nanometer-distance measurements.
AB  - Spin labelling with trityls: to gather information about the structure and
      dynamics of trityl radicals, spin-labelled polymers were measured with pulsed
      electron-electron double resonance (PELDOR) and double-quantum coherence (DQC).
      This study demonstrates that trityl radicals have great potential as spin labels
      that eliminate some limitations of nitroxide spin labels.

PMID- 22996285
TI  - TFF3 and survivin expressions associate with a lower survival rate in gastric
      cancer.
AB  - Trefoil factor 3 (TFF3) and survivin with functions of inhibiting apoptosis are
      involved in the gastric cancer by overexpression. The purpose of this study is to
      examine the expression of TFF3 and survivin in patients' tissue samples with
      gastric cancer and analyze the relationship between the protein expression and
      the different clinical records. By studying the expressions of TFF3 and survivin
      in gastric cancer through immunohistochemical staining and examining the survival
      rate via Kaplan-Meier analysis for gastric cancer patients, we found that the
      TFF3 and survivin positive expressions have a significant relationship with the
      lower survival rate comparing to that of negative expressions in the analyzed
      patients (P < 0.05). And moreover, patients with double positive TFF3 and
      survivin expressions have the lowest survival rate. TFF3 or survivin positive
      expression correlates with the lymph node metastasis, metastasis, and TNM stages
      of gastric cancer. Survival analysis indicates that survival rate has a close
      relationship with the age, tumor histology, tumor differentiation, degree of
      infiltration, lymph node metastasis, distant metastasis, and TNM stages (P <
      0.01). Our data suggest that TFF3 and survivin expressions play a vital role in
      gastric cancer development, and these two proteins are important markers for
      prognosis in gastric cancer. Patients with gastric cancer can increase the
      survival rate through an earlier diagnosis and appropriate treatment. 

PMID- 22996286
TI  - Changes in human muscle oxygen saturation and mean fiber conduction velocity
      during intense dynamic exercise--effect of muscular training status.
AB  - INTRODUCTION: In this study we investigated whether an association exists between
      muscle fiber conduction velocity (MFCV) and local muscle oxygen saturation
      (StO(2)) in the superficial part of the latissimus dorsi muscle of runners and
      swimmers during exhaustive dynamic exercise. METHODS: Participants performed arm
      cranking with increasing intensity until exhaustion. RESULTS: Runners' MFCV was
      unchanged with increasing arm-cranking exercise intensity, but was higher (P <
      0.05) than swimmers' MFCV at the same workload. Swimmers' MFCV increased (P <
      0.05) with increasing exercise intensity and reached values at exhaustion similar
      to those of the runners. StO(2) was similar in swimmers and runners at rest and
      decreased with increasing exercise intensity. StO(2) was higher (P < 0.05) at the
      same workload in swimmers compared with runners. StO(2) and MFCV were
      significantly but very weakly correlated in both swimmers and runners.
      CONCLUSION: No association exists between surface MFCV and StO(2) in either
      trained or untrained human skeletal muscle during exhaustive intense dynamic
      exercise.

PMID- 22996287
TI  - Endogenous hippocampal LTD that is enabled by spatial object recognition requires
      activation of NMDA receptors and the metabotropic glutamate receptor, mGlu5.
AB  - Learning-facilitated synaptic plasticity describes the ability of hippocampal
      synapses to respond with persistent plasticity to afferent stimulation when
      coupled with a spatial learning event, whereby the afferent stimulation normally
      produces short-term plasticity or no change in synaptic strength if given in the
      absence of novel learning. Recently, it was reported that in the mouse
      hippocampus intrinsic long-term depression (LTD > 24 h) occurs when test-pulse
      afferent stimulation is coupled with a novel spatial learning. It is not known to
      what extent this phenomenon shares molecular properties with synaptic plasticity
      that is typically induced by means of patterned electrical afferent stimulation.
      In previous work, we showed that a novel spatial object recognition task
      facilitates LTD at the Schaffer collateral-CA1 synapse of freely behaving adult
      mice, whereas reexposure to the familiar spatial configuration ~24 h later
      elicited no such facilitation. Here we report that treatment with the NMDA
      receptor antagonist, (+/-)-3-(2-Carboxypiperazin-4-yl)-propanephosphonic acid
      (CPP), or antagonism of metabotropic glutamate (mGlu) receptor, mGlu5, using 2
      methyl-6-(phenylethynyl) pyridine (MPEP), completely prevented LTD under the
      novel learning conditions. Behavioral assessment during re-exposure after
      application of the antagonists revealed that the animals did not remember the
      object during novel exposure and treated them as if they were novel. Under these
      circumstances, where the acquisition of novel spatial information was involved,
      LTD was facilitated. Our data support that the endogenous LTD that is enabled
      through novel spatial learning in adult mice is critically dependent on the
      activation of both the NMDA receptors and mGlu5.

PMID- 22996289
TI  - Interferometric scattering microscopy (iSCAT): new frontiers in ultrafast and
      ultrasensitive optical microscopy.
AB  - Optical microscopes have for centuries been our window to the microscopic world.
      The advent of single-molecule optics over the past few decades has ushered in a
      new era in optical imaging, partly because it has enabled the observation of
      motion and more recently structure on the nanoscopic scale through the
      development of super-resolution techniques. The large majority of these studies
      have relied on the efficient detection of fluorescence as the basis of single
      molecule sensitivity. Despite the many advantages of using single emitters as
      light sources, the intensity and duration of their emission impose fundamental
      limits on the imaging speed and precision for tracking studies. Here, we discuss
      the potential of a novel imaging technique based on interferometric scattering
      (iSCAT) that pushes both the sensitivity and time resolution far beyond what is
      currently achievable by single-emitter-based approaches. We present recent
      results that demonstrate single-molecule sensitivity and imaging speeds on the
      microsecond timescale.

PMID- 22996290
TI  - New basis sets for the evaluation of interaction-induced electric properties in
      hydrogen-bonded complexes.
AB  - Interaction-induced static electric properties, that is, dipole moment,
      polarizability, and first hyperpolarizability, of the CO-(HF)(n) and N(2)
      (HF)(n), n = 1-9 hydrogen-bonded complexes are evaluated within the finite field
      approach using the Hartree-Fock, density functional theory, Moller-Plesset second
      order perturbation theory, and coupled cluster methods, and the LPol-n (n = ds,
      dl, fs, fl) basis sets. To compare the performance of the different methods with
      respect to the increase of the complex size, we consider as model systems linear
      chains of the complexes. We analyze the results in terms of the many-body and
      cooperative effects.

PMID- 22996291
TI  - Activated monocytes augment TRAIL-mediated cytotoxicity by human NK cells through
      release of IFN-gamma.
AB  - Natural killer (NK) cells are innate lymphocytes that are able to directly kill
      tumor cells through different mechanisms including ligation of TNF-related
      apoptosis-inducing ligand (TRAIL) receptors. Zoledronic acid (ZA) is a
      bisphosphonate known to upregulate the expression of TRAIL on human gammadelta T
      cells. Here, we investigated whether exposure to ZA would upregulate TRAIL
      expression on human NK cells and augment their cytotoxicity against tumor cells.
      When cocultured with monocytes, treatment with ZA and IL-2 resulted in a
      significant upregulation of TRAIL expression on human NK cells (p = 0.002).
      Consequently, ZA-primed NK cells were significantly more cytotoxic against TRAIL
      sensitive tumor cells (p < 0.0001). In the presence of ZA and IL-2, monocytes
      produced high levels of IFN-gamma; when cultured in the presence of neutralizing
      antibodies to IFN-gamma, TRAIL expression and TRAIL-mediated cytotoxicity of NK
      cells were significantly reduced. Furthermore, in tumor-bearing SCID/Beige mice,
      a significant delayed tumor progression and prolonged survival was observed after
      infusion of ZA-primed NK cells compared with that observed in mice infused with
      unprimed NK cells. These findings represent a novel approach to potentiate TRAIL
      mediated apoptosis by adoptively infused NK cells that could improve the outcome
      in patients with cancer.

PMID- 22996293
TI  - Using gas-phase guest-host chemistry to probe the structures of b ions of
      peptides.
AB  - Middle-sized b(n) (n >= 5) fragments of protonated peptides undergo selective
      complex formation with ammonia under experimental conditions typically used to
      probe hydrogen-deuterium exchange in Fourier transform ion cyclotron resonance
      mass spectrometry (FT-ICR-MS). Other usual peptide fragments like y, a, a*, etc.,
      and small b(n) (n <= 4) fragments do not form stable ammonia adducts. We propose
      that complex formation of b(n) ions with ammonia is characteristic to macrocyclic
      isomers of these fragments. Experiments on a protonated cyclic peptide and N
      terminal acetylated peptides fully support this hypothesis; the protonated cyclic
      peptide does form ammonia adducts while linear b(n) ions of acetylated peptides
      do not undergo complexation. Density functional theory (DFT) calculations on the
      proton-bound dimers of all-Ala b(4), b(5), and b(7) ions and ammonia indicate
      that the ionizing proton initially located on the peptide fragment transfers to
      ammonia upon adduct formation. The ammonium ion is then solvated by N(+)-H...O H
      bonds; this stabilization is much stronger for macrocyclic b(n) isomers due to
      the stable cage-like structure formed and entropy effects. The present study
      demonstrates that gas-phase guest-host chemistry can be used to selectively probe
      structural features (i.e., macrocyclic or linear) of fragments of protonated
      peptides. Stable ammonia adducts of b(9), b(9)-A, and b(9)-2A of A(8)YA, and
      b(13) of A(20)YVFL are observed indicating that even these large b-type ions form
      macrocyclic structures.

PMID- 22996294
TI  - Coupling of two multistep catalytic cycles for the one-pot synthesis of
      propargylamines from alcohols and primary amines on a nanoparticulated gold
      catalyst.
AB  - A one-pot reaction was performed with a nanoparticulated gold catalyst. A
      secondary amine is formed through N-monoalkylation of a primary amine with an
      alcohol by a borrowing hydrogen methodology in a three-step reaction. The
      secondary amine formed enters into a second A(3)-coupling cycle to give
      propargylamines. The multistep reaction requires a gold species formed and
      stabilized on a ceria surface.

PMID- 22996292
TI  - IFITM1 is a tight junction protein that inhibits hepatitis C virus entry.
AB  - Type 1 interferon (IFN) continues to be the foundation for the current standard
      of care combination therapy for chronic hepatitis C virus (HCV) infection, yet
      the component interferon-stimulated genes (ISGs) that mediate the antiviral
      actions of IFN are not fully defined. Interferon-induced transmembrane protein 1
      (IFITM1) is an ISG product that suppresses early stage infection by a number of
      viruses through an unknown mechanism of action. Moreover, the actions of IFITM1
      on HCV infection are not fully elucidated. Here we identify IFITM1 as a
      hepatocyte tight junction protein and a potent anti-HCV effector molecule. IFITM1
      expression is induced early during IFN treatment of hepatocytes and accumulates
      at hepatic tight junctions in HCV-infected human patient liver during IFN
      therapy. Additionally, we found that IFITM1 interacts with HCV coreceptors,
      including CD81 and occludin, to disrupt the process of viral entry. Thus, IFITM1
      is an anti-HCV ISG whose actions impart control of HCV infection through
      interruption of viral coreceptor function. CONCLUSION: This study defines IFITM1
      as an ISG effector with action against HCV entry. Design of therapy regimens to
      enhance IFITM1 expression should improve the virologic response among HCV
      patients undergoing treatment with type I IFN.

PMID- 22996295
TI  - Whole-genome-amplified DNA as a source for mutational analysis underestimates the
      frequency of mutations in pediatric acute myeloid leukemia.

PMID- 22996288
TI  - Current treatment options in (peri)myocarditis and inflammatory cardiomyopathy.
AB  - In inflammatory dilated cardiomyopathy and myocarditis there is--apart from heart
      failure and antiarrhythmic therapies--no alternative to an aetiologically driven
      specific treatment. Prerequisite are noninvasive and invasive biomarkers
      including endomyocardial biopsy and PCR on cardiotropic agents. This review deals
      with the different etiologies of myocarditis and inflammatory cardiomyopathy
      including the genetic background, the predisposition for heart failure and
      inflammation. It analyses the epidemiologic shift in pathogenetic agents in the
      last 20 years, the role of innate and aquired immunity including the T- and B
      cell driven immune responses. The phases and clinical faces of myocarditis are
      summarized. Up-to-date information on current treatment options starting with
      heart failure and antiarrhythmic therapy are provided. Although inflammation can
      resolve spontaneously, specific treatment directed to the causative aetiology is
      often required. For fulminant, acute and chronic autoreactive myocarditis
      immunosuppressive treatment is beneficial, while for viral cardiomyopathy and
      myocarditis ivIg can resolve inflammation and is as successful as interferon
      therapy in enteroviral and adenoviral myocarditis. For Parvo B19 and HHV6
      myocarditis eradication of the virus is still a problem by any of these treatment
      options. Finally, the potential of stem cell therapy has to be tested in future
      trials. In virus-negative, autoreactive perimyocardial disease a locoregional
      approach with intrapericardial instillation of high local doses of triamcinolone
      acetate has been shown to be highly efficient and with few systemic side-effects.

PMID- 22996297
TI  - Can we really prevent suicide?
AB  - Every year, suicide is among the top 20 leading causes of death globally for all
      ages. Unfortunately, suicide is difficult to prevent, in large part because the
      prevalence of risk factors is high among the general population. In this review,
      clinical and psychological risk factors are examined and methods for suicide
      prevention are discussed. Prevention strategies found to be effective in suicide
      prevention include means restriction, responsible media coverage, and general
      public education, as well identification methods such as screening, gatekeeper
      training, and primary care physician education. Although the treatment for
      preventing suicide is difficult, follow-up that includes pharmacotherapy,
      psychotherapy, or both may be useful. However, prevention methods cannot be
      restricted to the individual. Community, social, and policy interventions will
      also be essential.

PMID- 22996298
TI  - Is there anything really novel on the antidepressant horizon?
AB  - Major depression represents one of the most disabling illnesses worldwide and
      current treatments are only partially effective. All antidepressant agents
      modulate the monoamine system, which likely accounts for the similar efficacy
      profile of available treatments. Herein we summarize the current state of
      depression therapeutics and assess the antidepressant development pipeline.
      Antidepressant response rates in controlled trials are estimated at ~54 % and
      real-world effectiveness data suggests a somewhat lower rate. Response rates are
      lower still in patients who have not responded to previous treatment attempts and
      meaningful advancements will likely come only from identification of
      mechanistically novel agents. Monoaminergic agents largely dominate the
      antidepressant development pipeline, however the glutamate neurotransmitter
      system represents a bright spot on the antidepressant horizon. We review in
      detail findings regarding the antidepressant effects of the glutamate N-methyl-d
      aspartate receptor antagonist ketamine in order to highlight the promise of novel
      agents as future treatments for major depression.

PMID- 22996300
TI  - Female-to-male match predicted poor survival after living-donor liver
      transplantation-some issues needed to be clarified.

PMID- 22996299
TI  - Biological indicators of suicide risk in youth with mood disorders: what do we
      know so far?
AB  - Suicidal behaviour in youth is a major public health concern worldwide, and youth
      in the early stages of a primary mood disorder are an identifiable high-risk
      population. Neurobiological research in youth at risk for suicidality has sought
      to investigate the most promising parameters from research in adults. The present
      paper provides an overview of the current findings of neurobiological research in
      children and adolescents with mood disorders and suicidality including
      genetic/epigenetic findings, neuro-hormonal and immunological investigations.
      Longitudinal research in high-risk youth is a powerful way to investigate the
      influences and their pathways in determining suicidal risk in the context of a
      developing mood disorder. In the meantime, there are clear clinical indicators of
      risk to help identify youth who would benefit from close surveillance and early
      intervention.

PMID- 22996302
TI  - Multidrug-resistant Acinetobacter baumannii causing necrotizing fasciitis in a
      pancreas-kidney transplant recipient: a case report.

PMID- 22996303
TI  - Follow-up of tacrolimus breastfed babies.

PMID- 22996304
TI  - New technique in using the gonadal vein in lengthening the right renal vein in
      living donor kidney transplant.

PMID- 22996305
TI  - Effect of Wuzhi tablet (Schisandra sphenanthera extract) on the pharmacokinetics
      of cyclosporin A in rats.
AB  - In our previous reports, Wuzhi tablet (an herbal preparation of ethanol extract
      of Wuweizi (Schisandra sphenanthera)) can significantly increase the blood
      concentration of tacrolimus and paclitaxel in rats by inhibiting the CYP3A
      mediated metabolism and the P-gp-mediated efflux. Cyclosporin A (CsA), a well
      known immunosuppressant agent, is also a substrate of CYP3A and P-gp. Therefore,
      this study aimed to investigate whether and how WZ affects pharmacokinetics of
      CsA in rats. The AUC0-48 h and Cmax of CsA were increased by 40.1% and 13.1%,
      respectively, with a single oral co-administration of WZ and high dose of CsA
      (37.8 mg/kg). Interestingly, after a single oral co-administration of WZ and low
      dose of CsA (1.89 mg/kg), the AUC0-36 h and Cmax of CsA were dramatically
      increased by 293.1% (from 1103.2 +/- 293.0 to 4336.5 +/- 1728.3 ng.h/mL; p <
      0.05) and 84.1% (from 208.5 +/- 67.9 to 383.1 +/- 92.5 ng/mL; p < 0.05),
      respectively. The CL/F was decreased from 1.7 L/h/kg to 0.5 L/h/kg. Thus, the
      effect of WZ on high dose of CsA was not significant, but pharmacokinetic
      parameters of CsA at low dose were significantly influenced by co-administration
      of WZ. The herb-drug interaction should be taken into consideration at this
      situation.

PMID- 22996306
TI  - Shear wave elastography properties of vastus lateralis and vastus medialis
      obliquus muscles in normal subjects and female patients with patellofemoral pain
      syndrome.
AB  - OBJECTIVE: The aim of our study was to define and compare the mechanical
      properties of the vastus lateralis (VL) and vastus medialis obliquus muscles
      (VMO) by the way of quantitative shear-wave elastography in male and female
      healthy control (HC) subjects, and in female patients with patellofemoral pain
      syndrome (PFPS). MATERIALS AND METHODS: Twenty-two healthy volunteers (11 male
      and 11 female) and 11 female patients with anterior knee pain were included in
      the study. The SWE examinations for VL and VMO were performed while the subjects
      were performing open kinetic chain exercises in neutral and 30 degrees  hip
      abduction. The contraction capacity (CC) and contraction ratio (CR) values were
      determined in resting and contraction phases in both hip positions. RESULTS: The
      mean elasticity values in the CC for VL and VMO muscles were significantly higher
      in male HC subjects when compared to female HC subjects (p < 0.05). The CR of the
      VL muscle in female patients with PFPS was not significantly different than the
      female HC group. The CR for the VMO muscle was significantly lower in female
      patients with PFPS when compared to female HC subjects (p < 0.05). CONCLUSIONS:
      We found a significant VMO weakness, and this method may provide quantitative
      data that might influence the diagnosis of muscle weakness, in female patients
      with PFPS.

PMID- 22996307
TI  - Selective regulation of nicotine and polyamines biosynthesis in tobacco cells by
      enantiomers of ornithine.
AB  - L- and D-amino acids have diverse functions and effects on the metabolism,
      growth, and development of plants. Ornithine (Orn) plays a main role in the
      biosynthesis of many amino acids, nicotinic alkaloids, and polyamines in tobacco.
      This investigation describes the impact of Orn enantiomers on the production and
      distribution of free, conjugated, and bound polyamines, as well as nicotine in
      tobacco cells. It was recognized that the biosynthesis of metabolites was
      differently upregulated by each enantiomer. Putrescine was abundantly produced by
      exogenous L-ornithine (L-Orn), and both spermidine and spermine were
      significantly accumulated in D-ornithine (D-Orn)-supplied tobacco cells.
      Furthermore, nicotine production was highly upregulated by L-Orn, while the
      addition of D-Orn had no effect on the nicotine content of tobacco cells. It was
      observed that transcript expression of S-adenosylmethionine decarboxylase, as the
      key enzyme of spermidine/spermine biosynthesis, is coincident with their
      metabolic levels and is highly upregulated by D-Orn, as opposed to L-Orn. These
      results indicate that both enantiomers of Orn can trigger selected biosynthetic
      pathways in the cells, at the transcript level. Regarding these observations, it
      is proposed that L- and D-Orn function differently in the same biological
      pathways in which the latter, D-Orn specifically regulates important polyamines
      in the plant cells.

PMID- 22996308
TI  - Production of recombinant Agaricus bisporus tyrosinase in Saccharomyces
      cerevisiae cells.
AB  - It has been demonstrated that Agaricus bisporus tyrosinase is able to oxidize
      various phenolic compounds, thus being an enzyme of great importance for a number
      of biotechnological applications. The tyrosinase-coding PPO2 gene was isolated by
      reverse-transcription polymerase chain reaction (RT-PCR) using total RNA
      extracted from the mushroom fruit bodies as template. The gene was sequenced and
      cloned into pYES2 plasmid, and the resulting pY-PPO2 recombinant vector was then
      used to transform Saccharomyces cerevisiae cells. Native polyacrylamide gel
      electrophoresis followed by enzymatic activity staining with L-3,4
      dihydroxyphenylalanine (L-DOPA) indicated that the recombinant tyrosinase is
      biologically active. The recombinant enzyme was overexpressed and biochemically
      characterized, showing that the catalytic constants of the recombinant tyrosinase
      were higher than those obtained when a commercial tyrosinase was used, for all
      the tested substrates. The present study describes the  recombinant production of
      A. bisporus tyrosinase in active form. The produced enzyme has similar properties
      to the one produced in the native A. bisporus host, and its expression in S.
      cerevisiae provides good potential for protein engineering and functional studies
      of this important enzyme.

PMID- 22996309
TI  - Extracting actionable information from genome scans.
AB  - Genome-wide association studies discovered numerous genetic variants
      significantly associated with various phenotypes. However, significant signals
      explain only a small portion of the variation in many traits. One explanation is
      that missing variation is found in "suggestive signals," i.e., variants with
      reasonably small P-values. However, it is not clear how to capture this
      information and use it optimally to design and analyze future studies. We propose
      to extract the available information from a genome scan by accurately estimating
      the means of univariate statistics. The means are estimated by: (i) computing the
      sum of squares (SS) of a genome scan's univariate statistics, (ii) using SS to
      estimate the expected SS for the means (SSM) of univariate statistics, and (iii)
      constructing accurate soft threshold (ST) estimators for means of univariate
      statistics by requiring that the SS of these estimators equals the SSM. When
      compared to competitors, ST estimators explain a substantially higher fraction of
      the variability in true means. The accuracy of proposed estimators can be used to
      design two-tier follow-up studies in which regions close to variants having ST
      estimated means above a certain threshold are sequenced at high coverage and the
      rest of the genome is sequenced at low coverage. This follow-up approach reduces
      the sequencing burden by at least an order of magnitude when compared to a high
      coverage sequencing of the whole genome. Finally, we suggest ways in which ST
      methodology can be used to improve signal detection in future sequencing studies
      and to perform general statistical model selection.

PMID- 22996310
TI  - Hippocampal involvement in retrieval of odor vs. object memories.
AB  - The aim of this study was to investigate the role of the human hippocampus in
      episodic retrieval of odors, in comparison with episodic retrieval of visual
      objects. Subjects encoded a set of unique odors and objects, and retrieval was
      tested the next day during functional magnetic resonance imaging (fMRI). Subjects
      were shown the names of old (studied) and new (unstudied) odors and objects, and
      asked to indicate which of these stimuli had been presented the previous day. The
      results showed that brain activation was weaker and more restricted during
      retrieval of odors than during retrieval of objects, which possibly reflects a
      general visual dominance effect. Yet, retrieval of odors and objects yielded
      overlapping clusters of activation the bilateral hippocampi, and the left-sided
      activation was specifically increased during successful retrieval (hits > correct
      rejections) in both modalities. Moreover, retrieval of odors uniquely activated
      olfactory cortical regions, likely to reflect cortical reinstatement of sensory
      details. Our fMRI study is the first to make a direct comparison between
      olfactory and visual episodic memory, and the results provide clear evidence for
      modality-independent functions of the hippocampus.

PMID- 22996311
TI  - Hysteresis in the electromyography-force relationship: toward an optimal model
      for the estimation of force.
AB  - INTRODUCTION: In this study we analyzed the presence of hysteresis in the
      relationship between features of electromyography (EMG) and force. METHODS:
      Intramuscular EMG and surface EMG (sEMG) were recorded concurrently from the
      flexor digitorum profundus muscle from 0% to 100% maximum voluntary contraction
      (MVC) in 11 subjects. Two features, mean absolute value (MAV) and Wilson
      amplitude (WAMP), were computed using either the first-order (poly1) or third
      order (poly3) polynomial. RESULTS: We detected hysteresis in the EMG-force
      relationship for both features in all subjects. In general, the hysteresis-based
      models performed better than the overall model (which does not take into account
      the hysteresis in the EMG-force relationship), with R(2)  values about 0.98
      (averaged across subjects) and root mean square error around 5% of the MVC force.
      CONCLUSION: These results imply the existence of a path-dependent model, which
      may improve the accuracy of force estimation. Muscle Nerve, 2012.

PMID- 22996312
TI  - Full field image reconstruction is suitable for high-pitch dual-source computed
      tomography.
AB  - OBJECTIVES: The field of view (FOV) in high-pitch dual-source computed tomography
      (DSCT) is limited by the size of the second detector. The goal of this study was
      to develop and evaluate a full FOV image reconstruction technique for high-pitch
      DSCT. MATERIALS AND METHODS: For reconstruction beyond the FOV of the second
      detector, raw data of the second system were extended to the full dimensions of
      the first system, using the partly existing data of the first system in
      combination with a very smooth transition weight function. During the weighted
      filtered backprojection, the data of the second system were applied with an
      additional weighting factor. This method was tested for different pitch values
      from 1.5 to 3.5 on a simulated phantom and on 25 high-pitch DSCT data sets
      acquired at pitch values of 1.6, 2.0, 2.5, 2.8, and 3.0. Images were
      reconstructed with FOV sizes of 260 * 260 and 500 * 500 mm. Image quality was
      assessed by 2 radiologists using a 5-point Likert scale and analyzed with
      repeated-measure analysis of variance. RESULTS: In phantom and patient data, full
      FOV image quality depended on pitch. Where complete projection data from both
      tube-detector systems were available, image quality was unaffected by pitch
      changes. Full FOV image quality was not compromised at pitch values of 1.6 and
      remained fully diagnostic up to a pitch of 2.0. At higher pitch values, there was
      an increasing difference in image quality between limited and full FOV images (P
      = 0.0097). CONCLUSION: With this new image reconstruction technique, full FOV
      image reconstruction can be used up to a pitch of 2.0.

PMID- 22996313
TI  - Iodine quantification using dual-energy multidetector computed tomography
      imaging: phantom study assessing the impact of iterative reconstruction schemes
      and patient habitus on accuracy.
AB  - PURPOSE: The aim of this study was to assess the accuracy of iodine
      quantification based on spectral dual-energy computed tomography (DECT)
      extraction with additional noise reduction using iterative reconstruction in
      simulated optimal and obese patient environments. MATERIALS AND METHODS: Two
      custom-designed DECT phantoms were containing 10 vials with iodine concentrations
      representing arterial/parenchymal enhancement ranging from water isodensity to 
      150 Hounsfield units and, in addition, 40 vials simulating enhancement seen in
      nondiluted thoracic inlet vasculature and urinary bladder/renal collecting
      systems of up to -2000 Hounsfield units.Dual-energy computed tomography
      acquisition was performed using a dual-source scanner at 140 kVp/90 mAs and 80
      kVp/495 mAs. Backprojection-based soft tissue kernels and corresponding
      iteratively reconstructed kernels generated dual-energy series used for iodine
      extraction.Fractional variations between known and spectrally determined iodine
      concentration were calculated for each concentration step; paired t tests
      evaluated variations between backprojected and iteratively reconstructed data
      sets for small and obese phantoms. Bland-Altman plots with regression analyses
      assessed concentration differences observed in backprojected and iteratively
      reconstructed data. RESULTS: For backprojected data, mean concentration
      variations of 8.7% +/- 8.4 and 12.2% +/- 6.3 were detected in small and large
      phantoms, respectively, compared with significantly less variation observed in
      iteratively reconstructed data with 6.1% +/- 6.2 and 11.0% +/- 6.5, respectively.
      Dual-energy quantification systematically overestimated concentrations in lower
      concentration ranges and underestimated concentrations in higher concentration
      ranges. Regression analyses showed cubic distribution of concentration
      differences for backprojected (R = 0.697) and linear distribution for iteratively
      reconstructed data (R = 0.701). CONCLUSION: Spectral DECT-based iodine
      quantification is able to accurately quantify iodine in phantoms simulating
      optimal and large patients; iterative reconstruction improves the accuracy of
      iodine detection. Systematic deviations of the spectrally determined iodine
      concentrations could potentially be corrected with weighting curves.

PMID- 22996314
TI  - Apparent diffusion coefficient and sodium concentration measurements in human
      prostate tissue via hydrogen-1 and sodium-23 magnetic resonance imaging in a
      clinical setting at 3T.
AB  - INTRODUCTION: Multiparametric magnetic resonance imaging (MRI) of the prostate
      involves morphologic and functional imaging techniques, which could potentially
      enable to distinguish between common benign prostate diseases, especially
      prostatitis and prostate cancer. The aim of this study was to determine the
      apparent diffusion coefficient (ADC) and the tissue sodium concentration (TSC) in
      2 different regions of the human prostate, that is, the central gland (CG) and
      the peripheral gland (PG), by means of standard hydrogen-1 (H) MRI and
      quantitative sodium-23 (Na) MRI at 3 T to increase the spectrum of diagnostic
      parameters for prostate examinations. METHODS: All measurements were performed on
      a 3-T clinical whole-body magnetic resonance (MR) scanner. Na MR images were
      acquired with density-adapted 3-dimensional radial sequence and isotropic voxel
      resolution of 5 * 5 * 5 mm. After approval by the institutional review board and
      informed consent were obtained, 8 healthy volunteers were included in this study.
      Diffusion-weighted imaging and T2-weighted images were also recorded and hence
      enabled the correlation of measured TSC values with current state-of-the-art H
      MRI techniques. RESULTS: The ADC in both subregions was measured to be at normal
      levels (CG, 1.19 [0.09] *10 mm/s; PG, 1.54 [0.14] * 10 mm/s) in all 8 volunteers.
      Good spatial resolution of the Na images allowed for an easy identification of
      the same subregions from the Na MR images. In healthy adult volunteers (age, 29
      [2] years), the TSC was measured lower in central (55 [15] mmol/L) and higher in
      peripheral (69 [16] mmol/L) prostate tissue. A correlation between the TSC and
      the ADC in the 2 subregions was found in the same volunteer group (Pearson
      correlation coefficient = 0.87). DISCUSSION: For the first time, TSC was
      spatially resolved in human prostate tissue by means of Na MRI. Interestingly,
      the herein found TSC values of ~60 mmol/L were half as high as in a previously
      reported Na MRI study where prostate TSC was measured in 5-month-old mice. Future
      studies are required to determine the prostate TSC in cancer patients as well as
      in older volunteers. In conclusion, TSC can be measured in humans with
      sufficiently high spatial and temporal resolution at 3 T and could hence provide
      an additional noninvasive marker for the diagnosis of various prostate
      pathologies.

PMID- 22996315
TI  - Diffusion-weighted intravoxel incoherent motion imaging of renal tumors with
      histopathologic correlation.
AB  - PURPOSE: The aim of this study was to use intravoxel incoherent motion diffusion
      weighted imaging to discriminate subtypes of renal neoplasms and to assess
      agreement between intravoxel incoherent motion (perfusion fraction, fp) and
      dynamic contrast-enhanced magnetic resonance imaging (MRI) metrics of tumor
      vascularity. SUBJECTS AND METHODS: In this Health Insurance Portability and
      Accountability Act-compliant, institutional review board-approved prospective
      study, 26 patients were imaged at 1.5-T MRI using dynamic contrast-enhanced MRI
      with high temporal resolution and diffusion-weighted imaging using 8 b values
      (range, 0-800 s/mm). Perfusion fraction (fp), tissue diffusivity (Dt), and
      pseudodiffusivity (Dp) were calculated using biexponential fitting of the
      diffusion data. Apparent diffusion coefficient (ADC) was calculated with
      monoexponential fit using 3 b values of 0, 400, and 800 s/mm. Dynamic contrast
      enhanced data were processed with a semiquantitative method to generate model
      free parameter cumulative initial area under the curve of gadolinium
      concentration at 60 seconds (CIAUC60). Perfusion fraction, Dt, Dp, ADC, and
      CIAUC60 were compared between different subtypes of renal lesions. Perfusion
      fraction was correlated with CIAUC60. RESULTS: We examined 14 clear cell, 4
      papillary, 5 chromophobe, and 3 cystic renal cell carcinomas (RCCs). Although fp
      had higher accuracy (area under the curve, 0.74) for a diagnosis of clear cell
      RCC compared with Dt or ADC, the combination of fp and Dt had the highest
      accuracy (area under the curve, 0.78). The combination of fp and Dt diagnosed
      papillary RCC and cystic RCC with 100% accuracy, and clear cell RCC and
      chromophobe RCC, with 86.5% accuracy. There was significant strong correlation
      between fp and CIAUC60 (r = 0.82; P < 0.001). CONCLUSION: Intravoxel incoherent
      motion parameters fp and Dt can discriminate renal tumor subtypes. Perfusion
      fraction demonstrates good correlation with CIAUC60 and can assess degree of
      tumor vascularity without the use of exogenous contrast agent.

PMID- 22996316
TI  - Monochromatic x-rays for low-dose digital mammography: preliminary results.
AB  - PURPOSE: The feasibility of using monochromatic x-ray imaging generated from an x
      ray tube and a multilayer reflector for digital mammography with a low radiation
      dose was examined. MATERIALS AND METHODS: A multilayer mirror was designed to
      select the x-ray peak with an energy of 21.5 keV generated from an x-ray tube
      with a tungsten target and was fabricated by the ion-beam sputtering deposition
      system. Monochromatic x-ray images were obtained from an experimental digital
      mammography setup with a scanning stage. The performance of the system was
      evaluated using a breast phantom, a spectrometer, and a radiation dosimeter. We
      measured the contrast-to-noise ratio and performed the 10% modulation function
      test to determine image quality and resolution. RESULTS: The monochromatic beam
      from the multilayer reflector had a full-width-at-half-maximum of 0.9 keV at 21.5
      keV, and the reflectivity was 0.70, which was 90% of the designed value. The
      polychromatic and monochromatic x-rays showed radiation doses of 0.497 and 0.0415
      mGy, respectively. The monochromatic x-ray image shows fibers, calcifications,
      and masses more clearly than the polychromatic x-ray images do. The image
      contrast of the monochromatic x-rays was 1.85 times higher than that of the
      polychromatic x-rays. The experimental mammography setup had a spatial resolution
      of 7 lp/mm with both x-rays. CONCLUSION: Monochromatic x-rays generated using a
      multilayer mirror may be a useful diagnostic tool for breast examination by
      providing high contrast imaging with a low radiation dose.

PMID- 22996317
TI  - Ultrahigh-field 7-T magnetic resonance carotid vessel wall imaging: initial
      experience in comparison with 3-T field strength.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) of the vessel wall enables
      determination of luminal area, vessel wall thickness, and atherosclerotic plaque
      characteristics. For clinical application, high spatial resolution, derived from
      optimal signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), is
      paramount. Vessel wall MRI is expected to benefit from higher magnetic field
      strength. Therefore, the purposes of the present study were to develop an
      ultrahigh-field 7-T MRI hardware and protocols for vessel wall imaging of the
      carotid artery and to compare quantitative parameters of vessel wall morphology
      and image quality between 3-T and 7-T MRI. MATERIAL AND METHODS: Eighteen
      volunteers (11 men and 7 women; mean [SD] age, 29 [7] years) underwent MRI
      examinations at 7 T (using a custom-built surface transmit/receive coil of 15-cm
      diameter) and at 3 T (using a commercial phased-array coil with 2 flexible oval
      elements, 14 * 17 cm each). Magnetic resonance imaging of the left common carotid
      artery vessel wall was performed at 7 T with identical in-plane resolution as
      that of 3-T MRI (0.46 * 0.46 mm), providing transverse T1- and T2-weighted
      images. Blinded analysis of morphologic measurements (luminal area and vessel
      wall area), SNR for vessel wall (SNRVW), and the CNR between the lumen and the
      vessel wall were compared between 7 and 3 T. RESULTS: Morphologic carotid vessel
      wall measurements were comparable between 7 and 3 T for both T1-weighted images
      (luminal area: intraclass correlation [ICC], 0.81 and vessel wall area: ICC,
      0.84) and T2-weighted images (luminal area: ICC, 0.97 and vessel wall area: ICC,
      0.92). At 7 T, SNRVW and CNR were significantly higher compared with 3-T MRI for
      both T1- (P < 0.001) and T2-weighted images (P < 0.05), with gain factors ranging
      from 1.3 to 3.6. CONCLUSIONS: Ultrahigh-field 7-T MR carotid vessel wall imaging
      is feasible. 7-T MRI of the common carotid artery has comparable accuracy for
      determining luminal area and vessel wall area and has improved SNRVW and CNR
      compared with 3-T MRI. Therefore, ultrahigh-field 7-T vessel wall MRI may enable
      a more detailed assessment of plaque morphology.

PMID- 22996318
TI  - High throughput density functional investigations of the stability, electronic
      structure and thermoelectric properties of binary silicides.
AB  - The structural stabilities of binary Mg-X (X = Si, Ge, Sn) and 4d transition
      metal silicides Mo-Si and Ru-Si are investigated. The convex hulls of stable
      alloys are in overall good agreement with the known experimental phase diagrams.
      It is shown how the Si-rich Ru-Si structures have band gaps at the Fermi-level
      and how the Ru(2)Si(3) structure is stabilized compared to the corresponding
      Fe(2)Si(3) structure. We discuss the band structure of Ru(2)Si(3) and show how
      the anisotropic band masses lead to favorable calculated thermoelectric
      properties.

PMID- 22996319
TI  - Alloantigen-specific regulatory T cells prevent experimental chronic graft-versus
      host disease by simultaneous control of allo- and autoreactivity.
AB  - Chronic graft-versus-host disease (cGVHD) is characterised by a complex etiology
      of both alloimmune- and autoimmune-mediated disease progression and pathology,
      and is consequently difficult to control. The therapeutic potential of regulatory
      T (Treg) cells for cGVHD is currently being investigated; however, the relative
      ability of Treg cells with defined antigen specificities for auto- and
      alloantigen to prevent disease has not been previously examined. In this study,
      we show that donor-derived Treg-cell lines generated with self-MHC H-2(b) 
      specificity or specificity for BALB/c H-2(d)  alloantigen presented via the
      direct or indirect pathways are able to mediate an equal protection against cGVHD
      immune pathology in a disease model associated with recipient B-cell-driven
      humoral autoimmunity and glomerulonephritis. Mechanistically, autospecific Treg
      cells prevented disease induction by blocking donor T-cell engraftment whereas
      allospecific Treg cells permitted long-term engraftment of donor T cells. Donor T
      cells, while unresponsive to auto- and recipient alloantigens, retained the
      capacity to respond to third party alloantigens on ex vivo stimulation. These
      findings indicate that allospecific Treg cells may therefore be more clinically
      relevant as a cell therapy for cGVHD in the context of haplo-identical
      hematopoietic transplantation, as they allow persistence of donor T cells capable
      of responding to foreign antigens whilst preventing cGVHD-mediated autoimmunity.

PMID- 22996320
TI  - [Minimally invasive augmentation of the medial collateral ligament with
      autologous hamstring tendons in chronic knee instability].
AB  - OBJECTIVE: Medial collateral ligament reconstruction in chronic unstable knees.
      INDICATIONS: Chronic instability of the medial collateral ligament (MCL) isolated
      or in combination with multiligament injuries. CONTRAINDICATIONS: Refixable bony
      avulsions, limited range of motion, arthrofibrosis, severe valgus deformity,
      infections, critical soft tissue, lack of patient compliance and open growth
      plates. SURGICAL TECHNIQUE: Harvesting of the contralateral semitendinosus tendon
      and preparation. Supine position with leg in electric leg holder. Oblique skin
      incision above the pes anserinus parallel to the tendons. Placement of drill hole
      distal to the tibial insertion of the hamstrings in the footprint of the MCL.
      Tapering and fixation of the transplant. Subfascial tunneling and femoral
      fixation of the transplant distally to the medial patellofemoral ligament (MPFL)
      origin in 30 degrees  flexion under fluoroscopic control. Tibial fixation of the
      dorsal portion of the transplant (POL) ventral to the semimembranosus tendon
      footprint in full extension. POSTOPERATIVE MANAGEMENT: Limited weight bearing
      with 20 kg for 4-6 weeks, stabilizing brace with limited range of motion 0/0/90
      degrees . RESULTS: A total of 9 patients with a median age of 39 (18-70) years
      received an augmentation of the MCL complex due to a chronic instability using
      the described technique. Follow-up examination was performed after 16 (11-56)
      months. All patients reported a stable knee. The median value of the Lysholm
      score at follow-up was 90 (72-96) points and the Tegner score prior to trauma was
      4 (2-6) points and 3 (2-6) points during follow-up. No grade 2 or 3 instability
      could be observed during follow-up. There were no complications using the above
      mentioned technique.

PMID- 22996321
TI  - Metabolic profiling reveals disorder of carbohydrate metabolism in mouse
      fibroblast cells induced by titanium dioxide nanoparticles.
AB  - As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, their
      potential biosafety and metabolic mechanism needs to be fully explained. In this
      study, the cytotoxicity of homogeneous and weakly aggregated (< 100 nm) TiO(2)
      nanoparticles was investigated by analyzing the changes in metabolite profiles
      both in mouse fibroblast (L929) cells and their corresponding culture media using
      gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based
      metabolomic strategy. With multivariate statistics analysis, satisfactory
      separations were observed in principal component analysis (PCA) and orthogonal
      partial least squares discriminant analysis (OPLS-DA) models. Based on the
      variable importance in the OPLS-DA models, a series of differential metabolites
      were identified by comparison between TiO(2) nanoparticle-treated L929 cells or
      their corresponding culture media and the control groups. It was found that the
      major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO(2)
      nanoparticle-treated L929 cells and their corresponding culture media. These
      results might account for the serious damage to energy metabolism in mitochondria
      and the increased cellular oxidation stress in TiO(2) nanoparticle-induced L929
      cells. These results also suggest that the metabolomic strategy had a great
      potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was
      very helpful in understanding its underlying molecular mechanisms.

PMID- 22996322
TI  - Fixation positions after skipping saccades: a single space makes a large
      difference.
AB  - During reading, saccadic eye movements are generated to shift words into the
      center of the visual field for lexical processing. Recently, Krugel and Engbert
      (Vision Research 50:1532-1539, 2010) demonstrated that within-word fixation
      positions are largely shifted to the left after skipped words. However,
      explanations of the origin of this effect cannot be drawn from normal reading
      data alone. Here we show that the large effect of skipped words on the
      distribution of within-word fixation positions is primarily based on rather
      subtle differences in the low-level visual information acquired before saccades.
      Using arrangements of "x" letter strings, we reproduced the effect of skipped
      character strings in a highly controlled single-saccade task. Our results
      demonstrate that the effect of skipped words in reading is the signature of a
      general visuomotor phenomenon. Moreover, our findings extend beyond the scope of
      the widely accepted range-error model, which posits that within-word fixation
      positions in reading depend solely on the distances of target words. We expect
      that our results will provide critical boundary conditions for the development of
      visuomotor models of saccade planning during reading.

PMID- 22996323
TI  - Image artifacts from MR-based attenuation correction in clinical, whole-body
      PET/MRI.
AB  - PURPOSE: Integrated whole-body PET/MRI tomographs have become available. PET/MR
      imaging has the potential to supplement, or even replace combined PET/CT imaging
      in selected clinical indications. However, this is true only if methodological
      pitfalls and image artifacts arising from novel MR-based attenuation correction
      (MR-AC) are fully understood. RESULTS: Here we present PET/MR image artifacts
      following routine MR-AC, as most frequently observed in clinical operations of an
      integrated whole-body PET/MRI system. CONCLUSION: A clinical adoption of
      integrated PET/MRI should entail the joint image display and interpretation of MR
      data, MR-based attenuation maps and uncorrected plus attenuation-corrected PET
      images in order to recognize potential pitfalls from MR-AC and to ensure
      clinically accurate image interpretation.

PMID- 22996324
TI  - Herbal medicine for rheumatic diseases: promises kept?
AB  - Traditional healers throughout the world have relied on herbal medicines in their
      practices for millennia to treat a wide array of conditions, including arthritis.
      Present-day patients continue to seek care from complementary and alternative
      providers and more effective and less toxic treatments. A broad foundation of
      laboratory studies suggests that many herbal products have pertinent medicinal
      effects for the management of diseases like osteoarthritis and rheumatoid
      arthritis. However, few high quality clinical trials have yet been carried out to
      substantiate the safety and efficacy of herbal medicines. Some of the best
      research to date in this area is summarized in this review.

PMID- 22996326
TI  - Hepatic angiomyolipoma: CT and MR imaging findings with clinical-pathologic
      comparison.
AB  - OBJECTIVE: The objective of this study is to evaluate the clinical, pathologic,
      and computed tomography (CT) and/or magnetic resonance imaging (MRI) findings of
      hepatic angiomyolipoma (HAML) and to improve the diagnostic efficacy of the
      tumor. MATERIALS AND METHODS: Clinical, pathologic, and imaging findings were
      retrospectively evaluated in 18 patients with HAML. Two patients underwent both
      CT and MRI, ten underwent CT alone, and six underwent MRI alone. Unenhanced and
      contrast-enhanced examinations were performed in all patients. Imaging
      characteristics, such as the lesion location, lesion diameter, presence of early
      draining veins, attenuation/signal intensity of the lesions on imaging, and
      enhancement pattern were reviewed. RESULTS: There were 3 male and 15 female
      patients. HAML was seen as a well-defined, solitary mass on imaging with medium
      size (mean diameter, 5.9 cm). Fat was detected in ten patients. Calcification was
      noted in two patients and cystic degeneration was seen in one patient. Hepatic
      cirrhosis and capsule were not detected in all patients. The mean attenuation
      values exceeded 120 hounsfield units (HU) in 11 patients (91.7%). Peripherally
      decreasing enhancement rim as well as early draining vein was seen in 15 patients
      (83.3%). The early draining veins were all hepatic veins. Tumor vessels were
      noted in all patients. CONCLUSION: The presence of early draining vein,
      peripheral decreasing enhancement rim, and the absence of tumor capsule in the
      hypervascular hepatic tumor on CT and/or MRI together with normal alpha fetal
      protein may be helpful for the diagnosis of HAML in non-cirrhotic liver.

PMID- 22996325
TI  - Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine
      model of primary biliary cirrhosis.
AB  - Collectively, the data in both humans and murine models of human primary biliary
      cirrhosis (PBC) suggest that activated T cells, particularly CD8 T cells, play a
      critical role in biliary cell destruction. Under physiological conditions, T-cell
      activation involves two critical signals that involve the major
      histocompatibility complex and a set of costimulatory molecules, which include a
      receptor on T cells termed cytotoxic T lymphocyte antigen 4 (CTLA-4). Germane to
      the studies reported herein, signaling by CTLA-4 has the potential to modulate
      costimulation and induce inhibitory signals. In this study, we have taken
      advantage of our well-defined murine model of PBC, in which mice are immunized
      with 2-octynoic acid coupled to bovine serum albumin (2OA-BSA), leading to the
      production of high-titer antimitochondrial autoantibodies (AMAs) and portal
      cellular infiltrates. To investigate the potential of CTLA-4-Ig (immunoglobulin)
      as an immunotherapeutic agent, we treated mice both before and after induction of
      autoimmune cholangitis. First, we demonstrate that CTLA-4-Ig treatment, begun 1
      day before 2OA-BSA immunization, completely inhibits the manifestations of
      cholangitis, including AMA production, intrahepatic T-cell infiltrates, and bile
      duct damage. However, and more critically, treatment with CTLA-4-Ig, initiated
      after the development of autoimmune cholangitis in previously immunized mice,
      also resulted in significant therapeutic benefit, including reduced intrahepatic
      T-cell infiltrates and biliary cell damage, although AMA levels were not altered.
      CONCLUSION: These data suggest that an optimized regimen with CTLA-4-Ig has the
      potential to serve as an investigative therapeutic tool in patients with PBC.

PMID- 22996327
TI  - Structural changes in a protein fragment from abalone shell during the
      precipitation of calcium carbonate.
AB  - Mineralized tissues grow through biologically controlled processes in which
      specific macromolecules are involved. Some of these molecules, which are present
      in very low concentrations and are difficult to localize and characterize, become
      entrapped inside the mineralized tissue. Herein, a protein fragment, GP, which
      was obtained by the alkaline digestion of the green sheet of the abalone shell,
      is used as a probe to study the changes in molecular structure that occur during
      the precipitation of calcium carbonate. This important goal was achieved by
      exploiting a fluorescent tag in GP. The experimental results that were obtained
      by using spectroscopic-, chromatographic-, and microscopic techniques indicate
      that GP controls the precipitation kinetics and morphology of calcium carbonate
      crystals, and that it only undergoes structural reorganization when entrapped
      inside calcium carbonate crystals. To the best of our knowledge, this report
      represents one of the first studies on the conformational changes of a protein
      fragment that is involved in biomineralization processes on moving from the
      solution phase into the mineral phase.

PMID- 22996329
TI  - Improving neural response to sound improves reading.

PMID- 22996330
TI  - Do not throw equations out with the theory bathwater.

PMID- 22996328
TI  - TGF-beta blockade improves the distribution and efficacy of therapeutics in
      breast carcinoma by normalizing the tumor stroma.
AB  - Although the role of TGF-beta in tumor progression has been studied extensively,
      its impact on drug delivery in tumors remains far from understood. In this study,
      we examined the effect of TGF-beta blockade on the delivery and efficacy of
      conventional therapeutics and nanotherapeutics in orthotopic mammary carcinoma
      mouse models. We used both genetic (overexpression of sTbetaRII, a soluble TGF
      beta type II receptor) and pharmacologic (1D11, a TGF-beta neutralizing antibody)
      approaches to block TGF-beta signaling. In two orthotopic mammary carcinoma
      models (human MDA-MB-231 and murine 4T1 cell lines), TGF-beta blockade
      significantly decreased tumor growth and metastasis. TGF-beta blockade also
      increased the recruitment and incorporation of perivascular cells into tumor
      blood vessels and increased the fraction of perfused vessels. Moreover, TGF-beta
      blockade normalized the tumor interstitial matrix by decreasing collagen I
      content. As a result of this vessel and interstitial matrix normalization, TGF
      beta blockade improved the intratumoral penetration of both a low-molecular
      weight conventional chemotherapeutic drug and a nanotherapeutic agent, leading to
      better control of tumor growth.

PMID- 22996331
TI  - No evidence that equations cause impeded communication among biologists.

PMID- 22996332
TI  - Mathematical illiteracy impedes progress in biology.

PMID- 22996333
TI  - A suggestion on improving mathematically heavy papers.

PMID- 22996334
TI  - Genome-wide analysis and expression profiling of half-size ABC protein subgroup G
      in rice in response to abiotic stress and phytohormone treatments.
AB  - The roles of the proteins encoded by half-size adenosine triphosphate-binding
      cassette transporter subgroup G (ABCG) genes in abiotic stress responses are
      starting to be established in the dicot model Arabidopsis thaliana. In the
      monocot model rice, the functions of most half-size ABCG proteins in abiotic
      stress responses are unknown. Rcn1/OsABCG5 is an essential transporter for growth
      and development under abiotic stress, but its molecular function remains largely
      unclear. Here, we present a comprehensive overview of all 30 half-size ABCG genes
      in rice, including their gene structures, phylogeny, chromosome locations, and
      conserved motifs. Phylogenetic analysis revealed that the half-size OsABCG
      proteins were divided to four classes. All seven rice intronless genes, including
      Rcn1/OsABCG5, were in Class III, like the 12 intronless ABCG genes of
      Arabidopsis. The EST and FL-cDNA databases provided expression information for 25
      OsABCG genes. Semi-quantitative and quantitative RT-PCR analyses demonstrated
      that seven OsABCG genes were up-regulated in seedlings, shoots or roots following
      treatments with abiotic stresses (6, 17, 42  degrees C, NaCl, or mannitol) and
      abscisic acid. Another 15 OsABCG genes were up-regulated under at least one of
      the abiotic stress conditions and other phytohormones besides abscisic acid.
      Hierarchical clustering analysis of gene expression profiles showed that
      expression of the OsABCG genes could be classified into four clusters. The
      Rcn1/OsABCG5 cluster was up-regulated by abscisic acid and included OsABCG2, 3,
      13, and 27. The present study will provide a useful reference for further
      functional analysis of the ABCGs in monocots.

PMID- 22996335
TI  - Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone
      consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly
      unfit myeloma patients.
AB  - This multicenter phase II trial evaluated the safety and efficacy of lenalidomide
      prednisone (RP) induction, followed by lenalidomide-melphalan-prednisone (MPR)
      consolidation and RP maintenance in elderly unfit newly diagnosed myeloma
      patients. Patients received four 28-day RP induction courses (lenalidomide 25
      mg/day on days 1-21 and prednisone 50 mg three times/week), followed by six 28
      day MPR consolidation cycles (melphalan 2 mg, prednisone 50 mg three times/week
      and lenalidomide 10-15 mg/day on days 1-21), and maintenance with lenalidomide
      (10 mg/day on days 1-21 every 28 days) plus prednisone (25 mg three times/week).
      Forty-six patients were enrolled. Median age was 75 years, 59% of patients had at
      least one comorbidity and 35% at least two. Partial response rate was 80%,
      including 29% very good partial response. Median time to progression was 19.6
      months, median progression-free survival was 18.4 months and 2-year overall
      survival was 80%. At the tolerated consolidation dose (melphalan 25 mg/month and
      lenalidomide 10 mg/day), the most frequent grade 3 adverse events were
      neutropenia (36.4%), anemia (12.1%), cutaneous reactions (18.2%) and infections
      (12.1%). Grade 4 neutropenia occurred in 12.1% of patients. In conclusion, RP
      induction followed by MPR consolidation and RP maintenance showed a manageable
      safety profile, and reduced the risk of severe hematological toxicity in unfit
      elderly myeloma patients.

PMID- 22996336
TI  - PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced
      drug resistance in myeloma.
AB  - Chemoresistance is the major obstacle in multiple myeloma (MM) management. We
      previously showed that macrophages protect myeloma cells, on a cell contact
      basis, from melphalan or dexamethasone-induced apoptosis in vitro. In this study,
      we found that macrophage-mediated myeloma drug resistance was also seen with
      purified macrophages from myeloma patients' bone marrow (BM) in vitro and was
      confirmed in vivo using the human myeloma-SCID (severe combined immunodeficient)
      mouse model. By profiling differentially regulated and paired plasma membrane
      protein genes, we showed that PSGL-1 (P-selectin glycoprotein ligand-1)/selectins
      and ICAM-1/CD18 played an important role in macrophage-mediated myeloma cell drug
      resistance, as blocking antibodies against these molecules or genetic knockdown
      of PSGL-1 or ICAM-1 in myeloma cells repressed macrophages' ability to protect
      myeloma cells. Interaction of macrophages and myeloma cells via these molecules
      activated Src and Erk1/2 kinases and c-myc pathways and suppressed caspase
      activation induced by chemotherapy drugs. Thus, our study sheds new light on the
      mechanism of drug resistance in MM and provides novel targets for improving the
      efficacy of chemotherapy in patients.

PMID- 22996337
TI  - On the nature of three-dimensional encoding in the cognitive map: Commentary on
      Hayman, Verriotis, Jovalekic, Fenton, and Jeffery.
AB  - A recent article by Hayman, Verriotis, Jovalekic, Fenton, and Jeffery titled
      Anisotropic encoding of three-dimensional space by place cells and grid cells
      (2011) explored how place and grid cells respond when rats locomote vertically
      above the ground. From their results the authors concluded a number of points
      about rats' abilities to orient and navigate in three dimensions. Here, we review
      evidence revolving around several issues including: (1) what reference frame rats
      use when locomoting vertically, (2) whether rats can perceive their height above
      the ground, (3) whether rats can estimate vertical distance and have a cognitive
      map in the vertical domain, (4) whether rats can path integrate in the vertical
      domain, and (5) does processing 3-dimensional representations require a large
      number of neurons. We argue that the Hayman et al. results can be accounted for
      by considering the reference frame the animals used in the tasks. Had the rats
      been facing inward with their limbs in contact with the vertical surface when
      moving, it is possible that different patterns of place and grid cell activity
      would have been observed. Further, there is good evidence to indicate that rats
      can orient and navigate effectively in the vertical domain.

PMID- 22996341
TI  - Return to work and cancer: the Australian experience.
AB  - PURPOSE: Research suggests that for many cancer survivors, returning to work has
      a range of benefits. However, considerable barriers have been identified as
      influencing the quality of return to work outcomes. This study explored the
      perspectives of Australian cancer survivors, managers and employee assistance
      program (EAP) professionals to gain an understanding of the return to work
      process and factors that affect the experience. METHODS: Focus groups and
      interviews were conducted with cancer survivors (n = 15), managers (n = 12), and
      EAP professionals / psychologists (n = 4) from public and private sectors.
      Thematic analysis was used to analyse the data to identify common and unique
      themes from the three participant groups. RESULTS: A range of drivers were
      identified including maintaining normality and regaining identity, which could
      act positively or negatively depending on survivors' coping ability and self
      awareness. Analysis revealed communication difficulties in the workplace that
      impact on emotional and practical support. Negotiating an employee's return is
      complex, influenced by the level of consultation with the employee and use of an
      ad hoc or structured process. Direct and indirect ways of supporting employees
      with cancer were identified, as was the need for colleague and manager support.
      CONCLUSION: This study supports previous research findings of the impact of
      cancer on work, and reveals managers' lack of knowledge on how to respond
      appropriately. The process of returning to work is complex, influenced by
      employees' and managers' attitudes, communication skills and coping abilities.
      Areas for workplace interventions to optimise support for the cancer survivor are
      described.

PMID- 22996342
TI  - Clinician-patient agreement about the work disability problem of patients having
      persistent pain: why it matters.
AB  - BACKGROUND: Studies from different fields documenting the differences between
      clinicians' and workers' representations have not elucidated where the
      differences exist or how they can be resolved. PURPOSE: To define and describe
      scenarios depicting the differences between clinical judgment, workers'
      representations about their disability and clinicians' interpretations of these
      representations. METHODS: A multiple case-study design was used. Semi-structured
      prospective interviews were conducted at four points in time, with five
      clinicians managing 12 cases of workers having persistent pain and participating
      in an evidence-based work rehabilitation program. RESULTS: Four scenarios
      depicting differences in representations were found, but not all the differences
      necessarily had a negative impact on the program outcomes. For the clinicians,
      clear identification of the problem was important to allow for the use of
      concrete, pragmatic strategies. For the workers, congruence between the proposed
      strategy and their representations was crucial. CONCLUSION: During
      rehabilitation, the objectives must be acceptable to both parties or the proposed
      strategy must, at least, make sense to the patient.

PMID- 22996344
TI  - Physicochemical and antioxidant properties of Algerian honey.
AB  - The aim of the present study was to characterize the physical, biochemical and
      antioxidant properties of Algerian honey samples (n = 4). Physical parameters,
      such as pH, moisture content, electrical conductivity (EC), total dissolved
      solids (TDS), color intensity, total sugar and sucrose content were measured.
      Several biochemical and antioxidant tests were performed to determine the
      antioxidant properties of the honey samples. The mean pH was 3.84 +/- 0.01, and
      moisture the content was 13.21 +/- 0.16%. The mean EC was 0.636 +/- 0.001, and
      the mean TDS was 316.92 +/- 0.92. The mean color was 120.58 +/- 0.64 mm Pfund,
      and the mean 5-hydroxymethylfurfural (HMF) content was 21.49 mg/kg. The mean
      total sugar and reducing sugar contents were 67.03 +/- 0.68 g/mL and 64.72 +/-
      0.52 g/g, respectively. The mean sucrose content was 2.29 +/- 0.65%. High mean
      values of phenolic (459.83 +/- 1.92 mg gallic acid/kg), flavonoid (54.23 +/- 0.62
      mg catechin/kg), ascorbic acid (159.70 +/- 0.78 mg/kg), AEAC (278.15 +/- 4.34
      mg/kg), protein (3381.83 +/- 6.19 mg/kg) and proline (2131.47 +/- 0.90) contents,
      as well as DPPH (39.57% +/- 4.18) and FRAP activities [337.77 +/- 1.01 uM Fe
      (II)/100 g], were also detected, indicating that Algerian honey has a high
      antioxidant potential. Strong positive correlations were found between flavonoid,
      proline and ascorbic acid contents and color intensity with DPPH and FRAP values.
      Thus, the present study revealed that Algerian honey is a good source of
      antioxidants.

PMID- 22996343
TI  - Serological muscle loss biomarkers: an overview of current concepts and future
      possibilities.
AB  - BACKGROUND: The skeletal muscle mass is the largest organ in the healthy body,
      comprising 30-40 % of the body weight of an adult man. It confers protection from
      trauma, locomotion, ventilation, and it represents a "sink" in glucose metabolism
      and a reservoir of amino acids to other tissues such as the brain and blood
      cells. Naturally, loss of muscle has dire consequences for health as well as
      functionality. Muscle loss is a natural consequence of especially aging,
      inactivity, and their associated metabolic dysfunction, but it is strongly
      accelerated in critical illness such as organ failure, sepsis, or cancer. Whether
      this muscle loss is considered a primary or secondary condition, it is known that
      muscle loss is a symptom that predicts morbidity and mortality and one that is
      known to impact quality of life and independence. Therefore, monitoring of muscle
      mass is relevant in a number of pathologies as well as in clinical trials as
      measures of efficacy as well as safety. METHODS AND RESULTS: Existing biomarkers
      of muscle mass or muscle loss have shown to be either too unreliable or too
      impractical in relation to the perceived clinical benefit to reach regular
      clinical research or use. We suggest serological neoepitope biomarkers as a
      possible technology to address some of these problems. Blood biomarkers of this
      kind have previously been shown to respond with high sensitivity and shorter time
      to minimum significant change than available biomarkers of muscle mass. We
      provide brief reviews of existing muscle mass or function biomarker technologies,
      muscle protein biology, and existing neoepitope biomarkers and proceed to present
      tentative recommendations on how to select and detect neoepitope biomarkers.
      CONCLUSION: We suggest that serological peptide biomarkers whose tissue and
      pathology specificity are derived from post-translational modification of
      proteins in tissues of interest, presenting so-called neoepitopes, represents an
      exciting candidate technology to fill out an empty niche in biomarker technology.

PMID- 22996345
TI  - Salvianolic acid A protects the peripheral nerve function in diabetic rats
      through regulation of the AMPK-PGC1alpha-Sirt3 axis.
AB  - Salvianolic acid A (SalA) is one of the main efficacious, water-soluble
      constituents of Salvia miltiorrhiza Bunge. This study investigated the protective
      effects of SalA on peripheral nerve in diabetic rats. Administration of SalA
      (0.3, 1 and 3 mg/kg, ig) was started from the 5th week after strepotozotocin
      (STZ60 mg/kg) intraperitoneal injection and continued for 8 weeks. Paw withdrawal
      mechanical threshold (PWMT) and motor nerve conduction velocity (MNCV) were used
      to assess peripheral nerve function. The western blot methods were employed to
      test the expression levels of serine-threonine liver kinase B1 (LKB1), AMP
      activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PGC-1alpha), silent information regulator protein3 (sirtuin
      3/Sirt3) and neuronal nitric oxide synthase (nNOS) in sciatic nerve. Results
      showed that SalA administration could increase PWMT and MNCV in diabetic rats;
      reduce the deterioration of sciatic nerve pathology; increase AMPK
      phosphorylation level, up-regulate PGC-1alpha, Sirt3 and nNOS expression, but had
      no influence on LKB1. These results suggest that SalA has protective effects
      against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve
      function in diabetic rats might be attributed to improvements in glucose
      metabolism through regulation of the AMPK-PGC1alpha-Sirt3 axis.

PMID- 22996346
TI  - Bioassay-guided isolation and identification of cytotoxic compounds from
      Gymnosperma glutinosum leaves.
AB  - Bioassay-guided fractionation of hexane extracts of Gymnosperma glutinosum
      (Asteraceae) leaves, collected in North Mexico, afforded the known compounds
      hentriacontane (1) and (+)-13S,14R,15-trihydroxy-ent-labd-7-ene (2), as well as
      the new ent-labdane diterpene (-)-13S,14R,15-trihydroxy-7-oxo-ent-labd-8(9)-ene
      (3). In addition, D-glycero-D-galactoheptitol (4) was isolated from the
      methanolic extract of this plant. Their structures were established on the basis
      of high-field 1D- and 2D NMR methods supported by HR-MS data. The cytotoxic
      activity was determined by using the in vitro L5178Y-R lymphoma murine model.
      Hentriacontane (1) and the new ent-labdane 3 showed weak cytotoxicity, whereas
      the ent-labdane 2 showed significant (p < 0.05) and concentration dependent
      cytotoxicity (up to 78%) against L5178Y-R cells at concentrations ranging from
      7.8 to 250 MUg/mL.

PMID- 22996347
TI  - A phytoanticipin derivative, sodium houttuyfonate, induces in vitro synergistic
      effects with levofloxacin against biofilm formation by Pseudomonas aeruginosa.
AB  - Antibiotic resistance has become the main deadly factor in infections, as
      bacteria can protect themselves by hiding in a self-constructed biofilm.
      Consequently, more attention is being paid to the search for "non-antibiotic
      drugs" to solve this problem. Phytoanticipins, the natural antibiotics from
      plants, could be a suitable alternative, but few works on this aspect have been
      reported. In this study, a preliminary study on the synergy between sodium
      houttuyfonate (SH) and levofloxacin (LFX) against the biofilm formation of
      Pseudomonas aeruginosa was performed. The minimal inhibitory concentrations (MIC)
      of LFX and SH, anti-biofilm formation and synergistic effect on Pseudomonas
      aeruginosa, and quantification of alginate were determined by the microdilution
      method, crystal violet (CV) assay, checkerboard method, and hydroxybiphenyl
      colorimetry. The biofilm morphology of Pseudomonas aeruginosa was observed by
      fluorescence microscope and scanning electric microscope (SEM). The results
      showed that: (i) LFX and SH had an obvious synergistic effect against Pseudomonas
      aeruginosa with MIC values of 0.25 MUg/mL and 128 MUg/mL, respectively; (ii) 1/2
      * MIC SH combined with 2 * MIC LFX could suppress the biofilm formation of
      Pseudomonas aeruginosa effectively, with up to 73% inhibition; (iii) the
      concentration of alginate decreased dramatically by a maximum of 92% after
      treatment with the combination of antibiotics; and (iv) more dead cells by
      fluorescence microscope and more removal of extracellular polymeric structure
      (EPS) by SEM were observed after the combined treatment of LFX and SH. Our
      experiments demonstrate the promising future of this potent antimicrobial agent
      against biofilm-associated infections.

PMID- 22996348
TI  - Utilizing graph theory to select the largest set of unrelated individuals for
      genetic analysis.
AB  - Many statistical analyses of genetic data rely on the assumption of independence
      among samples. Consequently, relatedness is either modeled in the analysis or
      samples are removed to "clean" the data of any pairwise relatedness above a
      tolerated threshold. Current methods do not maximize the number of unrelated
      individuals retained for further analysis, and this is a needless loss of
      resources. We report a novel application of graph theory that identifies the
      maximum set of unrelated samples in any dataset given a user-defined threshold of
      relatedness as well as all networks of related samples. We have implemented this
      method into an open source program called Pedigree Reconstruction and
      Identification of a Maximum Unrelated Set, PRIMUS. We show that PRIMUS
      outperforms the three existing methods, allowing researchers to retain up to 50%
      more unrelated samples. A unique strength of PRIMUS is its ability to weight the
      maximum clique selection using additional criteria (e.g. affected status and data
      missingness). PRIMUS is a permanent solution to identifying the maximum number of
      unrelated samples for a genetic analysis.

PMID- 22996349
TI  - Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of
      Withania somnifera roots in Wistar rats.
AB  - Withania somnifera is a widely used medicinal plant for several disorders.
      Toxicity studies on Withania somnifera are not available. Acute and sub-acute
      oral toxicities of Withania somnifera root extract in Wistar rats were evaluated
      in the present study. In the acute toxicity study, WSR extract was administered
      to five rats at 2000 mg/kg, once orally and were observed for 14 days. No toxic
      signs/mortality were observed. In the sub-acute study, WSR extract was
      administered once daily for 28 days to rats at 500, 1000 and 2000 mg/kg, orally.
      No toxic signs/mortality were observed. There were no significant changes (P <
      0.05) in the body weights, organ weights and haemato-biochemical parameters in
      any of the dose levels. No treatment related gross/histopathological lesions were
      observed. The present investigation demonstrated that the no observed adverse
      effect level was 2000 mg/kg body weight per day of hydroalcoholic extract of W.
      somnifera in rats and hence may be considered as non-toxic.

PMID- 22996350
TI  - The effect of temperature on amount and structure of motor variability during 2
      minute maximum voluntary contraction.
AB  - INTRODUCTION: In this study, we questioned whether local cooling of muscle or
      heating involving core and muscle temperatures are the main indicators for force
      variability. METHODS: Ten volunteers performed a 2-min maximum voluntary
      contraction (MVC) of the knee extensors under control (CON) conditions after
      passive heating (HT) and cooling (CL) of the lower body. RESULTS: HT increased
      muscle and rectal temperatures, whereas CL lowered muscle temperature but did not
      affect rectal temperature. During 2-min MVC, peak force decreased to a lower
      level in HT compared with CON and CL experiments. Greater central fatigue was
      found in the HT experiment, and there was less in the CL experiment than in the
      CON experiment. CONCLUSIONS: Increased core and muscle temperature increased
      physiological tremor and the amount and structural complexity of force
      variability of the exercising muscles, whereas local muscle cooling decreased all
      force variability variables measured.

PMID- 22996351
TI  - Tailored crystalline microporous materials by post-synthesis modification.
AB  - Crystalline microporous solids are an important class of inorganic materials with
      uses in different areas impacting our everyday lives, namely as catalysts,
      adsorbents, and ion exchangers. Advancements in synthesis have been invaluable in
      expanding the classical aluminosilicate zeolites to new unique framework types
      and compositions, motivating innovative developments. However, the inexhaustible
      post-synthetic options to tailor zeolite properties have been and will continue
      to be indispensable to realize emerging and to improve conventional applications.
      Starting from the routine drying and template removal processes that every
      zeolite must experience prior to use, a wide spectrum of treatments exists to
      alter individual or collective characteristics of these materials for optimal
      performance. This review documents the toolbox of post-synthetic strategies
      available to tune the properties of zeolitic materials for specific functions.
      The categorisation is based on the scale at which the alteration is aimed at,
      including the atomic structure (e.g. the introduction, dislodgment, or
      replacement of framework atoms), the micropore level (e.g. template removal and
      functionalisation by inorganic and organic species), and the crystal and particle
      levels (e.g. the introduction of auxiliary porosity). Through examples in the
      recent literature, it is shown that the combination of post-synthetic methods
      enables rational zeolite design, extending the characteristics of these materials
      way beyond those imposed by the synthesis conditions.

PMID- 22996352
TI  - Mn2Au: body-centered-tetragonal bimetallic antiferromagnets grown by molecular
      beam epitaxy.
AB  - Mn(2)Au, a layered bimetal, is successfully grown using molecular beam epitaxy
      (MBE). The experiments and theoretical calculations presented suggest that
      Mn(2)Au film is antiferromagnetic with a very low critical temperature. The
      antiferromagnetic nature is demonstrated by measuring the exchange-bias effect of
      Mn(2)Au/Fe bilayers. This study establishes a primary basis for further research
      of this new antiferromagnet in spin-electronic device applications.

PMID- 22996353
TI  - Patterns and predictors of multiple sexual partnerships among newly arrived
      Latino migrant men.
AB  - Multiple sexual partnerships (MSP), both concurrent and serial short gap, are
      thought to increase the risk of HIV and sexually transmitted infection (STI)
      acquisition and transmission. In this study we evaluate potential individual and
      environmental risk factors for engaging in MSP in a cohort of newly arrived
      Latino migrant men (LMM) in New Orleans, LA, USA. Participants were surveyed at
      three time points over a nine-month period to examine factors associated with
      MSP. Of the 113 men, 32.5 % reported ever MSP. In 290 observations, 19.5 % of men
      had concurrent, and 15.0 % had serial short gap partnerships in at least one
      interviews. Substance was associated with MSP, OR (95 % CI) 2.00 (1.16, 3.45)
      whereas belonging to a community organization was found to be protective, OR 0.32
      (0.17, 0.59). Interventions to reduce substance use and promote social connection
      are needed to prevent a potential HIV/STI epidemic in this population. 

PMID- 22996354
TI  - EBV stimulates TLR- and autophagy-dependent pathways and impairs maturation in
      plasmacytoid dendritic cells: implications for viral immune escape.
AB  - Plasmacytoid DCs (pDCs) are crucial mediators in the establishment of immunity
      against most viruses, given their extraordinary capacity to produce a massive
      quantity of type I IFN. In this study we investigate the response of pDCs to
      infection with EBV, a gamma-herpes virus that persists with an asymptomatic
      infection in immunocompetent hosts, although in certain conditions it can promote
      development of cancers or autoimmune diseases. We show that high amounts of type
      I IFNs were released from isolated pDCs after exposure to EBV by a mechanism
      requiring TLRs and a functional autophagic machinery. We next demonstrate that
      EBV can infect pDCs via viral binding to MHC class II molecule HLA-DR and that
      pDCs express EBV-induced latency genes. Furthermore, we observe that EBV is able
      to induce activation but not maturation of pDCs, which correlates with an
      impaired TNF-alpha release. Accordingly, EBV-infected pDCs are unable to mount a
      full T-cell response, suggesting that impaired pDC maturation, combined with a
      concomitant EBV-mediated upregulation of the T-cell inhibitory molecules B7-H1
      and ICOS-L, could represent an immune-evasion strategy promoted by the virus.
      These mechanisms might lead to persistence in immunocompetent hosts or to
      dysregulated immune responses linked to EBV-associated diseases.

PMID- 22996355
TI  - Reversed assembly of dyes in an RNA duplex compared with those in DNA.
AB  - We prepared reversed dye clusters by hybridizing two RNA oligomers, each of which
      tethered dyes (Methyl Red, 4'-methylthioazobenzene, and thiazole orange) on D
      threoninols (threoninol nucleotides) at the center of their strands. NMR
      spectroscopic analyses revealed that two dyes from each strand were axially
      stacked in an antiparallel manner to each other in the duplex, and were located
      adjacent to the 3'-side of a natural nucleobase. Interestingly, this positional
      relationship of the dyes was completely the opposite of that assembled in DNA
      that we reported previously: dyes in DNA were located adjacent to the 5'-side of
      a natural nucleobase. This observation was also consistent with the circular
      dichroism of dimerized dyes in which the Cotton effect of the dyes (i.e., the
      winding properties of two dyes) was inverted in RNA relative to that in DNA.
      Further spectroscopic analyses revealed that clustering of the dyes on RNA
      duplexes induced distinct hypsochromicity and narrowing of the band, thus
      demonstrating that the dyes were axially stacked (i.e., H-aggregates) even on an
      A-type helix. On the basis of these results, we also prepared heterodimers of a
      fluorophore (thiazole orange) and quencher (Methyl Red) in an RNA duplex.
      Fluorescence from thiazole orange was found to be strongly quenched by Methyl Red
      due to the excitonic interaction, so that the ratio of fluorescent intensities of
      the RNA-thiazole orange conjugate with and without its complementary strand
      carrying a quencher became as high as 27. We believe that these RNA-dye
      conjugates are potentially useful probes for real-time monitoring of RNA
      interference (RNAi) mechanisms.

PMID- 22996356
TI  - Quercetin reduces oxidative damage induced by paraquat via modulating expression
      of antioxidant genes in A549 cells.
AB  - Oxidative injury can occur in the lung through the generation of reactive oxygen
      species (ROS) via redox cycling owing to intentional or accidental ingestion of
      paraquat (PQ), a common herbicide. A wide array of phytochemicals has been shown
      to reduce cellular oxidative damage by modulating cytoprotective genes.
      Quercetin, a well-known flavonoid, has been reported to display cytoprotective
      effects by up-regulating certain cytoprotective genes. In this context, we
      investigated the effect of quercetin on PQ-induced cytotoxicity in alveolar A549
      cells, modulation of antioxidant genes, activation of transcription factor-Nrf2
      and its target HO-1 expression. Quercetin reduced PQ-induced cytotoxicity in A549
      cells that was evaluated by both 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl
      tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Modulation of
      antioxidant genes was compared when cells were treated with PQ, quercetin and
      both using qRT-PCR. Activation of transcription factor-Nrf2 and induction of its
      target gene, HO-1 was demonstrated by western blot analysis. A remarkable
      reduction in the ROS level as well as an increase in the total cellular
      glutathione (GSH) level occurred when PQ-exposed cells were treated with
      quercetin. Our findings suggest that quercetin may be used to mitigate or
      minimize oxidative stress via reducing the generation of ROS.

PMID- 22996357
TI  - A watershed in clinical outcomes of human infections with highly pathogenic H5N1
      avian influenza viruses: lessons from case-management in Egypt.

PMID- 22996358
TI  - [Morbidity and mortality in HIV infection].
AB  - Combination antiretroviral therapy (cART) has dramatically improved the prognosis
      of HIV-infected individuals, with a close to a normal life expectancy in a
      significant proportion of treated individuals. Upon start of cART, HIV-induced
      immune deficiency can be prevented or, if already present, reconstituted.
      Remaining morbidity and mortality is partly due to the late diagnosis of HIV
      infection or late presentation of patients, when CD4-T-cells have already fallen
      below 200 cells/ul and/or AIDS-defining conditions have manifested. Further
      reasons for remaining morbidity and mortality are related to co-morbidities such
      as viral hepatitis and tumors, particularly in older patients. As HIV-infected
      patients become older, increasing co-morbidities and socio-economic costs may
      become a challenge in the future.

PMID- 22996359
TI  - [Hyperthyroidism, eosinophilia, and fever in a 64-year-old patient].
AB  - We report on a male patient suffering from loss of weight, fatigue, fever,
      eosinophilia, and hyperthyreoidism. The echocardiogram revealed a left atrial
      mass originating from the posterior mitral leaflet. In combination with the
      constitutional symptoms a left atrial myxoma was diagnosed. The tumor was
      surgically removed. Postoperatively therapy with corticosteroids and thiamazole
      was stopped. During follow-up, eosinophilia and hyperthyreodism could no longer
      be detected.

PMID- 22996360
TI  - Does combined open and arthroscopic synovectomy for diffuse PVNS of the knee
      improve recurrence rates?
AB  - BACKGROUND: Diffuse-type pigmented villonodular synovitis (PVNS) has a high local
      recurrence rate and as such can lead to erosive destruction of the involved
      joint. Multiple surgical modalities exist, but it is unknown which technique best
      minimizes local recurrence and surgical morbidity. QUESTIONS/PURPOSES: We
      compared recurrence rates, arthritis progression, and complications between
      arthroscopic and open modalities for diffuse PVNS of the knee. METHODS: We
      retrospectively identified 103 patients with PVNS treated between 1993 and 2011.
      Of these, 48 had diffuse-type PVNS of the knee treated by all-arthroscopic, open
      posterior with arthroscopic anterior, or open anterior and open posterior
      synovectomy. We recorded patient demographics, treatment profiles, recurrence
      rates, and arthritic progression. Minimum followup was 3 months (median, 40
      months; range, 3-187 months). RESULTS: Recurrence rates were lower in the
      open/arthroscopic group compared with the arthroscopic or open/open groups: 9%
      versus 62% versus 64%, respectively. Arthritic progression occurred in 17% of the
      total study group with 8% going onto total knee arthroplasty within the followup
      period. We detected no difference between groups with regard to arthritic
      progression or progression to arthroplasty. The most common complication was
      hemarthrosis, which we drained in three patients (6% of the total study group),
      but there were no detectable differences between groups. CONCLUSION: Open
      posterior with arthroscopic anterior synovectomy is a viable, comprehensive
      approach to diffuse PVNS of the knee and provides both low recurrence rates and a
      low postoperative complication profile. Greater numbers of recurrences may be
      partially explained in the arthroscopic group by technical challenges associated
      with posterior arthroscopic synovectomy and in the open/open group by selection
      bias toward more aggressive disease. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 22996361
TI  - 3-D CT is the most reliable imaging modality when quantifying glenoid bone loss.
AB  - BACKGROUND: Posttraumatic anterior shoulder instability is associated with
      anterior glenoid bone loss, contributing to recurrence. Accurate preoperative
      quantification of bone loss is paramount to avoid failure of a soft tissue
      stabilization procedure as bone reconstruction is recommended for glenoid defects
      greater than 20% to 27%. QUESTIONS/PURPOSES: We determined whether radiography,
      MRI, or CT was most reliable to quantify glenoid bone loss in recurrent anterior
      shoulder instability. METHODS: Seven intact fresh-frozen human cadaveric
      shoulders were imaged with radiography, MRI, CT, and three-dimensional (3-D) CT.
      Three sequential anterior glenoid defects then were created, measured, and the
      shoulders reimaged after each defect. Defect sizes were less than 12%, 12% to
      25%, and 25% to 40%. The gold standard measurement was determined by comparing
      measurements taken on the cadaver by two surgeons using digital calipers with the
      measurements determined by using electronic digital calipers on the 3-D CT. This
      measurement was used for comparison of all estimations by the evaluators. Twelve
      independent blinded evaluators reviewed the 112 image sets and estimated the
      percent of glenoid bone loss. Images were scrambled and rereviewed by the same
      observers 2 months later to determine intraobserver reliability. We determined
      reliability with kappa values. RESULTS: Kappa values between predicted bone loss
      versus true loss (determined by our gold standard measurements) across all 12
      raters for each modality were: 3-D CT, 0.50; CT, 0.40; MRI, 0.27; and
      radiographs, 0.15. Interobserver agreement (kappa) values were: 3-D CT, 0.54; CT,
      0.47; MRI, 0.31; and radiographs, 0.15. The intraobserver agreement (kappa)
      values were: 3-D CT, 0.59; CT, 0.64; MRI, 0.51; and radiographs, 0.45.
      CONCLUSIONS: Three-dimensional CT was the most reliable imaging modality for
      predicting glenoid bone loss. Regular CT was the second most reliable and
      reproducible modality.

PMID- 22996362
TI  - Does a kinematically aligned total knee arthroplasty restore function without
      failure regardless of alignment category?
AB  - BACKGROUND: Kinematically aligned TKA restores function by aligning the femoral
      and tibial components to the normal or prearthritic joint lines of the knee.
      However, aligning the components to the joint lines of the normal knee also
      aligns the tibial component in varus, creating concern that varus alignment might
      result in poor function and early catastrophic failure. QUESTIONS/PURPOSES: We
      therefore determined whether function and the incidence of catastrophic failure
      were different when the tibial component, knee, and limb alignment were in a
      specified normal range, varus outlier, or valgus outlier. METHODS: We
      prospectively followed all 198 patients (214 knees) who underwent TKAs between
      February and October 2008. We treated each knee in this cohort of patients with a
      kinematically aligned, cruciate-retaining prosthesis implanted using patient
      specific guides. From a long-leg scanogram, we measured and categorized alignment
      of the tibial component as in range (<= 0 degrees ) or a varus outlier (> 0
      degrees ), alignment of the knee as in range (between -2.5 degrees  to -7.4
      degrees  valgus) or a varus (> -2.5 degrees ) or valgus (< -7.4 degrees )
      outlier, and alignment of the limb as in range (0 degrees  +/- 3 degrees ) or a
      varus (> 3 degrees ) or valgus (< -3 degrees ) outlier. We assessed function
      using the Oxford Knee Score and WOMAC score, and reported catastrophic failure as
      the incidence of revision attributable to loosening, wear, and instability of the
      femoral or tibial components. The minimum followup was 31 months (mean, 38
      months; range, 31-43 months). RESULTS: The mean Oxford Knee Score of 43 and WOMAC
      score of 92 were similar between the three alignment categories. The incidence of
      catastrophic failure in each alignment category was zero. CONCLUSIONS:
      Kinematically aligned TKA restores function without catastrophic failure
      regardless of the alignment category. Because 75% of patients had their tibial
      component categorized as a varus outlier and also had high function and a zero
      incidence of catastrophic failure, the concern that kinematic alignment
      compromises function and places the components at a high risk for catastrophic
      failure is unfounded and should be of interest to surgeons committed to cutting
      the tibia perpendicular to the mechanical axis of the tibia. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22996363
TI  - Grazing and detritivory in 20 stream food webs across a broad pH gradient.
AB  - Acidity is a major driving variable in the ecology of fresh waters, and we sought
      to quantify macroecological patterns in stream food webs across a wide pH
      gradient. We postulated that a few generalist herbivore-detritivores would
      dominate the invertebrate assemblage at low pH, with more specialists grazers at
      high pH. We also expected a switch towards algae in the diet of all primary
      consumers as the pH increased. For 20 stream food webs across the British Isles,
      spanning pH 5.0-8.4 (the acid sites being at least partially culturally
      acidified), we characterised basal resources and primary consumers, using both
      gut contents analysis and stable isotopes to study resource use by the latter. We
      found considerable species turnover across the pH gradient, with generalist
      herbivore-detritivores dominating the primary consumer assemblage at low pH and
      maintaining grazing. These were joined or replaced at higher pH by a suite of
      specialist grazers, while many taxa that persisted across the pH gradient
      broadened the range of algae consumed as acidity declined and increased their
      ingestion of biofilm, whose nutritional quality was higher than that of coarse
      detritus. There was thus an increased overall reliance on algae at higher pH,
      both by generalist herbivore-detritivores and due to the presence of specialist
      grazers, although detritus was important even in non-acidic streams. Both the
      ability of acid-tolerant, herbivore-detritivores to exploit both autochthonous
      and allochthonous food and the low nutritional value of basal resources might
      render chemically recovering systems resistant to invasion by the specialist
      grazers and help explain the sluggish ecological recovery of fresh waters whose
      water chemistry has ameliorated.

PMID- 22996364
TI  - A major player "gets in the act".

PMID- 22996365
TI  - Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis
      mediated by human gammadelta T cells.
AB  - Neuroblastoma is the most common extracranial solid tumor in children that is
      refractory to intensive multimodal therapy. In particular, tumor-initiating cells
      (TICs) derived from neuroblastoma are believed responsible for tumor formation
      and resistance to the conventional therapy; an optimal strategy therefore should
      target this population. Technically, TICs can be enriched from neuroblastoma
      derived spheres when the tumor cells are cultured in a serum-free medium
      supplemented with certain growth factors. Recently, a line of evidence has
      suggested antitumor potential of Vgamma9Vdelta2 T cells (gammadelta T cells), a T
      cell population that recognizes and kills target cells independent of surface HLA
      expressions. Furthermore, a mevalonate pathway inhibitor, zoledronate, has been
      reported to enhance cytolytic activity of gammadelta T cells. On the basis of
      these findings, we hypothesized that zoledronate would sensitize neuroblastoma
      TICs to gammadelta T-cell-mediated cytolysis and promote therapeutic efficacy
      against neuroblastoma. In the current study, we show that zoledronate efficiently
      sensitizes both neuroblastoma-derived adherent cells and sphere-forming cells to
      gammadelta T-cell-mediated cytolysis. Subsequently, in vitro colony formation
      inhibition assay and in vivo animal studies reveal that the presence of
      gammadelta T cells decelerates outgrowth of neuroblastoma TICs. We finally show
      that addition of interleukin-15 and/or interleukin-18 in culture enhances the
      cytolytic activity of gammadelta T cells. On the basis of these data, we conclude
      that ex vivo expanded gammadelta T cells are a promising tool for
      antineuroblastoma immunotherapy with options for further improvement.

PMID- 22996366
TI  - Improvement of antitumor effect of intratumoral injection of immature dendritic
      cells into irradiated tumor by cyclophosphamide in mouse colon cancer model.
AB  - Recently, chemotherapy and radiotherapy are known to directly affect some
      immunosuppressive barriers within a tumor microenviroment. We used
      cyclophosphamide (CTX), which is known to enhance the immune response by
      suppressing CD4+CD25+ regulatory T cells (Treg cells) when used at a low dose, as
      a chemotherapeutic agent to provide a synergic effect in the irradiation and
      dendritic cells (DC) combination therapy. Some previous studies observed that a
      single-dose CTX treatment significantly reduced the number of Treg cells in 3-5
      days, however, the reduced Treg cells increased rapidly after 5 days. To overcome
      the disadvantages of a single-dose CTX, we used 30 mg/kg dose of CTX, which was
      treated intraperitoneally to mice 3 days before every immature DC (iDC) injection
      (known as "metronomic schedule CTX"). Irradiation was applied at a dose of 10 Gy
      to the tumor on the right thigh by a linear accelerator. Then, iDC was
      intratumorally injected into the irradiated tumor site. Growth of a distant tumor
      on the right and left flank was suppressed by an injection of iDC into the
      irradiated tumor, and this effect was increased by the metronomic schedule CTX.
      Also, combinations treated with the metronomic schedule CTX and ionizing
      radiation (IR)/iDC, showed the longest survival time compared with other groups.
      This antitumor immune response of IR/iDC was improved by metronomic schedule CTX
      and this result was associated with decreasing the proportion of CD4+CD25+ Treg
      cells and increasing the number of tumor-specific interferon-gamma-secreting T
      cells. Our results demonstrated that metronomic schedule CTX improves the
      antitumor effect of immunization with an injection of DC s into the irradiated
      tumor.

PMID- 22996367
TI  - Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after
      lymphopenia induction for metastatic melanoma.
AB  - A single-institution pilot clinical trial was performed combining
      nonmyeloablative chemotherapy and the adoptive transfer of tumor-infiltrating
      lymphocytes with interleukin-2 in patients with metastatic melanoma. Nineteen
      patients were enrolled with 13 patients (68%) successfully completing treatment.
      An overall response rate (partial and complete responses) of 26% by intention to
      treat was achieved with a median follow-up time of 10 months. Of the 13 treated
      patients, there were 2 complete responses and 3 partial responses (38% response
      rate among treated patients), along with 4 patients with stable disease ranging
      from 2+ to 24+months. Three of the 4 patients with stable disease have had
      disease control without additional therapy, including one at 24+ months. Adoptive
      therapy with infiltrating lymphocytes is labor intensive but feasible and has a
      high response rate in treated patients.

PMID- 22996368
TI  - Effective treatment of refractory CMV reactivation after allogeneic stem cell
      transplantation with in vitro-generated CMV pp65-specific CD8+ T-cell lines.
AB  - To treat patients with refractory cytomegalovirus (CMV) reactivation after
      allogeneic stem cell transplantation, a phase I/II clinical study on adoptive
      transfer of in vitro-generated donor-derived or patient-derived CMV pp65-specific
      CD8* T-cell lines was performed. Peripheral blood mononuclear cells from CMV
      seropositive donors or patients were stimulated with HLA-A*0201-restricted and/or
      HLA-B*0702-restricted CMV pp65 peptides (NLV/TPR) and 1 day after stimulation
      interferon-gamma)-producing cells were enriched using the CliniMACS Cytokine
      Capture System (interferon-gamma), and cultured with autologous feeders and low
      dose interluekin-2. After 7-14 days of culture, quality controls were performed
      and the CMV-specific T-cell lines were administered or cryopreserved. The T-cell
      lines generated contained 0.6-17 * 10(6) cells, comprising 54%-96% CMV pp65
      specific CD8 T cells, and showed CMV-specific lysis of target cells. Fifteen CMV
      specific T-cell lines were generated of which 8 were administered to patients
      with refractory CMV reactivation. After administration, no acute adverse events
      and no graft versus host disease were observed and CMV load disappeared. In
      several patients, a direct relation between administration of the T-cell line and
      the in vivo appearance of CMV pp65-specific T cells could be documented. In
      conclusion, administration of CMV pp65-specific CD8* T-cell lines was found to be
      feasible and safe, and enduring efficacy of administered CMV pp65-specific CD8* T
      cell lines could be demonstrated.

PMID- 22996369
TI  - Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in
      subjects with adenocarcinoma of the pancreas.
AB  - Baseline levels of innate and adaptive immune cell functions were studied in
      patients with pancreatic cancer. The effects of pemetrexed were measured at 7 and
      14 days after initial therapy then 14 days after combination therapy with
      gemcitabine. Pretherapy levels of absolute numbers of natural killer (NK) cells
      positively correlated with survival. Cytolytic units of NK activity correlated
      positively with NK cell numbers. Pemetrexed decreased NK cytolytic units to
      significance when combined with gemcitabine. Pemetrexed increased intracellular
      accumulation of interferon gamma (IFNgamma) in NK cells that correlated
      negatively with survival. Addition of gemcitabine decreased IFNgamma-producing NK
      cells to baseline. Memory (CD45RO*) T cells enumerated at baseline correlated
      negatively with survival but were decreased by pemetrexed therapy. Memory T cells
      were increased in subjects with greater B7-H3 expression in tumor tissue, whereas
      OX40*-activated total T cells and helper T-cell subset were decreased. FoxP3*,
      CD8* T cells correlated positively with progression-free interval and survival.
      In conclusion, innate NK-cell immunity and FoxP3*, CD8* T cells seemed beneficial
      to pancreatic cancer patients. Higher levels of B7-H3 expression in pancreatic
      tumors were detrimental to effective immunity. Although pemetrexed therapy
      increased activation of a subset of NK cells to produce IFNgamma, addition of
      gemcitabine abated those responses, decreasing IFNgamma-producing NK cells,
      whereas NK cells producing interleukin-2 without IFNgamma at this timepoint
      positively correlated with survival. Innate immunity and adaptive immunity thus
      are important in defense against pancreatic cancer. Progression-free interval and
      survival were longer than observed in a phase III trial where gemcitabine
      preceded pemetrexed suggesting that a larger trial of pemetrexed preceding
      gemcitabine is warranted.

PMID- 22996370
TI  - Tumor stem cell antigens as consolidative active specific immunotherapy: a
      randomized phase II trial of dendritic cells versus tumor cells in patients with
      metastatic melanoma.
AB  - Only 10% of metastatic melanoma patients survive 5 years, even though many can
      achieve substantial tumor reduction by surgical resection and/or radiation
      therapy and/or systemic therapy. An effective, nontoxic, consolidation
      immunotherapy could benefit such patients. We initiated a randomized trial to
      compare 2 promising patient-specific immunotherapy cell products. Patients had to
      have a diagnosis of metastatic melanoma and availability of an autologous
      melanoma cell line. Patients were stratified by whether their most advanced stage
      had been regional or distant metastases, and by whether they had measurable
      disease at the time of treatment, then they were randomized to receive irradiated
      autologous proliferating tumor cells or autologous dendritic cells (DC) loaded
      with antigens from such cells. Both products were injected subcutaneously in 500
      ug of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and
      then monthly for 5 months. Patients in the 2 arms did not differ in baseline
      characteristics. All patients received prescribed therapy. Treatment was well
      tolerated. At the time of initial analysis, with no patients lost to follow-up,
      50% of patients deceased, and all surviving patients followed for at least 6
      months after randomization, survival is superior in the DC arm (hazard ratio,
      0.27; 95% confidence interval, 0.098-0.729) with median survival not reached
      versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This
      trial provides evidence that a DC vaccine is associated with longer survival
      compared with a tumor cell vaccine, and is consistent with previous data
      suggesting a survival benefit from this patient-specific immunotherapy.

PMID- 22996371
TI  - Inhibition of RelA-Ser536 phosphorylation by a competing peptide reduces mouse
      liver fibrosis without blocking the innate immune response.
AB  - Phosphorylation of the RelA subunit at serine 536 (RelA-P-Ser536) is important
      for hepatic myofibroblast survival and is mechanistically implicated in liver
      fibrosis. Here, we show that a cell-permeable competing peptide (P6) functions as
      a specific targeted inhibitor of RelA-P-Ser536 in vivo and exerts an
      antifibrogenic effect in two progressive liver disease models, but does not
      impair hepatic inflammation or innate immune responses after lipopolysaccharide
      challenge. Using kinase assays and western blotting, we confirm that P6 is a
      substrate for the inhibitory kappa B kinases (IKKs), IKKalpha and IKKbeta, and,
      in human hepatic myofibroblasts, P6 prevents RelA-P-Ser536, but does not affect
      IKK activation of IkappaBalpha. We demonstrate that RelA-P-Ser536 is a feature of
      human lung and skin fibroblasts, but not lung epithelial cells, in vitro and is
      present in sclerotic skin and diseased lungs of patients suffering from
      idiopathic pulmonary fibrosis. CONCLUSION: RelA-P-Ser536 may be a core fibrogenic
      regulator of fibroblast phenotype.

PMID- 22996372
TI  - Malignant dermatofibroma: clinicopathological, immunohistochemical, and molecular
      analysis of seven cases.
AB  - Dermatofibroma (cutaneous fibrous histiocytoma) represents a common benign
      mesenchymal tumor, and numerous morphological variants have been described. Some
      variants of dermatofibroma are characterized by an increased risk of local
      recurrences, and there are a few reported metastasizing cases. Unfortunately, an
      aggressive behavior cannot be predicted reliably by morphology at the moment, and
      we evaluated the value of array-comparative genomic hybridization (CGH) in this
      setting. Seven cases of clinically aggressive dermatofibromas were identified,
      and pathological and molecular features were evaluated. The neoplasms occurred in
      four female and in three male patients (mean age was 33 years, range 2-65 years),
      and arose on the shoulder, buttock, temple, lateral neck, thigh, ankle, and
      cheek. The size of the neoplasms ranged from 1 to 9 cm (mean: 3 cm). An
      infiltration of the subcutis was seen in five cases. Two neoplasms were
      completely excised, whereas an incomplete or marginal excision was reported in
      the remaining cases. Local recurrences were seen in six cases (time to the first
      recurrence ranged from 8 months to 9 years). Metastases were noted between 3
      months and 8 years after diagnosis in six patients. Two patients died of disease,
      and two patients are alive with disease. Histologically, the primary tumors
      showed features of cellular dermatofibroma (four cases), cellular/aneurysmal
      dermatofibroma (one case), atypical/cellular dermatofibroma (one case), and
      classical dermatofibroma (one case). Mitotic figures ranged from 3 to 25 per 10
      high-power fields, and focal necrosis was present in five cases. Interestingly,
      malignant transformation from cellular dermatofibroma to an obvious spindle
      cell/pleomorphic sarcoma was seen in one primary and in one recurrent neoplasm.
      Five neoplasms showed chromosomal aberrations by array-CGH, suggesting that these
      changes may represent an additional diagnostic tool in the recognition of cases
      of dermatofibroma with a metastatic potential.

PMID- 22996373
TI  - Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2
      in squamous intraepithelial lesions: potential utility in diagnosis and
      management.
AB  - While cervical cancer screening relies on cervical cytology and high-risk human
      papillomavirus (HPV) detection, the histologic diagnosis, and specifically lesion
      grade, is the main parameter that drives clinical management of screen-positive
      women. Morphologically diagnosed squamous intraepithelial lesions (SIL/CIN)
      regress spontaneously in more than half of the cases, but identifying those
      likely to persist and progress is not currently possible based upon morphology.
      Lack of major capsid protein L1 expression has been suggested as a feature in
      progressive lesions, whereas expression of the minor capsid protein L2 has not
      been extensively evaluated. The goal of this study is to evaluate
      immunohistochemical expression of L1 and L2 in SILs in correlation with lesion
      grade. A total of 150 cervical specimens with SILs were selected based on HPV 16
      or HPV 18 detection by Q-PCR. These included 89 low-grade SILs (LSIL/CIN 1) and
      123 high-grade SILs (75 HSIL/CIN 2 and 48 HSIL/CIN 3). More than one lesion/grade
      was identified in 53 specimens. The presence and grade of SIL was determined by a
      panel of pathologists. Capsid protein expression was assessed by
      immunohistochemistry using MAB 837 for L1 and RG-1 for L2. Lesions of different
      grades in the same specimen were scored separately. Expression of capsid proteins
      was detected in 34/89 (40%) LSIL/CIN 1, 5/75 (6%) HSIL/CIN 2 and none of 48
      HSIL/CIN 3. L1 and L2 were co-expressed in the same area of the lesion in 22
      cases. In addition, L1 alone was expressed in 6 lesions and L2 alone in 11
      lesions. Among the cases with multiple lesion grades in the same specimen, none
      with HSIL/CIN 3 expressed capsid proteins in any portion/grade of the lesion. HPV
      capsid proteins are expressed almost exclusively in LSIL/CIN 1 and rarely in
      HSIL/CIN 2. Additional studies are warranted to examine lack of L1 and L2
      expression in LSIL/CIN 1 as a predictor of persistence or progression to HSIL/CIN
      3, the precursor of cervical cancer.

PMID- 22996374
TI  - Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21)
      expression in squamous cell carcinoma of the larynx.
AB  - Although a strong etiologic relationship between human papillomavirus (HPV) and a
      majority of oropharyngeal squamous cell carcinomas has been established, the role
      of HPV in non-oropharyngeal head and neck carcinomas is much less clear. Here, we
      investigated the prevalence and clinicopathologic significance of HPV and its
      reported biomarkers, CDKN2A(p16) and CDKN1A(p21), in laryngeal squamous cell
      carcinomas in patients treated either with primary surgery and postoperative
      radiation or with definitive radiation-based therapy. Nearly all of 76 tumors
      were keratinizing and none displayed the nonkeratinizing morphology that is
      typically associated with HPV infection in the oropharynx. However, CDKN2A(p16)
      immunohistochemistry was positive in 21 cases (28%) and CDKN1A(p21) in 34 (45%).
      CDKN2A(p16) and CDKN1A(p21) status strongly correlated with each other
      (P=0.0038). Yet, only four cases were HPV positive by DNA in situ hybridization
      or by reverse transcriptase PCR E6/E7 mRNA (all four were CDKN2A(p16) and
      CDKN1A(p21) positive). Unexpectedly, 9 additional tumors out of 20 CDKN2A(p16)
      positive cases harbored high-risk HPV DNA by PCR. For further investigation of
      this unexpected result, in situ hybridization for E6/E7 mRNA was performed on
      these nine cases and all were negative, confirming the absence of
      transcriptionally active virus. Patients with CDKN1A(p21)-positive tumors did
      have better overall survival (69% at 3 years) than those with CDKN1A(p21)
      negative tumors (51% at 3 years) (P=0.045). There was also a strong trend towards
      better overall survival in the CDKN2A(p16)-positive group (P=0.058). Thus, it
      appears that the role of HPV is more complex in the larynx than in the
      oropharynx, and that CDKN2A(p16) and CDKN1A(p21) expression may not reflect HPV
      driven tumors in most cases. Because of this, CDKN2A(p16) should not be used as a
      definitive surrogate marker of HPV-driven tumors in the larynx.

PMID- 22996375
TI  - The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine.
AB  - The conventional view of gene regulation in biology has centered around protein
      coding genes via the central dogma of DNA-->mRNA-->protein. The discovery of
      thousands of long non-coding RNAs (lncRNAs) has certainly changed our view of the
      complexity of mammalian genomes and transcriptomes, as well as many other aspects
      of biology including transcriptional and posttranscriptional regulation of gene
      expression. Accumulating reports of misregulated lncRNA expression across
      numerous cancer types suggest that aberrant lncRNA expression may be a major
      contributor to tumorigenesis. Here, we summarize recent data about the biological
      characteristics of lncRNAs in cancer pathways. These include examples with a wide
      range of molecular mechanisms involved in gene regulation. We also consider the
      medical implications, and discuss how lncRNAs can be used for cancer diagnosis
      and prognosis, and serve as potential therapeutic targets. As more examples of
      regulation by lncRNA are uncovered, one might predict that the large transcripts
      will eventually rival small RNAs and proteins in their versatility as regulators
      of genetic information.

PMID- 22996376
TI  - Thymidylate synthase expression and molecular alterations in adenosquamous
      carcinoma of the lung.
AB  - Thymidylate synthase expression is known to be higher in squamous cell carcinoma
      than in adenocarcinoma of the lung. It is thought that this is the reason for the
      poor efficacy of pemetrexed in squamous cell carcinoma. However, there is limited
      data on thymidylate synthase expression in adenosquamous carcinoma, a distinct
      subtype of lung cancer containing both squamous and glandular differentiation.
      Furthermore, molecular alterations like epidermal growth factor receptor and
      Kirsten rat sarcoma 2 viral oncogene homolog mutations, which are seen in
      adenocarcinomas, are not well understood in mixed histology tumors such as
      adenosquamous carcinoma. In our study, we sought to better characterize
      adenosquamous tumors of the lung. Using immunohistochemistry to evaluate
      thymidylate synthase protein levels, we found that the expression of thymidylate
      synthase in these mixed tumors roughly parallel that of squamous cell carcinoma,
      instead of falling in between squamous cell and adenocarcinoma. Of note, in
      adenosquamous samples, the expression of thymidylate synthase was more closely
      correlated within the two components than would be expected by random chance
      alone. Also, we had a relatively high rate of epidermal growth factor receptor
      (11%) and Kirsten rat sarcoma 2 viral oncogene homolog (33%) mutations in these
      specimens, with the mutations showing convergence in both the glandular and
      squamous components upon microdissection. Our results indicate that adenosquamous
      carcinomas are not simple mixtures of their two histological components; they
      rather behave as their own entity, and it is important to further understand
      their behavior. Given the similarity of thymidylate synthase expression between
      squamous cell and adenosquamous carcinoma, and that thymidylate synthase is the
      main target of pemetrexed, we extrapolate that pemetrexed may also have inferior
      clinical activity in adenosquamous carcinoma.

PMID- 22996377
TI  - Prognostic significance and function of phosphorylated ribosomal protein S6 in
      esophageal squamous cell carcinoma.
AB  - Ribosomal protein S6 is a key regulator of 40S ribosome biogenesis, and its
      phosphorylation is closely related to cell growth capacity. However, as a
      downstream target of S6 kinases, the clinical significance and the roles of S6
      and S6 phosphorylation in cell viability and motility of esophageal squamous cell
      carcinoma remain unclear. Here, we show that high level of phosphorylated
      ribosomal protein S6 (p-S6) (immunohistochemistry score >=5) and an increased
      ratio of p-S6/S6 (immunohistochemistry score >=0.75) were significantly
      associated with shortened disease-free survival in patients with esophageal
      squamous cell carcinoma in univariate analysis (P=0.049 and P<0.001,
      respectively). After adjusting for age, tumor-nodes-metastasis stage,
      chemotherapy, and radiation therapy in multivariate analysis, both p-S6 (hazard
      ratio 2.21, P=0.005) and p-S6/S6 (hazard ratio 2.40, P<0.001) remained
      independent adverse prognostic factors. In addition, S6 and S6 kinase 1 knockdown
      resulted in attenuation of viability by suppressing cyclin D1 expression in
      esophageal cancer cells. Furthermore, depletion of S6 and S6 kinase 1 resulted in
      a reduction in esophageal cancer cell migration and invasion. This was paralleled
      by a reduction in focal adhesion and by suppression of extracellular signal
      regulated kinase and c-jun N-terminal kinase phosphorylation, which control cell
      motility. Collectively, these findings suggest that p-S6 and the ratio of p-S6/S6
      are closely relevant to tumor progression and have prognostic significance in
      esophageal squamous cell carcinoma.

PMID- 22996378
TI  - Enhancing the sensitivity of aptameric detection of lysozyme with a "feed
      forward" network of DNA-related reaction cycles.
AB  - In this study, a network of DNA-related reaction cycles was established to
      enhance the sensitivity of lysozyme detection with dual signal amplification, and
      aptamer-based reactions were integrated into this system to provide high
      specificity. The network was organized in a feed-forward manner: the "upstream
      cycles" recognized the lysozyme (the target) and released the "messenger strands"
      from probe A (a DNA construct); the "downstream cycles" received them and then
      released the "signal strands" from another DNA construct, probe B, in multiplied
      quantities to that of the original inputted lysozyme. The upstream cycles
      centered on "target-displacement polymerization", which circulates the lysozyme
      to provide primary amplification; the downstream cycles centered on "strand
      displacement polymerization", which circulates the messenger strand to provide
      further amplification. There were also several "nicking-polymerization" cycles in
      both reaction groups that provide extra signal amplification. In total, the
      network enclosed eight interconnected and autonomic reaction cycles, with only
      two probes, two primers, and two enzymes needed as raw feeds, and the network can
      be operated simply in one-pot mode. With this network, lysozyme could be
      quantified at lysozyme concentrations as low as 2.0*10(-14) M, with a detection
      limit of 3.6*10(-15) M (3sigma rule), which was seven orders of magnitude lower
      than that obtained without any amplification(1.8*10(-8) M). Detection of lysozyme
      in real serum samples confirmed the reliability and practicality of the assay
      based on this reported reaction network.

PMID- 22996379
TI  - Simulating the properties of small pore silica zeolites using interatomic
      potentials.
AB  - Despite the sustained use of forcefield methodologies to study SiO(2) polymorphs
      few reviews on the subject are available in the literature. The present study is
      an attempt to help fill this gap, focusing on classical forcefields used to
      reproduce and predict properties of pure silica zeolites (or zeosils) such as
      cell parameters, SiO distance and especially pore size. Instead of an exhaustive
      study we have focused on an application where diffusion of hydrocarbons makes
      important the use of pure silica zeolites. A particular area of interest is small
      pore zeosils containing 8-rings as the largest window, which are industrially
      interesting for their ability to perform kinetic separations of mixtures of C3
      hydrocarbon molecules whose dimensions are of similar characteristics. A set of
      forcefields have been selected from the literature to analyze their accuracy and
      transferability when predicting structural, mechanical and dynamical properties
      of small pore pure silica zeolites and their performance at selective diffusion
      of C3 hydrocarbons.

PMID- 22996380
TI  - Men's controlling behaviors and women's experiences of physical violence in
      Malawi.
AB  - In the feminist paradigm, intimate partner violence (IPV) among heterosexual
      couples is gender asymmetric and largely a tactic of male control. However,
      research on the relationship between men's controlling behavior and physical
      violence against women is limited. This study examines whether having a
      controlling partner is associated with women's reports of experiencing physical
      violence in Malawi. Bivariate and multivariate analyses were conducted using data
      from 8,385 women who completed the domestic violence module of the Malawi 2004
      Demographic and Health Survey. About 18 % of women reported they had experienced
      moderately severe physical violence and 1 % experienced very severe violence in
      the past 12 months. A third of women reported their partners had ever been
      controlling. Results from multivariable ordinal logistic regression showed that
      women who had controlling partners were significantly more likely to report
      experiencing physical violence. Other factors significantly associated with
      women's experience of physical violence included women who reported initiating
      physical violence against their partners, women's work status, partners' lower
      education level, and partners' alcohol consumption. Women with controlling
      partners were at increased risk of experiencing physical violence in the past
      year. However, women who reported initiating physical violence in the past year
      were nearly four times more likely to experience partner violence in the same
      time period. Future research should attempt to elucidate these two important risk
      factors for IPV. 

PMID- 22996382
TI  - Antimicrobial prophylaxis for surgery.

PMID- 22996381
TI  - Molecular mechanisms of curcumin action: gene expression.
AB  - Curcumin derived from the tropical plant Curcuma longa has a long history of use
      as a dietary agent, food preservative, and in traditional Asian medicine. It has
      been used for centuries to treat biliary disorders, anorexia, cough, diabetic
      wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and
      therapeutic properties of curcumin are associated with its antioxidant, anti
      inflammatory, and anticancer properties. Extensive research over several decades
      has attempted to identify the molecular mechanisms of curcumin action. Curcumin
      modulates numerous molecular targets by altering their gene expression, signaling
      pathways, or through direct interaction. Curcumin regulates the expression of
      inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF),
      growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9,
      MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis
      related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g.,
      cyclin D1). Curcumin modulates the activity of several transcription factors
      (e.g., NF-kappaB, AP-1, STAT) and their signaling pathways. Based on its ability
      to affect multiple targets, curcumin has the potential for the prevention and
      treatment of various diseases including cancers, arthritis, allergies,
      atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity,
      diabetes, psoriasis, and autoimmune diseases. This review summarizes the
      molecular mechanisms of modulation of gene expression by curcumin.

PMID- 22996383
TI  - Alterations of signaling pathways in muscle tissues of patients with amyotrophic
      lateral sclerosis.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the
      central nervous system, manifests as progressive weakening of muscles. The
      diagnosis and prognosis of ALS are often unclear, so useful biomarkers are
      needed. METHODS: Total proteins were extracted from muscle samples from 36 ALS,
      17 spinal muscular atrophy (SMA), and 36 normal individuals. The expression
      levels of 134 proteins and phosphoproteins were assessed using protein pathway
      array analysis. RESULTS: Seventeen proteins were differentially expressed between
      ALS and normal muscle, and 9 proteins were differentially expressed between ALS
      and SMA muscle. The low-level expression of Akt and Factor XIIIB correlates with
      unfavorable survival, and the risk score calculated based on these proteins
      predicts the survival of each individual patient. CONCLUSIONS: Some proteins
      could be selected as clinically useful biomarkers. Specifically, Akt and Factor
      XIIIB were found to be promising biomarkers for estimating prognosis in ALS.

PMID- 22996384
TI  - Severe anaphylaxis caused by orally administered vancomycin to a patient with
      Clostridium difficile infection.
AB  - We report the first case of anaphylaxis to oral vancomycin in a cystic fibrosis
      patient with severe and relapsing Clostridium difficile infection (CDI)
      refractory to metronidazole. The patient's colitis has been successfully treated
      with a combination of intravenous metronidazole and tigecycline.

PMID- 22996385
TI  - Toxocara encephalitis presenting with autonomous nervous system involvement.
AB  - Human toxocariasis has been reported to cause a broad spectrum of neurological
      syndromes, including encephalitis, meningitis and meningo-radiculitis.
      Nevertheless, cerebral infection by Toxocara may go undiagnosed due to its
      rarity, elusive symptoms and lack of availability of appropriate testing. We
      report the case of a 54-year-old man who presented with abdominal pain and
      paralytic ileus approximately 3 weeks after having eaten raw snails (a folk
      remedy for peptic ulcer). Three weeks later, marked eosinophilia ensued,
      associated with mental clouding, nystagmus, diplopia, peripheral limbs ataxia,
      urinary retention, slackened deep tendon reflexes, arthralgias and myalgias.
      Cerebrospinal fluid (CSF) examination demonstrated an eosinophilic meningitis,
      and Toxocara canis cerebral infection was diagnosed by positive serology and by
      the detection of T. canis DNA in the CSF. The patient made a full recovery
      following treatment with albendazole and corticosteroids. Physicians should be
      aware of this rare presentation of toxocariasis, whose diagnosis is, today,
      facilitated by molecular biology techniques. A history of ingestion of raw snails
      may alert the clinician to consider the possibility of such an uncommon
      condition.

PMID- 22996386
TI  - IL-18 associates to microvesicles shed from human macrophages by a LPS/TLR-4
      independent mechanism in response to P2X receptor stimulation.
AB  - Extracellular ATP, released upon microbial infection, cell damage, or
      inflammation, acts as an alert signal toward immune cells by activating P2
      receptors. The nucleotide causes microvesicle (MV) shedding from immune and
      nonimmune cells. Here, we show that IL-18 associates with MVs shed by human ex
      vivo macrophages upon P2X receptor stimulation. MV shedding was potently induced
      by ATP and by the P2X7 agonist 3'-benzoylbenzoyl adenosine 5'-triphosphate, while
      it was greatly reduced by P2X irreversible inhibitor-oxidized ATP and by the
      specific P2X7 inhibitors KN-62, A-740003, and A-438079. Peculiarly, the P2X7
      subtype was highly present in the MVs, while on the contrary the P2X3 and P2X4
      subtypes were almost absent. The Ca(2+) ionophore A23187 mimicked the effect of
      3'-benzoylbenzoyl adenosine 5'-triphosphate suggesting that an intracellular
      Ca(2+) increase was sufficient to evoke MV shedding. Caspase inhibitors Ac-YVAD
      CMK or Z-YVAD-CMK did not block the cleavage of MV-associated pro-IL-18. Pro-IL
      18 formation in macrophages did not require pretreatment of cells with LPS, as
      the procytokine was already present in unprimed macrophages and did not decrease
      by incubating cells with the LPS-binding antibiotic polymyxin B nor with the TLR
      4 intracellular inhibitor CLI-095. These data reveal a nucleotide-based mechanism
      responsible for the shedding of MV to which IL-18 is associated.

PMID- 22996388
TI  - "Organo-metal" synergistic catalysis: the 1+1>2 effect for the construction of
      spirocyclopentene oxindoles.
AB  - Synergy in action: a highly efficient "organo-metal" synergistic catalysis
      strategy for the synthesis of spirocyclopentene oxindole derivatives has been
      developed. The lower overall d.r. and ee obtained from the stepwise approach (4:1
      vs. 8:1 d.r.; 71 vs. >99 % ee) suggest that both catalysts function more
      efficiently when combined, compared with the separate catalytic approach, and
      show an evident 1+1>2 synergistic effect for the construction of
      spirocyclopentene oxindoles.

PMID- 22996387
TI  - Trichosporon vanderwaltii sp. nov., an asexual basidiomycetous yeast isolated
      from soil and beetles.
AB  - During a survey of unidentified yeast isolates deposited in the UNESCO-MIRCEN
      Biotechnological Yeast Culture Collection housed at the Department of Microbial,
      Biochemical and Food Biotechnology of the University of the Free State, one
      isolate obtained from soil in South Africa showed 100 % identity in D1/D2 rDNA
      sequence with undescribed basidiomycetous yeasts isolated from the gut of beetles
      from the United States of America and forest soil from Taiwan in the NCBI
      sequence database. Phylogenetic analyses using sequences of the D1/D2 rDNA and
      ITS regions indicated that all these isolates form a well-supported sub-clade
      that is the sister clade to the Brassicae plus Porosum clades of Trichosporon in
      the order Trichosporonales. Subsequent phenotypic tests revealed that asexual
      reproduction by budding is rare but dominated by arthroconidia resulting from
      segmentation of hyphae and that fusiform giant cells are characterized by budding
      from a broad base. These findings further suggest that these isolates belong to a
      single tremellomycetous yeast species for which the name Trichosporon
      vanderwaltii CBS 12124(T) (=NRRL Y-48732(T), =UOFS Y-1920(T)) is proposed.

PMID- 22996389
TI  - Dissociation of c-Met phosphotyrosine sites in human cells in response to mouse
      hepatocyte growth factor but not human hepatocyte growth factor: the possible
      roles of different amino acids in different species.
AB  - Hepatocyte growth factor (HGF) is essential for embryogenesis, tissue
      regeneration and tumour malignancy through the activation of its receptor, c-Met.
      We previously demonstrated that HGF alpha-chain hairpin-loop, K1 domain and beta
      chain are required for c-Met signalling. The sequential phosphorylation of
      tyrosine residues, from c-Met kinase domain to multidocking regions, is required
      for HGF-signalling transduction. Herein, we provide evidence that the
      disconcerted activation of c-Met tyrosine regions fails to induce biological
      functions. When human cells were incubated with 'mouse HGF', kinase domain
      activation (i.e. phospho-Tyr-1230/34/35) became evident, but the multidocking
      site (i.e. Tyr-1349) was not phosphorylated, resulting in unsuccessful induction
      of migration and mitogenesis. The binding ability of mouse HGF alpha-chain, or of
      beta-chain, to human c-Met was lower than that of human HGF, as evidenced by HGF
      chimera assay. Notably, only four amino acid positions in HGF alpha-chain hairpin
      loop and K1 domain and six positions in beta-chain differed between human HGF and
      mouse HGF. The human-specific amino acids (such as Gln-95 in hairpin-loop, Arg
      134 in K1 domain and Cys-561 in beta-chain) may be important for accurate c-Met
      assembly and signalling transduction.

PMID- 22996390
TI  - Modified cine inversion recovery pulse sequence for the quantification of
      myocardial T1 and gadolinium partition coefficient.
AB  - PURPOSE: To optimize and validate a modified cine inversion recovery sequence
      (MCine-IR) for myocardial T1 quantification and gadolinium partition coefficient
      (lambda(Gd)) estimation at 1.5 T. MATERIALS AND METHODS: The original version of
      the cine inversion recovery sequence was modified to allow fully transverse
      magnetization recovery between two successive inversion pulses. Sixty heart
      phases were acquired from a number of heart cycles determined on a patient heart
      rate basis. Phantom studies were carried out to find the optimal effective TR for
      myocardial and blood pool T1 quantifications in pre- and postcontrast studies.
      Four patients with myocardial infarct (MI) and 22 dilated cardiomyopathy (DCM)
      were investigated, as well as 11 healthy subjects used as controls. RESULTS:
      Effective TR was identified to be 5000 msec and 2000 msec, respectively, for pre-
      and postcontrast studies. A longer precontrast (948 +/- 102 msec) and shorter
      postcontrast (348 +/- 27 msec) T1 in ischemic patients relative to DCM (815 +/-
      98 msec, P = 0.03 and 409 +/- 42 msec, P = 0.001) were noted in delayed
      enhancement (DE) areas. In MI patients lambda(Gd) resulted higher than in DCM in
      DE areas (609 +/- 167 vs. 422 +/- 52, P = 0.01) but lower in segments not
      exhibiting DE (355 +/- 100 vs. 398 +/- 54, P = 0.02). CONCLUSION: It was feasible
      to measure T1 and lambda(Gd) with MCine-IR and the results were in good agreement
      with the literature.

PMID- 22996391
TI  - Role of the C-terminus of Pleurotus eryngii Ery4 laccase in determining enzyme
      structure, catalytic properties and stability.
AB  - The ERY4 laccase gene of Pleurotus eryngii is not biologically active when
      expressed in yeast. To explain this finding, we analysed the role of the C
      terminus of Ery4 protein by producing a number of its different mutant variants.
      Two different categories of ERY4 mutant genes were produced and expressed in
      yeast: (i) mutants carrying C-terminal deletions and (ii) mutants carrying
      different site-specific mutations at their C-terminus. Investigation of the
      catalytic properties of the recombinant enzymes indicated that each novel variant
      acquired different affinities and catalytic activity for various substrates. Our
      results highlight that C-terminal processing is fundamental for Ery4 laccase
      enzymatic activities allowing substrate accessibility to the enzyme catalytic
      core. Apparently, the last 18 amino acids in the C-terminal end of the Ery4
      laccase play a critical role in enzyme activity, stability and kinetic and, in
      particular biochemical and structural data indicate that the K532 residue is
      fundamental for enzyme activation. These studies shed light on the
      structure/function relationships of fungal laccases and will enhance the
      development of biotechnological strategies for the industrial exploitation of
      these enzymes.

PMID- 22996392
TI  - Ecological consistency across space: a synthesis of the ecological aspects of
      Dromiciops gliroides in Argentina and Chile.
AB  - Dromiciops gliroides is an arboreal marsupial found in the temperate forests of
      South America (36-43  degrees S). This species is the sole extant representative
      of the order Microbiotheria, and is a key seed disperser of many native plant
      species, including the keystone mistletoe Tristerix corymbosus. Here, we
      synthesized the current knowledge on the ecological aspects of this species, and
      compared the available information from Argentina and Chile. Population density
      (23 +/- 2 (mean +/- SE) individual/ha) and home range (1.6 +/- 0.6 ha) appear to
      be relatively similar across a marked ecological gradient in the mainland, but
      lower densities (7 +/- 2 individual/ha) and smaller home ranges (0.26 +/- 0.04
      ha) were detected at island sites. We detected regional variation in body
      condition in Chile, but there were no significant differences across a wider E-W
      gradient. Movement patterns fit a random walk model; such behavior might have
      important consequences in shaping plant's spatial patterns. Although our data
      suggest that D. gliroides is more tolerant to habitat disturbance than previously
      thought, its incapability to disperse across non-forested areas suggests that the
      rapid rate of habitat loss and fragmentation that characterizes southern
      temperate forests likely poses a serious threat to this species. These ecological
      similarities are surprising given that forests studied receive dramatically
      different rainfall and correspond to distinct forest types. The evidence
      synthetized here dispels some of the myths about this species but also stresses
      the need for more comprehensive ecological studies across its distribution range.

PMID- 22996393
TI  - Comparison of micro-CT and cone beam CT-based assessments for relative difference
      of grey level distribution in a human mandible.
AB  - OBJECTIVES: The purpose of this study was to examine the ability of CT to assess
      the relative difference of degree of bone mineralization (grey level) parameters
      in a human mandible. METHODS: Ten mandibular sections from cadavers (81.5 +/-
      12.1 years) were scanned using micro-CT with 27.2 MUm voxel size and cone beam CT
      (CBCT) with 200 MUm, 300 MUm, and 400 MUm voxel sizes. In addition, 15 clinical
      CBCT images from young patients (mean age 18.9 +/- 3.3 years) were identified.
      After segmentation of bone voxels, alveolar bone and basal cortical bone regions
      were digitally isolated. A histogram of grey level, which is equivalent to degree
      of bone mineralization, was obtained from each region of the CT images. Mean,
      standard deviation (SD), coefficient of variation (COV), fifth percentile low
      (Low(5)) and high (High(5)) of alveolar bone and basal cortical bone regions were
      obtained. Percentage differences of grey level parameters between alveolar and
      basal cortical bones were computed. RESULTS: The alveolar bone region had
      significantly lower Mean, Low(5) and High(5) values but significantly higher SD
      and COV than the basal cortical bone region for all CT images (p < 0.05). All
      parameters were significantly lower for the old cadaver group than for the young
      patient group (p < 0.05). CONCLUSIONS: CBCT and micro-CT provide comparable
      results in the assessment of relative difference in grey level distribution
      between alveolar and basal cortical bone regions in the human mandible. The
      percentage difference relative to an internal reference (basal cortical bone) can
      be a reliable method when assessing the degree of bone mineralization using CBCT
      images for both cross-sectional and longitudinal comparisons.

PMID- 22996394
TI  - Three-dimensional densitometric analysis of maxillary sutural changes induced by
      rapid maxillary expansion.
AB  - OBJECTIVE: This prospective study evaluated the density of the midpalatal and
      transverse sutures as assessed by low-dose CT before rapid maxillary expansion
      (T0), at the end of active expansion (T1) and after a retention period of 6
      months (T2). METHODS: The study sample comprised 17 pre-pubertal subjects (mean
      age 11.2 years) with constricted maxillary arches. Total amount of expansion was
      7 mm in all subjects. Multislice low-dose CT scans were taken at T0, T1 and T2.
      On the axial CT scanned images six regions of interest (ROIs) were placed along
      the midpalatal and transverse sutures and two in maxillary and palatal bony
      areas. Density was measured in Hounsfield units. Mann-Whitney U test and Friedman
      analysis of variance with post hoc tests were used (p < 0.05). RESULTS: The three
      ROIs in the midpalatal suture showed a significant decrease in density from T0 to
      T1, a significant increase from T1 to T2 and a lack of statistically significant
      differences from T0 to T2. Both ROIs located in the transverse suture showed a
      significant decrease in density from T0 to T1, followed by a non-significant
      increase in density from T1 to T2. CONCLUSIONS: At the end of the active phase of
      expansion a significant reduction in density along the midpalatal and transverse
      sutures was observed in all subjects. The sutural density of the midpalatal
      suture at T2 indicated reorganization of the midpalatal suture while the density
      along the transverse suture increased without reaching the pre-treatment values,
      possibly due to different morphology between midpalatal and transverse sutures.

PMID- 22996395
TI  - Relationship between the thickness of the roof of glenoid fossa, condyle
      morphology and remaining teeth in asymptomatic European patients based on cone
      beam CT data sets.
AB  - OBJECTIVES: The aim of this study was to examine the relationship between the
      roof of the glenoid fossa (RGF) thickness and condyle morphology and the
      influence of the number of remaining teeth and age. METHODS: Cone beam CT data
      sets from 77 asymptomatic European patients were analysed retrospectively in this
      study. The thinnest area of RGF was identified among the sagittal and coronal
      slices on a computer screen; distance measurement software was used to measure
      the thickness. Moreover, we applied a free digital imaging and communications in
      medicine viewer for classification of condyle head type. It was also used to
      analyse any relation between RGF thickness and the number of remaining teeth. We
      performed a correlation analysis for RGF, age and missing teeth. Finally, we
      investigated combining sagittal condyle morphological characterization with
      coronal condyle morphology in relation to the number of joints and RGF thickness.
      RESULTS: The Kruskal-Wallis test revealed no significant differences in RGF
      thickness among any of the coronal condyle head morphology groups (p > 0.05).
      There were significant differences in the thinnest part of RGF in relation to the
      sagittal plane for condyle morphological characterization, because we observed
      increased RGF thickness in joints with osteoarthritis features (p < 0.05). There
      is a non-significant correlation between the thinnest part of the RGF and the
      number of remaining teeth (p > 0.05). CONCLUSIONS: We found that the RGF
      thickness is unaffected by the coronal condyle head morphology and the number of
      remaining teeth. Osteoarthritic changes (sagittal condyle morphology) have an
      effect on RGF.

PMID- 22996396
TI  - Clinical usefulness of the Frontal Assessment Battery at bedside (FAB) for
      elderly cancer patients.
AB  - BACKGROUND: The number of elderly cancer patients has been rising in recent
      years, and decreases in cognitive function are reportedly seen in 25-50% of these
      patients. However, no validated and practical tests are available for the
      assessment of cognitive function in cancer patients. Age and the effects of
      cancer treatment have been pointed out as possible causes of these decreases in
      cognitive function; in both instances, a strong possibility of a decrease in
      frontal lobe function exists. METHODS: We administered the Frontal Assessment
      Battery at bedside (FAB), the Mini-Mental State Examination (MMSE), the Barthel
      Index, and the Instrumental Activities of Daily Living (IADL) to 54 cancer
      patients who were 65 years of age or older and assessed the clinical usefulness
      of the FAB. RESULTS: The results showed that the FAB scores were significantly
      correlated with the MMSE and IADL scores and were unaffected by the number of
      years of education. Moreover, when the subjects were divided into two groups
      according to whether their total FAB score was less than 16 points or 16 points
      or more, significant differences in the total MMSE scores and the total IADL
      scores were observed. CONCLUSIONS: Based on these findings and because the FAB
      sensitively detected decreases in cognitive function, accurately reflected the
      status of everyday life, and could be performed conveniently and in a short time,
      we concluded that the FAB may be very useful clinically as a means of evaluating
      the cognitive function of elderly cancer patients.

PMID- 22996398
TI  - The jumping-to-conclusions bias in new religious movements.
AB  - The jumping-to-conclusions bias has not been examined in a new religious movement
      (NRM) group. Twenty-seven delusion-prone NRM individuals were compared with 25
      individuals with psychotic disorders and 63 non-delusion-prone individuals on
      four probabilistic inference tasks, together with measures of psychotic symptoms
      and delusion proneness. The NRM individuals requested significantly less evidence
      when compared with the control individuals on both meaningful and nonmeaningful
      tasks. The NRM individuals requested significantly more evidence on a difficult
      meaningful task when compared with the individuals with psychotic disorders. A
      specific reasoning style but not a general reasoning style differentiates the NRM
      individuals from the individuals with psychotic disorders. These findings may be
      specific to NRM individuals and may not be generalized to other delusion-prone
      groups.

PMID- 22996399
TI  - Proapoptotic effects of the chemokine, CXCL 10 are mediated by the noncognate
      receptor TLR4 in hepatocytes.
AB  - Aberrant expression of the chemokine CXC chemokine ligand (CXCL)10 has been
      linked to the severity of hepatitis C virus (HCV)-induced liver injury, but the
      underlying molecular mechanisms remain unclear. In this study, we describe a yet
      unknown proapoptotic effect of CXCL10 in hepatocytes, which is not mediated
      through its cognate chemokine receptor, but the lipopolysaccharide receptor Toll
      like receptor 4 (TLR4). To this end, we investigated the link of CXCL10
      expression with apoptosis in HCV-infected patients and in murine liver injury
      models. Mice were treated with CXCL10 or neutralizing antibody to systematically
      analyze effects on hepatocellular apoptosis in vivo. Direct proapoptotic
      functions of CXCL10 on different liver cell types were evaluated in detail in
      vitro. The results showed that CXCL10 expression was positively correlated with
      liver cell apoptosis in humans and mice. Neutralization of CXCL10 ameliorated
      concanavalin A-induced tissue injury in vivo, which was strongly associated with
      reduced liver cell apoptosis. In vitro, CXCL10 mediated the apoptosis of
      hepatocytes involving TLR4, but not CXC chemokine receptor 3 signaling.
      Specifically, CXCL10 induced long-term protein kinase B and Jun N-terminal kinase
      activation, leading to hepatocyte apoptosis by caspase-8, caspase-3, and p21
      activated kinase 2 cleavage. Accordingly, systemic application of CXCL10 led to
      TLR4-induced liver cell apoptosis in vivo. CONCLUSION: The results identify
      CXCL10 and its noncognate receptor, TLR4, as a proapoptotic signaling cascade
      during liver injury. Antagonism of the CXCL10/TLR4 pathway might be a therapeutic
      option in liver diseases associated with increased apoptosis.

PMID- 22996400
TI  - Relationships between nitrogen transformation rates and gene abundance in a
      riparian buffer soil.
AB  - Denitrification is a critical biogeochemical process that results in the
      conversion of nitrate to volatile products, and thus is a major route of nitrogen
      loss from terrestrial environments. Riparian buffers are an important management
      tool that is widely utilized to protect water from non-point source pollution.
      However, riparian buffers vary in their nitrate removal effectiveness, and thus
      there is a need for mechanistic studies to explore nitrate dynamics in buffer
      soils. The objectives of this study were to examine the influence of specific
      types of soluble organic matter on nitrate loss and nitrous oxide production
      rates, and to elucidate the relationships between these rates and the abundances
      of functional genes in a riparian buffer soil. Continuous-flow soil column
      experiments were performed to investigate the effect of three types of soluble
      organic matter (citric acid, alginic acid, and Suwannee River dissolved organic
      carbon) on rates of nitrate loss and nitrous oxide production. We found that
      nitrate loss rates increased as citric acid concentrations increased; however,
      rates of nitrate loss were weakly affected or not affected by the addition of the
      other types of organic matter. In all experiments, rates of nitrous oxide
      production mirrored nitrate loss rates. In addition, quantitative polymerase
      chain reaction (qPCR) was utilized to quantify the number of genes known to
      encode enzymes that catalyze nitrite reduction (i.e., nirS and nirK) in soil that
      was collected at the conclusion of column experiments. Nitrate loss and nitrous
      oxide production rates trended with copy numbers of both nir and 16s rDNA genes.
      The results suggest that low-molecular mass organic species are more effective at
      promoting nitrogen transformations than large biopolymers or humic substances,
      and also help to link genetic potential to chemical reactivity.

PMID- 22996401
TI  - The Tens Rule in invasion biology: measure of a true impact or our lack of
      knowledge and understanding?
AB  - The Tens Rule, as well as the last stage described therein, i.e., the proportion
      of established species that becomes pests, is frequently perceived by the
      scientific community to indicate that introduced established species have little
      impact on communities. This belief is dangerous because it strengthens the
      perspective of the general public and decision makers that the risks of species
      introductions are largely overestimated. It is often difficult to detect the
      actual negative impact of an introduced established species. It might be less
      apparent or indirect; it might be delayed or masked by the "noise" caused by
      other anthropogenic disturbances. It is also likely that numerous ecological
      interactions are still not detected or properly understood. Therefore, the ten
      percent rule might be more of an indicator of our lack of understanding of the
      impacts that established introduced species produce than the actual ratio of such
      species that produces negative impacts. In such a state of affairs, adopting the
      precautionary principle is crucial. The scientific community must be much more
      cautious and responsible regarding the message it delivers to the general public
      and management authorities.

PMID- 22996397
TI  - Spinocerebellar ataxia type 2: clinical presentation, molecular mechanisms, and
      therapeutic perspectives.
AB  - Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant genetic disease
      characterized by cerebellar dysfunction associated with slow saccades, early
      hyporeflexia, severe tremor of postural or action type, peripheral neuropathy,
      cognitive disorders, and other multisystemic features. SCA2, one of the most
      common ataxias worldwide, is caused by the expansion of a CAG triplet repeat
      located in the N-terminal coding region of the ATXN2 gene, which results in the
      incorporation of a segment of polyglutamines in the mutant protein, being longer
      expansions associated with earlier onset and more sever disease in subsequent
      generations. In this review, we offer a detailed description of the clinical
      manifestations of SCA2 and compile the experimental evidence showing the
      participation of ataxin-2 in crucial cellular processes, including messenger RNA
      maturation and translation, and endocytosis. In addition, we discuss in the light
      of present data the potential molecular mechanisms underlying SCA2 pathogenesis.
      The mutant protein exhibits a toxic gain of function that is mainly attributed to
      the generation of neuronal inclusions of phosphorylated and/or proteolytic
      cleaved mutant ataxin-2, which might alter normal ataxin-2 function, leading to
      cell dysfunction and death of target cells. In the final part of this review, we
      discuss the perspectives of development of therapeutic strategies for SCA2. Based
      on previous experience with other polyglutamine disorders and considering the
      molecular basis of SCA2 pathogenesis, a nuclei-acid-based strategy focused on the
      specific silencing of the dominant disease allele that preserves the expression
      of the wild-type allele is highly desirable and might prevent toxic
      neurodegenerative sequelae.

PMID- 22996402
TI  - Brain-wide white matter tract integrity is associated with information processing
      speed and general intelligence.

PMID- 22996403
TI  - Blood neutrophil-to-lymphocyte ratio correlates with tumor size in patients with
      differentiated thyroid cancer.
AB  - BACKGROUND AND OBJECTIVES: Inflammation has been implicated in the initiation and
      progression of thyroid cancer. Neutrophil-to-lymphocyte ratio (NLR) is a simple
      index of systemic inflammatory response, and has been shown to be a prognostic
      indicator in some types of cancer. The aim of this study was to examine the
      relationship between NLR and clinicopathological features in patients with
      differentiated thyroid cancer. METHODS: Total white blood cell and differential
      counts of 159 patients with differentiated thyroid cancer were compared to those
      of 318 age- and sex-matched controls undergoing thyroidectomy for benign thyroid
      nodules. Clinicopathological variables, stratified by NLR tertiles, were
      analyzed. RESULTS: There was no difference in NLR between patients having benign
      and malignant thyroid nodules (P = 0.293). Cancer patients in the higher NLR
      tertile had significantly larger tumor size (P = 0.004). Higher NLR was observed
      in patients with high American Thyroid Association (ATA) risk of recurrence.
      CONCLUSIONS: High preoperative NLR was associated with increased tumor size and
      high ATA risk of recurrence in patients with differentiated thyroid cancer.

PMID- 22996405
TI  - Organic molecules as mediators and catalysts for photocatalytic and
      electrocatalytic CO2 reduction.
AB  - Reduction of CO(2) by electrochemical and photoelectrochemical methods to produce
      carbon-rich fuels is a heavily pursued research theme. Most of the current
      efforts are focused on the development of transition-metal-based catalysts. In
      this tutorial review, we present an overview of the development of organic
      molecules as mediators and catalysts for CO(2) reduction. Four classes of organic
      molecules are discussed: tetraalkylammonium salts, aromatic esters and nitriles,
      ionic liquids, and pyridinium derivatives. It is shown that reactions mediated or
      catalyzed by these organic molecules can be competitive compared to their metal
      catalyzed counterparts, both in terms of product selectivity and energy
      efficiency.

PMID- 22996404
TI  - Molecular docking and receptor-specific 3D-QSAR studies of acetylcholinesterase
      inhibitors.
AB  - The reversible inhibition of acetylcholinesterase (AChE) has become a promising
      target for the treatment of Alzheimer's disease (AD) which is mainly associated
      with low in vivo levels of acetylcholine (ACh). The availability of AChE crystal
      structures with and without a ligand triggered the effort to find a structure
      based design of acetylcholinesterase inhibitors (AChEIs) for AD. The major
      problem observed with the structure-based design was the feeble robustness of the
      scoring functions toward the correlation of docking scores with inhibitory
      potencies of known ligands. This prompted us to develop new prediction models
      using the stepwise regression analysis based on consensus of different docking
      and their scoring methods (GOLD, LigandFit, and GLIDE). In the present
      investigation, a dataset of 91 molecules belonging to 9 different structural
      classes of heterocyclic compounds with an activity range of 0.008 to 281,000 nM
      was considered for docking studies and development of AChE-specific 3D-QSAR
      models. The model (M1) developed using consensus of docking scores of scoring
      functions viz. Glide score, Gold score, Chem score, ASP score, PMF score, and
      DOCK score was found to be the best (R(2) = 0.938, Q(2) = 0.925, R(pred)(2) =
      0.919, R(2)m((overall)) = 0.936) compared to other consensus models. Docking
      studies revealed that the molecules with proper alignment in the active site
      gorge and the ability to interact with all the crucial amino acid residues, in
      particular by forming pi-pi stacking interactions with Trp84 at the catalytic
      anionic site (CAS) and Trp279 at peripheral anionic site (PAS), showed augmented
      potencies with consequent improvement in patient cognition and reduced the
      formation of senile plaques associated with AD. Further, the descriptors that
      signify the association of the ligands with the receptor as well as ADME
      properties of the ligands were also analyzed by means of the set of ligands that
      have been pre-positioned with respect to a receptor after docking analysis and
      considered as independent variables to generate a linear model (M3 and M4) using
      a stepwise multiple linear regression method to get additional insight into the
      physicochemical requirements for effective binding of ligands with AChE as well
      as for prediction of AChE inhibition. The developed AChE-specific prediction
      models (M1-M4) satisfactorily reflect the structure-activity relationship of the
      existing AChEIs and have all the potential to facilitate the process of design
      and development of new potent AChEIs.

PMID- 22996407
TI  - National Standards for Diabetes Self-Management Education and Support: updated
      and revised 2012.

PMID- 22996406
TI  - Curcumin uptake and metabolism.
AB  - Curcumin (CUR) is the major orange pigment of turmeric and believed to exert
      beneficial health effects in the gastrointestinal tract and numerous other organs
      after oral intake. However, an increasing number of animal and clinical studies
      show that the concentrations of CUR in blood plasma, urine, and peripheral
      tissues, if at all detectable, are extremely low even after large doses. The
      evidence and possible reasons for the very poor systemic bioavailablity of CUR
      after oral administration are discussed in this brief review. Major factors are
      the chemical instability of CUR at neutral and slightly alkaline pH, its
      susceptibility to autoxidation, its avid reductive and conjugative metabolism,
      and its poor permeation from the intestinal lumen to the portal blood. In view of
      the very low intestinal bioavailablity, it is difficult to attribute the putative
      effects observed in peripheral organs to CUR. Therefore, metabolites and/or
      degradation products of CUR should be taken into consideration as mediators of
      the pharmacological activity.

PMID- 22996408
TI  - Reinvention for the future of diabetes education.

PMID- 22996411
TI  - National standards for diabetes self-management education and support.

PMID- 22996412
TI  - The kinetics and character of the intermediates formed in the reaction between
      sodium nitroprusside and hydrogen sulfide need further clarification.

PMID- 22996413
TI  - 1J(CC)-edited HSQC-1,n-ADEQUATE: a new paradigm for simultaneous direct and long
      range carbon-carbon correlation.
AB  - Establishing the carbon skeleton of a molecule greatly facilitates the process of
      structure elucidation, leaving only heteroatoms to be inserted, heterocyclic
      rings to be closed, and stereochemical features to be defined. INADEQUATE, and
      more recently PANACEA, have been the only means of coming close to the goal of
      totally defining the carbon skeleton of a molecule. Unfortunately, the extremely
      low sensitivity and prodigious sample requirements of these experiments and the
      multiple receiver requirement for the latter experiment have severely restricted
      the usage of these experiments. Proton-detected ADEQUATE experiments, in
      contrast, have considerably higher sensitivity and more modest sample
      requirements. By combining experiments such as 1,1-ADEQUATE and 1,n-ADEQUATE with
      higher sensitivity experiments such as GHSQC through covariance processing,
      sample requirements can be further reduced with a commensurate improvement in the
      s/n ratio and F(1) resolution of the covariance processed spectrum. We now wish
      to report the covariance processing of an inverted (1)J(CC) 1,n-ADEQUATE
      experiment with a non-edited GHSQC spectrum to afford a spectrum that can trace
      the carbon skeleton of a molecule with the exception of correlations between
      quaternary carbons.

PMID- 22996415
TI  - [PEB treatment of testicular cancer].
AB  - The combination of cisplatin, etoposide and bleomycin (PEB) is considered to be
      the standard therapy in adjuvant situations for non-seminomas with vascular
      invasion (1-2 cycles) and for metastatic seminomas as well as non-seminomas (3-4
      cycles). In the case of contraindications to bleomycin - above all restrictive
      pulmonary diseases have to be mentioned - 4*PE can be used in place of 3*PEB. If
      the patient needs 4 cycles bleomycin can be replaced by ifosfamide. Essential
      examinations before starting therapy are general laboratory values, creatinine
      clearance and pulmonary function tests. Since the chemotherapy can suppress
      spermatogenesis temporarily or, at higher doses, for longer times, an initial at
      least hormonal examination should be performed or cryoconservation be recommended
      to the patient. Most important is the performance of the therapy cycles at
      intervals of 21 days. Delays are only justified in cases of febrile neutropenia
      or thrombocytopenia < 100 000/nL. The generally accepted lower limiting value for
      leukocytes is not per se valid in cases of testicular cancer. In the case of
      pronounced myelosuppression a growth factor can be administered prophylactically
      prior to the next cycle. A sufficient consumption of water before and after
      administration of the drugs is important, an antiemetic agent is routinely mixed
      with infusions. It is also important to provide the patient with the necessary
      medication for a possible delayed vomiting. In the follow-up of patients after
      PEB late toxicities such as the occurrence of a second malignancy must be taken
      into consideration.

PMID- 22996416
TI  - Adiposity of Korean school-age children measured by national and international
      growth charts.
AB  - The study was conducted to explore adiposity levels of Korean children using body
      mass index (BMI) and comparing how three BMI charts define adiposity. The charts
      used were the growth standard of the Korean Centers for Disease Control and
      Prevention and the growth references of the World Health Organization and the
      International Obesity Task Force. The percentage of children at different
      adiposity levels varied depending on which chart was used. These discrepancies
      arose from the different cut-offs for adiposity and the different characteristics
      of the populations that were used to develop the charts. Research is needed to
      identify which growth charts and cut-offs for children are most associated with
      health risks in later life.

PMID- 22996418
TI  - Efficient synthesis of oxygenated terphenyls and other oligomers: sequential
      arylation reactions through phenol oxidation-rearomatization.
AB  - One by one: starting from simple phenols, a diverse series of oxygenated
      terphenyl compounds can be prepared in a concise and practical manner using
      sequential arylation reactions involving phenol oxidation/rearomatization and
      quinone monoacetal intermediates. Many of the terphenyl products can be used for
      preparing well-defined oligomers and, furthermore, contain valuable functional
      groups that can be transformed for further diversification.

PMID- 22996417
TI  - Ticks of the Central African Republic.
AB  - A review is presented of the ticks of the Central African Republic (C.A.R.),
      based on unpublished data and a literature review. We consider as established in
      the C.A.R. two species of Argasidae (one species of each of the genera Carios and
      Ornithodoros) and 49 species of Ixodidae: 5 Ixodes, 11 Amblyomma, 2 Dermacentor,
      9 Haemaphysalis, 4 Hyalomma, and 18 Rhipicephalus species, 3 of which belong to
      the subgenus Boophilus. Two of these species, one Amblyomma and one Dermacentor,
      may by now have disappeared from the country together with their hosts, the black
      and white rhinoceroses. Moreover, four other species of Ixodidae have been
      recorded, but are not necessarily established in the country, and 6 species of
      Ixodidae have apparently been reported incorrectly; the data for the occurrence
      of three other species of Ixodidae are uncertain. Rhipicephalus species in the
      C.A.R. present the greatest difficulties in identification, on the one hand
      because of uncertainties in taxonomy, particularly in the capensis group, on the
      other hand because of individual variability, which means that individual
      specimens cannot always be reliably identified to species. Examining the
      dissected and cleared gonopore structure of females helps, but is very time
      consuming where large numbers are involved. Some of the species of the genus
      Haemaphysalis are also difficult to identify with certainty. There are only a few
      species of Hyalomma in the country. We revised also some old records of ticks in
      C.A.R., which we consider as unreliable and should be disregarded because of
      subsequent changes in taxonomy and nomenclature, unless the material is still
      available for examination.

PMID- 22996419
TI  - Time-resolved MR venography of the pulmonary veins precatheter-based ablation for
      atrial fibrillation.
AB  - PURPOSE: To evaluate time-resolved magnetic resonance angiography (TR-MRA) of the
      pulmonary venous circulation using the time-resolved angiography with interleaved
      stochastic trajectories (TWIST) method and compare it with the more commonly used
      conventional contrast-enhanced magnetic resonance angiography (CE-MRA) approach
      in atrial fibrillation patients referred for preablation pulmonary vein mapping.
      MATERIALS AND METHODS: This study was approved by the Institutional Review Board.
      Twenty-six patients (15 males; age 59.6 +/- 12.7 years) referred for preablation
      pulmonary vein mapping underwent both conventional CE-MRA and TR-MRA with TWIST.
      Imaging was performed on a 1.5 T (Magnetom Avanto, Siemens Healthcare, Erlangen,
      Germany) MRI scanner. Source partition and maximum intensity projection (MIP)
      images were evaluated retrospectively. For quantitative analysis, pulmonary vein
      ostium orthogonal dimensions were measured using double oblique multiplanar
      reformatting. The results were analyzed using paired t-tests, Lin's concordance
      correlation coefficient, and Bland-Altman plots. For qualitative analysis, both
      source partition images and MIP images were assessed by two observers (A.P. and
      M.G.). The presence of common ostiums or accessory veins was recorded and
      analyzed using unweighted Cohen's kappa. Pulmonary vein conspicuity was scored on
      a scale of 1-4 (1 = poor, 2 = fair, 3 = good, 4 = excellent) and analyzed using
      paired t-tests, intraclass correlation coefficients, and quadratic weighted kappa
      statistics. RESULTS: Orthogonal venous diameters were comparable for both TR-MRA
      and conventional CE-MRA (1.34 +/- 0.37 vs. 1.38 cm +/- 0.36, respectively).
      Results of paired t-tests, Lin's concordance correlation coefficient, and Bland
      Altman analysis revealed relatively close comparison between methods. The
      magnitude of the mean difference for any of the statistical comparisons did not
      exceed 0.10 cm. The visualization of variant pulmonary vein anatomy was very
      similar for both techniques. Agreement between techniques was determined to be
      "good" to "very good" (kappa = 0.78-0.85). Conspicuity scores for each pulmonary
      vein were also very close. Paired t-tests, intraclass correlation coefficients,
      and quadratic weighted kappa statistics all revealed strong agreement between
      methods. CONCLUSION: TR-MRA using TWIST produces comparable anatomic images and
      pulmonary venous dimensions to the more widely used CE-MRA technique.
      Additionally, the TWIST technique improves arterio-venous separation, does not
      need exact bolus timing, requires less gadolinium, and gives additional
      information on vein perfusion.

PMID- 22996420
TI  - The neutrophil elastase mutant affects viability and differentiation of the human
      monocytic THP-1 cell.
AB  - Deficiency in neutrophils (neutropenia) caused by mutations in neutrophil
      elastase (NE, ELA2) has been extensively investigated. Monocytes and neutrophils
      are derived from a common myeloid progenitor; therefore, ELA2 mutations can also
      influence monocyte development. These effects have not been well described. In
      this study, we used the human monocytic THP-1, to carry the human wild-type and
      G185R mutant ELA2 gene. Growth, death, differentiation and BiP expression were
      evaluated in the two stable cell lines and in the wild-type THP-1 cells.
      Exogenous wild-type ELA2 markedly increased THP-1 differentiation, whereas G185R
      ELA2 was incompetent to promote THP-1 differentiation in response to all-trans
      retinoic acid (ATRA). Indeed, during differentiation induced by ATRA, G185R cell
      line showed significant cell death. Also, up-regulated BiP expression accompanied
      cell death in the G185R cells, suggesting that the overexpression of G185R
      elastase increases apoptosis through an unfolded protein response. The G185R
      cells treated with lithium chloride (LiCl; a Wnt signalling activator) displayed
      higher BiP expression but similar cell viability compared with THP1 and
      HNEwt/THP1 cells treated with LiCl. This suggested that Wnt signalling might
      increase cellular tolerance to endoplasmic reticulum stress, enabling mutant
      monocyte survival.

PMID- 22996421
TI  - [Mistletoe extract for treatment of urological tumors].
AB  - In Germany misteltoe extract is one of the most commonly used complementary
      therapeutic strategies in oncology. There are anthroposophical as well as
      phytotherapeutic concepts to explain the potential mechanism of action; however,
      the oncological and uro-oncological literature lacks definitive proof to support
      recommendations on which is the most effective drug, the optimal dose, a clear
      indication or its efficacy. Weighting the current data, potential side effects
      and contraindications, the application of mistletoe extract in daily uro
      oncological practice requires careful consideration of the indications in the
      context of a detailed patient informed consent and request for this unique
      therapeutic modality.

PMID- 22996422
TI  - [Laparoendoscopic single-site surgery in urology using reusable systems].
AB  - PURPOSE: Many disposable platforms have been available for laparoendoscopic
      single-site surgery (LESS) for a long time. Besides technical challenges cost
      remains the limiting factor for the widespread use of LESS. We present our
      experiences with the first completely reusable LESS platform. METHODS: We
      performed LESS procedures in 52 patients, including nephrectomy (n=18),
      adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation
      (4), pelvic lymphadenectomy (15) and lymphocele ablation (6). All procedures were
      carried out using a novel reusable single-port device (X-ConeR, Karl-Storz) with
      a simplified combination of standard and preformed instruments. Perioperative and
      demographic data including a visual analogue pain scale (VAS) were obtained.
      Complications were recorded using the Clavien classification. RESULTS: The mean
      age of the patients was 50.04 years. Conversion to standard laparoscopy was
      necessary in 3 cases and the additional use of a 3 mm needle instrument in 6
      cases. There were no open conversions. Intraoperative and postoperative
      complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operating
      time was 110, 90, and 89 min and hospital stay was 4.9, 3.1 and 3.6 days for
      nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. The mean VAS
      was 2.13, 1.07 and 1.5 while blood loss was 81.3 ml, 25.67 ml and 17.5 ml,
      respectively. CONCLUSIONS: The LESS technique with a completely reusable platform
      is applicable to various indications in urology yielding favorable functional and
      cosmetic results. This novel simplified combination of instruments facilitates
      handling and shortens the learning curve. Reusable materials may help to reduce
      cost leading to a wider acceptance of LESS.

PMID- 22996423
TI  - Cost-effectiveness, cancer burden and financial crisis: a perfect storm.

PMID- 22996424
TI  - Hepatopulmonary syndrome: favorable outcomes in the MELD exception era.
AB  - Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a
      consequence of advanced liver disease, characterized by hypoxemia due to
      intrapulmonary vascular dilatations. HPS independently increases mortality,
      regardless of the cause or severity of liver disease. Liver transplantation (LT)
      improves survival in HPS. We present the largest consecutive series of HPS
      patients specifically addressing long-term survival relative to the degree of
      hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at
      the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier
      methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5,
      and 10 years) did not differ between groups based on baseline partial pressure of
      arterial oxygen (PaO2 ) obtained at the time of HPS diagnosis. Improvements in
      overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted
      after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with
      those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively)
      did not reach statistical significance (5-year P = 0.09). Model for Endstage
      Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since
      January 1 2002 with post-LT survival of 19/21 patients and one wait-list death.
      CONCLUSION: Long-term outcome after LT in HPS is favorable, with a trend towards
      improved survival in the MELD exception era since 2002 as compared to earlier HPS
      transplants. Survival after LT was not associated with PaO2 levels at the time of
      HPS diagnosis. (HEPATOLOGY 2012).

PMID- 22996426
TI  - Transformational change: moving toward enterprise risk management through the
      Power of OneTM.
AB  - My oldest daughter, Julia, graduated from high school in June of this year. She
      leaves for college in the fall. It's not easy letting go; change is hard.
      Transformational change is harder still. Fortunately, she is being launched into
      the world with some good principles to help her focus: Be kind to your neighbor.
      Make the world a better place.

PMID- 22996425
TI  - Selective use of preoperative chemoradiotherapy for T3 rectal cancer can be
      justified: analysis of local recurrence.
AB  - BACKGROUND: Preoperative chemoradiotherapy (CXRT) is performed to reduce local
      recurrence and improve the rate of radical resection for rectal cancer.
      Currently, it is recommended for all suspected T3 rectal cancers. However, the
      survival benefit of this procedure is controversial, and complications of RT are
      often overlooked. The present study was designed to assess the validity of our
      institutional policies regarding selective use of preoperative CXRT for T3 rectal
      cancer. METHODS: From September 2006 to May 2010, we retrospectively analyzed
      data for patients with pathologic T3 rectal cancer, especially those with follow
      up for more than 18 months. Patients who underwent RT pre-/postoperatively were
      excluded. Patients who fulfilled these criteria but did not undergo RT or had
      incurable distant metastasis were also excluded. RESULTS: Of the 319 patients who
      underwent surgery for rectal cancer, 183 were diagnosed with T3 cancer. After
      excluding 58 patients, the final sample included 125 subjects with a mean follow
      up of 26.0 months. In all, 94 patients had a follow-up of more than 18 months.
      Four patients had local recurrences, and the cumulative local recurrence rate was
      3.4 % at 18 months and 5.6 % after 2 years. All four had low rectal cancer (mean
      distance 4.5 +/- 1.9 cm). Three were diagnosed as N0 and one as N1. The mean
      disease-free period was 15.0 months. The distance between the tumor and the anal
      verge was the only significant risk factor for local recurrence. CONCLUSIONS: In
      this study, the oncologic outcome for T3 rectal cancer without preoperative CXRT
      was acceptable in terms of local recurrence. Selective use of preoperative CXRT
      for T3 rectal cancer needs to be further evaluated prospectively.

PMID- 22996427
TI  - Our journey to zero: reducing serious safety events by over 70% through high
      reliability techniques and workforce engagement.
AB  - The techniques and best practices used to achieve a successful safety culture
      transformation and drive down the incidence of serious safety events are
      described. The Safety Transformation Initiative at Children's National resulted
      in national and local recognition, a financial savings of an imputed $35 million,
      and a greater than 70% decrease in the serious safety event rate over a 3-year
      period (July 1, 2008-June 30, 2011). The results were achieved during a time of
      significant financial constraints and with limited resources. A blueprint
      detailing specifics of the implementation is presented to assist others in
      achieving similar results. Our safety transformation was initiated in our fiscal
      year 2009 as part of a 3-year corporate goal. The work is continuing and we
      aspire to virtually eliminate serious safety events by 2016.

PMID- 22996428
TI  - Getting to zero: evidence-based healthcare risk management is key.
AB  - In this article we call for a new approach to patient safety improvement, one
      based on the emerging field of evidence-based healthcare risk management (EBHRM).
      We explore EBHRM in the broader context of the evidence-based healthcare
      movement, assess the benefits and challenges that might arise in adopting an
      evidence-based approach, and make recommendations for meeting those challenges
      and realizing the benefits of a more scientific approach.

PMID- 22996429
TI  - Professional collaboration to achieve FASHRM and DFASHRM recognition.
AB  - Members of the American Society for Healthcare Risk Management (ASHRM) are
      undeniably talented. They also share a spirit of volunteerism. Two ASHRM
      committees are fostering further member collaboration to provide individual
      growth, enhance educational offerings for members, and strengthen the
      organization's journal. Though 26% of ASHRM members have attained the CPHRM
      credential, only 2.5% of ASHRM members have attained a fellow designation.
      Primary barriers to attaining a fellow designation are the requirements for
      continuing education and contributions to the risk management field. The
      organization's Journal Editorial Review Board, in concert with its Annual
      Conference & Exhibition Committee, encourages members to explore opportunities to
      write for the Journal, speak at the annual conference, and attain one of the
      organization's professional designations. In addition, the Barton Certificate
      Program in Healthcare Risk Management promotes professional development with
      sessions taught on this topic for new and experienced risk managers.

PMID- 22996430
TI  - Missouri's Just Culture collaborative.
AB  - Under the leadership of the Missouri Center for Patient Safety, Missouri set the
      stage for healthcare providers and regulators to work together to improve patient
      safety by moving towards a Just Culture. By bringing together 67 healthcare
      providers, regulators and others with a goal to improve the patient safety
      culture, the collaborative led to an improved understanding of the key principles
      of Just Culture, its implementation and barriers to implementation, as well as
      how regulators could support providers in their efforts to improve the safety
      culture.

PMID- 22996431
TI  - An enterprise look at mHealth.
AB  - The theme of this year's annual American Society for Healthcare Risk Management
      conference is Getting to ZeroTM: the Power of OneTM. The widespread use of
      mHealth exemplifies the power of one. The power of one user to apply technology
      to change the way healthcare is delivered at the bedside, in the provider's
      office, and in the patient's home. The power of one organization to provide
      technology that ensures provider access to clinical information to improve
      decision making, facilitate access to clinical information, and provide new ways
      to partner with patients - wherever they may be. This article provides an
      overview of the current status of mHealth and describes risk management
      strategies appropriate for organizations of all sizes and complexities.

PMID- 22996433
TI  - Prognostic implications for high expression of oncogenic microRNAs in advanced
      gastric carcinoma.
AB  - BACKGROUND: Aberrant expressions of specific microRNAs are recently known in many
      malignancies, including gastric carcinoma. The prognostic implication of
      oncogenic microRNA dysregulation was investigated in advanced gastric carcinomas
      undergoing radical resection and adjuvant systemic chemotherapy, and observed on
      long-term follow-up. METHODS: The expression levels of miR-20a, miR-21, miR-25,
      miR-93, miR-103, miR-106a, miR-106b, miR-130b, miR-155, miR-221, and miR-222 were
      analyzed in formalin-fixed paraffin-embedded (FFPE) cancer tissues of 91
      patients, using reverse transcription real-time PCR. RESULTS: The high expression
      of miR-20a, miR-25, miR-93, miR-103, miR-106a, miR-106b, miR-130 was associated
      with lymph node metastasis (P < 0.05), and high expression of miR-155 was related
      to tumor penetration through serosa and lymph node metastasis (P < 0.05). Cases
      with high expression of miR-222 (P = 0.014) showed reduced 5-year survival rates.
      The high expression of miR-222 and miR-221 showed correlation with shorter
      metastasis-free survival (P = 0.039 and 0.033, respectively), and miR-222 high
      expression was related to reduced overall survival (P = 0.012). CONCLUSIONS: The
      high expression of miR-20a, miR-25, miR-93, miR-103, miR-106a, miR-106b, miR-130,
      miR-155, miR-221, and miR-222 in AGC tissues may be a high risk factor associated
      with tumor penetration through serosa, lymph node metastasis, distant metastasis,
      and poor long-term survival in patients undergoing radical resection and adjuvant
      systemic chemotherapy.

PMID- 22996434
TI  - Photoactivated linkage isomerism in single crystals of nickel, palladium and
      platinum di-nitro complexes--a photocrystallographic investigation.
AB  - Low temperature, single crystal photocrystallographic studies have been carried
      out on four square planar Group 10 complexes [Ni(PEt(3))(2)(NO(2))(2)] 1,
      [Pd(PPh(3))(2)(NO(2))(2)] 2, [Pd(AsPh(3))(2)(NO(2))(2)] 3 and
      [Pt(PPh(3))(2)(NO(2))(2)] 4, in which the two nitro groups adopt the trans
      configuration. Irradiation with UV light, at 100 K, of single crystals of
      complexes 1-3 photoisomerise from the eta(1)-NO(2) nitro form to the eta(1)-ONO
      nitrito form occurred. Complex 1 underwent 25% conversion to the nitrito form
      before crystal decomposition occurred. 2 and 3 underwent 46% and 39% conversion,
      respectively, to the nitrito form when a photostationary state was reached. While
      under the same experimental conditions 4 showed no isomerisation. The
      photocrystallographic results can be correlated with the results of DFT
      calculations and with the observed trends in the solution UV/visible absorption
      spectroscopy obtained for these complexes. The results suggest that while steric
      factors in the isomerization processes are important there may also be a kinetic
      effect relating to the lability of the metal involved.

PMID- 22996435
TI  - The missing links: understanding the role of motivations and power differentials
      in the sexual behaviors of young gay and bisexual males.

PMID- 22996436
TI  - Circumventing parental choice and the evolution of rape.

PMID- 22996437
TI  - Comment on "Reexamining individual differences in women's rape avoidance" by
      Snyder and Fessler (2012).

PMID- 22996438
TI  - In vitro evaluation of the fermentation properties and potential prebiotic
      activity of caprine cheese whey oligosaccharides in batch culture systems.
AB  - The prebiotic effect of oligosaccharides recovered and purified from caprine
      whey, was evaluated by in vitro fermentation under anaerobic conditions using
      batch cultures at 37 degrees C with human faeces. Effects on key gut bacterial
      groups were monitored over 24 h by fluorescence in situ hybridization (FISH),
      which was used to determine a quantitative prebiotic index score. Production of
      short-chain fatty acids (SCFAs) as fermentation end products was analyzed by high
      performance liquid chromatography (HPLC). Growth of Bifidobacterium spp was
      significantly higher (P >= 0.05) with the purified oligosaccharides compared to
      the negative control. Lactic and propionic acids were the main SCFAs produced.
      Antimicrobial activity of the oligosaccharides was also tested, revealing no
      inhibition though a decrease in Staphylococcus aureus and Escherichia coli
      growth. These findings indicate that naturally extracted oligosaccharides from
      caprine whey could be used as new and valuable source of prebiotics.

PMID- 22996439
TI  - Successful perioperative management of a patient with primary systemic carnitine
      deficiency: a case report.

PMID- 22996440
TI  - Intrinsic expression of transcortin in neural cells of the mouse brain: a
      histochemical and molecular study.
AB  - Corticosteroid binding globulin (CBG, transcortin) has been shown to be expressed
      in the brain of rat and human species. In this study, we examined the CBG brain
      expression and cDNA structure in mice, comparing wild-type (Cbg(+/+)) and Cbg
      knockout mice (Cbg(-/-), obtained by genetic disruption of the SerpinA6 alias Cbg
      gene). We used double immunofluorescence labeling with specific neuronal and
      glial markers to analyze the cellular localization of CBG in various regions of
      the mouse brain. In wild-type (Cbg(+/+)) mice, we found CBG immunoreactivity in
      neuronal perikarya of the magnocellular hypothalamic nuclei, amygdala,
      hippocampus, cerebral cortex, cerebellum and pituitary. A portion of glial cells
      (astrocytes, oligodendrocytes) contained CBG immunoreactivity, including some of
      the ependymal cells and choroid plexus cells. No CBG immunoreactivity was
      detected in Cbg(-/-) brain tissues. Using RT-PCR, we showed that the full-length
      Cbg mRNA is present in those regions, indicating an intrinsic expression of the
      steroid-binding globulin. Furthermore, sequencing analysis showed that Cbg cDNA
      obtained from the mouse hypothalamus was homologous to Cbg cDNA obtained from the
      liver. Finally, we have evaluated the relative levels of CBG expression in
      various brain regions and in the liver by quantitative PCR. We found that brain
      levels of Cbg mRNA are low compared with the liver but significantly higher than
      in CBG-deficient mice. Although derived from the same gene as liver CBG, brain
      CBG protein may play a specific or complementary role that requires the
      production and analysis of brain-specific Cbg knockout models.

PMID- 22996442
TI  - Apoptosis of Ascogregarina taiwanensis (Apicomplexa: Lecudinidae), which failed
      to migrate within its natural host.
AB  - Sexual reproduction of Ascogregarina taiwanensis (Apicomplexa: Lecudinidae), a
      parasite specific to the mosquito Aedes albopictus, in Malpighian tubules is
      initiated by the entry of the trophotozoites developed in the midgut shortly
      after pupation (usually <5 h). However, only a low proportion of trophozoites are
      able to migrate; others end up dying. In this study, we demonstrated that those
      trophozoites that failed to migrate eventually died of apoptosis. Morphological
      changes such as shrinkage, chromatin aggregations and formation of blunt ridges
      on the surface were seen in moribund trophozoites. In addition, DNA fragmentation
      of trophozoites isolated from the midgut of pupae was demonstrated by the
      presence of DNA ladders, Annexin V staining and TUNEL assays. Detection of
      caspase-like activity suggests that apoptosis of those trophozoites may have
      occurred through a mechanism of an intrinsic or mitochondrial-mediated pathway.
      Although apoptosis has been observed in various protozoan species, it is not
      clear how apoptosis in single-celled organisms might result from evolution by
      natural selection. However, we speculate that apoptosis may regulate the parasite
      load of A. taiwanensis within its natural mosquito host, leading to an optimized
      state of the survival rate for both parasite and host.

PMID- 22996443
TI  - Feature-positive and feature-negative learning in honey bees.
AB  - Honey bees (Apis mellifera anatolica) were subjected to sequential trials where
      they were given the choice between a feature-positive and a feature-negative
      feeding plate. The 'feature' being manipulated is the presence of a single blue
      circle among three circles marking the location of a small sucrose reward. That
      is, a 'feature-negative' target had three white circles, while a 'feature
      positive' target had two white circles and one blue one. Two experiments were
      performed. In both experiments, each bee was tested under two different reward
      scenarios (treatments). In the first experiment, during the feature-positive
      treatment bees received 4 MUl of 2 mol l(-1) sucrose when choosing the feature
      positive plate, but received 4 MUl of saturated NaCl solution (saltwater) when
      choosing the feature-negative plate. During the feature-negative treatment, bees
      were rewarded when visiting the feature-negative plate, while visitation to the
      feature-positive plate only offered bees the saltwater. The second experiment was
      a repeat of the first except that pure water was offered instead of saltwater in
      the non-rewarding feeding plate. As an experimental control, a set of bees was
      offered sequential trials where both the feature-positive and feature-negative
      plates offered the sucrose reward. Bee feeding plate choice differed between the
      feature-positive and feature-negative treatments in both experiments. Bees
      favored the feeding plate type with the sucrose reward in each treatment, and
      never consumed the saltwater or pure water when encountered in either treatment.
      Further, behavior of bees during both the feature-positive and feature-negative
      treatments differed from that of control bees. However, neither feature-positive
      nor feature-negative learning reached high levels of success. Further, a feature
      positive effect was seen when pure water was offered; bees learned to solve the
      feature-positive problem more rapidly. When we tested bees using simply the
      choice of blue versus white targets, where one color held the sucrose reward and
      the other the saltwater, a bee's fidelity to the color offering the sucrose
      reward quickly reached very high levels.

PMID- 22996441
TI  - Associative learning in the dengue vector mosquito, Aedes aegypti: avoidance of a
      previously attractive odor or surface color that is paired with an aversive
      stimulus.
AB  - Associative learning has been shown in a variety of insects, including the
      mosquitoes Culex quinquefasciatus and Anopheles gambiae. This study demonstrates
      associative learning for the first time in Aedes aegypti, an important vector of
      dengue, yellow fever and chikungunya viruses. This species prefers to rest on
      dark surfaces and is attracted to the odor of 1-octen-3-ol. After training in
      which a dark surface alone or a dark surface with odor was paired with electric
      shock, mosquitoes avoided the previously attractive area. The association was
      stronger when odor was included in training, was retained for at least 60 min but
      not for 24 h, and was equal for males and females. These results demonstrate the
      utility of a bulk-training paradigm for mosquitoes similar to that used with
      Drosophila melanogaster.

PMID- 22996444
TI  - Protein-induced mass increase of the gastrointestinal tract of locusts improves
      net nutrient uptake via larger meals rather than more efficient nutrient
      absorption.
AB  - Increasing the tissue biomass and/or volume of the gastrointestinal tract (GIT)
      is commonly seen when animals feed on poor-quality diets. This increase can
      simply permit larger meal sizes, but may also rebalance nutritionally imbalanced
      ingesta by allowing selective absorption of limiting nutrients. In an insect
      herbivore, the migratory locust, a synthetic diet with a high ratio of protein to
      carbohydrate was found to induce mass enhancement of the GIT. When normalised for
      sex and overall body size, increases to the mass of the foregut and midgut caeca
      resulted in higher absorption (20-30%) of both protein and carbohydrate when
      subsequently feeding on three chemically and structurally different grasses.
      Greater net absorption of macronutrients occurred because these locusts ate
      larger meals that transited at the same time and with the same digestive
      efficiency as locusts in which the GIT was not enlarged. Thus, plasticity of the
      GIT did not improve nutritional homeostasis, but increased the rate of nutrient
      uptake.

PMID- 22996445
TI  - Walking on smooth and rough ground: activity and timing of the claw retractor
      muscle in the beetle Pachnoda marginata peregrina (Coleoptera, Scarabaeidae).
AB  - The activity pattern of the claw retractor muscle of Pachnoda marginata peregrina
      beetles was examined in this study. We found this muscle to be located in the
      tibia, without a femoral part, as is the case in other insects. Electromyograms
      of the muscle revealed a rather similar activity pattern during beetle locomotion
      on rough and smooth substrates. We recorded units with small and large amplitude,
      with the smaller unit being active during almost the entire stance phase, and the
      larger unit active roughly in the first half of stance. Small but significant
      differences were found in the precise onset and end of activity. Both small and
      large units began their activity earlier on the rough surface. Although there was
      no difference at the end of activity in the small unit between surfaces, the
      large unit ended its activity significantly earlier on the rough substrate. The
      spike frequencies on both surfaces were also significantly different for small
      and large units. The small unit showed a higher spike frequency on the smooth
      surface, while the large unit had a higher spike frequency on the rough surface.
      From our experiments, we conclude that the muscle is controlled by the same basic
      activity pattern on different surfaces, with some adjustments that are due to
      sensory feedback. The adjustments cause differences in onset and end of activity,
      as well as in spike frequency of the involved muscle units.

PMID- 22996446
TI  - An effective method for terrestrial arthropod euthanasia.
AB  - As scientific understanding of invertebrate life increases, so does the concern
      for how to end that life in an effective way that minimises (potential) suffering
      and is also safe for those carrying out the procedure. There is increasing debate
      on the most appropriate euthanasia methods for invertebrates as their use in
      experimental research and zoological institutions grows. Their popularity as pet
      species has also led to an increase in the need for greater veterinary
      understanding. Through the use of a local injection of potassium chloride (KCl)
      initially developed for use in American lobsters, this paper describes a safe and
      effective method for euthanasia in terrestrial invertebrates. Initial work
      focused on empirically determining the dose for cockroaches, which was then
      extrapolated to other arthropod species. For this method of euthanasia, we
      propose the term 'targeted hyperkalosis' to describe death through terminal
      depolarisation of the thoracic ganglia as a result of high potassium
      concentration.

PMID- 22996447
TI  - Tracking bed bugs (Cimex lectularius): a study of the effect of physiological and
      extrinsic factors on the response to bed bug-derived volatiles.
AB  - The common bed bug, Cimex lectularius, feeds on the blood of mammal and bird
      hosts, and is a pest of global importance. Semiochemicals are chemicals involved
      in animal communication that may affect behaviour and/or physiology. Attractive
      semiochemicals that play a role in mediating bed bug behaviour could be exploited
      for the development of a highly effective novel monitoring device. Tracking
      software was used to record the response of bed bugs to volatiles from paper
      previously exposed to conspecific bugs in a still-air olfactometer illuminated by
      infrared lights, through a variety of activity variables. The effect of time of
      day as an extrinsic factor, and sex, stage, mating status and nutritional status
      as physiological factors on the response of bed bugs to the volatiles was
      examined. Bed bugs of both sexes and all stages responded to the volatiles from
      bed bug-exposed papers, showing significant attraction and orientation towards
      the volatile source whether they were starved or engorged. Confirmation that the
      physiological factors examined do not affect the response of bed bugs to the
      volatiles from bed bug-exposed papers provides evidence that these bed bug
      derived volatiles contain aggregation cues, as semiochemicals that promote
      aggregation should by definition be detected by both sexes and all life stages. A
      device baited with such semiochemicals could play a major role in limiting the
      impact of the current bed bug resurgence by enabling timely detection of
      infestations, along with quantitative evaluation of control and effective
      surveillance of the geographical distribution of the pest species.

PMID- 22996448
TI  - Rapid decline of cold tolerance at young age is associated with expression of
      stress genes in Drosophila melanogaster.
AB  - Many endogenous factors influence thermal tolerance of insects. Among these, age
      contributes an important source of variation. Heat tolerance is typically high in
      newly eclosed insects, before declining dramatically. It is not known whether
      this phenomenon relates to cold tolerance also. In addition, the underlying
      mechanisms of this variation are unresolved. In this study, we tested whether
      cold tolerance declines in Drosophila melanogaster females aged from 0 to 5 days.
      We also assessed whether expression (basal and induced) of eight stress genes
      (hsp22, hsp23, hsp40, hsp68, hsp70Aa, hsp83, Starvin and Frost) varied post
      eclosion in correspondence with changes found in cold tolerance. We report that
      cold tolerance was very high at eclosion and then it rapidly declined in young
      flies. hsp23 and hsp68 showed a dramatic age-related variation of basal
      expression that was associated with cold tolerance proxies. Significant age
      related plasticity of cold-induced expression was also found for hsp22, hsp23,
      hsp68, hsp70Aa, Frost and Starvin. Induced expression of hsp22 and hsp70Aa was
      high in newly enclosed phenotypes before declining dramatically, whilst opposite
      age-related patterns were found for hsp23, hsp68, Starvin and Frost. This study
      shows a marked within-stage variation in cold tolerance. The involvement of the
      stress genes in setting basal thermal tolerance is discussed.

PMID- 22996449
TI  - Ventilation rates and activity levels of juvenile jumbo squid under metabolic
      suppression in the oxygen minimum zone.
AB  - The Humboldt (jumbo) squid, Dosidicus gigas, is a part-time resident of the
      permanent oxygen minimum zone (OMZ) in the Eastern Tropical Pacific and, thereby,
      it encounters oxygen levels below its critical oxygen partial pressure. To better
      understand the ventilatory mechanisms that accompany the process of metabolic
      suppression in these top oceanic predators, we exposed juvenile D. gigas to the
      oxygen levels found in the OMZ (1% O(2), 1 kPa, 10  degrees C) and measured
      metabolic rate, activity cycling patterns, swimming mode, escape jet (burst)
      frequency, mantle contraction frequency and strength, stroke volume and oxygen
      extraction efficiency. In normoxia, metabolic rate varied between 14 and 29 MUmol
      O(2) g(-1) wet mass h(-1), depending on the level of activity. The mantle
      contraction frequency and strength were linearly correlated and increased
      significantly with activity level. Additionally, an increase in stroke volume and
      ventilatory volume per minute was observed, followed by a mantle hyperinflation
      process during high activity periods. Squid metabolic rate dropped more than 75%
      during exposure to hypoxia. Maximum metabolic rate was not achieved under such
      conditions and the metabolic scope was significantly decreased. Hypoxia changed
      the relationship between mantle contraction strength and frequency from linear to
      polynomial with increasing activity, indicating that, under hypoxic conditions,
      the jumbo squid primarily increases the strength of mantle contraction and does
      not regulate its frequency. Under hypoxia, jumbo squid also showed a larger
      inflation period (reduced contraction frequency) and decreased relaxed mantle
      diameter (shortened diffusion pathway), which optimize oxygen extraction
      efficiency (up to 82%/34%, without/with consideration of 60% potential skin
      respiration). Additionally, they breathe 'deeply', with more powerful
      contractions and enhanced stroke volume. This deep-breathing behavior allows them
      to display a stable ventilatory volume per minute, and explains the maintenance
      of the squid's cycling activity under such O(2) conditions. During hypoxia, the
      respiratory cycles were shorter in length but increased in frequency. This was
      accompanied by an increase in the number of escape jets during active periods and
      a faster switch between swimming modes. In late hypoxia (onset ~170 +/- 10 min),
      all the ventilatory processes were significantly reduced and followed by a
      lethargic state, a behavior that seems closely associated with the process of
      metabolic suppression and enables the squid to extend its residence time in the
      OMZ.

PMID- 22996450
TI  - Analysis of the transitional flow field over a fixed hummingbird wing.
AB  - We analyzed the flow fields characterized by chord-based Reynolds numbers of 5000
      to 15,000 over a stationary model of a hummingbird (Calypte anna) wing. Utilizing
      two experimental techniques, constant-temperature anemometry and stereo particle
      image velocimetry, the high-fidelity results depict a laminar-to-turbulent
      transition process that develops over the wing. At both zero and non-zero angles
      of attack the spectrum of the velocity signals is wide. At non-zero angles of
      attack the flow separates from the wing surface and a shear layer forms. As a
      result, unsteady flow disturbances amplify at a chord-based Reynolds numbers as
      low as 5000. Nevertheless, only at a Reynolds number of 15,000 is the flow
      disturbance growth rate sufficient to bring enough momentum from the outer region
      of the boundary layer to reattach the flow to the wing surface. For a Reynolds
      number of 5000, a comparison between the observed growth rates and a theoretical
      approximation concludes that flow disturbances of a Strouhal number of unity (and
      above) are no longer two-dimensional. In view of these conclusions, this study
      could serve as the first step towards a better understanding of the flow
      mechanisms over steady revolving and periodically flapping wings at this Reynolds
      number regime.

PMID- 22996452
TI  - Back to the future?

PMID- 22996453
TI  - Banana root fracture.

PMID- 22996451
TI  - Pemphigus autoantibodies generated through somatic mutations target the
      desmoglein-3 cis-interface.
AB  - Pemphigus vulgaris (PV) is an autoimmune blistering disease of skin and mucous
      membranes caused by autoantibodies to the desmoglein (DSG) family proteins DSG3
      and DSG1, leading to loss of keratinocyte cell adhesion. To learn more about
      pathogenic PV autoantibodies, we isolated 15 IgG antibodies specific for DSG3
      from 2 PV patients. Three antibodies disrupted keratinocyte monolayers in vitro,
      and 2 were pathogenic in a passive transfer model in neonatal mice. The epitopes
      recognized by the pathogenic antibodies were mapped to the DSG3 extracellular 1
      (EC1) and EC2 subdomains, regions involved in cis-adhesive interactions. Using a
      site-specific serological assay, we found that the cis-adhesive interface on EC1
      recognized by the pathogenic antibody PVA224 is the primary target of the
      autoantibodies present in the serum of PV patients. The autoantibodies isolated
      used different heavy- and light-chain variable region genes and carried high
      levels of somatic mutations in complementary-determining regions, consistent with
      antigenic selection. Remarkably, binding to DSG3 was lost when somatic mutations
      were reverted to the germline sequence. These findings identify the cis-adhesive
      interface of DSG3 as the immunodominant region targeted by pathogenic antibodies
      in PV and indicate that autoreactivity relies on somatic mutations generated in
      the response to an antigen unrelated to DSG3.

PMID- 22996454
TI  - Step in the right direction.

PMID- 22996455
TI  - Smokeless evidence.

PMID- 22996456
TI  - Barred from consideration.

PMID- 22996457
TI  - Thyroid protection.

PMID- 22996458
TI  - Shameful situation.

PMID- 22996460
TI  - More practicable.

PMID- 22996472
TI  - The management of dental anxiety: time for a sense of proportion?
AB  - Dental anxiety and fear are common and potentially problematic, both for the
      patient and for the dental team in managing such patients. Furthermore, dental
      fear still presents a major barrier to the uptake of dental treatment. This
      article will take as its premise an assumption that anxiety manifests at
      different levels and that consequently management of dental anxiety involves both
      assessment and proportionate intervention. Methods for undertaking both
      assessment and management are outlined.

PMID- 22996473
TI  - Oral diagnosis and treatment planning: part 6. Preventive and treatment planning
      for periodontal disease.
AB  - A high level of sustained personal plaque control is fundamental for successful
      treatment outcomes in patients with active periodontal disease and, hence, oral
      hygiene instructions are the cornerstone of periodontal treatment planning. Other
      risk factors for periodontal disease also should be identified and modified where
      possible. Many restorative dental treatments in particular require the
      establishment of healthy periodontal tissues for their clinical success. Failure
      by patients to control dental plaque because of inappropriate designs and
      materials for restorations and prostheses will result in the long-term failure of
      the restorations and the loss of supporting tissues. Periodontal treatment
      planning considerations are also very relevant to endodontic, orthodontic and
      osseointegrated dental implant conditions and proposed therapies.

PMID- 22996478
TI  - Summary of: investigation of inhalational conscious sedation as a tool for
      reducing anxiety in adults undergoing exodontia.

PMID- 22996479
TI  - Summary of: The signs and symptoms of tooth wear in a referred group of patients.

PMID- 22996480
TI  - Dental standards: fifty years of development.
AB  - Dental standards play a vital and important role in society by contributing to
      the quality and safety levels of products used in dental treatments by dental
      professionals as well as the hygiene products used by the general public. Few
      members of the public or indeed many dentists fully appreciate the contribution
      made by ISO international dental standards to the safety and quality of dental
      care. Further more the United Kingdom played a significant role in the
      establishment of the international standards organisation (ISO). The first two
      meetings of the dental international standards committee took place in England.
      In this article Derek W. Jones outlines the significant and important role played
      by the UK during the fifty years of dental international standards.

PMID- 22996481
TI  - Oral cancer - improving early detection and promoting prevention. Are you up to
      date?
AB  - Oral cancer is increasingly common. The need for early detection and promoting
      prevention is greater than ever and relevant to all who are responsible for the
      care of patients. Recent addition of oral cancer detection to the list of
      continuing professional development (CPD) topics recommended by the General
      Dental Council (GDC) reflects this importance.

PMID- 22996482
TI  - A general dental practitioner's view of the 90th General Session of the
      International Association of Dental Research.
AB  - A review of the 90th General Session of the International Association of Dental
      Research (IADR), held at Iguacu Falls, Brazil from 20-23 June 2012, from a
      delegate's perspective.

PMID- 22996505
TI  - Michael Pemberton: 'Oral cancer: we must continue to encourage restriction on
      tobacco and alcohol consumption'. Interviewed by Ruth Doherty.
AB  - Ruth Doherty, BDJ Managing Editor, spoke to Michael Pemberton, at the BDA
      Conference and Exhibition held in Manchester earlier this year.

PMID- 22996509
TI  - The signs and symptoms of tooth wear in a referred group of patients.
AB  - AIM: To determine the prevalence of signs and symptoms in a group of tooth wear
      patients referred to a hospital-based consultant clinic. METHOD: The clinical
      records of 290 patients referred to the Liverpool University Dental Hospital for
      tooth wear were reviewed retrospectively. A systematic sampling technique was
      used to select every alternate patient held on the consultant database. RESULTS:
      There were significantly more males than females in a ratio of 2.3:1.
      Significantly more males (56%) presented with severe tooth wear compared with
      females (31%) (p <0.001). Aesthetic concerns were the most prevalent presenting
      complaint (59%) and sensitivity was the second most common presenting complaint
      (40%). Functional problems and pain were less prevalent at 17% and 14%
      respectively. Subjects who had lost posterior support had more severe wear and
      more worn anterior teeth, which was statistically significant (p = 0.001). The
      proportion of subjects with undiagnosed apical pathology on worn teeth was 13%.
      CONCLUSIONS: Tooth wear predominated in males in this study. Patient
      dissatisfaction with appearance is the most common complaint and endodontic signs
      and symptoms are low in prevalence. Contrary to previous studies, lack of
      posterior support resulted in greater severity of wear, therefore restoring
      support is recommended.

PMID- 22996511
TI  - Social networks can spread the Olympic effect.

PMID- 22996510
TI  - Investigation of inhalational conscious sedation as a tool for reducing anxiety
      in adults undergoing exodontia.
AB  - AIM: To determine whether adult patients' dental anxiety levels decrease
      following exodontia carried out under inhalational conscious sedation with
      nitrous oxide and oxygen (IHS) and local anaesthetic (LA). DESIGN: Retrospective
      analysis of pre- and post-operative modified dental anxiety score (MDAS)
      questionnaires completed by patients treated in a primary care oral surgery
      service between 21 July 2010 and 17 December 2010. METHODOLOGY: 138 patients who
      had undergone exodontia were divided into three groups: moderate to severe
      anxiety (MDAS scores 11-25) treated under IHS and LA (n = 60), mild anxiety (MDAS
      scores 5-10) treated under IHS and LA (n = 43) and mixed anxiety (MDAS scores 5
      15) treated under LA only (n = 35). The mean pre- and post-operative MDAS scores
      were analysed by means of one-tailed, paired t-tests. RESULTS: The moderate to
      severely anxious group treated under IHS and LA showed a statistically
      significant decrease of 3.68 between the mean pre- and post-operative MDAS scores
      (p = 0.000). The IHS mildly anxious group showed a decrease of 0.07 (p = 0.392)
      and the LA group showed a decrease of 0.23 (p = 0.227). Neither of these results
      were statistically significant. CONCLUSION: These results support the use of IHS,
      to reduce anxiety of exodontia, in moderate to severely anxious adults undergoing
      minor oral surgery (MOS) procedures under LA in primary care oral surgery.

PMID- 22996522
TI  - Studies slow the human DNA clock.

PMID- 22996523
TI  - Lab-animal flights squeezed.

PMID- 22996524
TI  - Retraction record rocks community.

PMID- 22996525
TI  - UK technology-boost plan disappoints.

PMID- 22996526
TI  - The hidden threat of West Nile virus.

PMID- 22996527
TI  - Nano-safety studies urged in China.

PMID- 22996529
TI  - Laser centre lights up eastern Europe.

PMID- 22996530
TI  - Forest fires: Burn out.

PMID- 22996531
TI  - Neuroscience: Idle minds.

PMID- 22996532
TI  - Agriculture: Plant perennials to save Africa's soils.

PMID- 22996534
TI  - Astronomy: The United States must rejoin the SKA.

PMID- 22996538
TI  - Realizing talent: Arab science must help itself.

PMID- 22996539
TI  - World poverty: Sustainability is key to development goals.

PMID- 22996540
TI  - Preprint servers: no author fees.

PMID- 22996542
TI  - Renewables: Realizing Australia's bioenergy potential.

PMID- 22996543
TI  - Preprint servers: follow arXiv's lead.

PMID- 22996544
TI  - Neil Armstrong (1930-2012).

PMID- 22996545
TI  - Astronomy: Searching for the cosmic dawn.

PMID- 22996546
TI  - Neuroscience: Attention is more than meets the eye.

PMID- 22996547
TI  - Materials chemistry: Liposomes derived from molecular vases.

PMID- 22996549
TI  - Human behaviour: A cooperative instinct.

PMID- 22996550
TI  - Materials science: The matryoshka effect.

PMID- 22996551
TI  - Evolutionary biology: Insects converge on resistance.

PMID- 22996552
TI  - Bose glass and Mott glass of quasiparticles in a doped quantum magnet.
AB  - The low-temperature states of bosonic fluids exhibit fundamental quantum effects
      at the macroscopic scale: the best-known examples are Bose-Einstein condensation
      and superfluidity, which have been tested experimentally in a variety of
      different systems. When bosons interact, disorder can destroy condensation,
      leading to a 'Bose glass'. This phase has been very elusive in experiments owing
      to the absence of any broken symmetry and to the simultaneous absence of a finite
      energy gap in the spectrum. Here we report the observation of a Bose glass of
      field-induced magnetic quasiparticles in a doped quantum magnet (bromine-doped
      dichloro-tetrakis-thiourea-nickel, DTN). The physics of DTN in a magnetic field
      is equivalent to that of a lattice gas of bosons in the grand canonical ensemble;
      bromine doping introduces disorder into the hopping and interaction strength of
      the bosons, leading to their localization into a Bose glass down to zero field,
      where it becomes an incompressible Mott glass. The transition from the Bose glass
      (corresponding to a gapless spin liquid) to the Bose-Einstein condensate
      (corresponding to a magnetically ordered phase) is marked by a universal exponent
      that governs the scaling of the critical temperature with the applied field, in
      excellent agreement with theoretical predictions. Our study represents a
      quantitative experimental account of the universal features of disordered bosons
      in the grand canonical ensemble.

PMID- 22996554
TI  - A magnified young galaxy from about 500 million years after the Big Bang.
AB  - Re-ionization of the intergalactic medium occurred in the early Universe at
      redshift z ~ 6-11, following the formation of the first generation of stars.
      Those young galaxies (where the bulk of stars formed) at a cosmic age of less
      than about 500 million years (z ? 10) remain largely unexplored because they are
      at or beyond the sensitivity limits of existing large telescopes. Understanding
      the properties of these galaxies is critical to identifying the source of the
      radiation that re-ionized the intergalactic medium. Gravitational lensing by
      galaxy clusters allows the detection of high-redshift galaxies fainter than what
      otherwise could be found in the deepest images of the sky. Here we report
      multiband observations of the cluster MACS J1149+2223 that have revealed (with
      high probability) a gravitationally magnified galaxy from the early Universe, at
      a redshift of z = 9.6 +/- 0.2 (that is, a cosmic age of 490 +/- 15 million years,
      or 3.6 per cent of the age of the Universe). We estimate that it formed less than
      200 million years after the Big Bang (at the 95 per cent confidence level),
      implying a formation redshift of ?14. Given the small sky area that our
      observations cover, faint galaxies seem to be abundant at such a young cosmic
      age, suggesting that they may be the dominant source for the early re-ionization
      of the intergalactic medium.

PMID- 22996555
TI  - Pulsed electron paramagnetic resonance spectroscopy powered by a free-electron
      laser.
AB  - Electron paramagnetic resonance (EPR) spectroscopy interrogates unpaired electron
      spins in solids and liquids to reveal local structure and dynamics; for example,
      EPR has elucidated parts of the structure of protein complexes that other
      techniques in structural biology have not been able to reveal. EPR can also probe
      the interplay of light and electricity in organic solar cells and light-emitting
      diodes, and the origin of decoherence in condensed matter, which is of
      fundamental importance to the development of quantum information processors. Like
      nuclear magnetic resonance, EPR spectroscopy becomes more powerful at high
      magnetic fields and frequencies, and with excitation by coherent pulses rather
      than continuous waves. However, the difficulty of generating sequences of
      powerful pulses at frequencies above 100 gigahertz has, until now, confined high
      power pulsed EPR to magnetic fields of 3.5 teslas and below. Here we demonstrate
      that one-kilowatt pulses from a free-electron laser can power a pulsed EPR
      spectrometer at 240 gigahertz (8.5 teslas), providing transformative enhancements
      over the alternative, a state-of-the-art ~30-milliwatt solid-state source. Our
      spectrometer can rotate spin-1/2 electrons through pi/2 in only 6 nanoseconds
      (compared to 300 nanoseconds with the solid-state source). Fourier-transform EPR
      on nitrogen impurities in diamond demonstrates excitation and detection of EPR
      lines separated by about 200 megahertz. We measured decoherence times as short as
      63 nanoseconds, in a frozen solution of nitroxide free-radicals at temperatures
      as high as 190 kelvin. Both free-electron lasers and the quasi-optical technology
      developed for the spectrometer are scalable to frequencies well in excess of one
      terahertz, opening the way to high-power pulsed EPR spectroscopy up to the
      highest static magnetic fields currently available.

PMID- 22996553
TI  - An anatomically comprehensive atlas of the adult human brain transcriptome.
AB  - Neuroanatomically precise, genome-wide maps of transcript distributions are
      critical resources to complement genomic sequence data and to correlate
      functional and genetic brain architecture. Here we describe the generation and
      analysis of a transcriptional atlas of the adult human brain, comprising
      extensive histological analysis and comprehensive microarray profiling of ~900
      neuroanatomically precise subdivisions in two individuals. Transcriptional
      regulation varies enormously by anatomical location, with different regions and
      their constituent cell types displaying robust molecular signatures that are
      highly conserved between individuals. Analysis of differential gene expression
      and gene co-expression relationships demonstrates that brain-wide variation
      strongly reflects the distributions of major cell classes such as neurons,
      oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships
      between fine anatomical subdivisions are associated with discrete neuronal
      subtypes and genes involved with synaptic transmission. The neocortex displays a
      relatively homogeneous transcriptional pattern, but with distinct features
      associated selectively with primary sensorimotor cortices and with enriched
      frontal lobe expression. Notably, the spatial topography of the neocortex is
      strongly reflected in its molecular topography-the closer two cortical regions,
      the more similar their transcriptomes. This freely accessible online data
      resource forms a high-resolution transcriptional baseline for neurogenetic
      studies of normal and abnormal human brain function.

PMID- 22996556
TI  - High-performance bulk thermoelectrics with all-scale hierarchical architectures.
AB  - With about two-thirds of all used energy being lost as waste heat, there is a
      compelling need for high-performance thermoelectric materials that can directly
      and reversibly convert heat to electrical energy. However, the practical
      realization of thermoelectric materials is limited by their hitherto low figure
      of merit, ZT, which governs the Carnot efficiency according to the second law of
      thermodynamics. The recent successful strategy of nanostructuring to reduce
      thermal conductivity has achieved record-high ZT values in the range 1.5-1.8 at
      750-900 kelvin, but still falls short of the generally desired threshold value of
      2. Nanostructures in bulk thermoelectrics allow effective phonon scattering of a
      significant portion of the phonon spectrum, but phonons with long mean free paths
      remain largely unaffected. Here we show that heat-carrying phonons with long mean
      free paths can be scattered by controlling and fine-tuning the mesoscale
      architecture of nanostructured thermoelectric materials. Thus, by considering
      sources of scattering on all relevant length scales in a hierarchical fashion-
      from atomic-scale lattice disorder and nanoscale endotaxial precipitates to
      mesoscale grain boundaries--we achieve the maximum reduction in lattice thermal
      conductivity and a large enhancement in the thermoelectric performance of PbTe.
      By taking such a panoscopic approach to the scattering of heat-carrying phonons
      across integrated length scales, we go beyond nanostructuring and demonstrate a
      ZT value of ~2.2 at 915 kelvin in p-type PbTe endotaxially nanostructured with
      SrTe at a concentration of 4 mole per cent and mesostructured with powder
      processing and spark plasma sintering. This increase in ZT beyond the threshold
      of 2 highlights the role of, and need for, multiscale hierarchical architecture
      in controlling phonon scattering in bulk thermoelectrics, and offers a realistic
      prospect of the recovery of a significant portion of waste heat.

PMID- 22996557
TI  - Oceanic nitrogen reservoir regulated by plankton diversity and ocean circulation.
AB  - The average nitrogen-to-phosphorus ratio of marine phytoplankton (16N:1P) is
      closely matched to the nutrient content of mean ocean waters (14.3N:1P). This
      condition is thought to arise from biological control over the ocean's nitrogen
      budget, in which removal of bioavailable nitrogen by denitrifying bacteria
      ensures widespread selection for diazotrophic phytoplankton that replenish this
      essential nutrient when it limits the growth of other species. Here we show that
      in the context of a realistic ocean circulation model, and a uniform N:P ratio of
      plankton biomass, this feedback mechanism yields an oceanic nitrate deficit more
      than double its observed value. The critical missing phenomenon is diversity in
      the metabolic N:P requirement of phytoplankton, which has recently been shown to
      exhibit large-scale patterns associated with species composition. When we model
      these variations, such that diazotrophs compete with high N:P communities in
      subtropical regions, the ocean nitrogen inventory rises and may even exceed the
      average N:P ratio of plankton. The latter condition, previously considered
      impossible, is prevented in the modern ocean by shallow circulations that
      communicate stoichiometric signals from remote biomes dominated by diatoms with
      low N:P ratios. Large-scale patterns of plankton diversity and the circulation
      pathways connecting them are thus key factors determining the availability of
      fixed nitrogen in the ocean.

PMID- 22996558
TI  - Spontaneous giving and calculated greed.
AB  - Cooperation is central to human social behaviour. However, choosing to cooperate
      requires individuals to incur a personal cost to benefit others. Here we explore
      the cognitive basis of cooperative decision-making in humans using a dual-process
      framework. We ask whether people are predisposed towards selfishness, behaving
      cooperatively only through active self-control; or whether they are intuitively
      cooperative, with reflection and prospective reasoning favouring 'rational' self
      interest. To investigate this issue, we perform ten studies using economic games.
      We find that across a range of experimental designs, subjects who reach their
      decisions more quickly are more cooperative. Furthermore, forcing subjects to
      decide quickly increases contributions, whereas instructing them to reflect and
      forcing them to decide slowly decreases contributions. Finally, an induction that
      primes subjects to trust their intuitions increases contributions compared with
      an induction that promotes greater reflection. To explain these results, we
      propose that cooperation is intuitive because cooperative heuristics are
      developed in daily life where cooperation is typically advantageous. We then
      validate predictions generated by this proposed mechanism. Our results provide
      convergent evidence that intuition supports cooperation in social dilemmas, and
      that reflection can undermine these cooperative impulses.

PMID- 22996560
TI  - Intensified Arabian Sea tropical storms.

PMID- 22996562
TI  - 2D-oriented self-assembly of peptides induced by hydrated electrons.
AB  - Peptide assembly: a 2D peptide (Abeta16-22) film was produced successfully by
      introducing hydrated electrons into the assembly process of Abeta16-22. The
      interplay between experiment and theoretical calculation indicates that the film
      formation can be enhanced through the interactions between hydrated electrons and
      Abeta16-22.

PMID- 22996563
TI  - Simulation of the effects of complex-formation equilibria in electrophoresis:
      III. Simultaneous effects of chiral selector concentration and background
      electrolyte pH.
AB  - This paper describes the results of the second-level testing of the simulation
      program Simul 5 Complex. We compare the published experimental results with the
      simulated migration behavior of the enantiomers at different pH and chiral
      selector concentration values and use the same optimization object function,
      separation selectivity, as the original papers. Simul 5 Complex proved to be a
      suitable tool for the prediction of the effective mobilities, separation
      selectivities, and migration order reversals in these pH-dependent and CD
      concentration dependent enantiomer separations. In addition, by performing
      simulations of four different separations systems (both real and model systems),
      Simul 5 Complex revealed the existence of unexpected and hitherto unexplained
      electromigration dispersion effects that were caused by the complexation process
      itself and could significantly impair the quality of the separations.

PMID- 22996564
TI  - Influence of prescription monitoring programs on analgesic utilization by an
      insured retiree population.
AB  - PURPOSE: To estimate the association between prescription drug monitoring
      programs (PDMP) and the probability of analgesic use, overall and by analgesic
      type. METHODS: This cross-sectional study used 2007 Coordination of Benefits
      (COB) MarketScan administrative claims data of Medicare eligible and their
      dependents (n = 2 175 012). The exposure was PDMP status: no PDMP, electronic
      only PDMP (ePDMP), or electronic + paper PDMP (e + pPDMP). Outcomes included any
      analgesic use and, among users, analgesic use by schedule (CII, CIII, CIV, or CV
      Rx). Multivariable logistic and multinomial regressions were used to estimate the
      associations of PDMP status with any analgesic use and schedule of analgesic,
      respectively, controlling for sociodemographic and clinical factors. RESULTS:
      There were 834 489 (38.4%) subjects who received at least one analgesic; of
      these, 28.9% received one or more opioid analgesics (OAs). Compared to
      individuals in non-PDMP states, those living in PDMP states had increased odds of
      receiving any analgesic (OR(ePDMP)  = 1.19, 99%CI = 1.19, 1.20; OR(e+pPDMP)  =
      1.04, 99%CI = 1.03, 1.05). Among analgesic users, the odds of receiving potent
      CII analgesics relative to CV-Rx analgesics were lowest for individuals residing
      in e + pPDMP states (OR(e+pPDMP)  = 0.54, 99%CI = 0.53, 0.55), followed by ePDMP
      states (OR(ePDMP)  = 0.76, 99%CI = 0.75, 0.77) relative to non-PDMP states. The
      odds of receiving CIII OAs were highest for individuals in PDMP compared to non
      PDMP states. CONCLUSIONS: PDMPs are associated with reductions in utilization of
      targeted prescription OAs and increases in less scrutinized, lower scheduled OAs.
      Longitudinal studies are needed to determine how PDMPs shift analgesic
      prescribing and whether such shifts influence clinical care and economic
      outcomes.

PMID- 22996565
TI  - Stereochemical assignment of five new lignan glycosides from Viscum album by NMR
      study combined with CD spectroscopy.
AB  - The chemical study of the leaves and twigs of Viscum album led to the isolation
      of five new lignan glycosides, namely, ligalbumosides A-E (2-6) and one known
      lignan glycoside, alangilignoside C (1). The structures of five new lignan
      glycosides were determined to be (7R,8S,8'S)-4,9,4'-trihydroxy-3,5,3',5'
      tetramethoxy-7,9'-epoxylignan 9-O-beta-D-glucopyranoside (2), (7S,8S,7'S,8'R)
      4,9,4'-trihydroxy-3,5,3',5',7'-pentamethoxy-7,9'-epoxylignan 9-O-beta-D
      glucopyranoside (3), (7R,8R,7'S,8'S)-4,9,4'-trihydroxy-3,5,3',5',7'-pentamethoxy
      7,9'-epoxylignan 9-O-beta-D-glucopyranoside (4), (7S,8R,7'S,8'R)-4,9,4'
      trihydroxy-3,5,3',5',7'-pentamethoxy-7,9'-epoxylignan 9-O-beta-D-glucopyranoside
      (5), and (7R,8S,7'R,8'S)-4,9,4',7'-tetrahydroxy-3,5,3',5'-tetramethoxy-7,9'
      epoxylignan 9-O-beta-D-glucopyranoside (6) using 1D-, 2D-NMR, and CD spectra,
      chemical methods, as well as comparing the results with those reported in the
      literature.

PMID- 22996566
TI  - Nanoparticles for improved local retention after intra-articular injection into
      the knee joint.
AB  - PURPOSE: To evaluate using cationic polymeric nanoparticles that interact with
      hyaluronate to form ionically cross-linked hydrogels to increase the intra
      articular retention time of osteoarthritis drugs in the synovial cavity. METHODS:
      In vitro tests included nanoparticle release from cross-linked hydrogels using
      syringe and membrane dissolution tests, viscosity measurement of synovial fluid
      containing hydrogels, and release-rate measurement for a model active conjugated
      to a cationically substituted dextran using a hydrolyzable ester linkage in a
      sink dissolution test. Nanoparticle retention after intra-articular injection
      into rat knees was measured in vivo using fluorescence molecular tomography.
      RESULTS: Diffusional and convective transport of cationic nanoparticles from
      ionically cross-linked hydrogels formed in synovial fluid was slower in vitro
      than for uncharged nanoparticles. Hydrogels formed after the nanoparticles were
      mixed with synovial fluid did not appreciably alter the viscosity of the synovial
      fluid in vitro. In vitro release of a conjugated peptide from the cationic
      nanoparticles was approximately 20% per week. After intra-articular injection in
      rat knees, 70% of the nanoparticles were retained in the joint for 1 week.
      CONCLUSIONS: This study demonstrates the feasibility of using cationic polymeric
      nanoparticles to increase the retention of therapeutic agents in articular joints
      for indications such as osteoarthritis.

PMID- 22996568
TI  - Organ engineering--combining stem cells, biomaterials, and bioreactors to produce
      bioengineered organs for transplantation.
AB  - Often the only treatment available for patients suffering from diseased and
      injured organs is whole organ transplant. However, there is a severe shortage of
      donor organs for transplantation. The goal of organ engineering is to construct
      biological substitutes that will restore and maintain normal function in diseased
      and injured tissues. Recent progress in stem cell biology, biomaterials, and
      processes such as organ decellularization and electrospinning has resulted in the
      generation of bioengineered blood vessels, heart valves, livers, kidneys,
      bladders, and airways. Future advances that may have a significant impact for the
      field include safe methods to reprogram a patient's own cells to directly
      differentiate into functional replacement cell types. The subsequent combination
      of these cells with natural, synthetic and/or decellularized organ materials to
      generate functional tissue substitutes is a real possibility. This essay reviews
      the current progress, developments, and challenges facing researchers in their
      goal to create replacement tissues and organs for patients.

PMID- 22996567
TI  - Exploring the solid-form landscape of pharmaceutical hydrates: transformation
      pathways of the sodium naproxen anhydrate-hydrate system.
AB  - PURPOSE: To understand the transformation pathways amongst anhydrate/hydrate
      solid forms of sodium naproxen and to highlight the importance of a polymorphic
      dihydrate within this context. METHODS: Multi-temperature dynamic vapour sorption
      (DVS) analysis combined with variable-humidity X-ray powder diffraction (XRPD) to
      establish the transformation pathways as a function of temperature and humidity.
      XRPD and thermogravimetric analysis (TGA) to characterise bulk samples.
      Monitoring of in-situ dehydration using solid-state (13)C CP/MAS spectroscopy.
      RESULTS: At 25  degrees C, anhydrous sodium naproxen (AH) transforms directly to
      one dihydrate polymorph (DH-II). At 50  degrees C, AH transforms stepwise to a
      monohydrate (MH) then to the other dihydrate polymorph (DH-I). DH-II transforms
      to a tetrahydrate (TH) more readily than DH-I transforms to TH. Both dihydrate
      polymorphs transform to the same MH. CONCLUSIONS: The properties of the
      polymorphic dihydrate control the transformation pathways of sodium naproxen.

PMID- 22996569
TI  - Mapping and candidate-gene screening of the novel Turnip mosaic virus resistance
      gene retr02 in Chinese cabbage (Brassica rapa L.).
AB  - The extreme resistance to Turnip mosaic virus observed in the Chinese cabbage
      (Brassica rapa) line, BP8407, is monogenic and recessive. Bulked segregant
      analysis was carried out to identify simple sequence repeat and Indel markers
      linked to this recessive resistance gene, termed recessive Turnip mosaic virus
      resistance 02 (retr02). Mapping of PCR-specific Indel markers on 239 individuals
      of a BP8407 * Ji Zao Chun F(2) population, located this resistance gene to a 0.9
      cM interval between two Indel markers (BrID10694 and BrID101309) and in
      scaffold000060 or scaffold000104 on chromosome A04 of the B. rapa genome. Eleven
      eukaryotic initiation factor 4E (eIF4E) and 14 eukaryotic initiation factor 4G
      (eIF4G) genes are predicted in the B. rapa genome. A candidate gene, Bra035393 on
      scaffold000104, was predicted within the mapped resistance locus. The gene
      encodes the eIF(iso)4E protein. Bra035393 was sequenced in BP8407 and Ji Zao
      Chun. A polymorphism (A/G) was found in exon 3 between BP8407 and Ji Zao Chun.
      This gene was analysed in four resistant and three susceptible lines. A
      correlation was observed between the amino acid substitution (Gly/Asp) in the
      eIF(iso)4E protein and resistance/susceptibility. eIF(iso)4E has been shown
      previously to interact with the TuMV genome-linked protein, VPg.

PMID- 22996570
TI  - Disciplining doctors for misconduct: character matters, but so does competence.

PMID- 22996572
TI  - Cationic pentaheteroaryls as selective G-quadruplex ligands by solvent-free
      microwave-assisted synthesis.
AB  - We report herein a solvent-free and microwaved-assisted synthesis of several
      water soluble acyclic pentaheteroaryls containing 1,2,4-oxadiazole moieties (1
      7). Their binding interactions with DNA quadruplex structures were thoroughly
      investigated by FRET melting, fluorescent intercalator displacement assay (G4
      FID) and CD spectroscopy. Among the G-quadruplexes considered, attention was
      focused on telomeric repeats together with the proto-oncogenic c-kit sequences
      and the c-myc oncogene promoter. Compound 1, and to a lesser extent 2 and 5,
      preferentially stabilise an antiparallel structure of the telomeric DNA motif,
      and exhibit an opposite binding behaviour to structurally related polyoxazole
      (TOxaPy), and do not bind duplex DNA. The efficiency and selectivity of the
      binding process was remarkably controlled by the structure of the solubilising
      moieties.

PMID- 22996573
TI  - [Do cranberries protect against urinary tract infections?--There are still
      questions regarding the optimal dosage form and therapy].

PMID- 22996574
TI  - [Takes economy precedence over medical action?].

PMID- 22996575
TI  - [Renal sympathetic denervation--physical-antomical basics, procedure, and
      analysis of clinical and technical parameters on procedure success and efficacy].
AB  - BACKGROUND: Evidence from human and animal models indicate that excessive central
      sympathetic nerve activity (SNA) plays a pathogenic role in triggering and
      sustaining hypertension. Thus, treatments targeting this neurogenic (sympathetic)
      triggered hypertension were evaluated and renal sympathetic denervation (RND)
      showed promising results. However, little is known about the parameters
      influencing efficacy of high frequency energy in the arterial model. PATIENTS AND
      METHODS: Data from all 40 consecutive patients suffering from therapy-resistant
      hypertension who underwent RND and completed a 1-year follow-up were
      retrospectively analyzed. We focussed on procedural success, complications and
      efficacy (office-blood pressure, 24-h-blood pressure) and its correlations to
      quantity of ablations and intima media thickness. RESULTS: In all patients (65.9
      +/- 11.6 years (range 42-83); 72.5% male) the procedure was successful. Ablations
      with arterial access from the upper extremity were technically unsuccessful. With
      the use of 13.6 +/- 1.7 (10-17) ablations, office-blood pressure (1-year) could
      be reduced from 162/89 mmHg to 142/82 mmHg and 24-h-blood pressure from 149/83
      mmHg to 139/79 mmHg, respectively, including a medium to strong correlation to
      quantity of ablations (r = 0.57, r = 0.63) while documenting only a weak
      correlation to IMT (r = -0.29, r = -0.25). CONCLUSION: In comparison to the
      Simplicity studies, the hypertension lowering effects were less profound but
      consistently present over time in the 24-h-blood pressure assessments. The
      positive correlation of the quantity of ablations we found seems to be plausible
      regarding the unpredictable allocations of the sympathetic nerves i.e. in
      profoundly kinking vessels in hypertensives. The physics of high-frequency energy
      application in the arterial model needs further research.

PMID- 22996576
TI  - [Pulsatile tumor on the left side of the thorax after heart surgery].
AB  - HISTORY AND ADMISSION FINDINGS: In a 67-year-old woman a large haematoma
      developed on the left side of the chest after two sternotomies because of an
      aortic valve and aorta ascendens replacement for aortic type A dissection. After
      a few weeks, a pulsating mass remained over the 6th left parasternal intercostal
      space. A consultant general surgeon punctured the lesion and aspirated bright red
      blood. The patient was transferred for further diagnostic procedures to the
      cardiology department. INVESTIGATIONS: Ultrasound examination of the pulsating
      mass showed a 35 mm echo-free cavity with turbulent flow in the color Doppler. To
      clarify the inflow into this perfused cavity magnetic resonance imaging (MRI)
      with angiography of the thorax vessels was performed. The cavity was found to be
      a perfused pseudoaneurysm originating from the native left mammary artery. The
      aneurysm had a 6 mm long neck and a diameter of 35 mm. An interventional closure
      was planned. TREATMENT AND COURSE: With access via the right groin a 6 French
      LIMA guiding catheter was inserted into the origin of the left internal mammary
      artery. With a 0.014 inch Balance Middleweight coronary guide wire it was
      possible to engage the pseudoaneurysm. Over the wire, a tracker 18 infusion
      catheter was pushed down and placed in the pseudoaneurysm. The closure was
      performed by insertion of a 0.018 inch 3 cm/4 mm Hilal Microcoil into the
      aneurysm neck. The mammary artery was anatomically and functionally unaffected.
      After the deposit of a coil, the inflow was stopped. An ultrasound showed a blood
      coagulation in the pseudoaneurysm, which decreased in size over time. CONCLUSION:
      After sternotomy a pseudoaneurysm of the left internal mammary artery had
      developed. As a noninvasive imaging modalitiy the magnetic resonance angiography
      showed well the exact flow into the aneurysm and allowed the planning of the
      intervention. The closure was achieved with a microcoil with preservation of the
      native internal mammary artery.

PMID- 22996577
TI  - [Coronary CT angiography is superior to invasive coronary angiography--pro].

PMID- 22996578
TI  - [Coronary CT angiography is superior to invasive coronary angiography--contra].

PMID- 22996579
TI  - [New strategies for interventional and surgical therapy of atrial fibrillation].

PMID- 22996580
TI  - [18-year-old woman with post-partal cardiac arrest].

PMID- 22996581
TI  - [Fitness to drive in patients with implanted cardioverter-defibrillator].
AB  - A physician who takes care for patients with implanted cardioverter-defibrillator
      (ICD) must inform them about their fitness to drive since these patients carry a
      higher risk for the occurrence of syncope or sudden cardiac death at the wheel.
      The driver's license law in Germany does not mention patients with ICD. The
      fitness to drive of patients with ICD is covered by the Advisory Board for
      Traffic Medicine in Germany (Bundesanstalt fur Strabetaenwesen). These
      guidelines, however, are outdated and cannot be used to inform patients.
      Actually, these guidelines are under revision. Currently, the position paper of
      the German Society of Cardiology on "Fitness to drive and cardiovascular
      diseases" together with a recently published Dutch paper on this topic forms the
      basis of these recommendations. One week after ICD implantation for primary or
      one month after implantation for secondary prevention the patient may resume to
      drive. After adequate shocks the fitness to drive can be expected 2-4 months (3
      months) later. The assessment of the fitness to drive has to be performed
      individually, taking into account also possible other influencing factors. In
      individual cases it appears to be justified that patients with ICD work as
      professional drivers.

PMID- 22996582
TI  - [State of the art in carotid artery stenting 2012].
AB  - Stenosis of the internal carotid arteries is one of the leading causes of
      ischemic stroke. With increasing age of the general population, both physicians
      and patients have to increasingly face that problem, which is often found
      accidentally for example in the context of a routine checkup examination. In
      patients over seventy years, the incidence of carotid artery stenosis is about
      15%. Principally, there are three options for the treatment of carotid artery
      stenosis: 1) best medical treatment, 2) operative revision by endarterectomy and
      3) interventional therapy via stent implantation. Based on technical development
      and new scientific data, there has been tremendous progress of all three
      treatment strategies in the last few years. Therefore, the results of prior
      trials must not necessarily be considered when choosing a treatment option for
      the patient. The choice of therapy for the individual patient must take into
      account a number of criteria, such as grade of stenosis, symptoms, patient age,
      concomitant disease, anatomical conditions and patients' preference. Recently, a
      number of clinical trials have been performed to compare operative versus
      interventional treatment. The results of these studies led to some answers, but
      there are questions remaining which need to be clarified. The present article
      gives a brief overview and comment on the current status of treatment strategies
      of internal carotid artery stenosis based on the recent literature.

PMID- 22996583
TI  - [Surgery shortly after stent implantation?].

PMID- 22996584
TI  - MALDI TOF MS profiling of bacteria at the strain level: a review.
AB  - Since the advent of the use of matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight mass spectrometry (TOF MS) as a tool for microbial
      characterization, efforts to increase the taxonomic resolution of the approach
      have been made. The rapidity and efficacy of the approach have suggested
      applications in counter-bioterrorism, prevention of food contamination, and
      monitoring the spread of antibiotic-resistant bacteria. Strain-level resolution
      has been reported with diverse bacteria, using library-based and bioinformatics
      enabled approaches. Three types of characterization at the strain level have been
      reported: strain categorization, strain differentiation, and strain
      identification. Efforts to enhance the library-based approach have involved
      sample pre-treatment and data reduction strategies. Bioinformatics approaches
      have leveraged the ever-increasing amount of publicly available genomic and
      proteomic data to attain strain-level characterization. Bioinformatics-enabled
      strategies have facilitated strain characterization via intact biomarker
      identification, bottom-up, and top-down approaches. Rigorous quantitative and
      advanced statistical analyses have fostered success at the strain level with both
      approaches. Library-based approaches can be limited by effects of sample
      preparation and culture conditions on reproducibility, whereas bioinformatics
      enabled approaches are typically limited to bacteria, for which genetic and/or
      proteomic data are available. Biological molecules other than proteins produced
      in strain-specific manners, including lipids and lipopeptides, might represent
      other avenues by which strain-level resolution might be attained. Immunological
      and lectin-based chemistries have shown promise to enhance sensitivity and
      specificity. Whereas the limits of the taxonomic resolution of MALDI TOF MS
      profiling of bacteria appears bacterium-specific, recent data suggest that these
      limits might not yet have been reached.

PMID- 22996585
TI  - Sensory quality and appropriateness of raw and boiled Jerusalem artichoke tubers
      (Helianthus tuberosus L.).
AB  - BACKGROUND: The aim of the present study was to investigate the sensory
      attributes, dry matter and sugar content of five varieties of Jerusalem artichoke
      tubers and their relation to the appropriateness of the tubers for raw and boiled
      preparation. RESULTS: Sensory evaluation of raw and boiled Jerusalem artichoke
      tubers was performed by a trained sensory panel and a semi-trained consumer panel
      of 49 participants, who also evaluated the appropriateness of the tubers for raw
      and boiled preparation. The appropriateness of raw Jerusalem artichoke tubers was
      related to Jerusalem artichoke flavour, green nut flavour, sweetness and colour
      intensity, whereas the appropriateness of boiled tubers was related to celeriac
      aroma, sweet aroma, sweetness and colour intensity. In both preparations the
      variety Dwarf stood out from the others by being the least appropriate tuber.
      CONCLUSION: A few sensory attributes can be used as predictors of the
      appropriateness of Jerusalem artichoke tubers for raw and boiled consumption.
      Knowledge on the quality of raw and boiled Jerusalem artichoke tubers can be used
      to inform consumers on the right choice of raw material and thereby increase the
      consumption of the vegetable.

PMID- 22996586
TI  - MicroRNA-10a is involved in the metastatic process by regulating Eph tyrosine
      kinase receptor A4-mediated epithelial-mesenchymal transition and adhesion in
      hepatoma cells.
AB  - MicroRNAs (miRNAs) have been reported to be associated with the development of
      cancers. However, the function of miRNAs in human hepatocellular carcinoma (HCC)
      remains largely undefined. Here we found that overexpression of miR-10a promoted
      the migration and invasion of QGY-7703 and HepG2 cells in vitro but suppressed
      metastasis in vivo. Cell adhesion assays showed that miR-10a suppressed HCC cell
      matrix adhesion, which could explain the results of the in vivo animal
      experiments. The Eph tyrosine kinase receptor, EphA4, was identified as the
      direct and functional target gene of miR-10a. Knockdown of EphA4 phenocopied the
      effect of miR-10a and ectopic expression of EphA4 restored the effect of miR-10a
      on migration, invasion, and adhesion in HCC cells. We further demonstrated that
      miR-10a and EphA4 regulated the epithelial-mesenchymal transition process and the
      beta1-integrin pathway to affect cell invasion and adhesion. CONCLUSION: Our
      findings highlight the importance of miR-10a in regulating the metastatic
      properties of HCC by directly targeting EphA4 and may provide new insights into
      the pathogenesis of HCC.

PMID- 22996587
TI  - Naphthylhydrazone based selective and sensitive chemosensors for Cu2+ and their
      application in bioimaging.
AB  - Two new hydroxynaphthyl-hydrazone based fluorogenic chemosensors R1 and R2 have
      been synthesized by Schiff base condensation of Tris(4-formylphenyl)amine with 1
      hydroxynaphthalene-2-hydrazide and 1-hydroxynaphthalene-2-carbohydrazone,
      respectively. They are examined as highly selective and sensitive receptors for
      Cu2+ ions in aqueous medium. Electronic absorption as well as fluorescence
      titration studies of receptors R1 and R2 with different metal cations in
      H2O/CH3CN medium showed highly selective and very rapid (<2 min) binding affinity
      towards Cu2+ ions even in the presence of other commonly coexisting metal ions
      such as Na+, K+, Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Zn2+, Cd2+ and Hg2+.
      Quantification of the fluorescence titration analysis indicated that these newly
      synthesized receptors (R1 and R2) can indicate the presence of Cu2+ ions even at
      very low concentrations of 598 and 676 ppt, respectively. In addition, the
      propensity of these receptors as bio-imaging fluorescent probes to detect Cu2+
      ions in human cervical HeLa cancer cell lines and their cytotoxicity against HeLa
      cells have been investigated.

PMID- 22996588
TI  - Treatment of portosystemic shunt myelopathy with a stent graft deployed through a
      transjugular intrahepatic route.
AB  - A case of surgically created splenorenal shunt complicated with shunt myelopathy
      was successfully managed by placement of a stent graft within the splenic vein to
      close the portosystemic shunt and alleviate myelopathy. To our knowledge, this is
      the first report of a case of shunt myelopathy in a patient with noncirrhotic
      portal fibrosis without cirrhosis treated by a novel technique wherein a
      transjugular intrahepatic route was adopted to deploy the stent graft. 

PMID- 22996589
TI  - Dense accumulation of lipiodol emulsion in hepatocellular carcinoma nodule during
      selective balloon-occluded transarterial chemoembolization: measurement of
      balloon-occluded arterial stump pressure.
AB  - PURPOSE: To reveal the mechanism of dense accumulation of lipiodol emulsion (LE)
      in hepatocellular carcinoma (HCC) during selective balloon-occluded transarterial
      chemoembolization (B-TACE). METHODS: Balloon-occluded arterial stump pressure
      (BOASP) at the embolization portion was measured during selective B-TACE for 43
      nodules in 42 patients. Fluoroscopy and digital subtraction angiography were
      prospectively observed during selective B-TACE to note whether dense LE
      accumulation in HCC occurred. The LE concentration ratio of HCC to embolized
      liver parenchyma (LECHL ratio) was also calculated for each treatment on the
      basis of the computed tomographic scan obtained immediately after selective B
      TACE. The relationships between degree of LE accumulation and the BOASP, as well
      as the LECHL ratio, were analyzed. RESULTS: Arterial flow beyond the catheter tip
      was maintained even after balloon inflation. In 39 of 43 treatments, LE inflow
      into the nontumorous liver parenchyma ceased immediately after LE droplets were
      filled in arteries of the nontumorous liver parenchyma while LE inflow into the
      HCC nodule continued (group 1). More dense LE accumulation in HCC nodule was
      obtained in these 39 treatments. In four treatments, LE inflow both into the
      nontumorous liver parenchyma and into the HCC nodule continued, and no dense LE
      accumulation in HCC nodule was observed (group 2). In these four treatments,
      thick anastomotic vessels with collateral artery were noted. The BOASP in group 1
      was (mean +/- SD) 33.8 +/- 12.8 mmHg (range 13-64 mmHg) and that in group 2 was
      92.3 +/- 7.4 mmHg (range 83-100 mmHg). There was a statistically significant
      difference in BOASP between groups (p = 0.00004, Welch's t test). The LECHL ratio
      in group 1 was 18.3 +/- 13.9 (range 2.9-54.2) and that in group 2 was 2.6 +/- 1.1
      (range 1.7-4.2). There was a statistically significant difference in the LECHL
      ratio between the groups (p = 0.000034, Welch's t test). CONCLUSION: Selective B
      TACE induced dense LE accumulation in HCC nodules in 39 (91 %) of 43 treatments
      in which BOASP was 64 mmHg or less.

PMID- 22996590
TI  - Minimally invasive mutagenesis gives rise to a biosynthetic polyketide library.
AB  - Not in the public domain: Site-directed mutagenesis of megasynthases was the key
      to the generation of a library of polyketides in bacteria. Redox derivatizations
      are used to change the bioactivity profile of the compounds.

PMID- 22996591
TI  - 1H, 13C and 15N resonance assignments of wild-type Bacillus subtilis Lipase A and
      its mutant evolved towards thermostability.
AB  - Previously, we evolved Lipase A from Bacillus subtilis towards increased
      thermostability. The resulting mutant retains significant catalytic activity upon
      heating above 60  degrees C (and up to 100  degrees C) and cooling down, whereas
      wild-type lipase precipitates irreversibly and does not show significant activity
      in these conditions. Kinetic thermostability of proteins has not been
      characterized well on the molecular structure level so far, therefore our aim is
      to study it using NMR spectroscopy. Here, nearly complete (1)H, (13)C and (15)N
      resonance assignments are reported for wild-type and mutant Lipase A. Chemical
      shifts were used to predict secondary structure elements of both Lipase A
      variants.

PMID- 22996592
TI  - Kinetic and mechanistic differences in the interactions between caldendrin and
      calmodulin with AKAP79 suggest different roles in synaptic function.
AB  - The kinetic and mechanistic details of the interaction between caldendrin,
      calmodulin and the B-domain of AKAP79 were determined using a biosensor-based
      approach. Caldendrin was found to compete with calmodulin for binding at AKAP79,
      indicating overlapping binding sites. Although the AKAP79 affinities were similar
      for caldendrin (K(D) = 20 nM) and calmodulin (K(D) = 30 nM), their interaction
      characteristics were different. The calmodulin interaction was well described by
      a reversible one-step model, but was only detected in the presence of Ca(2+).
      Caldendrin interacted with a higher level of complexity, deduced to be an induced
      fit mechanism with a slow relaxation back to the initial encounter complex. It
      interacted with AKAP79 also in the absence of Ca(2+), but with different kinetic
      rate constants. The data are consistent with a similar initial Ca(2+)-dependent
      binding step for the two proteins. For caldendrin, a second Ca(2+)-independent
      rearrangement step follows, resulting in a stable complex. The study shows the
      importance of establishing the mechanism and kinetics of protein-protein
      interactions and that minor differences in the interaction of two homologous
      proteins can have major implications in their functional characteristics. These
      results are important for the further elucidation of the roles of caldendrin and
      calmodulin in synaptic function.

PMID- 22996593
TI  - Exploring the selectivity of a ligand complex with CDK2/CDK1: a molecular
      dynamics simulation approach.
AB  - Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery
      that govern the transition between phases during cell cycle progression.
      Abnormalities in CDKs activity and regulation are common features of cancer,
      making CDK family members attractive targets for the development of anticancer
      drugs. Their inhibitors have entered in clinical trials to treat cancer. Very
      recently, Heathcote et al. (J. Med. Chem. 2010, 53:8508-8522) have found a ligand
      BS194 that has a high affinity with CDK2 (IC(50) = 3 nM) but shows low affinity
      with CDK1 (IC(50) = 30 nM). To understand the selectivity, we used homology
      modeling, molecular docking, molecular dynamics, and free-energy calculation to
      analyze the interactions. A rational three-dimensional model of the CDK1/BS194
      complex is built. We found that Leu83 is a key residue that recognizes BS194 more
      effectively with CDK2 with good binding free energies rather than CDK1. Energetic
      analysis reveals that van der Waals interaction and non-polar contributions to
      solvent are favorable in the formation of complexes and amine group of the
      ligand, which plays a crucial role for binding selectivity between CDK2 and CDK1.

PMID- 22996571
TI  - 'Matching Michigan': a 2-year stepped interventional programme to minimise
      central venous catheter-blood stream infections in intensive care units in
      England.
AB  - BACKGROUND: Bloodstream infections from central venous catheters (CVC-BSIs)
      increase morbidity and costs in intensive care units (ICUs). Substantial
      reductions in CVC-BSI rates have been reported using a combination of technical
      and non-technical interventions. METHODS: We conducted a 2-year, four-cluster,
      stepped non-randomised study of technical and non-technical (behavioural)
      interventions to prevent CVC-BSIs in adult and paediatric ICUs in England. Random
      effects Poisson regression modelling was used to compare infection rates. A
      sample of ICUs participated in data verification. RESULTS: Of 223 ICUs in
      England, 215 (196 adult, 19 paediatric) submitted data on 2479 of 2787 possible
      months and 147 (66%) provided complete data. The exposure rate was 438 887 (404
      252 adult and 34 635 paediatric) CVC-patient days. Over 20 months, 1092 CVC-BSIs
      were reported. Of these, 884 (81%) were ICU acquired. For adult ICUs, the mean
      CVC-BSI rate decreased over 20 months from 3.7 in the first cluster to 1.48 CVC
      BSIs/1000 CVC-patient days (p<0.0001) for all clusters combined, and for
      paediatric ICUs from 5.65 to 2.89 (p=0.625). The trend for infection rate
      reduction did not accelerate following interventions training. CVC utilisation
      rates remained stable. Pre-ICU infections declined in parallel with ICU-acquired
      infections. Criterion-referenced case note review showed high agreement between
      adjudicators (kappa 0.706) but wide variation in blood culture sampling rates and
      CVC utilisation. Generic infection control practices varied widely. CONCLUSIONS:
      The marked reduction in CVC-BSI rates in English ICUs found in this study is
      likely part of a wider secular trend for a system-wide improvement in healthcare
      associated infections. Opportunities exist for greater harmonisation of infection
      control practices. Future studies should investigate causal mechanisms and
      contextual factors influencing the impact of interventions directed at improving
      patient care.

PMID- 22996594
TI  - Interaction of serum amyloid A with human cystatin C--identification of binding
      sites.
AB  - Serum amyloid A (SAA) is a multifunctional acute-phase protein whose natural role
      seems to be participation in many physiologic and pathological processes.
      Prolonged increased SAA level in a number of chronic inflammatory and neoplastic
      diseases gives rise to reactive systemic amyloid A amyloidosis, where the N
      terminal 76-amino acid residue-long segment of SAA is deposited as amyloid
      fibrils. Recently, a specific interaction between SAA and the ubiquitous
      inhibitor of cysteine proteases--human cystatin C (hCC)--has been described.
      Here, we report further evidence corroborating this interaction, and the
      identification of the SAA and hCC binding sites in the SAA-hCC complex, using a
      combination of selective proteolytic excision and high-resolution mass
      spectrometry. The shortest binding site in the SAA sequence was determined as
      SAA(86-104), whereas the binding site in hCC sequence was identified as hCC(96
      102). Binding specificities of both interacting sequences were ascertained by
      affinity experiments (ELISA) and by registration of mass spectrum of SAA-hCC
      complex.

PMID- 22996596
TI  - Juxtafacet cyst infection.
AB  - PURPOSE: In the realm of spinal surgery, infections have multiple etiologies and
      sites of origin. In this case series, we describe a juxtafacet cyst spinal
      infection that can often be missed or attributed to common symptomology of benign
      processes despite florid infection. METHODS: In rare instances, the juxtafacet
      cyst may become infected and require direct intervention. This case report
      attempts to describe the prodrome leading to such a diagnosis and two different
      ways to manage an infected facet cyst. RESULTS: Management of spinal infections
      varies due to the multiplicity of causes and location of infections. The
      juxtafacet cyst infection should remain a part of the differential diagnosis for
      low back pain as their presentation often mimics more common presenting
      complaints. CONCLUSIONS: In our two patient presentations, both were diabetics
      and had remote histories of cancer that necessitated chemotherapy or radiation
      therapy. They also seemingly had de novo onset of infected juxtafacet cyst. The
      variety of causes and presentations of spinal infections should heighten the
      astute surgeon to be suspicious of these entities and thus intervene early with
      appropriate management.

PMID- 22996598
TI  - Enhanced in vitro antitumor efficacy and strong anti-cell-migration activity of a
      hydroxycamptothecin-encapsulated magnetic nanovehicle.
AB  - A 10-hydroxycamptothecin-encapsulated magnetic nanovehicle (HEMN) was fabricated
      by coencapsulating Fe(3)O(4) nanoparticles and 10-hydroxycamptothecin (HCPT) into
      a micelle core self-assembled from the amphiphilic copolymer methoxy
      poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) through a facile dialysis
      method. A satisfactory drug-loading content of (9.03 +/- 0.67) % and a relatively
      high encapsulation efficiency of (53.52 +/- 6.46) % were achieved. In vitro drug
      release was performed by membrane dialysis and a pH-dependent release behavior
      was observed. In comparison with free HCPT dissolved in dimethylsulfoxide, HEMNs
      showed a greatly improved in vitro antitumor efficacy against three different
      human cancer cell lines-HeLa, A549, and HepG2-and lower IC(50) values were
      measured. The mechanism of cell death was investigated, and it was clearly
      demonstrated that the apoptosis process was triggered. An in vitro wound-healing
      assay and a transwell assay indicated that HEMNs exerted much stronger activity
      in inhibiting HeLa cell migration. The cellular uptake of HEMNs in a desired area
      can be significantly enhanced by an external magnetic field. These results
      demonstrate HCPT-encapsulated magnetic nanovehicles might have important
      potential in clinical applications for inhibiting tumor metastasis and for
      targeted drug delivery.

PMID- 22996597
TI  - Administered paricalcitol dose and survival in hemodialysis patients: a marginal
      structural model analysis.
AB  - PURPOSE: Several observational studies have indicated that vitamin D receptor
      activators (VDRA), including paricalcitol, are associated with greater survival
      in maintenance hemodialysis (MHD) patients. However, patients with higher serum
      parathyroid hormone, a surrogate of higher death risk, are usually given higher
      VDRA doses, which can lead to confounding by indication and attenuate the
      expected survival advantage of high VDRA doses. METHODS: We examined mortality
      predictability of low (>1 but <10 ug/week) versus high (>=10 ug/week) dose of
      administered paricalcitol over time in a contemporary cohort of 15 442 MHD
      patients (age 64 +/- 15 years, 55% men, 44% diabetes, 35% African-Americans) from
      all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow
      ups until 6/2007) using conventional Cox regression, propensity score (PS)
      matching, and marginal structural model (MSM) analyses. RESULTS: In our
      conventional Cox models and PS matching models, low dose of paricalcitol was not
      associated with mortality either in baseline (hazard ratio (HR): 1.03, 95%
      confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95%CI:(0.86-1.14)) or time
      dependent (HR: 1.04, 95%CI: (0.98-1.10)) and (HR: 1.12, 95%CI: (0.98-1.28))
      models, respectively. In contrast, compared to high dose of paricalcitol, low
      dose was associated with a 26% higher risk of mortality (HR: 1.26, 95%CI: (1.19
      1.35)) in MSM. The association between dose of paricalcitol and mortality was
      robust in almost all subgroups of patients using MSMs. CONCLUSIONS: Higher dose
      of paricalcitol appears causally associated with greater survival in MHD
      patients. Randomized controlled trials need to verify the survival effect of
      paricalcitol dose in MHD patients are indicated.

PMID- 22996599
TI  - Proliferation: Multitasking.

PMID- 22996600
TI  - Microenvironment: A dense danger.

PMID- 22996601
TI  - Metastasis: Recharging with COCO.

PMID- 22996604
TI  - Commentary on subgroup analysis in intervention research: opportunities for the
      public health approach to violence prevention.
AB  - The public health approach to prevention places a unique emphasis on
      understanding which populations are at greatest risk for poor health; the factors
      that place different populations at risk for experiencing injury, death,
      disability, and related health outcomes; the preventive interventions that are
      most effective for universal, selected, and indicated populations; and the best
      methods for encouraging the translation, dissemination, and adoption of
      preventive interventions for various populations. This information can be
      valuable in maximizing the efficiency and effectiveness of public health
      prevention approaches. The present article provides a commentary on the
      contributions of rigorous subgroup analysis to intervention research and, in
      particular, the Centers for Disease Control and Prevention's (CDC) public health
      approach to violence prevention.

PMID- 22996605
TI  - The metastatic cancer cell cortex: an adaptation to enhance robust cell division
      in novel environments?
AB  - To metastasize, cancer cells must be able to complete cell division in
      environments very different from their tissue of origin. We suggest that mitotic
      cell rounding, aided by several actin-regulatory oncogenes, may facilitate this
      process in a robust, context-independent manner.

PMID- 22996602
TI  - Tumorigenesis in Down's syndrome: big lessons from a small chromosome.
AB  - If assessed by a number of criteria for cancer predisposition, Down's syndrome
      (DS) should be an overwhelmingly cancer-prone condition. Although childhood
      leukaemias occur more frequently in DS, paradoxically, individuals with DS have a
      markedly lower incidence of most solid tumours. Understanding the mechanisms that
      are capable of overcoming such odds could potentially open new routes for cancer
      prevention and therapy. In this Opinion article, we discuss recent reports that
      suggest unique and only partially understood mechanisms behind this paradox,
      including tumour repression, anti-angiogenic effects and stem cell ageing and
      availability.

PMID- 22996603
TI  - Paths to stemness: building the ultimate antitumour T cell.
AB  - Stem cells are defined by the ability to self-renew and to generate
      differentiated progeny, qualities that are maintained by evolutionarily conserved
      pathways that can lead to cancer when deregulated. There is now evidence that
      these stem cell-like attributes and signalling pathways are also shared among
      subsets of mature memory T lymphocytes. We discuss how using stem cell-like T
      cells can overcome the limitations of current adoptive T cell therapies,
      including inefficient T cell engraftment, persistence and ability to mediate
      prolonged immune attack. Conferring stemness to antitumour T cells might unleash
      the full potential of cellular therapies.

PMID- 22996606
TI  - Respondent-driven sampling of Muslim undergraduate U.S. college students and
      alcohol use: pilot study.
AB  - PURPOSE: Prevention of alcohol abuse requires information about all demographic
      groups. However, little is known about drinking among people affiliated with
      proscriptive religions due to omission of religious affiliation in many surveys
      and challenges sampling them. Our objective was to pilot a sampling technique
      frequently used in the HIV literature, respondent-driven sampling, to assess
      potential association of alcohol use with religiosity, personal proscriptive
      belief, and social influences among Muslim U.S. college students. METHODS: Self
      identified Muslim undergraduate students (N = 156) at one urban commuter
      university completed a web-based survey. RESULTS: Prevalence adjusted for
      sampling was 9.1 % (95 % CI: 0.2-17.1 %) with in-group recruitment of 0.36 for
      drinkers and 0.43 for abstainers. In unadjusted analyses, students who were
      lifetime abstainers were more likely than drinkers to hold personal proscriptive
      belief and strongly agree with a measure of private religiosity. There was no
      difference on public religiosity measures between groups. Lifelong abstainers
      were more likely to report fewer students, fewer Muslim students, and fewer of
      their friends drank alcohol. They also were more likely to report that they
      attended high school with more Muslims and currently live in neighborhoods with
      more Muslims. CONCLUSIONS: In this pilot study, lifetime abstinence was
      associated with high private religiosity, personal proscriptive religious
      beliefs, and more proscriptive social influences. The findings suggest that
      respondent-driven sampling may be feasible in recruiting Muslim students.
      However, validation against other sampling techniques is needed.

PMID- 22996607
TI  - Socioeconomic disadvantage, mental disorders and risk of 12-month suicide
      ideation and attempt in the National Comorbidity Survey Replication (NCS-R) in
      US.
AB  - PURPOSE: We aim to explore the distinctive interrelationships between family
      income and mental disorders on suicidality in recent 12 months. METHODS: A
      stratified random subsample of adults in a household survey in US, National
      Comorbidity Survey Replication, was used for analyses. The ratio of family income
      to poverty threshold (RoFIPT) per capita was the primary predictor of interest to
      12-month occurrence of suicide ideation and attempt. Effect modification by
      mental disorders was further explored. RESULTS: A total of 4,724 subjects were
      analyzed. Inverse associations were found with RoFIPT for both suicidal outcomes
      after confounding control. Furthermore, effect modification was revealed that
      RoFIPT was more strongly associated with suicide ideation for those with mental
      disorders (OR 0.87; 95 % CI 0.79, 0.95). CONCLUSIONS: An inverse gradient of
      RoFIPT was shown with suicide ideation and attempt. Moreover, having mental
      disorders was found to be an effect modifier for the relationships between family
      income and suicidality.

PMID- 22996608
TI  - Wrapping an organic reducing reagent in a cationic boron complex and its use in
      the synthesis of polyhalide monoanionic networks.
AB  - The reaction between BF(3)?OEt(2) and one of two guanidines, 1,8
      bis(tetramethylguanidinyl)naphthalene (btmgn) and 1,2,4,5
      tetrakis(tetramethylguanidinyl)naphthalene (ttmgn), yields the salts
      [(btmgn)(BF(2))]BF(4) and [(ttmgn)(BF(2))(2)](BF(4))(2). NMR spectroscopic data
      show that the boron atoms in the cation and anion exchange in the case of
      [(ttmgn)(BF(2))(2)](BF(4))(2), but not in the case of [(btmgn)(BF(2))]BF(4). The
      rate constant for this exchange was estimated to be 4 s(-1) at 80  degrees C for
      solutions in CH(3)CN. These salts were subsequently used for the reduction of
      dihalides Br(2) or I(2) to give polyhalide salts. We report the synthesis and
      first complete characterization (including structural analysis) of salts that
      contain pentabromide monoanions. In these salts, the Br(5)(-) anions interact to
      give dimeric units or polymeric chains. Our results are compared to previous
      quantum chemical calculations on the gas-phase structure of the Br(5)(-) anion.
      The possible pathways that lead to the polyhalides are evaluated. In the case of
      [(ttmgn)(BF(2))(2)](BF(4))(2), reduction is accompanied by ttmgn oxidation,
      whereas in the case of [(btmgn)(BF(2))]BF(4) reduction is initiated by aromatic
      substitution.

PMID- 22996609
TI  - Determination of hydroxy acids in cosmetics by chemometric experimental design
      and cyclodextrin-modified capillary electrophoresis.
AB  - A CD-modified CE method was established for quantitative determination of seven
      hydroxy acids in cosmetic products. This method involved chemometric experimental
      design aspects, including fractional factorial design and central composite
      design. Chemometric experimental design was used to enhance the method's
      separation capability and to explore the interactions between parameters.
      Compared to the traditional investigation that uses multiple parameters, the
      method that used chemometric experimental design was less time-consuming and
      lower in cost. In this study, the influences of three experimental variables
      (phosphate concentration, surfactant concentration, and methanol percentage) on
      the experimental response were investigated by applying a chromatographic
      resolution statistic function. The optimized conditions were as follows: a
      running buffer of 150 mM phosphate solution (pH 7) containing 0.5 mM CTAB, 3 mM
      gamma-CD, and 25% methanol; 20 s sample injection at 0.5 psi; a separation
      voltage of -15 kV; temperature was set at 25 degrees C; and UV detection at 200
      nm. The seven hydroxy acids were well separated in less than 10 min. The LOD (S/N
      = 3) was 625 nM for both salicylic acid and mandelic acid. The correlation
      coefficient of the regression curve was greater than 0.998. The RSD and relative
      error values were all less than 9.21%. After optimization and validation, this
      simple and rapid analysis method was considered to be established and was
      successfully applied to several commercial cosmetic products.

PMID- 22996610
TI  - Multi-level evidence that circulating CK18 is a biomarker of tumour burden in
      colorectal cancer.
AB  - BACKGROUND: Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved
      cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent
      assays (ELISAs), respectively) are used as pharmacodynamic (PD) biomarkers of
      epithelial cell death in clinical trials. Having validated these ELISAs, we
      assessed their utility in colorectal cancer (CRC). METHODS: We applied the assays
      in several settings: 53 controls; 97 patients undergoing surgery and 74 patients
      with metastatic CRC undergoing chemotherapy (55 first line; 56 patients with
      repeated sampling through chemotherapy). Prognostic significance was evaluated
      using Kaplan-Meier life tables and Cox models; PD utility was assessed by
      analysis of repeated measures. RESULTS: Median cCK18 and tCK18 levels were
      elevated in patients with cancer (both P=0.0001), and among cancer patients,
      there were increasing trends from early to advanced stages (both
      P(trends)=0.0001). Increasing tCK18 predicted for reduced survival after surgery
      with curative intent (adjusted hazard ratio (HR) for doubling in concentration
      1.77, 95% CI: 1.04, 3.01) and after first-line chemotherapy in metastatic disease
      (adjusted HR per doubling in concentration=1.78, 95% CI: 1.37, 2.30). In patients
      with progressive disease during chemotherapy, repeated sampling revealed profiles
      with high baselines and progressive upwardly increases after cycle 1. CONCLUSION:
      This study provides evidence for cytokeratin 18 (CK18) as a prognostic and PD
      biomarker in patients with CRC and supports continued deployment of circulating
      CK18 in biomarker-enhanced trials.

PMID- 22996611
TI  - Routes to diagnosis for cancer - determining the patient journey using multiple
      routine data sets.
AB  - BACKGROUND: Cancer survival in England is lower than the European average, which
      has been at least partly attributed to later stage at diagnosis in English
      patients. There are substantial regional and demographic variations in cancer
      survival across England. The majority of patients are diagnosed following
      symptomatic or incidental presentation. This study defines a methodology by which
      the route the patient follows to the point of diagnosis can be categorised to
      examine demographic, organisational, service and personal reasons for delayed
      diagnosis. METHODS: Administrative Hospital Episode Statistics data are linked
      with Cancer Waiting Times data, data from the cancer screening programmes and
      cancer registration data. Using these data sets, every case of cancer registered
      in England, which was diagnosed in 2006-2008, is categorised into one of eight
      'Routes to Diagnosis'. RESULTS: Different cancer types show substantial
      differences between the proportion of cases that present by each route, in
      reasonable agreement with previous clinical studies. Patients presenting via
      Emergency routes have substantially lower 1-year relative survival. CONCLUSION:
      Linked cancer registration and administrative data can be used to robustly
      categorise the route to a cancer diagnosis for all patients. These categories can
      be used to enhance understanding of and explore possible reasons for delayed
      diagnosis.

PMID- 22996612
TI  - Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in
      patients with advanced solid tumours.
AB  - BACKGROUND: Axitinib, a potent and selective second-generation inhibitor of
      vascular endothelial growth factor receptors, enhanced the efficacy of
      chemotherapy in human xenograft tumour models. This phase I study investigated
      the safety, tolerability, pharmacokinetics and antitumour activity of axitinib
      combined with chemotherapy. METHODS: A total of 42 patients with advanced solid
      tumours received a continuous axitinib starting dose of 5 mg twice daily (b.i.d.)
      plus paclitaxel (90 mg m(-2) weekly), docetaxel (100 mg m(-2) every 3 weeks) or
      capecitabine (1000 or 1250 mg m(-2) b.i.d., days 1-14). RESULTS: Common treatment
      related adverse events across all cohorts were nausea (45.2%), hypertension
      (45.2%), fatigue (42.9%), diarrhoea (38.1%), decreased appetite (33.3%) and hand
      foot syndrome (31.0%). There was one complete response, nine partial responses
      and seven patients with stable disease. Ten patients (23.8%) remained on therapy
      for >8 months. Paclitaxel and capecitabine pharmacokinetics were similar in the
      absence or presence of axitinib, but docetaxel exposure was increased in the
      presence of axitinib. Axitinib pharmacokinetics were similar in the absence or
      presence of co-administered agents. CONCLUSIONS: Axitinib combined with
      paclitaxel or capecitabine was well tolerated; no additive increase in toxicities
      was observed. Antitumour activity was observed for each treatment regimen and
      across multiple tumour types.

PMID- 22996613
TI  - Interleukin-1alpha is the major alarmin of lung epithelial cells released during
      photodynamic therapy to induce inflammatory mediators in fibroblasts.
AB  - BACKGROUND: Photodynamic therapy (PDT) causes tissue damage that initiates a
      local inflammatory response. Post-PDT reactions are considered to assist in
      mobilising the immune system thereby affecting tumour recurrence. The initiating
      process of the PDT-dependent tissue reaction remains to be determined. METHODS:
      Primary cultures of human lung cells were established. The photoreaction mediated
      by pyropheophorbide-a, at specific subcellular sites and levels resulting in the
      release of alarmins by epithelial cells (Eps), was defined by immunoblot analyses
      and expression profiling. The activity of Ep-derived factors to stimulate
      expression of proinflammatory mediators, including IL-6, and to enhance
      neutrophil binding by fibroblasts (Fbs) was determined by functional bioassays.
      RESULTS: Epithelial cells release IL-1beta as the primary Fb-stimulatory activity
      under basal conditions. Intracellular IL-1alpha, externalised following
      photoreaction, accounts for most of the PDT-mediated Fb activation. Expression of
      IL-1 is subject to increase or loss during oncogenic transformation resulting in
      altered alarmin functions mobilisable by PDT. Photoreaction by a cell surface
      bound photosensitiser (PS) is 10-fold more effective than PSs localised to
      mitochondria or lysosomes. High-dose intracellular, but not cell surface,
      photoreaction inactivates IL-1 and reduces Fb stimulation. CONCLUSION: These in
      vitro data suggest that the subcellular site and intensity of photoreaction
      influence the magnitude of the stromal cell response to the local damage and, in
      part, support the relationship of PDT dose and level of post-PDT inflammatory
      response observed in vivo.

PMID- 22996615
TI  - Little hope for further innovations in psychopharmacology?

PMID- 22996614
TI  - Diabetes and breast cancer risk: a meta-analysis.
AB  - BACKGROUND: The potential of an increased risk of breast cancer in women with
      diabetes has been the subject of a great deal of recent research. METHODS: A meta
      analysis was undertaken using a random effects model to investigate the
      association between diabetes and breast cancer risk. RESULTS: Thirty-nine
      independent risk estimates were available from observational epidemiological
      studies. The summary relative risk (SRR) for breast cancer in women with diabetes
      was 1.27 (95% confidence interval (CI), 1.16-1.39) with no evidence of
      publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12
      1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13-1.63)). Type 1
      diabetes, or diabetes in pre-menopausal women, were not associated with risk of
      breast cancer (SRR 1.00 (95% CI, 0.74-1.35) and SRR 0.86 (95% CI, 0.66-1.12),
      respectively). Studies adjusting for body mass index (BMI) showed lower estimates
      (SRR 1.16 (95% CI, 1.08-1.24)) as compared with those studies that were not
      adjusted for BMI (SRR 1.33 (95% CI, 1.18-1.51)). CONCLUSION: The risk of breast
      cancer in women with type 2 diabetes is increased by 27%, a figure that decreased
      to 16% after adjustment for BMI. No increased risk was seen for women at pre
      menopausal ages or with type 1 diabetes.

PMID- 22996616
TI  - A retrospective study of clinical usage of quetiapine XR and quetiapine IR in
      outpatients with schizophrenia in Denmark.
AB  - OBJECTIVES: The atypical antipsychotic quetiapine is a first-line treatment for
      schizophrenia. This non-interventional study (NCT01212575) evaluated the clinical
      use of its two formulations, extended release (XR) and immediate release (IR), in
      outpatients with schizophrenia spectrum disorder. METHODS: Patients who had
      received at least one dose of quetiapine XR and/or IR were included. A dosage
      >=400 mg/day was defined as antipsychotic. Medical records data were collected
      retrospectively. RESULTS: Of 186 enrolled patients, 99 (53%) and 87 (47%)
      received quetiapine XR and IR, respectively. Use in antipsychotic dosage was seen
      for 89% XR versus 63% IR patients (mean daily dose >=400 mg/day; p < 0.0001). 75%
      XR and 53% IR patients used dosages >=600 mg/day (p = 0.0019). Quetiapine XR was
      used at higher mean daily dosages than IR (748 vs 566 mg/day; p = 0.006). Forty
      three patients (23%) used both formulations concomitantly; 55 patients (30%) used
      either XR or IR. Quetiapine IR was used as-needed in 44 patients (23%); one
      patient used XR as-needed. CONCLUSIONS: Quetiapine XR was used more often in
      higher (antipsychotic) dosages; quetiapine IR more frequently on an as-needed
      administration basis. Concomitant use was seen. These findings probably reflect
      the different profiles of XR/IR and advocate the need for both formulations to
      offer treatment choice.

PMID- 22996617
TI  - Semantic priming and verbal learning in current opiate users, ex-users and non
      user controls.
AB  - OBJECTIVE: Despite a growing interest in memory functions of chronic drug users,
      investigation of semantic and episodic memory in opiate users is limited, and
      findings of studies have been inconsistent. The present study aimed to assess
      semantic memory and episodic memory for both drug-related and neutral stimuli in
      current and ex-users of opiates. METHODS: Using an independent group design, we
      assessed semantic priming and verbal learning in 16 current opiate users on a
      methadone maintenance programme, 16 ex-opiate users in rehabilitation programmes
      and 16 healthy controls. The groups were matched on verbal IQ, age and employment
      status. RESULTS: We found that current and ex-users showed intact automatic and
      controlled semantic priming. Ex-users who had been abstinent for an average of 19
      months showed a verbal learning impairment compared with controls. Both current
      and ex-users were impaired in recalling semantically unrelated words but
      unimpaired in recalling semantically related words. CONCLUSION: The findings
      suggest a relative lack of spontaneous use of mnemonic strategies and imply that
      highly structured information would help opiate-using clients in treatment.

PMID- 22996618
TI  - Plasma amisulpride in relation to prescribed dose, clozapine augmentation, and
      other factors: data from a therapeutic drug monitoring service, 2002-2010.
AB  - OBJECTIVE: This study aimed to investigate the effect of dose and other factors
      on plasma amisulpride concentrations in clinical practice. METHOD: Amisulpride
      therapeutic drug monitoring data 2002-2010 have been studied. RESULTS: There were
      296 samples (196 adult patients). Amisulpride was not detected in 10% of samples.
      In the remainder, the mean plasma amisulpride in relation to the prescribed dose
      (mg/day) was as follows: 100-200 (111 ug/L), 201-400 (254 ug/L), 400-800 (421
      ug/L), and 800-1200 (494 ug/L). For prescribed doses up to 800 mg/day, only 51%
      of results were within 100-319 ug/L. There were no significant sex differences in
      mean plasma amisulpride or mean dose. The mean plasma amisulpride, but not the
      dose, was significantly higher in smokers. Linear regression analysis showed that
      dose explained only 42% of the variation in plasma amisulpride after log(10)
      transformation of both variables. There was no significant difference in the mean
      dose or mean plasma amisulpride in patients co-prescribed clozapine as compared
      with the remaining samples. CONCLUSION: In practice, dose is a poor predictor of
      plasma amisulpride concentration. Therapeutic drug monitoring may not only help
      assess adherence, but also guide dosage.

PMID- 22996619
TI  - Metabolic syndrome in psychiatrically hospitalized patients treated with
      antipsychotics and other psychotropics.
AB  - OBJECTIVE: We evaluated prevalence and risk factors for metabolic syndrome in
      inpatients treated with antipsychotics, with or without other psychotropic drugs.
      Although the literature on metabolic syndrome in psychiatry has expanded in
      recent years, we seek to elucidate some of the remaining gaps by examining a
      severely and chronically ill population heavily treated with pharmacological
      agents. METHODS: With data from medical records of 589 adults hospitalized at
      McLean Hospital in 2010 and 2011, we used standard statistical analyses to
      characterize risks and covariates of metabolic syndrome. RESULTS: With prior
      antipsychotic treatment, prevalence of metabolic syndrome was 29.5%. The syndrome
      was strongly associated with being overweight (>=25 kg/m(2) in 60.1% of
      subjects), older age, longer treatment-exposure, schizoaffective diagnosis
      (39.8%), more illness-episodes or hospitalizations, polytherapy, and higher total
      daily chlorpromazine-equivalent doses, but not sex. Notably, metabolic syndrome
      risk was greater among young, antipsychotic treated patients (15.5-fold at age
      <=25 years). CONCLUSIONS: The findings extend information on the association of
      metabolic syndrome with antipsychotic treatment. Metabolic syndrome was found in
      30% of antipsychotic-exposed inpatients. Risk was surprisingly high in young
      persons and after brief treatment-exposure, and psychotropic polytherapy
      increased risk.

PMID- 22996620
TI  - The effect of probiotic-fermented soy milk on enhancing the NO-mediated vascular
      relaxation factors.
AB  - BACKGROUND: Soy milk is one of the common soy-based foods in Asia. In this study
      the effects of soy milk fermented with selected probiotics on nitric oxide (NO)
      mediated vascular relaxation factors in cell model systems were investigated.
      RESULTS: Soy milk fermented with Lactobacillus plantarum TWK10 or Streptococcus
      thermophilus BCRC 14085 for 48 h showed a greater transformation of glucoside
      isoflavones to aglycone isoflavones (P < 0.05). An increase in aglycone
      isoflavones in ethanol extracts from fermented soy milk stimulated NO production
      and endothelial NO synthase (eNOS) activity in human umbilical vein endothelial
      cells. It also had a stimulating effect on superoxide anion scavenging and
      prostaglandin E2 production. In addition, it enhanced mRNA expression of the E
      prostanoid 4 receptor in rat thoracic aorta smooth muscle cells. Moreover, a
      small amount of O2- induced by water extracts from fermented soy milk at low
      concentration (1 mg mL-1) increased the content of calcium ions and activated
      eNOS, thereby promoting NO production and the coupling state of eNOS. CONCLUSION:
      Soy milk fermented with selected probiotics promotes the relaxation factors of
      vascular endothelial cells and can be applied in the development of functional
      foods.

PMID- 22996622
TI  - Hepatic fat loss in advanced nonalcoholic steatohepatitis: are alterations in
      serum adiponectin the cause?
AB  - Advanced liver fibrosis in nonalcoholic steatohepatitis (NASH) is often
      accompanied by a reduction in hepatic fat to the point of complete fat loss
      (burnt-out NASH), but the mechanisms behind this phenomenon have not been
      elucidated. Adiponectin is raised in cirrhosis of any cause and has potent
      antisteatotic activity. In this study we examined 65 patients with advanced
      biopsy-proven NASH (fibrosis stage 3-4) and 54 with mild disease (fibrosis stage
      0-1) to determine if disappearance of steatosis correlated with changes in serum
      adiponectin. All patents had fasting blood tests and anthropometric measures at
      the time of liver biopsy. Liver fat was accurately quantitated by morphometry.
      Serum adiponectin was measured by immunoassay. When compared to those with early
      disease, patients with advanced NASH were more insulin-resistant, viscerally
      obese, and older, but there was no difference in liver fat content or adiponectin
      levels. Adiponectin had a significant negative correlation with liver fat
      percentage in the whole cohort (r = -0.28, P < 0.01), driven by patients with
      advanced NASH (r = -0.40, P < 0.01). In advanced NASH, for each 4 MUg/L increase
      in adiponectin there was an odds ratio OR of 2.0 (95% confidence interval [CI]:
      1.3-3.0, P < 0.01) for a 5% reduction in hepatic fat. Adiponectin was highly and
      significantly associated with almost complete hepatic fat loss or burnt-out NASH
      (12.1 versus 7.4 MUg/L, P = 0.001) on multivariate analysis. A relationship
      between adiponectin, bile acids, and adipocyte fexaramine activation was
      demonstrated in vivo and in vitro, suggestive of hepatocyte-adipocyte crosstalk.
      CONCLUSION: Serum adiponectin levels in advanced NASH are independently
      associated with hepatic fat loss. Adiponectin may in part be responsible for the
      paradox of burnt-out NASH. (HEPATOLOGY 2012).

PMID- 22996623
TI  - Concerns regarding the interpretation of fatty fish intake and type 2 diabetes in
      the EPIC-InterAct Study.

PMID- 22996624
TI  - Dietary acid load and risk of hypertension.

PMID- 22996625
TI  - Should dietary SFA be exchanged for linoleic acid?

PMID- 22996627
TI  - Claims about women's use of non-fatal force in intimate relationships: a
      contextual review of Canadian research.
AB  - Claims that violence is gender-neutral are increasingly becoming "common sense"
      in Canada. Antifeminist groups assert that the high rates of woman abuse
      uncovered by major Canadian national surveys conducted in the early 1990s are
      greatly exaggerated and that women are as violent as men. The production of
      degendered rhetoric about "intimate partner violence" contributes to claims that
      women's and men's violence is symmetrical and mutual. This article critically
      evaluates common claims about Canadian women's use of nonlethal force in
      heterosexual intimate relationships in the context of the political struggle over
      the hegemonic frame for violence and abuse. The extant Canadian research
      documenting significant sex differences in violence and abuse against adult
      intimate partners is reviewed.

PMID- 22996621
TI  - Mass spectrometry imaging under ambient conditions.
AB  - Mass spectrometry imaging (MSI) has emerged as an important tool in the last
      decade and it is beginning to show potential to provide new information in many
      fields owing to its unique ability to acquire molecularly specific images and to
      provide multiplexed information, without the need for labeling or staining. In
      MSI, the chemical identity of molecules present on a surface is investigated as a
      function of spatial distribution. In addition to now standard methods involving
      MSI in vacuum, recently developed ambient ionization techniques allow MSI to be
      performed under atmospheric pressure on untreated samples outside the mass
      spectrometer. Here we review recent developments and applications of MSI
      emphasizing the ambient ionization techniques of desorption electrospray
      ionization (DESI), laser ablation electrospray ionization (LAESI), probe
      electrospray ionization (PESI), desorption atmospheric pressure photoionization
      (DAPPI), femtosecond laser desorption ionization (fs-LDI), laser electrospray
      mass spectrometry (LEMS), infrared laser ablation metastable-induced chemical
      ionization (IR-LAMICI), liquid microjunction surface sampling probe mass
      spectrometry (LMJ-SSP MS), nanospray desorption electrospray ionization (nano
      DESI), and plasma sources such as the low temperature plasma (LTP) probe and
      laser ablation coupled to flowing atmospheric-pressure afterglow (LA-FAPA).
      Included are discussions of some of the features of ambient MSI for example the
      ability to implement chemical reactions with the goal of providing high abundance
      ions characteristic of specific compounds of interest and the use of tandem mass
      spectrometry to either map the distribution of targeted molecules with high
      specificity or to provide additional MS information on the structural
      identification of compounds. We also describe the role of bioinformatics in
      acquiring and interpreting the chemical and spatial information obtained through
      MSI, especially in biological applications for tissue diagnostic purposes.
      Finally, we discuss the challenges in ambient MSI and include perspectives on the
      future of the field.

PMID- 22996628
TI  - Physical tactics of female partners against male batterer program participants.
AB  - Descriptive and predictive analyses were conducted using a multisite database of
      batterer program participants to assess the nature and extent of their female
      partner's violence, and implications for batterer program outcome (N = 563).
      Approximately 40% of the women reported ever using "severe" conflict tactics on
      the Conflict Tactics Scale (CTS; 17% used severe tactics in the arrest incident).
      Approximately 20% of the women reported using any type of physical tactic during
      a 15-month follow-up, and nearly all of these women were with men who physically
      attacked them during that period. These women were also highly likely to report
      acting out of fear or self-defense, and having sought a variety of services to
      deal with the men's violence. Their male partners, furthermore, showed evidence
      of antisocial tendencies and alcohol problems. Overall, the findings suggest
      women's "violent resistance" rather than "mutuality and symmetry." Batterer
      programs appear more appropriate in this regard than couples counseling.

PMID- 22996630
TI  - Self-defense among women with disabilities: an unexplored domain in domestic
      violence cases.
AB  - Women with disabilities are frequent victims of domestic violence, yet scant
      research has examined self-protective mechanisms that could mitigate this abuse.
      This article reviews prevalence and types of intimate partner violence against
      women with disabilities and explores the factors that leave this population at
      higher risk for abuse than nondisabled women. Barriers to self-protection against
      domestic violence for women with diverse disabilities are highlighted and the use
      of nonfatal force as self-defense is explored. A case example and considerations
      for enhancing self-protection strategies for women with disabilities experiencing
      intimate partner violence are provided.

PMID- 22996629
TI  - Portrayal of women as intimate partner domestic violence perpetrators.
AB  - The article explores some of the ways heterosexual women are portrayed as
      perpetrators of intimate partner domestic violence (IPV) in police domestic
      violence records in England and is the first study in the United Kingdom to
      examine the issue of gender and domestic violence perpetrators in any detail and
      over time. The article is based on a study of 128 IPV cases tracked
      longitudinally over 6 years, including 32 cases where women were the sole
      perpetrators and a further 32 cases where women were "dual" perpetrators
      alongside men. Women were 3 times more likely than men to be arrested when they
      were construed as the perpetrator. However, Pence and Dasgupta's category of
      "pathological violence" appeared more useful as an analytical category in the
      construction of women as "perpetrators" and men as "victims" than the notion of
      "battering."

PMID- 22996631
TI  - [IOL multifocality combined with the compensation for corneal spherical
      aberration: a new concept of presbyopia correcting IOL].
AB  - Further developments in the field of intraocular lenses have resulted in
      improvements of multifocal lenses (MIOL) which enable spectacle-free vision at
      near and far distance under most conditions. In our prospective study we
      investigated a new aberration-corrected MIOL, whereby 31 eyes of 19 patients,
      aged between 40 and 81 years, received a Tecnis ZMB00 MIOL (Abbott Medical
      Optics). Postoperative visual results were documented. Patients were enrolled if
      they were at least 40 years old and if they were scheduled for cataract surgery
      or presbyobic lens exchange. Exclusion criteria were any other visually relevant
      pathologies and a corneal astigmatism of 1.5 D or more. After 6 months, 94.7 % of
      the patients had a binocular uncorrected distance vision of 0.1 LogMAR or better,
      67.7 % of eyes could read Jaeger 1+ (0.0 LogMAR) and 93.6 % could read Jaeger 1
      (0.1 LogMAR) or better. There was no correlation between the power of the
      implanted lens and the postoperative distance or near vision or between IOL power
      and best-corrected distance vision. The aspheric diffractive multifocal IOL
      Tecnis ZMB00 provides a restoration of far and near visual function after
      cataract surgery or presbyopia correction. The correction provided by the IOL is
      predictable and independent from the optical power of the IOL implanted. The
      combination of diffractive multifocality and compensation for corneal spherical
      aberration is an effective alternative for cataract surgery and presbyopia
      correction.

PMID- 22996632
TI  - [Managing unexplained visual loss--a "quick guide"].
AB  - Optic neuritis and anterior ischaemic optic neuropathy (AION) present with acute
      visual loss. AION shows a swollen optic disc, in optic neuritis it may be swollen
      in one third of the patients. Optic neuritis patients complain usually about pain
      with eye movements. A tumour causes slowly progressive visual loss, mostly
      painless. In all these cases a relative afferent pupillary defect (RAPD) may be
      expected. If RAPD is missing, a problem of the optic media (retinoscopy, pinhole
      test), macular disease (micropsy, improvement with grey filters), amblyopia or
      non-organic visual loss can be causative. However, it has to be considered that a
      homonymous visual field defect may be perceived as an unilateral visual loss.
      Therefore visual field testing is necessary.

PMID- 22996633
TI  - [Macrophages in the ultrastructure of PDR membranes and subretinal AMD membranes-
      a possible role in neoangiogenesis].
AB  - BACKGROUND AND PURPOSE: Proliferative diabetic retinopathy (PDR) and age-related
      macular degeneration (AMD) are sight-threatening diseases with high social
      impact. The aim of our study is to compare the ultrastructure of PDR membranes
      and those in AMD with a special focus on the macrophages. MATERIAL AND METHODS:
      In our study 24 PDR patients and 11 AMD patients were enrolled. They all
      underwent complete ophthalmological examination including OCT. In all cases pars
      plana vitrectomy with excision of epiretinal or subretinal membranes was
      performed. Proliferations taken directly from the eye have been studied by
      transmission and scanning electron microscopy and with safranin O. RESULTS: The
      fibrovascular proliferations in PDR consisted mostly of fibroblasts and
      occasional macrophages near the blood vessels. The prevailing type of blood
      vessels had one thin layer of endothelial cells, very thin basal membrane and no
      pericytes. Subretinal membranes in AMD patients consisted mainly of fibroblasts,
      isolated RPE cells and elements of the blood. Numerous macrophages and leukocytes
      in groups and clusters were found around the capillaries of subretinal blood
      vessels. The cells showed some peculiarities: diminished number of pseudopodia,
      altered shape. Groups of cytofilaments became visible in macrophages cell
      periphery. The number of proteoglycans in the matrix was increased. CONCLUSION:
      Our results point out that macrophages play a key role in the formation of the
      fibrovascular proliferations in both PDR and AMD. Inflammation is assumed to act
      in the pathogenesis of both diseases. Probably the senescence of macrophages,
      which we found in our study, is responsible for their proangiogenic response and
      promotion of new vessel formation. It is reasonable to expect that anti
      inflammatory therapy might be helpful in patients with AMD and PDR.

PMID- 22996634
TI  - [The subnuclei of the oculomotor nucleus in humans].
AB  - Examinations of eye movements offer an easy clinical method for the diagnosis of
      disturbances in the pathways for the generation of eye movements including the
      extraocular and inner eye muscles. A prerequisite is a good knowledge of the
      anatomy of the pathways for the generation of eye movements. The oculomotor
      nucleus represents an important relay station, which contains not only the
      motoneurons of four extraocular muscles and the levator palpebrae muscle, but
      also the preganglionic neurons of the ciliary ganglion for the mediation of the
      pupillary and accommodation response. Recent work about the special anatomy of
      the extraocular muscles and histochemical findings about the neurons in the
      Edinger-Westphal nucleus (EW), which indicated that this nucleus does not contain
      the preganglionic neurons of the ciliary ganglion, led to a new, modified map of
      the oculomotor nucleus complex. The most serious alteration refers to the
      location of the preganglionic neurons, which form a group of scattered neurons
      outside of the EW and now are termed EWpg. In contrast, the traditional
      cytoarchitectonically defined EW in the human eye contains peptidergic neurons
      with a completely different function, e.g., stress related, and is therefore
      termed EWcp (centrally projecting). A knowledge about the exact locations of
      extraocular motoneurons and preganglionic neurons is essential for the correct
      interpretation of clinico-anatomic findings.

PMID- 22996635
TI  - Bortezomib suppresses the growth of leukemia cells with Notch1 overexpression in
      vivo and in vitro.
AB  - Bortezomib has been widely used in the treatment of various cancers; however, its
      exact mechanisms of action are not fully understood, particularly in acute T
      lymphoblast leukemia (T-ALL). Here, we visualize the anti-leukemia effect of
      bortezomib in both human T-ALL cell line and animal models. In vitro study, a
      human T-ALL cell line bearing Notch1 mutations, MOLT-4, was treated with
      bortezomib. At clinically achievable concentrations, bortezomib inhibited cell
      growth by inducing G1 phase arrest and apoptosis with a dose-dependent manner. A
      murine tumor xenograft model was achieved by subcutaneous injection of MOLT-4
      cells for in vivo study. Administration of bortezomib significantly reduced tumor
      mass volume when compared with controls. Of note, bortezomib inhibited growth of
      leukemia cells in a Notch1-induced murine T-ALL model, and the life span of
      leukemia-bearing mice was markedly increased. Further studies revealed that
      bortezomib led to inhibited expression of Notch1 target genes. Taken together,
      our results demonstrate that bortezomib shows significant anti-leukemia effect in
      T-ALL bearing Notch1 mutations in vitro and in vivo. The present study provides
      evidence that bortezomib might be a candidate therapeutic reagent in the
      treatment of T-ALL.

PMID- 22996636
TI  - A thermodynamic and kinetic study of the heterolytic activation of hydrogen by
      frustrated borane-amine Lewis pairs.
AB  - Calorimetry is used to measure the reaction enthalpies of hydrogen (H(2))
      activation by 2,6-lutidine (Lut), 2,2,6,6-tetramethylpiperidine (TMP), N-methyl
      2,2,6,6-tetramethylpiperidine (MeTMP), and tri-tert-butylphosphine (TBP) with
      tris(pentafluorophenyl)borane (BCF). At 6.6 bar H(2) the conversion of the Lewis
      acid Lewis base pair to the corresponding ionic pair in bromobenzene at 294 K was
      quantitative in under 60 min. Integration of the heat release from the reaction
      of the Frustrated Lewis Pair (FLP) with H(2) as a function of time yields a
      relative rate of hydrogenation in addition to the enthalpy of hydrogenation. The
      half-lives of hydrogenation range from 230 s with TMP, DeltaH(H2) = -31.5(0.2)
      kcal mol(-1), to 1400 s with Lut, DeltaH(H2) = -23.4(0.4) kcal mol(-1). The (11)B
      nuclear magnetic resonance (NMR) spectrum of B(C(6)F(5))(3) in bromobenzene
      exhibits three distinct traits depending on the sterics of the Lewis base; (1) in
      the presence of pyridine, only the dative bond adduct pyridine-B(C(6)F(5))(3) is
      observed; (2) in the presence of TMP and MeTMP, only the free B(C(6)F(5))(3) is
      observed; and (3) in the presence of Lut, both the free B(C(6)F(5))(3) and the
      Lut-B(C(6)F(5))(3) adduct appear in equilibrium. A measure of the change in K(eq)
      of Lut + B(C(6)F(5))(3)    <=> Lut-B(C(6)F(5))(3) as a function of temperature
      provides thermodynamic properties of the Lewis acid Lewis base adduct, DeltaH = 
      17.9(1.0) kcal mol(-1) and a DeltaS = -49.2(2.5) cal mol(-1) K, suggesting the
      Lut-B(C(6)F(5))(3) adduct is more stable in bromobenzene than in toluene.

PMID- 22996637
TI  - Conjugation of transferrin to azide-modified CdSe/ZnS core-shell quantum dots
      using cyclooctyne click chemistry.
AB  - Twinkle twinkle quantum dot: Conjugation of biomolecules to azide-modified
      quantum dots (QDs) through a bifunctional linker, using strain-promoted azide
      alkyne cycloaddition with the QD and a squaramide linkage to the biomolecule (see
      scheme). Transferrin-conjugated QDs were internalized by transferrin-receptor
      expressing HeLa cells.

PMID- 22996638
TI  - Psychosocial correlates of atrial natriuretic peptide: a marker of vascular
      health.
AB  - BACKGROUND: Psychosocial factors have been associated with cardiovascular
      outcomes, but few studies have examined the association between psychosocial
      function and natriuretic peptides. PURPOSE: The purpose of this study is to
      determine the predictive value of hostility, anger, and social support in
      relation to atrial natriuretic peptide (ANP), a marker of vascular health, among
      middle-aged men. METHODS: One hundred twenty-one men (mean age = 39.8 years, SD =
      4.1) underwent assessments of ANP and completed the Cook-Medley Hostility Scale,
      the Spielberger State-Trait Anger Scale, and the Interview Schedule for Social
      Interaction. RESULTS: Higher levels of hostility (beta = 0.22 [95 % CI 0.04,
      0.40], P = 0.032) and trait anger (beta = 0.18 [95 % CI 0.01, 0.37], P = 0.044)
      were associated with greater ANP levels. In contrast, higher perceived social
      support was also associated with lower ANP levels, (beta = -0.19 [95 % CI -0.05, 
      0.41], P = 0.010). CONCLUSIONS: Psychosocial factors, including hostility, anger,
      and social support, are associated with varying ANP levels among middle-aged men,
      independent of cardiovascular and behavioral risk factors.

PMID- 22996639
TI  - Assessment of side effects coping practices of HIV-infected patients receiving
      antiretroviral therapy.
AB  - PURPOSE: The study assessed coping practices to HIV treatment side effects among
      HIV-infected patients receiving antiretroviral therapy (ART) in selected
      hospitals in Nigeria. METHODS: In a cross-sectional study, Side Effects Coping
      (SECope) instrument was administered to 3650 HIV-infected patients receiving ART
      in 36 hospitals. Patients were provided pre-treatment information on side effects
      of antiretroviral drugs. Factor analysis was performed using principal components
      extraction with varimax rotation. Factors selected for rotation had eigenvalues
      >1. Mean scale scores above midpoint of 3.18 on five-point scale were regarded as
      positive coping practices and below as negative practices. Chi-Square was used
      for inferential statistics; P < 0.05 used to determine statistical significance.
      RESULTS: Mean of SECope instrument return rates was 47.5% (95%CI, 37.1-57.9).
      Data from 2329 (63.8%) participants were analyzed: 63.1% females and 63.9% aged
      25 to 44 years old. The mean SECope scale score (+/-SD) was 3.18 (+/-0.80); mean
      subscale scores (+/-SD) were 3.52 (+/-0.20) positive emotion focused coping, 2.82
      (+/-0.18) information seeking, 2.57 (+/-0.30) social support seeking, 2.34 (+/
      0.39) taking side effect medications, and 4.43 (+/-0.10) non-adherence. Five
      extracted factors accounted for 67.2% of cumulative variability. All items had
      very significant loadings of 0.50 or greater. All subscales except positive
      emotion focused coping were associated with age (p < 0.05). Non-adherence and
      information seeking subscales were associated with employment status (p < 0.05).
      Taking side effect medications was associated with educational status (p < 0.05).
      CONCLUSION: The study reported positive coping practices in positive emotion
      focused coping and non-adherence subscales. Non-adherence as a coping strategy
      was not significant contrary to previous research finding.

PMID- 22996640
TI  - Effects of axle-core, macrocycle, and side-station structures on the threading
      and hydrolysis processes of imine-bridged rotaxanes.
AB  - Imine-bridged rotaxanes are a new type of rotaxane in which the axle and
      macrocyclic ring are connected by imine bonds. We have previously reported that
      in imine-bridged rotaxane 5, the shuttling motion of the macrocycle could be
      controlled by changing the temperature. In this study, we investigated how the
      axle and macrocycle structures affect the construction of the imine-bridged
      rotaxane as well as the dynamic equilibrium between imine-bridged rotaxane 5 and
      [2]rotaxane 7 by using various combinations of axles (1 A,B), macrocycles (2 a
      e), and side-stations (XYL and TEG). In the threading process, the flexibility of
      the macrocycle and the substituent groups at the para position of the aniline
      moieties affect the preparation of the threaded imines. The size of the imine
      bridging station and the macrocyclic tether affects the hydrolysis of the imine
      bonds under acidic conditions.

PMID- 22996641
TI  - Reston virus in domestic pigs in China.
AB  - Historically, Reston virus (RESTV) has been found to be associated with outbreaks
      of disease only in nonhuman primates. Its spread to domestic pigs was reported
      for the first time in 2008. In this study, we report the discovery, molecular
      detection, and phylogenetic analysis of Reston virus (RESTV) in domestic pigs in
      China. A total of 137 spleen specimens from pigs that died after showing typical
      clinical signs of porcine reproductive and respiratory syndrome (PRRS), and for
      which infection with porcine reproductive and respiratory syndrome virus (PRRSV)
      was confirmed by RT-PCR, were collected from three farms in Shanghai from
      February to September 2011. Of these samples, 2.92 % (4/137) were found to be
      positive for RESTV. All of the positive piglets were under the age of 8 weeks and
      were co-infected with PRRSV. Sequences were found that shared 96.1 %-98.9 %
      sequence similarity with those of two RESTV variants that had been discovered
      previously in domestic pigs and cynomolgus macaques from the Philippines. We
      therefore conclude that RESTV was present in domestic pigs in Shanghai, China.

PMID- 22996642
TI  - Continuous biodegradation of parathion by immobilized Sphingomonas sp. in
      magnetically fixed-bed bioreactors and evaluation of the enzyme stability of
      immobilized bacteria.
AB  - Magnetically-modified Sphingomonas sp. was prepared using covalent binding of
      magnetic nanoparticles on to the cell surface. The magnetic modified bacteria
      were immobilized in the fixed-bed bioreactors (FBR) by internal and external
      magnetic fields for the biodetoxification of a model organophosphate, parathion:
      93 % of substrate (50 mg parathion/l) was hydrolyzed at 0.5 ml/min in internal
      magnetic field fixed-bed bioreactor. The deactivation rate constants (at 1
      ml/min) were 0.97 * 10(-3), 1.24 * 10(-3) and 4.17 * 10(-3) h(-1) for immobilized
      bacteria in external and internal magnetic field fixed-bed bioreactor and FBR,
      respectively. The deactivation rate constant for immobilized magnetically
      modified bacteria in external magnetic field fixed-bed bioreactor (EMFFBR) was 77
      % lower than that of immobilized cells by entrapping method on porous basalt
      beads in FBR at 1 ml/min. Immobilized magnetic modified bacteria exhibited
      maximum enzyme stability in EMFFBR.

PMID- 22996643
TI  - Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish.
AB  - Mutations in patatin-like phospholipase domain containing 6 (PNPLA6), also known
      as neuropathy target esterase (NTE) or SPG39, cause hereditary spastic paraplegia
      (HSP). Although studies on animal models, including mice and Drosophila, have
      extended our understanding of PNPLA6, its roles in neural development and in HSP
      are not clearly understood. Here, we describe the generation of a vertebrate
      model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in
      zebrafish (Danio rerio). Pnpla6 knockdown resulted in developmental abnormalities
      and motor neuron defects, including axon truncation and branching. The phenotypes
      in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but
      not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP
      signaling in pnpla6 knockdown phenotypes. Taken together, these results
      demonstrate an important role of PNPLA6 in motor neuron development and implicate
      overexpression of BMP signaling as a possible mechanism underlying the
      developmental defects in pnpla6 morphants.

PMID- 22996644
TI  - An intronic ncRNA-dependent regulation of SORL1 expression affecting Abeta
      formation is upregulated in post-mortem Alzheimer's disease brain samples.
AB  - Recent studies indicated that sortilin-related receptor 1 (SORL1) is a risk gene
      for late-onset Alzheimer's disease (AD), although its role in the aetiology
      and/or progression of this disorder is not fully understood. Here, we report the
      finding of a non-coding (nc) RNA (hereafter referred to as 51A) that maps in
      antisense configuration to intron 1 of the SORL1 gene. 51A expression drives a
      splicing shift of SORL1 from the synthesis of the canonical long protein variant
      A to an alternatively spliced protein form. This process, resulting in a
      decreased synthesis of SORL1 variant A, is associated with impaired processing of
      amyloid precursor protein (APP), leading to increased Abeta formation.
      Interestingly, we found that 51A is expressed in human brains, being frequently
      upregulated in cerebral cortices from individuals with Alzheimer's disease.
      Altogether, these findings document a novel ncRNA-dependent regulatory pathway
      that might have relevant implications in neurodegeneration.

PMID- 22996645
TI  - An in vivo large-scale chemical screening platform using Drosophila for anti
      cancer drug discovery.
AB  - Anti-cancer drug development involves enormous expenditure and risk. For rapid
      and economical identification of novel, bioavailable anti-tumour chemicals, the
      use of appropriate in vivo tumour models suitable for large-scale screening is
      key. Using a Drosophila Ras-driven tumour model, we demonstrate that tumour
      overgrowth can be curtailed by feeding larvae with chemicals that have the in
      vivo pharmacokinetics essential for drug development and known efficacy against
      human tumour cells. We then develop an in vivo 96-well plate chemical screening
      platform to carry out large-scale chemical screening with the tumour model. In a
      proof-of-principle pilot screen of 2000 compounds, we identify the glutamine
      analogue, acivicin, a chemical with known activity against human tumour cells, as
      a potent and specific inhibitor of Drosophila tumour formation. RNAi-mediated
      knockdown of candidate acivicin target genes implicates an enzyme involved in
      pyrimidine biosynthesis, CTP synthase, as a possible crucial target of acivicin
      mediated inhibition. Thus, the pilot screen has revealed that Drosophila tumours
      are glutamine-dependent, which is an emerging feature of many human cancers, and
      has validated the platform as a powerful and economical tool for in vivo chemical
      screening. The platform can also be adapted for use with other disease models,
      thus offering widespread applications in drug development.

PMID- 22996646
TI  - Trisomy 13 detection in the first trimester of pregnancy using a chromosome
      selective cell-free DNA analysis method.
AB  - OBJECTIVE: To assess the performance of chromosome-selective sequencing of
      maternal plasma cell-free DNA (cfDNA) in non-invasive prenatal testing for
      trisomy 13. METHODS: Two-phase case-control study on a single plasma sample per
      case. The first phase was used to optimize the trisomy 13 algorithm, which was
      then applied to a second dataset to determine the risk score for trisomy 13 by
      laboratory personnel who were blinded to the fetal karyotype. RESULTS: In the
      first phase, trisomy 13 risk scores were given for 11 cases of trisomy 13 and 145
      euploid cases at 11-13 weeks' gestation. The test identified seven (63.6%) cases
      of trisomy 13 with no false positives. The trisomy 13 algorithm was subsequently
      modified and the trisomy 13 risk score was > 99% in all 11 cases of trisomy 13
      and < 0.01% in all 145 euploid cases. In the second phase, the new algorithm was
      used to generate trisomy 13 risk scores for 10 cases of trisomy 13 and 1939
      euploid cases. The trisomy 13 risk scores were > 99% in eight (80.0% (95%
      confidence interval (CI), 49.0-94.3%)) cases of trisomy 13. In the 1939 euploid
      cases the risk score for trisomy 13 was < 0.01% in 1937 (99.9%), 0.79% in one,
      and > 99% in one. Therefore, at the predefined risk cut-off of 1% for classifying
      a sample as high or low risk, the false-positive rate (FPR) was 0.05% (95% CI,
      0.0-0.3%). CONCLUSIONS: Chromosome-selective sequencing of cfDNA can detect the
      majority of cases of trisomy 13 at an FPR of less than 0.1%.

PMID- 22996647
TI  - Dystroglycan function is a novel determinant of tumor growth and behavior in
      prostate cancer.
AB  - BACKGROUND: Dystroglycan is a ubiquitously expressed cell adhesion molecule
      frequently found to be altered or reduced in adenocarcinomas, however the
      mechanisms or consequences of dystroglycan loss have not been studied
      extensively. METHODS: We examined the consequence of overexpression or RNAi
      depletion of dystroglycan on properties of in vitro growth migration and invasion
      of LNCaP, PC3, and DU145 prostate cancer cell lines. RESULTS: Using LNCaP cells
      we observed cell density-dependent changes in beta-dystroglycan with the
      appearance of several lower molecular weight species ranging in size from 43 to
      26 kDa. The bands of 31 and 26 kDa were attributed to proteolysis, whereas bands
      between 43 and 38 kDa were a consequence of mis-glycosylation. The localization
      of beta-dystroglycan in LNCaP colonies in culture also varied, cells with a
      mesenchymal appearance at the periphery of the colony had more pronounced
      membrane localization of dystroglycan. Whereas some cells demonstrated nuclear
      dystroglycan. Increased dystroglycan levels were inhibitory to growth in soft
      agar but promoted Matrigel invasion, whereas reduced dystroglycan levels promoted
      growth in soft agar but inhibited invasion. Similar results were also obtained
      for PC3 and DU145 cells. CONCLUSIONS: This study suggests that changes in beta
      dystroglycan distribution within the cell and/or the loss of dystroglycan during
      tumorigenesis, through a combination of proteolysis and altered glycosylation,
      leads to an increased ability to grow in an anchorage independent manner, however
      dystroglycan may need to be re-expressed for cell invasion and metastasis to
      occur.

PMID- 22996648
TI  - Health-related quality of life in the aftermath of child maltreatment: follow-up
      study of a hospital sample.
AB  - OBJECTIVE: In the aftermath of child maltreatment or neglect, the health-related
      quality of life (HRQoL) in children is likely to be affected. However, research
      on quality of life in maltreated children is lacking. The aim of this study is to
      compare the HRQoL in a follow-up sample of children referred to an
      interdisciplinary hospital child protection team (CPT) to match controls and to
      explore correlates of HRQoL. METHOD: Of the 319 in- and outpatient children
      referred to the CPT at the University Children's Hospital Zurich between 2005 and
      2006, an eligible sample of 180 children was contacted for a follow-up. HRQoL was
      assessed for 42 former patients using the self- and proxy-rated KIDSCREEN-27 for
      children above the age of 6 years and the TAPQOL parent report for children
      younger than 6 years. HRQoL-scores in the maltreatment group were compared with
      HRQoL in 39 matched controls. RESULTS: Self-reported HRQoL in maltreated children
      above the age of 6 years was significantly impaired compared to matched controls.
      The caregiver-rated HRQoL of maltreated children, however, was not affected. Low
      socioeconomic status and number of life events were associated with impaired self
      reported HRQoL. Analyzed together with these factors, maltreatment lost its
      predictive power on HRQoL. CONCLUSION: Maltreated children and adolescents suffer
      from impaired HRQoL even after the maltreatment has been disclosed and targeted
      by interventions. The impact of socioeconomic environment reinforces the
      importance of a multidisciplinary and systemic approach to maltreatment as
      applied by the CPT. Although the nature of discordance between child and
      caregiver report is not known, researchers and clinicians are strongly encouraged
      to assess the victim's self-reported HRQoL independently of their proxies' view.

PMID- 22996649
TI  - Studies on the fate of ready-mix formulation of endosulfan and cypermethrin in
      tea.
AB  - Ready-mix formulation consists of two insecticides-endosulfan (35%) and
      cypermethrin (5%). To understand the dissipation pattern of the insecticides on
      made tea from the north-east region of India, it was applied twice in 10 day
      interval @ 1,000 mL/ha (350 g a.i. endosulfan + 50 g a.i. cypermethrin) and 2,000
      mL/ha (700 g a.i. endosulfan + 100 g a.i. cypermethrin) along with untreated
      control. The made tea samples were collected at 0, 1, 3 and 7 days interval after
      last application. The dissipation rate of endosulfan and cypermethrin followed
      first order kinetics. The calculated half-life values were found in the range
      between 1.7 to 2.1 days for endosulfan and 1.0 to 1.1 days for cypermethrin.

PMID- 22996650
TI  - Multiresidue determination of organophorous pesticides in camellia oil by matrix
      solid-phase dispersion followed by GC-FPD.
AB  - A novel analytical approach has been developed and evaluated for the quantitative
      analysis of 15 organophorous pesticides residues in camellia oils. The proposed
      methodology is based on acetonitrile/water (3:1, V/V) extraction, followed by
      matrix solid-phase dispersion, using aminopropyl as dispersant material. Then gas
      chromatography-flame photometric detection was applied for the pesticide residue
      analysis. The optimal sorbent quantity was studied. The results demonstrated that
      the method achieved acceptable quantitative recoveries of 71.5%-104.2% with
      relative standard deviations <19%, and the method limit of detection at or below
      the regulatory maximum residue limits for the pesticides were achieved.

PMID- 22996651
TI  - Hexavalent chromium contamination in groundwaters of Thiva Basin, central Greece.
AB  - There is an increasing concern regarding elevated levels of Cr(VI) in the
      environment due to its higher mobility and toxicity compared to the trivalent
      form. Anomalous hexavalent chromium concentrations (up to 212 MUg/L) were
      determined in irrigated groundwaters from the wider area of Thiva Basin (central
      Greece), frequently exceeding the permissible limit for human consumption (50
      MUg/L for total Cr). Based on the spatial distribution of Cr(VI) values, two
      groups of groundwater samples were distinguished, possibly reflecting different
      natural and/or anthropogenic factors that govern the levels of contamination. The
      first group is spatially located northwards of Thiva town and is consisted of
      concentrations that range from 13 to 212 MUg/L (median 58 MUg/L), while the
      second group is located near Mouriki village and Cr(VI) values range from <9 to
      14 MUg/L. The Cr(VI) chemical anomalies represent an important social problem
      because the agricultural products of this region are a major vegetable supply for
      Greece, bringing up the urgent need to evaluate the health effects associated
      with Cr(VI) exposure by ingesting the potentially contaminated foods.

PMID- 22996652
TI  - Organochlorine pesticides in green mussel, Perna viridis, from the Cienfuegos
      Bay, Cuba.
AB  - The green mussel, Perna viridis, was used to measure bioaccumulated levels of
      organochlorine pesticides in the marine environment of Cuba. Samples were
      collected in the Cienfuegos Bay between January and December 2010. The
      organochlorine pesticides (i.e. DDT, Dieldrin, Chlordane, Endosulfan, HCB,
      Aldrin, Heptachlor and Lindane) were quantified by gas chromatography. The sum of
      all organochlorine pesticides in P. viridis was 6.31 ng g(-1). The concentration
      ranged from 3.53 to 4.42 ng g(-1) dry weight (dw) for DDTs (i.e. sum of pp' DDT,
      pp' DDD, op' DDE and pp' DDE); 1.7-1.9 ng g(-1) dw for Dieldrin; 0.17-0.20 ng g(
      1) dw for Chlordanes; 0.14-0.16 ng g(-1) dw for Endosulfan; 0.11-0.17 ng g(-1) dw
      for HCB; 0.07-0.11 ng g(-1) dw for Aldrin; 0.046-0.054 ng g(-1) dw for Heptachlor
      and 0.035-0.039 ng g(-1) dw for Lindane. These levels can be considered as low
      when compared to reported values from similar studies conducted elsewhere in the
      world. The concentrations of all organochlorines residues detected in this study
      fell below the EU Maximum Residue Limits.

PMID- 22996653
TI  - MYC addiction: a potential therapeutic target in MM.
AB  - In this issue of Blood, Holien et al report that MYC addiction is responsible for
      rapid death of myeloma cell lines and primary myeloma tumor cells treated with a
      specific MYC inhibitor.

PMID- 22996654
TI  - Stubborn Tregs limit T-cell therapy.
AB  - In this issue of Blood, Baba and colleagues characterize a residual pool
      ofCD4+CD25+Foxp3+ regulatory T cells (Tregs) surviving a nonmyeloablative
      conditioning regimen that undergo robust homeostatic expansion to limit the full
      potential of adoptive T-cell therapy (ACT) for the treatment of cancer.

PMID- 22996655
TI  - Cp-jeez! Aza-natomy!
AB  - In this issue of Blood, Yan et al study the anatomy of azanuceoside methylation
      reversal.

PMID- 22996656
TI  - SNARing platelet granule secretion.
AB  - In this issue of Blood, Ye et al and Al Hawas et al clarify the roles of 2 key
      fusion proteins that regulate the agonist-stimulated release of bioactive factors
      from platelets, and thereby explain the defective hemostasis in patients with 2
      rare genetic diseases.

PMID- 22996657
TI  - AML cytogenetics: the complex just got simpler.
AB  - In this issue of Blood, Middeke et al, for the well-regarded Cooperative German
      Study Group, report a retrospective analysis in which they demonstrate that a
      hierarchial classification system for specific cytogenetic abnormalities in acute
      myeloid leukemia (AML) reveals that patients with abnormal 17p [abnl(17p)] and 
      5/5q- abnormalities have worse outcomes after allogeneic hematopoietic cell
      transplantation (HCT).

PMID- 22996658
TI  - Contribution of bone marrow-derived endothelial progenitor cells to
      neovascularization and astrogliosis following spinal cord injury.
AB  - Spinal cord injury causes initial mechanical damage, followed by ischemia
      induced, secondary degeneration, worsening the tissue damage. Although
      endothelial progenitor cells (EPCs) have been reported to play an important role
      for pathophysiological neovascularization in various ischemic tissues, the EPC
      kinetics following spinal cord injury have never been elucidated. In this study,
      we therefore assessed the in vivo kinetics of bone marrow-derived EPCs by EPC
      colony-forming assay and bone marrow transplantation from Tie2/lacZ transgenic
      mice into wild-type mice with spinal cord injury. The number of circulating
      mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day
      3 postspinal cord injury. Bone marrow transplantation study revealed that bone
      marrow-derived EPCs recruited into the injured spinal cord markedly increased at
      day 7, when neovascularization and astrogliosis drastically occurred in parallel
      with axon growth in the damaged tissue. To elucidate further the contribution of
      EPCs to recovery after spinal cord injury, exogenous EPCs were systemically
      infused immediately after the injury. The administered EPCs were incorporated
      into the injured spinal cord and accelerated neovascularization and astrogliosis.
      These findings suggest that bone marrow-derived EPCs may contribute to the tissue
      repair by augmenting neovascularization and astrogliosis following spinal cord
      injury.

PMID- 22996659
TI  - Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and
      vascular integrity.
AB  - Haploinsufficiency for GATA2 causes human immunodeficiency syndromes
      characterized by mycobacterial infection, myelodysplasia, lymphedema, or aplastic
      anemia that progress to myeloid leukemia. GATA2 encodes a master regulator of
      hematopoiesis that is also linked to endothelial biology. Though the disease
      causing mutations commonly occur in the GATA-2 DNA binding domain, we identified
      a patient with mycobacterial infection and myelodysplasia who had an
      uncharacterized heterozygous deletion in a GATA2 cis-element consisting of an E
      box and a GATA motif. Targeted deletion of the equivalent murine element to yield
      homozygous mutant mice revealed embryonic lethality later than occurred with
      global Gata2 knockout, hematopoietic stem/progenitor cell depletion, and impaired
      vascular integrity. Heterozygous mutant mice were viable, but embryos exhibited
      deficits in definitive, but not primitive, hematopoietic stem/progenitor activity
      and reduced expression of Gata2 and its target genes. Mechanistic analysis
      revealed disruption of the endothelial cell transcriptome and loss of vascular
      integrity. Thus, the composite element disrupted in a human immunodeficiency is
      essential for establishment of the murine hematopoietic stem/progenitor cell
      compartment in the fetal liver and for essential vascular processes.

PMID- 22996660
TI  - Adipocyte iron regulates adiponectin and insulin sensitivity.
AB  - Iron overload is associated with increased diabetes risk. We therefore
      investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine
      that is decreased in diabetic patients. In humans, normal-range serum ferritin
      levels were inversely associated with adiponectin, independent of inflammation.
      Ferritin was increased and adiponectin was decreased in type 2 diabetic and in
      obese diabetic subjects compared with those in equally obese individuals without
      metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated
      with iron exhibited decreased adiponectin mRNA and protein. We found that iron
      negatively regulated adiponectin transcription via FOXO1-mediated repression.
      Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted
      in adipocyte iron loading, decreased adiponectin, and insulin resistance.
      Conversely, organismal iron overload and increased adipocyte ferroportin
      expression because of hemochromatosis are associated with decreased adipocyte
      iron, increased adiponectin, improved glucose tolerance, and increased insulin
      sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin
      values in the highest quartile of normal increased adiponectin and improved
      glucose tolerance. These findings demonstrate a causal role for iron as a risk
      factor for metabolic syndrome and a role for adipocytes in modulating metabolism
      through adiponectin in response to iron stores.

PMID- 22996661
TI  - NR4A nuclear receptors support memory enhancement by histone deacetylase
      inhibitors.
AB  - The formation of a long-lasting memory requires a transcription-dependent
      consolidation period that converts a short-term memory into a long-term memory.
      Nuclear receptors compose a class of transcription factors that regulate diverse
      biological processes, and several nuclear receptors have been implicated in
      memory formation. Here, we examined the potential contribution of nuclear
      receptors to memory consolidation by measuring the expression of all 49 murine
      nuclear receptors after learning. We identified 13 nuclear receptors with
      increased expression after learning, including all 3 members of the Nr4a
      subfamily. These CREB-regulated Nr4a genes encode ligand-independent "orphan"
      nuclear receptors. We found that blocking NR4A activity in memory-supporting
      brain regions impaired long-term memory but did not impact short-term memory in
      mice. Further, expression of Nr4a genes increased following the memory-enhancing
      effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling
      interfered with the ability of HDAC inhibitors to enhance memory. These results
      demonstrate that the Nr4a gene family contributes to memory formation and is a
      promising target for improving cognitive function.

PMID- 22996662
TI  - Alveolar epithelial cells orchestrate DC function in murine viral pneumonia.
AB  - Influenza viruses (IVs) cause pneumonia in humans with progression to lung
      failure. Pulmonary DCs are key players in the antiviral immune response, which is
      crucial to restore alveolar barrier function. The mechanisms of expansion and
      activation of pulmonary DC populations in lung infection remain widely elusive.
      Using mouse BM chimeric and cell-specific depletion approaches, we demonstrated
      that alveolar epithelial cell (AEC) GM-CSF mediates recovery from IV-induced
      injury by affecting lung DC function. Epithelial GM-CSF induced the recruitment
      of CD11b+ and monocyte-derived DCs. GM-CSF was also required for the presence of
      CD103+ DCs in the lung parenchyma at baseline and for their sufficient activation
      and migration to the draining mediastinal lymph nodes (MLNs) during IV infection.
      These activated CD103+ DCs were indispensable for sufficient clearance of IVs by
      CD8+ T cells and for recovery from IV-induced lung injury. Moreover, GM-CSF
      applied intratracheally activated CD103+ DCs, inducing increased migration to
      MLNs, enhanced viral clearance, and attenuated lung injury. Together, our data
      reveal that GM-CSF-dependent cross-talk between IV-infected AECs and CD103+ DCs
      is crucial for effective viral clearance and recovery from injury, which has
      potential implications for GM-CSF treatment in severe IV pneumonia.

PMID- 22996663
TI  - MicroRNAs contribute to compensatory beta cell expansion during pregnancy and
      obesity.
AB  - Pregnancy and obesity are frequently associated with diminished insulin
      sensitivity, which is normally compensated for by an expansion of the functional
      beta cell mass that prevents chronic hyperglycemia and development of diabetes
      mellitus. The molecular basis underlying compensatory beta cell mass expansion is
      largely unknown. We found in rodents that beta cell mass expansion during
      pregnancy and obesity is associated with changes in the expression of several
      islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we
      recapitulated the decreased miR-338-3p level observed in gestation and obesity by
      activating the G protein-coupled estrogen receptor GPR30 and the glucagon-like
      peptide 1 (GLP1) receptor. Blockade of miR-338-3p in beta cells using specific
      anti-miR molecules mimicked gene expression changes occurring during beta cell
      mass expansion and resulted in increased proliferation and improved survival both
      in vitro and in vivo. These findings point to a major role for miR-338-3p in
      compensatory beta cell mass expansion occurring under different insulin
      resistance states.

PMID- 22996664
TI  - Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.
AB  - Plasmodium falciparum, which causes the most lethal form of human malaria,
      replicates in the host liver during the initial stage of infection. However, in
      vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in
      vitro models of LS development do not reconstitute relevant parasite growth
      conditions. To overcome these obstacles, we have adopted a robust mouse model for
      the study of P. falciparum LS in vivo: the immunocompromised and
      fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed
      the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice
      supported vigorous, quantifiable P. falciparum LS development that culminated in
      complete maturation of LS at approximately 7 days after infection, providing a
      relevant model for LS development in humans. The infections allowed observations
      of previously unknown expression of proteins in LS, including P. falciparum
      translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2),
      components of a known parasite protein export machinery. LS schizonts exhibited
      exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice
      backcrossed to the NOD background and repopulated with huHeps and human red blood
      cells supported reproducible transition from LS infection to blood-stage
      infection. Thus, these mice constitute reliable models to study human LS directly
      in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a
      human malaria parasite.

PMID- 22996665
TI  - Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning.
AB  - The transcription factor GATA-2 plays vital roles in quite diverse developmental
      programs, including hematopoietic stem cell (HSC) survival and proliferation. We
      previously identified a vascular endothelial (VE) enhancer that regulates GATA-2
      activity in pan-endothelial cells. To more thoroughly define the in vivo
      regulatory properties of this enhancer, we generated a tamoxifen-inducible Cre
      transgenic mouse line using the Gata2 VE enhancer (Gata2 VECre) and utilized it
      to temporally direct tissue-specific conditional loss of Gata2. Here, we report
      that Gata2 VECre-mediated loss of GATA-2 led to anemia, hemorrhage, and eventual
      death in edematous embryos. We further determined that the etiology of anemia in
      conditional Gata2 mutant embryos involved HSC loss in the fetal liver, as
      demonstrated by in vitro colony-forming and immunophenotypic as well as in vivo
      long-term competitive repopulation experiments. We further documented that the
      edema and hemorrhage in conditional Gata2 mutant embryos were due to defective
      lymphatic development. Thus, we unexpectedly discovered that in addition to its
      contribution to endothelial cell development, the VE enhancer also regulates GATA
      2 expression in definitive fetal liver and adult BM HSCs, and that GATA-2
      function is required for proper lymphatic vascular development during
      embryogenesis.

PMID- 22996667
TI  - Catalysts for suzuki polycondensation: ionic and "quasi-ionic" amphipathic
      palladium complexes with self-phase-transfer features.
AB  - Poly(9,9-dioctylfluorene) (PFO) with M(n) values above 100,000 g mol(-1) in a
      toluene/water system and M(n) values up to 600,000 g mol(-1) in a THF/water
      system has been obtained by improved Suzuki polycondensation using a new kind of
      amphipathic palladium catalyst with self-phase-transfer features, which could
      overcome the disadvantage caused by the immiscible biphasic mixture and
      accelerate the transmetalation step.

PMID- 22996666
TI  - Novel covalently coated diazoresin/polyvinyl alcohol capillary column for the
      analysis of proteins by capillary electrophoresis.
AB  - A novel method for the preparation of covalently linked capillary coatings of PVA
      was demonstrated using photosensitive diazoresin (DR) as coupling agents. Layer
      by-layer self-assembly film of DR and PVA based on hydrogen bonding was first
      fabricated on the inner wall of capillary, then the hydrogen bonding was
      converted into covalent bonding after treatment with UV light through the unique
      photochemistry reaction of DR. The covalently bonded coatings suppressed basic
      protein adsorption on the inner surface of capillary, and thus a baseline
      separation of lysozyme, cytochrome c and BSA was achieved using CE. Compared with
      bare capillary or noncovalently bonded DR/PVA coatings, the covalently linked
      DR/PVA capillary coatings not only improved the CE separation performance for
      proteins, but also exhibited good stability and repeatability. Due to the
      replacement of highly toxic and moisture-sensitive silane coupling agent by DR in
      the covalent coating preparation, this method may provide a green and easy way to
      make the covalently coated capillaries for CE.

PMID- 22996668
TI  - Endolymphatic space imaging in idiopathic sudden sensorineural hearing loss with
      vertigo.
AB  - OBJECTIVES/HYPOTHESIS: To investigate endolymphatic space images in patients with
      idiopathic sudden sensorineural hearing loss (ISNHL) and vertigo using three
      dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D
      FLAIR MRI). STUDY DESIGN: This is a prospective study of an analysis using the
      imaging technology of 3D-FLAIR MRI for patients with ISNHL and vertigo. METHODS:
      3D-FLAIR MRI was performed 24 hours after intratympanic injection of gadolinium
      diethylenetriamine penta-acetic acid. RESULTS: In four of seven cases of ISNHL
      with vertigo, endolymphatic hydrops were confirmed in the cochlea and/or the
      vestibule of the affected ears. CONCLUSIONS: The results of the study imply that
      there may be some relationship between endolymphatic hydrops and ISNHL with
      vertigo.

PMID- 22996671
TI  - A feasibility study on pellet coating using a high-speed quasi-continuous coater.
AB  - Pellet coating is traditionally carried out using the Wurster coater. This study
      investigated the feasibility of pellet coating in a newly developed coater built
      with a unique airflow system, the SupercellTM coater (GEA Pharma Systems, UK). A
      full factorial design study was carried out to evaluate the influences of the
      spray rate of the coating dispersion, batch size of the pellet load, pellet size
      fraction and plenum pressure of the fluidizing air on the color coating of
      pellets in the SupercellTM coater. Results showed that pellets could be
      successfully coated using the SupercellTM coater. Higher plenum pressures and
      lower spray rates were found to minimize pellet agglomeration during coating.
      Although coating efficiencies were comparable amongst the different pellet size
      fractions, larger batch sizes of pellets were coated with higher efficiencies.
      Process optimization was carried out for each pellet size fraction and a large
      batch size (120 g) in combination with a high plenum pressure (1,500 mm WC) were
      deemed optimal. Optimal spray rates differed according to pellet size fraction
      and a lower spray rate was required for smaller pellets. Pellet flow patterns
      observed during coating were dependent on the pressure drop across the fluidized
      load. A 'swirling' pellet flow pattern was generally observed at coating
      conditions which led to optimal outcomes.

PMID- 22996670
TI  - Microemulsion-based oxyresveratrol for topical treatment of herpes simplex virus
      (HSV) infection: physicochemical properties and efficacy in cutaneous HSV-1
      infection in mice.
AB  - The physicochemical properties of the optimized microemulsion and the permeating
      ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of
      oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1)
      infection in mice was examined. The optimized microemulsion was composed of 10%
      w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol,
      and 20% w/w of water. The mean particle diameter was 9.67 +/- 0.58 nm, and the
      solubility of oxyresveratrol in the microemulsion was 196.34 +/- 0.80 mg/ml.
      After accelerated and long-term stability testing, the microemulsion base and
      oxyresveratrol-loaded microemulsion were stable. The cumulative amount of
      oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was
      93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20%
      w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol
      microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7
      days after infection, was significantly effective in delaying the development of
      skin lesions and protecting from death (p < 0.05) compared with the untreated
      control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more
      effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was
      as effective as 5% w/w of acyclovir cream, topically applied five times daily (p
      > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at
      20-30% w/w was suitable for cutaneous HSV-1 mouse infection.

PMID- 22996672
TI  - Development of a continuous dissolution/absorption system--a technical note.

PMID- 22996673
TI  - The use of artificial neural networks for optimizing polydispersity index (PDI)
      in nanoprecipitation process of acetaminophen in microfluidic devices.
AB  - Artificial neural networks (ANNs) were used in this study to determine factors
      that control the polydispersity index (PDI) in an acetaminophen nanosuspension
      which was prepared using nanoprecipitation in microfluidic devices. The PDI of
      prepared formulations was measured by dynamic light scattering. Afterwards, the
      ANNs were applied to model the data. Four independent variables, namely,
      surfactant concentration, solvent temperature, and flow rate of solvent and
      antisolvent were considered as input variables, and the PDI of acetaminophen
      nanosuspension was taken as the output variable. The response surfaces, generated
      as 3D graphs after modeling, were used to survey the interactions happening
      between the input variables and the output variable. Comparison of the response
      surfaces indicated that the antisolvent flow rate and the solvent temperature
      have reverse effect on the PDI, whereas solvent flow rate has direct relation
      with PDI. Also, the effect of the concentration of the surfactant on the PDI was
      found to be indirect and less influential. Overall, it was found that minimum PDI
      may be obtained at high values of antisolvent flow rate and solvent temperature,
      while the solvent flow rate should be kept to a minimum.

PMID- 22996674
TI  - Neurodegeneration, beta-amyloid and mood disorders: state of the art and future
      perspectives.
AB  - OBJECTIVE: Depression may increase the risk of developing Alzheimer's disease
      (AD). Recent studies have shown modifications in blood beta-amyloid (Abeta)
      levels in depressed patients. This literature review examines the potential
      relationship between Abeta-mediated neurotoxicity and pathophysiology of mood
      disorders. DESIGN: We conducted a review of the literature focusing on recent
      studies reporting alterations of plasma and serum Abeta peptides levels in
      patients suffering from mood disorders. RESULTS: Different data suggest that
      patients with mood disorders are at great risk of developing cognitive impairment
      and dementia. In particular, low plasma levels of Abeta42 peptide and a high
      Abeta40/Abeta42 ratio have been found in depressed patients. In addition, changes
      in Abeta protein levels in patients with mood disorders have been associated with
      the severity of cognitive impairment and correlated positively with the number of
      episodes and severity of illness course. CONCLUSIONS: Given the intriguing
      association between change in plasma level of Abeta, depression and cognitive
      impairment, future work should focus on the relationship between Abeta peripheral
      level(s), biomarkers of neurodegeneration and development of dementia in patients
      affected by mood disorders.

PMID- 22996675
TI  - Sugarcane for water-limited environments. Genetic variation in cane yield and
      sugar content in response to water stress.
AB  - Water limitation is a major production constraint for sugarcane worldwide.
      However, to date, there has been little  investigation of patterns of genetic
      variation in the response to water stress in sugarcane. Field experiments were
      conducted over 3 years under fully irrigated and managed water stress conditions
      at two locations in Northern Queensland in Australia. Eighty-nine genetically
      diverse clones were evaluated for their yield performance and sugar attributes.
      Water stress treatments reduced cane yield [tonnes of cane per hectare (TCH)] and
      total dry matter (TDM) by 17-52% and 20-56%, respectively, compared with
      irrigated treatments in the same experiments. Nevertheless, there was little
      genotype*environment interaction variation for TCH, TDM, or commercial cane sugar
      (CCS), and hence high genetic correlations between the irrigated and water stress
      treatments across environments. Both commercial and unselected clones performed
      poorly under severe stress environments, while the commercial clones outperformed
      the unselected clones under mild and moderate stress conditions. The results
      presented here highlight the contribution of intrinsic potential yields (yield
      under well-irrigated conditions) of some selected and unselected clones to
      maintain relatively high productivity in a range of moderate stress conditions
      imposed. The physiological basis for the high genetic correlations is at present
      unclear, but some explanations are hypothesized. The choice of stress levels in
      selection trials would not appear to be a critical issue for sugarcane breeding
      programmes, at least for the early phases of selection, where similar ranking
      clones across a range of moderate water stresses may be expected.

PMID- 22996676
TI  - Photorespiratory bypasses: how can they work?
AB  - Photorespiration has been suggested as a target for increasing photosynthesis for
      decades. Within the last few years, three bypass pathways or reactions have been
      designed and tested in plants. The three reactions bypass photorespiration either
      in the chloroplast or in the peroxisome, or oxidize glycolate completely to CO(2)
      in the chloroplast. The reactions differ in their demand for energy and reducing
      power as well as in the catabolic fate of glycolate. The design, energy balance,
      and reported benefits of the three bypasses are compared here, and an outlook on
      further optimization is given.

PMID- 22996677
TI  - Functional analysis of OsHSBP1 and OsHSBP2 revealed their involvement in the heat
      shock response in rice (Oryza sativa L.).
AB  - The heat shock response (HSR) induces the production of heat shock proteins
      (HSPs) through the activation of heat shock factors (HSF). HSF binding protein
      (HSBP) is reported to modulate the function of HSF by binding to their trimer and
      hence to regulate HSR. This report describes the role of OsHSBP1 and OsHSBP2 in
      the regulation of the HSR and seed development of rice. Both genes expressed
      ubiquitously in all tissues under normal growth conditions while their expression
      levels were significantly increased during recovery after heat shock treatment.
      Subcellular localization revealed the cytosol-nuclear localization of both
      OsHSBP1 and OsHSBP2 in onion epidermal cells. The yeast two-hybrid assay depicted
      the self-binding ability of both genes. Both genes were also important for seed
      development, as their knock-down lines were associated with significant seed
      abortion. The thermotolerance assay revealed that OsHSBP1 and OsHSBP2 are
      negative regulators of HSR and involved in acquired thermotolerance but not in
      basal thermotolerance since their over-expression transgenic lines pre-heated at
      sublethal temperature, showed significantly decreased seedling survival after
      heat shock treatment. Furthermore, antioxidant activity and gene expression of
      catalase and peroxidase was significantly increased in knock-down transgenic
      seedlings of OsHSBP1 and OsHSBP2 after heat stress compared with the wild type.
      The expression of heat specific HSPs was also increased significantly in
      knockdown line of both genes but in a specific manner, suggesting the involvement
      of HSBP genes in different pathways. Overall, the present study reveals the role
      of OsHSBP1 and OsHSBP2 in the regulation of the HSR and seed development of rice.

PMID- 22996678
TI  - Down-regulation of the TaGW2 gene by RNA interference results in decreased grain
      size and weight in wheat.
AB  - For important food crops such as wheat and rice, grain yield depends on grain
      number and size. In rice (Oryza sativa), GW2 was isolated from a major
      quantitative trait locus for yield and encodes an E3 RING ligase that negatively
      regulates grain size. Wheat (Triticum aestivum) has TaGW2 homologues in the A, B,
      and D genomes, and polymorphisms in TaGW2-A were associated with grain width.
      Here, to investigate TaGW2 function, RNA interference (RNAi) was used to down
      regulate TaGW2 transcript levels. Transgenic wheat lines showed significantly
      decreased grain size-related dimensions compared with controls. Furthermore,
      TaGW2 knockdown also caused a significant reduction in endosperm cell number.
      These results indicate that TaGW2 regulates grain size in wheat, possibly by
      controlling endosperm cell number. Wheat and rice GW2 genes thus seem to have
      divergent functions, with rice GW2 negatively regulating grain size and TaGW2
      positively regulating grain size. Analysis of transcription of TaGW2 homoeologues
      in developing grains suggested that TaGW2-A and -D act in both the division and
      late grain-filling phases. Furthermore, biochemical and molecular analyses
      revealed that TaGW2-A is a functional E3 RING ubiquitin ligase with
      nucleocytoplasmic subcellular partitioning. A functional nuclear export sequence
      responsible for TaGW2-A export from the nucleus to the cytosol and retention in
      the nucleolus was identified. Therefore, these results show that TaGW2 acts in
      the regulation of grain size and may provide an important tool for enhancement of
      grain yield.

PMID- 22996679
TI  - Beyond directing groups: transition-metal-catalyzed C-H activation of simple
      arenes.
AB  - The use of coordinating moieties as directing groups for the functionalization of
      aromatic C-H bonds has become an established tool to enhance reactivity and
      induce regioselectivity. Nevertheless, with regard to the synthetic applicability
      of C-H activation, there is a growing interest in transformations in which the
      directing group can be fully abandoned, thus allowing the direct
      functionalization of simple benzene derivatives. However, this approach requires
      the disclosure of new strategies to achieve reactivity and to control
      selectivity. In this review, recent advances in the emerging field of non-chelate
      assisted C-H activation are discussed, highlighting some of the most intriguing
      and inspiring examples of induction of reactivity and selectivity.

PMID- 22996680
TI  - Nurses' recognition of the mental state of cancer patients and their own stress
      management - a study of Japanese cancer-care nurses.
AB  - OBJECTIVE: The primary aim of this study was to describe Japanese oncology
      nurses' self-reported ability to assess and care for cancer patients' mental
      health. A secondary aim was to describe nurses' self-reported stress levels and
      need for stress management related to caring for oncology patients. METHODS: This
      cross-sectional questionnaire study was conducted from September to November 2010
      among cancer-care nurses participating in mental healthcare training. The
      questionnaire asked about assessment of patient anxiety, depression, delirium,
      anger, and acceptance, and included four statements about work-related stress. A
      4-point Likert scale was used for responses. RESULTS: The 88 participants (86
      women) ranged in age from the 20s to the 50s, with the greatest number in their
      30s (47.2%, n=42). More than 50% of nurses were very concerned about assessing
      cancer patient anxiety and depression; approximately 20% were extremely concerned
      about caring for depression and anger in patients. Overall, 83.2% (n=74) of
      cancer-care nurses felt distressed over their occupation, only 19.1% (n=17)
      stated that they were controlling their stress, and over half indicated a need
      for stress-management programs. CONCLUSIONS: Nurses perceived that assessments of
      and care for the mental state of cancer patients were inadequate. Cancer-care
      nurses need training in assessing and caring for the mental state of cancer
      patients, as well as stress management training programs for themselves.

PMID- 22996681
TI  - Nickel complexes with "click"-derived pyridyl-triazole ligands: weak
      intermolecular interactions and catalytic ethylene oligomerisation.
AB  - The ligands 1-(cyclohexyl)-4-(2-pyridyl)-1,2,3-triazole (1), 1-(2,6
      diisopropylphenyl)-4-(2-pyridyl)-1,2,3-triazole (2), 1-(4-butoxyphenyl)-4-(2
      pyridyl)-1,2,3-triazole (3) and 1-(methyl)-4-(2-pyridyl)-1,2,3-triazole (4) were
      synthesized by the Cu(I) catalyzed "Click" reaction between 2-pyridylacetylene
      and the corresponding azides. The ligands were then reacted with NiBr(2).3H(2)O
      to generate the complexes (1)(2)NiBr(2) (1a), (2)(2)NiBr(2) (2a), (3)(2)NiBr(2)
      (3a) and (4)(2)NiBr(2) (4a). Structural characterization of 1a confirmed the
      mononuclear and distorted octahedral environment around the Ni(II) center, with
      the pyridyl-triazole ligands coordinating in a bis-chelating fashion. Bond length
      analysis inside the 1,2,3-triazole ring shows a short N=N double bond that is
      flanked by two longer C-N and N-N bonds pointing to the existence of "azo"
      character in the ring. The highly polar five-membered 1,2,3-triazole ring makes
      its C-H bond acidic, and these bonds participate in an extended weak
      intermolecular C-H...Br interactions with the Br-groups of neighboring molecules,
      resulting in a 3-D network. The nickel complexes with these "Click" ligands were
      tested as pre-catalysts for ethylene oligomerization, and the complexes showed
      moderate activity in that reaction with good selectivity towards C4 oligomers.

PMID- 22996683
TI  - Deficiency in Bim, Bid and Bbc3 (Puma) do not prevent axonal injury induced
      death.

PMID- 22996682
TI  - Multifaceted roles of PGE2 in inflammation and cancer.
AB  - Prostaglandin E(2) (PGE(2)) is a bioactive lipid that elicits a wide range of
      biological effects associated with inflammation and cancer. PGE(2) exerts diverse
      effects on cell proliferation, apoptosis, angiogenesis, inflammation, and immune
      surveillance. This review concentrates primarily on gastrointestinal cancers,
      where the actions of PGE(2) are most prominent, most likely due to the constant
      exposure to dietary and environmental insults and the intrinsic role of PGE(2) in
      tissue homeostasis. A discussion of recent efforts to elucidate the complex and
      interconnected pathways that link PGE(2) signaling with inflammation and cancer
      is provided, supported by the abundant literature showing a protective effect of
      NSAIDs and the therapeutic efficacy of targeting mPGES-1 or EP receptors for
      cancer prevention. However, suppressing PGE(2) formation as a means of providing
      chemoprotection against all cancers may not ultimately be tenable, undoubtedly
      the situation for patients with inflammatory bowel disease. Future studies to
      fully understand the complex role of PGE(2) in both inflammation and cancer will
      be required to develop novel strategies for cancer prevention that are both
      effective and safe.

PMID- 22996684
TI  - p53 counteracts reprogramming by inhibiting mesenchymal-to-epithelial transition.
AB  - The process of somatic cell reprogramming is gaining increasing interest as
      reprogrammed cells are considered to hold a great therapeutic potential. However,
      with current technologies this process is relatively inefficient. Recent studies
      reported that inhibition of the p53 tumor suppressor profoundly facilitates
      reprogramming and attributed this effect to the ability of p53 to restrict
      proliferation and induce apoptosis. Given that mesenchymal-to-epithelial
      transition (MET) was recently shown to be necessary for reprogramming of
      fibroblasts, we investigated whether p53 counteracts reprogramming by affecting
      MET. We found that p53 restricts MET during the early phases of reprogramming and
      that this effect is primarily mediated by the ability of p53 to inhibit Klf4
      dependent activation of epithelial genes. Moreover, transcriptome analysis
      revealed a large transcriptional signature enriched with epithelial genes, which
      is markedly induced by Klf4 exclusively in p53(-/-) cells. We also found that the
      expression of the epithelial marker E-Cadherin negatively correlates with p53
      activity in a variety of mesenchymal cells even before the expression of
      reprogramming factors. Finally, we demonstrate that the inhibitory effect of p53
      on MET is mediated by p21. We conclude that inhibition of the p53-p21 axis
      predisposes mesenchymal cells to the acquisition of epithelial characteristics
      and renders them more prone to reprogramming. Our study uncovers a novel
      mechanism by which p53 restrains reprogramming and highlights the role of p53 in
      regulating cell plasticity.

PMID- 22996685
TI  - Potential carcinogenic effects of world trade center dust after intratracheal
      instillation to Sprague-Dawley rats: first observation.
AB  - BACKGROUND: More than 10 years have passed since the terrorist attack on the New
      York City World Trade Center on September 11, 2001. It is well known that long
      term carcinogenic bioassays on rodents can predict the potential carcinogenic
      effects of chemical and physical agents for humans. OBJECTIVE: A life-span
      carcinogenicity bioassay was conducted on Sprague-Dawley rats at the CMCRC of the
      Ramazzini Institute to test the potential carcinogenic effects of settled dust
      collected at the WTC immediately after the terrorist attack. METHODS: The WTC
      material tested is a complex mixture of coarse particles (95%) contain pulverized
      cement, glass fibres, asbestos, lead, polycyclic aromatic hydrocarbons (PAH(S) ),
      polychlorinated biphenyls (PCB(S) ) and polychlorinated furans, and dioxin. The
      test matter was suspended in sterile saline and administered by intratracheal
      instillation (IT) to 8-week-old Sprague-Dawley rats (100 animals/sex), 3-4
      days/week for 4 weeks. A group of 200 male and female rats served as controls.
      The animals were kept under observation until natural death. RESULTS:
      Histopathological evaluation of the lungs (target organ) of instilled control and
      treated male and female rats, did not show any significant increased incidence of
      lung tumors. Two hemangiomas (one with endothelial atypia) and one
      hemangiosarcoma were found in the lungs of treated males. Moreover a modest
      increased incidence of terminal bronchiolar hyperplasia (TBH) and squamous
      metaplasia occurred in the lung of treated males and females compared to the
      controls. CONCLUSION: Hemangioma and hemangiosarcoma are extremely rare tumors in
      the lung of our colony and we believe they are caused by WTC dust.

PMID- 22996686
TI  - Delayed radical prostatectomy for intermediate-risk prostate cancer is associated
      with biochemical recurrence: possible implications for active surveillance from
      the SEARCH database.
AB  - INTRODUCTION: Active surveillance (AS) is increasingly accepted as appropriate
      management for low-risk prostate cancer (PC) patients. It is unknown whether
      delaying radical prostatectomy (RP) is associated with increased risk of
      biochemical recurrence (BCR) for men with intermediate-risk PC. METHODS: We
      performed a retrospective analysis of 1,561 low and intermediate-risk men from
      the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated with
      RP between 1988 and 2011. Patients were stratified by interval between diagnosis
      and RP (<= 3, 3-6, 6-9, or >9 months) and by risk using the D'Amico
      classification. Cox proportional hazard models were used to analyze BCR. Logistic
      regression was used to analyze positive surgical margins (PSM), extracapsular
      extension (ECE), and pathologic upgrading. RESULTS: Overall, 813 (52%) men were
      low-risk, and 748 (48%) intermediate-risk. Median follow-up among men without
      recurrence was 52.9 months, during which 437 men (38.9%) recurred. For low-risk
      men, RP delays were unrelated to BCR, ECE, PSM, or upgrading (all P > 0.05). For
      intermediate-risk men, however, delays >9 months were significantly related to
      BCR (HR: 2.10, P = 0.01) and PSM (OR: 4.08, P < 0.01). Delays >9 months were
      associated with BCR in subsets of intermediate-risk men with biopsy Gleason score
      <= 3 + 4 (HR: 2.51, P < 0.01), PSA <= 6 (HR: 2.82, P = 0.06), and low tumor
      volume (HR: 2.59, P = 0.06). CONCLUSIONS: For low-risk men, delayed RP did not
      significantly affect outcome. For men with intermediate-risk disease, delays >9
      months predicted greater BCR and PSM risk. If confirmed in future studies, this
      suggests delayed RP for intermediate-risk PC may compromise outcomes.

PMID- 22996687
TI  - The structure of the fruit peel in two varieties of Malus domestica Borkh.
      (Rosaceae) before and after storage.
AB  - The structure of fruit peel of two apple varieties 'Szampion' and 'Jonagold' was
      investigated using light microscopy as well as scanning and transmission electron
      microscopy. The samples were taken immediately after harvest and after 6-month
      controlled atmosphere storage. The Szampion and Jonagold fruit differed in terms
      of the surface type, number of lenticels, thickness of the cuticular epithelium,
      height of epidermal cells and thickness of the hypodermis as well as the amount
      of crystalline wax and the number of microcracks formed on the fruit surface. The
      6-month storage resulted in fruit weight loss, increased numbers and depth of
      microcracks, thickening of the amorphous wax layer and enhanced production of
      platelet forms of crystalline wax, which filled the microcracks abundantly.
      Compared with Jonagold, the Szampion fruit exhibited a fewer lenticels, a bigger
      number of microcracks, smaller amounts of crystalline wax and more substantial
      weight loss. The apple varieties studied had a reticulate-lamellate cuticle, and
      at harvest, the epidermal and hypodermal cells contained numerous amyloplasts
      filled with starch grains, which were not found after the storage period.
      Additionally, after storage, the cell protoplasts in the apple peel displayed a
      disorganised structure, and their vacuoles contained fragments of cell membranes,
      intravacuolar precipitates and deposits, and spherical bodies. The results may
      facilitate better understanding of changes occurring in fruits of Szampion and
      Jonagold during storage and help choose the best storage conditions to reduce
      loss of weight and prevent impairment of fruit quality.

PMID- 22996688
TI  - BD PuraMatrix peptide hydrogel as a culture system for human fetal Schwann cells
      in spinal cord regeneration.
AB  - BD PuraMatrix peptide hydrogel, a three-dimensional cell culture model of
      nanofiber scaffold derived from the self-assembling peptide RADA16, has been
      applied to regenerative tissue repair in order to develop novel nanomedicine
      systems. In this study with PuraMatrix, self-assembling nanofiber scaffold
      (SAPNS) and Schwann cells (SCs) were isolated from human fetal sciatic nerves,
      cultured within SAPNS, and then transplanted into the spinal cord after injury
      (SCI) in rats. First, the peptide nanofiber scaffold was evaluated via scanning
      electron microscopy and atomic force microscopy. With phase-contrast microscopy,
      the appearance of representative human fetal SCs encapsulated in PuraMatrix on
      days 3, 5, and 7 in 12-well plates was revealed. The Schwann cells in PuraMatrix
      were cultured for 2 days, and the SCs had active proliferative potential. Spinal
      cord injury was induced by placing a 35-g weight on the dura of T9-T10 segments
      for 15 min, followed by in vivo treatment with SAPNS and human fetal SCs (100,000
      cells/10 MUl/injection) grafted into spinal cord 7 days after SCI. After
      treatment, the recovery of motor function was assessed periodically using the
      Basso, Beattie, and Bresnahan scoring system. Eight weeks after grafting, animals
      were perfusion fixed, and the survival of implanted cells was analyzed with
      antibody recognizing SCs. Immunohistochemical analysis of grafted lumber segments
      at 8 weeks after grafting revealed reduced asterogliosis and considerably
      increased infiltration of endogenous S100(+) cells into the injury site,
      suggesting that PuraMatrix may play an important role in the repair observed
      after SAPNS and human fetal SC transplantation.

PMID- 22996689
TI  - Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling.
AB  - The osteoporosis associated with human hyperthyroidism has traditionally been
      attributed to elevated thyroid hormone levels. There is evidence, however, that
      thyroid-stimulating hormone (TSH), which is low in most hyperthyroid states,
      directly affects the skeleton. Importantly, Tshr-knockout mice are osteopenic. In
      order to determine whether low TSH levels contribute to bone loss in
      hyperthyroidism, we compared the skeletal phenotypes of wild-type and Tshr
      knockout mice that were rendered hyperthyroid. We found that hyperthyroid mice
      lacking TSHR had greater bone loss and resorption than hyperthyroid wild-type
      mice, thereby demonstrating that the absence of TSH signaling contributes to bone
      loss. Further, we identified a TSH-like factor that may confer osteoprotection.
      These studies suggest that therapeutic suppression of TSH to very low levels may
      contribute to bone loss in people.

PMID- 22996690
TI  - Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets.
AB  - Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis.
      The lack of an animal model for CF-related diabetes (CFRD) has made it difficult
      to dissect how the onset of pancreatic pathology influences the emergence of
      CFRD. We evaluated the structure and function of the neonatal CF endocrine
      pancreas using a new CFTR-knockout ferret model. Although CF kits are born with
      only mild exocrine pancreas disease, progressive exocrine and endocrine
      pancreatic loss during the first months of life was associated with pancreatic
      inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly,
      prior to major exocrine pancreas disease, CF kits demonstrated significant
      abnormalities in blood glucose and insulin regulation, including diminished first
      phase and accentuated peak insulin secretion in response to glucose, elevated
      peak glucose levels following glucose challenge, and variably elevated insulin
      and C-peptide levels in the nonfasted state. Although there was no difference in
      lobular insulin and glucagon expression between genotypes at birth, significant
      alterations in the frequencies of small and large islets were observed. Newborn
      cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion
      in comparison to controls, suggesting intrinsic abnormalities in CF islets. These
      findings demonstrate that early abnormalities exist in the regulation of insulin
      secretion by the CF endocrine pancreas.

PMID- 22996691
TI  - Myocardin regulates BMP10 expression and is required for heart development.
AB  - Myocardin is a muscle lineage-restricted transcriptional coactivator that has
      been shown to transduce extracellular signals to the nucleus required for SMC
      differentiation. We now report the discovery of a myocardin/BMP10 (where BMP10
      indicates bone morphogenetic protein 10) signaling pathway required for cardiac
      growth, chamber maturation, and embryonic survival. Myocardin-null (Myocd)
      embryos and embryos harboring a cardiomyocyte-restricted mutation in the Myocd
      gene exhibited myocardial hypoplasia, defective atrial and ventricular chamber
      maturation, heart failure, and embryonic lethality. Cardiac hypoplasia was caused
      by decreased cardiomyocyte proliferation accompanied by a dramatic increase in
      programmed cell death. Defective chamber maturation and the block in
      cardiomyocyte proliferation were caused in part by a block in BMP10 signaling.
      Myocardin transactivated the Bmp10 gene via binding of a serum response factor
      myocardin protein complex to a nonconsensus CArG element in the Bmp10 promoter.
      Expression of p57kip2, a BMP10-regulated cyclin-dependent kinase inhibitor, was
      induced in Myocd-/- hearts, while BMP10-activated cardiogenic transcription
      factors, including NKX2.5 and MEF2c, were repressed. Remarkably, when embryonic
      Myocd-/- hearts were cultured ex vivo in BMP10-conditioned medium, the defects in
      cardiomyocyte proliferation and p57kip2 expression were rescued. Taken together,
      these data identify a heretofore undescribed myocardin/BMP10 signaling pathway
      that regulates cardiomyocyte proliferation and apoptosis in the embryonic heart.

PMID- 22996692
TI  - Mutant huntingtin fragmentation in immune cells tracks Huntington's disease
      progression.
AB  - Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused
      by an expanded CAG repeat in the gene encoding huntingtin (HTT). Therapeutic
      approaches to lower mutant HTT (mHTT) levels are expected to proceed to human
      trials, but noninvasive quantification of mHTT is not currently possible. The
      importance of the peripheral immune system in neurodegenerative disease is
      becoming increasingly recognized. Peripheral immune cells have been implicated in
      HD pathogenesis, but HTT levels in these cells have not been quantified before. A
      recently described time-resolved Forster resonance energy transfer (TR-FRET)
      immunoassay was used to quantify mutant and total HTT protein levels in
      leukocytes from patients with HD. Mean mHTT levels in monocytes, T cells, and B
      cells differed significantly between patients with HD and controls and between
      pre-manifest mutation carriers and those with clinical onset. Monocyte and T cell
      mHTT levels were significantly associated with disease burden scores and caudate
      atrophy rates in patients with HD. mHTT N-terminal fragments detected in HD PBMCs
      may explain the progressive increase in mHTT levels in these cells. These
      findings indicate that quantification of mHTT in peripheral immune cells by TR
      FRET holds significant promise as a noninvasive disease biomarker.

PMID- 22996693
TI  - CXCR1/2 inhibition enhances pancreatic islet survival after transplantation.
AB  - Although long considered a promising treatment option for type 1 diabetes,
      pancreatic islet cell transformation has been hindered by immune system rejection
      of engrafted tissue. The identification of pathways that regulate post-transplant
      detrimental inflammatory events would improve management and outcome of
      transplanted patients. Here, we found that CXCR1/2 chemokine receptors and their
      ligands are crucial negative determinants for islet survival after
      transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and
      CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were
      strongly induced shortly after islet infusion. Genetic and pharmacological
      blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet
      engraftment and reduced intrahepatic recruitment of polymorphonuclear leukocytes
      and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor
      reparixin improved outcome in a phase 2 randomized, open-label pilot study with a
      single infusion of allogeneic islets. These findings indicate that the CXCR1/2
      mediated pathway is a regulator of islet damage and should be a target for
      intervention to improve the efficacy of transplantation.

PMID- 22996696
TI  - One-pot synthesis, characterization, and enhanced photocatalytic activity of a
      BiOBr-graphene composite.
AB  - Herein, a chemically bonded BiOBr-graphene composite (BiOBr-RG) was prepared
      through a facile in situ solvothermal method in the presence of graphene oxide.
      Graphene oxide could be easily reduced to graphene under solvothermal conditions,
      and simultaneously BiOBr nanoplates with pure tetragonal phase were grown
      uniformly on the graphene surface. The structure and photoelectrochemical
      properties of the resulting materials were characterized by transmission electron
      microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR)
      spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and
      impedance and photocurrent action measurements. The combination of BiOBr and
      graphene introduces some properties of graphene into the photocatalysis reaction,
      such as excellent conductivity, adsorptivity, and controllability. A remarkable
      threefold enhancement in the degradation of rhodamine B (RhB) was observed with
      as-prepared BiOBr-RG as compared with pure BiOBr under visible light (lambda>420
      nm). The enhanced photocatalytic activity could be attributed to the great
      adsorptivity of dyes, the extended photoresponse range, the negative shift in the
      Fermi level of BiOBr-RG, and the high migration efficiency of photoinduced
      electrons, which may effectively suppress the charge recombination.

PMID- 22996694
TI  - Recombinant IL-7/HGFbeta efficiently induces transplantable murine hematopoietic
      stem cells.
AB  - Difficulty obtaining sufficient hematopoietic stem cells (HSCs) directly from the
      donor has limited the clinical use of HSC transplantation. Numerous attempts to
      stimulate the ex vivo growth of purified HSCs with cytokines and growth factors
      generally have induced only modest increases in HSC numbers while decreasing
      their in vivo reconstituting ability. We previously developed a recombinant
      single-chain form of a naturally occurring murine hybrid cytokine of IL-7 and the
      beta chain of hepatocyte growth factor (rIL-7/HGFbeta) that stimulates the in
      vitro proliferation and/or differentiation of common lymphoid progenitors, pre
      pro-B cells, and hematopoietic progenitor cells (day 12 spleen colony-forming
      units) in cultures of mouse BM. Here we used the rIL-7/HGFbeta in culture to
      induce large numbers of HSCs from multiple cell sources, including unseparated BM
      cells, purified HSCs, CD45- BM cells, and embryonic stem cells. In each instance,
      most of the HSCs were in the G0 phase of the cell cycle and exhibited reduced
      oxidative stress, decreased apoptosis, and increased CXCR4 expression.
      Furthermore, when injected i.v., these HSCs migrated to BM, self-replicated,
      provided radioprotection, and established long-term hematopoietic reconstitution.
      These properties were amplified by injection of rIL-7/HGFbeta directly into the
      BM cavity but not by treatment with rIL-7, rHGF, and/or rHGFbeta.

PMID- 22996697
TI  - A microfabricated platform to form three-dimensional toroidal multicellular
      aggregate.
AB  - Techniques that allow cells to self-assemble into three-dimensional (3D) spheroid
      microtissues provide powerful in vitro models that are becoming increasingly
      popular in fields such as stem cell research, tissue engineering, and cancer
      biology. Appropriate simulation of the 3D environment in which tissues normally
      develop and function is crucial for the engineering of in vitro models that can
      be used for the formation of complex tissues. We have developed a unique
      multicellular aggregate formation platform that utilizes a maskless gray-scale
      photolithography. The cellular aggregate formed using this platform has a
      toroidal-like geometry and includes a micro lumen that facilitates the supply of
      oxygen and growth factors and the expulsion of waste products. As a result, this
      platform was capable of rapidly producing hundreds of multicellular aggregates at
      a time, and of regulating the diameter of aggregates with complex design. These
      toroidal multicellular aggregates can grow as long-term culture. In addition, the
      micro lumen can be used as a continuous channel and for the insertion of a
      vascular system or a nerve system into the assembled tissue. These platform
      characteristics highlight its potential to be used in a wide variety of
      applications, e.g. as a bioactuator, as a micro-machine component or in drug
      screening and tissue engineering.

PMID- 22996695
TI  - The ADP receptor P2RY12 regulates osteoclast function and pathologic bone
      remodeling.
AB  - The adenosine diphosphate (ADP) receptor P2RY12 (purinergic receptor P2Y, G
      protein coupled, 12) plays a critical role in platelet aggregation, and P2RY12
      inhibitors are used clinically to prevent cardiac and cerebral thrombotic events.
      Extracellular ADP has also been shown to increase osteoclast (OC) activity, but
      the role of P2RY12 in OC biology is unknown. Here, we examined the role of mouse
      P2RY12 in OC function. Mice lacking P2ry12 had decreased OC activity and were
      partially protected from age-associated bone loss. P2ry12-/- OCs exhibited intact
      differentiation markers, but diminished resorptive function. Extracellular ADP
      enhanced OC adhesion and resorptive activity of WT, but not P2ry12-/-, OCs. In
      platelets, ADP stimulation of P2RY12 resulted in GTPase Ras-related protein
      (RAP1) activation and subsequent alphaIIbbeta3 integrin activation. Likewise, we
      found that ADP stimulation induced RAP1 activation in WT and integrin beta3 gene
      knockout (Itgb3-/-) OCs, but its effects were substantially blunted in P2ry12-/-
      OCs. In vivo, P2ry12-/- mice were partially protected from pathologic bone loss
      associated with serum transfer arthritis, tumor growth in bone, and ovariectomy
      induced osteoporosis: all conditions associated with increased extracellular ADP.
      Finally, mice treated with the clinical inhibitor of P2RY12, clopidogrel, were
      protected from pathologic osteolysis. These results demonstrate that P2RY12 is
      the primary ADP receptor in OCs and suggest that P2RY12 inhibition is a potential
      therapeutic target for pathologic bone loss.

PMID- 22996698
TI  - Dry matter intake and digestibility of rations replacing concentrates with graded
      levels of Enterolobium cyclocarpum in Pelibuey lambs.
AB  - The aim of the study was to evaluate the effect of graded levels of Enterolobium
      cyclocarpum pods in the ration on feed intake and digestibility by Pelibuey
      lambs. Five dietary treatments were imposed where ground pods replaced
      concentrate diet at 0, 20, 30, 40 and 50 % of dry matter (DM), respectively. The
      concentrate portion was composed of ground sorghum, soybean meal, cane molasses
      and minerals. Five entire Pelibuey lambs with initial bodyweight 34 +/- 2 kg were
      allocated in the treatments in a 5 * 5 Latin square design. Values of dry matter
      intake (DMI) and dry matter (DMD) and organic matter (OMD) digestibility were
      measured and metabolisable energy intake (MEI) estimated. Rumen degradation
      constants for E. cyclocarpum were also measured. There were no differences (P >
      0.05) in average DMI (86.6 g/kg(0.75)) and OMI (81.2 g/kg(0.75)) among
      treatments. As the level of incorporation of E. cyclocarpum pods increased,
      voluntary DMI and OMI increased, whereas apparent DMD and OMD decreased linearly.
      Average digestible DM (65 g/kg(0.75)) and OM (61 g/kg(0.75)) intakes were similar
      (P > 0.05) among treatments. Similarly, MEI (0.976 MJ ME kg(0.75)/day) was not
      different (P > 0.05) among treatments. The potential rumen degradation (A + B) of
      ground pods of E. cyclocarpum was 866.4 g/kg DM. Ground pods of E. cyclocarpum
      can be employed for lamb feeding up to 50 % of the ration, without affecting DMI,
      DM apparent digestibility and MEI.

PMID- 22996700
TI  - Dual hard/soft gold catalysis: intermolecular Friedel-Crafts-type alpha
      amidoalkylation/alkyne hydroarylation sequences by N-acyliminium ion chemistry.
AB  - Gold catalysts have been applied in cascade-type reactions for the synthesis of
      different nitrogen-based compounds. The reactions likely proceed by a new gold
      catalyzed cascade intermolecular alpha-amidoalkylation/intramolecular
      carbocyclization cascade process by unifying both the sigma- and pi-Lewis acid
      properties of the gold salts. In the first part of this report we show that the
      sigma-Lewis acidity of gold(I) and gold(III) could be exploited to efficiently
      catalyze the nucleophilic substitution of various alkoxy- and acetoxylactams. The
      reaction was found to be applicable to a wide range of cyclic N-acyliminium ion
      precursors and various nucleophiles, including allyltrimethylsilane, silyl enol
      ethers, arenes, and active methylene derivatives. As a logical progression of
      this study, a combined hard/soft binary catalytic gold system was then used to
      implement an unprecedented tandem intermolecular Friedel-Crafts
      amidoalkylation/intramolecular hydroarylation sequence allowing an expedient
      access to new, complex, fused polyheterocyclic structures from trivial materials.

PMID- 22996699
TI  - Role of bis(monoacylglycero)phosphate in propranolol binding to phospholipid
      membranes under acidic conditions as measured by high-performance frontal
      analysis/capillary electrophoresis.
AB  - Bis(monoacylglycero)phosphate (BMP) is localized in acidic organelles such as
      late endosomes or lysosomes. It has been reported that BMP levels increase under
      phospholipidosis induced by cationic amphiphilic drugs. In the present study, the
      effect of BMP on the binding of propranolol (PRO) to phospholipid liposomes under
      acidic conditions was investigated. Binding experiments were conducted by high
      performance frontal analysis/capillary electrophoresis. PRO showed nonspecific
      binding to BMP-containing liposomes (BMP:phosphatidylcholine = 1:4), when numbers
      of bound drug molecules per lipid molecule (r) ranged 0.01-0.06. Total binding
      affinity increased depending on the BMP content. Binding affinity was decreased
      by low ionic strength, or by substitution of BMP with diacylglycerol, suggesting
      that electrostatic interactions were involved. The binding-enhancement effect of
      BMP was almost equivalent to that of phosphatidylglycerol, and slightly larger
      than that of phosphatidylserine. An acidic environment (pH 5.0) decreased total
      binding affinity to BMP-containing liposomes. This could be explained by the pH
      partition theory (i.e., the loss in affinity was caused by a decrease in the
      neutral form of the drug accessible to the membrane core). These results suggest
      that PRO binding is enhanced by BMP in late endosomes or lysosomes, whereas an
      acidic environment weakens such binding.

PMID- 22996703
TI  - Medical research in a changing world: research needs, opportunities, and
      imperatives in otolaryngology-head and neck surgery.

PMID- 22996702
TI  - Social competence and empathy in young children with cochlear implants and with
      normal hearing.
AB  - OBJECTIVES: To examine the levels of social competence and empathic behavior in
      children with cochlear implants in comparison with normal-hearing children, and
      to determine whether empathy predicts social competence to the same extent in
      both groups of children. STUDY DESIGN: Retrospective cohort study. METHODS: A
      total of 150 children (mean age 39 months) participated in the study; 61 with
      cochlear implants and 89 without hearing loss. Parent reports and observation
      measures were employed to measure empathy and social competence. RESULTS: Levels
      of empathy and social competence in children with cochlear implants and normal
      hearing children were similar. Empathic behaviors were predictive of social
      competence in both groups alike. Emotion acknowledgment was more predictive of
      social competence for children with cochlear implants than for normal-hearing
      children. Language skills were unrelated to social competence or empathic
      behaviors in children with cochlear implants. CONCLUSIONS: Children with cochlear
      implants showed no delay concerning social competence or empathic behavior. The
      factors contributing to social competence, however, differed between the groups.
      This should be kept in mind when developing rehabilitation programs for children
      with cochlear implants.

PMID- 22996704
TI  - Bilateral hemotympanum secondary to septoplasty.

PMID- 22996705
TI  - Unusual maxillary chondrosarcoma.

PMID- 22996706
TI  - Salivary duct carcinoma.

PMID- 22996707
TI  - Bilateral posterior semicircular canal dehiscence in the setting of Hallermann
      Streiff syndrome.
AB  - Hallermann-Streiff syndrome, also known as oculomandibulofacial syndrome, is a
      rare congenital disorder affecting growth and cranial, dental, ocular,
      pilocutaneous, and mental development. In addition to routine audiologic testing
      in patients with this syndrome, high-resolution computed tomography of the
      temporal bones should be performed in those with documented or suspected
      sensorineural hearing loss. Cochlear implantation may be considered, as in other
      children with syndromic hearing loss and certain inner ear abnormalities, if the
      appropriate audiologic, psychosocial, and medical criteria are met. The current
      case report radiographically and clinically characterizes inner ear dysplasia in
      an 8-year-old patient with Hallermann-Streiff syndrome. High-resolution computed
      tomography of the temporal bones revealed a hypoplastic bony island between the
      vestibule and horizontal semicircular canals, as well as incomplete bony coverage
      of the posterior semicircular canal crura bilaterally. To our knowledge, this is
      the first report of a pediatric patient demonstrating bilateral posterior
      semicircular canal dehiscence.

PMID- 22996708
TI  - Juvenile xanthogranuloma of the tympanic membrane: a case report.
AB  - Juvenile xanthogranuloma (JXG) is a benign, non-Langerhans cell histiocytic
      lesion that generally affects infants and children. These lesions
      characteristically appear as a solitary, yellow, cutaneous nodule of the head,
      neck, or trunk. Subcutaneous and extracutaneous forms can involve the
      gastrointestinal tract, kidney, lung, gonads, pericardium, central nervous
      system, temporal bone, larynx, and eye. We describe the clinical presentation,
      imaging, histochemical findings, and management of a solitary JXG of the tympanic
      membrane in a 17-month-old girl. The patient underwent surgical resection and was
      without disease several months following surgery and reconstruction of the
      defect. To the best of our knowledge, this is the first reported case of a JXG of
      the tympanic membrane.

PMID- 22996709
TI  - The effect of chronic obstructive pulmonary disease on laryngopharyngeal
      sensitivity.
AB  - Patients with chronic obstructive pulmonary disease (COPD) may be at increased
      risk of aspiration secondary to impaired swallow function. One possible cause of
      this impairment is a reduction in laryngopharyngeal sensitivity. The relationship
      between COPD and laryngopharyngeal sensitivity has not been previously
      determined. We conducted a study to investigate the effect of COPD on
      laryngopharyngeal sensitivity by using laryngopharyngeal sensory discrimination
      testing (LPSDT). Our study population was made up of 20 adults (mean age: 71.7
      yr) with clinically proven COPD and 11 healthy, age-matched controls. All 31
      subjects underwent LPSDT with the use of an air-pulse stimulator via a
      nasendoscope. The threshold of laryngopharyngeal sensation was evaluated by
      measuring the amount of air pressure required to elicit the laryngeal adductor
      reflex (LAR). We found that the patients with COPD had a significantly higher LAR
      threshold than did the controls (p< 0.001). We conclude that patients with COPD
      have significantly less mechanosensitivity in the laryngopharynx. This sensory
      change may place patients with COPD at increased risk for aspiration.

PMID- 22996710
TI  - Puffed-cheek computed tomography: a dynamic maneuver for imaging oral cavity
      tumors.
AB  - We conducted a prospective study to compare the effectiveness of conventional
      computed tomography (CT) and puffed-cheek CT in detecting the presence and
      extension of oral cavity malignant tumors. We enrolled 11 patients--5 men and 6
      women, aged 32 to 85 years--who had a primary squamous cell carcinoma of the oral
      cavity. These tumors were located in the floor of the mouth in 4 patients, in the
      buccal mucosa in 4, in both the buccal mucosa and retromolar trigone in 2, and in
      the retromolar trigone only in 1. First, conventional contrast-enhanced axial CT
      was obtained through the oral cavity and neck in each patient. Next, axial
      imaging was obtained through the oral cavity while patients inflated their
      cheeks, pursed their lips, and held their breath. We found that the puffed-cheek
      CTs provided more information regarding the size and extent of the squamous cell
      carcinomas than did the conventional CTs. For example, in 8 patients,
      conventional CT could not differentiate the tumor from the normal mucosal
      surface, but puffed-cheek images clearly showed the surface of the tumor as
      distinct from the normal mucosa. More disconcerting was the fact that in the
      other 3 patients, conventional CTs were evaluated as normal, even though puffed
      cheek imaging clearly showed the mass in each case. We conclude that puffed-cheek
      CT is superior to conventional CT for evaluating the mucosal surfaces of the oral
      cavity. It provides a clearer and more detailed picture with no downside.

PMID- 22996711
TI  - Prostate cancer metastatic to the larynx: a case report.
AB  - Prostate cancer, which is the most common cancer among men, rarely metastasizes
      to the neck. We report a case of prostatic carcinoma that metastasized to the
      larynx in a 71-year-old man who presented with hoarseness and shortness of
      breath. Computed tomography (CT) detected a 2.9 * 3.1 * 2.6-cm mass that extended
      from the cricoid and arytenoid cartilages into the superior trachea. Findings on
      histopathology and immunohistochemistry of the laryngeal tumor were consistent
      with a metastasis of the patient's earlier prostate cancer. CT of the chest later
      detected a soft-tissue mass in the right paraspinal area and other thoracic
      pathology that represented metastatic disease. The patient was treated with
      palliative radiation therapy. As androgen deprivation therapy continues to
      increase the life expectancy of prostate cancer patients, detection of distant
      metastases will likely increase, as well. Urogenital cancer metastatic to the
      head and neck should be considered in the differential diagnosis of laryngeal
      masses.

PMID- 22996712
TI  - Tracheal carcinoid presenting as refractory cervicalgia in a postpartum patient:
      correlation versus epiphenomenon.
AB  - Primary tracheal carcinoid tumor is an extremely rare disorder that has been
      reported only occasionally in the medical literature. We report a case of a 36
      year-old African American woman who presented to the emergency department
      complaining of persistent neck pain for the preceding week. She was 2 weeks
      postpartum and had no significant medical history. Laboratory workup was
      unremarkable. Computed tomography and magnetic resonance imaging showed a
      polypoid mass in the trachea. After bronchoscopy and laser ablation of the mass
      were performed, the final diagnosis of carcinoid tumor was made. To our knowledge
      this is the first reported case of this tumor in a postpartum patient. Further
      studies regarding the interactions between the natural history of carcinoid
      tumors and pregnancy are warranted. Their infrequency, clinical features, and
      pathophysiology make tracheal carcinoid tumors a formidable and interesting
      diagnostic challenge.

PMID- 22996713
TI  - Otogenic pneumocephalus as a complication of multiple myeloma.
AB  - We report a case of otogenic pneumocephalus in an 80-year-old woman with multiple
      myeloma. The pneumocephalus was associated with Haemophilus influenzae otitis
      media and reactive meningitis in the absence of an intracranial brain abscess.
      Myeloma causes thinning of bone trabeculae and destructive lytic bone lesions.
      This can predispose to a risk of pathologic fractures and, in patients with skull
      vault involvement, to the rare complication of pneumocephalus. Therefore,
      pneumocephalus should be considered in the differential diagnosis of acute
      headache in patients with multiple myeloma, especially those with skull vault
      involvement. Prompt computed tomography and liaison between the otolaryngology
      and neurology teams may assist in making an early diagnosis and preventing life
      threatening intracranial complications.

PMID- 22996714
TI  - Mandibular condyle reconstruction with fibula free-tissue transfer.
AB  - We conducted a study to evaluate functional and cosmetic outcomes following
      reconstruction of the mandibular condyle with direct placement of a vascularized
      free fibula. We retrospectively reviewed the cases of all patients who had
      undergone hemimandibulectomy and condyle resection with immediate reconstruction
      at the Mayo Clinic in Rochester, Minn., between Nov. 1, 2005, and Jan. 31, 2007.
      We found 7 such cases, all of which occurred in men aged 32 to 61 years (mean:
      50.7). Six of these patients had a malignancy and 1 had osteomyelitis.
      Postoperatively, 6 patients had no difficulty with occlusion, which was rated as
      "good" or "excellent" at their 6-month follow-up visit; the other patient had an
      open-bite deformity, but he was able to masticate solid food and maintain an oral
      diet. Cosmesis was generally satisfactory, and all patients maintained
      intelligible speech. We conclude that free fibula transfer with direct seating of
      the fibula into the condylar fossa followed by aggressive physiotherapy provides
      acceptable functional reconstruction of the mandibulectomy-condylectomy defect.

PMID- 22996715
TI  - Traumatic thyroid hematoma associated with thyroid carcinoma.
AB  - Thyroid hematoma secondary to blunt trauma is uncommon, and no consensus exists
      for its management. We describe the case of a 46-year-old man who presented with
      neck swelling after he had sustained a blunt-trauma injury to his neck while
      playing soccer. Imaging revealed a large mass consistent with a thyroid hematoma.
      The patient was admitted for observation and followed up with serial imaging. He
      was eventually discharged without surgical intervention. However, he later
      underwent a thyroid lobectomy to treat compressive symptoms and for cosmetic
      reasons. Pathology revealed that the patient had a papillary thyroid carcinoma,
      which might have predisposed him to the hemorrhage. Thyroid hematoma secondary to
      blunt trauma has been documented in normal thyroid glands and in glands with
      preexisting benign pathology, but to the best of our knowledge, no report
      associating this condition with a thyroid carcinoma has previously been reported
      in the literature. A neoplasm should be suspected in a case of thyroid hematoma
      that fails to resolve with conservative treatment. The management of this
      condition is surgeon- and case-specific, and the overall prognosis is good.

PMID- 22996716
TI  - Clindamycin-induced neutropenia following major head and neck surgery.
AB  - A 64-year-old man undergoing major head and neck surgery received clindamycin for
      perioperative antimicrobial prophylaxis. On the third postoperative day, he
      became acutely neutropenic. The neutropenia resolved 3 days later, after the
      administration of filgrastim. After ruling out other causes of acute neutropenia,
      we determined that the neutropenia was secondary to clindamycin toxicity. While
      clindamycin-induced neutropenia has been reported elsewhere, to our knowledge
      this is the first report of its occurrence following head and neck surgery.
      Otolaryngologists should be aware of this potentially serious reaction.

PMID- 22996717
TI  - Dysphagia after strangulation.

PMID- 22996718
TI  - Endoscopic view of bilateral maxillary sinus cysts removed with a powered
      instrument.

PMID- 22996719
TI  - Osseous metaplasia in a nasal polyp: report of a rare case and review of the
      literature.
AB  - Metaplasia is the conversion of one adult tissue or cell type into another tissue
      or cell type. Although osseous metaplasia has been described in many parts of the
      body, it is rarely encountered in the head and neck region, especially in nasal
      polyps. This article reports a case of unilateral sinonasal polyp containing
      areas of osseous metaplasia in a 44-year-old woman presenting with nasal
      obstruction. Also included are a brief discussion of osseous metaplasia in the
      head and neck region and a literature review.

PMID- 22996720
TI  - Adult extracardiac rhabdomyoma of the parapharyngeal space.
AB  - Adult extracardiac rhabdomyoma (ER) is a rare, slowly growing, benign tumor of
      skeletal-muscle origin that has a strong predilection for the head and neck.
      Complete surgical resection has been proposed as the treatment of choice. We
      describe a case of adult ER that manifested as a nasopharyngeal mass. The
      diagnosis was made by transnasal endoscopic biopsy, and the patient was managed
      conservatively. We discuss the current knowledge regarding the clinical
      presentation, diagnosis, and treatment of adult ER of the parapharyngeal space,
      and we propose a new concept for treating this tumor nonsurgically in
      appropriately selected patients.

PMID- 22996722
TI  - Evaluating dynamic effects of copy number alterations on gene expression using a
      single transcription model.
AB  - DNA copy number alterations (CNAs) are known to be related to genetic diseases,
      including cancer. The unlimited transcription (UT) model, in which transcription
      occurs permissively with a simple activation probability, has been proposed to
      investigate long-term effects of CNAs on gene expression values. Queueing theory
      was applied, and the copy-number-gene-expression relationship has been shown to
      be generally nonlinear in the UT model. However, the dynamic effects of CNAs on
      transcription and the underlying disorders related to diseases remain greatly
      unknown. Since most genes in a single cell are permissively transcribed in short
      periods of time interspersed by long periods of limited transcription, an
      alternative model for transcription in the restrictive state is needed for
      unraveling the effects of CNAs on gene expression levels with time. To address
      these issues, herein a single transcription (ST) model is proposed, in which
      bound TFs are assumed to be unloaded immediately after stimulating a
      transcription. Using the Laplace-Stieltjes transform and numerical analysis, the
      relationship between DNA copy number and gene expression level is evaluated.
      Dynamic modeling reveals that CNAs would potentially alter, or even reverse, the
      burst-like gene expression modifications while shifting from the ST model to the
      UT model. Moreover, functional disorders in transcriptional oscillation due to
      CNAs are shown via simulation. This paper demonstrates how mathematical theories
      could be helpful to interpret statistical findings from real data and achieve a
      better understanding of cancer biology.

PMID- 22996721
TI  - Toward design of an environment-aware adaptive locomotion-mode-recognition
      system.
AB  - In this study, we aimed to improve the performance of a locomotion-mode
      recognition system based on neuromuscular-mechanical fusion by introducing
      additional information about the walking environment. Linear-discriminant
      analysis-based classifiers were first designed to identify a lower limb
      prosthesis user's locomotion mode based on electromyographic signals recorded
      from residual leg muscles and ground reaction forces measured from the prosthetic
      pylon. Nine transfemoral amputees who wore a passive hydraulic knee or powered
      prosthetic knee participated in this study. Information about the walking terrain
      was simulated and modeled as prior probability based on the principle of maximum
      entropy and integrated into the discriminant functions of the classifier. When
      the correct prior knowledge of walking terrain was simulated, the classification
      accuracy for each locomotion mode significantly increased and no task transitions
      were missed. In addition, simulated incorrect prior knowledge did not
      significantly reduce system performance, indicating that our design is robust
      against noisy and imperfect prior information. Furthermore, these observations
      were independent of the type of prosthesis applied. The promising results in this
      study may assist the further development of an environment-aware adaptive system
      for locomotion-mode recognition for powered lower limb prostheses or orthoses.

PMID- 22996723
TI  - Development of an AMR-ACB array for gastrointestinal motility studies.
AB  - The association between anisotropic magnetoresistive (AMR) sensor and AC
      biosusceptometry (ACB) to evaluate gastrointestinal motility is presented. The
      AMR-ACB system was successfully characterized in a bench-top study, and in vivo
      results were compared with those obtained by means of simultaneous manometry.
      Both AMR-ACB and manometry techniques presented high temporal cross correlation
      between the two periodicals signals . The contraction frequencies using AMR-ACB
      were 73.9 +/- 7.6 mHz and using manometry were 73.8 +/- 7.9 mHz during the
      baseline . The amplitude of contraction using AMR-ACB was 396 +/- 108 MUT.s and
      using manometry were 540 +/- 198 mmHg.s during the baseline. The amplitudes of
      signals for AMR-ACB and manometric recordings were similarly increased to 86.4%
      and 89.3% by neostigmine, and also decreased to 27.2% and 21.4% by hyoscine
      butylbromide in all animals, respectively. The AMR-ACB array is nonexpensive,
      portable, and has high-spatiotemporal resolution to provide helpful information
      about gastrointestinal tract.

PMID- 22996724
TI  - Sinusoidal signal analysis of electroporation in biological cells.
AB  - Conductivity measurements in suspensions of biological cells have been used since
      many years for electroporation effectiveness evaluation. However, conductivity
      modeling by means of instantaneous values of current and voltage during pulse
      application does not take into account the effects of the sample reactance and
      the dielectric dispersion of the medium. This can lead to misinterpretation in
      the electroporation analysis. The electrical modeling and characterization of
      electroporation using sinusoidal signal analysis at 10 kHz proposed in this paper
      allows us to avoid distortions due to reactive effects of the sample. A simple
      equation establishes the relation between suspension conductivity and membrane
      conductance. This model was used in experiments with suspensions of yeast cells
      and applied electric fields of up to 450 kV/m for 1 ms. The analysis using the
      proposed model resulted in membrane conductance values of up to 8000 S/m (2) and
      allowed estimating the distribution profile of conductance on the cell membrane.

PMID- 22996726
TI  - Catalytic, mild, and selective oxyfunctionalization of linear alkanes: current
      challenges.
AB  - Selective catalysts for sustainable oxidation of alkanes are highly demanded
      because of the abundance of these molecules in the environment, the possibility
      to transform them into higher-value compounds, such as chemicals or synthetic
      fuels, and the fact that, kinetically speaking, this is a difficult reaction.
      Numerous chemical and biological catalysts have been developed in the lasts
      decades for this purpose, rendering the overview over this field of chemistry
      difficult. After giving a definition of the ideal catalyst for alkane
      oxyfunctionalization, this review aims to present the catalysts available today
      that are closest to ideal.

PMID- 22996725
TI  - Women's reflections and actions regarding working after breast cancer surgery - a
      focus group study.
AB  - BACKGROUND: To better understand processes affecting return to work (RTW) after
      breast cancer, more knowledge from the perspective of sickness absentees is
      warranted. Still, research based on women's own reasoning and actions in RTW is
      very scarce. This study aims to elucidate how women with breast cancer reflect
      and act on work-related issues. MATERIAL AND METHODS: Thematic analyses of data
      from four focus group interviews with 23 women who had had breast cancer surgery
      in the previous 3-13 months were carried out. RESULTS: The five following themes
      of reflections regarding RTW were identified: 'health and functioning', 'self
      esteem/integrity', 'value of work', 'relationships at work', and 'social
      circumstances'. These reflections were associated with the three identified
      themes of actions taken by the women: 'to work or to be sickness absent', 'to
      adjust work according to own needs or not', and 'to disclose or to hide one's
      cancer'. There was a distinct difference between women who experienced work as a
      source of well-being and those who needed a respite from work. CONCLUSION: This
      study adds knowledge to the process of RTW after breast cancer and focuses on
      factors that lead the women to an active role in this process. We point to the
      interplay between women's own preferences, perceived competence, outer
      opportunities, and the actions each woman take with regard to RTW, which need to
      be recognized by all stakeholders involved. Furthermore, it continues to be
      essential to address the specific issue of disclosure in the workplace because
      this may be distressing for women.

PMID- 22996728
TI  - Point-of-care colorimetric detection with a smartphone.
AB  - Paper-based immunoassays are becoming powerful and low-cost diagnostic tools,
      especially in resource-limited settings. Inexpensive methods for quantifying
      these assays have been shown using desktop scanners, which lack portability, and
      cameras, which suffer from the ever changing ambient light conditions. In this
      work, we introduce a novel approach of quantifying colors of colorimetric
      diagnostic assays with a smartphone that allows high accuracy measurements in a
      wide range of ambient conditions, making it a truly portable system. Instead of
      directly using the red, green, and blue (RGB) intensities of the color images
      taken by a smartphone camera, we use chromaticity values to construct calibration
      curves of analyte concentrations. We demonstrate the high accuracy of this
      approach in pH measurements with linear response ranges of 1-12. These results
      are comparable to those reported using a desktop scanner or silicon
      photodetectors. To make the approach adoptable under different lighting
      conditions, we developed a calibration technique to compensate for measurement
      errors due to variability in ambient light. This technique is applicable to a
      number of common light sources, such as sun light, fluorescent light, or
      smartphone LED light. Ultimately, the entire approach can be integrated in an
      "app" to enable one-click reading, making our smartphone based approach operable
      without any professional training or complex instrumentation.

PMID- 22996727
TI  - Growth factors from tumor microenvironment possibly promote the proliferation of
      glioblastoma-derived stem-like cells in vitro.
AB  - Glioblastoma multiform is a lethal brain glial tumor characterized by low
      survival and high recurrence, partially attributed to the glioblastoma stem cells
      according to recent researches. Microenvironment or niche in tumor tissue is
      believed to provide essential support for the aberrant growth of tumor stem
      cells. In order to explore the effect of growth factors in tumor microenvironment
      on glioblastoma stem cells behavior, glioblastoma-derived stem-like cells (GDSCs)
      were isolated from adult human glioblastoma specimen with antibody against
      surface marker CD133 and were co-cultured with various tumor cells including
      U87MG cells, unsorted glioblastoma tumor cells, CD133(-) cells and normal rat
      primary astrocytes. Results suggested that tumor cells could promote GDSCs
      proliferation while non-tumor cells could not, and several growth factors were
      exclusively detected in the co-culture system with tumor cells. It was concluded
      that growth factors derived from tumor microenvironment possibly contributed to
      the uncontrolled proliferation of GDSCs.

PMID- 22996729
TI  - Response of P. aeruginosa E(1) gene expression to cadmium stress.
AB  - Heavy metal resistance microorganism plays an important role on polluted soil
      bioremediation. To obtain further knowledge of the resistant mechanism employed
      by cadmium-resistant bacteria, some gene expression profiles at transcription
      level were investigated in P. aeruginosa E(1) subjected to cadmium stress using
      real-time PCR. Exposure to cadmium for 1 h, the expression of czcA, czcB, and
      czcC all reached the peak of up-regulation 8.82-, 4.83-, and 7.43-fold,
      respectively. The response of czcD was earlier and stronger than czcABC. CysM
      contributed to cysteine synthesis kept up-regulation within the beginning 2 h.
      The expression of mgtAE genes related to Mg(2+) influx was up-regulated all the
      while, znuB responsible for Zn(2+) transportation kept up-regulation from 30 min
      to 4 h. The result support the two cadmium-resistance mechanisms including
      effluxing and inactive the heavy metal ions. The mechanism was brought that
      increase of Mg(2+) and Zn(2+) in cytoplasm would prevent Cd(2+)-binding enzymes
      to decrease the harm to cell.

PMID- 22996730
TI  - Controlling the self-assembly of a mixed-metal Mo/V-selenite family of
      polyoxometalates.
AB  - Five mixed-metal mixed-valence Mo/V polyoxoanions, templated by the pyramidal
      SeO(3)(2-) heteroanion have been isolated:
      K(10)[Mo(VI)(12)V(V)(10)O(58)(SeO(3))(8)]?18 H(2)O (1),
      K(7)[Mo(VI)(11)V(V)(5)V(IV)(2)O(52)(SeO(3))]?31 H(2)O (2),
      (NH(4))(7)K(3)[Mo(VI)(11)V(V)(5)V(IV)(2)O(52)(SeO(3))(Mo(V)(6)V(V)-O(22))]?40
      H(2)O (3), (NH(4))(19)K(3)[Mo(VI)(20)V(V)(12)V(IV)(4)O(99)(SeO(3))(10)]?36 H(2)O
      (4) and [Na(3)(H(2)O)(5){Mo(18-x)V(x)O(52)(SeO(3))} {Mo(9
      y)V(y)O(24)(SeO(3))(4)}] (5). All five compounds were characterised by single
      crystal X-ray structure analysis, TGA, UV/Vis and FT-IR spectroscopy, redox
      titrations, and elemental and flame atomic absorption spectroscopy (FAAS)
      analysis. X-ray studies revealed two novel coordination modes for the selenite
      anion in compounds 1 and 4 showing eta,MU and MU,MU coordination motifs.
      Compounds 1 and 2 were characterised in solution by using high-resolution ESI-MS.
      The ESI-MS spectra of these compounds revealed characteristic patterns showing
      distribution envelopes corresponding to 2- and 3- anionic charge states. Also,
      the isolation of these compounds shows that it may be possible to direct the self
      assembly process of the mixed-metal systems by controlling the interplay between
      the cation "shrink-wrapping" effect, the non-conventional geometry of the
      selenite anion and fine adjustment of the experimental variables. Also a detailed
      IR spectroscopic analysis unveiled a simple way to identify the type of
      coordination mode of the selenite anions present in POM-based architectures.

PMID- 22996732
TI  - Abstracts of the 35th National Congress of the Italian Association for the Study
      of the Pancreas (AISP). Peschiera del Garda, Italy. October 13-15, 2011.

PMID- 22996731
TI  - Contributions of spinal D-amino acid oxidase to bone cancer pain.
AB  - D-Amino acid oxidase (DAAO), a FAD-dependent peroxisomal flavoenzyme that
      catalyzes oxidation of D-amino acids to hydrogen peroxide, is distributed in the
      spinal cord almost exclusively expressed within astrocytes. The present study
      aims to explore potential contributions of spinal DAAO to the development of bone
      cancer pain and morphine tolerance to analgesia. Tibia inoculation of carcinoma
      cells produced mechanical allodynia (but not heat hyperalgesia), in synchronous
      with induction of DAAO expression and DAAO enzymatic activity, as well as
      activation of spinal astrocytes marked by GFAP. Subcutaneous and intrathecal
      injection of the specific DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol)
      blocked mechanical allodynia in a dose- and time-dependent manner in tumor
      bearing rats, with maximum inhibition of 40-50 %. Multi-daily intrathecal
      injections of the DAAO gene silencer siRNA/DAAO also yielded anti-allodynic
      effects by approximately 40 % and the analgesia remained for at least 6 days.
      Subcutaneous injection of CBIO suppressed the production of spinal hydrogen
      peroxide and GFAP expression. 7-Day multiple bi-daily injections of CBIO produced
      anti-allodynia without inducing self-tolerance to analgesia or cross-tolerance to
      morphine, and concurrent injections of CBIO with morphine produced apparent
      additive anti-allodynia and completely prevented morphine tolerance in behaviors
      and spinal expression of MU-opioid receptors. Our results provide the first
      evidence that spinal DAAO contributes to the development of morphine tolerance to
      analgesia and bone cancer pain accounting for 40-50 % pain status, probably via
      production of hydrogen peroxide leading to activation of astrocytes. The unique
      characterizations of DAAO inhibitors make them a potential for the treatment of
      cancer pain when they are administered alone or in combination with morphine.

PMID- 22996733
TI  - Abstracts of the 36th National Congress of the Italian Association for the Study
      of the Pancreas (AISP). Bologna, Italy. October 4-6, 2012.

PMID- 22996734
TI  - Robust and high-resolution simulations of nonlinear electrokinetic processes in
      variable cross-section channels.
AB  - We present a model and an associated numerical scheme to simulate complex
      electrokinetic processes in channels with nonuniform cross-sectional area. We
      develop a quasi-1D model based on local cross-sectional area averaging of the
      equations describing unsteady, multispecies, electromigration-diffusion
      transport. Our approach uses techniques of lubrication theory to approximate
      electrokinetic flows in channels with arbitrary variations in cross-section; and
      we include chemical equilibrium calculations for weak electrolytes, Taylor-Aris
      type dispersion due of nonuniform bulk flow, and the effects of ionic strength on
      species mobility and on acid-base equilibrium constants. To solve the quasi-1D
      governing equations, we provide a dissipative finite volume scheme that adds
      numerical dissipation at selective locations to ensure both unconditional
      stability and high accuracy. We couple the numerical scheme with a novel adaptive
      grid refinement algorithm that further improves the accuracy of simulations by
      minimizing numerical dissipation. We benchmark our numerical scheme with existing
      numerical schemes by simulating nonlinear electrokinetic problems, including ITP
      and electromigration dispersion in CZE. Simulation results show that our approach
      yields fast, stable, and high-resolution solutions using an order of magnitude
      less grid points compared to the existing dissipative schemes. To highlight our
      model's capabilities, we demonstrate simulations that predict increase in
      detection sensitivity of ITP in converging cross-sectional area channels. We also
      show that our simulations of ITP in variable cross-sectional area channels have
      very good quantitative agreement with published experimental data.

PMID- 22996735
TI  - Selective pressure dominates the synonymous codon usage in parvoviridae.
AB  - Parvoviridae is a family of small non-enveloped viruses and divided into two
      subfamilies. The family members infect a wide range of organisms from insects to
      humans and some of the members (e.g., nonpathogenic adeno-associated viruses) are
      effective gene therapy delivery vectors. We detailed the synonymous codon usage
      pattern of Parvoviridae family from the available 58 sequenced genomes through
      multivariate statistical methods. Our results revealed that nine viruses showed
      some degree of strong codon bias, and the others possessed a general weak trend
      of codon bias. ENc-plot and neutrality plot results showed that selective
      pressure dominated over mutation in shapes coding sequence's composition. The
      overall GC content and GC content at the third synonymous codon position were the
      principal determinants behind the variations within the codon usage patterns, as
      they both significantly correlated with the first axis of correspondence
      analysis. In addition, gene length had no direct influence on the codon usage
      pattern. Densovirinae subfamily and Parvovirinae subfamily possessed nine
      identical preferred codons, though most of the two subfamilies codon usage
      frequencies were significantly different. The result of cluster analysis based on
      synonymous codon usage was discordant with that of taxonomic classification.
      Adeno-associated viruses formed a separated clade far from other Parvoviridae
      members in the dendrogram. Thus, we concluded that natural selection rather than
      mutation pressure accounts for the main factor that affects the codon bias in
      Parvoviridae family.

PMID- 22996736
TI  - Detection and molecular characterization of avipoxviruses isolated from different
      avian species in Egypt.
AB  - Six clinical cases of avipoxvirus (APV) infection were investigated and molecular
      biologically studied. The samples were collected from different domesticated
      birds reared in the Egyptian backyard management system and were propagated on
      the chorioallantoic membrane of embryonated chicken eggs. The virus isolation was
      confirmed via PCR amplification of fpv167 (P4b) gene locus. All the studied
      isolates were characterized as Fowlpox-like viruses based on the amplicon length
      of fpv140 gene locus. The phylogenetic analysis of fpv167 (P4b) gene clustered
      Elsharqyia_FWPV1, Elsharqyia_FWPV2, Elsharqyia_FWPV3, Elsharqyia_FWPV4, and
      Elsharqyia_TKPV strains within subclade A1. Furthermore, Elsharqyia_PGPV strain
      was clustered within subclade A2 (Turkeypox virus) and showed 100 % nucleic acid
      identity with the wood pigeon Indian which was isolated in 2009. On the other
      hand, when the fpv140 gene was used for the phylogenetic analysis,
      Elsharqyia_PGPV was clustered within subclade A4 (Pigeonpox virus) with the other
      PGPVs. This study is considered the first molecular record for APVs circulating
      in the Egyptian birds. Further studies in a larger scale need to be developed to
      have a better understanding about the molecular characterization of the Egyptian
      APV strains.

PMID- 22996737
TI  - Full-length genome sequence of Ntaya virus.
AB  - Presentation of pyrosequencing data and phylogenetic analysis for the full genome
      of Ntaya virus, type virus of the Ntaya virus group of the Flaviviridae isolated
      in Cameroon in 1966.

PMID- 22996738
TI  - Functional p53 determines docetaxel sensitivity in prostate cancer cells.
AB  - BACKGROUND: Docetaxel is the first line treatment for castration resistant
      prostate cancer (CRPC). However, docetaxel resistance rapidly develops.
      Identifying the critical mechanisms giving rise to docetaxel resistance is the
      major challenge in advanced prostate cancer. METHODS: The effects of docetaxel on
      human DU145, PC3, LNCaP, and C4-2 prostate cancer cells were examined in cell
      culture, and p53 expression were analyzed by Western blot analysis. The potential
      role of p53 in docetaxel sensitivity in prostate cancer cells was tested by
      either p53 silencing using shRNA or p53 overexpression by introducing wild-type
      p53. RESULTS: We found that DU145 (mutant p53) and PC3 (p53 null) cells were less
      sensitive than LNCaP and C4-2 cells expressing functional p53 in response to
      docetaxel. Docetaxel treatment induces considerably higher apoptosis in LNCaP and
      C4-2 cells than in DU145 and PC3 cells in a dose dependent manner. Docetaxel
      increases the levels of ser15 phosphorylation of p53 in a dose dependent manner
      in both LNCaP and C4-2 cells, while has no effect on the levels of ser15
      phosphorylation of p53 in DU145 cells. These results suggest that p53
      phosphorylation is associated with docetaxel sensitivity in prostate cancer
      cells. To further confirm whether p53 activation can induce cell sensitivity to
      docetaxel treatment, we used p53 shRNA to knock down p53 expression in C4-2 cells
      and determined the cells response to docetaxel treatment. Knockdown of p53
      significantly down regulated p53 phosphorylation and blocked docetaxel induced
      apoptotic cell death compared to the vector control. To further confirm this
      observation, we established a stable knock out p53 in C4-2 cells. Down regulation
      of p53 in the stable p53 knock out C4-2 cells significantly inhibited docetaxel
      induced apoptotic cell death. We also used wild-type (WT) p53 to over express p53
      in DU145 cells, and found that expression of WT-p53 in DU145 cells increased
      their sensitivity to docetaxel. CONCLUSIONS: These results demonstrate that
      docetaxel induces p53 phosphorylation and that p53 status is a crucial
      determinant of docetaxel sensitivity in prostate cancer cells.

PMID- 22996739
TI  - The prevalence of dementia in rural Tanzania: a cross-sectional community-based
      study.
AB  - OBJECTIVES: Despite the growing burden of dementia in low-income countries, there
      are few previous data on the prevalence of dementia in sub-Saharan Africa. The
      aim of this study was to estimate the prevalence of dementia in those who are 70
      years and older in the rural Hai District of Tanzania. METHODS: This was a two
      phase cross-sectional survey. Using census data, we screened individuals aged 70
      years and older from six rural villages using the Community Screening Instrument
      for Dementia in Phase I. In Phase II, a stratified sample of those identified in
      Phase I were clinically assessed using the DSM-IV criteria. RESULTS: Of 1198
      people who fulfilled the inclusion criteria, 184 screened positive for probable
      dementia, and 104 screened positive for possible dementia using the Community
      Screening Instrument for Dementia. During clinical assessment in Phase II, 78
      cases of dementia were identified according to the DSM-IV criteria. The age
      standardised prevalence of dementia was 6.4% (95% confidence interval: 4.9 to
      7.9). Prevalence rates increased significantly with increasing age. CONCLUSIONS:
      The prevalence of dementia in this rural Tanzanian population is similar to that
      reported in high-income countries. Dementia is likely to become a significant
      health burden in this population as demographic transition continues. Further
      research on risk factors for dementia in sub-Saharan Africa is needed to inform
      policy makers and plan local health services.

PMID- 22996740
TI  - Bacterial vectors for imaging and cancer gene therapy: a review.
AB  - The significant burden of resistance to conventional anticancer treatments in
      patients with advanced disease has prompted the need to explore alternative
      therapeutic strategies. The challenge for oncology researchers is to identify a
      therapy which is selective for tumors with limited toxicity to normal tissue.
      Engineered bacteria have the unique potential to overcome traditional therapies'
      limitations by specifically targeting tumors. It has been shown that bacteria are
      naturally capable of homing to tumors when systemically administered resulting in
      high levels of replication locally, either external to (non-invasive species) or
      within tumor cells (pathogens). Pre-clinical and clinical investigations
      involving bacterial vectors require relevant means of monitoring vector
      trafficking and levels over time, and development of bacterial-specific real-time
      imaging modalities are key for successful development of clinical bacterial gene
      delivery. This review discusses the currently available imaging technologies and
      the progress to date exploiting these for monitoring of bacterial gene delivery
      in vivo.

PMID- 22996741
TI  - MiR-155 inhibits the sensitivity of lung cancer cells to cisplatin via negative
      regulation of Apaf-1 expression.
AB  - MicroRNA-155 (miR-155) overexpression is often found in malignancies including
      lung cancer. The objective of this study is to verify the hypothesis, based on
      the results of bioinformatics analysis, that miR-155 modulates cellular apoptosis
      and DNA damage through the regulation of Apaf-1 and is thus involved in the
      development and progression of lung cancer. First, we measured the expression of
      miR-155 and the Apaf-1 protein in lung cancer tissues. The results showed that
      expression of miR-155 was significantly higher in lung cancer tissues than in
      paracancerous and normal tissues; whereas Apaf-1 expression was lower in the lung
      cancerous tissues. We then established miR-155-silenced and Apaf-1-overexpressed
      A549 cell lines by transfection with pMAGic2.0-BIC-siRNA and pcDNA3.1-Apaf-1,
      respectively. These cell lines were then treated with cisplatin, and apoptosis
      and DNA damage were assessed, with non-transfected A549 cells used as negative
      controls. The results showed that, relative to controls, the silencing of miR-155
      resulted in elevated expression of the Apaf-1 protein, whereas Apaf-1 mRNA levels
      remained unchanged. Both the silencing of miR-155 and the overexpression Apaf-1
      greatly increased the sensitivity of A549 cells to cisplatin treatment, as
      evidenced by elevated rates of apoptosis and DNA damage. Furthermore, dual
      transfection of A549 cells with miR-155 siRNA and Apaf-1 siRNA resulted in the
      attenuation of apoptosis and DNA damage. In conclusion, the inhibition of miR-155
      can enhance the sensitivity of A549 cells to cisplatin treatment by modulation of
      cellular apoptosis and DNA damage through an Apaf-1-mediated pathway.

PMID- 22996742
TI  - Efficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma
      in immunocompetent mice.
AB  - Replication-competent oncolytic herpes simplex viruses (HSVs) are considered a
      promising therapeutic approach for treatment of high-grade gliomas (HGGs), which
      are usually resistant to all the available treatments. We previously demonstrated
      that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth
      factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient
      NOD/SCID mice in an intracranial model of HGG. However, because the treatment is
      designed to be employed on immunocompetent patients, it is necessary to test
      whether the host immune system impairs the viral efficacy or triggers a
      potentially fatal reaction. Here we confirmed the safety of R-LM113 in the
      immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when
      intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2
      in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R
      LM113 leads to a significant improvement in animal survival when administered at
      the time of tumor inoculation, as well as when injected into an already
      established tumor. This study suggests that the host immune defenses do not
      curtail the oncolytic antitumor activity of replication-competent HSV R-LM113,
      which results effective in counteracting tumor growth.

PMID- 22996743
TI  - Impact + resistance training improves bone health and body composition in
      prematurely menopausal breast cancer survivors: a randomized controlled trial.
AB  - Our randomized controlled trial in prematurely menopausal breast cancer survivors
      showed that impact + resistance training prevented increases in percentage of
      body fat compared with controls and also improved BMD at the hip and prevented
      BMD loss at the spine among exercise-trained women who were menopausal for >1
      year. INTRODUCTION: Cancer treatment-related menopause worsens bone health and
      body composition in breast cancer survivors (BCS). We investigated whether impact
      + resistance training could improve bone mineral density (BMD), reduce bone
      turnover, build muscle, and decrease fat mass in BCS with premature menopause.
      METHODS: We conducted a randomized controlled trial in 71 BCS (mean age, 46.5
      years) within 5 years of treatment-related menopause. Women were randomly
      assigned to one of two groups: (1) impact + resistance training (prevent
      osteoporosis with impact + resistance (POWIR)) or (2) exercise placebo (FLEX)
      3*/week for 1 year. Outcomes were hip and spine BMD (in grams per square
      centimeter) and body composition (percent body fat (%BF) and lean and fat mass
      (in kilograms)) by DXA and bone turnover markers (serum osteocalcin (in nanograms
      per milliliter) and urinary deoxypryrodinoline (in nanomoles per milliliter).
      RESULTS: There were no significant group * time interactions for bone outcomes
      when using an intent-to-treat approach on the full sample. In analyses restricted
      to BCS who were menopausal for >=1 year, POWIR increased BMD at the hip and
      slowed BMD loss at the spine compared with FLEX (femoral neck-POWIR, 0.004 +/-
      0.093 g/cm(2) vs. FLEX, -0.010 +/- 0.089 g/cm(2); p < 0.01; spine-POWIR, -0.003
      +/- 0.114 g/cm(2) vs. FLEX, -0.020 +/- 0.110 g/cm(2); p = 0.03). POWIR prevented
      increases in %BF (POWIR, 0.01 % vs. FLEX, 1.3 %; p < 0.04). Women with attendance
      to POWIR at >=64 % had better improvements in %BF than women attending less often
      (p < 0.03). CONCLUSION: Impact + resistance training may effectively combat bone
      loss and worsening body composition from premature menopause in BCS.

PMID- 22996744
TI  - Magnetic particle imaging: visualization of instruments for cardiovascular
      intervention.
AB  - PURPOSE: To evaluate the feasibility of different approaches of instrument
      visualization for cardiovascular interventions guided by using magnetic particle
      imaging (MPI). MATERIALS AND METHODS: Two balloon (percutaneous transluminal
      angioplasty) catheters were used. The balloon was filled either with diluted
      superparamagnetic iron oxide (SPIO) ferucarbotran (25 mmol of iron per liter) or
      with sodium chloride. Both catheters were inserted into a vessel phantom that was
      filled oppositional to the balloon content with sodium chloride or diluted SPIO
      (25 mmol of iron per liter). In addition, the administration of a 1.4-mL bolus of
      pure SPIO (500 mmol of iron per liter) followed by 5 mL of sodium chloride
      through a SPIO-labeled balloon catheter into the sodium chloride-filled vessel
      phantom was recorded. Images were recorded by using a preclinical MPI
      demonstrator. All images were acquired by using a field of view of 3.6 * 3.6 *
      2.0 cm. RESULTS: By using MPI, both balloon catheters could be visualized with
      high temporal (21.54 msec per image) and sufficient spatial (<= 3 mm) resolution
      without any motion artifacts. The movement through the field of view, the
      inflation and deflation of the balloon, and the application of the SPIO bolus
      were visualized at a rate of 46 three-dimensional data sets per second.
      CONCLUSION: Visualization of SPIO-labeled instruments for cardiovascular
      intervention at high temporal resolution as well as monitoring the application of
      a SPIO-based tracer by using labeled instruments is feasible. Further work is
      necessary to evaluate different labeling approaches for diagnostic catheters and
      guidewires and to demonstrate their navigation in the vascular system after
      administration of contrast material. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120424/-/DC1.

PMID- 22996745
TI  - Altered brain functional connectivity in patients with cirrhosis and minimal
      hepatic encephalopathy: a functional MR imaging study.
AB  - PURPOSE: To investigate patterns of whole-brain functional connectivity in
      patients with minimal hepatic encephalopathy (HE) by using functional magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the
      local institutional review board and was HIPAA compliant. All participants
      provided written informed consent. Neuropsychiatric tests including number
      connection test type A and digit symbol test were used to define minimal HE.
      Twenty-three patients with minimal HE and 25 age- and sex-matched healthy
      volunteers were included in this study. Resting-state functional MR imaging was
      performed by using a 3-T MR imaging unit. Functional connectivities between 90
      pairs of cortical and subcortical regions in patients with minimal HE were
      compared with those in control participants, and significantly different
      connectivities were chosen as connectivities of interest (COIs). Correlations
      between neuropsychiatric tests and correlation coefficients of COIs were
      calculated. RESULTS: Among the 51 COIs that were significantly different in
      patients with minimal HE from those in control participants, 44 connectivities
      were weaker in patients with minimal HE. All 22 COIs related to subcortical
      regions of interest (bilateral putamen, pallidum, and thalamus) were weaker in
      patients with minimal HE. Of 29 cortical COIs, 22 connectivities were weaker and
      seven were stronger in patients with minimal HE. Nearly all COIs with significant
      differences correlated with digital symbol test scores (P<.05, false discovery
      rate corrected). No correlation was found among blood ammonia level, Child-Pugh
      scores, or any COIs in patients with minimal HE (P>.05, false discovery rate
      corrected). CONCLUSION: Widespread cortical and subcortical network connectivity
      changes that correlated with neuropsychologic impairment were found in patients
      with minimal HE. In particular, impairment in the basal ganglia-thalamocortical
      circuit could play an important role in mediating neurocognitive dysfunction,
      especially for psychomotor speed and attention deficits in patients with minimal
      HE.

PMID- 22996746
TI  - Hyperpolarized water as an MR imaging contrast agent: feasibility of in vivo
      imaging in a rat model.
AB  - PURPOSE: To assess the feasibility of a perfusion magnetic resonance (MR) imaging
      technique that uses Overhauser dynamic nuclear polarization (DNP) to provide
      contrast during the continuous delivery of hyperpolarized water in rats.
      MATERIALS AND METHODS: Protocols approved by the local institutional animal care
      and use committees were followed. Twelve male Wistar rats were anesthetized and
      prepared by placing injection tubing in the subcutaneous layer (n=3), peritoneum
      (n=3), aorta (n=3), or carotid artery (n=3). Water was hyperpolarized by means of
      Overhauser DNP in the 0.35-T fringe field of a 1.5-T MR imaging magnet by using a
      custom-built system to continuously deliver radical-free hyperpolarized water to
      the subject. Fast gradient-echo and spoiled gradient-recalled-echo MR imaging
      sequences were used. The signal-to-noise ratio (SNR) of the images was calculated
      and compared. RESULTS: Images showed greatly altered SNR and enhanced flow
      contrast at all injection locations. For subcutaneous and intraperitoneal
      injections, the water perfusion trajectory was observed for approximately 5
      seconds after injection. Flow through a 4.2-cm length of artery was seen during
      intra-aortic injection. The right hemisphere of the brain was seen during
      injection into the right carotid artery. Images with hyperpolarized water had
      greatly altered SNR compared with images without injection or with the injection
      of nonhyperpolarized water, with a range of 13%-27% for the carotid and 444%
      2900% for the other regions. CONCLUSION: Perfusion contrast for MR imaging can be
      obtained by continuously infusing hyperpolarized water, providing localized
      angiography or brain perfusion information in vivo for rat models.

PMID- 22996747
TI  - 19F MR imaging golden angle-based capsule tracking for intestinal transit and
      catheter tracking: initial in vivo experience.
AB  - PURPOSE: To combine fluorine 19 ((19)F) magnetic resonance (MR) imaging and
      golden angle radial acquisition and to assess the feasibility of (19)F MR imaging
      golden angle-based tracking for catheter tracking applications and simultaneous
      three-dimensional (3D) intestinal tracking of ingested (19)F-labeled capsules in
      vivo. MATERIALS AND METHODS: Approval from the local ethical committee and
      informed consent from the subject were obtained. In vitro studies were performed
      to assess (19)F MR imaging golden angle-based tracking reliability with regard to
      temporal resolution and different tracking strategies (boundary condition-free
      tracking, composite image-based tracking, and model-based tracking). In vivo
      performance of the method was investigated in one healthy volunteer on 2 days. On
      study day 1, a duodenal catheter incorporating five (19)F-labeled capsules was
      administered nasally, and its 3D movement was tracked inside the stomach and
      esophagus. On study day 2, three (19)F-labeled capsules were swallowed, and
      intestinal movement was tracked. RESULTS: Simultaneous in vivo 3D tracking of
      multiple (19)F-labeled capsules was successfully performed without incorporation
      of boundary conditions at a temporal resolution of 252 msec. Incorporation of
      boundary conditions with composite image-based tracking and model-based tracking
      increased tracking reliability and enabled temporal resolution as high as 108
      msec. CONCLUSION: Use of (19)F MR imaging golden angle-based capsule tracking
      enables in vivo tracking of (19)F-labeled capsules and catheters at high temporal
      resolution. The presented method is applicable to physioanatomic studies of the
      gastrointestinal tract and shows potential for real-time tracking in
      interventional radiology.

PMID- 22996748
TI  - Quantification of variability in breath-hold perfusion CT of hepatocellular
      carcinoma: a step toward clinical use.
AB  - PURPOSE: To assess the variability of breath-hold perfusion computed tomography
      (CT) parameters and to investigate whether these measurements are affected by a
      commercial software upgrade in patients with hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: Written informed consent was obtained from all
      participants in this institutional ethics committee-approved study. Perfusion CT
      examinations in HCC patients were prospectively analyzed by three readers. Two
      readers repeated their analysis after an interval of at least 4 weeks. Inter- and
      intraobserver agreement, as well as intersoftware agreement, were assessed with
      intraclass correlation coefficients (ICCs) and Bland-Altman limits of agreement
      (LoA), with adjustment for correlation between repeated measures. RESULTS: Ninety
      three breath-hold perfusion CT examinations were included from 23 HCC patients.
      The ICC between readers was very high (>0.91) for blood flow (BF), high (>0.84)
      for blood volume (BV), and lower (>0.30 and >0.39) for mean transit time (MTT)
      and permeability surface area product (PS), respectively, while ICC between
      readings was high (>0.80) for BF and BV, good (>0.75) for PS, and lower (>0.38)
      for MTT, irrespective of software version. By using the current software, the
      clinically relevant percentage of LoA between readers for BF were -33%; for BV, 
      39%; for MTT, 55%; and for PS, -93%. Between readings by the most expert reader,
      the clinically relevant LoA were -35% for BF,-43% for BV, 33% for MTT, and -79%
      for PS. BF, BV, and PS values were significantly higher and MTT values were
      significantly lower (P<.01) with the current software version relative to the
      previous version. CONCLUSION: With the current CT perfusion software, only
      decreases between scans of HCC lesions of more than 35% for BF and 43% for BV, or
      an increase of more than 55% for MTT, could be considered beyond the analysis
      variability. The perfusion parameters obtained with the current and previous
      software versions were not exchangeable. The results of this study are specific
      for breath-hold perfusion CT of HCC and may not apply to different acquisition
      protocols and tumors.

PMID- 22996749
TI  - Intracranial aneurysms: midterm outcome of pipeline embolization device--a
      prospective study in 143 patients with 178 aneurysms.
AB  - PURPOSE: To evaluate the midterm clinical and angiographic outcomes after
      pipeline embolization device (PED) placement for treatment of intracranial
      aneurysms. MATERIALS AND METHODS: This prospective nonrandomized multicenter
      study was approved by the review boards of all involved centers; informed consent
      was obtained. Patients (143 patients, 178 aneurysms) with unruptured saccular or
      fusiform aneurysms or recurrent aneurysms after previous treatment were included
      and observed angiographically for up to 18 months and clinically for up to 3
      years. Study endpoints included complete aneurysm occlusion; neurologic
      complications within 30 days and up to 3 years; clinical outcome of cranial nerve
      palsy after PED placement; angiographic evidence of occlusion or stenosis of
      parent artery and that of occlusion of covered side branches at 6, 12, and 18
      months; and clinical and computed tomographic evidence of perforator infarction.
      RESULTS: There were five (3.5%) cases of periprocedural death or major stroke
      (modified Rankin Scale [mRS] > 3) (95% confidence interval [CI]: 1.3%, 8.4%),
      including two posttreatment delayed ruptures, two intracerebral hemorrhages, and
      one thromboembolism. Five (3.5%) patients had minor neurologic complications
      within 30 days (mRS = 1) (95% CI: 1.3%, 8.4%), including transient ischemic
      attack (n = 2), small cerebral infarction (n = 2), and cranial nerve palsy (n =
      1). Beyond 30 days, there was one fatal intracerebral hemorrhage and one
      transient ischemic attack. Ten of 13 patients (95% CI: 46%, 93.8%) completely
      recovered from symptoms of cranial nerve palsy within a median of 3.5 months.
      Angiographic results at 18 months revealed a complete aneurysm occlusion rate of
      84% (49 of 58; 95% CI: 72.1%, 92.2%), with no cases of parent artery occlusion,
      parent artery stenosis (<50%) in three patients, and occlusion of a covered side
      branch in two cases (posterior communicating arteries). Perforator infarction did
      not occur. CONCLUSION: PED placement is a reasonably safe and effective treatment
      for intracranial aneurysms. The treatment is promising for aneurysms of
      unfavorable morphologic features, such as wide neck, large size, fusiform
      morphology, incorporation of side branches, and posttreatment recanalization, and
      should be considered a first choice for treating unruptured aneurysms and
      recurrent aneurysms after previous treatments. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120422/-/DC1.

PMID- 22996750
TI  - Evaluation of the relationship between MR estimates of blood oxygen saturation
      and hypoxia: effect of an antiangiogenic treatment on a gliosarcoma model.
AB  - PURPOSE: To assess the reproducibility of the magnetic resonance (MR) estimate of
      blood oxygen saturation (sO(2)) in the rat brain, to evaluate the relationship
      between low MR estimate of sO(2) values and tissue hypoxia in a hypoxic and
      necrotic glioscarcoma model (9L gliosarcoma cells), and to evaluate the
      capability of the MR estimate of sO(2) parameter to help identify modifications
      induced by an antiangiogenic treatment (sorafenib) in 9L gliosarcoma tumors.
      MATERIALS AND METHODS: Experiments were performed with permits from the French
      Ministry of Agriculture. Forty-eight male rats bearing a 9L gliosarcoma were
      randomized in untreated and treated (sorafenib) groups. MR blood volume fraction
      and MR estimate of sO(2) parameters were estimated 1 day before and 1, 3, 5, and
      8 days after the start of the treatment. The in vivo MR estimate of sO(2)
      measurement was correlated with the ex vivo hypoxia assessment by using
      pimonidazole staining. Paired and unpaired t tests, as well as parametric Pearson
      tests, were used for the statistical analyses. RESULTS: In healthy tissues, MR
      estimate of sO(2) measurements were comparable to literature values and were
      reproducible (mean across all animals, 68.0% +/- 6.5 [standard deviation]). In
      untreated tumors, MR estimate of sO(2) and immunohistochemical analysis yielded
      correlated fractional hypoxic-necrotic areas (R(2) = 0.81). In tumors treated
      with antiangiogenic therapy, tumor MR estimate of sO(2) was decreased with
      respect to the healthy tissue (P< .001). CONCLUSION: Results of this study
      suggest that the MR estimate of sO(2) is a reproducible estimate that could be
      used as an in vivo probe of hypoxia in brain tumors and as a sensitive reporter
      of the hypoxic effects of antiangiogenic therapies.

PMID- 22996751
TI  - beta-Amyloid induced effects on cholinergic, serotonergic, and dopaminergic
      neurons is differentially counteracted by anti-inflammatory drugs.
AB  - beta-Amyloid (Abeta) is a small peptide that plays a potent role in synaptic
      plasticity as well as forms amyloid plaques in Alzheimer's disease (AD). Recent
      studies suggest that Abeta deposition is deleterious not only in AD, but also in
      Parkinson's disease (PD) and depression. This Abeta effect is associated with
      inflammatory processes. However, further evaluation is needed to understand how
      Abeta and inflammation interact and contribute to the regulation of the
      cholinergic, serotonergic, and dopaminergic neuronal populations. The aim of the
      present study was to investigate the effects of Abeta(1-42) on cholinergic
      neurons of the nucleus basalis of Meynert (which degenerate in AD), on
      serotonergic neurons of the dorsal raphe nucleus (which play a role in
      depression), and on dopaminergic neurons of the ventral mesencephalon (which
      degenerate in PD) in rat organotypic brain slices. Furthermore, we investigated
      whether anti-inflammatory drugs (celecoxib, citalopram, cyclooxygenase-2
      inhibitor, ibuprofen, indomethacin, piclamilast) modulate or counteract Abeta
      induced effects. Two-week-old organotypic brain slices of the nucleus basalis of
      Meynert, dorsal raphe nucleus, and ventral mesencephalon were incubated with 50
      ng/ml Abeta(1-42) with or without anti-inflammatory agents for 3 days. Our
      results reveal that Abeta significantly decreased the number of choline
      acetyltransferase-positive cholinergic, tryptophan hydroxylase-positive
      serotonergic, and tyrosine hydroxylase-positive dopaminergic neurons and that
      anti-inflammatory drugs partially counteracted the Abeta-induced neuronal
      decline. This decline was not due to apoptotic processes (as evaluated by TUNEL,
      propidium iodide, caspase), oxidative stress (as measured by nitrite, catalase,
      or superoxide dismutase-2), or inflammation, but was most likely caused by a
      downregulation of these key enzymes.

PMID- 22996752
TI  - Retrospective evaluation of laboratory-based diagnostic tools for cervical
      necrotizing fasciitis.
AB  - OBJECTIVES/HYPOTHESIS: Cervical necrotizing fasciitis (CNF) is challenging to
      diagnose and associated with high morbidity and mortality. The objective of this
      study is to evaluate the utility of two laboratory-based diagnostic tools for
      distinguishing necrotizing from non-necrotizing infection when specifically
      applied to neck infection. STUDY DESIGN: Retrospective review. METHODS: We
      reviewed 17 consecutive cases of CNF and 70 cases of non-necrotizing neck
      infection (cellulitis, phlegmon, abscess) occurring at our institution over a
      10.75-year period. Cervical necrotizing fasciitis was confirmed by operative
      report documentation. Patient demographics, presenting characteristics, and
      outcomes were recorded. RESULTS: Use of white blood cell count and serum sodium
      levels to predict cervical necrotizing fasciitis had a sensitivity of 24% (95%
      confidence interval [CI], 0.078-0.502), specificity of 81% (95% CI, 0.688-0.889),
      positive predictive value of 23% (95% CI, 0.054-0.401), and negative predictive
      value of 81% (95% CI, 0.769-0.857). A Laboratory Risk Indicator for Necrotizing
      Fasciitis (LRINEC) score of >= 6 had a sensitivity of 56% (95% CI, 0.227-0.847),
      specificity of 60% (95% CI, 0.274-0.863), positive predictive value of 25% (95%
      CI, 0.072-0.433), and negative predictive value of 85% (95% CI, 0.733-0.962).
      CONCLUSIONS: Neither the LRINEC score nor the use of admission white blood cell
      count and sodium level were useful for distinguishing cervical necrotizing
      fasciitis from non-necrotizing neck infection.

PMID- 22996753
TI  - Spontaneous metastasis in congenic mice with transgenic breast cancer is
      unaffected by plasminogen gene ablation.
AB  - Plasminogen (Plg) plays a central role in tissue remodeling during ontogeny,
      development, and in pathological tissue remodeling following physical injury,
      inflammation and cancer. Plg/plasmin is, however, not critical for these
      processes, as they all occur to a varying extent in its absence, suggesting that
      there is a functional redundancy with other proteases. To explore this functional
      overlap in the transgenic MMTV-PyMT breast cancer metastasis model, we have
      combined Plg deficiency and a pharmacological metalloprotease inhibitor, which is
      known to reduce metastasis in this model, and has been shown to synergistically
      inhibit other tissue remodeling events in Plg-deficient mice. While
      metalloprotease inhibition dramatically reduced metastasis, we found no effect of
      Plg deficiency on metastasis, either independently or in combination with
      metalloprotease inhibition. We further show that Plg gene deficiency is of no
      significant consequence in this metastasis model, when analyzed in two different
      congenic strains: the FVB strain, and a F1 hybrid of the FVB and C57BL/6J
      strains. We suggest that the extensive backcrossing performed prior to our
      studies has eliminated the confounding effect of a known polymorphic metastasis
      modifier gene region located adjacent to the Plg gene.

PMID- 22996755
TI  - Redox-active ligands in catalysis.
AB  - Nature's use of redox-active moieties combined with 3d transition-metal ions is a
      powerful strategy to promote multi-electron catalytic reactions. The ability of
      these moieties to store redox equivalents aids metalloenzymes in promoting multi
      electron reactions, avoiding high-energy intermediates. In a biomimetic spirit,
      chemists have recently developed approaches relying on redox-active moieties in
      the vicinity of metal centers to catalyze challenging transformations. This
      approach enables chemists to impart noble-metal character to less toxic, and cost
      effective 3d transitional metals, such as Fe or Cu, in multi-electron catalytic
      reactions.

PMID- 22996754
TI  - Differences between depression and paranoia: the role of emotional memories,
      shame and subordination.
AB  - The present study explores how emotional memories, shame and submissive behaviour
      in adulthood are differently related to depression and paranoia, in a sample of
      255 subjects from the general community population. Results show that emotional
      memories (especially, shame traumatic memory) are significantly correlated with
      external and internal shame. Emotional memories are significantly associated with
      submissive behaviour. Both types of shame are correlated with submissive
      behaviour, particularly internal shame. Emotional memories, external and internal
      shame are linked to depressive symptoms. Emotional memories, external and
      internal shame, and submissive behaviour are significantly related to paranoia.
      Path analysis results suggested that (1) shame traumatic memory and recall of
      threat and submissiveness in childhood predicted depressive symptoms through
      external and internal shame; (2) early emotional memories of shame, threat and
      submissiveness predicted paranoid ideation both directly and indirectly, through
      external shame; and (3) emotional memories impact on paranoid ideation both
      through their effect upon external shame and also through their indirect effect
      upon submission, which in turn fully mediates the effect of internal shame upon
      paranoid ideation. These findings highlight the differences between depression
      and paranoia. In depression, it is the internalization of early experiences of
      shame, threat and submissiveness that heighten the vulnerability to depressive
      states. In paranoia, not only shame traumas and recollections of threat and
      submissiveness directly influence paranoid beliefs but also these memories
      promote external and internal shame thoughts and feelings and submissive
      defenses, which in turn increase paranoid ideation. KEY PRACTITIONER MESSAGE:
      Individuals with shame traumas, threat and submissiveness experiences in
      childhood and high levels of external and internal shame report more depressive
      symptoms. High levels of paranoid beliefs are associated with high negative
      emotional memories, external and internal shame thoughts and feelings, and
      submissive behaviour defenses. Therapy for depression needs to incorporate
      strategies that help individuals develop skills to deal with shame experiences
      and its outputs. Treatment for paranoid ideation must address external and
      internal shame, as well as emotional memories of shame, threat and submissiveness
      in childhood and development of assertive skills.

PMID- 22996756
TI  - Silicosis exposure-response in a cohort of tin miners comparing alternate
      exposure metrics.
AB  - BACKGROUND.: The detailed lung radiographic response to silica exposure has not
      been described. In estimating the exposure-response relationship in silicosis
      with statistical models, the absence of baseline (unattributable) risk can
      disable relative-rate estimation or produce widely varying estimates. This
      obstructs identification of optimum exposure metrics and invalidates comparisons
      and meta-analyses, which assume a common background rate. METHODS.: A cohort of
      3,000 Chinese tin miners with more than 1,000 cases of silicosis was analyzed for
      the period 1961-1994. Regular surveillance documented three stages of silicosis.
      To examine the exposure-response relationship, the intercept in relative-rate
      models was fixed to correspond to 1% of the observed silicosis rate. Exposure
      metrics for contributions in different time-windows were simultaneously
      evaluated, as were burden and cumulative burden metrics. RESULTS.: Silica
      exposures that most contributed to silicosis onset occurred in the period 5-10
      years prior (excess annual rate per 10 mg-year/m(3) , ER = 0.158, 95% CI = 0.125
      0.192, or 16% per year). During 10-20 year prior, the excess rate contribution
      was much smaller (ER = 0.048, 95% CI = 0.037-0.060) but larger again during 20-30
      year prior to onset (ER = 0.112, 95% CI = 0.098-0.126). For advanced silicosis,
      all time periods contributed about equally to the rate of onset. CONCLUSIONS.:
      Reliable estimates of parameters were observed, demonstrating exposure
      contributions over time. Burden metrics with different half-lives suggested some
      reversibility for silicosis onset with a half-life of 20 years. Advanced
      silicosis was best predicted with a cumulative burden metric which was consistent
      with prior observations that previously deposited silica continues to cause
      pulmonary damage.

PMID- 22996757
TI  - Synchronous, primary, diffuse, large B-cell lymphomas involving the ethmoid sinus
      and epiglottis: a rare clinical entity.
AB  - Non-Hodgkin's lymphoma (NHL) affecting the ethmoid sinus and epiglottis is
      uncommon. Furthermore, synchronous NHLs involving the ethmoid sinus and
      epiglottis are extremely rare and have not been reported previously. This article
      reports synchronous, primary, diffuse, large B-cell lymphoma (DLBCL) arising in
      the ethmoid sinus and epiglottis, which was successfully treated by
      immunochemotherapy. A careful examination of the head and neck is necessary to
      determine the existence of multiple synchronous primary tumors, because primary
      synchronous occurrence of DLBCL in the head and neck is unusual and can impact
      the prognosis adversely.

PMID- 22996758
TI  - Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome
      associated prostate alterations: an experimental study in the rabbit.
AB  - BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibitors improve benign prostatic
      hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), often associated
      with metabolic syndrome (MetS). This study investigated the effects of PDE5
      inhibition in the prostate of rabbits fed a high fat diet (HFD) for 12 weeks. HFD
      rabbits develop the most important features of human MetS (glucose intolerance,
      dyslipidemia, increased abdominal adiposity, and hypertension), along with
      hypogonadism and LUT abnormalities (prostate and bladder inflammation/tissue
      remodeling). METHODS: Gene expression was evaluated by quantitative RT-PCR.
      Prostate morphological changes and oxygenation were evaluated by
      immunohistochemistry. RESULTS: HFD prostates showed increased PDE5 expression,
      suggesting a peculiar sensitivity of prostate to the action of PDE5 inhibitors
      during MetS. Accordingly, prostate PDE5 mRNA was negatively associated to plasma
      testosterone/estradiol ratio, whose reduction characterizes MetS, and positively
      with the expression in prostate of several genes exploring pathogenetic processes
      for BPH/LUTS, such as inflammation, leukocyte infiltration, and
      fibrosis/myofibroblast activation. Most of these genes was up-regulated by HFD,
      and significantly reduced by PDE5 inhibition, through either chronic (12 weeks)
      or, at a lower extent, acute (1-week) tadalafil dosing. Tadalafil was also able
      to reduce blood pressure and visceral fat in HFD rabbits, without changing any
      other MetS parameter. Interestingly, 1-week tadalafil administration to HFD
      rabbits, significantly blunted prostate inflammation (increased CD45
      immunopositivity), fibrosis (reduced muscle/fiber ratio) and hypo-oxygenation,
      thus suggesting a potential curative effect of PDE5 inhibition on MetS-related
      prostate alterations. CONCLUSIONS: Our data provide the experimental evidences to
      support the multiple potentiality of PDE5 inhibitors as a useful therapeutic tool
      in LUTS.

PMID- 22996759
TI  - Significance of ADC value for detection and characterization of urothelial
      carcinoma of upper urinary tract using diffusion-weighted MRI.
AB  - PURPOSE: To evaluate utility of diffusion-weighted magnetic resonance imaging
      (DWI) to detect and predict the histological characteristics of upper urinary
      tract urothelial carcinomas (UTUCs). MATERIALS AND METHODS: We retrospectively
      evaluated 20 suspicious lesions from 19 patients. MRI study included conventional
      sequences and DWI with apparent diffusion coefficient (ADC) maps calculated
      between b = 0 and b = 1,000. ADC values were measured within two different
      regions of interest (ROI): a small identical ROI placed in the most restrictive
      part of the tumour and a larger ROI covering two-thirds of the mass surface. The
      mean ADC values of the tumours were compared with that of normal renal parenchyma
      using an unpaired Student's t test. Association between ADC values and
      histological features was tested using non-parametric tests. RESULTS: Overall, 18
      tumours were confirmed histologically as UTUCs. DWI failed to detect two cases of
      UTUCs (one CIS and one small tumour of 5 mm). There was no statistically
      significant difference in ADC values measured with the small or large ROI (p =
      0.134). The mean ADC value of UTUC was significantly lower than that of the
      normal renal parenchyma (p < 0.001). No statistical association was found between
      ADC values and pathological features (location, p = 0.35; grade, p = 0.98; muscle
      invasive disease, p = 0.76 and locally advanced stage, p = 0.57). CONCLUSION: DWI
      may be interesting tool for detecting UTUCs regarding the difference of ADC
      values between the tumours and surrounding healthy tissues. In regard to low
      frequency of UTUCs, the association of ADC values and histological
      characteristics need further investigations in a large prospective multi
      institutional study.

PMID- 22996760
TI  - The Urological Dyna-CT: ex vivo feasibility study of interventional cross
      sectional imaging in the endourological operation room.
AB  - BACKGROUND: Imaging of the urinary tract and its surrounding tissue still remains
      challenging, since standard imaging in the urological operation room consists of
      fluoroscopy and plain X-rays. The combination of a ceiling-mounted X-ray system
      and a new urological intervention table now allows cross-sectional imaging and 3D
      reconstruction to be performed in the endourological operation room (Urological
      Dyna-CT). MATERIALS AND METHODS: The imaging quality of the Artis Zee Ceiling
      (Siemens Medical Solutions, Erlangen, Germany) was assessed using slice images of
      an ex vivo pig kidney model prepared with artificial stones (plaster of Paris).
      We compared the image quality of three different examination protocols with this
      model. 3D reconstruction quality was illustrated by means of retrograde filling
      of one pig's urinary tract with a diluted contrast medium. RESULTS:
      Interventional stone detection and localization is possible with a 5 s low-dose
      Urological Dyna-CT. Detailed imaging of the collecting system by retrograde
      pyelography is possible with a high image quality. CONCLUSION: The combination of
      an Artis Zee((r)) Ceiling (Siemens Medical Solutions, Erlangen, Germany) with our
      newly developed urological intervention table we call the Urological Dyna-CT. In
      addition to such standard procedures as fluoroscopy or plain X-rays, cross
      sectional imaging and 3D reconstruction of the urinary tract are possible and
      provide fast and excellent urological imaging.

PMID- 22996761
TI  - Hormone therapy for radiorecurrent prostate cancer.
AB  - BACKGROUND: The management of patients who relapse after radical radiotherapy is
      a challenging problem for the multidisciplinary team. This group of men may have
      been considered ineligible or chosen not to be treated with an initial surgical
      approach as a result of high-risk features or significant comorbid conditions. It
      is important not to miss the opportunity for definitive local salvage therapies
      at this stage, and eligible patients should undergo careful restaging to
      determine their suitability for these approaches. For those men not suitable for
      local treatment, androgen deprivation therapy (ADT) remains an option. METHODS:
      Literature review of the evidence relating to the management of hormone therapy
      for radiorecurrent prostate cancer. RESULTS: Results from retrospective studies
      have shown that not all men with biochemical relapse will experience distant
      metastasis or a reduction in survival due to prostate cancer progression.
      Therefore, the timing of ADT commencement remains controversial. However, it
      would seem appropriate to offer immediate therapy to men with advanced disease or
      unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with
      more favourable risk factors and PSA kinetics may be considered for watchful
      waiting and deferred ADT to avoid or delay the associated toxicities. Patients
      with non-metastatic disease can be given the option of castration-based therapy
      or an antiandrogen such as bicalutamide which may have potential advantages in
      maintenance of sexual function, physical capacity and bone mineral density but at
      the expense of an increase in gynaecomastia and mastalgia. Recent data suggest
      the burden of toxicity from ADT may be reduced by the use of intermittent hormone
      therapy without compromising survival in this group of patients with
      radiorecurrence. CONCLUSIONS: Hormone therapy remains an option for men with
      radiorecurrent prostate cancer.

PMID- 22996763
TI  - [Pathological evaluation and grading for neoadjuvant therapy].
AB  - In Japan, the pathological grading of pre-operative neo-adjuvant therapy for
      gastric cancer is conducted based on the criterion recommended in the Japanese
      Classification of Gastric Carcinoma. This pathological grading system has been
      developed from the classic system proposed by Drs. Oboshi and Shimosao. With this
      grading system, based on chemotherapy gastric cancer specimens are to be divided
      into 4 categories based on the ratio of the remaining tumor area against the
      tumor burden, which is a different method from the RECIST guideline, commonly
      used in clinical settings. Thus, it will be important for clinicians to
      understand the basis of this pathological grading system for neoadjuvant therapy,
      and to properly use it for further treatment of cancer patients.

PMID- 22996762
TI  - Hot and steady: Elevated temperatures do not enhance muscle disuse atrophy during
      prolonged aestivation in the ectotherm Cyclorana alboguttata.
AB  - Animals that undergo prolonged dormancy experience minimal muscle disuse atrophy
      (MDA) compared to animals subjected to artificial immobilisation over shorter
      timeframes. An association between oxidative stress and MDA suggests that
      metabolic depression presumably affords dormant animals some protection against
      muscle disuse. Because aerobic metabolism is temperature sensitive, we proposed
      that MDA in dormant (aestivating) ectotherms would be enhanced at elevated
      temperatures. In the green-striped burrowing frog, Cyclorana alboguttata, the
      thermal sensitivity of skeletal muscle metabolic rate is muscle-specific. We
      proposed that the degree of atrophy experienced during aestivation would
      correlate with the thermal sensitivity of muscle metabolic rate such that muscles
      with a relatively high metabolic rate at high temperatures would experience more
      disuse atrophy. To test this hypothesis, we examined the effect of temperature
      and aestivation on the extent of MDA in two functionally different muscles: the
      M. gastrocnemius (jumping muscle) and M. iliofibularis (non-jumping muscle), in
      C. alboguttata aestivating at 24 or 30  degrees C for 6 months. We compared a
      range of morphological parameters from muscle cross-sections stained with
      succinic dehydrogenase to show that muscle-specific patterns of disuse atrophy
      were consistent with the relative rates of oxygen consumption of those muscle
      types. However, despite muscle-specific differences in thermal sensitivity of
      metabolic rate, aestivation temperature did not influence the extent of atrophy
      in either muscle. Our results suggest that the muscles of frogs aestivating at
      high temperatures are defended against additional atrophy ensuring protection of
      muscle function during long periods of immobilisation.

PMID- 22996764
TI  - [Evaluation of clinical response of head and neck cancer patients during
      induction chemotherapy and chemoradiotherapy].
AB  - Chemoradiotherapy is recognized as the treatment of choice for patients with
      unresectable locally advanced head and neck cancer, and for those with resectable
      disease who decline surgery. To improve treatment efficacy, induction
      chemotherapy has been added to chemoradiotherapy in the past decade. Imaging
      tests are conducted during a series of treatments which require as long as four
      months, and are used to modify treatment strategy. Imaging tests are particularly
      useful for helping to avoid overtreatment. Given the better specificity 18F-FDG
      PET imaging has over traditional imaging tests, the addition of 18FFDG-PET
      imaging to CT or MRI several months after the completion of chemoradiotherapy is
      useful for detecting residual disease with viable tumor cells.

PMID- 22996765
TI  - [Timing the change of chemotherapy for non-small cell lung cancer].
AB  - Lung cancer patients thus far have been given a non-treated period called
      "treatment holiday", followed by 4-6 courses of platinum-doublet. Now,
      maintenance therapy has attracted much attention after the approval of pemetrexed
      and bevacizumab. Treatments with both drugs are effective, with mild toxicity.
      However, it was not established how to apply maintenance therapy to patients.
      Maintenance therapy with pemetrexed requires the selection of patients by the
      efficacy of induction therapy(PR or SD), performance status, and the tendency of
      disease progression. In contrast, bevacizumab monotherapy should be applied to
      all patients having PR or SD, because the therapy is less toxic and no predictive
      factor has been identified. On the other hand, the efficacy of EGFR-TKI therapy
      for patients with EGFR activating mutation has been established. EGFRTKIs are key
      drugs for patients with EGFR-mutation, and are recommended as standard first-line
      therapy. I consider that chemotherapies are the second important drugs for
      prolonging patient survival. It has not been confirmed which is superior, the
      first-line therapy with EGFR-TKIs or the second line. But when EGFR-TKIs are
      administered in first-line, we should change TKIs to chemotherapy immediately
      after determination of PD on the basis of RECIST. When EGFR-TKIs are administered
      after chemotherapy in the second line or more line, continuation of EGFR-TKIs
      after PD can be accepted as long as there is no obvious exacerbation.

PMID- 22996766
TI  - [Efficacy assessments for chemotherapy and timing of changing treatment in
      gastric cancer].
AB  - In clinical study, the RECIST guideline is used for assessing the efficacy of
      gastric cancer chemotherapy, but the guideline is not always suitable for
      clinical practice. It is not necessary in clinical practice to change treatment
      according to what progressive disease is by RECIST criteria, but it is important
      to consider comprehensive assessments of efficacy for individual patients
      according to disease symptoms, physical condition, diagnostic imaging, tumor
      markers, and empirical knowledge. It is possible to continue the same treatment
      regimen for progressive disease without encountering tumor-related symptoms.
      Besides whether regimens to be able to select for next line is important factor
      for changing treatment. The second-line anticancer chemotherapy drugs for gastric
      cancer are taxane and irinotecan. However, there are few regimens for salvage
      after third-line chemotherapy. When changing treatment, it is important to use
      key drugs for gastric cancer as much as possible. Moreover, there has been little
      evidence of second-line chemotherapy for gastric cancer, and selecting treatment
      according to the patient's condition is not yet established. It is also important
      to regularly put efficacy assessments into place, and understanding the efficacy
      of anticancer drugs and patient's condition by the assessments is related to the
      best changing and selecting treatment. The standard of the efficacy assessment is
      diagnostic imaging but not tumor markers.

PMID- 22996767
TI  - [Evaluating the effectiveness and timing of modification of anti-cancer drug
      therapies for colorectal cancer].
AB  - Although treatments for unresectable colorectal cancer have made great progress
      with new anticancer agents, they are still unsatisfactory. Development of anti
      cancer therapy and its management are important in order to improve the treatment
      outcome of colorectal cancer. In the evaluation of treatment effect, obtaining a
      baseline image at the start of treatment is very important, and CT scan is
      generally performed for this purpose. In daily clinical practice, response
      evaluation criteria in solid tumors(RECIST)is usually adapted for the assessment
      of treatment outcomes. In addition, we should make decisions about continued
      therapy on the basis of both objective and symptomatic findings. Patients
      receiving palliative chemotherapy should be monitored with a CT scan every 2 to 3
      months. It is important to make a treatment strategy individually in
      consideration of adverse events, purposes of the treatment, and tumor
      progression.

PMID- 22996768
TI  - [Responses to treatment and switching tyrosine kinase inhibitors in
      gastrointestinal stromal tumor(GIST)].
AB  - GIST is driven by a gain-of-function mutation either in the KIT or PDGFRA gene.
      Atpresent , advanced and/or metastatic GIST is primarily treated by medical
      therapy of imatinib and sunitinib, both of which are re-imbursed by the
      government in Japan. Tumor responses are usually evaluated by contrast-enhanced
      CT scan with RECIST criteria, which cannot always predict patients with long SD
      showing similar prognostic effects to CR or PR. For early detection of drug
      activities, Choi's criteria with enhanced CT scan, as well as FDG-PET(or PET-CT),
      are considered to be useful. Choi's criteria also works for the early detection
      of resistance. When resistance and/or unmanagable adverse events are observed,
      early switching of drugs without any delay is recommended if there is another
      line of treatment.

PMID- 22996769
TI  - [Efficacy of erlotinib after gefitinib administration in patients with non-small
      cell lung cancer].
AB  - We retrospectively evaluated the survival benefit of dispensing erlotinib after
      gefitinib administration in patients with nonsmall cell lung cancer. Ninety
      patients treated with erlotinib in our hospital were divided into two groups: G+
      group patients who were treated with erlotinib with prior gefitinib
      administration, and G- group patients who were treated with erlotinib without
      prior gefitinib administration. Median survival time (MST) in all 90 patients was
      275 days. MST of 22 patients in the G+ group was shorter than that of 68 patients
      in G- group, but this difference was not statistically significant (283 days vs
      177 days, p=0. 329). MST in 19 patients of the G+group who were administered
      erlotinib for over 1 month was shorter than that of 49G-group patients who were
      administered erlotinib over 1 month. However, this difference was also not
      statistically significant(395 days vs 238 days, p=0. 575). Univariate analysis
      demonstrated that EGFR mutation unknown, time to progression (TTP) with gefitinib
      longer than 1 year, gefitnib administration longer than 1 year, and responder to
      gefitinib, suggest a better prognosis. Mutivariate analysis revealed that only
      TTP with gefitinib longer than 1 year was an independent prognostic factor for
      patients in the G+ group.

PMID- 22996770
TI  - [Myeloid-derived suppressor cells in patients with breast cancer].
AB  - Myeloid-derived suppressor cells (MDSC) are one of the major cell populations
      responsible for regulating immune responses. These cells have been reported to
      accumulate in the blood, lymph nodes, and tumor sites in most patients during
      tumor progression and in chronic infection. They are also reported to potently
      suppress T-cell functions. We studied MDSC in the peripheral blood mononuclear
      cells(PBMC)by flow cytometry using blood samples from 29 patients with breast
      cancer, and from 11 healthy donors. The cell level was significantly high for
      patients compared to the 11 healthy donors (5. 68+/-6. 09% vs. 0. 91+/-0. 54%).
      MDSC was significantly higher in all of the breast cancer patients (5. 68+/-6.
      09%), preoperative patients (5. 79+/-4. 92%) and recurrent disease patients (5.
      59+/-7. 28%), compared to healthy donors, but not for postoperative patients (1.
      50+/-0. 95%). Thus, MDSC was elevated in patients with breast cancer, but
      decreased to the range of healthy individuals after the removal of the tumor
      mass. However, MDSC increased again with recurrence. We also report that in 2
      cases, MDSC in the peripheral blood and pleural effusion of patients with
      metastatic breast cancer decreased after chemotherapy with gemcitabine.

PMID- 22996771
TI  - [Usefulness of antimycotic agents (itraconazole) in chemotherapy-induced
      mucositis of breast cancer patients].
AB  - Chemotherapy-induced oral mucositis is a common adverse event in breast cancer
      patients. Breakdown of the mucosal barrier predisposes the patient to bacterial,
      fungal and viral superinfection, especially candidiasis. We demonstrated the
      frequency of chemotherapy-induced oral mucositis and oral candidiasis, and the
      efficacy of antimycotic agents in breast cancer patients. We investigated 32
      patients with advanced and metastatic breast cancer who underwent chemotherapy in
      our department from March, 2009 to August, 2010. The chemotherapy regimens were
      as follows: FEC (epirubicin/5-FU/cyclophosphamide) followed by taxanes: 21, FEC:
      1, TC (docetaxel/cyclophosphamide): 7, DOC (docetaxel): 3, and CPT-11/S-1: 1.
      Patients had blood and bacteria tests of the oral cavity at the time mucositis
      symptoms appeared. We administered an antimycotic agent (itraconazole) and
      evaluated its effect on mucositis at the time mucositis symptoms appeared. 56. 3%
      of patients had chemotherapy-induced oral mucositis, and 38. 9% of the mucositis
      patients had oral candidiasis. The incidence of mucositis increased when severe
      neutropenia occurred. 92. 9% of mucositis patients were cured or improved by
      itraconazole. In conclusion, chemotherapy caused oral candidiasis in 40% of cases
      with oral mucositis, and in about 56% of breast cancer patients. The antimycotic
      agent may be useful for chemotherapy-induced oral mucositis in breast cancer
      patients.

PMID- 22996772
TI  - [A questionnaire survey about hair loss after chemotherapy for breast cancer].
AB  - Hair loss is one of the most common side effects of chemotherapies such as FEC
      and taxane, and it greatly affects quality of life. We conducted a questionnaire
      survey of breast cancer patients who were treated with adjuvant chemotherapy
      about their hair loss. Eighty-five patients participated. They all had lost their
      hair and suffered from persistent changes in their hair condition, ranging from
      thinning to curly. More than 80% of patients had worn wigs until their hair had
      grown back. Furthermore, a few patients did not remove their wigs for 2 years
      after treatment. Unfortunately, there is no prevention or medication to combat
      hair loss due to chemotherapy at present, so cumulative examinations are awaited.
      We must provide appropriate information and support to the patient.

PMID- 22996773
TI  - [Feasibility of bevacizumab for elderly patients with metastatic colorectal
      cancer].
AB  - The feasibility of treatment containing bevacizumab (BV) for elderly patients is
      not well established. We investigated the safety of treatment containing BV for
      advanced or metastatic colorectal cancer in elderly patients. From June 2008 to
      December 2010, 22 patients were treated with BV in our hospital. We classified
      them into three groups: less than 65 years (group A: 8 patients), 66-75 years
      (group B: 9 patients), and more than 76 years (group C: 5 patients). Then, we
      compared the adverse events involving BV. The patient median age was 71. 5 (range
      45-84)years old; 10 patients were treated in first-line therapy and 12 patients
      in second-line therapy or beyond. The number of patients with hypertension was
      one (12. 5%) in group A, 3 (33. 3%)in group B, and 3 (60%) in group C. Treatment
      was continued in 4 patients, and discontinued in 18. The reasons for
      discontinuing BV treatment were tumor progression in 14 patients, toxicities in 3
      patients, and degradation of performance state in one patient. BV-associated
      adverse events had a tendency to become severe with aging, and patients for whom
      BV treatment was discontinued because of toxicities were all in group C. Severe
      adverse events of rectal bleeding, cerebral hemorrhage and cerebral infarction
      were observed in three patients. These patients had risk factors for BV
      associated adverse events such as hypertension or a history of radiation therapy,
      besides the risk factor of age. It is suggested that BV-associated adverse events
      are highly frequent and severe in elderly patients. Especially in patients over
      76 years old, risk factors such as hypertension and severe adverse events were
      observed. The administration of BV for elderly patients should be considered very
      carefully.

PMID- 22996774
TI  - [Cisplatin administration for outpatients with short hydration of less than four
      hours].
AB  - BACKGROUND: The administration of cisplatin (CDDP)-containing regimens for
      outpatients has been popularized with the development of supportive care such as
      antiemetics. Currently, the number of chemotherapies available for outpatients
      has increased for many kinds of cancer, and administration with a shorter
      duration is desirable even in CDDP-containing regimens. METHODS: Between January
      2008 and October 2011, we retrospectively evaluated 22 outpatients who received B
      50mg/m2 of cisplatin with a short hydration of within 4 hours. We instructed the
      patients to drink water(1, 000mL/day) on days 2 and 3 instead of receiving a drip
      infusion. The first course of chemotherapy was usually introduced on admission,
      and subsequent courses were administered in outpatient clinics. RESULTS: Thirteen
      cases of lung cancer, eight with gastric cancer, and one with esophageal cancer,
      were retrospectively evaluated. Thirteen CDDP+S-1 regimens, four CDDP+gemcitabine
      regimens, and five other types of regimens were administered. The median dose of
      CDDP was 60mg/m2 (range, 50-75mg/m2), the median amount of drip infusion was 1,
      600 mL (range, 1, 350-2, 000mL), and the median duration of drip infusion was 4
      hours (range 3-4 hours). The decision to use antiemetics and diuretics was made
      on a case-by-case basis. The average creatinine level before the initiation of a
      CDDP-containing regimen was 0. 778+/-0. 212mg/dL, and the lebel four weeks after
      completion of the regimen was 0. 847+/-0. 200mg/dL. Among these 22 patients, 20
      completed cisplatin-containing regimens. However, cisplatin was reduced in one
      patient due to renal dysfunction, and the cisplatin regimen was interrupted in
      one patient due to intolerable nausea and vomiting. CONCLUSIONS: CDDP
      administration at doses of 50-60mg/m2 for outpatients was suggested to be safe
      with optimal patient selection, a total duration of administration of less than
      four hours, and with 2, 000 mL of hydration on day 1 and without drip infusion
      from day 2.

PMID- 22996775
TI  - [Examination of taste threshold and serum zinc level change after chemotherapy].
AB  - For cancer patients undergoing chemotherapy, there is an onset of a variety of
      adverse events related to treatment. Among the adverse events at the moment is
      taste disorder, for which there is no established effective supportive care. We
      report the measurement and study their relationship across the changes in serum
      zinc and changes in the taste of patients undergoing chemotherapy. For cancer
      patients undergoing chemotherapy, taste threshold and serum zinc levels were
      measured on the day before administration of the therapeutic anti-cancer agent,
      and after administration of anticancer drugs on day 4 and day 7. Of taste
      thresholds in the test results, the threshold was salty on day 4 and day 7 after
      administration of anticancer agents, and a significant difference was found on
      day 7 after treatment with anticancer drugs on a day prior to administration of
      anticancer agents on day 1 (p<0. 001, p=0. 007), respectively. The serum zinc
      level was measured. There was no significant difference on day 7 after
      administration of anticancer agents and anti-cancer agent before administration
      on day 1 and day 7 after administration of anticancer drugs on day 4(p<0. 001,
      p<0. 05), respectively. A negative correlation was shown between the "salt of the
      fourth day threshold" and "serum zinc levels" (r=-0. 418, p<v0. 05). From the
      results of this study, salty and low serum zinc values tended to be blunted. The
      higher the serum zinc level was, the more sensitivity there was to salty taste.

PMID- 22996776
TI  - [A case of a resected metastatic lung tumor originating from testes which was
      difficult to diagnose preoperatively].
AB  - A 26-year-old man visited our hospital because of chest pain and bloody sputum.
      Chest X-ray showed a relatively round shadow with a border that was clear and
      smooth in the right middle lung field. The result of transbronchial lung biopsy
      (TBLB) revealed adenocarcinoma. The chest and body CT scans showed no abnormality
      except for this lung nodule. No lymphadenopathy was recognized, but chest wall
      invasion was also suspected from his symptoms. Right middle and lower bilobectomy
      and chest wall resection were performed. A pathological report showed metastasis
      to the lung from embryonal carcinoma. For young male patients, it is important to
      notice testicular malignant tumors besides the primary lung cancer.

PMID- 22996777
TI  - [Long-term survival of a patient with giant liver metastatic breast cancer
      treated with trastuzumab].
AB  - We report the long-term survival of a patient with metastatic breast cancer
      treated with trastuzumab and chemoendocrine therapy. The patient was a 60-year
      old female. She underwent right mastectomy with axillary lymphadenectomy I c for
      advanced right breast cancer in 1999. In 2007, she consulted our hospital for
      treatment of recurrent giant liver metastasis. A giant liver metastasis up to 15
      cm in diameter was detected by CT upon arrival. After 4 years of trastuzumab and
      chemoendocrine therapy, she was diagnosed as in progressive remission with good
      quality of life. Breast cancer with liver metastasis often can be life
      threatening. Therefore, an optimal chemotherapy should be applied as soon as
      possible. Trastuzumab and chemoendocrine therapy showed efficacy for the
      treatment of a HER2-positive breast cancer with recurrent giant liver metastasis.

PMID- 22996778
TI  - [A resected case of complete response after treatment with S-1 for recurrent
      squamous cell carcinoma component of the breast].
AB  - A resected case of complete response after treatment with S-1 for recurrent
      squamous cell carcinoma component of the breast is presented.A 65-year-old woman
      was admitted to another hospital because of a left breast tumor. A tumor
      approximately 6 cm in diameter was palpable in the subareolar-lower (DBE) region
      of the left breast; the diagnosis was breast cancer. We performed mastectomy and
      axillary lymph node dissection. The pathological diagnosis revealed squamous cell
      carcinoma of the left breast(pT3N1M0, Stage III A). FEC chemotherapy, a standard
      chemotherapy regimen for general breast cancer, was performed as first-line
      adjuvant therapy, but was withdrawn after 1 course due to sepsis shock. Weekly
      PTX chemotherapy as second-line treatment was also withdrawn after six courses
      due to interstitial pneumonia. Few skin rashes were observed along the incision
      scar of the left breast, but biopsy revealed skin invasion by local recurrence of
      squamous cell carcinoma of the breast. Treatment with S-1 was performed for 8
      months, and she underwent resection of left skin, fat tissue, and underlying
      muscle, including the recurrent region. No residual primary carcinoma foci was
      found in the resected specimen; therefore, the pathological diagnosis revealed
      complete response for the squamous cell carcinoma component.

PMID- 22996779
TI  - [A patient with gastric small cell carcinoma who died from meningitis
      carcinomatosa after CDDP+CPT-11 chemotherapy with good response].
AB  - A-63-year-old man was admitted to our hospital because of epigastralgia. On
      gastrointestinal fiberscopy, a complete obstruction of the pylorus was found, and
      endoscopic biopsy specimens from this region revealed gastric small cell
      carcinoma. CT scans showed the primary tumor at the pylorus with many regional
      lymph node metastases invading the pancreas. We performed gastrojejunostomy,
      followed by chemotherapy with irinotecan plus cisplatin (CDDP 30mg/m2 and CPT-11
      60mg/ m2 on day 1 and 15). Three courses of treatment resulted in a marked
      reduction of both the primary tumor and regional lymph nodes. Subsequently, the
      patient underwent distal gastrectomy. Micro examination, revealed that the tumor
      had mostly changed to necrosis and fibrosis, and the pathological TNM grading was
      pT3 (SS) pN0M0, stage II A. Postoperatively, three courses of the same
      chemotherapy were performed. However, the patient died 5 months after the second
      operation, due to meningitis carcinomatosa without metastases of other organs.

PMID- 22996780
TI  - [S-1 monotherapy achieved twenty-month survival for peritoneal lavage cytology
      positive gastric cancer patient undergoing noncurative resection].
AB  - We report a gastric cancer patient with positive peritoneal lavage cytology (CY1)
      who achieved 20-month progression free survival by S-1 monotherapy. An 82-year
      old male patient who underwent distal gastrectomy with residual disease for type
      4 scirrhous gastric cancer manifesting pyloric stenosis, direct invasion to the
      pancreas, and CY1. He received S-1 monotherapy postoperatively. His ECOG
      performance status (PS) was 0. The initial treatment schedule was 100mg/day,
      twice daily for 4 weeks with a 2-week rest, repeated every 6 weeks. Grade 2
      thrombocytopenia at the end of the 5th course of treatment required
      discontinuation of one course of treatment, and subsequent treatment was
      continued with a dose reduction to 80mg/day. Afterwards, although treatment was
      temporarily postponed for 2 weeks, the dose modification enabled him to receive S
      1 for 20 months, leading to a relative dose intensity of 81%. There was no
      evidence of disease progression. The most severe adverse events were transient
      grade 3 neutropenia as well as leukocytopenia, anemia, and thrombocytopenia,
      grade 2 each, without gastrointestinal toxicities. His PS was not deteriorated.
      Although survivalrates of CY1 gastric cancer patients are still poor, our case
      suggests that S-1 monotherapy is effective against CY1, even for patients aged
      over 80, if the relative dose intensity is maintained by comprehensive patient
      management and appropriate dose modification.

PMID- 22996781
TI  - [A case of pathological complete response after chemotherapy for liver metastasis
      with subcapsular hemorrhage from gastric cancer:].
AB  - A57 years old man with gastric cancer underwent distal gastrectomy (pT3N1M0,
      pStage II B). Three months after gastric resection, he was admitted to our
      hospital because of acute right dorsal pain. Abdominal computed tomography showed
      multiple liver tumors with subcapsular hemorrhage. He was diagnosed as multiple
      liver metastases from gastric cancer. We judged liver tumors to be unresectable
      and decided to start systemic chemotherapy with S-1 and cisplatin (CDDP) because
      he was hemodynamically stable. After 8 courses of chemotherapy, the liver tumors
      were markedly reduced and judged as clinical partial response. Left hepatectomy
      and S5, S6, S7 partial hepatectomy for liver metastasis was performed.
      Histopathological examination of the resected specimen revealed no cancer cell in
      the liver, suggesting a pathologically complete response. We consider that
      systemic chemotherapy is one of the effective treatments for unresectable liver
      metastasis with subcapsular hemorrhage from gastric metastasis.

PMID- 22996782
TI  - [A case of metastatic lung cancer from colon cancer resected successfully after
      preoperative chemotherapy].
AB  - We describe a case of metastatic lung cancer from colon cancer resected
      successfully after preoperative chemotherapy. A 68-year-old male patient
      underwent low anterior resection for colon cancer in October 2004 (Stage III a),
      transcatheteric hepatic arterial embolization (TAE) for liver metastasis (S5) in
      October 2005, and partial hepatectomy (S5) in February 2006. Forty-seven months
      after surgery, lung metastases were detected. He was treated with bevacizumab
      plus FOLFOX/FOLFIRI, but the lung metastases progressed. Panitumumab plus FOLFIRI
      was performed and a partial response was obtained. Partial pulmonary resection
      was performed done in June 2011. It is necessary to add many cases to decide the
      value of prognostic factor, surgical indication and effectiveness of preoperative
      chemotherapy for lung metastasis of colorectal cancer.

PMID- 22996783
TI  - [A case of colon cancer with idiopathic thrombocytopenic purpura (ITP) which
      achieved complete remission by chemotherapy].
AB  - A 74-year-old man diagnosed with idiopathic thrombocytopenic purpura (ITP) nine
      years ago, was referred to our hospital because of cecal cancer. After the
      infusion of a high dose of gamma globulin preoperatively, iliocecal resection and
      splenectomy were performed. His blood platelet count did not increase much
      postoperatively, therefore, adjuvant chemotherapy was not performed. After one
      year, metastases of the liver, lung, and lymph node of the para aorta were
      revealed by CT. Since high-dose steroid therapy was effective temporarily, we
      decided to perform mFOLFOX chemotherapy. After that, his blood platelet count
      increased gradually to the normal range, and steroid therapy was no longer
      required. His blood platelet count remained in the normal range after changing
      the mFOLFOX chemotherapy to FOLFIRI and XELOX chemotherapy. Some studies reported
      the effect of chemotherapy on refractory ITP, but no one has reported the effect
      of chemotherapy for colon cancer refractory to ITP. We concluded that
      chemotherapy for colon cancer can be indicated for refractory ITP.

PMID- 22996784
TI  - [A case of poorly-differentiated neuroendocrine carcinoma of the ascending colon
      with multiple liver metastases successfully treated with cisplatin and
      irinotecan].
AB  - A 74-year-old woman diagnosed with poorly-differentiated neuroendocrine carcinoma
      originating from the ascending colon was referred to our hospital. She had felt
      anorexia, abdominal pains and her (ECOG) performance status was 3. Her CT scan
      showed that some abdominal lymph nodes were swelling and that there were many
      metastatic lesions occupying most of the liver. We started chemotherapy with
      cisplatin and irinotecan according to a regimen for small cell lung cancer.
      Considering her poor PS, both of the drugs were administered at 30mg/m2 twice 4
      weeks in the first course of chemotherapy. Her anorexia and abdominal pains
      immediately disappeared, and CT scan showed that all of the metastases were
      decreased in size. After 4 courses, however, some of the metastatic lesions were
      increased in size. She died 8 months after diagnosis. The tumor marker doubling
      time was 17 days.

PMID- 22996785
TI  - [A case of adenocarcinoma occurring at colostomy site 7 years after
      abdominoperineal resection for rectal cancer resected after preoperative mFOLFOX6
      chemotherapy].
AB  - A 78-year-old man had undergone abdominoperineal resection for rectal cancer in
      2003. After 7 years, he visited our hospital with complaints of turbid discharge
      from the stoma. A tumor 11 cm in diameter was shown at the site of the stoma. A
      partial resected biopsy revealed moderately-differentiated adenocarcinoma. We
      diagnosed metachronous multiple carcinoma or recurrent cancer at the colostomy
      site. After loop colostomy of the ascending colon was performed, systemic
      chemotherapy with mFOLFOX6 was performed. After 5 courses, the tumor revealed a
      significant reduction in its size. Afterwards, the stoma including the tumor and
      remaining left-side colon with adjacent abdominal wall was resected, keeping the
      surgical margin free. In the resected specimen, histological evaluation of the
      treatment with chemotherapy was assessed to be Grade 1a. As a result of
      preoperative chemotherapy, we finally were able to resect the minimal area of the
      adjacent skin and abdominal wall, and succeed in primary closure of the surgical
      wound. This case suggests that preoperative chemotherapy is a good option for
      treating cancer occurring at a colostomy site.

PMID- 22996786
TI  - [A case report of S-1 monotherapy for advanced hepatocellular carcinoma].
AB  - We describe our experience with a patient who had advanced hepatocellular
      carcinoma (HCC) that responded markedly to treatment with the oral
      fluoropyrimidine anticancer drug S-1 (120mg/day/body bid on day 1 through 28
      followed by a 14-day recovery period). The patient was enrolled in a phase I / II
      study designed to evaluate the safety and efficacy of S-1 in patients with
      advanced HCC. The best overall efficacy was confirmed to be a partial response
      (PR). After a total of 6 courses of treatment given on an outpatient basis, the
      target lesion volume decreased by 73. 8%. With regard to adverse events, the
      patient did not develop Grade 3 or higher adverse drug reactions. Therefore, the
      patient continued outpatient treatment for a total of 6 courses. The duration of
      survival from the start of treatment until death was 820 days, suggesting that S
      1 is moderately effective and well tolerated in patients with advanced HCC.

PMID- 22996787
TI  - [A case of large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix
      successfully treated by postoperative CPT-11+CDDP chemotherapy after non-curative
      surgery].
AB  - A 31-year-old woman, gravida 3 para 3, visited a local clinic because of post
      coital bleeding. She was diagnosed as having a uterine-cervical tumor and was
      referred to our hospital. Large cell neuroendocrine carcinoma (LCNEC) of the
      uterine cervix was pathologically shown by biopsy. The patient was initially
      treated by radical hysterectomy. Postoperative pathological examination revealed
      a direct invasion to the parametrium and the positive resection margin.
      Postoperatively, she was treated by CPT-11+CDDP. One course of treatment was
      60mg/m2 of CPT-11 administered on day 1, 8 and 15, and 60 mg/m2 of CDDP on day 1,
      with an intermission after administration for 7 days. Six courses were carried
      out. This treatment resulted in complete remission. A follow-up at the outpatient
      clinic revealed the patient had been tumor-free for one year and three months
      after the first treatment. We suggest that postoperative chemotherapy with CPT
      11+CDDP might be useful in the treatment of patients with LCNEC of the uterine
      cervix.

PMID- 22996788
TI  - [A case of paclitaxel-induced peripheral neuropathy successfully treated with
      pregabalin].
AB  - Were port a 51-year-old male left renal pelvic cancer patient with paclitaxel
      (PTX)-induced peripheral neuropathy, which was successfully treated with
      pregabalin. From June 2010, a gemcitabine/PTX (GP) regimen was used as third-line
      treatment. In order to relieve the PTX-induced peripheral neuropathy, pregabalin
      (75mg/day, at night) was administered from day 6 of the 16th course. Moreover,
      pregabalin was increased to 150mg/day from day 12 of the course. Sensory
      neurotoxicity after the administration of pregabalin was decreased from CTCAE
      (version 4. 0) grade 3 to 1 at day 19 of the course. Therefore, there is a
      possibility that the PTX -induced peripheral neuropathy may be improved by
      pregabalin administration. Further trials may be needed to confirm the value of
      pregabalin.

PMID- 22996789
TI  - Applicability of the MoCA-S test in populations with little education in
      Colombia.
AB  - OBJECTIVES: The objectives of this study were to report on the use of the Spanish
      version of the Montreal Cognitive Assessment (MoCA-S) as cognitive screening tool
      in a population aged 65 to 74 years in the Andes Mountains of Colombia, assessing
      the influence of education, and to examine its test-retest reliability. METHODS:
      We performed a cross-sectional study of 150 subjects aged 65 to 74 years
      recruited from older community social centers in Manizales, Colombia. The Leganes
      Cognitive Test (LCT), a cognitive screening test for populations with low
      education, was used to exclude those who were likely to have dementia. The
      associations between the MoCA total score and cognitive domains and education
      were examined in the total sample and in those likely free of dementia. MoCA-S
      test-retest reliability was estimated by the intraclass correlation coefficient
      (ICC) between two measurements taken 7 days apart. RESULTS: Participants had low
      levels of formal education (mean years of schooling, 4.8). According to the LCT,
      the proportion of people screening positive for dementia was 16% (n = 24). The
      mean MoCA-S scores were 16.1/30 among illiterate subjects, 18.2/30 among those
      with incomplete primary school, and 20.3/30 among those with complete primary
      school (p < 0.001). Errors were frequent in the cube and clock drawing, attention
      serial subtraction, verbal fluency, and abstraction. Test-retest reliability was
      high, ICC = 0.86, 95% CI (0.76-0.93). CONCLUSION: The MoCA-S has high reliability
      in low-educated older Colombians, but scores were strongly dependent on years of
      education. Social and cultural factors must be considered when interpreting MoCA
      S given the high error rates on items that depend on the ability to read and
      write and on culture.

PMID- 22996790
TI  - Risk factors and prognosis of pulmonary complications after endoscopic submucosal
      dissection for gastric neoplasia.
AB  - BACKGROUND: Hospital-acquired pneumonia after an endoscopic submucosal dissection
      (ESD) can prolong the patient's stay in the hospital, leading to greater
      healthcare costs. However, little is known of the characteristics and risk
      factors associated with this complication. AIMS: To analyze the clinical features
      of pneumonia after ESD and to suggest a treatment plan. METHODS: This was a
      retrospective study in which the cases of 1,661 consecutive patients who
      underwent ESD for 1,725 lesions between January 2008 and June 2011 were reviewed.
      RESULTS: Of the 1,661 patients who underwent ESD during the study period, 38 were
      subsequently diagnosed with pneumonia, and an additional 18 patients exhibited
      lung consolidation, based on chest radiography, without respiratory signs or
      symptoms. The remaining 1,605 patients showed neither lung consolidation on chest
      radiography nor respiratory signs/symptoms. Continuous propofol infusion with
      intermittent or continuous administration of an opioid [odds ratio (OR) 4.498, 95
      % confidence interval (CI) 2.267-8.923], a procedure time of >2 h (OR 2.900, 95 %
      CI 1.307-6.439), male gender (OR 2.835, 95 % CI 1.164-6.909), and age >75 years
      (OR 2.765, 95 % CI 1.224-6.249) were independent risk factors for pneumonia after
      ESD. In patients with only lung consolidation (without respiratory signs and
      symptoms), the length of hospital stay and prognosis were not affected by
      antibiotics use. CONCLUSIONS: Deep sedation under continuous propofol infusion
      with opioid injection during ESD may be a risk factor for pneumonia.

PMID- 22996791
TI  - Establishing a diagnosis in indeterminate pancreaticobiliary strictures: is
      confocal laser endomicroscopy the answer?

PMID- 22996792
TI  - Epstein-barr virus-associated gastritis: a case report.

PMID- 22996793
TI  - External awareness and GABA--a multimodal imaging study combining fMRI and
      [18F]flumazenil-PET.
AB  - Awareness is an essential feature of the human mind that can be directed
      internally, that is, toward our self, or externally, that is, toward the
      environment. The combination of internal and external information is crucial to
      constitute our sense of self. Although the underlying neuronal networks, the so
      called intrinsic and extrinsic systems, have been well-defined, the associated
      biochemical mechanisms still remain unclear. We used a well-established
      functional magnetic resonance imaging (fMRI) paradigm for internal (heartbeat
      counting) and external (tone counting) awareness and combined this technique with
      [(18)F]FMZ-PET imaging in the same healthy subjects. Focusing on cortical midline
      regions, the results showed that both stimuli types induce negative BOLD
      responses in the mPFC and the precuneus. Carefully controlling for structured
      noise in fMRI data, these results were also confirmed in an independent data
      sample using the same paradigm. Moreover, the degree of the GABAA receptor
      binding potential within these regions was correlated with the neuronal activity
      changes associated with external, rather than internal awareness when compared to
      fixation. These data support evidence that the inhibitory neurotransmitter GABA
      is an influencing factor in the differential processing of internally and
      externally guided awareness. This in turn has implications for our understanding
      of the biochemical mechanisms underlying awareness in general and its potential
      impact on psychiatric disorders.

PMID- 22996794
TI  - Assessment of a wireless headband for automatic sleep scoring.
AB  - PURPOSE: Classically, professional assessment of sleep is done in the sleep
      laboratory using whole-night polysomnography (PSG). However, given a misbalance
      between accredited sleep laboratories and the large amount of patients suffering
      from sleep disorders, only few receive appropriate diagnostic assessment.
      Recently, some low-cost home sleep scoring systems have been proposed, yet such
      systems are rarely tested scientifically. The aim of the present study was to
      evaluate the staging accuracy of the home sleep scoring system Zeo (Newton, MA,
      USA). METHODS: A final sample of 21 nights from ten subjects (aged 23-45) was
      digitally recorded with PSG as well as with the Zeo system. We compared scorings
      of Zeo (on an epoch-be-epoch basis) with the Somnolyzer 24 * 7 (an automatic
      staging algorithm), expert scorers as well as the freeware SleepExplorer.
      RESULTS: It was revealed that Zeo shows moderate overall agreement as compared to
      our study standard Somnolyzer 24 * 7 (kappa = 0.56). The most obvious performance
      difference between Zeo and both other scoring approaches was stage wake (sleep
      onset latency + wake after sleep onset). While Zeo detected only 40.8 % of the
      study standard wake epochs, 70.1 % were detected by the expert scorers and 83.4 %
      by the SleepExplorer, respectively. CONCLUSIONS: Data suggest that the Zeo system
      produces acceptable sleep scoring for stage REM, light and deep sleep, with a
      specific weakness in correctly detecting waking periods.

PMID- 22996795
TI  - Synthesis of end-functionalized polyacetylenes that contain polar groups by
      employing well-defined palladium catalysts.
AB  - A series of [(dppf)PdBr(R)]-type complexes (dppf=1,1'
      bis(diphenylphosphino)ferrocene; R=p-cyanophenyl (1 a), o-hydroxymethylphenyl (1
      b), and triphenylvinyl (1 c)), in combination with silver
      trifluoromethanesulfonate (AgOTf), were demonstrated to be active for the
      polymerization of monosubstituted polar acetylene monomers HC=CCONHC(4)H(9) (2),
      HC=CCO(2)C(8)H(17) (3), HC=CCH(2)OCONHC(6)H(13) (4), HC=CCH(2)OCO(2)C(6)H(13)
      (5), and HC=CCH(CH(3))OH (6). The yields and molecular weights of the polymers
      depended on the combination of the Pd catalyst and monomer that was employed.
      Matrix-assisted laser-desorption/ionization-time of flight (MALDI-TOF) mass
      spectrometric analysis indicated the formation of polymers that contained the "R"
      and "H" groups at the chain ends. IR spectroscopic analysis supported the R-end
      functionalization of the polymers. NMR spectroscopy and MS identified the
      presence of species that were formed by single, double, and triple insertion of
      the monomers into the Pd-C(6)H(4)-p-CN bond, thereby giving solid evidence for an
      insertion mechanism for the present system. Density functional theory (DFT)
      calculations suggested the preference for 1,2-insertion of the monomer compared
      to 2,1-insertion.

PMID- 22996797
TI  - How much is too much? Limit setting and sexual acting out in a digital era.
AB  - Digital media offer unique challenges to parents in terms of their efforts to
      shepherd their children through adolescence. Adolescents' ready access to the
      Internet makes limit setting and appropriate supervision of teens much more
      challenging and offers teens qualitatively different dangers and opportunities
      for acting out than previously existed. The case of a sexually acting out adopted
      teen (with a history of sexual abuse) who used the Internet as a central vehicle
      for sexual exploration is discussed, with a particular focus on the ambiguity of
      appropriate limit setting in the digital era. Implications for case planning in
      similar situations are also discussed.

PMID- 22996798
TI  - Capillary electrophoresis-laser-induced fluorescence detection of rat brain
      catecholamines with microwave-assisted derivatization.
AB  - In this study, a rapid and sensitive method is described for the catecholamines
      detection in rat brain. CE with LIF detection for the determination of FITC
      derivatized catecholamines (dopamine, epinephrine, and norepinephrine) was
      demonstrated. Conventional water bath and microwave-assisted derivatization
      methods were employed and a significant reduction in the derivatization time from
      2 h for the conventional water bath at room temperature (ca. 25 degrees C) to 2
      min for the microwave-assisted derivatization was achieved. Online sample
      concentration of field-amplified sample stacking (FASS) method was employed to
      achieve higher sensitivities (the detection limits obtained in the normal
      injection mode ranged from 2.6 to 4.5 ng L-1 and in the FASS mode ranged from 22
      to 34 pg L-1). Furthermore, this microwave-assisted derivatization CE-LIF method
      successfully determined catecholamines in rat brain with as low as 100 ng L-1
      (FASS mode) to 10 MUg L-1 (normal injection mode). This CE-LIF method provided
      better detection ability when compared to the best reports on catecholamines
      analyses.

PMID- 22996796
TI  - The microbiology of human hygiene and its impact on type 1 diabetes.
AB  - The incidence of type 1 diabetes (T1D), as with several other autoimmune diseases
      and conditions, began to notably rise in the latter half of the last century.
      Most cases of T1D are not solely attributable to genetics and therefore,
      environmental influences are proposed to account for the difference. Humans live
      today in general under much more hygienic conditions than their ancestors.
      Although human enteroviruses (HEV) have been strongly implicated as causative
      environmental agents of T1D, recent work has shown that the bacterial genera in
      the gut of diabetics compared with non-diabetics, can vary significantly. Here,
      we consider these data in light of our non-hygienic human past in order to
      discuss a possible relationship between the resident bacterial biome and acute
      infectious events by HEV, suggesting how this may have influenced T1D incidences
      in the past and the risk for developing T1D today.

PMID- 22996799
TI  - Ara h 1 structure is retained after roasting and is important for enhanced
      binding to IgE.
AB  - SCOPE: Ara h 1 from roasted peanut binds higher levels of serum immunoglobulin E
      than raw peanuts and this is likely due to the Maillard reaction. While Ara h 1
      linear IgE epitopes have been mapped, the presence and importance of structural
      epitopes is not clear. METHODS AND RESULTS: Mass spectrometry, immunoblot, ELISA,
      circular dichroism (CD), and structural analysis were used to compare structural
      and subsequent IgE-binding differences in Ara h 1 purified from raw (N) and
      roasted peanuts (R) and denatured Ara h 1 (D). Although N and R had similar CD
      spectra, the latter bound significantly more IgE. Decreased IgE binding was seen
      with the loss of secondary structure. This same IgE-binding pattern [R > N > D]
      was seen for the sera of ten peanut allergic patients. While the majority of
      linear epitopes are located on surface and structured regions of Ara h 1, our
      study shows that conformational epitopes of Ara h 1 bind better to IgE than
      linear epitopes. CONCLUSION: Enhanced IgE binding to roasted Ara h 1 could be due
      to alterations such as chemical modifications to individual amino acids or
      increased epitope exposure. IgE binding is significantly reduced with loss of
      structure.

PMID- 22996800
TI  - Depletion of Kupffer cells modulates ethanol-induced hepatocyte DNA synthesis in
      C57Bl/6 mice.
AB  - Kupffer cells (KCs) are important in hepatic homeostasis and responses to
      xenobiotics. KCs are activated on interaction with endotoxin, releasing
      cytokines, and reactive oxygen species normally associated with increased gene
      expression, cellular growth, or hepatic injury. Ethanol-induced endotoxemia is
      one means of KC activation. We propose that KC depletion attenuates the effect of
      EtOH-induced endotoxemia to impact the hepatic growth response. Hepatic DNA
      synthesis was examined in KC competent (KC+) or KC-depleted (KC-) C57BL/6 mice
      fed EtOH-containing diet in the presence or absence of polyphenol-60 antioxidant.
      KC depletion was assessed by F4/80 antigen, and DNA synthesis was assessed by 5
      bromo-2'-deoxyuridine incorporation. Tumor necrosis factor alpha (TNF-alpha)
      messenger RNA released was quantified by RT-PCR/electrophoresis. ERK1/2
      phosphorylation was evaluated by Western blotting, and Nrf2 and CYP2E1protein
      were also assayed. Apoptosis and hepatic injury were examined by the Tunnel assay
      and hepatic transaminases in serum, respectively. Hepatic transaminases in serum
      (AST and ALT) were within normal range. Over 90% of KC was depleted by clodronate
      treatment. KC depletion decreased TNF-alpha mRNA release, ERK1/2 phosphorylation,
      and hepatocyte DNA synthesis. KC depletion is associated with increased numbers
      of apoptotic cells bodies in KC- mice. Antioxidant treatment decreased DNA
      synthesis, Nrf2, and CYP2E1 protein expression in EtOH-consuming mice. Our data
      indicate that upon ethanol exposure, KC participates in hepatic DNA synthesis and
      growth responses. Collectively, these observations suggest that KC depletion
      attenuates the downstream effect of ethanol-induced endotoxemia by reduced
      cytokine and reactive oxygen species production with its concomitant effect on
      MAPK-signaling pathway on hepatocyte DNA synthesis.

PMID- 22996801
TI  - Phase I and pharmacokinetic study of IV vinflunine in cancer patients with liver
      dysfunction.
AB  - Vinflunine is a novel tubulin-targeted agent that is currently indicated as a
      monotherapy in bladder cancer patients. The recommended dose of 320 mg/m(2) is
      given as an intravenous infusion once every 3 weeks. Vinflunine is metabolized
      through CYP3A4 and mainly eliminated via the feces. A phase I trial was designed
      to explore the tolerability and pharmacokinetics of vinflunine in cancer patients
      with ranging degrees of liver dysfunction (LD). A sequential design was used for
      patient accrual, with the objective of determining the maximum tolerated dose
      (MTD) and the recommended dose (RD) of vinflunine in 3 groups of increasing LD
      levels. Vinflunine and its only active metabolite 4-O-deacetylvinflunine were
      quantified in serial whole blood samples. PK parameters were derived and compared
      between LD groups and with a reference PK database. Vinflunine and 4-O
      deacetylvinflunine PK parameters were not affected in any of the explored LD
      levels. Geometric mean values for vinflunine total clearance were 47.8, 37.5 and
      45.4 L/h in the 3 groups of increasing degrees of LD, as compared to 42.5 L/h in
      reference patients with no LD. No relationship was found between vinflunine
      clearance and the presence or absence of cirrhosis, nor was it found with the
      presence or absence of liver metastasis or with liver-related biochemical
      parameters. Based on the observed tolerability profile, the recommended doses of
      i.v. vinflunine are 320 mg/m(2), 250 mg/m(2) or 200 mg/m(2) for patients with
      increasing degrees of liver dysfunction.

PMID- 22996802
TI  - Glutamine metabolism links growth factor signaling to the regulation of
      autophagy.
AB  - Activation of the PI3K-AKT1-FOXO module by growth factors increases survival and
      stress resistance. We identified the gene encoding glutamine synthetase (GLUL,
      glutamate-ammonia ligase) as a novel transcriptional target of this signaling
      cascade. Growth factor removal increases glutamine synthetase expression and
      activity through activation of FOXO transcription factors. Surprisingly,
      increased levels of glutamine synthetase inhibit MTOR signaling by blocking its
      lysosomal translocation. Furthermore, FOXO activation induces autophagosome
      formation and autophagic flux in a glutamine synthetase-dependent manner. This
      may be important for maintaining cell survival during conditions of growth factor
      and nutrient deprivation since inhibition of autophagy induces cell death. These
      studies reveal that glutamine metabolism can play an important regulatory role in
      the regulation of autophagy by growth factor signaling. In addition, the
      induction of autophagy by FOXO-mediated glutamine synthetase expression might
      contribute to the tumor suppressive function of FOXOs.

PMID- 22996803
TI  - Regional specificity of sex effects on subcortical volumes across the lifespan in
      healthy aging.
AB  - When conceptualizing age-specific onsets and sex-specific characteristics of
      neuropsychiatric diseases in a neurobiological context, it may be crucially
      important to consider differential trajectories of aging. Here, we investigated
      effects of age, sex, and their interactions on absolute and relative volumes of
      subcortical structures with known involvement in psychiatric disorders, including
      the basal ganglia, thalamus, hippocampus, and amygdala. Structural MRI data of 76
      healthy subjects (38 males, 19-70 years) from the ICBM database were analyzed.
      Age-related absolute atrophy was generally found in the basal ganglia and
      thalamus, while in the hippocampus decline was only observed in males, and was
      generally absent in the amygdala. Disproportionate degeneration in the basal
      ganglia and thalamus, exceeding cortical decline was specific for females. When
      allowing higher-order models, a quadratic model could better describe the
      negative relation of absolute volume and age in the basal ganglia in males, and
      generally in the hippocampus and amygdala. We could show that negative age
      relations are highly specific for certain subcortical structures in either
      gender. Importantly these findings also emphasize the significant impact of
      analytical strategies when deciding for correction of subcortical volumes to the
      whole-brain decline. Specifically, in the basal ganglia disproportionate
      shrinkage in females was suggested by the relative analysis while absolute volume
      analysis rather stressed an accelerating decline in older males. Given strong
      involvement of the basal ganglia in both cognitive aging and emotional
      regulation, our findings may be crucial for studies investigating the onset and
      prevalence of dementia and depressive symptoms in male and female aging.

PMID- 22996804
TI  - Revisiting the molecular roots of a ubiquitously successful synthesis: nickel(0)
      nanoparticles by reduction of [Ni(acetylacetonate)2].
AB  - The widely used preparation of Ni(0) nanoparticles from [Ni(acac)(2)]
      (acac=acetylacetonate) and oleylamine, often considered to be a thermolysis or a
      radical reaction, was analyzed anew by using a combination of DFT modeling and
      designed mechanistic experiments. Firstly, the reaction was followed up by using
      TGA to evaluate the energy barrier of the limiting step. Secondly, all the
      byproducts were identified using NMR spectroscopy, mass spectrometry, FTIR, and X
      ray crystallography. These methods allowed us to depict both main and side
      reaction pathways. Lastly, DFT modeling was utilized to assess the validity of
      this new scheme by identifying the limiting steps and evaluating the
      corresponding energy barriers. The oleylamine was shown to reduce the
      [Ni(acac)(2)] complex not through a one-electron radical mechanism, as often
      stated, but as an hydride donor through a two-electron chemical reduction route.
      This finding has strong consequences not only for the design of further
      nanoparticles syntheses that use long-chain amine as a reactant, but also for
      advanced understanding of catalytic reactions for which these nanoparticles can
      be employed.

PMID- 22996805
TI  - Enough is indeed enough: ACGME required changes in pediatric training.

PMID- 22996806
TI  - Health belief model to predict sharps injuries among health care workers at first
      level care facilities in rural Pakistan.
AB  - BACKGROUND: We assessed the frequency and predictors of sharp injuries (SIs)
      among health care workers (HCWs) at first level care facilities (FLCF) in rural
      Pakistan. METHOD: HCWs working at public clinic (PC), privately owned licensed
      practitioners' clinic (LPC) and non-licensed practitioners' clinic(NLC) were
      interviewed on universal precautions (UPs) and constructs of health belief model
      (HBM) to assess their association with SIs through negative-binomial regression.
      RESULTS: From 365 clinics, 485 HCWs were interviewed. Overall annual rate of SIs
      was 192/100 HCWs/year; 78/100 HCWs among licensed prescribers, 191/100 HCWs among
      non-licensed prescribers, 248/100 HCWs among qualified assistants, and 321/100
      HCWs among non-qualified assistants. Increasing knowledge score about bloodborne
      pathogens (BBPs) transmission (rate-ratio (RR): 0.93; 95%CI: 0.89-0.96), fewer
      years of work experience, being a non-licensed prescriber (RR: 2.02; 95%CI: 1.36
      2.98) licensed (RR: 2.86; 9%CI: 1.81-4.51) or non-licensed assistant (RR: 2.78;
      95%CI: 1.72-4.47) compared to a licensed prescriber, perceived barriers (RR:
      1.06; 95%CI: 1.03-1.08), and compliance with UPs scores (RR: 0.93; 95%CI: 0.87
      0.97) were significant predictors of SIs. CONCLUSION: Improved knowledge about
      BBPs, compliance with UPs and reduced barriers to follow UPs could reduce SIs to
      HCWs.

PMID- 22996807
TI  - Comparison of gene expression in fresh and frozen-thawed human preimplantation
      embryos.
AB  - Identification and characterisation of differentially regulated genes in
      preimplantation human embryonic development are required to improve embryo
      quality and pregnancy rates in IVF. In this study, we examined expression of a
      number of genes known to be critical for early development and compared
      expression profiles in individual preimplantation human embryos to establish any
      differences in gene expression in fresh compared to frozen-thawed embryos used
      routinely in IVF. We analysed expression of 19 genes by cDNA amplification
      followed by quantitative real-time PCR in a panel of 44 fresh and frozen-thawed
      human preimplantation embryos. Fresh embryos were obtained from surplus early
      cleavage stage embryos and frozen-thawed embryos from cryopreserved 2PN embryos.
      Our aim was to determine differences in gene expression between fresh and frozen
      thawed human embryos, but we also identified differences in developmental
      expression patterns for particular genes. We show that overall gene expression
      among embryos of the same stage is highly variable and our results indicate that
      expression levels between groups did differ and differences in expression of
      individual genes was detected. Our results show that gene expression from frozen
      thawed embryos is more consistent when compared with fresh, suggesting that
      cryopreserved embryos may represent a reliable source for studying the molecular
      events underpinning early human embryo development.

PMID- 22996808
TI  - The role of high-dose-rate and pulsed-dose-rate brachytherapy in the management
      of recurrent or residual stomal tumor after total laryngectomy.
AB  - OBJECTIVES/HYPOTHESIS: The main purpose of the study was to assess the role and
      efficacy of high-dose-rate (HDRBT) and pulsed-dose-rate (PDRBT) brachytherapy in
      the palliative treatment of recurrent or residual stomal tumor after total
      laryngectomy. STUDY DESIGN: We aimed at presenting a series of 22 consecutive
      patients treated in the Department of Otolaryngology, Head and Neck Surgery of
      Poznan University of Medical Sciences, and in the Brachytherapy Department of
      Greater Poland Cancer Center. METHODS: In 16 patients PDRBT was used and in six
      patients HDRBT was used. In three patients, BT procedures were performed in
      combination with simultaneous chemotherapy. Two patients were additionally
      treated with interstitial hyperthermia. In 16 patients, surgical cytoreduction of
      the tumor preceded the catheters placement. In six patients, a second course of
      BT was performed due to neck metastases. All patients were regularly followed up
      within 6 months. Local control, complications, and survival were assessed.
      RESULTS: Complete and partial remissions 6 months after finishing the treatment
      were achieved in four (20%) patients, while survival rates 24 months after BT
      were estimated for 22%. Severe late complications occurred in two (9%) patients.
      CONCLUSIONS: The results of our study show that HDRBT and PDRBT are feasible in
      previously irradiated patients with recurrent or residual stomal tumor after
      total laryngectomy. They provide acceptable toxicity and good palliative effect.

PMID- 22996809
TI  - The combination of plumbagin with androgen withdrawal causes profound regression
      of prostate tumors in vivo.
AB  - BACKGROUND: Hormonal ablation is the standard treatment for disseminated androgen
      dependent prostate cancer. Although tumor growth is controlled at first, the
      tumor invariably recurs in the form of castration-resistant prostate cancer. This
      study assessed the efficacy of a new therapeutic strategy that combines
      plumbagin, a naturally occurring naphthoquinone, with androgen ablation. METHODS:
      Viewing microscopy chambers were placed in the dorsal skinfold of mice. Syngeneic
      prostate tissue was grafted within the chambers and allowed to vascularize. H2B
      GFP/PTEN-P2 prostate cancer cells were co-implanted on top of the grafted
      prostate tissue. Androgen ablation was achieved using surgical castration. Intact
      and castrated mice were administered plumbagin or sham treatment. Tumor growth,
      mitosis and apoptosis were monitored in real-time using fluorescent Intra-Vital
      Microscopy. The mechanism of action of plumbagin was explored using human and
      mouse prostate cancer cells. RESULTS: Whereas both plumbagin and castration alone
      impeded tumor growth, only the combination of plumbagin and castration caused
      profound tumor regression in vivo, mostly due to increased apoptosis of the tumor
      cells. The cytotoxicity of plumbagin was not affected by androgens in vitro,
      suggesting that microenvironmental factors not present in culture play a crucial
      role in the combination effect. Plumbagin-induced cell death was mediated, at
      least in part, by activation of ERK and was due to generation of reactive oxygen
      species, because it was abolished by the anti-oxidant N-acetyl-L-cysteine.
      CONCLUSION: Androgen deprivation in combination with plumbagin may provide a
      significant improvement over androgen deprivation alone and deserves further
      evaluation.

PMID- 22996810
TI  - Regulatory characteristics of the Vibrio vulnificus rtxHCA operon encoding a
      MARTX toxin.
AB  - Vibrio vulnificus MARTX encoded by rtxA, an open reading frame of the rtxHCA
      operon, is essential for virulence in vitro and in mice. In this study, a primer
      extension analysis revealed that transcription of the rtxHCA operon begins at a
      single site, and is under the direction of a single promoter, P( rtxHCA ). P(
      rtxHCA ) activity appeared at the beginning of growth and reached a maximum in
      mid-exponential phase. P( rtxHCA ) activity was induced by exposure to INT-407
      cells, and the membrane fraction of INT-407 cells was the most effective for the
      induction.

PMID- 22996811
TI  - Dillapiole as antileishmanial agent: discovery, cytotoxic activity and
      preliminary SAR studies of dillapiole analogues.
AB  - In this paper, the isolation of dillapiole (1) from Piper aduncum was reported as
      well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole
      (2), isodillapiole (3)], via reduction and isomerization reactions. Also, the
      compounds' molecular properties (structural, electronic, hydrophobic, and steric)
      were calculated and investigated to establish some preliminary structure-activity
      relationships (SAR). Compounds were evaluated for in vitro antileishmanial
      activity and cytotoxic effects on fibroblast cells. Compound 1 presented
      inhibitory activity against Leishmania amazonensis (IC(50)  = 69.3 uM) and
      Leishmania brasiliensis (IC(50)  = 59.4 uM) and induced cytotoxic effects on
      fibroblast cells mainly in high concentrations. Compounds 2 (IC(50)  = 99.9 uM
      for L. amazonensis and IC(50)  = 90.5 uM for L. braziliensis) and 3 (IC(50)  =
      122.9 uM for L. amazonensis and IC(50)  = 109.8 uM for L. brasiliensis) were less
      active than dillapiole (1). Regarding the molecular properties, the
      conformational arrangement of the side chain, electronic features, and the
      hydrophilic/hydrophobic balance seem to be relevant for explaining the
      antileishmanial activity of dillapiole and its analogues.

PMID- 22996812
TI  - From sentinel cells to inflammatory culprits: cancer-associated fibroblasts in
      tumour-related inflammation.
AB  - Inflammation is now established as a hallmark of cancer. Cancer-associated
      fibroblasts (CAFs) have been established as a key component of the crosstalk
      between tumour cells and their microenvironment. Central to the role of CAFs in
      facilitating tumour growth, invasion, and metastasis is their ability to
      orchestrate tumour-related inflammation. CAFs and their soluble mediators provide
      multiple complex regulatory signals that modulate the trafficking,
      differentiation status, and function of inflammatory cells in the tumour
      microenvironment. This review focuses on pathways by which CAFs mediate tumour
      promoting inflammation and modify the components of the inflammatory
      microenvironment that facilitate tumour initiation, progression, and metastasis.

PMID- 22996813
TI  - Different analgesic effects of adenosine between postoperative and neuropathic
      pain.
AB  - BACKGROUND: Adenosine is an endogenous neuromodulator in both the peripheral and
      central nervous systems. Adenosine inhibits pain signals by hyperpolarizing
      neuronal membrane. METHODS: To clarify the effects of adenosine on pain signals,
      we tested intrathecal adenosine injection in two neuropathic pains (spinal cord
      compression and chronic constriction of sciatic nerve) and postoperative pain
      (plantar incision). RESULTS: In all three kinds of pain models, significant
      shortening of withdrawal latencies to thermal stimulation were detected from 24 h
      to 1 week after the surgery. Significant improvements of pain sensation were
      observed in all three models after intrathecal injection of Cl-adenosine 24 h
      after surgery. At 72 h after surgery, intrathecal Cl-adenosine injection
      inhibited hyperalgesia in the two neuropathic pain models but not in the
      postoperative pain model. Adenosine A1R messenger RNA (mRNA) expression
      significantly decreased in the plantar incision model. Adenosine A1R protein
      levels also decreased compared with the other two models and normal control.
      CONCLUSIONS: These results suggest that adenosine effectively inhibits pain
      signals in neuropathic pain but is less effective in postoperative pain because
      of the decrease in adenosine A1 receptors.

PMID- 22996815
TI  - Flexion contractures of the legs as the manifestation of secondary adrenal
      insufficiency due to Sheehan's syndrome.

PMID- 22996814
TI  - Isolation and characterization of endothelial cells from intramuscular
      hemangioma.
AB  - BACKGROUND: Intramuscular hemangiomas (IMHs) are benign vascular tumors of deep
      soft tissue characterized by endothelial cell (EC) proliferation. The purpose of
      this study was to isolate ECs from IMH, characterize their angiogenic phenotype
      and functional characteristics, and search for a possible signaling pathway
      related to IMH development. METHODS: EC Isolation from IMH was performed by
      digestion, filtration, washing, incubation, and purification in sequence. Tie2
      expression was compared between ECs from IMH and controls using reverse
      transcriptase polymerase chain reaction (RT-PCR). Cell invasion and proliferation
      assays were used to analyze functional responses of ECs to angiopoietin 1 (Ang1)
      and vascular endothelial growth factor (VEGF). Expression of downstream targets
      was analyzed using Western blot analysis. RESULTS: Isolated ECs showed typical
      cobblestone appearance under light microscopy and formed capillary-like tubular
      structures using Matrigel tube-forming assay. RT-PCR of isolated ECs from six
      patients showed increased expression of Tie2 and VEGF receptor 1 (VEGFR1)
      compared with control ECs. Tie2 activation by Ang1 compared with VEGFR1 by VEGF
      resulted in increased EC migration and proliferation. Western blot analysis
      showed increased Tie2 expression in hemangioma samples compared with normal ECs.
      Phosphorylated Akt and phosphorylated forkhead box O1 (FOXO1) expression was
      observed in hemangioma samples only. CONCLUSION: EC isolation from IMH could be a
      useful tool for further research. These results suggest that increased Tie2
      expression, via Akt-FOXO1 pathway activation, may play an important role in IMH
      pathogenesis.

PMID- 22996816
TI  - Metal-bis(2-picolyl)amine complexes as state 1(T) inhibitors of activated Ras
      protein.
AB  - Allosteric interactions: Metal(II) cyclens inhibit Ras-effector interactions by
      stabilizing a weak effector-binding state of Ras, state 1(T), and binding
      directly in the active site. The novel state (1T) inhibitor Zn(2+)-BPA (BPA =
      bis(2-picolyl)amine) binds outside the nucleotide binding pocket but nevertheless
      allosterically stabilizes state 1(T) and thus inhibits the Ras-Raf interaction.

PMID- 22996817
TI  - Analysis of short-chain aliphatic amines in food and water samples using a near
      infrared cyanine 1-(epsilon-succinimydyl-hexanoate)-1'-methyl-3,3,3',3'
      tetramethyl-indocarbocyanine-5,5'-disulfonate potassium with CE-LIF detection.
AB  - Precolumn derivatization of six short-chain aliphatic amines by a near-infrared
      dye, 1-(epsilon-succinimydyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl
      indocarbocyanine-5,5'- disulfonate potassium (MeCy5-OSu), followed by MEKC-CE-LIF
      detection has been developed as a method for the determination of aliphatic
      amines in environmental water and food. Optimum derivatization was operated
      nicely in pH 9.0 borate buffer at 20 degrees C for 30 min. Well separated peaks
      were observed with a pH 9.5 BGE containing 10 mmol L-1 phosphoric acid, 20 mmol L
      1 SDS, and 7% methanol buffered with 1.0 mol L-1 NaOH. The separation procedure
      was rapidly achieved within 11 min and the matrix interferences could be
      effectively eliminated. A linear calibration graph was obtained for 5-200 nmol L
      1 analytes with a correlation coefficient in the range 0.9933-0.9995 for amines.
      This method was successfully utilized to determine aliphatic amines in lake,
      sewage water, and red wine with recoveries ranging from 96.4 to 105% and the RSDs
      ranging from 0.9 to 2.9%. Near-infrared, LIF-detector-compatible MeCy5-OSu was
      proved suitable for the accurate, sensitive, and rapid separation and
      determination of aliphatic amines in water and food samples.

PMID- 22996818
TI  - Mortality due to haematological cancer in cities close to petroleum refineries in
      Spain.
AB  - Controversy exists as to whether working or living in the vicinity of a petroleum
      refinery (RF) increases the risk of haematological cancer (HC). The European
      Pollutant Release and Transfer Register obliges petroleum refineries to notify
      their emissions of toxic substances which include carcinogenic substances. Our
      objective is to determine if living in the proximity of an RF is associated with
      a greater risk of mortality due to HC in the census tracts (CTs) of the Spanish
      cities of Bilbao, Cartagena, Castellon, La Coruna, Huelva, and Santa Cruz de
      Tenerife. This is an ecological study of mortality in the years 1996-2007 which
      includes 968 CTs with 1,263,371 inhabitants. Exposure has been measured as the
      distance from the centroid of each CT to the RF. The Besag-York-Mollie
      autoregressive spatial model has been fitted by R-INLA to estimate the relative
      risk (RR) and 95 % credible intervals (95 % CrI) for distance in quintiles. The
      most distant quintile has been taken as the reference. A total of 2,574 persons
      died of HC. The distances from the CTs to RFs ranged from 0.5 to 22.5 km (median
      = 7.6 km). All of the RRs for the quintiles of distances in Huelva were greater
      than 1. Statistically significant excess risk was shown in Cartagena in the
      nearest CT (1.8 to 6.8 km; RR = 1.43, 95 % CrI 1.02 to 2.02). Radial effects have
      not been detected between the CT of residence and the petroleum RF in mortality
      due to HC in any of the cities.

PMID- 22996819
TI  - Batch and continuous biodegradation of Amaranth in plain distilled water by P.
      aeruginosa BCH and toxicological scrutiny using oxidative stress studies.
AB  - Bacterium Pseudomonas aeruginosa BCH was able to degrade naphthylaminesulfonic
      azo dye Amaranth in plain distilled water within 6 h at 50 mg l(-1) dye
      concentration. Studies were carried out to find the optimum physical conditions
      and which came out to be pH 7 and temperature 30  degrees C. Amaranth could also
      be decolorized at concentration 500 mg l(-1). Presence of Zn and Hg ions could
      strongly slow down the decolorization process, whereas decolorization progressed
      rapidly in presence of Mn. Decolorization rate was increased with increasing cell
      mass. Induction in intracellular and extracellular activities of tyrosinase and
      NADH-DCIP reductase along with intracellular laccase and veratryl alcohol oxidase
      indicated their co-ordinate action during dye biodegradation. Up-flow bioreactor
      studies with alginate immobilized cells proved the capability of strain to
      degrade Amaranth in continuous process at 20 ml h(-1) flow rate. Various
      analytical studies viz.--HPLC, HPTLC, and FTIR gave the confirmation that
      decolorization was due to biodegradation. From GC-MS analysis, various
      metabolites were detected, and possible degradation pathway was predicted.
      Toxicity studies carried out with Allium cepa L. through the assessment of
      various antioxidant enzymes viz. sulphur oxide dismutase, guaiacol peroxidase,
      and catalase along with estimation of lipid peroxidation and protein oxidation
      levels conclusively demonstrated that oxidative stress was generated by Amaranth.

PMID- 22996820
TI  - Integrated chemical species analysis with source-receptor modeling results to
      characterize the effects of terrain and monsoon on ambient aerosols in a basin.
AB  - This study integrated estimated oxidation ratio of sulfur (SOR) and oxidation
      ratio of nitrogen (NOR) with source-receptor modeling results to identify the
      effects of terrain and monsoons on ambient aerosols in an urban area (north
      basin) and a rural area (south basin) of the Taichung Basin. The estimated
      results indicate that the conversion of sulfur mainly occurs in fine particles
      (PM2.5), whereas the conversion of nitrogen occurs in approximately equal
      quantities of PM2.5 and coarse particles (PM2.5-10). The results show a direct
      relationship for PM2.5 between the modeling results with SOR and NOR. The high
      PM2.5 SOR, NOR, and secondary aerosol values all occurred in the upwind area
      during both monsoons; this shows that the photochemical reaction and the terrain
      effect on the pollutant transmission were significant in the basin. Additionally,
      the urban heat island effect on the urban area and the valley effect on the rural
      area were significant. The results show that secondary aerosol in PM2.5-10
      contributed approximately 10 % during both monsoons, and the difference in the
      contribution from secondary aerosol between both areas was small. Vehicle exhaust
      emissions and wind-borne dust were two crucial PM2.5-10 contributors during both
      monsoons; their average contributions in both areas were higher than 34 and 32 %,
      respectively.

PMID- 22996821
TI  - Comparative performance evaluation of Aspergillus lentulus for dye removal
      through bioaccumulation and biosorption.
AB  - Dyes used in various industries are discharged into the environment and pose
      major environmental concern. In the present study, fungal isolate Aspergillus
      lentulus was utilized for the treatment of various dyes, dye mixtures and dye
      containing effluent in dual modes, bioaccumulation (employing growing biomass)
      and biosorption (employing pre-cultivated biomass). The effect of dye toxicity on
      the growth of the fungal isolate was studied through phase contrast and scanning
      electron microscopy. Dye biosorption was studied using first and second-order
      kinetic models. Effects of factors influencing adsorption and isotherm studies
      were also conducted. During bioaccumulation, good removal was obtained for
      anionic dyes (100 mg/l), viz. Acid Navy Blue, Fast Red A and Orange-HF dye (99.4
      %, 98.8 % and 98.7 %, respectively) in 48 h. Cationic dyes (10 mg/l), viz.
      Rhodamine B and Methylene Blue, had low removal efficiency (80.3 % [48 h] and
      92.7 % [144 h], respectively) as compared to anionic dyes. In addition to this,
      fungal isolate showed toxicity response towards Methylene Blue by producing
      larger aggregates of fungal pellets. To overcome the limitations of
      bioaccumulation, dye removal in biosorption mode was studied. In this mode,
      significant removal was observed for anionic (96.7-94.3 %) and cationic (35.4
      90.9 %) dyes in 24 h. The removal of three anionic dyes and Rhodamine B followed
      first-order kinetic model whereas removal of Methylene Blue followed second-order
      kinetic model. Overall, fungal isolate could remove more than 90 % dye from
      different dye mixtures in bioaccumulation mode and more than 70 % dye in
      biosorption mode. Moreover, significant color removal from handmade paper unit
      effluent in bioaccumulation mode (86.4 %) as well as in biosorption mode (77.1 %)
      was obtained within 24 h. This study validates the potential of fungal isolate,
      A. lentulus, to be used as the primary organism for treating dye containing
      wastewater.

PMID- 22996822
TI  - Concentrations of asbestos fibers and metals in drinking water caused by natural
      crocidolite asbestos in the soil from a rural area.
AB  - Asbestos fibers and metals in drinking water are of significant importance to the
      field of asbestos toxicology. However, little is known about asbestos fibers and
      metals in drinking water caused by naturally occurring asbestos. Therefore,
      concentrations of asbestos fibers and metals in well and surface waters from
      asbestos and control areas were measured by scanning electron microscopy (SEM),
      inductively coupled plasma (ICP) optical emission spectrometer, and ICP-mass
      spectrometry in this study. The results indicated that the mean concentration of
      asbestos fibers was 42.34 millions of fibers per liter by SEM, which was much
      higher than the permission exposure level. The main compositions of both asbestos
      fibers in crocidolite mineral and in drinking water were Na, Mg, Fe, and Si based
      on energy dispersive X-ray analysis. This revealed that the drinking water has
      been contaminated by asbestos fibers from crocidolite mineral in soil and rock.
      Except for Cr, Pb, Zn, and Mn, the mean concentrations of Ni, Na, Mg, K, Fe, Ca,
      and SiO2 were much higher in both surface water and well waters from the asbestos
      area than in well water from the control area. The results of principal component
      and cluster analyses indicated that the metals in surface and well waters from
      the asbestos area were significantly influenced by crocidolite mineral in soil
      and rock. In the asbestos area, the mean concentrations of asbestos fibers and
      Ni, Na, Mg, K, Fe, Ca, and SiO2 were higher in surface and well waters,
      indicating that asbestos fibers and the metals were significantly influenced by
      crocidolite in soil and rock.

PMID- 22996823
TI  - Evaluating the ecological integrity of Atlantic forest remnants by using rapid
      ecological assessment.
AB  - The need for quick identification of priority areas for biodiversity protection
      makes rapid assessment methods important management tools for defining
      conservation strategies. An increasingly used rapid assessment method is rapid
      ecological assessment (REA), a fast and flexible survey directed toward selected
      indicator species and vegetation forms. The purpose of this study was to propose
      and test REA based on plant community features of the semideciduous Atlantic
      forest (SAF). Correlation tests were performed between data collected by REA and
      plant species diversity, richness, and abundance collected by conventional woody
      plant inventory methods. The study was conducted in 21 SAF patches in Northern
      Parana State, Brazil. The phytosociological inventory was conducted along a
      single transect and required 2 days to complete (excluding time spent for
      herbarium identification), whereas REA was conducted along three to four
      transects per working day. REA results correlated positively with woody plant
      diversity, proving REA to be an efficient method for defining the conservation
      status of SAF fragments, but accuracy of evaluations of threats to biological
      integrity are relatively low. Both the selection of appropriate variables and the
      skill level of field staff are critical and can strongly influence REA results.

PMID- 22996824
TI  - Assessment and monitoring of long-term forest cover changes in Odisha, India
      using remote sensing and GIS.
AB  - Deforestation and fragmentation are important concerns in managing and conserving
      tropical forests and have global significance. In the Indian context, in the last
      one century, the forests have undergone significant changes due to several
      policies undertaken by government as well as increased population pressure. The
      present study has brought out spatiotemporal changes in forest cover and
      variation in forest type in the state of Odisha (Orissa), India, during the last
      75 years period. The mapping for the period of 1924-1935, 1975, 1985, 1995 and
      2010 indicates that the forest cover accounts for 81,785.6 km(2) (52.5 %),
      56,661.1 km(2) (36.4 %), 51,642.3 km(2) (33.2 %), 49,773 km(2) (32 %) and
      48,669.4 km(2) (31.3 %) of the study area, respectively. The study found the net
      forest cover decline as 40.5 % of the total forest and mean annual rate of
      deforestation as 0.69 % year(-1) during 1935 to 2010. There is a decline in
      annual rate of deforestation during 1995 to 2010 which was estimated as 0.15 %.
      Forest type-wise quantitative loss of forest cover reveals large scale
      deforestation of dry deciduous forests. The landscape analysis shows that the
      number of forest patches (per 1,000) are 2.463 in 1935, 10.390 in 1975, 11.899 in
      1985, 12.193 in 1995 and 15.102 in 2010, which indicates high anthropogenic
      pressure on the forests. The mean patch size (km(2)) of forest decreased from
      33.2 in 1935 to 5.5 in 1975 and reached to 3.2 by 2010. The study demonstrated
      that monitoring of long term forest changes, quantitative loss of forest types
      and landscape metrics provides critical inputs for management of forest
      resources.

PMID- 22996825
TI  - Synthesis of 11-cis-retinoids by hydrosilylation-protodesilylation of an 11,12
      didehydro precursor: easy access to 11- and 12-mono- and 11,12
      dideuteroretinoids.
AB  - An expeditious, highly efficient approach to 11-cis-retinoids was achieved by
      semihydrogenation of a readily available 11-yne precursor through a
      hydrosilylation-protodesilylation protocol. The complete chemo-, regio-, and syn
      stereoselectivity of the method also allowed direct access to 11- and 12
      monodeutero-, and 11,12-dideutero-11-cis-retinoids. The analogous trans series
      was not accessible by this route, and was synthesized by means of Hiyama
      coupling.

PMID- 22996826
TI  - Neonatal post-hemorrhagic hydrocephalus resulting in foraminal septae
      radiological technique and surgical implications.
AB  - BACKGROUND: Intraventricular haemorrhage is the most common cause of
      hydrocephalus in a pre-term baby and may require surgical intervention depending
      on severity. CLINICAL CASE: This case illustrates foraminal septae as a subtle
      cause of progressive quadriventricular hydrocephalus in a child born pre-term
      with a history of grade III intraventricular haemorrhage. The septae within the
      fourth ventricular exits were clearly demonstrated with 3D-FIESTA (fast imaging
      employing steady-state acquisition) MRI acquisitions and assisted in
      differentiation from communicating hydrocephalus. This finding guided the
      decision to a successful endoscopic third ventriculostomy. CONCLUSION: 3D-FIESTA
      sequence is recommended for investigating children with hydrocephalus secondary
      to intraventricular haemorrhage due to its diagnostic potential and implications
      on surgical technique.

PMID- 22996827
TI  - Tracing synaptic connectivity onto embryonic stem cell-derived neurons.
AB  - Transsynaptic circuit tracing using genetically modified rabies virus (RV) is an
      emerging technology for identifying synaptic connections between neurons.
      Complementing this methodology, it is now possible to assay the basic molecular
      and cellular properties of neuronal lineages derived from embryonic stem cells
      (ESCs) in vitro, and these properties are under intense investigation toward
      devising cell replacement therapies. Here, we report the generation of a novel
      mouse ESC (mESC) line that harbors the genetic elements to allow RV-mediated
      transsynaptic circuit tracing in ESC-derived neurons and their synaptic networks.
      To facilitate transsynaptic tracing, we have engineered a new reporter allele by
      introducing cDNA encoding tdTomato, the Rabies-G glycoprotein, and the avian TVA
      receptor into the ROSA26 locus by gene targeting. We demonstrate high-efficiency
      differentiation of these novel mESCs into functional neurons, show their capacity
      to synaptically connect with primary neuronal cultures as evidenced by
      immunohistochemistry and electrophysiological recordings, and show their ability
      to act as source cells for presynaptic tracing of neuronal networks in vitro and
      in vivo. Together, our data highlight the potential for using genetically
      engineered stem cells to investigate fundamental mechanisms of synapse and
      circuit formation with unambiguous identification of presynaptic inputs onto
      neuronal populations of interest.

PMID- 22996828
TI  - Requirement of insertion sequence IS1 for thermal adaptation of Pro-Tk-subtilisin
      from hyperthermophilic archaeon.
AB  - Tk-subtilisin from the hyperthermophilic archaeon Thermococcus kodakarensis
      matures from Pro-Tk-subtilisin (Pro-TKS) upon autoprocessing and degradation of
      propeptide. Pro-TKS contains the insertion sequence (IS1) at the N-terminus of
      the mature domain as compared to bacterial pro-subtilisins. To analyze the role
      of IS1, the Pro-TKS derivative without IS1 (?IS1-Pro-TKS) and its active-site
      mutants (?IS1-Pro-S324A and ?IS1-Pro-S324C) were constructed and characterized.
      ?IS1-Pro-S324A and ?IS1-Pro-TKS represent an unautoprocessed and autoprocessed
      form of ?IS1-Pro-TKS, respectively. The CD and ANS fluorescence spectra of these
      proteins indicate that folding of ?IS1-Pro-TKS is not completed by binding of
      Ca(2+) ions but is completed by the subsequent autoprocessing reaction. Thermal
      denaturation of these proteins analyzed by DSC and CD spectroscopy indicates that
      unautoprocessed ?IS1-Pro-TKS is less stable than autoprocessed ?IS1-Pro-TKS by
      26.3  degrees C in T (m). The stability of autoprocessed ?IS1-Pro-TKS is
      comparable to that of Pro-TKS, which is slightly lower than that of
      unautoprocessed Pro-TKS. These results suggest that ?IS1-Pro-TKS is fully folded
      and greatly stabilized by autoprocessing. ?IS1-Pro-TKS more slowly matured to
      ?IS1-Tk-subtilisin than Pro-TKS did, due to a decrease in the autoprocessing
      rate. We propose that IS1 is required not only for hyperstabilization of Pro-TKS
      but also for its rapid maturation.

PMID- 22996829
TI  - Distinct features of protein folding by the GroEL system from a psychrophilic
      bacterium, Colwellia psychrerythraea 34H.
AB  - We investigated the protein folding mechanism of the GroEL system of a
      psychrophilic bacterium, Colwellia psychrerythraea 34H. The amount of mRNA of the
      groESL operon of C. psychrerythraea was increased about 6-fold after a
      temperature upshift from 8 to 18  degrees C for 30 min, suggesting that this
      temperature causes heat stress in this bacterium. A sigma(32)-type promoter was
      found upstream of the groESL, suggesting that the C. psychrerythraea groESL is
      regulated by the sigma(32) system, like the groESL in E. coli. The maximum ATPase
      and CTPase activities of CpGroEL were observed at 45 and 35  degrees C,
      respectively, which are much higher than the growth temperatures of C.
      psychrerythraea. We found that the refolding activity of the CpGroEL system in
      the presence of ATP is lower than that in the presence of CTP. This suggests that
      ATP is not the optimum energy source of the CpGroEL system. Analyses for the
      interaction of CpGroEL-CpGroES revealed that CTP could weaken this interaction,
      resulting in effective refolding function of the CpGroEL system. From these
      findings, we consider that the CpGroEL system possesses an energy-saving
      mechanism for avoiding excess consumption of ATP to ensure growth in a low
      temperature environment.

PMID- 22996830
TI  - Microvascularity in transition zone prostate tumors resembles normal prostatic
      tissue.
AB  - BACKGROUND: The objective of this study was comparison of characteristics of the
      microvasculature in transition zone tumor (TZT) and benign nodular hyperplasia
      (BPH) with normal prostatic transition zone (NTZ), applying accurate and
      objective quantification based on digital image analysis. Results of this study
      may increase understanding of prostate dynamic contrast enhanced (DCE) MRI
      analysis. METHODS: Radical prostatectomy specimens of 28 patients containing TZT
      ranging from pT2-pT4 were used. In 11 patients a concomitant peripheral zone
      tumor (PZT) was present. Microvessels were visualized by CD31
      immunohistochemistry. Specimens were scanned using a computer-controlled
      microscope with automatic recognition of microvessels. Pseudocolor maps were
      produced displaying microvessel density, perimeter, and area of an entire
      prostate transection. Mean, 75th percentile (p75) and coefficient of variation
      (CV) were calculated automatically in manually indicated areas of the tumor and
      corresponding contralateral normal tissue, and BPH. RESULTS: Large variability
      was seen in TZT microvascular parameters, indicating presence of patients having
      both hypo and hypervascularized tumors compared to NTZ. In contrast, areas of BPH
      showed a more consistent increase in vascular parameters, with decreased CV.
      Analysis of PZT confirmed results of our previous study, with mean and p75 of all
      vascular parameters being significantly increased and a decrease in CV. No
      correlation was found for clinicopathological parameters and microvascular
      parameters. CONCLUSION: Microvasculature of transition zone tumor showed
      increased heterogeneity compared to BPH and peripheral zone tumors, possibly
      explaining the difficulty of TZT detection on DCE-MRI.

PMID- 22996831
TI  - Accuracy of low-dose rubidium-82 myocardial perfusion imaging for detection of
      coronary artery disease using 3D PET and normal database interpretation.
AB  - BACKGROUND: Our aim was to develop a normal database to be used for
      quantification of myocardial perfusion and diagnosis of "obstructive coronary
      artery disease" (CAD) using low-dose rubidium-82 three-dimensional (3D) positron
      emission tomography (PET)-CT. METHODS: From a record of 1,501 patients, 77 were
      identified as having low-likelihood (LLK) of CAD. Forty LLK patients were used to
      construct a normal database using 4DM-PET, the remainder used for validation of
      normalcy. A group of 70 patients with CAD who had invasive coronary angiography
      and PET-CT were used to evaluate the accuracy of the database for detecting CAD
      using the sum-stress-score. The effect of clinical exclusion criteria and the
      inclusion of LLK patients were evaluated. RESULTS: The normal database for CAD
      detection had a normalcy rate of 95%. Sensitivity was 100% for detecting patients
      with either 50% or 70% stenosis. Optimal specificity was 87% for either 50% or
      70% stenosis. For localizing disease at 50% stenosis in the left anterior
      descending, left circumflex, and right coronary artery, sensitivity ranged from
      59% to 68%, while specificity was maintained at 87-89%. Similarly, at 70%
      stenosis, sensitivity ranged from 64% to 79%, and specificity from 87% to 91%.
      CONCLUSIONS: A normal database containing the relative perfusion scores of
      patients with LLK of CAD can be used to accurately diagnose obstructive coronary
      disease using low-dose Rb-82 with 3D PET-CT imaging.

PMID- 22996832
TI  - The evolving practice of nuclear cardiology: results from the 2011 ASNC member
      survey.
AB  - BACKGROUND: Today's imaging laboratories face challenges including reimbursement,
      prior authorization, and accreditation standards. The impact on the practice of
      nuclear cardiology in the United States is unknown. We conducted a survey of ASNC
      members to provide a snapshot of nuclear cardiology imaging laboratories in 2011.
      METHODS AND RESULTS: The survey identified practice patterns including personnel,
      volumes, protocols used, and laboratory characteristics. We employed random
      sampling methodology stratified geographically. The response rate was 19.5%
      (73/374 laboratories). A non-random survey conducted in 2001 of 25 laboratories
      served as a comparator. A total of 73 laboratories, representing 202 physicians
      and 177 technologists responded. The reported median procedural volume was 1,225
      studies annually; 88.9% of laboratories were accredited. Compared with 2001, dual
      isotope imaging protocol use dropped from 72% to 15.6%. Five markers of quality
      were surveyed. Half of laboratories use the American College of Cardiology's
      Appropriate Use Criteria, 61% used segmental scoring, and 32% provided guidance
      on post-test therapeutic management. 89% perform catheterization correlations
      while only 33% implemented radiation dose tracking. CONCLUSIONS: This survey of
      ASNC members provides critical information on nuclear cardiology practice to
      better target and service our members' needs. These data can prove invaluable to
      target educational needs and inform healthcare policy of contemporary nuclear
      cardiology practice.

PMID- 22996833
TI  - Risk assessment in the era of high-speed myocardial perfusion imaging.

PMID- 22996834
TI  - Deriving respiration from photoplethysmographic pulse width.
AB  - A method for deriving respiration from the pulse photoplethysmographic (PPG)
      signal is presented. This method is based on the pulse width variability (PWV),
      and it exploits the respiratory information present in the pulse wave velocity
      and dispersion. It allows to estimate respiration signal from only a pulse
      oximeter which is a cheap and comfortable sensor. Evaluation is performed over a
      database containing electrocardiogram (ECG), blood pressure (BP), PPG, and
      respiratory signals simultaneously recorded in 17 subjects during a tilt table
      test. Respiratory rate estimation error is computed obtaining of 1.27 +/- 7.81%
      (0.14 +/- 14.78 mHz). For comparison purposes, we have also obtained a
      respiratory rate estimation from other known methods which involve ECG, BP, or
      also PPG signals. In addition, we have also combined respiratory information
      derived from different methods which involve only PPG signal, obtaining a
      respiratory rate error of -0.17 +/- 6.67% (-2.16 +/- 12.69 mHz). The presented
      methods, PWV and combination of PPG derived respiration methods, avoid the need
      of ECG to derive respiration without degradation of the obtained estimates, so it
      is possible to have reliable respiration rate estimates from just the PPG signal.

PMID- 22996835
TI  - Shoulder sonography after intraarticular fluid injection for evaluation of
      anterior labral tears: comparison with conventional sonography.
AB  - PURPOSE: To compare shoulder sonography (US) after intraarticular fluid injection
      ("arthrosonography") with conventional shoulder US for diagnosing anterior labral
      tears. METHODS: Thirty consecutive patients who were to undergo shoulder MR
      arthrography were enrolled after written informed consent was obtained. A
      radiologist performed conventional US, using a 2- to 5-MHz convex transducer on
      the subject whose arm was externally rotated, then abducted perpendicular to the
      trunk, and rotated internally and externally. After intraarticular injection of
      diluted gadolinium contrast for MR arthrography, arthrosonography was performed
      in the same manner as in the conventional method. Two other radiologists compared
      the two US methods in the diagnosis of anterior labral tears using a five-point
      scale. Receiver operating characteristic (ROC) curves and weighted kappa values
      were calculated. RESULTS: Fourteen patients proven to have anterior labral tears
      by arthroscopy constituted the disease group, and 16 patients, including the 4
      patients who were negative on arthroscopy, constituted the normal group. The
      areas under the ROC curve of arthrosonography (mean, 0.977) were larger than
      those of conventional US (mean, 0.858). The kappa values for assessing the
      interobserver agreement of the two modalities were 0.40 and 0.82, respectively.
      CONCLUSIONS: Arthrosonography of the shoulder is more accurate and reliable than
      conventional US for diagnosing anterior labral tear.

PMID- 22996836
TI  - Lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) causes
      hyperactivity in male rat pups by aberrant increase in dopamine and its receptor.
AB  - Polychlorinated biphenyls (PCBs) are recognized as persistent environmental
      pollutants that may cause adverse health problems. Despite extensive
      investigations of PCB in neural function, little is known about behavioral traits
      by PCB exposure and its neurochemical mechanism. Here, we report the behavioral
      study of a rat pup that was exposed to hydroxylated-PCB 106 (OH-PCB 106; 4
      hydroxy-2',3,3',4',5'-pentachlorobiphenyl) through maternal milk. The different
      groups of mothers received via gavage corn oil vehicle, 0.5, 5, or 50 mg/kg body
      weight of OH-PCB 106 every second day from day 3 to 13 after delivery. The
      exposure did not affect the body weight of the dams or the physical development
      of the newborn pups in both sexes. Male rats exposed to OH-PCB 106 showed
      hyperactivity that was characterized by increased locomotor activity in novel
      environment and circadian period. Interestingly, OH-PCB 106-exposed rat pups
      displayed abnormally high levels of dopamine and D2 dopamine receptor (D2DR), but
      not D1DR and D5DR, in the striatum, an important center for the coordination of
      behavior. These findings indicate that OH-PCB 106 has a significant neurotoxic
      effect on rat behavior, which may be associated with increased D2DR mediated
      signals.

PMID- 22996837
TI  - Relative impact of flavonoid composition, dose and structure on vascular
      function: a systematic review of randomised controlled trials of flavonoid-rich
      food products.
AB  - SCOPE: Previous systematic reviews suggest beneficial effects of flavonoids on
      biomarkers of cardiovascular disease (CVD) risk, but have overlooked the impact
      of dose response or food complexity. The aim of the present study was to examine
      the relative impact of composition, flavonoid structure and dose. METHODS AND
      RESULTS: MEDLINE, EMBASE and Cochrane were searched for randomised controlled
      trials (RCTs) of flavonoids or flavonoid-rich foods/extracts. Flavonoid
      composition was established using United States Department of Agriculture (USDA)
      and Phenol-Explorer databases. Effects of six flavonoid subgroups on endothelial
      function (flow-mediated dilation; FMD), and systolic and diastolic blood
      pressures were assessed by random effects meta-analyses and regression analyses.
      Meta-analyses of combined flavonoid subclasses showed significant improvements in
      FMD (chronic, 0.73% (0.17, 1.30) 14 RCTs; acute, 2.33% (1.58, 3.08) 18 RCTs) and
      blood pressures (systolic, -1.46 mmHg (-2.38, -0.53) 63 RCTs; diastolic, -1.25
      mmHg (-1.82, -0.67) 63 RCTs). Similar benefits were observed for the flavan-3-ol,
      catechol flavonoids (catechins, quercetin, cyanidin etc.), procyanidins,
      epicatechin and catechin subgroups. Dose-response relationships were non-linear
      for FMD (R(2)  <= 0.30), with greater associations observed when applying
      polynomial regression analyses (R(2)  <= 0.72); there was no indication of a dose
      response for blood pressure. CONCLUSION: The present analysis suggests that
      flavonoid bioactivity does not follow a classical linear dose-response
      association and this may have important biological implications.

PMID- 22996838
TI  - A dicationic ruthenium alkylidene complex for continuous biphasic metathesis
      using monolith-supported ionic liquids.
AB  - A dicationic ruthenium-alkylidene complex [Ru(dmf)(3)(IMesH(2))(=CH-2-(2-PrO)
      C(6)H(4))][(BF(4))(2)] (1; IMesH(2) =1,3-dimesitylimidazolin-2-ylidene) has been
      prepared and used in continuous metathesis reactions by exploiting supported
      ionic-liquid phase (SILP) technology. For these purposes, ring-opening metathesis
      polymerization (ROMP)-derived monoliths were prepared from norborn-2-ene,
      tris(norborn-5-ene-2-ylmethyloxy)methylsilane, and [RuCl(2)(PCy(3))(2)(CHPh)]
      (Cy=cyclohexyl) in the presence of 2-propanol and toluene and surface grafted
      with norborn-5-en-2-ylmethyl-N,N,N-trimethylammonium tetrafluoroborate ([NBE
      CH(2)-NMe(3)][BF(4)]). Subsequent immobilization of the ionic liquid (IL), 1
      butyl-2,3-dimethylimidazolium tetrafluoroborate ([BDMIM][BF(4)]), containing
      ionic catalyst 1 created the SILP catalyst. The use of a second liquid transport
      phase, which contained the substrate and was immiscible with the IL, allowed
      continuous metathesis reactions to be realized. High turnover numbers (TONs) of
      up to 3700 obtained in organic solvents for the ring-closing metathesis (RCM) of,
      for example, N,N-diallyltrifluoroacetamide, diethyl diallylmalonate, diethyl
      di(methallyl)malonate, tert-butyl-N,N-diallylcarbamate, N,N-diallylacetamide,
      diphenyldiallylsilane, and 1,7-octadiene, as well as in the self-metathesis of
      methyl oleate, could be further increased by using biphasic conditions with
      [BDMIM][BF(4)]/heptane. Under continuous SILP conditions, TONs up to 900 were
      observed. Due to the ionic character of the initiator, catalyst leaching into the
      transport phase was very low (<0.1 %). Finally, the IL can, together with
      decomposed catalyst, be removed from the monolithic support by flushing with
      methanol. Upon reloading with [BDMIM][BF(4)]/1, the recycled support material
      again qualified for utilization in continuous metathesis reactions.

PMID- 22996842
TI  - Young Spanish researcher wins Opitz award: winning paper describes new progeria
      syndrome.

PMID- 22996839
TI  - Targeted cargo delivery in senescent cells using capped mesoporous silica
      nanoparticles.
AB  - Learning to let go with age: Intracellular controlled release of molecules within
      senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped
      with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta
      spheres; see scheme). The GOS is a substrate of the senescent biomarker,
      senescence-associated beta-galactosidase (SA-beta-gal), and releases the cargo
      upon entry into SA-beta-gal expressing cells.

PMID- 22996843
TI  - Healthcare reform law benefits children with genetic diseases: despite law's
      benefits, many questions about coverage remain.

PMID- 22996845
TI  - Theoretical and experimental investigations on migration behavior of weak
      monoprotic acids in continuous two-dimensional ion exchange/reversed phase CEC.
AB  - A continuous 2D ion exchange/RP CEC system was constructed in this report and
      retention characteristics of weak monoprotic acids in the column were
      investigated theoretically. The transport equations were deduced for predicting
      migration behavior of weak monoportic acids based on mixing model combining ion
      exchange, RP, and electrophoretic separation mechanism. The influences of
      separation voltage, length of capillary, pH value, and ionic strength of buffer
      and concentration of organic modifier in mobile phase on the separation were well
      described by the equations. It was verified that the migration rate of solute was
      linearly related to voltage in the case of lower voltage, decreased with the
      increase of the first-dimensional length, and [H+]. The retention time of solute
      increased with enhancing ionic strength and concentration of organic modifier.
      These theoretical results were all demonstrated by the relevant experiments. The
      relevant application was performed for the aqueous extract of Rhizoma gastrodiae,
      showing the obvious potential in method development for the analysis of complex
      samples.

PMID- 22996846
TI  - The effect of occupational exposure to benzo[a]pyrene on neurobehavioral function
      in coke oven workers.
AB  - BACKGROUND: Coke oven workers are regularly exposed to polycyclic aromatic
      hydrocarbons (PAHs). Benzo[a]pyrene (B[a]P), known as an indicator species for
      PAH contamination, is a neurobehavioral toxicant. The purpose of the study was to
      evaluate the relationship between B[a]P exposure, a B[a]P-related urinary
      metabolite and neurobehavioral function among coke oven workers. METHODS: Coke
      oven workers and oxygen factory workers participated in this study. B[a]P
      exposure was monitored by air sampling pump, and urinary 1-hydroxypyrene (1-OHP)
      level was detected with high performance liquid chromatography (HPLC). A
      questionnaire and the neurobehavioral core test battery (NCTB) were administered
      to all subjects. RESULTS: B[a]P-exposed workers were found to have higher urinary
      1-OHP levels and worse NCTB performances on eight items than control workers.
      B[a]P concentrations were higher in the coke oven plant than that in the
      controls' workplace. The performances on simple reaction time, correct pursuit
      aiming, and error pursuit aiming decreased with increasing airborne B[a]P in coke
      oven workers. There were significant correlations between urinary 1-OHP level and
      six items of the NCTB. CONCLUSIONS: Occupational exposure to B[a]P is associated
      with neurobehavioral function impairment in coke oven workers.

PMID- 22996847
TI  - The efficacy of patient education in whiplash associated disorders: a systematic
      review.
AB  - BACKGROUND: Until now, there is no firm evidence for conservative therapy in
      patients with chronic Whiplash Associated Disorders (WAD). While chronic WAD is a
      biopsychosocial problem, education may be an essential part in the treatment and
      the prevention of chronic WAD. However, it is still unclear which type of
      educative intervention has already been used in WAD patients and how effective
      such interventions are. OBJECTIVE: This systematic literature study aimed at
      providing an overview of the literature regarding the currently existing
      educative treatments for patients with whiplash or WAD and their evidence. STUDY
      DESIGN: Systematic review of the literature. METHODS: A systematic literature
      search was conducted in the following databases: Pubmed, Springerlink, and Web of
      Science using different keyword combinations. We included randomized controlled
      clinical trials (RCT) that encompass the effectiveness of education for patients
      with WAD. The included articles were evaluated on their methodological quality.
      RESULTS: Ten RCT's of moderate to good quality remained after screening. Both
      oral and written advice, education integrated in exercise programs and behavioral
      programs appear effective interventions for reducing pain and disability and
      enhancing recovery and mobility in patients with WAD. In acute WAD, a simple oral
      education session will suffice. In subacute or chronic patients broader
      (multidisciplinary) programs including education which tend to modulate pain
      behavior and activate patients seems necessary. LIMITATIONS: Because of limited
      studies and the broad range of different formats and contents of education and
      different outcome measures, further research is needed before solid conclusions
      can be drawn regarding the use and the modalities of these educational
      interventions in clinical practice. CONCLUSION: Based on this systematic
      literature study is seems appropriate for the pain physician to provide education
      as part of a biopsychosocial approach of patients with whiplash. Such education
      should target removing therapy barriers, enhancing therapy compliance and
      preventing and treating chronicity. Still, more studies are required to provide
      firm evidence for the type, duration, format, and efficacy of education in the
      different types of whiplash patients.

PMID- 22996848
TI  - A predictive model for intrathecal opioid dose escalation for chronic non-cancer
      pain.
AB  - BACKGROUND: Tolerance is defined as a phenomenon in which exposure to a drug
      results in a decrease of an effect or the requirement of a higher dose to
      maintain an effect. The fear of a patient developing opioid tolerance contributes
      regularly to the stigmatization and withholding of intrathecal opioid therapy for
      chronic pain of non-cancer origin. OBJECTIVES: The aim of this study was to
      describe the intrathecal opioid dose escalation throughout the years in chronic
      non-cancer pain patients. A secondary objective was the development of an
      intrathecal opioid dose predictive model. STUDY DESIGN: Retrospective assessment
      of medical records. SETTING: Department of Pain Management, Russells Hall
      Hospital, Dudley, United Kingdom. METHODS: Medical records were reviewed and pump
      refill notes screened from the date of implant through November 2010 for 31
      patients undertaking continuous intrathecal opioid therapy. All the patients
      included had undertaken a minimum of 6 years of intrathecal therapy when the data
      were collected. RESULTS: Significant increases in the intrathecal morphine dose
      were verified between follow-up at one year and all subsequent observations, F 
      (2.075, 62.238) = 13.858, 0 < 0.001, but ceased to be significant from year 3
      onwards, indicating stability of the morphine dose, F  (3, 90) = 2.516, P = 0.63.
      A model that accounts for 76% of the variability of morphine doses at year 6
      based on year 2 assessment combined with duration of pain prior to initiation of
      intrathecal therapy was developed: year 6 dose = -0.509 +  (1.296 x [year 2
      dose]) +  (0.061 x [duration of pain]). LIMITATIONS: Retrospective study.
      CONCLUSION: The opioid dose escalation observed throughout the years was modest
      and not significant following year 3 of therapy. The model developed has the
      potential to assist the physician in the identification of a need for alternative
      treatment strategies. Furthermore, since many of the pump replacements are
      performed prior to year 6, it can also assist in the informed decision of the
      benefits and risks of the maintenance of this therapy.

PMID- 22996849
TI  - Results of 2-year follow-up of a randomized, double-blind, controlled trial of
      fluoroscopic caudal epidural injections in central spinal stenosis.
AB  - BACKGROUND: Lumbar spinal stenosis is one of the most common causes of low back
      pain among older adults and can cause significant disability. Despite its
      prevalence, there is a paucity of literature concerning the treatment of spinal
      stenosis symptoms. Multiple interventions, including surgery and interventional
      techniques such as epidural injections and adhesiolysis, are commonly utilized in
      managing pain related to central spinal stenosis. However, there is a paucity of
      literature from randomized, controlled trials about the effectiveness of epidural
      injections for lumbar central spinal stenosis. OBJECTIVE: This study sought to
      assess the effectiveness of caudal epidural injections with or without steroids
      in providing effective and long-lasting pain relief for the management of chronic
      low back pain related to lumbar central stenosis. STUDY DESIGN: A randomized,
      double-blind, active-controlled trial. METHODS: One hundred patients were
      randomly assigned to one of 2 groups, with Group I patients receiving caudal
      epidural injections of local anesthetic  (lidocaine 0.5%), whereas Group II
      patients received caudal epidural injections with 0.5% lidocaine 9 mL mixed with
      1 mL of steroid, 6 mg  (non-particulate betamethasone). OUTCOMES ASSESSMENT:
      Multiple outcome measures, including the Numeric Rating Scale  (NRS), the
      Oswestry Disability Index 2.0  (ODI), employment status, and opioid intake were
      utilized. Assessments were carried out at 3, 6, 12, 18, and 24 months
      posttreatment.  The primary outcome was defined as pain relief and improvement in
      disability scores of 50% or more. Successful treatment was considered as at least
      3 weeks of relief following the first 2 injections, categorizing these patients
      into a successful group, and others into a failed group. RESULTS: Significant
      pain relief and functional status improvement were seen in 51% in Group I and 57%
      in Group II at the end of 2 years in the successful group when the participants
      were separated into successful and failed groups. However, overall, significant
      pain relief and functional status improvement  (>= 50%) was demonstrated in 38%
      in Group I and 44% in Group II at the end of 2 years. The overall number of
      procedures for 2 years were 4 in both groups, with 5 procedures on average in the
      successful groups, and approximately 60 weeks of relief in Group I and 54 weeks
      of relief in Group II at 2 years in the successful group. CONCLUSION: Caudal
      epidural injections of local anesthetic with or without steroids provide relief
      in a modest proportion of patients undergoing the treatment and may be considered
      as an effective treatment for a select group of patients who have chronic
      function-limiting low back and lower extremity pain secondary to central spinal
      stenosis.

PMID- 22996850
TI  - Central adaptation of pain perception in response to rehabilitation of
      musculoskeletal pain: randomized controlled trial.
AB  - BACKGROUND: Understanding the mechanisms of long-standing musculoskeletal pain
      and adaptations in response to physical rehabilitation is important for
      developing optimal treatment strategies. The influence of central adaptations of
      pain perception in response to rehabilitation of musculoskeletal pain remains
      unclear. OBJECTIVE: To investigate the effect of neck/shoulder resistance
      training on pressure pain threshold (PPT) of the painful neck/shoulder muscles
      (upper trapezius) and a non-painful reference muscle of the leg (tibialis
      anterior) in adults with neck/shoulder pain. STUDY DESIGN: Examiner-blinded,
      parallel-group randomized controlled trial with allocation concealment. TRIAL
      REGISTRATION: ISRCTN60264809 SETTING: Office workplaces in the capital of
      Denmark. METHODS: The study contained 198 adults with frequent neck/shoulder pain
      (174 women and 24 men, mean: age 43 years, duration of pain 186 days during the
      previous year, computer use 93% of work time) were randomly allocated to 10 weeks
      of specific resistance training for the neck/shoulder muscles for 2 or 12 minutes
      per day 5 times a week, or weekly information on general health (control group).
      Primary outcomes were changes in PPT of the painful neck/shoulder muscles (upper
      trapezius) and a distant non-painful reference muscle (tibialis anterior) at 10
      weeks. RESULTS: PPT of both the trained painful trapezius and the non-trained
      reference muscle of the leg increased more in the training groups compared with
      the control group (P < 0.05), providing evidence of central adaptations. The
      change in PPT of the reference muscle was of similar magnitude to that of the
      painful muscle. Compared with the control group, the change in PPT of the
      trapezius and tibialis anterior was 31 (95% CI 3 to 60) kPa and 36 (8 to 65) kPa
      in the 2 min group, respectively, and 29 (1 to 58) kPa and 36 (7 to 64) kPa in
      the 12 min group. LIMITATIONS: Blinding of participants is not possible in
      behavioural interventions. CONCLUSION: Central adaptations of pain perception
      occur in response to rehabilitation of musculoskeletal pain. Thus, treating pain
      in one region of the body reduces sensitivity to pressure in other regions of the
      body. Clinicians and researchers may use this knowledge to better understand
      adaptations of pain perception in patients with musculoskeletal pain.

PMID- 22996851
TI  - Ziconotide adverse events in patients with cancer pain: a multicenter
      observational study of a slow titration, multidrug protocol.
AB  - BACKGROUND: Ziconotide is a new analgesic agent administered intrathecally. It is
      challenging to use and can induce several and sometimes serious adverse events. A
      low initial dosage followed by slow titration may reduce serious adverse events.
      OBJECTIVE: To determine whether a low starting dosage of ziconotide, followed by
      slow titration, decreases the incidence of major adverse events associated with
      ziconotide when used for intractable cancer pain. STUDY DESIGN: Observational
      cohort study. SETTING: Three French cancer centers. METHODS: Patients with
      incurable cancer causing chronic pain rated above 6/10 on a numerical scale while
      receiving high-dose opioid therapy  (more than 200 mg/d of oral morphine
      equivalent) and/or exhibiting severe opioid-related adverse events received
      intrathecal infusions of ziconotide combined with morphine, ropivacaine, and
      clonidine. RESULTS: Seventy-seven patients were included. Adverse events were
      recorded in 57% of them; moderate adverse events occurred in 51%. Adverse events
      required treatment discontinuation in 7  (9%) including 5  (6%) for whom a causal
      role for ziconotide was highly likely; among them 4  (5%) were serious. All
      patients experienced a significant and lasting decrease in pain intensity  (by
      48%) in response to intrathecal analgesic therapy that included ziconotide.
      LIMITATIONS: Limitations include the nonrandomized, observational nature of the
      study. Determining the relative contributions of each drug to adverse events was
      difficult, and some of the adverse events manifested as clinical symptoms of a
      subjective nature. CONCLUSIONS: The rates of minor and moderate adverse events
      were consistent with previous reports. However, the rate of serious adverse
      events was substantially lower. Our study confirms the efficacy of intrathecal
      analgesia with ziconotide for relieving refractory cancer pain. These results
      indicate that multimodal intrathecal analgesia in patients with cancer pain
      should include ziconotide from the outset in order to provide time for subsequent
      slow titration.

PMID- 22996852
TI  - Altered perception of distorted visual feedback occurs soon after whiplash
      injury: an experimental study of central nervous system processing.
AB  - BACKGROUND: Sensory and motor system dysfunctions have been documented in a
      proportion of patients with acute whiplash associated disorders (WAD).
      Sensorimotor incongruence may occur and hence, may explain pain and other
      sensations in the acute stage after the trauma. OBJECTIVES: The present study
      aimed at (1) evaluating whether a visually mediated incongruence between sensory
      feedback and motor output increases symptoms and triggers additional sensations
      in patients with acute WAD, (2) investigating whether the pattern of sensations
      in response to sensorimotor incongruence differs among patients suffering from
      acute and chronic WAD, and healthy controls. STUDY DESIGN: Experimental study.
      SETTING: Patients with acute WAD were recruited within one month after whiplash
      injury via the emergency department of a local Red Cross medical care unit, the
      Antwerp University Hospital, and through primary care practices. Patients with
      chronic WAD were recruited through an advertisement on the World Wide Web and
      from the medical database of a local Red Cross medical care unit. Healthy
      controls were recruited from among the university college staff, family members,
      and acquaintances of the researchers. METHODS: Thirty patients with acute WAD, 35
      patients with chronic WAD, and 31 healthy persons were subjected to a
      coordination test. They performed congruent and incongruent arm movements while
      viewing a whiteboard or mirror. RESULTS. Twenty-eight patients with acute WAD
      reported sensations such as pain, tightness, feeling of peculiarity, and
      tiredness at some stage of the test protocol. No significant differences in
      frequencies and intensities of sensations were found between the various test
      stages (P > .05). Significantly more sensations were reported during the
      incongruent mirror stage compared to the incongruent control stage (P < .05). The
      pattern in intensity of sensations across the congruent and incongruent stages
      was significantly different between the WAD groups and the control group.
      LIMITATIONS: The course and prognostic value of susceptibility to sensorimotor
      incongruence after an acute whiplash trauma are not yet clear from these results.
      A prospective longitudinal study with an expanded study population is needed to
      investigate if those with a lowered threshold to visually mediated sensorimotor
      incongruence in the acute stage are at risk to develop persistent pain and
      disability. CONCLUSION: Patients with acute WAD present an exacerbation of
      symptoms and additional sensations in response to visually mediated changes
      during action. These results indicate an altered perception of distorted visual
      feedback and suggest altered central sensorimotor nervous system processing in
      patients with acute WAD.

PMID- 22996853
TI  - The efficacy of transforaminal epidural steroid injection by the conventional
      technique in far-lateral herniation of lumbar disc.
AB  - BACKGROUND: Owing to the anatomical difference between the far lateral herniation
      of the lumbar disc (FHLD) and the intraspinal herniation of lumbar disc (iHLD),
      the outcome of transforaminal epidural steroid injections (TFESI) in patients
      with FHLD seems to be different from that in patients with iHLD. However, few
      studies have evaluated the efficacy of TFESI in FHLD. OBJECTIVE: To evaluate and
      compare the efficacy of TFESI in FHLD and iHLD patients. STUDY DESIGN: A
      retrospective design. METHODS: There were 15 and 70 patients in the FHLD and iHLD
      groups, respectively. Patients received a fluoroscopically guided TFESI. Failure
      rates of TFESI were recorded, and questionnaires, including a visual analog scale
      (VAS) for leg pain and Oswestry disability index (ODI) were administered before
      the initial injection, at 2 weeks, 6 weeks, and 12 weeks after the injections.
      RESULTS: There was no failure for TFESI in the iHLD group, while 9 patients had
      to undergo alternative blocks in the FHLD group due to lancinating leg pain when
      the needle was advanced for TFESI. In the iHLD group, there was a statistically
      significant improvement in the VAS and ODI score 12 weeks after injection.
      Considering only successful cases of the FHLD group, significant improvement in
      the VAS and ODI score was also demonstrated in the FHLD group 12 weeks after
      injection. Moreover, there was no statistically significant difference of the VAS
      and ODI between the both groups. LIMITATIONS: A relatively small numbers of cases
      were included in the FHLD group. CONCLUSION: The current study suggests that an
      alternative needle placement technique for TFESI appears to be necessary for FHLD
      patients.

PMID- 22996854
TI  - Multivariate prognostic modeling of persistent pain following lumbar discectomy.
AB  - BACKGROUND: Persistent postsurgical pain (PPSP) affects between 10% and 50% of
      surgical patients, the development of which is a complex and poorly understood
      process. To date, most studies on PPSP have focused on specific surgical
      procedures where individuals do not suffer from chronic pain before the surgical
      intervention. Individuals who have a chronic nerve injury are likely to have
      established peripheral and central sensitization which may increase the risk of
      developing PPSP. Concurrent analyses of the possible factors contributing to the
      development of PPSP following lumbar discectomy have not been examined.
      OBJECTIVE: The aim of this study is to identify risk and protective factors that
      predict the course of recovery following lumbar discectomy and to develop an
      easily applicable preoperative multivariate prognostic model for the occurrence
      of PPSP in this patient cohort. STUDY DESIGN: A prospective study of elective
      lumbar discectomy with a 3 month follow-up. SETTING: University setting in
      Ireland. METHODS: All ASA I-II patients, (n = 53, 18-65 years old), undergoing
      elective lumbar discectomy at a single institute were included and followed for a
      3 month period postsurgery. Preoperative potential predictors were collected:
      age, gender, pain intensity (McGill score, visual analog scale [VAS], Present
      Pain Intensity), degree of dysfunction (Roland-Morris Function score),
      psychological status (pain catastrophizing, anxiety, and depression scores),
      health-related quality of life (SF-36), quantitative sensory testing (QST),
      inflammatory biomarkers, and a genetic pain profile. The proposed primary outcome
      was significant pain reduction (VAS > 70%) 3 months following surgery compared to
      the preoperative pain intensity. RESULTS: A final prediction model was obtained
      using a multivariate logistic regression in combination with bootstrapping
      techniques for internal validation. Twenty (37.7%) patients developed PPSP.
      Independent predictor factors included age (odds ratio [OR] = 1.0 per year),
      present pain intensity (OR = 0.6), and degree of dysfunction (OR = 1.2). The
      concordance index C (.658) supports a good monotonic association (where perfect
      prediction is 1) and the Akaike's information criteria indicated a good fit of
      the model. Inclusion of additional measured parameters (QST, biomarker, or
      genotyping) did not improve the model. LIMITATIONS: Before this internally
      validated model can be integrated into clinical practice, and used for patient
      counselling and quality assurance purposes, external validation studies are
      necessary. CONCLUSIONS: We demonstrated that the occurrence of PPSP can be
      predicted using a small set of variables easily obtained at the preoperative
      visit. This a prediction rule that could further optimize perioperative pain
      treatment and reduce attendant complications by allowing the preoperative
      classification of surgical patients according to their risk of developing PPSP.

PMID- 22996855
TI  - Acute cauda equina syndrome secondary to a lumbar synovial cyst.
AB  - Cauda equina syndrome is a well described state of neurologic compromise due to
      lumbosacral root compression. In most cases, it is due to a herniated disc,
      tumor, infection, or hematoma. We report a case of rapid lumbar synovial cyst
      expansion leading to acute cauda equina syndrome and compare it to similar cases
      in the literature.  The patient is a 49-year-old woman with a history of chronic
      low back pain who developed cauda equina syndrome. Serial lumbar magnetic
      resonance imaging studies demonstrated a significant increase in the size of a
      lumbar synovial cyst over a 2 week interval. After an unsuccessful attempt to
      relieve her acute symptoms with computed tomography-guided cyst aspiration, an L4
      5 posterior spinal decompression with excision of the synovial cyst was
      performed.  Postoperatively the patient's perineal numbness, bladder
      incontinence, and associated pain complaints resolved. The only residual symptom
      at one month follow-up was continued numbness in the right lower limb in an L5
      distribution.  This report adds to 6 other well described similar cases found in
      the literature by illustrating several important points. First, a lumbar synovial
      cyst is a rare but possible cause of acute cauda equina syndrome. Second,
      magnetic resonance imaging is the test of choice to diagnose and characterize
      lumbar synovial cysts; serial imaging can detect fluctuations in cyst size.
      Third, percutaneous treatment of lumbar synovial cysts is variable in efficacy
      and proved to be unsuccessful in our patient. Finally, surgical management has
      shown high success rates for symptomatic cysts. Specifically, in the setting of
      acute cauda equina syndrome secondary to a lumbar synovial cyst, urgent surgical
      decompression has led to resolution of neurologic symptoms in most reported
      cases. A lumbar synovial cyst is an uncommon cause of acute cauda equina
      syndrome. Prompt diagnosis and treatment may lead to reduced morbidity associated
      with this condition.

PMID- 22996856
TI  - Assessment of infection control practices for interventional techniques: a best
      evidence synthesis of safe injection practices and use of single-dose medication
      vials.
AB  - BACKGROUND: It is universally accepted that transmission of bloodborne pathogens
      during health care procedures continues to occur because of the use of unsafe and
      improper injection, infusion, and medication administration practices by health
      care professionals in various clinical settings. This resulted in development of
      multiple guidelines based on case reports; however, these case reports are
      confounded by multiple factors without causal relationship to a single factor.
      Even then, single-dose vials used for multiple patients have been singled out and
      became the focus of infection control policies resulting in inordinate expenses
      for practices without improving patient safety. The cost of implementation of
      single dose vial policy in interventional pain management for drugs alone may
      cost $750 million, whereas with single use radional gloves may exceed $1 billion
      per year. STUDY DESIGN: Best evidence synthesis. OBJECTIVE: To critically
      appraise and synthesize the literature on infection control practices for
      interventional techniques, including safe injection and medication vial
      utilization. METHODS: The available literature on infection control practices was
      reviewed. Due to the nature of the studies involved, with the majority being case
      reports, and a few prospective evaluations, quality assessment and clinical
      relevance criteria were not applied. Data sources included relevant literature
      identified through searches of PubMed and EMBASE from 1966 through June 2012,
      literature from the Centers for Disease Control and Prevention (CDC), the U.S.
      Food and Drug Administration (FDA), and manual searches of the bibliographies of
      known primary and review articles. OUTCOME MEASURES: The primary outcome measure
      was correlating infection to a breach of standards in infection control
      practices. The secondary objective was to assess the contribution of single-dose
      vials independently for infection. RESULTS: A total of 60 reports met inclusion
      criteria, with 16 reports related to pain management and other procedures, of
      which 9 reports were attributed to issues related to interventional techniques.
      Based on an estimated 37 infections occurring during 200 million interventional
      techniques from 1997 through 2011, the rate of infection is speculated to be one
      infection for every 5 million interventional pain management procedures. However,
      if 10 times more infections are estimated, the infection rate appears to be one
      infection for every 500,000 interventional pain management procedures. The
      evidence is good for infection related to a breach of infection control
      practices. There is good evidence that contamination of multi-dose or single-dose
      vials can contribute to infection. There was poor evidence that the use of single
      dose vials on multiple patients with appropriate infection control practices
      cause infection in interventional pain management. LIMITATIONS: The limitations
      of this comprehensive best evidence synthesis include the paucity of literature
      and dependence of governmental agencies on their literature without applying
      Institute of Medicine (IOM) criteria for guideline synthesis. CONCLUSION: There
      is good evidence that any breach of sterile practice may result in serious and
      life threatening infections. There is poor evidence for single-dose vials as a
      sole factor causing infections when used in multiple patients in interventional
      pain management settings.

PMID- 22996857
TI  - Proposed physician payment schedule for 2013: guarded prognosis for
      interventional pain management.
AB  - As happens every year, on July 1, 2012, the Centers for Medicare and Medicaid
      Services issued a proposed policy and payment rate for services furnished under
      the Medicare physician fee schedule for 2013. The proposed rule would provide
      certified registered nurse anesthetists to practice independent interventional
      pain management. Other issues, though no less important, include a 27%
      sustainable growth rate formula cut in reimbursement, along with a 2% sequester,
      which could lead to a potential cut of 29%. Since the inception of Medicare
      programs in 1965, several methods have been used to determine the amounts paid to
      physicians for each covered service. The sustainable growth rate was enacted in
      1997 to determine physician payment updates under Medicare Part B. Its intent was
      to reduce Medicare physician payment updates to offset the growth and utilization
      of physician services that exceed gross domestic product growth. This is achieved
      by setting an overall target amount of spending for physicians' services and
      adjusting payment rates annually to reflect differences between actual spending
      and the spending target. Since 2002, the sustainable growth rate has annually
      been used to recommend reductions in Medicare reimbursements. Payments were cut
      in 2002 by 4.8%. Since then, Congress has intervened on multiple occasions to
      prevent additional cuts from being imposed. In this manuscript, we will describe
      important proposed changes to the physician fee schedule. Additionally, the
      impact of multiple changes on interventional pain management will be briefly
      described.

PMID- 22996858
TI  - Obamacare 2012: prognosis unclear for interventional pain management.
AB  - The Patient Protection and Affordable Care Act  (ACA), informally referred to as
      ObamaCare, is a United States federal statute signed into law by President Barack
      Obama on March 23, 2010. ACA has substantially changed the landscape of medical
      practice in the United States and continues to influence all sectors, in
      particular evolving specialties such as interventional pain management. ObamaCare
      has been signed into law amidst major political fallouts, has sustained a Supreme
      Court challenge and emerged bruised, but still very much alive. While proponents
      argue that ObamaCare will provide insurance for almost everyone, with an
      improvement in the quality of and reduction in the cost of health care,,
      opponents criticize it as being a massive bureaucracy laden with penalties and
      taxes, that will ultimately eliminate personal medicine and individual practices.
      Based on the 2 years since the passage of ACA in 2010, the prognosis for
      interventional pain management is unclear. The damage sustained to interventional
      pain management and the majority of medicine practices is irreparable. ObamaCare
      may provide insurance for all, but with cuts in Medicare to fund Obamacare, a
      limited expansion of Medicaid, the inadequate funding of exchanges, declining
      employer health insurance coverage and skyrocketing disability claims, the
      coverage will be practically nonexistent. ObamaCare is composed of numerous
      organizations and bureaucracies charged with controlling the practice of medicine
      through the extension of regulations. Apart from cutting reimbursements and
      reducing access to interventional pain management, administration officials are
      determined to increase the role of midlevel practitioners and reduce the role of
      individual physicians by liberalizing the scope of practice regulations and
      introducing proposals to reduce medical education and training.

PMID- 22996859
TI  - CMS proposal for interventional pain management by nurse anesthetists: evidence
      by proclamation with poor prognosis.
AB  - The Office of Inspector General  (OIG), Department of Health and Human Services 
      (HHS), in a 2009 report, showed that unqualified nonphysicians performed 21% of
      the services. These nonphysicians did not possess the necessary licenses,
      certifications, credentials, or training to perform the services.  Since the time
      the medical profession was founded, advances in treatments and technology, as
      well as educational and training standards, have promoted a desire to go beyond
      the basic scope of practice. Many have sought to broaden the scope of practice
      through legislative efforts and proclamation rather than education and training. 
      In 2001, President Clinton signed into law a rule that permitted states to "opt
      out" of the Centers for Medicare and Medicaid Services'  (CMS) requirement for
      nurse anesthetists to be supervised by any physician. Since then, 17 states have
      adopted this rule. While it was originally intended to help rural areas improve
      access to care, the opt out rule essentially supports any hospital or
      organization that seeks to make a profit or cut costs by allowing nurse
      anesthetists to function as physicians. With the implementation of sweeping
      health care regulations under the Affordable Care Act  (ACA, also popularly known
      as Obamacare), the future of nurses and other professionals has been empowered.
      In fact, it has been proposed that medical training may be reduced by 30%, which
      will in their minds equalize training between nonphysicians and physicians. In
      2010, the Federal Trade Commission  (FTC) issued an opinion exerting their power
      to empower CRNAs with unlimited practice, with threats to opposing parties. In
      the 2013 proposed physician payment rule, CMS is proposing that CRNAs may perform
      interventional pain management services. Interventional pain management is a
      medical discipline with defined interventional techniques to be performed by
      professionals who are well trained and qualified. Without considering the
      consequences of the lack of education and training qualifications for CRNAs to
      offer interventional techniques, the FTC issued their opinion and CMS proposed to
      expand these practice patterns with a policy of improved access and reduced cost.
      However, in reality, the opposite will happen and will increase fraud, reduce
      access due to inappropriate procedures, and increase complications, all as a
      result of privileges by legislation without education. The CMS proposal for
      interventional pain management by nurse anesthetists is a proclamation with a
      poor prognosis.

PMID- 22996860
TI  - Radiocontrast media allergic reactions and interventional pain practice--a
      review.
AB  - BACKGROUND: Millions of interventional pain procedures are performed each year in
      the United States. Interventional pain physicians commonly administer
      radiocontrast media  (RCM) under fluoroscopy for these procedures. However, RCM
      can cause various types of hypersensitivity or allergic type reactions, in an
      acute or delayed fashion. Furthermore, some patients report a prior history of
      hypersensitivity reactions to RCM when presenting to the interventional pain
      clinic. Both scenarios present challenges to the interventional pain physician.
      OBJECTIVE: To describe the various types of hypersensitivity reactions to RCM, as
      well as strategies to prevent and manage these reactions, within the context of
      interventional pain practice. METHOD: A review of the literature from 1975
      through 2011 regarding allergic type reactions to RCM, as well as iodine, and
      shellfish allergy, was undertaken in an effort to review and develop
      recommendations on managing these patients presenting to the interventional pain
      clinic. Keywords used in the literature search were: radiocontrast media,
      contrast allergy, contrast reaction, iodine allergy, shellfish allergy, and
      fluoroscopy. The included articles were concerned with the basic or clinical
      science of contrast allergy, including the physiology, epidemiology, diagnosis,
      and management of such reactions. Meta-analysis, review articles, and case
      reports addressing contrast media reactions were also included. Articles which
      discussed contrast media reactions in a peripheral fashion were excluded.
      RESULTS: In reviewing the literature, it is apparent that the mechanisms and
      pathophysiology of RCM hypersensitivity reactions are still being characterized,
      which should soon lead to improved screenings, as well as prevention and
      treatment strategies. Many common themes are described throughout the literature
      regarding patient risk factors, testing, prevention,diagnosis, and treatment of
      RCM allergic-type reactions. LIMITATIONS: The current review did not perform a
      meta-analysis of the available data, as most of the available articles were
      trials that were randomly controlled. Therefore, the conclusions of the present
      article are general, and qualitative in nature. CONCLUSION: Although the
      mechanisms of various RCM allergic-type reactions are not entirely understood,
      the interventional pain physician should have a basic understanding of patient
      risk factors, prevention, diagnosis, and treatment of these reactions. The
      current review allowed for prevention and treatment strategies for managing
      patients with RCM hypersensitivity reactions.

PMID- 22996861
TI  - Pain in patients with chronic fatigue syndrome: time for specific pain treatment?
AB  - BACKGROUND: Besides chronic fatigue, patients with chronic fatigue syndrome 
      (CFS) have debilitating widespread pain. Yet pain from CFS is often ignored by
      clinicians and researchers. OBJECTIVES: To examine whether pain is a unique
      feature of CFS, or does it share the same underlying mechanisms as other CFS
      symptoms? Second, it is examined whether effective treatments for pain from CFS
      are currently available. STUDY DESIGN: Narrative review covering the scientific
      literature up through December 2011. SETTING: Several universities. RESULTS: From
      the available literature, it is concluded that musculoskeletal factors are
      unlikely to account for pain from CFS. Pain seems to be one out of many symptoms
      related to central sensitization from CFS. This idea is supported by the findings
      of generalized hyperalgesia  (including widespread increased responsiveness to
      painful stimuli) and dysfunctional endogenous analgesia in response to noxious
      thermal stimuli. Pain catastrophizing and depression partly account for pain from
      CFS. Pain increases during exercise is probably due to the lack of endogenous
      analgesia and activation of several genes in response to exercise in CFS. There
      is currently no evidence in support for the efficacy of complementary medicine in
      the treatment of pain from CFS. Intensive education about the biology of pain
      from CFS  (within the framework of central sensitization) has positive short-term
      effects for patients with CFS, and fatigue-targeting cognitive behavioral therapy
      appears to be effective for pain from CFS as well. LIMITATIONS: The role of the
      deficient hypothalamus-pituitary-adrenal axis in relation to pain from CFS, as
      well as the interactions with immune  (dys)functioning require further study.
      CONCLUSION: Recent research has increased our understanding of pain from CFS,
      including its treatment. It is advocated to optimize current CFS treatment
      protocols by targeting the underlying mechanism for those patients having severe
      pain.

PMID- 22996862
TI  - Illicit drug use correlates with negative urine drug test results for prescribed
      hydrocodone, oxycodone, and morphine.
AB  - BACKGROUND: A number of studies indicate that 10.8%-34% of patients with chronic
      pain use illicit drugs. One hypothesis for this occurrence is that some patients
      may be supplementing their prescription medications with illicit drugs.
      OBJECTIVE: The primary purpose of this retrospective data analysis was to test
      the hypothesis that people whose urine specimens are positive for the medications
      that have been listed as being prescribed to them are positive for fewer illicit
      substances than those whose specimens were negative for their prescribed
      medications. The secondary purpose of the study was to correlate the use of
      illicit drugs and the amount of prescribed medications excreted in urine. STUDY
      DESIGN: A retrospective study of the incidence of patients using illicit drugs
      versus their consistency with reported medications. METHODS: Using urine
      specimens from a cohort of nearly 400,000 patients whose identities had been
      redacted, and who were being treated for chronic pain with opioid therapy, this
      study was performed to correlate the patients' positivity with their prescribed
      medication to the prevalence of illicit substance use. A secondary study was
      conducted to correlate the amount of prescribed medication excreted in urine
      (measured in ng/mL) with the incidence of illicit drug use. The specific
      prescription medications analyzed were hydrocodone, morphine, and oxycodone.
      RESULTS: Specimens defined as negative for prescribed hydrocodone (27.3%),
      morphine (11.5%) or oxycodone (19%) were more likely to contain illicit drugs
      than those found to be positive for the prescribed medication. The illicit drug
      prevalence among the inconsistent specimens was 15.3% for hydrocodone, 23.8% for
      morphine, and 24.4% for oxycodone. The secondary study showed no statistically
      significant difference in the excretion level of prescribed medication between
      those patients using and not using illicit drugs. LIMITATIONS: The study is
      limited in that no data was obtained to determine the causal relationships of
      illicit drug use. CONCLUSIONS: This work supports the hypothesis that people who
      are positive for their prescribed medications use fewer illicit drugs than those
      who do not take their medications. It may be beneficial for physicians to test
      more thoroughly for illicit drugs when patients' drug tests are negative for
      their prescribed medications.

PMID- 22996863
TI  - Unreliability of the visual analog scale in experimental pain assessment: a
      sensitivity and evoked potentials study.
AB  - BACKGROUND: Pain is a universal but subjective experience, making it difficult to
      obtain objective information about the experiential dimensions of pain. Although
      the visual analog scale  (VAS) is ubiquitously used in pain assessment, its
      reliability has been questioned. The properties of this rating scale, especially
      its anchor points likely to be reinterpreted by subjects, may bias the results.
      OBJECTIVE: To determine whether the VAS commonly used to assess experimental pain
      is a reliable tool for obtaining objective information about the experiential
      dimensions of pain and to assess whether subjects may erroneously interpret
      anchor points of the classical pain-VAS, ranging from "no pain" to
      "unbearable/worst pain. " STUDY DESIGN: A randomized, controlled prospective
      trial. SETTING: Laboratory of cognitive neurosciences in France. METHODS: Forty
      healthy volunteers were enrolled. We analyzed subjects' ratings of the same high
      intensity  (painful) and low-intensity  (non-painful) thermal laser stimulations
      on 2 computerized VAS during 2 successive sessions: the classical pain-VAS  ("no
      pain" - "unbearable pain") and a pleasantness-VAS  ("very unpleasant" - "very
      pleasant"). Concomitantly, somatosensory evoked potentials  (SEPs) were recorded.
      We investigated the correspondence between these psychophysical measures and
      specific somatosensory evoked potential  (SEP) components elicited by thermal
      stimulation as a function of its intensity. RESULTS: Low-intensity thermal laser
      stimulations rated as painful on the pain-VAS were labeled pleasant on the
      pleasantness-VAS. The cerebral responses following these low-intensity thermal
      stimulations reflected activation of C-fibers, known to convey non-painful warm
      sensations, and not activation of A delta;-fibers, which transmit painful heat
      stimulations. SEP results therefore agreed with subjects' ratings on the
      pleasantness-VAS rather than on the pain-VAS. LIMITATIONS: Study limitations
      include the lack of SEP and psychophysical measures of thermal stimulation
      intensities eliciting a neutral sensation / corresponding to subjects' pain
      threshold. CONCLUSIONS: Taken together, our psychophysical and SEP results
      suggest that healthy individuals reinterpret the "no pain" anchor on the
      classical pain-VAS commonly used in the experimental assessment of pain, by
      rating the intensity of the stimulation rather than pain perception.

PMID- 22996864
TI  - Tissue distribution of clonidine following intraforaminal implantation of
      biodegradable pellets: potential alternative to epidural steroid for
      radiculopathy.
AB  - BACKGROUND: Epidural steroid injections have shown efficacy in short-term pain
      relief, but often require repeated injections in order to provide continued pain
      relief. It has been suggested that a continuous, locally administered dose of an
      anti-inflammatory compound may provide sustained pain relief at doses lower than
      those needed with injections. OBJECTIVE: To evaluate the distribution of
      clonidine after transforaminal placement of a biodegradable drug delivery depot
      system. STUDY DESIGN: A preclinical animal study. METHODS: A biodegradable
      polymer drug depot designed to provide sustained delivery of clonidine was placed
      in or near a single lumbar neural foramen in 12 farm pigs. Clonidine tissue
      concentrations were measured at the implant site and at incremental distances
      from the implant over a time period of 12 weeks. Plasma clonidine levels were
      measured at 4 hours postimplantation on days 1, 2, 3, 5, and 7, and then weekly
      until the termination of the study. RESULTS: Clonidine was detectable up to 6 cm
      away from the drug depot. The highest concentrations of clonidine were present
      within the targeted spinal nerve; the concentration decreased with increasing
      distance from the depot. Clonidine was undetectable in plasma from all animals at
      all time points. LIMITATIONS: While clonidine was detected up to 6 cm from the
      drug depot, it is unknown if the drug concentration has clinical relevance.
      CONCLUSIONS: The results indicate that a biodegradable depot designed to be
      placed in a specific location to provide local sustained release of an anti
      inflammatory and analgesic drug may be a feasible new approach to treat radicular
      pain associated with intervertebral disc pathology and other spinal conditions.

PMID- 22996865
TI  - Utility of intercostal nerve conventional thermal radiofrequency ablations in the
      injured worker after blunt trauma.
AB  - BACKGROUND: Intercostal nerve blocks offer short-term therapeutic relief and
      serve as a diagnostic test for intercostal neuralgia. This original case report
      demonstrates the efficacy of radiofrequency ablations for long-term pain relief
      of intercostal neuralgia. To date, there have been no studies that demonstrate
      the efficacy of thermal conventional intercostal nerve radiofrequency ablations
      for intercostal neuralgia. OBJECTIVE: Describe the use of conventional thermal
      radiofrequency ablations of the intercostal nerves to treat blunt chest wall
      trauma. STUDY DESIGN: Case report. SETTING: Clinical practice. METHODS: Six
      patients suffering from work-related injuries to the chest wall whose treatment
      focused on conventional thermal radiofrequency ablations of the intercostal
      nerves. RESULTS: Four of the 6 patients were pain free by their final visit. The
      remaining 2 patients experienced pain relief until one began wearing a brace
      after an L5-S1 fusion; the other required repeat treatment after 5.5 months.
      LIMITATIONS: Case series. There was limited follow-up as patients were either
      discharged after receiving potentially curative care or were lost to follow-up.
      CONCLUSIONS: Following conventional thermal radiofrequency ablations of the
      intercostal nerves, 5 of the 6 patients experienced either long-term pain relief
      or required no additional care. The treatment has potential efficacy for
      injuries, including rib fractures or intercostal neuralgia, stemming from blunt
      trauma to the chest wall. In addition, there may be a potential for this
      treatment to help patients suffering from postthoracotomy pain.

PMID- 22996866
TI  - Radiofrequency ablation of the supra-orbital nerve in the treatment algorithm of
      hemicrania continua.
AB  - Hemicrania continua  (HC) is an uncommon primary headache disorder in which the
      diagnosis centers on unilaterality and its absolute responsiveness to
      indomethacin. We describe 3 patients with a long standing history of headache
      diagnosed as hemicrania continua. There was profound response to indomethacin
      which was limited by side effects. In one patient the therapy with indomethacin
      was limited secondary to co-morbidities. Initial diagnostic blockade provided
      significant relief of symptoms based on which radio-frequency ablation of the
      supraorbital nerve was performed with substantial improvement in symptoms.
      Traditionally, hemicrania continua has been managed exclusively with oral
      analgesics and is defined by its singular response to indomethacin. Radio
      frequency ablation  (RFA) has been reported in the literature for multiple
      indications. This case series is unique in that it describes 3 patients diagnosed
      with hemicrania continua with pain referred in the supraorbital nerve
      distribution, who underwent radiofrequency ablation of the supraorbital nerve
      with resultant resolution of headaches. Traditionally, hemicrania continua has
      been managed exclusively with oral analgesics and is defined by its singular
      response to indomethacin. This report is unique in that it describes three
      patients diagnosed with hemicrania continua with pain referred in the
      supraorbital nerve distribution who underwent radiofrequency ablation of the
      supraorbital nerve with resultant resolution of headaches. After the RFA medical
      management was minimal to none in both patients. Though the utility and cost
      efficacy of RFA of peripheral nerves needs to be confirmed in well-designed
      trials we present these cases as an example of how this minimally invasive
      technique can safely provide analgesia in a difficult to treat cephalgia.
      Moreover if precise anatomical localization of the headache is possible then
      diagnostic blockade of the appropriate peripheral nerve may be performed followed
      by radiofrequency ablation to provide potentially more sustained analgesia in
      patients where medical management is ineffective or poorly tolerated.

PMID- 22996867
TI  - A minimally invasive surgical technique for the treatment of posttraumatic
      trigeminal neuropathic pain with peripheral nerve stimulation.
AB  - BACKGROUND: Facial pain occurring after traumatic injury of the facial branches
      of the trigeminal nerve is a medical condition that is often very difficult to
      treat. Patients are quite disabled by their symptoms and most therapies are
      ineffective in relieving this pain. Peripheral nerve stimulation has been used as
      a treatment to provide pain relief for this type of intractable atypical facial
      pain. OBJECTIVE: To describe a minimally invasive peripheral nerve stimulation
      surgical technique for treating posttraumatic trigeminal neuralgia. STUDY DESIGN:
      Case report based on a patient seen in a university setting with posttraumatic
      trigeminal neuropathic pain who underwent a minimally invasive technique for the
      placement of a peripheral nerve stimulator. SETTING: University-based outpatient
      clinic. METHODS: A patient with a clinical picture suggestive of trigeminal
      neuropathic pain secondary to trauma involving the V1 and V2 branches of the
      trigeminal nerve was selected. Conservative management was attempted with no
      improvement before peripheral nerve stimulation was tried with a minimally
      invasive surgical technique. We recorded the patient's subjective assessment of
      pain and daily function before and after the procedure. RESULTS: Following the
      procedure, the patient's pain score decreased approximately 50% and the patient
      reported a better quality of life with improvement in daily function as well as a
      more positive outlook on her condition. There were no complications after the
      procedure and the patient reported no complaints with the device. LIMITATIONS:
      Case report. CONCLUSIONS: This surgical technique for placing peripheral nerve
      stimulators allows for a minimally invasive approach for the treatment of
      intractable posttraumatic trigeminal neuralgia with potentially less risk of
      facial nerve damage. This case confirms the need for further studies to be done
      in the future to prove the safety and effectiveness of this technique.

PMID- 22996868
TI  - CT-guided percutaneous vertebroplasty of the upper cervical spine via a
      translateral approach.
AB  - BACKGROUND: The clinical management of spinal hemangiomas and osteolytic
      metastases involving the upper cervical spine  (C1-C3) is challenging. Symptoms
      vary from simple vertebral pain to progressive neurological deficits. Surgery and
      radiotherapy have been the treatment options for years. Surgery, however, can
      result in complications, such as hemorrhage, and may be counter-indicated when
      the treatment goal is primarily palliative due to multiple metastases, an
      unfavorable prognosis and/or a poor performance state. On the other hand,
      radiotherapy carries the risk of inducing secondary sarcomas or producing
      radionecrosis. Percutaneous vertebroplasty  (PVP) was recently introduced as an
      alternative for treating patients in whom surgery and radiotherapy are counter
      indicated. As of yet, there are few PVP case reports. OBJECTIVE: This study aimed
      to evaluate the safety and efficacy of PVP using a computed tomography  (CT)
      guided translateral approach via the space between the carotid sheath and
      vertebral artery for hemangiomas or metastatic lesions at C1-C3 under local
      anesthesia. STUDY DESIGN: CT-guided PVP was performed in 15 patients with
      hemangiomas or metastatic lesions at C1-C3 and clinical outcomes were evaluated.
      SETTING: An interventional therapy group at a medical center in a major Chinese
      city. METHODS: Fifteen consecutive patients had a total of 15 cervical vertebral
      bodies treated with CT-guided PVP via a translateral approach. The patients were
      followed up for a mean postoperative period of 8.3 months  (range, 1-40 months).
      Pain status was assessed using a visual analog scale  (VAS). The presence of
      complications was assessed preoperatively  (baseline) and at 24 hours, 2 weeks,
      and one, 3, 6, 12 and 24 months postoperatively, or until the patient died or was
      lost to follow-up. RESULTS: Fifteen consecutive patients were successfully
      treated with CT-guided PVP via a translateral approach. Their mean VAS score
      decreased from 7.7 +/- 2.9 preoperatively to 1.4 +/- 1.5 by the 24 hour
      postoperative time point, and was 1.2 +/- 1.3 at 2 weeks, 1.2 +/- 1.3 at one
      month, 1.4 +/- 1.3 at 3 months, 0.6 +/- 0.9 at 6 months, 0.3 +/- 0.5 at 12
      months, and 0 at 24 months after the procedure. The mean VAS score at all of the
      postoperative time points differed significantly from the preoperative baseline
      score  (P < 0.05). No severe complications were observed. Mild complications
      included 2 cases  (13.3%) of asymptomatic cement leakage into the epidural space,
      one case  (6.67%) of anterior leakage from the vertebral body, and 2 cases 
      (13.3%) of paravertebral leakage. LIMITATIONS: This was an observational study
      with a relatively small sample size. CONCLUSIONS: The safety and efficacy of CT
      guided PVP using a translateral approach via the space between the carotid sheath
      and vertebral artery were demonstrated in patients with hemangioma or metastasis
      in the upper cervical spine. CT-guided PVP via a translateral approach should
      become a treatment option for such patients.

PMID- 22996869
TI  - Percutaneous osteoplasty for the treatment of a painful osteochondral lesion of
      the talus: a case report and literature review.
AB  - An osteochondral lesion of the talus  (OLT) is a lesion involving the talar
      articular cartilage and its subchondral bone. OLT is a known cause of chronic
      ankle pain after ankle sprains in the active population. The lesion causes deep
      ankle pain associated with weight-bearing, impaired function, limited range of
      motion, stiffness, catching, locking, and swelling. There are 2 common patterns
      of OLTs. Anterolateral talar dome lesions result from inversion and dorsiflexion
      injuries of the ankle at the area impacting against the fibula. Posteromedial
      lesions result from inversion, plantar flexion, and external rotation injuries of
      the ankle at the area impacting against the tibial ceiling of the ankle joint.
      Early diagnosis of an OLT is particularly important because the tibiotalar joint
      is exposed to more compressive load per unit area than any other joint in the
      body. Failure of diagnosis can lead to the evolution of a small, stable lesion
      into a larger lesion or an unstable fragment, which can result in chronic pain,
      joint instability, and premature osteoarthritis.  A 43-year-old man, with a
      history of ankle sprain one year previously, visited our pain clinic for
      continuous right ankle pain after walking or standing for more than 30 minutes.
      There was a focal tenderness on the posteromedial area of the right talus.
      Imaging studies revealed a posteromedial OLT classified as having a geode form
      according to the FOG  (fractures, osteonecroses, geodes) radiological
      classification and categorized as a stage 2a lesion on magnetic resonance
      imaging.  The patient was scheduled for aspiration and osteoplasty with
      hydroxyapatite under arthroscopic and fluoroscopic guidance. A 26-gauge needle
      was inserted to infiltrate local anesthetics into the skin over the cyst and
      ankle joint. An arthroscope was placed into the joint to approach the OLT. The
      arthroscopic view showed that there was no connection between the OLT and the
      cyst of the talus body. A 13-gauge bone biopsy needle was inserted into the cyst,
      and aspiration was performed. Aspirated fluid from the cyst was originally white
      and clear; however, it changed to a blood-tinged, reddish color due to mixing
      with the incisional blood. After aspiration, contrast medium was injected, and
      the shape of the spread was observed. Bone cement comprising hydroxyapatite was
      injected to fill the bone defect of the cyst. A 1.5 mL volume of cement was
      injected into the talus under vigilant fluoroscopic and arthroscopic monitoring
      to prevent its dissemination into the joint. There was no cement leakage into the
      vessels or articular space. Postoperative fluoroscopy and computed tomography
      images showed bone cement filling of the defect. In the present case,
      arthroscopic and fluoroscopic guidance was used for aspiration of an OLT and for
      performing percutaneous osteoplasty with hydroxyapatite for one defect; this
      treatment decreased pain upon weight bearing and enabled a return to work without
      any restrictions one week after the procedure. The purpose of this report was to
      highlight the presence of OLT in chronic ankle pain and to review its management
      strategies.

PMID- 22996870
TI  - Autologous adipose tissue-derived stem cells induce persistent bone-like tissue
      in osteonecrotic femoral heads: not bone-like, but fat-like tissue.

PMID- 22996871
TI  - The effect of epidural resiniferatoxin in the neuropathic pain rat model
      randomized trial: a complementary mechanism.

PMID- 22996872
TI  - [Mortality due to Road Traffic Accidents in Brazil in the last decade: trends and
      risk clusters].
AB  - OBJECTIVE: To analyze the temporal trends of mortality due to Road Traffic
      Accidents (RTA) as well as identify the existence and location of high risk death
      clusters for RTA using spatial analysis. METHODOLOGY: Descriptive study of
      temporal trends by RTA, pedestrians, motorcyclists, motorists and passengers and
      spatial analysis for 2000 and 2010. The data was obtained from the Mortality
      Information System, and standardized rates were calculated by age in Brazilian
      states and municipalities grouped by population size. RESULTS: The mortality
      rates due to RTA between 2000 and 2010 varied from 18 to 22.5 deaths/100,000
      inhabitants. The risk of death for pedestrians decreased in recent years, though
      motorists, motorcyclists and passengers saw a rising trend. A higher risk of
      death by RTA occurred in municipalities with populations up to 20,000 inhabitants
      and in those from 20,000 to 100,000 inhabitants. Spatial analysis revealed risk
      clusters for RTA and motorcyclists and pillion riders with an increase between
      2000 and 2010 and enlargement of the areas most at risk in the Northeast.
      CONCLUSION: Increase in the rates of mortality by RTA mostly in the Northeast.
      Coordinated action between government, civil society and the citizens themselves
      is required to tackle this problem.

PMID- 22996873
TI  - [Are those who die in road accidents any less dead?].

PMID- 22996874
TI  - [Urbanization, globalization and road safety: a potential dialogue in search of
      equity?].

PMID- 22996875
TI  - [Socio-cultural determinants of road traffic accidents (RTC)].

PMID- 22996877
TI  - [Accidents and violence in childhood: survey evidence of emergency care for
      external causes--Brazil, 2009].
AB  - Understanding the characteristics and magnitude of accidents and violence due to
      external causes in children from 0 to 9 years of age is becoming ever more
      important in Public Health. The scope of this paper was to analyze emergency care
      for accidents due to external causes in children. The Sentinel Urgency and
      Emergency Services of the Violence and Accident Vigilance System (VIVA Survey),
      performed in 74 urgency services in the Federal District and 23 State capitals in
      2009 was used. Data of 7,123 children were analyzed: 6,897 (96.7%) victims of
      accidents and 226 (3.3%) of violence. In comparison with victims of violence, the
      visits for accidents were more frequent among white children from 2 to 5 years
      old occurring in the home (p < 0.05). Among the accidents, falls and burns
      predominated in the 0 to 1group, while traffic accidents were most frequent in
      the 6 to 9-year-old age group (p < 0.001). With respect to violence, the visits
      for neglect and physical assault predominated, respectively, in extreme age
      groups, with someone in the family being the perpetrator (p < 0.001). Information
      on the occurrence of external causes in children may support health promotion
      policies, besides guiding health professionals, teachers and families in the
      prevention of such causes.

PMID- 22996878
TI  - [Ecological association between characteristics of the municipalities and the
      risk of homicide in adult males aged 20 to 39 in Brazil: 1999-2010].
AB  - Homicide mortality remains a major public health problem in Brazil, especially
      among young adult males. The aim of this study was to assess the homicide
      mortality risk (HMR) among males aged 20 to 39, and its association with selected
      socio-demographic characteristics of the Brazilian municipalities. This is an
      ecologic study in which all the municipalities in Brazil were the unit of
      analysis. Time trends (from 1999-2002) and adjusted associations between HMR and
      socio-demographic characteristics of municipalities were estimated in a cross
      sectional analysis for 2007-2010 in this study. Between 1999-2002 and 2007-2010,
      an increasing trend of mean HMR rates from 22.7 to 35.5 per 100,000 inhabitants
      was observed in Brazil. In 2007-2010, HMR rates were significantly higher
      (p<0.001) in the largest cities, with higher fertility rates, lower literacy
      rates, higher social inequality (as estimated by the 20/40 income ratio) and more
      urbanized municipalities. Considering the proportion of low income population and
      the average per capita income, associations with HMR identified greater risks in
      the intermediary categories of these independent variables. Findings from this
      study may support the implementation of focal policies directed to more
      vulnerable municipalities.

PMID- 22996879
TI  - [Medical care due to accidental causes in emergency public services--Teresina,
      Piaui--2009].
AB  - Accidents are a major issue in the public health agenda and accidents from
      external causes represent a current challenge for public policies. The scope of
      this article is to describe the characteristics of emergency care grouped in the
      "other accidents" category of the "VIVA" 2009 survey, in the public services of
      Teresina-Piaui. Data was collected from standard forms entered into Epi Info
      3.5.1 and analyzed in Stata 11 (module svy). Characteristics relating to the
      victims, the occurrence and care were compared according to age group and the
      type of accident using the Pearson chi-square test. Of the total of 2,061
      external cause accidents, 677 (32.9%) were due to "other accidents," of which 202
      (29.8%) involved wounds from sharp cutting objects, 172 (25.4%) with objects
      falling on the person or the person hitting an object, 111 (16.4%) with unknown
      objects and 70 (10.3%) with accidents involving animals. Accidents in the
      household with injuries located on the torso leading to hospitalization were
      greater in patients <20 years (p<0,005). Important differences were identified in
      the pattern of the occurrence among the types of accidents. The magnitude of
      these events suggests the need for programs that reduce vulnerability to
      accidents, linking health promotion and prevention actions.

PMID- 22996880
TI  - [Emergency care for victims of violence and accidents: differences in the
      epidemiological profile between the public and private health services. VIVA-
      Campinas, Sao Paulo, Brazil, 2009].
AB  - The scope of this study is to analyze the differences in the profile of emergency
      care for external causes between public and private emergency departments. With
      data come from VIVA-Campinas 2009, the association between the nature of
      healthcare and the characteristics of the victims was verified using the chi
      square test. Using Poisson regression, proportion ratios of care in the public
      and private network were estimated. In the sample of 1094 victims, 67.8% were
      treated by public health. Traffic accidents, animal-related accidents, and
      assaults were 2 times higher in public units, whereas collisions with objects and
      sprains were 75% and 2.7 times higher in private units. Cranium-encephalic
      trauma/polytrauma and cuts/lacerations were 3.8 times and 61% more frequent in
      public care, while victims with no injuries, with dislocations/sprains or
      fractures being predominant in private care. Head and multiple organ injuries,
      road accident and work-related injuries, the use of public transport or mobile
      emergency care services/ambulances were predominant in public care. Revealing
      significant differences in care in public and private care can contribute to the
      organization of healthcare.

PMID- 22996881
TI  - [Accidents by external causes in adolescents: care in sentinel urgency and
      emergency services in the Brazilian State Capitals--2009].
AB  - Adolescents are seeking new references and experiences, which may involve
      attitudes of risk and exposure to accidents and violence from external causes.
      These events constitute a serious Public Health problem. The scope of this study
      was to analyze the occurrence of accidents by external causes in adolescents from
      10 to 19 years of age attended at sentinel urgency and emergency services in
      Brazil. Data from the 2009 Surveillance System for Violence and Accidents (VIVA
      2009) was analyzed in 74 emergency units in 23 state capitals and the Federal
      District. The findings revealed that 6,434 adolescents (89.8%) were victims of
      accidents and 730 (10.2 %) were victims of violence. The main causes of the
      accidents were falls and traffic accidents, and assaults were predominant in
      violence. For both accidents and violence, non-white male adolescents were
      predominant and the events occurred most frequently on the public highways. A
      marked increase was detected, with hospitalization of victims of violence between
      15 and 19 years of age. Understanding the epidemiological reality of external
      causes among adolescents represents an important tool for health prevention and
      promotion policies and the culture of peace seeking to reduce morbidity and
      mortality.

PMID- 22996882
TI  - [Reports of domestic, sexual and other forms of violence against children in
      Brazil].
AB  - The scope of this article is to outline the scenario of domestic, sexual and
      other forms of violence against children (0-9 years old) in Brazil for the year
      2010. It is based on data from reports of domestic, sexual and other forms of
      violence registered with SINAN - Information System for Notifiable Diseases
      (Continuous VIVA). Absolute and relative numbers are presented, derived from
      reported violence, discriminating between children under 1 year of age and those
      between 1-9 years old, due to the specificities that exist in these age groups.
      Throughout the country, the number of reports among those under 10 years of age
      is low (17.1%). Differences were found for the distribution of reports in the
      different Brazilian States. Few municipalities and few services reported violence
      to SINAN-Net in 2010 in the country. Some differences were found between children
      under 1 year of age and those between 1 and 9 years of age, as for instance the
      relationship between the profile of the violence, the victim and the perpetrator,
      and the handling of the case. The quality of the reported information is
      discussed showing the high level of unreported data in some spaces of the
      reporting form. Lack of information may prejudice comprehension of the
      phenomenon, interfering with the planning, organization and operation actions of
      the health services in the country.

PMID- 22996883
TI  - [Accidents and violence among women attended in Sentinel Emergency Services-
      Brazil, 2009].
AB  - Accidents from external causes affect the human population in different ways.
      This article seeks to analyze emergency care for women who are victims of
      accidents and violence. Data from the Surveillance System for Violence and
      Accidents were analyzed. This study was carried out in 74 emergency units of 23
      state capitals and the Federal District in 2009 and included 6,965 women aged
      from 20-59 years. The age groups of 20-39 and 40-59 years were compared for the
      occurrence of accidents and violence. Accidents were more frequent among young
      black women (20-39 years) with more than nine years of schooling. The occurrence
      of violence was also prevalent in young black women but with less schooling.
      Falls were the most frequent accidents (38.6%), followed by traffic accidents.
      The occurrence of violence was more frequent in the home (p <0.000) and the
      mention of alcohol abuse among victims of violence was predominant. The most
      frequent type of violence was aggression (84.6%), in which the aggressor was male
      (79.1%) and identified as an intimate partner (44.1%). It is increasingly
      important that services are able to provide comprehensive and humanized care to
      the victims of this important public health problem.

PMID- 22996884
TI  - [Violence against the elderly: analysis of the reports made in the health sector-
      Brazil, 2010].
AB  - The scope of this study was to describe reports of violence against the elderly
      (e" 60 years) reported in the Information System for Notifiable Diseases - net
      version (Sinan Net) in 2010. We conducted a descriptive, retrospective study with
      data analyzed by Stata version 11. We estimated proportion ratios (PR) of
      violence according to selected variables. Of the 3,593 reports of violence
      against the elderly, 52.3% were against females. Physical violence was
      significantly more frequent against males (PR=0.82) in the group aged 60 to 69
      years, out of the home, committed by offenders who were not sons and were
      suspected of drinking alcohol. Psychological violence was more common among
      elderly people (PR=2.17), in the home, inflicted by sons, with suspected chronic
      alcohol abuse. Negligence was predominant among females (P R=1.24), in the group
      above 70 years of age, in the home, recurrently perpetrated by sons. Sexual
      violence was more common against females (PR=5.21), by offenders who were not
      children, but who consumed alcohol. The knowledge of the different manifestations
      of violence against the elderly supports actions to combat them, identifying
      characteristics of vulnerability in which support networks may intervene.

PMID- 22996885
TI  - [Protection from chronic diseases and the prevalence of risk factors in Brazilian
      state capitals--main results from Vigitel 2010].
AB  - PURPOSE: To describe protection from chronic diseases and the prevalence of risk
      factors with data from a telephone survey in 2010. METHODS: Telephone interviews
      in a random sample of adults living in Brazilian state capitals and the Federal
      District with residential landline telephones. The prevalence of these factors
      was stratified by sex, age and level of education. RESULTS: High prevalence of
      soft drink consumption (28.1%), fatty meat consumption (34.2%), and alcohol abuse
      (18%) and low fruit and vegetable intake (18%) and leisure time physical activity
      (15%) was verified. Approximately half the population was overweight and reported
      no sun protection practices. Physical inactivity and smoking afflicted almost 15%
      of adults. In general, risk factors were more prevalent in men, predominantly
      young adults with lower education levels. CONCLUSION: The results revealed
      differing health behavior according to socio-demographic variables. These
      variables should be taken into consideration in health promotion campaigns.

PMID- 22996886
TI  - [The strengthening of subjects in health management: advances and challenges in
      the experience of Fortaleza, state of Ceara].
AB  - This research deals with the potential and limitations of the strengthening of
      subjects in health management, based on the experience in Fortaleza in the period
      from 2005 to 2008. The subject is approached from a historical-cultural
      standpoint, which considers the dialectical interaction between the individual
      and the collective in deepening human consciousness on the self and the world.
      Focus groups were conducted with managers linked to Primary Healthcare and
      secondary data were utilized. An attempt was made to understand the meaning of
      the narratives constructed using a hermeneutic dialectic approach. Empirical
      categories were identified and analyzed as well as co-intentionality of change,
      political and conceptual drives, human management, reduction of hierarchy,
      fragmentation of work processes and concentration of decision-making power.
      Reflections arose on three main strategic policies: co-management, humanization,
      and continuous health education. It was concluded that, despite the persistence
      of obstacles, in order to improve the quality of healthcare services it is
      essential to establish a democratic management system through organizational
      arrangements and participatory methods that enhance integration and commitment of
      the Unified Health System players (SUS).

PMID- 22996887
TI  - [Reproductive decisions and newborn screening: the perspective of female
      caregivers of children with sickle cell disease].
AB  - One of the goals of the Brazilian Newborn Screening Program created in 2001 was
      to inform couples with the possibility of having children with sickle cell
      diseases regarding reproductive decision-making. This article presents the
      reproductive choices and analyzes the notion of biomedical reproductive risk of
      female caregivers of children with sickle cell disease participating in a newborn
      screening program. Qualitative data collected between 2006 and 2008 was based on
      interviews with 50 female caregivers of children with sickle cell disease
      participating on the Federal District Newborn Screening Program. The research
      revealed the following perceptions underlying reproductive decisions: women who
      want to have other children even with the risk of recurrence of the disease;
      women who do not want to have any more children; and women whose reproductive
      plans are still being considered on the basis of the information provided by the
      newborn screening program. The study revealed that women's reproductive choices
      are based on the experience of child care and self care. The notion of
      reproductive risk is built in order to strengthen women's decisions together with
      their family and other social groups to which they belong.

PMID- 22996888
TI  - [Practices that integrate mental health with public health: matricial support and
      interconsultation].
AB  - This article is an offshoot of my doctoral thesis defended at the Federal
      University of Rio Grande do Sul. It seeks to approach the historical dissociation
      between mental health and broader public health as well as practices that work
      towards the integration of the two. It examines the scientific background that
      fosters this dissociation and also national and international health-related
      documents that stress the need for integration. Based on Rose, I analyzed the
      documents and interviews with health professionals on the practices of Matricial
      Support and Interconsultation formulated by the Ministry of Health and by the
      Porto Alegre/ Rio Grande do Sul Municipal Health Department, which seek to relate
      mental health with Primary Healthcare. These documents and health practices
      propose new subjectivations to the professionals. They emphasize the
      interdisciplinarity and the non-hierarchization of services and knowledge, and
      are in line with the form of contemporary social organization, which suggests
      taking horizontal and democratic decisions, rather than decisions imposed by a
      vertical authority typical of the patriarchal and biomedical model.

PMID- 22996889
TI  - [Dispensing specialized component medicines in areas of the State of Rio de
      Janeiro].
AB  - The Specialized Pharmaceutical Services Component (CEAF) ensures the dispensing
      of high-cost medicines for the treatment of specific diseases. The fact that
      these medicines are mandatory though access is only through legal injunctions,
      suggests flaws in the management of pharmaceutical services. This paper analyzed
      adherence to Clinical Protocols and Therapeutic Guidelines (PCDT) in the
      dispensing of these CEAF medicines. Qualitative research was also conducted in
      facilities with different characteristics in the State of Rio de Janeiro. It was
      noted that the lack of adequate structure in the units studied, including trained
      personnel, compromises the dispensing CEAF medicines in all facilities. The CEAF
      dispensing procedure, heavily dependent on interaction between prescribers and
      dispensers, is not carried out as would be expected. It is possible that
      inadequate performance is also linked to flaws in the planning and organization
      of services. The results indicate barriers in adherence to PCDT by health
      professionals, prejudicing health system users and possibly leading them to
      access medicines by legal means. It is believed that characteristics of the
      investigated facilities are similar to others in Brazil, and the barriers
      identified may be the same, compromising healthcare.

PMID- 22996890
TI  - [Awareness, consumption and access to emergency contraception among female
      university students in the south of the State of Santa Catarina].
AB  - The scope of this study was to investigate knowledge about and access to
      emergency contraception among female university students in the south of the
      State of Santa Catarina. A cross-sectional observational study was conducted
      between September and October 2008, in which a questionnaire was given to 360
      women aged 18 to 45 years. Most belonged to the B2 economic class or higher
      (74.2%) and 79.4% of them had already had intercourse. Of these, 48.6% had used
      emergency contraception, though this was more frequent among younger women.
      Emergency contraception was used 2.4 times, and 87.1% had used contraceptive
      methods within 24 hours after intercourse. Adverse reactions were reported by
      20.9%, the most common being menstrual cycle changes (44.8%) and nausea (44.8%).
      The reasons for using emergency contraception included the lack of condom use
      (44.6%) and condom rupture (39.6%). Of the women interviewed, 15% either failed
      to answer the question on STD prevention or answered incorrectly, while 97.8%
      denied having changed the method used routinely. Only 2.9% of the participants
      had acquired the medication via prescription, and 35.3% received guidance on
      application of the medication at the time of purchase.

PMID- 22996891
TI  - [The working process in the Family Health Strategy and its repercussions on the
      health-disease process].
AB  - This study analyzes the perceptions that health workers engaged in the Family
      Heath Strategy (FHS) of the Federal District (FD) have of their own work process
      and its repercussions on the health-illness process. It is a cross-sectional
      descriptive survey carried out with a sample of 243 FHS/FD workers: 139 community
      health agents, 47 nursing assistants, 41 nurses, and 11 doctors. Four previously
      validated scales were used (Evaluation of Work Context, Human Cost at Work, Pain
      and Pleasure, Work Inventory and Risk of illness). The results revealed a highly
      Taylorised type of work process management typified by a sharp work distinction
      between formulators and performers, highly repetitive work tasks, performance
      supervision and very weak formal communication between the various hierarchical
      levels. These factors have seriously impaired the re-regulation of the work
      process by confronting current objective and subjective realities with pre
      existing norms. In conclusion, the Taylorised work processes, the precarious
      working conditions and the specific difficulties associated with providing care
      to families and communities in their own territories are highly stressful and
      debilitating and underscore the need for improved management of the respective
      work processes.

PMID- 22996892
TI  - Factors associated with the incidence of malaria in settlement areas in the
      district of Juruena, Mato Grosso state, Brazil.
AB  - Factors associated with the incidence of malaria in the Vale do Amanhecer
      settlement, Juruena, Mato Grosso in 2005 were analyzed. Two hundred settlers of
      both genders and aged 18 years and above were interviewed. The prevalence of
      malaria reported in 2005 was 33%. The prevalence ratio showed that the highest
      prevalence of malaria was found in individuals involved in gold mining activities
      (67%); who came from non-endemic areas (43%); had inadequate knowledge about the
      time of greatest activity of the vector (71%); and who reported being outside
      after 5 p.m. (59%). It was concluded that in the Vale do Amanhecer settlement,
      factors such as occupation, origin, inadequate knowledge about where malaria is
      transmitted, inadequate knowledge about the time the mosquito usually bites and
      individual practices in relation to the peak period of mosquito activity were
      associated with malaria in 2005.

PMID- 22996893
TI  - Relations between depression, alcohol and gender in the metropolitan region of
      Sao Paulo, Brazil.
AB  - As part of the GENACIS project, this paper sought to assess the prevalence of
      depression in an urban sample in the city of Sao Paulo, Brazil, as well as the
      association between depression and alcohol abuse according to gender. To achieve
      this, an epidemiological survey was conducted using a stratified probability
      sample, including 2,083 adults. CIDI SF was used to identify depression. The Rao
      Scott test and multivariate logistic regression were used for statistical
      analysis. The response rate was 74.9%. Females (58.3%) under 40 years of age
      (52%) were predominant. The prevalence of depression was 28.3% for women and
      12.7% for men. Most men declared being drinkers (61.1%) in the last year.
      Depression was associated with an alcohol drinking pattern, mostly binge
      drinking, in addition to the occurrence of problems derived from alcohol use.
      Most women declared being abstainers (69.5%). Depression was associated with
      cohabiting with spouses with alcohol-related problems. Results reveal that the
      association between depression and alcohol consumption is distinct between
      genders.

PMID- 22996894
TI  - [Disability, public policies and bioethics: the perception of public
      administrators and legal counselors].
AB  - A descriptive study of the perception of public administrators and counselors
      regarding disability was conducted on the basis of bioethical reflections on
      human rights. The survey involved 50 participants, divided into two groups: 29
      counselors on the rights of disabled people and 21 specialists in public policies
      and government administration. The data obtained was submitted to descriptive
      statistical analysis. In general, the results showed that for counselors
      disability is a social issue and should be shared by society, whereas for public
      administrators it is predominantly a personal tragedy limited to the individual
      and family sphere. It is considered that this differentiated view arises from
      different perspectives regarding the allocation of public resources. It is also
      necessary to stress the importance of living with a disability, or living with
      people with disabilities, to base the assessment of quality and satisfaction with
      life experienced by people with disabilities and contribute to the elaboration of
      public policies. Similar studies with more comprehensive and diversified samples
      are recommended, as well as the adoption of participative and qualitative
      methodologies.

PMID- 22996895
TI  - [Reflections on the management of deinstitutionalization process].
AB  - This study addresses mental health and, based on a conceptual review, offers
      considerations on the management of deinstitutionalization processes regarding
      individuals interned in long-stay psychiatric institutions. Elements concerning
      asylum formation and logic are discussed, along with the mechanisms necessary for
      the effective change in paradigm and practices, with deinstitutionalization and
      psychosocial rehabilitation as the core issues. Reflections are offered regarding
      management actions committed to the psychosocial model, linking such actions to
      the application of the components of care and going beyond the articulation of
      the tools of mental health policy. Theoretical reflection offers suggestions
      referring to the qualification processes of mental health professionals,
      deinstitutionalization in the management of the Unified Health System and
      tripartite action with co-accountability in actions and financing. The final
      considerations recognize the bureaucratic obstacles in the public realm and
      propose facing these challenges as a management challenge, along with processes
      of change that can radically commit to the lives of people, thereby broadening
      the discussion to the ethical realm.

PMID- 22996896
TI  - [Semantic equivalence of the Brazilian Portuguese version of the "Body Change
      Inventory"].
AB  - With the increase in research on the components of Body Image, validated
      instruments are needed to evaluate its dimensions. The Body Change Inventory
      (BCI) assesses strategies used to alter body size among adolescents. The scope of
      this study was to describe the translation and evaluation for semantic
      equivalence of the BCI in the Portuguese language. The process involved the steps
      of (1) translation of the questionnaire to the Portuguese language; (2) back
      translation to English; (3) evaluation of semantic equivalence; and (4)
      assessment of comprehension by professional experts and the target population.
      The six subscales of the instrument were translated into the Portuguese language.
      Language adaptations were made to render the instrument suitable for the
      Brazilian reality. The questions were interpreted as easily understandable by
      both experts and young people. The Body Change Inventory has been translated and
      adapted into Portuguese. Evaluation of the operational, measurement and
      functional equivalence are still needed.

PMID- 22996897
TI  - [Ecological study on the development of health in Brazil].
AB  - The scope of this paper was to assess the health level in Brazilian states using
      the Health Development Index (HDI). The HDI consisted of the following
      dimensions: (1) Health resources: Availability and quality of health resources;
      (2) Primary Healthcare coverage and sanitation; (3) Effectiveness of health
      policies. Each dimension was composed of a set of indicators obtained from
      national databases. In 2005, Brazil had an intermediate level of development of
      health, having progressed from a low level in 1999. Most states had medium and
      low development, with deficits in resources and coverage. The dimension of
      effectiveness was highly developed nationwide. With the construction of a
      synthetic indicator (HDI) it was possible to detect that in most of the country
      there are severe deficiencies in the availability and quality of health
      resources. These results can help health managers to tackle the challenge of
      making public health universal.

PMID- 22996898
TI  - [Mobility and the risk of falls among elderly people of the community of Sao
      Carlos].
AB  - The scope of this study was to assess the mobility and risk of falls among
      elderly people living within the Family Health Strategy area in Sao Carlos and
      identify some factors that have been associated with risks of falls. This is a
      cross-sectional study that presents data from 739 elderly people (mean age of
      69.9 +/- 7.2 years old) registered in the Health and Aging Research Group. Data
      related to sex, age, falls in the last year, mobility using the Timed "Up & Go"
      (TUG) test and cognitive impairment by Mini-Mental State Examination (MMSE), were
      analyzed. Statistical analyses were performed using Chi-square test and Kruskal
      Wallis ANOVA and Mann-Whitney U non-parametric tests. The level of significance
      used for all comparisons was 5% (p < 0.05). Fallers present worse performance to
      TUG than non-fallers (p < 0.001). A higher prevalence of fallers was found among
      women (p < 0.001). No significant association was found between elderly fallers
      and cognitive impairment by MMSE (p = 0.11). Performance in TUG revealed a
      significant difference between the different age groups (p < 0.001). Elderly
      people from Sao Carlos had lower mobility and higher risk of falls in comparison
      with healthy people without chronic disorders and independent for daily living
      activities.

PMID- 22996899
TI  - Quality assessment of the website for eating disorders: a systematic review of a
      pending challenge.
AB  - A Systematic review of articles from peer-reviewed journals was conducted,
      studying the complete texts in all cases. The key words selected were: "Eating
      Disorders" and "Internet." Descriptive analysis was performed on the variables
      selected, and Fisher's Exact test was used to analyze the presence of a linear
      relationship between qualitative variables. Of the 7 studies reviewed, 5 (71.42%)
      focused on content criteria and 2 (28.57%) examined both documentary and content
      criteria. Documentary quality was evaluated using two assessment instruments
      developed by two of the authors, comprising a set of 20 different variables, 5 of
      which were common to both studies (25% observed percentage agreement). Fisher's
      Exact test revealed significant differences between the two questionnaires (p =
      0.049). Studies assessing Website content used 30 different topics to classify
      the subject matter, of which 6 were common to 2 studies. Although generic
      instruments for assessing the quality of Websites devoted to eating disorders
      were found, no validated questionnaire was found. This research did not locate
      any checklist or simple tool which could be used by consumers of health
      information available on the Web.

PMID- 22996900
TI  - [Body dissatisfaction among adolescents: a population-based study].
AB  - The scope of this study was to evaluate body dissatisfaction among adolescents,
      and to explore differences according to sex, socioeconomic status and body mass
      index. 4325 individuals aged 14-15 years old from Pelotas, Brazil, were studied.
      Body dissatisfaction was evaluated comparing the desired image with the perceived
      image, according to the Tiggemann & Wilson-Barret silhouette scale. The
      nutritional status was categorized in accordance with World Health Organization
      criteria, whereas socioeconomic status was evaluated using classifications of the
      Brazilian Association of Research Institutes. It was found that 27.6% of teens
      were overweight. Body dissatisfaction, appraised by the silhouette scale,
      affected 51% of boys and 65.6% of girls. The economic and nutritional status was
      associated with the outcome. Most overweight adolescents wished to have a slimmer
      silhouette than the perceived one. The economic level modified the effect of
      nutritional status on body dissatisfaction. Adolescents from the wealthier
      economic classes who were not in the ideal weight range manifested greater body
      dissatisfaction than the less affluent individuals and, irrespective of economic
      status, girls are more dissatisfied with excess body weight and boys with
      slimness.

PMID- 22996901
TI  - [The contracting of teaching hospitals in the Brazilian Unified Health System].
AB  - This study identifies the potential and limitations of contracting to improve
      health care management, accountability and quality, and expand the participation
      of teaching hospitals in the health service network in the context of the
      Restructuring Program of Teaching Hospitals in the Brazilian Unified Health
      System. It is a case study of four teaching hospitals and their contracting State
      Health Departments. According to the hospital managers, the association is weak
      between contracting and the presence of mechanisms for hospital insertion into
      the health service network with practices and structures for managerial and
      healthcare qualification in the hospital. More structured hospitals in managerial
      and healthcare terms were more structured between contracting and the State
      Health Department. There was an increase in production of medium complexity
      outpatient care and a decrease in primary healthcare procedures. The proposal is
      for ongoing managerial development of the hospital and of the State Health
      Department, review of the operational plan, budgeting, monitoring mechanisms and
      an incentive system, bonding in the teams, among others.

PMID- 22996902
TI  - [Social inequality and epidemiological studies: a reflection].
AB  - Social indicators are now indispensable in the list of variables of
      epidemiological studies, based on the fact that the determination of health
      complaints is complex and multidimensional. From this perspective, social
      inequality has gained prominence as an explanatory factor for the health
      conditions of populations. The scope of this article is to discuss the different
      concepts that underpin the selection of the indicators used in epidemiological
      studies and examine the psychosocial effects on human beings caused by social
      inequality. A literature review of epidemiological studies that used social
      inequality and social capital indicators was conducted for a better understanding
      of health problems, as well as an investigation in the fields of sociology and
      social psychology. The research revealed that there is some controversy
      surrounding the effect of social inequality on health, possibly because these
      indicators are predominantly based on income and individual consumption capacity.
      Likewise, social capital indicators at cognitive and structural levels are too
      limited to understand the dynamism of social relations. Accordingly, further
      studies are needed for the construction of social indicators capable of examining
      the complexity of modern societies.

PMID- 22996903
TI  - [Patients from a reference center for leprosy: Rio de Janeiro and Duque de
      Caxias, 1986-2008].
AB  - The scope of this study was to compare epidemiological data on leprosy patients
      living in two cities with different socioeconomic and endemic profiles that were
      monitored in a single center of reference. A descriptive study was made of data
      from patients in the Souza Araujo Outpatient facility treated in the period 1986
      2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de
      Caxias (n = 336). RESULTS: Among patients from Duque de Caxias, in comparison
      with patients from Rio de Janeiro, there was a higher proportion of cases: below
      the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and
      cases detected through surveillance of contacts. Patients in Duque de Caxias had
      lower average incomes and education levels. There were no statistically
      significant differences regarding gender, disability level, reaction in the
      diagnosis, final BI, bandonment and regularity of treatment. The differences
      found between the patients monitored in a single center of reference, could be
      partly related to contextual differences between the municipalities. On the other
      hand, it was observed that the provision of treatment and monitoring can minimize
      the effect of different contextual factors on health outcomes.

PMID- 22996904
TI  - [The frontiers of medicalization: tensions surrounding the identification and
      appreciation of child malnutrition in a primary healthcare center of the city of
      Buenos Aires].
AB  - The medicalization of life and its implications for the production of
      subjectivities are phenomena that have been highlighted by the human sciences in
      the study of health and disease. Nevertheless, the analysis of its local
      expressions has been insufficiently covered. The scope of this paper is to
      explore this field by an ethnographical study of the medicalization process of
      child malnutrition in a primary healthcare center of the city of Buenos Aires. We
      will describe analytically the singularities involved in the body perception and
      the alimentary context by health professionals and their patients. We emphasize
      that the criteria of perception and moral values that encourage social positions
      of health professionals and recipients of their actions precluded the
      institutionalization of a medical vision. We conclude that the process analyzed
      highlights the need to exceed the medicalization approaches dealing exclusively
      from the angle of imposition. The social history of the groups involved and ways
      of establishing relationships in local settings, are essential to understand the
      peculiarities of these processes.

PMID- 22996907
TI  - Quantitative and sensitive protein detection strategies based on aptamers.
AB  - Aptamers are functional oligonucleotides of single-stranded RNA or DNA that can
      selectively recognize their targets with high affinity. Hence, they have been
      widely developed for analytical, diagnostic, and therapeutic applications. In
      this review, we have summarized recent advances in the development of aptamer
      based detection systems. Aptamers can be amplified exponentially by PCR, which is
      one of the advantages of aptamers over antibodies. Recently, we have developed
      immuno-aptamers that bind to mouse or rabbit IgG and constructed a novel
      sensitive detection system based on a conventional ELISA, called the immuno
      aptamer PCR assay. In this article, the aptamer-based ready-to-use sensors and
      another PCR-based aptamer assays are also described; moreover, we have discussed
      highly sensitive aptamer-based detection systems.

PMID- 22996909
TI  - Ultrafast photoinduced energy and electron transfer in multi-modular donor
      acceptor conjugates.
AB  - New multi-modular donor-acceptor conjugates featuring zinc porphyrin (ZnP),
      catechol-chelated boron dipyrrin (BDP), triphenylamine (TPA) and fullerene
      (C(60)), or naphthalenediimide (NDI) have been newly designed and synthesized as
      photosynthetic antenna and reaction-center mimics. The X-ray structure of
      triphenylamine-BDP is also reported. The wide-band capturing polyad revealed
      ultrafast energy-transfer (k(ENT) =1.0 * 10(12) s(-1)) from the singlet excited
      BDP to the covalently linked ZnP owing to close proximity and favorable
      orientation of the entities. Introducing either fullerene or naphthalenediimide
      electron acceptors to the TPA-BDP-ZnP triad through metal-ligand axial
      coordination resulted in electron donor-acceptor polyads whose structures were
      revealed by spectroscopic, electrochemical and computational studies. Excitation
      of the electron donor, zinc porphyrin resulted in rapid electron-transfer to
      coordinated fullerene or naphthalenediimide yielding charge separated ion-pair
      species. The measured electron transfer rate constants from femtosecond transient
      spectral technique in non-polar toluene were in the range of 5.0 * 10(9)-3.5 *
      10(10) s(-1). Stabilization of the charge-separated state in these multi-modular
      donor-acceptor polyads is also observed to certain level.

PMID- 22996910
TI  - Inherited long QT syndrome: clinical manifestation, genetic diagnostics, and
      therapy.
AB  - Inherited long QT syndrome (LQTS) is characterized by a prolonged ventricular
      repolarization (QTc interval) and symptoms (syncope, sudden cardiac arrest) due
      to polymorphic ventricular arrhythmias. As of today, 13 different cardiac ion
      channel genes have been associated with congenital LQTS. The most common ones are
      due to KCNQ1 (LQT-1), KCNH2 (LQT-2), and SCN5A (LQT-3) gene mutations and account
      for up to 75 % of cases. Typical clinical findings are an increased QT interval
      on the surface electrocardiogram, specifically altered T wave morphologies,
      polymorphic ventricular arrhythmias, or an indicative family history. Recently,
      in the HRS/EHRA expert consensus statement, comprehensive genetic testing of
      major LQTS genes was recommended for index patients for whom there is a strong
      clinical suspicion of LQTS. Overall, antiadrenergic therapy, in particular beta
      receptor blockers, has been the mainstay of therapy and has significantly reduced
      cardiac events. For high-risk patients, an implantable cardioverter defibrillator
      (ICD) is recommended. Importantly, lifestyle modification and avoidance of
      arrhythmia triggers are additional important approaches.

PMID- 22996911
TI  - Phillip V. Tobias as an anatomist.
AB  - The article outlines the career of the renowned South African scientist Phillip
      Vallentine Tobias. While he made substantial contributions to a number of
      scientific disciplines, Tobias spent most of his career teaching anatomy at his
      alma mater, University of the Witwatersrand, Johannesburg, and saw himself
      primarily as an anatomist. The first part of this article presents Tobias' major
      contributions to science and demonstrates that his profound knowledge of anatomy
      was the basis of many of his groundbreaking research accomplishments. The second
      part of the article focuses on Tobias' career in anatomy and his significant
      contribution to anatomy teaching and administration, particularly in establishing
      and organizing the Anatomical Society of Southern Africa. The article also
      demonstrates how Tobias' academic career was constrained by the oppressive system
      of apartheid South Africa and how social engagement was an integral part of his
      intellectual activities.

PMID- 22996912
TI  - Proton affinity of para-substituted acetophenones in gas phase and in solution: a
      theoretical study.
AB  - The gas phase proton affinities PA and basicities GB for a series of para
      substituted acetophenones weak bases (B) p.X-C(6)H(4)CO*CH(3) with X=H, F, Cl,
      Br, I, Me, CF(3), CN, NO(2), OCH(3), NH(2), CH(2)OH, N(CH(3))(2), OH, [Formula:
      see text], ... have been calculated at 298.15 K at the density functional theory
      DFT/B3LYP level with a 6-311++G (2d,2p) basis set. Conformational results lead to
      only one stable planar conformer for both unprotonated compounds and their O*
      protonated forms. Satisfactory accuracy and computational efficiency could be
      reached if the computed PAs are scaled by a factor 0.983. Protonation at more
      than one site is discussed and the carbonyl oxygen atom is found to be the
      preferential protonated site rather than the substituent X. The calculated gas
      phase PAs show a good agreement with the experimental available data. The
      electron-donating/electron-withdrawing nature of the substituents has an enormous
      influence upon the thermochemical and structural properties. The influence of
      environment on the proton affinity has been studied by means of SCRF solvent
      effect computations using PCM solvation model for two solvents: water and
      SO(2)CI(2). Confrontation between computed and experimental pK(B) values exhibits
      better agreement in aqueous solution than in organic solvent.

PMID- 22996913
TI  - Polyoxazolines for nonfouling surface coatings--a direct comparison to the gold
      standard PEG.
AB  - The prevention of surface fouling is becoming increasingly important for the
      development of anti-infective medical implants, biosensors with improved signal
      to-noise ratios, and low-fouling membranes to name a few examples. We review a
      direct comparison of poly(ethylene glycol), the gold standard polymer to impart
      surfaces with nonfouling properties, to an alternative polymer, poly(2-methyl-2
      oxazoline) (PMOXA), and show that both polymers are equally excellent in
      rendering surfaces nonfouling while PMOXA coatings are more stable in oxidative
      environments. We discuss prerequisites for the fabrication of nonfouling surface
      coatings and implications for the polymer choice according to application
      requirements.

PMID- 22996908
TI  - The myofibroblast matrix: implications for tissue repair and fibrosis.
AB  - Myofibroblasts, and the extracellular matrix (ECM) in which they reside, are
      critical components of wound healing and fibrosis. The ECM, traditionally viewed
      as the structural elements within which cells reside, is actually a functional
      tissue whose components possess not only scaffolding characteristics, but also
      growth factor, mitogenic, and other bioactive properties. Although it has been
      suggested that tissue fibrosis simply reflects an 'exuberant' wound-healing
      response, examination of the ECM and the roles of myofibroblasts during
      fibrogenesis instead suggest that the organism may be attempting to recapitulate
      developmental programmes designed to regenerate functional tissue. Evidence of
      this is provided by the temporospatial re-emergence of embryonic ECM proteins by
      fibroblasts and myofibroblasts that induce cellular programmatic responses
      intended to produce a functional tissue. In the setting of wound healing (or
      physiological fibrosis), this occurs in a highly regulated and exquisitely
      choreographed fashion which results in cessation of haemorrhage, restoration of
      barrier integrity, and re-establishment of tissue function. However, pathological
      tissue fibrosis, which oftentimes causes organ dysfunction and significant
      morbidity or mortality, likely results from dysregulation of normal wound-healing
      processes or abnormalities of the process itself. This review will focus on the
      myofibroblast ECM and its role in both physiological and pathological fibrosis,
      and will discuss the potential for therapeutically targeting ECM proteins for
      treatment of fibrotic disorders.

PMID- 22996914
TI  - Separate and overlapping relationships of inattention and
      hyperactivity/impulsivity in children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - There is debate regarding the dimensional versus categorical nature of attention
      deficit/hyperactivity disorder (ADHD). This study utilized confirmatory factor
      analysis to examine this issue. ADHD symptoms rated on interviews and rating
      scales from a large sample of individuals (ages 3-17, 74 % male, 75 % Caucasian)
      with ADHD were examined (n = 242). Four potential factor structures were tested
      to replicate prior findings in a sample with a wide age range and included only
      participants who met DSM-IV-TR diagnostic criteria for ADHD. Correlations with
      executive function measures were performed to further assess the separability and
      validity of the derived factors. The data support a bifactor model with a general
      ADHD factor and two specific factors, inattention and hyperactivity/impulsivity.
      Importantly, the individual factors were also differentially correlated with
      executive functioning measures. This study adds to a growing literature
      suggesting both a general component to ADHD, as well as dimensional traits of
      inattention and hyperactivity/impulsivity, associated with distinct executive
      functioning profiles. The presence of a general underlying factor contraindicates
      separating the inattentive and combined subtypes of ADHD into distinct disorders.

PMID- 22996915
TI  - The multiple Tudor domain-containing protein TDRD1 is a molecular scaffold for
      mouse Piwi proteins and piRNA biogenesis factors.
AB  - Piwi-interacting RNAs (piRNAs) are small noncoding RNAs expressed in the germline
      of animals. They associate with Argonaute proteins of the Piwi subfamily, forming
      ribonucleoprotein complexes that are involved in maintaining genome integrity.
      The N-terminal region of some Piwi proteins contains symmetrically dimethylated
      arginines. This modification is thought to enable recruitment of Tudor domain
      containing proteins (TDRDs), which might serve as platforms mediating
      interactions between various proteins in the piRNA pathway. We measured the
      binding affinity of the four individual extended Tudor domains (TDs) of murine
      TDRD1 protein for three different methylarginine-containing peptides from murine
      Piwi protein MILI. The results show a preference of TD2 and TD3 for consecutive
      MILI peptides, whereas TD4 and TD1 have, respectively, lower and very weak
      affinity for any peptide. The affinity of TD1 for methylarginine peptides can be
      restored by a single-point mutation back to the consensus aromatic cage sequence.
      These observations were confirmed by pull-down experiments with endogenous Piwi
      and Piwi-associated proteins. The crystal structure of TD3 bound to a methylated
      MILI peptide shows an unexpected orientation of the bound peptide, with
      additional contacts of nonmethylated residues being made outside of the aromatic
      cage, consistent with solution NMR titration experiments. Finally, the molecular
      envelope of the four tandem Tudor domains of TDRD1, derived from small angle
      scattering data, reveals a flexible, elongated shape for the protein. Overall,
      the results show that TDRD1 can accommodate different peptides from different
      proteins, and can therefore act as a scaffold protein for complex assembly in the
      piRNA pathway.

PMID- 22996916
TI  - Correlation of sonographic features of invasive ductal mammary carcinoma with
      age, tumor grade, and hormone-receptor status.
AB  - PURPOSE: To determine whether presenting sonographic features of invasive ductal
      carcinomas (IDC) are associated with patient age, tumor histologic grade, and
      hormonal receptor status. METHODS: Sonographic features of 101 consecutive cases
      of IDC seen at ultrasound were retrospectively assessed based on the BI-RADS
      criteria of posterior acoustic appearance, tumor margins, and echogenicity.
      Associations between sonographic features and tumor characteristics were
      statistically evaluated with attention to patient age. RESULTS: IDC with
      shadowing compared with unchanged posterior acoustic appearance were
      significantly more likely to be of low histologic grade (Odds Ratio [OR] = 5.00;
      p < 0.05) and estrogen receptor (ER) -positive (OR = 10.00; p < 0.05).
      Conversely, posterior enhancement was associated with ER-negative status (OR =
      4.45; p < 0.01), particularly among patients younger than 60 years of age (OR =
      5.36, p < 0.05). Circumscribed tumors were more often high grade, particularly
      among older women (p < 0.01), and hormone receptor--negative regardless of age
      group. Among older women, tumors with mixed echogenicity tended to be high grade
      and progesterone receptor--negative (p values < 0.05). Noncircumscribed borders
      were observed for all tumors with posterior shadowing, and 97% of such tumors
      were also ER positive. CONCLUSIONS: Sonographic features were significantly
      associated with tumor grade and hormone receptor status, with some differences
      based on patient age. Specifically, the presence of posterior shadowing was
      associated with lower histologic grade and ER-positive status, especially in
      older patients. In contrast, we found that posterior acoustic enhancement was
      more commonly associated with ER-negative status, especially in younger patients.

PMID- 22996918
TI  - Concise review: The Piwi-piRNA axis: pivotal beyond transposon silencing.
AB  - Piwi proteins and their associated piRNAs are essential for preserving the self
      renewal property of mammalian germ stem cells. Their highly conserved role in CpG
      island DNA methylation and chromatin modifications in germ stem cells has long
      been associated with transposon silencing but recent reports hint at protein
      coding regions being targets for Piwi-mediated epigenetic changes as well.
      Interestingly, the expression of PIWI family members is not restricted to the
      germline, and certain members have also been implicated in tumorigenesis in cases
      of adenocarcinomas, gliomas, and sarcomas. The following review discusses our
      knowledge of the function of Piwi proteins and piRNAs in suppressing transposable
      elements while maintaining the self-renewing population of germ stem cells. We
      also highlight the somatic function of Piwi as an epigenetic modifier.
      Furthermore, we summarize the recently uncovered involvement of Piwi proteins and
      piRNAs in various cancers.

PMID- 22996917
TI  - Cathepsin D acts as an essential mediator to promote malignancy of benign
      prostatic epithelium.
AB  - BACKGROUND: Stromal-epithelial interactions are important in both development and
      prostate cancer. Stromal changes have been shown to be powerful prognostic
      indicators of prostate cancer progression and of patient death helping to define
      lethal versus indolent phenotypes. The specific molecular underpinnings of these
      interactions are incompletely understood. We investigated whether stromal
      cathepsin D (CathD) overexpression affects prostate tumorigenesis through a
      paracrine mechanism. METHODS: Normal prostate fibroblasts (NPF) were retrovirally
      transduced to overexpress cyclin D1 (CD1) and were designated NPF(CD1) .
      Cathepsin D expression was knocked down using shRNA in cancer associated
      fibroblasts (CAF) and NPF(CD1) . We analyzed these stromal cell lines using
      immunohistochemistry, Western blot, and tissue recombination. RESULTS: An
      examination of human prostate tissue revealed significantly increased stromal
      staining of CathD in malignant prostate tissue. Overexpression of CD1 in normal
      prostate fibroblasts (NPF(CD1) ) produced a phenotype similar to, but more
      moderate than, CAF in a tissue recombination model. Knockdown studies revealed
      that CathD is required for NPF(CD1) motility and invasive growth in vitro. BPH-1
      cell proliferation was found to be induced when cultured with NPF(CD1)
      conditioned medium, this effect was inhibited when CathD was knocked down in
      NPF(CD1) cells. Overexpression of CathD in prostate stromal cells induced
      malignancy in adjacent epithelium, and this transformation was inhibited when
      stromal CathD expression was knocked down in CAF. CONCLUSIONS: The study
      presented here demonstrates increased CathD expression is seen in human CAF. The
      upregulation of CD1 results in concomitant increases in CathD expression.
      Elevated CathD expression in the stroma contributes to tumor promotion.

PMID- 22996919
TI  - Cath lab accreditation: our ACE in the hole.

PMID- 22996920
TI  - Has the gender gap in percutaneous coronary intervention-related mortality
      narrowed?

PMID- 22996921
TI  - Periprocedural myocardial infarction: it's the plaque, not the stent.

PMID- 22996922
TI  - Nano version of the XIENCE stent: good things may come in small packages.

PMID- 22996923
TI  - Where's the dose?

PMID- 22996924
TI  - "Wanted: dead or alive?" A novel use of FFR theory to assess myocardial viability
      after STEMI.

PMID- 22996925
TI  - Guilt by association: after enhanced interrogation, the data yield a confession.

PMID- 22996926
TI  - How treating a chronic total occlusion fffirms that "necessity is the mother of
      all inventions".

PMID- 22996927
TI  - Size does not matter.

PMID- 22996928
TI  - Treatment of aortoiliac chronic total occlusions: guidelines and reality.

PMID- 22996929
TI  - An olympic challenge: deconstructing a once useful "Bird's Nest".

PMID- 22996930
TI  - No good deed goes unpunished: persistent interatrial septal defect after
      transcatheter transseptal therapy.

PMID- 22996931
TI  - Antegrade approach for percutaneous valve implantation.

PMID- 22996933
TI  - Circular suture ligation of presacral venous plexus to control presacral venous
      bleeding during rectal mobilization.
AB  - BACKGROUND: Presacral venous bleeding during rectal mobilization is uncommon but
      potentially life-threatening. Various methods have been proposed for controlling
      the bleeding, but each has some obvious limitations in clinical practice. We
      report a simple technique that was designated as circular suture ligation. This
      technique was efficient in controlling presacral venous bleeding encountered
      during rectal mobilization. METHODS: The key point of circular suture ligation
      was to control the bleeding by suture ligating the venous plexus in one or more
      circles in the area with intact presacral fascia that surrounds the bleeding site
      while the bleeding site was temporarily controlled with fingertip pressure. From
      September 2007 to December 2011, 258 patients underwent rectal surgery in our
      department because of rectal cancer. Uncontrolled presacral venous bleeding with
      traditional methods was encountered in eight patients (3 %) with estimated blood
      loss from 300 to 5,000 ml. RESULTS: Bleeding was successfully controlled in all
      eight patients with the circular suture ligation. None of the patients required
      reoperation for bleeding or other issues. No patients developed chronic pelvic
      pain after the operation. CONCLUSIONS: Our experience suggests that circular
      suture ligation of venous plexus in the area with intact presacral fascia that
      surrounds the bleeding site is an effective and simple technique to control
      presacral venous bleeding when traditional techniques fail.

PMID- 22996932
TI  - Dual imaging and photoactivated nanoprobe for controlled cell tracking.
AB  - A photoactivated nanoprobe for cell labeling and tracking is demonstrated. The
      nanoprobe enables all targeted cells to be imaged (at 680 nm) as well as specific
      cells to be photoactivated using 405 nm light. Photoactivated cells can then be
      tracked (at 525 nm) spatiotemporally in a separate channel over prolonged
      periods.

PMID- 22996934
TI  - Using ALPPS to induce rapid liver hypertrophy in a patient with hepatic fibrosis
      and portal vein thrombosis.

PMID- 22996935
TI  - Nanometer-sized alumina packed microcolumn solid-phase extraction combined with
      field-amplified sample stacking-capillary electrophoresis for the speciation
      analysis of inorganic selenium in environmental water samples.
AB  - In this paper, a new method of nanometer-sized alumina packed microcolumn SPE
      combined with field-amplified sample stacking (FASS)-CE-UV detection was
      developed for the speciation analysis of inorganic selenium in environmental
      water samples. Self-synthesized nanometer-sized alumina was packed in a
      microcolumn as the SPE adsorbent to retain Se(IV) and Se(VI) simultaneously at pH
      6 and the retained inorganic selenium was eluted by concentrated ammonia. The
      eluent was used for FASS-CE-UV analysis after NH3 evaporation. The factors
      affecting the preconcentration of both Se(IV) and Se(VI) by SPE and FASS were
      studied and the optimal CE separation conditions for Se(IV) and Se(VI) were
      obtained. Under the optimal conditions, the LODs of 57 ng L-1 (Se(IV)) and 71 ng
      L-1 (Se(VI)) were obtained, respectively. The developed method was validated by
      the analysis of a certified reference material of GBW(E)080395 environmental
      water and the determined value was in a good agreement with the certified value.
      It was also successfully applied to the speciation analysis of inorganic selenium
      in environmental water samples, including Yangtze River water, spring water, and
      tap water.

PMID- 22996936
TI  - A heart stopping performance.

PMID- 22996937
TI  - Investigating fertility problems.

PMID- 22996938
TI  - What factors influence prognosis in children with acute cough and respiratory
      tract infection in primary care?

PMID- 22996939
TI  - Improving systems to monitor transmitted HIV drug resistance.

PMID- 22996940
TI  - Flattery will get you everywhere.

PMID- 22996941
TI  - Oncologist is found guilty of misconduct after 27 year old patient dies in trial.

PMID- 22996942
TI  - A label-free mass spectrometry method for relative quantitation of beta-tubulin
      isotype expression in human tumor tissue.
AB  - PURPOSE: Quantitation of beta-tubulin isotype expression in taxane resistant
      human tumor tissue has been difficult to achieve because of the limited
      availability of validated antibodies. Here we present a label-free MS method to
      quantitate relative expression levels of beta-tubulin isotypes. EXPERIMENTAL
      DESIGN: Using isotype-specific reporter peptides, we determined relative beta
      tubulin isotype expression levels in human lung tumor tissue. RESULTS: Four
      reporter peptides were chosen to quantitate the betaI/betaII, betaIV, betaIII,
      and betaV tubulin isotypes. These peptides were validated using human cancer cell
      lines. The label-free method was then used to determine beta-tubulin isotype
      expression in nine human lung tumor samples, which had been described as high or
      low betaIII-tubulin expressing using immunohistochemistry. It was found that
      betaI/betaII (accounting for 18.7-65.7% of total beta-tubulin) and
      betaIVa/betaIVb (26.3-79.1%) were the most abundant isotypes and that the betaIII
      (0-8.9%) and betaV (1.0-10.4%) were less abundant in the tissue. We also
      categorized the samples as high or low betaIII-tubulin expressing. CONCLUSION AND
      CLINICAL RELEVANCE: With this method we can determine the relative expression
      levels of beta-tubulin isotypes in human tumor tissue. This method will
      facilitate studies assessing the use of tubulin isotypes as biomarkers of taxane
      resistance.

PMID- 22996943
TI  - The use of electrospray mass spectrometry to determine speciation in a dynamic
      combinatorial library for anion recognition.
AB  - The composition of a dynamic mixture of similar 2,2'-bipyridine complexes of
      iron(II) bearing either an amide (5-benzylamido-2,2'-bipyridine and 5-(2
      methoxyethane)amido-2,2'-bipyridine) or an ester (2,2'-bipyridine-5-carboxylic
      acid benzylester and 2,2'-bipyridine-5-carboxylic acid 2-methoxyethane ester)
      side chain have been evaluated by electrospray mass spectroscopy in acetonitrile.
      The time taken for the complexes to come to equilibrium appears to be dependent
      on the counteranion, with chloride causing a rapid redistribution of two
      preformed heteroleptic complexes (of the order of 1 hour), whereas the time it
      takes in the presence of tetrafluoroborate salts is in excess of 24 h. Similarly
      the final distribution of products is dependent on the anion present, with the
      presence of chloride, and to a lesser extent bromide, preferring three amide
      functionalized ligands, and a slight preference for an appended benzyl over a
      methoxyethyl group. Furthermore, for the first time, this study shows that the
      distribution of a dynamic library of metal complexes monitored by ESI-MS can
      adapt following the introduction of a different anion, in this case
      tetrabutylammonium chloride to give the most favoured heteroleptic complex
      despite the increasing ionic strength of the solution.

PMID- 22996944
TI  - Employees' negative and positive work-home interaction and their association with
      depressive symptoms.
AB  - BACKGROUND: Depression is the leading cause of disability and high costs
      worldwide. One possibility for preventing depression in the workplace, which has
      received little consideration so far, is the promotion of a successful balance
      between work and personal life. The aim of this study was to investigate
      employees' negative and positive work-home interaction and their association with
      depressive symptoms. METHODS: A cross-sectional study was conducted in the micro-
      and nanotechnology sector in Germany. A stepwise multivariate logistic regression
      analysis was performed using data from N = 213 employees. RESULTS: The results
      suggest that while negative work-home interaction is associated with an increased
      risk for depressive symptoms, positive work-home interaction is correlated with a
      lower risk. Neither positive nor negative interaction in the home-to-work
      direction demonstrated a significant association with depressive symptoms.
      CONCLUSION: When attempting to prevent mental illnesses, such as depression, it
      is important to develop strategies aimed at reducing conflict between work and
      personal life and promoting a positive exchange between these two domains.

PMID- 22996946
TI  - Flow cytometry and immune disorders.

PMID- 22996950
TI  - Synthesis of benzimidazoles by PIDA-promoted direct C(sp2)-H imidation of N
      arylamidines.
AB  - A metal-free synthesis of diversified benzimidazoles from N-arylamidines through
      a phenyliodine(III) diacetate (PIDA) promoted intramolecular direct C(sp(2))-H
      imidation has been developed. The reaction proceeds smoothly at 0  degrees C or
      ambient temperature to provide the desired products in good to excellent yields.
      The synthesis of 2-alkyl- or 2-alkyl-fused benzimidazoles, which are generally
      inaccessible by similar Pd- or Cu-catalyzed approaches, can also be achieved.

PMID- 22996951
TI  - The first generation of beta-galactosidase-responsive prodrugs designed for the
      selective treatment of solid tumors in prodrug monotherapy.
AB  - Massive attack: Galactoside prodrugs have been designed that can be selectively
      activated by lysosomal beta-galactosidase located inside cancer cells expressing
      a specific tumor-associated receptor. This efficient enzymatic process triggers a
      potent cytotoxic effect, releasing the potent antimitotic agent MMAE and allowing
      the destruction of both receptor-positive and surrounding receptor-negative tumor
      cells.

PMID- 22996952
TI  - Colonization by human fibroblasts of polypropylene prosthesis in a composite form
      for hernia repair.
AB  - PURPOSE: Abdominal wall hernia is one of the commonest surgical disorders
      worldwide, and there is no single gold-standard operative technique to repair it.
      In an effort to improve techniques and technologies to reinforce hernia repair,
      synthetic meshes are employed. In this study, a new prosthesis (named composite)
      formed of two polypropylene layers, one macroporous (named mesh) and one
      transparent (named film), was examined to evaluate its capability to enable cell
      proliferation without inducing cell death. Inflammatory processes were also
      examined. METHODS: Human fibroblasts BJ were seeded on multiwells, on which
      composite or film had been placed. After 7, 14, and 21 days, cell growth and
      viability, deposition of collagen, and release of IL-6, IL-1beta, and TNF-alpha
      were evaluated. RESULTS: The "in vitro" protocol showed the composite to be
      colonized by human fibroblasts on the polypropylene macroporous mesh side; no
      cell growth occurred on the film. The slowdown of cell growth observed between 14
      and 21 days was accompanied by an increase in type I collagen deposition and
      marked fibroblast activity. Inflammatory cytokines initially increased, followed
      by their reduction beginning at 14 days. CONCLUSIONS: The new prosthesis
      comprising two polypropylene layers of differing morphologies can be colonized by
      fibroblasts on the side facing the abdominal wall, whereas no cell growth occurs
      on the side facing the viscera. The transient inflammation, observed at early
      experimental times, is probably important for the healing process.

PMID- 22996953
TI  - Immediate hypothermia is not neuroprotective after severe hypoxia-ischemia and is
      deleterious when delayed by 12 hours in neonatal rats.
AB  - BACKGROUND AND PURPOSE: Hypothermia (HT) for neonatal hypoxic-ischemic
      encephalopathy is advised to start within the first 6 hours after birth. There is
      some clinical evidence that HT is more effective against moderate than against
      severe hypoxic-ischemic encephalopathy, but it is unknown whether delayed HT
      beyond 6 hours is effective or even injurious. METHODS: One-hundred seven 7-day
      old rat pups underwent unilateral hypoxia-ischemia of moderate severity. Pups
      were randomized to receive 5 hours of normothermia (NT) or HT starting
      immediately, 3 hours, 6 hours, or 12 hours after the 90-minute hypoxic period.
      One-hundred five 7-day-old rat pups underwent severe hypoxia-ischemia lasting 150
      minutes, followed by the same group design as mentioned. Relative area loss of
      the left/right hemisphere was measured after 1 week of survival. RESULTS: In the
      moderate NT group, the mean area loss of the left hemisphere was 40.5%. The area
      loss was significantly decreased to 24.8% with immediate HT (P<0.05) and
      increased linearly with the delay of HT by 1.788% per hour until at least 6 hours
      of delay (linear regression, P=0.026). After 12-hour delayed HT, the area loss
      was similar to the moderate NT group (41.1%). After severe NT, the mean area loss
      of the left hemisphere was 59.3%. Immediate HT, 3-hour delayed HT, and 6-hour
      delayed HT all resulted in similar area loss, whereas the 12-hour delayed-HT
      resulted in significantly increased area loss (69.5%; P=0.032). CONCLUSIONS:
      Immediate and delayed (<=6 hours) HT provides neuroprotection after moderate
      hypoxia-ischemia in neonatal rats. This neuroprotection decreases linearly with
      increasing delay. After severe insults, however, immediate or delayed HT<=6 hours
      provides no neuroprotection. Twelve-hour delayed hypothermia increased brain
      injury after severe hypoxia-ischemia, which is of clinical concern.

PMID- 22996954
TI  - Diffusion lesion reversal after thrombolysis: a MR correlate of early
      neurological improvement.
AB  - BACKGROUND AND PURPOSE: In acute stroke, diffusion-weighted imaging (DWI) lesions
      are commonly considered markers of irreversible ischemia yet can occasionally
      reverse. However, the extent and clinical correlates of DWI reversal in
      thrombolyzed patients remain unclear. We assessed the extent of reversible acute
      DWI lesions (RADs) and their relationships with clinical outcome in patients
      thrombolyzed<=4.5 hours from onset. METHODS: Data were retrospectively analyzed.
      RAD was defined as an acute DWI lesion not part of a 24-hour DWI lesion as
      determined voxelwise. Associations with an early neurological improvement (early
      neurological improvement=DeltaNational Institutes of Health Stroke Scale>=8 or
      National Institutes of Health Stroke Scale<=2 at 24 hours) or an excellent
      outcome (modified Rankin Scale<=1) were assessed in multivariate analyses.
      RESULTS: One hundred seventy-six patients were included. The median
      (interquartile range) time to treatment from onset was 150 minutes (120-194).
      Eighty-nine patients (50%) exhibited visually-detectable RAD irrespective of its
      extent. Over the whole population, the median percentage and volume of RAD were
      11% (4-36) and 2.4 mL (0.5-8). Subtracting RAD from initial DWI altered perfusion
      weighted imaging-DWI classification in 5 of 100 patients (shift from "no
      mismatch" to "mismatch" profile in all). Percent RAD was significantly greater in
      patients treated<=3 hours (P=0.049), without proximal occlusion (P=0.003), and in
      24-hour recanalizers (P<0.001). Early neurological improvement was independently
      associated with percent RAD. This association increased with percent RAD split in
      quartiles in a "dose-dependent" manner (P for trend=0.01). Excellent outcome was
      independently associated with percent RAD (P for trend<0.001). CONCLUSIONS: DWI
      reversal was often sizeable in patients treated<=4.5 hours. It was strongly
      associated with, albeit not necessarily causal for, early neurological
      improvement.

PMID- 22996955
TI  - The Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and
      Leukoencephalopathy (CADASIL) Scale: a screening tool to select patients for
      NOTCH3 gene analysis.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) phenotype is highly variable, and,
      although the full clinical-neuroimaging picture may be suggestive of the disease,
      no characteristic is pathognomonic. Thus, a genetic test remains the diagnostic
      gold standard, but because it is costly and time-consuming, a pregenetic
      screening appears desirable. We aimed at developing the CADASIL scale, a
      screening tool to be applied in the clinical setting. METHODS: A preliminary
      scale was created assigning weighted scores to common disease features based on
      their frequencies obtained in a pooled analysis of selected international CADASIL
      series. The accuracy of the scale versus the genetic diagnosis was tested with
      receiver operating characteristic analysis after the application of this scale to
      61 CADASIL and 54 NOTCH3-negative patients (no pathogenic mutation on exons 2-23
      of the NOTCH3 gene). To improve the scale accuracy, we then developed an ad hoc
      optimization algorithm to detect the definitive scale. A third group of 39
      patients affected by sporadic small-vessel disease was finally included in the
      algorithm to evaluate the stability of the scale. RESULTS: The cutoff score of
      the definitive CADASIL scale had a sensitivity of 96.7% and a specificity of
      74.2%. This scale was robust to contamination of patients with sporadic small
      vessel disease. CONCLUSIONS: The CADASIL scale is a simple and sufficiently
      accurate screening tool to select patients with a high probability to be affected
      by the disease and therefore to be subjected to the genetic testing.

PMID- 22996956
TI  - External counterpulsation augments blood pressure and cerebral flow velocities in
      ischemic stroke patients with cerebral intracranial large artery occlusive
      disease.
AB  - BACKGROUND AND PURPOSE: External counterpulsation (ECP) is a novel noninvasive
      method used to improve the perfusion of vital organs, which may benefit ischemic
      stroke patients. We hypothesized that ECP may augment cerebral blood flow of
      ischemic stroke patients via induced hypertension. METHODS: We recruited ischemic
      stroke patients with cerebral intracranial large artery occlusive disease and
      healthy elderly controls into this study. Bilateral middle cerebral arteries of
      subjects were monitored using transcranial Doppler. Flow velocity changes before,
      during, and after ECP were, respectively, recorded for 3 minutes while continuous
      beat-to-beat blood pressure data were recorded. Cerebral augmentation index was
      the increase in percentage of middle cerebral artery mean flow velocity during
      ECP compared with baseline. Transcranial Doppler data were analyzed based on
      ipsilateral or contralateral to the infarct side. RESULTS: ECP significantly
      increased mean blood pressure of stroke patients and controls. During ECP, middle
      cerebral artery mean flow velocities of stroke patients increased on both
      ipsilateral and contralateral sides when compared with baseline (ipsilateral
      cerebral augmentation index, 9.64%; contralateral cerebral augmentation index,
      9%; both P<0.001), but there was no increase in difference between the 2 sides
      when compared with each other. Mean flow velocities of controls did not change
      under ECP. After ECP, blood pressure and flow velocity of stroke patients
      returned to baseline level. CONCLUSIONS: ECP provides a new method of cerebral
      blood flow augmentation in ischemic stroke by elevation of blood pressure. Flow
      augmentation induced by ECP suggests the improvement of cerebral perfusion and
      collateral supply from infarct ipsilateral and contralateral sides.

PMID- 22996957
TI  - Migraine and stroke: perspectives for stroke physicians.

PMID- 22996958
TI  - Stroke and cancer: the importance of cancer-associated hypercoagulation as a
      possible stroke etiology.
AB  - BACKGROUND AND PURPOSE: The importance of cancer-associated hypercoagulability as
      a possible stroke etiology in patients with cancer has received relatively little
      attention to date. A recent study has suggested that cancer-associated
      hypercoagulation may be of special importance in the absence of conventional
      stroke mechanisms. METHODS: We identified patients with ischemic stroke
      sequentially admitted to our stroke center with the additional diagnosis of
      active and malignant cancer from 2002 to 2011. By using our prospectively
      collected stroke, MRI, and laboratory data banks, the etiology and risk factors
      of stroke, types of cancer, deep vein thrombosis/pulmonary embolism, d-dimer
      levels, and diffusion-weighted imaging lesion patterns were compared to an age-
      and sex-matched control group. Patients with cancer with a conventional stroke
      etiology and patients with an unidentified and/or cancer-associated stroke
      etiology were analyzed separately. RESULTS: One hundred forty patients with
      cancer and 140 control subjects were included. Unidentified stroke (P<0.001) and
      infarction in multiple vascular territories (P<0.001) were significantly more
      frequent and d-dimer levels significantly higher (P<0.05) in patients with
      cancer. Vice versa, risk factors such as hypertension (P<0.05) and hyperlipidemia
      (P<0.01) were more prevalent in control subjects. Deep vein thrombosis and
      pulmonary embolism were more frequent (P<0.01) and d-dimer levels higher (P<0.01)
      in the patients with unidentified and/or cancer-associated stroke etiology
      compared to the patients with cancer with a conventional stroke etiology. Lung
      and pancreatic cancer were significantly overrepresented and d-dimer levels
      higher in these patients compared with other patients with cancer (P<0.01).
      CONCLUSIONS: Our data confirm the concept of cancer-associated hypercoagulation
      as a widely underestimated important stroke risk factor in patients with cancer,
      especially in those with severely elevated d-dimer levels and in the absence of
      conventional risk factors.

PMID- 22996959
TI  - Risk factors for intracranial hemorrhage in acute ischemic stroke patients
      treated with recombinant tissue plasminogen activator: a systematic review and
      meta-analysis of 55 studies.
AB  - BACKGROUND AND PURPOSE: Recombinant tissue plasminogen activator (rtPA) is an
      effective treatment for acute ischemic stroke but is associated with an increased
      risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for
      ICH with a systematic review of the published literature. METHODS: We searched
      for studies of rtPA-treated stroke patients that reported an association between
      a variable measured before rtPA infusion and clinically important ICH
      (parenchymal ICH or ICH associated with clinical deterioration). We calculated
      associations between baseline variables and ICH with random-effect meta-analyses.
      RESULTS: We identified 55 studies that measured 43 baseline variables in 65 264
      acute ischemic stroke patients. Post-rtPA ICH was associated with higher age
      (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.04), higher stroke
      severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point;
      95% confidence interval, 1.06-1.11), and higher glucose (odds ratio, 1.10 per
      mmol/L; 95% confidence interval, 1.05-1.14). There was approximately a doubling
      of the odds of ICH with the presence of atrial fibrillation, congestive heart
      failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a
      visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of
      the variation in the sizes of the associations among different studies was
      explained by the source of the cohort, definition of ICH, or degree of adjustment
      for confounding variables. CONCLUSIONS: Individual baseline variables were
      modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is
      likely to be difficult if based on single clinical or imaging factors alone.
      These observational data do not provide a reliable method for the
      individualization of treatment according to predicted ICH risk.

PMID- 22996960
TI  - The incidence of cerebral venous thrombosis: a cross-sectional study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the incidence
      of adult cerebral venous thrombosis. METHODS: A retrospective cross-sectional
      study was conducted among all 19 hospitals located in 2 Dutch provinces serving
      3.1 million people. Adult cerebral venous thrombosis cases diagnosed between
      January 1, 2008, and December 31, 2010, were identified using the Dutch financial
      coding system for hospital care and the International Classification of Diseases,
      9th Revision. Medical records of potential patients were hand searched to
      identify cerebral venous thrombosis cases. The Dutch National Bureau for
      Statistics provided population figures of the 2 provinces during 2008 to 2010.
      RESULTS: Among 9270 potential cases, we identified 147 patients diagnosed with
      cerebral venous thrombosis. Of these, 53 patients did not meet the inclusion
      criteria; therefore, 94 patients were included in the analysis. The overall
      incidence was 1.32 per 100 000 person-years (95% CI, 1.06-1.61). Among women
      between the ages of 31 and 50 years, the incidence was 2.78 (95% CI, 1.98-3.82).
      CONCLUSIONS: The incidence of cerebral venous thrombosis among adults is probably
      higher than previously believed.

PMID- 22996961
TI  - Clonal evolution of high-grade serous ovarian carcinoma from primary to recurrent
      disease.
AB  - High-grade serous carcinoma (HGSC) is the most common and fatal form of ovarian
      cancer. While most tumours are highly sensitive to cytoreductive surgery and
      platinum- and taxane-based chemotherapy, the majority of patients experience
      recurrence of treatment-resistant tumours. The clonal origin and mutational
      adaptations associated with recurrent disease are poorly understood. We performed
      whole exome sequencing on tumour cells harvested from ascites at three time
      points (primary, first recurrence, and second recurrence) for three HGSC patients
      receiving standard treatment. Somatic point mutations and small insertions and
      deletions were identified by comparison to constitutional DNA. The clonal
      structure and evolution of tumours were inferred from patterns of mutant allele
      frequencies. TP53 mutations were predominant in all patients at all time points,
      consistent with the known founder role of this gene. Tumours from all three
      patients also harboured mutations associated with cell cycle checkpoint function
      and Golgi vesicle trafficking. There was convergence of germline and somatic
      variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle
      pathways. The vast majority of somatic variants found in recurrent tumours were
      present in primary tumours. Our findings highlight both known and novel pathways
      that are commonly mutated in HGSC. Moreover, they provide the first evidence at
      single nucleotide resolution that recurrent HGSC arises from multiple clones
      present in the primary tumour with negligible accumulation of new mutations
      during standard treatment.

PMID- 22996962
TI  - Anatomy of female puberty: The clinical relevance of developmental changes in the
      reproductive system.
AB  - Puberty is the period of biologic transition from childhood to adulthood. The
      changes that occur at this time are related to the increasing concentrations of
      sex steroid hormones. In females, most pubertal changes are caused by estrogen
      stimulation that results from the onset of central puberty. Significant
      development occurs in the organs of the female reproductive system and results in
      anatomic changes that characterize reproductive maturity. Adrenal and ovarian
      androgens also increase during puberty, affecting change that includes the
      promotion of certain secondary sex characteristics. The ability to recognize
      normal pubertal anatomy and distinguish between estrogen and androgen effects is
      important in the ability to diagnose and treat disorders of sex development,
      precocious puberty, pubertal delay, and menstrual irregularities in children and
      adolescents. An understanding of this developmental process can also help
      clinicians identify and treat reproductive pathology in adults and across all
      female life stages.

PMID- 22996963
TI  - Localization of cholesterol, amyloid and glia in Alzheimer's disease transgenic
      mouse brain tissue using time-of-flight secondary ion mass spectrometry (ToF
      SIMS) and immunofluorescence imaging.
AB  - The spatial distributions of lipids, amyloid-beta deposits, markers of neurons
      and glial cells were imaged, at submicrometer lateral resolution, in brain
      structures of a mouse model of Alzheimer's disease using a new methodology that
      combines time-of-flight secondary ion mass spectrometry (ToF-SIMS) and confocal
      fluorescence microscopy. The technology, which enabled us to simultaneously image
      the lipid and glial cell distributions in Tg2576 mouse brain structures, revealed
      micrometer-sized cholesterol accumulations in hippocampal regions undergoing
      amyloid-beta deposition. Such cholesterol granules were either associated with
      individual amyloid deposits or spread over entire regions undergoing
      amyloidogenesis. Subsequent immunohistochemical analysis of the same brain
      regions showed increased microglial and astrocytic immunoreactivity associated
      with the amyloid deposits, as expected from previous studies, but did not reveal
      any particular astrocytic or microglial feature correlated with cholesterol
      granulation. However, dystrophic neurites as well as presynaptic vesicles
      presented a distribution similar to that of cholesterol granules in regions
      undergoing amyloid-beta accumulation, thus indicating that these neuronal
      endpoints may retain cholesterol in areas with lesions. In conclusion, the
      present study provides evidence for an altered cholesterol distribution near
      amyloid deposits that would have been missed by several other lipid analysis
      methods, and opens for the possibility to study in detail the putative liaison
      between lipid environment and protein structure and function in Alzheimer's
      disease.

PMID- 22996964
TI  - Selenium/Tellurium-Containing Hyperbranched Polymers: Effect of Molecular Weight
      and Degree of Branching on Glutathione Peroxidase-Like Activity.
AB  - A series of novel hyperbranched polyselenides and polytellurides with multiple
      catalytic sites at the branching units has been synthesized via the
      polycondensation of A2 + B3 monomers. The GPx-like activities of these polymer
      mimics were assessed and it was found that the polytellurides showed higher GPx
      like activities than the corresponding polyselenides. Interestingly, the polymers
      with higher molecular weights and degree of branching (DB) showed higher GPx-like
      activities than the analogous lower molecular weight polymer. The enhancement in
      the catalytical activity of the hyperbranched polymers with increasing molecular
      weight affirmed the importance of the incorporation of multiple catalytic groups
      in the macromolecule which increases the local concentration of catalytic sites. 

PMID- 22996965
TI  - Carbon nanotubes enhance metastatic growth of lung carcinoma via up-regulation of
      myeloid-derived suppressor cells.
AB  - Metastatic establishment and growth of Lewis lung carcinoma is promoted by single
      walled carbon nanotubes (SWCNT) in C57BL6/J mice. The effect is mediated by
      increased local and systemic accumulation of myeloid-derived suppressor cells
      (MDSC), as their depletion abrogated pro-tumor activity in vivo. These data are
      important for the design of novel theranostics platforms with modules capable of
      depleting or functionally suppressing MDSC to ensure effective immunosurveillance
      in the tumor microenvironment.

PMID- 22996966
TI  - Should intraoperative cell-salvaged blood be used in patients with suspected or
      known malignancy?
AB  - PURPOSE: Intraoperative cell salvage (ICS) is used as an alternative to
      allogeneic blood transfusion in an attempt to avoid or minimize the risks
      associated with allogeneic blood. Intraoperative cell salvage is generally
      avoided in surgeries where malignancy is confirmed or suspected due to concern
      for potential metastasis or cancer recurrence. The application of post-processing
      methods for ICS is hypothesized to eliminate this potential risk. The purpose of
      this narrative review is to examine the in vitro experimental evidence as it
      pertains to the removal of tumour cells from ICS blood and to review the clinical
      studies where ICS blood has been used in patients with malignancy. SOURCE: A
      search of the English literature for relevant articles published from 1973 to
      2012 was undertaken using MEDLINE and Cochrane databases. Bibliographies were
      cross-referenced to locate further studies. PRINCIPAL FINDINGS: Leukoreduction
      filters are an effective method for removal of malignant cells from ICS blood.
      Small non-randomized clinical studies to date do not show evidence of an
      increased rate of metastasis or cancer recurrence. Although a theoretical risk of
      disease recurrence persists, the decision to use autologous ICS blood must be
      weighed against the known risks of allogeneic blood transfusion. CONCLUSION:
      Transfusion of autologous blood harvested via ICS should be considered a viable
      option for reduction or avoidance of allogeneic product during many oncologic
      surgeries and may be a lifesaving option for those patients who refuse allogeneic
      blood products.

PMID- 22996967
TI  - A universal nanoparticle cell secretion capture assay.
AB  - Secreted proteins play an important role in intercellular interactions,
      especially between cells of the immune system. Currently, there is no universal
      assay that allows a simple noninvasive identification and isolation of cells
      based on their secretion of various products. We have developed such a method.
      Our method is based on the targeting, to the cell surface, of heterofunctional
      nanoparticles coupled to a cell surface-specific antibody and to a secreted
      protein-specific antibody, which captures the secreted protein on the surface of
      the producing cell. Importantly, this method does not compromise cellviability
      and is compatible with further culture and expansion of the secreting cells.

PMID- 22996968
TI  - Validation of the 2000 Bernstein-Parsonnet and EuroSCORE at the Heart Institute -
      USP.
AB  - OBJECTIVE: To validate the 2000 Bernstein Parsonnet (2000BP) and additive
      EuroSCORE (ES) to predict mortality in patients who underwent coronary bypass
      surgery and/or heart valve surgery at the Heart Institute, University of Sao
      Paulo (InCor/HC-FMUSP). METHODS: A prospective observational design. We analyzed
      3000 consecutive patients who underwent coronary bypass surgery and/or heart
      valve surgery, between May 2007 and July 2009 at the InCor/HC-FMUSP. Mortality
      was calculated with the 2000BP and ES models. The correlation between estimated
      mortality and observed mortality was validated by calibration and discrimination
      tests. RESULTS: There were significant differences in the prevalence of risk
      factors between the study population, 2000BP and ES. Patients were stratified
      into five groups for 2000BP and three for the ES. In the validation of models,
      the ES showed good calibration (P = 0.596), however, the 2000BP (P = 0.047)
      proved inadequate. In discrimination, the area under the ROC curve proved to be
      good for models, ES (0.79) and 2000BP (0.80). CONCLUSION: In the validation,
      2000BP proved questionable and ES appropriate to predict mortality in patients
      who underwent coronary bypass surgery and/or heart valve surgery at the InCor/HC
      FMUSP.

PMID- 22996969
TI  - Comparison of electrophysiological parameters of septal and apical endocardial
      cardiac stimulation.
AB  - BACKGROUND: The conventional right ventricle (RV) endocardial pacing leads QRS
      widening and desynchronization myocardial compromising ventricular function. With
      the need for stimulation less deleterious, RV septal pacing has been used more.
      Eventually have been reported higher thresholds and smaller R waves in the septal
      stimulation. OBJECTIVE: To compare the parameters of the septal and apical
      stimulation, intra-patient, if there are any differences that may affect the
      choice of the point of stimulation. METHODS: A prospective controlled study. We
      included 25 patients, 67.2+/-9 years, 10 (40%) women with indications for
      pacemaker for bradyarrhythmias. Etiologies were degenerative in nine (36%),
      Coronary disease in eight (32%), Chagas disease in seven (28%), and valve disease
      in one (4%) patient. Electrodes were active fixation and assessed the thresholds
      of command, impedance and R wave in uniand bipolar implant and after six months.
      RESULTS: The average acute threshold command, R wave and impedance unipolar /
      bipolar septais x apicais were respectively 0.73 x 0.73V and 0,74V x 0,78V; 10 x
      9,9mV and 12,3 x 12,4mV; 579 x 621Omega and 611 x 629Omega. Comparisons between
      parameters with septal and apical two-tailed paired t-test showed a P > 0.1.
      After six months, the mean control thresholds, R wave impedances and
      unipolar/bipolar septais x apicais were respectively 0.5V x 0 72V and 0.71V x
      0,87V; 11.4 x 9,5mV and 12x11,2mV; 423x426 Omega and 578x550 Omega, with P >
      0.05, except compared to unipolar pacing threshold septal apical unipolar P 0.02.
      CONCLUSION: Using intra-patient comparisons, no significant differences between
      electrophysiological parameters septal and apical pacing and there are no
      restrictions for choosing the right ventricular septal pacing.

PMID- 22996970
TI  - Preoperative risk factors for mediastinitis after cardiac surgery: analysis of
      2768 patients.
AB  - BACKGROUND: Longitudinal median sternotomy is the most common surgical approach
      for access to heart disease treatment. The deep wound infections in postoperative
      period of cardiovascular surgery are a serious complication requiring high costs
      during treatment. Different studies have indicated some risk factors for the
      development of mediastinitis and preoperative variables are currently under
      investigation. OBJECTIVE: The aim of this study is to identify the preoperative
      risk factors for postoperative development of mediastinitis in patients
      undergoing coronary artery bypass grafting and valve replacement. METHODS: This
      observational study represents a cohort of 2768 consecutive operated patients.
      The period considered for analysis was from May 2007 to May 2009 and there were
      no exclusion criteria. Analysis was performed by univariate and multivariate
      logistic regression model of 38 preoperative variables. RESULTS: Thirty-five
      (1.3%) patients developed mediastinitis and 19 (0.7%) associated with
      osteomyelitis. The patient age average was 59.9 +/- 13.5 years and the EuroSCORE
      of 4.5 +/- 3.6. Hospital mortality was 42.8%. The multivariate analysis
      identified three variables as independent predictors of postoperative
      mediastinitis: intra-aortic balloon pump (OR 5.41, 95% CI [1.83 -16.01], P =
      0.002), hemodialysis (OR 4.87, 95% CI [1.41 to 16.86], P = 0.012) and
      extracardiac vascular intervention (OR 4.39, 95% CI [1.64 to 11.76], P = 0.003).
      CONCLUSION: This study showed that necessity of preoperative hemodynamic support
      with intra-aortic balloon, hemodialysis, and extracardiac vascular intervention
      were risk factors for development of mediastinitis after cardiac surgery.

PMID- 22996971
TI  - Impact of socio-economic profile on the prosthesis type choice used on heart
      surgery.
AB  - BACKGROUND: Valvar heart disease is an important public health problem, more
      common in developing countries, especially in younger. OBJECTIVE: To evaluate the
      epidemiological features of patients and its influence on the prosthesis type
      choice used on patients who underwent valve surgery. METHODS: Cross-sectional.
      Data such as age, sex, provenance, surgery procedure and prosthesis type were
      retrospectively analyzed. We reviewed 366 charts of all patients submitted to
      heart valve surgery during three years in a public health cardiovascular
      treatment center. RESULTS: 52% of patients were female. The age range was from 5
      to 82, the median was 41 years old. In regards 37.7% of patients came from
      Salvador (Bahia, Brazil) and 62.3% from countryside. Valve replacement was
      performed in 73% of patients, whereas 7.38% underwent valvuloplasty and 18.3%
      underwent valve repair and replacement. Regarding type of prosthesis, 70.0%
      received bioprosthesis and 30.0% received metal prosthesis. On note bioprosthesis
      were more used in younger (P<0,001). CONCLUSION: Biological prostheses were used
      predominantly in younger. This might be possible due to a low social-economic
      status, avoiding metal valve implantation and the consequent anticoagulation
      therapy.

PMID- 22996972
TI  - Risk factors for low cardiac output syndrome after coronary artery bypass
      grafting surgery.
AB  - OBJECTIVES: Low cardiac output syndrome (LCOS) is a serious complication after
      cardiac surgery and is associated with significant morbidity and mortality. The
      aim of this study is to identify risk factors for LCOS in patients undergoing
      coronary artery bypass grafting (CABG) in the Division of Cardiovascular Surgery
      of Pronto Socorro Cardiologico de Pernambuco - PROCAPE (Recife, PE, Brazil).
      METHODS: A historical prospective study comprising 605 consecutive patients
      operated between May 2007 and December 2010. We evaluated 12 preoperative and 7
      intraoperative variables. We applied univariate and multivariate logistic
      regression analysis. RESULTS: The incidence of LCOS was 14.7% (n = 89), with a
      lethality rate of 52.8% (n = 47). In multivariate analysis by logistic
      regression, four variables remained as independent risk factors: age > 60 years
      (OR 2.00, 95% CI 1.20 to 6.14, P = 0.009), on-pump CABG (OR 2.16, 95% CI 1.40 to
      7.08, P = 0.006), emergency surgery (OR 4.71, 95% CI 1.34 to 26.55, P = 0.028),
      incomplete revascularization (OR 2.62, 95% CI 1.32 to 5.86, P = 0.003), and
      ejection fraction <50%. CONCLUSIONS: This study identified the following
      independent risk factors for LCOS after CABG: age> 60 years of off-pump CABG,
      emergency surgery, incomplete CABG and ejection fraction <50%.

PMID- 22996973
TI  - Heart defects treatment in Sergipe: propose of resources' rationalization to
      improve care.
AB  - OBJECTIVE: This study aims evaluate the treatment of congenital heart disease
      conducted from 2000 to 2009. METHODS: The sample consisted of all patients
      undergoing surgical correction for congenital heart disease for ten years in
      Sergipe, Brazil. The patients were operated in three hospitals located in the
      city of Aracaju, capital of the state of Sergipe (Brazil). The study was divided
      into two periods defined by the start date of centralization of surgery. The
      variables collected were: age, sex, postoperative diagnosis, destination, type of
      surgery and hospital where the procedure was performed and the classification
      RACHS -1. RESULTS: In the period I, the estimate deficit of surgery was 69%
      decrease occurring in the period II to 55.3%. The postoperative diagnosis was
      more frequent closure of the interventricular communication (20.5%), closure of
      patent ductus arteriosus (20.2%) and atrial septal defect (19%). There was a
      statistically significant correlation between the expected mortality RACHS-1 and
      observed in the sample. The evaluation of RACHS-1 as a predictor of hospital
      mortality by ROC curve showed area of 0.860 95% CI 0.818 to 0.902 with P <0.0001.
      CONCLUSION: The results of this study indicate that the centralization and
      organization of existing resources are needed to improve the performance of
      surgical correction of congenital heart diseases.

PMID- 22996974
TI  - Six-minute walk test as a tool for assessing the quality of life in patients
      undergoing coronary artery bypass grafting surgery.
AB  - OBJECTIVE: To assess the quality of life in patients undergoing myocardial
      revascularization using the six-minute walk test. METHODS: Prospective
      observational study with patients who undergoing CABG. The clinical variables,
      the sixminute walk test, and the SF-36 test were recorded. The patients were
      assessed at the preoperative time and at 2 months of postoperative period.
      According their six-minute walk test results, the patients were divided into two
      groups: group walked more than 350 meters (> 350 meters Group) and the group
      walked less than 350 meters (< 350 meters Group) at the preoperative time.
      RESULTS: Eight-seven patients were included. Age was comparable in both groups
      (59 +/- 9.5 years vs. 61 +/- 9.3 years; respectively, P = 0.24). The group walked
      > 350 meters distance was higher than the < 350 meters group after 2 months of
      operation (436 +/- 78 meters vs. 348 +/- 87 meters; P <0.01). The quality of life
      was lower in the < 350 meters group compared to the > 350 meters group in the
      preoperative period in the following domains: functional capabilities,
      limitations due to physical aspects, overall health feelings, vitality, and
      social aspects. Quality of life improved after two months in both groups.
      CONCLUSIONS: The six-minute walk test at the preoperative time is associated with
      the quality of life after two months of coronary artery bypass grafting. In
      overall, quality of life has improved in all patients. The improvement in the
      quality of life was greater in those patients who walked distances lower than 350
      meters at the preoperative time.

PMID- 22996975
TI  - Predicted preoperative maximal static respiratory pressures in adult cardiac
      surgeries: evaluation of two formulas.
AB  - OBJECTIVES: Cardiac surgery (CC) determines systemic and pulmonary changes that
      require special care. Awareness of the importance of respiratory muscle
      dysfunction in the development of respiratory failure motivated several studies
      conducted in healthy subjects to assess muscle strength. These studies were
      carried out by evaluating the maximal inspiratory pressure (MIP) and maximal
      expiratory pressure (MEP) values. This study examined the concordance among the
      values predicted by the equations proposed by Black & Hyatt and Neder, and the
      measured values in cardiac surgery (CS) patients. METHODS: Data were collected
      from preoperative evaluation forms. The Lin coefficient and Bland-Altman plots
      were used for statistical concordance analysis. The multiple linear regression
      and analysis of variance (ANOVA) were used to produce new formulas. RESULTS:
      There were weak correlations of 0.22 and 0.19 in the MIP analysis and of 0.10 and
      0.32 in the MEP analysis, for the formulas of Black & Hyatt and Neder,
      respectively. The ANOVA for both MIP and MEP were significant (P <0.0001), and
      the following formulas were developed: MIP = 88.82 - (0.51 x age) + (19.86 x
      gender), and MEP = 91.36 - (0.30 x age) + (29.92 x gender). CONCLUSIONS: The
      Black and Hyatt and Neder formulas predict highly discrepant values of MIP and
      MEP and should not be used to identify muscle weakness in CS patients.

PMID- 22996976
TI  - Use of intra-aortic balloon pump in cardiac surgery: analysis of 80 consecutive
      cases.
AB  - BACKGROUND: About 10% to 15% of patients undergoing cardiac surgery may develop
      low cardiac output syndrome in the perioperative period; of this total, 2%
      require mechanical support for adequate hemodynamic control. OBJECTIVE: To
      describe the mortality rates of patients who required the use of IABP in the
      perioperative or postoperative period of cardiac surgery, identifying
      preoperative variables associated with a worse outcome, as well as to describe
      the postoperative complications and medium-term survival. METHODS: Retrospective
      cohort study including 80 consecutive cases between January/2009 and September/
      2011. The patients had on average 62.9 +/- 11.3 years and 58.8% were male; 81.3%
      were hypertensive, 50.0% had prior myocardial infarction and 38.8% has NYHA
      III/IV heart failure. The mainsurgery performed was isolated coronary artery
      bypass grafting (37.5%). RESULTS: Hospital mortality was 53.8% (IC 95%: 42.7
      64.9), and cross-clamp time > 90 minutes was an independent predictor of
      mortality in multivariate analysis (OR 1.52 CI 95%: 1.04-2.22). 71.3% of patients
      (CI 95%: 61.2-81.4) had at least one additional complication in the perioperative
      period, with lower limb ischemia observed in 5.0% patients. One-year survival was
      43.6%, with a plateau in survival rates after a sharp initial drop, related to
      hospital mortality. CONCLUSION: Patients who require IABP comprise a group of
      very high risk for morbidity and mortality. IABP use, however, enables the
      recovery of many patients from an evolution that would invariably be fatal, and
      patients discharged from hospital have a good medium-term survival.

PMID- 22996977
TI  - Calcium dobesilate may improve hemorheology in patients undergoing coronary
      artery bypass grafting.
AB  - BACKGROUND: Calcium dobesilate is an angioprotective agent that has positive
      effects on hemorheological parameters. It is an antioxidant that increases
      endothelial-derived vasodilator substance secretion, there are none that analyze
      its effects during the postoperative period of patients undergoing myocardial
      revascularization. OBJECTIVE: We aimed to determine the effects of calcium
      dobesilate on hemorheological parameters, such as reduced glutathione and
      malondialdehyde in patients with ischemic heart disease undergoing myocardial
      revascularization in the postoperative period. METHODS: One hundred and thirty
      four patients operated for coronary heart disease were included in this study.
      Hemorheological, oxidant and antioxidant parameters were measured two days after
      surgery and after a period of treatment with calcium dobesilate. Then, 500 mg of
      calcium dobesilate was given twice a day to one group of 68 patients for three
      months. The control group was composed of 66 patients who did not receive this
      medication. RESULTS: The increase in the erythrocyte deformability index was
      found to be significant compared with both the pretreatment values and with the
      1st and 2nd values of the control group after calcium dobesilate administration,
      whereas there were no significant changes in blood viscosity, glutathione (GSH)
      or malondialdehyde (MDA) values after the calcium dobesilate administration. The
      same improvement in the CCS class was observed in patients regardless of they
      received the calcium dobesilate treatment. CONCLUSION: In the present
      investigation, the same improvement in the CCS class was observed in patients
      regardless of they received the calcium dobesilate treatment. Improvements with
      calcium dobesilate were statistically significant only in the increase in
      erythrocyte flexibility.

PMID- 22996978
TI  - Results of aortic valve surgery in patients over 75 years old, at 4.5 years of
      follow-up.
AB  - BACKGROUND: The increased longevity elevated the frequency of elderly requiring
      surgery, among them the correction of aortic stenosis. OBJECTIVES: To evaluate
      medium-term mortality, need for reoperation for valve replacement and valve
      complications [systemic thromboembolism (STE) and prosthetic endocarditis (PE)]
      in patients over 75 years old who had undergone surgery for aortic stenosis.
      METHODS: Retrospective study of 230 patients from 2002 to 2007. Mean age was 83.4
      years and 53% were male. The prevalence of hypertension was 73.2%, atrial
      fibrillation 17.9% and previous cardiac surgery 14.4%. Another cardiac procedure
      was associated in 39.1%. RESULTS: In a mean follow-up of 4.51 years the overall
      survival of the population studied was 57.4%. Death in the immediate
      postoperative period occurred in 13.9% (9.4% in the isolated aortic stenosis
      surgery group vs. 20.9% when another procedure was associated). Deaths in the
      medium term occurred in 28.7% of the patients (25.0% vs. 34.4%), with 34 of these
      because of cardiovascular causes. There were 6 cases of PE, 8 cases of STE and 6
      reoperations. The predictors of mortality were ischemia time >90 min (OR 1.99 95%
      CI 1.06-3.74), ejection fraction <60% (OR 1.76 95% CI 1.10-2.81) and prior stroke
      (OR 2.43 95% CI 1.18-5.30). CONCLUSION: Although the immediate surgical risk of
      the elderly is high, survival rates for surgical treatment of patients over 75
      years old are acceptable and allow this intervention. The prognosis is worse
      especially because of the association with coronary artery disease.

PMID- 22996979
TI  - Fetal cardiac output and ejection fraction by spatio-temporal image correlation
      (STIC): comparison between male and female fetuses.
AB  - OBJECTIVE: To compare the cardiac output (CO) and ejection fraction (EF) of the
      heart of male and female fetuses obtained by 3D-ultrasonography using spatio
      temporal image correlation (STIC). METHODS: We conducted a cross-sectional study
      with 216 normal fetuses, between 20 and 34 weeks of gestation, 108 male and 108
      female. Ventricular volumes at the end of systole and diastole were obtained by
      STIC, and the volumetric assessments performed by the virtual organ computer
      aided analysis (VOCAL) rotated 30o. To calculate the DC used the formula: DC =
      stroke volume / fetal heart rate, while for the FE used the formula: EF = stroke
      volume / end-diastolic volume. The DC (combined male and female) and EF (male and
      female) were compared using the unpaired t test and ANCOVA. Scatter plots were
      created with the percentiles 5, 50 and 95. RESULTS: The average of DC combined,
      DC left, DC right, FE right and FE left, male and female were 240.07 mL/min,
      122.67 mL/min, 123.40 mL/min, 72.84%, 67.22%, 270.56 mL/ min, 139.22 mL/min,
      131.34 mL/min, 70.73% and 64.76% respectively, without statistical difference (P>
      0.05). CONCLUSIONS: The fetal CO and EF obtained by 3Dultrasonography (STIC)
      showed no significant difference in relation to gender.

PMID- 22996980
TI  - Flowmetry of left internal thoracic artery graft to left anterior descending
      artery: comparison between on-pump and off-pump surgery.
AB  - BACKGROUND: Off-pump coronary bypass grafting (OPCAB) has become a widely used
      technique. Coronary flowmetry is the most common method employed to assess graft
      patency, nevertheless, few studies compare flow patterns between ONCAB and OPCAB
      surgery. The objective of this study was to compare flowmetry data in left
      internal mammary artery grafts bypasses to the left anterior descendent artery.
      METHODS: From March to September of 2010, thirtyfive consecutive, non-randomized
      patients underwent CABG and were retrospectively evaluated. Ten patients were
      located on group A (On Pump), and twenty-five on group B (Off Pump). The mean
      graft flow (MGF), pulsatile index (PI) and diastolic filling (DF) were obtained
      using Transit Time Flowmetry (TTFM). The Fisher exact test, and Mann Whitney test
      were used, and a P value of < 0.05 was considered to indicate statistical
      significance. RESULTS: There were no deaths, AMI, re-interventions or PTCA in a
      30-day period. The number of bypasses performed per patient was 2.3 +/- 0.8 in
      the OPCAB group, and 2.2 +/- 0.6 in the ONCAB group, with no significant
      difference (P=0.10). The median of mean flow was 23 ml/min on group A, and 25
      ml/min on group B (P=0.34). Diastolic filling percentage was 56% on group A, and
      56.9% on group B (P=0.86). Pulsatile Index was 2.3 on group A, and 2.2 on group B
      (P=0.82). CONCLUSIONS: There was no difference between TTFM values (MF, PI and
      DF) in patients operated with or without cardiopulmonary bypass.

PMID- 22996981
TI  - Initial experience with Pomerantzeff's technique for reduction of the size of
      giant left atrium.
AB  - INTRODUCTION: The most common indication for surgical correction of giant left
      atrium is associated with mitral valve insufficiency with or without atrial
      fibrillation. Several techniques for this purpose are already described with
      varying results. OBJECTIVE: To present the initial experience with the tangential
      triangular resection technique (Pomerantzeff). METHODS: From 2002 to 2010, four
      patients underwent mitral valve operation with reduction of left atrial volume by
      the technique of triangular resection tangential in our service. Three patients
      were female. The age ranged from 21 to 51 years old. The four patients presented
      with atrial fibrillation. Ejection fraction of left ventricle preoperatively
      ranged from 38% to 62%. The left atrial diameter ranged from 78mm to 140mm. After
      treatment of mitral dysfunction, the left atrium was reduced by resecting
      triangular tangential posterior wall between the pulmonary veins to avoid
      anatomic distortion of the mitral valve or pulmonary veins, reducing tension in
      the suture line. RESULTS: Average hospital stay was 21.5 +/- 6.5 days. The mean
      cardiopulmonary bypass time was 130 +/- 30 minutes. There was no surgical
      bleeding or mortality in the postoperative period. All patients had sinus rhythm
      restored in the output of cardiopulmonary bypass, maintaining this rate
      postoperatively. The average diameter of the left atrium was reduced by 50.5% +/-
      19.5%. The left ventricular ejection fraction improved in all patients.
      CONCLUSION: Initial results with this technique have shown effective reduction of
      the left atrium.

PMID- 22996982
TI  - Point-of-care test (POCT) INR: hope or illusion?
AB  - In the last decade, point-of-care tests were developed to provide rapid
      generation of test results. These tests have increasingly broad applications. In
      the area of hemostasis, the international normalized ratio, INR point-of-care
      test (POCT INR), is the main test of this new proposal. This test has great
      potential benefit in situations where the quick INR results influences clinical
      decision making, as in acute ischemic stroke, before surgical procedures and
      during cardiac surgery. The INR POCT has the potential to be used for self
      monitoring of oral anticoagulation in patients under anticoagulant therapy.
      However, the precision and accuracy of INR POCT still need to be enhanced to
      increase effectiveness and efficiency of the test. Additionally, the RDC / ANVISA
      Number 302 makes clear that the POCT testing must be supervised by the technical
      manager of the Clinical Laboratory in the pre-analytical, analytical and post
      analytical. In practice, the Clinical Laboratory does not participate in the
      implementation of POCT testing or release of the results. Clinicians have high
      expectation with the incorporation of INR POCT in clinical practice, despite the
      limitations of this method. These professionals are willing to train the patient
      to perform the test, but are not legally responsible for the quality of it and
      are not prepared for the maintenance of equipment. The definition of who is in
      charge for the test must be one to ensure the quality control.

PMID- 22996983
TI  - Cardiology in Brazilian scientific journals: an overview.
AB  - Cardiology has been and is a very significant fraction of the Brazilian
      contribution to science. In older days, the most significant part of this work
      was directed to foreign periodicals, but the quasi-simultaneous emergence of
      SciELO and PUBMED has ordained a redirection of much of this work to Brazilian
      periodicals. We here survey some of this more recent contribution for the benefit
      of readers of Revista Brasileira de Cirurgia Cardiovascular. This is offered as
      an update. Articles on the general themes of Cardiology and Pneumology published
      by four ISI Indexed Brazilian journals not specializing in cardiology are re
      visited, after a search through 10 journals.

PMID- 22996984
TI  - Conservative surgical management of mitral insufficiency: an alternative
      approach.
AB  - Mitral valve insufficiency is frequently the result of elongated or ruptured
      chordae tendineae. Several techniques have been described for its correction.
      However, when there is a severe elongation or rupture of the chordae, the most
      widely accepted treatment option has been valve replacement. The best long-term
      outcomes observed in conservative surgeries led us to choose this procedure
      rather than the correction of mitral valve insufficiency. We described three
      techniques for correction of mitral prolapse due to elongated and/or ruptured
      chordae tendineae. In addition, we developed mold pre built bovine pericardial
      chords (Braile-Gregori prosthesis) for chordae replacement. Finally, since 1987,
      the rigid prosthetic semicircular ring (Gregori-Braile ring) has been
      consistently used in our centre for correction of the posterior dilation of
      mitral annulus preferably in its portion close to the posteromedial commissure.

PMID- 22996985
TI  - Greek language: analysis of the cardiologic anatomical etymology: past and
      present.
AB  - INTRODUCTION: The Greek language, the root of most Latin anatomical terms, is
      deeply present in the Anatomical Terminology. Many studies seek to analyze
      etymologically the terms stemming from the Greek words. In most of these studies,
      the terms appear defined according to the etymological understanding of the
      respective authors at the time of its creation. Therefore, it is possible that
      the terms currently used are not consistent with its origin in ancient Greek
      words. METHODS: We selected cardiologic anatomical terms derived from Greek
      words, which are included in the International Anatomical Terminology. We
      performed an etymological analysis using the Greek roots present in the earliest
      terms. We compared the cardiologic anatomical terms currently used in Greece and
      Brazil to the Greek roots originating from the ancient Greek language. We used
      morphological decomposition of Greek roots, prefixes, and suffixes. We also
      verified their use on the same lexicons and texts from the ancient Greek
      language. RESULTS: We provided a list comprising 30 cardiologic anatomical terms
      that have their origins in ancient Greek as well as their component parts in the
      International Anatomical Terminology. We included the terms in the way they were
      standardized in Portuguese, English, and Modern Greek as well as the roots of the
      ancient Greek words that originated them. CONCLUSION: Many works deal with the
      true origin of words (etymology) but most of them neither returns to the earliest
      roots nor relate them to their use in texts of ancient Greek language. By
      comparing the world's greatest studies on the etymology of Greek words, this
      paper tries to clarify the differences between the true origin of the Greek
      anatomical terms as well as the origins of the cardiologic anatomical terms more
      accepted today in Brazil by health professionals.

PMID- 22996986
TI  - Heart retransplantation in children without the use of blood product.
AB  - This article reports a case of a cardiac retransplantation without the use of
      blood products, in a 6 year old, with severe dilated cardiomyopathy after chronic
      graft rejection and refractory to clinical treatment. To avoid a blood
      transfusion in this surgery a multidisciplinary approach was planned, which
      involved the use of preoperative erythropoietin, acute normovolemic hemodilution
      and intraoperative cell savage with autologous blood recovery system, as well as
      a meticulous hemostasis and reduced postoperative phlebotomy.

PMID- 22996987
TI  - The medical education and the Unified Health System.

PMID- 22996988
TI  - Evidence-based medicine - new paradigm or pseudoscience?

PMID- 22996991
TI  - Pediatric cardiovascular surgery: what we must preserve, what we should improve
      and what we must transform.

PMID- 22996992
TI  - On- and off-pump coronary artery bypass surgery. The heart surgeon should master
      both techniques.

PMID- 22996993
TI  - The risk of risk scores and the dream of BraSCORE.

PMID- 22996994
TI  - Multiple stressor effects of predation by rotifers and herbicide pollution on
      different Chlamydomonas strains and potential impacts on population dynamics.
AB  - Environmental factors can interact with the effects of chemical pollutants on
      natural systems by inducing multiple stressor effects in individual organisms as
      well as by altering selection pressure on tolerant strains in heterogeneous
      populations. Predation is a stressful environmental factor relevant for many
      species. Therefore, the impact of predation by the rotifer Brachionus
      calyciflorus on tolerance of eight genetically different strains of the green
      alga Chlamydomonas reinhardtii to simultaneous exposure to each of the three
      herbicides (diuron, paraquat, and S-metolachlor) was tested. Interactions of
      combined stressors were analyzed based on the independent action model; additive,
      synergistic, and antagonistic effects of the combined exposure could be detected
      depending on the herbicide and strain tested. If cultures were acclimated (pre
      exposed) to one stressor, tolerance to the second stressor could be increased.
      This indicates that physiological changes can induce cotolerance of predation
      exposed algae to herbicides and of herbicide-treated algae to predation depending
      on the combination of stressors. The strain-specific differences in multiple
      stressor effects also changed the correlation of strains' tolerances to
      individual stressors determined during combined and single-stressor exposure.
      Changes in cotolerance to stressors affect selection pressure and population
      dynamics during long-term exposure. This shows that predation stress can have
      adverse effects on the toxicity of chemical pollutants to microalgae on the
      organism and population levels.

PMID- 22996995
TI  - Functional mapping of human sound and carious enamel and dentin with Raman
      spectroscopy.
AB  - The goals of this trial were, first, to produce a Raman mapping of decay and
      sound dentin samples, through accurate analysis of the Raman band spectra
      variations of mineral and organic components. The second goal was to confirm the
      correlation between the Raman signal and the signal of a fluorescent camera, by
      assaying the concentration of pentosidine and natural collagen fluorescent
      crosslink using reverse phase high-pressure liquid chromatography. The first
      correlation assumed a possible relationship between the signal observed with the
      camera and Raman spectroscopy. The second correlation assumed an association with
      the Maillard reaction. Absence of a correlation for this trial was that no
      association could be found between Raman spectra characteristics, fluorescence
      variation and the HPLC assay. Our results void this absence.

PMID- 22996996
TI  - Zoledronic acid but not somatostatin analogs exerts anti-tumor effects in a model
      of murine prostatic neuroendocrine carcinoma of the development of castration
      resistant prostate cancer.
AB  - BACKGROUND: Since neuroendocrine (NE) cells play an important role in the
      development of castration-resistant prostate cancer (CRPC), target therapy to NE
      cells should be considered for treating CRPC. We investigated the effects
      zoledronic acid (ZOL) and two somatostatin analogs (octreotide: SMS, and
      pasireotide: SOM) on an NE allograft (NE-10) and its cell line (NE-CS), which
      were established from the prostate of the LPB-Tag 12T-10 transgenic mouse.
      METHODS: We examined the in vivo effects of ZOL, SMS and SOM as single agents and
      their combinations on subcutaneously inoculated NE-10 allografts and the in vitro
      effects on NE-CS cells. Apoptosis and cell cycle activity were assessed by
      immunohistochemistry using TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and
      a Ki-67 antibody, respectively. RESULTS: In vivo growth of NE-10 tumors treated
      with ZOL, ZOL plus SMS, or ZOL plus SOM was significantly inhibited compared to
      the control as a consequence of induction of apoptosis and cell cycle arrest. ZOL
      induced time- and dose-dependent inhibition of in vitro proliferation of NE-CS
      cells, but the somatostatin analogs (SMS and SOM) did not. ZOL also inhibited
      migration of NE-CS cells. These effects were caused by inhibition of Erk1/2
      phosphorylation via impairment of prenylation of Ras. CONCLUSIONS: ZOL, but not
      SMS or SOM, induced apoptosis and inhibition of proliferation and migration
      through impaired prenylation of Ras in NE carcinoma models. Our findings support
      the possibility that ZOL could be used in the early phase for controlling NE
      cells, which may trigger progression to CRPC.

PMID- 22996997
TI  - OSHA does not kill jobs; it helps prevent jobs from killing workers.

PMID- 22996998
TI  - Synthesis, structure, tautomerism, and reactivity of methanetrisamidines.

PMID- 22996999
TI  - A study of interactions between bacteria and antibiotics by capillary
      electrophoresis.
AB  - To assess the bacteria-antibiotic interactions in patients with postoperative
      wound infections, a simple electrophoretic test was performed. To estimate the
      effectiveness of the antibiotic therapy and to prepare 3-day profiles of bacteria
      "quantity" in biological samples, CE was used. As our team demonstrated earlier,
      the method is easy and fast, sample pretreatment is not necessary, and it is
      characterized by high selectivity. Finally, the statistically optimal and
      significant results of the CZE test analysis for detection of Escherichia coli
      cells was established for migration time lower than 3.5 min. The obtained
      sensitivity and specificity amounted to 89.5 and 100%, respectively. It is the
      first application of CZE in the study of medical therapy.

PMID- 22997000
TI  - Radical localization in a series of symmetric Ni(II) complexes with oxidized
      salen ligands.
AB  - Square-planar nickel(II) complexes of salen ligands, N,N'-bis(3-tert-butyl-(5R)
      salicylidene)-1,2-cyclohexanediamine), in which R=tert-butyl (1), OMe (2), and
      NMe(2) (3), were prepared and the electronic structure of the one-electron
      oxidized species [1-3](+.) was investigated in solution. Cyclic voltammograms of
      [1-3] showed two quasi-reversible redox waves that were assigned to the oxidation
      of the phenolate moieties to phenoxyl radicals. From the difference between the
      first and second redox potentials, the trend of electronic delocalization 1(+.)
      >2(+.) >3(+.) was obtained. The cations [1-3](+.) exhibited isotropic g tensors
      of 2.045, 2.023, and 2.005, respectively, reflecting a lower metal character of
      the singly occupied molecular orbital (SOMO) for systems that involve strongly
      electron-donating substituents. Pulsed-EPR spectroscopy showed a single
      population of equivalent imino nitrogen atoms for 1(+.), whereas two distinct
      populations were observed for 2(+.). The resonance Raman spectra of 2(+.) and
      3(+.) displayed the nu(8a) band of the phenoxyl radicals at 1612 cm(-1), as well
      as the nu(8a) bands of the phenolates. In contrast, the Raman spectrum of 1(+.)
      exhibited the nu(8a) band at 1602 cm(-1), without any evidence of the phenolate
      peak. Previous work showed an intense near-infrared (NIR) electronic transition
      for 1(+.) (Deltanu(1/2) =660 cm(-1), epsilon=21,700 M(-1) cm(-1)), indicating
      that the electron hole is fully delocalized over the ligand. The broader and
      moderately intense NIR transition of 2(+.) (Deltanu(1/2) =1250 cm(-1) ,
      epsilon=12,800 M(-1) cm(-1)) suggests a certain degree of ligand-radical
      localization, whereas the very broad NIR transition of 3(+.) (Deltanu(1/2) =8630
      cm(-1), epsilon=2550 M(-1) cm(-1)) indicates significant localization of the
      ligand radical on a single ring. Therefore, 1(+.) is a Class III mixed-valence
      complex, 2(+.) is Class II/III borderline complex, and 3(+.) is a Class II
      complex according to the Robin-Day classification method. By employing the
      Coulomb-attenuated method (CAM-B3LYP) we were able to predict the electron-hole
      localization and NIR transitions in the series, and show that the energy match
      between the redox-active ligand and the metal d orbitals is crucial for
      delocalization of the radical SOMO.

PMID- 22997001
TI  - A real-time internal dose assessment exercise.
AB  - A real-time internal dose assessment exercise has been conducted in which
      participants were required to make decisions about sampling requirements, seek
      relevant information about the 'incident' and make various interim dose
      assessments. At the end of the exercise, each participant was requested to make a
      formal assessment, providing statements of the methods, models and assumptions
      used in that assessment. In this paper we describe how the hypothetical
      assessment case was set up and the exercise was conducted, the responses of the
      participants and the assessments of dose that they made. Finally we discuss the
      lessons learnt from the exercise and suggest how the exercise may be adapted to a
      wider range of participants.

PMID- 22997002
TI  - Transforming primary care training--patient-centered medical home entrustable
      professional activities for internal medicine residents.
AB  - INTRODUCTION: The U.S. faces a critical gap between residency training and
      clinical practice that affects the recruitment and preparation of internal
      medicine residents for primary care careers. The patient-centered medical home
      (PCMH) represents a new clinical microsystem that is being widely promoted and
      implemented to improve access, quality, and sustainability in primary care
      practice. AIM: We address two key questions regarding the training of internal
      medicine residents for practice in PCMHs. First, what are the educational
      implications of practice transformations to primary care home models? Second,
      what must we do differently to prepare internal medicine residents for their
      futures in PCMHs? PROGRAM DESCRIPTION: The 2011 Society of General Internal
      Medicine (SGIM) PCMH Education Summit established seven work groups to address
      the following topics: resident workplace competencies, teamwork, continuity of
      care, assessment, faculty development, 'medical home builder' tools, and policy.
      The output from the competency work group was foundational for the work of other
      groups. The work group considered several educational frameworks, including
      developmental milestones, competencies, and entrustable professional activities
      (EPAs). RESULTS: The competency work group defined 25 internal medicine resident
      PCMH EPAs. The 2011 National Committee for Quality Assurance (NCQA) PCMH
      standards served as an organizing framework for EPAs. DISCUSSION: The list of
      PCMH EPAs has the potential to begin to transform the education of internal
      medicine residents for practice and leadership in the PCMH. It will guide
      curriculum development, learner assessment, and clinical practice redesign for
      academic health centers.

PMID- 22997003
TI  - Prenatal diagnosis of 22q11.2 deletion syndrome in twin pregnancy: a case report.
AB  - Chromosome 22q11.2 deletion syndrome is a common genetic disorder, also known as
      DiGeorge syndrome. It occurs in approximately 1:4,000 births, and the incidence
      is increasing due to affected parents bearing their own affected children. We
      report the prenatal diagnosis of 22q11.2 deletion syndrome by fluorescence in
      situ hybridization in twin fetuses having tetralogy of Fallot with absent
      pulmonary valve.

PMID- 22997004
TI  - Transcatheter aortic valve implantation for severe regurgitation in native and
      degenerated bioprosthetic aortic valves.
AB  - OBJECTIVES: We evaluated transcatheter aortic valve Implantation (TAVI) in high
      risk patients with severe aortic regurgitation (AR) in native or degenerated
      bioprosthetic valves. BACKGROUND: TAVI has emerged as a viable treatment modality
      for severe aortic stenosis in inoperable or high-risk patients. The use of TAVI
      for treatment of severe AR has remained largely unexplored. METHODS: Eight
      patients (age 79.6 years +/- 5.75 years) with severe AR underwent TAVI at six
      tertiary hospitals between April 2010 and May 2011. All patients were considered
      to be at prohibitive risk for surgical aortic valve replacement (SAVR).TAVI with
      the nitinol based Core Valve bioprosthesis (CRS) (Medtronic) was performed in all
      patients. RESULTS: Transfemoral access was used in all cases. Procedural success
      was obtained in all cases without any intraprocedural complications. There was no
      in hospital or 30-day mortality. There were no cases of atrioventricular blocks
      requiring permanent pacemaker implantation. At a mean follow up of 15.5 +/- 15
      months; all patients had improvement in New York Heart Association functional
      class. Follow up echocardiography revealed improved or stable left ventricular
      ejection fraction and optimal device function in all cases. CONCLUSIONS: TAVI
      with the CRS bioprosthesis is feasible and effective in appropriately selected
      cases of severe aortic regurgitation in native and bioprosthetic aortic valves.

PMID- 22997005
TI  - Supramolecular approach by using Jahn-Teller sites to construct a {Mn13}-based
      coordination polymer and modify its magnetic properties.
AB  - Put a spin on it: a {Mn(13)} coordination cluster has been used as a secondary
      building unit for the preparation of an open-framework structure for which the
      magnetic properties can be modified by solution adsorption of
      tetracyanoquinodimethane radical anions (TCNQ.(-)). The applied supramolecular
      approach takes advantage of kinetically labile Jahn-Teller sites and can be
      generalised for the construction and post-synthetic modification of
      multifunctional materials.

PMID- 22997006
TI  - Concise review: Spermatogenesis in an artificial three-dimensional system.
AB  - Culture of spermatogonial stem cells has been performed under a variety of
      conditions. Most featured two-dimensional systems, with different types of sera,
      conditioned media, feeder layers, and growth factors. Some have used three
      dimensional (3D) matrices produced from gelatin, collagen, or other material. In
      spite of their increasingly sophisticated composition, however, complete
      spermatogenesis in vitro has not yet been achieved. In the seminiferous tubules,
      spermatogenesis occurs in an environment where cells are embedded in a 3D
      structure with specific niches regulating each stage of germ cell maturation
      mediated by hormones and paracrine/autocrine factors. We have recently reported
      achievement of complete in vitro spermatogenesis of mouse testicular germ cells
      in a 3D culture system featuring a soft agar matrix. This review discusses the
      advantages of the 3D culture system for studying the spermatogenic process in its
      entirety. Also discussed are the steps necessary to expand the applicability of
      the 3D culture system to human germ cell development and determine the
      functionality of culture-produced spermatozoa for generating offspring.

PMID- 22997007
TI  - Pitch-tunable size reduction patterning with a temperature-memory polymer.
AB  - A scalable and pitch-tunable size reduction patterning method is introduced by
      exploiting the temperature memory effect of shape memory polymer and replica
      molding of UV-curable materials.

PMID- 22997009
TI  - Beyond surface markers with a universal cell secretion assay.

PMID- 22997010
TI  - Optimization of sample preparation conditions for detecting trace amounts of beta
      tegafur in alpha- and beta-tegafur mixture.
AB  - We report a semiquantitative method for determining trace amounts (<1%) of
      thermodynamically stable forms in polymorphic mixtures, focusing on sample
      preparation effects on solid phase transitions. Tegafur [5-fluoro-1-(oxolan-2-yl)
      1,2,3,4-tetrahydropyrimidine-2,4-dione] was used as a model material in this
      study. The amounts of the thermodynamically stable beta tegafur were increased to
      levels detectable by powder X-ray diffractometry by grinding the samples in a
      ball mill in the presence of water. The limit of detection for this method was as
      low as 0.0005% of beta tegafur in alpha and beta tegafur mixtures. The amount of
      beta tegafur after sample preparation was found to be proportional to the initial
      weight fraction of beta tegafur. The sum of Langmuir and Cauchy-Lorentz equations
      was used to describe the change in conversion degree due to the added water
      volume, where Langmuir equation described water sorption during the sample
      preparation and Cauchy-Lorentz equation described the grinding efficiency.

PMID- 22997008
TI  - Carbon source-induced reprogramming of the cell wall proteome and secretome
      modulates the adherence and drug resistance of the fungal pathogen Candida
      albicans.
AB  - The major fungal pathogen Candida albicans can occupy diverse microenvironments
      in its human host. During colonization of the gastrointestinal or urogenital
      tracts, mucosal surfaces, bloodstream, and internal organs, C. albicans thrives
      in niches that differ with respect to available nutrients and local environmental
      stresses. Although most studies are performed on glucose-grown cells, changes in
      carbon source dramatically affect cell wall architecture, stress responses, and
      drug resistance. We show that growth on the physiologically relevant carboxylic
      acid, lactate, has a significant impact on the C. albicans cell wall proteome and
      secretome. The regulation of cell wall structural proteins (e.g. Cht1, Phr1,
      Phr2, Pir1) correlated with extensive cell wall remodeling in lactate-grown cells
      and with their increased resistance to stresses and antifungal drugs, compared
      with glucose-grown cells. Moreover, changes in other proteins (e.g. Als2, Gca1,
      Phr1, Sap9) correlated with the increased adherence and biofilm formation of
      lactate-grown cells. We identified mating and pheromone-regulated proteins that
      were exclusive to lactate-grown cells (e.g. Op4, Pga31, Pry1, Scw4, Yps7) as well
      as mucosa-specific and other niche-specific factors such as Lip4, Pga4, Plb5, and
      Sap7. The analysis of the corresponding null mutants confirmed that many of these
      proteins contribute to C. albicans adherence, stress, and antifungal drug
      resistance. Therefore, the cell wall proteome and secretome display considerable
      plasticity in response to carbon source. This plasticity influences important
      fitness and virulence attributes known to modulate the behavior of C. albicans in
      different host microenvironments during infection.

PMID- 22997011
TI  - Quantification of DNA in simple eukaryotic cells using Fourier transform infrared
      spectroscopy.
AB  - A technique capable of detecting and monitoring nucleic acid concentration offers
      potential in diagnosing cancer and further developing an understanding of the
      biochemistry of disease. The application of Fourier transform infrared (FTIR)
      spectroscopy has previously been hindered by the supposed non-Beer-Lambert
      absorption behavior of DNA in intact cells making elucidation of the DNA bands
      difficult. We use known composition DNA/hemoglobin standards to successfully
      estimate the DNA content in avian erythrocyte nuclei (44.2%) and intact
      erythrocytes (12.8%). Furthermore we demonstrate that the absorption of cellular
      DNA does follow the Beer-Lambert Law and highlights the role of conformation and
      hydration in FTIR spectroscopy of biological samples.

PMID- 22997012
TI  - Anion responsive imidazolium-based polymers.
AB  - Stimuli responsiveness in polymer design is providing basis for diversely new and
      advanced materials that exhibit switchable porosity in membranes and coatings,
      switchable particle formation and thermodynamically stable nanoparticle
      dispersions, polymers that provide directed mechanical stress in response to
      intensive fields, and switchable compatibility of nanomaterials in changing
      environments. The incorporation of ionic liquid monomers has resulted in many new
      polymers based on the imidazolium group. These polymers exhibit all of the above
      articulated material properties. Some insight into how these anion responsive
      polymers function has become empirically available. Much opportunity remains for
      extending our understanding as well as for designing more refined stimuli
      responsive materials.

PMID- 22997013
TI  - Effect of chronic exposure to zinc in young spats of the Pacific oyster
      (Crassostrea gigas).
AB  - The marine coastal environment is exposed to a mixture of environmental
      pollutants of anthropogenic origin, resulting in chronic low concentrations of
      contaminants. As a consequence, most coastal marine species are exposed to low
      doses of such pollutants during their entire life. Many marine species live for
      years in their natural environment, whereas they do not under laboratory exposure
      conditions. Using early stages of development in laboratory work allows animals
      to be chronically exposed from an early age over a reasonable experiment period.
      In the present study, the authors investigated the effect of chronic exposure to
      zinc in spats of the Pacific oyster (Crassostrea gigas), from metamorphosis up to
      10 weeks. The authors investigated integrated biological endpoints that would
      account for the apparent general health of the animals as well as molecular
      markers showing more subtle effects that could potentially go unnoticed at a
      biologically integrated level. The authors measured in parallel both growth and
      the transcriptional level of target stress genes. Growth was monitored by image
      analysis of large samples to avoid high variability and ensure statistical
      robustness. A dose-response relationship was derived from growth data, yielding a
      median effective concentration (EC50) of 7.55 uM. Stress genes selected on the
      basis of available RNA sequences in C. gigas included genes involved in chaperone
      proteins, oxidative stress, detoxification, and cell cycle regulation. Out of
      nine stress target genes, only metallothionein displayed overexpression in
      response to high levels of zinc.

PMID- 22997014
TI  - Anatomy of the human mammary gland: Current status of knowledge.
AB  - Mammary glands are unique to mammals, with the specific function of synthesizing,
      secreting, and delivering milk to the newborn. Given this function, it is only
      during a pregnancy/lactation cycle that the gland reaches a mature developmental
      state via hormonal influences at the cellular level that effect drastic
      modifications in the micro- and macro-anatomy of the gland, resulting in
      remodeling of the gland into a milk-secretory organ. Pubertal and post-pubertal
      development of the breast in females aids in preparing it to assume a functional
      state during pregnancy and lactation. Remarkably, this organ has the capacity to
      regress to a resting state upon cessation of lactation, and then undergo the same
      cycle of expansion and regression again in subsequent pregnancies during
      reproductive life. This plasticity suggests tight hormonal regulation, which is
      paramount for the normal function of the gland. This review presents the current
      status of knowledge of the normal macro- and micro-anatomy of the human mammary
      gland and the distinct changes it undergoes during the key developmental stages
      that characterize it, from embryonic life through to post-menopausal age. In
      addition, it discusses recent advances in our understanding of the normal
      function of the breast during lactation, with special reference to breastmilk,
      its composition, and how it can be utilized as a tool to advance knowledge on
      normal and aberrant breast development and function. Finally, anatomical and
      molecular traits associated with aberrant expansion of the breast are discussed
      to set the basis for future comparisons that may illuminate the origin of breast
      cancer.

PMID- 22997016
TI  - Sterically-limited self-assembly of Pt4 macrocycles into discrete non-covalent
      nanotubes: porous supramolecular tetramers and hexamers.
AB  - We report a template-free strategy based on steric repulsion for the isolation of
      discrete columnar aggregates of macrocycles. Specifically, introduction of
      sterically-demanding trityl-derived substituents at the periphery of Pt(4) Schiff
      base macrocycles limits the otherwise infinite one-dimensional columnar
      aggregation to discrete tetrameric and hexameric assemblies. Single crystal X-ray
      diffraction studies of these compounds reveal discrete nanotubes of finite length
      that pack inefficiently resulting in three-dimensional networks of interconnected
      void space. The discrete assemblies were studied by N(2) adsorption and show
      enhanced surface area when stacked. In the absence of bulky substituents the
      macrocycles are nonporous. This strategy for engineering discrete supramolecular
      macrocyclic aggregates may be generalized to other columnar assembling systems.

PMID- 22997017
TI  - Advances in childhood cancers: whole-genome sequencing has helped identify cancer
      subtypes and potential targets for therapy.

PMID- 22997018
TI  - Drug helps slow advanced prostate cancer.

PMID- 22997015
TI  - Genetically encoded cyclopropene directs rapid, photoclick-chemistry-mediated
      protein labeling in mammalian cells.
AB  - We just click: Genetic incorporation of a cyclopropene amino acid CpK (see
      scheme) site-specifically into proteins in E. coli and mammalian cells was
      achieved using an orthogonal aminoacyl-tRNA synthetase/tRNA(CUA) pair
      (CpKRS/MbtRNA(CUA)). Cyclopropene exhibited fast reaction kinetics in the
      photoclick reaction and allowed rapid (ca. 2 min) labeling of proteins.

PMID- 22997019
TI  - Expert says breast cancer risk can be lowered by reducing unnecessary imaging.

PMID- 22997020
TI  - Sonographic hepatorenal ratio: a noninvasive method to diagnose nonalcoholic
      steatosis.
AB  - PURPOSE: To evaluate the accuracy of the sonographic hepatorenal ratio (HRR) in
      the diagnosis and grading of nonalcoholic steatosis, using biopsy as the
      reference. METHODS: Ultrasound (US) and liver biopsy were performed in 42
      patients with nonalcoholic fatty liver disease. Forty healthy volunteers without
      steatosis at US and without risk factors for nonalcoholic fatty liver disease
      were also studied. The HRR was obtained by dividing the mean brightness level of
      region-of-interest pixels in hepatic parenchyma by that in renal parenchyma.
      Needle biopsy samples (hematoxylin-eosin stained) were classified as mild (5-33%
      fatty infiltration), moderate (>33-66%), or severe (>66%) steatosis. Spearman
      coefficient was used to evaluate the correlation between HRR and steatosis grade,
      analysis of variance for differences between subgroups, and receiver operating
      characteristic curve analysis for sensitivity and specificity. RESULTS:
      Significant correlation was found between HRR and histologic steatosis (r = 0.80,
      p < 0.01). The HRR cutoff for predicting steatosis was >=1.24 (sensitivity,
      92.7%; specificity, 92.5%). The mean +/- SD HRRs in controls and steatosis
      subgroups were control 1.09 +/- 0.13, mild 1.46 +/- 0.24, moderate 1.52 +/- 0.27,
      severe 2.04 +/- 0.3 and were significantly different from each other except
      between mild and moderate steatosis subgroups. CONCLUSIONS: The HRR is a
      noninvasive, objective, and simple method that could be used to diagnose and
      grade hepatic steatosis.

PMID- 22997021
TI  - Determination of neonicotinoid insecticides in environmental samples by micellar
      electrokinetic chromatography using solid-phase treatments.
AB  - A sensitive and reliable method based on MEKC has been developed and validated
      for trace determination of neonicotinoid insecticides (thiamethoxam, acetamiprid,
      and imidacloprid) and the metabolite 6-chloronicotinic acid in water and soil
      matrices. Optimum separation of the neonicotinoid insecticides was obtained on a
      58 cm long capillary (75 MUm id) using as the running electrolyte 40 mM SDS, 5 mM
      borate (pH 10.4), and 5% (v/v) methanol at a temperature of 25 degrees C, a
      voltage of 25 kV and with hydrodynamic injection (10 s). The analysis time was
      less than 7 min. Prior to MEKC determination, the samples were purified and
      enriched by carrying out extraction-preconcentration steps. For aqueous samples,
      off-line SPE with a sorptive material such as Strata-X (polymeric hydrophobic
      sorbent) and octadecylsilane (C18) was carried out to clean up and preconcentrate
      the insecticides. However, for soil samples, matrix solid-phase dispersion (MSPD)
      was applied with C18 used as the dispersant. Good linearity, accuracy, and
      precision were obtained and the detection limits were in the range between 0.01
      and 0.07 MUg mL-1 for river water and 0.17 and 0.37 MUg g-1 for soil samples.
      Recovery levels reached greater than 92% for all of the assayed neonicotinoids in
      river water samples with Strata-X. In soil matrices, the best recoveries (63-99%)
      were obtained with MSPD.

PMID- 22997022
TI  - Solution of the Generalized Noah's Ark Problem.
AB  - The phylogenetic diversity (PD) of a set of species is a measure of the
      evolutionary distance among the species in the collection, based on a
      phylogenetic tree. Such a tree is composed of a root, internal nodes, and leaves
      that correspond to the set of taxa under study. With each edge of the tree is
      associated a non-negative branch length (evolutionary distance). If a particular
      survival probability is associated with each taxon, the PD measure becomes the
      expected PD measure. In the Noah's Ark Problem (NAP) introduced by Weitzman
      (1998), these survival probabilities can be increased at some cost. The problem
      is to determine how best to allocate a limited amount of resources to maximize
      the expected PD of the considered species. It is easy to formulate the NAP as a
      (difficult) nonlinear 0-1 programming problem. The aim of this article is to show
      that a general version of the NAP (GNAP) can be solved simply and efficiently
      with any set of edge weights and any set of survival probabilities by using
      standard mixed-integer linear programming software. The crucial point to move
      from a nonlinear program in binary variables to a mixed-integer linear program,
      is to approximate the logarithmic function by the lower envelope of a set of
      tangents to the curve. Solving the obtained mixed-integer linear program provides
      not only a near-optimal solution but also an upper bound on the value of the
      optimal solution. We also applied this approach to a generalization of the nature
      reserve problem (GNRP) that consists of selecting a set of regions to be
      conserved so that the expected PD of the set of species present in these regions
      is maximized. In this case, the survival probabilities of different taxa are not
      independent of each other. Computational results are presented to illustrate
      potentialities of the approach. Near-optimal solutions with hypothetical
      phylogenetic trees comprising about 4000 taxa are obtained in a few seconds or
      minutes of computing time for the GNAP, and in about 30 min for the GNRP. In all
      the cases the average guarantee varies from 0% to 1.20%.

PMID- 22997023
TI  - Quantifying the effect of nanoparticles on As(V) ecotoxicity exemplified by nano
      Fe2 O3 (magnetic) and nano-Al2 O3.
AB  - Nano-Fe(2) O(3) (magnetic) and nano-Al(2) O(3) are increasingly used in
      biomedical fields for cellular labeling and drug delivery, and in the industry as
      catalysts. However, they may also serve as carriers of toxic contaminants and
      negatively impact the environment and human health. In the present study,
      Ceriodaphnia dubia was used to assess the toxicity of these nanoparticles (NPs)
      with and without the presence of background arsenic(V) (As[V]). The results
      showed that although these NPs alone did not exhibit significant toxicity in the
      experimental concentration range, they could significantly enhance the toxicity
      of As(V). The accumulation of As(V) on nano-Fe(2) O(3) (m) and nano-Al(2) O(3) ,
      as well as the uptake of these NPs in C. dubia, were verified. An inverse
      relationship between the median lethal concentration (LC50) of the soluble As(V)
      and the accumulation of NPs in C. dubia was developed. Therefore, the uptake of
      As(V)-loaded NPs in C. dubia played a key role in enhancing As(V) toxicity.

PMID- 22997024
TI  - Anti-Stokes fluorescence from endogenously formed protoporphyrin IX--implications
      for clinical multiphoton diagnostics.
AB  - Multiphoton imaging based on two-photon excitation is making its way into the
      clinics, particularly for skin cancer diagnostics. It has been suggested that
      endogenously formed protoporphyrin IX (PpIX) induced by aminolevulinic acid or
      methylaminolevulinate can be applied to improve tumor contrast, in connection to
      imaging of tissue autofluorescence. However, previous reports are limited to cell
      studies and data from tissue are scarce. No report shows conclusive evidence that
      endogenously formed PpIX increases tumor contrast when performing multiphoton
      imaging in the clinical situation. We here demonstrate by spectral analysis that
      two-photon excitation of endogenously formed PpIX does not provide additional
      contrast in superficial basal cell carcinomas. In fact, the PpIX signal is
      overshadowed by the autofluorescent background. The results show that PpIX should
      be excited at a wavelength giving rise to one-photon anti-Stokes fluorescence, to
      overcome the autofluorescent background. Thus, this study reports on a plausible
      method, which can be implemented for clinical investigations on endogenously
      formed PpIX using multiphoton microscopy.

PMID- 22997025
TI  - CO2 on a tightrope: stabilization, room-temperature decarboxylation, and sodium
      induced carboxylate migration.
AB  - A sterically shielded 3-substituted zwitterionic N,N-dimethylisotryptammonium
      carboxylate has been synthesized by consecutive chemoselective double alkylation
      of indole. The carboxylate undergoes a quantitative and unusually facile
      decarboxylation in dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF) at room
      temperature. The breaking of a nearly equidistant hydrogen bond by solvent
      molecules initiates heterolytic C-C cleavage. The decarboxylation rate decreases
      with increasing CO(2) partial pressure, proving the competitiveness of
      protonation and re-carboxylation of the carbanionic intermediate. Corresponding
      spiro compounds containing silylene and stannylene moieties show high thermal
      stability. Addition of an excess of methyllithium to the sodium salt triggers a
      reaction sequence comprising a deprotonation, carboxylate transfer, and
      nucleophilic trapping of the rearranged carboxylate by another equivalent of
      methyllithium. Hydrolytic work-up of the geminal diolate leads to an acetyl
      product. The role of the sodium counterion and the mechanism of the rearrangement
      have been unraveled by deuteration experiments.

PMID- 22997026
TI  - Evaluation of calcineurin/NFAT inhibitor selectivity in primary human Th cells
      using bar-coding and phospho-flow cytometry.
AB  - Small molecular inhibitors are excellent tools for manipulating cell reactions.
      They are widely used in scientific research to study molecular mechanisms of
      cells under physiological and pathophysiological conditions as well as in
      clinical applications to treat patients. However, their selectivity is often not
      well known. Moreover, it can vary according to cell types and the analysis
      methods used. Therefore, it is usually not possible to make comparisons between
      the data presented in the literature. Here we analyzed the selectivity of five
      chosen inhibitors of calcineurin/NFAT activation under the same conditions. Using
      a combination of fluorescent cell barcoding and phospho-specific flow cytometry
      we studied the inhibition of activation of NF-kappaBp65 and MAPK pathways in
      stimulated primary human Th cells. This semi-high throughput approach enabled us
      to demonstrate that (i) CsA and NCI3 are around 5 to 10- and 20-fold less potent,
      respectively, at inhibiting phosphorylation of NF-kappaBp65 and p38 than
      activation of NFAT, (ii) AM404 is at least 15-fold selective for NFAT but already
      toxic at concentrations above 40 MUM, (iii) INCA6 is not selective at all, and
      (iv) BTP1 is at least 100-fold selective for inhibition of NFAT activation
      relative to NF-kappaBp65, p38 and ERK1/2 phosphorylation. Altogether, our results
      not only show the applicability of a semi-high throughput inhibitor test system
      but also that BTP1 is the most selective inhibitor of calcineurin/NFAT activation
      among the studied inhibitors under the used conditions.

PMID- 22997027
TI  - Glycopeptide enrichment and separation for protein glycosylation analysis.
AB  - Protein glycosylation plays key roles in many biological processes. In addition,
      alterations in protein glycosylation have been related to different diseases, as
      well as may affect the properties of recombinant proteins used as human
      therapeutics. For this reason, protein glycosylation analysis is of main interest
      in biomedical and biopharmaceutical research. Although recent advances in LC-MS
      analysis have made possible glycoprotein glycosylation site identification,
      characterization of glycoprotein glycan structures, as well as glycoprotein
      identification and quantification, protein glycosylation analysis in complex
      samples still remains a difficult task. This is due to low proportions of
      glycopeptides in comparison to peptides obtained after glycoprotein digestion,
      the suppression of the glycopeptide MS signals in the presence of peptides, and
      the high heterogeneity of glycopeptides. Thus, in the recent years, continuous
      efforts have been devoted to the development of glycopeptide enrichment and
      separation strategies to facilitate and improve glycoprotein glycosylation
      analysis in complex samples. This review summarizes the different methodologies
      that can be employed for glycopeptide enrichment/separation from complex samples
      including methods based on lectin affinity enrichment, covalent interactions, or
      chromatographic separations and solid-phase extraction.

PMID- 22997028
TI  - Methodological aspects of sample preparation for the determination of carbamate
      residues: a review.
AB  - This review covers recent developments in sample preparations and analytical
      techniques for determination of residues of carbamate pesticides. Special
      attention is paid to the newly established microextraction techniques, including
      cloud-point extraction, dispersive liquid-liquid microextraction, and ultrasound
      assisted surfactant-enhanced emulsification microextraction. In addition,
      extractions using a variety of solvents, as well as miniaturized and on-line
      sample preparation systems, are discussed. Applications of the different methods
      for the determination of carbamate pesticide residues in food and environmental
      matrices are included.

PMID- 22997029
TI  - Mass transfer resistance in a liquid-phase microextraction employing a single
      hollow fiber under unsteady-state conditions.
AB  - In this study, the mass transport resistance in liquid-phase microextraction
      (LPME) in a single hollow fiber was investigated. A mathematical model has been
      developed for the determination of the overall mass transfer coefficient based on
      the acceptor phase in an unsteady state. The overall mass transfer coefficient in
      LPME in a single hollow fiber has been estimated from time-dependent
      concentration of extracted analyte in the acceptor phase while maintaining a
      constant analyte concentration in the donor phase. It can be achieved either
      using a high volume of donor to acceptor phase ratio or tuning the extraction
      conditions to obtain a low-enrichment factor, so that the analyte concentration
      in the sample is not significantly influenced by the mass transfer. Two
      extraction systems have been used to test experimentally the developed model: the
      extraction of Lu(III) from a buffer solution and the extraction of three local
      anesthetics from a buffer or plasma solution. The mass transfer resistance,
      defined as a reciprocal values of the mass transfer coefficient, was found to be
      1.2 * 10(3) cm(-1) min for Lu(III) under optimal conditions and from 1.96 to 3.3
      * 10(3) cm(-1) min for the local anesthetics depending on the acceptor pH and the
      hydrophobicity of the drug.

PMID- 22997030
TI  - A simplified approach to direct SPE-MS.
AB  - Microextraction by packed sorbent (MEPS) has been directly hyphenated with ESI-MS
      for the rapid screening of opiates and codeine metabolites in urine. This study
      introduces a novel format of MEPS that incorporates a two-way valve in the barrel
      of the syringe enabling the direction of liquid flow to be manipulated.
      Controlled directional flow (CDF) MEPS allows sharp, concentrated sample bands to
      be delivered directly to the MS in small volumes and effectively eliminates the
      need to optimize elution. The method optimization assessed the recovery, matrix
      effects, and the speed of infusion, all critical variables for optimum ESI
      performance. Matching extraction workflows demonstrated a reduction in carryover
      from 65% for conventional MEPS to only 1% for CDF MEPS. The recovery (<89% for 50
      MUL sample), matrix effects (<42%), linearity (r(2) > 0.99), and LODs (<5 ng/mL)
      were determined to demonstrate method performance. The optimized approach was
      employed for the screening of codeine metabolites in urine. The ion trace
      revealed sharp sample bands corresponding to the codeine metabolites. At-line
      MEPS-ESI-MS allowed both sample preparation and analysis to be completed in only
      5 min facilitating high throughput and alleviating the burden of method
      development.

PMID- 22997031
TI  - A membrane microcontactor as a tool for integrated sample preparation.
AB  - A membrane microcontactor suitable to perform liquid-liquid extraction as well as
      evaporation in order to conduct enrichment steps in sample preparation of organ
      samples has been designed, fabricated, and characterized. Spacers of 100- or 200
      MUm high were constructed in a metal substrate with a channel width of 13 mm and
      the extraction kinetics in these channels was evaluated. The spacers were
      designed such that at the entrance and exit region a uniform flow distribution
      could take place and that a uniform flow profile could be guaranteed along the
      channel, hence allowing a large freedom in sample volume to be processed. The
      extraction and evaporation kinetic behavior of the device was first evaluated by
      extraction of a drug candidate (4-(2,5-dimethyl-pyrrol-1-y1)-2-hydroxybenzoic
      acid). To evaluate the device under more challenging working conditions, a
      homogenized mice kidney sample containing the drug candidate that was
      administered in life condition was cleaned and enriched with the extraction and
      evaporation modules and characterized by high-performance liquid chromatography,
      yielding an overall analysis time of 15-20 min per sample only. The system has
      the potential to be operated in a continuous fashion, making it appealing to be
      implemented in screening or high-throughput applications.

PMID- 22997032
TI  - An optimized approach for enrichment of glycoproteins from cell culture lysates
      using native multi-lectin affinity chromatography.
AB  - Lectins are capable of recognizing specific glycan structures and serve as
      invaluable tools for the separation of glycosylated proteins from nonglycosylated
      proteins in biological samples. We report on the optimization of native multi
      lectin affinity chromatography, combining three lectins, namely, concanavalin A,
      jacalin, and wheat germ agglutinin for fractionation of cellular glycoproteins
      from MCF-7 breast cancer lysate. We evaluated several conditions for optimum
      recovery of total proteins and glycoproteins such as low pH and saccharide
      elution buffers, and the inclusion of detergents in binding and elution buffers.
      Optimum recovery was observed with overnight incubation of cell lysate with
      lectins at 4 degrees C, and inclusion of detergent in binding and saccharide
      elution buffers. Total protein and bound recoveries were 80 and 9%, respectively.
      Importantly, we found that high saccharide strength elution buffers were not
      necessary to release bound glycoproteins. This study demonstrates that multi
      lectin affinity chromatography can be extended to total cell lysate to
      investigate the cellular glycoproteome.

PMID- 22997033
TI  - Matrix solid-phase dispersion extraction followed by HPLC-diode array detection
      method for the determination of major constituents in a traditional Chinese
      medicine Folium isatidis (Da-qing-ye).
AB  - A simple and low-cost method based on matrix solid-phase dispersion (MSPD)
      extraction, HPLC separation, and diode array detection has been developed for the
      determination of indigo and indirubin in Folium isatidis. The experimental
      parameters that may affect the MSPD method, including dispersing sorbent, ratio
      of dispersing sorbent to sample, elution solvent, and volume of the elution
      solvent were examined and optimized. The optimized conditions were determined to
      be that C18 was used as dispersing sorbent, the ratio of C18 to sample mass was
      selected to be 4:1, and 10 mL of N,N-dimethyl formamide was used as elution
      solvent. The highest extraction yields of the two compounds were obtained under
      the optimized conditions. The method showed good linearity (r > 0.9995) and
      precision (RSD < 3.0%) for indigo and indirubin, with the limits of detection of
      18 and 22.5 ng/mL, respectively. The recoveries were in the range of 90.33
      100.74% with RSD values ranging from 1.7 to 3.6%. Comparing to ultrasonic and
      Soxhlet methods, the proposed MSPD procedure was more convenient and less time
      consuming with reduced requirements on sample and solvent amounts. The proposed
      procedure was applied to analyzed three real samples that were collected from
      different localities.

PMID- 22997034
TI  - Pre-concentration of non-steroidal anti-inflammatory drugs in water using
      dispersive liquid-liquid and single-drop microextraction with high-performance
      liquid chromatography.
AB  - In the present work the combination of two liquid-phase microextraction
      techniques involving dispersive liquid-liquid microextraction and single-drop
      microextraction as a new pre-concentration technique is developed for the
      separation and determination of acidic non-steroidal anti-inflammatory
      pharmaceutical compounds, namely, naproxen, diclofenac, and ibuprofen, in water
      samples using high-performance liquid chromatography ultra violet-detection. The
      extraction conditions were optimized and, under the optimal conditions, the
      method showed good linearity range of 0.1-1000 MUg L(-1)  (R > 0.9990),
      acceptable reproducibilities (relative standard deviation% = 4.5-8.8%), low
      limits of detection (0.03-0.2 MUg L(-1) ), and satisfactory relative recoveries.
      The developed method was applied for the determination of anti-inflammatory drugs
      in river and waste water samples.

PMID- 22997035
TI  - Rapid analysis of polybrominated diphenyl ethers in soil by matrix solid-phase
      dispersion using bamboo charcoal as dispersive sorbent.
AB  - An expeditious and sensitive method for the analysis of eight major
      polybrominated diphenyl ethers (PBDEs) in soil is presented in this study. The
      method is based on matrix solid-phase dispersion (MSPD) extraction and gas
      chromatography with negative chemical ionization mass spectrometry. Bamboo
      charcoal, a cheap and potentially useful material, was selected for the first
      time as the MSPD dispersive sorbent. Parameters affecting the extraction
      efficiency, including the ratio of sorbent to sample, and the type and amount of
      eluent, were investigated and optimized in detail. Under optimal conditions, the
      spiked recovery of the PBDEs was in the range 71.7-105.9%, and the limits of
      detection varied from 10 to 400 pg g(-1) (dry weight). Excellent linearity with
      correlation coefficients (r(2)) of 0.9992-0.9999 was obtained over the
      concentration range of 0.10-500 ng g(-1) , except for BDE-209, for which the
      effective concentration range was 1.0-5000 ng g(-1) . The developed method has
      been successfully applied to the analysis of PBDEs in real soil samples.

PMID- 22997036
TI  - Ionic liquid-based vortex-assisted dispersive liquid-liquid microextraction of
      organophosphorus pesticides in apple and pear.
AB  - An ionic liquid-based vortex-assisted dispersive liquid-liquid microextraction
      (DLLME) was developed for the analysis of trace amounts of six organophosphorus
      pesticides (OPPs) in apple and pear coupled with high-performance liquid
      chromatography. During the DLLME, the effect of some experimental factors
      including extraction solvent and its volume, dispersion solvent and its volume,
      vortex time, salt addition, and pH on the extraction procedure were investigated.
      Under the chosen extraction conditions, the analytes were enriched more than 300
      fold and the limits of detections were greatly dropped to 0.061-0.73 MUg/kg. The
      linearity relationship was observed in the range of 2-100 MUg/kg with the
      correlation coefficients (R(2)) ranging from 0.9967 to 0.9983. The relative
      standard deviations varied from 2.3 to 5.7% (n = 6). Mean recovery values of the
      OPPs were in the range of 69.8-109.1% with a relative standard deviation lower
      than 7.0%. Based on these above, it could be concluded that 1-octyl-3
      methylimidazolium hexafluorophosphate ([C(8)MIM][PF(6)]) was a good extraction
      solvent and the proposed [C(8)MIM][PF(6)]-based vortex-assisted DLLME method was
      suitable for the effective extraction of the OPPs in apple and pear.

PMID- 22997039
TI  - Sample preparation--a modern and complex field.

PMID- 22997041
TI  - Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu
      transgenic mice.
AB  - Human epidermal growth factor receptor 2 (HER2) overexpression leads to mammary
      tumorigenesis and its elevated levels lead to increase in cancer stem cells
      (CSCs), invasion, and metastasis. CSCs are resistant to
      radiation/chemotherapeutic drugs and are believed to be responsible for
      recurrence/relapse of cancer. CSCs are isolated using flow cytometry based
      sorting, although reliable, this technology hinders the convenient identification
      of molecular targets of CSCs. Therefore to understand the molecular players of
      increased CSC through HER2 overexpression and to develop meaningful targets for
      combination therapy, we isolated and characterized breast CSCs through convenient
      tumorsphere culture. We identified the altered protein expression in CSC as
      compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and
      Western blotting. Ferritin heavy chain 1 (FTH1) was identified as a candidate
      gene, which is involved in iron metabolism and iron depletion significantly
      decreased the self-renewal of CSCs. We further performed in silico analysis of
      altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6,
      TNXRD1, COX-1, COX-2, KRT14, and FTH1), representing possible molecular targets,
      which in combination showed a promise to be used as prognostic markers for breast
      cancer.

PMID- 22997040
TI  - Concise review: Can stem cells be used to treat or model Alzheimer's disease?
AB  - Alzheimer's disease (AD) is the leading cause of age-related dementia, affecting
      over 5 million people in the U.S. alone. AD patients suffer from progressive
      neurodegeneration that gradually impairs their memory, ability to learn, and
      carry out daily activities. Unfortunately, current therapies for AD are largely
      palliative and several promising drug candidates have failed in recent clinical
      trials. There is therefore an urgent need to improve our understanding of AD
      pathogenesis, create innovative and predictive models, and develop new and
      effective therapies. In this review, we will discuss the potential of stem cells
      to aid in these challenging endeavors. Because of the widespread nature of AD
      pathology, cell-replacement strategies have been viewed as an incredibly
      challenging and unlikely treatment approach. Yet recent work shows that
      transplantation of neural stem cells (NSCs) can improve cognition, reduce
      neuronal loss, and enhance synaptic plasticity in animal models of AD.
      Interestingly, the mechanisms that mediate these effects appear to involve
      neuroprotection and trophic support rather than neuronal replacement. Stem cells
      may also offer a powerful new approach to model and study AD. Patient-derived
      induced pluripotent stem cells, for example, may help to advance our
      understanding of disease mechanisms. Likewise, studies of human embryonic and
      NSCs are helping to decipher the normal functions of AD-related genes; revealing
      intriguing roles in neural development.

PMID- 22997042
TI  - Cooperation of two bifunctional enzymes in the biosynthesis and attachment of
      deoxysugars of the antitumor antibiotic mithramycin.
AB  - Two bifunctional enzymes cooperate in the assembly and the positioning of two
      sugars, D-olivose and D-mycarose, of the anticancer antibiotic mithramycin. MtmC
      finishes the biosynthesis of both sugar building blocks depending on which MtmGIV
      activity is supported. MtmGIV transfers these two sugars onto two structurally
      distinct acceptor substrates. The dual function of these enzymes explains two
      essential but previously unidentified activities.

PMID- 22997043
TI  - The adolescent female: Breast and reproductive embryology and anatomy.
AB  - Congenital breast and genital tract anomalies are seen frequently in the care of
      children and adolescents. Breast and internal gynecologic anomalies more often
      present in adolescence than in early childhood. Management is best delivered
      through a multidisciplinary team approach. Carefully timed surgical intervention
      is of importance to optimize psychological, aesthetic and functional outcomes. An
      understanding of the female breast and genital tract embryology and anatomy is
      important for a meticulous clinical examination and appropriate surgical
      treatment. This article will review the normal embryology and anatomy of the
      adolescent female breast and genital tract.

PMID- 22997044
TI  - Antibacterial soybean-oil-based cationic polyurethane coatings prepared from
      different amino polyols.
AB  - Antibacterial soybean-oil-based cationic polyurethane (PU) coatings have been
      successfully prepared from five different amino polyols. The structure and
      hydroxyl functionality of these amino polyols affects the particle morphology,
      mechanical properties, thermal stability, and antibacterial properties of the
      resulting coatings. An increase in the hydroxyl functionality of the amino
      polyols increases the cross-link density, resulting in an increased glass
      transition temperature and improved mechanical properties. Both the cross-link
      density and the amount of ammonium cations incorporated into the PU backbone
      affect the thermal stability of PU films. PUs with the lowest ammonium cation
      content and highest cross-link density exhibit the best thermal stability. With
      some strain-specific exceptions, these PUs show good antibacterial properties
      toward a panel of bacterial pathogens comprised of Listeria monocytogenes NADC
      2045, Salmonella typhimurium ATCC 13311 and Salmonella minnesota (S. minnesota)
      R613. S. minnesota R613 is a "deep rough" mutant lacking a full outer membrane
      (OM) layer, an important barrier structure in gram-negative bacteria. With wild
      type strains, the PU coatings exhibit better antibacterial properties toward the
      gram-positive Listeria monocytogenes than the gram-negative S. minnesota.
      However, the coatings have excellent activity against S. minnesota R613,
      suggesting a protective role for an intact OM against the action of these PUs.

PMID- 22997045
TI  - Pressure to keep up macho image might be behind rise in suicides among men.

PMID- 22997046
TI  - Swedish surgeons report world's first uterus transplantations from mother to
      daughter.

PMID- 22997047
TI  - Mechanistic studies on the gas-phase dehydrogenation of alkanes at cyclometalated
      platinum complexes.
AB  - In the ion/molecule reactions of the cyclometalated platinum complexes [Pt(L
      H)](+) (L=2,2'-bipyridine (bipy), 2-phenylpyridine (phpy), and 7,8-benzoquinoline
      (bq)) with linear and branched alkanes C(n)H(2n+2) (n=2-4), the main reaction
      channels correspond to the eliminations of dihydrogen and the respective alkenes
      in varying ratios. For all three couples [Pt(L-H)](+)/C(2)H(6), loss of C(2)H(4)
      dominates clearly over H(2) elimination; however, the mechanisms significantly
      differs for the reactions of the "rollover"-cyclometalated bipy complex and the
      classically cyclometalated phpy and bq complexes. While double hydrogen-atom
      transfer from C(2)H(6) to [Pt(bipy-H)](+), followed by ring rotation, gives rise
      to the formation of [Pt(H)(bipy)](+), for the phpy and bq complexes [Pt(L-H)](+),
      the cyclometalated motif is conserved; rather, according to DFT calculations,
      formation of [Pt(L-H)(H(2))](+) as the ionic product accounts for C(2)H(4)
      liberation. In the latter process, [Pt(L-H)(H(2))(C(2)H(4))](+) (that carries
      H(2) trans to the nitrogen atom of the heterocyclic ligand) serves, according to
      DFT calculation, as a precursor from which, due to the electronic peculiarities
      of the cyclometalated ligand, C(2)H(4) rather than H(2) is ejected. For both
      product-ion types, [Pt(H)(bipy)](+) and [Pt(L-H)(H(2))](+) (L=phpy, bq), H(2)
      loss to close a catalytic dehydrogenation cycle is feasible. In the reactions of
      [Pt(bipy-H)](+) with the higher alkanes C(n)H(2n+2) (n=3, 4), H(2) elimination
      dominates over alkene formation; most probably, this observation is a consequence
      of the generation of allyl complexes, such as [Pt(C(3)H(5))(bipy)](+). In the
      reactions of [Pt(L-H)](+) (L=phpy, bq) with propane and n-butane, the losses of
      the alkenes and dihydrogen are of comparable intensities. While in the reactions
      of "rollover"-cyclometalated [Pt(bipy-H)](+) with C(n)H(2n+2) (n=2-4) less than
      15 % of the generated product ions are formed by C-C bond-cleavage processes,
      this value is about 60 % for the reaction with neo-pentane. The result that C-C
      bond cleavage gains in importance for this substrate is a consequence of the fact
      that 1,2-elimination of two hydrogen atoms is no option; this observation may
      suggest that in the reactions with the smaller alkanes, 1,1- and 1,3-elimination
      pathways are only of minor importance.

PMID- 22997048
TI  - Students aggress against professors in reaction to receiving poor grades: an
      effect moderated by student narcissism and self-esteem.
AB  - Laboratory evidence about whether students' evaluations of teaching (SETs) are
      valid is lacking. Results from three (3) independent studies strongly confirm
      that "professors" who were generous with their grades were rewarded for their
      favor with higher SETs, while professors who were frugal were punished with lower
      SETs (Study 1, d = 1.51; Study 2, d = 1.59; Study 3, partial eta(2) = .26). This
      result was found even when the feedback was manipulated to be more or less
      insulting (Study 3). Consistent with laboratory findings on direct aggression,
      results also indicated that, when participants were given a poorer feedback,
      higher self-esteem (Study 1 and Study 2) and higher narcissism (Study 1) were
      associated with them giving lower (more aggressive) evaluations of the
      "professor." Moreover, consistent with findings on self-serving biases,
      participants higher in self-esteem who were in the positive grade/feedback
      condition exhibited a self-enhancing bias by giving their "professor" higher
      evaluations (Study 1 and Study 2). The aforementioned relationships were not
      moderated by the professor's sex or rank (teaching assistant vs.professor).
      Results provide evidence that (1) students do aggress against professors through
      poor teaching evaluations, (2) threatened egotism among individuals with high
      self-esteem is associated with more aggression, especially when coupled with high
      narcissism, and (3) self-enhancing biases are robust among those with high self
      esteem.

PMID- 22997049
TI  - The hitchhikers guide to cancer stem cell theory: markers, pathways and therapy.
AB  - Cancer stem cell (CSC) biology is a rapidly developing field within cancer
      research. CSCs are postulated to be a unique cell population exclusively capable
      of infinite self renewal, multilineage differentiation and with ability to evade
      conventional cytotoxic cancer therapy. These traits distinguish CSCs from their
      more differentiated counterparts, which possess only limited or no potential for
      self renewal and tumor initiation. Therefore, CSCs would be the driving motor of
      malignant growth and therapy resistance. Accordingly, successful cancer treatment
      would need to eliminate this highly potent group of cells, since even small
      residual numbers would suffice to recapitulate the disease after therapy.
      Putative CSCs has been identified in a broad range of human malignancies and
      several cell surface markers have been associated with their stem cell phenotype.
      Despite all efforts, a pure CSC population has not been isolated and often in
      vitro clonogenic and in vivo tumorigenic potential is found in several cell
      populations with occasionally contradictory surface marker signatures. Here, we
      give a brief overview of recent advances in CSC theory, including the signaling
      pathways in CSCs that also appear crucial for stem cells homeostasis in normal
      tissues. We discuss evidence for the interaction of CSCs with the stromal tumor
      environment. Finally, we review the emerging potentially effective CSC-targeted
      treatment strategies and their future role in therapy.

PMID- 22997050
TI  - An approach for calculating a confidence interval from a single aquatic sample
      for monitoring hydrophobic organic contaminants.
AB  - The use of passive sampling devices (PSDs) for monitoring hydrophobic organic
      contaminants in aquatic environments can entail logistical constraints that often
      limit a comprehensive statistical sampling plan, thus resulting in a restricted
      number of samples. The present study demonstrates an approach for using the
      results of a pilot study designed to estimate sampling variability, which in turn
      can be used as variance estimates for confidence intervals for future n = 1 PSD
      samples of the same aquatic system. Sets of three to five PSDs were deployed in
      the Portland Harbor Superfund site for three sampling periods over the course of
      two years. The PSD filters were extracted and, as a composite sample, analyzed
      for 33 polycyclic aromatic hydrocarbon compounds. The between-sample and within
      sample variances were calculated to characterize sources of variability in the
      environment and sampling methodology. A method for calculating a statistically
      reliable and defensible confidence interval for the mean of a single aquatic
      passive sampler observation (i.e., n = 1) using an estimate of sample variance
      derived from a pilot study is presented. Coverage probabilities are explored over
      a range of variance values using a Monte Carlo simulation.

PMID- 22997051
TI  - Prognostic biomarkers of survival in oropharyngeal squamous cell carcinoma:
      systematic review and meta-analysis.
AB  - BACKGROUND: Human papillomavirus (HPV) positivity improves prognosis in patients
      with oropharyngeal squamous cell carcinoma (OPSCC). Combining HPV status with
      other biomarkers may improve its prognostic power. METHODS: The approach was a
      literature search for longitudinal studies of biomarkers in OPSCC, with
      systematic review and meta-analysis. RESULTS: In all, 3130 articles were
      identified; 32 satisfied the inclusion and exclusion criteria. On meta-analysis,
      there was a significant overall survival (OS) benefit for patients with HPV
      positive and p16 positive tumors. There was some evidence of improved OS of OPSCC
      patients with raised bcl2; amplification of 11q3 and loss of 16q genes; and low c
      met, ki67, IMD, PLK, FHIT, nuclear surviving, or nuclear cyclin D1. However, none
      of these was suitable for meta-analysis. CONCLUSION: Survival from OPSCC is
      associated with several biomarkers, which constitute potential targets for
      research into improving the prognostic power of HPV in OPSCC. Larger trials are
      needed, with standardization of cut-points and adherence to consensus reporting
      guidelines.

PMID- 22997053
TI  - Imaging depletion: fMRI provides new insights into the processes underlying ego
      depletion*.
AB  - 'Ego depletion' refers to the phenomenon of diminished ability to enact self
      regulation with repeated efforts. Several models offer process accounts of how
      ego depletion works, but few studies directly investigate these processes. A
      study in this issue of Social, Cognitive, & Affective Neuroscience by Wagner and
      Heatherton is among the first to do so. Their results substantiate one possible
      mechanism of ego depletion and, more broadly, illustrate how neuroscience data
      can further social psychological theory.

PMID- 22997052
TI  - Magnesium methoxide-induced chemiluminescent decomposition of bicyclic dioxetanes
      bearing a 2'-alkoxy-2-hydroxy-1,1'-binaphthyl-7-yl moiety.
AB  - Bicyclic dioxetanes 2a-c bearing a 2'-alkoxy-2-hydroxy-1,1'-binaphthyl-7-yl
      moiety were effectively synthesized and their base-induced chemiluminescent
      decomposition was investigated by the use of alkaline metal (Na(+) and K(+) ) or
      Mg(2+) alkoxide in MeOH. When 2a-c were treated with tetrabutylammonium fluoride
      (TBAF) in dimethyl sulfoxide (DMSO) as a reference system, they showed
      chemiluminescence as a flash of orange light (maximum wavelength lambdamax (CL) 
      = 573-577 nm) with efficiency Phi(CL)  = 6-8 * 10(-2) . On the other hand, for an
      alkaline metal (Na(+) or K(+) ) alkoxide/MeOH system, 2a-c decomposed slowly to
      emit a glow of chemiluminescence, the spectra of which were shifted slightly
      toward red from the TBAF/DMSO system, and Phi(CL) (= 1.4-2.3 * 10(-3) ) was
      considerably decreased. In addition, Mg(OMe)2 was found to play a characteristic
      role as a base for the chemiluminescent decomposition of 2a-c through
      coordination to the intermediary oxidoaryl-substituted dioxetanes 13. Thus,
      Mg(2+) increased Phi(CL) to more than twice those with Na(+) or K(+) , while it
      shifted lambdamax (CL) considerably toward blue (lambdamax (CL)  = 550-566 nm).

PMID- 22997055
TI  - Simultaneous preconcentration and determination of 2,4-D, alachlor and atrazine
      in aqueous samples using dispersive liquid-liquid microextraction followed by
      high-performance liquid chromatography ultraviolet detection.
AB  - Dispersive liquid-liquid microextraction coupled with high-performance liquid
      chromatography-ultraviolet detection as a fast and inexpensive technique was
      applied to the simultaneous extraction and determination of traces of three
      common herbicides, 2,4-D, alachlor and atrazine, in aqueous samples. The critical
      experimental parameters, including type of the extraction and disperser solvents
      as well as their volumes, sample pH, salt addition, extraction time and
      centrifuging time, and speed were investigated and optimized. Under the optimum
      conditions, the calibration graphs found to be linear in the range of 0.3-200
      MUg/L with limits of detection in the range of 0.05-0.1 MUg/L. The relative
      standard deviations were in the range of 4.5-6.2% (n = 7). The relative
      recoveries of well, tap, and river water samples which have been spiked with
      different levels of herbicides were 92.0-107.0, 82.0-104.0, and 82.0-86.0%,
      respectively.

PMID- 22997054
TI  - Branding and a child's brain: an fMRI study of neural responses to logos.
AB  - Branding and advertising have a powerful effect on both familiarity and
      preference for products, yet no neuroimaging studies have examined neural
      response to logos in children. Food advertising is particularly pervasive and
      effective in manipulating choices in children. The purpose of this study was to
      examine how healthy children's brains respond to common food and other logos. A
      pilot validation study was first conducted with 32 children to select the most
      culturally familiar logos, and to match food and non-food logos on valence and
      intensity. A new sample of 17 healthy weight children were then scanned using
      functional magnetic resonance imaging. Food logos compared to baseline were
      associated with increased activation in orbitofrontal cortex and inferior
      prefrontal cortex. Compared to non-food logos, food logos elicited increased
      activation in posterior cingulate cortex. Results confirmed that food logos
      activate some brain regions in children known to be associated with motivation.
      This marks the first study in children to examine brain responses to culturally
      familiar logos. Considering the pervasiveness of advertising, research should
      further investigate how children respond at the neural level to marketing. 

PMID- 22997056
TI  - Simultaneous extraction and rapid visualization of peptidomic and lipidomic body
      fluids fingerprints using mesoporous aluminosilicate and MALDI-TOF MS.
AB  - Herein we report the use of mesoporous aluminosilicate (MPAS) for the
      simultaneous extraction of peptides and lipids from complex body fluids such as
      human plasma and synovial fluid. We show that MPAS particles, given their
      mesostructural features with nanometric pore size and high surface area, are an
      efficient device for simultaneous extraction of peptidome and lipidome from as
      little as a few microliters of body fluids. The peptides and the lipids, selected
      and enriched by MPAS particles and rapidly visualized by MALDI-TOF MS, could form
      part of a diagnostic profile of the "peptidome" and the "lipidome" of healthy
      versus diseased subjects in comparative studies. The ability of this approach to
      rapidly reveal the overall pattern of changes in both lipidome and peptidome
      signatures of complex biofluids could be of valuable interest for handling large
      numbers of samples required in -omics studies for the purpose of finding novel
      biomarkers.

PMID- 22997057
TI  - Categorizing the distribution of the saphenous nerve in relation to the great
      saphenous vein.
AB  - Saphenous donor site neuralgia is a cause of morbidity post-coronary artery
      bypass surgery. Saphenous nerve damage during harvesting of the great saphenous
      vein is thought to be responsible. We dissected 37 cadaveric lower limbs from the
      knee fold to the dorsal venous arches, to study the spatial relations of the
      saphenous nerve and great saphenous vein to identify its distribution within the
      leg. Distribution of the saphenous nerve was categorized into Type A, where the
      nerve traveled inferiorly and split into an anterior and posterior branch during
      its course between the knee fold and medial malleolus, Type B, where the nerve
      traveled anterior to the vein with a small caliber branch traveling posteriorly
      at the proximal end, Type C where two main branches originated at the knee fold,
      one anterior to and one posterior to the vein. Overall the vein and nerve crossed
      in 27 out of the 37 cases (73%), occurring between 5 and 29 cm from the malleolus
      (60% occurred between 16 and 26 cm). In 32 (86%) of cases, the distal part of the
      nerve and vein were tightly adhered to each other within a common sheath. The
      length of adherence ranged from 3 to 26 cm with an average of 14 cm. The
      saphenous nerve is highly vulnerable during harvesting of the great saphenous
      vein due to its close relationship and crossing branches. Knowledge of the
      distribution categories of the nerve can help guide the surgeon to avoid damaging
      nerve branches during harvesting.

PMID- 22997058
TI  - Polysaccharides immobilized in polypyrrole matrices are able to induce osteogenic
      differentiation in mouse mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (MSCs) have attracted considerable interest
      due to their ability to differentiate and contribute to the regeneration of
      mesenchymal tissues. The present study illustrates that the proper immobilization
      of heparin (Hep) and hyaluronic acid (HA) into a polypyrrole (PPy) matrix by
      electropolymerization results in an optimal interface for MSC differentiation
      towards osteoblast lineage. The obtained thin films showed good thermal
      stability, hydrophilicity and slow controlled polysaccharide release. The in
      vitro tests showed the main role of the interface chemical composition. Indeed,
      PPyHep and PPyHA thin films were able to induce osteogenic differentiation as
      determined by levels of specific early osteogenic markers (Runx2 and osterix)
      even in the absence of differentiating medium. Increased levels of ALP and
      Alizarin red staining, both indicating mineralization processes, confirmed the
      presence of mature osteoblasts.

PMID- 22997059
TI  - The ortho and meta magnesiation of functionalized anilines and amino-substituted
      pyridines and pyrazines at room temperature.
AB  - A practical ortho,meta, (or even ortho,ortho') magnesiation of
      trifluoroacetamides of anilines, aminopyridines, and aminopyrazines at room
      temperature was performed with TMPMgCl?LiCl or TMP(2) Mg?2 LiCl. These
      magnesiations are compatible with several carbonyl functionalities and allow
      access to polysubstituted anilides in satisfactory yields.

PMID- 22997060
TI  - Comparison of emetic potencies of the 8-ketotrichothecenes deoxynivalenol, 15
      acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X, and nivalenol.
AB  - Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol (DON
      or vomitoxin), a known cause of human food poisoning, have been well
      characterized in several animal species, much less is known about closely related
      8-ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic
      fusaria. To address this, we compared potencies of DON, 15-acetyldeoxynivalenol
      (15-ADON), 3-acetyldeoxynivalenol (3-ADON), fusarenon X (FX), and nivalenol (NIV)
      in the mink emesis model following intraperitoneal (ip) and oral administration.
      All five congeners dose-dependently induced emesis by both administration
      methods. With increasing doses, there were marked decreases in latency to emesis
      with corresponding increases in emesis duration and number of emetic events. The
      effective doses resulting in emetic events in 50% of the animals for ip exposure
      to DON, 15-ADON, 3-ADON, FX, and NIV were 80, 170, 180, 70, and 60 ug/kg bw,
      respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 ug/kg bw,
      respectively. The emetic potency of DON determined here was comparable to that
      reported in analogous studies conducted in pigs and dogs, suggesting that the
      mink is a suitable small animal model for investigating acute trichothecene
      toxicity. The use of a mouse pica model, based on the consumption of kaolin, was
      also evaluated as a possible surrogate for studying emesis but was found
      unsuitable. From a public health perspective, comparative emetic potency data
      derived from small animal models such as the mink should be useful for
      establishing toxic equivalency factors for DON and other trichothecenes.

PMID- 22997062
TI  - ZnO, SiO2, and SrO doping in resorbable tricalcium phosphates: Influence on
      strength degradation, mechanical properties, and in vitro bone-cell material
      interactions.
AB  - To understand the combined effects of ZnO, SiO(2), and SrO doping on mechanical
      and biological properties of tricalcium phosphate (TCP) ceramics, dense beta-TCP
      compacts of different compositions (pure beta-TCP; 1.0 wt % SrO; 0.25 wt % ZnO;
      1.0 wt % SrO + 0.5 wt % SiO(2); and 1.0 wt % SrO + 0.25 wt % ZnO) were prepared
      via dry pressing followed by sintering at 1250 degrees C. X-ray diffraction of
      sintered compacts revealed that dopants retarded beta- to alpha-TCP phase
      transformation during sintering. Doping with SrO, SrO/SiO(2), and SrO/ZnO reduced
      compressive strength of the samples to 56% (173 +/- 25 MPa), 57% (170 +/- 15
      MPa), and 47% (208 +/- 72 MPa) of pure beta-TCP (396 +/- 58 MPa), respectively.
      However, addition of ZnO resulted in only 7% (365 +/- 69 MPa) strength
      degradation. The impact of dopants on long-term in vitro strength degradation was
      evaluated by soaking in simulated body fluid (SBF) for a period of 8 weeks. In
      all cases, excellent apatite growth was observed on doped beta-TCP samples.
      However, strength degradation rates were different depending on dopant chemistry
      and composition. Maximum degradation was observed in undoped and ZnO-doped beta
      TCP samples, which degraded to 41% and 68% of the original strength before
      soaking in SBF. Finally, in vitro cell-materials interaction study using human
      fetal osteoblast cells demonstrated that addition of dopants improved cell
      attachment and proliferation. These results indicate that tailorable strength and
      strength degradation behavior can be achieved in beta-TCP via compositional
      modifications using small amount of dopants.

PMID- 22997063
TI  - Plasma and red cell exchange transfusions for erythropoietic protoporphyria: a
      case report and review of the literature.
AB  - Erythropoietic protoporphyria (EPP) is a rare and usually autosomal dominant
      disorder characterized by ferrochelatase deficiency and accumulation of
      protoporphyrin in red blood cells (RBCs), skin, and liver. A small minority of
      patients develop severe liver dysfunction for which optimum treatment is lacking.
      Therapeutic plasma exchange (TPE) and RBC exchange (RCE) have been anecdotally
      reported to benefit patients with EPP and liver failure. A 50-year-old female
      with EPP developed severe liver dysfunction after knee replacement surgery and
      high-dose acetaminophen use. Liver biopsy showed cholestatic liver injury without
      fibrosis. A total of 20 TPE procedures, six RCE procedures, and then 14 more TPE
      procedures were performed as adjunctive therapy with the purpose of preventing
      progression to end-stage liver failure. After initial TPE, the plasma and RBC
      protoporphyrin levels decreased from 834.9 to 180.4 MUg/dL (normal, <=1 MUg/dL),
      and from 3,905 to 2,879 MUg/dL (normal, <=80 MUg/dL), respectively, without liver
      function improvement. RCE decreased RBC protoporphyrin levels from 2,879 to 1,225
      MUg/dL but plasma protoporphyrin increased from 180.4 to 1,044.1 MUg/dL, and
      liver function failed to improve. Additional TPE again stabilized plasma
      protoporphyrin and improved RBC protoporphyrin levels but the patient ultimately
      died owing to end-stage liver disease complications. This case illustrates that
      TPE and RCE may improve the plasma and RBC biochemical markers of EPP activity
      but liver function abnormalities may persist and patients may still progress to
      liver failure either because of irreversible liver injury or independent
      pathobiological factors unrelated to EPP-induced hepatotoxicity.

PMID- 22997064
TI  - Telomere length and LINE1 methylation is associated with chromosomal aberrations
      in peripheral blood.
AB  - The frequency of chromosomal aberrations in peripheral blood predicts a probable
      cancer risk. The individual telomere length and methylation of repetitive
      elements may be susceptibility factors for chromosomal aberrations. A cohort of
      healthy Norwegian men (N = 364) recruited during 1980-1999 were analyzed for
      chromosomal aberrations in phytohemagglutinin-stimulated lymphocytes from
      peripheral blood. Chromosome-type or chromatid-type aberrations were scored. DNA
      was extracted from slides cytogenetically analyzed and relative average telomere
      length and methylation of LINE1 repeats were determined by quantitative
      polymerase chain reaction and bisulfite pyrosequencing, respectively. Information
      about individuals with malignant tumors (N = 49) diagnosed after chromosomal
      aberrations testing until end of 2008 was obtained and two matched controls per
      case were used in a nested case-control analysis. Shorter relative telomere
      length and higher methylation of LINE1 were associated with higher frequency of
      total chromosomal aberrations (beta = -0.76, P = 0.022; and beta = 0.042, P =
      0.048, respectively; age-adjusted ordinal regression). The telomere length was
      stronger associated with chromosome-type (beta = -1.00, P = 0.006) than with
      chromatid-type aberrations (beta = -0.49, P = 0.115). The LINE1 methylation was
      stronger associated with chromatid-type (beta = 0.062, P = 0.003) than with
      chromosome-type aberrations (beta = 0.018, P = 0.41). Telomere length
      [individuals with short telomeres odds ratio (OR) = 0.87, 95% confidence interval
      (CI) 0.38-2.0], LINE1 (individuals with high methylation OR = 1.04, 95% CI 0.43
      2.5) and chromosomal aberrations (individuals with high frequency OR = 1.6, 95%
      CI 0.63-3.9) at baseline did not predict cancer risk, but the conclusions were
      hampered by low statistical precision. The results suggest that shorter telomere
      length and higher LINE1 methylation in peripheral blood lymphocytes are
      predisposition factors for increased frequency of chromosomal aberrations.

PMID- 22997065
TI  - International Atomic Energy Agency study with referring physicians on patient
      radiation exposure and its tracking: a prospective survey using a web-based
      questionnaire.
AB  - OBJECTIVES: To assess the following themes among referring physicians: (A)
      importance of acquiring information about previous diagnostic exposures; (B)
      knowledge about radiation doses involved, familiarity with radiation units and,
      age-related radiosensitivity; (C) opinion on whether patients should be provided
      information about radiation dose and (D) self-assessment of appropriateness of
      referrals. DESIGN: A prospective survey using a web-based questionnaire. SETTING:
      International survey among referring physicians. PARTICIPANTS: Referring
      physicians from 28 countries. MAIN OUTCOME MEASURES: Knowledge, opinion and
      practice of the four themes of the survey. RESULTS: All 728 responses from 28
      countries (52.3% from developed and 47.7% from developing countries) indicated
      that while the vast majority (71.7%) of physicians feel that being aware of
      history of CT scans would always or mostly lead them to a better decision on
      referring patients for CT scans, only 43.4% often enquire about it. The majority
      of referring physicians (60.5%) stated that having a system that provides quick
      information about patient exposure history would be useful. The knowledge about
      radiation doses involved is poor, as only one-third (34.7%) of respondents chose
      the correct option of the number of chest x-rays with equivalence of a CT scan.
      In total, 70.9% of physicians stated that they do not feel uncomfortable when
      patients ask about radiation risk from CT scans they prescribe. Most physicians
      (85.6%) assessed that they have rarely prescribed CT scans of no clinical use in
      patient management. CONCLUSIONS: This first ever multinational survey among
      referring physicians from 28 countries indicates support for a system that
      provides radiation exposure history of the patient, demonstrates poor knowledge
      about radiation doses, supports radiation risk communication with patients and
      mandatory provisions for justification of a CT examination.

PMID- 22997066
TI  - Ability of NIRS technology to determine pesticides in liquid samples at maximum
      residue levels.
AB  - BACKGROUND: Pesticide residues remaining on food represent a potential risk to
      consumer's health. Determination of these pesticide residues involves tedious
      procedures of analysis with regard to time and laboratory work. Near-infrared
      spectroscopy (NIRS) is a possible alternative to these methods. The aim of this
      research was to evaluate the ability of NIRS to classify two pesticides used for
      controlling apple fruit pests according to their concentration. Different
      solutions were prepared, based on the dose recommended by the pesticide producers
      for apple pest treatments. Spectra were acquired on a spectrophotometer from
      liquid samples belonging to these solutions. RESULTS: Calibration models were
      developed from liquid samples, following the soft independent modelling of class
      analogy (SIMCA) analysis method. These models classified between 99 and 100% of
      the validation samples belonging to different pesticide concentration solutions
      even at the maximum residue limit level of these products in apple fruit.
      CONCLUSIONS: NIRS technology shows a high potential for identifying pesticides in
      liquid samples, according to their concentration, at the levels required by the
      legislation.

PMID- 22997067
TI  - Mass spectrometric characterization of recombinant rat 5-hydroxytryptamine
      receptor 1A (5-HT(1A) R) expressed in tsA201 human embryonic kidney cells.
AB  - The 5-hydroxytryptamine 1A receptor (serotonin 1A receptor; 5-HT(1A) R) is
      involved in a large series of brain functions, and roles in anxiety, depression,
      and cognition have been reported. So far, published information on mass
      spectrometrical characterization of 5-HT(1A) R is limited to the presence of two
      5-HT(1A) R peptides in rat's whole brain as observed by in-solution digestion
      followed by LC-MS/MS. Knowledge about the protein sequence and PTMs, however,
      would have implications for generation of specific antibodies and designing
      studies on the 5-HT(1A) R at the protein level. A rat recombinant 5-HT(1A) R was
      extracted from the tsA201 cell line, run using several gel-based principles with
      subsequent in-gel digestion with several proteases, chymotrypsin, trypsin, AspN,
      proteinase K, and pepsin followed by nano-LC-ESI-MS/MS analysis on a high
      capacity ion trap and an LTQ Orbitrap Velos. Using two search engines, Mascot and
      ModiroTM, the recombinant 5-HT(1A) R was identified showing 94.55% sequence
      coverage. A single phosphorylation at S301 was identified and verified by
      phosphatase treatment and a series of amino acid substitutions were detected.
      Characterization of 5-HT(1A) R, a key player of brain functions and
      neurotransmission, was shown and may enable generation of specific antibodies,
      design of future, and interpretation of previous studies in the rat at the
      protein level.

PMID- 22997068
TI  - Adipogenesis using human adipose tissue-derived stromal cells combined with a
      collagen/gelatin sponge sustaining release of basic fibroblast growth factor.
AB  - We have developed a collagen/gelatin sponge (CGS) that can provide a sustained
      release of basic fibroblast growth factor (bFGF). In our previous study, it was
      shown that CGS impregnated with the appropriate dosage of bFGF accelerates dermis
      like tissue formation two or three times earlier than an existing collagen
      sponge. In this study, adipogenesis was evaluated using CGSs disseminated with
      adipose tissue-derived stem cells (ASCs). Human ASCs were primarily isolated from
      human adipose tissue that was obtained during breast cancer surgery with informed
      consent at Kyoto University Hospital. ASCs were isolated from collagenase digests
      of adipose tissue. ASCs were labelled with PKH26. CGSs (8 mm diameter * 3 mm
      thickness) were impregnated with bFGF (0.1, 1, 7, 14 ug/cm(2) ) or normal saline
      solution. Then the labelled cells were disseminated (passage 3) on CGSs at a
      seeding density of 1 * 10(5) cells/cm(2) and implanted into the back subcutis of
      nude mice. Six weeks after implantation, adipogenesis at the administered site
      was evaluated. Immunohistological staining with von Willebrand factor (vWf) was
      performed to evaluate newly formed capillaries. Newly formed adipose tissue was
      observed macroscopically and histologically in all groups. The weight and area of
      regenerated adipose tissue were largest in the 1 ug/cm(2) bFGF group. Under a
      fluorescent microscope, newly formed adipose tissue in the bFGF-administered
      group was PKH-positive. These findings show that ASCs differentiated and formed
      adipose tissue. In this study, we showed that our CGSs impregnated with bFGF
      could be used as scaffolds with ASCs for adipogenesis.

PMID- 22997069
TI  - Counteranion-directed catalysis in the Tsuji-Trost reaction: stereocontrolled
      access to 2,5-disubstituted 3-hydroxy-tetrahydrofurans.
AB  - Hydrogen bonds can play a prominent role in organometallic catalysis, as shown
      for the title reaction, in which a counteranion directs the cyclization through
      the formation of hydrogen bonds that likely involve a proton of the pi
      allyl/palladium species itself. The reaction allows access to four out of the
      eight stereoisomers of 2,5-disubstitued 3-hydroxy-tetrahydrofurans and thus
      fragments of complex natural products.

PMID- 22997070
TI  - Structure-retention relationship study of polyoxygenated steroids.
AB  - The chromatographic behavior of 31 newly synthesized polyoxygenated steroids was
      investigated by the means of reversed-phase planar chromatography. Retention data
      were correlated to molecular characteristics of the analytes with view to examine
      possible relationships by the means of multiple linear regression (MLR) and
      partial least square (PLS) regression. On the basis of comparison of the
      statistical parameters obtained for both MLR and PLS models, descriptors best
      describing the analyte behavior were selected. Statistically significant and
      physically meaningful structure-retention relationships were obtained. Calculated
      lipophilicity expressed as XlogP as well surface tension and Hansen hydrogen
      bonding was included in both MLR and PLS models.

PMID- 22997071
TI  - Performance of five FDA-approved rapid antigen tests in the detection of 2009
      H1N1 influenza A virus.
AB  - Rapid antigen tests are commonly used by clinicians for rapid, simple, point-of
      care testing. Five rapid antigen tests were shown to have low sensitivity (40.3
      58.8%) when compared to real-time RT-PCR using nasal wash specimens from patients
      with influenza-like-illness (N = 167) that were collected previously and
      confirmed as 2009 pandemic influenza A (H1N1)-positive by PCR. Rapid antigen test
      sensitivity correlated with virus levels in nasal secretions when comparisons
      were made to cycle threshold (C(T)) values obtained from real-time RT-PCR. When
      C(T) values are <25 (equating to viral concentrations of >10(4)  TCID(50)/ml)
      sensitivity for all five rapid antigen kits was high (range: 83-94% positive);
      however, when C(T) values are >30 (10(2)  TCID(50)/ml), sensitivities of only 16
      18% were observed for four of five rapid antigen kits. The Directigen EZ Flu A +
      B test detected more positive samples (35%) at lower viral concentrations with
      C(T) values >30 when compared with other commercial kits (P = 0.05). Rapid
      antigen test results must be interpreted with caution, and negative specimens may
      need confirmation by sensitive molecular assays.

PMID- 22997073
TI  - Lack of benefit of 3-month intensification with enfuvirtide plus optimized
      background regimen (OBR) versus OBR alone in patients with multiple therapeutic
      failures: the INNOVE study.
AB  - The objective of the present study was to evaluate the virological efficacy of a
      3-month short-course intensification with enfuvirtide (ENF) associated with an
      optimized background regimen (OBR) in treatment-experienced patients infected
      with HIV-1 with multiple therapeutic failures. This was a prospective,
      randomized, open-label multicenter trial including patients infected with HIV-1
      and harboring a multi-resistant virus that was still susceptible to at least 2
      active compounds. Patients were randomized (1:1) to receive OBR + ENF or OBR
      alone. ENF was discontinued at Week 12. The primary endpoint was the proportion
      of patients with plasma viral load <50 copies/ml at Week 24. Fifteen patients
      were randomized into the OBR group and 14 into the OBR + ENF group with a median
      viral load of 4.1 log(10)  copies/ml and a median CD4+ cell count of 346
      cells/mm(3) . The primary endpoint was achieved in 93% (14/15) and 79% (11/14) of
      patients, respectively. Eighty-seven percent (13/15) of patients had a viral load
      <50 copies/ml as soon as Week 12 in the OBR group and 79% (11/14) in the OBR +
      ENF group. At Week 12, the median CD4+ cell count was 327 in the OBR and 437 in
      the OBR + ENF groups and at Week 24 they were comparable. Intensification with
      ENF had no significant impact on PBMCs HIV-DNA levels. A 3-month short-course
      intensified treatment with ENF did not improve Week-24 virological response in
      treatment-experienced patients infected with HIV-1 harboring resistant viruses
      that were still susceptible to two antiretroviral drugs.

PMID- 22997074
TI  - Frequency and clinical significance of core promoter and precore region mutations
      in Tunisian patients infected chronically with hepatitis B.
AB  - Genetic variability of hepatitis B virus (HBV) in the C gene and its association
      with the different stages of chronic liver disease has been studied inadequately
      with controversial results. The objectives of the current study were to determine
      the frequency of core promoter and precore mutations in chronic hepatitis B in
      Tunisia and to evaluate their impact on viral replication and disease
      progression. Sequencing was performed in upstream regulatory sequence (URS), pre
      core (PreC) and basal core promoter (BCP) regions for 123 chronic infected
      patients by HBV genotype D at different status of disease. Mutations were
      detected in 98.4% of cases, affecting URS, BCP and Pre-C in 95.1%, 95.9% and
      87.8% respectively. Multi-mutations increased significantly from asymptomatic
      carrier to advanced liver disease status. G1896A (74.8%), G1764A/T/C (71.5%),
      G1899A (54.4%) and T1678C (52%) were the most common. Special attention should be
      paid to A1703T, T1678C/G-A1703T, and A1652G-A1679G mutations probably specific of
      Tunisians sequences; they were observed in 40.6%, 41.5% and 30.1% respectively.
      A1679G/C, T1753C/G/A, A1762T/G and A1762T-G1764A were more prevalent in older
      patients. High DNA levels were associated with G1899A or G1764T/C-C1766G-C1799G
      and advanced liver disease with mutations at positions 1762, 1764 and/or 1899
      alone or in double or triple mutations. It was also shown that substitutions at
      nucleotides 1762, 1764 and 1899 have an impact on the disease progression. It is
      the first report for specific mutations in the URS region for genotype D. It
      should be completed by studying eventual correlation with clinical progression
      and the response to treatment.

PMID- 22997075
TI  - Expression of CD81, SR-BI and LDLR in lymphocytes and monocytes from patients
      with classic and occult hepatitis C virus infection.
AB  - CD81, the scavenger receptor-BI (SR-BI) and the low-density lipoprotein receptor
      (LDLR) are involved in peripheral blood mononuclear cells (PBMCs) hepatitis C
      virus (HCV) entry. To investigate if these molecules are altered by HCV, 20
      controls and 66 patients: 37 untreated and 29 sustained virological responders,
      were studied. CD81 and LDLR expression, measured the percentage of cells
      expressing the HCV-receptors and their mean fluorescence intensity (MFI), was
      analyzed on lymphocytes and monocytes, as well as SR-BI on monocytes by flow
      cytometry. RNA was extracted from PBMCs and detection of the HCV-RNA positive and
      negative strands was performed by strand-specific RT-PCR. A statistically
      significant increase of CD81 expression was observed on lymphocytes, a higher
      percentage of LDLR on lymphocytes and monocytes, as well as SR-BI on monocytes
      was found in the patients as compared to the controls (P < 0.05 in all cases).
      Untreated patients showed a higher percentage of LDLR(+) lymphocytes than
      sustained virological responders (P = 0.025). Nineteen sustained virological
      responders bore the HCV-RNA positive strand in PBMCs; nine of them the negative
      strand too. Sustained virological responders with occult infection and viral
      replication, showed a higher expression of LDLR on lymphocytes (P < 0.05) and a
      higher LDLR MFI on monocytes (P = 0.011) than those without viral replication. In
      conclusion, HCV exposure modifies expression levels of the receptors studied,
      being LDLR related with HCV replication, not only in the classic but also in the
      occult infection.

PMID- 22997076
TI  - Gender differences in hepatitis C seroprevalence and suboptimal vaccination and
      hepatology services uptake amongst substance misusers.
AB  - Injecting drug users are the principal at risk group for blood borne viruses. The
      aim was to assess the feasibility of screening substance misusers for blood borne
      viruses, and to offer appropriate vaccinations/referral to hepatology services.
      This was a nurse led prospective 6-month study based at a large Substance Misuse
      Service in south east England. Of the 196 consecutive individuals assessed, 81
      were eligible for HBV immunization of whom only 33.3% completed a vaccination
      course. Prevalence of positive serological markers were: anti-HBc 14.4%, HBsAg
      1.5%, and HCV antibody 37.9%. Compared to men, women were more likely to accept
      blood borne virus testing (83.3% vs. 62.3%), have ever injected (89.6% vs.
      76.3%), overdose (54.2% vs. 23.6%), be anti-HBc positive (27.5% vs. 8.8%), drink
      alcohol above national recommended guidelines (41.7% vs. 25.7%), and have a
      positive HCV serology (55% vs. 30.4%) (P <= 0.05 for all). Of the 73 individuals
      identified with a positive HBsAg and or HCV antibody, only 14 (19.1%) were known
      to hepatology services and 8 (20%) of those eligible subsequently accepted a
      specialist referral. In conclusion, serological markers for blood borne viruses
      remain high in substance misusers (anti-HBc 14.4%, HCV antibody 37.9%), with
      women more likely to be positive. Overall, only 33.3% and 20%, respectively,
      complete HBV vaccination and accept a hepatology referral. A multidisciplinary
      approach is paramount to address both the blood borne viruses and the substance
      misuse and realignment of hepatitis services to Substance Misuse Services may
      offer such a strategy.

PMID- 22997072
TI  - Impact of seminal cytomegalovirus replication on HIV-1 dynamics between blood and
      semen.
AB  - The genital tract of individuals infected with human immunodeficiency virus type
      1 (HIV-1) is an anatomic compartment that supports local HIV-1 and
      cytomegalovirus (CMV) replication. This study investigated the association of
      seminal CMV replication with changes in HIV-1 clonal expansion, evolution and
      phylogenetic compartmentalization between blood and semen. Fourteen paired blood
      and semen samples were analyzed from four untreated subjects. Clonal sequences (n
      = 607) were generated from extracted HIV-1 RNA (env C2-V3 region), and HIV-1 and
      CMV levels were measured in the seminal plasma by real-time PCR. Sequence
      alignments were evaluated for: (i) viral compartmentalization between semen and
      blood samples using Slatkin-Maddison and F(ST) methods, (ii) different nucleotide
      substitution rates in semen and blood, and (iii) association between proportions
      of clonal HIV-1 sequences in each compartment and seminal CMV levels. Half of the
      semen samples had detectable CMV DNA, with at least one CMV positive sample for
      each patient. Seminal CMV DNA levels correlated positively with seminal HIV-1 RNA
      levels (Spearman P = 0.05). A trend towards an association between
      compartmentalization of HIV-1 sequences sampled from blood and semen and presence
      of seminal CMV was observed (Cochran Q test P = 0.12). Evolutionary rates between
      semen and blood HIV-1 populations did not differ significantly, and there was no
      significant association between seminal CMV DNA levels and the frequency of non
      unique clonal HIV-1 sequences in the semen. In conclusion, the effects of CMV
      replication on HIV-1 viral and immunologic dynamics within the male genital tract
      are not significant enough to perturb evolution or disrupt compartmentalization
      in the genital tract.

PMID- 22997077
TI  - Distribution of hepatitis C virus genotypes in a diverse US integrated health
      care population.
AB  - Hepatitis C virus (HCV) genotypes influence response to therapy, and recently
      approved direct-acting antivirals are genotype-specific. Genotype distribution
      information can help to guide antiviral development and elucidate infection
      patterns. HCV genotype distributions were studied in a diverse cross-section of
      patients in the Northern California Kaiser Permanente health plan. Associations
      between genotype and race/ethnicity, age, and sex were assessed with multivariate
      logistic regression models. The 10,256 patients studied were median age 56 years,
      62% male, 55% White non-Hispanic. Overall, 70% were genotype 1, 16% genotype 2,
      12% genotype 3, 1% genotype 4, <1% genotype 5, and 1% genotype 6. Blacks (OR 4.5
      [3.8-5.5]) and Asians (OR 1.2 [1.0-1.4]) were more likely to have genotype 1 than
      2/3 versus non-Hispanic Whites. Women less likely had genotype 1 versus 2/3 than
      did men (OR 0.86 [0.78-0.94]). Versus non-Hispanic Whites, Asians (OR 0.38 [0.31
      0.46]) and Blacks (OR 0.73 [0.63-0.84]) were less likely genotype1a than 1b;
      Hispanics (OR 1.3 [1.1-1.5]) and Native Americans (OR 1.9 [1.2-2.8]) more likely
      had genotype 1a than 1b. Patients age >=65 years less likely had genotype 1a than
      1b versus those age 45-64 (OR 0.34 [0.29-0.41]). The predominance of genotype 1
      among all groups studied reinforces the need for new therapies targeting this
      genotype. Racial/ethnic variations in HCV genotype and subtype distribution must
      be considered in formulating new agents and novel strategies to successfully
      treat the diversity of hepatitis C patients.

PMID- 22997078
TI  - Diversity of human astrovirus genotypes circulating in children with acute
      gastroenteritis in Thailand during 2000-2011.
AB  - Human astrovirus (HAstV) is one of the causative agents of acute gastroenteritis
      in children worldwide. The objective of this study was to elucidate the molecular
      epidemiology and genotypic diversity of HAstV circulating in pediatric patients
      admitted to hospital with diarrhea in Thailand during the year 2000-2011, except
      for 2004, 2006, and 2009. A total of 1,022 fecal specimens were tested for HAstV
      by reverse transcription polymerase chain reaction (RT-PCR). HAstV was detected
      at 1.4% (14 of 1,022). All HAstV strains detected in this study were
      characterized further by nucleotide sequencing and phylogenetic analysis.
      Analysis of 348 bp partial capsid nucleotide sequences revealed that HAstV
      strains detected were HAstV-1 (1a, 1b, and 1d) (8 strains), HAstV-2 (2c) (3
      strains), HAstV-3 (1 strain), and HAstV-5 (2 strains). HAstV-1, the most
      predominant genotype was detected initially in 2002 and circulated continuously
      up to 2011. HAstV-2 was detected in year 2001, and 2007 and grouped into a 2c
      lineage. HAstV-3 was found only in 2000 and HAstV-5 was found in the year 2001.
      The findings indicate that a wide variety of HAstV strains continue to circulate
      in children admitted to hospital with acute gastroenteritis in Thailand over a
      decade. The data provide an epidemiological overview of HAstV infection and HAstV
      genotype distribution in Thailand.

PMID- 22997079
TI  - Identification of prohibitin as a Chikungunya virus receptor protein.
AB  - Chikungunya virus (CHIKV) has recently re-emerged causing millions of infections
      in countries around the Indian Ocean. While CHIKV has a broad host cell range and
      productively infects a number of different cell types, macrophages have been
      identified as a potential viral reservoir serving to increase the duration of
      symptoms. To date no CHIKV interacting protein has been characterized and this
      study sought to identify CHIKV binding proteins expressed on target cell
      membranes. Two-dimensional virus overlay identified prohibitin (PHB) as a
      microglial cell expressed CHIKV binding protein. Co-localization, co
      immunoprecipitation as well as antibody and siRNA mediated infection inhibition
      studies all confirmed a role for PHB in mediating internalization of CHIKV into
      microglial cells. PHB is the first identified CHIKV receptor protein, and this
      study is evidence that PHB may play a role in the internalization of multiple
      viruses.

PMID- 22997080
TI  - Utility of IgM ELISA, TaqMan real-time PCR, reverse transcription PCR, and RT
      LAMP assay for the diagnosis of Chikungunya fever.
AB  - Chikungunya fever a re-emerging infection with expanding geographical boundaries,
      can mimic symptoms of other infections like dengue, malaria which makes the
      definitive diagnosis of the infection important. The present study compares the
      utility of four laboratory diagnostic methods viz. IgM capture ELISA, an in house
      reverse transcription PCR for the diagnosis of Chikungunya fever, TaqMan real
      time PCR, and a one step reverse transcription-loop mediated isothermal
      amplification assay (RT-LAMP). Out of the 70 serum samples tested, 29 (41%) were
      positive for Chikungunya IgM antibody by ELISA and 50 (71%) samples were positive
      by one of the three molecular assays. CHIKV specific nucleic acid was detected in
      33/70 (47%) by reverse transcription PCR, 46/70 (66%) by TaqMan real-time PCR,
      and 43/70 (62%) by RT-LAMP assay. A majority of the samples (62/70; 89%) were
      positive by at least one of the four assays used in the study. The molecular
      assays were more sensitive for diagnosis in the early stages of illness (2-5 days
      post onset) when antibodies were not detectable. In the later stages of illness,
      the IgM ELISA is a more sensitive diagnostic test. In conclusion we recommend
      that the IgM ELISA be used as an initial screening test followed one of the
      molecular assays in samples that are collected in the early phase of illness and
      negative for CHIKV IgM antibodies. Such as approach would enable rapid
      confirmation of the diagnosis and implementation of public health measures
      especially during outbreaks.

PMID- 22997081
TI  - Enterovirus 71 blocks selectively type I interferon production through the 3C
      viral protein in mice.
AB  - Type I interferons (IFNs) represent an essential innate defense mechanism for
      controlling enterovirus 71 (EV 71) infection. Mice inoculated with EV 71 produced
      a significantly lower amount of type I IFNs than those inoculated with poly
      (I:C), adenovirus type V, or coxsackievirus B3 (CB3). EV 71 infection, however,
      mounted a proinflammatory response with a significant increase in the levels of
      serum and brain interleukin (IL)-6, monocyte chemoattractant protein-1, tumor
      necrosis factor, and IFN-gamma. EV 71 infection abolished both poly (I:C)- and
      CB3-induced type I IFN production of mice. Such effect was not extended to other
      enteroviruses including coxsackievirus A24, B2, B3, and echovirus 9, as mice
      infected with these viruses retained type I IFN responsiveness upon poly (I:C)
      challenge. In addition, EV 71-infected RAW264.7 cells produced significantly
      lower amount of type I IFNs than non-infected cells upon poly (I:C) stimulation.
      The inhibitory effect of EV 71 on type I IFN production was attributed to the
      viral protein 3C, which was confirmed using over-expression systems in both mice
      and RAW264.7 cells. The 3C over-expression, however, did not interfere with poly
      (I:C)-induced proinflammatory cytokine production. These findings indicate that
      EV 71 can hamper the host innate defense by blocking selectively type I IFN
      synthesis through the 3C viral protein.

PMID- 22997082
TI  - Can hantavirus infections be predicted on admission to hospital?
AB  - The aim of this study was to investigate the predictive factors which contribute
      to diagnosis of hantavirus infection. One hundred patients from rural areas
      hospitalized with a preliminary diagnosis of hantavirus infection from different
      hospitals in Turkey were investigated. Hantavirus infection was confirmed in 20
      patients (Group 1) using immunofluorescence and immunoblot assays at the Refik
      Saydam National Public Health Agency. Hantaviruses were not detected in the serum
      of the remaining 80 patients, other infectious and non-infectious diseases being
      diagnosed in this group (Group 2). Patients' demographic characteristics and
      clinical and laboratory data on admission were examined and compared between the
      two groups. Fever, proteinuria, hematuria, lethargy-weakness, and nausea-vomiting
      were the most frequent symptoms and findings in Group 1, seen in almost all
      patients. Proteinuria, hematuria, muscle pain, diarrhea/abdominal pain,
      hypotension, shock, and sweating were observed at significantly higher levels in
      Group 1 compared to Group 2. Serum urea, creatinine, uric acid, lactate
      dehydrogenase (LDH), aspartate transaminase (AST), alkaline phosphatase (ALP),
      and C-reactive protein (CRP) were significantly higher, but serum platelet counts
      were lower in Group 1 patients. Area beneath the receiver operating
      characteristics (ROC) curve analysis was used to calculate the discriminative
      ability of various laboratory values to identify patients with hantavirus
      infection. This analysis revealed that, serum CRP had a 100% negative predictive
      value, whilst, platelet, and creatinine had 75% and 70% positive predictive
      values for the diagnosis of hantavirus infection. In summary, laboratory markers
      used in clinical practice are of great importance predicting hantavirus
      infections.

PMID- 22997083
TI  - Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus
      and age.
AB  - Recent studies have shown that cytomegalovirus (CMV) may be an emerging marker of
      immunosenescence. CMV can affect the immune system by directly infecting
      leukocytes and hematopoietic cells or by eliciting an expansion of oligoclonal
      CD8+ T cells/contraction of the naive T cell compartment that may reduce the
      host's ability to fight other pathogens. To investigate further CMV-associated
      changes in immunity, a study was conducted with 1,454 adults (ages 25-91) to
      determine the association between CMV and reactivation of another latent
      herpesvirus, Herpes simplex virus type 1 (HSV-1), as indexed by antibody titers.
      Elevated antibody titers to latent HSV-1 were significantly associated with both
      CMV seropositivity and high CMV antibody levels. Evaluation by specific age
      groups (<45, 45-64, and 65+ years old) revealed that this association was
      detectable early in life (<45 years of age). Increases in HSV-1 antibodies by age
      occurred in CMV seropositive individuals but not CMV seronegative subjects.
      Within CMV seropositive subjects, increases in HSV-1 antibodies by age were only
      found in individuals with low CMV antibody levels as those with high CMV
      antibodies already exhibited elevated HSV-1 antibodies. These associations
      remained significant after accounting for body mass index, gender, and
      socioeconomic status. These results suggest that CMV can influence the immune
      response to another pathogen and support the concept that CMV may accelerate
      immunosenescence.

PMID- 22997084
TI  - Diagnosis of hand, foot, and mouth disease caused by EV71 and other enteroviruses
      by a one-step, single tube, duplex RT-PCR.
AB  - Hand, foot, and mouth disease (HFMD) is caused mainly by enterovirus 71 (EV71)
      and other enteroviruses (EVs) such as Coxsackie A16 in China. EV71 infection can
      lead to severe clinical manifestations and even death. Other EVs, however,
      generally cause mild symptoms. Thus, early and accurate distinction of EV71 from
      other EVs for HFMD will offer significant benefits. A one-step, single tube,
      duplex RT-PCR assay is described in the present study to detect simultaneously
      EV71 and other EVs. The primers used for the duplex RT-PCR underwent screening
      and optimization. The detection threshold was 0.001 TCID(50)/ml for EV71 and 0.01
      TCID(50)/ml for other EVs. The positive rate of enterovirus detection in 165
      clinical samples reached 68.5%, including 46.1% for EV71 and 22.4% for other EVs.
      Of all the severe HFMD cases, EV71 was responsible for 85.3% cases. The positive
      rate of EV71 fell markedly by day 8 after onset. In addition, sequencing of EV71
      specific amplicons from duplex RT-PCR revealed that C4a was the predominant
      subgenotype of EV71 circulating in Nanjing, China. The accuracy and reliability
      of the assay suggest strongly that the one-step, single tube, duplex RT-PCR will
      be useful for early diagnosis and monitoring of EV71 and other EV infections.

PMID- 22997085
TI  - Immunological and viral features in patients with overactive bladder associated
      with human T-cell lymphotropic virus type 1 infection.
AB  - The majority of patients infected with human T-cell lymphotropic virus-type 1
      (HTLV-1) are considered carriers, but a high frequency of urinary symptoms of
      overactive bladder, common in HTLV-1 associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) have been documented in these patients. The aim of this
      study was to determine if immunological and viral factors that are seen in
      HAM/TSP are also observed in these patients. Participants were classified as HTLV
      1 carriers (n = 45), HTLV-1 patients suffering from overactive bladder (n = 45)
      and HAM/TSP (n = 45). Cells from HTLV-1 overactive bladder patients produced
      spontaneously more proinflammatory cytokines than carriers. TNF-alpha and IL-17
      levels were similar in HAM/TSP and HTLV-1 overactive bladder patients. High
      proviral load was found in patients with overactive bladder and HAM/TSP and
      correlated with proinflammatory cytokines. In contrast with findings in patients
      with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV-1 overactive
      bladder and carriers. Exogenous addition of regulatory cytokines decreased
      spontaneous IFN-gamma production in cell cultures from HTLV-1 overactive bladder
      patients. The results show that HTLV-1 overactive bladder and HAM/TSP patients
      have in common some immunological features as well as similar proviral load
      profile. The data show that HTLV-1 overactive bladder patients are still able to
      down regulate their inflammatory immune response. In addition, these patients
      express levels of chemokines similar to carriers, which may explain why they have
      yet to develop the same degree of spinal cord damage as seen in patients with
      HAM/TSP. These patients present symptoms of overactive bladder, which may be an
      early sign of HAM/TSP.

PMID- 22997086
TI  - Distribution of JC polyomavirus genotypes in Tunisian renal transplant recipients
      between January 2008 and January 2011.
AB  - The polyomavirus JC (JCPyV) is a ubiquitous virus in humans, causing progressive
      multifocal leukoencephalopathy, a fatal demyelinating disease. JCPyV propagates
      in the adult kidney and excretes its progeny in urine, from which its DNA can be
      recovered readily. JCPyV isolates worldwide can be classified into 14 subtypes or
      genotypes, each associated with a specific geographical region. The European
      genotypes EU-a-b-c are spread throughout Europe and Mediterranean areas. The
      major African genotype Af2 is spread not only throughout Africa but also in West
      and South Asia. A minor African genotype (Af1) occurs in Central and West Africa.
      Partially overlapping domains in Asia were occupied by various genotypes (e.g.,
      B1-a, -b, -d, B2, CY, MY, and SC). To characterize the subtypes of JCPyV
      prevalent in Tunisia, the presence of the virus was investigated by real-time PCR
      in urine samples from 98 renal transplant recipients. For subtype identification,
      a 610 bp typing region of the JCPyV genome was amplified from each urine sample,
      and its DNA sequence was determined. In the patients studied, the major African
      subtype Af2 was the predominant (62.5%), followed by the European subtype EU
      (33.5%). Only one case clustering with the Asian genotype SC (4%) was identified.
      The presence of the European subtype with high prevalence in this population
      suggests that the epidemiological distribution of JCPyV virus sequences in North
      Africa is related partially to the epidemiological data in Europe.

PMID- 22997087
TI  - Shift in the timing of respiratory syncytial virus circulation in a subtropical
      megalopolis: implications for immunoprophylaxis.
AB  - Respiratory syncytial virus (RSV) is the most common cause of severe respiratory
      infections worldwide, and an important cause of childhood bronchiolitis,
      pneumonia, and mortality. Although prevention of RSV infection by
      immunoprophylaxis with palivizumab has proved effective, a precise understanding
      of the timing of RSV outbreaks is necessary to ensure that infants are protected
      when RSV is circulating. In this study a consistent shift in the seasonal
      patterns of RSV circulation in southeast Brazil (Sao Paulo) is reported based on
      the analysis of 15 years of viral surveillance. Surveillance was conducted from
      1996 to 2010 and involved the collection of samples from children with symptoms
      of acute respiratory infection. Putative changes in school terms, in the
      proportion of RSV genotypes infecting children and in the seasonal dynamics of
      several climatic parameters during the period were also investigated. The results
      revealed a progression in the timing of RSV seasons, with a shift in the onset
      and peak of RSV epidemics from 2007 onwards. Although lower rainfall and
      temperatures were associated with the onset of outbreaks, there was no evidence
      of changes in climate, school terms or in the relative proportion of genotypes in
      the period analyzed. These findings have direct implications for improving the
      prophylactic use of palivizumab, and stress the importance of fine tuning
      prophylaxis with recent surveillance data. In the case of Sao Paulo, palivizumab
      prophylaxis should be initiated earlier than suggested currently. Similar
      adjustments may be necessary in other regions.

PMID- 22997088
TI  - Epidemiological and molecular characterization of rubella virus isolated in Sao
      Paulo, Brazil during 1997-2004.
AB  - Rubella virus (RV) infection during the early stages of pregnancy can lead to
      serious birth defects, known as the congenital rubella syndrome (CRS). In 2003,
      the Pan American Health Organization (PAHO) adopted a resolution calling for the
      elimination of rubella and the congenital rubella syndrome (CRS) in the Americas
      by the year 2010. Brazil will have implemented the recommended PAHO strategy for
      elimination and interruption of endemic rubella virus transmission. The
      characterization of genotypes during the final stages of rubella elimination is
      important for determining whether new rubella isolates represent endemic
      transmission or importations. Samples (blood, urine, cerebrospinal fluid, and
      throat swabs) collected from patients with symptoms suggestive of rubella
      infection in 1997-2004 were isolated in cell culture and genotyped. Twenty-eight
      sequences were analyzed and two genotypes were identified: 1a and 1G. The
      information reported in this paper will contribute to understanding the molecular
      epidemiology of RV in Sao Paulo, Brazil.

PMID- 22997089
TI  - A retrospective study of mortality in varanid lizards (Reptilia: Squamata:
      Varanidae) at the Bronx Zoo: implications for husbandry and reproductive
      management in zoos.
AB  - Varanid lizards have been maintained in zoological parks for more than a century,
      yet few studies to date have attempted to pinpoint significant health issues
      affecting their management or areas of captive husbandry that are in need of
      improvement. In an effort to identify and better understand some of the husbandry
      related challenges and health issues specifically affecting varanids in zoos,
      this study examined mortality in 16 species maintained at the Bronx Zoo between
      1968 and 2009. Out of 108 records reviewed, complete necropsy reports were
      available for 85 individuals. Infection-related processes including bacterial
      (15.3%), protozoal (12.9%), nematode (9.4%), and fungal (3.5%) infections
      accounted for the greatest number of deaths (47.1%). Noninfectious diseases
      including female reproductive disorders (7.1%), neoplasia (7.1%), gout (10.8%),
      and hemipenal prolapse (1.3%) accounted for 29.4% of deaths. Multiple disease
      agents were responsible for 5.9% of deaths, and a cause for death could not be
      determined for 17.7% of individuals. Reproductive complications accounted for
      11.5% of female deaths, but were identified in 23.1% of females. Although not
      necessarily the cause for death, gout was present in 18.8% of individuals.
      Differences in mortality between species, genders, and origin (captive-bred vs.
      wild-caught) were also evaluated. The results of this study corroborate earlier
      findings that identify bacterial infections, neoplasia, female reproductive
      disorders, gout, and endoparasitism as major sources of mortality in captive
      varanids. In light of these results, we discuss potential etiologies and offer
      recommendations for improving captive management practices in zoos.

PMID- 22997090
TI  - Wear of a dental composite in an artificial oral environment: A clinical
      correlation.
AB  - The study objective was to correlate wear between an in vitro method for
      simulating wear and in vivo wear of a posterior dental composite. Ten subjects
      (12 restorations) were selected from a five-year clinical study (University of
      North Carolina, School of Dentistry) that assessed wear of SureFil composite
      (Caulk, Dentsply). Subject casts were digitized and changes in volume and mean
      depth with time were calculated from the 3D digital models for contact and
      contact-free wear. SureFil composite disks were mounted in the University of
      Minnesota's Artificial Oral Environment, opposed by natural enamel, subjected to
      mandibular-like movements for 150 K, 300 K, 600 K, 1.2 M, and 1.5 M cycles, and
      loaded with peak forces of 13 N (n = 7) or 30 N (n = 3). Wear rates were
      calculated as the slope of the linear regressions fitting the wear data. Data
      were analyzed using one-way ANOVAs and post hoc t-tests where appropriate (p =
      0.05). Clinical restorations included contact wear on seven restorations and
      contact-free wear on all restorations. Contact-free wear was less than contact
      wear (p < 0.01). SureFil clinical wear rates were 0.012 mm/year (mean depth) and
      0.023 mm(3)/year (volume). Clinical restorations expanded slightly during the
      first year. Using a conversion rate of one year equals 3 * 10(5) cycles, there
      were no significant differences between the clinical and simulated data except
      depths at Year 5 and 13 N volume at Year 4. The 30 N simulation reproduced the
      clinical data if contact-free wear was taken into account. Good agreement between
      simulated and clinical wear implies that in vitro simulation can screen new
      composite formulations.

PMID- 22997091
TI  - Oncogenic PIK3CA mutations in lobular breast cancer progression.
AB  - Infiltrating lobular breast cancer (ILBC) is a tumor-biologically distinct breast
      cancer subtype. A high frequency of oncogenic PIK3CA mutations has been reported
      in ILBC, which may allow for targeted therapy with newly developed PI3K
      inhibitors. This is of particular clinical relevance for ILBC patients, who have
      failed to respond to current treatment regimes and suffer from tumor recurrence
      or dissemination. In anticipation of this therapeutic strategy, we investigated
      PIK3CA mutations in ILBC with special reference to late stage tumor progression.
      A total of 88 ILBCs from 73 patients, including primary tumors (PTs, n = 43),
      ipsilateral locally recurrent tumors (LRTs, n = 15), and distant organ metastases
      (DOMs, n = 30), were compiled on tissue microarrays. Established ILBC marker
      proteins were evaluated by immunohistochemistry and PIK3CA hot spot mutations in
      exons 9 and 20 by direct sequencing. Matched PT/LRT, PT/DOM, and DOM/DOM cases
      were characterized on a patient-by-patient basis. Following correction for
      redundant patient representations, mutation frequencies were compared in PTs
      versus LRTs or DOMs. Nearly all specimens were E-cadherin-negative (99%),
      estrogen receptor (ER)-positive (91%), and lacked basal epithelial markers
      (100%), demonstrating correct ILBC classification. PIK3CA mutations were detected
      in 32/88 (36%) specimens. The mutation rate was similar in PTs (33%) and DOMs
      (26%, P = 0.769), but approximately two-fold increased in LRTs (69%, P = 0.022).
      Consistently, matched PT/LRT and LRT/DOM cases showed additional PIK3CA mutations
      in LRTs. Intriguingly, these findings imply that PIK3CA mutations are positively
      selected for during ILBC progression to local recurrence but not distant
      metastasis, which may have clinical implications for PI3K inhibitor-based
      therapy.

PMID- 22997094
TI  - Identification of soybean proteins from a single cell type: the root hair.
AB  - Root hairs (RH) are a terminally differentiated single cell type, mainly involved
      in water and nutrient uptake from the soil. The soybean RH cell represents an
      excellent model for the study of single cell systems biology. In this study, we
      identified 5702 proteins, with at least two peptides, from soybean RH using an
      accurate mass and time tag approach, establishing a comprehensive proteome
      reference map of this single cell type. We also showed that trypsin is the most
      appropriate enzyme for soybean proteomic studies by performing an in silico
      digestion of the soybean proteome using different proteases. Although the
      majority of proteins identified in this study are involved in basal metabolism,
      the function of others are more related to RH formation/function and include
      proteins involved in nutrient uptake (transporters) or vesicular trafficking
      (cytoskeleton and ras-associated binding proteins). Interestingly, some of these
      proteins appear to be specifically detected in RH and constitute promising
      candidates for further studies to elucidate unique features of this single-cell
      model.

PMID- 22997095
TI  - A nonmetal approach to alpha-heterofunctionalized carbonyl derivatives by formal
      reductive X-H insertion.
AB  - Keeping it organic: A direct synthesis of alpha-alkoxy and alpha-amino ester
      derivatives by direct reductive coupling of widely available, stable alpha-keto
      esters and protic pronucleophiles is described (see scheme; X = OR, NR(2)). The
      method serves as a convenient nonmetal alternative to X-H insertion by diazo
      decomposition.

PMID- 22997096
TI  - Simultaneous determination of six toxic alkaloids in human plasma and urine using
      capillary zone electrophoresis coupled to time-of-flight mass spectrometry.
AB  - A novel capillary zone electrophoresis separation coupled to electro spray
      ionization time-of-flight mass spectrometry method was developed for the
      simultaneous analysis of six toxic alkaloids: brucine, strychnine, atropine
      sulfate, anisodamine hydrobromide, scopolamine hydrobromide and anisodine
      hydrobromide in human plasma and urine. To obtain optimal sensitivity, a solid
      phase extraction method using Oasis MCX cartridges (1 mL, 30 mg; Waters, USA) for
      the pretreatment of samples was used. All compounds were separated by capillary
      zone electrophoresis at 25 kV within 12 min in an uncoated fused-silica capillary
      of 75 MUm id * 100 cm and were detected by time-of-flight mass spectrometry. This
      method was validated with regard to precision, accuracy, sensitivity, linear
      range, limit of detection (LOD), and limit of quantification (LOQ). In the plasma
      and urine samples, the linear calibration curves were obtained over the range of
      0.50-100 ng/mL. The LOD and LOQ were 0.2-0.5 ng/mL and 0.5-1.0 ng/mL,
      respectively. The intra- and interday precision was better than 12% and 13%,
      respectively. Electrophoretic peaks could be identified by mass analysis.

PMID- 22997097
TI  - In vivo oxidation in retrieved highly crosslinked tibial inserts.
AB  - The current study determined (I) the environment where oxidation in a series of
      retrieved, HXL UHMWPE tibial inserts occurred (in vivo or postexplant); and (II)
      the effect of fabrication variables (irradiation source, irradiation dose) and
      thermal processing after irradiation (annealing or remelting) on oxidation
      resistance. Hypotheses examined are (1) HXL UHMWPE tibial inserts have potential
      to oxidize in vivo, and (2) annealed HXL UHMWPE oxidizes at a higher rate in vivo
      than remelted HXL UHMWPE. Highly crosslinked UHMWPE tibial inserts (87), received
      by an IRB-approved retrieval laboratory from 20 surgeons at 10 institutions
      across the U.S., were analyzed from 2005 to 2011. Fourier transform infrared
      spectroscopy was used to determine oxidation and trans-vinylene index for each
      retrieved insert. Measured oxidation that was maximum subsurface was found in 56%
      of all HXL tibial inserts. This maximum oxidation correlated significantly with
      in vivo time, trans-vinylene index, and thermal processing after irradiation.
      Articular oxidation rate correlated with crosslinking irradiation dose and
      thermal processing after irradiation. Retrieved below-melt annealed tibial
      inserts had significantly higher articular oxidation rates than remelted tibial
      inserts (p < 0.001). Articular oxidation rates correlated positively with cross
      linking irradiation dose and postirradiation thermal processing. Edge oxidation
      correlated with postirradiation thermal processing. Oxidation of HXL UHMWPE may
      have clinical implications for tibial inserts, since loss of UHMWPE toughness
      resulting from oxidation has led to fatigue damage in gamma-sterilized tibial
      inserts.

PMID- 22997099
TI  - A thermally stable gold(III) hydride: synthesis, reactivity, and reductive
      condensation as a route to gold(II) complexes.
AB  - Going for gold: The first thermally stable gold(III) hydride [(C N C)*AuH] is
      presented. It undergoes regioselective insertions with allenes to give gold(III)
      vinyl complexes, and reductive condensation with [(C N C)*AuOH] to the air-stable
      Au(II) product, [(C N C)*(2)Au(2)], with a short nonbridged gold-gold bond.

PMID- 22997098
TI  - Proteomic features of potential tumor suppressor NESG1 in nasopharyngeal
      carcinoma.
AB  - We previously defined the recently revised NESG1 gene as a potential tumor
      suppressor in nasopharyngeal carcinoma (NPC). Here, we further used proteomics
      technology to globally examine NESG1-controlled proteins in NPC cells. Twenty-six
      proteins were found to be deregulated by NESG1 using proteomics analysis while
      enolase 1 (alpha) (ENO1), heat shock protein 90 kDa beta (Grp94), member 1
      (HSP90B1), and cathepsin D (CTSD) proteins were differentially expressed by
      Western blot. Interestingly, a-enolase (ENO1), an overexpressed gene in NPC, was
      confirmed as a NESG1-regulated protein in NPC cells. Overexpressed ENO1 not only
      restored cell proliferation and cell-cycle progression, but also antagonized the
      regulation of NESG1 to cell-cycle regulators p21 and CCNA1 expression as well as
      induced the expression of C-Myc, pRB, and E2F1 in NESG1-ovexpressed NPC cells.
      Real-time PCR and immunohistochemistry analysis showed that NESG1 expression is
      negatively correlated with ENO1 expression in NPC tissues. Our observations
      suggest that ENO1 downregulation plays an important role in NESG1-induced growth
      inhibition of NPC cancer cells.

PMID- 22997100
TI  - Predicting retention in reverse-phase liquid chromatography at different mobile
      phase compositions and temperatures by using the solvation parameter model.
AB  - The prediction capability of the solvation parameter model in reverse-phase
      liquid chromatography at different methanol-water mobile phase compositions and
      temperatures was investigated. By using a carefully selected set of solutes, the
      training set, linear relationships were established through regression equations
      between the logarithm of the solute retention factor, logk, and different solute
      parameters. The coefficients obtained in the regressions were used to create a
      general retention model able to predict retention in an octadecylsilica
      stationary phase at any temperature and methanol-water composition. The validity
      of the model was evaluated by using a different set (the test set) of 30 solutes
      of very diverse chemical nature. Predictions of logk values were obtained at two
      different combinations of temperature and mobile phase composition by using two
      different procedures: (i) by calculating the coefficients through a mathematical
      linear relationship in which the mobile phase composition and temperature are
      involved; (ii) by using a general equation, obtained by considering the previous
      results, in which only the experimental values of temperature and mobile phase
      composition are required. Predicted logk values were critically compared with the
      experimental values. Excellent results were obtained considering the diversity of
      the test set.

PMID- 22997101
TI  - Molecular characterisation of gastrointestinal microbiota of children with autism
      (with and without gastrointestinal dysfunction) and their neurotypical siblings.
AB  - Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal
      problems such as diarrhoea, constipation and abdominal pain. This has stimulated
      investigations into possible abnormalities of intestinal microbiota in autistic
      patients. Therefore, we designed this study to identify differences (and/or
      similarities) in the microbiota of children with autism (without gastrointestinal
      dysfunction: n = 23; with gastrointestinal dysfunction: n = 28) and their
      neurotypical siblings (n = 53) who share a similar environment using bacterial
      tag-encoded FLX amplicon pyrosequencing. Regardless of the diagnosis and
      sociodemographic characteristics, overall, Firmicutes (70%), Bacteroidetes (20%)
      and Proteobacteria (4%) were the most dominant phyla in samples. Results did not
      indicate clinically meaningful differences between groups. The data do not
      support the hypothesis that the gastrointestinal microbiota of children with ASD
      plays a role in the symptomatology of ASD. Other explanations for the
      gastrointestinal dysfunction in this population should be considered including
      elevated anxiety and self-restricted diets.

PMID- 22997102
TI  - Introduction of a high-throughput double-stent animal model for the evaluation of
      biodegradable vascular stents.
AB  - Current stent system efficacy for the treatment of coronary artery disease is
      hampered by in-stent restenosis (ISR) rates of up to 20% in certain high-risk
      settings and by the risk of stent thrombosis, which is characterized by a high
      mortality rate. In theory, biodegradable vascular devices exhibit crucial
      advantages. Most absorbable implant materials are based on poly-L-lactic acid
      (PLLA) owing to its mechanical properties; however, PLLA might induce an
      inflammatory reaction in the vessel wall. Evaluation of biodegradable implant
      efficacy includes a long-term examination of tissue response; therefore, a simple
      in vivo tool for thorough biocompatibility and biodegradation evaluation would
      facilitate future stent system development. Rats have been used for the study of
      in vivo degradation processes, and stent implantation into the abdominal aorta of
      rats is a proven model for stent evaluation. Here, we report the transformation
      of the porcine double-stent animal model into the high-throughput rat abdominal
      aorta model. As genetic manipulation of rats was introduced recently, this novel
      method presents a powerful tool for future in vivo biodegradable candidate stent
      biocompatibility and biodegradation characterization in a reliable simple model
      of coronary ISR.

PMID- 22997105
TI  - Efficacy of methylprednisolone in children with severe community acquired
      pneumonia.

PMID- 22997103
TI  - Validation of a robust proteomic analysis carried out on formalin-fixed paraffin
      embedded tissues of the pancreas obtained from mouse and human.
AB  - A number of reports have recently emerged with focus on extraction of proteins
      from formalin-fixed paraffin-embedded (FFPE) tissues for MS analysis; however,
      reproducibility and robustness as compared to flash frozen controls is generally
      overlooked. The goal of this study was to identify and validate a practical and
      highly robust approach for the proteomics analysis of FFPE tissues. FFPE and
      matched frozen pancreatic tissues obtained from mice (n = 8) were analyzed using
      1D-nanoLC-MS(MS)(2)  following work up with commercially available kits. The
      chosen approach for FFPE tissues was found to be highly comparable to that of
      frozen. In addition, the total number of unique peptides identified between the
      two groups was highly similar, with 958 identified for FFPE and 1070 identified
      for frozen, with protein identifications that corresponded by approximately 80%.
      This approach was then applied to archived human FFPE pancreatic cancer specimens
      (n = 11) as compared to uninvolved tissues (n = 8), where 47 potential pancreatic
      ductal adenocarcinoma markers were identified as significantly increased, of
      which 28 were previously reported. Further, these proteins share strongly
      overlapping pathway associations to pancreatic cancer that include estrogen
      receptor alpha. Together, these data support the validation of an approach for
      the proteomic analysis of FFPE tissues that is straightforward and highly robust,
      which can also be effectively applied toward translational studies of disease.

PMID- 22997106
TI  - Quantitative in vitro assessment of Mg65 Zn30 Ca5 degradation and its effect on
      cell viability.
AB  - A bulk metallic glass (BMG) of composition Mg(65) Zn(30) Ca(5) was cast directly
      from the melt and explored as a potential bioresorbable metallic material. The in
      vitro degradation behavior of the amorphous alloy and its associated effects on
      cellular activities were assessed against pure crystalline magnesium.
      Biocorrosion tests using potentiodynamic polarization showed that the amorphous
      alloy corroded at a much slower rate than the crystalline Mg. Analysis of the
      exchanged media using inductively coupled plasma optical emission spectrometry
      revealed that the dissolution rate of Mg ions in the BMG was 446 MUg/cm(2)/day,
      approximately half the rate of crystalline Mg (859 MUg/cm(2)/day). A cytotoxicity
      study, using L929 murine fibroblasts, revealed that both the BMG and pure Mg are
      capable of supporting cellular activities. However, direct contact with the
      samples created regions of minimal cell growth around both amorphous and
      crystalline samples, and no cell attachment was observed.

PMID- 22997107
TI  - Affinity capillary electrophoresis method for investigation of bile salts
      complexation with sulfobutyl ether-beta-cyclodextrin.
AB  - Sulfobutyl ether-beta-cyclodextrin (SBEbetaCD) is utilized in preformulation and
      drug formulation as an excipient for solubilization of drugs with poor aqueous
      solubility. Approximately seven negative charges of SBEbetaCD play a role with
      respect to solubilization and complexation, but also have an influence on the
      ionic strength of the background electrolyte when the cyclodextrin is used in
      capillary electrophoresis. Mobility-shift affinity capillary methods for
      investigation of the complexation of taurocholate and taurochenodeoxycholate with
      the negatively charged cyclodextrin derivative applying constant power and ionic
      strength conditions as well as constant voltage and varying ionic strength were
      investigated. A new approach for the correction of background electrolyte ionic
      strength was developed. Mobility-shift affinity capillary electrophoresis
      experiments obtained at constant voltage and constant power settings were
      compared and found to provide binding parameters that were in good agreement upon
      correction. The complexation of taurochenodeoxycholate with SBEbetaCD was
      significantly stronger than the corresponding interaction involving taurocholate.
      The obtained stability constants for the bile salts were in the same range as
      those previously reported for the interaction with neutral beta-cyclodextrins
      derivatives, i.e. the positions of the negative charges on SBEbetaCD and the bile
      salts within the complex did not lead to significant electrostatic repulsion.

PMID- 22997108
TI  - FDA approves four-drug anti-HIV combination tablet.

PMID- 22997109
TI  - Few therapy options available for carbapenem-resistant Klebsiella.

PMID- 22997110
TI  - CMS to compensate hospitals for inpatient use of fidaxomicin, glucarpidase.

PMID- 22997111
TI  - New term will distinguish tablets known to split in half.

PMID- 22997112
TI  - Assessment of metoprolol tartrate dosage in the outpatient setting.

PMID- 22997113
TI  - FDA recognition of first-world drug regulators as means of relieving U.S. drug
      shortages.

PMID- 22997114
TI  - Smart pump use in pediatric patients.

PMID- 22997115
TI  - Establishing a telemedicine clinic for HIV patients in a correctional facility.

PMID- 22997116
TI  - Colloids in the intensive care unit.
AB  - PURPOSE: The most recent published evidence on the use of colloids versus
      crystalloids in critical care is reviewed, with a focus on population-dependent
      differences in safety and efficacy. SUMMARY: Colloids offer a number of
      theoretical advantages over crystalloids for fluid resuscitation, but some
      colloids (e.g., hydroxyethyl starch solutions, dextrans) can have serious adverse
      effects, and albumin products entail higher costs. The results of the influential
      Saline Versus Albumin Fluid Evaluation (SAFE) trial and a subsequent SAFE
      subgroup analysis indicated that colloid therapy should not be used in patients
      with traumatic brain injury and other forms of trauma due to an increased
      mortality risk relative to crystalloid therapy. With regard to patients with
      severe sepsis, two meta-analyses published in 2011, which collectively evaluated
      82 trials involving nearly 10,000 patients, indicated comparable outcomes with
      the use of either crystalloids or albumins. For patients requiring extracorporeal
      cardiopulmonary bypass (CPB) during heart surgery, the available evidence
      supports the use of a colloid, particularly albumin, for CPB circuit priming and
      postoperative volume expansion. In select patients with burn injury, the
      published evidence supports the use of supplemental colloids if adequate urine
      output cannot be maintained with a crystalloid-only rescue strategy. CONCLUSION:
      The results of the SAFE trial and a subgroup analysis of SAFE data suggest that
      colloids should be avoided in patients with trauma and traumatic brain injury.
      There are minimal differences in outcome between crystalloids and hypo-oncotic or
      iso-oncotic albumin for fluid resuscitation in severe sepsis; in select
      populations, such as patients undergoing cardiac surgery, the use of iso-oncotic
      albumin may confer a survival advantage and should be considered a first-line
      alternative.

PMID- 22997117
TI  - Reversal of dabigatran-induced bleeding with a prothrombin complex concentrate
      and fresh frozen plasma.
AB  - PURPOSE: The case of a patient for whom reversal of dabigatran-induced bleeding
      was performed with a prothrombin complex concentrate (PCC) and fresh frozen
      plasma (FFP) is reported. SUMMARY: An 85-year-old man arrived at the emergency
      department with complaints of generalized weakness, fatigue, and one episode of
      dark stool. The patient's medical history included hypertension, heart failure,
      stage III chronic kidney disease, cerebrovascular accident, prostate cancer,
      gastritis, esophagitis, diverticulosis, and a bleeding gastrointestinal ulcer.
      Laboratory test results revealed acute liver failure, acute kidney injury, and
      anemia. He was diagnosed with hemorrhagic shock secondary to bleeding in his
      upper gastrointestinal tract. A reversal strategy was implemented using 16 units
      of FFP and 2000 units of a three-factor PCC. After administration of these
      agents, the patient's hemoglobin concentration stabilized, and there were no
      further signs of overt bleeding, suggesting potential hemostasis. Confirmation of
      this reversal was not possible due to the effect of concomitant liver failure on
      the International Normalized Ratio and the activated partial thromboplastin time
      (aPTT), common variables used to measure coagulation. CONCLUSION: Treatment with
      a PCC and FFP was administered to an 85-year-old man diagnosed with hemorrhagic
      shock secondary to bleeding in his upper gastrointestinal tract in an effort to
      reverse the anticoagulant effects of dabigatran. Although the patient's
      hemoglobin levels stabilized and his aPTT values decreased after treatment, he
      died as a result of multiorgan failure.

PMID- 22997118
TI  - Implementation of a web-based medication tracking system in a large academic
      medical center.
AB  - PURPOSE: Pharmacy workflow efficiencies achieved through the use of an electronic
      medication-tracking system are described. METHODS: Medication dispensing
      turnaround times at the inpatient pharmacy of a large hospital were evaluated
      before and after transition from manual medication tracking to a Web-based
      tracking process involving sequential bar-code scanning and real-time monitoring
      of medication status. The transition was carried out in three phases: (1) a
      workflow analysis, including the identification of optimal points for medication
      scanning with hand-held wireless devices, (2) the phased implementation of an
      automated solution and associated hardware at a central dispensing pharmacy and
      three satellite locations, and (3) postimplementation data collection to evaluate
      the impact of the new tracking system and areas for improvement. RESULTS:
      Relative to the manual tracking method, electronic medication tracking allowed
      the capture of far more data points, enabling the pharmacy team to delineate the
      time required for each step of the medication dispensing process and to identify
      the steps most likely to involve delays. A comparison of baseline and
      postimplementation data showed substantial reductions in overall medication
      turnaround times with the use of the Web-based tracking system (time reductions
      of 45% and 22% at the central and satellite sites, respectively). In addition to
      more accurate projections and documentation of turnaround times, the Web-based
      tracking system has facilitated quality-improvement initiatives. CONCLUSION:
      Implementation of an electronic tracking system for monitoring the delivery of
      medications provided a comprehensive mechanism for calculating turnaround times
      and allowed the pharmacy to identify bottlenecks within the medication
      distribution system. Altering processes removed these bottlenecks and decreased
      delivery turnaround times.

PMID- 22997119
TI  - Effects of a direct refill program for automated dispensing cabinets on
      medication-refill errors.
AB  - PURPOSE: The effects of a direct refill program for automated dispensing cabinets
      (ADCs) on medication-refill errors were studied. METHODS: This study was
      conducted in designated acute care areas of a 386-bed academic medical center. A
      wholesaler-to-ADC direct refill program, consisting of prepackaged delivery of
      medications and bar-code-assisted ADC refilling, was implemented in the inpatient
      pharmacy of the medical center in September 2009. Medication-refill errors in 26
      ADCs from the general medicine units, the infant special care unit, the surgical
      and burn intensive care units, and intermediate units were assessed before and
      after the implementation of this program. Medication-refill errors were defined
      as an ADC pocket containing the wrong drug, wrong strength, or wrong dosage form.
      RESULTS: ADC refill errors decreased by 77%, from 62 errors per 6829 refilled
      pockets (0.91%) to 8 errors per 3855 refilled pockets (0.21%) (p < 0.0001). The
      predominant error type detected before the intervention was the incorrect
      medication (wrong drug, wrong strength, or wrong dosage form) in the ADC pocket.
      Of the 54 incorrect medications found before the intervention, 38 (70%) were
      loaded in a multiple-drug drawer. After the implementation of the new refill
      process, 3 of the 5 incorrect medications were loaded in a multiple-drug drawer.
      There were 3 instances of expired medications before and only 1 expired
      medication after implementation of the program. CONCLUSION: A redesign of the ADC
      refill process using a wholesaler-to-ADC direct refill program that included
      delivery of prepackaged medication and bar-code-assisted refill significantly
      decreased the occurrence of ADC refill errors.

PMID- 22997120
TI  - Permeability of gloves to selected chemotherapeutic agents after treatment with
      alcohol or isopropyl alcohol.
AB  - PURPOSE: The results of a study to help identify the best glove protection for
      health care professionals frequently exposed to cytotoxic agents are reported.
      METHODS: The permeation of 17 cytotoxic drugs through different glove materials
      and glove combinations was studied under the conditions of simulated dynamic
      contact (e.g., friction, stretching), a temperature of 37  degrees C (normal body
      temperature), different exposure times (30 and 60 minutes), and a 15-minute
      pretreatment with 70% alcohol or isopropyl alcohol. For 6 drugs, permeability was
      further evaluated at a temperature of 43  degrees C with different double-gloving
      combinations in order to assess the risk of health care worker exposure during
      the administration of hyperthermic intraperitoneal chemotherapy (HIPEC). All
      evaluated glove products were provided by one manufacturer. Analytical
      measurements were performed in triplicate using chromatographic and spectrometric
      techniques. RESULTS: None of the gloves exhibited permeation exceeding European
      standard EN 374-3 (1000 ng/cm(2).min) or American standard ASTM F739-07 (100
      ng/cm(2).min); for a few drugs, glove permeation exceeded ASTM D6978-05 (10
      ng/cm(2).min). The highest permeation rates (66.5 and 36.3 ng/cm(2).min) were
      observed with two natural rubber latex products exposed for 60 minutes to
      carmustine. None of the evaluated double-gloving combinations displayed any
      detected permeation at 43  degrees C, confirming that they can be used safely
      during HIPEC. CONCLUSION: Gloves evaluated with a dynamic permeation testing
      device at 37  degrees C after pretreatment with alcohol or isopropyl alcohol
      showed permeation rates by selected cytotoxic drugs of <100 ng/cm(2).min after 30
      or 60 minutes of drug exposure. Undergloves alone and glove-glove and glove
      underglove combinations showed no detectable permeation in tests performed at 43 
      degrees C.

PMID- 22997121
TI  - Significant publications on infectious diseases pharmacotherapy in 2011.
AB  - PURPOSE: Important articles on topics pertinent to infectious diseases (ID)
      pharmacotherapy published in prominent peer-reviewed journals in 2011 are
      summarized. SUMMARY: Pharmacists, physicians, and researchers from the Houston
      Infectious Diseases Network were asked to nominate articles published in 2011
      that they perceived as having a significant impact on the field of ID
      pharmacotherapy. The resulting list, comprising 10 articles related to human
      immunodeficiency virus (HIV) disease or acquired immune deficiency syndrome
      (AIDS) and 38 articles on a broad range of other ID-related topics, was sent to
      members of the Society of Infectious Diseases Pharmacists (SIDP) for evaluation
      via an Internet survey. The survey participants were asked to select 10 articles
      from the list of general ID articles and 1 article from the HIV- or AIDS-related
      articles that they viewed as having the most impact on the field. Of the 328 SIDP
      members surveyed, 120 (37%) ranked the non-HIV-related papers and 55 (17%) ranked
      the HIV-related papers. The 12 highest-ranked items-including 3 guidelines-are
      summarized here. CONCLUSION: Due to the increasing number of articles published
      each year, it is difficult to maintain a current knowledge of significant
      publications in the field of ID pharmacotherapy. This review of the key articles
      in 2011 may be helpful to the nonspecialist clinician by lessening this burden.

PMID- 22997122
TI  - Initiation of an emergency department pharmacy program during economically
      challenging times.
AB  - PURPOSE: The initiation of a medication reconciliation program and other pharmacy
      services in the emergency department (ED) of a community hospital is described.
      SUMMARY: Despite a lack of funding for additional staff, the pharmacy department
      of a community hospital led an initiative to establish an ED pharmacy program; a
      major goal of the program was to address errors and inconsistencies in ED
      admission and discharge medication reconciliations. Implementing the program in a
      cost-neutral manner required the realignment of staff duties and schedules and an
      arrangement with the hospital's off-site central order-entry pharmacy contractor
      for expanded coverage hours. Other challenges during program implementation
      included securing ED workspace that afforded high visibility and easy access to
      the pharmacist and ensuring that pharmacy staff were qualified to provide
      critical care services (e.g., advanced life support, attendance at code
      responses, critical care drug information). After two months of operation, a
      review of a random sample (n = 102) of admission medication reconciliations
      indicated that those performed by pharmacists were significantly (p < 0.05) more
      likely than those conducted by nurses to meet specified accuracy criteria. An
      informal survey of ED physicians and nurses indicated that pharmacist involvement
      on the ED team was generally well received and viewed as integral to optimal ED
      services. CONCLUSION: Implementation of an ED pharmacist program improved the
      admission medication reconciliation process and provided additional services to
      improve patient safety and quality of care.

PMID- 22997123
TI  - A solution to an unmet need: pharmacy specialists in medication-use systems and
      technology.

PMID- 22997125
TI  - A concatenational graph evolution aging model.
AB  - Modeling the long-term face aging process is of great importance for face
      recognition and animation, but there is a lack of sufficient long-term face aging
      sequences for model learning. To address this problem, we propose a
      CONcatenational GRaph Evolution (CONGRE) aging model, which adopts decomposition
      strategy in both spatial and temporal aspects to learn long-term aging patterns
      from partially dense aging databases. In spatial aspect, we build a graphical
      face representation, in which a human face is decomposed into mutually
      interrelated subregions under anatomical guidance. In temporal aspect, the long
      term evolution of the above graphical representation is then modeled by
      connecting sequential short-term patterns following the Markov property of aging
      process under smoothness constraints between neighboring short-term patterns and
      consistency constraints among subregions. The proposed model also considers the
      diversity of face aging by proposing probabilistic concatenation strategy between
      short-term patterns and applying scholastic sampling in aging prediction. In
      experiments, the aging prediction results generated by the learned aging models
      are evaluated both subjectively and objectively to validate the proposed model.

PMID- 22997126
TI  - Fast recursive computation of 3D geometric moments from surface meshes.
AB  - A new exact algorithm is proposed to compute the 3D geometric moments of a
      homogeneous shape defined by an unstructured triangulation of its surface. This
      algorithm relies on the analytical integration of the moments on tetrahedra
      defined by the surface triangles and a central point and on a set of recurrent
      relationships between the corresponding integrals, and achieves linear running
      time complexities with respect to the number of triangles in the surface mesh and
      with respect to the number of moments that are computed. This effectively reduces
      the complexity for computing moments up to order N from N^6 to N^3 with respect
      to the fastest previously proposed exact algorithm.

PMID- 22997127
TI  - Learning image similarity from Flickr groups using fast kernel machines.
AB  - Measuring image similarity is a central topic in computer vision. In this paper,
      we propose to measure image similarity by learning from the online Flickr image
      groups. We do so by: Choosing 103 Flickr groups, building a one-versus-all
      multiclass classifier to classify test images into a group, taking the set of
      responses of the classifiers as features, calculating the distance between
      feature vectors to measure image similarity. Experimental results on the Corel
      dataset and the PASCAL VOC 2007 dataset show that our approach performs better on
      image matching, retrieval, and classification than using conventional visual
      features. To build our similarity measure, we need one-versus-all classifiers
      that are accurate and can be trained quickly on very large quantities of data. We
      adopt an SVM classifier with a histogram intersection kernel. We describe a novel
      fast training algorithm for this classifier: the Stochastic Intersection Kernel
      MAchine (SIKMA) training algorithm. This method can produce a kernel classifier
      that is more accurate than a linear classifier on tens of thousands of examples
      in minutes.

PMID- 22997128
TI  - Recognizing gestures by learning local motion signatures of HOG descriptors.
AB  - We introduce a new gesture recognition framework based on learning local motion
      signatures (LMSs) of HOG descriptors introduced by [1]. Our main contribution is
      to propose a new probabilistic learning-classification scheme based on a reliable
      tracking of local features. After the generation of these LMSs computed on one
      individual by tracking Histograms of Oriented Gradient (HOG) [2] descriptor, we
      learn a codebook of video-words (i.e., clusters of LMSs) using k-means algorithm
      on a learning gesture video database. Then, the video-words are compacted to a
      code-book of codewords by the Maximization of Mutual Information (MMI) algorithm.
      At the final step, we compare the LMSs generated for a new gesture w.r.t. the
      learned code-book via the k-nearest neighbors (k-NN) algorithm and a novel voting
      strategy. Our main contribution is the handling of the N to N mapping between
      codewords and gesture labels within the proposed voting strategy. Experiments
      have been carried out on two public gesture databases: KTH [3] and IXMAS [4].
      Results show that the proposed method outperforms recent state-of-the-art
      methods.

PMID- 22997129
TI  - Scalable active learning for multiclass image classification.
AB  - Machine learning techniques for computer vision applications like object
      recognition, scene classification, etc., require a large number of training
      samples for satisfactory performance. Especially when classification is to be
      performed over many categories, providing enough training samples for each
      category is infeasible. This paper describes new ideas in multiclass active
      learning to deal with the training bottleneck, making it easier to train large
      multiclass image classification systems. First, we propose a new interaction
      modality for training which requires only yes-no type binary feedback instead of
      a precise category label. The modality is especially powerful in the presence of
      hundreds of categories. For the proposed modality, we develop a Value-of
      Information (VOI) algorithm that chooses informative queries while also
      considering user annotation cost. Second, we propose an active selection measure
      that works with many categories and is extremely fast to compute. This measure is
      employed to perform a fast seed search before computing VOI, resulting in an
      algorithm that scales linearly with dataset size. Third, we use locality
      sensitive hashing to provide a very fast approximation to active learning, which
      gives sublinear time scaling, allowing application to very large datasets. The
      approximation provides up to two orders of magnitude speedups with little loss in
      accuracy. Thorough empirical evaluation of classification accuracy, noise
      sensitivity, imbalanced data, and computational performance on a diverse set of
      image datasets demonstrates the strengths of the proposed algorithms.

PMID- 22997130
TI  - Joint modeling of hierarchically clustered and overdispersed non-gaussian
      continuous outcomes for comet assay data.
AB  - Multivariate longitudinal or clustered data are commonly encountered in clinical
      trials and toxicological studies. Typically, there is no single standard endpoint
      to assess the toxicity or efficacy of the compound of interest, but co-primary
      endpoints are available to assess the toxic effects or the working of the
      compound. Modeling the responses jointly is thus appealing to draw overall
      inferences using all responses and to capture the association among the
      responses. Non-Gaussian outcomes are often modeled univariately using exponential
      family models. To accommodate both the overdispersion and hierarchical structure
      in the data, Molenberghs et al. A family of generalized linear models for
      repeated measures with normal and conjugate random effects. Statistical Science
      2010; 25:325-347 proposed using two separate sets of random effects. This papers
      considers a model for multivariate data with hierarchically clustered and
      overdispersed non-Gaussian data. Gamma random effect for the over-dispersion and
      normal random effects for the clustering in the data are being used. The two
      outcomes are jointly analyzed by assuming that the normal random effects for both
      endpoints are correlated. The association structure between the response is
      analytically derived. The fit of the joint model to data from a so-called comet
      assay are compared with the univariate analysis of the two outcomes.

PMID- 22997131
TI  - Pitted terrain on Vesta and implications for the presence of volatiles.
AB  - We investigated the origin of unusual pitted terrain on asteroid Vesta, revealed
      in images from the Dawn spacecraft. Pitted terrain is characterized by irregular
      rimless depressions found in and around several impact craters, with a distinct
      morphology not observed on other airless bodies. Similar terrain is associated
      with numerous martian craters, where pits are thought to form through degassing
      of volatile-bearing material heated by the impact. Pitted terrain on Vesta may
      have formed in a similar manner, which indicates that portions of the surface
      contain a relatively large volatile component. Exogenic materials, such as water
      rich carbonaceous chondrites, may be the source of volatiles, suggesting that
      impactor materials are preserved locally in relatively high abundance on Vesta
      and that impactor composition has played an important role in shaping the
      asteroid's geology.

PMID- 22997132
TI  - Planetary science. A golden spike for planetary science.

PMID- 22997133
TI  - Germ cell migration across Sertoli cell tight junctions.
AB  - The blood-testis barrier includes strands of tight junctions between somatic
      Sertoli cells that restricts solutes from crossing the paracellular space,
      creating a microenvironment within seminiferous tubules and providing immune
      privilege to meiotic and postmeiotic cells. Large cysts of germ cells transit the
      Sertoli cell tight junctions (SCTJs) without compromising their integrity. We
      used confocal microscopy to visualize SCTJ components during germ cell cyst
      migration across the SCTJs. Cysts become enclosed within a network of transient
      compartments fully bounded by old and new tight junctions. Dissolution of the old
      tight junctions releases the germ cells into the adluminal compartment, thus
      completing transit across the blood-testis barrier. Claudin 3, a tight junction
      protein, is transiently incorporated into new tight junctions and then replaced
      by claudin 11.

PMID- 22997134
TI  - Detecting causality in complex ecosystems.
AB  - Identifying causal networks is important for effective policy and management
      recommendations on climate, epidemiology, financial regulation, and much else. We
      introduce a method, based on nonlinear state space reconstruction, that can
      distinguish causality from correlation. It extends to nonseparable weakly
      connected dynamic systems (cases not covered by the current Granger causality
      paradigm). The approach is illustrated both by simple models (where, in contrast
      to the real world, we know the underlying equations/relations and so can check
      the validity of our method) and by application to real ecological systems,
      including the controversial sardine-anchovy-temperature problem.

PMID- 22997135
TI  - Elemental mapping by Dawn reveals exogenic H in Vesta's regolith.
AB  - Using Dawn's Gamma Ray and Neutron Detector, we tested models of Vesta's
      evolution based on studies of howardite, eucrite, and diogenite (HED) meteorites.
      Global Fe/O and Fe/Si ratios are consistent with HED compositions. Neutron
      measurements confirm that a thick, diogenitic lower crust is exposed in the
      Rheasilvia basin, which is consistent with global magmatic differentiation.
      Vesta's regolith contains substantial amounts of hydrogen. The highest hydrogen
      concentrations coincide with older, low-albedo regions near the equator, where
      water ice is unstable. The young, Rheasilvia basin contains the lowest
      concentrations. These observations are consistent with gradual accumulation of
      hydrogen by infall of carbonaceous chondrites--observed as clasts in some
      howardites--and subsequent removal or burial of this material by large impacts.

PMID- 22997136
TI  - Genomic variation in seven Khoe-San groups reveals adaptation and complex African
      history.
AB  - The history of click-speaking Khoe-San, and African populations in general,
      remains poorly understood. We genotyped ~2.3 million single-nucleotide
      polymorphisms in 220 southern Africans and found that the Khoe-San diverged from
      other populations >=100,000 years ago, but population structure within the Khoe
      San dated back to about 35,000 years ago. Genetic variation in various sub
      Saharan populations did not localize the origin of modern humans to a single
      geographic region within Africa; instead, it indicated a history of admixture and
      stratification. We found evidence of adaptation targeting muscle function and
      immune response; potential adaptive introgression of protection from ultraviolet
      light; and selection predating modern human diversification, involving skeletal
      and neurological development. These new findings illustrate the importance of
      African genomic diversity in understanding human evolutionary history.

PMID- 22997138
TI  - Crystal structure of a soluble form of human CD73 with ecto-5'-nucleotidase
      activity.
AB  - CD73 is a dimeric ecto-5'-nucleotidase that is expressed on the exterior side of
      the plasma membrane. CD73 has important regulatory functions in the extracellular
      metabolism of certain nucleoside monophosphates, in particular adenosine
      monophosphate, and has been linked to a number of pathological conditions such as
      cancer and myocardial ischaemia. Here, we present the crystal structure of a
      soluble form of human soluble CD73 (sCD73) at 2.2 A resolution, a truncated form
      of CD73 that retains ecto-5'-nucleotidase activity. With this structure we
      obtained insight into the dimerisation of CD73, active site architecture, and a
      sense of secondary modifications of the protein. The crystal structure reveals a
      conserved loop that is directly involved in the dimer-dimer interaction showing
      that the two subunits of the dimer are not linked by disulfide bridges. Using
      biophotonic microarray imaging we were able to confirm glycosylation of the
      enzyme and show that the enzyme is decorated with a variety of oligosaccharide
      structures. The crystal structure of sCD73 will aid the design of inhibitors or
      activator molecules for the treatment of several diseases and prove useful in
      explaining the possible roles of single nucleotide polymorphisms in physiology
      and disease.

PMID- 22997139
TI  - Potentiodynamic polarization study on electropolished nitinol vascular implants.
AB  - The electrochemical properties of electropolished Nitinol vascular implants
      manufactured in a serial-production manner starting with laser cutting of tubing
      and ending with electropolishing and final inspection were analyzed and evaluated
      over a time period of 1 year. Potentiodynamic polarization tests in phosphate
      buffered saline were conducted on over 1250 Nitinol implants covering the entire
      serial production range at ADMEDES Schuessler GmbH - from tiny stents for
      neurovascular applications up to large heart valve frames. Breakdown potentials
      were evaluated and correlated to product group, properties of the semifinished
      material and raw material supplier. Results of this study give clear indications
      for the interrelation between material quality and the event of electrochemical
      breakdown in a potentiodynamic polarization test.

PMID- 22997137
TI  - Latest developments in experimental and computational approaches to characterize
      protein-lipid interactions.
AB  - Understanding the functional roles of all the molecules in cells is an ultimate
      goal of modern biology. An important facet is to understand the functional
      contributions from intermolecular interactions, both within a class of molecules
      (e.g. protein-protein) or between classes (e.g. protein-DNA). While the
      technologies for analyzing protein-protein and protein-DNA interactions are well
      established, the field of protein-lipid interactions is still relatively nascent.
      Here, we review the current status of the experimental and computational
      approaches for detecting and analyzing protein-lipid interactions. Experimental
      technologies fall into two principal categories, namely solution-based and array
      based methods. Computational methods include large-scale data-driven analyses and
      predictions/dynamic simulations based on prior knowledge of experimentally
      identified interactions. Advances in the experimental technologies have led to
      improved computational analyses and vice versa, thereby furthering our
      understanding of protein-lipid interactions and their importance in biological
      systems.

PMID- 22997140
TI  - Removal of cefalexin using yeast surface-imprinted polymer prepared by atom
      transfer radical polymerization.
AB  - The first use of yeast as a support in the molecular imprinting field combined
      with atom transfer radical polymerization was described. Then, the as-prepared
      molecularly imprinted polymers were characterized by Fourier transmission
      infrared spectrometry, scanning electron microscope, thermogravimetric analysis,
      and elemental analysis. The obtained imprinted polymers demonstrated elliptical
      shaped particles with the thickness of imprinting layer of 0.63 MUm. The batch
      mode experiments were adopted to investigate the adsorption equilibrium,
      kinetics, and selectivity. The kinetic properties of imprinted polymers were well
      described by the pseudo-second-order kinetic equation, indicating the chemical
      process was the rate-limiting step for the adsorption of cefalexin (CFX). The
      equilibrium data were well fitted by the Freundlich isotherm, and the
      multimolecular layers adsorption capacity of imprinted polymers was 34.07 mg g(
      1)  at 298 K. The selectivity analysis suggested that the imprinted polymers
      exhibited excellent selective recognition for CFX in the presence of other
      compounds with related structure. Finally, the analytical method based on the
      imprinted polymers extraction coupled with high-performance liquid chromatograph
      was successfully used for CFX analysis in spiked pork and water samples.

PMID- 22997141
TI  - Ikaros (IKZF1) alterations and minimal residual disease at day 15 assessed by
      flow cytometry predict prognosis of childhood BCR/ABL-negative acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Recently, several studies have demonstrated a negative prognostic
      impact of Ikaros (IKZF1) gene alterations in acute lymphoblastic leukemia (ALL).
      However, controversies still exist regarding the impact of IKZF1 in current
      treatment protocols. PROCEDURE: We simultaneously detected IKZF1 gene deletions
      by multiplex ligation-dependent probe amplification and gene expression of IKZF1
      isoforms in 206 children with BCR/ABL-negative ALL treated with ALL IC-BFM 2002
      protocol, in which risk stratification was not based on minimal residual disease
      (MRD), and validated the results on a cohort of 189 patients treated with MRD
      directed ALL-BFM 2000 protocol. RESULTS: Deletion of IKZF1 was present in 14 of
      206 (7%) ALL IC patients. Interestingly, gene expression did not completely
      correlate with the deletion status in either cohort. Deletions were not always
      reflected in the gene expression of dominant-negative isoforms, and conversely, 7
      of 395 (2%) non-deleted cases overexpressed dominant-negative isoform Ik6. IKZF1
      deletions significantly affected event-free survival (EFS) of the ALL IC cohort
      (41 +/- 14% vs. 86 +/- 3%, P < 0.0001). Regarding IKZF1 isoforms, only Ik6
      overexpression had negative prognostic impact (EFS 50 +/- 16% vs. 85 +/- 3%, P =
      0.003). In multivariate analysis, which included ALL IC risk criteria, flow
      cytometric MRD and IKZF1 alterations, day 15 MRD and IKZF1 deletion status
      displayed an independent prognostic impact. CONCLUSIONS: We show that MRD
      directed treatment diminishes prognostic impact of IKZF1 alterations. However,
      IKZF1 status alone or combined with day 15 flow cytometry can significantly
      improve risk stratification within BFM protocols at centers that do not perform
      antigen-receptor-based MRD monitoring.

PMID- 22997142
TI  - Highly reproducible surface-enhanced Raman spectra on semiconductor SnO2
      octahedral nanoparticles.
AB  - Highly reproducible surface-enhanced Raman scattering (SERS) spectra are obtained
      on the surface of SnO(2) octahedral nanoparticles. The spot-to-spot SERS signals
      show a relative standard deviation (RSD) consistently below 20 % in the intensity
      of the main Raman peaks of 4-mercaptobenzoic acid (4-MBA) and 4-nitrobenzenethiol
      (4-NBT), indicating good spatial uniformity and reproducibility. The SERS signals
      are believed to mainly originate from a charge-transfer (CT) mechanism. Time
      dependent density functional theory (TD-DFT) is used to simulate the SERS
      spectrum and interpret the chemical enhancement mechanism in the experiment. The
      research extends the application of SERS and also establishes a new uniform SERS
      substrate.

PMID- 22997143
TI  - Analysis of the rat hypothalamus proteome by data-independent label-free LC
      MS/MS.
AB  - Studies of neuronal, endocrine, and metabolic disorders would be facilitated by
      characterization of the hypothalamus proteome. Protein extracts prepared from 16
      whole rat hypothalami were measured by data-independent label-free nano LC-MS/MS.
      Peptide features were detected, aligned, and searched against a rat Swiss-Prot
      database using ProteinLynx Global Server v.2.5. The final combined dataset
      comprised 21 455 peptides, corresponding to 622 unique proteins, each identified
      by a minimum of two distinct peptides. The majority of the proteins (69%) were
      cytosolic, and 16% were membrane proteins. Important proteins involved in
      neurological and synaptic function were identified including several members of
      the Ras-related protein family and proteins involved in glutamate biosynthesis.

PMID- 22997144
TI  - Exercise intensity self-regulation using the OMNI scale in children with cystic
      fibrosis.
AB  - Prescribing exercise at intensities that improve fitness is difficult in children
      with cystic fibrosis (CF) due to ventilatory limitations and fluctuating health
      status. Our aim was to determine if children with CF could regulate the intensity
      of cycle ergometer and treadmill exercise using target ratings of perceived
      exertion (RPE) derived from the Children's OMNI Scale. We examined prescription
      congruence (similar oxygen consumption [VO2] and heart rate [HR] for target RPE)
      and intensity discrimination (different VO2 and HR for different RPEs), from
      cycle to cycle and cycle to treadmill. Subjects were 24 children (12 male, 12
      female), aged 10-17 years with varying disease severity. Each child participated
      in one orientation, one estimation trial (graded maximal exercise test), and two
      production trials (cycle and treadmill, alternating between RPE 4 and 7). At RPE
      4, congruence was evident for both VO2 and HR on the treadmill. On the cycle at
      RPE 4, VO2 was significantly higher only in the first production trial, although
      HRs tended to be higher in the production trials than the estimation trial.
      Prescription congruence was also supported at RPE 7, with no significant
      differences in VO2 or HR between estimation and production trials on cycle or
      treadmill. Results fully supported intensity discrimination, with significant
      differences between VO2 and HR at RPE 4 and 7 (P < 0.0001). Children with CF
      appear capable of using the OMNI Scale to regulate cycle and treadmill exercise
      intensity. Training using this methodology has the potential to promote fitness
      in children with CF of varying severity.

PMID- 22997145
TI  - Mathematical modeling of cross-linking monomer elution from resin-based dental
      composites.
AB  - Elution of potentially toxic substances, including monomers, from resin-based
      dental composites may affect the biocompatibility of these materials in clinical
      conditions. In addition to the amounts of eluted monomers, mathematical modeling
      of elution kinetics reveals composite restorations as potential chronic sources
      of leachable monomers. The aim of this work was to experimentally quantify
      elution of main cross-linking monomers from four commercial composites and offer
      a mathematical model of elution kinetics. Composite samples (n = 7 per group) of
      Filtek Supreme XT (3M ESPE), Tetric EvoCeram (Ivoclar Vivadent), Admira (Voco),
      and Filtek Z250 (3M ESPE) were prepared in 2-mm thick Teflon moulds and cured
      with halogen or light-emitting diode light. Monomer elution in ethanol and water
      was analyzed using high-performance liquid chromatography up to 28 days
      postimmersion. The mathematical model was expressed as a sum of two exponential
      regression functions representing the first-order kinetics law. Elution kinetics
      in all cases followed the same mathematical model though differences in rate
      constants as well as the extent of monomer elution were material-, LCU-, medium
      dependent. The proposed mechanisms of elution indicate fast elution from surface
      and subsurface layers and up to 100 times slower monomer extraction from the bulk
      polymer.

PMID- 22997146
TI  - Retention characteristics of water-soluble compounds on water-holding adsorbents
      with immobilized zwitterionic copolymers having different ionicities.
AB  - Three kinds of water-holding adsorbents with immobilized zwitterionic copolymers
      having different cationic ionicities were synthesized. To investigate the
      influence of the charge balance and the ionicity of the cation site, the
      retention properties of the water-soluble solutes on the zwitterionic adsorbents
      were measured by HPLC. These adsorbents had high water contents, and the
      hydrating water contents depended on the amounts of immobilized copolymer. The
      retentions of water-soluble solutes depended on the hydrophilic interaction, and
      were in the order of logP(o/w)  (logarithm of octanol-water partition
      coefficient). This suggests that the partition to the hydration layer was the
      main retention mechanism on the zwitterionic adsorbents. On the other hand, the
      electrostatic interaction based on the cation site on the adsorbents was also
      observed. The electrostatic interaction could be reduced by decreasing the
      ionicity of the cation sites. These results indicate that the retentions of the
      water-soluble solutes on the zwitterionic adsorbents were greatly influenced by
      the ionicity of the cation sites on the adsorbents.

PMID- 22997148
TI  - Impaired growth, hematopoietic colony formation, and ribosome maturation in human
      cells depleted of Shwachman-Diamond syndrome protein SBDS.
AB  - BACKGROUND: Shwachman-Diamond syndrome (SDS), associated with SBDS mutations, is
      characterized by pancreatic exocrine dysfunction and marrow failure. Sdo1, the
      yeast ortholog of SBDS, is implicated in maturation of the 60S ribosomal subunit,
      with delayed export of 60S-like particles from the nucleoplasm when depleted.
      Sdo1 is needed for release of the anti-subunit association factor Tif6 from 60S
      subunits, and Tif6 may not be recycled to the nucleus when Sdo1 is absent.
      METHODS: To clarify the role of SBDS in human ribosome function, TF-1
      erythroleukemia and A549 lung carcinoma cells were transfected with vectors
      expressing RNAi against SBDS. RESULTS: Growth and hematopoietic colony forming
      potential of TF-1 knockdown cells were markedly hindered when compared to
      controls. To analyze the effect of SBDS on 60S subunit maturation in A549 cells,
      subunit localization was assessed by transfection with a vector expressing a
      fusion between human RPL29 and GFP: we found a higher percentage of SBDS-depleted
      cells with nuclear localization of 60S subunits. Polysome analysis of TF-1
      knockdown cells showed a decrease in free 60S and 80S subunits. We also analyzed
      the levels of eIF6 (human ortholog of Tif6) following near-complete knockdown of
      SBDS in TF-1 cells and found an approximately 20% increase in the amount of eIF6
      associated with the 60S subunit. CONCLUSIONS: We conclude that knockdown of SBDS
      leads to growth inhibition and defects in ribosome maturation, suggesting a role
      for wild-type SBDS in nuclear export of pre-60S subunits. Furthermore, knockdown
      of SBDS may interfere with eIF6 recycling.

PMID- 22997149
TI  - Reverse vesicles of ferrum laurate metallosurfactant in non-aqueous solution
      dried to produce solid shells.
AB  - Ferrum laurate [Fe(OOCC(11) H(23))(3)] metallosurfactant can successfully self
      assemble into reversed vesicles in organic media such as pure CHCl(3) and a mixed
      solvent of CHCl(3) and CH(3)OH. Deformed solid vesicles, including collapsed
      erythrocyte-like and broken hollow shells, were obtained directly by slectively
      drying the organic solvents. The morphology of the reversed vesicles of
      metallosurfactant in the organic media to hardly solid shells is maintained and
      it is ascribed to the evaporation rate of the solvents and the interactions
      between ferrum laurate and solvents.

PMID- 22997150
TI  - Proteomic analysis of interactors for yeast protein arginine methyltransferase
      Hmt1 reveals novel substrate and insights into additional biological roles.
AB  - Protein arginine methylation is a PTM catalyzed by an evolutionarily conserved
      family of enzymes called protein arginine methyltransferases (PRMTs), with PRMT1
      being the most conserved member of this enzyme family. This modification has
      emerged to be an important regulator of protein functions. To better understand
      the role of PRMTs in cellular pathways and functions, we have carried out a
      proteomic profiling experiment to comprehensively identify the physical
      interactors of Hmt1, the budding yeast homolog for human PRMT1. Using a dual
      enzymatic digestion linear trap quadrupole/Orbitrap proteomic strategy, we
      identified a total of 108 proteins that specifically copurify with Hmt1 by tandem
      affinity purification. A reverse coimmunoprecipitation experiment was used to
      confirm Hmt1's physical association with Bre5, Mtr4, Snf2, Sum1, and Ssd1, five
      proteins that were identified as Hmt1-specific interactors in multiple biological
      replicates. To determine whether the identified Hmt1-interactors had the
      potential to act as an Hmt1 substrate, we used published bioinformatics
      algorithms that predict the presence and location of potential methylarginines
      for each identified interactor. One of the top hits from this analysis, Snf2, was
      experimentally confirmed as a robust substrate of Hmt1 in vitro. Overall, our
      data provide a feasible proteomic approach that aid in the better understanding
      of PRMT1's roles within a cell.

PMID- 22997151
TI  - Response to letter.

PMID- 22997152
TI  - Human adipose-derived stem cells and three-dimensional scaffold constructs: a
      review of the biomaterials and models currently used for bone regeneration.
AB  - In the past decade, substantial strides have been taken toward the use of human
      adipose-derived stromal/stem cells (hASC) in the regeneration of bone. Since the
      discovery of the hASC osteogenic potential, many models have combined hASC with
      biodegradable scaffold materials. In general, rats and immunodeficient (nude)
      mice models for nonweight bearing bone formation have led the way to assess hASC
      osteogenic potential in vivo. The goal of this review is to present an overview
      of the recent literature describing hASC osteogenesis in conjunction with three
      dimensional scaffolds for bone regeneration.

PMID- 22997153
TI  - A novel microextraction by packed sorbent-gas chromatography procedure for the
      simultaneous analysis of antiepileptic drugs in human plasma and urine.
AB  - A simple, accurate, and sensitive microextraction by packed sorbent-gas
      chromatography-mass spectrometry method has been developed for the simultaneous
      quantification of four antiepileptic drugs; oxcarbazepine, carbamazepine,
      phenytoin, and alprazolam in human plasma and urine as a tool for drug
      monitoring. Caffeine was used as internal standards for the electron ionization
      mode. An original pretreatment procedure on biological samples, based on
      microextraction in packed syringe using C(18)  as packing material gave high
      extraction yields (69.92-99.38%), satisfactory precision (RSD < 4.7%) and good
      selectivity. Linearity was found in the 0.1-500 ng/mL range for these drugs with
      limits of detection (LODs) between 0.0018 and 0.0036 ng/mL. Therefore, the method
      has been found to be suitable for the therapeutic drug monitoring of patients
      treated with oxcarbazepine, carbamazepine, phenytoin, and alprazolam. After
      validation, the method was successfully applied to some plasma samples from
      patients undergoing therapy with one or more of these drugs. A comparison of the
      detection limit with similar methods indicates high sensitivity of the present
      method over the earlier reported methods. The present method is applied for the
      analysis of these drugs in the real urine and plasma samples of the epileptic
      patients.

PMID- 22997154
TI  - Plasma microRNA profile as a predictor of early virological response to
      interferon treatment in chronic hepatitis B patients.
AB  - BACKGROUND: Interferon (IFN) and pegylated interferon (PEG-IFN) treatment of
      chronic hepatitis B leads to a sustained virological response in a limited
      proportion of patients and has considerable side effects. To find novel markers
      associated with prognosis of IFN therapy, we investigated whether a pretreatment
      plasma microRNA profile could be used to predict early virological response to
      IFN. METHODS: We performed microRNA microarray analysis of plasma samples from 94
      patients with chronic hepatitis B who received IFN therapy. The microRNA profiles
      from 13 liver biopsy samples were also measured. The OneR feature ranking and
      incremental feature selection method were used to rank and optimize the number of
      features in the model. Support vector machine prediction engine and jack-knife
      cross-validation were used to generate and evaluate the prediction model.
      RESULTS: The optimized model consisting of 11 microRNAs yielded a 74.2% overall
      accuracy in the training group and was independently confirmed in the test group
      (71.4% accuracy). Univariate and multivariate logistic regression analyses
      confirmed its independent association with early virological response (OR=7.35;
      P=2.12*10(-5)). Combining the microRNA profile with the alanine aminotransferase
      level improved the overall accuracy from 73.4% to 77.3%. Co-transfection of an
      HBV replicative construct with microRNA mimics revealed that let-7f, miR-939 and
      miR-638 were functionally associated with the HBV life cycle. CONCLUSIONS: The 11
      microRNA signatures in plasma, together with basic clinical variables, might
      provide an accurate method to assist in medication decisions and improve the
      overall sustained response to IFN treatment.

PMID- 22997155
TI  - A novel mutation in the SerpinC1 gene presenting as unprovoked neonatal cerebral
      sinus venous thrombosis in a kindred.
AB  - Antithrombin (AT) deficiency has been associated with an increased risk of
      pediatric cerebral sinus venous thrombosis (CSVT); but few cases of neonatal CSVT
      have been reported. We describe two half-siblings who presented with seizures in
      the first week of life and were found to have extensive CSVT with associated
      parenchymal and intraventricular hemorrhage. Both infants were found to have type
      1 AT deficiency. Sequencing of the SerpinC1 gene revealed a novel heterozygous
      mutation on exon 5 (c.1009C > T p.Q337X). Both infants were treated with
      anticoagulation and had recanalization of the dural sinuses on follow up imaging.

PMID- 22997147
TI  - Persistence of novel first-line antiretroviral regimes in a cohort of HIV
      positive subjects, CoRIS 2008-2010.
AB  - BACKGROUND: The aim of this study was to estimate the persistence of the most
      commonly used first-line combined antiretroviral regimens (cART) in HIV-infected
      adults in the CoRIS cohort. METHODS: CoRIS is an open prospective multicentre
      cohort of HIV-infected adults naive to cART at entry. Patients enrolled between
      January 2008 and June 2010 were included. The main outcome was treatment
      persistence, defined as time from cART initiation to first treatment change (TC).
      Cox models taking into account competing risks to estimate sub-hazard ratios
      (sHR) were performed. RESULTS: Of 1,512 patients, 919 (60.8%) initiated cART with
      the backbone tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) plus
      efavirenz (EFV), 252 (16.7%) plus lopinavir/ritonavir (LPV/r), 129 (8.5%) plus
      atazanavir/ritonavir (ATV/r), 110 (7.3%) plus darunavir/ritonavir (DRV/r) and 102
      (6.7%) plus nevirapine (NVP). Among 414 patients who switched therapy, reason for
      switching was available for 393. The most frequent reasons were toxicity (40%),
      simplification (14%) and treatment failure/resistance (13%). In multivariate
      analyses, there were significant differences in the risk of TC according to
      initial cART regimen (P<0.001). Initiating TDF plus FTC with NVP (sHR 1.94, 95%
      CI 1.38, 2.72) or LPV/r (sHR 1.89, 95% CI 1.45, 2.47) was associated with higher
      risk of TC than initiating with TDF plus FTC plus EFV. No differences in TC were
      found between initiating EFV versus ATV/r (sHR 1.29, 95% CI 0.89, 1.86) or DRV/r
      (sHR 0.98, 95% CI 0.59, 1.65) with TDF plus FTC as backbone. CONCLUSIONS:
      Switching from initial cART regimens is frequent, toxicity being the main reason
      for it. The significantly greater persistence of some combinations may be useful
      for making decisions when initiating cART.

PMID- 22997156
TI  - Expansion of necrotic core and shedding of Mertk receptor in human carotid
      plaques: a role for oxidized polyunsaturated fatty acids?
AB  - AIMS: Expansion of necrotic core (NC), a major feature responsible for plaque
      disruption, is likely the consequence of accelerated macrophage apoptosis coupled
      with defective phagocytic clearance (efferocytosis). The cleavage of the
      extracellular domain of Mer tyrosine kinase (Mertk) by metallopeptidase domain17
      (Adam17) has been shown to produce a soluble Mertk protein (sMer), which can
      inhibit efferocytosis. Herein, we analysed the expression and localization of
      Mertk and Adam17 in the tissue around the necrotic core (TANC) and in the
      periphery (P) of human carotid plaques. Then we studied the mechanisms of NC
      expansion by evaluating which components of TANC induce Adam17 and the related
      cleavage of the extracellular domain of Mertk. METHODS AND RESULTS: We studied 97
      human carotid plaques. The expression of Mertk and Adam17 was found to be higher
      in TANC than in P (P < 0.001). By immunohistochemistry, Mertk was higher than
      Adam17 in the area of TANC near to the lumen (P < 0.01) but much lower in the
      area close to NC (P < 0.01). The extract of this portion of TANC increased the
      expression (mRNA) of Adam17 and Mertk (P < 0.01) in macrophage-like THP-1 cells
      but it also induced the cleavage of the extracellular domain of Mertk, generating
      sMer in the medium (P < 0.01). This effect of TANC extract was most evoked by its
      content in F(2)-isoprostanes, hydroxyoctadecadienoic acids, and hydroxytetraenoic
      acids. CONCLUSION: Some oxidized derivatives of polyunsaturated fatty acids
      contained in TANC of human carotid plaques are strong inducers of Adam17, which
      in turn leads to the generation of sMer, which can inhibit efferocytosis.

PMID- 22997157
TI  - Macrophage migration inhibitory factor in the nucleus of solitary tract decreases
      blood pressure in SHRs.
AB  - AIMS: The macrophage migration inhibitory factor (MIF) is an intracellular
      inhibitor of the central nervous system actions of angiotensin II on blood
      pressure. Considering that angiotensin II actions at the nucleus of the solitary
      tract are important for the maintenance of hypertension in spontaneously
      hypertensive rats (SHRs), we tested if increased MIF expression in the nucleus of
      the solitary tract of SHR alters the baseline high blood pressure in these rats.
      METHODS AND RESULTS: Eight-week-old SHRs or normotensive rats were microinjected
      with the vector AAV2-CBA-MIF into the nucleus of the solitary tract, resulting in
      MIF expression predominantly in neurons. Rats also underwent recordings of the
      mean arterial blood pressure (MAP) and heart rate (via telemetry devices
      implanted in the abdominal aorta), cardiac- and baroreflex function. Injections
      of AAV2-CBA-MIF into the nucleus of the solitary tract of SHRs produced
      significant decreases in the MAP, ranging from 10 to 20 mmHg, compared with age
      matched SHRs that had received identical microinjections of the control vector
      AAV2-CBA-eGFP. This lowered MAP in SHRs was maintained through the end of the
      experiment at 31 days, and was associated with an improvement in baroreflex
      function to values observed in normotensive rats. In contrast to SHRs, similar
      increased MIF expression in the nucleus of the solitary tract of normotensive
      rats produced no changes in baseline MAP and baroreflex function. CONCLUSION:
      These results indicate that an increased expression of MIF within the nucleus of
      the solitary tract neurons of SHRs lowers blood pressure and restores baroreflex
      function.

PMID- 22997158
TI  - Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel
      block as a common teratogenic mechanism.
AB  - AIMS: Several drugs blocking the rapidly activating potassium (K(r)) channel
      cause malformations (including cardiac defects) and embryonic death in animal
      teratology studies. In humans, these drugs have an established risk for acquired
      long-QT syndrome and arrhythmia. Recently, associations between cardiac defects
      and spontaneous abortions have been reported for drugs widely used in pregnancy
      (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a
      common embryonic adverse-effect mechanism exists in the human, rat, and rabbit
      embryos, we made a comparative study of embryonic cardiomyocytes from all three
      species. METHODS AND RESULTS: Patch-clamp and quantitative-mRNA measurements of
      K(r) and slowly activating K (K(s)) channels were performed on human, rat, and
      rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal
      stages. The K(r) channel was present when the heart started to beat in all
      species, but was, in contrast to human and rabbit, lost in rats in late
      organogenesis. The specific K(r)-channel blocker E-4031 prolonged the action
      potential in a species- and development-dependent fashion, consistent with the
      observed K(r)-channel expression pattern and reported sensitive periods of
      developmental toxicity. E-4031 also increased the QT interval and induced 2:1
      atrio-ventricular block in multi-electrode array electrographic recordings of rat
      embryos. The K(s) channel was expressed in human and rat throughout the embryo
      foetal period but not in rabbit. CONCLUSION: This first comparison of mRNA
      expression, potassium currents, and action-potential characteristics, with and
      without a specific K(r)-channel blocker in human, rat, and rabbit embryos
      provides evidence of K(r)-channel inhibition as a common mechanism for embryonic
      malformations and death.

PMID- 22997159
TI  - Early repolarization in mice causes overestimation of ventricular activation time
      by the QRS duration.
AB  - AIMS: Transgenic mice are frequently used to investigate the role of genes
      involved in cardiac conduction. The QRS duration calculated from the
      electrocardiogram (ECG) is a commonly used measure for ventricular conduction
      time. However, the relation between ventricular activation and QRS duration
      calculated from a mouse surface ECG is not well understood. We aim to relate
      ventricular activation and repolarization patterns with the mouse ECG. METHODS
      AND RESULTS: Ventricular activation and repolarization patterns generated by high
      density optical mapping and a six-lead pseudo-ECG were compared in isolated mouse
      hearts. In addition, mouse ECGs were simulated in silico. Right-ventricular
      activation ends later than left-ventricular activation. Final activation
      coincided with the end of the QRS complex in leads III and aVF, but not in leads
      I, II, aVR, and aVL. The pattern of early repolarization (at 20% of
      repolarization, RT20) but not of RT50 or RT80 followed the activation pattern.
      After sodium channel blockade by ajmaline, total ventricular activation time
      increased by 10.0 ms, whereas QRS duration increased by only 2.1 ms. In mice
      carrying a mutation in Scn5a (1798insD), ventricular activation ended after the
      end of the QRS complex (12.9 +/- 0.1 vs. 10.8 +/- 0.3). CONCLUSION: In the mouse,
      ventricular myocardium activation and early repolarization waves are
      simultaneously present. This hampers unequivocal interpretation of the duration
      of the QRS complex as a measure of ventricular activation duration, especially
      when conduction is slowed. Under these conditions mapping of local activation and
      repolarization patterns is required for correct interpretation of the ECG.

PMID- 22997160
TI  - Boosting the pentose phosphate pathway restores cardiac progenitor cell
      availability in diabetes.
AB  - AIMS: Diabetes impinges upon mechanisms of cardiovascular repair. However, the
      biochemical adaptation of cardiac stem cells to sustained hyperglycaemia remains
      largely unknown. Here, we investigate the molecular targets of high glucose
      induced damage in cardiac progenitor cells (CPCs) from murine and human hearts
      and attempt safeguarding CPC viability and function through reactivation of the
      pentose phosphate pathway. METHODS AND RESULTS: Type-1 diabetes was induced by
      streptozotocin. CPC abundance was determined by flow cytometry. Proliferating
      CPCs were identified in situ by immunostaining for the proliferation marker Ki67.
      Diabetic hearts showed marked reduction in CPC abundance and proliferation when
      compared with controls. Moreover, Sca-1(pos) CPCs isolated from hearts of
      diabetic mice displayed reduced activity of key enzymes of the pentose phosphate
      pathway, glucose-6-phosphate dehydrogenase (G6PD), and transketolase, increased
      levels of superoxide and advanced glucose end-products (AGE), and inhibition of
      the Akt/Pim-1/Bcl-2 signalling pathway. Similarly, culture of murine CPCs or
      human CD105(pos) progenitor cells in high glucose inhibits the pentose phosphate
      and pro-survival signalling pathways, leading to the activation of apoptosis. In
      vivo and in vitro supplementation with benfotiamine reactivates the pentose
      phosphate pathway and rescues CPC availability and function. This benefit is
      abrogated by either G6PD silencing by small interfering RNA (siRNA) or Akt
      inhibition by dominant-negative Akt. CONCLUSION: We provide new evidence of the
      negative impact of diabetes and high glucose on mechanisms controlling CPC redox
      state and survival. Boosting the pentose phosphate pathway might represent a
      novel mechanistic target for protection of CPC integrity.

PMID- 22997162
TI  - Arene-Ru(II) complexes of curcumin exert antitumor activity via proteasome
      inhibition and apoptosis induction.
AB  - Organometallic ruthenium(II) complexes of general formula [(eta(6)
      arene)Ru(curcuminato)Cl], with arene being p-iPrC6 H4Me (1), C6H6 (2), and C6Me6
      (3), were synthesized, characterized, and evaluated for their antitumor effects.
      Specifically, we explored their ability to regulate the proteasome, a validated
      pharmacological target in cancer treatment. Ruthenium complexes inhibited
      isolated proteasomes to various extents, with the biological activity of these
      complexes depending on the nature of the bound arene; in particular, [(eta(6)
      arene)Ru(curcuminato)Cl] 2 suppressed proteasomal activities more potently than
      1, 3, or free curcumin. Each complex also inhibited proteasomes in cultured colon
      cancer cells and consequently triggered apoptosis, with the [(eta(6)
      benzene)Ru(curcuminato)Cl] complex 2 being the most active. The influence on the
      oxidative status of HCT116 cells and the DNA binding ability of the [(eta(6)
      arene)Ru(curcuminato)Cl] complexes were studied. Complex 2 showed the highest
      antioxidant capacity; moreover, complexes 1 and 2 were shown to bind isolated DNA
      with higher affinity (up to threefold) than free curcumin. Collectively, our
      results demonstrate that the complexation of curcumin with ruthenium(II) is a
      promising starting point for the development of curcumin-based anticancer drugs.

PMID- 22997161
TI  - Aquaporin 1, Nox1, and Ask1 mediate oxidant-induced smooth muscle cell
      hypertrophy.
AB  - AIMS: Reactive oxygen species (ROS)-mediated intracellular signalling is well
      described in the vasculature, yet the precise roles of ROS in paracrine
      signalling are not known. Studies implicate interstitial ROS hydrogen peroxide
      (H(2)O(2)) in vascular disease, and plasma H(2)O(2) levels in the micromolar
      range are detectable in animal models and humans with hypertension. Recently,
      H(2)O(2) was shown to cross biological membranes of non-vascular cells via
      aquaporin (Aqp) water channels. Previous findings suggest that H(2)O(2) activates
      NADPH oxidase (Nox) enzymes in vascular cells and apoptosis signal-regulating
      kinase 1 (Ask1) in non-vascular cells. We hypothesized that extracellular
      H(2)O(2) induces smooth muscle cell (SMC) hypertrophy by a mechanism involving
      Aqp1, Nox1, and Ask1. METHODS AND RESULTS: Treatment of rat aortic SMCs (rASMC)
      with exogenous H(2)O(2) resulted in a concentration-dependent increase in Nox
      derived superoxide (O(2)(*-)), determined by L-012 chemiluminescence, cytochrome
      c and electron paramagnetic resonance. Nox1 was verified as the source of O(2)(.
      ) by siRNA. Aqp1 siRNA attenuated H(2)O(2) cellular entry and H(2)O(2)-induced
      O(2)(*-) production. H(2)O(2) treatment increased Ask1 activation and induced
      rASMC hypertrophy in a Nox1-dependent mechanism. Adenoviral-dominant-negative
      Ask1 attenuated H(2)O(2)-induced rASMC hypertrophy and adenoviral overexpression
      of Ask1 augmented it. CONCLUSION: Our results demonstrate for the first time that
      extracellular H(2)O(2), at pathophysiological concentrations, stimulates rASMC
      Nox1-derived O(2)(*-), subsequent Ask1 activation and SMC hypertrophy. The data
      demonstrate a novel pathway by which H(2)O(2) enters vascular cells via
      aquaporins and activates Nox, leading to hypertrophy, and provide multiple novel
      targets for combinatorial therapeutics development targeting hypertrophy and
      vascular disease.

PMID- 22997163
TI  - Exercise testing in children: comparison in ventilatory thresholds changes with
      interval-training.
AB  - The aim of this investigation was, first, to examine comparatively the changes in
      first and second ventilatory thresholds (VT1 and VT2 ) and, secondly, to compare
      with peak oxygen uptake (${?dot {?rm {V}}}_{{?rm O}_{{?rm 2}} {?rm peak}} $)
      changes following high-intensity interval training (HIT) in prepubescent
      children. Eighteen prepubescent children (aged 10.1 +/- 0.7 years) performed an
      incremental exhaustive exercise on a cycle ergometer with pulmonary gas exchange
      measurements before and after an 8-week period. During this period, nine children
      (five girls and four boys; initial ${?dot {?rm {V}}}_{{?rm O}_{{?rm 2}} {?rm
      peak}} $: 39.6 +/- 6.0 ml O2  . min(-1)  . kg(-1) ) took part in a HIT and nine
      other children (three girls and six boys; initial ${?dot {?rm {V}}}_{{?rm
      O}_{{?rm 2}} {?rm peak}} $: 39.8 +/- 7.8 ml O2  . min(-1)  . kg(-1) ), considered
      as controls, were not trained. After the training period, VT1 , VT2 , and ${?dot
      {?rm {V}}}_{{?rm O}_{{?rm 2}} {?rm peak}} $ were significantly (P < 0.01)
      improved (21%, 24%, and 14%, respectively) without significant changes in the
      control group. However, the changes in VT1 (DeltaVT1 = +4.35 +/- 4.36 ml O2  .
      min(-1)  . kg(-1) ), VT2 (DeltaVT1 = +7.17 +/- 5.17 ml O2  . min(-1)  . kg(-1) ),
      ${?dot {?rm {V}}}_{{?rm O}_{{?rm 2}} {?rm peak}} $ ($?Delta {?dot {?rm
      {V}}}_{{?rm O}_{{?rm 2}} {?rm peak}} $ = +5.51 +/- 4.17 ml O2  . min(-1)  . kg(
      1) ) induced by HIT in trained children were not related. In conclusion, for
      prepubescent children, in addition to VT1 and ${?dot {?rm {V}}}_{{?rm O}_{{?rm
      2}} {?rm peak}} $, VT2 can also be significantly improved by training. Therefore,
      HIT represents a good way to obtain great improvement in these parameters in only
      8 weeks. However, the time courses of these aerobic fitness parameters are
      dissociated, which implies the need to differentiate among them during aerobic
      fitness exercise testing.

PMID- 22997164
TI  - Physical plugging does not account for attenuation of capillary leakage by
      hydroxyethyl starch 130/0.4: a synthetic gel layer model.
AB  - Hydroxyethyl starch (HES) solutions, widely used plasma substitutes, reportedly
      attenuate capillary leakage via physical plugging of capillary defects. We
      investigated how 2% HES solutions of different molecular weights (HES(70): 70
      kDa, HES(130): 130 kDa, HES(200): 200 kDa, and HES(670): 670 kDa) affect dye
      release from polyacrylamide gels (PAGs) as a model of endothelial glycocalyx. We
      assessed dye release from 4% PAG with varying concentrations of albumin [0, 1, 2,
      4, and 8% (w/v)] by measuring the change in dye absorbance (DeltaAbs) at 5 h for
      each HES solution. For PAG containing no albumin, DeltaAbs for HES(130) was 30%
      lower than that for HES(70) and HES(200), and 50% lower than that for HES(670).
      At concentrations of 1-8% albumin, DeltaAbs at 5 h with HES(70), HES(130), and
      HES(200) solutions were almost half that with the HES(670) solution, but no
      significant differences were noted in DeltaAbs at 5 h among HES(70), HES(130),
      and HES(200) solutions. The inhibition of dye release by HES(670) is likely due
      to the hindering effect of HES molecules partitioned into gel pores. However, a
      unique property of HES(130) , including the heavy hydroxyethylation at the C(2)
      position, may promote specific interactions with PAG and thereby inhibit solute
      release.

PMID- 22997165
TI  - Determination of phenoxy herbicides in water samples using phase transfer
      microextraction with simultaneous derivatization followed by GC-MS analysis.
AB  - A sensitive and accurate method for the determination of two model phenoxy
      herbicides, 4-chloro-2-methylphenoxy acetic acid and 4-chloro-2-methylphenoxy
      propanoic acid, in water is explained. This method utilizes a simple phase
      transfer catalyst-assisted microextraction with simultaneous derivatization.
      Factors affecting the performance of this method including pH of the aqueous
      matrix, temperature, extraction duration, type and amount of derivatization
      reagents, and type and amount of the phase transfer catalyst are examined.
      Derivatization and the use of phase transfer catalyst have proven to be
      especially vital for the resolution of the analytes and their sensitive
      determination, with an enrichment factor of 288-fold for catalyzed over
      noncatalyzed procedure. Good linearity ranging from 0.1 to 80 MUg L(-1)  with
      correlation of determination (r(2) ) between 0.9890 and 0.9945 were obtained.
      Previous reported detection limits are compared with our new current method. The
      low LOD for the two analytes (0.80 ng L(-1)  for 4-chloro-2-methylphenoxy
      propanoic acid and 3.04 ng L(-1)  for 4-chloro-2-methylphenoxy acetic acid) allow
      for the determination of low concentrations of these analytes in real samples.
      The absence of matrix effect was confirmed through relative recovery
      calculations. Application of the method to seawater and tap water samples was
      tested, but only 4-chloro-2-methylphenoxy propanoic acid at concentrations
      between 0.27 +/- 0.01 and 0.84 +/- 0.06 MUg L(-1)  was detected in seawater
      samples.

PMID- 22997166
TI  - The Kety-Schmidt technique for quantitative perfusion and oxygen metabolism
      measurements in the MR imaging environment.
AB  - SUMMARY: The Kety-Schmidt technique provides quantitative measurement of whole
      brain CBF. CBF is measured as the area between the arterial and venous washout
      curves of a diffusible tracer. Oxygen extraction and metabolism may be calculated
      from arterial and venous samples. In this report, we present a method for
      performing these measurements in an MR imaging environment. This technique could
      be useful for validation of MR imaging methods of hemodynamic and metabolic
      measurements in humans.

PMID- 22997167
TI  - Prediction of nodal metastasis in head and neck cancer using a 3T MRI ADC map.
AB  - BACKGROUND AND PURPOSE: The detection of cervical nodal metastases is important
      for the prognosis and treatment of head and neck tumors. The purpose of this
      study was to assess the ability of ADC values at 3T to distinguish malignant from
      benign lymph nodes. MATERIALS AND METHODS: From July 2009 to June 2010, twenty
      two patients (21 men and 1 woman; mean age, 49.8+/-9.5 years; age range, 28-66
      years) scheduled for surgical treatment of biopsy-proved head and neck cancer
      were prospectively and consecutively enrolled in this study. All patients were
      scanned on a 3T imaging unit (Verio) by using a 12-channel head coil combined
      with a 4-channel neck coil. Histologic findings were the reference standard for
      the diagnosis of lymph node metastasis. RESULTS: The ADC values derived from the
      signal intensity averaged across images obtained with b-values of 0 and 800 s/mm2
      were 1.086+/-0.222*10(-3) mm2/s for benign lymph nodes and 0.705+/-0.118*10(-3)
      mm2/s for malignant lymph nodes (P<.0001). When an ADC value of 0.851*10(-3)
      mm2/s was used as a threshold value for differentiating benign from malignant
      lymph nodes, the best results were obtained with an accuracy of 91.0%,
      sensitivity of 91.3%, and specificity of 91.1%. CONCLUSIONS: The ADC value is a
      sensitive and specific parameter that can help to differentiate malignant from
      benign lymph nodes.

PMID- 22997168
TI  - Probabilistic radiographic atlas of glioblastoma phenotypes.
AB  - BACKGROUND AND PURPOSE: Tumor location is a significant prognostic factor in
      glioblastoma, which may reflect the genetic profile of tumor precursor cells. The
      purpose of the current study was to construct and analyze probabilistic
      radiographic atlases reflecting preoperative tumor locations and corresponding
      demographic, "-omic," and interventional phenotypes to provide insight into
      potential niche locations of glioblastoma cells of origin. MATERIALS AND METHODS:
      Preoperative anatomic MR images in 507 patients with de novo glioblastoma were
      analyzed. Images were registered to stereotactic space, tumors were segmented,
      and the stereospecific frequency of tumor occurrence was analyzed statistically
      by age, extent of resection, MGMT methylation, IDH1 mutation, gene expression
      subclassification, PTEN loss, PTEN deficiency, EGFR amplification, EGFR variant 3
      expression, progression-free survival from the start of radiochemotherapy, and
      overall survival from initial diagnosis. RESULTS: Most glioblastomas grow into
      the periventricular white matter regions adjacent to the subventricular zone.
      MGMT promoter methylated tumors occur more frequently in the left temporal lobe,
      in young patients with glioblastoma, in IDH1 mutant tumors, in tumors having the
      proneural gene expression subtype, and in tumors lacking loss of PTEN occurring
      most frequently in the frontal lobe. MGMT methylated tumors with the IDH1
      mutation tended to occur in the left frontal lobe. EGFR amplified and EGFR
      variant 3-expressing tumors occurred most frequently in the left temporal lobe. A
      similar region in the left temporal lobe was associated with favorable response
      to radiochemotherapy and increased survival. CONCLUSIONS: Radiographic atlases
      for specific phenotypes provide insight into overlap between prognostic variables
      and may help to identify niche locations for cancer cells of origin.

PMID- 22997169
TI  - Enhanced photocurrent in thin-film amorphous silicon solar cells via shape
      controlled three-dimensional nanostructures.
AB  - In this paper, we have explored manufacturable approaches to  sub-wavelength
      controlled three-dimensional (3D) nano-patterns with the goal of significantly
      enhancing the photocurrent in amorphous silicon solar cells. Here we demonstrate
      efficiency enhancement of about 50% over typical flat a-Si thin-film solar cells,
      and report an enhancement of 20% in optical absorption over Asahi textured glass
      by fabricating sub-wavelength nano-patterned a-Si on glass substrates. External
      quantum efficiency showed superior results for the 3D nano-patterned thin-film
      solar cells due to enhancement of broadband optical absorption. The results
      further indicate that this enhanced light trapping is achieved with minimal
      parasitic absorption losses in the deposited transparent conductive oxide for the
      nano-patterned substrate thin-film amorphous silicon solar cell configuration.
      Optical simulations are in good agreement with experimental results, and also
      show a significant enhancement in optical absorption, quantum efficiency and
      photocurrent.

PMID- 22997170
TI  - Long-term outcomes of Group D eyes in bilateral retinoblastoma patients treated
      with chemoreduction and low-dose IMRT salvage.
AB  - BACKGROUND: To evaluate outcomes of Group D eyes of bilateral retinoblastoma
      patients treated with primary chemoreduction and external beam radiation as
      salvage. PROCEDURE: Retrospective chart review of patients diagnosed with
      bilateral retinoblastoma and designated Group D in at least one eye from January
      1, 2000 to December 31, 2009. Overall, 62 Group D eyes of 49 patients were
      included; 13 had bilateral Group D disease. Primary chemoreduction with
      vincristine, etoposide, and carboplatin with local consolidation was
      administered, followed by external beam radiation in the form of intensity
      modulated radiation therapy (IMRT) as salvage for recurrent tumor. Primary
      outcome measure was globe salvage. RESULTS: Of 62 Group D eyes, 7 were enucleated
      primarily; 55 were treated with systemic chemoreduction, and local therapy.
      Chemoreduction cured 26 of 55 eyes (47%). Recurrences were found in 29 eyes; 5
      underwent enucleation and 24 were treated with IMRT at a dose of 24 Gy (2 eyes)
      or 36 Gy (22 eyes). Of the 24 irradiated eyes, 19 (79%) were salvaged and 5
      required enucleation. Final visual acuity ranged from 20/20 to light perception
      with 10 eyes having 20/80 or better visual acuity. Average follow-up was 54.2
      months. CONCLUSION: Kaplan-Meier estimates of eye survival of Group D eyes in
      bilateral patients at 12 months is 82% (95% confidence interval [CI] 70.1-89.7%);
      at 60 months eye survival is estimated to be 68% (95% confidence interval [CI]
      55.4-82.8%). Systemic treatment for retinoblastoma demonstrated a high rate of
      globe preservation with acceptable complications and many eyes retaining
      functional vision.

PMID- 22997171
TI  - A facile synthesis of novel bis-(indolyl)-1,3,4-oxadiazoles as potent cytotoxic
      agents.
AB  - A recipe for potency: A novel series of bis(indolyl)-1,3,4-oxadiazoles was
      prepared from the corresponding hydrazide-hydrazones via iodobenzene diacetate
      promoted oxidative cyclization. Evaluation against a panel of human cancer cell
      lines revealed that some derivatives possess potent cytotoxicity with tunable
      selectivity for different cancer types. 

PMID- 22997172
TI  - Preliminary investigation of crosslinked chitosan sponges for tailorable drug
      delivery and infection control.
AB  - Local versus systemic antibiotic delivery may be an effective strategy for
      treating musculoskeletal infections, especially when antibiotic-resistant
      bacteria are present. Lyophilized uncrosslinked, genipin crosslinked, and genipin
      crosslinked with poly(N-isopropylacrylamide) (PNIPAM) chitosan sponges were
      analyzed for their in vitro degradation rate, chemical crosslinking, antibiotic
      uptake, elution, biologic activity, and cytotoxicity. These evaluations were
      pursued to determine if crosslinking with genipin could be used to create a
      tailorable point of care loaded sponge for local infection control. Crosslinking
      the chitosan sponges decreased degradation in phosphate-buffered saline from 4.48
      +/- 2.28 wt % remaining of the uncrosslinked sponges to 78.82 +/- 1.15 and 73.87
      +/- 1.27 wt % remaining at week 1 for the genipin and PNIPAM/genipin crosslinked
      sponges, respectively. The PNIPAM/genipin crosslinked sponges exhibited the most
      sustained release of biologically active antibiotics, with an average antibiotic
      release 63% higher than uncrosslinked and 37% higher than genipin crosslinked
      sponges, after 96 h. No significant cytotoxic effects from sponges or eluates
      were exhibited with NIH 3T3 fibroblasts. These preliminary results indicate that
      genipin crosslinked chitosan sponges, with or without PNIPAM, have potential as
      local delivery systems for adjunctive therapy for infection control, especially
      when longer degradation periods and higher antibiotic elutions are desired.

PMID- 22997173
TI  - Hemoptysis from bronchial varices associated with pulmonary vein stenosis: role
      of surgical repair.
AB  - We present the case of a 6-year-old child who presented with an episode of life
      threatening hemoptysis. Investigations revealed multiple areas of endobronchial
      varices and abnormal pleural vessels as well as severe left pulmonary vein
      stenosis and an atrial septal defect (ASD). After extensive work up and
      consultation he underwent repair of the left pulmonary vein using a sutureless
      technique and ASD closure. This resulted in a marked improvement in the
      appearances of the left lung. The bronchial varices in the right lung remain
      unchanged. No further hemoptysis has occurred and the child continues to be
      monitored.

PMID- 22997175
TI  - Quantum dot PbS(0.9)Se(0.1)/TiO2 heterojunction solar cells.
AB  - We report on photovoltaic cells based on ternary PbS(0.9)Se(0.1) quantum dots
      utilizing a heterojunction type device configuration. The best device shows an AM
      1.5 power conversion efficiency of 4.25%. Furthermore, this ternary PbS(x)Se(1-x)
      quantum dot heterojunction device has a peak external quantum efficiency above
      100% at 2.76 eV, approximately 2.7* the bandgap energy. The ternary quantum dots
      combine the higher short circuit currents of the binary PbSe system with the
      higher open circuit voltages of the binary PbS system.

PMID- 22997176
TI  - Nutritional status of children and young adults with Ewing sarcoma or
      osteosarcoma at diagnosis and during multimodality therapy.

PMID- 22997174
TI  - Homeostatic control of synaptic activity by endogenous adenosine is mediated by
      adenosine kinase.
AB  - Extracellular adenosine, a key regulator of neuronal excitability, is metabolized
      by astrocyte-based enzyme adenosine kinase (ADK). We hypothesized that ADK might
      be an upstream regulator of adenosine-based homeostatic brain functions by
      simultaneously affecting several downstream pathways. We therefore studied the
      relationship between ADK expression, levels of extracellular adenosine, synaptic
      transmission, intrinsic excitability, and brain-derived neurotrophic factor
      (BDNF)-dependent synaptic actions in transgenic mice underexpressing or
      overexpressing ADK. We demonstrate that ADK: 1) Critically influences the basal
      tone of adenosine, evaluated by microelectrode adenosine biosensors, and its
      release following stimulation; 2) determines the degree of tonic adenosine
      dependent synaptic inhibition, which correlates with differential plasticity at
      hippocampal synapses with low release probability; 3) modulates the age-dependent
      effects of BDNF on hippocampal synaptic transmission, an action dependent upon co
      activation of adenosine A2A receptors; and 4) influences GABAA receptor-mediated
      currents in CA3 pyramidal neurons. We conclude that ADK provides important
      upstream regulation of adenosine-based homeostatic function of the brain and that
      this mechanism is necessary and permissive to synaptic actions of adenosine
      acting on multiple pathways. These mechanistic studies support previous
      therapeutic studies and implicate ADK as a promising therapeutic target for
      upstream control of multiple neuronal signaling pathways crucial for a variety of
      neurological disorders. 

PMID- 22997177
TI  - Luminescent benzoquinolate-isocyanide platinum(II) complexes: effect of Pt???Pt
      and pi???pi interactions on their photophysical properties.
AB  - The neutral compounds [Pt(bzq)(CN)(CNR)] (R = tBu (1), Xyl (2), 2-Np (3); bzq =
      benzoquinolate, Xyl = 2,6-dimethylphenyl, 2-Np = 2-napthyl) were isolated as the
      pure isomers with a trans-C(bzq),CNR configuration, as confirmed by (13)C{(1)H}
      NMR spectroscopy in the isotopically marked [Pt(bzq)((13)CN)(CNR)] (R = tBu (1'),
      Xyl (2'), 2-Np (3')) derivatives (delta(13)C(CN) ~ 110 ppm; (1) J(Pt,(13)C) ~
      1425 Hz]. By contrast, complex [Pt(bzq)(C=CPh)(CNXyl)] (4) with a trans
      N(bzq),CNR configuration, has been selectively isolated from [Pt(bzq)Cl(CNXyl)]
      (trans-N(bzq),CNR) using Sonogashira conditions. X-ray diffraction studies reveal
      that while 1 adopts a columnar-stacked chain structure with Pt-Pt distances of
      3.371(1) A and significant pi???pi interactions (3.262 A), complex 2 forms dimers
      supported only by short Pt???Pt (3.370(1) A) interactions. In complex 4 the
      packing is directed by weak bzq???Xyl and bzq???C=E (C, N) interactions. In solid
      state at room temperature, compounds 1 and 2 both show a bright red emission (phi
      = 42.1% 1, 57.6% 2). Luminescence properties in the solid state at 77 K and
      concentration-dependent emission studies in CH(2)Cl(2) at 298 K and at 77 K are
      also reported for 1-4.

PMID- 22997178
TI  - Respiratory health outcomes 1 year after admission with severe lower respiratory
      tract infection.
AB  - Severe lower respiratory infection (LRI) is believed to be one precursor of
      protracted bacterial bronchitis, chronic moist cough (CMC), and chronic
      suppurative lung disease. The aim of this study was to determine and to describe
      the presence of respiratory morbidity in young children 1 year after being
      hospitalized with a severe LRI. Children aged less than 2 years admitted from
      August 1, 2007 to December 23, 2007 already enrolled in a prospective
      epidemiology study (n = 394) were included in this second study only if they had
      a diagnosis of severe bronchiolitis or of pneumonia with no co-morbidities (n =
      237). Funding allowed 164 to be identified chronologically, 131 were able to be
      contacted, and 94 agreed to be assessed by a paediatrician 1 year post index
      admission. Demographic information, medical history and a respiratory
      questionnaire was recorded, examination, pulse oximetry, and chest X-ray (CXR)
      were performed. The predetermined primary endpoints were; (i) history of CMC for
      at least 3 months, (ii) the presence of moist cough and/or crackles on
      examination in clinic, and (iii) an abnormal CXR when seen at a time of
      stability. Each CXR was read by two pediatric radiologists blind to the
      individuals' current health. Results showed 30% had a history of CMC, 32% had a
      moist cough and/or crackles on examination in clinic, and in 62% of those with a
      CXR it was abnormal. Of the 81 children with a readable follow-up X-ray, 11% had
      all three abnormal outcomes, and 74% had one or more abnormal outcomes. Three
      children had developed bronchiectasis on HRCT. The majority of children with a
      hospital admission at <2 years of age for severe bronchiolitis or pneumonia
      continued to have respiratory morbidity 1 year later when seen at a time of
      stability, with a small number already having sustained significant lung disease.

PMID- 22997179
TI  - Influence of annealing conditions on the formation of regular lattices of voids
      and Ge quantum dots in an amorphous alumina matrix.
AB  - In this work, the influence of air pressure during the annealing of Ge quantum
      dot (QD) lattices embedded in an amorphous Al(2)O(3) matrix on the structural,
      morphological and compositional properties of the film is studied. The formation
      of a regularly ordered void lattice after performing a thermal annealing process
      is explored. Our results show that both the Ge desorption from the film and the
      regular ordering of the QDs are very sensitive to the annealing parameters. The
      conditions for the formation of a void lattice, a crystalline Ge QD lattice and a
      disordered QD lattice are presented. The observed effects are explained in terms
      of oxygen interaction with the Ge present in the film.

PMID- 22997180
TI  - Further evidence for the co-occurrence of adverse health behaviors among
      childhood cancer survivors.

PMID- 22997181
TI  - An efficient approach for the construction of benzazepine and benzoxepine
      derivatives.
AB  - A novel and facile synthetic protocol for the construction of benzazepine and
      benzoxepine derivatives through a copper(I)-catalyzed reaction of 2-(2
      ethynylphenyl)-1-tosylaziridine or 2-(2-ethynylphenyl)oxirane with sulfonyl
      azides is disclosed. A ketenimine is the key intermediate during the reaction
      process.

PMID- 22997182
TI  - Horizontal gene transfer in choanoflagellates.
AB  - Horizontal gene transfer (HGT), also known as lateral gene transfer, results in
      the rapid acquisition of genes from another organism. HGT has long been known to
      be a driving force in speciation in prokaryotes, and there is evidence for HGT
      from symbiotic and infectious bacteria to metazoans, as well as from protists to
      bacteria. Recently, it has become clear that as many as a 1,000 genes in the
      genome of the choanoflagellate Monosiga brevicollis may have been acquired by
      HGT. Interestingly, these genes reportedly come from algae, bacteria, and other
      choanoflagellate prey. Some of these genes appear to have allowed an ancestral
      choanoflagellate to exploit nutrient-poor environments and were not passed on to
      metazoan descendents. However, some of these genes are also found in animal
      genomes, suggesting that HGT into a common ancestor of choanozoans and animals
      may have contributed to metazoan evolution.

PMID- 22997183
TI  - Trimming long-term tunneled central venous catheters in pediatric patients.
AB  - Long-term tunneled central venous catheters (CVC) are employed in critically ill
      patients. Manufacturers do not provide patient-customized devices; therefore,
      trimming is required for pediatric use. Scanning Electron Microscopy (SEM)
      coupled with energy-dispersive X-ray spectroscopy and attenuated total reflection
      Fourier transform infrared spectroscopy (ATR-FTIR) was used to assess changes
      induced by different trimming methods on single and double lumen Hickman-Broviac
      catheters. Increased roughness, exposure of inorganic macroaggreagates and
      increase in surface inorganic charges were generated by the trimming procedure,
      with the scalpel producing a smoother surface compared to scissors. Trimming
      produces changes on the CVC surface that may influence the rate of long-term
      complications.

PMID- 22997184
TI  - The unprecedented tetrakis-(disulfato)-silicate anion [Si(S2O7)4]4-, its
      germanium congener [Ge(S2O7)4]4-, and the tris-(disulfato)-metallates [M(S2O7)3]2
      (M = Si, Ge, Ti), stabilized by divalent counter cations B2+ (B = Sr, Ba, Pb).
AB  - The reaction of oleum (65% SO(3)) with the tetrachlorides of silicon, germanium,
      and titanium, respectively, led to the complex disulfates Sr(2)[M(S(2)O(7))(4)]
      (M = Si, Ge), Ba[M(S(2)O(7))(3)] (M = Si, Ge, Ti) and Pb[M(S(2)O(7))(3)] (M = Ge,
      Ti) if strontium, barium, and lead were used as divalent counter cations. The
      strontium compounds exhibit the unique tetrakis-(disulfato)-metallate anions
      [M(S(2)O(7))(4)](4-) with the silicon and germanium atoms in octahedral
      coordination of two chelating and two monodentate disulfate groups. All of the
      other compounds display tris-(disulfato)-metallate anions [M(S(2)O(7))(3)](2-)
      with three chelating disulfate groups surrounding the M atoms. Thermoanalytical
      investigations on the germanium compounds Sr(2)[Ge(S(2)O(7))(4)] and
      Ba[Ge(S(2)O(7))(3)] revealed their decomposition in multi-step processes leading
      to a mixture of BSO(4) and BGe(4)O(9) (B = Sr, Ba), while the thermal degradation
      of Pb[Ti(S(2)O(7))(3)] yields PbTiO(3). For selected examples, IR data are
      additionally presented.

PMID- 22997185
TI  - High fat food increases gastric residence and thus thresholds for objective
      symptoms in allergic patients.
AB  - SCOPE: We have tested the hypothesis that high fat foods such as chocolate induce
      reduced rates of gastric emptying in comparison to lower fat foods and that this
      can impact uptake of allergens and subsequent reactions in allergic patients.
      METHODS AND RESULTS: In four volunteers, magnetic resonance imaging was used to
      measure gastric emptying of a series of nine doses of either dark chocolate bars
      containing 35% fat or a chocolate dessert containing 8% fat. Analysis showed a
      mean rate of decrease in gastric volume with an 8% fat dessert was 0.33 +/- 0.09
      mL/min compared to an average rate of increase in gastric volume of 0.09 +/- 0.10
      mL/min for the chocolate bars. In parallel, eight allergic patients were
      challenged for either peanut or hazelnut in the same two matrices and doses using
      a standardized protocol. A statistical analysis of the objective symptoms in the
      allergic patients showed that the chocolate bars gave a significantly higher
      threshold for objective symptoms than the dessert. CONCLUSIONS: Chocolate bars
      induced lower gastric emptying rates and in food challenges with allergic
      patients gave a higher threshold of elicitation for objective reactions than a
      dessert.

PMID- 22997186
TI  - Increased adherence to CFF practice guidelines for pulmonary medications
      correlates with improved FEV1.
AB  - BACKGROUND: CFF practice guidelines recommend patients >=age 6 use dornase alfa
      and hypertonic saline daily, and those >=age 6 colonized with Pseudomonas
      aeruginosa use inhaled tobramycin and oral azithromycin to improve lung function
      and reduce pulmonary exacerbations. A decline in FEV1 was noted in our 2008 CF
      Center Report. We hypothesized that increasing adherence to prescribing
      guidelines for these pulmonary medications would improve mean FEV1. METHODS: This
      was a quality improvement project completed at a US CF center. CFF practice
      guidelines were reviewed with the center physicians. Patients were identified
      that were eligible to receive recommended therapies and it was determined whether
      they were prescribed the therapies. Baseline FEV1 data was collected. Adherence
      rates and FEV1 were followed quarterly for 1 year. Providers received a quarterly
      report card with adherence rates, mean FEV1 compared to colleagues, and a list of
      eligible patients that were not prescribed recommended therapies. RESULTS: Ninety
      two patients were included. At baseline, the overall adherence rate was 59%.
      Overall adherence increased quarterly (P = < 0.001). Each quarter there was
      improvement in adherence to prescribing for each medication (P < 0.001). Except
      in quarter 1, FEV1 increased quarterly (P = 0.092). There was moderate
      correlation (r = 0.533) between improved adherence and improved FEV1.
      CONCLUSIONS: Educating clinicians about guidelines, providing feedback on
      adherence to guidelines, and monitoring prescribing patterns improves prescribing
      adherence. FEV1 showed improvement after months of sustained adherence, trending
      towards significance. Longer follow-up is necessary to determine if improved
      prescribing adherence translates into improved FEV1 or slows rate of decline in
      FEV1.

PMID- 22997187
TI  - Cardiovascular health informatics: risk screening and intervention.
AB  - Despite enormous efforts to prevent cardiovascular disease (CVD) in the past, it
      remains the leading cause of death in most countries worldwide. Around two-thirds
      of these deaths are due to acute events, which frequently occur suddenly and are
      often fatal before medical care can be given. New strategies for screening and
      early intervening CVD, in addition to the conventional methods, are therefore
      needed in order to provide personalized and pervasive healthcare. In this special
      issue, selected emerging technologies in health informatics for screening and
      intervening CVDs are reported. These papers include reviews or original
      contributions on 1) new potential genetic biomarkers for screening CVD outcomes
      and high-throughput techniques for mining genomic data; 2) new imaging techniques
      for obtaining faster and higher resolution images of cardiovascular imaging
      biomarkers such as the cardiac chambers and atherosclerotic plaques in coronary
      arteries, as well as possible automatic segmentation, identification, or fusion
      algorithms; 3) new physiological biomarkers and novel wearable and home
      healthcare technologies for monitoring them in daily lives; 4) new personalized
      prediction models of plaque formation and progression or CVD outcomes; and 5)
      quantifiable indices and wearable systems to measure them for early intervention
      of CVD through lifestyle changes. It is hoped that the proposed technologies and
      systems covered in this special issue can result in improved CVD management and
      treatment at the point of need, offering a better quality of life to the patient.

PMID- 22997188
TI  - Posture recognition based on fuzzy logic for home monitoring of the elderly.
AB  - We propose in this paper a computer vision-based posture recognition method for
      home monitoring of the elderly. The proposed system performs human detection
      prior to the posture analysis; posture recognition is performed only on a human
      silhouette. The human detection approach has been designed to be robust to
      different environmental stimuli. Thus, posture is analyzed with simple and
      efficient features that are not designed to manage constraints related to the
      environment but only designed to describe human silhouettes. The posture
      recognition method, based on fuzzy logic, identifies four static postures and is
      robust to variation in the distance between the camera and the person, and to the
      person's morphology. With an accuracy of 74.29% of satisfactory posture
      recognition, this approach can detect emergency situations such as a fall within
      a health smart home.

PMID- 22997189
TI  - Mesh-bone cement sandwich for sternal and sternoclavicular joint reconstruction.
AB  - Resection of the manubrium including both sternoclavicular joints is occasionally
      performed in the case of sternal tumours. Sternoclavicular joints are the only
      true joints connecting the axial skeleton to the upper extremity. Therefore, they
      play an important role in shoulder function. However, data on their
      reconstruction are lacking. Here, we described the case of a sternal
      reconstruction including both sternoclavicular joints using a mesh-bone cement
      sandwich. The mechanical properties of the construct mimicked those of the
      original sternoclavicular joints and could therefore restore shoulder strength
      allowing the patient to perform overhead work.

PMID- 22997190
TI  - Successful transmitral repair of an inferobasal postinfarct pseudoaneurysm.

PMID- 22997191
TI  - Prognostic value of B-type natriuretic peptide in patients with chronic mitral
      regurgitation undergoing surgery: mid-term follow-up results.
AB  - OBJECTIVES: The prognostic value of B-type natriuretic peptide (BNP) for surgical
      outcome in patients with mitral regurgitation (MR) has not been studied. The
      purpose of this study was to determine the prognostic value of BNP in patients
      with chronic severe MR, undergoing mitral valve surgery. METHODS: In total, 117
      patients with chronic severe MR undergoing surgery were evaluated from the MR
      registry of Seoul National University Hospital. Patients were excluded if they
      had acute MR or acutely decompensated heart failure, and significant renal,
      pulmonary, coronary or other significant valvular heart disease. The plasma BNP
      level assay and echocardiographic studies were done before surgery. Study
      endpoint was a composite of cardiac death and cardiac hospitalization during
      follow-up. RESULTS: The median duration of the follow-up was 4.5 years, and the
      study endpoint was reached in 11 (9.4%) patients. Receiver-operating
      characteristic curve analysis yielded an optimal cut-off point of 125 pg/ml for
      BNP that distinguished patients with poor prognosis. Kaplan-Meier survival
      analysis with the log-rank test and multivariate Cox proportional hazards model
      showed that patients with BNP >=125 pg/ml had a worse clinical outcome after
      surgery (log rank 7.606, P = 0.006; adjusted hazard ratio = 5.536 [95% confidence
      interval 1.189-25.788], P = 0.029). CONCLUSIONS: Among patients with chronic
      severe MR undergoing mitral valve surgery, BNP independently predicts the poor
      clinical outcome. The BNP measurement should be considered in the risk
      stratification of these patients.

PMID- 22997192
TI  - Two cases of localized neuroblastoma with multiple segmental chromosomal
      alterations and metastatic progression.
AB  - Surgery alone is curative for most children with localized MYCN-non-amplified
      neuroblastoma. However, 10-15% will develop recurrent loco-regional disease, and
      very rarely, patients will relapse metastatically. Currently, it is not possible
      to predict which child with localized, MYCN-non-amplified neuroblastoma will
      develop disseminated disease. We report two children who presented with favorable
      biology, localized neuroblastoma and subsequently relapsed with metastatic
      disease after treatment with surgery. Whole-genome DNA copy number analyses
      performed on the diagnostic tumors identified 15 (case 1) and 8 (case 2)
      segmental chromosomal alterations. Further analysis of the prognostic value of
      whole-genome analysis in children with localized neuroblastoma is warranted.

PMID- 22997193
TI  - Asymmetric organocatalytic addition reactions of maleimides: a promising approach
      towards the synthesis of chiral succinimide derivatives.
AB  - Recent progress in asymmetric organocatalysis has led to the development of
      several asymmetric transformations that employ various substrates. Among these
      substrates, maleimides have emerged as excellent Michael acceptors, dienophiles,
      and dipolarophiles. In this Focus Review we highlight the advances in the
      asymmetric synthesis of succinimide derivatives through asymmetric
      organocatalytic addition reactions of maleimides.

PMID- 22997194
TI  - Lower airway anomalies in children with CATCH 22 syndrome and congenital heart
      disease.
AB  - OBJECTIVE: CATCH 22 syndrome is a medical acronym for multiple abnormalities,
      especially cardiac defect. The patients with congenital heart disease (CHD)
      usually have more complicated post-surgery course. METHODS: We reviewed 4-year
      experience in our hospital to define the lower airway anomalies and the clinical
      implications in patients with CATCH 22 syndrome and CHD. From 2004 to 2007, 18
      patients who underwent computed tomography for planning of cardiovascular
      treatment were enrolled. Detection of airway anomalies were performed on computed
      tomography. RESULTS: Characteristic dysmorphic facial features were noted in 8
      out of 18 patients (44%). Ten patients (55.6%) had mild to moderate tracheal or
      bronchial stenosis. Five patients (28%) had tracheomalacia or bronchomalacia.
      Comparing to control group, patients received the first major surgery with a
      median hospital stays of 42 days in study group had a significantly longer
      hospital stay (42 vs. 16, P = 0.005) and longer duration of ventilator usage (16
      vs. 4, P = 0.014). The difference of the mean position of the carina on computed
      tomography image between study groups and control groups was about three-quarters
      of a vertebral body height (P < 0.05). CONCLUSIONS: Patients with CATCH 22
      syndrome and CHD had a shorter length of trachea compared to that of the age
      matched similar CHD. The incidence of associated lower airway anomalies in CHD
      children with CATCH 22 syndrome was higher. It may lead to longer time of
      ventilator support after surgery as well as total hospital stays than those of
      CHD without CATCH 22 syndrome.

PMID- 22997195
TI  - Trypsin impaired epithelial barrier function and induced IL-8 secretion through
      basolateral PAR-2: a lesson from a stratified squamous epithelial model.
AB  - Immune-mediated injury by the protease-activated receptor-2-interleukin-8 (PAR-2
      IL8) pathway may underlie the development of gastroesophageal reflux disease
      (GERD). However, the localization of PAR-2 and the mechanism of PAR-2 activation
      remain unclear. This study aimed to address these questions on an esophageal
      stratified squamous epithelial model and in the human esophageal mucosa of GERD
      patients. Normal human esophageal epithelial cells were cultured with the air
      liquid interface system to establish the model. SLIGKV-NH2 (PAR-2 synthetic
      agonist), trypsin (PAR-2 natural activator), and weak acid (pH 4, 5, and 6) were
      added to either the apical or basolateral compartment to evaluate their effects
      on transepithelial electrical resistance (TEER) and IL-8 production. PAR-2
      localization was examined both in the cell model and biopsies from GERD patients
      by immunohistochemistry. Apical trypsin stimulation induced IL-8 accompanied by
      decreased TEER in vitro, whereas the effective concentration from the basolateral
      side was 10 times lower. SLIGKV-NH2 from basolateral but not apical stimulation
      induced IL-8 production. Apical weak acid stimulation did not influence TEER or
      IL-8 production. Immunohistochemistry showed intense reactivity of PAR-2 in the
      basal and suprabasal layers after stimulation with trypsin. A similar PAR-2
      reactivity that was mainly located at the basal and suprabasal layers was
      detected in GERD patients. In conclusion, the activation of the PAR-2-IL-8
      pathway probably occurred at the basal and suprabasal layers, while the
      esophageal epithelial barrier may influence the activation of PAR-2. Under proton
      pump inhibitor therapy, refluxed trypsin may remain active and be a potential
      agent in the pathogenesis of refractory GERD.

PMID- 22997196
TI  - Colitis is associated with a loss of intestinofugal neurons.
AB  - Intestinofugal neurons sense and receive information regarding mechanical
      distension of the bowel and transmit this information to postganglionic
      sympathetic neurons in the prevertebral ganglia. Previous studies have
      demonstrated that trinitrobenzene sulfonic acid (TNBS)-induced colitis is
      associated with a loss of myenteric neurons that occurs within the first 12 h
      following the inflammatory insult. The purpose of this study was to test the
      hypothesis that intestinofugal neurons are among the myenteric neurons lost
      during TNBS-induced colitis. The retrograde tracing dye Fast Blue was used to
      label intestinofugal neurons, and immunohistochemical staining for the RNA
      binding proteins HuC/D was used to count all myenteric neurons. Ongoing synaptic
      input to neurons in the guinea pig inferior mesenteric ganglion (IMG) was
      recorded via conventional intracellular electrophysiology. In control
      preparations, intestinofugal neurons account for 0.25% of myenteric neurons. In
      the distal colon of TNBS-treated animals, the proportion of intestinofugal
      neurons was reduced to 0.05% (an 80% reduction) within the region of inflammation
      where 20-25% of myenteric neurons were lost. Neither intestinofugal neurons
      specifically nor myenteric neurons were reduced in more proximal uninflamed
      regions. There is a reduction in the frequency of ongoing synaptic potentials in
      visceromotor neurons of the IMG at 12 and 24 h and 6 and 56 days after TNBS.
      Collectively, the results of this study suggest that intestinofugal neurons are
      among the myenteric neurons lost during inflammation and may be selectively
      targeted. Because intestinofugal neurons are a major driver of sympathetic output
      to the gut, the loss of intestinofugal neurons may have a profound
      pathophysiological significance.

PMID- 22997197
TI  - Influence of defunctionalization and mechanical forces on intestinal epithelial
      wound healing.
AB  - The influence on mucosal healing of luminal nutrient flow and the forces it
      creates are poorly understood. We hypothesized that altered deformation and
      extracellular pressure mediate, in part, the effects of defunctionalization on
      mucosal healing. We created patent or partially obstructing defunctionalizing
      jejunal Roux-en-Y anastomoses in rats to investigate mucosal healing in the
      absence or presence of luminal nutrient flow and measured luminal pressures to
      document partial obstruction. We used serosal acetic acid to induce ulcers in the
      proximal, distal, and defunctionalized intestinal segments. After 3 days, we
      assessed ulcer area, proliferation, and phosphorylated ERK. In vitro, we measured
      proliferation and migration in Caco-2 and IEC-6 intestinal epithelial cells
      subjected to cyclic strain, increased extracellular pressure, or strain and
      pressure together. Defunctionalization of intestine without obstruction reduced
      phosphorylated ERK, slowed ulcer healing, and inhibited mucosal proliferation.
      This outcome was blocked by PD-98059. Partial obstruction delayed ulcer healing
      but stimulated proliferation independently of ERK. In vitro, strain increased
      Caco-2 and IEC-6 proliferation and reduced migration across collagen but reduced
      proliferation and increased migration across fibronectin. In contrast, increased
      pressure and the combination of pressure and strain increased proliferation and
      reduced migration independently of substrate. PD-98059 reduced basal migration
      but increased migration under pressure. These results suggest that loss of the
      repetitive distension may decrease mucosal healing in defunctionalized bowel,
      while increased luminal pressure above anastomoses or in spastic bowel disease
      could further inhibit mucosal healing, despite peristaltic repetitive strain. ERK
      may mediate the effects of repetitive deformation but not the effects of
      pressure.

PMID- 22997199
TI  - Heterogeneity in histone 2B-green fluorescent protein-retaining putative small
      intestinal stem cells at cell position 4 and their absence in the colon.
AB  - Stem cells have been identified in two locations in small intestinal crypts;
      those intercalated between Paneth cells and another population (which retains DNA
      label) are located above the Paneth cell zone, at cell position 4. Because of
      disadvantages associated with the use of DNA label, doxycycline-induced transient
      transgenic expression of histone 2B (H2B)-green fluorescent protein (GFP) was
      investigated. H2B-GFP-retaining putative stem cells were consistently seen, with
      a peak at cell position 4, over chase periods of up to 112 days. After a 28-day
      chase, a subpopulation of the H2B-GFP-retaining cells was cycling, but the slow
      cycling status of the majority was illustrated by lack of expression of pHistone
      H3 and Ki67. Although some H2B-GFP-retaining cells were sensitive to low-dose
      radiation, the majority was resistant to low- and high-dose radiation-induced
      cell death, and a proportion of the surviving cells proliferated during
      subsequent epithelial regeneration. Long-term retention of H2B-GFP in a
      subpopulation of small intestinal Paneth cells was also seen, implying that they
      are long lived. In contrast to the small intestine, H2B-GFP-retaining epithelial
      cells were not seen in the colon from 28-day chase onward. This implies important
      differences in stem cell function between these two regions of the
      gastrointestinal tract, which may have implications for region-specific
      susceptibility to diseases (such as cancer and ulcerative colitis), in which
      epithelial stem cells and their progeny are involved.

PMID- 22997198
TI  - Preservation of hepatic blood flow by direct peritoneal resuscitation improves
      survival and prevents hepatic inflammation following hemorrhagic shock.
AB  - Conventional resuscitation (CR) from hemorrhagic shock (HS) results in gut and
      liver hypoperfusion, organ and cellular edema, and vital organ injury. Adjunct
      direct peritoneal resuscitation (DPR) with dialysate prevents gut
      vasoconstriction, hypoperfusion, and injury. We hypothesized that DPR might also
      improve hepatocellular edema, inflammation, and injury. Anesthetized male SD rats
      were assigned to groups (n = 8/group): 1) sham (no HS); 2) HS (40% MAP/60 min) +
      intravenous fluid conventional resuscitation [CR; shed blood + 2 vol saline
      (SAL)/30 min]; 3) HS+CR+DPR (30 ml ip 2.5% glucose dialysate); or 4) HS+CR+SAL
      (30 ml ip saline). Histopathology showed lung and liver injury in HS+CR and
      HS+CR+SAL up to 24-h postresuscitation (post-RES) that was not in shams and which
      was prevented by adjunct DPR. Wet-to-dry weight ratios in HS+CR revealed organ
      edema formation that was prevented by adjunct DPR. HS+CR and HS+CR+SAL had 34%
      mortality by 24-h post-RES, which was absent with DPR (0%). Liver IFN-gamma and
      IL-6 levels were elevated in CR compared with DPR or shams. TNF-alpha mRNA was
      upregulated in CR/sham and DPR/sham. IL-17 was downregulated in DPR/sham. CXCL10
      mRNA was upregulated in CR/sham but downregulated in DPR/sham. Despite restored
      central hemodynamic performance after CR of HS, liver blood flow was compromised
      up to 24 h post-RES, and the addition of DPR restores and maintains liver
      perfusion at 24-h post-RES. DPR prevented liver injury, histological damage, and
      edema formation compared with CR alone. DPR provided a mitigating anti
      inflammatory dampening of the systemic inflammatory response. In all, these
      effects likely account for improved survivorship in the DPR-treated group.

PMID- 22997200
TI  - Aortic pseudoaneurysm with fistulization to the left ventricle.

PMID- 22997202
TI  - Pediatric chronic lower respiratory disorders: microbiological and immunological
      phenotype.
AB  - The role of infectious agents in children with recurrent/chronic lower
      respiratory disorders (R/CLRDs) is not clear, whereas it has been largely studied
      in acute respiratory diseases. The purpose of the study was to evaluate the
      frequency of infections, in particular viral infections, in children with R/CLRDs
      correlating their presence with clinical/biohumoral parameters. Eighty children
      affected by R/CLRDs underwent bronchoscopy and analysis of bronchoalveolar lavage
      (BAL) for cells, mediators (eosinophil cationic protein-ECP, interleukin-IL-8,
      tumor necrosis factor-TNFalpha) and pathogens (viruses and bacteria). Viral
      genomes were detected in 50/80 (62.5%) children. Rhinovirus, the principal
      detected virus (26/50, 52%), occurred more frequently in male children. Higher
      percentages of BAL neutrophils and IL-8 values were detected in virus positive
      than negative children. ECP values resulted significantly higher in the children
      with rhinovirus than in those with other viruses. No other statistically
      significant correlation between viral findings and clinical/biohumoral data were
      found. Respiratory viruses, especially rhinovirus, seem to play an important role
      in children with R/CLRDs. They are associated with changes in BAL cellularity and
      inflammatory cytokines. Further studies are needed to confirm the persistence of
      viruses in these patients and to identify eventual therapeutic strategies.

PMID- 22997201
TI  - Absence of oncogenic canonical pathway mutations in aggressive pediatric rhabdoid
      tumors.
AB  - BACKGROUND: Rhabdoid tumors (also called atypical teratoid/rhabdoid tumor (AT/RT)
      in the brain), are highly malignant, poor prognosis lesions arising in the
      kidneys, soft tissues, and central nervous system. Targeted therapy in this
      disease would benefit from advanced technologies detecting relevant actionable
      mutations. PROCEDURE: Here we report on the evaluation of 25 tumors, all with
      known SMARCB1/INI1 alterations, for the presence of 983 different mutations in
      115 oncogenes and tumor-suppressor genes using OncoMap, a mass spectrometric
      method of allele detection. RESULTS: Other than mutations in SMARCB1, our results
      identified a single activating mutation in NRAS and complete absence of oncogenic
      mutations in all other genes tested. CONCLUSION: The absence of mutations in
      canonical pathways critical for development and progression of adult cancers
      suggests that distinct mechanisms drive these highly malignant pediatric tumors.
      This may limit the therapeutic utility of available targeted therapies and
      require a refocusing toward developmental and epigenetic pathways.

PMID- 22997203
TI  - Adenosine A(2B) receptor deficiency promotes host defenses against gram-negative
      bacterial pneumonia.
AB  - RATIONALE: Activation of the adenosine A(2B) receptor (A(2B)R) promotes
      antiinflammatory effects in diverse biological settings, but the role of this
      receptor in antimicrobial host defense in the lung has not been established. Gram
      negative bacillary pneumonia is a common and serious illness associated with high
      morbidity and mortality, the treatment of which is complicated by increasing
      rates of antibiotic resistance. OBJECTIVES: To test the hypothesis that absence
      of adenosine A(2B) receptor signaling promotes host defense against bacterial
      pneumonia. METHODS: We used a model of Klebsiella pneumoniae pneumonia in wild
      type mice and mice with targeted deletion of the A(2B)R. Host responses were
      compared in vivo and leukocyte responses to the bacteria were examined in vitro.
      MEASUREMENTS AND MAIN RESULTS: A(2B)R(-/-) mice demonstrated enhanced bacterial
      clearance from the lung and improved survival after infection with K. pneumoniae
      compared with wild-type controls, an effect that was mediated by bone marrow
      derived cells. Leukocyte recruitment to the lungs and expression of inflammatory
      cytokines did not differ between A(2B)R(-/-) and wild-type mice, but A(2B)R(-/-)
      neutrophils exhibited sixfold greater bactericidal activity and enhanced
      production of neutrophil extracellular traps compared with wild-type neutrophils
      when incubated with K. pneumoniae. Consistent with this finding, bronchoalveolar
      lavage fluid from A(2B)R(-/-) mice with Klebsiella pneumonia contained more
      extracellular DNA compared with wild-type mice with pneumonia. CONCLUSIONS: These
      data suggest that the absence of A(2B)R signaling enhances antimicrobial activity
      in gram-negative bacterial pneumonia.

PMID- 22997204
TI  - Natriuretic peptide-driven fluid management during ventilator weaning: a
      randomized controlled trial.
AB  - RATIONALE: Difficult weaning from mechanical ventilation is often associated with
      fluid overload. B-type natriuretic peptide (BNP) has been proposed as a tool for
      predicting and detecting weaning failure of cardiovascular origin. OBJECTIVES: To
      investigate whether fluid management guided by daily BNP plasma concentrations
      improves weaning outcomes compared with empirical therapy dictated by clinical
      acumen. METHODS: In a randomized controlled multicenter study, we allocated 304
      patients to either a BNP-driven or physician-driven strategy of fluid management
      during ventilator weaning. To standardize the weaning process, patients in both
      groups were ventilated with an automatic computer-driven weaning system. The
      primary end point was time to successful extubation. MEASUREMENTS AND MAIN
      RESULTS: In the BNP-driven group, furosemide and acetazolamide were given more
      often and in higher doses than in the control group, resulting in a more negative
      median (interquartile range) fluid balance during weaning (-2,320 [-4,735, 738]
      vs. -180 [-2,556, 2,832] ml; P < 0.0001). Time to successful extubation was
      significantly shorter with the BNP-driven strategy (58.6 [23.3, 139.8] vs. 42.4
      [20.8, 107.5] h; P = 0.034). The BNP-driven strategy increased the number of
      ventilator-free days but did not change length of stay or mortality. The effect
      on weaning time was strongest in patients with left ventricular systolic
      dysfunction. The two strategies did not differ significantly regarding
      electrolyte imbalance, renal failure, or shock. CONCLUSIONS: Our results suggest
      that a BNP-driven fluid management strategy decreases the duration of weaning
      without increasing adverse events, especially in patients with left ventricular
      systolic dysfunction. Clinical trial registered with www.clinicaltrials.gov
      (NCT00473148).

PMID- 22997205
TI  - Parent presence during invasive procedures and resuscitation: evaluating a
      clinical practice change.
AB  - RATIONALE: Parent presence during invasive procedures and/or resuscitation is a
      relatively underdeveloped and controversial practice. Much of the concern stems
      from the apprehension of the medical community. OBJECTIVES: To evaluate whether
      implementation of formal practice guidelines and corresponding interprofessional
      education would improve clinicians' sense of preparation and comfort in providing
      parents with options during their children's procedures. METHODS: Multiphase pre
      post survey of (1) clinician perceptions and (2) practice from the perspective of
      clinicians and parents experiencing the same procedure. Data were collected over
      4 years from a cardiovascular and critical care program in one U.S. children's
      hospital. MEASUREMENTS AND MAIN RESULTS: More than 70% of clinicians participated
      in the perception surveys (n = 782) and 538 clinicians and 274 parents
      participated in the practice surveys. After the intervention, clinicians reported
      that parents were present during more invasive procedures and reported higher
      levels of comfort with the practice of providing options to parents during
      resuscitative events. Levels of comfort were higher in clinicians who had
      practiced skills in a simulated learning environment. During both phases, few
      clinicians reported that parent presence affected their technical performance
      (4%), therapeutic decision-making (5%), or ability to teach (9%). During the post
      phase, clinicians reported more active parent behaviors during procedures.
      Parents who reported receiving information to help them prepare for their
      children's procedures reported higher levels of procedural understanding and
      emotional support. CONCLUSIONS: Implementation of practice guidelines and
      interprofessional education had a positive impact on clinicians' perceptions and
      practice when providing parents with options and support during their children's
      invasive procedures and/or resuscitation.

PMID- 22997206
TI  - Endogenous lung regeneration: potential and limitations.
AB  - The exploration of the endogenous regenerative potential of the diseased adult
      human lung represents an innovative and exciting task. In this pulmonary
      perspective, we discuss three major components essential for endogenous lung
      repair and regeneration: epithelial progenitor populations, developmental
      signaling pathways that regulate their reparative and regenerative potential, and
      the surrounding extracellular matrix in the human diseased lung. Over the past
      years, several distinct epithelial progenitor populations have been discovered
      within the lung, all of which most likely respond to different injuries by
      varying degrees. It has become evident that several progenitor populations are
      mutually involved in maintenance and repair, which is highly regulated by
      developmental pathways, such as Wnt or Notch signaling. Third, endogenous
      progenitor cells and developmental signaling pathways act in close spatiotemporal
      synergy with the extracellular matrix. These three components define and refine
      the highly dynamic microenvironment of the lung, which is altered in a disease
      specific fashion in several chronic lung diseases. The search for the right
      mixture to induce efficient and controlled repair and regeneration of the
      diseased lung is ongoing and will open completely novel avenues for the treatment
      of patients with chronic lung disease.

PMID- 22997207
TI  - Prediction of the clinical course of chronic obstructive pulmonary disease, using
      the new GOLD classification: a study of the general population.
AB  - RATIONALE: The new Global Initiative for Obstructive Lung Disease (GOLD)
      stratification of chronic obstructive pulmonary disease (COPD) into categories A,
      B, C, and D is based on symptoms, level of lung function, and history of
      exacerbations. OBJECTIVES: To investigate the abilities of this stratification to
      predict the clinical course of COPD. METHODS: Two similar population studies were
      performed in an area of Copenhagen including 6,628 individuals with COPD.
      MEASUREMENTS AND MAIN RESULTS: The patients were monitored for an average period
      of 4.3 years regarding COPD exacerbations, hospital admissions, and mortality.
      The percentages of individuals experiencing a COPD exacerbation during the first
      year of observation were 2.2% in group A, 5.8% in group B, 25.1% in group C, and
      28.6% in group D. One- and 3-year mortality rates were 0.6 and 3.8%,
      respectively, in group A, 3.0 and 10.6% in group B, 0.7 and 8.2% in group C, and
      3.4 and 20.1% in group D. Groups B and D, characterized by a higher degree of
      dyspnea than groups A and C, had five to eight times higher mortality from
      cardiovascular disease and cancer than did groups A and C. CONCLUSIONS: The new
      stratification performs well by identifying individuals at risk of exacerbations.
      Surprisingly, subgroup B, characterized by more severe dyspnea, had significantly
      poorer survival than group C, in spite of a higher FEV(1) level. This subgroup
      warrants special attention, as the poor prognosis could be caused by
      cardiovascular disease or cancer, requiring additional assessment and treatment.

PMID- 22997208
TI  - Proteome-base biomarkers in diabetes mellitus: progress on biofluids' protein
      profiling using mass spectrometry.
AB  - The worldwide number of individuals suffering from diabetes mellitus (DM) has
      been projected to rise from 171 million in 2000 to 366 million in 2030.
      Identification of specific biomarkers for prediction and monitoring of DM is
      needed not only for the adequate screening diagnosis but also to assist the
      design of interventions to prevent or delay progression of this pathology and its
      attendant complications. Proteomic methods based on MS hold special promise for
      the identification of novel biomarkers that might form the foundation for new
      clinical tests, but to date, their contribution has been somehow unfruitful.
      Indeed, from more than 300 proteins found differently modulated in body fluids
      from diabetic patients, approximately 50 were validated with other approaches
      like ELISA or Western blotting and the clinical trials are being initiated to
      employ biofluids' proteomics (specifically urinary proteomics) in clinical
      decision. This review provides an overview of MS-based applications in the
      identification of potential biomarkers for DM, emphasizing the methodological
      challenges involved.

PMID- 22997209
TI  - Utilization of a MAB for BRAF(V600E) detection in papillary thyroid carcinoma.
AB  - Identification of BRAF(V600E) in thyroid neoplasia may be useful because it is
      specific for malignancy, connotes a worse prognosis, and is the target of novel
      therapies currently under investigation. Sanger sequencing is the 'gold standard'
      for mutation detection but is subject to sampling error and requires resources
      beyond many diagnostic pathology laboratories. In this study, we compared
      immunohistochemistry (IHC) using a BRAF(V600E) mutation-specific MAB to Sanger
      sequencing on DNA from formalin-fixed paraffin-embedded tissue, in a well
      characterized cohort of 101 papillary thyroid carcinoma (PTC) patients. For all
      cases, an IHC result was available; however, five cases failed Sanger sequencing.
      Of the 96 cases with molecular data, 68 (71%) were BRAF(V600E) positive by IHC
      and 59 (61%) were BRAF(V600E) positive by sequencing. Eleven cases were
      discordant. One case was negative by IHC and initially positive by sequencing.
      Repeat sequencing of that sample and sequencing of a macrodissected sample were
      negative for BRAF(V600E). Of ten cases positive by IHC but negative by sequencing
      on whole sections, repeat sequencing on macrodissected tissue confirmed the IHC
      result in seven cases (suggesting that these were false negatives of sequencing
      on whole sections). In three cases, repeat sequencing on recut tissue remained
      negative (including using massive parallel sequencing), but these cases
      demonstrated relatively low neoplastic cellularity. We conclude that IHC for
      BRAF(V600E) is more sensitive and specific than Sanger sequencing in the routine
      diagnostic setting and may represent the new gold standard for detection of
      BRAF(V600E) mutation in PTC.

PMID- 22997210
TI  - Hospital-acquired listeriosis outbreak caused by contaminated diced celery-
      Texas, 2010.
AB  - BACKGROUND: Listeria monocytogenes causes often-fatal infections affecting mainly
      immunocompromised persons. Sources of hospital-acquired listeriosis outbreaks can
      be difficult to identify. We investigated a listeriosis outbreak spanning 7
      months and involving 5 hospitals. METHODS: Outbreak-related cases were identified
      by pulsed-field gel electrophoresis (PFGE) and confirmed by multiple-locus
      variable-number tandem-repeat analysis (MLVA). We conducted patient interviews,
      medical records reviews, and hospital food source evaluations. Food and
      environmental specimens were collected at a hospital (hospital A) where 6
      patients had been admitted before listeriosis onset; these specimens were tested
      by culture, polymerase chain reaction (PCR), and PFGE. We collected and tested
      food and environmental samples at the implicated processing facility. RESULTS:
      Ten outbreak-related patients were immunocompromised by >=1 underlying conditions
      or treatments; 5 died. All patients had been admitted to or visited an acute-care
      hospital during their possible incubation periods. The outbreak strain of L.
      monocytogenes was isolated from chicken salad and its diced celery ingredient at
      hospital A, and in 19 of >200 swabs of multiple surfaces and in 8 of 11 diced
      celery products at the processing plant. PCR testing detected Listeria in only 3
      of 10 environmental and food samples from which it was isolated by culturing. The
      facility was closed, products were recalled, and the outbreak ended. CONCLUSIONS:
      Contaminated diced celery caused a baffling, lengthy outbreak of hospital
      acquired listeriosis. PCR testing often failed to detect the pathogen, suggesting
      its reliability should be further evaluated. Listeriosis risk should be
      considered in fresh produce selections for immunocompromised patients.

PMID- 22997211
TI  - Schistosomiasis serology is valuable and reliable.

PMID- 22997213
TI  - Editorial commentary: turning the tide on HIV in women and children: preventing
      breast-milk HIV transmission while increasing maternal life expectancy.

PMID- 22997212
TI  - Pooled individual data analysis of 5 randomized trials of infant nevirapine
      prophylaxis to prevent breast-milk HIV-1 transmission.
AB  - BACKGROUND: In resource-limited settings, mothers infected with human
      immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their
      infants but risk transmitting HIV-1 or not breastfeed their infants and risk the
      infants dying of other infectious diseases or malnutrition. Recent results from
      observational studies and randomized clinical trials indicate daily
      administration of nevirapine to the infant can prevent breast-milk HIV-1
      transmission. METHODS: Data from 5396 mother-infant pairs who participated in 5
      randomized trials where the infant was HIV-1 negative at birth were pooled to
      estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV
      1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14
      weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks. RESULTS: The
      estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval
      [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for
      the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week
      nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week
      nevirapine regimen (log-rank test for trend, P < .001). Cox regression models
      with nevirapine as a time-varying covariate, stratified by trial site and
      adjusted for maternal CD4 cell count and infant birth weight, indicated that
      nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001)
      and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P <
      .001). CONCLUSIONS: Extended prophylaxis with nevirapine or with nevirapine and
      zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of
      prophylaxis results in a greater reduction in the risk of infection.

PMID- 22997214
TI  - Outbreak of carbapenem-resistant enterobacteriaceae containing blaNDM-1, Ontario,
      Canada.
AB  - BACKGROUND: New Delhi metallo-beta-lactamase (NDM) has emerged worldwide in
      clinically relevant gram-negative bacteria. We report an outbreak of NDM
      producing Klebsiella pneumoniae in patients with no prior travel history to
      endemic regions. METHODS: Five NDM-1-producing K. pneumoniae colonizing and/or
      clinically infecting patients in a community tertiary hospital were detected
      between October and November 2011. NDM-1-producing Enterobacteriaceae (K.
      pneumoniae and Escherichia coli) were clinically and epidemiologically
      characterized, including susceptibility profiles, molecular typing, and molecular
      characterization of plasmids and resistant determinants. RESULTS: Five patients
      were identified carrying NDM-1-producing K. pneumoniae, all of them
      epidemiologically linked with each other. K. pneumoniae were confirmed to belong
      to the same clone, exhibiting multidrug-resistant phenotypes. One patient was
      positive for NDM-1-producing E. coli in blood and E. coli and K. pneumoniae in
      rectal specimens, both containing the same bla(NDM) plasmid, suggesting
      horizontal transfer between species in the patient. No environmental sources of
      these strains were found. Detection of positive isolates directly from rectal
      specimens allowed the rapid identification and isolation of colonized patients.
      CONCLUSIONS: We report a NDM-1-producing K. pneumoniae outbreak in Ontario,
      Canada. Implementation of standard infection control practices, including active
      screening was able to contain the spread of this organism in the hospital
      setting. Of concern is the potential loss of a travel history to identify
      patients that are at high risk of being colonized or infected with this organism
      and the lack of an accurate, cost-effective test that can be implemented in the
      hospital setting to identify these multidrug-resistant organisms.

PMID- 22997215
TI  - Retinal examination can help identify disseminated tuberculosis in patients with
      HIV/AIDS.

PMID- 22997217
TI  - Water-based exercise in COPD with physical comorbidities: a randomised controlled
      trial.
AB  - Land-based exercise is often difficult for people with chronic obstructive
      pulmonary disease (COPD) who have coexisting obesity or musculoskeletal or
      neurological conditions. This randomised controlled trial aimed to determine the
      effectiveness of water-based exercise training in improving exercise capacity and
      quality of life compared to land-based exercise training and control (no
      exercise) in people with COPD and physical comorbidities. Participants referred
      to pulmonary rehabilitation were randomly allocated to a water-based exercise,
      land-based exercise or the control group. The two exercise groups trained for 8
      weeks, completing three sessions per week. 45 out of 53 participants (mean +/- SD
      age 72 +/- 9 years; forced expiratory volume in 1 s 59 +/- 15% predicted)
      completed the study. Compared to controls, water-based exercise training
      significantly increased 6-min walking distance, incremental and endurance shuttle
      walk distances, and improved Chronic Respiratory Disease Questionnaire (CRDQ)
      dyspnoea and fatigue. Compared to land-based exercise training, water-based
      exercise training significantly increased incremental shuttle walk distance (mean
      difference 39 m, 95% CI 5-72 m), endurance shuttle walk distance (mean difference
      228 m, 95% CI 19-438 m) and improved CRDQ fatigue. Water-based exercise training
      was significantly more effective than land-based exercise training and control in
      increasing peak and endurance exercise capacity and improving aspects of quality
      of life in people with COPD and physical comorbidities.

PMID- 22997218
TI  - Efficacy and safety of meropenem-clavulanate added to linezolid-containing
      regimens in the treatment of MDR-/XDR-TB.
AB  - Clinical experience on meropenem-clavulanate to treat tuberculosis (TB) is
      anecdotal (according to case reports on 10 patients). The aim of our case-control
      study was to evaluate the contribution of meropenem-clavulanate when added to
      linezolid-containing regimens in terms of efficacy and safety/tolerability in
      treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases
      after 3 months of second-line treatment. 37 cases with MDR-/XDR-TB were
      prescribed meropenem-clavulanate (3 g daily dose) in addition to a linezolid
      containing regimen (dosage range 300-1200 mg.day(-1)), designed according to
      international guidelines, which was prescribed to 61 controls. The clinical
      severity of cases was worse than that of controls (drug susceptibility profile,
      proportion of sputum-smear positive and of re-treatment cases). The group of
      cases yielded a higher proportion of sputum-smear converters (28 (87.5%) out of
      32 versus nine (56.3%) out of 16; p=0.02) and culture converters (31 (83.8%) out
      of 37 versus 15 (62.5%) out of 24; p=0.06). Excluding XDR-TB patients (11 (11.2%)
      out of 98), cases scored a significantly higher proportion of culture converters
      than controls (p=0.03). One case had to withdraw from meropenem-clavulanate due
      to increased transaminase levels. The results of our study provide: 1)
      preliminary evidence on effectiveness and safety/tolerability of meropenem
      clavulanate; 2) reference to design further trials; and 3) a guide to clinicians
      for its rationale use within salvage/compassionate regimens.

PMID- 22997219
TI  - Use of tuberculin skin test, IFN-gamma release assays and IFN-gamma-induced
      protein-10 to identify children with TB infection.
AB  - Current tests of tuberculosis (TB) infection (tuberculin skin test (TST),
      interferon (IFN)-gamma-release assays (IGRAs) and IFN-gamma-induced protein (IP)
      10) have limitations and their value when used consecutively to identify infected
      children has not been explored. This study describes TST, IGRA and IP-10
      responses in children in contact with adults with TB, the agreement of the tests
      and whether using multiple tests indentifies more infected children. 330 children
      (aged 1-15 yrs) in contact with adults with pulmonary TB and 156 controls were
      studied in Ethiopia. Children exposed to adults with high bacilli grades in
      sputum were more likely to have positive TST, IFN-gamma and IP-10 than controls.
      The agreement of positive tests was directly associated with the sputum bacilli
      grades (p<0.001 for all). The agreement of negative tests was higher in control
      children. The consecutive use of the tests increased the number of children
      classified as having at least one positive test. Using three tests increases the
      number of children classified as infected. This increase is associated with the
      bacilli load of the adults. Using only one test may underestimate the proportion
      of infected children, but the interpretation of the data is difficult due to the
      lack of reference standards.

PMID- 22997220
TI  - Confocal laser endomicroscopy for diagnosing lung cancer in vivo.
AB  - Confocal laser endomicroscopy is a novel endoscopic technique that may allow
      imaging of living cells in lung tissue in vivo. We assessed the potential of this
      technique for the detection of histology during screening bronchoscopy for lung
      cancer. 32 patients with suspected malignancies underwent bronchoscopy with
      endomicroscopy using acriflavine hydrochloride. Standardised areas and localised
      lesions were analysed by in vivo confocal imaging during bronchoscopy and
      biopsies were taken. Confocal images were graded and correlated prospectively
      with conventional histology from biopsies. Acriflavine hydrochloride yielded high
      quality confocal images and strongly labelled airway epithelial cells. No side
      effects were noted. 75,522 confocal images from 56 different locations were
      compared prospectively with histological data from biopsy specimens.
      Endomicroscopy allowed subsurface imaging with detailed analysis of cellular and
      subcellular structures. Neoplastic changes could be predicted with high accuracy
      (sensitivity 96.0%, specificity 87.1%, accuracy 91.0%). Confocal laser
      endomicroscopy with acriflavine is a novel diagnostic tool for the analysis of
      living cells during bronchoscopy and permits virtual histology of neoplastic
      changes in the airways with high accuracy. This technique may enable the rapid
      diagnosis of neoplasia during ongoing endoscopy in patients with suspected lung
      cancer.

PMID- 22997221
TI  - Implantable cardioverter defibrillator lead implantation in patients with a
      persistent left superior vena cava--feasibility, chances, and limitations:
      representative cases in adults.
AB  - AIMS: Device implantation may be challenging in patients with venous
      abnormalities. The most common congenital variation--frequently associated with
      other congenital abnormalities--is described as persistent left superior vena
      cava (PLSVC). METHODS AND RESULTS: The present case series demonstrates
      successful implantable cardioverter defibrillator (ICD) lead implantation in the
      most common anatomic variations of PLSVC. All types of current ICD models (single
      and dual chamber, VDD, and cardiac resynchronization therapy devices) were used.
      Angiographic findings and implantation techniques (e.g. guiding and diagnostic
      catheters, wires, occlusion balloons, and rotation sequences) are presented in
      images and movie sequences. CONCLUSION: Device implantation in patients with
      PLSVC may be complex but a successful transvenous approach is possible in most of
      the cases. Careful imaging prior to implantation procedure is essential for
      understanding the individual anatomy and in order to choose adequate material and
      implantation strategy.

PMID- 22997222
TI  - Permanent His-bundle pacing maintains long-term ventricular synchrony and left
      ventricular performance, unlike conventional right ventricular apical pacing.
AB  - AIMS: Right ventricular apical pacing (RVAP) may be deleterious, determining
      abnormal left ventricular (LV) electrical activation and progressive LV
      dysfunction. Permanent His-bundle pacing (HBP) has been proposed to prevent this
      detrimental effect. The aim of our study was to compare the long-term effects of
      HBP on LV synchrony and systolic performance with those of RVAP in the same group
      of patients. METHODS: Our analysis included 26 patients who received both an HBP
      lead and an RVAP lead, as backup, in our electrophysiology laboratory between
      2004 and 2007. After implantation, all devices were programmed to obtain HBP. An
      intra-patient comparison of the effects of HBP and RVAP on LV dyssynchrony and
      function was performed at the last available follow-up examination. RESULTS:
      After a mean of 34.6 +/- 11 months, the pacing modality was temporarily switched
      to RVAP. During RVAP, LV ejection fraction significantly decreased (50.1 +/- 8.8%
      vs. 57.3 +/- 8.5%, P < 0.001), mitral regurgitation significantly increased (22.5
      +/- 10.9% vs.16.3 +/- 12.4%; P = 0.018), and inter-ventricular delay
      significantly worsened (33.4 +/- 19.5 ms vs. 7.1 +/- 4.7 ms, P = 0.003) in
      comparison with HBP. However, the myocardial performance index was not
      statistically different between the two pacing modalities (P = 0.779). No
      asynchrony was revealed by tissue Doppler imaging during HBP, while during RVAP
      the asynchrony index was significantly higher in both the four-chamber (125.8 +/-
      63.9 ms; P = 0.035 vs. HBP) and two-chamber (126 +/- 86.5 ms; P = 0.037 vs. HBP)
      apical views. CONCLUSION: His-bundle pacing has long-term positive effects on
      inter- and intra-ventricular synchrony and ventricular contractile performance in
      comparison with RVAP. It prevents asynchronous pacing-induced LV ejection
      fraction depression and mitral regurgitation.

PMID- 22997223
TI  - Assessment of a pay-for-performance program in primary care designed by target
      users.
AB  - BACKGROUND: Evidence for pay-for-performance (P4P) has been searched for in the
      last decade as financial incentives increased to influence behaviour of health
      care professionals to improve quality of care. The effectiveness of P4P is
      inconclusive, though some reviews reported significant effects. OBJECTIVE: To
      assess changes in performance after introducing a participatory P4P program.
      DESIGN: An observational study with a pre- and post-measurement. Setting and
      subjects. Sixty-five general practices in the south of the Netherlands.
      Intervention. A P4P program designed by target users containing indicators for
      chronic care, prevention, practice management and patient experience (general
      practitioner's [GP] functioning and organization of care). Quality indicators
      were calculated for each practice. A bonus with a maximum of 6890 Euros per 1000
      patients was determined by comparing practice performance with a benchmark. MAIN
      OUTCOME MEASURES: Quality indicators for clinical care (process and outcome) and
      patient experience. RESULTS: We included 60 practices. After 1 year, significant
      improvement was shown for the process indicators for all chronic conditions
      ranging from +7.9% improvement for cardiovascular risk management to +11.5% for
      asthma. Five outcome indicators significantly improved as well as patients'
      experiences with GP's functioning and organization of care. No significant
      improvements were seen for influenza vaccination rate and the cervical cancer
      screening uptake. The clinical process and outcome indicators, as well as patient
      experience indicators were affected by baseline measures. Smaller practices
      showed more improvement. CONCLUSIONS: A participatory P4P program might stimulate
      quality improvement in clinical care and improve patient experiences with GP's
      functioning and the organization of care.

PMID- 22997224
TI  - Effectiveness of oseltamivir in adults: a meta-analysis of published and
      unpublished clinical trials.
AB  - BACKGROUND: Oseltamivir is widely used for the treatment of influenza. Previous
      systematic reviews suggest that they reduce complications, but had significant
      methodologic limitations. OBJECTIVE: To assess the effect of oseltamivir on
      duration of symptoms, complications and hospitalizations in adults. METHODS: We
      searched Medline without time or language restrictions, and trial registries
      maintained by the manufacturer. We included published and unpublished randomized
      double-blinded, placebo-controlled trials of oseltamivir in adults with suspected
      influenza that reported duration of symptoms, complications or hospitalizations.
      We abstracted data regarding study quality, the duration of symptoms and rates of
      complications and hospitalization. RESULTS: Three published and eight unpublished
      studies met our inclusion criteria. For the intention-to-treat (ITT) population,
      the mean reduction in the duration of symptoms was 20.7 hours [95% confidence
      interval (CI) 13.3 to 28.0 hours]. Two large unpublished studies in the elderly
      and in adults with chronic disease did not find a significant reduction in the
      symptom duration. There was no difference in the likelihood of hospitalization in
      the ITT population (33/2633 patients for oseltamivir versus 20/1694 for placebo).
      The rate of complications in the intention-to-treat infected (ITTI) population
      was reduced when acute bronchitis was included (-2.8%, 95% CI -0.6 to -4.9), but
      not when it was excluded. The risk of pneumonia was reduced in the ITTI
      population (-0.9%, 95% CI -0.1 to -1.7) but not in the ITT population.
      CONCLUSIONS: There is no evidence that oseltamivir reduces the likelihood of
      hospitalization, pneumonia or the combined outcome of pneumonia, otitis media and
      sinusitis in the ITT population.

PMID- 22997225
TI  - Drp1-mediated mitochondrial dynamics and survival of developing chick motoneurons
      during the period of normal programmed cell death.
AB  - Mitochondrial morphology is dynamically remodeled by fusion and fission in
      neurons, and this process is implicated in nervous system development and
      pathology. However, the mechanism by which mitochondrial dynamics influence
      neuronal development is less clear. In this study, we found that the length of
      mitochondria is progressively reduced during normal development of chick embryo
      motoneurons (MNs), a process partly controlled by a fission-promoting protein,
      dynamin-related protein 1 (Drp1). Suppression of Drp1 activity by gene
      electroporation of dominant-negative mutant Drp1 in a subset of developing MNs
      increased mitochondrial length in vivo, and a greater proportion of Drp1
      suppressed MNs underwent programmed cell death (PCD). By contrast, the survival
      of nontransfected MNs in proximity to the transfected MNs was significantly
      increased, suggesting that the suppression of Drp1 confers disadvantage during
      the competition for limited survival signals. Because we also monitored
      perturbation of neurite outgrowth and mitochondrial membrane depolarization
      following Drp1 suppression, we suggest that impairments of ATP production and
      axonal growth may be downstream factors that influence the competition of MNs for
      survival. Collectively, these results indicate that mitochondrial dynamics are
      required for normal axonal development and competition-dependent MN PCD.

PMID- 22997226
TI  - Regulation of Anopheles gambiae male accessory gland genes influences postmating
      response in female.
AB  - In Drosophila, the accessory gland proteins (Acps) secreted from the male
      accessory glands (MAGs) and transferred along with sperm into the female
      reproductive tract have been implicated in triggering postmating behavioral
      changes, including refractoriness to subsequent mating and propensity to egg
      laying. Recently, Acps have been found also in Anopheles, suggesting similar
      functions. Understanding the mechanisms underlying transcriptional regulation of
      Acps and their functional role in modulating Anopheles postmating behavior may
      lead to the identification of novel vector control strategies to reduce mosquito
      populations. We identified heat-shock factor (HSF) binding sites within the Acp
      promoters of male Anopheles gambiae and discovered three distinct Hsf isoforms;
      one being significantly up-regulated in the MAGs after mating. Through genome
      wide transcription analysis of Hsf-silenced males, we observed significant down
      regulation in 50% of the Acp genes if compared to control males treated with a
      construct directed against an unrelated bacterial sequence. Treated males
      retained normal life span and reproductive behavior compared to control males.
      However, mated wild-type females showed a ~46% reduction of egg deposition rate
      and a ~23% reduction of hatching rate (~58% combined reduction of progeny). Our
      results highlight an unsuspected role of HSF in regulating Acp transcription in
      A. gambiae and provide evidence that Acp down-regulation in males leads a
      significant reduction of progeny, thus opening new avenues toward the development
      of novel vector control strategies.

PMID- 22997227
TI  - Perinatal manipulation of alpha-linolenic acid intake induces epigenetic changes
      in maternal and offspring livers.
AB  - Previous studies indicated that the intake of alpha-linolenic acid (ALA) can
      alter the concentration of both omega-6 and omega-3 fatty acids in both mother
      and offspring, with consequences on postnatal brain development. This study
      describes the association between maternal ALA availability during gestation and
      lactation, and alterations in the Fads2 DNA methylation in both maternal and
      offspring livers, at the end of lactation period. Both Fads2 promoter and intron
      1 DNA methylation were increased in the groups receiving postnatal flaxseed oil
      containing 50% ALA (mothers or pups), while bivariate analysis indicated a
      significant association of the Fads2 epigenetic status in the liver between each
      mother and its offspring. In addition, Fads2 expression was negatively correlated
      with promoter methylation at the individual level in maternal livers (P<0.05).
      This study also indicated that the interplay between ALA availability during
      gestation and lactation can differentially alter the expression of desaturases
      and elongases involved in omega-6 and omega-3 metabolic pathways. In summary,
      when considering the perinatal dietary ALA requirements in mice, both gestation
      and lactation periods should be considered as having distinct roles in modulating
      the metabolism of omega-6 and omega-3 fatty acids in maternal mouse livers.

PMID- 22997229
TI  - Moving the field of B lymphopoiesis.

PMID- 22997228
TI  - Dual suppression of hemangiogenesis and lymphangiogenesis by splice-shifting
      morpholinos targeting vascular endothelial growth factor receptor 2 (KDR).
AB  - The KDR gene, which participates in angiogenesis and lymphangiogenesis, produces
      two functionally distinct protein products, membrane-bound KDR (mbKDR) and its
      isoform, soluble KDR (sKDR). Since sKDR does not have a tyrosine kinase domain
      and does not dimerize, it is principally an antagonist of lymphangiogenesis by
      sequestering VEGF-C. Alternative polyadenylation of exon 30 or intron 13 leads to
      the production of mbKDR or sKDR, respectively, yet the regulatory mechanisms are
      unknown. Here we show that an antisense morpholino oligomer directed against the
      exon 13-intron 13 junction increases sKDR (suppressing lymphangiogenesis) and
      decreases mbKDR (inhibiting hemangiogenesis). The latent polyadenylation site in
      intron 13 of KDR is activated by blocking the upstream 5' splicing site with an
      antisense morpholino oligomer. Intravitreal morpholino injection suppressed laser
      choroidal neovascularization while increasing sKDR. In the mouse cornea,
      subconjunctival injection of the morpholino-inhibited corneal angiogenesis and
      lymphangiogenesis, and suppressed graft rejection after transplantation. Thus,
      this morpholino can be used for concurrent suppression of hemangiogenesis and
      lymphangiogenesis. This study offers new insight into the mechanisms and
      potential therapeutic modulation of alternative polyadenylation.

PMID- 22997230
TI  - Resolution and characterization of pro-B and pre-pro-B cell stages in normal
      mouse bone marrow. 1991.

PMID- 22997232
TI  - Retraction: Transcription factor Gfi1 restricts B cell-mediated autoimmunity.

PMID- 22997231
TI  - Microbial-induced Th17: superhero or supervillain?
AB  - Th17 cells are an effector lineage of CD4 T cells that can contribute to
      protection against microbial pathogens and to the development of harmful
      autoimmune and inflammatory conditions. An increasing number of studies suggests
      that Th17 cells play an important protective role in mobilizing host immunity to
      extracellular and intracellular microbial pathogens, such as Candida and
      Salmonella. Furthermore, the generation of Th17 cells is heavily influenced by
      the normal microbial flora, highlighting the complex interplay among harmless
      microbes, pathogens, and host immunity in the regulation of pathogen-specific
      Th17 responses. In this article, we review the current understanding of microbe
      induced Th17 cells in the context of infectious and inflammatory disease.

PMID- 22997234
TI  - HIV-1 transmission goes retro (steps back).

PMID- 22997233
TI  - Previously transmitted HIV-1 strains are preferentially selected during
      subsequent sexual transmissions.
AB  - BACKGROUND: A genetic bottleneck is known to exist for human immunodeficiency
      virus (HIV) at the point of sexual transmission. However, the nature of this
      bottleneck and its effect on viral diversity over time is unclear. METHODS:
      Interhost and intrahost HIV diversity was analyzed in a stable population in
      Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals
      in initially HIV-discordant relationships in which transmission occurred later
      were examined using Sanger sequencing of bulk polymerase chain reaction (PCR)
      products (for 22 couples), clonal analysis (for 3), and next-generation deep
      sequencing (for 9). RESULTS: Intrahost viral diversity was significantly higher
      than changes in interhost diversity (P < .01). The majority of HIV-1-discordant
      couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and
      next-generation deep sequencing (6 of 9) demonstrated that the viral populations
      present in the newly infected recipient were more closely related to the donor
      partner's HIV-1 variants found earlier during infection as compared to those
      circulating near the estimated time of transmission (P = .03). CONCLUSIONS: These
      findings suggest that sexual transmission constrains viral diversity at the
      population level, partially because of the preferential transmission of ancestral
      as opposed to contemporary strains circulating in the transmitting partner.
      Future successful vaccine strategies may need to target these transmitted
      ancestral strains.

PMID- 22997238
TI  - Morphological and cytochemical aspects of spermatozoa in the genus Cochliomyia
      (Diptera: Calliphoridae).
AB  - The objective of this study was to characterize, structurally and
      ultrastructurally, the spermatozoa of the screwworm flies Cochliomyia hominivorax
      and Cochliomyia macellaria. To visualize the ultrastructure of microtubules and
      identify basic proteins, techniques such as the tannic acid fixation and the
      cytochemical method of ethanolic phosphotungstic acid (EPTA) were used. These
      methods of fixation are important because they reinforce the evidence of the
      protofilaments present in the microtubular wall and identify basic proteins,
      respectively. With the tannic acid fixative it was possible to observe a
      significant number of microtubules in the cell cytoplasm during spermiogenesis.
      Microtubules were observed in all regions of spermatids (head, 'overlap' zone and
      tail). The EPTA technique highlighted the presence of basic proteins on the
      border of the nucleus and nuclear envelope in the two species analyzed, and in
      the centriolar adjunct and on the border of mitochondrial derivatives in C.
      macellaria. The axoneme is of a conventional insect type with a 9 + 9 + 2
      microtubular arrangement and the spermatozoa of C. hominivorax and C. macellaria
      are similar to those described for other Brachycera. The spermatozoa are long and
      thin in these two species, ~190 um in length, of which the head region measures
      ~26 um in C. hominivorax and 29 um in C. macellaria. A polymorphism was observed
      in C. hominivorax and C. macellaria. These features are consistent with the
      structural diversity of the dipteran spermatozoa, constituting an essential tool
      for understanding the complex variations found in the Diptera order.

PMID- 22997235
TI  - Long-term and short-term evolutionary impacts of transposable elements on
      Drosophila.
AB  - Transposable elements (TEs) are considered to be genomic parasites and their
      interactions with their hosts have been likened to the coevolution between host
      and other nongenomic, horizontally transferred pathogens. TE families, however,
      are vertically inherited as integral segments of the nuclear genome. This
      transmission strategy has been suggested to weaken the selective benefits of host
      alleles repressing the transposition of specific TE variants. On the other hand,
      the elevated rates of TE transposition and high incidences of deleterious
      mutations observed during the rare cases of horizontal transfers of TE families
      between species could create at least a transient process analogous to the
      influence of horizontally transmitted pathogens. Here, we formally address this
      analogy, using empirical and theoretical analysis to specify the mechanism of how
      host-TE interactions may drive the evolution of host genes. We found that host TE
      interacting genes actually have more pervasive evidence of adaptive evolution
      than immunity genes that interact with nongenomic pathogens in Drosophila. Yet,
      both our theoretical modeling and empirical observations comparing Drosophila
      melanogaster populations before and after the horizontal transfer of P elements,
      which invaded D. melanogaster early last century, demonstrated that horizontally
      transferred TEs have only a limited influence on host TE-interacting genes. We
      propose that the more prevalent and constant interaction with multiple vertically
      transmitted TE families may instead be the main force driving the fast evolution
      of TE-interacting genes, which is fundamentally different from the gene-for-gene
      interaction of host-pathogen coevolution.

PMID- 22997237
TI  - Trade-off between selection for dosage compensation and masculinization on the
      avian Z chromosome.
AB  - Following the suppression of recombination, gene expression levels decline on the
      sex-limited chromosome, and this can lead to selection for dosage compensation in
      the heterogametic sex to rebalance average expression from the X or Z chromosome
      with average autosomal expression. At the same time, due to their unequal pattern
      of inheritance in males and females, the sex chromosomes are subject to
      unbalanced sex-specific selection, which contributes to a nonrandom distribution
      of sex-biased genes compared to the remainder of the genome. These two forces act
      against each other, and the relative importance of each is currently unclear. The
      Gallus gallus Z chromosome provides a useful opportunity to study the importance
      and trade-offs between sex-specific selection and dosage compensation in shaping
      the evolution of the genome as it shows incomplete dosage compensation and is
      also present twice as often in males than females, and therefore predicted to be
      enriched for male-biased genes. Here, we refine our understanding of the
      evolution of the avian Z chromosome, and show that multiple strata formed across
      the chromosome over ~130 million years. We then use this evolutionary history to
      examine the relative strength of selection for sex chromosome dosage compensation
      vs. the cumulative effects of masculinizing selection on gene expression. We find
      that male-biased expression increases over time, indicating that selection for
      dosage compensation is relatively less important than masculinizing selection in
      shaping Z chromosome gene expression.

PMID- 22997236
TI  - Unusual and typical features of a novel restorer-of-fertility gene of sugar beet
      (Beta vulgaris L.).
AB  - Male gametogenesis in plants can be impaired by an incompatibility between
      nuclear and mitochondrial genomes, termed cytoplasmic male sterility (CMS). A
      sterilizing factor resides in mitochondria, whereas a nuclear factor, Restorer-of
      fertility (Rf), restores male fertility. Although a majority of plant Rf genes
      are thought to encode a family of RNA-binding proteins called pentatrico-peptide
      repeat (PPR) proteins, we isolated a novel type of Rf from sugar beet. Two BACs
      and one cosmid clone that constituted a 383-kbp contig covering the sugar beet
      Rf1 locus were sequenced. Of 41 genes borne by the contig, quadruplicated genes
      were found to be associated with specific transcripts in Rf1 flower buds. The
      quadruplicated genes encoded a protein resembling OMA1, a protein known from
      yeast and mammals to be involved in mitochondrial protein quality control.
      Construction of transgenic plants revealed that one of the four genes (bvORF20)
      was capable of restoring partial pollen fertility to CMS sugar beet; the level of
      restoration was comparable to that evaluated by a crossing experiment. However,
      the other genes lacked such a capability. A GFP-fusion experiment showed that
      bvORF20 encoded a mitochondrial protein. The corresponding gene was cloned from
      rf1rf1 sugar beet and sequenced, and a solitary gene that was similar but not
      identical to bvORF20 was found. Genetic features exhibited by sugar beet Rf1,
      such as gene clustering and copy-number variation between Rf1 and rf, were
      reminiscent of PPR-type Rf, suggesting that a common evolutionary mechanism(s)
      operates on plant Rfs irrespective of the translation product.

PMID- 22997240
TI  - Identification of alg3 in the mushroom-forming fungus Schizophyllum commune and
      analysis of the Deltaalg3 knockout mutant.
AB  - Alg3 of Saccharomyces cerevisiae catalyzes the mannosyl transfer from Man-P-Dol
      to Man(5)GlcNAc(2)-PP-Dol resulting in the formation of Man(6)GlcNAc(2)-PP-Dol,
      which is then further processed to the final precursor oligosaccharide
      Glc(3)Man(9)GlcNAc(2) for N-glycosylation of proteins. Here, we identified the
      alg3 gene of the mushroom-forming fungus Schizophyllum commune by homology
      search. Its function was confirmed by the complementation of the Deltaalg3 strain
      of S. cerevisiae. Inactivation of alg3 in S. commune resulted in the production
      of predominantly Man(3)GlcNAc(2) protein-linked N-glycans. No impact on growth
      nor a developmental phenotype due to the deletion was observed. This provides a
      first step toward engineering of a homogeneous, humanized N-glycosylation pattern
      for the production of therapeutic glycoproteins in mushrooms.

PMID- 22997239
TI  - Dual suppression of the cyclin-dependent kinase inhibitors CDKN2C and CDKN1A in
      human melanoma.
AB  - Resistance to BRAF(V600E) inhibitors is associated with reactivation of mitogen
      activated protein kinase (MAPK) signaling at different levels in melanoma. To
      identify downstream effectors of MAPK signaling that could be used as potential
      additional therapeutic targets for BRAF(V600E) inhibitors, we used
      hTERT/CDK4R24C/p53DD-immortalized primary human melanocytes genetically modified
      to ectopically express BRAF   (   V600E   ) or NRAS   (   G12D   ) and observed
      induction of the AP-1 transcription factor family member c-Jun. Using a dominant
      negative approach, in vitro cell proliferation assays, western blots, and flow
      cytometry showed that MAPK signaling via BRAF(V600E) promotes melanoma cell
      proliferation at G1 through AP-1-mediated negative regulation of the INK4 family
      member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family
      member, cyclin-dependent kinase inhibitor 1A (CDKN1A). These effects were
      antagonized by pharmacological inhibition of CDKN2C and CDKN1A targets CDK2 and
      CDK4 in vitro. In contrast to BRAF   (   V600E   ) or NRAS   (   G12D   )
      expressing melanocytes, melanoma cells have an inherent resistance to suppression
      of AP-1 activity by BRAF(V600E)- or MEK-inhibitors. Here, CDK2/4 inhibition
      statistically significantly augmented the effects of BRAF(V600E)- or MEK
      inhibitors on melanoma cell viability in vitro and growth in athymic nude Foxn1  
      (   nu   ) mice (P = .03 when mean tumor volume at day 13 was compared for
      BRAF(V600E) inhibitor vs BRAF(V600E) inhibitor plus CDK2/4 inhibition; P = .02
      when mean tumor volume was compared for MEK inhibitor vs MEK inhibitor plus
      CDK2/4 inhibition; P values were calculated by a two-sided Welch t test; n = 4-8
      mice per group).

PMID- 22997241
TI  - Toxoplasma gondii secretory proteins bind to sulfated heparin structures.
AB  - Toxoplasma gondii is the causative agent of toxoplasmosis, one of the most
      widespread infections in humans and animals, and is a major opportunistic
      pathogen in immunocompromised patients. Toxoplasma gondii is unique as it can
      invade virtually any nucleated cell, although the mechanisms are not completely
      understood. Parasite attachment to the host cell is a prerequisite for
      reorientation and penetration and likely requires the recognition of molecules at
      the host cell surface. It has been reported that the affinity of tachyzoites, the
      invasive form of T. gondii, for host cells can be inhibited by a variety of
      soluble-sulfated glycosaminoglycans (GAGs), such as heparan sulfate. Using
      heparin-functionalized zeolites in the absence of host cells, we visualized
      heparin-binding sites on the surface of tachyzoites by confocal and atomic force
      microscopy. Furthermore, we report that protein components of the parasite
      rhoptry, dense granule and surface bind GAGs. In particular, the proteins ROP2
      and ROP4 from the rhoptry, GRA2 from the dense granules and the surface protein
      SAG1 were found to bind heparin. The binding specificities and affinities of
      individual parasite proteins for natural heparin and heparin oligosaccharides
      were determined by a combination of heparin oligosaccharide microarrays and
      surface plasmon resonance. Our results suggest that interactions between sulfated
      GAGs and parasite surface antigens contribute to T. gondii attachment to host
      cell surfaces as well as initiating the invasion process, while rhoptries and
      dense granule organelles may play an important role during the establishment of
      the infection and during the life of the parasite inside the parasitophorous
      vacuole.

PMID- 22997242
TI  - Human gastric TFF2 peptide contains an N-linked fucosylated N,N'
      diacetyllactosediamine (LacdiNAc) oligosaccharide.
AB  - In the human stomach, the peptide trefoil factor family 2 (TFF2) is secreted
      together with the mucin MUC6 by mucous neck cells (MNCs) and antral gland cells.
      TFF2 is strongly associated with the gastric mucus and promotes gastric
      restitution. Here, TFF2 was purified from the human corpus and antrum,
      respectively, by size-exclusion chromatography, and the N-linked glycan structure
      at N-15 of the mature peptide was determined. As a hallmark, the unusual
      monofucosylated N,N'-diacetylhexosediamine (tentatively assigned as GalNAcbeta1 
      > 4GlcNAc, LacdiNAc) modification was detected as the terminal structure of a bi
      antennary complex type N-glycan exhibiting also core fucosylation. Replicate
      analyses did not show microheterogeneities in the fraction of peptide-N
      glycosidase F cleaved and permethylated N-glycans when analyzed by matrix
      assisted laser desorption ionization (MALDI) mass spectrometry (MS). On the
      glycopeptide level, a minor glycan microheterogeneity was evident in liquid
      chromatography-electrospray ionization (ESI)-MS, demonstrating the presence of
      underfucosylated species. The tryptic TFF2 N-glycopeptide p34-39 (LSPHNR N
      glycosylated with Fuc3Hex3HexNAc6) was identified by both ESI-tandem mass
      spectrometry and MALDI-post-source decay analysis. Lectin analyses with the
      Wisteria floribunda agglutinin indicated the potential presence of LacdiNAc
      terminating glycans and revealed minor differences between TFF2 from fundic
      units, i.e. MNCs, and antral units, i.e. antral gland cells. Strikingly, on the
      level of the primary structure, there was no indication that the formation of the
      proposed LacdiNAc structure is cis-controlled by a peptidic determinant related
      to the published sequences.

PMID- 22997244
TI  - Photo quiz. Asymptomatic plaques on toe web.

PMID- 22997247
TI  - Ultrasound diagnosed adenomyosis has a negative impact on successful implantation
      following GnRH antagonist IVF treatment.
AB  - STUDY QUESTION: Does the presence of ultrasound diagnosed adenomyosis interfere
      with successful implantation in patients undergoing IVF treatment with GnRH
      antagonist ovarian stimulation? SUMMARY ANSWER: The presence of ultrasound
      diagnosed adenomyosis was associated with a significant reduction in successful
      implantation of good quality embryos in patients undergoing GnRH antagonist
      stimulation for IVF treatment (viable clinical pregnancy rate 23.6% versus 44.6%,
      P= 0.017). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: There is currently no
      consensus regarding the impact of adenomyosis on implantation potential. Although
      some studies have identified alterations in the endometrial milieu in adenomyosis
      patients that may impact implantation, several papers have reported no associated
      reproductive deficit. However, these pregnancy outcome studies have primarily
      investigated patients undergoing long down-regulation IVF protocols, where low
      levels of serum estrogen (before commencing the ovarian stimulation) may
      inactivate the adenomyosis and potentially negate its effect on implantation.
      Given that the majority of fertility clinics are now moving towards the more
      'patient-friendly' antagonist protocol, where patients are not placed in a hypo
      estrogen state before commencing ovarian stimulation, the question of whether
      adenomyosis has an impact on IVF success rates in GnRH antagonist-stimulated IVF
      treatment needs to be examined. DESIGN: This is a retrospective cohort study of
      748 patients who, between April 2010 and March 2012, underwent a screening
      transvaginal ultrasound to identify possible pelvic pathology before commencing
      their IVF treatment. From this screening group, 213 patients were eligible to be
      included in the study as they had no obvious underlying uterine or embryonic
      factors that could have interfered with successful implantation (aged <=39 years,
      good quality Day 4/5 embryo for single-embryo transfer, no uterine
      fibroids/hydrosalpinx or endometrial polyps). PARTICIPANTS AND SETTING: There
      were 213 patients in a private IVF unit eligible to be included in the study,
      with 38 patients (17.84%) having ultrasound diagnosed adenomyosis and 175
      patients having no adenomyosis on the scan. Only the first treatment cycle for
      each patient was included. MAIN RESULTS AND THE ROLE OF CHANCE: The adenomyosis
      group had a viable clinical pregnancy rate of 23.6% compared with 44.6% in the
      non-adenomyosis group (P =0.017). However, the median maternal age and duration
      of infertility of the adenomyosis group was 2 years older and 4 months greater,
      respectively, than that of the non-adenomyosis group. A logistic regression
      analysis was performed to account for these differences between the two groups,
      with the adjusted results still showing a statistically significant decline in
      viable pregnancy rate in the adenomyosis group (OR = 0.408, CI = 0.181-0.922, P
      =0.031 when adjusting for maternal age; OR = 0.417, CI = 0.175-0.989, P =0.047
      when adjusting for duration of infertility) BIAS, CONFOUNDING AND OTHER REASONS
      FOR CAUTION: Given the retrospective nature of this study, there is risk of bias.
      This risk was minimized by having subjective variables such as embryo quality
      assessed by individuals not involved in the study, while strictly applying the
      pre-determined inclusion/exclusion criteria to all study participants.
      Furthermore, it is acknowledged that ultrasound is   not a perfect test for the
      diagnosis of adenomyosis and, therefore, may underestimate the incidence of
      adenomyosis by misclassifying some patients with mild adenomyosis as not
      affected. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study should be
      representative of outcomes for any patient undergoing a GnRH antagonist ovarian
      stimulation cycle for IVF since standard IVF treatment protocols were used. STUDY
      FUNDING/COMPETING INTEREST: MSD Australia have provided us with a small amount of
      funding to cover our costs (including a travel grant for Dr Thalluri to present
      this work at a conference).

PMID- 22997248
TI  - Anchored p90 ribosomal S6 kinase 3 is required for cardiac myocyte hypertrophy.
AB  - RATIONALE: Cardiac myocyte hypertrophy is the main compensatory response to
      chronic stress on the heart. p90 ribosomal S6 kinase (RSK) family members are
      effectors for extracellular signal-regulated kinases that induce myocyte growth.
      Although increased RSK activity has been observed in stressed myocytes, the
      functions of individual RSK family members have remained poorly defined, despite
      being potential therapeutic targets for cardiac disease. OBJECTIVE: To
      demonstrate that type 3 RSK (RSK3) is required for cardiac myocyte hypertrophy.
      METHODS AND RESULTS: RSK3 contains a unique N-terminal domain that is not
      conserved in other RSK family members. We show that this domain mediates the
      regulated binding of RSK3 to the muscle A-kinase anchoring protein scaffold,
      defining a novel kinase anchoring event. Disruption of both RSK3 expression using
      RNA interference and RSK3 anchoring using a competing muscle A-kinase anchoring
      protein peptide inhibited the hypertrophy of cultured myocytes. In vivo, RSK3
      gene deletion in the mouse attenuated the concentric myocyte hypertrophy induced
      by pressure overload and catecholamine infusion. CONCLUSIONS: Taken together,
      these data demonstrate that anchored RSK3 transduces signals that modulate
      pathologic myocyte growth. Targeting of signaling complexes that contain select
      kinase isoforms should provide an approach for the specific inhibition of cardiac
      myocyte hypertrophy and for the development of novel strategies for the
      prevention and treatment of heart failure.

PMID- 22997249
TI  - Clinical outcome of arterial myocardial revascularization using bilateral
      internal thoracic arteries in diabetic patients: a single centre experience.
AB  - OBJECTIVES: The use of bilateral internal thoracic arteries (BITAs) grafting has
      been documented to be advantageous over left internal thoracic artery (LITA)
      grafting. It has been shown to significantly improve clinical outcomes and
      increase long-term survival in patients with diabetes. However, harvesting BITAs
      may result in a greater risk of superficial wound infection (SWI) or deep sternal
      wound infection (DSWI) and cardiovascular complications (major adverse cardiac
      and cerebrovascular events; MACCE) in such a patient group. The objective of this
      study was to compare the incidence of SWI or DSWI and cardiovascular events in a
      series of isolated coronary artery bypass grafting (CABG) patients who underwent
      BITA grafting vs LITA grafting. METHODS: A total of 147 patients with coronary
      artery disease and diabetes underwent isolated CABG at John Paul II Hospital. Of
      these, 38 procedures were performed using BITA grafting and 109 with LITA
      saphenous vein grafting. RESULTS: MACCE were similar in bilateral groups (7.9%-
      BITA group and 9.2%--LITA group). No significant difference was found in
      mortality and length of stay between bilateral groups. The MACCE risk factor was
      age. The incidence of SWI and DSWI and sternal re-fixation did not differ between
      the BITA or LITA groups (5.2 vs 9.1%, 5.2 vs 7.3% and 5.2 vs 6.4%). The risk
      factors for DSWI were age (odds ratio 3.47, P = 0.032 for every 10 years) and
      body mass index >30 kg/m(2). CONCLUSIONS: Perioperative complications do not
      increase with the use of BITAs in this group of diabetic patients. There are no
      statistically significant differences in the number of superficial or deep wound
      infections or number of sternal resuturing between the BITA and LITA groups.

PMID- 22997250
TI  - Plasma brain natriuretic peptide as a biomarker for haemodynamic outcome and
      mortality following pulmonary endarterectomy for chronic thromboembolic pulmonary
      hypertension.
AB  - OBJECTIVES: In chronic thromboembolic pulmonary hypertension (CTEPH), right
      ventricular (RV) dysfunction is associated with increased morbidity and mortality
      following pulmonary endarterectomy. Plasma brain natriuretic peptide (BNP) levels
      were previously shown to correlate with RV (dys)function. We hypothesized that
      BNP can be used as a non-invasive biomarker to identify patients at 'high risk'
      for postoperative morbidity and mortality. METHODS: We studied the postoperative
      outcome in 73 consecutive patients. Patients were divided into three groups based
      on previously determined cut-off levels: BNP <11.5, indicating normal RV function
      (ejection fraction [EF] >=45%), BNP >48.5 pmol/l, indicating RV dysfunction
      (right ventricular ejection fraction <30%) and BNP 11.5-48.5 pmol/l.
      Postoperative 'bad outcome' was defined as the presence of either residual
      pulmonary hypertension (PH) or (all-cause) mortality. RESULTS: Plasma BNP >48.5
      pmol/l was shown to be an independent predictor of 'bad outcome'. Compared with
      BNP <11.5 pmol/l, BNP >48.5 pmol/l identified patients at higher risk for (all
      cause) mortality (17 vs 0%; P = 0.009) and residual PH (56 vs 20%; P < 0.004).
      Also, the durations of mechanical ventilation and intensive care unit stay were
      significantly longer in patients with BNP >48.5 pmol/ml. CONCLUSIONS: Plasma BNP
      levels may be of use as a non-invasive biomarker reflecting RV dysfunction, next
      to other well-recognized (invasive) parameters, for better preoperative risk
      stratification of CTEPH patients.

PMID- 22997251
TI  - Surgery on unfavourable persistent N2/N3 non-small-cell lung cancer after
      trimodal therapy: do the results justify the risk?
AB  - OBJECTIVES: Persistent mediastinal lymph node metastasis after neoadjuvant
      therapy is a significant negative indicator for survival. Even though there is
      still no consensus on the matter, some authors advocate a thorough restaging
      prior to surgery and deny surgery in cases of persistent N2 because of the poor
      outcome. We analysed our results after trimodal therapy in pN2/N3 stage III non
      small-cell lung cancer (NSCLC) and persistent mediastinal lymph node metastasis
      after neoadjuvant chemoradiotherapy. METHODS: We conducted a retrospective cohort
      analysis of 167 patients who received trimodal therapy for stage III NSCLC.
      Progression-free interval and survival were calculated. T-stage, N-stage, ypT
      stage, ypN2/3-stage and surgical procedure were tested as risk factors. RESULTS:
      Eighty-three patients with potentially resectable initial pN2/3 underwent 44
      pneumonectomies and 76% extended resections. Thirty-five patients showed
      persistent mediastinal lymph node metastasis after trimodal therapy. Treatment
      related comorbidity after an operative therapy was 58%. Hospital mortality was
      2.4%. The ypT- and ypN2/N3 stages were significant risk factors and, in the case
      of persistent mediastinal lymph node metastasis, median progression-free period
      was 17 months and median survival time was 21 months. CONCLUSIONS: Persistent but
      resectable N2/N3 after chemoradiotherapy in stage III NSCLC is the least
      favourable subgroup of patients in neoadjuvant approaches. If surgery can be
      carried out with curative intent and low morbidity, completing trimodal therapy
      is justified, with an acceptable outcome.

PMID- 22997252
TI  - Striatin-dependent membrane estrogen receptor signaling and vasoprotection by
      estrogens.

PMID- 22997253
TI  - Rapid estrogen receptor signaling is essential for the protective effects of
      estrogen against vascular injury.
AB  - BACKGROUND: Clinical trial and epidemiological data support that the
      cardiovascular effects of estrogen are complex, including a mixture of both
      potentially beneficial and harmful effects. In animal models, estrogen protects
      females from vascular injury and inhibits atherosclerosis. These effects are
      mediated by estrogen receptors (ERs), which, when bound to estrogen, can bind to
      DNA to directly regulate transcription. ERs can also activate several cellular
      kinases by inducing a rapid nonnuclear signaling cascade. However, the biological
      significance of this rapid signaling pathway has been unclear. METHODS AND
      RESULTS: In the present study, we develop a novel transgenic mouse in which rapid
      signaling is blocked by overexpression of a peptide that prevents ERs from
      interacting with the scaffold protein striatin (the disrupting peptide mouse).
      Microarray analysis of ex vivo treated mouse aortas demonstrates that rapid ER
      signaling plays an important role in estrogen-mediated gene regulatory responses.
      Disruption of ER-striatin interactions also eliminates the ability of estrogen to
      stimulate cultured endothelial cell migration and to inhibit cultured vascular
      smooth muscle cell growth. The importance of these findings is underscored by in
      vivo experiments demonstrating loss of estrogen-mediated protection against
      vascular injury in the disrupting peptide mouse after carotid artery wire injury.
      CONCLUSIONS: Taken together, these results support the concept that rapid,
      nonnuclear ER signaling contributes to the transcriptional regulatory functions
      of ER and is essential for many of the vasoprotective effects of estrogen. These
      findings also identify the rapid ER signaling pathway as a potential target for
      the development of novel therapeutic agents.

PMID- 22997254
TI  - Deficiency of the calcium-sensing receptor in the kidney causes parathyroid
      hormone-independent hypocalciuria.
AB  - Rare loss-of-function mutations in the calcium-sensing receptor (Casr) gene lead
      to decreased urinary calcium excretion in the context of parathyroid hormone
      (PTH)-dependent hypercalcemia, but the role of Casr in the kidney is unknown.
      Using animals expressing Cre recombinase driven by the Six2 promoter, we
      generated mice that appeared grossly normal but had undetectable levels of Casr
      mRNA and protein in the kidney. Baseline serum calcium, phosphorus, magnesium,
      and PTH levels were similar to control mice. When challenged with dietary calcium
      supplementation, however, these mice had significantly lower urinary calcium
      excretion than controls (urinary calcium to creatinine, 0.31+/-0.03 versus 0.63+/
      0.14; P=0.001). Western blot analysis on whole-kidney lysates suggested an
      approximately four-fold increase in activated Na(+)-K(+)-2Cl(-) cotransporter
      (NKCC2). In addition, experimental animals exhibited significant downregulation
      of Claudin14, a negative regulator of paracellular cation permeability in the
      thick ascending limb, and small but significant upregulation of Claudin16, a
      positive regulator of paracellular cation permeability. Taken together, these
      data suggest that renal Casr regulates calcium reabsorption in the thick
      ascending limb, independent of any change in PTH, by increasing the lumen
      positive driving force for paracellular Ca(2+) transport.

PMID- 22997255
TI  - PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis.
AB  - Urinary excretion of lipocalin-type PGD(2) synthase (L-PGDS), which converts PG
      H(2) to PGD(2), increases in early diabetic nephropathy. In addition, L-PGDS
      expression in the tubular epithelium increases in adriamycin-induced nephropathy,
      suggesting that locally produced L-PGDS may promote the development of CKD. In
      this study, we found that L-PGDS-derived PGD(2) contributes to the progression of
      renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse
      model, the tubular epithelium synthesized L-PGDS de novo after unilateral
      ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both
      exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the
      cortex, and decreased production of the Th2 cytokines IL-4 and IL-13.
      Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after
      UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13
      also ameliorated renal fibrosis in the UUO kidney. Taken together, these data
      suggest that blocking the activation of CRTH2 by PGD(2) might be a strategy to
      slow the progression of renal fibrosis in CKD.

PMID- 22997256
TI  - Uromodulin triggers IL-1beta-dependent innate immunity via the NLRP3
      inflammasome.
AB  - Uromodulin/Tamm-Horsfall protein is not immunostimulatory in the tubular lumen,
      but through unknown mechanisms it can activate dendritic cells and promote
      inflammation in the renal interstitium. Here, we noted that uromodulin isolated
      from human urine aggregates to large, irregular clumps with a crystal-like
      ultrastructure. These uromodulin nanoparticles activated isolated human monocytes
      to express costimulatory molecules and to secrete the mature proinflammatory
      cytokines, including IL-1beta. Full release of IL-1beta in response to uromodulin
      depended on priming of pro-IL-1beta expression by Toll-like receptors, TNF-alpha,
      or IL-1alpha. In addition, uromodulin-induced secretion of mature IL-1beta
      depended on the NLRP3 inflammasome, its linker molecule ASC, and pro-IL-1beta
      cleavage by caspase-1. Activation of NLRP3 required phagocytosis of uromodulin
      particles into lysosomes, cathepsin leakage, oxidative stress, and potassium
      efflux from the cell. Taken together, these data suggest that uromodulin is a
      NLRP3 agonist handled by antigen-presenting cells as an immunostimulatory
      nanoparticle. Thus, in the presence of tubular damage that exposes the renal
      interstitium, uromodulin becomes an endogenous danger signal. The inability of
      renal parenchymal cells to secrete IL-1beta may explain why uromodulin remains
      immunologically inert inside the luminal compartment of the urinary tract.

PMID- 22997258
TI  - Multiphoton imaging of the glomerular permeability of angiotensinogen.
AB  - Patients and animals with renal injury exhibit increased urinary excretion of
      angiotensinogen. Although increased tubular synthesis of angiotensinogen
      contributes to the increased excretion, we do not know to what degree glomerular
      filtration of systemic angiotensinogen, especially through an abnormal glomerular
      filtration barrier, contributes to the increase in urinary levels. Here, we used
      multiphoton microscopy to visualize and quantify the glomerular permeability of
      angiotensinogen in the intact mouse and rat kidney. In healthy mice and Munich
      Wistar-Fromter rats at the early stage of glomerulosclerosis, the glomerular
      sieving coefficient of systemically infused Atto565-labeled human angiotensinogen
      (Atto565-hAGT), which rodent renin cannot cleave, was only 25% of the glomerular
      sieving coefficient of albumin, and its urinary excretion was undetectable. In a
      more advanced phase of kidney disease, the glomerular permeability of Atto565
      hAGT was slightly higher but still very low. Furthermore, unlike urinary albumin,
      the significantly higher urinary excretion of endogenous rat angiotensinogen did
      not correlate with either the Atto565-hAGT or Atto565-albumin glomerular sieving
      coefficients. These results strongly suggest that the vast majority of urinary
      angiotensinogen originates from the tubules rather than glomerular filtration.

PMID- 22997259
TI  - Mechanisms of light chain injury along the tubular nephron.
AB  - The tubular nephron is responsible for reabsorption and catabolism of filtered
      low molecular weight proteins that include Ig free light chains. In the setting
      of a plasma cell dyscrasia, significant amounts of free light chains, now
      monoclonal proteins, present to the tubular nephron for disposal. The result may
      be clinical renal dysfunction in the form of AKI, progressive CKD, and end-stage
      kidney disease. Here, I review the mechanisms involved in these processes that
      result in tubular injury, including proximal tubulopathy and cast nephropathy.

PMID- 22997257
TI  - eNOS deficiency predisposes podocytes to injury in diabetes.
AB  - Endothelial nitric oxide synthase (eNOS) deficiency may contribute to the
      pathogenesis of diabetic nephropathy in both experimental models and humans, but
      the underlying mechanism is not fully understood. Here, we studied two common
      sequelae of endothelial dysfunction in diabetes: glomerular capillary growth and
      effects on neighboring podocytes. Streptozotocin-induced diabetes increased
      glomerular capillary volume in both C57BL/6 and eNOS(-/-) mice. Inhibiting the
      vascular endothelial growth factor receptor attenuated albuminuria in diabetic
      C57BL/6 mice but not in diabetic eNOS(-/-) mice, even though it inhibited
      glomerular capillary enlargement in both. In eNOS(-/-) mice, an acute
      podocytopathy and heavy albuminuria occurred as early as 2 weeks after inducing
      diabetes, but treatment with either captopril or losartan prevented these
      effects. In vitro, serum derived from diabetic eNOS(-/-) mice augmented actin
      filament rearrangement in cultured podocytes. Furthermore, conditioned medium
      derived from eNOS(-/-) glomerular endothelial cells exposed to both high glucose
      and angiotensin II activated podocyte RhoA. Taken together, these results suggest
      that the combined effects of eNOS deficiency and hyperglycemia contribute to
      podocyte injury, highlighting the importance of communication between endothelial
      cells and podocytes in diabetes. Identifying mediators of this communication may
      lead to the future development of therapies targeting endothelial dysfunction in
      albuminuric individuals with diabetes.

PMID- 22997260
TI  - Treatment of primary FSGS in adults.
AB  - Over the last 20 years, primary FSGS has emerged as one of the leading causes of
      idiopathic nephrotic syndrome in adults, particularly among African Americans. In
      nephrotic patients, progression to ESRD often occurs over the course of 5-10
      years, whereas non-nephrotic patients and those entering a remission have an
      extremely favorable prognosis. As a result, it is in patients who remain
      persistently nephrotic despite conservative therapy that a more aggressive
      therapeutic approach is taken. Primary FSGS was once considered an entity
      nonresponsive to prednisone or immunosuppressive agents, but it has become
      apparent over the last 20 years that a substantial portion of nephrotic adults
      with primary FSGS do respond to treatment with a significantly improved
      prognosis. The recent histologic classification proposed for FSGS has provided
      additional insights into the prognosis and response to therapy. This article
      reviews the current knowledge regarding the presentation, prognosis, and
      therapeutic approach in adults with primary FSGS.

PMID- 22997261
TI  - The placental origins of sudden cardiac death.
AB  - OBJECTIVE: Most sudden cardiac deaths are due to cardiac arrhythmias, and
      abnormalities in the autonomic nervous system could underlie them. There is
      growing evidence that coronary heart disease is associated with alterations of
      fetal development as a result of variations in the processes of placentation that
      control fetal nutrition. We hypothesized that placental size would be associated
      with sudden cardiac death. METHODS: We examined sudden cardiac death within the
      Helsinki Birth Cohort of 13 345 men and women. RESULTS: One hundred eighty-seven
      (2.7%) men and 47 (0.7%) women had sudden unexplained cardiac death outside
      hospital. Sudden death was associated with a thin placenta, the hazard ratio
      being 1.47 [95% confidence interval (CI) 1.11-1.93, P = 0.006] for each g/cm(2)
      decrease in thickness. Sudden death was independently associated with poor
      educational attainment (P < 0.0001). Both of these associations were independent
      of socio-economic status in later life. CONCLUSION: Sudden death may be initiated
      by impaired development of the autonomic nervous system in utero as a result of
      shallow invasion of the spiral arteries in the maternal endometrium and
      consequent fetal malnutrition.

PMID- 22997262
TI  - The effect of sample holder geometry on electromagnetic heating of nanoparticle
      and NaCl solutions at 13.56 MHz.
AB  - Electromagnetic absorption and subsequent heating of nanoparticle solutions and
      simple NaCl ionic solutions is examined for biomedical applications in the
      radiofrequency range at 13.56 MHz. It is shown via both theory and experiment
      that for in vitro measurements the shape of the solution container plays a major
      role in absorption and heating.

PMID- 22997263
TI  - Recursive algorithms for bias and gain nonuniformity correction in infrared
      videos.
AB  - Infrared focal-plane array (IRFPA) detectors suffer from fixed-pattern noise
      (FPN) that degrades image quality, which is also known as spatial nonuniformity.
      FPN is still a serious problem, despite recent advances in IRFPA technology. This
      paper proposes new scene-based correction algorithms for continuous compensation
      of bias and gain nonuniformity in FPA sensors. The proposed schemes use recursive
      least-square and affine projection techniques that jointly compensate for both
      the bias and gain of each image pixel, presenting rapid convergence and
      robustness to noise. The synthetic and real IRFPA videos experimentally show that
      the proposed solutions are competitive with the state-of-the-art in FPN
      reduction, by presenting recovered images with higher fidelity.

PMID- 22997264
TI  - Clustered-dot halftoning with direct binary search.
AB  - In this paper, we present a new algorithm for aperiodic clustered-dot halftoning
      based on direct binary search (DBS). The DBS optimization framework has been
      modified for designing clustered-dot texture, by using filters with different
      sizes in the initialization and update steps of the algorithm. Following an
      intuitive explanation of how the clustered-dot texture results from this modified
      framework, we derive a closed-form cost metric which, when minimized,
      equivalently generates stochastic clustered-dot texture. An analysis of the cost
      metric and its influence on the texture quality is presented, which is followed
      by a modification to the cost metric to reduce computational cost and to make it
      more suitable for screen design.

PMID- 22997265
TI  - Generalized inverse-approach model for spectral-signal recovery.
AB  - We have studied the transformation system of a spectral signal to the response of
      the system as a linear mapping from higher to lower dimensional space in order to
      look more closely at inverse-approach models. The problem of spectral-signal
      recovery from the response of a transformation system is generally stated on the
      basis of the generalized inverse-approach theorem, which provides a modular model
      for generating a spectral signal from a given response value. The controlling
      criteria, including the robustness of the inverse model to perturbations of the
      response caused by noise, and the condition number for matrix inversion, are
      proposed, together with the mean square error, so as to create an efficient model
      for spectral-signal recovery. The spectral-reflectance recovery and color
      correction of natural surface color are numerically investigated to appraise
      different illuminant-observer transformation matrices based on the proposed
      controlling criteria both in the absence and the presence of noise.

PMID- 22997266
TI  - Spatio-temporal auxiliary particle filtering with l1-norm-based appearance model
      learning for robust visual tracking.
AB  - In this paper, we propose an efficient and accurate visual tracker equipped with
      a new particle filtering algorithm and robust subspace learning-based appearance
      model. The proposed visual tracker avoids drifting problems caused by abrupt
      motion changes and severe appearance variations that are well-known difficulties
      in visual tracking. The proposed algorithm is based on a type of auxiliary
      particle filtering that uses a spatio-temporal sliding window. Compared to
      conventional particle filtering algorithms, spatio-temporal auxiliary particle
      filtering is computationally efficient and successfully implemented in visual
      tracking. In addition, a real-time robust principal component pursuit (RRPCP)
      equipped with  l(1)-norm optimization has been utilized to obtain a new
      appearance model learning block for reliable visual tracking especially for
      occlusions in object appearance. The overall tracking framework based on the dual
      ideas is robust against occlusions and out-of-plane motions because of the
      proposed spatio-temporal filtering and recursive form of RRPCP. The designed
      tracker has been evaluated using challenging video sequences, and the results
      confirm the advantage of using this tracker.

PMID- 22997267
TI  - Manifold regularized multitask learning for semi-supervised multilabel image
      classification.
AB  - It is a significant challenge to classify images with multiple labels by using
      only a small number of labeled samples. One option is to learn a binary
      classifier for each label and use manifold regularization to improve the
      classification performance by exploring the underlying geometric structure of the
      data distribution. However, such an approach does not perform well in practice
      when images from multiple concepts are represented by high-dimensional visual
      features. Thus, manifold regularization is insufficient to control the model
      complexity. In this paper, we propose a manifold regularized multitask learning
      (MRMTL) algorithm. MRMTL learns a discriminative subspace shared by multiple
      classification tasks by exploiting the common structure of these tasks. It
      effectively controls the model complexity because different tasks limit one
      another's search volume, and the manifold regularization ensures that the
      functions in the shared hypothesis space are smooth along the data manifold. We
      conduct extensive experiments, on the PASCAL VOC'07 dataset with 20 classes and
      the MIR dataset with 38 classes, by comparing MRMTL with popular image
      classification algorithms. The results suggest that MRMTL is effective for image
      classification.

PMID- 22997268
TI  - Linear distance coding for image classification.
AB  - The feature coding-pooling framework is shown to perform well in image
      classification tasks, because it can generate discriminative and robust image
      representations. The unavoidable information loss incurred by feature
      quantization in the coding process and the undesired dependence of pooling on the
      image spatial layout, however, may severely limit the classification. In this
      paper, we propose a linear distance coding (LDC) method to capture the
      discriminative information lost in traditional coding methods while
      simultaneously alleviating the dependence of pooling on the image spatial layout.
      The core of the LDC lies in transforming local features of an image into more
      discriminative distance vectors, where the robust image-to-class distance is
      employed. These distance vectors are further encoded into sparse codes to capture
      the salient features of the image. The LDC is theoretically and experimentally
      shown to be complementary to the traditional coding methods, and thus their
      combination can achieve higher classification accuracy. We demonstrate the
      effectiveness of LDC on six data sets, two of each of three types (specific
      object, scene, and general object), i.e., Flower 102 and PFID 61, Scene 15 and
      Indoor 67, Caltech 101 and Caltech 256. The results show that our method
      generally outperforms the traditional coding methods, and achieves or is
      comparable to the state-of-the-art performance on these data sets.

PMID- 22997269
TI  - What are we tracking: a unified approach of tracking and recognition.
AB  - Tracking is essentially a matching problem. While traditional tracking methods
      mostly focus on low-level image correspondences between frames, we argue that
      high-level semantic correspondences are indispensable to make tracking more
      reliable. Based on that, a unified approach of low-level object tracking and high
      level recognition is proposed for single object tracking, in which the target
      category is actively recognized during tracking. High-level offline models
      corresponding to the recognized category are then adaptively selected and
      combined with low-level online tracking models so as to achieve better tracking
      performance. Extensive experimental results show that our approach outperforms
      state-of-the-art online models in many challenging tracking scenarios such as
      drastic view change, scale change, background clutter, and morphable objects.

PMID- 22997270
TI  - Exemplar-based image inpainting using multiscale graph cuts.
AB  - We present a novel formulation of exemplar-based inpainting as a global energy
      optimization problem, written in terms of the offset map. The proposed energy
      function combines a data attachment term that ensures the continuity of
      reconstruction at the boundary of the inpainting domain with a smoothness term
      that ensures a visually coherent reconstruction inside the hole. This formulation
      is adapted to obtain a global minimum using the graph cuts algorithm. To reduce
      the computational complexity, we propose an efficient multiscale graph cuts
      algorithm. To compensate the loss of information at low resolution levels, we use
      a feature representation computed at the original image resolution. This permits
      alleviation of the ambiguity induced by comparing only color information when the
      image is represented at low resolution levels. Our experiments show how well the
      proposed algorithm performs compared with other recent algorithms.

PMID- 22997271
TI  - Fuzzy Complex Dynamical Networks and Its Synchronization.
AB  - In this paper, the robust synchronization problem of fuzzy complex dynamical
      networks is investigated. A fuzzy complex dynamical network is an extension to an
      uncertain complex dynamical network in which all sources of parametric
      uncertainties are modeled with fuzzy numbers, i.e., all nodes' dynamics are
      described by fuzzy differential equations (FDEs) that permit a better description
      of a real process occurring in the presence of inaccuracy. To resolve the
      synchronization problem, this paper introduces new adaptive and impulsive
      controllers in which globally exponential synchronization of fuzzy dynamical
      networks under easily verified conditions is guaranteed. Moreover, we propose an
      efficient method that helps to find certain suitable nodes to be impulsively
      controlled via pinning, noting that these nodes, in general, vary at distinct
      impulsive time instants. Therefore, by using adaptive controllers and applying
      impulsive controllers to only a small portion of nodes, the whole network will
      completely be synchronized to a certain objective state. Finally, two numerical
      examples are given to illustrate the effectiveness of the proposed controllers. 

PMID- 22997272
TI  - Image Cosegmentation by Incorporating Color Reward Strategy and Active Contour
      Model.
AB  - The design of robust and efficient cosegmentation algorithms is challenging
      because of the variety and complexity of the objects and images. In this paper,
      we propose a new cosegmentation model by incorporating a color reward strategy
      and an active contour model. A new energy function corresponding to the curve is
      first generated with two considerations: the foreground similarity between the
      image pairs and the background consistency in each of the image pair.
      Furthermore, a new foreground similarity measurement based on the rewarding
      strategy is proposed. Then, we minimize the energy function value via a mutual
      procedure which uses dynamic priors to mutually evolve the curves. The proposed
      method is evaluated on many images from commonly used databases. The experimental
      results demonstrate that the proposed model can efficiently segment the common
      objects from the image pairs with generally lower error rate than many existing
      and conventional cosegmentation methods. 

PMID- 22997273
TI  - On modeling and state estimation for genetic regulatory networks with polytopic
      uncertainties.
AB  - It is widely believed that gene expression data contains rich information that
      could discover the higher-order structures of an organism and even interpret its
      behavior. The modeling problem of gene regulatory networks (GRNs) from the
      experimental data has recently received increasing research attention. In this
      paper, we investigate the uncertainty quantification and state estimation issues.
      The polytopic uncertainty model (PUM) is exploited for describing the GRNs where
      the parameter uncertainties are constrained in a convex polytope domain. To cope
      with the high-dimension problem for GRN models, the principal component plane
      (PCP) algorithm is proposed to construct a pruned polytope in order to use as
      less vertices as possible to maintain the essential information from original
      polytope. The so-called system equivalence transformation is developed to
      transform the original system into a simpler canonical form and therefore
      facilitate the subsequent state estimation problem. For the state estimation
      problem, a robust stability condition is incorporated with guaranteed H2
      performance via the semi-definite programme method, and then a new sufficient
      condition is derived for the desired H2 estimators with several free slack
      matrices. Such a condition is vertex-dependent and therefore possesses less
      conservatism. It is shown, via simulation from real-world microarray time-series
      data, that the designed H2 estimators have strong capability of dealing with
      modeling and estimation problems for short but high-dimensional gene expression
      time series.

PMID- 22997274
TI  - Extracting gene-gene interactions through curve fitting.
AB  - This paper presents a simple and novel curve fitting approach for generating
      simple gene regulatory subnetworks from time series gene expression data.
      Microarray experiments simultaneously generate massive data sets and help
      immensely in the large-scale study of gene expression patterns. Initial
      biclustering reduces the search space in the high-dimensional microarray data.
      The least-squares error between fitting of gene pairs is minimized to extract a
      set of gene-gene interactions, involving transcriptional regulation of genes. The
      higher error values are eliminated to retain only the strong interacting gene
      pairs in the resultant gene regulatory subnetwork. Next the algorithm is extended
      to a generalized framework to enhance its capability. The methodology takes care
      of the higher-order dependencies involving multiple genes co-regulating a single
      gene, while eliminating the need for user-defined parameters. It has been applied
      to the time-series Yeast data, and the experimental results biologically
      validated using standard databases and literature.

PMID- 22997275
TI  - Large abdominal photopenic area on 99mTc-sestamibi myocardial perfusion imaging.
AB  - (99m)Tc-sestamibi myocardial perfusion imaging is frequently performed in
      conjunction with exercise or pharmacologic stress testing for evaluation of
      coronary heart disease. Interpretation of these studies includes systematic
      review of unprocessed rotating projectional images for evaluation of cardiac size
      as well as the presence of motion or attenuation artifacts. Occasionally,
      incidental noncardiac findings are detected on review of the projectional images.
      We report a case of a patient with a history of autosomal dominant polycystic
      kidney disease who was found to have a large abdominal photopenic area on the
      projectional images. The photopenic area corresponded to the location of large
      intraabdominal cysts on abdominal CT and was consistent with hepatic cysts
      associated with the patient's known polycystic kidney disease. We review the
      differential diagnosis of large abdominal photopenic regions identified on
      myocardial projectional images and the importance of routinely analyzing these
      images for incidental noncardiac findings.

PMID- 22997276
TI  - Wandering kidney in dual-kidney transplant recipient presents a pitfall in the
      interpretation of renal scintigraphy.
AB  - A 26-y-old patient with end-stage renal disease and recent dual transplantation
      of cadaveric kidneys en bloc presented with increasing abdominal pain and a
      rising level of serum creatinine. An anterior-view (99m)Tc
      mercaptoacetyltriglycine renogram demonstrated the typical overlap of the lower
      pole of the superior kidney and the upper pole of the inferior kidney. The
      renogram was consistent with vasomotor nephropathy. Subsequent imaging 1 wk later
      for worsening symptoms demonstrated a single reniform structure in the expected
      location of the inferior transplanted kidney, which was interpreted as a loss of
      perfusion to the superior kidney. Correlation with subsequent CT and sonography
      showed normal perfusion to both transplanted kidneys and that the superior kidney
      had wandered inferiorly, completely overlapping the inferior kidney on the
      anterior projection. The increasing prevalence of dual kidney transplantation
      warrants special attention to the potential for a wandering kidney.

PMID- 22997277
TI  - Engineering and performance (NEMA and animal) of a lower-cost higher-resolution
      animal PET/CT scanner using photomultiplier-quadrant-sharing detectors.
AB  - The dedicated murine PET (MuPET) scanner is a high-resolution, high-sensitivity,
      and low-cost preclinical PET camera designed and manufactured at our laboratory.
      In this article, we report its performance according to the NU 4-2008 standards
      of the National Electrical Manufacturers Association (NEMA). We also report the
      results of additional phantom and mouse studies. METHODS: The MuPET scanner,
      which is integrated with a CT camera, is based on the photomultiplier-quadrant
      sharing concept and comprises 180 blocks of 13 * 13 lutetium yttrium
      oxyorthosilicate crystals (1.24 * 1.4 * 9.5 mm(3)) and 210 low-cost 19-mm
      photomultipliers. The camera has 78 detector rings, with an 11.6-cm axial field
      of view and a ring diameter of 16.6 cm. We measured the energy resolution,
      scatter fraction, sensitivity, spatial resolution, and counting rate performance
      of the scanner. In addition, we scanned the NEMA image-quality phantom, Micro
      Deluxe and Ultra-Micro Hot Spot phantoms, and 2 healthy mice. RESULTS: The system
      average energy resolution was 14% at 511 keV. The average spatial resolution at
      the center of the field of view was about 1.2 mm, improving to 0.8 mm and
      remaining below 1.2 mm in the central 6-cm field of view when a resolution
      recovery method was used. The absolute sensitivity of the camera was 6.38% for an
      energy window of 350-650 keV and a coincidence timing window of 3.4 ns. The
      system scatter fraction was 11.9% for the NEMA mouselike phantom and 28% for the
      ratlike phantom. The maximum noise-equivalent counting rate was 1,100 at 57 MBq
      for the mouselike phantom and 352 kcps at 65 MBq for the ratlike phantom. The 1
      mm fillable rod was clearly observable using the NEMA image-quality phantom. The
      images of the Ultra-Micro Hot Spot phantom also showed the 1-mm hot rods. In the
      mouse studies, both the left and right ventricle walls were clearly observable,
      as were the Harderian glands. CONCLUSION: The MuPET camera has excellent
      resolution, sensitivity, counting rate, and imaging performance. The data show it
      is a powerful scanner for preclinical animal study and pharmaceutical
      development.

PMID- 22997279
TI  - Gas chromatography-tandem mass spectrometry method for the simultaneous
      determination of oxysterols, plant sterols, and cholesterol precursors.
AB  - BACKGROUND: Cholesterol precursors and plant sterols have considerable potential
      as plasma biomarkers in several disorders of sterol metabolism and intestinal
      sterol absorption. Oxysterols are associated with atherogenesis,
      neurodegeneration, and inflammation. We developed a GC-MS method for the
      simultaneous analysis of these species in human plasma, including 24-, 25-, 27
      hydroxycholesterol; 7-ketocholesterol; lanosterol; lathosterol; 7
      dehydrocholesterol; desmosterol; stigmasterol; sitosterol; and campesterol.
      METHODS: Sterols were hydrolyzed with ethanolic potassium hydroxide solution,
      extracted by liquid/liquid extraction with n-hexane, and derivatized with N
      methyl-N-trimethylsilyl-trifluoracetamide. Positive chemical ionization with
      ammonia, as reagent gas, was applied to generate high abundant precursor ions.
      RESULTS: The definition of highly sensitive precursor/product ion transitions,
      especially for coeluting substances, allowed fast gas chromatography run times of
      under 8.5 min. Using the multiple reaction monitoring mode, detection limits in
      the picogram per milliliter range could be achieved for most compounds. The
      method was validated for precision and recovery. Intraassay and interassay CVs
      were mostly <15% for serum and plasma samples. The recoveries of supplemented
      plasma samples in different concentrations were 88%-117%. The method was applied
      to stratification of patients with disorders in cholesterol biosynthesis and/or
      cholesterol absorption in hypercholesterolemia. The method revealed associations
      of sterol species with thyroid dysfunction and type 2 diabetes. CONCLUSIONS: This
      method allows high-throughput sterol profiling in various diseases.

PMID- 22997278
TI  - Methadone maintenance treatment in China: perceived challenges from the
      perspectives of service providers and patients.
AB  - BACKGROUND: China has recently adopted methadone maintenance treatment (MMT) as a
      national strategy to address the problem of drug abuse and related public health
      issues such as HIV and HCV infections. However, low enrollment and retention
      rates suggest that barriers may exist in MMT utilization. This study examined
      both patients' perceptions and service providers' perceptions of challenges in
      MMT implementation in China. METHODS: Four focus groups were conducted in two
      Chinese cities, Shanghai and Kunming, to explore the perceived and experienced
      barriers in MMT participation in China. All focus group discussions with
      participants were audio taped and transcribed. Atlas.ti 5.1 was used to analyze
      data. RESULTS: Service providers and patient participants reported positive
      experiences (e.g. effects of MMT in curbing withdrawal symptoms) but also
      expressed concerns about side effects and continued heroin use during MMT. They
      also identified barriers in participating and remaining in MMT, including
      affordability (fee requirement), acceptability (methadone as a substitution,
      dose, long-term nature), accommodation and accessibility (inconvenient operation
      hours, lack of transferability to other MMT clinics during travel) and
      competition between public health and public security. CONCLUSIONS: The present
      findings have implications for reconsidering the current MMT policies and
      practices in order to improve access, utilization and, ultimately, the
      effectiveness of MMT in China.

PMID- 22997281
TI  - Troponin I measured by a high-sensitivity assay in patients with suspected
      reversible myocardial ischemia: data from the Akershus Cardiac Examination (ACE)
      1 study.
AB  - BACKGROUND: Whether cardiac troponin concentrations are increased by reversible
      myocardial ischemia is controversial. Differences in the structure of cardiac
      troponin I (cTnI) and cTnT may have implications for diagnostic utility. METHODS:
      cTnI was measured with a prototype high-sensitivity (hs) assay in 198 patients
      referred for myocardial perfusion imaging (MPI) before exercise stress testing,
      immediately after, and 1.5 and 4.5 h later. We categorized patients according to
      MPI results and compared hs-cTnI concentrations with hs-cTnT concentrations.
      RESULTS: Baseline hs-cTnI was higher in patients with reversible myocardial
      ischemia (n = 19) vs the other patients (n = 179): median 4.4 (quartiles 1-3: 2.3
      7.1) vs 2.5 (1.4-4.3) ng/L, P = 0.003. Baseline hs-cTnI and hs-cTnT
      concentrations were correlated (r = 0.46, P < 0.001) and the areas under the ROC
      curve for hs-cTnI and hs-cTnT in diagnosing reversible ischemia were similar:
      0.71 vs 0.69, P = 0.77. Whereas hs-cTnI increased immediately after exercise (P <
      0.001 vs baseline measurements) in patients without ischemia, it increased after
      4.5 h in patients with reversible ischemia (P = 0.01). The increment in hs-cTnI
      concentrations was comparable between groups; thus, measuring hs-cTnI after
      exercise stress testing did not improve diagnostic accuracy over baseline
      measurements, and hs-cTnI concentrations were not found to be associated with
      reversible myocardial ischemia in multivariate analysis. By linear regression
      analysis, age, male sex, history of hypertension, angiotensin-converting enzyme
      inhibitor use, and lower left ventricular ejection fraction were associated with
      higher baseline hs-cTnI concentrations. CONCLUSIONS: In patients referred to MPI,
      hs-cTnI concentrations were not closely associated with reversible myocardial
      ischemia, but rather were influenced by variables associated with structural
      alterations of the myocardium.

PMID- 22997280
TI  - Clinical and genetic correlates of growth differentiation factor 15 in the
      community.
AB  - BACKGROUND: Growth differentiation factor 15 (GDF15), a stress-responsive
      cytokine produced in cardiovascular cells under conditions of inflammation and
      oxidative stress, is emerging as an important prognostic marker in individuals
      with and without existing cardiovascular disease (CVD). We therefore examined the
      clinical and genetic correlates of circulating GDF15 concentrations, which have
      not been investigated collectively. METHODS: Plasma GDF15 concentrations were
      measured in 2991 participants in the Framingham Offspring Study who were free of
      clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of
      GDF15 were examined in multivariable analyses. We then conducted a genomewide
      association study of the GDF15 concentration that included participants in the
      Framingham Offspring Study and participants in the PIVUS (Prospective
      Investigation of the Vasculature in Uppsala Seniors) study. RESULTS: GDF15 was
      positively associated with age, smoking, antihypertensive treatment, diabetes,
      worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs),
      but it was negatively associated with total cholesterol and HDL cholesterol.
      Clinical correlates accounted for 38% of interindividual variation in the
      circulating GDF15 concentration, whereas genetic factors accounted for up to 38%
      of the residual variability (h(2) = 0.38; P = 2.5 * 10(-11)). We identified 1
      locus of genomewide significance. This locus, which is on chromosome 19p13.11 and
      includes the GDF15 gene, is associated with GDF15 concentration (smallest P =
      2.74 * 10(-32) for rs888663). Conditional analyses revealed 2 independent
      association signals at this locus (rs888663 and rs1054564), which were associated
      with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory
      individuals, both cardiometabolic risk factors and genetic factors play important
      roles in determining circulating GDF15 concentrations and contribute similarly to
      the overall variation.

PMID- 22997282
TI  - Biomarker failures.

PMID- 22997283
TI  - Cardiac and inflammation biomarker profile after initiation of adjuvant
      trastuzumab therapy.

PMID- 22997284
TI  - Psychometric properties of the NEI-RQL-42 questionnaire in keratoconus.
AB  - PURPOSE: To assess the psychometric properties of the National Eye Institute
      Refractive Error Quality of Life (NEI-RQL-42) questionnaire in keratoconus and
      compare these findings to patients with refractive error correction alone.
      METHODS: The Portuguese version of the NEI-RQL-42 Quality of Life questionnaire
      was completed by 44 patients who had keratoconus before and after implantation of
      intracorneal ring segments. Rasch analysis was used to assess the use of response
      categories, success in measuring a single trait per subscale (unidimensionality),
      ability to discriminate person ability (precision), and targeting of questions to
      person quality of life (QoL). RESULTS: Rasch analysis was performed for the
      questionnaire subscales using stacked preoperative and postoperative data. Three
      subscales (Symptoms, Dependence on correction, and Suboptimal correction)
      contained response categories that were not used as intended. Six subscales
      contained misfitting items indicating multidimensionality. Eleven subscales
      exhibited inadequate measurement precision. Only the Near vision subscale
      demonstrated adequate precision with a person separation greater than 2.0.
      Targeting of items to person QoL was adequate in 11 of the 12 subscales with a
      mean item location of less than 1 logit. CONCLUSIONS: Only one NEI-RQL-42
      subscale (Near vision) performed adequately in keratoconus. Targeting was better
      in patients with keratoconus than in patients with refractive error correction
      alone, but 11 of the 12 subscales remain manifestly inadequate. Better
      instruments exist for measuring patient-reported outcomes in keratoconus.

PMID- 22997285
TI  - Functional morphometry of horizontal rectus extraocular muscles during horizontal
      ocular duction.
AB  - PURPOSE: We explored multiple quantitative measures of horizontal rectus
      extraocular muscle (EOM) morphology to determine the magnetic resonance imaging
      (MRI) measure best correlating with duction and thus contractility. METHODS:
      Surface coil coronal MRI was obtained in target-controlled central gaze and
      multiple positions of adduction and abduction in 26 orbits of 15 normal
      volunteers. Duction angles were determined by position changes of the globe-optic
      nerve junction. Cross-sectional areas, partial volumes, and location of peak
      cross-sections of the horizontal rectus EOMs were computed in contiguous image
      planes 2-mm thick spanning the EOM origins to the globe equator. RESULTS: All
      measures correlated significantly with duction angle (P < 0.0001). The best
      measures obtainable in single image planes were the maximum change in the cross
      sectional area between equivalent image planes, with coefficients of
      determination R(2) = 0.92 for medial rectus (MR) and 0.91 for lateral rectus
      (LR), and percentage change in maximum cross-section with R(2) = 0.79 for MR and
      0.78 for LR. The best partial volume measure of contractility was the change in
      partial volumes in four contiguous posterior planes (R(2) = 0.86 MR and for 0.89
      LR), particularly when combined with the corresponding change in partial volume
      for the antagonist EOM (R(2) = 0.95 for MR and LR). CONCLUSIONS: EOM morphologic
      changes are highly correlated with degrees of duction and thus contractility.
      Both changes in single-plane maximum cross-sectional areas and posterior partial
      volumes provide accurate, quantitative measures of EOM contractility.

PMID- 22997286
TI  - Binocular eye movement control and motion perception: what is being tracked?
AB  - PURPOSE: We investigated under what conditions humans can make independent slow
      phase eye movements. The ability to make independent movements of the two eyes
      generally is attributed to few specialized lateral eyed animal species, for
      example chameleons. In our study, we showed that humans also can move the eyes in
      different directions. To maintain binocular retinal correspondence independent
      slow phase movements of each eye are produced. METHODS: We used the scleral
      search coil method to measure binocular eye movements in response to
      dichoptically viewed visual stimuli oscillating in orthogonal direction. RESULTS:
      Correlated stimuli led to orthogonal slow eye movements, while the binocularly
      perceived motion was the vector sum of the motion presented to each eye. The
      importance of binocular fusion on independency of the movements of the two eyes
      was investigated with anti-correlated stimuli. The perceived global motion
      pattern of anti-correlated dichoptic stimuli was perceived as an oblique
      oscillatory motion, as well as resulted in a conjugate oblique motion of the
      eyes. CONCLUSIONS: We propose that the ability to make independent slow phase eye
      movements in humans is used to maintain binocular retinal correspondence. Eye-of
      origin and binocular information are used during the processing of binocular
      visual information, and it is decided at an early stage whether binocular or
      monocular motion information and independent slow phase eye movements of each eye
      are produced during binocular tracking.

PMID- 22997287
TI  - Lipid component contributions to the surface activity of meibomian lipids.
AB  - PURPOSE: Meibomian lipid films have very complex physical properties that enable
      them to be compressed and expanded without collapsing. These properties can be
      attributed to the self assembly of the individual components, mainly wax and
      cholesteryl esters (WE and CE). Here, the surface pressure properties of WEs and
      CEs films have been compared to evaluate their contributions to meibomian lipid
      films. METHODS: Films of different WEs and CEs were spread on a Langmuir trough
      and their surface pressure area profiles were compared with a particular emphasis
      on the effects caused by the degree of saturation of the alkyl/alkene chains.
      RESULTS: Fully saturated WEs and CEs formed unstable films that collapsed upon
      compression. Very unsaturated waxes and CEs tended to have two distinct phases,
      one that reflects interaction with the aqueous subphase, while the second
      appeared to be with the multilayered bulk of the lipid film. With aging of the
      films, the WEs tended to move off the surface into the bulk. When meibomian lipid
      films were seeded with large amounts of WEs, only minor changes could be seen
      unless the WE was very unsaturated. CONCLUSIONS: These data are consistent with
      meibomian lipid films having a surfactant layer with a complex bulk layer
      external to this. It is speculated that the bulk layer contains thermotropic
      smectic chiral liquid crystals of CEs that are interacting with the WEs. This
      structure would tend to prevent collapse of the meibomian lipids onto the ocular
      surface and be very tolerant of lipophilic contaminants.

PMID- 22997288
TI  - Retinal nerve fiber layer imaging with spectral-domain optical coherence
      tomography: interpreting the RNFL maps in healthy myopic eyes.
AB  - PURPOSE: To investigate the association between the distribution profile of the
      retinal nerve fiber layer (RNFL) bundles and myopia and its impact on
      interpretation of the RNFL map imaged by a spectral-domain optical coherence
      tomography (SD-OCT). METHODS: the RNFL of 189 myopic eyes from 103 normal healthy
      myopic participants was imaged by an SD-OCT. The angle between the long axes of
      the superotemporal and inferotemporal RNFL bundles determined in the RNFL
      thickness map (the RNFL distribution angle) and the abnormal area in the RNFL
      thickness deviation map were measured. The associations between the RNFL
      distribution angle and the axial length/spherical error, and between the area of
      abnormal RNFL measurement and each of the following: axial length, spherical
      error, RNFL distribution angle, average RNFL thickness, optic disc area, and
      signal strength were analyzed with linear mixed models. RESULTS: The RNFL
      distribution angle decreased with the axial length (P < 0.011). In the univariate
      analysis, the area of abnormal RNFL measurement was positively associated with
      the axial length (P = 0.001); and negatively associated with the RNFL
      distribution angle (P < 0.001), average RNFL thickness (P < 0.001), optic disc
      area (P <= 0.001), and signal strength (P = 0.026). In the multivariate analysis,
      the area of abnormal RNFL measurement was negatively associated with the RNFL
      distribution angle independent of other covariates. CONCLUSIONS: The
      superotemporal and inferotemporal RNFL bundles converged temporally with
      increasing myopia, which was associated with an increase in area of abnormal RNFL
      measurement. The interpretation of the RNFL thickness map in myopic eyes requires
      careful consideration of the distribution pattern of the RNFL bundles.

PMID- 22997290
TI  - An approach to measure blood flow in single choroidal vessel using Doppler
      optical coherence tomography.
AB  - PURPOSE: To evaluate the absolute blood flow rate in a single choroidal vessel
      using Doppler optical coherence tomography (OCT). METHODS: Three choroidal
      vessels were selected in the right eye of three normal subjects, and were
      measured with Doppler OCT at a 1020-nm probe wavelength. The pulsatile change of
      the blood flow was obtained from synchronized measurement of Doppler OCT and
      plethysmography. Absolute blood flow rates in choroidal vessels were calculated
      from Doppler OCT volume data. RESULTS: The cyclic change of the blood flow was
      quantitatively obtained. Absolute blood flow velocities and blood flow rates at
      peak systole [mean (SD)] were 46.9 (12.5) mm/s and 5.9 (3.6) MUL/min,
      respectively. The coefficient of variation of three sets of measurements [mean
      (SD)] was 9.3 (4.9%). CONCLUSIONS: Doppler OCT and plethysmography provided an
      accurate quantitative assessment of the blood flow in choroidal vessels. This
      measurement technique could prove valuable to the study of choroidal blood flow
      in normal and pathologic conditions.

PMID- 22997291
TI  - Prevention and cost control.

PMID- 22997289
TI  - Endogenous production of extracellular adenosine by trabecular meshwork cells:
      potential role in outflow regulation.
AB  - PURPOSE: To investigate the mechanisms for endogenous production of extracellular
      adenosine in trabecular meshwork (TM) cells and evaluate its physiological
      relevance to the regulation of aqueous humor outflow facility. METHODS: Extra
      cellular levels of adenosine monophosphate (AMP) and adenosine in porcine
      trabecular meshwork (PTM) cells treated with adenosine triphosphate (ATP), AMP,
      cAMP or forskolin with or without specific inhibitors of phosphodiesterases
      (IBMX) and CD73 (AMPCP) were determined by high-pressure liquid chromatography
      fluorometry. Extracellular adenosine was also evaluated in cell cultures
      subjected to cyclic mechanical stress (CMS) (20% stretching; 1 Hz) and after
      disruption of lipid rafts with methyl-beta-cyclodextrin. Expression of CD39 and
      CD73 in porcine TM cells and tissue were examined by Q-PCR and Western blot. The
      effect of inhibition of CD73 on outflow facility was evaluated in perfused living
      mouse eyes. RESULTS: PTM cells generated extracellular adenosine from
      extracellular ATP and AMP but not from extracellular cAMP. Increased
      intracellular cAMP mediated by forskolin led to a significant increase in
      extracellular adenosine production that was not prevented by IBMX. Inhibition of
      CD73 resulted, in all cases, in a significant decrease in extracellular
      adenosine. CMS induced a significant activation of extracellular adenosine
      production. Inhibition of CD73 activity with AMPCP in living mouse eyes resulted
      in a significant decrease in outflow facility. CONCLUSIONS: These results support
      the concept that the extracellular adenosine pathway might play an important role
      in the homeostatic regulation of outflow resistance in the TM, and suggest a
      novel mechanism by which pathologic alteration of the TM, such as increased
      tissue rigidity, could lead to abnormal elevation of IOP in glaucoma.

PMID- 22997296
TI  - Infectious diseases. New XMRV studies bring closure--and fresh dispute.

PMID- 22997297
TI  - Astronomy. Warped light reveals infant galaxy on the brink of the 'cosmic dawn'.

PMID- 22997298
TI  - Archaeology. Did Neandertals truly bury their dead?

PMID- 22997299
TI  - Laser fusion. Ignition facility misses goal, ponders new course.

PMID- 22997300
TI  - Infectious disease. An enterprising time for HIV vaccine research.

PMID- 22997302
TI  - Biometrics. China's sharp focus on biometrics.

PMID- 22997301
TI  - Environmental health. Cancers join list of illnesses linked to 9/11 attacks.

PMID- 22997303
TI  - Infectious disease. Despite setbacks, optimism on drugs for hepatitis C.

PMID- 22997304
TI  - Friends in fungi.

PMID- 22997305
TI  - Political science in peril.

PMID- 22997307
TI  - Comment on "A common pesticide decreases foraging success and survival in honey
      bees".
AB  - Henry et al. (Reports, 20 April, p. 348) used a model to predict that colony
      collapse in honey bees could be precipitated by pesticide-induced intoxication
      that disrupts navigation. Here, we show that collapse disappears when the model
      is recalculated with parameter values appropriate to the season when most
      pesticide-treated flowering crops bloom.

PMID- 22997310
TI  - Global health. Global indicators and targets for noncommunicable diseases.

PMID- 22997311
TI  - Ecology. A measurable planetary boundary for the biosphere.

PMID- 22997312
TI  - Materials science. Nanometer-scale printing.

PMID- 22997313
TI  - Structural biology. Versatility from protein disorder.

PMID- 22997314
TI  - Chemistry. Thermally responsive pulsating nanotubules.

PMID- 22997315
TI  - Cancer. Emerging anatomy of the BAP1 tumor suppressor system.

PMID- 22997316
TI  - Sociology. Moving and the neighborhood glass ceiling.

PMID- 22997317
TI  - Disease prevention. It takes more than an apple a day. Introduction.

PMID- 22997319
TI  - Public health measures in disease prevention.

PMID- 22997318
TI  - Task force's prevention advice proves hard to swallow. Interview by Eliot
      Marshall.

PMID- 22997320
TI  - Will an aspirin a day keep cancer away?

PMID- 22997321
TI  - Wondering how the wonder drug works.

PMID- 22997322
TI  - Tackling America's eating habits, one store at a time.

PMID- 22997323
TI  - Uncertain verdict as vitamin D goes on trial.

PMID- 22997324
TI  - Chronic disease vaccines need shot in the arm.

PMID- 22997325
TI  - Can noncommunicable diseases be prevented? Lessons from studies of populations
      and individuals.
AB  - Noncommunicable diseases (NCDs)--mainly cancers, cardiovascular diseases,
      diabetes, and chronic respiratory diseases--are responsible for about two-thirds
      of deaths worldwide, mostly in low- and middle-income countries. There is an
      urgent need for policies and strategies that prevent NCDs by reducing their major
      risk factors. Effective approaches for large-scale NCD prevention include
      comprehensive tobacco and alcohol control through taxes and regulation of sales
      and advertising; reducing dietary salt, unhealthy fats, and sugars through
      regulation and well-designed public education; increasing the consumption of
      fresh fruits and vegetables, healthy fats, and whole grains by lowering prices
      and improving availability; and implementing a universal, effective, and
      equitable primary-care system that reduces NCD risk factors, including
      cardiometabolic risk factors and infections that are precursors to NCDs, through
      clinical interventions.

PMID- 22997326
TI  - Preventing Alzheimer's disease.
AB  - Despite intensive laboratory and clinical research over three decades, an
      effective treatment to delay the onset and progression of Alzheimer's disease is
      not at hand. Recent clinical trial failures suggest that we must treat the
      disease earlier than in its mild to moderate stages, and major progress in
      validating presymptomatic biomarkers now makes secondary prevention trials
      possible. We will learn more about the natural history of the disease and any
      partial therapeutic responses from detailed analyses of recent trial results.
      This process will likely position the field for success, but only with much
      greater investment in all aspects of Alzheimer research and with careful design
      of future trials.

PMID- 22997327
TI  - Changing human behavior to prevent disease: the importance of targeting automatic
      processes.
AB  - Much of the global burden of disease is associated with behaviors--overeating,
      smoking, excessive alcohol consumption, and physical inactivity--that people
      recognize as health-harming and yet continue to engage in, even when undesired
      consequences emerge. To date, interventions aimed at changing such behaviors have
      largely encouraged people to reflect on their behaviors. These approaches are
      often ineffectual, which is in keeping with the observation that much human
      behavior is automatic, cued by environmental stimuli, resulting in actions that
      are largely unaccompanied by conscious reflection. We propose that interventions
      targeting these automatic bases of behaviors may be more effective. We discuss
      specific interventions and suggest ways to determine whether and how
      interventions that target automatic processes can enhance global efforts to
      prevent disease.

PMID- 22997328
TI  - Fetal and early childhood undernutrition, mortality, and lifelong health.
AB  - Child undernutrition is a major public health challenge, estimated to be
      responsible for 2.2 million annual deaths. Implementation of available
      interventions could prevent one-third of these deaths. Emerging evidence suggests
      that breast-feeding can lead to improvements in intelligence quotient in children
      and lower risks of noncommunicable diseases in mothers and children decades
      later. Nonetheless, breast-feeding and complementary feeding practices differ
      greatly from global recommendations. Although the World Health Organization
      recommends that infants receive solely breast milk for the first 6 months of
      life, only about one-third of infants in low-income countries meet this goal,
      just one-third of children 6 to 24 months old in low-income countries meet the
      minimum criteria for dietary diversity, and only one in five who are breast-fed
      receive a minimum acceptable diet. Although the potential effects of improved
      breast-feeding and complementary feeding appear large, funding for research and
      greater use of existing effective interventions seems low compared with other
      life-saving child health interventions.

PMID- 22997329
TI  - Double burden of noncommunicable and infectious diseases in developing countries.
AB  - On top of the unfinished agenda of infectious diseases in low- and middle-income
      countries, development, industrialization, urbanization, investment, and aging
      are drivers of an epidemic of noncommunicable diseases (NCDs). Malnutrition and
      infection in early life increase the risk of chronic NCDs in later life, and in
      adult life, combinations of major NCDs and infections, such as diabetes and
      tuberculosis, can interact adversely. Because intervention against either health
      problem will affect the other, intervening jointly against noncommunicable and
      infectious diseases, rather than competing for limited funds, is an important
      policy consideration requiring new thinking and approaches.

PMID- 22997330
TI  - Why a macroeconomic perspective is critical to the prevention of noncommunicable
      disease.
AB  - Effective prevention of noncommunicable diseases will require changes in how we
      live, and thereby effect important economic changes across populations, sectors,
      and countries. What we do not know is which populations, sectors, or countries
      will be positively or negatively affected by such changes, nor by how much.
      Without this information we cannot know which policies will produce effects that
      are beneficial both for economies and for health.

PMID- 22997332
TI  - Quantum-enhanced optical-phase tracking.
AB  - Tracking a randomly varying optical phase is a key task in metrology, with
      applications in optical communication. The best precision for optical-phase
      tracking has until now been limited by the quantum vacuum fluctuations of
      coherent light. Here, we surpass this coherent-state limit by using a continuous
      wave beam in a phase-squeezed quantum state. Unlike in previous squeezing
      enhanced metrology, restricted to phases with very small variation, the best
      tracking precision (for a fixed light intensity) is achieved for a finite degree
      of squeezing because of Heisenberg's uncertainty principle. By optimizing the
      squeezing, we track the phase with a mean square error 15 +/- 4% below the
      coherent-state limit.

PMID- 22997331
TI  - Neighborhood effects on the long-term well-being of low-income adults.
AB  - Nearly 9 million Americans live in extreme-poverty neighborhoods, places that
      also tend to be racially segregated and dangerous. Yet, the effects on the well
      being of residents of moving out of such communities into less distressed areas
      remain uncertain. Using data from Moving to Opportunity, a unique randomized
      housing mobility experiment, we found that moving from a high-poverty to lower
      poverty neighborhood leads to long-term (10- to 15-year) improvements in adult
      physical and mental health and subjective well-being, despite not affecting
      economic self-sufficiency. A 1-standard deviation decline in neighborhood poverty
      (13 percentage points) increases subjective well-being by an amount equal to the
      gap in subjective well-being between people whose annual incomes differ by
      $13,000--a large amount given that the average control group income is $20,000.
      Subjective well-being is more strongly affected by changes in neighborhood
      economic disadvantage than racial segregation, which is important because racial
      segregation has been declining since 1970, but income segregation has been
      increasing.

PMID- 22997333
TI  - Subtractive patterning via chemical lift-off lithography.
AB  - Conventional soft-lithography methods involving the transfer of molecular "inks"
      from polymeric stamps to substrates often encounter micrometer-scale resolution
      limits due to diffusion of the transferred molecules during printing. We report a
      "subtractive" stamping process in which silicone rubber stamps, activated by
      oxygen plasma, selectively remove hydroxyl-terminated alkanethiols from self
      assembled monolayers (SAMs) on gold surfaces with high pattern fidelity. The
      covalent interactions formed at the stamp-substrate interface are sufficiently
      strong to remove not only alkanethiol molecules but also gold atoms from the
      substrate. A variety of high-resolution patterned features were fabricated, and
      stamps were cleaned and reused many times without feature deterioration. The
      remaining SAM acted as a resist for etching exposed gold features. Monolayer
      backfilling into the lift-off areas enabled patterned protein capture, and 40
      nanometer chemical patterns were achieved.

PMID- 22997334
TI  - Pulsating tubules from noncovalent macrocycles.
AB  - Despite recent advances in synthetic nanometer-scale tubular assembly, conferral
      of dynamic response characteristics to the tubules remains a challenge. Here, we
      report on supramolecular nanotubules that undergo a reversible contraction
      expansion motion accompanied by an inversion of helical chirality. Bent-shaped
      aromatic amphiphiles self-assemble into hexameric macrocycles in aqueous
      solution, forming chiral tubules by spontaneous one-dimensional stacking with a
      mutual rotation in the same direction. The adjacent aromatic segments within the
      hexameric macrocycles reversibly slide along one another in response to external
      triggers, resulting in pulsating motions of the tubules accompanied by a chiral
      inversion. The aromatic interior of the self-assembled tubules encapsulates
      hydrophobic guests such as carbon-60 (C(60)). Using a thermal trigger, we could
      regulate the C(60)-C(60) interactions through the pulsating motion of the
      tubules.

PMID- 22997335
TI  - A crystalline singlet phosphinonitrene: a nitrogen atom-transfer agent.
AB  - A variety of transition metal-nitrido complexes (metallonitrenes) have been
      isolated and studied in the context of modeling intermediates in biological
      nitrogen fixation by the nitrogenase enzymes and the industrial Haber-Bosch
      hydrogenation of nitrogen gas into ammonia. In contrast, nonmetallic nitrenes
      have so far only been spectroscopically observed at low temperatures, despite
      their intermediacy in a range of organic reactions. Here, we report the synthesis
      of a bis(imidazolidin-2-iminato)phosphinonitrene, which is stable at room
      temperature in solution and can even be isolated in the solid state. The bonding
      between phosphorus and nitrogen is analogous to that observed for
      metallonitrenes. We also show that this nitrido phosphorus derivative can be used
      to transfer a nitrogen atom to organic fragments, a difficult task for transition
      metal-nitrido complexes.

PMID- 22997336
TI  - A fully size-resolved perspective on the crystallization of water clusters.
AB  - The number of water molecules needed to form the smallest ice crystals has proven
      challenging to pinpoint experimentally. This information would help to better
      understand the hydrogen-bonding interactions that account for the macroscopic
      properties of water. Here, we report infrared (IR) spectra of precisely size
      selected (H(2)O)(n) clusters, with n ranging from 85 to 475; sodium doping and
      associated IR excitation-modulated photoionization spectroscopy allowed the study
      of this previously intractable size domain. Spectral features indicating the
      onset of crystallization are first observed for n = 275 +/- 25; for n = 475 +/-
      25, the well-known band of crystalline ice around 3200 cm(-1) dominates the OH
      stretching region. The applied method has the potential to push size-resolved IR
      spectroscopy of neutral clusters more broadly to the 100- to 1000-molecule range,
      in which many solvents start to manifest condensed phase properties.

PMID- 22997337
TI  - Structural basis for microtubule binding and release by dynein.
AB  - Cytoplasmic dynein is a microtubule-based motor required for intracellular
      transport and cell division. Its movement involves coupling cycles of track
      binding and release with cycles of force-generating nucleotide hydrolysis. How
      this is accomplished given the ~25 nanometers separating dynein's track- and
      nucleotide-binding sites is not understood. Here, we present a subnanometer
      resolution structure of dynein's microtubule-binding domain bound to microtubules
      by cryo-electron microscopy that was used to generate a pseudo-atomic model of
      the complex with molecular dynamics. We identified large rearrangements triggered
      by track binding and specific interactions, confirmed by mutagenesis and single
      molecule motility assays, which tune dynein's affinity for microtubules. Our
      results provide a molecular model for how dynein's binding to microtubules is
      communicated to the rest of the motor.

PMID- 22997338
TI  - Specifying and sustaining pigmentation patterns in domestic and wild cats.
AB  - Color markings among felid species display both a remarkable diversity and a
      common underlying periodicity. A similar range of patterns in domestic cats
      suggests a conserved mechanism whose appearance can be altered by selection. We
      identified the gene responsible for tabby pattern variation in domestic cats as
      Transmembrane aminopeptidase Q (Taqpep), which encodes a membrane-bound
      metalloprotease. Analyzing 31 other felid species, we identified Taqpep as the
      cause of the rare king cheetah phenotype, in which spots coalesce into blotches
      and stripes. Histologic, genomic expression, and transgenic mouse studies
      indicate that paracrine expression of Endothelin3 (Edn3) coordinates localized
      color differences. We propose a two-stage model in which Taqpep helps to
      establish a periodic pre-pattern during skin development that is later
      implemented by differential expression of Edn3.

PMID- 22997340
TI  - Disruption of reconsolidation erases a fear memory trace in the human amygdala.
AB  - Memories become labile when recalled. In humans and rodents alike, reactivated
      fear memories can be attenuated by disrupting reconsolidation with extinction
      training. Using functional brain imaging, we found that, after a conditioned fear
      memory was formed, reactivation and reconsolidation left a memory trace in the
      basolateral amygdala that predicted subsequent fear expression and was tightly
      coupled to activity in the fear circuit of the brain. In contrast, reactivation
      followed by disrupted reconsolidation suppressed fear, abolished the memory
      trace, and attenuated fear-circuit connectivity. Thus, as previously demonstrated
      in rodents, fear memory suppression resulting from behavioral disruption of
      reconsolidation is amygdala-dependent also in humans, which supports an
      evolutionarily conserved memory-update mechanism.

PMID- 22997339
TI  - Unicellular cyanobacterium symbiotic with a single-celled eukaryotic alga.
AB  - Symbioses between nitrogen (N)(2)-fixing prokaryotes and photosynthetic
      eukaryotes are important for nitrogen acquisition in N-limited environments.
      Recently, a widely distributed planktonic uncultured nitrogen-fixing
      cyanobacterium (UCYN-A) was found to have unprecedented genome reduction,
      including the lack of oxygen-evolving photosystem II and the tricarboxylic acid
      cycle, which suggested partnership in a symbiosis. We showed that UCYN-A has a
      symbiotic association with a unicellular prymnesiophyte, closely related to
      calcifying taxa present in the fossil record. The partnership is mutualistic,
      because the prymnesiophyte receives fixed N in exchange for transferring fixed
      carbon to UCYN-A. This unusual partnership between a cyanobacterium and a
      unicellular alga is a model for symbiosis and is analogous to plastid and
      organismal evolution, and if calcifying, may have important implications for past
      and present oceanic N(2) fixation.

PMID- 22997341
TI  - The ethics of end-of-life care for patients with ESRD.
AB  - Patients with ESRD have extensive and unique palliative care needs, often for
      years before death. The vast majority of patients, however, dies in acute care
      facilities without accessing palliative care services. High mortality rates along
      with a substantial burden of physical, psychosocial, and spiritual symptoms and
      an increasing prevalence of decisions to withhold and stop dialysis all highlight
      the importance of integrating palliative care into the comprehensive management
      of ESRD patients. The focus of renal care would then extend to controlling
      symptoms, communicating prognosis, establishing goals of care, and determining
      end-of-life care preferences. Regretfully, training in palliative care for
      nephrology trainees is inadequate. This article will provide a conceptual
      framework for renal palliative care and describe opportunities for enhancing
      palliative care for ESRD patients, including improved chronic pain management and
      advance care planning and a new model for delivering high-quality palliative care
      that includes appropriate consultation with specialist palliative care.

PMID- 22997342
TI  - Determinants and short-term reproducibility of relative plasma volume slopes
      during hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Hypervolemia is a major cause of morbidity, in part
      because of the lack of well characterized diagnostic tests. The hypothesis was
      that relative plasma volume (RPV) slopes are influenced by ultrafiltration rate,
      directly associate with improvement in arterial oxygen saturation, and are
      reproducible. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: RPV slopes were
      measured on three consecutive hemodialysis sessions. Various relationships were
      tested using mixed models. Reproducibility was assessed by the intraclass
      correlation coefficient. RESULTS: RPV slopes averaged 1.37 +/- 1.45% per hour.
      The mean RPV slopes were steeper on the first dialysis of the week, which
      correlated with a higher ultrafiltration rate; RPV slope and ultrafiltration rate
      were directly related. Increasing ultrafiltration rate quartiles were associated
      with similar change in RPV in the first 1 hour of dialysis but steeper changes in
      RPV subsequently. A direct relationship emerged between increasing RPV slopes and
      increasing arterial oxygen saturation slopes. The intraclass correlation
      coefficient for the relative plasma volume slope was 0.77. CONCLUSIONS: Although
      ultrafiltration rate is a major determinant of RPV slope, similar ultrafiltration
      rates are associated with varying RPV between individuals. Because RPV is
      associated with little change by ultrafiltration rate during the first 1 hour of
      dialysis, probing dry weight during the earlier part of dialysis may be safer.
      RPV slopes are physiologically meaningful, because they are associated with
      parallel changes in arterial oxygenation saturation slopes. RPV slopes are
      reproducible, and therefore, RPV may serve as a useful marker to judge changes in
      volume status within an individual.

PMID- 22997343
TI  - Association of modality with mortality among Canadian Aboriginals.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have shown that Aboriginals and
      Caucasians experience similar outcome on dialysis in Canada. Using the Canadian
      Organ Replacement Registry, this study examined whether dialysis modality
      (peritoneal or hemodialysis) impacted mortality in Aboriginal patients. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This study identified 31,576 adult
      patients (hemodialysis: Aboriginal=1839, Caucasian=21,430; peritoneal dialysis:
      Aboriginal=554, Caucasian=6769) who initiated dialysis between January of 2000
      and December of 2009. Aboriginal status was identified by self-report. Dialysis
      modality was determined 90 days after dialysis initiation. Multivariate Cox
      proportional hazards and competing risk models were constructed to determine the
      association between race and mortality by dialysis modality. RESULTS: During the
      study period, 939 (51.1%) Aboriginals and 12,798 (53.3%) Caucasians initiating
      hemodialysis died, whereas 166 (30.0%) and 2037 (30.1%), respectively, initiating
      peritoneal dialysis died. Compared with Caucasians, Aboriginals on hemodialysis
      had a comparable risk of mortality (adjusted hazards ratio=1.04, 95% confidence
      interval=0.96-1.11, P=0.37). However, on peritoneal dialysis, Aboriginals
      experienced a higher risk of mortality (adjusted hazards ratio=1.36, 95%
      confidence interval=1.13-1.62, P=0.001) and technique failure (adjusted hazards
      ratio=1.29, 95% confidence interval=1.03-1.60, P=0.03) than Caucasians. The risk
      of technique failure varied by patient age, with younger Aboriginals (<50 years
      old) more likely to develop technique failure than Caucasians (adjusted hazards
      ratio=1.76, 95% confidence interval=1.23-2.52, P=0.002). CONCLUSIONS: Aboriginals
      on peritoneal dialysis experience higher mortality and technique failure relative
      to Caucasians. Reasons for this race disparity in peritoneal dialysis outcomes
      are unclear.

PMID- 22997344
TI  - Outcomes of male patients with Alport syndrome undergoing renal replacement
      therapy.
AB  - BACKGROUND AND OBJECTIVES: Patients with the hereditary disease Alport syndrome
      commonly require renal replacement therapy (RRT) in the second or third decade of
      life. This study compared age at onset of RRT, renal allograft, and patient
      survival in men with Alport syndrome receiving various forms of RRT (peritoneal
      dialysis, hemodialysis, or transplantation) with those of men with other renal
      diseases. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with Alport
      syndrome receiving RRT identified from 14 registries in Europe were matched to
      patients with other renal diseases. A linear spline model was used to detect
      changes in the age at start of RRT over time. Kaplan-Meier method and Cox
      regression analysis were used to examine patient and graft survival. RESULTS: Age
      at start of RRT among patients with Alport syndrome remained stable during the
      1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of
      patients with Alport syndrome requiring dialysis or transplantation did not
      change between 1990 and 2009. However, patients with Alport syndrome had better
      renal graft and patient survival than matched controls. Numbers of living-donor
      transplantations were lower in patients with Alport syndrome than in matched
      controls. CONCLUSIONS: These data suggest that kidney failure in patients with
      Alport syndrome is now being delayed compared with previous decades. These
      patients appear to have superior patient survival while undergoing dialysis and
      superior patient and graft survival after deceased-donor kidney transplantation
      compared with patients receiving RRT because of other causes of kidney failure.

PMID- 22997345
TI  - FGF-23 and the progression of coronary arterial calcification in patients new to
      dialysis.
AB  - BACKGROUND AND OBJECTIVE: Fibroblast growth factor 23 (FGF-23), a regulator of
      phosphorus metabolism, is a risk marker in CKD. FGF-23 has been associated with
      coronary arterial calcification (CAC), but it is not known whether FGF-23
      predicts CAC progression in CKD. The aim of this study was to evaluate the
      association of FGF-23 with CAC progression in advanced CKD. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: FGF-23 levels and CAC were measured by
      electrocardiography-triggered multislice computed tomography in 99 individuals
      initiating dialysis. Patients were enrolled in the study from April 2008 to July
      2010. CAC was calculated using Agatston and calcium volume score. Sixty-seven
      study participants had repeat CAC measures at 1 year. Linear regression was used
      to assess the association of FGF-23 with CAC. RESULTS: The mean age of study
      participants was 50 years; 33% were women, and 64% were black. The median FGF-23
      level was 1238 relative units (RU)/ml (interquartile range, 515-2218 RU/ml).
      According to Agatston score, FGF-23 was not associated with baseline CAC (P=0.14)
      but was significantly associated with CAC progression. There was a 192.3-Agatston
      unit change in CAC score per 1-SD change in FGF-23 (P=0.008) in models adjusting
      for known risk factors for CAC and serum phosphate. This association persisted
      after adjustment for high-sensitivity C-reactive protein, 25-OH vitamin D levels,
      and the use of phosphorus binders. Results were similar when change in calcium
      volume score was used. CONCLUSIONS: In individuals with advanced CKD, serum FGF
      23 is strongly associated with CAC progression. FGF-23 may be a marker of
      cardiovascular risk in CKD.

PMID- 22997347
TI  - Bone ultrasound and physical activity in postmenopausal Spanish women.
AB  - We studied the effects of moderate physical activity on bone mass in healthy
      postmenopausal women as assessed by quantitative bone ultrasound. We enrolled a
      total of 326 postmenopausal women (60.95 +/- 8.51 years old and 13.02 +/- 9.52
      years since menopause) and categorized them by weekly physical activity in their
      leisure time (sedentary, moderate, and active). We administered a questionnaire
      on general health and diet and measured bone density by ultrasound on phalanges
      II-V in the nondominant hand. We found no significant difference in the amplitude
      dependent speed of sound (Ad-SoS; p > .05) between sedentary and active women. We
      concluded that the changes induced by moderate physical activity on bone mass are
      minimal in healthy postmenopausal women.

PMID- 22997346
TI  - Endothelin-1 and endothelin receptor gene variants and their association with
      negative outcomes following aneurysmal subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that affects
      approximately 30,000 people a year in the United States. Delayed cerebral
      ischemia (DCI) and cerebral vasospasm (CV) are common complications after aSAH.
      In addition, aSAH patients have a high risk of poor long-term outcomes.
      Endothelin-1 (ET-1), a potent vasoconstrictor, or its two types of receptors, ET
      receptor A (ETA) and ET receptor B (ETB), may play a role in the pathogenesis of
      DCI and CV. Genetic variations within the ET-1, ETA, or ETB genes may also
      account for variance observed in the outcomes of aSAH patients. The purpose of
      this study was to describe the distribution of the Lys198Asn polymorphism, a
      known functional SNP in the ET-1 gene, and tagging SNPs of the ET-1, ETA, and ETB
      genes in individuals recovering from aSAH. This study also investigated the
      relationships among the ET polymorphisms, DCI, and global functional outcomes
      measured at 3 and 6 months after aSAH. Participants included individuals aged 18
      75 years with a diagnosis of aSAH. There was a trend found between the variant
      allele of an ET-1 SNP (rs6912834) and angiographic vasospasm. There were also
      associations found between two ETB SNPs (rs9574124 and rs3027111) and poor
      outcomes as measured by the Glasgow Outcome scale at 3 months. These findings
      support the role of ET-1 and ETB in recovery following aSAH.

PMID- 22997348
TI  - Hindlimb muscle atrophy occurs from short-term undernutrition in rats.
AB  - The purpose of this study was to examine the effect of short-term (7 days)
      undernutrition on Type I (soleus) and Type II (plantaris, gastrocnemius) muscles
      in rats. Male Sprague-Dawley rats (N = 20) were randomly assigned to one of two
      groups: a control group (n = 10) in which animals were allowed to have water and
      pellets ad libitum and an undernourished group (n = 10) in which animals were
      allowed to have 37% of the total food intake of the control group and water ad
      libitum. Body weight and food intake were measured daily. After 7 days, rats were
      anesthetized and the soleus, plantaris, and gastrocnemius muscles and liver were
      dissected. Body weight, liver weight, muscle weight, Types I and II fiber cross
      sectional area, and myofibrillar protein content were determined. After 7 days of
      undernutrition, the undernourished group showed significant decreases (p < .05)
      compared to the control group in body weight, liver weight, muscle weight of
      soleus, plantaris, and gastrocnemius muscles, and cross-sectional areas of Types
      I and II fiber of the plantaris and gastrocnemius muscles.

PMID- 22997349
TI  - In-home monitoring support for dementia caregivers: a feasibility study.
AB  - Technology provides new opportunities for interventions to improve quality and
      access to health care. This study evaluated a telehealth application to support
      family dementia caregivers providing homecare. We explored feasibility of in-home
      video monitoring and feedback to help caregivers and reduce caregiving burden. A
      caregiver-patient dyad was recruited from a Midwestern University Alzheimer's
      Disease Center. The caregiver triggered video recordings on a laptop computer
      using a remote control that also recorded 5 min prior to pressing "record."
      Recordings were automatically uploaded via the Internet for interdisciplinary
      team review and feedback. Issues related to Internet transfer and storage of
      health information and computer security were addressed. Professionals reported
      the value of video recordings for identifying antecedents and evaluating
      caregiver responses. The caregiver reported improved communication and behavior
      management and ease of use. This study developed protocols, processes, and
      contractual arrangements and established the feasibility and benefits of home
      monitoring as a basis for ongoing research.

PMID- 22997350
TI  - How feasible was a bed-height alert system?
AB  - This qualitative and descriptive study examined the feasibility of a bed-height
      alert system as a fall-prevention strategy. The alpha prototype was developed to
      measure and record bed height, and to remind staff to keep patient beds in the
      lowest position. This pilot project was conducted in a 52-bed adult acute
      surgical inpatient care unit of a Michigan community hospital. Qualitative and
      quantitative information was gathered during semistructured interviews of nursing
      staff (18 RNs and 13 PCAs; January-April 2011). Descriptive content analysis and
      descriptive analyses were performed. The overall response rate was 44.9%. The
      mean values of the feasibility questions are all favorable. Staff's comments also
      support the view that the alert system would promote patient safety and prevent
      falls. In short, this system was found to be somewhat useful, feasible,
      appropriate, and accurate. It has the potential to promote patient safety and
      prevent bed-associated injurious falls in inpatient care settings. 

PMID- 22997351
TI  - Population attributable risk estimates for risk factors associated with
      hypertension in an Indian population.
AB  - BACKGROUND: Little evidence exists regarding the magnitude of contribution of
      risk factors associated with hypertension in India. Determination of potentially
      modifiable risk factors is necessary to focus prevention strategies. DESIGN: Age
      matched case-control study. METHODS: A total of 350 hypertensive cases and 350
      controls of both sexes in the age group 20-65 years. Hypertension was defined
      according to JNC VII criteria. Adjusted odds ratio (OR) and population
      attributable risk percentage (PAR %) for hypertension were calculated. RESULTS:
      In multivariate analysis, tobacco users (either tobacco chewing/smoking or both)
      (adjusted OR 5.1, 95% CI 3.6-7.3), tobacco chewing (adjusted OR 3.2, 95% CI 2.2
      4.6), smoking (adjusted OR 2.9, 95% CI 1.9-4.4), and alcohol consumption
      (adjusted OR 1.5, 95% CI 1.1-2.2) was the strongest determinants of hypertension.
      A dose-response relation was found between the number of cigarettes smoked per
      day (chi2 for trend = 26.07; p < 0.0001) and the amount of alcohol consumption
      per day (chi2 for trend = 24.26; p < 0.0001) and the risk of hypertension. PARs
      were 70.3% (95% CI 63.0-77.5) for tobacco use, 45.3% (95% CI 37.1-53.4) for
      tobacco chewing, 31.5% (95% CI 21.3-40.9) for smoking, and 33.6% (95% CI 22.9
      44.4) for alcohol consumption. CONCLUSION: Our results indicate that incident
      hypertension cases are largely attributable to the habit of tobacco use and
      alcohol consumption. Therefore, changing these selected lifestyle factors needs
      to be prioritized as a major strategy for reducing incidence of hypertension in
      our population.

PMID- 22997352
TI  - Tackling inequalities: are secondary prevention therapies for reducing post
      infarction mortality used without disparities?
AB  - BACKGROUND: Mortality due to coronary heart disease has been declining as a
      result of better clinical patient management, including secondary prevention with
      the aid of effective drugs. The clinical challenge remains how to improve
      adherence to evidence-based cardiac care for all patients who can benefit from
      it. The present study aimed to assess the effectiveness of drug use after acute
      myocardial infarction (AMI) in reducing total medium-term mortality and to
      establish whether there are disparities in prescribing all therapies of
      demonstrated effectiveness. DESIGN: We conducted a retrospective cohort study
      between 2002 and 2009 using a record linkage database, considering 1327 patients
      discharged after AMI. METHODS: Cox's regression models were used for the survival
      analysis with time-dependent variables. Logistic regression analyses were
      performed to investigate the inequalities in the actual use of therapies found
      significantly associated with a lower mortality in the survival analyses.
      RESULTS: Therapies independently associated with a lower all-cause mortality risk
      were antiplatelet drugs, beta-blockers, angiotensin-converting enzyme inhibitors,
      and statins. Gender-related differences in prescriptions were seen for statins
      and antiplatelet drugs; age-related differences emerged for all drugs. Associated
      chronic obstructive pulmonary disease reduced the likelihood of patients taking
      the effective treatments. CONCLUSION: The present study revealed disparities in
      the use of treatments for the secondary prevention of coronary heart disease
      unjustifiable on the strength of clinical evidence.

PMID- 22997353
TI  - Unusual presentation of a rare cancer: histiocytic sarcoma in the brain 16 years
      after treatment for acute lymphoblastic leukemia.
AB  - Histiocytic sarcoma (HS) is a very rare hematopoietic neoplasm that has been
      reported in association with other hematological malignancies. Presentation of HS
      in the central nervous system is even less common. Diagnosis of HS requires the
      presence of histiocytic markers and the systematic exclusion of markers of other
      cell lineages. Primary HS central nervous system tumors are aggressive and
      generally have poor outcomes. There are no standard treatment guidelines due to
      lack of clinical trials and a limited number of case reports. Here we present a
      unique case with two primary histiocytic lesions in the brain, refractory to
      systemic and radiation therapies, that developed after being treated for T-cell
      acute lymphoblastic leukemia 16 years prior.

PMID- 22997354
TI  - Acute retinal necrosis secondary to varicella zoster virus in an immunosuppressed
      post-kidney transplant patient.

PMID- 22997355
TI  - Expression of the renin-angiotensin system in a human placental cell line.
AB  - BACKGROUND: The renin-angiotensin system (RAS) is present in human placental
      tissue and participates in regulation of maternal-fetal blood flow during
      pregnancy. RAS expression in placental tissue is regulated by various hormones
      and is altered in various disease conditions. An in vitro system is needed to
      further investigate regulation of the placental RAS. To this end, we studied RAS
      expression in the human placenta-derived cell line, CRL-7548. METHODS: CRL-7548
      cells were cultured in plastic plates. Total RNA was extracted, reverse
      transcribed, and amplified by polymerase chain reaction (PCR) with specific
      primers. Angiotensin II peptide in the culture media was measured by
      radioimmunoassay. Renin activity was detected by radioimmunoassay measuring
      angiotensin I generated. Angiotensin receptor type I was detected by Western
      blot. RESULTS: Specific mRNA for angiotensin, renin, angiotensin converting
      enzyme, and angiotensin receptor type I was detected by real-time PCR. Renin
      activity was detected in the placental cell lysate, and angiotensin II peptide,
      the final product of the RAS system, was detected in cell culture media by
      radioimmunoassay. Angiotensin receptor type I was identified as a 41 kDa protein
      in cell lysates by Western blot. CONCLUSIONS: These results demonstrate that all
      necessary components of the classic RAS are expressed in the human placental cell
      line CRL-7548. This cell line may prove useful as an in vitro system for studying
      RAS regulation in the placenta.

PMID- 22997356
TI  - Transanal excision with radiation therapy for rectal adenocarcinoma.
AB  - OBJECTIVE: To evaluate the efficacy of transanal excision (TAE) combined with
      radiotherapy for rectal adenocarcinoma, assess the ability of pretreatment
      endoscopic ultrasound (EUS) to predict failures, and determine the prognostic
      value of downstaging and complete pathological response. DESIGN: Retrospective
      outcomes study. SETTING: Radiation oncology clinic. PARTICIPANTS: Thirty-eight
      patients with rectal adenocarcinoma. METHODS: The medical records of patients
      treated with radiotherapy from 1998 to 2008 and followed for a median of 5.9
      years were reviewed. RESULTS: Kaplan-Meier estimates of freedom from selected
      endpoints at 5 years after treatment were: overall survival, 79%; cause-specific
      survival, 91%; local control, 90%; and freedom from distant metastasis, 76%.
      Seven patients (21%) had eventual abdominoperineal resection or lower anterior
      resection, four patients had local recurrence, and three patients had incomplete
      treatment or poor margins. T3 lesions clinically staged by EUS were a predictor
      of local failure (P=0.0110), but not distant metastasis (P=0.35). Patients with
      either a pathological or clinical T3 lesion did not have a significantly greater
      rate of metastasis (P=0.096). Patients who were downstaged did not have a
      significantly different rate of local recurrence or metastasis. Patients who
      experienced a complete pathological response did not have a significantly
      different rate of local control or distant metastasis. CONCLUSION: Patients with
      early-stage rectal lesions who undergo preoperative or postoperative radiation
      and TAE have similar outcomes to those who undergo abdominoperineal resection;
      local recurrence was higher for patients with T3 lesions when both were compared.
      Abdominal surgery should be considered for these patients. TAE is reasonable when
      patients are unwilling or unable to tolerate the morbidity of traditional
      transabdominal surgery.

PMID- 22997357
TI  - Adults with ADHD-without insomnia history have subclinical sleep disturbance but
      not circadian delay: an ADHD phenotype?
AB  - OBJECTIVE: To explore the potential ADHD phenotype of ADHD-without reported
      insomnia in comparison with controls and their tolerance of stimulants in a
      cohort rigorously screened for comorbidities. METHOD: Adults meeting Diagnostic
      and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR)
      criteria for ADHD-without insomnia and matched controls were administered a
      sleep/medication-timing questionnaire and the Pittsburgh Sleep Quality Index.
      RESULTS: Among 105 participants, ADHD participants scored in the mild insomnia
      range and showed reduced sleep quality compared with controls, F(3, 101) = 34.9,
      p < .05, but no delay in bedtime/mid-sleep-time circadian measures. Sleep quality
      was similar between stimulant, nonstimulant, and unmedicated groups, chi(2) 2 =
      0.445, p = .80. However, later timing of stimulant dosing was correlated with
      later sleep times, p < .01. CONCLUSION: We isolated a potential phenotype of ADHD
      without circadian delay in adults who demonstrated insomnia/sleep quality
      disturbance by sleep instrument, but lacked sleep-timing delay. Nevertheless,
      sleep delays were associated temporally with late-dosed stimulants in this group.

PMID- 22997358
TI  - The Prevalence of ADHD and Comorbid Disorders in Iranian Adult Male Prison
      Inmates.
AB  - OBJECTIVE: The aim of the present study was to explore the prevalence of ADHD and
      comorbid disorders in a community sample of adult male prisoners in Iran. METHOD:
      Through stratified sampling method, 908 adult male prison inmates in Gorgan
      Prison were recruited on a voluntary basis. Diagnostic assessments were based on
      the Adult ADHD Self-Report Scale Screener and a clinical interview based on
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria and
      psychiatric interview. Comorbid disorders were assessed with the Beck Anxiety
      Inventory, Beck Depression Inventory-Second Edition, and Millon Clinical
      Multiaxial Inventory-III. RESULTS: ADHD was present in 147 participants (16.2%).
      Eighty-five percent of participants with ADHD reported lifetime substance abuse.
      They had higher rates of mood (40.8%) and anxiety (55.1%) disorders. Antisocial
      and borderline personality disorders were also more prevalent among offenders
      with ADHD. CONCLUSION: ADHD is prevalent in offenders and it is associated with
      comorbid disorders. The results emphasize the necessity of treatment programs for
      offenders with ADHD.

PMID- 22997359
TI  - Scientific misconduct: what have we done lately?

PMID- 22997360
TI  - MRI-guided interventions for the treatment of prostate cancer.
AB  - OBJECTIVE: The purpose of this article is to evaluate MRI-guided therapies and to
      investigate their feasibility for focal therapy in prostate cancer patients.
      Relevant articles were retrieved using the PubMed online search engine.
      CONCLUSION: Currently, MRI-guided laser ablation and MRI-guided focused
      ultrasound are the most promising options for focal treatment of the prostate in
      patients with prostate cancer. Other techniques-that is, cryosurgery, microwave
      ablation, and radiofrequency ablation-are, for several and different reasons,
      less suitable for MRI-guided focal therapy of the prostate.

PMID- 22997361
TI  - Balloon-occluded retrograde transvenous obliteration of gastric varices.
AB  - OBJECTIVE: The purpose of this review is to describe the clinical factors related
      to balloon-occluded retrograde transvenous obliteration, including the
      preparation needed, the technique and challenges, and the outcomes. CONCLUSION:
      Although the procedure can be performed when transjugular intrahepatic
      portosystemic shunt is contraindicated or when endoscopic management fails,
      balloon-occluded retrograde transvenous obliteration is successful as a first
      line or second-line therapy. Gastric variceal rebleeding rates are low and
      serious complications are rare. Randomized controlled trials are required to
      evaluate the superiority of this procedure over other methods of treating gastric
      varices and to determine which sclerosant should be used. In the near future,
      this procedure may play a larger role in emergency care and in the management of
      nongastric varices.

PMID- 22997362
TI  - Evaluation and management of transjugular intrahepatic portosystemic shunts.
AB  - OBJECTIVE: The purpose of this article is to describe the evaluation of
      transjugular intrahepatic portosystemic shunts (TIPS) and the management of
      dysfunctional shunts. CONCLUSION: TIPS can become dysfunctional if stenosis
      develops in the shunt or the hepatic vein above the shunt. Screening allows
      detection of stenoses before portal hypertensive-related complications recur.
      Revision of stenotic shunts can be easily accomplished in most cases. Techniques
      for screening and revision will be discussed.

PMID- 22997363
TI  - Budd-Chiari syndrome.
AB  - OBJECTIVE: Budd-Chiari syndrome (BCS) is an uncommon condition characterized by
      obstruction of the hepatic venous outflow tract. Presentation may vary from a
      completely asymptomatic condition to fulminant liver failure. BCS is an example
      of postsinusoidal portal hypertension. The management can be divided into three
      main categories: medical, surgical, and endovascular. The purpose of this article
      is to present an overall perspective of the problem, diagnosis, and management.
      CONCLUSION: BCS requires accurate, prompt diagnosis and aggressive therapy.
      Treatment will vary depending on the clinical presentation, cause, and anatomic
      location of the problem. Patients with BCS are probably best treated in tertiary
      care centers where liver transplantation is available.

PMID- 22997364
TI  - The transjugular intrahepatic portosystemic shunt: an update.
AB  - OBJECTIVE: The purpose of this article is to review the indications, outcomes,
      complications, patient selection, and technical aspects of creating a
      transjugular intrahepatic portosystemic shunt (TIPS). CONCLUSION: The best
      available evidence supports the use of TIPS in secondary prevention of variceal
      bleeding and in refractory ascites, although TIPS is also commonly used for other
      indications such as Budd-Chiari syndrome, hepatic hydrothorax, and acute variceal
      hemorrhage. The TIPS procedure was revolutionized by the introduction of covered
      stents, which dramatically improved long-term shunt patency.

PMID- 22997365
TI  - Current concepts of shoulder arthroplasty for radiologists: Part 1--Epidemiology,
      history, preoperative imaging, and hemiarthroplasty.
AB  - OBJECTIVE: The purpose of this article is to provide a review of indications for
      shoulder arthroplasty, describe preoperative imaging assessment, present new and
      modified designs of shoulder arthroplasty, illustrate normal and abnormal
      postoperative imaging findings, and review key radiographic measurements.
      CONCLUSION: Knowledge of the physiologic purpose, orthopedic trends, imaging
      findings, and complications is important in assessing shoulder prostheses.

PMID- 22997366
TI  - Current concepts of shoulder arthroplasty for radiologists: Part 2--Anatomic and
      reverse total shoulder replacement and nonprosthetic resurfacing.
AB  - OBJECTIVE: The purpose of this article is to provide a review of the indications
      for shoulder arthroplasty, describe preoperative imaging assessment, present new
      and modified designs of shoulder arthroplasty, illustrate normal and abnormal
      postoperative imaging findings, and review key radiographic measurements.
      CONCLUSION: Knowledge of the physiologic purpose, orthopedic trends, imaging
      findings, and complications is important in assessing shoulder prostheses.

PMID- 22997367
TI  - Can low-dose unenhanced chest CT be used for follow-up of lung nodules?
AB  - OBJECTIVE: The purpose of this study is to establish the difference in lung
      nodule volume between standard-dose contrast-enhanced and low-dose unenhanced CT.
      SUBJECTS AND METHODS: Twenty patients with known pulmonary metastases underwent
      three CT examinations on 1 day: two unenhanced low-dose (120 kVp and 30 mAs) and
      a standard-dose (120-140 kVp and 75-200 mAs) contrast-enhanced chest CT
      examinations. For nodules<1000 mm3, nodule volume was quantified using dedicated
      software from the CT manufacturer. Wilcoxon's signed rank tests were used for
      analysis of nodules<=200 mm3 and >200 mm3 (approximately diameter of 8 mm).
      RESULTS: One hundred one nodules (n=69<=200 mm3) were analyzed in 15 of these
      subjects. Measured volume of nodules<=200 mm3 was systematically lower on both
      low-dose unenhanced CT examinations when compared with standard-dose contrast
      enhanced CT (differences, 13.7% and 15.5%, respectively; p<0.0001), but nodule
      volume was not different between low-dose CT (median difference, 1.0%; p=0.10).
      Nodule volume was not systematically different between the protocols for
      nodules>200 mm3 (p>0.30). CONCLUSION: For lung nodules<=200 mm3 (approximately 8
      mm) the measured volume on low-dose unenhanced CT is significantly lower when
      compared with standard-dose contrast-enhanced CT. This effect is likely due to
      contrast administration rather than other imaging parameters, which should be
      taken into account in the follow-up of lung nodules because growth can remain
      undetected or doubling time underestimated.

PMID- 22997368
TI  - Lung cancer associated with cystic airspaces.
AB  - OBJECTIVE: The objectives of this study were to determine the frequency of lung
      cancers associated with a discrete cystic airspace and to characterize the
      morphologic and pathologic features of the cancer and the cystic airspace.
      MATERIALS AND METHODS: We reviewed all diagnosed cases of lung cancer resulting
      from baseline screening (n=595) and annual screening (n=111) in the International
      Early Lung Cancer Action Program to identify those abutting or in the wall of a
      cystic airspace. We also reviewed the pathologic specimens. RESULTS: A total of
      26 lung cancers were identified abutting or in the wall of a cystic airspace. Of
      these, 13 were identified at baseline (13/595, 2%) and 13 at annual screening
      (13/111, 12%), which was significant (p<0.0001). The median circumferential
      portion of wall involved was less for the annual cancers than for the baseline
      ones, but this difference did not reach significance (90 degrees  vs 240 degrees
      , p=0.07). The diagnosis was adenocarcinoma in all but three cases. Histologic
      analysis showed that the cystic space was a bulla, a fibrous walled cyst without
      a defined lining, or a pleural bleb and that in all but one case, the tumor was
      eccentric relative to the airspace and the wall of the airspace was unevenly
      thickened. CONCLUSION: At annual repeat CT screening, the finding of an isolated
      cystic airspace with increased wall thickness should raise the suspicion of lung
      cancer.

PMID- 22997369
TI  - CT grading of lung disease in lymphangioleiomyomatosis.
AB  - OBJECTIVE: The aim of this study was to determine whether a CT-based method shows
      lung lesions, grades disease severity, and evaluates lung tissue in areas
      adjacent to or remote from cysts in patients with lymphangioleiomyomatosis (LAM),
      a cystic lung disease that may cause respiratory failure and death. MATERIALS AND
      METHODS: Three hundred twenty-six CT examinations of 52 patients with LAM were
      studied. After the lungs had been divided into segments and images had been
      subdivided into texture blocks, a multidimensional feature vector was used to
      differentiate and group each texture block. Cysts were outlined, and texture
      around and away from cysts was analyzed. Sequential CT scans and pulmonary
      function test results were evaluated to assess the trend of change.
      Histopathologic examinations were performed of biopsy specimens from 45 patients.
      RESULTS: Differences in texture features between areas adjacent to and areas
      remote from the cysts were observed. The cyst score and sum entropy in areas
      around the cysts correlated with lung function (p<0.0001). Emphysematouslike
      changes in noncystic areas were identified in lung tissue of 31 of 45 patients.
      CONCLUSION: A computational method that uses texture analysis and feature
      correlation can identify and quantify cystic areas where LAM exists and can
      detect abnormalities in areas near cysts. Pathologic data also show lung damage
      in areas adjacent to cysts. Several texture features correlate with lung
      function. Declines in lung function paralleled changes in texture features. In
      LAM, cystic changes alone may not define the extent of lung destruction.

PMID- 22997370
TI  - Oxygen-enhanced MRI, thin-section MDCT, and perfusion SPECT/CT: comparison of
      clinical implications to patient care for lung volume reduction surgery.
AB  - OBJECTIVE: The purpose of our study was to prospectively and directly compare
      capability of O2-enhanced MRI, MDCT, and perfusion SPECT/CT to clinical outcome
      measurements in candidates for lung volume reduction surgery (LVRS). SUBJECTS AND
      METHODS: Twenty-five consecutive candidates for LVRS (20 men and five women; age
      range, 45-76 years) underwent MDCT, O2-enhanced MRI, and perfusion SPECT/CT
      before and after LVRS. Clinical outcomes for each candidate were evaluated in
      terms of differences between pre- and postoperative percentage forced expiratory
      volume in 1 second (%FEV1), Pao2, and 6-minute walking distance. Quantitatively
      assessed upper/lower lung ratios on O2-enhanced MRI, MDCT, and SPECT/CT were
      calculated from regional relative enhancement ratios, functional lung volumes,
      and radioisotope uptakes between upper and lower lungs. Qualitatively assessed
      upper/lower lung ratios on O2-enhanced MRI, MDCT, and SPECT/CT were estimated
      using visual scoring systems. To evaluate the correlation for individual
      upper/lower lung ratios and clinical outcomes, all upper/lower lung ratios were
      correlated with clinical outcomes. Improvements in mean relative enhancement
      ratio were directly correlated with clinical outcomes to assess the capability of
      O2-enhanced MRI to assess therapeutic effect. RESULTS: All quantitatively (
      0.63<=r<=-0.47, p<0.05) and qualitatively (0.41<=r<=0.57, p<0.05) assessed
      upper/lower lung ratios showed moderate and statistically significant correlation
      with clinical outcomes, and improvement in mean relative enhancement ratio showed
      moderate or good correlation, both statistically significant (-0.44<=r<=0.71,
      p<0.05). CONCLUSION: O2-enhanced MRI shows potential for more accurate evaluation
      of postoperative clinical outcome for LVRS candidates than SPECT/CT and can be
      considered at least as reliable as MDCT.

PMID- 22997371
TI  - The effect of liver iron deposition on hepatic apparent diffusion coefficient
      values in cirrhosis.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of hepatic iron
      deposition on apparent diffusion coefficient (ADC) values measured with single
      shot echo-planar imaging (EPI) diffusion-weighted MRI (DWI) in patients with
      liver cirrhosis and in vitro. MATERIALS AND METHODS: Fifty-two patients with
      liver cirrhosis who underwent breath-hold single-shot EPI DWI at 1.5 T before
      liver transplantation were retrospectively assessed. Estimated signal-to-noise
      ratio (SNRest) and ADC were measured in the right hepatic lobe (for b values of
      50 and 500 s/mm2). SNRest and ADC were compared between patients stratified by
      pathologic iron grade using the Mann-Whitney test. Hepatic ADC values were
      correlated to T2* values using the Spearman correlation test in a subset of
      patients. In addition, a phantom consisting of solutions of varying iron
      concentrations was imaged with single-shot EPI DWI and T2* imaging, and iron
      concentration was correlated with ADC and T2*. RESULTS: In phantoms, there was a
      decrease in ADC and T2* with increasing iron concentration (r=-0.95 and -0.92,
      respectively; p<0.05). Patients with hepatic siderosis had significantly lower
      SNRest and ADC compared with patients without siderosis (p<0.0001). SNRest at
      b=50 s/mm2 and b=500 s/mm2 and ADC had a significant negative correlation with
      pathologic iron grade (r=-0.67 to 0.77, p<0.0001). There was a significant
      correlation between liver T2* and ADC (r=0.83, p<0.0001). CONCLUSION: Hepatic
      siderosis lowers liver ADC and should be taken into account when using ADC for
      diagnosing liver cirrhosis.

PMID- 22997372
TI  - Response evaluation in patients with colorectal liver metastases: RECIST version
      1.1 versus modified CT criteria.
AB  - OBJECTIVE: Our retrospective study compared Response Evaluation Criteria in Solid
      Tumors (RECIST) version 1.1 with modified CT criteria to determine their
      respective utilities as a prognostic indicator. Using both sets of criteria, we
      compared treatment responses of patients with colorectal liver metastases treated
      with bevacizumab-containing chemotherapy with those of patients treated with
      chemotherapy alone. MATERIALS AND METHODS: Fifty-nine patients who received
      bevacizumab-containing chemotherapy (n=30, group 1) or chemotherapy alone (n=29,
      group 2) for the treatment of colorectal carcinoma underwent contrast-enhanced CT
      before treatment and 2 months after treatment. Two radiologists determined
      changes in tumor size and density between the pretreatment and 2-month follow-up
      CT images. RECIST 1.1 assesses responses on the basis of changes in tumor size,
      and the modified CT criteria assesses responses on the basis of changes in tumor
      density and size. Responses were correlated with time to tumor progression by log
      rank test. RESULTS: According to RECIST 1.1, nine of 30 patients (30%) in group 1
      and 12 of 29 patients (41%) in group 2 were good responders. According to the
      modified CT criteria, 23 of 30 patients in group 1 (77%) and 23 of 29 patients in
      group 2 (79%) were good responders. As assessed by the modified CT criteria, good
      responders in both groups had significantly longer time to tumor progression than
      poor responders (p<0.05). As assessed by RECIST 1.1, good responders in group 1
      had significantly longer time to tumor progression than poor responders
      (p=0.0154), but there was no difference in group 2. CONCLUSION: Evaluating
      treatment response with tumor size and density changes on CT was a better
      predictor of time to tumor progression than changes in tumor size alone in both
      groups.

PMID- 22997373
TI  - The impact of CT follow-up interval on stages of hepatocellular carcinomas
      detected during the surveillance of patients with liver cirrhosis.
AB  - OBJECTIVE: The purpose of our study was to assess the relationship between time
      intervals of CT examinations and the stages of hepatocellular carcinomas (HCCs)
      detected during the surveillance of patients with liver cirrhosis. MATERIALS AND
      METHODS: In this study, 73 patients with 93 HCCs (reference standard: surgery,
      n=7 [8 HCCs]; biopsy, n=2 [3 HCCs]; imaging criteria, n=64 [82 HCCs]) who showed
      no evidence of HCC on prior CT examinations were included. Patients were
      stratified into three groups based on the time interval between the two CT
      examinations: groups A (interval<=1 year, n=21), B (interval between 1 and 2
      years, n=25), and C (interval>=2 years, n=27). Tumor stages according to the
      American Joint Committee on Cancer (AJCC), the Barcelona Clinic Liver Cancer
      (BCLC) staging system, and the Milan criteria were evaluated retrospectively by
      two reviewers. The Fisher exact test was used to compare tumor stages. Spearman
      correlation coefficients were used to assess the correlation between the CT
      interval and tumor size. RESULTS: One (4%) HCC in group B and four (15%) HCCs in
      group C were larger than 5 cm in diameter, whereas no tumor was larger than 3 cm
      in diameter in group A. There was no difference in tumor diameter between groups,
      but tumor size was positively correlated with time interval between examinations
      (Spearman correlation coefficient, 0.472; p<0.001). In group A, 19 (90%) patients
      had cancers categorized as T1, and the remaining patients had cancers categorized
      as T2. In group B, one (4%) patient had a cancer that was categorized as T3b
      according to the AJCC classification, in the intermediate stage according to the
      BCLC classification, and above the Milan criteria. In group C, three (11%)
      patients had T3b cancers, and five had cancers in either intermediate or higher
      stage and above the Milan criteria. CONCLUSION: HCC detected on CT performed
      within 1 year of a negative examination was at a curable stage in patients with
      liver cirrhosis.

PMID- 22997374
TI  - Diffusion-weighted MRI in the detection of prostate cancer: meta-analysis.
AB  - OBJECTIVE: The objective of our study was to estimate and compare the performance
      of diffusion-weighted imaging (DWI) with other MRI techniques including T2
      weighted MRI for the detection of prostate cancer. MATERIALS AND METHODS:
      Searches of the PubMed and Scopus electronic databases for the terms "prostate,"
      "cancer," "diffusion-weighted imaging," and "magnetic resonance imaging" using an
      end date of December 2010 were completed. All included studies had
      histopathologic correlation; 2*2 contingency data were constructed for each
      study. A Bayesian receiver operating characteristic (ROC) model was used across
      studies to determine sensitivity, specificity, and area under the full or partial
      ROC curve. RESULTS: Nineteen articles consisting of a total of 5892 lesions were
      analyzed. Based on a 95% credible interval, DWI alone yielded a significantly
      better area under the ROC curve, sensitivity, and specificity (0.85, 0.69, 0.89,
      respectively) than T2-weighted imaging alone (0.75, 0.60, 0.76). Combined DWI and
      T2-weighted imaging (0.73, 0.70, 0.83) showed a similar area under the ROC curve
      but significantly better sensitivity and specificity than T2-weighted imaging
      alone. DWI and combined DWI and T2-weighted imaging yielded similar overall
      sensitivity, but DWI alone showed better overall specificity than combined DWI
      and T2-weighted imaging. At specificities of greater than 80%, combined DWI and
      T2-weighted imaging yielded a partial area under the ROC curve (0.138) similar to
      that of DWI alone (0.129) and was significantly better than the partial area
      under the ROC curve of T2-weighted imaging alone (0.070). DWI alone and combined
      DWI and T2-weighted imaging appear to be superior to dynamic contrast-enhanced
      imaging alone (area under the ROC curve, 0.79; sensitivity, 0.58; specificity,
      0.82). CONCLUSION: DWI appears to improve diagnostic performance and can be a
      useful adjunct to conventional anatomic imaging for identifying tumor foci in
      prostate cancer.

PMID- 22997375
TI  - Prostate cancer: multiparametric MRI for index lesion localization--a multiple
      reader study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the utility of
      multiparametric MRI in localization of the index lesion of prostate cancer.
      MATERIALS AND METHODS: Fifty-one patients who underwent 3-T MRI of the prostate
      with a pelvic phased-array coil that included T2-weighted, diffusion-weighted,
      and dynamic contrast-enhanced sequences before prostatectomy were included. Six
      radiologists assessed all images to identify the lesion most suspicious of being
      the index lesion, which was localized to one of 18 regions. A uropathologist
      using the same 18-region scheme reviewed the prostatectomy slides to localize the
      index lesion. MRI performance was assessed by requiring either an exact match or
      an approximate match (discrepancy of up to one region) between the MRI and
      pathologic findings in terms of assigned region. RESULTS: The pathologist
      identified an index lesion in 49 of 51 patients. In exact-match analysis, the
      average sensitivity was 60.2% (range, 51.0-63.3%), and the average positive
      predictive value (PPV) was 65.3% (range, 61.2-69.4%). In approximate-match
      analysis, the average sensitivity was 75.9% (range, 65.3-69.6%), and the average
      PPV was 82.6% (range, 79.2-91.4%). The sensitivity was higher for index lesions
      with a Gleason score greater than 6 in exact-match (74.8% vs 15.3%, p<0.001) and
      approximate-match (88.7% vs 36.1%, p=<0.001) analyses and for index lesions
      measuring at least 1 cm in approximate-match analysis (80.3% vs 58.3%, p=0.016).
      In exact-match analysis, 30.0%, 44.9%, and 79.1% of abnormalities found with one,
      two, and three MRI parameters represented the index lesion (p<0.001). CONCLUSION:
      The sensitivity and PPV of multiparametric MRI for index lesion localization were
      moderate, although they improved in the setting of more aggressive pathologic
      features and a greater number of abnormal MRI parameters, respectively.

PMID- 22997376
TI  - Masters of radiology panel discussion: hyperefficient radiology--can we maintain
      the pace?

PMID- 22997377
TI  - Reviewing imaging examination results with a radiologist immediately after study
      completion: patient preferences and assessment of feasibility in an academic
      department.
AB  - OBJECTIVE: The purpose of this study was to assess patient preferences about
      receiving radiology results and reviewing the images and findings directly with a
      radiologist after completion of an examination. SUBJECTS AND METHODS: A
      prospective survey of English-speaking outpatients undergoing either nononcologic
      CT of the chest, abdomen, and pelvis or nonobstetric ultrasound examinations was
      completed between December 2010 and June 2011. Responses to survey items such as
      preferences regarding communication of results, knowledge of a radiologist, and
      anxiety level before and after radiologist-patient consultation were recorded.
      The average wait time between the end of the imaging examination and the
      consultation and the duration of consultation were documented. RESULTS: Eighty
      six patients (43 men, 43 women; mean age, 52 years) underwent 37 CT and 49
      ultrasound examinations). Forty-eight patients (56%) identified a radiologist as
      a physician who interprets images. Before imaging, 70 patients (81%) preferred
      hearing results from both the ordering provider and the radiologist. This
      percentage increased to 78 (91%) after consultation (p=0.03). Before
      consultation, 84 of the 86 patients (98%) indicated they would be comfortable
      hearing normal results or abnormal results from the person interpreting the
      examination; the number increased to 85 (99%) after consultation. Eighty-five
      patients (99%) agreed or strongly agreed that reviewing their examination
      findings with a radiologist was helpful. Eighty-four patients (98%) indicated
      they wanted the option of reviewing or always wanted to review future examination
      findings with a radiologist. After consultation, anxiety decreased in 41 patients
      (48%), increased in 13 (15%), and was unchanged in 32 (37%) (p=0.0001). The
      average wait for consultation and the duration of consultation were 9.9 and 10.4
      minutes for CT and 1.2 and 7.1 minutes for ultrasound. CONCLUSION: Patients
      prefer hearing examination results from both their ordering provider and the
      interpreting radiologist. Most patients find radiologist consultation beneficial.
      Patients are comfortable hearing results from the radiologist, with most
      displaying decreased anxiety after consultation.

PMID- 22997378
TI  - How much dose can be saved in three-phase CT urography? A combination of normal
      dose corticomedullary phase with low-dose unenhanced and excretory phases.
AB  - OBJECTIVE: The purpose of this study was to investigate the degree to which the
      total radiation dose for CT urography can be lowered by selective reduction of
      the dose in the unenhanced and excretory phases when images in these phases are
      systematically evaluated alongside normal-dose corticomedullary phase images.
      SUBJECTS AND METHODS: Twenty-seven patients (mean age, 74+/-9 years) underwent
      single-bolus CT urography with acquisition in the unenhanced, corticomedullary,
      and 5-minute excretory phases. The scanning parameters for normal-dose CT
      urography were as follows: 16*0.75 mm, 120 kV, and automatic exposure control
      technique reference tube loads of 100, 120, and 100 effective mAs (mAseff). The
      patients also underwent low-dose unenhanced and excretory phase scanning, in
      which the dose was escalated stepwise from a volume CT dose index (CTDIvol) of
      1.7 to 6.6 mGy (reference 20-40-60-80 mAseff). Images were analyzed for quality
      and diagnostic confidence. If low-dose scans of three patients were inadequate,
      the study continued to the next dose level. When 20 patients were successfully
      included in the unenhanced and excretory phase groups, the study ended. Doses
      were calculated with a CT patient dosimetry calculator. RESULTS: Combined with
      the normal dose for corticomedullary phase scanning, doses of CTDIvol 1.5 mGy for
      the unenhanced phase and CTDIvol 2.7 mGy for the excretory phase were sufficient.
      The effective dose for three-phase CT urography was lowered from 16.2 to 9.4 mSv,
      a decrease of 42%. Diagnostic confidence in low-dose images was equal to that in
      normal-dose images when low-dose unenhanced and excretory phase images were read
      along-side normal-dose corticomedullary phase images. CONCLUSION: With a three
      phase CT urographic protocol, significant dose reductions in the unenhanced and
      excretory phases can be achieved when these phases are combined with a normal
      dose corticomedullary phase.

PMID- 22997379
TI  - Improvements in lumbar spine MRI at 3 T using parallel transmission.
AB  - OBJECTIVE: Parallel transmission MRI at 3 T improves image quality by reducing
      dielectric effects with radiofrequency shimming. The purpose of this study was to
      determine whether parallel transmission MRI improves signal-to-noise ratio (SNR)
      and contrast-to-noise ratio (CNR) in lumbar spine MRI at 3 T. MATERIALS AND
      METHODS: Ten healthy volunteers underwent T1-weighted MRI and nine healthy
      volunteers underwent T2-weighted MRI of the lumbar spine. Sagittal and axial T1-
      and T2-weighted images were acquired using parallel transmission MRI and
      conventional MRI. The percentage improvements in SNR and CNR were calculated, and
      statistical significance was determined using a two-tailed Student t test with p
      < 0.05 for significance. RESULTS: The CNR and SNR showed statistically
      significant improvements at all levels of the lumbar spine except SNR at T11 on
      axial T2-weighted imaging. For sagittal T1-weighted imaging, the average
      improvement with parallel transmission MRI was 53% in CNR and 19% in SNR. For
      axial T1-weighted imaging, the average improvement was 48% in CNR and 23% in SNR.
      For sagittal T2-weighted imaging, the average CNR improvement was 38% and the
      average SNR improvement, 20%. For axial T2-weighted scans, the average percentage
      improvement in CNR was greater than 100% and the average SNR improvement was 18%
      with parallel transmission MRI. CONCLUSION: The parallel transmission sequence
      improves image quality of lumbar spine MRI at 3 T, which is quantitatively
      supported by statistically significant improvements in SNR and CNR.

PMID- 22997380
TI  - Clinical and radiologic predictive factors of septic hip arthritis.
AB  - OBJECTIVE: The purpose of our study was to identify the clinical and radiologic
      factors associated with a positive culture during image-guided hip joint
      aspiration. MATERIALS AND METHODS: We performed a retrospective analysis of 167
      consecutive hip aspirations for septic arthritis at a large tertiary medical
      center. Chart review was performed on the following clinical factors: serum WBC
      count>=11*10(3)/MUL, serum erythrocyte sedimentation rate (ESR)>=20 mm/h, C
      reactive protein (CRP)>=100 mg/L, synovial fluid WBC count, synovial fluid
      polymorphonuclear (PMN) leukocytes>=90%, fever, immunosuppression, antibiotic
      use, diabetes, presence of a prosthesis, and IV drug use (IVDU). Radiologic
      studies were reviewed for the following imaging and technical factors: presence
      of a sinus tract, fluid turbidity, volume of fluid (mL) aspirated, and whether
      the fluid analyzed was primarily aspirated or reaspirated after lavage. Logistic
      regression was used to calculate odds ratio (OR) and 95% CI. RESULTS: Of the 167
      aspirations, 29 (17.4%) had positive cultures; 6 of 29 (20.7%) positive cultures
      occurred in reaspirated lavage fluid. On multivariate analysis using logistic
      regression with stepwise backward elimination, the significant clinical and
      radiologic predictors were elevated WBC (OR, 4.4; 95% CI, 1.1-17.3), high
      percentage of synovial fluid PMN leukocytes (OR, 10.6; 95% CI, 2.9-39.8), IVDU
      (OR, 9.0; 95% CI, 1.3-64.7), and fluid turbidity (OR, 20.5; 95% CI, 6.9-61.4).
      CONCLUSION: Positive hip cultures are associated with elevated serum WBC, IVDU,
      high percentage of synovial fluid PMN leukocytes, and fluid aspirate turbidity.
      Reaspiration of lavage fluid with either nonbacteriostatic saline or contrast
      material can yield positive cultures.

PMID- 22997381
TI  - Diagnostic accuracy of MRI in the measurement of glenoid bone loss.
AB  - OBJECTIVE: The purpose of this study is to assess the accuracy of MRI
      quantification of glenoid bone loss and to compare the diagnostic accuracy of MRI
      to CT in the measurement of glenoid bone loss. MATERIALS AND METHODS: MRI, CT,
      and 3D CT examinations of 18 cadaveric glenoids were obtained after the creation
      of defects along the anterior and anteroinferior glenoid. The defects were
      measured by three readers separately and blindly using the circle method. These
      measurements were compared with measurements made on digital photographic images
      of the cadaveric glenoids. Paired sample Student t tests were used to compare the
      imaging modalities. Concordance correlation coefficients were also calculated to
      measure interobserver agreement. RESULTS: Our data show that MRI could be used to
      accurately measure glenoid bone loss with a small margin of error (mean, 3.44%;
      range, 2.06-5.94%) in estimated percentage loss. MRI accuracy was similar to that
      of both CT and 3D CT for glenoid loss measurements in our study for the readers
      familiar with the circle method, with 1.3% as the maximum expected difference in
      accuracy of the percentage bone loss between the different modalities (95%
      confidence). CONCLUSION: Glenoid bone loss can be accurately measured on MRI
      using the circle method. The MRI quantification of glenoid bone loss compares
      favorably to measurements obtained using 3D CT and CT. The accuracy of the
      measurements correlates with the level of training, and a learning curve is
      expected before mastering this technique.

PMID- 22997382
TI  - Fovea alta on MR images: is it a marker of hip dysplasia in young adults?
AB  - OBJECTIVE: The objective of our study was to investigate the association between
      high fovea capitis (fovea alta) and hip dysplasia in young adults. MATERIALS AND
      METHODS: In a retrospective study, blinded observers reviewed 82 pelvic
      radiographic and hip MRI studies of three groups of patients: those with
      developmental dysplasia of the hip (DDH) (center-edge angle, <=20 degrees ),
      those with borderline DDH (center-edge angle, 21 degrees -25 degrees ), and
      control patients (center-edge angle, >25 degrees ). The center-edge angle and
      coxa valga (femoral neck-shaft angle, >135 degrees ) were assessed on pelvic
      radiographs, and fovea alta was assessed on MR images (delta angle, <=10 degrees
      ). The Mann-Whitney and Fisher exact tests were used to correlate fovea alta with
      DDH and with coxa valga, respectively. Interobserver agreement for center-edge
      and delta angles and the diagnostic performance of fovea alta as a marker of DDH
      were calculated. RESULTS: Thirty-one patients with DDH, 23 with borderline DDH,
      and 28 without DDH were included. Excellent interobserver agreement was found for
      center-edge angle (concordance correlation coefficient, 0.94) and for delta angle
      (concordance correlation coefficient, 0.91). Fovea alta had a significant
      association with DDH (p<0.001) but no association with coxa valga (p>0.57). A
      significant difference (p<0.001) was found between patients with DDH (3.4 degrees
      ) and those without DDH (21.7 degrees ) with respect to mean delta angle
      measurements. Fovea alta had 69.4% sensitivity, 82.1% specificity, 67.2% positive
      predictive value, 81.0% negative predictive value, and 75.6% overall accuracy as
      an indicator of DDH. CONCLUSION: Fovea alta shows promise as a strong MRI marker
      of DDH.

PMID- 22997383
TI  - MRI findings in painful metal-on-metal hip arthroplasty.
AB  - OBJECTIVE: The objective of our study was to compare the frequency of osseous and
      soft-tissue abnormalities in patients presenting with hip pain after resurfacing
      arthroplasty and after total hip arthroplasty (THA), correlate the MRI findings
      with histologic results, and determine which MRI findings are predictive of
      aseptic lymphocytic vasculitis-associated lesions. MATERIALS AND METHODS: The MRI
      examinations of patients with metal-on-metal hip prostheses placed at resurfacing
      arthroplasty (n=31) or THA (n=29) were reviewed for osteolysis, synovitis,
      extracapsular disease, synovial pattern, and mode of decompression into adjacent
      bursae. Regional muscles and tendons were assessed for tendinosis, tear, atrophy,
      and edema. Histologic and operative findings were reviewed in 19 patients (20
      hips) who underwent revision surgery. Chi-square tests were performed to detect
      differences between the resurfacing arthroplasty and THA groups. The Wilcoxon
      rank sum test was performed to detect differences in MRI findings in patients
      with and those without aseptic lymphocytic vasculitis-associated lesions.
      RESULTS: Synovitis was detected in 77.4% of resurfacing arthroplasty hips and
      86.2% of THA hips. Extracapsular disease was present in 6.5% of resurfacing
      arthroplasty hips and 10.3% of THA hips. Osteolysis was detected in 9.7% of
      resurfacing arthroplasty hips and 24.1% of THA hips. There was no difference in
      the incidence of synovitis (p=0.51), osteolysis (p=0.17), or extracapsular
      disease (p=0.67) between the resurfacing arthroplasty and THA groups. Patients
      with aseptic lymphocytic vasculitis-associated lesions had higher volumes of
      synovitis (p=0.04) than patients without aseptic lymphocytic vasculitis
      associated lesions. Extracapsular disease and muscle edema were seen only in
      patients with aseptic lymphocytic vasculitis-associated lesions. CONCLUSION:
      Synovitis is common in patients with metal-on-metal hip prostheses and occurs
      with a similar incidence after resurfacing arthroplasty and after THA; osteolysis
      and extracapsular disease are uncommon. The MRI signs most suggestive of aseptic
      lymphocytic vasculitis-associated lesions are high volumes of synovitis,
      extracapsular disease, and intramuscular edema.

PMID- 22997384
TI  - Labral injuries due to iliopsoas impingement: can they be diagnosed on MR
      arthrography?
AB  - OBJECTIVE: Iliopsoas impingement is a new arthroscopic diagnosis that refers to
      an anterior labral injury caused by the iliopsoas tendon. Currently, there are no
      preoperative criteria to establish the diagnosis of iliopsoas impingement. The
      goal of this study was to determine whether there are imaging criteria that would
      identify iliopsoas impingement on preoperative MR arthrography. MATERIALS AND
      METHODS: This study compared the preoperative MR arthrograms of 23 patients who
      had iliopsoas impingement diagnosed at hip arthroscopy with the arthrograms of 24
      patients who did not have iliopsoas impingement found at hip arthroscopy. All of
      the arthroscopies were performed by a single orthopedic hip surgeon. In all cases
      of impingement, there was an isolated injury to the labrum at the 3-o'clock
      position. All were treated by arthroscopic iliopsoas tenotomy performed at the
      labral level. The MR examinations of the 47 patients were evaluated independently
      by two musculoskeletal radiologists who were blinded to the diagnosis. The
      following characteristics of the iliopsoas tendon at the level of the anterior
      labrum were evaluated: lateral dip, increased signal intensity (SI) between the
      iliopsoas tendon and labrum, irregularity of the deep margin of the iliopsoas
      tendon, edema within the iliopsoas tendon or capsule at the 3-o'clock position,
      presence of a labral tear at the 3-o'clock position, dimensions of the iliopsoas
      tendon, and location of iliopsoas tendon as it passed the labrum. Statistical
      analysis was performed using the Kruskal Wallis test, Fisher exact test, and
      Cohen kappa. Values for p less than 0.05 were considered significant. RESULTS:
      Nineteen women (mean age, 35 years) and four men (mean age, 36 years) had central
      iliopsoas impingement. Sixteen women (mean age, 38 years) and eight men (mean
      age, 35 years) did not have central iliopsoas impingement (p=0.318). For the
      impingement and nonimpingement groups, lateral dip of the iliopsoas tendon was
      seen in 15 of 23 (65%) and 17 of 24 (71%) for reader 1 and 18 of 23 (78%) and 11
      of 24 (46%) for reader 2, respectively (p=0.76 and 0.036, respectively). There
      was no difference between the groups for increased SI between the iliopsoas
      tendon and labrum (p=0.38 and 0.82, respectively), irregular deep margin of the
      iliopsoas tendon (p=0.61 and 0.35, respectively), thickness of the iliopsoas
      tendon (p=0.33), or tendon or capsule edema (p=0.37 and 0.77, respectively).
      Reader 1 found 20 of 23 and reader 2 18 of 23 labral tears at the 3-o'clock
      position in the iliopsoas impingement group, with 13 of 24 and 10 of 24 in the
      non-iliopsoas impingement group respectively (p=0.024 and 0.017, respectively).
      The combined iliopsoas tendon width for both readers was 10.2 mm (range, 8.1-14.3
      mm) in women and 11.9 mm (range, 11.1-13.4 mm) in men in the iliopsoas
      impingement group (p=0.0285), and 11.0 mm (range, 9.0-12.6 mm) for women and 11.8
      mm (range, 8.7-15.1 mm) for men in the non-iliopsoas impingement group (p=0.159).
      The iliopsoas tendon most commonly crossed the labrum at the 3-o'clock position
      in both groups (p=0.83-0.17). CONCLUSION: An acetabular labral tear at the 3
      o'clock position should suggest the diagnosis of iliopsoas impingement.

PMID- 22997385
TI  - Could diffusion-weighted imaging detect injured bile ducts of ischemic-type
      biliary lesions after orthotopic liver transplantation?
AB  - OBJECTIVE: The purpose of this article is to discuss whether diffusion-weighted
      imaging (DWI) shows new findings of injured bile ducts in patients with ischemic
      type biliary lesions (ITBL) after orthotopic liver transplantation. SUBJECTS AND
      METHODS: Thirty-five transplant recipients with ITBL (ITBL group), 20 recipients
      without biliary abnormalities on MRCP (control group), and 20 volunteers who did
      not undergo liver transplantation (healthy group) underwent MRI, MRCP, and DWI
      examinations. RESULTS: Twenty-nine ITBL patients showed hyperintensity of bile
      ducts on DWI (82.9%, 29/35). However, only one case in the control group and no
      cases in the healthy group showed hyperintensity. The difference in the signal
      change of bile ducts on DWI between the ITBL and control groups was significant
      (p<0.001). The high accuracy of MRCP and DWI were 96.4% (53/55) and 87.3 (48/55),
      respectively. In the ITBL group, two early ITBL patients showed "normality" of
      bile ducts on MRCP but hyperintensity of small bile ducts on DWI, except thirty
      three patients showed irregular stenosis and dilatation of bile ducts on MRCP
      (94.3%, 33/35). CONCLUSION: MRCP is a noninvasive first-choice for clinical
      diagnosis of ITBL, mainly relying on morphologic abnormality of bile ducts.
      Hyperintensity of the bile ducts with ITBL patients on DWI might offer a method
      of noninvasively and sensitively detecting injured bile ducts, especially for
      early injuries, and may be helpful in detecting etiologic information of ITBL and
      as an effective supplement to MRCP in ITBL.

PMID- 22997386
TI  - Imaging of pediatric patients with inflammatory bowel disease.
AB  - OBJECTIVE: The goal of this review is to examine the current imaging literature
      and develop basic imaging guidelines for evaluation of children with inflammatory
      bowel disease (IBD). The three following typical clinical scenarios in the
      imaging evaluation of IBD are considered: patient with an initial diagnosis of
      suspected IBD, the goals being to determine disease extent and severity and to
      differentiate Crohn disease from ulcerative colitis; patient with known IBD
      presenting with new acute symptoms (fever, peritonitis, leukocytosis) requiring
      urgent evaluation; and patient with known IBD presenting with nonacute
      symptomatic recurrence (abdominal pain, diarrhea), the goals being to assess the
      efficacy of the current treatment and to evaluate the possible need for
      additional medical or surgical intervention. CONCLUSION: Imaging of pediatric
      patients with IBD must balance considerations of diagnostic accuracy against
      concerns about patient exposure to ionizing radiation and tolerance of the
      imaging technique. The imaging modality chosen depends on the clinical
      presentation and expected pathologic finding.

PMID- 22997387
TI  - Second opinion interpretations by specialty radiologists at a pediatric hospital:
      rate of disagreement and clinical implications.
AB  - OBJECTIVE: The objective of our study was to identify whether a substantive
      difference exists between the imaging interpretations of radiologists at outside
      referring institutions and those of radiologists at a tertiary care children's
      hospital and whether such reinterpretation affects the clinical management of
      pediatric patients. MATERIALS AND METHODS: This retrospective chart review
      examined the diagnostic imaging reports of all pediatric patients referred to a
      tertiary care freestanding children's hospital over a 17-month period (January 1,
      2009-May 31, 2010); 773 examinations met the inclusion criteria. The original and
      second interpretations were compared. A fellowship-trained pediatric radiologist
      and neuroradiologist categorized each case using the content of the two radiology
      reports as agreement versus minor or major disagreement, and the results were
      analyzed for statistical significance. A cohort of cases in which a final
      diagnosis could be confirmed was also analyzed to evaluate the accuracy of both
      interpretations. RESULTS: Disagreements were found in 323 of 773 reports (41.8%):
      168 (21.7%) were major and 155 (20.0%), minor. Neurologic studies were most
      frequently requested for reinterpretation, 427 (55.2%), most commonly in the
      setting of trauma, 286 (67.0%). Among the 427 neuroimaging studies, major and
      minor disagreements occurred in 54 (12.6%) and 91 (21.3%) cases, respectively.
      Major disagreements most frequently observed were about the presence of fracture
      and hemorrhage. Among 305 body imaging cases, major and minor disagreements
      occurred in 99 (32.6%) and 57 (18.7%) cases, respectively. The most common
      setting for nontraumatic body imaging was concern for appendicitis (168/305
      [55.1%]); this indication for imaging was responsible for 40.3% of major
      disagreements in nontraumatic abdominal imaging. Reinterpretation was rarely
      requested for radiographic studies (41/773 [5.3%]), which had major and minor
      disagreement rates of 36.6% and 17.1%, respectively. In the cohort of cases
      analyzed for final diagnosis, the second interpretation was more accurate than
      the original in 90.2% of cases with a p value of less than 0.0001. CONCLUSION:
      Our findings suggest that discrepancy rates for second interpretations in studies
      of pediatric patients transferred to tertiary care pediatric institutions are
      substantial. Although the original and second interpretations in the majority of
      cases were in agreement, major discrepancies were prevalent--12.6% and 32.6% of
      neuroimaging and body studies, respectively--and the second interpretations were
      significantly correlated with the final diagnosis. These results indicate that
      interpretations by subspecialty radiologists at a point-of-care facility provide
      important clinical information about the pediatric patient and should be
      recognized by payers as integral to optimal care.

PMID- 22997388
TI  - Prognostic role of MRI enhancement features in patients with breast cancer: value
      of adjacent vessel sign and increased ipsilateral whole-breast vascularity.
AB  - OBJECTIVE: The purpose of this study was to compare adjacent vessel sign,
      increased ipsilateral whole-breast vascularity, and various MRI features as
      described in the American College of Radiology BI-RADS MRI lexicon with
      histopathologic predictors in patients with unilateral breast cancer. MATERIALS
      AND METHODS: We retrospectively evaluated breast MRI examinations of 249 patients
      with histologically confirmed breast cancer. In addition to the BI-RADS MRI
      lexicon, the adjacent vessel sign and increased ipsilateral whole-breast
      vascularity of the cancer-bearing breast were evaluated by two independent
      observers. MRI features were then correlated with histopathologic prognostic
      factors. RESULTS: The adjacent vessel sign was significantly (p=0.023 to p<0.001)
      associated with tumor size, lymph node metastasis, distant metastasis, nuclear
      grade, and expression of estrogen and progesterone receptors. Increased
      ipsilateral whole-breast vascularity was significantly associated with all
      histopathologic predictors (p=0.017 to p<0.001). In multivariate analysis, the
      significant and independent predictors were a spiculated margin and rim
      enhancement for negative estrogen and progesterone receptors, a kinetic curve
      type for higher histologic grade, and an increased ipsilateral whole-breast
      vascularity for larger tumor size, lymph node metastasis, distant metastasis,
      higher nuclear grade, and higher histologic grade. CONCLUSION: In conjunction
      with the standard BI-RADS MRI lexicon, the adjacent vessel sign and increased
      ipsilateral whole-breast vascularity may serve as additional predictors of a poor
      prognosis.

PMID- 22997389
TI  - Is excisional biopsy required after a breast core biopsy yields lobular
      neoplasia?
AB  - OBJECTIVE: The management of lobular neoplasia (LN) on percutaneous core breast
      biopsies remains controversial. Published upgrade rates after surgical excision
      vary widely. This study aims to determine the frequency of malignancy following
      excision in patients with LN found on core biopsy. SUBJECTS AND METHODS: Our
      study identified patients from December 2005 through December 2010 with LN as the
      highest-risk lesion on core biopsy. Patients with flat epithelial atypia on core
      biopsy were not excluded. Per institutional policy, excision was routinely
      recommended. An upgrade from the core biopsy of LN was defined as excisional
      biopsy pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal
      carcinoma (IDC), or invasive lobular carcinoma (ILC). RESULTS: Between December
      2005 and December 2010, 4472 percutaneous breast biopsies were performed, with 71
      patients (1.5%) having LN as the highest-risk lesion on core biopsy. Sixty-seven
      patients (94%) underwent excision. The upgrade rate on excisional biopsy was 16%
      (11/67 patients), with the type of malignancy on excisional biopsy pathology as
      follows: DCIS, 36% (4/11); IDC, 18% (2/11); and ILC, 45% (5/11). All patients
      with pleomorphic lobular carcinoma in situ on core biopsy who proceeded to
      excision were upgraded to malignancy. After excluding patients with discordant
      results, patients with pleomorphic lobular carcinoma in situ, and patients with
      flat epithelial atypia on core biopsy, the upgrade rate of pure LN on excisional
      biopsy was 9%. CONCLUSION: LN on core biopsy warrants excisional biopsy given the
      upgrade rate to malignancy.

PMID- 22997390
TI  - Solitary intraductal papillomas of the breast: MRI features and differentiation
      from small invasive ductal carcinomas.
AB  - OBJECTIVE: Intraductal papilloma of the breast can resemble invasive ductal
      carcinoma (IDC). The purpose of this study was to characterize MRI features of
      solitary intraductal papillomas and identify features that differentiate
      intraductal papillomas from small IDCs. MATERIALS AND METHODS: Forty-four
      intraductal papillomas and 49 small (diameter<=2.0 cm) IDCs confirmed by
      histopathology were included. Analysis of MR findings included morphology, signal
      intensity preenhancement, time-signal intensity curve (TIC), enhancement degree,
      and evolution of enhancement pattern on dynamic contrast-enhanced MRI (DCE-MRI),
      and diffusion-weighted imaging. The chi-square test and independent-samples
      Student t test were performed. RESULTS: Of 44 intraductal papillomas, 27 (61.4%)
      were round or oval and 17 (38.6%) were irregular in shape, whereas 38 of 49
      (77.6%) IDCs showed irregular or lobular shape (p<0.001). Smooth margins were
      seen in 43.2% (19/44) of the intraductal papillomas and 8.2% (4/49) of the IDCs.
      Most intraductal papillomas and IDCs showed slightly higher signal intensity on
      T2-weighted images. On DCE-MRI, 68.2% (30/44) of intraductal papillomas and 12.2%
      (6/49) of IDCs showed an early homogeneous or heterogeneous to delayed rimlike
      enhancement pattern (p=0.000). The difference in early-phase enhancement rates
      between intraductal papillomas (155.41%+/-19.15%) and IDCs (176.40%+/-35.61%) was
      significant (p=0.001). Differences in TIC and apparent diffusion coefficient
      values between the two groups were not significant. CONCLUSION: A low early-phase
      enhancement rate and evolution of the DCE-MRI enhancement pattern from
      homogeneous or heterogeneous enhancement to rim enhancement is more likely to
      suggest intraductal papilloma than IDC.

PMID- 22997391
TI  - Focal hepatic masses in pediatric patients.

PMID- 22997392
TI  - Quality assurance in interventional radiology.

PMID- 22997393
TI  - Burden of alcohol-related injuries on radiology services at a level I trauma
      center.
AB  - OBJECTIVE: The purpose of our study was to evaluate the burden of alcohol-related
      injuries on a radiology department at a level 1 trauma center. MATERIALS AND
      METHODS: We linked the trauma registry (2005-2009) of Harborview Medical Center
      to billing department data and extracted patient demographic and injury-related
      characteristics and the radiology services provided. Multivariate negative
      binomial analysis was used to evaluate the association between blood alcohol
      concentration (BAC) and CT and MRI utilization rates. RESULTS: A total of 125,776
      CT and 4681 MRI examinations were performed on 27,274 patients during the study
      period. Higher BAC was generally associated with higher utilization rates for all
      types of CT even after adjusting for potential confounding variables. Compared
      with patients with a BAC of 0, the greatest increases in utilization were
      observed in individuals with a BAC of 240 mg/dL or more for head CT (incidence
      rate ratio [IRR], 1.43; 95% CI, 1.32-1.54), cervical spine (IRR, 1.45; 95% CI,
      1.32-1.58), and maxillofacial (IRR, 1.66; 95% CI, 1.42-1.95), with no increase
      observed for MRI. This association was more prominent in less severely injured
      patients with utilization rates for head CT (IRR, 1.83; 95% CI, 1.56-2.13),
      abdomen (IRR, 1.46; 95% CI, 1.32-1.63), and thorax (IRR, 1.57; 95% CI, 1.30-1.89)
      in individuals with a BAC of 240 mg/dL or more compared with those with a BAC of
      0. CONCLUSION: Higher BAC was associated with increased CT utilization for most
      body region-specific CT scans and was more strongly associated in patients with
      less severe injuries. Any guideline that could potentially decrease unnecessary
      imaging for patients with alcohol-involved injuries would represent a cost-saving
      strategy.

PMID- 22997394
TI  - Percutaneous placement and management of the Denver shunt for portal hypertensive
      ascites.
AB  - OBJECTIVE: Many patients with cirrhotic effusions in the peritoneal and pleural
      spaces lead a difficult existence. In addition to their decreased mobility and
      physical discomfort, they spend hours in the hospital or an outpatient facility
      undergoing peritoneal and pleural drainage. Liver transplantation is the ultimate
      solution for those with cirrhotic effusions refractory to medical management;
      however, most are on a long waiting list, forcing them to undergo a year or more
      of percutaneous centesis. Transjugular intrahepatic portosystemic shunts offer
      relief to those with cirrhotic ascites but at the cost of accelerated hepatic
      failure and hepatic encephalopathy. This article will review the development of
      the peritoneovenous and pleurovenous shunt, discuss reasons for its loss of
      favor, and suggest its current role in the armamentarium of the interventional
      radiologist. CONCLUSION: Peritoneovenous and pleurovenous shunt creation is a
      procedure that has the potential to significantly improve the quality of life of
      the patient by controlling the fluid collections, reducing dependence on frequent
      drainage procedures, improving renal function, and reducing protein loss.

PMID- 22997395
TI  - Lung CT: Part 1, Mimickers of lung cancer--spectrum of CT findings with
      pathologic correlation.
AB  - OBJECTIVE: The purpose of this article is to describe CT findings of
      miscellaneous pulmonary conditions that mimic lung cancers, especially primary
      cancers, to improve diagnosis of pulmonary lesions. Brief descriptions of patient
      clinical information and pathologic findings will be included and correlated with
      imaging findings in actual cases. CONCLUSION: A wide variety of pulmonary
      conditions present imaging features that mimic those of primary lung cancers and
      are difficult to differentiate from cancer. Awareness of these conditions with an
      understanding of their pathologic background and careful attention to the
      clinical information will help achieve correct diagnoses.

PMID- 22997396
TI  - Lung CT: Part 2, The interstitial pneumonias--clinical, histologic, and CT
      manifestations.
AB  - OBJECTIVE: The interstitial pneumonias are a group of heterogeneous nonneoplastic
      lung diseases that may be idiopathic or associated with an underlying
      abnormality. Although they share some features in common, they also exhibit
      diverse pulmonary manifestations. Imaging plays an essential role in
      characterizing this group of disorders and can often suggest the diagnosis,
      though the final interpretation requires a coordinated effort involving the
      radiologist, pathologist, and clinician. The purpose of this article is to review
      the imaging features of the interstitial pneumonias according to their histologic
      patterns and to provide a brief overview of their clinical presentations.
      CONCLUSION: This article reviews the interstitial pneumonias according to their
      histologic subtypes, including both idiopathic and secondary forms. On
      completion, the reader should have an improved understanding of the
      classification of the interstitial pneumonias, associated causes, characteristic
      imaging features, histologic descriptions, clinical manifestations, and
      prognoses.

PMID- 22997397
TI  - Adaptive iterative dose reduction using 3D processing for reduced- and low-dose
      pulmonary CT: comparison with standard-dose CT for image noise reduction and
      radiological findings.
AB  - OBJECTIVE: The purpose of this study was to determine the utility of adaptive
      iterative dose reduction using 3D processing (AIDR 3D) for image noise reduction
      and assessment of radiologic findings obtained with reduced- and low-dose chest
      CT in patients with various pulmonary diseases. SUBJECTS AND METHODS: Chest CT
      examinations at three different tube current settings and using 16- and 64-MDCT
      scanners were performed for 37 patients. Standard-dose (150 mAs) data were
      reconstructed as thin-section CT without AIDR 3D, and low-dose (25 mAs) and
      reduced-dose (50 mAs) data were reconstructed as thin-section CT without and with
      AIDR 3D. To compare image quality, image noises at all CT doses were
      quantitatively assessed by region of interest measurements. For comparison of
      radiologic finding assessments, likelihoods of occurrence of emphysema, ground
      glass opacity, reticular opacity, bronchiectasis, honeycomb pattern, and nodules
      were evaluated on a 5-point scale. Then, image noise and agreements of radiologic
      findings between standard-dose CT and others were statistically evaluated.
      RESULTS: The image quality scores of reduced- and low-dose CT without AIDR 3D
      were significantly lower than those of both protocols with AIDR 3D and standard
      dose CT (p<0.05). All intermethod agreements for emphysema, ground-glass opacity,
      bronchiectasis, honeycomb pattern, and nodules, except for those observed on low
      dose CT without AIDR 3D, were almost perfect (kappa>0.81). CONCLUSION: AIDR 3D is
      useful for image noise reduction and assessment of radiologic findings obtained
      with reduced- and low-dose CT for patients with various pulmonary diseases.

PMID- 22997398
TI  - MRI after treatment of locally advanced rectal cancer: how to report tumor
      response--the MERCURY experience.
AB  - OBJECTIVE: The Magnetic Resonance Imaging and Rectal Cancer European Equivalence
      (MERCURY) Study validated the use of MRI for posttreatment staging and its
      correlation with survival outcomes. As a consequence, reassessment of MRI scans
      after preoperative therapy has implications for surgical planning, the timing of
      surgery, sphincter preservation, deferral of surgery for good responders, and
      development of further preoperative treatments for radiologically identified poor
      responders. CONCLUSION: In this article we report a validated systematic approach
      to the interpretation of MR images of patients with rectal cancer after
      chemoradiation.

PMID- 22997399
TI  - An intravoxel incoherent motion diffusion-weighted imaging study of prostate
      cancer.
AB  - OBJECTIVE: The purpose of this study is to investigate whether the intravoxel
      incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters are
      different between prostate cancer, benign prostatic hyperplasia (BPH), and
      healthy peripheral zone (PZ). MATERIALS AND METHODS: Detailed diffusion
      measurements of 26 patients with histologically proven prostate cancer have been
      made in this retrospective study. Trace IVIM DWI was performed using 10 b values
      (0, 10, 20, 30, 50, 80, 100, 200, 400, and 1000 s/mm2). Biexponential fits were
      applied to diffusion decay curves to calculate molecular diffusion coefficient,
      perfusion-related diffusion coefficient, and perfusion fraction on the basis of
      the IVIM model. Decay curves were also fit with monoexponential decay functions,
      and a statistical comparison between mono- and biexponential fits was performed.
      Paired t tests were performed to evaluate the statistical significance of the
      parameters of IVIM DWI and apparent diffusion coefficient (ADC) between prostate
      cancer, BPH, and PZ. RESULTS: The chi-square values of biexponential fits were
      smaller than those from monoexponential fits in all cases. Biexponential
      functions provided statistically improved fits over monoexponential functions in
      81% of cases. The ADC, molecular diffusion coefficient, and perfusion fraction in
      prostate cancer were significantly lower than those found in the PZ; however,
      perfusion fractions in prostate cancer and BPH were not significantly different.
      There were no significant differences in the prostate cancer, BPH, and PZ for the
      perfusion-related diffusion coefficient, which had large SDs. CONCLUSION: IVIM
      DWI parameters are significantly different between prostate cancer and PZ. IVIM
      DWI may offer additional information for tissue characterization in the prostate
      gland.

PMID- 22997400
TI  - Retrospective analysis of postinjection ultrasound imaging after platelet-rich
      plasma or autologous blood: observational review of anatomic distribution of
      injected material.
AB  - OBJECTIVE: Characterization of the distribution and imaging characteristics of
      platelet-rich plasma (PRP) and autologous blood after injection is currently
      limited despite the growing use. We sought to improve understanding of the
      distribution of PRP or autologous blood after it has been injected into a tendon
      to evaluate whether injected materials truly stayed within the local region of
      injection. MATERIALS AND METHODS: Fifty ultrasound-guided PRP or autologous blood
      injections performed for tendinopathy were retrospectively reviewed. Consensus
      review of the imaging data was performed by two radiologists to characterize the
      distribution of the injectate (i.e., within the tendon, along the tendon sheath,
      along the paratenon, or leakage into the adjacent joint or surrounding soft
      tissues). The presence of fluid and microbubbles from the injectate served as an
      indicator of material distribution. RESULTS: Image review verified the injectate
      within the tendon in 100% of cases. In 98% of reviewed cases, injected PRP or
      autologous blood dissected beyond the local injection site (defined as >2 cm from
      the site of injection) and was identified in adjacent soft tissues in 51% of
      cases. Visualization of injectate along a paratenon or tendon sheath (when
      applicable) was seen in 86% and 100% of cases respectively; however,
      intraarticular extension was uncommon (8%). CONCLUSION: Our study showed that
      postinjection imaging may be of value in assessing the anatomic distribution of
      injectate after intratendinous therapy. Furthermore, our initial review found
      that in the majority of cases injected blood products tended to distribute beyond
      the local area of injection.

PMID- 22997401
TI  - MRI study of solitary fibrous tumor in the orbit.
AB  - OBJECTIVE: Solitary fibrous tumor (SFT) is a rare lesion of the orbit. The
      purpose of this study is to determine the MRI features of orbital SFTs. MATERIALS
      AND METHODS: We retrospectively reviewed 15 patients with histopathologically
      proven orbital SFTs. All patients underwent orbital MRI. The location, size,
      shape, margin, and MRI signal of 15 lesions were reviewed. The time-intensity
      curve (TIC) of dynamic contrast-enhanced MRI in 14 patients and diffusion
      weighted imaging in four patients were also analyzed. RESULTS: Ten orbital SFTs
      were located in the extraconal space (seven at the superior aspect and three at
      the lateral aspect), three in the retrobulbar intraconal space, one in the
      superomedial aspect of the intraconal space, and one in the lacrimal sac region.
      All SFTs appeared ovoid in configuration and had well-defined margins. The mean
      maximum diameter was 30.2 mm (range, 15-56 mm). Fourteen SFTs appeared
      homogeneously isointense to gray matter on T1-weighted images. On T2-weighted
      images, the lesions showed heterogeneous isointensity in nine patients and
      hypointensity in five patients. The lesions showed heterogeneous marked
      enhancement on contrast-enhanced MRI. Streaky high-signal-intensity areas on T2
      weighted images with marked enhancement were observed in nine patients. Flow-void
      signal was identified in six patients. The TICs of 14 patients showed a washout
      pattern. The contrast index was 1.61+/-0.42, the time to peak enhancement was
      34.15+/-14.04 seconds, and the washout ratio was 37.32%+/-14.37%. The mean
      apparent diffusion coefficient value of four patients was 1.28+/-0.23*10(-3)
      mm2/s. Another case exhibited multicystic appearance. CONCLUSION: Isointense or
      hypointense signal on T2-weighted images, marked enhancement, and a washout TIC
      pattern are the characteristic MRI features of orbital SFTs.

PMID- 22997402
TI  - Papilloma diagnosed at MRI-guided vacuum-assisted breast biopsy: is surgical
      excision still warranted?
AB  - OBJECTIVE: The objective of our study was to determine the frequency of cancer at
      surgery in breast lesions yielding papilloma at MRI-guided 9-gauge vacuum
      assisted biopsy (VAB) and to determine whether any features are associated with
      cancer upgrade. MATERIALS AND METHODS: For this study, 1487 MRI-guided vacuum
      assisted biopsies performed from January 2004 to March 2011 were reviewed.
      Lesions yielding papilloma were identified and classified as papilloma with or
      without atypia. Surgical findings were reviewed to determine the cancer rate.
      Statistical analysis was performed and 95% CIs were calculated. RESULTS:
      Papilloma was identified in 75 of the 1487 MRI-guided vacuum-assisted biopsies
      (5%). These 75 papillomas occurred in 73 women with a median age of 49 years (age
      range, 27-70 years). Of the 75 papillomas, 25 (33%) had atypia and 50 (67%) did
      not on core needle biopsy. Subsequent surgery of 67 of the 75 papillomas (89%)
      yielded ductal carcinoma in situ (DCIS) in four (6%; 95% CI, 2-15%). Surgery
      yielded DCIS in two of 23 papillomas with atypia (9%; 95% CI, 1-28%) at MRI
      guided VAB and in two of 44 papillomas without atypia (5%; 95% CI, 0.4-16%) at
      MRI-guided VAB; these cancer rates did not differ significantly (p=0.6).
      Postmenopausal status (p=0.04) and histologic size of less than 0.2 cm (p=0.04)
      had a significant association with the cancer upgrade rate. CONCLUSION: Papilloma
      with or without atypia was found in 5% of patients who underwent MRI-guided VAB
      during the study period. Surgery revealed cancer in 6%. DCIS was found at surgery
      in 9% of lesions yielding papilloma with atypia versus 5% of lesions yielding
      papilloma without atypia. For lesions yielding papilloma with or without atypia
      at MRI-guided VAB, surgical excision is warranted.

PMID- 22997403
TI  - Ultrasound-guided optical coherence tomography needle probe for the assessment of
      breast cancer tumor margins.
AB  - OBJECTIVE: The purpose of this study was to evaluate a new imaging technique for
      the assessment of breast cancer tumor margins. The technique entails deployment
      of a high-resolution optical imaging needle under ultrasound guidance. Assessment
      was performed on fresh ex vivo tissue samples. CONCLUSION: Use of the ultrasound
      guided optical needle probe allowed in situ assessment of fresh tissue margins.
      The imaging findings corresponded to the histologic findings.

PMID- 22997404
TI  - When interpreting radiologic studies, is the standard of care the same for board
      certified radiologists, radiology residents, and nonradiology physicians?

PMID- 22997405
TI  - Liability of radiologist for ordering contrast medium.

PMID- 22997406
TI  - Understanding that digital radiology images are data following a specific format.

PMID- 22997407
TI  - Availability of prior imaging studies.

PMID- 22997408
TI  - Local thrombolysis for severe cerebral venous sinus thrombosis.

PMID- 22997409
TI  - Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in
      experimental chronic alcohol-induced steatohepatitis.
AB  - AIMS: Chronic alcohol abuse causes steatohepatitis with insulin resistance, which
      impairs hepatocellular growth, survival and metabolism. However, growing evidence
      supports the concept that progressive alcohol-related liver injury may be
      mediated by concurrent mal-signaling through other networks that promote insulin
      resistance, e.g. pro-inflammatory, pro-ceramide and endoplasmic reticulum (ER)
      stress cascades. METHODS: Using the Long Evans rat model of chronic ethanol
      feeding, we characterized the histopathologic and ultrastructural features of
      steatohepatitis in relation to biochemical and molecular indices of tissue
      injury, inflammation, insulin resistance, dysregulated lipid metabolism and ER
      stress. RESULTS: Chronic steatohepatitis with early chicken-wire fibrosis was
      associated with enlargement of mitochondria and disruption of ER structure by
      electron microscopy, elevated indices of lipid storage, lipid peroxidation and
      DNA damage, increased activation of pro-inflammatory cytokines, impaired
      signaling through the insulin receptor (InR), InR substrate-1, Akt, ribosomal
      protein S6 kinase and proline-rich Akt substrate 40 kDa, glycogen synthase kinase
      3beta activation and constitutive up-regulation of ceramide and ER stress-related
      genes. Liquid chromatography coupled with tandem mass spectrometry demonstrated
      altered ceramide profiles with higher levels of C14 and C18, and reduced C16
      species in ethanol-exposed livers. CONCLUSION: The histopathologic and
      ultrastructural abnormalities in chronic alcohol-related steatohepatitis are
      associated with persistent hepatic insulin resistance and pro-inflammatory
      cytokine activation, dysregulated lipid metabolism with altered ceramide profiles
      and both ER and oxidative stress. Corresponding increases in lipid peroxidation,
      DNA damage and protein carbonylation may have contributed to the chronicity and
      progression of disease. The findings herein suggest that multi-pronged
      therapeutic strategies may be needed for effective treatment of chronic alcoholic
      liver disease in humans.

PMID- 22997411
TI  - Determinants of exposure to 2-butoxyethanol from cleaning tasks: a quasi
      experimental study.
AB  - BACKGROUND: The quantitative assessment of airborne cleaning exposures requires
      numerous measurement methods, which are costly and difficult to apply in the
      workplace. Exposure determinants can be used to predict exposures but have yet to
      be investigated for cleaning activities. We identified determinants of exposure
      to 2-butoxyethanol (2-BE), a known respiratory irritant and suspected human
      carcinogen, commonly found in cleaning products. In addition, we investigated
      whether 2-BE exposures can be predicted from exposure determinants and total
      volatile organic compounds (TVOCs) measured with direct reading methods, which
      are easier to apply in field investigations. METHODS: Exposure determinants were
      studied in a quasi-experimental study design. Cleaning tasks were performed
      similarly as in the workplace, but potential factors that can impact exposures
      were controlled. Simultaneously for each task, we measured concentrations of (1)
      2-BE according to the National Institute for Occupational Health and Safety 1430
      method and (2) TVOC with photoionization detectors (PIDs). Simple and multiple
      linear regression analyses were performed to identify 2-BE exposure determinants
      and to develop exposure prediction models. RESULTS: Significant determinants from
      univariate analyses consisted of product type, tasks performed, room volume, and
      ventilation. The best-fit multivariable model was the one comprised of product
      type, tasks performed, 2-BE product concentration, room volume, and ventilation
      (R(2) = 77%). We found a strong correlation between the 2-BE and the TVOC
      concentrations recorded by the PID instruments. A multivariable model with TVOC
      explained a significant portion of the 2-BE concentrations (R(2) = 72%) when
      product type and room ventilation were included in the model. CONCLUSIONS: Our
      results suggest that quantitative exposure assessment for an epidemiologic
      investigation of cleaning health effects may be feasible even without performing
      integrated sampling and analytic measurements.

PMID- 22997410
TI  - Alcohol exposure during late adolescence increases drinking in adult Wistar rats,
      an effect that is not reduced by finasteride.
AB  - AIMS: We tested whether an exposure to alcohol in late adolescence, an age of
      rapid increase in neuroactive steroid precursors, would increase voluntary
      alcohol consumption in adult rats and whether this effect would be modulated by
      finasteride, an inhibitor of neuroactive steroid synthesis. METHODS: In
      Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for
      1 week during late adolescence [postnatal days (PNDs) 51-58], and then measured
      voluntary alcohol consumption 1 month later in adulthood (PNDs 91-104). In
      Experiment 2, finasteride was administered during the forced alcohol exposure in
      late adolescence and, in Experiment 3, during voluntary alcohol consumption in
      adulthood. Plasma was collected at the end of each finasteride treatment to
      confirm the reduction of plasma neuroactive steroid levels. RESULTS: We found
      that a daily 12-h exposure to alcohol for 7 days in late adolescence
      significantly increased voluntary alcohol consumption (4-fold) a month later
      during adulthood. Finasteride administration in late adolescence increased group
      alcohol intake in late adolescence but did not block the effect of adolescent
      alcohol exposure on increasing alcohol preference in adulthood. There was no
      effect of finasteride treatment in adulthood on alcohol preference. CONCLUSIONS:
      A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to
      induce chronically increased alcohol preference in adulthood, indicating that
      this age may be sensitive to the effects of alcohol.

PMID- 22997412
TI  - Manganese in occupational arc welding fumes--aspects on physiochemical
      properties, with focus on solubility.
AB  - Physicochemical properties, such as particle sizes, composition, and solubility
      of welding fumes are decisive for the bioaccessibility of manganese and thereby
      for the manganese cytotoxic and neurotoxic effects arising from various welding
      fumes. Because of the diverse results within the research on welding fume
      solubility, this article aims to review and discuss recent literature on
      physicochemical properties of gas metal arc welding, shielded metal arc welding,
      and flux-cored arc welding fumes, with focus on solubility properties. This
      article also presents a short introduction to the literature on arc welding
      techniques, health effects from manganese, and occupational exposure to manganese
      among welders.

PMID- 22997413
TI  - The use of Benford's law for evaluation of quality of occupational hygiene data.
AB  - Benford's law is the contra-intuitive empirical observation that the digits 1-9
      are not equally likely to appear as the initial digit in numbers resulting from
      the same phenomenon. Manipulated, unrelated, or created numbers usually do not
      follow Benford's law, and as such this law has been used in the investigation of
      fraudulent data in, for example, accounting and to identify errors in data sets
      due to, for example, data transfer. We describe the use of Benford's law to
      screen occupational hygiene measurement data sets using exposure data from the
      European rubber manufacturing industry as an illustration. Two rubber process
      dust measurement data sets added to the European Union ExAsRub project but
      initially collected by the UK Health and Safety Executive (HSE) and British
      Rubber Manufacturers' Association (BRMA) and one pre- and one post-treatment n
      nitrosamines data set collated in the German MEGA database and also added to the
      ExAsRub database were compared with the expected first-digit (1BL) and second
      digit (2BL) Benford distributions. Evaluation indicated only small deviations
      from the expected 1BL and 2BL distributions for the data sets collated by the UK
      HSE and industry (BRMA), respectively, while for the MEGA data larger deviations
      were observed. To a large extent the latter could be attributed to imputation and
      replacement by a constant of n-nitrosamine measurements below the limit of
      detection, but further evaluation of these data to determine why other deviations
      from 1BL and 2BL expected distributions exist may be beneficial. Benford's law is
      a straightforward and easy-to-implement analytical tool to evaluate the quality
      of occupational hygiene data sets, and as such can be used to detect potential
      problems in large data sets that may be caused by malcontent a priori or a
      posteriori manipulation of data sets and by issues like treatment of observations
      below the limit of detection, rounding and transfer of data.

PMID- 22997414
TI  - Three simple guideposts to successful publishing: a Journal of Holistic Nursing
      perspective.

PMID- 22997416
TI  - Complete Genome Sequence of IME13, a Stenotrophomonas maltophilia bacteriophage
      with large burst size and unique plaque polymorphism.
AB  - Stenotrophomonas maltophilia bacteriophage IME13 is a virulent phage with a large
      burst size, exceeding 3,000, much larger than that of any other stenotrophomonas
      phage reported before. It showed effective lysis of Stenotrophomonas maltophilia.
      Additionally, the phage IME13 developed at least three obviously different sizes
      of plaques when a single plaque was picked out and inoculated on a double-layer
      Luria broth agar plate with its host. Here we announce its complete genome and
      describe major findings from its annotation.

PMID- 22997417
TI  - Complete genome sequence of a novel Newcastle disease virus strain isolated from
      a chicken in West Africa.
AB  - The complete genome sequence of an African Newcastle disease virus (NDV) strain
      isolated from a chicken in Togo in 2009 was determined. The genome is 15,198
      nucleotides (nt) in length and is classified in genotype VII in the class II
      cluster. Compared to common vaccine strains, the African strain contains a
      previously described 6-nt insert in the downstream untranslated region of the N
      gene and a novel 6-nt insert in the HN-L intergenic region. Genome length
      differences are a marker of the natural history of NDV. This is the first
      description of a class II NDV strain with a genome of 15,198 nt and a 6-nt insert
      in the HN-L intergenic region. Sequence divergence relative to vaccine strains
      was substantial, likely contributes to outbreaks, and illustrates the continued
      evolution of new NDV strains in West Africa.

PMID- 22997418
TI  - Complete genome sequence of two variant porcine reproductive and respiratory
      syndrome viruses isolated from vaccinated piglets.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) continues to affect
      the Chinese swine industry. Since 2006, variant PRRSV strains sharing two unique
      discontinuous deletions of 30 amino acids in the nonstructural protein Nsp2 have
      become dominant in Chinese swine herds and have caused huge economic losses to
      the swine industry in China. Here we report the complete genome sequence of two
      novel PRRSV variants isolated from vaccinated piglets with additional amino acid
      deletions in Nsp2.

PMID- 22997419
TI  - Genome sequences of a novel HIV-1 CRF53_01B identified in Malaysia.
AB  - A novel HIV-1 genotype designated CRF53_01B was recently characterized from three
      epidemiologically unrelated persons in Malaysia. Here we announced three recently
      isolated full-length genomes of CRF53_01B, which is likely to be phylogenetically
      linked to CRF33_01B, circulating widely in Southeast Asia. The genome sequences
      may contribute to HIV-1 molecular surveillance and future vaccine development in
      the region.

PMID- 22997420
TI  - Complete genome sequences of two Helicobacter pylori bacteriophages isolated from
      Japanese patients.
AB  - Helicobacter pylori causes peptic ulcers and gastric cancer, which lead to
      significantly higher morbidity in Japan than elsewhere in the world. As
      bacteriophage (phage) and host bacteria coevolve, the study of H. pylori phages
      is important to extend understanding of the evolution and pathogenesis of H.
      pylori. Here we report two complete genome sequences of H. pylori phages KHP30
      and KHP40, which were released spontaneously from the most pathogenic East Asian
      type isolates from Japanese patients.

PMID- 22997421
TI  - Complete genome sequence of an H3N2 canine influenza virus from dogs in Jiangsu,
      China.
AB  - A canine influenza virus (CIV) strain of avian origin designated
      A/Canine/Jiangsu/06/2010 (H3N2) was isolated from dogs exhibiting severe
      respiratory disease in Jiangsu, China. We announce the complete genome sequence
      of this viral strain and report major findings from the genomic analysis. This
      sequence will help us understand the molecular characteristics and evolutionary
      of H3N2 CIV in China.

PMID- 22997422
TI  - Complete genome sequence of the Enterobacter cancerogenus bacteriophage Enc34.
AB  - Enterobacter cancerogenus is widely distributed in nature and is generally
      recovered from environmental or vegetal sources. In some cases, it has also been
      associated with human infections. In this study, the complete genomic sequence of
      virulent E. cancerogenus bacteriophage Enc34 was determined. The Enc34 genome is
      60,364 bp in length and contains 80 open reading frames. To our knowledge, this
      is the first report of a bacteriophage infecting E. cancerogenus.

PMID- 22997423
TI  - Genome sequence of a novel HIV-1 circulating recombinant form 54_01B from
      Malaysia.
AB  - We report here the first novel HIV-1 circulating recombinant form (CRF) 54_01B
      (CRF54_01B) isolated from three epidemiologically unlinked subjects of different
      risk groups in Malaysia. These recently sampled recombinants showed a complex
      genome organization composed of parental subtype B' and CRF01_AE, with identical
      recombination breakpoints observed in the gag, pol, and vif genes. Such a
      discovery highlights the ongoing active generation and spread of intersubtype
      recombinants involving the subtype B' and CRF01_AE lineages and indicates the
      potential of the new CRF in bridging HIV-1 transmission among different risk
      groups in Southeast Asia.

PMID- 22997424
TI  - Complete genome sequence of canine papillomavirus type 10.
AB  - Papillomaviruses are epitheliotropic, nonenveloped, circular, double-stranded DNA
      viruses within the family Papillomaviridae that are associated with benign and
      malignant tumors in humans and animals. We report the complete genome sequence of
      canine papillomavirus type 10 identified from a pigmented plaque located on the
      head of a mixed-breed bloodhound.

PMID- 22997425
TI  - Full genome sequence of a novel coxsackievirus B5 strain isolated from
      neurological hand, foot, and mouth disease patients in China.
AB  - Coxsackievirus B5 (CVB5) belongs to the human enterovirus B species within the
      family Picornaviridae. We report the complete genome sequence of a novel CVB5
      strain, CVB5/SD/09, that is associated with neurological hand, foot, and mouth
      disease in China. The complete genome consists of 7,399 nucleotides, excluding
      the 3' poly(A) tail, and has an open reading frame that maps between nucleotide
      positions 744 and 7301 and encodes a 2,185-amino-acid polyprotein. Phylogenetic
      analysis based on different genome region regions reveals that CVB5/SD/09 belongs
      to a novel CVB5 lineage, and similarity plotting and bootscanning analysis based
      on the whole genome of CVB5 in the present study and those available in GenBank
      indicate that the genome of CVB5/SD/09 has a mosaic-like structure, suggesting
      that recombination between different CVB5 strains may occur.

PMID- 22997426
TI  - Complete genome sequence of Pectobacterium carotovorum subsp. carotovorum
      bacteriophage My1.
AB  - Pectobacterium carotovorum subsp. carotovorum, a member of the Enterobacteriaceae
      family, is an important plant-pathogenic bacterium causing significant economic
      losses worldwide. P. carotovorum subsp. carotovorum bacteriophage My1 was
      isolated from a soil sample. Its genome was completely sequenced and analyzed for
      the development of an effective biological control agent. Sequence and
      morphological analyses revealed that phage My1 is a T5-like bacteriophage and
      belongs to the family Siphoviridae. To date, there is no report of a
      Pectobacterium-targeting siphovirus genome sequence. Here, we announce the
      complete genome sequence of phage My1 and report the results of our analysis.

PMID- 22997427
TI  - Complete genome sequence of a novel pestivirus from sheep.
AB  - We report here the complete genome sequence of pestivirus strain Aydin/04-TR,
      which is the prototype of a group of similar viruses currently present in sheep
      and goats in Turkey. Sequence data from this virus showed that it clusters
      separately from the established and previously proposed tentative pestivirus
      species.

PMID- 22997428
TI  - Identification of new autoantigens by protein array indicates a role for IL4
      neutralization in autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is an unresolving inflammation of the liver of unknown
      cause. Diagnosis requires the exclusion of other conditions and the presence of
      characteristic features such as specific autoantibodies. Presently, these
      autoantibodies have relatively low sensitivity and specificity and are identified
      via immunostaining of cells or tissues; therefore, there is a diagnostic need for
      better and easy-to-assess markers. To identify new AIH-specific autoantigens, we
      developed a protein microarray comprising 1626 human recombinant proteins,
      selected in silico for being secreted or membrane associated. We screened sera
      from AIH patients on this microarray and compared the reactivity with that of
      sera from healthy donors and patients with chronic viral hepatitis C. We
      identified six human proteins that are specifically recognized by AIH sera. Serum
      reactivity to a combination of four of these autoantigens allows identification
      of AIH patients with high sensitivity (82%) and specificity (92%). Of the six
      autoantigens, the interleukin-4 (IL4) receptor fibronectin type III domain of the
      IL4 receptor (CD124), which is expressed on the surface of both lymphocytes and
      hepatocytes, showed the highest individual sensitivity and specificity for AIH.
      Remarkably, patients' sera inhibited STAT6 phosphorylation induced by IL4 binding
      to CD124, demonstrating that these autoantibodies are functional and suggesting
      that IL4 neutralization has a pathogenetic role in AIH.

PMID- 22997429
TI  - Does endurance training protect from lipotoxicity?

PMID- 22997430
TI  - Protective effect of Nrf2 and catalase in maternal diabetes-induced perinatal
      hypertension and kidney disease.

PMID- 22997431
TI  - Cardiac natriuretic peptides: contributors to cardiac cachexia or possible anti
      obesity agents or both?

PMID- 22997433
TI  - Metallothionein-mediated antioxidant defense system and its response to exercise
      training are impaired in human type 2 diabetes. Diabetes 2005;54:3089-3094.

PMID- 22997432
TI  - HLA-B7-restricted islet epitopes are differentially recognized in type 1 diabetic
      children and adults and form weak peptide-HLA complexes.
AB  - The cartography of beta-cell epitopes targeted by CD8(+) T cells in type 1
      diabetic (T1D) patients remains largely confined to the common HLA-A2
      restriction. We aimed to identify beta-cell epitopes restricted by the HLA-B7
      (B*07:02) molecule, which is associated with mild T1D protection. Using DNA
      immunization on HLA-B7-transgenic mice and prediction algorithms, we identified
      GAD and preproinsulin candidate epitopes. Interferon-gamma (IFN-gamma) enzyme
      linked immunospot assays on peripheral blood mononuclear cells showed that most
      candidates were recognized by new-onset T1D patients, but not by type 2 diabetic
      and healthy subjects. Some epitopes were highly immunodominant and specific to
      either T1D children (GAD(530-538); 44% T cell-positive patients) or adults
      (GAD(311-320); 38%). All epitopes displayed weak binding affinity and stability
      for HLA-B7 compared with HLA-A2-restricted ones, a general feature of HLA-B7.
      Single-cell PCR analysis on beta-cell-specific (HLA-B7 tetramer-positive) T cells
      revealed uniform IFN-gamma and transforming growth factor-beta (TGF-beta) mRNA
      expression, different from HLA-A2-restricted T cells. We conclude that HLA-B7
      restricted islet epitopes display weak HLA-binding profiles, are different in T1D
      children and adults, and are recognized by IFN-gamma(+)TGF-beta(+)CD8(+) T cells.
      These features may explain the T1D-protective effect of HLA-B7. The novel
      epitopes identified should find valuable applications for immune staging of HLA
      B7(+) individuals.

PMID- 22997436
TI  - Comment on: Schuit et al. beta-Cell-specific gene repression: a mechanism to
      protect against inappropriate or maladjusted insulin secretion? Diabetes
      2012;61:969-975.

PMID- 22997441
TI  - Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 22997442
TI  - Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines
      for diagnosis, treatment and follow-up.

PMID- 22997443
TI  - Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 22997444
TI  - Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 22997445
TI  - Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines
      for diagnosis, treatment and follow-up.

PMID- 22997446
TI  - Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 22997447
TI  - Management of cancer pain: ESMO Clinical Practice Guidelines.

PMID- 22997448
TI  - Cardiovascular toxicity induced by chemotherapy, targeted agents and
      radiotherapy: ESMO Clinical Practice Guidelines.
AB  - Cardiovascular (CV) toxicity is a potential short- or long-term complication of
      various anticancer therapies. Some drugs, such as anthracyclines or other
      biological agents, have been implicated in causing potentially irreversible
      clinically important cardiac dysfunction. Although targeted therapies are
      considered less toxic and better tolerated by patients compared with classic
      chemotherapy agents, rare but serious complications have been described, and
      longer follow-up is needed to determine the exact profile and outcomes of related
      cardiac side-effects. Some of these side-effects are irreversible, leading to
      progressive CV disease, and some others induce reversible dysfunction with no
      long-term cardiac damage to the patient. Assessment of the prevalence, type and
      severity of cardiac toxicity caused by various cancer treatments is a
      breakthrough topic for patient management. Guidelines for preventing, monitoring
      and treating cardiac side-effects are a major medical need. Efforts are needed to
      promote strategies for cardiac risk prevention, detection and management,
      avoiding unintended consequences that can impede development, regulatory approval
      and patient access to novel therapy. These new ESMO Clinical Practice Guidelines
      are the result of a multidisciplinary cardio-oncology review of current evidence
      with the ultimate goal of providing strict criteria-based recommendations on CV
      risk prevention, assessment, monitoring and management during anticancer
      treatment.

PMID- 22997449
TI  - Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines.

PMID- 22997450
TI  - Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 22997451
TI  - Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 22997452
TI  - Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 22997453
TI  - Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 22997454
TI  - Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 22997455
TI  - Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines
      for diagnosis, treatment and follow-up.

PMID- 22997456
TI  - Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 22997457
TI  - ESMO Consensus Conferences: another source of ESMO Clinical Practice Guidelines.

PMID- 22997458
TI  - Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 22997459
TI  - Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 22997460
TI  - Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 22997461
TI  - Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 22997462
TI  - Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 22997463
TI  - A dual promoter region with overlapping activator sequences drives the expression
      of gas vesicle protein genes in haloarchaea.
AB  - Gas vesicle formation in haloarchaea involves 14 gas vesicle protein (gvp) genes.
      The strong promoter P(A) drives the expression of gvpACNO, which encodes the
      major gas vesicle structural proteins GvpA and GvpC, whereas the oppositely
      oriented promoter P(D) initiates the synthesis of the two regulator proteins,
      GvpD and GvpE. GvpE activates P(A) and P(D), and requires a 20 nt upstream
      activator sequence (UAS). UAS(A) and UAS(D) partially overlap in the centre of
      the 35 bp intergenic region. The basal and GvpE-induced activities of P(A) and
      P(D) were investigated in Haloferax volcanii transformants. Each UAS consists of
      two 8 nt portions (P(A), 1A+2A; P(D), 1D+2D), and mutations in the overlapping 1A
      and 1D portions affected the GvpE induction of both promoters. Substitution of
      one of the UAS portions by a nonsense sequence showed that a complete UAS is
      required for activation. The activation of P(A) was more efficient compared with
      P(D). Promoter P(A) with UAS(A) in configuration 1A+1A was still activated by
      GvpE, but P(D) was not inducible with UAS(D) in configuration 1D+1D. The TATA box
      and/or transcription factor B recognition element (BRE) were exchanged between
      P(A) and P(D). All elements of P(A) functioned well in the environment of 'P(D)'
      and transferred the stronger P(A) activity to 'P(D)'. In contrast, the respective
      'P(A)' chimeras were less active, and BRE(D) was not functional in the
      environment of 'P(A)'. The relative strengths of the two promoters were
      substantially determined by the BRE. A 4 nt scanning mutagenesis uncovered an
      additional regulatory element in the region between TATA(D) and the
      transcriptional start site of gvpD.

PMID- 22997464
TI  - Slr0643, an S2P homologue, is essential for acid acclimation in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - Every cyanobacterial species contains genes encoding site-2-protease (S2P)
      homologues. The studied prokaryotic S2P homologues play essential roles in
      regulating stress responses through intramembrane proteolysis of membrane-bound
      anti-sigma factors. Here, the gene encoding Slr0643, one of four S2P homologues
      in Synechocystis sp. PCC 6803, was insertionally disrupted to explore its
      physiological role. Only a partially segregated mutant was obtained, indicating
      the essentiality of the gene product for growth. A pivotal role of fully
      functional Slr0643 in acid acclimation was demonstrated by defective acid
      acclimation to pH 6.5 in the mutant and transient induction of slr0643 in the
      wild-type after transfer from pH 7.5 to 6.5. DNA microarray and quantitative RT
      PCR analyses of mutant and wild-type strains at pH 7.5 versus pH 6.5 identified
      genes involved in early acid acclimation and revealed genes expressed
      differentially due to slr0643 disruption. Early acid acclimation to pH 6.5 in the
      wild-type strain included upregulation of sigH, hik16 and hik35 and
      downregulation of pcrR and sigG, as well as downregulation of porins and
      upregulation of inorganic carbon and nitrogen transporters. The inability of the
      mutant strain to survive at pH 6.5 was found to be related to defective
      photosynthesis and excess expression of NADH dehydrogenase, together with
      excessive upregulation of carbon transporter and repression of nitrogen
      transporter and metabolism genes. Most interestingly, analysis of microarray data
      revealed the close relationship between slr0643 disruption and expression of the
      sigH operon. Thus it is suggested that Slr0643/Sll0857/SigH might act through an
      S2P/anti-Sigma factor/Sigma factor mechanism to play a role in acid acclimation.

PMID- 22997465
TI  - What is your research question? An introduction to the PICOT format for
      clinicians.

PMID- 22997466
TI  - The JCCA is delighted to announce the recent appointment of Dr. Kent Stuber DC,
      MSc to Associate Editor.

PMID- 22997467
TI  - Acute sciatica and progressive neurological deficit secondary to facet synovial
      cysts: A report of two cases.
AB  - OBJECTIVE: To describe two patients with lumbar facet synovial cysts causing
      sciatica and progressive neurological deficit. CLINICAL FEATURES: A 52-year-old
      female with bilateral sciatica and a neurological deficit that progressed to a
      foot drop; and a 54-year-old female with worsening sciatica and progressive calf
      weakness were seen at a major tertiary care centre. Diagnostic imaging studies
      revealed the presence of spinal nerve root impingement by large facet synovial
      cysts. INTERVENTIONS AND OUTCOMES: Activity modification, gabapentinoid and non
      steroidal anti-inflammatory medications were unsuccessful in ameliorating either
      patient's symptoms. One patient had been receiving ongoing lumbar chiropractic
      spinal manipulative therapy despite the onset of a progressive neurological
      deficit. Both patients eventually required surgery to remove the cyst and
      decompress the affected spinal nerve roots. CONCLUSION: Patients with acute
      sciatica who develop a progressive neurological deficit while under care, require
      prompt referral for axial imaging and surgical consultation. Primary care spine
      clinicians need to be aware of lumbar facet synovial cysts as a possible cause of
      acute sciatica and the associated increased risk of the patient developing a
      progressive neurological deficit.

PMID- 22997468
TI  - Fascia: a morphological description and classification system based on a
      literature review.
AB  - Fascia is virtually inseparable from all structures in the body and acts to
      create continuity amongst tissues to enhance function and support. In the past
      fascia has been difficult to study leading to ambiguities in nomenclature, which
      have only recently been addressed. Through review of the available literature,
      advances in fascia research were compiled, and issues related to terminology,
      descriptions, and clinical relevance of fascia were addressed. Our multimodal
      search strategy was conducted in Medline and PubMed databases, with other
      targeted searches in Google Scholar and by hand, utilizing reference lists and
      conference proceedings.IN AN EFFORT TO ORGANIZE NOMENCLATURE FOR FASCIAL
      STRUCTURES PROVIDED BY THE FEDERATIVE INTERNATIONAL COMMITTEE ON ANATOMICAL
      TERMINOLOGY (FICAT), WE DEVELOPED A FUNCTIONAL CLASSIFICATION SYSTEM WHICH
      INCLUDES FOUR CATEGORIES OF FASCIA: i) linking, ii) fascicular, iii) compression,
      and iv) separating fasciae. Each category was developed from descriptions in the
      literature on gross anatomy, histology, and biomechanics; the category names
      reflect the function of the fascia.An up-to-date definition of fascia is
      provided, as well as descriptions of its function and clinical features. Our
      classification demonstrates the use of internationally accepted terminology in an
      ontology which can improve understanding of major terms in each category of
      fascia.

PMID- 22997469
TI  - Two cases of work-related lateral epicondylopathy treated with Graston
      Technique(r) and conservative rehabilitation.
AB  - OBJECTIVE: To chronicle the conservative treatment and management of two work
      related cases of lateral elbow pain diagnosed as lateral epicondylopathy.
      CLINICAL FEATURES: PATIENT 1: A 48-year old female presented with gradual onset
      of right lateral elbow pain over the course of six weeks related to work
      activities of repetitive flexion/extension movements of the wrist and finger
      keying.  PATIENT 2: A 47-year old female presented with gradual onset of left
      lateral elbow pain over the course of four weeks related to work activities of
      repetitive squeezing and gripping. INTERVENTION AND OUTCOME: The conservative
      treatment approach consisted of activity modification, bracing, medical
      acupuncture with electrical stimulation, Graston Technique(r), and rehabilitative
      exercise prescription. Outcome measures included verbal pain rating scale (VPRS),
      QuickDASH Work Module Score (QDWMS), and a return to regular work activities.
      Both patients attained resolution of their complaints, and at eight month follow
      up reported no recurrence of symptoms. CONCLUSION: A combination of conservative
      rehabilitation strategies may be used by chiropractors to treat work-related
      lateral epicondylopathy and allow for individuals to minimize lost time related
      to this condition.

PMID- 22997470
TI  - Rehabilitation and treatment of a recreational golfer with hip osteoarthritis: a
      case report.
AB  - OBJECTIVE: This case study reviews the conservative chiropractic treatment of hip
      osteoarthritis (OA) and the prescription of a rehabilitation program for a
      recreational golfer. CLINICAL FEATURES: A 49-year-old registered nurse/ college
      instructor presented with a five year history of left hip OA and pain, recent
      right hip pain and occasional low back stiffness. Once her symptoms improved, a
      golf-specific functional rehabilitation program was prescribed in preparation for
      the upcoming golf season. INTERVENTION AND OUTCOME: The initial treatment
      included ultrasound, soft tissue and myofascial therapy, mobilizations,
      acupuncture and home advice. Rehabilitative exercises included core and scapular
      stability exercises, general conditioning, golf specific stretches, functional
      swinging, proprioceptive and strengthening exercises, and referral to a swing
      coach. The positive outcomes included increased ranges of motion, decreased pain,
      as well as improvements in golf driving distance and endurance. SUMMARY:
      Conservative management and golf-specific rehabilitation prescription appears to
      be beneficial for hip OA and recreational golf performance in this case.

PMID- 22997471
TI  - Spinal infection: a case report.
AB  - OBJECTIVE: To present a case of a patient with spinal infection (SI) and
      highlight the chiropractor's role in the prevention or minimization of
      devastating complications of SI. BACKGROUND: Recent literature trends suggest an
      increasing prevalence of SI. Patients with SI most commonly present with
      unremitting progressive back pain and may or may not have fever or neurological
      signs. To avoid negative post-infection sequelae, establishing an early diagnosis
      and treatment is crucial. CLINICAL FEATURES: A 29-year-old female diagnosed with
      L5-S1 disc herniation with impingement of the right S1 nerve root opted for
      surgical management. Iatrogenic bowel perforation during her spinal surgery
      resulted in contamination of the spinal surgical site, and findings in keeping
      with disco-osteomyelitis with epidural and paraspinal phlegmon formation were
      visualized on contrast enhanced MRI. CONCLUSION: Recent trends of increased
      spinal infection urge a heightened awareness by the chiropractor. The
      chiropractor can provide early diagnosis and supportive multidisciplinary care
      for such patients.

PMID- 22997472
TI  - Conservative management of Achilles Tendinopathy: a case report.
AB  - OBJECTIVE: To chronicle the conservative treatment and management of a 77-year
      old female patient presenting with chronic pain of 8 months duration in the
      midportion of the achilles tendon diagnosed as achilles tendinopathy. CLINICAL
      FEATURES: The main clinical feature was pain in the midportion of the achilles
      tendon, 2 to 6 cm proximal to the calcaneal insertion. Symptom onset was gradual
      and unrelated to any acute trauma or overt injury mechanism. INTERVENTION AND
      OUTCOME: The conservative treatment approach consisted of medical acupuncture
      with electrical stimulation, Graston Technique(r), eccentric calf training, and
      rehabilitative exercise prescription. Outcome measures included verbal pain
      rating scale, lower extremity functional scale (LEFS), and a return to activities
      of daily living (ADLs). The patient attained long-term resolution of her
      complaint and at 12 month follow-up reported no recurrence of symptoms.
      CONCLUSION: A combination of conservative rehabilitation strategies may be used
      by chiropractors to treat midportion achilles tendinopathy and allow an
      individual to return to pain free ADLs in a timely manner.

PMID- 22997473
TI  - Conservative management of a 31 year old male with left sided low back and leg
      pain: a case report.
AB  - OBJECTIVE: This case study reported the conservative management of a patient
      presenting with left sided low back and leg pain diagnosed as a left sided L5-S1
      disc prolapse/herniation. CLINICAL FEATURES: A 31-year-old male recreational
      worker presented with left sided low back and leg pain for the previous 3-4
      months that was exacerbated by prolonged sitting. INTERVENTION AND OUTCOME: The
      plan of management included interferential current, soft tissue trigger point and
      myofascial therapy, lateral recumbent manual low velocity, low amplitude traction
      mobilizations and pelvic blocking as necessary. Home care included heat, icing,
      neural mobilizations, repeated extension exercises, stretching, core muscle
      strengthening, as well as the avoidance of prolonged sitting and using a low back
      support in his work chair. The patient responded well after the first visit and
      his leg and back pain were almost completely resolved by the third visit.
      SUMMARY: Conservative chiropractic care appears to reduce pain and improve
      mobility in this case of a L5-S1 disc herniation. Active rehabilitative treatment
      strategies are recommended before surgical referral.

PMID- 22997474
TI  - Confocal microscopy on the beamline: novel three-dimensional imaging and sample
      positioning.
AB  - Confocal microscopy, a technique that has been extensively applied in cellular
      biological studies, may also be applied to the visualization and three
      dimensional imaging of protein crystals at high resolution on synchrotron
      beamlines. Protein crystal samples are examined using a commercially available
      confocal microscope adapted for cryogenic use. A preliminary test using a custom
      confocal design adapted for beamline use is also presented. The confocal optics
      configuration is compatible with nonlinear imaging techniques such as two-photon
      excited fluorescence imaging and second harmonic generation. The possibilities of
      this method are explored using two modes: fluorescence and reflection confocal.
      In fluorescence mode, small amounts of dye are introduced into the crystal
      through soaking or growth conditions. Under such conditions, protein crystals are
      easily resolved from salts and amorphous precipitates, which do not generally
      take up dye. Reflection mode, which does not require dye, still exhibits greater
      resolution and sensitivity to surface detail than conventional wide-field
      microscopy as a result of the confocal optics configuration. The inherent three
      dimensional nature of the method means that on-axis sample views (along the
      direction of the X-ray beam) can be reconstructed from an off-axis configuration,
      simplifying the beamline setup and providing uniquely detailed views of
      cryogenically cooled crystals.

PMID- 22997475
TI  - Enhancing the volume and the optical quality of hen egg-white lysozyme crystals
      by coupling the salt concentration gradient crystallization method with a
      magnetic field.
AB  - The effect of coupling the salt concentration gradient crystallization method
      with the use of the paramagnetic salt MnCl(2) and a magnetic field is reported.
      The use of a simple magnetic device is proposed to have a significant effect on
      hen egg-white lysozyme crystal growth. Large single crystals greater than 10
      mm(3) in volume with optical perfection were consistently obtained in this study.

PMID- 22997476
TI  - The influence of surfactant on the propagation of a semi-infinite bubble through
      a liquid-filled compliant channel.
AB  - We investigate the influence of a soluble surfactant on the steady-state motion
      of a finger of air through a compliant channel. This study provides a basic model
      from which to understand the fluid-structure interactions and physicochemical
      hydrodynamics of pulmonary airway reopening. Airway closure occurs in lung
      diseases such as respiratory distress syndrome and acute respiratory distress
      syndrome as a result of fluid accumulation and surfactant insufficiency. This
      results in 'compliant collapse' with the airway walls buckled and held in
      apposition by a liquid occlusion that blocks the passage of air. Airway reopening
      is essential to the recovery of adequate ventilation, but has been associated
      with ventilator-induced lung injury because of the exposure of airway epithelial
      cells to large interfacial flow-induced pressure gradients. Surfactant
      replacement is helpful in modulating this deleterious mechanical stimulus, but is
      limited in its effectiveness owing to slow surfactant adsorption. We investigate
      the effect of surfactant on micro-scale models of reopening by computationally
      modelling the steady two-dimensional motion of a semi-infinite bubble propagating
      through a liquid-filled compliant channel doped with soluble surfactant. Many
      dimensionless parameters affect reopening, but we primarily investigate how the
      reopening pressure p(b) depends upon the capillary number Ca (the ratio of
      viscous to surface tension forces), the adsorption depth parameter lambda (a bulk
      concentration parameter) and the bulk Peclet number Pe(b) (the ratio of bulk
      convection to diffusion). These studies demonstrate a dependence of p(b) on
      lambda, and suggest that a critical bulk concentration must be exceeded to
      operate as a low-surface-tension system. Normal and tangential stress gradients
      remain largely unaffected by physicochemical interactions - for this reason,
      further biological studies are suggested that will clarify the role of wall
      flexibility and surfactant on the protection of the lung from atelectrauma.

PMID- 22997477
TI  - Introduction to the Special Issue on Job Satisfaction in Fisheries in the Global
      South.

PMID- 22997478
TI  - Job Satisfaction in the Shrimp Trawl Fisheries of Chennai, India.
AB  - Shrimp trawling represents an important fishing metier in South India, generating
      high levels of employment and economic value. It is also a contested metier,
      ostensibly contributing to environmental degradation and social inequality. This
      paper investigates the job satisfaction of crew members (captains and workers) on
      board the shrimp trawlers of Chennai (former Madras). Research took place in 2007
      and 2008 (N = 137). Results suggest a general satisfaction with being in the
      fishery. However, a little over three-fifths of fishers said they would be
      willing to change fishing metier and about one-half said they would leave the
      occupation. About one-half also said they would not advise a young person to
      enter the occupation. The tendency to move away from the fishery is argued to
      reflect a growing pessimism about the future of the shrimp trawl fisheries, but
      also an increasing awareness of other economic opportunities.

PMID- 22997479
TI  - Which Fishers are Satisfied in the Caribbean? A Comparative Analysis of Job
      Satisfaction Among Caribbean Lobster Fishers.
AB  - Lobster fishing (targeting the spiny lobster Panulirus argus) is an important
      economic activity throughout the Wider Caribbean Region both as a source of
      income and employment for the local population as well as foreign exchange for
      national governments. Due to the high unit prices of the product, international
      lobster trade provides a way to improve the livelihoods of fisheries-dependent
      populations. The specie harvested is identical throughout the region and end
      market prices are roughly similar. In this paper we wish to investigate to which
      extent lobster fishers' job satisfaction differs in three countries in the
      Caribbean and how these differences can be explained by looking at the national
      governance arrangements.

PMID- 22997480
TI  - Job Satisfaction in Fisheries Compared.
AB  - This article draws comparative lessons from seven job satisfaction studies on
      marine capture fishing that were recently carried out in nine countries and three
      geographical regions-Asia, Africa, and the Caribbean. The seven studies made use
      of an identical job satisfaction assessment tool and present information on a
      selection of metiers mainly in the small-scale and semi-industrial fishing
      sectors. The responses manifest statistically significant geographical variation.
      Multidimensional plots and cluster analyses lead the authors to identify three
      clusters: (1) Southeast Asian (Vietnam and Thailand); (2) Caribbean (Belize,
      Nicaragua, Dominican Republic) and (3) Afro-Indian (Senegal, Guinea Bissau, and
      India). Jamaica is a significant outlier. On a general level, the authors
      conclude that fishers who report that they are not interested in leaving the
      occupation of fishing score higher on three traditional job satisfaction scales
      basic needs, social needs and self actualization. Those who say they would leave
      fishing for another occupation are younger, have less fishing experience and
      smaller households. The latter findings are of relevance with regard to the
      pressing need, felt by fisheries managers, to move fishers out of the fishery.

PMID- 22997481
TI  - Modified control grid interpolation for the volumetric reconstruction of fluid
      flows.
AB  - Complex applications in fluid dynamics research often require more highly
      resolved velocity data than direct measurements or simulations provide. The
      advent of stereo PIV and PCMR techniques has advanced the state-of-the-art in
      flow velocity measurement, but 3D spatial resolution remains limited. Here a new
      technique is proposed for velocity data interpolation to address this problem.
      The new method performs with higher quality than competing solutions from the
      literature in terms of accurately interpolating velocities, maintaining fluid
      structure and domain boundaries, and preserving coherent structures.

PMID- 22997482
TI  - Influence of graphical weights' interpretation and filtration algorithms on
      generalization ability of neural networks applied to digit recognition.
AB  - In this paper, the method of the graphical interpretation of the single-layer
      network weights is introduced. It is shown that the network parameters can be
      converted to the image and their particular elements are the pixels. For this
      purpose, weight-to-pixel conversion formula is used. Moreover, new weights'
      modification method is proposed. The weight coefficients are computed on the
      basis of pixel values for which image filtration algorithms are implemented. The
      approach is applied to the weights of three types of the models: single-layer
      network, two-layer backpropagation network and the hybrid network. The
      performance of the models is then compared on two independent data sets. By means
      of the experiments, it is presented that the adjustment of the weights to new
      values decreases test error value compared to the error obtained for initial set
      of weights.

PMID- 22997483
TI  - CRP and TNF-alpha  induce PAPP-A expression in human peripheral blood mononuclear
      cells.
AB  - OBJECTIVE: The effects of C-reactive protein (CRP) and tumor necrosis factor
      alpha (TNF-alpha) on pregnancy-associated plasma protein-A (PAPP-A) expression in
      human peripheral blood mononuclear cells (PBMCs) require further investigation.
      METHODS: The PAPP-A levels in culture supernatants, PAPP-A mRNA expression, and
      cellular PAPP-A expression were measured in human PBMCs isolated from fresh blood
      donations provided by 6 healthy volunteers (4 donations per volunteer). Analyses
      were conducted by ultrasensitive ELISA, western blotting, and RT-PCR following
      stimulation with CRP or TNF-alpha cytokines. RESULTS: PAPP-A mRNA and protein
      levels after CRP stimulation peaked at 24 hours, whereas peak PAPP-A mRNA and
      protein levels were achieved after TNF-alpha stimulation at only 2 and 8 hours,
      respectively. These findings indicate the dose-dependent effect of CRP and TNF
      alpha stimulation. Actinomycin D treatment completely prevented CRP and TNF-alpha
      induction of PAPP-A mRNA and protein expression. Additionally, nuclear factor-
      (NF-) kappaB inhibitor (BAY11-7082) potently inhibited both CRP and TNF-alpha
      stimulated PAPP-A mRNA and protein expression. CONCLUSIONS: Human PBMCs are
      capable of expressing PAPP-A in vitro, expression that may be regulated by CRP
      and TNF-alpha through the NF-kappaB pathway. This mechanism may play a
      significant role in the observed increase of serum PAPP-A levels in acute
      coronary syndrome (ACS).

PMID- 22997484
TI  - Most Used Codons per Amino Acid and per Genome in the Code of Man Compared to
      Other Organisms According to the Rotating Circular Genetic Code.
AB  - My previous theoretical research shows that the rotating circular genetic code is
      a viable tool to make easier to distinguish the rules of variation applied to the
      amino acid exchange; it presents a precise and positional bio-mathematical
      balance of codons, according to the amino acids they codify. Here, I demonstrate
      that when using the conventional or classic circular genetic code, a clearer
      pattern for the human codon usage per amino acid and per genome emerges. The most
      used human codons per amino acid were the ones ending with the three hydrogen
      bond nucleotides: C for 12 amino acids and G for the remaining 8, plus one codon
      for arginine ending in A that was used approximately with the same frequency than
      the one ending in G for this same amino acid (plus *). The most used codons in
      man fall almost all the time at the rightmost position, clockwise, ending either
      in C or in G within the circular genetic code. The human codon usage per genome
      is compared to other organisms such as fruit flies (Drosophila melanogaster),
      squid (Loligo pealei), and many others. The biosemiotic codon usage of each
      genomic population or 'Theme' is equated to a 'molecular language'. The C/U
      choice or difference, and the G/A difference in the third nucleotide of the most
      used codons per amino acid are illustrated by comparing the most used codons per
      genome in humans and squids. The human distribution in the third position of most
      used codons is a 12-8-2, C-G-A, nucleotide ending signature, while the squid
      distribution in the third position of most used codons was an odd, or uneven,
      distribution in the third position of its most used codons: 13-6-3, U-A-G, as its
      nucleotide ending signature. These findings may help to design computational
      tools to compare human genomes, to determine the exchangeability between
      compatible codons and amino acids, and for the early detection of incompatible
      changes leading to hereditary diseases.

PMID- 22997485
TI  - When less is more: Line-drawings lead to greater boundary extension than color
      photographs.
AB  - Is boundary extension (false memory beyond the edges of the view; Intraub &
      Richardson, 1989) determined solely by the schematic structure of the view or
      does the quality of the pictorial information impact this error? To examine this
      color photograph or line-drawing versions of 12 multi-object scenes (Experiment
      1: N=64) and 16 single-object scenes (Experiment 2: N=64) were presented for 14-s
      each. At test, the same pictures were each rated as being the "same", "closer-up"
      or "farther away" (5-pt scale). Although the layout, the scope of the view, the
      distance of the main objects to the edges, the background space and the gist of
      the scenes were held constant, line-drawings yielded greater boundary extension
      than did their photographic counterparts for multi-object (Experiment 1) and
      single-object (Experiment 2) scenes. Results are discussed in the context of the
      multisource model and its implications for the study of scene perception and
      memory.

PMID- 22997486
TI  - Epigenetic regulation of B lymphocyte differentiation, transdifferentiation, and
      reprogramming.
AB  - B cell development is a multistep process that is tightly regulated at the
      transcriptional level. In recent years, investigators have shed light on the
      transcription factor networks involved in all the differentiation steps
      comprising B lymphopoiesis. The interplay between transcription factors and the
      epigenetic machinery involved in establishing the correct genomic landscape
      characteristic of each cellular state is beginning to be dissected. The
      participation of "epigenetic regulator-transcription factor" complexes is also
      crucial for directing cells during reprogramming into pluripotency or lineage
      conversion. In this context, greater knowledge of epigenetic regulation during B
      cell development, transdifferentiation, and reprogramming will enable us to
      understand better how epigenetics can control cell lineage commitment and
      identity. Herein, we review the current knowledge about the epigenetic events
      that contribute to B cell development and reprogramming.

PMID- 22997487
TI  - Alcohol Use and HIV Risk among Juvenile Drug Court Offenders.
AB  - Juvenile drug courts (JDC) largely focus on marijuana and other drug use
      interventions. Yet, JDC offenders engage in other high-risk behaviors, such as
      alcohol use and sexual risk behaviors, which can compromise their health, safety
      and drug court success. An examination of alcohol use and sexual risk behaviors
      among 52 male substance abusing young offenders found that over 50% were using
      alcohol, 37% reported current marijuana use and one-third of all sexual
      intercourse episodes were unprotected. After accounting for recent marijuana use,
      the odds of a juvenile having vaginal or anal sex was 6 times greater if they had
      recently used alcohol. Juvenile drug courts may benefit from delivering alcohol
      and sexual risk reduction interventions to fully address the needs of these young
      offenders.

PMID- 22997488
TI  - Thermoelectric properties of Ca(1-x)Gd(x)MnO(3-delta) (0.00, 0.02, and 0.05)
      systems.
AB  - Polycrystalline samples of Ca(1-x)Gd(x)MnO(3-delta) (x = 0.00, 0.02, and 0.05)
      have been studied by X-ray diffraction (XRD), electrical resistivity (rho),
      thermoelectric power (S), and thermal conductivity (kappa). All the samples were
      single phase with an orthorhombic structure. The Seebeck coefficient of all the
      samples was negative, indicating that the predominant carriers are electrons over
      the entire temperature range. The iodometric titration measurements indicate that
      the electrical resistivity of Ca(1-x)Gd(x)MnO(3-delta) correlated well with the
      average valence of Mn(v+) and oxygen deficiency. Among the doped samples,
      Ca0.98Gd0.02MnO(3-delta) had the highest dimensionless figure of merit 0.018 at
      300 K, representing an improvement of about 125% with respect to the undoped
      GaMnO(3-delta) sample at the same temperature.

PMID- 22997489
TI  - Arachidonic acid derivatives and their role in peripheral nerve degeneration and
      regeneration.
AB  - After peripheral nerve injury, a process of axonal degradation, debris clearance,
      and subsequent regeneration is initiated by complex local signaling, called
      Wallerian degeneration (WD). This process is in part mediated by neuroglia as
      well as infiltrating inflammatory cells and regulated by inflammatory mediators
      such as cytokines, chemokines, and the activation of transcription factors also
      related to the inflammatory response. Part of this neuroimmune signaling is
      mediated by the innate immune system, including arachidonic acid (AA) derivatives
      such as prostaglandins and leukotrienes. The enzymes responsible for their
      production, cyclooxygenases and lipooxygenases, also participate in nerve
      degeneration and regeneration. The interactions between signals for nerve
      regeneration and neuroinflammation go all the way down to the molecular level. In
      this paper, we discuss the role that AA derivatives might play during WD and
      nerve regeneration, and the therapeutic possibilities that arise.

PMID- 22997490
TI  - Gender differences and the trend in the acute myocardial infarction: a 10-year
      nationwide population-based analysis.
AB  - It is not clear whether gender is associated with different hospitalization cost
      and lengths for acute myocardial infarction (AMI). We identified patients
      hospitalized for primary diagnosis of AMI with (STEMI) or without (NSTEMI) ST
      elevation from 1999 to 2008 through a national database containing 1,000,000
      subjects. As compared to that in 1999~2000, total (0.350/00  versus 0.060/00, P <
      0.001) and male (0.590/00  versus 0.070/00, P < 0.001) STEMI hospitalization
      percentages were decreased in 2007~2008, but female STEMI hospitalization
      percentages were not different from 1999 to 2008. However, NSTEMI hospitalization
      percentages were similar over the 10-year period. The hospitalization age for
      AMI, STEMI, and NSTEMI was increased over the 10-year period by 14, 9, and 7
      years in male, and by 18, 18, and 21 years in female. The female and male
      hospitalization cost and lengths were similar in the period. As compared to
      nonmedical center, the hospitalization cost for STEMI in medical center was
      higher in male patients, but not in female patients, and the hospitalization cost
      for NSTEMI was higher in both male and female gender. We found significant
      differences between male and female, medical center and non-medical center, or
      STEMI and NSTEMI on medical care over the 10-year period.

PMID- 22997491
TI  - Decrease in the antioxidant capacity in beverages containing tea extracts during
      storage.
AB  - The aim of this work was to determine antioxidant capacity of beverages
      containing black, white, and green tea extracts using the photochemiluminescence
      method, and to monitor its changes based on the storage temperature and time.
      Samples were stored at two different temperatures (refrigerated at 4 degrees C
      and laboratory temperature 22 degrees C), analyzed after opening of the original
      package, and consequently after 4 and 7 days. Results of the antioxidant capacity
      are expressed as the standard equivalents, that is, ascorbic acid in mmol/L. The
      highest mean value of the antioxidant capacity was found after opening of the
      original package in fruit-juice-enriched samples and totaled 9.793 mmol/L. This
      group revealed significant dependence (P < 0.05) not only on the storage time,
      but also temperature. In samples without added fruit juices containing
      preservatives the value was 0.428 mmol/L. This group showed significant
      dependence (P < 0.05) on the decrease of antioxidant capacity only when based on
      the storage time. Samples without fruit juices or preservatives showed
      significant decrease in the antioxidant capacity (P < 0.05) after 4 days of
      storage based on the storage time. The dependence on temperature was revealed
      only after 7 days of storage.

PMID- 22997492
TI  - Estimating elasticity for residential electricity demand in China.
AB  - Residential demand for electricity is estimated for China using a unique
      household level dataset. Household electricity demand is specified as a function
      of local electricity price, household income, and a number of social-economic
      variables at household level. We find that the residential demand for electricity
      responds rather sensitively to its own price in China, which implies that there
      is significant potential to use the price instrument to conserve electricity
      consumption. Electricity elasticities across different heterogeneous household
      groups (e.g., rich versus poor and rural versus urban) are also estimated. The
      results show that the high income group is more price elastic than the low income
      group, while rural families are more price elastic than urban families. These
      results have important policy implications for designing an increasing block
      tariff.

PMID- 22997493
TI  - Activated PTHLH coupling feedback phosphoinositide to G-protein receptor signal
      induced cell adhesion network in human hepatocellular carcinoma by systems
      theoretic analysis.
AB  - Studies were done on analysis of biological processes in the same high expression
      (fold change >=2) activated PTHLH feedback-mediated cell adhesion gene ontology
      (GO) network of human hepatocellular carcinoma (HCC) compared with the
      corresponding low expression activated GO network of no-tumor hepatitis/cirrhotic
      tissues (HBV or HCV infection). Activated PTHLH feedback-mediated cell adhesion
      network consisted of anaphase-promoting complex-dependent proteasomal ubiquitin
      dependent protein catabolism, cell adhesion, cell differentiation, cell-cell
      signaling, G-protein-coupled receptor protein signaling pathway, intracellular
      transport, metabolism, phosphoinositide-mediated signaling, positive regulation
      of transcription, regulation of cyclin-dependent protein kinase activity,
      regulation of transcription, signal transduction, transcription, and transport in
      HCC. We proposed activated PTHLH coupling feedback phosphoinositide to G-protein
      receptor signal-induced cell adhesion network. Our hypothesis was verified by the
      different activated PTHLH feedback-mediated cell adhesion GO network of HCC
      compared with the corresponding inhibited GO network of no-tumor
      hepatitis/cirrhotic tissues, or the same compared with the corresponding
      inhibited GO network of HCC. Activated PTHLH coupling feedback phosphoinositide
      to G-protein receptor signal-induced cell adhesion network included BUB1B, GNG10,
      PTHR2, GNAZ, RFC4, UBE2C, NRXN3, BAP1, PVRL2, TROAP, and VCAN in HCC from GEO
      dataset using gene regulatory network inference method and our programming.

PMID- 22997494
TI  - Sequence comparison alignment-free approach based on suffix tree and L-words
      frequency.
AB  - The vast majority of methods available for sequence comparison rely on a first
      sequence alignment step, which requires a number of assumptions on evolutionary
      history and is sometimes very difficult or impossible to perform due to the
      abundance of gaps (insertions/deletions). In such cases, an alternative alignment
      free method would prove valuable. Our method starts by a computation of a
      generalized suffix tree of all sequences, which is completed in linear time.
      Using this tree, the frequency of all possible words with a preset length L-L
      words--in each sequence is rapidly calculated. Based on the L-words frequency
      profile of each sequence, a pairwise standard Euclidean distance is then computed
      producing a symmetric genetic distance matrix, which can be used to generate a
      neighbor joining dendrogram or a multidimensional scaling graph. We present an
      improvement to word counting alignment-free approaches for sequence comparison,
      by determining a single optimal word length and combining suffix tree structures
      to the word counting tasks. Our approach is, thus, a fast and simple application
      that proved to be efficient and powerful when applied to mitochondrial genomes.
      The algorithm was implemented in Python language and is freely available on the
      web.

PMID- 22997495
TI  - Botulinum neurotoxin type A for the treatment of benign prostatic hyperplasia:
      randomized study comparing two doses.
AB  - PURPOSE: To assess the efficacy and safety of intraprostatic injection of two
      botulinum neurotoxin type A (BoNT-A) doses for the treatment of benign prostatic
      hyperplasia (BPH). MATERIALS AND METHODS: Men with symptomatic BPH who failed
      medical treatment were randomized to receive 100 U or 200 U of BoNT-A into the
      prostate. The International Prostatic Symptom Score (IPSS), maximum flow rate
      (Q(max)), post-void residual volume (PVR), PSA levels and prostate volume before
      injection and after 3 and 6 months were evaluated. Adverse events were compared
      between the groups. RESULTS: Thirty four patients were evaluated, including 17 in
      the BoNT-A 100 U group and 17 in the BoNT-A 200 U group. Baseline characteristics
      were similar in both groups. Both doses produced significant improvements in
      IPSS, Q(max) and PVR after 3 and 6 months and both doses promoted comparable
      effects. Prostate volume was affected by 200 U BoNT-A injection only after 6
      months of treatment. PSA levels were significantly affected in the 100 U group
      only after 6 months of treatment. In the 200 U group, PSA levels were
      significantly decreased after 3 and 6 months. The complication rate was similar
      in both groups. CONCLUSIONS: Efficacy and safety of both BoNT-A doses are similar
      for BPH treatment in the short term followup.

PMID- 22997496
TI  - Ultrasonograph and clinical quantitative characterization of tendinopathy by
      modified splitting in a goat model.
AB  - A tendinopathy is a clinical condition characterized by activity-related pain,
      focal tendons tenderness, and intratendinous imaging changes. This study
      characterizes a surgically induced tendinopathy in a goat model with a
      noninvasive in vivo longitudinal followup based on physical examination and US.
      Cross-sectional area (CSA) is the most objective feature for the evaluation of
      tendinopathy in correlation with clinical findings. The deep digital flexor
      tendon (DDFT) of the left hind limb of six goats was isolated and scarified by a
      modified splitting. Pain and lameness at walk and trot were evaluated. External
      width and thickness of tendon region were measured by calipers. CSA and the ratio
      lesion/tendon CSA were obtained at days 0, 7, 21, 42, and 84 by US. The highest
      value of global functional score was obtained at day 7, then decreased until day
      40 and was not significantly different from day 0 at the end of the study. The
      external width recovered a normal value at the end of the study, but the external
      thickness was still significantly increased (P < 0.05). Peritendinous oedema was
      observed at day 7, but intratendinous lesions were visible only at day 21 as a
      focal hypo to anechoic area. At day 84, two tendons still presented visible
      lesions. US examination was reproducible, specific, and provided complementary
      information to the global functional score. A standardized focal tendinopathy was
      induced in goats. This experimental model of focal tendinopathy could be used to
      study the effect of different treatments.

PMID- 22997497
TI  - Cation dependence, pH tolerance, and dosage requirement of a bioflocculant
      produced by Bacillus spp. UPMB13: flocculation performance optimization through
      kaolin assays.
AB  - A bioflocculant-producing bacterial strain with highly mucoid and ropy colony
      morphological characteristics identified as Bacillus spp. UPMB13 was found to be
      a potential bioflocculant-producing bacterium. The effect of cation dependency,
      pH tolerance and dosage requirement on flocculating ability of the strain was
      determined by flocculation assay with kaolin as the suspended particle. The
      flocculating activity was measured as optical density and by flocs formation. A
      synergistic effect was observed with the addition of monovalent and divalent
      cations, namely, Na+, Ca2+, and Mg2+, while Fe2+ and Al3+ produced inhibiting
      effects on flocculating activity. Divalent cations were conclusively demonstrated
      as the best cation source to enhance flocculation. The bioflocculant works in a
      wide pH range, from 4.0 to 8.0 with significantly different performances (P <
      0.05), respectively. It best performs at pH 5.0 and pH 6.0 with flocculating
      performance of above 90%. A much lower or higher pH would inhibit flocculation.
      Low dosage requirements were needed for both the cation and bioflocculant, with
      only an input of 50 mL/L for 0.1% (w/v) CaCl2 and 5 mL/L for culture broth,
      respectively. These results are comparable to other bioflocculants produced by
      various microorganisms with higher dosage requirements.

PMID- 22997499
TI  - Does thrombocyte size give us an idea about thrombocytosis etiology?
AB  - In the presence of a pathogenetic mutation in JAK2 or MPL, a differential
      diagnosis of essential thrombocythemia (ET) from reactive causes is relatively
      simple. However, in patients with suspected ET who lack JAK2 and MPL mutations,
      the exclusion of secondary causes is especially important. The study was aimed to
      explore the clinical application of particularly mean platelet volume (MPV),
      hemoglobin, red blood cell indices, white blood cell, serum iron profile, and C
      reactive protein level in the differential diagnosis of thrombocytosis. Medical
      records of 49 patients, consisting of reactive thrombocytosis (RT) and ET were
      retrospectively reviewed. The mean MPV level in RT group was 7.49 fL, and in ET
      group was 8.80 fL (P < 0.01). A cutoff point of <8.33 fL was found to have
      significant predictive value according to ROC curve analysis. This cutoff was
      associated with 83% positive predictive value (PPV) and 74% negative predictive
      value (NPV) in the diagnosis of ET and had a sensitivity of 65% and specificity
      of 89% for ET. Investigation of MPV is cheap, quick, and noninvasive, and may
      serve as a predictor of primary thrombocytosis. High sensitivity, specificity,
      PPV, and NPV enable this test an important tool and a possible surrogate marker
      in clinical practice.

PMID- 22997498
TI  - Oxytocin and the biopsychology of performance in team sports.
AB  - Little is known about the biopsychological underpinnings of expert performance in
      team sports. In this paper we show that there is a vast support for oxytocin as a
      neuropeptide involved in the encouragement of important processes linked to
      greater team performance in sport. We argue that oxytocin is related to
      biopsychological processes aimed at convergence of emotions and moods between
      people, and in doing so it is a critical neuropeptide involved in the shaping of
      important team processes in sport such as trust, generosity, altruism, cohesion,
      cooperation, and social motivation, and also envy and gloating. Future research
      should examine the role of oxytocin in these essential components of sport
      performance. In particular, the link between oxytocin, emotional contagion and
      the cultivation of experiences of positive emotions is a worthwhile line of
      investigation for sport participation and development as well as high performance
      in sport.

PMID- 22997500
TI  - NOD2 agonist promotes the production of inflammatory cytokines in VSMC in synergy
      with TLR2 and TLR4 agonists.
AB  - OBJECTIVE: To investigate the expression of NOD2 in human VSMCs, its role in the
      production of inflammatory cytokines in VSMC and the possible interaction of NOD2
      mediated signaling pathway with those mediated by TLR2 and TLR4. METHODS: Human
      coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone
      or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA
      expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8
      and TNF-alpha in the culture supernatants was determined by ELISA. VSMC
      proliferation ability was analyzed by MTT assay. RESULTS: MDP up regulated the
      expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the
      expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-alpha,
      and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and
      PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and
      TNF-alpha. CONCLUSION: The activation of NOD2-mediated innate immune signaling
      pathway can increase the proliferation ability of VSMC and induce the production
      of inflammatory cytokines in VSMC. It is also shown a synergistic effect with
      TLR2- and TLR4-mediated signaling pathways in this process.

PMID- 22997501
TI  - Levels of PAHs in the waters, sediments, and shrimps of Estero de Urias, an
      estuary in Mexico, and their toxicological effects.
AB  - PAHs were measured in water, sediment, and shrimps of Estero de Urias, an estuary
      in Sinaloa, Mexico, during the rainy and dry seasons, and analyzed for eleven
      PAHs routinely detected in samples. Phenanthrene was the most dominant congener
      in the water, sediment, and shrimp samples comprising about 38, 24, and 25%,
      respectively, of the eleven PAHs detected, followed by pyrene and naphthalene in
      water and sediment samples, and pyrene and fluorine in the shrimp samples. Total
      PAH concentrations ranged from 9 to 347 ng/L in water, 27 to 418 ng/g in
      sediments, and 36 to 498 ng/g in shrimps. The sources of contamination are
      closely related to human activities such as domestic and industrial discharge,
      automobile exhausts, and street runoff. High concentrations were also measured
      during the rainy season and during the first quarter of the year. Toxicity tests
      were also carried out, exposing fish embryos and juvenile shrimps to some of
      these PAHs. Fish embryos exposed to PAHs showed exogastrulation, while juvenile
      shrimps showed significantly lower growth rates than controls. DNA and protein
      alterations were also observed. These toxicity tests indicate that PAH
      concentrations measured could be dangerous to some aquatic organisms,
      particularly during early stages of development.

PMID- 22997502
TI  - Diversity of macro- and micronutrients in the seeds of lentil landraces.
AB  - Increasing the amount of bioavailable mineral elements in plant foods would help
      to improve the nutritional status of populations in developing countries. Legume
      seeds have the potential to provide many essential nutrients. It is important to
      have information on genetic variations among different lentil populations so that
      plant breeding programs can use new varieties in cross-breeding programs. The
      main objective of this study was to characterize the micro- and macronutrient
      concentrations of lentil landraces seeds collected from South-Eastern Turkey. We
      found impressive variation in the micro- and macroelement concentrations in 39
      lentil landraces and 7 cultivars. We investigated the relationships of traits by
      correlation analysis and principal component analysis (PCA). The concentrations
      of several minerals, particularly Zn, were positively correlated with other
      minerals, suggesting that similar pathways or transporters control the uptake and
      transport of these minerals. Some genotypes had high mineral and protein content
      and potential to improve the nutritional value of cultivated lentil. Cross
      breeding of numerous lentil landraces from Turkey with currently cultivated
      varieties could improve the levels of micro- and macronutrients of lentil and may
      contribute to the worldwide lentil quality breeding program.

PMID- 22997503
TI  - Prevalence of clinically significant extraosseous findings on unenhanced CT
      portions of 18F-fluoride PET/CT bone scans.
AB  - OBJECTIVE: Due to the frequently interrupted supply of (99m)Tc-methylene
      diphosphonate, the use of 18F-fluoride positron emission tomography
      (PET)/computed tomography (CT) has become more popular. The study aims to
      determine the percentage of extraosseous findings from the unenhanced CT portion
      of F 18F-fluoride PET/CT scans. MATERIALS AND METHODS: We retrospectively
      collected 18F-fluoride PET/CT studies between March 2010 and February 2011. The
      unenhanced CT portions of 18F-fluoride PET/CT were reviewed for each patient.
      Significant extraosseous findings related to malignancy from the unenhanced CT
      were recorded. RESULTS: A total of 158 patients (110 females, 48 males) were
      included in the study. Clinically significant extraosseous findings from the
      unenhanced CT were found in 43 patients (27.2%). Previously unknown extraosseous
      findings were identified in 17 patients (10.8%) after a review of the 18F
      fluoride PET/CT scan results. Most of the extraosseous findings were small
      pulmonary metastases or enlarged metastatic lymph nodes. CONCLUSION: It is not
      rare to identify new clinically significant extraosseous findings from the
      unenhanced CT of 18F-fluoride PET/CT studies. Therefore the clinical management
      of patients may be altered by the results, and a careful review of the unenhanced
      CT portion of 18F-fluoride PET/CT is mandatory.

PMID- 22997504
TI  - Is There a Place for Screening Flexible Sigmoidoscopy?
AB  - Flexible sigmoidoscopy is a valid screening tool for the early detection of
      colorectal cancer (CRC). Recently published long-term data from UKFSST, a
      randomized controlled trial, demonstrate a 33% reduction in colorectal cancer
      incidence and a 43% decrease in colorectal cancer mortality, with once-in-a
      lifetime screening. On the other hand, data from the NORCCAP trial with a similar
      protocol show no reduction in CRC incidence and only nonsignificant decrease in
      CRC mortality at 7 years. At best, flexible sigmoidoscopy can detect only 70% of
      cancers and polyps as it does not detect the 40% of proximal neoplasms which are
      not associated with a distal lesion. The advantage of flexible sigmoidoscopy over
      other screening modalities lies in its safety profile, patient tolerance, and
      overall acceptance. Its technical simplicity, short duration, and cost
      effectiveness advance its applicability to mass screening programs.

PMID- 22997505
TI  - TGFbeta1 Controls PPARgamma Expression, Transcriptional Potential, and Activity,
      in Part, through Smad3 Signaling in Murine Lung Fibroblasts.
AB  - Transforming growth factor beta1 (TGFbeta1) promotes fibrosis by, among other
      mechanisms, activating quiescent fibroblasts into myofibroblasts and increasing
      the expression of extracellular matrices. Recent work suggests that peroxisome
      proliferator-activated receptor gamma (PPARgamma) is a negative regulator of
      TGFbeta1-induced fibrotic events. We, however, hypothesized that antifibrotic
      pathways mediated by PPARgamma are influenced by TGFbeta1, causing an imbalance
      towards fibrogenesis. Consistent with this, primary murine primary lung
      fibroblasts responded to TGFbeta1 with a sustained downregulation of PPARgamma
      transcripts. This effect was dampened in lung fibroblasts deficient in Smad3, a
      transcription factor that mediates many of the effects of TGFbeta1.
      Paradoxically, TGFbeta1 stimulated the activation of the PPARgamma gene promoter
      and induced the phosphorylation of PPARgamma in primary lung fibroblasts. The
      ability of TGFbeta1 to modulate the transcriptional activity of PPARgamma was
      then tested in NIH/3T3 fibroblasts containing a PPARgamma-responsive luciferase
      reporter. In these cells, stimulation of TGFbeta1 signals with a constitutively
      active TGFbeta1 receptor transgene blunted PPARgamma-dependent reporter
      expression induced by troglitazone, a PPARgamma activator. Overexpression of
      PPARgamma prevented TGFbeta1 repression of troglitazone-induced PPARgamma
      dependent gene transcription, whereas coexpression of PPARgamma and Smad3
      transgenes recapitulated the TGFbeta1 effects. We conclude that modulation of
      PPARgamma is controlled by TGFbeta1, in part through Smad3 signals, involving
      regulation of PPARgamma expression and transcriptional potential.

PMID- 22997506
TI  - PPARgamma in Inflammatory Bowel Disease.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is member of a
      family of nuclear receptors that interacts with nuclear proteins acting as
      coactivators and corepressors. The colon is a major tissue which expresses
      PPARgamma in epithelial cells and, to a lesser degree, in macrophages and
      lymphocytes and plays a role in the regulation of intestinal inflammation.
      Indeed, both natural and synthetic PPARgamma ligands have beneficial effects in
      different models of experimental colitis, with possible implication in the
      therapy of inflammatory bowel disease (IBD). This paper will specifically focus
      on potential role of PPARgamma in the predisposition and physiopathology of IBD
      and will analyze its possible role in medical therapy.

PMID- 22997508
TI  - Hybrid particle swarm optimization and its application to multimodal 3D medical
      image registration.
AB  - In the area of medical image analysis, 3D multimodality image registration is an
      important issue. In the processing of registration, an optimization approach has
      been applied to estimate the transformation of the reference image and target
      image. Some local optimization techniques are frequently used, such as the
      gradient descent method. However, these methods need a good initial value in
      order to avoid the local resolution. In this paper, we present a new improved
      global optimization approach named hybrid particle swarm optimization (HPSO) for
      medical image registration, which includes two concepts of genetic algorithms
      subpopulation and crossover.

PMID- 22997507
TI  - Oxytocin and psychological factors affecting type 2 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to investigate the association of oxytocin
      with trait and state psychological factors in type 2 diabetic patients. METHODS:
      OXT and psychological variables were analyzed from 86 controlled diabetic
      patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled
      diabetic patients (HbA1c >= 7). Psychological characteristics were assessed with
      the Eysenck Personality Questionnaire (EPQ), while state psychological
      characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood
      samples were taken for measuring oxytocin in both subgroups during the initial
      phase of the study. One year later, the uncontrolled diabetic patients were
      reevaluated with the use of the same psychometric instruments. RESULTS: During
      the first evaluation of the uncontrolled diabetic patients, a statistically
      significant positive relationship between the levels of OXT and psychoticism in
      EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a
      statistically significant negative relationship between oxytocin and somatization
      (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating
      scale, was observed. During the second assessment, the values of OXT decreased
      when the patients managed to control their metabolic profile. CONCLUSIONS: The
      OXT is in association with psychoticism, somatization, and obsessionality may be
      implicated in T2DM.

PMID- 22997509
TI  - Urothelial carcinoma.

PMID- 22997510
TI  - Evaluation of Satisfaction and Axial Rigidity with Titan XL Cylinders.
AB  - The inflatable penile prosthesis (IPP) has high patient satisfaction rates and
      good mechanical reliability rates in multiple studies. The number one patient
      compliant at six months is penile length. Recently, new technique for aggressive
      sizing of the cylinders has been published on in the literature. One IPP company
      has produced a new product that has longer length cylinders (XL) than those
      available. However, traditionally long cylinders were felt to lack axial
      rigidity. Therefore, a prospective, multicenter, central IRB-approved, monitored
      study was performed on the new product to address these concerns. At 2 centers, a
      total of 17 patients underwent surgical implantation of these new XL cylinders.
      These patients were questioned for patient satisfaction and tested for axial
      rigidity using a Fastsize Erectile Quality Monitor. The results showed excellent
      patient satisfaction rates and great axial rigidity with the Fastsize Erectile
      Quality Monitor. The XL cylinders appear to give the IPP surgeon the ability to
      use longer cylinders with good patient satisfaction and great axial rigidity.

PMID- 22997511
TI  - How Do Low-Income Urban African Americans and Latinos Feel about Telemedicine? A
      Diffusion of Innovation Analysis.
AB  - Introduction. Telemedicine is promoted as a means to increase access to specialty
      medical care among the urban underserved, yet little is known about its
      acceptability among these populations. We used components of a diffusion of
      innovation conceptual framework to analyze preexperience perceptions about
      telemedicine to assess its appeal among urban underserved African Americans and
      Latinos. Methods. Ten focus groups were conducted with African American (n = 43)
      and Latino participants (n = 44) in both English and Spanish and analyzed for key
      themes. Results. Both groups perceived increased and immediate access to multiple
      medical opinions and reduced wait time as relative advantages of telemedicine.
      However, African Americans expressed more concerns than Latinos about
      confidentiality, privacy, and the physical absence of the specialist. This
      difference may reflect lower levels of trust in new health care innovations among
      African Americans resulting from a legacy of past abuses in the US medical system
      as compared to immigrant Latinos who do not have this particular historical
      backdrop. Conclusions. These findings have implications for important issues such
      as adoption of telemedicine, patient satisfaction, doctor-patient interactions,
      and the development and tailoring of strategies targeted to each of these
      populations for the introduction, marketing, and implementation of telemedicine.

PMID- 22997512
TI  - Prevalence and Risk Factors of Toxoplasma gondii Infection in Domestic Cats from
      the Tropics of Mexico Using Serological and Molecular Tests.
AB  - The aim of this study was to determine the prevalence and risk factors associated
      with Toxoplasma gondii infection in domestic cats using an indirect-ELISA (IgM
      and IgG) and PCR. Samples collected from 220 cats from Merida, Yucatan, Mexico,
      were analyzed. Cases were reported as acute or chronic. Cases when positive to
      IgM and IgG and PCR were considered as reactivated chronic infection. Risk
      factors (sex, age, body condition, diet access to hunting, and number of cats in
      home) were assessed with a multivariate analysis, 75.5% (166/220) of the cats
      were IgM and 91.8% (202/220) IgG-seropositive and 79% were PCR-positive
      (173/220). Number of cats per household and low body condition score were
      associated with reactivated chronic infection (P < 0.05). It is concluded that T.
      gondii is scattered in the studied population with several periods of
      reinfection, and therefore an environmental contamination with infecting oocysts
      exists and there are intrinsic associated factors in cats that increase the risk
      of becoming infected.

PMID- 22997513
TI  - Community-Based Research among Marginalized HIV Populations: Issues of Support,
      Resources, and Empowerment.
AB  - A research question was posed to us by a local HIV-resource organization
      interested in exploring the educational and service needs of those unreached. In
      order to properly address this inquiry, we developed a community-based
      participatory research by training peer-led volunteers to facilitate focus-group
      discussions within Aboriginal and refugees participants following an interview
      guide. We gathered Aboriginal people and refugees separated into three focus
      groups each, enrolling a total of 41 self-identified HIV-positive, 38 males. The
      discussions were tape recorded upon consent and lasted between 59 and 118
      minutes. We analyzed the thematic information collected interactively through
      constant comparison. The qualitative data leading to categories, codes, and
      themes formed the basis for the spatial representation of a conceptual mapping.
      Both groups shared similar struggles in living with HIV and in properly accessing
      local nonmedical HIV resources and discussed their concerns towards the need for
      empowerment and support to take control of their health.

PMID- 22997514
TI  - Diversity of mosquito vectors (Diptera: culicidae) in caxiuana, para, Brazil.
AB  - THIS PAPER PRESENTS A STUDY BASED ON ECOLOGICAL PARAMETERS REPRESENTED BY
      DIVERSITY AND RICHNESS INDICES APPLIED IN A COMMUNITY OF MOSQUITOES (DIPTERA:
      Culicidae), at the National Forest of Caxiuana, Melgaco municipality, state of
      Para, in the Brazilian Amazon. A total of 25,433 specimens of culicids were
      collected in the study, from five field collection periods, over 10 months,
      between 2005 and 2006. Specimens were collected in four heights of the forest
      (ground level, 8 m, 16 m, and 30 m-canopy). Diversity indices of Shannon and
      Berger-Parker were obtained, and indicators of dominance of species were
      calculated. The species Culex portesi was dominant in this site, representing
      about 84% of specimens. Measures of richness and similarity (Jaccard) were
      obtained for the five strata of time and four height levels. According to the
      richness estimator abundance-based covered estimator (ACE) the greatest value
      occurred in April (2006), considering the levels of height to 16 m and on the
      ground. The estimates obtained have shown quantitative parameters of mosquito
      populations in the region of the Forest of Caxiuana.

PMID- 22997515
TI  - Gap detection for genome-scale constraint-based models.
AB  - Constraint-based metabolic models are currently the most comprehensive system
      wide models of cellular metabolism. Several challenges arise when building an in
      silico constraint-based model of an organism that need to be addressed before
      flux balance analysis (FBA) can be applied for simulations. An algorithm called
      FBA-Gap is presented here that aids the construction of a working model based on
      plausible modifications to a given list of reactions that are known to occur in
      the organism. When applied to a working model, the algorithm gives a hypothesis
      concerning a minimal medium for sustaining the cell in culture. The utility of
      the algorithm is demonstrated in creating a new model organism and is applied to
      four existing working models for generating hypotheses about culture media. In
      modifying a partial metabolic reconstruction so that biomass may be produced
      using FBA, the proposed method is more efficient than a previously proposed
      method in that fewer new reactions are added to complete the model. The proposed
      method is also more accurate than other approaches in that only biologically
      plausible reactions and exchange reactions are used.

PMID- 22997516
TI  - Comparison Study of Metabolic Syndrome's Differences and Diagnostic Criteria's
      Applicability among Xingjiang Uighur, Kazak and Han Population.
AB  - Our paper is a study about metabolism syndrome (MS) incidence situations of
      different nationalities, including Uighur, Kazak and Han nationality in Xinjiang
      by means of a cross-sectional survey and compare differences and adaptabilities
      of applications of the diagnostic criteria for MS recommended by Adult Treatment
      Protocol III of National Cholesterol Education Program of America (ATP III),
      International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) in
      three groups of populations. Conclusion tell us, for Uighur population and Kazak
      population, IDF criterion and ATPIII criterion had a better consistence, and CDS
      criterion was worst. For Han population, CDS criterion and IDF criterion had a
      better consistence, and ATPIII criterion was worst. For the screening of MS
      incidence rate of Uighur and Kazak adult populations in Xinjiang region, ATPIII
      criterion was optimal, while CDS criterion was optimal for Han population.
      However, as for screening of clustering of multiple risk factors of MS, IDF
      criterion was better than other criteria for the three nationalities.

PMID- 22997517
TI  - DNA Repair and Cancer Therapy: Targeting APE1/Ref-1 Using Dietary Agents.
AB  - Epidemiological studies have demonstrated the cancer protective effects of
      dietary agents and other natural compounds isolated from fruits, soybeans, and
      vegetables on neoplasia. Studies have also revealed the potential for these
      natural products to be combined with chemotherapy or radiotherapy for the more
      effective treatment of cancer. In this paper we discuss the potential for
      targeting the DNA base excision repair enzyme APE1/Ref-1 using dietary agents
      such as soy isoflavones, resveratrol, curcumin, and the vitamins ascorbate and
      alpha-tocopherol. We also discuss the potential role of soy isoflavones in
      sensitizing cancer cells to the effects of radiotherapy. A comprehensive review
      of the dual nature of APE1/Ref-1 in DNA repair and redox activation of cellular
      transcription factors, NF-kappaB and HIF-1alpha, is also discussed. Further
      research efforts dedicated to delineating the role of APE1/Ref-1 DNA repair
      versus redox activity in sensitizing cancer cells to conventional treatment are
      warranted.

PMID- 22997518
TI  - Viral infection: an evolving insight into the signal transduction pathways
      responsible for the innate immune response.
AB  - The innate immune response is initiated by the interaction of stereotypical
      pathogen components with genetically conserved receptors for extracytosolic
      pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids.
      In multicellular organisms, this interaction typically clusters signal
      transduction molecules and leads to their activations, thereby initiating signals
      that activate innate immune effector mechanisms to protect the host. In some
      cases programmed cell death-a fundamental form of innate immunity-is initiated in
      response to genotoxic or biochemical stress that is associated with viral
      infection. In this paper we will summarize innate immune mechanisms that are
      relevant to viral pathogenesis and outline the continuing evolution of viral
      mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms
      of viral innate immune evasion provide significant insight into the pathways of
      the antiviral innate immune response of many organisms. Examples of relevant
      mammalian innate immune defenses host defenses include signaling to interferon
      and cytokine response pathways as well as signaling to the inflammasome.
      Understanding which viral innate immune evasion mechanisms are linked to
      pathogenesis may translate into therapies and vaccines that are truly effective
      in eliminating the morbidity and mortality associated with viral infections in
      individuals.

PMID- 22997519
TI  - Nasal outcomes of presurgical nasal molding in complete unilateral cleft lip and
      palate.
AB  - Objective. Short-term nasal forms following primary lip repair were compared
      between presurgical nasal molding and control groups. Aim. To compare nasal
      symmetry between patients that had nasal molding and lip repair with those that
      had only lip repair. Design. Retrospective case-control study Patients. Complete
      unilateral CL+P patients had basilar and frontal photographs at two time points:
      (1) initial (2) postsurgical. 28 nasal molding patients and 14 control patients
      were included. Intervention. Presurgical nasal molding was performed prior to
      primary lip repair in intervention group. No nasal molding was performed in
      control group. Hypothesis. Nasal molding combined with lip surgery repair
      according to the Millard procedure provides superior nasal symmetry than surgery
      alone for nostril height-width ratios and alar groove ratios. Statistics. Shapiro
      Wilk test of normality and Student's t-tests. Results. A statistically
      significant difference was found for postsurgical nostril height-width ratio (P <
      .05). No other statistically significant differences were found. Conclusions.
      Nasal molding and surgery resulted in more symmetrical nostril height-width
      ratios than surgery alone. Alar groove ratios were not statistically
      significantly different between groups perhaps because application of nasal
      molding was not early enough; postsurgical nasal splints were not utilized;
      overcorrection was not performed for nasal molding.

PMID- 22997520
TI  - In vitro inhibitory effect of clove essential oil and its two active principles
      on tooth decalcification by apple juice.
AB  - The dental erosion or decalcification of enamel is a significant clinical
      problem. Apple acidic beverages are thought to increase the potential for dental
      erosion. The purpose of this in vitro study was to investigate the effect of
      clove essential oil (CEO) and its active principles on tooth decalcification of
      apple juices. On GC-MS analysis, CEO showed a high content of eugenol (58.29%)
      and eugenyl acetate (19.10%). Teeth specimens were randomly divided into 5
      treatment groups: control, CEO, eugenol, eugenyl-acetate, and fluoride. The
      specimens were exposed for 24 h and were analyzed for calcium contents using
      Inductively Coupled Plasma with Optical Emission Spectroscopy (ICP-OES). Data
      were analyzed using student t-test (P < 0.05). CEO, eugenol, and eugenyl-acetate
      significantly decreased the decalcification of tooth by the apple juice to only
      17, 24, and 21 mgL(-1), respectively. Hemolytic activity on human erythrocytes
      was studied to exclude the possibility of further associated cytotoxicity. It was
      observed that the CEO and its two lead molecules inhibit the decalcification
      and/or promote the remineralization caused by the apple juices. The effect of the
      test compounds appears to be distinct like that of fluoride treatment. CEO may,
      therefore, serve to be a promising adjunct to fluoride in the treatment of root
      caries during minimally invasive therapy.

PMID- 22997521
TI  - Redox status and bioenergetics liaison in cancer and neurodegeneration.

PMID- 22997522
TI  - Ethical implications in the use of embryonic and adult neural stem cells.
AB  - The advent and growth of technological advances have led to new routes of
      knowledge. Thereby, we currently face new challenges. We have just started to get
      a glimpse of the structural and functional role of neural stem cells in
      differentiation and migration processes, the origin of synaptic networks, and
      subsequent readjustments in specific circuits. A whole range of treatment
      possibilities originates from this knowledge that potentially can be used for
      different neurological diseases in humans. Although this is an encouraging
      scenario, it implies that the human brain is the object of such study, as well as
      its potential manipulation and transplantation. It is, therefore, pertinent that
      ethical principles should be followed in such research to have proper balance
      between what can be done and what should be done, according to every specific
      context. Hence, it is wise to consider ethical implications in every research
      project, along with potential clinical applications, under the principle of
      causing no harm, following risk and benefit rules in decision making and with
      respect of the human condition as a priority.

PMID- 22997524
TI  - A method to assess the potential effects of air pollution mitigation on
      healthcare costs.
AB  - OBJECTIVE: The aim of this study was to develop a method to assess the potential
      effects of air pollution mitigation on healthcare costs and to apply this method
      to assess the potential savings related to a reduction in fine particle matter in
      Denmark. METHODS: The effects of air pollution on health were used to identify
      "exposed" individuals (i.e., cases). Coronary heart disease, stroke, chronic
      obstructive pulmonary disease, and lung cancer were considered to be associated
      with air pollution. We used propensity score matching, two-part estimation, and
      Lin's method to estimate healthcare costs. Subsequently, we multiplied the number
      of saved cases due to mitigation with the healthcare costs to arrive to an
      expression for healthcare cost savings. RESULTS: The potential cost saving in the
      healthcare system arising from a modelled reduction in air pollution was
      estimated at ?0.1-2.6 million per 100,000 inhabitants for the four diseases.
      CONCLUSION: We have illustrated an application of a method to assess the
      potential changes in healthcare costs due to a reduction in air pollution. The
      method relies on a large volume of administrative data and combines a number of
      established methods for epidemiological analysis.

PMID- 22997523
TI  - Regulation of injury-induced neurogenesis by nitric oxide.
AB  - The finding that neural stem cells (NSCs) are able to divide, migrate, and
      differentiate into several cellular types in the adult brain raised a new hope
      for restorative neurology. Nitric oxide (NO), a pleiotropic signaling molecule in
      the central nervous system (CNS), has been described to be able to modulate
      neurogenesis, acting as a pro- or antineurogenic agent. Some authors suggest that
      NO is a physiological inhibitor of neurogenesis, while others described NO to
      favor neurogenesis, particularly under inflammatory conditions. Thus, targeting
      the NO system may be a powerful strategy to control the formation of new neurons.
      However, the exact mechanisms by which NO regulates neural proliferation and
      differentiation are not yet completely clarified. In this paper we will discuss
      the potential interest of the modulation of the NO system for the treatment of
      neurodegenerative diseases or other pathological conditions that may affect the
      CNS.

PMID- 22997525
TI  - Coinhibitory molecules in autoimmune diseases.
AB  - Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune
      responses. Multiple studies indicate that the deficiency or mutation of
      coinhibitory molecules leads to the development of autoimmune diseases in mice
      and humans, indicating that the negative signals from coinhibitory molecules are
      crucial for the prevention of autoimmunity. In some conditions, the
      administration of decoy coinhibitory receptors (e.g., CTLA-4 Ig) or mAb against
      coinhibitory molecules suppresses the responses of self-reactive T cells in
      autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an
      attractive approach to induce tolerance in autoimmune diseases in humans where
      the disease-inducing self-antigens are not known. Particularly, administration of
      CTLA-4 Ig has shown great promise in animal models of autoimmune diseases and has
      been gaining increasing attention in clinical investigation in several autoimmune
      diseases in humans.

PMID- 22997526
TI  - Mitochondrial mutations are associated with atherosclerotic lesions in the human
      aorta.
AB  - Somatic mutations of the human mitochondrial genome can be a possible determinant
      of atherosclerosis. To test this possibility, forty mitochondrial mutations were
      analyzed in the present study in order to see which of these mutations might be
      associated with atherosclerosis. Ten mitochondrial mutations belonging to
      mitochondrial genes MT-RNR1 (rRNA 12S); MT-TL1 (tRNA-Leu, recognizes UUR); MT-TL2
      (tRNA-Leu, recognizes CUN); MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5,
      and 6, respectively, of NADH dehydrogenase); and MT-CYB (cytochrome b) were
      potentially associated with atherosclerosis. From 29% (2 of 7 aortic samples)
      upto 86% (6 of 7 aortic samples) of aortic samples had a significant difference
      between atherosclerotic plaques and unaffected tissue, with the respect to the
      level of heteroplasmy for each mutation. Further, the homogenates of affected and
      normal intimae of 22 aortas were compared to reveal the average level of
      heteroplasmy for the above-mentioned 10 mutations. For five mutations, the mean
      level of heteroplasmy was significantly different in atherosclerotic intimal
      homogenates in comparison with the unaffected tissue. These mutations were
      A1555G, C3256T, T3336C, G13513A, and G15059A. Thus, it was demonstrated that at
      least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5,
      and MT-CYB genes are associated with atherosclerosis.

PMID- 22997527
TI  - Effects of auricular acupressure on body weight parameters in patients with
      chronic schizophrenia.
AB  - Auricular acupressure is widely used in complementary and alternative medicine to
      reduce body weight, but little is known about the effects of auricular
      acupressure on body weight parameters in patients with chronic schizophrenia. The
      purpose of this study was to evaluate the effects of auricular acupressure on
      body weight parameters in patients with chronic schizophrenia. Eighty-six
      inpatients with schizophrenia were recruited from chronic wards in a psychiatric
      center. The participants were randomly divided into experimental (acupressure at
      4 acupuncture sites: hunger, stomach, shenmen and endocrine) and control groups,
      and body weight parameters were determined weekly for 8 weeks. There was no
      significant difference between the experimental and control groups in mean body
      weight, waist circumference, or body fat percentage at the pretest or during the
      entire 8-week study period. Therefore, auricular acupressure did not cause body
      weight reduction in patients with chronic schizophrenia.

PMID- 22997529
TI  - Antioxidant and Antityrosinase Activity of Flemingia macrophylla and Glycine
      tomentella Roots.
AB  - The antioxidant and antityrosinase activities of the water extract of Flemingia
      macrophylla root (WEFM) were investigated. The results showed that WEFM exhibited
      radical scavenging and reducing activities, as well as ferrous ion chelating
      property. In addition, WEFM also protected phospholipids against oxidation,
      indicating that WEFM could protect biomolecules from oxidative damage. Meanwhile,
      in the range of 50-100 MUg/mL, the tyrosinase inhibitory activity of WEFM
      increased with an increase in sample concentration and was superior to that of
      the water extract of Glycine tomentella root (WEGT). A high performance liquid
      chromatography analysis was used to determine the phenolic components, revealing
      that daidzin, daidzein, genistin, and genistein were present in WEFM and WEGT.
      Acting as an antioxidant and a tyrosinase inhibitor, these bioactive constituents
      could contribute to the protective effects of WEFM. Overall, the results showed
      that WEFM might serve as a natural antioxidant and tyrosinase inhibitor.

PMID- 22997528
TI  - Pharmacological effects of ginseng on liver functions and diseases: a minireview.
AB  - Ginseng, an ancient and famous medicinal herb in the Orient, has been used as a
      valuable tonic and for the treatment of various diseases including hepatic
      disorders. Ginseng saponins, commonly known as ginsenosides, are principal
      constituents and have believed to be responsible for multiple ginseng health
      benefits. There are more 40 ginsenosides isolated from ginseng. To date,
      treatment options for common liver diseases such as cirrhosis, fatty liver, and
      chronic hepatitis remain problematic. In this regard, ginseng extracts and
      individual ginsenosides have shown a wide array of beneficial role in the
      regulation of regular liver functions and the treatment of liver disorders of
      acute/chronic hepatotoxicity, hepatitis, hepatic fibrosis/cirrhosis,
      hepatocellular carcinoma, and so on in various pathways and mechanisms. In this
      paper, we first outline the pharmacological effects of ginseng and ginsenosides
      on the liver functions.

PMID- 22997530
TI  - Therapeutic Effects of Cortex acanthopanacis Aqueous Extract on Bone Metabolism
      of Ovariectomized Rats.
AB  - The aim of this study was to evaluate effects of aqueous extract from Cortex
      acanthopanacis (CAE) on osteoporosis rats induced by ovariectomy (OVX) using
      aqueous extract from Folium Epimedii (FEE) as positive control agent. Three-month
      old female rats that underwent OVX were treated with CAE. After 12 weeks, bone
      mineral density (BMD) and indices of bone histomorphometry of tibia were
      measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and
      receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were
      evaluated. In addition, the serum concentrations of osteocalcin (OC), interleukin
      1 beta (IL-1beta), interleukin-6 (IL-6), calcitonin (CT), and parathyroid hormone
      (PTH) were determined. Administration of CAE significantly prevented OVX-induced
      rats from gain of the body weight. Treatment with CAE increased bone mass
      remarkably and showed a significant inhibitory effect on bone resorption by
      downregulating significantly the expression of RANKL in tibia of OVX rats.
      Meanwhile, treatment of CAE significantly reduced serum level of IL-1beta and
      increased level of CT in OVX rats. This suggests that CAE has the potential to be
      used as an alternative therapeutic agent for postmenopausal osteoporosis.

PMID- 22997531
TI  - The benefit of a mechanical needle stimulation pad in patients with chronic neck
      and lower back pain: two randomized controlled pilot studies.
AB  - Objectives. The objective was to investigate whether a treatment with a needle
      stimulation pad (NSP) changes perceived pain and/or sensory thresholds in
      patients with chronic neck (NP) and lower back pain (BP). Methods. 40 patients
      with chronic NP and 42 patients with chronic BP were equally randomized to either
      treatment or waiting list control group. The treatment group self-administered a
      NSP over a period of 14 days. Pain ratings were recorded on numerical rating
      scales (NRSs). Mechanical detection thresholds (MDTs) and pressure pain
      thresholds (PPTs) were determined at the site of maximal pain and in the adjacent
      region, vibration detection thresholds (VDT) were measured at close spinal
      processes. The Northwick Park Neck Pain Questionnaire (NPQ) and the Oswestry
      Disability Index (ODI) were utilized for the NP and BP study, respectively.
      Results. NRS ratings were significantly reduced for the treatment groups compared
      to the control groups (NP: P = .021 and BP: P < .001), accompanied by a
      significant increase of PPT at pain maximum (NP: P = .032 and BP: P = .013).
      There was no effect on VDT and MDT. The NPQ showed also a significant
      improvement, but not the ODI. Conclusions. The mechanical NSP seems to be an
      effective treatment method for chronic NP and BP.

PMID- 22997532
TI  - The evolution of mindfulness-based physical interventions in breast cancer
      survivors.
AB  - Survivors of breast cancer are faced with a multitude of medical and
      psychological impairments during and after treatment and throughout their
      lifespan. Physical exercise has been shown to improve survival and recurrence in
      this population. Mind-body interventions combine a light-moderate intensity
      physical exercise with mindfulness, thus having the potential to improve both
      physical and psychological sequelae of breast cancer treatments. We conducted a
      review of mindfulness-based physical exercise interventions which included yoga,
      tai chi chuan, Pilates, and qigong, in breast cancer survivors. Among the
      mindfulness-based interventions, yoga was significantly more studied in this
      population as compared to tai chi chuan, Pilates, and qigong. The participants
      and the outcomes of the majority of the studies reviewed were heterogeneous, and
      the population included was generally not selected for symptoms. Yoga was shown
      to improve fatigue in a few methodologically strong studies, providing reasonable
      evidence for benefit in this population. Improvements were also seen in sleep,
      anxiety, depression, distress, quality of life, and postchemotherapy nausea and
      vomiting in the yoga studies. Tai chi chuan, Pilates, and qigong were not studied
      sufficiently in breast cancer survivors in order to be implemented in clinical
      practice.

PMID- 22997533
TI  - 7alpha-Hydroxy-beta-Sitosterol from Chisocheton tomentosus Induces Apoptosis via
      Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating
      ERK1/2 Activation.
AB  - In continuation of our interest towards the elucidation of apoptotic pathways of
      cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects
      of 7alpha-hydroxy-beta-sitosterol (CT1), a rare natural phytosterol oxide
      isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three
      different human tumor cell lines with minimal effects on normal cell controls,
      where cell viability levels were maintained >=80% upon treatment. Our results
      showed that cell death in MCF-7 breast tumor cells was achieved through the
      induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1
      was also found to increase proapoptotic Bax protein levels, while decreasing anti
      apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic
      pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3
      were also observed following CT1 exposure, confirming the involvement of
      cytochrome c-mediated apoptosis via the mitochondrial pathway. These results
      demonstrated the cytotoxic and apoptotic ability of 7alpha-hydroxy-beta
      sitosterol and suggest its potential anti-cancer use particularly on breast
      adenocarcinoma cells.

PMID- 22997534
TI  - Use of chinese herb medicine in cancer patients: a survey in southwestern china.
AB  - Chinese herb medicine (CHM) is the most commonly reported traditional Chinese
      medicine (TCM) modality. This study aimed to assess the prevalence and associated
      factors of CHM use in cancer patients in southwestern China. Cancer patients from
      eleven comprehensive cancer centers were asked to complete a structured
      questionnaire. Of 587 available replies, 53.0% used CHM. Multiple logistic
      regression analysis showed that educational level, stage of disease, duration of
      cancer since diagnosis, marital status, and previous use of CHM were strongly
      associated with CHM use after cancer diagnosis. The source of information about
      CHM was mainly from media and friends/family. CHM products were used without any
      consultation with a TCM practitioner by 67.5% of users. The majority used CHM to
      improve their physical and emotional well-beings and to reduce cancer therapy
      induced toxicities. About 4.5% patients reported side effects of CHM. This survey
      revealed a high prevalence of CHM use among cancer patients. However, these
      patients did not get sufficient consultation about the indications and
      contradictions of these drugs. It is imperative for oncologists to communicate
      with their cancer patients about the usage of CHM so as to avoid the potential
      side effects.

PMID- 22997535
TI  - The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP
      Treated Nonhuman Primate.
AB  - Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug
      induced dyskinesias. Mucuna pruriens endocarp powder (MPEP) contains several
      compounds including natural LD and has been reported to not cause drug-induced
      dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its
      underlying mechanistic actions are exclusively due to LD. We first compared MPEP
      with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each
      treatment ameliorated parkinsonism. We then compared the neuronal firing
      properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN)
      in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry
      alterations. Both treatments decreased SNR firing rate compared to HP state.
      However, LD+CD treatments significantly increased SNR bursting firing patterns
      that were not seen with MPEP+CD treatments. No significant changes were seen in
      STN firing properties. We then evaluated the effects of a water extract of MPEP.
      Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The
      distinctive neurophysiological findings in the basal ganglia and the ability to
      ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna
      pruriens acts through a novel mechanism that is different from that of LD.

PMID- 22997536
TI  - Impact of competitive flow on hemodynamics in coronary surgery: numerical study
      of ITA-LAD model.
AB  - Competitive flow from native coronary artery is considered as a major factor in
      the failure of the coronary artery bypass grafts. However, the physiological
      effects are not very clear. The aim is to research the impact of competitive flow
      caused by different left anterior descending (LAD) artery stenosis degrees on
      hemodynamics in internal thoracic artery (ITA) bypass graft. An idealized ITA-LAD
      model was built in CAD tools. The degree of the competitive flow was divided into
      five classes according to different LAD stenosis degrees: higher (no stenosis),
      secondary (30% stenosis), reduced (50% stenosis), lower (75% stenosis) and no
      competitive flow (fully stenosis). Finite volume method was employed for the
      numerical simulation. The flow velocity distributions, wall shear stress and
      oscillatory shear index were analyzed. Results showed that higher competitive
      flow in the bypass graft would produce unbeneficial wall shear stress
      distribution associating with endothelial dysfunction and subsequent graft
      failure. The coronary bypass graft surgery was preferred to be carried out when
      the LAD stenosis was higher than 75%.

PMID- 22997537
TI  - Identification of novel type III effectors using latent Dirichlet allocation.
AB  - Among the six secretion systems identified in Gram-negative bacteria, the type
      III secretion system (T3SS) plays important roles in the disease development of
      pathogens. T3SS has attracted a great deal of research interests. However, the
      secretion mechanism has not been fully understood yet. Especially, the
      identification of effectors (secreted proteins) is an important and challenging
      task. This paper adopts machine learning methods to identify type III secreted
      effectors (T3SEs). We extract features from amino acid sequences and conduct
      feature reduction based on latent semantic information by using latent Dirichlet
      allocation model. The experimental results on Pseudomonas syringae data set
      demonstrate the good performance of the new methods.

PMID- 22997538
TI  - A literature review of the numerical analysis of abdominal aortic aneurysms
      treated with endovascular stent grafts.
AB  - The purpose of this paper is to present the basic principles and relevant
      advances in the computational modeling of abdominal aortic aneurysms and
      endovascular aneurysm repair, providing the community with up-to-date state of
      the art in terms of numerical analysis and biomechanics. Frameworks describing
      the mechanical behavior of the aortic wall already exist. However, intraluminal
      thrombus nonhomogeneous structure and porosity still need to be well
      characterized. Also, although the morphology and mechanical properties of
      calcifications have been investigated, their effects on wall stresses remain
      controversial. Computational fluid dynamics usually assumes a rigid artery wall,
      whereas fluid-structure interaction accounts for artery compliance but is still
      challenging since arteries and blood have similar densities. We discuss
      alternatives to fluid-structure interaction based on dynamic medical images that
      address patient-specific hemodynamics and geometries. We describe initial
      stresses, elastic boundary conditions, and statistical strength for rupture risk
      assessment. Special emphasis is accorded to workflow development, from the
      conversion of medical images into finite element models, to the simulation of
      catheter-aorta interactions and stent-graft deployment. Our purpose is also to
      elaborate the key ingredients leading to virtual stenting and endovascular repair
      planning that could improve the procedure and stent-grafts.

PMID- 22997539
TI  - How the interval between prime and boost injection affects the immune response in
      a computational model of the immune system.
AB  - The immune system is able to respond more vigorously to the second contact with a
      given antigen than to the first contact. Vaccination protocols generally include
      at least two doses, in order to obtain high antibody titers. We want to analyze
      the relation between the time elapsed from the first dose (priming) and the
      second dose (boost) on the antibody titers. In this paper, we couple in vivo
      experiments with computer simulations to assess the effect of delaying the second
      injection. We observe that an interval of several weeks between the prime and the
      boost is necessary to obtain optimal antibody responses.

PMID- 22997540
TI  - A meshfree method for simulating myocardial electrical activity.
AB  - An element-free Galerkin method (EFGM) is proposed to simulate the propagation of
      myocardial electrical activation without explicit mesh constraints using a
      monodomain model. In our framework the geometry of myocardium is first defined by
      a meshfree particle representation that is, a sufficient number of sample nodes
      without explicit connectivities are placed in and inside the surface of
      myocardium. Fiber orientations and other material properties of myocardium are
      then attached to sample nodes according to their geometrical locations, and over
      the meshfree particle representation spatial variation of these properties is
      approximated using the shape function of EFGM. After the monodomain equations are
      converted to their Galerkin weak form and solved using EFGM, the propagation of
      myocardial activation can be simulated over the meshfree particle representation.
      The derivation of this solution technique is presented along a series of
      numerical experiments and a solution of monodomain model using a FitzHugh-Nagumo
      (FHN) membrane model in a canine ventricular model and a human-heart model which
      is constructed from digitized virtual Chinese dataset.

PMID- 22997542
TI  - RANDOM LASSO.
AB  - We propose a computationally intensive method, the random lasso method, for
      variable selection in linear models. The method consists of two major steps. In
      step 1, the lasso method is applied to many bootstrap samples, each using a set
      of randomly selected covariates. A measure of importance is yielded from this
      step for each covariate. In step 2, a similar procedure to the first step is
      implemented with the exception that for each bootstrap sample, a subset of
      covariates is randomly selected with unequal selection probabilities determined
      by the covariates' importance. Adaptive lasso may be used in the second step with
      weights determined by the importance measures. The final set of covariates and
      their coefficients are determined by averaging bootstrap results obtained from
      step 2. The proposed method alleviates some of the limitations of lasso, elastic
      net and related methods noted especially in the context of microarray data
      analysis: it tends to remove highly correlated variables altogether or select
      them all, and maintains maximal flexibility in estimating their coefficients,
      particularly with different signs; the number of selected variables is no longer
      limited by the sample size; and the resulting prediction accuracy is competitive
      or superior compared to the alternatives. We illustrate the proposed method by
      extensive simulation studies. The proposed method is also applied to a
      Glioblastoma microarray data analysis.

PMID- 22997541
TI  - Reliable and efficient approach of BOLD signal with dual Kalman filtering.
AB  - By introducing the conflicting effects of dynamic changes in blood flow, volume,
      and blood oxygenation, Balloon model provides a biomechanical compelling
      interpretation of the BOLD signal. In order to obtain optimal estimates for both
      the states and parameters involved in this model, a joint filtering (estimate)
      method has been widely used. However, it is flawed in several aspects (i)
      Correlation or interaction between the states and parameters is incorporated
      despite its nonexistence in biophysical reality. (ii) A joint representation for
      states and parameters necessarily means the large dimension of state space and
      will in turn lead to huge numerical cost in implementation. Given this knowledge,
      a dual filtering approach is proposed and demonstrated in this paper as a highly
      competent alternative, which can not only provide more reliable estimates, but
      also in a more efficient way. The two approaches in our discussion will be based
      on unscented Kalman filter, which has become the algorithm of choice in numerous
      nonlinear estimation and machine learning applications.

PMID- 22997543
TI  - Formation and regulation of adaptive response in nematode Caenorhabditis elegans.
AB  - All organisms respond to environmental stresses (e.g., heavy metal, heat, UV
      irradiation, hyperoxia, food limitation, etc.) with coordinated adjustments in
      order to deal with the consequences and/or injuries caused by the severe stress.
      The nematode Caenorhabditis elegans often exerts adaptive responses if
      preconditioned with low concentrations of agents or stressor. In C. elegans,
      three types of adaptive responses can be formed: hormesis, cross-adaptation, and
      dietary restriction. Several factors influence the formation of adaptive
      responses in nematodes, and some mechanisms can explain their response formation.
      In particular, antioxidation system, heat-shock proteins, metallothioneins,
      glutathione, signaling transduction, and metabolic signals may play important
      roles in regulating the formation of adaptive responses. In this paper, we
      summarize the published evidence demonstrating that several types of adaptive
      responses have converged in C. elegans and discussed some possible alternative
      theories explaining the adaptive response control.

PMID- 22997544
TI  - Overexpression of fatty-acid-beta-oxidation-related genes extends the lifespan of
      Drosophila melanogaster.
AB  - A better understanding of the aging process is necessary to ensure that the
      healthcare needs of an aging population are met. With the trend toward increased
      human life expectancies, identification of candidate genes affecting the
      regulation of lifespan and its relationship to environmental factors is
      essential. Through misexpression screening of EP mutant lines, we previously
      isolated several genes extending lifespan when ubiquitously overexpressed,
      including the two genes encoding the fatty-acid-binding protein and dodecenoyl
      CoA delta-isomerase involved in fatty-acid beta-oxidation, which is the main
      energy resource pathway in eukaryotic cells. In this study, we analyzed flies
      overexpressing the two main components of fatty-acid beta-oxidation, and found
      that overexpression of fatty-acid-beta-oxidation-related genes extended the
      Drosophila lifespan. Furthermore, we found that the ability of dietary
      restriction to extend lifespan was reduced by the overexpression of fatty-acid
      beta-oxidation-related genes. Moreover, the overexpression of fatty-acid-beta
      oxidation-related genes enhanced stress tolerance to oxidative and starvation
      stresses and activated the dFOXO signal, indicating translocation to the nucleus
      and transcriptional activation of the dFOXO target genes. Overall, the results of
      this study suggest that overexpression of fatty-acid-beta-oxidation-related genes
      extends lifespan in a dietary-restriction-related manner, and that the mechanism
      of this process may be related to FOXO activation.

PMID- 22997545
TI  - Prediction of an Epidemic Curve: A Supervised Classification Approach.
AB  - Classification methods are widely used for identifying underlying groupings
      within datasets and predicting the class for new data objects given a trained
      classifier. This study introduces a project aimed at using a combination of
      simulations and classification techniques to predict epidemic curves and infer
      underlying disease parameters for an ongoing outbreak.Six supervised
      classification methods (random forest, support vector machines, nearest neighbor
      with three decision rules, linear and flexible discriminant analysis) were used
      in identifying partial epidemic curves from six agent-based stochastic
      simulations of influenza epidemics. The accuracy of the methods was compared
      using a performance metric based on the McNemar test.The findings showed that:
      (1) assumptions made by the methods regarding the structure of an epidemic curve
      influences their performance i.e. methods with fewer assumptions perform best,
      (2) the performance of most methods is consistent across different individual
      based networks for Seattle, Los Angeles and New York and (3) combining
      classifiers using a weighting approach does not guarantee better prediction.

PMID- 22997547
TI  - A simple and efficient protocol for the mass propagation of Cymbidium mastersii:
      an ornamental orchid of Northeast India.
AB  - BACKGROUND AND AIMS: Cymbidium mastersii is an epiphytic orchid distributed
      mainly in Northeast India. Owing to its high commercial value in the
      floricultural industry, natural populations are under threat from over
      exploitation. Mass propagation provides an alternative means of satisfying the
      demand. Unfortunately, conventional propagation is slow and difficult, suggesting
      in vitro methods for mass multiplication may be more appropriate. The objective
      of this study was to develop an efficient protocol. METHODOLOGY AND PRINCIPAL
      RESULTS: FOUR NUTRIENT MEDIA WERE EVALUATED FOR SEED GERMINATION AND EARLY
      PROTOCORM DEVELOPMENT: Murashige and Skoog (MS), half-strength MS, Knudson 'C'
      (KC), and Vacin and Went (VW). In addition, the effects of plant growth
      regulators 6-benzylaminopurine (BAP), kinetin (KN), alpha-naphthalene acetic acid
      (NAA) and indole-3-butyric acid (IBA) were studied alone and in combination. The
      maximum percentage seed germination (93.58 +/- 0.56) was obtained in MS basal
      medium after 8-9 weeks of culture. Secondary protocorms (protocorm-like bodies)
      were developed from primary protocorms on MS medium fortified with different
      concentrations and combinations of cytokinins (BAP and KN) and auxins (NAA and
      IBA). The highest numbers of secondary protocorms (20.55 +/- 0.62)/primary
      protocorms were obtained in MS medium supplemented with 5.0 uM BAP and 2.5 uM
      NAA. The most effective auxin source promoting root production (7.46 +/- 0.09 per
      shoot) was 10.0 uM IBA. The plants were acclimatized effectively (survival
      percentage 88 %) in a greenhouse using a rooting medium of crushed sterile brick
      and charcoal (1: 1v/v) and vermicompost (leaf litter + cow dung, 1: 1v/v).
      CONCLUSIONS: An efficient protocol was established for in vitro propagation of C.
      mastersii using seed as the starting material. The percentage seed germination
      varied with the composition of the nutrient media and was highest in full
      strength MS basal medium. The number of secondary protocorms that developed from
      primary protocorms was increased by the addition of 5.0 uM BAP and 2.5 uM NAA. In
      vitro raised plantlets acclimatized in a greenhouse were closely similar to the
      mother plants in morphology.

PMID- 22997546
TI  - EVALUATION OF HOW CIGARETTE SMOKE IS A DIRECT RISK FACTOR FOR ALZHEIMER'S
      DISEASE.
AB  - Cigarette smoking is a risk for Alzheimer's disease (AD), the pathological
      hallmark of which is amyloid-beta (Abeta) brain deposits. We found the adjusted
      risk of AD was significantly increased among medium level smokers (RR = 2.56; 95%
      CI = 1.65-5.52), with an even higher risk in the heavy smoking group (RR = 3.03;
      95% CI = 1.25-4.02). This systematic review and original data further support
      this association. We searched Pubmed, Google scholar, and PsyINFO for original
      population study articles, meta-analyses, and reviews published between 1987 and
      2011. Some studies were excluded due to design flaws including survivor bias. We
      performed analyses of: 1) amyloid precursor protein (APP) processing in N2a cells
      overexpressing Swedish mutant APP (SweAPP N2a) exposed to cigarette smoke
      condensate (CSC), 2) microglial inflammatory response to CSC, and 3) CSC exposed
      microglial phagocytosis of Abeta(1-42). CSC significantly promotes neuronal Abeta
      generation, increases microglial IL-1beta and TNF-alpha production, and decreases
      microglial Abeta(1-42) phagocytosis. The mechanism underlying the epidemiological
      association of cigarette smoking with AD might involve the effect of cigarette
      smoke on APP processing, a reduction of Abeta clearance by microglia, and/or an
      increased microglial proinflammatory response. In vivo studies are required to
      fully elucidate how cigarette smoke promotes AD.

PMID- 22997548
TI  - MHC genotype and near-deterministic mortality in grey seals.
AB  - The Major Histocompatability Complex (MHC) is one of the best known and best
      characterised components of the immune system, yet its functions remain somewhat
      enigmatic, including both anti-pathogen activity and kin recognition. To explore
      the importance of the MHC relative to literally hundreds of other components of
      the immune system, we compared MHC genotype frequencies between pups and adults
      in the grey seal (Halichoerus grypus), one of many marine mammals that exhibit
      low allelic diversity. We find that one allele is strongly associated with pup
      survival, pups being more likely to be found dead if they lack it, while total
      allele number is a remarkably strong predictor of survivorship to adulthood. We
      estimate that approximately 70% of mortality can be attributed to the MHC. Our
      study therefore shows that low MHC allele diversity belies its critical role in
      determining whether a weaned pup negotiates disease to become a breeding adult.

PMID- 22997549
TI  - Less than 5 Netrin-1 molecules initiate attraction but 200 Sema3A molecules are
      necessary for repulsion.
AB  - Guidance molecules, such as Sema3A or Netrin-1, induce growth cone (GC) repulsion
      or attraction. In order to determine the speed of action and efficiency of these
      guidance cues we developed an experimental procedure to deliver controlled
      amounts of these molecules. Lipid vesicles encapsulating 10-10(4) molecules of
      Sema3A or Netrin-1 were manipulated with high spatial and temporal resolution by
      optical tweezers and their photolysis triggered by laser pulses. Guidance
      molecules released from the vesicles diffused and reached the GC membrane in a
      few seconds. Following their arrival, GCs retracted or grew in 20-120 s. By
      determining the number of guidance molecules trapped inside vesicles and
      estimating the fraction of guidance molecules reaching the GC, we show that the
      arrival of less than 5 Netrin-1 molecules on the GC membrane is sufficient to
      induce growth. In contrast, the arrival of about 200 Sema3A molecules is
      necessary to induce filopodia repulsion.

PMID- 22997550
TI  - Is coaching experience associated with effective use of timeouts in basketball?
AB  - Experience is an important asset in almost any professional activity. In
      basketball, there is believed to be a positive association between coaching
      experience and effective use of team timeouts. Here, we analyze both the extent
      to which a team's change in scoring margin per possession after timeouts deviate
      from the team's average scoring margin per possession-what we called timeout
      factor, and the extent to which this performance measure is associated with
      coaching experience across all teams in the National Basketball Association over
      the 2009-2012 seasons. We find that timeout factor plays a minor role in the
      scoring dynamics of basketball. Surprisingly, we find that timeout factor is
      negatively associated with coaching experience. Our findings support empirical
      studies showing that, under certain conditions, mentors early in their careers
      can have a stronger positive impact on their teams than later in their careers.

PMID- 22997551
TI  - COMT Val158Met polymorphism interacts with stressful life events and parental
      warmth to influence decision making.
AB  - Both genetic and environmental factors have been shown to influence decision
      making, but their relative contributions and interactions are not well
      understood. The present study aimed to reveal possible gene-environment
      interactions on decision making in a large healthy sample. Specifically, we
      examined how the frequently studied COMT Val(158)Met polymorphism interacted with
      an environmental risk factor (i.e., stressful life events) and a protective
      factor (i.e., parental warmth) to influence affective decision making as measured
      by the Iowa Gambling Task. We found that stressful life events acted as a risk
      factor for poor IGT performance (i.e., high reward sensitivity) among Met
      carriers, whereas parental warmth acted as a protective factor for good IGT
      performance (i.e., higher IGT score) among Val/Val homozygotes. These results
      shed some new light on gene-environment interactions in decision making, which
      could potentially help us understand the underlying etiology of several
      psychiatric disorders associated with decision making impairment.

PMID- 22997552
TI  - The competitiveness versus the wealth of a country.
AB  - Politicians world-wide frequently promise a better life for their citizens. We
      find that the probability that a country will increase its per capita GDP (gdp)
      rank within a decade follows an exponential distribution with decay constant
      lambda = 0.12. We use the Corruption Perceptions Index (CPI) and the Global
      Competitiveness Index (GCI) and find that the distribution of change in CPI (GCI)
      rank follows exponential functions with approximately the same exponent as
      lambda, suggesting that the dynamics of gdp, CPI, and GCI may share the same
      origin. Using the GCI, we develop a new measure, which we call relative
      competitiveness, to evaluate an economy's competitiveness relative to its gdp.
      For all European and EU countries during the 2008-2011 economic downturn we find
      that the drop in gdp in more competitve countries relative to gdp was
      substantially smaller than in relatively less competitive countries, which is
      valuable information for policymakers.

PMID- 22997554
TI  - Accuracy of Various Iron Parameters in the Prediction of Iron Deficiency Anemia
      among Healthy Women of Child Bearing Age, Saudi Arabia.
AB  - BACKGROUND: Iron deficiency is still considered the most common nutritional
      deficiency worldwide and the most significant negative consequence of iron
      deficiency is iron deficiency anemia (IDA). This study elucidates if IDA among
      healthy women of child bearing age could be predicted by various iron parameters,
      using serum ferritin as a gold standard. METHODS: Between January and June 2009
      at primary care clinics of a teaching hospital in Saudi Arabia, 112 anemic
      (Hemoglobin = 120 g/l) subjects participated in the study. Mean corpuscular
      volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin
      concentration (MCHC), red blood cell distribution width (RDW), serum ferritin,
      and hemoglobin electrophoresis were obtained from all participants. Receiver
      operator characteristic (ROC) curves were used to assess the accuracy of various
      iron parameters. RESULTS: With respect to the serum ferritin, the best predictive
      cut-off value of MCV, MCH and RDW at the most optimal were 76 fl (ROC
      curve=0.768), 24 Pg (ROC curve=0.72) and 16.1% (ROC curve=0.711), respectively.
      MCHC was not significant in predicting the iron deficiency in these patients.
      CONCLUSION: IDA can be predicted among women of child bearing age using complete
      blood count test. MCV, MCH and RDW are the iron parameters of complete blood
      count test, which is a cost effective, easily accessible and could be useful tool
      in areas with limited resources and a high prevalence of the disease.

PMID- 22997553
TI  - Nitric oxide rescues thalidomide mediated teratogenicity.
AB  - Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb
      deformities in thousands of babies. Recently the drug was revived because of its
      therapeutic potential; however the search is still ongoing for an antidote
      against thalidomide induced limb deformities. In the current study we found that
      nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and
      zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number
      of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish
      embryos respectively. NO prevents limb deformities by promoting angiogenesis,
      reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We
      conclude that NO secures angiogenesis in the thalidomide treated embryos to
      protect them from deformities.

PMID- 22997555
TI  - Occupational Exposure to Blood and Body Fluids among Health Care Workers in
      Teaching Hospitals in Tehran, Iran.
AB  - BACKGROUND: Health care workers (HCWs) are vulnerable populations for infection
      with blood borne pathogens. This study was conducted to determine occupational
      exposure to blood and body fluids among HCWs in teaching hospitals in Tehran,
      Iran. METHODS: A self-structures questionnaire was used to study 650 HCWs during
      2006 -2007 in some teaching hospitals in Tehran, Iran. RESULTS: occupational
      exposure to blood and body fluids to blood and body fluids of patients was
      noticed in 53.4%. Recapping was the most common cause of niddle stick injuries
      (26.5%) and 19.9% of HCWs with a history of needlestick or mucosal exposure had
      sought medical advice from a specialist, 79.4% of these visited a doctor in the
      first 24 hours after exposure. Twenty percent of people with a history of
      needlestick or mucosal exposure to human immune deficiency virus positive
      (HIV(+)) patients received post-exposure prophylaxis and 46.7% tested themselves
      for seroconversion. 25.8% of HCWs with a history of needlestick or mucosal
      exposure with HBsAg(+) patients received hepatitis B immunoglobuline (HBIG), all
      of these had received it in the first 72 hours after exposure. History of
      vaccination, and reassurance about the effective serum antibody titer was the
      most frequent reason mentioned in case the individuals did not receive HBIG
      (56.5%). CONCLUSION: There is a need for further research to investigate why many
      HCWs do not take prophylactic and essential actions after needle stick or mucosal
      exposure to body fluids of infected patients.

PMID- 22997557
TI  - Factors influencing range of motion after total knee arthroplasty.
AB  - BACKGROUND: The range of motion after a total knee arthroplasty is an important
      clinical outcome affecting the life of the patient. The aim of this study was to
      determine the most important factors influencing the postoperative knee flexion
      in Tehran, Iran. METHODS: Between July 2007 and January 2009, on 95 cases of
      total knee joint replacement (89 patients), who were followed for 1 year
      postoperatively, the risk factors were assessed. Patient demographics (sex, age,
      body mass index, previous surgery, preoperative Knee Society System score, and
      preoperative range of motion) as well as radiographic measurement for
      preoperative tibiofemoral angle were statistically analyzed and the probable
      predictors entered into a linear regression model. RESULTS: Univariate analysis
      showed that age, preoperative flexion angle, preoperative flexion arc and
      preoperative tibiofemoral angle had significant correlation with the
      postoperative flexion angle. The linear regression model on the other hand
      revealed that preoperative flexion angle and preoperative tibiofemoral angle were
      the true predictors of the postoperative flexion angle with coefficients of 0.64
      and -0.21, respectively. CONCLUSION: Better range of motion before the surgery
      with a lower tibiofemoral varus/valgus angle were more likely to result in a
      better range of motion after the surgery, suggesting that an appropriate timing
      for the surgery when the knee joint is still in a better function can lead to a
      better outcome.

PMID- 22997556
TI  - Genotypic Analysis of E. coli Strains Isolated from Patients with Cystitis and
      Pyelonephritis.
AB  - BACKGROUND: Urinary tract infection is the most common health problem affecting
      millions of people each year, mainly caused by a large genetically heterogeneous
      group of Escherichia coli called uropathogenic E. coli This study investigates
      the genotypic analysis of E. coli strains isolated from patients with cystitis
      and pyelonephritis. METHODS: During 2008-2009, 90 E. coli strains were analyzed,
      consisting of 48 isolates causing pyelonephritis in children and 42 isolates
      causing cystitis. Having identified the strains by standard methods, they were
      subtyped by pulsed field gel electrophoresis (PFGE) and their corresponding
      patterns were compared using dendrogram. RESULTS: Sixty five PFGE profiles were
      obtained from the genome of E. coli strains by this genotyping method. Thirty six
      and thirty three patterns were obtained for pyelonephritis and cystitis,
      respectively. Most strains exhi-bited twelve and thirteen bands and the patterns
      with eight or nineteen bands had the lowest rate. Genome sizes of the strains
      were between 1610-4170 kbp. CONCLUSION: With due attention to these results,
      genetic patterns showed that the strains had different clonalities and it could
      be suggested in some cases that the strains causing pyelonephritis or cystitis
      have common patterns and different diseases could be explained by different gene
      factors.

PMID- 22997558
TI  - Longer years of practice and higher education levels promote infection control in
      Iranian dental practitioners.
AB  - BACKGROUNDS: Infection control is one of the primary responsibilities of dental
      health care personnel. The purpose of this study was to evaluate whether the
      infection control practices of Iranian dentists and dental nurses working in
      governmental dental health care centers were influenced by their educational
      level and years of practice. METHODS: This cross-sectional analytical study was
      completed in 2009, and it included 63 Iranian dental practitioners. Infection
      control knowledge was evaluated with a self-administered questionnaire, and
      infection control practices were evaluated with a checklist of questions by
      observation with one researcher. RESULTS: The dental practitioners in Mashad had
      a low level of infection control knowledge. Dental personnel with a higher
      educational level had significantly greater knowledge than those with less
      education. Additionally, dental personnel who had more years of practice had a
      greater knowledge of infection control. CONCLUSION: Since dental practitioners
      working in Mashad governmental dental health care centers with fewer years of
      practice and less educational level had a low level of infection control
      knowledge, we recommend a continuing educational program for this group and
      dental nurses.

PMID- 22997559
TI  - Perinatal outcome of pregnancies complicated by immune thrombocytopenia.
AB  - BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder that leads to
      premature destruction of antibody-coated platelets. This study evaluated
      perinatal outcome and medications used for pregnancies complicated by ITP.
      METHODS: Medical records of 132 pregnancies belonged to 125 parturients with ITP
      who delivered between March 2001 and January 2011 were reviewed. Cases were
      included if diagnosed before pregnancy or if their platelet counts (PCs) were
      less than 80,000/uL during pregnancy without any other cause. Maternal and fetal
      outcomes were compared. RESULTS: Fifty six mothers (42.1%) had PC<50,000, 18
      women (13.5%) developed preeclampsia and 15 (11.3%) were diabetics.
      Corticosteroid was used for120 cases (90.9%) and intravenous immunoglobulin for
      14 women (10.5%). PCs of 114 neonates were available in the charts and 84 (83.2%)
      had PC>150,000/uL. Three neonates (2.3%) had PC<50 000, 31 neonates (23.3%) had
      preterm births and 32 (24.1%) needed NICU admissions. Fifty seven cases of ITP
      (43.2%) were diagnosed before pregnancy and 75 (56.8%) were diagnosed during
      pregnancy. There were 2 intrauterine fetal deaths and higher NICU admissions, 20
      (34.48%) versus 12 (16%) in the first group (p=0.01). CONCLUSION: Perinatal
      outcome of pregnancies with ITP is generally good. However neonates born from
      parturients with chronic ITP needed more NICU admissions.

PMID- 22997560
TI  - Major Dietary Patterns among Female Adolescent Girls of Talaat Intelligent
      Guidance School, Tabriz, Iran.
AB  - BACKGROUND: Increasingly nutritional experts express the necessity of research on
      dietary patterns to identify numerous modifiable risk factors of disease. This
      study was conducted to identify major dietary patterns among adolescent girls in
      Talaat intelligent guidance school, Tabriz, Iran. METHODS: Among 257 adolescent
      girls aged 11-15 years, usual dietary intakes were assessed using a 162-item semi
      quantitative food frequency questionnaire (FFQ). Factor analysis was used to
      identify major dietary patterns in this Turkish population. RESULTS: We
      identified 6 major dietary patterns:(1) Western pattern high in pizza, meats and
      fruit juice; (2) Sweat junk foods pattern high in dried fruits, jams, honey and
      sugar; (3) Asian pattern high in legumes, potato and other vegetables; (4) Salty
      junk foods pattern high in carrot, puffs and potato chips and (6) Iranian
      traditional dietary pattern high in hydrogenated fats, garlic and broth.
      CONCLUSION: Our findings suggested that among the 6 major dietary patterns, Asian
      like food was the healthiest one.

PMID- 22997561
TI  - The effect of health belief model educational program and jogging on control of
      sugar in type 2 diabetic patients.
AB  - BACKGROUND: Researchers believe that most of diabetic patients are not
      necessarily aware of the role of exercises, especially jogging in controlling
      their disease. The purpose of this study was to evaluate the effect of
      educational program and jogging based on health belief model (HBM) on sugar
      control in type 2 diabetic patients. METHODS: One hundred diabetic (type 2)
      patients were involved in this prospective quasi-experimental interventional
      study. Patients were randomly divided into two groups of experimental and
      control. Data was collected using a questionnaire based on the HBM model, a check
      list for patient's practices and a check list for recording the patient's
      hemoglobin (HbA1C) and fasting blood sugar (FBS) levels. RESULTS: Our findings
      indicated that after intervention, there was a significant difference between the
      mean score of the HBM model variables (susceptibility, severity, benefit and
      perceived obstacles,) in the experimental group compared to the control group.
      Additionally, behavioral jogging, level of HbA1C and FBS levels improved
      significantly among the experimental group when compared to the control group.
      CONCLUSION: Applying the HBM model was found to be a very effective means for
      developing an educational program of jogging for diabetics, in order to control
      their blood sugar.

PMID- 22997562
TI  - Isolated renal mucormycosis after liver transplantation:an unusual case report.
AB  - Mucormycosis is a rare complication of immunosuppression. Most of the reported
      cases have been rhinocerebral or disseminated. Isolated renal involvement is
      extremely rare and until now less than 30 patients have been reported in the
      English literature. Isolated renal mucormycosis with renal artery rupture in a
      liver transplant patient has not been reported so far. Herein we report an
      extremely rare case of isolated renal mucormycosis in a liver transplant patient
      who was successfully treated with nephrectomy.

PMID- 22997563
TI  - Food habits in atopic patients in Iranian children.

PMID- 22997564
TI  - Investigation of Relationship between Hepatitis B Virus and Gastric
      Adenocarcinoma.

PMID- 22997565
TI  - Relationship between Cardiorespiratory Fitness and Cardiovascular Diseases Risk
      Factors in Iranian Children.

PMID- 22997566
TI  - Traumatic porencephaly with strabismus: a case report.

PMID- 22997567
TI  - Intravitreal fluorinated gas preference and occurrence of rare ischemic
      postoperative complications after pars plana vitrectomy: a survey of the american
      society of retina specialists.
AB  - Objective. To perform a survey of the American Society of Retina Specialists
      (ASRS) regarding the use of vitreous cavity fluorinated gas as an adjunct to pars
      plana vitrectomy for retinal detachment or macular hole repair. Methods. A
      multiple-choice online questionnaire was administered to members of ASRS.
      Physician experience, gas preference for vitrectomy, and categorical estimate of
      observation of blinding postoperative ischemic events were recorded. Results. 282
      questionnaires were completed. Mean years in vitreoretinal practice were 15 +/-
      10. A decrease in yearly vitrectomy volume was associated with increased number
      of years in practice (P = 0.011). Greater than 95% of respondents preferred
      fluorinated gas to air alone for both retinal detachment and macular hole repair.
      38% of respondents reported at least one observation of a blinding ischemic
      postoperative event. Overall estimated incidence of blinding postoperative
      ischemic event was 0.06 events/year in practice. Conclusions. Currently, C3F8 and
      SF6 are the postoperative gas preference for ASRS respondents, in contrast to
      previous North American surveys. The occurrence of blinding ischemic events
      appears unrelated to number of years in practice, was reported by less than half
      of those surveyed, and has occurred at an infrequent rate of approximately once
      for every ten years of practice for those observing the phenomena.

PMID- 22997568
TI  - Polyamine-Induced Rapid Root Abscission in Azolla pinnata.
AB  - Floating ferns of the genus Azolla detach their roots under stress conditions, a
      unique adaptive response termed rapid root abscission. We found that Azolla
      pinnata plants exhibited dose-dependent rapid root abscission in response to the
      polyamines spermidine and spermine after a substantial time lag (>20 min). The
      duration of the time lag decreased in response to high pH and high temperature
      whereas high light intensity increased the time lag and markedly lowered the rate
      of abscission. The oxidation products of polyamines, 1,3-diaminopropane, beta
      alanine and hydrogen peroxide all failed to initiate root abscission, and
      hydroxyethyl hydrazine, an inhibitor of polyamine oxidase, did not inhibit
      spermine-induced root abscission. Exposure of A. pinnata to the polyamines did
      not result in detectable release of NO and did not affect nitrite-dependent NO
      production. The finding of polyamine-induced rapid root abscission provides a
      facile assay for further study of the mode of action of polyamines in plant
      stress responses.

PMID- 22997569
TI  - The Association between Self-Reported Energy Intake and Intra-Abdominal Adipose
      Tissue in Perimenopausal Women.
AB  - We have previously shown that physical activity predicts intra-abdominal adipose
      tissue (IAT), but it is unknown whether energy intake predicts IAT independently
      of physical activity in a community-based, naturalistic environment. The
      association of energy intake with IAT was explored cross-sectionally in women,
      recruited between 2002 and 2005 for a study of fat patterning in midlife. IAT at
      L(4)-L(5) vertebral interspace was assessed by computed tomography, energy intake
      by the Block Food Frequency Questionnaire, and physical activity by the Kaiser
      Physical Activity Survey. Linear regression models were used for the principal
      analyses. Among the 257 women, 48% were African American and 52% were Caucasian.
      Women were 52 +/- 3 years old, and 49% were postmenopausal. Every 500 kcal
      increase in energy intake was associated with a 6% higher IAT (P = 0.02),
      independent of physical activity (P = 0.02), after adjustment for ethnicity,
      menopausal status, age, smoking, income, and DXA-assessed percent body fat.
      Energy intake had a significant interaction with ethnicity (P = 0.02), but not
      with physical activity. Models using the IAT to subcutaneous abdominal adipose
      tissue ratio as an outcome had similar associations. In conclusion, self-reported
      EI was associated with preferential IAT accumulation in midlife women,
      independent of physical activity. This association was significantly stronger in
      Caucasian than African American women. Future longitudinal studies are needed to
      explore lifestyle predictors of IAT accumulation during the menopausal
      transition.

PMID- 22997570
TI  - Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating
      in Female Rats.
AB  - Purpose. The present study evaluated the effect of Hypericum perforatum dry
      extract in an experimental model of binge eating (BE). Methods. BE for highly
      palatable food (HPF) was evoked in female rats by three 8-day cycles of food
      restriction/re-feeding and acute stress on the test day (day 25). Stress was
      induced by preventing access to HPF for 15 min, while rats were able to see and
      smell it. Hypericum perforatum dry extract was given by gavage. Results. Only
      rats exposed to both food restrictions and stress exhibited BE. The doses of 250
      and 500 mg/kg of Hypericum perforatum extract significantly reduced the BE
      episode, while 125 mg/kg was ineffective. The same doses did not affect HPF
      intake in the absence of BE. The dose of 250 mg/kg did not significantly modify
      stress-induced increase in serum corticosterone levels, suggesting that the
      effect on BE is not due to suppression of the stress response The combined
      administration of 125 mg/kg of Hypericum perforatum together with Salidroside,
      active principle of Rhodiola rosea, produced a synergic effect on BE.
      Conclusions. The present results indicate for the first time that Hypericum
      perforatum extracts may have therapeutic properties in bingeing-related eating
      disorders.

PMID- 22997571
TI  - Assessing Nutrient Intake and Nutrient Status of HIV Seropositive Patients
      Attending Clinic at Chulaimbo Sub-District Hospital, Kenya.
AB  - Background. Nutritional status is an important determinant of HIV outcomes.
      Objective. To assess the nutrient intake and nutrient status of HIV seropositive
      patients attending an AIDS outpatient clinic, to improve the nutritional
      management of HIV-infected patients. Design. Prospective cohort study. Setting.
      Comprehensive care clinic in Chulaimbo Sub-District Hospital, Kenya. Subjects.
      497 HIV sero-positive adults attending the clinic. Main Outcome Measures.
      Evaluation of nutrient intake using 24-hour recall, food frequency checklist, and
      nutrient status using biochemical assessment indicators (haemoglobin, creatinine,
      serum glutamate pyruvate (SGPT) and mean corpuscular volume (MCV)). Results.
      Among the 497 patients recruited (M : F sex ratio: 1.4, mean age: 39 years +/-
      10.5 y), Generally there was inadequate nutrient intake reported among the HIV
      patients, except iron (10.49 +/- 3.49 mg). All the biochemical assessment
      indicators were within normal range except for haemoglobin 11.2 g/dL (11.4 +/-
      2.60 male and 11.2 +/- 4.25 female). Conclusions. Given its high frequency,
      malnutrition should be prevented, detected, monitored, and treated from the early
      stages of HIV infection among patients attending AIDS clinics in order to improve
      survival and quality of life.

PMID- 22997572
TI  - Safety and Efficacy of Intravenous Ferric Carboxymaltose (750 mg) in the
      Treatment of Iron Deficiency Anemia: Two Randomized, Controlled Trials.
AB  - Background. Iron deficiency anemia (IDA) is a common hematological complication
      with potentially serious clinical consequences that may require intravenous iron
      therapy. Ferric carboxymaltose (FCM) is a stable, nondextran iron formulation
      administered intravenously in large single doses to treat IDA. Objective. Two
      open-label, randomized, placebo-controlled trials evaluated safety of multiple or
      single 750 mg FCM doses compared to standard medical care (SMC) in IDA patients.
      Secondary endpoints were improvements in hemoglobin and iron indices. Design and
      Patients. Adults with hemoglobin <=12 g/dL, ferritin <=100 or <=300 ng/mL with
      transferrin saturation <=30% were randomized to receive single (n = 366) or
      weekly (n = 343) FCM or SMC (n = 360 and n = 366). Results. Significantly greater
      (P <= 0.001) increases in hemoglobin and iron indices occurred in FCM groups
      versus SMC. In the multidose study, up to two infusions of FCM were needed to
      reach target iron levels versus 3-5 of intravenous iron comparators. FCM and SMC
      groups had similar incidences and types of adverse events and serious adverse
      events. Transient hypophosphatemia not associated with adverse events or clinical
      sequelae occurred in the FCM groups. Conclusion. Intravenous FCM is safe, well
      tolerated, and associated with improvements in hemoglobin and iron indices
      comparable to SMC when administered in single doses of up to 750 mg at a rate of
      100 mg/min. Fewer FCM infusions were required to reach target iron levels
      compared to other intravenous iron preparations.

PMID- 22997574
TI  - Safety and observations in a pilot study of lenalidomide for treatment in autism.
AB  - Autism affects 1 : 88 children in the United States. Familial history of
      autoimmune disease, autoantibodies in the serum of mothers when there is more
      than one autistic offspring, and neuroglial response in CSF and brain tissue in
      autistic patients suggest an immunological variable may be associated with this
      condition. Lenalidomide has the potential to invoke changes in TNF-alpha with
      less toxicity than thalidomide. This pilot study evaluated lenalidomide at
      reduction of TNF-alpha and improvement of behavior and language in children with
      autism with elevated TNF-alpha. Subjects with elevated TNF-alpha were given 2.5
      mgs lenalidomide daily for 12-weeks. Pharmacodynamics and safety was evaluated.
      Changes in language and autistic behaviors after six and twelve weeks were
      measured. Although statistical significance was not achieved for most measures,
      there were trends toward improvement. After 6-weeks, mean receptive language
      increased: 60.67 +/- 12.06 to 65.00 +/- 15.10 (P = 0.11) and symptoms of autism
      decreased (40.75 +/- 5.96 versus 38.67 +/- 7.90, P = 0.068). After 12-weeks, CSF
      TNF-alpha declined 57% +/- 25% from 80.5 +/- 41.03 to 38.0 +/- 31.27 (P = 0.068).
      Serum TNF-alpha declined 57% (92.50 +/- 68.92 to 40.25 +/- 44.53 (P = 0.048).
      This study suggests that lenalidomide is tolerated as a treatment by children
      with autism and should be further studied as a potential agent for cytockine
      inflammation.

PMID- 22997573
TI  - Stroke prevention in atrial fibrillation: understanding the new oral
      anticoagulants dabigatran, rivaroxaban, and apixaban.
AB  - Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)-direct
      thrombin inhibitor, dabigatran, and direct activated factor X inhibitors,
      rivaroxaban, and apixaban-do not require routine INR monitoring. Compared to
      VKAs, they possess relatively rapid onset of action and short halflives, but vary
      in relative degrees of renal excretion as well as interaction with p-glycoprotein
      membrane transporters and liver cytochrome P450 metabolic enzymes. Recent
      completed phase III trials comparing NOACs with VKAs for stroke prevention in
      atrial fibrillation (AF)-the RE-LY, ROCKET AF, and ARISTOTLE trials-demonstrated
      at least noninferior efficacy, largely driven by significant reductions in
      haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were
      acceptable compared to VKAs. Of note, the NOACs caused significantly less
      intracranial haemorrhagic events compared to VKAs, the mechanisms of which are
      not completely clear. With convenient fixed-dose administration, the NOACs
      facilitate anticoagulant management in AF in the community, which has hitherto
      been grossly underutilised. Guidelines should evolve towards simplicity in
      anticipation of greater use of NOACs among primary care physicians. At the same
      time, the need for caution with their use in patients with severely impaired
      renal function should be emphasised.

PMID- 22997575
TI  - The role of health literacy and social networks in arthritis patients' health
      information-seeking behavior: a qualitative study.
AB  - Background. Patients engage in health information-seeking behaviour to maintain
      their wellbeing and to manage chronic diseases such as arthritis. Health literacy
      allows patients to understand available treatments and to critically appraise
      information they obtain from a wide range of sources. Aims. To explore how
      arthritis patients' health literacy affects engagement in arthritis-focused
      health information-seeking behaviour and the selection of sources of health
      information available through their informal social network. Methods. An
      exploratory, qualitative study consisting of one-on-one semi-structured
      interviews. Twenty participants with arthritis were recruited from community
      organizations. The interviews were designed to elicit participants' understanding
      about their arthritis and arthritis medication and to determine how the
      participants' health literacy informed selection of where they found information
      about their arthritis and pain medication. Results. Participants with low health
      literacy were less likely to be engaged with health information-seeking
      behaviour. Participants with intermediate health literacy were more likely to
      source arthritis-focused health information from newspapers, television, and
      within their informal social network. Those with high health literacy sourced
      information from the internet and specialist health sources and were providers of
      information within their informal social network. Conclusion. Health
      professionals need to be aware that levels of engagement in health information
      seeking behaviour and sources of arthritis-focused health information may be
      related to their patients' health literacy.

PMID- 22997576
TI  - Dermatologic Toxicities from Monoclonal Antibodies and Tyrosine Kinase Inhibitors
      against EGFR: Pathophysiology and Management.
AB  - Epidermal growth factor receptor (EGFR) inhibition has now been well established
      as an effective treatment for various cancers. The EGFR belongs to the ErbB
      family of tyrosine kinase receptors which regulate tumor cell differentiation,
      survival and proliferation. Activation of EGFR drives tumorigenesis in lung, head
      and neck, colorectal and pancreatic cancers. Irrespective of the type of cancer
      being treated and the mechanism by which tumor EGFR drives tumorigenesis, the
      major side effect of EGFR inhibition is a papulopustular (also described as
      maculopapular or acneiform) rash which occurs in about two thirds of treated
      patients. Interestingly, this rash has been commonly correlated with better
      clinical outcomes (objective tumor response and patient survival). The
      pathophysiology of dermatological toxicity from EGFR inhibitors is an important
      area of clinical research, and the proper management of the rash is essential to
      increase the therapeutic index from this class of drugs. In this paper, we review
      the dermatologic toxicities associated with EGFR inhibitors with an emphasis on
      its pathophysiology and clinical management.

PMID- 22997577
TI  - Characterization of the phosphoproteome in human bronchoalveolar lavage fluid.
AB  - Global-scale examination of protein phosphorylation in human biological fluids by
      phosphoproteomics approaches is an emerging area of research with potential for
      significant contributions towards discovery of novel biomarkers. In this pilot
      work, we analyzed the phosphoproteome in human bronchoalveolar lavage fluid (BAL)
      from nondiseased subjects. The main objectives were to assess the feasibility to
      probe phosphorylated proteins in human BAL and to obtain the initial catalog of
      BAL phosphoproteins, including protein identities and exact description of their
      phosphorylation sites. We used a gel-free bioanalytical workflow that included
      whole-proteome digestion of depleted BAL proteins, enrichment of phosphopeptides
      by immobilized metal ion affinity chromatography (IMAC), LC-MS/MS analyses with a
      linear ion trap mass spectrometer, and searches of a protein sequence database to
      generate a panel of BAL phosphoproteins and their sites of phosphorylation. Based
      on sequence-diagnostic MS/MS fragmentation patterns, we identified a collection
      of 36 phosphopeptides that contained 26 different phosphorylation sites. These
      phosphopeptides mapped to 21 phosphoproteins including, for example, vimentin,
      plastin-2, ferritin heavy chain, kininogen-1, and others. The characterized
      phosphoproteins have diverse characteristics in terms of cellular origin and
      biological function. To the best of our knowledge, results of this study
      represent the first description of the human BAL phosphoproteome.

PMID- 22997578
TI  - A Prevalence of Imprinted Genes within the Total Transcriptomes of Human Tissues
      and Cells.
AB  - Genomic imprinting is an epigenetic phenomenon that causes a differential
      expression of paternally and maternally inherited alleles of a subset of genes
      (the so-called imprinted genes). Imprinted genes are distributed throughout the
      genome and it is predicted that about 1% of the human genes may be imprinted. It
      is recognized that the allelic expression of imprinted genes varies between
      tissues and developmental stages. The current study represents the first attempt
      to estimate a prevalence of imprinted genes within the total human transcriptome.
      In silico analysis of the normalized expression profiles of a comprehensive panel
      of 173 established and candidate human imprinted genes was performed, in 492
      publicly available SAGE libraries. The latter represent human cell and tissue
      samples in a variety of physiological and pathological conditions. Variations in
      the prevalence of imprinted genes within the total transcriptomes (ranging from
      0.08% to 4.36%) and expression profiles of the individual imprinted genes are
      assessed. This paper thus provides a useful reference on the size of the
      imprinted transcriptome and expression of the individual imprinted genes.

PMID- 22997579
TI  - Sedentary behavior and physical activity are independent predictors of successful
      aging in middle-aged and older adults.
AB  - Background. Sedentary behavior is emerging as an important risk factor for poor
      health. Physical activity has proven to be important in determining overall
      successful aging (SA) among older adults; however, no data exists on the
      influence of sedentary behavior on SA. The purpose of this analysis was to
      determine whether there is an association between sedentary behavior and
      successful aging, independent of physical activity levels. Methods. 9,478 older
      (M = 4,245; F = 5,233) and 10,060 middle-aged (M = 4.621; F = 5,439) adults from
      the Healthy Aging cycle of the Canadian Community Health Survey were analyzed.
      Multivariate logistic regressions were conducted with SA and its three components
      as outcomes while physical activity and sedentary behavior were entered as main
      exposures. Results. Among older adults, compared to those who were sedentary (4
      hours or more/day), those who were moderately (2-4 hours/day) and least sedentary
      (<2 hours/day) were 38% (OR: 1.38; CI: 1.12-1.69) and 43% (OR: 1.43; CI: 1.23
      1.67) more likely to age successfully, respectively. Among middle-aged adults,
      those who were least sedentary were 43% (OR: 1.43; CI: 1.25-1.63) more likely to
      age successfully. Conclusions. These novel findings suggest that sedentary
      activities are significantly associated with lower odds of SA among middle-aged
      and older adults, potentially in a dose-dependent manner.

PMID- 22997580
TI  - Learning from "Knocks in Life": Food Insecurity among Low-Income Lone Senior
      Women.
AB  - Building on earlier quantitative work where we showed that lone senior households
      reliant on public pensions in Nova Scotia (NS), Canada lacked the necessary funds
      for a basic nutritious diet, here we present findings from a qualitative study
      involving in-depth interviews with eight low-income lone senior women living in
      an urban area of NS. Using a phenomenological inquiry approach, in-depth
      interviews were used to explore lone senior women's experiences accessing food
      with limited financial resources. Drawing upon Bronfenbrenner's Ecological
      Systems Theory, we explored their perceived ability to access a nutritionally
      adequate and personally acceptable diet, and the barriers and enablers to do so;
      as well in light of our previous quantitative research, we explored their
      perceptions related to adequacy of income, essential expenses, and their
      strategies to manage personal finances. Seven key themes emerged: world view,
      income adequacy, transportation, health/health problems, community program use,
      availability of family and friends, and personal food management strategies.
      World view exerted the largest influence on seniors' personal perception of food
      security status. The implications of the findings and policy recommendations to
      reduce the nutritional health inequities among this vulnerable subset of the
      senior population are considered.

PMID- 22997581
TI  - Targeting anabolic impairment in response to resistance exercise in older adults
      with mobility impairments: potential mechanisms and rehabilitation approaches.
AB  - Muscle atrophy is associated with healthy aging (i.e., sarcopenia) and may be
      compounded by comorbidities, injury, surgery, illness, and physical inactivity.
      While a bout of resistance exercise increases protein synthesis rates in healthy
      young skeletal muscle, the effectiveness of resistance exercise to mount a
      protein synthetic response is less pronounced in older adults. Improving anabolic
      sensitivity to resistance exercise, thereby enhancing physical function, is most
      critical in needy older adults with clinical conditions that render them "low
      responders". In this paper, we discuss potential mechanisms contributing to
      anabolic impairment to resistance exercise and highlight the need to improve
      anabolic responsiveness in low responders. This is followed with evidence
      suggesting that the recovery period of resistance exercise provides an
      opportunity to amplify the exercise-induced anabolic response using
      protein/essential amino acid ingestion. This anabolic strategy, if repeated
      chronically, may improve lean muscle gains, decrease time to recovery of function
      during periods of rehabilitation, and overall, maintain/improve physical
      independence and reduce mortality rates in older adults.

PMID- 22997582
TI  - Association of social engagement with brain volumes assessed by structural MRI.
AB  - We tested the hypothesis that social engagement is associated with larger brain
      volumes in a cohort study of 348 older male former lead manufacturing workers (n
      = 305) and population-based controls (n = 43), age 48 to 82. Social engagement
      was measured using a summary scale derived from confirmatory factor analysis. The
      volumes of 20 regions of interest (ROIs), including total brain, total gray
      matter (GM), total white matter (WM), each of the four lobar GM and WM, and 9
      smaller structures were derived from T1-weighted structural magnetic resonance
      images. Linear regression models adjusted for age, education, race/ethnicity,
      intracranial volume, hypertension, diabetes, and control (versus lead worker)
      status. Higher social engagement was associated with larger total brain and GM
      volumes, specifically temporal and occipital GM, but was not associated with WM
      volumes except for corpus callosum. A voxel-wise analysis supported an
      association in temporal lobe GM. Using longitudinal data to discern temporal
      relations, change in ROI volumes over five years showed null associations with
      current social engagement. Findings are consistent with the hypothesis that
      social engagement preserves brain tissue, and not consistent with the alternate
      hypothesis that persons with smaller or shrinking volumes become less socially
      engaged, though this scenario cannot be ruled out.

PMID- 22997583
TI  - Placental amino acids transport in intrauterine growth restriction.
AB  - The placenta represents a key organ for fetal growth as it acts as an interface
      between mother and fetus, regulating the fetal-maternal exchange of nutrients,
      gases, and waste products. During pregnancy, amino acids represent one of the
      major nutrients for fetal life, and both maternal and fetal concentrations are
      significantly different in pregnancies with intrauterine growth restriction when
      compared to uncomplicated pregnancies. The transport of amino acids across the
      placenta is a complex process that includes the influx of neutral, anionic, and
      cationic amino acids across the microvilluos plasma membrane of the
      syncytiotrophoblast, the passage through the cytoplasm of the trophoblasts, and
      the transfer outside the trophoblasts across the basal membrane into the fetal
      circulation. In this paper, we review the transport mechanisms of amino acids
      across the placenta in normal pregnancies and in pregnancies complicated by
      intrauterine growth restriction.

PMID- 22997584
TI  - Smoking, cardiac symptoms, and an emergency care visit: a mixed methods
      exploration of cognitive and emotional reactions.
AB  - Emergency departments and hospitals are being urged to implement onsite
      interventions to promote smoking cessation, yet little is known about the
      theoretical underpinnings of behavior change after a healthcare visit. This
      observational pilot study evaluated three factors that may predict smoking
      cessation after an acute health emergency: perceived illness severity, event
      related emotions, and causal attribution. Fifty smokers who presented to a
      hospital because of suspected cardiac symptoms were interviewed, either in the
      emergency department (ED) or, for those who were admitted, on the cardiac
      inpatient units. Their data were analyzed using both qualitative and quantitative
      methodologies to capture the individual, first-hand experience and to evaluate
      trends over the illness chronology. Reported perceptions of the event during
      semistructured interview varied widely and related to the individual's intentions
      regarding smoking cessation. No significant differences were found between those
      interviewed in the ED versus the inpatient unit. Although the typical profile was
      characterized by a peak in perceived illness severity and negative emotions at
      the time the patient presented in the ED, considerable pattern variation
      occurred. Our results suggest that future studies of event-related perceptions
      and emotional reactions should consider using multi-item and multidimensional
      assessment methods rated serially over the event chronology.

PMID- 22997585
TI  - An individualized and everyday life approach to cognitive rehabilitation in
      schizophrenia: a case illustration.
AB  - Objective. The effectiveness of an individualized and everyday approach to
      cognitive rehabilitation for schizophrenia was examined in a case study. Method.
      After cognitive and functional assessment, concrete objectives were targeted for
      the person's everyday complaints. Strategies were constructed based on an
      analysis of the cognitive profile, daily life functioning, and processes involved
      in activities. They included a memory strategy for reading, a diary to compensate
      memory difficulties, and working memory exercises to improve immediate processing
      of information when reading and following conversations. Efficacy was assessed
      with outcome measures. Results. The program had beneficial effects on the
      person's cognitive and everyday functioning, which persisted at a 3-year follow
      up. Conclusion. Findings provide suggestive evidence that an individualized and
      everyday approach may be a useful alternative in order to obtain a meaningfully
      lasting transfer of training to daily life, compared to the nomothetic ones which
      dominate the field.

PMID- 22997586
TI  - Evaluation of manual and two-rotary niti retreatment systems in removing gutta
      percha obturated with two root canal sealers.
AB  - Objective. The objective of this study was to evaluate the efficacy of two
      retreatment NiTi systems (protaper universal retreatment files, R-Endo), when
      compared to manual technique in removing Gutta-percha obturated with two sealers.
      Study Design. Sixty extracted single-rooted premolars were instrumented with
      Protaper rotary files till F3. The specimens were divided into six groups. Groups
      1, 2, 3 were obturated with Gutta-percha and zinc oxide eugenol and Groups 4, 5,
      6 were obturated with Gutta-percha and AH-plus. The retreatment was carried out
      in groups 1 and 4 with H-files and GGdrills, groups 2 and 5 with R-endo
      retreatment files and groups 3 and 6 with Protaper retreatment files. The roots
      were sectioned and evaluated under optical stereomicroscope. Statistical analysis
      was performed with one-way ANOVA and Newman-Keul's test at P < 0.05. Results. The
      manual technique resulted in cleaner canal walls when compared with both rotary
      retreatment systems. Conclusion. NiTi rotary retreatment files can be used to
      remove the filling material quickly, but it should be followed by hand
      instruments to obtain better canal wall cleanliness.

PMID- 22997587
TI  - Necrotizing enterocolitis in very low birth weight infants: a systemic review.
AB  - Necrotizing enterocolitis (NEC) is the most common serious gastrointestinal
      disorder affecting very preterm or very low birth weight infants. The risk is
      inversely proportional to gestational age and weight at birth. Fetal growth
      restriction and compromise may be additional specific risk factors. Despite
      extensive research and animal studies etiopathogenesis, preventive strategies and
      management options remain controversial. The present paper reviews the literature
      for recent advances and newer insights for changing epidemiological trends,
      pathogenesis, role of inflammatory cytokines, and various preventive and
      management strategies.

PMID- 22997588
TI  - A high dose intravenous immunoglobulin therapy for women with four or more
      recurrent spontaneous abortions.
AB  - Recurrent spontaneous abortion (RSA) may have immunological etiology. The aim of
      this study was to assess the efficacy of a high dose intravenous immunoglobulin
      (HIVIg) therapy, in which 20 g of intact type immunoglobulin was infused daily
      for 5 days during early gestation, for women who had a history of four or more
      consecutive spontaneous abortions of unexplained etiology. A total of 60 pregnant
      RSA women underwent HIVIg therapy, and the pregnancy outcome was assessed. The
      live birth rate was 73.3% (44/60). Fifteen pregnancies ended in spontaneous
      abortion, and one ended in intrauterine fetal death. In 11 of the 15 spontaneous
      abortions, fetuses had abnormal chromosome karyotype. When the 11 pregnancies
      with abnormal chromosome karyotype were excluded, the live birth rate was as high
      as 89.8% (44/49). The HIVIg therapy may be effective for severe cases of
      unexplained RSA.

PMID- 22997589
TI  - Diagnostic value of exhaled carbon monoxide as an early marker of exacerbation in
      children with chronic lung diseases.
AB  - Chronic airways infection and inflammation are leading causes of morbidity and
      mortality in chronic lung diseases (CLD). Pulmonary exacerbations are major
      causes of morbidity in CLD. Exhaled carbon monoxide (eCO) is a product of
      endogenous metabolic processes whose presence in exhaled breath is considered an
      index of inflammatory processes. Objective. To evaluate carbon monoxide (eCO) as
      inflammatory marker for early detection of acute exacerbation in CLD. Methods.
      Case control study included 40 children with CLD (twenty in exacerbation, group I
      and twenty in quiescent period, group II) recruited from the Chest Clinic,
      Children's Hospital, Ain Shams University. Twenty apparently healthy children
      were included as controls (group III). Results. Patients' mean age was 9.98 +/-
      3.29 years: 24 (60%) males and 16 (40%) females. The mean eCO level among
      patients during exacerbation was 5.35 +/- 1.35 (ppm) compared to 2.65 +/- 0.49
      (ppm) in quiescent stage and 1.30 +/- 0.47 (ppm) in controls. eCO cutoff value
      discriminating cases and control was 1.5 (ppm) (sensitivity; 100% and specificity
      70%) and cutoff value discriminating group I from group II was 3 (ppm)
      (sensitivity: 100% and specificity: 100%). Conclusion. Exhaled CO can be
      considered a noninvasive early marker of acute exacerbation of CLD.

PMID- 22997592
TI  - Custom metal occlusal surface for acrylic resin denture teeth to enhance wear
      resistance: a case report.
AB  - Wear of the occlusal surface of the denture is a known fact which leads to
      subsequent changes in jaw relation, vertical dimension, loss of aesthetics, aged
      looks, and decrease in masticatory efficiency. Treatment modalities includes,
      change of denture set after a regular interval of 4-5 years, use of wear
      resistant denture teeth that includes wear resistant resin or porcelain teeth,
      teeth with cast metal occlusal surface, and altering occlusal contact areas of
      denture teeth by use of silver amalgam fillings. A case report of a patient who
      had increased tendency of occlusal wear was treated with custom made metal
      occlusal surface of denture teeth to enhance wear resistance and to improve the
      masticatory efficiency.

PMID- 22997590
TI  - CT Imaging of Coronary Stents: Past, Present, and Future.
AB  - Coronary stenting became a mainstay in coronary revascularization therapy.
      Despite tremendous advances in therapy, in-stent restenosis (ISR) remains a key
      problem after coronary stenting. Coronary CT angiography evolved as a valuable
      tool in the diagnostic workup of patients after coronary revascularization
      therapy. It has a negative predictive value in the range of 98% for ruling out
      significant ISR. As CT imaging of coronary stents depends on patient and stent
      characteristics, patient selection is crucial for success. Ideal candidates have
      stents with a diameter of 3 mm and more. Nevertheless, even with most recent CT
      scanners, about 8% of stents are not accessible mostly due to blooming or motion
      artifacts. While the diagnosis of ISR is currently based on the visual assessment
      of the stent lumen, functional information on the hemodynamic significance of in
      stent stenosis became available with the most recent generation of dual source CT
      scanners. This paper provides a comprehensive overview on previous developments,
      current techniques, and clinical evidence for cardiac CT in patients with
      coronary artery stents.

PMID- 22997591
TI  - Recurrent syncope in patients with carotid sinus hypersensitivity.
AB  - Syncope recurrence in pacemaker-implanted subjects for the cardio-inhibitory
      response to sinus carotid massage (SCM) was investigated. The study-hypothesis
      was that recurrences had significant vasodepressor responses that could justify
      the loss of consciousness. Forty-six patients were enrolled (16 patients and 30
      controls), followed and revaluated after 5-7 years. At the end of follow-up,
      significant differences were found between patients and controls in mean SCM SAP
      (87 versus 106 mmHg) and reduction in mean SCM SAP (59 versus 38 mmHg); in the
      number of symptomatic subjects soon after SCM (5 versus 1); and in the number of
      subjects suffering from orthostatic hypotension. A subgroup of 13 patients showed
      significantly different hypotensive responses to SCM compared with the values
      observed at study recruitment. The data showed that some subjects with a defined
      hemodynamic pattern in response to SCM may change their characteristics and have
      spontaneous and/or provocative symptoms. These data explain the syncopal
      relapses, and suggest the presence of autonomic dysregulation in individuals with
      carotid sinus hypersensitivity.

PMID- 22997593
TI  - Toxic haemorrhagic colitis: a rare presentation of eosinophilic colitis.
AB  - Eosinophilic colitis is a rare condition that usually presents with non specific
      abdominal symptoms. Very uncommonly it presents with an acute surgical emergency
      such as peritonitis or haemorrhage. We present a rare presentation of
      eosinophilic colitis with toxic hemorrhagic colitis and ischaemic bowel requiring
      laparotomy and bowel resection.

PMID- 22997594
TI  - Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive.
AB  - Mast cell leukemia (MCL) is a rare and aggressive disease with poor prognosis and
      short survival time. D816V c-KIT mutation is the most frequent molecular
      abnormality and plays a crucial role in the pathogenesis and development of the
      disease. Thus, comprehensive diagnostic investigations and molecular studies
      should be carefully carried out to facilitate the therapeutic choice. A MCL
      patient's case with rare phenotypic and genotypic characteristics is described
      with review of major clinical biological and therapeutic approaches in MCL.

PMID- 22997595
TI  - Spontaneous heterotopic pregnancy, simultaneous ovarian, and intrauterine: a case
      report.
AB  - Spontaneous heterotopic pregnancy is a rare clinical condition in which
      intrauterine and extrauterine pregnancies occur at the same time. The occurrence
      of an ovarian heterotopic pregnancy is a singular event as it comprises only 2.3%
      of all heterotopic pregnancies, extremely rare among women who conceive
      naturally. A case of a 28-year old patient was treated for spontaneously
      conceived heterotopic pregnancy. The patient was admitted to our center with
      lower abdominal pain and amenorrhoea. A transvaginal ultrasound scan showed an
      ovarian and an intrauterine heterotopic pregnancy. This was managed
      laparoscopically. Considering spontaneous pregnancies, every physician treating
      women of reproductive age should be aware of the possibility of heterotopic
      pregnancy. It can occur in the absence of any predisposing risk factors; only
      with an early diagnosis and treatment the intrauterine pregnancies will reach
      viability with a great chance of a favorable obstetric outcome.

PMID- 22997596
TI  - Primary renal lymphoma: long-term results of two patients treated with a
      chemotherapy + rituximab protocol.
AB  - Primary renal lymphoma (PRL) is a rare disease of which the etiology and
      pathogenesis remain controversial, and there is currently no standard treatment
      for it. We present the results of a long-term followup of two patients who were
      diagnosed with PRL and treated with cyclophosphamide, adriamycin, vincristine,
      prednisolone and rituximab (CHOP + R) regimen. Both patients reached a complete
      response, and there is no evidence of recurrence after 4.5- and 5-year followup
      periods. Based on our experience and other recently published studies, we
      recommend the combination of CHOP + rituximab as the elective treatment for this
      disease. To our knowledge, this is the longest followup period with a complete
      response that has been reported with this modality of treatment.

PMID- 22997597
TI  - Endometriosis of the terminal ileum: a diagnostic dilemma.
AB  - Endometriosis is characterized by the presence of endometrial tissue consisting
      of glands and/or stroma located outside the uterus. Involvement of the terminal
      ileum is extremely rare. Preoperative distinction of ileal endometriosis from
      other diseases of the ileocecal region is difficult in terms of clinical
      presentation, symptomatology, radiological appearance, and surgical and
      pathological findings. We report a case initially diagnosed as Crohn's disease
      due to a longstanding diarrhea with subsequent intestinal obstruction, but
      finally diagnosed as ileal endometriosis by histopathological evaluation after
      resection of the involved segment.

PMID- 22997598
TI  - Internet impact on the insertion of genitourinary tract foreign bodies in
      childhood.
AB  - Foreign body self-insertion into the urethra is an uncommon paraphilia. Variety
      in object form, motivation, clinical presentation, complications, and treatment
      options is a rule. In childhood it is very rare, and it is attributed to
      curiosity or mental disorders so far. However, the internet impact on daily life
      of all age groups has created a new category of sexual behavior in childhood and
      adolescence, the "internet induced paraphilia." Such is the case of an electrical
      cable inserted in the urethra of a 12-year-old boy reported here, which is
      representative of this kind of impact.

PMID- 22997599
TI  - Osteoid osteoma mimicking triangular fibrocartilage complex injury: diagnosis and
      review of treatment.
AB  - We report the case of osteoid osteoma (OO) with ulnar styloid involvement. A
      review of the literature has been made with the aim of defining the special
      behaviour of OO when it is near the articular surface. That behaviour can affect
      the diagnosis, masking the real etiology of the pain, delaying the diagnosis,
      missing the diagnosis, or what is more serious, conducting an inadequate
      treatment. We propose a treatment algorithm conducted based on the localization
      near or far from articular surface and the superficial or deep localization.

PMID- 22997600
TI  - Case of eosinophilic cystitis treated with suplatast tosilate as maintenance
      therapy.
AB  - Eosinophilic cystitis is a rare inflammatory lesion of the bladder, characterized
      by massive eosinophilic infiltration of the bladder wall. Its cause is not known
      definitely. A 49-year-old man consulted our department with a miction pain, gross
      hematuria, and frequent micturition. Urinalysis showed combined hematuria and
      pyuria, but urine culture was sterile. Abnormal findings of laboratory
      examination included an elevated white blood cell (WBC) count (15,700/MUL) and
      the proportion of eosinophils in the peripheral blood was 12% of the WBCs (normal
      0-5%). Cystoscopy revealed a solid mass with severe edematous mucosa. Magnetic
      resonance imaging (MRI) also indicated marked bladder wall thickening, which was
      suspected for invasive bladder cancer. Transurethral biopsy of the bladder mass
      was performed with pathological examination revealing features of eosinophilic
      cystitis. After administration of a combination of prednisolone and suplatast
      tosilate, followed by monotherapy with suplatast tosilate, regression of the
      bladder mass, and normalization of the count of peripheral eosinophils were
      achieved. Fourteen months after steroid therapy, under treatment with suplatast
      tosilate, there was no relapse of urinary symptoms and the bladder mass.

PMID- 22997601
TI  - The Impact of Experience with a Family Member with Alzheimer's Disease on Views
      about the Disease across Five Countries.
AB  - The objective of this paper is to understand how the public's beliefs in five
      countries may change as more families have direct experience with Alzheimer's
      disease. The data are derived from a questionnaire survey conducted by telephone
      (landline and cell) with 2678 randomly selected adults in France, Germany,
      Poland, Spain, and the United States. The paper analyzes the beliefs and
      anticipated behavior of those in each country who report having had a family
      member with Alzheimer's disease versus those who do not. In one or more
      countries, differences were found between the two groups in their concern about
      getting Alzheimer's disease, knowledge that the disease is fatal, awareness of
      certain symptoms, and support for increased public spending. The results suggest
      that as more people have experience with a family member who has Alzheimer's
      disease, the public will generally become more concerned about Alzheimer's
      disease and more likely to recognize that Alzheimer's disease is a fatal disease.
      The findings suggest that other beliefs may only be affected if there are future
      major educational campaigns about the disease. The publics in individual
      countries, with differing cultures and health systems, are likely to respond in
      different ways as more families have experience with Alzheimer's disease.

PMID- 22997602
TI  - Molecular events in primary and metastatic colorectal carcinoma: a review.
AB  - Colorectal cancer (CRC) is a heterogeneous disease, developing through a
      multipathway sequence of events guided by clonal selections. Pathways included in
      the development of CRC may be broadly categorized into (a) genomic instability,
      including chromosomal instability (CIN), microsatellite instability (MSI), and
      CpG island methylator phenotype (CIMP), (b) genomic mutations including
      suppression of tumour suppressor genes and activation of tumour oncogenes, (c)
      microRNA, and (d) epigenetic changes. As cancer becomes more advanced, invasion
      and metastases are facilitated through the epithelial-mesenchymal transition
      (EMT), with additional genetic alterations. Despite ongoing identification of
      genetic and epigenetic markers and the understanding of alternative pathways
      involved in the development and progression of this disease, CRC remains the
      second highest cause of malignancy-related mortality in Canada. The molecular
      events that underlie the tumorigenesis of primary and metastatic colorectal
      carcinoma are detailed in this manuscript.

PMID- 22997603
TI  - Evaluation of single column trapping/separation and chemiluminescence detection
      for measurement of methanethiol and dimethyl sulfide from pig production.
AB  - Reduced sulfur compounds are considered to be important odorants from pig
      production due to their low odor threshold values and low solubility in slurry.
      The objective of the present study was to investigate the use of a portable
      method with a single silica gel column for trapping/separation coupled with
      chemiluminescence detection (SCTS-CL) for measurement of methanethiol and
      dimethyl sulfide in sample air from pig production. Proton-transfer-reaction mass
      spectrometry (PTR-MS) was used to evaluate the trapping/separation. The silica
      gel column used for the SCTS-CL efficiently collected hydrogen sulfide,
      methanethiol and dimethyl sulfide. The measurement of methanethiol by SCTS-CL was
      clearly interfered by the high concentration of hydrogen sulfide found in pig
      production, and a removal of hydrogen sulfide was necessary to obtain reliable
      results. Air samples taken from a facility with growing-finishing pigs were
      analyzed by SCTS-CL, PTR-MS, and a gas chromatograph with sulfur
      chemiluminescence detection (GC-SCD) to evaluate the SCTS-CL. The difference
      between the concentrations of methanethiol and dimethyl sulfide measured with
      SCTS-CL, PTR-MS, and GC-SCD was below 10%. In conclusion, the SCTS-CL is a
      portable and low-cost alternative to the commercial methods that can be used to
      measure methanethiol and dimethyl sulfide in sample air from pig production.

PMID- 22997604
TI  - A Tetrahedral Representation of the Genetic Code Emphasizing Aspects of Symmetry.
AB  - The genetic code is a mapping of 64 codons to 22 actions, including polypeptide
      chain initiation, termination, and incorporation of the twenty amino acids. The
      standard tabular representation is useful for looking up which amino acid is
      encoded by a particular codon, but says little about functional relationships in
      the code. The possibility of making sense of the code rather than simply
      enumerating its codon-to-action pairings therefore is appealing, and many have
      attempted to find geometric representations of the code that illuminate its
      functional organization. Here, I show that a regular tetrahedron with each of its
      four faces divided into sixteen equilateral triangles (for a total of 64
      triangular 'cells') is a particularly apt geometry for representing the code. I
      apply five principles of symmetry and balance in order to assign codons to the
      triangular cells of the tetrahedral faces. These principles draw on various
      aspects of the genetic code and the twenty amino acids, making the final
      construct a positional balance of the amino acids and their functions rather than
      a re-analysis of them. The potential significance of this exercise, and others
      like it, is that this way of organizing the biological facts may provide new
      insights into them.

PMID- 22997605
TI  - [Application of multiple-locus variable number tandem repeat analysis (MLVA) on
      molecular typing of Leptospira interrogans].

PMID- 22997606
TI  - [Etiological study on viral diarrhea among children in Lulong, Hebei province].

PMID- 22997607
TI  - [Serotypes characterization and antimicrobial resistance on Shigella isolated
      from the Sui county during 2001-2008].

PMID- 22997608
TI  - [Typing and epidemiological analysis of human papillomavirus on female genital
      tract in Zhejiang province].

PMID- 22997609
TI  - [The optimal cutoff for screening mental disorders among the three scoring
      methods of the 12-item General Health Questionnaire].

PMID- 22997610
TI  - [Association between serum uric acid and prevalence of hypertriglyceridemia in
      middle and old aged people].

PMID- 22997611
TI  - [Intervention study on home-based eyesight health care among young pupils in
      cities].

PMID- 22997612
TI  - [Analysis of surveillance of iodine deficiency disorders between township and
      rural areas in Gansu province].

PMID- 22997613
TI  - Legal challenge against pilot badger cull fails.

PMID- 22997614
TI  - Support for a science-based, EU-wide animal welfare law.

PMID- 22997615
TI  - RVC becomes an FAO reference centre for veterinary epidemiology.

PMID- 22997616
TI  - Supporting better diagnosis of cattle diseases in sub-Saharan Africa.

PMID- 22997617
TI  - New test to tackle degenerative neurological disease in beagles.

PMID- 22997618
TI  - Reunion for the first Bristol graduates.

PMID- 22997619
TI  - DNA sequencing 'shaping the future of veterinary science'.

PMID- 22997620
TI  - Equine disease surveillance: quarterly summary.

PMID- 22997623
TI  - Removal notice to "Molecular mechanisms involved in resistance of CLL cells
      towards ABT-737, a specific BCL-2 inhibitor" [Toxicology 290 (December (2-3))
      (2011) 111].

PMID- 22997622
TI  - Assessing the quality of research needs to go beyond scoring: commentary on Crowe
      and Sheppard (2011). Authors' response.

PMID- 22997624
TI  - [Tuberculosis annual report 2010--(2) Tuberculosis in foreign nationals].
AB  - Surveillance data on tuberculosis (TB) in foreign nationals in Japan since 1998
      have been obtained. The proportion of foreign nationals infected with TB
      increased from 2.1% (739 patients) in 1998 to 4.2% (952 patients) in 2010. Most
      importantly, the proportion of TB patients aged 20-29 years among foreign
      nationals reached 29% in 2010. About half of the foreign nationals with TB were
      from China (29 %) and the Philippines (23%). In most cases, foreign nationals
      developed TB within 5 years of immigrating to Japan; moreover, 84% of these
      patients were 20-29 years old. The proportion of foreign nationals with TB among
      all TB cases was the highest in Hamamatsu city (9.5%), followed by Gunma
      prefecture, and Fukuoka city. Twenty-three percent of foreign nationals with TB
      were employed full-time, 22% were students, and 20% were unemployed. As the
      number of immigrants to Japan increases, the proportion of foreign nationals with
      TB is expected to increase, particularly among young adults and in those from
      countries with a high burden of TB.

PMID- 22997625
TI  - [Using of method and result of LUCC study in field of Chinese medicine
      resources].
AB  - The contradiction between the ecological environment, natural resources and the
      development of social and economic has become increasingly conspicuous. Land
      resources are the physical basis of Chinese medicine resources and habitat of the
      medicinal organisms. Meanwhile, land resources are also the bridge and tie
      between Chinese medicine resources and environment that include society and
      natural environment. Chinese medicine resources exist in the multiplexed system
      that constituted by the natural ecological environment and the human social
      environment. So the sustainable use of Chinese medicine resources includes the
      Chinese medicine resources itself and the nature environment and society
      environment that exist in. For the sustainable use of the Chinese medicine
      resources, it is necessary to study the change of Chinese medicine resources, the
      change of environment and the relationship between the Chinese medicine resources
      and environment that exist in. The technology method and result of land use and
      land cover change study, that can be use in the field of Chinese medicine
      resources change study. It can help researchers show the history, process,
      reason, and forecast the trend and result of Chinese medicine resources change.

PMID- 22997626
TI  - New questions about a popular heart procedure.  Research finds that angioplasty
      is used on those who may not need it.

PMID- 22997627
TI  - Gastroenteritis: more than just a stomach bug.

PMID- 22997628
TI  - Hernia repair: which surgical approach is best?

PMID- 22997629
TI  - Two keys to preventing falls.

PMID- 22997630
TI  - Asthma: not just for kids.

PMID- 22997631
TI  - I just started using a fentanyl patch for chronic back pain. What special
      precautions should I take?

PMID- 22997632
TI  - When I use my computer, I worry about carpal tunnel syndrome.  What can I do to
      prevent it?

PMID- 22997633
TI  - Troubles with sexual release? Don't be reluctant to discuss delayed or absent
      ejaculation with your doctor. The key to better sex is pinpointing the root
      cause.

PMID- 22997634
TI  - Heavy coffee drinkers live longer.

PMID- 22997635
TI  - Tele-counseling aids depression treatment.

PMID- 22997636
TI  - Flexible sigmoidoscopy: it works.

PMID- 22997637
TI  - Hawaii State Plan for Occupational Safety and Health. Final rule.
AB  - This document announces the Occupational Safety and Health Administration's
      (OSHA) decision to modify the Hawaii State Plan's ''final approval''
      determination under Section 18(e) of the Occupational Safety and Health Act (the
      Act) and to transition to ''initial approval'' status. OSHA is reinstating
      concurrent federal enforcement authority over occupational safety and health
      issues in the private sector, which have been solely covered by the Hawaii State
      Plan since 1984.

PMID- 22997638
TI  - Chromosomes of Tumor Cells. I. Murine Leukemias Induced by One or Two Injections
      of 7,12-Dimethylbenz[a]anthracene.

PMID- 22997639
TI  - Influenza A in a vaccinated population.

PMID- 22997641
TI  - [Aldo-keto reductase, AKR1B10].

PMID- 22997642
TI  - [Mechanism of central body temperature regulation by RANKL/RANK].

PMID- 22997643
TI  - [Mental health services in an urban setting: a crossroads of differences].

PMID- 22997644
TI  - [Difficulties and opportunities of psychiatric training in an urban setting: the
      example of Montreal].
AB  - In this article, the authors discuss the difficulties and opportunities of
      psychiatric training in an urban setting. Based on the example of Montreal, they
      ponder the interest and the relevance of this contextual framework for the
      training of future psychiatrists and other mental health professionals,
      regardless of the nature and location of their practice after their residency.
      The authors examine the advantages of this teaching environment and how to
      overcome its limits.

PMID- 22997645
TI  - [Young urban adults suffering from psychosis: the importance of close team work].
AB  - Untreated psychosis causes a lot of suffering and its impact echoes on different
      aspects of the affected individual's functioning. In city centers, youths
      presenting early psychosis face additional challenges because many of them live
      in precarious, unstable conditions and are isolated. Reorganisation of mental
      health care access and delivery is necessary to avoid delay for psychosis
      identification and treatment initiation. This article describes possible
      solutions which have been applied at Clinique JAP, a specialized early psychosis
      intervention clinic at the CHUM, which offers integrated services to optimize
      outcome. To increase engagement and adherence to treatment, treatment setting
      must include a welcoming and youth-friendly atmosphere, individualized and
      flexible interventions, and nourishing optimistic but realistic hope. Intensive
      interventions by a specialized interdisciplinary team, in collaboration with
      community organizations, must be offered in a proactive way to reduce delay in
      treatment and therefore avoid disastrous consequences of psychosis.

PMID- 22997646
TI  - [Close team work: sharing knowledge, solidarity and hope].
AB  - A proximity team was created more than eight years ago by a group of health
      professionals working with disaffiliated and homeless youth in the most
      precarious of situations. Proximity meetings have continued since that time,
      despite many changes within the team, including departures and new arrivals. The
      proximity team is a partnership project which revolves around common values and
      principles aimed at improving services for youth who find themselves marginalized
      or at risk of exclusion. Health professionals from various backgrounds explain
      why they believe in this approach to proximity work.

PMID- 22997647
TI  - [Integrated treatment of hepatitis C among people with concurrent mental health
      and substance abuse disorders: promoting change in an urban area].
AB  - In this article, the authors discuss the extent of HCV infections and the
      obstacles people with concurrent mental health and substance disorders face in
      terms of access to care in urban areas. The authors remind that HCV is associated
      with a reduced quality of life and an increased risk of cirrhosis, but that new
      treatments developed over the last decade can lead to the eradication of the
      virus and to the prevention of complications. The authors also describe the steps
      leading to the establishment of an HCV treatment program at the Centre
      hospitalier de l'Universite de Montreal (CHUM).

PMID- 22997648
TI  - [Vulnerability to environmental heat among persons with mental health problems].
AB  - This review is intended to alert health professionals to the particular
      vulnerability of persons with mental health problems or taking certain
      medications to heat-related illness, a threat that is increasing due to climate
      change. It reviews epidemiology, physiology and clinical features of heat-related
      illness. For acute medical management, it refers readers to existing guidelines
      and recommendations. It reviews risk and protective factors. Finally, it presents
      preventive strategies that may help reduce the impact of heat-related illness in
      this population.

PMID- 22997649
TI  - [Evaluation of inappropriate benzodiazepine use among the elderly: risk factors
      and impacts].
AB  - Inappropriate benzodiazepine use among the elderly is a common and frequently
      underestimated problem. The present literature revie explores benzodiazepine
      abuse in this population from a biological, psychological, and environmental
      perspective. A further objective is the identification of intervention strategies
      for addressing this problem. The scientific literature reveals a lack of
      consensus and validity concerning the description of BZD abuse. The prescription
      practices and somewhat lax attitudes of doctors working with the elderly
      contribute substantially to the lack of acknowledgement of the magnitude of this
      problem. Complications specific to the elderly, such as attitudes toward mental
      illness and differential manifestation of distress, are discussed. Difficulties
      related to the evaluation of anxiety and depression in elderly patients, have
      also been identified to contribute too many cases of BZD abuse. In conclusion, it
      is proposed that research in this area investigate integrative methods for
      evaluating BZD abuse in the elderly.

PMID- 22997650
TI  - [Insecure/disorganized attachment and borderline personality disorder: overcoming
      therapeutic problems].
AB  - In this article, the authors discuss the obstacles in the therapeutic
      relationship with patients with borderline personality disorder because of
      problematic transference. They present the case of a patient and describe a
      therapeutic impasse triggered by an exacerbated insecure/disorganized attachment.
      They discuss strategies to resolve the therapeutic deadlock elaborated according
      to the attachment theory formulation and the understanding of transference
      issues.

PMID- 22997651
TI  - [Links between personality disorders, attachment disorders and violent behavior:
      a literature review].
AB  - Past research has established that personality disorders and attachment disorders
      are important risk factors for the perpetration of violent acts in a context of
      an intimate relationship. Very few studies have been conducted linking
      personality and attachment disorders to violent behaviors outside of the domestic
      violence context. This paper proposes to address this gap by reviewing the
      literature and linking these important concepts to general violence. This will
      allow a better understanding of the dynamics of violence and possibly open the
      door to new research and interventions taking into account both attachment and
      personality disorders as prodromic factors.

PMID- 22997652
TI  - [Assimilation of problematic experiences: a case study on short-term dynamic
      psychotherapy].
AB  - The assimilation model is a qualitative and integrative approach that enables to
      study change processes that occur in psychotherapy. According to Stiles, this
      model conceives the individual's personality as constituent of different voices;
      the concept of voice is used to describe traces left by past experiences. During
      the psychotherapy, we can observe the progressive integration of the problematic
      voices into the patient's personality. We applied the assimilation model to a 34
      session-long case of an effective short-term dynamic psychotherapy. We've chosen
      eight sessions we transcribed and analyzed by establishing points of contact
      between the case and the theory. The results are presented and discussed in terms
      of the evolution of the main voices in the patient.

PMID- 22997653
TI  - Return to Joplin.

PMID- 22997660
TI  - Faith practices.

PMID- 22997662
TI  - Discipline.

PMID- 22997663
TI  - Old friends.

PMID- 22997664
TI  - More than a headache.

PMID- 22997665
TI  - Rethinking delivery models.

PMID- 22997666
TI  - Engulfed in an instant.

PMID- 22997667
TI  - No need for speed.
AB  - Confirmation by a nursing home resident's physician is frequently required prior
      to transport from the facility to a hospital. So in cases for which the need to
      transport isn't truly urgent but the assigned priority is lights and siren, EMS
      often rush to the scene only to wait while physician confirmation is obtained.
      With the protocol in place, routine response for non-urgent transport needs means
      that confirmation from the physician is often already being sought or has been
      received by the time the ambulance arrives. This theoretically places the crew
      "back in service" sooner. Reducing unnecessary lights-and-siren ambulance
      response in communities employing this type of response model can improve use of
      EMS resources. For example, some community-level EMS protocols in the Allina
      Health EMS service area have local police and fire dispatched to all medical 9-1
      1 calls. In non-emergent situations for which the protocol is now used, police
      and fire are no longer dispatched in situations they would previously have been
      dispatched concurrent with an unnecessary emergent response. The Allina Health
      Skilled Facility Ambulance Response Program provides an example of how EMS
      agencies can partner successfully with skilled-nursing facilities to promote the
      most appropriate use of ambulance services and effectively reduce the frequency
      of unnecessary emergent response. Limiting the use of lights-and-siren arrival to
      only those situations for which it's truly warranted improves safety and benefits
      nursing home residents by alleviating anxiety and disruption.

PMID- 22997668
TI  - Silent struggle.
AB  - The past 40-50 years of research and experience have given us improved knowledge
      of the pathophysiology and treatment of drowning injuries. Still, an all-too
      common event, the morbidity and mortality of drowning can be mitigated by
      prevention, recognition and target treatment. Old terms, such as "near drowning"
      and "secondary drowning," are confusing and misleading, and use of these terms
      should be abandoned. Most importantly, EMS personnel should understand that
      drowning is a hypoxic event resulting from submersion in a liquid. Most BLS and
      ALS strategies are designed to treat cardiac causes of respiratory and cardiac
      arrests (with recent change to a CAB algorithm). Drowning, however, is initially
      a purely hypoxic event and should be treated as such with ventilation and
      oxygenation (with an ABC algorithm). EMS and the fire service, because of their
      presence in the community, are uniquely positioned to play a major role in
      drowning prevention and treatment.

PMID- 22997669
TI  - Young'ns of EMS.

PMID- 22997670
TI  - [Continuing education in insurance medicine - a responsibility for reinsurers].

PMID- 22997671
TI  - [Longevity from the medical point of view--an increasing problem for life
      insurers].
AB  - Longevity is one of the most challenging processes for the developed societies in
      western countries. Social security systems and private insurance companies
      calculate their promises on the basis of demographic facts. The article will give
      an overview about the development of longevity in recent years, the most
      important studies and theories and the causes from a medical perspective.

PMID- 22997672
TI  - [Anxiety and anxiety disorders--differential diagnosis, etiology and medico-legal
      assessment (II)].

PMID- 22997673
TI  - [Magnetic resonance imaging criteria for the differentiation of traumatic and non
      traumatic rotator cuff tears].
AB  - It is often not easy to classify a rotator cuff tear into traumatic or non
      traumatic. For individual medical examinations the classification depends
      basically on the following four criteria: Case history, analysis of the accident,
      analysis of the complaints after the accident (or even before) and the
      pathomorphological findings. The aim of this study was to identify findings in
      the magnetic resonance imaging of the shoulder joints of patients with rotator
      cuff tears that could help in the differentiation of traumatic versus non
      traumatic. As a result it could be shown that infraspinatus and subscapularis
      tears, Hill-Sachs lesions and fractures of the tuberculum majus are significantly
      more detectable among those patients reporting a trauma. In contrast degeneration
      of the supraspinatus tendon, calcific tendinitis of the supraspinatus tendon, ac
      joint degeneration and an absence of the subacromial fat pad are more verifiable
      in the non-traumatic group. These results can be used as additional important
      information in the individual medical examination of patients with rotator cuff
      tears.

PMID- 22997674
TI  - [Psychiatric polypharmacy: hazard through drug-drug-interaction and possibilities
      for prevention].
AB  - Psychiatric diseases and comorbidity have increased over the past years. Commonly
      used psychotropic drugs contain a high risk of drug interactions and adverse drug
      events (ADE). With a frequency of 10-12% psychotropic drugs are, among all
      pharmaceuticals, the most common cause of hospitalisation due to ADE. During a
      hospital stay the application of psychotropic drugs can also lead to adverse drug
      events--sometimes due to drug interactions. Currently, ADEs and drug interactions
      are the most frequent cause of death for in-patients (18% of all causes of death)
      with an overall mortality of 0.95%. As studies have shown, hospitals as well as
      insurers could save a considerable amount of resources by implementing a system
      with on-ward pharmacists, hereby reducing ADE and re-hospitalisation rates. In
      recent studies a large amount of current ADEs were rated as preventable. Patient
      impairment due to ADE is leading to an increase in liability cases with an
      expected 5% increase of compensation payments in 2011. To evaluate these ADE
      related cases, a pharmaceutical assessment should be included in the expert
      trials, especially since a lack of awareness of medication errors is prevalent.
      When aiming towards a successful drug therapy, physicians must also consider that
      cheaper substances may often have an unfavourable drug interaction profile.

PMID- 22997675
TI  - [Self-affirmation in the workplace].
AB  - Self-affirmation establishes the basis for self-esteem through self-realisation
      in daily life and at the workplace. Examples of attainment of self-affirmation
      support motivation during adolescence where a lack of orientation in life causes
      socialisation to be at risk. Personal ambition to achieve superiority may provoke
      critical trends when assuming morally questionable behaviour at the workplace.
      Beginners in employment often face an atmosphere of unbalanced tension at work
      and deserve protective understanding and experienced support when striving for
      self-affirmation.

PMID- 22997676
TI  - ["Education" in an age of increasing equality--a path towards "ochlocracy"?
      (III)].

PMID- 22997677
TI  - [Modern developments in traditional Chinese medicine (TCM). Observations on the
      2012 43rd TCM Congress].

PMID- 22997678
TI  - [Of teeth, worms and legal liability].

PMID- 22997680
TI  - More states permit CRNAs to administer anesthesia without supervision. Colorado
      Medical Society v. Hickenlooper, 2011 COA 121, 11CA1005 COACA (7/19/2011)-CO.

PMID- 22997681
TI  - Nurse told patient of "incident" during surgery: all others remained silent! Case
      on point: Smith v. Hines, 2011 OK 51, 107198_P. 3d_(6/8/2012)-OK.

PMID- 22997679
TI  - [How many acupuncture treatments are medically necessary?].

PMID- 22997682
TI  - CA: Catheter accidently pulled: injury resulted: judgment for hospital reversed
      on appeal. Harry v. South Coast Medical Center, GO44770 CAAPP4-3 (5/11/2012)-CA.

PMID- 22997683
TI  - KS: Infiltration of IV sites: injuries resulted: judgment for hospital affirmed
      on appeal. Denning v. Lifepoint Hospitals, Inc., 277 P. 3d 1193 (6 /8/2012)-KN.

PMID- 22997684
TI  - Suit alleging RNs & MDs responsible for brain injury to newborn dismissed. Case
      on point: C.A. v. Bentolila, A-1261-11T1 NJSUP (8/9/2012)-NJ.

PMID- 22997685
TI  - Biological variation of hematology tests based on the 1999-2002 National Health
      and Nutrition Examination Survey.
AB  - OBJECTIVE: Biological variation consists of between-person (BP) and within-person
      (WP) variation. Estimates of WP coefficients of variation (CVw) and BP
      coefficients of variation (CVg) for hematology laboratory tests were estimated
      from the 1999-2002 National Health and Nutrition Examination Survey (NHANES).
      METHODS: NHANES is a survey of the civilian noninstitutionalized U.S. population
      that uses a stratified, multistage probability design. Between- and within-person
      variations were estimated for 18 hematology tests. For WP variation, a nonrandom
      sample was obtained with a median of 17 days between two test measurements.
      Between-person variation was estimated from the WP sample and additional
      participants were matched for age group, gender, and race and ethnicity to the WP
      sample. RESULTS: The BP and WP variations were estimated on as many as 2496 and
      852 sample participants, respectively. Mean corpuscular hemoglobin concentration
      had the lowest CVg (2.25% for men and 2.40% for women), and mean corpuscular
      volume had the lowest CVw (0.31% for men and 0.37% for women). The index of
      individuality (CVw/CVg) ranged from 0.06 for mean corpuscular volume for men and
      women to 0.62 for segmented neutrophil number for men, and 0.55 for segmented
      neutrophil percent for women. Women had higher CVw compared with men for
      hematocrit, hemoglobin, mean corpuscular volume, red blood cell count, and red
      blood cell distribution width. Several hematology tests' CVw also differed by age
      group, including mean corpuscular volume; eosinophil, lymphocyte and segmented
      neutrophil percent; monocyte and segmented neutrophil number; white blood cell
      count; and red blood cell distribution width.

PMID- 22997686
TI  - Editor's choice June 2012: scales for measuring everything.

PMID- 22997687
TI  - The importance of neglected tropical diseases in sustaining leprosy programmes.

PMID- 22997688
TI  - 'Double mainstreaming': including people affected by leprosy in poverty reduction
      programmes.

PMID- 22997689
TI  - An overview of training and development needs.

PMID- 22997690
TI  - Empowerment assessment tools in people with disabilities in developing countries.
      A systematic literature review.
AB  - INTRODUCTION: Many initiatives are undertaken to improve the empowerment of
      people with disabilities in developing countries. However, an overview of
      adequate measurement tools to evaluate such activities is not available to date.
      This systematic literature review aims to describe and assess the available tools
      to measure empowerment in people with disability, suitable for use in developing
      countries. METHODS: A systematic literature review was conducted. Articles were
      eligible when they described the development, validation, translation or the use
      of an instrument measuring empowerment in the context of disability. The
      instruments were assessed on their psychometric properties and on equivalence
      properties when they were translated. RESULTS: Thirty-six articles were found in
      which 17 questionnaires were developed, validated, translated or used. The
      questionnaires varied in the construct of empowerment, the target population and
      the psychometric properties. None of the questionnaires were developed or
      validated in a developing country. The psychometric properties and equivalence
      criteria were not adequately described and measured in any article. The
      Empowerment Scale (ES) of Rogers was the most often validated, translated and
      used questionnaire, receiving the highest number of positive ratings for the
      psychometric properties. DISCUSSION/CONCLUSION: The ES is the tool most widely
      used to measure empowerment, but adequate validation in a developing country
      context is still lacking. Cultural validity should be assessed in any culture
      before it is used. Further research is needed to develop empowerment instruments
      for developing countries and to assess the equivalence criteria, including
      psychometric properties of such questionnaires.

PMID- 22997691
TI  - A comparison of the change in clinical severity scale score and a retrospective
      physician assessment of neurological outcome in individuals with leprosy
      associated nerve function impairment after treatment with corticosteroids.
AB  - OBJECTIVES: To determine whether the measured change in score of a validated
      clinical severity scale reflected physician assessed improvement in individuals
      who had received corticosteroid therapy for leprosy associated nerve damage.
      DESIGN: Patients with nerve function impairment who participated in a randomised
      controlled trial of corticosteroids were classified into two groups using a
      retrospectively determined physician assessment of improvement. One group
      consisted of patients who had recovered or improved the other of patients who
      were unchanged or had deteriorated. The change in the clinical severity scale
      scores of these two groups was compared. RESULTS: The change in the clinical
      severity scale scores of the 34 eligible individuals in the two groups were
      significantly different (P = 0.003). Individuals in the group who recovered or
      improved had a greater change in severity score than those whose nerve function
      was unchanged or deteriorated. CONCLUSION: The scale for measuring the severity
      of leprosy Type 1 reactions (T1Rs) and/or nerve function impairment reflects the
      clinical improvement of individuals with leprosy associated nerve damage.

PMID- 22997692
TI  - Bacteriological results and leprosy reactions among MB leprosy patients treated
      with uniform multidrug therapy in China.
AB  - OBJECTIVES: To investigate the changes of bacteriological index and leprosy
      reactions among Multi-bacillary (MB) patients treated with uniform multi-drug
      therapy (UMDT). METHODS: Newly diagnosed leprosy patients were recruited after
      taking informed consent in three districts in Guizhou Province and one district
      in Yunnan Province China during November 2003 to June 2005 and were treated with
      Uniform Multidrug Therapy. All patients were followed up once a year for 3 years
      after completion of treatment. All data on bacteriological index (BI) and the
      frequencies of leprosy reaction were collected and analysed. RESULTS: A total of
      166 patients were recruited for UMDT trial. Among them 114 patients had positive
      BI smear, and 83 patients had been followed up for 42 months. The mean BI of 83
      patients decreased from 2.84 before treatment to 0.33 at the end of 42 months
      follow-up. At the end of this period, 61 patients (73.5%) had become BI negative.
      There were 13 (14.6%) patients who had a Type I reaction during 24 months of
      follow-up. One patient in the study group relapsed 13 months after stopping
      treatment of the UMDT. CONCLUSION: There was a significant decrease in the mean
      BI and 73.5% of patients treated with UMDT became BI negative during 3 years'
      follow-up. The frequency of Type I reaction seemed a little higher among patients
      treated with UMDT, but the numbers of patients enrolled were too few to determine
      statistical significance. Future studies on U-MDT should also study Type I
      reactions in these patients.

PMID- 22997693
TI  - Limitations in activities of people affected by leprosy after completing
      multidrug therapy: application of the SALSA scale.
AB  - OBJECTIVES: To identify people affected by leprosy with impairments after
      completing multidrug therapy for leprosy, and to assess their limitations in
      conducting daily activities by applying the Screening of Activity Limitation and
      Safety Awareness (SALSA) scale. METHODS: A cross-sectional study was performed of
      all residents of a medium-sized city who were treated for leprosy from 1998 to
      2006. A specific questionnaire was applied to obtain general and clinical data
      and the SALSA scale was used to assess limitations in activities. Impairments
      were assessed using the 'World Health Organization leprosy disability grading
      system' (WHO-DG). FINDINGS: Of the 335 people affected by leprosy treated in the
      period, 223 (62.1%) were located and interviewed. A total of 51.6% were female
      with a mean age of 54 years (SD +/- 15.72) and 67.9% had up to 6 years formal
      education. The borderline form predominated among interviewees (39.9%) and 54.3%
      suffer from associated diseases with hypertension (29.1%) and diabetes (10.3%)
      being the most common. Pain was reported by 54.7% of interviewees. By multiple
      logistic regression analysis, associations were found between limitations in
      activities and being female (P < 0.025), family income < or = 3 minimum wages (P
      value < 0.003), reports of major lesions (P-value < 0.004), pain (P-value <
      0.001), associated diseases (P-value < 0.023) and the WHO-DG (P-value < 0.001).
      Disabilities, as identified using the WHO-DG, were less common (32%) than
      limitations in activities as evaluated by the SALSA scale (57.8%). CONCLUSION:
      Limitations in activities proved to be common in people affected by leprosy and
      were associated with low income, being female, reported major lesions,
      disability, disease and pain.

PMID- 22997694
TI  - Patterns and trends of leprosy in Mexico: 1989-2009.
AB  - Data from the Mexican national leprosy control programme 1989-2009 are described
      and analysed. After initial increases associated with the introduction of MDT and
      the start of the global elimination initiative in the early 1990 s, both
      prevalence and incidence declined dramatically throughout most of the country.
      Reported prevalence fell below 1 per 10000 in 1994 and has remained below that
      level ever since. There is considerable geographic heterogeneity, with highest
      case detection rates in western states bordering the Pacific and lowest in the
      south east. Reasons for these geographic differences are unclear. There is
      evidence of increases in average age of cases, and in proportions male and MB, as
      in several other populations with declining leprosy. There is some evidence of
      increasing leprosy in states bordering on Texas, USA, where M. leprae is known to
      be harboured in armadillos. The relevance of armadillos for leprosy in Mexico is
      unclear but a priority question.

PMID- 22997695
TI  - Prevalence and characteristics of neuropathic pain in the people affected by
      leprosy in China.
AB  - OBJECTIVES: To determine the prevalence and the characteristics of neuropathic
      pain among the people affected by leprosy in China. METHODS: People affected by
      leprosy in four leprosy villages were interviewed about neuropathic pain with an
      interviewer-administrated questionnaire. RESULTS: In a total of 275 patients with
      leprosy interviewed, 126 (45.8%) reported having symptoms suggestive of
      neuropathic pain. The pain was severe in 70 (55.5%) patients, moderate in 49
      (38.9%) and mild in 7 (5.6%). Of the 126 patients with leprosy, 109 (86.5%)
      stated that the pain had some impact on their daily life: mild in 13 (10.3%),
      moderate in 45 (35.7%) and severe in 51 (40.5%). Sleep disturbance caused by pain
      was reported in 119 (94.4%) patients with leprosy: mild in 13 (10.3%), moderate
      in 51 (40.5%) and severe in 55 (43.6%). Ninety-six patients with leprosy (76.2%)
      reported that they had tried analgesics alone or in combination with steroids for
      the relief of their pain, of which 78 (81.2%) people reported that the treatment
      was effective. CONCLUSIONS: Neuropathic pain is not uncommon in both MB and PB
      patients who have completed effective antimicrobial treatment. The effectiveness
      of analgesics alone or in combination with steroids, in the treatment of
      neuropathic pain in patients with leprosy, needs to be studied.

PMID- 22997696
TI  - Borderline-lepromatous leprosy manifesting as granulomatous mastitis.
AB  - Leprosy is characterised by a chronic granulomatous inflammation of the skin and
      peripheral nerves. Dissemination of the lepra bacilli may cause involvement of
      other tissues as well. We describe an unusual case of the granulomatous
      involvement of the nipple-areola complex in a 35-year-old male consequent to
      borderline-lepromatous leprosy.

PMID- 22997697
TI  - The prevention of leprosy related disability as an integral component of the
      government health delivery programme in Myanmar.
AB  - This paper presents a record of a focus group discussion that took place in
      Nyapyitaw, Myanmar in December 2010. Those contributing to the focus group
      discussion were senior post holders in the National Leprosy Control Programme
      (NLCP), Myanmar. The Myanmar programme had been targeted for further enquiry
      after it became apparent, through an earlier survey of national programme
      managers and consultants, that the programme had been relatively successful in
      the measures taken to facilitate the integration of POD into the government
      health delivery programme. The experience gained by the NLCP, Myanmar was
      recorded and is offered here as an example of how POD can be successfully
      developed by a government leprosy control programme to become integral to general
      health delivery.

PMID- 22997698
TI  - [Eph family receptors as therapeutic targets].
AB  - Anti-angiogenic therapy is currently a commonly accepted and rapidly developing
      approach in oncology and other pathologies linked to aberrant neovascularization.
      Discovery and validation of additional molecular targets in angiogenesis is
      needed due to the limitations of the existing clinical therapeutics inhibiting
      activity of vascular endothelial growth factor (VEGF) and its receptors. A brief
      review of normal and pathological biological functions of the Eph family of
      receptor tyrosine kinases and their ephrin ligands is presented, and the
      approaches to developing therapeutics with anti- and pro-angiogenic and anti
      tumor activity based on selective molecular modulation of Eph-ephrin signaling
      pairs are discussed. Functional roles of Eph-kinases and ephrins in such
      mechanisms of cancerogenesis as cell proliferation and invasion are also
      addressed.

PMID- 22997699
TI  - [Design and synthesis of dipeptide mimetics of brain-derived neurotrophic
      factor].
AB  - Low-molecular mimetics of brain-derived neurotrophic factor (BDNF) loops 1 and 4
      representing to monomeric and dimeric amides of N-acyldipeptides were constructed
      and synthesized. The sequence of these dipeptides coinside with the central
      regions of beta-turns of corresponding loops of neurotrophine sequence, and acyl
      groups are bioisosters of preceding amino acid residues. Hexa- and
      heptamethylenediamine were used as spacers linking C-terminus ofdipeptides in
      BDNF dimeric mimetics. These substances were synthesized by classic peptide
      synthesis methods in solution and got laboratory codes GSB-104 (HO-Suc-Ser-Lys
      NH2), GSB-106 ([HO-Suc-Ser-Lys-NH-(CH2)3-]2), GSB-207 (HO-Suc-Met-Ser-NH2) and
      GSB-214 ([HO-Suc-Met-Ser-NH-(CH2)7/2-]2). By using the culture of immortalized
      hippocampal cell line HT-22 on the oxidative stress conditions it was shown that
      dimeric mimetics of both loops demonstrated neuroprotective activity in the
      concentration rage of 10(-5)-10(-8) M. Monomeric loop 1 mimetic GSB-207 was
      inactive in the same concentrations and monomeric loop 4 mimetic GSB-104 in a
      concentration of 10(-7) M decreased survival of neurons. Presence of
      neuroprotective activity only for dimeric mimetics correlates with the data that
      BDNF is active only in homodimeric form. As opposed to dimeric mimetic of loop 1
      GSB-214, dimeric mimetic of loop 4 GSB-106 demonstrates specific for BDNF
      antidepressive activity in Porsolt test on rats in doses 0.1 and 1 mg/kg i.p. It
      is suggested that antidepressive activity of BDNF is associated with its loop 4.
      We consider that compounds obtained will be useful for investigation of BDNF
      action mechanism and can lead to creation of a new group of medicinal substances
      with antidepressive and neuroprotective activities.

PMID- 22997700
TI  - [Synthesis of peptide fragments of high-affinity receptor FcepsilonR1 and study
      their binding with allergen-specific immunoglobulin E].
AB  - High-affinity receptor FcepsilonR1 is a key substance which participates in IgE
      dependent allergic reactions of immediate type. A minimal sequence Arg136-Asn137
      Trp138-Asp139, which takes part in binding with C3 and C4 fragments of IgE was
      determined by methods of computer analysis. As possible analogs of FcepsilonR1
      receptor, capable of binding to Fc-fragment IgE, a number of peptide compounds
      containing this sequence were proposed. Biological researches have shown that
      these peptides possess immunobiological effect and bind to IgE. Studied the
      ability of peptides to bind with IgE class serum antibodies specific to allergen
      Dermatophagoides pteronyssinus in patients with allergic bronchial asthma.

PMID- 22997701
TI  - [Influence of dioxane on the hydration shell of polypeptides].
AB  - Our interest in modifying influence of the low-molecular organic compounds on the
      hydration shell of biopolymers is due to a well-known fact that the former can
      act as regulators of the enzymatic activity changed the hydration shell of the
      latter. Dioxane was chosen because of its wide application in non-aqueous
      biocatalysis. In the present study we investigate the mechanisms of the dioxane
      influence on water of the first hydration layer of the model polypeptides by FTIR
      spectroscopy during simultaneous sorption of water-dioxane vapors into the
      polypeptide films at low water activity. It was found that modification of the
      hydration shell of the studied polypeptides was mainly due to the indirect
      ordering ofpolypeptide secondary structure at penetration of dioxane molecules at
      these conditions.

PMID- 22997703
TI  - [Bacteriolytic enzymes of blood plasma from sheep].
AB  - In the present work the studies ofbacteriolytic factors from sheep blood plasma
      have been performed. Three novel enzymes have been identified and characterized.
      Two of them have a molecular weight 15 +/- 2 kDa and able to lyse the gram
      negative Escherichia coli bacteria. The third enzyme has a molecular weight 34 +/
      4 kDa and is able to lyse both gram-negative Escherichia coli and gram-positive
      Micrococcus luteus bacteria. The bacteriolytic reactions have been studied for
      all three enzymes; particularly, pH-optima have been identified with respect to
      the substrate. To identify the enzymes trypsinolysis and consequent MALDI-TOF
      mass spectrometry studies were performed. The results were compared to data from
      publicly available databases, such as Swiss-Prot, NCBI, MSDB.

PMID- 22997704
TI  - [Proteases of calpain family in water invertebrates and fish].
AB  - The activity of Ca2+-dependent proteases, or calpains (EC 3.4.22.17), in a wide
      range of aquatic invertebrates (Oligochaeta, Hirudinea, Crustacea, Insecta,
      Gastropoda, Bivalvia) and vertebrates (Osteichthyes) was estimated. Detected
      molecular properties ofcalpains from the tissues of different species allow
      considering the complication of their structural organization and regulatory
      mechanisms between invertebrates and vertebrates in comparative-evolutionary
      aspect. Certain conclusions can be drawn about changes in the functional role of
      this proteolytic system in the cell metabolism.

PMID- 22997702
TI  - [Therapeutic effect of encapsulated into the nanocontainers MBP immunodominant
      peptides on EAE development in DA rats].
AB  - Multiple Sclerosis (MS) is a serve autoimmune neurodegenerative disease.
      Development of innovative approaches of MS treatment is of a high priority in the
      modern immunology and pharmacy. In the present study we showed high therapeutic
      efficiency of immunodominant peptides of myelin basic protein (MBP) incorporated
      into the monolayer mannosylated liposomes on the development of experimental
      autoimmune encephalomyelitis (EAE) in DA rats. MBP is a component
      ofoligodendrocytes' membrane, which form axonal sheath, and is one of the major
      autoantigens in MS. We analyzed binding pattern ofanti-MBP autoantibodies from MS
      patients using previously designed MBP epitope library. Utilizing the same
      approach we investigated pool of anti-MBP antibodies from SJL/J and C57/BL6 mice
      and DA rats with induced EAE. The most relevant rodent model to MS was EAE in DA
      rats according to the autoantibodies' binding pattern. We selected three
      immunodominant MBP fragments encapsulated in monolayer mannosylated liposomes for
      the following treatment of verified DA rodent model. MBP fragment 46-62 was the
      most effective in reducing of the first EAE attack, whereas MBP 124-139 and 147
      160 inhibited development of pathology during remission stage. Simultaneous
      administration of these peptides in liposomes significantly decreased level of
      anti-MBP antibodies. Synergetic therapeutic effect of MBP fragments reduced
      integral disease score by inhibiting first EAE wave and subsequent remission,
      thus, our findings disclosure novel approaches for efficient treatment of
      Multiple Sclerosis.

PMID- 22997705
TI  - [A novel endogeneous inhibitor from hepatopancreas of Kamchatka crab
      (Paralithodes camtschaticus)].
AB  - A novel endogeneous inhibitor from hepatopancreas of Kamchatka crab (Paralithosed
      camtschaticus) was isolatyed. The inhibitor was purifeid through fractional
      affinity chromatography on gramicidin-diasorb followed by gel-filtration at
      Sephadex G-100. The inhibitor PC is a protein (M, 66 kDa) and active against
      serine collagenolytic protease PC at temperature optimum 15-20 degrees C, stable
      at 4-40 degrees C and was completely inactivated after heating to 50 degrees C
      and higher. 0.9-20% NaCl is necessary for its inhibitor activity. The inhibitor
      was found to slow down cell spreading in vitro in cell type-dependent manner.
      Fibroblasts are most prone to inhibitory effect, epithelial tumor derived cells
      show medium susceptibility, while fibrosarcoma cells were not affected.

PMID- 22997706
TI  - [Bioluminescent reporters to identify gene allelic variants].
AB  - The method of single nucleotide polymorphism identification based on primer
      extension reaction (PEXT) with the following bioluminescent solid-phase
      microassay was developed. The recombinant Ca2+-regulated photoprotein obelin and
      coelenterazine-dependent luciferase Renilla muelleri were used as reporters.
      Factor V Leiden polymorphism 1691 G-->A (R506Q) of human F5 gene genotyping was
      used for investigation. Genomic DNA was amplified by PCR using primers, flanking
      polymorphic site of 140 base pairs. PCR products were used as a template for two
      PEXT reaction using two primers with 3'-end nucleotides, complementary either
      normal or mutant alleles. At complementarity of template and allelic-typical
      primer its extension with DNA-polymerase takes place. The products carried biotin
      due to availability ofbiotinylated dUTP in the reactions mixture. The assay was
      carried out using obelin-streptavidin chemical conjugates. Optimal PEXT-reaction
      conditions providing high reliability of SNP genotyping were found. A new
      approach to determine both alleles in one well was developed applying two
      bioluminescent reporters. Availability of the proposed approach was shown in the
      study of clinical DNA samples.

PMID- 22997707
TI  - [The functional analysis of polymorphic insertions of Alu retroelements at acute
      lymphoblastic leukemia].
AB  - Human genome variability observed within patient cohorts is considered as a goal
      of functional genomics essential for personalized medicine progress. In the
      current research we implement functional analysis of 31 polymorphic Alu
      insertions located within gene introns for individual genomes of patients with
      acute lymphoblastic leukemia (ALL). As a result we demonstrated a decrease of the
      primary transcripts content for 21 Alu-containing alleles. The most strong
      inhibitory effect of 10 Alu insertions was observed in both mononuclear blood
      cells of healthy donors and B-lymphoblasts of ALL patients. Allele frequencies of
      three Alu insertions that are located in MEF2C (two of them) and TAX1BP1 genes
      significantly differ (p-value 0.027. 0.052. 0.014 accordingly) between cohorts of
      healthy donors and ALL patients. Prolong influence of the Alu insertions on
      intracellular content of mature mRNA was studied for corresponding allele of
      TARBP1 gene.

PMID- 22997708
TI  - [Binding of human serum low-density lipoprotein cholesterol in vitro by sulfated
      pectin derivatives].
AB  - The ability to bind human serum LDL-C in vitro by the native pectins is lower
      than that of their sulfation derivatives. The number of sulfate groups and
      molecular weight of the sulfated derivatives are assumed to be crucial factors.
      The sulfated derivatives of pectin with molecular weight above 200 kDa containing
      45 wt % sulfate groups possess the highest ability to bind atherogenic lipids,
      the lowest activity was estimated for the derivatives with molecular weight below
      50 kDa containing 5 wt % of sulfate groups.

PMID- 22997709
TI  - Chemical investigation of Iphigenia stellata blatter by GC-MS.
AB  - GC-MS analysis of Iphigenia stellata Blatter in methanol extract revealed the
      presence of twenty chemical compounds in corm, nine in capsule wall, seven in
      leaves and six in seeds. Amongst the different phytochemicals identified 2-furan
      carboxaldehyde-5-(hydroxymethyl) (38% in corms), glycerine (35.4% in seeds) and n
      Hexadecanoic acid (31.5% in leaves, 28% in capsule wall) were significant.
      Iphigenia stellata is known for the presence of colchicine. However, in the
      methanol extract it was not detected.

PMID- 22997710
TI  - Study of skin anti-ageing and anti-inflammatory effects of dihydroquercetin,
      natural triterpenoids, and their synthetic derivatives.
AB  - Accessible triterpenoids of ursane and lupane series, the flavonoid
      dihydroquercetin and their synthetic derivatives with polar substituentss were
      tested in vitro for inhibition of collagenase 1 (MMP-1) in UVB irradiation assay.
      Ursolic acid and uvaol disuccinate were the most active inhibitors in the ursane
      series. In the lupane series, the best inhibition was manifested by carboxymethyl
      ester of betulonic acid and betulin succinates. Down- regulation of MMP-1 by
      dihydroquercetin and its synthetic derivatives surpassed the activity of a
      standard (retinoic acid).

PMID- 22997711
TI  - [Synthesis of structural fragments of natural flavonoids and flavolignans from 2'
      hydroxychalcones].
AB  - Structural analogues of natural flavonoids and flavolignans - new 2'-OAc
      chalcones and 2-hetaryl-3-aminochromons with the remnants of a 6-halogen-1,3
      benzodioxane, 1,4-benzodioxane and 1,5-benzodioxepan were synthesized. Structure
      of the obtained compounds was confirmed by the 1H NMR data.

PMID- 22997712
TI  - [Using of the luciferase reporter constructs for investigation of the capacity of
      Noggin2 protein to inhibit cell signaling pathways in early Xenopus laevis
      embryos].
AB  - Noggin (Noggin1) protein inhibits Smad1-dependent TGF-beta signaling pathway by
      extracellular binding of BMP proteins. Recently we found two previously unknown
      representatives of Noggin family - Noggin2 and Noggin4. Here we investigate by
      using the luciferase reporter constructs the ability of Noggin2 to inhibit BMP-,
      Activin/Nodal- and Wnt-signaling pathways in the early Xenopus laevis embryos.
      The effectiveness of this inhibitory activity of Noggin2 is comparing with that
      of well-known inhibitors of the indicated pathways - the secreted proteins
      Cerberus and Follistatin. Besides revealing of novel properties of Noggin2, our
      findings demonstrate that luciferase-reporter assay is as a useful tool for
      signaling pathways investigation in the model of Xenopus embryos.

PMID- 22997713
TI  - [Hepatitis E: current concepts].
AB  - Hepatitis E belongs to the group of enetral hepatites. Its earlier cases caused
      by genotype I and II viruses were reported largely from epidemics affecting
      tropical and subtropical countries. Sporadic cases of hepatitis E recorded later
      in West Europe, North America, Southeast Asia, and Oceania were caused by
      genotype III and IV viruses. Until recently the disease has been supposed to be
      reversible and have positive outcome barring women at late stages of pregnancy in
      whom cases of fulminate clinical course and death were described. This review
      focuses on recent publications devoted to hepatitis E in immunodeficient
      patients, such (as recipients of solid organ transplants, HIV-infected subjects
      and those treated with chemotherapy. Immunosuppression was shown to turn the
      disease into the chronic form or liver cirrhosis. Also, the infection has
      extrahepatic, mostly autoimmune complications. Current approaches to antiviral
      therapy and prevention of hepatitis E are discussed.

PMID- 22997714
TI  - [Small molecules--principal participants of pathogenesis of rheumatoid
      arthritis].
AB  - Poorly known pathogenetic mechanisms of rheumatoid arthritis (RA) including
      apoptosis and aging are considered with special reference to dysregulation of the
      p53 protein system. The main p53 regulators, p21 and PUMA proteins, as well as
      p53 antagonist, Mdm22 are described. The intensity of apoptosis varies throughout
      RA evolution from low to high at the early and late stages of the pathological
      process respectively. These variations are responsible for the hyperproliferative
      status of the synovial membrane. New PUMA-induced p53-independent mechanisms of
      apoptosis are described. Mdm2 may decrease activity of apoptosis of synovial
      cells. The role of aging in RA pathogenesis is due to impaired activity of p21
      associated with increased invasive potential of synovial cells. It is concluded
      that induction of apoptosis of synovial membrane cells may be a relevant
      therapeutic strategy for RA which implies the necessity of further studying the
      role of small molecules, viz. p53, p21 and PUMA, in its pathogenesis.

PMID- 22997715
TI  - [Peculiarities of present-day morbidity of influenza A (H1N1 swl)].
AB  - A rise in influenza morbidity became a topical problem again after the
      identification of a new H1N1 swl strain in California in 2009. In June 2009, WHO
      announced the onset of a new pandemic. We consider the epidemiological situation
      as regards respiratory viral diseases during recent years with special reference
      to influenza A (H1N1 swl). The literature data demonstrate the multifaceted
      clinical picture of this disease attributable to genetic variability of the virus
      and the immune response to infection. Most cases of influenza A (H1N1 swl) are
      either mild or severe diseases; it may be especially serious in previously
      unaffected young and middle-aged subjects and develop into acute respiratory
      distress syndrome with the fatal outcome. As a rule, the most severe cases are
      recorded in high-risk groups. Pathomorphological changes associated with pandemic
      influenza are described in comparison with those documented in earlier pandemics.

PMID- 22997716
TI  - [Comparative characteristic of the hormonal profile in men with stable
      obstructive pulmonary disease and smokers].
AB  - Comparative analysis of the hormonal profile was performed in 12 and 16 patients
      with mild and moderately severe chronic obstructive pulmonary disease (COPD)
      respectively, in 25 patients with chronic bronchitis, 13 smokers without
      respiratory symptoms and dysfunction of external respiration, and in healthy non
      smokers. Patients with moderately severe COPD had lower concentrations of total
      and free testosterone and DHEA than smokers with chronic bronchitis and mild
      COPD. Blood androsterone level positively correlated with the forced expiratory
      volume during the first second and inversely related to the duration of smoking
      and severity of coughing.

PMID- 22997717
TI  - [Comparing moderately late results of the application of stents coated with a
      medicinal antiproliferative agent for the treatment of patients with various
      forms of coronary heart disease: their efficacy and safety].
AB  - Extensive application of stents coated with a medicinal antiproliferative agent
      in clinical practice significantly improved late results of endovascular
      treatment of patients with various forms of coronary heart disease (CHD). The
      largest clinical experience is gained with the use of sirolimus- and paclitaxel
      coated stents (Cypher, J&J; Cordis, and Taxus, Boston Scientific). However recent
      publications suggest a rather high frequency of late thrombosis after
      implantation of such stents. The aim of this work was to estimate their efficacy
      and safety during the 6-8 month follow-up in 712 patients with various forms of
      CHD to whom 910 sirolimus- and paclitaxel-coated stents were implanted. The
      immediate positive angiographic result was documented in 98.8% of the cases in
      group 1 (n=514, 667 Cypher stents) and 96,7% in group 2 (n=198, 243 Taxus
      stents). Acute thrombosis was documented in 1 patient of each group (p > 0.5).
      The frequency of restenosis was 2.9 and 3.1% in groups 1 and 2 respectively (p >
      0.5). Late thrombosis within 1 year after implantation occurred in 0.4 and 1% of
      the patients respectively (p > 0.5). Late thrombosis is supposed to be due to a
      variety of factors, viz. withdrawal of antithrombotic therapy, incomplete stent
      opening, the use of non-absorbable polymer; suppression of epithelization, etc.
      All patients undergoing steent implantation are in need of antiaggregation
      therapy with acetylsalicylic acid and clopidogrel till the cause of late
      thrombosis is clarified.

PMID- 22997718
TI  - [Cardiac complications and heart rhythm variability in the late post-stroke
      period].
AB  - The aim of this prospective study was to elucidate the relationship between
      cardiac complications and heart rhythm variability (HRV) in 90 patients (age
      median 58 (53;67) years) with the sinus rhythm after ischemic stroke. 24-hr
      Holter monitoring 21 days after stroke was used for temporal and spectral
      analysis of HRV. The follow-up period lasted 23 (12; 45) months. Ten (11%)
      patients of this group developed acute myocardial infarction, unstable angina,
      acute cardiac failure or sudden cardiac death. The remaining 80 (89%) patients
      constituted group 2. The two groups were matched for the duration of prospective
      observation, sex, ischemic stroke subtype, the size and localization of brain
      infarction, multiplicity of focal cerebral lesions, severity of neurologic
      disorders (Rankin scale), the history of myocardial infarction, the presence of
      diabetes and chronic heart failure. Patients of group 1 were older in the end of
      the acute stroke period than those of group 2 (68 (61;72) and 57 (51;66) years)
      respectively. They, more frequently suffered CHD (stable angina) and had lower
      spectral characteristics of HRV (p < 0.05).

PMID- 22997719
TI  - [Management of arrhythmia in patients with arterial hypertension].
AB  - We estimated the risk of arrhythmic complications after the use of cardiovascular
      medications in a prospective study including 123 patients with arterial
      hypertension and recurrent atrial fibrillation. Dispersion characteristics of P
      wave and QT interval were studied in patients with left ventricular concentric
      remodeling, concentric hypertrophy, and eccentric hypertrophy. The role of
      therapy with beta-blockers. ACE inhibitors, and preductal in the reduction of the
      risk of atrial fibrillation and ventricular arrhythmia was evaluated.

PMID- 22997720
TI  - [Dynamics of microrheologic properties of erythrocytes in patients with arterial
      hypertension and dyslipidemia treated with atorvastatin].
AB  - The aim of this work was to study the influence of atorvastatin,
      hydroxymethylglutaryl coenzyme A reductase inhibitor, on microrheologic
      properties of erythrocytes in patients with arterial hypertension and
      dyslipidemia. 33 patients (mean age 52.8+-1.7 years) having grade I-II AH with
      type IIb dyslipidemia, risk 3 (DAGZ criteria. 2008) were compared with 26 age
      matched healthy subjects. Atorvastatin therapy optimized blood lipid spectrum,
      lipid peroxidation, and lipid composition of erythrocyte membranes within 16
      weeks after the onset. It decreased activated lipid peroxidation in erythrocytes
      due to enhanced antioxidant protection. The blood diskocyte level was normalized
      within 16 weeks of therapy. Simultaneously, the total number of reversibly and
      irreversibly altered erythrocytes decreased to the stable normal level. The total
      number and size of erythrocytes in an aggregate were also close to those in
      healthy subjects while the amount of unbound cells increased.

PMID- 22997721
TI  - [Predictors of cardiovascular and cerebral complications in patients with
      rheumatoid arthritis].
AB  - This 5-year long prospective cohort study of 124 young and middle-aged patients
      with rheumatoid arthritis (RA) initially without signs of cardiovascular diseases
      (CVD) aimed at estimating the risk and predictors of cardiovascular and
      cerebrovascular complications. The patients remained under observation till the
      following end-points were reached: coronary heart disease, chronic heart failure,
      disturbed cerebral circulation, cardiovascular death. The following predictors of
      unfavourable outcome were analysed: CVD risk factors, RA inflammatory activity,
      and markers of preclinical CVD. Ultrasonic scanning, dopplerography of common and
      internal carotid arteries, echocardiography, and determination of ankle-brachial
      index were used. 15 patients reached the end-points; specifically 6 cases of CVD,
      4 cerebrovascular complications, and 5 deaths were documented. The total
      proportion of those survived without CVD was 0.88 (an equivalent to 15 (12%) of
      the observed events). Survival time till the end-points was 2.41+-1.54 years. CRP
      level 24 mg/l or higher (odd ratio 3.09, 95% CI 1.03-9.29), smoking (odd ratio
      6.6, 95% CI 2.05-21.21), presence of atherosclerotic plaques (odd ratio 6.6, 95%
      CI 2.05-21.21) and calcinated plaques (odd ratio 8.95, 95% CI 1.36-47.03) in
      carotid arteries, SCORE risk >5% (odd ratio 19.82, 95% CI 3.25-41.75) were
      predictors of unfavourable prognosis in RA patients for the nearest 5 years.
      These data emphasize the necessity of thorough examination of RA patients for
      asymptotic atherosclerosis taking account of inflammatory activity and CVD risk
      factors for the optimization of early diagnostics and prediction of CVD.

PMID- 22997722
TI  - [Diagnostics and treatment of coronary heart disease and concomitant climacteric
      cardiopathy].
AB  - To improve differential diagnostics and treatment of coronary heart diseases
      (CHD) and concomitant climacteric cardiopathy (CCP), we analysed results of
      clinical examination and laboratory-instrumental studies of 1063 women
      complaining of chest pain. They were divided in 3 groups: group 1 (817 patients
      with CHD), group 2 (134 patients with CCP), group 3 (122 patients with CHD+CCP).
      Peculiarities of laboratory and instrumental diagnostics are described in
      conjunction with comparative characteristic of multispiral CT coronarography and
      corononaroangiography.

PMID- 22997723
TI  - [Effect of combined hormonal oral contraception on the somatic and psychic status
      of women of reproductive age].
AB  - The paper is devoted to the topical problem of maintaining somatic and psychic
      health of the women of reproductive age by rational pregnancy planning and
      prevention of abortions by modern methods of contraception including combined
      oral hormonal contraception. Unfortunately, this approach is rarely employed in
      this country (5-6%). Results of retrospective analysis of medical documentation,
      clinical efficacy and safety of modern combined oral hormonal contraception are
      presented.

PMID- 22997724
TI  - [Pathogenetic therapy of metabolic syndrome at the stage of visceral lesions].
AB  - Insulin resistance and oxidative stress play an important role in the
      pathogenetic mechanism of non-alcoholic fatty liver disease. Hepatoprotective
      therapy that blocks the second phase of pathogenesis (oxidative stress) is a
      promising modality for the treatment of non-alcoholic steatohepatitis (NACH). An
      alternative approach is the use of medicines recovering the mitochondrial
      membrane, lipid bi-layer of the plasma membrane, oxidative phosphorilation, and
      cellular metabolism. In this context, succinic acid-based remaxol showing
      antioxidative, antihypoxic and cytoprotective activities can be regarded as a
      promising metabolic hepatoprotector for the treatment of non-alcoholic fatty
      liver disease. The present original study demonstrated the clinical efficacy of
      remaxol in pathogenetic therapy of NACH in patients with metabolic syndrome. Its
      introduction in the combined treatment of NACH increased functional capacity of
      the liver by decreasing the severity of cytolysis, cholestasis, hepatomegalia,
      and steatosis (ultrasonic study), improved lipid metabolism, reduced cholesterol
      level, triglyceridemia, and atherogenic index. Remaxol exerted nephroprotective
      action in patients with diabetic nephropathy at stage 1 of chronic renal
      insufficiency (increased glomerular filtration rate and decreased blood
      creatinine level). The study demonstrated the advantage of medications with
      antihypoxic properties over traditional therapy of NACH.

PMID- 22997725
TI  - [Potentialities of medicinal correction of cerebrovascular disturbances in
      patients with arterial hypertension].
AB  - The use of up-to-date diagnostic methods for the examination of 72 patients
      presenting with grade II-III arterial hypertension and high risk of
      cardiovascular complications made it possible to estimate the state of
      brachiocephalic arteries before and after combined antihypertensive therapy that
      continued during 14 days. The following variables were measured: blood flow rate,
      peripheral vascular resistance indices at the extra- and intracranial levels,
      metabolic indices of cerebrovascular responsiveness, and coefficient of
      variability as an indicator of the cerebrovascular reserve capacity under
      conditions of antihypertensive treatment. Three antihypertensive therapeutic
      regimens were employed, viz. lisinopril plus indapamide, bisoprolol plus
      indapamide, and amlodipine plus indapamide. It was shown that all the three
      regimen resulted in positive changes in the parameters of blood flow and
      peripheral vascular resistance. At the same time, the use of amlodipine plus
      indapamide ensured a more gradual reduction of peripheral vascular resistance and
      the most pronounced increase of cerebrovascular reserve capacity compared with
      the two remaining regimens. It is concluded that the parameters of peripheral
      vascular resistance and metabolic indices of cerebrovascular responsiveness are
      the most sensitive and informative end points for the pharmacotherapeutic
      treatment of cerebral hemodynamics in the patients presenting with grade II-III
      arterial hypertension and high risk of development of cardiovascular
      complications.

PMID- 22997726
TI  - [Peculiarities of clinical and X-ray picture of pneumonia in patients with
      influenza A (H1N1)].
AB  - A distinctive feature of pneumonia in influenza A (H1N1) is interstitial
      infiltration of lung tissues and high frequency of pulmonary lesions leading to
      acute lung injury/acute respiratory distress syndrome in half of the patients.
      Severe clinical course of the disease and complications (pleuritis, abscess,
      pulmonary thromboembolism) diagnosed by X-ray were recorded in 29% of the
      patients. The final X-ray examination revealed normalization of the lung
      structure only in 15.5% of the cases mostly the patients with mild pneumonia.
      15.5% of them developed post-pneumonic changes in the form of diffuse
      pneumosclerosis, pleural adhesions, and dry cavities in the lung tissue.
      Pulmonary CT is believed to be the most informative method for diagnostics of
      pneumonia and its complications during influenza A (H1N1).

PMID- 22997727
TI  - [Lesions in the nervous system during chemotherapy of acute leukosis and non
      Hodgkin lymphomas].
AB  - We studied lesions in the nervous system of 60 patients with acute leukosis and
      25 with non-Hodgkin lymphomas during standard chemotherapy. Toxic encephalopathy
      was diagnosed in 6 (10%) patients with acute leucosis treated by endolumbal
      administration of metotherxate, cytarabine and prednisolone (to prevent
      neuroleukemia) and in 2 (8%) patients with non-Hodgkin lymphomas. 5 (8.3%)
      patients with acute leukosis and 5 (20%) with non-Hodgkin lymphomas suffered
      polyneuropathy after vincristine therapy. Acute disturbance of cerebral
      circulation was documented in 17 (28.3%) patients with acute leucosis.

PMID- 22997728
TI  - [Exploration of the region of Kavkazskie Mineral'nye Vody (Caucasian Mineral
      Waters) by the physician humanist F.P. Gaaz].

PMID- 22997729
TI  - [Trends of genome evolution in land and secondary-water herbs].
AB  - Comparative analysis of genome sizes in two groups of herbs, land and secondary
      water, has been released. It is shown that their genomes are changed to opposite
      topics in cenozoic. The genome of land herbs is increased, and it is decreased in
      secondary water herbs. Genome growth in land herbs is analyzed as the result of
      unfavourable changes in global climate: cooling, aridization and atmospheric CO2
      deficit. Genome minimization in secondary-water herbs is interpreted as the
      sequence of united effect of two groups of factors: returning to more stable
      water environment and breakdown of symbiotic relations with fungi partner. The
      influence of environmental discomfort and development of symbiotic or parasitic
      relations on genome size is discussed in association with established
      differences.

PMID- 22997730
TI  - [The functional state of biogenic amines- and acetylcholine-regulated signaling
      systems of the brain in diabetes mellitus].
AB  - The role of hormonal signaling systems in the etiology and pathogenesis of
      diabetes mellitus (DM) and the neurodegenerative diseases induced by them is
      currently poorly understood. It is generally accepted that the main causes of
      diabetes of types 1 and 2 and their CNS complications are disturbances in
      signaling systems regulated by insulin, leptin and glutamate. However, in recent
      years, there are many evidences in favor of participation of the brain signaling
      systems regulated by biogenic amines and cholinergic receptor agonists in the
      development of these diseases. The alterations in the expression and functional
      activity of signal proteins, the components of these systems, as well as the
      disturbances of the biosynthesis, transport and degradation of signal molecules
      for their regulation contribute significantly to the pathological processes in
      the brain in DM, and in some cases themselves are a trigger for the development
      of this disease. The main factors that cause dysfunctions of dopaminergic,
      serotonergic, adrenergic and cholinergic systems of the brain in DM are
      hyperglycemia and insulin resistance, and hypoglycemia that occurs as a result of
      inadequate insulin therapy. This review is devoted to the functional state of the
      brain signaling systems regulated by biogenic amines and cholinergic agonists in
      DM, as well as the relationship between the changes in these systems and the
      development of neurodegenerative processes in the diabetic brain.

PMID- 22997731
TI  - [Effect of GABA and glycine neuromediator interaction in the central nervous
      system].
AB  - Today it is well accepted that GABA can be co-localized and co-released with
      glycine in the same synapse. This article provides an overview of GABA and
      glycine co-localization and the effects of simultaneous activation of GABAA and
      glycine receptors. The review deals with mechanisms of direct and indirect
      receptor interaction, as well as with the effect of non-selective activation of
      glycine receptors by GABA.

PMID- 22997732
TI  - [Comparison of human endometrial stem cells and fibroblasts resistance to
      oxidative stress].
AB  - The response of human endometrial stem cells (hESCs) to oxidative stress has been
      investigated by flow cytometry. Two terminally differentiated cell lines were
      used for the comparison: human embryonic lung fibroblasts and human dermal
      fibroblasts. The oxidative stress was designed by hydrogen peroxide (H2O2) action
      in the wide range of concentrations (50-1500 microM) during 24 h. It has been
      shown that the H2O2 amount per one cell (pM/cell), but not H2O2 concentration in
      the growth medium, should be taken into account for the accurate evaluation of
      H2O2 effect on different cell lines. Therefore, in our experiments LD50 reflects
      the amount of H2O2 per cell, at which 50% cells survived after 24 h. We have
      demonstrated that hESCs are more resistant to H2O2 than embryonic lung
      fibroblasts, but less resistant than dermal fibroblasts.

PMID- 22997733
TI  - [The effect of hydroxyurea on the ciliogenesis in ciliated epithelium of mollusk
      Lymnaea stagnalis].
AB  - An active proliferation of the cells of ciliary epithelium in the foot of mollusk
      Lymnaea stagnalis was shown using radioautography. Cells labeled with 3H-tymidine
      were clustered into small groups. Hydroxyurea treatment decreased the
      proliferation of the epithelial cells. Scanning electron microscopy showed that
      surface of the mollusk foot was covered by extensive ciliated folds. The clusters
      of the cells covered with microvilli and with short cilia were localized at the
      bases of these folds. The cells covered with microvilli and with short cilia
      disappeared after 24 h of hydroxyurea treatment, ciliary epithelium appeared
      homogeneous and was composed of only multi-ciliated cells. Transmission electron
      microscopy showed no effect of the hydroxyurea on the centriole- and ciliogenesis
      in the multi-ciliated cells. We suggest that hydroxyurea inhibits cell
      proliferation and induces the differentiation of cells covered with microvilli in
      multi-ciliated cells.

PMID- 22997734
TI  - [Energy corrective and antioxidative actions of cytoflavin during postischemic
      period of human dermal fibroblasts in vitro].
AB  - The influence of metabolic drug Cytoflavin (CF) with antihypoxic and
      antioxidative properties on human dermal fibroblasts in a model of ischemia
      reoxygenation in vitro was studied. It was revealed that the restoration of ATP
      synthesis in fibroblasts in the postischemic period was considerably accelerated
      (in 2.1 times) by the addition of CF to the culture medium. The drug had a cell
      protective effect of reducing cell mortality during the reoxygenation after
      ischemia by 2-2.7 times. CF effectively reduced the level of reactive oxygen
      species (ROS) in fibroblasts after H2O2 treatment which allowed maintaining their
      survival at the level of control cells. Pretreatment of the cells with CF for one
      day ensured the maintenance of normal levels of ROS during the investigated time
      period in the fibroblasts subjected to H2O2 treatment, and reduced H2O2-induced
      cell death by almost a third compared to control cells. The introduction of CF in
      culture medium after ischemia showed no influence on Hsp70 synthesis, but led to
      decrease in GRP78 synthesis, raised after ischemia, to the control level,
      indicating a resolve of the endoplasmic reticulum (ER) stress and functional
      normalization of ER.

PMID- 22997735
TI  - [Polyadenylated RNA and mRNA export factors in extrachromosomal nuclear domains
      of vitellogenic oocytes of the insect Tenebrio molitor].
AB  - The nucleus ofvitellogenic oocytes of the yellow mealworm, Tenebrio molitor,
      contains a karyosphere that consists of the condensed chromatin embedded in an
      extrachromosomal fibrogranular material. Numerous nuclear bodies located freely
      in the nucleoplasm are also observed. Amongst these bodies, counterparts of
      nuclear speckles (= interchromatin granule clusters, IGCs) can be identified by
      the presence of the marker protein SC35. Microinjections of fluorescently tagged
      methyloligoribonucleotide probes 2'-O-Me(U)22, complementary to poly(A) tails of
      RNAs, revealed poly(A)+ RNA in the vast majority of IGCs. We found that all T.
      molitor oocyte IGCs contain heterogeneous ribonucleoprotein (hnRNP) core protein
      Al that localizes to IGCs in an RNA-dependent manner. The extrachromosomal
      material of the karyosphere and a part of nucleoplasmic IGCs also contain the
      adapter protein Aly that is known to provide a link between pre-mRNA splicing and
      mRNA export. The essential mRNA export factor/receptor NXF1 was observed to
      colocalize with Aly. In nucleoplasmic IGCs, NXF1 was found to localize in an RNA
      dependent manner whereas it is RNA-independently located in the extrachromosomal
      material of the karyosphere. We believe our data suggest on a role of the
      nucleoplasmic IGCs in mRNA biogenesis and retention in a road to nuclear export.

PMID- 22997736
TI  - [Assembly of actin filaments induced by sequestration of membrane cholesterol in
      transformed cells].
AB  - Cholesterol is one of the major lipid components of plasma membrane and it plays
      an important role in various signaling processes in mammalian cells. Our study
      focused on the role of membrane cholesterol in organization and dynamics of actin
      cytoskeleton. Experiments were performed on cultured transformed cells
      characterized by weakly developed actin network and reduced stress fibers--human
      embryonic kidney HEK293 cells, epidermoid larynx carcinoma HEp2 cells and mouse
      fibroblasts 3T3-SV40. Using F-actin labeling with rhodamine-phalloidin, actin
      cytoskeleton rearrangements were analyzed after sequestration of membrane
      cholesterol by cyclic oligosaccharide methyl-beta-cyclodextrin, and polyene
      macrolide antibiotic filipin. In cells treated with methyl-beta-cyclodextrin or
      filipin, similar processes of actin cytoskeleton reorganization involving
      filament assembly were revealed. In carcinoma HEp2 cells and fibroblasts 3T3
      SV40, cholesterol-sequestering reagents induced intensive stress fiber formation
      and enhanced cell spreading which corresponded to reversion of transformed
      phenotype. The rearrangements of cytoskeleton are likely initiated by disruption
      of lipid raft integrity that is critically dependent on the level of the membrane
      cholesterol.

PMID- 22997737
TI  - [The distribution of catecholamine-containing neurons in the brain of Pagurus
      middendorffii and Paralithodes camtschaticus (Anomura, Decapoda)].
AB  - Immunocytochemical methods using an antibody raised against tyrosine hydroxylase
      (TH) were investigated the distribution of catecholamine-containing neurons in
      the brain of two species of crustacean Pagurus middendorffii and Paralithodes
      camtschaticus. Morphologically different types of TH-immunoreactive neurons are
      found in the cell clusters in the protocerebrum, deutocerebrum, and tritocerebrum
      of divisions the brain in both species studied crustaceans. The similarities and
      differences in topography, numbers and morphology of TH-positive neurons in the
      different structures of the brain in the hermit crab and king crab are discussed.

PMID- 22997738
TI  - [A new approach to the electrostatic stabilization of cations in the aqueous
      cavity of K+ channel: the role of nonlocal-electrostatic effects].
AB  - Methods of nonlocal electrostatics, applied to ion channels in our previous
      papers, are used to analyze the stability of K+ in the aqueous cavity of K+
      channel. Other authors used formulas of classical electrostatics to calculate the
      energy of K+ in the aqueous cavity of KcsA. Using a new formulation of nonlocal
      electrostatic theory, we obtained a formula for the image force energy acting on
      K+, which is in the center of a spherical cavity of K+ channel. It is shown that
      nonlocal-electrostatic effects in the aqueous cavity of K+ channel leads to a
      decrease in the energy K+ on 4kT compared with the calculation by the formulas of
      classical electrostatics.

PMID- 22997739
TI  - [Microfocus radioimaging in the evaluation of bone regeneration in patients with
      congenital fissures of the alveolar process].
AB  - Congenital fissures of the alveolar process and hard palate are one of the
      severest pathologies of the teeth and jaws. Plain magnification microfocus
      radiography and microfocus radioimaging of the upper jaw with bite occlusion are
      the radiodiagnostic methods of choice for the evaluation of bone defects and
      regenerative processes. To study the regenerative processes, 52 patients aged 10
      16 years with congenital fissures of the alveolar process and hard palate were
      examined after bone reparative surgery. A bone block from the mental region of
      the lower jaw, or cancellous iliac crest tissue or biocomponents materials were
      used to close maxillary alveolar process bony defect. Early and late
      postoperative osteoreparative processes were evaluated applying plain
      magnification radiography and microfocus radioimaging. The first signs of
      osteointegration were observed one month after surgery; the most active processes
      were detected in the patients in whom a mandibular bone block was employed as an
      autograft. The patients with a cancellous iliac autograft were found to have
      partial bone resorption in a number of cases at 6 and 9 months.

PMID- 22997740
TI  - [Capabilities of ultrasound study in the differential diagnosis of neoplasms of
      the major salivary glands].
AB  - Seventy patients aged 20 to 75 years with suspected parotid gland disease were
      examined to study the capabilities of an ultrasound study in the diagnosis of
      neoplasms of the major salivary glands. B-mode ultrasonography and color Doppler
      imaging presented a means of detecting the presence of masses in the gland, their
      topography and dimensions, and specific vascularization, which allowed the option
      and scope of treatment to be planned.

PMID- 22997741
TI  - [Radiodiagnosis of cervical spine lesions].
AB  - The radiation examination of 728 victims of acute spinal column and cord
      injuries, admitted to Omsk City Emergency Medicine Hospital One in the period
      2008-2011, was analyzed. The main cause of spinal column injuries was catastrophe
      (68.7%), vehicle-related trauma (22.3%), and others (9%). Injuries to the
      cervical segments of the spinal cord constituted 10.5%. The 5th and 6th cervical
      vertebrae were most commonly damaged. Spinal cord injuries were multifocal in
      about 46.2% of cases. The diagnostic algorithm of instrumental studies in the
      acute period of spinal injury was performed in the following sequence:
      spondylograms in two projections (77%), those in special positions (3%),
      multislice spiral computed tomography (75%), and magnetic resonance imaging
      (22%). Multislice spiral computed tomography was used as a primary diagnostic
      method for vertebral column fractures in patients with multisystem trauma and
      highly probable spine injury without previous radiography.

PMID- 22997742
TI  - [Comparative capacities of radiation studies in the diagnosis of circumscribed
      peritonitis in case of duodenal microperforation at different stages of emergency
      medical care].
AB  - The results of ultrasound (US) and X-ray studies were retrospectively studied in
      the diagnosis of circumscribed peritonitis in case of microperforation from
      duodenal ulcers at different stages of emergency medical care. Analysis of the
      findings has demonstrated that on admission and in its first hours the most
      effective diagnostic method is plain radiography that enables free gas
      accumulation to be found under the diaphragm and US study is of low informative
      value. Repeat targeted US study using expert-class scanners, with the well stated
      task based on clinical laboratory findings, is a high-informative diagnostic
      technique for circumscribed peritonitis in case of duodenal perforations.

PMID- 22997743
TI  - [Current technologies of radiodiagnosis for pelvic injuries].
AB  - The current requirements for technologies of examination of victims with pelvic
      injuries of varying severity determine the high urgency of radiodiagnostic
      methods. The paper underlines the need for a comprehensive approach in the
      diagnostic process comprising radiography and multislice computed tomography. The
      methodic aspects of the latter are covered; emphasis is laid on the need for
      standardizing protocols depending on clinical tasks in order to improve the
      quality of the diagnosis of pelvic fractures of varying duration, to detect
      pelvic organ injuries, to make preoperative examination, and to monitor the
      treatment of this group of patients.

PMID- 22997744
TI  - [Value of magnetic resonance imaging in the diagnosis of recurrent colorectal
      cancer].
AB  - To diagnose recurrent colorectal cancer is an urgent problem of oncoproctology.
      Eighty patients with suspected recurrent colon tumor were examined. All the
      patients underwent irrigoscopy, colonoscopy, magnetic resonance imaging of the
      abdomen and small pelvis. The major magnetic resonance symptoms of recurrent
      colon tumors were studied; a differential diagnosis of recurrent processes and
      postoperative changes at the site of intervention was made.

PMID- 22997745
TI  - [Role of multislice spiral computed tomographic angiography in the treatment of
      uterine myoma].
AB  - The study was undertaken to enhance the diagnosis, treatment, and rehabilitation
      of patients with uterine myoma, by applying multislice spiral computed
      tomographic angiography (MSCTA) during uterine artery embolization. One hundred
      and twenty patients were divided into two groups: 1) 75 reproductive-age patients
      who underwent MSCTA before and after uterine artery embolization; 2) 45
      reproductive-age patients who had previously undergone the latter according to
      the standard protocol. The main criteria for assessing the long-term results of
      treatment were patient complaints, the state of menstrual cycle and reproductive
      function, the sizes of the uterus and myomatous nodules, the signs of blood
      supply and growth of the latter, the presence or absence of new nodules. The most
      common types of the origin of the uterine arteries were visualized; the angle of
      uterine artery origin was measured. An algorithm for MSCTA study was elaborated.

PMID- 22997746
TI  - [The diagnosis and treatment of congenital preaural fistula].

PMID- 22997747
TI  - [Endovascular isolation of the left atrial auricle using a watchman device: first
      clinical experience].

PMID- 22997748
TI  - [Clinical case of successful use of radiodiagnostic techniques in multifocal
      extranodal lymphoma].

PMID- 22997749
TI  - [The state-of-the-art of the diagnosis of oral and oropharyngeal cancer].

PMID- 22997750
TI  - [Current radiation diagnostic techniques in the estimation of the extent of
      cancer of the endometrium and cervix uteri].

PMID- 22997751
TI  - [Contemporary work conditions and occupational morbidity in metallurgists].
AB  - Based on analysis of materials provided by Central Council of Russian Federal
      Coal Miners Trade Union, the authors assessed contemporary work conditions and
      occupational morbidity among workers engaged into iron industry. In these
      enterprises, a total of 68.4% of certified workplaces are assigned to hazardous
      and jeopardy class (3 and 4 degree of variable hazards). The article covers
      number of workplaces with various work condition classes in 9 metallurgy
      enterprises having considerable differences. The authors defined suggestions on
      improving activity to certify workplaces. In iron industry enterprises, level of
      occupational morbidity remains high (in 2010--17.85 cases per 10,000 workers
      examined), analysis revealed growth trend of the morbidity over 2002-2010. The
      morbidity materials are analysed for separate diseases, for occupational traits
      and among female workers. The authors defined suggestions on preventing
      occupational morbidity among metallurgists.

PMID- 22997752
TI  - [Chronic inflammatory and dystrophic diseases of the eye anterior segment and
      their association with genetic polymorphisms in workers of metallurgic industry].
AB  - The ophthalmologic investigation of workers of the two metallurgical enterprises
      has shown that 1045 persons (55%) from 1911 observed workers suffer chronic
      diseases of a forward piece of eyes. Chronic inflammatory diseases (blepharitis,
      conjunctivitis and blepharoconjunctivitis) are found at 28,9% of them, and
      dystrophic diseases (pinguecula/pterygium)--at 25,8%. Among metallurgists (1801
      persons) ophthalmopathy was found in 2, 2 times more often than at persons in
      control group (110 observed engineers and managers). Two polymorphisms of
      cytochrome P450 1A1 (CYP1A1) and P-450 2E1 (CYP2E1) genes were defined in 91
      workers, by the method of allele-specific polymerase chain reaction. It is
      revealed that CYP1A1 Ile462Val polymorphism associates with pinguecula/pterygium,
      raising risk of their development almost in 3 times, unlike CYP 2E1 -1293G/C
      polymorphism. Development of chronic inflammatory diseases is not connected with
      tested polymorphisms.

PMID- 22997753
TI  - [Quality of life in cryolite production workers depending on length of service].
AB  - Federal budgetary establishment of a science "the Ekaterinburg medical centre of
      science of preventive maintenance and health protection of workers industrial
      plants". Findings are that adaptation level and life quality parameters
      progressively decrease with longer length of service. The most unfavorable
      parameters are seen in cryolite production workers with length of service over 20
      years and in age group of 45-55 years. Conclusion is that treatment and
      prevention are necessary.

PMID- 22997754
TI  - [Biochemical parameters of cardiovascular pathology risk in automobile drivers].
AB  - Examination of 94 city bus drivers with long length of service revealed changes
      in lipid metabolism and C-reactive protein level, dependent on the examinees' age
      and length of service. Matching the biochemical parameters and clinical data
      proved that dyslipoproteinemia and serum C-reactive protein level could indicate
      cardiovascular risk in city bus drivers.

PMID- 22997755
TI  - [Pharmacologic correction of hypoxia in patients with acute cerebral failure due
      to acute poisoning with carbon monoxide and combustion products].
AB  - The article deals with the materials, which have been received in the process of
      the examination and treatment of 48 patients with acute severe carbon monoxide
      and burning products poisonings on fires. It has been registered that the
      including of citoflavin into the complex program of the intensive therapy of
      acute severe carbon monoxide and burning products poisonings on fires leads to a
      decrease of hypoxia and manifestations of acute toxicohypoxic cerebral
      deficiency, which significantly improves the clinics of acute severe poisonings.

PMID- 22997756
TI  - [Prophylaxis of carbon bisulphide poisoning effects on lipid component of
      erythrocyte membrane in experiment].
AB  - Preventive injection of "Kalifen" extract of high cranberry before and during
      intoxication with carbon bisulphide appeared to preserve lipid component of RBC
      membrane in rats.

PMID- 22997757
TI  - [Possibility of the liver ultrastructure recovery in intoxication with heavy
      metals salts].
AB  - Experimental studies helped to reveal ultrastructural changes in hepatocytes,
      caused by prolonged exposure to heavy metals salts taken in combination and
      ratios characteristic to soil contents near Almalyk mining and smelting
      enterprise. The authors demonstrated possibility of liver structural recovery via
      enterosorption with additional antioxidant therapy.

PMID- 22997758
TI  - [Toxic effects of cadmium on the human body (literature review)].
AB  - A review of the literature about the toxic effects of cadmium on the human body.
      We describe a patient with clinical and biochemical signs of an attack of acute
      porphyria imitated or severe lead poisoning. In the patient's blood was revealed
      a 3-fold, compared to the allowable rate, increase of cadmium in the normal lead
      content. We discuss the etiologic role of cadmium and the possible pathogenetic
      mechanisms of this pathological condition.

PMID- 22997759
TI  - [Contemporary pharmacotherapy of arterial hypertension in medical personnel].
AB  - The efficiency of cardosten was investigated in medical personnel with mild
      arterial hypertension. The reliable antihypertensive activity of cardosten was
      shown.

PMID- 22997760
TI  - [Prevention of stress-related disorders in medical personnel].
AB  - Study covered female surgeons subjected to occupational stress complex
      (psychoemotional, chemical, work intensity, etc). Prophylactic intake of
      biologically active food supplement made of high cranberry appeared to relieve
      tension of antioxidant and antiradical defence systems, increased activation and
      stress, to normalize carbohydrates metabolism parameters.

PMID- 22997761
TI  - [The nanotech, the "Mano" and the clinical microbiology].

PMID- 22997762
TI  - Detection of the ompA gene of Chlamydophila pecorum in captive birds in
      Argentina.
AB  - Bacteria belonging to the family Chlamydiaceae cause a broad spectrum of diseases
      in a wide range of hosts, including humans, other mammals and birds. However,
      very little is known about chlamydial infections in birds in our region. In the
      present study, we examined 28 clinically normal birds in illegal captivity that
      were confiscated in the province of C6rdoba, Argentina. The objective was to
      detect Chlamydophila spp. in cloacal swabs by genetic analysis of the ompA gene.
      Nested-PCR of the ompA gene identified five samples as Chlamydophila pecorum and
      the sequence analysis demonstrated the presence of the ompA gene of C. pecorum in
      these birds. On the other hand, Chlamydophila psittaci was not detected. These
      birds could be either asymptomatic reservoirs or subclinical carriers of C.
      pecorum. This is the first report of the detection of C. pecorum in Argentina.

PMID- 22997763
TI  - [Two multidrug-resistant Salmonella infantis isolates behave like hypo-invasive
      strains but have high intracellular proliferation].
AB  - In this work, plasmid-encoded virulence factors in two Salmonella Infantis
      isolates carrying multiresistance plasmids were investigated. In addition, their
      invasion and proliferative ability in non-phagocytic cells was studied. None of
      them showed the typical determinants of virulence plasmids (spy operon). The
      invasion assays of S. Infantis isolates on eukaryotic cells showed a decreased
      ability to invade but they remained and proliferated in the cytoplasm regardless
      of having used a permissive (HeLa) or non-permissive (NRK) cell line. Finally,
      there was no microscopic evidence suggesting a bactericidal effect of these
      eukaryotic cell lines on the isolates tested.

PMID- 22997764
TI  - [Development and preliminary assessment of a recombinant canarypox virus as an
      antirabic vaccine candidate].
AB  - Development and preliminary assessment of a recombinant canarypox virus as an
      antirabic vaccine candidate. In Argentina, rabies is limited to some northern
      provinces. Availability of new vaccines abolishing the handling of the rabies
      virus and allowing disease control has regional and national strategic
      importance. Vaccines based on recombinant poxviruses have been successfully used
      as antirabic vaccines worldwide. Although these systems are not commercially
      available, the platform to obtain recombinant canarypox viruses (CNPV) has been
      previously set up in our laboratory. The aim of this work was the development and
      evaluation of an antirabic vaccine candidate based on recombinant CNPV expressing
      the rabies virus (RV) glycoprotein G (RG). A recombinant virus (CNPV-RG)
      expressing the RG coding sequence was designed. Inoculation of mice with this
      virus induced high RV seroneutralizing antibodies (3.58 and 9.76 IU/ml after 1 or
      2 immunizations, respectively) and protected 78% of intracerebrally RV-challenged
      animals. In addition, it was determined that CNPV-RG has a relative potency of
      3.5 IU/ml. The obtained results constituted the first stage of CNPV-RG evaluation
      as antirabic vaccine candidate. Further assays will be necessary to confirm its
      utility in species of veterinary interest.

PMID- 22997765
TI  - [Genotypic characterization of toxigenic Escherichia coli isolated from pigs with
      postweaning diarrhea (PWD) and edema disease (ED)].
AB  - The purpose of this work was to characterize 47 Escherichia coli strains isolated
      from 32 pigs diagnosed with postweaning diarrhea and three pigs with edema
      disease by PCR. Forty two (95.5 %) of the strains isolated from diarrheic pigs
      were characterized as enterotoxigenic E. coli (ETEC) and 2 (4.5 %) as Shiga toxin
      producing E. coli (STEC). Fourteen (33.3 %) ETEC strains were positive for
      est/estII/fedA genes. The most complex genotype was eltA/estI/faeG/aidA. Strains
      isolated from pigs with ED were classified as porcine STEC and were stx2e/aidA
      carriers. Eleven (25 %) strains carried the gene encoding adhesin protein AIDA-I.
      However, genes coding for F5, F6, F41, intimin and Paa were not detected. The
      development of vaccines generating antibodies against prevalent E. coli adhesins
      in Argentina could be useful for the prevention of PWD and ED.

PMID- 22997766
TI  - [CHROMagar KPC. Comparison with the method proposed by the Centers for Disease
      Control and Prevention (CDC, USA) for rectal screening and evaluation of false
      positive results].
AB  - Eighty one rectal swabs (RS) were cultured on CHROMagar KPC and the CDC method.
      Of the 81 samples, 9 were positive for KPC-producing Klebsiella pneumoniae on
      CHROMagar KPC, and 6 for the CDC method. CHROMagar KPC had two false positive
      (FP) results: 1 K. pneumoniae and 1 Acinetobacter sp. FP results on the CDC
      method were: 25 Acinetobacter spp., 2 Escherichia coli and 4 K. pneumoniae:
      CHROMagar KPC yielded a better recovery of KPC-producing bacteria and less FP
      results than CDC method. In order to evaluate FP results on CHROMagar KPC, 1247
      RS were cultured and yielded 1021 negatives, 171 KPC-producing K. pneumoniae and
      55 FP (4.4 %). Because of the FP results growing on CHROMagar KPC, KPC must be
      phenotypically confirmed in the bacteria isolated.

PMID- 22997767
TI  - Two cases of urinary tract infection caused by Shiga toxin-producing Escherichia
      coli O157:H7 strains.
AB  - STEC strains can infect extra-intestinal sites such as the human urinary tract
      and sometimes cause severe complications. We report two cases of urinary tract
      infection caused by STEC in two elderly women with comorbidities. Although both
      strains belonged to the O157:H7 serotype and carried genes associated with severe
      illness, none of the patients developed hemolytic uremic syndrome (HUS). These
      findings provide additional evidence for the presence of these agents in our
      country and in the region, and highlight the need to maintain an active
      surveillance system of HUS cases, placing special emphasis on the study of other
      sites of infection in patients with non-diarrheal HUS.

PMID- 22997768
TI  - [Contribution of the PCR assay to the diagnosis of Mansonella ozzardi in endemic
      areas of Argentina].
AB  - Mansonella ozzardi is a tissue-dwelling parasitic nematode, the causative agent
      of mansonelliasis in almost all Latin American countries. It has been described
      along the Argentine Yungas region. The microscopic diagnosis can yield false
      negative test results at low microfilaremia levels. The aim of this study was to
      optimize the molecular diagnostic technique and compare it with the Knott's
      method and standard blood smear procedures (thin blood films and thick smears) in
      92 blood samples of individuals from an endemic area. The PCR technique followed
      by the sequencing of the amplified product yielded 100 % sensitivity compared to
      the Knott's test, which is considered a reference method. Seven more cases of
      this parasitosis could only be identified with the molecular technique.

PMID- 22997769
TI  - [Carriage and characterization of Staphylococcus aureus in food handlers].
AB  - Staphylococcus aureus causes food poisoning due to its ability to produce
      enterotoxins. Food handlers carrying enterotoxin-producing S. aureus can
      contaminate food, thus leading to food poisoning. Samples were obtained from 88
      food handlers in the Province of Misiones, Argentina. S. aureus was isolated from
      nasal swaps and PCR amplification was performed for genes encoding staphylococcal
      enterotoxins. A total of 37.5 % food handlers were positive for S. aureus.
      Expression of enterotoxin genes was found in 13 of the 33 (39.4 %) S. aureus
      isolates studied, accounting for 14.7 % of food handlers. Gene sea was detected
      in 10 isolates followed by gene sec in 3 isolates. All isolates were susceptible
      to teicoplanin, gentamicin and rifampicin. Four isolates were resistant to
      methicillin whereas 2 isolates were resistant to clindamycin and erythromycin.
      These results constitute a critical alert and indicate the need for developing
      rational measures to reduce the potential risk of food poisoning.

PMID- 22997770
TI  - Grape stalks as substrate for white rot fungi, lignocellulolytic enzyme
      production and dye decolorization.
AB  - The aim of this work was to evaluate the potential of grape stalks, an
      agroindustrial waste, for growth and lignocellulolytic enzyme production via
      solid-state fermentation, using the following three white rot fungi: Trametes
      trogii, Stereum hirsutum and Coriolus antarcticus. The decolorization of several
      dyes by the above mentioned cultures was also investigated. Similar values of dry
      weight loss of the substrate were measured after 60 days (33-43 %). C.
      antarcticus produced the highest laccase and Mn-peroxidase activities (33.0 and
      1.6 U/g dry solid). The maximum endoglucanase production was measured in S.
      hirsutum cultures (10.4 U/g), while the endoxylanase peak corresponded to T.
      trogii (14.6 U/g). The C. antarcticus/grape stalk system seems potentially
      competitive in bioremediation of textile processing effluents, attaining
      percentages of decolorization of 93, 86, 82, 82, 77, and 58% for indigo carmine,
      malachite green, azure B, remazol brilliant blue R, crystal violet and xylidine,
      respectively, in 5 h.

PMID- 22997771
TI  - Biodegradation of phenol in static cultures by Penicillium chrysogenum ERK1:
      catalytic abilities and residual phytotoxicity.
AB  - A phenol-degrading fungus was isolated from crop soils. Molecular
      characterization (using internal transcribed spacer, translation elongation
      factor and beta-tubulin gene sequences) and biochemical characterization allowed
      to identify the fungal strain as Penicillium chrysogenum Thom ERK1. Phenol
      degradation was tested at 25 degrees C under resting mycelium conditions at 6,
      30, 60, 200, 350 and 400 mg/l of phenol as the only source of carbon and energy.
      The time required for complete phenol degradation increased at different initial
      phenol concentrations. Maximum specific degradation rate (0.89978 mg of
      phenol/day/mg of dry weight) was obtained at 200 mg/l. Biomass yield decreased at
      initial phenol concentrations above 60 mg/l. Catechol was identified as an
      intermediate metabolite by HPLC analysis and catechol dioxygenase activity was
      detected in plate assays, suggesting that phenol metabolism could occur via ortho
      fission of catechol. Wheat seeds were used as phytotoxicity indicators of phenol
      degradation products. It was found that these products were not phytotoxic for
      wheat but highly phytotoxic for phenol. The high specific degradation rates
      obtained under resting mycelium conditions are considered relevant for practical
      applications of this fungus in soil decontamination processes.

PMID- 22997772
TI  - Bioprospection of marine microorganisms: potential and challenges for Argentina.
AB  - The marine environments of Argentina have a remarkable extension, as well as high
      biological productivity and biodiversity of both macro- and microorganisms.
      Despite having a great potential for biotechnological applications, the
      microorganisms inhabiting these ecosystems remain mostly unexplored and
      unexploited. In this review, we study the research topics and the interactions
      among Argentinean laboratories, by analyzing current articles published on
      biotechnology-related marine microbiology by researchers of this country. In
      addition, we identify the challenges and opportunities for Argentina to take
      advantage of the genetic potential of its marine microorganisms. Finally, we
      suggest possible actions that could improve the development of this research
      field, as well as the utilization of this knowledge to solve societal needs.

PMID- 22997773
TI  - [Endosymbiosis of Arcobacter butzleri in Acanthamoeba castellanii].

PMID- 22997774
TI  - [Kerion celsi].

PMID- 22997775
TI  - [Zoonotic potential of raw cow's milk in the Czech Republic].
AB  - BACKGROUND: To assess current microbiological risks of raw cow's milk. The
      presented work reports the prevalence of selected bacteria on Czech dairy farms
      in 2010 and compares the results with a similar study in 2002. MATERIAL AND
      METHODS: The prevalence of bacteria was studied by culture methods using milk
      filters made from non-woven fabric collected from dairy farms throughout the year
      2010. Together 260 filters from 65 dairy farms were tested. The prevalence of
      Campylobacter spp., Listeria monocytogenes, Staphylococcus aureus, Escherichia
      coli O 157 and Salmonella spp. in filters was tested. In staphylococci, genes
      encoding enterotoxin-production were studied. In Campylobacter spp., resistance
      to antibiotics was ascertained. RESULTS: In 2010, the prevalence rates of
      selected bacteria on farms were as follows: Campylobacter spp. 3%, Escherichia
      coli O 157 0.4%, Salmonella spp. 0.8%, Listeria monocytogenes 10% and
      Staphylococcus aureus 31%. In 12% of the tested filters, S. aureus with the
      genetic make-up for enterotoxin production was isolated. Antibiotic resistance in
      Campylobacter spp. isolated from dairy farms is different from that in human or
      poultry isolates. CONCLUSION: Raw cow's milk contains bacteria capable of causing
      human alimentary tract diseases. The above microbiological risks for consumers
      are eliminated by proper storage conditions (below 10 degrees C) and heat
      treatment (boiling) of raw milk.

PMID- 22997776
TI  - [Occurrence and typing of Listeria monocytogenes isolated from raw cow's milk
      collected on farms and from vending machines].
AB  - BACKGROUND: Evaluation of the incidence and characteristics of L. monocytogenes
      in samples of raw cow's milk collected on farms (bulk tank milk samples) and from
      vending machines. MATERIAL AND METHODS: Detection of L. monocytogenes and
      enumeration were carried out according to EN/ISO 11290--1, 2. Strains were
      characterised by serotyping and macrorestriction analysis using pulsed-field gel
      electrophoresis. RESULTS: The presence of L. monocytogenes was detected in 3,2 %
      (11/346) of bulk tank milk samples and 1,8 % (4/219) samples of raw cow's milk
      from vending machines. Findings of L. monocytogenes in raw milk were sporadic.
      Only on one farm strains of L. monocytogenes were detected repeatedly. Thirteen
      strains of L. monocytogenes belonged to serotype 1/2a, two strains to serotype
      1/2b and one to serotype 4b. Macrorestriction analysis revealed considerable
      heterogeinity of profiles, with nine different pulsotypes being detected.
      Pulsotype 711 was the most frequent. This pulsotype was found on three different
      farms. CONCLUSIONS: The incidence of L. monocytogenes in raw cow's milk is
      relatively low in the Czech Republic. The results confirmed that some clones of
      L. monocytogenes from raw milk are identical with food and human strains.

PMID- 22997777
TI  - [Visceral leishmaniasis (two case reports)].
AB  - Two cases of imported visceral leishmaniasis are described. The first patient was
      a 32-year-old Czech man who developed leishmaniasis 5 months after a holiday in
      Italy (Bibione). The second patient was a 62-year-old Czech man who developed
      leishmaniasis 18 months after visiting Croatia (Makarska); the disease began
      after a course of chemotherapy due to metastasizing testicular tumor. Both
      patients were successfully treated with amphotericin B lipid complex (Abelcet).
      Difficulties in establishing the correct diagnosis of visceral leishmaniasis are
      discussed.

PMID- 22997778
TI  - [Methods used to detect mycobacterioses in humans--assessment of advantages and
      disadvantages of mycobacterial identification by sequencing analysis].
AB  - The isolation of potentially pathogenic mycobacteria (PPM) from clinical
      specimens has become very frequent in the last years. Such organisms are
      typically environmental and occasionally pathogenic for humans. Standard
      diagnosis of mycobacterial infections relies on direct examination and culture.
      Nowadays, molecular tools are available, allowing quicker accurate diagnosis.
      Detection of PPM can be performed directly from clinical samples, although in
      most cases identification is carried out after isolation. Sequencing of genomic
      targets (such as 16S rRNA, rpoB or hsp65) allows accurate and quick
      identifications but has some technical limitations. Problems concerning
      sequencing analysis used for PPM identification together with description of
      available algorithms for PPM identification are the major objectives of this
      review.

PMID- 22997779
TI  - [Brucella suis--a little-known zoonotic agent].
AB  - Brucellosis is a rare but serious bacterial zoonosis. Officially, the Czech
      Republic is among countries that are free from brucellosis in livestock. In the
      country, sporadic imported human infections may occur, caused by e.g. Brucella
      melitensis. In wild hare populations, however, rare cases of infection caused by
      Brucella suis are still observed, potentially threatening humans. The short
      communication reports two cases of hare brucellosis in Moravia, Czech Republic,
      and experiences with isolate identification by the MALDI-TOF method.

PMID- 22997780
TI  - [Clinical safety research of penetrating acupuncture at the head points for
      cerebral hemorrhage at the acute stage].
AB  - OBJECTIVE: To verify the safety of penetrating acupuncture at the head points for
      cerebral hemorrhage at the acute stage. METHODS: Sixty cases of cerebral
      hemorrhage at the acute stage were selected and randomized into a western
      medication group and a head-point group, 30 cases in each one. In the western
      medication group, the anti-cranial pressure and anti-blood pressure program was
      administered with the conventional intravenous infusion of Sodium Nitroprusside,
      Mannite, etc. In the head-point group, on the basis of the treatment as the
      western medication group, the penetrating acupuncture at the head points was
      supplemented. For consciousness disturbance, Taiyang (EX-HN 5), Benshen (GB 13)
      and penetrating needling from Shenting (GV 24) to Shangxing (GV 23) were
      selected. For headache, the penetrating needling was adopted from Shangxing (GV
      23) to Yintang (EX-HN 3) and from Fengchi (GB 20) to Fengchi (GB 20). For
      disturbance of urination and defecation, the penetrating needling was adopted
      from Baihui (GV 20) to Sishencong (EX-HN 1). For aphasia, the penetrating
      needling was adopted from Fengfu (GV 16) to Yamen (GV 15), etc. For facial
      paralysis, the penetrating needling from Dicang (ST 4) to Jiache (ST 6) and
      Xiaguan (ST 7) were selected. For paralysis, the penetrating needling was adopted
      from Baihui (GV 20) to Taiyang (EX-HN 5), etc. Before and after treatment, the
      changes in cerebral hemorrhagic volume, the results of blood, urine and stool
      routine examination, the situations of the life indices such as heart, liver and
      kidney functions, blood pressure, respiration and heart rate were observed, as
      well as the impacts on ECG. RESULTS: The cranial CT sania cn indicated that the
      rate of the basic and significant absorption of hematoma was 80.0% (24/30) in the
      head-point group, which was superior to 56.7% (17/30) in the western medication
      group (P < 0.05). Before and after treatment, the results of blood, urine and
      stool routine examination and the life indices such as blood pressure,
      respiration and heart rate were all in the normal scope for the patients in the
      head-point group (all P > 0.05). There were no any abnormal changes in liver and
      kidney functions. In the head-point group, the abnormality rate of ECG was lower
      obviously than that in the western medication group [16.7% (5/30) vs 43.3%
      (13/30), P < 0.05]. CONCLUSION: The penetrating acupuncture at the head points is
      safe in the treatment of cerebral hemorrhage at the acute stage.

PMID- 22997781
TI  - [Comparative study on effects between electroacupuncture and acupuncture for
      spastic paralysis after stroke].
AB  - OBJECTIVE: To observe the differences of therapeutic effect of spastic paralysis
      after stroke between electroacupuncture and acupuncture and explore the
      mechanism. METHODS: Sixty-four cases were randomly divided into an
      electroacupuncture group (n = 33) and an acupuncture group (n = 31). Both groups
      were treated with Bobath facilitation techniques and medicine treatments. Quchi
      (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Sanyinjiao (SP 6), et al. on the
      affected side were selected in each group. The needle was retained for 30 min,
      and the manipulation was applied for 1 min in the acupuncture group, and
      electroacupuncture was added in the electroacupuncture group. Stroke Impairment
      Assessment Set (SIAS) was adopted to assess the whole function status after
      sroke, and the contents of glutamate (Glu) and gamma-aminobutyric acid (GABA) in
      serum and clinical efficacy were observed in the two groups. RESULTS: The SIAS
      score increased after treatment as compared with that before treatment in either
      group (both P < 0.01), and the electroacupuncture group was superior to the
      acupuncture group (P < 0.01); the content of Glu in blood serum and ratio of
      Glu/GABA reduced, while the content of GABA in serum increased after treatment as
      compared with those before treatment in either group (all P < 0.01), but the
      improvement of above indices were much more apparently in the electroacupuncture
      group as compared with those in the acupuncture group (P < 0.01, P < 0.05); the
      total effective rate of 90.9% (30/33) in the electroacupuncture group was
      superior to that of 83.9% (26/31) in the acupuncture group (P < 0.05).
      CONCLUSION: Electroacupuncture can improve therapeutic effect of spastic
      paralysis after stroke, it's mechanism may be ralated to ajusting the contents of
      Glu and GABA in serum.

PMID- 22997782
TI  - [Bian-stone therapy for postoperative pain due to artificial abortion].

PMID- 22997783
TI  - [Comparison on efficacy and the safety evaluation on peripheral facial paralysis
      treated with electroacupuncture of different waveforms].
AB  - OBJECTIVE: To use electroacupuncture (EA) of different waveforms to treat
      peripheral facial paralysis and assess the clinical efficacies of 3 kinds of EA
      waveforms (continuous wave, disperse-dense wave and intermittent wave). METHODS:
      One hundred and twenty-nine cases of Bell's palsy were randomly divided into a
      continuous wave group (45 cases), a disperse-dense wave group (40 cases) and an
      intermittent wave group (44 cases). The acupoints were Dicang (ST 4), Jiache (ST
      6), Taiyang (EX-HN 5), Xiaguan (ST 7), Hegu (LI 4), etc. The House-Brackmann (H
      B) scale was used in the assessment on the day of the inclusion, in the 1st, 2nd,
      3rd and 4th sessions of treatment and in 1st and 3rd months of the follow-up
      visit after the end of treatment separately. RESULTS: The cured rates were 68.9%
      (31/45), 60.0% (24/40) and 65.9% (29/44) in the continuous wave group, the
      disperse-dense wave group and the intermittent wave group separately. The results
      of the rank sum test showed that the efficacy comparison among the groups did not
      present the statistically significant difference (P > 0.05). CONCLUSION:
      Electroacupuncture achieves the significant clinical efficacy on peripheral
      facial paralysis and there are no any significant differences in the efficacy
      among the different waveforms. It is suggested that the clinical efficacy of
      electroacupuncture on the disease has nothing significant correlation with the
      waveforms.

PMID- 22997784
TI  - [Embedding catgut acupoint and blood-letting at trigger point for 58 cases of
      primary trigeminal neuralgia].

PMID- 22997785
TI  - [Comparative study on effect of acupoint heat-sensitive moxibustion and Seretide
      on the symptoms of bronchial asthma at chronic persistent stage].
AB  - OBJECTIVE: To observe the difference in the efficacy on the symptoms of bronchial
      asthma at the chronic persistent stage between acupoint heat-sensitive
      moxibustion and western medicine with Seretide. METHODS: Sixty-four cases were
      randomly divided into a heat-sensitive moxibustion group (32 cases) and a western
      medication group (32 cases). In the heat-sensitive moxibustion group, the
      sensitized points located between Feishu (BL 13) and Geshu (BL 17) or in the
      region 6-cun lateral from the 1st and the 2nd intercostal spaces of the chest
      were selected. The heat-sensitive moxibustion was adopted, continuously for 8
      days, once per day. In the later 22 days of the 1st month, 12 treatments should
      be ensured. Two months later, 15 treatments should be guaranteed each month. The
      time of each treatment was 30 to 90 min. Totally 50 treatments were required. In
      the western medication group, Seretide inhaler was adopted, one inhalation each
      time, twice per day, for 3 months totally. The asthmatic symptoms were scored for
      the patients in two groups and the comparison was made between the two groups.
      RESULTS: After 3 months of treatment, the asthmatic symptom scores were all
      improved for the patients in the heat-sensitive moxibustion group and the western
      medication group as compared with those before treatment (both P < 0.05). In 6
      months of follow-up visit, the asthmatic symptom scores in the heat-sensitive
      moxibustion group were stable, but those in the western medication group were
      reduced, there was significant difference between the two groups (P < 0.05).
      CONCLUSION: The acupoint heat-sensitive moxibustion effectively relieves the
      clinical symptoms for the patients with bronchial asthma at the chronic
      persistent stage. Its efficacy is similar to that of Seretide inhaler. But the
      long-term efficacy of the heat-sensitive moxibustion is much better.

PMID- 22997786
TI  - [Observation on therapeutic effect of myofascial pain syndrome of the back in the
      military soldiers treated with moxibustion].
AB  - OBJECTIVE: To provide a set of the self-help and mutual-aid treatment with
      moxibustion to deal with myofasicial pain syndrome (MPS) of the back for the
      military soldiers. METHODS: Fifty-eight cases were randomly devided into a
      moxibustion group (30 cases) and a plaster application group (28 cases). In the
      moxibustion group, the suspended moxibustion was applied to Yanglingquan (GB 34)
      for 15 min. The moxibustion massage device was used to massage the pain area.
      Under the physician's guides, the self-help or mutual-aid treatment was adopted.
      In the plaster application group, Goupi Gao (a black plaster used in TCM) was
      used on the local pain area. The treatment was given once every day in either
      group, lasting for 5 days. The clinical symptom scale, clinical physical sign
      scale, functional disturbance scale, functional disturbance index, comprehensive
      economic benefit and the others were adopted to analyze and compare the clinical
      efficacies between the two groups. RESULTS: Both moxibustion and the plaster
      application achieved a certain efficacy on MPS of the back in the soldiers and
      either of them received the obvious improvements in the clinical symptoms,
      physical signs and functional disturbance (P < 0.01, P < 0.05). The results in
      the moxibustion group were superior to those in the plaster application group (P
      < 0.01, P < 0.05). In terms of the comprehensive economic benefit index, the
      result in the moxibustion group was better than that in the plaster application
      group. The total effective rate was 96.7% (29/30) in the moxibustion group and
      was 35.7% (10/28) in the plaster application group. The efficacy in the
      moxibustion group was superior to that in the plaster application group (P <
      0.01). CONCLUSION: The self-help or mutual-aid treatment with moxibustion
      achieves the satisfactory clinical efficacy on MPS of the back in the military
      soldiers. It reduces the conventional medical cost and the military medical
      expenditure. This therapeutic approach is suitable to be promoted in the
      military.

PMID- 22997787
TI  - [Clinical observation of acute pancreatitis treated with acupoint application
      combined with medicine].
AB  - OBJECTIVE: To explore a better therapeutic method for acute pancreatitis.
      METHODS: Sixty-three cases of acute pancreatitis were randomly divided into an
      observation group (31 cases) and a control group (32 cases). In the control
      group, routine treatment of western medicine included fasting, gastric acid and
      trypsinase secretion inhibition were applied, while acupoint application was
      added in the observation group. Yishu (Extra), Zhongwan (CV 12), Neiguan (PC 6),
      Zusanli (ST 36) and Pishu (BL 20) were selected as the main acupoints. The
      magnetic plaster was applied to the acupoints mentioned and changed once per day.
      Seven days made one session. RESULTS: The cured rate in the observation group was
      90.3% (28/31), which was significantly higher than that of 71.9%, (23/32) in the
      control group (P < 0.05). The recovery time of hyper-serum amylase, hyper-uric
      amylase and hyper-leukocytes in the observation group was significantly shorter
      than that in the control group [(3.5 +/- 0.9) days vs (5.9 +/- 0.8) days, (6.1 +/
      1.5) days vs (10.5 +/- 1.8) days, (6.8 +/- 1.4) days vs (9.7 +/- 1.6) days, all
      P < 0.05]. The hospital stays and expenses in the observation group were
      significantly lower than those in the control group [(7.9 +/- 0.9) days vs (11.7
      +/- 1.4) days, (5.3 +/- 1.1) thousand RMB vs (8.9 +/- 1.5) thousand RMB, both P <
      0.05]. CONCLUSION: Acupoint application combined with routine treatment of
      western medicine is effective and can be considered as a better therapy for acute
      pancreatitis.

PMID- 22997788
TI  - [Long-round needle therapy for 56 cases of lateral epicondylitis].

PMID- 22997789
TI  - [Discussion on the control of treatment amount of acupuncture and moxibustion for
      peripheral facial paralysis].
AB  - To explore the control principles of treatment amount of acupuncture and
      moxibustion for peripheral facial paralysis. (1) Early stage: in this period, the
      selected acupoints should be few, therapy should be easy and simple, and the
      treatment amount should be small and basically constant, which is called constant
      acupoints and amount. (2) Middle stage: the treatment of this stage should be
      given with more acupoints and various therapies, the treatment amount should be
      gradually increasing and reach the peak within a certain time and keep it for an
      appropriate time, which is called increasing acuponts and amount. (3) Late stage:
      the treatment at this stage should be given with more acupoints, lesser
      therapies, and the treatment amount should be gradually decreasding and get the
      valley point within a certain time, which is called more acupoints and less
      amount. (4) Sequelae stage: the selection of acupoints at this stage should be
      focus on areas which there are the obvious symptoms, and solo type of therapy and
      little treatment amount is required, which is called changing acupoints and
      little amount. In a word, the best therapeutic effect could be achieved on
      condition that the control principles of treatment amount for peripheral facial
      paralysis are followed during the clinical practice.

PMID- 22997790
TI  - [Impacts on the skin temperature by the different distances of moxibustion:
      discussion on the safe distance of moxibusiton].
AB  - OBJECTIVE: To observe the impacts of the different distances of moxibustion on
      local skin temperature and provide a safy distance of moxibustion. METHODS: Three
      healthy adult volunteers were included. The pure moxa stick (without other herbs
      mixed together) was used. The moxa-stick moxibustion and the mild moxibustion
      (with moxa box) were applied to Zusanli (ST 36) on the right side and Guanyuan
      (CV 4) respectively. The distance from moxibustion to the local skin was 2 cm, 3
      cm and 4 cm separately. The moxibustion time was limited by 3 cm stick burned
      out. The infrared thermography was adopted to record and store thermal images and
      made the systematic analysis. The same trial was repeated on the second day. The
      means of the skin temperature measured at each acupoint each time was taken as
      the results for the analysis. RESULTS: (1) Moxibustion with moxa box at Guanyuan
      (CV 4): at the distance of 4 cm, the local skin temperature at over 44 degrees C
      [(44.1 +/- 1.3)-(46.7 +/- 1.5) degrees C)] lasted 7 min; at the distance of 3 cm,
      the local skin temperature at over 44 degrees C [(44.1 +/- 1.3)-(49.3 +/- 2.0)
      degrees C] lasted about 10 min and that at over 49 degrees C [(49.0 +/- 2.1)
      (49.3 +/- 2.0) degrees C)] lasted 2 min; at the distance of 2 cm, the observation
      could not be followed due to local burning pain. (2) Moxa-stick moxibustion at
      Zusanli (ST 36): at the distance of 4 cm, the skin temperature was ranged from
      (40.0 +/- 2.0) degrees C to (44.9 +/- 2.3) degrees C; at the distance of 3 cm, in
      1 min of moxibustion, the skin temperature increased over 44 degrees C,
      sustaining in the range from (45.9 +/- 3.0) degrees C to (47.8 +/- 2.0) degrees
      C; at the distance of 2 cm, the observation could not be followed due to local
      burning pain. CONCLUSION: In moxibustion, the closer the moxa stick to the skin
      is, the higher the local skin temperature is. No matter with stick moxibustion or
      box moxibustion, the distance of moxa stick to the skin should be in the range
      from 3 to 4 cm.

PMID- 22997791
TI  - [Electroacupuncture combined with peretration needling for 60 cases of simple
      obesity].

PMID- 22997792
TI  - [Effects of acupotomy lysis on local soft tissue tension in patients with the
      third lumbar vertebrae transverse process syndrome].
AB  - OBJECTIVE: To explore the mechanism of acupotomy lysis in treatment of the third
      lumbar vertebrae transverse process syndrome. METHODS: One hundred and eighty
      patients were randomly assigned into an acupotomy group and an electroacupuncture
      (EA) group, 90 cases in each group. The acupotomy group was treated with
      acupotomy on the tip of the 3rd lumbar vertebrae transverse process (tender
      point) combination with massage manipulation of hyperflexion and hyperextension
      on the waist, once a week for 3 weeks. The EA group was treated with EA at
      bilateral Shenshu (BL 23), Yaoyangguan (GV 3), Ashi point (local tender point)
      and ipsilateral Weizhong (BL 40), 3 times a week for 3 weeks. The 500 g pressure
      displacement and the energy absorption ratio were measured by JZL-II soft tissue
      tension meter and the clinical effect was evaluated by JOA low back pain scale
      before treatment, after treatment and 6 months after treatment. RESULTS: After
      treatment and at follow-up visit, the 500 g pressure displacement in the
      acupotomy group increased significantly (both P < 0.01), but it was decreased
      significantly in the EA group (P < 0.05, P < 0.01). The energy absorption ratio
      in the acupotomy group after treatment and at follow-up visit increased
      significantly (both P < 0.01), and in the EA group, there was no significant
      difference after treatment as compared with that before treatment (P > 0.05), but
      it was increased significantly at follow-up visit (P < 0.01). The total
      therapeutic level distribution in the acupotomy group was better than that in the
      EA group after treatment and 6 months after treatment (P < 0.05, P < 0.01).
      CONCLUSION: Acupotomy therapy can significantly increase the 500 g pressure
      displacement and the energy absorption ratio of the local soft tissue around the
      third lumbar vertebrae transverse process, decrease the local soft tissue tension
      so as to alleviate pain. The clinical effect of the acupotomy is superior to that
      of electroacupuncture.

PMID- 22997793
TI  - [Efficacy observation on osteoarthritis of the knee treated with the
      ultrastructural acupotomy therapy at the counter-Ashi points].
AB  - OBJECTIVE: To compare the difference in the efficacy on osteoarthritis of the
      knee between the ultrastructural acupotomy therapy at the counter-Ashi points and
      the conventional acupuncture-moxibustion therapy. METHODS: Sixty cases were
      randomly devided into an ultrastructural acupotomy therapy group (group A) and a
      conventional acupuncture-moxibustion group (group B), 30 cases in each one. In
      the group A, the ultrastructural acupotomy therapy was applied to the counter
      Ashi points in which pain was alleviated or disappeared on pressure. The
      treatment was given once a week, lasting for 1 month. In the group B, the
      acupuncture-moxibustion therapy was applied to Dubi (ST 35), Neixiyan (EX-LE 4),
      Zusanli (ST 36), Yanglingquan (GB 34), etc. The treatment was given once daily,
      lasting for 1 month. Before and after treatment, the Visual Analogue Scale (VAS),
      Lysholm knee joint scale and the affected knee joint flexion angle were observed
      in the two groups. The clinical efficacy was compared between the two groups.
      RESULTS: After treatment, the scores of VAS, Lysholm knee joint scale and the
      affected knee joint flexion angle were improved obviously as compared with those
      before treatment in either group (P < 0.01, P < 0.05). The results of them in the
      group A were superior apparently to those in the group B (all P < 0.05). The
      total effective rate in the group A was superior to that in the group B [80.0%
      (24/30) vs 60.0% (18/30), P < 0.05]. CONCLUSION: The ultrastructural acupotomy
      therapy at the counter-Ashi points achieves the superior clinical efficacy on
      osteoarthritis of the knee as compared with the conventional acupuncture therapy.
      It relieves pain and improves the motion range of knee joint effectively. It is
      simple in operation and less in treatment frequency.

PMID- 22997794
TI  - [Effect of electroacupuncture on inflammatory injury induced by intestinal
      ischemia/reperfusion in rats].
AB  - OBJECTIVE: To observe the protective effect of electroacupuncture (EA) at
      "Zusanli" (ST 36) on inflammatory injury induced by intestinal
      ischemia/reperfusion (I/R) in rats. METHODS: Forty-eight Wistar rats were
      randomly divided into a sham injury group, a model group, an EA group and a sham
      EA group, 12 rats in each group. Intestinal I/R rat models were established by
      method of clamping with occlusion of superior mesenteric artery (SMA) for 45 min
      followed by reperfusion. The EA group was treated with EA (2.5 mA, 2 Hz/100 Hz,
      0.5 h) at "Zusanli" (ST 36) 30 min before reperfusion, and at the same time, the
      sham EA group was treated with fast insertion at two non-meridian acupoints on
      skin surface (2 cm horizontally away from linea alba abdominis and about 5 cm
      paralleled to cartilago ensiformis downward). No interventions were added on the
      sham injury group and the model group. The degree of pathological injury in
      intestines, water rate of intestines, diamine oxidase (DAO) activity and
      intestinal mucosal blood flow (IMBF) were examined at 1 h and 3 h after
      reperfusion. RESULTS: At 1 h and 3 h after reperfusion, the intestinal
      pathological injury in EA group was significantly attenuated compared with that
      in model group, and the intestinal water rate of (74.00 +/- 2.11)% and (78.78 +/-
      0.80)% in EA group were significantly lower than (80.69 +/- 1.66)% and (83.17 +/-
      2.08)% in model group (both P < 0.01), but DAO of (68.83 +/- 4.31) U/L and (47.84
      +/- 5.57) U/L as well as IMBF of (152 +/- 5.8) PU and (139.8 +/- 6.1) PU in EA
      group were significantly higher than DAO of (32.86 +/- 4.72) U/L, (17.01 +/-
      2.96) U/L as well as IMBF of (124.7 +/- 8.3) PU and (89.4 +/- 13.2) PU in model
      group (all P < 0.01). Meanwhile, the above mentioned changes in sham EA group
      showed no significant differences compared with those in model group (all P >
      0.05). CONCLUSION: Electroacupuncture can not only reduce the inflammatory injury
      induced by intestinal IR but also increase intestinal blood supply so as to
      protect the intestine function.

PMID- 22997795
TI  - [Controlled study on different acupoint-prescription for the acupoint catgut
      embedding therapy in treatment of bronchial asthma].
AB  - OBJECTIVE: To probe into the best acupoint-prescription for the simple acupoint
      catgut embedding therapy in treatment of bronchial asthma. METHODS: Forty-eight
      Wistar rats were randomly divided into six groups: the simple acupoint catgut
      embedding at Feishu (BL 13), Danzhong (CV 17) and Shenshu (BL 23) group (group
      A), the simple acupoint catgut embedding at Shenshu (BL 23) group (group B), the
      simple acupoint catgut embedding at Feishu (BL 13) and Danzhong (CV 17) group
      (group C), Dexamethasone group (group D), model group (group E), and control
      group (group F), 8 rats in each group. The asthmatic models were established by
      Ovalbumin (OVA) except group F. Rats in group A, B and C were treated with catgut
      embedding at the corresponding acupoints from the first experimental day. In
      group E and D, Dexamethasone and sterile were intraperitoneal injected
      respectively from the 15th experimental day, once a day for 2 weeks consistantly.
      No interventions were added on group F. For the six groups, the symptoms of
      asthmatic attack were observed and the pathologic changes of lung tissue were
      examined. RESULTS: (1) The times of sneeze and rhinocnesmus scratching nose in
      group E were increased significantly compared with those in group F (both P <
      0.01), but there was no significant difference between group D and F (both P >
      0.05). As compared with that in group E, except the times of sneeze in group C,
      the times mentioned above were decreased significantly in all the treatment
      groups (all P < 0.01). There was no significant difference between group A and D
      (both P > 0.05), but the times mentioned above were increased significantly in
      group B and C as compared with that in group A (all P < 0.01). (2) The symptoms
      of asthmatic attack and the pathologic changes of airway tissue were all
      alleviated in group A, B and C, but a better amelioration was observed in group
      A, with no mucus epistom in the bronchial lumen and few infiltrations of
      inflammatory cells around the bronchi. CONCLUSION: The improvement of the simple
      acupoint catgut embedding at "Feishu" (BL 13), "Danzhong" (CV 17)and "Shenshu"
      (BL 23) on the airway inflammation in asthmatic rats is better than that of
      catgut embedding at "Feishu" (BL 13) and "Danzhong" (CV 17) or at "Shenshu" (BL
      23) only.

PMID- 22997796
TI  - [Cupping at Shenque (CV 8) combined with embedding thread at Back-shu points for
      80 cases of chronic urticaria].

PMID- 22997797
TI  - [Multi-needling in rows acupuncture created by professor HAN Jing-xian].
AB  - The multi-needling in rows acupuncture is created by professor HAN Jing-xin, in
      which the cutaneous region, muscle region and meridian are involved in treatment
      in terms of the depth of disease and the location of treatment. The multi
      needling in rows acupuncture on the cutaneous region is for the disorders of the
      cutaneous superficial area, characterized as shallow puncturing to the skin
      layer. The multi-needling in rows acupuncture on the muscle region is for the
      disorders of the muscle region, characterized as needling the muscle regions with
      the multiple meridians involved, but without the meridian distributions
      concerned. The multi-needling in rows acupuncture on the meridian is used at the
      meridian points in terms of the meridian disorders and Zang fu disorders. The
      multi-needling in rows acupuncture for meridian disorders is applied to treat the
      local disorders on the running course of the meridian. The multi-needling in rows
      acupuncture for Zang fu disorders is used to treat the relevant Zang fu disorders
      in terms of the running course of the meridian, in which, the multi-needling in
      rows acupuncture at the Back-shu points is used specially for the disorders of
      the thoracic and abdominal organs and systems with the disturbance of the
      autonomic nerves included; the multi-needling in rows acupuncture at the three
      meridians in occipital region is specially for vertigo and ataxia induced by the
      cerebella disorders.

PMID- 22997798
TI  - [Discussion on clinical research thinking of insulin resistance and its related
      di-seases treated with acupuncture and moxibustion].
AB  - According to the analysis of current clinical research situation on insulin
      resistance and its related diseases: obesity, type 2 diabetes mellitus,
      hypertension, polycystic ovary syndrome (PCOS) treated with acupuncture and
      moxibustion, some clinical research thinking are proposed: based on national,
      international acupuncture-moxibustion standard, setting a normalized clinical
      research programme in accordance with the clinical practice; addressing effective
      acupoints combination and prescription, emphasizing the role played by vital qi
      strengthening in the treatment of insulin resistance and its related diseases;
      taking advantage of acupuncture and moxibustion in treatment apportunity, that is
      to say , mainly focus on prevention; setting proper control group, grasping the
      theoretical and clinical characteristics of acupuncture and moxibustion. In this
      way, some reference could be provided for insulin resistance and its related
      diseases treated with acupuncture and moxibustion.

PMID- 22997799
TI  - [Comparison and thinking on literatures of low back pain treated with acupuncture
      moxibustion published in foreign SCI journals and domestic core journals].
AB  - The literatures of clinical research on acupuncture treatment of low back pain
      included in foreign SCI journals as well as the domestic core journals in the
      recent 10 years were collected in this article to discuss the divergence of views
      domestically and abroad. The result showed that acute and chronic back pain and
      low back pain were generally set as the targets of research abroad. While,
      diseases with western diagnosis such as lumbar disc herniation was often set as
      the study target by domestic researchers. It indicats that divergence existed in
      understanding and study methods between Chinese and foreign research fellows.
      Thus, comparison should be carried out so as to learn from the strong points of
      each other and close the gap.

PMID- 22997800
TI  - [Function of the present systematic evaluation in establishment of guidance for
      clinical practice].
AB  - OBJECTIVE: Treatment of insomnia with acupuncture is taken as an example to
      explore the significance and problems existed in the present systematic
      evaluation in establishment of guidance for clinical practice. METHODS: Fifteen
      articles on systematic evaluation of both English and Chinese were retrieved and
      studied carefully, their basic information was analyzed. Through study on the
      establishing process of the guidance of clinical practice, researches were
      focused on the possible significance of the articles to the guidance as well as
      the notes in the reuse of those articles since problem still existed. RESULTS: It
      is held that the systematic evaluation has great significance on the
      establishment of the guidance from the aspects of applicable people, recommended
      standards of diagnosis and therapeutic evaluation, extended recommendation and
      methodology. Great importance should also be attached to the direct application
      of the research result and understanding of the evaluation result. The data
      should be rechecked when necessary. CONCLUSION: Great guiding function can be
      found on the systematic evaluation of articles to the guidance. Moreover, if
      information needed to be taken into a full play, specific analysis should also be
      done on the concrete research targets.

PMID- 22997801
TI  - [Academic features of CHEN Ying-long of the Chengjiang acupuncture school].
AB  - CHEN Ying-long is a famous acupuncturist in modern China. He is one of the
      disciples of CHENG Dan-an who is considered as the initiator of the Chengjiang
      acupuncture school. Through collecting and sorting of CHEN's theses and medical
      records which carried on and developed the Chengjiang acupuncture school, it is
      found that his academic features of acupuncture manifested in the following
      points: attaching importance on prac tice of qi and finger force; valuing the
      reinforcing and reducing manipulations according to midnight-noon and ebb-flow
      doctrine; utilizing moxibustion to treat difficult and complicated diseases;
      applied group points to treat chronic diseases; good at treating manic type of
      mental disorder with deep acupuncture at Fengfu (GV 16).

PMID- 22997802
TI  - [Discussion on operating technique of ancient moxibustion].
AB  - To summarize and discuss the operating technique of ancient moxibustion with the
      consulting of some relevant literatures. In the ancient, the dosage of the
      moxibustion was based on the size and the number of moxa cones, the feelings of
      patients and their reaction after the treatment. Of them, the size and the number
      of moxa cones were estimated by doctors own experience, and it would be more
      objective and suitable for patients' needs if the dose was additionally decided
      on the reactions of patients (pain, post-moxibustion sore, sweating, spots and so
      on). It could have significance for improving clinical effects if attention is
      paid to the feelings and reactions of patients, the size and the number of moxa
      cones and the time of moxibustion.

PMID- 22997803
TI  - [Analysis on the characteristics and interference factors of different types of
      measurement instruments for meridian-acupoint resistance].
AB  - The meridian-acupoint has response function and effect function. As a direct
      reflection between acupoint and diseased area, the response function is the
      foundation of the effect function, and skin resistance of acupoint is usually
      used as an objective indice for research of meridian-acupoint response. Among the
      skin resistance-based researches on specificity of meridian-acupoint reaction,
      the selection of instrument is a key point. At present the main measurement
      instruments for meridian-acupoint resistance include dual-electrode device and
      four-electrode device. After analyzing the characteristics and inter-ference
      factors of different types of measurement instruments for meridian-acupoint
      resistance, dual-electrode device is suitable for qualitative analysis, for its
      control of interference factors needs to improve. The four-electrode device is
      good at quantitative research, for it is easier to control interference factors.
      Yet, there is more for research department to do to improve the instrument design
      by modern scientific technique in order to meet need for research.

PMID- 22997804
TI  - [Application of multi-function moxibustion couch and its developing
      significance].
AB  - The basic structure and application manipulations of the multi-function
      moxibustion couch are introduced in this article. The designation of the couch is
      reasonable and its structure is simple. With easy manipulations and simple
      application, fumigation and moxibustion therapy is fulfilled by the moxa roll
      ignited under the couch. It has the characteristics of heat and medicine
      concentrating with strong penetration and extensive application area. And it can
      be applied especially on pain of the neck, shoulder, low back and leg, diseases
      of stomach and intestines, complicated gynaecological diseases as well as on
      health keeping.

PMID- 22997805
TI  - [Pricking and cupping in vernal equinox for preventing common cold].

PMID- 22997806
TI  - [Survey of studies on drug abstinence with acupuncture in recent 10 years].
AB  - The effect of acupuncture on substance withdrawl syndromes and craving relapse
      prevention of the recent 10 years were reviewed as well as its mechanism. The
      therapeutic effect and the possible mechanism were analyzed on the basis. From
      the three aspects of anti protracted abstinence symptoms, craving relapse
      prevention and mechanism of acupuncture, the development tendency and the
      prospect of application on drug withdrawl with acupuncture were expected. And it
      is proposed that clinical observation of acupuncture intervention on craving
      should be developed, the mechanism of acupuncture impact on cognitive behavior,
      blocking study and memory processing related to drug addiction should be
      explored, so as to further give play to the advantages of acupuncture on anti
      drug addiction.

PMID- 22997807
TI  - [Effect and mechanism of traditional Chinese medicine and their active
      constituents in postmenopausal osteoporosis].
AB  - Postmenopausal osteoporosis is one of the commonest systemic bone metabolism
      diseases among menopausal women, mainly caused by lowering internal estrogen.
      Although Hormone Replacement Therapy (HRT) is an effective method in clinical
      practice for years, it shows side-effect in increasing gynecological carcinoma.
      It has already been proved by clinical tests that multiple traditional Chinese
      medicine formulas and their monomer ingredients and phytoestrogen-like active
      constituents contained in traditional Chinese medicines are effective on treating
      osteoporosis with relatively less side-effects comparing with HRT. They show
      protective and therapeutic effects by acting on estrogen receptors of targeted
      tissues and targeted cells and then affecting expressions of bone metabolism
      related regulatory proteins and factors in downstream signal conduct paths.
      Recent studies on estrogen related receptor (ERR) provide new possibilities and
      pathways for mechanism of traditional Chinese medicine and their active
      constituents in osteoporosis.

PMID- 22997808
TI  - [Regulatory mechanism of p38MAPK signaling pathway on renal tissue inflammation
      in chronic kidney disease and interventional effect of traditional Chinese
      medicine].
AB  - The inflammatory reaction of renal tissues and its relevant tissue damages (such
      as glomerulosclerosis and renal interstitial fibrosis) are important factors for
      the development of chronic kidney diseases (CKD) to end-state renal diseases. Of
      them, p38 mitogen-activated protein kinase (MAPK) signaling pathway plays an
      important role in regulating expression and bioactivity of multiple nuclear
      transcription factors, impacting synthesis of downstream inflammatory mediators
      and activating inflammatory cells. Some monomer traditional Chinese medicines and
      their extracts (such as emodin and berberine) and some traditional Chinese
      medicine compound prescriptions (such as Yishen Huoxue decoction) can affect
      inflammatory reaction of renal tissues by regulating p38MAPK signaling pathway,
      thas improving reduce glomerulus and renal interstitial inflammatory injury.

PMID- 22997809
TI  - [Western and traditional Chinese medicine disease management programs of chronic
      heart failure].
AB  - Chronic heart failure (CHF) is one of the greatest disease in modem medicine as
      chronic disease . It cost lots of financial resources to deal with. Western and
      traditional Chinese medicine Disease management programs (DMP) can notability
      improve the qualities of life and reduce the expenses for CHF. The disease
      management programs of CHF have achieved kind of success, but the management
      programs method witch is of traditional Chinese medicine (TCM) characteristic
      idea carry into testing execution in few TCM hospitals only. This article review
      the necessary of DMP research, advances in research of DMP research, and
      relationship between management programs method of Western and traditional
      Chinese medicine and illness state improvement of CHF patients.

PMID- 22997810
TI  - [Fluid suspension co-culture of Dendrobium officinale protocorm and living
      fungus].
AB  - OBJECTIVE: To set up a system for fluid suspension co-culture of Dendrobium
      officinale protocorm and living fungus MF24, so as to provide certain scientific
      evidence for industrial production of protocorm. METHOD: Whether the protocorm
      culture system was suitable for the normal growth of MF24 fungus were studied,
      the growth of protocorm cultured alone and co-cultured with the fungus were
      researched under light and dark culture conditions, the biomass and proliferation
      times were determined, and HPLC method was used to analyze and compare the
      changes of 11 characteristic peak areas in D. officinale protocorm. RESULT: The
      MF24 fungus could grow normally in the 6,7-V liquid medium used to culture the
      protocorm, and when it was cultured by 8-10 hours per day under 1 500 lx, the
      growth rate of the fungus was slowed. Protocorm could grow normally in light and
      dark culture conditions, and add the MF24 fungus in the early cultivation stages
      of protocorm, both inhibit the growth of each other. In the protocorm for the
      growth stability to add 5 diameter 9 mm fungi block, the protocorm growth and
      chemical composition type had no significant effect. However, under illumination,
      co-cultured for 5 days protocorm of which 10 compounds content decreased 13.64%
      to 138.47%, in dark conditions, co-cultured for 5 days protocorm of which 7
      compounds increased by 0.71% to 12.82%, and 4 compounds slightly reduced by 3.03%
      to 14. 14% compared with the control. CONCLUSION: Under the appropriate
      condition, living fungus MF24 could co-culture with the D. officinale protocorm,
      and affected the latter's secondary metabolite levels.

PMID- 22997811
TI  - [Cloning and bioinformatics analysis of cycloartenol synthase (HcCAS1) gene in
      Huperzia carinata].
AB  - OBJECTIVE: To clone and sequence the open reading frame of cycloartenol synthase
      (CAS) from Huperzia carinata. METHOD: After searching the transcriptome dataset
      of H. carinata, one unique sequence containing oxide squalene cyclases domain was
      discovered. The primers were designed according to the cDNA sequence of CAS from
      the dataset. And then, the open reading frame of CAS was cloned by RT-PCR
      strategy with the template of mixed RNA extracted from root, stem and leaf of H.
      carinata. The bioinformatic analysis of this gene and its corresponding protein
      was performed. RESULT: One unique sequence of CAS, named as HcCAS1 (GenBank
      accession number JN790125) , was cloned from H. carinata. The open reading frame
      of HcCAS1 consists of 2 474 bp, encoding one polypeptide with 757 amino acids.
      CONCLUSION: This study cloned and analyzed CAS from H. carinata for the first
      time. The result will provide a foundation for exploring the mechanism of sterol
      biosynthesis in Huperziaceae plants.

PMID- 22997812
TI  - [Molecular cloning of farnesyl diphosphate synthase from Eleutherococcus
      senticosus and its bioinformatics and expression analysis].
AB  - OBJECTIVE: To clone farnesyl diphosphate synthase (FPS) gene from Eleutherococcus
      senticosus and analyze the bioinformatics and expression of the gene. METHOD: The
      FPS full length cDNA was cloned by rapid amplification of cDNA ends (RACE). The
      data was analyzed by bioinformatics method, the structure and function of FPS was
      deduced. The expression of FPS in different organ of E. senticosus was detected
      by RT-PCR. RESULT: The full length of FPS cDNA was 1 499 bp containing a 1 029 bp
      ORF that encoded 342 amino acids. The deduced protein sequence exhibited two Asp
      riches conserved motifs (DDXXD). Without transmembrane domain, FPS was located in
      cytoplasm. RT-PCR result showed that FPS gene expressed in different organs of E.
      senticosus. The expression amounts of FPS in different organs were different
      significantly (P < 0.05). CONCLUSION: The FPS gene of E. senticosus was
      successfully cloned for the first time, and provided a stable foundation for
      studying on its effect and expression control on E. senticosus saponins
      biosynthesis.

PMID- 22997813
TI  - [EMS mutation of suspension cells and selection of high temperature tolerant
      mutants from Pinellia ternata].
AB  - OBJECTIVE: To determine the optimal concentration and processing time of EMS
      mutation for suspension cells from Pinellia ternata. METHOD: Under four EMS
      concentration gradients (0.1% , 0.2%, 0.4%, 0.6%) and three processing time
      gradients (0.5, 1.0, 2.0 h), the suspension cells of P. ternata were mutagenized.
      RESULT AND CONCLUSION: The results showed that the survival rate was
      significantly different under the different concentrations of EMS and the
      different processing time. In the same processing time, the EMS concentrations
      were increased, but the suspension cells survival rate decreased gradually. The
      optimum EMS concentration for the mutagenesis was 0.4% and the best processing
      time was 1 hour.

PMID- 22997814
TI  - [Primary investigation of contaminating fungi on Panax notoginseng and Amomum
      tsaoko in Yunnan].
AB  - OBJECTIVE: To analyze the potential risks of fungal contaminants on Panax
      notoginseng and Amomum tsaoko. METHOD: The primary investigation was conducted in
      the P. notoginseng and A. tsaoko major production areas in Yunnan. Samples of P.
      notoginseng and A. tsaoko were collected from drugstores and markets in 3 cities
      of Yunnan. Dilution-plate method was applied for the isolation of fungi, the
      obtained species were identified according to morphological and molecular
      approaches. RESULT: Paecilomyces lilacinus and Penicillium citrinum were dominant
      on samples of Panax notoginseng. P. lilacinus and Aspergillus flavus were
      dominant on samples of Amomum tsaoko. CONCLUSION: In Yunnan province, the major
      fungal contaminants on P. notoginseng are P. lilacinus and P. citrinum and the
      major fungal contaminants on A. tsaoko are P. lilacinus and Aspergillus flavus.
      There exists a potential contamination risk of citrinin on P. notoginseng and
      aflatoxin on A. tsaoko.

PMID- 22997815
TI  - [Ri plasmid transformation and metabolism of ginseng products on HepG2 cells].
AB  - OBJECTIVE: To study the Ri plasmid transformation and metabolism of ginseng
      products on HepG2 cells. METHOD: The inhibitory effect of ginseng saponin on
      hepatoma HepG2 cells was studied. The hairy root-induced conditions were screened
      by orthogonal experimental design. The culture conditions were determined through
      hairy root biomass accumulation and saponin content. The effect of ginsenoside on
      HepG2 cells was determined by MTT assay. RESULT AND CONCLUSION: The optimal
      ginseng hairy root inducing conditions: A = 0.6, infection time of 10 min, pre
      incubation time for the 3 d. The best culture conditions: MS medium, pH 6.1, 24
      degrees C. At those conditions the hairy root bio-accumulation and saponin
      content were higher. The results of ginseng saponins on the inhibitory effect of
      HepG2 cells showed that inhibition of ginseng saponins on HepG2 was the
      concentration positively related.

PMID- 22997816
TI  - [Quality classification criteria of Oldenlandia diffusa seeds].
AB  - OBJECTIVE: To establish the quality classification criteria of Oldenlandia
      diffusa seeds. METHOD: Thirty batches of O. diffusa seeds from different
      provenances with different collecting time were selected. And the seed
      germination percentage, seed purity, weight per 1 000 grains, moisture content
      and seed viability were determined and analyzed through SPSS 11.0 software.
      RESULT AND CONCLUSION: Seed germination percentage was selected as the main index
      for classification, while seed purity, weight per 1 000 grains and moisture
      content could be used as references. The quality classification criteria of O.
      diffusa seeds have been initially established.

PMID- 22997817
TI  - [Tissue distribution of ginsenoside Rg1 before and after modification by PEG].
AB  - OBJECTIVE: To investigate targeted distribution of ginsenoside Rg1 in mice
      tissues before and after modification by the PEG. METHOD: SD mice were randomly
      divided into two groups and given Rg1 and PEG-Rg1 by intravenous injection
      respectively. Their samples of blood and organ tissues were taken at different
      time points. The content of Rg1 in samples were determined by UPLC and used as
      indicator to observe the targeted distribution of Rg1 in mice tissues. RESULT:
      The AUC of ginsenoside Rg1 in tissues of the Rg1 group were in the order of
      liver, kidney, lung, heart and spleen, with the liver targeting coefficient was
      of 2.01. While the AUC of ginsenoside Rg1 in tissues of the PEG-modified group
      were in the order of the kidney, liver, lung, heart, spleen, with the liver
      targeting coefficient was of 9.21. CONCLUSION: PEG modified Rg1 can increase
      Rg1's targeting selectivity to the liver, kidney and lung in mice.

PMID- 22997818
TI  - [Impact of sample data repeatability on NIR calibration model].
AB  - OBJECTIVE: To investigate the impact of repeated data acquisition on the
      stability of NIR quantitative calibration model, and make a preliminary analysis
      on reasons for the impact. METHOD: Yinhuang decoction was used as the subject,
      and NIR spectrum samples were collected. By reference to HPLC's determination
      value, the baicalin quantitative calibration model was established by using
      recursive least square algorithm to detect cumulative-LVs curve of latent
      variables. The impact of calibration model caused by repetitive samples was
      explained in latent variance space. RESULT: After averaging the repetitive
      spectrum samples, quantitative prediction model, which was built by optimal
      method of spectrum pretreatment, showed the ideal prediction result (RMSECV =
      1.824). The area under the cumulative-LVs curve of latent variables was obviously
      larger than other modeling methods, i. e., this model is more stable. CONCLUSION:
      Averaging of multiple measurements can dramatically improve the predictive
      ability of the model and make the model more stable.

PMID- 22997819
TI  - [Comparison of transformation of four processed rhubarb aqueous extracts in
      intestinal bacteria in vitro].
AB  - OBJECTIVE: To compare the metabolic transformation of four processed rhubarb
      aqueous extracts in rat intestinal bacteria in vitro. METHOD: Rat intestinal
      bacteria test solution and each of four processed rhubarb aqueous extracts were
      incubated under anaerobic conditions at 37 degrees C. High-performance liquid
      chromatography with diode-array detection (HPLC-DAD) and tandem mass spectrometry
      (HPLC-MS/MS) was used for the qualitative analysis on the components that can be
      bio-transformed by rat intestinal bacteria as well as the trend of metabolic
      transformation of each parent compounds according to the changes in
      chromatographic peak areas in different incubation times. RESULT: Anthraquinones,
      glucose gallates and naphthalenes glucosides could be bio-transformed by rat
      intestinal bacteria. Of them, anthraquinones were undoubtedly the most prevalent
      parent compounds, as 12 out of the 17 metabolites were tentatively assigned as
      metabolites transformed from anthraquinones. Besides, it was also found that each
      parent compound in four processed rhubarb extract were diverse from each other
      with the incubation time. CONCLUSION: The preparations change composition and
      proportional relationship of ingredients contained in rhubarb and thus impacting
      their transformation effect in intestinal bacteria.

PMID- 22997820
TI  - [Pharmacokinetics of Danshen multi-component osmotic pump tablets in Beagle
      dogs].
AB  - OBJECTIVE: To study the variation in plasma concentration after oral
      administration of Danshen multi-component osmotic pump tablets in Beagle dogs
      with conventional Danshen tablets as the control preparation, in order to assess
      the sustained release of Danshen multi-component osmotic pump tablets. METHOD:
      HPLC was adopted for determination, with Shimadzu's ODS-SP column (4.6 mm x 150
      mm, 5 microm), flow rate of 1 mL x min(-1), and column temperature of 30 degrees
      C. Protein in plasma samples of tanshinone II(A) and salvianolic acid B was
      removed by ethyl acetate extract and acetone precipitation method respectively.
      Their pharmacokinetic parameters were calculated based on determination results.
      RESULT: The methodology study on the two constituents with different polarity
      showed conformity to the requirements. Compared with conventional Danshen
      tablets, Danshen multi-component osmotic pump tablets showed decrease in Cmax and
      extension in Tmax after oral administration in Beagle dogs. CONCLUSION: Danshen
      multi-component osmotic pump tablet has a good sustained-release effect compared
      with conventional Danshen tablets.

PMID- 22997821
TI  - [Identification technique for in vivo ingredients of traditional Chinese
      medicines based on LC-MS analysis].
AB  - Serum pharmacochemistry of traditional Chinese medicine (TCM) is a direct and
      effective method for determining efficacious substance foundation of TCM.
      However, the complexity of chemical constituents of TCM and the interaction among
      ingredients in the in vitro process make the analysis on in vitro ingredients of
      TCM arduous. Liquid chromatography coupled with tandem mass spectrometry (LC
      MS/MS) has become the cornerstone in detection and characterization of in vivo
      ingredients of TCM because of its sensitivity and ability to analyze complex
      mixtures. However, due to significant interference from endogenous species,
      detection and identification of the constituents of TCM in the biological
      matrices are often difficult. There is a crying need for introducing specialized
      ingredient identification techniques to avoid artificial omission of in vivo
      ingredients of TCM. On the basis of the analysis on transitional ingredients in
      rat blood, this essay introduces the application of such pattern recognition
      methods as mass defect filter, Metabolynx software and principal component
      analysis, partial least squared discriminant analysis and orthogonal partial
      least squared discriminant analysis in identifying in vivo ingredients of TCM.

PMID- 22997822
TI  - [Separation of choline from Coptidis Rhizoma and impact on glucose metabolism of
      berberine in HepG2 cells].
AB  - OBJECTIVE: To investigate action of hydrophilic constituents from Coptidis
      Rhizoma on glucose-lowering effect metabolism of berberine in HepG2 cells.
      METHOD: Hydrophilic fractions of Coptidis Rhizoma were prepared by high speed
      counter current chromatography and separated by silica gel column chromatography.
      MTT assay was used to monitor the proliferation of HepG2 cells, and Kit was used
      to test the glucose consumption in culture solution. RESULT: Choline was
      separated from Coptidis Rhizoma for the first time. Cell assay showed choline can
      significantly increase the glucose lowering effect of berberine and improve the
      cytotoxicity of berberine within test concentration. Compared with same dose of
      berberine, berberine 38 mg x L(-1) in combination with choline 100 mg x L(-1) can
      make glucose consumption increase by 34% and elevate cell livability up to 75% in
      HepG2 cells. CONCLUSION: The results suggest that choline had a synergistic
      effect on improving glucose absorption of berberine and decreasing cytotoxicity
      of berberine.

PMID- 22997823
TI  - [Chemical constituents from aqueous extract of Gastrodia elata].
AB  - Two new compounds (1 and 2), together with twenty-one known compounds (3-23),
      were isolated by a combination of various chromatographic techniques including
      column chromatography over macroporous resin, MCI gel, silica gel, and Sephadex
      LH-20 and reversed-phase HPLC. Their structures were identified by spectroscopic
      data analysis as 4-hydroxy-3-(4-hydroxybenzyl) benzyl methyl ether (1), 4-(
      methoxymethyl) phenyl-1-O-beta-D-glucopyranoside (2), hibicutaiwanin (3), 4-(4
      hydroxybenzyl)-2-methoxyphenol (4), 4,4'-methylenebis(2-methoxyphenol) (5), L
      phenyllactic acid (6) ,4-hydroxy-3-methoxybenzyl ethol ether (7), p
      hydroxylbenzyl alcohol (8), p-hydroxylbenzyl methyl ether (9), p-hydroxylbenzyl
      ethyl ether (10), p-hydroxybenzaldehyde (11), p-hydroxybenzoic acid (12), p
      hydroxybenzoic acid (13), gastrodin (14), 4-(ethoxymethyl) phenyl-1-O-beta-D
      glucopyranoside (15), 4-(beta-D-glucopyranosyloxy) benzaldehyde (16), p
      methylphenyl-1-O-beta-D-glucopyranoside (17 ), methyl-O-beta-D-glucopyranoside
      (18), 5-hydroxymethl-furan aldehyde (19), parishin (20), parishin B (21),
      parishin C (22), and diosgenin (23). The 13C-NMR data of compound 4 was first
      reported.

PMID- 22997824
TI  - [Phenolic components from Petasites tricholobus].
AB  - OBJECTIVE: To study the anti-inflammatory and antioxidant effects of Petasites
      tricholobus and its phenolic components. METHOD: Phenolic compounds were
      separated purified by column chromatographic methods such as macroporous resin D
      101, silica gel, ODS, MCI GEL CHP 20P, Sephadex LH-20. Their structures were
      identified on the basis of physicochemical property and multiple spectral data.
      RESULT: Nineteen phenolic compounds were separated from 95% ethanol extracts from
      P. tricholobus Franch. and identified as sulfonated benzyl glucoside (1), 3
      (4beta-D-glucopyranosyloxy-3, 5-dimethoxy) -phenyl-2E-propenol (2),
      dihydrosyringin (3), tangshenosides II (4), 4-hydroxy-2,6-dimethoxyphenol-1-O
      beta-D-glucopyranoside (5), 4-hydroxymethyl-2, 6-dimethoxyphenyl-1-O-beta-D
      glucopyranoside (6), arbutin (7), rutin (8), kaempferol-3-O-alpha-L
      rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranoside (9), quercetin-3-O-beta-D
      glucopyranoside (10), kaempferol-3-O-beta-D-glucopyranoside (11), afzelin (12),
      petasiphenol (13), caffeic acid (14), chlorogenic acid (15), 2-hydroxy-5
      acetylbenzoic acid (16), p-hydroxy-benzoic acid (17), protocatechuic aldehyde
      (18) , and p-hydroxy-phenylpropionic acid (19). CONCLUSION: Above result shows
      that phenolic compounds contained in P. tricholobus mainly include simple
      phenols, phenolic glycosides, coffee acid and flavonoid glycosides. Among them,
      compound 1 was separated from the composite family for the first time; compounds
      2-7, 9, 11, 12, 16, 19 were separated from the genus Petasites for the first
      time, and the others were separated from the plant for the first time. These
      compounds have been proved to have pharmacological effects such as anti
      inflammation, antibiosis, antioxidantion.

PMID- 22997825
TI  - [Chemical constituents contained in Desmodium caudatum].
AB  - OBJECTIVE: To study chemical constituents contained in Desmodium caudatum.
      METHOD: The chemical compounds were separated by using such chromatographic
      methods as macroporous resin, Sephadex LH-20, ODS and normal phase silicagel
      column, and their structures were identified by spectroscopic data analysis.
      RESULT: Fifteen compounds were separated and identified as stigmasterol (1), beta
      sitosterol (2), citrusinol (3), hibiscone A (4), yukovanol (5), kenusanone I (6),
      neophellamuretin (7), desmodol (8), erythrotriol (9), hibiscone D (10),
      kaempferol (11), 8-prenylquercetin (12), leachianone G (13), 5,7,4'-trihydroxy
      dihydroflavonol (14), and 4H-1-benzopyran-4-one, 2-(3,4-dihydroxyphenyl) -2, 3
      dihydro-3,5,7-trihydroxy-8-( 3-methyl-2-butenyl) -, (2R-trans)-(9CI) (15).
      CONCLUSION: All of the compounds were separated from D. caudatum for the first
      time except compound 8.

PMID- 22997826
TI  - [Difference of chemical constituents contained in Tibetan herb Jiadiranguo from
      different habitats by HPLC fingerprint].
AB  - OBJECTIVE: To establish the HPLC fingerprint for Halenia elliptica herbs, a
      traditional Tibetan medicine, in order to study constituents contained in H.
      elliptica from different habitats and compare their differences. METHOD: HPLC
      analysis was made on a Welchrom-C18 (4.6 mm x 250 mm, 5 microm) with water and
      acetonitrile as mobile phase. The wavelength was detected as 265 nm, the flow
      rate was 1.0 mL x min(-1), and the column temperature was 40 degrees C. The
      software for chromatographic fingerprint was applied to analyze the similarity.
      And principal component analysis was conducted. RESULT: Twelve common
      chromatographic peaks were identified by fingerprint, showing a low similarity in
      constituent and variety. The significant difference in the proportion between
      xanthones and aglycones in each batch of herbs indicated no notable correlation
      between constituent characteristics and geographic locations of habitats.
      CONCLUSION: The method is so simple, exclusive, stable and highly repeatable that
      it can provide reference for identification and quality assessment of H.
      elliptica herbs.

PMID- 22997827
TI  - [Study on molecular characteristics of four components contained in Hedysari
      Radix polysaccharide by gel permeation chromatography-multiangle laser light
      scattering technology (GPC-MALLS)].
AB  - OBJECTIVE: To determine such molecular characteristic parameters as absolute
      molecular weight, molecular weight distribution, root-mean-square turning radius
      (Rg) and polydispersity index (Mw/Mn) of four components contained in Hedysari
      Radix polysaccharide 3 (HPS-3) and map weight-average molecular weight (Mw) with
      root-mean-square turning radius (Rg), in order to calculate conformations of the
      four components at solution state. METHOD: The gel permeation chromatography
      multi angle laser light scatting (GPC-MALLS) was adopted, with 0.1 mol x L(-1)
      NaNO3 contained 0.02% NaN3 as the mobilephase, Ultrahydrogel 1000 connected in
      series with Ultrahydrogel500. RESULT: Among the four components of HPS-3, HPS-3-C
      showed the highest weight average molecular weight of 1.986 x 10(5) g x mol(-1),
      followed by HPS-3-B 1.113 x 10(5) g x mol(-1) and HPS-3-D 8.457 x 10(4) g x mol(
      1) HPS-3-A showed the lowest weight average molecular weight of 1. 223 x 10(4) g
      x mol(-1) but the highest square radius of gyration, that is 55.5 nm. HPS-3-D had
      the widest range of molecular weight distribution in four components, with the
      polydispersity index (Mw/Mn) of 2.543. In the mobile phase, HPS-3-A was globular
      structure, HPS-3-C was random coil, HPS-3-B and HPS-3-D were both highly branched
      structure. CONCLUSION: The results provided necessary basis for further studies
      on molecular characteristics of the four components contained in HPS-3 and their
      relationship with bioactivity.

PMID- 22997828
TI  - [Comparison of effect of formulas clearing away heat and promoting blood
      circulation on prevention and treatment of liver fibrosis in CCl4 mice].
AB  - OBJECTIVE: To observe the effect of traditional Chinese medicine formulas
      clearing away heat and promoting blood circulation-Biejiayinzi (BJYZ), Gexiazhuyu
      Tang (GXZYT) and Fugan Wan (FGW) on liver fibrosis in CCl4 mice by screening and
      analyzing formula-syndrome database of kidney and liver fibrosis based on the
      principle of formula-syndrome, compared with pivot-harmonizing decoction. METHOD:
      Ten-week-old male C57BL/6 mice, with the weight of (20 +/- 3) g, were randomly
      divided into 6 groups: the normal group, the model group, the BJYZ group, the
      GXZY group, the FGW group and the XST group. Except the normal group, other
      groups were abdominally injected with 10% CCl4 olive oil solution a dose of 2 mL
      x kg(-1) body weight for four weeks, three times each week. Meanwhile, the latter
      four groups were administered with extracts of BJYZ, GXZYT, FGW and XST,
      respectively, once every day, concomitantly continued CCl4 administration. The
      normal and the model groups were given the same volume of deionized water. The
      levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      gamma-glutamyl transpeptidase (gamma-GT), Alb and TBil were detected by
      chemiluminescence. The hydroxyproline (HYP) content was detected by acid
      hydrolysis method. The hepatic collagen deposition was evaluated with Sirius red
      staining. RESULT: Compared with the normal group, the model group recorded
      notable decrease in weight and increase in the ratio of liver weight and body
      weight and the ratio of spleen weight and body weight, with obvious fatty
      degeneration and inflammatory necrosis in liver cells. Collagen fiber deposition
      was so notable to form fibrous septums and pseudolobules. The levels of serum
      ALT, AST, TBil, gamma-GT, the HYP content in liver tissue and the deposition of
      hepatic collagen were significantly increased in the model group. Compared with
      model group, Serum AST were significantly decreased in BJYZ group as gamma-GT
      decreased in the GXZYT group, without notable decrease in degeneration and
      inflammatory necrosis in liver cells and collagen deposition. The GXZYT group
      showed significant decrease in gamma-GT, with slight improvement in degeneration
      and inflammatory necrosis in liver cells and reduction in collagen deposition.
      The ratio of liver weight and body weight, AST, gamma-GT and HYP content were
      significantly decreased in the FGW group, with slight improvement in degeneration
      and inflammatory necrosis in liver cells and reduction in collagen deposition.
      The XST group showed decrease in the ratio of liver weight and body weight, with
      no obvious change in inflammation and fibrosis of hepatic tissue. CONCLUSION: FGW
      shows the best effect of prevention and treatment of liver fibrosis in CCl4 mice.

PMID- 22997829
TI  - [Protective effect of atractylenolide I on immunological liver injury].
AB  - OBJECTIVE: To study the protective effect of atractylenolide I on immunological
      liver injury induced by BCG and LPS. METHOD: Kunming mice were randomly divided
      into 6 groups: the normal group, the model group, positive control biphenyl
      group, the atractylenolide I high does group, the atractylenolide I middle dose
      group and the atractylenolide I low dose group (60, 120, 240 mg x kg(-1)), with
      12 mice in each group. Immunological liver injury in mice was induced by BCG and
      LPS to compared liver index and spleen index and detect content of serum ALT,
      AST, MDA and GSH-px in serum and NO, iNOS, TNF-alpha in serum and liver
      homogenate. Liver pathological changes were observed by HE staining. RESULT: Both
      of atractylenolide I and biphenyl remarkably decrease the increased live index
      and spleen index (P < 0.05), improve the histopathological changes in liver and
      pathological grades of liver tissues and relieve the inflammatory reaction
      induced by BCG and LPS. They showed a notable effect in improving MDA and GSH-px
      in serum. CONCLUSION: Atractylenolide I can obviously protect immunological
      injury liver a dose-dependent manner within the range of test doses. Its
      mechanism may be related to release or over expression of inhibitory inflammatory
      medium such as NO, iNOS and TNF-alpha.

PMID- 22997830
TI  - [Study on protective mechanism of kushenin injection on colonic mucosa of
      experimental colitis rats].
AB  - OBJECTIVE: To study the effect of NOD2 on colitis pathogenesis in experimental
      rats, and discuss therapeutical effect and mechanism of kushenin injection (OMT)
      on colitis in experimental rats. METHOD: Fourty Sprague-Dawley (SD) rats were
      randomly divided into four groups: the normal control group, the model group, the
      SASP group, and the OMT group, with 10 rats in each group. Except the normal
      control group, models were established in the remaining three groups with TNBS.
      The OMT group was injected with kushenin injection, the SASP group was orally
      administered with mesalazine suspension, the model group and the normal group
      were orally administered with distilled water for 15 days. Colon lesion score and
      histological score of experimental rats were observed. Expression of NOD2, NF
      kappaB p65 protein in rats colonic mucous was detected by immunohistochemistry.
      Expression of IL-6 in rat colon mucous was detected by ELISA. RESULT: Compared
      with normal control group, the expression of NOD2, NF-kappaB p65 and IL-6 in
      colonic mucosa of the model group were significantly increased (P < 0.01). The
      SASP group and the OMT group showed lower expressions of NOD2, NF-kappaB p65 and
      IL-6 in colonic mucosa than the model group (P < 0.01, P < 0.05). CONCLUSION: The
      over expression of colonic mucosa proteins NOD2 and NF-kappaB p65 and increasing
      secretion of IL-6 take part in the appearance and development of ulcerative
      colitis. OMT can attenuate ulcerative colitis and protect colonic mucosa by
      inhibiting expression of NOD2, NF-kappaB p65 and decreasing IL-6.

PMID- 22997831
TI  - [Effect of curcumin on synapse-related protein expression of APP/PS1 double
      transgenic mice].
AB  - OBJECTIVE: To observe the effect of curcumin on the expression of synapse-related
      proteins PSD-95 and Shank1 in APP/PS1 double transgenic mice. METHOD: Three-month
      old APP/PS1 dtg mice were randomly divided into the model group, the positive
      Rosiglitazone control group and curcumin high (400 mg x kg(-1) x d(-1)), medium
      (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dose groups, with non
      genetically modified mice with the same background as the normal group. After the
      oral administration for three months, immunohistochemistry and Western blot were
      adopted for detection. RESULT: According to the behavioral detection, the
      treatment group and the model group showed differences in the place navigation
      test and the spatial probe test to varying degrees (P < 0.01 or P < 0.05). The
      expression of PSD-95 and Shank1-positive cells of hippocampus CA1 region
      significantly decreased in model mice compared with normal control group (P <
      0.01); while the curcumin intervention group showed recovery to some extend.
      Western blot results showed that the strap of PSD-95 protein expression became
      significantly thinner and lighter in the model group compared with the normal
      control group (P < 0.01); while the curcumin intervention group showed notably
      thicker and darker straps of PSD-95 protein expression (P < 0.05). CONCLUSION:
      Curcumin can increase the expression of synapse-related proteins PSD95 and Shank1
      in APP/PS1 double transgenic mice, improve structure and plasticity of synapse in
      APP/PS1 double transgenic mice and enhance their learning and memory abilities.

PMID- 22997832
TI  - [Effect and mechanism of curcumol on angiogenesis activity of zebrafishes].
AB  - OBJECTIVE: To conduct a preliminary study on the effect of curcumol in promoting
      angiogenesis activity and its mechanism in zebrafishes, in order to provide basis
      for clinical prescription. METHOD: Zebrafishes biological model was established
      to, observe curcumol's effect on embryo blood vessel growth, blood vessel
      regeneration of adult fishes after tail-cutting and tissue regeneration of fish
      fries after tail-cutting. The relative fluorescence quantitative PCR method was
      adopted to determine the gene expression of vascular endothelial growth factor
      (VEGFA) and receptor VEGFR2 of fish fries after tail-cutting. RESULT: Curcumol
      contributed to angiogenesis of intersegmental blood vessels in zebrafishes
      embryos and speed up regeneration of blood vessels in adult fishes after tail
      cutting. Furthermore, curcumol can increase the gene expression of VEGFA and
      VEGFR2 in fish fries. CONCLUSION: Curcumol can promote angiogenesis in
      zebrafishes, and enhance the gene expression of VEGFA and VEGFR2 in fish fries
      after tail-cutting and speed up the regeneration of their tails.

PMID- 22997833
TI  - [Study on compatibility of traditional Chinese medicine active constituents with
      antioxidant activity].
AB  - OBJECTIVE: To find a research method suitable to multi-component multi-index
      composition-activity relationship of traditional Chinese medicines (TCMs) with
      the antioxidant activity of four compatible active constituents of TCMs as the
      subject. METHOD: LARS-based regression algorithm and comprehensive weight
      coefficient method were adopted to study in vitro clearance of DPPH and
      polyaromatic hydrocarbon with different doses of four compatible active
      constituents--total flavonoids of Glycyrrhizae Radix et Rhizoma (TFG), Ginkgo
      Folium extract (GBE), total flavonoids of Epimedii Folium (TFE) and astragaloside
      (AST) according to the comprehensive efficacy assessment procedures, that is test
      design, efficacy test and mathematical modeling (model verification). RESULT:
      LARS and comprehensive weight coefficient method was adopted to assess the
      optimal comprehensive efficacy of clearing DPPH and polyaromatic hydrocarbon. The
      results showed that the optimal dose combination of compatible constituents is
      TFG-GBE-TFE-AST 1: 0.2545: 0.007 6:0.011 5. CONCLUSION: The above compatibility
      of TCMs constituents can effectively clear polyaromatic hydrocarbon and DPPH with
      a good antioxidation. The uniform design adopted in this experiment, in
      combination of synthetic weight method, is suitable to the data analysis of "non
      linear and small-sample" biotic experiment and the study on screening and
      assessment of compatibility of TCMs constituents.

PMID- 22997834
TI  - [Damage effect of Polygonum multiflorum fractions on human normal liver cells L02
      and liver cancer cells HepG2].
AB  - OBJECTIVE: To investigate the damage effect of different fractions from Polygonum
      multiflorum on normal human liver and liver cancer cells, in order to seek for
      fractions that can obviously kill cancer cells but have less impact on normal
      liver cells, and make a preliminary study on different mechanism of the two kinds
      of cells. METHOD: P. multiflorum water-eluted fraction (RW), 50% ethanol-eluted
      fraction (R50) and 95% ethanol-eluted fraction (R95) were successively obtained
      from 70% ethanol extracts of P. multiflorum, after being eluted by water, 50%
      ethanol and 95% ethanol and then absorbed by AB-8 macroporous resin. Normal human
      liver L02 cells and liver cancer HepG2 cells were incubated with cell
      supernatants from different fractions and cells. MTT method and inverted
      microscope were adopted to observe the impact of L02 on growth of HepG2 cells,
      screening fractions with damage effect and detect their doses and time effect.
      Giemsa stain showed changes in cell nucleus after administration and flow
      cytometry analysis was used to detect cycle and apoptosis of L02 cells. RESULT:
      MTT method and inverted microscope showed that R50 had significant growth
      inhibition effects on L02 and HepG2 cells. According to giemsa stain and flow
      cytometry analysis, R50 showed different effect on inducing the two cells: there
      are much more apoptotic HepG2 cells than apoptotic L02 cells in each time phase
      (the proportion of the apoptosis cells in HepG2 group were 83.62%, 60.52% and
      74.49%, and ID2 31.02%, 20.57% and 25.32% after treated with R50 for 24, 48, 72
      h. Both cells showed less than 5% of apoptotic cells in the negative control
      group in each time phase). However, there is no significant impact on cycle of
      both cells. CONCLUSION: R50 from P. multiflorum extracts had different damage
      effects on human liver L02 cells and liver cancer HepG2 cells, which was caused
      by different degree of induction on apoptosis of the two cells in nature.

PMID- 22997835
TI  - [Protective effect of ligustrazine hydrochloride on homocysteine-injured ECV304
      cells].
AB  - OBJECTIVE: To detect the protective effect of ligustrazine hydrochloride on
      homocysteine-injured ECV304 cells. METHOD: In the in vitro study, human umbilical
      vein endothelial cells were selected as objects, with homocysteine as the molding
      agent, to judge the injury degree by monitoring NOS and NO contents. Based on
      that, the best homocysteine concentration in ECV304 cells, the best reaction time
      could be determined, and an endothelial cell injury model was established. After
      adding ligustrazine hydrochloride, NOS and NO contents in injured endothelial
      cells were determined to observe the protective effect of ligustrazine
      hydrochloride. RESULT: It was proved that the optimal concentration of
      homocysteine on injured ECV304 cell was 1 mmol x L(-1), the best reaction time
      was 48 h. An injured endothelial cell model was established. At the same time,
      positive drug nitroglycerin and ligustrazine hydrochloride displayed a protection
      effect on injured ECV304 cells, NOS and NO formation were significantly increased
      compared with the model group. CONCLUSION: Ligustrazine hydrochloride has a
      protective effect on homocysteine-injured ECV304 cells. The model established in
      this study can be used to screen anti-myocardial ischemia drugs targeting at an
      endothelial cell protective agent.

PMID- 22997836
TI  - [Analysis on isofraxidin contained in Acanthopanax senticosus extracts and its
      metabolites by UPLC-Q-TOF-MS and automatic data processing technique].
AB  - OBJECTIVE: To analyze isofraxidin and its metabolites in rat plasma, bile, urine
      and feces after the oral administration of A. senticosus extracts. METHOD: After
      the oral administration of 325 mg x kg(-1) of A. senticosus extracts, rat blood
      samples were collected at 1, 1.5, 2, 4, 6 h and bile samples were collected
      during 0-12 h. The above samples were prepared by SPE. Their urine and feces
      samples were collected during 0-12 h and 12-24 h. These samples were analyzed by
      UPLC-Q-TOF-MS and processed using Metabolynx XS. RESULT: M0 was detected in rat
      plasma, bile, urine and feces, isofraxidin glucuronide (M1) was detected in rat
      plasma and bile, which was first reported as the metabolite of isofraxidin.
      CONCLUSION: Isofraxidin can be metabolized in the form of glucuronidation in vivo
      and evacuated in the form of isofraxidin.

PMID- 22997837
TI  - [Pharmacokinetic of four alkaloids of Yanshu injection in Beagel dogs].
AB  - OBJECTIVE: For studying the pharmacokinetic of Yanshu injections in Beagel dogs,
      a sensitive and reproducible LC-MS method for quantitative determination of
      matrine, oxymatrine, sophocarpine and oxysophocarpine in dog's plasma were
      developed and validated using monocrotaline as an internal standard after iv of
      Yanshu injections (Sophorae Flavescentis Radix and Heterosmilacis Japonicae
      Rhizoma). METHOD: The separation of plasma samples was performed on a CN column
      by isocratic elution with methanol-10 mmol x L(-1) NH4Ac-0.02% HCOOH-H2O 90:10 as
      the mobile phase. The plasma concentration of four kinds of alkaloids were
      calculated in dog plasta by detection of healthy dogs given Yanshu injection
      fluid after in twelve hours of plasma samples, All data of concentration-time of
      four kinds of alkaloids were treated with pharmacokinetics program DAS 2. 0.
      RESULT: MT, OMT, SP and OSP have a good linear relationship in 0.01-16.0, 0.02
      60.0, 0.01-4.0, 0.02-16.0 mg x L(-1), respectively. The average recoveries were
      more than 90% and the RSD of precision and stability of the test were less than
      6.4% iv 1.2 g x kg(-1) Yanshu injection, four kinds of alkaloids in rats meet the
      two-compartment open pharmacokinetic model, Cmax and the concentration of the
      original liquid in the proportion of the basic line, the AUC(0-infinity) of
      matrine and oxymatrine, sophocarpine and oxysophocarpine compared to the original
      both in the proportion of liquid increases, the MRT(0-infinity) and t(1/2z) of
      matrine and sophocarpine were less than oxymatrine and oxysophocarpine; four
      kinds of alkaloids apparent volume of distribution matrine > oxymatrine,
      sophocarpine > oxysophocarpine. CONCLUSION: A method with high recovery rate and
      good stabilitywas established to determine the blood concentration of MT, OMT,
      SP, OSP in Yanshu injection and applied in its pharmacokinetics successfully.

PMID- 22997838
TI  - [Impact of saikosaponin on absorption and transport of paeoniflorin in Caco-2
      cell model].
AB  - OBJECTIVE: To study the impact of saikosaponin on absorption and transport of
      paeoniflorin in Caco-2 cell model. METHOD: The concentration of paeoniflorin in
      cell culture medium was measured by UPLC and the apparent permeability
      coefficients (P(app)) was calculated to study differences in bi-direction
      transport of paeoniflorin solutions of different concentrations and its
      compatibility with saikosaponin a, and saikosaponin d in Caco-2 cell model.
      Meanwhile, the electric resistance of Caco-2 cell was determined before and after
      the experiment. RESULT: The amount of paeoniflorin increased linearly with the
      transport of Caco-2 cell monolayer in 4 h, with a lower absorptive permeability,
      which was (0.98 +/- 0.10) x 10(-6), (0.92 +/- 0.09) x 10(-6), (0.89 +/- 0.04) x
      10(-6) cm x s(-1) at the concentration of 20, 50, 100 micromol x L(-1),
      respectively. After compatibility with saikosaponin a and saikosaponin d, the
      absorptive permeability of paeoniflorin increased by 2.37 times and 2.54 times,
      respectively, while the electric resistance of Caco-2 cell was decreased
      significantly after the experiment. CONCLUSION: Saikosaponin a, d can enhance the
      absorption of paeoniflorin in Caco-2 cell monolayer, which may be related to
      saikosaponin's ability to open up intercellular tight junctions among Caco-2
      cells.

PMID- 22997839
TI  - [Study on intestinal absorption of mollugin and purpurin in rats].
AB  - OBJECTIVE: To study the absorption kinetic characteristics of mollugin and
      purpurin in each intestinal segment of rats. METHOD: The in situ single-way
      perfusion rat model was established to study absorption characteristics of
      mollugin and purpurin in each intestinal segment of rats. The volume of
      recirculation fluid was regulated by phenol red. RESULT: Different quality
      concentrations (12.33, 24.66, 49.32 mg x L(-1)) of mollugin and (8.455, 16.91,
      33.82 mg x L(-1)) purpurin showed a concentration gradient of absorption dose in
      each intestinal segment, with the osmotic coefficient increasing to more than 0.2
      x 10(-4) cm x s(-1). In the same concentration, mollugin and purpurin showed an
      identical trend of P(eff) in each intestinal segment in the order of colon >
      duodenum > ileum > jejunum, with a significant difference (P < 0.05). CONCLUSION:
      Mollugin and purpurin are highly permeable in rat intestinal segments, with
      absorption in each segment, while the specific absorption existed in the colon
      segment.

PMID- 22997840
TI  - [Comparative pharmacokinetics study of astilbin after oral administration of
      Yinxieling prescription or Smilacis Glabrae Rhizoma to rats].
AB  - OBJECTIVE: To establish a SPE-HPLC method for analyzing astilbin in rats serum
      and explore the effects of Yinxieling (YXL) prescription and Smilacis Glabrae
      Rhizoma on the pharmacokinetic characteristics of effective components. METHOD:
      Male Sprague-dawley rats were administrated YXL and Smilacis Glabrae Rhizoma
      respectively. At different time points, serum concentration of astilbin was
      extracted by Solid Phase Extraction (SPE) and determined using HPLC method.
      Chromatographic separation was achieved on a reversed-phase Phenomenex C18 column
      with the mobile phase of methanol-acetonitrile-formic acid water solution (0.05%
      formic acid) and gradient elution, temperature of bar was 24 degrees C, flow rate
      was 0.8 mL x min(-1). RESULT: The method showed excellent linearity over the
      concentration range 0.266-53.1 mg x L(-1) of astilbin (r = 0.996). The extract
      recoveries were from 79.0% to 89.1%. Significant diffenerce in pharmacokinetic
      parameter of astilbin including t1/2, Cmax, AUC(0-t), AUC(0-infinity) and MRT
      were obtained through non-compartment model after oral administration of YXL
      prescription comparing with Smilacis Glabrae Rhizoma. CONCLUSION: The method was
      applied to a pharmacokinetic study of astilbin. It indicated that the
      bioavailability of astilbin in YXL enhanced in rats and one of the reasons may be
      that components of prescription affect the pharmacokinetics of astilbin in vivo.

PMID- 22997841
TI  - Small molecule promoted feeder free and adherent differentiation of functional
      neurons from human embryonic and induced pluripotent stem cells.
AB  - While human embryonic stem (hES) and induced pluripotent stem (hiPS) cells offer
      exciting prospects in the fields of regenerative medicine and developmental
      biology, efficient directed differentiation of these cells is still difficult.
      Neural induction protocols often include suspension culture or co-culture with
      other cell types, introducing heterogeneity and complicating analysis. In
      addition, expensive recombinant factors are often used over processes that take
      weeks to complete, making such experiments financially difficult. We have
      developed a fully adherent and feeder free neural differentiation protocol using
      small molecules such as dorsomorphin and common medium supplements. Using this
      protocol, we obtain >90% of cells developing into neural precursors, as measured
      by nestin staining. Neurons derived from these precursors are
      electrophysiologically active. After three weeks of terminal differentiation, we
      obtain functional neurons which fire high-amplitude action potentials upon
      depolarization. A subset of neurons also fires repetitive trains. This protocol
      offers a simpler and less expensive method for investigations involving the
      differentiation of neural precursors and neurons in culture.

PMID- 22997842
TI  - Pivotal role of CD38 biomarker in combination with CD24, EpCAM, and ALDH for
      identification of H460 derived lung cancer stem cells.
AB  - Lung cancer is the number one killer among all cancers and is estimated to kill
      over 170,000 individual in 2010 in the United States. However, little is
      understood about the role of tumor initiating cells in the lung cancer and
      whether these cells play a major role in initiation, drug resistance, and
      metastases of this disease. We have isolated lungospheres from tumors grown in
      mice and have critically examined proposed biomarkers of lung cancer stem cells
      such as ALDH, EpCAM, CD133/1, CD133/2, CD24, and CD38, using global gene
      expression, flow cytometric analysis, and quantitative real time PCR. We present
      evidences that the pattern of overexpression of ALDH and EpCAM, two widely
      discussed biomarkers of cancer stem cells, in the tumor generated by lung cancer
      stem cells in mice are different that could be an indicative of tumor
      aggressiveness. We propose, for the first time, that CD38 in combination with
      CD24 is a biomarkers for H460 derived lung cancer stem cells and could be used to
      elucidate the characteristics of these sub-population of cells. Our results
      demonstrate that the combination of CD24(Low/-)/CD38+ and overexpression of ALDH1
      and EpCAM is the signature of enriched tumor initiating cells in H460 non-small
      cell lung cancer cell line. Our results propose H460-derived cancer stem cells as
      a well defined cell for future comprehensive analysis of putative lung cancer
      stem cells-like cells.

PMID- 22997843
TI  - Primary adipose-derived stem cells enriched by growth factor treatment improves
      cell adaptability toward cardiovascular differentiation in a rodent model of
      acute myocardial infarction.
AB  - The heterogeneous cell population in primary adipose-derived adult stem cells
      (ADAS) and difficulty in keeping their primitive properties have posed certain
      limitations on using these cells for cell therapy. Therefore, our objective was
      to generate a population of cells enriched from the adipose stromal-vascular
      fraction (SVF) with greater differentiation potential than ADAS and to explore
      the mechanism behind the repair of the injured myocardium in vivo. The distinct
      population of adipose stromal cells was enriched by immediate treatment of the
      growth factor cocktail (EGF and PDGF-BB) to the freshly isolated SVF. These cells
      (ADAS-GFs) had distinct cell morphology from ADAS and in average had a smaller
      size. They presented co-expression of CD140a (pericytic markers) and CD34
      (hematopoietic marker), more obvious mesenchymal (CD13, CD29, CD44, CD90 and
      CD117) markers, but rare KDR, and were negative for CD45 and CD31. ADAS-GFs not
      only spontaneously expressed endothelial cell markers and formed capillary-like
      tubes on Matrigel but also clearly expressed early cardiomyocyte marker genes
      when embedded in methylcellulose-based medium. In Sprague-Dawley (SD) rats with
      left anterior descending artery (LAD)-induced myocardial infarction (MI), the
      ADAS-GFs transplanted group had the left ventricular function significantly
      improved compared with the ADAS transplanted group or the control group at 12
      weeks post transplantation. The immunofluorescence staining revealed that the
      transplanted ADAS-GFs expressed GATA4, betamyosin heavy chain and troponin T
      protein but not vWF. More capillaries were also observed around the infarcted
      zone in the ADAS-GFs transplanted group. These data suggested that ADAS-GFs with
      a higher proangiogenic potential may restore the cardiac function of infarcted
      myocardium via the direct cardiomyocyte differentiation as well as angiogenesis
      recruitment.

PMID- 22997844
TI  - Induced pluripotent stem cells for peripheral nerve regeneration.
AB  - Since their discovery in 2006, induced pluripotent stem (iPS) cells have swept
      the scientific world with excitement and possibilities. There have been many
      efforts to create them and differentiate them along desired pathways, but the
      field that may benefit the most from therapeutic iPS cells is neurology. Since
      stem cells are scarce in the nervous system, most damage due to injury or disease
      is permanent. If iPS cells could be differentiated into the appropriate nervous
      system cells, they could provide a way to treat nervous system damage through
      cell replacement therapy. In this review, we will discuss the possibilities of
      iPS cells and their use in the treatment of peripheral nerve injury.

PMID- 22997845
TI  - Pluripotent cells in embryogenesis and in teratoma formation.
AB  - Pluripotent cells of the early preimplantation embryo originate all types of
      somatic cell and germ cells of the adult organism. Permanent pluripotent cell
      lines (ES and EG cells) that were derived from an inner cell mass of blastocysts
      and primordial germ cells have a high proliferative potential and ability to
      differentiate in vitro into a wide variety of somatic and extraembryonic tissues
      as well as germ cells and to contribute to different organs of chimeric animals.
      In some cases pluripotent cells and primordial germ cells can generate teratomas,
      teratocarsinomas and some kinds of seminomas as the results of damages of
      differentiation programme of these cells. Experimental teratomas which formed
      after transplantation of undifferentiated ES and EG cells into immunocompromiced
      mice may provide a unique opportunity to study pluripotent cell specification and
      to develop novel approaches in carcinogenesis investigations. Research of
      signaling and metabolic pathways regulating the pluripotent cell maintenance and
      their multilineage differentiation are essential to search molecular targets to
      eliminate undifferentiated cells in tumors. Analysis of interactions between
      pluripotent cells and differentiated cells of the recipient animals,
      identification of the factors that may drive differentiation ES and EG cells in
      vivo contribute in understanding the mechanisms involved in the determination of
      cell fate during normal development and tumorigenesis. These data are important
      for development of effective and safe stem cell based technologies for
      prospective clinical treatment.

PMID- 22997846
TI  - Potential therapeutic applications of microRNAs in response to DNA damage in
      cancer stem cells.
AB  - Following genomic insults, inefficient DNA repair mechanisms may transform stem
      cell to cancer stem cells that have extensive self-renewal and aberrant
      differentiation properties rendering them highly resistant to chemotherapeutic
      and ionizing radiations and thus may cause tumor relapse in patients. Mature
      microRNAs (miRNAs), new class of modulators are single-stranded RNA molecules of
      20-23 nucleotide (nt) length can form specific base interactions with the mRNAs
      of the genes and mediate the biological processes ranging from tumor development,
      maintenance of stem cell phenotype and stress responses. Due to differential
      functional interactions of miRNAs in cancer stem cells versus normal and
      differentiated cells, various miRNA therapeutic methods may provide a promising
      tool to address aberrant miRNA expression and specifically targeting cancer stem
      cells to cure cancer. Manipulating miRNAs activities by using either antagomirs
      for knock down the oncogenic properties of miRNAs or miRNA mimics to restore the
      tumor suppressor functions in order to correct their aberrant transcript levels
      that can regulate cellular response to damage by modulating apoptotic, cell cycle
      proliferation, DNA repair, invasion and differentiation functions, are also being
      examined. The current article also focuses some of the potential innovative
      strategies to overcome the major concerns for the clinical RNAi translation, the
      delivery and safety. Future studies should be aimed to establish multiple
      clinical trials with the novel gene delivery methods with high transfection
      efficiency, minimum toxicity and tumor targeted ability for miRNA based therapy.

PMID- 22997847
TI  - Stem cell niche failure concerns bone marrow failure--a diagnostic and
      therapeutic consideration.
AB  - Diseases of the bone marrow often referred to as "Bone marrow failure" have
      complicated pathophysiological picture with respect to hematopoietic systemic
      function. The reason for such bone marrow disorder is not well understood till
      date, although some sporadic etiological sources have been described earlier.
      With the advent of current investigations, hematopoietic stem cell involvement
      together with the failure of signaling interaction within the bone marrow niche
      has been found to reveal interesting correlations with the disease onset. The
      present review furnishes justification for bone marrow failure as a concern of
      stem cell niche failure and hints at providing important clues for disease
      diagnosis and therapeutic maneuver.

PMID- 22997848
TI  - Human placental stem cells: biomedical potential and clinical relevance.
AB  - Emerging evidence shows that different adult tissues of the human body harbour
      small amounts of adult mesenchymal stem cells (MSCs) which have the potential to
      give a rise to all cell types of the specific tissue in which they reside. These
      cells were found in human adult bone marrow, muscle, fat, brain, cartilage,
      dental pulp, etc. Depending on the type of host tissue as well as age and state
      of the donor's health, the plasticity of MSCs can vary considerably. Previously
      accomplished research efforts have shown that adult MSCs have a broad therapeutic
      potential due to their ability to differentiate towards multiple adult cell types
      under appropriate conditions. This unique property characterizes adult MSCs as
      potential candidates for biomedical and clinical applications. In the last decade
      human extra-embryonic tissues (placenta, amniotic membranes, and umbilical cord)
      as well as human placental fluids (amniotic fluid and umbilical cord blood), were
      also defined as sources of MSCs, which represents a great interest for the
      biomedical applications. Human placenta is a feto-maternal organ which works as a
      natural barrier between mother and foetus and playing a crucial role for the
      nutrition and immune-tolerance during the whole period of the fetal development.
      Anatomically, the placenta can be divided in four regions: amniotic epithelial,
      amniotic mesenchymal, chorionic mesenchymal and chorionic trophoblastic.
      Immunomodulatory properties of human placenta as well as the clinical
      applicability of such placental parts as amniotic membranes for wound healing,
      treatment of burns, and reconstruction of the oral cavity, will be described. Due
      to the specific structure and functions of placenta, human extra-embryonic MSCs
      represent stem cell types which combine some properties of pluripotent embryonic
      stem cells with other properties of multipotent mesenchymal stem cells. Due to
      the close ontogenic relationship to embryonic stem cells, MSCs derived from
      different placental regions as well as from amniotic fluid and umbilical cord
      blood have immunoprivileged characteristics, posses a broader plasticity, and
      proliferate faster than adult MSCs. Moreover, the human placenta is normally
      discarded after birth, and cells can be isolated avoiding any ethical concerns.
      In this review we summarize and discuss different aspects of development,
      ontogenetic properties, plasticity, and immunomodulatory characteristics of MSCs
      from different placental regions as well as from amniotic fluid and umbilical
      cord blood. In addition the potential of placental MSCs for biomedical and
      clinical applications are discussed.

PMID- 22997849
TI  - Challenges in deriving and utilizing stem cell-derived endothelial cells for
      regenerative medicine: a key issue in clinical therapeutic applications.
AB  - Human pluripotent stem cells such as embryonic and induced pluripotent stem cells
      have the ability to differentiate into all cell types representing the adult
      human body which includes vascular endothelial cells. Vascular endothelial cells
      are of great interest because of the huge role that they play in tissue
      regeneration and engineering. They can be used in cell therapy for the treatment
      of cardiovascular diseases such as myocardial infarction and peripheral arterial
      diseases and also in tissue engineering in the form of vascular grafts or
      vascularized tissue constructs before transplantation. In order for these
      applications to be realized, well-defined, efficient and reproducible
      differentiation protocols are important in directing stem cells differentiation
      into endothelial cells followed by stringent purification and expansion of pure
      populations of these desired cells in vitro. This review focuses on various well
      characterized differentiation procedures that have been used to derive
      endothelial cells from human pluripotent stem cells and the challenges faced in
      using these cells in clinical applications.

PMID- 22997850
TI  - Molecular epidemiology: principles and practices. Foreword.

PMID- 22997852
TI  - Molecular epidemiology: principles and practices. Preface.

PMID- 22997851
TI  - Molecular epidemiology: principles and practices. Foreword.

PMID- 22997853
TI  - Molecular epidemiology: linking molecular scale insights to population impacts.
AB  - In a broad sense, molecular epidemiology is the axis that unites insights at the
      molecular level and understanding of disease at the population level. It is also
      a partnership between epidemiologists and laboratory scientists in which
      investigations are conducted using the principles of both disciplines. A key
      trait of molecular epidemiology is to evaluate and establish the relationship
      between a biomarker and important exogenous and endogenous exposures,
      susceptibility, or disease, providing understanding that can be used in future
      research and public health and clinical practice. When potential solutions or
      interventions are identified, molecular epidemiology is also useful in developing
      and conducting clinical and intervention trials. It can then contribute to the
      translation of biomedical research into practical public health and clinical
      applications by addressing the medical and population implications of molecular
      phenomena in terms of reducing risk of disease. This chapter summarizes the
      contributions and research endeavours of molecular epidemiology and how they link
      with public health initiatives and clinical practice.

PMID- 22997854
TI  - Ethical issues in molecular epidemiologic research.

PMID- 22997855
TI  - Biological sample collection, processing, storage and information management.
AB  - The collection, processing and storage of biological samples occur in the larger
      context of organizations known as biological resource centres or biospecimen
      resources. Biological resource centres are service providers and repositories of
      living cells, as well as genomes of organisms, archived cells and tissues, and
      information relating to these materials. The US National Cancer Institute defines
      a biospecimen resource as a "... collection of human specimens and associated
      data for research purposes, the physical entity where the collection is stored,
      and all relevant processes and policies." The complexities involved in proper
      sample management policies and procedures are often underestimated. Prior to
      initiating a study that will involve the collection of biological samples, many
      decisions need to be made that will affect the quality of the samples and the
      outcome of the study. The appropriate sample type(s) needs to be chosen. The
      processing protocol that will result in samples of suitable quality for the
      intended laboratory analyses must be selected from among various possible
      protocols. Consideration must be given to the proper storage conditions to
      maintain sample quality until analyses are completed. All of these activities
      must be monitored and controlled by appropriate sample tracking and laboratory
      informatics systems. A comprehensive quality management system, with standard
      operating procedures and other appropriate controls, is necessary to assure that
      biological samples are of consistent quality and right for the intended analyses
      and study goals.

PMID- 22997856
TI  - Physical/chemical/immunologic analytical methods.
AB  - Biomarkers can be used to measure the presence of a wide variety of parent
      compounds and metabolites in body fluids and excreta, and serve as biomarkers of
      internal dose. Chemical-macromolecular adducts formed in blood and tissue or
      excreted in urine serve as biomarkers of exposure as well, and in many instances
      reflect both exposure and additional relevant biological processes. An assortment
      of analytical techniques have been developed to identify and measure parent
      compounds, metabolites, chemical-DNA and protein adducts. This chapter will
      discuss many analytical techniques that measure biomarkers in molecular
      epidemiologic studies, including biological, physical, chemical and immunological
      methods.

PMID- 22997857
TI  - Assessment of genetic damage in healthy and diseased tissue.
AB  - DNA, along with other cellular components, is under constant attack by chemical,
      physical, and infectious agents present in the human environment, as well as by
      reactive metabolites generated by physiological processes. Mutations occur as the
      consequence of this damage, but may also be caused by improper DNA repair of
      alterations occurring during normal DNA replication and transcription. Genetic
      damage can occur at the level of the gene (e.g. point mutations, insertions, and
      deletions) or at the level of the chromosome (e.g. aneuploidy, translocations).
      Further, mutations can also take place in mitochondrial DNA. Another form of DNA
      modification is epigenetic methylation of CpG islands, which affects the dynamics
      of chromatin as well as the expression of a large panel of genes. Recent
      technical advances have improved the capacity to detect and quantify genetic and
      epigenetic changes. This chapter summarizes current knowledge on mechanisms of
      DNA damage and mutagenesis, laying out the concepts for interpreting mutations as
      biomarkers in investigating the causes and consequences of cancer. It also
      outlines both established and novel methods for detecting genetic and epigenetic
      changes in normal and diseased tissues, and then discusses their application in
      the realm of molecular epidemiology.

PMID- 22997858
TI  - Basic principles and laboratory analysis of genetic variation.
AB  - With the draft of the human genome and advances in technology, the approach
      toward mapping complex diseases and traits has changed. Human genetics has
      evolved into the study of the genome as a complex structure harbouring clues for
      multifaceted disease risk with the majority still unknown. The discovery of new
      candidate regions by genome-wide association studies (GWAS) has changed
      strategies for the study of genetic predisposition. More genome-wide, "agnostic"
      approaches, with increasing numbers of participants from high-quality
      epidemiological studies are for the first time replicating results in different
      settings. However, new-found regions (which become the new candidate "genes")
      require extensive follow-up and investigation of their functional significance.
      Understanding the true effect of genetic variability on the risk of complex
      diseases is paramount. The importance of designing high-quality studies to assess
      environmental contributions, as well as the interactions between genes and
      exposures, cannot be stressed enough. This chapter will address the basic issues
      of genetic variation, including population genetics, as well as analytical
      platforms and tools needed to investigate the contribution of genetics to human
      diseases and traits.

PMID- 22997859
TI  - Platforms for biomarker analysis using high-throughput approaches in genomics,
      transcriptomics, proteomics, metabolomics, and bioinformatics.
AB  - Global biological responses that reflect disease or exposure biology are kinetic
      and highly dynamic phenomena. While high-throughput DNA sequencing continues to
      drive genomics, the possibility of more broadly measuring changes in gene
      expression has been a recent development manifested by a diversity of technical
      platforms. Such technologies measure transcripts, proteins and small biological
      molecules, or metabolites, and respectively define the fields of transcriptomics,
      proteomics and metabolomics that can be performed at a cell-, tissue-, or
      organism-wide basis. Bioinformatics is the discipline that derives knowledge from
      the large quantity and diversity of biological, genetic, genomic and gene
      expression data by integrating computer science, mathematics, statistics and
      graphic arts. Gene, protein and metabolite expression profiles can be thought of
      as snapshots of the current, poorly-mapped molecular landscape. The ultimate aim
      of genomic platforms is to fully map this landscape to more completely describe
      all of the biological interactions within a living system, during disease and
      toxicity, and define the behaviour and relationships of all the components of a
      biological system. The development of databases and knowledge bases will support
      the integration of data from multiple domains, as well as computational
      modelling. This chapter will describe the technical platform methods involving
      DNA sequencing, mass spectrometry, nuclear magnetic resonance combined with
      separation systems, and bioinformatics to derive genomic and gene expression data
      and include the relevant bioinformatic tools for analysis. These genomic, or
      omics platforms should have wide application to epidemiological studies.

PMID- 22997860
TI  - Measurement error in biomarkers: sources, assessment, and impact on studies.
AB  - Measurement error in a biomarker refers to the error of a biomarker measure
      applied in a specific way to a specific population, versus the true (etiologic)
      exposure. In epidemiologic studies, this error includes not only laboratory
      error, but also errors (variations) introduced during specimen collection and
      storage, and due to day-to-day, month-to-month, and year-to-year within-subject
      variability of the biomarker. Validity and reliability studies that aim to assess
      the degree of biomarker error for use of a specific biomarker in epidemiologic
      studies must be properly designed to measure all of these sources of error.
      Validity studies compare the biomarker to be used in an epidemiologic study to a
      perfect measure in a group of subjects. The parameters used to quantify the error
      in a binary marker are sensitivity and specificity. For continuous biomarkers,
      the parameters used are bias (the mean difference between the biomarker and the
      true exposure) and the validity coefficient (correlation of the biomarker with
      the true exposure). Often a perfect measure of the exposure is not available, so
      reliability (repeatability) studies are conducted. These are analysed using kappa
      for binary biomarkers and the intraclass correlation coefficient for continuous
      biomarkers. Equations are given which use these parameters from validity or
      reliability studies to estimate the impact of nondifferential biomarker
      measurement error on the risk ratio in an epidemiologic study that will use the
      biomarker. Under nondifferential error, the attenuation of the risk ratio is
      towards the null and is often quite substantial, even for reasonably accurate
      biomarker measures. Differential biomarker error between cases and controls can
      bias the risk ratio in any direction and completely invalidate an epidemiologic
      study.

PMID- 22997861
TI  - Environmental and occupational toxicants.
AB  - Biological monitoring is the analysis of human biological materials for a
      substance of interest and/or its metabolites (biomarkers) or a biochemical change
      that occurs as a result of an exposure to provide a quantitative measure of
      exposure or dose. These measures can be used in epidemiological studies either
      directly as estimates of exposure or indirectly in the calibration of other
      exposure assessment methods, such as questionnaires. This chapter will discuss
      important methodological considerations for the implementation of biomarkers of
      exogenous exposure in epidemiology by focusing on biomarker characteristics (e.g.
      variability, half-life) and their application in different study designs.

PMID- 22997862
TI  - Infectious agents.
AB  - The detection and characterization of microbial agents in biological specimens
      are essential for the investigation of disease outbreaks, for epidemiologic
      studies of the clinical course of infections, and for the assessment of the role
      of infectious agents in chronic diseases. Methodological approaches depend on the
      infectious agent, the specimens analysed and the target populations. Although the
      diagnosis of infectious diseases has traditionally relied on direct microscopic
      examination of samples and on the cultivation of microbial agents in vitro, novel
      techniques with increased sensitivity and specificity are now being used on
      samples that can be more easily collected and transported to microbiology
      laboratories (e.g. dried blood spots on filter paper for nucleic acid analysis).
      Direct detection techniques include the microscopic examination of specimens with
      special stains, antigen detection and nucleic acid detection by molecular assays.
      These assays are highly sensitive and provide rapid results for most agents.
      Genomic amplification assays greatly increase the sensitivity of nucleic acid
      based tests by extensive amplification of specific nucleic acid sequences before
      detection. Real-time polymerase chain reaction (PCR) permits genomic
      amplification concurrently with detection of amplified products. Typing
      infectious agents requires additional investigation employing either serologic
      techniques to identify unique antigenic epitopes, or molecular techniques. These
      studies are important for epidemiologic purposes, as well as for the
      investigation of pathogenesis, disease progression, and to establish causality
      between a disease and a microbial agent. Much of bacteriology has relied on
      growth of organisms on artificial media, and on identification of bacterial
      growth with biochemical, serological, or more recently, nucleic acid-based tests.
      The detection of specific antibodies from the host directed against pathogens is
      another strategy to identify current or past infections.

PMID- 22997863
TI  - Dietary intake and nutritional status.
AB  - Though dietary factors are implicated in chronic disease risk, assessment of
      dietary intake has limitations, including problems with recall of complex food
      intake patterns over a long period of time. Diet and nutrient biomarkers may
      provide objective measures of dietary intake and nutritional status, as well as
      an integrated measure of intake, absorption and metabolism. Thus, the search for
      an unbiased biomarker of dietary intake and nutritional status is an important
      aspect of nutritional epidemiology. This chapter reviews types of biomarkers
      related to dietary intake and nutritional status, such as exposure biomarkers of
      diet and nutritional status, intermediate endpoints, and susceptibility. Novel
      biomarkers, such as biomarkers of physical fitness, oxidative DNA damage and
      tissue concentrations are also discussed.

PMID- 22997864
TI  - Assessment of the hormonal milieu.
AB  - The hormonal milieu has been hypothesized to play a role in a range of human
      diseases, and therefore has been a topic of much epidemiologic investigation.
      Hormones of particular interest include: sex steroids; growth hormones; insulin
      like growth factors; stress hormones, such as cortisol; and hormones produced by
      the adipose tissue, termed adipokines. Depending on the hormone, levels may be
      measured in plasma or serum, urine, saliva, tissue, or by assessing genetic
      variation in the hormone or hormone metabolizing genes. Sample collection,
      processing, and storage requirements vary according to the type of sample
      collected (e.g. blood or urine) and the hormone of interest. Laboratory analysis
      of hormones is frequently complex, and the technology used to conduct the assays
      is constantly evolving. For example, direct or indirect radioimmunoassay,
      bioassay or mass spectrometry can be used to measure sex steroids, each having
      advantages and disadvantages. Careful attention to laboratory issues, including
      close collaboration with laboratory colleagues and ongoing quality control
      assessments, is critical. Whether a single hormone measurement, as is frequently
      collected in epidemiologic studies, is sufficient to characterize the hormonal
      environment of interest (e.g. long-term adult hormone exposure) is also an
      important issue. While the assessment of hormones in epidemiologic studies is
      complex, these efforts have, and will continue to, add importantly to our
      knowledge of the role of hormones in human health.

PMID- 22997865
TI  - Evaluation of immune responses.
AB  - This chapter will present some general background material on the cellular,
      biochemical, and genetic mechanisms of the immune system, then focus on specific
      examples that illustrate the promise and pitfalls of using immune biomarkers as
      tools for molecular epidemiologic research and public health practice. Some of
      the most exciting frontiers in medical science will be discussed: early detection
      of cancer through autoimmunity; malignancies that arise from the immune system
      itself; newborn screening for lethal immune deficiencies and latent autoimmune
      disorders; and neurodevelopmental disabilities that could result from maternal
      immune responses, which protect the mother but harm the fetus. The chapter
      concludes with some thoughts about current challenges and future directions.

PMID- 22997866
TI  - Population-based study designs in molecular epidemiology.
AB  - This chapter will discuss design considerations for epidemiological studies that
      use biomarkers in the framework of etiologic investigations. The main focus will
      be on describing the incorporation of biomarkers into the main epidemiologic
      study designs, including cross-sectional or short-term longitudinal designs to
      characterize biomarkers, and prospective cohort and case-control studies to
      evaluate biomarker-disease associations. The advantages and limitations of each
      design will be presented, and the impact of study design on the feasibility of
      different approaches to exposure assessment and biospecimen collection and
      processing will be discussed.

PMID- 22997867
TI  - Family-based designs.
AB  - Family-based designs are used for a variety of reasons in genetic epidemiology,
      including the initial estimation of the strength of genetic effects for a
      disease, genetic linkage analysis by which genetic causes can be sublocalized to
      chromosomal regions, as well as to perform association studies that are not
      confounded by ethnic background. This chapter describes some of the approaches
      that are followed in the initial characterizing of genetic components of disease
      and family-based designs for association analysis and linkage with genetic
      markers.

PMID- 22997868
TI  - Analysis of epidemiologic studies of genetic effects and gene-environment
      interactions.
AB  - This chapter describes basic principles in study design, data analysis, and
      interpretation of epidemiological studies of genetic polymorphisms and disease
      risk, including the assessment of gene-environment interactions. The case-control
      design (hospital-based, population-based or nested within a prospective cohort)
      is frequently used to study common genetic variants and disease risk. Because of
      their widespread use, the analysis of case-control data will be the focus of this
      chapter. Two key considerations in the study design will be addressed: the
      selection of genetic markers to be evaluated, and sample size considerations to
      ensure adequate power to detect associations with disease risk. Single nucleotide
      polymorphisms (SNPs) are the most frequent form of common genetic variation, thus
      the discussion on data analysis will be based on the evaluation of associations
      between SNPs and disease risk. This chapter will begin with the evaluation of
      quality control of genotyping data, which is a critical first step in the
      analysis of genetic data. A description of statistical methods will follow, aimed
      at the discovery of genetic susceptibility loci, including analysis of candidate
      SNPs and genome-wide association studies, haplotype analyses, and the evaluation
      of gene-gene and gene-environment interactions.

PMID- 22997869
TI  - Biomarkers in clinical medicine.
AB  - Biomarkers have been used in clinical medicine for decades. With the rise of
      genomics and other advances in molecular biology, biomarker studies have entered
      a whole new era and hold promise for early diagnosis and effective treatment of
      many diseases. A biomarker is a characteristic that is objectively measured and
      evaluated as an indicator of normal biological processes, pathogenic processes or
      pharmacologic responses to a therapeutic intervention (1). They can be classified
      into five categories based on their application in different disease stages: 1)
      antecedent biomarkers to identify the risk of developing an illness, 2) screening
      biomarkers to screen for subclinical disease, 3) diagnostic biomarkers to
      recognize overt disease, 4) staging biomarkers to categorise disease severity,
      and 5) prognostic biomarkers to predict future disease course, including
      recurrence, response to therapy, and monitoring efficacy of therapy (1).
      Biomarkers can indicate a variety of health or disease characteristics, including
      the level or type of exposure to an environmental factor, genetic susceptibility,
      genetic responses to environmental exposures, markers of subclinical or clinical
      disease, or indicators of response to therapy. This chapter will focus on how
      these biomarkers have been used in preventive medicine, diagnostics, therapeutics
      and prognostics, as well as public health and their current status in clinical
      practice.

PMID- 22997870
TI  - Combining molecular and genetic data from different sources.
AB  - The rapidly growing number of molecular epidemiology studies is providing an
      enormous, often multidimensional, body of evidence on the association of various
      disease outcomes and biomarkers. The testing and validation of statistical
      hypotheses in genetic and molecular epidemiology presents a major challenge
      requiring methodological rigor and analytical power. The non-replication of many
      genetic and other biomarker association studies suggests that there may be an
      abundance of spurious findings in the field. This chapter will discuss ways of
      combining evidence from different sources using meta-analysis methods. Research
      synthesis not only aims at producing a summary effect estimate for a specific
      biomarker, but also offers a unique opportunity for a meticulous attempt to
      critically appraise a research field, identify substantial differences between or
      within studies, and detect sources of bias. Systematic reviews and meta-analyses
      in human genome epidemiology are specifically discussed, as they comprise the
      bulk of the available evidence in molecular epidemiology where these methods have
      been applied to date. Considered here are issues regarding validity and
      interpretation in genetic association studies, as well as strategies for
      developing and integrating evidence through international consortia. Finally,
      there is a brief look at how combining data through meta-analysis may be applied
      in other areas of molecular epidemiology.

PMID- 22997871
TI  - Cancer.
AB  - Molecular epidemiology was introduced in the study of cancer in the early 1980s,
      with the expectation that it would help overcome some important limitations of
      epidemiology and facilitate cancer prevention. The first generation of biomarkers
      has indeed contributed to our understanding of mechanisms, risk and
      susceptibility as they relate largely to genotoxic carcinogens, resulting in
      interventions and policy changes to reduce risk from several important
      environmental carcinogens. New and promising biomarkers are now becoming
      available for epidemiological studies, including alterations in gene methylation
      and gene expression, proteomics and metabolomics. However, most of these newer
      biomarkers have not been adequately validated, and their role in the causal
      paradigm is not clear. Systematic validation of these newer biomarkers is
      urgently needed and can take advantage of the principles and criteria established
      over the past several decades from experience with the first generation of
      biomarkers. Prevention of only 20% of cancers in the United States alone would
      result in 300 000 fewer new cases annually, avoidance of incalculable suffering,
      and a savings in direct financial costs of over US$20 billion each year (1).
      Molecular epidemiology can play a valuable role in achieving this goal.

PMID- 22997872
TI  - Coronary heart disease.
AB  - Until recently, the potential relevance of genetic, biochemical and lifestyle
      factors to coronary heart disease have been studied in relative isolation from
      one another. Although this approach has yielded some major insights, it has
      resulted in a fragmented and incomplete understanding of the relative importance
      and interplay of nature and nurture in the development of coronary risk. New
      opportunities for more integrated, powerful and comprehensive approaches have
      been opened by major developments, including: establishment, collation and
      maturation of relevant population bioresources; emergence of technologies that
      enable rapid and accurate assessment of many genetic and biochemical factors,
      without necessitating assumptions about biological mechanisms; and advances in
      statistical analytical methods. This chapter provides a critical review of the
      strengths and limitations of established and emerging epidemiological approaches
      to the study of the separate and combined effects of genetic, biochemical and
      lifestyle factors in coronary heart disease.

PMID- 22997873
TI  - Work-related lung diseases.
AB  - Work-related respiratory diseases affect people in every industrial sector,
      constituting approximately 60% of all disease and injury mortality and 70% of all
      occupational disease mortality. There are two basic types: interstitial lung
      diseases, that is the pneumoconioses (asbestosis, byssinosis, chronic beryllium
      disease, coal workers' pneumoconiosis (CWP), silicosis, flock workers' lung, and
      farmers' lung disease), and airways diseases, such as work-related or exacerbated
      asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans (a
      disease that was recognized in the production of certain foods only 10 years
      ago). Common factors in the development of these diseases are exposures to dusts,
      metals, allergens and other toxins, which frequently cause oxidative damage. In
      response, the body reacts by activating primary immune response genes (i.e.
      cytokines that often lead to further oxidative damage), growth factors and tissue
      remodelling proteins. Frequently, complex imbalances in these processes
      contribute to the development of disease. For example, tissue matrix
      metalloproteases can cause the degradation of tissue, as in the development of
      CWP small profusions, but usually overexpression of matrix metalloproteases is
      controlled by serum protein inhibitors. Thus, disruption of such a balance can
      lead to adverse tissue damage. Susceptibility to these types of lung disease has
      been investigated largely through candidate gene studies, which have been
      characteristically small, often providing findings that have been difficult to
      corroborate. An important exception to this has been the finding that the HLA
      DPB11(E69) allele is closely associated with chronic beryllium disease and
      beryllium sensitivity. Although chronic beryllium disease is only caused by
      exposure to beryllium, inheritance of HLA-DPB1(E69) carries an increased risk of
      between two- and 30-fold in beryllium exposed workers. Most, if not all, of these
      occupationally related diseases are preventable; therefore, it is disturbing that
      rates of CWP, for example, are again increasing in the United States in the 21st
      century.

PMID- 22997874
TI  - Neurodegenerative diseases.
AB  - Degenerative diseases of the nervous system impose substantial medical and public
      health burdens on populations throughout the world. Alzheimer's disease (AD),
      Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are three of
      the major neurodegenerative diseases. The prevalence and incidence of these
      diseases rise dramatically with age; thus the number of cases is expected to
      increase for the foreseeable future as life spans in many countries continue to
      increase. Causal contributions from genetic and environmental factors are, with
      some exceptions, poorly understood. Nonetheless, molecular epidemiology
      approaches have proven valuable for improving disease diagnoses, characterizing
      disease prognostic factors, identifying high-risk genes for familial
      neurodegenerative diseases, investigating common genetic variants that may
      predict susceptibility for the non-familial forms of these diseases, and for
      quantifying environmental exposures. Incorporation of molecular techniques,
      including genomics, proteomics, and measurements of environmental toxicant body
      burdens into epidemiologic research, offer considerable promise for enhancing
      progress on characterizing pathogenesis mechanisms and identifying specific risk
      factors, especially for the non-familial forms of these diseases. In this
      chapter, brief overviews are provided of the epidemiologic features of PD, AD,
      and ALS, as well as illustrative examples in which molecular epidemiologic
      approaches have advanced knowledge on underlying disease mechanisms and risk
      factors that might lead to improved medical management and ultimately disease
      prevention. The chapter concludes with some recommendations for future molecular
      epidemiology research.

PMID- 22997875
TI  - Infectious diseases.
AB  - Molecular tools have enhanced our understanding of the epidemiology of infectious
      diseases by describing the transmission system, including identifying novel
      transmission modes and reservoirs, identifying characteristics of the infectious
      agent that lead to transmission and pathogenesis, identifying potential vaccine
      candidates and targets for therapeutics, and recognizing new infectious agents.
      Applications of molecular fingerprinting to public health practice have enhanced
      outbreak investigation by objectively confirming epidemiologic evidence, and
      distinguishing between time-space clusters and sporadic cases. Clinically,
      moleculartools are used to rapidly detect infectious agents and predict disease
      course. Integration of molecular tools into etiologic studies has identified
      infectious causes of chronic diseases, and characteristics of the agent and host
      that modify disease risk. The combination of molecular tools with epidemiologic
      methods provides essential information to guide clinical treatment, and to design
      and implement programmes to prevent and control infectious diseases. However,
      incorporating molecular tools into epidemiologic studies of infectious diseases
      impacts study design, conduct, and analysis.

PMID- 22997876
TI  - Obesity.
AB  - The adverse effects of obesity support the use of biomarkers to help elucidate
      disease mechanism, therapeutic interventions, and preventive strategies. Emerging
      biomarkers for obesity-associated cardiovascular disease (CVD), type 2 diabetes
      and cancer play diverse roles in biological pathways including immune modulation
      and fat metabolism. Animal and in vitro data support the association of these
      biomarkers with obesity-associated diseases, but evidence in humans is still
      lacking. In humans, plasma levels of biomarkers are widely used to determine
      risk, but many studies are limited by ethnicity/race, gender or sample size. In
      this chapter, the use of biomarkers in obesity research and in the context of
      CVD, type 2 diabetes and cancer will be discussed. Markers of exposure
      (adipokines), effect (resulting metabolic abnormalities), and susceptibility
      (genetic determinants for obesity and related disorders) are covered for each of
      the three diseases.

PMID- 22997877
TI  - Disorders of reproduction.
AB  - This chapter focuses on biomarkers of reproductive health and disease that have
      been developed in the past 15 years. Due to the gender- and age-dependency of
      most of the advances in measuring reproductive health status and outcomes, these
      biomarkers have been categorized with respect to the unique member of the
      reproductive triad of interest (i.e. mother, father, conceptus). Biomarkers of
      female and male puberty, female reproductive function, fetal and infant
      development, and male reproductive function are discussed. The strengths and
      limitations of developing and implementing biomarkers in reproductive health
      studies over the past decade are explored.

PMID- 22997878
TI  - Studies in children.
AB  - This chapter first discusses the urgent need for prevention of childhood diseases
      that impose a huge and growing burden on families and society. It provides a
      review of recent research in this area to illustrate both the strengths and
      limitations of molecular epidemiology in drawing needed links between
      environmental exposures and illness in children. For illustration, three of the
      major diseases in children are discussed: asthma, cancer and developmental
      disorders. All three impose significant difficulties, have increased in recent
      decades, and are thought to be caused in substantial part by environmental
      factors, such as toxic exposures due to lifestyle choices (i.e. smoking and
      diet), pollutants in the workplace, ambient air, water and the food supply. These
      exogenous exposures can interact with "host" factors, such as genetic
      susceptibility and nutritional deficits, to cause disease. Molecular epidemiology
      has provided valuable new insights into the magnitude and diversity of exposures
      beginning in utero, the unique susceptibility of the young, and the adverse
      preclinical and clinical effects resulting from the interactions between these
      factors. However, molecular epidemiology also faces certain constraints and
      challenges that are specific to studies of the very young, including ethical
      issues, technical issues due to the limited amount of biological specimens that
      can be obtained, and communication of results to parents and communities. These
      challenges are particularly apparent when incorporating the newer epigenetic and
      "omic" techniques and biomarkers into studies of children's diseases.

PMID- 22997879
TI  - Future perspectives on molecular epidemiology.

PMID- 22997880
TI  - [Effects of acrolein on apoptosis of H9c2 cardiacmyocytes with
      hypoxia/reoxygenation injury].
AB  - OBJECTIVE: To determine the cytotoxic effects of acrolein on
      hypoxia/reoxygenation (H/R) injury in H9c2 cardiacmyocytes and investigate the
      intracellular signaling pathways. METHODS: Hypoxia/reoxygenation (H/R) injury
      model was established with H9c2 cells. The H9c2 cells were divided into four
      groups, the control group, acrolein group (ACR), H/R group, acrolein + H/R group
      (ACR + H/R). H9c2 cells pretreated with or without acrolein (10 micromol/L) for
      30 min were exposed to 2 h hypoxia and 16 h reoxygenation. The effect of acrolein
      on the cellular viability and apoptosis of H9c2 cells was measured by MTT assay,
      DAPI stainning and flow cytometry (FCM) respectively. The expression of apotosis
      related proteins (cytochrome c, caspase 9 and caspase 3) in the H9c2 cells was
      detected by Western blot. RESULTS: Compared with mere H/R treatment, the decrease
      in cell viability and increase in the number of apoptotic cells in H9c2 cells
      subjected to H/R were significantly exacerbated in the presence of acrolein (P <
      0.05). The liberation of cytochrome c from mitochondria to cytosol, the cleavages
      of the initiator caspase 9 and the effector caspase 3 have been observed after
      pretreatment with acrolein followed by H/ R in H9c2 cells. CONCLUSION: Acrolein
      could aggravate H/R injury and that this effect may be related, in part, to the
      modification of proteins involved the release of cytochrome c from mitochondria
      to cytosol and activation of caspases cascade reaction.

PMID- 22997881
TI  - [The research on the induction of secretome by adipose tissue for adipose-derived
      stem cells].
AB  - OBJECTIVE: Study the role for adipose tissue-derived stem cells (ADSCs) of
      secretome by adipose tissue and hoped that makes some contributions for the fat
      regeneration. METHODS: Direct adherent culture methods and the flow cytometry
      (FCM) were used to isolate and identify ADSCs. Collected the medium that had
      contained secreted proteins as the conditional medium (CM) and was used to induce
      ADSCs, chemical medium group as the positive control and normal medium group as
      the negative control. The formation of lipid drops was observed through the cell
      morphology, and the reliability was verified through Real-time PCR of the mRNA
      level in vitro. To test the effect of CM on ADSCs in vivo, the absorbable gelatin
      sponge was used as a scaffold for ADSCs. RESULTS: FCM ensured that the cultured
      cells were ADSCs. Significant increased lipid drops and related mRNA levels were
      observed in induced ADSCs cultured for 4 days, which indicated that the CM could
      promote the ADSCs differentiate into adipocytes after cultured for 4 days in
      vitro. The secreted proteins could promote ADSCS differentiate into
      vascularization tissues in vivo. CONCLUSION: The secreted proteome may contain
      some growth factors that can promote ADSCs to differentiate into adipocytes and
      vascularization, which may give new directions for the growth factors that could
      be applied in the repair of soft tissue.

PMID- 22997882
TI  - [Differentiation of human bone marrow mesenchymal stem cells into Leydig or
      steroidogenic cells in vitro].
AB  - OBJECTIVE: To investigate the possibility of differentiating mesenchymal stem
      cells (MSCs) into steroidogenic or testicular Leydig cells in vitro. METHODS: The
      3rd-passage cells of MSCs were divided into 4 groups to be induced and cultured.
      The experimental groups were cultured with conditional medium which consisted of
      luteinizing hormone (LH), human chorionic gonadotrophin (hCG), platelet-derived
      growth factor (PDGF) and interlukin-1alpha (IL-1alpha) as follows. Group A: LH
      0.75 U/mL, hCG 40 U/mL,PDGF 10 ng/mL, IL-1alpha 0.0005 ng/ mL; Group B: LH 0.375
      U/mL, hCG 20 U/mL, PDGF 10 ng/mL, IL-1alpha 0.0005 ng/mL; Group C: LH 0.1875 U/
      mL,hCG 10 U/mL, PDGF 10 ng/mL, IL-1alpha 0.0005 ng/mL. Meanwhile, the control
      group was cultured in basal medium with normal sodium. The results were analysed
      by microscopic observations, 3beta-hydroxysteroid dehydrogenase (3beta-HSD)
      immunocytochemistry and immunofluorescence on the 7th, 14th and 21st day of
      induction respectively. The function of the induced cells was characterized by
      testosterone ELISA. RESULTS: 10-14 days after induction, the induced cells with a
      typical reticular intercellular connection possessed the morphologic
      characteristic of Leydig cells. 3beta-HSD immunocytochemistry and
      immunofluorescence showed that Group A at 21th day had the most positive cells (P
      < 0.05). 21 days of induction revealed a higher testosterone production than
      others (P < 0.05). CONCLUSION: MSCs from human bone marrow are able to
      differentiate into steroidogenic or testicular Leydig cells in vitro. Human bone
      marrow-derived MSC may become important cells for studies of steroidogenic
      differentiation and offer a potential clinical stem cell source for diseases of
      steroidogenic organs.

PMID- 22997883
TI  - [Construct Mxi1 mutation gene expression vector from leukemia cell line KG1].
AB  - OBJECTIVE: To construct the eukaryotic expression vector for Max interacting
      protein 1 (Mxi1). METHODS: The full length cDNA of Mxi1 gene obtained from fetal
      lymphocyte and KG1 cells were inserted into plasmid pDs-red2-N1 respectively to
      generate pDs-red2-N1/Mri1 (wild/mutation type). Then the recombinant vector was
      transfected into Cos-7 cells via liposome. 48 hours post transfection, mRNA of
      Mri1 gene was detected by RT-PCR and Mxi1 protein expression was detected by flow
      cytometry and fluorescence microscope in the Cos-7 cells. RESULTS: The eukaryotic
      expression vector of Mxi1 was constructed and transfected into eukaryotic cells
      successfully. The expression of red fluorescence protein in the transfected Cos-7
      cells was observed under fluorescence microscope which implied the expression of
      Mxi1. The transfect efficiency of both wild and mutation type were in a high
      level in 3 days after transfected, which lasted to 6 d. RT-PCR amplified the
      total RNA extracted from the transfected Cos-7 cells could find increased mRNA
      level of Mxi1 gene. CONCLUSION: We successfully constructed the eukaryote
      expression vector for Mri1 gene; Cos-7 cells transfected with the vector via
      liposome could express Mxi1 protein. These could be useful for the further study
      of the Myc gene modulation.

PMID- 22997884
TI  - [Cloning, expression and purification of human PNAS-4].
AB  - OBJECTIVE: To clone a novel apoptosis-related gene, human PNAS-4, and to get it
      expressed in E. coli. METHODS: Human PNAS-4 gene was amplified by RT-PCR form
      A549 human lung adenocarcinoma cells and inserted into pGEX-6P-1 vector. The
      resulting recombinant plasmid was transformed into E. coli. BL21. Human PNAS-4
      protein was expressed with IPTG induction and the purified protein was identified
      by SDS-PAGE and mass spectrometry. RESULTS: The sequence of the human PNAS-4 gene
      in the recombinant plasmid was identical with that published in GenBank. The
      purified fusion protein of human PNAS-4 with relative molecular mass of 50 000 Da
      was observed in SDS-PAGE analysis, and was identified to be human PNAS-4 by mass
      spectrometry. CONCLUSION: Human PNAS-4 is expressed and purified successfully,
      which would ba a foundation for further research on the function of human PNAS-4
      gene.

PMID- 22997885
TI  - [Zoledronic acid incorporated in chitosan/calcium phosphate ceramic:
      characterization and in vitro response of osteoblast cells].
AB  - OBJECTIVE: To develop a new local delivery system, zoledronic-acid-loaded
      chitosan/calcium phosphate ceramic, and to determine its characterization and in
      vitro response of osteoblast cells. METHODS: Zoledronic-acid-loaded
      chitosan/calcium phosphate ceramic were prepared by solution casting method at a
      concentration of 10(-5), 10(-4), and 10(-3) mol/L, respectively. The
      physicochemical properties of the resulting materials were determined using SEM
      and FTIR. Drug absorbance was measured using CCK-8 colorimetric assay and
      alkaline phosphatase assay to detect the effect of drug-loaded materials on the
      proliferation and differentiation of osteoblasts. RESULTS: After ZOL loading, SEM
      showed that porous calcium phosphate ceramic was coated with chitosan evenly. The
      IR spectra indicated that drug absorption peaks were shifted and a new one was
      formed for the drug-loaded biomaterials. The material at the highest
      concentration could inhibit the proliferation and alkaline phosphatase activities
      of osteoblast cells, but no such effect was found at a drug-loading concentration
      of 10(-4)-10(-5) mol/L. CONCLUSION: We confirmed that the local delivery system
      in this study has ability of loading ZOL. The biomaterial with high drug
      concentrations inhibits the proliferation and differentiation of osteoblasts, but
      not when the drug concentrations are low.

PMID- 22997886
TI  - [Effects of omeprazole on the proliferation and apoptosis of hepatoma cell line
      HepG2].
AB  - OBJECTIVE: To investigate the effects of omeprazole (OME), a proton pump
      inhibitor, on the proliferation and apoptosis of human hepatoma cell line HepG2.
      METHODS: HepG2 cells were cultured to the logarithmic phase, and then treated
      with OME of different concentrations (10, 20, 40, 80, 160 mg/L) for 24 h or 48 h.
      Cell proliferation was evaluated by MTT assay, DNA synthesis was measured with 5
      ethynyl-2'-deoxyuridine (Edu) fluorescent assay and the apoptosis of cells was
      measured by the Hoechst33342 assay. RESULTS: MTT assay showed that OME (40, 80
      and 160 mg/L concentrations) could inhibit the proliferation of HepG2 cells for
      24 h or 48 h treatment (P < 0.05) and 80 mg/L group has strongest effect.
      Compared with that of 24 h treatment, the same concentration of OME could inhibit
      HepG2 more significantly with 48 h treatment. After different concentrations of
      OME treatment for 24 h and then incubation with Edu for 2 h, compared with the
      control group, the proportion of Cells in S phase in 20, 40, 80, 160 mg/L groups
      decreased. Hoechst33342 staining demonstrated that treatment with OME (40, 80,160
      mg/L) for 24 h could significantly promote the cell apoptosis. CONCLUSION:
      Omeprazole could inhibit human hepatoma cell line HepG2 cell proliferation and
      promote apoptosis.

PMID- 22997887
TI  - [The expression of Caspase-3 in granulosa cells of endometriosis treated with
      mifepristone].
AB  - OBJECTIVE: To investigate the effect of mifepristone on the expression of Caspase
      3 in the granulosa cells. METHODS: Forty Sprague-Dawley (SD) female rats with
      (230 +/- 20) g weight were divided into four groups, low-dose group with 1.04
      mg/(kg x d) of mifepristone, middle-dose group with 2.604 mg/(kg x d) of
      mifepristone, high dose group with 10.4 mg/(kg x d) of mifepristone, as well as
      blank group. Mifepristone tablets were given through gastromy in diestrus of rat
      for four weeks. Rats were sacrificed after the treatment, and the the expression
      of Caspase-3 in the granulosa cells of developing follicles was detected by
      immunohistochemical staining. RESULTS: The Caspase-3 protein expression was
      observed in granulosa cells of developing follicles, while the positive
      expression level and integrated optical density (IOD) value were increased along
      with the dosage of mifepristone increasing. The difference among the three dosage
      groups were significant (P < 0.05). CONCLUSION: Regulating Caspase-3 protein
      expression may be one of the ways for mifepristone inducing granulosa cell
      apoptosis.

PMID- 22997888
TI  - [Research on the expression of hemolysin genes of Leptospira in vivo by
      genechip].
AB  - OBJECTIVE: To explore the expression of hemolysin genes of Leptospira in infected
      host. METHODS: Amplified the gene segment of hemolysin genes from the genome of
      Leptospira by PCR for gene probe. Manufacture genechip by the VersArray
      Chipwriter systerm. The total RNAs of Leptospira before and after infection host
      were extracted, reversely transcribed to cDNA, after the random PCR, the products
      were marked with HEX and CY5 respectively, and hybridized to genechip to
      demonstrate the expression of hemolysin genes of Leptospira. RESULTS: The
      hemolysin genes LA1029 (Ratio = 0.65), LA1027 (Ratio = 0.53) were up-regulated
      after infection of host; LA3540 (Ratio = 1.88), LA3937 (Ratio = 5.58), LA1029
      (Ratio = 3.00) were up-regulated and LA4004 (Ratio = 0.67) was down-regulated in
      live than in blood; LA3937 (Ratio = 2.28), LA1029 (Ratio = 2.20) were up
      regulated in kidney than in blood. CONCLUSION: The expression level of hemolysin
      genes exist observable differences with inducement in vivo and in different
      organs. These suggested that these genes are probably involved in the
      pathogenesis and and disease progression.

PMID- 22997889
TI  - [Association of differentially expressed genes in the macrophages of spleen in
      patients with idiopathic thrombocytopenic purpura by cDNA microarray].
AB  - OBJECTIVE: To study the differentially expressed genes of splenic macrophage in
      patients with immune thrombocytopenic purpura. METHODS: Macrophages were isolated
      from the spleen. Total RNA of the macrophages were extracted and reversely
      transcript into cDNA. cDNAs were labeled with Cy5, then hybridized with cDNA
      chips containing 30968 genes. The gene chips were scanned and analyzed for the
      differentially expressed genes. RESULTS: A total of 1545 differentially expressed
      genes were identified by cDNA chip. 718 genes were highly expressed and 827 genes
      were down-regulated. The differently expressed genes include those involved in
      immunologic response, cell adhesion, cell signal transduction, cytoskeleton,
      exercise metabolism, apoptosis, enzyme regulator activity and so on. The pathway
      association analysis were related with Toll-like receptor pathway, Fc gamma
      mediated phagocytosis, MAPK signaling pathway, endocytosis. CONCLUSION: cDNA
      mircroarray is an effective technique in screening for differentially expressed
      genes of the macrophages in patients with ITP. Further analysis of the obtained
      genes will help understanding the pathogenesis of ITP, and the therapeutic
      targets.

PMID- 22997890
TI  - [Key effect genes responding to nerve injury identified by gene ontology and
      computer pattern recognition].
AB  - OBJECTIVE: In order to screen out important genes from large gene data of gene
      microarray after nerve injury, we combine gene ontology (GO) method and computer
      pattern recognition technology to find key genes responding to nerve injury, and
      then verify one of these screened-out genes. METHODS: Data mining and gene
      ontology analysis of gene chip data GSE26350 was carried out through MATLAB
      software. Cd44 was selected from screened-out key gene molecular spectrum by
      comparing genes' different GO terms and positions on score map of principal
      component. Function interferences were employed to influence the normal binding
      of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite
      extension. RESULTS: Gene ontology analysis showed that the first genes on score
      map (marked by red *) mainly distributed in molecular transducer activity,
      receptor activity, protein binding et al molecular function GO terms. Cd44 is one
      of six effector protein genes, and attracted us with its function diversity.
      After adding different reagents into the medium to interfere the normal binding
      of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite
      extension were observed. CONCLUSION: CSC can inhibit neurite extension through
      binding Cd44 on the neuron membrane. This verifies that important genes in given
      physiological processes can be identified by gene ontology analysis of gene chip
      data.

PMID- 22997891
TI  - [Differential expression of miR-21, miR-126, miR-143, miR-373 in normal cervical
      tissue, cervical cancer tissue and Hela cell].
AB  - OBJECTIVE: To investigate the differential expression of miR-21, miR-126, miR-143
      and miR-373 in normal cervical tissue, cervical cancer tissue and Hela cell.
      METHODS: The expressions of miR-21, miR-126, miR-143 and miR-373 were detected by
      real-time PCR in cervical cancer tissue, cervical tissue of benign uterine tumor
      and Hela cell. RESULTS: High expression of miR-21 was observed in cervical cancer
      and Hela cell, while low expression was observed in normal cervical tissue. The
      relative quantification of miR-21 in cerveical cancer was 11.3196 times that of
      miR-21 in normal cervical tissue (P < 0.05). The expression levels of miR-143 and
      miR-373 in cervical cancer and Hela cell were lower than those of normal cervical
      tissue. The relative quantification of miR-143 in cerveical cancer was 0.1553
      times that of normal cervical tissue (P < 0.05), and the relative quantification
      of miR-373 in cerveical cancer was 0.4907 times that of normal cervical tissue (P
      < 0.05). The expression of miR-126 had no significant difference among cervical
      cancer tissue, Hela cell and normal cervical tissue (P > 0.05). CONCLUSION:
      miRNAs are closely related to the occurrence and regulation of cervical cancer.
      The high expression of miR-21 in cervical cancer and Hela cell indicate that it
      may play a possible role of oncogenes, while miR-143 and miR-373 with low
      expression may play the role of tumor suppressor genes.

PMID- 22997892
TI  - [Protective effect of Ligustrazine preconditioning on hepatic energy metabolism
      in ischemia/reperfusion injury of rat].
AB  - OBJECTIVE: Objective to investigate the protective effects of Ligustrazine
      preconditioning against hepatic ischemia/reperfusion injury (IRI) in rats.
      METHODS: Fifty male Wistar rats were randomly allocated into 3 groups: sham
      operation group, in which animals underwent laparotomy, experimental group and
      control group in which were treated with 70% IRI of the liver, especially, the
      animals in experimental group was given intraperitoneal injection of 2 mL
      Ligustrazine per day for 3 days before operation. After the operation, liver
      tissues were harvested at 1 h, 6 h, 24 h and 72 h for the study of
      histomorphological change, the respiratory control ratio (RCR) and phosphorus:
      oxygen ratio (P/O) of hepatocytes mitochondria, and the contents of adenosine
      triphosphate (ATP) of liver tissue. RESULTS: (1) The damage hepatic tissue in
      experimental group was slighter than that in control group at each corresponding
      time-point after operation. (2) The RCR and P/O ratio at each corresponding time
      point were higher in experimental group than those in control group (P < 0.05),
      and all of the two groups recovered after 72 h. (3) The ATP concentration in
      experimental group also was higher than that in control group at each
      corresponding time-point, and recovered faster than control group. CONCLUSION:
      The current results show that Ligustrazine preconditioning may improve energy
      metabolism of rat liver in ischemia reperfusion injury.

PMID- 22997893
TI  - [Effect of Penehyclidine hydrochloride in systemic inflammatory response syndrome
      caused by cardiopulmonary bypass].
AB  - OBJECTIVE: To investigate whether Penehyclidine hydrochloride has effect on the
      inflammatory process and leukocytes in cardiac surgery patients undergoing
      cardiopulmonary bypass. METHODS: 40 rheumatic heart disease patients undergoing
      CPB were randomly divided into Penehyclidine hydrochloride (P) group and control
      (C) group (20 patients in each group). In group P, intravenous drip of 0.01 mg/kg
      of Penehyclidine hydrochloride injection was given before anesthesia, and 0. 015
      mg/kg of Penehyclidine hydrochloride was added into initial volume of CPB. While
      in control group, 0.9% NaCl solution was given instead of injection as a placebo.
      Blood samples were taken before anesthesia (T0), 30 min after CPB (T1), 10 min
      after aortic off-clamping (T2) and 2 hours when CPB was over (T3). Interleukin-6
      (IL-6), tumornecross alpha (TNF-alpha) levels were detected by ELISA. The
      morbility of pneumonia and SIRS caused by CPB was also evaluated. RESULTS: At T2
      and T3, the IL-6 level was higher than T0 and T1 both in group C and group P (P <
      0.05). At T2 and T3, the IL-6 level in group C was higher than that of group P (P
      < 0.05). The TNF-alpha level at T3 was lower than at T1 and T2 in group P (P <
      0.05). There was no significant difference between group P and group C at each
      time point (P > 0.05). The morbility of pneumonia and SIRS was higher in group C
      (P < 0.05). CONCLUSION: Penehyclidine hydrochloride can decrease the levels of
      proinflamnlatory cytokines in plasma and therefore attenuate the morbility of
      pneumonia and SIRS caused by CPB.

PMID- 22997894
TI  - [Comparison of different diagnostic criteria for metabolic syndrome in Sichuan
      population].
AB  - OBJECTIVE: To evaluate the consistency of the diagnostic criteria for metabolic
      syndrome (MS) proposed by World Health Organization 1999 (WHO1999), National
      Cholesterol Education Program Adult Treatment Panel III 2005 (ATP III 2005),
      Chinese Diabetes Society 2004 (CDS2004), and International Diabetes Federation
      2005 (IDF2005), and to identify a more applicable one for people in Sichuan.
      METHODS: A cross-sectional survey on MS was conducted in Sichuan. A total of 3511
      participants were recruited through multistage cluster random sampling. A
      questionnaire was administered to the participants, along with physical
      examinations and laboratory tests involving oral glucose tolerance test and lipid
      profiles. The MS patients were identified by the above-mentioned diagnostic
      criteria. RESULTS: According to the ATP III (2005), the prevalence and age
      adjusted prevalence of MS were 22.4% and 19.8% in Sichuan population
      respectively, significantly higher than those identified by the other 3
      diagnostic criteria. The prevalence of MS increased with age. Men had higher
      prevalence of MS than women (P < 0.05) according to the CDS (2004) and WHO
      (1999). But women had higher prevalence of MS than men according to the IDF
      (2005) and no gender difference in the prevalence of MS existed according to the
      ATP III (2005). No significant difference was found in the prevalence of MS
      between the Han ethnicity and the Yi ethnicity regardless which diagnostic
      criteria were adopted. The 4 MS diagnostic criteria reached a consistency of
      81.17%. The highest consistency (95.70%) occurred between the IDF (2005) and the
      ATP III (2005), with a kappa coefficient of 0.867 (P = 0.000). Significantly
      higher morbidity of myocardial infarction (MI) and/or cerebral stroke was found
      in MS patients regardless which criteria applied. The morbidity of MI and
      cerebral stroke in MS patients identified by the 4 criteria showed no difference
      (P = 0.556). CONCLUSION: ATP III (2005) has stricter criteria for MS than the
      others. The prevalence of MS increases with age. There is no significant
      difference in the prevalence of MS between the Han and Yi ethnicities. In
      Sichuan, the CDS (2004) is more applicable than the others.

PMID- 22997895
TI  - [Risk factors study of ischemic stroke in young adults in Southwest China].
AB  - OBJECTIVE: To analyze the etiology and risk factors of ischemic stroke in young
      adults in Southwest of China. METHODS: This study retrospectively reviewed the
      109 records of all 18-45 year-old patients who were admitted to the West China
      Hospital of Sichuan University from 2008 to 2010. Etiology was classified by
      Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We surveyed the
      risk factors of all the patients. RESULTS: Of 109 patients (male female 1.7 : 1),
      the mean age of onset was (37.9 +/- 6.3) years. An increased occurrence of
      ischemic stroke was found in the older age group, which was significant in 40-45
      years. Regarding stroke subtype, large-artery atherosclerosis was diagnosed in
      57% of cases, cardioembolism in 18%, other determined etiology in 15%, stroke of
      small-vessel occlusion in 5.5%, and undetermined etiology in 4.5%. The older the
      age of the patients was, the high proportion of large-artery atherosclerosis was,
      and significant difference was found between each two age group (P < 0.05). In
      cardioembolism, the most common etiology was rheumatic heart disease with mitral
      stenosis and atrial fibrillation (40%). In stroke of other determined etiology,
      the most common etiology was dissection. The most common dissection was occurring
      in the vertebral system (87.5%). The most common risk factors were hypertension
      (36%), smoking (33%), and hypertriglyceridemia (31%). CONCLUSION: Our study found
      that large-artery atherosclerosis was the most common etiology of ischemic stroke
      in young adults in Southwest of China, and the most common risk factors were
      hypertension, smoking and hypertriglyceridemia.

PMID- 22997896
TI  - [Association study of the 5-HTT polymorphism and posttraumatic stress disorder in
      adolescents].
AB  - OBJECTIVE: To study the association between 5-HTTVNTR polymorphism and
      posttraumatic stress disorder (PTSD) in Chinese Han adolescents after the
      Wenchuan Earthquake, and investigation of the genetic mechanism of PTSD. METHODS:
      Polymerase chain reaction (PCR) was used to detect the distributive frequency of
      5-HTTVNTR polymorphism of 236 PTSD patients (patient group) and 234 normal people
      (control group), Plink version 1.07 was used to analyze the genotyping results.
      RESULTS: The frequency of 5-HTTVNTR allele 12 in PTSD group was significantly
      higher than control group (93.2% vs. 88.9%, chi2 = 5.42, P = 0.020). The 12/12
      genotype in PTSD group and control group was 88.1% and 79.7%; 10/12 genotype was
      10.2% and 19.6%; 10/10 genotype was 1.7% and 1.7%. The distributive frequency of
      all three genotypes (12/12, 10/12, 10/10) showed statistically significant (P =
      0.023). CONCLUSION: The allele 12 of 5-HTTVNTR may increase the risk of PTSD in
      Chinese Han adolescents, 12/12 genotype may be the susceptibility gene, and
      heterozygote 10/12 may act as the protective factor of PTSD.

PMID- 22997897
TI  - [Reliability and validity of the screen for child anxiety related emotional
      disorders in high school students in the 5.12 Wenchuan earthquake stricken
      areas].
AB  - OBJECTIVE: To test the reliability and validity of the Screen for Child Anxiety
      Related Emotional Disorders (SCARED-41) in high school students in the 5.12
      Wenchuan Earthquake stricken areas. METHODS: A multistage cluster random sampling
      method was adopted to select 2729 year 10 and year 11 students from three high
      schools in the earthquake stricken areas for the questionnaire survey using
      SCARED-41. The internal consistency and construct validity of the SCARED-41 were
      evaluated through Cronbach's alpha and exploratory and confirmatory factor
      analyses, respectively. RESULTS: The Guttman split-half correlation for the
      SCARED-41 was 0.940, with the five subscales ranging from 0.734 to 0.860. The
      Cronbach's alpha for the SCARED-41 was 0.937, with the five subscales ranging
      from 0.646 to 0.862. Seven common factors were extracted from the exploratory
      factor analysis, with a percentage of cumulative explained variance of 49.9%.
      Social phobia contributed the most, which accounted for 11.9% of the total
      variance and retained all prior assigned items. Somatic/panic and general anxiety
      came second. The confirmatory factor analysis showed that a modified model
      combining the somatic/panic and general anxiety factors as one generated a better
      fit than the originally assumed construct. RESULTS: SCARED-41 has good
      psychometrics properties. With adequate reliability and validity, SCARED-41 can
      be widely applied for assessing anxiety of students in earthquake stricken areas.

PMID- 22997898
TI  - [Risk factors for acute exacerbation of chronic obstructive pulmonary disease in
      patients who survived the Wenchuan earthquake].
AB  - OBJECTIVE: To investigate the major risk factors for acute exacerbations of
      chronic obstructive pulmonary disease (COPD) and the role of mental status in
      patients who survived the Wenchuan Earthquake. METHODS: A questionnaire survey
      was conducted in 301 COPD patients from the earthquake and non-earthquake areas
      in Sichuan one month, three months and 12 months after the Wenchuan Earthquake.
      RESULTS: A total of 269 patients with COPD completed this study, which included
      133 patients earthquake area and 136 from non-earthquake area. (1) Patients from
      earthquake area had significant higher incidence of acute exacerbations of COPD
      than those from non-earthquake area 3 months (0.57 +/- 0.688 vs. 0.40 +/- 0.601)
      and 12 months (1.82 +/- 1.375 vs. 1.47 +/- 1.366) after the earthquake. (2)
      Patients from earthquake area had significant higher Modified British Medical
      Research Council (mMRC) grades of COPD than those from non-earthquake area 12
      months (P < 0.05) after the earthquake. (3) Patients from earthquake area had
      significant higher prevalence of posttraumatic stress disorder (PTSD) and higher
      scores of Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS)
      than those from non-earthquake area within one month and 3 months after the
      earthquake. The difference in PTSD prevalence remained significant 12 months
      after the earthquake. (4) No significant differences in the prevalence of PTSD
      and the scores of SAS and SDS were found within one month and 3 months after the
      earthquake, though significant improvements were observed 12 months after the
      earthquake for both participants from the earthquake and non-earthquake areas (P
      < 0.01). (5) Patients from earthquake area lived in worse environment than those
      from non-earthquake area during the first 3 months after the earthquake (P <
      0.001). The living environments of both groups improved significantly 12 months
      later (P < 0.001). (6) Binary logistic regression showed that older age, worse
      pulmonary function, psychological disorder, worse living environment were risk
      factors of acute exacerbation of COPD after the Wenchuan Earthquake. CONCLUSION:
      The earthquake caused serious psychological trauma in COPD patients. Older age,
      worse pulmonary function, psychological disorder, worse living environment are
      risk factors associated with acute exacerbation of COPD. COPD patients should
      receive psychotherapy and better living arrangement as early as possible after
      serious disasters.

PMID- 22997899
TI  - [The technology innovation and optimization of clinical application for CT and
      MRI].
AB  - Along with the application of new medical imaging technology, the clinical
      diagnosis and treatment relies more and more on the support of imaging study,
      from health examination to curative effect evaluation. It becomes more prominent
      than ever to protect the safety of patients and to improve the accuracy of
      diagnostic imaging with the increasing number of examinee. X-ray radiation
      hazards and adverse events of contrast agent are major hidden safety risks in the
      imaging process. The new technology of radiation protection, optimization of
      check sequence, as well as the dosage reduction of X-ray scanning can reduce the
      X-ray radiation hazards to examinee. Decreasing the amount of contrast agent can
      reduce the risk of severe adverse events in CT or MRI enhanced scan. Non-contrast
      MRA imaging make angiography possible for the patients with renal insufficiency
      or contrast-allergy. The clinical application of new image techniques, such as
      energy imaging, function imaging and molecular imaging, not only contribute to
      improve the accuracy of diagnostic imaging, but also facilitate diagnostic
      imaging from morphological and anatomic level extending to functional and
      molecular level. It is the only way to meet the growing clinical demands on
      precise imaging with technical innovation and optimization. In order to guarantee
      the benefit for every examinee, we need highly concern about how to avoid any
      possible safety incidents during imaging examination and the waste of medical
      resources caused by repeat examination.

PMID- 22997900
TI  - [MR imaging of polyethylenimine-superparamagnetic iron oxide nanoparticle labeled
      bone marrow mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To explore the optimal concentration of polyethylenimine
      superparamagnetic iron oxide (PEI2k-SPIO) particles for labeling bone marrow
      mesenchymal stem cells (BMSCs) in vitro, then to demonstrate the imaging
      characteristics of the cells by 7.0-T MR scanner. The lowest cell quantity and
      the optimal cell quantity detected on MR was observed. METHODS: Cells at 2nd
      passage were inoculated into the 6-hole plate with cover glass. The different
      concentrations of PEI2k-SPIO (5 microg/mL, 7 microg/mL, 10 microg/mL, 15
      microg/mL, 20 microg/mL) were added into different holes, respectively. After
      labeled with different concentrations of PEI2k-SPIO, the Prussian blue stain was
      used for determining the labeling efficiency. MTT growth curves were used to
      identify the activity of BMSCs and to determine the optimal threshold of SPIO
      nanocomposite particles labeled the stem cells at different PEI2k-SPIO
      concentrations (7, 10, 15, 20 microg Fe/mL medium). To definite the lowest cells
      quantity and the optimal observable cells quantity on MR imaging, 1 x 10(6), 1 x
      10(5), 1 x 10(4) and 1 x 10(3) cells labeled with optimal threshold of PEI2k-SPIO
      and 1 x 10(6) cells unlabeled suspended in 0.2 mL agarose (10 g/L), respectively
      undergone MR scan. RESULTS: MTT growth curves showed the optimal threshold of
      PEI2k-SPIO labeled BMSCs was 7 microg/mL, which indicates has no adverse effects
      on the growth of stem cells. At the opimal concentration (7 microg Fe/mL), the
      lowest observable cell quantity of PEI2k-SPIO-labeled cells for MRI was 1 x
      10(4), and the optimal observable cell quantity was 1 x 10(6). CONCLUSION: At the
      opimal concentration, adverse effect to stem cell activities had not be detected
      when were labeled with PEI2k-SPIO and the clearly image of MRI of labeled BMSCs
      could be obtained.

PMID- 22997901
TI  - [Application value of low-dose computed tomography for the screening of lung
      cancer in high-risk group].
AB  - OBJECTIVE: To analyze the value of low-dose computed tomography (LDCT) in early
      screening of lung cancer in high-risk group. METHODS: LDCT was performed in 1551
      adults over 40-years old (male 1054, female 497) for the screening of lung cancer
      in Examination Center of West China Hospital, Sichuan University, and the
      subjects were divided into high-risk group and non-high-risk group according to
      risk factors of lung caner. The detection rates of lung lesion and lung cancer in
      these two groups were carefully analyzed. RESULTS: In the people over 40-years
      old,the detection rate of pulmonary lesions by LDCT was 54.41% (844/1551), the
      detection rate of nodules was 29.4% (456/1551). Detection rate of lung cancer was
      0.51% (8/1551), while it was 1.21% (7/577) in high-risk group, and 2.01% (6/298)
      in heavy smoker group. The difference of lung cancer detection rate was
      significant (P < 0.05). When stratified with the number of risk factors, the
      detection rate of lung cancer by LDCT was 0.10% (1/974) in the subjects without
      any high-risk factors, 0.98% (5/506) in the subjects with one high-risk factor
      and 2.86% (2/70) in the subjects with more high-risk factors, and the differences
      were stastatically significant (P < 0.05). CONCLUSION: LDCT can detect
      asymptomatic lung cancer sensitively with low radiation dose, which could be
      helpful for the screening of lung cancer.

PMID- 22997902
TI  - [The value of split-bolus 2-phase with virtual non-enhanced scan in CT
      urography].
AB  - OBJECTIVE: To investigate the value of split-bolus 2-phase with virtual non
      enhanced scan in CT urography. METHODS: Eighty (80) patients with urinary
      obstruction were divided into two groups, group A was traditional CT urography
      scan, group B was split-bolus 2-phase with virtual non-enhanced scan. The scan
      sequence of group A included conventional scan first, then enhanced scan in
      arterial phase, parenchyma phase and excretion delayed phase after the injection
      of 100 mL contrast agent. The scan sequence of group B included conventional scan
      and enhanced scan following two bolus injection of contrast; the first injection
      of contrast was 40 mL, the second injection was 60 mL with 15-30 minutes delay,
      then enhanced scan was conducted in arterial and parenchymal phase, the
      parenchymal phase scan was performed with dual energy scanning sequence. The
      image quality of urinary collecting system, the detection of urinary obstructive
      lesion, and radiation dose were compared between the two groups. RESULTS: Between
      the two imaging methods, the imaging quality of urinary system did not show
      significant difference, but radiation dose was statistically significant
      difference. The radiation dose of split-bolus 2-phase with virtual non-enhanced
      scan was only 55% of traditional CTU scan. CONCLUSION: Split-bolus2 phase with
      virtual non-enhanced scan could obtain the same image quality as tranditional
      CTU, while reducing the approximately half the radiation dose.

PMID- 22997903
TI  - [Low-dose chest pain protocol for cardiac and chest imaging using dual-source
      computed tomography].
AB  - OBJECTIVE: To evaluate the clinical value of low-dose chest pain protocol for
      cardiac and chest vascular imaging using dual-source computed tomography.
      METHODS: 102 patients with requests for examinations of cardiac and thoracic
      blood vessels, were scanned in chest pain protocol for angiography. With heart
      electrical impulses dose control techniques, maximum tube current within the R-R
      interval was set up by different heart rate. Patients with a heart rate less than
      or equal to 75 beats/min were divided into two groups: regular-dose group (A) 28
      patients; low-dose group (B) 25 patients. Patient with a heart rate of 76-120
      beats/min were also divided into two groups: regular-dose group (C) 24 patients;
      low-dose group (D) 25 patients. The image quality of pulmonary artery, coronary
      artery and aortic were blind evaluated. The effective dose for each patient was
      calculated and group comparisons were made. RESULTS: Every radiation dose gained
      satisfactory images. No differences in image quality were found between Group A
      and Group B, and between Group C and Group D (P > 0.05). The effective doses of
      Group A (7.09 +/- 0.95) mSv were significantly higher than those of Group B (5.01
      +/- 0.34) mSv. The effective doses of Group C (4.79 +/- 0.91) mSv were
      significantly higher than those of Group D (2.48 +/- 0.43) mSv. CONCLUSION; For
      patients with acute chest pain and relatively stable heart rate, their cardiac
      and thoracic vessels can be shown clearly in images of low-dose chest pain
      protocol, which provides a rapid and clear diagnostic instrument.

PMID- 22997904
TI  - [The value of dual-source dual-energy CT with iodine overlay in the diagnosis of
      acute necrotizing pancreatitis].
AB  - OBJECTIVE: To investigate the clinical value of dual-source computed tomography
      dual-energy Iodine overlay technique in the imaging diagnosis of acute
      necrotizing pancreatitis. METHODS: The imaging data were retrospectively analyzed
      in 67 cases of acute necrotizing pancreatitis underwent contrast-enhanced dual
      source dual-energy CT in portal venous phase. The CT imaging parameters,
      including the difference of CT value between pancreatic parenchyma and necrotic
      lesion, contrast-to-noise ratio of pancreatic parenchyma-to-necrosis, area of
      pancreatic necrosis and score of subjective diagnosis, were measured and assessed
      on CT images of 80 kV, 140 kV, weighted-average 120 kV as well as Iodine overlay.
      RESULTS: The differences of CT value between pancreatic parenchyma and necrosis
      in the images of 80 kV, 140 kV, weighted-average 120 kV and Iodine overlay were
      (67.40 +/- 20.82) HU, (42.87 +/- 14.99) HU, (48.69 +/- 15.82) HU, (33.01 +/-
      10.26) HU, respectively; contrast-to-noise ratios of pancreatic parenchyma-to
      necrosis of each group were 8.36 +/- 3.58, 5.85 +/- 2.65, 7.68 +/- 3.51, 10.60
      4.34; area of pancreatic necrosis of each group was (3.78 +/- 2.68) cm2, (3.28 +/
      2.59) cm2, (3.37 +/- 2.46) cm2, (2.42 +/- 1.98) cm2; the score of subjective
      diagnosis of each group was 3.88 +/- 0.33, 3.31 +/- 0.80, 3.58 +/- 0.66, 2.81 +/-
      0.76, respectively. The four indexes in the images of Iodine overlay were
      significantly different from those of another three groups (P < 0.05). Contrast
      to-noise ratio of pancreatic parenchyma-to-necrosis in the images of Iodine
      overlay was significantly higher than that of another three groups, while the
      difference of CT value, area of pancreatic necrosis and score of subjective
      diagnosis were lower. CONCLUSION; Dual-source CT dual-energy Iodine overlay is
      not helpful to improve subjective judgment in the diagnosis of pancreatic
      necrosis, but contributes to the display of hypoperfusion area around the
      necrosis.

PMID- 22997905
TI  - [Comparison of the efficacy of gadobutrol and multihance in contrast-enhanced MRI
      for diagnosis of brain metastasis in lung cancer].
AB  - OBJECTIVE: To investigate the diagnostic efficacy of gadobutrol for assessing
      brain metastases in lung cancer patients in comparison with multihance. METHODS:
      21 patients with lung cancer suspected of brain metastasis were enrolled in this
      study. All patients underwent twice MRI scans on a 3.0T MRI scanner (Siemens
      MAGENETOM Trio) with 8-channel head coil, first with 0.5 mol/L multihance and
      then with 1.0 mol/L gadobutrol as contrast agent. The dosage of contrast agent
      was set at 0.1 mmol/kg body mass. The interval between the two scans was 24-72
      hours. The detection and delineation of lesions were evaluated visually. The
      signal-to-noise ratios (SNR), contrast-to-noise ratios (CNR) of lesion to normal
      brain white matter and the percentage of lesion enhancement were calculated and
      compared between the two scans by 2 experienced neuroradiologists. RESULTS: One
      patient was excluded because he received radiation therapy between the two scans.
      15 patients were found to have brain metastases with a total of 35 lesions. There
      were no statistical differences between the two scans in SNR, CNR and percentage
      enhancement for both normal brain and lesions (t = 0.545, P = 0.592; t = 1.143, P
      = 2.267; t = 0.592, P = 0.557; t = 0.473, P = 0.639). CONCLUSION: Half-dose
      gadobutrol (1.0 mol/L) can achieve the same enhancement effects compared with
      full-dose multihance (0.5 mol/L).

PMID- 22997906
TI  - [Peripheral MR angiography without contrast agent using fresh blood imaging (FBI)
      with ECG-trigger: initial experience].
AB  - OBJECTIVE: To examine the efficacy of fresh blood imaging (FBI) in detecting
      vascular diseases in lower extremity. METHODS: Thirty-six patients suspected of
      having lower extremity vascular diseases were imaged with a 1.5-T MRI system
      (Toshiba Excelart Vantage). Contrast-enhanced MRA (CEMRA) and FBI technology,
      with maximum intensity projection (MIP) reconstruction were adopted to visualize
      lower extremity vascular. Signal to noise ratios (SNR) were measured on the FBI
      and CEMRA images. Two experienced radiologists assessed the imaging quality of
      peripheral artery MRA on MIP reconstructed images. RESULTS: All patients
      successfully underwent both FBI and CEMRA. All arterial segments were obtained in
      the 36 patients. The SNR values on FBI and CEMRA were 108.39 +/- 9.76 and 87.46
      +/- 14.77 (t = - 6.782, P = 0.001), respectively. There were no significant
      differences in the overall image quality, arterial anatomy and venous overlap
      (chi2 = 0.004, P = 0.947; chi2 = 0.000, P = 1; chi2 = 0.681, P = 0.409). The
      CEMRA motion artifacts were less than FBI (chi2 = 8.744, P = 0.03). CONCLUSION:
      The FBI technique, which shows the vascular disease in lower extremity without
      contrast medium with ECG gating, is considered clinically useful.

PMID- 22997907
TI  - [Determination of ubenimex in human plasma by HPLC-MS/MS].
AB  - OBJECTIVE: To establish a liquid chromatography tandem mass spectrometry method
      for the determination of ubenimex in human plasma. METHODS: The essay was
      conducted with an API 3000 HPLC-MS/MS system consisted of a Ultimate C18 column
      (50 mm x 4.6 mm, 5 microm). The mobile phase consisted of methanol-water-formic
      acid (70 : 30 : 0.05, V/V/V) at a flow rate of 0.2 mL/min. Granisetron was used
      as the internal standard. The sample was extracted by solid phase extraction
      column and was operated under the multiple reaction monitoring mode using the
      electrospray ionization technique in positive mode. RESULTS: The linear range of
      ubenimex was 0.4-4000 ng/mL. The limit of quantity was set at 0.4 ng/mL. The
      within-day and between-day variations were less than 6%. CONCLUSION: This method
      for the quantitative determination of ubenimex was proved to be accurate,
      sensitive, selective and convenient and can be applied in the determination of
      ubenimex in human plasma.

PMID- 22997908
TI  - [Clinical and pathological characteristics and surgical treatment of carotid body
      tumor with endocrine activity].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics and
      surgical treatment of carotid body tumor with endocrine activity (CBT). METHODS:
      Records of seven CBT patients with endocrine activity (Jan, 1991-Aug, 2011) who
      underwent surgical excision of tumor were retrospectively reviewed. The
      operations were performed with the careful peroperative preparation on the
      control of blood pressure, serum potassium and catecholamine. All the tumors were
      studied with the methods of HE staining, immunohistochemistry of chromogranin A
      (CgA) and S-100. RESULTS: All the operations were successfully accomplished and
      the patients recovered quickly. It was confirmed with pathological examination
      that all the tumors were CBT, coming from paraganglioma. Tumor cells and sertoli
      cells were found in HE staining, and all were positive of CgA and S-100. All
      patients were followed up for 12-60 months and no recurrence was found during the
      follow up. CONCLUSION: CBT with endocrine activity presents with identifiable
      clinical and pathological characteristics. The recommended treatment is surgical
      resection, careful perioperative preparation and care is important to avoid the
      severe complication due to the endocrine activity of tumor.

PMID- 22997909
TI  - [Application of the gastric tube in surgical treatment of esophagogastric
      junction adenocarcinoma].
AB  - OBJECTIVE: To evaluate the outcome of gastric tube anastomosis after
      intraperitoneal gastrectomy in the patients with types II and III adenocarcinoma
      of the esophagogastric junction (AEG). From October 2009 to December 2010, 74
      patients with diagnosis of type II or type III AEG were divided groups.
      Traditional anastomosis of gastric remnant with esophagus was performed to 38
      patients in group, while new anastomosis of gastric tube with esophagus was
      performed to 34 patients in gastric tube RESULTS: There were no statistically
      significant differences in baseline data, clinical and pathological
      characteristics between the two groups (P > 0.05). For the postoperative
      complications, 12 (31.6%) patients in traditional and 4 (11.8%) patients in
      gastric tube group occurred gastroesophageal reflux symptoms (P = 0.043). 9
      patients in traditional group and 2 (5.9%) patients in gastric tube group were
      diagnosed as reflux esophagitis postoperative endoscopic examination (P = 0.036).
      CONCLUSION: The anastomosis of gastric tube with the after proximal gastrectomy
      could reduce the incidence of gastroesophageal reflux.

PMID- 22997910
TI  - [Personalized medicine in clinical nephrology].
AB  - Prospects of introduction of personification medicine principles into clinical
      nephrology are discussed with a special emphasis on prognosis of the course of
      chronic kidney diseases and response of the latter to pathogenetic therapy.

PMID- 22997911
TI  - [Endothelial dysfunction and apoptosis at early stage of chronic kidney disease].
AB  - AIM: To study changes in apoptosis and endothelial function in patients with
      chronic kidney disease (CKD) stage I-IIIb (CKDsI-IIIb). MATERIAL AND METHODS: A
      complex of biochemical, enzyme immunoassay and device investigations was used to
      examine 128 patients with CKDsI-IIIb. RESULTS: In CKD stage I reduction of
      endothelium-dependent vasodilation (EDV) was detected in 34% patients, in stage
      II -- in 52 %, in stage IIIa -- y 52 %, in stage IIIb - in 70%. An EDV decrease
      was associated with glomerular filtration rate (GFR), a homocysteine level and
      hemodynamic factors. Elevation of endothelin-1 (ET-1) level was seen in CKDsI in
      41 %, in CKDsII - in 54 %, in CKDsIIIa - in 70 %, in stage IIIb - in 83%
      patients. A negative correlation was observed between the level of ET-1 and GFR
      and positive - with diurnal proteinuria. A significant rise of annexin A5
      concentration versus normal was detected as early as in CKDsI (1,14 +/- 0,68
      ng/ml). In CKDsII annexin A5 was 2,61 +/- 0,75 ng/ml, in CKDsIIIa - 3,75 +/- 0,93
      ng/ml and in CKDsIIIb - 5,16 +/- 1.01 ng/ml. Negative correlations were found
      between annexin A5 level and GFR, a maximal growth of volumetric blood flow rate
      in skin vessels in the acetylcholine test, positive correlations with systolic
      blood pressure, body mass index. CONCLUSION: The levels of ET-1 and annexin A5
      are factors having an independent impact on EDV in patients with CKDsI-II.

PMID- 22997912
TI  - [Clinicopathogenetic characteristics of cardiorenal syndrome in non-alcoholic
      fatty liver disease].
AB  - AIM: To study clinicopathogenetic characteristics of cardiorenal syndrome (CRS)
      in non-alcoholic fatty disease of the liver (nAFDL). MATERIAL AND METHODS:
      Insulin resistance markers, plasma leptin and serum adiponectin concentrations.
      albuminuria, intima-media thickness (IMT) of the common carotid artery (CCA) were
      assessed in 80 patients with metabolic syndrome (60 males and 20 females, mean
      age 44+-11 years) and NAFDL. RESULTS: With increasing signs of affection of
      target organs in NAFDL there was a trend to a significant rise in detection of
      chronic kidney disease (CKD) and carotid artery atherosclerosis, aggravation of
      albuminuria and CCA IMT, lowering of glomerular filtration rate. Leptinemia was
      maximal in CKD patients and directly correlated with albuminuria. Patients with
      CCA atherosclerosis had a significant fall of serum adiponectin which negatively
      correlated with CCA IMT. The latter positively correlated with insulinemia, a C
      peptide plasma level and HOMA index. Serum concentration of adiponectin
      positively correlated with DeRitis index. CONCLUSION: CRS in NAFDL is
      characterized with frequent development of CKD and CCA atherosclerosis defined
      also by unbalance of adiponectin and leptin production.

PMID- 22997913
TI  - [Risk factors for myocardial remodeling at stage II-IV of chronic kidney
      disease].
AB  - AIM: To evaluate frequency and risk factors of development of left ventricular
      hypertrophy (LVH) of the heart in patients with chronic kidney disease (CKD) of
      stage II-IV. MATERIAL AND METHODS: The trial enrolled 83 patients (42 - 51%
      males, 41 - 49% females, mean age 46.7 years) with stage II-IV CKD of non
      diabetic origin. Glomerular filtration rate (GFR) estimated according to Cockroft
      Goult formula was 37,7 ml/min (95% confidence interval from 33,9 do 41,4).
      Chronic renal failure duration averaged 2,7 years (95 % CI from 2.0 to 3.3).
      Arterial hypertension (AH) was diagnosed in 96% patients, hereditary
      predisposition to cardiovascular diseases - in 54%, obesity - in 60%. lipid
      disbolism - in 66%, anemia - in 34 % and hyperphosphatemia - in 45%; 40% patients
      smoked. Echocardiography was performed in all the patients. RESULTS: LVH was
      detected in 31 (37.3%) of 83 patients. With progression of renal failure,
      frequency of registration of LVH increased LVH onset was associated with
      conventional (age, AH, high level of total cholesterol) and renal (lowering of
      GFR, anemia, hyperphosphatemia) factors. Concentric remodeling, concentric LVH,
      eccentric LVH were detected in 31.3, 19.3 and 18.1% patients, respectively.
      Eccentric LVH developed more frequently under the influence of factors associated
      with renal failure (GFR, anemia, hyperphosphatemia, hypocalcemia). Concentric LVH
      was characterized with the highest systolic blood pressure. CONCLUSION: Patients
      with renal dysfunction develop LVH of different geometric model associated with
      both conventional and renal risk factors even at early stages of CKD.

PMID- 22997914
TI  - [Remodeling of the cardiovascular system and development of chronic kidney
      disease in patients with metabolic syndrome and obesity: role of eNOS, subunit
      p22-phox of NADPH-oxidase and MTHFR genes].
AB  - AIM: To examine contribution of polymorphisms of genes of endothelial NO-synthase
      (eNOS), NADPH-oxidase and methylenetetrahydrofolate reductase (mTHFR) to
      development of remodeling of cardiovascular system and chronic disease of the
      kidneys (CDK) in patients with metabolic syndrome (mS) and obesity. MATERIAL AND
      METHODS. Standard clinical and device examinations were made and polymorphisms
      C242T of gene of subunit p22-phox of NADPH-oxidase, G894T of gene of eNOS and
      C677T of gene of MTHFR were studied in 66 MS patients (49 males and 17 females,
      age 19-62 years. RESULTS: The presence of even one prognostically poor allele
      variants of the genes studied was registered in 83 examinees. The genotype
      242TTp22-phox of NADPH-oxidase subunit was associated with the highest insulin
      resistance, allele 894T of gene eNOS- with reduced glomerular filtration rate and
      progression of left ventricular hypertrophy. CONCLUSION: Polymorphism of the
      genes the products of which modulate endothelial function can be considered as
      potential predictors of severity of MS target organs impairment.

PMID- 22997915
TI  - [The role of hyperinsulinemia and insulin resistance in development of chronic
      kidney disease in patients with metabolic syndrome].
AB  - AIM: To examine relations between hyperinsulinemia, insulin resistance (IR).
      components of metabolic syndrome (MS) and predisposition to renal damage,
      MATERIAL AND METHODS: A total of 94 MS patients (64 males and 30 females, age 30
      67 years, mean age 52 +/- 9 years) entered the study. The examination included
      measurement of waist and hip circumference, body mass index (BMI), HOMA index,
      estimation of lipids and immunoreactive insulin concentrations. Renal damage was
      assessed by glomerular filtration rate and urinary excretion of albumin. The
      patients were divided into groups by IR and BMI. RESULTS: A strong correlation
      was found between IR markers and lipid metabolism disorders, hemodynamic
      parameters. Statistics show that IR is an independent unfavourable factor of
      renal damage in MS patients. CONCLUSION: IR is an essential component of MS and
      an independent factor of development of chronic kidney disease in MS patients.

PMID- 22997916
TI  - [Urinary excretion of fibrogenic and antifibrotic growth factors in type 1
      diabetic patients: the interrelationship with diabetic nephropathy].
AB  - AIM: To assess the relation between urinary excretion of profibrotic and
      antifibrotic growth factors, albuminuria and glomerular fibrosis in type 1
      diabetic patients. MATERIALS AND METHODS: 64 patients with diabetes were
      examined, including 25 ones with normal albumin excretion rate (AER), 30
      microalbuminuric and 9 macroalbuminuric patients. Urinary excretion of type IV
      collagen, transforming growth factor-beta 1] (TGF-beta 1), tumor necrosis factor
      alpha (TNF-alpha), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor
      (HGF) and bone morphogenetic protein-7 (BMP-7) was determined by ELISA and
      compared to control (10 healthy subjects). Renal biopsy specimens were assessed
      in 7 patients with normal AER and in 14 microalbuminuric patients. RESULTS: Type
      IV collagen, TGF-beta1 and TNF-alpha excretion was increased significantly in
      patients with micro- and macroalbuminuria as compared to control (all p<0.05).
      Excretion of FGF-2 was increased in macroalbuminuric patients only (p=0.003). No
      marked changes in excretion of antifibrotic growth factors (HGF and BMP-7) were
      observed. TNF-alpha and FGF-2 correlated positively with urinary type IV collagen
      (r=0.37 and r=0.31, respectively). The presence of glomerular fibrosis in renal
      biopsy specimens was associated with higher excretion of TGF-beta1, TNF-alpha and
      FGF-2 (all p<0.05). CONCLUSION: The results suggest that unbalance between
      profibrotic and antifibrotic growth factors in the kidneys plays an important
      role in pathogenesis of diabetic nephropathy. Urinary TGF-beta1, TNF-alpha and
      FGF-2 may offer new possibilities for detection of renal fibrosis in diabetic
      patients.

PMID- 22997917
TI  - [Changes in rheological blood properties in patients with lupus nephritis and IgA
      nephropathy].
AB  - AIM: To compare changes of hemorheological parameters in patients with lupus
      nephritis (LN) and IgA-nephropathy (IgA-N). MATERIAL AND METHODS: Kinetics of
      spontaneous aggregation, disaggregation of red cells in shearing flow, red cell
      deformability were studied in 73 patients with LN including 6 patients with
      active LN with nephrotic syndrome, 38 patients with active LN with urinary
      syndrome, 29 with inactive LN; in 24 patients with a hematuric form of IgA
      nephritis (IgA-N); in 24 healthy volunteers (controls). RESULTS: Patients with LN
      and a hematuric form of IgA-H were found to have disorders of microrheological
      blood characteristics (accelerated formation of erythrocytic aggregates -EA of
      high density) depending on the form and activity of the disease. All LN and IgA-N
      patients exhibited increased time of "coin columbs" formation and accelerated
      aggregation. The largest EA were detected in IgA-H patients. Flow deformation
      ability of the red cells was poor in all the examinees. LN patients showed a
      positive correlation between maximal EA size and hematuria severity even in cases
      of trace proteinuria. A correlation was demonstrated in IgA-N patients between
      IgA level and EA density, between inhibition of GFR and erythrocytic
      deformability index. CONCLUSION: The above findings show deteriorated process of
      aggregation-disaggregation resultant from deterioration of red cell physical
      properties. Severity of hemorheological disorders depends on LN activity.
      Hematuria associated with increased size of EA is an important marker of the
      disease activity Hemorheological disorders in patients with active LN and IgA-N
      are an additional pathogenetic component of hematuria.

PMID- 22997918
TI  - [Serum levels of myeloid-related protein MRP 8/14 (calprotectin) in Armenian
      patients with familial mediterranean fever].
AB  - AIM: The determination of serum myeloid-related protein MRP 8/14 (calprotectin)
      in Armenian patients with FMF before and after treatment with colchicine
      (including colchicine-resistant patients who don't respond to 2 mg of colchicine;
      t patients who don't respond to 1,5 mg of colchicine, and also responders to
      different dose of colchicine) and estimation of the response to antiinflammatory
      therapy. MATERIAL AND METHODS: MRP 8/14 serum levels were measured in 80 FMF
      patients before and after treatment with colchicine and in healthy individuals (n
      = 11) and patients with rheumatoid arthritis RA (n=11) as a control group. Serum
      MRP 8/14 concentration was measured by ELISA (Enzyme Linked-Immuno-Sorbent-Assay)
      method using "Buhlmann" kit (Switzerland) in the laboratory with modern
      equipment. RESULTS: Serum MRP 8/14 concentrations were within a normal ranges in
      healthy individuals and elevated in patients with FMF and RA. MRP 8/14 serum
      levels in FMF patients were higher than in RA patients. Serum MRP 8/14
      concentrations in FMF patients before colchicines therapy were higher than after
      treatment. CONCLUSION: The findings of our study indicate that myeloid-related
      protein MRP 8/14 is a very sensitive marker of the disease activity and response
      to antiinflammatory therapy in FMF.

PMID- 22997919
TI  - [Long-acting erythropoetin efficacy in the treatment of nephrogenic anemia in
      patients with chronic kidney disease during predialysis stage].
AB  - AIM: Comparison of efficacy of 12-month treatment of anemia in patients with
      chronic kidney disease (CKD) of stage III - IV with a long-acting drug
      darbepoetin alpha - aranesp and short-acting drug erythropoietin beta - recormon.
      MATERIAL AND METHODS: A total of 44 patients with CKD of stage III-IVwere divided
      into two groups. Of them, 24 had chronic glomerulonephritis and 20 had
      tubulointerstitial nephritis with verified nephrogenic anemia. Group 1 consisted
      of 22 patients given long-acting erythropoetin (darbepoetin alpha) in an initial
      dose 0,75 mcg/kg each 2 weeks subcutaneously. Group 2 consisted of 22 patients
      matched by age, gender, severity of anemia and renal failure with group 1
      patients given short-acting erythropoietin (erythropoietin beta) in an initial 20
      IU 3 times a week subcutaneous, for 12 months. In the phase of anemia correction
      and supporting therapy the levels of packed red blood cells, Hb, free serum
      ferrum, ferritin, percentage of iron in transfusion, serum albumin in blood
      serum, creatinin, glomerular filtration rate were examined monthly. The patients
      themselves daily measured blood pressure, diuresis, body mass. RESULTS: The
      target level of Hb 110-120 g/l was achieved faster in group 2 than in group 1 (3
      and 4 months, respectively). p < 0.05). In the phase of supporting a target Hb
      level, on the opposite, darbepoetin alpha provided more stable hemopoetin effect
      than erythropoietin beta, darbepoetin alpha median dose being constant in the
      course of the study.

PMID- 22997920
TI  - [Muckle-Wells syndrome caused by a new cryopyrin mutation: effective treatment
      with interleukin-1 antagonist].
AB  - A significant progress in the field of molecular-biological investigations
      resulted in definition of a new group of systemic diseases referred to as
      autoinflammatory. This group comprises familial periodic fevers: periodic disease
      (mediterranean fever), Muckle-Wells syndrome, others cryopirinopathy, TRAPS
      syndrome. As shown by case reports, Muckle-Wells syndrome is not a rare disease,
      its sporadic forms are encountered as well as a less severe variant of
      cryopirinopathy - nonallergic cold urticaria. Awareness of the physicians in
      respect of this pathology is essential especially because early diagnosis enables
      control of this disease with use of biological preparations the spectrum of which
      tends to expansion. Moreover, arrest of inflammation is necessary for prevention
      of development and progression of such prognostically poor complication as AA
      amyloidosis.

PMID- 22997921
TI  - [Efficacy of combined immunocorrection in the treatment of chronic viral
      hepatitis C].
AB  - AIM: To assess efficacy of combined immunocorrection in the treatment of patients
      with chronic viral hepatitis C (CVHC). MATERIAL AND METHODS: Routine
      clinicobiochemical tests, examination of immunological homeostasis (cellular
      immunity, the level of circulating immune complexes - CIC and their molecular
      composition, macrophagal phagocyting system - MPS) were made in two groups of
      CVHC patients: the study group (n=68) and control group (n=66). The control
      patients received standard treatment, the study group received also cyclopheron
      in combination with reamberin. Cyclopheron was given per os in a single daily
      dose 600 mg 2 days, then 3 times a week in a dose 150 mg for 48 weeks. Reamberin
      infusions in a single daily dose 400 ml were made for 5 - 7 days. RESULTS: CVHC
      in exacerbation phase is characterized by the presence of secondary
      immunodeficiency running with T-lymphopenia, low count of peripheral blood
      lymphocytes with CD4+ phenotype and low immunoregulatory index CD4/CD8,
      depression of functional activity of T-cells as evidenced by lymphocyte blast
      transformation test with phytohemagglutinin, inhibition of phagocyting activity
      of monocytes and inhibition of dermal macrophages. This shows subnormal
      functional activity of MPS. CVHC runs with accumulation of CIC in blood serum
      primarily due to increased content of most pathogenic mid- and low-molecular
      .ifactions of immune complexes. Addition ofcyclopheron and reamberin in combined
      treatment of CVHC patients promotes normalization of immunological homeostasis
      which clinically occurs in parallel with achievement of persistent and long-term
      CVHC remission. CONCLUSION: The results of the above investigation support
      pathogenetic validity and prospects of cyclopheron and reamberin inclusion into
      combined treatment of CVHC.

PMID- 22997922
TI  - [Blood microcirculation disorder in patients with bronchopulmonary diseases and
      methods of microcirculation study].
AB  - AIM: To investigate microhemocirculation in patients with bronchopulmonary
      pathology with application of Doppler flowmetry (DFM). MATERIAL AND METHODS:
      Videobronchoscopy (Olimpas or Pentax devices) was performed in 203 patients with
      bronchitis of different inflammation intensity: Functional activity of
      microhemocirculation in bronchial mucosa was studied with endobronchial laser
      Doppler flowmetry (LDF) which was also made in 20 healthy controls. RESULTS: LDF
      grams demonstrated that patients with chronic bronchitis and pneumonia have
      congestive regional microcirculation with low activity of components of
      microcirculatory bed, venous blood congestion, weak blood flow and tissue
      ischemia. High informative value of the method and its availability was shown by
      comparison of LDF-grams on treatment day 7 and 14. CONCLUSION: High informative
      value of LDF procedure is found in diagnosis of vascular and intravascular
      microcirculatory disorders in patients with bronchopulmonary pathology.

PMID- 22997923
TI  - [Nephrotic crisis--an urgent condition in patients with nephrotic syndrome].
AB  - The lecture considers mechanisms of potassium and water retention underlying
      nephrotic syndrome, clinical differences between hypo- and hypervolemic variants
      of nephrotic syndrome, risk factors of nephrotic crisis and its clinical
      symptoms, current approaches to its treatment.

PMID- 22997924
TI  - [Current anti-inflammatory therapy in patients with chronic obstructive pulmonary
      disease].
AB  - The lecture analyses current tools of anti-inflammatory treatment of patients
      with chronic obstructive pulmonary disease (COPD). Anti-inflammatory treatment is
      aimed at a key element of COPD pathogenesis. The results of treatment with main
      anti-inflammatory drugs and methods in COPD management are reviewed as well as
      efficacy of a new anti-inflammatory drug roflumilast in COPD patients.

PMID- 22997925
TI  - [Pharmacological nephroprotection in chronic kidney disease: current
      opportunities and perspectives (review of foreign literature)].
AB  - A brief literature review analyses pharmacoprotective strategy in most widespread
      forms of chronic kidney disease: metabolic syndrome, hypertensive
      angionephrosclerosis. diabetic and non-diabetic nephropathy Nephroprotective
      properties of the blockers of rennin-angiotensin-aldosteron system and other
      antiadrenergic drugs, diuretics, hypolipidemic, antianemic and hypouricemic
      drugs, active metabolites of vitamin D, metphormine and glytasones are reviewed.
      The highest efficacy of combined pharmaconephroprotection is demonstrated.

PMID- 22997926
TI  - [A very unusual infant bone].

PMID- 22997927
TI  - [What the dead cost - concerns with Morbi-RSA (morbidity-based risk adjustment)].

PMID- 22997928
TI  - [Why did he stay intoxicated?].

PMID- 22997929
TI  - [Update 2012: new European guidelines for atrial fibrillation].

PMID- 22997930
TI  - [New European heart failure guideline].

PMID- 22997931
TI  - [E-cigarette without cardiovascular harm].

PMID- 22997932
TI  - [2 promising substances for diastolic heart failure].

PMID- 22997933
TI  - [General antithrombotic therapy practice facing fundamental change].

PMID- 22997934
TI  - [Breakthrough pain treatment is often successful only with a combination].

PMID- 22997935
TI  - [Many patients with erroneous COPD diagnosis for years].

PMID- 22997936
TI  - [Is your hypertensive patient an abdominal, stress or chaos type?].

PMID- 22997938
TI  - [Who has twisted the meaning so badly?].

PMID- 22997937
TI  - [Closing the gaps (interview by Dagmar Jager-Becker)].

PMID- 22997939
TI  - [Need for counseling in artificial insemination has increased by several 100%].

PMID- 22997940
TI  - [Medicine for youth and beauty: smoothing folds and scars].

PMID- 22997941
TI  - [Modern soft tissue augmentation--away from treating the single fold to volume
      replacement in the whole face].

PMID- 22997942
TI  - [Emerging strategies for the prevention and therapy of excessive scars].

PMID- 22997943
TI  - [Pain and sleep disorders].

PMID- 22997944
TI  - [Diabetes and dental health].

PMID- 22997945
TI  - [Community aquired pneumonia: diagnostic work-up and therapy].

PMID- 22997947
TI  - [From the skin to the teeth: little known complications].

PMID- 22997946
TI  - [Herbal preparation eases sore throat and inflammation].

PMID- 22997948
TI  - [Cardiomyocyte structural rearrangement in patients with dilated cardiomyopathy
      and valvular heart disease].
AB  - Light and electron microscopies were used to analyze cardiomyocyte structural
      changes in the dilated left ventricle in patients with dilated cardiomyopathy and
      valvular heart diseases. The patients were found to have cardiomyocyte
      hypertrophy and ultrastructural rearrangement with a tissue-specific reduction.
      There was hypertrophic cardiomyocyte lengthening that continued after these cells
      stopped growing thicker, as well as occurred due to the loss of myofibrils, which
      increased during the cell rearrangement, and directly correlated with the lower
      ejection fraction and higher end-systolic volume of the left ventricle.

PMID- 22997949
TI  - [Hypertrophic cardiomyopathy. Clinical and morphological comparisons].
AB  - The paper comparatively analyzes myocardial morphology in children and adults
      with hypertrophic cardiomyopathy. All the cases analyzed had its obstructive form
      and significant asymmetric left ventricular hypertrophy--hypertrophy of the
      ventricular septum (VS). When stratifying the risk of sudden death from the
      obstructive form of the disease in adults, the most important characteristics are
      shown to be less than 45 years of age, stromal enlargement in the right VS closer
      to the endocardium of the right ventricle; and in some cases this fact must be
      considered when choosing a management tactic.

PMID- 22997950
TI  - [Expression of some biomarkers in primary colon adenocarcinomas and their lymph
      node metastases].
AB  - The samples of colon adenocarcinomas (CAC) and their lymph node metastases from
      22 patients were studied. The expression of thymidylate synthase (TS), vascular
      endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E
      cadherin, beta-catenin, tenascin C (TN), and KAI-1/CD82 in primary CAC and their
      lymph node metastases was compared using an immunohistochemical method. The
      expression of TS, VEGF, EGFR, E-cadherin, TNC, and KAI-1 was statistically
      significant different in primary CAC and involved lymph nodes. Comparison of the
      expression of the markers in the pairs of primary CAC and metastasis revealed
      equal values for TNC and EFGR in 45.5 and 41% of cases, respectively; the number
      of coincidences in the expression of the other markers was insignificant.
      Determination of the expression of molecular biological markers in primary CAC
      and their lymph nodes may serve as a predictor of therapy response and have a
      prognostic value.

PMID- 22997951
TI  - [Determination of the possibilities of targeted therapy for gastric cancer].
AB  - The objective of the investigation whose results are given in the paper was to
      compare a few HER2 testing techniques (immunohistochemistry, fluorescence in situ
      hybridization, and silver in situ hybridization) for adenocarcinomas of the
      stomach and esophagogastric junction. Different antibody clones and in situ
      hybridization kits were comparatively analyzed. Recommendations for the use of
      different testing methods and for the interpretation of their results are given.

PMID- 22997952
TI  - [Markers of stromal invasion during background and precancerous changes of the
      glandular epithelium and in adenocarcinoma of the cervix uteri].
AB  - It is very difficult to identify stromal invasion when the glandular epithelium
      of the cervix uteri is involved. It is necessary to draw a clear distinction
      between its glandular structures and adenocarcinoma in situ, involving the
      preexisting crypts and invasive glands. An attempt was made to assess the
      possibilities of using as markers of invasion the following stromal proteins and
      adhesion molecules: CD44, E-cadherin, beta-catenin, tenascin, and laminin.
      METHODS: Fifty-three cases of benign glandular changes, 66 cases of dysplasias
      and adenocarcinomas in situ, and 47 cases of invasive adenocarcinoma were
      examined. An immunohistochemical study was performed according to the standard
      protocol using the antibodies to CD44, laminin, tenascin, E-cadherin, and beta
      catenin and a semiquantitative assessment of results was made. RESULTS: CD44 was
      found to be redistributed from the cells to the tumor stroma. CD44 was not
      detected in the stroma surrounding the intact glands, so were benign epithelial
      changes. In the tumor environment, there was, on the contrary, a reaction with
      CD44 in 74.5% of invasive adenocarcinomas cases (p < 0.05). The expression of
      tenascin in the invasive adenocarcinomas and around the foci of early stromal
      invasion significantly exceeded that in the stroma around the intact glands and
      dysplastic changes (p < 0.05). All the study groups showed a membrane reaction
      with E-cadherin and beta-catenin, which probably suggested that changes were
      absent in the Wnt signaling pathway. In 70.2% of invasive adenocarcinomas,
      laminin demonstrated a significant cytoplasmic expression in 5-30% of the tumor
      cells predominantly located along the tumor invasion area or in the deepest tumor
      complexes (p > 0.05). CONCLUSION: CD44 and tenascin are of great diagnostic value
      in examining invasive and microinvasive adenocarcinomas of the cervix uteri. E
      cadherin and beta-catenin are of no diagnostic value in the study groups of
      pathological processes. Laminin is a potential marker of stromal invasion;
      however, its expression calls for further investigation.

PMID- 22997953
TI  - [The mother-placenta-fetus system in maternal thyroid diseases].
AB  - In maternal thyroid diseases, the placenta shows an increase in complications
      during pregnancy. There are signs of lesions as alterations, focal sclerosis, and
      fibrinoid necrosis. There is also a circulatory disorder as plethora and
      thrombosis. Progression in these changes correlates with the cases of miscarriage
      and other pathology in the obstetric history. The concurrence of obstetric and
      endocrine diseases increases the risk of pregnancy, labor, and delivery
      complications in different maternal thyroid diseases.

PMID- 22997954
TI  - [Morphological features of papillary thyroid carcinoma with a focal tall-cell
      component].
AB  - The morphological features of papillary thyroid macro- and microcarcinomas of
      classical structure with the focal presence or absence of a tall-cell component
      were comparatively studied. Histological specimens of 55 neoplasms were examined
      in 53 patients. A trend was seen for the higher rate of regional metastasis in a
      group of tall-cell tumors. Additional studies of groups of patients matched for
      sex, age, and extrathyroid tumor extension are required to make a final
      conclusion on the metastatic potential and prognostic features of tumors with a
      tall-cell component. To solve this task, it is expedient to separate neoplasms
      with a focal tall-cell component from the bulk of classical papillary carcinomas.

PMID- 22997955
TI  - [A case of IgG4-related sclerosing disease with lymphadenopathy and thymus
      involvement].
AB  - The paper describes a case of generalized lymphadenopathy clinically recognized
      as malignant lymphoma in a 59-year-old woman. Her death occurred from bilateral
      pneumonia. Autopsy also showed a tumor-like mass in the thymus. On histological
      examination, the lymph nodes, thymus, and spleen exhibited an intensive
      polyclonal IgG4+ plasma cell infiltration. Lymphoid plasma cell infiltration with
      increased count of IgG+ plasma cells, progressive sclerosis, and phlebitis
      obliterans were found in the pancreas and peripancreatic adipose tissue, liver,
      kidney, epicardium, thyroid, pituitary, skin, and other organs. The case was
      regarded as IgG4-related sclerosing disease manifesting itself as lymphadenopathy
      and thymus enlargement.

PMID- 22997956
TI  - [Pancreatic acinar cell adenoma].
AB  - The paper describes two cases of acinar cell adenoma, a rare tumor of the
      pancreas, diagnosed in two 70- and 58-year-old women after surgery. It presents a
      histological description of the tumor and the results of immunohistochemical
      tests performed.

PMID- 22997957
TI  - [Eosinophilic esophagitis in an asthmatic patient].
AB  - The paper contains the results of clinical and morphofunctional examinations of a
      patient with eosinophilic esophagitis complicated by esophageal stenosis and
      detected in the presence of controlled mild persistent asthma and food allergy.
      The endoscopic and morphological diagnostic criteria pathognomonic for this
      disease have been confirmed. The immunohistochemical study of esophageal mucosal
      biopsy specimens revealed the specific features of the composition of an
      infiltrate, which account for the early development of fibrosis and permit
      eosinophilic esophagitis to be referred to as special immunocompetent diseases.

PMID- 22997958
TI  - [Use of scanning microscopic techniques in the study of uteroplacental
      relationships in hypothyroidism].
AB  - Uteroplacental relationships were studied in women with and without
      hypothyroidism, by applying electron, atomic force, and scanning electron
      microscopies, which enables one to gain more insight into morphometric
      characteristics. Moreover, not only fixed, but also native materials were used,
      which brings the studies to a live object and opens up new avenues for rapid
      diagnosis. The use of gross and trace analysis allows the biochemical parameters
      of the structure of uterine and placental tissues to be studied for an additional
      diagnosis and development of treatment options.

PMID- 22997959
TI  - [Molecular genetic study of B- and T-lymphocyte clonality in the diagnosis of non
      Hodgkin's lymphomas].
AB  - The value of molecular genetic methods in the current diagnosis of
      lymphoproliferative diseases is estimated. A standardized BIOMED2 protocol for
      these studies is described. The merits and demerits of this method are
      considered.

PMID- 22997960
TI  - [Gastrointestinal stromal tumors].
AB  - The paper considers the current aspects of the morphology, immunohistochemistry,
      molecular biology of gastrointestinal stromal tumors (GIST). It describes the
      major signs of different histological types of GIST, which depend on the
      morphological, immunohistochemical types of interstitial cells of Cajal. Problems
      in the primary diagnosis and prognosis of GIST are discussed.

PMID- 22997961
TI  - Hemangioblastic characteristics of cancer stem cells in chronic myeloid leukemia.
AB  - BACKGROUND: Overwhelming evidence from Chronic Myeloid Leukemia (CML) research
      indicates that patients harbor quiescent CML stem cells that are responsible for
      blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first
      suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also
      being investigated. METHODS: Here we isolated fetal liver kinase-1-positive
      (Flk1+) cells from CML patients and we tested their biological characteristics.
      In addition, endothelial and hematopoietic differentiation assays were also
      performed to test their cancer stem cell ability. RESULTS: We found these cells
      expressed the BCR/ABL specific CML oncogene. Co-culture assay also indicated they
      could promote HSC blast colonies. Further studies showed they could differentiate
      not only into endothelial lineages but also into erythroid cells at the single
      cell level. CONCLUSIONS: Fetal bone marrow-derived Flk1+CD34- multipotent stem
      cells have the capacity for self-renewal and multilineage differentiation even
      after being expanded for more than 50 cell doublings, they might be the cancer
      stem cells and a target source in the treatment of CML.

PMID- 22997962
TI  - Preanalytical and analytical considerations for measuring nitric oxide
      metabolites in serum or plasma using the Griess method.
AB  - Nitric oxide (NO) plays numerous important roles in many biological systems and,
      therefore, research in this field, which impacts all aspects of biology and
      medicine, especially NO measurement, is steadily increasing. Nitric oxide has a
      short biological half-life, making its direct determination in vivo difficult.
      Therefore, currently assessment of nitrite and nitrate (NOx) in biological fluids
      seems to be the most suitable method to assess NO synthesis in vivo. The most
      frequently used method of NOx analysis is based on the Griess reaction. Although
      measurement of NOx by the Griess assay is simple and cheap, the accurate
      determination of plasma/serum concentrations of nitrate/ nitrite using the Griess
      assay is prone to interferences and can be influenced by several factors. The aim
      of this study was to overview preanalytical and analytical considerations for
      measuring NOx in serum or plasma using the Griess assay.

PMID- 22997963
TI  - Renal outcome in equipotent antihypertensive treatment with telmisartan, ramipril
      and in combination in SHR-SP rats.
AB  - BACKGROUND: The ONTARGET trial revealed an association of ACEI/ARB combination
      treatment (telmisartan and ramipril) with adverse renal outcome versus respective
      monotherapy; preclinical evidence regarding renal outcome in ACEI/ARB combination
      treatment is scarce. METHODS: Spontaneously hypertensive stroke prone rats (SHR
      SP) rats on a salt-rich diet were randomly allocated to 4 groups: SHR (untreated,
      n = 24), SHR + telmisartan (SHR-T, 2.39 +/- 0.69 mg/kg bw; n = 27), SHR +
      ramipril (SHR-R, 6.28 +/- 3.48 mg/kg bw; n = 27) and combination treatment (SHR
      TR, 0.51 +/- 0.14 mg/kg bw; same dose for telmisartan and ramipril; n = 26).
      Study duration was 12 weeks, blood pressure was assessed weekly and doses were
      adjusted to maintain equal blood pressure. Finally, blood and urine samples were
      obtained and kidneys were harvested for histological studies. RESULTS: Blood
      pressure in untreated rats rose to a maximum of 239 mmHg, whereas in all
      treatment groups it remained stable between 140 and 150 mmHg. Mortality was 50%
      in the untreated group, whereas all treatment groups survived completely. Renal
      function--as indicated by plasma urea and cystatin c--was significantly worse in
      SHR-TR animals compared to all other groups. With plasma creatinine a similar
      trend was observed. All treatment options significantly decreased albuminuria.
      Renal glomerulosclerosis was decreased by monotherapy, whereas combination
      therapy failed to have a significant effect. Interstitial fibrosis was decreased
      to a similar extent by all treatment options. CONCLUSIONS: ACEI/ARB combination
      treatment failed to render significant additional benefits on renal outcome in
      hypertensive rats when compared to monotherapy. Instead our data indicate that
      dual RAAS blockade might have an adverse effect on kidney function and histology
      when compared to monotherapy in salt-loaded SHR-SP.

PMID- 22997964
TI  - Analytical performances of the newly developed, fully automated Kryptor Copeptin
      assay: which impact factor for myocardial infarction rules out in the emergency
      department?
AB  - BACKGROUND: We evaluated the essential assay characteristics of the newly
      developed, fully automated Kryptor Copeptin assay including the assay
      performances and the clinical implications in parallel with the dosage of the
      cardiac Troponin I (cTnI) in patients presenting to the Emergency Department with
      chest pain with or without ECG abnormalities. METHODS: Analytical performance of
      the B-R-A-H-M-S Copeptin Kryptor was carried out according to the CLSI protocol
      EP17-A, volume 24, number 34 [3] including linearity imprecision, determination
      of quantification, and detection limits. An evaluation of the clinical
      concordance between cTnI and copeptin results was performed on consecutive
      patients, with chest pain suggestive of acute coronary syndromes (ACS), admitted
      to the Emergency Department of our hospital. RESULTS: At a total imprecision of
      20% (which corresponds to the limit of the quantification) and the level giving a
      CV of 10%, the functional sensitivity was approximately 10.4 and 23 pmol/L,
      respectively. The mean detection limit for the B-R-A-H-M-S Copeptin Kryptor assay
      was 8 pmol/L (range 5.57-10.37 pmol/L) in our study. Clearly, the combination of
      the cTnI and copeptin markers at the decision limit of 0.04 microg/L and 10.4
      pmol/L, respectively, improves the diagnosis of exclusion of ACS. CONCLUSIONS:
      The combination of negative troponin and negative copeptin (< quantification
      limit) could improve rapid sorting of ACS patients in an emergency. The Copeptin
      Kryptor assay is a useful diagnosis tool to rule out ACS and might be further
      enhanced by the recent development of sensitive troponins.

PMID- 22997965
TI  - Performance evaluation of the Access FT3 and FT4 assays, comparison with Immulite
      and AxSym, and the relationship to TSH values.
AB  - BACKGROUND: Different FT3 and FT4 assays report significantly different results.
      We compared the distribution of FT3 and FT4 in a cohort of Swiss patients
      measured with DxI 800, AxSYM, and Immulite 2000. METHODS: TSH, FT3, and FT4
      values were measured in 1,938 serum samples. Patients were classified on the
      basis of their TSH values as low, normal, and high. For each class of TSH values,
      concordances of FT3 and FT4 results were determined among the three assays.
      RESULTS: For low TSH values in all three assays FT3 (FT4) concordance of DxI -
      AxSYM, DxI--Immulite, and AxSYM--Immulite was determined as 83.1%, 76.2% 68.5%
      (60.8%, 74.6%, 83.1%), for normal TSH as 89.2%, 79.0%, 75.3% (83.9%, 85.5%,
      83.1%) and for elevated TSH as 78.0%, 86.0%, 78.0% (84.0%, 90.0%, 90.0%),
      respectively. Low FT4 concordance rates with DxI 800 were mainly caused by its
      FT4 upper reference limit of 14.1 pmol/L. Using a cut-off of 16.1 pmol/L
      concordances with AxSYM and Immulite were improved to 77.7% and 86.9% (low TSH),
      92.5% and 96.2% (normal TSH), and 90.0% and 92.2% (high TSH). Low FT3 concordance
      rates with Immulite were caused by its low FT3 upper reference limit of 6.29
      pmol/L as 11.6% of patient samples with normal TSH value showed unusually
      elevated FT3 results. CONCLUSIONS: We showed an overall good concordance of FT3
      and FT4 results, when stratified according to corresponding TSH values and the
      appropriate reference range is used. However, our data also show that problems of
      interpretation of results based on numerical values have yet not been solved.

PMID- 22997966
TI  - Early urinary and plasma biomarkers for experimental diabetic nephropathy.
AB  - BACKGROUND: As the prevalence of diabetes rises, its complications such as
      diabetic nephropathy affect an increaseing number of patients. Consequently, the
      need for biomarkers in rodent models which reflect the stage and course of
      diabetic nephropathy is high. This article focuses on Heart-type fatty acid
      binding protein (H-FABP), osteopontin (OPN), nephrin, and Neutrophil gelatinase
      associated lipocalin (NGAL) in urine, and kidney injury molecule (KIM)-1,
      clusterin, and tissue inhibitior of metalloproteinases (TIMP) 1 in plasma in uni
      nephrectomized rats with streptocotozin-induced type 1 diabetes mellitus, a
      common animal model to explore renal impairment in the setting of diabetes
      mellitus. METHODS: 23 male Wistar rats were uni-nephrectomized and subsequently
      divided into two study groups. The diabetic group received streptozotocin (STZ)
      via tail-vein injection, the non-diabetic group received citrate buffer without
      STZ. Subsequently, blood glucose, body weight, and blood pressure were checked
      regularly. After 18 weeks, animals were placed in metabolic cages, blood and
      urine obtained and subsequently organs were harvested after sacrifice. RESULTS:
      Blood glucose levels were highly increased in diabetic animals throughout the
      experiment, whereas systolic blood pressure did not differ between the study
      groups. At study end, classical biomarkers such as urinary albumin and protein
      and plasma cystatin c were only slightly but not significantly different between
      groups indicating a very early disease state. In contrast, urinary excretion of H
      FABP, OPN, nephrin, and NGAL were highly increased in diabetic animals with a
      highly significant p-value (p < 0.01 each) compared to non-diabetic animals. In
      plasma, differences were found for calbindin, KIM-1, clusterin, TIMP-1, and OPN.
      These findings were confirmed by means of the area under the receiver operating
      characteristic curve (ROC-AUC) analysis. CONCLUSIONS: In summary, our study
      revealed elevated levels of new plasma and urinary biomarkers (urinary
      osteopontin, urinary nephrin, urinary NGAL, urinary H-FABP, plasma KIM-1, plasma
      TIMP-1) in uni-nephrectomized diabetic rats, an established rat model of diabetic
      nephropathy. These biomarkers appeared even before the classical biomarkers of
      diabetic nephropathy such as albuminuria and urinary protein excretion. The new
      biomarkers might offer an advantage to urinary albumin and plasma cystatin c with
      respect to early detection.

PMID- 22997967
TI  - Usefulness of cytokeratin-19, galectin-3, and Hector Battifora mesothelial-1 in
      the diagnosis of benign and malignant thyroid nodules.
AB  - BACKGROUND: Having been asymptomatic, most thyroid nodules are found
      incidentally. In the absence of a specific diagnostic marker of malignant thyroid
      nodules, it is difficult to microscopically diagnose the benign or malignant
      nature of nodules. METHODS: In the present study, the goal is to investigate the
      expression of cytokeratin-19 (CK-19), galectin-3 (Gal-3), and Hector Battifora
      mesothelial-1 (HBME-1) in thyroid nodules, and to assess their diagnostic value
      as markers in the differential diagnoses of benign and malignant thyroid nodules.
      Conventional Immunohistochemistry (IHC) was used on formalin-fixed, paraffin
      embeded blocks of 150 cases of benign and malignant thyroid lesions. The benign
      group included 28 cases of follicular adenoma (FA) and 44 cases of thyroid
      nodular goiter. The malignant group included 72 cases of papillary thyroid
      carcinoma (PTC) and 6 cases of follicular thyroid carcinomas (FTC). RESULTS: It
      was statistically found that there were strikingly significant differences for
      the three markers in the distinguishing diagnosis of malignant and benign thyroid
      nodules (p < 0.01). However, there were no significant differences for the
      expression of the three markers among two different subtypes in the malignant
      group. What is more, no significant relationship was found between the expression
      of CK-19, Gal-3, or HBME-1 and gender, age, tumor size, focal lymphocytic
      infiltration, or lymph node metastasis in thyroid nodules. CONCLUSIONS: The
      combined use of CK19, Gal-3, and HBME-1 is of practical value in the diagnosis
      and differential diagnosis of benign and malignant thyroid nodules.

PMID- 22997968
TI  - Design of a biological method for rapid detection of presence of PCR inhibitors
      in aged bone DNA.
AB  - BACKGROUND: Molecular human identification is one of the most important tests
      performed in forensic laboratories. Some of these tests are applied for
      identification of human remains from natural disasters, wars, etc., but problems
      may occur as a result of DNA degradation and external DNA contamination. We
      investigated effects of bacterial DNA on identifying the presence or absence of
      PCR inhibitors in aged bone DNA. METHODS: DNA samples were extracted from blood,
      bone remains and Escherichia coli. These DNA were amplified using human and
      bacterial specific primers. RESULTS: Using different blood, aged bone, and
      bacterial DNA dilutions along with PCR based methods; we checked their positive,
      negative effects, or detecting presence of inhibitors in aged bone DNA by PCR
      method. CONCLUSIONS: Our observation indicated that the addition of bacterial DNA
      could be a valid biological method for testing the quality of bone DNA to enable
      us to obtain a usable profile for the identification of human remains. This
      method will help to test the presence of inhibitors, quantity or even quality of
      DNA which are of importance in profiling archeological remains. Our method will
      help to determine if PCR failure is due to presence of inhibitors or lack of
      amplifiable DNA either because of degradation, minute amount or absence of human
      DNA.

PMID- 22997969
TI  - Reference intervals for common biochemical analytes in serum and plasma of a
      random adult population in the Greater Accra Region of Ghana.
AB  - BACKGROUND: The reference interval (RI) is arguably the most widely used decision
      making tool in clinical practice. Using the manufacturer's reference values may
      not be appropriate for other ethnic populations. OBJECTIVE: The objective was to
      determine the reference intervals (RI) of Ghanaians and compare them to that
      provided in kits. METHODS: 6300 adults, 25-65 years were selected by cluster
      sampling from three communities in the Greater Accra Region, Ghana. A total of
      4733 (male/female ratio = 1:1.5) participated. Fasting Blood Glucose (FF), 2-hour
      post-glucose plasma glucose (2HPP), total cholesterol (TCHOL), high density
      lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C),
      triglycerides (TG), uric acid (UA), urea (U), albumin (ALB), alkaline phosphatase
      (ALP) were measured. RESULTS: Male and female mean ages were 44.9 +/-14.7 and
      44.0 +/-14.6 years, respectively. Most assays had mean values between the 25th
      and 75th percentile apart from HDL-C whose mean values fell within the 50th
      percentile. Thus half of the manufacturers RI (MRI) represented <25 percentile
      for FF, 2HPP, LDL-C, ALB and ALP. The MRI for Urea was < 25th - > 97.5th.
      CONCLUSIONS: Mean values of most of the parameters determined represented the
      25th - 75th and not the 95th or 97.5th percentile.

PMID- 22997970
TI  - Anemia in chronic renal disease: evaluation of inflammatory activity on
      erythropoiesis and iron metabolism in patients not submitted to dialysis
      treatment.
AB  - BACKGROUND: Inflammatory activity is one of the factors involved in the
      physiopathology of anemia in patients with chronic kidney disease (CKD). The
      majority of studies on anemia, inflammation, and disturbances of iron metabolism
      have focused on patients in end-stage renal failure and dialysis therapy.
      However, anemia and inflammation are present in patients in previous stages of
      renal failure. The objective of this study was to evaluate the possible influence
      of inflammatory activity on erythropoiesis and iron metabolism in CKD patients
      without dialytic treatment. METHODS: 114 CKD adult patients were studied.
      Patients with anemia (n = 72) were compared with those without anemia (n = 46).
      Anemic patients were classified as renal anemia (n = 46) or iron deficiency
      anemia (n = 26). In addition the total group was analyzed according to the degree
      of renal dysfunction. Iron status, erythropoiesis activity (soluble transferrin
      receptor and erythropoietin determinations), and inflammatory activity (C
      reactive protein, interleukin-6, interleukin-lp, and neopterin determinations)
      were measured using commercial kits. Reticulocyte hemoglobin content (Ret-Y) was
      also determined. RESULTS: Interleukin-6, interleukin-li, and neopterin
      concentrations were higher in the anemic group when compared with those without
      anemia and controls. There was no difference in C-reactive protein values between
      CKD with and without anemia, although both of them had showed elevated levels
      when compared with controls. Ret-Y values were lower in iron deficiency anemia
      when compared with renal anemia and controls. An inverse correlation between
      interleukin-6 and hemoglobin (r = -0.4287, p= 0.0002) was observed only in the
      renal anemia group. It was observed that anemia has a tendency to worsen as renal
      function deteriorates. Reticulocyte count was lower and neopterin concentrations
      were higher in more advanced renal failure stages. CONCLUSIONS: Inflammatory
      factors contribute to anemia in renal patients in all stages of renal failure.
      High levels of neopterin in CKD patients suggest that neopterin contributes to
      impaired erythropoietin production and anemia in CKD patients.

PMID- 22997971
TI  - Evaluation of status of zinc, copper, and iron levels in biological samples of
      normal and arthritis patients in age groups 46-60 and 61-75 years.
AB  - BACKGROUND: A great number of studies have investigated the possible role of
      trace elements in the etiology and pathogenesis of rheumatoid arthritis (RA).
      METHODS: The aim of the study was to evaluate copper (Cu), iron (Fe), and zinc
      (Zn) levels in three biological samples (scalp hair, blood, and urine) in
      patients with rheumatoid arthritis (RA) in two groups, age ranges 46 - 60 and 61
      75 years, of both genders compared to age-matched healthy individuals. A
      microwave assisted wet acid digestion procedure was developed as a sample
      pretreatment for the determination of Cu, Fe, and Zn in biological samples. The
      digests of all biological samples were analysed for Cu, Fe, and Zn by flame
      atomic absorption spectrometry (FAAS) using an air/acetylene flame. The proposed
      method was validated by analyzing certified reference samples of hair, blood, and
      urine. RESULTS: The results indicated significantly lower levels of Fe, Cu, and
      Zn in the biological samples (blood and scalp hair) of male and female rheumatoid
      arthritis patients as compared to control subjects of both genders (p < 0.01).
      CONCLUSIONS: These data present guidance to clinicians and other professional
      investigating deficiency of essential trace metals in biological samples (scalp
      hair and blood) of RA patients.

PMID- 22997972
TI  - Influence of four different PTH methods on the classification of chronic kidney
      disease patients according to the new KDIGO guideline.
AB  - BACKGROUND: Secondary hyperparathyroidism develops frequently with chronic kidney
      disease (CKD) and is associated with poor outcome. The new CKD-MBD guideline,
      Kidney Disease: Improving Global Outcomes (KDIGO), recommends a target range for
      PTH which is based on the locally used, upper reference range limit (URL). We
      examined the impact of the KDIGO guideline on the classification of dialysis
      patients in two different hospitals using 4 different intact-PTH assays. METHODS:
      Blood samples from 76 consecutive hemodialysis CKD patients were measured for PTH
      concentration. Classification of the patients was performed according to the
      previous KDOQI and the KDIGO guideline using the manufacturers' and laboratory
      determined URLs. Classification of patients based on 3 different PTH methods
      (Siemens ADVIA Centaur, Siemens Immulite 2000, and Beckman Coulter Unicel DxI)
      was compared with the classification found in another hospital using the Roche
      Modular E170 PTH assay. RESULTS: Depending on the PTH assay used, between 9 (12%)
      to 14 (18%) of the patients were classified differently in the two hospitals if
      the KDOQI guideline was followed. Application of the KDIGO-PTH target range
      resulted in a similar or decreased number of differently classified patients if
      the PTH concentration was measured using the Advia Centaur and Immulite assays.
      With the Beckman Coulter PTH assay, however, the number of differently KDIGO
      classified patients increased if the manufacturers' URL (9.3 pmol/L) was used to
      calculate the PTH-target range. Application of the laboratory determined URL (7.0
      pmol/L) improved concordance in classification, although the number of
      differently classified patients was still higher than with the other PTH assays.
      The best concordance in classification for the Beckman Coulter assay was found at
      a PTH value of 6.0 pmol/L. Regarding the Roche and Siemens assays, no significant
      difference was found in the classification using the URL either determined by the
      laboratory or the manufacturers. CONCLUSIONS: Compared with the KDOQI guideline,
      the new KDIGO guideline may increase the number of discrepancies in the
      classification of CKD patients if the Access Beckman Coulter PTH assay is used in
      conjunction with the calculated target range based on the manufacturers' URL. The
      best concordance in the classification for the Beckman Coulter assay was found at
      a PTH value below the manufacturers' and laboratory determined URL.

PMID- 22997973
TI  - Comparison of three free T4 (FT4) and free T3 (FT3) immunoassays in healthy
      subjects and patients with thyroid diseases and severe non-thyroidal illnesses.
AB  - BACKGROUND: Free T4 (FT4) and free T3 (FT3) immunoassays exhibit wide inter-assay
      variations. We therefore established control values with three different
      immunoassays and compared their clinical performances in thyroidal diseases and
      severe/acute non-thyroidal illnesses (NTI). METHODS: The UniCel DxI 800,
      Architect i2000, and Elecsys 2010 assays were used. FT4 and FT3 reference ranges
      were established in 68 controls, without conditions interfering with thyroid
      function, with normal TSH (0.35-3.02 mU/L) and negative anti-thyroid peroxidase
      antibodies. Free hormones were determined in 60 patients with thyroid diseases
      (TSH: < 0.001-31.5 mU/L) and 45 NTI patients (TSH: 0.10-4.72 mU/L). Control
      values were normalized as Z-scores; patients' results were expressed as Z-scores,
      using the control values of each assay. Pairwise comparisons of the Z-scores were
      performed by Deming's regression. Classification of patients' results based on
      95% control values were evaluated by kappa agreement statistics. RESULTS: Control
      values for FT4 (pmol/L; geometrical means; 95% confidence intervals) were: 11.1
      (7.6-16.1), 12.3 (9.1-16.6), 15.6 (11.4-21.4) and for FT3: 4.8 (4.0-5.7), 4.0
      (3.0-5.3), 4.3 (3.1-5.09), with DxI 800, Architect, and Elecsys, respectively.
      Pairs of control Z-scores correlated significantly, but with different strengths
      (FT4: r = 0.915, 0.740, 0.770; FT3: r = 0.615; 0.589; 0.790, for DxI 800 vs.
      Elecsys; DxI 800 vs. Architect; Elecsys vs. Architect; p < 0.001); slopes and
      intercepts of paired controls were 1.00 and zero. In thyroid diseases, slopes of
      FT4 Z-scores among assays differed slightly from 1.00 (1.11, 0.88, 0.87 for DxI
      versus Elecsys, DxI 800 versus Architect, Elecsys versus Architect, respectively;
      p < 0.05); slopes of FT3 Z-scores were consistent with unity, except for DxI 800
      versus Elecsys (0.88; p < 0.05). In NTI patients, regression slopes were
      consistent with unity (p < 0.05). The agreement statistics showed moderate to
      very good inter-assay concordances for thyroid and NTI patients' results.
      CONCLUSIONS: FT4 and FT3 assays show moderate to very good agreement, in patients
      with thyroid diseases or NTI when compared pairwise to their control values.
      Slight quantitative differences between some pairs of assays are observed in
      thyroid diseases, after normalization as Z-scores.

PMID- 22997974
TI  - Investigation of the efficacy of a biogeneric recombinant human erythropoietin
      alfa in the management of renal anemia in patients on hemodialysis: a multi
      center clinical trial.
AB  - BACKGROUND: Recombinant human erythropoietin (rHuEPO) is the cornerstone therapy
      for anemia associated with chronic kidney disease. However, not all patients with
      renal anemia receive sufficient doses of rHuEPO due to its high cost. The present
      trial aimed to evaluate the efficacy of Epolyrec, a biogeneric rHuEPO, in the
      management of renal anemia in patients on hemodialysis. METHODS: Seventy-two
      patients with end stage renal disease (ESRD) who were receiving hemodialysis were
      assigned to receive Epolyrec subcutaneously at a dose of 40-80 IU/Kg in 2-3
      divided doses after each dialysis session for 12 weeks. Hemoglobin, hematocrit,
      and CBC/DIFF together with biomarkers of iron status, renal function, and trace
      elements were evaluated at baseline and during the course of trial. RESULTS:
      Hemoglobin concentrations and hematocrit progressively increased from baseline
      (8.45 +/- 1.42 mg/dL and 27.05 +/- 4.64% for hemoglobin and hematocrit,
      respectively) to the end of trial (10.56 +/- 1.93 and 34.06 +/- 6.70) (p <
      0.001). RBC count (p = 0.026), reticulocyte count (p = 0.045), and MCV (p <
      0.001) were also significantly increased at the end of trial (3.86 +/-
      0.91x10(6)/microL, 0.78 +/- 0.31%, and 93.50 +/- 10.90 fL for RBC count,
      reticulocyte count, and MCV, respectively) compared to baseline (0.98 +/- 3.38,
      0.18 +/- 0.63, and 89.75 +/- 9.35). Serum iron and ferritin were decreased while
      creatinine and phosphorous increased by the end of trial. No significant change
      was observed in WBC count, RDW, MCH, MCHC, BUN, PTH, Na, Ca, K, and Mg (p >
      0.05). The frequencies of evaluated side effects were generally low and < 10%.
      CONCLUSIONS: Epolyrec is clinically efficacious in the elevation of hemoglobin
      and hematocrit in anemic ESRD patients receiving hemodialysis. Future comparative
      trials are warranted to compare the efficacy and safety of Epolyrec to those of
      innovator products.

PMID- 22997975
TI  - Correlation of bone alkaline phosphatase and iPTH with some basic biochemical
      markers in predialysis and dialysis patients.
AB  - BACKGROUND: Bone alkaline phosphatase (BALP) is a direct and independent
      indicator of impaired bone turnover. We intended to find out whether there are
      any significant changes in BALP and iPTH levels, in comparison to total Ca, total
      Mg, inorganic P, total alkaline phosphatase (ALP), and tartrate resistant acid
      phosphatase (TRAP) in predialysis and dialysis patients. METHODS: Out of 266
      patients investigated, 114 were on continuous ambulatory peritoneal dialysis, 112
      were on maintenance haemodialysis, while 40 predialysis patients had end stage
      renal disease. The parameters were analysed according to the manufacturers'
      instructions. RESULTS: Correlations were established for the bone marker
      concentrations analysed among the studied groups. The largest ranges were
      determined for BALP and iPTH. Predialysis and dialysis patients showed very low
      levels of BALP. Dialysis patients had lower levels of iPTH (p < 0.001), while in
      predialysis patients the levels were significantly higher (p < 0.05) than
      recommended for low bone turnover, according to K/DOQI. CONCLUSIONS: The
      observations made in this study identify BALP as a good indicator of decreased
      bone turnover in predialysis and dialysis patients. However, in order to reveal a
      difference between bone activity and the level of parathyroid activity and its
      effect on bone turnover, it is always necessary to observe both BALP and iPTH
      levels.

PMID- 22997976
TI  - Levels of metalloproteinase (MMP-3, MMP-9), NF-kappaB ligand (RANKL), and nitric
      oxide (NO) in peripheral blood of osteoarthritis (OA) patients.
AB  - BACKGROUND: The aim of this study was to judge whether there is a correlation
      between some biochemical features of knee osteoarthritic blood and clinical
      characteristics and to evaluate the potential relationship between osteoarthitis
      (OA) severity and putative biomarkers for the disease. METHODS: 105 patients
      suffering from knee OA were analyzed clinically (Lequesne's index) and
      radiographically (Kellgren and Lawrence, K&L). Plasma and peripheral blood
      mononuclear cells (PBMC) were harvested separately. Specimens were analyzed for
      concentrations of nitric oxide (NO), matrix metalloproteinase-3 (MMP-3), and
      matrix metalloproteinase-9 (MMP-9). Transcript levels of the receptor activator
      of NF-kB ligand (RANKL) mRNA, MMP-3mRNA, and MMP-9mRNA were measured using real
      time quantitative RT-PCR. RESULTS: Data certified significantly increasing
      concentrations of plasma MMP-3, MMP-9, and NO as well as transcript levels of
      RANKL mRNA and MMP-9 mRNA in early OA (at grade I). There was a positive
      correlation of MMP-3 and MMP-9 content in plasma and MMP-9 mRNA expression levels
      in PBMC with the severity of clinical symptoms (total Lequesne's scores) in early
      OA. NO content in plasma correlated with total Lequesne's scores, pain scores in
      response to pressure, and swelling scores of early OA patients (atgGrade I).
      Analogously, there were positive correlations of RANKL mRNA expression with total
      Lequesne's scores, pain scores in response to pressure, and swelling scores in OA
      patients at Grade I. CONCLUSIONS: [corrected] Some biochemical factors, including
      content of NO, MMP-3, MMP-9, and transcript levels of some genes, including MMP-9
      mRNA and RANKL mRNA, may be specific and sensitive enough to diagnose OA diseases
      at an early stage in the pathological process of OA when radiological features do
      not reflect degradation of articular cartilage. Therefore, proper regulation of
      these factors may be a promising and realistic new target for the treatment of
      degenerative osteoarticular diseases.

PMID- 22997977
TI  - Dyslipidemia in the Greater Tunis population: prevalence and determinants.
AB  - BACKGROUND: Economic development and socio-demographic changes have led to
      increased frequency of cardiovascular disease and other chronic diseases in
      Tunisia. OBJECTIVES: To assess the prevalence of different types of dyslipidemia
      and to examine their association with sociodemographic characteristics in the
      Greater Tunis population. METHODS: The study included 2712 subjects (1228 men and
      1484 women) aged 35-70 years, recruited during the years 2004 and 2005 from the
      Greater Tunis population. Hypercholesterolemia, hypertriglyceridemia, and low HDL
      cholesterol were defined according to the National Cholesterol Education Program
      Adult Treatment Panel III. RESULTS: The prevalence of hypercholesterolemia,
      hypertriglyceridemia, and low HDL cholesterol was 40.8% (34.9% in males and 45.8%
      in females; p < 0.001), 29.2% (31.1% in males and 27.6% in females; p < 0.05),
      and 21.2% (32.5% in males and 11.5% in females; p < 0.001), respectively. The
      prevalence was higher in urban than rural regions. Hypercholesterolemia was more
      frequent in illiterate women and in men with high education level. CONCLUSIONS:
      Dyslipidemias are common in Tunisians, mainly in urban areas, in illiterate women
      as well as in men with high levels of education. Profound changes of life style
      and dietary habits of Tunisians are needed to reduce the risk of cardiovascular
      diseases.

PMID- 22997978
TI  - Endogenous hormones in postmenopausal females with breast cancer--before and
      after treatment.
AB  - BACKGROUND: Breast cancer is usually present for many years (as long as 5-10
      years) before it can be clinically diagnosed (theory of the 'dormant malignant
      cell'). This implies that breast cancer cells, during their subclinical period,
      are likely to have been exposed for a considerable time to endogenous sex
      hormones and endogenous hormonal milieu predicts the chances of breast cancer in
      females. So, we planned this study to evaluate the role of endogenous hormones in
      postmenopausal females excluding the patients on hormone replacement therapy as
      the relationship between breast cancer and hormone replacement therapy is well
      known. METHODS: Hormone therapy is known to affect these hormone levels but
      whether treatment of breast cancer per se also decreases the hormone levels is
      not known. We planned the present study to determine hormone levels in patients
      before and after 4 months of treatment (chemotherapy/surgery and radiotherapy).
      Circulating hormone levels were measured using a chemiluminescence method. Their
      results were compared with a group of 25 age matched healthy controls. RESULTS:
      We found that serum prolactin, testosterone and estrogen levels were very
      significantly higher in patients before treatment (Group I) as compared to
      controls (Group III). Serum prolactin and serum estrogen levels were
      significantly higher and serum testosterone was very significantly higher in
      patients before treatment (Group I) when compared after 4 months of treatment
      (Group II). Only serum estrogen levels were significantly high in patients after
      treatment (Group II) as compared to controls (Group III). Serum progesterone
      levels showed no significant difference to any of the groups. CONCLUSIONS: We
      concluded that postmenopausal females with breast cancer have abnormalities in
      hormone levels. These abnormalities may be considered in the pathogenesis of the
      disease and should be taken into account in the treatment of patients of breast
      cancer. It might also be helpful to delay the onset of cancer by normalizing the
      levels of these hormones and in deciding the treatment modality for the patients
      once breast cancer has been diagnosed but further studies are required to prove
      the benefit of measuring serum hormone levels as a screening test.

PMID- 22997979
TI  - Abnormal circulating levels of matrix metalloproteinases and their inhibitors in
      diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to determine plasma levels of matrix
      metalloproteinases (MMPs) 2, 3, and 9 and their tissue inhibitors (TIMPs) 1 and 2
      in type 2 diabetic patients (T2DM) compared to healthy subjects. METHODS: The
      study involved 54 patients with T2DM and 57 age and gender matched healthy adults
      as controls. MMPs 2 and 9 were analyzed by gelatin zymography and MMP-3 and TIMPs
      1 and 2 by ELISA. RESULTS: For technical feasibility, MMPs 2 and 9 were expressed
      in pro forms. Pro-MMP-9 was significantly higher (p < 0.05), whereas TIMP-1 and
      TIMP-2 levels were significantly decreased (p < 0.01) in patients with T2DM
      compared to controls. The MMP-3/TIMP-1 and the MMP-3/TMP-2 ratios were
      significantly higher in T2DM patients than controls (p < 0.05). Fasting plasma
      glucose was inversely correlated with TIMP-1 (r = -0.412, p < 0.01) and TIMP-2 (r
      = -0.315, p < 0.001), but was not associated with MMPs. CONCLUSIONS: The present
      study identified abnormalities in plasma markers for extracellular matrix
      metabolism in T2DM. The new parameters would constitute an effective approach to
      explore the complications of uncontrolled diabetes.

PMID- 22997980
TI  - Effects of the DPP-4 inhibitor, linagliptin, in diet-induced obese rats: a
      comparison in naive and exenatide-treated animals.
AB  - BACKGROUND: To assess the chronic effect of the DPP-4 inhibitor, linagliptin,
      alone, in combination with exenatide, and during exenatide withdrawal, in diet
      induced obese (DIO) rats. METHODS: Female Wistar rats were exposed to a cafeteria
      diet to induce obesity. Animals were then dosed with vehicle or linagliptin (3
      mg/kg PO) orally once-daily for a 28 day period. In a subsequent study, rats
      received exenatide (either 3 or 30 microg/kg/day) or vehicle by osmotic mini-pump
      for 28 days. In addition, groups of animals were dosed orally with linagliptin
      either alone or in combination with a 3 microg/kg/day exenatide dose for the
      study duration. In a final study, rats were administered exenatide (30
      microg/kg/day) or vehicle by osmotic mini-pump for eleven days. Subsequently,
      exenatide-treated animals were transferred to vehicle or continued exenatide
      infusion for a further ten days. Animals transferred from exenatide to vehicle
      were also dosed orally with either vehicle or linagliptin. In all studies, body
      weight, food and water intake were recorded daily and relevant plasma parameters
      and carcass composition were determined. RESULTS: In contrast to exenatide,
      linagliptin did not significantly reduce body weight or carcass fat in DIO rats
      versus controls. Linagliptin augmented the effect of exenatide to reduce body fat
      when given in combination but did not affect the body weight response. In rats
      withdrawn from exenatide, weight regain was observed such that body weight was
      not significantly different to controls. Linagliptin reduced weight regain after
      withdrawal of exenatide such that a significant difference from controls was
      evident. CONCLUSIONS: These data demonstrate that linagliptin does not
      significantly alter body weight in either untreated or exenatide-treated DIO
      rats, although it delays weight gain after exenatide withdrawal. This finding may
      suggest the utility of DPP-4 inhibitors in reducing body weight during periods of
      weight gain.

PMID- 22997981
TI  - Identification of spurious hemolysis in anticoagulated blood with Sysmex XE-2100
      and Siemens Advia 2120.
AB  - BACKGROUND: Various degrees of hemolysis might occur during collection,
      processing and storage of blood bags or blood tubes for hematological testing. In
      both circumstances, the identification of hemolysis is challenging since the
      centrifugation process is not required. The aim of this study was to identify
      simple hematological parameters that would help identify the presence of
      hemolysis in anticoagulated blood. METHODS: Twenty tubes containing K2EDTA
      anticoagulated blood were randomly selected from outpatient samples and divided
      in two aliquots. The former was immediately analyzed, whereas the latter was
      subjected to mechanical hemolysis by aspirating whole blood two times through a
      very fine needle to generate mechanical hemolysis. Both aliquots were tested on
      Advia 2120 and Sysmex XE-2100. RESULTS: The double aspiration of the blood
      through the fine needle caused a remarkable hemolysis with significant decrease
      of red blood cell (RBC) count (-17 +/- 11%; p < 0.01), hematocrit (-18 +/- 12%; p
      < 0.01) and reticulocytes (-24 +/- 13%; p < 0.01), but not of hemoglobin, white
      blood cell or platelet counts. A remarkable increase of immature platelet
      fraction (IPF) on XE-2100 and RBC ghosts on Advia 2120 was observed in the
      hemolyzed samples, whereas RBC fragments did not vary significantly. A
      significant correlation was also observed between hemolysis and reticulocyte
      count (r = 0.823; p < 0.01), IPF (r = -0.502, p = 0.024) and RBC ghosts (r = 
      0.711; p < 0.01). Receiver Operating Characteristic (ROC) curve analysis
      demonstrated a good performance of both IPF and RBC ghosts (i.e., AUCs 0.91 and
      0.96, respectively) for distinguishing non-hemolyzed from hemolyzed specimens.
      CONCLUSIONS: The absolute values of both IPF and RBC ghosts perform efficiently
      for distinguishing hemolyzed from non-hemolyzed specimens, although neither
      reached 100% sensitivity and specificity. Nevertheless, the demonstration that
      both parameters significantly increase after hemolysis can be reliably used to
      distinguish hemolyzed from non-hemolyzed blood.

PMID- 22997982
TI  - Biochemical association of hyperprolactinemia with hypothyroidism in infertile
      women.
AB  - BACKGROUND: To find out the incidence of hyperprolactinemia in infertile women
      and to find its correlation with hypothyroidism. METHODS: One hundred infertile
      women attending the out patient Department of Obstetrics and Gynaecology formed
      the subject matter of the study. Hormone levels of prolactin and thyroid
      stimulating hormone (TSH) were studied in all the subjects. The exclusion
      criterion was male factor infertility. Amongst the female factors leading to
      exclusion from the study were tubal factor, congenital abnormality of the
      urogenital tract, and any organic lesions. RESULTS: Of the one hundred infertile
      women, sixty (60%) had primary infertility and forty women (40%) had secondary
      infertility. Galactorrhea was present in 15% of the women. The incidence of
      hyperprolactinemia i.e. serum prolactin level > 15 ng/mL was 46%. Out of forty
      six, thirty women had primary infertility and sixteen women had secondary
      infertility. The mean serum prolactin level in hyperprolactinemic women was 79.40
      +56.59 ng/mL (range: 25.0-230.0 ng/mL). The mean serum prolactin level was not
      significantly different in the primary and secondary infertile group. The
      incidence of hypothyroidism in hyperprolactinemia was 28.26%. The mean serum TSH
      level in hypothyroid women with hyperprolactinemia was 32.06 +/- 23.00 (range:
      7.92-78.00 microIU/mL). The TSH level was not significantly different in primary
      and secondary infertile women. CONCLUSIONS: A high incidence of
      hyperprolactinemia was found in infertile women and a positive correlation was
      found between hyperprolactinemia and hypothyroidism.

PMID- 22997983
TI  - Delayed detection of cytomegalovirus-specific T-helper cells in a preterm infant
      following intrauterine exposure to tacrolimus.
AB  - After exposure to tacrolimus and CMV reactivation in utero, a preterm infant had
      a positive CMV polymerase chain reaction (PCR) in urine on day 2 of life. Naive T
      cells were reduced, but stimulation with CMV antigen and a polyclonal T-cell
      activator in vitro yielded no measurable CD4+ T-cell response. When repeated on
      day 30, polyclonal activation was in the range of healthy adults, while the
      immune response to CMV was incomplete with a lack of IFNgamma+ CD4+ T-cells and
      no anti-CMV IgM. Thus, exposure to tacrolimus in utero caused a transitional T
      cell activation defect which did not compromise viral clearance.

PMID- 22997984
TI  - Massive pericardial effusion with cardiac tamponade secundary to cholesterol
      pericarditis.
AB  - The presence of cholesterol crystals in the pericardial fluid is a very rare
      finding of unknown pathogenesis with no more than 100 reported cases in
      literature. Patients with cholesterol pericarditis usually have large volume
      spills of slow development that are well tolerated, rarely causing cardiac
      tamponade or constrictive pericarditis. We report a case of cholesterol
      pericarditis with a severe pericardial effusion and cardiac tamponade in a
      patient with an uncertain diagnosis of tuberculosis.

PMID- 22997985
TI  - Advantage of HbA1c assay by HPLC D-10 versus cobas integra 400 in a population
      carrier for HbS and HbC.
AB  - BACKGROUND: Several studies demonstrate significant bias in analytical methods
      used to measure glycohemoglobin. The clinical importance of that fact is evident
      when HbA1c overestimation leads to aggressive glucose management, resulting in
      more frequent hypoglycaemic episodes. Our study was aimed to compare two
      automated instruments (Integra 400 and D-10) in the evaluation of HbA1c in the
      Tunisian population. METHODS: Samples of 205 Tunisian diabetic patients were
      collected. The HbA1c assay was done simultaneously with a first generation
      immunoturbidimetric assay on an INTEGRA 400 (ROCHE) and using ionic exchange high
      pressure liquid chromatography (HPLC) on a D-10 system (BIO-RAD). RESULTS:
      Correlation is determined by linear regression analysis: D-10 = 0.921*(Integra
      400) +1.125; coefficient of correlation (r) = 0.946. This r increases to 0.973
      when samples of carriers for HbS and HbC (n = 9) are filtered out. For the
      carrier patients, significant differences in the percentage of HbA1c were
      observed relating to the methodology used. CONCLUSIONS: Laboratories must be
      aware of hemoglobin variant interferences on their methods of assessment of
      glycated hemoglobin. Using ion-exchange HPLC to control glycated hemoglobin seems
      to be essential to prevent mis-management in diabetic patients and to permit the
      diagnosis of the presence of HbS in patients.

PMID- 22997986
TI  - Rapid identification of heterozygous and homozygous hemoglobin constant spring by
      SYTO9 with a high resolution melting analysis.
AB  - BACKGROUND: Gel-electrophoresis and ethidium bromide are not ideally suited to
      large scale analysis in clinical laboratories. METHODS: Amplification refractory
      mutation system-polymerase chain reaction (ARMS-PCR) specific for Hb CS was
      performed in 10 blood samples from normal individuals and 61 samples containing a
      peak of Hb CS when analyzed by capillary electrophoresis. Heterozygosity of Hb CS
      was identified using SYTO9 and high resolution melting (HRM) analysis method.
      RESULTS: Specific peak heights of amplified fragments of wild type and Hb CS
      alleles were observed in the heterozygote. Only one peak height of amplified
      fragments of the wild type allele was observed in the normal individual while
      only one peak height of amplified fragments of Hb CS allele was observed in the
      homozygote. HRM analysis interpretation results were completely consistent with
      the interpretation results from gel-electrophoresis. CONCLUSIONS: SYTO9 HRM
      analysis may be used as an alternative for rapid diagnosis of heterozygosity of
      Hb CS.

PMID- 22997987
TI  - Human saliva total protein levels by AV17 pigment based analysis: validation,
      stability and short-term variation studies.
AB  - BACKGROUND: A colorimetric method based on acid violet pigment, namely AV17, to
      analyse salivary total protein content, was assessed. METHODS: Human saliva
      sample or standard (50 microL) was added to 1.5 mL of AV17 working solution (1
      mg/mL in 75 mmol/L sodium chloride and 1.7 mol/L phosphoric acid). Total protein
      concentration was measured at 546 nm. Salivary total protein of healthy subjects
      was analyzed. RESULTS: The standard protein was Human Serum Albumin and the
      detection range was 38 mg/L - 900 mg/L with a LOD and LOQ of 26 mg/L and 64 mg/L,
      respectively. Intraday CVs were 3% - 5% and interday CVs were 3%-6%. The dilution
      test demonstrated a correlation coefficient of 0.999 and the recovery tests
      ranged from 108% to 111%. Saliva sample stability was also demonstrated. No intra
      individual salivary total protein variation was found during the morning.
      CONCLUSIONS: The method suitability for laboratory diagnostic purposes to analyse
      human saliva protein content and stability was demonstrated.

PMID- 22997988
TI  - Increased fecal calprotectin in preterm infants with necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing entrocolitis (NEC) remains a potentially fatal disease in
      premature infants despite the recent advances in neonatal care. It is a disease
      with a multifactorial etiology leading to the one common final pathway of
      necrosis and inflammmation of the neonatal intestine. METHODS: Calprotectin is a
      calcium and zinc-binding protein in human neutrophils. Its concentration rises in
      various organic bowel diseases in adults and is resistant to degradation and has
      been proposed as a useful, simple, and rapid diagnostic method of inflammatory
      bowel disease that shows gastrointestinal inflammation in children and adults.
      RESULTS: We found that infants with necrotizing enterocolitis had increased fecal
      calprotectin concentrations, and there was a correlation between calprotectin
      concentrations and severity of NEC. CONCLUSIONS: We concluded that fecal
      calprotectin is a useful marker for diagnosis and severity of NEC in preterm
      infants.

PMID- 22997989
TI  - Utility of serum tartrate-resistant acid phosphatase isoform 5b, bone alkaline
      phosphatase and osteocalcin in osteoporotic fractures in Chinese patients.
AB  - BACKGROUND: The goal was to find out the clinical significances of tartrate
      resistant acid phosphatase isoform 5b (TRACP 5b), a biomarker of bone resorption,
      and bone alkaline phosphatase (BAP) and osteocalcin, two markers of bone
      formation, in evaluating the osteoporotic fracture risk in Chinese patients.
      METHODS: Thirty six Chinese osteoporotic fracture patients and 32 Chinese healthy
      subjects were included in the study. Bone mineral density (BMD) of lumbar spine
      and total body were determined by dual-energy X-ray absorptiometry in all
      subjects. Fasting blood samples were collected from all subjects and the serum
      concentrations of TRACP 5b, BAP, and osteocalcin were analyzed with enzyme-linked
      immunosorbent assay or immunoradiometric assay. RESULTS: With lower BMD, the
      osteoporotic fracture patients had elevated levels of TRACP 5b and BAP, compared
      with the healthy controls. No difference in serum osteocalcin level was observed
      between the fracture patients and the control. CONCLUSIONS: Elevated serum TRACP
      5b and BAP, combined with or without increased osteocalcin, are valuable tools
      for the assessment of osteoporotic fracture risk in Chinese patients.

PMID- 22997991
TI  - Significance of platelet most frequent volume for platelet size evaluation.

PMID- 22997990
TI  - Vitamin D status from dried capillary blood samples.
AB  - BACKGROUND: Given the huge impact of vitamin D deficiency on a broad spectrum of
      diseases such as rickets, osteoporosis, mineral bone disease-vascular
      calcification syndrome, infectious diseases, but also several types of cancer and
      CNS diseases, reliable and simple methods to analyze the vitamin D status are
      urgently needed. METHODS: We developed an easy technique to determine the 25-OH
      vitamin D status from dried blood samples on filter paper. This allows
      determination of the 25-OH vitamin D status independently of venous blood taking,
      since only sampling of capillary blood is required for this new method. We
      compared the results of vitamin D measurements from venous blood of 96 healthy
      blood donors with those from capillary blood taken from the same patients at the
      same time. The capillary blood was dried on filter paper using the D-Vital ID dry
      blood collection system. RESULTS: 25-OH vitamin D concentration data from
      extracted dried capillary blood filters correlated very well with data obtained
      after direct measurement of venous blood samples of the same blood donor (R:
      0.7936; p < 0.0001). The correlation was linear over the whole range of 25-OH
      vitamin D concentrations seen in this study. A Bland-Altman plot revealed good
      agreement between both tests. CONCLUSIONS: The D-Vital ID dry-blood collection
      system showed an excellent performance as compared to the classical way of 25-OH
      vitamin D measurement from venous blood. This new technique will facilitate easy
      and reliable measurement for vitamin D status, in particular, in rural or
      isolated areas, developing countries, and field studies.

PMID- 22997992
TI  - Assessment of variables affecting late left ventricular flow propagation
      velocity.
AB  - Early colour M-mode flow propagation velocity (Vpe) in the left ventricle is a
      well-known non-invasive index for assessing left ventricular relaxation. However,
      the utility and determinants of late colour M-mode flow propagation (Vpa) have
      received little attention to date. Vpa as a representation of the left
      ventricular vortex travelling velocity during late filling could have a distinct
      role in differentiating potential subgroups in diastolic failure. The aim of the
      present study was to establish the normal values of late flow propagation in a
      healthy population of various ages (18-79 years), and to examine the general and
      echocardiographic variables that affect Vpa. METHODS: We studied 75 apparently
      healthy subjects (age range, 18-79 years; 38 women, 37 men) as part of an
      outpatient clinic check-up screening. General parameters were recorded, including
      age, gender, height, weight, blood pressure, and heart rate. In addition,
      conventional grey-scale M-mode, 2D, as well as colour M-mode, 2D, and pulsed wave
      (tissue) Doppler echocardiographic parameters were obtained in a single centre
      and using a single operator setting. Backward linear regression analysis
      (dependent variable: Vpa) was performed to find the optimal model, taking into
      account multicollinearity and maximum coefficient of determination (R2). Due to
      the heteroscedasticity of the collected data, a logarithmic transformation was
      used. In addition, separate linear backward regression analysis was performed for
      the male and female subgroups. RESULTS: Vpa values were 26-179 cm/s. The optimal
      regression model after elimination included the following variables: age (beta =
      0.684, P < 0.001), height (beta = 0.521, P < 0.001), gender (beta = 0.343, P <
      0.05), left ventricular Vpe (beta = 0.299, P < 0.01), left ventricular posterior
      systolic (M-mode) wall thickness (beta = 0.288, P < 0.01), interventricular
      septum thickness diastole (beta = 0.346, P < 0.005), transmitral Doppler E-wave
      deceleration time apical 4-chamber (beta = -0.297, P < 0.05), and tissue Doppler
      peak E-wave mitral annulus (beta = 0.459, P < 0.005). The total coefficient of
      determination (R2) for this model was 0.540 (P < 0.001); 0.673 (P < 0.001) for
      men and 0.645 (P < 0.001) for women. CONCLUSION: Vpa, representing left
      ventricular vortex travelling velocity during late filling, shows a large range
      of values in normal healthy subjects. It is mainly depending on age, gender and
      left ventricular mass. Moreover, substantially different determinants are found
      between men and women. Further study is required to explore these findings.

PMID- 22997993
TI  - Muscular strength and diameter as determinants of aerobic power and aerobic power
      response to exercise training in CAD patients.
AB  - OBJECTIVE: Low exercise capacity and skeletal muscle strength are important
      predictors of all-cause mortality in healthy as well as diseased individuals.
      Compared to sedentary subjects, CAD patients have a decreased oxygen uptake
      (peakVO2) and show accompanying increased muscle fatiguability. Despite the known
      importance of oxygen extraction by peripheral muscles on improving peakVO2 and of
      the relationship between muscle strength and aerobic capacity, only few studies
      in CAD patients include measurements of muscle strength before and after cardiac
      rehabilitation. This study therefore aimed to evaluate how much of the variance
      in baseline peakVO2 and its response to exercise training can be explained by
      muscular parameters. METHODS: 260 CAD patients performed maximal incremental
      cycle ergometer testing and maximal knee muscle strength measurements. The rectus
      femoris diameter was measured using ultrasound. Zero order correlations were
      calculated and determinants of baseline and response in peakVO2 were analysed by
      multiple regression analysis. RESULTS: PeakVO2 and muscle strength and diameter
      increased significantly after three months of cardiac rehabilitation (P <
      0.0001). Zero order correlations showed significant correlations between muscular
      parameters and baseline peakVO2 (P < 0.0001). 63% of the total variance in
      baseline peakVO2 could be explained by seven parameters with knee extensor
      muscular endurance as the strongest predictor (P < 0.0001). 32% of the variation
      in relative increase in peakVO2 could be explained by 5 determinants of which the
      increase in muscular endurance was the strongest determinant (P < 0.0001).
      CONCLUSIONS: Knee extensor muscular endurance and its response after training are
      the strongest muscular predictors in explaining peakVO2 and its response in CAD
      patients.

PMID- 22997994
TI  - Extensive antiarrhythmic drugs after catheter ablation of persistent atrial
      fibrillation.
AB  - OBJECTIVE: Whether early rhythm suppression with extensive antiarrhythmic drugs
      (AADs) in persistent atrial fibrillation (AF) after catheter ablation decreases
      arrhythmia recurrence is unknown. We now report the 12-month follow-up data in
      this prospective and randomized study. METHODS AND RESULTS: 123 consecutive
      patients with persistent AF undergoing catheter ablation were randomly divided
      into an extensive AADs therapy group (group 1:62 patients using both class Ic and
      III AADs) or one AAD therapy group (group 2:61 patients using class Ic or III
      AADs alone) for the initial 2 months after ablation. Recurrence of atrial
      tachyarrhythmias (ATa) was valuated at both 2 months and 12 months following
      ablation. During the first 2 months after ablation, less ATa were found in group
      1 compared with group 2 (17/62 versus 29/61, P = 0.021). However, there was no
      difference with regard to ATa at 12 months between the groups (21/62 versus
      22/61, P = 0.799). ATa at 2 months and left atrial diameter (LAD) were the
      statistically significant predictors of ATa during 12-month follow-up.
      CONCLUSIONS: While use of extensive AADs within the initial 2 months after
      persistent AF ablation decreases early ATa, it does not prevent late ATa.
      Moreover, LAD as well as early ATa is a strong predictor of ATa at 12 months.

PMID- 22997995
TI  - Predictors of mid-term event-free survival in adults with corrected tetralogy of
      Fallot.
AB  - OBJECTIVES: Patients who underwent corrective surgery for tetralogy of Fallot
      (TOF) have increased long-term risk of cardiovascular morbidity and mortality.
      Yet, limited information is available on how to evaluate the risk in this
      population. Therefore, the aim of this study was to investigate the prognostic
      value of aerobic exercise capacity, along with other related parameters, at
      medium-term follow-up in adult patients with tetralogy of Fallot. METHODS AND
      RESULTS: Between 2000 and 2003, 92 adults (age 26.2 +/- 7.8 years; 63 male) with
      corrected TOF or TOF-type morphology underwent a cardiopulmonary exercise test
      (CPET) until exhaustion and echocardiography. During a mean follow-up of 7.3 +/-
      1.2 years (range 0.9 to 9.3 years), 2 patients died and 26 patients required at
      least 1 cardiac-related intervention at a mean age of 28.9 +/- 7.9 years. Event
      free survival tended to be higher in patients with the classical type of TOF (P =
      0.061). At multivariate Cox analysis, age at CPET [hazard ratio (HR): 1.13, P =
      0.006], age at correction (HR: 0.82, P = 0.037), right ventricular (RV) function
      (HR: 4.94, P = 0.001), QRS duration (HR: 1.02, P = 0.007), percentage of
      predicted peak oxygen uptake (peak VO2%) (HR: 0.96, P=0.029) and ventilatory
      efficiency slope (VE/VCO2 slope) (HR: 1.13, P = 0.021) were significantly related
      to the incidence of death/cardiac-related intervention during medium follow-up.
      CONCLUSIONS: Early corrective surgery and a well-preserved RV are associated with
      a better outcome in adults with corrected TOF. Furthermore, CPET provides
      important prognostic information; peak VO2% and VE/VCO2 slope are independent
      predictors for event-free survival in patients with corrected TOF.

PMID- 22997996
TI  - Three-dimensional speckle tracking echocardiography for the assessment of left
      ventricular function and mechanical dyssynchrony.
AB  - OBJECTIVE: Evaluation of left ventricular (LV) function and dyssynchrony is of
      vital importance. A newly-developed three-dimensional (3D) speckle tracking
      echocardiography (STE) has the potential to circumvent limitations of two
      dimensional STE. Our study was to evaluate LV function and dyssynchrony by 3D
      STE. METHODS AND RESULTS: Fifty-two non-ischaemic dilated cardiomyopathy patients
      (DCM) with complete left bundle-branch block and 55 healthy subjects were
      enrolled. Of these patients, 24 underwent cardiac resynchronization therapy
      (CRT). 3D-STE was performed before and 1 month after CRT. We measured 3D (3DS),
      longitudinal (LS), circumferential (CS) and radial (RS) strain of the LV. LV
      dyssynchrony was evaluated by the standard deviation of time to peak negative
      value of 3D strain (3DS-SD) and time to reach the minimum regional volume of 16
      segments (SDI) related to the heart cycle. DCM patients had significantly lower
      global 3DS (-17.12 +/- 6.70% vs -38.38 +/- 4.28%, P < 0.01), significantly
      greater 3DS-SD (11.11 +/- 5.14% vs 4.04 +/- 1.43%, P < 0.01) and SDI (9.69 +/-
      4.82% vs 4.23 +/- 1.33%, P < 0.01) than normal volunteers. 3DS, LS, CS, RS had an
      excellent correlation with LV ejection fraction (LVEF) (r2 = -0.94, -0.91, -0.93,
      0.89, respectively, P < 0.01 for all). 3DS-SD correlated well with SDI (ICC =
      0.85). For mild, moderate and severe systolic dysfunction, 3DS-SDs were 4.56 +/-
      1.53%, 9.87 +/- 2.58%, and 14.55 +/- 4.71%, respectively (P < 0.01) and SDIs were
      4.46 +/- 1.27%, 8.19 +/- 2.35%, and 12.83 +/- 4.87%, respectively (P < 0.01), but
      independently of QRS width. After CRT therapy, global 3DS (-13.12 +/- 2.63% to 
      14.06 +/- 2.53%, P = 0.025), 3DS-SDs (12.99 +/- 3.92% to 11.53 +/- 4.53%, P =
      0.015) and SDIs (10.85 +/- 3.74% to 9.50 +/- 4.63%, P = 0.013) were markedly
      improved. CONCLUSION: When image quality is optimal, 3D STE seems to be a
      promising approach assessing LV function and dyssynchrony.

PMID- 22997997
TI  - Secondary stroke prevention: misguided by guidelines?
AB  - OBJECTIVES: Despite large clinical trials, there is no consensus about the best
      antithrombotic strategy for the secondary prevention of non-cardioembolic
      ischaemic stroke.This retrospective study is the first to combine the results of
      the most important trials and to integrate data on study validity, effectiveness,
      adverse events, risk of non-compliance, and cost. METHODS: We searched MEDLINE,
      EMBASE, and the Cochrane Database (1996 to July 2011) and selected long-term
      secondary prevention trials with treatment with aspirin, dipyridamole,
      clopidogrel, aspirin plus dipyridamole, or aspirin plus clopidogrel. Subgroup
      analyses were included to explain differences in interpretations that could have
      led to the differences in guidelines. RESULTS: Two trials showed a small but
      significant reduction with aspirin plus dipyridamole compared to aspirin (ARR
      1.5%, P < 0.05 and ARR 1.0%, P < 0.05). There was no effect on vascular death.
      One trial showed a small but statistical significant reduction with clopidogrel
      compared to aspirin (ARR 0.5%, P < 0.05). The association of clopidogrel with
      aspirin could not show any significant benefit compared to clopidogrel
      monotherapy, nor compared to aspirin monotherapy, but showed higher rates of
      adverse events. Significantly more patients discontinued treatment with aspirin
      plus dipyridamole compared to aspirin monotherapy (34.5% versus 13.4% and 29.0%
      versus 22.2%, P < 0.001) and clopidogrel monotherapy (29.1% versus 22.6%, P <
      0.001). Transposition of statistical significant reductions in stroke recurrence
      into clinical significance could not be supported. CONCLUSIONS: Despite changes
      in international guidelines, aspirin monotherapy should retain its position as
      the main antiplatelet agent for secondary prevention of non-cardioembolic
      ischaemic stroke.

PMID- 22997998
TI  - A critical review on telemonitoring in heart failure.
AB  - Morbidity and mortality remain high in heart failure despite considerable
      progress achieved with medical therapy and electrical devices. A
      multidisciplinary approach is actually strongly recommended. In order to provide
      optimal care to the ever-growing population of patients with heart failure,
      telemonitoring has been proposed as a modality to improve usual care. The aim of
      this review is to provide an overview of the existing evidence on telemonitoring
      in HF. Despite two major meta-analyses with favourable results, two recent,
      large, multicentre, randomized controlled trials, one with a sophisticated
      technical remote telemonitoring approach (TIM-HF) in stable chronic HF and the
      other with a comprehensive telephone-based interactive voice-response monitoring
      (Tele-HF) in patients recently hospitalized for heart failure, have been
      performed and both failed to demonstrate a clinical benefit for telemonitoring.
      Newer technologies or other modalities, such as collaboration between a general
      practitioner and a heart failure clinic facilitated by telemonitoring should be
      further evaluated. Dedicated telemonitoring for heart failure may be a practical
      adjunct in selective centres and patients, on top of usual care, including
      education and a multidisciplinary approach. However, prior to being accepted as a
      standard of care, more evidence from large, randomized clinical trials is
      required.

PMID- 22997999
TI  - The prevalence and factors associated with aspirin resistance in patients
      premedicated with aspirin.
AB  - OBJECTIVE: Aspirin is a key drug used in treating patients with a high risk to
      develop stroke, myocardial infarction and other cardiovascular events. However, a
      considerable fraction of the patients develops aspirin resistance, which is a
      multi-factorial process that can occur due to patient's non-compliance, improper
      dosing, other co-morbidities or drug-drug interactions.This cross-sectional study
      was carried out to determine the prevalence and factors associated with aspirin
      resistance among Jordanians. METHODS: The study was performed on a sample of 418
      adult patients who were taking aspirin as an antiplatelet agent. To determine
      aspirin resistance, platelet function was assessed using a multiplate analyzer.
      RESULTS: Data shows that about 18.7% (78) of the patients were aspirin resistant.
      Aspirin resistance was associated with female gender (P < 0.05) and was higher
      among diabetic subjects (P < 0.05). Statins use was correlated with improved
      aspirin response (P < 0.05). No association was found between aspirin response
      and: age, body mass index, education, smoking status, family history of
      cardiovascular disease, aspirin dose and duration of aspirin use (P > 0.05). In
      addition, aspirin resistance was not related to parameters such as HbA1c and low
      density lipoprotein (LDL), comorbidities including dyslipidaemia, and
      hypertension, and concurrent use of other medications such as beta blockers,
      angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers
      (CCBs), and proton pump inhibitors (PPIs) (P > 0.05). CONCLUSION: The incidence
      of aspirin resistance is high in the Jordanian population. Aspirin resistance is
      associated with female gender and diabetes. On the other hand, the use of statins
      improves response to aspirin.

PMID- 22998000
TI  - Mother-offspring aggregation in home versus conventional blood pressure in the
      Tohoku Study of Child Development (TSCD).
AB  - OBJECTIVE: Few studies described the home blood pressure (HBP) in young children.
      Using intrafamilial correlations of blood pressure as research focus, we assessed
      the feasibility of HBP monitoring in this age group. METHODS: We enrolled 382
      mothers (mean age 38.8 years) and singletons (7.0 years) in theTohoku Study of
      Child Development.We measured their conventional blood pressure (CBP; single
      reading) at an examination centre. Participants monitored HBP in the morning. We
      used the OMRON HEM-70801C for CBP and HBP measurement. In a separate group of 84
      children (mean age 7.7 years), we compared blood pressure readings obtained by
      the OMRON monitor and the Dinamap Pro 100, a device approved by FDA for use in
      children. We used correlation coefficients as measure of intrafamilial
      aggregation, while accounting for the mothers' age, body mass index, heart rate
      and smoking and drinking habits and the children's age, height, and heart rate.
      RESULTS: Mother-offspring correlations were closer (P < or = 0.003) for HBP than
      CBP for systolic pressure [0.28 (P < 0.0001) vs 0.06 (P = 0.26)] and diastolic
      pressure [0.28 (P < 0.0001) vs 0.02 (P = 0.65)].The between-device differences
      (OMRON minus Dinamap) averaged 7.8 +/- 6.0 mmHg systolic and 5.8 +/- 5.5 mmHg
      diastolic. CONCLUSIONS: HBP monitoring is an easily applicable method to assess
      intrafamilial blood pressure aggregation in young children and outperforms CBP.
      Validation protocols for HBP devices in young children need revision, because the
      Korotkoff method is not practicable at this age and there is no agreed
      alternative reference method.

PMID- 22998001
TI  - Right and left atrial appendage function in patients with atrial septal aneurysm
      without patent foramen ovale.
AB  - AIM: Atrial septal aneurysm (ASA) is a risk factor for arterial embolism. Despite
      prior reports concerning paradoxical embolism through a patent foramen ovale,
      atrial dysfunction and atrial arrhythmias might represent an additional mechanism
      for arterial embolism.The aim of this study was to evaluate right and left atrial
      appendage contractilty in patients with ASA. METHODS AND RESULTS: A total of 30
      patients with ASA (10 males/20 females, mean age 50.2 +/- 15.3 years) and 30
      controls (12 males/ 18 females, mean age 47.7 +/- 10 years) were included.
      Conventional transthoracic and multiplane transoesophageal echocardiography were
      performed in patient and control groups. Flow and myocardial velocity were
      measured in both atrial appendages. Baseline characteristics of both groups were
      comparable. Flow velocity and myocardial contraction velocity in both atrial
      appendages were significantly lower in ASA patients. Compared to the control
      group, patients with ASA had a larger length, base and area of both appendages.
      CONCLUSION: In ASA patients right and left atrial appendage function are
      impaired. Biatrial dysfunction may cause arrhythmia and thromboembolism.

PMID- 22998002
TI  - Ictal asystole: case report with review of literature.
AB  - Cardiac arrhythmias are frequently observed during epileptic seizures. Mostly
      they are benign, but severe bradycardia and asystole occur in 0.27-0.5% of
      patients who have seizures on video-EEG monitoring units. Especially patients
      with partial seizures involving the insular, orbital frontal and anterior
      temporal lobe regions, are at risk. Ictal bradycardia could be a cause of SUDEP
      (sudden unexpected death in epilepsy) and pacemaker insertion might therefore
      improve survival in selected cases, although more research is needed to prove
      this. We present a case of prolonged ictal asystole in a patient with newly
      diagnosed partial epilepsy originating from the temporal lobe.

PMID- 22998003
TI  - Acute myocardial infarction in early postpartum.
AB  - We present a case of acute anterior myocardial infarction in a breastfeeding
      woman, 10 days after delivery. The presumed cause was proximal left anterior
      artery vasospasm, induced by a combination of smoking a first cigarette in the
      early morning and salbutamol inhalation, in the particular context of peripartum.
      We discuss briefly the epidemiology, pathophysiology, risk factors, diagnosis,
      treatment and prognosis of myocardial infarction related to pregnancy and the
      postpartum period.

PMID- 22998004
TI  - Alcohol and drugs: twins or evil in a young heart.
AB  - We describe how the use of multiple drugs and excessive alcohol intake caused a
      dilated cardiomyopathy complicated by cardiogenic shock and life-threatening
      ventricular arrhythmias in an otherwise healthy young man. The diagnosis was made
      by exclusion of other causes of cardiomyopathy. Surprisingly an ischaemic scar
      without significant coronary artery disease was also found on cardiac MRI, most
      likely related to vasoactive drugs (cocaine). An ICD was implanted during the
      same hospital stay after careful assessment of the risk of recurrent ventricular
      arrhythmias and sudden cardiac death.

PMID- 22998005
TI  - Implantation of a fully subcutaneous ICD in a patient with single ventricle
      morphology and Eisenmenger physiology.
AB  - Implantable cardioverter-defibrillator (ICD) therapy has been adopted
      increasingly in congenital heart disease. However, in patients with intracardiac
      right-to-left shunting the use of standard transvenous ICD lead systems is
      relatively contraindicated due to the increased risk of systemic thromboembolism.
      In this constellation, a recently introduced totally subcutaneous ICD system (S
      ICD) seems to be a good and minimal invasive alternative to conventional
      epicardial ICD therapy. Here we describe the first use of this S-ICD in a patient
      with single ventricle and Eisenmenger physiology. In this unusual cardiac anatomy
      modification of the standard implantation technique by use of short sequences of
      fluoroscopy helped to ensure exact electrode and can placement and thus regular
      function of the S-ICD system.

PMID- 22998006
TI  - Paradoxical coronary embolism, a rare cause of acute myocardial infarction on
      positive pressure ventilation.
AB  - A 65-year-old man developed respiratory failure and was admitted to the Intensive
      Care Unit for positive pressure ventilation and antibiotic and antifungal
      therapy.There was a sudden deterioration with chest pain, worsening hypoxia and
      hypotension. Serial electrocardiograms showed new onset right bundle-branch block
      with developing anterior ST-segment elevation. An urgent coronary angiogram
      revealed acute occlusion of the left anterior descending artery with a single
      large distinct thrombus, which was successfully removed with an aspiration
      catheter. A presumptive diagnosis of paradoxical coronary embolus was made. A
      short review is provided of this relatively rare clinical entity which has the
      potential to present in intensive care patients who have an underlying intra
      cardiac defect and require positive pressure ventilation. This case emphasises
      the importance of being aware of less common causes of acute clinical
      deterioration and electrocardiographic changes in the ventilated patient.

PMID- 22998007
TI  - Electrophysiological findings in Fabry cardiomyopathy: mapping the maze of risk
      stratification.
AB  - We report a case of Anderson-Fabry disease in a young man presenting with cardiac
      hypertrophy and asymptomatic non-sustained ventricular tachycardia. The patient
      was referred for evaluation of implantable cardioverter/defibrillator therapy.
      Assessment of left ventricular ejection fraction is considered the gold standard
      for identifying patients at risk of sudden cardiac death. However, this patient's
      left ventricular function was preserved. Electrophysiological study did not
      reveal inducible arrhythmia or cardiac conduction abnormalities. Review of the
      literature indicates limited knowledge on the electrophysiology of Fabry
      cardiomyopathy and highlights the need for optimized risk stratification
      strategies.

PMID- 22998008
TI  - Use of electroanatomic voltage mapping to guide lead implantation in young adults
      with congenital heart disease.
AB  - Lead implantation in young adults with congenital heart disease is often
      problematic due to the reduction in the number of surgical access routes and
      consequent scar tissue formation related to previous surgery. In such a
      situation, anatomic and electromagnetic voltage mapping of the heart may be
      useful to find the optimal implantation site for sensing and pacing activities.

PMID- 22998009
TI  - Intractable hypotension and myocardial ischaemia induced by co-ingestion of
      ethanol and disulfiram.
AB  - We report a case of a 42-year-old woman who presented with intractable
      hypotension and non-ST-elevation myocardial infarction as a result of a
      disulfiram-ethanol reaction. During hypotension and ischaemic ECG changes we
      assessed cardiac function by echocardiography. Aggressive intravenous fluid
      resuscitation was unsuccessful. Only after starting intravenous norepinephrine,
      blood pressure and ECG normalized. Coronary angiography performed three days
      after admission was normal. Cardiovascular adverse events are a known,
      potentially fatal complication of concomitant ingestion of ethanol and
      disulfiram, but only few cases are reported in literature. Cardiologists and
      emergency care physicians should be aware of this interaction when a patient with
      chronic alcohol abuse presents with severe hypotension or myocardial ischaemia.

PMID- 22998010
TI  - Apical hypertrophic cardiomyopathy: elegant use of contrast-enhanced
      echocardiography in the diagnostic work-up.
AB  - A 69-year-old woman was evaluated for chest pain complaints. The ECG demonstrated
      sinus rhythm with deep negative T waves from V2 to V6, in l, aVL and the inferior
      leads.Transthoracic echocardiography (TTE) showed suboptimal image quality and
      was nondiagnostic. A repeat TTE study after administration of an echo contrast
      agent showed normal contractile function with apical hypertrophy. This report
      contains two messages. First, contrast-enhanced echocardiography is an elegant
      bedside tool to assess left ventricular apical segments. Secondly, in patients
      with ECG repolarisation abnormalities without an obvious ischaemic cause, routine
      echocardiography without contrast may not exclude apical HCM. Definitive
      exclusion of this important diagnosis requires further imaging such as CMR or
      contrast echocardiography.

PMID- 22998012
TI  - Detection of trace nitroaromatic isomers using indium tin oxide electrodes
      modified using beta-cyclodextrin and silver nanoparticles.
AB  - The determination of nitroaromatic compounds in aqueous solution was investigated
      at beta-cyclodextrin (beta-CD)/silver nanoparticle (AgNPs) composite modified ITO
      electrodes. This method relies on the different reduction potentials for the
      various nitroaromatic isomers, the different binding strengths of the
      nitroaromatic isomer guests to the beta-CD host, and excellent electron transfer
      ability of AgNPs. After incubation in a solution with different single
      nitroaromatic compounds, reduction peaks in the range from -550 to -913 mV were
      observed at the modified electrode, depending on the nitroaromatic compound
      present. The sensor exhibited selectivity for some isomers in a solution
      containing a mixture of nitroaromatic compounds. In particular, the sensor shows
      specificity for 4-nitroaniline and 1-chloro-2-nitrobenzene over other
      nitroaniline isomers and nitrochlorobenzene isomers, respectively. The results
      show that all the nitroaromatic compounds, 2-nitroaniline, 3-nitroaniline, 4
      nitroaniline, 1-chloro-2-nitrobenzene, 1-chloro-3-nitrobenzene, and 1-chloro-4
      nitrobenzene, could not only be detected but the electrode demonstrated a
      preference for the more strongly complexing species.

PMID- 22998011
TI  - Circulating cytokine pattern and factors describing rheumatoid arthritis: IL-15
      as one of the biomarkers for RA?
AB  - The aim of study was to examine relationship among levels of cytokines (IL-6, IL
      13, IL-15, TNF-alpha) and chemokine (IL-8), production of autoantibodies,
      radiographic progression, and factors describing rheumatoid arthritis (RA). A
      total of 156 RA patients according to ACR criteria, and 55 control subjects were
      recruited into study. We observed higher levels of IL-15 within RA patients
      compared to healthy controls. Correlations among cytokine levels and the measures
      of rheumatoid factors, anti-CCP, measures of disease activity, and radiographic
      progression were observed. We conclude that IL-15 level in circulation could
      serve as one of the biomarkers for RA detection.

PMID- 22998013
TI  - Impact of different distribution scenarios and recommended storage conditions on
      flavor related quality attributes in ripening fresh tomatoes.
AB  - Tomato (Solanum lycopersicum) fruits of three cultivars picked at different
      ripening stages were subjected to conditions in the laboratory simulating both
      short and long distribution chains as occurring in commercial practice and to
      recommended storage conditions. At the end of the postharvest experiments, a
      flavor quality profile of fruits was obtained by chemical determination of
      volatile compounds, sugars, and organic acids, and physical measurement of
      texture properties. In two of the three cultivars, the overall profile and many
      of the individual quality attributes was significantly affected by the
      distribution chain conditions, the effect being more pronounced in tomatoes
      marketed at full ripeness than in those marketed at an intermediate ripening
      stage. In these cultivars, tomatoes harvested at the Breaker stage, subjected to
      long chain conditions and then allowed to achieve full ripeness at room
      temperature, did not develop the same overall profile observed on fruits fully
      ripened on the vine and exposed to a simulated short chain. Fruits subjected to
      recommended commercial storage conditions, cold stored above the chilling range
      (10 or 13  degrees C) and at high relative humidity (95%), developed a different
      profile when compared to fruit exposed to the simulated long distribution chain
      (6  degrees C and 55-80% RH), suggesting that these changes in temperature and
      relative humidity may remarkably affect flavor formation in tomato fruits. Major
      drivers of profile differentiation between tomatoes subjected to different
      postharvest scenarios were the levels of some aroma compounds derived from
      aminoacids (1-nitro-2-phenylethane, 2-isobutylthiazole, phenylacetaldehyde, 2
      phenylethanol, and 2- and 3-methylbutanal) and lipids ((E,E)- and (E,Z)-2,4
      decadienal), and, among nonvolatile flavor compounds, of organic acids (citric
      and malic).

PMID- 22998014
TI  - Plasma transfusion in liver transplantation: a randomized, double-blind,
      multicenter clinical comparison of three virally secured plasmas.
AB  - BACKGROUND: The clinical equivalence of plasma treated to reduce pathogen
      transmission and untreated plasma has not been extensively studied. A clinical
      trial was conducted in liver transplant recipients to compare the efficacy of
      three plasmas. STUDY DESIGN AND METHODS: A randomized, equivalence, blinded trial
      was performed in four French liver transplantation centers. The three studied
      (fresh-frozen) plasmas were quarantine (Q-FFP), methylene blue (MB-FFP), and
      solvent/detergent (S/D-FFP) plasmas. The primary outcome was the volume of plasma
      transfused during transplantation. Secondary outcomes included intraoperative
      blood loss, hemostasis variables corrections, and adverse events. RESULTS: One
      hundred patients were randomly assigned in the MB-FFP, 96 in the S/D-FFP, and 97
      in the Q-FFP groups, respectively. The median volumes of plasma transfused were
      2254, 1905, and 1798 mL with MB-FFP, S/D-FFP, and Q-FFP, respectively. The three
      plasmas were not equivalent. MB-FFP was not equivalent to the two other plasmas,
      but S/D-FFP and Q-FFP were equivalent. The median numbers of transfused plasma
      units were 10, 10, and 8 units with MB-FFP, S/D-FFP, and Q-FFP, respectively.
      Adjustment on bleeding risk factors diminished the difference between groups: the
      excess plasma volume transfused with MB-FFP compared to Q-FFP was reduced from
      24% to 14%. Blood loss and coagulation factors corrections were not significantly
      different between the three arms. CONCLUSION: Compared to both Q-FFP and S/D-FFP,
      use of MB-FFP was associated with a moderate increase in volume transfused,
      partly explained by a difference in unit volume and bleeding risk factors. Q-FFP
      was associated with fewer units transfused than either S/D-FFP or MB-FFP.

PMID- 22998015
TI  - Open-heart surgery increases cerebrospinal fluid levels of Alzheimer-associated
      amyloid beta.
AB  - BACKGROUND: Neurocognitive dysfunction occurs frequently after open-heart
      surgery. It has been suggested that cognitive decline after cardiac surgery with
      cardiopulmonary bypass (CPB) could be a functional consequence of Alzheimer's
      disease (AD)-like neuropathological changes. The aim of the present study was to
      evaluate the cerebrospinal fluid (CSF) levels of amyloid beta peptide (Abeta(1
      42) ) and soluble fragments of amyloid precursor protein (sAPP) as well as the
      cerebral inflammatory response to open-heart surgery. METHODS: Ten patients
      undergoing aortic valve replacement with CPB were included. CSF was obtained the
      day before and 24 h after surgery for assessment of CSF levels of Abeta(1-42) 
      alpha-cleaved sAPP and beta-cleaved sAPP (sAPP-beta). Furthermore, CSF and serum
      levels of the inflammatory cytokines: tumour necrosis factor alpha (TNF-alpha),
      interleukin-6 (IL-6) and interleukin-8 (IL-8) were also assessed. RESULTS:
      Cardiac surgery with CPB increased CSF levels of Abeta(1-42)  from 447 +/- 92 to
      641 +/- 83 ng/l (P = 0.011), while CSF levels of sAPP-beta decreased from 276 +/-
      35 to 192 +/- 21 ng/ml (P = 0.031). CSF levels of TNF-alpha increased from <=
      0.60 to 0.79 +/- 0.26 ng/l (P = 0.043), IL-6 from 1.89 +/- 0.53 to 22.8 +/- 6.9
      ng/l (P = 0.003) and IL-8 from 39.8 +/- 7.8 to 139 +/- 18.3 ng/l (P < 0.001).
      CONCLUSIONS: Cardiac surgery with CPB causes a profound cerebral inflammatory
      response, which was accompanied by increased post-operative CSF levels of the AD
      biomarker Abeta(1-42) . We hypothesize that these changes may be relevant to
      Alzheimer-associated amyloid build-up in the brain and cognitive dysfunction
      after cardiac surgery with CPB.

PMID- 22998016
TI  - Biodegradable hyperbranched polyglycerol with ester linkages for drug delivery.
AB  - Biodegradable hyperbranched polyglycerols (dHPGs) were synthesized through
      oxyanionic initiating hybrid polymerization of glycerol and glycidyl
      methacrylate. Due to the introduction of ester linkages into the hyperbranched
      polyglycerol backbone, dHPGs showed good biodegradability and low cytotoxicity.
      Benefiting from the existence of terminal hydroxyls and methacryloyl groups, both
      the anticancer drug methotrexate (MTX) and fluorescent probe Rhodamine-123 could
      be conjugated onto the surface of dHPGs easily. The resultant MTX-conjugated
      polymers (dHPG-MTXs) exhibited an amphiphilic character, resulting in the
      formation of micelles in an aqueous solution. The release of MTX from micelles
      was significantly faster at mildly acidic pH of 5.0 compared to physiological pH
      of 7.4. dHPG-MTX micelles could be efficiently internalized by cancer cells. MTT
      assay against cancer cells showed dHPG-MTXs micelles had high anticancer
      efficacy. On the basis of their good biodegradability and low cytotoxicity, dHPGs
      provide an opportunity to design excellent drug delivery systems.

PMID- 22998017
TI  - Introducing the bio-psycho-social-physical model of dementia through a collective
      case study design.
AB  - AIMS AND OBJECTIVES: To provide evidence for the development of a physical domain
      attached to the well-known bio-psycho-social model of dementia. The objectives
      were to develop a set of international case studies that followed a trajectory
      approach, from prevention to end-of-life care. BACKGROUND: In the UK the bio
      psycho-social model has informed the shape of the National Institute for Health
      and Clinical Excellence and the Social Care Institute for Excellence 'dementia'
      guideline. However, limited attention has been paid to outlining and describing a
      physical domain of dementia, a discrepancy that informed the rationale for this
      study. DESIGN: A collective case study design was used to address the research
      aim and objectives. METHODS: Case studies from along the trajectory of dementia
      were provided by an international team of contributors from an inter-disciplinary
      background comprising nursing (general and mental health), social work and social
      science. RESULTS: The team's synthesis and analysis of the six case studies
      generated five repeating themes with each theme becoming components of a
      'physical' domain of dementia. The five identified physical components were: (1)
      physical well-being, (2) physical health and examination, (3) physical care, (4)
      physical treatment and (5) physical environment. CONCLUSIONS: The development of
      a bio-psycho-social-physical model of dementia presents a holistic and culturally
      sensitive approach to understanding the experience of living with dementia, and
      to providing care and support in a variety of situations and contexts. RELEVANCE
      TO CLINICAL PRACTICE: The physical domain of dementia has particular relevance to
      nursing and nursing practice, such as providing physical care at the end-of-life.
      The interplay between the biological-psychological-social-physical domains of
      dementia and the trajectory of dementia could form the basis of clinical decision
      making and practice.

PMID- 22998018
TI  - Palladium(II)-catalyzed oxidative C-H/C-H coupling and eliminative S(N)(H)
      reactions in direct functionalization of imidazole oxides with indoles.
AB  - Two novel synthetic approaches to realize the direct C(sp(2))-H bond
      functionalization in cyclic nitrones are reported. Palladium(II)-catalyzed
      oxidative C-C coupling of 2,2-dialkyl-4-phenyl-2H-imidazole 1-oxides with indoles
      was shown to result in the formation of 5-indolyl-3-yl derivatives, while
      nucleophilic substitution of hydrogen (S(N)(H)) at C(5) of the same imidazole
      system was found to afford the corresponding deoxygenated compounds.

PMID- 22998019
TI  - Aliskiren attenuates chronic carbon tetrachloride-induced liver injury in mice.
AB  - BACKGROUND: Increased angiotensin II (Ang II) plays an important role in liver
      inflammation and fibrogenesis. Chronic administration of aliskiren, a newly
      developed direct renin inhibitor, decreases Ang II in the hypertensive patients
      and animals. AIMS: Our study aims to evaluate the possible protective effects of
      chronic administration of aliskiren in a chronic liver injury model. METHODS:
      C57BL6 mice were injected intraperitoneally with carbon tetrachloride (CCl(4)) to
      induce chronic liver injury. The injured mice were randomly assigned to aliskiren
      treated (25 mg/kg per day for 2 weeks, the CCl(4) + Ali group) or untreated group
      (the CCl(4) group). Mice without CCl(4) and aliskiren administration served as
      the normal control. RESULTS: In the CCl(4)-injured mice, aliskiren attenuated
      liver inflammation and fibrosis. The levels of hepatocyte apoptosis, lipid
      peroxidation production, the activation of hepatic stellate cells and Kupffer
      cells, hepatic expression of p47 phox, inflammatory mediators and profibrotic
      markers were reduced in the CCl(4) + Ali group. Furthermore, aliskiren decreased
      Ang II, activated the renal expression of renin, but down-regulated the hepatic
      expression of renin and renin receptor in the CCl(4)-injected mice. CONCLUSIONS:
      Aliskiren attenuates chronic liver injury in the CCl(4)-treated mice by reducing
      Ang II. Direct renin inhibition may serve as a potential treatment for chronic
      liver injury.

PMID- 22998020
TI  - Ba(1-x)Na(x)Ti2Sb2O (0.0 <= x <= 0.33): a layered titanium-based pnictide oxide
      superconductor.
AB  - A new layered Ti-based pnictide oxide superconductor, Ba(1-x)Na(x)Ti(2)Sb(2)O
      (0.0 <= x <= 0.33), is reported. X-ray studies revealed that it crystallizes in
      the tetragonal CeCr(2)Si(2)C structure. The undoped parent compound,
      BaTi(2)Sb(2)O [P4/mmm; a = 4.1196(1) A; c = 8.0951(2) A], exhibits a charge
      density wave (CDW)/spin density wave (SDW) transition at 54 K. Upon chemical
      doping with Na, the CDW/SDW transition is systematically suppressed, and
      superconductivity arises with the critical temperature (T(c)) increasing to 5.5
      K. Bulk superconductivity was confirmed by resistivity, magnetic, and heat
      capacity measurements. Like the high-T(c) cuprates and the iron pnictides, the
      superconductivity in BaTi(2)Sb(2)O arises from an ordered state. Similarities and
      differences between BaTi(2)Sb(2)O and the cuprate and iron pnictide
      superconductors are discussed.

PMID- 22998021
TI  - Click-chemistry as a mix-and-match kit for amphiphile synthesis.
AB  - A small library of amphiphilic compounds was synthesized in an array using the
      Huisgen 1,3-dipolar cycloaddition of terminal alkynes with azides (CuAAC or click
      reaction). The self-assembling properties of these compounds were evaluated by
      polarizing microscopy and synchrotron small-angle X-ray scattering analysis. 

PMID- 22998022
TI  - HIV-associated fatigue in the era of highly active antiretroviral therapy: novel
      biological mechanisms?
AB  - OBJECTIVE: The aim of the study was to determine the prevalence and risk factors
      for HIV-associated fatigue in the era of highly active antiretroviral therapy
      (HAART). METHODS: A cross-sectional survey of 100 stable HIV-infected out
      patients was carried out. Severity of fatigue was measured using the Fatigue
      Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were
      evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected
      patients were compared with those for 166 uninfected controls and 74 patients
      with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy)
      (ME). RESULTS: Ninety-one per cent of HIV-infected patients were on HAART and 78%
      had suppressed plasma HIV viral load (<= 40 HIV-1 RNA copies/mL). Fifty-one per
      cent of HIV-infected patients reported excessive symptomatic fatigue (FIS >= 40),
      and 28% reported severe fatigue symptoms (FIS >= 80). The mean FIS score among
      HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0
      (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P <
      0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV
      infected patients, fatigue severity was not significantly associated with current
      or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior
      dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of
      clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue.
      Additionally, fatigue severity correlated strongly with symptomatic orthostatic
      intolerance (r = 0.65; P < 0.001). CONCLUSIONS: Fatigue is very common and often
      severe in HIV-infected out-patients, despite viral suppression and good immune
      function. In a subgroup of patients, prior d-drug exposure may contribute to
      fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue
      associated with HIV infection, as in other chronic diseases, and CFS/ME, and
      should be further evaluated with the potential for a shared therapeutic approach.

PMID- 22998023
TI  - Bordetella holmesii bacteremia in a renal transplant recipient: emergence of a
      new pathogen.
AB  - Bordetella holmesii is a gram-negative rod that was initially identified in 1995.
      It causes bacteremia, pneumonia, and endocarditis mostly in patients with
      anatomical or functional asplenia. We report here, to the best of our knowledge,
      the first case of B. holmesii bacteremia in a renal transplant recipient
      following rituximab therapy for recurrence of membranoproliferative
      glomerulonephritis.

PMID- 22998024
TI  - The detrimental effect of nitric oxide on tissue is associated with inflammatory
      events in the vascular endothelium and neutrophils in mice with dextran sodium
      sulfate-induced colitis.
AB  - Nitric oxide (NO) is thought to be a key molecule in the progression of
      ulcerative colitis and experimental colitis induced by dextran sodium sulfate
      (DSS). However, the detrimental effect of DSS-induced NO production on the
      colonic mucosa is incompletely understood. Increases in the expression of
      adhesion molecules in the vascular endothelium and activated neutrophils (thereby
      releasing injurious molecules such as reactive oxygen species) are reportedly
      associated with the pathogenesis of DSS-induced colitis. We investigated if the
      detrimental effect of NO production on the colonic mucosa was attributable to the
      activation of neutrophil infiltration by NO in mice with DSS-induced colitis.
      NO(2)(-)/NO(3)(-) content in the middle and distal colon was increased on days 5
      and 7, but alterations in the proximal colon were not observed. Myeloperoxidase
      (MPO) activity and expression of P-selectin and intercellular adhesion molecule-1
      (ICAM-1) were significantly increased in the entire colon, whereas TNF-alpha
      levels were significantly increased only in the middle and distal colon on day 7.
      The pathology of colitis and increases in colonic MPO activity, P-selectin, ICAM
      1, and TNF-alpha levels were suppressed by the inducible NO synthase (iNOS)
      specific inhibitor aminoguanidine and NO scavenger c-PTIO, whereas all but TNF
      alpha levels were increased by the non-specific NOS inhibitor L-NAME. These
      findings suggest that iNOS-derived NO increases TNF-alpha levels in the middle
      and distal colon and increased TNF-alpha levels induce expression of P-selectin
      and ICAM-1, thereby promoting the infiltration of activated neutrophils, which
      leads to damage to colonic tissue.

PMID- 22998025
TI  - Efficacy of liposomal amphotericin B for prophylaxis of acute or reactivation
      models of invasive pulmonary aspergillosis.
AB  - The efficacy of antifungal prophylaxis for prevention of invasive aspergillosis
      (IA) may depend on whether IA results from recent inhalation of spores or
      reactivation of latent colonisation. Compare the efficacy of liposomal
      amphotericin B (LAmB) for prophylaxis in acute and reactivation models of IA. In
      the acute model, mice immunosuppressed from day 0 were challenged at day 3 with
      an aerosol of Aspergillus fumigatus. LAmB (15 mg kg(-1) ) was administered at day
      0 or at challenge. In the reactivation model, naive mice exposed to A. fumigatus
      remained untreated until clearance of spores from the lungs, then
      immunosuppressed to induce reactivation. A single LAmB dose was administered at
      start of immunosuppression. In the acute model, a single administration of LAmB
      at start of immunosuppression was not effective, but an additional administration
      resulted in a significant decrease in lung fungal burden (P < 0.05 vs. controls).
      A significant prophylactic efficacy was observed when LAmB was administered once
      at challenge (P < 0.01). In the reactivation model, a single LAmB administration
      at start of immunosuppression significantly reduced both reactivation rate and
      fungal burden vs. controls (P < 0.01). Our results show that the conditions under
      which IA develop and timing of administration of LAmB were determinant variables
      for prophylactic efficacy.

PMID- 22998026
TI  - Women's experiences of important others in a pregnancy dominated by intimate
      partner violence.
AB  - BACKGROUND: Being exposed to intimate partner violence (IPV) during pregnancy is
      a difficult and complex situation. Despite this, there are few studies describing
      women's own needs for help and support. AIM: The aim of this study is to gain a
      deeper understanding of women's experiences of important others in relation to
      changing their life situation in a pregnancy dominated by IPV. METHODS: The study
      has a qualitative phenomenological design. The data were collected through in
      depth interviews with seven Norwegian women, who were exposed to IPV during
      pregnancy. FINDINGS: Being pregnant and exposed to violence in relation to
      important others means confronting present life, life history and future life.
      The essence implies striving for control in an uncontrolled situation, where
      other people might be experienced as both a rescuer and a risk. This is further
      described in four constitutions: the child needs protection; my mother is always
      present for me; an exhausted run for help; and a reduced, but important social
      network. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: For women exposed to
      violence, pregnancy can offer an opportunity for change. Midwives play a unique
      role in relation to care and continuity in this phase of life, as they can
      support pregnant women, help to identify their needs, possibilities for action
      and advise them about appropriate services. Midwives can encourage and support
      women to find people whom they can trust and who can offer assistance. It is
      vital that midwives ask about the women's relationship to the baby and their
      social networks, especially the relationship with their mothers. Ethical
      considerations:  During the whole study process, guidelines for research on
      violence against women were followed, to respect the integrity, security and
      confidentiality of the participants. The study is ethically approved.

PMID- 22998027
TI  - Right ventricular injury due to displaced sternal wire.

PMID- 22998028
TI  - Bloom syndrome: report of two cases in siblings.

PMID- 22998029
TI  - The effect of topical bevacizumab as an adjunctive therapy for corneal
      neovascularization.

PMID- 22998030
TI  - Role of specific cations and water entropy on the stability of branched DNA motif
      structures.
AB  - DNA three-way junctions (TWJs) are important intermediates in various cellular
      processes and are the simplest of a family of branched nucleic acids being
      considered as scaffolds for biomolecular nanotechnology. Branched nucleic acids
      are stabilized by divalent cations such as Mg(2+), presumably due to condensation
      and neutralization of the negatively charged DNA backbone. However, electrostatic
      screening effects point to more complex solvation dynamics and a large role of
      interfacial waters in thermodynamic stability. Here, we report extensive computer
      simulations in explicit water and salt on a model TWJ and use free energy
      calculations to quantify the role of ionic character and strength on stability.
      We find that enthalpic stabilization of the first and second hydration shells by
      Mg(2+) accounts for 1/3 and all of the free energy gain in 50% and pure MgCl(2)
      solutions, respectively. The more distorted DNA molecule is actually destabilized
      in pure MgCl(2) compared to pure NaCl. Notably, the first shell, interfacial
      waters have very low translational and rotational entropy (i.e., mobility)
      compared to the bulk, an entropic loss that is overcompensated by increased
      enthalpy from additional electrostatic interactions with Mg(2+). In contrast, the
      second hydration shell has anomalously high entropy as it is trapped between an
      immobile and bulklike layer. The nonmonotonic entropic signature and long-range
      perturbations of the hydration shells to Mg(2+) may have implications in the
      molecular recognition of these motifs. For example, we find that low salt
      stabilizes the parallel configuration of the three-way junction, whereas at
      normal salt we find antiparallel configurations deduced from the NMR. We use the
      2PT analysis to follow the thermodynamics of this transition and find that the
      free energy barrier is dominated by entropic effects that result from the
      decreased surface area of the antiparallel form which has a smaller number of low
      entropy waters in the first monolayer.

PMID- 22998031
TI  - Electrocorticographic evidence of perituberal cortex epileptogenicity in tuberous
      sclerosis complex.
AB  - OBJECT: Tuberous sclerosis complex (TSC) is a multisystem autosomal dominant
      disorder resulting in hamartomas of several organs. Cortical tubers are the most
      prominent brain lesions in TSC. Treatment-resistant epilepsy often develops early
      in life in patients with TSC and is associated with severe intellectual and
      behavioral impairments. Seizures may remit following epilepsy surgery in selected
      cases, yet it remains unclear whether the tuber or the perituberal cortex is the
      source of seizure onset. In this study, the authors reviewed the onset of
      seizures in patients in whom depth electrodes had been placed within or adjacent
      to cortical tubers. METHODS: After obtaining institutional review board approval,
      the authors retrospectively reviewed data from 12 pediatric patients with
      multifocal TSC and treatment-resistant epilepsy who had undergone invasive
      intracranial electroencephalographic monitoring. Tubers were identified on
      postimplantation MRI, and all depth electrodes were located. Depth electrode
      contacts were classified visually as either tuber/perituberal cortex or
      nontuber/nonperituberal cortex. Board-certified clinical neurophysiologists
      reviewed the seizures to identify all electrodes involved in the ictal onset.
      RESULTS: Among 309 recorded seizures, 104 unique ictal onset patterns were
      identified. Of the 11 patients with electrodes recording in a tuber, 9 had
      seizure onsets involving the tuber. Similarly, of the 9 patients with perituberal
      recording electrodes, 7 had perituberal ictal onsets. Overall, there was no
      difference in the percentage of contacts involved in seizure onset between the
      tuber and perituberal cortex. In a subset of 7 patients in whom at least 1 depth
      electrode contact was within the tuber and 1 was in the perituberal cortex, there
      was no difference between the percentage of tuber and perituberal onsets.
      CONCLUSIONS: Findings demonstrated heterogeneity in the ictal onset patterns as
      well as involvement of the tuber and perituberal cortex within and between
      patients. Although the data are limited by the restricted region(s) sampled with
      intracranial electrodes, they do suggest that cortical hyperexcitability in TSC
      may derive from the tuber or surrounding cortex.

PMID- 22998032
TI  - Recurrent meningeal sarcoma successfully treated with stereotactic radiosurgery.
AB  - Primary intracranial meningeal sarcoma is a rare neurological malignancy without
      strong evidence-based treatment guidelines. The authors describe a boy with
      primary meningeal sarcoma who symptomatically presented at 10 months of age and
      was treated with primary resection. The patient had multifocal recurrence
      approximately 2 years later. Given the location and rapid progression of the
      disease, the boy was treated with gamma knife surgery. He had a complete
      radiographic response 3 years posttreatment. He attends school full time and
      enjoys good quality of life. Based on local control and response to radiosurgery,
      the authors suggest that multifocal meningeal sarcomas not amenable to resection
      can be effectively managed with stereotactic radiosurgery.

PMID- 22998033
TI  - Intrathecal baclofen therapy--how we do it.
AB  - Intrathecal baclofen has become an invaluable tool to treat spasticity of various
      etiologies. Children who benefit from intrathecal baclofen are often
      significantly underweight due to underlying disease pathology, and they lack
      adequate soft-tissue mass to effectively provide cover to the pump. Thus, in this
      population, subfascial implantation is favored over the subcutaneous technique in
      view of the high frequency of wound dehiscence and subsequent explantation of the
      pump associated with the latter method.   The authors describe and review their
      unit's adapted subfascial implantation technique that has been performed over a
      period of 10 years in 182 children. This technique provides better tissue
      coverage for the pump and has resulted in lowering the risk of complications as
      compared with the subcutaneous technique.

PMID- 22998034
TI  - Hysteresis of haptic vertical and straight ahead in healthy human subjects.
AB  - BACKGROUND: The subjective haptic vertical (SHV) task requires subjects to adjust
      the roll orientation of an object, mostly in the roll plane, in such a way that
      it is parallel to perceived direction of gravity. Previously we found a tendency
      for clockwise rod rotations to deviate counter-clockwise and vice versa,
      indicating hysteresis. However, the contributing factors remained unclear. To
      clarify this we characterized the SHV in terms of handedness, hand used,
      direction of hand rotation, type of grasping (wrap vs. precision grip) and
      gender, and compared findings with perceived straight-ahead (PSA). Healthy
      subjects repetitively performed adjustments along SHV (n = 21) and PSA (n = 10)
      in complete darkness. RESULTS: For both SHV and PSA significant effects of the
      hand used and the direction of rod/plate rotation were found. The latter effect
      was similar for SHV and PSA, leading to significantly larger counter-clockwise
      shifts (relative to true earth-vertical and objective straight-ahead) for
      clockwise rotations compared to counter-clockwise rotations irrespective of the
      handedness and the type of grip. The effect of hand used, however, was opposite
      in the two tasks: while the SHV showed a counter-clockwise bias when the right
      hand was used and no bias for the left hand, in the PSA a counter-clockwise bias
      was obtained for the left hand without a bias for the right hand. No effects of
      grip and handedness (studied for SHV only) on accuracy were observed, however,
      SHV precision was significantly (p < 0.005) better in right-handed subjects
      compared to left-handed subjects and in male subjects. CONCLUSIONS: Unimanual
      haptic tasks require control for the hand used and the type of grip as these
      factors significantly affect task performance. Furthermore, aligning objects with
      the SHV and PSA resulted in systematic direction-dependent deviations that could
      not be attributed to handedness, the hand used, or the type of grip. These
      deviations are consistent with hysteresis and are likely not related to
      gravitational pull, as they were observed in both planes tested, i.e. parallel
      and perpendicular to gravity. Short-term adaptation that shifts attention towards
      previous adjustment positions may provide an explanation for such biases of
      spatial orientation in both the horizontal and frontal plane.

PMID- 22998035
TI  - Secretory sorting receptors carboxypeptidase E and secretogranin III in amyloid
      beta-associated neural degeneration in Alzheimer's disease.
AB  - The secretory sorting receptors carboxypeptidase E (CPE) and secretogranin III
      (SgIII) critically activate peptidic messengers and targeting them at the
      regulated secretory pathway. In Alzheimer's disease (AD), the wide range of
      changes includes impaired function of key secretory peptidic cargos such as brain
      derived neurotrophic factor (BDNF) and neuropeptides. Here, we analyzed CPE and
      SgIII in the cerebral cortex of AD patients and transgenic mice. In the normal
      human cortex, a preferential location in dendrites and perikarya was observed for
      CPE, whereas SgIII was mainly associated with axons and terminal-like buttons.
      Interestingly, SgIII and CPE were consistently detected in astroglial cell bodies
      and thin processes. In AD cortices, a strong wide accumulation of both sorting
      receptors was detected in dystrophic neurites surrounding amyloid plaques.
      Occasionally, increased levels of SgIII were also observed in plaque associate
      reactive astrocytes. Of note, the main alterations detected for CPE and SgIII in
      AD patients were faithfully recapitulated by APPswe/PS1dE9 mice. These results
      implicate for the first time the sorting receptors for regulated secretion in
      amyloid beta-associated neural degeneration. Because CPE and SgIII are essential
      in the process and targeting of neuropeptides and neurotrophins, their
      participation in the pathological progression of AD may be suggested.

PMID- 22998036
TI  - A reaction-based sensing scheme for gold species: introduction of a (2
      ethynyl)benzoate reactive moiety.
AB  - To alleviate side reactions identified in an N-propargyl-rhodamine lactam sensing
      system, we devised the novel reaction-based sensing scheme for gold species based
      on the alkynophilicity. A fluorescein (2-ethynyl)benzoate underwent Au(III)
      promoted ester hydrolysis selectively over other metal ions with high
      sensitivity, which accompanies a turn-on fluorescence change in pH 7.4 HEPES
      buffer. The work offers a versatile reactive moiety for the development of gold
      probes with improved sensing properties.

PMID- 22998037
TI  - The making of an education day in a canadian health care facility.
AB  - The benefits of an education day have been documented within a variety of
      disciplines; however, there is a paucity of up-to-date knowledge on the
      implementation and planning phases, and these phases are addressed in this
      article. Having knowledge of what form of delivery education can take can affect
      employer-provided education throughout health care. This article will benefit
      staff development educators by addressing issues in staff development and the
      role that an education day can have in health care facilities.

PMID- 22998038
TI  - Teaching evidence-based practice using a mock trial.
AB  - The mock trial, which is an educational tool used in many different professions,
      is a scripted form of debate that teaches the critical thinking process. Using
      the mock trial approach, two nurse educators at one medical center taught nursing
      staff and students the major elements of evidence-based practice. The verdict to
      be decided in the trial was whether family-witnessed resuscitation should be used
      in practice. This article outlines the steps taken to carry out this endeavor.
      Nursing faculty can use this mock trial approach to teach a variety of concepts
      in nursing education.

PMID- 22998039
TI  - An overview of Turkish folk medicine; past and present.
AB  - Plants have become a unique source for the mankind either as food or medicine. No
      doubt this relationship initiated instinctively to satisfy the inner man, while
      later they noticed the healing potential of plants. This had been the beginning
      point of traditional medicines worldwide. Among the ca. 300.000 plant species
      have been identified on the earth so far, only a fraction (ca.120.000) has been
      reported to be used as food or remedy. The remaining part has still waited for
      discovery of their beneficial effects on human health. The metabolite composition
      of the plants has attracted the scientific community rather than plants itself.
      However, random screening of plants for potential health benefits without any
      evidence is a tedious task. Investigation planning based on the traditional use
      of plants has become one of the solutions to overcome this problem. Thenceforth
      1985 increasing numbers of scientific field surveys have been conducted
      throughout Turkey for the documentation of folkloric utilization of plants
      against disease symptoms. However, due to the impact of modernization in society
      accessibility of reliable information has become problematic day-by-day.
      Moreover, increasing number of migrations from rural areas to urban to improve
      the living conditions makes difficult to find informants in countryside. In order
      to rescue this valuable information before complete vanishing, several
      alternative survey techniques have been attempted. In this study, reports on
      Turkish folk medicine which have been conducted so far will be evaluated. Based
      on the data obtained, past and present situations will be discussed.

PMID- 22998040
TI  - New therapeutic platforms for the treatment of epithelial and cutaneous lesions.
AB  - There are still so-called unmet needs in the treatment of epithelial and
      cutaneous lesions. Mucositis, ocular lesions, chronic skin wounds represent
      typical examples. These pathologies do not yet afford a satisfactory treatment.
      In particular chronic wounds represent a major health care burden, likely to
      increase as the population ages. Healing of epithelial and cutaneous lesions
      progresses through a complex cascade of events starting with the secretion in the
      local environment of a pool of growth factors, cytokines and proteins from the
      serum and degranulating platelets. Recently platelet lysate (PL), a
      hemoderivative obtained by platelet destruction by freeze-thawing of a platelet
      rich plasma (PRP) sample in the presence of an anticoagulant agent, has proved
      capable of promoting the healing of buccal and corneal lesions. Since the
      efficacy of growth factors (GFs) critically depends on the way they are made
      available to the injured tissue, the development of suitable therapeutic vehicles
      is of paramount importance to release GFs according to the repairing
      requirements. The present work focuses on the development and testing of few such
      formulations, in particular a mucoadhesive gel and an in situ gelling buccal
      spray for the treatment of oral mucositis, and a thermosensitive eye drop
      solution for corneal lesions. Besides technological characterization, the
      formulations have been preliminarily screened with an ELISA assay, a cell
      proliferation test and an in vitro wound healing test. Some formulations have
      been used in early clinical trials.

PMID- 22998041
TI  - Nanoparticle targeting to inflamed tissues of the gastrointestinal tract.
AB  - Dose limitations in therapy induced by adverse effects due to unselective drug
      availability are a common problem. One prominent example for this dilemma are
      inflammatory diseases of the gastrointestinal tract. The challenge for drug
      delivery systems in the therapy of these diseases is the delivery of the active
      ingredient to the site of inflammation. Colloidal carriers allow to improve
      delivery of drugs to the site of action and appear promising to overcome this
      general therapeutic drawback. Here we focus on nanocarrier-based drug delivery
      strategies for the treatment of common inflammatory disorders like inflammatory
      bowel disease and gastric ulcer.

PMID- 22998042
TI  - Phenotyping and genotyping of drug metabolism to guide pharmacotherapy in
      psychiatry.
AB  - In psychiatry, around 130 drugs are available which have been detected and
      developed during the last 60 years. These drugs are effective and essential for
      the treatment of many psychiatric disorders and symptoms. Therapeutic outcomes,
      however, are still far from satisfactory for many patients. One major reason
      underlying insufficient response or problems of tolerability or toxicity is
      considerable interindividual variability in the pharmacokinetic properties of the
      patients. At the exact same dose, a more than 20-fold interindividual variation
      in steady state concentrations of the drugs in the body may result. Patients
      differ in their ability to absorb, distribute, metabolize and excrete drugs due
      to concurrent disease, age, concomitant medication or genetic peculiarities. A
      valuable tool for tailoring the dosage of the prescribed medication(s) to the
      individual characteristics of a patient is therapeutic drug monitoring (TDM). For
      a considerable number of psychopharmacologic compounds, TDM has become a clinical
      routine for dose adjustment. The benefits of TDM regarding optimization of
      psychopharmacotherapy can be further enhanced by genotyping of cytochrome P450
      enzymes (CYP). These enzymes are highly polymorphic and involved in the
      metabolism of most psychotherapeutic drugs. Genotyping related information may be
      supportive especially for drugs that are predominantly metabolized by CYP2C19 or
      CYP2D6. The in vivo activity of CYP isoenzymes can be determined using probe drug
      assays. When used appropriately, phenotyping and genotyping methods are most
      helpful for problem solving and improvement of the outcomes of
      psychopharmacotherapy for many patients.

PMID- 22998043
TI  - M-protein-derived conformational peptide epitope vaccine candidate against Group
      A Streptococcus.
AB  - Identification of the most relevant epitopes is the initial challenge of peptide
      based vaccine design. Chimeric conserved epitopes of the Group A Streptococcus
      (GAS) M-protein were used in the development of an anti-GAS vaccine candidate.
      Previously, these epitopes have incorporated a GCN4 peptide from yeast to
      maintain their native helical structure. Here, we designed a new peptide epitope
      based on the minimal B-cell epitope from GAS M-protein. This new epitope was able
      to adopt the desired helical conformation without the need for the foreign GCN4
      flanking sequence. The selected epitope induced significant immune responses upon
      administration with external adjuvant, and when incorporated into the Lipid Core
      Peptide (LCP) system. Moreover, the antibodies produced against this epitope were
      able to recognize the native p145 sequence from M-protein.

PMID- 22998044
TI  - Beta3-adrenoreceptors in cardiovasular diseases: new roles for an "old" receptor.
AB  - Beta3-adrenoreceptors (B3AR) are traditionally known as metabolic receptors in
      adipose tissue, but came into focus in the cardiovascular field after our
      demonstration of their expression in human cardiac myocytes and endothelial
      cells, where they mediate endothelium-dependent relaxation of coronary resistance
      vessels through production of both nitric oxide and endothelium-dependent
      hyperpolarization factor(s) (EDHF). B3AR are also expressed at the plasma
      membrane of rodent and human cardiac myocytes. Notably, their expression is
      increased in several forms of human cardiomyopathies, which raises questions
      about their adaptive or maladaptive role in myocardial remodelling. To test the
      hypothesis that they may counteract the adverse effect of B1-B2-AR
      overactivation, we set out to study the cardiac phenotype of transgenic mice
      expressing human recombinant B3AR under the cardiac-specific alpha-MHC promoter.
      While exhibiting no apparent phenotype at basal state, these mice seem protected
      from hypertrophic remodeling under a variety of stresses, without developing left
      ventricular dysfunction. Notably, this protection seems to depend on a functional
      nitric oxide synthase (NOS), as it is abrogated under NOS inhibition. These
      features can all be recapitulated in homotypic cardiac myocytes cultures in
      vitro. B3AR transgenic mice may also be protected from fibrosis through a
      paracrine cross-talk to cardiac fibroblasts. These data suggest a beneficial role
      of B3AR in myocardial remodeling through attenuation of fibrosis and of excessive
      cardiac myocyte hypertrophy, while at the same time optimizing perfusion. As B3AR
      are resistant to homologous desensitization, they are attractive targets for
      therapeutic interventions in the setting of chronic sympathetic stimulation, as
      it is prevalent in heart failure and several cardiomyopathies.

PMID- 22998045
TI  - Midkine in inflammatory and toxic conditions.
AB  - Midkine (MK) is a member of midkine family which is composed of MK and
      pleotrophin (PTN). MK behaves like a cytokine and growth factor, promotes the
      proliferation, differentiation, survival, adhesion, migration of cells. MK
      expression usually increases during ischemia, inflammation, tissue repair,
      neoplastic transformation and in different toxic conditions. Immune cells and
      most of organs have MK secretion function in fetal and adult life. MK could be a
      promising prognostic/diagnostic marker and a potential target in many of diseases
      including malignancy, toxic and inflammatory diseases. This review focuses on
      both cell protective and immune-modulatory roles of MK in different in vitro and
      in vivo disease models and human reports. MK is still a novel molecule in the
      regulation of organ development and the etiology of many diseases.

PMID- 22998046
TI  - Chemical phosphorylation of histidine residues in proteins using potassium
      phosphoramidate -- a tool for the analysis of acid-labile phosphorylation.
AB  - Histidine (His)-phosphorylation is labile at low pH and has therefore not been in
      the focus of proteomic analysis in the past although a few single-case studies
      have been performed. The systematic investigation of model substances generates
      confidence in experimental procedures and allows determining their limits. In
      order to extend earlier peptide studies to His-phosphoproteins and elucidate
      their behavior and recovery in proteomic procedures, potassium phosphoramidate
      (PPA) was used to generate model proteins, which were subsequently exposed to gel
      electrophoresis, enzymatic digest and mass spectrometry based protein analysis.
      Myoglobin having eleven His-residues was highly phosphorylated by PPA showing a
      distribution of modified protein forms with four phosphate-carrying His-residues
      in the most abundant species. Since myoglobin is a heme-binding protein it was
      additionally indicated that synthetic phosphorylation may retain protein folding
      targeting only structurally accessible His-residues. Insulin, betacasein and
      cytochrome C were phosphorylated on their His-residues and the corresponding
      peptides were detected in protein digest mixtures and in background of
      tryptically digested Escherichia coli lysate. In gel electrophoresis protocols,
      lengthy procedures at low pH such as staining reduced recovery. Synthetic
      phosphorylation of proteins and peptides with PPA allows the generation of
      suitable standard compounds for the systematic optimization of analytical
      protocols. All tested proteins responded to PPA treatment, partially even
      preserving tertiary structure. A distribution of modified protein forms was
      generated which could be subjected to further separation to isolate the fully
      phosphorylated species.

PMID- 22998047
TI  - Melatonin and synthetic analogs as antioxidants.
AB  - Recent studies suggest that overproduction of reactive oxygen and nitrogen
      species (ROS/RNS), lowered antioxidant defense of the body. Oxidative stress is
      damaging to DNA, lipids, proteins and many more vital macromolecules.
      Consequences of oxidative stress thought to contribute to the development of a
      wide range of diseases including Alzheimer's disease, Parkinson's disease,
      diabetes, rheumatoid arthritis, neurodegeneration in motor neuron diseases and
      many cancer types. Melatonin (MLT) is a powerful antioxidant with a particular
      role in the protection of nuclear and mitochondrial DNA. To find an improved
      antioxidant activity, developments of novel synthetic analogues are under
      investigation. These studies may offer a new progress and approach in antioxidant
      drug development as well as antioxidant chemistry. Therefore, we have been
      synthesizing novel MLT derivatives and investigating their antioxidant
      capacities. This review gives a brief knowledge about the MLT based analogue
      indole derivatives as potential antioxidants.

PMID- 22998048
TI  - Problem based pharmacotherapy teaching for pharmacy students and pharmacists.
AB  - Pharmacy profession also involves identifying, solving and preventing drug
      related problems, as well as encouraging proper use of medications, thus
      improving clinical outcome of the treatment. Pharmacotherapy is usually thaught
      as lectures in pharmacy schools and many students have a difficulty in
      implementing the theoretical knowledge into practice. Therefore courses on
      "rational drug use or rational pharmacotherapy" should be given by problem based
      teaching methods. Since 2009, "Rational Drug Use" courses are given in Marmara
      University School of Pharmacy by such a method (based on simulated patients and
      dispensing score) developed by the 'Turkish Pharmacological Society'. The method
      enables problem based learning and it is also used in some of the pharmacy
      schools in Turkey and in Near East University in Northern Cyprus. This kind of
      learning will provide ability for critical thinking, improve problemsolving
      skills and decision making during pharmacotherapy.

PMID- 22998049
TI  - Cheap, suitable, predictable and manageable nanoparticles for drug delivery:
      quantum dots.
AB  - Recently ZnO quantum dots are reported to be very promising for drug delivery. It
      has also been reported that adsorptive material can deliver drug molecules by
      simple adsorption and they release the drug at site of action by subsequent
      desorption. This has been shown for carbon nanotubes and some other hydrophobic
      molecules for transdermal applications in the literature. Therefore it was aimed
      to find the effect of ZnO quantum dots on transdermal penetrations of selected
      model drug molecules (ketoprofen and dexketoperofen). Drug coated ZnO quantum
      dots were found to increase transdermal penetration of ketoprofen and
      dexketoprofen through rat skin.

PMID- 22998050
TI  - Analysis of carcinogenic Polycyclic Aromatic Hydrocarbons (PAHS): an overview of
      modern electroanalytical techniques and their applications.
AB  - A number of Polycyclic Aromatic Hydrocarbons (PAHs) have been shown to be
      toxicants, and induce carcinogenic and immunotoxic effects. Since PAHs are often
      present in low concentrations and it may be difficult to determine them in
      complex matrices, it is therefore essential to use powerful analytical tools to
      separate and identify the analyses in the samples. In this paper, initially, a
      short description of the principles, instrumentation, and use of common
      extraction and analytical techniques for PAH pollutants and their metabolites
      will be made in light of the previously reported works and major reviews. Special
      attention will be given to the use of modern polarographic and voltammetric
      techniques on the mercury and different types of solid electrodes, together with
      their some practical applications. The main drawbacks and limitations of these
      methods will also be discussed.

PMID- 22998051
TI  - Design, development and evaluation of chronomodulated drug delivery systems of
      amoxicillin trihydrate with enhanced antimicrobial activity.
AB  - The present studies entail the formulation development and evaluation of
      chronomodulated drug delivery system of amoxicillin trihydrate (AMT), which
      comprises of a bilayer tablet containing a delayed release and a sustained
      release layer. Direct compression method was employed for the preparation of
      bilayer matrix tablets containing rational blend of polymers, such as Eudragit
      L100 D55 as delayed release polymer and HPMCK4M, HPMCK15 and HPMCK100 are
      sustained release polymers. In- vitro drug release studies of bilayer tablets
      observed a good sustained release action with time-dependent burst release after
      a lag-time of 3 hrs. Evaluation of drug release kinetics from sustained release
      layer of bilayer tablets followed Higuchi model via quasi-Fickian diffusion
      mechanism. SEM studies revealed formation of pores on sustained release layer,
      which confirmed the drug release through diffusion and predominantly by surface
      erosion mechanism. Evaluation of antimicrobial activity showed a decrease in
      minimum inhibitory concentration of optimized bilayer tablets vis-a-vis
      conventional marketed formulation. Accelerated stability studies revealed that
      the optimized bilayer tablet formulation was found to be stable upto the period
      of 6 months. Solid state characterization employing FT-IR and DSC studies
      indicated lack of significant interaction of drug with formulation excipients.
      Thus, the present studies ratify the suitability of chronomodulated bilayer
      tablets of AMT for effective management of bacterial infections owing to specific
      time-dependent drug release, higher gastric protection and enhanced antimicrobial
      activity.

PMID- 22998052
TI  - Raymond de Vieussens and his contribution to the study of white matter anatomy:
      historical vignette.
AB  - In recent years, there has been a renewed interest in the study of white matter
      anatomy, both with the use of postmortem dissections and diffusion tensor imaging
      tractography. One of the precursors in the study of white matter anatomy was
      Raymond de Vieussens (1641-1716), a French anatomist born in Le Vigan. He studied
      medicine at the University of Montpellier in southern France, one of the most
      ancient and lively schools of medicine in Europe. In 1684 Vieussens published his
      masterpiece, the Neurographia Universalis, which is still considered one of the
      most complete and accurate descriptions of the nervous system provided in the
      17th century. He described the white matter of the centrum ovale and was the
      first to demonstrate the continuity of the white matter fibers from the centrum
      ovale to the brainstem. He also described the dentate nuclei, the pyramids, and
      the olivary nuclei. According to the theory of Galen, Vieussens considered that
      the function of the white matter was to convey the "animal spirit" from the
      centrum ovale to the spinal cord. Although neglected, Vieussens' contribution to
      the study of white matter is relevant. His pioneering work showed that the white
      matter is not a homogeneous substance, but rather a complex structure rich in
      fibers that are interconnected with different parts of the brain. These initial
      results paved the way to advancements observed in later centuries that eventually
      led to modern hodology.

PMID- 22998053
TI  - Cavernous malformations.

PMID- 22998054
TI  - Magnetic resonance imaging and clips.

PMID- 22998055
TI  - Use of antithrombotic agents in patients with intracerebral cavernous
      malformations.
AB  - OBJECT: The goal of this study was to determine the risk of using antithrombotic
      agents in patients with established intracerebral cavernous malformations (ICMs).
      METHODS: From a previously described cohort of 292 patients with radiographically
      defined ICMs, 40 required an antithrombotic after the ICM was diagnosed. Patients
      underwent follow-up to determine the incidence of hemorrhage. RESULTS: The mean
      age of these 40 patients was 62.4 years; there were 21 male and 19 female
      patients. Five (12.5%) of the 40 patients initially presented with hemorrhage and
      4 (10%) had multiple ICMs. Of these patients, 32 were placed on an antiplatelet
      agent alone, 6 on an anticoagulant alone, and 2 were placed on both. In patients
      necessitating any antithrombotic agent, 1 patient developed a prospective
      hemorrhage over the 258 person-years of follow-up (prospective hemorrhage rate
      0.41% per person-year). CONCLUSIONS: Antithrombotics likely do not precipitate
      hemorrhage in patients with known ICMs. However, caution should be exercised in
      the use of antithrombotics in patients with ICMs at high risk for hemorrhage. The
      risks and benefits of antithrombotics in each situation should be carefully
      weighed against the natural history of ICM.

PMID- 22998056
TI  - Ultrasound-assisted convection-enhanced delivery to the brain in vivo with a
      novel transducer cannula assembly: laboratory investigation.
AB  - OBJECT: In convection-enhanced delivery (CED), drugs are infused locally into
      tissue through a cannula inserted into the brain parenchyma to enhance drug
      penetration over diffusion strategies. The purpose of this study was to
      demonstrate the feasibility of ultrasound-assisted CED (UCED) in the rodent brain
      in vivo using a novel, low-profile transducer cannula assembly (TCA) and
      portable, pocket-sized ultrasound system. METHODS: Forty Sprague-Dawley rats (350
      450 g) were divided into 2 equal groups (Groups 1 and 2). Each group was divided
      again into 4 subgroups (n = 5 in each). The caudate of each rodent brain was
      infused with 0.25 wt% Evans blue dye (EBD) in phosphate-buffered saline at 2
      different infusion rates of 0.25 MUl/minute (Group 1), and 0.5 MUl/minute (Group
      2). The infusion rates were increased slowly over 10 minutes from 0.05 to 0.25
      MUl/minute (Group 1) and from 0.1 to 0.5 MUl/minute (Group 2). The final flow
      rate was maintained for 20 minutes. Rodents in the 4 control subgroups were
      infused using the TCA without ultrasound and without and with microbubbles added
      to the infusate (CED and CED + MB, respectively). Rodents in the 4 UCED subgroups
      were infused without and with microbubbles added to the infusate (UCED and UCED +
      MB) using the TCA with continuous-wave 1.34-MHz low-intensity ultrasound at a
      total acoustic power of 0.11 +/- 0.005 W and peak spatial intensity at the
      cannula tip of 49.7 mW/cm(2). An additional 4 Sprague-Dawley rats (350-450 g)
      received UCED at 4 different and higher ultrasound intensities at the cannula tip
      ranging from 62.0 to 155.0 mW/cm(2) for 30 minutes. The 3D infusion distribution
      was reconstructed using MATLAB analysis. Tissue damage and morphological changes
      to the brain were assessed using H & E. RESULTS: The application of ultrasound
      during infusion (UCED and UCED + MB) improved the volumetric distribution of EBD
      in the brain by a factor of 2.24 to 3.25 when there were no microbubbles in the
      infusate and by a factor of 1.16 to 1.70 when microbubbles were added to the
      infusate (p < 0.001). On gross and histological examination, no damage to the
      brain tissue was found for any acoustic exposure applied to the brain.
      CONCLUSIONS: The TCA and ultrasound device show promise to improve the
      distribution of infused compounds during CED. The results suggest further studies
      are required to optimize infusion and acoustic parameters for small compounds and
      for larger molecular weight compounds that are representative of promising
      antitumor agents. In addition, safe levels of ultrasound exposure in chronic
      experiments must be determined for practical clinical evaluation of UCED.
      Extension of these experiments to larger animal models is warranted to
      demonstrate efficacy of this technique.

PMID- 22998057
TI  - Posttraumatic skull hemangioma: case report.
AB  - Intraosseous cavernous hemangiomas of the skull are rare lesions for which the
      origin is unclear. The authors present a case in which there was a radiologically
      documented history of trauma preceding the development of a hemangioma in the
      frontal bone.   In a review of the literature the authors found 83 cases of skull
      hemangiomas, and 43% of the lesions were located in the frontal bone. In 25% of
      these lesions, previous trauma was reported anamnestically. The present case and
      radiological findings related to it suggest a causal relationship between trauma
      and the development of intraosseous hemangioma.

PMID- 22998058
TI  - Subcortical surgical anatomy of the lateral frontal region: human white matter
      dissection and correlations with functional insights provided by intraoperative
      direct brain stimulation: laboratory investigation.
AB  - OBJECT: Recent neuroimaging and surgical results support the crucial role of
      white matter in mediating motor and higher-level processing within the frontal
      lobe, while suggesting the limited compensatory capacity after damage to
      subcortical structures. Consequently, an accurate knowledge of the
      anatomofunctional organization of the pathways running within this region is
      mandatory for planning safe and effective surgical approaches to different
      diseases. The aim of this dissection study was to improve the neurosurgeon's
      awareness of the subcortical anatomofunctional architecture for a lateral
      approach to the frontal region, to optimize both resection and postoperative
      outcome. METHODS: Ten human hemispheres (5 left, 5 right) were dissected
      according to the Klingler technique. Proceeding lateromedially, the main
      association and projection tracts as well as the deeper basal structures were
      identified. The authors describe the anatomy and the relationships among the
      exposed structures in both a systematic and topographical surgical perspective.
      Structural results were also correlated to the functional responses obtained
      during resections of infiltrative frontal tumors guided by direct cortico
      subcortical electrostimulation with patients in the awake condition. RESULTS: The
      eloquent boundaries crucial for a safe frontal lobectomy or an extensive
      lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and
      premotor fibers in the posterior and posteromedial part of the surgical field; 3)
      the inferior frontooccipital fascicle and the superior longitudinal fascicle
      posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the
      caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the
      depth. CONCLUSIONS: Optimization of results following brain surgery, especially
      within the frontal lobe, requires a perfect knowledge of functional anatomy, not
      only at the cortical level but also with regard to subcortical white matter
      connectivity.

PMID- 22998059
TI  - Volumetric analysis of subarachnoid hemorrhage: assessment of the reliability of
      two computerized methods and their comparison with other radiographic scales.
AB  - OBJECT: There were two main purposes to this study: first, to assess the
      feasibility and reliability of 2 quantitative methods to assess bleeding volume
      in patients who suffered spontaneous subarachnoid hemorrhage (SAH), and second,
      to compare these methods to other qualitative and semiquantitative scales in
      terms of reliability and accuracy in predicting delayed cerebral ischemia (DCI)
      and outcome. METHODS: A prospective series of 150 patients consecutively admitted
      to the Hospital 12 de Octubre over a 4-year period were included in the study.
      All of these patients had a diagnosis of SAH, and diagnostic CT was able to be
      performed in the first 24 hours after the onset of the symptoms. All CT scans
      were evaluated by 2 independent observers in a blinded fashion, using 2 different
      quantitative methods to estimate the aneurysmal bleeding volume: region of
      interest (ROI) volume and the Cavalieri method. The images were also graded using
      the Fisher scale, modified Fisher scale, Claasen scale, and the semiquantitative
      Hijdra scale. Weighted kappa coefficients were calculated for assessing the
      interobserver reliability of qualitative scales and the Hijdra scores. For
      assessing the intermethod and interrater reliability of volumetric measurements,
      intraclass correlation coefficients (ICCs) were used as well as the methodology
      proposed by Bland and Altman. Finally, weighted kappa coefficients were
      calculated for the different quartiles of the volumetric measurements to make
      comparison with qualitative scales easier. Patients surviving more than 48 hours
      were included in the analysis of DCI predisposing factors and analyzed using the
      chi-square or the Mann-Whitney U-tests. Logistic regression analysis was used for
      predicting DCI and outcome in the different quartiles of bleeding volume to
      obtain adjusted ORs. The diagnostic accuracy of each scale was obtained by
      calculating the area under the receiver operating characteristic curve (AUC).
      RESULTS: Qualitative scores showed a moderate interobserver reproducibility
      (weighted kappa indexes were always < 0.65), whereas the semiquantitative and
      quantitative scores had a very strong interobserver reproducibility. Reliability
      was very high for all quantitative measures as expressed by the ICCs for
      intermethod and interobserver agreement. Poor outcome and DCI occurred in 49% and
      31% of patients, respectively. Larger bleeding volumes were related to a poorer
      outcome and a higher risk of developing DCI, and the proportion of patients
      suffering DCI or a poor outcome increased with each quartile, maintaining this
      relationship after adjusting for the main clinical factors related to outcome.
      Quantitative analysis of total bleeding volume achieved the highest AUC, and had
      a greater discriminative ability than the qualitative scales for predicting the
      development of DCI and outcome. CONCLUSIONS: The use of quantitative measures may
      reduce interobserver variability in comparison with categorical scales. These
      measures are feasible using dedicated software and show a better prognostic
      capability in relation to outcome and DCI than conventional categorical scales.

PMID- 22998060
TI  - Effect of slosh mitigation on histologic markers of traumatic brain injury:
      laboratory investigation.
AB  - OBJECT: Helmets successfully prevent most cranial fractures and skull traumas,
      but traumatic brain injury (TBI) and concussions continue to occur with
      frightening frequency despite the widespread use of helmets on the athletic field
      and battlefield. Protection against such injury is needed. The object of this
      study was to determine if slosh mitigation reduces neural degeneration, gliosis,
      and neuroinflammation. METHODS: Two groups of 10 adult male Sprague-Dawley rats
      were subjected to impact-acceleration TBI. One group of animals was fitted with a
      collar inducing internal jugular vein (IJV) compression prior to injury, whereas
      the second group received no such collar prior to injury. All rats were killed 7
      days postinjury, and the brains were fixed and embedded in paraffin. Tissue
      sections were processed and stained for markers of neural degeneration (Fluoro
      Jade B), gliosis (glial fibrillary acidic protein), and neuroinflammation
      (ionized calcium binding adapter molecule 1). RESULTS: Compared with the
      controls, animals that had undergone IJV compression had a 48.7%-59.1% reduction
      in degenerative neurons, a 36.8%-45.7% decrease in reactive astrocytes, and a
      44.1%-65.3% reduction in microglial activation. CONCLUSIONS: The authors
      concluded that IJV compression, a form of slosh mitigation, markedly reduces
      markers of neurological injury in a common model of TBI. Based on findings in
      this and other studies, slosh mitigation may have potential for preventing TBI in
      the clinical population.

PMID- 22998061
TI  - Shunting with gravitational valves--can adjustments end the era of revisions for
      overdrainage-related events?: clinical article.
AB  - OBJECT: Overdrainage of CSF remains an unsolved problem in shunt therapy. The aim
      of the present study was to evaluate treatment options on overdrainage-related
      events enabled by the new generation of adjustable gravity-assisted valves.
      METHODS: The authors retrospectively studied the clinical course of 250
      consecutive adult patients with various etiologies of hydrocephalus after shunt
      insertion for different signs and symptoms of overdrainage. Primary and secondary
      overdrainage were differentiated. The authors correlated the incidence of
      overdrainage with etiology of hydrocephalus, opening valve pressure, and patient
      parameters such as weight and size. Depending on the severity of overdrainage,
      they elevated the opening pressure, and follow-up was performed until
      overdrainage was resolved. RESULTS: The authors found 39 cases (15.6%) involving
      overdrainage-related problems--23 primary and 16 secondary overdrainage. The
      median follow-up period in these 39 patients was 2.1 years. There was no
      correlation between the incidence of overdrainage and any of the following
      factors: sex, age, size, or weight of the patients. There was also no statistical
      significance among the different etiologies of hydrocephalus, with the exception
      of congenital hydrocephalus. All of the "complications" could be resolved by
      readjusting the opening pressure of the valve in one or multiple steps, avoiding
      further operations. CONCLUSIONS: Modern adjustable and gravity-assisted valves
      enable surgeons to set the opening pressure relatively low to avoid underdrainage
      without significantly raising the incidence of overdrainage and to treat
      overdrainage-related clinical and radiological complications without surgical
      intervention.

PMID- 22998062
TI  - Editorial: Convection-enhanced delivery.

PMID- 22998063
TI  - Comparison of spray congealing and melt emulsification methods for the
      incorporation of the water-soluble salbutamol sulphate in lipid microparticles.
AB  - CONTEXT: Salbutamol sulphate is widely used as bronchodilator for the treatment
      of asthma. Its use is limited by the relatively short duration of action and
      hence sustained delivery of salbutamol sulphate offers potential benefits to
      patients. OBJECTIVE: This study explores the preparation of lipid microparticles
      (LMs) as biocompatible carrier for the prolonged release of salbutamol sulphate.
      MATERIALS AND METHODS: The LMs were produced using different lipidic materials
      and surfactants, by classical melt emulsification-based methods (oil-in-water and
      water-in-oil-in-water emulsions) and the spray congealing technique. RESULTS: For
      the LMs obtained by melt emulsification a lack of release modulation was
      observed. On the other hand, the sustained release of salbutamol sulphate was
      achieved with glyceryl behenate microparticles prepared by spray congealing.
      These LMs were characterized by scanning electron microscopy, X-ray
      diffractometry and differential scanning calorimetry. The drug loading was 4.72%
      (w/w). The particle size distribution measured by laser diffraction and
      electrical zone sensing was represented by a volume median diameter (Dv(50)) of
      51.7-71.4 um. Increasing the atomization air pressure from 4 to 8 bar produced a
      decrease of the Dv(50) to 12.7-17.5 um. CONCLUSIONS: Incorporation of the
      hydrophilic salbutamol sulphate into LMs with sustained release characteristics
      was achieved by spray congealing.

PMID- 22998064
TI  - Galectin 3 complements BNP in risk stratification in acute heart failure.
AB  - BACKGROUND: Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart
      failure. METHODS: Patients diagnosed with and treated for Acute Heart Failure
      Syndromes were prospectively enrolled in the Decision Making in Acute
      Decompensated Heart Failure multicenter trial. RESULTS: Patients with a higher G3
      had a history of renal disease, a lower heart rate and acute kidney injury. They
      also tended to have a history of HF and 30-day adverse events compared with B
      type natriuretic peptide. CONCLUSION: In Acute Heart Failure Syndromes, G3 levels
      do not provide prognostic value, but when used complementary to B-type
      natriuretic peptide, G3 is associated with renal dysfunction and may predict 30
      day events.

PMID- 22998065
TI  - Oxidative stress as a potential biomarker for determining disease activity in
      patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis is an inflammatory, autoimmune disease where oxidative
      stress has been proposed to contribute to the joint tissue damage. To establish
      whether measurement of the redox status in blood mirrors the oxidant status at
      sites of inflammation in patients with rheumatoid arthritis, we concomitantly
      examined their oxidant status by spectrophotometry and/or flow cytometry. The
      basal levels of total reactive oxygen species (ROS), superoxide and hydroxyl
      radicals were significantly raised in neutrophils sourced from peripheral blood
      and synovial infiltrate, as also showed a strong positive correlation; however,
      there was no major increase in the reactive nitrogen species RNS generated in
      monocytes from both sources. Furthermore, raised levels of superoxide in
      neutrophils of synovial infiltrate showed a positive correlation with NADPH
      oxidase activity in synovial fluid. Additionally, as ROS generated in both
      peripheral blood and synovial infiltrate correlated positively with both DAS 28
      and CRP/anti-CCP levels, its measurement can serve as an indirect measure of the
      degree of inflammation in patients with RA.

PMID- 22998066
TI  - The effects of gastric bypass surgery on drug absorption and pharmacokinetics.
AB  - INTRODUCTION: Being overweight is widespread in most societies and represents a
      major health threat. Gastric bypass surgery offers a highly effective mode of
      treatment for the morbidly obese patients. The procedures cause an alteration in
      normal gastrointestinal anatomy and physiology, with consequences not only on
      nutrient absorption, but also possibly on orally administered drugs. Bypass of
      the acidic environment of the stomach, partial impairment of bile salts-drug
      interactions and reduced absorptive surface, all create the potential for reduced
      absorption of drugs. AREAS COVERED: This article provides an overview of the
      effects of obesity and the most prevalent type of gastric bypass (Roux-en-Y) on
      pharmacokinetics. Articles for review were searched using Pubmed. EXPERT OPINION:
      The absorption of those drugs with known bioavailability issues generally seem to
      be most affected by bypass surgery. It is important to consider the effect of
      obesity on pharmacokinetics independent of the bypass procedure, because it leads
      to a dramatic drop in body mass over a relatively short period of time. This may
      be associated with reversals in the influence of obesity on drug disposition to
      characteristics more in line with leaner patients. Drugs will differ in their
      pharmacokinetic response to surgery, limiting any general conclusions regarding
      the impact of the surgery on drug disposition.

PMID- 22998067
TI  - Reported medication errors after introducing an electronic medication management
      system.
AB  - AIMS AND OBJECTIVES: To explore the effects of introducing an electronic
      medication management system on reported medication errors. BACKGROUND:
      Computerised medication management systems have been found to improve medication
      safety; however, introducing medication management system into healthcare
      environments can create unanticipated or new problems and opportunities for
      medication error. DESIGN: Descriptive analysis of medication error reports.
      METHODS: This was a retrospective analysis of 359 incident reports drawn from the
      period of 1 May 2005-30 April 2006 across two hospital sites of a single not-for
      profit private health service located in metropolitan Melbourne. Site A used a
      conventional pen and paper system for medication management, and Site B had
      introduced a computerised medication management system. RESULTS: Most medication
      errors occurred at the nurse administration (71.5%) and prescribing (16.4%)
      stages of delivery. The most common medication error type reported at Site A was
      omission (33%), and at Site B was wrong documentation (24.2%). A higher
      proportion of errors at the prescribing phase, and less nurse administration
      errors, were detected at Site B where the medication management system was in
      use. The incidence of other, less frequent errors was similar across the two
      hospital sites. CONCLUSIONS: This examination of medication error reports
      suggests there are differences in the types of medication errors that are
      reported in association with the introduction of electronic medication management
      system compared to pen and paper system systems. The findings provide a new
      insight into the effects of introducing an electronic medication management
      system on the types of medication errors reported. RELEVANCE TO CLINICAL
      PRACTICE: The findings provide a new insight into the types of medication errors
      that are reported during implementation of an electronic medication management
      system. Extra support for physicians prescribing practices should be considered.

PMID- 22998069
TI  - Temperature cycling improves in vivo recovery of cold-stored human platelets in a
      mouse model of transfusion.
AB  - BACKGROUND: Platelet (PLT) storage at room temperature (RT) is limited to 5 days
      to prevent growth of bacteria, if present, to high levels. Storage in cold
      temperatures would reduce bacterial proliferation, but cold-exposed PLTs are
      rapidly cleared from circulation by the hepatic Ashwell-Morell (AM) receptor,
      which recognizes PLT surface carbohydrates terminated by beta-galactose. We
      cycled storage temperature between 4 and 37 degrees C to preserve PLT function
      and reduce bacterial growth. STUDY DESIGN AND METHODS: Temperature-cycled (TC)
      human PLTs were stored at 4 degrees C for 12 hours and then incubated at 37
      degrees C for 30 minutes before returning back to cold storage. PLTs stored at RT
      or at 4 degrees C (COLD) or TC for 2, 5, and 7 days were infused into SCID mice
      and the in vivo recovery was determined at 5, 20, and 60 minutes after
      transfusion. RESULTS: PLTs stored for 2 days in COLD had significantly lower in
      vivo recoveries than RT PLTs. TC PLTs had improved recoveries over COLD and
      comparable to RT PLTs. After 5- and 7-day storage, TC PLTs had better recoveries
      than RT and COLD PLTs. PLT surface beta-galactose was increased significantly for
      both COLD and TC PLTs compared to RT. Blocking of the AM receptor by asialofetuin
      increased COLD but not TC PLT recovery. CONCLUSION: TC cold storage may be an
      effective method to store PLTs without loss of in vivo recovery. The increased
      beta-galactose exposure in TC PLTs suggests that mechanisms in addition to AM
      receptors may mediate clearance of cold-stored PLTs.

PMID- 22998068
TI  - Decreasing mortality and changing patterns of causes of death in the Swiss HIV
      Cohort Study.
AB  - BACKGROUND: Mortality among HIV-infected persons is decreasing, and causes of
      death are changing. Classification of deaths is hampered because of low autopsy
      rates, frequent deaths outside of hospitals, and shortcomings of International
      Statistical Classification of Diseases and Related Health Problems (ICD-10)
      coding. METHODS: We studied mortality among Swiss HIV Cohort Study (SHCS)
      participants (1988-2010) and causes of death using the Coding Causes of Death in
      HIV (CoDe) protocol (2005-2009). Furthermore, we linked the SHCS data to the
      Swiss National Cohort (SNC) cause of death registry. RESULTS: AIDS-related
      mortality peaked in 1992 [11.0/100 person-years (PY)] and decreased to 0.144/100
      PY (2006); non-AIDS-related mortality ranged between 1.74 (1993) and 0.776/100 PY
      (2006); mortality of unknown cause ranged between 2.33 and 0.206/100 PY. From
      2005 to 2009, 459 of 9053 participants (5.1%) died. Underlying causes of deaths
      were: non-AIDS malignancies [total, 85 (19%) of 446 deceased persons with known
      hepatitis C virus (HCV) status; HCV-negative persons, 59 (24%); HCV-coinfected
      persons, 26 (13%)]; AIDS [73 (16%); 50 (21%); 23 (11%)]; liver failure [67 (15%);
      12 (5%); 55 (27%)]; non-AIDS infections [42 (9%); 13 (5%); 29 (14%)]; substance
      use [31 (7%); 9 (4%); 22 (11%)]; suicide [28 (6%); 17 (7%), 11 (6%)]; myocardial
      infarction [28 (6%); 24 (10%), 4 (2%)]. Characteristics of deceased persons
      differed in 2005 vs. 2009: median age (45 vs. 49 years, respectively); median CD4
      count (257 vs. 321 cells/MUL, respectively); the percentage of individuals who
      were antiretroviral therapy-naive (13 vs. 5%, respectively); the percentage of
      deaths that were AIDS-related (23 vs. 9%, respectively); and the percentage of
      deaths from non-AIDS-related malignancies (13 vs. 24%, respectively). Concordance
      in the classification of deaths was 72% between CoDe and ICD-10 coding in the
      SHCS; and 60% between the SHCS and the SNC registry. CONCLUSIONS: Mortality in
      HIV-positive persons decreased to 1.33/100 PY in 2010. Hepatitis B or C virus
      coinfections increased the risk of death. Between 2005 and 2009, 84% of deaths
      were non-AIDS-related. Causes of deaths varied according to data source and
      coding system.

PMID- 22998070
TI  - When is azoospermic infertility treatable without intracytoplasmic sperm
      injection?
AB  - Infertility with azoospermia requires a diligent search for reversible factors
      and treatment to restore natural fertility, even though most cases are due to
      untreatable primary spermatogenic failure and are destined to require
      consideration of assisted reproductive treatment (ART) options. Complete clinical
      and diagnostic evaluation is essential for avoiding both unnecessary ART and
      overlooking important co-morbidities. Gonadotrophin deficiency is the most
      treatable cause, resulting from drug effects or congenital or acquired disease,
      and medical therapy is highly efficacious. A range of uncommon
      endocrinocrinopathies may also result in reversible azoospermia. Finally,
      obstructive azoospermia may be surgically remediable in selected cases.

PMID- 22998072
TI  - Characteristic size for onset of coffee-ring effect in evaporating lysozyme-water
      solution droplets.
AB  - Liquid droplets containing suspended particles deposited on a solid surface often
      form a ring-like structure due to the redistribution of solute during
      evaporation, a phenomenon known as the "coffee ring effect". The complex patterns
      left on the substrate after evaporation are characteristic of the nature of the
      solute and the particle transport mechanisms. In this study, the morphological
      evolution and conditions for coffee ring formation for simplified model
      biological solutions of DI water and lysozyme are examined by AFM and optical
      microscopy. Lysozyme is a globular protein found in high concentration, for
      example, in human tears and saliva. The drop diameters studied are very small,
      ranging from 1 to 50 MUm. In this size range, protein motion and the resulting
      dried residue morphology are highly influenced by the decreased evaporation time
      of the drop. In this work, we consider the effect of droplet size and
      concentration on the morphology of the deposited drop as well as the minimal
      conditions for coffee ring formation in this system. Two distinct deposit types
      are observed: a simple cap-shaped deposit for drops with small diameters and a
      ring-like deposit at larger diameters. Ring formation occurs at a critical
      diameter, which depends systematically on initial lysozyme concentration.

PMID- 22998073
TI  - Solid-state compatibility screening of excipients suitable for development of
      indapamide sustained release solid-dosage formulation.
AB  - Differential scanning calorimetry and Fourier transform infrared spectroscopy
      were applied as screening analytical methods to assess the solid-state
      compatibility of indapamide (4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3
      sulfamoyl-benzamide) with several polymers aimed for development of 24 h
      sustained release solid-dosage formulation. After the initial research phase
      which was directed towards selection of suitable polymer matrices, based on their
      solid-state compatibility with the studied pharmaceutical active ingredient, the
      second phase of evaluation was intended for compatibility selection of other
      excipients required to complete a sustained release formulation. The
      preformulation studies have shown that polyvinylpyrrolydone/polyvinyl acetate
      might be considered incompatible with indapamide, and the implementation of this
      polymer career should be avoided in the case of the entitled development. The
      experimental data additionally have revealed that sorbitol is incompatible with
      indapamide. The obtained results afforded deeper insight in to the solid-state
      stability of the studied binary systems and pointed out directions for further
      development of indapamide sustained release solid-dosage formulation.

PMID- 22998074
TI  - Comparative performance of GlideScope((r))  videolaryngoscope and FastrachTM
      intubation laryngeal mask airway in the morbidly obese patients.

PMID- 22998075
TI  - Using plasticizers to control the hydrocarbon selectivity of a poly(methyl
      methacrylate)-coated quartz crystal microbalance sensor.
AB  - Chemical sensors based on a polymer coated quartz crystal microbalance (QCM)
      generally present poor molecular selectivity for compounds that contain similar
      functional groups and possess the same chemical properties. This paper shows for
      the first time that the selectivity and sensitivity of a poly(methyl
      methacrylate) (PMMA) based QCM sensor can be significantly enhanced for aromatic
      hydrocarbons by incorporating a plasticizer into the polymer film. The sensor was
      fabricated by spin coating PMMA onto a quartz crystal, and the influence of
      plasticizer type and amount on the response was evaluated. It was shown that the
      hydrocarbon sensitivity of plasticizer-free PMMA is negligible, while the
      sensitivity of plasticized PMMA was similar to or in some cases greater relative
      to highly responsive rubbery polymers such as polyisobutylene (PIB). Detection
      limits of 4.0, 1.5, 0.4, 0.6, and 0.1 ppm were obtained on a PMMA film containing
      25% w/w di(2-ethylhexyl) phthalate for benzene, toluene, ethylbenzene, p-xylene,
      and naphthalene, respectively. We found that at low plasticizer levels (~10% w/w)
      the PMMA film was more sensitive toward ethylbenzene and p-xylene over
      naphthalene when compared to a PIB film under similar measurement conditions.
      Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR)
      measurements were performed to understand the sensing mechanism, and these
      studies confirmed a higher hydrocarbon uptake by PMMA in the presence of
      plasticizer. Positron annihilation lifetime spectroscopy (PALS) studies detected
      variations in the free volume properties of the polymer films as a function of
      plasticizer content. The accessible free volume as measured by PALS was
      significantly less in the PMMA films compared to the PIB, and this result
      correlates favorably with differences in the QCM response pattern. The QCM
      results have been rationalized in terms of free volume theory which is
      responsible for the higher hydrocarbon diffusion/sorption with increased
      plasticizer content.

PMID- 22998076
TI  - Phenylephrine 5% added to tropicamide 0.5% eye drops does not influence retinal
      oxygen saturation values or retinal vessel diameter in glaucoma patients.
AB  - PURPOSE: To test whether adding topical phenylephrine 5% to tropicamide 0.5% eye
      drops in the protocol for pupil dilation affects the retinal vessel oximeter
      measurements in patients with glaucoma. To test whether phenylephrine 5% has an
      influence as a vasoconstrictor on the retinal vessel width and can improve the
      proportion of high-quality retinal images in patients with glaucoma. METHODS:
      Retinal images of 66 patients with chronic open-angle glaucoma were obtained
      before and after the administration of phenylephrine 5% eye drops to patients
      already dilated with tropicamide 0.5% with the Oxymap Retinal Oximeter (Oxymap
      ehf, Reykjavik, Iceland). Specialized software, Oxymap Analyzer, analysed the
      images and measured the oxygen saturation and vessel diameter. Oxygen saturation
      was measured in first- and second-degree vessels. A Mann-Whitney U-test was used
      to compare both groups. Quality of the images was assessed, and a Fisher's exact
      test was used to compare the proportion of high- and poor-quality images.
      RESULTS: There was no significant difference in arterial and venous oxygen
      saturation in patients with glaucoma whether dilated by tropicamide alone or a
      combination of tropicamide and phenylephrine (97 +/- 6% versus 96 +/- 5%, p =
      0.88 for arterial saturation and 66 +/- 6% versus 67 +/- 6%, p = 0.78 for venous
      saturation, n = 27). There was no significant difference in vessel diameter
      between both conditions for the different vessels (p = 0.61 for arterial
      saturation and p = 0.51 for venous saturation, n = 27). The proportion of high
      quality images was significantly higher after the combination regimen compared
      with tropicamide only (p = 0.0001). CONCLUSION: The addition of topical
      phenylephrine 5% after tropicamide 0.5% improved the proportion of high-quality
      retinal oximetry images without influencing the retinal oxygen saturation values
      or the retinal vessel diameter in patients with glaucoma.

PMID- 22998077
TI  - Nanofluidic ion transport through reconstructed layered materials.
AB  - Electrolytes confined in nanochannels with characteristic dimensions comparable
      to the Debye length show transport behaviors deviating from their bulk
      counterparts. Fabrication of nanofluidic devices typically relies on expensive
      lithography techniques or the use of sacrificial templates with sophisticated
      growth and processing steps. Here we demonstrate an alternative approach where
      unprecedentedly massive arrays of nanochannels are readily formed by restacking
      exfoliated sheets of layered materials, such as graphene oxide (GO). Nanochannels
      between GO sheets are successfully constructed as manifested by surface-charge
      governed ion transport for electrolyte concentrations up to 50 mM. Nanofluidic
      devices based on reconstructed layer materials have distinct advantages such as
      low cost, facile fabrication, ease of scaling up to support high ionic currents,
      and flexibility. Given the rich chemical, physical, and mechanical properties of
      layered materials, they should offer many exciting new opportunities for studying
      and even manufacturing nanofluidic devices.

PMID- 22998078
TI  - Fatal BK virus pneumonia following stem cell transplantation.
AB  - We report the case of a 39-year-old male patient who died of severe BK virus
      (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for
      acute lymphoblastic leukemia. After suffering from BKV-associated late-onset
      hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of
      rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions
      were seen in his lungs and bladder. An immunohistochemical examination of his
      lungs was positive for simian virus 40. Based on these pathological results and
      the high sustained BKV viral load in his blood, we reached a diagnosis of BKV
      pneumonia. Viral infection can occasionally become life threatening among HSCT
      recipients. It is widely known that BKV can cause late-onset HC, but BKV
      associated pneumonia is rare. Because of its rapid progression and poor
      prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A
      treatment strategy for BKV pneumonia also needs to be formulated. Similar to
      other viral pathogens, BKV can cause pneumonia and the clinician should therefore
      be aware of it in immunocompromised patients.

PMID- 22998079
TI  - Impact of SOD in eNOS uncoupling: a two-edged sword between hydrogen peroxide and
      peroxynitrite.
AB  - In endothelial cell dysfunction, the uncoupling of eNOS results in higher
      superoxide (O(2)(*-)) and lower NO production and a reduction in NO availability.
      Superoxide reacts with NO to form a potent oxidizing agent peroxynitrite (ONOO(
      )) resulting in nitrosative and nitroxidative stresses and dismutates to form
      hydrogen peroxide. Studies have shown superoxide dismutase (SOD) plays an
      important role in reduction of O(2)(*-) and ONOO(-) during eNOS uncoupling.
      However, the administration or over-expression of SOD was ineffective or
      displayed deleterious effects in some cases. An understanding of interactions of
      the two enzyme systems eNOS and SOD is important in determining endothelial cell
      function. We analyzed complex biochemical interactions involving eNOS and SOD in
      eNOS uncoupling. A computational model of biochemical pathway of the eNOS-related
      NO and O(2)(*-) production and downstream reactions involving NO, O(2)(*-), ONOO(
      ), H(2)O(2) and SOD was developed. The effects of SOD concentration on the
      concentration profiles of NO, O(2)(*-), ONOO(-) and H(2)O(2) in eNOS
      coupling/uncoupling were investigated. The results include (i) SOD moderately
      improves NO production and concentration during eNOS uncoupling, (ii) O(2)(*-)
      production rate is independent of SOD concentration, (iii) Increase in SOD
      concentration from 0.1 to 100 MUM reduces O(2)(*-) concentration by 90% at all
      [BH(4)]/[TBP] ratios, (iv) SOD reduces ONOO(-) concentration and increases
      H(2)O(2) concentration during eNOS uncoupling, (v) Catalase can reduce H(2)O(2)
      concentration and (vi) Dismutation rate by SOD is the most sensitive parameter
      during eNOS uncoupling. Thus, SOD plays a dual role in eNOS uncoupling as an
      attenuator of nitrosative/nitroxidative stress and an augmenter of oxidative
      stress.

PMID- 22998080
TI  - Pd(0)-catalyzed decarboxylative coupling and tandem C-H arylation/decarboxylation
      for the synthesis of heteroaromatic biaryls.
AB  - An effective Pd(0) carbene complex was successfully employed in the
      decarboxylative coupling of the heteroaromatic carboxylic acids (imidazo[1,2
      a]pyridine and isoxazole) with aryl halides. For carboxyindoles, either
      decarboxylative coupling or tandem C-H arylation and decarboxylation occurred,
      leading to the formation of C2-monoarylated indoles.

PMID- 22998081
TI  - Prevalence of abnormal urinary albumin excretion in a population-based study in
      Spain: results from the HERMEX Study.
AB  - BACKGROUND: HERMEX is a population-based study which try to evaluate the relative
      weight of cardiovascular risk factors in the population of Extremadura. This
      report provides the data obtained about microalbuminuria in a large Spanish
      population. DESIGN AND METHODS: Observational, cross-sectional, population-based
      study. A total of 3402 subjects were randomly selected from the Health Care
      System of Extremadura. The final sample included 2813 subjects (mean age 51.2
      years, 53.5% female). Urinary albumin excretion rate (UAER) in first morning
      urine sample was analysed. Microalbuminuria was diagnosed when UAER was >= 22 in
      men or >= 31 mg/g in women. RESULTS: Prevalence of abnormal UAER in general
      population was 5.5% (microalbuminuria: 4.7%; proteinuria 0.8%). Microalbuminuria
      grew slightly in patients between 65 and 74 years and showed a dramatic increase
      in subject older than 75 years (P < 0.001). Men showed a high prevalence of
      microalbuminuria (5.8% vs. women 3.6%; P = 0.006 chi-squared test). Increased
      UAER was more common in obese subjects (6.7% vs. 2.3%, P < 0.001), hypertensive
      patients (8.3% vs. 2.3%, P < 0.001) and diabetic ones (10.9% vs. 3.7%, P <
      0.001). The multivariate analysis showed a positive correlation of abnormal UAER
      with body mass index (BMI), systolic blood pressure, plasma creatinine and
      triglyceride levels. CONCLUSIONS: A low frequency of abnormal UAER was detected
      in a randomly selected sample of Spanish general population. This finding agreed
      with the low rates of cardiovascular mortality and morbidity observed in Spain in
      spite of a high prevalence of classic cardiovascular risk factors.

PMID- 22998083
TI  - Genome-wide association study of resistant starch (RS) phenotypes in a barley
      variety collection.
AB  - Barley is primarily grown for feed and malt, but in some regions of the world it
      is also considered to be a staple food. Some barley types such as high-amylose
      barley have also gained importance as health-promoting foods. Starch that is not
      readily digested in the upper mammalian gastrointestinal system, or resistant
      starch (RS), is considered to be valuable because it prevents some diet-related
      diseases such as colon cancer. RS was quantified in a diverse collection of 209
      spring barley varieties released in Europe during the past 100 years. The RS
      content varied from <1% to >15% in the collection, with 13 varieties having high
      RS content (>11%) and 15 varieties below 1%. Combined with genome-wide
      association scanning (GWAS), SNP markers and candidate genes controlling the RS
      content in grains were identified. This identified 40 SNP markers with a LOD
      score above 2, located on chromosomes 2H, 3H, 5H, and 6H, respectively. Among
      these SNPs, 10 genes with a known role in starch biosynthesis were associated on
      the basis of synteny conservation to the rice genome. The beta-glucan content was
      quantified in 61 varieties selected to represent extreme as well as medium RS
      values. The beta-glucan amount in the 15 varieties with RS <1% ranged from 1.7 to
      3.2%, ranged from 1.76 to 2.54% in the 13 varieties with RS >11%, and ranged from
      1.95 to 2.82% for those with 1%< RS < 11%. No statistically significant
      correlation between RS content and beta-glucan content was found. This
      association analysis of commercial varieties revealed a large variation in RS
      content and identified a number of SNP markers that can be explored for selection
      and further dissection of the pathway and control of RS phenotype.

PMID- 22998082
TI  - MicroRNA expression profile of the hippocampus in a rat model of temporal lobe
      epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell
      apoptosis post-status epilepticus.
AB  - BACKGROUND: The expression pattern and function of miRNAs in the rat model of
      temporal lobe epilepsy have not been well defined. Profiling miRNA expression in
      the rat model of temporal lobe epilepsy and investigating the function of
      specific miRNAs in epilepsy offers the prospect of a deeper understanding of the
      mechanisms of epilepsy. METHODS: The lithium-pilocarpine-induced status
      epilepticus model and the temporal lobe epilepsy model were established in
      Sprague-Dawley rats. Samples were analysed to detect deregulated miRNAs in the
      hippocampal temporal lobe, and several of these deregulated miRNAs were confirmed
      by qPCR. The expression of the pro-apoptotic miR-34a was detected at 1 day, 7
      days and 2 weeks post-status epilepticus and at 2 months after temporal lobe
      epilepsy. The antagomir of miR-34a was then utilised. The expression of miR-34a
      after targeting and the expression change of activated caspase-3 protein were
      examined. The effects of altering the expression of miR-34a and activated caspase
      3 protein on neuronal survival and neuronal death or apoptosis post-status
      epilepticus were assessed. RESULTS: The miRNA microarray detected 9 up-regulated
      miRNAs (miR-146a, -211, -203, -210, -152, -31, -23a, -34a, -27a) and 15 down
      regulated miRNAs (miR-138*, -301a, -136, -153, -19a, -135b, -325-5p, -380, -190, 
      542-3p, -33, -144, -542-5p, -543, -296*). Some of the deregulated miRNAs (miR
      146a, miR-210, miR-27a, miR-135b and miR-33) were confirmed using qPCR.
      Furthermore, an increase in expression of the pro-apoptotic miR-34a was
      demonstrated in the post-status epilepticus rat hippocampus. miR-34a was
      significantly up-regulated at 1 day, 7 days and 2 weeks post-status epilepticus
      and at 2 months after temporal lobe epilepsy. Experiments with the miR-34a
      antagomir revealed that targeting miR-34a led to an inhibition of activated
      caspase-3 protein expression, which may contribute to increased neuronal survival
      and reduced neuronal death or apoptosis. CONCLUSIONS: Our study showed the
      expression profile of miRNAs in the hippocampus in a rat model of temporal lobe
      epilepsy and an increase in the expression of the pro-apoptotic miR-34a in post
      status epilepticus rats. The results show that miR-34a is up-regulated during
      seizure-induced neuronal death or apoptosis, and targeting miR-34a is
      neuroprotective and is associated with an inhibition of an increase in activated
      caspase-3 protein.

PMID- 22998084
TI  - Shiitake dermatitis: a distinctive clinical entity.

PMID- 22998085
TI  - Validation of spirometer calibration syringes.
AB  - The volume calibration syringe is probably the single most important instrument
      in pulmonary function laboratories, yet no validation results have been
      published. In this study a sample of volume calibration syringes was validated.
      We weighed a 1-L and two 3-L calibration syringes before and after emptying them
      of water and determined the corresponding volume of gas by using a modified
      rolling seal spirometer. In this way we established an unbroken calibration chain
      between a certified weight of water and the corresponding volume of gas. The
      volume of a spirometer calibration syringe could be verified with an accuracy of
      +/- 15 ml. The modified rolling seal spirometer had an accuracy of +/- 11 ml at a
      volume of 1 L and +/- 13 ml at a volume of 3 L. A sample of spirometer
      calibration syringes was validated and all syringes except for two small 1-liter
      syringes all had volumes within the label claimed volume +/- 0.5%. Spirometer
      calibration syringes have a stable stroke volume even after many years of use and
      storage but have to be calibrated yearly to comply with international standard.

PMID- 22998086
TI  - LC-MS-based analytical strategies for targeted profiling of
      metabolites/biomarkers in complex systems.

PMID- 22998087
TI  - Drugs and the upper and lower gastrointestinal tract: from inflammation to
      malignancy.

PMID- 22998088
TI  - Lipids in Australian children: cause for concern? 2005-2007 Busselton Health
      Study.
AB  - AIM: To report the current lipid status of Australian school children from a
      population-based sample and compare this to international and Australian data.
      METHODS: A cross section of school children aged 6 to 16.9 years in Busselton,
      Western Australia (WA) between 2005 and 2007 had fasting lipids tested. The first
      analysis compares the Busselton sample to data recommended by the American
      Academy of Paediatrics (AAP) 2008. The second analysis compares the Busselton
      sample to data from the Schools Physical Activity and Nutrition Survey (SPANS)
      study, New South Wales (NSW), Australia, 2004 and the 1985 Australian Health and
      Fitness Survey (AHFS). The third analysis applies laboratory-reported cut-points
      in WA to report percentages over 'healthy desirable norms'. RESULTS: Analysis 1:
      higher levels of total cholesterol and triglycerides in Busselton children
      compared to AAP data source. Boys had higher low-density lipoprotein (LDL)
      levels. Analysis 2: comparable rates of dyslipidaemia to SPANS 2004 but lower
      rates compared to the AHFS, 1985. Analysis 3: total and LDL-cholesterol above
      recommended range in 32.7% and 19.4% of boys and 38.2% and 24.6% of girls.
      CONCLUSION: In a large population-based sample of Australian school children, we
      found a higher frequency of abnormal lipid profiles when compared to American
      data. In addition, many children have levels outside reported healthy norms for
      Australian children. Research tracking lipid profiles of Australian children into
      adulthood is needed to understand the association of these levels with future
      cardiovascular risk.

PMID- 22998089
TI  - Challenges and strategies in transcriptome assembly and differential gene
      expression quantification. A comprehensive in silico assessment of RNA-seq
      experiments.
AB  - Transcriptome Shotgun Sequencing (RNA-seq) has been readily embraced by
      geneticists and molecular ecologists alike. As with all high-throughput
      technologies, it is critical to understand which analytic strategies are best
      suited and which parameters may bias the interpretation of the data. Here we use
      a comprehensive simulation approach to explore how various features of the
      transcriptome (complexity, degree of polymorphism pi, alternative splicing),
      technological processing (sequencing error epsilon, library normalization) and
      bioinformatic workflow (de novo vs. mapping assembly, reference genome quality)
      impact transcriptome quality and inference of differential gene expression (DE).
      We find that transcriptome assembly and gene expression profiling (EdgeR vs.
      BaySeq software) works well even in the absence of a reference genome and is
      robust across a broad range of parameters. We advise against library
      normalization and in most situations advocate mapping assemblies to an annotated
      genome of a divergent sister clade, which generally outperformed de novo assembly
      (Trans-Abyss, Trinity, Soapdenovo-Trans). Transcriptome complexity (size,
      paralogs, alternative splicing isoforms) negatively affected the assembly and DE
      profiling, whereas the effects of sequencing error and polymorphism were almost
      negligible. Finally, we highlight the challenge of gene name assignment for de
      novo assemblies, the importance of mapping strategies and raise awareness of
      challenges associated with the quality of reference genomes. Overall, our results
      have significant practical and methodological implications and can provide
      guidance in the design and analysis of RNA-seq experiments, particularly for
      organisms where genomic background information is lacking.

PMID- 22998090
TI  - Prospective evaluation of NT-proBNP assay to detect occult dilated cardiomyopathy
      and predict survival in Doberman Pinschers.
AB  - BACKGROUND: Occult (asymptomatic) dilated cardiomyopathy (ODCM) is highly
      prevalent in Doberman Pinschers. HYPOTHESIS/OBJECTIVES: Assess ability of NT
      proBNP assay to detect ODCM and predict death. ANIMALS: 155 asymptomatic
      Dobermans presenting for ODCM screening. METHODS: Echocardiography, 24-hour
      Holter, and NT-proBNP assay were performed prospectively. Diagnosis was based on
      increased left ventricular end-systolic dimension, >50 ventricular premature
      complexes (VPCs), or both on Holter. Utility was evaluated using receiver
      operating characteristic curves. Effect of age, weight, sex, disease status,
      VPCs, and NT-proBNP on survival was analyzed using Kaplan-Meier and Cox
      proportional hazard analysis. RESULTS: Seventy-three (47.1%) Dobermans were
      diagnosed with ODCM, including 31, 17, and 25 that met Holter, echocardiographic,
      or both criteria, respectively. Sensitivity of NT-proBNP > 457 pmol/L to detect
      these groups was 45.2, 76.5, and 96.0%, respectively. Combination of NT-proBNP
      and Holter to detect ODCM yielded sensitivity of 94.5%, specificity of 87.8%, and
      accuracy of 91.0%. Follow-up data were available for 78 Dobermans. The median
      survival time of Dobermans with > 50 VPCs (469 days), NT-proBNP > 900 pmol/L (284
      days), or ODCM (474 days) was significantly (P < .0001) shorter than those with <
      50 VPCs (1743 days), NT-proBNP < 900 pmol/L (1743 days), or without disease (1743
      days). NT-proBNP concentration and disease status were independently predictive
      of all-cause mortality. CONCLUSIONS AND CLINICAL IMPORTANCE: The combination of
      NT-proBNP assay and Holter detected ODCM with high accuracy. NT-proBNP and
      disease status were independently associated with survival. NT-proBNP assay
      identified Dobermans with high probability of increased LVIDs consistent with
      ODCM, and can facilitate pursuit of confirmatory diagnostic testing, such as
      echocardiography, in suspected Dobermans.

PMID- 22998091
TI  - The burden of diabetes mellitus and impaired fasting glucose in an urban
      population of Sri Lanka.
AB  - AIMS: To describe the burden of diabetes mellitus and impaired fasting glucose in
      middle-aged residents (35-64 years) in an urban area of Sri Lanka. METHODS: A
      cross-sectional survey was conducted in the Ragama Medical Officer of Health
      area, from which 2986 participants (1349 men and 1637 women) were randomly
      selected from the electoral registry between January and December 2007. The
      participants underwent a physical examination and had their height, weight, waist
      and hip circumferences and blood pressure measured by trained personnel. Fasting
      blood samples were taken for measurement of glucose, HbA(1c)  and lipids. The
      prevalence of diabetes (fasting plasma glucose > 7 mmol/l) and impaired fasting
      glycaemia (fasting plasma glucose 5.6-6.9 mmol/l) and major predictors of
      diabetes in Sri Lanka were estimated from the population-based data. RESULTS: Age
      adjusted prevalence of diabetes mellitus in this urban population was 20.3% in
      men and 19.8% in women. Through the present screening, 263 patients with diabetes
      and 1262 with impaired fasting glucose levels were identified. The prevalence of
      newly detected diabetes was 35.7% of all patients with diabetes. Among patients
      with diabetes, only 23.8% were optimally controlled. In the regression models,
      high BMI, high waist circumference, high blood pressure and hypercholesterolaemia
      increased the fasting plasma glucose concentration, independent of age, sex and a
      family history of diabetes. CONCLUSIONS: Our data demonstrate the heavy burden of
      diabetes in this urban population. Short- and long-term control strategies are
      required, not only for optimal therapy among those affected, but also for
      nationwide primary prevention of diabetes.

PMID- 22998092
TI  - The experience of hope and aging: a hermeneutic photography study.
AB  - The purpose of this hermeneutic photography study was to explore how older adults
      lived hope in their day-to-day lives. A purposive sample of 12 older adults 65
      and older was asked to photograph how they experienced and lived hope in their
      everyday lives. Participants were asked to select four to five photographs that
      best reflected their "lived hope," and these photographs were used as prompts for
      subsequent interviews. Data were analyzed using thematic analysis of the
      interviews and photographs, which revealed that these study participants lived a
      philosophy of hope in which hope provided a kind of landscape through which these
      older adults lived and made sense of their life experiences. Implications for
      helping nurses foster and make hope more visible for their older clients are
      suggested.

PMID- 22998093
TI  - Understanding bereaved family members' dissatisfaction with end-of-life care in
      nursing homes.
AB  - With increasing numbers of older adults identifying a nursing home (NH) as their
      final place of care, it is important to assess the quality of dying in this
      setting and understand factors that impact family members' dissatisfaction with
      end-of-life care. A retrospective bereaved family member survey (N = 208) was
      conducted in 21 NHs located in urban areas of central Canada. Bereaved family
      members who were dissatisfied with care identified significantly more concerns in
      all domains assessed and were more likely to have problems with: (a) receiving
      confusing information from nursing staff about the resident's care, including
      medical treatments; (b) receiving inadequate information from nursing staff; and
      (c) feeling that end-of-life care was different than they had expected. Since the
      quality of communication between nurses, residents, and family members is the
      main factor that determines families' dissatisfaction with care, strategies and
      interventions aimed at reducing unmet information needs will be vital to
      improving end-of-life care in NHs.

PMID- 22998094
TI  - Combined exercise training and self-management education for community-dwelling
      older adults with diabetes in Korea.
AB  - This study examined the effect of a combined program of exercise training and
      self-management education on risk factors for diabetes complications and
      adherence behavior. A two-group, quasi-experimental study design was used to test
      the 12-week intervention program with community-dwelling older adults in Korea.
      Change scores (from baseline to Week 13) of outcome variables were compared
      between the intervention group (n = 21) and the control group (n = 16). The
      change scores in triglyceride levels, body weight, body mass index, and diabetes
      self-management behavior showed significant differences between groups. However,
      no significant differences were found in A1C and blood pressure change scores
      between the groups in this sample, in which these characteristics were relatively
      well controlled at baseline. The results of this study showed some promising
      synergistic effects of lowering cardiovascular risk factors from combining the
      two interventions.

PMID- 22998095
TI  - The use of socially assistive robots for dementia care.
AB  - Innovative solutions for dementia care are required to address the steady rise in
      adults living with dementia, lack of adequate staffing to provide high-quality
      dementia care, and the need for family caregivers to provide care for their loved
      ones in the home. This article provides an overview of the use of socially
      assistive robots (SARs) to offer support as therapists, companions, and educators
      for people living with dementia. Social, ethical, and legal challenges associated
      with the use of robotic technology in patient care and implications for the use
      of SARs by nurses are discussed. These items considered, the authors conclude
      that SARs should be considered as a viable way to assist people living with
      dementia to maintain their highest possible level of independence, enhance their
      quality of life, and provide support to overburdened family caregivers. Further
      research is needed to evaluate the merits of this technological approach in the
      care of adults with dementia.

PMID- 22998096
TI  - Statin drugs: reducing cardiovascular risk in older adults.
AB  - Dyslipidemia is one of the most modifiable risk factors in preventing heart
      disease. Evidence demonstrates that the process of atherosclerosis, a result of
      dyslipidemia, begins in young adults. Initiating statin therapy has been shown to
      reduce the risk of cardiovascular events and mortality. Determining the right
      statin medication and dose for an older adult based on national guidelines can be
      challenging, as multiple factors must be considered in this decision. When
      initiating statin therapy, clinicians should determine the appropriate percentage
      of reduction in low-density lipoprotein cholesterol needed to achieve the target
      goal. Additionally, when changing from one cholesterol-lowering medication to
      another, knowledge of equivalent dosing is important. Generally, statin drugs are
      well tolerated with a good safety profile in older adults but are underused in
      this patient population. Issues such as existing comorbid conditions,
      polypharmacy with the potential for drug-drug interactions, impaired drug
      metabolism, and decreased functional status can contribute to adverse events and
      increase the frequency of myalgias and less frequently, hepatotoxicity.
      Clinicians prescribing statin therapy for older adults need to remain current on
      advances in research regarding potential interactions and contraindications
      within this drug class.

PMID- 22998097
TI  - A palliative care educational intervention for frontline nursing home staff: the
      IMPRESS project.
AB  - The purpose of this study was to examine nursing home staff perceptions of end-of
      life (EOL) care skills after an educational intervention. IMPRESS (IMproving
      PRofessional Education and Sustaining Support) was a quality improvement EOL care
      educational intervention (six lectures on core palliative care concepts) for
      frontline nursing home staff at five community nursing homes. Questionnaires were
      completed to evaluate frequency of application of palliative care skills before
      and after the educational series. Nursing home staff reported applying palliative
      care skills significantly more frequently after the intervention. A significant
      dose-response association was noted between number of inservice sessions attended
      and improvement in scores: Scores increased 0.04 points for staff who attended
      two of the six sessions, 0.12 for four sessions attended, and 0.46 for five to
      six sessions attended (p = 0.03). The results indicate that frontline nursing
      home staff who attend inservice sessions on core palliative care topics can
      significantly increase self-reported application of palliative care skills.

PMID- 22998098
TI  - Relating structure, entropy, and energy of solvation of nanoscale solutes:
      application to gold nanoparticle dispersions.
AB  - Structural estimators for the entropy are combined with an analysis of the
      different contributions to the energy of solvation to understand the molecular
      basis of the thermodynamics of solvation of passivated nanoparticles. Molecular
      dynamics simulations of thiolated gold clusters in ethane are performed over a
      wide range of densities close to the critical isotherm. The entropic changes
      associated with solvent reorganization around the passivated nanoparticle are
      estimated from the nanoparticle-solvent pair correlation function, while the
      entropy of the ligand shell is estimated from the covariance in the positional
      fluctuations of the ligand atoms. The ligand-shell entropy (S(L)) is shown to be
      fairly insensitive to variations in solvent density ranging from vacuum to twice
      the critical density (rho(c)). In contrast, the entropy change due to solvent
      reorganization (DeltaS(ns)(ord)) shows a minimum around the critical point where
      the solvent excess shows a maximum. Combining the entropic estimates with the
      nanoparticle-solvent interaction energies, the free energy of solvation is shown
      to decrease with density once the critical point is crossed in a manner
      qualitatively consistent with available experimental data. The results suggest
      that such an approach to obtain structural insights into the thermodynamics of
      solvation of passivated nanoparticles could be useful in understanding the
      stability of nanoparticle dispersions of widely varying chemistries. This study
      also demonstrates that the theoretical analysis of solvation and self-assembly
      developed in the context of biomolecular hydration can be very usefully extended
      to understand the behavior of inorganic nanoparticle dispersions.

PMID- 22998099
TI  - Gender differences in risk factors for airway symptoms following tracheal
      intubation.
AB  - BACKGROUND: A common complaint after endotracheal intubation is sore throat and
      hoarseness. The aim of this study was to describe gender differences and
      independent risk factors in the development of post-operative sore throat and
      hoarseness after endotracheal intubation in adults. METHODS: This prospective
      cross-sectional observational study was conducted at a university hospital in
      Sweden. A total of 495 patients were included (203 men and 292 women) and
      enrolled from a total of eight different surgical departments. Outcome variables
      were post-operative sore throat and hoarseness evaluated post-operatively in the
      post-anaesthesia care unit. A total of 31 variables were recorded which described
      the intubation process, intraoperative factors as well as the extubation process.
      Bivariate and multivariate analyses were performed. RESULTS: The overall
      incidence of post-operative sore throat was 35% and hoarseness 59%. The results
      show different predictors for men and women in the development of airway
      symptoms. The main risk factor for developing sore throat in men was intubation
      by personnel with < 3 months' work experience. In women, it was endotracheal tube
      size 7.0 and multiple laryngoscopies during intubation. The main risk factors for
      hoarseness were cuff pressure for both men and women, and oesophageal temperature
      probe in women. CONCLUSION: Post-operative sore throat and hoarseness result from
      several factors, and the cause of these symptoms are multifactorial and differs
      by gender. Identification of these factors pre-operatively may increase awareness
      among anaesthesia personnel and possibly reduce the incidence of these minor but
      distressing symptoms.

PMID- 22998100
TI  - Comparison of the overnight metyrapone and glucagon stimulation tests in the
      assessment of secondary hypoadrenalism.
AB  - OBJECTIVE: The insulin tolerance test (ITT) is contraindicated in a proportion of
      patients with suspected ACTH deficiency. The aim of this study was to investigate
      the diagnostic accuracy of the glucagon stress test (GST) compared with the
      overnight metyrapone test (OMT) in patients with contraindications to ITT.
      DESIGN: This was a prospective comparison of the GST to the OMT in patients with
      suspected ACTH deficiency and contraindications to the ITT. The OMT was used as
      the standard for comparison. The study was conducted at two tertiary referral
      centres for pituitary disease. PATIENTS: Seventy-eight patients underwent
      contemporaneous OMT and GST of whom 61 had sufficient suppression of cortisol
      during the OMT to be included in the comparison. Forty had suffered traumatic
      brain injury, 36 had organic pituitary disorders and two were classified as
      'other'. MEASUREMENTS: ACTH sufficiency was defined as 0800h 11-deoxycortisol >=
      200 nmol/l on OMT and peak cortisol >= 440 nmol/l on GST, as per local reference
      ranges. RESULTS: There was significant discrepancy between the proportion of
      patients diagnosed with ACTH deficiency using the OMT (39%) and GST (89%). From
      our data, a GST peak cortisol cut-off of >=350 nm provides the combination of
      optimal sensitivity (71%) and specificity (57%), compared with a higher
      sensitivity (88%) but poor specificity (11%) using a cut-off of >=440 nm.
      CONCLUSIONS: The GST should be used with caution as a diagnostic test of ACTH
      reserve. The OMT should be used in preference to the GST to assess the
      hypothalamic pituitary adrenal axis where ITT is contraindicated.

PMID- 22998101
TI  - 1,3,4-Oxadiazole containing silanes as novel hosts for blue phosphorescent
      organic light emitting diodes.
AB  - Five rigid oxadiazole (OXD) containing silanes, denoted 1-5, have been developed
      with high morphological stability. Disruption of the pi-aromatic conjugation by
      introduction of Si atoms leads to a large band gap and high triplet energy. Among
      the OXDs we studied, 2,5-bis(triphenylsilylphenyl)-1,3,4-oxadiazole 5 is the best
      host for FIrpic, with a phosphorescent organic light emitting diode (PHOLED) turn
      on voltage of 6.9 V, maximum luminance of 5124 cd/m(2), current efficiency of
      39.9 cd/A, and external quantum efficiency of 13.1%. Special molecular stacking
      in the single crystal of 5 was discussed.

PMID- 22998102
TI  - Abstracts of the EAU Robotic Urology Section Congress, ERUS 2012. London, United
      Kingdom. September 26-28, 2012.

PMID- 22998103
TI  - Correlation between components of newly diagnosed exudative age-related macular
      degeneration lesion and focal retinal sensitivity.
AB  - PURPOSE: To analyse lesion components determining retinal sensitivity in
      microperimetry in eyes with newly diagnosed exudative age-related macular
      degeneration (AMD). METHODS: Visual acuity, contrast sensitivity, microperimetry,
      optical coherence tomography (OCT), and fluorescein (FA) and indocyanine green
      (ICGA) angiographies of 23 eyes of 23 patients were analysed. Central
      microperimetry grids with 28 test stimulus sites were automatically aligned with
      three-dimensional OCTs and manually aligned with angiographies. Thicknesses of
      the neuroretina, neuroepithelial detachment (NED), retinal pigment epithelial
      (RPE) elevation and subretinal tissue were measured under the 644 microperimetry
      stimulus sites. Areas of classic and occult choroidal neovascularizations (CNVs),
      subretinal and intraretinal haemorrhage, and late hyperfluorescence in ICGA were
      identified. The impact of the lesion components on retinal sensitivity was
      evaluated with correlation analysis and multivariate modelling. RESULTS:
      Decreased retinal sensitivity correlated significantly with the presence of CNV,
      haemorrhage, subretinal tissue and RPE elevation. Out of the OCT parameters, the
      most important determinant of sensitivity was the thickness of RPE elevation
      (Spearman's rho, r = -0.202, p < 0.0001). The thicknesses of subretinal tissue (r
      = -0.168, p < 0.0001) and NED had weaker effects (r = -0.147, p < 0.0001), and
      the neuroretinal thickness remained nonsignificant. In multivariate modelling,
      RPE elevation and subretinal tissue in OCT, CNV membranes in angiographies and
      haemorrhage had the strongest impacts on retinal sensitivity. CONCLUSION: The
      most important lesion components affecting retinal function were RPE elevation
      and subretinal tissue in OCT as well as neovascular membranes and haemorrhage in
      angiographies. NED and neuroretinal thickening remained less significant.

PMID- 22998104
TI  - Evaluation of a sieve classification method for characterization of low-dose
      interactive mixtures.
AB  - This study investigated a sieve classification method for evaluating carrier
      materials and particle size fractions, which could be a valuable tool in the
      early development of pharmaceutical dosage forms containing low-dose interactive
      mixtures. When developing new products based on interactive mixtures, it is
      essential to ensure that the drug particles are successfully deagglomerated and
      have adhered to the carrier particles. In this study, the effect on the demixing
      potential (DP) of low-dose interactive mixtures was assessed for various carrier
      particle sizes and surface textures. The model drug used was sodium salicylate
      and the tested carriers were lactose, mannitol, and isomalt. The results showed
      that the lowest DPs, i.e. the most mechanically stable mixtures, were obtained
      with lactose. Furthermore, for interactive mixtures, small carrier particles
      and/or a narrow carrier particle size range are essential for obtaining a low DP
      and high homogeneity. Calculation of the DP provided a reliable estimate of the
      quality of the low-dose interactive mixtures used in this study. 

PMID- 22998105
TI  - Cognitive decline in elderly bipolar disorder patients: a follow-up study.
AB  - OBJECTIVE: Older individuals with bipolar disorder may exhibit greater cognitive
      decline over time compared to mentally healthy elderly individuals. We aimed to
      investigate neurocognitive performance in bipolar disorder over a period of two
      years. METHODS: A comprehensive neuropsychological test battery was applied at
      baseline and two years later to 65 euthymic elderly outpatients with bipolar
      disorder (mean age = 68.35, range: 60-90 years) and to a demographically
      comparable sample of 42 healthy elderly controls. A general linear model was used
      to measure changes over time for the two groups. The impact of baseline illness
      characteristics on intra-individual change in neurocognitive performance within
      the bipolar group was studied by using logistic regression analysis. RESULTS: At
      baseline and at follow up, bipolar disorder patients performed worse on all
      neurocognitive measures compared to the healthy elderly group. However, there was
      no significant group-by-time interaction between the bipolar disorder patients
      and the comparison group. CONCLUSIONS: Although older bipolar disorder patients
      have worse cognitive function than normal controls, they did not have greater
      cognitive decline over a period of two years.

PMID- 22998106
TI  - Contemplating the effect on blood availability if the interdonation interval of
      56 days is prolonged.

PMID- 22998107
TI  - Chain-walking strategy for organic synthesis: catalytic cycloisomerization of 1,n
      dienes.
AB  - The catalytic construction of carbon-carbon bonds in small organic molecules via
      chain walking is described. Catalytic cycloisomerization of 1,n-dienes via chain
      walking was achieved using a palladium-1,10-phenanthroline catalyst to form five
      membered-ring products. By means of a cycloisomerization/hydrogenation protocol,
      1,7- to 1,14-dienes were selectively converted to bicyclo[4.3.0]nonane
      derivatives. The use of chain walking provides a new method in organic synthesis
      to functionalize unreactive carbon-hydrogen bonds by letting the catalyst look
      for preferable bond-forming sites by moving around on the substrate.

PMID- 22998108
TI  - Hypercrosslinked large surface area porous polymer monoliths for hydrophilic
      interaction liquid chromatography of small molecules featuring zwitterionic
      functionalities attached to gold nanoparticles held in layered structure.
AB  - A novel approach to porous polymer monoliths hypercrosslinked to obtain large
      surface areas and modified with zwitterionic functionalities through the
      attachment of gold nanoparticles in a layered architecture has been developed.
      The capillary columns were used for the separation of small molecules in
      hydrophilic interaction liquid chromatography mode. First, a monolith with a very
      large surface area of 430 m(2)/g was prepared by hypercrosslinking from a generic
      poly(4-methylstyrene-co-vinylbenzyl chloride-co-divinylbenzene) monolith via a
      Friedel-Crafts reaction catalyzed with iron chloride. Free radical bromination
      then provided this hypercrosslinked monolith with 5.7 at % Br that further
      reacted with cystamine under microwave irradiation, resulting in a product
      containing 3.8 at % sulfur. Clipping the disulfide bonds with tris(2
      carboxylethyl) phosphine liberated the desired thiol groups that bind the first
      layer of gold nanoparticles. These immobilized nanoparticles were an intermediate
      ligand enabling the attachment of polyethyleneimine as a spacer followed by
      immobilization of the second layer of gold nanoparticles which were eventually
      functionalized with zwitterionic cysteine. This layered architecture, prepared
      using 10 nm nanoparticles, contains 17.2 wt % Au, more than twice than that found
      in the first layer alone. Chromatographic performance of these hydrophilic
      monolithic columns was demonstrated with the separation of mixtures of
      nucleosides and peptides in hydrophilic interaction chromatography (HILIC) mode.
      A column efficiency of 51,000 plates/m was achieved for retained analyte
      cytosine.

PMID- 22998109
TI  - Better cancer biomarker discovery through better study design.
AB  - BACKGROUND: High-throughput laboratory technologies coupled with sophisticated
      bioinformatics algorithms have tremendous potential for discovering novel
      biomarkers, or profiles of biomarkers, that could serve as predictors of disease
      risk, response to treatment or prognosis. We discuss methodological issues in
      wedding high-throughput approaches for biomarker discovery with the case-control
      study designs typically used in biomarker discovery studies, especially focusing
      on nested case-control designs. METHODS: We review principles for nested case
      control study design in relation to biomarker discovery studies and describe how
      the efficiency of biomarker discovery can be effected by study design choices. We
      develop a simulated prostate cancer cohort data set and a series of biomarker
      discovery case-control studies nested within the cohort to illustrate how study
      design choices can influence biomarker discovery process. RESULT: Common elements
      of nested case-control design, incidence density sampling and matching of
      controls to cases are not typically factored correctly into biomarker discovery
      analyses, inducing bias in the discovery process. We illustrate how incidence
      density sampling and matching of controls to cases reduce the apparent
      specificity of truly valid biomarkers 'discovered' in a nested case-control
      study. We also propose and demonstrate a new case-control matching protocol, we
      call 'antimatching', that improves the efficiency of biomarker discovery studies.
      CONCLUSIONS: For a valid, but as yet undiscovered, biomarker(s) disjunctions
      between correctly designed epidemiologic studies and the practice of biomarker
      discovery reduce the likelihood that true biomarker(s) will be discovered and
      increases the false-positive discovery rate.

PMID- 22998110
TI  - Synthesis of protected benzenepolyselenols.
AB  - Previously unknown benzenepolyselenols have been synthesized and isolated in
      their acetyl-protected form. The two molecules 1,3,5-tris(acetylseleno)benzene
      and 1,2,4,5-tetrakis(acetylseleno)benzene were synthesized by the reductive
      dealkylation in Na/NH(3) of 1,3,5-tris(tert-butylseleno)benzene and 1,2,4,5
      tetrakis(tert-butylseleno)benzene, respectively. Hexakis(tert-butylseleno)benzene
      was also synthesized and structurally characterized by single-crystal X-ray
      diffraction, but it was not possible to isolate hexakis(acetylseleno)benzene. The
      synthetic methodology is likely to be useful in the synthesis of other
      areneselenols.

PMID- 22998112
TI  - Design of a prospective clinical study on the agreement between the Continuous
      GlucoseMonitor, a novel device for CONTinuous ASSessment of blood GLUcose levels,
      and the RAPIDLab(r) 1265 blood gas analyser: The CONTASSGLU study.
AB  - BACKGROUND: Although a device is needed to continuously measure blood glucose
      levels within an intensive care setting, and several large-scale prospective
      studies have shown that patients might benefit from intensive insulin, potassium,
      or glucose therapy during intensive care, no devices are currently available to
      continuously assess blood glucose levels in critically ill patients. We conceived
      the study described here to evaluate the clinical use of the Continuous Glucose
      Monitor (CGM) performed via a central vein, and to determine the impact of
      phenomena, such as drift and shift, on the agreement between the CGM and a
      RAPIDLab(r) 1265 blood gas analyser (BGA). METHODS/DESIGN: In the CONTinuous
      ASSessment of blood GLUcose (CONTASSGLU) study, up to 130 patients under
      intensive care will be fitted with the CGM, an ex vivo device that continuously
      measures blood glucose and lactate levels. Readings from the device taken 8 h
      after initial placement and calibration will be compared with values measured by
      a BGA. For this study, we chose the BGA as it is an established standard point-of
      care device, instead of the devices used in certified central laboratories.
      Nevertheless, we will also independently compare the results from the point-of
      care BGA with those determined by a central laboratory-based device. Blood
      samples will be collected from each patient from the same site in which the CGM
      will measure blood glucose. Consequently, each participant will serve as their
      own control, and no randomisation is necessary. The 95% limits of agreement and
      the corresponding confidence intervals will be calculated and compared with a
      prespecified clinically acceptable relative difference of 20%. DISCUSSION:
      Several attempts have been made to develop a device to continuously measure blood
      glucose levels within an intensive care setting or to use the devices that were
      originally designed for diabetes management, as several of these devices are
      already available. However, none of these devices were successful in intensive
      care settings. CONTASSGLU may well bridge this gap by confirming the ability of
      the CGM to continuously measure blood glucose levels in intensive care settings.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01580176.

PMID- 22998111
TI  - [PSI(+) ] prion variant establishment in yeast.
AB  - Differences in the clinical pathology of mammalian prion diseases reflect
      distinct heritable conformations of aggregated PrP proteins, called prion
      strains. Here, using the yeast [PSI(+) ] prion, we examine the de novo
      establishment of prion strains (called variants in yeast). The [PSI(+) ] prion
      protein, Sup35, is efficiently induced to take on numerous prion variant
      conformations following transient overexpression of Sup35 in the presence of
      another prion, e.g. [PIN(+) ]. One hypothesis is that the first [PSI(+) ] prion
      seed to arise in a cell causes propagation of only that seed's variant, but that
      different variants could be initiated in different cells. However, we now show
      that even within a single cell, Sup35 retains the potential to fold into more
      than one variant type. When individual cells segregating different [PSI(+) ]
      variants were followed in pedigrees, establishment of a single variant phenotype
      generally occurred in daughters, granddaughters or great-granddaughters - but in
      5% of the pedigrees cells continued to segregate multiple variants indefinitely.
      The data are consistent with the idea that many newly formed prions go through a
      maturation phase before they reach a single specific variant conformation. These
      findings may be relevant to mammalian PrP prion strain establishment and
      adaptation.

PMID- 22998113
TI  - Functional properties of protein isolates from Caragana korshinskii Kom.
      extracted by three different methods.
AB  - Seeking cheap, sustainable protein sources greatly facilitates in alleviating the
      dependence upon expensive animal-based protein in many developing countries. 
      Caragana korshinskii  Kom. offers a good alternative feedstock because of its
      high-content of protein, low fertilizer and pesticide requirements, excellent
      stress (high salty and less water) tolerance, wide adaptability, etc. The
      functional properties of  C. korshinskii  Kom. protein isolates by three
      different extraction methods were investigated. The extraction processes greatly
      influenced the physiological characteristics of protein isolates.  C. korshinskii
      Kom. protein isolate by traditional alkaline extraction (Al-CPI) exhibited good
      performance on emulsifying activity index, oil and water absorption capacity, and
      foaming property compared to A-CPI ( C. korshinskii  Kom. protein isolate by the
      acetone precipitation method) and TCA-CPI ( C. korshinskii  Kom. protein isolate
      by trichloroacetic acid-acetone precipitation). The water and oil adsorption
      capacities of Al-CPI were observed at 4.99 and 3.45 g/g, respectively, even much
      higher than those of soy protein isolate (SPI) (3.94 and 2.95 g/g, respectively).
      The highest foaming capacity was observed by Al-CPI at 185.0%, followed by A-CPI
      (177.5%), TCA-CPI (142.5%), and SPI (141.9%), respectively. It has to be noted
      that A-CPI showed good solubility at acidic pH and excellent in vitro
      digestibility. After sequential pepsin-trypsin digestion, the percentage of N
      release of A-CPI reached up to 83.7%, which was 1.63 times that of Al-CPI
      (51.2%), 1.19 times that of TCA-CPI (70.1%), and slightly higher than that of the
      commercial SPI (82.5%). These results indicate that  C. korshinskii  Kom. holds
      great potential for application in the animal feed and food additive industry.

PMID- 22998114
TI  - Cutaneous composite hemangioendothelioma on the nose treated with electron beam.

PMID- 22998115
TI  - A theory for the morphological dependence of wetting on a physically patterned
      solid surface.
AB  - We present a theoretical model for predicting equilibrium wetting configurations
      of two-dimensional droplets on periodically grooved hydrophobic surfaces. The
      main advantage of our model is that it accounts for pinning/depinning of the
      contact line at step edges, a feature that is not captured by the Cassie and
      Wenzel models. We also account for the effects of gravity (via the Bond number)
      on various wetting configurations that can occur. Using free-energy minimization,
      we construct phase diagrams depicting the dependence of the wetting modes
      (including the number of surface grooves involved in the wetting configuration)
      and their corresponding contact angles on the geometrical parameters
      characterizing the patterned surface. In the limit of vanishing Bond number, the
      predicted wetting modes and contact angles become independent of drop size if the
      geometrical parameters are scaled with drop radius. Contact angles predicted by
      our continuum-level theoretical model are in good agreement with corresponding
      results from nanometer-scale molecular dynamics simulations. Our theoretical
      predictions are also in good agreement with experimentally measured contact
      angles of small drops, for which gravitational effects on interface deformation
      are negligible. We show that contact-line pinning is important for
      superhydrophobicity and that the contact angle is maximized when the droplet size
      is comparable to the length scale of the surface pattern.

PMID- 22998116
TI  - Watching the paint dry at work: psychometric examination of the Dutch Boredom
      Scale.
AB  - Boredom at work is a state of employee unwell-being that is characterized by
      relatively low arousal and high dissatisfaction. At present little is known about
      boredom at work. In order to facilitate future research, the current study
      introduces a brief self-report questionnaire that assesses boredom at work, the
      Dutch Boredom Scale (DUBS). We argue that (1) boredom at work can be
      distinguished empirically from related concepts such as work engagement and job
      burnout; (2) boredom at work results from having an unchallenging, "passive" job;
      and (3) the subsequent lack of challenge in the form of boredom may result in
      dissatisfaction with the job and with the organization. Using data from 6315
      employees, factor analysis supported the factorial and discriminant validity of
      the DUBS vis-a-vis engagement and burnout. As expected, structural equation
      modeling revealed that demands and resources were negatively associated with
      boredom. Moreover, boredom at work was negatively related with job satisfaction
      and organizational commitment, and positively with turnover intention. These
      findings support the validity of the DUBS. Future research may focus on
      underemployment as an antecedent of boredom at work, and on the effects of
      boredom on job performance. 

PMID- 22998117
TI  - In vitro bioactivation of a selective estrogen receptor modulator (2S,3R)-(+)-3
      (3-hydroxyphenyl)-2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4
      benzoxathiin-6-ol (I) in liver microsomes: formation of adenine adducts.
AB  - As part of our efforts to develop safer selective estrogen receptor modulators
      (SERMs), compound I {(2S,3R)-(+)-3-(3-hydroxyphenyl)-2-[4-(2-pyrrolidin-1
      ylethoxy)-phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol} was previously identified as
      a lead for further development. Subsequent studies showed that compound I is
      genotoxic in both in vitro Chinese hamster ovary (CHO) cells and in vivo mouse
      studies. To better understand the possible mechanisms for the observed
      genetoxicity effects, in vitro incubations of I with liver microsomes of human,
      monkey, and mouse in the presence of adenine were performed, which led to the
      detection of five adenine adducts. The formation of these adducts was NADPH
      dependent, suggesting the involvement of oxidative bioactivation catalyzed by
      cytochrome P450 enzymes. The mechanism for the formation of the major adenine
      adduct (A1) involves the formation of a reactive ring-opened para-quinone
      intermediate. The formation of four other adenine adducts may involve the
      formation of a reactive epoxide or ortho-quinone intermediate. Furthermore,
      incubations of compound I with human hepatocytes showed dose-dependent DNA
      damages in Comet assays. All of the above suggest that some reactive metabolites
      of compound I, formed through bioactivation mechanisms, have a potential to
      interact with DNA molecules in vitro and in vivo. This may be one of the causes
      of the genotoxicity observed preclinically both in vitro and in vivo. This case
      study demonstrated an approach using in vitro DNA trapping assays for assessing
      the genotoxicity potential of drug candidates.

PMID- 22998120
TI  - Why the solvation water around proteins is more dense than bulk water.
AB  - The main aim of this work is to propose a rational explanation of the commonly
      observed phenomenon of increasing water density within solvation shell of
      proteins. We have observed that the geometry of the water-water hydrogen bond
      network within solvation layer differs from the one in bulk water, and it is the
      result of interactions of water molecules with protein surface. Altered geometry
      of the network reflects changes in the structure of solvation water. Our
      explanation of the observed changes is based on model proposed by Tanaka (Tanaka,
      H. J. Chem. Phys. 2000, 112, 799). According to this model, in liquid water exist
      some special structures formed by water molecules thanks to their unique ability
      to create the branched network of hydrogen bonds. These structures have two
      characteristic features: a low potential energy of internal interactions and a
      large specific volume. We provide some evidence for the supposition that
      deformation of the geometry of the water-water hydrogen bond network is
      responsible for destabilization of these structures and therefore for increased
      local density of water. Our model is constructed on the basis of the analysis of
      solvation water of some specific protein, the motor head of kinesin.
      Subsequently, we used it for description of solvation of purely hydrophobic
      surface. It has been found that in this case an unoccupied space between the
      hydrophobic surface and neighboring solvation layer exists. It has been found
      that thickness of this region depends on local geometry of the water-protein
      interface, and it is a result of maintaining a balance between water-surface
      interactions and water-water interactions. In our opinion, existence of this
      space region is one of the main factors that differentiates the hydrophobic
      hydration from hydration of the native form of kinesin. Its existence also
      explains why the density is greater for solvation water around the native form of
      the protein than in the vicinity of the hydrophobic surface.

PMID- 22998121
TI  - Historical stocking data and 19th century DNA reveal human-induced changes to
      native diversity and distribution of cutthroat trout.
AB  - Many species are threatened with extinction and efforts are underway worldwide to
      restore imperilled species to their native ranges. Restoration requires knowledge
      of species' historical diversity and distribution. For some species, many
      populations were extirpated or individuals moved beyond their native range before
      native diversity and distribution were documented, resulting in a lack of
      accurate information for establishing restoration goals. Moreover, traditional
      taxonomic assessments often failed to accurately capture phylogenetic diversity.
      We illustrate a general approach for estimating regional native diversity and
      distribution for cutthroat trout in the Southern Rocky Mountains. We assembled a
      large archive of historical records documenting human-mediated change in the
      distribution of cutthroat trout (Oncorhynchus clarkii) and combined these data
      with phylogenetic analysis of 19th century samples from museums collected prior
      to trout stocking activities and contemporary DNA samples. Our study of the trout
      in the Southern Rocky Mountains uncovered six divergent lineages, two of which
      went extinct, probably in the early 20th century. A third lineage, previously
      declared extinct, was discovered surviving in a single stream outside of its
      native range. Comparison of the historical and modern distributions with stocking
      records revealed that the current distribution of trout largely reflects
      intensive stocking early in the late 19th and early 20th century from two
      phylogenetically and geographically distinct sources. Our documentation of recent
      extinctions, undescribed lineages, errors in taxonomy and dramatic range changes
      induced by human movement of fish underscores the importance of the historical
      record when developing and implementing conservation plans for threatened and
      endangered species.

PMID- 22998122
TI  - Latest advances in predicting DILI in human subjects: focus on biomarkers.
AB  - INTRODUCTION: The quest for a biomarker that would reliably identify patients at
      risk of developing acute drug-induced liver injury (DILI) to a specific agent or
      class of agents before it occurs, has been underway for years. Historical host
      factors for DILI, such as older age and female gender, are not considered
      sufficient to truly predict an individual's inherent risk of DILI. In vitro and
      animal-based biomarker discoveries, in many instances, have not been considered
      accurate enough for drug development in human subjects nor for use in clinical
      practice. AREAS COVERED: In order to assess the current state of biomarkers to
      predict idiosyncratic human DILI, the authors utilized the PubMed literature
      search tool to identify research reports dealing with clinical DILI biomarkers
      covering the period of 2010 through to June 2012. Studies involving
      pharmacogenetic, proteomic and toxicogenomic analyses are preferentially
      reviewed. EXPERT OPINION: Although acute DILI has been linked to specific genetic
      associations (e.g., flucloxacillin and HLA-B*5701; and certain polymorphisms seen
      with anti-TB agent DILI), such predictors have been able to identify only some
      patients at risk for only a limited number of drugs. Proteomic-based biomarkers
      from stored sera in the US DILI Network, such as apolipoprotein E, have been
      identified as potential candidates, but require further study. As it currently
      stands, the quest for a widely applicable, validated DILI biomarker remains an
      ongoing clinical challenge.

PMID- 22998123
TI  - Palladium-catalyzed allylic fluorination of cinnamyl phosphorothioate esters.
AB  - A highly regioselective, Pd-catalyzed allylic fluorination of phosphorothioate
      esters is reported. This chemistry addresses several limitations of previously
      reported methods in which elimination and lack of reactivity were problematic.
      Preliminary mechanistic investigations reveal that these reactions are
      stereospecific and provide fluorinated products with net retention of
      stereochemical configuration. In analogy to other Pd-catalyzed allylic
      substitution reactions, this process likely proceeds through a palladium pi-allyl
      intermediate.

PMID- 22998124
TI  - Risk factors related to lifetime suicide attempts in acutely admitted bipolar
      disorder inpatients.
AB  - OBJECTIVE: The main aim of this study was to assess possible clinical
      characteristics of acutely admitted bipolar I disorder (BD-I) and bipolar II
      disorder (BD-II) inpatients at high risk of suicide by comparing patients who had
      made one or several serious suicide attempts with patients who had not. METHODS:
      A total of 206 consecutive patients (mean age 42 +/- 15 years; 54.9% women) with
      DSM-IV diagnosed BD-I (n = 140) and BD-II (n= 66) acutely admitted to a single
      psychiatric hospital department from November 2002 through June 2009 were
      included. Using a detailed retrospective questionnaire, patients with a history
      of a serious suicide attempt were compared to those with no history of a suicide
      attempt. RESULTS: Ninety-three patients (45.1%) had a history of one or more
      serious suicide attempts. These constituted 60 (42.9%) of the BD-I patients and
      33 (50%) of the BD-II patients (no significant difference). Lifetime suicide
      attempt was associated with a higher number of hospitalizations due to depression
      (p < 0.0001), antidepressant (AD)-induced hypomania/mania (p = 0.033), AD- and/or
      alcohol-induced affective episodes (p = 0.009), alcohol and/or substance use (p =
      0.002), and a family history of alcohol abuse and/or affective disorder (p =
      0.01). Suicide attempt was negatively associated with a higher Positive and
      Negative Syndrome Scale for Schizophrenia (PANSS) Positive Subscale score (p =
      0.022) and more hospitalizations due to mania (p = 0.006). CONCLUSIONS: The
      lifetime suicide attempt rate in BD inpatients is high. Risk factors of suicide
      attempts were: (i) a predominant depressive course of illness, (ii) comorbid
      alcohol and substance use disorders, and (iii) a history of AD- and/or alcohol
      induced affective episodes. Risk-reducing factors were a preponderant manic or
      psychotic course of the illness. These risk factors may be signs of a clinical
      subgroup at risk of suicidal behaviour, and seem to be important for suicide risk
      assessment in acutely admitted BD patients.

PMID- 22998125
TI  - Perivesical fat invasion in bladder cancer: implications for prognosis comparing
      pT2b, pT3a and pT3b stages and consequences for adjuvant chemotherapy
      indications.
AB  - Study Type--Therapy (retrospective cohort) Level of Evidence 2b. What's known on
      the subject? and What does the study add? The more that bladder cancer progresses
      from the urothelium to the outside of the bladder the worse the prognosis. To
      date, the use of adjuvant chemotherapy has not been completely defined. The
      present study clarifies the prognosis and benefits of adjuvant chemotherapy for
      different stages of bladder cancer that invade perivesical fat. OBJECTIVE: * To
      assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical
      cystectomy (RC) in order to define potential situations where chemotherapy may be
      of benefit. PATIENTS AND METHODS: * Between 1985 and 2009, 903 patients underwent
      a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre. *
      In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour,
      and 129 patients (14.3%) a pT3b tumour. * The median (range) overall follow-up
      was 23 (1-350) months. * Overall (OS), disease-specific (DSS), metastases-free
      (MFS) and local recurrence-free survival (LRFS) was estimated and compared using
      Kaplan-Meier plots and log-rank test. RESULTS: * The 5-year survivals pT2b and
      pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and
      OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%,
      44%, 40%, and 31% respectively). * In pN0 disease, MFS differences between pT2b
      pT3a and pT3b tumours were not significant in patients who had received adjuvant
      chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant
      in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%,
      respectively). CONCLUSIONS: * Bladder cancers invading perivesical tissue
      macroscopically have a greater propensity to produce lymph node metastases, local
      recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may
      receive more benefit from adjuvant chemotherapy. * Our results could be a useful
      for selecting patients for adjuvant chemotherapy.

PMID- 22998126
TI  - Selecting anti-epileptic drugs: a pediatric epileptologist's view, a computer's
      view.
AB  - OBJECTIVE: To identify which clinical characteristics are important to include in
      clinical decision support systems developed for Antiepileptic Drug (AEDs)
      selection. METHODS: Twenty-three epileptologists from the Childhood Absence
      Epilepsy network completed a survey related to AED selection. Using cluster
      analysis their responses where classified into subject matter groups and weighted
      for importance. RESULTS: Five distinct subject matter groups were identified and
      their relative weighting for importance were determined: disease characteristics
      (weight 4.8 +/- 0.049), drug toxicities (3.82 +/- 0.098), medical history (3.12
      +/- 0.102), systemic characteristics (2.57 +/- 0.048) and genetic characteristics
      (1.08 +/- 0.046). CONCLUSION: Research about prescribing patterns exists but
      research on how such data can be used to train advanced technology is novel. As
      machine learning algorithms becomes more and more prevalent in clinical decisions
      support systems, developing methods for determining which data should be part of
      those algorithms is equally important.

PMID- 22998127
TI  - Association of dietary copper and zinc levels with hepatic copper and zinc
      concentration in Labrador Retrievers.
AB  - BACKGROUND: Copper-associated hepatitis is an inherited disease in the Labrador
      Retriever. Apart from genetic factors, dietary intake of copper and zinc are
      suspected to play a role in the pathogenesis. OBJECTIVES: To investigate whether
      dietary copper and zinc levels of commercially available dry diets are associated
      with hepatic copper and zinc concentrations in Labrador Retrievers. ANIMALS:
      Fifty-five Labrador Retrievers that were fed a single brand and type of
      commercial dry food for at least 1 year. Of these, 44 dogs were family members of
      Labrador Retrievers with copper-associated hepatitis. METHODS: Liver biopsies,
      blood samples, and diet samples were obtained. Liver specimens were scored
      histologically and copper and zinc concentrations were quantified. Dietary
      concentrations of copper and zinc were measured. The association between dietary
      intake of copper and zinc and hepatic copper and zinc concentrations was
      investigated by linear regression analysis. RESULTS: High dietary copper and low
      dietary zinc levels were significantly associated with high hepatic copper
      levels. No association between dietary intake and hepatic zinc was present.
      CONCLUSIONS AND CLINICAL RELEVANCE: Dietary copper and zinc at current levels in
      commercially available dry dog food can influence hepatic copper and can be a
      risk factor for the development of copper-associated hepatitis in Labrador
      Retrievers with a genetic susceptibility to copper.

PMID- 22998128
TI  - Bacterial mechanisms of reversible protein S-thiolation: structural and
      mechanistic insights into mycoredoxins.
AB  - Mycobacteria produce millimolar concentrations of mycothiol (MSH) as their major
      low molecular weight thiol redox buffer. MSH-deficient mutants display increased
      sensitivity towards reactive oxygen, nitrogen and electrophilic species as well
      as alkylating agents and antibiotics. MSH is maintained in its reduced thiol
      state by the NADPH-dependent mycothiol disulphide reductase (Mtr). However, the
      redoxin that uses the MSH/Mtr/NADPH pathway for reduction of MSH-mixed protein
      disulphides, formed during oxidative stress, has long remained unknown. In this
      issue, Van Laer et al. report that MSH provides the reducing power for
      mycoredoxin-1 (Mrx1) in reduction of synthetic MSH-mixed disulphides. The reduced
      (dithiol) and oxidized (disulphide) solution structures of Mrx1 have been solved
      by nuclear magnetic resonance (NMR) spectroscopy. NMR time course experiments
      have also demonstrated the transient S-mycothiolation of the active site Cys14 of
      oxidized Mrx1 during reduction by the MSH/Mtr/NADPH electron pathway. The paper
      opens a new era of research to identify S-mycothiolated Mrx1 substrates and the
      function of MSH in redox regulation and virulence in Mycobacterium tuberculosis.

PMID- 22998130
TI  - Response to Nandakoban et al. Acute tubulointerstitial nephritis following
      treatment with exenatide.

PMID- 22998129
TI  - Comparative cost-effectiveness of interventions to improve medication adherence
      after myocardial infarction.
AB  - OBJECTIVE: To evaluate the comparative cost-effectiveness of interventions to
      improve adherence to evidence-based medications among postmyocardial infarction
      (MI) patients. DATA SOURCES/STUDY SETTING: Cost-effectiveness analysis. STUDY
      DESIGN: We developed a Markov model simulating a hypothetical cohort of 65-year
      old post-MI patients who were prescribed secondary prevention medications. We
      evaluated mailed education, disease management, polypill use, and combinations of
      these interventions. The analysis was performed from a societal perspective over
      a lifetime horizon. The main outcome was an incremental cost-effectiveness ratio
      (ICER) as measured by cost per quality-adjusted life year (QALY) gained. DATA
      COLLECTION/EXTRACTION METHODS: Model inputs were extracted from published
      literature. PRINCIPAL FINDINGS: Compared with usual care, only mailed education
      had both improved health outcomes and reduced spending. Mailed education plus
      disease management, disease management, polypill use, polypill use plus mailed
      education, and polypill use plus disease management cost were $74,600, $69,200,
      $133,000, $113,000, and $142,900 per QALY gained, respectively. In an incremental
      analysis, only mailed education had an ICER of less than $100,000 per QALY and
      was therefore the optimal strategy. Polypill use, particularly when combined with
      mailed education, could be cost effective, and potentially cost saving if its
      price decreased to less than $100 per month. CONCLUSIONS: Mailed education and a
      polypill, once available, may be the cost-saving strategies for improving post-MI
      medication adherence.

PMID- 22998131
TI  - Human T-lymphotropic virus laboratory testing of maternal blood at time of cord
      blood donations and clinical implications.
AB  - BACKGROUND: In the United States, blood products are tested for infectious
      diseases including human T-lymphotropic virus (HTLV)-I/II. Positive results of
      maternal blood samples at the time of cord blood (CB) donation must be reported
      to mother and physician. Tests for HTLV have a high false-positive rate. This is
      problematic because there is no prenatal testing of the mother. STUDY DESIGN AND
      METHODS: This study involves 119,769 maternal blood samples at time of CB
      donation and evaluates positive results for HTLV in screening tests, supplemental
      immunoassays, and nucleic acid tests (NATs). Infectious disease markers (IDMs)
      and maternal health histories of HTLV-positive and -negative mothers were
      compared. RESULTS: Of 119,769 mothers donating CB, 545 tested positive with the
      screening test, 33 were positive with the supplemental tests, and two were
      positive with NAT. When indeterminate results were excluded from the supplemental
      test only six were positive. Eight of 34 mothers with positive or indeterminate
      supplemental test results had received intravenous immunoglobulin. There were no
      significant differences between HTLV-positive and -negative mothers with regard
      to the incidence of other IDMs. CONCLUSIONS: Testing maternal blood for HTLV is
      problematic for CB banks, obstetricians, and mothers because of the high false
      positive rate. CB banks need rapid turnaround time and supplemental testing. If
      results on the latter are positive the obstetrician should be notified, educated,
      do follow-up testing, and counseling. Indeterminate results on supplemental tests
      are most likely false positives. We recommend that mothers with positive or
      indeterminate supplemental test results have follow-up NAT.

PMID- 22998132
TI  - Acute conjunctivitis caused by Ewingella americana.
AB  - The first case of Ewingella americana conjunctivitis in an otherwise healthy
      child is reported. Cultures of the conjunctival purulent exudate taken from both
      eyes grew E. americana. The infection resolved completely after successful
      treatment with amoxicillin/clavulanate. E. americana should be considered a rare
      but potential pathogen causing conjunctivitis.

PMID- 22998133
TI  - Diffusion of macromolecules through sclera.
AB  - PURPOSE: To quantify the in vitro permeability coefficient over different
      topographical locations of porcine sclera to macromolecules with different
      molecular weight. METHODS: Fresh equatorial and posterior superotemporal porcine
      sclera was mounted in a two-chamber diffusion apparatus, and its permeability to
      fluorescein isothiocyanate (FITC)-conjugated dextrans ranging in molecular weight
      from 40 kDa to 150 kDa was determined by fluorescence spectrophotometry. The
      sclera was processed as frozen sections and viewed with a fluorescence
      microscope. The thickness of the area and the thickness that macromolecules
      enriched in the surface of sclera were measured. RESULTS: The permeability
      coefficient (Pc) of porcine sclera to macromolecules was significantly higher (40
      kDa, p = 0.028; 70 kDa, p = 0.033; 150 kDa, p = 0.007) in equatorial region than
      posterior, which could be attributed to the significant difference of thickness
      (p < 0.001, Kruskal-Wallis) between them. Moreover, linear regression indicated a
      significant negative relationship (40 kDa, p < 0.001; 70 kDa, p = 0.015; 150 kDa,
      p < 0.001) between scleral permeability coefficient and thickness. Also, Pc
      declined significantly with increasing molecular weight (MW, p < 0.001, Kruskal
      Wallis). The area that the macromolecules enriched in the scleral surface was
      thicker for those with larger MW (p < 0.001, Kruskal-Wallis). The maximum MW and
      size for equatorial and posterior superotemporal scleral tissue were 185.01 KDa
      and 180.42 KDa, 9.92 nm and 9.67 nm, respectively. CONCLUSIONS: The permeability
      coefficient of porcine sclera has a significant negative relationship with
      scleral thickness and MW of macromolecules. Larger macromolecules are more likely
      to accumulate in scleral surface. The difference between topographical locations
      may have pharmacokinetic implications when considering transscleral diffusion of
      macromolecules.

PMID- 22998135
TI  - Making sense out of antisense in Huntington's disease.

PMID- 22998134
TI  - Glucocorticoid treatment regimen and health outcomes in adults with congenital
      adrenal hyperplasia.
AB  - BACKGROUND: Adults with congenital adrenal hyperplasia (CAH) are treated with a
      wide variety of glucocorticoid treatment regimens. OBJECTIVE, DESIGN AND METHODS:
      To test whether drug dose and timing of glucocorticoid treatment regimen impacts
      on health outcomes. This was a cross-sectional study of 196 adult CAH patients in
      whom treatment and health outcomes were measured. Glucocorticoid dose was
      converted to prednisolone dose equivalent (PreDEq) using three published
      formulae. Associations between the type of glucocorticoid regimen and PreDEq with
      specific health outcome variables were tested using partial correlation and
      principal components analysis (PCA). RESULTS: Patients on dexamethasone had lower
      androgens and ACTH but greater insulin resistance compared with those receiving
      hydrocortisone or prednisolone. Dexamethasone dose and once daily administration
      were associated with insulin resistance. Partial correlation analysis adjusted
      for age and sex showed PreDEq weakly correlated (r < 0.2) with blood pressure and
      androstenedione. Mutation severity was associated with increased PreDEq (F(3,141)
      = 4.4, P < 0.01). In PCA, 3 PCs were identified that explained 62% of the total
      variance (r(2) ) in observed variables. Regression analysis (age and sex
      adjusted) confirmed that PC2, reflecting disease control (androstenedione, 17
      hydroxypregesterone and testosterone), and PC3, reflecting blood pressure and
      mutations (systolic and diastolic blood pressure and mutation severity), related
      directly to PreDEq (r(2)  = 23%, P < 0.001). CONCLUSIONS: In adults with
      congenital adrenal hyperplasia, dexamethasone use was associated with lower
      androgens but greater insulin resistance, and increasing glucocorticoid dose
      associated with increased blood pressure, poor disease control and mutation
      severity.

PMID- 22998136
TI  - Conference report: IANR V and 9th GCNN Conference with 4th ISCITT Symposium.

PMID- 22998137
TI  - Antioxidant status and energy state of erythrocytes in Alzheimer dementia:
      probing for markers.
AB  - Subject age and brain oxidative stress play pivotal roles in Alzheimer disease
      (AD) pathology. Erythrocytes (red blood cells: RBC) are considered as passive
      "reporter cells" for the oxidative status of the whole organism, not active
      participants in mechanisms of AD pathogenesis and are not well studied in AD. The
      aim of this work is to assess whether the antioxidant status and energy state of
      RBC from elderly people change in AD. We measured levels of key products and
      enzymes of oxidative metabolism in RBC from AD (n = 12) and non-Alzheimer
      dementia (NA, n = 13) patients, as well as in cells from age-matched controls
      (AC, n = 14) and younger adult controls (YC, n = 14). Parameters of the adenylate
      system served to evaluate the energy state of RBC. In both aging and dementia,
      oxidative stress in RBC increased and exhibited elevated concentrations of H2O2
      and organic hydroperoxides, decreased the GSH/GSSG ratio and glutathione-S
      transferase activity. Reductions in the ATP levels, adenine nucleotide pool size
      (AN) and adenylate energy charge accompanied these oxidative disturbances. The
      patterns of changes in these indices between groups strongly correlated with each
      other, Spearman rank correlation coefficients being r(s) = 1.0 or -1.0 (p <
      0.01). Alterations of the RBC parameters of oxidative stress and adenylate
      metabolism were nonspecific and interpreted as age-related abnormalities.
      Decreased glutathione peroxidase activity in RBC may be considered as a new
      peripheral marker for AD.

PMID- 22998138
TI  - Amyotrophic lateral sclerosis treatment with ultramicronized
      palmitoylethanolamide: a case report.
AB  - Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized
      by progressive degeneration of motor neurons which leads to muscular atrophy,
      paralysis and death in 3-5 years from starting symptoms. This disorder is
      accompanied by noteworthy spinal inflammation mediated in particular by microglia
      and mast cells. No effective therapy is available. This report describes the
      effects of administering the anti-inflammatory agent palmitoylethanolamide in a
      case of sporadic amyotrophic lateral sclerosis. Palmitoylethanolamide treatment
      led to an improved clinical picture, as evidenced by electromyographic analysis
      and pulmonary function. Conceivably, the action of palmitoylethanolamide could
      result, in part, from its ability to dampen mast cell and microglia activation.

PMID- 22998139
TI  - Radiation-induced neuroinflammation and radiation somnolence syndrome.
AB  - Cranial irradiation remains a standard treatment for malignant and benign brain
      diseases. Although this procedure helps to lengthen the life expectancy of the
      patient, the appearance of adverse effects related to radiation-induced injury is
      inevitable. Radiation somnolence syndrome (RSS) has been described as a delayed
      effect observed mainly after whole-brain radiotherapy in children. The RSS was
      first linked to demyelination, but more recently it has been proposed that the
      inflammatory response plays a primary role in the aforementioned syndrome. To
      evaluate the feasibility of this hypothesis, we explored previous work about RSS
      and reviewed published research that included measurements of the inflammatory
      response in models of brain exposure to ionizing radiation. Pro-inflammatory
      cytokines such as interleukin-1beta, tumor necrosis factor-alpha, interleukin-6
      and interleukin-18 as well as other inflammatory markers such as cyclooxygenase
      2, prostaglandin E2, glial fibrillary acid protein, intercellular adhesion
      molecule-1 and nuclear factor-kappaB appear to be involved in the brain's
      response to radiation. However, certain publications have described the
      somnogenic effects of these cytokines and inflammatory markers. Although the
      radiation response is a complex phenomenon that involves several molecular and
      cellular processes, we propose that inflammation may be closely related to the
      adverse effects of brain irradiation and therefore to the etiology of RSS.

PMID- 22998140
TI  - Outcome-dependent global similarity analysis of imbalanced core signaling
      pathways in ischemic mouse hippocampus.
AB  - Analysis of the diverse interactions of multiple signaling pathways is an
      emerging challenge in the era of networking pharmacology. To reveal imbalanced
      signaling pathways and pharmacological mechanisms involved in ischemic process,
      we designed systemic experiments from top-down to bottom-up for investigating the
      variations of multiple pathways in mouse hippocampal cells. A total of 711 focal
      cerebral ischemia-reperfused animals (504 mice and 207 rats), induced by
      occlusion of the middle cerebral artery, were obtained to conduct 4 experiments.
      The mice were used to analyze the pharmacological effects of four single
      compounds, baicalin (BA), jasminoidin (JA), ursodeoxycholic acid (UA) and concha
      margaritifera (CM) and two combination therapies (BA+JA, and JA+UA). Moreover,
      the mouse models were also used for microarray and western blotting test. The rat
      models were used for infarction volume test, magnetic resonance imaging (MRI)
      test and neurological score analysis to validate the pharmacological effects in
      another species. The results of western blotting confirmed that the expression of
      the key proteins involved in the ischemiaactivated Wnt and nuclear factor kappaB
      (NF-kappaB) pathway was markedly altered. In addition, based on the screened gene
      expression profiles of ischemia hippocampus, a variety of altered genes
      contributed to the 9 stroke-related pathways based on literature review [Wnt,
      extracellular signal-regulated kinase (ERK), janus kinase (JAK), mitogen
      activated protein kinase (MAPK), gonadotropin-releasing hormone (GnRH),
      calcium/calmodulin-dependent protein kinase (CaMK), vascular endothelial growth
      factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor
      (PDGF)] in different groups. Thus, we believed that the 9 signaling pathways were
      significantly imbalanced in different groups. However, analysis of overlapping
      genes was insufficient to reveal the expression profiles of imbalanced pathways
      between or within various conditions treated with different compounds or compound
      mixtures. Therefore, global similarity index (GSI) is introduced to quantify the
      genotypic outcomes of gene expression profiles. Independent experiments in mice
      on the effects of infarction volume, neurologic deficit score and the results of
      MRI in rats showed that GSI was suitable for the spectral measurement of
      imbalance in those 9 biochemical pathways with a predictive accuracy of 81.0% as
      assessed by leave-one-out cross-validation.

PMID- 22998141
TI  - Analogues of the epoxy resin monomer diglycidyl ether of bisphenol F: effects on
      contact allergenic potency and cytotoxicity.
AB  - Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used
      as components in epoxy resin thermosetting products. They are known to cause
      occupational and nonoccupational allergic contact dermatitis. The aim of this
      study is to investigate analogues of DGEBF with regard to contact allergy and
      cytotoxicity. A comprehensive knowledge of the structural features that
      contribute to the allergenic and cytotoxic effects of DGEBF will guide the
      development of future novel epoxy resin systems with reduced health hazards for
      those coming into contact with them. It was found that the allergenic effects of
      DGEBF were dependent on its terminal epoxide groups. In contrast, it was found
      that the cytotoxicity in monolayer cell culture was dependent not only on the
      presence of epoxide groups but also on other structural features.

PMID- 22998142
TI  - Body image and depressive symptoms in 13-year-old adolescents.
AB  - AIMS: To evaluate the prevalence of body dissatisfaction and the association with
      depressive symptoms in 13-year-old adolescents, according to gender, and also to
      analyse the possible modifying effect of body mass index on this association.
      METHODS: We evaluated 1868 adolescents as part of a population-based study in an
      urban community in Porto, Portugal. Using the Figure Rating Scale, participants
      choose their perceived and their desired figures; body dissatisfaction was
      measured by the difference between these values. The Beck Disorder Inventory II
      was used to measure depressive symptoms. Weight and height were measured by
      trained interviewers. To quantify the association between depressive symptoms and
      body dissatisfaction, regression parameters and 95% confidence intervals (CIs)
      were obtained by linear regression and bootstrapping. RESULTS: Among females,
      15.8% desired a bigger figure and 41.4% desired a thinner figure. Among males,
      this occurred for 34.1% and 33.5%, respectively. After adjustment, we found that
      body dissatisfaction was associated with increased depressive symptoms, in both
      genders, especially in those participants who wish to be thinner and in those
      presenting higher discrepancy between figures (B = 6.5, 95% CI 4.1;9.3 for
      females, B = 3.3, 95% CI 1.3;6.8 for males). The association between body
      dissatisfaction and depressive symptoms was stronger among non-overweight (for
      participants who wish to be thinner: B = 5.18 95% CI 3.56; 6.95 vs. B = 3.49, 95%
      CI 1.70; 5.29 among females and B = 2.47, 95% CI 0.73; 4.76 vs. B = 1.60, 95% CI
      0.34; 2.88 among males). CONCLUSIONS: The direct association between the wish to
      be thinner and depressive symptoms was stronger among the non-overweight youth.

PMID- 22998143
TI  - Self-assembly of a [2]pseudorota[3]catenane in water.
AB  - A donor-acceptor [3]catenane incorporating two cyclobis(paraquat-p-phenylene)
      rings linked together by a dinaphtho[50]crown-14 macrocycle possesses a pi
      electron-deficient pocket. Contrary to expectation, negligible binding of a
      hexaethylene glycol chain interrupted in its midriff by a pi-electron-rich 1,5
      dioxynaphthalene unit was observed in acetonitrile. However, a fortuitous solid
      state superstructure of the expected 1:1 complex revealed its inability to
      embrace any stabilizing [C-H...O] interactions between the clearly unwelcome
      guest and the host reluctantly accommodating it. By contrast, in aqueous
      solution, the 1:1 complex becomes very stable thanks to the intervention of
      hydrophobic bonding.

PMID- 22998144
TI  - YAG laser treatment causes rapid degeneration and regeneration of collagen fibres
      in pig skin and facilitates fibroblast growth.
AB  - The non-ablative laser therapies have been speculated to cause microinjury in the
      dermal collagen fibres and increase collagen synthesis in the fibroblasts,
      leading to remodelling of the extracellular matrix. This study investigated the
      effects of neodymium YAG laser treatment on pig skin, especially focusing on its
      extracellular matrix molecules. The dorsal areas of a minipig were subjected to
      laser treatment, and samples were obtained by punch biopsies, and histological,
      immunohistochemical, and biochemical analyses were performed. The laser treatment
      caused degeneration of collagen fibres and fibrils, which were reconstituted
      within 24 hours, whereas there was no inflammation and no apparent damage on
      elastic fibres. Small blood vessels disappeared by the laser treatment, which re
      appeared in 3 days. Biochemically, the amounts of collagen decreased up to day 3
      after the treatment and then increased at day 7. When fibroblasts in dermal
      tissue at day 28 were counted, more fibroblasts in the treated tissue were
      observed than non-treated control. These results suggest that, although the laser
      treatment transiently degenerates collagen fibres and fibrils, it restores and
      increases them, mainly by an increase in dermal fibroblasts, assuring its minimal
      complication of skin.

PMID- 22998145
TI  - Evaluation of muscle hyperactivity of the grimacing muscles by unilateral tight
      eyelid closure and stapedius muscle tone.
AB  - Muscle hyperactivity of grimacing muscles, including the orbicularis oculi and
      corrugator supercilii muscles that cause crow's feet and a glabellar frown line
      with ageing, cannot be accurately evaluated by surface observation. In 71
      subjects, this study investigated the extent to which grimacing muscles are
      innervated by the bilateral motor cortices, whether the corticofacial projection
      to the grimacing muscles affects the facially innervated stapedius muscle tone by
      measuring static compliance of the tympanic membrane, and whether unilateral
      tight eyelid closure with contraction of the grimacing muscles changes static
      compliance. Unilateral tight eyelid closure and its subsequent change in the
      contralateral vertical medial eyebrow position revealed that motor neurons of the
      orbicularis oculi and corrugator supercilii muscles were innervated by the
      bilateral motor cortices with weak-to-strong contralateral dominance. The
      orbicularis oculi, corrugator supercilii, and stapedius muscles innervated by the
      bilateral motor cortices had increased muscle hyperactivity, which lowered the
      vertical medial eyebrow position and decreased the static compliance of the
      tympanic membrane more than those innervated by the unilateral motor cortex.
      Unilateral enhanced tight eyelid closure with contraction of the grimacing
      muscles in certain subjects ipsilaterally decreased the static compliance with
      increased contraction of the stapedius muscle, which probably occurs to
      immobilise the tympanic membrane and protect the inner ear from loud sound.
      Evaluation of unilateral tight eyelid closure and the subsequent change in the
      contralateral vertical medial eyebrow position as well as a measurement of the
      static compliance for the stapedius muscle tone has revealed muscle hyperactivity
      of grimacing muscles.

PMID- 22998146
TI  - Clinical and genetic analysis of microtia in Japan.
AB  - Microtia is thought to have a multifactorial inheritance, but several
      investigators disagree. Here we report our survey of the hereditary factors and
      possible causes. We conducted a questionnaire survey of 428 patients with
      microtia who were being treated at two hospitals from September 2006 to September
      2008. We recorded their age, sex, affected side, duration of gestation, birth
      weight, age of parents at patients' birth, accompanying malformations, number of
      siblings, familial occurrence, smoking habit of parents, and medication/disorders
      of mother during pregnancy, and analysed the results. There were preponderances
      of male (61%), unilateral (90%) and right-sided disease (59%). Other than the
      first and second branchial arch syndrome, microtia is often accompanied by other
      congenital deformities, in particular congenital heart disease; cleft lip, or
      palate, or both; vertebral defects; and anomalies of extremities. The occurrence
      in first-degree relatives was 2%. Most maternal disorders and medication taken
      during pregnancy were common and there was no clear link. Statistically, there
      was a tendency to low birth weight and high maternal age, but it is not possible
      to identify these as a specific cause of microtia. Multifactorial inheritance is
      unlikely to be the cause of microtia as there was only one finding in agreement
      with its widely accepted characteristics. However, we cannot completely discount
      it as there were too few cases in some groups to make a judgement.

PMID- 22998147
TI  - Salvage for pectoralis major myocutaneous flap failure in head and neck
      reconstruction by microvascular flap.
AB  - The pectoralis major myocutaneous pedicled flap (PMMPF) - the "workhorse" for
      head and neck reconstruction - is associated with a high incidence of
      complications in certain cases. This study presents free tissue transfer as an
      alternative salvage technique after PMMPF failure in head and neck
      reconstruction. It includes seven consecutive patients who underwent free tissue
      salvage after PMMPF failure in head and neck reconstruction from January 2008 to
      September 2010 at Kaohsiung Medical University Hospital, Taiwan. Four vertical
      rectus abdominis myocutaneous (VRAM) flaps were applied for tongue and mouth
      floor defects, while three anterolateral thigh (ALT) flaps were used for mouth
      floor, buccal, and cheek defects. All flaps survived uneventfully, and normal
      oral feeding was achieved without major complications. Free tissue transfer has
      several advantages and can be successfully employed in head and neck
      reconstruction, and it is also a reliable salvage procedure after PMMPF failure
      in such cases.

PMID- 22998148
TI  - Differential diagnosis and management of giant fibroadenoma: comparing excision
      with reduction mammoplasty incision and excision with inframammary incision.
AB  - Giant fibroadenoma (GFA) may present with breast asymmetry and can be excised
      with an inframammary incision (IFI) or reduction mammoplasty incision (RMI). This
      study investigated the clinical presentation and compared excision with the IFI
      and RMI. All patients with benign breast tumours greater than 5 cm underwent core
      needle biopsy and a histopathological diagnosis. All confirmed GFA had their
      clinical details documented and randomised into two groups for excision with an
      IFI or RMI. Twenty-two patients were studied. The age range was 12-46 years, mean
      21.18 +/- 2.22 years. The patients were divided into two groups: a juvenile group
      (n = 16) (73%) aged 12-18 years, mean age 14.06 +/- 0.42 years, and a
      perimenopausal group (n = 5) aged 28-46 years. The juvenile group showed cyclic
      increases in breast size monthly with menstruation while the perimenopausal
      showed an initial slow growth of 6-24 months followed by a rapid growth. Fifteen
      patients (68%) had excision biopsy with IMI and seven patients with RMI. Seven of
      the patients treated with IFI had minimal preoperative asymmetry and satisfactory
      aesthetic outcome. Among the patients with severe preoperative asymmetry treated
      with IFI (n = 8) and RMI (n = 7), those treated with IFI had persistent
      postoperative skin redundancy and asymmetry, which was not found in those treated
      with RMI. In conclusion, for patients with significant asymmetry, excision with
      the IFI was associated with persistent asymmetry while excision with RMI was
      associated with restoration of symmetry.

PMID- 22998149
TI  - Replantation or revascularisation injuries in children: incidence, epidemiology,
      and outcome.
AB  - We studied the epidemiology, incidence, and outcome among children and
      adolescents admitted for possible replantation or revascularisation of an injured
      upper extremity during the period 1998-2008. Twenty-nine patients with 38 finger
      injuries were admitted. Eight of the 29 had a severe amputation injury. The
      annual rate of all amputations in the referral area of 300,000 children was
      0.42/100,000 children/year and total amputation injuries 0.18/100,000
      children/year. Most injuries occurred in patients aged 12-15 years. The survival
      after total amputations was 6/14 and after subtotal amputations 13/15. Mean total
      active movement after replantation was 84 degrees  (n = 5) and after
      revascularisation 152 degrees  (n = 10). Four patients were re-examined in the
      outpatient department and nine answered a questionnaire. Cold intolerance was
      reported by most of the patients. Patients' satisfaction with outcome of
      treatment was good.

PMID- 22998150
TI  - Influence of a GC base pair on excitation energy transfer in DNA-assembled
      phenanthrene pi-stacks.
AB  - The effect of a GC base pair on the excitation energy transfer in a DNA-based,
      light harvesting assembly of phenanthrene and pyrene chromophores is described.
      After absorption of light at 320 nm by the stacked phenanthrene building blocks,
      the excitation energy is transferred to the pyrene and leads to the formation of
      a phenanthrene-pyrene exciplex. The fluorescence intensity depends on the number
      of light absorbing phenanthrenes, as well as on the type of DNA base pair
      flanking the phenanthrene stack. In comparison to an AT base pair, a GC base pair
      located next to the stacked aromatic residues results in a reduction of
      fluorescence. The degree of quenching is dependent on the length of the
      phenanthrene stack that separates the GC base pair from the exciplex. Overall, a
      large number of stacked phenanthrenes positively affects exciplex fluorescence by
      increasing the quantity of absorbed light and, at the same time, reducing the
      effect of quenching by GC base pairs.

PMID- 22998152
TI  - Interaction of nonionic surfactants and hydrophilic ionic liquids in aqueous
      solutions: can short ionic liquids be more than a solvent?
AB  - The interaction between an ethoxylated nonionic surfactant (C(12-14)EO(8)) and
      three conventional hydrophilic imidazolium-based ionic liquids (bmim-octyl SO(4),
      bmim-methyl SO(4), and bmim-BF(4)) in aqueous solution has been investigated. In
      most of the reported studies where a surfactant is dissolved in an ionic liquid
      aqueous solution, conventional ionic liquids are merely considered to be
      solvents. Consequently, the resulting critical micelle concentration (cmc) is
      considered to be that of the surfactant. However, given that the three ionic
      liquids selected showed the typical shape of a surface-active compound when the
      surface tension was plotted against concentration, the role of these compounds as
      secondary surfactants and consequently the possibility of mixed-micelle formation
      have been investigated. Different series of experiments where a surfactant and an
      ionic liquid were combined in a wide range of mole ratios have been performed and
      treated as typical binary surfactant systems in aqueous solution. It has been
      found for the three surfactant/ionic liquid systems that depending on the
      surfactant mole fraction, alpha(1), attractive or repulsive interactions in mixed
      micelle formation are produced. Therefore, when we select the appropriate
      alpha(1) these systems can be adjusted to a given application, depending on
      whether monomers or micelles are mainly required.

PMID- 22998151
TI  - Developing resources to support the diagnosis and management of Chronic Fatigue
      Syndrome/Myalgic Encephalitis (CFS/ME) in primary care: a qualitative study.
AB  - BACKGROUND: NICE guidelines emphasise the need for a confident, early diagnosis
      of Chronic Fatigue Syndrome/ Myalgic Encephalitis (CFS/ME) in Primary Care with
      management tailored to the needs of the patient. Research suggests that GPs are
      reluctant to make the diagnosis and resources for management are currently
      inadequate. This study aimed to develop resources for practitioners and patients
      to support the diagnosis and management of CFS/ME in primary care. METHODS: Semi
      structured interviews were conducted with patients, carers, GPs, practice nurses
      and CFS/ME specialists in North West England. All interviews were audio recorded,
      transcribed and analysed qualitatively using open explorative thematic coding.
      Two patient involvement groups were consulted at each stage of the development of
      resources to ensure that the resources reflect everyday issues faced by people
      living with CFS/ME. RESULTS: Patients and carers stressed the importance of
      recognising CFS/ME as a legitimate condition, and the need to be believed by
      health care professionals. GPs and practice nurses stated that they do not always
      have the knowledge or skills to diagnose and manage the condition. They expressed
      a preference for an online training package. For patients, information on getting
      the most out of a consultation and the role of carers was thought to be
      important. Patients did not want to be overloaded with information at diagnosis,
      and suggested information should be given in steps. A DVD was suggested, to
      enable information sharing with carers and family, and also for those whose
      symptoms act as a barrier to reading. CONCLUSION: Rather than use a top-down
      approach to the development of training for health care practitioners and
      information for patients and carers, we have used data from key stakeholders to
      develop a patient DVD, patient leaflets to guide symptom management and a modular
      e-learning resource which should equip GPs to diagnose and manage CFS/ME
      effectively, meet NICE guidelines and give patients acceptable, evidence-based
      information.

PMID- 22998153
TI  - Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9
      GP), a glycoPEGylated recombinant factor IX.
AB  - BACKGROUND: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX
      (rFIX) molecule with a prolonged half-life. OBJECTIVES: To provide information on
      potential dose regimens for N9-GP for phase 3 pivotal and surgery trials.
      METHODS: A population pharmacokinetic model was developed from single-dose data
      derived from the first human-dose trial with N9-GP in hemophilia B patients, and
      was used to extrapolate to steady-state conditions for different N9-GP dose
      regimens for prophylaxis. The model was also used to compare prophylaxis using N9
      GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40
      IU kg(-1) every third day). Plasma activity following dosing with N9-GP, rFIX and
      pdFIX for surgery and on-demand treatment of bleeds was also simulated. RESULTS:
      A linear two-compartmental model best described the pharmacokinetic profiles of
      N9-GP, rFIX and pdFIX. A prophylactic regimen of 10 U kg(-1) N9-GP once weekly
      predicted mean peak and trough levels of 18 and 4.2 U dL(-1) , while 40 U kg(-1)
      once weekly predicted values of 72 and 17 U dL(-1) , respectively. Standard
      prophylactic regimens with rFIX and pdFIX predicted mean peak and trough levels
      of 34 and 3.9 IU dL(-1) for rFIX, and mean values of 43 and 2.1 IU dL(-1) for
      pdFIX. Additional simulations predicted significantly reduced dosing frequency
      and factor concentrate consumption for N9-GP vs. rFIX and pdFIX for surgery and
      the treatment of bleeds. CONCLUSIONS: N9-GP may allow prophylaxis, surgical
      dosing regimens and on-demand treatment of bleeding episodes with less frequent
      injections and lower factor concentrate consumption; this possibility is being
      investigated in prospective clinical trials.

PMID- 22998154
TI  - Modification of alkanethiolate monolayers by O(3P) atomic oxygen: effect of chain
      length and surface temperature.
AB  - We have conducted a comprehensive study of ground-state O((3)P) atomic oxygen
      reactions with 1-hexadecanethiolate (CH3(CH2)15SH) and 1-undecanethiolate
      (CH3(CH2)10SH) self-assembled monolayers adsorbed onto Au/mica substrates, using
      X-ray photoelectron spectroscopy, infrared reflection absorption spectroscopy,
      ellipsometry, and contact angle measurements. In general, the reactions are not
      limited to the terminal methyl groups. Apparently, the incident O((3)P)
      (translational energy per atom of 0.11 kJ mol(-1)) can penetrate below the
      surface of the monolayer. The ability of the atoms to penetrate, and thus the
      reaction rate of the backbone -CH2-, is dependent upon both the temperature and
      the chain length, with the longer chain having a large difference between the
      rate at room temperature and 150 K. In particular, the long-chain SAM exhibits
      clearly reduced reactivity with respect to the incident beam of atomic oxygen
      when the film is cooled to 150 K as compared to room temperature. This is a
      notable finding and demonstrates the crucial importance that structural order and
      dynamical fluctuations, both of which depend on chain length and substrate
      temperature, have in determining the surface passivation and protection
      characteristics of SAM overlayers with respect to attack by energetic reagents.

PMID- 22998155
TI  - Food insecurity, processes of care, and self-reported medication underuse in
      patients with type 2 diabetes: results from the California Health Interview
      Survey.
AB  - OBJECTIVE: To assess the independent association of food insecurity with
      processes of care and delays in filling prescriptions. DATA SOURCE: 2007
      California Health Interview Survey. STUDY DESIGN: Associations of food insecurity
      with processes of care and delays in filling prescriptions were examined using
      multivariable logistic regression analyses adjusted for sociodemographic
      characteristics, barriers to accessing care, and health status. DATA EXTRACTION:
      Data were analyzed from adults currently receiving treatment for type 2 diabetes
      and who had seen a doctor in the prior 12 months (N = 3,401). PRINCIPAL FINDINGS:
      For diabetes patients currently receiving medical care, food insecurity was not
      associated with lower rates of performance of recommended processes of care, but
      it was associated with delays in filling prescriptions (aOR = 2.15, 95 percent CI
      1.25, 3.71). CONCLUSIONS: Food insecurity may increase delays in filling
      prescriptions in daily life, even though the performance of recommended processes
      of care in the clinic is not diminished.

PMID- 22998156
TI  - Molecular mechanisms involved in antibody-dependent enhancement of dengue virus
      infection in humans.
AB  - Dengue is the most common arthropod-borne viral infection in humans with ~50
      million cases annually worldwide. In recent decades, a steady increase in the
      number of severe dengue cases has been seen. Severe dengue disease is most often
      observed in individuals that have pre-existing immunity against heterotypic
      dengue subtypes and in infants with low levels of maternal dengue antibodies. The
      generally accepted hypothesis explaining the immunopathogenesis of severe dengue
      is called antibody-dependent enhancement of dengue infection. Here, circulating
      antibodies bind to the newly infecting virus but do not neutralize infection.
      Rather, these antibodies increase the infected cell mass and virus production.
      Additionally, antiviral responses are diminished allowing massive virus particle
      production early in infection. The large infected cell mass and the high viral
      load are prelude for severe disease development. In this review, we discuss what
      is known about the trafficking of dengue virus in its human host cells, and the
      signalling pathways activated after virus detection, both in the absence and
      presence of antibodies against the virus. This review summarizes work that aims
      to better understand the complex immunopathogenesis of severe dengue disease.

PMID- 22998157
TI  - Functional diversity of Teleost arylalkylamine N-acetyltransferase-2: is the
      timezyme evolution driven by habitat temperature?
AB  - Arylalkylamine N-acetyltransferase-2 (AANAT2) is the enzyme responsible for the
      rhythmic production of the time-keeping hormone melatonin. It plays a crucial
      role in the synchronization of biological functions with changes in the
      environment. Annual and daily fluctuations in light are known to be key
      environmental factors involved in such synchronization. Previous studies have
      demonstrated that AANAT2 activity is also markedly influenced by temperature but
      the mechanisms through which it impacts the enzyme activity need to be further
      deciphered. We investigated AANAT2 primary to tertiary structures (3D models) and
      kinetics in relation to temperature for a variety of Teleost species from
      tropical to Arctic environments. The results extend our knowledge on the
      catalytic mechanisms of AANAT enzymes and bring strong support to the idea that
      AANAT2 diversification was limited by stabilizing selection conferring to the
      enzyme well conserved secondary and tertiary structures. Only a few changes in
      amino acids appeared sufficient to induce different enzyme activity patterns. It
      is concluded that AANAT2 evolution is mainly driven by phylogenetic relationships
      although catalytic properties (enzyme turnover and substrate affinity) are also
      under the influence of the respective species normal habitat temperature.

PMID- 22998158
TI  - Autonomic symptoms and dopaminergic treatment in de novo Parkinson's disease.
AB  - OBJECTIVES: Autonomic symptoms are present in early stages of Parkinson's disease
      (PD), but evidence on how they are influenced by dopaminergic treatment remains
      unclear. The aim of this study was to investigate the impact of dopaminergic
      treatment on autonomic symptoms in early PD in a population-based cohort.
      METHODS: A total of 171 drug-naive patients with PD were investigated at
      diagnosis and 12 months later. Orthostatic blood pressure was measured, and
      autonomic symptoms were assessed by a preliminary version of the Movement
      Disorders Society-sponsored new version of the Unified Parkinson's Disease Rating
      Scale (range 0-4). RESULTS: In the 82% using dopaminergic treatment after 1 year,
      constipation and orthostatic blood pressure drop increased. There was a tendency
      towards increased orthostatic dizziness and urinary dysfunction. Dysphagia scores
      were reduced, and this was associated with higher levodopa-equivalent daily dose.
      CONCLUSIONS: Dopaminergic treatment during the first year after initiation seems
      to have only a minor impact on autonomic symptoms in early PD. It may increase
      constipation and orthostatic dizziness, while dysphagia can improve. Autonomic
      symptoms remained mild after 1 year of dopaminergic treatment.

PMID- 22998159
TI  - Clear cell hidradenocarcinoma with helpful immunohistochemistry: a case report.

PMID- 22998160
TI  - Transfusion of banked red blood cells and the effects on hemorrheology and
      microvascular hemodynamics in anemic hematology outpatients.
AB  - BACKGROUND: The aim of this study was to investigate the effects of red blood
      cell (RBC) transfusion on the hemorrheologic properties and microcirculatory
      hemodynamics in anemic hematology outpatients receiving 2 to 4 RBC units of
      either "fresh" (leukoreduced storage for less than 1 week) or "aged"
      (leukoreduced storage for 3-4 weeks) RBCs. STUDY DESIGN AND METHODS: Measurements
      were performed before and 30 minutes after RBC transfusion in hematology
      outpatients. Leukoreduced RBC suspensions were stored in saline-adenine-glucose
      mannitol (SAGM) additive solution. Whole blood viscosity was measured using
      Couette low-shear viscometry, RBC deformability and aggregability were measured
      using laser-assisted optical rotational cell analysis, and microcirculatory
      density and perfusion were assessed using sidestream dark field imaging. RESULTS:
      One group of patients (n = 10) received a median (interquartile range) of 3 (2-3)
      RBC bags that were stored for 7 (5-7) days (fresh) and the other group of
      patients (n = 10) received 3 (3-3) RBC bags that were stored for 23 (22-28) days
      (aged). After transfusion of fresh versus aged RBCs, hematocrit increased to 32
      +/- 3% versus 31 +/- 2% (p < 0.363), whole blood viscosity increased to 4.2 +/-
      0.4 Pa/sec versus 4.2 +/- 0.6 Pa/sec (p < 0.912), RBC deformability index
      remained unaffected, RBC aggregability index increased to 55 +/- 10 versus 55 +/-
      13 (p = 0.967), microcirculatory flow remained unaffected, and microcirculatory
      density increased to 19.3 +/- 2.5 mm/mm(2) versus 18.7 +/- 1.9 mm/mm(2) (p =
      0.595), respectively. CONCLUSION: Storing leukoreduced SAGM-suspended RBCs for 3
      to 4 weeks did not affect their ability to improve hemorrheologic properties and
      microcirculatory hemodynamics in our small group of anemic hematology
      outpatients. Larger studies are needed to confirm this finding.

PMID- 22998161
TI  - Diminazene diaceturate for treatment of chronic Cytauxzoon felis parasitemia in
      naturally infected cats.
AB  - BACKGROUND: Cytauxzoon felis is a hemoprotozoal parasite that causes substantial
      morbidity and mortality during the acute phase of infection in cats. However,
      cats that survive the acute illness remain persistently infected and may serve as
      a reservoir for the tick-transmitted pathogen. OBJECTIVE: We investigated the
      ability of the antiprotozoal compound diminazene diaceturate to eliminate the
      pathogen from naturally infected C. felis carriers. ANIMALS: Seven healthy,
      chronically infected domestic cats housed in a research setting. METHODS:
      Prospective clinical trial. Cats were treated in a masked fashion with diminazene
      diaceturate (3 mg/kg) or placebo IM in a series of 2 injections 7 days apart.
      Clearance of the organism was assessed by light microscopy and real-time
      polymerase chain reaction (PCR) at 0, 3, 6, and 10 weeks. In addition, cats were
      monitored for behavioral changes or for changes on physical examination, CBC,
      plasma biochemical profile, and urinalysis periodically. Cats that remained
      parasitemic at the end of 10 weeks were switched to the alternative treatment and
      similarly monitored for an additional 10 weeks. RESULTS: Adverse events
      associated with treatment were limited to self-resolving hypersalivation and
      injection site soreness; the former was ameliorated by premedication with
      atropine. Parasite burden, as assayed by both light microscopy and real-time PCR,
      was similar between diminazene- and placebo-treated cats. CONCLUSIONS AND
      CLINICAL RELEVANCE: Diminazene diaceturate was unable to eliminate the pathogen
      or decrease parasite burden in healthy, chronically infected cats.

PMID- 22998162
TI  - Self-esteem in 6- to 16-year-olds with monosymptomatic nocturnal enuresis.
AB  - AIM: Childhood nocturnal enuresis (NE) and incontinence has been shown to be
      associated with increased behavioural problems and reduced self-esteem (SE) in
      Western populations. The impact on Asian children, however, is not known. This
      study investigates the relationship between SE and monosymptomatic NE in
      Malaysian children aged 6 to 16 years. METHOD: Children with wetting frequency of
      at least 4 out of 14 nights were recruited with controls matched for age, gender
      and race. SE scores were obtained using the 'I Think I Am' questionnaire for five
      domains: body image, talents and skills, psychological well-being, relationship
      with family and relationship with others. RESULTS: A total of 126 children were
      recruited; 22 enuretics aged 6-9 years and their matched controls (Group1) and 41
      enuretics aged 10-16 years and their matched controls (Group 2). SE scores were
      similar between the enuretic and controls in Group 1, whereas in Group 2,
      enuretics had significantly lower scores (P < 0.05) in 'body image',
      'relationship with others' and total SE scores. This difference was more
      pronounced among girls, adolescents and those who wet more than 10/14 nights.
      CONCLUSION: The SE of Malaysian children with monosymptomatic NE aged 10 years
      and above is significantly lower than their peers. This effect is seen
      particularly among girls, adolescents and those with frequent wetting. In the
      light of these findings, the 'wait and see' approach by the Malaysian medical
      profession is no longer appropriate. Treatment should begin before the age of 10
      years.

PMID- 22998163
TI  - Molecular design, synthesis, and evaluation of novel potent apoptosis inhibitors
      inspired from bongkrekic acid.
AB  - Bongkrekic acid (BKA) is an inhibitor of adenine nucleotide translocase (ANT).
      Since inhibition of ANT is connected to the inhibition of cytochrome c release
      from mitochondria, which then results in the suppression of apoptosis, it has
      been used as a tool for the mechanistic investigation of apoptosis. BKA consists
      of a long carbon chain with two asymmetric centers, a nonconjugated olefin, two
      conjugated dienes, three methyl groups, a methoxyl group, and three carboxylic
      acids. This complicated chemical structure has caused difficulties in synthesis,
      supply, and biochemical mechanistic investigations. In this study, we designed
      and synthesized more simple tricarboxylic acids that were inspired by the
      molecular structure of BKA. Their cytotoxicity and apoptosis-preventing activity
      in HeLa cells and the effect on the mitochondrial inner membrane potential
      (DeltaPsim) in HL-60 cells were then evaluated. All tested tricarboxylic acid
      derivatives including BKA showed little toxicity against HeLa cells. BKA and two
      of the synthesized derivatives significantly suppressed staurosporine (STS)
      induced reductions in cell viability. Furthermore, STS-induced DeltaPsim collapse
      was significantly restored by pretreatment with BKA and a tricarboxylic acid
      derivative. Other derivatives, in which one of three carboxylic acids was
      esterified, exhibited potent toxicity, especially a derivative bearing a carbon
      chain of the same length as that of BKA. In conclusion, we have developed a new
      lead compound as an apoptosis inhibitor bearing three carboxylic acids connected
      with the proper length of a long carbon chain.

PMID- 22998164
TI  - Latest advances in computational genotoxicity prediction.
AB  - INTRODUCTION: Computational approaches for genotoxicity prediction have existed
      for over two decades. Numerous methodologies have been utilized and the results
      of various evaluations have published. AREAS COVERED: In silico methods are
      considered mature enough to be part of draft FDA regulatory guidelines for the
      assessment of genotoxic impurities. However, aspects of how best to use
      predictive systems remain unresolved: i) methodologies to measure how similar two
      compounds need to be in order to assume they have the same biological outcome;
      and ii) defining whether a compound is close enough to the model training set
      such that a model prediction can be considered reliable. EXPERT OPINION: In
      silico prediction of genotoxicity is a fundamental part of screening strategies
      for the assessment genotoxic impurities in drug products. However, the concept of
      using chemical similarity to infer mutagenic potential from one of known activity
      to another whose activity is unknown remains a scientific challenge. Similarly,
      defining when an in silico model prediction can be considered to be reliable is
      also difficult. Reaction mechanisms and the functional group building blocks of
      chemistry are pretty much constant, and so when data-gaps appear, it tends to be
      for compounds that have been regularly used but rarely tested.

PMID- 22998165
TI  - 'Training' friends and family to provide positive social support in diabetes self
      management: experience of ethnically diverse patients.

PMID- 22998166
TI  - Prime time for minor subunits of the type II secretion and type IV pilus systems.
AB  - The type II secretion system (T2SS) exports folded proteins from the periplasms
      of Gram-negative bacteria. The type IV pilus system (T4PS) is a multifunctional
      machine used for adherence, motility and DNA transfer in bacteria and archaea.
      Partial sequence identity between the two systems suggests that they are related
      and might function via a similar mechanism, the dynamic assembly and disassembly
      of pseudopilus (T2SS) or pilus (T4PS) filaments. The major subunit in each system
      is thought to form the bulk of the (pseudo)pilus, while minor (low-abundance)
      subunits have proposed roles in assembly initiation, antagonism of disassembly,
      or modulation of (pseudo)pilus functional properties. In this issue, Cisneros et
      al. () extend their previous finding that pseudopilus assembly is primed by the
      minor pseudopilins, showing that the same proteins can initiate assembly of
      Escherichia coli T4P. Similarly, they show that the E. coli minor pilins prime
      the polymerization of T2S pseudopili, although unlike genuine pseudopili, the
      chimeric filaments did not support secretion. This work reinforces the notion of
      a common assembly mechanism for the T2S and T4P systems.

PMID- 22998167
TI  - Cone pathway function in relation to asymmetric carotid artery stenosis:
      correlation to blood pressure - author's reply.

PMID- 22998168
TI  - In situ SVVYGLR peptide conjugation into injectable gelatin-poly(ethylene glycol)
      tyramine hydrogel via enzyme-mediated reaction for enhancement of endothelial
      cell activity and neo-vascularization.
AB  - Tissue engineering therapies require biocompatible and bioactive biomaterials
      that are capable of encouraging an angiogenic response for effective tissue
      regeneration. In this study, a SVVYGLR peptide, which functions as a potent
      angiogenic factor, was conjugated into injectable gelatin-poly(ethylene glycol)
      tyramine (GPT) hydrogels in situ to enhance endothelial cell activities and neo
      vascularization. SVVYGLRGGY (SV-Y) conjugated GPT (SV-GPT) hydrogels were formed
      in situ via enzyme-mediated reaction using horseradish peroxidase (HRP) and
      hydrogen peroxide (H(2)O(2)). The physico-chemical properties were characterized
      and could be controlled depending on the feed peptide and H(2)O(2) concentration.
      The concentration of conjugated peptide ranged from 0.37 to 0.81 MUmol/mL, and
      the elastic moduli (G') of the hydrogels were 600-4900 Pa. In vitro cell studies
      using human umbilical vein endothelial cells (HUVECs) and in vivo subcutaneous
      injection studies were performed to confirm the effect of the SVVYGLR peptide on
      HUVEC activity and neo-vascularization. Obtained results demonstrated that the in
      situ conjugation of SVVYGLR sequences into phenol residues of GPT hydrogels
      enhanced the activity of HUVECs in vitro and stimulated the formation of new
      blood vessels in the hydrogel matrices in vivo. From the results, we suggest that
      in situ conjugation of SV-Y to GPT hydrogels via the enzymatic reaction may be an
      efficient tool to prepare injectable bioactive hydrogels that can enhance
      endothelial cell activities and promoting angiogenesis for tissue regeneration.

PMID- 22998169
TI  - The care for chronic heart failure by general practitioners. Results from a
      clinical audit in Italy.
AB  - BACKGROUND: In Italian primary care, chronic heart failure (CHF) patients are
      mainly managed by general practitioners (GPs). However, there are few studies
      analysing CHF management challenges in primary care and identifying opportunities
      for improvement. OBJECTIVES: To describe CHF care as implemented by GPs in the
      Veneto Region and to identify opportunities for improvement. METHODS: In 2008,
      using an audit process, 114 Venetian GPs analysed their electronic health
      records, identified CHF patients and collected clinical and care related
      information: prevalence, co-morbidity, caring conditions, diagnostic and
      therapeutic management, and hospitalization. After two training sessions, data on
      pharmacotherapy were analysed again in 2009. RESULTS: The prevalence of CHF was
      1.2% (95% CI: 1.1-1.3%). Diagnostic echocardiography was used in 57% of cases. At
      baseline, the proportions of patients that used specific medication were:
      diuretics 88%; angiotensin converting enzyme (ACE) inhibitors or angiotensin
      receptor blockers (ARB) 77%, beta-blockers 46% and anti-aldosterone agents 32%.
      After two training sessions, the use of ACE inhibitors/ARB and beta-blockers
      increased to 80% and 56%, respectively. Renal failure, chronic obstructive
      pulmonary disease (COPD), diabetes mellitus and dementia were the most prevalent
      concomitant diseases, posing specific management problems. Half of the patients
      were generally visited at home; they were dependent on some kind of care given.
      CONCLUSION: In Veneto a large number of CHF patients are mainly managed by GPs.
      Further improvements are necessary to meet standards of care with regard to
      diagnosis, medication, follow-up and home care. The care situation affected
      hospitalization and the quality of follow-up visits.

PMID- 22998170
TI  - Design of enzyme-mediated controlled release systems based on silica mesoporous
      supports capped with ester-glycol groups.
AB  - An ethylene glycol-capped hybrid material for the controlled release of molecules
      in the presence of esterase enzyme has been prepared. The final organic-inorganic
      hybrid solid S1 was synthesized by a two-step procedure. In the first step, the
      pores of an inorganic MCM-41 support (in the form of nanoparticles) were loaded
      with [Ru(bipy)(3)]Cl(2) complex, and then, in the second step, the pore outlets
      were functionalized with ester glycol moieties that acted as molecular caps. In
      the absence of an enzyme, release of the complex from aqueous suspensions of S1
      at pH 8.0 is inhibited due to the steric hindrance imposed by the bulky ester
      glycol moieties. Upon addition of esterase enzyme, delivery of the ruthenium
      complex was observed due to enzymatic hydrolysis of the ester bond in the
      anchored ester glycol derivative, inducing the release of oligo(ethylene glycol)
      fragments. Hydrolysis of the ester bond results in size reduction of the appended
      group, therefore allowing delivery of the entrapped cargo. The S1 nanoparticles
      were not toxic for cells, as demonstrated by cell viability assays with HeLa and
      MCF-7 cell lines, and were found to be associated with lysosomes, as shown by
      confocal microscopy. However, when S1 nanoparticles were filled with the
      cytotoxic drug camptothecin (S1-CPT), S1-CPT-treated cells undergo cell death as
      a result of S1-CPT cell internalization and subsequent cellular enzyme-mediated
      hydrolysis and aperture of the molecular gate that induced the release of the
      camptothecin cargo. These findings point to a possible therapeutic application of
      these nanoparticles.

PMID- 22998171
TI  - Development of alpha-helical calpain probes by mimicking a natural protein
      protein interaction.
AB  - We have designed a highly specific inhibitor of calpain by mimicking a natural
      protein-protein interaction between calpain and its endogenous inhibitor
      calpastatin. To enable this goal we established a new method of stabilizing an
      alpha-helix in a small peptide by screening 24 commercially available cross
      linkers for successful cysteine alkylation in a model peptide sequence. The
      effects of cross-linking on the alpha-helicity of selected peptides were examined
      by CD and NMR spectroscopy, and revealed structurally rigid cross-linkers to be
      the best at stabilizing alpha-helices. We applied this strategy to the design of
      inhibitors of calpain that are based on calpastatin, an intrinsically unstable
      polypeptide that becomes structured upon binding to the enzyme. A two-turn alpha
      helix that binds proximal to the active site cleft was stabilized, resulting in a
      potent and selective inhibitor for calpain. We further expanded the utility of
      this inhibitor by developing irreversible calpain family activity-based probes
      (ABPs), which retained the specificity of the stabilized helical inhibitor. We
      believe the inhibitor and ABPs will be useful for future investigation of
      calpains, while the cross-linking technique will enable exploration of other
      protein-protein interactions.

PMID- 22998173
TI  - What determines the income gap between French male and female GPs - the role of
      medical practices.
AB  - BACKGROUND: In many OECD countries, the gender differences in physicians' pay
      favour male doctors. Due to the feminisation of the doctor profession, it is
      essential to measure this income gap in the French context of Fee-for-service
      payment (FFS) and then to precisely identify its determinants. The objective of
      this study is to measure and analyse the 2008 income gap between males and
      females general practitioners (GPs). This paper focuses on the role of gender
      medical practices differentials among GPs working in private practice in the
      southwest region of France. METHODS: Using data from 339 private-practice GPs, we
      measured an average gender income gap of approximately 26% in favour of men.
      Using the decomposition method, we examined the factors that could explain gender
      disparities in income. RESULTS: The analysis showed that 73% of the income gap
      can be explained by the average differences in doctors' characteristics; for
      example, 61% of the gender income gap is explained by the gender differences in
      workload, i.e., number of consultations and visits, which is on average
      significantly lower for female GPs than for male GPs. Furthermore, the
      decomposition method allowed us to highlight the differences in the marginal
      returns of doctors' characteristics and variables contributing to income, such as
      GP workload; we found that female GPs have a higher marginal return in terms of
      earnings when performing an additional medical service. CONCLUSIONS: The findings
      of this study help to understand the determinants of the income gap between male
      and female GPs. Even though workload is clearly an essential determinant of
      income, FFS does not reduce the gender income gap, and there is an imperfect
      relationship between the provision of medical services and income. In the context
      of feminisation, it appears that female GPs receive a lower income but attain
      higher marginal returns when performing an additional consultation.

PMID- 22998174
TI  - Analysis of the insulin-like growth factor 1 receptor gene in children born small
      for gestational age: in vitro characterization of a novel mutation (p.Arg511Trp).
AB  - BACKGROUND: Insulin-like growth factor 1 insensitivity caused by IGF1R mutations
      has been previously identified as one of the causes of growth impairment in
      children born small for gestational age (SGA). OBJECTIVE: To analyse the IGF1R in
      children born SGA. SUBJECTS: From an initial cohort of 54 sequential children
      born SGA, without catch-up growth, 25 children were selected for this IGF1R study
      due to the presence of serum IGF-1 values above the mean for their age and sex.
      METHODS: The proximal IGF1R promoter region, the entire coding region and the
      exon-intron boundaries were directly sequenced, and multiplex ligation-dependent
      probe amplification analysis was performed. Fibroblast cultures were developed
      from one patient with a mutation for the in vitro characterization of IGF-1
      insensitivity. RESULTS: The copy number variation analysis did not identify
      deletions involving the IGF1R gene. We identified two children carrying
      heterozygous nucleotide substitutions in IGF1R: c.16G>A/p.Gly6Arg and
      c.1531C>T/p.Arg511Trp. The first variant (p.Gly6Arg) was identified in control
      subjects (0.3%) and in a relative with normal growth; thus, it was considered to
      be a rare benign allelic variation. The second variant (p.Arg511Trp) was not
      found in 306 alleles from control subjects, and it segregated with the growth
      impairment phenotype in the patient's family. Fibroblasts obtained from this
      patient had a significantly reduced proliferative response and AKT
      phosphorylation after IGF-1 stimulation compared with control fibroblasts.
      CONCLUSION: The identification of an inactivating IGF1R mutation in the present
      cohort should encourage further studies of larger series to establish the precise
      frequency of this molecular defect in children with growth impairment of a
      prenatal onset.

PMID- 22998180
TI  - SiC-CNT composite prepared by electrophoretic codeposition and the polymer
      infiltration and pyrolysis process.
AB  - The paper reports on the successful anodic codeposition of submicrometer SiC
      powder and multiwalled carbon nanotubes from aqueous suspensions to form SiC-CNT
      composites. On the basis of the comprehensive analysis of the aqueous suspensions
      with different pHs, solids contents, and CNT contents, optimal conditions for
      deposition were determined. Besides having the necessary high absolute value of
      the zeta-potential, the suspensions that resulted in firm deposits were
      characterized by limited conductivity (<1 mS/cm). Lowering of suspension
      conductivity was achieved either by dilution of the suspension or by dialysis of
      the as-received CNT suspension with high intrinsic conductivity. Selected SiC-CNT
      deposits were further densified by use of the polymer infiltration and pyrolysis
      process.

PMID- 22998175
TI  - Stereoselective radical amination of electron-deficient C(sp3)-H bonds by Co(II)
      based metalloradical catalysis: direct synthesis of alpha-amino acid derivatives
      via alpha-C-H amination.
AB  - The cobalt(II) complex of 3,5-Di(t)Bu-IbuPhyrin, [Co(P1)], is an effective
      catalyst for intramolecular amination of electron-deficient C-H bonds, including
      those adjacent to electron-withdrawing CO(2)R, C(O)NR(2), C(O)R, and CN groups,
      in excellent yields with high regio- and stereoselectivity. The [Co(P1)]
      catalyzed amination system provides a direct method for the synthesis of alpha
      amino acid derivatives from the corresponding carboxylate precursors.

PMID- 22998181
TI  - In vitro activity of aminosterols against dermatophytes.
AB  - We recently reported that aminosterols are fungicidal due to their disrupting the
      outer membranes of yeasts and that they have a significant in vitro activity
      against various mould species. Yet, their activity against dermatophytes had
      never been tested. This study's objective was to evaluate the in vitro activity
      of squalamine and a synthetic aminosterol derivative (ASD) against various
      dermatophytes. Susceptibility testing of squalamine, ASD, terbinafine, and
      griseofulvin was performed, in triplicate, in accord with the Clinical Laboratory
      and Standards Institute's M38-A2 procedure, using an 80% growth inhibition
      endpoint. The studies included the following dermatophytes: Trichophyton rubrum,
      T. mentagrophytes, T. soudanense, Microsporum canis, M. audouinii, M. persicolor;
      M. cookie and M. gypseum. Squalamine and ASD showed significant in vitro activity
      against these dermatophytes. The minimum inhibitory concentrations (MICs) ranged
      from 4-16 mg/l and from 2-8 mg/l for squalamine and ASD, respectively. These
      findings support further clinical studies of aminosterols activity against
      superficial dermatophyte infections.

PMID- 22998182
TI  - Long-term radical prostatectomy outcomes among participants from the European
      Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam.
AB  - Study Type--Therapy (cohort) Level of Evidence 2b. What's known on the subject?
      and What does the study add? Radical prostatectomy was previously shown to
      improve long-term outcomes among men with clinically-detected prostate cancer.
      Our data suggests that radical prostatectomy is also associated with improved
      outcomes in men with screen-detected prostate cancer. OBJECTIVE: * To examine the
      long-term outcomes of radical prostatectomy (RP) among men diagnosed with
      prostate cancer from the screening and control arms of the Rotterdam section of
      the European Randomized Study of Screening for Prostate Cancer (ERSPC). PATIENTS
      AND METHODS: * Among 42,376 men randomised during the period of the first round
      of the trial (1993-1999), 1151 and 210 in the screening and control arms were
      diagnosed with prostate cancer, respectively. * Of these men, 420 (36.5%) screen
      detected and 54 (25.7%) controls underwent RP with long-term follow-up data
      (median follow-up 9.9 years). * Progression-free (PFS), metastasis-free (MFS) and
      cancer-specific survival (CSS) rates were examined, and multivariable Cox
      proportional hazards models were used to determine whether screen-detected (vs
      control) was associated with RP outcomes after adjusting for standard predictors.
      RESULTS: * RP cases from the screening and control arms had statistically similar
      clinical stage and biopsy Gleason score, although screen-detected cases had
      significantly lower prostate-specific antigen (PSA) levels at diagnosis. * Men
      from the screening arm had a significantly higher PFS (P = 0.003), MFS (P <
      0.001) and CSS (P = 0.048). * In multivariable models adjusting for age, PSA
      level, clinical stage, and biopsy Gleason score, the screening group had a
      significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95%
      confidence interval [CI] 0.23-0.83, P = 0.011) and metastasis (HR 0.18, 95% CI
      0.06-0.59, P = 0.005). * Additionally adjusting for tumour volume and other RP
      pathology features, there was no longer a significant difference in biochemical
      recurrence between the screening and control arms. * Limitations of the present
      study include lead-time bias and non-randomised treatment selection. CONCLUSIONS:
      * After RP, screen-detected cases had significantly improved PFS, MFS and CSS
      compared with controls within the available follow-up time. * The screening arm
      remained significantly associated with lower rates of biochemical recurrence and
      metastasis after adjusting for other preoperative variables. * However,
      considering also RP pathology, the improved outcomes in the screening group
      appeared to be mediated by a significantly lower tumour volume.

PMID- 22998183
TI  - Chromatin organizer SATB1 as a novel molecular target for cancer therapy.
AB  - Cancer progression and metastasis involve series of alterations in the expression
      of multitude of genes. The structure and organization of chromatin play an
      important role in spatial arrangement of genes inside the nucleus thereby
      allowing different machineries to activate or silence the transcription of genes
      governed by various epigenetic events. Epigenetic modifications and dynamic
      changes in chromatin organization by organizer proteins have recently been shown
      to play an instrumental role in regulating cancer-promoting genes. Special AT
      rich binding protein (SATB1) is a unique type of global regulator that integrates
      higher-order chromatin organization with regulation of gene expression. Aberrant
      expression of SATB1 has been shown to promote breast, hepatocellular, prostate
      and various other cancers. In this review we highlight upon the role of SATB1in
      chromatin organization and as global regulator of gene expression during cancer
      development. The expression of SATB1 progressively increases with the progression
      of cancers and it dynamically reprograms the expression of genes that are
      involved in epithelial-mesenchymal transition. SATB1 directly regulates the
      expression of ERRB2, MMP2, ABL1, E-cadherin and hence acts as key regulator in
      cancer development. Understanding the molecular mechanisms of regulation of SATB1
      expression would therefore be extremely essential towards designing strategies to
      control it. Recent studies have provided important insights into regulation of
      SATB1 by FOXP3 and microRNAs. In this review we evaluate the potential of SATB1
      as molecular target for cancer therapy.

PMID- 22998184
TI  - The retinoblastoma protein: functions beyond the G1-S regulator.
AB  - Retinoblastoma protein (pRB) is functionally inactivated in a large number of
      tumors including retinoblastoma, osteosarcoma, small-cell lung carcinoma, as well
      as bladder, breast and prostate cancers. The best known role of pRB in preventing
      cancer is inhibition of cell cycle progression by controlling the exit from the
      cell cycle into G0/G1. In addition, increasing evidence has suggested that pRB
      has important roles in DNA replication during S phase and G2/M transition. The
      tumor suppressor function of pRB has also been demonstrated by directly promoting
      differentiation via cell cycle exit with specific gene expression. Inactivation
      of pRB function during these cell cycle phases leads to dysregulated cell
      proliferation and/or chromosomal instability, which are strongly linked to cancer
      development. Thus pRB plays important roles through multiple functions in
      determining cell fate, i.e., normal growth/death and differentiation, or tumor
      formation. Therapeutic intervention by reactivation of pRB function would be
      expected to be an effective treatment against various cancers.

PMID- 22998185
TI  - Regulation of DNA replication licensing.
AB  - In eukaryotic cells, DNA replication is tightly regulated to occur only once per
      cell cycle. DNA licensing is a mechanism to guarantee this aim; that is,
      licensing of replication initiation is permitted during late M phase to G1 phase.
      The license is canceled by the start of DNA replication. Once DNA replication
      begins, the license is never given until the next late M phase. The licensing
      corresponds to the process of assembling components of the pre-replication
      complex (pre-RC) on the replication origin DNA. This pre-RC is the target of
      several different regulation systems to prevent rereplication of DNA during a
      single cell cycle. In this review, the regulation mechanisms mainly in mammals to
      control assembling components of the pre-RC will be discussed.

PMID- 22998186
TI  - Emerging roles of mitochondrial p53 and ARF.
AB  - After mitochondria colonized eukaryotic cells more than a billion years ago, they
      acquired numerous functions over the course of evolution, such as those involved
      in controlling apoptosis, autophagy, and cellular metabolism together with host
      cells. The major tumor suppressors, p53 and ARF in the nucleus also participate
      in such crosstalk between host cells and mitochondria by activating p53 target
      genes involved in varied mitochondrial functions. However, recent evidence
      suggests that p53 and ARF can also directly localize to mitochondria and
      contribute to this cross talk to maintain tissue homeostasis for the prevention
      of various diseases. Here, we discuss the functions of mitochondrial p53 and ARF
      via interactions with mitochondrial proteins as well as the mechanism of the
      localization of p53 and ARF to mitochondria. Because mitochondrial dysregulation
      is involved in the development of several disease types, such as cancer,
      neurodegenerative diseases, and age-related diseases, understanding the roles of
      p53 and ARF in mitochondria may facilitate the development of novel mitochondrial
      specific drug targets against such diseases.

PMID- 22998187
TI  - The SCF ubiquitin ligases involved in hematopoietic lineage.
AB  - The ubiquitin-proteasome system is involved in various cellular functions by
      regulating protein degradation. It has been shown previously that the SCF-type
      ubiquitin (E3) ligases are involved in cell cycle control. Here we review E3
      ligases playing the crucial roles in the determination of cell fate during
      hematopoiesis. SCFSkp2 controls the degradation of CDK inhibitors, such as p21,
      p27 and p57, to regulate hematopoietic stem cell lineage. SCFFbw7 targets several
      important proteins involved in hematopoiesis such as c-Myc, Notch and c-Myb. By
      controlling the precise levels of these proteins, E3 ligases are required for
      accurately determining hematopoietic lineage.

PMID- 22998188
TI  - The role of chromatin reorganization in the process of cellular senescence.
AB  - Cellular senescence is a state of irreversible growth arrest and thought to be a
      tumor suppressive mechanism. In addition, it has been reported that cellular
      senescence may play an important role in wound healing, tissue remodeling,
      organismal aging and age-related diseases. This loss of ability to divide,
      associated with senescence, is induced by factors that are intrinsic, such as
      genetically defined pathways and telomere erosion, and extrinsic eg. DNA damage,
      oxidative stress, over-expression of oncogenes and inadequate growth conditions.
      The p53/p21 and RB/p16 pathways are key to the cell cycle arrest associated with
      cellular senescence. Extensive molecular changes occur when cells become
      senescent, as gene expression profiling of senescent versus young cells has
      demonstrated, and this is, in part, due to alterations in chromatin structure.
      Here, we review the molecular basis of the cell cycle arrest in cellular
      senescence, focusing on chromatin regulation. We also summarize our current
      knowledge of the role of cellular senescence in vivo.

PMID- 22998190
TI  - Recommendations for utilizing and reporting population genetic analyses: the
      reproducibility of genetic clustering using the program STRUCTURE.
AB  - Reproducibility is the benchmark for results and conclusions drawn from
      scientific studies, but systematic studies on the reproducibility of scientific
      results are surprisingly rare. Moreover, many modern statistical methods make use
      of 'random walk' model fitting procedures, and these are inherently stochastic in
      their output. Does the combination of these statistical procedures and current
      standards of data archiving and method reporting permit the reproduction of the
      authors' results? To test this, we reanalysed data sets gathered from papers
      using the software package STRUCTURE to identify genetically similar clusters of
      individuals. We find that reproducing structure results can be difficult despite
      the straightforward requirements of the program. Our results indicate that 30% of
      analyses were unable to reproduce the same number of population clusters. To
      improve this, we make recommendations for future use of the software and for
      reporting STRUCTURE analyses and results in published works.

PMID- 22998191
TI  - Serum and cerebrospinal fluid urate levels in synucleinopathies versus
      tauopathies.
AB  - BACKGROUND: Low levels of serum urate are associated with a higher risk of
      Parkinson's disease (PD). Higher serum and cerebrospinal fluid (CSF) urate levels
      are associated with slower rates of clinical decline in PD and in multiple system
      atrophy (MSA). AIMS: To compare CSF and blood urate levels in healthy controls,
      patients with synucleinopathies and with tauopathies. METHODS: We investigated
      urate levels in serum and CSF from 18 healthy controls, 19 patients with
      synucleinopathies (six patients with PD and 13 with MSA), and 24 patients with
      tauopathies (18 with progressive supranuclear palsy and six with corticobasal
      degeneration). None of the patients were treated with dopaminergic medications.
      RESULTS: No significant differences were seen when comparing serum and CSF urate
      levels from controls across the parkinsonian diagnostic groups. However, in men,
      serum urate levels were significantly lower in the synucleinopathy group compared
      with the tauopathy group (P = 0.046), although with a broad overlap. CONCLUSION:
      Our study suggests that urate levels might provide new insights into the
      potential pathophysiological mechanisms underlying Parkinsonism and thereby
      contribute to the future management of these disorders.

PMID- 22998189
TI  - Ty1 gag enhances the stability and nuclear export of Ty1 mRNA.
AB  - Retrotransposon and retroviral RNA delivery to particle assembly sites is
      essential for their replication. mRNA and Gag from the Ty1 retrotransposon
      colocalize in cytoplasmic foci, which are required for transposition and may be
      the sites for virus-like particle (VLP) assembly. To determine which Ty1
      components are required to form mRNA/Gag foci, localization studies were
      performed in a Ty1-less strain expressing galactose-inducible Ty1 plasmids
      (pGTy1) containing mutations in GAG or POL. Ty1 mRNA/Gag foci remained unaltered
      in mutants defective in Ty1 protease (PR) or deleted for POL. However, Ty1 mRNA
      containing a frameshift mutation (Ty1fs) that prevents the synthesis of all
      proteins accumulated in the nucleus. Ty1fs RNA showed a decrease in stability
      that was mediated by the cytoplasmic exosome, nonsense-mediated decay (NMD) and
      the processing body. Localization of Ty1fs RNA remained unchanged in an nmd2Delta
      mutant. When Gag and Ty1fs mRNA were expressed independently, Gag provided in
      trans increased Ty1fs RNA level and restored localization of Ty1fs RNA in
      cytoplasmic foci. Endogenously expressed Gag also localized to the nuclear
      periphery independent of RNA export. These results suggest that Gag is required
      for Ty1 mRNA stability, efficient nuclear export and localization into
      cytoplasmic foci.

PMID- 22998192
TI  - Editors and researchers beware: calculating response rates in random digit dial
      health surveys.
AB  - OBJECTIVE: To demonstrate that different approaches to handling cases of unknown
      eligibility in random digit dial health surveys can contribute to significant
      differences in response rates. DATA SOURCE: Primary survey data of individuals
      with chronic disease. STUDY DESIGN: We computed response rates using various
      approaches, each of which make different assumptions about the disposition of
      cases of unknown eligibility. DATA COLLECTION: Data were collected via telephone
      interviews as part of the Aligning Forces for Quality (AF4Q) consumer survey, a
      representative survey of adults with chronic illnesses in 17 communities and
      nationally. PRINCIPAL FINDINGS: We found that various approaches to estimating
      eligibility rates can lead to substantially different response rates.
      CONCLUSIONS: Health services researchers must consider strategies to standardize
      response rate reporting, enter into a dialog related to why response rate
      reporting is important, and begin to utilize alternate methods for demonstrating
      that survey data are valid and reliable.

PMID- 22998194
TI  - Stiff skin syndrome in a newborn infant.

PMID- 22998195
TI  - Fly in Fly out and Drive in Drive out: useful contribution or worrying trend?

PMID- 22998193
TI  - Evidence for the transmission of parvovirus B19 in patients with bleeding
      disorders treated with plasma-derived factor concentrates in the era of nucleic
      acid test screening.
AB  - BACKGROUND: Parvovirus B19 (B19V) is a small, nonenveloped virus that typically
      causes a benign flu-like illness that occurs most frequently in childhood. The
      virus is resistant to current viral inactivation steps used in the manufacture of
      antihemophilic factor concentrates and B19V transmission through these products
      has been documented. Since 2000, B19V nucleic acid test (NAT) screening of plasma
      pools has been implemented to further decrease the viral burden in these
      products, but no study has examined populations using these products to assess
      the impact of the screening on B19V transmission. STUDY DESIGN AND METHODS: Blood
      specimens obtained from participants of a surveillance system established in
      federally supported specialized bleeding disorders clinics were used in a B19V
      seroprevalence study. RESULTS: A total of 1643 specimens from 1043 participants
      age 2 to 7 years born after B19V NAT screening was implemented were tested. Age
      specific prevalence rates were generally higher for subjects exposed to either
      plasma-derived products alone or in combination with other products compared to
      subjects with no exposure to antihemophilic products. Overall, compared to
      participants unexposed to blood or blood products, those exposed to plasma
      derived products alone were 1.7 times more likely to have antibodies to B19V (p =
      0.002). CONCLUSION: These results are consistent with continued B19V transmission
      through plasma-derived factor concentrates. Effective viral inactivation and
      detection processes are needed to protect users of these products from infection
      with B19V or other new or emerging viruses.

PMID- 22998196
TI  - Rural health professions can change the world.

PMID- 22998197
TI  - Culture and rural health.
AB  - This paper considers the role of culture in rural health, suggesting that the
      concept and its impacts are insufficiently understood and studied. It reviews
      some of the ways that culture has been considered in (rural) health, and states
      that culture is either used ambiguously and broadly - for example, suggesting
      that there is a rural culture, or narrowly - indeed perhaps interchangeably with
      ethnicity, for example Aboriginal culture as a unity. The paper notes that,
      although culture is a dynamic social concept, it has been adopted into a
      biomedical research paradigm as though it is fixed. Culture is often treated as
      though it is something that can be addressed simplistically, for example, through
      cultural sensitivity education. Authors suggest that culture is an unaddressed
      'elephant in the room' in rural health, and that exploring cultural differences
      and beliefs and facing up to cultural differences are vital in understanding and
      addressing rural health and health system challenges.

PMID- 22998198
TI  - Rural physical health care services for people with serious mental illness: a
      nursing perspective.
AB  - OBJECTIVE: To understand nurse perspectives on the physical health needs of their
      mental health clients and how well rural services are meeting their overall care
      needs. DESIGN: Focus groups with semistructured format. SETTING: Community mental
      health care in a regional and rural district of Queensland. PARTICIPANTS: Thirty
      eight nurses in public mental health care. RESULTS: The major themes were (i)
      stigma of mental illness, (ii) barriers to accessing physical health care
      services, (iii) nurse adaptations under demands, and (iv) community and
      integration towards better overall health. Nurses integrate overall care and
      foster its continuity for people with physical and mental co-morbidity and can be
      supported much better in sustaining this. CONCLUSION: Access and continuity of
      physical health care experienced by all Australians is exacerbated for people in
      rural areas. Physical health of people with serious mental illness residing in
      remote Australia needs to be a national health priority.

PMID- 22998199
TI  - Rural physicians' skills enrichment program: a cohort control study of retention
      in Alberta.
AB  - OBJECTIVE: The Rural Physician Action Plan of Alberta introduced an enrichment
      program in 2001 to improve physician access to skills training. The objective of
      this study was to evaluate this program and measure retention compared with
      matched controls over 5 years. DESIGN: Longitudinal, matched, case control study
      and program evaluation. SETTING: Rural communities in Alberta, Canada.
      PARTICIPANTS: Rural physicians. INTERVENTIONS: Thirty-one rural physicians self
      selected their personal skills training program and listed three goals they
      wished to attain. They were matched by age, specialty, years in practice and size
      of community with rural physicians who did not participate in a skills training
      or upgrading program. MAIN OUTCOME MEASURES: Goal attainment for subject
      physicians, use of skills at 5 years and comparison of rural retention of
      physicians at 5 years. RESULTS: Thirty-two of thirty-five physicians classified
      their goal attainment to be as expected or greater, and all were using their new
      skills at 5 years. Of the matched physicians, 29 training participants remained
      in rural practice at 5 years compared with only 22 of 29 matched control:
      relative risk 1.31, confidence interval 1.06-1.62 P < 0.05. CONCLUSIONS: The
      enrichment program provides focused, valued skills training for rural physicians
      and long-term benefits to rural communities.

PMID- 22998200
TI  - Telemedicine for rural cancer care in North Queensland: bringing cancer care
      home.
AB  - OBJECTIVE: To describe the use of telemedicine in cancer care (teleoncology model
      of care) for rural patients in North Queensland. DESIGN: This is a descriptive
      study. Data on demographical and clinical factors were retrieved from the
      teleoncology database of Townsville Hospital and review of medical records for
      the period between May 2007 and May 2011. SETTING AND PARTICIPANTS: The medical
      oncologists at the Townsville Cancer Centre, a regional cancer centre in North
      Queensland, have been providing their services to rural hospitals in Townsville
      and Mt Isa districts via videoconferencing since 2007. INTERVENTION:   Cancer
      care delivery to rural sites via Townsville teleoncology model. MAIN OUTCOME
      MEASURES: The ability of the teleoncology model to provide the following services
      to rural towns: (i) specialist consultations; (ii) urgent specialist medical
      care; (iii) care for Indigenous patients; and (iv) remote supervision of
      chemotherapy administration. RESULTS: Between May 2007 and May 2011, 158 patients
      from 18 rural towns received a total of 745 consultations. Ten of these patients
      were consulted urgently and treatment plans initiated locally, avoiding
      interhospital transfers. Eighteen Indigenous patients received consultative
      services, being accompanied by more than four to six family members. Eighty-three
      patients received a range of intravenous and oral chemotherapy regimens in Mt Isa
      and oral agents in other towns through remote supervision by medical oncologists
      from Townsville. CONCLUSION: Teleoncology model of care allows rural and
      Indigenous cancer patients to receive specialist consultations and chemotherapy
      treatments closer to home, thus minimising the access difficulties faced by the
      rural sector.

PMID- 22998201
TI  - Teleoncology for indigenous patients: the responses of patients and health
      workers.
AB  - PROBLEM: Townsville Cancer Centre provides video-consultation (VC) services to
      patients in rural/remote regions of North Queensland in order to improve access
      to specialist cancer care. The experience and responses of indigenous patients
      using this service have not been studied. Our objective is to assess the level of
      satisfaction and the responses of Indigenous patients, their families and health
      workers (HWs) to VC and such teleoncology service. DESIGN: Descriptive study,
      using semistructured interviews. SETTING: Tertiary referral centre (Townsville
      Cancer Centre) and various rural and remote towns in Queensland. KEY MEASURES FOR
      IMPROVEMENT: Satisfaction levels of Indigenous patients, their family members and
      Indigenous HWs with various aspects of the teleoncology service. LESSONS LEARNT:
      Our evaluation suggests that teleoncology is an acceptable model of care for
      Indigenous patients, with high levels of satisfaction expressed from patients,
      families and HWs. Health professionals involved with providing this service need
      to be adaptive to the needs of individual patients and local communities in order
      to provide culturally appropriate care. Formal skills training for staff,
      effective communication between specialist and local HWs, and informed consent
      procedures are essential to maintain safety of practices. Strategies for change
      are: * Mandatory informed consent procedure for all patients offered with VC. *
      Formalised competency training for staff in skills essential to maintain safe
      practices in teleoncology. * Clear clinical documentation to facilitate improved
      communication in patient management between medical staff at main centre and
      distant sites. * Further efforts in promotion, education and support for staff to
      participate in telemedicine.

PMID- 22998202
TI  - The FIRST2ACT simulation program improves nursing practice in a rural Australian
      hospital.
AB  - OBJECTIVE: To measure the impact of the Feedback Incorporating Review and
      Simulation Techniques to Act on Clinical Trends (FIRST(2) ACT) simulation program
      on nursing observations and practice relevant to patient deterioration in a rural
      Australian hospital. DESIGN: Interrupted time series analysis. SETTING: A rural
      Australian hospital. PARTICIPANTS: All registered nurses (Division 1) employed on
      an acute medical/surgical ward. INTERVENTION: The FIRST(2) ACT simulation
      program. OUTCOME MEASURES: Appropriate frequency of a range of observations and
      administration of oxygen therapy. RESULTS: Thirty-four nurses participated (83%
      of eligible nurses) in the FIRST(2) ACT program, and 258 records were audited
      before the program and 242 records after. There were statistically significant
      reductions in less than satisfactory frequency of observations (P = 0.009) and
      pain score charting (P = 0.003). There was no measurable improvement in the
      administration of oxygen therapy (P = 0.143), while the incidence of
      inappropriate nursing practice for other measures both before and after the
      intervention was too low to warrant analysis. CONCLUSION: FIRST(2) ACT was
      associated with measurable improvements in nursing practice.

PMID- 22998203
TI  - Balance outcomes from two small rural hospitals.
AB  - OBJECTIVES: To describe predicted and measured balance changes in patients
      receiving physiotherapy in two rural hospitals, and to explore the relationship
      among balance at discharge, carer availability and patients' discharge
      destination. DESIGN: Prospective measurement study. SETTING: Two rural Australian
      hospitals. PARTICIPANTS: Eighty-nine inpatients with a median age of 84. MAIN
      OUTCOME MEASURES: Berg Balance Scale (BBS) on admission and the treating
      physiotherapist's estimate at admission of individual patient's discharge BBS.
      Follow-up measures included discharge BBS, carer availability after discharge and
      patient discharge destination. RESULTS: Although change in measured balance of
      study participants had wide variability, balance measured by the BBS displayed a
      statistically and clinically significant improvement. A strong relationship was
      found between balance scores and discharge destination. However, no relationship
      was found between carer availability and discharge destination. Physiotherapists'
      estimates of discharge BBS displayed an average error of 7/56. CONCLUSIONS: The
      strong relationship between measured balance and discharge destination in these
      elderly study participants suggests that maximising their balance might minimise
      admissions to nursing home. The high variability of measured balance change
      suggests outcomes are difficult to predict. The study results suggest that
      premature assessment of patient's suitability for nursing home placement should
      be avoided. The accuracy of physiotherapist's estimates of discharge BBS suggests
      that greater weight might be placed on their input to facilitate the discharge
      planning process.

PMID- 22998204
TI  - Australian rural maternity services: creating a future or putting the last nail
      in the coffin.

PMID- 22998205
TI  - Introducing the New England 4G framework of guided self-health for people in
      rural areas with physical and psychological conditions.

PMID- 22998207
TI  - Citizens kan.

PMID- 22998208
TI  - Refractive change after vitrectomy for epiretinal membrane in pseudophakic eyes.
AB  - PURPOSE: To report the change in refraction in pseudophakic eyes following 23
      gauge vitrectomy for epiretinal membrane (ERM), without use of silicone oil,
      intraocular gas or scleral buckling. METHODS: Retrospective review of the records
      of 28 pseudophakic eyes in 28 patients undergoing 23-gauge pars plana vitrectomy
      for ERM. All 28 eyes had a measured preoperative refraction in their records and
      were seen minimum 2 months after vitrectomy for measuring their refraction.
      Fellow eyes (28 eyes) were used as controls. RESULTS: The mean preoperative
      refraction was -0.15 +/- 0.85 dioptre (D), and the mean postoperative refraction
      was -0.41 +/- 0.93 D. Thus, a myopic shift was observed following vitrectomy with
      a mean change in refraction of -0.26 +/- 0.60 D (range +0.75 to -2.13 D, p =
      0.032). The postoperative change in refraction was within +/-0.25, +/-0.50 and +/
      1.00 D in 39%, 68% and 96% of the eyes, respectively. The mean absolute
      refractive error was 0.47 +/- 0.44 D. The change in refraction in fellow eyes was
      +0.01 D (p = 0.82). CONCLUSION: The change in refraction following 23-gauge pars
      plana vitrectomy for ERM in pseudophakic eyes was -0.26 D.

PMID- 22998209
TI  - Association between ABCB1 genotype and seizure outcome in Collies with epilepsy.
AB  - BACKGROUND: Medically refractory seizures are an important problem in both humans
      and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p
      glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy.
      HYPOTHESIS: Heterogeneity of the ABCB1 gene is associated with seizure outcome in
      dogs with epilepsy. ANIMALS: Twenty-nine Collies with epilepsy being treated with
      antiepileptic drugs (AEDs). METHODS: Prospective and retrospective cohort study.
      Dogs were classified as having a good outcome (<= 1 seizure/month, no cluster
      seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures)
      based on owner-completed questionnaire. Serum AED concentrations were measured,
      and ABCB1 genotyping was performed on buccal tissue samples. Association analyses
      were performed for genotype and seizure outcome, number of AEDs administered,
      serum AED concentrations, and incidence of adverse effects. RESULTS: Fourteen
      dogs of 29 (48%) were homozygous for the ABCB1-1? mutation (M/M), 11 dogs (38%)
      were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs
      with the M/M genotype were significantly more likely to have fewer seizures and
      have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001,
      respectively). Serum phenobarbital and bromide concentrations did not differ
      between groups, but the M/N and N/N groups received a larger number of AEDs than
      the M/M group (P = .014). CONCLUSIONS AND CLINICAL IMPORTANCE: ABCB1 genotype is
      associated with seizure outcome in Collies with epilepsy. This cannot be
      attributed to differences in PGP function, but might be because of intrinsic
      variations in seizure severity among phenotypes.

PMID- 22998210
TI  - A four-stage model explaining the higher risk of Type 2 diabetes mellitus in
      South Asians compared with European populations.
AB  - With approximately 1.5 billion people at risk, the staggeringly high risk of Type
      2 diabetes in South Asians comprises a global problem. The causes of this high
      risk are complex, with 23 major risk factors identified in a Lancet seminar. This
      paper proposes a four-stage explanatory model: (1) the birth of a small, adipose,
      lowlean mass South Asian baby--the phenotype tracking through life; (2) in
      childhood and early adulthood, the deposition of any excess energy intake
      preferentially in upper body and ectopic fat stores rather than in the lower body
      or superficial subcutaneous fat stores; (3) as a consequence of points 1 and 2,
      and exacerbated by an environment of low physical activity and excess calories,
      the accelerated appearance of high levels of plasma insulin, triglycerides and
      glucose, and the fatty-liver vicious cycle; (4) beta-cell failure as a result of
      fewer beta-cells at birth, exposure to apoptotic triggers such as fat in the
      pancreas, and high demand from insulin resistance, which causes diabetes. Other
      risk factors--especially energy-dense hyperglycaemic diet and low physical
      activity--play into this pathway. The recommended behavioural changes fit with
      this model, which brings clarity to guide future research, policy, practice and
      health promotion.

PMID- 22998211
TI  - Following the wetting of one-dimensional photoactive surfaces.
AB  - This article aims toward a full description of the wetting conversion from
      superhydrophobicity to superhydrophilicity under illumination with UV light of
      high-density ZnO nanorods surfaces by (i) following the evolution of the clusters
      and superstructures formed by the nanocarpet effect as a function of the water
      contact angle (WCA); (ii) characterization of the superhydrophobic and
      superhydrophilic states with an environmental scanning electron microscope
      (ESEM); and (iii) using the nanocarpet effect as a footprint of both local and
      apparent water contact angles. Thus, the main objective of the article is to
      provide a general vision of the wettability of 1D photoactive surfaces. In
      parallel, the nanocarpet (NC) formation by clustering of vertically aligned ZnO
      nanorods (NR) when water is dripped on their surface and then dried is studied
      for the first time by taking advantage of the possibility of tuning the surface
      water contact angle of the ZnO NR structure under UV preillumination. As a
      result, we demonstrate the feasibility of controlling the size and other
      morphological characteristics of the NCs. Moreover, a strong anisotropic wetting
      behavior, characterized by a Deltatheta = theta(parallel) - theta(perpendicular)
      = 30 degrees , is shown on an asymmetrically aligned NC surface resulting from
      arrays of tilted NRs. The study of the condensation/evaporation of water on/from
      an as-prepared (superhydrophobic) or a preilluminated (superhydrophilic) NR
      surface examined by an environmental scanning electron microscope has evidenced
      the formation of supported water droplets with polygonal shapes in the first case
      and the complete filling of the inter-NR space in the latter. The long-term
      stability of the NC clusters has been utilized as a footprint to track the
      penetration depth of water within the inter-NR space in the three borderline
      regions of water droplets. This analysis has shown that for moderately
      hydrophobic surfaces (i.e., water contact angles lower than 130 degrees ) water
      droplets do not present a well-defined borderline trace but a spreading region
      where water penetrates differently with the NR interspace. The transition from a
      Cassie-Baxter to a modified Cassie-Baxter to finish in a Wenzel wetting state is
      found on these surfaces depending on the UV preillumination time and is explained
      with a model where water interaction with the NR units is the critical factor
      determining the macroscopic wetting behavior of these surfaces.

PMID- 22998212
TI  - Mass spectrometric characterization of protein adducts of multiple P450-dependent
      reactive intermediates of diclofenac to human glutathione-S-transferase P1-1.
AB  - Use of the nonsteroidal anti-inflammatory drug diclofenac (DF) is associated with
      serious idiosyncratic hepatotoxicity. Covalent binding of reactive intermediates
      of DF to proteins is considered to initiate the process leading to this severe
      side-effect. The aim of this study was to characterize the nature of covalent
      protein modifications by reactive metabolites of DF which result from
      bioactivation by cytochrome P450. DF and its major monohydroxylated metabolites
      4'-hydroxydiclofenac (4'-OH-DF) and 5-hydroxydiclofenac (5-OH-DF) were
      bioactivated using a highly active P450 BM3 mutant (CYP102A1M11H) in the presence
      of the model target protein human glutathione-S-transferase P1-1 (hGST P1-1).
      Protein-adducts were subsequently identified by LC-MS/MS analysis of tryptic
      digests of hGST P1-1. In total, 10 different peptide adducts were observed which
      result from modifications of Cys-47 and Cys-14 of hGST P1-1. The majority of the
      protein thiol modifications appeared to be derived from 5-OH-DF, which produced
      seven different peptide adducts with mass increments of 289.0, 309.0, and 339.0
      Da. Remarkably, no peptide adducts were observed upon the bioactivation of 4'-OH
      DF. Incubations of P450 BM3 with DF also showed the peptide adducts derived from
      5-OH-DF and peptide adducts that are not derived from quinone imine. A peptide
      adduct with a mass increment of 249.0 Da most likely results from the o-imine
      methide formed by oxidative decarboxylation of DF. In addition, a peptide adduct
      was observed with a mass increment of 259.0 Da, which corresponds to the
      substitution of one of the chlorine atoms of DF by protein thiol. A corresponding
      GSH-conjugate with a similar mass increment was only observed if incubations of
      DF with P450 and GSH were supplemented by human GST P1-1. The results of this
      study not only confirm the importance of 5-OH-DF in covalent protein-binding but
      also suggest that the nature of protein adduction is not necessarily reflected by
      chemical conjugation with GSH.

PMID- 22998213
TI  - Chronic calcium pyrophosphate crystal inflammatory arthritis induced by extreme
      hypomagnesemia in short bowel syndrome.
AB  - BACKGROUND: Short bowel syndrome (SBS) may induce a plethora of clinical symptoms
      ranging from underweight to nutrient-, vitamin- and electrolyte deficiencies. The
      objective of this case report is to illustrate how demanding the management of a
      60 year old patient with SBS and recurrent joint attacks was for different
      medical disciplines. CASE PRESENTATION: The patient with SBS presented with a
      body mass index of 16.5 kg/m2 after partial jejunoileal resection of the small
      intestine with a six year long history of recurrent pain attacks in multiple
      peripheral joints, chronic diarrhoea and food intolerances. Pain attacks occurred
      4-5 times a week with a median consumption of 15 mg prednisone per day. The
      interdisciplinary workup after several gastroenterologic, rheumatologic,
      radiologic, psychiatric and orthopedic consultations is shown including
      successful treatment steps.Clinical diagnosis revealed no systemic inflammatory
      disease, but confirmed extreme hypomagnesemia (0.2 mmol/l) after reproducible
      pathological magnesium resorption tests as causative for chronic calcium
      pyrophosphate crystal inflammatory arthritis (pseudogout,
      chondrocalcinosis).Multidisciplinary treatment included application of
      colchicines, parenteral nutrition and magnesium substitution, antiperistaltic
      agents and avoidance of intolerant foods. Normalization of magnesium levels and a
      marked remission of joint attacks were achieved after six months with significant
      reduction of prednisone to 1.5 mg/day. CONCLUSION: Despite the rarity of this
      condition, it is important to know that hypomagnesaemia may be associated with
      calcium pyrophosphate crystal inflammatory arthritis (chondrocalcinosis) and that
      SBS patients may be prone to develop extreme hypomagnesaemia causing recurrent
      joint attacks without systemic inflammation.

PMID- 22998215
TI  - Pharmacokinetic properties, potential herb-drug interactions and acute toxicity
      of oral Rhizoma coptidis alkaloids.
AB  - INTRODUCTION: Rhizoma coptidis shows various pharmacological activities
      attributed to its alkaloid constituents. To guide the pharmacological studies,
      the candidate drug research and development and the clinic applications of these
      compounds, a review on their pharmacokinetic behavior and toxicity should be
      beneficial. AREAS COVERED: This article looks at the pharmacokinetic properties
      and potential herb-drug interactions found with Rhizoma coptidis alkaloids.
      Furthermore, the article also reviews the acute toxicity of these alkaloids.
      EXPERT OPINION: Generally, the systemic exposures of the alkaloids are extremely
      low after oral administration. The alkaloids may present their systemic
      activities via generated metabolites and/or the tissue distributed alkaloids
      themselves, or by modulating effectors in the gut. The drug transporters and drug
      metabolizing enzymes involved in the in vivo process, the modulatory effects on
      both P-glycoprotein and cytochrome P450 isoenzymes and the acute toxicity of the
      alkaloids were all well documented. However, first, since very significant
      difference exists between the blood and tissue exposure, to find suitable
      pharmacokinetic markers of the alkaloids in blood may be challenging but
      necessary. Second, the dose-systemic exposure-response relationships of the
      alkaloids should also be determined. Third, in order to improve the oral
      bioavailability and efficacy, it is important to design derivatives or
      formulations of the alkaloids with better pharmacokinetic features.

PMID- 22998216
TI  - Protective effect of Hypericum hircinum on doxorubicin-induced cardiotoxicity in
      rats.
AB  - Oxidative stress is the main factor in doxorubicin (DOX) induced cardiotoxicity.
      Wistar rats received either DOX (3 mg kg-1, i.p.) every other day or combination
      of Hypericum hircinum (100 and 200 mg kg-1, p.o.) and DOX or H. hircinum (200 mg
      kg-1, p.o.) extract alone for 2 weeks. Cardiotoxicity was assessed by recording
      changes in ECG, heart rate and measuring the levels of cardiac marker enzymes-
      lactic acid dehydrogenase, creatine phosphokinase, glutamic oxaloacetic
      transaminase, the antioxidant defence enzymes--reduced glutathione (GSH),
      superoxide dismutase (SOD) and lipid peroxidative value (LPO) at the end of
      treatment schedule. Treatment with H. hircinum significantly (p < 0.05) decreased
      the levels of LPO and marker enzymes, increased the levels of GSH and SOD,
      reversed the changes in ECG and prevented the decrease in heart weight in DOX
      treated group. The results suggest that H. hircinum has the potential to prevent
      the cardiotoxic effects induced by DOX.

PMID- 22998217
TI  - Sorting of lipidated peptides in fluid bilayers: a molecular-level investigation.
AB  - Nearest-neighbor recognition (NNR) measurements have been made for two lipidated
      forms of GlyCys, interacting with analogues of cholesterol and 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC) in the liquid-ordered (l(o)) and liquid
      disordered (l(d)) phases. Interaction free energies that have been determined
      from these measurements have been used in Monte Carlo simulations to quantify the
      distribution of the peptides between liquid-ordered and liquid-disordered
      regions. These simulations have shown that significant differences in the lipid
      chains have a very weak influence on the partitioning of the peptide between
      these two phases. They have also revealed an insensitivity of the peptide
      partition coefficient, K(p), to the size of the l(o) and l(d) domains that are
      present. In a broader context, these findings strongly suggest that the sorting
      of peripheral proteins in cellular membranes via differential lipidation may be
      more subtle than previously thought.

PMID- 22998218
TI  - The rust transferred proteins-a new family of effector proteins exhibiting
      protease inhibitor function.
AB  - Only few fungal effectors have been described to be delivered into the host cell
      during obligate biotrophic interactions. RTP1p, from the rust fungi Uromyces
      fabae and U. striatus, was the first fungal protein for which localization within
      the host cytoplasm could be demonstrated directly. We investigated the occurrence
      of RTP1 homologues in rust fungi and examined the structural and biochemical
      characteristics of the corresponding gene products. The analysis of 28 homologues
      showed that members of the RTP family are most likely to occur ubiquitously in
      rust fungi and to be specific to the order Pucciniales. Sequence analyses
      indicated that the structure of the RTPp effectors is bipartite, consisting of a
      variable N-terminus and a conserved and structured C-terminus. The
      characterization of Uf-RTP1p mutants showed that four conserved cysteine residues
      sustain structural stability. Furthermore, the C-terminal domain exhibits
      similarities to that of cysteine protease inhibitors, and it was shown that Uf
      RTP1p and Us-RTP1p are able to inhibit proteolytic activity in Pichia pastoris
      culture supernatants. We conclude that the RTP1p homologues constitute a rust
      fungi-specific family of modular effector proteins comprising an unstructured N
      terminal domain and a structured C-terminal domain, which exhibit protease
      inhibitory activity possibly associated with effector function during biotrophic
      interactions.

PMID- 22998219
TI  - Induction thermal plasma process modifies the physicochemical properties of
      materials used for carbon nanotube production, influencing their cytotoxicity.
AB  - The effect of radio frequency induction thermal plasma (RFITP) process on the
      cytotoxicity of materials used for single-walled carbon nanotube production
      remains unknown. In this study, the influence of RFITP process on physicochemical
      and cytotoxic properties of commercial Co, Ni, Y2O3, Mo catalysts and carbon
      black was investigated. The cytotoxic assays (MTS, LDH, neutral red, TUNEL)
      revealed the strongest effect of commercial Co on murine Swiss 3T3 fibroblasts
      affecting their viability in a dose-dependent manner within 24 h. The cells
      contained also less actin stress fibres. Although RFITP affects the properties of
      each catalyst (size, morphology, chemistry), only cytotoxicity of Ni catalyst was
      increased. The plasma-treated Ni induced apoptosis. Comparing Ni particles before
      and after RFITP process with commercial nanoparticles of Ni revealed that the
      particles with similar surface area have different cytotoxicities. Interestingly,
      the observed toxicity of the catalysts was not mainly due to the release of ions.

PMID- 22998220
TI  - The number of regulatory T cells correlates with hemodynamic improvement in
      patients with inflammatory dilated cardiomyopathy after immunoadsorption therapy.
AB  - Inflammatory DCM (iDCM) may be related to autoimmune processes. An
      immunoadsorption (IA) has been reported to improve cardiac hemodynamics. The
      benefit of IA is probably related to the removal of autoantibodies. A recent
      study suggests additional effects of IA on the T cell-mediated immune reactions,
      especially on regulatory T cells (Tregs). In this prospective study, the
      correlation between the level of Tregs and improvement of myocardial
      contractility in response to IA in patients with iDCM was investigated. Patients
      (n = 18) with iDCM, reduced left ventricular (LV) ejection fraction (<35%), were
      enrolled for IA. Before and 6 months after IA, LV systolic function was assessed
      by echocardiography, and blood levels of Tregs were quantified by FACS analysis.
      Patients (n = 12) with chronic ischaemic heart failure and comparable reduced LV
      EF served as controls. IA improved LV-EF in 12 of 18 patients at 6-month follow
      up. These patients were classified as 'IA responder'. In 6 patients, LV-EF
      remained unchanged. At baseline, IA responder and non-responder subgroups showed
      similar values for C-reactive protein, white blood cells, lymphocytes and T
      helper cells, but they differ for the number of circulating Tregs (responder:
      2.32 +/- 1.38% versus non-responder: 4.86 +/- 0.28%; P < 0.01). Tregs increased
      significantly in the IA responders, but remained unchanged in the IA non
      responders. In patients with ischaemic cardiomyopathy, none of these values
      changed over time. A low level of Tregs in patients with chronic iDCM may
      characterize a subset of patients who do best respond to IA therapy.

PMID- 22998221
TI  - Enhanced oral bioavailability of isradipine via proniosomal systems.
AB  - The objective of the present research was to develop a proniosomal formulation of
      isradipine and to evaluate the influence of proniosomal systems on the oral
      bioavailability of the drug in albino Wistar rats. Proniosomes were prepared by
      film deposition on carrier's method using various molar ratios of nonionic
      surfactants such as span20, span40, span60, and span80 with cholesterol as
      membrane stabilizing agent and dicetylphosphate as a charge inducer. The
      formation of niosomes and surface morphology of proniosome formulations were
      studied by optical and scanning electron microscopy (SEM), respectively. The
      prepared proniosomes have shown higher dissolution of isradipine compared with
      pure drug powder. Fourier transform infrared spectroscopy, differential scanning
      calorimetry, and powder X-ray diffractometry studies were performed to understand
      the solid state properties of the drug. Ex vivo permeation enhancement assessed
      from flux, permeability coefficient, and enhancement ratio were significantly
      higher for proniosomes compared with control. The pharmacokinetic parameters were
      evaluated in male albino Wistar rats and a significant enhancement in the
      bioavailability (2.3-fold) was observed from optimized proniosome formulation
      compared with control (oral suspension). The stability study reveals that the
      proniosome formulations are stable when stored at 4 degrees C.

PMID- 22998222
TI  - Behavior of hydrophobic polyelectrolyte solution in mixed aqueous/organic
      solvents revealed by neutron scattering and viscosimetry.
AB  - We investigate in this paper the influence of the improvement of the solvent
      quality on the structure and the viscous properties of solutions of an
      hydrophobic polyelectrolyte, poly(styrene-co-sodium styrenesulfonate): PSS. The
      solvent used is a mixture of water and an organic solvent, THF, which is also
      slightly polar. We use small angle neutron scattering in the semidilute regime
      and viscosimetry as a function of concentration in dilute and semidilute
      unentangled regime. The structure, namely the scattering from all chains, is
      characterized by a maximum ("polyelectrolyte peak"). Its position and amplitude
      depends, at a given sulfonation rate of PSS, on the solvent quality through the
      added amount of organic solvent (THF). These evolutions with the THF amount are
      more pronounced when the sulfonation rate f is low (more hydrophobic
      polyelectrolyte) and the amount of added THF is high. Adding THF to hydrophobic
      PSS (f = 0.50 or f = 0.38), diminishes also the "shoulder" visible in the log I -
      log q plot and associated with the pearl size. It is therefore proposed that when
      THF is added to aqueous polyelectrolyte solutions, the pearls are dissolved and
      the chain conformation evolves from the pearl-necklace shape already reported in
      pure water toward the string-like conformation in pure water for fully sulfonated
      PSS. An addition of THF also reduces the important low q upturn found with
      hydrophobic polyelectrolyte solutions: the large aggregates are dissolved by THF.
      The upturn can become for PSSNa f = 0.38, after adding enough THF (50%), even
      smaller than that for the charged hydrophilic case PSSNa f = 0.82, in water. This
      can mean that in the quasi-fully charged PSS at f = 0.82 there are still
      hydrophobic effects in water, which is disagreeing with our recent reports, or
      that the electrostatics contribution to the upturn is reduced due to a lower
      dielectric permittivity. Concerning the hydrophilic polyelectrolyte, poly(sodium
      2-acrylamido-2-methylpropanesulfonate)-co-(acrylamide): AMAMPS, no evolution in
      structure occurs until 25% THF. The viscosimetry variation with THF fraction is
      in good agreement with the scattering one up to 25%: though little dependent on
      THF for AMAMPS, and for hydrophilic PSSNa, it increases for hydrophobic PSSNa in
      agreement with the chain expansion signaled by scattering. At 50% THF
      concentration, the hydrophilic polyelectrolyte shows new surprising behaviors:
      the scattering of PSSNa is no longer characteristic of polyelectrolytes, and
      AMAMPS solutions display an unexpected viscosity decrease.

PMID- 22998224
TI  - Detecting genes for variation in parasite burden and immunological traits in a
      wild population: testing the candidate gene approach.
AB  - Identifying the genes underlying phenotypic variation in natural populations can
      provide novel insight into the evolutionary process. The candidate gene approach
      has been applied to studies of a number of traits in various species, in an
      attempt to elucidate their genetic basis. Here, we test the application of the
      candidate gene approach to identify the loci involved in variation in
      gastrointestinal parasite burden, a complex trait likely to be controlled by many
      loci, in a wild population of Soay sheep. A comprehensive literature review, Gene
      Ontology databases, and comparative genomics resources between cattle and sheep
      were used to generate a list of candidate genes. In a pilot study, these
      candidates, along with 50 random genes, were then sequenced in two pools of Soay
      sheep; one with low gastrointestinal nematode burden and the other high, using a
      NimbleGen sequence capture experiment. Further candidates were identified from
      single nucleotide polymorphisms (SNPs) that were highly differentiated between
      high- and low-resistance sheep breeds. A panel of 192 candidate and control SNPs
      were then typed in 960 individual Soay sheep to examine whether they individually
      explained variation in parasite burden, as measured as faecal egg count, as well
      as two immune measures (Teladorsagia circumcincta-specific antibodies and
      antinuclear antibodies). The cumulative effect of the candidate and control SNPs
      were estimated by fitting genetic relationship matrices (GRMs) as random effects
      in animal models of the three traits. No more significant SNPs were identified in
      the pilot sequencing experiment and association study than expected by chance.
      Furthermore, no significant difference was found between the proportions of
      candidate or control SNPs that were found to be significantly associated with
      parasite burden/immune measures. No significant effect of the candidate or
      control gene GRMs was found. There is thus little support for the candidate gene
      approach to the identification of loci explaining variation in parasitological
      and immunological traits in this population. However, a number of SNPs explained
      significant variation in multiple traits and significant correlations were found
      between the proportions of variance explained by individual SNPs across multiple
      traits. The significant SNPs identified in this study may still, therefore, merit
      further investigation.

PMID- 22998223
TI  - Arf6 regulation of Gyrating-clathrin.
AB  - 'Gyrating-' or 'G'-clathrin are coated endocytic structures located near
      peripheral sorting endosomes (SEs), which exhibit highly dynamic but localized
      movements when visualized by live-cell microscopy. They have been implicated in
      recycling of transferrin from the sorting endosome directly to the cell surface,
      but there is no information about their formation or regulation. We show here
      that G-clathrin comprise a minority of clathrin-coated structures in the cell
      periphery and are brefeldin A (BFA)-resistant. Arf6-GTP substantially increases G
      clathrin levels, probably by lengthening coated bud lifetimes as suggested by
      photobleaching and photoactivation results, and an Arf6(Q67L)-GTP mutant bearing
      an internal GFP tag can be directly visualized in G-clathrin structures in live
      cells. Upon siRNA-mediated depletion of Arf6 or expression of Arf6(T27N), G
      clathrin levels rise and are primarily Arf1-dependent, yet still BFA-resistant.
      However, BFA-sensitive increased G-clathrin levels are observed upon acute
      incubation with cytohesin inhibitor SecinH3, indicating a shift in GEF usage.
      Depletion of both Arf6 and Arf1 abolishes G-clathrin, and results in partial
      inhibition of fast transferrin recycling consistent with the latter's
      participation in this pathway. Collectively, these results demonstrate that the
      dynamics of G-clathrin primarily requires completion of the Arf6 guanine
      nucleotide cycle, but can be regulated by multiple Arf and GEF proteins,
      reflecting both overlapping mechanisms operative in their regulation and the
      complexity of processes involved in endosomal sorting.

PMID- 22998225
TI  - Biological effects of inhaled 239PuO2 in Beagles.
AB  - Seven groups of 8-24 Beagle dogs, exposed to (239)PuO(2) aerosols by inhalation
      [mean initial lung depositions (ILD) of 0.0, 0.14, 0.63, 3.2, 13, 44 and 210 kBq]
      were observed throughout their lives to determine tissues at risk and dose-effect
      relationships. The mean average pulmonary retention half-time of (239)Pu was
      1,192 days. Most (70%) of the plutonium recovered at death in dogs surviving >10
      years after exposure was found in the thoracic lymph nodes with ~15% in lung,
      ~10% in liver and ~2% in bone. Eight dogs at the highest exposure levels died
      from radiation pneumonitis prior to a minimal 3-year latency period after
      exposure for the observation of lung tumors, with the first succumbing 337 days
      after exposure. Of 108 plutonium-exposed Beagles with ILD <100 kBq, 51 (47%) had
      lung tumors with significantly increased incidence in those dogs with total lung
      dose of >=1.1 Gy at death. The primary non-neoplastic effects observed were
      lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, radiation
      pneumonitis and pulmonary fibrosis, and bacterial pneumonia. Lesions of the
      thoracic lymph nodes were observed in 98 of 108 exposed dogs, but there were no
      primary neoplasms of the lymph nodes. Bacterial pneumonia was observed in 13
      plutonium-exposed dogs and was the most notable non-neoplastic cause of death,
      with survival nearly the same as that of controls. Setting of dose limits on the
      basis of detrimental effects commonly considers and differentiates between
      stochastic and deterministic effects, raising the question of whether the non
      neoplastic effects found in this study were deterministic. The International
      Commission on Radiation Protection (ICRP), National Council on Radiation
      Protection & Measurements (NCRP), and similar organizations generally consider
      effects that increase in incidence and severity to meet the definition of
      deterministic. We demonstrated the radiation dose-related nature of effects such
      as pneumonitis and fibrosis graphically and lymphopenia numerically, rather than
      by quantified estimates. It is clear, however, that both incidence and severity
      increased with ILD and radiation dose and should be considered as deterministic
      effects.

PMID- 22998226
TI  - Risk of thyroid cancer among chernobyl liquidators.
AB  - After the Chernobyl accident in 1986, the "liquidators" or clean-up workers were
      among those who received the highest radiation doses to the thyroid from external
      radiation. Some were also exposed to radioiodines through inhalation or
      ingestion. A collaborative case-control study nested within cohorts of
      Belarusian, Russian and Baltic liquidators was conducted to evaluate the
      radiation-induced risk of thyroid cancer. The study included 107 cases and 423
      controls. Individual doses to the thyroid from external radiation and from iodine
      131 ((131)I) were estimated for each subject. Most subjects received low doses
      (median 69 mGy). A statistically significant dose-response relationship was found
      with total thyroid dose. The Excess Relative Risk (ERR) per 100 mGy was 0.38 [95%
      confidence interval (CI): 0.10, 1.09]. The risk estimates were similar when doses
      from (131)I and external radiation were considered separately, although for
      external radiation the ERR was not statistically significantly elevated. The ERR
      was similar for micro carcinomas and larger size tumors, and for tumors with and
      without lymph node involvement. Although recall bias and uncertainties in doses
      could have affected the magnitude of the risk estimates, the findings of this
      study contribute to a better characterization the risk of thyroid cancer after
      radiation exposure in adulthood.

PMID- 22998227
TI  - Modeling cell survival after photon irradiation based on double-strand break
      clustering in megabase pair chromatin loops.
AB  - A new, simple mechanistic dose-response model for cell survival after photon
      irradiation is presented. Its ingredients are motivated by the concept of giant
      loops, which constitute a level of chromatin organization on a megabase pair
      length scale. Double-strand breaks (DSBs) that are induced within different loop
      domains of the DNA are assumed to be processed independently by the cell's repair
      mechanism. The model distinguishes between two classes of damage, characterized
      by either a single DSB or multiple DSBs within a single loop. Different repair
      fidelities are associated with these two damage classes from which lethality of
      damages and consequently the survival probability of cells is derived. Given the
      giant loop chromatin organization and the assumption of two damage classes
      represent the main pillars of this new approach, we propose to call it the Giant
      LOop Binary LEsion (GLOBLE) approach. In this paper, we discuss the motivation
      and the formulation of the model as well as some basic implications. First
      applications to experimental data obtained with 250 kV X-rays exhibit that the
      model is able to reveal important features of the dose-response curves describing
      cell survival. These comprise a linear-quadratic behavior at lower doses and a
      transition to a straight dose-response relationship at high doses. We establish
      relationships to the parameters alpha and beta of the linear-quadratic model and
      discuss possible generalizations. When expressed in terms of the linear-quadratic
      model, we demonstrate that our new model predicts an intrinsic anticorrelation
      between beta and alpha, in line with an analysis of a large set of experimental
      data that is based on survival curves for more than 150 cell lines.

PMID- 22998228
TI  - Permeability changes of cationic liposomes loaded with carbonic anhydrase induced
      by millimeter waves radiation.
AB  - The interaction of millimeter wave radiation, in the 30-300 GHz range, with
      biological systems is a topic of great interest as many of the vibrational
      dynamics that occur in biochemical reactions of large macromolecules in living
      organisms fall in the 1-100 GHz range. Membranes and cellular organelles may have
      different ways of interacting with this radiation as well. In this article, we
      investigate the influence of 53.37 GHz of radiation on lipid membrane
      permeability by using cationic liposomes that contain
      dipalmitoylphosphatidylcholine (DPPC), cholesterol and stearylamine. Carbonic
      anhydrase (CA) is loaded inside the liposome and the substrate p-nitrophenyl
      acetate (p-NPA) is added in the bulk aqueous phase. Upon permeation across the
      lipid bilayer, the trapped CA catalyzes the conversion of the p-NPA molecules
      into products. Because the self-diffusion rate of p-NPA across intact liposomes
      is very low, the CA reaction rate expressed as DeltaA/min is used to track
      membrane permeability changes. A highly significant (P < 0.0001) enhancement of
      the CA reaction rate, typically from DeltaA/min = 0.0043 +/- 0.0017 (n = 26) to
      DeltaA/min = 0.0100 +/- 0.0020 (n = 32) resulted at a low-level density power of
      0.1 mW/cm(2). The enhancement of the CA reaction rate was observed at a lesser
      extent on liposomes with a larger diameter and, in turn with leaflets less bent.
      The different packing of the phospholipid bilayer-due to the higher curvature
      could be a critical factor in eliciting membrane permeability changes indicating
      a possible role for water molecules bound to functional groups in the glycerol
      region. Since numerical dosimetry indicates that the temperature rise during the
      exposure was negligible, the observed effects cannot be attributed to heating of
      the samples.

PMID- 22998229
TI  - Bartonella spp. infection in healthy and sick horses and foals from the
      southeastern United States.
AB  - BACKGROUND: Bartonella species bacteremia has been identified in numerous animal
      species. These bacteria cause, or have been associated with, a spectrum of
      clinical manifestations in dogs and human patients. The frequency of exposure to
      or infection with Bartonella spp. among healthy and sick horses has not been
      reported. OBJECTIVE: To test healthy and sick horses and sick foals from the
      southeastern United States for serological, microbiological, and molecular
      evidence of Bartonella infection. ANIMALS: Forty-seven healthy horses, 15 sick
      foals, 22 horses with musculoskeletal manifestations, and 8 horses with colic
      were tested for Bartonella. METHODS: IFA serology and PCR before and after BAPGM
      (Bartonella alpha-Proteobacteria Growth Medium) enrichment blood culture.
      RESULTS: Bartonella antibodies were not detected in foals or horses. Three
      Bartonella species, B. henselae, B. vinsonii subsp. berkhoffii (genotypes I and
      III), and a Bartonella species with closest homology to Candidatus Bartonella
      volans, were PCR-amplified and sequenced from blood or BAPGM enrichment blood
      culture samples from 1/47 healthy horses, 3/15 sick foals, 5/22 horses with
      musculoskeletal disease, and 0/8 horses with colic. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Horses in the southeastern United States are naturally infected with
      B. henselae, B. vinsonii subsp. berkhofii genotypes I and III, and a bacteria
      most similar to Candidatus Bartonella volans. Antibodies were not detectable by
      indirect fluorescent antibody assay (IFA) testing in bacteremic foals or horses,
      and prolonged enrichment culture for periods up to 21 days were necessary to
      document bacteremia in most horses. Further investigation into the pathogenic
      potential of Bartonella spp. infection in horses is warranted.

PMID- 22998230
TI  - Chronic vulvovaginal candidiasis: what we know and what we have yet to learn.
AB  - Vulvovaginal candidiasis (VVC) is defined as vulvovaginitis, causally associated
      with Candida species in the vagina. It is seen commonly in vulval clinics as a
      cause of persistent vulvovaginitis and yet this chronic condition is yet to be
      formally defined and explained. The classic symptom complex of chronic itch, pain
      and dyspareunia exacerbating premenstrually and remitting during menstruation
      associated with an erythematous vulval eruption is well described but the exact
      aetiology remains elusive. Research in recent years has suggested that VVC is not
      an opportunistic infection or an immunodeficiency but a hypersensitivity response
      to a commensal organism that may be genetically determined. Further, it is
      apparent on clinical grounds that oestrogen plays an essential permissive role
      and that, in healthy non-diabetic patients, VVC does not occur in the absence of
      oestrogen whether endogenous or exogenous. The nature of this relationship has
      not been established. In this article I discuss the diagnostic features of VVC,
      its management and what is currently understood of its aetiology.

PMID- 22998231
TI  - California's minimum nurse staffing legislation: results from a natural
      experiment.
AB  - OBJECTIVE: To determine whether, following implementation of California's minimum
      nurse staffing legislation, changes in acuity-adjusted nurse staffing and quality
      of care in California hospitals outpaced similar changes in hospitals in
      comparison states without such regulations. DATA SOURCES/STUDY SETTING: Data from
      the American Hospital Association Annual Survey of Hospitals, the California
      Office of Statewide Health Planning and Development, the Hospital Cost Report
      Information System, and the Agency for Healthcare Research and Quality's Health
      Care Cost and Utilization Project's State Inpatient Databases from 2000 to 2006.
      STUDY DESIGN: We grouped hospitals into quartiles based on their preregulation
      staffing levels and used a difference-in-difference approach to compare changes
      in staffing and in quality of care in California hospitals to changes over the
      same time period in hospitals in 12 comparison states without minimum staffing
      legislation. DATA COLLECTION/EXTRACTION METHODS: We merged data from the above
      data sources to obtain measures of nurse staffing and quality of care. We used
      Agency for Healthcare Research and Quality's Patient Safety Indicators to measure
      quality. PRINCIPAL FINDINGS: With few exceptions, California hospitals increased
      nurse staffing levels over time significantly more than did comparison state
      hospitals. Failure to rescue decreased significantly more in some California
      hospitals, and infections due to medical care increased significantly more in
      some California hospitals than in comparison state hospitals. There were no
      statistically significant changes in either respiratory failure or postoperative
      sepsis. CONCLUSIONS: Following implementation of California's minimum nurse
      staffing legislation, nurse staffing in California increased significantly more
      than it did in comparison states' hospitals, but the extent of the increases
      depended upon preregulation staffing levels; there were mixed effects on quality.

PMID- 22998232
TI  - Speeding up a bidirectional DNA walking device.
AB  - A strategy to speed up DNA walking devices through the use of DNA catalysts has
      been developed. The DNA walker is designed to move on a three-foothold molecular
      track with the assistance of fuel strands. The movement can be accelerated in the
      presence of catalysts. The motor could be halted at a desired location by a
      simple control, and the locomotion is about 1 order of magnitude faster than
      previous hybridization-based walker. Additionally, one branch of the walker can
      be designed to capture and transfer protein or some other inorganic molecules
      along the designed track with easy control, which makes our engineered DNA system
      more versatile.

PMID- 22998233
TI  - Systemic lupus erythematosus with dystrophic calcifications.

PMID- 22998234
TI  - Effect of anxiety and depression on the recurrence of paroxysmal atrial
      fibrillation after circumferential pulmonary vein ablation.
AB  - Effect of Anxiety and Depression on the Recurrence of Paroxysmal Atrial
      Fibrillation. INTRODUCTION: Whether circumferential pulmonary vein ablation
      (CPVA) can alleviate anxiety and depression symptoms is unknown and the effect of
      anxiety and depression on the recurrence of atrial fibrillation (AF) after CPVA
      is not clear. METHODS: Two hundred and ten patients with a diagnosis of
      paroxysmal AF were admitted in the study. Ninety-eight patients (CPVA group) and
      102 patients (medicine group) were treated with CPVA and antiarrhythmic drugs,
      respectively. All patients were followed up for 1 year. Zung Self-Rating Anxiety
      Scale (SAS), Zung Self-Rating Depression Scale (SDS), and Short-Form life survey
      36 items (SF-36) were assessed before and after follow-up. RESULTS: In CPVA
      group, the scores of SAS and SDS decreased (41.69 +/- 8.32 vs 37.66 +/- 4.82, P <
      0.001 and 45.01 +/- 9.71 vs 40.05 +/- 8.56, P < 0.001, respectively) and SF-36
      score improved (565.29 +/- 143.37 vs 606.84 +/- 102.84, P = 0.021) after follow
      up. Compared with the data in recurrent patients, the SAS and SDS scores were
      significantly lower in nonrecurrent patients at baseline (44.68 +/- 8.40 vs 38.10
      +/- 7.55, P < 0.001 and 51.75 +/- 9.41 vs 43.96 +/- 8.95, P < 0.001,
      respectively). The results of multivariate logistic regression analysis showed
      normalized scores of SAS (OR = 3.20, 95% CI [3.05, 3.48], P = 0.023) and SDS (OR
      = 3.26, 95% CI [3.12, 3.49], P = 0.023) were the independent risk factor of AF
      recurrence after CPVA. CONCLUSIONS: CPVA can ameliorate anxiety and depression,
      which may contribute to improvement of quality of life in patients with
      paroxysmal AF. Anxiety and depression increase the recurrence risk of AF after
      CPVA.

PMID- 22998235
TI  - Long term monitoring of three automated HIV 4th generation combined
      antibody/antigen screening assays.
AB  - In a diagnostic laboratory performing analyses for about 40 hospitals and 2,000
      physicians treating outpatients results of HIV 4th generation combined
      antibody/antigen screening assays were monitored over a period of 50 months. In
      period A (Jan 2007 - Mar 2009) 37,986 serum samples were examined by Architect
      and in period B (Apr 2009 - Feb 2011) 38,178 samples by Modular system. In period
      B1 (Apr 2009 - Jun 2010) 24,756 samples were analyzed only by Modular system
      while in period B2 (July 2010 - February 2011) 13,422 samples were examined in
      parallel by Modular and Axsym system. Sensitivity and negative predictive value
      of each was 100%. Specificities ranged from 99.69-99.88% and positive predictive
      values (ppv) from 35.1-65.9%. Architect test results obtained a better
      reliability than Modular test results while Axsym test results were similar to
      that of Architect system. However, specificity and ppv of Modular system was
      markedly improved in period B2. In summary our study shows that long term
      monitoring of HIV combined antibody/antigen screening test results allows
      discovering of impairment and improvement of HIV testing quality. We also show
      that in a low prevalence region specificities of > 99% are accompanied by
      relatively low ppv. Increase of cut off values to define reactivity of the tests
      will increase specificities and ppv without affecting sensitivity.

PMID- 22998236
TI  - HIV progression to AIDS: bioinformatics approach to determining the mechanism of
      action.
AB  - The mechanism by which HIV infection transforms into AIDS disease is unclear.
      Several factors such as the decline in immune response, increase in replication
      rate, Syncytium inducing capacity and ability of the viruses to infect tumour
      cell lines are found to be associated with HIV progression to AIDS. What has not
      been investigated is the role of an increase in affinity for the CD4+ T cells by
      the HIV-1 T cell lymphocyte-loving (T-tropic) viruses. They are known to be
      mutants of the Macrophage-loving (M-tropic) viruses and dominate the late stage
      of the HIV infection in the disease progression. To elucidate the mechanism by
      which HIV is transformed into AIDS, this role is examined by using the Resonant
      Recognition Model (RRM). This is achieved by comparing the degree of affinity
      between the host CD4 and the gp120 from the HIV-1 M-tropic and HIV-1 T-tropic
      viruses as well as the isolates of HIV-2 and Simian immunodeficiency virus (SIV).
      The results reveal that only HIV-1 T-tropic viruses bind effectively to the CD4
      suggesting that T-tropic viruses, which were identified to have mutated from the
      M-tropic viruses, acquire enhanced and long-lasting attachment to the CD4. This
      sustained affinity brings about continued attack on the diminishing CD4 until the
      immune system of the host collapses, which manifests clinically as AIDS. The
      findings therefore suggest an approach that should target the Variable region 3
      (V3) of the HIV-1 gp120 at the early stage of the infection as a part of the
      HIV/AIDS management procedure. This procedure is essential as early initiation of
      HIV/AIDS therapy is generally assumed to prevent the spread of the virus and
      deterioration of the host immunity. The study is expected to help better
      understand the HIV pathogenesis and re-strategise pharmaceutical approaches to
      designing new HIV/AIDS therapeutic interventions.

PMID- 22998237
TI  - Catalytic trimerization of bis-silylated diazomethane.
AB  - (Me(3)Si)(2)CNN isomerizes upon addition of traces of [Me(3)Si](+) ions to give
      (Me(3)Si)(2)NNC, which then undergoes an unusual trimerization reaction to give
      exclusively 4-diazenyl-3-hydrazinylpyrazole. As catalyst the isonitrilium ion,
      [(Me(3)Si)(2)NNC(SiMe(3))](+), was identified and fully characterized.
      Experiments and computations indicate a three-step reaction including
      isomerization of diazomethane, a C-C or N-C coupling, and a formal cycloaddition
      reaction. The kinetics and thermodynamics are discussed on the basis of DFT
      calculations.

PMID- 22998239
TI  - Comparison of high definition oscillometric and Doppler ultrasound devices with
      invasive blood pressure in anaesthetized dogs.
AB  - OBJECTIVE: To use the American College of Veterinary Internal Medicine (ACVIM)
      validation criteria to evaluate the performance of high definition oscillometric
      (HDO) and Doppler blood pressure measurement techniques against invasive blood
      pressure measurements in anaesthetized dogs. STUDY DESIGN: Prospective clinical
      study. ANIMALS: Twenty client-owned dogs. MATERIALS AND METHODS: Invasive blood
      pressure was measured using a catheter inserted into a pedal artery and an
      electronic transducer. The sites of cuff placement for the HDO measurements were
      the mid antebrachium or the proximal tail and, for the Doppler technique, the
      distal tibia. Agreement between invasive and non-invasive blood pressure
      measurements was estimated by the Bland-Altman method. RESULTS: Only 10% and 34%
      of Doppler measurements were within 10 and 20 mmHg of invasive blood pressure
      values, respectively. The Doppler device failed to meet the ACVIM validation
      criteria for blood pressure measurement devices. The best agreement between HDO
      and invasive blood pressure measurement technique was observed for mean arterial
      blood pressure (MAP); 67% and 95% of readings were within 10 and 20 mmHg of
      invasive blood pressure values respectively. In addition, 52% and 87% of
      diastolic arterial blood pressure (DAP) measurements were within 10 and 20 mmHg
      of invasive readings. High definition oscillometric readings did not meet ACVIM
      recommended limits for SAP. CONCLUSION AND CLINICAL RELEVANCE: The Doppler
      technique overestimated and the HDO device showed limited agreement with invasive
      blood pressure measurement in anaesthetized dogs. High definition oscillometry
      met most of the ACVIM requirements for MAP and DAP while the Doppler technique
      did not.

PMID- 22998240
TI  - A current opinion on electrophoretic deposition in pulsed and alternating fields.
AB  - Electrophoretic deposition (EPD) is a colloidal production process developed in
      the early 20th century. Industrial scale EPD for the production of electronic
      components and phosphorescent screens and in the form of cataphoretic painting
      has known some success. Despite its limited practical applications, the inherent
      versatility of EPD has never ceased to fuel research into this technique. One of
      the major drives of this research was to render the method more environmentally
      friendly by enabling deposition from aqueous suspensions. One particular route,
      suggested to circumvent the problems caused by the use of water in EPD, is the
      use of alternating or pulsed fields. Recently, the use of alternating fields in
      EPD has been investigated for the deposition of biological matter in the form of
      cells and molecules. With this new avenue of research opening up and coinciding
      with a rise in biotechnological processes, one can expect a renewed interest in
      traditional EPD and fundamental research on the use of pulsed and alternating
      fields in this technique. Hence, this review attempts to summarize a century's
      worth of both fundamental and applied research for scientists venturing into the
      field of EPD.

PMID- 22998238
TI  - Lamstatin--a novel inhibitor of lymphangiogenesis derived from collagen IV.
AB  - The lymphatic system is essential for the maintenance of tissue homeostasis and
      immunity. Its dysfunction in disease (such as lymphangioleiomyomatosis) can lead
      to chylous effusions, oedema or dissemination of malignant cells. Collagen IV has
      six alpha chains, of which some of the non-collagenous-1 domains have endogenous
      anti-angiogenic properties, however, little is known about specific endogenous
      anti-lymphangiogenic characteristics. In this study we sought to investigate the
      expression levels of collagen IV non-collagenous-1 domains in lung tissue of
      patients with and without lymphangioleiomyomatosis to explore the hypothesis that
      a member of the collagen IV family, specifically the non-collagenous domain-1 of
      alpha5, which we named lamstatin, has anti-lymphangiogenic properties. Levels of
      lamstatin detected by immunohistochemistry were decreased in lungs of
      lymphangioleiomyomatosis patients. We produced recombinant lamstatin in an E.coli
      expression system and synthesized a 17-amino acid peptide from a theoretically
      identified, active region (CP17) and tested their effects in vitro and in vivo.
      Recombinant lamstatin and CP17 inhibited proliferation, migration and cord
      formation of human microvascular lung lymphatic endothelial cells, in vitro.
      Furthermore, lamstatin and CP17 decreased complexity and dysplasia of the tumour
      associated lymphatic network in a lung adenocarcinoma xenograft mouse model. In
      this study we identified a novel, direct inhibitor of lymphangiogenesis, derived
      from collagen IV. This may prove useful for exploring new avenues of treatment
      for lymphangioleiomyomatosis and metastasis via the lymphatic system in general.

PMID- 22998241
TI  - The criteria for metformin-associated lactic acidosis: the quality of reporting
      in a large pharmacovigilance database.
AB  - AIMS: To study the quality of pharmacovigilance reporting in cases of so-called
      'metformin-associated lactic acidosis' and, ultimately, whether or not the
      criteria for this condition are indeed met. METHODS: We searched for cases
      meeting the criteria for metformin-associated lactic acidosis [arterial pH <
      7.35, blood lactate > 5 mmol/l (45 mg/dl) and detectable plasma metformin
      concentration] in a 15-year period (1995-2010) in a pharmacovigilance database of
      the license holder for metformin (Merck Serono, Lyon, France). RESULTS: We found
      869 reports stated as 'metformin-associated lactic acidosis' from 32 countries.
      The respective criteria for pH, lactate concentration and metformin concentration
      were met in 51.2, 53.3 and 13.9% of cases. All three criteria were met in just
      10.4% of cases. By year, each of the percentages remained roughly stable
      throughout the study period. CONCLUSIONS: The role of metformin in triggering
      metformin-associated lactic acidosis was assessed incorrectly in most patients
      and the quality of reporting did not improve over time.

PMID- 22998242
TI  - Communication: Beyond the random phase approximation on the cheap: improved
      correlation energies with the efficient "radial exchange hole" kernel.
AB  - The "ACFD-RPA" correlation energy functional has been widely applied to a variety
      of systems to successfully predict energy differences, and less successfully
      predict absolute correlation energies. Here, we present a parameter-free exchange
      correlation kernel that systematically improves absolute correlation energies,
      while maintaining most of the good numerical properties that make the ACFD-RPA
      numerically tractable. The radial exchange hole kernel is constructed to
      approximate the true exchange kernel via a carefully weighted, easily computable
      radial averaging. Correlation energy errors of atoms with 2-18 electrons show a
      13-fold improvement over the RPA and a threefold improvement over the related
      Petersilka, Gossmann, and Gross kernel, for a mean absolute error of 13 mHa or
      5%. The average error is small compared to all but the most difficult to evaluate
      kernels. van der Waals C(6) coefficients are less well predicted, but still show
      improvements on the RPA, especially for highly polarisable Li and Na.

PMID- 22998243
TI  - Jahn-Teller, pseudo-Jahn-Teller, and spin-orbit coupling Hamiltonian of a d
      electron in an octahedral environment.
AB  - Starting from the model of a single d-electron in an octahedral crystal
      environment, the Hamiltonian for linear and quadratic Jahn-Teller (JT) coupling
      and zeroth order as well as linear spin-orbit (SO) coupling in the (2)T(2g) +
      (2)E(g) electronic multiplet is derived. The SO coupling is described by the
      microscopic Breit-Pauli operator. The 10 * 10 Hamiltonian matrices are explicitly
      given for all linear and quadratic electrostatic couplings and all linear SO
      induced couplings. It is shown that the (2)T(2g) manifold exhibits, in addition
      to the well-known electrostatic JT effects, linear JT couplings which are of
      relativistic origin, that is, they arise from the SO operator. While only the
      e(g) mode is JT-active in the (2)E(g) state in the nonrelativistic approximation,
      the t(2g) mode becomes JT-active through the SO operator. Both electrostatic as
      well as relativistic forces contribute to the (2)T(2g) - (2)E(g) pseudo-JT
      coupling via the t(2g) mode. The relevance of these analytic results for the
      static and dynamic JT effects in octahedral complexes containing heavy elements
      is discussed.

PMID- 22998244
TI  - Molecular gradient for second-order Moller-Plesset perturbation theory using the
      divide-expand-consolidate (DEC) scheme.
AB  - We demonstrate that the divide-expand-consolidate (DEC) scheme--which has
      previously been used to determine the second-order Moller-Plesset (MP2)
      correlation energy--can be applied to evaluate the MP2 molecular gradient in a
      linear-scaling and embarrassingly parallel manner using a set of local Hartree
      Fock orbitals. All manipulations of four-index quantities (describing electron
      correlation effects) are carried out using small local orbital fragment spaces,
      whereas two-index quantities are treated for the full molecular system. The sizes
      of the orbital fragment spaces are determined in a black-box manner to ensure
      that the error in the DEC-MP2 correlation energy compared to a standard MP2
      calculation is proportional to a single input threshold denoted the fragment
      optimization threshold (FOT). The FOT also implicitly controls the error in the
      DEC-MP2 molecular gradient as substantiated by a theoretical analysis and
      numerical results. The development of the DEC-MP2 molecular gradient is the
      initial step towards calculating higher order energy derivatives for large
      molecular systems using the DEC framework, both at the MP2 level of theory and
      for more accurate coupled-cluster methods.

PMID- 22998245
TI  - A fusion of the closed-shell coupled cluster singles and doubles method and
      valence-bond theory for bond breaking.
AB  - Closed-shell coupled cluster singles and doubles (CCSD) is among the most
      important of electronic-structure methods. However, it fails qualitatively when
      applied to molecular systems with more than two strongly correlated electrons,
      such as those with stretched or broken covalent bonds. We show that it is
      possible to modify the doubles amplitudes to obtain a closed-shell CCSD method
      that retains the computational cost and desirable features of standard closed
      shell CCSD, e.g., correct spin symmetry, size extensivity, orbital invariance,
      etc., but produces greatly improved energies upon bond dissociation of multiple
      electron pairs; indeed, under certain conditions the dissociation energies are
      exact.

PMID- 22998247
TI  - Assessment of ten DFT methods in predicting structures of sheet silicates:
      importance of dispersion corrections.
AB  - The performance of ten density functional theory (DFT) methods in a prediction of
      the structure of four clay minerals, in which non-bonding interactions dominate
      in the layer stacking (dispersive forces in talc and pyrophyllite, and hydrogen
      bonds in lizardite and kaolinite), is reported. In a set of DFT methods following
      functionals were included: standard local and semi-local (LDA, PW91, PBE, and
      RPBE), dispersion corrected (PW91-D2, PBE-D2, RPBE-D2, and vdW-TS), and
      functionals developed specifically for solids and solid surfaces (PBEsol and
      AM05). We have shown that the standard DFT functionals fail in the correct
      prediction of the structural parameters, for which non-bonding interactions are
      important. The remarkable improvement leading to very good agreement with
      experimental structures is achieved if the dispersion corrections are included in
      the DFT calculations. In such cases the relative error for the most sensitive
      lattice vector c dropped below 1%. Very good performance was also observed for
      both DFT functionals developed for solids. Especially, the results achieved with
      the PBEsol are qualitatively similar to those with DFT-D2.

PMID- 22998246
TI  - Comparison of the performance of exact-exchange-based density functional methods.
AB  - How to describe nondynamic electron correlation is still a major challenge to
      density functional theory (DFT). Recent models designed particularly for this
      problem, such as Becke'05 (B05) and Perdew-Staroverov-Tao-Scuseria (PSTS)
      functionals employ the exact-exchange density, the efficient calculation of which
      is technically quite challenging. We have recently implemented self-consistently
      the B05 functional based on an efficient resolution-identity (RI) technique. In
      this study, we report a self-consistent RI implementation of the PSTS functional.
      In contrast to its original implementation, our version brings no limitation on
      the choice of the basis set. We have also implemented the Mori-Sanchez-Cohen-Yang
      2 (MCY2) functional, another recent DFT method that includes full exact exchange.
      The performance of PSTS, B05, and MCY2 is validated on thermochemistry, reaction
      barriers, and dissociation energy curves, with an emphasis on nondynamic
      correlation effects in the discussion. All three methods perform rather well in
      general, B05 and MCY2 being on average somewhat better than PSTS. We include also
      results with other functionals that represent various aspects of the development
      in this field in recent years, including B3LYP, M06-HF, M06-2X, omegaB97X, and
      TPSSh. The performance of the heavy-parameterized functionals M06-2X and
      omegaB97X is on average better than that of B05, MCY2, and PSTS for standard
      thermodynamic properties and reactions, while the latter functionals do better in
      hydrogen abstraction reactions and dissociation processes. In particular, B05 is
      found to be the only functional that yields qualitatively correct dissociation
      curves for two-center symmetric radicals like He(2)(+). Finally, we compare the
      performance of all these functionals on a strongly correlated exemplary case
      system, the NO dimer. Only PSTS, B05, and MCY2 describe the system qualitatively
      correctly. Overall, this new type of functionals show good promise of overcoming
      some of the difficulties DFT encounters for systems with strong nondynamic
      correlation.

PMID- 22998248
TI  - Analysis of the physical contributions to magnetic couplings in broken symmetry
      density functional theory approach.
AB  - We present a new and simple scheme that aims to decompose into its main physical
      contributions the magnetic exchange interaction between two unpaired electrons.
      It is based on the popular broken-symmetry density functional theory (DFT)
      approach and relies on the frozen orbital capabilities of the local self
      consistent field method. Accordingly, the magnetic exchange interaction energy
      can be separated into three main contributions: the direct exchange between
      magnetic orbitals, the spin polarization of the core orbitals, and the relaxation
      of the magnetic orbitals (kinetic exchange). This decomposition scheme is applied
      to a series of binuclear inorganic magnetic compounds both ferromagnetic and
      antiferromagnetic. The direct exchange is determined from the restricted DFT
      description. On the one hand, starting from the restricted orbital set and
      relaxing only the magnetic orbitals provides the kinetic exchange contribution
      and an estimate of the t and U parameters of the generalized Anderson mechanism.
      On the other hand, relaxing the core orbitals only introduces the spin
      polarization contribution. The decomposition leads to almost additive
      contributions. The effect of the amount of Hartree-Fock exchange on the different
      contributions is analyzed.

PMID- 22998249
TI  - Magnetic coupling constants and vibrational frequencies by extended broken
      symmetry approach with hybrid functionals.
AB  - The description of the electronic structure and magnetic properties of multi
      centers transition metal complexes, especially of mixed-valence compounds, still
      represents a challenge for density functional theory (DFT) methods. The energies
      and the geometries of the correctly symmetrized low-spin ground state are
      estimated using the Heisenberg-Dirac-van Vleck spin Hamiltonian within the
      extended broken symmetry method introduced by Marx and co-workers [Nair et al.,
      J. Chem. Theory Comput. 4, 1174-1188 (2008)]. In the present work we extend the
      application of this technique, originally implemented using the DFT+U scheme, to
      the use of hybrid functionals, investigating the ground-state properties of di
      iron and di-manganese compounds. The calculated magnetic coupling and vibrational
      properties of ferredoxin molecular models are in good agreements with
      experimental results and DFT+U calculations. Six different mixed-valence Mn(III)
      Mn(IV) compounds have been extensively studied optimizing the geometry in low
      spin, high-spin, and broken-symmetry states and with different functionals. The
      magnetic coupling constants calculated by the extended broken symmetry approach
      using B3LYP functional presents a remarkable agreement with the experimental
      results, revealing that the proposed methodology provides a consistent and
      accurate DFT approach to the electronic structure of multi-centers transition
      metal complexes.

PMID- 22998250
TI  - Vibrational multi-reference coupled cluster theory in bosonic representation.
AB  - The vibrational multi-reference coupled cluster method is developed to calculate
      the vibrational excitation energies of polyatomic molecules. The method is
      implemented on ozone and formaldehyde molecules and the results are compared with
      full vibrational configuration interaction (FVCI) method. A good agreement is
      found between the vibrational multi-reference coupled cluster method and
      converged FVCI method for lower lying vibrational states.

PMID- 22998251
TI  - The virial theorem for the smoothly and sharply, penetrably and impenetrably
      confined hydrogen atom.
AB  - Confinement of atoms by finite or infinite boxes containing sharp (discontinuous)
      jumps has been studied since the fourth decade of the previous century, modelling
      the effect of external pressure. Smooth (continuous) counterparts of such
      confining potentials, that depend on a parameter such that in an appropriate
      limit they coincide with the sharp confining potentials, are investigated, with
      an emphasis on deriving the corresponding virial and Hellmann-Feynman theorems.

PMID- 22998252
TI  - Efficient computation of adiabatic electronic populations in multi-mode vibronic
      systems: theory, implementation, and application.
AB  - The effective-mode formalism developed earlier is applied to efficiently compute
      adiabatic electronic populations of multi-mode vibronic systems. Two different
      versions of the formalism are utilized. In the first one, the effective modes are
      used as new vibrational basis, and the time-dependent wave function as well as
      populations are calculated numerically exactly. In the second variant, the
      hierarchy-of-modes formalism is applied as an approximation scheme which leads to
      accurate results when including typically 7-10 members of the hierarchy. While in
      the first version, the propagation of the wave packet becomes numerically
      tedious, the computation of the adiabatic populations is rendered possible at
      all. Through the hierarchy-of-modes formalism, both the propagation as well as
      computation of adiabatic populations are speeded up by 1-3 orders of magnitude in
      typical cases. The formalism is applied to study the dynamics of pyrazine-type
      models for varying vibronic coupling strength and a (very) large number of bath
      modes.

PMID- 22998253
TI  - Van der Waals interactions between hydrocarbon molecules and zeolites: periodic
      calculations at different levels of theory, from density functional theory to the
      random phase approximation and Moller-Plesset perturbation theory.
AB  - The adsorption of small alkane molecules in purely siliceous and protonated
      chabazite has been investigated at different levels of theory: (i) density
      functional (DFT) calculations with a gradient-corrected exchange-correlation
      functional; DFT calculations using the Perdew-Burke-Ernzerhof (PBE) functional
      with corrections for the missing dispersion forces in the form of C(6)/R(6) pair
      potentials with (ii) C(6) parameters and vdW radii determined by fitting accurate
      energies for a large molecular data base (PBE-d) or (iii) derived from "atoms in
      a solid" calculations; (iv) DFT calculations using a non-local correlation
      functional constructed such as to account for dispersion forces (vdW-DF); (v)
      calculations based on the random phase approximation (RPA) combined with the
      adiabatic-coupling fluctuation-dissipation theorem; and (vi) using Hartree-Fock
      (HF) calculations together with correlation energies calculated using second
      order Moller-Plesset (MP2) perturbation theory. All calculations have been
      performed for periodic models of the zeolite and using a plane-wave basis and the
      projector-augmented wave method. The simpler and computationally less demanding
      approaches (i)-(iv) permit a calculation of the forces acting on the atoms using
      the Hellmann-Feynman theorem and further a structural optimization of the
      adsorbate-zeolite complex, while RPA and MP2 calculations can be performed only
      for a fixed geometry optimized at a lower level of theory. The influence of
      elevated temperature has been taken into account by averaging the adsorption
      energies calculated for purely siliceous and protonated chabazite, with weighting
      factors determined by molecular dynamics calculations with dispersion-corrected
      forces from DFT. Compared to experiment, the RPA underestimates the adsorption
      energies by about 5 kJ/mol while MP2 leads to an overestimation by about 6 kJ/Mol
      (averaged over methane, ethane, and propane). The most accurate results have been
      found for the "hybrid" RPA-HF method with an average error of less than 2 kJ/mol
      only, while RPA underestimates the adsorption energies by about 8 kJ/mol on
      average. MP2 overestimates the adsorption energies slightly, with an average
      error of 5 kJ/mol. The more approximate and computationally less demanding
      methods such as the vdW-DF density functional or the C(6)/R(6) pair potentials
      with C(6) parameters from "atoms in a solid" calculations overestimate the
      adsorption energies quite strongly. Relatively good agreement with experiment is
      achieved with the empirical PBE+d method with an average error of about 5 kJ/mol.

PMID- 22998254
TI  - Variational fractional-spin density-functional theory for diradicals.
AB  - Accurate computation of singlet-triplet energy gaps of diradicals remains a
      challenging problem in density-functional theory (DFT). In this work, we propose
      a variational extension of our previous work [D. H. Ess, E. R. Johnson, X. Q. Hu,
      and W. T. Yang, J. Phys. Chem. A 115, 76 (2011)], which applied fractional-spin
      density-functional theory (FS-DFT) to diradicals. The original FS-DFT approach
      assumed equal spin-orbital occupancies of 0.5 alpha-spin and 0.5 beta-spin for
      the two degenerate, or nearly degenerate, frontier orbitals. In contrast, the
      variational approach (VFS-DFT) optimizes the total energy of a singlet diradical
      with respect to the frontier-orbital occupation numbers, based on a full
      configuration-interaction picture. It is found that the optimal occupation
      numbers are exactly 0.5 alpha-spin and 0.5 beta-spin for diradicals such as O(2),
      where the frontier orbitals belong to the same multidimensional irreducible
      representation, and VFS-DFT reduces to FS-DFT for these cases. However, for
      diradicals where the frontier orbitals do not belong to the same irreducible
      representation, the optimal occupation numbers can vary between 0 and 1.
      Furthermore, analysis of CH(2) by VFS-DFT and FS-DFT captures the (1)A(1) and
      (1)B(1) states, respectively. Finally, because of the static correlation error in
      commonly used density functional approximations, both VFS-DFT and FS-DFT
      calculations significantly overestimate the singlet-triplet energy gaps for
      disjoint diradicals, such as cyclobutadiene, in which the frontier orbitals are
      confined to separate atomic centers.

PMID- 22998255
TI  - High resolution 11B NMR of magnesium diboride using cryogenic magic angle
      spinning.
AB  - Static and magic-angle spinning (11)B nuclear magnetic resonance (NMR) data at
      4.7 T and 8.5 T have been obtained under cryogenic conditions on a diluted sample
      of magnesium diboride powder in the normal and superconducting state. The data
      provide accurate information on the magnetic shift and longitudinal relaxation
      time down to a temperature of 8 K, with a resolution improvement over the entire
      temperature range. The onset of superconductivity is unaffected by the sample
      rotation, as revealed by a steep variation of the magnetic shift just below the
      critical temperature.

PMID- 22998256
TI  - Vibrational effects on valence electron momentum distributions of ethylene.
AB  - We report an electron momentum spectroscopy study of vibrational effects on the
      electron momentum distributions for the outer valence orbitals of ethylene
      (C(2)H(4)). The symmetric noncoplanar (e,2e) experiment has been conducted at an
      impact energy of 1.2 keV. Furthermore, a theoretical method of calculating
      electron momentum distributions for polyatomic molecules has been developed with
      vibrational effects being involved. It is shown from comparisons between
      experiment and theory that taking into account effects of the CH(2) asymmetric
      stretching and CH(2) rocking vibrational modes of C(2)H(4) is essential for a
      proper understanding of the electron momentum distribution of the 1b(3g)
      molecular orbital.

PMID- 22998257
TI  - Optical absorption spectra of gold clusters Au(n) (n = 4, 6, 8,12, 20) from long
      range corrected functionals with optimal tuning.
AB  - Absorption UV spectra of gold clusters Au(n) (n = 4, 6, 8, 12, 20) are
      investigated using the time-dependent density functional theory (TDDFT). The
      calculations employ several long-range corrected xc functionals: omegaB97X, LC
      omegaPBEh, CAM-B3LYP* (where * denotes a variant with corrected asymptote of CAM
      B3LYP), and LC-omegaPBE. The latter two are subject to first-principle tuning
      according to a prescription of Stein et al. [Phys. Rev. Lett. 105, 266802 (2010)]
      by varying the range separation parameter. TDDFT results are validated for Au(4)
      and Au(8) against the equation-of-motion coupled cluster singles and doubles
      results and the experiment. Both long-range correction and the inclusion of a
      fixed portion of the exact exchange in the short-range are essential for the
      proper description of the optical spectra of gold. The omegaB97X functional
      performs well across all studied cluster sizes. LC-omegaPBEh, with parameters
      recommended by Rohrdanz et al. [J. Chem. Phys. 130, 054112 (2009)], affords the
      best performance for clusters of n > 4. The optimally tuned CAM-B3LYP* features
      the range separation parameter of 0.33 for Au(4) and 0.25 for all the larger
      clusters. For LC-omegaPBE the tuning procedure resulted in incorrect transition
      energies and oscillator strengths despite the fact that the optimized functional
      showed the accurate linear dependence on fractional electron numbers. Au(n) (n =
      4, 6, 8) feature optical gaps above of 3 eV and Au(20) of ~2.9 eV. In Au(12) this
      gap narrows to ~2.1 eV. The calculated spectrum for Au(20) involves intensity
      being concentrated in only a few transitions with the absorption maximum at 3.5
      eV. The intense 3.5 eV absorption is present in all cluster sizes of n > 4. The
      calculated HOMO-LUMO gaps for all cluster sizes are within 0.5 eV of the
      difference between the vertical ionization potential and electron affinity. The
      reasons for this and for the failure of conventional xc functionals for optical
      spectra of gold are discussed.

PMID- 22998258
TI  - Experimental and theoretical studies of the decomposition of new imidazole based
      energetic materials: model systems.
AB  - Decomposition of three imidazole based model energetic systems (2-nitroimidazole,
      4-nitroimidazole, and 1-methyl-5-nitroimidazole) is investigated both
      experimentally and theoretically. The initial decomposition mechanism for these
      three nitroimidazoles is explored with nanosecond energy resolved spectroscopy,
      and quantum chemical theory at the complete active space self-consistent field
      (CASSCF) level. The NO molecule is observed as an initial decomposition product
      from these three nitroimidazoles subsequent to UV excitation. A unique,
      excitation wavelength independent dissociation channel is observed for these
      three nitroimidazoles that generates the NO product with a rotationally cold (~50
      K) and a vibrationally mildly hot (~800 K) distribution. Potential energy surface
      calculations at the CASSCF/6-31G(d) level of theory illustrate that conical
      intersections play an important and essential role in the decomposition
      mechanism. Electronically excited S(2) nitroimidazole molecules relax to the S(1)
      state through the (S(2)/S(1))(CI) conical intersection, and undergo a nitro
      nitrite isomerization to generate the NO product from the S(1) potential energy
      surface. Nevertheless, NO(2) elimination and nitro-nitrite isomerization are
      expected to be competitive reaction mechanisms for the decomposition of these
      molecules on the ground state potential energy surface from the Franck-Condon
      equilibrium geometry through thermal dissociation.

PMID- 22998259
TI  - Ab initio rovibrational structure of the lowest singlet state of O2-O2.
AB  - Rovibrational bound states of the O(2)((3)Sigma(g)(-), v = 0)-O(2)((3)Sigma(g)(
      ), v = 0) dimer in its singlet electronic state have been obtained by solving the
      time-independent Schrodinger equation for the nuclear degrees of freedom. We have
      employed two different ab initio potential energy surfaces, based on high level
      multiconfigurational methods, which are expected to give upper and lower bounds
      for the real values of the interaction. Results are compared with spectroscopy
      experiments as well as with calculations using other semi ab initio and empirical
      interaction potentials. For the two ab initio potentials studied here, the ground
      vibrational state has a rectangular geometry and behaves as a semi-rigid
      molecule. The associated rotational constant is found in very good agreement with
      high resolution spectra. However, the computed dissociation energy and the
      frequency of the torsion mode are larger than previous experimental
      determinations, and possible reasons for these discrepancies are discussed. On
      the other hand, we have computed the splitting between the rovibrational states
      of the singlet and triplet electronic states and have found a fair agreement with
      measurements of the dimer spectra in a solid rare gas host.

PMID- 22998260
TI  - Ab initio long-range interaction and adiabatic channel capture model for
      ultracold reactions between the KRb molecules.
AB  - The coefficients at the lowest-order electrostatic, induction, and dispersion
      terms of the anisotropic long-range potential between the two KRb((1)Sigma(+))
      molecules are evaluated through the static and dynamic molecular properties using
      the ab initio coupled cluster techniques. Adiabatic channel potentials for the
      ground-state molecules are obtained and used for the numerical quantum capture
      probability calculations in the spirit of the statistical adiabatic channel
      models. Capture rate coefficients for indistinguishable (polarized) and
      distinguishable (unpolarized) molecules at temperatures below 10 MUK agree well
      with those computed with the simple isotropic dispersion R(-6) potential, but
      underestimate the measured ones [Ospelkaus et al., Science 327, 853 (2010)] up to
      a factor of 3. Preliminary assessment of the effects of higher-order long-range
      terms, retardation of dispersion forces, and magnetic dipole-dipole interaction
      does not offer any clear perspectives for drastic improvement of the capture
      approximation for the reactions studied.

PMID- 22998261
TI  - Fine and hyperfine excitation of NH and ND by He: on the importance of
      calculating rate coefficients of isotopologues.
AB  - The NH and ND molecules play an important role in interstellar nitrogen
      chemistry. Accurate modeling of their abundance in space requires the calculation
      of rates for collisional excitation by the most abundant interstellar species. We
      calculate rate coefficients for the fine and hyperfine excitation of NH and ND by
      He. State-to-state rate coefficients between the first levels of NH and ND were
      obtained for temperatures ranging from 5 to 150 K. Fine structure resolved rate
      coefficients present a strong propensity rule in favor of Deltaj = DeltaN
      transitions, as expected from theoretical considerations. The Deltaj = DeltaF(1)
      = DeltaF propensity rule is observed for the hyperfine transitions of both
      isotopologues. The two sets of fine structure resolved rate coefficients are
      compared in detail and we find significant differences between the two
      isotopologues. This comparison shows that specific calculations are necessary for
      the deuterated isotopologues of any hydride. The new rate coefficients will help
      significantly in the interpretation of NH and ND terahertz spectra observed with
      current and future telescopes, and enable these molecules to become a powerful
      astrophysical tool for studying the nitrogen chemistry.

PMID- 22998262
TI  - Vibrational solvatochromism and electrochromism. II. Multipole analysis.
AB  - Small infrared probe molecules have been widely used to study local electrostatic
      environment in solutions and proteins. Using a variety of time- and frequency
      resolved vibrational spectroscopic methods, one can accurately measure the
      solvation-induced vibrational frequency shifts and the timescales and amplitudes
      of frequency fluctuations of such IR probes. Since the corresponding frequency
      shifts are directly related to the local electric field and its spatial
      derivatives of the surrounding solvent molecules or amino acids in proteins, one
      can extract information on local electric field around an IR probe directly from
      the vibrational spectroscopic results. Here, we show that, carrying out a
      multipole analysis of the solvatochromic frequency shift, the solvatochromic
      dipole contribution to the frequency shift is not always the dominant factor. In
      the cases of the nitrile-, thiocyanato-, and azido-derivatized molecules, the
      solvatochromic quadrupole contributions to the corresponding stretch mode
      frequency shifts are particularly large and often comparable to the
      solvatochromic dipole contributions. Noting that the higher multipole moment
      solvent electric field interactions are short range effects in comparison to the
      dipole interaction, the H-bonding interaction-induced vibrational frequency shift
      can be caused by such short-range multipole-field interaction effects. We
      anticipate that the present multipole analysis method specifically developed to
      describe the solvatochromic vibrational frequency shifts will be useful to
      understand the intermolecular interaction-induced vibrational property changes
      and to find out a relationship between vibrational solvatochromism and
      electrochromism of IR probes in condensed phases.

PMID- 22998263
TI  - CCSD(T) potential energy and induced dipole surfaces for N2-H2(D2): retrieval of
      the collision-induced absorption integrated intensities in the regions of the
      fundamental and first overtone vibrational transitions.
AB  - The present work aims at ab initio characterization of the integrated intensity
      temperature variation of collision-induced absorption (CIA) in N(2)-H(2)(D(2)).
      Global fits of potential energy surface (PES) and induced dipole moment surface
      (IDS) were made on the basis of CCSD(T) (coupled cluster with single and double
      and perturbative triple excitations) calculations with aug-cc-pV(T,Q)Z basis
      sets. Basis set superposition error correction and extrapolation to complete
      basis set (CBS) limit techniques were applied to both energy and dipole moment.
      Classical second cross virial coefficient calculations accounting for the first
      quantum correction were employed to prove the quality of the obtained PES. The
      CIA temperature dependence was found in satisfactory agreement with available
      experimental data.

PMID- 22998264
TI  - Wave packet calculations on nonadiabatic effects for the O(3P)+HF(1Sigma+)
      reaction under hyperthermal conditions.
AB  - We present wave packet calculations of total and state-to-state reaction
      probabilities and integral cross sections for the nonadiabatic dynamics of the
      O((3)P)+HF -> F((2)P)+OH((2)Pi) reaction at hyperthermal collision energies
      ranging from 1.2 to 2.4 eV. The validity of the centrifugal sudden approximation
      is discussed for the title reaction and a comprehensive investigation of the
      influence of nonadiabatic effects on the dynamics of this reactive system at high
      (hyperthermal) collision energies is presented. In general, nonadiabatic effects
      are negligible for averaged observables, such as total reaction probabilities and
      integral cross sections, but they are clearly observed in detailed observables
      such as rotationally state-resolved reaction probabilities. A critical discussion
      of nonadiabatic effects on the dynamics of the title reaction is carried out by
      comparing with the reverse reaction and the characteristics of the adiabatic and
      diabatic potential energy surfaces involved.

PMID- 22998265
TI  - Ultrafast solvation response in room temperature ionic liquids: possible origin
      and importance of the collective and the nearest neighbour solvent modes.
AB  - Recent three-pulse photon echo peak shift (3PEPS) measurements [M. Muramatsu, Y.
      Nagasawa, and H. Miyasaka, J. Phys. Chem. A 115, 3886 (2011)] with several room
      temperature ionic liquids (RTILs) have revealed multi-exponential dynamics with
      ultrafast solvation timescale in the range, 20 < tau(1)/fs < 250, for both
      imidazolium and phosphonium RTILs. This is striking for two reasons: (i) the
      timescale is much faster than those reported by the dynamic Stokes shift (DSS)
      experiments [S. Arzhantsev, H. Jin, G. A. Baker, and M. Maroncelli, J. Phys.
      Chem. B 111, 4978 (2007)] and (ii) sub-hundered femtosecond solvation response in
      phosphonium ionic liquids is reported for the first time. Here, we present a mode
      coupling theory based calculation where such ultrafast solvation in 3PEPS
      measurements has been visualized to originate from the nearest neighbour solute
      solvent interaction. Consideration of Lennard-Jones interaction for the nearest
      neighbour solute-solvent non-dipolar interaction leads to biphasic dynamics with
      a predicted ultrafast time constant in the ~100-250 fs range, followed by a
      slower one similar to that reported by the 3PEPS measurements. In addition, the
      calculated fast time constants and amplitudes are found to be in general
      agreement with those from computer simulations. Different microscopic mechanisms
      for ultrafast solvation response measured by the 3PEPS and DSS experiments have
      been proposed and relative contributions of the collective and nearest neighbour
      solvent modes investigated. Relation between the single particle rotation and
      ultrafast polar solvation in these RTILs has been explored. Our analyses suggest
      3PEPS and DSS experiments are probably sensitive to different components of the
      total solvation energy relaxation of a laser-excited dye in a given ionic liquid.
      Several predictions have also been made, which may be re-examined via suitable
      experiments.

PMID- 22998266
TI  - Rotational dynamics of a dipolar supercooled liquid.
AB  - We study the rotational dynamics of a supercooled molecular liquid by means of
      molecular dynamics simulations. The system under investigation is composed of
      rigid diatomic molecules with an associate dipole moment. At room temperature,
      orientational correlations decrease rapidly with increasing distances. Upon
      cooling, angles between dipole moments of molecules within the first coordination
      shell decrease. As for the dynamical properties, rotational diffusion
      coefficients decrease with temperature at a smaller rate than translational
      diffusion coefficients do, and the critical temperature associated with the
      former is lower than the one corresponding to their translational counterparts.
      Translation and rotation about an inertial axis are uncorrelated, whereas some
      coupling between translation and dipole reorientation is obtained.

PMID- 22998267
TI  - Effect of trimethylamine-N-oxide on pressure-induced dissolution of hydrophobic
      solute.
AB  - Molecular dynamics simulations are performed to study the effects of increasing
      trimethylamine-N-oxide (TMAO) concentration on the pressure-induced dissolution
      of hydrophobic solutes immersed in water. Such systems are of interest mainly
      because pressure increases the dissolution of hydrophobic protein interior
      causing protein denaturation and TMAO acts to offset the protein denaturing
      effect of high hydrostatic pressures. In view of this, in this study, methane
      molecules are considered as model hydrophobic molecules and simulations are
      performed for four independent TMAO solutions each at four different pressures
      ranging from 2 to 8 kbar. From potentials of mean force calculations, it is found
      that application of pressure reduces the free energy difference between contact
      minimum (CM) and solvent-separated (SSM) minimum of hydrophobic solute,
      suggesting dissolution at high pressures. TMAO, on the other hand, increases the
      relative stability of CM state of methane molecules relative to its SSM state.
      High packing efficiency of water molecules around the hydrophobic solute at high
      pressure is observed. Also observed are TMAO-induced enhancement of water
      structure and direct hydrogen-bonding interaction between TMAO and water and the
      correlated dehydration of hydrophobic solute. From hydrogen bond properties and
      dynamics calculations, it is observed that pressure increases average number of
      water-water hydrogen bonds while reduces their life-times. In contrast, TMAO
      reduces water-water hydrogen bonding but enhances their life-times. These results
      suggest that TMAO can reduce water penetration into the protein interior by
      enhancing water structure and also forming hydrogen bonds with water and hence
      counteracts protein unfolding.

PMID- 22998268
TI  - Structure and short-time dynamics in concentrated suspensions of charged
      colloids.
AB  - We report a comprehensive joint experimental-theoretical study of the equilibrium
      pair-structure and short-time diffusion in aqueous suspensions of highly charged
      poly-acrylate (PA) spheres in the colloidal fluid phase. Low-polydispersity PA
      sphere systems with two different hard-core radii, R(0) = 542 and 1117 A, are
      explored over a wide range of concentrations and salinities using static and
      dynamic light scattering (DLS), small angle x-ray scattering, and x-ray photon
      correlation spectroscopy (XPCS). The measured static and dynamic scattering
      functions are analyzed using state-of-the-art theoretical methods. For all
      samples, the measured static structure factor, S(Q), is in good agreement with
      results by an analytical integral equation method for particles interacting by a
      repulsive screened Coulomb plus hard-core pair potential. In our DLS and XPCS
      measurements, we have determined the short-time diffusion function D(Q) = D(0)
      H(Q)/S(Q), comprising the free diffusion coefficient D(0) and the hydrodynamic
      function H(Q). The latter is calculated analytically using a self-part corrected
      version of the deltagamma-scheme by Beenakker and Mazur which accounts
      approximately for many-body hydrodynamic interactions (HIs). Except for low
      salinity systems at the highest investigated volume fraction phi ~ 0.32, the
      theoretical predictions for H(Q) are in excellent agreement with the experimental
      data. In particular, the increase in the collective diffusion coefficient D(c) =
      D(Q -> 0), and the decrease of the self-diffusion coefficient, D(s) = D(Q ->
      infinity), with increasing phi is well described. In accord with the theoretical
      prediction, the peak value, H(Q(m)), of H(Q) relates to the nearest neighbor cage
      size ~2pi/Q(m), for which concentration scaling relations are discussed. The peak
      values H(Q(m)) are globally bound from below by the corresponding neutral hard
      spheres peak values, and from above by the limiting peak values for low-salinity
      charge-stabilized systems. HIs usually slow short-time diffusion on colloidal
      length scales, except for the cage diffusion coefficient, D(cge) = D(Q(m)), in
      dilute low-salinity systems where a speed up of the system dynamics and
      corresponding peak values of H(Q(m)) > 1 are observed experimentally and
      theoretically.

PMID- 22998269
TI  - New simulation approach using classical formalism to water nuclear magnetic
      relaxation dispersions in presence of superparamagnetic particles used as MRI
      contrast agents.
AB  - Superparamagnetic nanoparticles are used as negative contrast agents in magnetic
      resonance imaging: owing to their large magnetic moment the water proton spins
      are dephased, which accelerates the nuclear magnetic relaxation of an aqueous
      sample containing these particles. Transverse and longitudinal relaxation times
      depend on several parameters of the nanoparticles such as radius and
      magnetization and on experimental parameters such as the static magnetic field or
      echo time. In this work, we introduce a new simulation methodology, using a
      classical formalism, allowing the simulation of the NMR signal during transverse
      and longitudinal relaxation induced by superparamagnetic particles in an aqueous
      solution, which, to our knowledge has never been done before. Nuclear magnetic
      relaxation dispersion profiles are obtained for a wide range of nanoparticle
      radii and magnetizations. The results can be classified in two regimes--the well
      known motional averaging and static regimes. This generalizes previous studies
      focusing on transverse relaxation at high magnetic field (larger than 1 T).
      Simulation results correspond to analytical theories in their validity range and
      so far unknown dependences of the relaxation with magnetization and radii of the
      NMR dispersions profiles are observed, which could be used to characterize
      experimental samples containing large superparamagnetic particles.

PMID- 22998270
TI  - Ultrafast spherulitic crystal growth as a stress-induced phenomenon specific of
      fragile glass-formers.
AB  - We propose a model for the abrupt emergence, below temperatures close to the
      glass transition, of the ultrafast (glass-to-crystal) steady mode of spherulitic
      crystal growth in deeply undercooled liquids. We interpret this phenomenon as
      controlled by the interplay between the generation of stresses by crystallization
      and their partial release by flow in the surrounding amorphous visco-elastic
      matrix. Our model is consistent with both the observed ratios (~10(4)) of fast-to
      slow velocities and the fact that fast growth emerges close to the glass
      transition. It leads us to conclude that the existence of a fast growth regime
      requires both (i) a high fragility of the glassformer; (ii) the fine sub
      structure specific of spherulites. It finally predicts that the transition is
      hysteretic, thus allowing for an independent experimental test.

PMID- 22998271
TI  - Self-diffusion and activity coefficients of ions in charged disordered media.
AB  - Self-diffusion and single ion activity coefficients of ions of size symmetric
      electrolytes were studied in the presence of a collection of charged obstacles
      (called matrix) within a "soft" version of the primitive model of electrolyte
      solutions. The matrix subsystem possesses a net charge, depending on the
      concentration and charge of obstacles. The brownian dynamics method was used to
      calculate the self-diffusion coefficients of mobile species. The replica Ornstein
      Zernike theory for the partly quenched systems was used to calculate the
      individual activity coefficients of mobile ionic species. The results reflect the
      competition between attractive (obstacle-counterion, co-ion-counterion), and
      repulsive (obstacle-co-ion) interactions in these model systems. For the simplest
      possible system of symmetric monovalent ions the latter effect wins: Co-ions are
      excluded from the area around obstacles, and this slows down their diffusion
      compared to that of counterions. Introduction of divalent charges into the system
      changes this result when the concentration of obstacles is low. We compare these
      results to those obtained for the corresponding fully annealed systems, i.e.,
      where all the species are mobile. In most cases the self-diffusion and activity
      coefficients of counterions and co-ions in the presence of charged obstacles
      follow the trends of the fully annealed solution, which are dictated by the
      composition of the mixture. In few situations, however, the presence of charged
      obstacles modifies these trends. Our study allows us to clearly identify the
      effects due to obstacles, and to separate them from those arising from the
      composition of the solution. In the case of charge and size symmetric systems,
      the results for the individual activity coefficients fully support the hypothesis
      of the "electrostatic excluded volume". Thermodynamic and dynamic results are
      consistent in explaining the behavior of the systems studied.

PMID- 22998272
TI  - Comprehensive studies of the electronic structure of pristine and potassium doped
      chrysene investigated by electron energy-loss spectroscopy.
AB  - We have performed electron energy-loss spectroscopy studies in order to
      investigate the electronic properties of chrysene molecular solids. The valence
      band electronic excitation spectra and the C 1s core level excitations have been
      measured for pristine and potassium doped chrysene. The core level studies show a
      fine structure which signals the presence of four close lying conduction bands
      close to the Fermi level. Upon potassium doping, these bands are filled with
      electrons, and we have reached a doping level of about K(2.7)chrysene.
      Furthermore, undoped chrysene is characterized by an optical gap of about 3.3 eV
      and five, relatively weak, excitonic features following the excitation onset.
      Doping induces major changes in the electronic excitation spectra, with a new,
      prominent low energy excitation at about 1.3 eV. The results of a Kramers-Kronig
      analysis indicate that this new feature can be assigned to a charge carrier
      plasmon in the doped material, and momentum dependent studies reveal a negative
      plasmon dispersion.

PMID- 22998273
TI  - Hydration properties of small hydrophobic molecules by Brillouin light
      scattering.
AB  - We study the relaxation of water molecules next to hydrophobic solutes with
      different functional groups by Brillouin light scattering. Evidence is given for
      (i) water activation energy in trimethylamine-N-oxide, proline and t-butyl
      alcohol diluted solutions which is comparable to that of neat water, almost
      independent from solute mole fraction and (ii) moderate slowdown of relaxation
      time of proximal water compared to the bulk, which is consistent with excluded
      volume models. Assuming that the main contribution to viscosity comes from bulk
      and hydration water, a rationale is given of the phenomenological Arrhenius' laws
      for the viscosity of diluted aqueous solutions.

PMID- 22998274
TI  - Dynamics of two-dimensional monolayer water confined in hydrophobic and charged
      environments.
AB  - We perform molecular dynamics simulations to study the effect of charged surfaces
      on the intermediate and long time dynamics of water in nanoconfinements. Here, we
      use the transferable interaction potential with five points (TIP5P) model of a
      water molecule confined in both hydrophobic and charged surfaces. For a single
      molecular layer of water between the surfaces, we find that the temperature
      dependence of the lateral diffusion constant of water up to very high
      temperatures remains Arrhenius with a high activation energy. In case of charged
      surfaces, however, the dynamics of water in the intermediate time regime is
      drastically modified presumably due to the transient coupling of dipoles of water
      molecules with electric field fluctuations induced by charges on the confining
      surfaces. Specifically, the lateral mean square displacements display a distinct
      super-diffusive behavior at intermediate time scale, defined as the time scale
      between ballistic and diffusive regimes. This change in the intermediate time
      scale dynamics in the charged confinement leads to the enhancement of long-time
      dynamics as reflected in increasing diffusion constant. We introduce a simple
      model for a possible explanation of the super-diffusive behavior and find it to
      be in good agreement with our simulation results. Furthermore, we find that
      confinement and the surface polarity enhance the low frequency vibration in
      confinement compared to bulk water. By introducing a new effective length scale
      of coupling between translational and orientational motions, we find that the
      length scale increases with the increasing strength of the surface polarity.
      Further, we calculate the correlation between the diffusion constant and the
      excess entropy and find a disordering effect of polar surfaces on the structure
      of water. Finally, we find that the empirical relation between the diffusion
      constant and the excess entropy holds for a monolayer of water in
      nanoconfinement.

PMID- 22998275
TI  - Thermal tweezers for nano-manipulation and trapping of interacting atoms or
      nanoparticles on crystalline surfaces.
AB  - Thermal tweezers is an all-optical nanofabrication technique where surface
      thermophoresis due to holographically induced strong temperature modulation is
      used for parallel manipulation and trapping of adatoms and adparticles with
      nanoscale resolution. This paper conducts the detailed numerical analysis of
      thermal tweezers in the presence of significant interaction between the
      adparticles on the surface. In particular, we demonstrate that the considered
      inter-particle interactions result in a significant enhancement of the surface
      thermophoretic effect and substantially increases modulation of particle
      concentration on the surface. In addition, we predict the possibility to achieve
      adparticle confinement on the surface to strongly sub-wavelength regions ~12
      times smaller than the vacuum wavelength of the optical radiation. A numerical
      approach to surface diffusion of interacting nanoparticles and adatoms is
      developed, the Monte Carlo interaction method, and its applicability conditions
      and limitations are discussed. The obtained results will be important for better
      understanding of the fundamental aspects of surface thermophoresis, as well as
      the development of new approaches to nano-patterning of surfaces for engineering
      their optical, electronic, chemical, and mechanical properties by means of the
      directed self-assembly of nanoparticles and adatoms.

PMID- 22998276
TI  - Energy transfer in finite-size exciton-phonon systems: confinement-enhanced
      quantum decoherence.
AB  - Based on the operatorial formulation of the perturbation theory, the exciton
      phonon problem is revisited for investigating exciton-mediated energy flow in a
      finite-size lattice. Within this method, the exciton-phonon entanglement is taken
      into account through a dual dressing mechanism so that exciton and phonons are
      treated on an equal footing. In a marked contrast with what happens in an
      infinite lattice, it is shown that the dynamics of the exciton density is
      governed by several time scales. The density evolves coherently in the short-time
      limit, whereas a relaxation mechanism occurs over intermediated time scales.
      Consequently, in the long-time limit, the density converges toward a nearly
      uniform distributed equilibrium distribution. Such a behavior results from
      quantum decoherence that originates in the fact that the phonons evolve
      differently depending on the path followed by the exciton to tunnel along the
      lattice. Although the relaxation rate increases with the temperature and with the
      coupling, it decreases with the lattice size, suggesting that the decoherence is
      inherent to the confinement.

PMID- 22998277
TI  - Microphase separations of the fluids with spherically symmetric competing
      interactions.
AB  - A density functional perturbation theory has been developed for studying the
      phase behaviors of a competing system in the spherical pores. The pore size as
      well as the intensity of competing interactions exerts a strong influence on the
      vapor-liquid, vapor-cluster, and cluster-liquid transitions of a competing
      system. The microdomain spacing (D) of the cluster is commensurate with the
      periodicity of modulation in the particle density distributions of a competing
      system in a spherical pore with the pore radius (R). For the cluster phase, we
      find that the multi-vaporlike void is formed depending on the periodicity of
      modulation by finite-size artifacts. For R < D, the competing system only shows
      the vapor-liquid transition at a high amplitude. For R > D, the vapor-cluster and
      cluster-liquid transitions are found at a high amplitude, whereas at a low
      amplitude, the cluster-liquid transition only occurs. The competing system
      exhibits two tricritical points, which are joined to one another by the line of
      second-order transitions at the low and high densities. A comparison with the
      result of a slit pore shows that (i) the tricritical points in a spherical pore,
      which has the highest symmetry, occur at a low amplitude compared with that of a
      slit pore because of the geometrical properties of the pores, and that (ii) the
      slit pore relatively shows the wide vapor-cluster and cluster-liquid coexistence
      regions compared with that of a spherical pore: the geometrical symmetry of a
      pore results in a weaker tendency for phase separation.

PMID- 22998278
TI  - Electromagnetic fluctuation-induced interactions in randomly charged slabs.
AB  - Randomly charged net-neutral dielectric slabs are shown to interact across a
      featureless dielectric continuum with long-range electrostatic forces that scale
      with the statistical variance of their quenched random charge distribution and
      inversely with the distance between their bounding surfaces. By accounting for
      the whole spectrum of electromagnetic field fluctuations, we show that this long
      range disorder-generated interaction extends well into the retarded regime where
      higher order (non-zero) Matsubara frequencies contribute significantly. This
      occurs even for highly clean samples with only a trace amount of charge disorder
      and shows that disorder effects can be important down to the nanoscale. As a
      result, the previously predicted non-monotonic behavior for the total force
      between dissimilar slabs as a function of their separation distance is
      substantially modified by higher order contributions, and in almost all cases of
      interest, we find that the equilibrium inter-surface separation is shifted to
      substantially larger values compared to predictions based solely on the zero
      frequency component. This suggests that the ensuing non-monotonic interaction is
      more easily amenable to experimental detection. The presence of charge disorder
      in the intervening dielectric medium between the two slabs is shown to lead to an
      additional force that can be repulsive or attractive depending on the system
      parameters and can, for instance, wash out the non-monotonic behavior of the
      total force when the intervening slab contains a sufficiently large amount of
      disorder charges.

PMID- 22998279
TI  - Embedded cluster density functional and second-order Moller-Plesset perturbation
      theory study on the adsorption of N2 on the rutile (110) surface.
AB  - The adsorption of N(2) on the rutile TiO(2) (110) surface in the limit of low
      coverage has been studied as a prototype example for the adsorption of non-polar
      molecules on strongly ionic oxide surfaces. We employed for this study an
      embedded cluster ansatz in combination with density functional theory and
      wavefunction methods. Both, clusters saturated with hydrogen atoms and
      electrostatically embedded clusters have been applied and methods and basis sets
      have been varied to test their reliability and accuracy for describing the
      electrostatic potential on the surface and its interaction with the non-polar
      N(2) molecule. Quantum clusters consisting of up to 342 atoms have been used to
      converge the results with respect to the cluster size. For electrostatically
      embedded clusters, the convergence can considerably be enhanced by optimizing the
      charges for the point charge embedding. On the rutile (110) surface an accurate
      account of the long ranging interaction of the adsorbate with the bridging oxygen
      atoms is important for quantitative adsorption energies of weakly bound
      molecules. In addition the geometric relaxation of the surface has a marked
      influence on the results, whereas the basis set-dependence is small. Of all
      methods investigated (HF, DFT/PBE, DFT/B3LYP, MP2), only MP2 and DFT/B3LYP were
      able to describe the adsorption of N(2) on the rutile surface properly. After
      including the zeropoint vibrational energy, the calculated adsorption energy is
      close to experimental results. The approach is thus promising for future
      investigations on adsorption energies and structures of non-polar molecules on
      ionic oxide surfaces.

PMID- 22998280
TI  - The structure of ionic aqueous solutions at interfaces: an intrinsic structure
      analysis.
AB  - We investigate the interfacial structure of ionic solutions consisting of alkali
      halide ions in water at concentrations in the range 0.2-1.0 molal and at 300 K.
      Combining molecular dynamics simulations of point charge ion models and a
      recently introduced computational approach that removes the averaging effect of
      interfacial capillary waves, we compute the intrinsic structure of the aqueous
      interface. The interfacial structure is more complex than previously inferred
      from the analysis of mean profiles. We find a strong alternating double layer
      structure near the interface, which depends on the cation and anion size.
      Relatively small changes in the ion diameter disrupt the double layer structure,
      promoting the adsorption of anions or inducing the density enhancement of small
      cations with diameters used in simulation studies of lithium solutions. The
      density enhancement of the small cations is mediated by their strong water
      solvation shell, with one or more water molecules "anchoring" the ion to the
      outermost water layer. We find that the intrinsic interfacial electrostatic
      potential features very strong oscillations with a minimum at the liquid surface
      that is ~4 times stronger than the electrostatic potential in the bulk. For the
      water model employed in this work, SPC/E, the electrostatic potential at the
      water surface is ~-2 V, equivalent to ~80 k(B)T (for T = 300 K), much stronger
      than previously considered. Furthermore, we show that the utilization of the
      intrinsic surface technique provides a route to extract ionic potentials of mean
      force that are not affected by the thermal fluctuations, which limits the
      accuracy of most past approaches including the popular umbrella sampling
      technique.

PMID- 22998281
TI  - Origin of enhanced water adsorption at <110> step edge on rutile TiO2(110)
      surface.
AB  - Water adsorption behavior at <110> and <001> step edges on rutile TiO(2) (110)
      surface has been investigated using density-functional theory calculations. We
      find that the <110> edge exhibits significantly enhanced water adsorption,
      especially dissociative adsorption, as compared to the pristine (110) surface and
      <001> step edge. The origin for the enhanced water adsorption is found to be due
      to the existence of fourfold coordinated Ti atoms (Ti(4c)) at the <110> step
      edge, which lead to charge transfer to adsorbates more easily than fivefold
      coordinated Ti atoms on the (110) surface and <001> step edge. Furthermore, due
      to the local configuration of the dissociative mode, the charge transfer occurs
      more easily from Ti(4c) to the hydroxyl group 1pi orbital, which considerably
      increases the adsorbate-substrate interaction. As a result, the <110> step edge
      favors dissociative water adsorption, making it more reactive to water than the
      (110) surface and <001> edge.

PMID- 22998282
TI  - Surface tension and phase coexistence for fluids of molecules with extended
      dipoles.
AB  - Molecular dynamics simulations of fluids of molecules with extended dipoles were
      performed, with increasing distance between point charges but with a constant
      dipole moment, to obtain thermodynamic properties. It was found that the effect
      of varying the dipole length on the dielectric constant in the liquid phase, the
      vapor-liquid equilibria, and the surface tension was negligible for dipolar
      lengths up to half the particle diameter. By comparing thermodynamic properties
      of the predictions of the extended dipole model with those for the Stockmayer
      fluid of point dipoles, it was found that extended dipoles are equivalent to
      point dipoles over a wide range of dipole lengths, and not only near the point
      dipole limit, when the separation length is very small compared with the mean
      distance between particles. Finally, phase equilibrium results of extended
      dipoles were compared to those obtained from the discrete perturbation theory for
      a Stockmayer potential.

PMID- 22998283
TI  - Effect of dispersion correction on the Au(1 1 1)-H2O interface: a first
      principles study.
AB  - A theoretical study of the H(2)O-Au(1 1 1) interface based on first principles
      density functional theory (DFT) calculations with and without inclusion of
      dispersion correction is reported. Three different computational approaches are
      considered. First, the standard generalized gradient approximation (GGA)
      functional PBE is employed. Second, an additional energy term is further included
      that adds a semi-empirically derived dispersion correction (PBE-D2), and,
      finally, a recently proposed functional that includes van der Waals (vdW)
      interactions directly in its functional form (optB86b-vdW) was used to represent
      the state-of-the art of DFT functionals. The monomeric water adsorption was first
      considered in order to explore the dependency of geometry on the details of the
      model slab used to represent it (size, thickness, coverage). When the dispersion
      corrections are included the Au-H(2)O interaction is stronger, as manifested by
      the smaller d(Au-O) and stronger adsorption energies. Additionally, the
      interfacial region between Au(1 1 1) slab surfaces and a liquid water layer was
      investigated with Born-Oppenheimer molecular dynamics (BOMD) using the same
      functionals. Two or three interfacial orientations can be determined, depending
      on the theoretical methodology applied. Closest to the surface, H(2)O is adsorbed
      O-down, whereas further away it is oriented with one OH bond pointing to the
      surface and the molecular plane parallel to the normal direction. For the optB86b
      vdW functional a third orientation is found where one H atom points into the bulk
      water layer and the second OH bond is oriented parallel to the metal surface. As
      for the water density in the first adsorption layer we find a very small increase
      of roughly 8%. From the analysis of vibrational spectra a weakening of the H-bond
      network is observed upon the inclusion of the Au(1 1 1) slab, however, no
      disruption of H-bonds is observed. While the PBE and PBE-D2 spectra are very
      similar, the optB86b-vdW spectrum shows that the H-bonds are even more weakened.

PMID- 22998284
TI  - Monte Carlo simulations of charge transport in organic systems with true off
      diagonal disorder.
AB  - In this work, a novel method to model off-diagonal disorder in organic materials
      has been developed. The off-diagonal disorder is taken directly from the geometry
      of the system, which includes both a distance and an orientational dependence on
      the constituent molecules, and does not rely on a parametric random distribution.
      The geometry of the system is generated by running molecular dynamics simulations
      on phenylene-vinylene oligomers packed into boxes. The effect of the kind of
      randomness generated in this way is then investigated by means of Monte Carlo
      simulations of the charge transport in these boxes and a comparison is made to
      the commonly used model of off-diagonal disorder, where only the distance
      dependence is accounted for. It is shown that this new refined way of treating
      the disorder has a significant impact on the charge transport, while still being
      compliant with previously published and confirmed results.

PMID- 22998285
TI  - Unexpected crossover dynamics of single polymer in a corrugated tube.
AB  - We present molecular dynamics study of a generic (coarse-grained) model for
      single-polymer diffusion confined in a corrugated cylinder. For a narrow tube,
      i.e., diameter of the cylinder delta < 2.3, the axial diffusion coefficient D(??)
      scales as D(??) ? N(-3/2), with chain length N, up to N ~ 100 and then crosses
      over to Rouse scaling for the larger N values. The N(-3/2) scaling is due to the
      large fluctuation of the polymer chain along its fully stretched equilibrium
      conformation. The stronger scaling, namely N(-3/2), is not observed for an
      atomistically smooth tube and/or for a cylinder with larger diameter.

PMID- 22998286
TI  - Crossover time in relative fluctuations characterizes the longest relaxation time
      of entangled polymers.
AB  - In entangled polymer systems, there are several characteristic time scales, such
      as the entanglement time and the disengagement time. In molecular simulations,
      the longest relaxation time (the disengagement time) can be determined by the
      mean square displacement (MSD) of a segment or by the shear relaxation modulus.
      Here, we propose the relative fluctuation analysis method, which is originally
      developed for characterizing large fluctuations, to determine the longest
      relaxation time from the center of mass trajectories of polymer chains (the time
      averaged MSDs). Applying the method to simulation data of entangled polymers (by
      the slip-spring model and the simple reptation model), we provide a clear
      evidence that the longest relaxation time is estimated as the crossover time in
      the relative fluctuations.

PMID- 22998287
TI  - Mixing normal and anomalous diffusion.
AB  - In the densely filled biological cells often subdiffusion is observed, where the
      average squared displacement increases slower than linear with the length of the
      observation interval. One reason for such subdiffusive behavior is attractive
      interactions between the diffusing particles that lead to temporary complex
      formation. Here, we show that such transient binding is not an average state of
      the particles but that intervals of free diffusion alternate with slower
      displacement when bound to neighboring particles. The observed macroscopic
      behavior is then the weighted average of these two contributions. Interestingly,
      even at very high concentrations, the unbound fraction still exhibits essentially
      normal diffusion.

PMID- 22998288
TI  - HP-sequence design for lattice proteins--an exact enumeration study on diamond as
      well as square lattice.
AB  - We present an exact enumeration algorithm for identifying the native
      configuration--a maximally compact self-avoiding walk configuration that is also
      the minimum energy configuration for a given set of contact-energy schemes; the
      process is implicitly sequence-dependent. In particular, we show that the 25-step
      native configuration on a diamond lattice consists of two sheet-like structures
      and is the same for all the contact-energy schemes, {(-1, 0, 0); (-7, -3, 0); (
      7, -3, -1); (-7, -3, 1)}; on a square lattice also, the 24-step native
      configuration is independent of the energy schemes considered. However, the
      designing sequence for the diamond lattice walk depends on the energy schemes
      used whereas that for the square lattice walk does not. We have calculated the
      temperature-dependent specific heat for these designed sequences and the four
      energy schemes using the exact density of states. These data show that the energy
      scheme (-7, -3, -1) is preferable to the other three for both diamond and square
      lattice because the associated sequences give rise to a sharp low-temperature
      peak. We have also presented data for shorter (23-, 21-, and 17-step) walks on a
      diamond lattice to show that this algorithm helps identify a unique minimum
      energy configuration by suitably taking care of the ground-state degeneracy.
      Interestingly, all these shorter target configurations also show sheet-like
      secondary structures.

PMID- 22998290
TI  - Note: Photoelectron spectroscopy of cold UF5(-).

PMID- 22998289
TI  - Absolute cross sections for vibrational excitations of cytosine by low energy
      electron impact.
AB  - The absolute cross sections (CSs) for vibrational excitations of cytosine by
      electron impact between 0.5 and 18 eV were measured by electron-energy loss (EEL)
      spectroscopy of the molecule deposited at monolayer coverage on an inert Ar
      substrate. The vibrational energies compare to those that have been reported from
      IR spectroscopy of cytosine isolated in Ar matrix, IR and Raman spectra of
      polycrystalline cytosine, and ab initio calculation. The CSs for the various H
      bending modes at 142 and 160 meV are both rising from their energy threshold up
      to 1.7 and 2.1 * 10(-17) cm(2) at about 4 eV, respectively, and then decrease
      moderately while maintaining some intensity at 18 eV. The latter trend is
      displayed as well for the CS assigned to the NH(2) scissor along with bending of
      all H at 179 meV. This overall behavior in electron-molecule collision is
      attributed to direct processes such as the dipole, quadrupole, and polarization
      contributions, etc. of the interaction of the incident electron with a molecule.
      The CSs for the ring deformation at 61 meV, the ring deformation with N-H
      symmetric wag at 77 meV, and the ring deformations with symmetric bending of all
      H at 119 meV exhibit common enhancement maxima at 1.5, 3.5, and 5.5 eV followed
      by a broad hump at about 12 eV, which are superimposed on the contribution due to
      the direct processes. At 3.5 eV, the CS values for the 61-, 77-, and 119-meV
      modes reach 4.0, 3.0, and 4.5 * 10(-17) cm(2), respectively. The CS for the C-C
      and C-O stretches at 202 meV, which dominates in the intermediate EEL region,
      rises sharply until 1.5 eV, reaches its maximum of 5.7 * 10(-17) cm(2) at 3.5 eV
      and then decreases toward 18 eV. The present vibrational enhancements, correspond
      to the features found around 1.5 and 4.5 eV in electron transmission spectroscopy
      (ETS) and those lying within 1.5-2.1 eV, 5.2-6.8 eV, and 9.5-10.9 eV range in
      dissociative electron attachment (DEA) experiments with cytosine in gas phase.
      While the ETS features are ascribed to shape resonances associated with the
      electron occupation of the second and third antibonding pi-orbitals of the
      molecule in its ground state, the correspondence with DEA features suggests the
      existence of common precursor anion states decaying with certain probabilities
      into the vibrationally excited ground state.

PMID- 22998291
TI  - Note: On the power spectrum of undulations of simulated bilayers.
AB  - The best finite Fourier series for a smooth surface h(x, y), closest to the
      positions of heads of amphiphiles in the least-square sense, agrees fully with
      the Fourier coefficients obtained by a direct summation over raw data points.
      Both methods produce structure factors S(q) containing all necessary features:
      small-q divergence, a minimum, the raise to the ubiquitous nearest-neighbor peak
      near q = 2pi/(coll.diameter) and further peaks. The Laurent series is also
      discussed.

PMID- 22998292
TI  - Metabolic and toxicological considerations for sepsis drug treatments.
AB  - INTRODUCTION: Sepsis, a complex interaction between pathogen and host response,
      presents a difficult challenge for clinicians and researchers alike. With an
      increasing understanding of the pathophysiology of the disease, new treatment
      paradigms are evolving. AREAS COVERED: This article reviews the metabolic and
      toxicological considerations in sepsis, including the unique issues involved in
      neonatal and pediatric populations that differentiate it from adult sepsis. The
      authors cover metabolic issues, such as perfusion, renal and hepatic dysfunction
      and fluid retention in conjunction with their impact on therapy. Furthermore, the
      authors examine toxicological considerations of nephrotoxicity, ototoxicity and
      adverse drug reactions. The authors also present novel biomarkers of sepsis and
      current clinical tests utilized for the diagnosis of sepsis, as well as the
      limitations in animal models of sepsis and newer therapies. An extensive
      literature search including relevant formulae, publications and textbooks serves
      as the basis for this review. EXPERT OPINION: Improving understanding of the
      metabolic and toxicological issues in sepsis will allow the development of more
      effective multifaceted treatments and reduction of risks. Clinical research will
      need to more heavily involve neonatal and pediatric patients given the number of
      individuals who die from sepsis within these special populations. Development of
      a sepsis-specific inflammatory biomarker would allow more rapid detection as well
      as a method to determine the effectiveness of novel therapies.

PMID- 22998293
TI  - The impact of UVB exposure and differentiation state of primary keratinocytes on
      their interaction with quantum dots.
AB  - In this study we utilised an in vitro model system to gain insight into the
      potential cellular interactions that quantum dot (QD) nanoparticles may
      experience while transiting the viable skin epidermis, and we consider the
      effects of UVB exposure. UVB skin exposure is known to induce a skin barrier
      defect that facilitates QD stratum corneum penetration. Primary human
      keratinocytes were cultured in low and high calcium to induce basal and
      differentiated phenotypes, respectively. Results suggest that differentiation
      state plays a role in keratinocyte response to UVB exposure and exposure to
      negatively charged CdSe/ZnS core/shell QD. QD cell uptake increased with QD dose
      but association with differentiated cells was significantly lower than the basal
      keratinocyte phenotype. Differentiated keratinocytes were also less sensitive to
      the cytotoxic effects of UVB exposure. We did not observe an effect of UVB
      preexposure on QD cytotoxicity level despite the fact that fluorescent microscopy
      and flow cytometry data suggest that UVB may slightly increase QD uptake in the
      basal cell phenotype. The implications of these findings for assessing potential
      risk of human skin exposure are discussed.

PMID- 22998294
TI  - Window of opportunity for neuroprotection with an antioxidant, allene oxide
      synthase, after hypoxia-ischemia in adult male rats.
AB  - AIMS: Oxidative stress is an early event in the cascade leading in neuronal
      damage after hypoxic-ischemic (HI) brain injury. In the present study, we
      examined the dose response and window of opportunity for neuroprotection after HI
      injury with Allene Oxide Synthase (AOS), an anti-oxidative enzyme of the member
      of cytochrome P450 family. METHODS: Adult male rats received intra-cerebro
      ventricular infusions of either saline (vehicle) or AOS (1 MUg or 10 MUg or 100
      MUg per rat, intracerebroventricular n = 16 all groups) either 45 min or 3 h
      after unilateral HI brain injury. Brains were collected 5 days later. The extent
      of brain damage, neuronal survival, apoptosis, and glial reactions were assessed
      in the striatum, hippocampus, and cortex. RESULTS: Allene Oxide Synthase was
      associated with reduced neuronal damage scores when given 45 min, but not 3 h,
      after HI injury (P < 0.0001) in all brain regions. AOS treatment (10 MUg)
      improved neuronal survival in the striatum, cortex, and hippocampus (P < 0.05, P
      < 0.001) and reduced the microglia reaction (P < 0.05) and numbers of caspase-3
      positive cells in the hippocampus (P < 0.01). CONCLUSIONS: Early blockade of
      oxidative stress after HI injury reduces inflammatory response, neuronal
      necrosis, and apoptosis. The neuroprotective effects of AOS were time of
      administration-dependent suggesting a relatively restricted window of opportunity
      for acute brain injury.

PMID- 22998295
TI  - Combination of beta-cyclodextrin inclusion complex and self-microemulsifying drug
      delivery system for photostability and enhanced oral bioavailability of
      methotrexate: novel technique.
AB  - In the present study, we prepared an inclusion complex of methotrexate (MTX) with
      beta-cyclodextrin (beta-CD) in order to decrease its photosensitivity and enhance
      its aqueous solubility. Then we incorporated this inclusion complex in a self
      microemulsifying drug delivery system (SMEDDS) overall to increase its oral
      bioavailability. The inclusion complex has been prepared by freeze drying method
      and characterized by differential scanning calorimetry (DSC), ultraviolet (UV),
      and infrared (IR) spectroscopy assays. The proper molecular ratio of MTX/beta-CD
      was found to be of 1:7, and the water-solubility of MTX was increased in an
      average of 10-fold. The photostability studies showed that the MTX became stable
      on exposure to light. Construction of pseudoternary diagrams were investigated to
      prepare a MTX/beta-CD inclusion complex loaded SMEDDS which was characterized by
      measuring the particle size and the zeta-potential. The optimum formulation of
      SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol
      with a mean droplet size of 39.42 nm. In vitro drug release in different pH media
      showed that the release profile of MTX from the MTX/beta-CD loaded SMEDDS was
      influenced by the pH of the release medium and presented the characteristics of a
      sustained release profile. Finally, in-vivo studies showed an enhancement of the
      bioavailability of MTX from the MTX/beta-CD loaded SMEDDS form of 1.57-fold. We
      concluded that the beta-CD inclusion complex loaded SMEDDS improved the chemical
      and physiological properties of MTX and could be a promising means for the
      delivery of MTX and other unstable and lipophilic drugs by oral route.

PMID- 22998296
TI  - Guest editorial on the Festschrift "Challenges in population oral health for the
      21st century".
AB  - This Festschrift provides important and valuable guidance on population oral
      health. It is unfortunate that it coincides with the retirement of one of
      population oral health's pioneers, Professor John (AJ) Spencer, who has made
      significant contributions to the subject over the last 35 years. Oral diseases
      and disorders remain prevalent and have detrimental effects on individuals, and
      society-at-large. Many of our attempts to improve population oral health through
      existing oral health services have met with limited success, owing to the focus
      on 'care' rather than 'cure'. It has long been recognised that oral diseases are
      largely behavioural in origin; but this approach at the individual level has not
      been entirely successful. There is a need to consider 'mid- and up-stream'
      approaches to changing oral health and health care delivery systems. However
      social inequalities are a major determinant of oral health, and their influence
      in oral health are omnipresent, which emphasises the important role of population
      oral health in future health care strategies. The Festschrift provides
      theoretical and empirical evidence of the need for further epidemiological
      investigations (particularly life course studies), innovative approaches to oral
      health surveillance and oral health outcome evaluation, plus a realisation that
      multidisciplinary approaches are the way forward. In an information and
      globalization era, we must put the 'population' into oral health and this is our
      challenge for the 21st Century.

PMID- 22998297
TI  - Putting the population back into oral health; decoupling oral health improvement
      from clinical dental practice.
AB  - Some 20 years ago, there was much speculation about improving oral health and the
      subsequent emergence of a vastly different type of clinical dental practice and
      vis versa. Few of the predictions have come to pass in Australia. Caries in
      children has somewhat rebounded, new treatment philosophies have not gained
      widespread adoption, and work effort in clinical dental practice remains
      dominated by diagnostic services, restorations and removable prosthodontics. What
      was behind the wayward predictions was a failure to separate the potency of
      'care' from ability to 'cure' and an overestimation of the improvement in child
      oral health attributable to clinical dental services. If progress is to be made
      in improving oral health, an understanding of the mid- and upstream determinants
      of oral health needs to guide new population oral health activities. The
      contribution of clinical dental services to oral health should also be enhanced,
      but this should not divert attention from necessary population oral health
      activities to improve oral health.

PMID- 22998298
TI  - What do we mean by population health?
AB  - The term 'population health' is part of the natural evolution of the science of
      epidemiology. With the recognition of the importance of a life-course approach to
      help understand health along with the recognition of the importance of the wider
      determinants of health, epidemiology requires new techniques and thinking.
      'Population health' recognizes that to improve oral health, then the determinants
      have to be tackled. These include both those that may be described as belonging
      to the environment and those influenced by the care system. The key issue for
      policy development is the need to recognize that with globalization and the
      extended time frame to undertake research, partnerships will be a key necessity
      to help ensure success in addressing inequalities and overall levels of health.

PMID- 22998299
TI  - The influence of population oral health on the dental team.
AB  - This presentation focuses on the use of dental therapists as substitutes for
      dentists in the provision of some aspects of dental care. Our premise is that the
      use of therapists is a 'good thing' if it delivers a higher quality service. The
      care that may be provided by therapists is appropriate to population needs. They
      have been used to increase access to care in a number of countries by
      supplementing the volume and reach of services, which enhances equity. Therapists
      are socially acceptable where they are integrated into existing dental systems,
      but concerted work may be necessary to increase their acceptability if their use
      is to be introduced or expanded elsewhere. There is no reason to suspect that
      therapists offer less effective care than dentists, and available data are
      compatible with this view. More data may be required to lend political support
      for their greater use. The efficiency of teams is sensitive to the way in which
      they are organized and funded. Substitution of dentists by therapists within
      small dental teams creates complexities and costs that reduce efficiency.
      Conversely, where therapists can work with relative independence, diagnosing and
      treating patients without direct supervision, then efficiency may be high.
      Despite opportunities for improving the quality of care, the main barrier for
      increasing their use is the dental profession. Dental organizations tend to act
      as guilds, preventing or restricting the deployment of therapists. Dental public
      health practitioners therefore have a role as advocates for their greater use. At
      present, the use of therapists does not appear to be influenced by the health of
      the population.

PMID- 22998300
TI  - Targeting in a population health approach.
AB  - There are two well described methods to improving health: an individual risk
      assessment approach and a whole population approach. OBJECTIVES: This study
      explores the limitations of the individual approach to public health, and the
      success and limitations of the population approach. METHODS: A theoretical
      approach with examples from general and oral health will be used. RESULTS:
      However although the population approach can reduce the mean prevalence of a
      condition within the population it can also increase health disparities. Some
      groups gain disproportionally more from a population intervention and vulnerable
      population groups disproportionally less leading to an unjust situation. These
      disparities are the result of social circumstances. CONCLUSIONS: Additional
      strategies targeted to vulnerable groups are therefore necessary to complement
      the population approach to reduce such disparities. Examples of strategies which
      could be used in targeting vulnerable groups will be outlined.

PMID- 22998301
TI  - Social inequality in oral health.
AB  - Social inequalities in oral health are observable regardless of the population,
      the culture, the method of social classification or the measure of oral health or
      disease. They exist because of socially determined differences in opportunity,
      behaviours, beliefs and exposure to the myriad factors which determine our oral
      health. Behaviours and practices which affect oral health are embedded in the
      normal patterns of everyday life; those (in turn) are socially determined and
      differ across the continuum of social status. This presentation focuses primarily
      on social inequalities in incremental tooth loss because (i) it is a condition
      which has been shown to have the greatest effect on people's oral-health-related
      quality of life, and (ii) it is cumulative and irreversible. Most of the
      knowledge base on social inequalities in tooth loss comes from cross-sectional
      studies; investigating the phenomenon in a birth cohort can be more informative
      because it allows us to determine what happens to those inequalities through the
      life course. Data on incremental tooth loss from a longstanding cohort study (the
      Dunedin Multidisciplinary Health and Development Study) are presented to
      illustrate the cumulative and pervasive effect of social inequalities and changes
      in social status between childhood and adulthood.

PMID- 22998302
TI  - How will a life course framework be used to tackle wider social determinants of
      health?
AB  - The life course framework, proposed by Kuh and Schlomo in 1997, offers policy
      makers the means to understand the interaction between nature and nurture. This
      conceptual model illustrates how an individual's biological resources are
      influenced by their genetic endowment, their prenatal and postnatal development
      and their social and physical environment, both in early life and throughout the
      life course. Health is conceptualized as a dynamic process connecting biological
      and social elements that are affected by previous experiences and by present
      circumstances. Therefore, exposure at different stages of people's lives can
      either enhance or deplete the individual's health resources. Indeed, life course
      processes are of many kinds, including parent-child relationships, levels of
      social deprivation, the acquisition of emotional and behavioural assets in
      adolescence and the long-term effects of occupational hazards and work stress.
      The long-term effects of nature and nurture combine to influence disease
      outcomes. It is only in the last decade that theories, methods and new data have
      begun to be amalgamated, allowing us to further our understanding of health over
      the life course in ways that may eventually lead to more effective health
      policies and better health care. This article discusses life course concepts and
      how this framework can enlighten our understanding of wider social determinants
      of health, and provides a few examples of potential interventions to tackle their
      impact on health.

PMID- 22998303
TI  - Oral health-related quality of life is important for patients, but what about
      populations?
AB  - OBJECTIVES: To review population-based research into oral health-related quality
      of life. METHODS: Narrative review of selected publications. RESULTS: In the
      1970s, there were two incentives to assess nonclinical aspects of health: (i) a
      desire to understand the impacts of disease on individuals' quality of life; and
      (ii) a search for population-level measures that might better quantify the impact
      of health care systems on populations. Dental researchers responded to those
      incentives, creating dozens of questionnaires that assess individuals' ratings of
      subjective oral health and quality of life. This has been a boon for clinical
      dental research, for example, by showing marked improvements in subjective oral
      health in patients receiving implant-supported dentures. Also, health surveys
      show poorer subjective oral health among disadvantaged population groups.
      However, the same measures show only modest benefits of general dental care.
      Furthermore, several population surveys show that today's young adults, who grew
      up with widespread exposure to preventive dental programs, have poorer subjective
      oral health than earlier generations that experienced unprecedented levels of
      oral disease. Yet to materialize is the hope that 'socio-dental indicators' of
      subjective oral health might provide a meaningful metric to demonstrate
      population-level benefits of dental care. A fundamental limitation is that
      population health is a contextual measure, not merely the aggregated health
      status of individuals within the population. CONCLUSION: While researchers have
      successfully broken with clinical dogma by assessing subjective dimensions of
      individuals' oral health, they have failed to explicitly ask people to assess the
      oral health of the community in which they live.

PMID- 22998304
TI  - Social determinants of oral health inequalities: implications for action.
AB  - For over 30 years, the WHO has been advocating an integrated approach in chronic
      disease prevention. The concept of the common risk factor approach (CRFA)
      highlighted shared risk factors for chronic conditions including oral diseases
      has provided the basis for closer integration of oral and general health
      promotion activities. Although considerable progress has been undoubtedly made in
      combating the isolation and compartmentalization of oral health, this paper will
      argue that future action on tackling oral health inequalities requires a
      reorientation of oral health policy away from a fixation on changing oral health
      behaviours to instead action on the common social determinants of oral health
      inequalities. The narrow and restricted interpretation of the CRFA is a serious
      threat to developing effective action to address oral health inequalities. Based
      upon the WHO conceptual framework on the social determinants of health
      inequalities, an overview will be presented of a range of actions that could be
      implemented to tackle the social gradients in oral health outcomes.

PMID- 22998305
TI  - Interdisciplinary health promotion: a call for theory-based interventions drawing
      on the skills of multiple disciplines.
AB  - Promoting the health of populations demands the adoption of a perspective
      exploring the societal, political, community, family and individual determinants
      of health. I will argue that to develop interventions to modify health-related
      behaviours and health risks requires collaboration with a range of disciplines,
      in order to draw upon their theoretical, empirical and oftentimes political
      knowledge. To illustrate this thesis, I will draw upon research in three areas:
      improving oral health-related behaviours in individuals with periodontal disease
      and childhood caries; encouraging early recognition in head and neck cancer; and
      managing dental anxiety. Reviews of oral health education in the early 1990 s
      suggested that approaches based on education were largely ineffective in the
      absence of the provision of fluoride supplementation. More recently, high-quality
      research has identified simple, theory-based interventions that can improve
      adherence to specific oral hygiene-related behaviours. Similarly, a range of
      studies have demonstrated the effectiveness of motivational interviewing for
      targeting caries-related behaviours in targeted groups. Dental anxiety remains a
      significant barrier to the uptake of dental services, and again, by working in
      multi-disciplinary teams, a proportionate and comprehensive range of
      interventions can be adopted to alleviate the burden of dental fear. Finally,
      head and neck cancer has potentially serious effects for sufferers, but often
      presents late for a variety of reasons. Through developing a theoretical model of
      help-seeking behaviour, psychologists have been able to identify targets for
      interventions and work together with the healthcare team to develop these.

PMID- 22998306
TI  - Effectiveness of water fluoridation in caries prevention.
AB  - OBJECTIVES: To review the effectiveness of adjusted fluoridation of public water
      supplies in the prevention of dental caries, with emphasis on results of studies
      published worldwide since 1990 and to discuss aspects of the design and reporting
      of these studies compared with those published before 1990. METHOD: Studies
      published worldwide, in any language, reporting the effect of water fluoridation
      in terms of the dmf/DMF caries index between 1990 and 2010 were examined. The
      literature search was by professional Internet search, back-tracking from
      references given in publications, hand-searching all issues of four journals and
      by contacting colleagues in relevant countries. For the dmf index, age 5 year was
      preferred, and for the DMF index, age 12 year or older was preferred. The results
      were compared with results obtained from worldwide literature search prior to
      1990 by the same author. RESULTS: Fifty-nine studies of adjusted water
      fluoridation were identified, yielding 83 evaluations (30 recording dmft/s and 53
      recording DMFT/S) from 10 countries. These numbers are lower than pre-1990
      results of 113 studies (66 for primary and 86 for permanent teeth) from 23
      countries. For the USA, for example, four studies were identified since 1990
      compared with 61 studies before 1990. The most number of recent reports came from
      Brazil and Australia. There were fewer reports of per cent caries reductions (%
      CR) above 50% in the recent studies. 86% of the post-1990 investigations were
      concurrent control cross-sectional studies and, of these, 52% used multivariate
      statistical analysis to adjust for confounding factors. In the eight studies that
      provided dmf/DMF data before and after adjustment for confounders, the % CR were
      little affected by these adjustments. CONCLUSIONS: Fewer studies have been
      published recently. More of these have investigated effect at the multi
      community, state or even national level. The dmf/DMF index remains the most
      widely used measure of effect. % CR were lower in recent studies, and the 'halo'
      effect was discussed frequently. Nevertheless, reductions were still substantial.
      Statistical control for confounding factors is now routine, although the effect
      on per cent reductions tended to be small. Further thought is needed about the
      purpose of evaluation and whether measures of effect and study design are
      appropriate for that purpose.

PMID- 22998307
TI  - The revival of water fluoridation in the state of New South Wales, Australia, in
      the 21st century.
AB  - The State of New South Wales (NSW) in Australia has over half a century of
      experience with water fluoridation. Yass was the first town to be fluoridated in
      1956 and Sydney in 1968, and by the late 1970s, approximately 90% of NSW was
      fluoridated. However, since then, there have been no new fluoridation schemes. In
      NSW under the Fluoridation of Public Water Supplies Act 1957, the decision to
      fluoridate rests with local government authorities (councils). Since 2004, the
      NSW Health Department has been proactive in promoting and extending water
      fluoridation to unfluoridated rural communities in an attempt to reduce oral
      health inequalities. This has resulted in 20 councils implementing fluoridation,
      increasing population coverage of water fluoridation from 90% in 2004 to 96% in
      2012. When the remaining 16 councils that have been gazetted to fluoridate
      implement fluoridation, approximately 98% of NSW residents will have access to
      fluoridated water. This article provides an overview of the framework used to
      extend water fluoridation to many rural communities in New South Wales in the
      21st century.

PMID- 22998308
TI  - Water fluoridation in Victoria, Australia: the value of national research.
AB  - Water fluoridation has become the centrepiece in dental caries prevention for the
      Australian population since its introduction in 1953 in Beaconsfield, Tasmania.
      With the notable exception until recently of Brisbane, residents of the state and
      territory capital cities have enjoyed the dental health benefits of this
      important public health initiative for at least 33 years. For many communities in
      rural and regional Australia, however, the introduction of water fluoridation has
      only commenced in relative recent years - if at all. These efforts in recent
      years have been greatly assisted by the research of Professor John Spencer and
      his colleagues at the Australian Research Centre for Population Oral Health
      (ARCPOH). This paper highlights some major pieces of research conducted by ARCPOH
      and demonstrates the application of that research to the extension of water
      fluoridation in Victoria.

PMID- 22998309
TI  - The future for oral health surveillance.
AB  - OBJECTIVES: To take an overview of the history and future of oral health
      surveillance. METHODS: A brief review of the history and policy context of
      national surveys and equivalent large surveys of oral health and their objectives
      followed by an analysis of their fitness for modern purpose. RESULTS AND
      CONCLUSION: The quality of oral health surveillance has improved immeasurably
      since the first attempts in the early 1960s, but national and regional surveys
      are still hampered by a lack of clarity about their purpose. The data they
      collect and describe are potentially invaluable and have the major advantages of
      being both robust and relatively straightforward to interpret and explain to
      policy makers. A greater clarity of purpose both from researchers and those who
      commission research would allow better use of data and a greater understanding of
      the limitations of surveillance. The international research community have a role
      to play in establishing and sharing best practice globally.

PMID- 22998310
TI  - Building the links between surveillance, research, and policy and practice-
      dental public health experiences in Australia.
AB  - OBJECTIVES: To identify how to translate dental public health surveillance and
      broader research into policy and practice. METHODS: Via a literature review to
      identify both the potential uses of surveillance data and key elements in the
      policy making process. Then through a consideration of Australian dental public
      health examples to identify ways to build links between this research and policy
      making. RESULTS: The development of dental public health policy can be complex.
      Different notions of evidence are held by researchers and policy makers. A
      cultural gap divides these two groups. Translation of research into policy is
      more likely if an issue is moved up the policy agenda through judicial
      articulation of the problem with an associated policy proposal and where
      political factors are positive. If these elements exist, a policy outcome is more
      possible when a 'policy window' opens. Five ways to build the links between
      surveillance, research and policy and practice are to communicate across the
      cultural gap; be prepared for chance opportunities to transfer knowledge;
      undertake policy relevant research; don't abuse research evidence by making
      exaggerated claims; and provide timely dissemination of surveillance and research
      findings. Structural barriers to academics having greater engagement with policy
      agencies also need to be addressed. CONCLUSION: Translating surveillance and
      broader research evidence into policy requires active management rather than
      expecting passive diffusion. Researchers need to understand and act on the
      external factors that are likely to affect the uptake of their research if they
      want their research to influence policy and practice.

PMID- 22998311
TI  - How population-level data linkage might impact on dental research.
AB  - There is the potential for substantial gains in dental epidemiology with
      increasing use of population-level data and data linkage. The advantage of
      population record linkage, from an epidemiological perspective, is that it is not
      biased and no-one is excluded. This has important implications for human rights
      because generally the people who are excluded from studies or do not participate
      are the most marginalized. There are a number of places in the world that have
      high-quality population record linkage in the area of health including Oxford,
      Aberdeen, Rochester, Manitoba and Scandinavia. In Western Australia, there is a
      unique set of databases on the entire population, which includes detailed
      information on all births, deaths and hospital admissions since 1980, these are
      linkable with many other data sets. We can now link birth and hospital admissions
      with population databases for characteristics such as intellectual disability and
      birth defects. It is even possible to link Commonwealth data with State data. It
      is now possible to link birth defects data and midwives data with data from the
      Commonwealth Pharmaceutical Benefits Scheme as a form of pharmacovigilance, to
      detect potential associations between medicine use in pregnancy and birth defects
      such as cleft lip and palate. Data linkage is increasingly available in
      Australia, with other states setting up systems similar to Western Australia and
      may offer greater insight into oral health.

PMID- 22998312
TI  - Measuring the oral health of populations.
AB  - OBJECTIVES: This article provides a conceptual base for population oral health
      measurement and argues that problems associated with particular indices are
      subject to the basic issues of knowing what to measure and the level of
      measurement required to address the object of study and provide clear information
      about the health of the population as a whole. METHODS: Alternative approaches to
      caries measurement are presented using data from South Australian children
      attending the school dental services during 2007. RESULTS: While threshold
      selection of case definitions depicted different profiles of the same population,
      the inclusion of non-cavitated lesions did not alter the general disease profile
      of the population. CONCLUSIONS: The types of measures used depend on the purpose,
      nature of the data, and conceptualization of the phenomenon, and should
      continually refer to the population level. In population oral health,
      controversies surrounding outcome measures, such as caries indices, are moving
      away from addressing core issues to narrowing mechanistic views. Fundamental
      deliberations should include the valuation of health states, clearly defining
      health and disease and distinguishing between disease, determinants and the
      impacts of disease.

PMID- 22998313
TI  - Reforming the mission of public dental services.
AB  - Australia has a complex history of providing public dental services to its
      communities. From the early days of Colonial settlement, the provision of dental
      care to the Australian public has largely been driven and influenced by organized
      groups and associations of dentists. The Constitution of Australia, under Section
      51 xxiii A, allows for the Commonwealth to provide for medical and dental
      services. Unlike the United Kingdom, however, dental services have not been
      embedded into a universal national health service agenda. In 1974, that the
      Australian Government through the Australian School Dental Program provided the
      first funding and national direction for public dental services - and that,
      limited to children. The Commonwealth Dental Health Program 1993-1997 was the
      second national endeavor to provide public dental services, this time to
      financially disadvantaged adults. Since that time, public dental service
      responsibility has been shuttled between States/Territories and the Commonwealth.
      A new paradigm for public dental services in Australia requires strong
      Commonwealth leadership, as well as the commitment of State and Territories and
      the organized dental profession. The National Health and Hospitals Reform
      Commission provided the most recent scenario for a radical change in mission.
      This paper canvases the competing roles of strategic, functional, and structural
      issues in relationship to social network and policy issues, which must be
      recognized if Australians truly seek to reform public dental services.

PMID- 22998314
TI  - Revolution in the provision of dental services in the UK.
AB  - The National Health Service (NHS) in England provides a comprehensive dental
      service funded largely from taxation but supplemented by co-payments. OBJECTIVES:
      This paper provides a historical overview of NHS dental services and some
      personal reflections on the main challenges over the next five years. METHODS: A
      narrative review of the literature and some subjective observations and comments.
      RESULTS: In 2006 there was a radical change to NHS dental services in England;
      central budgets were capped and general dental practitioners. Dentists who were
      previously paid on a fee-for-item basis moved to a new contract that required
      them to hit activity targets to maintain their historical income. This contract
      was unpopular with dentists and has been criticized for not improving access or
      quality. A new dental contract has been promised based on capitation. Against
      this background significant issues have to be addressed including: a rapidly
      growing gap in between demand and resources and a need to make substantial cost
      savings across the whole of the NHS; a significant decline in dental need;
      inequalities in utilisation of dental services; and provision of treatments of
      doubtful effectiveness. CONCLUSION: The NHS dental healthcare system faces
      significant challenges and consideration needs to be given to the consequences of
      a focus on need rather than demand. Logically this would require a needs-based
      resource allocation formula and a needs-based approach to service and workforce
      planning. A move to a needs-led service is a political decision with associated
      political risks.

PMID- 22998315
TI  - Economic evaluation of preventive dental programs: what can they tell us?
AB  - The role of public health program planners is to determine the effectiveness of
      public health programs, what recommendations should be made, what future
      initiatives should be taken, and what policies should be developed. At a basic
      level, to choose between competing alternatives, two characteristics of an
      intervention must be considered; these are its outcome and its cost. Based on
      cost and outcome, planners must select the option that offers the most
      advantages. Economic evaluation is commonly adopted by decision makers in the
      health sector to investigate the effectiveness of public health programs and to
      help plan future initiatives. Economic evaluation assists decision makers who
      must weigh the information it provides in the context of many and often competing
      options. In this way, an economic evaluation is an aid to decision making rather
      than the decision itself. Economic evaluation is becoming essential for informed
      decision making, with potential implications for public health policy and
      practice and for clinical practice too. While economic evaluations are commonly
      used in decision-making processes about health programs, few examples exist in
      the oral health literature. In the case of preventive oral health programs,
      economic analysis is often difficult, largely because it makes demands on
      epidemiological and demographic data that are hard to meet. This study will
      address the concepts and tools required to conduct economic evaluations of
      prevention programs. The emphasis will be on oral health and preventive dental
      programs, although the concepts presented could be useful for other public health
      programs by practitioners and managers with the aim of producing effective and
      efficient oral health programs.

PMID- 22998316
TI  - Shaping the next generation of 'population oral healthers'.
AB  - OBJECTIVE: The aim of this paper is to discuss the training and development needs
      of those people who will form the next generation working in the field of
      population oral health. METHOD: The paper represents the personal views of the
      author based upon an analysis of current training programmes in a number of
      countries and variation in the international working conditions. DISCUSSION: The
      next generation of population oral healthers will need to be versatile in their
      approach to the oral health problems they encounter. The simple problems may well
      have been solved or have stopped improving. The future generation will work in a
      variety of roles: commissioning and designing services, providing and evaluating
      services, educating or researching. The working environment will also show
      considerable variation and diversity from entirely private systems through mixed
      economies to public systems and, of course, no system at all. Current curricula
      vary but tends to emphasis traditional epidemiological and statistical skills as
      well as service delivery. There is also some evidence that training opportunities
      are limited to those with clinical backgrounds. Universities continue to emphasis
      high quality, high impact and high financial value research as they seek to
      maximize income and climb international league tables. National research funding
      bodies are seeking to address major issues such as global warming, food security
      and international security. Health research appears to have a number of foci:
      increasingly complex biomedical research, economic and effectiveness research and
      the complex questions around diseases of poverty and lifestyle. Access to funding
      will be increasingly competitive. CONCLUSIONS: The next generation will need to
      access and understand an increasing range of disciplines using a wide range of
      transferable and political skills as they work across a diverse range of social
      situations and disease states. A key issue will be the requirement for them to be
      adaptable and flexible as they work to improve oral health.

PMID- 22998317
TI  - Embedding a population oral health perspective in the dental curriculum.
AB  - Over the past 40 years, oral healthcare has changed dramatically as a consequence
      of changing disease profiles and population demography. However, dental disease
      continues to be highly prevalent and costly to treat. Furthermore, it has been
      recognized that there are inequalities, with tooth loss being influenced by
      social, cultural and economic factors. Undergraduate education has been task
      oriented, with a heavy emphasis on training in technical aspects of treating
      disease. However, oral healthcare education needs to include a population health
      perspective, and each professional programme should describe appropriate learning
      outcomes for population oral health. This includes the need to understand health
      systems and health trends, and to have knowledge of the evidence base for
      community prevention strategies and health promotion. A key challenge in
      embedding population oral health into the curriculum is to break down traditional
      boundaries in the curriculum and to make teaching of this subject context
      specific and interdisciplinary. Embedding population oral health offers the
      potential to create synergies between educators and health service providers with
      the ultimate benefit of producing a reflective and holistic oral health
      practitioner. There are challenges, but it is important to produce graduates
      whose attitudes and clinical practices will be shaped by a sound knowledge of
      population oral health.

PMID- 22998318
TI  - Transcultural dental training: addressing the oral health care needs of people
      from culturally diverse backgrounds.
AB  - Australia is a culturally and linguistically diverse country with a population
      derived from over 140 countries and including 240 language groups. Reflecting
      this, there has been a significant increase in cultural diversity among
      undergraduate dental students. It has been recognized that in order for dental
      students to interact and respond effectively to the diverse cultural needs of
      their patients, students themselves must be aware of cultural differences and
      respect patients' worldviews. In response to this challenge, dental students will
      need to have the theoretical knowledge to understand culturally-influenced health
      behaviours as well as the ability to communicate effectively with culturally
      diverse patients. Currently, the culture of dental students contrasts with the
      patients they treat, which may in turn affect the interaction between dental
      students and their patients. Given this context, new graduates need both to
      effectively communicate with patients from diverse communities and have an
      understanding of culturally influenced health behaviours. It has been proposed
      that dental graduates need to improve their knowledge of a variety of cultural
      values, beliefs, practices and attitudes. The literature in the area of cultural
      awareness and education for oral health professionals concentrates on both
      exploring health professionals' knowledge and attitudes toward transcultural care
      or the need for transcultural training. This paper provides an overview of the
      transcultural issues in oral health care which might confront dental students
      when treating culturally diverse patients. It will also discuss possible
      modifications to the dental curriculum to ensure that the future oral health
      workforce understands the complex health care needs of a multicultural society.
      This information will give planners and stakeholders an insight into the nature
      of the cultural issues which future dentists are likely to encounter while
      treating patients from diverse cultural backgrounds. This would help to establish
      the need to incorporate transcultural awareness modules to enhance quality of
      care and to respond effectively and sensitively to cultural issues.

PMID- 22998319
TI  - Envisioning an oral healthcare workforce for the future.
AB  - Health is critical to human well-being. Oral health is an integral component of
      health. One is not healthy without oral health. As health is essential to human
      flourishing, it is important that an oral healthcare delivery system and
      workforce be developed and deployed which can help ensure all citizens have the
      potential to access oral health care. As such access does not generally exist
      today, it is imperative to advance the realization of this goal and to develop a
      vision of an oral healthcare workforce to functionally support access. Public
      funding of basic oral health care is an important element to improving access.
      However, funding is only economically feasible if a workforce exists that is
      structured in a manner such that duties are assigned to individuals who have been
      uniquely trained to fulfill specific clinical responsibilities. An essential
      element of any cost-effective organizational system must be the shared
      responsibility of duties. Delegation must occur in the oral health workforce if
      competent, cost-effective care is to be provided. Desirable members of the oral
      health team in an efficient and effective system are as follows: generalist
      dentists who are educated as physicians of the stomatognathic system (oral
      physicians), specialist dentists, dental therapists, dental hygienists, dually
      trained hygienists/therapists (oral health therapists), oral prosthetists
      (denturists), and expanded function dental assistants (dental nurses).

PMID- 22998320
TI  - Influencing public policy on oral health.
AB  - OBJECTIVES: In policy studies, an enduring research question is why some issues
      are taken seriously while others never become a central focus of policy making.
      This study aims to analyse the predecision stage of policy making and examines
      the position of oral health on the broader health policy agenda. METHODS: A study
      of networks of influence in health policy in the state of Victoria (Australia) is
      used to examine the health policy agenda, and the position of oral health within
      the broader health policy agenda. Social network concepts were used to structure
      the data collection. Nominations of influential people were collected using a
      snowball method, followed by interviews with a selection of those nominated.
      RESULTS: Combining an assessment of who is seen to be influential with an
      examination of the issues they are interested in provides insights into how
      influence helps shape the policy agenda and how this changes over time.
      CONCLUSIONS: The study describes how oral health might become more central to the
      health policy agenda through deliberate strategies to change the network
      structure.

PMID- 22998321
TI  - Special issue: Festschrift in honour of John Spencer. Preface.

PMID- 22998322
TI  - Prospective observational study of dementia and delirium in the acute hospital
      setting.
AB  - BACKGROUND: Dementia and delirium appear to be common among older patients
      admitted to acute hospitals, although there are few Australian data regarding
      these important conditions. AIM: The aim of this study was to determine the
      prevalence and incidence of dementia and delirium among older patients admitted
      to acute hospitals in Queensland and to profile these patients. METHOD:
      Prospective observational cohort study (n = 493) of patients aged 70 years and
      older admitted to general medical, general surgical and orthopaedic wards of four
      acute hospitals in Queensland between 2008 and 2010. Trained research nurses
      completed comprehensive geriatric assessments and obtained detailed information
      about each patient's physical, cognitive and psychosocial functioning using the
      interRAI Acute Care and other standardised instruments. Nurses also visited
      patients daily to identify incident delirium. Two physicians independently
      reviewed patients' medical records and assessments to establish the diagnosis of
      dementia and/or delirium. RESULTS: Overall, 29.4% of patients (n = 145) were
      considered to have cognitive impairment, including 102 (20.7% of the total) who
      were considered to have dementia. This rate increased to 47.4% in the oldest
      patients (aged >= 90 years). The overall prevalence of delirium at admission was
      9.7% (23.5% in patients with dementia), and the rate of incident delirium was
      7.6% (14.7% in patients with dementia). CONCLUSION: The prevalence of dementia
      and delirium among older patients admitted to acute hospitals is high and is
      likely to increase with population aging. It is suggested that hospital design,
      staffing and processes should be attuned better to meet these patients' needs.

PMID- 22998323
TI  - Theoretical studies on the susceptibility of oseltamivir against variants of 2009
      A/H1N1 influenza neuraminidase.
AB  - The outbreak and high speed global spread of the new strain of influenza A/H1N1
      virus in 2009 posed a serious threat to global health. It is more likely that
      drug-resistant influenza strains will arise after the extensive use of anti
      influenza drugs. Consequently, the identification of the potential resistant
      sites for drugs in advance and the understanding of the corresponding molecular
      mechanisms that cause drug resistance are quite important in the design of new
      drug candidates with better potency to combat drug resistance. Here, we performed
      molecular simulations to evaluate the potency of oseltamivir to combat drug
      resistance caused by the mutations in 2009 A/H1N1 neuraminidase (NA). We examined
      three representative drug-resistant mutations in NA, consisting of H274Y, N294S,
      and Y252H. First, a theoretical structure of A/H1N1 NA in complex with
      oseltamivir was constructed using homology modeling. Then, molecular dynamics
      (MD) simulations, molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA)
      calculations, and MM/GBSA free energy decomposition were used to characterize the
      binding of oseltamivir with the wild type (WT) and three mutated NAs. Our
      predictions show that N294S and H274Y, two popular drug-resistant mutations in
      different variants of NA, still cause significant resistance to oseltamivir.
      However, the Y252H mutation does not impair the interactions between oseltamivir
      and A/H1N1 NA. An examination of individual energy components shows that the loss
      of polar interactions is the key source for the resistance of the studied
      mutations to oseltamivir. Moreover, free energy decomposition analysis and
      structural analysis reveal that the N294S or H274Y mutation triggers the large
      scale conformational changes of the binding pocket and then impairs the affinity
      of oseltamivir. We expect that our results will be useful for the rational design
      of NA inhibitors with high potency against drug-resistant A/H1N1 mutants.

PMID- 22998324
TI  - Patients who take their symptoms less seriously are more likely to have
      colorectal cancer.
AB  - BACKGROUND: People vary in how they respond to symptoms. The purpose of this
      study was to assess whether serious disease is more likely to be present in
      patients who report that they take any symptoms less seriously than other people
      do, and to assess the reliability of a question which can be used to identify the
      extent to which patients take any symptom seriously. To do this we assessed
      whether the likelihood of detecting colorectal cancer is higher in patients who
      report that they take symptoms less seriously than other people do. METHODS:
      Cross sectional study of 7736 patients who had colonoscopy to find colorectal
      cancer. Before colonoscopy, patients completed a questionnaire on bowel symptoms
      and were also asked: "Compared to other people of your age and sex, how seriously
      do you think you take any symptoms?" Likelihood of detecting colorectal cancer
      according to responses to this question was assessed by logistic regression
      models, unadjusted and adjusted for symptoms and other known predictors of
      colorectal cancer.Question reliability was assessed in a different sample using
      percentage agreement and the kappa statistic for the answers given by each
      patient on two occasions. Agreement between patient and doctor responses was also
      assessed (n = 108). RESULTS: Patients who reported they took symptoms less
      seriously were 3.28 (95%CI: 2.02, 5.33) times more likely to have colorectal
      cancer than patients who took symptoms more seriously than others. The effect was
      smaller (1.85 (95%CI: 1.11, 3.09)), but remained statistically significant in
      models including symptoms and other predictors of colorectal cancer. The question
      was reliable: on repeat questioning, 70% of responses were in absolute agreement
      and 92% were within 1 category, kappa 57%. Patient-doctor agreement was 66%,
      within 1 category 92%, kappa 48%. CONCLUSION: Patients who take their symptoms
      less seriously have a considerably higher likelihood of colorectal cancer than
      those who identify themselves as taking any symptoms more seriously than other
      people. The question is easy to ask and has good reliability. Doctors also
      reliably identify how patients assess themselves. Assessment of how seriously
      patients take any symptoms can contribute to the clinical assessment of a
      patient.

PMID- 22998326
TI  - Blood pressure, heart rate, and urinary catecholamines in healthy dogs subjected
      to different clinical settings.
AB  - BACKGROUND: Correct interpretation of blood pressure (BP) and heart rate (HR)
      recordings is important in a clinical environment, but little is known about
      effects of stress on BP and HR responses of dogs to different clinical settings.
      OBJECTIVE: To investigate BP and HR responses in different clinical settings in
      dogs of 3 breeds, and to relate findings to urinary catecholamine concentrations
      measured by ELISA assays previously validated for use in human plasma and urine,
      after validation for use in dogs. ANIMALS: Client-owned healthy dogs; 41 Labrador
      Retrievers, 33 Cavalier King Charles Spaniels (CKCS), and 15 Dachshunds. METHODS:
      Prospective observational study. BP and HR were measured in 4 clinical settings
      with or without veterinarian and owner present. Urine samples were taken before
      and after examination. ELISA assays were validated for canine urine, and
      epinephrine/creatinine and norepinephrine/creatinine ratios were analyzed.
      RESULTS: BP and HR were higher when measured by veterinarian alone than when
      owner was present (P < .020). Urinary catecholamine/creatinine ratios were higher
      after examination, compared with before, in all dogs (P < .0001). Labrador
      Retrievers had lower diastolic BP than Dachshunds in 2 settings (P <= .041),
      lower HR than CKCSs in 3 settings (all P < .0001), and lower
      catecholamine/creatinine ratios after examination than both other breeds (P <=
      .035). The in-house validation showed mean spiked recovery of 96.5% for
      epinephrine and 83.8% for norepinephrine. CONCLUSIONS AND CLINICAL IMPORTANCE: BP
      and HR responses were related to breed as well as clinical setting. Breed
      differences were detected in urinary catecholamine/creatinine ratios. Further
      studies on breed differences are warranted.

PMID- 22998327
TI  - Postoperative vomiting in pediatric oncologic patients: prediction by a fuzzy
      logic model.
AB  - OBJECTIVE: To report a fuzzy logic mathematical model to predict postoperative
      vomiting (POV) in pediatric oncologic patients and compare with preexisting
      scores. BACKGROUND: Although POV has a high incidence in children and may
      decrease parental satisfaction after surgeries, there is only one specific score
      that predicts POV in children: the Eberhart's score. In this study, we report a
      fuzzy model that intends to predict the probability of POV in pediatric oncologic
      patients. Fuzzy logic is a mathematical theory that recognizes more than simple
      true and false values and takes into account levels of continuous variables such
      as age or duration of the surgery. The fuzzy model tries to account for
      subjectiveness in the variables. METHODS: Preoperative potential risk factors for
      POV in 198 children (0-19 year old) with malignancies were collected and
      analyzed. Data analysis was performed with the chi-square test and logistic
      regression to evaluate probable risk factors for POV. A system based on fuzzy
      logic was developed with the risk factors found in the logistic regression, and a
      computational interface was created to calculate the probability of POV. RESULTS:
      The model showed a good performance in predicting POV. After the analysis, the
      model was compared with Eberhart's score in the same population and showed a
      better performance. CONCLUSIONS: The fuzzy score can predict the chance of POV in
      children with cancer with good accuracy, allowing better planning for
      postoperative prophylaxis of vomiting. The computational interface is available
      for free download at the internet and is very easy to use.

PMID- 22998325
TI  - Fractional anisotropy distributions in 2- to 6-year-old children with autism.
AB  - BACKGROUND: Increasing evidence suggests that autism is a disorder of distributed
      neural networks that may exhibit abnormal developmental trajectories.
      Characterisation of white matter early in the developmental course of the
      disorder is critical to understanding these aberrant trajectories. METHODS: A
      cross-sectional study of 2- to 6-year-old children with autism was conducted
      using diffusion tensor imaging combined with a novel statistical approach
      employing fractional anisotropy distributions. Fifty-eight children aged 18-79
      months were imaged: 33 were diagnosed with autism, 8 with general developmental
      delay, and 17 were typically developing. Fractional anisotropy values within
      global white matter, cortical lobes and the cerebellum were measured and
      transformed to random F distributions for each subject. Each distribution of
      values for a region was summarised by estimating delta, the estimated mean and
      standard deviation of the approximating F for each distribution. RESULTS: The
      estimated delta parameter, , was significantly decreased in individuals with
      autism compared to the combined control group. This was true in all cortical
      lobes, as well as in the cerebellum, but differences were most robust in the
      temporal lobe. Predicted developmental trajectories of across the age range in
      the sample showed patterns that partially distinguished the groups. Exploratory
      analyses suggested that the variability, rather than the central tendency,
      component of was the driving force behind these results. CONCLUSIONS: While
      preliminary, our results suggest white matter in young children with autism may
      be abnormally homogeneous, which may reflect poorly organised or differentiated
      pathways, particularly in the temporal lobe, which is important for social and
      emotional cognition.

PMID- 22998328
TI  - Diabetes and health outcomes among older Taiwanese with hip fracture.
AB  - OBJECTIVE: Hip fracture tremendously impacts functional abilities for the elderly
      with high morbidity and mortality; recovery is compromised by co-morbidities.
      Diabetes mellitus is a common co-morbidity for the aging population, but little
      is known about the influence of diabetes on outcomes of the Asian elderly with
      hip fracture. RESEARCH DESIGN AND METHODS: This study was a secondary analysis of
      data on 242 community-dwelling elders with hip fracture from three previous
      longitudinal studies. Sixty-one cases (25.2%) had diabetes. Outcomes were
      measured by the Chinese Barthel Index, Medical Outcomes Study Short Form-36
      Taiwan version, and analyzed by the generalized estimating equation approach to
      examine how diabetes influenced hip-fractured elders' mortality, service
      utilization, mobility, daily activities, and health-related quality of life
      during the first 12 months after postsurgical discharge in Taiwan. RESULTS: Hip
      fractured elderly with diabetes had a significantly higher mortality rate (22.6%
      vs. 10.3%, p=0.03) during the first year following discharge, and significantly
      higher readmission rate (10.0% vs. 2.5%, p=0.04) from the first to third month
      following discharge than those without diabetes. After controlling for
      covariates, elderly participants without diabetes had an overall 2.2 times
      (confidence interval [CI]=1.15-4.21) greater odds of recovery in walking ability
      and better reported general health (beta=9.33; p=0.01) and physical functioning
      (beta=7.26; p=0.02) than those with diabetes during the first year after
      discharge. CONCLUSIONS: Diabetes negatively influenced outcomes of elderly
      patients with hip fracture. The results may provide a reference for developing
      interventions for hip-fractured elders with diabetes.

PMID- 22998330
TI  - Severe infliximab-induced psoriasis treated with adalimumab switching.
AB  - BACKGROUND: Antitumor necrosis factor (anti-TNF) agents are a well-established
      treatment for various medical conditions, including psoriasis and psoriatic
      arthritis. However, anti-TNF agents may themselves induce psoriasis in some
      patients. METHODS: The authors report two cases of patients with severe and
      refractory infliximab-induced psoriasis. RESULTS: The patients had good clinical
      responses after switching to another TNF blocker. CONCLUSION: For severe cases,
      infliximab withdrawal combined with conventional immunosuppressive psoriasis
      drugs or with adalimumab may be a therapeutic option.

PMID- 22998329
TI  - Inflammation, adiposity, and mortality in the oldest old.
AB  - BACKGROUND: Increased proinflammatory status is associated with both increased
      adiposity and higher mortality risk. Thus, it is paradoxical that mild obesity
      does not predict increased mortality in older adults. We investigated the
      association of inflammatory markers with body mass index (BMI), waist
      circumference (WC), and waist-to-hip ratio (WHR) in nonagenarians, and the
      combined effects of BMI, WC, WHR, and inflammatory status on mortality. METHODS:
      This study was based on a prospective population-based study, Vitality 90+,
      carried out in Tampere, Finland. Altogether, 157 women and 53 men aged 90 years
      were subjected to anthropometric measurements, blood samples, and a 4-year
      mortality follow-up. Inflammatory status was based on sex-specific median levels
      of interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), C-reactive
      protein (CRP), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: In the
      unadjusted linear regression analyses, IL-1RA, CRP, and TNF-alpha were positively
      associated with BMI and WC in women, whereas in men IL-1RA was positively
      associated with BMI and IL-6 positively with WC. In the models adjusted for
      diseases, functional status, and smoking, IL-1RA and CRP were positively
      associated with BMI and WC in women. Low WC and WHR combined with low
      inflammation protected from mortality in women and high BMI and WC regardless of
      inflammation protected from mortality in men in the adjusted Cox regression
      analysis. CONCLUSIONS: In the oldest old, the effect of adiposity in combination
      with inflammatory status on mortality differs between men and women. More
      research is needed to disentangle the role of adiposity among the oldest old.

PMID- 22998331
TI  - Anatomical expression patterns of delta-protocadherins in developing chicken
      cochlea.
AB  - The delta-protocadherin (delta-Pcdh) family of transmembrane proteins belongs to
      the cadherin superfamily, which is involved in embryogenesis mediated by a
      homophilic binding during the embryonic development. In the present study,
      expression patterns of eight members of the delta-Pcdh family were investigated
      in the developing chicken cochlea by in situ hybridization. Our results provide a
      dynamical profile to show that the delta-Pcdhs are expressed spatially and
      temporally in the developing chicken cochleae. The earliest onset of the delta
      Pcdh expression begins in the otic vesicle from embryonic incubation day (E) 3.
      From E11 onwards, the individual delta-Pcdh is expressed in different cell types
      of the cochlea. Protocadherin-1 (Pcdh1) is mainly expressed by spindle-shaped
      cells and acoustic ganglion cells; Pcdh7 and Pcdh17 are strongly expressed by
      supporting cells, cuboidal cells, hyaline cells and acoustic ganglion cells, and
      Pcdh9 is prominently expressed by homogene cells and acoustic ganglion cells;
      Pcdh8 was found to be transcribed in hair cells, spindle-shaped cells and
      acoustic ganglion cells; Pcdh10 mRNA is restricted to spindle-shaped cells and
      acoustic ganglion cells at later stages. mRNAs of Pcdh1, Pcdh18 and Pcdh19 are
      also expressed in blood vessels of the cochlea. The expression of the different
      delta-Pcdhs suggests a functional role for them during cochlear development.

PMID- 22998332
TI  - Superacid-promoted ionization of alkanes without carbonium ion formation: a
      density functional theory study.
AB  - The carbonium ion has been suggested to be the intermediate in superacid-promoted
      reactions (SbF(5)-HF) such as hydrogen-deuterium exchange and in the
      electrophilic C-H cleavage into hydrogen and the carbenium ion. In this study,
      the superacid-promoted C-H cleavage into hydrogen and the carbenium ion was
      studied using density functional theory (B3LYP and M062X) and ab initio methods
      (MP2 and CCSD). The calculations suggest that the superacid-promoted C-H cleavage
      proceeds via a concerted transition state leading to hydrogen (H(2)) and the
      carbenium ion without the formation of the elusive carbonium ion. The reactivity
      for the superacid-promoted C-H cleavage decreases upon going from isobutane
      (tertiary) > propane (secondary) > isobutane (primary) > propane (primary) >
      ethane >> methane.

PMID- 22998333
TI  - Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and
      subcutaneous buprenorphine in conscious cats.
AB  - OBJECTIVE: To describe simultaneous pharmacokinetics (PK) and thermal
      antinociception after intravenous (i.v.), intramuscular (i.m.) and subcutaneous
      (SC) buprenorphine in cats. STUDY DESIGN: Randomized, prospective, blinded, three
      period crossover experiment. ANIMALS: Six healthy adult cats weighing 4.1+/-0.5
      kg. METHODS: Buprenorphine (0.02 mg kg(-1)) was administered i.v., i.m. or s.c..
      Thermal threshold (TT) testing and blood collection were conducted simultaneously
      at baseline and at predetermined time points up to 24 hours after administration.
      Buprenorphine plasma concentrations were determined by liquid chromatography
      tandem mass spectrometry. TT was analyzed using anova (p<0.05). A pharmacokinetic
      pharmacodynamic (PK-PD) model of the i.v. data was described using a model
      combining biophase equilibration and receptor association-dissociation kinetics.
      RESULTS: TT increased above baseline from 15 to 480 minutes and at 30 and 60
      minutes after i.v. and i.m. administration, respectively (p<0.05). Maximum
      increase in TT (mean+/-SD) was 9.3+/-4.9 degrees C at 60 minutes (i.v.), 4.6+/
      2.8 degrees C at 45 minutes (i.m.) and 1.9+/-1.9 degrees C at 60 minutes (s.c.).
      TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60
      and 120 minutes after i.v. administration compared to i.m. and s.c.,
      respectively. I.v. and i.m. buprenorphine concentration-time data decreased
      curvilinearly. S.c. PK could not be modeled due to erratic absorption and
      disposition. I.v. buprenorphine disposition was similar to published data. The PK
      PD model showed an onset delay mainly attributable to slow biophase equilibration
      (t(1/2) k(e0)=47.4 minutes) and receptor binding (k(on)=0.011 mL ng(-1) minute(
      1)). Persistence of thermal antinociception was due to slow receptor dissociation
      (t(1/2) k(off)=18.2 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: I.v. and i.m.
      data followed classical disposition and elimination in most cats. Plasma
      concentrations after i.v. administration were associated with antinociceptive
      effect in a PK-PD model including negative hysteresis. At the doses administered,
      the i.v. route should be preferred over the i.m. and s.c. routes when
      buprenorphine is administered to cats.

PMID- 22998334
TI  - Can diabetes prevention programmes be translated effectively into real-world
      settings and still deliver improved outcomes? A synthesis of evidence.
AB  - OBJECTIVE: Randomized trials provide evidence that intensive lifestyle
      interventions leading to dietary and physical activity change can delay or
      prevent Type 2 diabetes. Translational studies have assessed the impact of
      interventions based on, but less intensive than, trial protocols delivered in
      community settings with high-risk populations. The aim of this review was to
      synthesize evidence from translational studies of any design to assess the impact
      of interventions delivered outside large randomized trials. METHODS: Medical and
      scientific databases were searched using specified inclusion and exclusion
      criteria. Studies were included that used a tested diabetes preventive study
      protocol with an adult population at risk from Type 2 diabetes. Included papers
      were quality assessed and data extracted using recommended methods. RESULTS: From
      an initial 793 papers, 19 papers reporting 17 studies were included.
      Translational studies from a range of settings utilized a variety of methods. All
      were based on the US Diabetes Prevention Programme protocol or the Finnish
      Diabetes Prevention Study, with modifications that increased feasibility and
      access. The main outcome that was reported in all studies was weight change.
      Weight loss, which occurred in all but one study, was greater in intervention
      arms than in control subjects. No consistent differences were found in blood
      glucose or waist circumference. CONCLUSIONS: Translational studies based on the
      intensive diabetes prevention programmes showed that there is potential for less
      intensive interventions both to be feasible and to have an impact on future
      progression to diabetes in at-risk individuals.

PMID- 22998335
TI  - Persistent pelvic pain: rising to the challenge.
AB  - Persistent pelvic pain is a common condition, with up to 20% of those affected
      reporting severe pain. Once end organ disease has been assessed, further
      investigations should be minimised. Persistent pelvic pain as a hyperalgesic
      neuropathic pain condition must be considered in the differential diagnosis. A
      multidisciplinary assessment and management plan, prepared by the co-ordinating
      gynaecologist in consultation with the general practitioner, physiotherapist and
      psychologist (with gastroenterological, urological and pain medicine specialist
      input as deemed appropriate), is strongly recommended.

PMID- 22998336
TI  - Rhodium-catalyzed asymmetric synthesis of silicon-stereogenic dibenzooxasilines
      via enantioselective transmetalation.
AB  - A rhodium-catalyzed asymmetric synthesis of silicon-stereogenic dibenzooxasilines
      has been developed. High enantioselectivities have been achieved by employing
      (S,S)-Me-Duphos as the ligand through "enantioselective transmetalation".

PMID- 22998337
TI  - Nurse-based antenatal and child health care in rural India, implementation and
      effects - an Indian-Swedish collaboration.
AB  - INTRODUCTION: Improving maternal and child health care are two of the Millennium
      Development Goals of the World Health Organization. India is one of the countries
      worldwide most burdened by maternal and child deaths. The aim of the study was to
      describe how families participate in nurse-based antenatal and child health care,
      and the effect of this in relation to referrals to specialist care, institutional
      deliveries and mortality. METHODS: The intervention took place in a remote rural
      area in India and was influenced by Swedish nurse-based health care. A baseline
      survey was performed before the intervention commenced. The intervention included
      education program for staff members with a model called Training of Trainers and
      the establishment of clinics as both primary health centers and mobile clinics.
      Health records and manuals, and informational and educational materials were
      produced and the clinics were equipped with easily handled instruments. The study
      period was between 2006 and 2009. Data were collected from antenatal care and
      child healthcare records. The Chi-square test was used to analyze mortality
      differences between years. A focus group discussion and a content analysis were
      performed. RESULTS: Families' participation increased which led to more check-ups
      of pregnant women and small children. Antenatal visits before 16 weeks among
      pregnant women increased from 32 to 62% during the period. Women having at least
      three check-ups during pregnancy increased from 30 to 60%. Maternal mortality
      decreased from 478 to 121 per 100 000 live births. The total numbers of children
      examined in the project increased from approximately 6000 to 18 500 children.
      Infant mortality decreased from 80 to 43 per 1000 live births. Women and children
      referred to specialist care increased considerably and institutional deliveries
      increased from 47 to 74%. CONCLUSION: These results suggest that it is possible
      in a rural and remote area to influence peoples' awareness of the value of
      preventive health care. The results also indicate that this might decrease
      maternal and child mortality. The education led to a more patient-friendly
      encounter between health professionals and patients.

PMID- 22998338
TI  - Sugar-sweetened beverages and genetic risk of obesity.
AB  - BACKGROUND: Temporal increases in the consumption of sugar-sweetened beverages
      have paralleled the rise in obesity prevalence, but whether the intake of such
      beverages interacts with the genetic predisposition to adiposity is unknown.
      METHODS: We analyzed the interaction between genetic predisposition and the
      intake of sugar-sweetened beverages in relation to body-mass index (BMI; the
      weight in kilograms divided by the square of the height in meters) and obesity
      risk in 6934 women from the Nurses' Health Study (NHS) and in 4423 men from the
      Health Professionals Follow-up Study (HPFS) and also in a replication cohort of
      21,740 women from the Women's Genome Health Study (WGHS). The genetic
      predisposition score was calculated on the basis of 32 BMI-associated loci. The
      intake of sugar-sweetened beverages was examined prospectively in relation to
      BMI. RESULTS: In the NHS and HPFS cohorts, the genetic association with BMI was
      stronger among participants with higher intake of sugar-sweetened beverages than
      among those with lower intake. In the combined cohorts, the increases in BMI per
      increment of 10 risk alleles were 1.00 for an intake of less than one serving per
      month, 1.12 for one to four servings per month, 1.38 for two to six servings per
      week, and 1.78 for one or more servings per day (P<0.001 for interaction). For
      the same categories of intake, the relative risks of incident obesity per
      increment of 10 risk alleles were 1.19 (95% confidence interval [CI], 0.90 to
      1.59), 1.67 (95% CI, 1.28 to 2.16), 1.58 (95% CI, 1.01 to 2.47), and 5.06 (95%
      CI, 1.66 to 15.5) (P=0.02 for interaction). In the WGHS cohort, the increases in
      BMI per increment of 10 risk alleles were 1.39, 1.64, 1.90, and 2.53 across the
      four categories of intake (P=0.001 for interaction); the relative risks for
      incident obesity were 1.40 (95% CI, 1.19 to 1.64), 1.50 (95% CI, 1.16 to 1.93),
      1.54 (95% CI, 1.21 to 1.94), and 3.16 (95% CI, 2.03 to 4.92), respectively
      (P=0.007 for interaction). CONCLUSIONS: The genetic association with adiposity
      appeared to be more pronounced with greater intake of sugar-sweetened beverages.
      (Funded by the National Institutes of Health and others.).

PMID- 22998339
TI  - A randomized trial of sugar-sweetened beverages and adolescent body weight.
AB  - BACKGROUND: Consumption of sugar-sweetened beverages may cause excessive weight
      gain. We aimed to assess the effect on weight gain of an intervention that
      included the provision of noncaloric beverages at home for overweight and obese
      adolescents. METHODS: We randomly assigned 224 overweight and obese adolescents
      who regularly consumed sugar-sweetened beverages to experimental and control
      groups. The experimental group received a 1-year intervention designed to
      decrease consumption of sugar-sweetened beverages, with follow-up for an
      additional year without intervention. We hypothesized that the experimental group
      would gain weight at a slower rate than the control group. RESULTS: Retention
      rates were 97% at 1 year and 93% at 2 years. Reported consumption of sugar
      sweetened beverages was similar at baseline in the experimental and control
      groups (1.7 servings per day), declined to nearly 0 in the experimental group at
      1 year, and remained lower in the experimental group than in the control group at
      2 years. The primary outcome, the change in mean body-mass index (BMI, the weight
      in kilograms divided by the square of the height in meters) at 2 years, did not
      differ significantly between the two groups (change in experimental group minus
      change in control group, -0.3; P=0.46). At 1 year, however, there were
      significant between-group differences for changes in BMI (-0.57, P=0.045) and
      weight (-1.9 kg, P=0.04). We found evidence of effect modification according to
      ethnic group at 1 year (P=0.04) and 2 years (P=0.01). In a prespecified analysis
      according to ethnic group, among Hispanic participants (27 in the experimental
      group and 19 in the control group), there was a significant between-group
      difference in the change in BMI at 1 year (-1.79, P=0.007) and 2 years (-2.35,
      P=0.01), but not among non-Hispanic participants (P>0.35 at years 1 and 2). The
      change in body fat as a percentage of total weight did not differ significantly
      between groups at 2 years (-0.5%, P=0.40). There were no adverse events related
      to study participation. CONCLUSIONS: Among overweight and obese adolescents, the
      increase in BMI was smaller in the experimental group than in the control group
      after a 1-year intervention designed to reduce consumption of sugar-sweetened
      beverages, but not at the 2-year follow-up (the prespecified primary outcome).
      (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases
      and others; ClinicalTrials.gov number, NCT00381160.).

PMID- 22998340
TI  - A trial of sugar-free or sugar-sweetened beverages and body weight in children.
AB  - BACKGROUND: The consumption of beverages that contain sugar is associated with
      overweight, possibly because liquid sugars do not lead to a sense of satiety, so
      the consumption of other foods is not reduced. However, data are lacking to show
      that the replacement of sugar-containing beverages with noncaloric beverages
      diminishes weight gain. METHODS: We conducted an 18-month trial involving 641
      primarily normal-weight children from 4 years 10 months to 11 years 11 months of
      age. Participants were randomly assigned to receive 250 ml (8 oz) per day of a
      sugar-free, artificially sweetened beverage (sugar-free group) or a similar sugar
      containing beverage that provided 104 kcal (sugar group). Beverages were
      distributed through schools. At 18 months, 26% of the children had stopped
      consuming the beverages; the data from children who did not complete the study
      were imputed. RESULTS: The z score for the body-mass index (BMI, the weight in
      kilograms divided by the square of the height in meters) increased on average by
      0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group;
      the 95% confidence interval (CI) of the difference was -0.21 to -0.05. Weight
      increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the
      sugar group (95% CI for the difference, -1.54 to -0.48). The skinfold-thickness
      measurements, waist-to-height ratio, and fat mass also increased significantly
      less in the sugar-free group. Adverse events were minor. When we combined
      measurements at 18 months in 136 children who had discontinued the study with
      those in 477 children who completed the study, the BMI z score increased by 0.06
      SD units in the sugar-free group and by 0.12 SD units in the sugar group
      (P=0.06). CONCLUSIONS: Masked replacement of sugar-containing beverages with
      noncaloric beverages reduced weight gain and fat accumulation in normal-weight
      children. (Funded by the Netherlands Organization for Health Research and
      Development and others; DRINK ClinicalTrials.gov number, NCT00893529.).

PMID- 22998341
TI  - Calories from soft drinks--do they matter?

PMID- 22998342
TI  - Clinical decisions. Regulation of sugar-sweetened beverages.

PMID- 22998343
TI  - Portion sizes and beyond--government's legal authority to regulate food-industry
      practices.

PMID- 22998344
TI  - Supramolecular host-guest interactions of oxazine-1 dye with beta- and gamma
      cyclodextrins: a photophysical and quantum chemical study.
AB  - Supramolecular host-guest interactions of oxazine-1 dye with beta- and gamma
      cyclodextrins (betaCD and gammaCD, respectively) have been investigated in
      neutral aqueous solution (pH ~ 7) at ambient temperature (~25  degrees C)
      following absorption, fluorescence, and circular dichroism measurements. The dye
      forms inclusion complexes with both CDs, causing significant changes in its
      photophysical properties. Whereas fluorescence titration data for lower dye
      concentrations fit well with 1:1 stoichiometric complexes, the time-resolved
      fluorescence results indicate formation of a small extent of 1:2 (dye-host)
      complexes as well, especially at higher CD concentrations. The moderate range of
      the binding constant values for the present systems indicates the weaker
      hydrophobic interaction as responsible for the inclusion complex formation in
      these systems. It has also been observed that gammaCD facilitates dimerization of
      the dye, prominently indicated at the higher dye concentrations. On the contrary,
      betaCD always assists deaggregation of the dye, even at very high dye
      concentrations. Time-resolved fluorescence anisotropy results qualitatively
      support the inclusion complex formation in the present systems. Results from
      quantum chemical calculations also nicely corroborate with the inferences drawn
      from photophysical studies. Observed results demonstrate that the size
      compatibility of the guest and the host cavity mainly determines the host-guest
      interaction in the present systems, much similar to the substrate-catalyst
      binding in many biological systems.

PMID- 22998345
TI  - Predictors of tetrabromobisphenol-A (TBBP-A) and hexabromocyclododecanes (HBCD)
      in milk from Boston mothers.
AB  - Tetrabromobisphenol-A (TBBP-A) and hexabromocyclododecanes (HBCDs) are brominated
      flame retardants that have been found in human milk and serum throughout the
      world, but have received comparatively little attention in the United States. The
      objective of this study is to determine concentrations of these analytes in
      samples of breast milk collected from first-time mothers in the Greater Boston,
      Massachusetts area and to explore predictors of exposure. Human milk samples were
      analyzed by LC-ESI-MS/MS for TBBP-A, HBCDs (the alpha, beta, and gamma
      diastereomers), and HBCD degradation products: pentabromocyclododecanes (PBCDs)
      and tetrabromocyclododecadienes (TBCDs). HBCD diastereomers were detected in all
      samples with alpha-HBCD present in the highest proportion. TBBP-A, PBCDs, and
      TBCDs were detected in 35%, 42%, and 56% of the analyzed samples, respectively.
      Self-reported demographic, dietary and behavioral data were examined as
      predictors of HBCD levels. Levels of HBCD were significantly, positively
      associated with the number of stereo and video electronics in the home (17%
      increase/item; 95% Confidence Interval (CI) = 4-31%) and reduced in participants
      who regularly chose organic foods compared to those who did not (0.51, 95% CI =
      0.32-0.82). These results suggest that lifestyle factors are related to body
      burdens of HBCD and that domestic electronics may be an important source of HBCD
      exposure in the indoor environment.

PMID- 22998346
TI  - Enhanced function of redirected human T cells expressing linker for activation of
      T cells that is resistant to ubiquitylation.
AB  - It is likely that the enhancement of signaling after antigenic stimulation,
      particularly in the tumor microenvironment, would improve the function of
      adoptively transferred T cells. Linker for activation of T cells (LAT) plays a
      central role in T cell activation. We hypothesized that the ubiquitylation
      resistant form of LAT in cells would enhance T cell signaling and thus augment
      antitumor activity. To test this, human CD4(+) or CD8(+) T cells were
      electroporated with small interfering RNA (siRNA) to repress endogenous LAT and
      ubiquitylation-resistant LAT 2KR or wild-type LAT mRNA was introduced for
      reexpression. Significantly enhanced phosphorylation of LAT and phospholipase C
      gamma (PLCgamma) was observed, and augmented calcium signaling after T cell
      receptor (TCR) triggering was observed in LAT 2KR-expressing T cells. TCR-induced
      calcium signaling was abrogated in LAT knockdown cells, but the baseline was
      higher than that of control siRNA-electroporated cells, suggesting a fundamental
      requirement of LAT to maintain calcium homeostasis. Redirected LAT 2KR T cells
      expressing a chimeric antigen receptor or an MHC class I-restricted TCR showed
      augmented function as assessed by enhanced cytokine secretion and cytotoxicity.
      These results indicate that interruption of LAT ubiquitylation is a promising
      strategy to augment effector T cell function for adoptive cell therapy.

PMID- 22998347
TI  - The evaluation of apomorphine for the treatment of erectile dysfunction.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common condition affecting men.
      Apomorphine is one of the oral medications that has been used in the management
      of ED, though over recent years, its use in the management of ED has dwindled.
      AREAS COVERED: The authors review the evidence available for the use of
      apomorphine in the management of ED. A Medline search was performed searching for
      the articles related to the use of apomorphine in the treatment of ED from 2000
      to present. The article reviews the erectogenic properties of apomorphine and
      evaluates its efficacy, suitability and tolerability in management of patients
      with ED. EXPERT OPINION: Apomorphine SL is more effective than placebos in
      treating ED and is generally well tolerated in the sublingual formulation,
      causing tolerable side effects. Newer nasal-spray formulations provide faster
      efficacy. Its efficacy in patients with multiple co-morbidities is more limited.
      However, it is not as effective as PDE5-I in the treatment of ED. Its most
      significant strength is its safety profile. It may have a niche in the treatment
      ED in patients who have failed treatment with, or are intolerant to other well
      established pharmacological treatment for ED (e.g., PDE5-Is). Apomorphine is not
      a first-line treatment option for patients with ED, especially as it is no more
      widely available in the western world.

PMID- 22998349
TI  - The effect of a familiarisation period on subsequent strength gain.
AB  - Untrained subjects can display diverse strength gain following an identical
      period of resistance exercise. In this investigation, 28 untrained males
      completed 16-weeks of resistance exercise, comprising 4-weeks familiarisation,
      and 12-weeks of heavy-load (80-85%) activity. High and low responders were
      identified by the Delta1RM (Delta one repetition maximum) observed following
      familiarisation (25.1 +/- 1.4%, 9.5 +/- 1.4%, P < 0.0001) and differences in
      electromyographic root mean square amplitude (DeltaEMG(RMS) 29.5 +/- 8.3%, 2.4 +/
      6.0%, P = 0.0140), and habitual and occupational activity patterns were observed
      between these respective groups. The strength gain (P < 0.0001) observed within
      high (29.6 +/- 1.7%) and low (31.4 +/- 2.7%) responding groups was similar during
      the heavy-load phase, yet DeltaEMG(RMS) increased (P = 0.0048) only in low
      responders (31.5 +/- 9.3%). Retrospectively, differences (P < 0.0001) in baseline
      1RM strength of high- (19.7 +/- 0.9 kg) and low-responding (15.6 +/- 0.7 kg)
      groups were identified, and a strong negative correlation with Delta1RM after 16
      weeks (r (2 )= -0.85) was observed. As such, baseline 1RM strength provided a
      strong predicative measure of strength adaptation. The DeltaEMG(RMS) suggests
      strength variability within high and low responders may be attributed to neural
      adaptation. However, differences in habitual endurance and occupational physical
      activity suggests one should consider screening not only recent resistance
      training, but also other modes of physical activity during participant
      recruitment.

PMID- 22998348
TI  - Legionella pneumophila infection presenting as headache, confusion and dysarthria
      in a human immunodeficiency virus-1 (HIV-1) positive patient: case report.
AB  - BACKGROUND: Legionella pneumophila is a common cause of community-acquired
      pneumonia. Central nervous system dysfunction is common, and diagnosis in the
      absence of pulmonary symptoms can be challenging. Here we describe an atypical
      clinical presentation of Legionella infection in a patient with HIV who was found
      to have an unusual neuroradiologic lesion that further served to obscure the
      diagnosis. This is the first such description in a patient with Legionellosis and
      HIV coinfection. CASE PRESENTATION: A 43 year-old HIV positive man presented to
      our hospital with dysarthria, fevers, headache, and altered mental status.
      Initial work-up revealed pneumonia and a lesion of the splenium of the corpus
      callosum on magnetic resonance imaging. He was subsequently diagnosed with
      Legionella pneumonia and treated with complete symptom resolution. CONCLUSIONS:
      Neurologic abnormalities are frequent in Legionellosis, but the diagnosis may be
      difficult in the absence of overt respiratory symptoms and in the presence of HIV
      coinfection. A high index of suspicion and early initiation of empiric
      antibiotics is imperative since early treatment may help prevent long-term
      sequelae. Neuroimaging abnormalities, though rare, can help the physician narrow
      down the diagnosis and avoid unnecessary invasive testing. Future studies should
      aim to elucidate the as yet unknown role of neuroimaging in the diagnoses and
      prognostication of Legionellosis, as well as the interaction between Legionella
      infection and HIV.

PMID- 22998350
TI  - A double-edged sword with therapeutic potential: an updated role of autophagy in
      ischemic cerebral injury.
AB  - Cerebral ischemia is a severe outcome that could cause cognitive and motor
      dysfunction, neurodegenerative diseases and even acute death. Although the
      existence of autophagy in cerebral ischemia is undisputable, the consensus has
      not yet been reached regarding the exact functions and influence of autophagy in
      cerebral ischemia. Whether the activation of autophagy is beneficial or harmful
      in cerebral ischemia injury largely depends on the balance between the burden of
      intracellular substrate targeted for autophagy and the capacity of the cellular
      autophagic machinery. Furthermore, the mechanisms underlying the autophagy in
      cerebral ischemia are far from clear yet. This brief review focuses on not only
      the current understanding of biological effects of autophagy, but also the
      therapeutic potentials of autophagy in ischemic stroke. There are disputes over
      the exact role of autophagy in cerebral ischemia. Application of chemical
      autophagy inhibitor (e.g., 3-methyladenine) or inducer (e.g., rapamycin) in vitro
      and in vivo was reported to protect or harm neuronal cell. Knockdown of
      autophagic protein, such as Beclin 1, was also reported to modulate the cerebral
      ischemia-induced injury. Moreover, autophagy inhibitor abolished the
      neuroprotection of ischemic preconditioning, implying a neuroprotective effect of
      autophagy. To clarify these issues on autophagy in cerebral ischemia, future
      investigations are warranted.

PMID- 22998351
TI  - Effect of congenital heart defects on language development in toddlers with Down
      syndrome.
AB  - BACKGROUND: Down syndrome (DS, OMIM #190685) is the most commonly identified
      genetic form of intellectual disability with congenital heart defect (CHD)
      occurring in 50% of cases. With advances in surgical techniques and an increasing
      lifespan, this has necessitated a greater understanding of the neurodevelopmental
      consequences of CHDs. Herein, we explore the impact of CHD on language
      development in children with DS. METHODS: Twenty-nine children with DS were
      observed systematically in parent-child interactions using the Communication Play
      Protocol to evaluate their language use; they also completed the Mullen Scales of
      Early Learning and MacArthur Communication Development Inventory. Mean ages were
      31.2 months for children with DS and CHD (DS + CHD, n = 12) and 32.1 months for
      children with DS and a structurally normal heart (DS - CHD, n = 17). RESULTS:
      Compared with the DS - CHD controls, the DS + CHD group revealed lower scores in
      multiple areas, including fine motor skills and expressive and receptive
      vocabulary. Whereas most differences were not statistically significant, the
      Communication Development Inventory word count and symbol-infused joint
      engagement differed significantly (P < 0.01) and marginally (P = 0.09) between
      groups. CONCLUSIONS: Finding that CHDs may account for part of the variation in
      language delay allows us to consider the specific mechanisms underlying the
      impact of CHDs on language acquisition in children with DS. Conclusions from this
      first study on early language outcomes of children with DS + CHD may be useful
      for clinicians in providing developmental surveillance and early intervention
      programmes with specific emphasis on language therapy as part of long-term follow
      up for children with DS + CHD.

PMID- 22998352
TI  - Shorter preparation to procedure interval for colonoscopy improves quality of
      bowel cleansing.
AB  - BACKGROUND: The timing of bowel preparation for colonoscopy influences the
      quality of bowel cleansing and the success of the procedure. AIM: We aimed to
      determine whether the interval between the end of bowel preparation and the start
      of colonoscopy influences preparation quality. METHODS: We retrospectively
      analysed 1785 colonoscopies performed between January 2010 and January 2011. The
      quality of bowel cleansing was compared between those who had a less than 8-h
      interval between the end of bowel preparation to the start of the procedure
      versus those who had a greater than 8-h interval. Univariate and multivariate
      logistic regression analyses evaluated quality of bowel cleansing, preparation to
      procedure time, age, gender, hospital inpatient or outpatient status, indication
      for colonoscopy, caecal intubation rate, and segmental polyp detection. RESULTS:
      Fifty-three per cent of the cohort was male. Eighty-nine per cent were
      outpatients. Bowel cleansing was reported as satisfactory/good in 87% and poor in
      13%. A <8-h preparation to procedure time was associated with a higher rate of
      satisfactory/good cleansing than a >8-h interval (odds ratio (OR) 1.3, P = 0.04).
      In a multivariate analysis, female gender (OR 1.4, P = 0.02), outpatient status
      (OR 3.1 P = 0.001) and indication for procedure (P < 0.01) were significant
      predictors of adequate bowel preparation. Adequate bowel preparation was
      associated with a significant increase in caecal intubation rates (OR 5.3, P =
      0.001). CONCLUSIONS: A shorter (<8 h) interval between end of bowel preparation
      and start of colonoscopy yielded better bowel cleansing than a longer (>8 h)
      interval. Adequate bowel preparation led to improved caecal intubation rates.

PMID- 22998354
TI  - Nanoemulsions containing octyl methoxycinnamate and solid particles of TiO2:
      preparation, characterization and in vitro evaluation of the solar protection
      factor.
AB  - The objective of this work was to develop and evaluate the physical-chemical
      properties of oil-in-water nanoemulsions for application as nanocosmetics for sun
      protection. Oil-in-water dispersions were processed by ultrasound (US) to obtain
      small emulsion droplets. These emulsions were obtained in the presence of
      commercial nonionic surfactants based on polyoxides and avocado oil as the oil
      phase. The US generated small but unstable droplets. This problem was solved by
      using a different surfactant, with a longer ethylene oxide chain, able to promote
      stabilization by steric mechanisms. The light scattering technique was used to
      characterize the nanoemulsions by their dispersed droplets' size, size
      distribution and variation of distribution with time (stability). Chemical and
      physical sunscreens - octyl methoxycinnamate (OMC) and titanium dioxide (TiO2),
      respectively - were added to the stable system. The anti-UVB activity of the
      nanoemulsions and their components were evaluated by the method of Mansur et al.
      (1986) and spectral transmittance. The solar protection factor (SPF) was
      proportional to the OMC and TiO2 concentrations. The in vitro OMC release was
      evaluated, and the presence of TiO2 in the nanoemulsion did not affect the
      release profile, which showed the diffusion-dependent kinetics of the active
      ingredient in the formulation.

PMID- 22998353
TI  - Genetic load is associated with hypothalamic-pituitary-adrenal axis dysregulation
      in macaques.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis pathway is
      associated with several neuropsychiatric disorders, including post-traumatic
      stress disorder (PTSD), major depressive disorder (MDD), schizophrenia and
      alcohol abuse. Studies have demonstrated an association between HPA axis
      dysfunction and gene variants within the cortisol, serotonin and opioid signaling
      pathways. We characterized polymorphisms in genes linked to these three
      neurotransmitter pathways and tested their potential interactions with HPA axis
      activity, as measured by dexamethasone (DEX) suppression response. We determined
      the percent DEX suppression of adrenocorticotropic hormone (ACTH) and cortisol in
      62 unrelated, male rhesus macaques. While DEX suppression of cortisol was robust
      amongst 87% of the subjects, ACTH suppression levels were broadly distributed
      from -21% to 66%. Thirty-seven monkeys from the high and low ends of the ACTH
      suppression distribution (18 'high' and 19 'low' animals) were genotyped at
      selected polymorphisms in five unlinked genes (rhCRH, rhTPH2, rhMAOA, rhSLC6A4
      and rhOPRM). Associations were identified between three variants (rhCRH-2610C>T,
      rhTPH2 2051A>C and rh5-HTTLPR) and level of DEX suppression of ACTH. In addition,
      a significant additive effect of the 'risk' genotypes from these three loci was
      detected, with an increasing number of 'risk' genotypes associated with a blunted
      ACTH response (P = 0.0009). These findings suggest that assessment of multiple
      risk alleles in serotonin and cortisol signaling pathway genes may better predict
      risk for HPA axis dysregulation and associated psychiatric disorders than the
      evaluation of single gene variants alone. 

PMID- 22998355
TI  - Sustained low clinical event rates in real-world patients receiving everolimus
      eluting coronary stent system from a large, prospective, condition of approval
      study: 2-year clinical outcomes from the XIENCE V USA Study.
AB  - OBJECTIVES: This 2-year follow-up of the XIENCE V USA study examines both the
      long-term safety and effectiveness of the everolimus-eluting coronary stent
      system (EECSS) in real-world patients. BACKGROUND: The safety and effectiveness
      of EECSS at 1 year in real-world clinical settings have been demonstrated in
      XIENCE V USA trial with low rates of target lesion revascularization (TLR),
      cardiac death, myocardial infarction (MI), and stent thrombosis (ST). Data on
      whether efficacy is maintained after 1 year and the event rate of very late stent
      thrombosis (VLST) between 1 and 2 years have not yet been reported. METHODS:
      XIENCE V USA is a prospective, multicenter, single-arm, FDA required condition of
      approval study designed to examine the safety and effectiveness of EECSS in an
      all-inclusive, consecutively enrolled population from real-world clinical
      settings. Clinical end-point events, including ST, cardiac death, MI, and
      revascularization were adjudicated by an independent Clinical Events Committee.
      RESULTS:  Four thousand eight hundred and seventy-three (96.4%) out of 5,054
      participants (1,875 standard-risk; 3,059 extended-risk) reached 2-year follow-up.
      The 2-year rate of Academic Research Consortium (ARC)-defined definite and
      probable ST was 0.96% (95% CI 0.70-1.28) in the overall population and 0.34% (95%
      CI 0.12-0.74) and 1.33% (95% CI 0.95-1.81) in the standard-risk and extended-risk
      cohorts, respectively. The rate of VLST was 0.06% in the overall population, 0.0%
      in the standard-risk, and 0.10% in the extended-risk cohorts. The 2-year
      composite rate of cardiac death and ARC-defined MI was 8.9% (95% CI 8.08-9.70) in
      the overall population and 5.6% (95% CI 4.61-6.78) and 10.8% (95% CI 9.71-11.94)
      in the standard-risk and extended-risk cohorts, respectively. CONCLUSION: Low
      event rates observed at 1 year were maintained through 2 years. Despite the
      increased number of patients who discontinued dual antiplatelet therapy by 2
      years, the ST rate remained consistently low, and <1% at 2 years due to low VLST
      occurrence. These results demonstrate continued safety and effectiveness of the
      XIENCE V everolimus-eluting stent in a highly complex, real-world patient
      population through 2 years.

PMID- 22998356
TI  - Outcomes of general anesthesia for noncardiac surgery in a series of patients
      with Fontan palliation.
AB  - OBJECTIVES: To describe the experience of a single, tertiary care institution in
      the care of patients with Fontan physiology undergoing anesthesia for noncardiac
      surgery. BACKGROUND: The Fontan procedure was developed in 1971 to palliate
      patients with univentricular cardiac physiology leading to long-term survival of
      these patients, who may now present as adults for noncardiac surgery. METHODS: We
      retrospectively reviewed the medical records of Fontan patients 16 years and
      older who underwent general anesthesia for noncardiac surgery at Mayo Clinic in
      Rochester, Minnesota. Preoperative data, perioperative course, intraoperative and
      postoperative hemodynamic, pulmonary, cardiovascular, and renal complications
      were described. RESULTS: Thirty-nine general anesthetics were administered to 31
      patients for noncardiac surgery after Fontan palliation. Perioperative
      complications occurred in 12 of the 39 (31%) noncardiac surgeries, and there was
      one postoperative death that occurred on day 13 after ventral hernia repair. The
      two patients who had complications that did not resolve (long-term dialysis and
      death) had ejection fractions well below the mean for the group (22% and 28%).
      CONCLUSION: It may be more appropriate for Fontan patients to undergo anesthesia
      for noncardiac surgery in a tertiary institution, particularly patients with an
      ejection fraction of <30%. Intraoperative arterial blood pressure monitoring and
      overnight admission are likely appropriate for most cases.

PMID- 22998357
TI  - Skin ultrasound examination proves useful in diagnosing two cases of solid cystic
      hidradenoma.

PMID- 22998358
TI  - Serum testosterone and depressive symptoms in severe OSA patients.
AB  - Obstructive sleep apnoea (OSA), also characterised by hypoxia-related sleep-
      fragmentation, has been studied in relation to depression and serum testosterone
      deficit. In middle-aged men, it has been reported the association between
      depressive mood and low serum testosterone level; however, no data are available
      about this association in OSA patients. Therefore, the aim of this study was to
      investigate in adult obese males, affected by severe OSA, the relationship
      between serum testosterone concentration and depressive symptoms, in order to
      identify among all measured parameters (serum testosterone morning concentration,
      polysomnography parameters, body mass index, Epworth Sleepiness Scale) those
      predictors for OSA-related depression. Forty patients diagnosed with severe OSA
      and forty subjects for the control-matched group were enroled in the study. The
      results indicated that the serum testosterone in OSA group was significantly
      lower than in controls. In addition, the OSA group presented a level of
      depression although moderate, yet significantly higher than controls.
      Furthermore, a statistically significant inverse correlation has been found
      between serum testosterone level and depressive symptoms. Among all variables,
      serum testosterone level was shown to be the only independent variable
      significantly predictor for depression in OSA patients. 

PMID- 22998359
TI  - Theoretical design of a fluorene-based light-driven molecular rotary motor with
      constant rotation.
AB  - A fluorene-based light-driven molecular rotary motor with constant rotation has
      been designed by means of ab initio molecular orbital calculations. A model
      molecule is obtained by a chemical modification of 9-(5-methyl-2-phenyl-2
      cyclopenten-1-ylidene)-9H-fluorene (MPCPF) which we  reported recently. Despite
      that MPCPF has a great advantage that the thermal helical inversion proceeds with
      a much lower energy barrier than those in previous model molecules, a small
      energy difference between the M- and the P-helical isomers is possible to cause a
      fast equilibration between them after  electronic relaxation around the conical
      intersection (CIX), and therefore, a backward rotation from the M-helical isomer
      is not always suppressed effectively. In order to overcome this defect of MPCPF,
      we modified MPCPF by a bridge of a pentamethylene chain between the 2 position of
      the phenyl group and the psesudoaxial position of the C(5) atom in the 2
      cyclopenten-1-ylidene ring. The modified molecule with a pentamethylene bridge
      (denoted by M5-PCPF) energetically destabilizes a conformation in the M-helical
      region and so passes through the M-helical region without any trap in the full
      rotary process, which leads to direct conversion from a stable P-helical isomer
      to another stable P-helical isomer via CIX. Therefore, M5-PCPF is expected to be
      a light-driven molecular rotary motor with constant rotation speed as well as
      unidirectionality.

PMID- 22998360
TI  - The sexual dimorphism of the sacro-iliac joint: an investigation using geometric
      morphometric techniques.
AB  - The ability to correctly estimate the sex of skeletal remains is vital in
      forensic sciences. This article investigates the sexual dimorphism of the human
      sacro-iliac joint, using geometric morphometric techniques that assess
      morphological characters better than the traditional approaches for recording
      outline shapes, which are subject to quantification and inter-observer problems.
      Eight two-dimensional landmarks were recorded from digital images of 29 female
      and 35 male auricular surfaces of the ilium and sacrum. The specimens were
      analyzed using geometric morphometric methods (Generalized Procrustes analysis,
      relative warp analysis, Goodall's F) and multivariate statistics (ANOVA, MANCOVA,
      principal component analysis, discriminant function analysis [DFA]). Both the
      size and shape of the analyzed structures were found to be sexually dimorphic.
      The DFA illustrated that when the form of both the iliac and sacral articular
      surface is taken as a predictor variable, 94.5% of the individuals are assigned
      to the correct sex. The successful sex determination obtained by the DFA makes
      the further study of the sacro-iliac joint's sexual dimorphism promising.

PMID- 22998361
TI  - Expression of the Chlamydomonas reinhardtii sedoheptulose-1,7-bisphosphatase in
      Dunaliella bardawil leads to enhanced photosynthesis and increased glycerol
      production.
AB  - Bioengineering of photoautotrophic microalgae into CO(2) scrubbers and producers
      of value-added metabolites is an appealing approach in low-carbon economy. A
      strategy for microalgal bioengineering is to enhance the photosynthetic carbon
      assimilation through genetically modifying the photosynthetic pathways. The
      halotolerant microalgae Dunaliella possess a unique osmoregulatory mechanism,
      which accumulates intracellular glycerol in response to extracellular
      hyperosmotic stresses. In our study, the Calvin cycle enzyme sedoheptulose 1,7
      bisphosphatase from Chlamydomonas reinhardtii (CrSBPase) was transformed into
      Dunaliella bardawil, and the transformant CrSBP showed improved photosynthetic
      performance along with increased total organic carbon content and the osmoticum
      glycerol production. The results demonstrate that the potential of photosynthetic
      microalgae as CO(2) removers could be enhanced through modifying the
      photosynthetic carbon reduction cycle, with glycerol as the carbon sink.

PMID- 22998362
TI  - Female genital mutilation/cutting (FGM/C): survey of RANZCOG fellows, diplomates
      & trainees and FGM/C prevention and education program workers in Australia and
      New Zealand.
AB  - BACKGROUND: Female genital mutilation/cutting (FGM/C) is traditionally practised
      in parts of Africa, the Middle East and South-East Asia. Migration has brought
      FGM/C to the attention of health practitioners in industrialised nations. It is
      not known whether FGM/C procedures are being performed in Australia and New
      Zealand, where legislation has been passed banning the practice. AIMS: To survey
      RANZCOG Fellows, Trainees and Diplomates, and FGM/C education and prevention
      program workers, about their experience with women and children affected by
      FGM/C, specifically to identify whether FGM/C is being performed in Australia or
      New Zealand. METHODS: Electronic survey distributed via e-mail to RANZCOG
      Fellows, Trainees and Diplomates and FGM/C program workers in Australia and New
      Zealand between November 2010 and February 2011. RESULTS: 530 responses were
      received from RANZCOG Fellows, Trainees and Diplomates, with an overall response
      rate of 18.5%. Thirty-four responses were received from FGM/C program workers.
      Five RANZCOG respondents and two FGM/C program workers cited anecdotal evidence
      that FGM/C is being performed in Australia and New Zealand. 21.2% (82) of RANZCOG
      respondents had been asked to re-suture following delivery, and 11 respondents
      had done so at least once. Two RANZCOG respondents had been asked to perform
      FGM/C on a baby, girl or young woman. CONCLUSIONS: There is no conclusive
      evidence of FGM/C being performed in Australia and New Zealand, either from
      direct reports or children presenting with complications, although re-suturing
      post-delivery is occurring. Anecdotal evidence suggests that it is most likely
      that people other than registered health practitioners are performing FGM/C.

PMID- 22998363
TI  - Stepwise intensification of insulin therapy in type 2 diabetes management-
      exploring the concept of the basal-plus approach in clinical practice.
AB  - Basal insulin provides an effective method for initiating insulin therapy in
      people with Type 2 diabetes, resulting in significant improvements in glycaemic
      control, lower rates of hypoglycaemia and less weight gain than either prandial
      or premixed insulin regimens. However, the progressive nature of Type 2 diabetes
      and the inability of basal insulin to correct excessive postprandial glucose
      excursions mean that insulin therapy will eventually need to be intensified,
      typically by adding prandial insulin as part of a basal-bolus or premixed insulin
      regimen. The aim of this review is to summarize recent clinical evidence for a
      staged 'basal-plus' strategy for insulin intensification where one, two or three
      prandial insulin injections are added to basal insulin according to individual
      need. In the early stages of insulin therapy, most individuals seem to achieve
      favourable glycaemic control with basal insulin alone, or in combination with a
      single prandial insulin injection. The addition of a single prandial insulin
      injection at the largest meal is well tolerated and associated with significant
      improvements in glycated haemoglobin (HbA(1c)), low rates of hypoglycaemia and
      limited weight gain. More people achieve recommended HbA(1c) targets with a basal
      plus strategy, compared with twice-daily premixed insulin therapy, with lower
      rates of hypoglycaemia. The data indicate that a step-by-step approach with the
      basal-plus strategy is a promising alternative method of insulin intensification
      that allows for individualization of treatment and may delay progression to a
      full basal-bolus insulin replacement therapy for many individuals.

PMID- 22998364
TI  - Reply to comment on: oral health status during pregnancy: rural-urban comparisons
      of oral disease burden among antenatal women in Sri Lanka.

PMID- 22998365
TI  - Learning and cognitive deficits in hypoxic neonatal rats intensified by BAX
      mediated apoptosis: protective role of glucose, oxygen, and epinephrine.
AB  - Hypoxic brain injury during neonatal development can lead to neuronal damage and
      produce learning and cognitive impairments. TOPRO-3 staining was used to
      visualize cell loss and real-time polymerase chain reaction (PCR) analysis of BAX
      mRNA was used to evaluate the level of apoptosis in the cerebral cortex,
      cerebellum, brain stem, and striatum of hypoxic neonatal rats and hypoxic rats
      resuscitated with glucose, oxygen, and epinephrine. The long-term effects of
      neonatal hypoxic insult on cognition and behavior were studied using Morris water
      maze experiment on 1-month-old rats exposed to neonatal hypoxia. In hypoxic
      neonatal rats, a significant cell loss (p < .001) within the brain regions was
      observed in TOPRO-3 staining and BAX mRNA expression was significantly
      upregulated (p < .001). Immediate resuscitation of hypoxic neonates with glucose,
      alone and along with oxygen, significantly downregulated (p < .001) BAX mRNA
      expression. The BAX expression in epinephrine resuscitated and 100% oxygen
      resuscitated groups were found to be upregulated in the brain regions. In water
      maze experiment, 1-month-old rats exposed to neonatal hypoxia spent lesser time
      in the platform quadrant (p < .001) and showed longer escape latency (p < .001)
      highlighting the learning and cognitive deficits. Our study revealed the effect
      of glucose resuscitation alone and along with oxygenation in ameliorating the
      spatial memory and learning deficits induced by neonatal hypoxic insult mediated
      brain cell loss.

PMID- 22998367
TI  - Ruthenium-catalyzed aldehyde functionality reshuffle: selective synthesis of E-2
      arylcinnamaldehydes from E-beta-bromostyrenes and aryl aldehydes.
AB  - A new concept for highly selective synthesis of E-2-arylcinnamaldehydes has been
      developed via a formal arylformylation of E-beta-bromostyrenes with readily
      available aryl aldehydes. This strategy involves an overall reshuffle of the
      aldehyde functionality with a loss of hydrogen bromide.

PMID- 22998366
TI  - Enhanced solubilization and desorption of organochlorine pesticides (OCPs) from
      soil by oil-swollen micelles formed with a nonionic surfactant.
AB  - The effect of oil-swollen micelles formed with nonionic surfactant
      polyoxyethylene sorbitan monooleate (Tween 80), cosurfactant 1-pentanol, and
      linseed oil on the solubilization and desorption of organochlorine pesticides
      (OCPs) including DDT and gamma-HCH from both loam soil and clay soil were
      investigated. Results showed that the solubilizing capacities of oil-swollen
      micelles were dependent on the critical micelle concentration (CMC) of Tween 80.
      Once the concentrations of oil-swollen micelles exceeded the CMC of Tween 80, the
      oil-swollen micelles exhibited much higher solubilizing capacity than empty Tween
      80 micelles for the two OCPs. Desorption tests revealed that oil-swollen micelles
      could successfully enhance desorption of OCPs from both loam soil and clay soil.
      However, compared with the efficiencies achieved by empty Tween 80 micelles, oil
      swollen micelles exhibited their superiority to desorb OCPs only in loam soil
      water system while was less effective in clay soil-water system. Distribution of
      Tween 80, 1-pentanol and linseed oil in soil-water system revealed that the
      difference in the sorption behavior of linseed oil onto the two soils is
      responsible for the different effects of oil-swollen micelles on the desorption
      of OCPs in loam soil and clay soil systems. Therefore, oil-swollen micelles
      formed with nonionic surfactant Tween 80 are better candidates over empty micelle
      counterparts to desorb OCPs from soil with relatively lower sorption capacity for
      oil fraction, which may consequently enhance the availability of OCPs in soil
      environment during remediation processes of contaminated soil.

PMID- 22998368
TI  - The pharmacokinetics and pharmacodynamics of  valsartan  in the post-myocardial
      infarction population.
AB  - INTRODUCTION: The most common risk factors for heart failure are hypertension and
      myocardial infarction. Angiotensin receptor blockers (ARBs) attenuate the
      deleterious effects of angiotensin II. Valsartan is a once or twice daily ARB
      that is FDA-approved for hypertension, LV dysfunction post-myocardial infarction
      and congestive heart failure as both an adjunct in ACE-inhibitor tolerant, and
      alternative in ACE-I intolerant patients. AREAS COVERED: This article presents a
      comprehensive review of the literature regarding the pharmacokinetics and
      pharmacodynamics of valsartan, with particular attention paid to the post
      myocardial infarction population. EXPERT OPINION: Valsartan is a safe, well
      tolerated and readily titratable ARB. In addition to its vasodilatory effects
      there are pleotropic effects associated with the ARB such as modulation of a
      number of neurohormonal regulators, cytokines and small molecules. Given the
      clear evidence-based benefits above and beyond its hypertensive properties, it
      has the potential, if priced appropriately, to grow in its impact as a
      pharmacotherapeutic long after its patent expires.

PMID- 22998369
TI  - Trifluoromethylation of alpha-haloketones.
AB  - The C-X bond (X = Br, Cl) of alpha-haloketones is smoothly trifluoromethylated
      with the fluoroform-derived CuCF(3) reagent recently developed in our
      laboratories. This is the first nucleophilic alpha-trifluoromethylation reaction
      of carbonyl compounds and a rare example of CF(3)-C(sp(3)) coupling. The
      transformation employs only low-cost chemicals and cleanly occurs in up to 99%
      yield at room temperature, thereby providing an unprecedentedly easy entry to
      valuable 2,2,2-trifluoroethylketones.

PMID- 22998370
TI  - Neonatal transfer of membrane-bound stem cell factor improves survival and heart
      function in aged mice after myocardial ischemia.
AB  - Stem cell mobilization to injured tissue contributes to neovascularization,
      resulting in regeneration after myocardial infarction (MI). We previously showed
      that direct cardiac injection of a recombinant lentivirus (LV) that engineers
      expression of membrane-bound stem cell factor (mSCF) improves outcomes
      immediately after MI. In this study, we evaluated the effect of neonatal LV/mSCF
      transduction on MI outcomes in aged mice. We constructed a recombinant LV
      harboring an alpha-myosin heavy chain promoter that drives mSCF expression and
      injected it into the temporal vein of neonatal mice. One year later, sustained
      expression of mSCF in the adult mouse hearts was detected by genomic and
      quantitative RT-PCR and immunohistochemistry. To evaluate the contribution of
      neonatal LV/mSCF delivery to recovery from MI, we induced an MI in adult LV/mSCF
      transduced, LV only-transduced, and nontransduced control mice. Strikingly,
      LV/mSCF transduction reduced infarct scar size, enhanced angiogenesis, improved
      ventricular function, and significantly increased survival of the mice. Regional
      overexpression of CD11b, a marker of monocytes and proangiogenic cells, was
      observed on monocytes isolated from the infarcted hearts of LV/mSCF-transduced
      mice. Our data suggest a model of neonatal gene delivery that leads to sustained
      mSCF expression during adulthood to aid recovery from MI and prevent heart
      failure.

PMID- 22998371
TI  - Temperature influence on the structure and interfacial properties of surfactin
      micelle: a molecular dynamics simulation study.
AB  - Surfactin is an efficient biosurfactant excreted by different strains of Bacillus
      subtilis. Our study provides a molecular view of the temperature dependence of
      the structure and the interfacial properties of un-ionized surfactin micelles.
      The overall size and shape, the surface area, the radial density distribution of
      the micelles, the conformation of the hydrocarbon chain, and the
      intramolecular/intermolecular hydrogen bonds formed in surfactin molecules were
      investigated. The micelles were mostly in sphere shapes, and the radii of
      surfactin micelle were estimated to be around 2.2 nm. The peptide rings occupied
      most of the surface of the micelles. Small amounts of beta-turn and gamma-turn
      structures were found in the conformations of the peptide rings. When the
      temperature increased, the shape of the peptide rings became planar; the solvent
      accessible surface area decreased as temperature dehydration occurred. At 343 K
      some hydrocarbon chains reversed their orientation (flip-flopped). In addition,
      the stability of the hydrogen bond interactions in the micelles decreases with
      the increasing temperature.

PMID- 22998372
TI  - Response to comment from Dr. Sloan: 'look what's going down'.

PMID- 22998373
TI  - The effect of parental intellectual disability status on child protection service
      worker decision making.
AB  - BACKGROUND: There is evidence to suggest that parents with an intellectual
      disability (ID) constitute a higher proportion of child-protective services (CPS)
      cases than would be expected based on the prevalence of ID in the general
      population. Researchers have suggested that the stereotypic assumptions and
      expectations that CPS workers have about parents with an ID might influence
      decisions and responses made to such parents. This study examined whether
      parental ID (having an ID vs. not) had an effect on CPS workers' emotional
      reactions, attributions and decisions about risk to the child, whether to remove
      the child and workers' general willingness to help the parent. METHOD: Two
      hundred and twelve CPS workers read vignettes describing parents who were
      labelled as either having or not having an ID. Workers responded to the vignettes
      by making ratings of their emotional reactions, attributions and decisions
      regarding risk, removal and helping. RESULTS: CPS workers made significantly
      higher ratings of pity, willingness to help and risk for parents with an ID than
      for parents without an ID. Lower ratings of anger and disgust were found for
      parents with an ID than for parents without an ID. Parents' intellectual status
      did not have a direct effect on workers' attributions or removal decisions.
      CONCLUSIONS: The results show evidence for the influence of stereotypes regarding
      parental ID due to its differential effect on CPS workers' emotional reactions
      and decisions about child risk and their willingness to help.

PMID- 22998374
TI  - Risks of emerging infectious diseases: evolving threats in a changing area, the
      mediterranean basin.
AB  - The Mediterranean basin is a biodiversity hotspot; it has historically had a
      large human presence that has shaped ecosystems for millennia. As the cradle of
      many civilizations, the area was one of the main theatres for transitions that
      punctuated both human and pathogen histories, which are intimately linked. Today
      we are living through another great historical transition summarized in the
      expression 'global changes'. In this context, we are witnessing a rise in the
      emergence of pathogens widely associated with aforementioned global changes. The
      Mediterranean basin might be especially vulnerable to this phenomenon due to the
      acute consequences global changes will have in this key intercontinental
      interface region. In addition, Arab revolutions and European economic crisis are
      creating both sanitary issues and presenting new opportunities to improve
      infectious disease control and prevention in the region. The aim of this review
      is to identify the impacts that ongoing changes might have on the risk of
      infectious disease emergence in the Mediterranean basin. We focussed on three key
      domains undergoing transformations: (i) resources, namely safe drinking water and
      animal products, (ii) socio-economic factors including health inequalities within
      countries and poor sanitary conditions linked to ongoing conflicts and (iii)
      movements of people and goods that are reshaped by current changes and are
      intimately linked to the risk of disease proliferation. Building on recent
      examples, we try to identify upcoming challenges and discuss ways to meet them in
      the light of existing international human and veterinary health guidelines and
      their possible improvements. 

PMID- 22998375
TI  - Expression analyses of the genes harbored by the type 2 diabetes and pediatric
      BMI associated locus on 10q23.
AB  - BACKGROUND: There is evidence that one of the key type 2 diabetes (T2D) loci
      identified by GWAS exerts its influence early on in life through its impact on
      pediatric BMI. This locus on 10q23 harbors three genes, encoding
      hematopoietically expressed homeobox (HHEX), insulin-degrading enzyme (IDE) and
      kinesin family member 11 (KIF11), respectively. METHODS: We analyzed the impact
      of adipogeneis on the mRNA and protein expression levels of these genes in the
      human adipocyte Simpson-Golabi-Behmel syndrome (SGBS) cell line in order to
      investigate which could be the culprit gene(s) in this region of linkage
      disequilibrium. RESULTS: Following activation of differentiation with a PPARgamma
      ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of
      80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte
      states. We also observed decreases in KIF11 and IDE protein levels, but
      conversely we observed a dramatic increase in HHEX protein levels. Subsequent
      time course experiments revealed some marked changes in expression as early as
      three hours after activation of differentiation. CONCLUSION: Our data suggest
      that the expression of all three genes at this locus are impacted during SGBS
      adipogenesis and provides insights in to the possible mechanisms of how the genes
      at this 10q23 locus could influence both adipocyte differentiation and
      susceptibility to T2D through insulin resistance.

PMID- 22998376
TI  - Characterization of the distal esophagus high-pressure zone with manometry,
      ultrasound and micro-computed tomography.
AB  - BACKGROUND: We sought to determine how the individual components of the distal
      esophagus and proximal stomach form the gastroesophageal junction high-pressure
      zone (GEJHPZ) antireflux barrier. METHODS: An endoscopic ultrasound/manometry
      catheter was pulled through the proximal stomach and distal esophagus in 20
      normal subjects. The axial length and width of individual structures on
      endoscopic ultrasound were measured. The anatomic orientation of gastroesophageal
      junction (GEJ) components was examined in two organ donor specimens using micro
      computed tomography (micro-CT). KEY RESULTS: The three distinct structures
      identified within the GEJHPZ, from distal to proximal, were as follows: the
      gastric clasp and sling muscle fiber complex, crural diaphragm, and lower
      esophageal circular smooth muscle fibers (LEC). The LEC was statistically
      significantly thicker than adjacent esophageal muscles. These structures were
      associated with three pressure peaks. The pressure peak produced by the
      clasp/sling fiber complex often overlapped with the pressure peak from the crural
      diaphragm. The most proximal peak, associated with the LEC, was significantly
      greater and bimodal in nine of 20 subjects. This bimodal LEC pressure peak
      correlated with two areas of thickened muscle observed with ultrasound. Micro-CT
      of GEJ from organ donors confirmed the two areas of thickened muscle. CONCLUSIONS
      & INFERENCES: Three distinct anatomic structures, the clasp and sling muscle
      fibers, crural diaphragm, and LEC combine to form the antireflux barrier of the
      proximal stomach and distal esophagus. The clasp and sling muscle fibers combine
      with the crural diaphragm to form a distal pressure profile. The more proximal
      LEC has a bimodal pressure profile in some patients.

PMID- 22998378
TI  - Pituitary insufficiency: a cause of hypoglycemia in an elderly diabetic patient.

PMID- 22998377
TI  - Gastrointestinal hemorrhage and antithrombotic drug use in geriatric patients.

PMID- 22998379
TI  - Clinical utility of accelerometry in geriatric rehabilitation.

PMID- 22998380
TI  - J-curve association between economic status and diabetes independent of
      functional disability in Japanese elderly.

PMID- 22998381
TI  - Case of acute cerebellitis as a result of varicella zoster virus infection
      without skin manifestations.

PMID- 22998382
TI  - Case of beriberi showing improved cerebral blood flow after thiamine treatment.

PMID- 22998383
TI  - A healthy, 81-year-old woman with toxoplasmic encephalitis.

PMID- 22998384
TI  - High risk of adverse drug reactions in elderly patients taking six or more drugs:
      analysis of inpatient database.

PMID- 22998385
TI  - C-kit-positive acute myelogenous leukemia effectively treated with imatinib: a
      case report and review of the literature.

PMID- 22998386
TI  - A double-blind randomized  placebo-controlled study on the  clinical and
      microbial effects of an essential oil mouth rinse used by patients in supportive
      periodontal care.
AB  - AIM: This 3-month double-blind randomized placebo-controlled study evaluated the
      clinical and microbial effects of an essential oil mouth rinse used as an adjunct
      to mechanical plaque control by patients in supportive periodontal care. MATERIAL
      AND METHODS: Fifty patients were randomly allocated to an essential oil group
      (Listerine((r))  Coolmint; Johnson & Johnson, New Brunswick, NJ, USA) or placebo
      group to rinse twice per day as an adjunct to mechanical plaque control. At
      baseline and after 3 months, plaque index (PI), gingivitis index (GI), probing
      pocket depth, bleeding on probing (BoP) and clinical attachment level were
      registered. Subgingival plaque samples were collected for the detection and
      quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis, Tannerella forsythia, Treponema denticola, Micromonas micros,
      Prevotella intermedia, Fusobacterium genus and Streptococcus mutans by means of
      real-time PCR (qPCR). Patient's compliance, satisfaction and side effects were
      registered. RESULTS: Twenty-three patients in the essential oil group (mean age:
      57) and 21 in the placebo group (mean age: 55) with acceptable oral hygiene at
      intake (mean PI <1.5 on a scale of 5) adhered to the study protocol. Gingivitis
      index, PI and BoP significantly reduced over time (P <= 0.029); however, between
      group analyses revealed no significant differences. There was no significant
      change over time neither in detection frequency nor load for any of the
      microbiota. Daily rinsing with an essential oil rinse was found safe and
      perceived beneficial by the patients. CONCLUSION: Patients in supportive
      periodontal care who are fairly compliant with oral hygiene may not benefit from
      additional mouth rinsing using an essential oil solution.

PMID- 22998388
TI  - Fucosyl neoglycoprotein binds to mouse epididymal spermatozoa and inhibits sperm
      binding to the egg zona pellucida.
AB  - Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals,
      and this sugar coding plays an important role in cell-to-cell recognition
      processes. In this study, our aims were to determine the distribution of sperm
      receptors with activity for fucosyl- and galactosyl glycans and to address
      whether monosugar neoglycoproteins functionally mimic the binding between zona
      pellucida (ZP) glycoproteins and spermatozoa. In mouse epididymal spermatozoa
      with intact acrosomes, fucopyranosyl bovine serum albumin (BSA-Fuc) bound to the
      segment of the acrosome, the equatorial segment, and the postacrosome region of
      the sperm head. Galactosyl BSA (BSA-Gal) binding activity was similar to that of
      BSA-Fuc, but was weaker. In acrosome-reacted spermatozoa treated with the Ca(2+)
      ionophore A23187, BSA-zuc binding was lost in the apical segment of the acrosome
      but remained in the equatorial segment and postacrosome regions. BSA-Gal binding
      to the equatorial region was increased. In the presence of 2.5 MUg ml(-1) BSA
      Fuc, in vitro sperm-ZP binding was significantly decreased, indicating that
      fucosyl BSA functionally mimics ZP glycoproteins during sperm-egg ZP
      interactions. At the same concentration, BSA-Gal was not effective. Fucosyl BSA
      that efficiently inhibited the sperm-ZP binding can mimic the ZP glycoconjugate
      and has potential for use as a sperm fertility control agent in mouse. 

PMID- 22998387
TI  - Induced pluripotency and oncogenic transformation are related processes.
AB  - Induced pluripotent stem cells (iPSCs) have the potential for creating patient
      specific regenerative medicine therapies, but the links between pluripotency and
      tumorigenicity raise important safety concerns. More specifically, the methods
      employed for the production of iPSCs and oncogenic foci (OF), a form of in vitro
      produced tumor cells, are surprisingly similar, raising potential concerns about
      iPSCs. To test the hypotheses that iPSCs and OF are related cell types and, more
      broadly, that the induction of pluripotency and tumorigenicity are related
      processes, we produced iPSCs and OF in parallel from common parental fibroblasts.
      When we compared the transcriptomes of these iPSCs and OF to their parental
      fibroblasts, similar transcriptional changes were observed in both iPSCs and OF.
      A significant number of genes repressed during the iPSC formation were also
      repressed in OF, including a large cohort of differentiation-associated genes.
      iPSCs and OF shared a limited number of genes that were upregulated relative to
      parental fibroblasts, but gene ontology analysis pointed toward monosaccharide
      metabolism as upregulated in both iPSCs and OF. iPSCs and OF were distinct in
      that only iPSCs activated a host of pluripotency-related genes, while OF
      activated cellular damage and specific metabolic pathways. We reprogrammed
      oncogenic foci (ROF) to produce iPSC-like cells, a process dependent on Nanog.
      However, the ROF had reduced differentiation potential compared to iPSC,
      suggesting that oncogenic transformation leads to cellular changes that impair
      complete reprogramming. Taken together, these findings support a model in which
      OF and iPSCs are related, yet distinct cell types, and in which induced
      pluripotency and induced tumorigenesis are similar processes.

PMID- 22998389
TI  - Inhibition and induction of glutathione S-transferases by flavonoids: possible
      pharmacological and toxicological consequences.
AB  - Many studies reviewed herein demonstrated the potency of some flavonoids to
      modulate the activity and/or expression of glutathione S-transferases (GSTs).
      Because GSTs play a crucial role in the detoxification of xenobiotics, their
      inhibition or induction may significantly affect metabolism and biological
      effects of many drugs, industrials, and environmental contaminants. The effect of
      flavonoids on GSTs strongly depends on flavonoid structure, concentration, period
      of administration, as well as on GST isoform and origin. Moreover, the results
      obtained in vitro are often contrary to the vivo results. Based on these facts,
      the revelation of important flavonoid-drug or flavonoid-pollutant interaction has
      been complicated. However, it should be borne in mind that ingestion of certain
      flavonoids in combination with drugs or pollutants (e.g., acetaminophen,
      simvastatin, cyclophosphamide, cisplatine, polycyclic aromatic hydrocarbons,
      chlorpyrifos, acrylamide, and isocyanates), which are GST substrates, could have
      significant pharmacological and toxicological consequences. Although reasonable
      consumptions of a flavonoids-rich diet (that may lead to GST induction) are
      mostly beneficial, the uncontrolled intake of high concentrations of certain
      flavonoids (e.g., quercetin and catechins) in dietary supplements (that may cause
      GST inhibition) may threaten human health.

PMID- 22998391
TI  - The philosopher in the clinic.

PMID- 22998390
TI  - Combining fetal sonography with genetic and allele pathogenicity studies to
      secure a neonatal diagnosis of Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome (BBS) is a rare pediatric ciliopathy characterized by
      marked clinical variability and extensive genetic heterogeneity. Typical
      diagnosis of BBS is secured at a median of 9 years of age, and sometimes well
      into adolescence. Here, we report a patient in whom prenatal detection of
      increased nuchal fold, enlarged echogenic kidneys, and polydactyly prompted us to
      screen the most commonly mutated genes in BBS and the phenotypically and
      genetically overlapping ciliopathy, Meckel-Gruber syndrome (MKS). We identified
      the common Met390Arg mutation in BBS1 in compound heterozygosity with a novel
      intronic variant of unknown significance (VUS). Testing of mRNA harvested from
      primary foreskin fibroblasts obtained shortly after birth revealed the VUS to
      induce a cryptic splice site, which in turn led to a premature termination and
      mRNA degradation. To our knowledge, this is the earliest diagnosis of BBS in the
      absence of other affected individuals in the family, and exemplifies how
      combining clinical assessment with genetic and timely assays of variant
      pathogenicity can inform clinical diagnosis and assist with patient management in
      the prenatal and neonatal setting.

PMID- 22998392
TI  - Resonance metallic stents do not effectively relieve extrinsic ureteral
      compression in pediatric patients.
AB  - BACKGROUND AND PURPOSE: Use of metallic stents (Resonance) has been reported in
      the literature to be effective in relieving extrinsic obstruction in adults.
      Successful patency rates have been reported to be around 83.3%. The use of
      Resonance stents in children has not been reported. We present our experience
      with these stents in addressing extrinsic ureteral obstruction in the pediatric
      population. PATIENTS AND METHODS: We identified two patients who underwent
      placement of Resonance stents for extrinsic compression at the Children's
      Hospital of the University of Pittsburgh Medical Center. The first patient is a
      12-year-old girl with a solitary left kidney who had a diagnosis of pelvic
      rhabdomyosarcoma; she was treated with surgery followed by adjuvant
      chemoradiation. Two years post-treatment, worsening renal function secondary to
      ureteral strictures developed. The second patient is a 14-year-old girl with a
      history of Gardner syndrome. Recurrent desmoid tumors developed in her pelvis and
      retroperitoneum that led to right ureteral obstruction, necessitating a
      nephrostomy tube. RESULTS: Both patients underwent successful technical placement
      of a Resonance stent. The time to failure for patient 1 was 3 months and for
      patient 2, 3 weeks. The first patient presented to the emergency department 3
      months poststent in renal failure with a creatinine level of 13.7 mg/dL. This
      necessitated nephrostomy tube placement and hemodialysis. Ultimately, she needed
      an ileal ureter to preserve renal function. She is off hemodialysis and has a
      creatinine level of 2.2 mg/dL.The second patient, recurrent episodes of
      pyelonephritis, worsening hydronephrosis, and flank pain developed with just the
      Resonance stent in place. It was elected to remove the Resonance stent and
      replace the nephrostomy tube. She needed extensive ureterolysis, a right subtotal
      ureterectomy with a right to left ureteroureterostomy. CONCLUSION: We did not
      find the use of these stents to be effective in children. The time to failure was
      significantly shorter in children than those reported in the literature for
      adults.

PMID- 22998393
TI  - Clinical and preclinical validation of the serum free light chain assay:
      identification of the critical difference for optimized clinical use.
AB  - OBJECTIVES: The use of the assay for the measurements of free light chains in
      serum (sFLCs) is increasing. However, there are technical limitations that
      potentially affect the use in serial measurements. We need further knowledge on
      the standards of analytical precision, the utility of conventional population
      based reference values and the critical difference (CD) between serial results
      required for significance. To answer these questions, the biological variation
      must be known. METHODS: We determined the biological variation in healthy
      individuals and patients with plasma cell dyscrasia (PCD). We assessed the
      imprecision of the analysis in use from FreeLiteTM. We determined the reference
      interval (RI) in 170 healthy individuals. RESULTS: The biological variation is
      identical for healthy individuals and patients with PCD. The imprecision of the
      sFLC analysis cannot fulfil the desirable performance standards for a laboratory
      test, but are within the manufacturer's +/-20% variation for quality control
      samples. RI showed a significant increase for kappa FLC and kappa/lambda ratio
      with age, but not for lambda. Critical difference was calculated to be 24% and
      23% for kappa and lambda, respectively. CONCLUSIONS: We suggest the use of an age
      dependent RI. When monitoring patients with PCD, their own former results are the
      best reference, and knowledge on CD is a valuable tool, which we describe for the
      first time. Also, it challenges the recently proposed International Myeloma
      Working Group 'paraprotein relapse criteria', recommending an increase of more
      than 25% in the involved FLC to indicate the need for initiation of retreatment.
      We recommend revision of this criterion.

PMID- 22998394
TI  - Inpatient electronic prescribing data can be used to identify 'lost' discharge
      codes for diabetes.
AB  - AIM: Accurate assessment of missed discharge codes for diabetes is critical for
      effective planning of hospital diabetes services. We wished to estimate the
      frequency of missed discharge diagnostic codes for diabetes and the impact missed
      codes would have on diabetes-related payments to the hospital. METHODS: We linked
      Patient Administration System data to the Prescribing Information and
      Communication System. We defined diabetes as those having a discharge code for
      diabetes in the Patient Administration System and those on anti-diabetic
      medication in the Prescribing Information and Communication System. Based on the
      two sources, we calculated the estimated missed discharge codes for diabetes
      using the capture-recapture technique. We generated the Healthcare Resource Group
      for a given admission before and after correction for the missed code to estimate
      the impact that correction would make on payments to the hospital. RESULTS: Among
      the 171 067 admissions linked, 22 412 (13.1%) had a code for diabetes at
      discharge. An additional 2706 admissions were classified as having diabetes based
      on prescription data. The capture-recapture technique estimated there were 4588
      (2.7% of all admissions) admissions with diabetes missed by current coding, of
      which 2706 (60%) would be obtained from prescription data. After adding a
      diabetes diagnostic code, 12.8% of the missed admissions with diabetes resulted
      in a change to the Healthcare Resource Group tariff code and payment. CONCLUSION:
      The use of electronic prescription data is a simple solution to correct for
      missed discharge diagnostic codes.

PMID- 22998395
TI  - 'It looks like you just want them when things get rough': civil society
      perspectives on negative trial results and stakeholder engagement in HIV
      prevention trials.
AB  - Civil society organizations (CSOs) have significantly impacted on the politics of
      health research and the field of bioethics. In the global HIV epidemic, CSOs have
      served a pivotal stakeholder role. The dire need for development of new
      prevention technologies has raised critical challenges for the ethical engagement
      of community stakeholders in HIV research. This study explored the perspectives
      of CSO representatives involved in HIV prevention trials (HPTs) on the impact of
      premature trial closures on stakeholder engagement. Fourteen respondents from
      South African and international CSOs representing activist and advocacy groups,
      community mobilisation initiatives, and human and legal rights groups were
      purposively sampled based on involvement in HPTs. Interviews were conducted from
      February-May 2010. Descriptive analysis was undertaken across interviews and key
      themes were developed inductively. CSO representatives largely described positive
      outcomes of recent microbicide and HIV vaccine trial terminations, particularly
      in South Africa, which they attributed to improvements in stakeholder engagement.
      Ongoing challenges to community engagement included the need for principled
      justifications for selective stakeholder engagement at strategic time-points, as
      well as the need for legitimate alternatives to CABs as mechanisms for
      engagement. Key issues for CSOs in relation to research were also raised. 

PMID- 22998396
TI  - ReaxFF molecular dynamics simulations of oxidation of toluene at high
      temperatures.
AB  - Aromatic hydrocarbon fuels, such as toluene, are important components in real jet
      fuels. In this work, reactive molecular dynamics (MD) simulations employing the
      ReaxFF reactive force field have been performed to study the high-temperature
      oxidation mechanisms of toluene at different temperatures and densities with
      equivalence ratios ranging from 0.5 to 2.0. From the ReaxFF MD simulations, we
      have found that the initiation consumption of toluene is mainly through three
      ways, (1) the hydrogen abstraction reactions by oxygen molecules or other small
      radicals to form the benzyl radical, (2) the cleavage of the C-H bond to form
      benzyl and hydrogen radicals, and (3) the cleavage of the C-C bond to form phenyl
      and methyl radicals. These basic reaction mechanisms are in good agreement with
      available chemical kinetic models. The temperatures and densities have composite
      effects on toluene oxidation; concerning the effect of the equivalence ratio, the
      oxidation reaction rate is found to decrease with the increasing of equivalence
      ratio. The analysis of the initiation reaction of toluene shows that the hydrogen
      abstraction reaction dominates the initial reaction stage at low equivalence
      ratio (0.5-1.0), while the contribution from the pyrolysis reaction increases
      significantly as the equivalence ratio increases to 2.0. The apparent activation
      energies, E(a), for combustion of toluene extracted from ReaxFF MD simulations
      are consistent with experimental results.

PMID- 22998397
TI  - Assessing patients with myocardial infarction and nonobstructed coronary arteries
      (MINOCA).

PMID- 22998398
TI  - Frequency, cost and impact of inter-island referrals in the Solomon Islands.
AB  - INTRODUCTION: Providing quality health services to people living in remote areas
      is central to global efforts to achieve universal access to health care.
      Effective referral systems are especially critical in resource-limited countries
      where small populations are separated by considerable distances, geographic
      challenges and the limitations of human resources for health. This study aimed to
      build an evidence base on inter-island referrals in the Solomon Islands, in
      particular regarding the number of referrals, reasons for referrals, and cost, to
      ultimately provide recommendations regarding referral practice effectiveness and
      efficiency. METHODS: Data were taken from the referral database collected and
      maintained by the National Referral Hospital (NRH) in the capital, Honiara. Data
      included age, sex, ward or department visited, date of travel back to home port,
      home port and province. Data were available and included for 2008, 6 months of
      2009, all of 2010 and 1 month of 2011; a total of 31 months. Travel costs were
      taken from NRH administrative information and included in the analysis. In
      addition, 10 qualitative interviews were conducted with clinicians and policy
      makers in the tertiary hospital and one provincial hospital to gather information
      regarding inter-island referrals, their appropriateness and challenges faced.
      RESULTS: In the Solomon Islands, referrals from outer islands to the NRH are
      substantial and are gradually increasing over time. The two most populous
      provinces outside of the capital, Western and Malaita, represented 51% of all
      referrals in the study period. Of those referred, 21% were less than 15 years of
      age - even though 40% of the country's population is under 15 - with 30% being
      young adults of 15-24 years. Orthopaedic conditions comprised the largest number
      of referrals, with obstetric and gynaecological conditions a close second. The
      cost of referrals is rapidly increasing and was almost US$350,000 per year for
      the NRH alone. The amount budgeted for patient travel from the provinces to the
      NRH was a fraction of what is needed to cover the current number of referrals
      leading to a substantial budget shortfall. There did not appear to be a clear
      link between number of doctors in each province and the rate of referrals.
      CONCLUSION: Improving the appropriateness of referrals can have a substantial
      impact on access, quality of care and costs. Improvements in equipment in remote
      facilities, in human resources for health and in information technology can
      strengthen the quality of care in outer islands. Reducing the burden on referral
      facilities will allow them to provide appropriate care to those most in need
      while building public trust in all layers of the health system.

PMID- 22998399
TI  - Geriatric urolithiasis in the emergency department: risk factors for
      hospitalisation and emergency management patterns of acute urolithiasis.
AB  - BACKGROUND: Urolithiasis is one of the most common conditions seen in emergency
      departments (ED) worldwide, with an increasing frequency in geriatric patients
      (>65 years). Given the high costs of emergency medical urolithiasis treatment,
      the need to optimise management is obvious. We aimed to determine risk factors
      for hospitalisation and evaluate diagnostic and emergency treatment patterns by
      ED physicians in geriatric urolithiasis patients to assist in optimising
      treatment. METHODS: After receiving ethics committee approval, we examined the
      records of emergency urolithiasis admissions to our ED between January 2000 and
      December 2010 to determine risk factors for hospitalisation and to evaluate
      current diagnostic and emergency treatment patterns in geriatric urolithiasis
      patients. RESULTS: 1,267 consecutive patients at least 20 years of age with
      confirmed urolithiasis (1,361 ED visits) and complete follow-up data were
      analyzed. Geriatric patients comprised 10% of urolithiasis patients with more
      than half of them experiencing their first urolithiasis episode at ED admission.
      Although stone site, side and size did not significantly differ between groups,
      urinary stone disease was more severe in the elderly. The risk of severe
      complications correlated with increasing age, female sex and diabetes mellitus.
      Geriatric patients had a two-fold greater likelihood of being hospitalised. A
      significantly lower percentage of geriatric patients received combined analgesic
      therapy for pain management (37% vs. 64%, p = <0.001) and supportive expulsive
      treatment (9% vs. 24%, p = <0.001). CONCLUSION: Geriatric patients with
      urolithiasis have a higher morbidity than younger patients and may be
      undertreated concerning analgetic and expulsive treatment in ED.

PMID- 22998400
TI  - Isolated limb infusion with hyperthermia and chemotherapy for advanced limb
      malignancy: factors influencing toxicity.
AB  - BACKGROUND: The isolated limb infusion (ILI) technique is a simpler and less
      invasive alternative to isolated limb perfusion, which allows regional
      administration of high-dose chemotherapy to patients with advanced melanoma and
      other malignancies restricted to a limb. METHODS: Patients from two institutions,
      treated by ILI between 1998 and 2009 for extensive disease restricted to a limb,
      were included. The cohort included 31 patients with melanoma who presented with
      in-transit metastases or an extensive primary lesion, one patient with squamous
      cell carcinoma and another with epithelioid sarcoma not suitable for local
      surgical treatment. RESULTS: A complete response was achieved in 26.3% of
      patients and a partial response in 52.6%. Toxicity was assessed according to the
      Wieberdink limb toxicity scale. Grade II toxicity was noted in 39.5% of patients,
      grade III in 50% and grade IV in 10.5%. Toxicity was correlated with the results
      of a number of clinical and laboratory tests. The toxicity of melphalan and
      actinomycin D was dose-dependent. For melphalan, the relationship between
      toxicity and mean dose was as follows: grade II--34.7 mg; grades III and IV--47.5
      mg (P = 0.012). The relationship between toxicity and maximum serum creatine
      phosphokinase (CPK) was as follows: grade II--431.5 U/L; grades III and IV--3228
      U/L (P = 0.010). CONCLUSION: Toxicity after ILI is dose-dependent and serum CPK
      correlates with toxicity.

PMID- 22998401
TI  - E-waste recycling: where does it go from here?
AB  - E-waste recycling has become a hotly debated global issue. This study, using
      China as a case study, analyzes the environmental, economic, and social
      implications of e-waste recycling in the developing world. More practical
      approaches, taking into account local economic and social conditions and the
      principles of Extended Producer Responsibility, are recommended to alleviate the
      increasing environmental disruption from improper e-waste disposal.

PMID- 22998402
TI  - Changes in the Oswestry Disability Index that predict improvement after lumbar
      fusion.
AB  - OBJECT: Clinical studies use both disease-specific and generic health outcomes
      measures. Disease-specific measures focus on health domains most relevant to the
      clinical population, while generic measures assess overall health-related quality
      of life. There is little information about which domains of the Oswestry
      Disability Index (ODI) are most important in determining improvement in overall
      health-related quality of life, as measured by the 36-Item Short Form Health
      Survey (SF-36), after lumbar spinal fusion. The objective of the study is to
      determine which clinical elements assessed by the ODI most influence improvement
      of overall health-related quality of life. METHODS: A single tertiary spine
      center database was used to identify patients undergoing lumbar fusion for
      standard degenerative indications. Patients with complete preoperative and 2-year
      outcomes measures were included. Pearson correlation was used to assess the
      relationship between improvement in each item of the ODI with improvement in the
      SF-36 physical component summary (PCS) score, as well as achievement of the SF-36
      PCS minimum clinically important difference (MCID). Multivariate regression
      modeling was used to examine which items of the ODI best predicted achievement
      for the SF-36 PCS MCID. The effect size and standardized response mean were
      calculated for each of the items of the ODI. RESULTS: A total of 1104 patients
      met inclusion criteria (674 female and 430 male patients). The mean age at
      surgery was 57 years. All items of the ODI showed significant correlations with
      the change in SF-36 PCS score and achievement of MCID for the SF-36 PCS, but only
      pain intensity, walking, and social life had r values > 0.4 reflecting moderate
      correlation. These 3 variables were also the dimensions that were independent
      predictors of the SF-36 PCS, and they were the only dimensions that had effect
      sizes and standardized response means that were moderate to large. CONCLUSIONS:
      Of the health dimensions measured by the ODI, pain intensity, walking, and social
      life best predicted improvement in overall health-related quality of life, as
      measured using the SF-36 PCS.

PMID- 22998403
TI  - Minimally invasive resection of lumbar synovial cysts from a contralateral
      approach.
AB  - Synovial cysts of the lumbar spine result from degeneration of the facet capsule
      and often mimic symptoms commonly seen with herniated intervertebral discs. In
      symptomatic patients, the prevalence of synovial cysts may be as high as 10%.
      Although conservative management is possible, the majority of patients will
      require resection. Traditional procedures for lumbar synovial cyst resection use
      an ipsilateral approach requiring partial or complete resection of the
      ipsilateral facet complex, possibly leading to further destabilization. A
      contralateral technique using minimally invasive tubular retractors for synovial
      cyst resection avoids facet disruption. The authors report 2 cases of a minimally
      invasive synovial cyst resection via a contralateral laminotomy. In both cases,
      complete resection of the cyst was achieved while sparing the facet joint.

PMID- 22998404
TI  - Outcomes of instrumented fusion in the pediatric cervical spine.
AB  - OBJECT: The most common cause of cervical spine arthrodesis in the pediatric
      population is instability related to congenital or traumatic pathology.
      Instrumenting the cervical spine can be challenging given smaller anatomical
      structures, less ossified bone, and future growth potential and development.
      Studies in adult patients have suggested that using screw constructs results in
      improved outcomes with lower rates of instrumentation failure. However, the
      pediatric literature is limited to small retrospective series. Based on a review
      of the literature and their own patient series, the authors report that
      instrumenting the pediatric cervical spine with screw constructs may be safer and
      more effective than using wiring techniques. METHODS: The authors reviewed the
      existing pediatric cervical spine arthrodesis literature and contributed 31 of
      their own cases from September 1, 2007, to January 1, 2011. They reviewed 204
      abstracts from January 1, 1966, to December 31, 2010, and 80 manuscripts with 883
      total patients were included in the review. They recorded demographic,
      radiographic, and outcomes data-as well as surgical details-with a focus on
      fusion rates and complications. Patients were then grouped into categories based
      upon the procedure performed: 1) patients who underwent fusions bridging the
      occipitocervical junction and 2) patients who underwent fusion of the cervical
      spine that did not include the occiput, thus including atlantoaxial and subaxial
      fusions. Patients were further subdivided according to the type of
      instrumentation used-some had posterior cervical fusion with wiring (with or
      without rod implantation); others had posterior cervical fusion with screws.
      RESULTS: The entire series comprised 914 patients with a mean age of 8.30 years.
      Congenital abnormalities were encountered most often (in 55% of cases), and
      patients had a mean follow-up of 32.5 months. From the entire cohort, 242
      patients (26%) experienced postsurgical complications, and 50 patients (5%) had
      multiple complications. The overall fusion rate was 94.4%. For occipitocervical
      fusions (N = 285), both screw and wiring groups had very high fusion rates (99%
      and 95%, respectively, p = 0.08). However, wiring was associated with a higher
      complication rate. From a sample of 252 patients, 14% of those treated with screw
      instrumentation had complications, compared with 50% of patients treated with
      wiring (p < 0.05). In cervical fusions not involving the occipitocervical
      junction (N = 181), screw constructs had a 99% fusion rate, whereas wire
      instrumentation only had an 83% fusion rate (p < 0.05). Similarly, patients who
      underwent screw fixation had a lower complication profile (15%) when compared
      with those treated with wiring constructs (54%, p < 0.05). CONCLUSIONS: The
      results of this study are limited by variations in construct design, use of
      orthoses, follow-up duration, and newer adjuvant products promoting fusions.
      However, a literature review and the authors' own series of pediatric cases
      suggest that instrumentation of the cervical spine in children may be safer and
      more efficacious using screw constructs rather than wiring techniques.

PMID- 22998405
TI  - Solute's perspective on how trimethylamine oxide, urea, and guanidine
      hydrochloride affect water's hydrogen bonding ability.
AB  - While the thermodynamic effects of trimethylamine oxide (TMAO), urea, and
      guanidine hydrochloride (GdnHCl) on protein stability are well understood, the
      underlying mechanisms of action are less well characterized and, in some cases,
      even under debate. Herein, we employ the stretching vibration of two infrared
      (IR) reporters, i.e., nitrile (C=N) and carbonyl (C?O), to directly probe how
      these cosolvents mediate the ability of water to form hydrogen bonds with the
      solute of interest, e.g., a peptide. Our results show that these three agents,
      despite having different effects on protein stability, all act to decrease the
      strength of the hydrogen bonds formed between water and the infrared probe. While
      the behavior of TMAO appears to be consistent with its protein-protecting
      ability, those of urea and GdnHCl are inconsistent with their role as protein
      denaturants. The latter is of particular interest as it provides strong evidence
      indicating that although urea and GdnHCl can perturb the hydrogen-bonding
      property of water their protein-denaturing ability does not arise from a simple
      indirect mechanism.

PMID- 22998406
TI  - Nestin-expressing cells in the gut give rise to enteric neurons and glial cells.
AB  - BACKGROUND: Neuronal stem cells (NSCs) are promising for neurointestinal disease
      therapy. Although NSCs have been isolated from intestinal musclularis, their
      presence in mucosa has not been well described. Mucosa-derived NSCs are
      accessible endoscopically and could be used autologously. Brain-derived Nestin
      positive NSCs are important in endogenous repair and plasticity. The aim was to
      isolate and characterize mucosa-derived NSCs, determine their relationship to
      Nestin-expressing cells and to demonstrate their capacity to produce neuroglial
      networks in vitro and in vivo. METHODS: Neurospheres were generated from
      periventricular brain, colonic muscularis (Musc), and mucosa-submucosa (MSM) of
      mice expressing green fluorescent protein (GFP) controlled by the Nestin promoter
      (Nestin-GFP). Neuronal stem cells were also grown as adherent colonies from
      intestinal mucosal organoids. Their differentiation potential was assessed using
      immunohistochemistry using glial and neuronal markers. Brain and gut-derived
      neurospheres were transplanted into explants of chick embryonic aneural hindgut
      to determine their fate. KEY RESULTS: Musc- and MSM-derived neurospheres
      expressed Nestin and gave rise to cells of neuronal, glial, and mesenchymal
      lineage. Although Nestin expression in tissue was mostly limited to glia co
      labelled with glial fibrillary acid protein (GFAP), neurosphere-derived neurons
      and glia both expressed Nestin in vitro, suggesting that Nestin+/GFAP+ glial
      cells may give rise to new neurons. Moreover, following transplantation into
      aneural colon, brain- and gut-derived NSCs were able to differentiate into
      neurons. CONCLUSIONS & INFERENCES: Nestin-expressing intestinal NSCs cells give
      rise to neurospheres, differentiate into neuronal, glial, and mesenchymal
      lineages in vitro, generate neurons in vivo and can be isolated from mucosa.
      Further studies are needed for exploring their potential for treating
      neuropathies.

PMID- 22998408
TI  - Experimental study of electromagnetic heating of gold nanoparticle dispersions at
      200 kHz.
AB  - AIM: Remote heating of gold nanoparticles (GNPs) by low frequency electromagnetic
      field has been recently proposed as a potential thermal treatment for deep-seated
      tumors - almost all the studies were conducted on a commercial device at 13.56
      MHz. This work investigates the electromagnetic heating of GNP dispersions at 200
      kHz. METHODS: GNPs are synthesized based on an improved citrate reduction method,
      and the influence of particle concentration and impurity on the bulk heating
      effect at 200 kHz are investigated. RESULTS & CONCLUSION: The results demonstrate
      that GNPs alone can contribute to an appreciable bulk temperature increase, which
      increases with GNP concentration in a nonlinear fashion. For a nonmagnetic
      material, the specific absorption rate of GNPs can reach that of Fe(3)O(4)
      nanoparticle dispersions. Such a result cannot be explained by either the Joule
      heating or hysteresis heating mechanism.

PMID- 22998407
TI  - Assembly and properties of heterobimetallic Co(II/III)/Ca(II) complexes with aquo
      and hydroxo ligands.
AB  - The use of water as a reagent in redox-driven reactions is advantageous because
      it is abundant and environmentally compatible. The conversion of water to
      dioxygen in photosynthesis illustrates one example, in which a redox-inactive
      Ca(II) ion and four manganese ions are required for function. In this report we
      describe the stepwise formation of two new heterobimetallic complexes containing
      Co(II/III) and Ca(II) ions and either hydroxo or aquo ligands. The preparation of
      a four-coordinate Co(II) synthon was achieved with the tripodal ligand, N,N',N"
      [2,2',2"-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido,
      [MST](3-). Water binds to [Co(II)MST](-) to form the five-coordinate
      [Co(II)MST(OH(2))](-) complex that was used to prepare the Co(II)/Ca(II) complex
      [Co(II)MST(MU-OH(2))Ca(II)?15-crown-5(OH(2))](+) ([Co(II)(MU
      OH(2))Ca(II)OH(2)](+)). [Co(II)(MU-OH(2))CaOH(2)](+) contained two aquo ligands,
      one bonded to the Ca(II) ion and one bridging between the two metal ions, and
      thus represents an unusual example of a heterobimetallic complex containing two
      aquo ligands spanning different metal ions. Both aquo ligands formed
      intramolecular hydrogen bonds with the [MST](3-) ligand. [Co(II)MST(OH(2))](-)
      was oxidized to form [Co(III)MST(OH(2))] that was further converted to
      [Co(III)MST(MU-OH)Ca(II)?15-crown-5](+) ([Co(III)(MU-OH)Ca(II)](+)) in the
      presence of base and Ca(II)OTf(2)/15-crown-5. [Co(III)(MU-OH)Ca(II)](+) was also
      synthesized from the oxidation of [Co(II)MST](-) with iodosylbenzene (PhIO) in
      the presence of Ca(II)OTf(2)/15-crown-5. Allowing [Co(III)(MU-OH)Ca(II)](+) to
      react with diphenylhydrazine afforded [Co(II)(MU-OH(2))Ca(II)OH(2)](+) and
      azobenzene. Additionally, the characterization of [Co(III)(MU-OH)Ca(II)](+)
      provides another formulation for the previously reported Co(IV)-oxo complex,
      [(TMG(3)tren)Co(IV)(MU-O)Sc(III)(OTf)(3)](2+) to one that instead could contain a
      Co(III)-OH unit.

PMID- 22998409
TI  - Carrier status of leptospirosis among cattle in Sri Lanka: a zoonotic threat to
      public health.
AB  - Leptospirosis is a zoonotic disease of global importance and one of the
      notifiable diseases in Sri Lanka. Recent studies on human leptospirosis have
      suggested that the cattle could be one of the important reservoirs for human
      infection in the country. However, there is a dearth of local information on
      bovine leptospirosis, including its implications for human transmission. Thus,
      this study attempted to determine the carrier status of pathogenic Leptospira spp
      in cattle in Sri Lanka. A total of 164 cattle kidney samples were collected from
      the meat inspection hall in Colombo city during routine inspection procedures
      conducted by the municipal veterinary surgeons. The DNA was extracted and
      subjected to nested PCR for the detection of leptospiral flaB gene. Amplicons
      were sequenced, and phylogenic distances were calculated. Of 164 samples, 20
      (12.2%) were positive for flaB-PCR. Sequenced amplicons revealed that Leptospira
      species were deduced to L. borgpetersenii (10/20, 50%), L. kirschneri (7/20, 35%)
      and L. interrogans (3/20, 15%). The results indicate that a high proportion of
      the sampled cattle harbour a variety of pathogenic Leptospira spp, which can
      serve as important reservoirs for human disease. 

PMID- 22998410
TI  - A biomechanical model of anther opening reveals the roles of dehydration and
      secondary thickening.
AB  - Understanding the processes that underlie pollen release is a prime target for
      controlling fertility to enable selective breeding and the efficient production
      of hybrid crops. Pollen release requires anther opening, which involves changes
      in the biomechanical properties of the anther wall. In this research, we develop
      and use a mathematical model to understand how these biomechanical processes lead
      to anther opening. Our mathematical model describing the biomechanics of anther
      opening incorporates the bilayer structure of the mature anther wall, which
      comprises the outer epidermal cell layer, whose turgor pressure is related to its
      hydration, and the endothecial layer, whose walls contain helical secondary
      thickening, which resists stretching and bending. The model describes how
      epidermal dehydration, in association with the thickened endothecial layer,
      creates forces within the anther wall causing it to bend outwards, resulting in
      anther opening and pollen release. The model demonstrates that epidermal
      dehydration can drive anther opening, and suggests why endothecial secondary
      thickening is essential for this process (explaining the phenotypes presented in
      the myb26 and nst1nst2 mutants). The research hypothesizes and demonstrates a
      biomechanical mechanism for anther opening, which appears to be conserved in many
      other biological situations where tissue movement occurs.

PMID- 22998411
TI  - A review of applications of tea tree oil in dermatology.
AB  - Tea tree oil (TTO) is an essential oil, steam-distilled from the Australian
      native plant, Melaleuca alternifolia. It has a minimum content of terpinen-4-ol
      and a maximum content of 1, 8-cineole. Terpinen-4-ol is a major TTO component
      which exhibits strong antimicrobial and anti-inflammatory properties. Tea tree
      oil exerts antioxidant activity and has been reported to have broad-spectrum
      antimicrobial activity against bacterial, viral, fungal, and protozoal infections
      affecting skin and mucosa. Several studies have suggested the uses of TTO for the
      treatment of acne vulgaris, seborrheic dermatitis, and chronic gingivitis. It
      also accelerates the wound healing process and exhibits anti-skin cancer
      activity. This review opens up new horizons for dermatologists in the use of this
      herbal agent. 

PMID- 22998412
TI  - The effects of age on temporal fine structure sensitivity in monaural and
      binaural conditions.
AB  - OBJECTIVE: To extend the study of Hopkins and Moore (2011) by examining the
      effect of age in the medium age range on sensitivity to temporal fine structure
      (TFS), which is assumed to be represented in the patterns of phase locking in the
      auditory nerve. DESIGN: Monaural TFS sensitivity was assessed using the TFS1 test
      (Moore & Sek, 2009) at centre frequencies of 850 and 2000 Hz, and binaural TFS
      sensitivity was assessed using the TFS-LF test (Hopkins & Moore, 2010a) at centre
      frequencies of 500 and 850 Hz, using a sensation level of 30 dB. STUDY SAMPLE:
      Thirty-five newly recruited normal-hearing subjects (thresholds better than 20 dB
      HL from 250 to 6000 Hz) were tested. Their ages ranged from 22 to 61 years.
      RESULTS: There was a significant correlation between age and TFS sensitivity at
      all frequencies for both TFS tests. For the single centre frequency (850 Hz) that
      was used for both tests, scores for the two tests were modestly but significantly
      correlated. CONCLUSIONS: Sensitivity to TFS decreases with increasing age. The
      monaural and binaural TFS tests appear to reflect at least somewhat distinct
      auditory processes.

PMID- 22998413
TI  - Measurements of earplug attenuation under supra-aural and circumaural headphones.
AB  - OBJECTIVE: Supra-aural audiometric headphones are generally not recommended for
      use in measuring the attenuation of earplugs, because contact between the
      headphone and pinna and/or earplug could alter the attenuation obtained, and
      because of concerns of non-comparability between modes of excitation from supra
      aural headphones and the sound-field procedure required by the standardized
      method. In this study, we compared measurements of earplug attenuation obtained
      under Telephonics TDH-50P supra-aural headphones with measurements obtained under
      circumaural headphones designed expressly for such testing. DESIGN: The
      attenuation of three types of earplugs (foam, premolded quadruple-flange, and
      custom-molded) was measured in a repeated-measures design. STUDY SAMPLE: The
      study sample comprised 42 normal-hearing adults (21 females, 21 males). RESULTS:
      With the foam earplugs, nearly all of the attenuation measurements under the
      supra-aural headphones fell within 10 dB of the measurements under the
      circumaural headphones. With the flange and custom earplugs, approximately 10% of
      individuals obtained spuriously high attenuation under the supra-aural
      headphones. CONCLUSIONS: We conclude that standard supra-aural audiometric
      headphones are suitable for measuring the attenuation provided by foam earplugs.
      However, supra-aural headphones should not be used to measure the attenuation of
      flange or custom-molded earplugs. The potential exists for substantial over
      estimation of attenuation, especially of custom plugs.

PMID- 22998414
TI  - Firefighter hearing health: an informatics approach to screening, measurement,
      and research.
AB  - OBJECTIVE: The purpose of this study was to evaluate the use of a standardized
      interface terminology, the Omaha System, with respect to noise-induced hearing
      loss (NIHL). DESIGN: A descriptive, correlational design was employed for this
      secondary analysis with the data from an ongoing hearing protection intervention
      study. STUDY SAMPLE: A total of 346 firefighters were included. RESULTS: First,
      an evidence-based standardized care plan (EB-SCP) for hearing screening was
      developed and validated by clinical experts. Second, occupational health records
      were used to compute Omaha System Knowledge, Behavior, and Status outcomes.
      Third, research data were mapped to Omaha System rating scales. For Knowledge,
      the mean score was close to 'adequate' (3.7). For Behavior, the mean score was
      close to 'rarely appropriate' (2.2). For Status, the mean score was close to
      'minimal sign/symptom' (4.4). Significant positive relationships were found
      between Knowledge and Behavior (Spearman's rho =.13, p =.01), and between
      Behavior and hearing Status (Spearman's rho =.12, p =.02). CONCLUSIONS: Findings
      support the validity of the new Knowledge, Behavior, and hearing Status.
      Informatics methods such as the standardized NIHL EB-SCP and outcome data sets
      will create opportunities for clinical decision support and data exchange across
      various health care settings, thus supporting population-based hearing health
      assessments and outcomes.

PMID- 22998415
TI  - Auditory discrimination: the relationship between psychophysical and
      electrophysiological measures.
AB  - OBJECTIVES: This study aimed to (1) investigate the relationship between the
      acoustic change complex (ACC) and perceptual measures of frequency and intensity
      discrimination, and gap detection; and (2) examine the effects of acoustic change
      on the amplitudes and latencies of the ACC. DESIGN: Psychophysical thresholds for
      frequency and intensity discrimination and gap detection, as well as ACCs
      elicited by stimuli containing increments in frequency, or intensity or gaps,
      were recorded from the same group of subjects. The magnitude of the acoustic
      change was systematically varied for the ACC recording. STUDY SAMPLE: Twenty-six
      adults with normal hearing, ranging in age between 19 and 39 years. RESULTS:
      Electrophysiological and psychophysical measures for frequency and intensity
      discrimination were significantly correlated. Electrophysiological thresholds
      were comparable to psychophysical thresholds for intensity discrimination but
      were higher than psychophysical thresholds for gap detection and frequency
      discrimination. Increasing the magnitude of acoustic change increased the ACC
      amplitude but did not show consistent effects across acoustic dimensions for ACC
      latency. CONCLUSIONS: The ACC can be used as an objective index of auditory
      discrimination in frequency and intensity. The ACC amplitude is a better
      indicator for auditory processing than the ACC latency.

PMID- 22998416
TI  - Molecular interaction of poly(acrylic acid) gold nanoparticles with human
      fibrinogen.
AB  - The binding of fibrinogen to various nanoparticles can result in protein
      unfolding and exposure of cryptic epitopes that subsequently interact with cell
      surface receptors. This response is dependent on the size, charge, and
      concentration of the nanoparticle. Here we examine the binding kinetics of human
      fibrinogen to negatively charged poly(acrylic acid)-coated gold nanoparticles
      ranging in size from 7 to 22 nm. These particles have previously been shown to
      elicit an inflammatory response in human cells. The larger nanoparticles bound
      fibrinogen with increasing affinity and a slower dissociation rate. Each
      fibrinogen molecule could accommodate two 7 nm nanoparticles but only one when
      the diameter increased to 10 nm. Nanoparticles larger than 12 nm bound multiple
      fibrinogen molecules in a positively cooperative manner. However, in the presence
      of excess nanoparticle, fibrinogen induced aggregation of the larger particles
      that could bind more than one protein molecule. This is consistent with
      interparticle bridging by the fibrinogen. Taken together, these results
      demonstrate that subtle changes in nanoparticle size can influence protein
      binding both with the surface of the nanoparticle and within the protein corona.

PMID- 22998417
TI  - Dental neglect and adverse birth outcomes: a validation and observational study.
AB  - OBJECTIVES: The objectives of this study were to validate the Indian translation
      of the Dental Neglect Scale (DNS) among a sample of parturient Indian women and
      to investigate dental neglect as a possible risk indicator in adverse birth
      outcomes. SUBJECTS AND METHODS: Three hundred and sixteen parturient women were
      administered the DNS and the Modified Dental Beliefs Scale (MDBS) and were also
      clinically examined for oral health status. Information regarding socio-economic
      status, weeks of gestation and birth weight was also collected. A gestation
      period of less than 37 weeks was considered as preterm and a birth weight of less
      than 2500 gm as 'low birth weight'. RESULTS: The Indian version of the DNS was
      found to be reliable (Cronbach's Alpha = 0.72) and valid for assessing dental
      neglect among the women. Factor analysis of the DNS revealed a two-factor
      structure accounting for 56% variance. Dental neglect was higher among those with
      poorer oral health status, lower socio-economic and educational status.
      Multinomial logistic regression showed high dental neglect and negative dental
      beliefs and not poor oral health, as significant risk indicators for occurrence
      of adverse birth outcomes. CONCLUSION: The finding of an association of adverse
      birth outcomes with dental neglect and beliefs, but not with poor oral health
      could be due to the influence of other more important general factors which had a
      direct bearing on birth outcomes. There is a need for further research to assess
      the role of behavioural factors like dental neglect as risk indicators for
      adverse birth outcomes.

PMID- 22998418
TI  - Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on
      cadmium-induced testicular toxicity.
AB  - Cadmium (Cd) is a well-known testicular toxicant. This study was designed to
      explore the long-term effects of a single low dose of Cd on spermatogenesis, and
      testicular dysfunction and oxidative stress, and the therapeutic potential of
      date palm pollen extract (DPP) in averting such reproductive damage. Adult male
      Wistar rats received a single intraperitoneal injection of CdCl2 (0 or 1 mg kg(
      1) ). Twenty-four hours later, they started receiving DPP (0 or 40 mg kg(-1) )
      orally, once daily for 56 consecutive days. Cd exposure caused significant
      reproductive damage via reduced weight of the reproductive organs, which includes
      spermatological damage (decreased sperm count and motility and increased rates of
      sperm abnormalities), increased oxidative stress (increased malondialdehyde and
      decreased reduced glutathione levels), histological alterations (necrosis,
      inefficient to completely arrest spermatogenesis and a reduced Johnsen's score)
      and decreased serum testosterone level. DPP restored spermatogenesis and
      attenuated the toxic effects of Cd on the reproductive system to the levels
      observed in the control animals. These findings support the hypothesis that the
      testis is particularly sensitive to Cd, which can cause testicular damage and
      infertility. Treatment with DPP can ameliorate the deleterious effects of Cd,
      probably by activating testicular endocrine and antioxidant systems. 

PMID- 22998419
TI  - Conformational restriction approach to beta-secretase (BACE1) inhibitors: effect
      of a cyclopropane ring to induce an alternative binding mode.
AB  - Improvement of a drug's binding activity using the conformational restriction
      approach with sp3 hybridized carbon is becoming a key strategy in drug discovery.
      We applied this approach to BACE1 inhibitors and designed four stereoisomeric
      cyclopropane compounds in which the ethylene linker of a known amidine-type
      inhibitor 2 was replaced with chiral cyclopropane rings. The synthesis and
      biologic evaluation of these compounds revealed that the cis-(1S,2R) isomer 6
      exhibited the most potent BACE1 inhibitory activity among them. X-ray structure
      analysis of the complex of 6 and BACE1 revealed that its unique binding mode is
      due to the apparent CH-pi interaction between the rigid cyclopropane ring and the
      Tyr71 side chain. A derivatization study using 6 as a lead molecule led to the
      development of highly potent inhibitors in which the structure-activity
      relationship as well as the binding mode of the compounds clearly differ from
      those of known amidine-type inhibitors.

PMID- 22998420
TI  - Mepolizumab  treatment for asthma.
AB  - INTRODUCTION: Five percent of asthmatics have severe symptoms despite high doses
      of inhaled (ICS) or additional oral corticosteroids (OCS): these patients have
      high morbidity, risk for asthma death, and account for half of asthma healthcare
      spending. A subgroup (20 - 40%) of these has persistent airway eosinophilia and
      frequent exacerbations. Mepolizumab is a humanized monoclonal antibody that
      blocks binding of the key cytokine implicated specifically in eosinophil
      maturation and survival, interleukin-5, to its receptor. AREAS COVERED:
      Pharmacology, Phase I/IIa and Phase II/III studies of mepolizumab for asthma.
      Mepolizumab depleted blood and sputum eosinophils and partially reduced airway
      and bone marrow eosinophils. It also reduced airway remodeling. In unselected
      patients with moderate/severe asthma there was no clinically significant effect
      on lung function, but a trend to reduced exacerbation rates. When patients were
      selected for persistent sputum eosinophilia despite high-dose ICS/OCS, and
      frequent exacerbations, mepolizumab reduced exacerbations by 50%. EXPERT OPINION:
      Mepolizumab can reduce exacerbation rates in the severe asthma cohort who have
      eosinophilic airway inflammation despite corticosteroid treatment. This may be
      30% of severe asthmatics and represents a new and important treatment option.
      Further studies need to confirm efficacy and indications for asthma (and other
      eosinophilic airway disease), and to examine clinical consequences of reducing
      remodeling.

PMID- 22998421
TI  - Increasing dwell time of mitomycin C in the upper tract with a reverse
      thermosensitive polymer.
AB  - Abstract Background and Purpose: Topical chemotherapy for urothelial cancer is
      dependent on adequate contact time of the chemotherapeutic agent with the
      urothelium. To date, there has not been a reliable method of maintaining this
      contact for renal or ureteral urothelial carcinoma. We evaluated the safety and
      feasibility of using a reverse thermosensitive polymer to improve dwell times of
      mitomycin C (MMC) in the upper tract. MATERIALS AND METHODS: Using a porcine
      model, four animals were treated ureteroscopically with both upper urinary tracts
      receiving MMC mixed with iodinated contrast. One additional animal received MMC
      percutaneously. The treatment side had ureteral outflow blocked with a reverse
      thermosensitive polymer plug. MMC dwell time was monitored fluoroscopically and
      intrarenal pressures measured. Two animals were euthanized immediately, and three
      animals were euthanized 5 days afterward. RESULTS: In control kidneys, drainage
      occurred at a mean of 5.3+/-0.58 minutes. Intrarenal pressures stayed fairly
      stable: 9.7+/-14.0 cm H20. In treatment kidneys, dwell time was extended to 60
      minutes, when the polymer was washed out. Intrarenal pressures in the treatment
      kidneys peaked at 75.0+/-14.7 cm H20 and reached steady state at 60 cm H20.
      Pressures normalized after washout of the polymer with cool saline. Average
      washout time was 11.8+/-9.6 minutes. No histopathologic differences were seen
      between the control and treatment kidneys, or with immediate compared with
      delayed euthanasia. CONCLUSIONS: A reverse thermosensitive polymer can retain MMC
      in the upper urinary tract and appears to be safe from our examination of
      intrarenal pressures and histopathology. This technique may improve the efficacy
      of topical chemotherapy in the management of upper tract urothelial carcinoma.

PMID- 22998422
TI  - Caregiving of children with intellectual disabilities in China--an examination of
      affiliate stigma and the cultural thesis.
AB  - BACKGROUND: While caregivers of children with intellectual disabilities are
      burdened in every part of the world, it is suspected that particular contexts may
      make the situation worse. There is little literature on caregivers in China,
      where familial and clan responsibility rather than individual effort is
      emphasised, and where communal support, while treasured, is often lacking.
      METHOD: A total of 211 caregivers in two cities, one with and the other without
      randomised design, participated in a survey study that assessed affiliated
      stigma, loss of face, anxiety, mental health and empowerment. RESULTS: A
      proportion of 60.6% of participants were found to be conspicuous cases with
      mental disturbance of a level which required further professional attention.
      Participants with better resource appeared to have coped better, enjoying lower
      psychological distress, lower anxiety and a higher level of personal empowerment.
      Multiple regression analysis revealed that mental health is related to the
      affective dimension of affiliated stigma, loss of face and anxiety level. This
      was found to account for more than half the variance (55%). DISCUSSION: The
      subjective burden of care occurs not in isolation but in a cultural field.
      Chinese caregiving is characterised by a lack of formal support, and such
      cultural concerns as loss of face and strong affiliated stigma. This socio
      political context makes caregiving all the more challenging. The situation has to
      be addressed by both practitioners and policy makers if family caregiving is to
      be valued and made sustainable.

PMID- 22998423
TI  - First successful double-factor PGD for Lynch syndrome: monogenic analysis and
      comprehensive aneuploidy screening.
AB  - Preimplantation genetic diagnosis (PGD) has been applied worldwide for a great
      variety of single-gene disorders over the last 20 years. The aim of this work was
      to perform a double-factor preimplantation genetic diagnosis (DF-PGD) protocol in
      a family at risk for Lynch syndrome. The family underwent a DF-PGD approach in
      which two blastomeres from each cleavage-stage embryo were biopsied and used for
      monogenic and comprehensive cytogenetic analysis, respectively. Fourteen embryos
      were biopsied for the monogenic disease and after multiple displacement
      amplification (MDA), 12 embryos were diagnosed; 5 being non-affected and 7
      affected by the disease. Thirteen were biopsied to perform the aneuploidy
      screening by short-comparative genomic hybridization (CGH). The improved DF-PGD
      approach permitted the selection of not only healthy but also euploid embryos for
      transfer. This has been the first time a double analysis of embryos has been
      performed in a family affected by Lynch syndrome, resulting in the birth of two
      healthy children. The protocol described in this work offers a reliable
      alternative for single-gene disorder assessment together with a comprehensive
      aneuploidy screening of the embryos that may increase the chances of pregnancy
      and birth of transferred embryos.

PMID- 22998424
TI  - An International reference reagent for the detection of anti-human neutrophil
      antigen-1a.
AB  - BACKGROUND AND OBJECTIVES: Testing for neutrophil antibodies has become more
      common as awareness of transfusion-related acute lung injury (TRALI) has
      increased. However, unlike other areas of blood cell antibody testing, there are
      no certified reference reagents available with which laboratories can determine
      the sensitivity of detection of their assays. This report describes the
      production and evaluation of a freeze-dried preparation of human plasma, code
      09/284, containing anti-human neutrophil antigen-1a (anti-HNA-1a) for use as a
      minimum sensitivity reagent. MATERIALS AND METHODS: One-millilitre of aliquots of
      plasma containing anti-HNA-1a were freeze-dried in glass ampoules. To
      characterize the material, 24 laboratories took part in an international
      collaborative study. The participants evaluated doubling dilutions of the
      material using their in-house routine assays and recorded the highest dilution in
      which the antibody could be detected. RESULTS: When diluted 1 in 4, most
      laboratories were able to detect the anti-HNA-1a in the material, and the
      participants agreed that this was an appropriate level to set as the minimum
      sensitivity required. CONCLUSIONS: In October 2011, the WHO Expert Committee on
      Biological Standardization approved the material 09/284 as an International
      Reference Reagent for the detection of anti-HNA-1a.

PMID- 22998425
TI  - Impact of three years training on operations capacities of research ethics
      committees in Nigeria.
AB  - This paper describes a three-year project designed to build the capacity of
      members of research ethics committes to perform their roles and responsibilities
      efficiently and effectively. The project participants were made up of a cross
      section of the membership of 13 Research Ethics Committees (RECs) functioning in
      Nigeria. They received training to develop their capacity to evaluate research
      protocols, monitor trial implementation, provide constructive input to trial
      staff, and assess the trial's success in promoting community engagement in the
      research. Following the training, technical assistance was provided to
      participants on an ongoing basis and the project's impacts were assessed
      quantitatively and qualitatively. Results indicate that sustained investment in
      capacity building efforts (including training, ongoing technical assistance, and
      the provision of multiple tools) improved the participants' knowledge of both the
      ethical principles relevant to biomedical research and how effective REC should
      function. Such investment was also shown to have a positive impact on the
      knowledge levels of other RECs members (those who did not receive training) and
      the overall operations of the RECs to which the participants belonged. Building
      the capacity of REC members to fulfill their roles effectively requires sustained
      effort and investment and pays off by enabling RECs to fulfill their essential
      mission of ensuring that trials are conducted safely and ethically.

PMID- 22998426
TI  - The lived experiences of young people (13-16 years) with Type 1 diabetes mellitus
      and their parents--a qualitative phenomenological study.
AB  - AIMS: Within a programme of research aiming to develop a technology-based
      educational intervention for young people with Type 1 diabetes, this study aimed
      to explore adolescents' and parents' experiences of living with Type 1 diabetes
      from an interpretive phenomenological perspective. METHODS: In-depth interviews
      were conducted with 20 adolescents with Type 1 diabetes from a diabetes clinic in
      North West England, and 27 of their parents. RESULTS: Living with Type 1 diabetes
      in adolescence was characterized by three distinct stages: (1) adapting to the
      diagnosis; (2) learning to live with Type 1 diabetes; (3) becoming independent.
      Experiential learning was key to adolescents developing self-management skills
      and independence. Parents and health professionals were instrumental in
      facilitating environments that gave adolescents the freedom to learn through
      trial and error. They also provided the support, feedback and discussion
      necessary to facilitate such learning. CONCLUSIONS: For adolescents to become
      independent in Type 1 diabetes self-management, they must develop capability
      through experiential learning. It is important that parents and health
      professionals understand the important role they play in this process and have
      the skills to support adolescents in this way. Data from this study have been
      used to develop an online interactive 'Adolescent Diabetes Needs Assessment
      Tool', which assesses individual learning and support needs to aid the process of
      feedback and discussion.

PMID- 22998427
TI  - Differentiated expression of membrane type metalloproteinases (MMP-14, MMP-15)
      and pro-MMP2 in laryngeal squamous cell carcinoma. A novel mechanism.
AB  - Cancer progression involves multiple proteolytic interactions, with
      metalloproteinases (MMPs) performing a crucial role. MMP-2, a major MMP, plays a
      key role in the degradation of basement membranes. Mechanisms underlying MMP-2
      activation had to be investigated. Membrane-type matrix metalloproteinases are
      not only responsible for the regulation of extracellular matrix remodeling, but
      also involved in the activation of several inactive MMPs. The aim of this study
      was to evaluate the expression of pro-MMP2, MMP-14, and MMP-15 in tumor cells and
      tumor stroma. Immunohistochemical studies were performed on paraffin-embedded
      tissue sections including laryngeal squamous cell carcinoma (SCC). We found the
      expression of pro-MMP2 in 58% of cases, MMP-14 in 78%, and MMP-15 in 98% of cases
      of SCC. In all tumor cases, we revealed a higher expression of pro-MMP2 in tumor
      stoma than in tumor cells. The expression of MMP-14 and MMP-15 was higher in
      tumor cells than in the stroma. Moreover, we found a statistically significant
      difference between the expression of MMP-14 and MMP-15 in the tumor in comparison
      with the surrounding stroma (P < 0.05). An analysis of expression levels of MT
      MMPs by classification trees showed that the probability of metastases was
      related to decreased expression of MMP-14 and increased expression of MMP-15. Our
      results may suggest that tumor cells with low MMP-14 expression invade tumor
      stroma and form metastases. Probably, in such cases, tumor progression is
      stimulated by MMP-15 in an MMP-14 independent pathway, a novel (alternative)
      mechanism.

PMID- 22998429
TI  - Lipoprotein(a): resurrected by genetics.
AB  - Plasma lipoprotein(a) [Lp(a)] is a quantitative genetic trait with a very broad
      and skewed distribution, which is largely controlled by genetic variants at the
      LPA locus on chromosome 6q27. Based on genetic evidence provided by studies
      conducted over the last two decades, Lp(a) is currently considered to be the
      strongest genetic risk factor for coronary heart disease (CHD). The copy number
      variation of kringle IV in the LPA gene has been strongly associated with both
      Lp(a) levels in plasma and risk of CHD, thereby fulfilling the main criterion for
      causality in a Mendelian randomization approach. Alleles with a low kringle IV
      copy number that together have a population frequency of 25-35% are associated
      with a doubling of the relative risk for outcomes, which is exceptional in the
      field of complex genetic phenotypes. The recently identified binding of oxidized
      phospholipids to Lp(a) is considered as one of the possible mechanisms that may
      explain the pathogenicity of Lp(a). Drugs that have been shown to lower Lp(a)
      have pleiotropic effects on other CHD risk factors, and an improvement of
      cardiovascular endpoints is up to now lacking. However, it has been established
      in a proof of principle study that lowering of very high Lp(a) by apheresis in
      high-risk patients with already maximally reduced low-density lipoprotein
      cholesterol levels can dramatically reduce major coronary events.

PMID- 22998428
TI  - Amniotic fluid exhibits an innate inhibitory activity against HIV type 1
      replication in vitro.
AB  - Indirect evidence suggests that amniotic fluid (AF) may play a role in the
      pathogenesis of in utero HIV-1 transmission. The purpose of this study was to
      evaluate the potential innate inhibitory role of AF on HIV replication, which may
      contribute to protection of the fetus against intrauterine transmission. AF was
      collected from term HIV-1-negative women undergoing scheduled cesarean section.
      The inhibitory effect of AF against HIV-1(BA-L) replication was tested in vitro
      with or without the addition of protease inhibitor cocktail (PIC) in PHA
      stimulated PBMC cultures. Quantitative measurement of human neutrophil peptides 1
      3 (HNP1-3) was performed on all AF samples, using an ELISA assay. AF exhibited a
      dose-dependent inhibitory activity against HIV-1(BA-L) replication, with all
      samples (n=12) reaching significant inhibitory effect using 50% AF. In vitro,
      this activity decreased over time, but was able to be sustained with the addition
      of PIC. The HNP1-3 concentration in AF samples (n=12) ranged from undetectable
      (<41 pg/ml, n=3) to >250,000 pg/ml with a median of 5,146 pg/ml. AF exhibited a
      significant and dose-dependent innate inhibitory activity against HIV-1
      replication, which was present in all AF samples tested. This effect was
      prolonged in the presence of PIC, suggesting that the inhibitory factor was in
      the cell-free protein fraction. The HNP1-3 concentration in AF was in the
      subinhibitory range for HIV with no correlation between its concentration and the
      HIV-1 inhibitory activity. These data show the presence of a significant innate
      inhibitory activity against HIV in AF.

PMID- 22998430
TI  - Integrated photo-bioelectrochemical system for contaminants removal and bioenergy
      production.
AB  - An integrated photobioelectrochemical (IPB) system was developed by installing a
      microbial fuel cell (MFC) inside an algal bioreactor. This system achieves the
      simultaneous removal from a synthetic solution of organics (in the MFC) and
      nutrients (in the algal bioreactor), and the production of bioenergy in
      electricity and algal biomass through bioelectrochemical and microbiological
      processes. During the one-year operation, the IPB system removed more than 92% of
      chemical oxygen demand, 98% of ammonium nitrogen, and 82% of phosphate and
      produced a maximum power density of 2.2 W/m(3) and 128 mg/L of algal biomass. The
      algal growth provided dissolved oxygen to the cathode reaction of the MFC,
      whereas electrochemical oxygen reduction on the MFC cathode buffered the pH of
      the algal growth medium (which was also the catholyte). The system performance
      was affected by illumination and dissolved oxygen. Initial energy analysis showed
      that the IPB system could theoretically produce enough energy to cover its
      consumption; however, further improvement of electricity production is desired.
      An analysis of the attached and suspended microbes in the cathode revealed
      diverse bacterial taxa typical of aquatic and soil bacterial communities with
      functional roles in contaminant degradation and nutrient cycling.

PMID- 22998431
TI  - New insights into the brain involvement in patients with Crohn's disease: a voxel
      based morphometry study.
AB  - BACKGROUND: Crohn's disease (CD) is a chronic intestinal disorder characterized
      by overproduction of inflammatory cytokines and recurrent abdominal pain.
      Recently, brain morphological abnormalities in the pain matrix were found in
      patients with chronic pain disorders including irritable bowel syndrome. To
      investigate potential structural brain changes associated with CD, we used
      magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray
      matter (GM) volumes correlated with disease duration. METHODS: Eighteen CD
      patients in remission and 18 healthy controls underwent structural MRI. Voxel
      based morphometry (VBM) is a fully automated technique allowing identification of
      regional differences in the amount of GM enabling an objective analysis of the
      whole brain between groups of subjects. VBM was used for comparisons and
      correlation analysis. KEY RESULTS: With respect to controls, CD patients
      exhibited decreased GM volumes in portion of the frontal cortex and in the
      anterior midcingulate cortex. Disease duration was negatively correlated with GM
      volumes of several brain regions including neocortical and limbic areas.
      CONCLUSIONS & INFERENCES: Crohn's disease is associated with brain morphological
      changes in cortical and subcortical structures involved in nociception,
      emotional, and cognitive processes. Our findings provide new insight into the
      brain involvement in chronic inflammatory bowel disorders.

PMID- 22998432
TI  - Psychological risk factors for poor outcome of spine surgery and spinal cord
      stimulator implant: a review of the literature and their assessment with the MMPI
      2-RF.
AB  - Back pain is experienced by up to of 85% of the United States population. Most
      often it resolves with minimal to no medical treatment. For those whose pain
      endures, worsens, or becomes protracted, conservative care is typically first
      attempted. Individuals who continue to experience significant back pain are often
      considered for surgical procedures, the results of which are not uniformly
      positive. The consequences of failed surgical intervention can be quite
      devastating, and psychosocial factors have been found to predict poor outcome.
      The literature on psychosocial risk factors for failed back surgery is reviewed
      first, identifying psychological dysfunction in the domains of emotions,
      cognitions, behavior, and interpersonal processes as increasing the risk for
      failed back surgery. Empirical findings with the MMPI-2 Restructured Form (MMPI-2
      RF) are presented next, including descriptive analyses with a sample of 1341
      individuals assessed as part of a pre-surgical psychological screening.
      Correlations between MMPI-2-RF scale scores and measures of the primary risk
      factors identified in this review are reported for a smaller sample of 197 pre
      surgical candidates. Interpretive implications of the MMPI-2-RF findings are
      discussed along with suggestions for further research in this area.

PMID- 22998433
TI  - Product channels of the CN + HCNO reaction.
AB  - The kinetics of the reaction of CN radical with fulminic acid (HCNO) was studied
      by transient infrared absorption spectroscopy with the primary goal of resolving
      whether the dominant product channel is NO + HCCN (1a) or HCN + NCO (1b). HCN,
      HCCN, and NO reaction products were directly detected. In some experiments,
      (15)N(18)O reagent was included in the reaction mixtures in order to suppress
      possible secondary chemistry due to NCO radicals. Several other possible
      secondary reactions were also investigated and found to be very slow. The
      resulting product branching fractions of phi(1a) = 0.98 +/- 0.07 for NO + HCCN
      and phi(1b) <= 0.07 for HCN + NCO, respectively, were obtained at 298 K. The
      potential energy surface (PES) of the reaction was calculated by ab initio
      methods at several levels of coupled-cluster theory. The calculations show
      pathways to channels (1a) and (1b) with nearly identical energetics and a
      substantial dependence on the level of theory used, suggesting that
      multireference calculations are needed to accurately predict the experimental
      results.

PMID- 22998434
TI  - Neonatal handling prevents anxiety-like symptoms in rats exposed to chronic mild
      stress: behavioral and oxidative parameters.
AB  - This study investigated the influence of neonatal handling on behavioral and
      biochemical consequences of chronic mild stress (CMS) in adulthood. Male rat pups
      were submitted to daily tactile stimulation (TS) or maternal separation (MS),
      from postnatal day 1 (PND1) to postnatal day 21 (PND21), for 10 min/day. In
      adulthood, half the number of animals were exposed to CMS for 3 weeks and
      submitted to behavioral testing, including sucrose preference (SP), elevated plus
      maze (EPM), and defensive burying tasks (DBTs), followed by biochemical
      assessments. CMS reduced SP, increased anxiety in EPM and DBT, and increased
      adrenal weight. In addition, CMS decreased plasma vitamin C (VIT C) levels and
      increased protein carbonyl (PC) levels, catalase (CAT) activity in hippocampus
      and cortex, and superoxide dismutase (SOD) levels in cortex. In contrast, both
      forms of neonatal handling were able to prevent reduction in SP, anxiety behavior
      in DBT, and CMS-induced adrenal weight increase. Furthermore, they were also able
      to prevent plasma VIT C reduction, hippocampal PC levels increase, CAT activity
      increase in hippocampus and cortex, and SOD levels increase in cortex following
      CMS. Only TS was able to prevent CMS-induced anxiety symptoms in EPM and PC
      levels in cortex. Taken together, these findings show the protective role of
      neonatal handling, especially TS, which may enhance ability to cope with
      stressful situations in adulthood.

PMID- 22998436
TI  - Genomic tillage and the harvest of fungal phytopathogens.
AB  - Genome sequencing has been carried out on a small selection of major fungal
      ascomycete pathogens. These studies show that simple models whereby pathogens
      evolved from phylogenetically related saprobes by the acquisition or modification
      of a small number of key genes cannot be sustained.The genomes show that
      pathogens cannot be divided into three clearly delineated classes (biotrophs,
      hemibiotrophs and necrotrophs) but rather into a complex matrix of categories
      each with subtly different properties. It is clear that the evolution of
      pathogenicity is ancient, rapid and ongoing. Fungal pathogens have undergone
      substantial genomic rearrangements that can be appropriately described as
      'genomic tillage'. Genomic tillage underpins the evolution and expression of
      large families of genes - known as effectors - that manipulate and exploit
      metabolic and defence processes of plants so as to allow the proliferation of
      pathogens.

PMID- 22998437
TI  - Effect of axial ligand on the binding mode of M-meso-tetrakis(N-methylpyridinium
      4-yl)porphyrin to DNA probed by circular and linear dichroism spectroscopies.
AB  - The binding modes of cationic porphyrins, namely M-meso-tetrakis(N
      methylpyridinium-4-yl)porphyrin (MTMPyP, where M = free base, Cu(II), Ni(II),
      Co(III), Mn(III), V(IV)?O, and Ti(IV)?O), to native DNA were systematically
      investigated by polarized light spectroscopies, viz. circular and linear
      dichroism spectroscopy (CD and LD, respectively). At low [porphyrin]/[DNA] ratio,
      planar porphyrins including TMPyP, CuTMPyP, and NiTMPyP exhibited a negative CD
      signal in the Soret region and large negative wavelength-dependent LD(r) signal
      which is characteristics of their intercalative binding mode. In the
      intercalation pocket, the molecular plane of porphyrin is skewed to a large
      extent as it was judged from a large wavelength-dependency of the LD(r) magnitude
      in the Soret region. As the mixing ratio was increased, a bisignate CD spectrum
      became apparent for all of the planar porphyrins, while the shape of LD(r)
      remained the same, indicating the coupling of the electric transition moments of
      the intercalated porphyrins. Thus, coupling can occur between the porphyrins when
      they are separated at least two DNA base-pairs according to the nearest
      neighboring site exclusion model. This coupling interaction was the weakest for
      NiTMPyP. The porphyrins with axial ligands, namely VOTMPyP, TiOTMPyP, MnTMPyP,
      and CoTMPyP, bind to the exterior of the DNA at a low [porphyrin]/[DNA] ratio,
      which is indicated by the positive CD signal in the Soret region. The absorption
      and LD spectra in the Soret region were treated as the sum of two transitions to
      calculate the angle between each of the electric transition moments of the
      porphyrin, i.e., the B(x) and B(y) transitions relative to the local DNA helix
      axis. The angle of one of the two electric transitions of the porphyrin is in the
      range of 56 degrees ~59 degrees , whereas the other is in the range of 59 degrees
      ~65 degrees . Increasing the porphyrin density resulted in the appearance of an
      interaction between the bound porphyrins, which was indicated by the distorted CD
      spectra. In contrast with the planar porphyrins, which are parallel to each other
      in the intercalation pocket when they interact by themselves, the molecular plane
      of the porphyrin with the axial ligand tilts more toward the local DNA helix axis
      as the population of porphyrins was increased. CoTMPyP exhibited complicated CD
      and LD spectra at high [porphyrin]/[DNA] ratios that were impossible to explain
      by the presence of two porphyrin species: those with a monomeric external binding
      and electric coupling. Since the CoTMPyP-DNA complex started to aggregate at
      relatively low [porphyrin]/[DNA] ratios, the complication may due to the
      involvement of extensive porphyrin aggregation.

PMID- 22998435
TI  - Geomagnetic disturbances may be environmental risk factor for multiple sclerosis:
      an ecological study of 111 locations in 24 countries.
AB  - BACKGROUND: We noticed that a hypothesis based on the effect of geomagnetic
      disturbances (GMD) has the ability to explain special features of multiple
      sclerosis (MS). Areas around geomagnetic 60 degree latitude (GM60L) experience
      the greatest amount of GMD. The easiest way to evaluate our hypothesis was to
      test the association of MS prevalence (MSP) with angular distance to geomagnetic
      60 degree latitude (AMAG60) and compare it with the known association of MS with
      geographical latitude (GL). We did the same with angular distance to geographic
      60 degree latitude (AGRAPH60) as a control. METHODS: English written papers with
      MSP keywords, done in Europe (EUR), North America (NA) or Australasia (AUS) were
      retrieved from the PubMed. Geomagnetic coordinates were determined for each
      location and AMAG60 was calculated as absolute value of numerical difference
      between its geomagnetic latitude from GM60L. By an ecological study with using
      meta-regression analyses, the relationship of MSP with GL, AMAG60 and AGRAPH60
      were evaluated separately. MSP data were weighted by square root of number of
      prevalent cases. Models were compared by their adjusted R square (AR2) and
      standard error of estimate (SEE). RESULTS: 111 MSP data were entered in the
      study. In each continent, AMAG60 had the best correlation with MSP, the largest
      AR2 (0.47, 0.42 and 0.84 for EUR, NA and AUS, respectively) and the least SEE.
      Merging both hemispheres data, AMAG60 explained 56% of MSP variations with the
      least SEE (R = 0.75, AR2 = 0.56, SEE = 57), while GL explained 17% (R = 0.41, AR2
      = 0.17, SEE = 78.5) and AGRAPH60 explained 12% of that variations with the
      highest SEE (R = 0.35, AR2 = 0.12, SEE = 80.5). CONCLUSIONS: Our results
      confirmed that AMAG60 is the best describer of MSP variations and has the
      strongest association with MSP distribution. They clarified that the well-known
      latitudinal gradient of MSP may be actually a gradient related to GM60L.
      Moreover, the location of GM60L can elucidate why MSP has parabolic and linear
      gradient in the north and south hemisphere, respectively. This preliminary
      evaluation supported that GMD can be the mysterious environmental risk factor for
      MS. We believe that this hypothesis deserves to be considered for further
      validation studies.

PMID- 22998438
TI  - Isotretinoin treatment in nodulocystic acne with and without polycystic ovary
      syndrome: efficacy and determinants of relapse.
AB  - BACKGROUND: Isotretinoin is the most efficacious long-lasting treatment for acne;
      however, some factors, including polycystic ovary syndrome (PCOS), patient age,
      family history, and type and number of acne lesions, may lead to treatment
      resistance or relapse following treatment. The aim of this study was to compare
      the efficacy and permanence of systemic isotretinoin (SI) in nodulocystic acne
      patients with and without PCOS and to evaluate the factors associated with
      relapse during the first and second post-treatment years. METHODS AND MATERIALS:
      The study included 96 female patients with nodulocystic acne. SI 0.5-1 mg/kg/dl
      was given, with a total cumulative dose of 120-150 mg/kg. Response to treatment
      and relapse during the first and second post-treatment years were evaluated.
      RESULTS: In all, the 50 non-PCOS and 46 PCOS acne patients were similar. SI was
      similarly efficacious in both groups. In total, eight patients relapsed during
      the first post-treatment year, versus 16 during the second. Relapse during the
      first year was associated with the number of nodules at the start of treatment
      and the number of papulopustular lesions at the end of treatment, whereas PCOS,
      patient age, and the number of nodules at the start of treatment were associated
      relapse during the second year. CONCLUSION: Regardless of its association with
      PCOS, SI was effective in the treatment of nodulocystic acne. The factors
      associated with relapse during the 1(st) and 2(nd) post-treatment years differed,
      except for the number of nodules at the start of treatment.

PMID- 22998439
TI  - Prospective randomized controlled trial comparing dynamic hip screw and screw
      fixation for undisplaced subcapital hip fractures.
AB  - BACKGROUND: Neck of femur fractures (NOFFs) are a common cause of morbidity and
      mortality in our community. Minimally displaced intracapsular fractures are
      treated with internal fixation by a two-hole dynamic hip screw (DHS) or three
      partially threaded cancellous screws. Data to support the superiority of one are
      limited. This prospective randomized controlled trial compares outcomes with
      these two fixation methods. METHODS: We prospectively recruited patients over 50
      years, with an acute fracture subcapital NOFF, who walked and lived
      independently, and were cognitively intact. They were randomized into DHS or
      cancellous screw groups and followed up for 2 years (overall 75.9%). Outcomes of
      mortality, revision, loss of fixation, avascular necrosis, surgical
      complications, WOMAC, Harris hip score and SF-12 were measured. RESULTS: We
      recruited 62 patients (31 DHS, 29 cancellous screws, 2 failed consent). Six
      deaths (19.3%) were seen in each group. A total of 3.2% of DHS (1 out of 31) and
      10.3% (3 out of 29) of cancellous screw patients required re-operation (P =
      0.272). There was no statistical significant difference in patient satisfaction,
      quality of life (QoL), radiological union or osteonecrosis. There are trends
      towards better functional scores and QoL in cancellous screws, particularly at 1
      year (P = 0.0061), but with a higher re-operation rate. There was a combined
      mortality and transition to institutional care of 40.0% (24 out of 60) at 2
      years. CONCLUSIONS: This study found no difference in outcomes between DHS and
      cancellous screws in the treatment of subcapital NOFFs in a fit, independent
      population, but we found a high level of physical decline in previously fit,
      independently ambulating patients. A large, multicentre trial will be required to
      differentiate between these two fixation methods.

PMID- 22998441
TI  - Broad-spectrum antimicrobial supramolecular assemblies with distinctive size and
      shape.
AB  - With the increased prevalence of antibiotic-resistant infections, there is an
      urgent need for innovative antimicrobial treatments. One such area being actively
      explored is the use of self-assembling cationic polymers. This relatively new
      class of materials was inspired by biologically pervasive cationic host defense
      peptides. The antimicrobial action of both the synthetic polymers and naturally
      occurring peptides is believed to be complemented by their three-dimensional
      structure. In an effort to evaluate shape effects on antimicrobial materials,
      triblock polymers were polymerized from an assembly directing terephthalamide
      bisurea core. Simple changes to this core, such as the addition of a methylene
      spacer, served to direct self-assembly into distinct morphologies-spheres and
      rods. Computational modeling also demonstrated how subtle core changes could
      directly alter urea stacking motifs manifesting in unique multidirectional
      hydrogen-bond networks despite the vast majority of material consisting of
      poly(lactide) (interior block) and cationic polycarbonates (exterior block). Upon
      testing the spherical and rod-like morphologies for antimicrobial properties, it
      was found that both possessed broad-spectrum activity (Gram-negative and Gram
      positive bacteria as well as fungi) with minimal hemolysis, although only the rod
      like assemblies were effective against Candida albicans.

PMID- 22998440
TI  - Tumour necrosis factor alpha downregulates human hemojuvelin expression via a
      novel response element within its promoter.
AB  - BACKGROUND: Iron homeostasis is chiefly regulated by hepcidin whose expression is
      tightly controlled by inflammation, iron stores, and hypoxia. Hemojuvelin (HJV)
      is a bone morphogenetic protein co-receptor that has been identified as a main
      upstream regulator of hepcidin expression; HJV mutations are associated with a
      severe form of iron overload (Juvenile haemochromatosis). Currently however,
      there is no information on how HJV is regulated by inflammation. METHODS: To
      study the regulation of Hjv expression by inflammation and whether Hfe has a role
      in that regulation, control and LPS-injected wild type and Hfe KO mice were used.
      Moreover, human hepatoma cells (HuH7) were used to study the effect of IL-6 and
      TNF-alpha on HJV mRNA expression. RESULTS: Here we show that LPS repressed
      hepatic Hjv and BMPs, while it induced hepcidin 1 expression in wild-type and Hfe
      KO mice with no effect on hepatic pSMAD 1, 5, 8 protein levels. In addition,
      exogenous TNF-alpha (20 ng/mL) decreased HJV mRNA and protein expression to 40%
      of control with no effect on hepcidin mRNA expression in 24 hours. On the other
      hand, IL-6 induced hepcidin mRNA and protein expression with no effect on HJV
      mRNA expression levels. Moreover, using the HJV promoter-luciferase reporter
      fusion construct (HJVP1.2-luc), we showed that the basal luciferase activity of
      HJVP1.2-luc was inhibited by 33% following TNF-alpha treatment of HuH7
      transfected cells suggesting that the TNF-alpha down-regulation is exerted at the
      transcriptional level. Additionally, mutation of a canonical TNF- alpha
      responsive element (TNFRE) within HJVP1.2-luc abolished TNF-alpha response
      suggesting that this TNFRE is functional. CONCLUSIONS: From these results, we
      conclude that TNF-alpha suppresses HJV transcription possibly via a novel TNFRE
      within the HJV promoter. In addition, the results suggest that the proposed link
      between inflammation and BMP-SMAD signalling is independent of HJV and BMP
      ligands.

PMID- 22998442
TI  - Miliarial-type perifollicular B-cell pseudolymphoma (lymphocytoma cutis): a
      misleading eruption in two women.
AB  - Disseminated miliarial-type lymphocytoma cutis is a rare clinicopathologic
      subtype of lymphocytoma, characterized by numerous translucent micropapules and
      located on the head and neck. We describe here the clinical, histological and
      immunological features of miliarial-type perifollicular B-cell pseudolymphoma in
      two women aged 32 and 49 years presenting with numerous 1-2 mm translucent
      papules on the head and neck. Microscopic examination revealed features typical
      of a miniature lymphocytoma cutis with a superficial nodular infiltrate housing
      small well-circumscribed germinal centers containing tingible body macrophages
      and surrounded by a distinct mantle zone. The immunohistological profile was also
      typical of lymphocytoma cutis, and polymerase chain reaction analysis of the IgH
      gene rearrangement did not show any clonal B-cell population. The lesions
      resolved spontaneously in one case and improved after treatment with
      hydroxychloroquine in the second patient. The presentation of this subtype of
      lymphocytoma is a formidable clinical diagnostic challenge. Rosacea, sarcoidosis,
      democidiosis, lupus miliaris disseminatus faciei and steroid acne are easy to
      exclude on the basis of histological profile. However, the miliarial form of
      primary cutaneous center lymphoma is difficult to rule out. Dermatologists and
      dermatopathologists should be aware of this unusual form of lymphocytoma cutis,
      which can be misleading during clinical diagnosis.

PMID- 22998444
TI  - Incidence and risk factors for endocarditis among patients with health care
      associated Staphylococcus aureus bacteraemia.
AB  - BACKGROUND: Staphylococcus aureus infective endocarditis (IE) is a characteristic
      community-acquired infection, however most cases are presently occurring in the
      health care setting. This study investigated the incidence and risk factors for
      S. aureus IE in patients with nosocomial and health care-associated S. aureus
      bacteraemia (SAB). METHODS: Consecutive patients with health care-associated and
      hospital-acquired SAB were prospectively recruited over a 30-month period.
      Patients were followed up for at least 12 weeks after the initial positive blood
      culture result. The primary endpoint was the diagnosis of IE. RESULTS: IE
      occurred in 11 of 303 patients (3.6%). Patient characteristics at diagnosis and
      that were associated with IE included the number of positive blood cultures
      obtained during hospitalization (p = 0.003), the duration of bacteraemia (p <
      0.001), bacteraemia persisting for > 3 days (odds ratio (OR) 14.5, 95% confidence
      interval (CI) 4.0-52.8; p < 0.001), performance of echocardiography (OR 1.88, 95%
      CI 1.69-2.1; p = 0.001), presence of a well known predisposing risk for IE (OR
      57.2, 95% CI 13.6-240.5; p < 0.001), a non-fatal McCabe score (OR 2.10, 95% CI
      1.4-3.1; p = 0.02), and the duration of fever related to the infection (p =
      0.026). On multivariable analysis, the presence of a predisposing risk for IE,
      prolonged bacteraemia, and non-fatal McCabe score remained significantly
      associated with IE. CONCLUSIONS: In this study the incidence of IE was lower than
      previously reported. Three clinical characteristics were identified as risk
      factors for IE among patients with SAB acquired in a health care setting.

PMID- 22998443
TI  - Selectivity, cocrystal structures, and neuroprotective properties of leucettines,
      a family of protein kinase inhibitors derived from the marine sponge alkaloid
      leucettamine B.
AB  - DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs
      (cdc2-like kinases) are implicated in the onset and development of Alzheimer's
      disease and Down syndrome. The marine sponge alkaloid leucettamine B was recently
      identified as an inhibitor of DYRKs/CLKs. Synthesis of analogues (leucettines)
      led to an optimized product, leucettine L41. Leucettines were cocrystallized with
      DYRK1A, DYRK2, CLK3, PIM1, and GSK-3beta. The selectivity of L41 was studied by
      activity and interaction assays of recombinant kinases and affinity
      chromatography and competition affinity assays. These approaches revealed
      unexpected potential secondary targets such as CK2, SLK, and the lipid kinase
      PIKfyve/Vac14/Fig4. L41 displayed neuroprotective effects on glutamate-induced
      HT22 cell death. L41 also reduced amyloid precursor protein-induced cell death in
      cultured rat brain slices. The unusual multitarget selectivity of leucettines may
      account for their neuroprotective effects. This family of kinase inhibitors
      deserves further optimization as potential therapeutics against neurodegenerative
      diseases such as Alzheimer's disease.

PMID- 22998445
TI  - PI3K mediates stretch-induced COX-2 expression during urinary tract obstruction.
AB  - BACKGROUND AND PURPOSE: Stretch-induced cyclooxygenase-2 (COX-2) expression
      occurs in urothelial cells during urinary tract obstruction (UTO). This increases
      COX-2-dependent prostanoid synthesis in stretched urothelial cells. These
      prostanoids then act on afferent neurons and smooth muscle cells in the ureter to
      amplify nociceptive and contractile responses, respectively. We previously used a
      unilateral ureteral obstruction (UUO) mouse model and a primary human urothelial
      cell (HUC) stretch model to describe ureteral COX-2 expression during UTO. The
      current study was performed to determine whether phosphatidylinositol 3-kinase
      (PI3K)-dependent signaling pathways are necessary for stretch-induced COX-2
      expression in urothelial cells. MATERIALS AND METHODS: Adult male CD-1 mice were
      treated with 25% dimethyl sulfoxide/phosphate buffered saline or PI3K inhibitor
      LY294002 (3 mg/kg, 30 mg/kg) for 1 hour before performing UUO for up to 4 hours.
      Obstructed and contralateral mouse ureters were analyzed via immunohistochemistry
      or Western blotting to assess in vivo stretch-induced COX-2 expression. In
      addition, HUCs were cyclically stretched (5%-20% displacement, 12 cycles/min) on
      collagen I-coated stretch plates and assessed for COX-2 expression via Western
      blotting. RESULTS: Histologic analyses of obstructed ureters show that urothelial
      cells stretch in response to external obstruction, COX-2 expression increases in
      the stretched urothelial cells, and no infiltrating immune cells were present
      under the conditions of the study. PI3K inhibitor LY294002 (30 mg/kg) attenuated
      in vivo stretch-induced COX-2 expression. LY294002 or RNA-interference also
      attenuated (HUC) stretch-induced COX-2 expression in vitro. Furthermore, the
      results also show that LY294002 inhibits stretch-induced protein kinase C
      (PKCzeta) activation previously identified upstream of stretch-induced COX-2
      expression in HUCs. CONCLUSIONS: The results indicate that PI3K is a mediator of
      stretch-induced COX-2 expression in urothelial cells. Identifying molecules that
      couple urothelial cell stretch to COX-2 expression may provide targets of drug
      action for effective therapeutics for UTO.

PMID- 22998446
TI  - Management of high AC/A ratio esotropia.

PMID- 22998447
TI  - An 8-year-old girl with uveitis, untreated increased intraocular pressure, and
      lens opacities.

PMID- 22998448
TI  - Strabismus in spina bifida myelomeningocele.

PMID- 22998449
TI  - Ocular anomalies associated with optic disc pit.

PMID- 22998450
TI  - From aggregation-induced emission of Au(I)-thiolate complexes to ultrabright
      Au(0)@Au(I)-thiolate core-shell nanoclusters.
AB  - A fundamental understanding of the luminescence of Au-thiolate nanoclusters
      (NCs), such as the origin of emission and the size effect in luminescence, is
      pivotal to the development of efficient synthesis routes for highly luminescent
      Au NCs. This paper reports an interesting finding of Au(I)-thiolate complexes:
      strong luminescence emission by the mechanism of aggregation-induced emission
      (AIE). The AIE property of the complexes was then used to develop a simple one
      pot synthesis of highly luminescent Au-thiolate NCs with a quantum yield of ~15%.
      Our key strategy was to induce the controlled aggregation of Au(I)-thiolate
      complexes on in situ generated Au(0) cores to form Au(0)@Au(I)-thiolate core
      shell NCs where strong luminescence was generated by the AIE of Au(I)-thiolate
      complexes on the NC surface. We were able to extend the synthetic strategy to
      other thiolate ligands with added functionalities (in the form of custom-designed
      peptides). The discovery (e.g., identifying the source of emission and the size
      effect in luminescence) and the synthesis protocols in this study can contribute
      significantly to better understanding of these new luminescence probes and the
      development of new synthetic routes.

PMID- 22998451
TI  - P-glycoprotein, breast cancer resistance protein, Organic Anion Transporter 3,
      and Transporting Peptide 1a4 during blood-brain barrier maturation: involvement
      of Wnt/beta-catenin and endothelin-1 signaling.
AB  - Our current knowledge about drug transporters in the maturational brain is very
      limited. In this study, we provide a comprehensive overview of the expression and
      activity profile of P-glycoprotein (P-gp), Breast Cancer Resistance Protein
      (bcrp), Organic Anion Transporter 3 (oat3), and Transporting Peptide 1a4
      (oatp1a4) transporters during blood-brain barrier (BBB) maturation. Gene and
      protein expressions of the analyzed transporters increase as the brain matures,
      with no variation in their activity for P-gp and bcrp, while the transport
      activity of oat3 and oatp1a4 increases during brain maturation from preterm up to
      adulthood. For the first time, we illustrate a downregulation of nuclear beta
      catenin expression in brain capillaries when bcrp, P-gp, oat3, and oatp1a4
      transporters are at their highest expression levels. In vivo activation of beta
      catenin in rat brains, by intracerebroventricular (ICV) injection of a GSK-3
      inhibitor, enhances the activity of P-gp, bcrp, oat3, and oatp1a4. Interestingly,
      in an in vitro BBB model consisting of a coculture of primary endothelial brain
      cells with astrocytes or in vivo, activation of beta-catenin enhances the mRNA
      expression of ET-1. Interestingly, blocking the ETA receptor for endothelin-1 in
      vivo by ICV injection of a ETA antagonist decreases transporter activity mediated
      by the activation of beta-catenin. These findings shed light on the role of an
      interaction between beta-catenin and endothelin-1 signaling in the regulation of
      these transporters at the BBB.

PMID- 22998452
TI  - MUC1 immunotherapy is here to stay.
AB  - INTRODUCTION: Success of HBV vaccines in reducing the incidence of liver cancer,
      and HPV vaccines in reducing preneoplastic cervical lesions, demonstrate the
      potential of cancer reduction by harnessing the immune system. For most human
      cancers, infectious etiology is not known but other tumor antigens, candidates
      for vaccines, have been identified. AREAS COVERED: The authors discuss knowledge
      accumulated the last two decades on the tumor antigen MUC1 that has put it at the
      top of the list as an immunotherapy reagent. They examine evidence that anti-MUC1
      immunity affects tumor development and prognosis. Finally, they review two
      decades of immunotherapy trials targeting MUC1, focusing primarily on vaccines
      but also adoptive antibody and T-cell therapies. EXPERT OPINION: Most approaches
      targeting MUC1 have been immunotherapies administered to date to more than 1200
      patients in clinical trials. Even though these trials focused on advanced cancer,
      encouraging results were reported particularly for less immunosuppressed
      patients. Furthermore, spontaneous anti-MUC1 immune responses are associated with
      better prognosis or with a reduced lifetime risk of developing MUC1+ cancers.
      MUC1 is abnormally expressed in over 80% of all cancers. Successfully targeting
      this molecule could benefit over a million patients diagnosed yearly with MUC1+
      tumors just in the USA.

PMID- 22998453
TI  - Human neutrophil antibodies in a blood donor population: a lookback study.
AB  - BACKGROUND AND OBJECTIVES: Human neutrophil antibodies (HNA) have been associated
      with severe transfusion-related acute lung injury (TRALI). We identified HNA
      antibodies in a blood donor population and performed an observational lookback on
      patients who received products from these donors to determine whether TRALI was
      associated with these transfusions. MATERIALS AND METHODS:   Human neutrophil
      antibodies were determined in 1171 blood donors (388 non-transfused males, 390
      human leucocyte antigen (HLA) antibody-negative females and 393 HLA antibody
      positive females) for IgG and IgM antibodies using a flow cytometric assay.
      Selected positive samples had a monoclonal antibody immobilization of granulocyte
      antigen (MAIGA) and neutrophil genotyping performed to confirm specificity.
      Lookback was performed on patients receiving blood from donors with positive
      samples by extracting recipient data from hospital medical records. An expert
      panel of three pulmonary critical care physicians reviewed the summarized data
      and assigned a diagnosis of TRALI, possible TRALI, cannot distinguish between
      TRALI and TACO, TACO and other. RESULTS: Eight donors had HNA antibodies of which
      five contributed to this lookback (3-HNA-specific antibodies, 2-HNA non-specific
      antibodies). Seventy-six blood products were transfused from these donors into
      individual patients. One patient developed TRALI that was associated with a donor
      with a non-specific HNA antibody as well as class-I and class-II HLA antibodies.
      CONCLUSION: The incidence of TRALI in this lookback was low and combined with low
      frequency of HNA antibodies in the donor population suggests not screening donors
      for HNA antibodies at this time is acceptable.

PMID- 22998454
TI  - Evaluation of factors associated with prolonged hospital stay and outcome of
      febrile neutropenic patients receiving chemotherapy: 70 cases (1997-2010).
AB  - Febrile neutropenia (FN) is an important sequela in veterinary patients receiving
      chemotherapy. The purpose of this study was to identify factors associated with
      prolonged hospital stay and outcome in canine patients developing FN secondary to
      chemotherapy administration. Medical records of 70 dogs treated for FN at the
      University of Pennsylvania from 1997 to 2010 were retrospectively evaluated. The
      mean interval between chemotherapy and hospitalization was 7 days. Two-thirds of
      treated patients had lymphoma. The majority of patients (70%) received
      vincristine or doxorubicin prior to the development of FN. Tachycardia at
      admission, complicating medical issues, G-CSF use and decreasing neutrophil count
      after admission were associated with prolonged hospital stay. Hypotension and G
      CSF use were significantly associated with death in-hospital. Mortality was 8.5%.
      Identification of factors associated with prolonged hospital stay and mortality
      in patients with FN may enable the development of risk-adapted treatment
      guidelines to minimize chemotherapy-associated morbidity and mortality.

PMID- 22998455
TI  - The role of terbinafine in induction and/or exacerbation of psoriasis.

PMID- 22998456
TI  - Topical application of 1% chlorhexidine gel versus 0.2% mouthwash in the
      treatment of peri-implant mucositis. An observational study.
AB  - OBJECTIVE: The aim of this study was to compare the use of two chlorhexidine
      based antimicrobial agents as an adjunct to mechanical therapy for the treatment
      of peri-implant mucositis. MATERIALS AND METHODS: Thirty patients with peri
      implant mucositis were included in the study and randomized in two groups. In
      addition to mechanical therapy, group A was treated with chlorhexidine 0.2%
      mouthwash, while group B was treated with chlorhexidine 1% gel. Probing depth,
      plaque index and bleeding index were recorded at each scheduled follow-up visit:
      ten days, 1 month and 3 months after giving the patients the assigned
      formulation. Patients had to fill in a questionnaire investigating their
      satisfaction and ease of use of the product. RESULTS: A total of 23 patients (13
      in group A and 10 in group B) attended all the follow-up visits. Chlorhexidine
      0.2% mouthwash and chlorhexidine 1% gel were equally useful in the treatment of
      peri-implant mucositis leading to the reduction in inflammatory parameters.
      Probing depth decreased over time in both groups. Patients showed preference for
      gel formulation even if they found it more difficult to use. CONCLUSIONS:
      Adjunctive treatment with different chlorhexidine formulations was beneficial to
      the treatment of peri-implant mucositis. Besides, no differences could be found
      between 0.2% mouthwash and 1% gel.

PMID- 22998457
TI  - Short communication: HIV+ viremic slow progressors maintain low regulatory T cell
      numbers in rectal mucosa but exhibit high T cell activation.
AB  - Viremic slow progressors (VSP) are a rare subset of HIV-infected persons who
      exhibit slow immunologic progression despite high viremia. The mechanisms
      associated with this slow progression remain to be defined. Clinical
      characteristics of VSP are similar to those of natural hosts for simian
      immunodeficiency virus (SIV), such as sooty mangabeys (SM) and African green
      monkeys (AGM), who maintain near-normal CD4 counts despite high-level viremia but
      maintain low immune activation. Immune activation is a powerful predictor of
      disease progression, and we hypothesized that low immune activation might also
      explain the VSP phenotype. Using multiparameter flow cytometry, we assessed
      levels of T cell activation and regulatory T cells (Treg) in blood and rectal
      mucosa of VSP, typical progressors, virologic controllers, and seronegative
      controls. We also assessed Treg function and CD4 T cell proliferative capacity in
      VSP. Contrary to expectations, we found that VSP subjects have high levels of T
      cell activation in the gastrointestinal mucosa. The ratio of Treg to CD3+ T cells
      in the mucosa of VSP was relatively low, potentially contributing to increased
      immune activation. Nonetheless, CD4+CD25- T cells isolated from these individuals
      displayed a comparatively weak proliferative response to anti-CD3 stimulation.
      These data reveal that the VSP phenotype is associated with elevated markers of
      mucosal immune activation and low numbers of mucosal Treg, suggesting that
      factors other than immune activation account for this phenotype.

PMID- 22998458
TI  - Methionine residue acts as a prooxidant in the *OH-induced oxidation of
      enkephalins.
AB  - Enkephalins are bioactive pentapeptides (Tyr-Gly-Gly-Phe-Leu (Leu-enk) and Tyr
      Gly-Gly-Phe-Met (Met-enk)) produced while an organism is under mental and/or
      physical stress. In the course of their biological action they are exposed to
      reactive oxygen and nitrogen species. We have reinvestigated the reactions of
      (*)OH radicals toward these peptides in order to elucidate the oxidation
      mechanisms and the final products. Nanosecond pulse radiolysis was used to obtain
      the spectra of the reaction intermediates and their kinetics. Additional insight
      into details of the oxidation mechanism was gained by identification of main
      final products by means of UV-vis spectrophotometry, HPLC coupled with
      fluorescence spectroscopy, and mass spectrometry. The key processes are different
      in both peptides. In Leu-enk, the first step is an (*)OH radical addition to the
      aromatic rings of Tyr and Phe residues that leads to hydroxylated residues,
      dihydroxyphenylalanine (DOPA) from Tyr and tyrosine isomers from Phe,
      respectively. In Met-enk, these processes are less important, an additional
      target being the sulfur atom of the methionine residue. Depending on pH either an
      OH-adduct (hydroxysulfuranyl radical) or a sulfur radical cation undergo
      intramolecular electron transfer with Tyr residue resulting in a repair of Met
      and oxidation of Tyr to tyrosyl radicals and a final formation of dityrosine. At
      low pH, the OH-adducts to Tyr residue are precursors of tyrosyl radicals and
      dityrosine. Thus, the final products coming from oxidation of the Tyr residue
      depend strongly on the neighboring residues and the pH.

PMID- 22998459
TI  - Electronic structure and spectra of the RbAr van der Waals system including spin
      orbit interaction.
AB  - The potential energy curves and spectroscopic constants of the ground and excited
      states of the RbAr van der Waals system have been determined using a one-electron
      pseudopotential approach. This technique is used to replace the effect of the
      Rb(+) core and the electron-Ar interactions by effective potentials. The core
      core interaction for Rb(+)Ar was incorporated using the accurate CCSD(T)
      potential of Hickling et al. [Hickling, H. L.; Viehland, L. A.; Shepherd, D. T.;
      Soldan, P.; Lee, E. P. F.; Wright, T. G. Phys. Chem. Chem. Phys. 2004, 6, 4233
      4239]. This model reduces the number of active electrons of the RbAr van der
      Waals systems to just the single valence electron, permitting the use of very
      large basis sets for the Rb and Ar atoms. Using this approach, the potential
      energy curves of the ground and excited states dissociating into Rb(5s, 5p, 4d,
      6s, 6p, 6d, and 7s) + Ar are calculated at the SCF level. Spin-orbit interaction
      was also considered within a semiempirical scheme for the states dissociating
      into Rb(5p) and Rb(6p). Spectroscopic constants are derived and compared with the
      available theoretical and experimental data. Such comparisons for RbAr show very
      good agreement for the ground and the first excited states. Furthermore, we have
      predicted the B(2)Sigma(+)(1/2) <- X(2)Sigma(+), A(2)Pi(1/2) <- X(2)Sigma(+),
      A(2)Pi(3/2) <- X(2)Sigma(+), A(2)Pi(3/2) <- X(2)Sigma(+), 5(2)Sigma(+) <-
      X(2)Sigma(+), 3(2)Pi(1/2) <- X(2)Sigma(+), and 3(2)Pi(3/2) <- X(2)Sigma(+)
      absorption spectra.

PMID- 22998460
TI  - Enhanced sensitivity to punctate painful stimuli in female patients with chronic
      low back pain.
AB  - BACKGROUND: Chronic low back pain (CLBP) has been shown to be associated with
      various pathophysiological changes at several level of the sensorimotor system,
      pointing to a general hypersensitivity in CLBP patients. The aim of the present
      study was to investigate signs of generalized mechanical pain hypersensitivity in
      CLBP patients on the hand and on the painful site of the back. METHODS: Pinprick
      stimulation according to a validated standardized quantitative sensory testing
      protocol was used in 14 female CLBP patients and 14 healthy controls (HC) matched
      for sex and age. Stimulus response functions to pinprick stimulation on the skin
      were examined at the affected back and reference sites (hand palmar and hand
      dorsum). Data from CLBP patients were compared with HC and with reference data
      from the German Research Network on Neuropathic Pain. RESULTS: We found
      significant differences in the stimulus response functions between CLBP patients
      and HC. Pain ratings to the pinpricks were increased for low and moderate
      pinprick stimuli in CLBP patients. Importantly, this kind of specific pinprick
      hyperalgesia was found not only for the affected body site (back), but also for
      the remote reference sites (hand dorsum and hand palmar). CONCLUSIONS: We
      interpret our results as pointing to changes in the nociceptive processing in
      CLBP at higher levels of the neuraxis, possibly thalamus and/or attentional
      control, rather than changes of spinal processing. Alternatively, there might be
      a higher vulnerability to noxious stimulation in CLBP patients.

PMID- 22998461
TI  - Plasma rich in growth factors in human extraction sockets: a radiographic and
      histomorphometric study on early bone deposition.
AB  - OBJECTIVES: To determine whether and to what extent the additional application of
      plasma rich in growth factors (PRGF) to an extraction socket may influence the
      early bone deposition, as assessed by micro-computed tomography (micro-CT) scan
      as well as histomorphometric markers. MATERIAL AND METHODS: Twenty-eight patients
      (age range: 34-74 years) contributing 36 extraction sockets were included in the
      study. Sockets were either treated with PRGF (PRGF group; 18 sites in 11
      patients) or left to spontaneous healing (control group; 18 sites in 17
      patients). Radiographic and histomorphometric analysis was performed on bone
      cores trephined from each healing socket after 4-6 (T1) or 7-10 (T2) weeks of
      healing. RESULTS: Patients treated with PRGF application showed (i) similar bone
      volume and tissue mineral content, (ii) a trend, although not statistically
      significant, toward a greater number of CD68+ cells (at T1 and T2) and vVW+ cells
      (at T1), and (iii) a similar OCN staining score throughout the study, when
      compared with control group. CONCLUSIONS: Plasma rich in growth factors-treated
      group did not show any enhancement in early (4 and 8 weeks) bone deposition
      compared with control group.

PMID- 22998462
TI  - Urban legends series: oral candidosis.
AB  - Candida species (spp) are commensal yeast that can only instigate oral infection
      (oral candidosis - OC) when there is an underlying predisposing condition in the
      host. We investigated four controversial topics on OC: (i) How can a
      microbiological determination of OC be made as Candida spp. are commensal yeasts
      and not all of them form hyphae or pseudohyphae during infection? (ii) Is median
      rhomboid glossitis (MRG) a manifestation of candidal infection? (iii) Can
      candidal infection cause palate papillary hyperplasia (PPH)? (iv) What is the
      best therapeutic treatment for denture-associated erythematous stomatitis (DAES)?
      Results from extensive literature searches, including a systematic review,
      suggested the following: (i) the diagnosis of OC merely on the basis of the
      presence of yeasts is an oversimplification of a complex process. No convincing
      evidence of a single test or method better able to discriminate the transition
      from candidal saprophytism to pathogenicity has been reported in the literature;
      (ii-iii) conclusive evidence of a direct aetiopathogenic relationship between MRG
      and PPH and candidal infection has not been found; and (iv) only limited evidence
      is available for any DAES treatment, thus making it impossible to make strong
      therapeutic recommendations. 

PMID- 22998463
TI  - Inflammation and increased myxovirus resistance protein A expression in thyroid
      tissue in the early stages of Hashimoto's thyroiditis.
AB  - BACKGROUND: The role of viruses as environmental triggers for Hashimoto's
      thyroiditis (HT) is controversial. Thyroid epithelial cells express a variety of
      molecules involved in antiviral responses. This study combined histological,
      immunological, and virological tests to describe changes in tissue from patients
      with newly diagnosed and untreated HT. To study the early events, patients with
      positive thyroid peroxidase antibodies (TPO-Ab) and normal thyroid function were
      also included. This stage was defined as "prethyroiditis." METHODS: Thyroid
      tissue was collected from 47 patients with high titers of TPO-Ab and from 24
      controls. Seventeen patients had prethyroiditis, 17 had subclinical
      hypothyroidism, and 13 had overt hypothyroidism. The interferon (IFN)-alpha/beta
      inducible myxovirus resistance protein 1 (myxovirus resistance protein A; MxA)
      was used as a surrogate marker for type I IFN expression. Inflammation,
      expression of MxA, and the presence of the enteroviralcapsid protein (VP1) were
      characterized by immunohistochemistry. The presence of enterovirus (EV) RNA was
      examined by in situ hybridization. RESULTS: The density of CD4+ T cells was
      increased in all three patient groups, while CD8+ T cells were increased only in
      patients with overt hypothyroidism. The density of plasma cells increased as the
      disease progressed. The density of plasmacytoid dendritic cells and the
      expression of MxA were significantly increased in all patient groups compared
      with controls (p<0.01). EV RNA was present in 11% of HT patients, but in none of
      the control subjects, whereas the enteroviral protein was detected in 19% and
      16%, respectively. CONCLUSION: The inflammatory reaction in the thyroid gland is
      a very early event in the pathogenesis of HT. The increased expression of MxA in
      the inflamed tissue suggests that type I IFN plays a role in disease development.
      Whether this is virus-dependent needs to be explored in further studies.

PMID- 22998464
TI  - The effect of insulin intensification in children and young persons with Type 1
      diabetes differs in relation to ethnic group; a prospective observational study.
AB  - AIMS: We prospectively evaluated the effect of insulin intensification on
      glycaemic control and lipid levels in children and young persons with Type 1
      diabetes in relation to ethnicity. METHODS: In the first 2 years of a 3-year
      observation period, as part of routine clinical care, 231 children and young
      persons (40% white, 28% South Asian, 32% black) from a single clinic were offered
      intensive insulin therapy. After 2 years, 222 were on intensive therapy and their
      data were compared between ethnic groups at the end of year 3. RESULTS: We
      observed ethnic differences in HbA(1c) levels during the study [study beginning
      and end: white children and young persons 77 and 70 mmol/mol (9.2 and 8.6%) vs.
      South Asian 72 and 68 mmol/mol (8.7 and 8.4%) vs. black 83 and 79 mmol/mol (9.7
      and 9.4%), P-value for ANCOVA = 0.007]. By study end, South Asians had the lowest
      HDL cholesterol (2.0 vs. 1.4 vs. 1.6 mmol/l, P-value = 0.03) and highest
      triglyceride levels (0.9 vs. 1.8 vs. 1.0 mmol/l, P-value = 0.001). In linear
      mixed modelling, after adjustment for socio-economic deprivation and other
      covariates: (1) black ethnicity was associated with poorer glycaemic control (P <
      0.001) and (2) South Asian ethnicity was associated with higher triglyceride
      levels (P < 0.001), independent of HbA(1c). CONCLUSIONS: The effect of insulin
      intensification on glycaemic control and lipid profile in children and young
      persons with Type 1 diabetes differs in relation to ethnic group.

PMID- 22998465
TI  - Emergent effects of multiple predators on prey survival: the importance of
      depletion and the functional response.
AB  - The combined effects of multiple predators often cannot be predicted from their
      independent effects. Emergent multiple predator effects (MPEs) include risk
      enhancement, where combined predators kill more prey than predicted by their
      individual effects, and risk reduction, where fewer prey are killed than
      predicted. Current methods for detecting MPEs are biased because they assume
      linear functional responses and/or no prey depletion. As a result, past studies
      overestimated the occurrence of risk enhancement for additive designs, and tended
      to overestimate the occurrence of risk reduction for substitutive designs.
      Characterising the predators' functional responses and accounting for prey
      depletion reduces biases in detection, estimation, interpretation and
      generalisation of the emergent effects of predator diversity on prey survival.
      These findings have implications beyond MPE's and should be considered in all
      studies aimed at understanding how multiple factors combine when demographic
      rates are density dependent.

PMID- 22998466
TI  - Role of reactive oxygen species in Escherichia coli inactivation by cupric ion.
AB  - This study demonstrated Escherichia coli inactivation by cupric ion (Cu[II]),
      focusing on intracellular generation and consumption of reactive oxygen species
      (ROS) including superoxide and hydroxyl radials. In the presence of Cu(II),
      intracellular superoxide levels of E. coli decreased in a concentration-dependent
      manner, indicating that superoxide radical was used to reduce Cu(II) to Cu(I) in
      cells. The variation in the hydroxyl radical level by adding Cu(II) was
      negligible. Molecular oxygen and hydroxyl radical scavengers did not affect the
      inactivation efficacy of E. coli by Cu(II), excluding the possibility that
      hydroxyl radicals induced by the copper-mediated reduction of oxygen contributed
      to the microbiocidal action of Cu(II). However, the inactivation of E. coli by
      Cu(II) was considerably inhibited and accelerated by a Cu(I)-chelating agent and
      a Cu(II)-reducing agent, respectively. Our results suggest that the microbiocidal
      action of Cu(II) is attributable to the cytotoxicity of cellularly generated
      Cu(I), which does not appear to be associated with oxidative damage by Cu(I)
      driven ROS.

PMID- 22998467
TI  - Carbon partitioning in soybean (Glycine max) leaves by combined (11) C and (13) C
      labeling.
AB  - We labeled soybean (Glycine max) leaves with 200 and 600 ppm (13) CO(2)  spiked
      with (11) CO(2)  and examined the effects of light intensity and water stress on
      metabolism by using a combination of direct positron imaging and solid-state (13)
      C nuclear magnetic resonance (NMR) of the same leaf. We first made 60-min movies
      of the transport of photosynthetically assimilated (11) C labels. The positron
      imaging identified zones or patches within which variations in metabolism could
      be probed later by NMR. At the end of each movie, the labeled leaf was frozen in
      liquid nitrogen to stop metabolism, the leaf was lyophilized, and solid-state NMR
      was used either on the whole leaf or on various leaf fragments. The NMR analysis
      determined total (13) C incorporation into sugars, starch, proteins, and protein
      precursors. The combination of (11) C and (13) C analytical techniques has led to
      three major conclusions regarding photosynthetically heterogeneous soybean
      leaves: transient starch deposition is not the temporary storage of sucrose
      excluded from a saturated sugar-transport system; peptide synthesis is reduced
      under high-light, high CO(2)  conditions; and all glycine from the
      photorespiratory pathway is routed to proteins within photosynthetically active
      zones when the leaf is water stressed and under high-light and low CO(2) 
      conditions.

PMID- 22998468
TI  - Plasmon-induced doping of graphene.
AB  - A metallic nanoantenna, under resonant illumination, injects nonequilibrium hot
      electrons into a nearby graphene structure, effectively doping the material. A
      prominent change in carrier density was observed for a plasmonic antenna
      patterned graphene sheet following laser excitation, shifting the Dirac point, as
      determined from the gate-controlled transport characteristic. The effect is due
      to hot electron generation resulting from the decay of the nanoantenna plasmon
      following resonant excitation. The effect is highly tunable, depending on the
      resonant frequency of the plasmonic antenna, as well as on the incident laser
      power. Hot electron-doped graphene represents a new type of hybrid material that
      shows great promise for optoelectronic device applications.

PMID- 22998469
TI  - Inborn errors of metabolism causing epilepsy.
AB  - Seizures may be the first and the major presenting feature of an inborn error of
      metabolism (IEM), for example in a neonate with pyridoxine-dependent epilepsy. In
      other IEMs, seizures may be preceded by other major symptoms: by a reduced level
      of consciousness in a child with an organic acidaemia or urea cycle defect; or by
      loss of skills, progressive weakness, ataxia, and upper motor signs in a child
      with a lysosomal storage disorder or peroxisomal leukodystrophy. This review
      concentrates on those IEMs for which specific treatment is available. The common
      metabolic causes of seizures vary according to the age at presentation. Features
      from the history, examination, imaging, and first line biochemical investigations
      can all provide clues to an inborn error. This review attempts to delineate these
      and to provide a guide to the specific tests that can be used to make the
      diagnosis of disorders with specific treatment.

PMID- 22998470
TI  - The impact of increasing the upper age limit of donation on the eligible blood
      donor population in Canada.
AB  - OBJECTIVES: Using population prevalence data for deferrable diseases/conditions
      we estimated the Canadian population eligible to donate according to three upper
      age limit scenarios. BACKGROUND: The donor selection criteria limit the number of
      potential blood donors but relaxing the upper age criteria could mitigate this.
      METHODS AND MATERIALS: Forty deferral criteria were identified and their
      corresponding prevalence data obtained to estimate the number of people excluded
      by the criteria. The eligible blood donor population was estimated from national
      census data taking the age limits, deferral criteria and deferral time-period
      into account. As more than one disease/condition may co-exist, the estimate was
      adjusted to avoid over-representation. RESULTS: Of about 33 million Canadians
      aged 17 (18 in Quebec) to 65, 15.1 million (45.8%) are eligible to donate blood.
      This number increases to 15.7 million when including people up to 71 years and to
      17.1 million in the absence of an upper age limit. CONCLUSION: As about 1.2
      million units are collected from 600,000 donors annually, there are more than
      enough eligible people to meet the need. However, recruitment of donors is
      challenging and the absence of an upper age limit allows an additional 2 million
      people to donate. Other countries may wish to consider modification of the upper
      age criterion to address the effect of an aging population on the blood supply.

PMID- 22998471
TI  - Graph rigidity reveals well-constrained regions of chromosome conformation
      embeddings.
AB  - BACKGROUND: Chromosome conformation capture experiments result in pairwise
      proximity measurements between chromosome locations in a genome, and they have
      been used to construct three-dimensional models of genomic regions, chromosomes,
      and entire genomes. These models can be used to understand long-range gene
      regulation, chromosome rearrangements, and the relationships between sequence and
      spatial location. However, it is unclear whether these pairwise distance
      constraints provide sufficient information to embed chromatin in three
      dimensions. A priori, it is possible that an infinite number of embeddings are
      consistent with the measurements due to a lack of constraints between some
      regions. It is therefore necessary to separate regions of the chromatin structure
      that are sufficiently constrained from regions with measurements that do not
      provide enough information to reconstruct the embedding. RESULTS: We present a
      new method based on graph rigidity to assess the suitability of experiments for
      constructing plausible three-dimensional models of chromatin structure.
      Underlying this analysis is a new, efficient, and accurate algorithm for finding
      sufficiently constrained (rigid) collections of constraints in three dimensions,
      a problem for which there is no known efficient algorithm. Applying the method to
      four recent chromosome conformation experiments, we find that, for even
      stringently filtered constraints, a large rigid component spans most of the
      measured region. Filtering highlights higher-confidence regions, and we find that
      the organization of these regions depends crucially on short-range interactions.
      CONCLUSIONS: Without performing an embedding or creating a frequency-to-distance
      mapping, our proposed approach establishes which substructures are supported by a
      sufficient framework of interactions. It also establishes that interactions from
      recent highly filtered genome-wide chromosome conformation experiments provide an
      adequate set of constraints for embedding. Pre-processing experimentally observed
      interactions with this method before relating chromatin structure to biological
      phenomena will ensure that hypothesized correlations are not driven by the
      arbitrary choice of a particular unconstrained embedding. The software for
      identifying rigid components is GPL-Licensed and available for download at
      http://cbcb.umd.edu/kingsford-group/starfish.

PMID- 22998472
TI  - Enhanced in vitro biological activity of synthetic 2-(2-pyridyl) ethyl
      isothiocyanate compared to natural 4-(methylsulfinyl) butyl isothiocyanate.
AB  - Dietary isothiocyanates (ITC) derived from cruciferous vegetables have been shown
      to have numerous biological effects consistent with chemoprotective activity. In
      this study we synthesized a novel ITC, 2-(2-pyridyl) ethyl ITC (PY-ITC), and
      assessed its chemopreventive ability in comparison to sulforaphane (SF), the ITC
      derived from broccoli. PY-ITC suppressed cancerous cell growth and proliferation
      at lower concentrations than SF and was more potent at inducing p21 protein.
      Through the use of whole genome arrays we demonstrate that prostate cells exposed
      to PY-ITC or SF have similar biological response, albeit PY-ITC alters a greater
      number of genes, and to a greater extent. In the presence of a
      phosphatidylinositol-3-kinase (PI3K) inhibitor PY-ITC had a more pronounced
      effect on gene expression, emphasizing the important role of PI3K/AKT signaling
      in mediating the chemopreventive effects of ITCs. These results highlight the
      importance of the ITC side chain in bioactivity.

PMID- 22998473
TI  - Cyclic peptide-capped gold nanoparticles as drug delivery systems.
AB  - A number of cyclic peptides were synthesized and evaluated as simultaneous
      reducing and capping agents for generation of cyclic peptide-capped gold
      nanoparticles (CP-AuNPs). Among them, direct dissolution of cyclic peptides
      containing alternate arginine and tryptophan [WR](n) (n = 3-5) into an aqueous
      solution of AuCl(4)(-) led to the formation of CP-AuNPs, through the reducing
      activity of tryptophan residues and attraction of positively charged arginine
      residues toward chloroaurate anions in the reaction environment. Differential
      interference contrast microscopy of fluorescence-labeled lamivudine in the
      presence of [WR](4)-capped AuNPs showed significantly higher cellular delivery of
      antiviral drug versus that of parent drug alone. Flow cytometry studies also
      showed that the cellular uptake of fluorescence-labeled lamivudine,
      emtricitabine, and stavudine was significantly enhanced in human ovarian
      adenocarcinoma (SK-OV-3) cells in the presence of [WR](4)-AuNPs. For example,
      fluorescence labeled lamivudine-loaded [WR](4)-AuNPs exhibited approximately 12-
      and 15-times higher cellular uptake than that of fluorescence labeled lamivudine
      alone in CCRF-CEM cells and SK-OV-3 cells, respectively. Confocal microscopy
      revealed that the presence of the [WR](4)-AuNPs enhanced the retention and
      nuclear localization of doxorubicin in SK-OV-3 cells after 24 h. These data
      suggest that these complexes can be used as potential noncovalent prodrugs for
      delivery of antiviral and anticancer agents.

PMID- 22998474
TI  - Motor neuron disease and acquired axonal neuropathy association in HIV infection:
      case report and update.
AB  - BACKGROUND: A possible viral etiology has been documented in the genesis of motor
      neuron disorders and acquired peripheral neuropathies, mainly due to the
      vulnerability of peripheral nerves and the anterior horn to certain viruses. In
      recent years, several reports show association of HIV infection with Amyotrophic
      Lateral Sclerosis - Syndrome, Motor Neuron Diseases and peripheral neuropathies.
      OBJECTIVE: To report a case of an association between Motor Neuron Disease and
      Acquired Axonal neuropathy in HIV infection, and describe the findings of
      neurological examination, cerebrospinal fluid, neuroimaging and
      electrophysiology. METHODS: The patient underwent neurological examination.
      General medical examinations were performed, including, specific neuromuscular
      tests, analysis of cerebrospinal fluid, muscle biopsy and imaging studies.
      RESULTS AND DISCUSSION: The initial clinical presentation of our case was marked
      by cramps and fasciculations with posterior distal paresis and atrophy in the
      left arm. We found electromyography tracings with deficits in the anterior horn
      of the spinal cord and peripheral nerves. Dysphagia and release of primitive
      reflexes were also identified. At the same time, the patient was informed to be
      HIV positive with high viral load. He received antiretroviral therapy, with load
      control but with no clinical remission. CONCLUSION: Motor Neuron disorders and
      peripheral neuropathy may occur in association with HIV infection. However, a
      causal relationship remains uncertain. It is noteworthy that the antiretroviral
      regimen may be implicated in some cases.

PMID- 22998475
TI  - Clinical outcomes of image guided radiation therapy (IGRT) with gold fiducial
      vaginal cuff markers for high-risk endometrial cancer.
AB  - OBJECTIVE: To report two year clinical outcomes of image guided radiation therapy
      (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk
      endometrial cancer patients. METHODS: Twenty-six consecutive high-risk
      endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and
      regional lymph nodes were treated with vaginal cuff fiducial-based IGRT.
      Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich
      technique. Brachytherapy followed external radiation in 11 patients to a median
      dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy
      in 25 fractions. RESULTS: All 656 fractions were successfully imaged and treated.
      The median overall translational shift required for correction was 9.1 mm
      (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos.
      Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of
      patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in
      eight patients (30%) and grade 3 toxicity occurred in one. At two years, there
      have been no local or regional failures and actuarial overall survival is 95%.
      CONCLUSION: Daily image guidance for high-risk endometrial cancer results in a
      low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor
      control at two years. Vaginal cuff translations can be substantial and may
      possibly result in underdosing if not properly considered.

PMID- 22998476
TI  - Treatment of BRAF inhibitor-induced hyperkeratosis.

PMID- 22998477
TI  - Current challenges in clinical target volume definition: tumour margins and
      microscopic extensions.
AB  - Determination of optimal clinical target volume (CTV) margins around gross tumour
      volume (GTV) for modern radiotherapy techniques, requiring more precise target
      definitions, is controversial and complex. Tumour localisation has been greatly
      improved using molecular imaging integrated with conventional imaging techniques.
      However, the exact incidence and extent of microscopic disease, to be encompassed
      by CTV, cannot be visualised by any techniques developed to date and remain
      uncertain. As a result, the CTV is generally determined by clinicians based on
      their experience and patients' histopathological data. In this article we review
      histopathological studies addressing the extent of subclinical disease and its
      possible correlation with tumour characteristics in various tumour sites. The
      data have been tabulated to facilitate a comparison between proposed margins by
      different investigations and with current margins generally accepted for each
      tumour site. It is concluded that there is a need for further studies to reach a
      consensus on the optimal CTV pertaining to each tumour site.

PMID- 22998478
TI  - Non-amyloid and amyloid prion protein deposits in prion-infected mice differ in
      blockage of interstitial brain fluid.
AB  - AIMS: Prion diseases are characterized by brain deposits of misfolded aggregated
      protease-resistant prion protein (PrP), termed PrPres. In humans and animals,
      PrPres is found as either disorganized non-amyloid aggregates or organized
      amyloid fibrils. Both PrPres forms are found in extracellular spaces of the
      brain. Thus, both might block drainage of brain interstitial fluid (ISF). The
      present experiments studied whether ISF blockage occurred during amyloid and/or
      non-amyloid prion diseases. METHODS: Various-sized fluorescein-labelled ISF
      tracers were stereotactically inoculated into the striatum of adult mice. At
      times from 5 min to 77 h, uninfected and scrapie-infected mice were compared.
      C57BL/10 mice expressing wild-type anchored PrP, which develop non-amyloid PrPres
      similar to humans with sporadic Creutzfeldt-Jakob disease, were compared with
      Tg44+/+ mice (transgenic mice secreting anchorless PrP) expressing anchorless
      PrP, which develop amyloid PrPres similar to certain human familial prion
      diseases. RESULTS: In C57BL/10 mice, extensive non-amyloid PrPres aggregate
      deposition was not associated with abnormal clearance kinetics of tracers. In
      contrast, scrapie-infected Tg44+/+ mice showed blockage of tracer clearance and
      colocalization of tracer with perivascular PrPres amyloid. CONCLUSIONS: As tracer
      localization and clearance was normal in infected C57BL/10 mice, ISF blockage was
      not an important pathogenic mechanism in this model. Therefore, ISF blockage is
      unlikely to be a problem in non-amyloid human prion diseases such as sporadic
      Creutzfeldt-Jakob disease. In contrast, partial ISF blockage appeared to be a
      possible pathogenic mechanism in Tg44+/+ mice. Thus this mechanism might also
      influence human amyloid prion diseases where expression of anchorless or mutated
      PrP results in perivascular amyloid PrPres deposition and cerebral amyloid
      angiopathy.

PMID- 22998479
TI  - Comparison of antigen and two molecular methods for the detection of Clostridium
      difficile toxins.
AB  - BACKGROUND: Clostridium difficile (CD) is considered an important cause of
      diarrhoea associated with the antimicrobial treatment of infections. The
      pathogenicity of CD is due to toxins A and B, produced by toxigenic CD strains.
      METHODS: We evaluated 3 methods for detecting CD toxins: the RIDASCREEN(r) enzyme
      immunoassay (EIA) (R-Biopharm)--one detecting toxins directly in the stool
      specimens and another detecting toxins from isolated CD strains--and 2 molecular
      methods, the illumigeneTM loop-mediated isothermal amplification (LAMP) assay
      (Meridian) and RIDA(r)GENE polymerase chain reaction (PCR) assay (R-Biopharm), as
      direct identification methods from stool specimens. Toxigenic culture (TC) was
      used as the reference method. RESULTS: Altogether 884 stool samples were
      analyzed, of which 253 (29%) were positive by TC. Six hundred and seventy-two
      specimens were tested by RIDASCREEN EIA, 430 were tested with the illumigene LAMP
      assay, and 212 were tested with the RIDA GENE PCR assay. CD toxin A and B antigen
      tests by EIA were very insensitive, both directly from stool specimens (2 series;
      57-61%) and in isolated CD strains (53%); consequently the negative predictive
      value remained low (84-93% and 91%, respectively). Specificity, however, was very
      good at 98-100%. The 2 molecular methods detected CD toxin genes excellently and
      equally, resulting in sensitivities, specificities, and positive and negative
      predictive values of 98%, 100%, 100%, and 98%, respectively. CONCLUSIONS: Both
      molecular assays were easy to use, rapid, sensitive, and specific for the
      detection of toxigenic CD strains.

PMID- 22998480
TI  - Interdiction of a blood donation containing varicella-zoster virus by donor self
      report of chickenpox.
AB  - Nowadays, risk of transfusion-transmitted infection has been substantially
      minimized by stringent donor eligibility screening and infectious disease
      testing. However, we report an interdiction of a blood donation containing
      varicella-zoster virus (VZV) by donor self-reporting of chickenpox. The donor
      developed varicella infection shortly after blood donation despite vaccination.
      Varicella-zoster virus DNA was detected in her fresh-frozen plasma before the
      blood components were issued for clinical transfusion. The report indicates the
      importance of donors' education and awareness of their obligation to report any
      symptoms developed shortly after blood donation in order to further secure blood
      safety. 

PMID- 22998481
TI  - Letter to the Editor: The ezetimibe 'controversy' is a misunderstanding.

PMID- 22998482
TI  - Current treatment of cutaneous squamous cancer and molecular strategies for its
      sensitization to new target-based drugs.
AB  - INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is considered one of the
      most common skin malignancy with a relatively high risk of metastasis occurrence.
      AREAS COVERED: We discuss the pathogenetic mechanisms of cSCC and the main
      therapeutic strategies available for the treatment of cSCC. EXPERT OPINION:
      Chemotherapy and biological therapy with Interferon alpha (IFN-alpha) and cis
      retinoic acid are active but give limited results. Recently, strategies based on
      the use of molecularly target-based agents (MTA) have been used with promising
      results. Based on the available findings, we hypothesize that SCC cells can
      develop survival and resistance mechanisms to MTAs. The detection of these
      mechanisms could be useful in designing strategies able to overcome the latter
      and to potentiate the anticancer activity of MTAs. We describe the example of the
      EGF-dependent survival pathway elicited by IFN-alpha and the different strategies
      to abrogate this survival pathway. Other strategies to potentiate the antitumor
      activity of cytotoxic agents such as docetaxel or cisplatin are also discussed.
      Illuminating examples are the inhibition of multichaperone activity or the
      inactivation of the proteasome. In conclusion, a new dawn based upon the
      rationale use of MTAs is rising up in the treatment of advanced cSCC.

PMID- 22998483
TI  - Endovascular coiling versus neurosurgical clipping in patients with unruptured
      intracranial aneurysm: a systematic review.
AB  - BACKGROUND: To compare the effects of endovascular coiling and neurosurgical
      clipping in patients with unruptured intracranial aneurysm. METHODS: Sixteen
      electronic databases were searched for articles published between 1950 and July
      2010 to compare clinical outcomes of clipping and coiling. Researchers reviewed
      all searched articles and extracted data independently. The quality of studies
      and evidence were evaluated using MINORS and GRADEprofiler, respectively. The
      odds ratio (OR) was calculated using the inverse variance meta-analysis method
      for each study outcome. To assess heterogeneity of ORs across cohorts, Cochran's
      Q statistic and I2 were used. RESULTS: Of 4160 studies, 24 were identified (n =
      31865). Clipping resulted in significantly higher disability using the Glasgow
      Outcome Scale (OR, 2.38; 95% CI, 1.33-4.26) and Modified Rankin Scale (OR, 2.83;
      95% CI, 1.42-5.63) when compared with coiling. ORs for complications were also
      higher with clipping (ORs for neurological and cardiac complications were 1.94
      with a 95% confidence interval [CI] of 1.09-3.47 and 2.51 with a 95% CI of 1.15
      5.50). Clipping resulted in significantly greater disability in the short term
      (<=6 m)(OR on the Glasgow Outcome Scale, 2.72; 95% CI, 1.16-6.34), but not in the
      long term (>6 m)(OR for Glasgow Outcome Scale, 2.12; 95% CI, 0.93-4.84).
      CONCLUSIONS: Coiling was a better procedure for treatment of unruptured
      intracranial aneurysm in terms of disability, complications, especially in the
      short term. Because of the limitations of the reviewed studies, further studies
      are required to support the present results.

PMID- 22998484
TI  - Social interactions of students with disabilities who use augmentative and
      alternative communication in inclusive classrooms.
AB  - The purpose of this study was to explore the naturally occurring social
      interactions for students with disabilities who use augmentative and alternative
      communication (AAC) in general education classrooms. We observed 16 students who
      used AAC and received services under the categories of autism or intellectual
      disability. Participants primarily interacted with their support personnel and
      infrequently conversed with peers despite often being in close proximity. Few
      interaction episodes were initiated by students who used AAC, and initiations to
      peers and adults appeared to serve somewhat different functions. Students with
      disabilities relied more heavily on facial expressions and gestures than on the
      use of their AAC devices. Recommendations for promoting interaction opportunities
      among students are offered, and future research directions are suggested.

PMID- 22998485
TI  - Candidate socioemotional remediation program for individuals with intellectual
      disability.
AB  - The authors developed a computerized program, Vis-a-Vis (VAV), to improve
      socioemotional functioning and working memory in children with developmental
      disabilities. The authors subsequently tested whether participants showed signs
      of improving the targeted skills. VAV is composed of three modules: Focus on the
      Eyes, Emotion Recognition and Understanding, and Working Memory. Ten children
      with idiopathic developmental delay completed four 20-min weekly sessions of VAV
      for 12 weeks with an adult. Participants were evaluated before (Time 0) and after
      (Time 1) training and 6 months after remediation (Time 2). Subjects improved on
      all three modules during training and on emotion recognition and nonverbal
      reasoning post-VAV. These gains were still present at Time 2. VAV is a promising
      new tool for working on socioemotional impairments in hard-to-treat pediatric
      populations.

PMID- 22998487
TI  - Financial well-being of single, working-age mothers of children with
      developmental disabilities.
AB  - Understanding the financial well-being of single mothers who care for children
      with developmental disabilities is important to ensure that public policies can
      be effectively targeted to support these vulnerable families. The authors analyze
      data from the Survey of Income and Program Participation to describe income
      poverty, asset poverty, income, net worth, and liquid assets of U.S. single,
      working-age mothers (n  =  242) of children and adult children with developmental
      disabilities. The well-being of these mothers was compared to the situation of
      married mothers of children with developmental disabilities (n  =  345) and of
      single mothers who did not have children with developmental disabilities (n  = 
      6,547). Compared with both married mothers of children with developmental
      disabilities and single mothers without children with developmental disabilities,
      single mothers of children with developmental disabilities had markedly worse
      financial well-being across a range of income- and asset-based measures. Single
      mothers caring for children with developmental disabilities face adverse
      financial well-being as compared with other mothers. Policy makers should
      consider targeted measures to improve the financial well-being of these parents.

PMID- 22998486
TI  - Perseveration in the connected speech of boys with Fragile X syndrome with and
      without autism spectrum disorder.
AB  - Verbal perseveration is a frequently reported language characteristic of males
      with Fragile X syndrome and may be a defining feature or hallmark of the
      syndrome. We compared the verbal perseveration of boys with Fragile X syndrome
      with (n  =  29) and without (n  =  30) autism spectrum disorder, boys with Down
      syndrome (n  =  27), and typically developing boys (n  =  25) at similar
      nonverbal mental ages. During a social interaction, boys with both Fragile X
      syndrome and autism spectrum disorder produced significantly more topic
      perseveration than all other groups. In social interaction as compared to
      narration, boys with Fragile X syndrome (regardless of autism status) produced
      significantly more topic perseveration. These findings suggest that autism
      status, as well as language sampling context, affect perseveration in boys with
      Fragile X syndrome.

PMID- 22998488
TI  - Using response-prompting procedures during small-group direct instruction:
      outcomes and procedural variations.
AB  - Research was reviewed on small-group instruction for learners with disabilities.
      The review was conducted for articles published between 1990 and 2010 on the
      application of small-group direct instruction to teach discrete skills using
      prompting procedures. A total of 47 articles with 197 participants and 687
      replications of effects was located. Small-group instruction was effective for
      195 of 197 participants and across variations in implementation and contexts.
      Implementers were primarily special education personnel, and instruction
      typically occurred in special education settings. Rigorous designs were used in
      all studies, and fidelity was assessed in 46 of 47 studies and was uniformly
      high. Students consistently reached criterion on their own target behaviors,
      generalized those behaviors, maintained them, and learned the behaviors taught to
      their peers (when this was measured, which occurred in a majority of the
      studies). Future research should examine comparisons of procedural variables and
      promoting social behaviors between group mates.

PMID- 22998491
TI  - Electronic structure of the lowest triplet state of flavin mononucleotide.
AB  - The electronic structure of flavin mononucleotide (FMN), an organic cofactor that
      plays a role in many important enzymatic reactions, has been investigated by
      electron paramagnetic resonance (EPR) spectroscopy, optical spectroscopy, and
      quantum chemistry. In particular, the triplet state of FMN, which is paramagnetic
      (total spin S = 1), allows an investigation of the zero field splitting
      parameters D and E, which are directly related to the two singly occupied
      molecular orbitals. Triplet EPR spectra and optical absorption spectra at
      different pH values in combination with time dependent density functional theory
      (TDDFT) reveal that the highest occupied orbital (HOMO) and lowest unoccupied
      orbital (LUMO) of FMN are largely unaffected by changes in the protonation state
      of FMN. Rather, the orbital structure of the lower lying doubly occupied orbitals
      changes dramatically. Additional EPR experiments have been carried out in the
      presence of AgNO(3), which allows the formation of an Ag-FMN triplet state with
      different zero field splitting parameters and population and depopulation rates.
      Addition of AgNO(3) only induces small changes in the optical spectrum,
      indicating that the Ag(+) ion only contributes to the zero field splitting by
      second order spin-orbit coupling and leaves the orbital structure unaffected. By
      a combination of the three employed methods, the observed bands in the UV/vis
      spectra of FMN at different pH values are assigned to electronic transitions.

PMID- 22998492
TI  - Potential involvement of collagen-binding proteins of Streptococcus mutans in
      infective endocarditis.
AB  - OBJECTIVE: Streptococcus mutans, a major pathogen of dental caries, is considered
      to be one of the causative agents of infective endocarditis (IE). Two types of
      cell surface collagen-binding proteins, Cnm and Cbm, have been identified in the
      organism. The aim of the present study was to analyze these proteins as possible
      etiologic factors for IE. MATERIALS AND METHODS: The binding activities of S.
      mutans strains to collagen types I, III, and IV were analyzed relative to the
      presence of Cnm and Cbm, as were their adhesion and invasion properties with
      human umbilical vein endothelial cells (HUVEC). In addition, distributions of the
      genes encoding Cnm and Cbm in S. mutans-positive heart valve specimens extirpated
      from IE and non-IE patients were analyzed by PCR. RESULTS: Most of the Cbm
      positive strains showed higher levels of binding to type I collagen as well as
      higher rates of adhesion and invasion with HUVEC as compared to the Cnm-positive
      strains. Furthermore, the gene encoding Cbm was detected significantly more
      frequently in heart valve specimens from IE patients than from non-IE patients.
      CONCLUSIONS: These results suggest that the collagen-binding protein Cbm of S.
      mutans may be one of the potential important factor associated with the
      pathogenesis of IE.

PMID- 22998493
TI  - Protective effects of D-limonene on lipid peroxidation and antioxidant enzymes in
      streptozotocin-induced diabetic rats.
AB  - The aim of this study was to evaluate the protective effects of D-limonene on the
      levels of lipid peroxidation by-products and antioxidant defence systems in the
      plasma and tissues of normal and streptozotocin (STZ)-induced diabetes rats. The
      experimental diabetes was induced in rats by a single dose of STZ (40 mg/kg i.p.)
      injection, and treatment with D-limonene was continued for 45 days. After the
      treatment period, oxidative stress parameters such as lipid peroxidation by
      products; enzymatic antioxidants such as superoxide dismutase, catalase,
      glutathione peroxidase and glutathione-S-transferase; non-enzymic antioxidants
      including reduced glutathione, Vitamins C and E were measured in the plasma and
      tissues of experimental rats. An increase in the levels of lipid peroxidation by
      products and significant decrease in antioxidant enzymes were observed in
      untreated diabetic rats. Administration of D-limonene to diabetic rats for 45
      days caused a significant reduction in the levels of lipid peroxidation by
      products and an increase in the activities of antioxidant enzymes, when compared
      with the untreated diabetic group. There was no significant difference in normal
      treated groups, when compared with normal rats. Biochemical observations were
      substantiated with the help of histopathological examinations through its
      antioxidant properties and thereby conferred protection against STZ-induced
      diabetic rats. The result of this study indicates that D-limonene has antioxidant
      potential in addition to its antidiabetic effect in experimental diabetes.

PMID- 22998494
TI  - Histological evaluation at different times after augmentation of extraction sites
      grafted with a magnesium-enriched hydroxyapatite: double-blinded randomized
      controlled trial.
AB  - OBJECTIVES: To histologically analyze the early angiogenesis-osteogenesis
      interplay in post-extraction sockets augmented with magnesium-enriched
      hydroxyapatite (Mg-enriched HA). MATERIAL AND METHODS: Ten post-extraction sites
      underwent post-extraction ridge preservation procedure. According to
      randomization, sites were divided into two balanced groups and bone specimens
      were collected 2 or 4 months after surgery. Sections were stained with
      hematoxylin/eosin, Masson-Goldner trichrome, and tartrate-resistant acid
      phosphatase (TRAP), respectively. Furthermore, indirect immunohistochemistry was
      performed using alkaline phosphatase, CD34 and caveolin-1 antibodies. Mean values
      and standard deviations were calculated for each outcome variable. Data were then
      compared using one-way ANOVA test. P < 0.05 was considered statistically
      significant. RESULTS: Histomorphometric analysis presented 15.0% (+/-3.5)
      regenerated bone after 2 months of healing. After 4 months, regenerated bone
      increased 5.1-fold up to 77.4% (+/- 8.6) (P < 0.001). On the contrary, vessels
      and capillary reduced from 645 (+/-33) to 255 (+/- 94) (caveolin-1 expression, P
      = 0.008). These findings were confirmed by CD34 expression (301 +/- 95 and 88 (+/
      24), respectively, at 2 and 4 months (P = 0.046). CONCLUSIONS: Within the limits
      of the present randomized controlled study, it can be concluded that Mg-enriched
      HA is a suitable material for socket preservation and ensures early angiogenesis
      and early osteogenesis.

PMID- 22998495
TI  - Spinal cord injuries in young children: a review of children injured at 5 years
      of age and younger.
AB  - AIM: To determine the epidemiology and complications of spinal cord injuries
      (SCIs) in children injured at 5 years of age and younger who were seen between
      1981 and 2008 at a children's hospital in the USA. METHOD: Complications studied
      were scoliosis, hip dysplasia, latex allergies, autonomic dysreflexia, pressure
      ulcers, spasticity, deep venous thrombosis, and kidney stones. Demographic and
      injury-related factors included age at injury, etiology, level of injury,
      American Spinal Injury Association Impairment Scale (AIS), and SCIs without
      radiological abnormalities (SCIWORA). RESULTS: Of the 159 individuals seen (92
      males, 67 females) median age at injury was 2 years (range 0 y-5 y 11 mo). Forty
      nine percent were injured in vehicular accidents, 60% had complete injuries, 66%
      had paraplegia, and 72% had SCIWORA. Ninety-six percent developed scoliosis, 57%
      had hip dysplasia, and 7% had latex allergy. Thirty-four percent with injuries at
      or above T6 experienced autonomic dysreflexia, 41% developed pressure ulcers, and
      61% experienced spasticity. Of those without bowel or bladder control, 82% were
      on intermittent catheterization and 69% were on a bowel program. Median age of
      initiating wheelchair use was 3 years 4 months (range 1 y 2 mo-12 y 5 mo). Twenty
      four were community ambulators, and they were more likely to have AIS D lesions
      (half the key muscle functions below the level of injury have a muscle grade 3 or
      greater) and less likely to have skeletal complications. INTERPRETATION: The
      epidemiology, complications, and manifestations of SCIs in children injured at a
      young age are unique and differ distinctively from adolescent and adult-onset
      SCIs.

PMID- 22998496
TI  - Distinct variant of Sweet's syndrome: bortezomib-induced histiocytoid Sweet's
      syndrome in a patient with multiple myeloma.

PMID- 22998497
TI  - Down-modulation of expression, or dephosphorylation, of IG20/MADD in tumor
      necrosis factor-related apoptosis-inducing ligand-resistant thyroid cancer cells
      makes them susceptible to treatment with this ligand.
AB  - BACKGROUND: The IG20/MADD gene is overexpressed in thyroid cancer tissues and
      cell lines, and can contribute to tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) resistance. The ability of the MADD protein to resist
      TRAIL-induced apoptosis is dependent upon its phosphorylation by Akt.
      Interestingly, while TRAIL induces a significant reduction in the levels of
      phospho-Akt (pAkt) and phospho-MADD (pMADD) in TRAIL-sensitive cells, it fails to
      do so in TRAIL-resistant cells. In this study, we investigated if MADD
      phosphorylation by Akt was contributing to TRAIL resistance in thyroid cancer
      cells. METHODS: We determined the susceptibility of different thyroid cancer cell
      lines to TRAIL-induced apoptosis by fluorescence-activated cell sorting (FACS)
      analysis. We tested for various TRAIL resistance factors by FACS analyses or for
      IG20/MADD expression by quantitative reverse transcription-polymerase chain
      reaction. We determined the levels of pAkt and pMADD upon TRAIL treatment in
      thyroid cancer cells by Western blotting. We tested if down-modulation of
      IG20/MADD gene expression using shRNA or phosphorylation using a dominant
      negative Akt (DN-Akt) or pretreatment with LY294002, a PI3 kinase inhibitor,
      could help overcome TRAIL resistance. RESULT: BCPAP and TPC1 cells were
      susceptible, while KTC1 and FTC133 cells were resistant, to TRAIL-induced
      apoptosis. The differential susceptibility to TRAIL was not related to the levels
      of expression of death receptors, decoy receptors, or TRAIL. KTC1 and FTC133
      cells showed higher levels of IG20/MADD expression relative to BCPAP and TPC1,
      and were rendered susceptible to TRAIL treatment upon IG20/MADD knockdown.
      Interestingly, upon TRAIL treatment, the pAkt and pMADD levels were reduced in
      TRAIL-sensitive BCPAP and TPC1 cells, while they remained unchanged in the
      resistant KTC1 and FTC133 cells. While expression of a constitutively active Akt
      in BCPAP and TPC1 cells rendered them resistant to TRAIL, pretreating KTC1 and
      FTC133 cells with LY294002 rendered them TRAIL-sensitive. Moreover, expression of
      a DN-Akt in KTC1 and FTC133 cells reduced the levels of pAkt and pMADD and
      sensitized them to TRAIL-induced apoptosis. CONCLUSION: Our results show that
      pMADD is an important TRAIL resistance factor in certain thyroid cancer cells and
      suggest that down-modulation of either IG20/MADD expression or phosphorylation
      can render TRAIL-resistant thyroid cancer cells sensitive to TRAIL.

PMID- 22998498
TI  - Quality assessment of protein model-structures based on structural and functional
      similarities.
AB  - BACKGROUND: Experimental determination of protein 3D structures is expensive,
      time consuming and sometimes impossible. A gap between number of protein
      structures deposited in the World Wide Protein Data Bank and the number of
      sequenced proteins constantly broadens. Computational modeling is deemed to be
      one of the ways to deal with the problem. Although protein 3D structure
      prediction is a difficult task, many tools are available. These tools can model
      it from a sequence or partial structural information, e.g. contact maps.
      Consequently, biologists have the ability to generate automatically a putative 3D
      structure model of any protein. However, the main issue becomes evaluation of the
      model quality, which is one of the most important challenges of structural
      biology. RESULTS: GOBA--Gene Ontology-Based Assessment is a novel Protein Model
      Quality Assessment Program. It estimates the compatibility between a model
      structure and its expected function. GOBA is based on the assumption that a high
      quality model is expected to be structurally similar to proteins functionally
      similar to the prediction target. Whereas DALI is used to measure structure
      similarity, protein functional similarity is quantified using standardized and
      hierarchical description of proteins provided by Gene Ontology combined with
      Wang's algorithm for calculating semantic similarity. Two approaches are proposed
      to express the quality of protein model-structures. One is a single model quality
      assessment method, the other is its modification, which provides a relative
      measure of model quality. Exhaustive evaluation is performed on data sets of
      model-structures submitted to the CASP8 and CASP9 contests. CONCLUSIONS: The
      validation shows that the method is able to discriminate between good and bad
      model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean
      Pearson correlation to the observed quality of models in our CASP8 and CASP9
      based validation sets. GOBA also obtained the best result for two targets of
      CASP8, and one of CASP9, compared to the contest participants. Consequently, GOBA
      offers a novel single model quality assessment program that addresses the
      practical needs of biologists. In conjunction with other Model Quality Assessment
      Programs (MQAPs), it would prove useful for the evaluation of single protein
      models.

PMID- 22998499
TI  - Dielectric behaviors of typical benzene monosubstitutes, bromobenzene and
      benzonitrile.
AB  - The dielectric behaviors of typical benzene monosubstitutes, bromobenzene (Br-Bz)
      and benzonitrile (NC-Bz), were investigated up to 3 THz in the pure liquid state
      over a temperature range from 10 to 60  degrees C to understand differences in
      molecular motions of these simple, planar molecules bearing rather different
      electric dipole moments: 1.72 and 4.48 D for Br-Bz and NC-Bz in gaseous state,
      respectively. Temperature dependence of spin-lattice relaxation time (T(1)) for
      (13)C NMR and viscosities for these liquids were also determined to obtain
      information for molecular motions. Moreover, depolarized Rayleigh scattering
      (DRS) experiments were carried out for both liquids at 20  degrees C to determine
      frequency dependencies of optical susceptibilities up to 8 THz directly relating
      to rotational motions of their molecular planes. Most Br-Bz molecules rotate
      freely over a temperature range examined, showing a Kirkwood correlation factor
      close to g(K) ~ 1.0 at dielectric Debye-type relaxation times (ca. 18 ps at 20 
      degrees C) essentially identical to microscopic (dielectric) relaxation times
      evaluated from T(1)(13)C NMR data. A small amount of Br-Bz molecules forms
      dimeric intermolecular associations in an antiparallel configuration of dipole
      moments. On the other hand, NC-Bz molecules form stable dimers in the
      antiparallel dipole configuration at a population much higher than that of Br-Bz
      because of a markedly greater dipole moment than that of Br-Bz. A major
      dielectric relaxation mechanism for NC-Bz found at ca. 70 ps at 20  degrees C
      results from the dissociation process of dimers with a lifetime longer than a
      rotational relaxation time, observable as a minor dielectric relaxation mechanism
      at ca. 12 ps at 20  degrees C, of individual monomeric NC-Bz molecules without
      the formation of dimers. The formation of stable dimers in an antiparallel
      configuration is responsible for the observed small g(K) values, ca. 0.5, and
      disagreement between major (or minor) dielectric relaxation times and microscopic
      dielectric relaxation times over the entire temperature range examined.

PMID- 22998500
TI  - Clinical effects of buttonhole cannulation method on hemodialysis patients.
AB  - Although the buttonhole cannulation method is now widely used as an alternative
      to the rope-ladder method in most countries, only the latter method is used in
      Korea. This study was performed to investigate clinical benefit of the buttonhole
      technique for arteriovenous fistula (AVF) cannulation in maintenance hemodialysis
      (HD) patients. Thirty-two patients receiving HD via mature AVF were included and
      AVF cannulation was performed by 20 experienced nurses. During the 8 weeks, AVFs
      were cannulated by the rope-ladder method with 15-gauge sharp needles. After
      creating of 2 pairs of tunnel tracks by sharp needles for 7 weeks, AVFs were
      cannulated by the buttonhole method using 15-gauge blunt needles during the 16
      weeks. Vascular access blood flow rate (BFR), dialysis venous pressure (DVP), and
      dialysis adequacy (Kt/V) were measured within the first week of the two
      cannulation methods. Cannulation pain, hemostasis time, and nurse's stress were
      evaluated at the end of the two methods. There were no statistical differences in
      vascular access BFR (P = 0.139), DVP (P = 0.152), and dialysis adequacy (P =
      0.343) between the two methods. However, the buttonhole method shortened
      hemostasis time (P = 0.001) and decreased cannulation pain (P = 0.001) as well as
      nurse's stress (P = 0.001) compared with the rope-ladder method. In conclusion,
      the buttonhole cannulation method improves hemostasis time, cannulation pain, and
      nurse's stress without a change in vascular access BFR and dialysis adequacy in
      HD patients.

PMID- 22998501
TI  - Blue cone monochromatism in a female due to skewed X-inactivation.
AB  - Blue cone monochromatism (BCM) is a rare cone dystrophy with recessive X-linked
      inheritance and therefore diagnosed in males whereas females are clinically
      unaffected. We present a female with clinically manifested BCM. The diagnosis was
      genetically verified with the identification of one single red-green OPN1LW/MW
      hybrid gene harboring a point mutation c.607C>G, p.Cys203Arg that associates with
      BCM and in addition a completely biased X-inactivation in DNA isolated from full
      blood and buccal mucosa. The present case illustrates that females may develop
      symptoms of recessive X-linked eye diseases in rare cases.

PMID- 22998502
TI  - Confirmation of the association between the TCF4 risk allele and Fuchs
      endothelial corneal dystrophy in patients from the Midwestern United States.
AB  - PURPOSE: To determine the role of the single nucleotide polymorphism (SNP)
      (rs613872) in the TCF4 gene in Fuchs endothelial corneal dystrophy (FECD) in
      patients from Iowa. METHODS: A cohort of 82 patients with FECD and 163 normal
      control subjects from Iowa were genotyped at the SNP rs613872 using a real-time
      allelic discrimination assay. RESULTS: The frequencies of the alleles of rs613872
      were compared between FECD patients and control subjects. A highly significant
      association (p-value = 2.96 * 10(-10)) was detected between this SNP and FECD.
      Comparison of the genotypes of SNP rs613872 between FECD patients and control
      subjects produced a p-value of 2.43 * 10(-10). CONCLUSION: Prior reports have
      shown that SNP rs613872 in the TCF4 gene is highly associated with FECD. Our
      study confirms this association and shows that the TCF4 gene has an important
      role in the pathogenesis of corneal disease in patients from Iowa.

PMID- 22998503
TI  - In vivo virus-based macrofluorogenic probes target azide-labeled surface glycans
      in MCF-7 breast cancer cells.
AB  - Chemical addressability of viral particles has played a pivotal role in adapting
      these biogenic macromolecules for various applications ranging from medicine to
      inorganic catalysis. Cowpea mosaic virus possesses multiple features that are
      advantageous for the next generation of virus-based nanotechnology: consistent
      multimeric assemblies dictated by its genetic code, facile large scale
      production, and lack of observable toxicity in humans. Herein, the chemistry of
      the viral particles is extended with the use of Cu-free strain-promoted azide
      alkyne cycloaddition reaction, or SPAAC reaction. The elimination of Cu, its
      cocatalyst and reducing agent, simplifies the reaction scheme to a more
      straightforward approach, which can be directly applied to living systems. As a
      proof of concept, the viral particles modified with the azadibenzylcyclooctyne
      functional groups are utilized to trigger and amplify a weak fluorescent signal
      (azidocoumarin) in live cell cultures to visualize the non-natural sugars. Future
      adaptations of this platform may be developed to enhance biosensing applications.

PMID- 22998504
TI  - Deprivation and ethnicity impact on diabetes control and use of treatment
      regimen.
AB  - AIMS: Deprivation and/or ethnicity impact on care delivery. We have assessed how
      these factors influence diabetes care in a paediatric clinic. METHODS: We related
      access to care [type of insulin treatment regimen-twice daily, multiple daily
      injections and insulin pump therapy (continuous subcutaneous insulin infusion)],
      measures of care process (HbA(1c)) and an approximate measure of satisfaction
      with the service (clinic attendance rate) in 325 (170 male) children and young
      people with Type 1 diabetes (mean age 10.6 years, mean duration of diabetes of
      4.5 years), with indices of deprivation and ethnicity. RESULTS: Of the 325
      children and young people, 2.7% received twice-daily insulin, 48.4% multiple
      daily injections and 48.9% continuous subcutaneous insulin infusion. Median
      clinic HbA(1c) was 62 mmol/mol (7.8%) and those receiving the insulin pump
      therapy had the lowest HbA(1c). Four ethnic groups were represented; White
      British 81.6%, Asian non-Indian 6.5%, African 8.1% and Asian Indian 3.8%. Mean
      deprivation score was 21.06. White British and Asian Indian groups were more
      likely to receive insulin pump therapy (chi(2) = 50.3; P < 0.001). Attendance
      rates were 94.1% and did not differ across ethnic groups. Deprivation was related
      to ethnicity and HbA(1c) (R(2) = 0.02; P = 0.02). There was no relationship
      between clinic attendance and deprivation. Insulin regimen and ethnicity were
      associated with HbA(1c) (R(2) = 0.096; P < 0.001). Similar findings were obtained
      when analysis was confined to the White British population. CONCLUSIONS: These
      data suggest that deprivation and ethnicity influence diabetes control and how
      intensive insulin therapy is utilized. A better consideration of the needs of
      different ethnic groups is required to ensure equitable care delivery in
      paediatric diabetes.

PMID- 22998505
TI  - Bacteria and diatom co-occurrence patterns in microbial mats from polar desert
      streams.
AB  - The ephemeral stream habitats of the McMurdo Dry Valleys of Antarctica support
      desiccation and freeze-tolerant microbial mats that are hot spots of primary
      productivity in an otherwise inhospitable environment. The ecological processes
      that structure bacterial communities in this harsh environment are not known;
      however, insights from diatom community ecology may prove to be informative. We
      examined the relationships between diatoms and bacteria at the community and
      taxon levels. The diversity and community structure of stream microbial mats were
      characterized using high-throughput pyrosequencing for bacteria and morphological
      identification for diatoms. We found significant relationships between diatom
      communities and the communities of cyanobacteria and heterotrophic bacteria, and
      co-occurrence analysis identified numerous correlations between the relative
      abundances of individual diatom and bacterial taxa, which may result from species
      interactions. Additionally, the strength of correlations between heterotrophic
      bacteria and diatoms varied along a hydrologic gradient, indicating that flow
      regime may influence the overall community structure. Phylogenetic consistency in
      the co-occurrence patterns suggests that the associations are ecologically
      relevant. Despite these community- and taxon-level relationships, diatom and
      bacterial alpha diversity were inversely correlated, which may highlight a
      fundamental difference between the processes that influence bacterial and diatom
      community assembly in these streams. Our results therefore demonstrate that the
      relationships between diatoms and bacteria are complex and may result from
      species interactions as well as niche-specific processes.

PMID- 22998506
TI  - Tularemia during pregnancy: report of four cases.
AB  - Tularemia during pregnancy is exceedingly rare and has been reported infrequently
      in Europe. A review of the literature identified only 3 documented cases. Herein
      we report 4 tularemia cases occurring early in the second and third trimesters,
      which were successfully managed without any adverse pregnancy outcomes.

PMID- 22998507
TI  - Experimental verification of the homoaromaticity of 1,3,5-cycloheptatriene and
      evaluation of the aromaticity of tropone and the tropylium cation by use of the
      dimethyldihydropyrene probe.
AB  - By use of a dimethyldihydropyrene experimental probe for aromaticity, 1,3,5
      cycloheptatriene (16) is demonstrated to be a neutral homoaromatic hydrocarbon!
      On the basis of (1)H NMR results, 16 is judged to be ~30%, tropone 18 ~20%, and
      tropylium 22 ~50% as aromatic as benzene. The latter result may be an
      underestimation because of charge delocalization. The B3LYP/6-31G* calculated
      geometries and GIAO-HF/6-31G*//B3LYP/6-31G* calculated NMR chemical shifts and
      nucleus-independent chemical shifts (NICS) support these conclusions. These
      estimates were obtained by synthesis of the annelated dihydropyrenes 7 (tropone
      fused), 9 (1,3,5-cycloheptatriene fused), and 10 (tropylium fused). [4 + 3]
      Cycloaddition of the isofuran 5 with an oxyallyl cation (prepared from 2,4
      dibromopentan-3-one) gave the C7 fused dihydropyrene 6 in 77% yield. Elimination
      of water gave tropone 7 in 61% yield, which, via LiAlH(4) reduction to alcohol 8
      (48% yield) and treatment with HBF(4), gave quantitatively tropylium cation 10.
      When ketone 7 was reduced with AlH(3) (generated from AlCl(3)/LiAlH(4)) in
      ether/benzene at 25  degrees C, the isomeric cycloheptatrienes 11 (70% yield) and
      9 (15% yield) were obtained.

PMID- 22998508
TI  - Renal function-dependent association of serum uric acid with metabolic syndrome
      and hepatic fat content in a middle-aged and elderly Chinese population.
AB  - The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly
      dependent on its physicochemical properties, and hyperuricaemia associated with
      different conditions may have different clinical meanings. The aim of the present
      study was to investigate the association of serum UA levels with metabolic
      syndrome and non-alcoholic fatty liver disease (NAFLD) in a middle-aged and
      elderly population with normal and impaired renal function. The cross-sectional
      study was performed on 1141 participants (426 men, 715 women; mean age 62 years)
      enrolled from the Shanghai Changfeng community. Each participant underwent a
      standard interview, with anthropometric and laboratory measurements. Hepatic fat
      content (HFC) was determined by a newly established quantitative ultrasound
      method. Univariate correlation analysis showed that serum UA was associated with
      all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially
      in participants with a normal estimated glomerular filtration rate (eGFR; r =
      0.255, P < 0.001). Logistic regression analysis demonstrated an independent
      association of serum UA with metabolic syndrome and NAFLD in participants with
      normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m(2) .
      Furthermore, multivariate linear analysis showed that UA levels were
      independently associated with HFC (P = 0.003), but only in participants with
      normal eGFR. Elevated serum UA is independently associated with metabolic
      syndrome and NAFLD in patients with normal renal excretory function. However, in
      those with renal insufficiency, hyperuricaemia has no association with metabolic
      disorders.

PMID- 22998509
TI  - Novel aldose reductase inhibitors: a patent survey (2006--present).
AB  - INTRODUCTION: Initially studied for its central role in the pathogenesis of
      chronic diabetic complications, aldose reductase (ALR2) gains more attention over
      the years as its implication in inflammatory diseases is being established, along
      with the therapeutic potential of its inhibitors. AREAS COVERED: Reviewing the
      patents that were published since 2006, it is getting clear that the search for
      new chemical entities has subsided, giving rise to natural products and plant
      extracts with ALR2 inhibitory activity. Other aspects that were prominent were
      the search for proper forms of known inhibitors, in a way to improve their
      impaired physicochemical profile, as well as potential combination therapies with
      other compounds of pharmaceutical interest. On the spotlight were patents
      enhancing the therapeutic usage of aldose reductase inhibitors (ARIs) to various
      pathological conditions including cancer and inflammation-mediated diseases such
      as sepsis, asthma, and cancer. EXPERT OPINION: Although new chemical entities are
      scarcely registered and patented after many years of inconclusive clinical
      trials, the involvement of ALR2 to inflammatory pathologies might renew the
      interest in the field of ARIs.

PMID- 22998510
TI  - Sensory interventions for children: where does our profession stand?

PMID- 22998512
TI  - Inter-rater reliability of three adult handwriting legibility instruments.
AB  - BACKGROUND/AIM: Legibility is important for functional, handwritten
      communication. Deficits in legibility can impair occupational performance
      following stroke or trauma. Few instruments are available to assess adult
      handwriting legibility during rehabilitation. The aim of this study was to
      compare inter-rater reliability of a new four-point legibility rating instrument
      with two existing instruments, and describe scale structure and item difficulty
      of each instrument. METHODS: Three trained raters scored 60 handwriting samples
      using: (i) a Four-Point Scale (FPS); (ii) the modified Evaluation Tool of
      Children's Handwriting (mETCH); and (iii) the new modified FPS. Rater concordance
      and exact agreement were investigated using the intra-class correlation
      coefficient (ICC(3,1) ), multi-rater kappa (kappa) and Krippendorff's alpha
      (alpha). Cronbach's alpha was calculated to examine internal consistency
      reliability, and Rasch modelling was used to examine scale structure and item
      difficulty. RESULTS: Rater concordance for the FPS was fair (ICC(3,1)  = 0.37);
      exact agreement was poor (kappa = 0.19; alpha = 0.19). Rater concordance for the
      two mETCH subtests was fair to moderate (ICC(3,1)  = 0.39-0.50), but with no
      exact agreement (kappa < 0.00). Rater concordance for three subtests of the
      modified FPS was slight to moderate (ICC(3,1)  = 0.16-0.51); exact agreement
      ranged from nil to fair (kappa = -0.06-0.30; alpha = -0.05-0.30). Rasch modelling
      confirmed internal consistency of instruments, but was low between-rater
      consistency (rater severity variability). CONCLUSIONS: A reliable instrument for
      measuring change over time remains elusive. In the meantime, these instruments
      can be used by individual clinicians to diagnose and rate legibility.

PMID- 22998511
TI  - Children who experience difficulties with learning: mother and child perceptions
      of social competence.
AB  - There is an emphasis on the social competence of children who have difficulties
      with learning as a significant percentage also experience reduced social skills.
      Social competence in the classroom is becoming increasingly important as the
      school curriculum incorporates group work and socially directed activities for
      purposes of learning. A goal of occupational therapy for children with learning
      difficulties and their parents is that they 'fit' into their social group and
      form friendships. While teachers are able to identify social skills that are
      required for life at school, less is known about how children perceive their
      interactions. This study aimed to explore social interaction during occupational
      performance at school and at home from the perception of children with learning
      difficulties and their mothers. Participants included 10, 8- to 12-year-old
      children who had difficulties with learning and their 10 mothers. Children were
      interviewed using semi-structured focus groups. Mothers participated in semi
      structured interviews. Four main themes emerged from this study, including the
      importance of social skills, effects of poor social skills, difficulties with
      planning and problem solving in social situations and impact of social competence
      on a child's occupational performance. The study revealed that social
      participation is perceived to be an integral part of the child's ability to
      participate in occupational performance, and that children have definite
      perspectives on the importance of social competence. Children in this study
      indicated that their social skills were adequate when in an one-to-one situation
      but not in a group.

PMID- 22998513
TI  - Clinical reasoning process underlying choice of teaching strategies: a framework
      to improve occupational therapists' transfer skill interventions.
AB  - BACKGROUND/AIM: Clinical reasoning, a critical skill influenced by education and
      practice context, determines how occupational therapists teach transfer skills.
      Teaching strategies affect intervention efficacy. Although knowledge about the
      way teaching strategies are chosen could help improve interventions, few studies
      have considered this aspect. Therefore, the aim of this study was to explore the
      clinical reasoning process of occupational therapists underlying the choice of
      strategies to teach older adults transfer skills. METHODS: A grounded theory
      study was carried out with eleven community occupational therapists recruited in
      six Health and Social Services Centres in Quebec, Canada. Data were collected
      through observations of teaching situations (n = 31), in-depth semi-structured
      interviews (n = 12) and memos, and were analysed using constant comparative
      methods. Memos were also used to raise codes to conceptual categories, leading to
      an integrative framework. Rigour was assured by following scientific criteria for
      qualitative studies. RESULTS: The integrative framework includes the clinical
      reasoning process, consisting of eight stages, and its factors of influence.
      These factors are internal (experiences and elements of personal context) and
      external (type of transfer, clients' and their environment's characteristics and
      practice context). CONCLUSIONS: The clinical reasoning process underlying the
      choice of strategies to teach transfer skills was conceptualised into an
      integrative framework. Such a framework supports clinicians' reflective practice,
      highlights the importance of theory and practice of pedagogy in occupational
      therapists' education, and encourages consideration and better documentation of
      the possible influence of practice context on teaching interventions. As such,
      this integrative framework could improve occupational therapists' transfer skill
      interventions with older adults.

PMID- 22998514
TI  - Occupational therapy students' perceptions of occupational therapy.
AB  - BACKGROUND/AIMS: An understanding of students' perceptions of occupational
      therapy on entry is required to recognise how professional socialisation occurs
      through curriculum. Findings pertain to a qualitative study investigating
      students' perceptions of occupational therapy upon entry to two occupational
      therapy programmes in Australia. METHODS: Students commencing Bachelor of
      Occupational Therapy and Masters of Occupational Therapy Studies programmes
      participated in the study (n = 462). A purpose-designed questionnaire was
      distributed to students in the first lecture of each programme. Preliminary
      analysis comprised identification of keywords/phrases and coding categories were
      generated from patterns of keywords. Frequency counts and percentages of
      keywords/phrases within categories were completed. RESULTS: Students' responses
      were categorised as 'what' occupational therapists do; 'how' they do it; 'why'
      they do it; and 'who' they work with. In 'what' occupational therapists do
      students frequently described 'helping' people. Both undergraduate and graduate
      entry masters students used the term 'rehabilitation' to describe how
      occupational therapy is done, with graduate entry students occasionally
      responding with 'through occupation' and 'modifying the environment'. Students
      perceived the 'why' of occupational therapy as getting back to 'everyday
      activities', with some students emphasising returning to 'normal' activities or
      life. Regarding the 'who' category, students also thought occupational therapists
      worked with people with an 'injury' or 'disability'. CONCLUSIONS: Students
      entered their occupational therapy programmes with perceptions consistent with
      the general public's views of occupational therapy. However, graduate entry
      students exposed to a pre-reading package prior to entry had more advanced
      occupational therapy concepts than undergraduate students.

PMID- 22998515
TI  - Community mobility in the context of universal design: inter-professional
      collaboration and education.
AB  - BACKGROUND/AIM: The design of built environments is a critical factor in
      facilitating participation for all community members. This study aimed to explore
      key stakeholders' views on the role and collaboration of occupational therapists
      and architects in relation to universal design and the built environment. This
      study is currently the only research to focus on the needs and practices of both
      occupational therapy and architecture in universal design. The results have
      implications for both clinical practice and professional education, and highlight
      an area of developing interest in occupational therapy. METHODS: Focus groups and
      semi-structured telephone interviews were conducted with key stakeholders
      involved in the design of built environments. Data from these interviews were
      analysed qualitatively, using codes of interpreted meaning which were then
      organised into themes. RESULTS: Three main themes emerged in relation to inter
      professional collaboration around universal design: 'form vs. function', 'the
      earlier the better' and 'universal design as a specialist area'.
      DISCUSSION/CONCLUSIONS: Although there are areas of synergy between occupational
      therapy and architecture in universal design, each profession has its own
      strengths and skills to bring to the design process. Given the multidisciplinary
      nature of ensuring designs support participation in occupations and roles, both
      professions could benefit from opportunities to meaningfully collaborate during
      professional education and in the workplace.

PMID- 22998516
TI  - Time use, role participation and life satisfaction of older people: impact of
      driving status.
AB  - BACKGROUND/AIM: Driving cessation has been recognised as affecting the health and
      wellbeing of older people. Further exploration of the impact of driving status on
      time use, role participation and life satisfaction was required. METHODS: A cross
      sectional survey of 234 older people (current drivers, retired drivers and people
      who have never driven) was employed. Time use in the previous week, role
      participation and life satisfaction were measured and compared between the
      groups, while controlling for sociodemographic variables (health status,
      activities of daily living and instrumental activities of daily living status,
      gender, age and living situation). RESULTS: When compared to current drivers,
      retired drivers had significantly lower life satisfaction (P = 0.01), fewer
      present roles (P < 0.0001) and were less likely to participate in volunteer (P =
      0.005) and family member roles (P = 0.009). Retired drivers spent less time on
      social leisure (P = 0.002) and away from home (P = 0.0001), and more time in
      solitary leisure (P= 0.0001). Comparing the participation of retired drivers with
      those who had never driven indicated that retired drivers spent significantly
      less time in volunteer work (P = 0.009). CONCLUSIONS: The findings indicate that
      older non-drivers may require support for participation and wellbeing.

PMID- 22998517
TI  - The potential of occupational therapy services for students with disabilities
      within tertiary education settings.

PMID- 22998518
TI  - Group cognitive-behavioural therapy aimed at self-management reduced fatigue
      impact in people with rheumatoid arthritis is better than fatigue information
      alone.

PMID- 22998519
TI  - Cognitive stimulation groups may produce small, short-term improvement in
      cognition in adults with mild-to-moderate dementia.

PMID- 22998521
TI  - Halide ordering in reduced mixed halides, chlorides/iodides, of zirconium:
      syntheses and structures of Cs2[(Zr6B)(Cl,I)15] cluster compounds.
AB  - A series of high-temperature solid state chemical reactions was carried out in
      the quasi-quarternary mixed-halide Cs-Zr-B-(Cl,I) system with stoichiometries
      aiming for zirconium cluster phases of the Cs(2)[(Zr(6)B)X(15)] type (X = mixture
      of Cl + I). In the phase range from ~ Cs(2)[(Zr(6)B)Cl(13)I(2)] to
      Cs(2)[(Zr(6)B)Cl(3)I(12)] the structures of the obtained cluster phases are
      derived from the orthorhombic CsK[(Zr(6)B)Cl(15)]. At a composition of
      Cs(2)[(Zr(6)B)Cl(~10) I(~4)] a lower symmetry, monoclinic derivative has been
      found. X-ray diffraction data of single crystals of three compounds of this phase
      system were collected, orthorhombic Cs(2)[(Zr(6)B)Cl(12.99(3))I(2.01)] (1),
      (Pmma, Z = 4, a = 19.304(4), b = 14.617(3), c = 9.921(2) A, R1/wR2 =
      0.0444/0.0886), monoclinic Cs(2)[(Zr(6)B)Cl(10.63(3))I(4.37)] (2), (P2/c, Z = 4,
      a = 14.9502(3), b = 10.0098(2), c = 19.8798(4) A, beta = 90.977(1) R1/wR2 =
      0.0460/0.1182), and orthorhombic Cs(2)[(Zr(6)B)Cl(8.79(4))I(6.21)] (3) (Pmma, Z =
      4, a = 20.0534(4), b = 15.1488(3), c = 10.1739(2) A, R1/wR2 = 0.0494/0.1123).
      These compounds are obtained as single phase products. As in other known mixed
      halide systems halide ordering is observed, such that the different halide sites
      have different amounts of Cl and I. With increasing amount of iodide, relative to
      Cl, the cluster-interconnecting halide sites are more and more occupied by I. For
      the first time it is observed for 3 that a halide site, which forms a linear
      bridge between two neighboring Zr(6)B cluster units (so far known examples are
      solely occupied by Cl), is statistically mixed occupied by Cl and I.
      Nevertheless, both halide types achieve acceptable bonding situations (bond
      lengths) because the I atoms are moved out of the linearly bridging position,
      thereby achieving longer Zr-X distances than the Cl atom, which remains linearly
      bridging. The generally interesting aspect of this paper is that in the very
      complex systems the atoms of the mixed occupied sites as well as those of the
      cation sites arrange with respect to the atomic environment, such that all of
      them have optimized bonding situations.

PMID- 22998522
TI  - Preclinical models for pediatric solid tumor drug discovery: current trends,
      challenges and the scopes for improvement.
AB  - INTRODUCTION: The enhancement in pediatric cancer survival achieved in the past
      few decades has been confined to low- and moderate-risk cancers, whereas no
      notable improvement in survival was observed in high-risk and advanced-stage
      childhood cancers. High attrition rate of candidate drugs in clinical trials is a
      major hurdle in the development of effective therapies for pediatric solid
      tumors. In order to reduce the failure rate of candidate drugs in clinical
      trials, more effective strategies are needed to enhance the predictability of
      preclinical testing. AREAS COVERED: The authors have described the current trends
      in preclinical drug development for treating pediatric solid tumors. Furthermore,
      the authors review their limitations and the available remedies, with regards to
      choice of models, pharmacokinetic considerations and the criteria for assessing
      the long-term efficacy of a candidate drug. EXPERT OPINION: In many solid tumors,
      common differences between pediatric and adult cancers have been observed, and
      therefore, clinical trials for pediatric solid tumors must be conducted on the
      basis of preclinical observations in pediatric solid tumor models. There is a
      need to invest in extensive preclinical testing on pediatric solid tumor models.
      None of the preclinical models can fully recapitulate the human cancers.
      Therefore, these limitations must be considered while conducting a preclinical
      trial. The dose and schedule of drugs used for preclinical testing must be
      clinically relevant. While testing the efficacy of drugs, the markers of
      apoptosis, drug resistance, hypoxia and tumor-initiating cells can inform us
      about the long-term therapeutic response of a cancer.

PMID- 22998523
TI  - How to deal with laryngeal amyloidosis? Experience based on 16 cases.
AB  - INTRODUCTION: Amyloidosis is characterized by the deposition of amorphous
      fibrillar protein (amyloid) in the intercellular or intracellular space.
      Localized amyloidosis is rare in the head and neck area. In Polish literature of
      the last decade it has been the subject of case studies. AIM: The goal of the
      study was to carry out a retrospective analysis of patients treated for
      amyloidosis in the Department of Otolaryngology and Head and Neck Surgery of the
      Poznan University of Medical Sciences in the period from 2000 to 2009. Based on
      the collected clinical material, the authors made an attempt to determine the
      most frequent anatomical location of amyloid deposits and the most frequently
      affected organs, the type and duration of symptoms, the therapeutic approach,
      further diagnostic measures taken and the final outcome of the treatment. The
      next goal was to assess the number of microlaryngoscopies performed in patients
      with amyloidosis affecting the larynx as compared to the overall number of such
      procedures. MATERIAL: The detailed analysis included 16 patients with laryngeal
      amyloidosis. RESULTS: Amyloidosis of the larynx was found in only 0.52% of
      patients undergoing microlaryngoscopies in the period from 2000 to 2009. In the
      vast majority of patients (11 of 16), there was no suspicion of amyloidosis in
      the initial diagnosis. Only the histopathological assessment definitely confirmed
      the nature of pathological changes in the larynx. Glottis was the most common
      location of amyloid deposits in the study group. In all cases, additional studies
      and long-term monitoring of the postoperative course excluded generalized
      amyloidosis. CONCLUSIONS: Laryngeal amyloidosis is very rare, however it should
      be considered in the differential diagnosis in patients with laryngeal
      dysfunction. Surgery remains the treatment of choice in most patients, although
      the attempts of radiotherapy are undertaken. Preserving the normal function of
      the organ remains the priority.

PMID- 22998520
TI  - Intraclass correlation coefficients in the Brazilian Network for Surveillance of
      Severe Maternal Morbidity study.
AB  - BACKGROUND: The purpose of the study was to evaluate intraclass correlation
      coefficients (ICC) of variables concerning personal characteristics, structure,
      outcome and process in the Brazilian Network for Surveillance of Severe Maternal
      Morbidity study conducted to identify severe maternal morbidity/near miss cases
      using the World Health Organization criteria. METHOD: It was a cross-sectional,
      multicenter study involving 27 hospitals providing care for pregnant women in
      Brazil. Cluster size and the mean size of the primary sampling unit were
      described. Estimated prevalence rates, ICC, their respective 95% confidence
      intervals, the design effect and the mean cluster size were presented for each
      variable. RESULTS: Overall, 9,555 cases of severe maternal morbidity (woman
      admitted with potentially life-threatening conditions, near miss events or death)
      were included in the study. ICC ranged from < 0.001 to 0.508, with a median of
      0.035. ICC was < 0.1 for approximately 75% of the variables. For process-related
      variables, median ICC was 0.09, with 0.021 for those related to outcome. These
      findings confirm data from previous studies. Homogeneity may be considered minor,
      thus increasing reliability of these findings. CONCLUSIONS: These results may be
      used to design new cluster trials in maternal and perinatal health and to help
      calculate sample sizes.

PMID- 22998524
TI  - Up-regulated GLT-1 resists glutamate toxicity and attenuates glutamate-induced
      calcium loading in cultured neurocytes.
AB  - Glutamate transporter-1 (GLT-1) plays a dual role in glutamate transportation:
      both normally devotion to the clearance of glutamate and during some pathological
      conditions extruding glutamate to the extracellular space. Therefore, it is
      uncertain whether increased expression of GLT-1 will actually be helpful against
      glutamate excitotoxicity. In this study, GLT-1 up-regulation was induced by
      ceftriaxone, and L-glutamate was added to induce glutamate toxicity in primary
      cultured rat cortical cells. The results showed that up-regulated GLT-1 induced
      by 1 MUM ceftriaxone for 2 days markedly increased cell viability, decreased
      apoptotic cell death and alleviated ultrastructural damage induced by 50 MUM
      glutamate 15 min. as well as promoted L-[(3) H]-glutamate uptake in cultured
      cells. GLT-1 up-regulation had no effect on the intracellular free calcium
      concentration ([Ca(2+) ](i) ) in the resting situation, while relieved
      intracellular calcium overloading by reducing the elevation and promoting the
      recovery of [Ca(2+) ](i)  following stimulation of 50 MUM glutamate for 2 min.
      Applying 100 MUM dihydrokainic acid (GLT-1 antagonist) 30 sec. before glutamate
      eliminated the above effect of GLT-1 up-regulation on [Ca(2+) ](i) . In
      conclusion, GLT-1 up-regulation induced by ceftriaxone plays a positive glutamate
      transporting role against glutamate toxicity in primary cultured rat cortical
      cells.

PMID- 22998526
TI  - The influence of birth date and place of development on youth sport
      participation.
AB  - Previous research highlights the critical role that contextual factors play in
      shaping athlete development. The purpose of the present study was to investigate
      two of these contextual factors: birth date (known as the relative age effect,
      RAE) and city of development as determinants of participation in a sample of
      youth ice hockey players. The sample included 146,424 athletes registered with
      Ontario youth ice hockey between the 2004 and 2010 seasons. Chi-square statistics
      determined a significant RAE in youth ice hockey. Findings also revealed a
      significant association between small cities of development and increased youth
      ice hockey participation. Finally, there was no evidence of an interaction
      between relative age and city of development. The characteristics of smaller
      communities that may facilitate sport participation across all youth are
      discussed, along with recommendations for future research.

PMID- 22998525
TI  - The effect of pediatric traumatic brain injury on behavioral outcomes: a
      systematic review.
AB  - AIM: To review systematically the empirical evidence on traumatic brain injury
      (TBI) during childhood and subsequent behavioral problems. METHOD: An initial
      literature search with keywords 'brain injury,''children,' and 'behavior' was
      conducted using Web of Knowledge and PubMed databases. Ancestry was also used.
      Original research studies published between 1990 and February 2012 focusing on
      behavioral outcomes of children sustaining TBI from ages 0 to 18 years were
      included. RESULTS: Fifty studies, varying considerably in methodologies, were
      included in the review. Findings showed that up to 50% of brain-injured children
      are at risk for presenting with specific behavioral problems and disorders. These
      problems may emerge shortly or several years after injury and often persist and
      even worsen with time. These behavioral impairments appear to be moderated by the
      family environment. INTERPRETATION: Survivors of childhood TBI are at risk for
      developing and sustaining behavioral impairments. Stronger research is needed to
      identify cognitive and environmental factors that contribute to the onset and
      maintenance of these problems. Healthcare providers should ensure adequate follow
      up and assessment of a child's behavioral, social, and neurocognitive domains.
      Caregivers should be encouraged to provide positive environments and parenting
      styles, which may help reduce chronic behavioral problems after brain injury.

PMID- 22998527
TI  - Human lipoxygenase: developments in its structure, function, relevance to
      diseases and challenges in drug development.
AB  - Human lipoxygenases (LOXs) are the enzymes participating in the metabolism of the
      polyunsaturated fatty acids and catalyzing their oxidation to a variety of
      eicosanoids, which as the secondary signal transducers have a major impact on
      human homeostasis. They are involved in many diseases such as inflammatory
      responses, cancers, cardiovascular and kidney diseases, neurodegenerative
      disorders and metabolic syndrome. This review summarizes recent developments
      concerning human 12S-LOX and rabbit 15-LOX projected upon available structural
      data of LOX and COX oxidoreductases, with conclusions that might apply to LOX
      family of enzymes in general. Namely: (i) Human lipoxygenases might act as
      oligomers consisting of active and apo monomers. (ii) Sequential homodimers might
      act as structural heterodimers with the dimeric interface formed by the
      interactions resembling the leucine zipper in the coiled-coil superstructure.
      (iii) Two commonly recognized domains are not sufficient to explain LOX
      flexibility. Molecular architecture should contain assignment of another
      regulatory domain of alpha-beta character, possibly important in molecular
      signaling, which might provide another avenue for targeted drug development. (iv)
      Allosteric mechanism might involve orchestrated conformational changes and
      flexibility of the coils connecting the structured elements and ligands binding
      in more than one monomer.

PMID- 22998528
TI  - Chemistry and pharmacology of imexon and related cyanoaziridines.
AB  - Following the demonstration that addition of a 2-cyano group to aziridines
      prevented DNA alkylation and thus reduced toxicity, many novel 2-cyanoaziridines
      were synthesized and evaluated as immunomodulating and antitumor agents. They
      typically reacted with thiols such as cysteine, depleting them and allowing the
      accumulation of reactive oxygen species. Two of these compounds, azimexon and
      ciamexon, showed activity against tumors in clinical trials. Imexon was produced
      by cyclization of 2-cyanoaziridine-1- carboxamide in the presence of hydroxide
      ions. The two enantiomers were prepared by a process involving chiral
      chromatography. They were equipotent against cultured tumor cells. Imexon also
      reacts with thiols and it is especially potent against multiple myeloma in cell
      cultures. An efficient chemical synthesis and a lyophilization formulation of
      imexon as a water soluble, injectible drug, were developed. In Phase I and I/II
      clinical trials imexon showed hints of activity against a variety of tumors, but
      a randomized double-blind Phase II trial of imexon plus gemcitabine versus
      gemcitabine alone in pancreatic cancer showed no enhancement of activity above
      that of gemcitabine alone. This result was disappointing because in cell culture
      and mice the two compounds were synergistic. Based on a complete response in a
      Phase I trial, a new Phase II clinical trial of imexon is underway in non
      Hodgkins lymphoma.

PMID- 22998529
TI  - Higher risk of reoperation for bipolar and uncemented hemiarthroplasty.
AB  - BACKGROUND AND PURPOSE: Hemiarthroplasty as treatment for femoral neck fractures
      has increased markedly in Sweden during the last decade. In this prospective
      observational study, we wanted to identify risk factors for reoperation in
      modular hemiarthroplasties and to evaluate mortality in this patient group.
      PATIENTS AND METHODS: We assessed 23,509 procedures from the Swedish Hip
      Arthroplasty Register using the most common surgical approaches with modular uni-
      or bipolar hemiarthroplasties related to fractures in the period 2005-2010.
      Completeness of registration (individual procedures) was 89-96%. The median age
      was 85 years and the median follow-up time was 18 months. RESULTS: 3.8% underwent
      reoperation (any further hip surgery), most often because of implant dislocation
      or infection. The risk of reoperation (Cox regression) was higher for uncemented
      stems (hazard ratio (HR) = 1.5), mainly because of periprosthetic femoral
      fractures. Bipolar implants had a higher risk of reoperation irrespective of
      cause (HR = 1.3), because of dislocation (1.4), because of infection (1.3), and
      because of periprosthetic fracture (1.7). The risk of reoperation due to
      acetabular erosion was lower (0.30) than for unipolar implants, but reoperation
      for this complication was rare (1.7 per thousand). Procedures resulting from
      failed internal fixation had a more than doubled risk; the risk was also higher
      for males and for younger patients. The surgical approach had no influence on the
      risk of reoperation generally, but the anterolateral transgluteal approach was
      associated with a lower risk of reoperation due to dislocation (HR = 0.7). At 1
      year, the mortality was 24%. Men had a higher risk of death than women (1.8).
      INTERPRETATION: We recommend cemented hemiarthroplasties and the anterolateral
      transgluteal approach. We also suggest that unipolar implants should be used, at
      least for the oldest and frailest patients.

PMID- 22998530
TI  - Atypical femoral fracture following bisphosphonate treatment in a woman with
      osteogenesis imperfecta--a case report.

PMID- 22998531
TI  - Treatment of spontaneous osteonecrosis of the knee (SPONK) by a bisphosphonate.
AB  - BACKGROUND AND PURPOSE: Primary spontaneous osteonecrosis of the knee is a
      painful lesion in the elderly without any known cause. The onset of pain is
      usually acute. The prognosis is poor with high frequency of osteoarthritis, joint
      surface collapse, and subsequent knee surgery. In the present study, we
      determined whether bisphosphonates can prevent the joint surface collapse by
      delaying the post-necrotic remodeling. PATIENTS AND METHODS: Between 2006 and
      2009, 17 consecutive patients (mean age 68 years) with clinical and radiographic
      signs of knee osteonecrosis were identified and given alendronate, 70 mg
      perorally, once a week for a minimum of 6 months. The patients were followed
      clinically, radiographically, and by MRI. RESULTS: 10 of the 17 patients did not
      develop osteoarthritis (group A), 4 patients developed mild osteoarthritis but no
      knee joint surface collapse (group B), and 3 patients had a joint surface
      collapse (group C). 2 of the 3 patients in group C-as compared to none in the
      other groups-stopped medication prematurely, due to side effects. INTERPRETATION:
      Compared to a previous, untreated series of osteonecrosis patients at our
      hospital, the clinical results in the present series appeared better. 59% of the
      patients had a complete radiographic recovery, as compared to 25% in the original
      study. 12% were failures regarding need to undergo surgery when bisphosphonates
      were given, as compared to 32% in the previous untreated series. An anticatabolic
      drug delaying the remodeling might be an effective treatment in osteonecrosis of
      the knee but further (preferably randomized) studies are necessary.

PMID- 22998532
TI  - Regulatory network operations in the Pathway Tools software.
AB  - BACKGROUND: Biologists are elucidating complex collections of genetic regulatory
      data for multiple organisms. Software is needed for such regulatory network data.
      RESULTS: The Pathway Tools software supports storage and manipulation of
      regulatory information through a variety of strategies. The Pathway Tools
      regulation ontology captures transcriptional and translational regulation,
      substrate-level regulation of enzyme activity, post-translational modifications,
      and regulatory pathways. Regulatory visualizations include a novel diagram that
      summarizes all regulatory influences on a gene; a transcription-unit diagram, and
      an interactive visualization of a full transcriptional regulatory network that
      can be painted with gene expression data to probe correlations between gene
      expression and regulatory mechanisms. We introduce a novel type of enrichment
      analysis that asks whether a gene-expression dataset is over-represented for
      known regulators. We present algorithms for ranking the degree of regulatory
      influence of genes, and for computing the net positive and negative regulatory
      influences on a gene. CONCLUSIONS: Pathway Tools provides a comprehensive
      environment for manipulating molecular regulatory interactions that integrates
      regulatory data with an organism's genome and metabolic network. Curated
      collections of regulatory data authored using Pathway Tools are available for
      Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.

PMID- 22998533
TI  - Effects of flaxseed consumption on systemic inflammation and serum lipid profile
      in hemodialysis patients with lipid abnormalities.
AB  - Inflammation and lipid abnormalities are two important risk factors for
      cardiovascular disease in hemodialysis (HD) patients. The present study was
      designed to investigate the effects of flaxseed consumption on systemic
      inflammation and serum lipid profile in HD patients with lipid abnormalities.
      This was an unblinded, randomized clinical trial. Thirty HD patients with
      dyslipidemia (triglyceride >200 mg/dL and/or high-density lipoprotein-cholesterol
      (HDL-C) <40 mg/dL) were randomly assigned to either a flaxseed or control group.
      Patients in the flaxseed group received 40 g/day ground flaxseed for 8 weeks,
      whereas patients in the control group received their usual diet, without any
      flaxseed. At baseline and at the end of week 8, 7 mL of blood was collected after
      a 12- to 14-hour fast and serum concentrations of triglyceride, total
      cholesterol, low-density lipoprotein-cholesterol (LDL-C), HDL-C, and C-reactive
      protein (CRP) were measured. Serum concentrations of triglyceride (P < 0.01),
      total cholesterol (P < 0.01), LDL-C (P < 0.01), and CRP (P < 0.05) decreased
      significantly in the flaxseed group at the end of week 8 compared with baseline,
      whereas serum HDL-C showed a significant increase (P < 0.01). These changes in
      the flaxseed group were significant in comparison with the control group. The
      study indicates that flaxseed consumption improves lipid abnormalities and
      reduces systemic inflammation in HD patients with lipid abnormalities.

PMID- 22998534
TI  - Effects of periodontal therapy on disease activity and systemic inflammation in
      rheumatoid arthritis patients.
AB  - OBJECTIVE: This observational prospective cohort study aimed to evaluate the
      effects of non-surgical periodontal treatment on clinical periodontal
      measurements and systemic inflammatory mediator levels in low or moderate to
      highly active rheumatoid arthritis (RA) patients with chronic periodontitis.
      SUBJECTS AND METHODS: Rheumatoid arthritis activity was assessed with disease
      activity score test (DAS28). Thirty patients with RA with moderate to high
      disease activity (DAS28 >= 3.2) and chronic periodontitis (MHDA group) and thirty
      patients with RA with low disease activity (DAS28 < 3.2) and chronic
      periodontitis (LDA group) were enrolled in the study. The patients were monitored
      at the beginning and 3 months after undergoing periodontal therapy. Erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP), tumour necrosis factor-alpha
      (TNF-alpha) levels in serum, DAS28 and periodontal parameters were evaluated.
      RESULTS: Erythrocyte sedimentation rate, CRP, TNF-alpha levels in serum, DAS28
      and periodontal parameters exhibited similar and significant reduction 3 months
      after the non-surgical periodontal treatment. CONCLUSION: Non-surgical
      periodontal treatment may prove beneficial in reducing RA severity as measured by
      ESR, CRP, TNF-alpha levels in serum and DAS28 in low or moderate to highly active
      RA patients with chronic periodontitis.

PMID- 22998535
TI  - Wells' syndrome associated with Churg-Strauss syndrome: correlation with mast
      cell distribution.

PMID- 22998536
TI  - Baclofen for the treatment of alcohol dependence.
AB  - The amino acid gamma-aminobutyric acid (GABA) is the major inhibitory
      neurotransmitter in the nervous system. The mesolimbic dopamine system is a major
      component of the brain's reward pathways, and GABA neurons are part of this
      system, decreasing the activity of dopamine neurons through the inhibitory
      effects of GABA-B receptors. Because the mesolimbic dopamine system has been
      linked to the reinforcing effects of alcohol and other drugs of abuse, baclofen
      (Lioresal((r)), Gablofen((r))), a GABA-B receptor agonist drug, has been
      investigated in preclinical studies as a potential treatment for addictions.
      Baclofen reduces the reinforcing effects of alcohol and other drugs in animals,
      providing justification for clinical studies in human beings. Two open-label and
      two placebo-controlled studies in humans found that baclofen was effective for
      reducing alcohol craving and intake, but one placebo-controlled study found no
      benefit for baclofen. Baclofen is a safe and well-tolerated novel drug treatment
      for alcohol dependence.

PMID- 22998537
TI  - Reducing use of restraints and seclusion to create a culture of safety.
AB  - The purpose of this article is to describe the structure that empowered staff of
      a locked community hospital unit to reduce the use of restraints and seclusion to
      create a culture of safety. Themes garnered from interviews with and observations
      of key informants fit into the categories of a structural empowerment model, with
      leadership creating opportunities available for staff to develop new knowledge,
      information on trauma-informed care, support for feedback, and resources for the
      unit; thus, relationships with patients flourished. In turn, staff engaged in
      relationships with patients to provide opportunities to develop new knowledge and
      offer information, support, and resources.

PMID- 22998538
TI  - Treatment of alcohol-dependent college students.
AB  - A report by the Centers for Disease Control and Prevention noted that excessive
      alcohol consumption is responsible for more than 4,600 deaths in underage youth
      annually. Alcohol abuse is common among college-age youth and may progress to
      alcohol dependence, which includes tolerance, craving, physical dependence, and
      loss of control. Although treatment for alcohol dependence is effective, like all
      other chronic disorders, relapse is common. The purpose of this article is to
      examine the issues surrounding alcohol abuse and dependence as well as
      maintaining sobriety in light of the high-risk college student drinking
      environment.

PMID- 22998539
TI  - Adolescents, gangs, and perceptions of safety, parental engagement, and peer
      pressure.
AB  - Adolescents are exposed to various forms of gang violence, and such exposure has
      led them to feel unsafe in their neighborhood and have differing interactions
      with their parents and peers. This qualitative study explored adolescents',
      parents', and community center employees' perceptions of adolescents' interaction
      with their neighborhood, family, and peers. Three themes emerged from the data:
      Most adolescents reported that the community center provided a safe environment
      for them; parental engagement influenced adolescents' experiences with gangs; and
      adolescents were subjected to peer pressure in order to belong. Exposure to gang
      violence can leave an impression on adolescents and affect their mental health,
      but neighborhood safety and relationships with parents and peers can influence
      adolescents' exposure to gang violence. Recommendations regarding the use of
      health care professionals at community centers are proposed.

PMID- 22998540
TI  - Catalyst-controlled regioselectivity in the synthesis of branched conjugated
      dienes via aerobic oxidative Heck reactions.
AB  - Pd-catalyzed aerobic oxidative coupling of vinylboronic acids and electronically
      unbiased alkyl olefins provides regioselective access to 1,3-disubstituted
      conjugated dienes. Catalyst-controlled regioselectivity is achieved by using 2,9
      dimethylphenanthroline as a ligand. The observed regioselectivity is opposite to
      that observed from a traditional (nonoxidative) Heck reaction between a vinyl
      bromide and an alkene. DFT computational studies reveal that steric effects of
      the 2,9-dimethylphenanthroline ligand promote C-C bond formation at the internal
      position of the alkene.

PMID- 22998541
TI  - Cutaneous adverse events associated with heparin.
AB  - Heparin use is associated with various cutaneous reactions, with the most common
      being immune-mediated skin lesions and bleeding complications. In this review, we
      compile the dermatological side-effects of heparin reported in the literature,
      and provide a clear approach to their adequate management.

PMID- 22998542
TI  - Extending psychosocial assessment of patients with psoriasis in the UK, using a
      self-rateds, web-based survey.
AB  - BACKGROUND: Quality of life self-rating using a web-based survey has not
      previously been evaluated for psoriasis in the UK. AIM: To use an open-access web
      based survey to assess the effect of psoriasis on patients' daily life. Methods. 
      The survey was conducted using a dedicated website endorsed by a UK psoriasis
      patient charity. RESULTS: In total, 1760 patients (1102 women, 658 men; median
      age range 40-44 years) assessed their psoriasis using the website. Psoriasis was
      'very' or 'extremely' active in 52%, and 71% had been diagnosed > 10 years
      previously. Psoriasis had negatively affected the working life of 59% of
      patients, and the educational performance of 31%. CONCLUSIONS: The use of an open
      access web-based survey may address potential bias in previous studies, but may
      itself introduce a bias towards younger patients. This is the first report of a
      web-based survey of UK patients with psoriasis, providing further recent evidence
      of how psoriasis affects patients' lives.

PMID- 22998543
TI  - Altered gene expression in squamous cell carcinoma arising from congenital
      unilateral linear porokeratosis.
AB  - Congenital unilateral linear porokeratosis (CULP) is a rare disorder of
      keratinization that shares clinical and molecular similarities with psoriasis. It
      also has an increased risk for malignant transformation to cutaneous squamous
      cell carcinoma (SCC). We investigated the expression of psoriasin, human beta
      defensin-2, cathelicidin antimicrobial peptide/LL-37, e-cadherin, involucrin,
      p16(INK4a) , p53, cyclin D1 and microchromosome maintenance protein 7 in healthy
      skin and in lesions of psoriasis, CULP and SCC from the same patient. p16(INK4a) 
      was overexpressed in CULP but not in the subsequent SCC. Psoriasin was
      overexpressed in psoriasis, CULP and SCC compared with healthy skin.
      Speculatively, p16(INK4a)  and psoriasin could be involved in the pathogenesis of
      CULP. Moreover, psoriasin may play a role in the malignant transformation of CULP
      to SCC.

PMID- 22998544
TI  - Is there still a role for psoralen ultraviolet A in the treatment of chronic hand
      eczema?

PMID- 22998545
TI  - A large pigmented lesion mimicking malignant melanoma.

PMID- 22998546
TI  - Severe Rowell syndrome associated with oral terbinafine.

PMID- 22998547
TI  - John Templeton Bowen, MD, 1857-1940: the centenary of his most famous
      publication.

PMID- 22998548
TI  - Draft whole genome sequence of the cyanide-degrading bacterium Pseudomonas
      pseudoalcaligenes CECT5344.
AB  - Pseudomonas pseudoalcaligenes CECT5344 is a Gram-negative bacterium able to
      tolerate cyanide and to use it as the sole nitrogen source. We report here the
      first draft of the whole genome sequence of a P. pseudoalcaligenes strain that
      assimilates cyanide. Three aspects are specially emphasized in this manuscript.
      First, some generalities of the genome are shown and discussed in the context of
      other Pseudomonadaceae genomes, including genome size, G + C content, core genome
      and singletons among other features. Second, the genome is analysed in the
      context of cyanide metabolism, describing genes probably involved in cyanide
      assimilation, like those encoding nitrilases, and genes related to cyanide
      resistance, like the cio genes encoding the cyanide insensitive oxidases.
      Finally, the presence of genes probably involved in other processes with a great
      biotechnological potential like production of bioplastics and biodegradation of
      pollutants also is discussed.

PMID- 22998549
TI  - Why only some plants emit isoprene.
AB  - Isoprene (2-methyl-1,3-butadiene) is emitted from many plants and it appears to
      have an adaptive role in protecting leaves from abiotic stress. However, only
      some species emit isoprene. Isoprene emission has appeared and been lost many
      times independently during the evolution of plants. As an example, our
      phylogenetic analysis shows that isoprene emission is likely ancestral within the
      family Fabaceae (= Leguminosae), but that it has been lost at least 16 times and
      secondarily gained at least 10 times through independent evolutionary events.
      Within the division Pteridophyta (ferns), we conservatively estimate that
      isoprene emissions have been gained five times and lost two times through
      independent evolutionary events. Within the genus Quercus (oaks), isoprene
      emissions have been lost from one clade, but replaced by a novel type of light
      dependent monoterpene emissions that uses the same metabolic pathways and
      substrates as isoprene emissions. This novel type of monoterpene emissions has
      appeared at least twice independently within Quercus, and has been lost from 9%
      of the individuals within a single population of Quercus suber. Gain and loss of
      gene function for isoprene synthase is possible through relatively few mutations.
      Thus, this trait appears frequently in lineages; but, once it appears, the time
      available for evolutionary radiation into environments that select for the trait
      is short relative to the time required for mutations capable of producing a non
      functional isoprene synthase gene. The high frequency of gains and losses of the
      trait and its heterogeneous taxonomic distribution in plants may be explained by
      the relatively few mutations necessary to produce or lose the isoprene synthase
      gene combined with the assumption that isoprene emission is advantageous in a
      narrow range of environments and phenotypes.

PMID- 22998550
TI  - Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic
      cancer cells.
AB  - BACKGROUND: Pancreatic cancer remains the deadliest of all cancers, with a
      mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic
      standard, but only marginally improves life-span due to its chemical instability
      and low cell penetrance. A new paradigm to improve Gemcitabine's therapeutic
      index is to administer it in nanoparticles, which favour its delivery to cells
      when under 500 nm in diameter. Although promising, this approach still suffers
      from major limitations, as the choice of nanovector used as well as its effects
      on Gemcitabine intracellular trafficking inside pancreatic cancer cells remain
      unknown. A proper elucidation of these mechanisms would allow for the elaboration
      of better strategies to engineer more potent Gemcitabine nanotherapeutics against
      pancreatic cancer. METHODS: Gemcitabine was encapsulated in two types of commonly
      used nanovectors, namely poly(lactic-co-glycolic acid) (PLGA) and cholesterol
      based liposomes, and their physico-chemical parameters assessed in vitro. Their
      mechanisms of action in human pancreatic cells were compared with those of the
      free drug, and with each others, using cytotoxity, apoptosis and ultrastructural
      analyses. RESULTS: Physico-chemical analyses of both drugs showed high loading
      efficiencies and sizes of less than 200 nm, as assessed by dynamic light
      scattering (DLS) and transmission electron microscopy (TEM), with a drug release
      profile of at least one week. These profiles translated to significant
      cytotoxicity and apoptosis, as well as distinct intracellular trafficking
      mechanisms, which were most pronounced in the case of PLGem showing significant
      mitochondrial, cytosolic and endoplasmic reticulum stresses. CONCLUSIONS: Our
      study demonstrates how the choice of nanovector affects the mechanisms of drug
      action and is a crucial determinant of Gemcitabine intracellular trafficking and
      potency in pancreatic cancer settings.

PMID- 22998551
TI  - Novel FabH inhibitors: a patent and article literature review (2000--2012).
AB  - INTRODUCTION: The traditional antimicrobial chemotherapy drugs play their effects
      mostly via bacterial interference with in vivo amino acids, nucleotides, amino
      sugars and other small molecule synthesis, or interfering the biochemical
      processes of these small molecules to synthesize nucleic acids, peptidoglycan and
      other biological macromolecules. In recent years, enzymes with single function in
      bacterial fatty acid synthetase system have become the genome-driven novel
      antibacterial drug targets. Among inhibitors of these targets, FabH inhibitors
      are distinguished, for their target is different from that of existing
      antibiotics. Therefore, discovery of FabH inhibitors might be a potential
      orientation to overcome bacterial resistance. AREAS COVERED: This review
      summarized new patents and articles published on FabH inhibitors from 2000 to
      2012. EXPERT OPINION: The review gives a brief understanding about the background
      and development in the area of FabH inhibitors that aims to solve the bacterial
      resistance problem. This review puts emphasis on some typical small molecules,
      which participate in the process of FabH inhibition. Overall, the research scopes
      of antibacterial agents are getting broad. Fatty acid synthase (FAS) pathway has
      been proved to be a promising target for the therapy. However, claim of novel
      antibacterial agents with more active and higher specificity is still continued.

PMID- 22998553
TI  - Sodium dodecyl sulfate at water-hydrophobic interfaces: a simulation study.
AB  - Using molecular dynamics simulations, we have studied the water-vapor and water
      oil (decane) interfaces of aqueous solutions of sodium dodecyl sulfate (SDS). The
      water-vapor interface is often used as a model for water-oil (hydrophobic)
      interfaces, yet we observe that the behavior of amphiphilic DS(-) ions at these
      two interfaces is very different. Specifically, on a water-vapor interface, SDS
      forms aggregates at low coverages, while it is homogeneously distributed on the
      water-oil interface. Two decane parametrizations resulted in dramatically
      different conformations: decane parametrized based on a GROMOS force field
      "froze", while decane parametrized with a TraPPE force field remained liquid at
      300 K. The calculated effective second-order susceptibilities and nonlinear sum
      frequency scattering intensities of DS(-) ions at the "frozen" decane-water agree
      well with experimental data of DS(-) ions at the hexadecane droplet-water
      interface. This suggests that the orientation of longer alkane molecules is
      predominantly parallel to the interface and that, at low coverages, DS(-) ions
      follow the orientation of oil molecules.

PMID- 22998552
TI  - Vibration thresholds are increased at low frequencies in the sole of the foot in
      diabetes-a novel multi-frequency approach.
AB  - AIMS: To evaluate multi-frequency tactilometry as a method to measure
      vibrotactile sense in the sole of the foot in subjects with diabetes. METHODS:
      Vibration thresholds were investigated at five frequencies (8, 16, 32, 64 and 125
      Hz) at three sites (first and fifth metatarsal heads and heel) in the sole of the
      foot in subjects with Type 1 and Type 2 diabetes (n = 37). Thresholds were
      compared with healthy, age- and gender-matched subjects (n = 37) and related to
      glycaemic levels, subjective estimation of sensation in the feet and to
      perception of touch. RESULTS: Vibration thresholds were significantly higher in
      subjects with diabetes compared with healthy subjects at low frequencies (8, 16
      and 32 Hz) at all measured sites, and also at 64 Hz for the metatarsal heads.
      Perception of touch and subjective estimation of sensation were significantly
      impaired in subjects with diabetes. Glycaemic levels, which were higher in
      subjects with diabetes, did not correlate with vibration thresholds at 32 Hz
      (most sensitive to Meissner's corpuscles) or with touch thresholds in subjects
      with diabetes. Vibration thresholds at 32 Hz correlated significantly with
      perception of touch (rho = 0.45-0.65; P < 0.01) and with subjective sensation
      (rho = -0.38 to -0.52; P < 0.001) in subjects with diabetes. Perception of touch
      and subjective estimation of sensation did also correlate (rho = -0.51 to -0.80;
      P < 0.002). CONCLUSIONS: Tactilometry is effective in detecting neuropathy in the
      sole of the foot at low frequencies of mainly 8-32 Hz, indicating that at least
      Meissner's corpuscles, or their related large nerve fibres, are affected by
      diabetes.

PMID- 22998554
TI  - Cardiorespiratory fitness and heart rate recovery in obese premenopausal women.
AB  - Post-exercise heart rate recovery (HRR) has been proposed as a measure of cardiac
      autonomic dysfunction in apparently healthy adults. We aimed to determine the
      effects of a lifestyle intervention on HRR among clinically obese premenopausal
      women. A randomized controlled trial was conducted to investigate the effects of
      a 3-month non-dieting lifestyle intervention program on cardiorespiratory fitness
      (CRF) and HRR among healthy clinically obese premenopausal women. Thirty-one were
      randomly assigned to 3-month intensive lifestyle intervention and 31 served as
      controls. Sixty-one participants performed a maximal treadmill walking test with
      metabolic gas exchange. Baseline anthropometric measures were closely related to
      HRR at 1 min, which may indicate reduced parasympathetic reactivation. Post
      exercise HRR at 60 s (HRR60) increased from 21.3 +/- 6.2 to 27.8 +/- 10.2 bpm in
      the intervention group compared with a smaller reduction (26.8 +/- 12.3 to 24.5
      +/- 9.9 bpm) in controls (test for interaction P = 0.0001). HRR120 showed a
      significant effect of time (P = 0.0002) with no significant interaction with
      lifestyle intervention. A significant increase in VO2 peak was evident in the
      lifestyle group (21.6 to 23.6 mL/kg/min) compared with a modest reduction in the
      controls (22.6 to 21.6 mL/kg/min; test for interaction, P = 0.001). Clinically
      obese healthy premenopausal women achieved significant improvements in HRR60 and
      VO peak following a 3-month intensive lifestyle intervention.

PMID- 22998555
TI  - Pathogen-induced Caenorhabditis elegans developmental plasticity has a hormetic
      effect on the resistance to biotic and abiotic stresses.
AB  - BACKGROUND: Phenotypic plasticity, i.e. the capacity to change the phenotype in
      response to changes in the environment without alteration of the genotype, is
      important for coping with unstable environments. In spite of the ample evidence
      that microorganisms are a major environmental component playing a significant
      role in eukaryotic organisms health and disease, there is not much information
      about the effect of microorganism-induced developmental phenotypic plasticity on
      adult animals' stress resistance and longevity. RESULTS: We examined the
      consequences of development of Caenorhabditis elegans larvae fed with different
      bacterial strains on stress resistance and lifespan of adult nematodes. Bacterial
      strains used in this study were either pathogenic or innocuous to nematodes.
      Exposure to the pathogen during development did not affect larval survival.
      However, the development of nematodes on the pathogenic bacterial strains
      increased lifespan of adult nematodes exposed to the same or a different
      pathogen. A longer nematode lifespan, developed on pathogens and exposed to
      pathogens as adults, did not result from an enhanced capacity to kill bacteria,
      but is likely due to an increased tolerance to the damage inflicted by the
      pathogenic bacteria. We observed that adult nematodes developed on a pathogen
      induce higher level of expression of the hsp-16.2 gene and have higher resistance
      to heat shock than nematodes developed on an innocuous strain. Therefore, the
      increased resistance to pathogens could be, at least partially, due to the early
      induction of the heat shock response in nematodes developed on pathogens. The
      lifespan increase is controlled by the DBL-1 transforming growth factor beta
      like, DAF-2/DAF-16 insulin-like, and p38 MAP kinase pathways. Therefore, the
      observed modulation of adult nematode lifespans by developmental exposure to a
      pathogen is likely a genetically controlled response. CONCLUSIONS: Our study
      shows that development on pathogens has a hormetic effect on adult nematodes, as
      it results in increased resistance to different pathogens and to heat shock. Such
      developmental plasticity of C. elegans nematodes, which are self-fertilizing
      homozygous animals producing offspring with negligible genetic variation, could
      increase the probability of survival in changing environments.

PMID- 22998557
TI  - Jagged1-mediated Notch signaling regulates mammalian inner ear development
      independent of lateral inhibition.
AB  - CONCLUSION: Jagged1-mediated Notch signaling regulates hair cell (HC) production
      in a distinct way rather than lateral inhibition mediated by Hes1 and Hes5.
      Jagged1 may interact with Notch3, probably via candidate downstream mediators
      Hesr1 and Hesr2, regulating the prosensory formation in the early stage.
      OBJECTIVES: To explore the function of the Jagged1-mediated Notch signaling
      pathway in mammalian inner ear development and its possible mechanism. METHODS:
      Using conditional gene targeting, a novel Jagged1 conditional knockout (Jag1
      cko), Pax8(cre/+); Jag1(flox/flox), was established. The auditory brainstem
      response and swim ability test were utilized to identify functional disability.
      The expression of Jagged1, Notch3, Hes1, Hesr1, and Hesr2 was detected by
      immunofluorescence and immunohistochemistry. RESULTS: Our Jag1-cko model was
      established and survived well. It presented hearing impairment and balance
      disturbance with 'waltzing' behavior. Cochleae and vestibular apparatus were all
      found in our Jag1-cko model. Patch deficiency of outer hair cells (OHCs) was
      found on the apical and middle turns of the auditory epithelium. OHCs were
      totally missing on the basal turn. The stereociliary bundles were disorientated
      on the cristae. Unlike Hes1, no expression of Notch3, Hesr1, and Hesr2 was found
      on embryonic day 13.5 of the Jag1-cko model.

PMID- 22998556
TI  - Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups.
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder
      characterized by chronic abdominal pain associated with alterations in bowel
      function. Given the heterogeneity of the symptoms, multiple pathophysiologic
      factors are suspected to play a role. We classified women with IBS into four
      subgroups based on distinct symptom profiles. In-depth shotgun proteomic analysis
      was carried out to profile the urinary proteomes to identify possible proteins
      associated with these subgroups. First void urine samples with urine creatinine
      level>=100 mg/dL were used after excluding samples that tested positive for
      blood. Urine from 10 subjects representing each symptom subgroup was pooled for
      proteomic analysis. The urine proteome was analyzed by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) using a data-independent method known as
      Precursor Acquisition Independent From Ion Count (PAcIFIC) that allowed extended
      detectable dynamic range. Differences in protein quantities were determined by
      peptide spectral counting followed by validation of select proteins with ELISA or
      a targeted single reaction monitoring (LC-SRM/MS) approach. Four IBS symptom
      subgroups were selected: (1) Constipation, (2) Diarrhea+Low Pain, (3)
      Diarrhea+High Pain, and (4) High Pain+High Psychological Distress. A fifth group
      consisted of Healthy Control subjects. From comparisons of quantitative spectral
      counting data among the symptom subgroups and controls, a total of 18 proteins
      that showed quantitative differences in relative abundance and possible
      physiological relevance to IBS were selected for further investigation. Three of
      the 18 proteins were chosen for validation by either ELISA or SRM. An elevated
      expression of gelsolin (GSN) was associated with the high pain groups. Trefoil
      Factor 3 (TFF3) levels were higher in IBS groups compared to controls. In this
      study, the IBS patients subclassified by predominant symptoms showed differences
      in urine proteome levels. Proteins showing distinctive changes are involved in
      homeostasis of intestinal function and inflammatory response. These findings
      warrant future studies with larger, independent cohorts to enable more extensive
      assessment and validation of urinary protein markers as a diagnostic tool in
      adults with IBS.

PMID- 22998558
TI  - Assessment of Meniere's disease from a radiological aspect - saccular otoconia as
      a cause of Meniere's disease?
AB  - CONCLUSION: Significant reduced visualization of the reuniting duct (ductus
      reuniens; RD), saccular duct (SD) and endolymphatic sinus (ES) in Meniere's
      disease (MD) compared with normal control ears on three-dimensional (3D) CT
      imaging suggests the blockage of endolymphatic flow there with radiodense
      substances, which may be explained by dislodged otoconia from the saccule. These
      structures could be involved in the pathogenesis of MD. OBJECTIVE: This study was
      designed to visualize and assess the RD, SD and ES in patients with MD using 3D
      CT. METHODS: Sixty-two patients with a definite diagnose of unilateral MD, based
      on criteria proposed by the Committee on Hearing and Equilibrium of the American
      Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), were compared with
      contralateral ears and normal controls (26 ears) using 3D CT. The RD, SD and ES
      were scrutinized for patency on 3D CT images. RESULTS: MD ears showed loss of
      continuity of the RD, SD and ES based on evaluation of 3D CT images, and differed
      significantly from normal healthy control ears (p < 0.01).

PMID- 22998559
TI  - Efficacy of multidrug superselective intra-arterial chemotherapy (docetaxel,
      cisplatin, and 5-fluorouracil) using the Seldinger technique for tongue cancer.
AB  - CONCLUSION: This therapy produced better results than intravenous multidrug
      chemotherapy (CF therapy, CPF therapy, etc.) or superselective intra-arterial
      chemotherapy (SIC) alone with cisplatin (CDDP) and 5-fluorouracil (5-FU). Primary
      tumor may be controlled by SIC alone in cases of T2 and many cases of T3 tumors,
      and by the combination of SIC and concurrent radiotherapy in cases of T3 and many
      cases of T4a. Cervical lymph node metastasis was treated with neck dissection in
      some patients. The results indicate that this therapy is useful to control
      primary tumor without resection for organ preservation. OBJECTIVES: This therapy
      was intended to control primary tumor without resection for better quality of
      life (QOL). METHODS: A total of 45 patients with primary squamous cell carcinoma
      of the tongue were included in the study. SIC with docetaxel, cisplatin, and 5-FU
      was administered. RESULTS: In terms of the primary response of primary tumor, 43
      patients achieved a clinical complete response (CR). Moreover, in these patients
      no cancer cells were histopathologically found by biopsy, resulting in a response
      rate of 100% and a CR rate of 95.6%. During the median follow-up period of 1779
      days (59 months) (range 110-3752 days), the 5-year survival rate and organ
      preservation rate were 89.8% and 80.7%, respectively.

PMID- 22998560
TI  - Dinuclear ruthenium nitrido complexes supported by an oxygen tripodal ligand.
AB  - Dinuclear ruthenium nitrido complexes supported by the Klaui's tripodal ligand
      [CpCo{P(O)(OEt)(2)}(3)](-) (L(OEt)(-)) have been synthesized starting from the
      ruthenium(VI) nitrido precursor [L(OEt)Ru(VI)(N)Cl(2)] (1). Heating a solution of
      1 in CCl(4) at reflux, followed by recrystallization from hexane under nitrogen,
      afforded the mixed-valence ruthenium(V)-ruthenium(IV) MU-nitrido complex
      [L(OEt)Cl(2)Ru(V)(MU-N)Ru(IV)Cl(2)L(OEt)] (2). The cyclic voltammogram of 2
      exhibited reversible couples at 0.19 and 1.13 V versus Cp(2)Fe(+/0), which are
      assigned as the Ru(V)-Ru(IV)/Ru(IV)-Ru(IV) and Ru(V)-Ru(V)/Ru(V)-Ru(IV) couples,
      respectively. Recrystallization of 2 from Et(2)O/heptane in air yielded the
      diamagnetic Ru(IV)-Ru(IV) complex [H(13)O(6)][{L(OEt)Ru(IV)Cl(2)}(2)(MU-N)]
      ([H(13)O(6)][2]), which underwent cation exchange with n-Bu(4)NOH to give [n
      Bu(4)N][2]. X-ray diffraction revealed that the complex anions in [H(13)O(6)][2]
      and [n-Bu(4)N][2] contain linear, symmetric Ru-N-Ru bridges. Treatment of 1 with
      [(eta(6)-p-cymene)Ru(II)Cl(2)](2) in benzene afforded the tetranuclear
      ruthenium(IV) complex [L(OEt)Cl(2)Ru(IV)(MU-N)Ru(IV)(H(2)O)Cl(2)](2) (3)
      containing symmetric Ru(IV)-N-Ru(IV) bridges. The reaction of 1 with
      [Ru(II)(H)(Cl)(CO)(PCy(3))(2)] (Cy = cyclohexyl) gave the ruthenium(VI)
      ruthenium(II) nitrido complex [L(OEt)Cl(2)Ru(VI)(MU-N)Ru(II)(H)Cl(CO)(PCy(3))(2)]
      (4). The observed short Ru(II)-N bond distance [1.915(5) A] and high C-O
      stretching frequency (1985 cm(-1)) in 4 are suggestive of pi interaction between
      Ru(II) and the nitride.

PMID- 22998561
TI  - The blue light receptor complex WC-1/2 of Schizophyllum commune is involved in
      mushroom formation and protection against phototoxicity.
AB  - Blue light is necessary for initiation of mushroom formation in Schizophyllum
      commune. The genome of this basidiomycete contains homologues of the blue light
      receptor genes wc-1 and wc-2 of Neurospora crassa. Here, it is shown that
      inactivation of either or both of these genes in S. commune results in a blind
      phenotype. Mushroom formation was abolished in dikaryons and they formed
      symmetrical instead of asymmetrical colonies. Development was restored in a
      temperature dependent way in a Deltawc-2Deltawc-2 strain by introducing a
      construct encompassing the wc-2 gene under control of the promoter of the heat
      shock gene hsp3. A genome-wide expression analysis showed that the transcription
      factor genes c2h2 and hom1 as well as many hydrophobin genes are downregulated in
      light-grown colonies of the Deltawc-2Deltawc-2 mutant when compared with the wild
      type dikaryon. Inactivation of wc-1 and/or wc-2 also resulted in sensitivity of
      the mycelium to intense light. Monokaryotic mutant strains only survived exposure
      to 6500 lux of light by growing into the agar. Expression analysis indicates that
      the photosensitivity of the Deltawc-1 and Deltawc-2 strains is due to lower
      levels of photolyase and ferrochelatase.

PMID- 22998562
TI  - Protection by hydrogen against gamma ray-induced testicular damage in rats.
AB  - The aim of this study was to investigate the possible protective role of hydrogen
      rich saline solution (HRSS) and WR-2721 on the testicular damage induced by
      irradiation. Sprague-Dawley rats were randomly divided into four groups. Group I
      served as control group. Rats in group II were exposed to the irradiation. The
      animals in group III and IV were injected intraperitoneally with HRSS (5 ml/kg)
      and WR-2721 (200 mg/kg), respectively, 15 min. before the start of gamma
      irradiation. Testis weight, testis dimensions, sperm count, sperm motility,
      apoptosis index and biochemical assays were assessed after a 4-day initiation of
      irradiation. Testis weight, testis dimensions, sperm count, sperm motility in
      group II were significantly lower compared with those in the control group,
      whereas they were higher in the HRSS and WR-2721 group. Apoptosis index was
      significantly increased in group II. Treatment of rats with HRSS and WR-2721
      significantly reduced the apoptosis index. On the other hand, irradiation
      markedly decreased activities of SOD. Activities of SOD were significantly
      improved when treated with HRSS and WR-2721. Significant increase in the MDA
      level was observed in group II. MDA levels of group III and IV were significantly
      lowered when compared with group II. HRSS also played a significant role in the
      recovery of serum testosterone levels. The results from this experimental study
      suggest that hydrogen has a possible protective effect against radiation-induced
      testicular damage.

PMID- 22998563
TI  - Fe/N/C composite in Li-O2 battery: studies of catalytic structure and activity
      toward oxygen evolution reaction.
AB  - Atomically dispersed Fe/N/C composite was synthesized and its role in controlling
      the oxygen evolution reaction during Li-O(2) battery charging was studied by use
      of a tetra(ethylene glycol) dimethyl ether-based electrolyte. Li-O(2) cells using
      Fe/N/C as the cathode catalyst showed lower overpotentials than alpha
      MnO(2)/carbon catalyst and carbon-only material. Gases evolved during the charge
      step contained only oxygen for Fe/N/C cathode catalyst, whereas CO(2) was also
      detected in the case of alpha-MnO(2)/C or carbon-only material; this CO(2) was
      presumably generated from electrolyte decomposition. Our results reiterate the
      catalytic effect in reducing overpotentials, which not only enhances battery
      efficiency but also improves its lifespan by reducing or eliminating electrolyte
      decomposition. The structure of the Fe/N/C catalyst was characterized by
      transmission electron microscopy, scanning transmission electron microscopy,
      inductively coupled plasma optical emission spectroscopy, and X-ray absorption
      spectroscopy. Iron was found to be uniformly distributed within the carbon
      matrix, and on average, Fe was coordinated by 3.3 +/- 0.6 and 2.2 +/- 0.3 low Z
      elements (C/N/O) at bond distances of ~1.92 and ~2.09 A, respectively.

PMID- 22998564
TI  - Prognostic significance of 5-fluorouracil metabolism-relating enzymes and
      enhanced chemosensitivity to 5-fluorouracil by 5-chloro 2,4-dihydroxy-pyridine in
      urothelial carcinoma.
AB  - BACKGROUND: Recently, S-1, a novel 5-fluorouracil (5-FU)-based agent containing
      the strong dihydropyrimidine dehydrogenase (DPD) inhibitor, 5-chloro-2,4
      dihydropyrimidine (CDHP) has been clinically used to treat various non-urothelial
      carcinomas (UC). High levels of thymidylate synthase (TS), the target enzyme of 5
      FU and DPD which degrades the majority of 5-FU, are associated with poor
      prognosis in some cancers. However, only a few reports have dealt with this in
      UC. The aim of this study was to investigate the clinical significance of TS and
      DPD in upper tract urothelial carcinoma (UTUC) and evaluate the role of TS and
      DPD on the sensitivity of 5-FU in UC cell lines and the anti-tumor effect of S-1
      in UC xenograft model. METHODS: Firstly, we evaluated the immunohistochemical
      expression of TS and DPD in 176 patients with UTUC to determine their prognostic
      significance. Secondly, the levels of TS and DPD in UC cell lines were measured
      by ELISA and real-time PCR. Furthermore, the association between their levels and
      the sensitivity to 5-FU was examined using the small interfering RNA (siRNA)
      specific for TS and DPD. Thirdly, the anti-tumor effect of S-1 was evaluated in
      UC xenograft model. RESULTS: Immunohistochemical evaluation of TS and DPD in UTUC
      human samples revealed that TS expression was significantly associated with
      stage, grade, and lymphovascular invasion and DPD expression was significantly
      associated with grade. Multivariate analysis revealed that high TS expression was
      an independent predictor of disease-specific survival in them. In in vitro study
      using UC cell lines, high levels of TS and DPD were associated with low response
      to 5-FU and these associations were confirmed with siRNA specific for TS and DPD.
      In in vivo study using UC xenograft model, S-1 treatment dramatically inhibited
      tumor growth compared to controls, tegafur, or UFT in UC tumor with a high level
      of DPD. CONCLUSIONS: TS plays an important role in the prognosis of UTUC and S-1
      may be a key agent for UC tumor, especially with a high level of DPD.

PMID- 22998565
TI  - Mutants impaired in vacuolar metal mobilization identify chloroplasts as a target
      for cadmium hypersensitivity in Arabidopsis thaliana.
AB  - Cadmium (Cd) is highly toxic to plants causing growth reduction and chlorosis. It
      binds thiols and competes with essential transition metals. It affects major
      biochemical processes such as photosynthesis and the redox balance, but the
      connection between cadmium effects at the biochemical level and its deleterious
      effect on growth has seldom been established. In this study, two Cd
      hypersensitive mutants, cad1-3 impaired in phytochelatin synthase (PCS1), and
      nramp3nramp4 impaired in release of vacuolar metal stores, have been compared.
      The analysis combines genetics with measurements of photosynthetic and
      antioxidant functions. Loss of AtNRAMP3 and AtNRAMP4 function or of PCS1 function
      leads to comparable Cd sensitivity. Root Cd hypersensitivities conferred by cad1
      3 and nramp3nramp4 are cumulative. The two mutants contrast in their tolerance to
      oxidative stress. In nramp3nramp4, the photosynthetic apparatus is severely
      affected by Cd, whereas it is much less affected in cad1-3. In agreement with
      chloroplast being a prime target for Cd toxicity in nramp3nramp4, the Cd
      hypersensitivity of this mutant is alleviated in the dark. The Cd
      hypersensitivity of nramp3nramp4 mutant highlights the critical role of vacuolar
      metal stores to supply essential metals to plastids and maintain photosynthetic
      function under Cd and oxidative stresses.

PMID- 22998567
TI  - Current advances in the synthesis and antitumoral activity of SIRT1-2 inhibitors
      by modulation of p53 and pro-apoptotic proteins.
AB  - Four different classes of HDACs have been identified in humans so far. Classes I,
      II and IV are zinc-dependent amidohydrolases, while III is a family of
      phylogenetically conserved NAD-dependent protein deacetylases/ADP
      ribosyltransferase with a well-defined role in modifying chromatin conformation
      and altering the accessibility of the damaged sites of DNA for repair enzymes.
      Sirtuins are histone deacetylases (HDACs) of class III that cleave off acetyl
      groups from acetyl-lysine residues in histones and non-histone proteins. As
      sirtuins are involved in many physiological and pathological processes, their
      activity has been associated with different human diseases, including cancer.
      Especially two sirtuin members, SIRT1 and SIRT2, have been found to antagonize
      p53-dependent transcriptional activation and apoptosis in response to DNA damage
      by catalyzing p53 deacetylation. The findings that SIRT1 levels are increased in
      a number of tumors highlight the oncogenic role of sirtuins, in particular, in
      the down-modulation of p53 oncosuppressor activity. Along this lane, cancers
      carrying wild-type (wt) p53 protein are known to deregulate its activity by other
      mechanisms. Therefore, inhibition of SIRT1 and SIRT2, aimed at restoring wt-p53
      transcriptional activity in tumors that retain the ability to express normal p53,
      might represent a valid therapeutic cancer approach specially when combined with
      standard therapies. This review will be focused on sirtuin inhibitors, with a
      specific attention on inhibitors of SIRT1 and SIRT2. Among them, nicotinamide and
      its analogs, sirtinol, A3 and M15, splitomicin, HR73 and derivatives, cambinol
      and derivatives, EX 527, kinase inhibitors, suramin, 4-dihydropyridine
      derivatives, tenovins, TRIPOS 360702, AC 93253, 3-arylideneindolinones, CSC8 and
      CSC13 will also be described.

PMID- 22998566
TI  - Natural Modulators of Amyloid-Beta Precursor Protein Processing.
AB  - Alzheimer?s disease (AD) is a devastating neurodegenerative disease and the
      primary cause of dementia, with no cure currently available. The pathogenesis of
      AD is believed to be primarily driven by A&#946;, the principal component of
      senile plaques. A&#946; is an ~4 kDa peptide generated from the amyloid-&#946;
      precursor protein (APP) through proteolytic secretases. Natural products,
      particularly those utilized in traditional Chinese medicine (TCM), have a long
      history alleviating common clinical disorders, including dementia. However, the
      cell/molecular pathways mediated by these natural products are largely unknown
      until recently when the underlying molecular mechanisms of the disorders begin to
      be elucidated. Here, the mechanisms with which natural products modulate the
      pathogenesis of AD are discussed, in particular, by focusing on their roles in
      the processing of APP.

PMID- 22998568
TI  - Flavonoids acting on DNA topoisomerases: recent advances and future perspectives
      in cancer therapy.
AB  - Flavonoids, secondary metabolites ubiquitously produced in the plant kingdom, are
      low molecular weight polyphenolic molecules. They are characterized by variable
      chemical structures and show a vast array of biological activities (i.e...
      antiviral, antiinflammatory, antitumor, antimicrobial, estrogenic,
      antiestrogenic, antioxidant, mutagenic and antimutagenic) targeting different
      pathways. Some of these compounds such as Genistein, Daidzein or its synthetic
      derivative Phenoxodiol as well as Luteolin and Quercetin are able to inhibit DNA
      topoisomerases. This review discusses that Flavonoids targeting DNA
      topoisomerases may lead to novel drug development with anticancer potential.

PMID- 22998569
TI  - Structure-activity relationship studies on clinically relevant HIV-1 NNRTIs.
AB  - In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease
      inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse
      transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment
      of HIV-1 infections. More than 60 structurally different classes of compounds
      have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse
      transcriptase (RT). Five NNRTIs (nevirapine, delavirdine, efavirenz, etravirine
      and rilpivirine) have been approved by US Food and Drug Administration (FDA) for
      clinical use. The NNRTIs bind with a specific 'pocket' site of HIV-1 RT
      (allosteric site) that is closely associated with the NRTI binding site. Due to
      mutations of the amino acid residues surrounding the NNRTI-binding site, NNRTIs
      are notorious for rapidly eliciting resistance. Though, the emergence of
      resistant HIV strains can be circumvented if the NNRTIs are used either alone or
      in combination with NRTIs (AZT, 3TC, ddI, ddC, TVD or d4T) and PIs (Indinavir,
      nelfinavir, saquinavir, ritonavir and lopinavir etc.) as shown by both a decrease
      in plasma HIV-1 RNA levels and increased CD4 T-cells. Here we are going to
      discuss recent advances in structure activity relationship studies on nevirapine,
      delavirdine, efavirenz, etravirine, rilpivirine and 4-thiazolidinones (privileged
      scaffold) HIV-1 NNRTIs.

PMID- 22998570
TI  - Physico-chemical properties mediating reproductive and developmental toxicity of
      engineered nanomaterials.
AB  - With the increasing production of engineered nanomaterials (ENMs) exploited in
      many consumer products, a wider number of people is expected to be exposed to
      such materials in the near future, both in occupational and environmental
      settings. This has raised concerns about the possible implications on public
      health. In particular, very recently the scientific community has focused on the
      effect that ENMs might exert on the reproductive apparatus and on embryonic
      development. Indications that ENMs might have adverse effects on cells of the
      germ line and on the developing embryos have been reported. In the present
      minireview we will perform a critical analysis of the published work on
      reproductive and developmental toxicity of the most commonly used nanoparticles
      with a major focus on mammalian models. We will place emphasis on the main
      physico-chemical characteristics that can affect NP behaviour in biological
      systems, i.e. presence of contaminants and nanoparticle destabilization, size,
      dosage, presence of functional groups, influence of the solvent used for their
      suspension in biological media, aggregation/agglomeration, intrinsic chemical
      composition and protein corona/opsonisation. The importance of this specific
      field of nanotoxicology is documented by the rapidly increasing number of
      published papers registered in the last three years, which might be a consequence
      of the growing concerns on the possible interference of ENMs with reproductive
      ability and pregnancy outcome, in a time in which reproductive age has increased
      and the possibility to bear children appears reduced.

PMID- 22998571
TI  - Implant-supporting telescopic maxillary prostheses and immediate loading.
AB  - Immediate loading (IL) in the maxilla is a successful concept when implants are
      splinted together using a fixed restoration. This concept is associated with high
      number of implants or difficulties in the plaque control underneath the
      restoration, which may reduce the patient comfort and satisfaction and compromise
      the implant prognosis. OBJECTIVE: The aim of this study was to evaluate the long
      term clinical outcome of implants placed in the maxilla using telescopic-retained
      removable prostheses under immediate functional loading protocol. MATERIAL AND
      METHODS: The present retrospective study included 117 implants with a progressive
      thread design placed in 26 patients (age 57.04 +/- 8.87 years old) with clinical
      and radiographic evaluation for a period of at least 2 years. A total of 29
      implants (24.79%) were placed in fresh extraction sockets. All implants were
      placed 1-3 mm subcrestally from the mid-facial crest of bone level. The implants
      were connected immediately after placement with conical prefabricated abutments
      (4- to 6-degree angle) using a final torque of 15 Ncm immediately after surgery.
      Secondary prefabricated copings with precise fit for the abutments were placed
      and the partial dentures were relined chair-side. The restorations were palate
      free and were to remain in place without removal for 10 days to splint the
      implants together. RESULTS: After a loading period of 54.42 +/- 15.68 months
      (min. 26 months/max. 87 months), the study showed 7 failures (5.98% failure
      rate), and 10 implants presented a crestal bone loss of more than 2 mm (8.55%).
      This represented a cumulative survival rate of 94.02% and a success rate for the
      evaluated implants of 85.47%. All patients were satisfied with the stability of
      their prostheses and no complications were reported. CONCLUSIONS: Telescopic
      implant-supported maxillary prostheses in conjunction with IL present an
      alternative prosthetic solution for the edentulous maxilla, providing long-term
      predictability and improving the patient comfort and clinical outcome.

PMID- 22998572
TI  - High incidence of skin cancer in the Channel Islands.
AB  - BACKGROUND: Previous studies looking at rates of malignant melanoma (MM) and
      nonmelanoma skin cancer (NMSC) in the UK have documented one of the highest rates
      in the southwest of England; however, the incidence of these tumours in Guernsey
      and Jersey, two of the Channel Islands, has not previously been reported. AIMS:
      To determine the incidence of cutaneous MM and NMSC in the Channel Islands.
      METHODS: Data for the period 2005-2009 were obtained from clinical and
      histopathological records for all MMs excised in the Channel Islands, and from
      the South-west Cancer Registry for MMs excised in the southwest of England and
      for NMSCs in both areas. The age-standardized incidence rate (ASRs) per 100,000
      of the population in the Channel Islands were compared with those with the
      southwest of England, the UK and the rest of Europe where available. The MM
      characteristics of the Channel Islands were then compared with the southwest of
      England using standardized incidence ratios (SIRs). RESULTS: The ASR/100,000 for
      cutaneous MM for 2005-2009 was 30 for the Channel Islands (31.3 for Jersey, 28.2
      for Guernsey), 20.3 for the southwest of England, and 15.6 for the UK. Comparison
      with the rest of Europe indicated that the incidence of MM in the Channel Islands
      is one of the highest in Europe. The highest incidence of MM was in the over 65
      years age group on both Guernsey and Jersey, and when divided into 5-year age
      bands, the 70-74 years age group had the highest rate. This suggests that this
      particular age group may have previously received greater exposure to some
      environmental factor that promotes MM development. The ASR/100,000 for NMSC was
      also higher for the Channel Islands (263.3) than for the southwest of England
      (174.6) for 2005-2009, and for the UK in 2009 (104.9). CONCLUSIONS: This study
      indicates that the Channel Islands have a high incidence of skin cancer (both MM
      and NMSC). In addition, the data show that the ASRs in older people in this
      population group differ from those in mainland UK, showing higher rates in the
      over 65 years age group.

PMID- 22998573
TI  - T cell immunoglobulin-3 as a new therapeutic target for rheumatoid arthritis.
AB  - T cell immunoglobulin-3 (Tim-3) is a surface molecule expressed on various cell
      types of the immune system which plays a central role in immune regulation.
      Recently, identification of galectin-9 (Gal-9) as a ligand for Tim-3 has
      established the Tim-3-Gal-9 pathway as an important regulator of Th1 immunity and
      induction of tolerance. The interaction of Tim-3 with Gal-9 induces cell death;
      the in vivo blockade of this interaction results in exacerbated autoimmunity and
      abrogation of tolerance in experimental models, thus establishing Tim-3 as a
      negative regulatory molecule. A number of previous studies have demonstrated that
      Tim-3 influences chronic autoimmune diseases, such as multiple sclerosis and
      systemic lupus erythematosus. In addition, an association between Tim-3
      polymorphisms and susceptibility to several autoimmune diseases has been
      identified in various autoimmune diseases, including rheumatoid arthritis (RA).
      Recent work has focused on the role of Tim-3 in RA, and the results indicate that
      Tim-3 may represent a novel target for the treatment of RA. In this article we
      will discuss the Tim-3 pathway and the therapeutic potential of modulating the
      Tim-3 pathway in RA.

PMID- 22998574
TI  - On the free radical scavenging activities of melatonin's metabolites, AFMK and
      AMK.
AB  - The reactions of N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK) and N(1) 
      acetyl-5-methoxykynuramine (AMK) with (*) OH, (*) OOH, and *OOCCl3 radicals have
      been studied using the density functional theory. Three mechanisms of reaction
      have been considered: radical adduct formation (RAF), hydrogen transfer (HT), and
      single electron transfer (SET). Their relative importance for the free radical
      scavenging activity of AFMK and AMK has been assessed. It was found that AFMK and
      AMK react with *OH at diffusion-limited rates, regardless of the polarity of the
      environment, which supports their excellent *OH radical scavenging activity. Both
      compounds were found to be also very efficient for scavenging *OOCCl3 , but
      rather ineffective for scavenging *OOH. Regarding their relative activity, it was
      found that AFMK systematically is a poorer scavenger than AMK and melatonin. In
      aqueous solution, AMK was found to react faster than melatonin with all the
      studied free radicals, while in nonpolar environments, the relative efficiency of
      AMK and melatonin as free radical scavengers depends on the radical with which
      they are reacting. Under such conditions, melatonin is predicted to be a better
      *OOH and *OOCCl3 scavenger than AMK, while AMK is predicted to be slightly better
      than melatonin for scavenging *OH. Accordingly it seems that melatonin and its
      metabolite AMK constitute an efficient team of scavengers able of deactivating a
      wide variety of reactive oxygen species, under different conditions. Thus, the
      presented results support the continuous protection exerted by melatonin, through
      the free radical scavenging cascade.

PMID- 22998575
TI  - Long duration of multiple system atrophy.

PMID- 22998576
TI  - Morphological and molecular characterization of a new myxozoan species
      (Myxosporea) infecting the gall bladder of Raja clavata (Chondrichthyes), from
      the Portuguese Atlantic Coast.
AB  - Microscopic and molecular procedures are used to describe a new myxosporean
      species, Chloromyxum clavatum n. sp., infecting the cartilaginous fish Raja
      clavata Linnaeus, 1758 (Chondrichthyes: Rajidae), collected from the northwest
      Atlantic coast of Portugal. Young plasmodia and mature spores were found floating
      free in the gall bladder of R. clavata . Spores were spherical to subspherical
      with a pointed anterior end, measuring14.4 +/- 0.5 MUm (n = 25) in length, 11.9
      +/- 0.5 MUm (n = 25) in width, and 9.4 +/- 0.5 MUm (n = 15) in thickness. The
      spore's wall was composed of 2 equally sized valves, each displaying 6-8 elevated
      surface ridges and a bundle of several tapering caudal filaments attached to the
      basal portion. Spores contained 4 pyriform equally sized polar capsules (5.5 +/-
      0.4 MUm * 2.9 +/- 0.5 MUm) (n = 25), each possessing an obliquely arranged
      isofilar polar filament coiled in 7-8 coils. Morphological data, host
      specificity, tissue tropism, and molecular analysis of the SSU rDNA gene identify
      this parasite as a new species of Chloromyxum. Neighbor-joining and maximum
      likelihood further reveal the parasite clustering with other species of
      Chloromyxum infecting the gall bladder of marine cartilaginous fish to form a
      clade positioned at the base of the freshwater clade, therefore constituting an
      exception to the major division of the class Myxosporea into the freshwater and
      marine clades, while supporting the existence of a correlation between tissue
      tropism and myxosporean phylogeny.

PMID- 22998577
TI  - New family of cerium halide based materials: CeX3.ROH compounds containing
      planes, chains, and tetradecanuclear rings.
AB  - Six members of a new family of cerium-halide-based materials with promising
      scintillation behavior have been synthesized in single crystal form, and their
      crystal structures were determined. Specifically, these new compounds are
      [(CeCl(3))(7)(BuOH)(16)(H(2)O)(2)].(BuOH)(2) (1), (CeBr(3))(14)(BuOH)(36) (2),
      [(CeCl(3))(7)(1-PrOH)(16)(H(2)O)(2)].(1-PrOH)(2) (3), [(CeBr(3))(7)(1
      PrOH)(18)].(1-PrOH)(2) (4), [(CeCl(3))(6)(iBuOH)(15)].(iBuOH)(2) (5), and
      CeCl(3)(sec-BuOH)(2)(H(2)O) (6). Additionally, the scintillation ability of
      compound 1 was established. The structures of these cerium-halide-based materials
      consist of catenated tetradecanuclear rings that arrange themselves into three
      distinct structural motifs which contain the largest lanthanide-based ring
      structures reported to date; the different motifs are obtained by involving
      specific alcohols during synthesis. Specifically, n-butanol and n-propanol lead
      to 1-D chains of tetradecanuclear rings, and iso-butanol leads to 2-D parquet
      patterned sheets of rectangular tetradecanuclear rings, while sec-butanol results
      in a zigzag 1-D chain structure. One of the compounds,
      [(CeCl(3))(6)(iBuOH)(15)].(iBuOH)(2), has been shown to scintillate with a light
      yield of up to 1920 photons/MeV, and due to the presence of protons, it should be
      capable of detecting high energy neutrons without the necessity of prior
      thermalization. Furthermore, it also appears to be the first cerium-based
      compound that scintillates in spite of the fact that water coordinates to two of
      the Ce(III) centers within the structure.

PMID- 22998578
TI  - Quantitative 3D evaluation of step ascent and descent in individuals with Down
      syndrome--analysis of a daily challenging task.
AB  - BACKGROUND: Step ascent and descent can perturb stability increasing the
      incidence of falls, especially in older individuals with functional limitations
      and intellectual disabilities, such as those with Down syndrome (DS). The aim of
      this study was to investigate the biomechanics and motor coordination of step
      ascent and descent in adults with DS and compare them with a group of healthy
      individuals, considering movement kinematics and kinetics. METHOD: Fourteen
      adults with DS and 12 similarly aged adults without DS who were free of known
      motor problems were quantitatively assessed during ascending and descending a
      step using an optoelectronic system (BTS SMART-D), force platforms and video
      recording. Kinematic and kinetic parameters were identified and calculated for
      each study participant and comparisons were made between the DS and a control
      group (CG). RESULTS: Despite similar age ranges, subjects in the DS group
      performed the step ascent and descent movements slower, with longer duration and
      with a more accentuated range of motion of the trunk and of the ankle joint than
      those in the CG. Additionally, the double stance phase on the step was
      substantially longer in the DS group when represented as a percentage of the
      entire stepping sequence (ascent, double stance on the step and descent). In
      terms of kinetics, ground force platform data revealed that the DS subjects
      showed higher instability in the medio-lateral direction during double support
      phase than similarly aged CG subjects and cannot be attributed to age-associated
      changes in stability. CONCLUSIONS: These findings help to elucidate the complex
      biomechanical strategy of people with DS during a step ascent and descent
      movement task and may have a major role in the multidimensional evaluation and
      tailored management for them.

PMID- 22998580
TI  - A review of the effects of moisturisers on the appearance of scars and striae.
AB  - Scars are well known to have a stratum corneum that is malfunctional. Increases
      in transepidermal water loss and decreases in stratum corneum capacitance and
      conductance have been reported. Occlusion therapy is a well-known route to
      improving the signs and symptoms of scarring. Until recently that has been
      assumed to be totally pressure related. However, studies have demonstrated that
      the direct effects of hydration on keratinocytes and fibroblasts contribute to
      the reduction in hypertrophic scarring. Now it is well known that occlusion can
      regulate epidermal cytokine and growth factor production; changes in profibrotic
      and antifibrotic factors have been established. As a result it is to be expected
      that moisturisers may improve the signs and symptoms of scars. As striae have
      been suggested to be anatomically similar to scars and since it is well
      established that paracrine signalling occurs in skin it is expected that striae
      have similar stratum corneum issues. While one cannot exclude the effects of some
      of the ingredients used in the products, several studies are reported in this
      review which demonstrates that moisturisation is a key component to reducing the
      clinical signs and symptoms of scars and striae. This is a good example of how
      knowledge of corneobiology leads to corneotherapies for these skin condition
      problems. The paper is being written in memory of Professor Johann Wiechers who,
      before he died tragically in November 2011, performed two of the reported studies
      together with colleagues. (c) 2012 Society of Cosmetic Scientists and the Societe
      Francaise de Cosmetologie.

PMID- 22998579
TI  - Analysis of TIR- and non-TIR-NBS-LRR disease resistance gene analogous in pepper:
      characterization, genetic variation, functional divergence and expression
      patterns.
AB  - BACKGROUND: Pepper (Capsicum annuum L.) is one of the most important vegetable
      crops worldwide. However, its yield and fruit quality can be severely threatened
      by several pathogens. The plant nucleotide-binding site (NBS)-leucine-rich repeat
      (LRR) gene family is the largest class of known disease resistance genes (R
      genes) effective against such pathogens. Therefore, the isolation and
      identification of such R gene homologues from pepper will provide a critical
      foundation for improving disease resistance breeding programs. RESULTS: A total
      of 78 R gene analogues (CaRGAs) were identified in pepper by degenerate PCR
      amplification and database mining. Phylogenetic tree analysis of the deduced
      amino acid sequences for 51 of these CaRGAs with typically conserved motifs ( P
      loop, kinase-2 and GLPL) along with some known R genes from Arabidopsis and
      tomato grouped these CaRGAs into the non-Toll interleukin-1 receptor (TIR)-NBS
      LRR (CaRGAs I to IV) and TIR-NBS-LRR (CaRGAs V to VII) subfamilies. The presence
      of consensus motifs (i.e. P-loop, kinase-2 and hydrophobic domain) is typical of
      the non-TIR- and TIR-NBS-LRR gene subfamilies. This finding further supports the
      view that both subfamilies are widely distributed in dicot species. Functional
      divergence analysis provided strong statistical evidence of altered selective
      constraints during protein evolution between the two subfamilies. Thirteen
      critical amino acid sites involved in this divergence were also identified using
      DIVERGE version 2 software. Analyses of non-synonymous and synonymous
      substitutions per site showed that purifying selection can play a critical role
      in the evolutionary processes of non-TIR- and TIR-NBS-LRR RGAs in pepper. In
      addition, four specificity-determining positions were predicted to be responsible
      for functional specificity. qRT-PCR analysis showed that both salicylic and
      abscisic acids induce the expression of CaRGA genes, suggesting that they may
      primarily be involved in defence responses by activating signaling pathways.
      CONCLUSION: The identified CaRGAs are a valuable resource for discovering R genes
      and developing RGA molecular markers for genetic map construction. They will also
      be useful for improving disease resistance in pepper. The findings of this study
      provide a better understanding of the evolutionary mechanisms that drive the
      functional diversification of non-TIR- and TIR-NBS-LRR R genes in pepper.

PMID- 22998581
TI  - Is mandibular reconstruction using vascularized fibula flaps and dental implants
      a reasonable treatment?
AB  - PURPOSE: this study retrospectively analyzed the rate of screwed implant
      insertion and risk factors in patients undergoing mandibular reconstruction with
      microsurgical revascularized fibula flaps. METHODS: This study retrospectively
      analyzed all patients with microvascularized fibula grafts between 1997 and 2005.
      Collected data included general data and risk factors (e.g., smoking, alcohol
      use), and irradiation was the main predictor variable. The number of patients
      rehabilitated with dental implants and the implant success rate were evaluated,
      possible influencing factors were identified, and the results were compared with
      previously published data. RESULTS: The sample included 33 patients (17 men, 16
      women; mean age: 52 years); 76% were smokers, 42% drank alcohol regularly, and
      73% had undergone mandible irradiation. Twenty-three patients received 140 screw
      retained implants for dental rehabilitation. Twenty-three implants were lost.
      Overall 1- and 5-year implant survival rates were 94% and 83%, respectively.
      Implant survival rates were 86% in non-irradiated mandibular bone, 86% in non
      irradiated grafted fibular bone, 82% in irradiated mandibular bone, and 38% in
      irradiated grafted fibular bone. CONCLUSION: This study showed that the use of
      dental implants in patients with fibula flaps is an appropriate and successful
      option for dental rehabilitation, even in those with risk factors such as
      smoking, alcohol use, and irradiation. Implant placement in irradiated grafted
      bone seems to be a high-risk procedure.

PMID- 22998582
TI  - Improving international research with clinical specimens: 5 achievable
      objectives.
AB  - Our increased interest in translational research has created a large demand for
      blood, tissue, and other clinical samples, which find use in a broad variety of
      research including genomics, proteomics, and metabolomics. Hundreds of millions
      of dollars have been invested internationally on the collection, storage, and
      distribution of samples. Nevertheless, many researchers complain in frustration
      about their inability to obtain relevant and/or useful samples for their
      research. Lack of access to samples, poor condition of samples, and
      unavailability of appropriate control samples have slowed our progress in the
      study of diseases and biomarkers. In this perspective, I focus on five major
      challenges that thwart clinical sample use for translational research and propose
      near term objectives to address them. They include: (1) defining our biobanking
      needs; (2) increasing the use of and access to standard operating procedures; (3)
      mapping interobserver differences for use in normalizing diagnoses; (4)
      identifying natural internal protein controls; and (5) redefining the clinical
      sample paradigm by building partnerships with the public. In each case, I believe
      that we have the tools at hand required to achieve the objective within 5 years.
      Potential paths to achieve these objectives are explored. However we solve these
      problems, the future of proteomics depends on access to high quality clinical
      samples, collected under standardized conditions, accurately annotated and shared
      under conditions that promote the research we need to do.

PMID- 22998583
TI  - Anaplastic lymphoma kinase as a therapeutic target.
AB  - INTRODUCTION: Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has
      been initially identified through its involvement in chromosomal translocations
      associated with anaplastic large cell lymphoma. However, recent evidence that
      aberrant ALK activity is also involved in an expanding number of tumor types,
      such as other lymphomas, inflammatory myofibroblastic tumor, neuroblastomas and
      some carcinomas, including non-small cell lung carcinomas, is boosting research
      progress in ALK-targeted therapies. AREAS COVERED: The first aim of this review
      is to describe current understandings about the ALK tyrosine kinase and its
      implication in the oncogenesis of human cancers as a fusion protein or through
      mutations. The second goal is to discuss its interest as a therapeutic target and
      to provide a review of the literature regarding ALK inhibitors. Mechanisms of
      acquired resistance are also reviewed. EXPERT OPINION: Several ALK inhibitors
      have recently been developed, offering new treatment options in tumors driven by
      abnormal ALK signaling. However, as observed with other tyrosine kinase
      inhibitors, resistance has emerged in patients treated with these agents. The
      complexity of mechanisms of acquired resistance recently described suggests that
      other therapeutic options, including combination of ALK and other kinases
      targeted drugs, will be required in the future.

PMID- 22998586
TI  - Addition of beta-lactoglobulin produces water-soluble shikonin.
AB  - Shikonin and its ester derivatives belong to a group of secondary metabolites
      with a wide array of beneficial effects on human health. However, shikonin is
      principally used in oil-based preparations due to the low solubility of the
      pigment in aqueous media, and the positive properties of shikonin are not
      exploited to their full potential. Such low aqueous solubility often results in
      poor bioavailability, makes shikonin undesirable for oral administration, and
      restricts its broadened use in the food and pharmaceutical industries. The
      purpose of this study was to enhance the aqueous solubility of shikonin by the
      addition of beta-lactoglobulin and to characterize the macromolecule-ligand
      binding interaction by means of spectrophotometry, spectrofluorometry, high
      performance liquid chromatography, and mass spectrometry. In the presence of beta
      lactoglobulin the solubility of shikonin is increased up to 181-fold. One
      shikonin molecule binds covalently to beta-lactoglobulin via Cys(121), whereas
      the remaining pigment molecules most probably bind to the protein via noncovalent
      interactions.

PMID- 22998585
TI  - Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria
      promotes genomic instability and altered DNA damage response.
AB  - Epidemiological evidence links chronic bacterial infections to the increased
      incidence of certain types of cancer but the molecular mechanisms by which
      bacteria contribute to tumour initiation and progression are still poorly
      characterized. Here we show that chronic exposure to the genotoxin cytolethal
      distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and
      acquisition of phenotypic properties of malignancy in fibroblasts and colon
      epithelial cells. Cells grown for more than 30 weeks in the presence of sublethal
      doses of CDT showed increased mutation frequency, and accumulation of chromatin
      and chromosomal aberrations in the absence of significant alterations of cell
      cycle distribution, decreased viability or senescence. Cell survival was
      dependent on sustained activity of the p38 MAP kinase. The ongoing genomic
      instability was associated with impaired activation of the DNA damage response
      and failure to efficiently activate cell cycle checkpoints upon exposure to
      genotoxic stress. Independently selected sublines showed enhanced anchorage
      independent growth as assessed by the formation of colonies in semisolid agarose.
      These findings support the notion that chronic infection by CDT-producing
      bacteria may promote malignant transformation, and point to the impairment of
      cellular control mechanisms associated with the detection and repair of DNA
      damage as critical events in the process.

PMID- 22998587
TI  - Molecular cloning of rice serotonin N-acetyltransferase, the penultimate gene in
      plant melatonin biosynthesis.
AB  - Because of the absence of an arylalkylamine N-acetyltransferase (AANAT) homolog
      in the plant genome, the proposal was made that a GCN5-related N
      acetyltransferase superfamily gene (GNAT) could be substituted for AANAT. To
      clone rice serotonin N-acetyltransferase (SNAT), we expressed 31 rice GNAT cDNAs
      in Escherichia coli and screened SNAT activity by measuring N-acetyltryptamine
      after application with 1 mm tryptamine. GNAT5 was shown to produce high levels of
      N-acetyltryptamine in E. coli, suggesting a possible rice SNAT. To confirm SNAT
      activity, the GNAT5 protein was purified through affinity purification from E.
      coli culture. The purified recombinant GNAT5 showed high SNAT enzyme activity
      catalyzing serotonin into N-acetylserotonin. The values for Km and Vmax were 385
      MUm and 282 pmol/min/mg protein, respectively. An in vitro enzyme assay of
      purified SNAT showed N-acetylserotonin formation to be proportional to enzyme
      concentration and time, with peak activity at pH 8.8. High substrate
      concentrations above 1 mm serotonin inhibited SNAT activity. Finally, the mRNA
      level of SNAT was higher in shoots than in roots, but it was expressed
      constitutively, unlike N-acetylserotonin methyltransferase (ASMT), the terminal
      enzyme in melatonin synthesis. These results suggest that ASMT rather than SNAT
      is the rate-limiting enzyme of melatonin biosynthesis in plants. 

PMID- 22998588
TI  - Pt5Gd as a highly active and stable catalyst for oxygen electroreduction.
AB  - The activity and stability of Pt(5)Gd for the oxygen reduction reaction (ORR)
      have been studied, using a combination of electrochemical measurements, angle
      resolved X-ray photoelectron spectroscopy (AR-XPS), and density functional theory
      calculations. Sputter-cleaned, polycrystalline Pt(5)Gd shows a 5-fold increase in
      ORR activity, relative to pure Pt at 0.9 V, approaching the most active in the
      literature for catalysts prepared in this way. AR-XPS profiles after
      electrochemical measurements in 0.1 M HClO(4) show the formation of a thick Pt
      overlayer on the bulk Pt(5)Gd, and the enhanced ORR activity can be explained by
      means of compressive strain effects. Furthermore, these novel bimetallic
      electrocatalysts are highly stable, which, in combination with their enhanced
      activity, makes them very promising for the development of new cathode catalysts
      for fuel cells.

PMID- 22998590
TI  - New dicyano cyclometalated compounds containing Pd(II)-Tl(I) bonds as building
      blocks in 2D extended structures: synthesis, structure, and luminescence studies.
AB  - New mixed metal complexes [PdTl(C^N)(CN)(2)] [C^N = 7,8-benzoquinolinate (bzq,
      3); 2-phenylpyridinate (ppy, 4)] have been synthesized by reaction of their
      corresponding precursors (NBu(4))[Pd(C^N)(CN)(2)] [C^N = bzq (1), ppy (2)] with
      TlPF(6). Compounds 3 and 4 were studied by X-ray diffraction, showing the not-so
      common Pd(II)-Tl(I) bonds. Both crystal structures exhibit 2-D extended networks
      fashioned by organometallic "PdTl(C^N)(CN)(2)" units, each one containing a donor
      acceptor Pd(II)-Tl(I) bond, which are connected through additional Tl...N=C
      contacts and weak Tl...pi (bzq) contacts in the case of 3. Solid state emissions
      are red-shifted compared with those of the precursors and have been assigned to
      metal-metal'-to-ligand charge transfer (MM'LCT [d/s sigma*(Pd,Tl) -> pi*(C^N)])
      mixed with some intraligand ((3)IL[pi(C^N) -> pi*(C^N)]) character. In diluted
      solution either at room temperature or 77 K, the Pd-Tl bond is no longer retained
      as confirmed by mass spectrometry, NMR, and UV-vis spectroscopic techniques.

PMID- 22998589
TI  - Thromboprophylaxis prescribing and thrombotic event rates in multiple myeloma
      patients treated with lenalidomide or thalidomide at a specialist cancer
      hospital.
AB  - AIM: To assess thromboprophylaxis prescribing patterns against current guidelines
      and report thromboembolism (TE) incidence in multiple myeloma (MM) patients
      treated with thalidomide (thal) or lenalidomide (len) at a specialist cancer
      hospital over a one-year period. METHOD: Dispensing records of thal and len,
      diagnosis of MM, patients' characteristics, disease status, co-prescribed
      medicines including thromboprophylaxis and incidence of TE were extracted from
      patients' records and a patient survey conducted to identify patients who sourced
      thromboprophylactic medicines outside the hospital. RESULTS: Enoxaparin was most
      the commonly prescribed thromboprophylactic agent (43%), followed by low-dose
      aspirin (26%) and therapeutic warfarin (6%). The thromboprophylactic strategy
      (including no prophylaxis) could not be determined for 22% of patients. TE
      incidence (with any thromboprophylaxis) was 9.3 and 9.1% in thal-based and len
      based regimens, respectively. CONCLUSION: Both aspirin and enoxaparin
      thromboprophylaxis were prescribed for patients on both low-risk and high-risk
      immunomodulatory drug-based regimens, deviating from current consensus
      guidelines. Treatment of comorbidities constituted the rationale for maintenance
      on therapeutic warfarin. Fixed low-dose warfarin was not prescribed. TE event
      rates (with any thromboprophylaxis) were consistent with those reported in the
      literature. Documentation of a chosen strategy was lacking for nearly a quarter
      of patients, resulting in uncertainty of treatment plan for other members of the
      multidisciplinary treating team. Centers need to work towards evidence-based
      institutional guidelines and improving documentation practices for
      thromboprophylaxis in their MM patients.

PMID- 22998591
TI  - Total synthesis of acortatarin A using a Pd(II)-catalyzed spiroketalization
      strategy.
AB  - The total synthesis of acortatarin A relying on a Pd(II)-catalyzed
      spiroketalization is reported. This strategy allows a single stereocenter in the
      spiroketalization substrate to produce the target efficiently under mild
      conditions, installing the necessary oxygenation in the backbone through an
      allylic transposition. The synthesis also verifies that pollenopyrroside B and
      acortatarin A are the same compound, and electrochemical studies suggest that the
      reported bioactivity is not due to simple antioxidant properties.

PMID- 22998592
TI  - Patients' aggressive behaviours towards nurses: development and psychometric
      properties of the hospital aggressive behaviour scale- users.
AB  - AIM: This article is to report the development and psychometric testing of the
      Hospital Aggressive Behaviour Scale - Users. BACKGROUND: Workplace violence is
      present in many work spheres, but in the healthcare sector, nurses in particular
      are at more risk due to the close contact they maintain with users and clients
      and the special characteristics of this relationship. DESIGN: Using qualitative
      and quantitative methodology, an instrument was applied to a sample of 1,489
      nurses from 11 public hospitals. Data collection was carried out in 2010 and
      2011. RESULTS: Exploratory factor analysis yielded a 10-item instrument
      distributed in two factors (non-physical violence and physical violence), which
      was validated by means of confirmatory factor analysis. Both the resulting
      questionnaire and the factors identified present high internal consistency and
      adequate external validity, analysed by means of statistically significant
      correlations between the Hospital Aggressive Behaviour Scale and job
      satisfaction, burnout components, and psychological well-being. CONCLUSIONS: The
      results indicate that, in nursing personnel, higher exposure to user violence
      leads to lower job satisfaction, more emotional exhaustion and more cynicism, and
      to a lower level of psychological well-being. The instrument developed in this
      study may be very useful in the sphere of assessment and prevention of
      psychosocial risks for the early detection of the problem of user violence in its
      two facets.

PMID- 22998593
TI  - Cu(II) Schiff base as catalyst in the synthesis of 1,8-dioxodecahydroacridine.
AB  - The catalytic property of Cu(II) Schiff-base complex in an efficient synthesis of
      1,8-dioxodecahydroacridines was investigated. The one-pot three component
      reaction of dimedone, aromatic aldehydes and aromatic amines or ammonium acetate
      in water afforded the corresponding 1,8-dioxodecahydroacridines with excellent
      yields. This reaction was carried out in the presence of 1 mol% of catalysts at
      room temperature. The reusability of the catalysts was demonstrated by a five-run
      test without loss of its activity. Also, this catalyst possesses several
      advantages including mild reaction conditions, lower catalytic loading, shorter
      reaction times, high yield of the products, inexpensive and cleaner (Green
      chemistry) reactions.

PMID- 22998594
TI  - Predictors of self-injurious behaviour exhibited by individuals with autism
      spectrum disorder.
AB  - BACKGROUND: Presence of an autism spectrum disorder is a risk factor for
      development of self-injurious behaviour (SIB) exhibited by individuals with
      developmental disorders. The most salient SIB risk factors historically studied
      within developmental disorders are level of intellectual disability,
      communication deficits and presence of specific genetic disorders. Recent SIB
      research has expanded the search for risk factors to include less commonly
      studied variables for people with developmental disorders: negative affect,
      hyperactivity and impulsivity. METHOD: A heterogeneous sample of 617 individuals
      with autism spectrum disorder diagnoses was derived from the National Database of
      Autism Research. Latent constructs were estimated from items of the community
      version of the Aberrant Behaviour Checklist. Structural equation modelling was
      used to assess whether impulsivity, hyperactivity, negative affect, severity of
      stereotypy, intellectual functioning or severity of autism symptoms predicted
      severity of SIB. RESULTS: Impulsivity (beta = 0.46), followed by intellectual
      functioning (beta = -0.39), and stereotypy (beta = 0.23) were the variables most
      highly predictive of increased SIB; impulsivity and stereotypy remained
      significant predictors of SIB after severity of autism symptoms and intelligence
      quotient (IQ) were controlled for. CONCLUSIONS: High levels of impulsivity and
      stereotypy were significant predictors of SIB in a large and diverse sample of
      people with confirmed autism diagnoses. Future research is needed on the effects
      of reducing impulsivity and stereotypy on the outcomes of treatment, early
      intervention and attempts to prevent the development of SIB.

PMID- 22998595
TI  - Hypoxic enhancement of exosome release by breast cancer cells.
AB  - BACKGROUND: Exosomes are nanovesicles secreted by tumour cells which have roles
      in paracrine signalling during tumour progression, including tumour-stromal
      interactions, activation of proliferative pathways and bestowing
      immunosuppression. Hypoxia is an important feature of solid tumours which
      promotes tumour progression, angiogenesis and metastasis, potentially through
      exosome-mediated signalling. METHODS: Breast cancer cell lines were cultured
      under either moderate (1% O2) or severe (0.1% O2) hypoxia. Exosomes were isolated
      from conditioned media and quantitated by nanoparticle tracking analysis (NTA)
      and immunoblotting for the exosomal protein CD63 in order to assess the impact of
      hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by
      real-time reverse transcription polymerase chain reaction and normalised to
      exogenous and endogenous control genes. Statistical significance was determined
      using the Student T test with a P value of < 0.05 considered significant.
      RESULTS: Exposure of three different breast cancer cell lines to moderate (1% O2)
      and severe (0.1% O2) hypoxia resulted in significant increases in the number of
      exosomes present in the conditioned media as determined by NTA and CD63
      immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a
      hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant
      increase in exosome release. Transfection of cells with HIF-1alpha siRNA prior to
      hypoxic exposure prevented the enhancement of exosome release by hypoxia. The
      hypoxically regulated miR-210 was identified to be present at elevated levels in
      hypoxic exosome fractions. CONCLUSIONS: These data provide evidence that hypoxia
      promotes the release of exosomes by breast cancer cells, and that this hypoxic
      response may be mediated by HIF-1alpha. Given an emerging role for tumour cell
      derived exosomes in tumour progression, this has significant implications for
      understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may
      release more exosomes into their microenvironment to promote their own survival
      and invasion.

PMID- 22998597
TI  - Raphael Rubin, 1956-2011.

PMID- 22998596
TI  - High volume local anesthesia as a postoperative factor of pain and swelling in
      dental implants.
AB  - OBJECTIVE: To determine whether the administration of high-volume local
      anesthesia can influence postoperative pain and swelling, and the degree of
      patient satisfaction, following dental implant placement. MATERIAL AND METHODS:
      One hundred patients (45 women and 55 men) between 19 and 80 years old were
      divided into two groups: group A (n = 50, with placement of an implant using an
      atraumatic approach in each patient, with sub-periosteal injection of a volume of
      Ultracain((r)) <=0.9 mL [half a carpule]) and group B (n = 50, involving the same
      surgical procedure but infiltrating a local anesthetic volume of >=7.2 mL [four
      carpules]). Visual analog scales were used in all patients to rate intraoperative
      pain and postoperative pain and swelling. After the first week, the patients
      completed a questionnaire evaluating satisfaction with treatment. RESULTS: The
      intraoperative pain scores were similar in both groups (p = 0.363), while the
      postoperative pain and swelling scores were significantly lower in group A at all
      time points. Patient rated satisfaction with the surgical treatment was higher in
      group A. CONCLUSIONS: Excess injected volume of local anesthetic in dental
      implant surgery has a negative impact upon both postoperative pain and swelling,
      and on patient rated satisfaction.

PMID- 22998598
TI  - Relevance of multiple basin drainage and primary histologic regression in
      prognosis of trunk melanoma patients with negative sentinel lymph nodes.
AB  - BACKGROUND: Lymphatic drainage to multiple basins (MLBD) is frequently observed
      in patients with primary melanoma located in the trunk. Conflicting data
      regarding the prognostic impact of MLBD are reported. OBJECTIVE AND METHODS: We
      reviewed our case series of 352 patients with trunk melanoma to evaluate the
      pattern of basin drainage and to analyse whether different basin drainages may
      have different significance in negative sentinel lymph node (SLN) patients. The
      presence of single/multiple basin drainage, the status of SLN, the presence of
      melanoma regression, Breslow thickness, ulceration and type of melanoma were
      recorded for each patients and correlated to Disease Free Survival (DFS) and
      Overall Survival (OS). RESULTS: MLBD occurred in 77 patients (21.9%) and single
      basin lymphatic drainage (SLBD) occurred in 275 patients (79.1%). The presence of
      metastases in SLN was not significantly different in patients with MLBD compared
      to those with SLBD (26% vs. 19.6%). No differences in OS and DFS were found in
      SLBD/MLBD independently from SLN status. However DFS was higher in patients with
      MLBD and negative SLN (P = 0.0001), in addition, in patients with negative SLN
      and SLBD disease recurrence was 19% while was only 7% in patients with negative
      SLN obtained from MLBD (P = 0.03). Multivariate analysis showed that Breslow
      thickness <2 mm, MLBD pattern and regression of melanoma were favourable
      variables for DFS of patients with negative SLN. CONCLUSIONS: An accurate study
      of the drainage basin and of all the SLNs obtained from MLBD is recommended
      because of the impact in prognosis of melanoma of the trunk.

PMID- 22998599
TI  - Neurocognition in youth and young adults under age 30 at familial risk for
      schizophrenia: a quantitative and qualitative review.
AB  - INTRODUCTION: Neurocognitive dysfunction is a central feature of schizophrenia
      and is observed during all phases of the illness. Because schizophrenia is known
      to run in families, studying neurocognitive function in first-degree,
      nonpsychotic relatives has been a widely utilised strategy for almost 50 years
      for understanding presumed "genetic risk". Studying nonpsychotic relatives
      ("familial high-risk", or FHR) allows for identification of cognitive
      vulnerability markers independent of confounds associated with psychosis.
      METHODS: Prior meta-analyses have elucidated the level and pattern of cognitive
      deficits in the premorbid, prodromal, and postonset periods of psychosis, and in
      relatives regardless of age. However, no prior quantitative analyses have
      specifically focused on studies of young first-degree relatives of individuals
      with schizophrenia who have not passed through the peak age illness risk (<age
      30). The English language literature of neuropsychological studies of first
      degree relatives for schizophrenia was identified up to 15 May 2011. RESULTS:
      From 33 studies, 28 studies met our criteria for quantitative review, utilising
      >70 individual tests and 250 variables. CONCLUSIONS: In general, young FHR
      individuals demonstrated deficits with a moderate level of severity compared with
      healthy controls. The largest average effect sizes (ESs), based on tests given in
      at least three independent studies, were on estimates of Full Scale IQ (d= 
      0.777), followed by Vocabulary (d= -0.749) and single word reading tests (d= 
      0.698) (often used as estimates of IQ). Measures of declarative memory, sustained
      attention, working memory and others had more modest ESs. Deficits were milder
      than in established schizophrenia, but often as severe as in clinical high-risk
      or putatively prodromal participants and in older relatives examined in prior
      meta-analyses. Additionally, while assessed from a more limited literature, youth
      at FHR for schizophrenia tended to show worse neurocognitive functioning than
      those at FHR for affective psychosis. This suggests that genetic risk for
      schizophrenia as reflected in a positive FHR carries an especially heavy impact
      on cognitive ability.

PMID- 22998600
TI  - High-resolution genotyping and mapping of recombination and gene conversion in
      the protozoan Theileria parva using whole genome sequencing.
AB  - BACKGROUND: Theileria parva is a tick-borne protozoan parasite, which causes East
      Coast Fever, a disease of cattle in sub-Saharan Africa. Like Plasmodium
      falciparum, the parasite undergoes a transient diploid life-cycle stage in the
      gut of the arthropod vector, which involves an obligate sexual cycle. As assessed
      using low-resolution VNTR markers, the crossover (CO) rate in T. parva is
      relatively high and has been reported to vary across different regions of the
      genome; non-crossovers (NCOs) and CO-associated gene conversions have not yet
      been characterised due to the lack of informative markers. To examine all
      recombination events at high marker resolution, we sequenced the haploid genomes
      of two parental strains, and two recombinant clones derived from ticks fed on
      cattle that had been simultaneously co-infected with two different parasite
      isolates. RESULTS: By comparing the genome sequences, we were able to genotype
      over 64 thousand SNP markers with an average spacing of 127 bp in the two progeny
      clones. Previously unrecognized COs in sub-telomeric regions were detected. About
      50% of CO breakpoints were accompanied by gene conversion events. Such a high
      fraction of COs accompanied by gene conversions demonstrated the contributions of
      meiotic recombination to the diversity and evolutionary success of T. parva, as
      the process not only redistributed existing genetic variations, but also altered
      allelic frequencies. Compared to COs, NCOs were more frequently observed and more
      uniformly distributed across the genome. In both progeny clones, genomic regions
      with more SNP markers had a reduced frequency of COs or NCOs, suggesting that the
      sequence divergence between the parental strains was high enough to adversely
      affect recombination frequencies. Intra-species polymorphism analysis identified
      81 loci as likely to be under selection in the sequenced genomes. CONCLUSIONS:
      Using whole genome sequencing of two recombinant clones and their parents, we
      generated maps of COs, NCOs, and CO-associated gene conversion events for T.
      parva. The data comprises one of the highest-resolution genome-wide analyses of
      the multiple outcomes of meiotic recombination for this pathogen. The study also
      demonstrates the usefulness of high throughput sequencing typing for detailed
      analysis of recombination in organisms in which conventional genetic analysis is
      technically difficult.

PMID- 22998601
TI  - Okara promoted acrylamide and carboxymethyl-lysine formation in bakery products.
AB  - Soybeans are widely used in bakery products because of their technological
      advantages and, recently, soybean-containing products have been marketed as
      functional foods thanks to several health benefits. Okara is a soybean-based
      ingredient obtained after elimination of the water-soluble component from ground
      soybeans. In this paper the effect of okara addition to bakery products on the
      formation of some potentially harmful Maillard reaction products was evaluated.
      Cookies obtained by replacing 15% of wheat flour with okara showed a visible
      browning increase and a more intense Maillard reaction development as shown by
      higher concentrations of 5-hydroxymethyl-2-furaldehyde (HMF) (+100%), acrylamide
      (+60%), and carboxymethyl-lysine (CML) (+400%) with respect to the control. This
      phenomenon could be related to the presence in okara of about 50% of insoluble
      dietary fiber: the fiber reduces water activity during cooking, thus promoting
      Maillard reaction. To confirm this hypothesis, cookies obtained by replacing 7%
      of wheat flour with three different types of dietary fiber (cellulose, chitosan,
      and pea fiber) were prepared: these experimental cookies showed higher Maillard
      reaction product concentration with respect to the control and, in particular,
      HMF and CML values were directly related to the fiber water-holding capacity
      (WHC). To extend the observation to the food market, a sampling of soybean
      containing commercial bakery products was analyzed by comparing the
      concentrations of Maillard reaction products with those of similar bakery
      products without soy. Soybean-containing samples showed higher concentrations of
      acrylamide and CML than corresponding controls. 

PMID- 22998603
TI  - Synthesis and structure of dirhodium analogue of octaborane-12 and decaborane-14.
AB  - We present the results of our investigation of a thermally driven cluster
      expansion of rhodaborane systems with BH(3).THF. Four novel rhodaborane clusters,
      for example, nido-[(Cp*Rh)(2)B(6)H(10)], 1; nido-[(Cp*Rh)B(9)H(13)], 2; nido
      [(Cp*Rh)(2)B(8)H(12)], 3; and nido-[(Cp*Rh)(3)B(8)H(9)(OH)(3)], 4 (Cp* = eta(5)
      C(5)Me(5)), have been isolated from the thermolysis of [Cp*RhCl(2)](2) and borane
      reagents in modest yields. Rhodaborane 1 has a nido geometry and is isostructural
      with [B(8)H(12)]. The low temperature (11)B and (1)H NMR data demonstrate that
      compound 1 exists in two isomeric forms. The framework geometry of 2 and 3 is
      similar to that of [B(10)H(14)] with one BH group in 2 (3-position), and two BH
      groups in 3 (3, 4-positions) are replaced by an isolobal {Cp*Rh} fragment. The 11
      vertex cluster 4 has a nido structure based on the 12 vertex icosahedron, having
      three rhodium and eight boron atoms. In addition, the reaction of rhodaborane 1
      with [Fe(2)(CO)(9)] yielded a condensed cluster
      [(Cp*Rh)(2){Fe(CO)(3)}(2)B(6)H(10)], 5. The geometry of 5 consists of [Fe(2)B(2)]
      tetrahedron and an open structure of [(Cp*Rh)(2)B(6)], fused through two boron
      atoms. The accuracy of these results in each case is established experimentally
      by spectroscopic characterization in solution and structure determinations in the
      solid state.

PMID- 22998602
TI  - Therapeutic targeting of the p53 pathway in cancer stem cells.
AB  - INTRODUCTION: Cancer stem cells (CSCs) are a high profile drug target for cancer
      therapeutics due to their indispensable role in cancer progression, maintenance
      and therapeutic resistance. Restoring wild-type (WT) p53 function is an
      attractive new therapeutic approach for the treatment of cancer due to the well
      described powerful tumor suppressor function of p53. As emerging evidence
      intimately links p53 and stem cell biology, this approach also provides an
      opportunity to target CSCs. AREAS COVERED: This review covers the therapeutic
      approaches to restore the function of WT p53, cancer and normal stem cell biology
      in relation to p53 and the downstream effects of p53 on CSCs. EXPERT OPINION: The
      restoration of WT p53 function by targeting p53 directly, its interacting
      proteins or its family members holds promise as a new class of cancer therapies.
      This review examines the impact that such therapies may have on normal and CSCs
      based on the current evidence linking p53 signaling with these populations.

PMID- 22998605
TI  - Molecular insights into bacteroid development during Rhizobium-legume symbiosis.
AB  - Rhizobial soil bacteria can form a symbiosis with legumes in which the bacteria
      fix atmospheric nitrogen into ammonia that can be utilized by the host. The
      plant, in turn, supplies the rhizobia with a carbon source. After infecting the
      host cell, the bacteria differentiate into a distinct bacteroid form, which is
      able to fix nitrogen. The bacterial BacA protein is essential for bacteroid
      differentiation in legumes producing nodule-specific cysteine-rich peptides
      (NCRs), which induce the terminal differentiation of the bacteria into
      bacteroids. NCRs are antimicrobial peptides similar to mammalian defensins, which
      are important for the eukaryotic response to invading pathogens. The BacA protein
      is essential for rhizobia to survive the NCR peptide challenge. Similarities in
      the lifestyle of intracellular pathogenic bacteria suggest that host factors
      might also be important for inducing chronic infections associated with Brucella
      abortus and Mycobacterium tuberculosis. Moreover, rhizobial lipopolysaccharide is
      modified with an unusual fatty acid, which plays an important role in protecting
      the bacteria from environmental stresses. Mutants defective in the biosynthesis
      of this fatty acid display bacteroid development defects within the nodule. In
      this review, we will focus on these key components, which affect rhizobial
      bacteroid development and survival.

PMID- 22998604
TI  - Evidence of lifestyle modification in the management of hypercholesterolemia.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of morbidity and
      mortality worldwide. The growth of ageing populations in developing countries
      with progressively urbanized lifestyles are major contributors. The key risk
      factors for CHD such as hypercholesterolemia, diabetes mellitus, and obesity are
      likely to increase in the future. These risk factors are modifiable through
      lifestyle. OBJECTIVES: To review current literature on the potential benefit of
      cholesterol lowering in CHD risk reduction with a particular focus on the
      evidence of non-pharmacological/lifestyle management of hypercholesterolemia.
      METHODS: Medline/PubMed systematic search was conducted using a two-tier approach
      limited to all recent English language papers. Primary search was conducted using
      key words and phrases and all abstracts were subsequently screened and relevant
      papers were selected. The next tier of searching was conducted by (1) reviewing
      the citation lists of the selected papers and (2) by using PubMed weblink for
      related papers. Over 3600 reports were reviewed. RESULTS: Target cholesterol
      levels set out in various guidelines could be achieved by lifestyle changes,
      including diet, weight reduction, and increased physical activity with the goal
      of reducing total cholesterol to <200 mg/dL and LDL-C<100 mg/dL. Various dietary
      constituents such as green tea, plant sterols, soy protein have important
      influences on total cholesterol. Medical intervention should be reserved for
      those patients who have not reached this goal after 3 months of non
      pharmacological approach. CONCLUSION: CHD remains as a leading cause of death
      worldwide and hypercholesterolemia is an important cause of CHD. Non
      pharmacological methods provide initial as well as long-term measures to address
      this issue.

PMID- 22998606
TI  - Prevention of influenza among travellers attending at a UK travel clinic: beliefs
      and perceptions. A cross-sectional study.
AB  - BACKGROUND: Travellers' compliance with measures to prevent influenza through the
      use of antivirals and influenza vaccine remains very poor despite influenza being
      one of the commonest travel and vaccine-preventable diseases. A study was
      undertaken to assess travellers' beliefs, perceptions and intentions to take
      antivirals for the treatment and prevention of influenza during the H1N1
      pandemic. METHODS: A cross-sectional survey (n = 96) of travellers who attended
      the Royal Free Travel Health Centre, London, UK was undertaken in September 2009.
      A self-administered questionnaire was completed by a traveller in advance of
      their pre-travel health consultation. Logistic regression identified variables
      independently associated with compliance. RESULTS: Influenza vaccination uptake
      for the 5 years preceding the study was found to be 20.8%. This was statistically
      significantly higher for older travellers and those with underlying health
      conditions (P < 0.005). Mean intention to comply with antiviral drugs on a
      preventive and therapeutic basis was 58% and 72%, respectively, and this varied
      markedly with age and with dispensed antimalarial chemoprophylaxis. CONCLUSION:
      This study identifies some beliefs and perceptions travellers consider with
      regard to the therapeutic and preventive influenza use of antivirals during the
      H1N1 pandemic; it underscores the importance of travellers receiving hemisphere
      appropriate influenza vaccination. The external validity of these study findings
      requires further corroboration involving other travel clinics and different
      cohorts of travellers during seasonal activity or outbreaks of influenza. These
      findings could guide the development of future strategies for the prevention of
      influenza in travellers.

PMID- 22998607
TI  - Comparison of dkgB-linked intergenic sequence ribotyping to DNA microarray
      hybridization for assigning serotype to Salmonella enterica.
AB  - Two DNA-based methods were compared for the ability to assign serotype to 139
      isolates of Salmonella enterica ssp. I. Intergenic sequence ribotyping (ISR)
      evaluated single nucleotide polymorphisms occurring in a 5S ribosomal gene region
      and flanking sequences bordering the gene dkgB. A DNA microarray hybridization
      method that assessed the presence and the absence of sets of genes was the second
      method. Serotype was assigned for 128 (92.1%) of submissions by the two DNA
      methods. ISR detected mixtures of serotypes within single colonies and it cost
      substantially less than Kauffmann-White serotyping and DNA microarray
      hybridization. Decreasing the cost of serotyping S. enterica while maintaining
      reliability may encourage routine testing and research.

PMID- 22998608
TI  - A systematic investigation into the nature of tryptic HCD spectra.
AB  - Modern mass spectrometry-based proteomics can produce millions of peptide
      fragmentation spectra, which are automatically identified in databases using
      sequence-specific b- or y-ions. Proteomics projects have mainly been performed
      with low resolution collision-induced dissociation (CID) in ion traps and beam
      type fragmentation on triple quadrupole and QTOF instruments. Recently, the
      latter has also become available with Orbitrap instrumentation as higher energy
      collisional dissociation (HCD), routinely providing full mass range fragmentation
      with high mass accuracy. To systematically study the nature of HCD spectra, we
      made use of a large scale data set of tryptic peptides identified with an FDR of
      0.0001, from which we extract a subset of more than 16,000 that have little or no
      contribution from cofragmented precursors. We employed a newly developed computer
      assisted "Expert System", which distills our experience and literature knowledge
      about fragmentation pathways. It aims to automatically annotate the peaks in high
      mass accuracy fragment spectra while strictly controlling the false discovery
      rate. Using this Expert System we determined that sequence specific regular ions
      covering the entire sequence were present for almost all peptides with up to 10
      amino acids (median 100%). Peptides up to 20 amino acid length contained
      sufficient fragmentation to cover 80% of the sequence. Internal fragments are
      common in HCD spectra but not in high resolution CID spectra (10% vs 1%). The low
      mass region contains abundant immonium ions (6% of fragment ion intensity), the
      characteristic a(2), b(2) ion pair (72% of spectra), side chain fragments and
      reporter ions for peptide modifications such as tyrosine phosphorylation. B- and
      y-ions account for only 20% of fragment ions by number but 53% by ion intensity.
      Overall, 84% of the fragment ion intensity was unambiguously explainable. Thus
      high mass accuracy HCD and CID data are near comprehensively and automatically
      interpretable.

PMID- 22998609
TI  - Enteric-coated mycophenolate sodium in psoriasis vulgaris: an open pilot study.
AB  - BACKGROUND: Mycophenolate mofetil is a well-known immunosuppressive agent in
      transplantation medicine. The efficacy of enteric-coated mycophenolate sodium (EC
      MPS) was confirmed in other inflammatory skin diseases, including atopic
      dermatitis and SCLE. OBJECTIVE: To investigate the efficacy and the
      tolerability/short-term safety of EC-MPS in patients with moderate to severe
      chronic plaque psoriasis. PATIENTS AND METHODS: An open-label pilot study in
      which 20 patients with a PASI >10 received EC-MPS 720 mg twice daily for 6 weeks
      followed by 360 mg twice daily for another 6 weeks. Patients who completed 12
      weeks of treatment were followed-up for an additional 12 weeks. Treatment
      outcomes were assessed with PASI50% and PASI75%. RESULTS: Eighteen men and two
      women (mean age 46 years) entered the study. Sixty-five percent (13/20) finished
      the treatment period. By week 6, no patient achieved PASI 75% and 8/20 patients
      achieved a PASI 50%. Compared to week 6, 4/13 showed a deterioration of their
      psoriasis at week 12. Twenty-five percent (2/8) achieved a PASI 75% in week 24.
      The most-reported adverse events were itching (30%), diarrhea (10%), and a
      reversible elevation of the triglycerides level. CONCLUSION: EC-MPS does not seem
      effective as monotherapy for moderate to severe psoriasis, but might be used at a
      dosage of 1440 mg daily in well-selected patients with treatment-resistant
      psoriasis.

PMID- 22998611
TI  - Efficient medium ring size bromolactonization using a sulfur-based zwitterionic
      organocatalyst.
AB  - Catalytic bromolactonization of long-chain olefinic acids resulting in the
      efficient synthesis of medium-sized lactones is reported using a zwitterionic
      catalyst and stoichiometric N-bromosuccinimide halogen source. The reaction was
      found to be more efficient at 0  degrees C than at room temperature, which could
      be attributed to the temperature dependence of the zwitterionic catalyst.

PMID- 22998610
TI  - Fe-catalyzed one-pot synthesis of 1,3-di- and 1,3,5-trisubstituted pyrazoles from
      hydrazones and vicinal diols.
AB  - An iron-catalyzed route for the regioselective synthesis of 1,3- and 1,3,5
      substituted pyrazoles from the reaction of diarylhydrazones and vicinal diols has
      been developed. This method was found to be practical with wide substrate scope.

PMID- 22998612
TI  - Access to eye health services among indigenous Australians: an area level
      analysis.
AB  - BACKGROUND: This project is a community-level study of equity of access to eye
      health services for Indigenous Australians. METHODS: The project used data on eye
      health services from multiple sources including Medicare Australia, inpatient and
      outpatient data and the National Indigenous Eye Health Survey.The analysis
      focused on the extent to which access to eye health services varied at an area
      level according to the proportion of the population that was Indigenous (very low
      = 0-1.0%, low = 1.1-3.0%, low medium = 3.1-6.0%, high medium = 6.1-10.0%, high =
      10.1-20.0%, very high = 20 + %). The analysis of health service utilisation also
      took into account age, remoteness and the Socioeconomic Indices for Areas
      (SEIFA). RESULTS: The rate of eye exams provided in areas with very high
      Indigenous populations was two-thirds of the rate of eye exams for areas with
      very low indigenous populations. The cataract surgery rates in areas with high
      medium to very high Indigenous populations were less than half that reference
      areas. In over a third of communities with very high Indigenous populations the
      cataract surgery rate fell below the World Health Organization (WHO) guidelines
      compared to a cataract surgery rate of 3% in areas with very low Indigenous
      populations. CONCLUSIONS: There remain serious disparities in access to eye
      health service in areas with high Indigenous populations. Addressing disparities
      requires a co-ordinated approach to improving Indigenous people's access to eye
      health services. More extensive take-up of existing Medicare provisions is an
      important step in this process. Along with improving access to health services,
      community education concerning the importance of eye health and the effectiveness
      of treatment might reduce reluctance to seek help.

PMID- 22998613
TI  - Alien and endangered plants in the Brazilian Cerrado exhibit contrasting
      relationships with vegetation biomass and N : P stoichiometry.
AB  - Although endangered and alien invasive plants are commonly assumed to persist
      under different environmental conditions, surprisingly few studies have
      investigated whether this is the case. We examined how endangered and alien
      species are distributed in relation to community biomass and N : P ratio in the
      above-ground community biomass in savanna vegetation in the Brazilian Cerrado.
      For 60 plots, we related the occurrence of endangered (Red List) and alien
      invasive species to plant species richness, vegetation biomass and N : P ratio,
      and soil variables. Endangered plants occurred mainly in plots with relatively
      low above-ground biomass and high N : P ratios, whereas alien invasive species
      occurred in plots with intermediate to high biomass and low N : P ratios.
      Occurrences of endangered or alien plants were unrelated to extractable N and P
      concentrations in the soil. These contrasting distributions in the Cerrado imply
      that alien species only pose a threat to endangered species if they are able to
      invade sites occupied by these species and increase the above-ground biomass
      and/or decrease the N : P ratio of the vegetation. We found some evidence that
      alien species do increase above-ground community biomass in the Cerrado, but
      their possible effect on N : P stoichiometry requires further study.

PMID- 22998614
TI  - Cardiovascular risk in the young type 1 diabetes population with a low 10-year,
      but high lifetime risk of cardiovascular disease.
AB  - Diabetes mellitus is associated with excess cardiovascular mortality that is
      evident in all age groups, but is most pronounced in young people with type 1
      diabetes. Cardiovascular risk estimation models generally estimate the
      probability of future events over a 10-year time horizon. Due to the dependency
      on age, children and adolescents with type 1 diabetes would be considered at low
      short-term risk but high life-time risk of developing a cardiovascular event.
      Guidelines recommend screening particularly for microvascular complications
      including nephropathy and retinopathy beginning around puberty. Identification of
      early microvascular abnormalities in children and adolescents not only predict
      later development of long-term microvascular complications and further end-organ
      damage but are associated with an increased risk for future macrovascular events.
      This may be because of the fact that the same glycaemic mechanisms responsible
      for the occurrence of microvascular disease may also apply to the development of
      atherosclerosis. Alternatively, interventions that reduce the development of
      microvascular end-organ damage may also delay the development of associated
      macrovascular disease. Screening for subclinical atherosclerosis, especially in
      the coronary and carotid vessels, has been advocated as a means of detecting
      early atherosclerotic disease in asymptomatic individuals with the aim of
      potentially reclassifying cardiovascular risk and guiding therapeutic
      interventions. Currently there is no randomized clinical trial evidence that
      additional screening using non-invasive imaging techniques alters cardiovascular
      disease outcomes. We do not know the best approach or combination of approaches
      to assess risk and reduce cardiovascular disease burden in type 1 diabetes
      mellitus. All screening interventions carry harms as well as benefits and until
      further evidence becomes available additional screening using non-invasive
      imaging tests for the detection of subclinical atherosclerosis cannot be
      currently recommended for patients with type 1 diabetes.

PMID- 22998615
TI  - Dating and substance use in adolescent peer networks: a replication and
      extension.
AB  - AIMS: The current report examined associations between romantic partner, peer and
      individual substance use behaviors in a sample of American adolescents. DESIGN:
      The report used two waves of data (8th and 9th grades) from the Partnerships to
      Enhance Resilience (PROSPER) intervention project and focused on dating couples
      and their friends in 54 sampled school-cohorts. Hierarchical logistic regression
      models examined the associations between friend, partner and friend-of-partner
      substance use and daters' future drinking and smoking. SETTING: Surveys
      administered in rural Pennsylvania and Iowa secondary schools. PARTICIPANTS: A
      total of 744 dating couples. MEASUREMENTS: Student participants completed
      questionnaires that assessed substance use, background characteristics and dating
      and friend nominations. Friend, partner and friend-of-partner substance use were
      assessed at each wave directly from respective reports. FINDINGS: Consistent with
      a bridging hypothesis, friends-of-partner drinking had a strong and independent
      association with subsequent drunkenness (b = 1.40, P < 0.01) and drinking (b =
      0.82, P < 0.01) among daters, and these associations did not vary by gender. A
      similar association was not observed for smoking, where partner (b = 0.77, P <
      0.01) and direct friends (b = 1.19, P < 0.05) smoking showed strong and
      significant associations with future smoking, but friends-of-partner smoking did
      not (b = -0.44, P > 0.10). CONCLUSION: Romantic partner and peer behaviors have
      substantially different associations with adolescent drinking and smoking.
      Intervention efforts aimed at reducing teenage smoking should be aimed at
      proximal peer and romantic relationships, whereas interventions of teenage
      drinking should also include the wider circle of indirect friends.

PMID- 22998616
TI  - A prospective randomized study on the immediate loading of mandibular
      overdentures supported by one or two implants; a 3 year follow-up report.
AB  - AIM: The objective of the study was to evaluate and compare treatments with
      mandibular overdentures supported by one or two immediately placed implants 3
      years after loading. MATERIALS AND METHODS: Thirty-six edentulous subjects were
      eligible for inclusion. Using a random sampling system, one or two implants were
      placed in the mandible. Separate ball attachments were connected to the implants,
      and the denture was relined and delivered the day of surgery with the retentive
      components incorporated in the denture base. At the follow-up examinations peri
      implant bone levels, implant and denture stability/retention, and need for
      maintenance and adjustments were evaluated. Moreover, the OHIP-EDENT
      questionnaire was used to measure patient satisfaction. RESULTS: Nineteen
      subjects (10 men and 9 women) with a mean age of 56 years were available for the
      3-year follow-up examination. The group with 1 implant (Group 1) consisted of 11
      subjects (5 women and 6 men) while the remaining 8 (5 women and 3 men) belonged
      to Group2. Nine subjects had been excluded during the first year due to failing
      implants, 6 had moved, 1 had died, and 1 reported severe illness. No implant
      failures between the 12-and 36 month follow-up were observed. The mean peri
      implant bone change was.86 mm and the Implant Stability Quotient showed only
      minor changes with no significant difference between the groups when compared
      with the 12-month follow-up. Patient satisfaction scores increased significantly
      when compared with the baseline values and continued to be high for both groups
      and need for denture maintenance was low. CONCLUSION: No significant differences
      were found between subjects in the two groups with respect to implant survival
      and peri implant bone loss, and patient satisfaction scores continued to be high
      for both groups. Need for denture maintenance was low in both groups.

PMID- 22998617
TI  - Pt(II)-mediated imine-nitrile coupling leading to symmetrical (1,3,5,7,9
      pentaazanona-1,3,6,8-tetraenato)Pt(II) complexes containing the incorporated 1,3
      diiminoisoindoline moiety.
AB  - Treatment of trans-[PtCl(2)(NCR)(2)] (1; R = Et (1a), Ph (1b)) with 1,3
      diiminoisoindoline (2) gives access to the corresponding symmetrical (1,3,5,7,9
      pentaazanona-1,3,6,8-tetraenato)Pt(II) complexes
      [PtCl{NH?C(R)N?C(C(6)H(4))NC?NC(R)?NH}] (3). The reactions of 1 with one
      equivalent of 1,1,3,3-tetramethylguanidine (4), 1,3-diphenylguanidine (6), or
      acetone oxime (8) leads to the formation of mixed asymmetrical Pt(II) complexes
      trans-[PtCl(2){NH?C(R)N?C(NMe(2))(2)}(NCR)] (5), [PtCl{NH?C(R)NC(NHPh)?NPh}(NCR)]
      (7), or trans-[PtCl(2){NH?C(Ph)ON?CMe(2)}(NCPh)] (9), respectively, as a result
      of nucleophilic addition to one of the nitrile ligands in 1. Treatment of 5, 7,
      and 9 with one equivalent of 2 leads to complexes 3. The complexes were
      characterized by IR, (1)H, (13)C{(1)H}, and (195)Pt NMR (for 3) spectroscopies,
      ESI(+)-MS, elemental analyses, and X-ray diffraction (for 3). Complex 3a has an
      asymmetric unit with five independent Pt molecules of the same chemical
      composition and two molecules of water, resulting in a total of 40 molecules of
      the complex and sixteen guest water molecules per unit cell. Theoretical
      calculations revealed that the most plausible mechanism of formation of complexes
      3 includes stepwise nucleophilic addition of 2 to one of the nitrile ligands in
      1, a first cyclization upon formation of the Pt-N bond and elimination of HCl,
      and a second nucleophilic addition/cyclization.

PMID- 22998618
TI  - A study of redundancy and neutrality in evolutionary optimization.
AB  - Some authors consider that evolutionary search may be positively influenced by
      the use of redundant representations, whereas others note that the addition of
      random redundancy to a representation could be useless in optimization. Given
      this lack of consensus, two new families of redundant binary representations are
      developed in this paper. The first family is based on linear transformations and
      is considered non-neutral. The second family of representations is designed to
      implement neutrality, and is based on the mathematical formulation of error
      control codes. A study aimed at assessing the influence of redundancy and
      neutrality on the performance of a simple evolutionary hillclimber is presented.
      The (1+1)-ES is modeled using Markov chains and is applied to NK fitness
      landscapes. The results indicate that the phenotypic neighborhood induced by a
      redundant representation dominates the behavior of the algorithm, affecting the
      search more strongly than neutrality, and the representations with better
      performance on NK fitness landscapes do not exhibit extreme values of any of the
      indicators of representation quality commonly adopted in the literature. 

PMID- 22998619
TI  - Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms
      of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in
      Spain (1994-2006).
AB  - BACKGROUND: Group A Streptococcus (GAS) causes human diseases ranging in severity
      from uncomplicated pharyngitis to life-threatening necrotizing fasciitis and
      shows high rates of macrolide resistance in several countries. Our goal is to
      identify antimicrobial resistance in Spanish GAS isolates collected between 1994
      and 2006 and to determine the molecular epidemiology (emm/T typing and PFGE) and
      resistance mechanisms of those resistant to erythromycin and tetracycline.
      RESULTS: Two hundred ninety-five out of 898 isolates (32.8%) were erythromycin
      resistant, with the predominance of emm4T4, emm75T25, and emm28T28, accounting
      the 67.1% of the 21 emm/T types. Spread of emm4T4, emm75T25 and emm28T28
      resistant clones caused high rates of macrolide resistance. The distribution of
      the phenotypes was M (76.9%), cMLSB (20.3%), iMLSB (2.7%) with the involvement of
      the erythromycin resistance genes mef(A) (89.5%), msr(D) (81.7%), erm(B) (37.3%)
      and erm(A) (35.9%).Sixty-one isolates were tetracycline resistant, with the main
      representation of the emm77T28 among 20 emm/T types. To note, the combination of
      tet(M) and tet(O) tetracycline resistance genes were similar to tet(M) alone
      reaching values close to 40%. Resistance to both antibiotics was detected in 19
      isolates of 7 emm/T types, being emm11T11 and the cMLSB phenotype the most
      frequent ones. erm(B) and tet(M) were present in almost all the strains, while
      erm(A), mef(A), msr(D) and tet(O) appeared in less than half of them.
      CONCLUSIONS: Spanish GAS were highly resistant to macrolides meanwhile showed
      minor resistance rate to tetracycline. A remarkable correlation between
      antimicrobial resistance and emm/T type was noticed. Clonal spread of emm4T4,
      emm75T25 and emm28T28 was the main responsable for macrolide resistance where as
      that emm77T28 clones were it to tetraclycline resistance. A wide variety of
      macrolide resistance genes were responsible for three macrolide resistance
      phenotypes.

PMID- 22998620
TI  - Purification and characterization of Ara h1 and Ara h3 from four peanut market
      types revealed higher order oligomeric structures.
AB  - This study aimed to purify and characterize the peanut allergens Ara h1 and Ara
      h3 from four cultivars that represent the four major market types to provide
      better understanding of the molecular organization of oligomers in different
      market types. The chromatographic profiles of Ara h1 and Ara h3 from the four
      cultivars obtained from anion exchange chromatography were similar. However, they
      differed in the distribution of trimeric and hexameric structures of Ara h3
      isolated by size exclusion chromatography. The Menzies (Runner market type) and
      Walter (Spanish market type) cultivars, wherein Ara h3 proteins consist of two
      acidic subunits, exhibited trimeric and hexameric conformations proportionally.
      However, the Middleton (Virginia market type) and Kelinci (Valencia market type)
      cultivars, wherein Ara h3 proteins consist of three acidic subunits, showed
      predominantly a hexameric structure. The oligomeric structures of the purified
      Ara h1 demonstrated strong IgE binding properties, whereas the allergenic
      property of the oligomeric Ara h3 could not be performed due to lack of
      availability of specific IgE. In addition, the polyclonal antibodies raised
      against the purified Ara h1 and Ara h3 showed highly specific binding to their
      respective antigens.

PMID- 22998621
TI  - Mechanism of action of methamphetamine within the catecholamine and serotonin
      areas of the central nervous system.
AB  - Addiction to methamphetamine (METH) is thought to be mediated by dopaminergic
      effects in the reward pathway in the brain via the A10 dopaminergic pathway.
      Herein we describe an overview of the results of the basic preclinical science
      undertaken to provide mechanistic insights into the action of amphetamines in
      general and METH in particular. A brief history of amphetamine and METH use and
      abuse is given, and an overview of the relevant chemical aspects of amphetamine
      as they relate to neurotransmitters in general is made. A review of the methods
      used to study the biochemical effects of METH is outlined. Finally, a focused
      analysis of the kinetic mechanisms of action of the amphetamines in general, and
      METH in particular, at the transmembrane transporters and at the intracellular
      vesicular storage sites is made. A description of how catecholaminergic and
      serotonergic nerve signaling may be altered by METH is proposed. Overall, the
      emphasis here is on differences in effects observed between the striatal (the A9
      substantia nigral dopamine pathway) and nucleus accumbens (the A10, ventral
      tegmental pathway) areas of the brain following acute as well as repeated dosing
      and withdrawal.

PMID- 22998623
TI  - Ethanol extract of peanut sprout induces Nrf2 activation and expression of
      antioxidant and detoxifying enzymes in human dermal fibroblasts: implication for
      its protection against UVB-irradiated oxidative stress.
AB  - A peanut sprout is known to contain a significant level of resveratrol, which was
      reported to have beneficial effects in our body due to its antioxidant
      activities. The purpose of this study was to evaluate the cytoprotective activity
      of ethanol extract of peanut sprout (EPS) from ultraviolet B (UVB)-induced
      oxidative stress in human dermal fibroblasts (HDF). EPS was revealed to contain
      54.2 MUg g(-1) of trans-resveratrol. The DCF-DA-positive reactive oxygen species
      level was increased by 50 mJ cm(-2) of UVB irradiation (2150 +/- 450% of
      nonirradiated control), which was markedly suppressed by EPS treatment (180 +/-
      42% of control). Annexin V-positive apoptotic cell death induced by UVB
      irradiation (16.4 +/- 4.5%) was also significantly inhibited by EPS treatment
      (6.7 +/- 2.5%). EPS induced up-regulation and nuclear translocation of Nrf2, a
      transcription factor for antioxidant and detoxifying enzymes, in HDF as a dose
      dependent manner. UVB irradiation up-regulated Nrf2-dependent enzymes of heme
      oxygenase-1, NAD(P)H:quinine oxidoreductase-1 and glutathione-S-transferase pi,
      and they were further stimulated by EPS treatment. Taken together, EPS is an
      efficient cytoprotective agent against UVB-induced oxidative stress by activation
      of Nrf2 and upregulation of Nrf2-relating antioxidant and detoxifying enzymes in
      HDF.

PMID- 22998622
TI  - Advances in the development of universal influenza vaccines.
AB  - Despite the widespread availability and use of influenza vaccines, influenza
      still poses a considerable threat to public health. Vaccines against seasonal
      influenza do not offer protection against pandemic viruses, and vaccine efficacy
      against seasonal viruses is reduced in seasons when the vaccine composition is
      not a good match for the predominant circulating viruses. Vaccine efficacy is
      also reduced in older adults, who are one of the main target groups for
      vaccination. The continual threat of pandemic influenza, with the known potential
      for rapid spread around the world and high mortality rates, has prompted
      researchers to develop a number of novel approaches to providing immunity to this
      virus, focusing on target antigens which are highly conserved between different
      influenza A virus subtypes. Several of these have now been taken into clinical
      development, and this review discusses the progress that has been made, as well
      as considering the requirements for licensing these new vaccines and how they
      might be used in the future.

PMID- 22998624
TI  - Serological survey of viral hepatitis markers among newly diagnosed patients with
      HIV/AIDS in China.
AB  - OBJECTIVES: The aim of the study was to determine the seroprevalence and
      epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infection among patients newly diagnosed with HIV/AIDS in China. METHODS: Two
      thousand and forty patients newly diagnosed with HIV/AIDS from 10 provinces in
      China were selected during 2009 to 2010. Serum samples obtained from each
      individual were screened for HBV and HCV serum markers [HBV surface antigen
      (HBsAg), HBV surface antibody (HBsAb), HBV envelope antigen (HBeAg), HBV envelope
      antibody (HBeAb), HBV core antibody (HBcAb) and HCV antibody (HCVAb)]; liver
      function tests were also performed. Demographics and medical histories were
      collected. RESULTS: Of the 2040 patients, 741 (36.3%) were positive for at least
      one HBV and HCV serum marker; 300 (14.71%) were HCVAb positive, and 248 (12.16%)
      were isolated HCVAb positive; 222 (10.9%) were positive for HBsAg; 19 (0.93%)
      were positive for both HBsAg and HCVAb. The highest prevalence of HBsAg
      positivity was found in Guangxi (15.31%), followed by Guangdong (15.19%) and
      Shanghai (14.36%). The highest prevalence of HCVAb positivity was found in
      Xinjiang (43.18%), followed by Henan (39.06%) and Yunnan (27.36%). The proportion
      of patients with abnormal liver function in patients positive for HCVAb and/or
      HBsAg was significantly higher than that in those who were negative for both
      HCVAb and HBsAg (P < 0.001). CONCLUSIONS: The seroprevalence of HBV and HCV among
      patients newly diagnosed with HIV/AIDS in China is high. HBsAg and HCVAb
      positivity prevalences were found to vary significantly in different provinces in
      China. Patients newly diagnosed with HIV/AIDS and coinfected with HBV and HCV are
      at higher risk of abnormal liver function. It is necessary to routinely screen
      for HBV and HCV infection among patients newly diagnosed with HIV/AIDS.

PMID- 22998625
TI  - Beware of proteins bearing gifts: protein antibiotics that use iron as a Trojan
      horse.
AB  - Multicellular organisms limit the availability of free iron to prevent the
      utilization of this essential nutrient by microbial pathogens. As such, bacterial
      pathogens possess a variety of mechanisms for obtaining iron from their hosts,
      including a number of examples of vertebrate pathogens that obtain iron directly
      from host proteins. Recently, two novel members of the colicin M bacteriocin
      family were discovered in Pectobacterium that suggest that this phytopathogen
      possesses such a system. These bacteriocins (pectocin M1 and M2) consist of a
      cytotoxic domain homologous to that of colicin M fused to a horizontally acquired
      plant-like ferredoxin. This ferredoxin domain substitutes the portion of colicin
      M required for receptor binding and translocation, presumably fulfilling this
      role by parasitizing an existing ferredoxin-based iron acquisition pathway. The
      ability of susceptible strains of Pectobacterium to utilize plant ferredoxin as
      an iron source was also demonstrated, providing additional evidence for the
      existence of such a system. If this hypothesis is correct, it represents the
      first example of iron piracy directly from a host protein by a phytopathogen and
      serves as a testament of the flexibility of evolution in creating new bacteriocin
      specificities.

PMID- 22998626
TI  - Shared decision making and behavioral impairment: a national study among children
      with special health care needs.
AB  - BACKGROUND: The Institute of Medicine has prioritized shared decision making
      (SDM), yet little is known about the impact of SDM over time on behavioral
      outcomes for children. This study examined the longitudinal association of SDM
      with behavioral impairment among children with special health care needs (CSHCN).
      METHOD: CSHCN aged 5-17 years in the 2002-2006 Medical Expenditure Panel Survey
      were followed for 2 years. The validated Columbia Impairment Scale measured
      impairment. SDM was measured with 7 items addressing the 4 components of SDM. The
      main exposures were (1) the mean level of SDM across the 2 study years and (2)
      the change in SDM over the 2 years. Using linear regression, we measured the
      association of SDM and behavioral impairment. RESULTS: Among 2,454 subjects
      representing 10.2 million CSHCN, SDM increased among 37% of the population,
      decreased among 36% and remained unchanged among 27%. For CSHCN impaired at
      baseline, the change in SDM was significant with each 1-point increase in SDM
      over time associated with a 2-point decrease in impairment (95% CI: 0.5, 3.4),
      whereas the mean level of SDM was not associated with impairment. In contrast,
      among those below the impairment threshold, the mean level of SDM was significant
      with each one point increase in the mean level of SDM associated with a 1.1-point
      decrease in impairment (0.4, 1.7), but the change was not associated with
      impairment. CONCLUSION: Although the change in SDM may be more important for
      children with behavioral impairment and the mean level over time for those below
      the impairment threshold, results suggest that both the change in SDM and the
      mean level may impact behavioral health for CSHCN.

PMID- 22998627
TI  - Cluster coordination and photoluminescence properties of alpha-Ag2WO4
      microcrystals.
AB  - In this paper, we report our initial research to obtain hexagonal rod-like
      elongated silver tungstate (alpha-Ag(2)WO(4)) microcrystals by different methods
      [sonochemistry (SC), coprecipitation (CP), and conventional hydrothermal (CH)]
      and to study their cluster coordination and optical properties. These
      microcrystals were structurally characterized by X-ray diffraction (XRD),
      Rietveld refinements, Fourier transform infrared (FT-IR), X-ray absorption near
      edge structure (XANES), and extended X-ray absorption fine structure (EXAFS)
      spectroscopies. The shape and average size of these alpha-Ag(2)WO(4)
      microcrystals were observed by field-emission scanning electron microscopy (FE
      SEM). The optical properties of these microcrystals were investigated by
      ultraviolet-visible (UV-vis) spectroscopy and photoluminescence (PL)
      measurements. XRD patterns and Rietveld refinement data confirmed that alpha
      Ag(2)WO(4) microcrystals have an orthorhombic structure. FT-IR spectra exhibited
      four IR-active modes in a range from 250 to 1000 cm(-1). XANES spectra at the W
      L(3)-edge showed distorted octahedral [WO(6)] clusters in the lattice, while
      EXAFS analyses confirmed that W atoms are coordinated by six O atoms. FE-SEM
      images suggest that the alpha-Ag(2)WO(4) microcrystals grow by aggregation and
      the Ostwald ripening process. PL properties of alpha-Ag(2)WO(4) microcrystals
      decrease with an increase in the optical band-gap values (3.19-3.23 eV). Finally,
      we observed that large hexagonal rod-like alpha-Ag(2)WO(4) microcrystals prepared
      by the SC method exhibited a major PL emission intensity relative to alpha
      Ag(2)WO(4) microcrystals prepared by the CP and CH methods.

PMID- 22998628
TI  - Transient non-native burial of a Trp residue occurs initially during the
      unfolding of a SH3 domain.
AB  - The detection and characterization of non-native interactions in a partially
      unfolded form of any protein are important not only with regard to how they might
      facilitate folding but also in the context of their possible role in driving the
      protein toward amyloid fibril formation. The SH3 domain of PI3 kinase is known to
      unfold via an early, partially unfolded intermediate. In this study, the kinetics
      of unfolding of this protein in guanidine hydrochloride was studied by monitoring
      the fluorescence of its sole tryptophan residue, W53. W53 is fully solvent
      exposed in both the native and unfolded states, as indicated by a similar
      wavelength (356-357 nm) of maximal fluorescence emission, and a similar quantum
      yield of fluorescence. W53 becomes partially buried in the unfolding
      intermediate, as seen in the 6-7 nm blue shift in its wavelength of maximal
      fluorescence emission in the intermediate, and in the transient initial increase
      in the quantum yield of its fluorescence during unfolding. It appears that W53 is
      engaged in non-native interactions in the unfolding intermediate. It is also
      shown that the transition from the native state to the unfolding intermediate
      occurs as a gradual and not an all-or-none transition.

PMID- 22998629
TI  - Steady-state levels of retinal 24S-hydroxycholesterol are maintained by glial
      cells intervention after elevation of intraocular pressure in the rat.
AB  - PURPOSE: Our previous studies suggested that CYP46A1 and 24S-hydroxycholesterol
      (24SOH) may be associated with glaucoma. Loss of CYP46A1-expressing retinal
      ganglion cells is involved in the activation of glia, and therefore possibly in
      the disbalance of cholesterol. In this context, the purpose of our present work
      was to emphasize the glial and longitudinal CYP46A1 expression after an
      interventional glaucoma-related stress triggered by elevated intraocular pressure
      (IOP). METHODS: Sprague-Dawley rats were submitted to laser photocoagulation of
      the trabecular meshwork, limbus and episcleral veins in one eye to induce
      elevated IOP. Rats were euthanized at days 3, 14, 30 and 60 (n = 10 per time
      point), and 24SOH was measured in plasma and retina by gas chromatography-mass
      spectrometry. CYP46A1 was quantified by Western blotting. Glial activation was
      assessed by glial fibrillary acidic protein immunoreactivity in Western blots and
      retinal cryosections. RESULTS: Sustained high IOP was observed in experimental
      eyes from day 1 to day 21. Plasma MCP-1 and ICAM-1, quantified using multiplex
      assay kits, were increased at day 3. Glial activation was observed bilaterally at
      all time-points, at lower levels in contralateral eyes than in experimental eyes.
      In experimental retinas, CYP46A1 expression showed a transient increase at day 3
      and then returned to baseline. Plasma and retinal 24SOH peaked at day 14 and 30,
      respectively. CONCLUSIONS: These data show that CYP46A1 expression was induced
      early in response to retinal stress but remained constant at late time-points,
      reinforcing the constitutive role of CYP46A1 in maintaining cholesterol balance
      in neuronal tissues.

PMID- 22998630
TI  - Identification and characterization of the echinocandin B biosynthetic gene
      cluster from Emericella rugulosa NRRL 11440.
AB  - Echinocandins are a family of fungal lipidated cyclic hexapeptide natural
      products. Due to their effectiveness as antifungal agents, three semisynthetic
      derivatives have been developed and approved for treatment of human invasive
      candidiasis. All six of the amino acid residues are hydroxylated, including 4R,5R
      dihydroxy-L-ornithine, 4R-hydroxyl-L-proline, 3S,4S-dihydroxy-L-homotyrosine, and
      3S-hydroxyl-4S-methyl-L-proline. We report here the biosynthetic gene cluster of
      echinocandin B 1 from Emericella rugulosa NRRL 11440 containing genes encoding
      for a six-module nonribosomal peptide synthetase EcdA, an acyl-AMP ligase EcdI,
      and oxygenases EcdG, EcdH, and EcdK. We showed EcdI activates linoleate as
      linoleyl-AMP and installs it on the first thiolation domain of EcdA. We have also
      established through ATP-PP(i) exchange assay that EcdA loads L-ornithine in the
      first module. A separate hty gene cluster encodes four enzymes for de novo
      generation of L-homotyrosine from acetyl-CoA and 4-hydroxyphenyl-pyruvate is
      found from the sequenced genome. Deletions in the ecdA, and htyA genes validate
      their essential roles in echinocandin B production. Five predicted iron-centered
      oxygenase genes, ecdG, ecdH, ecdK, htyE, and htyF, in the two separate ecd and
      hty clusters are likely to be the tailoring oxygenases for maturation of the
      nascent NRPS lipohexapeptidolactam product.

PMID- 22998631
TI  - Neural mechanisms of subclinical depressive symptoms in women: a pilot functional
      brain imaging study.
AB  - BACKGROUND: Studies of individuals who do not meet criteria for major depressive
      disorder (MDD) but with subclinical levels of depressive symptoms may aid in the
      identification of neurofunctional abnormalities that possibly precede and predict
      the development of MDD. The purpose of this study was to evaluate relations
      between subclinical levels of depressive symptoms and neural activation patterns
      during tasks previously shown to differentiate individuals with and without MDD.
      METHODS: Functional magnetic resonance imaging (fMRI) was used to assess neural
      activations during active emotion regulation, a resting state scan, and reward
      processing. Participants were twelve females with a range of depressive symptoms
      who did not meet criteria for MDD. RESULTS: Increased depressive symptom severity
      predicted (1) decreased left midfrontal gyrus activation during reappraisal of
      sad stimuli; (2) increased right midfrontal gyrus activation during distraction
      from sad stimuli; (3) increased functional connectivity between a precuneus seed
      region and left orbitofrontal cortex during a resting state scan; and (4)
      increased paracingulate activation during non-win outcomes during a reward
      processing task. CONCLUSIONS: These pilot data shed light on relations between
      subclinical levels of depressive symptoms in the absence of a formal MDD
      diagnosis and neural activation patterns. Future studies will be needed to test
      the utility of these activation patterns for predicting MDD onset in at-risk
      samples.

PMID- 22998632
TI  - Dimerization control in the self-assembly behavior of copillar[5]arenes bearing
      omega-hydroxyalkoxy groups.
AB  - Two novel copillar[5]arenes bearing omega-hydroxyalkoxy groups are synthesized
      and their self-assembly properties are studied by (1)H NMR spectroscopy, specific
      viscosity, and X-ray measurements. The copillar[5]arene 2b bearing a 6
      hydroxyhexyloxy group exhibits a reversible self-assembly behavior, leading to
      the formation of the self-inclusion monomer and hugging dimers. The reversible
      self-assembly behavior can be controlled by tuning solvent, temperature, guest,
      and H-bond interaction. However, the copillar[5]arene 2a bearing a short 4
      hydroxybutyloxy group does not show such a self-assembly behavior to the
      formation of the self-inclusion monomer and hugging dimers.

PMID- 22998633
TI  - Differential infection properties of three inducible prophages from an epidemic
      strain of Pseudomonas aeruginosa.
AB  - BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen
      infecting the lungs of patients with cystic fibrosis (CF). The Liverpool Epidemic
      Strain (LES) is transmissible, capable of superseding other P. aeruginosa
      populations and is associated with increased morbidity. Previously, multiple
      inducible prophages have been found to coexist in the LES chromosome and to
      constitute a major component of the accessory genome not found in other sequenced
      P. aerugionosa strains. LES phages confer a competitive advantage in a rat model
      of chronic lung infection and may, therefore underpin LES prevalence. Here the
      infective properties of three LES phages were characterised. RESULTS: This study
      focuses on three of the five active prophages (LESphi2, LESphi3 and LESphi4) that
      are members of the Siphoviridae. All were induced from LESB58 by norfloxacin.
      Lytic production of LESphi2 was considerably higher than that of LESphi3 and
      LESphi4. Each phage was capable of both lytic and lysogenic infection of the
      susceptible P. aeruginosa host, PAO1, producing phage-specific plaque
      morphologies. In the PAO1 host background, the LESphi2 prophage conferred
      immunity against LESphi3 infection and reduced susceptibility to LESphi4
      infection. Each prophage was less stable in the PAO1 chromosome with
      substantially higher rates of spontaneous phage production than when residing in
      the native LESB58 host. We show that LES phages are capable of horizontal gene
      transfer by infecting P. aeruginosa strains from different sources and that type
      IV pili are required for infection by all three phages. CONCLUSIONS: Multiple
      inducible prophages with diverse infection properties have been maintained in the
      LES genome. Our data suggest that LESphi2 is more sensitive to induction into the
      lytic cycle or has a more efficient replicative cycle than the other LES phages.

PMID- 22998635
TI  - The influence of social structure on brood survival and development in a socially
      polymorphic ant: insights from a cross-fostering experiment.
AB  - Animal societies vary in the number of breeders per group, which affects many
      socially and ecologically relevant traits. In several social insect species,
      including our study species Formica selysi, the presence of either one or
      multiple reproducing females per colony is generally associated with differences
      in a suite of traits such as the body size of individuals. However, the proximate
      mechanisms and ontogenetic processes generating such differences between social
      structures are poorly known. Here, we cross-fostered eggs originating from single
      queen (= monogynous) or multiple-queen (= polygynous) colonies into experimental
      groups of workers from each social structure to investigate whether differences
      in offspring survival, development time and body size are shaped by the genotype
      and/or prefoster maternal effects present in the eggs, or by the social origin of
      the rearing workers. Eggs produced by polygynous queens were more likely to
      survive to adulthood than eggs from monogynous queens, regardless of the social
      origin of the rearing workers. However, brood from monogynous queens grew faster
      than brood from polygynous queens. The social origin of the rearing workers
      influenced the probability of brood survival, with workers from monogynous
      colonies rearing more brood to adulthood than workers from polygynous colonies.
      The social origin of eggs or rearing workers had no significant effect on the
      head size of the resulting workers in our standardized laboratory conditions.
      Overall, the social backgrounds of the parents and of the rearing workers appear
      to shape distinct survival and developmental traits of ant brood.

PMID- 22998634
TI  - Molecular mechanism of preQ1 riboswitch action: a molecular dynamics study.
AB  - Riboswitches often occur in the 5'-untranslated regions of bacterial mRNA where
      they regulate gene expression. The preQ(1) riboswitch controls the biosynthesis
      of a hypermodified nucleoside queuosine in response to binding the queuosine
      metabolic intermediate. Structures of the ligand-bound and ligand-free states of
      the preQ(1) riboswitch from Thermoanaerobacter tengcongensis were determined
      recently by X-ray crystallography. We used multiple, microsecond-long molecular
      dynamics simulations (29 MUs in total) to characterize the structural dynamics of
      preQ(1) riboswitches in both states. We observed different stabilities of the
      stem in the bound and free states, resulting in different accessibilities of the
      ribosome-binding site. These differences are related to different stacking
      interactions between nucleotides of the stem and the associated loop, which
      itself adopts different conformations in the bound and free states. We suggest
      that the loop not only serves to bind preQ(1) but also transmits information
      about ligand binding from the ligand-binding pocket to the stem, which has
      implications for mRNA accessibility to the ribosome. We explain functional
      results obscured by a high salt crystallization medium and help to refine regions
      of disordered electron density, which demonstrates the predictive power of our
      approach. Besides investigating the functional dynamics of the riboswitch, we
      have also utilized this unique small folded RNA system for analysis of
      performance of the RNA force field on the MUs time scale. The latest AMBER
      parmbsc0chi(OL3) RNA force field is capable of providing stable trajectories of
      the folded molecule on the MUs time scale. On the other hand, force fields that
      are not properly balanced lead to significant structural perturbations on the sub
      MUs time scale, which could easily lead to inappropriate interpretation of the
      simulation data.

PMID- 22998636
TI  - Effect of parenteral administration of glutamine on autophagy of liver cell and
      immune responses in weaned calves.
AB  - The objectives of this study were to determine the effects of an increased
      jugular supply of L-Gln on post-weaning growth, immune responses, intestinal
      morphology and autophagy of weaned calves. At 35 days of age, 24 Holstein calves
      (initial 50 +/- 1.5 kg; 35 +/- 2 day of age) were randomly allocated to four
      treatments, and each treatment included five male and one female calves. Holstein
      calves were assigned to treatments of (i) i.v. infusion of 2 l of 0.85% NaCl,
      Control group [C]; (ii) i.v. infusion of 8 g/day of L-Gln mixed with 2 l of 0.85%
      NaCl solution [L]; (iii) i.v. infusion of 16 g/day of L-Gln mixed with 2 l of
      0.85% NaCl solution [M]; and (iv) i.v. infusion of 32 g/day of L-Gln mixed with 2
      l of 0.85% NaCl [H]; The infusion was 2 h/day for each of 14 consecutive days
      starting on day 1 after weaning. Feed and water were freely available to all
      calves. All calves were killed on the 14th day post-weaning for measurements of
      autophagy of liver cell and intestinal morphology. Gln has no effect on dry
      matter intake (DMI) and average daily gain (ADG). Gln infusion increased
      quadratically the abundance of CD4+, monocyte and the ratio of CD4+/CD8+. The
      urea N, Gln and Glucose in plasma increased linearly with increasing Gln loads.
      Gln infusion increased quadratically villus height and crypt depth of intestine.
      The autophagy level of liver cell was improved with the Gln infusion dose
      increased. 

PMID- 22998637
TI  - American Academy of Pain Medicine response to PROP petition to the FDA that seeks
      to limit pain medications for legitimate noncancer pain sufferers.

PMID- 22998638
TI  - Roles of proteins, polysaccharides, and phenolics in haze formation in white wine
      via reconstitution experiments.
AB  - Residual proteins in finished wines can aggregate to form haze. To obtain
      insights into the mechanism of protein haze formation, a reconstitution approach
      was used to study the heat-induced aggregation behavior of purified wine
      proteins. A chitinase, four thaumatin-like protein (TLP) isoforms, phenolics, and
      polysaccharides were isolated from a Chardonnay wine. The same wine was stripped
      of these compounds and used as a base to reconstitute each of the proteins alone
      or in combination with the isolated phenolics and/or polysaccharides. After a
      heating and cooling cycle (70  degrees C for 1 h and 25  degrees C for 15 h), the
      size and concentration of the aggregates formed were measured by scanning ion
      occlusion sensing (SIOS), a technique to detect and quantify nanoparticles. The
      chitinase was the protein most prone to aggregate and the one that formed the
      largest particles; phenolics and polysaccharides did not have a significant
      impact on its aggregation behavior. TLP isoforms varied in susceptibility to haze
      formation and in interactions with polysaccharides and phenolics. The work
      establishes SIOS as a useful method for studying wine haze.

PMID- 22998639
TI  - Rapid loading of intravenous lacosamide: efficacy and practicability during
      presurgical video-EEG monitoring.
AB  - PURPOSE: This study investigates immediate efficacy and safety of intravenous
      application of de novo lacosamide (LCM) as add-on therapy in patients with
      pharmacoresistant focal epilepsy. METHODS: During presurgical video
      electroencephalography (EEG) monitoring, 17 adult inpatients received LCM
      infusion (200 mg every 12 h for 2-3 days) followed by oral formulation with the
      same regimen. Before and after intravenous application of LCM, seizures and
      interictal epileptiform discharges (IEDs) recorded with continuous video-EEG
      monitoring were analyzed, and an assessment of adverse events (AEs) was performed
      daily. To evaluate the midterm tolerability and efficacy, follow-up visits were
      conducted 1 and 3 months after discharge from hospital. KEY FINDINGS: In the
      acute phase, intravenous initiation of LCM was well tolerated with few mild or
      moderate AEs (3 of 17, 17.6%). A significant reduction of seizure frequency in
      the treatment phase as compared to mean seizure frequency in the 2-day baseline
      phase was achieved (p < 0.05 for the first treatment day, and p < 0.005 for the
      second treatment day). On the first treatment day, 61.5% of the patients were
      seizure free, and 84.6% on the second treatment day. IED reduction after
      intravenous application of LCM was not significant. After 1 month, the 50%
      responder rate was 46.6% and after the 3-month period, 42.8%. SIGNIFICANCE: Our
      data suggest that rapid intravenous initiation of de novo LCM is safe and may
      protect against seizures in a rapid and midterm time window.

PMID- 22998641
TI  - Novel treatment avenues for peripheral T-cell lymphomas.
AB  - INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) and natural killer (NK) or T
      cell non-Hodgkin's lymphomas (NHLs) are a rare and heterogeneous class of
      diseases with generally poor prognosis. This work intends to provide a focused
      primer on clinical diagnosis, current treatment regimens, and novel therapeutic
      approaches. The recent WHO classification has defined 18 different subtypes of
      PTCL and NK T-cell lymphomas. Diagnosis is mainly based on histology, flow
      cytometric analysis of surface molecules in the blood and bone marrow,
      cytogenetics/fluorescence in situ hybridization (FISH), and T-cell receptor (TCR)
      rearrangement. Staging as well as follow-up diagnostic procedures rely on imaging
      techniques such as computerized tomography (CT) and positron emission tomography
      (PET). Current chemotherapeutic regimens such as CHOP result in a 60 - 70%
      response rate; however, 5-year survival is only around 30%. Therefore, new
      treatment strategies are urgently needed. Currently, different drug classes are
      under scrutiny. AREAS COVERED: The authors discuss substances that directly
      target the tumor cells. The article includes such substances as antimetabolites,
      antibodies, histone deacetylase inhibitors, tyrosine kinase inhibitors, and
      immunomodulatory substances such as lenalidomide. EXPERT OPINION: In the future a
      close collaboration of geneticists, biochemists, and clinicians together with new
      technologies such as deep sequencing will allow the refinement of treatment
      strategies in many diseases including PTCLs and NHLs. This refinement will allow
      treatments to be prepared according to the need of the individual patient.

PMID- 22998642
TI  - Design and evaluation of matrix diffusion controlled transdermal patches of
      coumarin.
AB  - The aim of the present investigation was to prepare coumarin matrix transdermal
      systems using the combinations of Eudragit RL-100/Eudragit RS-100. The
      formulations were evaluated for various physicochemical properties (thickness,
      weight variation, drug content uniformity, moisture content and water absorption
      uptake), in vitro release studies, in vitro skin permeation studies and skin
      irritation studies. In vitro skin permeation and skin irritation studies were
      carried out on rat skin and rabbit respectively. The drug-polymer interaction
      results revealed no interaction between the drug and the polymers. Drug content
      uniformity of the patches was found more than 98%. Variations in drug permeation
      profiles were observed among the formulations. From the results concluded that
      coumarin can be formulated into the transdermal matrix type patches to overcome
      the first pass effect, reduced frequency of administration of coumarin and
      sustain its release characteristics; the polymeric composition Eudragit RL and
      Eudragit RS (1:1) with 1mL of ethanol was found to be the best choice for the
      formulation of transdermal patches of coumarin among the formulation studied.

PMID- 22998643
TI  - Coexistent bullous and pustular mycosis fungoides in a patient with
      staphylococcal sepsis.

PMID- 22998644
TI  - Effects of salinity and ultraviolet radiation on the bioaccumulation of
      mycosporine-like amino acids in Artemia from Lake Urmia (Iran).
AB  - We investigated the effects of salinity and artificial UV radiation on the
      accumulation of mycosporine-like amino acids (MAAs) in sexual and parthenogenetic
      Artemia from Lake Urmia. The nauplii hatched from the cysts were cultured until
      adulthood under two salinities (150 and 250 g L(-1) ) and two light treatments
      (PAR and PAR+UVR) in the laboratory. Finally, the Artemia were analyzed for their
      concentration of MAAs. In most of the cases, the higher salinity level applied
      was found to increase the MAA concentrations in both Artemia populations
      significantly. The acquisition efficiency of MAAs in both Artemia populations
      increased under exposure to UVR-supplemented photosynthetically active radiation
      (PAR) compared to those raised under PAR, except for Porphyra-334. It was
      observed that combination of UV radiation and elevated salinity significantly
      increased the bioaccumulation of MAAs. Thus, the presence of these compounds in
      these populations of Artemia may increase their adaptability for living in high
      UV and high-salinity conditions prevailing in Lake Urmia. Higher concentrations
      of MAAs in the parthenogenetic population of Artemia could be probably attributed
      to its mono sex nature and higher adaptation capacities to extreme environmental
      conditions.

PMID- 22998645
TI  - Meeting complex needs: young people with HIV in London.
AB  - OBJECTIVES: The aim of the study was to examine the service use and
      characteristics of young people diagnosed with HIV infection aged under 25 years
      in order to design appropriate services. METHODS: A retrospective review of
      medical records of all individuals diagnosed as HIV positive aged under 25 years
      at Chelsea and Westminster Hospital, London, UK was carried out. The Health
      Protection Agency traced all individuals who had been lost to follow-up. We
      collected demographic, clinical, social and behavioural data. RESULTS: Of the 100
      individuals diagnosed as HIV positive aged <25 years, 91% acquired HIV sexually;
      the median age at diagnosis was 21 years. Fifty-nine per cent were born outside
      the UK. Of 91 individuals diagnosed in the UK, 20% were diagnosed outside
      genitourinary medicine. Almost half had tested HIV negative a median of 13 months
      previously. At HIV diagnosis, 26% had a concurrent sexually transmitted
      infection; thereafter 34% had a documented risk of HIV transmission. The
      prevalence of psychiatric comorbidity was high (23%). Cervical screening rates
      were low; of nine women screened, five required treatment for cervical or vulval
      neoplasia. One fifth of the cohort were lost to follow-up a median 6 months from
      diagnosis. CONCLUSIONS: Young people with sexually acquired HIV infection have
      complex medical and psychosocial needs and many disengage from health services.
      Current services are not meeting the needs of these young people. Specialist
      young people's clinics may improve standards of care for this vulnerable group.

PMID- 22998646
TI  - Cost-effectiveness analysis of anti-muscarinic agents for the treatment of
      overactive bladder.
AB  - OBJECTIVE: To determine the cost-effectiveness of pharmacologic treatments for
      overactive bladder (OAB) in the US. METHODS: A decision model was constructed
      based on studies of effectiveness, adverse consequences, co-morbid conditions,
      and medical costs for the treatment of OAB. Treatment success was defined as no
      incontinence episodes for 3-7 days or 3-7 consecutive dry days. Estimates of
      treatment success were obtained from clinical trials and included darifenacin,
      fesoterodine, oxybutynin immediate release (IR), oxybutynin extended release
      (ER), oxybutynin topical gel, oxybutynin transdermal patch, solifenacin,
      tolterodine IR, tolterodine ER, trospium IR, and trospium ER. Probabilistic
      sensitivity analysis was conducted using Monte Carlo simulation. RESULTS: A total
      of 51 OAB studies were identified and 11 reported treatment success. Mean
      continence rates varied in the literature from 21.0% with trospium IR to 51.0%
      with solifenacin. The 95% CI for solifenacin's success rate was statistically
      higher than other regimens due to the higher continence rates from the clinical
      trials. Oxybutynin IR and oxybutynin ER were significantly less costly than other
      products. The product with the lowest incremental cost-effectiveness ratio (ICER)
      relative to oxybutynin IR was solifenacin at $1338 (+/- 168) per additional
      continent patient. The cost-effectiveness acceptability curve indicated that
      oxybutynin IR was the most cost-effective regimen when willingness-to-pay values
      were less than $10,000 per additional continent patient. Solifenacin was most
      cost-effective at higher willingness-to-pay values. CONCLUSION: There was broad
      overlap in effectiveness among the anti-muscarinic products, except solifenacin
      had a significantly higher continence rate. Oxybutynin IR and oxybutynin ER were
      significantly less costly than other anti-muscarinic regimens, and these two
      products have a useful role to play in the management of OAB. However, for
      patients unable to tolerate the lower cost products, formularies benefit from
      solifenacin among branded products since the cost-effectiveness acceptability
      curve demonstrated it was the product most likely to be cost-effective after
      oxybutynin IR.

PMID- 22998647
TI  - The impact of quality of work life on job embeddedness and affective commitment
      and their co-effect on turnover intention of nurses.
AB  - AIMS AND OBJECTIVES: To verify with empirical evidence the hypothesised relation
      and the effect of quality of work life, job embeddedness and affective commitment
      on turnover intention of clinical nurses in China. BACKGROUND: High turnover of
      the nursing workforce in healthcare organisations is a difficult and recurring
      problem in China as well as in many other countries in the world. It leads to
      great waste of resources and increases management cost. Developing and retaining
      the nursing workforce, which is a major challenge faced by human resources
      practitioners in hospitals and public health agencies, also becomes a subject of
      interest for management studies. Most of the literature about voluntary turnover
      focused on such traditional measures as job satisfaction and job alternatives in
      the past. The introduction of such new concepts as quality of work life, job
      embeddedness and affective commitment, which views the issue from a much broader
      and comprehensive spectrum, made a great breakthrough in the turnover study. In
      this study, we selected quality of work life, job embeddedness and affective
      commitment - three of the most important factors in employer-employee relations -
      and analysed the interaction between each one of them, as well as their co-effect
      on turnover intention of Chinese nurses. METHODS: Cross-sectional survey and
      structural equation modelling were applied in studying the self-report
      questionnaires distributed to 1000 nurses employed in five large-scale government
      owned hospitals in Heilongjiang Province, Northeast China. FINDINGS: Our study
      confirmed the hypothesised positive relation of quality of work life with job
      embeddedness and affective commitment and the hypothesised negative relation of
      quality of work life with turnover intention, that is, high quality of work life
      perceived by the nurses enhances their job embeddedness and affective commitment
      and thus reduces their intention to leave the job. CONCLUSIONS: The effect of
      quality of work life is positive on job embeddedness and affection commitment and
      negative on turnover intention. RELEVANCE TO CLINICAL PRACTICE: Nurse managers
      should pay great attention to the nurses' perception of quality of work life, and
      make great efforts in developing strategies and projects that can strengthen the
      nurses' embeddedness or connection with the job.

PMID- 22998648
TI  - Identification of an aggregation-prone structure of tau.
AB  - The aggregation and deposition of normally soluble proteins is the hallmark of
      several devastating neurodegenerative disorders. For proteins such as tau in
      Alzheimer's disease and alpha-synuclein in Parkinson's disease, aggregation
      involves a transition from an intrinsically disordered monomer to a highly
      structured fiber. While understanding the role of these proteins in
      neurodegeneration requires elucidation of the structural basis of self
      association, the conformational heterogeneity of disordered proteins makes their
      structural characterization inherently challenging. Here we use single molecule
      Forster resonance energy transfer to measure the conformational ensemble of tau
      in the absence and presence of heparin to identify critical conformational
      changes relevant to the initiation of aggregation. We find that different domains
      of tau display distinct conformational properties that are strongly correlated
      with their degree of disorder and that may relate to their roles in aggregation.
      Moreover, we observe that heparin binding induces a distinct two-state structural
      transition in tau characterized by a loss of long-range contacts and a
      concomitant compaction of the microtubule binding domain. Our results describe a
      conformational intermediate of tau that precedes the formation of aggregates and
      could serve as a target for tau-focused therapeutics.

PMID- 22998649
TI  - Polysorbate 80 and Helicobacter pylori: a microbiological and ultrastructural
      study.
AB  - BACKGROUND: The frequent occurrence of chemoresistant strains reduces the chances
      of eradication of H. pylori infection and prompted the investigation of non
      antibiotic substances active against this organism. Some surfactants enhance the
      effectiveness of antibiotics for their permeabilizing properties towards
      bacteria. We examined the antimicrobial activity to H. pylori of the surfactant
      polysorbate 80, used alone and in association with amoxicillin, clarithromycin,
      metronidazole, levofloxacin and tetracycline. We also aimed to study the
      ultrastructural alterations caused upon H. pylori by polysorbate 80, alone and in
      combination with antibiotics. Twenty-two H. pylori strains were tested using the
      broth dilution method. After incubation, broth from each dilution was subcultured
      onto agar enriched with foetal bovine serum to determine the minimum bactericidal
      concentration (MBC). Synergistic effect of polysorbate 80 with antibiotics was
      investigated by the broth dilution and disc diffusion techniques. Ultrastructural
      alterations of organisms treated with polysorbate 80, alone and in association
      with antibiotics were analyzed by transmission electron microscopy. RESULTS: MBCs
      of polysorbate 80 ranged from 2.6 (1.1) MUg/ml to 32 (0) MUg/ml. Polysorbate 80
      exerted a synergistic effect when associated with metronidazole and
      clarithromycin: polysorbate 80 and metronidazole MBCs decreased by >= 4 fold;
      clarithromycin MBCs for two resistant strains decreased by 20 and 1000 times. The
      principal alteration caused by polysorbate 80 consisted in the detachment of the
      outer membrane of bacteria. CONCLUSIONS: The bactericidal activity of polysorbate
      80 and the synergistic effect of the association with metronidazole and
      clarithromycin could be useful in the treatment of H. pylori infection.

PMID- 22998650
TI  - Coexistence of macro- and micro-vascular abnormalities in newly diagnosed normal
      tension glaucoma patients.
AB  - PURPOSE: To investigate the coexistence of ocular microvascular and systemic
      macrovascular abnormalities in early stage, newly diagnosed and previously
      untreated normal tension glaucoma patients (NTG). METHODS: Retinal vascular
      reactivity to flickering light was assessed in 19 NTG and 28 age-matched controls
      by means of dynamic retinal vessel analysis (IMEDOS GmbH, Jena, Germany). Using a
      newly developed computational model, the entire dynamic vascular response profile
      to flicker light was imaged and used for analysis. In addition, assessments of
      carotid intima-media thickness (IMT) and pulse wave analysis (PWA) were conducted
      on all participants, along with blood pressure (BP) measurements and blood
      analyses for lipid metabolism markers. RESULTS:  Patients with NTG demonstrated
      an increased right and left carotid IMT (p = 0.015, p = 0.045) and an elevated
      PWA augmentation index (p = 0.017) in comparison with healthy controls, along
      with an enhanced retinal arterial constriction response (p = 0.028), a steeper
      retinal arterial constriction slope (p = 0.031) and a reduced retinal venous
      dilation response (p = 0.026) following flicker light stimulation. CONCLUSIONS:
      Early stage, newly diagnosed, NTG patients showed signs of subclinical vascular
      abnormalities at both macro- and micro-vascular levels, highlighting the need to
      consider multi-level circulation-related pathologies in the development and
      progression of this type of glaucoma.

PMID- 22998651
TI  - Functional analyses of individual mating-type transcripts at MAT loci in Fusarium
      graminearum and Fusarium asiaticum.
AB  - Members of the Fusarium graminearum species (Fg) complex, which are homothallic
      ascomycetous species, carry two opposite mating-type (MAT) loci in a single
      nucleus for controlling sexual development. We investigated the roles of three
      (MAT1-1-1, MAT1-1-2, and MAT1-1-3) and two (MAT1-2-1 and MAT1-2-3) transcripts
      located at both loci in representative Fg complex species (F. graminearum and
      Fusarium asiaticum). In self-fertile F. graminearum strains, the transcript
      levels of MAT1-1-1, MAT1-2-1, and MAT1-2-3 peaked 2 days after sexual induction
      (dai) and then remained high until 12 dai, whereas MAT1-1-2 and MAT1-1-3
      transcripts reached peak levels between 4 and 8 dai. In contrast, all of the MAT
      transcripts in self-sterile F. asiaticum strains accumulated at much lower levels
      than those in F. graminearum during the entire time. Targeted gene deletions
      confirmed that MAT1-1-1, MAT1-1-2, MAT1-1-3, and MAT1-2-1 were essential for self
      fertility in F. graminearum, but MAT1-2-3 was not. All MAT-deleted strains
      (except DeltaMAT1-2-3) produced recombinant perithecia when outcrossed to a self
      fertile strain. These results indicate that developmental up-regulation of the
      individual MAT genes in both a proper fashion and quantity is critical for sexual
      development, and that alterations in the gene expression could be attributed to
      the variation in self-sterility among the Fg complex.

PMID- 22998652
TI  - Unusual optical resolution of all four tryptophan residues in MPT63 protein by
      phosphorescence spectroscopy: assignment and significance.
AB  - MPT63, a secreted protein of unknown function that is specific to Mycobacterium
      tuberculosis and a potential drug target, contains four Tryptophan (Trp/W)
      residues located at positions 26, 48, 82, and 129 in the amino acid sequence. All
      of the four Trp residues have been optically resolved by simple inexpensive
      phosphorescence spectroscopy at 77 K. The protein architecture provides a
      delicate micro-environment and location of Trp residues giving rise to four
      different (0,0) bands in the phosphorescence spectra. Calculation of intra Trp
      energy transfer (ET) efficiency, accessible surface area (ASA) of Trp residues,
      and environment of Trp in the wild-type (WT) and the mutant W26F [where, Trp 26
      is replaced by phenyl alanine (Phe/F)] reveal: E(T1) (W82) > E(T1) (W48) > E(T1)
      (W129) > E(T1) (W26), where E(T1) is the lowest (pi-pi*) triplet state energy of
      Trp. The (0,0) band observed at 421.6 nm assigned for Trp 26 is found to be the
      longest wavelength (0,0) band so far reported in the literature. Fluorescence in
      WT and W26F is dominated by buried or partially exposed Trp residues indicated by
      time-resolved spectra. Circular Dichroism (CD) studies and the time-resolved
      anisotropy measurement confirm the unaltered secondary and tertiary structure of
      the mutant compared to that of the WT. Excitation energy dependent
      phosphorescence spectra suggest that the intensity of the different (0,0) bands
      could be tuned and Tyrosine (Tyr/Y) residue is silent in emission. Optical
      resolution of all the Trp residues will help understand the role of each Trp
      residue in the folding/unfolding mechanism and in the interaction with other
      systems.

PMID- 22998653
TI  - Indium-promoted Reformatsky reaction: a straightforward access to beta-amino and
      beta-hydroxy alpha,alpha-difluoro carbonyl compounds.
AB  - A versatile and practical methodology to access beta-amino and beta-hydroxy
      alpha,alpha-difluoro carbonyl compounds using indium metal is described. This
      methodology has been successfully applied to a broad range of substrates
      including aldehydes, ketones, and imines, affording the corresponding and highly
      valuable gem-difluoro esters. The wide substrate scope highlights the
      chemoselectivity of the process.

PMID- 22998654
TI  - Communicating with parents about vaccination: a framework for health
      professionals.
AB  - BACKGROUND: A critical factor shaping parental attitudes to vaccination is the
      parent's interactions with health professionals. An effective interaction can
      address the concerns of vaccine supportive parents and motivate a hesitant parent
      towards vaccine acceptance. Poor communication can contribute to rejection of
      vaccinations or dissatisfaction with care. We sought to provide a framework for
      health professionals when communicating with parents about vaccination. METHODS:
      Literature review to identify a spectrum of parent attitudes or 'positions' on
      childhood vaccination with estimates of the proportion of each group based on
      population studies. Development of a framework related to each parental position
      with determination of key indicators, goals and strategies based on communication
      science, motivational interviewing and valid consent principles. RESULTS: Five
      distinct parental groups were identified: the 'unquestioning acceptor' (30-40%),
      the 'cautious acceptor' (25-35%); the 'hesitant' (20-30%); the 'late or selective
      vaccinator' (2-27%); and the 'refuser' of all vaccines (<2%). The goals of the
      encounter with each group will vary, depending on the parents' readiness to
      vaccinate. In all encounters, health professionals should build rapport, accept
      questions and concerns, and facilitate valid consent. For the hesitant, late or
      selective vaccinators, or refusers, strategies should include use of a guiding
      style and eliciting the parent's own motivations to vaccinate while, avoiding
      excessive persuasion and adversarial debates. It may be necessary to book another
      appointment or offer attendance at a specialised adverse events clinic. Good
      information resources should also be used. CONCLUSIONS: Health professionals have
      a central role in maintaining public trust in vaccination, including addressing
      parents' concerns. These recommendations are tailored to specific parental
      positions on vaccination and provide a structured approach to assist
      professionals. They advocate respectful interactions that aim to guide parents
      towards quality decisions.

PMID- 22998655
TI  - Mono- and combination drug therapies in hospitalized patients with bipolar
      depression. Data from the European drug surveillance program AMSP.
AB  - BACKGROUND: For the pharmacological treatment of bipolar depression several
      guidelines exist. It is largely unknown, to what extent the prescriptions in
      daily clinical routine correspond to these evidence based recommendations and
      which combinations of psychotropic drugs are frequently used. METHODS: The
      prescriptions of psychotropic drugs were investigated of all in-patients with
      bipolar depression (n = 2246; time period 1994-2009) from hospitals participating
      in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were
      analysed additionally. RESULTS: From 1994 to 2009, 85% of all patients received
      more than one class of psychotropic substances: 74% received antidepressants in
      combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium.
      When given in combination, lithium is the most often prescribed substance for
      bipolar depression (33%), followed by valproic acid (23%), mirtazapine and
      venlafaxine (16% each), quetiapine (15%), lamotrigine (14%) and olanzapine (13%).
      Both, lithium and valproic acid are often combined with selective serotonin
      reuptake inhibitors (SSRI), but also with mirtazapine und venlafaxine.
      Combinations of more than one antidepressant occur quite often, whereby
      combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare.
      In 2010, quetiapine (alone and combined) was the most frequently prescribed drug
      (39%); aripiprazole was administered in 10%. CONCLUSION: Combinations of
      antidepressants (SSRI, mirtazapine, venlafaxine) with mood stabilizers (lithium,
      valproic acid, lamotrigine) and / or atypical antipsychotics (quetiapine,
      olanzapine) are common. Of most of those combinations the efficacy has not been
      studied. The use of aripiprazole and the concomitant use of two or three
      antidepressants contrast the guidelines.

PMID- 22998656
TI  - Comparison of the effectiveness of two protocols for treating nursing home
      residents with advanced dementia.
AB  - The Serial Trial Intervention (STI) is a decision support tool to address the
      problem of underassessment and undertreatment of pain and other unmet needs of
      people with dementia. This study compared the effectiveness of the 5-step and 9
      step versions of the STI using a two-group repeated measures quasi-experimental
      design with randomization of 12 matched nursing homes. The sample consisted of
      125 residents with moderate to severe dementia. Both the 5- and 9-step STIs
      significantly decreased discomfort and agitation from pre- to posttest (effect
      sizes = 0.45 to 0.90). The 9-step version was more effective for comorbid burden
      and increased cortisol slope (effect sizes = 0.50 and 0.49). Process variables
      were all statistically significantly improved using the 9-step STI. Nurse time
      was not different between the two groups. The clinical decision support rules
      embedded in the STI, particularly the 9-step version, helped nurses change
      practice and improved resident outcomes.

PMID- 22998657
TI  - Nursing home culture change: what does it mean to nurses?
AB  - The purpose of this study was to explore, from the perspectives of licensed
      nurses, the organizational culture, work environment, and factors influencing
      culture change in two nursing homes participating in the Wellspring Program. All
      licensed nurses >= 0.25 full-time equivalent from two nursing homes were invited
      to complete the Organizational Culture Inventory and the Work Environment Scale.
      A subset of respondents was invited to participate in subsequent interviews. Data
      indicated unresolved conflict, low employee satisfaction, high work demands, and
      managerial control in the workplace. Qualitatively, three categories emerged:
      Confusion over culture change, role, and documentation; Conflict over the
      integration of traditional care with a resident-centered model; and Commitment to
      providing quality nursing care to the resident. To ensure the successful
      implementation of culture change, consideration must be given to clarity of
      communication, anticipation of role conflict, and building on the underlying
      strength of job commitment.

PMID- 22998658
TI  - Caregiver-resident interaction with Barnard's Feeding Scale.
AB  - This exploratory study was done first to determine the appropriateness of
      Barnard's Feeding Scale (BFS) as a measure of dyadic interaction between
      caregivers and residents with dementia. Seventy-five of the 76 discrete BFS
      behaviors were observed during the feedings, thus indicating appropriateness of
      the BFS. Then, 228 dyadic feedings were observed and scored to achieve the second
      purpose: to numerically describe caregiver-resident interaction during mealtimes
      in two nursing homes. Results showed caregivers in both nursing homes
      demonstrated the highest interaction scores on BFS subscale Response to Distress
      and the lowest scores on two of the caregiver subscales, Sensitivity to Cues and
      Social-Emotional Responsiveness. Caregivers' total mean scores correlated (r =
      0.523) with those of residents. The third purpose of the study was accomplished
      using quantitative data to begin exploring the potential influence of participant
      and other factors during feeding. Clinically, the specific behavioral items of
      the BFS provide objective assessment of caregiver-resident interaction during
      feeding.

PMID- 22998659
TI  - Sundown syndrome: a systematic review of the literature.
AB  - The label sundown syndrome continues to be frequently used in long-term and acute
      care settings without consistent meaning. This study adds to the understanding of
      this label by synthesizing findings from research published since 1987 linked to
      sundown syndrome. The purpose of this systematic review is to describe,
      synthesize, and critique the theoretical definitions, operational definitions and
      measurement methods, prevalence, antecedent and precipitating factors and
      consequences, and effectiveness of interventions for sundown syndrome found in
      the published literature. Implications for research and practice are presented.

PMID- 22998661
TI  - Complementary/alternative therapy use in older women with arthritis.
AB  - The purpose of this study was to describe the experiences of using
      complementary/alternative therapy (C/AT) in community-dwelling older women with
      arthritis. A descriptive qualitative approach using focus groups for data
      collection was conducted with a purposive sample of 27 older female C/AT users
      (mean age = 77.8, range = 65 to 93). Content analysis was used to identify
      themes, which included (a) acceptance of the incurable nature of arthritis, (b)
      high use of nutritional supplements, (c) use of multiple C/AT to manage symptoms,
      (d) physical symptoms and limited treatment options motivated C/AT use, (e) most
      C/AT were perceived as effective, (f) C/AT knowledge was limited among users, and
      (g) older women did not fully disclose their C/AT use to their primary care
      physician. Findings revealed that older women are motivated to use C/AT,
      particularly nutritional supplements, to manage arthritis symptoms without
      seeking medical advice from their physician. Strategies are needed to improve
      communication between health care providers and older patients on C/AT use for
      optimal management of arthritis and prevention of adverse events.

PMID- 22998660
TI  - Influences on neighborhood walking in older adults.
AB  - The purpose of this cross-sectional survey study was to examine the influence of
      self-efficacy, outcome expectations, and environment on neighborhood walking in
      older adults with (n = 163, mean age = 78.7, SD = 7.96 years) and without (n =
      163, mean age = 73.6, SD = 7.93 years) mobility limitations, controlling for
      demographic characteristics. Multiple regression revealed that in mobility
      limited older adults, demographic characteristics, self-efficacy, and outcome
      expectations explained 17.4% of variance in neighborhood walking, while
      environment (neighborhood destinations and design) explained 9.4%. Destinations,
      self-efficacy, sex, and outcome expectations influenced walking. In those without
      mobility limitations, demographic characteristics, self-efficacy, and outcome
      expectations explained 15.6% of the variance, while environment explained 5.6%.
      Self-efficacy, sex, and design influenced walking. Neighborhood walking
      interventions for older adults should include self-efficacy strategies tailored
      to mobility status and neighborhood characteristics.

PMID- 22998662
TI  - Can a licorice lollipop decrease cariogenic bacteria in nursing home residents?
AB  - The purpose of this pilot study was to examine whether an herbal lollipop
      containing licorice root decreases Streptococcus mutans (S. mutans) bacteria that
      cause dental caries in nursing home residents. A total of 8 residents (5 women, 3
      men; mean age = 85) consented to participate in this study. Participants were
      offered two lollipops per day for 21 days. Saliva samples were collected at
      baseline and Days 1, 3, 7, 14, and 21, then analyzed for numbers of S. mutans.
      Using linear mixed-models analysis with difference in numbers of S. mutans from
      baseline to any time point as the dependent variable, and number of lollipops
      consumed with effect of time controlled as the predictor variable, participants
      who consumed more lollipops during the 21-day time period were more likely to
      have fewer numbers of S. mutans (beta = -8.703, p = 0.067). There was a trend
      toward reduction of S. mutans with consumption of more lollipops during the 21
      day period. Recruiting a larger sample for future research may demonstrate a
      significant reduction.

PMID- 22998663
TI  - Efficacy of a numerical value of a fixed-effect estimator in stochastic frontier
      analysis as an indicator of hospital production structure.
AB  - BACKGROUND: The casemix-based payment system has been adopted in many countries,
      although it often needs complementary adjustment taking account of each
      hospital's unique production structure such as teaching and research duties, and
      non-profit motives. It has been challenging to numerically evaluate the impact of
      such structural heterogeneity on production, separately of production
      inefficiency. The current study adopted stochastic frontier analysis and proposed
      a method to assess unique components of hospital production structures using a
      fixed-effect variable. METHODS: There were two stages of analyses in this study.
      In the first stage, we estimated the efficiency score from the hospital
      production function using a true fixed-effect model (TFEM) in stochastic frontier
      analysis. The use of a TFEM allowed us to differentiate the unobserved
      heterogeneity of individual hospitals as hospital-specific fixed effects. In the
      second stage, we regressed the obtained fixed-effect variable for structural
      components of hospitals to test whether the variable was explicitly related to
      the characteristics and local disadvantages of the hospitals. RESULTS: In the
      first analysis, the estimated efficiency score was approximately 0.6. The mean
      value of the fixed-effect estimator was 0.784, the standard deviation was 0.137,
      the range was between 0.437 and 1.212. The second-stage regression confirmed that
      the value of the fixed effect was significantly correlated with advanced
      technology and local conditions of the sample hospitals. CONCLUSION: The obtained
      fixed-effect estimator may reflect hospitals' unique structures of production,
      considering production inefficiency. The values of fixed-effect estimators can be
      used as evaluation tools to improve fairness in the reimbursement system for
      various functions of hospitals based on casemix classification.

PMID- 22998664
TI  - Immunoglobulin G (IgG) attenuates neuroinflammation and improves neurobehavioral
      recovery after cervical spinal cord injury.
AB  - BACKGROUND: Evidence suggests that the inflammatory events in the acute phase of
      spinal cord injury (SCI) exacerbate the initial trauma to the cord leading to
      poor functional recovery. As a result, minimizing the detrimental aspects of the
      inflammatory response after SCI is a promising treatment strategy. In this
      regard, immunoglobulin G (IgG) from pooled human serum is a promising treatment
      candidate. Due to its putative, though poorly characterized immuno-modulatory
      effects, IgG has been used clinically to treat neuroinflammatory disorders such
      as Guillain-Barre syndrome, but its effects in neurotrauma remain largely
      unexplored. METHODS: This study examines the potential neuroprotective effects of
      IgG in a well-characterized cervical model of SCI. Female Wistar rats were
      subject to moderate-severe clip compression injury at the C7-T1 level. IgG (0.4
      g/kg) or saline was injected intravenously to randomly selected animals at 15 min
      post SCI. At several time points post SCI, biochemical assays, histology and
      immunohistochemistry analyses, and neurobehavioral assessments were used to
      examine the neuroprotective effects of IgG at the molecular, cellular, and
      neurobehavioral levels. RESULTS: We found that intravenous treatment of IgG
      following acute clip-compression SCI at C7-T1 significantly reduced two important
      inflammatory cytokines: interleukin (IL)-1beta and IL-6. This early reduction in
      pro-inflammatory signaling was associated with significant reductions in
      neutrophils in the spinal cord and reductions in the expression of
      myeloperoxidase and matrix metalloproteinase-9 in the injured spinal cord at 24 h
      after SCI. These beneficial effects of IgG were associated with enhanced tissue
      preservation, improved neurobehavioral recovery as measured by the BBB and
      inclined plane tests, and enhanced electrophysiological evidence of central
      axonal conduction as determined by motor-evoked potentials. CONCLUSION: The
      findings from this study indicate that IgG is a novel immuno-modulatory therapy
      which shows promise as a potential treatment for SCI.

PMID- 22998666
TI  - EuroScore 2 for identification of patients for transapical aortic valve
      replacement--a single center retrospective in 206 patients.
AB  - BACKGROUND: Operative risk scoring algorithms identify patients with severe AS
      for transcatheter valve implantation in whom the anticipated operative mortality
      for conventional surgery would be considered prohibitive. We compared the three
      risk scores EuroScore 1 (LES), society of thoracic surgeons' (STS) score and ACEF
      (age-creatinine-ejection fraction score) to the readjusted EuroScore 2 recently
      presented. METHODS: We reviewed all consecutive patients receiving either
      isolated conventional aortic valve replacement (cAVR) or transapical aortic valve
      implantation (TA-TAVI) in a two-year period (n = 206). 30-days mortality was
      considered as primary endpoint. RESULTS: TA-TAVI was performed in 76 patients,
      isolated cAVR in 130 patients. Overall mortality was 4.4% (TA-TAVI: 7.9%; cAVR:
      2.3%). EuroScore 2 showed a good estimation for the entire population as well as
      within the subgroups: 4,02 +/- 5,36% (TA-TAVI: 6.16 +/- 7.14%, cAVR: 2.77 +/-
      3.42%). Predicted mortalities as assessed by LES were largely overestimated (TA
      TAVI: 27.4 +/- 20.9% cAVR: 10.6 +/- 10.6%, sensitivity: 0.89, specificity: 0.71).
      STS predicted mortality was 6.3 +/- 4.4% for TA-TAVI patients as to 3.2 +/- 3.1%
      for cAVR patients (sens.: 0.22, spec.: 0.96) and ACEF predicted a mortality of
      1.16 +/- 0.36% for cAVR and 1.58 +/- 0.59% for TA-TAVI patients (sens.: 0.78,
      spec.: 0.89). CONCLUSION: The newly refined EuroScore 2 showed a good correlation
      within the studied population. For the individual patient, new cut-offs will have
      to be defined to triage patients for TAVI procedure. A drawback for complex score
      systems such as EuroScore and STS is the lack of recalibration to smaller
      populations as encountered in even large single centers.

PMID- 22998665
TI  - Alternative pathways of human islet amyloid polypeptide aggregation distinguished
      by (19)f nuclear magnetic resonance-detected kinetics of monomer consumption.
AB  - Amyloid formation, a complex process involving many intermediate states, is
      proposed to be the driving force for amyloid-related toxicity in common
      degenerative diseases. Unfortunately, the details of this process have been
      obscured by the limitations in the methods that can follow this reaction in real
      time. We show that alternative pathways of aggregation can be distinguished by
      using (19)F nuclear magnetic resonance (NMR) to monitor monomer consumption along
      with complementary measurements of fibrillogenesis. The utility of this technique
      is demonstrated by tracking amyloid formation in the diabetes-related islet
      amyloid polypeptide (IAPP). Using this technique, we show IAPP fibrillizes
      without an appreciable buildup of nonfibrillar intermediates, in contrast to the
      well-studied Abeta and alpha-synuclein proteins. To further develop the usage of
      (19)F NMR, we have tracked the influence of the polyphenolic amyloid inhibitor
      epigallocatechin gallate (EGCG) on the aggregation pathway. Polyphenols have been
      shown to strongly inhibit amyloid formation in many systems. However,
      spectroscopic measurements of amyloid inhibition by these compounds can be
      severely compromised by background signals and competitive binding with extrinsic
      probes. Using (19)F NMR, we show that thioflavin T strongly competes with EGCG
      for binding sites on IAPP fibers. By comparing the rates of monomer consumption
      and fiber formation, we are able to show that EGCG stabilizes nonfibrillar large
      aggregates during fibrillogenesis.

PMID- 22998667
TI  - Strong specificity in the interaction between parasitoids and symbiont-protected
      hosts.
AB  - Coevolution between hosts and parasites may promote the maintenance of genetic
      variation in both antagonists by negative frequency-dependence if the host
      parasite interaction is genotype-specific. Here we tested for specificity in the
      interaction between parasitoids (Lysiphlebus fabarum) and aphid hosts (Aphis
      fabae) that are protected by a heritable defensive endosymbiont, the gamma
      proteobacterium Hamiltonella defensa. Previous studies reported a lack of
      genotype specificity between unprotected aphids and parasitoids, but suggested
      that symbiont-conferred resistance might exhibit a higher degree of specificity.
      Indeed, in addition to ample variation in host resistance as well as parasitoid
      infectivity, we found a strong aphid clone-by-parasitoid line interaction on the
      rates of successful parasitism. This genotype specificity appears to be mediated
      by H. defensa, highlighting the important role that endosymbionts can play in
      host-parasite coevolution.

PMID- 22998668
TI  - Unusual manifestation of cutaneous cytomegalovirus infection: a nodular cutaneous
      lesion on the finger in a healthy adolescent girl.

PMID- 22998669
TI  - Gut and intestinal passage time in the Rainbow Skink (Trachylepis margaritifer):
      implications for stress measures using faecal analysis.
AB  - Stress levels in organisms provide a rapid measure for assessing population
      health. Handling and capture stress, however, cause error in blood measures, so
      this method is rapidly being replaced by assessing levels of stress metabolites
      in faeces. This eliminates the source of error because there is a lag period
      between stress perception and the resultant stress metabolite accumulation within
      faeces. This lag period is correlated with specific intestinal passage time, a
      measure that can vary greatly between taxa, particularly amongst ectotherms. Due
      to two deleterious consequences associated with extended exposure of the
      metabolites to the intestinal environment, species that exhibit long and variable
      intestinal passage times are not good candidates for metabolite studies. We
      measured gut and intestinal passage times in Trachylepis margaritifer to
      ascertain whether it would be an appropriate candidate for stress metabolite
      studies. We first tested if barium sulphate in the meal had an effect on gut
      passage time at three ambient temperatures (25, 27 and 32  degrees C). Barium
      sulphate had no effect; however, temperature had a significant effect with an
      unexpected pattern: gut passage time was fastest at 32  degrees C but was slower
      at 27  degrees C than at 25  degrees C. We then used X-ray technology and barium
      sulphate-loaded meals to measure gut and intestinal passage times at 25 and 27 
      degrees C. This allowed us to observe which parts of the digestive process were
      responsible for increased passage times at 27  degrees C: the faster passage time
      at 25  degrees C was due to faster intestinal passage time; there was no
      difference in gastric emptying time. We assess the species to be a suitable
      candidate for studies using faeces to measure stress. It is imperative however,
      that the effect of temperature on passage rates is known and taken into account
      in such studies. 

PMID- 22998670
TI  - Carrot beta-carotene degradation and isomerization kinetics during thermal
      processing in the presence of oil.
AB  - The effect of thermal processing (85-130  degrees C) on the stability and
      isomerization of beta-carotene in both an olive oil/carrot emulsion and an olive
      oil phase enriched with carrot beta-carotene was studied. During processing,
      degradation of total beta-carotene took place. Initially, total beta-carotene
      concentration decreased quickly, after which a plateau value was reached, which
      was dependent on the applied temperature. In the oil/carrot emulsion, the total
      beta-carotene concentration could be modeled by a fractional conversion model.
      The temperature dependence of the degradation rate constants was described by the
      activation energy and was estimated to be 45.0 kJ/mol. In the enriched oil phase,
      less degradation took place and the results could not be modeled. Besides
      degradation, beta-carotene isomerization was studied. In both matrices, a
      fractional conversion model could be used to model total isomerization and
      formation of 13-Z- and 15-Z-beta-carotene. beta-Carotene isomerization was
      similar in both the oil/carrot emulsion and enriched oil phase as the
      simultaneously estimated kinetic parameters (isomerization reaction rate constant
      and activation energy) of both matrices did not differ significantly. The
      activation energies of isomerization were estimated to be 70.5 and 75.0 kJ/mol in
      the oil/carrot emulsion and enriched oil phase, respectively.

PMID- 22998671
TI  - Screening for small molecule inhibitors of Toxoplasma gondii.
AB  - INTRODUCTION: Toxoplasma gondii, the agent that causes toxoplasmosis, is an
      opportunistic parasite that infects many mammalian species. It is an obligate
      intracellular parasite that causes severe congenital neurological and ocular
      disease mostly in immunocompromised humans. The current regimen of therapy
      includes only a few medications that often lead to hypersensitivity and toxicity.
      In addition, there are no vaccines available to prevent the transmission of this
      agent. Therefore, safer and more effective medicines to treat toxoplasmosis are
      urgently needed. AREAS COVERED: The author presents in silico and in vitro
      strategies that are currently used to screen for novel targets and unique
      chemotypes against T. gondii. Furthermore, this review highlights the screening
      technologies and characterization of some novel targets and new chemical entities
      that could be developed into highly efficacious treatments for toxoplasmosis.
      EXPERT OPINION: A number of diverse methods are being used to design inhibitors
      against T. gondii. These include ligand-based methods, in which drugs that have
      been shown to be efficacious against other Apicomplexa parasites can be
      repurposed to identify lead molecules against T. gondii. In addition, structure
      based methods use currently available repertoire of structural information in
      various databases to rationally design small-molecule inhibitors of T. gondii.
      Whereas the screening methods have their advantages and limitations, a
      combination of methods is ideally suited to design small-molecule inhibitors of
      complex parasites such as T. gondii.

PMID- 22998672
TI  - Concurrent validity of the non-exercise based VO2max prediction equation using
      percentage body fat as a variable in asian Indian adults.
AB  - BACKGROUND: Aerobic capacity (VO2max) is highly dependent upon body composition
      of an individual and body composition varies with ethnicity. The purpose of this
      study was to check the concurrent validity of the non-exercise prediction
      equation developed by Jackson and colleagues (1990) using percentage body fat as
      a variable in Asian Indian adults. METHODS: One hundred twenty college-aged
      participants (60 male, 60 female, mean age 22.02 +/- 2.29 yrs) successfully
      completed a maximal graded exercise test (GXT) on a motorized treadmill to assess
      VO2max. VO2max was then estimated by the non-exercise prediction equation
      developed by Jackson and colleagues (1990) using percentage body fat. Percentage
      body fat was calculated by three different models (Sandhu et al's fat mass
      equation, Durnin-womersley's 4 site percentage body fat and Jackson & Pollock's 4
      site percentage body fat) and was used in the above equation. The results of
      VO2max obtained using "gold standard" treadmill methods were then compared with
      the three results of VO2max obtained by Jackson et al's equation (using three
      different models to calculate percentage body fat) and it was determined which
      equation is best suited to determine percentage body fat and in turn VO2 max for
      Indian population. RESULTS: Jackson et al's prediction equation overpredicts
      VO2max in Asian Indian subjects who have a lower VO2max (33.41 +/- 14.39
      ml/kg/min) than those reported in other age matched populations. percentage body
      fats calculated by the three equations were significantly different and the
      correlation coefficient (r) between VO2max calculated by Jackson and colleagues
      (1990) using Sandhu et al's equation for percentage body fat with VO2 max
      calculated using treadmill (gold standard) (r = .817) was found slightly more
      significantly correlated than the other two equations and was not statistically
      different from the measured value. CONCLUSIONS: This study proves that VO2max
      equation using Sandhu et al's model for percentage body fat yields more accurate
      results than other studied equations in healthy college-aged participants in
      India.

PMID- 22998673
TI  - Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.
AB  - Rett syndrome is an X-linked neurodevelopmental disorder that manifests in early
      childhood with developmental stagnation, and loss of spoken language and hand
      use, with the development of distinctive hand stereotypies, severe cognitive
      impairment, and autistic features. About 60% of patients have epilepsy. Seizure
      onset before the age of 3 years is unlikely, and onset after age 20 is rare.
      Diagnosis of Rett syndrome is based on key clinical elements that identify
      "typical" Rett syndrome but also "variant" or "atypical" forms. Diagnostic
      criteria have been modified only slightly over time, even after discovering that
      MECP2 gene alterations are present in >90% of patients with typical Rett syndrome
      but only in 50-70% of atypical cases. Over the last several years, intragenic or
      genomic alterations of the CDKL5 and FOXG1 genes have been associated with severe
      cognitive impairment, early onset epilepsy and, often, dyskinetic movement
      disorders, which have variably been defined as Rett variants. It is now clearly
      emerging that epilepsy has distinctive characteristics in typical Rett syndrome
      and in the different syndromes caused by CDKL5 and FOXG1 gene alterations. The
      progressive parting of CDKL5- and FOXG1-gene-related encephalopathies from the
      core Rett syndrome is reflected by the effort to produce clearer diagnostic
      criteria for typical and atypical Rett syndrome. Efforts to characterize the
      molecular pathology underlying these developmental encephalopathies are pointing
      to abnormalities of telencephalic development, neuronal morphogenesis, maturation
      and maintenance, and dendritic arborization.

PMID- 22998674
TI  - Growth and survival parameter estimates and relation  to RpoS levels in serotype
      O157:H7 and non-O157 Shiga  toxin-producing Escherichia coli.
AB  - AIMS: This study analysed the growth and survival of 18 strains of the six
      serotypes of non-O157 Shiga toxin-producing Escherichia coli (STEC) (O26, O45,
      O103, O111, O121 and O145) most frequently implicated in human illness and
      compared them with Escherichia coli O157:H7 strain ATCC43895. METHODS AND
      RESULTS: The data from growth in Luria-Bertani broth (LB)-HCl (pH 4.0, 4.5, 4.8),
      LB-lactate (pH 4.5 and 4.8) and LB-NaCl (5%, 7%) were fitted to modified Gompertz
      equations to enable quantitative comparisons across strains and media conditions.
      Serogroup O45 strains had growth rates that were equal to or significantly
      greater than the O157:H7 control strain in all growth conditions tested. The
      growth rate was independent from the maximum growth achieved, but three strains
      (103A, 121A and 45B) had significantly faster growth and greater maximum cell
      densities in LB-NaCl 5% (strain 103A), LB-HCl pH 4.0 (strain 121A) and LB-NaCl 7%
      (strain 45B). Survival in LB-HCl pH 3.0 of four strains (103C, 111B, 26B and 26C)
      was significantly greater and five strains (26A, 45A, 111A, 121A and 145A) were
      significantly reduced in comparison with the O157:H7 control strain. None of the
      STEC strains had greater survival in LB-NaCl 12% than the O157:H7 control strain.
      A significant association was found between the exponential phase, but not
      stationary phase, RpoS level and survival of STEC. CONCLUSIONS: Some STEC strains
      had growth or survival properties that exceeded those of the O157:H7 control
      strain, but none of the non-O157 STEC had both significantly greater growth and
      survival properties. STEC survival was associated with the exponential-phase RpoS
      level. SIGNIFICANCE AND IMPACT OF THE STUDY: Results from this study define the
      variability in growth and survival of STEC strains that will be useful defining
      food product formulations and process interventions to control STEC. The presence
      of exponential phase sigma(s) expands the significance of this alternative sigma
      factor.

PMID- 22998675
TI  - Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and
      cell delivery systems: present status and applications.
AB  - Alginate is a non-toxic, biocompatible and biodegradable natural polymer with a
      number of peculiar physicochemical properties for which it has wide applications
      in drug delivery and cell delivery systems. Hydrogel formation can be obtained by
      interactions of anionic alginates with multivalent inorganic cations by simple
      ionotropic gelation method. Hydrophilic polymeric network of three dimensional
      cross linked structures of hydrogels absorb substantial amount of water or
      biological fluids. Among the numerous biomaterials used for hydrogel formation
      alginate has been and will continue to be one of the most important biomaterial.
      Therefore, in view of the vast literature support, we focus in this review on
      alginate - based hydrogel as drug delivery and cell delivery carriers for
      biomedical applications. Various properties of alginates, their hydrogels and
      also various techniques used for preparing alginate hydrogels have been reviewed.

PMID- 22998676
TI  - Topoisomerase II-mediated DNA cleavage and mutagenesis activated by nitric oxide
      underlie the inflammation-associated tumorigenesis.
AB  - AIMS: Both cancer-suppressing and cancer-promoting properties of reactive
      nitrogen and oxygen species (RNOS) have been suggested to play a role in tumor
      pathology, particularly those activities associated with chronic inflammation.
      Here, we address the impact of nitric oxide (NO) on the induction of DNA damage
      and genome instability with a specific focus on the involvement of topoisomerase
      II (TOP2). We also investigate the contribution of NO to the formation of skin
      melanoma in mice. RESULTS: Similar to the TOP2-targeting drug, etoposide (VP-16),
      the NO-donor, S-nitrosoglutathione (GSNO), induces skin melanomas formation in
      7,12-dimethyl- benz[a]anthracene (DMBA)-initiated mice. To explore the
      mechanism(s) underlying this NO-induced tumorigenesis, we use a co-culture model
      system to demonstrate that inflamed macrophages with inducible NO synthase (iNOS)
      expression cause gamma-H2AX activation, p53 phosphorylation, and chromosome DNA
      breaks in the target cells. Inhibitor experiments revealed that NO and TOP2
      isozymes are responsible for the above described cellular phenotypes. Notably,
      NO, unlike VP-16, preferentially induces the formation of TOP2beta cleavable
      complexes (TOP2betacc) in cells. Moreover, GSNO induced TOP2-dependent DNA
      sequence rearrangements and cytotoxicity. Furthermore, the incidences of GSNO-
      and VP-16-induced skin melanomas were also observed to be lower in the skin
      specific top2beta-knockout mice. Our results suggest that TOP2 isozymes
      contribute to NO-induced mutagenesis and subsequent cancer development during
      chronic inflammation. INNOVATION AND CONCLUSIONS: We provide the first
      experimental evidence for the functional role of TOP2 in NO-caused DNA damage,
      mutagenesis, and carcinogenesis. Notably, these studies contribute to our
      molecular understanding of the cancer-promoting actions of RNOS during chronic
      inflammation.

PMID- 22998677
TI  - Polyamines affect the cellular growth and structure of pro-embryogenic masses in
      Araucaria angustifolia embryogenic cultures through the modulation of proton pump
      activities and endogenous levels of polyamines.
AB  - Polyamines (PAs) are abundant polycationic compounds involved in many
      physiological processes in plants, including somatic embryogenesis. This study
      investigates the role of PAs on cellular growth and structure of pro-embryogenic
      masses (PEMs), endogenous PA and proton pump activities in embryogenic suspension
      cultures of Araucaria angustifolia. The embryogenic suspension cultures were
      incubated with putrescine (Put), spermidine (Spd), spermine (Spm) and the
      inhibitor methylglyoxal-bis(guanylhydrazone) (MGBG), respectively (1 mM). After
      24 h and 21 days, the cellular growth and structure of PEMs, endogenous PA
      contents and proton pump activities were analyzed. The addition of Spm reduced
      the cellular growth and promoted the development of PEMs in embryogenic cultures,
      which could be associated with a reduction in the activities of proton pumps,
      such as H(+) -ATPase P- and V-types and H(+) -PPases, and alterations in the
      endogenous PA contents. Spm significantly affected the physiology of the A.
      angustifolia somatic embryogenesis suspension, as it potentially affects cellular
      growth and structure of PEMs through the modulation of proton pump activities.
      This work demonstrates the involvement of exogenous PAs in the modulation of
      cellular growth and structure of PEMs, endogenous PA levels and proton pump
      activities during somatic embryogenesis. To our knowledge, this study is the
      first to report a relationship between PAs and proton pump activities in these
      processes. The results obtained in this study offer new perspectives for studies
      addressing the role of PAs and proton pump on somatic embryogenesis in this
      species.

PMID- 22998678
TI  - Increased risk of erectile dysfunction among males with central serous
      chorioretinopathy -- a retrospective cohort study.
AB  - PURPOSE: Central serous chorioretinopathy (CSCR) mostly affects middle-aged men
      and has been associated with stress and hypercortisolism. We hypothesized that
      some factors prone to inducing CSCR could also have a harmful effect on erectile
      function. This study aimed to investigate the risk of subsequent erectile
      dysfunction after CSCR using Taiwan National Health Insurance Research Database.
      METHODS: The study cohort (n = 1220) consisted of newly diagnosed CSCR men aged
      19-64 years between 1999 and 2007, and men matched for age, monthly income and
      time of enrolment were randomly selected as the control group (n = 10870). Cox
      proportional hazard regressions were performed to calculate the hazard ratios
      (HR) of clinically diagnosed erectile dysfunction (including organic origin
      and/or psychogenic origin) for the two groups. Erectile dysfunction-free survival
      analysis was assessed using a Kaplan-Meier method. RESULTS: Twenty-five patients
      (2.0%) from the CSCR cohort and 103 (0.9%) from the control group were diagnosed
      erectile dysfunction clinically during a mean observation period of 4.3 years.
      Patients with CSCR had a significantly higher incidence of erectile dysfunction
      diagnosis than those without CSCR (p < 0.001). After adjusting for age,
      geographic location, chronic comorbidities and medication habits, patients with
      CSCR were found to have a 2.22-fold [95% confidence interval (CI), 1.42-3.46]
      higher hazard ratio of a subsequent erectile dysfunction diagnosis than the
      matched controls. The adjusted HR for organic and psychogenic erectile
      dysfunction were 2.14 (95% CI: 1.34-3.44) and 3.83 (95% CI: 1.47-10.01),
      respectively. CONCLUSIONS: Central serous chorioretinopathy was independently
      associated with an increased risk of being diagnosed with erectile dysfunction.

PMID- 22998679
TI  - Nurses' attitudes towards physical activity care among older people.
AB  - AIMS AND OBJECTIVES: To understand nurses' attitudes towards physical activity
      care for older people in long-term care facilities. BACKGROUND: In long-term care
      facilities, a common approach to daily physical activity is based on the
      identifiable portions of daily life during which the activity occurs. However,
      older people are at risk of falling when they perform daily physical activities.
      Nurses are the first-line caregivers. What nurses' think and do regarding older
      people's participation in daily physical activities in long-term care facilities
      is very important in terms of the clinical decision-making regarding older
      people's physical activity care. DESIGN: An exploratory qualitative design.
      METHODS: Twenty nurses with more than three years of clinical experience from 13
      long-term care facilities located in northern Taiwan were sampled purposively.
      Data were collected though semi-structured interviews. The constant comparative
      data analysis method was used throughout the research. RESULTS: Five themes
      emerged from the data analysis: 'recognising the importance of participation in
      daily physical activity', 'encouraging participation in physical activity',
      'respecting the autonomy of the residents regarding participation in physical
      activity', 'preventing falls' and 'facing a dilemma'. CONCLUSIONS: This study
      identifies that there is a conflict between the nurses' perceptions of the
      residents' daily physical activities, the risk of falls and encouraging greater
      independence. The majority of staff employed in long-term care facilities is
      nursing personnel, and it is these nurses who have the most contact with the
      residents. It is therefore believed that nurses can make the greatest difference
      to the residents' lives and support the quality of care if they can resolve this
      conflict. Relevance to clinical practice.  The results suggest the need to
      increase the nurses' knowledge base regarding the benefits of physical activity
      and also highlight the potentially adverse effect of restraint usage by nurses.

PMID- 22998680
TI  - Executive attention impairment in first-episode schizophrenia.
AB  - BACKGROUND: We compared the attention abilities of a group of first-episode
      schizophrenia (FES) patients and a group of healthy participants using the
      Attention Network Test (ANT), a standard procedure that estimates the functional
      state of three neural networks controlling the efficiency of three different
      attentional behaviors, i.e., alerting (achieving and maintaining a state of high
      sensitivity to incoming stimuli), orienting (ability to select information from
      sensory input), and executive attention (mechanisms for resolving conflict among
      thoughts, feelings, and actions). METHODS: We evaluated 22 FES patients from 17
      to 29 years of age with a recent history of a single psychotic episode treated
      only with atypical neuroleptics, and 20 healthy persons matched with FES patients
      by sex, age, and educational level as the control group. Attention was estimated
      using the ANT in which participants indicate whether a central horizontal arrow
      is pointing to the left or the right. The central arrow may be preceded by
      spatial or temporal cues denoting where and when the arrow will appear, and may
      be flanked by other arrows (hereafter, flankers) pointing in the same or the
      opposite direction. RESULTS: The efficiency of the alerting, orienting, and
      executive networks was estimated by measuring how reaction time was influenced by
      congruency between temporal, spatial, and flanker cues. We found that the control
      group only demonstrated significantly greater attention efficiency than FES
      patients in the executive attention network. CONCLUSIONS: FES patients are
      impaired in executive attention but not in alerting or orienting attention,
      suggesting that executive attention deficit may be a primary impairment during
      the progression of the disease.

PMID- 22998681
TI  - Taxonomic identification of Macrolophus pygmaeus and Macrolophus melanotoma based
      on morphometry and molecular markers.
AB  - Two Macrolophus species, M. melanotoma (=M. caliginosus) and M. pygmaeus, have
      been referred to as efficient predators of several key pests on vegetable crops
      in Europe. However, due to the great morphological similarity of these species,
      they have been confused, with important consequences for inoculative releases of
      these predators in greenhouses and for the conservation of their natural
      populations on greenhouse and outdoor crops. In this work, we developed tools to
      identify these morphologically very similar species. We first confirmed the
      specific status of two Macrolophus populations collected on their respective host
      plants (Dittrichia viscosa and tomato) through crossing experiments. Then, using
      multivariate morphometric analysis, we proposed a linear discriminant function
      that combines head measurements separating males from the two species without
      error. Finally, we designed specific primers for a mitochondrial DNA region that
      were able to distinguish field-collected Macrolophus individuals through
      conventional PCR. In conclusion, the tools developed in the present study will
      allow reliable identification of the Macrolophus species present in crops and in
      the native flora that are the source of populations that colonise them. They will
      also allow correct identification of mass reared Macrolophus to be introduced in
      greenhouse crops in inoculative releases.

PMID- 22998682
TI  - District health executives in Midlands province, Zimbabwe: are they performing as
      expected?
AB  - BACKGROUND: The cornerstone of the health system in Zimbabwe, the district health
      system has been under the responsibility of the district health executive since
      1984. Preliminary information obtained from some provincial health managers in
      Midlands Province suggested a poor performance by most district health
      executives. We therefore investigated the reasons for this poor performance.
      METHODS: A descriptive cross sectional study was conducted. Structured
      interviewer administered questionnaires were used to obtain information from
      district health managers of five randomly selected districts in the province.
      Checklists were used to assess resource availability, staffing levels and proxy
      indicators to effective district health executive function. Data were analysed
      using Epi Info statistical package. RESULTS: Thirty district health managers were
      interviewed. Almost half of the participants could not list at least five
      functions of district health executives. Twenty nine managers reported having
      inadequate management skills requiring training. District health executives
      failed to meet their targets on expected activities in the year 2010 such as
      conducting monthly district health executive meetings, conducting quarterly
      supervision to health centres and submitting quarterly district health reports to
      the provincial level. CONCLUSION: Poor knowledge on expected functions could have
      resulted in poor performance. Without adequate management training district
      health managers are likely to underperform their duties. DHE guidelines were
      therefore distributed to all districts. Management trainings were conducted to
      all district health executives throughout the country from November 2011.

PMID- 22998684
TI  - Health care reform and the road ahead for gastroenterology.

PMID- 22998685
TI  - Association between obesity measured by different parameters and severity of
      psoriasis.
AB  - BACKGROUND: Obesity has been associated with the severity of psoriasis, but this
      relationship is not completely understood. OBJECTIVES: This study aimed to
      evaluate associations between the severity of psoriasis and weight excess as
      determined using a variety of parameters. METHODS: A cross-sectional study was
      performed in 296 psoriasis patients. Their body mass index (BMI), waist
      circumference (WC), and waist : hip ratio (WHR) values were compared with results
      on a psoriasis area severity index (PASI). RESULTS: The frequency of severe
      psoriasis was higher in men (P < 0.05). Direct correlations were established
      between PASI scores and each of BMI (R = 0.0154, P = 0.01), WC (R = 0.207, P =
      0.001), and WHR (R = 0.164, P = 0.007). CONCLUSIONS: This study extends previous
      reports of an association between psoriasis and obesity and shows a direct
      correlation between obesity as measured according to different parameters and
      psoriasis severity.

PMID- 22998683
TI  - Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes
      in Schimke immuno-osseous dysplasia?
AB  - BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke
      immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic
      mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent
      regulator of chromatin, subfamily a-like 1). However, the mechanism by which the
      vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We
      reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and
      immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD
      patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3
      of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal
      and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and
      disorganized elastin fibers, and the pulmonary disease was characterized by
      panlobular enlargement of air spaces. Consistent with a cell autonomous disorder,
      SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung
      of SIOD patients had reduced expression of elastin and alterations in the
      expression of regulators of elastin gene expression. CONCLUSIONS: This first
      comprehensive study of the vascular and pulmonary complications of SIOD shows
      that these commonly cause morbidity and mortality and might arise from impaired
      elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin
      expression provides a model for understanding other features of SIOD.

PMID- 22998686
TI  - Allergen specificity is relevant for immunotherapy prescription in polysensitised
      children.
AB  - The sensitization to more allergens, such as polysenitization, is becoming a
      frequent characteristic of allergic patients, since the childhood. However, this
      phenomenon is considered an obstacle to prescribe immunotherapy by many doctors.
      This study investigated the relevance of polysensitization in a cohort of
      allergic children and evaluated the number of allergen extracts prescribed for
      these children. There are allergens that are frequent, but not prescribed. This
      issue should be matter of adequate debate for Italian paediatricians.

PMID- 22998688
TI  - Small body size increases the regional differentiation of populations of tropical
      mantellid frogs (Anura: Mantellidae).
AB  - The processes affecting species diversification may also exert an influence on
      patterns of genetic variability within species. We evaluated the contributions of
      five variables potentially influencing clade diversification (body size,
      reproductive mode, range size, microhabitat and skin texture) on mtDNA divergence
      and polymorphism among populations of 40 species of frogs (Mantellidae) from two
      rainforest communities in Madagascar. We report an inverse association between
      body size and nucleotide divergence between populations but find no influence of
      other variables on genetic variation. Body size explained ca. 11% of the
      variation in nucleotide divergence between populations and was coupled with high
      F(ST)  levels and an absence of haplotype sharing in small-bodied and medium
      sized frogs. Low dispersal ability is likely the proximate mechanism producing
      higher population differentiation in small mantellids. The lack of genetic
      cohesion among populations establishes regional genetic fragmentation which in
      turn has the potential to accelerate rates of allopatric speciation in small
      frogs relative to large species. However, there is little evidence of increased
      speciation rates in these or other small-bodied organisms. We reconcile these
      contradictory observations by suggesting that lower dispersal ability also curbs
      colonization of new areas, decelerating diversification in weak dispersers. Our
      results imply that the intermediate dispersal model also applies to amphibians
      and may explain inconsistent previous results on the correlation of body size and
      speciation rate.

PMID- 22998687
TI  - Gastric exocrine and endocrine cell morphology under prolonged acid inhibition
      therapy: results of a 5-year follow-up in the LOTUS trial.
AB  - BACKGROUND: Sustained acid inhibition with PPI stimulates gastrin secretion,
      exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the
      oxyntic mucosa. It may also accelerate development of gastric gland atrophy in
      Helicobacter pylori-infected individuals. AIMS: To evaluate gastric exocrine and
      endocrine cell changes in GERD patients randomised to laparoscopic antireflux
      surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n =
      266). METHODS: Antral and corpus biopsies were taken at endoscopy and serum
      gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5
      years' therapy. RESULTS: Biopsies were available at each time point for 158 LARS
      patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal
      inflammation and activity improved significantly (P < 0.001) and stabilised after
      3 years on esomeprazole while no change in inflammation was observed after LARS.
      Oxyntic mucosal inflammation and activity remained stable on esomeprazole but
      decreased slightly over time after LARS. Neither intestinal metaplasia nor
      atrophy developed in the oxyntic mucosa. ECL cell density increased significantly
      after ESO (P < 0.001), corresponding with an increase in circulating gastrin and
      chromogranin A. After LARS, there was a significant decrease in ECL cell density
      (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin.
      CONCLUSIONS: Antral gastritis improved in H. pylori-infected GERD patients after
      5 years on esomeprazole, with little change in laparoscopic antireflux surgery
      patients, who acted as a control. Despite a continued proliferative drive on
      enterochromaffin-like cells during esomeprazole treatment, no dysplastic or
      neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

PMID- 22998690
TI  - A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive
      status epilepticus induced by unilateral intrahippocampal injection of kainic
      acid.
AB  - PURPOSE:   Models of temporal lobe epilepsy are commonly utilized to study focal
      epileptogenesis and ictogenesis. The criteria that define animal models
      representative of human mesial temporal lobe may vary in different laboratories.
      We describe herein a focal epilepsy model of mesial temporal (hippocampal) origin
      that relies on the analysis of interictal and ictal electroencephalography (EEG)
      patterns and on their correlation with seizure symptoms and neuropathologic
      findings. The study is based on guinea pigs, a species seldom utilized to develop
      chronic epilepsy models. METHODS:   Young adult guinea pigs were bilaterally
      implanted under isoflurane anesthesia with epidural electrodes over somatosensory
      cortex and depth electrodes in CA1 hippocampal region. A stainless steel guide
      cannula was positioned unilaterally in the right dorsal hippocampus to inject 1
      MUl of 0.9% NaCl solution containing 1 MUg kainic acid (KA). One week after
      surgery, continuous 24 h/day video-EEG monitoring was performed 48 h before and
      every other week after KA injection, for no <1 month. EEG data were recorded wide
      band at 2 kHz. After video-EEG monitoring, brains were analyzed for thionine and
      Timm staining and glial fibrillary acid protein (GFAP) immunostaining. KEY
      FINDINGS:   Unilateral injection of KA in dorsal hippocampus of guinea pigs
      induces an acute nonconvulsive status epilepticus (SE) that terminates within 24
      h (n = 22). Chronic seizures with very mild motor signs (undetectable without EEG
      monitoring) and highly variable recurrence patterns appear in 45.5% (10 of 22) KA
      treated animals, with variable delays from the initial SE. In these animals
      interictal events, CA1 cell loss, gliosis, and altered Timm staining pattern were
      observed. The induction of a chronic condition did not correlate with the
      duration of the nonconvulsive acute SE, but correlated with the extension and
      quality of neuropathologic damage. SIGNIFICANCE:   We demonstrate that a model of
      hippocampal (mesial temporal lobe) epilepsy can be developed in the guinea pig by
      intrahippocampal injection of KA. Seizure events in this model show little
      behavioral signs and may be overlooked without extensive video-EEG monitoring.
      The establishment of a chronic epileptic condition correlates with the extension
      of the hippocampal damage (mainly cell loss and gliosis) and not with the
      intensity of the initial SE.

PMID- 22998689
TI  - Prevention of hypoglycemia-induced neuronal death by minocycline.
AB  - Diabetic patients who attempt strict management of blood glucose levels
      frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes
      neuronal death and cognitive impairment. There is no effective tool for
      prevention of these unwanted clinical sequelae. Minocycline, a second-generation
      tetracycline derivative, has been recognized as an anti-inflammatory and
      neuroprotective agent in several animal models such as stroke and traumatic brain
      injury. In the present study, we tested whether minocycline also has protective
      effects on hypoglycemia-induced neuronal death and cognitive impairment. To test
      our hypothesis we used an animal model of insulin-induced acute hypoglycemia.
      Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose
      reperfusion and injected once per day for the following 1 week. Histological
      evaluation for neuronal death and microglial activation was performed from 1 day
      to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after
      hypoglycemia. Microglial activation began to be evident in the hippocampal area
      at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection
      significantly reduced hypoglycemia-induced microglial activation and
      myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced
      by minocycline treatment when evaluated at 1 week after hypoglycemia.
      Hypoglycemia-induced cognitive impairment is also significantly prevented by the
      same minocycline regimen when subjects were evaluated at 6 weeks after
      hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours
      post-insult) with minocycline protects against microglial activation, neuronal
      death and cognitive impairment caused by severe hypoglycemia. The present study
      suggests that minocycline has therapeutic potential to prevent hypoglycemia
      induced brain injury in diabetic patients.

PMID- 22998691
TI  - Work limitations and their relationship to morbidity burden among academic health
      center employees with diabetes.
AB  - The objective of this study was to determine the prevalence of work limitations
      and their relationship to morbidity burden among academic health center employees
      with diabetes. Employees with diabetes were surveyed via Internet and mail using
      the Work Limitations Questionnaire. Morbidity burden was measured using the
      Adjusted Clinical Groups methodology. Seventy-two percent of the employees with
      diabetes had a work limitation. Adjusted odds ratios for overall, physical, time,
      and output limitations were 1.81, 2.27, 2.13, and 2.14, respectively. Morbidity
      burden level is an indicator of work limitations in employees with diabetes and
      can be used to identify employees who may benefit from specialized services aimed
      at addressing their work limitations associated with diabetes.

PMID- 22998692
TI  - Occupational injuries for consecutive and cumulative shifts among hospital
      registered nurses and patient care associates: a case-control study.
AB  - Nontraditional work shifts for hospital registered nurses and patient care
      associates and associated injuries were examined through a case-control study.
      Inpatient care requires that many staff work nontraditional shifts, including
      nights and 12-hour shifts, but some characteristics remain unexplored, especially
      consecutive shifts. A total of 502 cases (injured workers) were matched to single
      controls based on their hospital, unit type, job type, gender, and age (+/- 5
      years). Conditional logistic regression was used for the analysis, controlling
      for weekly hours scheduled. For both, consecutive shifts of 2 or more days and
      some various cumulative shifts over a week and month period, especially night
      shifts, were associated with increased odds of injury. More investigations on the
      phenomenon of consecutive shifts are recommended. Additionally, the assessment of
      shift policy and subsequent injury outcomes is necessary before implementing
      intervention strategies.

PMID- 22998694
TI  - Safety of erythropoiesis-stimulating agents in patients with end-stage kidney
      disease: data are safer than extrapolations.

PMID- 22998695
TI  - Surgical outcomes and opportunities.

PMID- 22998696
TI  - Acute care in the NHS: adapt or bust.

PMID- 22998693
TI  - Lack of Csk-mediated negative regulation in a unicellular SRC kinase.
AB  - Phosphotyrosine-based signaling plays a vital role in cellular communication in
      multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest
      phylogenetic group to metazoans) possess numbers of tyrosine kinases that are
      comparable to those in complex metazoans. Here, we have characterized tyrosine
      kinases from the filasterean Capsaspora owczarzaki, a unicellular protist
      representing the sister group to choanoflagellates and metazoans. Two Src-like
      tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both
      of which have the arrangement of SH3, SH2, and catalytic domains seen in
      mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to
      punctate structures in filopodia that may represent primordial focal adhesions.
      We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are
      active tyrosine kinases. Mammalian Src kinases are normally regulated in a
      reciprocal fashion by autophosphorylation in the activation loop (which increases
      activity) and by Csk-mediated phosphorylation of the C-terminal tail (which
      inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of
      CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We
      have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We
      cloned, expressed, and purified CoCsk and found that it has no measurable
      tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate
      CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in
      Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src
      family kinases appears to have arisen with the emergence of metazoans.

PMID- 22998697
TI  - NCDs and the UN: danger of a missed opportunity.

PMID- 22998698
TI  - Towards a maturation of trauma research.

PMID- 22998699
TI  - What factors affect mortality after surgery?

PMID- 22998700
TI  - Should intravenous catheters be replaced routinely?

PMID- 22998701
TI  - Perioperative mortality in developed and developing countries.

PMID- 22998703
TI  - Russell Gruen: precision and progress in trauma care.

PMID- 22998704
TI  - Thrombolysis in acute ischaemic stroke.

PMID- 22998705
TI  - Thrombolysis in acute ischaemic stroke.

PMID- 22998706
TI  - Thrombolysis in acute ischaemic stroke.

PMID- 22998707
TI  - Thrombolysis in acute ischaemic stroke.

PMID- 22998709
TI  - Thrombolysis in acute ischaemic stroke.

PMID- 22998710
TI  - Antipsychotic drugs for relapse prevention in schizophrenia.

PMID- 22998711
TI  - The Irish health system and the economic crisis.

PMID- 22998713
TI  - Latin American medical journals indexed by Thomson ISI.

PMID- 22998714
TI  - Plus ca change, plus c'est la meme chose.

PMID- 22998717
TI  - Perioperative and anaesthetic-related mortality in developed and developing
      countries: a systematic review and meta-analysis.
AB  - BACKGROUND: The magnitude of risk of death related to surgery and anaesthesia is
      not well understood. We aimed to assess whether the risk of perioperative and
      anaesthetic-related mortality has decreased over the past five decades and
      whether rates of decline have been comparable in developed and developing
      countries. METHODS: We did a systematic review to identify all studies published
      up to February, 2011, in any language, with a sample size of over 3000 that
      reported perioperative mortality across a mixed surgical population who had
      undergone general anaesthesia. Using standard forms, two authors independently
      identified studies for inclusion and extracted information on rates of
      anaesthetic-related mortality, perioperative mortality, cardiac arrest, American
      Society of Anesthesiologists (ASA) physical status, geographic location, human
      development index (HDI), and year. The primary outcome was anaesthetic sole
      mortality. Secondary outcomes were anaesthetic contributory mortality, total
      perioperative mortality, and cardiac arrest. Meta-regression was done to
      ascertain weighted event rates for the outcomes. FINDINGS: 87 studies met the
      inclusion criteria, within which there were more than 21.4 million anaesthetic
      administrations given to patients undergoing general anaesthesia for surgery.
      Mortality solely attributable to anaesthesia declined over time, from 357 per
      million (95% CI 324-394) before the 1970s to 52 per million (42-64) in the 1970s
      80s, and 34 per million (29-39) in the 1990s-2000s (p<0.00001). Total
      perioperative mortality decreased over time, from 10,603 per million (95% CI
      10,423-10,784) before the 1970s, to 4533 per million (4405-4664) in the 1970s
      80s, and 1176 per million (1148-1205) in the 1990s-2000s (p<0.0001). Meta
      regression showed a significant relation between risk of perioperative and
      anaesthetic-related mortality and HDI (all p<0.00001). Baseline risk status of
      patients who presented for surgery as shown by the ASA score increased over the
      decades (p<0.0001). INTERPRETATION: Despite increasing patient baseline risk,
      perioperative mortality has declined significantly over the past 50 years, with
      the greatest decline in developed countries. Global priority should be given to
      reducing total perioperative and anaesthetic-related mortality by evidence-based
      best practice in developing countries. FUNDING: University of Western Ontario.

PMID- 22998716
TI  - Routine versus clinically indicated replacement of peripheral intravenous
      catheters: a randomised controlled equivalence trial.
AB  - BACKGROUND: The millions of peripheral intravenous catheters used each year are
      recommended for 72-96 h replacement in adults. This routine replacement increases
      health-care costs and staff workload and requires patients to undergo repeated
      invasive procedures. The effectiveness of the practice is not well established.
      Our hypothesis was that clinically indicated catheter replacement is of equal
      benefit to routine replacement. METHODS: This multicentre, randomised, non
      blinded equivalence trial recruited adults (>=18 years) with an intravenous
      catheter of expected use longer than 4 days from three hospitals in Queensland,
      Australia, between May 20, 2008, and Sept 9, 2009. Computer-generated random
      assignment (1:1 ratio, no blocking, stratified by hospital, concealed before
      allocation) was to clinically indicated replacement, or third daily routine
      replacement. Patients, clinical staff, and research nurses could not be masked
      after treatment allocation because of the nature of the intervention. The primary
      outcome was phlebitis during catheterisation or within 48 h after removal. The
      equivalence margin was set at 3%. Primary analysis was by intention to treat.
      Secondary endpoints were catheter-related bloodstream and local infections, all
      bloodstream infections, catheter tip colonisation, infusion failure, catheter
      numbers used, therapy duration, mortality, and costs. This trial is registered
      with the Australian New Zealand Clinical Trials Registry, number
      ACTRN12608000445370. FINDINGS: All 3283 patients randomised (5907 catheters) were
      included in our analysis (1593 clinically indicated; 1690 routine replacement).
      Mean dwell time for catheters in situ on day 3 was 99 h (SD 54) when replaced as
      clinically indicated and 70 h (13) when routinely replaced. Phlebitis occurred in
      114 of 1593 (7%) patients in the clinically indicated group and in 114 of 1690
      (7%) patients in the routine replacement group, an absolute risk difference of
      0.41% (95% CI -1.33 to 2.15%), which was within the prespecified 3% equivalence
      margin. No serious adverse events related to study interventions occurred.
      INTERPRETATION: Peripheral intravenous catheters can be removed as clinically
      indicated; this policy will avoid millions of catheter insertions, associated
      discomfort, and substantial costs in both equipment and staff workload. Ongoing
      close monitoring should continue with timely treatment cessation and prompt
      removal for complications. FUNDING: Australian National Health and Medical
      Research Council.

PMID- 22998718
TI  - Early management of severe traumatic brain injury.
AB  - Severe traumatic brain injury remains a major health-care problem worldwide.
      Although major progress has been made in understanding of the pathophysiology of
      this injury, this has not yet led to substantial improvements in outcome. In this
      report, we address present knowledge and its limitations, research innovations,
      and clinical implications. Improved outcomes for patients with severe traumatic
      brain injury could result from progress in pharmacological and other treatments,
      neural repair and regeneration, optimisation of surgical indications and
      techniques, and combination and individually targeted treatments. Expanded
      classification of traumatic brain injury and innovations in research design will
      underpin these advances. We are optimistic that further gains in outcome for
      patients with severe traumatic brain injury will be achieved in the next decade.

PMID- 22998719
TI  - Haemorrhage control in severely injured patients.
AB  - Most surgeons have adopted damage control surgery for severely injured patients,
      in which the initial operation is abbreviated after control of bleeding and
      contamination to allow ongoing resuscitation in the intensive-care unit.
      Developments in early resuscitation that emphasise rapid control of bleeding,
      restrictive volume replacement, and prevention or early management of
      coagulopathy are making definitive surgery during the first operation possible
      for many patients. Improved topical haemostatic agents and interventional
      radiology are becoming increasingly useful adjuncts to surgical control of
      bleeding. Better understanding of trauma-induced coagulopathy is paving the way
      for the replacement of blind, unguided protocols for blood component therapy with
      systemic treatments targeting specific deficiencies in coagulation. Similarly,
      treatments targeting dysregulated inflammatory responses to severe injury are
      under investigation. As point-of-care diagnostics become more suited to emergency
      environments, timely targeted intervention for haemorrhage control will result in
      better patient outcomes and reduced demand for blood products. Our Series paper
      describes how our understanding of the roles of the microcirculation,
      inflammation, and coagulation has shaped new and emerging treatment strategies.

PMID- 22998720
TI  - Advances and future directions for management of trauma patients with
      musculoskeletal injuries.
AB  - Musculoskeletal injuries are the most common reason for operative procedures in
      severely injured patients and are major determinants of functional outcomes. In
      this paper, we summarise advances and future directions for management of
      multiply injured patients with major musculoskeletal trauma. Improved
      understanding of fracture healing has created new possibilities for management of
      particularly challenging problems, such as delayed union and non union of
      fractures and large bone defects. Optimum timing of major orthopaedic
      interventions is guided by increased knowledge about the immune response after
      injury. Individual treatment should be guided by trading off the benefits of
      early definitive skeletal stabilisation, and the potentially life-threatening
      risks of systemic complications such as fat embolism, acute lung injury, and
      multiple organ failure. New methods for measurement of fracture healing and
      function and quality of life outcomes pave the way for landmark trials that will
      guide the future management of musculoskeletal injuries.

PMID- 22998721
TI  - Travel and fake artesunate: a risky business.

PMID- 22998722
TI  - The effect of endotracheal tube size on voice and swallowing function in patients
      with thermal burn injury: an evaluation using the Australian Therapy Outcome
      Measures (AusTOMS).
AB  - The objective of this study was to determine if intubation using larger
      endotracheal tube sizes in mechanically ventilated patients with thermal burn
      injury adversely affects voice and swallowing function. This prospective,
      observational study was conducted in patients with thermal burn injuries, who
      were mechanically ventilated via an endotracheal tube. The primary outcome
      measures were changes in voice and swallowing function, assessed using the
      Australian Therapy Outcome Measures (AusTOMS), immediately before the burn
      injury, and 12 months after the removal of the endotracheal tube. Of 101 patients
      screened, 20 male patients were followed for 12 months. Patients intubated with
      size 8.0 or larger endotracheal tubes were compared to patients with size 7.5
      endotracheal tubes or smaller. Patients with the larger endotracheal tubes had a
      significant 1.8-point (9%) decline in their AusTOMS voice score (p =.01) using
      the paired t-test, but there was no significant difference between the two groups
      using the independent samples t-test. There was no significant difference in
      swallowing outcome between the two groups. Male patients with thermal burn
      injuries, mechanically ventilated using size 8.0 endotracheal tubes or larger,
      had a statistically significant decline in voice outcome; however, interpretation
      of this result is limited by methodological considerations.

PMID- 22998724
TI  - Peritoneovenous shunting for refractory ascites results in worsening of nephrotic
      syndrome.
AB  - Peritoneovenous shunt (PVS) is accepted as a treatment for refractory ascites due
      to liver cirrhosis. Infection is a well-known complication of shunting. However,
      the effects of PVS in terms of complications for renal disease are unclear. We
      encountered a case involving a 52-year-old man with alcoholic liver cirrhosis and
      complications of nephrotic syndrome that were worsened by PVS. He received PVS
      for refractory ascites due to alcoholic liver cirrhosis before coming to our
      hospital for evaluation for liver transplantation. Nephrotic syndrome was then
      identified due to cirrhosis-related membranoproliferative glomerulonephritis
      (MPGN). Prednisolone was administrated at 60 mg/day for MPGN. On day 5, he showed
      grade IV hepatic encephalopathy (West Haven criteria). Tapering prednisolone and
      intestinal cleansing with lactulose treatment improved hepatic encephalopathy,
      but hyperammonemia persisted and the PVS was removed. After shunt removal,
      urinary protein levels decreased from 4-6 g/day to 0.3-0.5 g/day and ammonia
      levels decreased. PVS may increase the excretion of urinary protein and increase
      ammonia levels in patients with complications of glomerulonephritis.

PMID- 22998723
TI  - High glucose mediates endothelial-to-chondrocyte transition in human aortic
      endothelial cells.
AB  - BACKGROUND: Vascular calcification is one of the common complications in diabetes
      mellitus. Many studies have shown that high glucose (HG) caused cardiovascular
      calcification, but its underlying mechanism is not fully understood. Recently,
      medial calcification has been most commonly described in the vessels of patients
      with diabetes. Chondrocytes were involved in the medial calcification. Recent
      studies have shown that the conversion into mesenchymal stem cells (MSCs) via the
      endothelial-to-mesenchymal transition (EndMT) could be triggered in chondrocytes.
      Our previous research has indicated that HG induced EndMT in human aortic
      endothelial cells (HAECs). Therefore, we addressed the question of whether HG
      induced EndMT could be transitioned into MSCs and differentiated into
      chondrocytes. METHODS: HAECs were divided into three groups: a normal glucose
      (NG) group, HG group (30 mmol/L), and mannitol (5.5 mmol/L NG + 24.5 mmol/L)
      group. Pathological changes were investigated using fluorescence microscopy and
      electron microscopy. Immunofluorescence staining was performed to detect the co
      expression of endothelial markers, such as CD31, and fibroblast markers, such as
      fibroblast-specific protein 1 (FSP-1). The expression of FSP-1 was detected by
      real time-PCR and western blots. Endothelial-derived MSCs were grown in MSC
      medium for one week. The expression of the MSCs markers STRO-1, CD44, CD10 and
      the chondrocyte marker SOX9 was detected by immunofluorescence staining and
      western blots. Chondrocyte expression was detected by alcian blue staining.
      Calcium deposits were analyzed by alizarin red staining. RESULTS: The incubation
      of HAECs exposed to HG resulted in a fibroblast-like phenotype. Double staining
      of the HAECs indicated a co-localization of CD31 and FSP-1. The expression of FSP
      1 was significantly increased in the HG group, and the cells undergoing EndMT
      also expressed STRO-1, CD44 and SOX9 compared with the controls (P < 0.05).
      Additionally, alcian blue staining in the HG group was positive compared to the
      NG group. Consistent with the evaluation of SOX9 expression, calcium deposits
      analyzed by alizarin red staining were also enhanced by the HG treatment.
      Specifically, we showed that HG-induced EndMT is accompanied by the activation of
      the canonical Snail pathway. CONCLUSIONS: Our study demonstrated that HG could
      induce endothelial cells transdifferentiation into chondrocyte-like cells via the
      EndMT, which is mediated in part by the activation of the Snail signaling
      pathway.

PMID- 22998725
TI  - Brassinosteroids accelerate recovery of photosynthetic apparatus from cold stress
      by balancing the electron partitioning, carboxylation and redox homeostasis in
      cucumber.
AB  - The aim of this study was to examine the role of brassinosteroids (BRs) in
      protecting the photosynthetic apparatus from cold-induced damage in cucumber
      (Cucumis sativus) plants. Recovery at both high light (HL) and low light (LL)
      after a cooling at 10/7 degrees C induced irreversible inhibition of CO2
      assimilation, photoinhibition at photosystem I (PSI) and inhibition of enzyme
      activities of Calvin cycle and ascorbate (AsA)-reduced glutathione (GSH) cycle,
      followed by accumulation of H2 O2 and malondialdehyde. However, cold-induced
      photoinhibition at PSII was fully recovered at LL but not at HL. Meanwhile,
      recovery at HL increased electron flux to O2 -dependent alternative pathway
      [Ja(O2 -dependent)]. Foliar application of 24-epibrassinolide (EBR) accelerated
      recovery from photoinhibition of PSII but not of PSI. EBR also significantly
      increased CO2 assimilation, activity of Calvin cycle enzymes and electron flux to
      carbon reduction [Je(PCR)], with a concomitant decrease in Ja(O2 -dependent);
      meanwhile EBR increased the activity of enzymes in AsA-GSH cycle and cellular
      redox states. However, the positive effect of EBR on plant recovery was observed
      only at HL, but not LL. These results indicate that BR accelerates the recovery
      of photosynthetic apparatus at HL by activation of enzymes in Calvin cycle and
      increasing the antioxidant capacity, which in turn mitigate the photooxidative
      stress and the inhibition of plant growth during the recovery.

PMID- 22998726
TI  - Comparative proteomic analysis of casein and whey as prepared by chymosin-induced
      separation, isoelectric precipitation or ultracentrifugation.
AB  - Fractionation of bovine milk was performed using chymosin-induced separation,
      isoelectric precipitation or ultracentrifugation as separation techniques prior
      to gel-based proteomic analysis. This approach allowed for comparative display
      and identification of proteins partitioned into casein and whey, respectively.
      Initially, three different staining methods (silver staining, colloidal Coomassie
      Blue G-250 or fluorescent Flamingo Pink staining) for two-dimensional gel
      electrophoresis (2-DGE) analysis were compared for their suitability as staining
      agent, especially in relation to their suitability to reveal differences in the
      casein fractions. Fluorescent staining proved to be the most appropriate for this
      purpose, giving a high sensitivity, and using this staining method,
      characteristic 2-DGE fingerprints were obtained for each casein and whey fraction
      from each separation method. A number of protein spots in both casein and whey
      fractions varied with separation method and these spots were subsequently
      identified using tandem mass spectrometry (MS). In rennet casein, proteolytic
      fragmentation of caseins (alpha(s1)-, alpha(s2),-, beta- and kappa-) was
      identified as a result of chymosin hydrolysis, whereas the 2-DGE profile of acid
      and ultracentrifuged casein was dominated by the presence of multiple isoforms of
      kappa-caseins. Furthermore, casein remnants were identified in milk serum after
      ultracentrifugation. This study shows that gel-based proteomic analysis is
      suitable for characterisation of subtle variations in protein composition of milk
      fractions that occur as a consequence of different milk fractionation strategies.

PMID- 22998727
TI  - Trigeminal stereotactic electrolysis induces dry eye in mice.

PMID- 22998731
TI  - Why join a neighbour: fitness consequences of colony fusions in termites.
AB  - The evolution of life is characterized by major evolutionary transitions during
      which independent units cooperated and formed a new level of selection.
      Relatedness is a common mechanism that reduces conflict in such cooperative
      associations. One of the latest transitions is the evolution of social insect
      colonies. As expected, they are composed of kin and mechanisms have evolved that
      prevent the intrusion of nonrelatives. Yet, there are exceptions an extreme case
      is the fusion of unrelated colonies. What are the advantages of fusions that have
      colonies with a high potential for conflict as a consequence? Here, we
      investigated fitness costs and benefits of colony fusions in a lower termite
      species, Cryptotermes secundus, in which more than 25% of all colonies in the
      field are fused. We found two benefits of colony fusion depending on colony size:
      very small colonies had an increased probability of survival when they fused, yet
      for most colony sizes mainly a few workers profit from colony fusions as their
      chance to become reproductives increased. This individual benefit was often
      costly for other colony members: colony growth was reduced and the current
      reproductives had an increased chance of dying when fusions were aggressive. Our
      study suggests that fusion of colonies often is the result of 'selfish' worker
      interests to become reproductives, and this might have been important for the
      termites' social evolution. Our results uniquely shows that selfish interests
      among related colony members can lead to the formation of groups with increased
      potential for conflict among less related members.

PMID- 22998730
TI  - The association of leisure-time physical activity and active commuting with
      measures of socioeconomic position in a multiethnic population living in the
      Netherlands: results from the cross-sectional SUNSET study.
AB  - BACKGROUND: In most European origin populations measures of socioeconomic
      position are positively associated with leisure time physical activity (LTPA),
      this is unclear for active commuting. In addition, these associations have
      scarcely been studied in ethnic minority groups, who often have a high
      cardiovascular disease risk. Because of the expected public health potential, we
      assessed the relationship of active commuting and LTPA with measures of
      socioeconomic position across two large ethnic minority groups in the Netherlands
      as compared to the European-Dutch population. METHODS: We included South Asian
      Surinamese (n = 370), African-Surinamese (n = 689), and European-Dutch (n = 567)
      from the cross-sectional population-based SUNSET study (2001-2003). Active
      commuting and LTPA were assessed by the SQUASH physical activity questionnaire
      and calculated in square-root-transformed metabolic equivalents of task
      hours/week (SQRTMET). Socioeconomic position was indicated by level of education
      (low/high) and occupational class (low/high). We used age-adjusted linear
      regression models to assess the association between physical activity and
      socioeconomic position. RESULTS: Compared to the European-Dutch men, South Asian
      Surinamese men engaged in lower levels of commuting activity and LTPA, and South
      Asian-Surinamese women engaged in lower levels of LTPA than their European-Dutch
      counterparts. Differences between the African Surinamese and the European-Dutch
      were small. We observed a positive gradient in active commuting activity for
      education in European-Dutch men (beta high education was 0.93, 95%CI: 0.45-1.40
      SQRTMET higher versus low education), in South Asian-Surinamese men (beta: 0.56,
      0.19-0.92), but not in African-Surinamese men (-0.06, -0.45-0.33, p for ethnicity
      interaction = 0.002). In women we observed a positive gradient in active
      commuting activity and occupational class in European-Dutch women, and less
      strongly in South Asian-Surinamese and African-Surinamese women (p for ethnicity
      interaction = 0.02). For LTPA and socioeconomic position, we observed no
      statistically significant interaction by ethnicity. CONCLUSIONS: The positive
      gradient for socioeconomic position observed in European-Dutch was less strong,
      in particular for active commuting, among the South Asian-Surinamese and the
      African-Surinamese. This indicates that the typical focus on physical activity
      interventions in lower socioeconomic groups could work for European-Dutch
      populations, but this strategy may not be entirely applicable in the ethnic
      minority groups.

PMID- 22998728
TI  - Macroautophagy deficiency mediates age-dependent neurodegeneration through a
      phospho-tau pathway.
AB  - BACKGROUND: Macroautophagy is an evolutionarily conserved mechanism for bulk
      intracellular degradation of proteins and organelles. Pathological studies have
      implicated macroautophagy defects in human neurodegenerative disorders of aging
      including Alzheimer's disease and tauopathies. Neuronal deficiency of
      macroautophagy throughout mouse embryonic development results in
      neurodevelopmental defects and early postnatal mortality. However, the role of
      macroautophagy in mature CNS neurons, and the relationship with human disease
      neuropathology, remains unclear. Here we describe mice deficient in an essential
      macroautophagy component, Atg7, specifically within postnatal CNS neurons.
      RESULTS: Postnatal forebrain-specific Atg7 conditional knockout (cKO) mice
      displayed age-dependent neurodegeneration and ubiquitin- and p62-positive
      inclusions. Phosphorylated tau was significantly accumulated in Atg7 cKO brains,
      but neurofibrillary tangles that typify end-stage human tauopathy were not
      apparent. A major tau kinase, glycogen synthase kinase 3beta (GSK3beta), was also
      accumulated in Atg7 cKO brains. Chronic pharmacological inhibition of tau
      phosphorylation, or genetic deletion of tau, significantly rescued Atg7
      deficiency-mediated neurodegeneration, but did not suppress inclusion formation.
      CONCLUSIONS: These data elucidate a role for macroautophagy in the long-term
      survival and physiological function of adult CNS neurons. Neurodegeneration in
      the context of macroautophagy deficiency is mediated through a phospho-tau
      pathway.

PMID- 22998732
TI  - Social skills and depressive symptoms across adolescence: social support as a
      mediator in girls versus boys.
AB  - The current population-based study of Norwegian adolescents examined gender
      specific patterns in the prospective association between social skills in early
      adolescence (age 12.5; n = 566) and changes in depressive symptoms from early to
      late adolescence (age 16.5; n = 375). Further, a potential mediation effect of
      social support (from peers, parents, and teachers) in middle adolescence (age
      14.5; n = 456) was examined. The findings indicated that low levels of social
      skills in early adolescence predicted increases in depressive symptoms for both
      girls and boys. Low levels of friend support in middle adolescence mediated this
      relationship for girls, but not boys. The findings underline the importance of
      including social skills training in primary programs designed to prevent
      development of depression. Preventive programs should also include actions on how
      girls can cope with interpersonal difficulties.

PMID- 22998733
TI  - Etanercept-induced injection site reactions: potential pathomechanisms and
      clinical assessment.
AB  - INTRODUCTION: Etanercept (ETN) is a tumor necrosis factor alpha (TNF-alpha)
      antagonist used for the treatment of chronic inflammatory disorders. Injection
      site reactions (ISRs) are reported to be the most common adverse event of ETN
      therapy. While their mechanisms are not completely understood, the occurrence of
      ETN-ISRs could indicate a risk of systemic immune-mediated severe adverse drug
      reactions. AREAS COVERED: Based on two cases and a review of the literature, the
      characteristics and frequency of ETN-ISRs were assessed. This article discusses
      their potential mechanisms and clinical relevance, and provides recommendations
      for the management of patients presenting with ETN-ISRs. EXPERT OPINION:
      Basically, irritative and immune-mediated ISRs may be distinguished. The
      formation of anti-drug antibodies (ADAs) may promote immune-mediated ISRs that
      likely represent either anaphylactic type I reactions, or cutaneous Arthus-like
      type III reactions according to the Coombs and Gell classification. A
      differentiation between these reactions by clinical course and etanercept-skin
      testing may help to decide if ETN treatment should be stopped to avoid the
      development of more severe adverse drug reactions if ISRs occur.

PMID- 22998734
TI  - Chemical modification of carbohydrates in tissue sections may unmask mucin
      antigens.
AB  - Expression of mucins in cells and tissues is of great diagnostic and prognostic
      importance, and immunohistochemistry frequently is used to detect them. Reports
      concerning mucin localization in sections sometimes are conflicting, however,
      partly because immunogenic regions of the mucin molecule may be masked and thus
      not available for binding to an antibody. We modified carbohydrates in tissue
      sections chemically to enhance the binding of monoclonal mucin antibodies and of
      the lectin, Vicia villosa B4, to human tissue. The immunohistochemical
      localization of MUC1 and the simple mucin-type antigens, Tn and sialyl-Tn, was
      influenced by oxidation with periodic acid and by beta-elimination before
      incubation. In some epithelial cells the staining was prevented by these
      procedures while in other cells it was evident. It appears that chemical
      modification can either destroy some antigen binding sites or unmask cryptic
      antigen binding sites in the mucin molecule and thereby make them accessible for
      immunohistochemical detection.

PMID- 22998735
TI  - The osteoclast, bone remodelling and treatment of metabolic bone disease.
AB  - BACKGROUND: Bone remodelling maintains skeletal integrity by osteoclasts removing
      foci of damaged bone and osteoblasts replacing them with new bone. Diseases
      associated with increased bone resorption have increased remodelling often with
      inadequate bone formation and increased risk of fracture. New therapies are
      needed for these diseases to reduce resorption and increase formation. DESIGN:
      The molecular mechanisms regulating osteoclast and osteoblast functions have
      become better understood in the past 20 years and have led to questioning of the
      long-held notion that osteoblastic cells have the dominant regulatory role over
      osteoclastic cells in bone remodelling. Here, we review current knowledge of how
      osteoclast formation and functions are regulated and describe how enhanced
      understanding of these has led to development of new drugs for the management of
      common bone diseases characterized by increased bone resorption. RESULTS:
      Osteoclast formation and functions are regulated by cytokines, especially
      receptor activator of NF-kappaB ligand (RANKL) and macrophage-colony-stimulating
      factor (M-CSF). The differentiation, activity and lifecycle of osteoclasts are
      regulated in part by other cells that reside within the bone. These include
      osteoblasts, osteocytes and immune cells, which express these cytokines in
      response to most factors that promote bone resorption. RANKL and M-CSF activate
      numerous signalling pathways, which are potential targets for therapeutic
      intervention. Importantly, osteoclastic cells also function as positive and
      negative regulators of osteoblastic bone formation. CONCLUSIONS: There are
      multiple targets within osteoclasts for pharmacologic intervention to prevent
      bone loss in osteoporosis and other resorptive bone diseases. However, novel
      therapies could also affect osteoblastic cell functions.

PMID- 22998736
TI  - A quantitative screening method to detect rater-introduced bias in clinical
      ratings.
AB  - BACKGROUND: We suggest a 'screening test' to examine large data files with
      clinical ratings for the occurrence of rater-introduced bias prior to using the
      data for quantitative analyses. The test is based on a statistical model in which
      a well-standardized interval-scale outcome (for example, milk yield) is related
      to clinical ratings (for example, body condition scores) obtained from multiple
      contexts (for example, dairy herds). FINDINGS: 84,968 calvings from 279 herds,
      with subsequent body condition scores performed by 117 veterinarians within the
      first 21 days postpartum were analyzed with a multilevel random coefficient
      regression model. The model included an independent variable, where body
      condition score was centered within veterinarian. This is a so-called comparison
      effect to describe possible rater-introduced bias in the body condition scores. A
      highly significant comparison effect was found for second and older parities,
      indicating occurrence of possible rater-introduced bias in this large multi-herd
      data file. CONCLUSIONS: A within-group centering technique (the comparison
      effect) appeared to be useful for discriminating between biased and unbiased
      clinical scores. In some cases, this test for bias should prevent further
      analysis of the data and divert the focus of study to the calibration of raters
      or alternative study designs.

PMID- 22998738
TI  - Utility of the point of care CD4 analyzer, PIMA, to enumerate CD4 counts in the
      field settings in India.
AB  - BACKGROUND: In resource limited settings non-availability of CD4 count facility
      at the site could adversely affect the ART roll out programme. Point of care CD4
      enumerating equipments can make the CD4 count available at the site of care and
      improve the patients' management considerably. This study is aimed at determining
      the utility of a Point of Care PIMA CD4 analyzer (Alere, Germany) in the field
      settings in India. METHOD: The blood samples were collected from 1790
      participants at 21 ART centers from different parts of the country and tested
      using PIMA and the reference methods (FACSCalibur, FACSCount and CyFlow SL3). The
      paired finger prick and venous blood samples from 175 participants were tested by
      the PIMA CD4 Analyzer and then by FACSCalibur. RESULT: The CD4 counts obtained by
      PIMA CD4 analyzer showed excellent correlation with the counts obtained by the
      reference methods; for venous blood the Pearson's r was 0.921, p < 0.001 and the
      relative bias was 0.2% (range: -42 to 42%) and for finger prick samples, the
      Pearson's r was 0.856 and the relative bias was -9.1% (range: -46% to 27%). For
      CD4 ranges; <250, 251-350, 351-500 and >500 cells/mm3, the differences in the
      median CD4 counts obtained by the reference method and the PIMA analyzer were not
      significant (P > 0.05) and the relative bias were low (-7 to 5.1%). The
      Intermachine comparison showed variation within the acceptable limit of%CV of
      10%. CONCLUSION: In the field settings, the POC PIMA CD4 analyzer gave CD4 counts
      comparable to the reference methods for all CD4 ranges. The POC equipment could
      identify the patients eligible for ART in 91% cases. Adequate training is
      necessary for finger prick sample collection for optimum results.
      Decentralization of CD4 testing by making the CD4 counts available at primary
      health centers, especially in remote areas with minimum or no infrastructure
      would reduce the missed visits and improve adherence of the patients.

PMID- 22998737
TI  - Effects of weight loss and insulin reduction on arterial stiffness in the SAVE
      trial.
AB  - BACKGROUND: Chronic arterial stiffness contributes to the negative health effects
      of obesity and insulin resistance, which include hypertension, stroke, and
      increased cardiovascular and all-cause mortality. Weight loss and improved
      insulin sensitivity are individually associated with improved central arterial
      stiffness; however, their combined effects on arterial stiffness are poorly
      understood. The purpose of this study was to determine how insulin levels modify
      the improvements in arterial stiffness seen with weight loss in overweight and
      obese young adults. METHODS: To assess the effects of weight loss and decreased
      fasting insulin on vascular stiffness, we studied 339 participants in the Slow
      the Adverse Effects of Vascular Aging (SAVE) trial. At study entry, the
      participants were aged 20-45, normotensive, non-diabetic, and had a body-mass
      index of 25-39.9 kg/m2. Measures of pulse wave velocity (PWV) in the central
      (carotid-femoral (cfPWV)), peripheral (femoral-ankle (faPWV)), and mixed
      (brachial-ankle (baPWV)) vascular beds were collected at baseline and 6 months.
      The effects of 6-month change in weight and insulin on measures of PWV were
      estimated using multivariate regression. RESULTS: After adjustment for baseline
      risk factors and change in systolic blood pressure, 6-month weight loss and 6
      month change in fasting insulin independently predicted improvement in baPWV but
      not faPWV or cfPWV. There was a significant interaction between 6-month weight
      change and change in fasting insulin when predicting changes in baPWV (p <
      0.001). Individuals experiencing both weight loss and insulin reductions showed
      the greatest improvement in baPWV. CONCLUSIONS: Young adults with excess weight
      who both lower their insulin levels and lose weight see the greatest improvement
      in vascular stiffness. This improvement in vascular stiffness with weight loss
      and insulin declines may occur throughout the vasculature and may not be limited
      to individual vascular beds.

PMID- 22998739
TI  - Improvement in onychomycosis after initiation of combined antiretroviral therapy.
AB  - BACKGROUND: Onychomycosis is frequent in patients with late and advanced HIV
      disease; immunocompromised patients may develop atypical clinical presentations
      that can be difficult to control. Current treatment for onychomycosis is based on
      the prolonged administration of antifungal therapies that may have significant
      interactions with combined antiretroviral therapy (cART). An improvement in
      certain HIV-associated opportunistic infections has been associated with
      initiation of cART. OBJECTIVES: The aim of this study was to analyze the
      influence of cART on the outcome of onychomycosis in HIV-infected patients.
      METHODS: HIV-infected patients with dermatologic lesions attending the National
      Institute of Respiratory Diseases were asked to undergo physical examination.
      Detailed clinical histories were recorded. Routine laboratory tests, CD4 T cell
      count, and HIV viral load were performed. Onychomycosis was diagnosed on the
      basis of clinical appearance. Nail scrapings were collected from toenails and
      fingernails. Specimens were analyzed using direct microscopy. Nail changes after
      cART initiation were assessed by clinical examination. RESULTS: Improvement in
      onychomycosis was observed in six patients with late and advanced HIV disease
      after initiation of cART. Complete resolution of onychomycosis was observed in
      one patient without the use of antifungal therapy; one patient required topical
      antifungal treatment, and two patients required systemic antifungal treatment to
      achieve complete resolution. CONCLUSIONS: Onychomycosis should be included in the
      group of pathologies that improve with cART-induced immune reconstitution. The
      pathogenesis of onychomycosis in HIV disease warrants investigation in the
      context of cell-mediated immunity restoration.

PMID- 22998741
TI  - Effect of partial NaCl substitution with KCl on the texture profile,
      microstructure, and sensory properties of low-moisture mozzarella cheese.
AB  - The effect of partial substitution of NaCl with KCl on texture profile, soluble
      Ca, K, Na, and P, and microstructure of low-moisture mozzarella cheese (LMMC) was
      investigated. LMMC batches were prepared using four combinations of NaCl and KCl
      salt viz., NaCl only, NaCl:KCl, 3:1, 1:1 and 1:3 (w/w); all used at of 46 g/kg
      curd and plasticised in 4% brine containing the above salt mixtures. Texture
      profile, microstructure, and percentages of soluble Ca, K, Na, and P were
      determined. There were no significant differences in hardness, cohesiveness,
      adhesiveness, and gumminess among the experimental LMMC batches. Environmental
      scanning electron microscopy images showed compact and homogeneous structure of
      LMMC at day 27 of storage; however, no significant difference was observed among
      the experimental LMMC batches. Hardness increased significantly in all
      experimental LMMC during storage. LMMC salted with NaCl/KCl mixtures had almost
      similar sensory properties compared with the control. There was no significant
      difference in creaminess, bitterness, saltiness, sour-acid, and vinegary taste
      among the experimental LMMC at the same storage period.

PMID- 22998740
TI  - Motivation and social capital among prospective blood donors in three large blood
      centers in Brazil.
AB  - BACKGROUND: Studies analyzing motivation factors that lead to blood donation have
      found altruism to be the primary motivation factor; however, social capital has
      not been analyzed in this context. Our study examines the association between
      motivation factors (altruism, self-interest, and response to direct appeal) and
      social capital (cognitive and structural) across three large blood centers in
      Brazil. STUDY DESIGN AND METHODS: We conducted a cross-sectional survey of 7635
      donor candidates from October 15 through November 20, 2009. Participants
      completed self-administered questionnaires on demographics, previous blood
      donation, human immunodeficiency virus testing and knowledge, social capital, and
      donor motivations. Enrollment was determined before the donor screening process.
      RESULTS: Among participants, 43.5 and 41.7% expressed high levels of altruism and
      response to direct appeal, respectively, while only 26.9% expressed high levels
      of self-interest. More high self-interest was observed at Hemope-Recife (41.7%).
      Of participants, 37.4% expressed high levels of cognitive social capital while
      19.2% expressed high levels of structural social capital. More high cognitive and
      structural social capital was observed at Hemope-Recife (47.3 and 21.3%,
      respectively). High cognitive social capital was associated with high levels of
      altruism, self-interest, and response to direct appeal. Philanthropic and high
      social altruism were associated with high levels of altruism and response to
      direct appeal. CONCLUSION: Cognitive and structural social capital and social
      altruism are associated with altruism and response to direct appeal, while only
      cognitive social capital is associated with self-interest. Designing marketing
      campaigns with these aspects in mind may help blood banks attract potential blood
      donors more efficiently.

PMID- 22998742
TI  - An exploratory study of combination buspirone and melatonin SR in major
      depressive disorder (MDD): a possible role for neurogenesis in drug discovery.
AB  - We used in vitro neurogenesis-based human neural stem cell (hNSCs) assays and
      rodent in vivo behavioral assays to identify potential novel antidepressants. A
      combination of buspirone and melatonin displayed antidepressant activity in these
      assays whereas neither buspirone nor melatonin alone showed any antidepressant
      like profile. After evaluating numerous combination ratios, we determined that
      low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal
      antidepressant efficacy in our pre-clinical platform. The low dose of buspirone
      suggested that antidepressant efficacy might be achieved with only minimal
      adverse event liability. Based on these data, we conducted an exploratory 6-week,
      multi-center, double-blind, randomized, placebo- and comparator-controlled study
      of the combination of buspirone and melatonin in subjects with acute Major
      Depressive Disorder (MDD). The combination treatment revealed a significant
      antidepressant response in subjects with MDD on several measures (Clinical Global
      Impression of Severity and Improvement, Inventory of Depressive Symptomatology)
      compared to either placebo or buspirone 15 mg monotherapy. These preliminary
      findings have clinical implications and suggest that a platform of pre-clinical
      neurogenesis matched with confirmatory behavioral assays may be useful as a drug
      discovery strategy.

PMID- 22998743
TI  - Evaluation of behavioral and neurochemical changes induced by ketamine in rats:
      implications as an animal model of mania.
AB  - Bipolar disorder (BD) is a chronic, prevalent, and highly debilitating
      psychiatric illness characterized by recurrent manic and depressive episodes.
      Mood stabilizing agents such as lithium and valproate are two primary drugs used
      to treat BD. To develop a novel animal model of mania (hallmark of BD), it is
      important to assess the therapeutic and prophylactic effect of these mood
      stabilizers on the new candidate target animal model. The present work
      investigates the therapeutic and prophylactic value of lithium and valproate in a
      novel preclinical animal model of mania, induced by ketamine. In the prevention
      protocol, wistar rats were pretreated with lithium (47.5 mg/kg, i.p., twice a
      day), valproate (200 mg/kg, i.p., twice a day), or saline (i.p., twice a day) for
      14 days. Between days 8 and 14, the rats were treated with ketamine (25 mg/kg,
      i.p.) or saline. In the reversal protocol, rats first received ketamine (25
      mg/kg, i.p.) or saline. After, the administration of lithium, valproate, or
      saline was carried out for seven days. Our results indicated that lithium and
      valproate reversed and prevented ketamine-induced hyperlocomotion. Moreover,
      lithium and valproate reversed (prefrontal cortex, hippocampus, and striatum) and
      prevented (prefrontal cortex, hippocampus, striatum, and amygdala) the increase
      of the TBARS level induced by ketamine. The protein carbonyl formation, induced
      by ketamine, was reversed by lithium and valproate in the prefrontal cortex,
      hippocampus, and striatum, and prevented only in the amygdala. These findings
      support the notion that the administration of ketamine might be a promising
      pharmacological animal model of mania, which could play a role in the
      pathophysiology of BD.

PMID- 22998744
TI  - Quantitative nanoscale imaging of lattice distortions in epitaxial semiconductor
      heterostructures using nanofocused X-ray Bragg projection ptychography.
AB  - We imaged nanoscale lattice strain in a multilayer semiconductor device prototype
      with a new X-ray technique, nanofocused Bragg projection ptychography. Applying
      this technique to the epitaxial stressor layer of a SiGe-on-SOI structure, we
      measured the internal lattice behavior in a targeted region of a single device
      and demonstrated that its internal strain profile consisted of two competing
      lattice distortions. These results provide the strongest nondestructive test to
      date of continuum modeling predictions of nanoscale strain distributions.

PMID- 22998745
TI  - Infectious complications following allogeneic stem cell transplantation: reduced
      intensity vs. myeloablative conditioning regimens.
AB  - BACKGROUND: In allogeneic stem cell transplantation (allo-SCT), reduced-intensity
      conditioning (RIC) is known for producing less regimen-related toxicity. However,
      whether or not RIC reduces the risk for infection and infection-related mortality
      (IRM) remains controversial. METHODS: We retrospectively analyzed infectious
      episodes and IRMs after allo-SCTs by time period and by the intensity of the
      conditioning regimen (RIC [n = 81] vs. myeloablative conditioning, MAC [n =
      150]). RESULTS: The cumulative incidence of any kind of infection was lower in
      the RIC group through the entire period (72% vs. 87%; P = 0.007). The onset of
      infections was deferred in the RIC group as compared with the MAC group (P =
      0.012). Bacteremia occurred less frequently in the RIC group through the entire
      period (5% vs. 14%; P = 0.044). However, the incidences of cytomegalovirus
      reactivation and disease, herpes zoster, virus-associated hemorrhagic cystitis,
      and invasive fungal infection were not different between the two groups.
      Furthermore, there was no difference in relapse-free survival and IRM between the
      two conditioning regimens. CONCLUSION: Careful monitoring and appropriate
      preventive/therapeutic strategies for infectious complications, comparable to
      those for allo-SCT recipients with MAC, should also be applied to those with RIC,
      especially after engraftment.

PMID- 22998746
TI  - Two-year follow-up of a randomized trial of spectacles plus alternate-day
      patching to treat strabismic amblyopia.
AB  - PURPOSE:   To compare spectacles plus alternate-day patching for 8 hr or more
      with spectacles plus patching for 8 hr or more 6 days weekly to treat strabismic
      amblyopia 1 year after a 1-year randomized trial. METHODS: Forty children (mean
      age, 4.3 years) participated. Refractive correction was provided. The children
      were assigned to alternate-day patching for 8 hr or more or patching for 8 hr or
      more daily 6 days weekly. VA, binocular function, and refractive errors were
      measured after 2 years. The main outcome measure was the median VA change in the
      amblyopic eye after 2 years. RESULTS: The median VA change in the amblyopic eye
      at the 2-year visit was significantly (p = 0.0453) greater with alternate-day
      patching (0.8 log unit) versus patching daily 6 days weekly (0.6 log unit). The
      final median VA in the amblyopic eyes was 0.0 logMAR in the alternate-day
      patching group and 0.1 logMAR in the daily patching group. Binocular function
      improved with both treatments. The median spherical equivalent (SE) refractive
      error increased in the fellow eyes (alternate-day patching, p < 0.0001; patching
      daily 6 days weekly, p = 0.0033); no change was found in the amblyopic eyes in
      either group. CONCLUSIONS: The magnitude of the VA change 2 years after treatment
      with spectacles plus alternate-day patching for 8 hr or more was significantly
      greater than with spectacles plus daily patching for 8 hr or more 6 days weekly
      for strabismic amblyopia. However, the final median VA did not differ
      significantly between the two treatments.

PMID- 22998747
TI  - A small RNA derived from RNA coactivator SRA blocks steroid receptor signaling
      via inhibition of Pus1p-mediated pseudouridylation of SRA: evidence of a novel
      RNA binding domain in the N-terminus of steroid receptors.
AB  - Estrogen receptors (ERs) and androgen receptors (ARs) are important targets for
      cancer therapy; however, the efficacy of receptor antagonists is limited, and
      alternative strategies are needed. Steroid receptor RNA Activator (SRA) is a
      long, noncoding RNA coactivator (although some protein-encoding 5' splice
      variants have also been reported) that requires pseudouridylation by Pus1p to
      stimulate steroid receptor signaling. A uridine at position 206 (U206), which is
      located in small hairpin structure STR5 in the conserved SRA core sequence, is a
      critical target for pseudouridylation. We assessed if synthetic STR5 could serve
      as a novel competitive inhibitor of ERalpha and AR signaling by disrupting the
      Pus1p-SRA-steroid receptor axis. STR5 specifically inhibited Pus1p-dependent
      pseudouridylation of SRA with higher efficiency than STR5 mutant U206A. We show
      that SRA binds to the N-terminal domain (NTD) of ERalpha and AR with high
      affinity despite the absence of a recognizable RNA binding motif (RBM). Finally,
      we show that STR5 specifically inhibits ERalpha- and AR-dependent transactivation
      of target genes in steroid-sensitive cancer cells, consistent with disruption of
      the targeted Pus1p-SRA pathway. Together, our results show that the NTD of
      ERalpha and AR contains a novel RBM that directly binds SRA, and that STR5 can
      serve as a novel class of RNA inhibitor of ERalpha and AR signaling by
      interfering with Pus1p-mediated SRA pseudouridylation. Targeting this unexplored
      receptor signaling pathway may pave the way for the development of new types of
      cancer therapeutics.

PMID- 22998748
TI  - Health policymakers' knowledge and opinions of physicians smoking and tobacco
      policy control in Lao PDR.
AB  - BACKGROUND: In 2007, a regulation on smoke-free health facilities and
      institutions was adopted by the Lao government. Little is known about health
      policymakers' knowledge and opinions regarding tobacco policy control, including
      physicians' behaviour. This paper aims to describe the knowledge of Lao health
      policymakers and their opinions regarding physicians tobacco use and national
      smoking policy control. METHODS: In 2007, we made a qualitative explorative study
      with data from a purposive sample of 18 key informants through semi-structured,
      face-to-face interviews. The key informants, who were heads of departments,
      directors of hospitals and directors of centres, mainly worked at the national
      level, and some provincial levels. Content analysis was used. RESULTS:
      Policymakers perceived the inadequate implementation of a smoke-free regulation
      and policy as being a barrier and that the general public may not accept
      physicians smoking, since they are regarded as role models. Most of the
      respondents mentioned that regulations or laws related to control of smoking in
      health institutions are available in Laos, but they lacked detailed knowledge of
      them probably because regulations as well as the smoke-free policy documents were
      not widely disseminated. The respondents agreed that anti-smoking education
      should be integrated in the training curricula, especially in the medical
      schools, and that the provision of counselling on health consequences from
      smoking and methods of smoking cessation was important. CONCLUSION: This study
      contributes to tobacco policy evidence and to knowledge regarding factors related
      to the uptake of evidence into policymaking. Dissemination and implementation of
      a tobacco control policy nationally, and integration of tobacco cessation
      training programs in the curricula were found to be productive approaches for
      improvement.

PMID- 22998749
TI  - 'Representative Genes', is it OK to use a small amount of data to obtain a
      phylogeny that is at least close to the true tree?
AB  - Despite the problems associated with the one-gene-constructed phylogenetic
      relationships, recently it has been shown that merely adding more sequences to
      the analyses is not enough to resolve all the inconsistencies present in these
      relationships. In this work, the existence of 'representative' genes for groups
      of species is evaluated in terms of efficiency (costs/benefits), employing the
      cytochrome c oxidase subunit I (COI) and the penguins' phylogeny as a case study.
      'Representative' genes are very useful and they could produce good results for
      first approaches or humble laboratories, especially if the gene is chosen
      depending on the time scale and objectives of our work.

PMID- 22998750
TI  - Does the small tyrosine kinase inhibitor Imatinib mesylate counteract diabetes by
      affecting pancreatic islet amyloidosis and fibrosis?
AB  - INTRODUCTION: The small tyrosine kinase inhibitor Imatinib Mesylate (Gleevec)
      protects against diabetes, but it is not known how. AREAS COVERED: It has been
      suggested that islet amyloid and fibrotic deposits promote beta-cell failure and
      death, leading to Type-2 diabetes. As Imatinib is known to possess anti
      fibrotic/amyloid properties, in for example systemic sclerosis and mouse models
      for Alzheimer's disease, the present review will discuss the possibility that
      Imatinib acts, at least in part, by ameliorating islet hyalinization and its
      consequences in the pathogenesis of Type-2 diabetes. EXPERT OPINION: A better
      understanding of how Imatinib counteracts Type-2 diabetes will possibly help to
      clarify the pathogenic role of islet amyloid and fibrosis, and hopefully lead to
      improved treatment of the disease.

PMID- 22998751
TI  - Epidural electrical stimulation for the treatment of chronic poststroke aphasia:
      still compulsory 6 years later!
AB  - Implanted cortical stimulation is foreseen to facilitate functional poststroke
      recovery. Until now, no study has concluded on its pathophysiological mechanism.
      We report a case of a 58-year-old patient for whom cortical stimulation triggered
      a drastic enhancement of speech performances. The effects remain reversible after
      6 years of stimulation, reflecting intra/inter-hemispheric modulation.

PMID- 22998752
TI  - Exercise and chronic fatigue syndrome: maximize function, minimize post
      exertional malaise.

PMID- 22998753
TI  - Antimicrobial susceptibility of porcine Brachyspira hyodysenteriae and
      Brachyspira pilosicoli isolated in Sweden between 1990 and 2010.
AB  - BACKGROUND: The anaerobic spirochetes Brachyspira hyodysenteriae and Brachyspira
      pilosicoli cause diarrheal diseases in pigs. Their fastidious nature has hampered
      standardization of methods for antimicrobial susceptibility testing. For
      monitoring of antimicrobial susceptibility wild type cutoff values are needed to
      define where the wild type distribution of MICs ends and no approved cutoffs are
      available for Brachyspira spp. In this study antimicrobial susceptibility data
      for both species (in total 906 isolates) were compiled and analyzed and wild type
      cut off values for B. hyodysenteriae proposed. METHODS: The MICs of tiamulin,
      valnemulin, tylosin, tylvalosin, doxycycline and lincomycin were determined by
      broth dilution in brain heart infusion broth supplemented with 10% fetal calf
      serum. RESULTS: The compiled MICs from the broth dilution tests of the B.
      hyodysenteriae type strain, B78T (ATCC(r) 27164T), showed that the method yields
      reproducible results. In an international perspective the frequencies of isolates
      with decreased antimicrobial susceptibility were low among both B. hyodysenteriae
      and B. pilosicoli. However, in B. pilosicoli a constant level of 10-15% isolates
      with tiamulin MICs >4 MUg/ml was detected between 2002 and 2010 and in B.
      hyodysenteriae a gradual increase in tiamulin MICs was seen between 1990 and 2003
      although this increase has ceased during the last years. The wild type cutoff
      values proposed for B. hyodysenteriae are: tiamulin >0.25 MUg/ml, valnemulin
      >0.125 MUg/ml, tylosin >16 MUg/ml, tylvalosin >1 MUg/ml, lincomycin >1 MUg/ml and
      doxycycline >0.5 MUg/ml. CONCLUSIONS: The broth dilution method used in this
      study has over the years generated tightly grouped MIC populations for the field
      isolates and reproducible results for the control strain B78T and is therefore a
      suitable antimicrobial susceptibility test method for monitoring of Brachyspira
      spp. Here we propose wild type cutoff values for six antimicrobial agents for B.
      hyodysenteriae tested by broth dilution based on MIC distributions and the
      current knowledge on mechanisms of resistance in this species. There are few
      studies on antimicrobial resistance mechanisms and MIC distributions in B.
      pilosicoli but to some extent the cutoff values proposed for B. hyodysenteriae
      may be applicable also for monitoring of antimicrobial susceptibility in B.
      pilosicoli.

PMID- 22998754
TI  - A 12-week double-blind randomized clinical trial of vitamin D3 supplementation on
      body fat mass in healthy overweight and obese women.
AB  - BACKGROUND: Vitamin D concentrations are linked to body composition indices,
      particularly body fat mass. Relationships between hypovitaminosis D and obesity,
      described by both BMI and waist circumference, have been mentioned. We have
      investigated the effect of a 12-week vitamin D3 supplementation on anthropometric
      indices in healthy overweight and obese women. METHODS: In a double-blind,
      randomized, placebo-controlled, parallel-group trial, seventy-seven participants
      (age 38 +/- 8.1 years, BMI 29.8 +/- 4.1 kg/m2) were randomly allocated into two
      groups: vitamin D (25 MUg per day as cholecalciferol) and placebo (25 MUg per day
      as lactose) for 12 weeks. Body weight, height, waist, hip, fat mass, 25(OH) D,
      iPTH, and dietary intakes were measured before and after the intervention.
      RESULTS: Serum 25(OH)D significantly increased in the vitamin D group compared to
      the placebo group (38.2 +/- 32.7 nmol/L vs. 4.6 +/- 14.8 nmol/L; P<0.001) and
      serum iPTH concentrations were decreased by vitamin D3 supplementation (-0.26 +/-
      0.57 pmol/L vs. 0.27 +/- 0.56 pmol/L; P<0.001). Supplementation with vitamin D3
      caused a statistically significant decrease in body fat mass in the vitamin D
      group compared to the placebo group (-2.7 +/- 2.1 kg vs. -0.47 +/- 2.1 kg;
      P<0.001). However, body weight and waist circumference did not change
      significantly in both groups. A significant reverse correlation between changes
      in serum 25(OH) D concentrations and body fat mass was observed (r = -0.319, P =
      0.005). CONCLUSION: Among healthy overweight and obese women, increasing 25(OH) D
      concentrations by vitamin D3 supplementation led to body fat mass reduction.

PMID- 22998756
TI  - Clinical regression of squamous cell carcinoma and keratoacanthomas in a patient
      treated with a hypomethylating agent.

PMID- 22998755
TI  - Complete genome sequence of an astrovirus identified in a domestic rabbit
      (Oryctolagus cuniculus) with gastroenteritis.
AB  - A colony of domestic rabbits in Tennessee, USA, experienced a high-mortality
      (~90%) outbreak of enterocolitis. The clinical characteristics were one to six
      days of lethargy, bloating, and diarrhea, followed by death. Heavy intestinal
      coccidial load was a consistent finding as was mucoid enteropathy with cecal
      impaction. Preliminary analysis by electron microscopy revealed the presence of
      virus-like particles in the stool of one of the affected rabbits. Analysis using
      the Virochip, a viral detection microarray, suggested the presence of an
      astrovirus, and follow-up PCR and sequence determination revealed a previously
      uncharacterized member of that family. Metagenomic sequencing enabled the
      recovery of the complete viral genome, which contains the characteristic
      attributes of astrovirus genomes. Attempts to propagate the virus in tissue
      culture have yet to succeed. Although astroviruses cause gastroenteric disease in
      other mammals, the pathogenicity of this virus and the relationship to this
      outbreak remains to be determined. This study therefore defines a viral species
      and a potential rabbit pathogen.

PMID- 22998757
TI  - Hospital-based shootings in the United States: 2000 to 2011.
AB  - STUDY OBJECTIVE: Workplace violence in health care settings is a frequent
      occurrence. Emergency departments (EDs) are considered particularly vulnerable.
      Gunfire in hospitals is of particular concern; however, information about such
      workplace violence is limited. Therefore, we characterize US hospital-based
      shootings from 2000 to 2011. METHODS: Using LexisNexis, Google, Netscape, PubMed,
      and ScienceDirect, we searched reports for acute care hospital shooting events in
      the United States for 2000 through 2011. All hospital-based shootings with at
      least 1 injured victim were analyzed. RESULTS: Of 9,360 search "hits," 154
      hospital-related shootings were identified, 91 (59%) inside the hospital and 63
      (41%) outside on hospital grounds. Shootings occurred in 40 states, with 235
      injured or dead victims. Perpetrators were overwhelmingly men (91%) but
      represented all adult age groups. The ED environs were the most common site
      (29%), followed by the parking lot (23%) and patient rooms (19%). Most events
      involved a determined shooter with a strong motive as defined by grudge (27%),
      suicide (21%), "euthanizing" an ill relative (14%), and prisoner escape (11%).
      Ambient society violence (9%) and mentally unstable patients (4%) were
      comparatively infrequent. The most common victim was the perpetrator (45%).
      Hospital employees composed 20% of victims; physician (3%) and nurse (5%) victims
      were relatively infrequent. Event characteristics that distinguished the ED from
      other sites included younger perpetrator, more likely in custody, and unlikely to
      have a personal relationship with the victim (ill relative, grudge, coworker). In
      23% of shootings within the ED, the weapon was a security officer's gun taken by
      the perpetrator. Case fatality inside the hospital was much lower in the ED
      setting (19%) than other sites (73%). CONCLUSION: Although it is likely that not
      every hospital-based shooting was identified, such events are relatively rare
      compared with other forms of workplace violence. The unpredictable nature of this
      type of event represents a significant challenge to hospital security and
      effective deterrence practices because most perpetrators proved determined and a
      significant number of shootings occur outside the hospital building.

PMID- 22998758
TI  - Effect of milk composition and coagulation traits on Grana Padano cheese yield
      under field conditions.
AB  - The aim of this study was to assess the effect of chemical composition,
      coagulation properties, pH, and titratable acidity (TA, SH degrees /50 ml) of vat
      milk on Grana Padano cheese yield (CY) under field conditions. Twelve cheese
      making sessions were carried out from February to December 2009 in a dairy
      cooperative of Grana Padano Consortium (Italy), for a total of 96 vats of milk
      processed. For each vat, samples of raw milk were collected and analysed for
      quality traits (fat, protein, and casein contents), pH, TA, and milk coagulation
      properties (MCP), measured as rennet coagulation time (RCT, min), curd-firming
      time (k(20), min), and curd firmness (a(30), mm). Cheese yield was expressed as
      kilograms of cheese per 100 kg milk transformed, and was measured after 2 d of
      drainage. Fat, protein, and casein contents were positively and strongly
      correlated with CY (coefficients of correlation, r = 0.72, 0.88, and 0.84,
      respectively; P < 0.001). Coagulation properties were moderately and
      significantly (P < 0.001) related to CY: milk that coagulated earlier and had
      stronger a(30) was associated to greater CY. Cheese yield was analysed with a
      model that accounted for fixed effects of cheese-making day, fat and protein
      content, TA, and a(30). Significance was found for all the effects (P < 0.05).
      Milk characterised by high values of a(30) resulted in higher CY than milk with
      low values of a 30, indicating that MCP could be used as indicators of cheese
      making efficiency. Future research should investigate the relationships between
      MCP and quality of cheese, and explore the feasibility of including MCP in
      multiple component milk pricing system for Grana Padano cheese production.

PMID- 22998759
TI  - Perceived deterrents to being a plasmapheresis donor in a voluntary,
      nonremunerated environment.
AB  - BACKGROUND: As demand for plasma-derived products increases internationally,
      maintaining a committed plasmapheresis panel membership is critical for blood
      collection agencies. This study addresses the current lack of knowledge regarding
      deterrents to the recruitment and retention of plasmapheresis donors in a
      voluntary nonremunerated environment. STUDY DESIGN AND METHODS: Nine focus groups
      (n = 84) and six individual interviews were conducted using semistructured
      schedules. Three focus groups were conducted with each category of eligible whole
      blood (WB) donors: those who had 1) declined to convert to plasmapheresis (DTC),
      2) converted but lapsed to WB (LWB), and 3) converted and lapsed from the panel
      completely (LFP). Transcript analysis revealed distinct deterrent categories.
      RESULTS: The time required for plasmapheresis was a universally identified
      deterrent, with concerns of donation frequency expectations shared between DTC
      and LWB. LWB and LFP both reported excessive questioning and paperwork, and
      eligibility requirements as deterrents. Unique deterrents for DTC were a lack of
      accurate knowledge about safety and process. LWB reported concerns about
      plasmapheresis donation outcomes; however, they were more committed to continuing
      donation than LFP, who reported donation not being salient, being too busy, and
      poorer donation experiences. CONCLUSION: Providing information to address safety
      and health concerns should be the focus for successful conversion to
      plasmapheresis. Setting donation frequency expectations at levels to which donors
      are accustomed may improve evaluations of the cost/benefit ratio of conversion
      and retention. Involvement levels (i.e., importance, personal meaning of
      donation) may be the key differentiator between those donors who return to WB and
      those that lapse altogether.

PMID- 22998760
TI  - Dual action antimicrobials: nitric oxide release from quaternary ammonium
      functionalized silica nanoparticles.
AB  - The synthesis of quaternary ammonium (QA)-functionalized silica nanoparticles
      with and without nitric oxide (NO) release capabilities is described.
      Glycidyltrialkylammonium chlorides of varied alkyl chain lengths (i.e., methyl,
      butyl, octyl, and dodecyl) were tethered to the surface of amine-containing
      silica nanoparticles via a ring-opening reaction. Secondary amines throughout the
      particle were then functionalized with N-diazeniumdiolate NO donors to yield dual
      functional nanomaterials with surface QAs and total NO payloads of 0.3 MUmol/mg.
      The bactericidal activities of singly (i.e., only NO-releasing or only QA
      functionalized) and dual (i.e., NO-releasing and QA-functionalized) functional
      nanoparticles were tested against Gram-positive  Staphylococcus aureus  and Gram
      negative  Pseudomonas aeruginosa . Particles with only NO release capabilities
      alone were found to be more effective against  P. aeruginosa , while particles
      with only QA-functionalities exhibited greater toxicity toward  S. aureus . The
      minimum bactericidal concentrations (MBC) of QA-functionalized particles
      decreased with increasing alkyl chain length against both microbes tested.
      Combining NO release and QA-functionalities on the same particle resulted in an
      increase in bactericidal efficacy against  S. aureus ; however, no change in
      activity against  P. aeruginosa  was observed compared to NO-releasing particles
      alone.

PMID- 22998761
TI  - Pulsed-laser desorption/ionization of clusters from biofunctional gold
      nanoparticles: implications for protein detections.
AB  - In this paper, we describe a pulsed-laser desorption/ionization mass spectrometry
      (LDI-MS) approach for the detection of proteins with femtomolar sensitivity
      through the analysis of gold (Au) clusters desorbed from aptamer-modified gold
      nanoparticles (Apt-AuNPs) on a nitrocellulose membrane (NCM). After the target
      protein (thrombin) was selectively captured by the surface-bound 29-mer thrombin
      binding aptamer (TBA(29)), the thrombin/TBA(29)-AuNP complexes were concentrated
      and deposited onto the NCM to form a highly efficient background-free surface
      assisted LDI substrate. Under pulsed laser irradiation (355 nm), the binding of
      thrombin decreased the desorption and/or ionization efficiencies of the Au atoms
      from the AuNP surfaces. The resulting decreases in the intensities of the signals
      for Au clusters in the mass spectra provided a highly amplified target-labeling
      indicator for the targeted protein. Under optimized conditions, this probe was
      highly sensitive (limit of detection: ca. 50 fM) and selective (by at least 1000
      fold over other proteins) toward thrombin; it also improved reproducibility (<5%)
      of ion production by presenting a more-homogeneous substrate surface, thereby
      enabling LDI-based measurements for the accurate and precise quantification of
      thrombin in human serum. This novel LDI-MS approach allows high-speed analyses of
      low-abundance thrombin with ultrahigh sensitivity; decorating the AuNP surfaces
      with other aptamers also allowed amplification of other biological signals.

PMID- 22998763
TI  - Influenza A H1N1/2009 infection in pediatric solid organ transplant recipients.
AB  - AIM AND METHOD: The aim of this study was to describe the clinical
      characteristics and outcome of pandemic influenza A H1N1/2009 (pH1N1) infection,
      in a retrospective cohort of pediatric patients with kidney and/or liver
      transplant and confirmed pH1N1 infection from June to December 2009, diagnosed in
      2 Spanish teaching hospitals. RESULTS: Forty-nine patients were included.
      Pneumonia was diagnosed in 4 patients (8.2%), and 3 of them required respiratory
      support. There were no related deaths. CONCLUSION: Antiviral treatment within 48
      h was associated with a lower likelihood of pneumonia (0/38, 0%) than treatment
      started after 48 h (4/11, 36.3%) (P < 0.01).

PMID- 22998762
TI  - Correlates of delayed sexual intercourse and condom use among adolescents in
      Uganda: a cross-sectional study.
AB  - BACKGROUND: Comprehensive sex education, including the promotion of consistent
      condom use, is still an important intervention strategy in tackling unplanned
      pregnancies, HIV/AIDS and sexually transmitted infections (STIs) among Ugandan
      adolescents. This study examines predictors of the intention to use a condom and
      the intention to delay sexual intercourse among secondary school students (aged
      12-20) in Uganda. METHODS: A school-based sample was drawn from 48 secondary
      schools throughout Uganda. Participants (N = 1978) completed a survey in English
      measuring beliefs regarding pregnancy, STIs and HIV and AIDS, attitudes, social
      norms and self-efficacy towards condom use and abstinence/delay, intention to use
      a condom and intention to delay sexual intercourse. As secondary sexual
      abstinence is one of the recommended ways for preventing HIV, STIs and unplanned
      pregnancies among the sexually experienced, participants with and without
      previous sexual experience were compared. RESULTS: For adolescents without sexual
      experience (virgins), self-efficacy, perceived social norms and attitude towards
      condom use predicted the intention to use condoms. Among those with sexual
      experience (non-virgins), only perceived social norm was a significant predictor.
      The intention to delay sexual intercourse was, however, predicted similarly for
      both groups, with attitudes, perceived social norm and self-efficacy being
      significant predictors. CONCLUSIONS: This study has established relevant
      predictors of intentions of safe sex among young Ugandans and has shown that the
      intention to use condoms is motivated by different factors depending on previous
      sexual experience. A segmented approach to intervention development and
      implementation is thus recommended.

PMID- 22998764
TI  - Chronic migraine: a therapeutic challenge for clinicians.
AB  - Chronic migraine is a common disabling condition. Severe migraine attacks should
      be treated with triptans, but these agents are contraindicated in patients with
      vascular problems and may not be effective or tolerated in around one third of
      the patients. New acute migraine therapies without vasoconstrictive activity and
      triptan-specific side effects are emerging. For the prophylaxis of chronic
      migraine, only topiramate and OnabotulinumtoxinA have been shown to be effective
      in placebo-controlled randomized trials, so novel therapeutic strategies are
      needed. The growing understanding of the pathophysiology of chronic migraine will
      contribute to the identification of new treatment targets.

PMID- 22998766
TI  - Acoustic system for the estimation of the temporary blood chamber volume of the
      POLVAD heart supporting prosthesis.
AB  - BACKGROUND: The paper presents a newly researched acoustic system for blood
      volume measurements for the developed family of Polish ventricular assist
      devices. The pneumatic heart-supporting devices are still the preferred solution
      in some cases, and monitoring of their operation, especially the temporary blood
      volume, is yet to be solved. METHODS: The prototype of the POLVAD-EXT prosthesis
      developed by the Foundation of Cardiac Surgery Development, Zabrze, Poland, is
      equipped with the newly researched acoustic blood volume measurement system based
      on the principle of Helmholtz's acoustic resonance. The results of static volume
      measurements acquired using the acoustic sensor were verified by measuring the
      volume of the liquid filling the prosthesis. Dynamic measurements were conducted
      on the hybrid model of the human cardiovascular system at the Foundation, with
      the Transonic T410 (11PLX transducer - 5% uncertainty) ultrasound flow rate
      sensor, used as the reference. RESULTS: The statistical analysis of a series of
      static tests have proved that the sensor solution provides blood volume
      measurement results with uncertainties (understood as a standard mean deviation)
      of less than 10%. Dynamic tests show a high correlation between the results of
      the acoustic system and those obtained by flow rate measurements using an
      ultrasound transit time type sensor. CONCLUSIONS: The results show that
      noninvasive, online temporary blood volume measurements in the POLVAD-EXT
      prosthesis, making use of the newly developed acoustic system, provides accurate
      static and dynamic measurements results. Conducted research provides the
      preliminary view on the possibility of reducing the additional sensor chamber
      volume in future.

PMID- 22998765
TI  - Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular
      administration in growing pigs.
AB  - BACKGROUND: Ketoprofen is a non-steroidal anti-inflammatory drug which has been
      widely used for domestic animals. Orally administered racemic ketoprofen has been
      reported to be absorbed well in pigs, and bioavailability was almost complete.
      The objectives of this study were to analyze R- and S-ketoprofen concentrations
      in plasma after oral (PO) and intra muscular (IM) routes of administration, and
      to assess the relative bioavailability of racemic ketoprofen for both enantiomers
      between those routes of administration in growing pigs. METHODS: Eleven pigs
      received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a
      randomized, crossover design with a 6-day washout period. Enantiomers were
      separated on a chiral column and their concentrations were determined by liquid
      chromatography-tandem mass spectrometry. Pharmacokinetic parameters were
      calculated and relative bioavailability (Frel) was determined for S and R 
      ketoprofen. RESULTS: S-ketoprofen was the predominant enantiomer in pig plasma
      after administration of the racemic mixture via both routes. The mean (+/- SD)
      maximum S-ketoprofen concentration in plasma (7.42 mg/L +/- 2.35 in PO and 7.32
      mg/L +/- 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55
      mg/L +/- 0.99 in PO and 3.23 mg/L +/- 0.70 in IM), and the terminal half-life was
      three times longer for S-ketoprofen (3.40 h +/- 0.91 in PO and 2.89 h +/- 0.85 in
      IM) than R-ketoprofen (1.1 h +/- 0.90 in PO and 0.75 h +/- 0.48 in IM). The mean
      (+/- SD) relative bioavailability (PO compared to IM) was 83 +/- 20% and 63 +/-
      23% for S-ketoprofen and R-ketoprofen, respectively. CONCLUSIONS: Although some
      minor differences were detected in the ketoprofen enantiomer concentrations in
      plasma after PO and IM administration, they are probably not relevant in clinical
      use. Thus, the pharmacological effects of racemic ketoprofen should be comparable
      after intramuscular and oral routes of administration in growing pigs.

PMID- 22998767
TI  - Two-step one-pot synthesis of benzoannulated spiroacetals by Suzuki-Miyaura
      coupling/acid-catalyzed spiroacetalization.
AB  - Substituted benzoannulated spiroacetals were prepared from (2-haloaryl)alkyl
      alcohols and dihydropyranyl or dihydrofuranyl pinacol boronates using a Suzuki
      Miyaura coupling followed by an acid-catalyzed spirocyclization. Application of
      the reaction to a glycal boronate provides an approach to annulated spiroacetals
      in enantiopure form.

PMID- 22998768
TI  - Comparison between the prognostic value of the white blood cell differential
      count and morphological parameters of neutrophils and lymphocytes in severely
      injured patients for 7-day in-hospital mortality.
AB  - CONTEXT: Current laboratory parameters provide limited information about the
      prognosis of severely injured patients; therefore, novel laboratory parameters
      are needed. MATERIALS AND METHODS: We compared the morphological parameters of
      neutrophils and lymphocytes, and white blood cell (WBC) differential count
      between survivors and nonsurvivors within 7 days after admission. Multiple
      logistic regression analysis was conducted to identify independent prognostic
      factors for 7-day in-hospital mortality. RESULTS: Neutrophil cell size was
      significantly different between survivors and nonsurvivors (p = 0.04), whereas
      WBC count and differential were not significantly different. Multiple logistic
      regression showed that neutrophil cell size was a significant predictor of poor
      outcome. CONCLUSIONS: Neutrophil cell size at admission is a prognostic factor
      for 7-day in-hospital mortality in severely injured trauma patients, whereas
      conventional WBC count and differential have no prognostic value.

PMID- 22998769
TI  - Objective compliance and outcome measures should be used in trials of exercise
      interventions for Chronic Fatigue Syndrome.

PMID- 22998770
TI  - Altered gene and protein expression in liver of the obese spontaneously
      hypertensive/NDmcr-cp rat.
AB  - BACKGROUND: It is difficult to study the mechanisms of the metabolic syndrome in
      humans due to the heterogeneous genetic background and lifestyle. The present
      study investigated changes in the gene and protein profiles in an animal model of
      the metabolic syndrome to identify the molecular targets associated with the
      pathogenesis and progression of obesity related to the metabolic syndrome.
      METHODS: We extracted mRNAs and proteins from the liver tissues of 6- and 25-week
      old spontaneously hypertensive/NIH -corpulent rat SHR/NDmcr-cp (CP), SHR/Lean
      (Lean) and Wistar Kyoto rats (WKY) and performed microarray analysis and two
      dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix
      assisted laser desorption ionization time-of-flight tandem mass spectrometry
      (MALDI-TOF/TOF MS). RESULTS: The microarray analysis identified 25 significantly
      up-regulated genes (P < 0.01; log10 > 1) and 31 significantly down-regulated
      genes (P < 0.01; log10 < -1) in 6- and 25-week-old CP compared with WKY and Lean.
      Several of these genes are known to be involved in important biological processes
      such as electron transporter activity, electron transport, lipid metabolism, ion
      transport, transferase, and ion channel activity. MALDI-TOF/TOF MS identified 31
      proteins with +/-1.2 fold change (P < 0.05) in 6- and 25-week-old CP, compared
      with age-matched WKY and Lean. The up-regulated proteins are involved in
      metabolic processes, biological regulation, catalytic activity, and binding,
      while the down-regulated proteins are involved in endoplasmic reticulum stress
      related unfolded protein response. CONCLUSION: Genes with significant changes in
      their expression in transcriptomic analysis matched very few of the proteins
      identified in proteomics analysis. However, annotated functional classifications
      might provide an important reference resource to understand the pathogenesis of
      obesity associated with the metabolic syndrome.

PMID- 22998771
TI  - High shear treatment of concentrates and drying conditions influence the
      solubility of milk protein concentrate powders.
AB  - The solubility of milk protein concentrate (MPC) powders was influenced by the
      method used for preparing the concentrate, drying conditions, and the type of
      dryer used. Increasing total solids of the ultrafiltered concentrates (23% total
      solids, TS) by diafiltration to 25% TS or evaporation to 31% TS decreased the
      solubility of MPC powders (80-83% protein, w/w dry basis), with ultrafiltration
      followed by evaporation to higher total solids having the greater detrimental
      effect on solubility. High shear treatment (homogenisation at 350/100 bar,
      microfluidisation at 800 bar or ultrasonication at 24 kHz, 600 watts) of
      ultrafiltered and diafiltered milk protein concentrates prior to spray drying
      increased the nitrogen solubility of MPC powders (82% protein, w/w dry basis). Of
      the treatments applied, microfluidisation was the most effective for increasing
      nitrogen solubility of MPC powders after manufacture and during storage.
      Manufacture of MPC powders (91% protein, w/w dry basis) prepared on two different
      pilot-scale dryers (single stage or two stage) from milk protein concentrates
      (20% TS) resulted in powders with different nitrogen solubility and an altered
      response to the effects of microfluidisation. Microfluidisation (400, 800 and
      1200 bar) of the concentrate prior to drying resulted in increased long term
      solubility of MPC powders that were prepared on a single stage dryer but not
      those produced on a two stage spray dryer. This work demonstrates that
      microfluidisation can be used as a physical intervention for improving MPC powder
      solubility. Interactions between the method of preparation and treatment of
      concentrate prior to drying, the drying conditions and dryer type all influence
      MPC solubility characteristics.

PMID- 22998772
TI  - Intravenous hemostatic nanoparticles increase survival following blunt trauma
      injury.
AB  - Trauma is the leading cause of death for people ages 1-44, with blood loss
      comprising 60-70% of mortality in the absence of lethal CNS or cardiac injury.
      Immediate intervention is critical to improving chances of survival. While there
      are several products to control bleeding for external and compressible wounds,
      including pressure dressings, tourniquets, or topical materials (e.g., QuikClot,
      HemCon), there are no products that can be administered in the field for internal
      bleeding. There is a tremendous unmet need for a hemostatic agent to address
      internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS
      NPs) that reduce bleeding times by ~50% in a rat femoral artery injury model.
      Here, we investigated their impact on survival following administration in a
      lethal liver resection injury in rats. Administration of these hemostatic
      nanoparticles reduced blood loss following the liver injury and dramatically and
      significantly increased 1 h survival from 40 and 47% in controls (inactive
      nanoparticles and saline, respectively) to 80%. Furthermore, we saw no
      complications following administration of these nanoparticles. We further
      characterized the nanoparticles' effect on clotting time (CT) and maximum clot
      firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical
      measurement of whole-blood coagulation. Clotting time is significantly reduced,
      with no change in MCF. Administration of these hemostatic nanoparticles after
      massive trauma may help staunch bleeding and improve survival in the critical
      window following injury, and this could fundamentally change trauma care.

PMID- 22998775
TI  - Prostaglandin reductase 2 modulates ROS-mediated cell death and tumor
      transformation of gastric cancer cells and is associated with higher mortality in
      gastric cancer patients.
AB  - Various prostanoids and peroxisome proliferator-activated receptor gamma
      (PPARgamma) ligands play an important role in gastric cancer. Previously, we
      demonstrated that prostaglandin reductase 2 (PTGR2) catalyzes the reduction of
      the PPARgamma ligand 15-keto-PGE(2) into 13,14-dihydro-15-keto-PGE(2). Here, we
      present functional data and clinical relevance for the role of PTGR2 in gastric
      cancer. Using lentiviral technology in AGS and SNU-16 gastric cancer cell lines,
      we either down-regulated or overexpressed PTGR2. In vitro analysis showed that
      PTGR2 knockdown resulted in decreased proliferation rate and colony formation,
      and in vivo xenograft models showed slower growth of tumors. Mechanistically,
      PTGR2 knockdown induced cell death, altered mitochondrial function, and increased
      reactive oxygen species production, which led to activation of ERK1/2 and caspase
      3, with increased Bcl-2 and suppressed Bax expression. PTGR2 overexpression
      showed the opposite outcomes. Clinically, immunopathological staining showed
      strong PTGR2 expression in the gastric tumor portion, relative to nearby nontumor
      portions, and its expression negatively correlated with survival of patients with
      intestinal-type gastric cancer. Finally, in contrast to PTGR2-overexpressing
      cells, PTGR2-knockdown cells were more sensitive to cisplatin and 5-fluorouracil.
      Taken together, our findings not only provide functional and mechanistic evidence
      of the involvement of PTGR2 in gastric cancer, but also provide clinical
      observations affirming the significance of PTGR2 in gastric cancer and suggesting
      that PTGR2-target based therapy is worth further evaluation.

PMID- 22998776
TI  - Thyroid stimulating hormone increases iodine uptake by thyroid cancer cells
      during BRAF silencing.
AB  - BACKGROUND: The BRAF(V600E) mutation is present in 62% of radioactive iodine
      resistant thyroid tumors and is associated with downregulation of the sodium
      iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHr). We sought
      to evaluate the combined effect of BRAF inhibition and TSH supplementation on
      (131)I uptake of BRAF(V600E)-mutant human thyroid cancer cells. MATERIALS AND
      METHODS: WRO cells (a BRAF(V600E)-mutant follicular-derived papillary thyroid
      carcinoma cell line) were transfected with small interfering RNA targeting BRAF
      for 72 h in a physiological TSH environment. NIS and TSHr expression were then
      evaluated at three levels: gene expression, protein levels, and (131)I uptake.
      These three main outcomes were then reassessed in TSH-depleted media and media
      supplemented with supratherapeutic concentrations of TSH. RESULTS: NIS gene
      expression increased 5.5-fold 36 h after transfection (P = 0.01), and TSHr gene
      expression increased 2.8-fold at 24 h (P = 0.02). NIS and TSHr protein levels
      were similarly increased 48 and 24 h after transfection, respectively. Seventy
      two hours after BRAF inhibition, (131)I uptake was unchanged in TSH-depleted
      media, increased by 7.5-fold (P < 0.01) in physiological TSH media, and increased
      by 9.1-fold (P < 0.01) in supratherapeutic TSH media. CONCLUSIONS: The combined
      strategy of BRAF inhibition and TSH supplementation results in greater (131)I
      uptake than when either technique is used alone. This represents a simple and
      feasible approach that may improve outcomes in patients with radioactive iodine
      resistant thyroid carcinomas for which current treatment algorithms are
      ineffective.

PMID- 22998778
TI  - The occurrence of pathogenic bacteria in some ships' ballast water incoming from
      various marine regions to the Sea of Marmara, Turkey.
AB  - The composition and frequency of antibiotic resistance of pathogenic bacteria,
      the abundance of heterotrophic aerobic bacteria (HPC) and possible in-situ use of
      chromogenic agar were investigated in the ships' ballast water coming from
      different regions of the world to the Sea of Marmara, Turkey for the first time.
      The samples that were taken from 21 unit ships coming from various marine
      environments of the Southern China Sea, the Atlantic Ocean, the Mediterranean and
      the Black Sea to the Sea of Marmara, Turkey in 2009 and 2010 were tested. 38
      bacteria species, 27 of them pathogenic bacteria belonging to 17 familia, were
      detected. Vibrio cholera was not detected in the samples. However, the presence
      of a high number of HPC, including a cocktail of pathogenic bacteria showed that
      the ships carry a potential risk for the Sea of Marmara.

PMID- 22998777
TI  - Scratching the surface of allergic transfusion reactions.
AB  - Allergic transfusion reactions (ATRs) are a spectrum of hypersensitivity
      reactions that are the most common adverse reaction to platelets and plasma,
      occurring in up to 2% of transfusions. Despite the ubiquity of these reactions,
      little is known about their mechanism. In a small subset of severe reactions,
      specific antibody has been implicated as causal, although this mechanism does not
      explain all ATRs. Evidence suggests that donor, product, and recipient factors
      are involved, and it is possible that many ATRs are multifactorial. Further
      understanding of the mechanisms of ATRs is necessary so that rationally designed
      and cost-effective prevention measures can be developed.

PMID- 22998782
TI  - Building global partnerships in infection prevention: a report from APIC Badger
      and the Nairobi Infection Control Nurses Chapter.
AB  - An international partnership between Wisconsin and Kenya was established after a
      serendipitous meeting with a newly formed infection control organization in
      Nairobi, Kenya, the Nairobi Infection Control Nurses Chapter (NICNC).
      Establishment of a sister chapter partnership between a Wisconsin Association for
      Professionals in Infection Control and Epidemiology chapter (APIC Badger) and the
      NICNC provided an opportunity to share resources. Although there are many
      barriers to developing infection prevention and control programs in Kenya, some
      needs can be met through such partnerships.

PMID- 22998715
TI  - Mortality after surgery in Europe: a 7 day cohort study.
AB  - BACKGROUND: Clinical outcomes after major surgery are poorly described at the
      national level. Evidence of heterogeneity between hospitals and health-care
      systems suggests potential to improve care for patients but this potential
      remains unconfirmed. The European Surgical Outcomes Study was an international
      study designed to assess outcomes after non-cardiac surgery in Europe. METHODS:
      We did this 7 day cohort study between April 4 and April 11, 2011. We collected
      data describing consecutive patients aged 16 years and older undergoing inpatient
      non-cardiac surgery in 498 hospitals across 28 European nations. Patients were
      followed up for a maximum of 60 days. The primary endpoint was in-hospital
      mortality. Secondary outcome measures were duration of hospital stay and
      admission to critical care. We used chi(2) and Fisher's exact tests to compare
      categorical variables and the t test or the Mann-Whitney U test to compare
      continuous variables. Significance was set at p<0.05. We constructed multilevel
      logistic regression models to adjust for the differences in mortality rates
      between countries. FINDINGS: We included 46,539 patients, of whom 1855 (4%) died
      before hospital discharge. 3599 (8%) patients were admitted to critical care
      after surgery with a median length of stay of 1.2 days (IQR 0.9-3.6). 1358 (73%)
      patients who died were not admitted to critical care at any stage after surgery.
      Crude mortality rates varied widely between countries (from 1.2% [95% CI 0.0-3.0]
      for Iceland to 21.5% [16.9-26.2] for Latvia). After adjustment for confounding
      variables, important differences remained between countries when compared with
      the UK, the country with the largest dataset (OR range from 0.44 [95% CI 0.19
      1.05; p=0.06] for Finland to 6.92 [2.37-20.27; p=0.0004] for Poland).
      INTERPRETATION: The mortality rate for patients undergoing inpatient non-cardiac
      surgery was higher than anticipated. Variations in mortality between countries
      suggest the need for national and international strategies to improve care for
      this group of patients. FUNDING: European Society of Intensive Care Medicine,
      European Society of Anaesthesiology.

PMID- 22998783
TI  - Molecular analysis and susceptibility patterns of methicillin-resistant
      Staphylococcus aureus strains causing community- and health care-associated
      infections in the northern region of Palestine.
AB  - BACKGROUND: Community acquired methicillin-resistant Staphylococcus aureus (CA
      MRSA) is a major global problem. This study attempted to investigate the
      prevalence of nasal carriage of Staphylococcus aureus and methicillin-resistant
      Staphylococcus aureus (MRSA) strains among 360 healthy university students at An
      Najah National University, Palestine. For the purpose of comparing the
      staphylococcal cassette chromosome methicillin resistant determinant (SCCmec)
      type of MRSA, 46 clinical MRSA isolates were also included in this study.
      METHODS: Susceptibility testing was performed by the disc diffusion method. The
      genetic association of MRSA isolates was investigated by SCCmec typing. A
      selected number of isolates were also used to amplify and sequence mecA. RESULTS:
      Nasal carriage of S aureus was found in 86 of 360 students (24%). MRSA accounted
      for 9% of S aureus isolates. All 86 strains of S aureus were sensitive to
      vancomycin. Resistance to penicillin G, amoxicillin/clavulanic acid,
      ciprofloxacin, erythromycin, and clindamycin was found in 98%, 93%, 33%, 23%, and
      12% of the isolates, respectively. Resistance rates of the MRSA isolates were as
      follows: 100% resistant to penicillin G and amoxicillin/clavulanic acid, 96% to
      ethromycin, 52% to clindamycin, and 48% to ciprofloxacin. No vancomycin-resistant
      isolates were identified. In our study, nearly half (52%) of the MRSA isolates
      belonged to SCCmec types IVa and V. However, SCCmec types II and III are
      represented by 48%, whereas SCCmec type I was completely absent. CONCLUSION: The
      findings of this study indicate the existence of SCCmec type IVa in both student
      nasal carriers and health care settings. This emphasizes the need for
      implementation of a revised set of control measures in both settings. Moreover,
      the rational prescription of appropriate antibiotics should also be considered.

PMID- 22998781
TI  - Core outcome measures for opioid abuse liability laboratory assessment studies in
      humans: IMMPACT recommendations.
AB  - A critical component in development of opioid analgesics is assessment of their
      abuse liability (AL). Standardization of approaches and measures used in
      assessing AL have the potential to facilitate comparisons across studies,
      research laboratories, and drugs. The goal of this report is to provide consensus
      recommendations regarding core outcome measures for assessing the abuse potential
      of opioid medications in humans in a controlled laboratory setting. Although many
      of the recommended measures are appropriate for assessing the AL of medications
      from other drug classes, the focus here is on opioid medications because they
      present unique risks from both physiological (e.g., respiratory depression,
      physical dependence) and public health (e.g., individuals in pain) perspectives.
      A brief historical perspective on AL testing is provided, and those measures that
      can be considered primary and secondary outcomes and possible additional outcomes
      in AL assessment are then discussed. These outcome measures include the
      following: subjective effects (some of which comprise the primary outcome
      measures, including drug liking; physiological responses; drug self
      administration behavior; and cognitive and psychomotor performance. Before
      presenting recommendations for standardized approaches and measures to be used in
      AL assessments, the appropriateness of using these measures in clinical trials
      with patients in pain is discussed.

PMID- 22998784
TI  - Associations between bacterial contamination of health care workers' hands and
      contamination of white coats and scrubs.
AB  - BACKGROUND: Uniforms are potential reservoirs for hospital organisms, potentially
      reinfecting the hands of health care workers (HCWs). The study aimed to determine
      the association between the bacterial contamination of HCWs' hands and uniforms
      (white coats and scrubs). METHODS: HCWs working in 5 intensive care units had
      cultures obtained from their hands and uniforms (white coats or scrubs).
      Pathogens were defined as any gram-negative bacilli, Staphylococcus aureus, and
      enterococci. RESULTS: Bacterial growth was detected on 103 hands (86%); 13 (11%)
      grew S aureus, 7 (6%) grew Acinetobacter spp, 2 (2%) grew enterococci, and 83
      (70%) grew only skin flora. The presence of pathogens on the hands was associated
      with a greater likelihood of the presence of pathogens on white coats (kappa =
      0.81; P < .001), but not on scrubs (kappa = 0.31; P = .036). Similarly, the
      presence of Acinetobacter on HCWs' hands was associated with a greater likelihood
      of Acinetobacter contamination of white coats (kappa = 0.70; P < .001), but not
      of scrubs (kappa = 0.36; P = .024). CONCLUSIONS: Contamination of provider's
      hands with pathogens or Acinetobacter baumannii was associated with contamination
      of white coats. This association was not observed between hands and scrubs,
      however.

PMID- 22998785
TI  - Duration of colonization by extended-spectrum beta-lactamase-producing
      Enterobacteriaceae after hospital discharge.
AB  - BACKGROUND: The duration of gastrointestinal colonization with extended-spectrum
      beta-lactamase-producing Enterobacteriaceae (ESBL-E) may play a major role in the
      spread of these organisms. We evaluated the time to, and factors associated with,
      ESBL-E clearance after hospital discharge. METHODS: We retrospectively reviewed
      prospective surveillance results obtained over 14 years in a 1,000-bed hospital.
      The surveillance collected demographic, hospital stay, microbiologic, and outcome
      data. An automatic alert system identified readmitted patients with prior ESBL-E
      carriage. ESBL-E clearance was defined as a negative rectal screening sample at
      readmission with no new positive clinical sample during the stay. Variables
      associated with ESBL-E clearance were identified using a Cox model. RESULTS: We
      included 1,884 patients with 2,734 admissions. Four hundred forty-eight patients
      with readmission screening formed the basis for the study. Of 448 patients with 1
      to 16 readmissions, 180 (40%) were persistent carriers. The median time to ESBL-E
      clearance was 6.6 months. Variables independently associated with clearance was
      having the first positive culture in a screening sample only (adjusted hazard
      ratio, 1.31; 95% confidence interval, 1.02-1.69; P = .04) and period 2005-2010
      (hazard ratio, 1.88; 95% confidence interval, 1.33-2.67; P < .01). CONCLUSION: We
      found a long duration of ESBL-E carriage after hospital discharge. An automatic
      alert system was useful for identifying, screening, and isolating previous ESBL-E
      carriers.

PMID- 22998787
TI  - Mid- and long-term results of the treatment of infrainguinal arterial occlusive
      disease with precuffed expanded polytetrafluoroethylene grafts compared with vein
      grafts.
AB  - BACKGROUND: Prosthetic grafts for lower-extremity bypass have limited patency
      compared with autologous vein grafts. Precuffed expanded polytetrafluoroethylene
      (ePTFE) grafts alter the geometry of the distal hood to improve patency. This
      study reports the authors' long-term results on the use of precuffed ePTFE grafts
      for infrainguinal bypasses in patients with arterial occlusive disease and
      compares these with results of reversed great saphenous vein grafts (rSVG).
      METHODS: A retrospective review of billing codes identified 101
      polytetrafluoroethylene (PTFE) and 47 rSVG bypasses performed over a 6-year
      period. Femoral to below-knee popliteal and femoral to tibial bypasses were
      analyzed. Data collected consisted of risk factors, Rutherford classification,
      bypass inflow and outflow, runoff vessels, patency, amputation, and death.
      Primary end points consisted of primary, assisted-primary, and secondary patency
      along with limb salvage. RESULTS: Mean age of the patients was 76 years in the
      PTFE group and 69.8 years in the rSVG group. For femoral to below-knee popliteal
      bypasses, primary patency at 1, 3, and 5 years in the PTFE group was 76.9%,
      48.7%, and 43.3%, respectively, compared with 77.1%, 77.1%, and 77.1%,
      respectively, in the rSVG group (P = 0.225). Secondary patency was 89.2%, 70.9%,
      and 50.6% in the PTFE group compared with 84.4%, 84.4%, and 84.4% in the rSVG
      group (P = 0.269). Limb salvage was similar in the PTFE compared with the rSVG
      group (97.7%, 90.5%, and 79.4% vs. 83.3%, 83.3%, and 83.3%; P = 0.653). For
      femoral to tibial bypasses, primary patency in the PTFE group at 1, 3, and 5
      years was 57.1%, 40.4%, and 22.1%, respectively, compared with 67.4%, 67.4%, and
      50.6%, respectively, for the rSVG group (P = 0.246). Secondary patency was 75.5%,
      44.9%, and 22.7% in the PTFE group compared with 91.8%, 91.8%, and 52.5% in the
      rSVG group (P = 0.022). Limb salvage at 1, 3, and 5 years was 79.2%, 55.7%, and
      55.7%, respectively, in the PTFE group compared with 96.4%, 96.4%, and 64.3%,
      respectively, in the rSVG group (P = 0.046). CONCLUSIONS: Precuffed ePTFE grafts
      demonstrate similar 1-year patency to that of rSVG. However, mid- and long-term
      patency is reduced compared with saphenous vein grafts (SVG), especially to
      tibial targets. PTFE grafts to the popliteal demonstrate limb salvage rates
      similar to those of SVG. In the tibial vessels, limb salvage rates for PTFE
      grafts are significantly worse compared with SVG.

PMID- 22998788
TI  - Varicocele in younger as risk factor for inguinal hernia and for chronic venous
      disease in older: preliminary results of a prospective cohort study.
AB  - BACKGROUND: Varicocele, inguinal hernia, and chronic venous insufficiency are
      often associated. Varicocele has its maximum prevalence in younger age, whereas
      hernia and chronic venous disease appear later. The aim of this study was to
      analyze the relationship between these conditions. METHODS: A prospective cohort
      study was conducted, consisting of two groups of male patients. Group A comprised
      patients with varicocele, whereas group B comprised those with problems other
      than varicocele. Both groups were followed over time and were assessed for the
      onset of signs and symptoms related to inguinal hernia and chronic venous
      disease. RESULTS: Preliminary results showed a positive correlation between the
      presence of varicocele in younger and the possible risk of hernia and/or chronic
      venous disease in later age. CONCLUSIONS: Preliminary results suggest that
      varicocele in younger age appears to be an early marker of progression for a
      connective tissue-related disease in later age.

PMID- 22998786
TI  - How to blast osteoblasts? Novel dicarba analogues of amylin-(1-8) to treat
      osteoporosis.
AB  - When administered in vivo, amylin (1-8) stimulates osteoblast proliferation
      increasing bone volume and bone strength. The native cyclic octapeptide amylin (1
      8) is unstable, however, it provides an attractive framework for the creation of
      more stable, orally active synthetic analogues using various peptidomimetic
      techniques. On-resin ring closing metathesis (RCM) on the olefinic side chains of
      allylglycine residues and lysine moieties functionalized with an allyloxycarbonyl
      (Alloc) group, was used to prepare novel carba-bridged surrogates of the
      disulfide bridge between Cys/2 and Cys/7 in amylin-(1-8). Commercially available
      N(alpha)-Fmoc N(epsilon)-Alloc protected lysine was used as a convenient
      substrate for Grubbs' ring closing metathesis. Analogues of amylin-(1-8) prepared
      by cyclization of allylglycine residues that also contained proline residues at
      either position 4 or 6, or both, were also prepared to investigate the effect of
      proline as a 'kink-inducing' residue on the efficiency of the RCM reaction. Of
      the nine novel alkene-bridged analogues prepared, five showed promising
      biological activity in a proliferation study in primary foetal rat osteoblasts at
      physiological concentrations. Two of these analogues were chosen for further in
      vivo evaluation.

PMID- 22998789
TI  - Use of unconventional dialysis access in patients with no viable alternative.
AB  - BACKGROUND: Hemodialysis patients who have exhausted all of the conventionally
      used veins for vascular access, including arteriovenous fistula, arteriovenous
      graft, and traditional catheter access sites, present a challenge to the treating
      physician. Transhepatic and translumbar inferior vena cava catheters have been
      used in these patients who have no other access site option. The objective of the
      study was to examine our experience with translumbar and transhepatic approach
      for catheter-based hemodialysis access in patients who have exhausted all other
      options. METHODS: A retrospective review was performed from June 2000 to May 2011
      of all patients who underwent transhepatic or translumbar inferior vena cava
      catheter placement for the purpose of hemodialysis. Data abstracted included
      previous access procedures, duration of use and patency of dialysis catheters,
      catheter-related complications, and mortality. RESULTS: Seven patients were
      identified. Four patients underwent transhepatic access and three underwent
      translumbar access. Five patients were female and two were male. The mean age was
      44 years. The etiology of renal failure was diabetes in four patients, congenital
      hypoplastic kidneys in two patients, and acute glomerulonephritis in one patient.
      A mean of 14 (range: 11-18) dialysis access procedures were performed before
      catheter placement by transhepatic/translumbar interventions. The initial device
      service interval for all patients ranged from 15 to 658 days, with a mean of 295
      days and a median of 245 days. Total access site service interval ranged from 15
      to 790 days, with a mean of 380 days and a median of 245 days. CONCLUSION:
      Translumbar and transhepatic venous access is a viable long-term alternative
      route for catheter-based hemodialysis access in patients who have exhausted
      conventional options.

PMID- 22998790
TI  - Composite stent-grafts are not associated with increased endoleak or
      reintervention rates after endovascular abdominal aneurysm repair.
AB  - BACKGROUND: Although present-generation endografts have expanded the indications
      for endovascular abdominal aneurysm repair, arterial anatomy frequently dictates
      the use of a combination of commercially available endografts and components for
      successful aneurysm repair. This study sought to determine whether there was an
      increase in endoleak or secondary intervention rates in individuals treated with
      composite endografts compared with noncomposite, or standard, endografts.
      METHODS: From 1999 to 2009, 421 endovascular abdominal aneurysm repairs were
      performed at a single institution. A total of 384 patients met criteria for
      inclusion, with at least one follow-up imaging study. Patients were then
      identified as having had a composite endograft, defined as any combination of two
      or more different commercially available endograft or stent components, versus a
      standard endograft. Primary outcomes measured were freedom from endoleak and
      secondary intervention. RESULTS: During the study period, 60 composite
      endograftings and 324 standard endograftings were performed. The groups were well
      matched for demographics, including age, gender, comorbidities, emergent need for
      procedure, and 30-day mortality (1.64% vs. 1.54%, nonsignificant). Median follow
      up was 16.3 months (range, 19 days to 8.5 years) and 10.2 months (range, 4 days
      to 8.7 years) for composite and standard endografts, respectively. There was no
      significant difference between the groups in either endoleak or secondary
      intervention rates. Median time to endoleak detection was 2.0 months (range, 2
      days to 3.9 years) for composite endografts and 2.8 months (range, 2 days to 6.9
      years) for standard endografts. Median time to secondary intervention was 7.0
      months (range, 4 days to 6.9 years) for composite endografts and 6.7 months
      (range, 1 day to 6.7 years) for standard endografts. CONCLUSIONS: Composite
      endografts, namely, the combination of different commercially available
      endografts or stents used for the treatment of aortic aneurysms, are not
      associated with increased mortality, endoleak, or secondary intervention rates
      compared with noncomposite endografts.

PMID- 22998791
TI  - Reinventing primaquine for endemic malaria.
AB  - After sixty years of continuous use, primaquine remains the only therapy licensed
      for arresting transmission and relapse of malaria. The US Army developed
      primaquine for soldiers in a wartime crisis setting. Dosing strategies suited to
      that narrow population were adopted without modification or validation for the
      broader population of humans exposed to risk of malaria. The poor suitability of
      these strategies in populations exhibiting greater vulnerability to hemolytic
      toxicity among glucose-6-phosphate dehydrogenase deficient patients has not been
      addressed. Primaquine requires chemotherapeutic reinvention delivering less
      threatening doses by leveraging unexplored co-drug synergies.

PMID- 22998792
TI  - Beat-to-beat estimation of the continuous left and right cardiac elastance from
      metrics commonly available in clinical settings.
AB  - INTRODUCTION: Functional time-varying cardiac elastances (FTVE) contain a rich
      amount of information about the specific cardiac state of a patient. However, a
      FTVE waveform is very invasive to directly measure, and is thus currently not
      used in clinical practice. This paper presents a method for the estimation of a
      patient specific FTVE, using only metrics that are currently available in a
      clinical setting. METHOD: Correlations are defined between invasively measured
      FTVE waveforms and the aortic and pulmonary artery pressures from 2 cohorts of
      porcine subjects, 1 induced with pulmonary embolism, the other with septic shock.
      These correlations are then used to estimate the FTVE waveform based on the
      individual aortic and pulmonary artery pressure waveforms, using the "other"
      dysfunction's correlations as a cross validation. RESULTS: The cross validation
      resulted in 1.26% and 2.51% median errors for the left and right FTVE
      respectively on pulmonary embolism, while the septic shock cohort had 2.54% and
      2.90% median errors. CONCLUSIONS: The presented method accurately and reliably
      estimated a patient specific FTVE, with no added risk to the patient. The cross
      validation shows that the method is not dependent on dysfunction and thus has the
      potential for generalisation beyond pulmonary embolism and septic shock.

PMID- 22998793
TI  - Parenting and depressive symptoms among adolescents in four Caribbean societies.
AB  - BACKGROUND: The strategies that parents use to guide and discipline their
      children may influence their emotional health. Relatively little research has
      been conducted examining the association of parenting practices to depressive
      symptoms among Caribbean adolescents. This project examines the association of
      parenting styles to levels of depressive symptoms among adolescents in Jamaica,
      the Bahamas, St. Kitts and Nevis, and St. Vincent. METHODS: Adolescents attending
      grade ten of academic year 2006/2007 in Jamaica, the Bahamas, St. Vincent, and
      St. Kitts and Nevis were administered the Parenting Practices Scale along with
      the BDI-II. Authoritative, Authoritarian, Permissive and Neglectful parenting
      styles were created using a median split procedure of the monitoring and
      nurturance subscales of the Parenting Practices Scale. Multiple regression
      analyses were used to examine the relationships of parenting styles to depressive
      symptoms. RESULTS: A wide cross-section of tenth grade students in each nation
      was sampled (n = 1955; 278 from Jamaica,  217 from the Bahamas, 737 St. Kitts and
      Nevis, 716 from St. Vincent; 52.1% females, 45.6% males and 2.3% no gender
      reported; age 12 to 19 years, mean = 15.3 yrs, sd = .95 yrs). Nearly half (52.1%)
      of all adolescents reported mild to severe symptoms of depression with 29.1%
      reporting moderate to severe symptoms of depression. In general, authoritative
      and permissive parenting styles were both associated with lower levels of
      depressive symptoms in adolescents. However, the relationship of parenting styles
      to depression scores was not consistent across countries (p < .05). In contrast
      to previous research on Caribbean parenting, caregivers in this study used a
      mixture of different parenting styles with the two most popular styles being
      authoritative and neglectful parenting. CONCLUSIONS: There appears to be an
      association between parenting styles and depressive symptoms that is
      differentially manifested across the islands of Jamaica, the Bahamas, St. Kitts
      and Nevis and St. Vincent.

PMID- 22998794
TI  - Measuring carotid intima-media thickness: extensive ultrasound protocols have
      value.

PMID- 22998795
TI  - Sancta simplicitas!

PMID- 22998796
TI  - Increasing member engagement.

PMID- 22998797
TI  - The scientific sessions as experienced by our travel grant recipients.

PMID- 22998798
TI  - A new award to recognize a new era in cardiovascular ultrasound.

PMID- 22998800
TI  - Desmoglein 1 expression on lung carcinoma cells in a patient with pemphigus
      foliaceus.

PMID- 22998801
TI  - Thoracic complications of rheumatoid disease.
AB  - Rheumatoid arthritis is a relatively common multisystem disease associated with
      significant mortality and morbidity. Thoracic disease, both pleural and
      pulmonary, is a frequent extra-articular manifestation of rheumatoid arthritis
      and responsible for approximately 20% of rheumatoid-associated mortality.
      Rheumatoid disease and its associated therapies can affect all compartments of
      the lung inciting a range of stereotyped pathological responses and it is not
      infrequent for multiple disease entities to co-exist. In some instances,
      development of pulmonary complications may precede typical rheumatological
      presentation of the disease and be the first indication of an underlying
      connective tissue disease. The spectrum of thoracic disease related to rheumatoid
      arthritis is reviewed.

PMID- 22998799
TI  - Positive allosteric modulation of TRPV1 as a novel analgesic mechanism.
AB  - BACKGROUND: The prevalence of long-term opiate use in treating chronic non-cancer
      pain is increasing, and prescription opioid abuse and dependence are a major
      public health concern. To explore alternatives to opioid-based analgesia, the
      present study investigates a novel allosteric pharmacological approach operating
      through the cation channel TRPV1. This channel is highly expressed in
      subpopulations of primary afferent unmyelinated C- and lightly-myelinated Adelta
      fibers that detect low and high rates of noxious heating, respectively, and it is
      also activated by vanilloid agonists and low pH. Sufficient doses of exogenous
      vanilloid agonists, such as capsaicin or resiniferatoxin, can
      inactivate/deactivate primary afferent endings due to calcium overload, and we
      hypothesized that positive allosteric modulation of agonist-activated TRPV1 could
      produce a selective, temporary inactivation of nociceptive nerve terminals in
      vivo. We previously identified MRS1477, a 1,4-dihydropyridine that potentiates
      vanilloid and pH activation of TRPV1 in vitro, but displays no detectable
      intrinsic agonist activity of its own. To study the in vivo effects of MRS1477,
      we injected the hind paws of rats with a non-deactivating dose of capsaicin,
      MRS1477, or the combination. An infrared diode laser was used to stimulate TRPV1
      expressing nerve terminals and the latency and intensity of paw withdrawal
      responses were recorded. qRT-PCR and immunohistochemistry were performed on
      dorsal root ganglia to examine changes in gene expression and the cellular
      specificity of such changes following treatment. RESULTS: Withdrawal responses of
      the capsaicin-only or MRS1477-only treated paws were not significantly different
      from the untreated, contralateral paws. However, rats treated with the
      combination of capsaicin and MRS1477 exhibited increased withdrawal latency and
      decreased response intensity consistent with agonist potentiation and
      inactivation or lesion of TRPV1-containing nerve terminals. The loss of nerve
      endings was manifested by an increase in levels of axotomy markers assessed by
      qRT-PCR and colocalization of ATF3 in TRPV1+ cells visualized via
      immunohistochemistry. CONCLUSIONS: The present observations suggest a novel, non
      narcotic, selective, long-lasting TRPV1-based approach for analgesia that may be
      effective in acute, persistent, or chronic pain disorders.

PMID- 22998802
TI  - Interannual and geographical reproducibility of the nutritional quality of milk
      fat from commercial grazing flocks.
AB  - The objective of the present work was to study the differences in the fatty acid
      (FA) composition of raw sheep milk fat under commercial milk production
      conditions throughout lactation, in two consecutive years. Particular attention
      was placed on the C18:2cis-9,trans-11 isomer, C18:1trans-11 acid, and unsaturated
      FA as the feeding regimen of 10 commercial flocks of latxa dairy sheep changed
      from indoor feeding to part-time grazing conditions (from early spring) as
      traditionally practiced in the Basque Country (Northern Spain). Farms located at
      an altitude of between 600 and 700 m, in two different geographical areas with
      different rainfall were selected. Milk samples were collected monthly from late
      January (indoor feeding) until mid-, or end of, June (outdoor feeding), during
      two consecutive years. In spite of some interannual variability (most likely due
      to large differences in rainfall), the evolution of individual FA throughout
      lactation was comparable between years, indicating that it was reproducible under
      commercial milk production conditions. The average concentrations of C18:2cis
      9,trans-11 isomer and C18:1trans-11 acid in milk from the commercial flocks
      increased about 200% during the transition period (end of March or early April
      until May), from indoor feeding (late January or early February until the end of
      March) to the outdoor period (early May to mid-June), remaining constant during
      the outdoor period (27.53 +/- 9.32 MUmol/g fat and 71.58 +/- 20.53 MUmol/g fat,
      respectively). Non-atherogenic FA comprised approximately 50% of all saturated FA
      at any time during lactation, whereas the milk atherogenicity index decreased
      significantly during the outdoor period. The Trolox-equivalent antioxidant
      capacity of the water-soluble milk fraction did not appear to be influenced by
      feeding management. The FA composition of cheeses made during the second year
      with milk from the indoor or outdoor periods reflected those of the corresponding
      milks. A principal components analysis clearly showed that differences in the
      milk FA composition were primarily due to outdoor grazing, with very little
      contribution from the geographical zone or the year.

PMID- 22998803
TI  - Antiadhesive and antibacterial multilayer films via layer-by-layer assembly of
      TMC/heparin complexes.
AB  - N-Trimethyl chitosan (TMC), an antibacterial agent, and heparin (HP), an
      antiadhesive biopolymer, were alternately deposited on modified polystyrene
      films, as substrates, to built antiadhesive and antibacterial multilayer films.
      The properties of the multilayer films were investigated by Fourier transform
      infrared spectroscopy, atomic force microscopy, scanning electron microscopy, and
      Kelvin force microscopy. In vitro studies of controlled release of HP were
      evaluated in simulated intestinal fluid and simulated gastric fluid. The initial
      adhesion test of  E. coli  on multilayer films surface showed effective
      antiadhesive properties. The in vitro antibacterial test indicated that the
      multilayer films of TMC/HP based on TMC80 can kill the  E. coli  bacteria.
      Therefore, antiadhesive and antibacterial multilayer films may have good
      potential for coatings and surface modification of biomedical applications.

PMID- 22998804
TI  - Eluding gravity: mankind's quest for flight.

PMID- 22998805
TI  - Very late stent thrombosis complicating a previously lost and partially crushed
      stent: demonstration by optical coherence tomography.
AB  - Stent thrombosis (ST) is the most dramatic complication of coronary stenting.
      Mechanisms of ST are multiple, including procedural and patient-related factors.
      A considerable burden of metal inside the coronary has been associated with ST as
      suggested by the higher rate of ST in case of multiple overlapping or complex two
      stents procedure in bifurcation lesions. However, occasional stent loss and
      failure to retrieve it may be a substrate of ST, especially if multiple layers of
      stent struts are incompletely crushed. Here, we describe a case of very late ST
      on a partially crushed stent previously lost inside the coronary circulation,
      using optical coherence tomography (OCT) for guidance during the procedure.

PMID- 22998806
TI  - 3 cases of primary intracranial hemorrhage associated with "Molly", a purified
      form of 3,4-methylenedioxymethamphetamine (MDMA).
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, or "Ecstasy" in tablet form) is a
      powerful sympathomimetic drug that is commonly perceived as safer than other
      stimulants such as methamphetamine or cocaine. "Molly" is a purified form of MDMA
      that is perceived by users as being even safer, as it is free of adulterants such
      as methamphetamine. Previously, all reports of intracranial hemorrhages in MDMA
      abusers were associated with coingestion of other sympathomimetic drugs, or with
      pre-existing cerebrovascular lesions. We describe a series of three young,
      otherwise healthy patients with various types of intracranial hemorrhages
      associated with "Molly" ingestion. All three patients underwent extensive workup
      including catheter angiography that did not demonstrate aneurysm, arteriovenous
      malformation, or vasculitis. We suggest that even the purified form of MDMA can
      cause serious intracranial hemorrhagic complications and should not be thought of
      as a safe recreational drug.

PMID- 22998809
TI  - Prevalence study in horses infected by Gasterophilus sp. in an eastern region of
      Poland.
AB  - A survey to determine current prevalence of Gasterophilus spp. (bot flies) in
      equids (n=400) at necropsy in slaughtered horses was conducted at the abattoir in
      Rawicz. The evaluation was performed according to sex, age, larval stages,
      severity of infestation and localization, respectively. Only Gasterophilus
      intestinalis and Gasterophilus nasalis were detected. The prevalence determined
      in the eastern part of Poland was of 47%. The high prevalence of this parasite
      infection in the Polish horse population confirms that Gasterophilosis spp. has
      to be taken into serious consideration and prophylactic measures might be
      indicated.

PMID- 22998808
TI  - Perceived unfairness and socioeconomic inequalities in functional decline: the
      Dutch SMILE prospective cohort study.
AB  - BACKGROUND: People in lower socioeconomic positions report worse health-related
      functioning. Only few examined whether perceptions of unfairness are particularly
      common in these people and whether this perceived unfairness relates to their
      subsequent poor health outcomes. We thus set out to examine the contribution of
      perceived unfairness to the higher risks of physical and mental dysfunction in
      men and women with a lower socioeconomic position. METHODS: Seven-year
      prospective cohort data from the Dutch SMILE study among 1,282 persons, 55 years
      old and older, were used. Physical and mental health-related functioning was
      measured with the SF-36, socioeconomic status with income and education, and the
      perception of unfairness with an extended new measure asking for such perceptions
      in both work and non-work domains. RESULTS: Perceived unfairness was more common
      in lower socioeconomic positions. Such perpection was related to both physical
      (odds ratio = 1.57 (95% confidence interval: 1.17-2.11)) and mental (1.47 (1.07
      2.03)) decline, while low socioeconomic position was only related to mental
      decline (1.33 (1.06-1.67)). When socioeconomic position and perceived unfairness
      were simultaneously controlled, odds ratios for both determinants decreased only
      very little. Socioeconomic position and perceived unfairness were for the largest
      part independently related to longitudinal health-related decline. CONCLUSIONS:
      The general perception of unfairness, at work and beyond work, might have
      implications for functional decline in middle and older age. We recommend that -
      rather than addressing and changing individual perceptions of unfairness--more
      research is needed to find out whether specific environments can be defined as
      unfair and whether such environments can be effectively tackled in an attempt to
      truly improve public health.

PMID- 22998810
TI  - Sonochemical synthesis and characterization of NiMoO4 nanorods.
AB  - NiMoO(4) nanorods have been successfully synthesized by sonochemical method
      process by using Ni(CH(3)COO)(2) . 4H(2)O and (NH(4))(6)Mo(7)O(24) . 4H(2)O as
      starting materials. Some parameters including ultrasonic power, ultrasonic
      irradiation time, stirring effect, solvent effect, and surfactant effect were
      investigated to reach optimum condition. The as synthesized nanostructures were
      characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM),
      transmittance electron microscopy (TEM), photoluminescence (PL) spectroscopy,
      Fourier transform infrared (FT-IR) spectra and energy dispersive X-ray
      microanalysis (EDX). Facile preparation and separation are important features of
      this route. This work has provided a general, simple, and effective method to
      control the composition and morphology of NiMoO(4) in aqueous solution, which
      will be important for inorganic synthesis methodology.

PMID- 22998811
TI  - Antineutrophil cytoplasmic auto-antibodies (ANCA) in autoimmune hepatitis and
      primary sclerosing cholangitis.

PMID- 22998812
TI  - End-to-side neurorrhaphy using an electrospun PCL/collagen nerve conduit for
      complex peripheral motor nerve regeneration.
AB  - In cases of complex neuromuscular defects, finding the proximal stump of a
      transected nerve in order to restore innervation to damaged muscle is often
      impossible. In this study we investigated whether a neighboring uninjured nerve
      could serve as a source of innervation of denervated damaged muscle through a
      biomaterial-based nerve conduit while preserving the uninjured nerve function.
      Tubular nerve conduits were fabricated by electrospinning a polymer blend
      consisting of poly(epsilon-caprolactone) (PCL) and type I collagen. Using a rat
      model of common peroneal injury, the proximal end of the nerve conduit was
      connected to the side of the adjacent uninjured tibial branch (TB) of the sciatic
      nerve after partial axotomy, and the distal end of the conduit was connected to
      the distal stump of the common peroneal nerve (CPN). The axonal continuity
      recovered through the nerve conduit at 8 weeks after surgery. Recovery of
      denervated muscle function was achieved, and simultaneously, the donor muscle,
      which was innervated by the axotomized TB also recovered at 20 weeks after
      surgery. Therefore, this end-to-side neurorrhaphy (ETS) technique using the
      electrospun PCL/collagen conduit appears to be clinically feasible and would be a
      useful alternative in instances where autologous nerve grafts or an adequate
      proximal nerve stump is unavailable.

PMID- 22998813
TI  - TATVHL peptide-grafted alginate/poly(gamma-glutamic acid) scaffolds with inverted
      colloidal crystal topology for neuronal differentiation of iPS cells.
AB  - The neuronal differentiation of induced pluripotent stem (iPS) cells in
      scaffolding biomaterials is an emerging issue in nervous regeneration and repair.
      This study presents the production of neuron-lineage cells from iPS cells in
      inverted colloidal crystal (ICC) scaffolds comprising alginate, poly(gamma
      glutamic acid) (gamma-PGA), and TATVHL peptide. The ability of iPS cells to
      differentiate toward neurons in the constructs was demonstrated by flow
      cytometeric sorting and immunochemical staining. The results revealed that
      hexagonally arrayed microspheres molded alginate/gamma-PGA hydrogel into ICC
      topology with adequate interconnected pores. An increase in the quantity of
      surface TATVHL peptide enhanced the atomic ratio of nitrogen and the adhesion
      efficiency of iPS cells in constructs. However, the effect of TATVHL peptide on
      the viability of iPS cells was insignificant. The adhesion and viability of iPS
      cells in ICC constructs was higher than those in freeform ones. TATVHL peptide
      raised the percentage of beta III tubulin-identified cells differentiating from
      iPS cells, indicating that TATVHL peptide stimulated the neuronal development in
      alginate/gamma-PGA ICC constructs. TATVHL peptide-grafted alginate/gamma-PGA ICC
      scaffolds can be promising for establishing nerve tissue from iPS cells.

PMID- 22998814
TI  - Long-term maintenance of mouse embryonic stem cell pluripotency by manipulating
      integrin signaling within 3D scaffolds without active Stat3.
AB  - We engineered an acellular biomimetic microenvironment to regulate stem cell fate
      and applied it to maintain mouse embryonic stem (ES) cell self-renewal. In the 3D
      environment formed using hydrogel scaffolds in which specific integrin ligation
      was provided, Stat3 activation by exogenous leukemia inhibitory factor (LIF) no
      longer acted as a limiting factor for stem cell self-renewal. Instead,
      simultaneous stimulation of integrins alpha(5)beta(1), alpha(v)beta(5),
      alpha(6)beta(1) and alpha(9)beta(1) within the 3D scaffold greatly increased Akt1
      and Smad 1/5/8 activation, which resulted in prolonged self-renewal of the ES
      cells. The ES cells exposed to the combined stimulation of the integrins for 4 wk
      in LIF-free 3D scaffolds maintained the spherical morphology of cell colonies
      without losing any activity of pluripotency. In conclusion, cell niche-specific
      integrin signaling within the 3D environment supported mouse ES cell self
      renewal, and the resulting integrin signaling replaced Stat3 with Akt1 and Smad
      1/5/8 as critical signals for mouse ES cell self-renewal.

PMID- 22998816
TI  - Efficient neuronal differentiation and maturation of human pluripotent stem cells
      encapsulated in 3D microfibrous scaffolds.
AB  - Developing an efficient culture system for controlled human pluripotent stem cell
      (hPSC) differentiation into selected lineages is a major challenge in realizing
      stem cell-based clinical applications. Here, we report the use of chitin-alginate
      3D microfibrous scaffolds, previously developed for hPSC propagation, to support
      efficient neuronal differentiation and maturation under chemically defined
      culture conditions. When treated with neural induction medium containing
      Noggin/retinoic acid, the encapsulated cells expressed much higher levels of
      neural progenitor markers SOX1 and PAX6 than those in other treatment conditions.
      Immunocytochemisty analysis confirmed that the majority of the differentiated
      cells were nestin-positive cells. Subsequently transferring the scaffolds to
      neuronal differentiation medium efficiently directed these encapsulated neural
      progenitors into mature neurons, as detected by RT-PCR and positive
      immunostaining for neuron markers betaIII tubulin and MAP2. Furthermore, flow
      cytometry confirmed that >90% betaIII tubulin-positive neurons was achieved for
      three independent iPSC and hESC lines, a differentiation efficiency much higher
      than previously reported. Implantation of these terminally differentiated neurons
      into SCID mice yielded successful neural grafts comprising MAP2 positive neurons,
      without tumorigenesis, suggesting a potential safe cell source for regenerative
      medicine. These results bring us one step closer toward realizing large-scale
      production of stem cell derivatives for clinical and translational applications.

PMID- 22998815
TI  - Influence of a three-dimensional, microarray environment on human cell culture in
      drug screening systems.
AB  - We have used a modified 3D cellular microarray platform for the high-throughput
      analysis of growth, cytotoxicity, and protein expression profile of a human
      hepatocellular carcinoma cell line, HepG2, in alginate. The results obtained were
      compared to analogous studies in 2D and 3D environments at the microtiter scale.
      The antiproliferative effects of four drugs, tamoxifen, 5-fluorouracil,
      doxorubicin, and amitriptyline, were studied as a function of seeding density in
      the three different culture platforms. The chemosensitivity of HepG2 cells to all
      four compounds decreased substantially with increasing cell number in the 2D and
      3D microtiter-based cultures, while no seeding density dependence was observed in
      the IC(50) values obtained in the 3D microarray culture platform. These results
      can be rationalized based on the development of confluence-dependent resistance
      in cultures where proliferation is restricted by cell-cell contacts and nutrient
      availability, as is the case for both of the microtiter-based cultures.
      Additionally, further development of an on-chip, in-cell immunofluorescence assay
      provided quantitative data on the levels of specific target proteins involved in
      proliferation, adhesion, angiogenesis and drug metabolism, and was used to
      compare expression profiles between 2D and 3D environments. The up-regulation of
      several CYP450 enzymes, beta1-integrin and vascular endothelial growth factor
      (VEGF) in the 3D microarray cultures suggests that this platform provides a more
      in vivo-like environment allowing cells to approach their natural phenotype.

PMID- 22998817
TI  - Report on childhood obesity in China (9): sugar-sweetened beverages consumption
      and obesity.
AB  - OBJECTIVE: To explore the associations between sugar-sweetened beverage (SSB)
      consumption and obesity as well as obesity-related cardiometabolic disorders
      among children in China. METHODS: A total of 6974 (boys 3558, girls 3412)
      children aged 6-13 years participated in the study. Each participant's height,
      weight, waist circumference, fasting glucose, triglycerides, total cholesterol,
      high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol
      were measured. The type of beverage consumption was determined using a self
      administered questionnaire. RESULTS: SSBs were consumed regularly by 46.1% of the
      children. The prevalence [adjusted odds ratio (95% confidence internal (CI)] of
      obesity was 7.6% [as the reference group (ref.)], 10.1% [1.36(1.07, 1.74)], and
      11.6% [1.46(1.21, 1.75)], among children who regularly drank milk, other
      beverages and SSBs, respectively. Regularly drinking SSBs elevated the likelihood
      of abdominal obesity [adjusted odds ratio (95% CI): 1.36 (1.17, 1.59)]. The
      prevalence [adjusted odds ratio (95% CI)] of obesity among children who regularly
      drank sports/caloric beverages, carbonated beverages, sweet tea, and plant
      protein beverages was 16.8% [2.00(1.31, 3.07)], 12.7% [1.52(1.23, 1.88)], 11.5%
      [1.52(1.18, 1.95)], and 10.4% [1.41(1.03, 1.94)], respectively, which was higher
      than that of regular milk drinkers [7.6 % (ref.)]. The prevalence [adjusted odds
      ratio (95% CI)] of abdominal obesity among children who regularly drank sweet
      tea, fruit/vegetable juices, and carbonated beverages was 17.7% [1.55(1.26,
      1.90)], 16.2% [1.36(1.09, 1.70)], and 15.3% [1.24(1.03, 1.50)], respectively,
      which was much higher than that of regular milk drinkers [12.8% (ref.)].
      CONCLUSIONS: Regular SSB consumption was positively related to obesity and
      abdominal obesity. This relationship should be investigated further using a
      longitudinal study design.

PMID- 22998818
TI  - Report on childhood obesity in China (10): association of sleep duration with
      obesity.
AB  - OBJECTIVES: To explore the association of sleep duration with obesity among
      children in urban areas of China. METHODS: A total of 6 576 children (3 293 boys
      and 3 283 girls) aged 7-11 years were randomly selected from 36 primary schools
      in 6 metropolitan cities in China. A 7-day Physical Activity Recall was used to
      assess the sleep duration and physical activity level. The height, weight, waist
      circumference (WC) and percentage of body fat (%BF, as determined by
      bioelectrical impedance analysis technique) were measured by following the
      standardized operation procedures. The information on demography, lifestyle and
      eating habits was collected with a self-administered questionnaire from
      participants and their parents. RESULTS: The average sleep duration per night in
      the children was 9.7 h with the decreasing trends along with the increase of age
      (P < 0.05). The sleep duration was negatively associated with body mass index
      (BMI) and WC in both boys and girls after adjustment for confounders (beta value 
      0.23 and -0.82 for boys, -0.24 and -0.91 for girls, respectively, P < 0.01).
      However, no significant association of sleep duration with %BF was found.
      Children who slept less than 9.0 h per night had a higher risk for overweight and
      obesity (OR = 1.29, 95% CI: 1.01, 1.64) and abdominal obesity (OR=1.38, 95% CI:
      1.04, 1.83) as compared with those who slept for 10.0-10.9 h. CONCLUSIONS: Short
      sleep duration is associated with obesity. It is important to ensure adequate
      sleep duration of children and foster their healthy lifestyle at an early stage
      of life.

PMID- 22998819
TI  - Visceral fat area, waist circumference and metabolic risk factors in abdominally
      obese Chinese adults.
AB  - OBJECTIVE: To examine the association of visceral adiposity as measured by VFA
      and WC with lipid and glucose metabolic biomarkers in abdominally obese Chinese
      adults, and to assess whether WC could be an indicator of visceral fat. METHODS:
      WC and VFA were measured in 155 overweight and obese adults. A fasting blood
      sample was collected from participant (n = 118) whose VFA > or = 100 cm2 for
      analyses of lipid and glucose profile. The relationship between VFA and WC and
      biomarkers was investigated. RESULTS: WC and VFA were significantly interrelated.
      The coincidence rate of abdominal obesity determined by Japanese VFA and Chinese
      WC criteria increased across age quartiles in women from 51.7% to 96.2%. A large
      WC was associated significantly with low HDL-cholesterol concentration (P < 0.01)
      and the association was weakened by additional control of VFA. WC and VFA were
      positively associated with glucose, hemoglobin A1c and insulin concentrations (P
      < 0.05 except for the association of VFA with insulin: P < 0.01), and all the
      associations were not significant by additional control of either WC or VFA. As
      WC quartiles increased, significant stepwise increments in triglyceride, glucose,
      hemoglobin A1c and insulin and descent in HDL-cholesterol were observed. However,
      triglyceride and HDL-cholesterol were not significantly different when compared
      across VFA quartiles. CONCLUSION: Higher visceral fat was associated with an
      adverse lipid and glucose profile. WC can be a moderate predictor for visceral
      fat and provides a feasible measurement to estimate glucose metabolic risks.
      Further studies are warranted to establish age-specific WC cutoffs.

PMID- 22998820
TI  - A survey of urolithiasis in young children fed infant formula contaminated with
      melamine in two townships of Gansu, China.
AB  - OBJECTIVE: To determine the prevalence of urolithiasis in young children fed
      infant formula (IF) contaminated with melamine, and the association between IF
      consumption and urolithiasis. DESIGN: A total of 2 733 children < or = 3 years of
      age on September 1, 2008 in two townships of Gansu Province, China were studied.
      Cases of urolithiasis were diagnosed by ultrasonography. Milk product consumption
      was determined by their caregivers. Remaining IF samples were tested for melamine
      and cyanuric acid. RESULTS: Of 2 733 eligible children in the two townships, 2
      186 (80%) were enrolled in our study. Overall, 16.6% (362) of 2 186 children had
      urolithiasis. The prevalence was 24.6% in children exclusively fed Sanlu brand
      IF, 9.7% in those fed other IF, and 8.5% in those fed exclusively on other milk
      products. For children exclusively breast-fed, no urolithiasis was found (P <
      0.05). The prevalence of urolithiasis was 11.4% in children fed 400 g of Sanlu
      IF, rising to 37.5% in children fed over 25 600 g. Of 48 Sanlu IF samples, 91.7%
      contained melamine (median = 1 800 ppm; range = 45-4 700) and 66.7% contained
      cyanuric acid (median = 1.2 ppm; range = 0.4-6.3). Melamine was also detected in
      22.2% of 36 other brand IF (median = 27.5 ppm, range = 4-50). CONCLUSIONS:
      Urolithiasis was associated with melamine-contaminated IF. Although one product
      caused most morbidity, other milk products may have also contributed to the
      outbreak.

PMID- 22998821
TI  - Association of catalase genotype with oxidative stress in the predication of
      colorectal cancer: modification by epidemiological factors.
AB  - OBJECTIVE: This paper aims to assess the interaction between common variations in
      catalase (CAT) polymorphic gene and environmental factors for antioxidant defense
      enzyme in modulating individual susceptibility to colorectal cancer (CRC).
      METHODS: A case-control study with 880 colorectal cancer cases and 848 controls
      was conducted to investigate whether variations in the catalase (CAT) gene, one
      of the genes involved in scavenging oxidative stress, influenced susceptibility
      to CRC. RESULTS: The interaction between life style and genotypes as well as with
      their effects on colorectal cancer was deduced from the present study.
      Significant difference (P = 0.01) was identified in the distribution of CAT
      genotype between the colorectal cancer cases and the controls. The CRC cases had
      significantly lower mean activity than the controls (P < 0.01). Correlation
      analyses revealed statistically significant correlations between CAT activity and
      CAT genotype (P < 0.01). CONCLUSION: The risk of CRC was associated with smoking,
      low vegetable consumption, high pork and poultry consumptions, and low or high
      BMI. This is the first study reporting an association of polymorphism CAT-21A > T
      with colorectal cancer. Low CAT activity was associated with an increased risk of
      CRC; however, no evidence was found to support an association between CAT-21A > T
      polymorphism and CRC risk.

PMID- 22998822
TI  - Analysis of the results of two nationwide surveys on Clonorchis sinensis
      infection in China.
AB  - OBJECTIVE: To examine Clonorchis sinensis infection in China and evaluate the
      effectiveness of efforts to prevent and control it, two nationwide surveys were
      undertaken in 31 provinces, autonomous regions, and municipalities (PAMs) during
      1988-92 (the 1990 survey) and during 2001-04 (the 2003 survey). METHODS: During
      the period 2001-04, two sampling methods were applied. The first method repeated
      the stratified cluster random sampling used in the 1990 survey; the second method
      applied two-characteristic stratified cluster random sampling in 27 PAMs-the 2003
      endemic area (EA) survey. The Kato-Katz thick smear method was used for the
      nationwide survey. RESULTS: The infection rates of Clonorchis sinensis in the
      1990 and 2003 surveys were 0.311% and 0.579%, respectively. The infection rate
      was 2.40% in the 2003 EA survey, and it was estimated that 12.49 million people
      in China were infected with Clonorchis sinensis. CONCLUSION: The 2003 survey
      showed that the standardized infection rate of Clonorchis sinensis increased by
      74.85% compared with the 1990 survey. The infection rate in males was higher than
      in females; the infection rate among people eating raw fish or eating out
      frequently was higher than among those who did not.

PMID- 22998823
TI  - Contamination of live virus during tissue homogenizing by ultrasonic processor
      and tissue disperser.
AB  - OBJECTIVE: To quantitatively evaluate the contamination area and risk of a live
      pathogen during tissue homogenization by either ultrasonic processor or tissue
      disperser. METHODS: A recombinant Herpes Simplex Virus (rHSV) containing GFP gene
      was used as the index virus, and fresh liver tissue from healthy mice was used as
      simulated specimen. After 10% liver homogenate was mixed with rHSV (100
      TCID50/0.1 mL) in a 5 mL tube, the stability of rHSV in liver homogenate and
      influences of an ultrasonic processor and a tissue disperser on viral infectivity
      were determined by GFP expressions in cell cultures. The contaminating areas of
      live viruses during homogenization were evaluated by a cell culture-based
      sedimentary. The contamination radii were counted by measurement of the distance
      between the operator and the farthest GFP positive well. RESULTS: The infectivity
      of rHSV in 10% liver homogenate maintained almost unchanged after it was
      incubated at room temperature for 30 min. Treatment with an ultrasonic processor
      clearly dropped down the virus infectivity, while a disperser not. Obvious spills
      and slashes of live viruses were observed in processes of homogenization with
      those two apparatuses. The contamination radii are positively related with sample
      volume, output energy of operator and handling time. CONCLUSION: Homogenizing
      infectious samples with an ultrasonic processor and a tissue disperser at
      commonly used conditions caused obvious spills and splashes of live viruses,
      which possesses high risk to induce Laboratory acquired infections (LAIs).

PMID- 22998824
TI  - Oxidative stress and apoptotic changes of rat cerebral cortical neurons exposed
      to cadmium in vitro.
AB  - OBJECTIVE: To investigate the cytotoxic mechanism of cadmium (Cd) on cerebral
      cortical neurons. METHODS: The primary cultures of rat cerebral cortical neurons
      were treated with different concentrations of cadmium acetate (0, 5, 10, and 20
      micromol/L), and then the cell viability, apoptosis, ultrastructure,
      intracellular [Ca2+], and reactive oxygen species (ROS) levels, mitochondrial
      membrane potential (delta psi), activities of catalase (CAT) and superoxide
      dismutase (SOD) were measured. RESULTS: A progressive loss in cell viability and
      an increased number of apoptotic cells were observed. In addition, Cd-induced
      apoptotic morphological changes in cerebral cortical neurons were also
      demonstrated by Hoechst 33258 staining. Meanwhile, ultrastructural changes were
      distortion of mitochondrial cristae and an unusual arrangement. Simultaneously,
      elevation of intracellular [Ca2+]i and ROS levels, depletion of Delta Psi were
      revealed in a dose-dependent manner during the exposure. Moreover, CAT and SOD
      activities in the living cells increased significantly. CONCLUSION: Exposure of
      cortical neurons to different doses of Cd led to cellular death, mediated by an
      apoptotic mechanism, and the apoptotic death induced by oxidative stress may be a
      potential reason. And the disorder of intracellular homeostasis caused by
      oxidative stress and mitochondrial dysfunction may be a trigger for apoptosis in
      cortical neurons.

PMID- 22998825
TI  - Relationship between cognition function and hippocampus structure after long-term
      microwave exposure.
AB  - OBJECTIVE: To analyze the effects of long-term microwave exposure on hippocampal
      structure and function in the rat. METHODS: Experiments were performed on 184
      male Wistar rats (three exposure groups and a sham group). Microwaves were
      applied daily for 6 min over 1 month at average power densities of 2.5, 5, and 10
      mW/cm2. Learning and memory abilities were assessed by Morris water maze. High
      performance liquid chromatography was used to detect neurotransmitter
      concentrations in the hippocampus. Hippocampal structures were observed by
      histopathological analysis. RESULTS: Following long-term microwave exposure there
      was a significant decrease in learning and memory activity in the 7 d, 14 d, and
      1 m in all three microwave exposure groups. Neurotransmitter concentrations of
      four amino acids (glutamate, aspartic acid, glycine, and gamma-aminobutyric acid)
      in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the
      10 mW/cm2 group. There was evidence of neuronal degeneration and enlarged
      perivascular spaces in the hippocampus in the microwave exposure groups. Further,
      mitochondria became swollen and cristae were disordered. The rough endoplasmic
      reticulum exhibited sacculated distension and there was a decrease in the
      quantity of synaptic vesicles. CONCLUSION: These data suggest that the
      hippocampus can be injured by long-term microwave exposure, which might result in
      impairment of cognitive function due to neurotransmitter disruption.

PMID- 22998826
TI  - The effect of n-hexane on the gonad toxicity of female mice.
AB  - OBJECTIVE: To investigate the toxic effects of n-hexane on the Ganod of female
      mice. METHODS: n-Hexane was administered to four groups of mice by inhalation at
      doses of 0, 3.0, 15.1, and 75.8 mL/m3 respectivelyfor five weeks. Each group
      consisted of 10 mice, of which half were injected in first with 10 IU of pregnant
      mare serum gonadotrophin (PMSG) on the 33rd days, and then with 10 IU of human
      chorionic gonadotrophin (HCG) 48 hrs later. After the treatment, mouse sera were
      sampled and ovulating hormone (LH), follicle-stimulating hormone (FSH), estradiol
      (E2), and progesterone (P4) levels were measured by electrochemiluminescence
      immunoassays (ECLIA). In each group, the right ovaries of the non-super-ovulated
      mice were stained with hematoxylin and eosin while ovaries on the left side were
      prepared with the TUNEL method in order to detect apoptotic cells. RESULTS: The
      duration of the diestrus stage decreased significantly (P < 0.05) in the 75.8
      mL/m3 group. All super-ovulated mice in each treatment group produced fewer eggs
      than those in the control group (P < 0.05). The number of follicles in ovaries in
      the 75.8 mL/m3 group was smaller compared with the control group (P < 0.05).The
      serum P4 levels in each treatment group were lower than those in the control
      group (F = 6.196, P < 0.01). The cell apoptotic rate in the 75.8 mL/m3 group was
      higher (P < 0.05). CONCLUSION: n-Hexane may have directly mediated via
      alterations hormone secretion and promoted granulosal cell apoptotic, which may
      be one of the important mechanisms for n-hexane induced mouse ovary impairment.

PMID- 22998827
TI  - Altered expression of matrix metalloproteinases and tight junction proteins in
      rats following PEMF-induced BBB permeability change.
AB  - OBJECTIVE: To investigate the expression of occludin, ZO-1, MMP-2, and MMP-9 in
      cerebral microvasculature following Pulse Electromagnetic Field (PEMF) induced
      BBB permeability change. METHODS: Sprague-Dawley rats were randomized into PEMF
      and sham exposed groups (n = 8). After exposure to PEMF at 0.5, 1, 3, 6, and 12
      h, BBB permeability was measured by Evans-Blue extravasation. The expression of
      occludin, ZO-1, MMP-2, and MMP-9 were detected by real-time quantitative reverse
      transcriptase PCR and western blotting. MMP-2 and MMP-9 activity were detected by
      EnzChek gelatinase assay. RESULTS: Compared with the sham group, PEMF exposure
      led to increased permeability of the BBB to EB, which was prolonged after
      exposure. BBB permeability became progressively more severe, and recovered at 6
      h. The gene and protein expression of occludin and ZO-1 were significantly
      decreased, while MMP-2 and MMP-9 expression were significantly increased after
      exposure to PEMF. All levels of expression recovered 12 h following PEMF.
      CONCLUSION: Changes to BBB permeability were related to the alteration expression
      of tight junction proteins and matrix metalloproteinase after exposure to PEMF.

PMID- 22998828
TI  - Construction and secretory expression of beta-galactosidase gene from
      Lactobacillus bulgaricus in Lactococcus lactis.
AB  - OBJECTIVE: This study is to examine the secretion effects of beta-galactosidase
      in Lactococcus lactis. METHODS: The usp45 and beta-galactosidase genes were
      cloned and inserted into plasmid pMG36e to obtain the recombinant plasmid pMG36e
      usp-lacZ. This recombinant plasmid was transformed into both Escherichia coli
      DH5alpha and L. lactis MG1363. The enzyme activity, gene sequencing, SDS-PAGE and
      hereditary stability were assessed and studied. RESULTS: The lacZ gene inserted
      into plasmids pMG36e-usp-lacZ was 99.37% similar to the GenBank sequence, and SDS
      PAGE revealed an evident idio-strap at 116 KDa between L. lactis MG1363/pMG36e
      usp-lacZ in both supernatant and cell samples. Beta-Galactosidase activity
      measured 0.225 U/mL in L. lactis pMG36e-usp-lacZ transformants, and its secretion
      rate was 10%. The plasmid pMG36e-usp-lacZ appeared more stable in MG1363.
      CONCLUSION: The authors concluded that these new recombinant bacteria well
      expressed and secreted beta-galactosidase, indicating that the beta-galactosidase
      expression system was successfully constructed, and this might provide a new
      solution for management of lactose intolerance specifically and promote the use
      of gene-modified organisms as part of the food-grade plasmid in general.

PMID- 22998829
TI  - Inhibitory effect of extracellular polysaccharide EPS-II from Pseudoalteromonas
      on Candida adhesion to cornea in vitro.
AB  - OBJECTIVE: Fungal keratitis (FK) is a vision-threatening infection, whose
      treatment requires more effective and safer anti-fungal agent exploitation
      urgently. With this aim, we focused on the effect of an extracellular
      polysaccharide on fungal adhesion to human corneal epithelial cells. METHODS: We
      performed the cytotoxicity assays of the extracellular polysaccharide EPS-II from
      an antarctic bacterium Pseudoaltermonas and evaluated its inhibitory effect on
      Candida albicans cells' adherence to human corneal epithelial cells (HCECs).
      RESULTS: EPS-II, which displayed minor cytotoxicity but also promoted
      proliferation of HCECs, could inhibit the adherence of yeast cells to HCECs in a
      dose-dependent manner. EPS-II could also suppress the subsequent PI3K/AKT
      signaling pathway, and thereby decrease the expression of early inflammatory
      cytokines. CONCLUSIONS: Extracellular polysaccharide EPS-II was suggested as a
      new natural agent for attenuating FK.

PMID- 22998830
TI  - Toxicity of sodium fluoride to Caenorhabditis elegans.
AB  - OBJECTIVE: To investigate the toxic effect of sodium fluoride (NaF) on the
      nematode Caenorhabditis elegans (C. elegans). METHODS: Adult C. elegans were
      exposed to different concentrations of NaF (0.038 mmol/L, 0.38 mmol/L, and 3.8
      mmol/L) for 24 h. To assess the physiological effects of NaF, the brood size,
      life span, head thrashes, and body bend frequency were examined. Reactive oxygen
      species (ROS) and cell apoptosis were detected as parameters of biochemical
      response. The gene expressions were determined by real-time polymerase chain
      reaction (PCR) to assess the molecular-level response. RESULTS: At the
      physiological level, the brood size of C. elegans exposed to 0.038 mmol/L, 0.38
      mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 6%, 26%, and 28%
      respectively in comparison with the control group. The maximum life spans of C.
      elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of
      NaF were reduced by 3 days and 5 days, respectively. Head thrashes and body bend
      frequency both decreased with increasing concentrations of NaF. At the
      biochemical level, the production of ROS and the incidence of cell apoptosis
      increased with increasing concentrations of NaF (P < 0.05). At the molecular
      level, different concentrations of NaF exposure raised the expression of stress
      related genes, such as hsp16.1, sod-3, ctl-2, dhs-28, gst-1, and cep-1.
      CONCLUSION: NaF exposure could induce multiple biological toxicities to C.
      elegans in a concentration-dependent manner. These toxicities may be relevant to
      the oxidative stress induced by increased ROS production and accumulation in C.
      elegans.

PMID- 22998831
TI  - Laboratory evaluation of the molluscicidal activity of Pulsatilla chinensis
      (Bunge) Regel saponins against the snail Oncomelania hupensis.
AB  - OBJECTIVE: To observe the toxicity of Pulsatilla chinensis (Bunge) Regel saponins
      (PRS) against Oncomelania hupensis (O. hupensis). METHODS: O. hupensis snails
      were exposed to 40% and 80% of 24 h LC50 of PRS for 24 h, and then choline
      esterase (CHE), alanine aminotransferase (ALT), alkaline phosphatase (ALP),
      lactate dehydrogenase (LDH) activities in cephalopodium and liver of snails were
      determined. Niclosamide (NIC) was used as the reference molluscicide. Zebra fish
      lethality test was evaluated to non-target aquatic species of PRS. RESULTS: The
      molluscicidal activity of PRS (LC50 at 24 h: 0.48 mg/L) was similar to that of
      NIC (LC50 at 24 h: 0.16 mg/L). Significant alterations about CHE, ALP, and ALT
      activities both in the cephalopodium and the liver of snails were observed when
      O. hupensis was exposed to 40% and 80% LC50 of PRS or NIC for 24 h. PRS and NIC
      could not affect LDH activity in the cephalopodium and the liver. Lower toxicity
      to fish of PRS was observed up to the highest concentration tested than NIC.
      CONCLUSION: PRS, as compared with the reference molluscicide NIC, is thought to
      be used for the control of harmful vector snails safely.

PMID- 22998832
TI  - Inactivation of resistant Mycobacteria mucogenicum in water: chlorine resistance
      and mechanism analysis.
AB  - OBJECTIVE: To better understand the mechanism of chlorine resistance of
      mycobacteria and evaluate the efficiency of various disinfection processes.
      METHODS: Inactivation experiments of one strain Mycobacteria mucogenicum,
      isolated from a drinking water distribution system in South China were conducted
      with various chlorine disinfectants. Inactivation efficiency and disinfectant
      residual, as well as the formation of organic chloramines, were measured during
      the experiments. RESULTS: This strain of M. mucogenicum showed high resistance to
      chlorine. The CT values of 99.9% inactivation by free chlorine, monochloramine
      and chlorine dioxide were detected as 29.6 +/- 1.46, 170 +/- 6.16, and 10.9 +/
      1.55 min. (mg/L) respectively, indicating that chlorine dioxide exhibited
      significantly higher efficiency than free chlorine and monochloramine. It was
      also found that M. mucogenicum reacted with chlorine disinfectants more slowly
      than 5. aureus, but consumed more chlorine disinfectants during longer time of
      contact. Lipid analysis of the cell construction revealed that 95.7% of cell
      membrane lipid of M. mucogenicum was composed of saturated long chain fatty
      acids. Saturated fatty acids were regarded as more stable and more hydrophilic
      which enabled the cell membrane to prevent the diffusion of chlorine. CONCLUSION:
      It was concluded that different compositions of cell membrane might endow M.
      mucogenicum with a higher chlorine resistance.

PMID- 22998833
TI  - Effects of echinacoside on histio-central levels of active mass in middle
      cerebral artery occlusion rats.
AB  - OBJECTIVE: To investigate the effects of echinacoside on the extracellular
      striatal levels of norepinephrine (NE), dopamine (DA), homovanillic acid (HVA),
      3, 4-dihydroxyphenylethanoid acid (DOPAC), 5-hydroxyindoleacetic acid (HIAA), and
      5-hydroxytryptamine(5-HT) in middle cerebral artery occlusion (MCAO rats.
      METHODS: The middle cerebral artery was occluded in male Sprague-Dawley rats.
      Three days later microdialysis probes were placed into the right striatum of MCAO
      rat brains and the brains were perfused with Ringer's solution at a rate of 1.5
      microL/min. Cerebral microdialysates were collected every 30 minutes from awake
      and freely moving rats before assaying for NE, DA, HVA, DOPAC, HIAA, and 5-HT
      levels by reverse phase HPLC with electrochemistry. RESULTS: Three days after
      MCAO, the extracellular striatal levels of NE, DA, DOPAC, HIAA, HVA, and 5-HT of
      the MCAO rats increased significantly (at least P < 0.05 vs. control). However,
      simultaneous treatment with echinacoside (30.0 or 15.0 mg/kg) attenuated these
      increases (at least P < 0.05 vs. non-treated model rats). CONCLUSION: These
      results imply that echinacoside may protect striatal dopa minergic neurons from
      the injury induced by MCAO and may help prevent and treat cerebral ischemic
      diseases.

PMID- 22998834
TI  - Formation of DNA strand breaks in peripheral lymphocytes of rats after exposure
      to natural sunlight.
AB  - OBJECTIVE: This paper aims to evaluate the genotoxicity in peripheral blood
      lymphocytes of rats after exposure to sunlight at different time points of day in
      a tropical region of Brazil (5 degrees S, 42 degrees W). MATERIALS AND METHODS:
      Thirty Wistar-Hannover rats, three months old, were randomly divided into three
      groups of 10 animals each: Group I [control, without exposure to ultraviolet (UV)
      radiation], Group II (exposed to sunlight during 08:00 a.m. to 10:00 a.m.), and
      Group III (exposed to sunlight during 10:00 a.m. to 12:00 a.m.). After a week of
      exposure, peripheral blood samples were taken from the tail of these animals to
      prepare smears on two slides per animal. In 24 h after exposure to sunlight in
      Group III, a new collection was obtained to observe the repair activity. The
      alkaline comet assay was used in this study to evaluate the genotoxic activity of
      sunlight (P < 0.05). RESULTS: There was no statistical difference between Group I
      and II (P = 0.672). On the other hand, the exposure to sunlight in Group III
      showed genotoxic action in comparison to the other groups (P < 0.0001). Also,
      there was no significant repair in Group III R (P = 0.407). CONCLUSION: This
      study has shown a genotoxic potential of sunlight (UVA-B) in lymphocytes of
      mammals from 10:00 a.m. to 12:00 a.m., due to a higher intensity of UV in this
      tropical region.

PMID- 22998835
TI  - Lipoma mimicking a perforation.

PMID- 22998836
TI  - A rare cause of upper GI hemorrhage: an uncorrupted sponge migrating into the
      duodenal bulb (with video).

PMID- 22998837
TI  - Effects of radiation emitted by WCDMA mobile phones on electromagnetic
      hypersensitive subjects.
AB  - BACKGROUND: With the use of the third generation (3 G) mobile phones on the rise,
      social concerns have arisen concerning the possible health effects of radio
      frequency-electromagnetic fields (RF-EMFs) emitted by wideband code division
      multiple access (WCDMA) mobile phones in humans. The number of people with self
      reported electromagnetic hypersensitivity (EHS), who complain of various
      subjective symptoms such as headache, dizziness and fatigue, has also increased.
      However, the origins of EHS remain unclear. METHODS: In this double-blind study,
      two volunteer groups of 17 EHS and 20 non-EHS subjects were simultaneously
      investigated for physiological changes (heart rate, heart rate variability, and
      respiration rate), eight subjective symptoms, and perception of RF-EMFs during
      real and sham exposure sessions. Experiments were conducted using a dummy phone
      containing a WCDMA module (average power, 24 dBm at 1950 MHz; specific absorption
      rate, 1.57 W/kg) within a headset placed on the head for 32 min. RESULTS: WCDMA
      RF-EMFs generated no physiological changes or subjective symptoms in either
      group. There was no evidence that EHS subjects perceived RF-EMFs better than non
      EHS subjects. CONCLUSIONS: Considering the analyzed physiological data, the
      subjective symptoms surveyed, and the percentages of those who believed they were
      being exposed, 32 min of RF radiation emitted by WCDMA mobile phones demonstrated
      no effects in either EHS or non-EHS subjects.

PMID- 22998838
TI  - The maintenance of cisplatin- and paclitaxel-induced mechanical and cold
      allodynia is suppressed by cannabinoid CB2 receptor activation and independent of
      CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy.
AB  - BACKGROUND: Chemotherapeutic agents produce dose-limiting peripheral neuropathy
      through mechanisms that remain poorly understood. We previously showed that
      AM1710, a cannabilactone CB2 agonist, produces antinociception without producing
      central nervous system (CNS)-associated side effects. The present study was
      conducted to examine the antinociceptive effect of AM1710 in rodent models of
      neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and
      paclitaxel). A secondary objective was to investigate the potential contribution
      of alpha-chemokine receptor (CXCR4) signaling to both chemotherapy-induced
      neuropathy and CB2 agonist efficacy. RESULTS: AM1710 (0.1, 1 or 5 mg/kg i.p.)
      suppressed the maintenance of mechanical and cold allodynia in the cisplatin and
      paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2
      antagonist AM630 (3 mg/kg i.p.), but not the CB1 antagonist AM251 (3 mg/kg i.p.),
      consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling
      with its receptor antagonist AMD3100 (10 mg/kg i.p.) failed to attenuate
      mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel.
      Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects
      of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of
      action. CONCLUSIONS: Our results indicate that activation of cannabinoid CB2
      receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct
      models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling
      does not contribute to the maintenance of chemotherapy-induced established
      neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors
      represent a promising therapeutic target for the treatment of toxic neuropathies
      produced by cisplatin and paclitaxel chemotherapeutic agents.

PMID- 22998839
TI  - Quantification of early adipose-derived stem cell survival: comparison between
      sodium iodide symporter and enhanced green fluorescence protein imaging.
AB  - OBJECTIVE: Strategies to overcome the problem of extensive early stem cell loss
      following transplantation requires a method to quantitatively assess their
      efficacy. This study compared the ability of sodium/iodide symporter (NIS) and
      enhanced green fluorescent protein (EGFP) imaging to monitor the effectiveness of
      treatments to enhance early stem cell survival. METHODS: Human adipose-derived
      stem cells (ADSCs) transduced with an adenoviral vector to express both NIS and
      EGFP were mixed with culture media (control), matrigel (matrigel group) or pro
      survival cocktail (PSC group), and 5*10(6) cells were injected into thigh muscles
      of C57BL/6 mice. Animals underwent serial optical imaging and (99m)TcO(4)(-)
      scintigraphy. Image-based EGFP fluorescence and (99m)TcO(4)(-) uptake was
      measured by region-of-interest analysis, and extracted tissues were measured for
      (99m)Tc activity. Fluorescent intensity measured from homogenized muscle tissue
      was used as reference for actual amount of viable ADSCs. RESULTS: ADSCs were
      efficiently transduced to express EGFP and NIS without affecting proliferative
      capacity. The absence of significant apoptosis was confirmed by annexin V FACS
      analysis and Western blots for activated caspase-3. Both fluorescence optical
      imaging and (99m)TcO(4)(-) scintigraphy visualized implanted cells in living mice
      for up to 5days. However, optical imaging displayed large variations in
      fluorescence intensity, and thus failed to detect difference in cell survival
      between groups or its change over time. In comparison, (99m)TcO(4)(-)
      scintigraphy provided more reliable assessment of within-in group donor cell
      content as well as its temporal change. As a result, NIS imaging was able to
      discern beneficial effects of matrigel and pro-survival cocktail treatment on
      early ADSC survival, and provided quantitative measurements that correlated to
      actual donor cell content within implanted tissue. CONCLUSION: NIS reporter
      imaging may be useful for noninvasively assessing the efficacies of strategies
      designed to improve early survival of transplanted stem cells.

PMID- 22998841
TI  - Efficient synthesis of a fluorine-18 labeled biotin derivative.
AB  - INTRODUCTION: The natural occurring vitamin biotin, also known as vitamin H or
      vitamin B(7), plays a major role in various metabolic reactions. Caused by its
      high binding affinity to the protein avidin with a dissociation constant of about
      10(-15)M the biotin-avidin system was extensively examined for multiple
      applications. We have synthesized a fluorine-18 labeled biotin derivative
      [(18)F]4 for a potential application in positron emission tomography (PET).
      METHODS: Mesylate precursor 3 was obtained by an efficient two-step reaction via
      a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible
      starting materials. [(18)F]4 was successfully synthesized by a nucleophilic
      radiofluorination of precursor 3. A biodistribution study by means of small
      animal PET imaging in wt-mice was performed and serum stability was examined.
      RESULTS: Compound [(18)F]4 was obtained from precursor compound 3 with an average
      specific activity of 16GBq/MUmol within 45min and a radiochemical yield of 45+/
      5% (decay corrected). [(18)F]4 demonstrated only negligible decomposition in
      human serum. A qualitative binding study revealed the high affinity of the
      synthesized biotin derivative to avidin. Blocking experiments with native biotin
      showed that binding was site-specific. Biodistribution studies showed that
      [(18)F]4 was cleared quickly and efficiently from the body by hepatobiliary and
      renal elimination. CONCLUSION: An efficient synthesis for [(18)F]4 was
      established. In vivo characteristics were determined and demonstrated the
      pharmacokinetic behaviour of [(18)F]4.

PMID- 22998840
TI  - PET imaging with 89Zr: from radiochemistry to the clinic.
AB  - The advent of antibody-based cancer therapeutics has led to the concomitant rise
      in the development of companion diagnostics for these therapies, particularly
      nuclear imaging agents. A number of radioisotopes have been employed for antibody
      based PET and SPECT imaging, notably 64Cu, 124I, 111In, and (99m)Tc; in recent
      years, however, the field has increasingly focused on 89Zr, a radiometal with
      near ideal physical and chemical properties for immunoPET imaging. In the review
      at hand, we seek to provide a comprehensive portrait of the current state of 89Zr
      radiochemical and imaging research, including work into the production and
      purification of the isotope, the synthesis of new chelators, the development of
      new bioconjugation strategies, the creation of novel 89Zr-based agents for
      preclinical imaging studies, and the translation of 89Zr-labeled
      radiopharmaceuticals to the clinic. Particular attention will also be dedicated
      to emerging trends in the field, 89Zr-based imaging applications using vectors
      other than antibodies, the comparative advantages and limitations of 89Zr-based
      imaging compared to that with other isotopes, and areas that would benefit from
      more extensive investigation. At bottom, it is hoped that this review will
      provide both the experienced investigator and new scientist with a full and
      critical overview of this exciting and fast-developing field.

PMID- 22998842
TI  - Towards an integrative approach to understanding quality of life in
      schizophrenia: the role of neurocognition, social cognition, and psychopathology.
AB  - The term "schizophrenia" refers to a debilitating group of disorders that usually
      results in a severely impaired quality of life (QoL). Symptomatology appears to
      have a substantial role in determining QoL, although the relationship between QoL
      and specific psychotic symptoms is still unclear and has demonstrated mixed
      results. Due to the intrinsic importance of social functioning in QoL, and the
      mediating effect of social cognition on social functioning, the aim of this study
      was to try to investigate QoL in schizophrenia, not only in terms of
      symptomatology, but also in consideration of potential neurocognitive and social
      cognitive contributing factors. METHODS: Twenty-eight clinically stable patients
      with schizophrenia performed a broad range of neurocognitive and social cognitive
      assessments, and also participated in a semi-structured interview of QoL,
      assessing four partially independent subdomains of QoL. A stepwise regression
      model was used to determine the best predictors of QoL, and additionally a
      mediator analysis was performed to test for the mediating power of social
      cognition on QoL. RESULTS: Negative symptoms, intelligence, executive functioning
      and social cognition all had some power in predicting QoL in schizophrenia.
      Though most interestingly, mental state reasoning was specifically found to be
      most strongly related with the Intrapsychic Foundation subdomain of QoL, whereas
      neurocognition and symptom severity were associated with other subdomains of QoL.
      CONCLUSIONS: The association between mental state reasoning and the more
      "internal" aspects of QoL in schizophrenia may reflect a specific role for social
      cognition in introspective and subjective judgments of one's own QoL, whereas
      neurocognition and negative symptomatology may be more predictive of the external
      or extrinsic aspects of QoL. In conclusion, social cognitive skills appear to
      play a crucial role in the experience of one's own subjective well-being, which
      could help to explain previous inconsistencies in the literature investigating
      QoL in schizophrenia.

PMID- 22998843
TI  - The structure of common mental disorders in incarcerated offenders.
AB  - BACKGROUND: Dimensional models of mental disorders in community-based
      epidemiological samples have consistently demonstrated correlated externalizing
      and internalizing factors underlying common mood, anxiety, and substance use
      disorders. However, such analyses tend to exclude populations such as prisoners
      and psychiatric inpatients. As these samples have been shown to have a much
      higher prevalence of mental disorders and comorbidity than community samples,
      whether the internalizing-externalizing structure of psychopathology will
      replicate in such samples is unknown. OBJECTIVES: The current study examined the
      consistency of this structure in a representative sample of 1837 prisoners
      through structural equation modeling of 10 common mental disorders along with a
      record-based index of antisocial behavior. METHOD: Diagnoses were determined by
      administration of the Composite International Diagnostic Interview 2.1. Data were
      analyzed via tetrachoric correlations using the weighted least squares estimator
      in exploratory and confirmatory factor analyses. RESULTS: Results revealed that a
      two-factor solution, entailing correlated internalizing and externalizing
      factors, displayed the best fit to the data. CONCLUSIONS: This study provides
      additional support for characterizing common psychopathology in terms of
      internalizing and externalizing factors.

PMID- 22998844
TI  - Is low affect consciousness related to the severity of psychopathology? A cross
      sectional study of patients with avoidant and borderline personality disorder.
AB  - OBJECTIVE: This study examined the relationships between affect consciousness
      (AC) and symptom distress, interpersonal problems, low self-esteem, and the
      number of PD traits in patients with avoidant personality disorder (APD) and
      borderline personality disorder (BPD). METHOD: Within the setting of a treatment
      trial, 52 patients with APD or BPD were examined with structured interviews and
      self-report questionnaires before treatment and at 3-year follow-up. The
      evaluations included the Affect Consciousness Interview, the SCID-II interview,
      the Symptom Checklist 90-R, the Circumplex of Interpersonal Problems, and the
      Index of Self-esteem. A low global level of AC was expected to be associated with
      the severity of psychopathology; a low AC for interest, joy, and tenderness was
      expected to be associated with social detachment; and a low AC for anger,
      contempt, and disgust was expected to be associated with nonassertiveness.
      RESULTS: A low AC was associated with interpersonal problems and low self-esteem,
      but not symptom distress or the number of fulfilled SCID-II criteria. Despite a
      significant reduction in the psychopathology based on most clinical variables,
      the associations measured at baseline were maintained after 3years. Examination
      of specific affect categories showed a pattern of convergent and discriminative
      relationships with different types of interpersonal problems. A low AC for
      pleasant affects was specifically related to communion problems, like cold,
      detached behavior, both at baseline and follow-up. In contrast, a low AC for self
      boundary affects was specifically related to agency problems, like non
      assertiveness, at follow-up. CONCLUSION: Our results showed that a low AC was
      associated with central domains of psychopathology in patients with PDs. This
      suggested that AC would be an important focus for treatment and further research
      in PDs. Future studies are needed to examine how AC is related to various forms
      of personality pathology.

PMID- 22998845
TI  - Usefulness of the International Personality Disorder Examination Screening
      Questionnaire for borderline and impulsive personality pathology in adolescents.
AB  - The aim of this study was to analyze the usefulness of the International
      Personality Disorder Examination Screening Questionnaire (IPDE-SQ) for
      identifying DSM-IV and ICD-10 Borderline and Impulsive personality disorders (PD)
      in Spanish adolescents. METHOD: The DSM-IV and ICD-10 IPDE-SQ screeners were used
      and compared with the diagnoses obtained with the IPDE semistructured interview
      in a sample of 125 adolescents treated in a psychiatric department. RESULTS: For
      primary screening, the cutoff point with the best combination of sensitivity and
      specificity for ICD-10 impulsive and borderline PDs was obtained with three
      positive items, whereas for DSM-IV borderline the best PD cut-off was five
      positive items. For secondary screening, the best option would be one item above
      the cut-off points proposed for primary screening. CONCLUSION: The 3-item cut-off
      point in the IPDE-SQ produces a high proportion of false positives on impulsive
      and borderline PDs in clinical adolescents. We propose several cut-off points,
      depending on whether the study is designed to perform primary or secondary
      screening.

PMID- 22998846
TI  - The flat-plate plant-microbial fuel cell: the effect of a new design on internal
      resistances.
AB  - Due to a growing world population and increasing welfare, energy demand
      worldwide is increasing. To meet the increasing energy demand in a sustainable
      way, new technologies are needed. The Plant-Microbial Fuel Cell (P-MFC) is a
      technology that could produce sustainable bio-electricity and help meeting the
      increasing energy demand. Power output of the P-MFC, however, needs to be
      increased to make it attractive as a renewable and sustainable energy source. To
      increase power output of the P-MFC internal resistances need to be reduced. With
      a flat-plate P-MFC design we tried to minimize internal resistances compared to
      the previously used tubular P-MFC design. With the flat-plate design current and
      power density per geometric planting area were increased (from 0.15 A/m2 to 1.6
      A/m2 and from 0.22 W/m2 to and 0.44 W/m2)as were current and power output per
      volume (from 7.5 A/m3 to 122 A/m3 and from 1.3 W/m3 to 5.8 W/m3). Internal
      resistances times volume were decreased, even though internal resistances times
      membrane surface area were not. Since the membrane in the flat-plate design is
      placed vertically, membrane surface area per geometric planting area is
      increased, which allows for lower internal resistances times volume while not
      decreasing internal resistances times membrane surface area. Anode was split into
      three different sections on different depths of the system, allowing to calculate
      internal resistances on different depths. Most electricity was produced where
      internal resistances were lowest and where most roots were present; in the top
      section of the system. By measuring electricity production on different depths in
      the system, electricity production could be linked to root growth. This link
      offers opportunities for material-reduction in new designs. Concurrent reduction
      in material use and increase in power output brings the P-MFC a step closer to
      usable energy density and economic feasibility.

PMID- 22998847
TI  - [3.0 T MRI with a high resolution protocol for the study of benign disease of the
      anus and rectum. Part one: High resolution protocol for 3.0 T MRI, anatomic
      review, benign tumors, and congenital or acquired alterations of the sphincter
      complex].
AB  - Benign anorectal disease comprises a broad group of processes with very diverse
      origins; these processes may be congenital or acquired as well as inflammatory or
      tumor related. However, benign anorectal disease has received less attention in
      the scientific literature than malignant disease. We present an image-based
      review of the most common benign diseases of the anus and rectum. In this first
      part, we review the anatomy of the region and provide a brief description of the
      peculiarities of the high resolution protocol that we use with 3.0 T MRI. We go
      on to describe the most common benign anorectal tumors and developmental cystic
      lesions, together with their differential diagnoses, as well as congenital and
      acquired anomalies of the anorectal sphincter complex. 

PMID- 22998848
TI  - Avian influenza transmission risks: analysis of biosecurity measures and contact
      structure in Dutch poultry farming.
AB  - In the 2003 epidemic of highly pathogenic avian influenza in Dutch poultry,
      between-farm virus transmission continued for considerable time despite control
      measures. Gaining more insight into the mechanisms of this spread is necessary
      for the possible development of better control strategies. We carried out an in
      depth interview study aiming to systematically explore all the poultry production
      activities to identify the activities that could potentially be related to virus
      introduction and transmission. One of the between-farm contact risks that were
      identified is the movement of birds between farms during thinning with violations
      of on-farm biosecurity protocols. In addition, several other risky management
      practices, risky visitor behaviours and biosecurity breaches were identified.
      They include human and fomite contacts that occurred without observing
      biosecurity protocols, poor waste management practices, presence of other animal
      species on poultry farms, and poor biosecurity against risks from farm
      neighbourhood activities. Among the detailed practices identified, taking cell
      phones and jewellery into poultry houses, not observing shower-in protocols and
      the exchange of unclean farm equipment were common. Also, sometimes certain
      protocols or biosecurity facilities were lacking. We also asked the interviewed
      farmers about their perception of transmission risks and found that they had
      divergent opinions about the visitor- and neighbourhood-associated risks. We
      performed a qualitative assessment of contact risks (as transmission pathways)
      based on contact type, corresponding biosecurity practices, and contact
      frequency. This assessment suggests that the most risky contact types are bird
      movements during thinning and restocking, most human movements accessing poultry
      houses and proximity to other poultry farms. The overall risk posed by persons
      and equipment accessing storage rooms and the premises-only contacts was
      considered to be medium. Most of the exposure risks are considered to be similar
      for layer and broiler farms. Our results, including those on farmer opinions, are
      relevant for the communication with farmers and poultry-related businesses about
      practices and risks. We conclude by providing recommendations for improvement of
      control strategies.

PMID- 22998850
TI  - Small proportions of actively-smoking patrons and high PM2.5 levels in southern
      California tribal casinos: support for smoking bans or designated smoking areas.
AB  - BACKGROUND: Nearly all California casinos currently allow smoking, which leads to
      potentially high patron exposure to secondhand tobacco smoke pollutants. Some
      argue that smoking restrictions or bans would result in a business drop, assuming
      > 50% of patrons smoke. Evidence in Nevada and responses from the 2008 California
      tobacco survey refute this assertion. The present study investigates the
      proportion of active smokers in southern California tribal casinos, as well as
      occupancy and PM(2.5) levels in smoking and nonsmoking sections. METHODS: We
      measured active-smoker and total-patron counts during Friday or Saturday night
      visits (two per casino) to smoking and nonsmoking gaming areas inside 11 southern
      California casinos. We counted slot machines and table games in each section,
      deriving theoretical maximum capacities and occupancy rates. We also measured
      PM(2.5) concentrations (or used published levels) in both nonsmoking and smoking
      areas. RESULTS: Excluding one casino visit with extremely high occupancy, we
      counted 24,970 patrons during 21 casino visits of whom 1,737 were actively
      smoking, for an overall active- smoker proportion of 7.0% and a small range of
      ~5% across casino visits (minimum of 5% and maximum of 10%). The differences in
      mean inter-casino active-smoker proportions were not statistically significant.
      Derived occupancy rates were 24% to 215% in the main (low-stakes) smoking-allowed
      slot or table areas. No relationship was found between observed active-smoker
      proportions and occupancy rate. The derived maximum capacities of nonsmoking
      areas were 1% to 29% of the overall casino capacity (most under 10%) and their
      observed occupancies were 0.1 to over 3 times that of the main smoking-allowed
      casino areas. Seven of twelve visits to nonsmoking areas with no separation had
      occupancy rates greater than main smoking areas. Unenclosed nonsmoking areas
      don't substantially protect occupants from PM2.5 exposure. Nonsmoking areas
      encapsulated inside smoking areas or in a separate, but unenclosed, area had
      PM(2.5) levels that were 10 to 60 MUg/m(3) and 6 to 23 MUg/m(3) higher than
      outdoor levels, respectively, indicating contamination from smoking. CONCLUSIONS:
      Although fewer than roughly 10% of casino patrons are actively smoking on
      average, these individuals substantially increase PM(2.5) exposure for all
      patrons in smoking and unenclosed nonsmoking areas. Nonsmoking areas may be too
      inconvenient, small, or undesirable to serve a substantial number of nonsmoking
      patrons. Imposing indoor smoking bans, or contained smoking areas with a maximum
      capacity of up to 10% of the total patronage, would offer protection from PM2.5
      exposures for nonsmoking patrons and reduce employee exposures.

PMID- 22998851
TI  - Birds, babies and blood.
AB  - This is an autobiographical review describing the author's career in immunology
      research and summarizing his current understanding of the areas involved.
      Contributions to autoimmunity, immune deficiency, transfusion immunology, HLA
      disease associations, reproductive immunology, cellular therapies, and innate
      immunity are included; also discussion of medical research ethics and various
      research-related activities.

PMID- 22998852
TI  - The relationship between happiness and intelligent quotient: the contribution of
      socio-economic and clinical factors.
AB  - BACKGROUND: Happiness and higher intelligent quotient (IQ) are independently
      related to positive health outcomes. However, there are inconsistent reports
      about the relationship between IQ and happiness. The aim was to examine the
      association between IQ and happiness and whether it is mediated by social and
      clinical factors. Method The authors analysed data from the 2007 Adult
      Psychiatric Morbidity Survey in England. The participants were adults aged 16
      years or over, living in private households in 2007. Data from 6870 participants
      were included in the study. Happiness was measured using a validated question on
      a three-point scale. Verbal IQ was estimated using the National Adult Reading
      Test and both categorical and continuous IQ was analysed. RESULTS: Happiness is
      significantly associated with IQ. Those in the lowest IQ range (70-99) reported
      the lowest levels of happiness compared with the highest IQ group (120-129).
      Mediation analysis using the continuous IQ variable found dependency in
      activities of daily living, income, health and neurotic symptoms were strong
      mediators of the relationship, as they reduced the association between happiness
      and IQ by 50%. CONCLUSIONS: Those with lower IQ are less happy than those with
      higher IQ. Interventions that target modifiable variables such as income (e.g.
      through enhancing education and employment opportunities) and neurotic symptoms
      (e.g. through better detection of mental health problems) may improve levels of
      happiness in the lower IQ groups.

PMID- 22998853
TI  - Immediate impact of successful percutaneous mitral valve commissurotomy on
      echocardiographic measures of right ventricular contractility.
AB  - BACKGROUND: Functional analysis of the right ventricle cannot be reliably
      evaluated by conventional echocardiography, because of its complex geometry and
      load dependence of ejection phase indices. The Tei index, dP/dt, and myocardial
      acceleration during isovolumic contraction are parameters of right ventricular
      (RV) contractility unaffected by RV geometry. However, the effect of loading
      conditions on these parameters is controversial. The aim of this study was to
      examine how afterload reduction observed after percutaneous transverse mitral
      commissurotomy (PTMC) in patients with mitral stenosis affects these measures of
      RV contractility. METHODS: Fifty-eight patients (mean age, 30.0 +/- 8.3 years
      seven men, 52 women) with isolated rheumatic mitral stenosis, eight of whom had
      atrial fibrillation, were studied prospectively before and 24 to 48 hours after
      PTMC. RESULTS: Immediately after PTMC, mitral valve area increased from 1.0 +/-
      0.2 to 1.8 +/- 0.3 cm(2) (P = .0001). There was a significant decrease in
      systolic pulmonary artery pressure from 50.2 +/- 26.9 to 33.2 +/- 12.3 mm Hg (P =
      .0001), a decrease in the RV Tei index from 0.5 +/- 0.2 to 0.3 +/- 0.2 (P =
      .0001), and an increase in RV dP/dt from 321.0 +/- 59.9 to 494.6 +/- 139.5 mm
      Hg/sec (P = .0001). RV myocardial acceleration during isovolumic contraction and
      systolic velocity at the lateral tricuspid annulus assessed by Doppler tissue
      imaging did not change. There were weak positive correlations among the Tei
      index, dP/dt, and systolic pulmonary artery pressure before PTMC (respectively, r
      = 0.39, r = 0.28, and P = .02, P = .05) but not afterward (respectively, r =
      0.17, r = 0.02, and P = .20, P = .90). CONCLUSIONS: This study suggests that RV
      dP/dt and Tei index are weakly load dependent, whereas myocardial acceleration
      during isovolumic contraction is unaffected by acute change in RV afterload.

PMID- 22998854
TI  - Measurement of left atrial volume from transthoracic three-dimensional
      echocardiographic datasets using the biplane Simpson's technique.
AB  - BACKGROUND: Although left atrial volume (LAV) by two-dimensional (2D)
      echocardiography provides prognostic information, the misalignment of the 2D
      cutting plane of the left atrium could make the measurements inaccurate. The aim
      of this study was to test the hypothesis that LAV measurement from three
      dimensional (3D) echocardiographic data sets using the biplane Simpson's
      technique is a more reliable approach for measuring LAV. METHODS: The accuracy of
      3D echocardiographic LAV measurements was retrospectively determined in 20
      patients using multidetector computed tomography as a reference. LAV indexed to
      body surface area (LAVI) was measured using 2D and 3D echocardiography in 200
      other subjects. LAV determination by 2D echocardiography was performed using the
      biplane Simpson's method. A 3D determination of LAV was performed using
      quantitative software and the biplane Simpson's method using the anterior
      posterior and medial-lateral 2D views extracted from the 3D data sets. RESULTS:
      Although LAV using the 3D volumetric method (mean, 98 +/- 24 mL) was slightly but
      significantly lower than LAV on multidetector computed tomography (mean, 103 +/-
      23 mL), a significant correlation between the two methods (r = 0.97, P < .001)
      with acceptable limits of agreement was noted. The left atrial short-axis image
      extracted from the 3D data sets revealed an ellipsoid shape. Although a good
      correlation for LAVI was noted between the 2D biplane Simpson's method and the 3D
      volumetric method (r = 0.96, P < .001), the mean value of 2D echocardiographic
      LAVI was significantly greater compared with 3D echocardiographic LAVI, with a
      mean bias of 4.7 mL/m(2). An excellent correlation was noted between the 3D
      biplane Simpson's and 3D volumetric methods (r = 0.99, P < .001), with a lower
      bias (0.54 mL/m(2)) and limits of agreement of +/-5.8 mL/m(2). The time required
      for LAV analysis was significantly shorter with the 2D (mean, 82 +/- 7 sec) and
      3D (mean, 94 +/- 11 sec) biplane Simpson's methods (P < .01 vs 2D biplane
      Simpson's method) compared with the 3D volumetric methods (mean, 135 +/- 24 sec)
      (P < .01 vs 2D and 3D biplane Simpson's methods). CONCLUSIONS: The 2D biplane
      Simpson's method overestimates LAV because of the misalignment of the 2D cutting
      plane, and the 3D biplane Simpson's method is a practical and more reliable way
      to accurately determine LAV.

PMID- 22998855
TI  - Comparison of the updated 2011 appropriate use criteria for echocardiography to
      the original criteria for transthoracic, transesophageal, and stress
      echocardiography.
AB  - BACKGROUND: The aim of this study was to compare appropriateness designations as
      determined by the updated 2011 appropriate use criteria (AUC) for
      echocardiography with prior versions of the AUC for transthoracic
      echocardiographic (TTE) imaging, transesophageal echocardiographic (TEE) imaging,
      and stress echocardiographic (SE) imaging. An additional goal was to define
      relationships between appropriateness determinations and echocardiographic
      findings for each modality. METHODS: Previously published data sets of TTE, TEE,
      and SE studies were reclassified according to the 2011 AUC, and indication
      representation, appropriateness designations, and echocardiographic findings were
      compared with prior classifications according to the 2007 AUC for TTE and TEE
      imaging and the 2008 AUC for SE imaging. RESULTS: Overall, 2,247
      echocardiographic studies were analyzed. The 2011 AUC addressed the vast majority
      of studies (98%), a marked increase compared with prior versions of the AUC (89%)
      (P < .001). An increase in addressed studies was present in each
      echocardiographic modality (TTE imaging: n = 1,525, 98% vs 89%, P < .001; TEE
      imaging: n = 405, 99.7% vs 91%, P < .01; SE imaging: n = 289, 97% vs 88%, P <
      .01). Among all echocardiographic procedures, the 2011 AUC found a lower
      frequency of appropriate studies compared with prior AUC (82% vs 88%, P < .01),
      primarily because of new uncertain indications for TTE imaging. The frequency of
      inappropriate echocardiographic studies was unchanged (11%). Among all
      echocardiographic procedures, the 2011 AUC found appropriate studies to have more
      new abnormal echocardiographic findings compared with inappropriate studies (45%
      vs 13%, P < .001). Interestingly, 2011 AUC inappropriate TTE studies had fewer
      major new echocardiographic abnormalities than 2007 AUC inappropriate TTE studies
      (9% vs 17%, P = .04). CONCLUSIONS: The updated 2011 AUC for echocardiography
      encompass the vast majority of echocardiographic procedures in a university
      hospital practice, filling virtually all of the gaps identified in prior versions
      of the AUC for TTE, TEE, and SE imaging. The 2011 AUC also reasonably stratify
      the likelihood of finding an echocardiographic abnormality, demonstrating
      improvement compared with the prior AUC.

PMID- 22998856
TI  - Prospective randomized comparison of conventional stress echocardiography and
      real-time perfusion stress echocardiography in detecting significant coronary
      artery disease.
AB  - BACKGROUND: Although retrospective studies have suggested that myocardial
      perfusion and wall motion analysis with real-time myocardial contrast
      echocardiography (RTMCE) improves the detection of coronary artery disease (CAD)
      during dobutamine or exercise stress echocardiography, a prospective randomized
      comparison with conventional stress echocardiography that did not use RTMCE has
      not been performed. METHODS: A total of 1,776 patients with preserved resting
      left ventricular wall motion undergoing dobutamine or exercise stress
      echocardiography for suspicion of CAD were randomized to either non-RTMCE, for
      which contrast was used only for the approved indication of enhancing left
      ventricular opacification, or RTMCE, for which contrast infusion was used in all
      cases to examine both wall motion and myocardial perfusion. Comparisons in test
      positivity, and positive predictive value in those subsequently referred for
      quantitative coronary angiography, were performed. RESULTS: Patients randomized
      to RTMCE had significantly higher test positivity (22% for RTMCE vs 15% with non
      RTMCE, P = .0002). The increased test positivity occurred without a difference in
      positive predictive value in predicting >50% diameter stenoses by quantitative
      coronary angiography (67% for non-RTMCE, 73% for RTMCE). The mechanism for
      increased detection of CAD with RTMCE was mostly due to the detection of
      subendocardial wall thickening abnormalities that would have gone undetected when
      examining transmural wall thickening. CONCLUSIONS: RTMCE improves the detection
      of CAD during dobutamine and exercise stress echocardiography, mainly by the
      detection of subendocardial ischemia.

PMID- 22998857
TI  - [Urinary BLCA-4 level is useful to detect upper urinary tract urothelial cell
      carcinoma].
AB  - OBJECTIVE: Upper urinary tract urothelial cell carcinomas (UUT-UCCs) are rare but
      usually invasive at diagnosis. Early diagnosis of UUT-UCCs is thus warranted. UUT
      has the same embryological origin with bladder and BLCA-4 is a highly sensitive
      and specific marker for bladder cancer. We intend to investigate the viability of
      BLCA-4 in detecting UUT-UCCs. MATERIAL AND METHODS: Urines from 30 UUT-UCC
      patients, 10 ureteral polyp patients, 20 infected patients with incarcerated
      ureteral stones, and 30 normal controls were included. BLCA-4 antibody was
      produced and applied in an indirect ELISA assay. RESULTS: Urinary BLCA-4 is
      significantly higher in UUT-UCC group than "Polyp" group (P=0.0017), "Infection"
      group (P<0.0001), or " Normal" group (P<0.0001). The "Polyp" group is also higher
      than "Infection" group (P=0.015), or "Normal" group (P=0.0009). ROC curve
      revealed at cut-off of 5.5*10(-4)A, sensitivity was 93.3% and specificity was
      100%. When grouped as ureteral mass vs normal, same cut-off value yielded 93.3%
      sensitivity and 83.3% specificity. At 2.4*10(-4)A, sensitivity was 56.7% and
      specificity was 97.2%. CONCLUSIONS: Urinary BLCA-4 is also highly specific in UUT
      UCCs detection. For incidentally identified ureteral mass, BLCA-4 can be
      considered an auxiliary indicator besides biopsy.

PMID- 22998858
TI  - Sleep to upscale, sleep to downscale: balancing homeostasis and plasticity.
AB  - The synaptic homeostasis hypothesis of sleep proposes that slow wave sleep (SWS)
      causes downscaling of synaptic networks potentiated during information uptake in
      prior wakefulness. Two studies in Neuron challenge this mechanism. Chauvette et
      al. (2012) show that SWS mediates an up- rather than downregulation of excitatory
      postsynaptic potential responses. Grosmark et al. (2012) find that downscaling in
      hippocampal networks might be mediated through REM sleep theta rather than SWS.

PMID- 22998859
TI  - Neurodegeneration: new road leads back to the synapse.
AB  - Much of Parkinson's research over the last decade has focused on cellular stress
      as a candidate mechanism. In this issue of Neuron, a new study by Matta et al.
      (2012) addressing the biological functions of the Parkinson's gene LRRK2 now
      identifies a presynaptic substrate, homing in on the idea that synapse loss might
      be a central early aspect of neurodegeneration.

PMID- 22998860
TI  - Pten-less dentate granule cells make fits.
AB  - Hippocampal dentate granule cell abnormalities are thought to play a causative
      role in temporal lobe epilepsy, but their precise contribution has not been
      dissociated from coexisting pathological changes. In this issue of Neuron, Pun et
      al. (2012) show, for the first time, that inducing proexcitatory changes in a
      subset of DGCs in isolation is sufficient to cause epilepsy in a rodent.

PMID- 22998861
TI  - Asleep at the switch: MEK kinases control transit to gliogenesis in developing
      cortex.
AB  - In this issue of Neuron, Li et al. (2012) show that the neuron/glia cell fate
      switch of cortical progenitors is regulated by MEK1 and MEK2. The observations
      resonate with recent studies on the genesis of low-grade astrocytomas and
      highlight neuronal support functions of astrocytes in the postnatal brain.

PMID- 22998862
TI  - Choosing for me or choosing for you: value in medial prefrontal cortex.
AB  - In this issue of Neuron, Nicolle et al. (2012) suggest that choice-related value
      signals in ventromedial and anterior dorsomedial prefrontal cortex can be
      distinguished by their relevance to the current choice, as opposed to their
      reflection of preferences ascribed to the self versus another.

PMID- 22998863
TI  - Attending to the present when remembering the past.
AB  - In this issue of Neuron, Guerin et al. (2012) provide novel evidence that
      distinct parietal mechanisms for attention and memory compete when past
      experiences are compared to current perceptual input. While dorsal parietal
      cortex supports attention to perceptual stimuli, high attentional demands
      suppress ventral parietal regions important for veridical remembering.

PMID- 22998864
TI  - Implementing the 3Rs in neuroscience research: a reasoned approach.
AB  - The 3Rs--replacement, reduction, and refinement--are aimed at minimizing the
      welfare costs to animals used in research. Some neuroscientists fear that
      implementing the 3Rs will prohibit essential studies. Others view them as
      fundamental ethical principles that improve the quality of research. A regulatory
      system that integrates science and welfare is most likely to deliver public
      confidence.

PMID- 22998865
TI  - Plasticity of inhibition.
AB  - Until recently, the study of plasticity of neural circuits focused almost
      exclusively on potentiation and depression at excitatory synapses on principal
      cells. Other elements in the neural circuitry, such as inhibitory synapses on
      principal cells and the synapses recruiting interneurons, were assumed to be
      relatively inflexible, as befits a role of inhibition in maintaining stable
      levels and accurate timing of neuronal activity. It is now evident that
      inhibition is highly plastic, with multiple underlying cellular mechanisms. This
      Review considers these recent developments, focusing mainly on functional and
      structural changes in GABAergic inhibition of principal cells and long-term
      plasticity of glutamateric recruitment of inhibitory interneurons in the
      mammalian forebrain. A major challenge is to identify the adaptive roles of these
      different forms of plasticity, taking into account the roles of inhibition in the
      regulation of excitability, generation of population oscillations, and precise
      timing of neuronal firing.

PMID- 22998866
TI  - Neuronal dynamics and neuropsychiatric disorders: toward a translational paradigm
      for dysfunctional large-scale networks.
AB  - In recent years, numerous studies have tested the relevance of neural
      oscillations in neuropsychiatric conditions, highlighting the potential role of
      changes in temporal coordination as a pathophysiological mechanism in brain
      disorders. In the current review, we provide an update on this hypothesis because
      of the growing evidence that temporal coordination is essential for the context
      and goal-dependent, dynamic formation of large-scale cortical networks. We shall
      focus on issues that we consider particularly promising for a translational
      research program aimed at furthering our understanding of the origins of
      neuropsychiatric disorders and the development of effective therapies. We will
      focus on schizophrenia and autism spectrum disorders (ASDs) to highlight
      important issues and challenges for the implementation of such an approach.
      Specifically, we will argue that deficits in temporal coordination lead to a
      disruption of functional large-scale networks, which in turn can account for
      several specific dysfunctions associated with these disorders.

PMID- 22998867
TI  - Unreliable evoked responses in autism.
AB  - Autism has been described as a disorder of general neural processing, but the
      particular processing characteristics that might be abnormal in autism have
      mostly remained obscure. Here, we present evidence of one such characteristic:
      poor evoked response reliability. We compared cortical response amplitude and
      reliability (consistency across trials) in visual, auditory, and somatosensory
      cortices of high-functioning individuals with autism and controls. Mean response
      amplitudes were statistically indistinguishable across groups, yet trial-by-trial
      response reliability was significantly weaker in autism, yielding smaller signal
      to-noise ratios in all sensory systems. Response reliability differences were
      evident only in evoked cortical responses and not in ongoing resting-state
      activity. These findings reveal that abnormally unreliable cortical responses,
      even to elementary nonsocial sensory stimuli, may represent a fundamental
      physiological alteration of neural processing in autism. The results motivate a
      critical expansion of autism research to determine whether (and how) basic neural
      processing properties such as reliability, plasticity, and adaptation/habituation
      are altered in autism.

PMID- 22998868
TI  - Nanoscopy of living brain slices with low light levels.
AB  - Lens-based fluorescence microscopy, which has long been limited in resolution to
      about 200 nanometers by diffraction, is rapidly evolving into a nanoscale imaging
      technique. Here, we show that the superresolution fluorescence microscopy called
      RESOLFT enables comparatively fast and continuous imaging of sensitive, nanosized
      features in living brain tissue. Using low-intensity illumination to switch
      photochromic fluorescent proteins reversibly between a fluorescent and a
      nonfluorescent state, we increased the resolution more than 3-fold over that of
      confocal microscopy in all dimensions. Dendritic spines located 10-50 MUm deep
      inside living organotypic hippocampal brain slices were recorded for hours
      without signs of degradation. Using a fast-switching protein increased the
      imaging speed 50-fold over reported RESOLFT schemes, which in turn enabled the
      recording of spontaneous and stimulated changes of dendritic actin filaments and
      spine morphology occurring on time scales from seconds to hours.

PMID- 22998869
TI  - REM sleep reorganizes hippocampal excitability.
AB  - Sleep is composed of an alternating sequence of REM and non-REM episodes, but
      their respective roles are not known. We found that the overall firing rates of
      hippocampal CA1 neurons decreased across sleep concurrent with an increase in the
      recruitment of neuronal spiking to brief "ripple" episodes, resulting in a net
      increase in neural synchrony. Unexpectedly, within non-REM episodes, overall
      firing rates gradually increased together with a decrease in the recruitment of
      spiking to ripples. The rate increase within non-REM episodes was counteracted by
      a larger and more rapid decrease of discharge frequency within the interleaved
      REM episodes. Both the decrease in firing rates and the increase in synchrony
      during the course of sleep were correlated with the power of theta activity
      during REM episodes. These findings assign a prominent role of REM sleep in sleep
      related neuronal plasticity.

PMID- 22998870
TI  - LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis.
AB  - LRRK2 is a kinase mutated in Parkinson's disease, but how the protein affects
      synaptic function remains enigmatic. We identified LRRK2 as a critical regulator
      of EndophilinA. Using genetic and biochemical studies involving Lrrk loss-of
      function mutants and Parkinson-related LRRK2(G2019S) gain-of-kinase function, we
      show that LRRK2 affects synaptic endocytosis by phosphorylating EndoA at S75, a
      residue in the BAR domain. We show that LRRK2-mediated EndoA phosphorylation has
      profound effects on EndoA-dependent membrane tubulation and membrane association
      in vitro and in vivo and on synaptic vesicle endocytosis at Drosophila
      neuromuscular junctions in vivo. Our work uncovers a regulatory mechanism that
      indicates that reduced LRRK2 kinase activity facilitates EndoA membrane
      association, while increased kinase activity inhibits membrane association.
      Consequently, both too much and too little LRRK2-dependent EndoA phosphorylation
      impedes synaptic endocytosis, and we propose a model in which LRRK2 kinase
      activity is part of an EndoA phosphorylation cycle that facilitates efficient
      vesicle formation at synapses.

PMID- 22998871
TI  - Excessive activation of mTOR in postnatally generated granule cells is sufficient
      to cause epilepsy.
AB  - The dentate gyrus is hypothesized to function as a "gate," limiting the flow of
      excitation through the hippocampus. During epileptogenesis, adult-generated
      granule cells (DGCs) form aberrant neuronal connections with neighboring DGCs,
      disrupting the dentate gate. Hyperactivation of the mTOR signaling pathway is
      implicated in driving this aberrant circuit formation. While the presence of
      abnormal DGCs in epilepsy has been known for decades, direct evidence linking
      abnormal DGCs to seizures has been lacking. Here, we isolate the effects of
      abnormal DGCs using a transgenic mouse model to selectively delete PTEN from
      postnatally generated DGCs. PTEN deletion led to hyperactivation of the mTOR
      pathway, producing abnormal DGCs morphologically similar to those in epilepsy.
      Strikingly, animals in which PTEN was deleted from >= 9% of the DGC population
      developed spontaneous seizures in about 4 weeks, confirming that abnormal DGCs,
      which are present in both animals and humans with epilepsy, are capable of
      causing the disease.

PMID- 22998873
TI  - gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon
      guidance.
AB  - The Neurotrophic factor gdnf plays diverse developmental roles, supporting
      survival and also acting as a chemoattractant for axon and cell migration. We
      report that in the developing spinal cord, a focal source of gdnf is present in
      the floor plate (FP) where commissural axons cross the midline. Gdnf has no
      direct guidance properties but switches on the responsiveness of crossing
      commissural growth cones to the midline repellent Semaphorin3B by suppressing
      calpain-mediated processing of the Sema3B signaling coreceptor Plexin-A1.
      Analysis of single and double mutant mouse models indicates that although gdnf is
      the principal trigger of Sema3B midline repulsion, it acts with another FP cue,
      NrCAM. Finally, genetic and in vitro experiments provide evidence that this gdnf
      effect is RET independent and mediated by NCAM/GFRalpha1 signaling. This study
      identifies a regulator of midline crossing and reveals interplays between
      Semaphorin and gdnf signaling during axon guidance.

PMID- 22998872
TI  - MEK Is a Key Regulator of Gliogenesis in the Developing Brain.
AB  - We have defined functions of MEK in regulating gliogenesis in developing cerebral
      cortex using loss- and gain-of-function mouse genetics. Radial progenitors
      deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late
      embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In
      exploring mechanisms, we found that the key cytokine-regulated gliogenic pathway
      is attenuated. Further, the Ets transcription family member Etv5/Erm is strongly
      regulated by MEK and Erm overexpression can rescue the gliogenic potential of Mek
      deleted progenitors. Remarkably, Mek1/2-deleted mice surviving postnatally
      exhibit cortices almost devoid of astrocytes and oligodendroglia and exhibit
      neurodegeneration. Conversely, expression of constitutively active MEK1 leads to
      a major increase in numbers of astrocytes in the adult brain. We conclude that
      MEK is essential for acquisition of gliogenic competence by radial progenitors
      and that levels of MEK activity regulate gliogenesis in the developing cortex.

PMID- 22998874
TI  - Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control
      glutamate levels and neuronal excitability.
AB  - The paraneoplastic neurologic disorders target several families of neuron
      specific RNA binding proteins (RNABPs), revealing that there are unique aspects
      of gene expression regulation in the mammalian brain. Here, we used HITS-CLIP to
      determine robust binding sites targeted by the neuronal Elav-like (nElavl)
      RNABPs. Surprisingly, nElav protein binds preferentially to GU-rich sequences in
      vivo and in vitro, with secondary binding to AU-rich sequences. nElavl null mice
      were used to validate the consequence of these binding events in the brain,
      demonstrating that they bind intronic sequences in a position dependent manner to
      regulate alternative splicing and to 3'UTR sequences to regulate mRNA levels.
      These controls converge on the glutamate synthesis pathway in neurons; nElavl
      proteins are required to maintain neurotransmitter glutamate levels, and the lack
      of nElavl leads to spontaneous epileptic seizure activity. The genome-wide
      analysis of nElavl targets reveals that one function of neuron-specific RNABPs is
      to control excitation-inhibition balance in the brain.

PMID- 22998875
TI  - Transient sodium current at subthreshold voltages: activation by EPSP waveforms.
AB  - Tetrodotoxin (TTX)-sensitive sodium channels carry large transient currents
      during action potentials and also "persistent" sodium current, a noninactivating
      TTX-sensitive current present at subthreshold voltages. We examined gating of
      subthreshold sodium current in dissociated cerebellar Purkinje neurons and
      hippocampal CA1 neurons, studied at 37 degrees C with near-physiological ionic
      conditions. Unexpectedly, in both cell types small voltage steps at subthreshold
      voltages activated a substantial component of transient sodium current as well as
      persistent current. Subthreshold EPSP-like waveforms also activated a large
      component of transient sodium current, but IPSP-like waveforms engaged primarily
      persistent sodium current with only a small additional transient component.
      Activation of transient as well as persistent sodium current at subthreshold
      voltages produces amplification of EPSPs that is sensitive to the rate of
      depolarization and can help account for the dependence of spike threshold on
      depolarization rate, as previously observed in vivo.

PMID- 22998876
TI  - Metabolic communication between astrocytes and neurons via bicarbonate-responsive
      soluble adenylyl cyclase.
AB  - Astrocytes are proposed to participate in brain energy metabolism by supplying
      substrates to neurons from their glycogen stores and from glycolysis. However,
      the molecules involved in metabolic sensing and the molecular pathways
      responsible for metabolic coupling between different cell types in the brain are
      not fully understood. Here we show that a recently cloned bicarbonate (HCO3-)
      sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and
      becomes activated in response to HCO3- entry via the electrogenic NaHCO3
      cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing
      glycogen breakdown, enhanced glycolysis, and the release of lactate into the
      extracellular space, which is subsequently taken up by neurons for use as an
      energy substrate. This process is recruited over a broad physiological range of
      [K+](ext) and also during aglycemic episodes, helping to maintain synaptic
      function. These data reveal a molecular pathway in astrocytes that is responsible
      for brain metabolic coupling to neurons.

PMID- 22998878
TI  - An agent independent axis for executed and modeled choice in medial prefrontal
      cortex.
AB  - Adaptive success in social animals depends on an ability to infer the likely
      actions of others. Little is known about the neural computations that underlie
      this capacity. Here, we show that the brain models the values and choices of
      others even when these values are currently irrelevant. These modeled choices use
      the same computations that underlie our own choices, but are resolved in a
      distinct neighboring medial prefrontal brain region. Crucially, however, when
      subjects choose on behalf of a partner instead of themselves, these regions
      exchange their functional roles. Hence, regions that represented values of the
      subject's executed choices now represent the values of choices executed on behalf
      of the partner, and those that previously modeled the partner now model the
      subject. These data tie together neural computations underlying self-referential
      and social inference, and in so doing establish a new functional axis
      characterizing the medial wall of prefrontal cortex.

PMID- 22998877
TI  - Sleep oscillations in the thalamocortical system induce long-term neuronal
      plasticity.
AB  - Long-term plasticity contributes to memory formation and sleep plays a critical
      role in memory consolidation. However, it is unclear whether sleep slow
      oscillation by itself induces long-term plasticity that contributes to memory
      retention. Using in vivo prethalamic electrical stimulation at 1 Hz, which itself
      does not induce immediate potentiation of evoked responses, we investigated how
      the cortical evoked response was modulated by different states of vigilance. We
      found that somatosensory evoked potentials during wake were enhanced after a slow
      wave sleep episode (with or without stimulation during sleep) as compared to a
      previous wake episode. In vitro, we determined that this enhancement has a
      postsynaptic mechanism that is calcium dependent, requires hyperpolarization
      periods (slow waves), and requires a coactivation of both AMPA and NMDA
      receptors. Our results suggest that long-term potentiation occurs during slow
      wave sleep, supporting its contribution to memory.

PMID- 22998879
TI  - Interactions between visual attention and episodic retrieval: dissociable
      contributions of parietal regions during gist-based false recognition.
AB  - The interaction between episodic retrieval and visual attention is relatively
      unexplored. Given that systems mediating attention and episodic memory appear to
      be segregated, and perhaps even in competition, it is unclear how visual
      attention is recruited during episodic retrieval. We investigated the recruitment
      of visual attention during the suppression of gist-based false recognition, the
      tendency to falsely recognize items that are similar to previously encountered
      items. Recruitment of visual attention was associated with activity in the dorsal
      attention network. The inferior parietal lobule, often implicated in episodic
      retrieval, tracked veridical retrieval of perceptual detail and showed reduced
      activity during the engagement of visual attention, consistent with a competitive
      relationship with the dorsal attention network. These findings suggest that the
      contribution of the parietal cortex to interactions between visual attention and
      episodic retrieval entails distinct systems that contribute to different
      components of the task while also suppressing each other.

PMID- 22998880
TI  - Total antioxidant capacity from diet and risk of myocardial infarction: a
      prospective cohort of women.
AB  - BACKGROUND: There are no previous studies investigating the effect of all dietary
      antioxidants in relation to myocardial infarction. The total antioxidant capacity
      of diet takes into account all antioxidants and synergistic effects between them.
      The aim of this study was to examine how total antioxidant capacity of diet and
      antioxidant-containing foods were associated with incident myocardial infarction
      among middle-aged and elderly women. METHODS: In the population-based prospective
      Swedish Mammography Cohort of 49-83-year-old women, 32,561 were cardiovascular
      disease-free at baseline. Women completed a food-frequency questionnaire, and
      dietary total antioxidant capacity was calculated using oxygen radical absorbance
      capacity values. Information on myocardial infarction was identified from the
      Swedish Hospital Discharge and the Cause of Death registries. Hazard ratios (HR)
      and 95% confidence intervals (CI) were calculated using Cox proportional hazard
      models. RESULTS: During the follow-up (September 1997-December 2007), we
      identified 1114 incident cases of myocardial infarction (321,434 person-years).
      In multivariable-adjusted analysis, the HR for women comparing the highest
      quintile of dietary total antioxidant capacity to the lowest was 0.80 (95% CI,
      0.67-0.97; P for trend=0.02). Servings of fruit and vegetables and whole grains
      were nonsignificantly inversely associated with myocardial infarction.
      CONCLUSIONS: These data suggest that dietary total antioxidant capacity, based on
      fruits, vegetables, coffee, and whole grains, is of importance in the prevention
      of myocardial infarction.

PMID- 22998881
TI  - Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating
      agents: a MRI study.
AB  - BACKGROUND: Most dialysis patients receiving erythropoesis-stimulating agents
      (ESA) also receive parenteral iron supplementation. There are few data on the
      risk of hemosiderosis in this setting. METHODS: We prospectively measured liver
      iron concentration by means of T1 and T2* contrast magnetic resonance imaging
      (MRI) without gadolinium, in a cohort of 119 fit hemodialysis patients receiving
      both parenteral iron and ESA, in keeping with current guidelines. RESULTS: Mild
      to severe hepatic iron overload was observed in 100 patients (84%; confidence
      interval, [CI] 76%-90%), of whom 36% (CI, 27%-46%) had severe hepatic iron
      overload (liver iron concentration >201 MUmol/g of dry weight). In the cross
      sectional study, infused iron, hepcidin, and C-reactive protein values correlated
      with hepatic iron stores in both univariate analysis (P<.05, Spearman test) and
      binary logistic regression (P <.05). In 11 patients who were monitored closely
      during parenteral iron therapy, the iron dose infused per month correlated
      strongly with both the overall increase and the monthly increase in liver iron
      concentration (respectively, rho=0.66, P=.0306 and rho=0.85, P=0.0015, Spearman
      test). In the 33 patients with iron overload, iron stores fell significantly
      after iron withdrawal or after a major reduction in the iron dose (first MRI: 220
      MUmol/g (range: 60-340); last MRI: 50 MUmol/g (range: 5-210); P <.0001,
      Wilcoxon's paired test). CONCLUSIONS: Most hemodialysis patients receiving ESA
      and intravenous iron supplementation have hepatic iron overload on MRI. These
      findings call for a revision of guidelines on iron therapy in this setting,
      especially regarding the amount of iron infused and noninvasive methods for
      monitoring iron stores.

PMID- 22998882
TI  - Interactive journals and the future of medical publications.

PMID- 22998883
TI  - Damage and duty hours? A proposal for further study.

PMID- 22998884
TI  - Test appropriateness index.

PMID- 22998886
TI  - Ghostwriting: an existing problem.

PMID- 22998888
TI  - Don't be a fool--don't use fool's gold.

PMID- 22998890
TI  - Confounding factors for the compilation of the risk score.

PMID- 22998891
TI  - Patterns of medication initiation in newly diagnosed diabetes mellitus: quality
      and cost implications.
AB  - Currently, 25 million Americans are known to have diabetes, with an additional 7
      million cases believed to be undiagnosed. It is estimated that direct and
      indirect costs of diabetes top $200 billion. Due to the significant health and
      financial burdens associated with diabetes, it is imperative that this disease be
      treated quickly and aggressively. In 2009, the American Diabetes Association and
      the European Association for the Study of Diabetes developed a consensus
      statement regarding the treatment of type 2 diabetes, citing lifestyle
      modification and metformin as the preferred first line therapies. In this study,
      the authors looked at prescription claims data for adults who were newly
      initiated on oral hypoglycemic monotherapy between January 1, 2006, and December
      31, 2008, to determine if initiation patterns changed over time, to evaluate how
      well the treatment guidelines were being followed, and to assess the economic
      consequences of prescribing patterns by drug class for both patients and
      insurers. The results showed that over the course of the study period the
      proportion of patients initially treated with metformin increased, whereas those
      receiving sulfonylureas as first-line therapy decreased. Thiazolidinediones
      experienced the greatest decrease, falling from 20% to 8%, while prescriptions
      for dipeptidyl peptidase-4 inhibitors increase from 0-7%. Over a 6-month period,
      patients taking metformin or sulfonylureas paid approximately $38 to $40 in co
      pays while insurance paid about $77. Patients taking other agents paid
      approximately $130 in co-pays and insurance paid over $500. The authors concluded
      that based its cost and safety profile, metformin should be the first line drug
      therapy for patients with newly diagnosed type 2 diabetes. This CME multimedia
      activity, which is part of a 2-part multimedia activity on the management and
      treatment of diabetes, contains a video presentation and is available through the
      website of The American Journal of Medicine at
      http://amjmed.com/content/multimedia. Click on "Patterns of Medication Initiation
      in Newly Diagnosed Diabetes Mellitus: Quality and Cost Implications" to access
      this part of the multimedia program.

PMID- 22998892
TI  - Management of type 2 diabetes: new and future developments in treatment.
AB  - To date, six classes of oral medication have been approved by the U.S. Food and
      Drug Administration for the treatment of type 2 diabetes and several new agents
      are in the pipeline. In 2009, the American Diabetes Association and the European
      Association for the Study of Diabetes developed a consensus statement regarding
      the treatment of type 2 diabetes, citing lifestyle modification and metformin as
      the preferred first line therapies. In addition to the currently available drugs,
      several new agents have recently been introduced or are in the development
      pipeline. Incretin therapies include both glucagon-like peptide-1 (GLP-1)
      inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. Non-incretin beta cell
      stimulants still in development include glucokinase activators, G-protein-coupled
      receptors, and anti-inflammatory and anti-oxidant therapies. Additional agents
      that target glucose synthesis include glucose-6-phosphatase and glycogen
      phosphorylase. Other new agents target metabolic syndrome, which is often the
      first clinical condition that presents in patients at risk for type 2 diabetes.
      Finally, for obese patients who are unable to lose weight through diet and
      exercise, weight-loss surgery is an option that should be discussed with their
      physicians. This CME multimedia activity, which is part of a 2-part multimedia
      activity on the management and treatment of diabetes, contains a video
      presentation and is available through the website of The American Journal of
      Medicine at http://amjmed.com/content/multimedia. Click on "Management of Type 2
      Diabetes: New and Future Developments in Treatment" to access this part of this
      multimedia program.

PMID- 22998893
TI  - Fibre orientation of fresh and frozen porcine aorta determined non-invasively
      using diffusion tensor imaging.
AB  - Diffusion tensor imaging analysis was applied to fresh and frozen porcine aortas
      in order to determine fibre orientation. Fresh and stored frozen porcine aortas
      were imaged in a 7 T scanner with a diffusion weighted spin echo sequence (six
      gradient directions, matrix 128*128 pixels, 2.8 cm*2.8 cm field of view). The
      images were taken for different b values, ranging from 200 s/mm(2) to 1600
      s/mm(2). For each dataset the diffusion tensor was evaluated, fractional
      anisotropy (FA) maps were calculated, and the fibres mapped. The arterial fibres
      resulting were postprocessed and their fibre angle evaluated. The FA maps, the
      dominant fibre angle, and the fibre pattern in the arterial wall thickness were
      compared in the fresh and in the stored frozen aortas. The technique was able to
      determine a fibre pattern in the fresh healthy aorta that is in accordance with
      the data available in literature and to identify an alteration in the fibre
      pattern caused by freezing. This study shows that this technique has potential
      for studying fibre orientation and fibre distribution in humans and could be
      further developed to diagnose fibre alterations due to cardiovascular diseases.
      In fact, our results suggest that DTI has the potential to determine the fibrous
      structure of arteries non-invasively. This capability could be further developed
      to study the natural remodelling of the aorta in vivo due to age and/or gender or
      to obtain information on aortic diseases at an early stage of their evolution.

PMID- 22998894
TI  - Contractions, a risk for premature rupture of fetal membranes: a new protocol
      with cyclic biaxial tension.
AB  - This study aims at investigating the effect of repeated mechanical loading on the
      rupture and deformation properties of fetal membranes. Ten membranes delivered by
      cesarean sections were tested using a custom-built inflation device which
      provides a multi-axial stress state. For each membrane, a group of samples was
      first cyclically stretched by application of pressure ranging between 10 and 40
      mmHg. After cycles, samples were subjected to inflation up to rupture.
      Differences between mechanical parameters from cycled and uncycled samples were
      analyzed. Ten cycles at 40% of mean critical membrane tension--representative of
      mean physiologic contractions--did not affect strength and stiffness of fetal
      membranes but reduced the work to rupture, thus indicating that contractions
      might increase the risk of premature rupture of the membrane. Cyclic testing
      demonstrated a large hysteresis loop and irreversible deformation on the first
      cycle, followed by rapid stabilization on subsequent cycles. In 80% of tests,
      amnion ruptured first and at the periphery of the sample, under uniaxial strain
      state. Chorion ruptured at higher deformation levels in the middle, under biaxial
      strain state.

PMID- 22998895
TI  - Suitability of DCPs with screw locking elements to allow sufficient
      interfragmentary motion to promote secondary bone healing of osteoporotic
      fractures.
AB  - This paper analyses the suitability of a system comprising a Dynamic Compression
      Plate (DCP) and Screw Locking Elements (SLEs) to allow sufficient
      interfragmentary motion to promote secondary bone healing in osteoporotic
      fractures. Four fixation systems were mounted on bone-simulating reinforced epoxy
      bars filled with solid rigid polyurethane foam. Group 1, used for comparison
      purposes, represents a system comprised of a Locking Compression Plate (LCP) and
      eight locking screws. Groups 2 and 3 represent a system comprised of a DCP plate
      with eight cortical screws and two SLEs placed on the screws furthest from (group
      2) and nearest to (group 3) the fracture. Group 4 represents the system comprised
      of a DCP plate with SLEs placed on all eight cortical screws. Cyclic compression
      tests of up to 10,000 load cycles were performed in order to determine the
      parameters of interest, namely the stiffnesses and the interfragmentary motion of
      the various configurations under consideration. Tukey's multiple comparison test
      was used to analyse the existence or otherwise of significant differences between
      the means of the groups. At 10,000 cycles, interfragmentary motion at the far
      cortex for group 2 was 0.60+/-0.04 mm and for group 3 0.59+/-0.03 mm (there being
      no significant differences: p=0.995). The mean interfragmentary motion at the far
      cortex of the LCP construct was 70% less than that of the two groups with 2SLEs
      (there being significant differences: p=1.1*10(-8)). In the case of group 4 this
      figure was 45% less than in groups 2 and 3 (there being significant differences:
      p=5.6*10(-6)). At 10,000 cycles, interfragmentary motion at the near cortex for
      group 2 was 0.24+/-0.06 mm and for group 3 0.24+/-0.03 mm (there being no
      significant differences: p=1.000). The mean interfragmentary motion at the near
      cortex of the LCP construct was 70.8% less than that of the two groups with 2SLEs
      (there being significant differences: p=0.011). In the case of group 4 this
      figure was 66.7% less than in groups 2 and 3 (there being significant
      differences: p=0.016). The mean stiffness at 10,000 cycles was 960+/-110 N mm(-1)
      for group 2 and 969+/-53 N mm(-1) for group 3 (there being no significant
      differences: p=1.000). For group 1 (the LCP construct) the mean stiffness at
      10,000 cycles was 3144+/-446 N mm(-1), 3.25 times higher than that of groups 2
      and 3 (there being significant differences: p=0.00002), and 1.6 times higher than
      that of the DCP+8SLEs construct (1944+/-408 N mm(-1), there being significant
      differences: p=0.007). It is concluded that using the DCP+2SLEs construct
      sufficient interfragmentary motion is ensured to promote secondary bone healing.
      However, if too many SLEs are used the result may be, as with the LCP, an
      excessively rigid system for callus formation.

PMID- 22998896
TI  - Concept and evaluation of an endaurally insertable middle-ear implant.
AB  - A concept for a partially implantable hearing device, for which the power supply
      and signal transmission are provided by an optical transmission path, is
      evaluated. The actuator is designed to fit into the round-window niche and to
      couple directly to the round-window membrane. Implantable hearing aids can be a
      suitable solution in the case of severe hearing loss, where conventional hearing
      aids often fail. However, the surgical effort for an implantation is
      comparatively high. Therefore, the objective of our work was to provide a hearing
      system which combines reliable coupling to the auditory system with an easy
      implantation technique. The actuator was designed as a piezoelectric thin-film
      cantilever. The optical transmission path was realised using an infrared light
      emitting diode combined with an active receiver circuit. For a voltage of 1V, the
      unloaded actuator presents displacement amplitudes of 1MUm up to a stimulus
      frequency of 25kHz and forces up to 0.2mN. Proportionally larger forces can be
      achieved by stacking single actuators. The overall transmission loss from the
      electrical input of the light-emitting diode driver to the mechanical output of
      the unloaded actuator was less than 25dB at 1kHz and maximum output.

PMID- 22998897
TI  - Mesenchymal stem cells combined with an artificial dermal substitute improve
      repair in full-thickness skin wounds.
AB  - Autografts represent the gold standard for the treatment of full thickness burns.
      Factors such as lack of suitable donor sites and poor skin quality, however, have
      led to the development of artificial dermal substitutes. The investigation of
      mechanisms leading to enhanced functionality of these skin substitutes has been
      attracting great attention. This study aimed to investigate the effect of
      autologous stem cells on the integration and vascularization of a dermal
      substitute in full-thickness skin wounds, in a murine model. Two cell populations
      were compared, whole bone marrow cells and cultivated mesenchymal stem cells,
      isolated from mice transgenic for the enhanced green fluorescent protein, which
      allowed tracking of the transplanted cells. The number of cells colonizing the
      dermal substitute, as well as vascular density, were higher in mice receiving
      total bone marrow and particularly mesenchymal stem cells, than in control
      animals. The effect was more pronounced in animals treated with mesenchymal stem
      cells, which located primarily in the wound bed, suggesting a paracrine
      therapeutic mechanism. These results indicate that combining mesenchymal stem
      cells with artificial dermal substitutes may represent an important potential
      modality for treating full thickness burns, even in allogeneic combinations due
      to the immunoregulatory property of these cells.

PMID- 22998898
TI  - Minimally invasive surgery in infants. Con.

PMID- 22998899
TI  - Economic burden of repeat renal surgery on solitary kidney--do the ends justify
      the means? A cost analysis.
AB  - PURPOSE: Despite the high morbidity of repeat renal surgery in patients with
      multifocal recurrent renal carcinoma, in most patients adequate renal function is
      preserved to obviate the need for dialysis. To our knowledge the economic burden
      of repeat renal surgery has not been evaluated. We provide a cost analysis for
      patients requiring repeat renal surgery on a solitary kidney. MATERIALS AND
      METHODS: We reviewed the charts of patients treated at the National Cancer
      Institute who required repeat renal surgery from 1989 to 2010. Functional,
      oncological and surgical outcomes were evaluated and the costs of repeat renal
      surgery were calculated. We then compared costs in a cohort of 33 patients who
      underwent repeat renal surgery on a solitary kidney and in a hypothetical patient
      cohort treated with uncomplicated nephrectomy, fistula placement and dialysis.
      All costs were calculated based on Medicare reimbursement rates derived from CPT
      codes. Cost analysis was performed. RESULTS: Despite a high 45% complication
      rate, 87% of patients maintained renal function that was adequate to avoid
      dialysis and 96% remained metastasis free at an average followup of 3.12 years
      (range 0.3 to 16.4). Compared to the hypothetical dialysis cohort, the financial
      benefit of repeat renal surgery was reached at 0.68 years. CONCLUSIONS: Repeat
      renal surgery is a viable alternative for patients with multifocal renal cell
      carcinoma requiring multiple surgical interventions, especially when left with a
      solitary kidney. Despite the high complication rate, renal function is preserved
      in most patients and they have an excellent oncological outcome. The financial
      benefit of repeat renal surgery is reached at less than 1 year.

PMID- 22998900
TI  - Genetics of erectile dysfunction.
AB  - PURPOSE: Erectile dysfunction affects 50% of men older than 40 years. Recently
      more attempts have been made to identify genetic predictors of this disease. We
      reviewed animal and human data on genes related to the development and increased
      risk of erectile dysfunction. MATERIALS AND METHODS: A literature search was
      performed using the PubMed(r) database. Articles addressing genes involved in
      erectile dysfunction were evaluated. RESULTS: The majority of studies used a
      candidate gene approach to investigate genetic polymorphisms of known pathways
      mediating erection/detumescence. Studies in human and animal models are
      available. Human studies often compared the frequency of a specifically
      predetermined genetic polymorphism in men with erectile dysfunction to that in
      matched controls in whom few genes were persistently replicated. Several gene
      expression profiling studies are available that targeted specific erectile
      dysfunction models. Currently, there are few human genome wide association
      studies of erectile dysfunction. CONCLUSIONS: Studies investigating the genetics
      of erectile dysfunction are mostly derived from animal models and candidate gene
      approaches. Candidate gene studies omit the greater portion of the genome, a
      problem that can be solved using a genome wide association study approach. The
      lack of persistently replicated results of candidate gene studies may be related
      to different patient ethnic backgrounds, variations in erectile dysfunction
      etiology and small sample sizes. Using strict inclusion/exclusion criteria for
      erectile dysfunction etiology and ethnicity in human studies may lead to improved
      understanding of the genetics of erectile dysfunction in specific populations.

PMID- 22998901
TI  - Diagnostic performance of PCA3 to detect prostate cancer in men with increased
      prostate specific antigen: a prospective study of 1,962 cases.
AB  - PURPOSE: The detection of prostate cancer relies primarily on abnormal digital
      rectal examination or increased serum prostate specific antigen concentration.
      However, low positive predictive values result in many men with increased
      prostate specific antigen and/or suspicious digital rectal examination having a
      negative biopsy. We investigated the value of the PCA3 (prostate cancer gene 3)
      urine test in predicting the likelihood of diagnosis of cancer before biopsy.
      MATERIALS AND METHODS: We performed a prospective, community based clinical trial
      to evaluate PCA3 score before any biopsy. This trial was conducted at 50 urology
      practices in the United States. Samples were obtained from 1,962 men with
      increased serum prostate specific antigen (greater than 2.5 ng/ml) and/or
      abnormal digital rectal examination before transrectal prostate needle biopsy.
      Study samples (urinary PCA3 and biopsies) were processed and analyzed by a
      central laboratory. Sensitivity-specificity analyses were conducted. RESULTS: A
      total of 1,913 urine samples (97.5%) were adequate for PCA3 testing. Of 802 cases
      diagnosed with prostate cancer 222 had high grade prostatic intraepithelial
      neoplasia or atypical small acinar proliferation and were suspicious for cancer,
      whereas 889 cases were benign. The traditional PCA3 cutoff of 35 reduced the
      number of false-positives from 1,089 to 249, a 77.1% reduction. However, false
      negatives (missed cancers) increased significantly from 17 to 413, an increase of
      more than 2,300%. Lowering the PCA3 cutoff to 10 reduced the number of false
      positives 35.4% and false-negatives only increased 5.6%. CONCLUSIONS: Urinary
      PCA3 testing in conjunction with prostate specific antigen has the potential to
      significantly decrease the number of unnecessary prostate biopsies.

PMID- 22998902
TI  - Association of tumor size, location, R.E.N.A.L., PADUA and centrality index score
      with perioperative outcomes and postoperative renal function.
AB  - PURPOSE: Multiple scoring systems have been proposed to standardize the
      description of anatomical features of renal tumors. However, it remains unclear
      which of these systems, if any, is most useful, or whether any performs better
      than simply reporting tumor size or location in patients undergoing partial
      nephrectomy. To clarify these issues we evaluated the association of tumor size,
      location, R.E.N.A.L. (Radius/Exophytic/Nearness to collecting
      system/Anterior/Location), PADUA (Preoperative Aspects and Dimensions Used for an
      Anatomical classification) and centrality index scores with perioperative
      outcomes. MATERIALS AND METHODS: Patients undergoing partial nephrectomy with
      available preoperative imaging were identified from 2005 to 2011. R.E.N.A.L.,
      PADUA and centrality index scores were assigned according to the described
      protocols for those systems. Associations between each variable and ischemia
      time, estimated blood loss, total operative time and change in estimated
      glomerular filtration rate were examined. RESULTS: A total of 162 patients were
      identified with a median tumor size of 3.1 cm (IQR 2.2 to 4.6). Median estimated
      blood loss, ischemia time and total operative time were 200 ml (IQR 100 to 300),
      24 minutes (IQR 20 to 30) and 211 minutes (IQR 179 to 249), respectively. Each
      scoring system was found to have a statistically significant (p <0.001)
      correlation with ischemia time, with the centrality index system showing the
      strongest correlation. Furthermore, each of the scoring systems showed a stronger
      correlation with ischemia time than tumor size or tumor location. CONCLUSIONS:
      Each scoring system outperformed tumor size and location, and may be useful when
      describing the surgical complexity of renal tumors treated with partial
      nephrectomy.

PMID- 22998903
TI  - The impact of neuropathic pain in the chronic pelvic pain population.
AB  - PURPOSE: Patients with chronic pelvic pain disorders often present with
      neuropathic features. We examined a cohort of patients with a primary complaint
      of chronic pelvic pain for the presence of neuropathic pain symptoms. MATERIALS
      AND METHODS: Patients with chronic pelvic pain disorders from 2 tertiary referral
      centers were prospectively evaluated. The validated S-LANSS (Self-Administered
      Leeds Assessment of Neuropathic Symptoms and Signs) survey was used to examine
      pain symptoms of neuropathic origin. Patients completed SF-12v2TM to assess
      mental/physical health domains. The 2-tailed t test and chi-square analysis were
      used to compare physical and mental component summaries in patients with vs
      without neuropathic symptoms. RESULTS: A total of 142 patients mean age of 45
      years were included in analysis. Of the patients 72.5% with chronic pelvic pain
      carried more than 1 primary diagnosis. The S-LANSS survey identified symptoms
      suggestive of neuropathic pain in 44 patients (31%). A greater proportion of
      patients with a neuropathic component had altered sensation in the affected area
      (86.4% vs 24.5%). Patients with neuropathic pain scored 4.28 and 5.45 points
      lower on the physical and mental component summaries (p = 0.053 and 0.008,
      respectively). CONCLUSIONS: A large proportion of patients with chronic pelvic
      pain present with neuropathic features and report decreased quality of life
      compared with the general population. Those with neuropathic symptoms have
      significantly lower quality of life than those without such symptoms. Clinicians
      can identify patients to use targeted therapies and use a multidisciplinary
      approach to care.

PMID- 22998904
TI  - Stepwise description and outcomes of bladder neck sparing during robot-assisted
      laparoscopic radical prostatectomy.
AB  - PURPOSE: While bladder neck sparing may improve post-prostatectomy urinary
      continence, there is concern that it may lead to more positive surgical margins
      and compromise cancer control. We compared the continence and cancer control
      outcomes of bladder neck sparing vs nonsparing techniques during robot-assisted
      laparoscopic radical prostatectomy. MATERIALS AND METHODS: Data were
      prospectively collected on 1,067 robot-assisted laparoscopic radical
      prostatectomies done from September 2005 through October 2011. We compared the
      procedures according to bladder neck sparing (791) and nonsparing (276).
      Continence was defined by zero pad responses on the EPIC (Expanded Prostate
      Cancer Index) item quantifying daily use. Biochemical recurrence was defined as
      prostate specific antigen 0.1 ng/ml or greater. Cox regression was performed to
      assess factors associated with post-prostatectomy continence and biochemical
      recurrence-free survival. RESULTS: Median followup for bladder neck sparing vs
      nonsparing was 25.8 vs 51.7 months. Men treated with bladder neck sparing were
      more likely to have clinical T1c tumors (p <0.001) and less likely to have biopsy
      Gleason grade 6 or less disease (p = 0.023). They experienced fewer urinary leaks
      (p = 0.009) and shorter length of stay (p = 0.006). Regarding cancer control
      outcomes, there was no difference in bladder neck sparing vs nonsparing base
      (1.2% vs 2.6%, p = 0.146) and overall surgical margin positivity (each 13.8%, p =
      0.985). On adjusted analyses bladder neck sparing vs nonsparing was associated
      with better continence (HR 1.69, 95% CI 1.43-1.99) and similar biochemical
      recurrence-free survival (HR 1.20, 95% CI 0.62-2.31, p = 0.596). CONCLUSIONS:
      Bladder neck sparing is associated with fewer urinary leak complications, shorter
      hospitalization and better post-prostatectomy continence without compromising
      cancer control compared to bladder neck nonsparing.

PMID- 22998905
TI  - Biomarker discovery in penile cancer.

PMID- 22998906
TI  - Can we predict the outcome of 532 nm laser photoselective vaporization of the
      prostate? Time to event analysis.
AB  - PURPOSE: We evaluated the safety, efficacy and predictability of the long-term
      outcome of GreenLightTM (532 nm laser) photoselective vaporization of the
      prostate to treat patients with lower urinary tract symptoms secondary to benign
      prostatic hyperplasia. MATERIALS AND METHODS: We performed a longitudinal study
      of patients who underwent GreenLight (532 nm laser) photoselective vaporization
      of the prostate at our center between June 2002 and November 2011. All patient
      data were prospectively maintained in the prostate unit database. Two types of
      laser equipment were used, including the KTP in 91 cases (31.6%) and the
      GreenLight HPSTM in 197 (68.4%). RESULTS: Larger glands were treated with HPS and
      KTP photoselective vaporization (mean +/- SD volume 45.6 +/- 22.5 and 39.6 +/-
      15.2 ml, respectively, p <0.05). After photoselective vaporization with the KTP
      laser, we noted a 59.1% and 61.8% decrease in the International Prostate Symptom
      Score, and a 140.7% and 118.4% improvement in the maximal urine flow rate at 1
      and 5 years, respectively. Similarly, after prostate vaporization with the HPS we
      observed a 65.1% and 62.1% decrease in the International Prostate Symptom Score,
      and a 123.1% and 107.3% improvement in the maximal urine flow rate at 1 and 4
      years, respectively. At a mean of 40.5 months (range 3 to 114) of followup
      reoperation was indicated in 7.6% of cases. The overall rates of bladder neck
      contracture, de novo urethral stricture and residual/recurrent adenoma were 3.4%
      (10 cases), 2.1% (6) and 2.1% (6) with no statistically significant difference
      between vaporization with the KTP and HPS lasers. Most adverse events occurred
      during year 1 postoperatively. More bladder neck contractures developed after
      vaporization was done in smaller glands (p <0.05). More cases with residual
      prostatic adenoma had a prostate volume of 50 ml or greater vs less than 50 ml (4
      of 71 or 5.6% vs 2 of 207 or 0.96%). CONCLUSIONS: GreenLight (532 nm laser)
      photoselective vaporization of the prostate seems to be safe and effective for
      lower urinary tract symptoms secondary to benign prostatic hyperplasia. A long
      lasting, successful outcome is predictable. With careful surveillance during year
      1 postoperatively and early intervention for adverse events, a sustainable
      functional outcome could be achieved without re-treatment.

PMID- 22998907
TI  - A phase II study of oportuzumab monatox: an immunotoxin therapy for patients with
      noninvasive urothelial carcinoma in situ previously treated with bacillus
      Calmette-Guerin.
AB  - PURPOSE: A phase II study was performed to assess the efficacy and tolerability
      of intravesical oportuzumab monatox in patients with urothelial carcinoma in situ
      of the bladder. Bacillus Calmette-Guerin treatment had previously failed in all
      patients. MATERIALS AND METHODS: A total of 46 patients received 1 induction
      cycle of 6 (cohort 1) or 12 (cohort 2) weekly intravesical oportuzumab monatox
      (VB4-845) instillations of 30 mg, followed by up to 3 maintenance cycles of 3
      weekly administrations every 3 months. RESULTS: A complete response to
      oportuzumab monatox was seen in 9 of 22 patients (41%) in cohort 1 and 9 of 23
      (39%) in cohort 2 at the 3-month evaluation. A total of 20 patients (44%)
      achieved a complete response. Two other patients without carcinoma in situ who
      achieved a complete response were not included in the study due to the
      development of noninvasive papillary (Ta) disease. Median time to recurrence in
      patients who achieved a complete response was 274 and 408 days in cohorts 1 and
      2, respectively. Overall 7 patients (16%) remained disease-free. Post-study
      assessment demonstrated that these patients were still disease-free at last
      followup (18 to 25 months). The most common adverse events were mild to moderate
      reversible bladder symptoms. CONCLUSIONS: Oportuzumab monatox was effective and
      well tolerated in patients with bacillus Calmette-Guerin refractory carcinoma in
      situ of the bladder. These results demonstrate the clinical benefit of
      oportuzumab monatox and support its continued development for the second line
      treatment of nonmuscle invasive bladder cancer.

PMID- 22998908
TI  - Joint effect of arsenic methylation profile and NNK metabolites on urothelial
      carcinoma.
AB  - PURPOSE: Cigarette smoking interacts with the urinary arsenic profile to modify
      the risk of urothelial carcinoma. NNK (4-[methylnitrosamino]-1-[3-pyridyl]-1
      butanone) and its metabolite NNAL (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol)
      are biomarkers for cigarette smoking exposure. We explored the joint effects of
      urinary NNK metabolites and arsenic species on urothelial carcinoma risk.
      MATERIALS AND METHODS: We recruited 137 pairs of urothelial carcinoma cases and
      matched healthy participants for a hospital based case-control study.
      Participants completed questionnaires and provided 50 ml urine samples. Urine
      samples were analyzed for free NNAL and NNAL-glucuronides using liquid
      chromatography-tandem mass spectrometry. Samples were analyzed for arsenic
      species using high performance liquid chromatography hydride generator atomic
      absorption spectrometry. RESULTS: Overall, subjects with high urinary total NNAL
      and high total arsenic had a greater urothelial carcinoma risk than those with a
      low total NNAL and low total arsenic. Subjects with a lower ratio of NNAL
      glucuronides-to-free NNAL and higher total arsenic had a greater urothelial
      carcinoma risk than those with a higher NNAL-glucuronides-to-free NNAL ratio and
      lower total arsenic. CONCLUSIONS: This is the first study to our knowledge to
      demonstrate a significant trend of progressively increased risk of urothelial
      carcinoma in subjects who had none, one or both of the factors of urinary total
      arsenic and total NNAL or urinary total arsenic and the ratio of NNAL
      glucuronides-to-free NNAL.

PMID- 22998909
TI  - Pelvic floor structure and function in women with vesicovaginal fistula.
AB  - PURPOSE: Vesicovaginal fistula is a catastrophic event, especially in areas with
      poor peripartum care, where most occur. It is usually due to severely obstructed
      and protracted labor. We assumed that such patients would show evidence of
      abnormal levator function, eg due to denervation. MATERIALS AND METHODS: In an
      external audit at Hamlin Fistula Hospital in Addis Ababa, Ethiopia, 95 women were
      seen for clinical examination and 4-dimensional translabial ultrasound. Patients
      were examined supine and after voiding. Volume data sets were obtained upon
      coughing, Valsalva maneuver and pelvic floor muscle contraction. RESULTS: Women
      were seen before (22) or after (73) vesicovaginal fistula repair. Mean age was
      29.5 years (range 16 to 65) and mean parity was 2.7 (range 1 to 11). Only 2
      patients had a significant cystocele (stage 2), 3 had stage 2 uterine prolapse
      and 13 had a stage 2 rectocele. Levator biometry was done in 92 of 95 women,
      which showed no evidence of muscle atrophy. Mean hiatal area on Valsalva was 18.8
      cm(2) (range 7.7 to 45.9) and only 6 of the 92 women (7%) fulfilled the criteria
      for ballooning (hiatal distention 25 cm(2) or greater). Levator avulsion was
      diagnosed in 27 cases (28%), of which 11 were bilateral. Reflex contraction of
      the levator ani was observed upon coughing in all except 2 patients. Levator
      contraction upon request could be performed by all except 6 women. CONCLUSIONS:
      Abnormal levator function and anatomy in patients with vesicovaginal fistula is
      not uncommon but no more than in unselected urogynecologic patients in the
      developed world. There was no evidence of permanent denervation of the levator
      ani.

PMID- 22998910
TI  - Can renal biopsy accurately predict histological subtype and Fuhrman grade of
      renal cell carcinoma?
AB  - PURPOSE: We determined the accuracy of renal biopsy in predicting histological
      subtype and final Fuhrman nuclear grade in small (4 cm or smaller) renal cancers,
      and evaluated the concordance between renal biopsy and surgery for these 2
      criteria. MATERIALS AND METHODS: A total of 187 percutaneous needle biopsies of
      small renal tumors, guided by computerized tomography with gauge needles and a
      coaxial technique, were consecutively performed between 2006 and 2011. Renal cell
      carcinoma was diagnosed in 132 tumors. Partial or radical nephrectomy was
      performed for 61 of these carcinomas. Preoperative biopsy results for the
      operative specimens were compared with respect to histological subtype and
      Fuhrman nuclear grade. In addition, Kappa values were calculated as a measure of
      agreement between biopsy and surgical specimens, with correction for chance
      agreement to evaluate the concordance between biopsy and surgical classification
      for these criteria. RESULTS: Biopsy accuracy and the concordance between biopsy
      and surgery were excellent for determining histological subtype. The biopsy
      correctly identified the grade in 75% of cases, and in 93% when pooling renal
      cell carcinoma in low (1 or 2) and high (3 or 4) grade cases. The agreement
      between biopsy and surgery for Fuhrman nuclear grade was moderate (Kappa = 0.52)
      and substantial (Kappa = 0.71) when pooling low and high grade carcinoma,
      respectively. CONCLUSIONS: Although the concordance between grading on biopsy and
      with surgical specimens was moderate, likely because of the reproducibility of
      the grading system, the accuracy of biopsy for differentiating high and low grade
      small renal tumors was high, which may greatly impact decision making in cases of
      small renal cancer.

PMID- 22998911
TI  - Prognostic significance of measured depth of invasion of urothelial carcinoma of
      the bladder compared to the 2010 American Joint Committee on Cancer pT2 and pT3
      classifications.
AB  - PURPOSE: We compared the prognostic ability of the current American Joint
      Committee on Cancer (AJCC) staging system to direct measurement of the depth of
      tumor invasion into the muscularis propria and perivesical fat. MATERIALS AND
      METHODS: We identified 148 patients with pT2N0 and 206 with pT3N0 who underwent
      radical cystectomy between 1990 and 2003. Clinicopathological features were
      reviewed. A measurement in mm was recorded of the depth of tumor invasion into
      the muscularis propria for pT2 cases and into perivesical fat for pT3 cases.
      Cancer specific survival between the pT2a and pT2b, and the pT3a and pT3b patient
      groups was estimated using the Kaplan-Meier method and compared with the log rank
      test. Optimal cutoff points for invasion depth in mm were estimated using an
      iterative estimation process to find the minimum p value with the maximum HR.
      RESULTS: Of 148 patients with pT2 bladder cancer, including 76 with pT2a and 72
      with pT2b, and 206 with pT3 bladder cancer, including 144 with pT3a and 62 with
      pT3b, there was no significant difference in cancer specific survival between the
      substages (p = 0.94 and 0.37, respectively). However, patients with measured
      invasion less than 4.5 mm into perivesical fat had significantly improved cancer
      specific survival compared to that in patients with invasion 4.5 mm or greater (5
      year cancer specific survival 53% vs 40%, p = 0.02). CONCLUSIONS: We found no
      significant difference in cancer specific survival when pT2 and pT3 tumors were
      stratified by AJCC substage. However, for pT3 tumors direct measurement of the
      depth of tumor invasion into perivesical fat identified a significant
      stratification of cancer specific survival at 4.5 mm.

PMID- 22998912
TI  - Management of urethral stricture in women.
AB  - PURPOSE: We describe the diagnosis and treatment of urethral strictures in women.
      MATERIALS AND METHODS: We retrospectively identified female urethral strictures
      from 1998 to 2010. Study inclusion criteria were 1) clinical diagnosis of
      stricture, 2) stricture seen on cystoscopy, 3) urethral obstruction on
      videourodynamics according to the Blaivas-Groutz nomogram and/or 4) urethral
      caliber less than 17Fr. Postoperative recurrence was defined by the preoperative
      criteria. RESULTS: We identified 17 women with a mean age of 62 years (range 32
      to 91) with stricture. Stricture was idiopathic in 8 patients, iatrogenic in 6,
      traumatic in 2 and associated with a urethral diverticulum in 1. Videourodynamics
      could not be done in 3 women due to complete obliteration of the urethra. Ten of
      14 patients satisfied videourodynamic criteria for obstruction and 4 had impaired
      detrusor contractility. Nine women underwent vaginal flap urethroplasty,
      including 5 who also had a pubovaginal sling and 1 who had a Martius flap. One
      patient received a buccal mucosal graft as primary treatment after initial
      dilation. There was no recurrence at a minimum 1-year followup but 2 strictures
      recurred 51/2 and 6 years postoperatively, respectively. These 2 women received a
      buccal mucosal graft and were stricture free 12 to 15 months postoperatively. Of
      17 patients initially treated with urethral dilation recurrence developed in 16,
      requiring repeat dilations until urethroplasty was performed. CONCLUSIONS: In
      select women vaginal flap urethroplasty and buccal mucosal graft have high
      success rates, including 100% at 1 year and 78% at 5 years. Urethral dilation has
      a 6% success rate. Long-term followup is mandatory. Treatment should be
      individualized.

PMID- 22998913
TI  - Natural history of biochemical recurrence after radical prostatectomy with
      adjuvant radiation therapy.
AB  - PURPOSE: We evaluated the long-term outcome of patients with biochemical
      recurrence following radical prostatectomy with adjuvant radiation therapy and
      determined predictors of systemic progression in these men. MATERIALS AND
      METHODS: We identified 134 men with biochemical recurrence following radical
      prostatectomy plus adjuvant radiation therapy for pT(any)N0M0 disease. Median
      followup was 13.1 years. Survival after biochemical recurrence was estimated
      using the Kaplan-Meier method. Cox proportional hazard regression models were
      used to analyze clinicopathological variables associated with systemic
      progression after biochemical recurrence. RESULTS: Overall, 41 patients (31.5%)
      with biochemical recurrence experienced systemic progression and 57 (42.5%) died,
      including 19 (14.2%) of prostate cancer. Median systemic progression-free and
      cancer specific survival were not attained at 15 years of followup after
      biochemical recurrence. Median time from prostatectomy to recurrence was 3.3
      years. Ten-year cancer specific survival was not significantly different for
      patients who experienced biochemical recurrence less and greater than 3.3 years
      after radical prostatectomy (83% and 83%, respectively, p = 0.39). Moreover, on
      multivariate analysis increased pathological Gleason score (HR 1.78, p = 0.02)
      and rapid prostate specific antigen doubling time (less than 6-month doubling
      time HR 11.39, p <0.0001) were significantly associated with the risk of systemic
      progression. CONCLUSIONS: The natural history of biochemical recurrence after
      radical prostatectomy plus adjuvant radiation therapy is heterogeneous with only
      a minority of these men experiencing systemic progression and death from prostate
      cancer. The decision to begin additional therapies in such patients must balance
      the risk of disease progression, based on pathological Gleason score and
      postoperative prostate specific antigen doubling time, against the cost and
      morbidity of treatment.

PMID- 22998914
TI  - Health related quality of life in adolescents with bladder exstrophy-epispadias
      as measured by the Child Health Questionnaire-Child Form 87.
AB  - PURPOSE: We determined health related quality of life as reported by adolescents
      with bladder exstrophy or epispadias using a validated generic instrument.
      MATERIALS AND METHODS: Adolescents age 11 to 18 years with bladder exstrophy or
      epispadias (57) completed a validated, generic, health related quality of life
      instrument, the CHQ-CF87 (Child Health Questionnaire-Child Form 87). Urinary
      incontinence, catheterization status, and medical and surgical history data were
      also obtained. Mean summary scores and 95% CIs for each subdomain of the CHQ-CF87
      were calculated, and descriptively compared to 2 population based samples. In our
      sample health related quality of life outcomes by continence status were compared
      using univariate and multivariate analysis. However, this analysis was limited by
      a small sample size. RESULTS: Mean age of the 49 patients with bladder exstrophy
      and the 8 with epispadias was 14.3 years, 67% were male and 81% were Caucasian.
      There were 31 participants who reported incontinence and the median number of
      lifetime surgeries was 9. The exstrophy population scored well in all subdomains
      of the instrument when descriptively compared to 2 large samples of adolescent
      populations. In our sample incontinent patients had lower scores by multivariate
      analysis in 7 of 10 domains and better scores in 3 of 10 domains, although these
      differences were not statistically significant. CONCLUSIONS: Adolescents with
      bladder exstrophy and epispadias reported relatively good scores on the CHQ-CF87
      when descriptively compared to other reference populations. This finding suggests
      that these children adapt well to the challenges of their condition. Analysis of
      the association of incontinence with health related quality of life was limited
      by the small sample size.

PMID- 22998916
TI  - Clustering of UPOINT domains and subdomains in men with chronic
      prostatitis/chronic pelvic pain syndrome and contribution to symptom severity.
AB  - PURPOSE: The UPOINT (Urinary, Psychosocial, Organ specific, Infection,
      Neurologic/systemic and Tenderness of skeletal muscle) system characterizes men
      with chronic prostatitis/chronic pelvic pain syndrome according to 6 domains.
      Some domains have multiple possible criteria but to our knowledge grouping these
      criteria have never been validated. Domain clustering may provide clues to the
      etiology or treatment of individual phenotypes. We examined domain clustering
      patterns and the contribution of individual domains and subdomains to symptom
      severity. MATERIALS AND METHODS: We reviewed the records of 220 patients with
      chronic prostatitis/chronic pelvic pain syndrome. Of the patients 120 were
      characterized by UPOINT alone and 100 were characterized by subdomain, including
      urinary (voiding and storage), psychosocial (catastrophizing and depression),
      organ specific (bladder and prostate), infection (prostate and urethra) and
      neurologic/systemic. The NIH-CPSI (National Institutes of Health-Chronic
      Prostatitis Symptom Index) was used to measure symptom severity. RESULTS: The
      urinary, psychosocial, infection and neurologic/systemic subdomains had a similar
      incidence but organ specific-prostate was more common than organ specific-bladder
      (51% vs 33%). On cluster analysis with multidimensional scaling urinary, organ
      specific and tenderness clustered together, as did neurologic, infection and
      psychosocial. Of the subdomains organ specific-prostate and organ specific
      bladder diverged but the others clustered together. The domains that
      significantly contributed to the total NIH-CPSI score were urinary, psychosocial
      and tenderness. Only psychosocial contributed independently to the quality of
      life subscore. CONCLUSIONS: UPOINT domain criteria capture a homogeneous group
      for each domain except organ specific, in which bladder and prostate diverge.
      Clustering of domains specific to the pelvis (urinary, organ specific and
      tenderness) vs systemic domains (neurologic, infection and psychosocial) implies
      2 patient populations that may differ in pathophysiology and treatment response.
      The primary drivers of pain in patients with chronic pelvic pain syndrome are
      pelvic floor tenderness, depression and catastrophizing.

PMID- 22998915
TI  - Contrast enhanced transrectal ultrasound for the detection of prostate cancer: a
      randomized, double-blind trial of dutasteride pretreatment.
AB  - PURPOSE: The identification of clinically significant disease is crucial for
      optimal treatment of prostate cancer. Selective detection of prostate cancer with
      increased microvessel density is possible with contrast enhanced ultrasound.
      Preliminary studies suggest that pretreatment with a 5alpha-reductase inhibitor
      may improve the efficiency of contrast enhanced ultrasound targeted biopsy. This
      study was designed to quantify prostate cancer detection with contrast enhanced
      ultrasound with or without short-term pretreatment with dutasteride. MATERIALS
      AND METHODS: In this randomized, double-blind, placebo controlled trial of oral
      dutasteride pretreatment, contrast enhanced ultrasound findings were graded and
      used to direct targeted biopsy (up to 6 cores per prostate). A blinded 12-core
      systematic biopsy was subsequently performed on every subject based on standard
      medial and lateral sampling of each sextant. RESULTS: Of 311 subjects who
      underwent randomization, 272 completed participation. Positive biopsies were
      obtained in 276 of 3,264 (8.5%) systematic cores and 203 of 1,237 (16.4%)
      targeted cores (OR 2.1, 95% CI 1.7-2.6, p <0.001). ROC analysis for the detection
      of all prostate cancers demonstrated an increase in diagnostic accuracy from pre
      contrast imaging to contrast enhanced ultrasound (A(z) 0.60 vs 0.64, p = 0.005).
      For the detection of high grade cancer (Gleason score 7 or greater) ROC analysis
      demonstrated improved accuracy for pre-contrast imaging (A(z) 0.74) and contrast
      enhanced ultrasound (A(z) 0.80, p = 0.0005). For the detection of high grade
      cancer with greater than 50% biopsy core involvement, excellent accuracy was
      demonstrated with pre-contrast and contrast enhanced ultrasound, A(z) 0.83 and
      0.90, respectively (p = 0.001). Pretreatment with dutasteride had no significant
      impact on the detection of prostate cancer (p = 0.97). CONCLUSIONS: Contrast
      enhanced ultrasound targeted biopsy provides a significant benefit for the
      detection of high grade/high volume prostate cancer.

PMID- 22998917
TI  - Identifying children with vesicoureteral reflux: a comparison of 2 approaches.
AB  - PURPOSE: Various screening approaches have been proposed to identify the subgroup
      of children with urinary tract infection who have vesicoureteral reflux. However,
      few studies have compared the sensitivity of screening approaches in a
      representative population of young children. We compared the sensitivities of the
      top-down ((99m)technetium dimercaptosuccinic acid renal scan to screen) and
      biomarker based (C-reactive protein level at presentation) approaches in
      identifying children with vesicoureteral reflux. MATERIALS AND METHODS: We
      calculated the sensitivity of the 2 screening approaches in detecting
      vesicoureteral reflux and subsequently high grade (III or greater) vesicoureteral
      reflux in children. RESULTS: The top-down and C-reactive protein based approaches
      missed 33% and 29% of cases of high grade vesicoureteral reflux, respectively.
      CONCLUSIONS: The sensitivity of the top-down approach for detecting high grade
      vesicoureteral reflux was lower than previously reported. Further study of novel
      methods to identify children at risk for renal scarring is warranted.

PMID- 22998918
TI  - Long-term effects of endoscopic injection of dextranomer/hyaluronic acid based
      implants for treatment of urinary incontinence in children with neurogenic
      bladder.
AB  - PURPOSE: We prospectively evaluated the efficacy of dextranomer/hyaluronic acid
      based implants for the endoscopic treatment of neurogenic urinary incontinence.
      MATERIALS AND METHODS: We prospectively studied patients undergoing endoscopic
      injection of dextranomer/hyaluronic acid for structural incontinence beginning in
      October 1997. Preoperative evaluation consisted of medical history, incontinence
      charts, urine culture, urinary tract ultrasound and videourodynamics, which were
      repeated regularly during followup. At each evaluation patients were classified
      as cured or significantly improved (treatment success), or not significantly
      improved (treatment failure). Followup ranged from 1 to 13 years (mean 7.4).
      RESULTS: A total of 48 patients 5 to 20 years old with congenital (45 patients)
      or acquired (3) neurogenic bladder suffering from severe sphincteric incompetence
      were included. Of the patients 30 underwent 1, 13 underwent 2 and 5 underwent 3
      treatment sessions. Mean injected volume was 4.6 ml per session. Five patients
      had previously undergone bladder neck surgery. Two patients lost to followup in
      the short term were classified as treatment failures. Of the patients 45 had more
      than 2 years of followup, of whom 19 (39.6%) were dry, 6 (12.5%) were
      significantly improved and 23 (47.9%) had no significant improvement observed.
      Female patients achieved a significantly higher success rate than males (p =
      0.05). No significant clinical or urodynamic criterion was predictive of success
      or failure. Posttreatment bladder deterioration developed in 10 cases (7
      successes and 3 failures), which were managed by bladder augmentation.
      CONCLUSIONS: Endoscopic treatment of neurogenic urinary sphincter insufficiency
      with dextranomer/hyaluronic acid is effective in half of the patients. Recurrence
      of incontinence after 1 year is mainly a sign of bladder deterioration.

PMID- 22998919
TI  - Do Gleason patterns 3 and 4 prostate cancer represent separate disease states?
AB  - PURPOSE: The Gleason scoring system has been the traditional basis for studies on
      the assessment and treatment of prostate cancer. Recent reports of long-term
      prostate cancer outcomes stratified by Gleason score based on the 2005 ISUP
      (International Society of Urological Pathology) update suggest that important
      aspects of the biology of prostate cancer correlate with commonly available
      histopathological information. In this review we present a conceptual framework
      for the possible existence of distinct but interrelated developmental pathways in
      the context of the Gleason score in considering various biological and clinical
      aspects of prostate cancer. This may be useful in characterizing prostate cancer
      as an indolent condition in some and an aggressive disease in others, in decision
      making for treatment, and in the interpretation of the biological course and
      treatment outcomes. MATERIALS AND METHODS: A comprehensive review of clinical,
      pathological and investigational biological literature on this topic was
      conducted. In addition, the biological behavior of prostate cancer as interpreted
      from this survey was compared to that of other solid neoplasms in developing a
      schema for characterizing the pathogenesis of various forms of the disease.
      RESULTS: The Gleason scoring system has been found to have fundamental value in
      predicting the behavior of prostate cancer and assessing outcomes of its
      treatment. Increasingly, the proportion of Gleason pattern 4 in a prostatectomy
      specimen is being recognized as a critical factor in predicting the rates of
      biochemical recurrence and prostate cancer specific mortality. Under the current
      Gleason classification, a Gleason 3 + 3 = 6 cancer carries a minimal long-term
      risk of progression or mortality. Risk of biochemical recurrence and prostate
      cancer specific mortality increases with increasing proportions of the Gleason 4
      component in the prostatectomy specimen, from 3 + 3 = 6 with tertiary 4 (ie less
      than 5% of a 4 component) to 3 + 4 = 7, 4 + 3 = 7 and 4 + 4 = 8. Assuming that
      the Gleason 4 component increases in volume more rapidly with time than well
      differentiated components, it can be inferred that a smaller proportion of
      Gleason 4 could mean that the cancer has been identified at an earlier phase in
      the natural history of the disease. This could explain the improved prognosis on
      the basis of length and lead time biases, and conceivably on the basis of a
      decreased likelihood of cancer cells having metastasized. Correspondingly,
      increasing amounts of Gleason 4 cancer in a prostate specimen might be explained
      in 2 ways, as the preferential growth of a single clone of Gleason 4 cells,
      possibly with intraprostatic spread, or the evolution of Gleason 3 cancer cells
      to become Gleason 4. These hypotheses have been examined by genetic analysis of
      metastatic deposits and by comparisons of multiple foci of cancer within
      individual prostates. The clinical significance of these concepts in regard to
      disease status at diagnosis, treatment selection, outcomes of treatment, and
      implications for future research on the basis of clinical and molecular
      observations are the basis of the developmental schemata we propose. CONCLUSIONS:
      Given the relatively benign nature of homogeneous, low volume Gleason 3 tumors,
      and the progressive risk of biochemical recurrence and prostate cancer specific
      mortality with increasing quantities of Gleason 4 components, we propose that
      Gleason 4 (and 5) cancers constitute cancer diatheses distinct from that of
      Gleason 3 cancer. This distinction may contribute to the understanding of the
      prognosis intrinsic to these biological behavioral patterns, and help guide the
      translation of findings at molecular and histological levels to a more precise
      selection of treatments.

PMID- 22998920
TI  - Patient reported health related quality of life measures--what do the scores mean
      and how do they relate to patient outcomes and care?

PMID- 22998921
TI  - Factors associated with complications of the ureteral stump after proximal
      ureteroureterostomy.
AB  - PURPOSE: Ureteroureterostomy is a treatment modality for managing an ectopic
      ureterocele or ectopic ureter and preserving upper pole kidney function. However,
      the development of urinary tract infection at the residual ureteral stump is a
      concern. We analyzed factors affecting the development of urinary tract infection
      at the residual ureteral stump after proximal ureteroureterostomy. MATERIALS AND
      METHODS: Between January 2002 and December 2009 proximal ureteroureterostomy was
      performed in 80 patients with ectopic ureterocele or ectopic ureter associated
      with a duplex system. Excluding 6 patients who did not meet the study inclusion
      criteria, we investigated age at operation, diameter of the upper pole ureter on
      ultrasonography, differential renal function and the presence of vesicoureteral
      reflux in 74 patients. Risk factors for residual ureteral stump infection and
      decreased differential renal function were analyzed. RESULTS: During a median
      followup of 5.0 years an additional operation was required in 9 patients (12.2%)
      due to urinary tract infection at the residual ureteral stump a median of 2.4
      years after initial proximal ureteroureterostomy. The preoperative maximal
      diameter of the upper pole ureter was significantly greater in patients with
      infection complications. The postoperative maximal diameter of the upper pole
      ureter was also significantly greater on postoperative ultrasonography performed
      a median 43.0 days after the operation. Median preoperative and postoperative
      differential renal function was 47.8% and 47.0%, respectively. No preoperative
      factors were significantly related to the decrease in differential renal
      function. CONCLUSIONS: Proximal ureteroureterostomy is a safe treatment for
      ectopic ureterocele or ectopic ureter with a low postoperative complication rate.
      Upper pole ureter diameter was correlated with the development of a urinary tract
      infection at the residual ureteral stump.

PMID- 22998922
TI  - Minimally invasive survey in infants. Pro.

PMID- 22998923
TI  - High throughput DNA sequencing to detect differences in the subgingival plaque
      microbiome in elderly subjects with and without dementia.
AB  - BACKGROUND: To investigate the potential association between oral health and
      cognitive function, a pilot study was conducted to evaluate high throughput DNA
      sequencing of the V3 region of the 16S ribosomal RNA gene for determining the
      relative abundance of bacterial taxa in subgingival plaque from older adults with
      or without dementia. METHODS: Subgingival plaque samples were obtained from ten
      individuals at least 70 years old who participated in a study to assess oral
      health and cognitive function. DNA was isolated from the samples and a gene
      segment from the V3 portion of the 16S bacterial ribosomal RNA gene was amplified
      and sequenced using an Illumina HiSeq1000 DNA sequencer. Bacterial populations
      found in the subgingival plaque were identified and assessed with respect to the
      cognitive status and oral health of the participants who provided the samples.
      RESULTS: More than two million high quality DNA sequences were obtained from each
      sample. Individuals differed greatly in the mix of phylotypes, but different
      sites from different subgingival depths in the same subject were usually similar.
      No consistent differences were observed in this small sample between subjects
      separated by levels of oral health, sex, or age; however a consistently higher
      level of Fusobacteriaceae and a generally lower level of Prevotellaceae was seen
      in subjects without dementia, although the difference did not reach statistical
      significance, possibly because of the small sample size. CONCLUSIONS: The results
      from this pilot study provide suggestive evidence that alterations in the
      subgingival microbiome are associated with changes in cognitive function, and
      provide support for an expanded analysis of the role of the oral microbiome in
      dementia.

PMID- 22998924
TI  - Facial gunshot wound debridement: debridement of facial soft tissue gunshot
      wounds.
AB  - Over the period 1981-1985 the author treated 1486 patients with facial gunshot
      wounds sustained in combat in Afghanistan. In the last quarter of 20th century,
      more powerful and destructive weapons such as M-16 rifles, AK-47 and Kalashnikov
      submachine guns, became available and a new approach to gunshot wound debridement
      is required. Modern surgeons have little experience in treatment of such wounds
      because of rare contact with similar pathology. This article is intended to
      explore modern wound debridement. The management of 502 isolated soft tissue
      injuries is presented. Existing principles recommend the sparing of damaged
      tissues. The author's experience was that tissue sparing lead to a high rate of
      complications (47.6%). Radical primary surgical debridement (RPSD) of wounds was
      then adopted with radical excision of necrotic non-viable wound margins
      containing infection to the point of active capillary bleeding and immediate
      primary wound closure. After radical debridement wound infection and breakdown
      decreased by a factor of 10. Plastic operations with local and remote soft tissue
      were made on 14, 7% of the wounded. Only 0.7% patients required discharge from
      the army due to facial muscle paralysis and/or facial skin impregnation with
      particles of gunpowder from mine explosions. Gunshot face wound; modern
      debridement.

PMID- 22998925
TI  - Time perception at different EEG-vigilance levels.
AB  - BACKGROUND: Human time perception is influenced by various factors such as
      attention and drowsiness. Nevertheless, the impact of cerebral vigilance
      fluctuations on temporal perception has not been sufficiently explored. We
      assumed that the state of vigilance ascertained by electroencephalography (EEG)
      during the perception of a given auditory rhythm would influence its
      reproduction. Thus, we hypothesised that the re-tapping interval length and the
      accuracy of reproduction performance would vary depending on the state of
      vigilance determined by EEG. METHODS: 12 female and 9 male subjects ranging from
      21 to 38 years (M = 25.52, SD = 3.75) participated in a test paradigm comprising
      a) a resting EEG for the determination of vigilance while an auditory rhythm was
      presented, b) a short activity of the proband to be sure of sufficient alertness,
      and c) a tapping task to reproduce the presented rhythm. Vigilance states of
      three consecutive 1-sec-EEG-segments of the resting EEG before the reproduction
      phase were classified using the Vigilance Algorithm Leipzig (VIGALL). RESULTS AND
      DISCUSSION: Reproduction accuracy was more precise after high EEG-vigilance
      stages. Thus, the subjects' mean deviation from the given rhythm was lower (t(17)
      = -2.733, p < 0.05) after high vigilance stage A (MW = 0.046, SD = 0.049) than
      after low vigilance stage B (MW = 0.065, SD = 0.067). The re-tapping-length was
      significantly shorter (t(17) = -2.190, p < 0.05) for reproduction phases
      following high EEG-vigilance stage A compared to the lower EEG-vigilance stage B.
      CONCLUSION: These findings support the hypothesis of a varying time perception
      and of speed alterations of the internal clock after different states of EEG
      vigilance, which were automatically classified by VIGALL. Thus, alterations of
      cognitive processing may be assessable by specific EEG-patterns.

PMID- 22998926
TI  - Down-regulation of the caffeic acid O-methyltransferase gene in switchgrass
      reveals a novel monolignol analog.
AB  - BACKGROUND: Down-regulation of the caffeic acid 3-O-methyltransferase EC
      2.1.1.68 (COMT) gene in the lignin biosynthetic pathway of switchgrass (Panicum
      virgatum) resulted in cell walls of transgenic plants releasing more constituent
      sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases
      from an added enzyme preparation and from Clostridium thermocellum. Fermentation
      of both wild-type and transgenic switchgrass after milder hot water pretreatment
      with no water washing showed that only the transgenic switchgrass inhibited C.
      thermocellum. Gas chromatography-mass spectrometry (GCMS)-based metabolomics were
      undertaken on cell wall aqueous extracts to determine the nature of the microbial
      inhibitors. RESULTS: GCMS confirmed the increased concentration of a number of
      phenolic acids and aldehydes that are known inhibitors of microbial fermentation.
      Metabolomic analyses of the transgenic biomass additionally revealed the presence
      of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5
      hydroxycinnamyl alcohol (iso-sinapyl alcohol) in both non-pretreated, as well as
      hot water pretreated samples. iso-Sinapyl alcohol and its glucoside were
      subsequently generated by organic synthesis and the identity of natural and
      synthetic materials were confirmed by mass spectrometric and NMR analyses. The
      additional novel presence of iso-sinapic acid, iso-sinapyl aldehyde, and iso
      syringin suggest the increased activity of a para-methyltransferase, concomitant
      with the reduced COMT activity, a strict meta-methyltransferase. Quantum chemical
      calculations were used to predict the most likely homodimeric lignans generated
      from dehydration reactions, but these products were not evident in plant samples.
      CONCLUSIONS: Down-regulation of COMT activity in switchgrass resulted in the
      accumulation of previously undetected metabolites resembling sinapyl alcohol and
      its related metabolites, but that are derived from para-methylation of 5
      hydroxyconiferyl alcohol, and related precursors and products; the accumulation
      of which suggests altered metabolism of 5-hydroxyconiferyl alcohol in
      switchgrass. Given that there was no indication that iso-sinapyl alcohol was
      integrated in cell walls, it is considered a monolignol analog. Diversion of
      substrates from sinapyl alcohol to free iso-sinapyl alcohol, its glucoside, and
      associated upstream lignin pathway changes, including increased phenolic
      aldehydes and acids, are together associated with more facile cell wall
      deconstruction, and to the observed inhibitory effect on microbial growth.
      However, iso-sinapyl alcohol and iso-sinapic acid, added separately to media,
      were not inhibitory to C. thermocellum cultures.

PMID- 22998927
TI  - Comparison of emergency department and hospital admissions data for air pollution
      time-series studies.
AB  - BACKGROUND: Emergency department (ED) visit and hospital admissions (HA) data
      have been an indispensible resource for assessing acute morbidity impacts of air
      pollution. ED visits and HAs are types of health care visits with similarities,
      but also potentially important differences. Little previous information is
      available regarding the impact of health care visit type on observed acute air
      pollution-health associations from studies conducted for the same location, time
      period, outcome definitions and model specifications. METHODS: As part of a
      broader study of air pollution and health in St. Louis, individual-level ED and
      HA data were obtained for a 6.5 year period for acute care hospitals in the eight
      Missouri counties of the St. Louis metropolitan area. Patient demographic
      characteristics and diagnostic code distributions were compared for four visit
      types including ED visits, HAs, HAs that came through the ED, and non-elective
      HAs. Time-series analyses of the relationship between daily ambient ozone and
      PM2.5 and selected cardiorespiratory outcomes were conducted for each visit type.
      RESULTS: Our results indicate that, compared with ED patients, HA patients tended
      to be older, had evidence of greater severity for some outcomes, and had a
      different mix of specific outcomes. Consideration of 'HA through ED' appeared to
      more effectively select acute visits than consideration of 'non-elective HA'.
      While outcomes with the strongest observed temporal associations with air
      pollutants tended to show strong associations for all visit types, we found some
      differences in observed associations for ED visits and HAs. For example, risk
      ratios for the respiratory disease-ozone association were 1.020 for ED visits and
      1.004 for 'HA through ED'; risk ratios for the asthma/wheeze-ozone association
      were 1.069 for ED visits and 1.106 for 'HA through ED'. Several factors (e.g.
      age) were identified that may be responsible, in part, for the differences in
      observed associations. CONCLUSIONS: Demographic and diagnostic differences
      between visit types may lead to preference for one visit type over another for
      some questions and populations. The strengths of observed associations with air
      pollutants sometimes varied between different health care visit types, but the
      relative strengths of association generally were specific to the pollutant
      outcome combination.

PMID- 22998929
TI  - Protein fibrillation and the olfactory system: speculations on their linkage.

PMID- 22998928
TI  - Pancreatic and thyroid metastases detected with 18F-FDG PET/CT in patient with
      colorectal cancer.
AB  - A 53-year-old woman with diagnosis of colorectal cancer, who received surgical
      treatment and chemotherapy. After 5-years of complete remission, she showed an
      atypical oncological evolution. The utility of (18)F-FDG PET/CT scan has been
      fundamental to detect suspected and unsuspected recurrence and to monitor
      response to treatment.

PMID- 22998930
TI  - [The reading brain].
AB  - Reading is at the core of most current cultural achievements, including
      literature and science. Cognitive neurosciences now allow us to understand how
      this crucial cultural construct, its operation, development and breakdown, is
      rooted in the biological constraints of brain function.

PMID- 22998932
TI  - Estrogen augmentation in schizophrenia: a quantitative review of current
      evidence.
AB  - BACKGROUND: Sex differences in the incidence, onset and course of schizophrenia
      have led to the hypothesis that estrogens play a protective role in the
      pathophysiology of this disorder. Several trials have assessed the potential of
      estrogens in reducing schizophrenia symptoms, showing inconsistent results. This
      quantitative review summarizes available evidence on the efficacy of estrogens in
      the treatment of schizophrenia. METHODS: Only double-blind, placebo-controlled,
      randomized studies were included. Primary outcome measure was total symptom
      severity, secondary outcome measures were subscores for positive and negative
      symptoms. Effect sizes were calculated for individual studies and, if possible,
      pooled in meta-analyses to obtain combined, weighted effect sizes (Hedges's g).
      RESULTS: Superior efficacy was found for estrogen treatment in female patients
      (four RCTs, 214 patients) on total symptom severity (Hedges's g=0.66), although
      heterogeneity was moderate to high. Estrogens were also superior in reducing
      positive (Hedges's g=0.54) and negative symptoms (Hedges's g=0.34), with low
      heterogeneity. As the included studies applied different forms of estrogens, a
      separate analysis was conducted on the trials applying estradiol (three RCTs, 170
      patients). Even larger effect sizes were found for total symptom severity
      (Hedges's g=0.79), positive (Hedges's g=0.57) and negative symptoms (Hedges's
      g=0.45), with reduced heterogeneity. Estrogen treatment in male patients (one
      study, 53 patients) was not superior to placebo. CONCLUSIONS: Our results suggest
      that estrogens, especially estradiol, could be an effective augmentation strategy
      in the treatment of women with schizophrenia. However, future larger trials are
      needed before recommendations on clinical applications can be made.

PMID- 22998931
TI  - Leisure time activities in adolescence in the presence of susceptibility genes
      for obesity: risk or resilience against overweight in adulthood? The HUNT study.
AB  - BACKGROUND: Environment, health behavior, and genetic background are important in
      the development of obesity. Adolescents spend substantial part of daily leisure
      time on cultural and social activities, but knowledge about the effects of
      participation in such activities on weight is limited. METHODS: A number of 1450
      adolescents from the Norwegian HUNT study (1995-97) were followed-up in 2006-08
      as young adults. Phenotypic data on lifestyle and anthropometric measures were
      assessed using questionnaires and standardized clinical examinations. Genotypic
      information on 12 established obesity-susceptibility loci were available for
      analyses. Generalized estimating equations were used to examine the associations
      between cultural and social activities in adolescence and adiposity measures in
      young adulthood. In addition, interaction effects of a genetic predisposition
      score by leisure time activities were tested. RESULTS: In girls, participation in
      cultural activities was negatively associated with waist circumference (WC) (B = 
      0.04, 95%CI: -0.08 to -0.00) and with waist-hip ratio (WHR) (B = -0.058, 95%CI: 
      0.11 to -0.01). However, participation in social activities was positively
      associated with WC (B = 0.040, CI: 0.00 to 0.08) in girls and with BMI (B =
      0.027, CI: 0.00 to 0.05) in boys. The effect of the obesity-susceptibility
      genetic variants on anthropometric measures was lower in adolescents with high
      participation in cultural activities compared to adolescents with low
      participation. CONCLUSION: This study suggests that the effects of cultural
      activities on body fat are different from the effects of participation in social
      activities. The protective influence of cultural activities in female adolescents
      against overweight in adulthood and their moderating effect on obesity
      susceptibility genes suggest that even cultural activities may be useful in
      public health strategies against obesity.

PMID- 22998933
TI  - Regional cortical thinning in subjects with high genetic loading for
      schizophrenia.
AB  - OBJECTIVE: Although recent studies have revealed regional cortical thinning in
      patients with schizophrenia, it is not clear whether cortical thinning reflects a
      genetic liability for schizophrenia. The present study investigated the change of
      cortical thickness in subjects at genetic high risk (GHR) for schizophrenia with
      a relatively high genetic loading compared with healthy controls (HC) and
      patients with schizophrenia. The effect of genetic loading on cortical thinning
      was also measured by comparing GHR subgroups according to the levels of genetic
      loading. METHODS: Cortical thickness was measured by the Constrained Laplacian
      based Automated Segmentation with Proximities algorithm using 1.5-T structural
      MRI scans. The cortical thickness of the subjects at GHR (n=31) was compared with
      that of HC (n=29) and patients with schizophrenia (n=31). We then compared the
      cortical thickness of the GHR subgroups according to the number of first-degree
      relatives with schizophrenia to measure the effect of genetic loading. RESULTS:
      Relative to HC, GHR subjects showed significant cortical thinning in the right
      anterior cingulate cortex (ACC), left paracingulate and posterior cingulate
      regions; bilateral frontal regions including frontal pole and ventromedial
      prefrontal cortex; bilateral temporal regions including the left parahippocampal
      gyrus; and bilateral inferior parietal and occipital regions; however, patients
      with schizophrenia showed more widespread cortical thinning in the fronto-temporo
      parietal region. GHR subjects who had two or more first-degree relatives with
      schizophrenia showed a greater reduction in cortical thickness in the right ACC
      and in the left paracingulate cortex than did those who had only one first-degree
      relative with schizophrenia. CONCLUSION: Our findings suggest that the level of
      genetic loading may have a dose-dependent effect on cortical thinning in the
      right ACC and in the left paracingulate cortex and that cortical thinning in GHR
      subjects may represent neurodevelopmental alterations that result from genetic
      liability for schizophrenia.

PMID- 22998934
TI  - Foreword.
AB  - Pattern finding in biomolecular data is at the core of Computational Molecular
      Biology research. Indeed, it makes a very important contribution in the analysis
      of these data. It can reveal information about shared biological functions of
      biological macromolecules, coming from several different organisms, by the
      identification of patterns that are shared by structures related to these
      macromolecules. These patterns, which have been conserved during evolution, often
      play an important structural and/or functional role, and consequently, shed light
      on the mechanisms and the biological processes in which these macromolecules
      participate. Pattern finding in biomolecular data is also used in evolutionary
      studies, in order to analyze relationships that exist between species and
      establish if two, or several, biological macromolecules are homologous and to
      reconstruct the  phylogenetic tree that links them to their common biological
      ancestor. On the other hand, with the new sequencing technologies, the number of
      biological sequences in databases is increasing exponentially. In addition, the
      lengths of these sequences are large. Hence, the finding of patterns in such
      databases requires the development of fast, low memory requirement and
      highperformance techniques and approaches. This issue contains very interesting
      papers that deal with pattern finding in Computational Molecular Biology.

PMID- 22998935
TI  - Nasal polyposis in lung transplant recipients with cystic fibrosis.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyposis is common in patients
      with cystic fibrosis (CF). There are still many open questions regarding factors
      related to this condition. Furthermore, the prevalence of nasal polyposis and its
      implications for the outcomes in lung transplant recipients with cystic fibrosis
      are unknown. METHODS: All CF patients who underwent lung transplantation at our
      centre between November 1992 and December 2009 were included. Nasal polyp status
      was determined endoscopically at time sinus surgery and its relationships to
      gender, age at lung transplantation, Liou raw score, body mass index,
      FEV1%predicted, diabetes mellitus, pre-transplant pseudomonas colonisation of the
      sinuses and the lungs, pre-transplant corticosteroid use and type of mutation of
      the CFTR gene were analysed. The post-transplant survival times and the incidence
      of bronchiolitis obliterans syndrome in patients with or without nasal polyposis
      were compared. RESULTS: Nasal polyps were found in 19% (17 patients) of the 89
      lung transplant recipients, whose data was available for statistical analysis.
      None of the factors analysed was related to the nasal polyp status. The post
      transplant survival times and the incidence of bronchiolitis obliterans syndrome
      did not significantly differ between patients with or without nasal polyposis.
      CONCLUSIONS: CF-related nasal polyposis occurs in a relevant fraction of lung
      transplant recipients. A specific effect of nasal polyposis on post-transplant
      outcome could not be confirmed. Nevertheless, there was a trend to NP recurrence
      in patients with post-transplant sinonasal pseudomonas colonisation and is a
      tendency of less chronic rejection in CF patients with nasal polyps.

PMID- 22998936
TI  - Characterization of a recurrent 3.8kb deletion involving exons 17a and 17b within
      the CFTR gene.
AB  - BACKGROUND: Large deletions within CFTR have been estimated to constitute 1-2%
      pathogenic alleles, but the occurrence could be much higher in classical cystic
      fibrosis (CF) patients with one mutation detectable by the routine
      screening/sequencing work-up. Currently, evaluation of major CFTR rearrangements
      is not included in the mutation analysis for the reproductive partner of a CF
      patient/carrier. METHODS: Exon sequencing and Multiplex Ligation-dependent
      Amplification (MLPA) analyses were used to make a molecular diagnosis of two
      unrelated CF patients. Long PCR, restriction mapping, cloning, and hot start
      sequencing were employed to accurately annotate the rearrangement junctions.
      RESULTS: Both patients had a heterozygous single amino acid deletion mutation
      identified by sequencing, and a heterozygous deletion of CFTR exons 17a and 17b
      detected by MLPA. Molecular characterization of the rearrangement breakpoints
      indicated that the two patients had an identical complex
      c.2988+1616_c.3367+356del3796ins62 change, flanked by a pair of perfectly
      inverted repeats of 32 nucleotides. CONCLUSIONS: The
      c.2988+1616_c.3367+356del3796ins62 complex rearrangement is a recurrent mutation
      from patients of different ethnic backgrounds. This mutation can be detected
      through a simple PCR based analysis.

PMID- 22998937
TI  - Single high-dose oral vitamin D3 (stoss) therapy--a solution to vitamin D
      deficiency in children with cystic fibrosis?
AB  - OBJECTIVES: To determine the safety and efficacy of stoss therapy on vitamin D
      levels over a 12 month period in children with cystic fibrosis and vitamin D
      deficiency (<75 nmol/L). STUDY DESIGN: Retrospective chart review of 142
      paediatric CF patients from 2007 till 2011. RESULTS: Thirty eight children
      received stoss therapy and 37 children with vitamin D deficiency were not treated
      and served as a control group. The stoss treated group had a significant and
      sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12
      months post treatment compared to controls (94.82 +/- 41.0 nmol/L, p=0.001; 81.54
      +/- 24.6 nmol/L, p=0.001; 92.18 +/- 36.5 nmol/L, p=0.008 and 64.6 +/- 20.0
      nmol/L, p=0.006 respectively). At 12 months post intervention, the mean
      difference in vitamin D levels from baseline between the stoss treated group and
      controls was significant at 15 nmol/L compared to 5 nmol/L (p=0.038). CONCLUSION:
      Stoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D
      greater than 75 nmol/L over 12 months.

PMID- 22998938
TI  - [Aetiological classification of ischaemic strokes: comparison of the new A-S-C-O
      classification and the classification by the Spanish Society of Neurology's
      Cerebrovascular Disease Study Group].
AB  - INTRODUCTION: The A-S-C-O classification may be better than other methods for
      classifying ischaemic stroke by aetiology. Our aims are to describe A-S-C-O
      phenotype distribution (A: atherosclerosis, S: small vessel disease, C: cardiac
      source, O: other causes; 1: potential cause, 2: causality uncertain, 3: unlikely
      to be a direct cause although disease is present) and compare them to the Spanish
      Society of Neurology's Cerebrovascular Disease Study Group (GEECV/SEN)
      classification. We will also find the degree of concordance between these
      classification methods and determine whether using the A-S-C-O classification
      delivers a smaller percentage of strokes of undetermined cause. METHODS: We
      analysed those patients with ischaemic stroke admitted to our stroke unit in 2010
      with strokes that were classified according to GEECV/SEN and A-S-C-O criteria.
      RESULTS: The study included 496 patients. The percentages of strokes caused by
      atherosclerosis and small vessel disease according to GEECV/SEN criteria were
      higher than the percentages for potential atherosclerotic stroke (A1) (14.1 vs.
      11.9%; P=.16) and potential small vessel stroke (S1) (14.3 vs. 3%; P<.001).
      Cardioembolic stroke (C1) was more frequent (22.2 vs. 31%; P<.001). No
      differences between unusual cause of stroke and other potential causes (O1) were
      observed. Some degree of atherosclerosis was present in 53.5% of patients (A1,
      A2, or A3); 65.5% showed markers of small vessel disease (S1, S2, or S3), and
      74.9% showed signs of cardioembolism (C1, C2, or C3). Fewer patients in the group
      without scores of 1 or 2 for any of the A-S-C-O phenotypes were identified as
      having a stroke of undetermined cause (46.6 vs. 29.2%; P<.001). The agreement
      between the 2 classifications ranged from kappa<0.2 (small vessel and S1) to
      kappa>0.8 (unusual causes and O1). CONCLUSION: Our results show that GEECV/SEN
      and A-S-C-O classifications are neither fully comparable nor consistent. Using
      the A-S-C-O classification provided additional information on co-morbidities and
      delivered a smaller percentage of strokes classified as having an undetermined
      cause.

PMID- 22998939
TI  - Foveal vision is impaired in Parkinson's disease.
AB  - PURPOSE: The article aims to review foveal involvement in Parkinson's disease.
      SCOPE: Clinical observations as well as electrophysiological and anatomical
      studies in animal models provide evidence that Parkinson's disease (PD) affects
      vision. The retina is the most distal locus of visual dysfunction in PD as shown
      by electroretinographic (ERG) and optical coherence tomographic (OCT) studies.
      Thinning of the retinal nerve fibre layer (RNFL) and the fovea has been reported
      in PD. This review summarises retinal physiology and foveal visual dysfunction in
      PD and quantification of retinal thinning as reported in different studies and
      using different instruments. At this point due to methodological diversity and
      relatively low number of subjects studied, a meta-analysis is not yet possible.
      Results obtained on one equipment are not yet transferable to another. The author
      also briefly alludes to some links of visual processing deficits beyond visual
      detection, such as visual discrimination, visual categorisation and visuospatial
      orientation in PD. CONCLUSIONS: There are some promising results suggesting the
      potential applicability of ST-Oct as a biomarker in PD. Furthermore, these data
      raise some interesting neurobiological questions. However, there are identifiable
      pitfalls before OCT quantification may be used as a biomarker in PD. Analysis
      standardisation is needed on a larger than existing healthy and patient
      population. Furthermore, longitudinal studies are needed. The exact relationship
      between retinal foveal deficits and visuo-cognitive impairment in PD remains a
      challenging research question.

PMID- 22998941
TI  - Endemicity of leptospirosis in domestic and wild animal species from Reunion
      Island (Indian Ocean).
AB  - Leptospirosis is the major infectious disease on Reunion Island but little is
      known about the animal reservoir. We conducted a wide-ranging survey that
      included samples from 574 animals belonging to 12 species. The seroprevalence and
      prevalence of renal carriage varied greatly depending on the species, with the
      highest seroprevalence (79.5%) found in Norway rats, and the lowest (13.2%) in
      tenrecs. The renal carriage rate ranged from 84.6% in mice to 0% in tenrecs. Our
      results suggest that rodents are the most important reservoirs of leptospirosis
      on Reunion Island. The epidemiological role that animals play in human infection
      is discussed. For the first time, we quantified the renal concentration of
      leptospires in ten naturally infected mammals. The history of Reunion Island
      colonization probably explains why the circulating Leptospira serogroups were
      similar to those found in Europe. Our study provides evidence that will help
      implement preventive measures against this zoonosis.

PMID- 22998942
TI  - A role for TLR1, TLR2 and NOD2 in cytokine induction by Bacteroides fragilis.
AB  - Bacteroides fragilis, an intestinal flora commensal microorganism, is frequently
      isolated from abscesses and soft tissue infections. This study aimed to identify
      pattern recognition receptors (PRRs) involved in B. fragilis recognition and to
      characterize the induced cytokine profile. Human PBMCs were stimulated with heat
      killed B. fragilis and cytokine levels were determined by ELISA. Roles of
      individual PRRs were assessed using specific blockers of receptor signaling
      pathways and PBMCs carrying single nucleotide polymorphisms of PRR genes. Cell
      lines expressing human TLR2 or TLR4 were employed to assess TLR-specificity of B.
      fragilis. TLR1, TLR2 and NOD2 were the main PRRs responsible for recognition of
      B. fragilis, while TLR4, TLR6, NOD1 and Dectin-1 were not involved. B. fragilis
      induced strong IL-6 and IL-8, moderate IL-1beta and TNF-alpha, and poor IL-10, IL
      17, IL-23 and IFN-gamma production. This study identifies the receptor pathways
      of the innate immune response to B. fragilis, and thus provides new insights in
      the host defense against B. fragilis.

PMID- 22998943
TI  - A constraint-based model of Scheffersomyces stipitis for improved ethanol
      production.
AB  - BACKGROUND: As one of the best xylose utilization microorganisms,
      Scheffersomyces stipitis exhibits great potential for the efficient
      lignocellulosic biomass fermentation. Therefore, a comprehensive understanding of
      its unique physiological and metabolic characteristics is required to further
      improve its performance on cellulosic ethanol production. RESULTS: A constraint
      based genome-scale metabolic model for S. stipitis CBS 6054 was developed on the
      basis of its genomic, transcriptomic and literature information. The model iTL885
      consists of 885 genes, 870 metabolites, and 1240 reactions. During the
      reconstruction process, 36 putative sugar transporters were reannotated and the
      metabolisms of 7 sugars were illuminated. Essentiality study was conducted to
      predict essential genes on different growth media. Key factors affecting cell
      growth and ethanol formation were investigated by the use of constraint-based
      analysis. Furthermore, the uptake systems and metabolic routes of xylose were
      elucidated, and the optimization strategies for the overproduction of ethanol
      were proposed from both genetic and environmental perspectives. CONCLUSIONS:
      Systems biology modelling has proven to be a powerful tool for targeting
      metabolic changes. Thus, this systematic investigation of the metabolism of S.
      stipitis could be used as a starting point for future experiment designs aimed at
      identifying the metabolic bottlenecks of this important yeast.

PMID- 22998944
TI  - Interval compressed vincristine, doxorubicin, cyclophosphamide alternating with
      ifosfamide, etoposide in patients with advanced Ewing's and other Small Round
      Cell Sarcomas.
AB  - BACKGROUND: To evaluate tolerability and maintenance of dose intensity of 2
      weekly treatment with vincristine, doxorubicin, cyclophosphamide alternating with
      ifosfamide, etoposide (VDC/IE) in patients with advanced small round cell
      sarcomas including Ewing family tumours (EFT), desmoplastic small round cell
      tumours (DSRCT) and undifferentiated high grade round cell sarcomas (UHGRCS).
      METHODS: Retrospective review of 16 patients treated at a single centre with
      VDC/IE. Dose received, treatment delay, toxicity and clinical outcome were
      recorded for each cycle up to a maximum of 14 cycles. RESULTS: A total 193 cycles
      of VDC/IE were administered to 10 patients with EFT, 4 with DSRCT and 2 with
      UHGRCS. Median age was 22 years with 75% over 18 years. Metastases were present
      in 14 patients. The mean duration of each cycle was 16.7 days. Febrile
      neutropenia occurred in 14 % of cycles, and grade 3/4 haematologic toxicity
      including anaemia and thrombocytopenia in 16 % and 11 % of cycles respectively.
      Seven patients had a dose reduction. Five patients discontinued VDC/IE early due
      to toxicity. CONCLUSIONS: This schedule of VDC/IE is feasible in patients with
      EFT and DSRCT including adults and those with metastases. Its comparison with
      other standard regimens for these diseases is justified.

PMID- 22998945
TI  - Displaying R spatial statistics on Google dynamic maps with web applications
      created by Rwui.
AB  - BACKGROUND: The R project includes a large variety of packages designed for
      spatial statistics. Google dynamic maps provide web based access to global maps
      and satellite imagery. We describe a method for displaying directly the spatial
      output from an R script on to a Google dynamic map. METHODS: This is achieved by
      creating a Java based web application which runs the R script and then displays
      the results on the dynamic map. In order to make this method easy to implement by
      those unfamiliar with programming Java based web applications, we have added the
      method to the options available in the R Web User Interface (Rwui) application.
      Rwui is an established web application for creating web applications for running
      R scripts. A feature of Rwui is that all the code for the web application being
      created is generated automatically so that someone with no knowledge of web
      programming can make a fully functional web application for running an R script
      in a matter of minutes. RESULTS: Rwui can now be used to create web applications
      that will display the results from an R script on a Google dynamic map. Results
      may be displayed as discrete markers and/or as continuous overlays. In addition,
      users of the web application may select regions of interest on the dynamic map
      with mouse clicks and the coordinates of the region of interest will
      automatically be made available for use by the R script. CONCLUSIONS: This method
      of displaying R output on dynamic maps is designed to be of use in a number of
      areas. Firstly it allows statisticians, working in R and developing methods in
      spatial statistics, to easily visualise the results of applying their methods to
      real world data. Secondly, it allows researchers who are using R to study health
      geographics data, to display their results directly onto dynamic maps. Thirdly,
      by creating a web application for running an R script, a statistician can enable
      users entirely unfamiliar with R to run R coded statistical analyses of health
      geographics data. Fourthly, we envisage an educational role for such
      applications.

PMID- 22998946
TI  - Age-dependent decline in learning and memory performances of WAG/Rij rat model of
      absence epilepsy.
AB  - Recent clinical studies revealed emotional and cognitive impairments associated
      with absence epilepsy. Preclinical research with genetic models of absence
      epilepsy however have primarily focused on dysfunctional emotional processes and
      paid relatively less attention to cognitive impairment. In order to bridge this
      gap, we investigated age-dependent changes in learning and memory performance,
      anxiety-like behavior, and locomotor activity of WAG/Rij rats (a valid model of
      generalized absence epilepsy) using passive avoidance, Morris water maze,
      elevated plus maze, and locomotor activity cage. We tested 5 month-old and 13
      month-old WAG/Rij rats and compared their performance to age-matched Wistar rats.
      Results revealed a decline in emotional and spatial memory of WAG/Rij rats
      compared to age-matched Wistar rats only at 13 months of age. Importantly, there
      were no significant differences between WAG/Rij and Wistar rats in terms of
      anxiety-like behavior and locomotor activity at either age. Results pointed at
      age-dependent learning and memory deficits in the WAG/Rij rat model of absence
      epilepsy.

PMID- 22998947
TI  - Is primary tumor volume still a prognostic factor in intensity modulated
      radiation therapy for nasopharyngeal carcinoma?
AB  - BACKGROUND AND PURPOSE: To evaluate the prognostic value of gross primary tumor
      volume (GTV-P) in nasopharyngeal carcinoma (NPC) patients treated with intensity
      modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 694
      nonmetastatic and histologically proven NPC patients who underwent IMRT were
      retrospectively reviewed. Samples were split randomly into a training set (n=232)
      and a test set (n=462) to analysis. The receiver operating characteristic (ROC)
      curves were calculated to identify the cut-off point and test the prognostic
      validity of the GTV-P. The correlations between GTV-P and the American Joint
      Committee on Cancer (AJCC) disease stages were also analyzed. RESULTS: The 5-year
      disease-free survival (DFS), overall survival (OS), local relapse-free survival
      (LRFS) and distant metastasis-free survival (DMFS) rates for NPC patients with
      GTV-P<19 vs. >=19 ml were 94.9% vs. 64.8%, 97.0% vs. 76.4%, 98.2% vs. 92.5% and
      97.1% vs. 75.2%, respectively (all P<0.05) in all patients. Multivariate analysis
      indicated GTV-P was an independent prognostic factor. The ROC curve verified that
      the predictive ability of T classifications was improved when combined with GTV-P
      (P<0.001). CONCLUSIONS: GTV-P is an independent prognostic indicator for
      treatment outcome after IMRT, and significantly improves the prognostic validity
      of T classifications in NPC.

PMID- 22998948
TI  - Glucocorticoid excess and the developmental origins of disease: two decades of
      testing the hypothesis--2012 Curt Richter Award Winner.
AB  - Low birthweight, a marker of an adverse in utero environment, is associated with
      cardiometabolic disease and brain disorders in adulthood. The adaptive changes
      made by the fetus in response to the intra-uterine environment result in
      permanent changes in physiology, structure and metabolism, a phenomenon termed
      early life programming. One of the key hypotheses to explain programming, namely
      over exposure of the developing fetus to glucocorticoids, was proposed nearly two
      decades ago, following the observation that the fetus was protected from high
      glucocorticoid levels in the mother by the actions of the placental barrier
      enzyme, 11beta-hydroxysteroid dehydrogenase, which converts active
      glucocorticoids into inactive products. Numerous mechanistic studies in animal
      models have been carried out to test this hypothesis using manipulations to
      increase maternal glucocorticoids. Overall, these have resulted in offspring of
      lower birthweight, with an activated hypothalamic-pituitary-adrenal (HPA) axis
      and an adverse metabolic profile and behavioural phenotype in adulthood. Altered
      glucocorticoid activity or action is a good candidate mechanism in humans to link
      low birthweight with cardiometabolic and brain disorders. We have carried out
      detailed studies in men and women showing that high levels of endogenous
      glucocorticoids, or treatment with exogenous glucocorticoids, is associated with
      an adverse metabolic profile, increased cardiovascular disease and altered mood
      and cognitive decline. Our laboratory carried out the first translational studies
      in humans to test the glucocorticoid hypothesis, firstly demonstrating in studies
      of adult men and women, that low birthweight was associated with high fasting
      cortisol levels. We went on to dissect the mechanisms underlying the high fasting
      cortisol, demonstrating activation of the HPA axis, with increased cortisol
      responses to stimulation with exogenous adrenocorticotrophin hormone, lack of
      habituation to the stress of venepuncture, and increased cortisol responses to
      psychosocial stress. We have developed new dynamic tests to dissect the
      mechanisms regulating HPA axis central negative feedback sensitivity in humans,
      and demonstrated that this may be altered in obesity, one component of the
      metabolic syndrome. There are now studies in humans demonstrating that high
      circulating levels of maternal cortisol during pregnancy correlate negatively
      with birthweight, suggesting that excess glucocorticoids can by-pass the
      placental barrier. Deficiencies in the barrier enzyme, potentially increasing
      fetal glucocorticoid exposure, can also arise in association with maternal
      stress, malnutrition and disease, and can be inhibited by consumption of
      liquorice, which contains glycyrrhizin, an HSD inhibitor. Importantly, studies in
      humans have now demonstrated that high maternal cortisol in pregnancy and/or
      inhibition of HSD2 are associated with programmed outcomes in childhood including
      higher blood pressure, behavioural disorders as well as altered brain structure.
      We are investigating this further, using novel magnetic resonance imaging
      techniques to study the developing fetal brain in utero. The translational
      studies in support of the glucocorticoid hypothesis, and demonstrating that
      glucocorticoids are both mediators and targets of programming, are exciting and
      raise the question of whether this information can be used to identify those
      individuals most at risk of later life disease. In a recent study we showed that
      alterations in DNA methylation at genes important in regulating cortisol levels,
      tissue glucocorticoid action, blood pressure and fetal growth, are present in
      adulthood in association with both early life parameters and cardiometabolic risk
      factors. These preliminary data add to the limited literature in humans
      indicating a persisting epigenetic link between early life events and subsequent
      disease risk. Such findings open novel avenues for further exploration of the
      contribution of glucocorticoids to later life disease.

PMID- 22998950
TI  - Chemical and thermal unfolding of calreticulin.
AB  - Calreticulin is a soluble endoplasmic reticulum chaperone, which has a relatively
      low melting point due to its remarkable structure with a relatively high content
      of flexible structural elements. Using far ultraviolet circular dichroism (CD)
      spectroscopy and a fluorescent dye binding thermal shift assay, we have
      investigated the chemical and thermal stability of calreticulin. When the
      chemical stability of calreticulin was assessed, a midpoint for calreticulin
      unfolding was calculated to 3.0M urea using CD data at 222 nm. Using the
      fluorescent dye binding thermal shift assay, calreticulin was found to obtain a
      molten structure in urea concentrations between 1-1.5 M urea, and to
      unfold/aggregate at high and low pH values. The results demonstrated that the
      fluorescent dye binding assay could measure the thermal stability of calreticulin
      in aqueous buffers with results comparable to melting points obtained by other
      techniques.

PMID- 22998949
TI  - Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe
      Heritable Hyperlipidemic rabbits.
AB  - Oxytocin (OT) is a neurohypophyseal peptide traditionally associated with female
      reproductive functioning, and more recently with prosocial behavior. OT and its
      receptor are also expressed in the heart and vascular tissue and play a role in
      cardiovascular homeostasis. In vitro, it has been demonstrated that OT decreases
      NADPH-dependent superoxide production and pro-inflammatory cytokine release from
      vascular endothelial cells and macrophages, suggesting that OT may attenuate
      pathophysiological processes involved with atherosclerotic lesion formation. The
      present study sought to determine the effect of chronic exogenous OT
      administration on inflammation and atherosclerosis in an animal model of
      dyslipidemia and atherosclerosis, the Watanabe Heritable Hyperlipidemic (WHHL)
      rabbit. Twenty-two, 3-month-old WHHLs were surgically implanted with osmotic mini
      pumps containing OT (n=11) or vehicle (n=11), and then were individually housed
      for the entire study. Blood and 24-h urine samples were taken at baseline and
      after 8 (midpoint) and 16 (endpoint) weeks of treatment. At endpoint, the aortas
      and visceral fat samples were dissected and stored for analyses. There were no
      group differences in body weight, serum lipids, plasma/urinary measures of
      oxidative stress, plasma cortisol or urinary catecholamines over the 16-week
      treatment. OT-treated animals exhibited significantly lower plasma C-reactive
      protein levels at midpoint and endpoint and developed significantly less
      atherosclerosis in the thoracic aorta relative to vehicle control animals at
      endpoint (p<0.05). Cytokine gene expression from visceral adipose tissue samples
      suggested that there was a decrease in adipose tissue inflammation in the OT
      treated group compared to the vehicle control group, however these differences
      were not statistically significant. These results suggest that chronic peripheral
      OT administration can inhibit inflammation and atherosclerotic lesion
      development.

PMID- 22998951
TI  - Seroprevalence and national distribution of human toxoplasmosis in Mexico:
      analysis of the 2000 and 2006 National Health Surveys.
AB  - Global warming has had serious implications on dispersion of infectious diseases
      like toxoplasmosis. Since the frequency of Toxoplasma gondii largely depends on
      climatic conditions, we studied its prevalence by means of 3599 samples of the
      National Health Survey 2000 (NHS-2000) and 2916 of the National Health and
      Nutrition Survey 2006 (NHNS-2006) serum banks, obtained from 1-98 year old
      subjects of both genders and all states of Mexico. Anti-T.gondii IgG antibodies
      were determined by ELISA and confirmed by western blot. Crude, epidemiologically
      weighted and diagnosis-performance-adjusted prevalence values were calculated.
      Seroprevalence changes were compared between both surveys and among regions
      (north, center and coast). Also, correlations between changes in temperature or
      humidity and those in prevalence were measured. National crude prevalence was
      60.1% and 62.6% for NHS-2000 and NHNS-2006, respectively. Weighted and adjusted
      values were 62.5% and 40.0% for NHS-2000, and 63.7 and 43.1% for NHNS-2006.
      Coastal states and children presented the largest increases between surveys,
      while the center of the country showed a decrease. An apparently higher
      prevalence of T. gondii infection was observed in both surveys compared to that
      performed in 1987, while a geographical re-distribution was found from 2000 to
      2006, with a positive correlation between temperature and frequency deltas in 21
      states where prevalence increased.

PMID- 22998952
TI  - The predictive value of a maculopapular rash in children hospitalized for dengue
      fever in Cayenne, French Guiana.
AB  - In order to determine the predictive value of a rash during dengue fever, a
      cohort study was conducted in children hospitalized for dengue during an epidemic
      in French Guiana. A rash was predictive of uncomplicated dengue: the HR of
      developing a severe form of disease was 0.43 (95% CI 0.21-0.88; p-value=0.021)
      for patients with rash.

PMID- 22998953
TI  - Oral infection, regular alcohol drinking pattern, and myocardial infarction.
AB  - Oral infections have been associated with an increased risk for myocardial
      infarction (MI) and other cardiovascular diseases (CVD). Conversely, low, regular
      alcohol consumption is associated with a lower association of CVD. The objective
      was to test the novel hypothesis that oral infections are modified by regular
      alcohol drinking which has the effect of lowering the incidence of MI's. The
      effect has been observed where tooth extractions where carried out due to
      infections and compared with extractions unconnected to infections. Oral
      infections and in particular periodontal infections impose an infectious load on
      the health in many people. In its advanced forms (periodontal pockets >= 6mm)
      periodontitis affects ~10-15% of adults. The infection runs a chronic course with
      exacerbations. The bacteria cause local infection destructive to the supporting
      tissues of the teeth and have been detected in systemic diseases through
      bacterial products and bacteria entering the circulation. The often persistent,
      long term history of chronic periodontal infection in individuals is a challenge
      to the immune system. Over 700 oral bacteria and other microorganisms have been
      identified, many of which are virulent. Control of the level of oral microbiota
      is through well known oral hygiene measures. Alcohol by being bactericidal is a
      factor that may reduce the bacterial level in the oral cavity. If this effect
      truly exists, it should be observed through reduction of infections in the mouth.
      Tooth extraction is the ultimate consequence of periodontal and dental infections
      and a reduction of tooth extraction due to infections should therefore be
      observed. The hypothesis was tested using the screening data of the Oslo II-study
      in a cross sectional analysis. The Oslo-study included men aged 48-67 years. The
      main finding was that the effect of a drinking pattern of 2-7 times per week
      reduced the risk of MI among men who had a history of tooth extractions due to
      infections versus tooth extraction for other causes or no extractions. This
      hypothesis supports an explanation as to why oral infection is a weaker
      independent risk factor for CVD in some studies. It also gives an indication of
      the reason for an added benefit by a regular drinking pattern as part of the
      Mediterranean diet. The important consequence of this hypothesis is the added
      importance of optimal oral hygiene for the prevention of CVD as well as for the
      benefit of good oral health.

PMID- 22998954
TI  - Modulation of NGF by cortisol and the Stellate Ganglion Block - is this the
      missing link between memory consolidation and PTSD?
AB  - Post-Traumatic Stress Disorder (PTSD) is a common psychiatric disorder that is
      often associated with intrusive memories and deficits in declarative memory
      function. The neurobiology of this effect is complex. The report focus is to
      provide an overview of systems activated during stress and consequences of the
      activation as well as modulation of those effects. Two systems predominate in
      stress and related memory processing and encoding. They are the autonomic nervous
      system (ANS) and hypothalamic-pituitary-adrenal axis (HPA) axis. ANS has
      significant effect on enhancing encoding of emotional memories, sensitization,
      and fear conditioning with the main neurotransmitter being norepinephrine (NE).
      HPA system is involved in memory regulation where cortisol (CORT), by itself and
      with NE, regulates memories of emotional events. Therapeutic interference with
      stress-related memory dysfunction has been a focus of research for some time. New
      focus of this research may be the HPA axis and ANS. Recent evidence demonstrates
      significant efficacy in prevention of PTSD by administration of CORT, as well as
      treatment of PTSD by utilization of Stellate Ganglion Block (SGB), which reduces
      NE. Both therapeutic approaches may act by a common pathway involving Nerve
      Growth Factor (NGF). This factor may be the "missing link" between memory
      consolidation and PTSD. Suppression of NGF can reduce memory effect directly or
      by effect on NE, leading to prevention or effective treatment of PTSD.

PMID- 22998955
TI  - Behavior analysis: the science of training.
AB  - Behavior analysis is a data-driven science dedicated to understanding the
      mechanisms of behavior. Applied behavior analysis is a branch of this scientific
      field that systematically applies scientific principles to real-world problems in
      an effort to improve quality of life. The use of the behavioral technology
      provides a way to teach human and nonhuman animals more effectively and
      efficiently and offers those using this technology increased success in achieving
      behavioral goals.

PMID- 22998956
TI  - An introduction to the application of science-based training technology.
AB  - Animal training is an applied technology. Its foundation is rooted in the
      principles of behavior analysis. Understanding these principles of learning
      theory can be an important component of successful behavior modification;
      however, true behavior change is the result of practical application. Knowing the
      principles versus applying the technology are two very different skill sets.
      Animal trainers utilize a variety of specific tools, strategies and techniques to
      create a situation in which an animal will successfully learn to present a
      designated behavior. This article discusses the elements and process involved in
      the successful application of behavior change technology to create desired
      behaviors.

PMID- 22998957
TI  - Animal learning and training: implications for animal welfare.
AB  - Exotic animals are housed in a variety of settings, from pets at home, as display
      animals housed in wildlife centers and zoos, to those kept for interactive and
      outreach programs. The behavioral management program and medical care are major
      parts of an excellent animal care program. Because animals learn all the time,
      albeit through different mechanisms, animals are almost always "in training."
      Understanding animal learning when caring for and treating animals can greatly
      improve their welfare during experiences that are often related to involuntary
      procedures and where animals have little control over living conditions or
      procedures.

PMID- 22998958
TI  - A framework for solving behavior problems.
AB  - Applied behavior analysis uses the understanding of behavioral mechanisms to
      manipulate the environment and effect behavior change. Functional assessments
      identify reinforcers maintaining problem behavior using direct and indirect data
      collection strategies. After the function(s) of problem behavior have been
      confirmed or hypotheses have been made, interventions are designed and
      implemented. Behavior change strategies include antecedent interventions and
      training alternative behaviors that serve the same function as the problem
      behavior. Data are collected before, during, and after intervention, and all
      changes in treatment are based on these data.

PMID- 22998959
TI  - Marine mammal training: the history of training animals for medical behaviors and
      keys to their success.
AB  - The training of both domestic and exotic species for participation in medical
      behaviors is a helpful tool in the care and management of individual animals. The
      practice of training individual animals to help in their own health care is
      difficult to trace back to its origins. The use of these techniques on large
      exotic mammals became commonplace only as recently as the late 1990s and early
      2000s. However, the practice seems to have been perfected and made popular with
      marine mammal species, starting in the 1970s. The development of better training
      techniques for a variety of medical behaviors is a foundational key worth
      examining and has been proven to be applicable across species.

PMID- 22998960
TI  - Using operant conditioning and desensitization to facilitate veterinary care with
      captive reptiles.
AB  - In addition to being a large component of most zoological collections, reptile
      species are becoming more popular as family pets. Reptiles have the cognitive
      ability to be trained to facilitate daily husbandry and veterinary care.
      Desensitization and operant conditioning can alleviate some of the behavioral and
      physiological challenges of treating these species. A survey of reptile training
      programs at zoos in the United States and worldwide reveals that there are many
      successful training programs to facilitate veterinary care and minimize stress to
      the animal. Many of the techniques being used to train reptiles in zoological
      settings are transferable to the exotic pet clinician.

PMID- 22998961
TI  - Training techniques to enhance the care and welfare of nonhuman primates.
AB  - Nonhuman primates are excellent subjects for the enhancement of care and welfare
      through training. The application of positive reinforcement techniques to
      specific aspects of the management of captive nonhuman primates spans a wide
      range of species, social contexts, and housing situations (eg, laboratories,
      zoos, and sanctuaries). There is an increased interest from regulatory and
      accrediting agencies to insure improved conditions for captive nonhuman primates,
      apparent by the various standard guidelines, accreditation standards, and
      protocols available for the 3 primary types of nonhuman primate holding
      facilities.

PMID- 22998962
TI  - Training fish and aquatic invertebrates for husbandry and medical behaviors.
AB  - Fishes and aquatic invertebrates are highly diverse groups of animals that are
      well adapted to their aquatic environments. For the past 200 years, researchers
      have been studying the learning potential of fishes and have shown them to be
      extensive. By using these animals' abilities to learn, caretakers can use operant
      conditioning with an emphasis on positive reinforcement to train behaviors aiding
      in dietary management, capture techniques, and medical procedures. Training
      fishes and aquatic invertebrates can help advance the care and well-being of
      these species in human care.

PMID- 22998963
TI  - Small mammal training in the veterinary practice.
AB  - Exotic small mammal patients can experience a great deal of anxiety and fear
      during a visit to a veterinary practice. The stressful experience may continue at
      the client's home during medication routines. The experience is at times so
      stressful to the animal that it damages the relationship of trust with its
      caregiver. This outcome can be changed through the thoughtful use of
      desensitization, counterconditioning, environmental management and positive
      reinforcement training of health care behaviors both in the veterinary practice
      and in the animal's home. Together the veterinarian and the client can create a
      low stress experience.

PMID- 22998964
TI  - Training birds and small mammals for medical behaviors.
AB  - The use of operant conditioning in a zoologic setting allows zookeepers and other
      animal caretakers to train birds and small mammals to participate willingly in
      medical procedures. By using operant conditioning with an emphasis on positive
      reinforcement, small mammals and birds can be trained to cooperate in their own
      medical care in many ways. This conditioning can reduce stress for animals,
      caretakers, and veterinarians as well as reduce the potential for animal
      injuries. This article includes case studies of what the author has identified as
      foundation behaviors, intermediate behaviors, and advanced behaviors and the
      methods used to train them.

PMID- 22998965
TI  - Working raptors and veterinary medicine: preserving the client/veterinarian
      relationship.
AB  - Falconry has a long and rich history of ideas and techniques that have survived
      into modern times, making them time-tested but also antiquated on occasion.
      Working with a raptor in rehabilitation, educational, and, especially, falconry
      situations can be furthered with an understanding of raptor behavior and the
      mindset and specific needs of a raptor keeper. Through understanding birds of
      prey and the requirements of the individuals who keep them, veterinarians can
      both assist in better care for raptors and in preserving relationships with
      raptor-owning clients.

PMID- 22998966
TI  - Teaching avian patients and caregivers in the examination room.
AB  - Client education and patient well-being should be primary goals and
      responsibilities for practicing avian veterinarians. Time is limited in the
      normal clinical appointment setting. However, this opportunity can still be used
      to introduce clients to the basics of training with positive reinforcement. These
      methods build a healthy relationship of trust between caregivers and their birds.
      Within the allotted appointment time, it is possible to teach clients how to
      train a simple behavior. This article outlines and demonstrates how training
      avian patients is successfully applied in a typical clinical practice.

PMID- 22998967
TI  - Technicians and exotic animal training.
AB  - Technicians, whose responsibilities are numerous, play a critical role in a
      veterinary practice. Clients need a trusted source for quality information on
      animal training and behavior that is based on science and noncoercive methods.
      The combination of addressing medical and behavioral needs of exotic animals
      allows a practice to provide added value for their clients. Technicians can play
      an important role in executing many aspects of a successful behavior program.
      From practical application in the examination room for hospitalized patients, to
      helping clients successfully train their animals at home, the end result is a
      cooperative patient and satisfied client.

PMID- 22998968
TI  - Exotic animal training and learning.

PMID- 22998969
TI  - Prevalence of diabetes and predictions of its risks using anthropometric measures
      in southwest rural areas of China.
AB  - BACKGROUND: To examine the prevalence of diabetes and prediabetes in Songming
      county, Yunnan province, South-west China and examine influences of
      anthropometric indicators on diabetic risk. METHODS: This study was a population
      based cross-sectional study of 1031 subjects in Songming County aged 30 years and
      older. Age-standardization was performed by using the 2010 Songming population as
      the standard population. After an overnight fasting, participants underwent an
      oral glucose tolerance test (OGTT), and venous blood glucose levels were measured
      to identify diabetes and prediabetes. Physicians completed questionnaires and
      blood pressure measurements; trained nurses measured anthropometric variables.
      Age-adjusted logistic regression models were used to assess the association
      between anthropometric variables and diabetes. RESULTS: Total prevalences of
      diabetes and prediabetes were 10.0% and 11.6%, respectively. In women, prevalence
      of diabetes and prediabetes significantly increased with body mass index
      (BMI),waist hip ratio (WHR), and waist-to-height ratio (WHtR). But in men,
      prevalence of diabetes and prediabetes only significantly increased with WHR and
      WHtR. Compared to 1st WHR tertile in women, there was a nearly tenfold increase
      in the risk of diabetes with 3rd WHR tertile (OR 10.50, 95% CI 3.95-27.86). Men
      with 3rd BMI tertile had 4.8-fold risk of getting diabetes compared to men with
      1st WHtR tertile (OR 4.79, 95% CI 1.88-12.26). Only WHtR had significantly higher
      receiver operating characteristic (ROC) area than BMI in total men (0.668 vs.
      0.561, p < 0.05). And in total women, only WHR had significantly higher ROC area
      than BMI (0.723 vs. 0.628, p < 0.05). In the partial correlation analysis
      controlling for waist circumference, only WHR had significant correlation with
      fasting plasma glucose (r = 0.132, p = 0.002) and 2-h plasma glucose (r = 0.162,
      p = 0.000) in women, and WHtR had a much stronger association with both fasting
      plasma glucose (r = 0.305, P = 0.000) and 2 h plasma glucose (r = 0.303, P =
      0.000) than WHR in men. CONCLUSION: High prevalence of diabetes and prediabetes
      were found in this underdeveloped region. About half of total subjects with
      diabetes were undiagnosed. The association of obesity indices and diabetic risk
      factors varied with gender. The strongest predictors of diabetes were WHR for the
      female subgroup and WHtR for the male subgroup.

PMID- 22998970
TI  - Clavicle segmentation in chest radiographs.
AB  - Automated delineation of anatomical structures in chest radiographs is difficult
      due to superimposition of multiple structures. In this work an automated
      technique to segment the clavicles in posterior-anterior chest radiographs is
      presented in which three methods are combined. Pixel classification is applied in
      two stages and separately for the interior, the border and the head of the
      clavicle. This is used as input for active shape model segmentation. Finally
      dynamic programming is employed with an optimized cost function that combines
      appearance information of the interior of the clavicle, the border, the head and
      shape information derived from the active shape model. The method is compared
      with a number of previously described methods and with independent human
      observers on a large database. This database contains both normal and abnormal
      images and will be made publicly available. The mean contour distance of the
      proposed method on 249 test images is 1.1+/-1.6mm and the intersection over union
      is 0.86+/-0.10.

PMID- 22998971
TI  - A replication of the study 'Adverse effects of spinal manipulation: a systematic
      review'.
AB  - OBJECTIVE: To assess the significance of adverse events after spinal
      manipulation therapy (SMT) by replicating and critically reviewing a paper
      commonly cited when reviewing adverse events of SMT as reported by Ernst (J Roy
      Soc Med 100:330-338, 2007). METHOD: Replication of a 2007 Ernst paper to compare
      the details recorded in this paper to the original source material. Specific
      items that were assessed included the time lapse between treatment and the
      adverse event, and the recording of other significant risk factors such as
      diabetes, hyperhomocysteinemia, use of oral contraceptive pill, any history of
      hypertension, atherosclerosis and migraine. RESULTS: The review of the 32 papers
      discussed by Ernst found numerous errors or inconsistencies from the original
      case reports and case series. These errors included alteration of the age or sex
      of the patient, and omission or misrepresentation of the long term response of
      the patient to the adverse event. Other errors included incorrectly assigning
      spinal manipulation therapy (SMT) as chiropractic treatment when it had been
      reported in the original paper as delivered by a non-chiropractic provider (e.g.
      Physician).The original case reports often omitted to record the time lapse
      between treatment and the adverse event, and other significant clinical or risk
      factors. The country of origin of the original paper was also overlooked, which
      is significant as chiropractic is not legislated in many countries. In 21 of the
      cases reported by Ernst to be chiropractic treatment, 11 were from countries
      where chiropractic is not legislated. CONCLUSION: The number of errors or
      omissions in the 2007 Ernst paper, reduce the validity of the study and the
      reported conclusions. The omissions of potential risk factors and the timeline
      between the adverse event and SMT could be significant confounding factors.
      Greater care is also needed to distinguish between chiropractors and other health
      practitioners when reviewing the application of SMT and related adverse effects.

PMID- 22998972
TI  - [Gluten-related disorders and demyelinating diseases].
AB  - Gluten-related disorders are a spectrum of systemic immune mediated conditions
      that occur at any age in genetically susceptible individuals upon ingesting
      gluten. Celiac disease and gluten sensitivity are the most important conditions
      of the spectrum. They may be associated with other autoimmune diseases, such as
      multiple sclerosis and neuromyelitis optica. Treatment with a gluten-free diet
      can provide considerable benefits to the patients having both a gluten-related
      disorder and one of these 2 demyelinating diseases of the central nervous system.

PMID- 22998973
TI  - [Plexiform neurofibromas of the sciatic nerve].

PMID- 22998974
TI  - [Orientation of patients referred by their general practionner to the public or
      private hospital sector in France: A prospective epidemiologic study].
AB  - PURPOSE: In-patients characteristics generate cost differences between hospitals.
      In France, there are few data on the characteristics on the patients referred to
      hospitals by their general practitioners (GPs) and none on the predictors of
      referral to the public or for-profit hospitals. The aim of this study was to
      analyze those characteristics and the predictors of referral to the public or for
      profit hospitals. METHODS: We collected, prospectively, the request for
      hospitalizations made by the GPs of the Sentinelles network in France, from 2007
      to 2009. Patients' characteristics and also the reasons for that request were
      analyzed. A logistic regression was used to compare the population between local
      hospitals. RESULTS: Ten thousand seven hundred and eighteen statements were
      collected. The median age was 73 years. Patients were women in 51% of the cases,
      and only 14% of the hospitalizations had been planned. Hospitalization in the
      public sector was preferred for young children and the elderly (P<0.001). When
      compared to the patients referred to the private sector, patients addressed to
      the public sector were more often seen for emergencies (OR: 2.3 [2.0-2.8]), by a
      doctor different from their referring GP (OR: 1.7 [1.4-2.1]) and out of the GP's
      office. The reasons for hospital admission were different depending on the sector
      of hospitalization (P<0.001), patients addressed to the public sector hospitals
      presented with greater comorbidity or more complex diagnosis (for example:
      feeling ill, fainting or syncope and fever) or a greater disability (for example:
      stroke, neurological and psychiatric diseases). CONCLUSION: This study suggests
      that GPs send their patients to the public or for-profit hospitals according to
      criteria of severity, comorbidity and disability.

PMID- 22998975
TI  - [Acquired necrotizing myopathies].
AB  - Necrotizing myopathies (MN) are defined by a specific histological pattern. They
      are characterized by a predominant muscle fibre necrosis and regeneration but
      with little or no associated inflammation. This histological pattern is observed
      in acquired myopathy but also in muscular dystrophy. Acquired NM can be secondary
      to drugs or toxics, and if not, autoimmune mechanisms have to be suspected.
      Necrotizing autoimmune myopathy is recognized as a subgroup of idiopathic
      inflammatory myopathies, different from other myositides. Generally, patients
      present a rapidly progressive and severe symmetrical proximal weakness with high
      serum creatine kinase level, associated in some patients with cardiac
      involvement. On the other hand, a slower progression may sometimes be observed,
      that could lead to erroneous diagnosis of muscular dystrophy. Necrotizing
      autoimmune myopathy may be associated to specific autoantibodies against signal
      recognition particle, or more recently described, against 3-hydroxy-3
      methylglutaryl-coenzyme A reductase. Necrotizing auto-immune myopathy can also be
      described in association with connective tissue diseases such as lupus or
      sclerodermia. In remaining cases, cancer association may be observed. Necrotizing
      autoimmune myopathies are now considered as a new entity, treatable by
      immunosuppressants and which should not be misdiagnosed as a muscular dystrophy.

PMID- 22998976
TI  - [Therapeutic education and internal medicine].
AB  - Therapeutic education is not a recent idea. It arouses renewed interest thanks to
      the article 84 of French law no. 2009-879 from July 21, 2009 reforming the
      hospital and concerning patients, health and territory. This article inserts in
      the public health code no less than five articles devoting patient therapeutic
      education. Nevertheless, the conditions imposed by the legislator raise
      questions, which should be outstripped in favor of a widespread implementation of
      integrated care pathways in which therapeutic education is enclosed. In France,
      internists should be involved in the development of new programs of therapeutic
      education in the field of rare diseases, especially systemic autoimmune diseases.
      A pilot project for systemic lupus erythematosus is ongoing, before an expected
      geographic extension through referent centers, as well as the progressive
      development of additional programs aiming all rare diseases. Content, funding and
      evaluation are key points that remain to be defined.

PMID- 22998977
TI  - [Acquired haemophilia: From registers' data to therapeutic recommendations].

PMID- 22998978
TI  - Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern
      in hypercholesterolemic subjects and its additive effect in patients with
      familial hypercholesterolemia on stable cholesterol-lowering treatment.
AB  - BACKGROUND: Although statins (STs) are drugs of first choice in
      hypercholesterolemic patients, especially in those at high cardiovascular risk,
      some of them are intolerant to STs or refuse treatment with these drugs. In view
      of this, we have evaluated the lipid-lowering effect of a nutraceutical pill
      containing berberine (BBR) and of ezetimibe, as alternative treatments, in
      monotherapy or in combination, in 228 subjects with primary hypercholesterolemia
      (HCH), with history of STs intolerance or refusing STs treatment. In addition,
      since PCSK9 was found up-regulated by STs dampening their effect through an LDL
      receptors (LDLRs) degradation, and BBR suppressed PCSK9 expression in cellular
      studies, we supplemented the stable lipid-lowering therapy of 30 genotype
      confirmed Familial Hypercholesterolemia heterozygotes (HeFH) with BBR, searching
      for a further plasma cholesterol reduction. Plasma lipid pattern was evaluated at
      baseline and during treatments. RESULTS: In HCH subjects the nutraceutical pill
      resulted more effective than EZE in lowering LDL cholesterol (-31.7% vs -25.4%, P
      < 0.001) and better tolerated. On treatment, LDL-C level below 3.36 mmol/L (<=130
      mg/dl) was observed in 28.9% of subjects treated with the nutraceutical pill and
      11.8% of those treated with EZE (P <0.007). In the group treated with EZE the
      subjects carrying the G allele of the g.1679 C > G silent polymorphism of NPC1L1
      gene showed a higher response to EZE than homozygous for the common allele (GG +
      CG: LDL-C -29.4+/-5.0%, CC -23.6+/-6.5%, P <0.001). Combined treatment with these
      drugs was as effective as STs in moderate doses (LDL cholesterol -37%,
      triglycerides -23%). In HeFH patients the addition of BBR resulted in LDL
      cholesterol reductions inversely related to those induced by the stable therapy
      (r = -0.617, P <0.0001), with mean 10.5% further decrease. CONCLUSIONS: The
      alternative treatments tested in our HCH subjects were rather effective and safe.
      The findings in HeFH patients suggest that BBR might act in vivo increasing
      expression and stability of LDLRs and/or suppressing PCSK9 expression.

PMID- 22998979
TI  - Effect of ginseng polysaccharide on the urinary excretion of type 2 diabetic rats
      studied by liquid chromatography-mass spectrometry.
AB  - Ginseng polysaccharide is known to have anti-hyperglycemic and anti
      hyperlipidemic effects in vivo and its precise mechanism of action is not clear.
      A urinary metabolomics method based on rapid-resolution liquid
      chromatography/mass spectrometry (RRLC/MS) was developed to investigate the
      effect of water-soluble ginseng polysaccharide (WGP) on type 2 diabetes in rats.
      Principal component analysis (PCA) was carried out for pattern recognition and a
      clear separation between type 2 diabetic rats and those treated with WGP was
      achieved. Eight potential biomarkers were found and identified. Significantly
      increased inosine, serotonin, phenylpropionylglycine and dodecanedioic acid
      showed the effect of WGP on purine metabolism, tryptophan metabolism, fatty acid
      metabolism and energy metabolism. 1-Methyladenine, 4-deoxyerythronic acid, 5
      hydroxyhexanoic acid and tetrahydrocortisol were significantly decreased which
      indicated that WGP can regulate DNA metabolism, organic acids metabolism and
      steroid hormone metabolism. This work is helpful in the effect mechanism study of
      ginseng polysaccharide.

PMID- 22998980
TI  - Rapid and simultaneous determination of twenty amino acids in complex biological
      and food samples by solid-phase microextraction and gas chromatography-mass
      spectrometry with the aid of experimental design after ethyl chloroformate
      derivatization.
AB  - Amino acids play a vital role as intermediates in many important metabolic
      pathways such as the biosynthesis of nucleotides, vitamins and secondary
      metabolites. A sensitive and rapid analytical method has been proposed for the
      first time for the simultaneous determination of twenty amino acids using solid
      phase microextraction (SPME). The protein samples were hydrolyzed by 6M HCl under
      microwave radiation for 120 min. Then the amino acids were derivatized by ethyl
      chloroformate (ECF) and the ethoxy carbonyl ethyl esters of amino acids formed
      were extracted using SPME by direct immersion. Finally the extracted analytes on
      the SPME fiber were desorbed at 260 degrees C and analyzed by gas chromatography
      mass spectrometer (GC-MS) in electron ionization mode. Factors which affect the
      SPME efficiency were screened by Plackett-Burmann design; most significant
      factors were optimized with response surface methodology. The optimum conditions
      for SPME are as follows: pH of 1.7, ionic strength of 733 mg, extraction time of
      30 min and fiber of divinyl benzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS).
      The recovery of all the amino acids was found to be in the range of 89.17
      100.98%. The limit of detection (LOD) of all derivatized amino acids in urine,
      hair and soybean was found to be in the range of 0.20-7.52 MUg L(-1), 0.21-8.40
      MUg L(-1) and 0.18-5.62 MUg L(-1), respectively. Finally, the proposed technique
      was successfully applied for the determination of amino acids in complex
      biological (hair, urine) and food samples (soybean). The method can find wide
      applications in the routine analysis of amino acids in any biological as well as
      food samples.

PMID- 22998981
TI  - Emergence of novel Leptospira serovars: a need for adjusting vaccination policies
      for dogs?
AB  - A total of 855 sera from dogs in Greece were tested for antibodies to strains
      belonging to the Pomona, Grippotyphosa and Australis serogroups of Leptospira to
      assess exposure levels to these serogroups, possible associations with clinical
      disease and to evaluate whether these findings support the inclusion of
      additional serovars in dog vaccines. Antibodies were detected in 110 (12.9%)
      dogs. The highest seroprevalence (4.9%) was to the proposed novel serovar
      Altodouro belonging to the Pomona serogroup. This serovar also showed a
      statistically significant association with clinical disease. Serovar Bratislava
      antibodies were found in 3.4% of sera. Consideration should be given to the
      inclusion of serovars belonging to the Pomona serogroup and serovar Bratislava in
      future dog vaccines for the Greek market.

PMID- 22998982
TI  - Intradural prostate carcinoma metastatic lesion mimicking an exophytic
      ependymoma: case report.

PMID- 22998984
TI  - Health system reform in the Emirate of Abu Dhabi, United Arab Emirates.
AB  - The desire to achieve the best outcomes in the provision of healthcare has driven
      health system reforms in many countries across the globe, including the Emirate
      of Abu Dhabi, United Arab Emirates. As a young state (the United Arab Emirates
      was founded as an independent state in 1971) with a diverse (with 78%
      expatriates) and young population (40.23% of the national Emirati population is
      under 15 years of age), the government of the Emirate of Abu Dhabi has embarked
      on a journey to reform their healthcare system. This reform focuses on the
      redesign, financing, regulation and provision of healthcare with the aim of
      delivering accessible, affordable and high quality health care. We will describe
      and review the health system reform in Abu Dhabi to date: its background, history
      and characteristics. The review looks at whether the main components of the
      reform (mandatory health insurance; enhanced competition and a centralized
      regulatory system) have had the desired effects in terms of improving quality,
      enhancing access and ensuring affordability. Looking toward the future for the
      health system in Abu Dhabi we conclude that it is too early to tell whether the
      reform programme is having the desired effects in terms of achieving its goals of
      quality, access and affordability.

PMID- 22998983
TI  - Individual Cognitive Stimulation Therapy for dementia (iCST): study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: Improving the quality of care for people with dementia and their
      carers has become a national priority in many countries. Cognitive Stimulation
      Therapy (CST) groups can be beneficial in improving cognition and quality of life
      for people with dementia. The aim of the current study is to develop and evaluate
      a home-based individual Cognitive Stimulation Therapy (iCST) programme for people
      with dementia which can be delivered by their family carer. METHODS: This multi
      centre, pragmatic randomised controlled trial (RCT) will compare the
      effectiveness and cost-effectiveness of iCST for people with dementia with a
      treatment as usual control group. The intervention consists of iCST sessions
      delivered by a carer for 30 minutes, 3 times a week over 25 weeks.For people with
      dementia the primary outcome measures are cognition assessed by the ADAS-Cog, and
      quality of life assessed by QoL-AD. For carers, quality of life using the SF-12
      is the primary outcome measure. Using a 5% significance level, comparison of 306
      participants will yield 80% power to detect an effect size of 0.35 for cognition
      as measured by the ADAS-Cog, and quality of life as measured by the QoL-AD.
      Quality of life for the carer will be measured using the SF-12. The trial will
      include a cost-effectiveness analysis from a public sector perspective.
      DISCUSSION: The UK Department of Health has recently stressed that improving
      access to psychological therapies is a national priority, but many people with
      dementia are unable to access psychological interventions. The development of a
      home-based individual version of CST will provide an easy to use, widely
      available therapy package that will be evaluated for effectiveness and cost
      effectiveness in a multi centre RCT.

PMID- 22998985
TI  - Microbial beta-glucosidases from cow rumen metagenome enhance the
      saccharification of lignocellulose in combination with commercial cellulase
      cocktail.
AB  - BACKGROUND: A complete saccharification of plant polymers is the critical step in
      the efficient production of bio-alcohols. Beta-glucosidases acting in the
      degradation of intermediate gluco-oligosaccharides produced by cellulases limit
      the yield of the final product. RESULTS: In the present work, we have identified
      and then successfully cloned, expressed, purified and characterised 4 highly
      active beta-glucosidases from fibre-adherent microbial community from the cow
      rumen. The enzymes were most active at temperatures 45-55 degrees C and pH 4.0
      7.0 and exhibited high affinity and activity towards synthetic substrates such as
      p-nitrophenyl-beta-D-glucopyranoside (pNPbetaG) and pNP-beta-cellobiose, as well
      as to natural cello-oligosaccharides ranging from cellobiose to cellopentaose.
      The apparent capability of the most active beta-glucosidase, herein named
      LAB25g2, was tested for its ability to improve, at low dosage (31.25 units g-1
      dry biomass, using pNPbetaG as substrate), the hydrolysis of pre-treated corn
      stover (dry matter content of 20%; 350 g glucan kg-1 dry biomass) in combination
      with a beta-glucosidase-deficient commercial Trichoderma reseei cellulase
      cocktail (5 units g-1 dry biomass in the basis of pNPbetaG). LAB25g2 increased
      the final hydrolysis yield by a factor of 20% (44.5 +/- 1.7% vs. 34.5 +/- 1.5% in
      control conditions) after 96-120 h as compared to control reactions in its
      absence or in the presence of other commercial beta-glucosidase preparations. The
      high stability (half-life higher than 5 days at 50 degrees C and pH 5.2) and 2
      38000 fold higher (as compared with reported beta-glucosidases) activity towards
      cello-oligosaccharides may account for its performance in supplementation assays.
      CONCLUSIONS: The results suggest that beta-glucosidases from yet uncultured
      bacteria from animal digestomes may be of a potential interest for
      biotechnological processes related to the effective bio-ethanol production in
      combination with low dosage of commercial cellulases.

PMID- 22998986
TI  - Toxidromes.
AB  - The critical care physician is often called to care for poisoned patients. This
      article reviews the general approach to the poisoned patient, specifically
      focusing on the utility of the toxidrome. A toxidrome is a constellation of
      findings, either from the physical examination or from ancillary testing, which
      may result from any poison. There are numerous toxidromes defined in the medical
      literature. This article focuses on the more common toxidromes described in
      clinical toxicology. Although these toxidromes can aid the clinician in narrowing
      the differential diagnosis, care must be exercised to realize the exceptions and
      limitations associated with each.

PMID- 22998987
TI  - A review of acetaminophen poisoning.
AB  - Acetaminophen poisoning remains one of the more common drugs taken in overdose
      with potentially fatal consequences. Early recognition and prompt treatment with
      N-acetylcysteine can prevent hepatic injury. With acute overdose, the Rumack
      Matthew nomogram is a useful tool to assess risk and guide management. Equally
      common to acute overdose is the repeated use of excessive amounts of
      acetaminophen. Simultaneous ingestion of several different acetaminophen
      containing products may result in excessive dosage. These patients also benefit
      from N-acetylcysteine. Standard courses of N-acetylcysteine may need to be
      extended in patients with persistently elevated plasma concentrations of
      acetaminophen or with signs of hepatic injury.

PMID- 22998988
TI  - Cocaine intoxication.
AB  - Cocaine, a natural alkaloid derived from the coca plant, is one of the most
      commonly abused illicit drugs. Cocaine is commonly abused by inhalation, nasal
      insufflation, and intravenous injection, resulting in many adverse effects that
      ensue from local anesthetic, vasoconstrictive, sympathomimetic, psychoactive, and
      prothrombotic mechanisms. Cocaine can affect all body systems and the clinical
      presentation may primarily result from organ toxicity. Among the most severe
      complications are seizures, hemorrhagic and ischemic strokes, myocardial
      infarction, aortic dissection, rhabdomyolysis, mesenteric ischemia, acute renal
      injury and multiple organ failure.

PMID- 22998989
TI  - Cardiac glycoside toxicity: more than 200 years and counting.
AB  - Digitalis toxicity produces a toxidrome characterized by gastrointestinal,
      neurologic, electrolyte, and nonspecific cardiac manifestations. Chronic toxicity
      remains much more difficult to recognize compared with an acute presentation
      because of the nonspecific manifestations; therefore, serum glycoside levels are
      essential for diagnosis in this population. The mainstay of management continues
      to be rapid toxidrome identification followed by digoxin-specific antibody
      fragment therapy with supportive care. Several controversies still remain,
      including therapy for patients dependent on hemodialysis, appropriateness of
      calcium therapy for hyperkalemia, ideal agents for arrhythmia therapy, and the
      potential utility of plasmapheresis for removal of bound digoxin-antibody
      fragment complexes.

PMID- 22998990
TI  - Carbon monoxide poisoning.
AB  - Carbon monoxide (CO) poisoning is the leading cause of death as a result of
      unintentional poisoning in the United States. CO toxicity is the result of a
      combination of tissue hypoxia-ischemia secondary to carboxyhemoglobin formation
      and direct CO-mediated damage at a cellular level. Presenting symptoms are mostly
      nonspecific and depend on the duration of exposure and levels of CO. Diagnosis is
      made by prompt measurement of carboxyhemoglobin levels. Treatment consists of the
      patient's removal from the source of exposure and the immediate administration of
      100% supplemental oxygen in addition to aggressive supportive measures. The use
      of hyperbaric oxygen is controversial.

PMID- 22998991
TI  - Alcohol withdrawal syndrome.
AB  - In susceptible patients, alcohol withdrawal syndrome (AWS) is often precipitated
      by other medical or surgical disorders, and AWS can adversely affect the course
      of these underlying conditions. Although the mortality rate of AWS has decreased
      over the past few decades, significant risk for morbidity and death remain if
      management is complicated by a variety of conditions. This review of AWS focuses
      on the scope of the clinical problem, historical features, pathophysiology,
      clinical presentation, and approaches to therapy, with particular emphasis on
      severe AWS that requires management in the intensive care unit.

PMID- 22998992
TI  - Miscellaneous central nervous system intoxicants.
AB  - The topic of central nervous system intoxicants encompasses a multitude of
      agents. This article focuses on three classes of therapeutic drugs, with specific
      examples in which overdoses require admission to the intensive care unit.
      Included are some of the newer antidepressants, the atypical neuroleptic agents,
      and selected anticonvulsant drugs. The importance of understanding pertinent
      physiology and applicable supportive care is emphasized.

PMID- 22998993
TI  - Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes.
AB  - Ketoacidotic syndromes are frequently encountered in acute care medicine. This
      article focuses on ketosis and ketoacidotic syndromes associated with
      intoxications, alcohol abuse, starvation, and certain dietary supplements as well
      as inborn errors of metabolism. Although all of these various processes are
      characterized by the accumulation of ketone bodies and metabolic acidosis, there
      are differences in the mechanisms, clinical presentations, and principles of
      therapy for these heterogeneous disorders. Pathophysiologic mechanisms that
      account for these disorders are presented, as well as guidance regarding
      identification and management.

PMID- 22998994
TI  - North American poisonous bites and stings.
AB  - Critters and creatures can strike fear into anyone who thinks about dangerous
      animals. This article focuses on the management of the most common North American
      scorpion, arachnid, hymenoptera, and snake envenomations that cause clinically
      significant problems. Water creatures and less common animal envenomations are
      not covered in this article. Critical care management of envenomed patients can
      be challenging for unfamiliar clinicians. Although the animals are located in
      specific geographic areas, patients envenomed on passenger airliners and those
      who travel to endemic areas may present to health care facilities distant from
      the exposure.

PMID- 22998995
TI  - Methanol and ethylene glycol intoxication.
AB  - Accidental or intentional ingestion of substances containing methanol and
      ethylene glycol can result in death, and some survivors are left with blindness,
      renal dysfunction, and chronic brain injury. However, even in large ingestions, a
      favorable outcome is possible if the patient arrives at the hospital early enough
      and the poisoning is identified and appropriately treated in a timely manner.
      This review covers the common circumstances of exposure, the involved toxic
      mechanisms, and the clinical manifestations, laboratory findings, and treatment
      of methanol and ethylene glycol intoxication.

PMID- 22998996
TI  - Toxicology.

PMID- 22998997
TI  - Efficacy and safety of anidulafungin in elderly, critically ill patients with
      invasive Candida infections: a post hoc analysis.
AB  - Post hoc analysis of a non-comparative, prospective, multicentre, phase IIIb
      study was performed to compare efficacy and safety of anidulafungin in elderly
      (>=65 years) versus non-elderly (<65 years) Intensive Care Unit (ICU) patients
      with candidaemia/invasive candidiasis (C/IC). Adult ICU patients with confirmed
      C/IC meeting >=1 of the following criteria were enrolled: post-abdominal surgery;
      solid tumour; renal/hepatic insufficiency; solid organ transplantation;
      neutropenia; age >=65 years. Patients received anidulafungin (200 mg on Day 1,
      100 mg/day thereafter) for >=10 days followed by optional azole step-down therapy
      for a total treatment duration of 14-56 days. The primary efficacy endpoint was
      global (clinical and microbiological) response at the end of all therapy (EOT).
      Primary efficacy analysis was performed in the modified intent-to-treat (mITT)
      population (n=170), excluding unknown and missing responses. In total, 80
      patients (47.1%) were aged >=65 years and 90 (52.9%) were aged <65 years; the
      mean age difference between the two groups was 21.9 years. Global success at EOT
      in mITT patients was similar in elderly (68.1%) and non-elderly (70.7%) patients
      (P=0.719). However, global success rates were significantly lower in elderly
      versus non-elderly patients at 2 and 6 weeks after EOT (P=0.045 and P=0.016,
      respectively). Ninety-day survival was significantly lower (P=0.006) for elderly
      (42.8%) versus non-elderly patients (63.3%). The incidence and profile of adverse
      events were similar in elderly and non-elderly patients. Anidulafungin was
      effective and safe for treatment of C/IC in elderly ICU patients, despite higher
      baseline severity of illness scores.

PMID- 22998998
TI  - Histopathological and biological studies of the effect of cadmium on Rhinella
      arenarum gonads.
AB  - This study was to determine the lethal dose 50 (LD(50)) of CdCl(2) in adult
      Rhinella arenarum and analyzed the effect of two sublethal doses (0.5 and 5
      mg/kg) of the xenobiotic in gonads. The 48 h LD(50) were 50.0 and 49.8 mg/kg for
      males and females respectively. Alterations in the ovary were evidenced by
      nuclear pleomorphism and cytoplasmic vacuolization of the oocytes at the early
      stages of development with the highest dose and an increase in the population of
      atretic oocytes. In the interstitial tissue we noticed congestion, edema and
      fibroblast proliferation. The nuclear maturation of the oocytes was affected by
      the xenobiotic in a dose- and time-dependent manner. In males, treatment with 5
      mg/kg of cadmium (Cd) caused a decrease in the concentration, viability and
      straight progressive motility of sperm while there was an increase in immotile
      sperm. Testis histopathology revealed dilated seminiferous tubules, disappearance
      of cysts, tissue disorganization and leukocyte infiltration. Numerous germ cells
      showed hydropic tumefaction or signs of focal necrosis. The Cd content in animals
      intoxicated gonads with the highest sublethal dose was significantly higher than
      in the control. Results indicate that R. arenarum gonads are target for the
      xenobiotic, compromising the formation of gametes competent for fertilization,
      the effective CdCl(2) dose being 5 mg/kg.

PMID- 22998999
TI  - Effect of cottonseed oilcake inclusion on ostrich growth performance and meat
      chemical composition.
AB  - This study investigated the effect of replacing dietary soybean oilcake meal with
      increasing levels of cottonseed oilcake meal (CSOCM) on the growth performance
      and meat (Iliofibularis muscle) chemical composition of ostriches in order to
      decrease total feed costs. A total of 105 ostriches were divided into five
      feeding groups according to the CSOCM inclusion level in the whole diet: Control
      (0% CSOCM), 3%, 6%, 9% and 12% CSOCM (of the whole diet), and fed with
      experimental diets from 6 to 13 months of age. As a result of feeding CSOCM, the
      final live weight and the average daily gain significantly increased in the 12%
      CSOCM group. The proximate composition, cholesterol content, mineral and fatty
      acid profile of the meat remained unaffected. Thus CSOCM may be used as an
      alternative protein source to the more expensive soybean oilcake meal in ostrich
      nutrition.

PMID- 22999000
TI  - SmartStretchTM technology. III. The impact of medium voltage stimulation and
      SmartStretchTM technology on sheep topside (m. semimembranosus) meat quality
      traits under commercial processing conditions.
AB  - This study evaluated the interaction between medium voltage electrical
      stimulation, SmartStretchTM stretching and ageing treatments on key meat quality
      traits of hot boned sheep m. semimembranosus. Medium voltage stimulation reduced
      initial pH (P<0.001), but did not impact on other meat quality traits. There was
      a significant interaction between stretch treatment and ageing (P<0.001) for
      shear force such that samples which were both stretched and aged were the most
      tender. Sarcomere length was significantly (P<0.001) increased by SmartStretchTM
      treatment. Control (no stretching) resulted in greater (P<0.05) cooking loss, but
      there was significantly less purge loss (P<0.05). The ratio 630/580 nm and a*
      colour values at 0 and 5 days decreased at a significantly (P<0.05) slower rate
      when SmartStretchTM was applied. Overall medium voltage stimulation did not
      inhibit the effectiveness of the SmartStretchTM treatment. The SmartStretchTM
      treatment provided significant improvement in tenderness and the potential to
      increase meat display time.

PMID- 22999001
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is
      an increasingly used technique by the interventional pulmonologist in lung cancer
      staging and diagnosis of both malignant and benign mediastinal lymphadenopathy
      amongst other applications. There are increasing data to support the use of EBUS
      TBNA over mediastinoscopy as a first staging or diagnostic procedure in defined
      situations. In this review, the technique of EBUS-TBNA is briefly discussed with
      a more extended discussion around comparative studies of mediastinal staging
      techniques, with an emphasis on the recent ASTER trial as well as impending
      trials and diagnostic performance studies of EBUS-TBNA in sarcoidosis.

PMID- 22999003
TI  - Chemical matricectomy with phenol.

PMID- 22999004
TI  - Physiological relevance and performance of a minimal lung model: an experimental
      study in healthy and acute respiratory distress syndrome model piglets.
AB  - BACKGROUND: Mechanical ventilation (MV) is the primary form of support for acute
      respiratory distress syndrome (ARDS) patients. However, intra- and inter- patient
      variability reduce the efficacy of general protocols. Model-based approaches to
      guide MV can be patient-specific. A physiological relevant minimal model and its
      patient-specific performance are tested to see if it meets this objective above.
      METHODS: Healthy anesthetized piglets weighing 24.0 kg [IQR: 21.0-29.6] underwent
      a step-wise PEEP increase manoeuvre from 5cmH2O to 20cmH2O. They were ventilated
      under volume control using Engstrom Care Station (Datex, General Electric,
      Finland), with pressure, flow and volume profiles recorded. ARDS was then induced
      using oleic acid. The data were analyzed with a Minimal Model that identifies
      patient-specific mean threshold opening and closing pressure (TOP and TCP), and
      standard deviation (SD) of these TOP and TCP distributions. The trial and use of
      data were approved by the Ethics Committee of the Medical Faculty of the
      University of Liege, Belgium. RESULTS AND DISCUSSIONS: 3 of the 9 healthy piglets
      developed ARDS, and these data sets were included in this study. Model fitting
      error during inflation and deflation, in healthy or ARDS state is less than 5.0%
      across all subjects, indicating that the model captures the fundamental lung
      mechanics during PEEP increase. Mean TOP was 42.4cmH2O [IQR: 38.2-44.6] at PEEP =
      5cmH2O and decreased with PEEP to 25.0cmH2O [IQR: 21.5-27.1] at PEEP = 20cmH2O.
      In contrast, TCP sees a reverse trend, increasing from 10.2cmH2O [IQR: 9.0-10.4]
      to 19.5cmH2O [IQR: 19.0-19.7]. Mean TOP increased from average 21.2-37.4cmH2O to
      30.4-55.2cmH2O between healthy and ARDS subjects, reflecting the higher pressure
      required to recruit collapsed alveoli. Mean TCP was effectively unchanged.
      CONCLUSION: The minimal model is capable of capturing physiologically relevant
      TOP, TCP and SD of both healthy and ARDS lungs. The model is able to track
      disease progression and the response to treatment.

PMID- 22999005
TI  - Poor seroprotection but allosensitization after adjuvanted pandemic influenza
      H1N1 vaccine in kidney transplant recipients.
AB  - BACKGROUND: Seasonal and pandemic influenza virus infections in renal transplant
      patients are associated with poor outcomes. During the pandemic of 2009-2010, the
      AS03-adjuvanted monovalent H1N1 influenza vaccine was recommended for transplant
      recipients, although its immunogenicity in this population was unknown. We sought
      to determine the safety and immunogenicity of an adjuvant-containing vaccine
      against pandemic influenza A H1N1 2009 (pH1N1) administered to kidney transplant
      recipients. METHODS: We prospectively enrolled 124 adult kidney transplant
      recipients in the fall of 2009 at two transplant centers. Cohort 1 (n = 42) was
      assessed before and after pH1N1 immunization, while Cohort 2 (n = 82) was only
      assessed post immunization. Humoral response was measured by the hemagglutination
      inhibition assay. Vaccine safety was assessed by adverse event reporting, graft
      function, and human leukocyte antigen (HLA) alloantibody measurements. RESULTS:
      Cohort 1 had a low rate of baseline seroprotection to pH1N1 (7%) and a low rate
      of seroprotection after immunization (31%). No patient <6 months post transplant
      (n = 5) achieved seroprotection. Seroprotection rate was greater in patients
      receiving double as compared with triple immunosuppression (80% vs. 24%, P =
      0.01). In Cohort 2, post-immunization seroprotection was 35%. In both cohorts, no
      confirmed cases of pH1N1 infection occurred. No difference was seen in estimated
      glomerular filtration rate before (54.3 mL/min/1.73 m(2) ) and after (53.8
      mL/min/1.73 m(2) ) immunization, and no acute rejections had occurred after
      immunization at last follow-up. In Cohort 1, 11.9% of patients developed new anti
      HLA antibodies. CONCLUSION: An adjuvant-containing vaccine to pH1N1 provided poor
      seroprotection in renal transplant recipients. Receiving triple immunosuppression
      was associated with a poor seroresponse. Vaccination appeared safe, but some
      patients developed new anti-HLA antibodies post vaccination. Alternative
      strategies to improve vaccine responses are necessary.

PMID- 22999006
TI  - [Social networks and impact factor of medical journals].

PMID- 22999007
TI  - CeO2 surface oxygen vacancy concentration governs in situ free radical scavenging
      efficacy in polymer electrolytes.
AB  - Nonstoichiometric CeO(2) and Ce(0.25)Zr(0.75)O(2) nanoparticles with varying
      surface concentrations of Ce(3+) were synthesized. Their surface Ce(3+)
      concentration was measured by XPS, and their surface oxygen vacancy
      concentrations and grain size were estimated using Raman spectroscopy. The
      surface oxygen vacancy concentration was found to correlate well with grain size
      and surface Ce(3+) concentration. When incorporated into a Nafion polymer
      electrolyte membrane (PEM), the added nonstoichiometric ceria nanoparticles
      effectively scavenged PEM-degradation-inducing free radical reactive oxygen
      species (ROS) formed during fuel cell operation. A 3-fold increase in the surface
      oxygen vacancy concentration resulted in an order of magnitude enhancement in the
      efficacy of free radical ROS scavenging by the nanoparticles. Overall, the
      macroscopic PEM degradation mitigation rate was lowered by up to 2 orders of
      magnitude using nonstoichiometric ceria nanoparticles with high surface oxygen
      vacancy concentrations.

PMID- 22999008
TI  - From redefined hypotension to optimal cerebral blood flow in traumatic brain
      injury: let's use transcranial Doppler.

PMID- 22999010
TI  - Personalized oncology: recent advances and future challenges.
AB  - Personalized oncology is evidence-based, individualized medicine that delivers
      the right care to the right cancer patient at the right time and results in
      measurable improvements in outcomes and a reduction on health care costs.
      Evolving topics in personalized oncology such as genomic analysis, targeted
      drugs, cancer therapeutics and molecular diagnostics will be discussed in this
      review. Biomarkers and molecular individualized medicine are replacing the
      traditional "one size fits all" medicine. In the next decade the treatment of
      cancer will move from a reactive to a proactive discipline. The essence of
      personalized oncology lies in the use of biomarkers. These biomarkers can be from
      tissue, serum, urine or imaging and must be validated. Personalized oncology
      based on biomarkers is already having a remarkable impact. Three different types
      of biomarkers are of particular importance: predictive, prognostic and early
      response biomarkers. Tools for implementing preemptive medicine based on genetic
      and molecular diagnostic and interventions will improve cancer prevention.
      Imaging technologies such as Computed Tomography (CT) and Positron Emitted
      Tomography (PET) are already influencing the early detection and management of
      the cancer patient. Future advances in imaging are expected to be in the field of
      molecular imaging, integrated diagnostics, biology driven interventional
      radiology and theranostics. Molecular diagnostics identify individual cancer
      patients who are more likely to respond positively to targeted chemotherapies.
      Molecular diagnostics include testing for genes, gene expression, proteins and
      metabolites. The use of companion molecular diagnostics is expected to grow
      significantly in the future and will be integrated into new cancer therapies a
      single (bundled) package which will provide greater efficiency, value and cost
      savings. This approach represents a unique opportunity for integration, increased
      value in personalized oncology.

PMID- 22999011
TI  - In patients with non-alcoholic fatty liver disease, metabolically abnormal
      individuals are at a higher risk for mortality while metabolically normal
      individuals are not.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common cause
      of chronic liver disease and is strongly associated with metabolic syndrome. The
      aim of this study is to compare the clinical profile and long-term outcome in
      NAFLD patients with or without metabolic syndrome. METHODS: The initial cohort
      (N=6709) was identified from National Health and Nutrition Examination Survey-III
      (NHANES III, 1988-94) data. Laboratory profiles, body measurement examinations,
      and mortality data were linked to self-reported questionnaires of demographic and
      health risk information. NAFLD was defined as significant steatosis on hepatic
      ultrasound after exclusion of other chronic liver diseases (N=1448). NAFLD
      patients were classified according to presence or absence of metabolic syndrome.
      Mortality was determined through December 31, 2006. Cox models were used to
      estimate hazard ratios and 95% confidence intervals for all-cause, cardiovascular
      and liver-specific mortality differences between two sub-cohorts of NAFLD with
      and without metabolic syndrome. RESULTS: NAFLD participants with metabolic
      syndrome were more likely to be Non-Hispanic white, older, and have higher
      aminotransferase levels. All-cause mortality (P<.001) and cardiovascular
      mortality (P<.001) were higher in NAFLD patients with metabolic syndrome.
      Furthermore, the presence of metabolic syndrome was independently associated with
      overall mortality, liver-specific mortality, and cardiovascular mortality. Age
      was an independent predictor of both all-cause and cardiovascular mortality.
      Elevated liver enzymes and obesity were two other independent predictors of liver
      specific mortality. There were no differences in all-cause, liver-related, or
      cardiovascular mortality between groups of individuals without liver disease and
      individuals with NAFLD without metabolic syndrome (metabolically-normal).
      CONCLUSIONS: Diagnosis of NAFLD with metabolic syndrome is an independent
      predictor of all-cause, liver-specific, and cardiovascular mortality. In
      contrast, mortality of metabolically-normal NAFLD patients is similar to the
      cohort without liver disease.

PMID- 22999014
TI  - Salmonella in meats, water, fruit and vegetables as disclosed from testing
      undertaken by Food Business Operators in Ireland from 2005 to 2009.
AB  - Food Business Operators (FBO) are responsible for the safety of the food they
      produce and in Ireland those under the regulatory control of the Department of
      Agriculture, Food and Marine are required to provide summary data on
      microbiological tests undertaken as part of their food safety controls. These
      data are provided to the National Reference Laboratory through the 25 private
      laboratories undertaking the testing. RESULTS: Over the five-year period
      Salmonella sp. was isolated from 0.7% of the 254,000 raw meat or raw meat
      products tested with the annual prevalence ranging from 0.5 to 1.1%. Poultry
      meats were consistently more contaminated than other meats with higher recovery
      rates in turkey (3.3%), duck (3.3%), and chicken (2.5%) compared with meats of
      porcine (1.6%), ovine (0.2%) and bovine origin (0.1%). Salmonella sp. was also
      isolated from 58 (0.06%) of the 96,115 cooked or partially cooked meat and meat
      products tested during the reporting period with the annual percentage positive
      samples ranging from 0.01 to 0.16%. A total of 50 different serotypes were
      recovered from raw meats over this period with the greatest diversity found in
      poultry samples (n = 36). Four serotypes, Kentucky, Typhimurium, Agona and Derby
      accounted for over 70% of all isolates detected on FBO testing over the period
      2005 to 2009. CONCLUSIONS: Capturing microbiological data generated by Food
      Business Operators allows the regulatory sector access to a substantial amount of
      valuable data with the minimum financial outlay.

PMID- 22999012
TI  - Peripheral fat loss and decline in adipogenesis in older humans.
AB  - OBJECTIVE: Aging is associated with a redistribution of body fat including a
      relative loss of subcutaneous peripheral fat. These changes in body fat can have
      important clinical consequences since they are linked to increased risk of
      metabolic complications. The causes and mechanisms of loss of peripheral fat
      associated with aging are not clear. The aim of this study was to assess whether
      defects in adipogenesis contribute to fat loss in aging humans, as suggested from
      animal studies, and to evaluate the role of inflammation on pathogenesis of fat
      loss. MATERIALS/METHODS: Preadipocytes isolated from subcutaneous peripheral fat
      of healthy young and elderly subjects were compared in their ability to replicate
      and differentiate. RESULTS: The results show that both the rate of replication
      and differentiation of preadipocytes are reduced in older subjects. The reduction
      in adipogenesis is accompanied by a higher plasma level of the inflammatory
      marker, soluble tumor necrosis factor receptor 2, and greater release of tumor
      necrosis factor alpha from fat tissue. CONCLUSIONS: Thus, the gradual relative
      loss of peripheral fat in aging humans may in part result from a defect in
      adipogenesis, which may be linked to inflammation and increased release of
      proinflammatory cytokines from fat tissue.

PMID- 22999015
TI  - A mouse model for too much TV?
AB  - In a new study published in Scientific Reports, Christakis and colleagues
      investigate a mouse model for technology-induced overstimulation. We review their
      findings, discuss the challenges of defining overstimulation, and consider the
      resemblance of the phenotypes observed in Christakis et al. to those noted in
      genetic models of attention deficit hyperactivity disorder (ADHD).

PMID- 22999017
TI  - A theoretical framework for early human studies: uncertainty, intervention
      ensembles, and boundaries.
AB  - Clinical development of novel therapeutics begins with a coordinated sequence of
      early phase clinical trials. Such early human studies confront a series of
      methodological and ethical challenges. In what follows, I propose a theoretical
      framework for early human studies aimed at informing the negotiation of these
      challenges. At the outset of clinical development, researchers confront a
      virtually undifferentiated landscape of uncertainty with respect to three
      variables: outcomes, their probability of occurrence, and operation dimensions
      needed to effectuate favorable outcomes. Early human trials transform this
      uncertain landscape into one where there are grounds for belief about risk and
      benefit for various combined operation dimensions. To accomplish this, studies
      set out with two aims. First, they identify a set of operation dimensions that,
      when combined as a package (intervention ensemble), elicits a reasonable
      probability of a target outcome. Second, they define the boundaries of dimension
      values within an intervention ensemble. This latter aim entails exposing at least
      some volunteers in early studies to treatments that are inactive or excessive. I
      provide examples that illustrate the way early human studies discover and delimit
      intervention ensembles, and close by offering some implications of this framework
      for ethics, methodology, and efficiency in clinical development of new
      interventions.

PMID- 22999016
TI  - Panic attack triggering myocardial ischemia documented by myocardial perfusion
      imaging study. A case report.
AB  - BACKGROUND: Chest pain, a key element in the investigation of coronary artery
      disease is often regarded as a benign prognosis when present in panic attacks.
      However, panic disorder has been suggested as an independent risk factor for long
      term prognosis of cardiovascular diseases and a trigger of acute myocardial
      infarction. OBJECTIVE: Faced with the extreme importance in differentiate from
      ischemic to non-ischemic chest pain, we report a case of panic attack induced by
      inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by
      myocardial perfusion imaging study. DISCUSSION: Panic attack is undoubtedly a
      strong component of mental stress. Patients with coronary artery disease may
      present myocardial ischemia in mental stress response by two ways: an increase in
      coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in
      myocardial oxygen consumption. Coronary artery spasm was presumed to be present
      in cases of cardiac ischemia linked to panic disorder. Possibly the carbon
      dioxide challenge test could trigger myocardial ischemia by the same mechanisms.
      CONCLUSION: The use of mental stress has been suggested as an alternative method
      for myocardial ischemia investigation. Based on translational medicine objectives
      the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to
      allow improved application of research-based knowledge to the medical field,
      specifically at the interface of PD and cardiovascular disease.

PMID- 22999018
TI  - Two novel indices for quantitatively characterizing the toxicity interaction
      between ionic liquid and carbamate pesticides.
AB  - Compound contamination and toxicity interaction demand the development of models
      that have an insight into the combined toxicity of chemicals. Two novel mixture
      toxicity indices, concentration addition index (CAI) and effect addition index
      (EAI), were developed to quantitatively characterize the toxicity interaction
      within four binary mixture systems containing carbamate pesticides and 1-benzyl-3
      methylimidazolium tetrafluoroborate (IL). To examine the applicability of CAI and
      EAI, we compared the indices with the other indices such as the sum of toxic unit
      (STU), model deviation ratio (MDR), and effect residual ratio (ERR) and
      isobologram approach. The results showed that CAI and EAI could more clearly and
      effectively characterize the toxicity interaction within IL-pesticide mixtures
      than the other four methods. According to CAI and EAI, IL-aldicarb, IL-baygon and
      IL-methomyl mixture systems displayed clear antagonism at relatively low effect
      regions, while IL-pirimicarb mixture systems basically exhibited additive action.
      The most interesting observation is that all five indices (CAI, EAI, MDR, ERR,
      and STU) are well correlated with the concentration ratio of IL in the mixtures.

PMID- 22999019
TI  - Arsenic mobilization in the aquifers of three physiographic settings of West
      Bengal, India: understanding geogenic and anthropogenic influences.
AB  - A comparative hydrogeochemical study was carried out in West Bengal, India
      covering three physiographic regions, Debagram and Chakdaha located in the
      Bhagirathi-Hooghly alluvial plain and Baruipur in the delta front, to demonstrate
      the control of geogenic and anthropogenic influences on groundwater arsenic (As)
      mobilization. Groundwater samples (n = 90) from tube wells were analyzed for
      different physico-chemical parameters. The low redox potential (Eh = -185 to -86
      mV) and dominant As(III) and Fe(II) concentrations are indicative of anoxic
      nature of the aquifer. The shallow (<100 m) and deeper (>100 m) aquifers of
      Bhagirathi-Hooghly alluvial plains as well as shallow aquifers of delta front are
      characterized by Ca(2+)HCO3(-) type water, whereas Na(+) and Cl(-) enrichment is
      found in the deeper aquifer of delta front. The equilibrium of groundwater with
      respect to carbonate minerals and their precipitation/dissolution seems to be
      controlling the overall groundwater chemistry. The low SO4(2-) and high DOC,
      PO4(3-) and HCO3(-) concentrations in groundwater signify ongoing microbial
      mediated redox processes favoring As mobilization in the aquifer. The As release
      is influenced by both geogenic (i.e. geomorphology) and anthropogenic (i.e.
      unsewered sanitation) processes. Multiple geochemical processes, e.g., Fe
      oxyhydroxides reduction and carbonate dissolution, are responsible for high As
      occurrence in groundwaters.

PMID- 22999020
TI  - Proteome pattern in oysters as a diagnostic tool for metal pollution.
AB  - The present study investigated whether proteome pattern of an oyster Crassostrea
      hongkongensis could be used as a diagnostic tool for contamination and toxicity
      of metals/metalloids in a real multiple metal-contaminated estuary. We collected
      oysters along a pollution gradient from highly contaminated to relatively clean
      sites. The oysters showed distinct contamination gradients of Cu, Zn and Cd.
      Proteomic analysis of the oyster gills as one of major metal targets identified a
      proteome pattern composed of 13 commonly altered proteins in the contaminated
      oysters. The discovered proteome pattern completely segregated the contaminated
      from the clean individuals, and the pattern achieved clear classification of the
      oysters with different contamination levels. Importantly, the integrated changes
      of gill proteome were linearly related to the integrated contamination of the
      metal mixtures present in oyster tissues. It is suggested that proteome pattern
      is a promising diagnostic tool for metal pollution assessment in environmental
      monitoring programs.

PMID- 22999021
TI  - Student-faculty trust and student success in pre-licensure baccalaureate nurse
      education.
AB  - OBJECTIVE: Nurse educators need an enhanced understanding of factors contributing
      to nursing student success to decrease attrition and increase retention. Improved
      understanding of factors related to successful nurse preparation could improve
      educational processes and facilitate student success, thereby addressing the
      worldwide nursing shortage as well as increasing the competence and expertise of
      new graduates. Student-faculty trust and related characteristics have been
      identified as factors associated with student success (Applebaum, 1995). Research
      investigating trust in communications and education has been conducted with
      students in other disciplines but not with nursing students. This research
      investigated the complex relationships between students' trust in faculty, the
      students' mood states, and students' educational performance and outcomes.
      METHOD: The study utilized a quantitative, cross-sectional, descriptive, and
      correlational design. Student volunteers were recruited from a baccalaureate
      nursing education program located in the southwest United States. Participants
      completed three instruments: the Health Sciences Reasoning Test (HSRT), Profile
      of Mood States (POMS), and Interpersonal Trust Scale (ITS). The resulting scores
      were compared and contrasted along with selected demographic variables. RESULTS:
      The study identified a significant relationship between total mood disturbance
      and interpersonal trust. The trends in the POMS subscales of Anger and Confusion
      are of particular interest, as the two factors strongly influenced shifts in
      Total Mood Disturbance. As students progressed through the nursing program,
      experiences of Anger and Confusion increased with each progressive semester and
      were accompanied by corresponding decreases in trust. CONCLUSIONS: The results
      complement established findings relating mood and cognitive function. Alterations
      in the student's level of trust potentially could share relationships with
      cognition and critical thinking, although perhaps not in a direct and linear
      fashion.

PMID- 22999022
TI  - The 'good' apprentice-revisiting Irish nursing's coming of age.

PMID- 22999023
TI  - "What are nurse academics for?" Intellectual craftsmanship in an age of
      instrumentalism.

PMID- 22999024
TI  - Prevalence of antibodies against measles, mumps and rubella in the childhood
      population in Singapore, 2008-2010.
AB  - We undertook a national paediatric seroprevalence survey of measles, mumps and
      rubella (MMR) in Singapore to assess the impact of the national childhood
      immunization programme against these three diseases after introduction of the
      trivalent MMR vaccine in 1990. The survey involved 1200 residual sera of
      Singapore residents aged 1-17 years collected from two hospitals between 2008 and
      2010. The overall prevalence of antibodies against measles, mumps and rubella was
      83?1% [95% confidence interval (CI) 80?9-85?1], 71.8% (95% CI 69?1-74?2) and
      88?5% (95% CI 86?6-90?2), respectively. For all three diseases, the lowest
      prevalence was in children aged 1 year (47?8-62?3%). The seroprevalence of the
      vaccinated children declined over time. The national MMR immunization programme
      is effective in raising the herd immunity of the childhood population, although
      certain age groups are more susceptible to infection, in particular, those who
      are not eligible for vaccination at age <15 months.

PMID- 22999026
TI  - Clinical pharmacology for the primary care physician.

PMID- 22999009
TI  - Bias towards dementia: are hip fracture trials excluding too many patients? A
      systematic review.
AB  - Patients with hip fractures are older and often present many co-morbidities,
      including dementia. These patients cannot answer quality of life questionnaires
      and are generally excluded from trials. We hypothesized that a significant number
      of patients are being excluded from these studies and this may impact outcomes.
      This was a two part study; the first analyzing databases of two ongoing large
      scale multi-centred hip fracture trials and the second being a systematic review.
      The FAITH and HEALTH studies were analyzed for exclusion incidence directly
      related to dementia. The second part consisted of a systematic search of all
      relevant studies within the last 20 years. In the FAITH study, a total of 1690
      subjects were excluded, 375 (22.2%) of which were due to dementia or cognitive
      impairment. In the HEALTH study, 575 were excluded with dementia/cognitive
      impairment representing 207 patients (36%). Following the systematic review, 251
      articles were identified 17 of which were retained. The overall prevalence of
      dementia was 27.9% (range 2-51%). Only two studies compared demented and non
      demented groups. In these studies significant increases in both mortality and
      complications were found. In summary, when investigating hip fractures, choosing
      appropriate objective endpoints is essential to ensure results are also
      applicable to patients with dementia.

PMID- 22999028
TI  - Taking charge of our future: curricular approaches to improve quality and safety
      in psychiatric nursing practice and health care.

PMID- 22999027
TI  - Tophi and frequent gout flares are associated with impairments to quality of
      life, productivity, and increased healthcare resource use: Results from a cross
      sectional survey.
AB  - BACKGROUND: The prevalence of gout is increasing, and most research on the
      associated burden has focused on serum urate (sUA) levels. The present study
      quantifies the impact of the presence of tophi and frequency of acute gout
      attacks on health-related quality of life (HRQOL), productivity, and healthcare
      resource utilization. METHODS: Patients with self-reported gout (n=620; 338 in US
      and 282 across France, Germany, and UK) were contacted based on inclusion in the
      2010 US and EU National Health and Wellness Surveys (Kantar Health) and the
      Lightspeed Research ailment panel. Respondents were categorized into mutually
      exclusive groups based on number of gout flares experienced in the past 12 months
      (0/don't recall, 1-2, 3, 4-5, 6+), current presence of tophi (none, 1+, or not
      sure), and sUA level awareness (yes, no). HRQOL (SF-12v2), healthcare provider
      visits in the last 6 months, and work productivity and activity impairment (WPAI)
      were compared across groups. RESULTS: Most patients were males, mean age of 61
      years, who reported experiencing at least one acute gout flare in the past 12
      months, and 12.3% (n=76) reported presence of tophi. Among the 27.7% (n=172) of
      patients who were aware of their sUA levels, higher sUA was associated with more
      flares and tophi. Decreased HRQOL was associated with more frequent flares and
      presence of tophi. In multivariable models predicting outcomes based on presence
      of tophi and number of flares, both flares (>=4) and tophi (>=1) were associated
      with HRQOL decrements on physical and mental component summary scores and health
      utilities (all p<0.05), after adjustment for age, gender, and time since
      diagnosis. Flares were also associated with greater activity impairment.
      CONCLUSIONS: Impairments associated with gout flares and presence of tophi,
      across patients in the US and EU, underscore the importance of effective
      management of this potentially curable condition.

PMID- 22999029
TI  - Developing a reflection-centered curriculum for graduate psychiatric nursing
      education.
AB  - This article discusses theoretical underpinnings, teaching strategies, and
      preliminary evaluation relative to the development of a reflective curriculum
      used in our distance-accessible graduate psychiatric nursing program. Influenced
      by the collective ideas of J. Dewey (1993), J. Reed and S. Proctor (1993), D. A.
      Kolbe (1984), J. Mezirow (1981), C. Johns (2006), D. Schon (1983), D. Freshwater
      (2008), and others who have promoted reflection as a transformative teaching and
      learning process, we sought to develop a curriculum that balanced knowledge and
      skill acquisition with critical reflective practices that would instill habits of
      lifelong learning. We began with traditional approaches to psychiatric nursing
      education, including case study analysis and modified lectures that we call mini
      lectures. We then added principles and practices of reflection to allow for
      merging these traditional approaches with contemporary reflection-focused
      approaches. Specific ways to use reflection in a graduate psychiatric nursing
      curriculum are described to demonstrate how we have taken our curriculum beyond
      traditional ways of teaching and learning toward one that emphasizes building
      knowledge and skill through reflective practice.

PMID- 22999030
TI  - Quality and safety graduate competencies in psychiatric mental health nurse
      practitioner education.
AB  - Education of the psychiatric mental health nurse practitioner (PMHNP) is
      undergoing massive change, partially driven by practice requirements and national
      certification changes, the development of new nurse practitioner competencies,
      and the development of the graduate quality and safety in nursing (QSEN)
      competencies. We are in the middle of a paradigm shift of expectations, not only
      just from these new competencies but also from the context of care and the impact
      PMHNP graduates will have on policy and health care delivery in the future. In
      this review article, the authors will discuss the general categories of the
      graduate QSEN competencies and how they relate to PMHNP education, competency
      development, and the application to curricular development in PMHNP programs
      across the United States. Importantly, these changes into PMHNP education, while
      remaining true to the fundamental tenants of advanced practice psychiatric
      nursing, prepare the PMHNP to meet the challenges of health care reform and
      service delivery.

PMID- 22999031
TI  - Improving quality and safety in graduate education using an electronic student
      tracking system.
AB  - TOPIC: The Institute of Medicine report on the future of nursing, the Quality and
      Safety Education for Nurses initiative, and the Technology Informatics Guiding
      Education Reform movement are among the most prominent forces guiding change
      related to information technology and informatics in nursing to improve quality
      and safety in practice. Informatics competencies are essential for psychiatric
      nurses to leverage and integrate information technology into education, practice,
      and research. PURPOSE: This article examines informatics and information
      technology from the perspective of educational preparation of the psychiatric
      mental health nurse practitioner. SOURCES OF INFORMATION: Literature related to
      informatics, information technology, and quality and safety in advanced practice
      psychiatric nursing. CONCLUSION: Strategies for integration of information
      technology in educating psychiatric mental health nurse practitioner students are
      described. Informatics competency will result in safer and higher quality care.

PMID- 22999032
TI  - The effect of a pedagogy of curriculum infusion on nursing student well-being and
      intent to improve the quality of nursing care.
AB  - AIM: The aim of this study was to determine if a pedagogy of curriculum infusion
      promotes nursing student well-being and intent to address quality care indicators
      of Quality and Safety Education for Nurses (QSEN) and American Association of
      Colleges of Nursing. METHODS: This mixed-method experimental design study is
      based on 86 students' experiences with curriculum infusion as an intervention in
      two undergraduate nursing courses from August to December 2011. Student
      reflections, case analyses, and narrative evaluations were examined. FINDINGS:
      Students experiencing curriculum infusion demonstrated intention to provide
      quality care as evidenced by case analysis and personal reflections. CONCLUSION:
      Students acknowledged the importance of self-care and demonstrated intention to
      provide quality nursing care in five of the six QSEN competencies. Educators must
      be mindful to educate the whole student.

PMID- 22999033
TI  - Integrating the transitional relationship model into clinical practice.
AB  - BACKGROUND: The challenge of facilitating knowledge translation in clinical
      practice includes enabling practitioners and agencies to implement a common set
      of best practices, such as the Transitional Relationship Model (TRM). In 1992, a
      participatory action project implemented the TRM on a long-term psychiatric
      hospital ward in Ontario, Canada. All participants were successfully "bridged" to
      the community. Despite positive outcomes associated with the TRM, implementation
      of any best practice is difficult because it involves changing processes.
      OBJECTIVE: It was hypothesized that using multiple implementation strategies
      developed by wards that had already implemented the model would result in
      improved TRM implementation. METHOD: This study compared three groups of hospital
      wards; Group A wards had already adopted the TRM, Group B wards implemented the
      TRM in Year 1, and Group C wards implemented the TRM in Year 2. An iterative
      process was used in which strategies suggested by the A wards were used to
      enhance implementation on the B and C wards, respectively. These included
      enhancing staff participation, creating/maintaining supportive ward milieus,
      meeting specific educational needs, and supporting managers throughout the
      implementation process. The degree of actual implementation on each ward served
      as the primary outcome measure. RESULTS: Group C implemented the TRM model
      significantly quicker than the other groups. Sustainability in the initial A
      wards required the implementation of additional strategies used by the later
      wards.

PMID- 22999034
TI  - The described experience of primary caregivers of children with mental health
      needs.
AB  - About 10% of our nation's children have serious mental health needs that result
      in significant functional impairments. Although research has found that primary
      caregivers of children with mental health needs have high levels of depressive
      symptoms and distress, little is known about the challenges these caregivers
      face. Focus groups with 20 caregivers of children with mental health needs
      between 2 and 17 years of age revealed these themes: struggling with care
      systems, living in fear, being burdened and exhausted, worrying about the rest of
      the family, and having good things happen. Caregivers described extreme
      challenges and many unmet needs that are important to consider in efforts to
      improve both children's and caregivers' well-being.

PMID- 22999035
TI  - Perspectives of Japanese mothers with severe mental illness regarding the
      disclosure of their mental health status to their children.
AB  - This study examined Japanese mothers with severe mental illness and their
      perspectives about disclosing their mental health status to their children.
      Seventy-four outpatients diagnosed with schizophrenia or mood disorders were
      recruited. We utilized a cross-sectional design and a self-report questionnaire.
      Approximately 72% of the participants disclosed their mental health status to
      their children. The reasons for disclosure and nondisclosure varied. Our findings
      indicate that although both the disclosing and nondisclosing groups held beliefs
      about disclosure, many mothers appeared to struggle with these issues. It is
      essential that clinicians are aware of this issue so they may appropriately help
      the mothers.

PMID- 22999036
TI  - An exploratory study of the effectiveness of group narrative therapy on the
      school behavior of girls with attention-deficit/hyperactivity symptoms.
AB  - This study explored the effectiveness of group narrative therapy for improving
      the school behavior of a small sample of girls with attention
      deficit/hyperactivity disorder (ADHD). Fourteen clinics referred 9- to 11-year
      old girls with a clinical diagnosis of ADHD were randomly assigned to treatment
      and wait-list control groups. Posttreatment ratings by teachers showed that
      narrative therapy had a significant effect on reducing ADHD symptoms 1 week after
      completion of treatment and sustained after 30 days.

PMID- 22999037
TI  - The role of nonverbal cognitive ability in the association of adverse life events
      with dysfunctional attitudes and hopelessness in adolescence.
AB  - The aim of this study was to test whether nonverbal cognitive ability buffers the
      effect of life stress (number of adverse life events in the last year) on
      diatheses for depression. It was expected that, as problem-solving aptitude,
      nonverbal cognitive ability would moderate the effect of life stress on those
      diatheses (such as dysfunctional attitudes) that are depressogenic because they
      represent deficits in information-processing or problem-solving skills, but not
      on diatheses (such as hopelessness) that are depressogenic because they represent
      deficits in motivation or effort to apply problem-solving skills. The sample
      included 558 10- to 19-year-olds from a state secondary school in London.
      Nonverbal cognitive ability was negatively associated with both dysfunctional
      attitudes and hopelessness. As expected, nonverbal cognitive ability moderated
      the association between life adversity and dysfunctional attitudes. However,
      hopelessness was not related to life stress, and therefore, there was no life
      stress effect for nonverbal cognitive ability to moderate. This study adds to
      knowledge about the association between problem-solving ability and depressogenic
      diatheses. By identifying life stress as a risk factor for dysfunctional
      attitudes but not hopelessness, it highlights the importance of considering
      outcome specificity in models predicting adolescent outcomes from adverse life
      events. Importantly for practice, it suggests that an emphasis on recent life
      adversity will likely underestimate the true level of hopelessness among
      adolescents.

PMID- 22999038
TI  - Autobiographical accounts of sensing in Asperger syndrome and high-functioning
      autism.
AB  - Sensory experiences in Asperger syndrome (AS) or high-functioning autism (HFA)
      were explored by qualitative content analysis of autobiographical texts by
      persons with AS/HFA. Predetermined categories of hyper- and hyposensitivity were
      applied to texts. Hypersensitivity consists of strong reactions and heightened
      apprehension in reaction to external stimuli, sometimes together with overfocused
      or unselective attention. It was common in vision, hearing, and touch. In
      contrast, hyposensitivity was frequent in reaction to internal and body stimuli
      such as interoception, proprioception, and pain. It consists of less
      registration, discrimination, and recognition of stimuli as well as cravings for
      specific stimuli. Awareness of the strong impact of sensitivity is essential for
      creating good environments and encounters in the context of psychiatric and other
      health care.

PMID- 22999039
TI  - Reflections and lessons about international team building for research.

PMID- 22999040
TI  - Teaching recovery concepts to mental health technicians.

PMID- 22999041
TI  - Quick screen to detect current substance use disorder in adolescents and the
      likelihood of future disorder.
AB  - AIMS: A brief screen requiring 3-4min administration time was developed to detect
      adolescents qualifying for current substance use disorder (SUD) and those who
      will subsequently manifest SUD by early adulthood. METHODS: The revised Drug Use
      Screening Inventory (DUSI-R; Tarter, 1990) was administered to 329 boys on three
      occasions (ages 12-14, 15-17 and 18-19years of age). Principal components
      analysis yielded a core set of items to form three age-specific versions of the
      DUSI-R Quick Screen (DQS), consisting of the Substance Involvement Index and
      Problems Severity Index. RESULTS: Construct, concurrent and predictive validity
      of the DQS were in the good to excellent range. Sensitivity of the DQS at ages 12
      14, 15-17 and 18-19 for detecting current SUD was 100%, 93% and 93%. The DQS at
      these ages predicted SUD by age 22 with 73%, 77% and 83% accuracy. Replication in
      another sample revealed sensitivity of 71% and 75% in 15-17 and 18-20year old
      males. CONCLUSIONS: The true positive rate of detecting current and future SUD
      suggests that the DQS is an efficient screen for identifying youths requiring
      treatment or secondary prevention.

PMID- 22999042
TI  - Acute kidney injury in intensive care units according to RIFLE classification: a
      population-based study.
AB  - INTRODUCTION: Recent studies of the incidence of acute kidney injury (AKI) are
      largely based on estimated baseline serum creatinine values. The aim of this
      study was to more accurately determine the incidence of AKI using the RIFLE
      criteria for intensive care unit (ICU) patients of a whole population. MATERIALS
      AND METHODS: All adult patients admitted to the ICUs of Landspitali - The
      National University Hospital of Iceland in 2007 (n = 1026) were studied with
      meticulous search for baseline creatinine. The underlying risk factors and
      contributing causes for AKI were defined, and survival and ratio of end-stage
      renal failure evaluated. RESULTS: A measured baseline creatinine value was found
      for all but two patients with AKI. The incidence of AKI according to RIFLE
      criteria was 21.7% [95% confidence interval (CI): 19.0-24.1%], with 7.1% (95 CI:
      5.6-8.9%), 6.8% (95 CI: 5.3-8.5%) and 7.8% (95 CI: 6.2-9.6%) in the risk, injury
      and failure subgroups. Using estimated baseline creatinine overestimated the
      incidence of AKI by 3.5%. The sensitivity and specificity of the RIFLE criteria
      using estimated baseline creatinine were 76% and 95%. Renal replacement therapy
      was required for 17% of the AKI patients. One year survival of AKI patients was
      51%, but only 2.5% of patients surviving 90 days required chronic renal
      replacement therapy. CONCLUSIONS: The incidence of AKI in the ICU was lower than
      previously published, perhaps due to overestimation of AKI using estimated
      baseline creatinine or bias from tertiary referrals. AKI patients have high
      mortality, but the survivors have a low incidence of end-stage renal failure.

PMID- 22999043
TI  - Effective temperature for sheared suspensions: a route towards closures for
      migration in bidisperse suspension.
AB  - By extending the concept of an effective temperature, earlier introduced for
      sheared monodisperse suspensions, we propose a continuum theory for sheared
      bidisperse suspensions. We show the theory for sheared suspensions can be
      constructed from the theory for Brownian suspensions by replacing the temperature
      with the effective temperature. Furthermore, we explore the validity of closure
      relations based on mean field/free volume theory, by comparison with experimental
      data obtained for Brownian bidisperse suspensions. In a recent paper, we have
      shown that the new theory, combined with the discussed closure relations, is
      indeed a predictive theory.

PMID- 22999044
TI  - Electronic transfer as a route to increase the chemical stability in gold and
      silver core-shell nanoparticles.
AB  - This review article presents the collected recent findings and advancements in
      understanding and manipulating the electronic properties of the Au/Ag NP system
      from the standpoint of controlling the characteristics of heterostructured core
      shell NPs. The discovery of the electronic transfer effect through analysis of
      both Ag-Au and Au-Ag type NPs inspired the analysis of the resulting enhanced
      properties. First, the background on the synthesis and characterization of Ag,
      Au, Ag-Au, Au-Ag and Au-Ag-Au NPs, which will be used as a basis for studying the
      electronic transfer and stability properties is presented. Next, Mie Theory is
      used to inspect the optical properties of the Ag-Au NPs, revealing subtle
      structural characteristics in these probes, which has implications to the
      plasmonic properties. This is followed by the inspection of the electronic
      properties of the Au-Ag NPs primarily through XPS and XANES analysis, revealing
      the origins of the electronic transfer phenomenon. The unique electronic
      properties are then revealed to result in improved particle stability in terms of
      susceptibility to oxidation. Finally, an assessment of the resulting enhanced
      plasmonic sensing properties is discussed. The results are presented in terms of
      synthesis technique, material characterization, understanding of the electronic
      properties and manipulation of those properties to create Au-Ag NPs with enhanced
      resistance to oxidation and galvanic replacement.

PMID- 22999045
TI  - Learning from low-resource maternity care using pregnancy outcomes from the
      Solomon Islands.

PMID- 22999046
TI  - Somatostatin treatment of a persistent chyloperitoneum following abdominal aortic
      surgery.
AB  - Chyloperitoneum is an uncommon but serious complication of abdominal aortic
      surgery. There are no optimal guidelines for the management of chyloperitoneum.
      We present here our experiences regarding the treatment of chyloperitoneum with
      somatostatin for three patients who underwent surgery for abdominal aortic
      disease. Milky, odorless liquid was observed in the abdominal drain of these
      patients. The conservative treatment with total parenteral nutrition failed;
      therefore, in parallel, we initiated a somatostatin treatment as a continuous
      perfusion. Drain loss decreased in all up to the second day of treatment. The
      probable mechanisms of the somatostatin decrease the intestinal absorption of
      fats via the specific receptors, decrease triglyceride concentration in the
      thoracic duct, and attenuate lymph flow in the major lymphatic channels. The
      presented cases showed successful treatment using somatostatin and may be a new
      generation of effective treatments for chyloperitoneum.

PMID- 22999048
TI  - Analysis of the treatment of congenital vascular malformations using a
      multidisciplinary approach.
AB  - BACKGROUND: Vascular malformations are a rare and complex group of lesions which
      may present serious pitfalls in diagnosis and management. We sought to evaluate
      the efficacy and safety of our imaging protocol and therapeutic algorithm in the
      treatment of low-flow and high-flow vascular malformations in a large series of
      patients. METHODS: A prospective database of all patients treated by the
      multidisciplinary vascular malformation team at our institution between 2006 and
      2011 was reviewed. Management decisions were based on patients' clinical profile
      as well as critical lesion characteristics, and included conservative care,
      sclerotherapy, embolization, surgical resection, or a combination of these
      modalities. Treatment goals and expectations were established by the patient and
      physician at the time of initial evaluation. An outcomes grading system based on
      patient- and physician-derived treatment goals and assessment of response to
      management was applied (1 = worse; 2 = unchanged, 3 = significantly improved, 4 =
      completely resolved), and postprocedural complications were identified. RESULTS:
      The 136 vascular malformations in 135 patients included 59 (43.7%) males and 76
      (56.3%) females, ranging in age from under 1 year to 68 years (mean, 25.3 +/-
      17.0 years). In order to facilitate application of the therapeutic algorithm, all
      patients underwent dynamic contrast-enhanced magnetic resonance imaging to
      determine critical lesion characteristics, including flow quality and lesion
      extension. Of the 105 low-flow vascular malformations (LFVM), 23 (21.9%) were
      managed conservatively, 38 (36.2%) were treated with sclerotherapy (sodium
      tetradecyl sulfate, polidocanol, and/or ethanol), 18 (17.1%) were surgically
      resected, and eight (7.6%) were managed with a combination of modalities. Of the
      31 high-flow vascular malformations (HFVM), eight (25.8%) were managed
      conservatively, eight (25.8%) were treated with transcatheter arterial
      embolization, six (19.4%) required embolization followed by sclerotherapy, and
      five (16.1%) were primarily resected. Patients in all groups managed
      conservatively had minimal alteration in status. Response to sclerotherapy in the
      LFVM group resulted in improvement in 32 (84.2%) patients, surgical resection
      resulted in improvement in 16 (88.9%) patients, and combination therapy resulted
      in improvement in eight (100%) patients. Treatment with embolization in the HFVM
      group resulted in improvement in seven (87.5%) patients, while combination
      therapy resulted in improvement in six (100%), and surgical resection led to
      improvement in four (80%). Complications were observed in six (6.8%) patients
      treated for LFVMs (0 with sodium tetradecyl sulfate or polidocanol, four with
      ethanol, two with resection), and two (7.4%) patients treated for HFVMs with
      embolization or combination therapy. CONCLUSIONS: In this large cohort of
      vascular malformation patients, implementation of the proposed diagnostic and
      therapeutic algorithms in a multidisciplinary setting resulted in favorable
      outcomes with an acceptable complication rate in this challenging patient
      population.

PMID- 22999049
TI  - Electrospun Ni-added SnO2-carbon nanofiber composite anode for high-performance
      lithium-ion batteries.
AB  - The SnO(2) anode is a promising anode for next-generation Li ion batteries
      because of its high theoretical capacity. However, it exhibits inherent capacity
      fading because of the large volume change and pulverization that occur during the
      charge/discharge cycles. The buffer matrix, such as electrospun carbon nanofibers
      (CNFs), can alleviate this problem to some extent, but SnO(2) particles are
      thermodynamically incompatible with the carbon matrix such that large Sn
      agglomerates form after carbonization upon melting of the Sn. Herein, we
      introduce well-dispersed nanosized SnO(2) attached to CNFs for high-performance
      anodes developed by Ni presence. The addition of Ni increases the stability of
      the SnO(2) such that the morphologies of the dispersed SnO(2) phase are modified
      as a function of the Ni composition. The optimal adding composition is determined
      to be Ni:Sn = 10:90 wt % in terms of the crystallite size and the distribution
      uniformity. A high capacity retention of 447.6 mA h g(-1) after 100 cycles can be
      obtained for 10 wt % Ni-added SnO(2)-CNFs, whereas Ni-free Sn/SnO(2)-CNFs have a
      capacity retention of 304.6 mA h g(-1).

PMID- 22999050
TI  - A single-nucleotide polymorphism rs708567 in the IL-17RC gene is associated with
      a susceptibility to and the curve severity of adolescent idiopathic scoliosis in
      a Chinese Han population: a case-control study.
AB  - BACKGROUND: Although the pathogenesis of adolescent idiopathic scoliosis (AIS)
      remains controversial, genetic factors are thought to play key roles in the
      development of AIS. In a recent genome-wide association study, a polymorphism in
      the interleukin-17 receptor C (IL-17RC) gene was reported to be associated with
      the susceptibility to AIS, implicating IL-17RC as a novel predisposing gene for
      AIS. However, as this association has not been replicated in other populations,
      its global applicability remains unclear. METHODS: A total of 529 Chinese girls
      with AIS and 512 healthy age-matched controls were recruited in this case-control
      study from June 2007 to December 2009. Polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) analysis was performed to detect the
      genotype of the single-nucleotide polymorphism (SNP) rs708567 in the IL-17RC
      gene. Case-control and case-only studies were performed to determine the
      association between the IL-17RC gene polymorphism and the susceptibility to and
      curve severity of AIS. RESULTS: The GG genotype and G allele frequencies were
      significantly higher in the AIS patients than in the controls (chi2 test: P =
      0.023 and 0.028, respectively). The risk for the GG genotype is 1.550-fold (95%
      CI: 1.062 - 2.261) higher than the AG genotype, and the risk for the G allele is
      1.507-fold (95% CI: 1.046 - 2.172) higher than the A allele. Additionally, a
      subgroup of skeletally mature AIS patients (n = 241) who carried the GG genotype
      showed a significantly higher mean maximum Cobb angle than those carrying the AG
      genotype (36.01 +/- 13.12 degrees  vs. 28.92 +/- 7.43 degrees , P = 0.007).
      CONCLUSIONS: This study confirms the significant association between the IL-17RC
      gene polymorphism and the susceptibility to and curve severity of AIS in a
      Chinese Han population, suggesting that the IL-17RC gene is an AIS-predisposing
      gene in Chinese Han population.

PMID- 22999053
TI  - Arnoldiellina fluorescens gen. et sp. nov.--a new green autofluorescent
      foraminifer from the Gulf of Eilat (Israel).
AB  - A new monothalamous (single-chambered) soft-walled foraminiferal species,
      Arnoldiellina fluorescens gen. et sp. nov., was isolated from samples collected
      in the Gulf of Eilat, Israel. The species is characterized by a small elongate
      organic theca with a single aperture of allogromiids. It is characterized by the
      emission of green autofluorescence (GAF) that has so far not been reported from
      foraminifera. Phylogenetic analysis of a fragment of the 18S rDNA indicates that
      the species is related to a group of monothalamous foraminiferans classified as
      clade I. Although the morphology of the new species is very different compared to
      the other members of this clade, a specific helix in 18S rRNA secondary structure
      strongly supports this position.

PMID- 22999052
TI  - Exploring the reach and program use of Hello World, an email-based health
      promotion program for pregnant women in the Netherlands.
AB  - BACKGROUND: In 2006, the Dutch government initiated Hello World, an email-based
      program promoting healthy lifestyles among pregnant women through quizzes with
      pregnancy-related questions. In 2008, an updated version was released.The present
      study aimed to (1) examine the reach of Hello World and the representativeness of
      its users for all pregnant women in the Netherlands, (2) explore the relationship
      between program engagement and lifestyle characteristics, and (3) explore the
      relationship between the program content participants accessed (content on
      smoking, physical activity, and nutrition) and their lifestyle characteristics.
      METHODS: Data from 4,363 pregnant women were included. After registration, women
      received an online questionnaire with demographic and lifestyle questions. To
      evaluate their representativeness, their demographic characteristics were
      compared with existing data for Dutch (pregnant) women. Women were classified on
      the following lifestyle characteristics: smoking, nutrition, physical activity,
      and pre-pregnancy weight status. Program use was tracked and the relationships
      between lifestyle characteristics, program engagement, and the percentage of
      smoking, physical activity, and nutrition questions accessed after opening a quiz
      were explored using Mann-Whitney U tests and Kruskal-Wallis tests. RESULTS: Hello
      World reached +/-4% of its target population. Ten percent of participants were
      low educated and 22% immigrants. On average, women received 6.1 (SD:2.8) quiz
      emails and opened 32% of the associated quizzes (2.0, SD:2.1). A significant
      positive association was found between the number of quizzes opened and the
      number of healthy lifestyle characteristics. After opening a quiz, women accessed
      most smoking, nutrition, and physical activity questions. Significant
      relationships were found between several lifestyle characteristics and the
      percentage of smoking, physical activity, and nutrition questions accessed.
      However, between-group differences were small, quiz topics were largely unrelated
      to their lifestyle characteristics, and inconsistencies were found regarding the
      directions of these associations. CONCLUSIONS: Hello World reached +/-4% of its
      target population, which is lower than the reach of its previous version (+/-8%).
      Relatively few low educated and immigrant women registered for the program.
      Active participation in the program was positively associated with the number of
      healthy behaviours participants engaged in. The program content participants
      chose to access was largely unrelated to their lifestyle characteristics.

PMID- 22999054
TI  - A modified dilution method reveals higher protozoan growth rates than the size
      fractionation method.
AB  - Protozoan growth rates are typically estimated with the size fractionation method
      in which the organisms studied are separated from the larger grazers. This method
      was compared with a specially modified dilution method which removed not only the
      grazing pressure of larger grazers but also that of predators of the same size as
      the organisms studied. Five comparisons were performed under natural conditions
      with the following marine protozoa: Balanion comatum (3 sets of data), Ebria
      tripartita, and Strombidium sp. The dilution method revealed significantly higher
      growth rates (Wilcoxon's signed-rank test, p=0.04), which underscores the
      importance of predation between organisms of the same size. It directly
      demonstrated that the size fractionation method may significantly underestimate
      protozoan growth rates.

PMID- 22999055
TI  - Does intravascular ultrasound provide clinical benefits for percutaneous coronary
      intervention with bare-metal stent implantation? A meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: The role of intravascular ultrasound (IVUS) in percutaneous coronary
      interventions (PCI) is still controversial despite several previously published
      meta-analyses. A meta-analysis to evaluate the controversial role of IVUS-guided
      PCI with bare-metal stenting was performed and a previous published meta-analysis
      was re-evaluated in order to clarify the discrepancy between results of these
      studies. METHODS: A systematic review was performed by an electronic search of
      the PubMed, Embase and Web of Knowledge databases and by a manual search of
      reference lists for randomized controlled trials published until April 2011, with
      clinical outcomes and, at least, six months of clinical follow-up. A meta
      analysis based on the intention to treat was performed with the selected studies.
      RESULTS: Five studies and 1,754 patients were included. There were no differences
      in death (OR = 1.86; 95% CI = 0.88-3.95; p = 0.10), non-fatal myocardial
      infarction (OR = 0.65; 95% CI = 0.27-1.58; p = 0.35) and major adverse cardiac
      events (OR = 0.74; 95% CI = 0.49-1.13; p = 0.16). An analysis of the previous
      published meta-analysis strongly suggested the presence of publication bias.
      CONCLUSIONS: There is no evidence to recommend routine IVUS-guided PCI with bare
      metal stent implantation.  This may be explained by the paucity and heterogeneity
      of the studies published so far.

PMID- 22999056
TI  - The impact of forced displacement in World War II on mental health disorders and
      health-related quality of life in late life - a German population-based study.
AB  - BACKGROUND: Long-term effects of World War II experiences affect psychological
      and physical health in aged adults. Forced displacement as a traumatic event is
      associated with increased psychological burden even after several decades. This
      study investigates the contribution of forced displacement as a predictor for
      mental health disorders and adds the aspect of health-related quality of life
      (QoL). METHOD: A sample of 1,659 German older adults aged 60-85 years was drawn
      from a representative survey. Post-traumatic stress disorder (PTSD), somatoform
      symptoms, depressive syndromes, and health-related QoL were assessed as outcome
      variables. Chi-square and t-test statistics examined differences between
      displaced and non-displaced people. Logistic regression analyses were performed
      to examine the impact of forced displacement on mental health disorders and QoL.
      RESULTS: Displaced people reported higher levels of PTSD, depressive and
      somatoform symptoms, and lower levels of health-related QoL. Displacement
      significantly predicted PTSD and somatoform symptoms in late life, but not
      depressive disorders. Health-related QoL was predicted by forced displacement and
      socio-demographic variables. CONCLUSION: Forced displacement is associated with
      an elevated risk for PTSD and somatoform symptoms and lowered health-related QoL
      in aged adults. Its unique impact declines after including socio-demographic
      variables. Long-term consequences of forced displacement need further
      investigations and should include positive aspects in terms of resilience and
      protective coping strategies.

PMID- 22999057
TI  - Quality of colonoscopy: how to improve it?

PMID- 22999058
TI  - Resected biliary tract cancers: a novel clinical-pathological score correlates
      with global outcome.
AB  - BACKGROUND: Biliary tract cancer presents a poor prognosis. AIMS: The objective
      of this study is to find clinical-laboratory parameters like prognostic factors
      to select patients who can benefit from surgery and post-operative treatments.
      METHODS: Between 2005 and 2010, 41 patients underwent radical surgery at our
      Institution. A novel score was retrospectively calculated assigning a grade to
      the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively
      assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0
      and SCORE 1. RESULTS: Patients with cholangiocarcinoma or Klatskin tumours or
      asymptomatic at diagnosis presented a significantly better overall survival (OS)
      than patients with different primary sites or who presented pain, jaundice or
      cholangitis. At univariate analysis, high levels of aspartate aminotransferase,
      alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and
      after surgery had a negative correlation with OS. A worse OS was observed in
      patients with a higher score (median OS in the "score 0" group=30.79 months vs.
      median OS in the "score 1"=17.98 months). CONCLUSION: Our results suggest that
      pre and post-surgery clinical-laboratory parameters and the novel score, could be
      useful, especially for intrahepatic tumours, in predicting the outcome in
      patients undergoing surgery and in selecting patients to receive adjuvant
      therapy.

PMID- 22999059
TI  - Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for
      colorectal carcinoma in Europeans.
AB  - BACKGROUND: Colon carcinogenesis is associated with increased expression levels
      of Toll-like receptor 2 and Toll-like receptor 4. AIM: To determine in a
      Caucasian population the role of Toll-like receptor 2 and Toll-like receptor 4
      polymorphisms in colorectal cancer development. METHODS: Hospital based
      multicentre case control study involving 193 colorectal cancer patients and 278
      healthy individuals. DNA samples were extracted from blood cells and genotyping
      of TLR2+597T>C, TLR2-4760T>C, TLR4-3745A>G, TLR2Arg753Gln, TLR4Asp299Gly was
      performed. Functionality of risk polymorphisms was evaluated through production
      of TNF-alpha in cell culture and Toll-like receptors levels quantified by real
      time RT-PCR. RESULTS: TLR2+597CC homozygous had 5-fold decreased risk (odds ratio
      (OR)=0.21, 95% CI: 0.09-0.50, p<0.001) and TLR4 299Gly homozygous 3-fold
      increased risk of colorectal cancer (OR=3.30, 95% CI: 1.18-9.28, p=0.015). In
      stratified analysis, TLR2+597CC genotype protective effect was even higher in
      overweight individuals (OR=0.17, 95% CI: 0.06-0.53, p<0.001) and in never smokers
      (OR=0.11, 95% CI: 0.02-0.51, p=0.001). Also, the increased risk effect for TLR4
      299Gly homozygous genotype was higher in overweight individuals (OR=8.67, 95% CI:
      1.11-87.85, p=0.011). TLR2+597T>C polymorphism conferred 41% less (p=0.03) and
      TLR4Asp299Gly 65% more TNF-alpha production (p=0.02) with no differences in Toll
      like receptors levels. CONCLUSION: Functional Toll-like receptor 2 and Toll-like
      receptor 4 polymorphisms significantly alter the risk to have colorectal cancer.
      Obesity and smoking may influence the risk for colorectal cancer in individuals
      presenting these genetic profiles.

PMID- 22999060
TI  - Induction of interleukin 2 expression in the liver for the treatment of H22
      hepatoma in mice.
AB  - BACKGROUND AND AIMS: We designed this study to evaluate the ability of a plasmid
      carrying an RU486 regulatory system to induce expression of interleukin-2 (IL-2)
      gene and to examine the antitumour efficacy of the induced IL-2 gene. METHODS:
      The plasmid pRS-mIL-2,which contains an RU486 inducible system and IL-2 gene was
      injected into mice. Sera and tissues from liver, spleen, lungs and kidneys were
      taken to test the properties of the plasmid. To examine the antitumour efficacy
      of pRS-mIL-2, tumours were established in the liver by direct inoculation of H22
      hepatoma cells. RESULTS: The IL-2 levels in serum correlated with the dose of
      plasmid and RU486. High and sustained IL-2 levels could be achieved by
      administration of RU486 every day. The mRNA of transgene IL-2 was found only in
      the liver. Treatment of mice with pRS-mIL-2 plus RU486 resulted in the
      significant reduction in tumour volume compared with control groups. CONCLUSIONS:
      Tight temporal and spatial control of transgene IL-2 expression can be achieved
      by a plasmid containing an RU486 inducible system driven by liver specific
      promoter. pRS-mIL-2 exhibited strong antitumour efficacy following consecutive
      induction with RU486.

PMID- 22999062
TI  - Cerebral microvascular effects of nimodipine in combination with soman.
AB  - Nimodipine, a calcium antagonist, has been shown to increase the detoxification
      of soman. In this study the cerebral microcirculatory effects of nimodipine and
      the acetylcholinesterase inhibitor soman was studied. Anaesthetised rats were
      administered nimodipine, 10 mg kg(-1) or vehicle intra-peritoneally, and 1h later
      exposed to 45 MUg kg(-1) soman intravenously. The regional blood flows were
      measured using the microsphere method. Nimodipine and soman markedly increased
      the cerebral blood flow (CBF) and reduced the vascular resistance. Total CBF
      increased by 146% after nimodipine and by 105% after soman administration.
      Combined administration of nimodipine and soman caused additional but not fully
      additive effects on CBF and vascular resistance, indicating possible different
      mechanisms of the two agents. A part of the nimodipine induced increased
      detoxification after AChE-inhibition may be associated with this cerebral
      vasodilation.

PMID- 22999061
TI  - Preoperative Cyfra21-1 and SCC-Ag serum titers predict survival in patients with
      stage II esophageal squamous cell carcinoma.
AB  - BACKGROUND: The purpose of this study is to evaluate the predictive significance
      of preoperative serum level of cytokeratin 19 fragments (Cyfra21-1) and squamous
      cell carcinoma antigen (SCC-Ag) after complete resection in patients with stage
      II esophageal squamous cell carcinoma (ESCC). METHODS: Between 1995 and 2006, a
      total of 379 patients in stage II ESCC who underwent complete resection were
      consecutively recruited. Statistical analyses were applied to test the
      associations between preoperative serum titers of Cyfra21-1 and SCC-Ag,
      clinicopathological factors and prognoses. RESULTS: Preoperative high and normal
      serum level of Cyfra21-1 and SCC-Ag were found in 47.8%, 52.2% and 72.8%, 27.2%,
      respectively. The 1-, 3-, 5-year overall survival rate for the entire cohort of
      patients was 95%, 78%, and 56%, respectively. Median overall survival (OS) was
      45.3 months longer in patients with low preoperative serum level of Cyfra21-1
      (91.9 months) than those with high preoperative serum level of Cyfra21-1 (46.6
      months) (P < 0.001). Median OS among patients with SCC-Ag-low level was also
      longer than those with SCC-Ag-high level (89.7 vs. 63.7 months, P < 0.001),
      especially for those with stage IIB (P < 0.001). After multivariate analysis,
      along with pTNM stage, preoperative serum level of Cyfra21-1 and SCC-Ag were
      independently and significantly predictive factors (P < 0.001, P < 0.001).
      Furthermore, the five-year survival rate in double-low subset, either-low subset
      and double-high subset was 100%, 83% and 27%, respectively (P < 0.001).
      CONCLUSIONS: The preoperative serum level of Cyfra21-1 and SCC-Ag are
      independently significant predictors which negatively affected the survivals of
      patients with stage II ESCC.

PMID- 22999063
TI  - Photo-oxidative stress by ultraviolet-B radiation and antioxidative defense of
      eckstolonol in human keratinocytes.
AB  - Ultraviolet-B (UV-B) irradiation has been known to generate oxidative stress by
      increasing reactive oxygen species (ROS) in skin cells. Several naturally
      occurring antioxidant compounds isolated from marine algae are believed to
      protect against ROS. In this study, we assessed the antioxidative effect of
      eckstolonol isolated from Ecklonia cava against UV-B-induced ROS in human
      keratinocytes (HaCaTs). We investigated the effects of photo-oxidative stress by
      UV-B (50 mJ/cm(2)) and the antioxidative effects of eckstolonol using
      fluorometry, flow cytometry, microscopy, and cell viability and comet assays. UV
      B irradiation decreased cell viability, which was restored in a dose-dependent
      manner with eckstolonol treatment (0, 5, 50, 100, and 200 MUM). Moreover,
      eckstolonol reduced UV-B-induced ROS, lipid peroxidation, damaged DNA levels, and
      cell death. These antioxidative effects seem to be due to the enzymatic
      activities of catalase (CAT) and superoxide dismutase (SOD). Collectively, these
      results indicate that eckstolonol is capable of protecting keratinocytes from
      photo-oxidative stress.

PMID- 22999064
TI  - Crohn's disease affecting the small bowel is associated with reduced appetite and
      elevated levels of circulating gut peptides.
AB  - BACKGROUND & AIMS: Appetite disturbance is an important nutritional issue in
      Crohn's disease (CD), but the biological basis is unclear. Satiety signals such
      as polypeptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are produced by
      enteroendocrine cells (EEC). In animal models, upregulation of EEC plays a
      mechanistic role in feeding disturbance and weight loss. We recently showed
      increased EEC activity in tissue from active small bowel CD. This study
      investigated EEC products in plasma in CD, and appetite-related symptoms.
      METHODOLOGY: Active CD patients and a healthy reference group were studied. Gut
      peptide responses to a mixed nutrient test meal were measured by ELISA. Symptoms
      were assessed by visual analogue score. A patient subset was re-studied in
      remission. RESULTS: CD subjects displayed reduced appetite (p < 0.0001) before
      and after eating. Total PYY was increased 2.2-fold (p = 0.04) and correlated with
      nausea (p = 0.036) and bloating (p = 0.037) scores only in small bowel CD.
      Postprandial plasma ghrelin levels were also elevated. Leptin correlated with
      body mass index (p = 0.0001) and weight loss (p = 0.01). GLP-1 and GIP were not
      elevated. In remission, postprandial PYY and ghrelin reverted to control levels.
      DISCUSSION: Enhanced EEC responses may directly and adversely affect appetite in
      CD patients through increased gut-brain signalling.

PMID- 22999065
TI  - The Mediterranean diet improves the systemic lipid and DNA oxidative damage in
      metabolic syndrome individuals. A randomized, controlled, trial.
AB  - BACKGROUND & AIMS: Metabolic syndrome (MetS), in which a non-classic feature is
      an increase in systemic oxidative biomarkers, presents a high risk of diabetes
      and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet)
      is associated with a reduced risk of MetS. However, the effect of the MedDiet on
      biomarkers for oxidative damage has not been assessed in MetS individuals. We
      have investigated the effect of the MedDiet on systemic oxidative biomarkers in
      MetS individuals. METHODS: Randomized, controlled, parallel clinical trial in
      which 110 female with MetS, aged 55-80, were recruited into a large trial
      (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary
      prevention of CVD. Participants were assigned to a low-fat diet or two
      traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet
      group participants received nutritional education and either free extra virgin
      olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad
      libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage
      base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year
      trial. RESULTS: After 1-year urinary F2-IP decreased in all groups, the decrease
      in MedDiet groups reaching a borderline significance versus that of the Control
      group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in
      both MedDiet groups versus the Control one (P < 0.001). CONCLUSIONS: MedDiet
      reduces oxidative damage to lipids and DNA in MetS individuals. Data from this
      study provide evidence to recommend the traditional MedDiet as a useful tool in
      the MetS management.

PMID- 22999066
TI  - Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid
      profile: a randomized clinical trial.
AB  - BACKGROUND & AIMS: Epidemiological data suggest that moderate red wine
      consumption reduces cardiovascular mortality and the incidence of diabetes.
      However, whether these effects are due to ethanol or to non-alcoholic components
      of red wine still remains unknown. The aim of the present study was to compare
      the effects of moderate consumption of red wine, dealcoholized red wine, and gin
      on glucose metabolism and the lipid profile. METHODS: Sixty-seven men at high
      cardiovascular risk were randomized in a crossover trial. After a run-in period,
      all received each of red wine (30 g alcohol/d), the equivalent amount of
      dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a
      randomized order. Fasting plasma glucose and insulin, homeostasis model
      assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins
      and adipokines were determined at baseline and after each intervention. RESULTS:
      Fasting glucose remained constant throughout the study, while mean adjusted
      plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine.
      HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin.
      Lipoprotein(a) decreased after the red wine intervention. CONCLUSIONS: These
      results support a beneficial effect of the non-alcoholic fraction of red wine
      (mainly polyphenols) on insulin resistance, conferring greater protective effects
      on cardiovascular disease to red wine than other alcoholic beverages.
      www.isrctn.org: ISRCTN88720134.

PMID- 22999067
TI  - A smaller endotracheal tube combined with intravenous lidocaine decreases post
      operative sore throat - a randomized controlled trial.
AB  - BACKGROUND: Post-operative sore throat (POST) has increasingly been a common
      clinical complication particularly in thyroid surgery. We conducted a trial to
      evaluate the effect of non-pharmacological [smaller-sized endotracheal tube
      (ETT)] combined with pharmacological intervention [lidocaine intravenous (i.v.)]
      on POST in women undergoing thyroid surgery. METHODS: Two hundred and forty
      patients scheduled for thyroid surgery were randomly divided into four groups:
      Group A, ETT size 7.0 with saline; Group B, ETT size 6.0 with saline; Group C,
      ETT size 7.0 with lidocaine; Group D, ETT size 6.0 with lidocaine. Patients in
      Groups C and D received i.v. 1.5 mg/kg lidocaine that was filled in syringe up to
      10 ml 5 min before induction of anaesthesia; whereas patients in Groups A and B
      received an equal volume of saline. The incidence and severity of POST were
      evaluated at 1, 6 and 24 h after tracheal extubation. RESULTS: The highest
      incidence of POST occurred at 6 h after extubation in all groups. The incidence
      of POST was significantly lower in Group D compared with Groups A (23% vs. 62%, P
      < 0.01), B (23% vs. 42%, P = 0.03) and C (23% vs. 43%, P = 0.02) at 6 h after
      extubation. Group D had significantly decreased severity of POST compared with
      Groups A, B and C 6 and 24 h after extubation (P < 0.05). CONCLUSION: Use of
      smaller-sized ETT combined with i.v. lidocaine decreases the incidence and
      severity of POST in women undergoing thyroid surgery.

PMID- 22999068
TI  - L-type Ca2+ channel function during Timothy syndrome.
AB  - Voltage-gated, dihydropyridine-sensitive L-type Ca(2+) channels are multimeric
      proteins composed of a pore-forming transmembrane alpha(1) subunit (Ca(v)1.2) and
      accessory beta, alpha(2)delta, and gamma subunits. Ca(2+) entry via Ca(v)1.2
      channels shapes the action potential (AP) of cardiac myocytes and is required for
      excitation-contraction coupling. Two de novo point mutations of Ca(v)1.2 glycine
      residues, G406R and G402S, cause a rare multisystem disorder called Timothy
      syndrome (TS). Here, we discuss recent work on the mechanisms by which Ca(v)1.2
      channels bearing TS mutations display slowed inactivation that leads to increased
      Ca(2+) influx, prolonging the cardiac AP and promoting lethal arrhythmias. Based
      on these studies, we propose a model in which the scaffolding protein AKAP79/150
      stabilizes the open conformation of Ca(v)1.2-TS channels and facilitates physical
      interactions among adjacent channels via their C-tails, increasing the activity
      of adjoining channels and amplifying Ca(2+) influx.

PMID- 22999069
TI  - Primary mesenchymal chondrosarcoma of the kidney with synchronous implant and
      infiltrating urothelial carcinoma of the ureter.
AB  - Primary mesenchymal chondrosarcoma of the kidney is rare, and it shows distinct
      undifferentiated tumor cells and well differentiated cartilagenous components.
      Also assident infiltrating urothelial carcinoma of the ureter is an extremely
      rare cancer. We report a case of primary mesenchymal chondrosarcoma occurring in
      the left kidney with an ipsilateral and distinct distal ureteric implant, and a
      coexisting infiltrating urothelial carcinoma of the ureter in a 64-year-old man.
      Histopathological examination and immunohistochemical studuies showed the classic
      features of mesenchymal chondrosarcoma in kidney, as well as a few infiltrating
      urothelial in ureter. Multitarget fluorescence in situ hybridization (FISH)
      suggested that the development of the urothelial carcinoma in the ureter may be
      triggered or induced by the chondrosarcoma component. The patient died 2 month
      after left nephro-ureterectomy. This is the first reported case of a primary
      mesenchymal chondrosarcoma of the kidney with coexisting infiltrating urothelial
      carcinoma of the ureter. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1522835667751019.

PMID- 22999070
TI  - New pathways of increased cardiovascular risk in depression: a pilot study on the
      association of high-sensitivity C-reactive protein with pro-atherosclerotic
      markers in patients with depression.
AB  - BACKGROUND: An elevation of inflammatory markers such as high-sensitivity C
      reactive protein (hs-CRP) can be found in patients with depressive disorders.
      Inflammatory processes are known to influence atherosclerosis and might also
      mediate the link between depression and diabetes. The present study aimed at
      comparing hs-CRP and its relationship with atherogenic platelet markers in
      patients with type 2 diabetes (TD2) and/or newly diagnosed major depression (MD).
      METHODS: Hs-CRP concentrations in 24 patients with TD2, 21 patients with MD
      (diagnosed according to ICD-10 and DSM-IV), 19 patients with TD2 and comorbid MD,
      and 25 healthy controls were compared using analysis of variance. The
      relationship of hs-CRP with atherogenic platelet markers (CD40, CD40 ligand,
      soluble CD40L) were examined for the different samples using Pearson's
      correlations and regression analyses. RESULTS: Hs-CRP levels were not associated
      with depression (F(1, 80)=0.56, p=.814). There was a trend for higher hs-CRP in
      diabetes patients (p=.095), but not after adjustment for BMI. CD40 or sCD40L were
      not related to hs-CRP. For CD40L, regression analysis revealed a significant
      interaction between hs-CRP and subgroup: Hs-CRP was positively associated with
      CD40L only in depressed patients without diabetes (B=.334, p<.05). LIMITATIONS:
      Causal inferences are limited because of the cross-sectional design and the small
      sample size. CONCLUSIONS: Our results demonstrate preliminary evidence that hs
      CRP might contribute to the risk of cardiovascular disease in depressed patients
      without somatic diseases via its association with platelet expression of CD40L.
      Further studies are necessary to confirm these findings.

PMID- 22999071
TI  - Gender does not affect postdischarge outcomes in patients hospitalized for
      worsening heart failure with reduced ejection fraction (from the Efficacy of
      Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan [EVEREST]
      Trial).
AB  - Women have traditionally been underrepresented in heart failure (HF) trials, and
      their baseline characteristics and outcomes after hospitalization for HF are
      unclear. We retrospectively analyzed the clinical characteristics and outcomes of
      patients according to gender in the Efficacy of Vasopressin Antagonism in Heart
      Failure Outcome Study with Tolvaptan (EVEREST) trial. EVEREST randomized 4,133
      patients hospitalized for HF and ejection fraction of <=40% to tolvaptan or
      placebo, in addition to standard therapy. The median follow-up was 9.9 months.
      Log-rank tests and multivariate Cox regression models were used to compare the
      hazards of all-cause mortality and cardiovascular mortality or HF
      hospitalization. Women constituted 1,058 (26%) of the study population. The
      baseline characteristics were similar except that the women were older with more
      hypertension and diabetes and less chronic renal insufficiency, previous
      myocardial infarction, previous coronary revascularization, and baseline
      defibrillator implantation (all p <0.001). The baseline use of evidence-based HF
      medical therapies was similar between genders (all p >0.30). Despite a high event
      rate, no difference was seen in all-cause mortality (men 27% vs women 24%,
      multivariate hazard ratio 1.04, p = 0.61) or cardiovascular mortality plus HF
      hospitalization (men 42% vs women 39%, multivariate hazard ratio 1.11, p = 0.10)
      on univariate analysis or after adjusting for baseline covariates. In conclusion,
      women hospitalized for worsening HF with an ejection fraction of <=40% were
      older, had more hypertension, and had received fewer procedure-based
      interventions than men but had relatively similar HF medication usage and
      clinical findings. After hospitalization for HF, women have a similarly high risk
      of long-term HF morbidity and mortality compared with men.

PMID- 22999072
TI  - Comparison of the incidence of acute decompensated heart failure before and after
      the major tsunami in Northeast Japan.
AB  - On March 11, 2011, a huge tsunami attacked the northeastern coast of Japan after
      a magnitude 9 earthquake. No reports have investigated the impact of tsunamis on
      the incidence of cardiovascular disease, especially heart failure (HF). We
      investigated the number and clinical characteristics of hospitalized patients
      with acute decompensated HF (ADHF) in the east coast of Iwate hit by the tsunami
      (tsunami area) for a 12-week period around the disaster. For comparison with
      previous years, numbers of ADHF were surveyed in the corresponding area in 2009
      and 2010. In addition, to elucidate the impact of the tsunami, a similar study
      was performed in a remote area where the tsunami had minimal effect (control
      area). After the disaster, the number of patients with ADHF in the tsunami area
      was significantly increased compared to the predisaster period (relative risk
      1.97, 95% confidence interval 1.50 to 2.59). The peak was found 3 to 4 weeks
      after the disaster. In contrast, in the control area, no significant change in
      ADHF events was observed (relative risk 1.29, 95% confidence interval 0.94 to
      1.78). There was a significant correlation between changes in the number of ADHF
      admissions and percent tsunami flood area (r = 0.73, p <0.001) or the number of
      shelter evacuees (r = 0.83, p <0.001). In conclusion, these findings suggest that
      large and sudden changes in daily life and the trauma associated with a
      devastating tsunami have a significant impact on the incidence of ADHF.

PMID- 22999073
TI  - Effect of tailored antiplatelet therapy on periprocedural myonecrosis in patients
      with diabetes mellitus (from the DM-Verify Now Trial).
AB  - We investigated whether additional platelet inhibition with a glycoprotein
      IIb/IIIa inhibitor would be beneficial in reducing the risk of periprocedural
      myocardial infarction (PMI) in diabetic patients with high residual platelet
      reactivity (HPR). Patients with diabetes mellitus were administered aspirin and
      clopidogrel at a 300-mg loading dose 1 day before the procedure, and the
      VerifyNow P2Y(12) assay was performed just before percutaneous coronary
      intervention. Patients with HPR, defined as a P2Y(12) reaction unit of >=270 were
      randomly assigned to group A or control group C1. Patients without HPR were
      assigned to control group C2. Conventional anticoagulation with heparin was given
      to groups C1 and C2, and group A received additional abciximab treatment.
      Clinically relevant PMI was defined as any elevation in the biomarkers creatine
      kinase-MB isoenzyme and cardiac troponin I >3 times the upper normal limit
      measured 8, 16, or 24 hours after percutaneous coronary intervention. Of the
      patients, 47 and 51 were assigned to group A and C1; the clinical and procedural
      characteristics in the 2 groups were balanced. Of the 47 patients in group A and
      51 patients in group C1, 9 (19%) and 9 (18%), respectively, experienced a PMI
      event according to the creatine kinase-MB cutoff (p = 1.00), and 27 in group A
      (57%) and 29 in group C1 (57%) experienced a PMI event according to the troponin
      I cutoff (p = 1.00). Five minor bleeding events, including small and localized
      hematomas, were observed immediately after the procedure (4 in group A and 1 in
      group C1). Only 1 major bleeding event, retroperitoneal hemorrhage, was observed
      in group A. The patients in group C2 had a PMI event rate (50% of 32 patients, p
      = 1.00) similar to that of group C1. In conclusion, additional platelet
      inhibition using a tailored approach and a point-of-care assay did not improve
      the periprocedural outcome in diabetic patients with HPR.

PMID- 22999074
TI  - Lanostane triterpenoids and sterols from Antrodia camphorata.
AB  - Four lanostane triterpenes, 3,7,11-trioxo-5alpha-lanosta-8,24(E)-dien-26-oic
      acid, methyl 11alpha-3,7-dioxo-5alpha-lanosta-8,24(E)-dien-26-oate, methyl
      3,7,11,12,15,23-hexaoxo-5alpha-lanost-8-en-26-oate, and ethyl 3,7,11,12,15,23
      hexaoxo-5alpha-lanost-8-en-26-oate, two sterols, (14alpha,22E)-14-hydroxyergosta
      7,22-diene-3,6-dione and a steroid named as camphosterol A were isolated from a
      mixture of fruiting bodies and mycelia of solid cultures of Antrodia camphorata.
      The 1H and 13C NMR spectra of all compounds were fully assigned using a
      combination of 2D NMR experiments, including COSY, HMQC, HMBC and NOESY
      sequences. Six compounds were evaluated for cytotoxicity against several human
      tumor cell lines, all of which has moderate activity.

PMID- 22999075
TI  - Intra-session and inter-day reliability of forearm surface EMG during varying
      hand grip forces.
AB  - Surface electromyography (EMG) is widely used to evaluate forearm muscle function
      and predict hand grip forces; however, there is a lack of literature on its intra
      session and inter-day reliability. The aim of this study was to determine
      reliability of surface EMG of finger and wrist flexor muscles across varying grip
      forces. Surface EMG was measured from six forearm flexor muscles of 23 healthy
      adults. Eleven of these subjects undertook inter-day test-retest. Six repetitions
      of five randomized isometric grip forces between 0% and 80% of maximum force
      (MVC) were recorded and normalized to MVC. Intra- and inter-day reliability were
      calculated through the intraclass correlation coefficient (ICC) and standard
      error of measurement (SEM). Normalized EMG produced excellent intra-session ICC
      of 0.90 when repeated measurements were averaged. Intra-session SEM was low at
      low grip forces, however, corresponding normalized SEM was high (23-45%) due to
      the small magnitude of EMG signals. This may limit the ability to evaluate finer
      forearm muscle function and hand grip forces in daily tasks. Combining EMG of
      functionally related muscles improved intra-session SEM, improving within-subject
      reliability without taking multiple measurements. Removing and replacing
      electrodes inter-day produced poor ICC (ICC < 0.50) but did not substantially
      affect SEM.

PMID- 22999076
TI  - Hip internal rotation is correlated to radiographic findings of cam
      femoroacetabular impingement in collegiate football players.
AB  - PURPOSE: The objective of this study was to determine whether physical
      examinations (flexion-abduction-external rotation [FABER], impingement, range-of
      motion profiles) could be used to detect the bony abnormalities of
      femoroacetabular impingement (FAI) in an athletic population. METHODS: We
      performed a prospective study of 65 male collegiate football players. Both hips
      were evaluated by 2 orthopaedic surgeons for radiographic signs of FAI. The alpha
      angle and head-neck offset were measured on frog-leg lateral films. The center
      edge angle, acetabular index, crossover sign, and alpha angle were measured on
      anteroposterior films. Measurements were averaged for both observers. Maximum hip
      range of motion in flexion (supine) and internal/external rotation (supine,
      sitting, and prone) was measured with a goniometer. Pain provoked by the
      impingement and FABER tests was also recorded. Examinations were completed at 2
      of 4 stations (2 duplicates), each staffed by 2 clinicians (1 examined and 1
      measured). The relation between each range-of-motion and radiographic measure was
      determined. Data from each station were assessed separately. Only those
      regressions significant (P < .05) for paired stations were considered clinically
      significant. RESULTS: The alpha angle and head-neck offset measured on the frog
      leg lateral films were significantly correlated (all P < .01) to supine, sitting,
      and prone internal rotation for all stations. Correlation coefficients ranged
      from -0.59 to -0.35 for alpha angle and 0.42 to 0.57 for head-neck offset.
      Although 95% of the hips had at least 1 radiographic sign of FAI, pain was
      reported in only 8.5% and 2.3% during the impingement and FABER tests,
      respectively. CONCLUSIONS: Internal rotation correlates to radiographic measures
      of cam FAI in this cohort of collegiate football players. Football players with
      diminished internal rotation in whom hip pain develops should be evaluated for
      underlying cam FAI abnormalities. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 22999077
TI  - Giovanni Vitali: Discoverer of the paratympanic organ.
AB  - One-hundred years ago, the Italian anatomist Giovanni Vitali reported the
      discovery of the paratympanic organ, a sense organ in the middle ear of birds, in
      two issues of the Anatomischer Anzeiger (1911, 1912). In this minireview, we
      summarize Vitali's biography, and examine the scientific impact of his discovery
      of this sense organ. We also compile - for the first time - the entire
      bibliography of published papers on the paratympanic organ. Vitali described the
      ontogenetic development of this sense organ, examined its distribution among
      species, recognized its evolutionary relationship with the spiracular sense organ
      of fishes, and he developed the theory that it functions as a detector of changes
      in air pressure. He was the first to postulate that the paratympanic and
      spiracular sense organs were homologous organs that originate from homologous
      placodes - currently a hotly debated topic. His morphological work indicating the
      sensory nature of the PTO was validated by subsequent ultrastructural studies.
      Vitali's discovery of the paratympanic organ prompted his nomination for the
      Nobel Prize in 1934. Nevertheless, the paratympanic organ and the presumed
      barometric sense of hundreds of billions of living birds have failed to receive
      the recognition they deserve. Conclusive evidence of the function of the
      paratympanic organ remains a formidable challenge in vertebrate sensory
      physiology.

PMID- 22999078
TI  - Clinical course of preterm prelabor rupture of membranes in the era of
      prophylactic antibiotics.
AB  - BACKGROUND: Preterm prelabor rupture of membrane (PPROM) causes maternal and
      neonatal complications. Prophylactic antiobiotics were used in the management of
      PPROM. The objectives of this retrospective study were to compare clinical course
      and outcome of PPROM managed expectantly with prophylactic antibiotics and
      antenatal corticosteroids with those without prophylactic antibiotics and
      antenatal corticosteroids. RESULTS: A total of 170 cases of singleton pregnant
      women with gestational age between 28-34 weeks suffering from PROM during January
      1998 to December 2009 were included; 119 cases received prophylactic antibiotics
      and antenatal corticosteroids while 51 cases did not received prophylactic
      antibiotics and antenatal corticosteroids. Median latency period in the study
      group was significantly longer than in the control group (89.8 vs. 24.3 hours, P
      < 0.001). The percentage of patients who did not deliver within 48 hours and
      within 7 days in the study group were also significantly higher than in control
      group (64.7 vs. 31.4%, P < 0.001 and 29.4 vs. 7.8%, P = 0.002, respectively).
      Maternal infectious morbidity was comparable between groups (17.6% vs. 13.7%, P =
      0.52). Neonatal infectious morbidity was significantly lesser in study group than
      control group (21% vs. 35.3%, p = 0.04). CONCLUSIONS: Latency period of PPROM
      after using prophylactic antibiotics and antenatal corticosteroids increased
      while neonatal infectious morbidity was low. But maternal infectious morbidity
      was not increased. This retrospective study confirms the benefit of prophylactic
      antibiotics and antenatal corticosteroids in management of PPROM.

PMID- 22999079
TI  - HDL2 interferes with LDL association with arterial proteoglycans: a possible
      athero-protective effect.
AB  - OBJECTIVES: High levels of large HDL (HDL2) reduce cardiovascular disease risks
      apparently because it mediates reverse cholesterol transport, and it has anti
      inflammatory properties. Here we explored the mechanism behind an additional
      athero-protective HDL effect related to its capacity to interfere with formation
      of insoluble LDL-proteoglycans associations, a key step in LDL entrapment in the
      intima and in atherogenesis. METHODS AND RESULTS: We found that HDL2 levels from
      type 2 diabetes patients and controls are inversely correlated with complex
      formation between serum LDL and the arterial proteoglycans versican.
      Reconstitution experiments indicate that HDL2 was more efficacious inhibitor of
      the LDL-versican association than the smaller HDL3. This may explain why serum
      from patients with dyslipidemia of insulin resistance, with low levels of HDL2,
      have a higher capacity to form insoluble LDL-proteoglycan complex. ApoE
      enrichment of HDL2 and HDL3 or addition of copies of an apoE peptide with the
      proteoglycan-binding sequence of this apolipoprotein increased their inhibition
      of LDL-versican associations. CONCLUSIONS: The inhibitory effect of HDL2 and HDL3
      on LDL-versican associations was related to formation of apoE-mediated soluble
      HDL-versican complexes. We speculate that in the intima large, HDL2 subclasses,
      by forming reversible soluble associations with proteoglycans can compete with
      formation of irreversible LDL-proteoglycan aggregates. This can contribute to the
      HDL2 athero-protective effects. In the dyslipidemia of insulin resistance,
      associated with low levels of HDL2, this athero-protective property may be
      compromised.

PMID- 22999081
TI  - A clinical audit in a multidisciplinary care path for thoracic surgery: an
      instrument for continuous quality improvement.
AB  - BACKGROUND: Although it is advocated that (major) surgical procedures should be
      embedded in clinical pathways, the efficacy of such pathways is hardly ever
      systematically evaluated. The objective of our study was to assess the results of
      a multidisciplinary care path for patients undergoing thoracic cancer surgery,
      using a concurrent integrated prospective database. METHODS: From April 2006 to
      December 2008, 169 eligible patients, admitted for thoracic cancer surgery in our
      institute, gave informed consent to participate in this prospective study.
      Detailed clinical data concerning patient-, tumour-, treatment- and outcome
      characteristics were collected. For evaluation of pain and quality of life (QoL),
      visual analogue scale (VAS) and SF-36 were used respectively. Information
      retrieved on 94 patients operated in the baseline period (until November 2007)
      was used in multidisciplinary consensus meetings to develop a new care path.
      After the introduction of this care path (January 2008) data-collection continued
      to evaluate outcome using the data of 75 patients operated in the evaluation
      period (until December 2008). RESULTS: Data from the baseline period showed age
      (p=0.001), indication (p=0.03), postoperative pain (p<0.001) and complications
      (p<0.001) to be independently related to length of stay (LOS). Subsequently, the
      package of measures taken in the multidisciplinary care path were evaluated,
      showing significantly less postoperative pain (p=0.026) and a reduced length of
      hospital stay (p=0.014). In addition, a (trend towards) improvement in physical
      quality of life was observed 1 month (p=0.03) and 6 months (p=0.07)
      postoperatively. CONCLUSION: The use of a prospective database integrated in a
      clinical care path for thoracic cancer patients revealed important improvements
      of the care process determining short- and long-term outcome. There was a
      significant reduction in length of hospital stay, postoperative pain and loss of
      quality of life. Ongoing and multicentre collection of such data can provide
      surgeons with instruments to further improve quality of care.

PMID- 22999080
TI  - Adenocarcinoma of the lung with miliary brain and pulmonary metastases with
      echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase
      translocation treated with crizotinib: a case report.
AB  - Few descriptions of miliary brain metastases have been reported. We report the
      case of an adenocarcinoma of the lung associated with metachronous miliary brain
      and lung metastases with an echinoderm microtubule-associated protein like 4
      anaplastic lymphoma kinase (EML4-ALK) gene translocation. The patient was treated
      with crizotinib and showed a twelve-month progression-free survival. Clinicians
      should be attentive of the evolution of brain metastases with patients presenting
      EML4-ALK translocation.

PMID- 22999082
TI  - Lung cancer mortality in European women: trends and predictions.
AB  - Female lung cancer mortality increased by 50% between the mid 1960s and the early
      2000s in the European Union (EU). To monitor the current lung cancer epidemic in
      European women, we analyzed mortality trends in 33 European countries between
      1970 and 2009 and estimated rates for the year 2015 using data from the World
      Health Organization. Female lung cancer mortality has been increasing up to
      recent calendar years in most European countries, with the exceptions of Belarus,
      Russia, and Ukraine, with relatively low rates, and the UK, Iceland and Ireland,
      where high rates were reached in mid/late 1990s to leveled off thereafter. In the
      EU, female lung cancer mortality rates rose over the last decade from 11.3 to
      12.7/100,000 (+2.3% per year) at all ages and from 18.6 to 21.5/100,000 (+3.0%
      per year) in middle-age. A further increase is predicted, to reach 14/100,000
      women in 2015. Lung cancer mortality trends have been more favorable over the
      last decade in young women (20-44 years), particularly in the UK and other former
      high-risk countries from northern and central/eastern Europe, but also in France,
      Italy, and Spain where mortality in young women has been increasing up to the
      early 2000s. In the EU as a whole, mortality at age 20-44 years decreased from
      1.6 to 1.4/100,000 (-2.2% per year). Although the female lung cancer epidemic in
      Europe is still expanding, the epidemic may be controlled through the
      implementation of effective anti-tobacco measures, and it will probably never
      reach the top US rates.

PMID- 22999083
TI  - Robust superhydrophilic/hydrophobic surface based on self-aggregated Al2O3
      nanowires by single-step anodization and self-assembly method.
AB  - Superhydrophilic and superhydrophobic surfaces were studied with an eye to
      industrial applications and use as research tools. Conventional methods involve
      complex and time-consuming processes and cannot feasibly produce large-area three
      dimensional surfaces. Here, we report robust and large-area alumina nanowire
      structures with superhydrophobic or superhydrophilic properties, generated by an
      inexpensive single-step anodization process that can routinely create arbitrary
      three-dimensional shapes. This process is expected to open up diverse
      applications.

PMID- 22999084
TI  - [Treatment of stress urinary incontinence after prostate surgery: results of the
      artificial urinary sphincter after sub urethral sling failure].

PMID- 22999085
TI  - [Urinary incontinence and menopause].
AB  - PURPOSE: The aim of this review was to examine the relationship between menopause
      and urinary incontinence (UI). MATERIAL: Our work is based on a review of the
      literature on the epidemiology of UI in women and the effects of hormone therapy
      on symptoms of urinary leakage. A search of the Medline database between January
      2000 and April 2012 was performed by crossing the keywords "urinary incontinence,
      stress urinary incontinence (SUI), urge incontinence, over active bladder,
      menopause, estrogen therapy". RESULTS: Twenty-nine articles over the 482 articles
      were initialy selected. The UI was a common symptom during menopause, with a
      prevalence of 15 to 30% and an annual incidence of 5 to 10%. The association
      between UI and menopause was controversial. Indeed, although underpinned by
      pathophysiological mechanisms such as the sensitivity of tissues of the
      urogenital sinus to estrogen, the epidemiological data available were
      contradictory and should be interpreted, if possible, depending on the type of
      UI. Thus, it remained difficult to distinguish the effect of menopause of the
      aging. The effects of estrogen on IU differed depending on the route of
      administration and of the type of UI. Randomized trials showed that oral
      administration of estrogen after menopause increased the occurrence of UI or SUI.
      However a vaginal administration of estrogen improved urge urinary incontinence
      (UUI) and overactive bladder. CONCLUSION: The data of this review were consistent
      with the French and European guidelines.

PMID- 22999086
TI  - [Women's sexual life after spinal cord injury: psychological aspects].
AB  - AIM: Some changes were of a physical nature whereas other changes were of a
      psychological nature (feeling less attractive, having less self-confidence,
      difficulties to meet a partner). It would be risky to attempt a clear analysis of
      female sexuality outside its neurohormonal determinants and ability to relate to
      a wide anatomical area. The SCI women reported that the injury caused many
      changes in their sex life and affected many aspects of their sexuality
      negatively. METHODS: Review of the literature using the following keywords:
      spinal cord injury; sexuality; sexual life; woman; sexual arousal; libido;
      orgasm; psychology; psychogenic, sexual dysfunction. RESULTS: Women presenting
      with spinal cord injury face numerous challenges (denial of motor deficit,
      phantom limbs and the collapse of libido to which amenorrhea is added). After a
      period of rehabilitation (short or long), the automatic spinal reflexes and
      rehabilitation exercises (in order to recover ordinary life) force the women to
      challenge their own difficulties before recovering autonomy. The sensitivo-motor
      dissociation she discovers, forces her to confront the psychic divisions of
      desire and physical desire as she tries to find his sexuality. Hence, she
      attempts to get out of her emotional loneliness and be confronted with the risk
      of marital breakdown, problems sphincter and its dreams of pregnancy. CONCLUSION:
      Successful SCI rehabilitation requires a holistic approach, taking into account
      the patient's physical and psychological circumstances. Despite the presence of
      handicaps occurring following spinal cord injuries, a long way toward recovering
      self-esteem may enable her to find a different sexuality but flourished.

PMID- 22999087
TI  - [Contribution of investigations to the diagnosis of bladder outlet obstruction in
      women].
AB  - OBJECTIVE: To study the intrinsic diagnostic value of the exams performed to
      explore bladder outlet obstruction in women. METHODS: Review of literature
      (PubMed, Embase, Cochrane Database) using following keywords: female, bladder
      outlet obstruction, post-void residual, uroflowmetry, flow pattern, cystoscopy,
      MRI, retrograde cystography, bladder wall thickness, bladder trabeculation,
      urinary retention, voiding cystometry, pressure flow studies, electromyography.
      Among 2660 articles (animal and anatomical studies have been excluded), 40 have
      been selected because they focused on the evaluation of the intrinsic value of
      exams. RESULTS: The concomitant recording of bladder and abdominal pressure
      during voiding (pressure flow study) is useful to diagnose an hypocontractile
      detrusor, abdominal pressure efforts during voiding and obstruction (low voiding
      flow associated with a high bladder pressure). The reproducibility of pressure
      flow studies seems to be very good in the literature. Nomograms have been
      described to assess a possible obstruction, but some studies show no correlation
      between the severity of symptoms of bladder outlet obstruction and results on the
      main nomogram (nomogram of Blaivas). The measurement of the thickness of the
      bladder wall appears correctly correlated to the diagnosis of obstruction but
      measures vary significantly depending on the abdominal or vaginal
      ultrasonographic approach. CONCLUSION: In literature, only methods of measurement
      of maximum urinary flow rate and post-void residual volume have been extendedly
      studied.

PMID- 22999088
TI  - [Critical review of guidelines for female urinary incontinence diagnosis and
      treatment].
AB  - OBJECTIVES: To provide a critical review of the currently available guidelines on
      female urinary incontinence diagnosis and treatment. METHODS: Through a review of
      Medline, we identified the guidelines produced by five associations: French
      Urological Association (AFU), French National College of Gynaecologists and
      Obstetricians (CNGOF), American Urological Association (AUA), European
      Association of Urology (EAU) and International Urogynecological Association
      (IUGA). These guidelines were evaluated by the instrument provided by the
      Appraisal of Guidelines, Research and Evaluation. Then, the diagnosis and
      treatment recommendations were compared. RESULTS: The quality of guidelines were
      variable. Three of them (CNGOF, AFU, EAU) yielded to a score of more than 70. The
      rigor of development was not always optimal with a dilemma between evidence based
      medicine and the practice of experts. The best guidelines based on excellent meta
      analysis failed to consider the recent modifications of management. CONCLUSIONS:
      We found many differences in the quality of available guidelines.

PMID- 22999089
TI  - [Treatment of stress urinary incontinence after prostate surgery: results of the
      artificial urinary sphincter after suburethral sling failure].
AB  - OBJECTIVE: To determine whether the presence of a previously implanted
      suburethral sling for post-prostatic surgery incontinence influences the outcomes
      of subsequent AUS implantation. PATIENTS AND METHODS: A retrospective study
      comparing 15 patients who underwent AUS placement after suburethral sling failure
      between November 2004 and December 2009 to 15 patients who underwent AUS
      placement as first-line treatment during the same period. Demographic
      characteristics, preoperative assessment of urinary incontinence and technique of
      implantation of the AUS were similar in the both arms. A USP((r)) continence
      questionnaire was sent to patients by mail. Success was defined as a subjective
      improvement of the incontinence in patients using less than one pad per day.
      RESULTS: No perioperative incidents were noted in either arm. Mean operative
      time, the size of implanted cuffs, duration of catheterisation, length of
      hospital stay and postoperative complication rate, as well as the rate of
      surgical revision, were similar in both arms. The follow-up was slightly lower in
      the first arm (21 vs. 28.8 months, P=0.83). Stress incontinence and bladder
      overactivity scores of the USP((r)) questionnaire, as well as success rates (73.3
      vs. 80%, P=0.67), were equivalent in both arms. CONCLUSION: The results
      associated with the AUS procedure were not significantly different between men
      who had a suburethral male sling implanted before and those who had the AUS
      implanted as a first-line treatment.

PMID- 22999090
TI  - [Salvage therapy with artificial urinary sphincter after AdvanceTM male sling
      failure for post-prostatectomy incontinence: a first clinical experience].
AB  - OBJECTIVES: To assess the clinical outcome following artificial urinary sphincter
      (AUS) implantation after failure of AdvanceTM sub-urethral male sling for post
      prostatectomy incontinence (PPI). METHODS: A prospective evaluation was conducted
      about consecutive patients who received an AUS after failure of AdvanceTM therapy
      in one tertiary reference center. Evaluation included medical history, pad use
      and operative data (duration, cuff size, technical difficulties). Follow-up was
      scheduled at 1, 6, 12 months and yearly thereafter. Clinical outcome was
      evaluated by pad use, patient global impression of improvement (PGI-I) scale and
      assessment of side effects. Cure was defined as no pad usage. RESULTS: Twelve
      patients were included in this evaluation. Median follow-up was 20 months (12
      43). No patient was lost to follow-up. Four patients had a history of radiation
      therapy and all patients had mild or moderate PPI with previous failed AdvanceTM
      surgery. Median (range) operative time was 47 minutes (40-60). No technical
      problem occurred during AUS implantation. Hospital stay duration and
      catheterization duration were respectively 2 days and 24 hours in all but one
      case. At last follow-up, 10/12 patients (83%) were cured and fully satisfied. Two
      were improved, wearing only one pad per day. Postoperative complications were
      noted in two cases (17%) (one case of cutaneous erosion and one case of
      superficial iliac wound infection). CONCLUSIONS: AUS implantation is feasible in
      patients who have undergone AdvanceTM male sling implantation. Mid-term results
      of this procedure are comparable to those obtained after first line AUS
      implantation.

PMID- 22999091
TI  - [Predictive value of the penile cuff-test for the assessment of bladder outlet
      obstruction in men].
AB  - PURPOSE: To assess the diagnostic performances and the acceptability of the
      penile cuff test (PCT) which is a non invasive method for the evaluation of
      bladder outlet obstruction (BOO), in comparison with the pressure flow study
      (PFS), the actual gold-standard. MATERIAL: Monocentric prospective study
      comparing the following subsets: "obstructed", "not obstructed" or "equivocal",
      deduced from PFS vs PCT, in 30 consecutive patients presenting with lower urinary
      tract symptoms. For the PCT, a cuff placed around the penis inflated
      automatically during the micturition, until flow rate interruption. The
      interruption cuff pressure revealed the isovolumetric bladder pressure (Pcuff
      int). The data collected - Pcuff-int and maximum flow rate - were automatically
      reported on ICS modified nomogram. RESULTS: With the PFS, 11 patients (39%) were
      classified "obstructed", six patients (22%) "non-obstructed" and 11 patients
      (39%) "equivocal". In 61% cases, the patient was classified in the same category
      by both techniques. The "obstructed positive predictive value" of the PCT was 82%
      and the "non-obstructed-equivocal negative predictive value" was 88%. The median
      acceptability visual analogic scale score was 1/10 (0-3) for the PCT whereas it
      was 5/10 (2-10) for the PFS. This difference was statistically significant
      (p=0.004). CONCLUSION: The PCT was a reliable non-invasive tool for the diagnosis
      of BOO in male, in comparison with PFS. The predictive values of the PCT were
      relevant and its tolerance was better than PFS.

PMID- 22999092
TI  - [Sexual function before surgery for pelvic organ prolapse].
AB  - AIM: The aim of our study was to assess the link between pelvic organ prolapse
      (POP) characteristics and sexual well-being using validated tools. MATERIAL: A
      prospective analysis was carried out in 148 women with a POP. The degree of
      prolapse was measured by using the Pelvic Organ Prolapse Quantification (POPQ).
      Pelvic Floor Distress Inventory (PFDI-20) questionnaire score was used to
      estimate the severity of symptoms. Pelvic Organ Prolapse Urinary Incontinence
      Sexual Questionnaire short form (PISQ-12) scores determined sexual function
      level. RESULTS: No correlation was found concerning the global sexual function
      score and the POP stage (P=0.24). Pelvic and urinary symptoms were associated
      with a decrease in sexual function score (P=0.04 and P=0.002). Defecation
      symptoms were correlated with decreased sexual satisfaction (P <= 0.05) and were
      associated with premature ejaculation (P <= 0.05). Urinary symptoms were
      associated with dyspareunia (P <= 0.01), avoidance of sexual activities (P <=
      0.05), negative emotions during intercourse (P <= 0.01) and decreased sexual
      excitement (P <= 0.05). Pelvic symptoms were significantly tied to avoidance of
      sexual activities (P <= 0.01), dyspareunia (P <= 0.05) and a poorer orgasm
      quality (P <= 0.05). CONCLUSION: The degree of pelvic organ prolapse was not
      statistically associated with sexual function. However, urinary, pelvic and
      defecatory (ano-rectal) symptoms were associated with a decrease in the couple's
      sexual well-being.

PMID- 22999093
TI  - Management of kyphoscoliosis patients with respiratory failure in the intensive
      care unit and during long term follow up.
AB  - BACKGROUND: We aimed to evaluate the ICU management and long-term outcomes of
      kyphoscoliosis patients with respiratory failure. METHODS: A retrospective
      observational cohort study was performed in a respiratory ICU and outpatient
      clinic from 2002-2011. We enrolled all kyphoscoliosis patients admitted to the
      ICU and followed-up at regular intervals after discharge. Reasons for acute
      respiratory failure (ARF), ICU data, mortality, length of ICU stay and outpatient
      clinic data, non-invasive ventilation (NIV) device settings, and compliance were
      recorded. NIV failure in the ICU and the long term effect of NIV on pulmonary
      performance were analyzed. RESULTS: Sixty-two consecutive ICU kyphoscoliosis
      patients with ARF were enrolled in the study. NIV was initially applied to 55
      patients, 11 (20%) patients were intubated, and the majority had sepsis and
      septic shock (p < 0.001). Mortality in the ICU was 14.5% (n = 9), reduced pH,
      IMV, and sepsis/septic shock were significantly higher in the non-survivors (p
      values 0.02, 0.02, 0.028, 0.012 respectively). Among 46 patients attending the
      outpatient clinic, 17 were lost to follow up and six were died. The six minute
      walk distance was significantly increased in the final follow up (306 m versus
      419 m, p < 0.001). CONCLUSIONS: We strongly discourage the use of NIV in the case
      of septic shock in ICU kyphoscoliosis patients with ARF. Pulmonary performance
      improved with NIV during long term follow up.

PMID- 22999094
TI  - The increasing prevalence of HIV-1 subtype C in Southern Brazil and its
      dispersion through the continent.
AB  - The HIV-1 has evolved swiftly and the scenario of HIV-1 genetic diversity is
      constantly changing. In South America, recombinant forms of subtypes B, F1, and
      BF1 have historically driven the HIV-1 epidemic. In recent years, however,
      infection with subtype C has gained prominence as its prevalence increased in
      Southern Brazil as well as neighboring countries. Current studies point to a
      single introduction of closely related strains as the beginning of the Brazilian
      subtype C epidemic. However, the place of origin of these strains, date, and
      route of introduction are under continuous debate as well as the clinical
      outcomes of the emergence of subtype C. Therefore, this paper reviews the history
      of the HIV-1 subtype C in Brazil, particularly in the Southern region, covering
      its demographic and evolutionary history and the possible implications to the
      Brazilian AIDS epidemic as well as to neighboring countries.

PMID- 22999096
TI  - Serotype-specific differences in inhibition of reovirus infectivity by human-milk
      glycans are determined by viral attachment protein sigma1.
AB  - Human milk contains many bioactive components, including secretory IgA,
      oligosaccharides, and milk-associated proteins. We assessed the antiviral effects
      of several components of milk against mammalian reoviruses. We found that
      glucocerebroside (GCB) inhibited the infectivity of reovirus strain type 1 Lang
      (T1L), whereas gangliosides GD3 and GM3 and 3'-sialyllactose (3SL) inhibited the
      infectivity of reovirus strain type 3 Dearing (T3D). Agglutination of
      erythrocytes mediated by T1L and T3D was inhibited by GD3, GM3, and bovine
      lactoferrin. Additionally, alpha-sialic acid, 3SL, 6'-sialyllactose, sialic acid,
      human lactoferrin, osteopontin, and alpha-lactalbumin inhibited hemagglutination
      mediated by T3D. Using single-gene reassortant viruses, we found that serotype
      specific differences segregate with the gene encoding the viral attachment
      protein. Furthermore, GD3, GM3, and 3SL inhibit T3D infectivity by blocking
      binding to host cells, whereas GCB inhibits T1L infectivity post-attachment.
      These results enhance an understanding of reovirus cell attachment and define a
      mechanism for the antimicrobial activity of human milk.

PMID- 22999095
TI  - Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological
      impairment.
AB  - Standard methods used to estimate HIV-1 population diversity are often resource
      intensive (e.g., single genome amplification, clonal amplification and
      pyrosequencing) and not well suited for large study cohorts. Additional
      approaches are needed to address the relationships between intraindividual HIV-1
      genetic diversity and 2 disease. With a small cohort of individuals, we validated
      three methods for measuring diversity: Shannon entropy and average pairwise
      distance (APD) using single genome sequences, and counts of mixed bases (i.e.
      ambiguous nucleotides) from population based sequences. In a large cohort, we
      then used the mixed base approach to determine associations between measure HIV-1
      diversity and HIV associated disease. Normalized counts of mixed bases correlated
      with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid
      level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who
      underwent neuropsychological and clinical assessments (n=187), increased HIV-1
      population diversity was associated with both a diagnosis of AIDS and
      neuropsychological impairment.

PMID- 22999097
TI  - Orthopoxvirus species and strain differences in cell entry.
AB  - Vaccinia virus (VACV) enters cells by a low pH endosomal route or by direct
      fusion with the plasma membrane. We previously found differences in entry
      properties of several VACV strains: entry of WR was enhanced by low pH, reduced
      by bafilomycin A1 and relatively unaffected by heparin, whereas entry of IHD-J,
      Copenhagen and Elstree were oppositely affected. Since binding and entry modes
      may have been selected by specific conditions of in vitro propagation, we now
      examined the properties of three distinct, recently isolated cowpox viruses and a
      monkeypox virus as well as additional VACV and cowpox virus strains. The recent
      isolates were more similar to WR than to other VACV strains, underscoring the
      biological importance of endosomal entry by orthopoxviruses. Sequence
      comparisons, gene deletions and gene swapping experiments indicated that viral
      determinants, other than or in addition to the A26 and A25 "fusion-suppressor"
      proteins, impact entry properties.

PMID- 22999098
TI  - Effects of kinesiotherapy, ultrasound and electrotherapy in management of
      bilateral knee osteoarthritis: prospective clinical trial.
AB  - BACKGROUND: Although recent advances in knee osteoarthritis (OA) treatment and
      evaluation were achieved, to the best of our knowledge, few studies have
      evaluated the longitudinal effect of therapeutic modalities on the functional
      exercise capacity of patients with knee OA. The purpose was to investigate the
      effects of kinesiotherapy and electrotherapy on functional exercise capacity,
      evaluated using the six-minute walk test (6-MWT) in patients with bilateral knee
      OA. Secondary measurements included range of motion (ROM), severity of knee pain
      (VAS), and a measure of perceived health and physical function, evaluated using
      the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index.
      METHODS: A total of 40 women with bilateral knee OA were assigned to three
      groups: kinesiotherapy (KIN, n = 16), transcutaneous electrical nerve stimulation
      (TENS, n = 12), or ultrasound (US, n = 10). The groups underwent 12 weeks of
      intervention twice per week. The participants were subjected to the 6-MWT, ROM,
      VAS and WOMAC index. These tests were performed before and after the
      intervention. The study was focused on outpatients and was carried out at
      Universidade Estadual de Campinas, Brazil. RESULTS: At follow-up, the KIN and US
      groups had significantly higher 6-MWT distances (19.8 +/- 21.7 and 14.1 +/-
      22.5%, respectively) compared with their respective pre-intervention values. All
      treatments were effective for reducing pain and improving the WOMAC index.
      CONCLUSIONS: We demonstrated that the 6-MWT is a tool that can be used to
      evaluate improvements in the functional exercise capacity of patients submitted
      to a clinical intervention.

PMID- 22999099
TI  - Relationship of teicoplanin MICs to treatment failure in teicoplanin-treated
      patients with methicillin-resistant Staphylococcus aureus pneumonia.
AB  - BACKGROUND/PURPOSE: The objective of this study was to determine the predictive
      value of teicoplanin minimal inhibitory concentrations (MICs) for treatment
      failure among patients with methicillin-resistant Staphylococcus aureus (MRSA)
      pneumonia. METHODS: In this study, all patients with >=1 tracheal aspirates or
      sputum cultures positive for MRSA admitted to the hospital between April 2011 and
      September 2011 were reviewed. We enrolled patients who are >=18 years of age,
      with a diagnosis of pneumonia, and with a receipt of teicoplanin therapy
      throughout the course. The relationship between teicoplanin Etest MICs and
      treatment outcomes of MRSA pneumonia was analyzed to identify the breakpoint of
      teicoplanin MICs influencing treatment outcomes. RESULTS: Of the 80 patients
      enrolled, 31 had a lower teicoplanin MIC level (<2.0 mg/L) and 49 had a higher
      MIC level (>=2.0 mg/L) for MRSA. The lower MIC group had a higher clinical
      resolution rate in 14 days [24 (77.4%) vs. 23 (46.9%), p = 0.007] and a lower
      treatment failure rate at the end of teicoplanin treatment [4 (12.9%) vs. 18
      (36.7%), p = 0.020]. A comparison between the treatment success and failure
      groups showed that the former had a longer duration of teicoplanin use (18.76 +/-
      10.34vs.12.41 +/- 5.65 days; p = 0.014). Results of a multivariate analysis
      showed that teicoplanin MICs >= 2.0 mg/Land shorter duration of teicoplanin
      therapy were independent risk factors for treatment failure. CONCLUSION: A higher
      teicoplanin MIC value (>=2.0 mg/L) may predict the treatment failure among
      patients with teicoplanin-treated MRSA pneumonia.

PMID- 22999100
TI  - A survey of Culicoides developmental sites on a farm in northern Spain, with a
      brief review of immature habitats of European species.
AB  - Culicoides species (Diptera: Ceratopogonidae) belonging to the Obsoletus and
      Pulicaris groups are considered to be the main vectors of bluetongue virus (BTV)
      in non Mediterranean Europe. Selected terrestrial microhabitats (n=17) on a farm
      in northern Spain were sampled repeatedly over a year-long period and
      characterized for use by Culicoides species for immature development. Concurrent
      use of CDC light traps showed the presence of 37 species and 66,575 specimens of
      adult Culicoides. A total of 28 species and 11,396 individuals emerged from
      laboratory-maintained soil samples. Culicoides obsoletus and Culicoides scoticus
      (pooled as Obsoletus complex) were particularly abundant (comprising 58.6% and
      74.5% of the total collections in light traps and emergence traps respectively).
      Potential key vectors of animal viruses (such as BTV) were found in two main
      terrestrial types of microhabitats. In the case of C. obsoletus, different types
      of manure (old and composted manure, manure mixed with organic matter, and fresh
      manure) produced most of the specimens. In contrast, larvae of C. scoticus and
      Culicoides lupicaris were associated with soil substantially comprised of rotting
      leaf litter that included the parasitic plant Lathraea clandestina. Several
      species, Culicoides festivipennis, Culicoides punctatus and Culicoides
      brunnicans, were very common in mud at pond margins. Indeed, pond microhabitats
      and runoff below barn rooflines supported the greatest species richness. In the
      pond habitat, 49.4% of Culicoides specimens emerged from mud at the water edge,
      as opposed to 50 cm above (32.4%) and 1 meter above waterline (18%). Similar
      species richness, but statistically significant differences in abundance, were
      observed among the four pond microhabitats. Overall, the majority of the
      specimens were found in the upper layer (0-3 cm), except in manure, where they
      preferred deeper layers (>6 cm). Maximum peaks of abundance occurred in both
      light traps and soil samples in summer months, whereas increased captures in
      autumn were noticed only in light traps. Both trapping systems failed to collect
      adult Culicoides midges in the coldest months of December, January and February.
      The literature on immature habitats of species suspected in BTV transmission in
      Europe, the Pulicaris group and particularly the Obsoletus group, is briefly
      reviewed.

PMID- 22999101
TI  - Issues regarding the proposed DSM-5 personality disorders in geriatric psychology
      and psychiatry.

PMID- 22999102
TI  - Diagnostic approach in optic neuropathy.
AB  - The diagnostic of optic neuropathy (ON) is a clinical diagnostic, relying on a
      detailed medical history, and a thorough clinical examination. In some cases, the
      attribution of the vision loss to a lesion of the optic nerve can be challenging,
      and further work-up is required to confirm the optic neuropathy. Once the
      diagnostic of optic neuropathy is stated, the pathophysiological mechanism of the
      ON has to be determined so that the appropriate therapeutic strategy can be
      initiated as promptly as possible. The diagnostic work-up must be as targeted as
      possible, oriented by the clinical examination. The different steps leading to
      the positive diagnostic of ON, and the etiologic work-up are detailed hereafter
      in order to achieve the most targeted work-up as possible. Differentials and
      current pitfalls are being reviewed.

PMID- 22999103
TI  - [Balint syndrome and spatial functions of the parietal lobe].
AB  - Balint's syndrome corresponds to the combination of optic ataxia, simultanagnosia
      and gaze apraxia. It generally results from a bilateral dysfunction of the
      posterior parietal cortex. Since its early descriptions the syndrome has been
      subject to many interpretations and controversies. In this article we will
      reconsider the current concept of Balint's syndrome. A first part will develop
      the clinical aspects, causes, description of symptoms, examination techniques and
      neuroanatomical correlations. In a second part, we will discuss how this syndrome
      can be included in the background of visual neurosciences, particularly through a
      visual attentional aspect. We will discuss the phenomenon of remapping and some
      recent data that may contribute to explain the pathophysiology of manifestations
      as optic ataxia, simultanagnosia or gaze apraxia.

PMID- 22999104
TI  - Four clinically utilized drugs were identified and validated for treatment of
      adrenocortical cancer using quantitative high-throughput screening.
AB  - BACKGROUND: Drug repurposing for cancer treatment is an emerging approach to
      discover clinically approved drugs that demonstrate antineoplastic effect. The
      effective therapeutics for patients with advanced adrenocortical carcinoma(ACC)
      are greatly needed. The objective of this study was to identify and validate
      drugs with antineoplastic effect in ACC cells using a novel quantitative high
      throughput drug screening (qHTS) technique. METHODS: A quantitative high
      throughput proliferation assay of 2,816 clinically approved drugs was performed
      in the NCI-H295R ACC cell line. We validated the antiproliferative effect of
      candidate compounds in NCI-H295R cells. Further validation was performed in 3
      dimensional multicellular aggregates (MCA) of NCI-H295R and SW-13 cell lines.
      RESULTS: We identified 79 active compounds against ACC cells; 21 had an efficacy
      >= 60% and IC50 <1 MUM. The top drug categories enriched were cardiotonic,
      antiseptic, and antineoplastic. We selected Bortezomib, ouabain, Methotrexate,
      pyrimethamine for validation. All had an antiproliferative effect in monolayer
      culture of NCI-H295R cells at clinical achievable serum level. Bortezomib and
      ouabain inhibited growth of MCA in both cell lines at a low concentration (10
      fold below IC50). Methotrexate inhibited growth and caused disintegration of MCA
      in both cell lines at concentrations well below the maximum serum level (10 to
      100 fold of IC50). Pyrimethamine caused growth inhibition in both cell lines at
      10 fold of IC50 concentration. CONCLUSIONS: qHTS of previously approved compounds
      is an effective and efficient method to identify anticancer drugs for a rare
      cancer such as ACC. We have validated the antineoplastic effect of Bortezomib,
      ouabain, Methotrexate and pyrimethamine, which could be translated into clinical
      trials in patients with locally advanced and/or metastatic ACC.

PMID- 22999106
TI  - [Late paraphrenia: an accidental finding].

PMID- 22999105
TI  - A comparison study of body dysmorphic disorder versus social phobia.
AB  - Body dysmorphic disorder (BDD) shares many characteristics with social phobia
      (SP), including high levels of social anxiety and avoidance, but to our knowledge
      no studies have directly compared these disorders' demographic and clinical
      features. Demographic and clinical features were compared in individuals with BDD
      (n=172), SP (n=644), and comorbid BDD/SP (n=125). SP participants had a
      significantly earlier age of onset and lower educational attainment than BDD
      participants. BDD participants were significantly less likely to ever be married
      than SP participants, had a greater likelihood of ever being psychiatrically
      hospitalized, and had significantly lower mean GAF scores than SP participants.
      The two groups had different comorbidity patterns, which included a greater
      likelihood for BDD participants to have comorbid obsessive-compulsive disorder
      (OCD) or an eating disorder, vs. a greater likelihood for SP participants to have
      a comorbid non-OCD anxiety disorder. The comorbid BDD/SP group had significantly
      greater morbidity across several domains than the SP only group, but not the BDD
      only group. In summary, although BDD and SP were similar across many demographic
      and clinical features, they had important differences. Future studies are needed
      to confirm these findings and address similarities and differences between these
      disorders across a broader range of variables.

PMID- 22999107
TI  - Multi-scale mechanical characterization of scaffolds for heart valve tissue
      engineering.
AB  - Electrospinning is a promising technology to produce scaffolds for cardiovascular
      tissue engineering. Each electrospun scaffold is characterized by a complex micro
      scale structure that is responsible for its macroscopic mechanical behavior. In
      this study, we focus on the development and the validation of a computational
      micro-scale model that takes into account the structural features of the
      electrospun material, and is suitable for studying the multi-scale scaffold
      mechanics. We show that the computational tool developed is able to describe and
      predict the mechanical behavior of electrospun scaffolds characterized by
      different microstructures. Moreover, we explore the global mechanical properties
      of valve-shaped scaffolds with different microstructural features, and compare
      the deformation of these scaffolds when submitted to diastolic pressures with a
      tissue engineered and a native valve. It is shown that a pronounced degree of
      anisotropy is necessary to reproduce the deformation patterns observed in the
      native heart valve.

PMID- 22999108
TI  - Prognostic factors for non-success in patients with sciatica and disc herniation.
AB  - BACKGROUND: Few studies have investigated prognostic factors for patients with
      sciatica, especially for patients treated without surgery. The aim of this study
      was to identify factors associated with non-success after 1 and 2 years of follow
      up and to test the prognostic value of surgical treatment for sciatica. METHODS:
      The study was a prospective multicentre observational study including 466
      patients with sciatica and lumbar disc herniation. Potential prognostic factors
      were sociodemographic characteristics, back pain history, kinesiophobia,
      emotional distress, pain, comorbidity and clinical examination findings. Study
      participation did not alter treatment considerations for the patients in the
      clinics. Patients reported on the questionnaires if surgery of the disc
      herniation had been performed. Uni- and multivariate logistic regression analyses
      were used to evaluate factors associated with non-success, defined as Maine
      Seattle Back Questionnaire score of >=5 (0-12) (primary outcome) and Sciatica
      Bothersomeness Index >=7 (0-24) (secondary outcome). RESULTS: Rates of non
      success were at 1 and 2 years 44% and 39% for the main outcome and 47% and 42%
      for the secondary outcome. Approximately 1/3 of the patients were treated
      surgically. For the main outcome variable, in the final multivariate model non
      success at 1 year was significantly associated with being male (OR 1.70 [95% CI;
      1.06 - 2.73]), smoker (2.06 [1.31 - 3.25]), more back pain (1.0 [1.01 - 1.02]),
      more comorbid subjective health complaints (1.09 [1.03 - 1.15]), reduced tendon
      reflex (1.62 [1.03 - 2.56]), and not treated surgically (2.97 [1.75 - 5.04]).
      Further, factors significantly associated with non-success at 2 years were
      duration of back problems >; 1 year (1.92 [1.11 - 3.32]), duration of sciatica >;
      3 months (2.30 [1.40 - 3.80]), more comorbid subjective health complaints (1.10
      [1.03 - 1.17]) and kinesiophobia (1.04 [1.00 - 1.08]). For the secondary outcome
      variable, in the final multivariate model, more comorbid subjective health
      complaints, more back pain, muscular weakness at clinical examination, and not
      treated surgically, were independent prognostic factors for non-success at both 1
      and 2 years. CONCLUSIONS: The results indicate that the prognosis for sciatica
      referred to secondary care is not that good and only slightly better after
      surgery and that comorbidity should be assessed in patients with sciatica. This
      calls for a broader assessment of patients with sciatica than the traditional
      clinical assessment in which mainly the physical symptoms and signs are
      investigated.

PMID- 22999109
TI  - Comments on the ESC guidelines on cardiovascular disease prevention (version
      2012). A report of the Task Force of the Clinical Practice Guidelines Committee
      of the Spanish Society of Cardiology.

PMID- 22999110
TI  - Comments on the ESC Guidelines for the diagnosis and treatment of acute and
      chronic heart failure 2012. A report of the Task Force of the Clinical Practice
      Guidelines Committee of the Spanish Society of Cardiology.

PMID- 22999111
TI  - Multimodality cardiac imaging of a double chambered right ventricle with
      intrapulmonary shunting: a case report.
AB  - BACKGROUND: Double chambered right ventricle (DCRV) is a relatively rare
      congenital heart disease, characterized by the abnormal division of the right
      ventricle into a high-pressure inlet and low-pressure outlet by anomalous muscle
      bundles. Extra-cardiac right-to-left shunts may present with clinical symptoms in
      adulthood and should be sought in patients with previous cavo-pulmonary shunt
      procedures. CASE PRESENTATION: We report a case of DCRV in a 29 year old
      Caucasian male presenting in adulthood with a right-to-left shunt secondary to
      venous collaterals, following cavopulmonary anastomosis for congenital pulmonary
      atresia and hypoplastic right ventricle. CONCLUSION: Multimodality cardiac
      imaging using echocardiography, cardiac CT, cardiac MRI and cardiac
      catheterization is often required for complete characterization of complex
      congenital heart anomalies in adulthood.

PMID- 22999112
TI  - [Role of hypofractionated radiotherapy in the treatment of prostate cancer: a
      review].
AB  - BACKGROUND: Radiotherapy of prostate cancers, over the last few years, has been
      an alternative choice to radical prostatectomy in the case of localised cancers
      as well as being the preferred treatment in both advanced localised cancers and
      those of the elderly. A conventional course of prostate radiotherapy consisting
      of four to five sessions a week, lasts between 7 and 8 weeks plus about one week
      of preparation. MATERIALS AND METHODS: A systematic review of the scientific
      literature based on Pubmed, along with an exhaustive review of randomised studies
      presented at international congresses, have made it possible to analyse the
      numerous therapeutic regimens available other than the conventional
      normofractioned one (i.e. with doses per session ranging between 1.8 and 2.2
      grays). RESULTS: Five randomised trials reported since 2005, plus several
      thousand patients treated by stereotaxic radiotherapy, have given rise to
      numerous scientific questions; these alternative hypofractioned courses (dose per
      fraction higher than 2.2 grays) have a potentially enhanced antitumoral
      efficacity along with the practical advantages of a shortened duration of
      radiotherapy. CONCLUSION: The aim of this analysis of the scientific literature
      on hypofractioning in prostate cancer radiotherapy is to gather all the
      scientific evidence we currently have at our disposal. Further mature results of
      future randomised trials will have to be examined before modifying current
      practice.

PMID- 22999113
TI  - [Kidney transplantation in obese recipients: review of the Transplantation
      Committee of the French Association of Urology].
AB  - INTRODUCTION: Transplantation Committee of the French Association of Urology
      (CTAFU) conducted a review of the complication of kidney transplantation in obese
      recipients. MATERIAL AND METHODS: A bibliographic research in French and English
      using Medline with the keywords "obesity", "body mass index", "kidney
      transplantation", "graft function", "survival", "wound complications", "graft
      rejection" and "graft survival" was performed. We limited the review for the last
      fifteen years because of the change in immunosuppressive treatment area. Only
      studies with more than 20 obese patients were selected. RESULTS: Wound or
      infectious postoperative complications and delayed graft function are more
      frequent in obese patients than in non-obese recipients. Similarly, transplant
      survival at 5 years is lower in obese patients. On the other hand, patient
      survival and acute rejection are the same between the two groups if recipient
      selection is carefully made, particularly with regard to heart complication.
      CONCLUSION: Kidney transplantation in obese patients is not an easy surgery with
      known complication. Obese patients will take time before transplantation to
      explain all the risk and a regular heart follow-up is crucial if we don't want to
      reduce patient survival. But obese survival is better if we proceed to kidney
      transplantation than if they stay on dialysis, arguing for a non-exclusion of the
      waiting list. So there is the need for a national study concerning obese patients
      on waiting list to enact future guidelines.

PMID- 22999114
TI  - [Prostatic Stromal Tumors of Uncertain Malignant Potential (STUMP): definition,
      pathology, prognosis and management].
AB  - Prostatic Stromal Tumors of Uncertain Malignant Potential (STUMP) are rare tumor
      of the prostate of mesenchymal origin, accounting, with sarcoma for 0.1-0.2% of
      all malignant prostatic tumours. They however require to be individualized, to
      differentiate it from a benign prostatic hyperplasia or a sarcoma of the
      prostate. The therapeutic management should be made keeping in mind the risk of
      degeneration towards a malignant shape. Although the appropriate treatment is
      unknown, radical prostatectomy seem to be the treatment of reference, especially
      for young patient or for extensive lesion.

PMID- 22999115
TI  - [Small renal masses: 10 years of treatment in a tertiary referral center in
      cancer research].
AB  - OBJECTIVES: To analyze the impact of preoperative clinical data that could
      influence the undertaking of small renal masses (size<4cm) and to direct patients
      towards surgery or observance or radiofrequency. PATIENTS AND METHODS: From
      January 2000 to December 2010, 253 small renal masses were included in a
      retrospective study. Renal masses less than 3cm were compared to the 3 to 4cm
      masses. Clinical data, pathological data and follow-up was noted prospectively on
      the database and we analyzed it according to the treatment done (surgery,
      radiofrequency or observation). RESULTS: Surgical treatment, radiofrequency and
      observation were performed for 214 (86.4%), 15 (5.9%), and 24 (9.5%) patients
      respectively. The treatments of the patients differed in the two groups (<3cm vs.
      3-4cm) and the appeal to radiofrequency and observation was more frequent for
      elder patients (>65years old) and for those whom performance status (ECOG status)
      greater or equal to 1. Cancer specific survival was not statistically different
      for the two groups (average: 87.5% after 5years, mean 33months follow-up, P=0.7).
      Independent risk factors of recurrence were Fuhrman grade, synchronous tumors,
      noddles invasion and metastatic progression. Positive surgical margins were not a
      risk factor of recurrence (P=0.6). CONCLUSION: Age and performance status are the
      two main clinical data, which influence the treatment for patients with small
      renal masses. Radiofrequency and observation were undertaken more regularly for
      elder and altered ones. The use of scales as Charlson Index or Lee scale could
      help to choose more easily according to global morbidity and mortality.

PMID- 22999116
TI  - [Should we consider a complementary treatment after a renal colic drained by an
      ureteral stent?].
AB  - PURPOSE: The aim of the study was to evaluate if only ureteral stent removing
      after complicated renal colic (RC) could prevent from complementary treatment
      (shock-wawe lithortripsy or ureteroscopy). PATIENTS AND METHODS: Data from 95
      patients, 39 women and 56 men, who had an ureteral stent for complicated RC from
      2005 to 2010 were retrospectively collected. Mean age was 46.4 +/- 17.2 years.
      After the initial management, another hospitalization was organized where
      patients had ureteral stent removing under local anesthesia, then an abdominal CT
      scan without injection and complementary treatment of ureteral stones (none or
      ESWL or ureteroscopy). Parameters studied were age, sex, stone size, location of
      calcul. Quantitative values were compared with Student's t test. Qualitative
      values were compared with the Chi(2). P<0.05 was considered statistically
      significant. RESULTS: Mean duration between the two hospitalizations were 1.58 +/
      1.84 months. Sixty-one patients (64.2%) had no more urolithiasis. In these
      patients, mean size of urolithiasis was 5.85 +/- 2.33 mm. Location of
      urolithiasis in distal, mild and proximal ureter was 77%, 3% and 20%
      respectively. Thirty-four patients (35.8%) had persistant lithiasis after CT
      scan. Location of stone in distal, mild and proximal ureter was 17.5%, 5.8% and
      76.7% respectively. CONCLUSION: After management of complicated renal colic by
      ureteral stent, 64% of patients had spontaneous elimination of stones after
      removing of ureteral stent, especially in women and pelvic ureter.

PMID- 22999117
TI  - [Radical cystectomy for urothelial bladder cancer: prognostic impact of lymph
      node metastasis and soft tissue surgical margins].
AB  - PURPOSE: To assess the association of soft tissue surgical margins (STSM) and/or
      lymph node metatstasis (pN+) with characteristics and outcomes of patients
      treated with radical cystectomy (RC) for urothelial carcinoma of the bladder
      (UCB). MATERIALS AND METHODS: We retrospectively collected the data of 242
      patients treated with RC and pelvic lymphadenectomy for UCB between January 2005
      and June 2009. Different parameters were studied: age, PSAt, pathological stage
      of cystectomy specimen (pT and pN), tumor grade, number (nb) of nodes (N) in
      lymphadenectomy, nb of metastatic nodes (nb N+), bigger diameter of N+,
      ganglionic density, nb of N with capsular ruptur, associated CIS, associated
      prostate cancer, follow-up, global and specific survival, date and etiology of
      death. RESULTS: Positive STSM were identified in 22 patients (9.1%) and lymph
      node metastasis in 59 (24.4%). pN+ status was significantly associated with lower
      global (GS) and specific survival (SS) (P<0.003). So was it for patients with
      positive STSM R+ with actuarial 3-year GS and SS respectively of 5% and 25%
      versus 35% and 43.9% no STSM (P<0.001). CONCLUSIONS: Positive soft tissue
      surgical margin and/or lymph node metatstasis on cystectomy specimen is a strong
      predictor of GS and SS from urothelial carcinoma of the bladder. So it is for
      capsular rupture, ganglionic density greater or equal to 0.10 and nb of N in
      lymphadenectomy less than 14 for pN+ patients.

PMID- 22999118
TI  - [Evolution of prostatic surgical interventions: analysis of French national
      coding database].
AB  - INTRODUCTION: Prostatic diseases are very important in urologist's practice. We
      wanted to study evolution of prostatic procedures using French national coding
      database. METHODS: We searched the Agence Technique d'Information sur
      l'Hospitalisation (ATIH) web server for prostatic procedures between 1997 and
      2011 for both private and public sectors. RESULTS: The procedures were more often
      performed in private sector (up to 70%). There was a sustained increase (+332%)
      of the number of prostatectomies between 1997 and 2007 (more than 27,000
      procedures), followed by a slight decrease. There is a rising use of laparoscopic
      approach from 35% in 2006 up to 58% in 2011. The use of brachytherapy and HIFU
      was marginal. Transurethral resection of the prostate number was stable between
      56,000 and 60,000 procedures a year (for cancer for less than 7%). Adenomectomies
      number decreased from 9832 to 7963 procedures a year. CONCLUSION: The most
      noticeable data were upon prostatectomies number, with a peak effect in 2007.
      Laparoscopic procedures were more and more frequent. TURP number was stable,
      whereas adenomectomies number decreased.

PMID- 22999119
TI  - [Repeat prostate biopsies following a first negative biopsy in a context of an
      elevated prostate specific antigen].
AB  - INTRODUCTION: An elevated PSA and a negative prostate biopsy (PB) can be a false
      negative PB that ignores a prostate cancer (PCa) or a false positive PSA not
      related to PCa. The objective of this study was to analyze a group of patients
      who had a negative first BP for a PSA superior to 4 ng/mL and at least one
      additional PB and to compare these cases with controls who had the diagnosis PCa
      from the first PB. METHODS: Retrospective single-center study comparing patients
      with an elevated PSA and repeat biopsy following a first negative PB and patients
      with PCa diagnosed from the first PB. RESULTS: The 63 cases were younger than the
      75 controls and had more often a normal digital rectal examination. Their
      prostate volume was larger and their number of PSA before the first PB lower:
      this corresponded to a lower PSA in the second (7/64), third (6/31), fourth (3/9)
      and sixth (1/1) PB. Among these cases with PCa, the length of core invaded by
      cancer and the total length of cancer of the entire PB were smaller than
      controls. In 76% of cases, the Gleason score among cases was 6 or less.
      CONCLUSION: PCa discovered on repeat biopsy had features of better prognosis than
      those of controls. We propose an algorithm for management of patients with
      elevated PSA and negative first PB.

PMID- 22999120
TI  - [The Martius flap in stress urinary incontinence treated by suburethral sling].
AB  - OBJECTIVE: Study of a series of patients treated with suburethral tapes using the
      Martius flap technique, for complications or in a preventive way, in order to
      determine its interest and morbidity. PATIENTS: Eleven female patients treated by
      suburethral tapes for stress urinary incontinence, for which we described the
      type of tapes used, their complications, the procedure including Martius flap and
      the outcomes. RESULTS: Indications of the Martius flap were: three tapes through
      bladder neck, one through urethra, one uro-vaginal fistula, four loss of
      substance of the vaginal wall, one peri-urethral fibrosis and one preventive use
      on irradiated pelvis. Complications were transient postoperative pain and one
      abscess of the greater lip. In our series, the Martius flap never cured stress
      urinary incontinence. The placement of a suburethral tape on a Martius flap is
      feasible but the adjustment is more difficult. CONCLUSION: The Martius flap is
      efficient in the treatment or prevention of suburethral tapes complications with
      low morbidity. It allows secondary placement of a suburethral tape with difficult
      adjustment.

PMID- 22999121
TI  - [Flexible cystoscopes: disinfection and microbiological surveillance practices
      among French urologists].
AB  - INTRODUCTION: According to the French regulatory authorities, the highest level
      of disinfection must be achieved for flexible cystoscopes, as they enter a
      sterile cavity, the current method being peracetic acid disinfection and sterile
      water terminal rinsing. MATERIAL AND METHODS: The concordance between regulations
      and the routine was researched using a self-administered questionnaire sent to
      all French urologists. RESULTS: Responses from 78 urology units, totalling 317
      urologists (26% response rate) were analysed. As a whole, 51.2% of centers
      followed all recommendations on disinfection. There was no microbiological
      surveillance in 16.6% of centers, although microbiological tests were performed
      in two out of three centers before using a new endoscope or when returning from
      maintenance. CONCLUSION: Improvements are needed, both in the disinfection
      process and the microbiological surveillance. Low temperature sterilization and
      the use of sterile disposable sheaths may represent an alternative.

PMID- 22999122
TI  - [Metastatic melanoma in upper urinary tract: three cases and literature review].
AB  - Melanoma is a slowly growing malignancy, with potential distant metastasis at
      various sites. In this article, we reported three original cases of melanoma
      metastases in the upper urinary tract, and we achieved a literature review.
      Symptoms are inconstant and non-specific (pain or haematuria). Nephroureterectomy
      is performed in the majority of cases. Even if this metastatic location remains
      uncommon, it should be timely detected in order to allow an appropriate
      management and to improve the prognostic of melanoma.

PMID- 22999124
TI  - Predictors of an increase in the number of cerebral microbleeds after a first
      ever stroke.

PMID- 22999126
TI  - Creating models that meet decision makers' needs: a US payer perspective.

PMID- 22999127
TI  - The view of a model user on the ISPOR-SMDM modeling good research task force
      report.

PMID- 22999128
TI  - Modeling good research practices--overview: a report of the ISPOR-SMDM Modeling
      Good Research Practices Task Force--1.
AB  - Models--mathematical frameworks that facilitate estimation of the consequences of
      health care decisions--have become essential tools for health technology
      assessment. Evolution of the methods since the first ISPOR Modeling Task Force
      reported in 2003 has led to a new Task Force, jointly convened with the Society
      for Medical Decision Making, and this series of seven articles presents the
      updated recommendations for best practices in conceptualizing models;
      implementing state-transition approaches, discrete event simulations, or dynamic
      transmission models; and dealing with uncertainty and validating and reporting
      models transparently. This overview article introduces the work of the Task
      Force, provides all the recommendations, and discusses some quandaries that
      require further elucidation. The audience for these articles includes those who
      build models, stakeholders who utilize their results, and, indeed, anyone
      concerned with the use of models to support decision making.

PMID- 22999129
TI  - Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research
      Practices Task Force--2.
AB  - The appropriate development of a model begins with understanding the problem that
      is being represented. The aim of this article was to provide a series of
      consensus-based best practices regarding the process of model conceptualization.
      For the purpose of this series of articles, we consider the development of models
      whose purpose is to inform medical decisions and health-related resource
      allocation questions. We specifically divide the conceptualization process into
      two distinct components: the conceptualization of the problem, which converts
      knowledge of the health care process or decision into a representation of the
      problem, followed by the conceptualization of the model itself, which matches the
      attributes and characteristics of a particular modeling type with the needs of
      the problem being represented. Recommendations are made regarding the structure
      of the modeling team, agreement on the statement of the problem, the structure,
      perspective, and target population of the model, and the interventions and
      outcomes represented. Best practices relating to the specific characteristics of
      model structure and which characteristics of the problem might be most easily
      represented in a specific modeling method are presented. Each section contains a
      number of recommendations that were iterated among the authors, as well as among
      the wider modeling taskforce, jointly set up by the International Society for
      Pharmacoeconomics and Outcomes Research and the Society for Medical Decision
      Making.

PMID- 22999130
TI  - State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research
      Practices Task Force--3.
AB  - State-transition modeling is an intuitive, flexible, and transparent approach of
      computer-based decision-analytic modeling including both Markov model cohort
      simulation and individual-based (first-order Monte Carlo) microsimulation.
      Conceptualizing a decision problem in terms of a set of (health) states and
      transitions among these states, state-transition modeling is one of the most
      widespread modeling techniques in clinical decision analysis, health technology
      assessment, and health-economic evaluation. State-transition models have been
      used in many different populations and diseases, and their applications range
      from personalized health care strategies to public health programs. Most
      frequently, state-transition models are used in the evaluation of risk factor
      interventions, screening, diagnostic procedures, treatment strategies, and
      disease management programs. The goal of this article was to provide consensus
      based guidelines for the application of state-transition models in the context of
      health care. We structured the best practice recommendations in the following
      sections: choice of model type (cohort vs. individual-level model), model
      structure, model parameters, analysis, reporting, and communication. In each of
      these sections, we give a brief description, address the issues that are of
      particular relevance to the application of state-transition models, give specific
      examples from the literature, and provide best practice recommendations for state
      transition modeling. These recommendations are directed both to modelers and to
      users of modeling results such as clinicians, clinical guideline developers,
      manufacturers, or policymakers.

PMID- 22999131
TI  - Modeling using discrete event simulation: a report of the ISPOR-SMDM Modeling
      Good Research Practices Task Force--4.
AB  - Discrete event simulation (DES) is a form of computer-based modeling that
      provides an intuitive and flexible approach to representing complex systems. It
      has been used in a wide range of health care applications. Most early
      applications involved analyses of systems with constrained resources, where the
      general aim was to improve the organization of delivered services. More recently,
      DES has increasingly been applied to evaluate specific technologies in the
      context of health technology assessment. The aim of this article was to provide
      consensus-based guidelines on the application of DES in a health care setting,
      covering the range of issues to which DES can be applied. The article works
      through the different stages of the modeling process: structural development,
      parameter estimation, model implementation, model analysis, and representation
      and reporting. For each stage, a brief description is provided, followed by
      consideration of issues that are of particular relevance to the application of
      DES in a health care setting. Each section contains a number of best practice
      recommendations that were iterated among the authors, as well as among the wider
      modeling task force.

PMID- 22999132
TI  - Dynamic transmission modeling: a report of the ISPOR-SMDM Modeling Good Research
      Practices Task Force--5.
AB  - The transmissible nature of communicable diseases is what sets them apart from
      other diseases modeled by health economists. The probability of a susceptible
      individual becoming infected at any one point in time (the force of infection) is
      related to the number of infectious individuals in the population, will change
      over time, and will feed back into the future force of infection. These nonlinear
      interactions produce transmission dynamics that require specific consideration
      when modeling an intervention that has an impact on the transmission of a
      pathogen. Best practices for designing and building these models are set out in
      this article.

PMID- 22999133
TI  - Model parameter estimation and uncertainty: a report of the ISPOR-SMDM Modeling
      Good Research Practices Task Force--6.
AB  - A model's purpose is to inform medical decisions and health care resource
      allocation. Modelers employ quantitative methods to structure the clinical,
      epidemiological, and economic evidence base and gain qualitative insight to
      assist decision makers in making better decisions. From a policy perspective, the
      value of a model-based analysis lies not simply in its ability to generate a
      precise point estimate for a specific outcome but also in the systematic
      examination and responsible reporting of uncertainty surrounding this outcome and
      the ultimate decision being addressed. Different concepts relating to uncertainty
      in decision modeling are explored. Stochastic (first-order) uncertainty is
      distinguished from both parameter (second-order) uncertainty and from
      heterogeneity, with structural uncertainty relating to the model itself forming
      another level of uncertainty to consider. The article argues that the estimation
      of point estimates and uncertainty in parameters is part of a single process and
      explores the link between parameter uncertainty through to decision uncertainty
      and the relationship to value of information analysis. The article also makes
      extensive recommendations around the reporting of uncertainty, in terms of both
      deterministic sensitivity analysis techniques and probabilistic methods. Expected
      value of perfect information is argued to be the most appropriate presentational
      technique, alongside cost-effectiveness acceptability curves, for representing
      decision uncertainty from probabilistic analysis.

PMID- 22999134
TI  - Model transparency and validation: a report of the ISPOR-SMDM Modeling Good
      Research Practices Task Force--7.
AB  - Trust and confidence are critical to the success of health care models. There are
      two main methods for achieving this: transparency (people can see how the model
      is built) and validation (how well the model reproduces reality). This report
      describes recommendations for achieving transparency and validation developed by
      a taskforce appointed by the International Society for Pharmacoeconomics and
      Outcomes Research and the Society for Medical Decision Making. Recommendations
      were developed iteratively by the authors. A nontechnical description--including
      model type, intended applications, funding sources, structure, intended uses,
      inputs, outputs, other components that determine function, and their
      relationships, data sources, validation methods, results, and limitations--should
      be made available to anyone. Technical documentation, written in sufficient
      detail to enable a reader with necessary expertise to evaluate the model and
      potentially reproduce it, should be made available openly or under agreements
      that protect intellectual property, at the discretion of the modelers. Validation
      involves face validity (wherein experts evaluate model structure, data sources,
      assumptions, and results), verification or internal validity (check accuracy of
      coding), cross validity (comparison of results with other models analyzing the
      same problem), external validity (comparing model results with real-world
      results), and predictive validity (comparing model results with prospectively
      observed events). The last two are the strongest form of validation. Each section
      of this article contains a number of recommendations that were iterated among the
      authors, as well as among the wider modeling taskforce, jointly set up by the
      International Society for Pharmacoeconomics and Outcomes Research and the Society
      for Medical Decision Making.

PMID- 22999135
TI  - Dementia care in the general practice setting: a cluster randomized trial on the
      effectiveness and cost impact of three management strategies.
AB  - OBJECTIVE: To compare a complex nondrug intervention including actively
      approaching counseling and caregiver support groups with differing intensity
      against usual care with respect to time to institutionalization in patients with
      dementia. METHODS: Within this three-armed cluster-randomized controlled trial,
      390 community-dwelling patients aged 65 years or older with physician-diagnosed
      mild to moderate dementia and their caregivers were enrolled via 129 general
      practitioners in Middle Franconia, Germany. The intervention included general
      practitioners' training in dementia care and their recommendation of support
      groups and actively approaching caregiver counseling. Primary study end point was
      time to institutionalization over 2 years. In addition, long-term intervention
      effects were assessed over a time horizon of 4 years. Secondary end points
      included cognitive functioning, (instrumental) activities of daily living, burden
      of caregiving, and health-related quality of life after 2 years. Frailty models
      with strict intention-to-treat approach and mixed linear models were applied to
      account for cluster randomization. Health care costs were assessed from the
      societal perspective. RESULTS: After 2 (4) years, 12% (24%) of the patients were
      institutionalized and another 21% (35%) died before institutionalization. No
      significant differences between study groups were observed with respect to time
      to institutionalization after 2 and 4 years (P 0.25 and 0.71, respectively).
      Secondary end points deteriorated, but differences were not significant between
      study groups. Almost 80% of the health care costs were due to informal care.
      Total annual costs amounted to more than ?47,000 per patient and did not differ
      between study arms. CONCLUSION: The intervention showed no effects on time to
      institutionalization and secondary outcomes.

PMID- 22999136
TI  - Development of a decision-analytic model for the application of STR-based
      provenance testing of transrectal prostate biopsy specimens.
AB  - BACKGROUND: The diagnostic algorithm for most cancers includes the assessment of
      a tissue specimen by a surgical pathologist, but if specimen provenance is
      uncertain, the diagnostic and therapeutic process carries significant risk to the
      patient. Over the last decade, short tandem repeat (STR) analysis has emerged as
      a DNA-based method with clinical applicability for specimen identity testing
      (also known as specimen provenance testing). Although the clinical utility of
      identity testing using STR-based analysis has been demonstrated in many studies,
      its economic value has not been established. METHODS: We developed a decision
      analytic model of the application of STR-based provenance testing of transrectal
      prostate biopsy specimens obtained as part of routine clinical care to rule out
      the presence of adenocarcinoma of the prostate, as compared with no STR-based
      testing. Using parameter values drawn from the published literature, the cost
      effectiveness of STR-based testing was quantified by calculating the incremental
      cost-effectiveness ratio per quality-adjusted life-year gained. RESULTS: In
      comparison to the current standard practice of no identity testing, identity
      testing by STR-based analysis has an incremental cost-effectiveness ratio of
      $65,570 per quality-adjusted life-year gained at a testing cost of $618 per
      person. At a cost of $515 per person, identity testing would meet the
      conservative standard of $50,000 per quality-adjusted life-year. At a test cost
      of $290 per person, identity testing would be cost saving. CONCLUSION: Given the
      rapidly declining pricing of STR-based identity testing, it is likely that
      testing to confirm the identity of positive prostate biopsy samples will be a
      cost-effective method for preventing treatment errors stemming from
      misidentification. Studies to formally establish the frequency of specimen
      provenance errors in routine clinical practice would therefore seem justified.

PMID- 22999137
TI  - Costs of adverse drug events in German hospitals--a microcosting study.
AB  - OBJECTIVE: In Germany, only limited data are available to quantify the
      attributable resource utilization associated with adverse drug events (ADEs). The
      aim of this study was twofold: first, to calculate the direct treatment costs
      associated with ADEs leading to hospitalization and, second, to derive the excess
      costs and extra hospital days attributable to ADEs of inpatient treatments in
      selected German hospitals. METHODS: This was a retrospective and medical record
      based study performed from the hospitals' perspective based on administrative
      accounting data from three hospitals (49,462 patients) in Germany. Total
      treatment costs ("analysis 1") and excess costs (i.e., incremental resource
      utilization) between patients suffering from an ADE and those without ADEs were
      calculated by means of a propensity score-based matching algorithm ("analysis
      2"). RESULTS: Mean treatment costs ("analysis 1") of ADEs leading to
      hospitalization (n = 564) were ?1,978 +/- 2,036 (range ?191-18,147; median
      ?1,446; ?843-2,480 [Q1-Q3]). In analysis 2, the mean costs of inpatients
      suffering from an ADE (n = 1,891) as a concomitant disease or complication
      (?5,113 +/- 10,059; range ?179-246,288; median ?2,701; ?1,636-5,111 [Q1-Q3]) were
      significantly higher (?970; P < 0.0001) than those of non-ADE inpatients (?4,143
      +/- 6,968; range ?154-148,479; median ?2,387; ?1,432-4,701 [Q1-Q3]). Mean
      inpatient length of stay of ADE patients (12.7 +/- 17.2 days) and non-ADE
      patients (9.8 +/- 11.6 days) differed by 2.9 days (P < 0.0001). A nationwide
      extrapolation resulted in annual total treatment costs of ?1.058 billion.
      CONCLUSIONS: This is one of the first administrative data-based analyses
      calculating the economic consequences of ADEs in Germany. Further efforts are
      necessary to improve pharmacotherapy and relieve health care payers of
      preventable treatment costs.

PMID- 22999138
TI  - Cost-effectiveness of truncated therapy for hepatitis C based on rapid virologic
      response.
AB  - BACKGROUND: Shortened courses of treatment with pegylated interferon alfa and
      ribavirin for patients with hepatitis C virus infection who experience rapid
      virologic response can be effective in appropriately selected patients. The cost
      effectiveness of truncated therapy is not known. OBJECTIVE: To assess the cost
      effectiveness of response-guided therapy versus standard-duration therapy on the
      basis of best available evidence. METHODS: We developed a decision model for
      chronic hepatitis C virus infection representing two treatment strategies: 1)
      standard-duration therapy with pegylated interferon alfa and ribavirin for 48
      weeks in patients with genotype 1 or 4 and for 24 weeks in patients with genotype
      2 or 3 and 2) truncated therapy (i.e., 50% decrease in treatment duration) in
      patients with rapid virologic response. Patients for whom truncated therapy
      failed began standard-duration therapy guided by genotype. We used a Markov model
      to estimate lifetime costs and quality-adjusted life-years. RESULTS: In the base
      case analysis, mean lifetime costs were $46,623 +/- $2,483 with standard-duration
      therapy and $42,354 +/- $2,489 with truncated therapy. Mean lifetime quality
      adjusted life-years were similar between the groups (17.1 +/- 0.7 with standard
      therapy; 17.2 +/- 0.7 with truncated therapy). Across model simulations, the
      probability of truncated therapy being economically dominant (i.e., both cost
      saving and more effective) was 78.6%. The results were consistent when we
      stratified the data by genotype. In one-way sensitivity analyses, the results
      were sensitive only to changes in treatment efficacy. CONCLUSION: Truncated
      therapy based on rapid virologic response is likely to be cost saving for
      treatment-naive patients with chronic hepatitis C virus infection. Cost
      effectiveness varied with small changes in relative treatment efficacy.

PMID- 22999139
TI  - Orthopaedic trauma care in Haiti: a cost-effectiveness analysis of an innovative
      surgical residency program.
AB  - OBJECTIVE: In an effort to sustainably strengthen orthopaedic trauma care in
      Haiti, a 2-year Orthopaedic Trauma Care Specialist (OTCS) program for Haitian
      physicians has been developed. The program will provide focused training in
      orthopaedic trauma surgery and fracture care utilizing a train-the-trainer
      approach. The purpose of this analysis was to calculate the cost-effectiveness of
      the program relative to its potential to decrease disability in the Haitian
      population. METHODS: Using established methodology originally outlined in the
      World Health Organization's Global Burden of Disease project, a cost
      effectiveness analysis was performed for the OTCS program in Haiti. Costs and
      disability-adjusted life-years (DALYs) averted were estimated per fellow trained
      in the OTCS program by using a 20-year career time horizon. Probabilistic
      sensitivity analysis was used to simultaneously test the joint uncertainty of the
      cost and averted DALY estimates. A willingness-to-pay threshold of $1200 per DALY
      averted, equal to the gross domestic product per capita in Haiti, was selected on
      the basis of World Health Organization's definition of highly cost-effective
      health interventions. RESULTS: The OTCS program results in an incremental cost of
      $1,542,544 +/- $109,134 and 12,213 +/- 2,983 DALYs averted per fellow trained.
      The cost-effectiveness ratio of $133.97 +/- $34.71 per DALY averted is well below
      the threshold of $1200 per DALY averted. Furthermore, sensitivity analysis
      suggests that implementing the OTCS program is the economically preferred
      strategy with more than 95% probability at a willingness-to-pay threshold of $200
      per DALY averted and across the entire range of potential variable inputs.
      CONCLUSIONS: The current economic analysis suggests the OTCS program to be a
      highly cost-effective intervention. Probabilistic sensitivity analysis
      demonstrates that the conclusions remain stable even when considering the joint
      uncertainty of the cost and DALY estimates.

PMID- 22999140
TI  - Cost-effectiveness analysis of antiviral treatments for HBeAg-positive chronic
      hepatitis B in Canada.
AB  - OBJECTIVE: To conduct a cost-effectiveness analysis of currently available
      nucleos(t)ide antiviral treatments (lamivudine, telbivudine, entecavir, and
      tenofovir) for chronic hepatitis B in Canada. METHODS: Markov modeling was used
      to project the lifetime health benefits and costs associated with the antiviral
      treatments. The hypothetical patient population was hepatitis B e antigen
      positive chronic hepatitis B-infected patients aged 34 years. Quality-adjusted
      life-years were used as a measure of effectiveness. Long-term cumulative
      incidence of liver complications was also projected. Treatment effectiveness data
      were derived from the literature; meta-analysis was conducted when there was a
      large variance in reported effectiveness data. Costs were obtained from a cost
      analysis of treating chronic hepatitis B-related complications in Canada.
      Stochastic parameter uncertainty was examined in probabilistic sensitivity
      analysis by using second-order Monte Carlo simulation. Alternative modeling
      assumptions were assessed in scenario analysis. One-way sensitivity analysis was
      used to explore each parameter's impact on the uncertainty of the results.
      RESULTS: In the base-case analysis, telbivudine was dominated by entecavir and
      tenofovir. Tenofovir strictly dominated lamivudine, telbivudine, and entecavir.
      Over the 72-year period of the model, the expected life expectancy (undiscounted)
      of lamivudine, telbivudine, entecavir, and tenofovir was 35.71, 36.94, 37.65, and
      37.99 years, respectively. Tenofovir had the highest expected quality-adjusted
      life-years at 11.86 (discounted) in all comparisons. Scenario and sensitivity
      analyses proved the robustness of the base-case results. The projected 10-year
      cumulative incidence of cirrhosis and hepatocellular carcinoma was 11.40% and
      3.05%, respectively, for tenofovir, which is significantly lower than that for
      lamivudine. CONCLUSION: Tenofovir generated the best results compared with all
      other therapies under evaluation.

PMID- 22999141
TI  - Quality-of-life impact of sentinel lymph node biopsy versus axillary lymph node
      dissection in breast cancer patients.
AB  - OBJECTIVES: Controversy about quality-of-life (QOL) benefits of sentinel lymph
      node biopsy (SLNB) versus axillary lymph node dissection (ALND) in patients with
      breast cancer remains. Our aim was to compare the impact of SLNB and ALND on QOL
      and arm symptoms of patients with early breast cancer, using generic (short form
      36 health survey) and tumor site-specific (FACT-B+4) instruments. METHODS: This
      was a prospective longitudinal observational study of 93 patients (64 SLNB, 29
      ALND). Patients were evaluated presurgery and 1, 6, and 12 months postsurgery.
      Generalized estimation equation models were constructed to assess the effect of
      treatment on QOL. The relative risks of edema, dysesthesia, and heaviness were
      calculated comparing ALND to SLND. RESULTS: Most patients presented T1 (67.7%)
      and underwent breast-conserving surgery (92.5%). At 12 months, the SLNB group
      presented deterioration on the FACT-B+4 Arm Scale (beta coefficient estimated a
      change of -1.6 score points; P < 0.01) while, compared with SLNB, the
      deterioration in the ALND group was almost 2 additional score points higher (P =
      0.009). FACT-B+4 global summary and short form 36 health survey did not show
      statistically significant differences between groups. Relative risk of
      dysesthesia and subjective edema was higher for the ALND group than for the SLNB
      group (1.97 and 2.11 at month 12; P < 0.01). CONCLUSION: These results confirm
      the benefit of SLNB due to its lower arm morbidity impact on QOL, compared with
      ALND. There are clinically relevant between-treatment differences in the Arm
      Scale of FACT-B+4, while there were no relevant differences in general well
      being, measured with the disease-specific FACT-B+4 and the generic short form 36
      health survey.

PMID- 22999142
TI  - Effect of acute bleeding on daily quality of life assessments in patients with
      congenital hemophilia with inhibitors and their families: observations from the
      dosing observational study in hemophilia.
AB  - INTRODUCTION: Quality-of-life (QOL) assessments in frequently bleeding patients
      with congenital hemophilia with inhibitors and their families are confounded by
      preexisting arthropathy and family circumstances. Periodic QOL assessments
      typically made on nonbleed days may not provide complete reflections of the
      burden on patients/families. AIM: To evaluate the impact of bleeding episodes on
      patients/caregivers/families and the association between monthly QOL scores and
      patients' average diary experiences. METHODS: Frequently bleeding inhibitor
      patients (>=four bleeds in 3 months), or their caregivers, provided daily
      assessment of EuroQol five-dimensional questionnaire and EuroQol five-dimensional
      questionnaire visual analogue scale, pain (11-point Likert scale), and family
      anxiety/stress/activity change over 3 to 6 months. QOL scores were stratified by
      bleed/nonbleed days. RESULTS: Patient QOL assessments were recorded by 37 of the
      39 enrolled patients/caregivers (3771 of 3777 eligible dairy days, 472 bleed/3299
      nonbleed days). Median (range) diary duration was 91 (66-180) days, with 8.2% (0%
      72.2%) bleed days. Mean health scores were significantly worse on bleed days than
      on nonbleed days (P < 0.0001 for all): EuroQol five-dimensional questionnaire
      index, 0.66 versus 0.82; visual analogue scale health, 69.7 versus 77.4; and pain
      score, 4.1 versus 1.8. Bleed days also had higher (P < 0.001) proportions of days
      with abnormalities in family anxiety/stress (42% vs. 30%) and family activity
      changes (34% vs. 21%). CONCLUSIONS: Assessing the impact of hemophilia with
      inhibitors on patient/family QOL typically includes periodic (likely nonbleed
      day) evaluations reflecting baseline abnormalities. Daily assessment, however,
      indicated that frequent acute bleeds impair QOL beyond patient's nonbleed day
      baseline. New approaches are required to assess the cumulative impact of frequent
      acute bleeds on patients and their families.

PMID- 22999143
TI  - The utility assessment method order influences measurement of parents' risk
      attitude.
AB  - BACKGROUND: Standard gamble (SG) and time trade-off (TTO) are two methods used
      for obtaining health utility values (utilities). Whether the order in which the
      methods are applied alters the relative utilities obtained by each method is
      unknown. OBJECTIVE: We sought to determine whether the order in which SG and TTO
      utilities were obtained affects the relative values of the utilities obtained by
      each technique. METHODS: Utilities were assessed for 29 health states from 4016
      parents by using SG and TTO. The assessment order was randomized by respondent.
      For analysis by health state, we calculated (SG - TTO) for each assessment and
      tested whether the SG - TTO difference was significantly different between the
      two groups (SG first and TTO first). For analysis by individual, we calculated a
      risk-posture coefficient, gamma, defined by the utility curve, SG = TTO(gamma).
      We predicted gamma through regression analysis with the covariates: child age,
      child sex, birth order, respondent age, respondent education level, and
      assessment method order. RESULTS: In 19 of 29 health states, the SG - TTO
      difference was significantly greater (more risk averse) when TTO was assessed
      first. In the regression analysis, "child age" and "assessment method order" were
      significant predictors of risk attitude. The risk posture coefficient gamma was
      higher (more risk-seeking) with increasing child age and in the SG-first
      respondents. CONCLUSION: The order in which the SG versus TTO method is used
      strongly influences the relative values of the utilities obtained.

PMID- 22999144
TI  - A comparison of preferences of targeted therapy for metastatic renal cell
      carcinoma between the patient group and health care professional group in South
      Korea.
AB  - OBJECTIVES: To evaluate the preferences of health care professional groups and
      patient groups with respect to efficacy, adverse events, and administration
      method for targeted agents of metastatic renal cell carcinoma. METHODS: A total
      of 485 respondents including cancer patients and health care professionals
      (medical oncologists, nurses, and pharmacists) were surveyed by using a discrete
      choice experiment in South Korea. Through a literature review and expert
      consultation, six attributes--progression-free survival, four adverse events
      (bone marrow suppression, hand-foot skin reaction, gastrointestinal perforation,
      and bleeding), and administration--were selected. This study employed the
      conditional logit regression model. RESULTS: The six attributes are statistically
      significant for the patient group and health care professional group. The two
      groups, however, present differences in progression-free survival, hand-foot skin
      reaction, gastrointestinal perforation, and administration. The relative
      importance of adverse events is greater for the patient group, while that of
      efficacy and administration is greater for the health professional group. For
      doctors, the relative importance of efficacy is as high as 31%, compared with 7%
      for the patient group. If progression-free survival is prolonged by 1 month, the
      acceptable level of bone marrow suppression is 1.3% for the patient group and
      9.6% for doctors and that of hand-foot skin reaction is 1.0% and 11.8%,
      respectively, for the patient group and doctors. CONCLUSIONS: This study
      demonstrates substantial differences in the preference for a targeted drug
      between the patient group and the health care professional group. Doctors prefer
      effective and orally administered drugs while patients show more reluctant
      attitudes about adverse events than do health care professionals.

PMID- 22999145
TI  - Matching-adjusted indirect comparisons: a new tool for timely comparative
      effectiveness research.
AB  - OBJECTIVE: In the absence of head-to-head randomized trials, indirect comparisons
      of treatments across separate trials can be performed. However, these analyses
      may be biased by cross-trial differences in patient populations, sensitivity to
      modeling assumptions, and differences in the definitions of outcome measures. The
      objective of this study was to demonstrate how incorporating individual patient
      data (IPD) from trials of one treatment into indirect comparisons can address
      several limitations that arise in analyses based only on aggregate data. METHODS:
      Matching-adjusted indirect comparisons (MAICs) use IPD from trials of one
      treatment to match baseline summary statistics reported from trials of another
      treatment. After matching, by using an approach similar to propensity score
      weighting, treatment outcomes are compared across balanced trial populations.
      This method is illustrated by reviewing published MAICs in different therapeutic
      areas. A novel analysis in attention deficit/hyperactivity disorder further
      demonstrates the applicability of the method. The strengths and limitations of
      MAICs are discussed in comparison to those of indirect comparisons that use only
      published aggregate data. RESULTS: Example applications were selected to
      illustrate how indirect comparisons based only on aggregate data can be limited
      by cross-trial differences in patient populations, differences in the definitions
      of outcome measures, and sensitivity to modeling assumptions. The use of IPD and
      MAIC is shown to address these limitations in the selected examples by reducing
      or removing the observed cross-trial differences. An important assumption of
      MAIC, as in any comparison of nonrandomized treatment groups, is that there are
      no unobserved cross-trial differences that could confound the comparison of
      outcomes. CONCLUSIONS: Indirect treatment comparisons can be limited by cross
      trial differences. By combining IPD with published aggregate data, MAIC can
      reduce observed cross-trial differences and provide decision makers with timely
      comparative evidence.

PMID- 22999146
TI  - FDA actions against health economic promotions, 2002-2011.
AB  - OBJECTIVE: To investigate Food and Drug Administration (FDA) regulatory actions
      against drug companies' health economic promotions from 2002 through 2011 to
      understand how frequently and in what circumstances the agency has considered
      such promotions false or misleading. METHODS: We reviewed all warning letters and
      notices of violation ("untitled letters") issued by the FDA's Division of Drug
      Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies
      from January 2002 through December 2011. We analyzed letters containing a
      violation related to "health economic promotion," defined according to one of
      several categories (e.g., implied claims of cost savings due to work productivity
      or economic claims containing unsupported statements about effectiveness or
      safety). We also collected information on factors such as the indication and type
      of media involved and whether the letter referenced Section 114 of the Food and
      Drug Administration Modernization Act. RESULTS: Of 291 DDMAC letters sent to
      pharmaceutical companies during the study period, 35 (12%) cited a health
      economic violation. The most common type of violation cited was an implied claim
      of cost savings due to work productivity or functioning (found in 20 letters) and
      economic claims containing unsubstantiated comparative claims of effectiveness,
      safety, or interchangeability (7 letters). The violations covered various
      indications, mostly commonly psychiatric disorders (6 letters) and pain (6
      letters). No DDMAC letter pertained to Food and Drug Administration Modernization
      Act Section 114. CONCLUSION: The FDA has cited inappropriate health economic
      promotions in roughly 12% of the letters issued by the DDMAC. The letters
      highlight drug companies' interest in promoting the value of their products and
      the FDA's concerns in certain cases about the lack of supporting evidence.

PMID- 22999147
TI  - Relative effectiveness assessment of pharmaceuticals: similarities and
      differences in 29 jurisdictions.
AB  - OBJECTIVE: Assessment of the effectiveness compared with alternative treatment(s)
      plays an important role in many jurisdictions in determining the reimbursement
      status of pharmaceuticals. This type of assessment is often referred to as a
      relative effectiveness assessment (REA) and is carried out by many jurisdictions.
      Increased sharing of information across jurisdictions may save costs and reduce
      duplication. The objective of this study was to explore the main similarities and
      differences in the major methodological aspects of REA in multiple jurisdictions.
      METHODS: Data were gathered with a standardized data extraction form by searching
      publicly available information and by eliciting information from representatives
      at relevant organizations. RESULTS: Of the initially included 35 jurisdictions,
      data were gathered for 29 jurisdictions. There seem to be substantial
      similarities on the choice of the comparator, the role of indirect comparisons,
      and preferred end points in REAs (except for the use of health state utilities).
      Jurisdictions, however, differ in whether effectiveness (usual circumstances of
      health care practice) is estimated in case no (comparative) effectiveness data
      are available and how this is done. CONCLUSION: Some important methodological
      aspects for REA are approached in a similar way in many jurisdictions, indicating
      that collaboration on assessments may be feasible. Enhanced collaboration in the
      development of methods and best practices for REA between jurisdictions will be a
      necessary first step. Important topics for developing best practice are indirect
      comparisons and how to handle the gap between efficacy and effectiveness data in
      case good quality comparative effectiveness data are not yet available at the
      time of reimbursement decisions.

PMID- 22999148
TI  - Multicriteria decision analysis for including health interventions in the
      universal health coverage benefit package in Thailand.
AB  - OBJECTIVES: Considering rising health expenditure on the one hand and increasing
      public expectations on the other hand, there is a need for explicit health care
      rationing to secure public acceptance of coverage decisions of health
      interventions. The National Health Security Office, the institute managing the
      Universal Coverage Scheme in Thailand, recently called for more rational,
      transparent, and fair decisions on the public reimbursement of health
      interventions. This article describes the application of multicriteria decision
      analysis (MCDA) to guide the coverage decisions on including health interventions
      in the Universal Coverage Scheme health benefit package in the period 2009-2010.
      METHODS: We described the MCDA priority-setting process through participatory
      observation and evaluated the rational, transparency, and fairness of the
      priority-setting process against the accountability for reasonableness framework.
      RESULTS: The MCDA was applied in four steps: 1) 17 interventions were nominated
      for assessment; 2) nine interventions were selected for further quantitative
      assessment on the basis of the following criteria: size of population affected by
      disease, severity of disease, effectiveness of health intervention, variation in
      practice, economic impact on household expenditure, and equity and social
      implications; 3) these interventions were then assessed in terms of cost
      effectiveness and budget impact; and 4) decision makers qualitatively appraised,
      deliberated, and reached consensus on which interventions should be adopted in
      the package. CONCLUSION: This project was carried out in a real-world context and
      has considerably contributed to the rational, transparent, and fair priority
      setting process through the application of MCDA. Although the present project has
      applied MCDA in the Thai context, MCDA is adaptable to other settings.

PMID- 22999149
TI  - Using health state utility values in models exploring the cost-effectiveness of
      health technologies.
AB  - BACKGROUND: To improve comparability of economic data used in decision making,
      some agencies recommend that a particular instrument should be used to measure
      health state utility values (HSUVs) used in decision-analytic models. The methods
      used to incorporate HSUVs in models, however, are often methodologically poor and
      lack consistency. Inconsistencies in the methodologies used will produce
      discrepancies in results, undermining policy decisions informed by cost per
      quality-adjusted life-years. OBJECTIVE: To provide an overview of the current
      evidence base relating to populating decision-analytic models with HSUVs.
      FINDINGS: Research exploring suitable methods to accurately reflect the baseline
      or counterfactual HSUVs in decision-analytic models is limited, and while one
      study suggested that general population data may be appropriate, guidance in this
      area is poor. Literature describing the appropriateness of different methods used
      to estimate HSUVs for combined conditions is growing, but there is currently no
      consensus on the most appropriate methodology. While exploratory analyses suggest
      that a statistical regression model might improve accuracy in predicted values,
      the models require validation and testing in external data sets. Until additional
      research has been conducted in this area, the current evidence suggests that the
      multiplicative method is the most appropriate technique. Uncertainty in the HSUVs
      used in decision-analytic models is rarely fully characterized in decision
      analytic models and is generally poorly reported. CONCLUSIONS: A substantial
      volume of research is required before definitive detailed evidence-based
      practical advice can be provided. As the methodologies used can make a
      substantial difference to the results generated from decision-analytic models,
      the differences and lack of clarity and guidance will continue to lead to
      inconsistencies in policy decision making.

PMID- 22999150
TI  - The inclusion of informal care in applied economic evaluation: a review.
AB  - OBJECTIVE: Theory and guidelines advocating the inclusion of informal care in
      economic evaluation have, in recent years, been accompanied by developments in
      the methods for capturing the costs and outcomes related to informal care. The
      objective of this study was to review applied economic evaluations to identify
      the methods used for, and implications of, including informal care in practice.
      METHODS: Searches of key databases were conducted to identify all full economic
      evaluations incorporating costs or outcomes relating to informal care.
      Information was extracted by using a standard template from all studies meeting
      the inclusion criteria. RESULTS: Thirty economic evaluations were identified that
      included informal care. Twenty-five of these studies costed carers' time input
      and 17 measured outcomes for carers. The reported cost-effectiveness of
      interventions was altered by including informal care, in some cases changing the
      key conclusions for health care funding. CONCLUSIONS: Theory and methods
      development around informal care are yet to significantly permeate the applied
      literature; however, the results suggest that some funding priorities may change
      if they were to do so. The development of 1) a reference case for including
      informal care; 2) sensitivity analysis for contentious issues; and 3) a statement
      for the reason for excluding informal care, if this is deemed appropriate, may
      help to improve the way that informal care is included in economic evaluations in
      the future.

PMID- 22999151
TI  - An evaluation framework for funding drugs for rare diseases.
AB  - OBJECTIVES: For rare diseases it may be difficult to generate data from
      randomized trials to support funding of a drug. Enzyme replacement therapies for
      diseases of inherited metabolic enzyme deficiency provide an example of this
      dilemma. The Ontario Public Drug Programs convened the Drugs for Rare Diseases
      Working Group to develop a policy for assessing these drugs. METHODS: The Drugs
      for Rare Diseases Working Group developed terms of reference expecting that the
      ideal policy product would be transparent and consistent and address unique
      aspects of the treatment of a specific rare condition while being adaptable to
      other dissimilar conditions. The perspective was that of a public payer
      addressing requests for funding generated for a specific drug, and included
      respect for the principles of "accountability for reasonableness" of Daniels and
      Sabin. RESULTS: A seven-step framework was developed and tested by using the case
      study of idursulfase for mucopolysaccharidosis II (Hunter disease). Estimation of
      clinical effectiveness was done by using decision modeling. The model developed
      informed funding recommendations and ultimately led to an agreement with the
      manufacturer allowing funding of idursulfase in Ontario. CONCLUSIONS: This policy
      framework attempts to address the policy challenges of funding drugs for rare
      diseases. The framework will be used to assess other drugs in future and will
      inevitably require modification with experience. It is hoped that it may be of
      value to other policymakers.

PMID- 22999152
TI  - Evaluating new health technologies and disease burden in developed countries.

PMID- 22999154
TI  - See it in 3D!: researchers examined structural links between the cardinal and
      uterosacral ligaments.

PMID- 22999155
TI  - Ureteral injury during vaginal mesh excision: role of prevention and treatment
      options.
AB  - Vaginal mesh kits are increasingly used in vaginal prolapse repair. Mesh erosion,
      infection, and pain may necessitate removal, which can lead to urinary tract
      injury. We describe 2 cases of ureteral injury at the time of mesh excision.
      Surgeons must recognize the possibility of ureteral injury and treatment
      modalities available.

PMID- 22999156
TI  - A framework for strategic investments in research to reduce the global burden of
      preterm birth.
AB  - Preterm birth and stillbirth are among the greatest health burdens associated
      with pregnancy and childbirth. Fifteen million babies are born preterm each year,
      causing about 1 million deaths annually and lifelong problems for many survivors;
      3 million stillbirths also occur annually. Worldwide, the number of women and
      children who die during pregnancy and childbirth exceeds the total number of
      births in the United States. New approaches could provide a greater understanding
      of prematurity, stillbirth, and maternal complications of pregnancy and
      childbirth. Integrated multidisciplinary investigations of the mother, fetus, and
      newborn in different contexts and populations could elucidate the biological
      pathways that result in adverse outcomes and how to prevent them. Descriptive
      research can determine the burden of disease, while more mechanistic discovery
      research could explore the physiology and pathophysiology of pregnancy and
      childbirth. Together, this research can lead to the development and delivery of
      new and much more effective interventions, even in low-resource settings. Recent
      surveys of researchers and funders reveal a striking lack of consensus regarding
      priority areas for research and the development of interventions. While
      researchers enumerate unanswered questions about pregnancy and childbirth, they
      lack consensus on priorities. Funders are equally uncertain about research and
      development projects that need to be undertaken, and many are hard-pressed to
      support research on the complex problems of pregnancy and childbirth given
      competing priorities. This lack of consensus provides an opportunity to engage
      with funders and researchers to recognize the importance of understanding healthy
      pregnancies and the consequences of adverse pregnancy outcomes. A strategic
      alliance of funders, researchers, nongovernmental organizations, the private
      sector, and others could organize a set of grand challenges centered on pregnancy
      and childbirth that could yield a substantial improvement in reproductive health.

PMID- 22999157
TI  - Transabdominal amnioinfusion for preterm premature rupture of membranes: a
      systematic review and metaanalysis of randomized and observational studies.
AB  - OBJECTIVE: The purpose of this study was to review systematically the efficacy of
      transabdominal amnioinfusion (TA) in early preterm premature rupture of membranes
      (PPROM). STUDY DESIGN: We conducted a literature search of EMBASE, MEDLINE, and
      ClinicalTrials.gov databases and identified studies in which TA was used in cases
      of proven PPROM and oligohydramnios. Risk of bias was assessed for observational
      studies and randomized controlled trials. Primary outcomes were latency period
      and perinatal mortality rates. RESULTS: Four observational studies (n = 147) and
      3 randomized controlled trials (n = 165) were eligible. Pooled latency period was
      14.4 (range, 8.2-20.6) and 11.41 (range -3.4 to 26.2) days longer in the TA group
      in the observational and the randomized controlled trials, respectively.
      Perinatal mortality rates were reduced among the treatment groups in both the
      observational studies (odds ratio, 0.12; 95% confidence interval, 0.02-0.61) and
      the randomized controlled trials (odds ratio, 0.33; 95% confidence interval, 0.10
      1.12). CONCLUSION: Serial TA for early PPROM may improve early PPROM-associated
      morbidity and mortality rates. Additional adequately powered randomized control
      trials are needed.

PMID- 22999158
TI  - Pregnancy-onset habitual snoring, gestational hypertension, and preeclampsia:
      prospective cohort study.
AB  - OBJECTIVE: This study aimed to prospectively examine the impact of chronic vs
      pregnancy-onset habitual snoring on gestational hypertension, preeclampsia, and
      gestational diabetes. STUDY DESIGN: Third-trimester pregnant women were recruited
      from a large, tertiary medical center from March 2007 through December 2010 and
      screened for the presence and duration of habitual snoring, as a known marker for
      sleep-disordered breathing. Clinical diagnoses of gestational hypertension,
      preeclampsia, and gestational diabetes were obtained. RESULTS: Of 1719 pregnant
      women, 34% reported snoring, with 25% reporting pregnancy-onset snoring. After
      adjusting for confounders, pregnancy-onset, but not chronic, snoring was
      independently associated with gestational hypertension (odds ratio, 2.36; 95%
      confidence interval, 1.48-3.77; P < .001) and preeclampsia (odds ratio, 1.59; 95%
      confidence interval, 1.06-2.37; P = .024) but not gestational diabetes.
      CONCLUSION: New-onset snoring during pregnancy is a strong risk factor for
      gestational hypertension and preeclampsia. In view of the significant morbidity
      and health care costs associated with hypertensive diseases of pregnancy, simple
      screening of pregnant women may have clinical utility.

PMID- 22999159
TI  - Ordered to isotropic morphology transition in pattern-directed dewetting of
      polymer thin films on substrates with different feature heights.
AB  - Controlled dewetting of a thin polymer film on a topographically patterned
      substrate is an interesting approach for aligning isotropic dewetted structures.
      In this article, we investigate the influence of substrate feature height (H(S))
      on the dewetting pathway and final pattern morphology by studying the dewetting
      of polystyrene (PS) thin films on grating substrates with identical periodicity
      (lambda(P) = 1.5 MUm), but H(S) varying between 10 nm and 120 nm. We identify
      four distinct categories of final dewetted morphology, with different extent of
      ordering: (1) array of aligned droplets (H(S) ~ 120 nm); (2) aligned undulating
      ribbons (H(S) ~ 70-100 nm); (3) multilength scale structures with coexisting
      large droplets uncorrelated to the substrate and smaller droplets/ribbons aligned
      along the stripes (H(S) ~ 40-60 nm); and (4) large droplets completely
      uncorrelated to the substrate (H(S) < 25 nm). The distinct morphologies across
      the categories are attributed to two major factors: (a) whether the as-cast film
      is continuous (H(S)<= 80 nm) or discontinuous (H(S)>= 100 nm) and (b) in case of
      a continuous film, whether the film ruptures along each substrate stripe (H(S)>=
      70 nm) or with nucleation of random holes that are not correlated to the
      substrate features (H(S)<= 60 nm). While the ranges of H(S) values indicated in
      the parentheses are valid for PS films with an equivalent thickness (h(E)) ~ 50.3
      nm on a flat substrate, a change in h(E) merely alters the cut-off values of
      H(S), as the final dewetted morphologies and transition across categories remain
      generically unaltered. We finally show that the structures obtained by dewetting
      on different H(S) substrates exhibits different levels of hydrophobicity because
      of combined spatial variation of chemical and topographic contrast along the
      surface. Thus, the work reported in this article can find potential application
      in fabricating surfaces with controlled wettability.

PMID- 22999160
TI  - Detection of murine post-pneumonectomy lung regeneration by 18FDG PET imaging.
AB  - BACKGROUND: An intriguing biologic process in most adult mammals is post
      pneumonectomy lung regeneration, that is, the removal of one lung (pneumonectomy)
      results in the rapid compensatory growth of the remaining lung. The spatial
      dependence and metabolic activity of the rodent lung during compensatory lung
      regeneration is largely unknown. METHODS: To determine if murine lung
      regeneration could be detected in vivo, we studied inbred mice 3, 7, 14, and 21
      days after left pneumonectomy. The remaining lung was imaged using microCT as
      well as the glucose tracer 2-deoxy-2-[18 F]fluoro-d-glucose (18FDG) and positron
      emission tomography (PET). Because of the compliance of the murine chest wall,
      reproducible imaging required orotracheal intubation and pressure-controlled
      ventilation during scanning. RESULTS: After left pneumonectomy, the right lung
      progressively enlarged over the first 3 weeks. The cardiac lobe demonstrated the
      greatest percentage increase in size. Dry weights of the individual lobes largely
      mirrored the increase in lung volume. PET/CT imaging was used to identify
      enhanced metabolic activity within the individual lobes. In the cardiac lobe,
      18FDG uptake was significantly increased in the day 14 cardiac lobe relative to
      preoperative values (p < .05). In contrast, the 18FDG uptake in the other three
      lobes was not statistically significant at any time point. CONCLUSIONS: We
      conclude that the cardiac lobe is the dominant contributor to compensatory growth
      after murine pneumonectomy. Further, PET/CT scanning can detect both the
      volumetric increase and the metabolic changes associated with the regenerative
      growth in the murine cardiac lobe.

PMID- 22999161
TI  - Catecholamine production is differently regulated in splenic T- and B-cells
      following stress exposure.
AB  - OBJECTIVES: Stress is accompanied also by a rise in splenic catecholamines (CAs).
      However, indications about endogenous CA production in the spleen exist but there
      are no data about the cellular source of this production and possible
      modification by stress. Therefore, our aim was to investigate whether splenic T-
      and B-cells are one of main sources in the spleen expressing tyrosine hydroxylase
      (TH), enzyme crucial for CA biosynthesis, and phenylethanolamine N
      methyltransferase (PNMT) which is necessary for epinephrine production. We also
      investigated whether stress is able to modify expression of both enzymes and CA
      levels within these cell fractions as well as tried to explain functional
      consequences of changes observed. RESULTS: T-cells contain higher levels of TH
      mRNA than B-cells although protein levels appeared similar. On contrary, the PNMT
      mRNA and protein were higher in B-cells, which appeared to be the main source of
      PNMT in the spleen. T-cells increased TH and PNMT expression after acute stress
      while similar rise was observed in B-cells after repeated stress, most probably
      as a consequence of higher CA turnover in both cell populations. The rise in TH
      and PNMT was accompanied by an elevation of Bax/Bcl-2 mRNA ratio, number of
      apoptotic cells and also by a decline of IFN-gamma mRNA in both cell types.
      Reduction of IL-2 and IL-4 mRNA was also observed in B-cells. CONCLUSION: Stress
      induced stimulation of endogenous CA biosynthesis in lymphocytes is dependent on
      the type of lymphocyte population and duration of stressor and leads to
      attenuated IFN-gamma expression and induction of apoptosis. These changes might
      contribute to dysregulation of specific immune functions involving T- and B-cells
      and may decrease the ability to cope with intracellular agents following stress
      situations.

PMID- 22999162
TI  - Parasitic infections and immune function: effect of helminth infections in a
      malaria endemic area.
AB  - According to the hygiene hypothesis, reduced exposure to infections could explain
      the rise of atopic diseases in high-income countries. Helminths are hypothesised
      to alter the host's immune response in order to avoid elimination and, as a
      consequence, also reduce the host responsiveness to potential allergens. To
      elucidate the effect of current helminth infections on immune responsiveness in
      humans, we measured cytokine production in a rural Ghanaian population in an area
      with multiple endemic parasites including malaria, intestinal helminths and
      protozoa. Multiplex real-time PCR in stool samples was used for the detection of
      four gastrointestinal helminths, of which only Necator americanus was commonly
      present. A similar assay was used to test for Giardia lamblia in stool samples
      and malaria infection in venous blood samples. Levels of the cytokines
      interleukin (IL)-10, tumour necrosis factor (TNF)-alpha, IL-17, IL-6, IL-13, and
      interferon (IFN)-gamma were determined in whole-blood samples ex vivo-stimulated
      either with lipopolysaccharide (LPS) and zymosan (for innate cytokine production)
      or the T-cell mitogen phytohaemagglutinin (PHA). There were no significant
      differences in either innate or PHA-stimulated cytokine production dependent on
      current N. americanus infection. Plasmodium falciparum malarial infection was
      associated with a pro-inflammatory response indicated by increased innate
      production of TNF-alpha, IL-17 and IL-6. There was no clear pattern in cytokine
      responses dependent on G. lamblia-infection. In conclusion, in this rural
      Ghanaian population current N. americanus infections are not associated with
      altered immune function, while infection with P. falciparum is associated with
      pro-inflammatory innate immune responses.

PMID- 22999163
TI  - The antibacterial activity of some sulfonamides and sulfonyl hydrazones, and 2D
      QSAR study of a series of sulfonyl hydrazones.
AB  - Benzenesulfonicacid-1-methylhydrazide (1) and its four aromatic sulfonyl
      hydrazone derivatives (1a-1d), N-(3-amino-2-hydroxypropyl)benzene sulfonamide (2)
      and N-(2-hydroxyethyl)benzenesulfonamide (3) were synthesized and their
      structures were determined by IR, (1)H NMR, (13)C NMR, and LCMS techniques.
      Antibacterial activities of new synthesized compounds were evaluated against
      various bacteria strains by microdilution and disk diffusion methods. The
      experimental results show that presence of OH group on sulfonamides reduces the
      antimicrobial activity, and antimicrobial activities of the sulfonyl hydrazones
      (1a-1d) are smaller than that of the parent sulfonamide (1), except Candida
      albicans. In addition, 2D-QSAR analysis was performed on 28 aromatic sulfonyl
      hydrazones as antimicrobial agents against Escherichia coli and Staphylococcus
      aureus. In the QSAR models, the most important descriptor is total point-charge
      component of the molecular dipole for E. coli, and partial negative surface area
      (PNSA-1) for S. aureus.

PMID- 22999164
TI  - Structural, antimicrobial and computational characterization of 1-benzoyl-3-(5
      chloro-2-hydroxyphenyl)thiourea.
AB  - A new thiourea derivative, 1-benzoyl-3-(5-chloro-2-hydroxyphenyl)thiourea (bcht)
      has been synthesized from the reaction of 2-amino-4-chlorophenol with benzoyl
      isothiocyanate. The title compound has been characterized by elemental analyses,
      FT-IR, (13)C, (1)H NMR spectroscopy and the single crystal X-ray diffraction
      analysis. The structure of bcht derived from X-ray diffraction of a single
      crystal has been presented. The structural and spectroscopic data of the molecule
      in the ground state were calculated by using density functional method using 6
      311++G(d,p) basis set. The complete assignments of all vibrational modes were
      performed on the basis of the total energy distributions (TED). Isotropic
      chemical shifts ((13)C NMR and (1)H NMR) were calculated using the gauge
      invariant atomic orbital (GIAO) method. Theoretical calculations of bond
      parameters, harmonic vibration frequencies and nuclear magnetic resonance are in
      good agreement with experimental results. The UV absorption spectra of the
      compound that dissolved in ACN and MeOH were recorded. Bcht was also screened for
      antimicrobial activity against pathogenic bacteria and fungi.

PMID- 22999165
TI  - Management of hyperglycemia, dyslipidemia, and albuminuria in patients with
      diabetes and CKD: a systematic review for a KDOQI clinical practice guideline.
AB  - BACKGROUND: In 2007, the National Kidney Foundation (NKF) published clinical
      practice guidelines and recommendations for treating patients with diabetes and
      kidney diseases. Given recent studies that may enhance our understanding of the
      benefits and harms of glycemic, lipid, and albuminuria management in patients
      with diabetes and chronic kidney disease (CKD), the NKF commissioned a systematic
      review to evaluate data on the management of these patients. STUDY DESIGN:
      Systematic review and evidence synthesis. SETTING & POPULATION: Patients with
      type 1 or 2 diabetes with or without CKD. SELECTION CRITERIA FOR STUDIES: English
      language publications indexed in the MEDLINE database from January 2003 to
      October 2010, as well as cited references in these publications and publications
      identified after consultation with the NKF Diabetes Work Group were screened.
      Randomized controlled trials providing evidence for the management of
      hyperglycemia, dyslipidemia, and albuminuria in individuals with diabetes were
      included. INTERVENTIONS: (1) Intensive glycemic control; (2) lipid management;
      (3) interventions aimed at prevention of incident albuminuria and/or progression
      of albuminuria in normotensive patients. OUTCOMES: For all interventions, all
      cause mortality was the primary outcome and secondary clinical outcomes included
      death from cardiovascular causes, incident kidney failure, and nonfatal
      cardiovascular events. Intermediate outcomes included changes in albuminuria and
      measures of kidney function. For intensive glycemic control only, severe and mild
      hypoglycemia were secondary and intermediate outcomes, respectively. RESULTS: 5
      studies (n=27,159) assessed the impact of intensive versus conventional glycemic
      control strategies on clinical outcomes in type 2 diabetes. Intensive glycemic
      control reduced the development of micro- and macroalbuminuria, but did not
      reduce the incidence of primary or secondary clinical outcomes and was associated
      with a 2.5-fold increase in severe hypoglycemia. 11 studies (n=7,539) assessed
      lipid management. Statins did not reduce all-cause mortality or stroke compared
      to placebo in adults with diabetes and CKD. Fenofibrate increased regression of
      microalbuminuria to normoalbuminuria compared to placebo. 3 studies reported
      inconsistent effects of different angiotensin II receptor blockers on the
      incidence of microalbuminuria, and one study reported that telmisartan reduced
      macroalbuminuria in normotensive participants. No study demonstrated a benefit on
      primary or secondary clinical outcomes. LIMITATIONS: Patients with CKD
      constituted a subgroup in most studies. Substantial heterogeneity with respect to
      population, interventions, outcome measures, and duration of follow-up.
      CONCLUSIONS: Intensive glycemic control and lipid interventions did not improve
      clinical outcomes in patients with type 2 diabetes. Although interventions
      typically improved albuminuria, evidence was insufficient to determine whether
      treatment of albuminuria in normotensive patients provides beneficial effects on
      clinical outcomes. More intensive clinical management of patients with diabetes
      and CKD has inherent risks, including severe hypoglycemia, which should be
      considered when formulating treatment strategies.

PMID- 22999166
TI  - Pursuing permanent hemodialysis vascular access in patients with a poor
      prognosis: juxtaposing potential benefit and harm.
AB  - For patients with end-stage renal disease requiring hemodialysis, the native
      arteriovenous fistula remains the gold standard of vascular access, with tunneled
      cuffed central venous catheters reserved for temporary use or as a last resort in
      patients for whom a permanent vascular access is not possible. It is expected
      that most patients receiving hemodialysis will be suitable for arteriovenous
      fistula placement, with suitable patients defined as those: (1) for whom long
      term dialysis is expected to confer benefit, (2) with vascular anatomy amenable
      to arteriovenous fistula placement, and (3) with progressive irreversible kidney
      failure who are more likely to require dialysis than to die before reaching
      dialysis dependence. The present article reviews considerations for vascular
      access decision making, focusing on older patients and those with a poor
      prognosis, weighing the risks and benefits of arteriovenous fistulas,
      arteriovenous grafts, and central venous catheters and emphasizing that in the
      process of vascular access decision making for such patients, medical and ethical
      obligations to avoid central venous catheters must be balanced by the obligation
      to do no harm.

PMID- 22999167
TI  - Steady-state kinetic characterization of sesquiterpene synthases by gas
      chromatography-mass spectroscopy.
AB  - Sesquiterpene synthases produce a wide variety of structurally diverse
      hydrocarbon products from a single substrate: farnesyl pyrophosphate. Each enzyme
      will often produce a multitude of products for which the kinetic efficiency is
      traditionally measured using a radioactivity assay. Here, we introduce a gas
      chromatography-mass spectroscopy-based assay to measure the formation of a single
      abundant product from which the kinetic parameters of the enzyme in question can
      be elucidated. We present an accounting of experimental components and
      considerations, such as solution conditions and instrument parameters, necessary
      to perform a standardized vial assay experiment. Further, we outline pilot
      experiments to establish analyte quantification and the linear range of enzyme
      concentration versus reaction velocity. Finally, we describe a protocol for a
      steady-state kinetics experiment, and the processing of experimental data to
      produce a Michaelis-Menten plot enabling one to derive kinetic parameters.

PMID- 22999168
TI  - Automating gene library synthesis by structure-based combinatorial protein
      engineering: examples from plant sesquiterpene synthases.
AB  - Structure-based combinatorial protein engineering (SCOPE) is a homology
      independent recombination method to create multiple crossover gene libraries by
      assembling defined combinations of structural elements ranging from single
      mutations to domains of protein structure. SCOPE was originally inspired by DNA
      shuffling, which mimics recombination during meiosis, where mutations from
      parental genes are "shuffled" to create novel combinations in the resulting
      progeny. DNA shuffling utilizes sequence identity between parental genes to
      mediate template-switching events (the annealing and extension of one parental
      gene fragment on another) in PCR reassembly reactions to generate crossovers and
      hence recombination between parental genes. In light of the conservation of
      protein structure and degeneracy of sequence, SCOPE was developed to enable the
      "shuffling" of distantly related genes with no requirement for sequence identity.
      The central principle involves the use of oligonucleotides to encode for
      crossover regions to choreograph template-switching events during PCR assembly of
      gene fragments to create chimeric genes. This approach was initially developed to
      create libraries of hybrid DNA polymerases from distantly related parents, and
      later developed to create a combinatorial mutant library of sesquiterpene
      synthases to explore the catalytic landscapes underlying the functional
      divergence of related enzymes. This chapter presents a simplified protocol of
      SCOPE that can be integrated with different mutagenesis techniques and is
      suitable for automation by liquid-handling robots. Two examples are presented to
      illustrate the application of SCOPE to create gene libraries using plant
      sesquiterpene synthases as the model system. In the first example, we outline how
      to create an active-site library as a series of complex mixtures of diverse
      mutants. In the second example, we outline how to create a focused library as an
      array of individual clones to distil minimal combinations of functionally
      important mutations. Through these examples, the principles of the technique are
      illustrated and the suitability of automating various aspects of the procedure
      for given applications are discussed.

PMID- 22999169
TI  - In planta transient expression analysis of monoterpene synthases.
AB  - In vitro-based analyses of monoterpene synthase (mono-TPS) enzymes have led to a
      wealth of knowledge regarding their catalytic behavior, the mechanistic
      principles governing their product specificity, and the molecular basis for their
      evolution. However, the efficient production of active enzymes in Escherichia
      coli or yeast can be challenging. Agrobacterium-mediated transient expression in
      tobacco leaves is increasingly being used as a viable alternative to in vitro
      based approaches for the production and functional analysis of a wide range of
      plant proteins. Transient expression is well suited for qualitative and
      semiquantitative analyses of mono-TPS enzyme product specificity and, in
      conjunction with standard volatile analysis techniques, provides an efficient
      tool for screening mono-TPS function in planta. The primary advantages of this
      system for mono-TPS analysis are that both mono-TPS genomic clones and cDNAs can
      be cloned directly into plant expression vectors without modification and
      expressed enzymes can be analyzed without the need for purification or endogenous
      precursor addition. Here, we describe a simple and cost-effective method for the
      in planta functional analysis of plant mono-TPS enzymes. This method can
      accommodate both the analysis of single genes and the scaling for more high
      throughput functional screening of mono-TPS gene families or mutant libraries.

PMID- 22999170
TI  - Natural rubber biosynthesis in plants: rubber transferase.
AB  - Rubber biosynthesis in plants is a fascinating biochemical system, which evolved
      at the dawn of the dicotyledoneae and is present in at least four of the
      dictolydonous superorders. Rubber biosynthesis is catalyzed by a membrane complex
      in a monolayer membrane envelope, requires two distinct substrates and a divalent
      cation cofactor, and produces a high-molecular-weight isoprenoid polymer. A solid
      understanding of this system underpins valuable papers in the literature.
      However, the published literature is rife with unreliable reports in which the
      investigators have fallen into traps created by the current incomplete
      understanding of the biochemistry of rubber synthesis. In this chapter, we
      attempt to guide both new and more established researchers around these pitfalls.

PMID- 22999171
TI  - Discovery and characterization of terpenoid biosynthetic pathways of fungi.
AB  - Fungi produce a myriad of terpenoids with a broad range of biological activities,
      many of which can be adapted to human use. This requires knowledge of the enzymes
      responsible for the biosynthesis of these compounds. Herein, we describe
      strategies for identification and characterization of putative biosynthetic
      genes, structural examination of important pathway enzymes with a focus on
      altering activity, and identification of biosynthetic clusters, and genome mining
      for yet-to-be-discovered pathways. Fungi are a particularly attractive class of
      organism for terpenoid pathway discovery, as they often cluster their
      biosynthetic genes. The affordability of genome sequencing and the relatively
      small size of fungal genomes further simplify this process. While only a select
      few fungal strains are genetically tractable, many terpenoid biosynthetic genes
      are functional in Escherichia coli and Saccharomyces cerevisiae, allowing easy
      characterization. Identification of new terpenoid biosynthetic pathways has the
      potential to uncover new pharmaceutical compounds and establish new strategies
      for metabolic engineering.

PMID- 22999172
TI  - Menaquinone biosyntheses in microorganisms.
AB  - In prokaryotes, menaquinone (MK) is involved in an electron-transfer pathway. Its
      biosynthesis was established in the 1970s and 1980s with Escherichia coli.
      However, a bioinformatic analysis of whole genome sequences has suggested the
      presence of an alternative pathway. We investigated a novel pathway in a
      Streptomyces strain. The (13)C-labeling pattern of MK purified from a
      Streptomyces strain grown on [U-(13)C]glucose was quite different from that of E.
      coli. We searched for candidate genes participating in the pathway by in silico
      screening, and the involvement of these genes in the pathway was confirmed by
      gene-disruption experiments. We also employed mutagenesis to isolate auxotrophic
      mutants and used these mutants as hosts for shotgun cloning experiments.
      Metabolites that accumulated in the culture broth of the mutants were isolated
      and their structures were determined. Taken together, the results indicated an
      alternative pathway (futalosine (FL) pathway). Moreover, there were three
      possible routes in the early part of the FL pathway. FL was directly formed by
      MqnA in Thermus thermophilus and converted into dehypoxanthinyl FL (DHFL). In
      Acidothermus cellulolyticus, Streptomyces coelicolor, and Helicobacter pylori,
      aminodeoxyfutalosine (AFL) was formed by MqnA. In the case of the former two
      strains, AFL was converted to FL by deaminases then to DHFL. In contrast, AFL was
      directly converted to DHFL in H. pylori.

PMID- 22999173
TI  - Diversity and analysis of bacterial terpene synthases.
AB  - Terpenoid compounds are generally considered to be plant or fungal metabolites,
      although a small number of odorous terpenoid metabolites of bacterial origin have
      been known for many years. Recently, extensive bacterial genome sequencing and
      bioinformatic analysis of deduced bacterial proteins using a profile hidden
      Markov model have revealed more than a hundred distinct predicted terpene
      synthase genes. Although some of these synthase genes might be silent in the
      parent microorganisms under normal laboratory culture conditions, the controlled
      overexpression of these genes in a versatile heterologous host has made it
      possible to identify the biochemical function of cryptic genes and isolate new
      terpenoid metabolites.

PMID- 22999174
TI  - Platensimycin and platencin biosynthesis in Streptomyces platensis, showcasing
      discovery and characterization of novel bacterial diterpene synthases.
AB  - Diterpenoid natural products cover a vast chemical diversity and include many
      medicinally and industrially relevant compounds. All diterpenoids derive from a
      common substrate, (E,E,E)-geranylgeranyl diphosphate, which is cyclized into one
      of many scaffolds by a diterpene synthase (DTS). While diterpene biosynthesis has
      been extensively studied in plants and fungi, bacteria are now recognized for
      their production of unique diterpenoids and are likely to harbor an underexplored
      reservoir of new DTSs. Bacterial diterpenoid biosynthesis can be exploited for
      the discovery of new natural products, a better mechanistic understanding of
      DTSs, and the rational engineering of whole metabolic pathways. This chapter
      describes methods and protocols for identification and characterization of
      bacterial DTSs, based on our recent work with the DTSs involved in platensimycin
      and platencin biosynthesis.

PMID- 22999175
TI  - Strategies for engineering plant natural products: the iridoid-derived
      monoterpene indole alkaloids of Catharanthus roseus.
AB  - The manipulation of pathways to make unnatural variants of natural compounds, a
      process often termed combinatorial biosynthesis, has been robustly successful in
      prokaryotic systems. The development of approaches to generate new-to-nature
      compounds from plant-based pathways is, in comparison, much less advanced.
      Success will depend on the specific chemistry of the pathway, as well as on the
      suitability of the plant system for transformation and genetic manipulation. As
      plant pathways are elucidated, and can be heterologously expressed in hosts that
      are more amenable to genetic manipulation, biosynthetic production of new-to
      nature compounds from plant pathways will become more widespread. In this
      chapter, some of the key strategies that have been developed for metabolic
      engineering of plant pathways, namely directed biosynthesis, mutasynthesis, and
      pathway incorporation of engineered enzymes are highlighted. The iridoid-derived
      monoterpene indole alkaloids from C. roseus, which are the focus of this chapter,
      provide an excellent system for developing these strategies.

PMID- 22999176
TI  - Discovery and functional analysis of monoterpenoid indole alkaloid pathways in
      plants.
AB  - Numerous difficulties have been associated with forward genetic approaches to
      identify, and functionally characterize genes involved in the biosynthesis,
      regulation, and transport of monoterpenoid indole alkaloids (MIAs). While the
      identification of certain classes of genes associated with MIA pathways has
      facilitated the use of homology-based approaches to clone other genes catalyzing
      similar reactions in other parts of the pathway, this has not greatly speeded up
      the pace of gene discovery for the diversity of reactions involved. Compounding
      this problem has been the lack of knowledge or even availability of certain MIA
      intermediates that would be required to establish a novel enzyme reaction to
      functionally identify a biosynthetic step or the candidate gene product involved.
      The advent of inexpensive sequencing technologies for transcriptome and genome
      sequencing, combined with proteomics and metabolomics, is now revolutionizing the
      pace of gene discovery associated with MIA pathways and their regulation. The
      discovery process uses large databases of genes, proteins, and metabolites from
      an ever-expanding list of nonmodel plant species competent to produce and
      accumulate MIAs. Comparative bioinformatics between species, together with gene
      expression analysis of particular tissue, cell, and developmental types, is
      helping to identify target genes that can then be investigated for their possible
      role in an MIA pathway by virus-induced gene silencing. Successful silencing not
      only confirms the involvement of the candidate gene but also allows
      identification of the pathway intermediate involved. In many circumstances, the
      pathway intermediate can be isolated for use as a substrate in order to confirm
      gene function in heterologous bacterial, yeast, or plant expression systems.

PMID- 22999177
TI  - Biochemical genomics for gene discovery in benzylisoquinoline alkaloid
      biosynthesis in opium poppy and related species.
AB  - Benzylisoquinoline alkaloids (BIAs) are a large, diverse group of ~2500
      specialized plant metabolites. Many BIAs display potent pharmacological
      activities, including the narcotic analgesics codeine and morphine, the
      vasodilator papaverine, the cough suppressant and potential anticancer drug
      noscapine, the antimicrobial agents sanguinarine and berberine, and the muscle
      relaxant (+)-tubocurarine. Opium poppy remains the sole commercial source for
      codeine, morphine, and a variety of semisynthetic drugs, including oxycodone and
      buprenorphine, derived primarily from the biosynthetic pathway intermediate
      thebaine. Recent advances in transcriptomics, proteomics, and metabolomics have
      created unprecedented opportunities for isolating and characterizing novel BIA
      biosynthetic genes. Here, we describe the application of next-generation
      sequencing and cDNA microarrays for selecting gene candidates based on
      comparative transcriptome analysis. We outline the basic mass spectrometric
      techniques to perform deep proteome and targeted metabolite analyses on BIA
      producing plant tissues and provide methodologies for functionally characterizing
      biosynthetic gene candidates through in vitro enzyme assays and transient gene
      silencing in planta.

PMID- 22999178
TI  - Analysis and modification of ergot alkaloid profiles in fungi.
AB  - The ergot alkaloids are a family of secondary metabolites produced by a
      phylogenetically discontinuous group of fungi. Various members of the family are
      important in agriculture, where they accumulate in grain crops or forage grasses
      and adversely affect humans or animals who consume them. Other ergot alkaloids
      have been used clinically to treat a variety of diseases. Because of their
      significance in agriculture and medicine, the ability to detect and quantify
      these alkaloids from a variety of substrates is important. The primary analytical
      approach for these purposes has been high performance liquid chromatography. The
      ability to manipulate ergot alkaloid production in fungi, by transformation
      mediated approaches, has been useful for studies on the biosynthesis of these
      alkaloids and may have practical application in agriculture and medicine. Such
      modifications have been informed by comparative genomic approaches, which have
      provided information on the gene clusters associated with ergot alkaloid
      biosynthesis.

PMID- 22999179
TI  - Engineering of glucosinolate biosynthesis: candidate gene identification and
      validation.
AB  - The diverse biological roles of glucosinolates as plant defense metabolites and
      anticancer compounds have spurred a strong interest in their biosynthetic
      pathways. Since the completion of the Arabidopsis genome, functional genomics
      approaches have enabled significant progress on the elucidation of glucosinolate
      biosynthesis, although in planta validation of candidate gene function often is
      hampered by time-consuming generation of knockout and overexpression lines in
      Arabidopsis. To better exploit the increasing amount of data available from
      genomic sequencing, microarray database and RNAseq, time-efficient methods for
      identification and validation of candidate genes are needed. This chapter covers
      the methodology we are using for gene discovery in glucosinolate engineering,
      namely, guilt-by-association-based in silico methods and fast proof-of-function
      screens by transient expression in Nicotiana benthamiana. Moreover, the lessons
      learned in the rapid, transient tobacco system are readily translated to our
      robust, versatile yeast expression platform, where additional genes critical for
      large-scale microbial production of glucosinolates can be identified. We
      anticipate that the methodology presented here will be beneficial to elucidate
      and engineer other plant biosynthetic pathways.

PMID- 22999180
TI  - Structure-function analyses of plant type III polyketide synthases.
AB  - Plant type III polyketide synthases (PKSs) form a superfamily of biosynthetic
      enzymes involved in the production of a plethora of polyketide-derived natural
      products important for ecological adaptations and the fitness of land plants.
      Moreover, tremendous interest in bioengineering of type III PKSs to produce high
      value compounds is increasing. Compared to type I and type II PKSs, which form
      either large modular protein complexes or dissociable molecular assemblies, type
      III PKSs exist as smaller homodimeric proteins, technically more amenable for
      detailed quantitative biochemical and phylogenetic analyses. In this chapter, we
      summarize a collection of approaches, including bioinformatics, genetics, protein
      crystallography, in vitro biochemistry, and mutagenesis, together affording a
      comprehensive interrogation of the structure-function-evolutionary relationships
      in the plant type III PKS family.

PMID- 22999181
TI  - Engineering of plant type III polyketide synthases.
AB  - Members of the chalcone synthase superfamily of type III polyketide synthases
      (PKSs) catalyze iterative condensations of CoA thioesters to produce a variety of
      polyketide scaffolds with remarkable structural diversity and biological
      activities. The homodimeric type III PKSs share a common three-dimensional
      overall fold with a conserved Cys-His-Asn catalytic triad; notably, only a slight
      modification of the active site dramatically expands the catalytic repertoire of
      the enzymes. In addition, the enzymes exhibit extremely promiscuous substrate
      specificities, and accept a variety of nonphysiological substrates, making the
      type III PKSs an excellent platform for the further production of unnatural,
      novel polyketide scaffolds with promising biological activities. This chapter
      summarizes recent advances in the engineering of plant type III PKS enzymes in
      our laboratories, using approaches combining structure-based enzyme engineering
      and precursor-directed biosynthesis with rationally designed substrate analogs.

PMID- 22999182
TI  - Type III polyketide synthases in microorganisms.
AB  - Type III polyketide synthases (PKSs) are simple homodimers of ketosynthases which
      catalyze the condensation of one to several molecules of extender substrate onto
      a starter substrate through iterative decarboxylative Claisen condensation
      reactions. Type III PKSs have been found in bacteria and fungi, as well as
      plants. Microbial type III PKSs, which are involved in the biosynthesis of some
      lipidic compounds and various secondary metabolites, have several interesting
      characteristics that are not shared by plant type III PKSs. Further, many
      compounds produced by microbial type III PKSs have significant biological
      functions and/or important pharmaceutical activities. Thus, studies on this class
      of enzymes will expand our knowledge of the biosynthetic machineries that
      generate natural products and generate new findings about microbial physiology.
      The recent development of next-generation DNA sequencing has allowed for an
      increase in the number of microbial genomes sequenced and the discovery of many
      microbial type III PKS genes. Here, we describe basic methods to study microbial
      type III PKSs whose genes are easy to clone.

PMID- 22999183
TI  - Natural product biosynthesis by microorganisms and plants, Part A. Preface.

PMID- 22999184
TI  - Size-selected growth of transparent well-aligned ZnO nanowire arrays.
AB  - This paper reports the effect of precursor concentration, growth temperature,
      and growth time on the size and density of ZnO nanowire arrays (ZNAs). The well
      aligned ZNAs were grown on indium tin oxide substrate using a facile chemical
      bath deposition method. The results showed that the ZnO nanowires could be
      tailored to the desired sizes with a simple variation of the growth parameters.
      Optical transmission spectra revealed a sufficient transparency of the ZNAs,
      qualifying them for photovoltaic and other optoelectronic applications. An
      inverted hybrid solar cell was fabricated using the ZNAs as the electron
      collecting layer, and the solar cell exhibited a power conversion efficiency of
      0.91%.

PMID- 22999185
TI  - Military trauma care in Birmingham: observational study of care requirements and
      resource utilisation.
AB  - BACKGROUND: The Royal Centre for Defence Medicine is located at University
      Hospitals Birmingham (UHB). Since 2001 all UK military casualties injured on
      active duty have been repatriated here for their initial treatment. This service
      evaluation was performed to quantify the work undertaken, with the aim of
      providing a snapshot of a year's military trauma work in order to inform the
      delivery of trauma care in both the military and civilian setting. METHODS:
      Military patients admitted with traumatic injuries over a 12-month period were
      identified and the hospital notes and electronic records reviewed. Data were
      collected focusing on three areas - the details of the injury, information about
      the in-patient admission, and surgical interventions performed. RESULTS: A total
      of 388 patients were used in the analysis. Median total length of stay was 10.5
      days (IQR: 4-26, range: 0-137 days), and a median 6.0 days (IQR: 3.0-11.0, range:
      1-49 days) was spent on intensive care by 125 patients. Surgical intervention was
      required for 278 (71.6%) patients, with a median of 2.0 operations (IQR: 1.0-4.0,
      range: 1-27) or 170 min (IQR: 90.0-570.0, range 20-4735 min) operating time per
      patient. 77% of these patients had their first procedure within 24h of arrival.
      Improvised explosives accounted for 50.5% of injuries seen. Spearman rank
      correlation between New Injury Severity Score with length of stay demonstrated
      significant correlation (p<0.001), with a coefficient of 0.640. A model
      predicting length of stay based on New Injury Severity Score was devised for
      patients with battle injuries. CONCLUSION: This report of 12 months work at UHB
      demonstrates the service commitment to these casualties, describing the burden of
      care and resource requirements for military trauma patients.

PMID- 22999186
TI  - Ultrasound: easy and reliable technique in diagnosis of occult traumatic
      pneumothorax.

PMID- 22999187
TI  - Immune response during interferon beta-1b treatment in patients with multiple
      sclerosis who experienced relapses and those who were relapse-free in the START
      study.
AB  - We measured immune markers in subjects with multiple sclerosis (MS) treated with
      IFNbeta-1b for 12 months. IL-17 levels were significantly higher at Month 6
      (p=0.036) in relapsing subjects while BDNF levels were significantly higher at
      Month 3 (p=0.028) in relapse-free subjects. Change from baseline in IL-4 levels
      inversely correlated with disability score whereas change from baseline in IL
      10/IFN-gamma ratio inversely correlated with occurrence of relapses. CXCR3+CD8+ T
      cells tended to be higher but declined with treatment in relapse-free compared
      with relapsing subjects. Findings show the potential of cytokine and neurotrophic
      factors as biomarkers of clinical response to IFNbeta-1b.

PMID- 22999188
TI  - Antibodies against Wnt receptor of muscle-specific tyrosine kinase in myasthenia
      gravis.
AB  - Muscle-specific tyrosine kinase (MuSK) antibodies are detected in a proportion of
      myasthenia gravis (MG) patients who are negative for acetylcholine receptor
      (AChR) antibodies and have prominent bulbar weakness and crises. In the MuSK
      ectodomains, the immunoglobulin-like 1 and 2 domains (Ig1/2) mediate the agrin
      Lrp4-MuSK signaling and the cysteine-rich domain (CRD) mediates the Wnt-MuSK
      Dishevelled signaling; both contribute to AChR clustering. Immunoblotting against
      recombinant proteins showed MuSK Ig1/2 antibodies in 33 anti-AChR-negative MG
      patients; 10 patients of them (30%) were additionally positive for MuSK CRD
      antibodies. The result suggests that MuSK antibodies have heterogeneity in their
      binding to functional domains of MuSK.

PMID- 22999189
TI  - Cellular cooperation: insights from microbes.
AB  - Cooperation between cells is a widespread phenomenon in nature, found across
      diverse systems ranging from microbial populations to multicellular organisms.
      For cooperation to evolve and be maintained within a population of cells, costs
      due to competition have to be outweighed by the benefits gained through
      cooperative actions. Because cooperation generally confers a cost to the
      cooperating cells, defector cells that do not cooperate but reap the benefits of
      cooperation can thrive and eventually drive the cooperating phenotypes to
      extinction. Here we summarize recent advances made in understanding how
      cooperation and multicellularity can evolve in microbial populations in the face
      of such conflicts and discuss parallels with cell populations within
      multicellular organisms.

PMID- 22999190
TI  - Breaking away: matrix remodeling from the leading edge.
AB  - Substantial progress has been made in recent years toward understanding the
      molecular mechanisms by which tumor cells, and the supporting stroma, degrade
      confining matrix during migration. Significant attention has been focused on
      understanding the biology of several dynamic and distinct, but remarkably
      related, cell structures that include lamellipodia, focal adhesions (FAs),
      filopodia, podosomes, and invadopodia. How these invasive organelles assemble and
      function is a topic of intense study. Most exciting has been the recent progress
      made by combining advanced microscope technologies with a wide variety of
      different 3D matrices, tissue explants, or even living model organisms. From
      these approaches, it has become increasingly evident that the conventional
      definitions of these invasive structures may be less clear than was previously
      thought.

PMID- 22999191
TI  - Feasibility of sonographer-administered echocontrast in a large-volume tertiary
      care echocardiography laboratory.
AB  - BACKGROUND: Contrast echocardiography has been shown to improve diagnostic
      quality, especially in technically difficult patients. However, the learning
      curve and increased time for preparation and image acquisition have led to low
      use. METHODS: We sought to determine whether the contrast echocardiography
      procedure performed independently by a specialized, trained sonographer could
      improve efficiency. In our centre, routine echocardiograms were scheduled for 1
      hour, and any study exceeding 1 hour would result in patient booking
      cancellations. We compared the standard of care, in which a physician or nurse
      administers echocontrast, with a sonographer-administered program (SAP). RESULTS:
      The time to complete contrast echocardiograms was significantly reduced by the
      SAP strategy (43 min 17 s +/- 23 min 42 s vs 1 h 1 min 6 s +/- 31 min 0 s, P <
      0.001). Subgroup analysis of the inpatients and outpatients demonstrated similar
      results. Only 10% of studies (6 of 61) in the SAP exceeded 60 minutes, compared
      with 45% (34 of 76) in the standard-of-care group (P < 0.001). Based on study
      volumes in our centre, the net improvement in productivity with the SAP could be
      up to 5.3% annually. CONCLUSION: Sonographer-administered echocontrast is
      feasible and potentially removes a barrier to implementation of contrast
      echocardiography.

PMID- 22999192
TI  - Monomorphic ventricular tachycardia 25 years post surgical ablation for Wolff
      Parkinson-White.
AB  - The first surgical ablation of an accessory pathway for the treatment of Wolff
      Parkinson-White (WPW) syndrome was performed in 1968, and surgery remained first
      line therapy until the advent of catheter ablation techniques in the early 1990s.
      Current indications for surgical ablation of WPW syndrome are limited to ablation
      failures. To this day, there has been no long-term follow-up of these surgically
      treated patients. We describe the case of a man, aged 54 years, who developed
      ventricular tachycardia 25 years after surgical ablation of WPW. This is first
      reported case of ventricular tachycardia following an epicardial surgical
      cryoablation technique for WPW.

PMID- 22999193
TI  - Genetic markers of inflammation and their role in cardiovascular disease.
AB  - Atherosclerosis and associated cardiovascular diseases (CVD) are multifaceted
      disorders, influenced by environmental and heritable risk factors. Inflammation
      plays a significant role in each stage of atherosclerosis and as such, discovery
      and characterization of inflammatory biomarkers associated with risk of CVD is an
      active area of research. Because of the strong predicted genetic components of
      both CVD and inflammatory biomarkers, there is interest in identifying genetic
      determinants of inflammatory markers and characterizing their role in CVD. Recent
      developments in the methodological approaches of genetic epidemiology, especially
      genome-wide association studies and Mendelian randomization studies, have been
      effective in identifying novel gene associations and determining the causality of
      these genes with CVD. In this review, we will summarize the current understanding
      of the genetic architecture of inflammatory markers. The markers selected for
      this review include C-reactive protein, soluble intercellular adhesion molecule
      1, interleukin-6, and P-selectin.

PMID- 22999194
TI  - Primary micro neuroendocrine tumor arising in a horseshoe kidney with cyst:
      report of a case and review of literature.
AB  - Neuroendocrine tumors are a heterogeneous group of neoplasms that arise from
      neuroendocrine cells. Primary renal neuroendocrine tumors are among the most
      unusual of all renal neoplasms, since neuroendocrine cells are not found within
      normal renal parenchyma. Here, a case of primary micro neuroendocrine tumor
      (about 4.7 mm*2 mm) arising in the horseshoe kidney with a cyst of a 45-year-old
      man was reported and a literature review was written. Virtual slides: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2121156944757267.

PMID- 22999195
TI  - Challenges in the development of bioanalytical liquid chromatography-mass
      spectrometry method with emphasis on fast analysis.
AB  - The development of bioanalytical methods has become more and more challenging
      over the past years due to very demanding requirements in terms of method
      reliability, sensitivity, speed of analysis and sample throughput. LC-MS/MS has
      established itself as a method of choice for routine analysis of biological
      materials. A development of such method consists of several steps including
      sample preparation and clean-up step, efficient chromatographic separation,
      sensitive and selective detection of analytes in complex matrices, a choice of
      convenient data processing and calibration approach and finally method
      validation. Each of these steps has its own constraints and challenges, which are
      discussed in detail in this review. Novel and modern approaches in sample
      preparation, chromatography and detection are especially emphasized. Attention is
      paid to proper calibration approach and matrix effects that can seriously affect
      method accuracy and precision.

PMID- 22999196
TI  - Novel amide polar-embedded reversed-phase column for the fast liquid
      chromatography-tandem mass spectrometry method to determine polyether ionophores
      in environmental waters.
AB  - A fast chromatographic method has been developed that takes less than 5 min per
      run to determine five polyether ionophores with a novel amide polar-embedded
      reversed-phase column coupled to a triple quadrupole mass spectrometer. A
      comparison between Oasis HLB and Oasis MAX sorbents for the solid-phase
      extraction was done. Oasis HLB sorbent gave recoveries close to 90% and the
      repeatability (%RSD, 25-100 ng/L, n=3) of the method was less than 7% for all
      compounds in all matrices. The presence of polyether ionophores in environmental
      waters such as river water and sewage was investigated. Monensin and narasin were
      frequently determined in influent and effluent sewage at concentrations from 10
      ng/L to 47 ng/L in influents and from 6 ng/L to 34 ng/L in effluents. In river
      waters, polyether ionophores were not detected in any sample.

PMID- 22999197
TI  - Enantioselective two-dimensional high-performance liquid chromatographic
      determination of N-methyl-D-aspartic acid and its analogues in mammals and
      bivalves.
AB  - A validated and fully automated chiral 2D-HPLC system was developed for the
      simultaneous determination of N-methyl-d-aspartic acid (NMDA) analogues by
      combining a long microbore-monolithic ODS column (0.53 mm i.d.* 1,000 mm) and
      narrowbore-enantioselective columns (1.5mm i.d.*150 or 250 mm). The target
      analytes, enantiomers of N-methylaspartic acid (NMA) and N-methylglutamic acid
      (NMG), were precolumn-derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD
      F) and detected by their fluorescence. The values of the lower limit of
      quantification for these enantiomers were 2.5 fmol. In the tissues and plasma of
      rats, neither NMA nor NMG were detected. On the other hand, in the mantle and
      foot of Scapharca broughtonii, a large amount of NMDA was present (170.1 and 43.5
      nmol/g), and the enantiomers of NMG were also observed. Meretrix lusoria
      contained NMDA (29.3 nmol/g) and NMLG (13.8 nmol/g), and Ruditapes philippinarum
      contained only NMLG (2.6 nmol/g). The obtained results were confirmed using three
      different enantioselective columns and also using a 2D-HPLC-MS/MS system. These
      results indicated that neuroactive d-amino acid, NMDA, and its analogues were
      present in animals, and their physiological significance is expected to be
      clarified.

PMID- 22999198
TI  - Pulsed electromembrane extraction: a new concept of electrically enhanced
      extraction.
AB  - In the present work, pulsed electromembrane extraction (PEME) is introduced for
      the first time as an efficient and inexpensive method for the extraction of
      ionizable compounds from different matrices. The setup proposed for
      electromembrane extraction (EME) provides a very stable system and satisfactory
      repeatability (RSDs<4.4) in comparison with existing methods. In this paper, PEME
      is conducted for the extraction of model analytes from biological fluids. The
      effective parameters such as extraction time, applied voltage and the duration of
      pulse and outage period are optimized using the experimental design.
      Preconcentration factors in the range of 100-140 and recoveries in the range of
      95-108 were obtained in different biological matrices. The linear dynamic ranges
      of 5-200 ng mL(-1) (with correlation coefficient higher than 0.9955) and limits
      of detection of 1.0 ng mL(-1) were obtained for both of the drugs. The figures of
      merit of PEME were compared with the results from conventional EME, which proves
      the advantages of the proposed technique.

PMID- 22999199
TI  - Automated preconcentration and analysis of organic compounds by on-line hollow
      fiber liquid-phase microextraction-high performance liquid chromatography.
AB  - The present work describes the first automated instrument, based on on-line
      hollow fiber liquid-phase microextraction (HF-LPME)-high performance liquid
      chromatography (HPLC), for the preconcentration and determination of organic
      compounds in various matrices. Using an automated syringe pump for loading the
      supported liquid membrane and acceptor solvents, a platform lift for moving the
      sample vial, a sampling loop for on-line injection of the extract to HPLC, along
      with an electronic board with an AVR microcontroller for storage of data and
      instrument programs, a sample preparation-HPLC method was developed that allowed
      sample extraction and extract injection to be carried out completely
      automatically. Pyridine and pyridine derivatives were chosen for the development
      and for testing the applicability of the automated instrument. The limits of
      detection (3 times the S/N) ranged from 0.5 to 1.0 MUgL(-1). Effective
      preconcentration of the analytes was also achieved (preconcentration factors of
      between 40 and 220). The main advantages of the method developed are minimum
      sample manipulation, full automation, suitable extraction time, low solvent
      consumption, and ease of use. The applicability of the on-line automated HF
      LPME/HPLC-UV instrument was validated for quantitative extraction and
      determination of pyridines in cigarette smoke.

PMID- 22999200
TI  - Simultaneous determination of five pyrazole fungicides in cereals, vegetables and
      fruits using liquid chromatography/tandem mass spectrometry.
AB  - The sensitive analytical method using quick, easy, cheap, effective, rugged, and
      safe (QuEChERS) procedure for simultaneous determination of five novel pyrazole
      fungicides residues in cereals (rice and wheat), vegetables (cucumber, tomato,
      and lettuce), and fruits (apple and grape) was developed by liquid chromatography
      coupled with tandem mass spectrometry (LC-MS/MS). The five pyrazole fungicides
      (bixafen, fluxapyroxad, furametpyr, pyraclostrobin, and rabenzazole) were
      extracted from seven matrices using acetonitrile and subsequently cleaned up by
      octadecylsilane (C(18)) or graphitized carbon black (GCB) prior to LC-MS/MS
      analysis. The determination of the target compounds was achieved in less than
      3.0min using an electrospray ionization source in positive mode (ESI+) for
      furametpyr, pyraclostrobin, and rabenzazole, while negative mode (ESI-) for
      bixafen and fluxapyroxad. The method showed excellent linearity (at least R(2)>=
      0.990) for all studied analytes. The limits of detection were below 3.0 MUg kg(
      1), and the limits of quantification did not exceed 9 MUg kg(-1) in all matrices.
      The overall average recoveries in rice, wheat, cucumber, tomato, lettuce, apple,
      and grape at three levels (10, 100 and 1,000 MUg kg(-1)) were ranged from 70.0%
      to 108% with all RSDs values less than 20.9% for all analytes. The method is
      demonstrated to be convenient and reliable for the routine monitoring of pyrazole
      fungicides in cereals, vegetables and fruits.

PMID- 22999201
TI  - Parallel segmented flow chromatography columns: conventional analytical scale
      column formats presenting as a 'virtual' narrow bore column.
AB  - Narrow bore columns find advantage in HPLC applications when volumetric flow is
      important, For example, for detection processes that are volume limited. Yet
      there are significant drawbacks to narrow bore columns. Due to their small column
      volume relative to analytical scale columns, narrow bore columns are more
      affected by system dead volume. In addition the wall effect and the variation in
      packing density from the centre to the wall are more significant in these columns
      relative to larger scale analytical columns. In this study we operate a 4.6mm
      i.d. parallel segmented flow column in such a manner that it emulates 2.1mm i.d.
      and 3.0mm i.d. columns. By using a parallel segmented flow column in this way, it
      was possible to combine the benefits of narrow bore and analytical scale columns.

PMID- 22999202
TI  - Development of a mathematical model for online microextraction by packed sorbent
      under equilibrium conditions and its application for polycyclic aromatic
      hydrocarbon determination in water by gas chromatography-mass spectrometry.
AB  - In this work, partition equilibriums and extraction rates of different polycyclic
      aromatic hydrocarbons (PAHs) have been calculated by multivariate nonlinear
      regression from data obtained after microextraction by packed sorbent (MEPS) of
      16 PAHs from water samples. The MEPS gas chromatography-mass spectrometry (MEPS
      GC-MS) method has been optimized investigating the partitioning parameters for a
      priori prediction of solute sorption equilibrium, recoveries, pre-concentration
      effects in aqueous and solvent systems. Finally, real samples from sea,
      agricultural irrigation wells, streams and tap water were analyzed. Detection
      (S/N >= 3) and quantification (S/N >= 10) limits were strictly dependent on the
      volume of water and methanol used during the extraction process. Under the
      experimental conditions used, these values range from 0.5 to 2 ngL(-1) and from
      1.6 to 6.2 ngL(-1), respectively. The reasonably good correlation between the
      logarithm of the partition MEPS-water constants (logK(meps/water)) and the
      logarithm of the octanol-water partition coefficients (log K(ow)) (R(2)=0.807)
      allows a rough estimation of K(ow) from the measure of K(meps/water).

PMID- 22999203
TI  - A new application of an aqueous diphase solvent system in one-step preparation of
      polysaccharide from the crude water extract of Radix Astragali by high-speed
      counter-current chromatography.
AB  - Polysaccharide's purification remains challenge to separation technology.
      Conventional methods involve time-consuming and complicated operations and always
      cause significant variation in the isolates' chemistry. This paper reports an
      aqueous diphase solvent system, namely PEG1000-MgSO(4)-H(2)O, which succeeded in
      one-step CCC separation of a polysaccharide (43 mg) from the water extract (1.67
      g) of Radix Astragali. The solvent composition was set as 12:16:72 (w/w/w) of
      which the lower phase was used as the mobile phase at a flow rate of 0.8 mL/min
      in a 1000 mL column. The purified polysaccharide bears an average molecular
      weight of 1095 kDa and consists of galacturonic acid (76.5%), galactose (7.7%),
      arabinose (4.2%) and glucose (5.0%). Methylation analysis result showed it was
      composed of 58.4% of 1,4-linked Glcp, 11.8% of T-linked Araf, 10.5% of T-linked
      Glcp, 9.1% of 1,4,6-linked Galp and 5.1% of 1,3,6-linked Galp, etc. This success
      shows a short way between the crude water extract and purified polysaccharides,
      which minimizes the chemical variation caused by purification methods.

PMID- 22999204
TI  - Preparation of solid-phase microextraction fibers by in-mold coating strategy for
      derivatization analysis of 24-epibrassinolide in pollen samples.
AB  - A novel and simple in-mold coating strategy was proposed for the preparation of
      uniform solid-phase microextraction (SPME) coatings. Such a strategy is based on
      the direct synthesis of the polymer coating on the surface of a solid fiber using
      a glass capillary as the mold. The capillary was removed and the polymer with
      well-controlled thickness could be coated on the silica fiber reproductively.
      Following the strategy, a new poly(acrylamide-co-ethylene glycol dimethacrylate)
      (poly(AM-co-EGDMA)) coating was prepared for the preconcentration of 24
      epibrassinolide (24-epiBL) from plant matrix. The coating had the enrichment
      factor of 32 folds, and the extraction efficiency per unit thickness was 5 times
      higher than that of the commercial polydimethylsiloxane/divinylbenzene (PDMS/DVB)
      coating. A novel method based on SPME coupled with derivatization and large
      volume injection-high performance liquid chromatography (LVI-HPLC) was developed
      for the analysis of 24-epiBL. The linear range was 0.500-20.0 MUg/L with the
      detection limit of 0.13 MUg/L. The amounts of endogenous 24-epiBL in rape and
      sunflower breaking-wall pollens samples were determined with satisfactory
      recovery (77.8-104%) and reproducibility (3.9-7.9%). The SPME-DE/LVI-HPLC method
      is rapid, reliable, convenient and applicable for complicated plant samples.

PMID- 22999205
TI  - On-line coupling of size exclusion chromatography with mixed-mode liquid
      chromatography for comprehensive profiling of biopharmaceutical drug product.
AB  - A methodology based on on-line coupling of size exclusion chromatography (SEC)
      with mixed-mode liquid chromatography (LC) has been developed. The method allows
      for simultaneous measurement of a wide range of components in biopharmaceutical
      drug products. These components include the active pharmaceutical ingredient
      (protein) and various kinds of excipients such as cations, anions, nonionic
      hydrophobic surfactant and hydrophilic sugars. Dual short SEC columns are used to
      separate small molecule excipients from large protein molecules. The separated
      protein is quantified using a UV detector at 280 nm. The isolated excipients are
      switched, online, to the Trinity P1 mixed-mode column for separation, and
      detected by an evaporative light scattering detector (ELSD). Using a stationary
      phase with 1.7 MUm particles in SEC allows for the use of volatile buffers for
      both SEC and mix-mode separation. This facilitates the detection of different
      excipients by ELSD and provides potential for online characterization of the
      protein with mass spectrometry (MS). The method has been applied to quantitate
      protein and excipients in different biopharmaceutical drug products including
      monoclonal antibodies (mAb), antibody drug conjugates (ADC) and vaccines.

PMID- 22999206
TI  - Short-chain fluorescent tryptophan tags for on-line detection of functional
      recombinant proteins.
AB  - BACKGROUND: Conventional fluorescent proteins, such as GFP, its derivatives and
      flavin mononucleotide based fluorescent proteins (FbFPs) are often used as fusion
      tags for detecting recombinant proteins during cultivation. These reporter tags
      are state-of-the-art; however, they have some drawbacks, which can make on-line
      monitoring challenging. It is discussed in the literature that the large
      molecular size of proteins of the GFP family may stress the host cell metabolism
      during production. In addition, fluorophore formation of GFP derivatives is
      oxygen-dependent resulting in a lag-time between expression and fluorescence
      detection and the maturation of the protein is suppressed under oxygen-limited
      conditions. On the contrary, FbFPs are also applicable in an oxygen-limited or
      even anaerobic environment but are still quite large (58% of the size of GFP).
      RESULTS: As an alternative to common fluorescent tags we developed five novel
      tags based on clustered tryptophan residues, called W-tags. They are only 5-11%
      of the size of GFP. Based on the property of tryptophan to fluoresce in absence
      of oxygen it is reasonable to assume that the functionality of our W-tags is also
      given under anaerobic conditions. We fused these W-tags to a recombinant protein
      model, the anti-CD30 receptor single-chain fragment variable antibody (scFv) Ki
      4(scFv) and the anti-MucI single-chain fragment variable M12(scFv). During
      cultivation in Microtiter plates, the overall tryptophan fluorescence intensity
      of all cultures was measured on-line for monitoring product formation via the
      different W-tags. After correlation of the scattered light signal representing
      biomass concentration and tryptophan fluorescence for the uninduced cultures, the
      fluorescence originating from the biomass was subtracted from the overall
      tryptophan signal. The resulting signal, thus, represents the product
      fluorescence of the tagged and untagged antibody fragments. The product
      fluorescence signal was increased. Antibodies with W-tags generated stronger
      signals than the untagged construct. CONCLUSIONS: Our low-molecular-weight W-tags
      can be used to monitor the production of antibody fragments on-line. The binding
      specificity of the recombinant fusion protein is not affected, even though the
      binding activity decreases slightly with increasing number of tryptophan residues
      in the W-tags. Thus, the newly designed W-tags offer a versatile and generally
      applicable alternative to current fluorescent fusion tags.

PMID- 22999207
TI  - No influence of burn size on ventilator-associated pneumonia in burn patients
      with inhalation injury.
AB  - OBJECTIVE: Burn size and inhalation injury are important predictors of mortality
      following burn. The important factors for predicting ventilator-associated
      pneumonia (VAP) following burn remain unclear. The aim of our study was to
      investigate the effect of burn size on VAP in burn patients with inhalation
      injury. METHODS: We retrospectively studied 52 burn patients with inhalation
      injury requiring mechanical ventilation admitted to the Department of Acute
      Medicine, Kawasaki Medical School Hospital, Okayama, Japan, between June 2007 and
      October 2010. RESULTS: The overall mortality for all patients was 15%. Twenty-six
      patients (50%) developed VAP. Patients with VAP required longer ICU stay and
      mechanical ventilation than those without VAP. There was no difference in age,
      gender, mortality, and TBSA between burn patients with inhalation injury with and
      Without VAP. VAP rate had no difference with increasing TBSA in burn patients
      with inhalation injury. CONCLUSIONS: Our data indicated that burn size had no
      relationship with the development of VAP in burn patients with inhalation injury.

PMID- 22999208
TI  - Clinical utility of fungal screening assays in adults with severe burns.
AB  - BACKGROUND: Fungal wound infection is a leading cause of burn wound infections,
      and diagnosis is often delayed as it conventionally requires culture and
      histopathology. Fungal screening assays have sped diagnosis of invasive fungal
      infections in other populations. Few studies have evaluated the performance of
      fungal screening assays outside of the hematologic malignancy and hematopoietic
      stem cell transplant populations. METHODS: We performed a three year
      retrospective analysis of all fungal screening assays in burn patients in the ICU
      between 2008 and 2011. The primary goal was to evaluate the correlation between
      the two available fungal screening assays, (1->3)-beta-d-glucan (BG) and
      galactomannan (GM) assay, and fungal wound colonization (FWC) and infection
      (FWI). We also evaluated previously hypothesized causes of false positives and
      their associations with false positives in the burn population. RESULTS: We
      identified 53 patients [median 29% total body surface area burned (TBSA), IQR 17
      51] with BG or GM serological tests available, of which 15 had a FWI or FWC.
      FWC/FWI was associated with higher TBSA (p=0.02). BG and GM correlated with TBSA
      (BG 0.57, p<0.01; GM 0.35, p=0.02), but neither assay was associated with FWI/FWC
      or species of fungus involved when FWI/FWC was diagnosed. CONCLUSIONS: Positive
      BG and GM fungal screening assays are not associated with FWI/FWC, or with
      species of fungus when FWC/FWI is present. BG false positives are common and
      associated with higher TBSA burns.

PMID- 22999209
TI  - Role of neutrophil elastase in lung injury induced by burn-blast combined injury
      in rats.
AB  - OBJECTIVE: Neutrophil elastase (NE) takes part in the pathogenesis of acute lung
      injury. However, its role in lung injury of burn-blast combined injury is
      unclear. Our objective was to assess the role of NE, and effect of sivelestat, a
      specific NE inhibitor, in lung injury induced by burn-blast combined injury in
      rats. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly
      subjected to burn-blast combined injury (BB) group, burn-blast combined injury
      plus sivelestat treatment (S) group or control (C) group. Blood gas, protein
      concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary
      myeloperoxidase (MPO) activity, serum concentrations of TNF-alpha and IL-8, etc.
      were investigated from 0 h to 7 d post-injury. RESULTS: In BB group, PaO2
      decreased, while NE activity in BALF, total protein concentration in BALF,
      pulmonary MPO activity and W/D ratio, serum concentrations of TNF-alpha and IL-8
      increased with neutrophil infiltration, progressive bleeding and pulmonary
      oedema. Compared with BB group, sivelestat treatment decreased the NE activity
      and ameliorated the above indexes. CONCLUSION: Sivelestat, exerts a protective
      effect in lung injury after burn-blast combined injury through inhibiting NE
      activity to decrease pulmonary vascular permeability, neutrophil sequestration,
      and production of TNF-alpha and IL-8.

PMID- 22999210
TI  - Risk factors for kerosene stove explosion burns seen at Kenyatta National
      Hospital in Kenya.
AB  - BACKGROUND: The kerosene stove is a common cooking appliance in lower and middle
      income households in Kenya and if it explodes, life threatening thermal burn
      injuries may be sustained by those using the appliance. Women tend to be victims
      more frequently since traditionally they are the ones who are involved in
      cooking. OBJECTIVES: The aim of this study was to determine risk factors
      predisposing to kerosene stove explosion burns seen at Kenyatta National
      Hospital. MATERIALS AND METHODS: The study was a prospective longitudinal
      descriptive study carried out at the Kenyatta National Hospital. Forty-eight
      patients who met the inclusion criteria were recruited into the study over a
      period of 6 months from November 2010 to April 2011 and the data was collected
      using a structured questionnaire. The analysis, using SPSS version 17.0 was done
      by associating occurrence of injury to: age, sex, socioeconomic status and level
      of education of patient. Charts and tables were used to present the results.
      RESULTS: The mean age of patients who sustained kerosene stove explosion burns
      was 23.6 years (SD +/- 11.7) with the commonest age group being 20-39 years. More
      females were affected than males by a ratio of 7:3 and ninety two percent of
      those who sustained these burns were either from poor or lower middle socio
      economic class. Stove explosions occurred mainly during cooking and when kerosene
      refill was being done. Most of the patients (63%) reported having bought kerosene
      from fuel vendors and almost all explosions were caused by the wick type of stove
      (98%). CONCLUSION: Young females from poor socioeconomic background were found to
      be at a higher risk for kerosene stove explosion burns. The wick stove is a
      common cause of burns especially when users unwittingly refill it with kerosene
      when already lit resulting in an explosion. Prevention can be done through
      evidence based public health education targeting the groups at risk and enactment
      of relevant laws.

PMID- 22999211
TI  - A new algorithm to allow early prediction of mortality in elderly burn patients.
AB  - INTRODUCTION: The elderly are the fastest growing population segment, and
      particularly susceptible to burns. Predicting outcomes for these patients remains
      difficult. Our objective was to identify early predictors of mortality in elderly
      burn patients. METHODS: Our Burn Center's prospective database was reviewed for
      burn patients 60+ treated in the past 10 years. Predictor variables were
      identified by correlative analysis and subsequently entered into a multivariate
      logistic regression analysis examining survival to discharge. RESULTS: 203
      patients of 1343 (15%) were eligible for analysis. The average age was 72 +/- 10
      (range 60-102) and the average total body surface area (TBSA) burned was 23 +/-
      18% (range 1-95). Age, TBSA, base deficit, pO(2), respiratory rate, Glasgow Coma
      Score (GCS), and Revised Trauma Score (RTS, based on systolic blood pressure,
      respiratory rate, and GCS) all correlated with mortality (p <=0 .05). Using
      multiple logistic regression analysis, a model with age, TBSA and RTS was
      calculated, demonstrating: In this model, beta(0) is a constant that equals 
      8.32. CONCLUSIONS: Predicting outcomes in elderly burn patients is difficult. A
      model using age, TBSA, and RTS can, immediately upon patient arrival, help
      identify patients with decreased chances of survival, further guiding end-of-life
      decisions.

PMID- 22999212
TI  - Red cell antioxidant enzymes and prognostic indexes in patients with burns.
AB  - Red cell superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase
      (CAT) were measured in 66 burned patients (57 men, 9 women, age 16-78 years).
      BSAB varied from 15 to 93% and ABSI from 3 to 14 points. In the first week after
      injury the activity of SOD was significantly decreased as compared with the
      activity of the enzymes in the control group and was also below the reference
      values. Later the activity of SOD increased up to the normal range. The activity
      of CAT followed a similar pattern but the differences were not significant. No
      significant changes in red cell GPX were found during the monitored period. We
      did not find any significant association between the antioxidant enzyme
      activities and the markers of burns severity. On the other side there was a
      significant indirect association between the change of SOD activity (calculated
      as a difference between the first week values after the injury and the activities
      measured later) and BSAB.

PMID- 22999214
TI  - A case of nocturnal frontal lobe epilepsy in a patient with spinocerebellar
      ataxia type 17.

PMID- 22999213
TI  - Daily administration of low molecular weight heparin increases Hepatocyte Growth
      Factor serum levels in gynaecological patients: pharmacokinetic parameters and
      clinical implications.
AB  - BACKGROUND: Hepatocyte Growth Factor (HGF) enhances cytotoxicity of paclitaxel
      (PTX) and cisplatin (CDDP) in human ovarian cancer cells. Because of potential
      pitfalls of HGF exogenous administration, we investigated whether HGF serum
      concentration might be alternatively raised in vivo by administering low
      molecular weight heparin (LMWH). METHODS: The main HGF pharmacokinetic parameters
      were evaluated following acute and chronic LMWH treatment. First, women, operated
      on for gynaecological tumors, were treated with a single dose of calcium
      nadroparin and studied for 12 hours. Next, women operated on for benign or
      malignant gynaecological tumors were treated daily with calcic nadroparin for one
      month. Subsequently, the biological activity of the measured HGF serum levels was
      tested in assays of ovarian cancer cell sensitization to drugs. RESULTS: In the
      short-term treated group, median HGF AUCss, Cmax and Caverage were about four
      fold that of the control group, whereas Cmin was three-fold. In the patients
      treated chronically median HGF serum levels rose about six-fold in the first
      week, and decreased but remained significantly higher after one month. The
      pharmacokinetic of nadroparin-dependent HGF increase were similar in the two
      groups. The HGF concentrations measured after both acute and chronic treatment
      were found to be effective in sensitising ovarian cancer cells to
      chemotherapeutics. CONCLUSIONS: This study raises the possibility of using LMWH
      to increase HGF serum concentration and to take advantage of its biological
      activities. In particular, nadroparin might be used as a chemo-potentiating agent
      in epithelial cell ovarian carcinoma through its action on HGF serum
      concentration. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01523652.

PMID- 22999215
TI  - Computerized cognitive testing in epilepsy (CCTE): a new method for cognitive
      screening.
AB  - PURPOSE: Optimized therapy in epilepsy should include individual care for
      cognitive functions. Here we introduce a computerized screening instrument,
      called "Computerized Cognitive Testing in Epilepsy" (CCTE), which allows for time
      efficient repetitive assessment of the patient's cognitive profile regarding the
      domains of memory and attention, which are frequently impaired due to side
      effects of antiepileptic medication. METHODS: The CCTE battery takes 30min and
      covers tasks of verbal and figural memory, cognitive speed, attention and working
      memory. The patient's results are displayed immediately in comparison to age
      related normative data. For evaluation of psychometrics and clinical
      correlations, data from patients of a tertiary referral epilepsy center (n=240)
      and healthy subjects (n=83) were explored. RESULTS: CCTE subtests show good
      reliability and concurrent validity compared to standard neuropsychological tests
      (p<0.01). Adverse cognitive effects of antiepileptic medication can be detected
      (p<0.05), e.g. significant negative effects of increasing drug load. Specific
      epilepsy subgroups, e.g. focal versus primary generalized epilepsy or right
      versus left mesial temporal lobe epilepsy, showed different CCTE profiles.
      CONCLUSION: CCTE appears valuable for early detection of individual cognitive
      alterations related to medication. In addition, it displays interesting
      differences between epilepsy syndromes. The CCTE battery provides a standardized,
      time- and personnel-efficient assessment of cognitive functions open to a large
      number of patients and applicable for clinical and scientific use in epilepsy.

PMID- 22999216
TI  - Contralateral insular involvement producing false lateralizing signs in
      bitemporal epilepsy: a stereo-encephalography case report.

PMID- 22999217
TI  - Plant experimental biology is an endless adventure.

PMID- 22999218
TI  - New insights into signalling networks regulating breast cancer stem cells.
AB  - In a recent paper, Aceto and colleagues report that Src homology 2 domain
      containing protein tyrosine phosphatase 2 (Shp2) plays a critical role in
      maintenance of breast tumour-initiating cells, and they define novel effectors
      downstream of Shp2 that regulate cellular invasion and self-renewal, including
      the transcription factors c-Myc and zinc finger E-box binding homeobox 1 and the
      suppressor of miRNA biogenesis lin-28 homolog B. These findings provide important
      mechanistic insights into breast tumourigenesis and highlight Shp2 as a potential
      therapeutic target. 

PMID- 22999219
TI  - Synthesis of 3D nanostructured metal alloy of immiscible materials induced by
      megahertz-repetition femtosecond laser pulses.
AB  - : In this work, we have proposed a concept for the generation of three
      dimensional (3D) nanostructured metal alloys of immiscible materials induced by
      megahertz-frequency ultrafast laser pulses. A mixture of two microparticle
      materials (aluminum and nickel oxide) and nickel oxide microparticles coated onto
      an aluminum foil have been used in this study. After laser irradiation, three
      different types of nanostructure composites have been observed: aluminum embedded
      in nickel nuclei, agglomerated chain of aluminum and nickel nanoparticles, and
      finally, aluminum nanoparticles grown on nickel microparticles. In comparison
      with current nanofabrication methods which are used only for one-dimensional
      nanofabrication, this technique enables us to fabricate 3D nanostructured metal
      alloys of two or more nanoparticle materials with varied composite concentrations
      under various predetermined conditions. This technique can lead to promising
      solutions for the fabrication of 3D nanostructured metal alloys in applications
      such as fuel-cell energy generation and development of custom-designed,
      functionally graded biomaterials and biocomposites.

PMID- 22999220
TI  - Defective efferocytosis by alveolar macrophages in IPF patients.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive
      fibrosing interstitial pneumonia. The pathogenicity of IPF has been widely
      investigated but still remains to be clarified. Efferocytosis, the specialized
      recognition and ingestion of apoptotic cells by phagocytes, is essential for the
      resolution of inflammation in the lungs and repair of injured tissues. Impaired
      efferocytosis contributes to the pathogenesis of chronic lung diseases such as
      emphysema and cystic fibrosis. We hypothesized that efferocytosis would also be
      reduced in alveolar macrophages isolated from subjects with IPF. METHODS:
      Efferocytosis, was evaluated using Wright-Giemsa stained cell preparations
      isolated from the bronchoalveolar lavage (BAL) fluid of patients with IPF (n =
      5), nonspecific interstitial pneumonitis (n = 6), cryptogenic organizing
      pneumonia (n = 4) and eosinophilic pneumonia (EP) (n = 5). RESULTS: Uningested
      apoptotic cells were significantly higher in BAL fluid from patients with IPF
      compared to other forms of interstitial lung disease. Macrophages isolated from
      patients with eosinophilic pneumonia had significantly fewer phagocytic
      ingestions than macrophages from the other three groups. CONCLUSION:
      Efferocytosis by alveolar macrophages was significantly lower in subjects with
      IPF compared to subjects with other interstitial pneumonia. Dysregulated
      efferocytosis may contribute to the pathogenesis of IPF.

PMID- 22999221
TI  - Statistical analysis in pharmacology is not always BO.

PMID- 22999222
TI  - Optimization of chemical structure of Schottky-type selection diode for crossbar
      resistive memory.
AB  - The electrical performances of Pt/TiO(2)/Ti/Pt stacked Schottky-type diode (SD)
      was systematically examined, and this performance is dependent on the chemical
      structures of the each layer and their interfaces. The Ti layers containing a
      tolerable amount of oxygen showed metallic electrical conduction characteristics,
      which was confirmed by sheet resistance measurement with elevating the
      temperature, transmission line measurement (TLM), and Auger electron spectroscopy
      (AES) analysis. However, the chemical structure of SD stack and resulting
      electrical properties were crucially affected by the dissolved oxygen
      concentration in the Ti layers. The lower oxidation potential of the Ti layer
      with initially higher oxygen concentration suppressed the oxygen deficiency of
      the overlying TiO(2) layer induced by consumption of the oxygen from TiO(2)
      layer. This structure results in the lower reverse current of SDs without
      significant degradation of forward-state current. Conductive atomic force
      microscopy (CAFM) analysis showed the current conduction through the local
      conduction paths in the presented SDs, which guarantees a sufficient forward
      current density as a selection device for highly integrated crossbar array
      resistive memory.

PMID- 22999223
TI  - [Diagnosis, prevention and treatment of cardiac allograft vasculopathy].
AB  - The major limitation of long-term survival after cardiac transplantation is
      allograft vasculopathy, which consists of concentric and diffuse intimal
      hyperplasia. The disease still has a significant incidence, estimated at 30% five
      years after cardiac transplantation. It is a clinically silent disease and so
      diagnosis is a challenge. Coronary angiography supplemented by intravascular
      ultrasound is the most sensitive diagnostic method. However, new non-invasive
      diagnostic techniques are likely to be clinically relevant in the future. The
      earliest possible diagnosis is essential to prevent progression of the disease
      and to improve its prognosis. A new nomenclature for allograft vasculopathy has
      been published in July 2010, developed by the International Society for Heart and
      Lung Transplantation (ISHLT), establishing a standardized definition.
      Simultaneously, the ISHLT published new guidelines standardizing the diagnosis
      and management of cardiac transplant patients. This paper reviews contemporary
      concepts in the pathophysiology, diagnosis, prevention and treatment of allograft
      vasculopathy, highlighting areas that are the subject of ongoing research.

PMID- 22999224
TI  - Learning from Taiwan patient-safety reporting system.
AB  - OBJECTIVE: The aim of this study is to create a national database to record
      incidents that endanger patient safety. We try to identify systemic problems in
      hospitals in order to avoid safety incidents in the future and improve the
      quality of healthcare. METHOD: The Taiwan Patient Safety Reporting System employs
      a voluntary notification model. We define 13 types of patient safety incidents,
      and the reports of different types of incidents are recorded using common
      terminology. Statistical analysis is used to identify the incident type, time of
      occurrence, location, person who reported the incident, and possible reasons for
      frequently occurring incidents. RESULTS: There were 340 hospitals that joined
      this program from 2005 to 2010. Over 128,271 incident events were reported and
      analyzed. The three most common incidents were drug-related incidents, falls, and
      endo tube related incidents. By analyzing the time of occurrence of incidents, we
      found that drug-related incidents usually occurred between 8 and 10 am. Falls and
      endo tube incidents usually occurred between 4 and 6 am. The most common location
      was wards (57.6%), followed by intensive care areas (13.5%), and pharmacies
      (9.1%). Among hospital staff, nurses reported the highest number of incidents
      (68.9%), followed by pharmacists (14.5%) and administrative staff (5.5%). The
      number of incidents reported by doctors was much lower (1.2%). Most staff members
      who reported incidents had been working for less than five years (58.1%).
      CONCLUSION: The unified reporting system was found to improve the recording and
      analysis of patient safety incidents. To encourage hospital staff to report
      incidents, hospitals need to be assisted in establishing an internal report and
      management system for safety incidents. Hospitals also need a protection
      mechanism to allow staff members to report incidents without the fear of
      punishment. By identifying the root causes of safety incidents and sharing the
      lessons learned across hospitals is the only way such incidents can be stopped
      from happening again.

PMID- 22999226
TI  - Emergency surgery data and documentation reporting forms for sudden-onset
      humanitarian crises, natural disasters and the existing burden of surgical
      disease.
AB  - Following large-scale disasters and major complex emergencies, especially in
      resource-poor settings, emergency surgery is practiced by Foreign Medical Teams
      (FMTs) sent by governmental and non-governmental organizations (NGOs). These
      surgical experiences have not yielded an appropriate standardized collection of
      data and reporting to meet standards required by national authorities, the World
      Health Organization, and the Inter-Agency Standing Committee's Global Health
      Cluster. Utilizing the 2011 International Data Collection guidelines for surgery
      initiated by Medecins Sans Frontieres, the authors of this paper developed an
      individual patient-centric form and an International Standard Reporting Template
      for Surgical Care to record data for victims of a disaster as well as the co
      existing burden of surgical disease within the affected community. The data
      includes surgical patient outcomes and perioperative mortality, along with
      referrals for rehabilitation, mental health and psychosocial care. The purpose of
      the standard data format is fourfold: (1) to ensure that all surgical providers,
      especially from indigenous first responder teams and others performing emergency
      surgery, from national and international (Foreign) medical teams, contribute
      relevant and purposeful reporting; (2) to provide universally acceptable forms
      that meet the minimal needs of both national authorities and the Health Cluster;
      (3) to increase transparency and accountability, contributing to improved
      humanitarian coordination; and (4) to facilitate a comprehensive review of
      services provided to those affected by the crisis.

PMID- 22999225
TI  - Is intensive measurement of body image reactive? A two-study evaluation using
      Ecological Momentary Assessment suggests not.
AB  - Intensive assessment methods (e.g., Ecological Momentary Assessment [EMA]) are
      increasingly used to capture body image experiences in daily life. One concern
      with EMA is multiple assessments may increase reactivity to internal or external
      cues, potentially biasing measurement. Reactivity to EMA was evaluated in two
      studies (Study 1: N=63 female undergraduates, Study 2: N=131 women with high body
      dissatisfaction/disordered eating). Participants completed five daily surveys on
      handheld computers for 1-2 weeks and body image-related questionnaires at the
      start and end of each study. Results showed no systematic changes in pre- and
      post-EMA measures or momentary EMA reports, suggesting women were not reactive to
      the EMA protocols. Completing 1-2 weeks of EMA does not appear to affect body
      dissatisfaction, mood, or attitudes in non-clinical or at-risk samples of women.
      These studies provide evidence that EMA methods can be used to assess real-world
      body image experiences without undue concern about measurement reactivity.

PMID- 22999227
TI  - Speech-language pathologists' knowledge of genetics: perceived confidence,
      attitudes, knowledge acquisition and practice-based variables.
AB  - The purpose of this study was to determine (a) the general knowledge bases
      demonstrated by school-based speech-language pathologists (SLPs) in the area of
      genetics, (b) the confidence levels of SLPs in providing services to children and
      their families with genetic disorders/syndromes, (c) the attitudes of SLPs
      regarding genetics and communication disorders, (d) the primary sources used by
      SLPs to learn about genetic disorders/syndromes, and (e) the association between
      general knowledge, confidence, attitudes, the number of years of experience
      working as an SLP, and the number of children currently provided services with
      genetic disorders/syndromes on SLPs' caseloads. Survey data from a nationwide
      sample of 533 SLPs was analyzed. Results showed SLPs earned a median knowledge
      score about genetics of 66% correct responses. Their mean confidence and attitude
      ratings were in the "unsure" categories while they reported they learned about
      genetics from three main sources, (a) self-study via web and internet-based
      searches, (b) on-the-job training and (c) popular press magazines and newspapers.
      Analyses revealed that Confidence summary scores, Attitude Summary scores, the
      number of children with genetic disorders/syndromes on SLPs' caseloads are
      positively associated with the ratings of participants with the highest Knowledge
      scores. LEARNING OUTCOMES: Readers will be able to (a) explain the important
      links between developmental and communication disabilities and genetics, (b)
      describe the associations between knowledge about genetics and confidence,
      attitudes, and the number of children with genetic disorders/syndromes on their
      caseloads, and (c) outline the clinical and theoretical implications of the
      results from this study.

PMID- 22999228
TI  - Neighborhood characteristics and depressive symptoms of older people: local
      spatial analyses.
AB  - Depressive symptoms in community-dwelling older people significantly increase the
      risk of developing clinically diagnosable depressive disorders. Knowledge of the
      spatial distribution of depressive symptoms in the older population can add
      important information to studies of neighborhood contextual factors and mental
      health outcomes, but analysis of spatial patterns is rarely undertaken. This
      study uses spatial statistics to explore patterns of clustering in depressive
      symptoms using data from a statewide survey of community-dwelling older people in
      New Jersey from 2006 to 2008. A significant overall pattern of clustering in
      depressive symptoms was observed at the state level. In a subsequent local
      clustering analysis, places with high levels of depressive symptoms near to other
      places with high levels of depressive symptoms were identified. The relationships
      between the level of depressive symptoms in a place and poverty, residential
      stability and crime were analyzed using geographically weighted regression.
      Significant local parameter estimates for the three independent variables were
      observed. Local parameters for the poverty variable were positive and significant
      almost everywhere in the state. The significant local parameters for residential
      stability and crime varied in their association with depressive symptoms in
      different regions of the state. This study is among the first to examine spatial
      patterns in depressive symptoms among community-dwelling older people, and it
      demonstrates the importance of exploring spatial variations in the relationships
      between neighborhood contextual factors and health outcomes.

PMID- 22999229
TI  - Social networks of experientially similar others: formation, activation, and
      consequences of network ties on the health care experience.
AB  - Research documents that interactions among experientially similar others
      (individuals facing a common stressor) shape health care behavior and ultimately
      health outcomes. However, we have little understanding of how ties among
      experientially similar others are formed, what resources and information flows
      through these networks, and how network embeddedness shapes health care behavior.
      This paper uses in-depth interviews with 76 parents of pediatric cancer patients
      to examine network ties among experientially similar others after a serious
      medical diagnosis. Interviews were conducted between August 2009 and May 2011.
      Findings demonstrate that many parents formed ties with other families
      experiencing pediatric cancer, and that information and resources were exchanged
      during the everyday activities associated with their child's care. Network flows
      contained emotional support, caregiving strategies, information about second
      opinions, health-related knowledge, and strategies for navigating the health care
      system. Diffusion of information, resources, and support occurred through
      explicit processes (direct information and support exchanges) and implicit
      processes (parents learning through observing other families). Network flows
      among parents shaped parents' perceptions of the health care experience and their
      role in their child's care. These findings contribute to the social networks and
      social support literatures by elucidating the mechanisms through which network
      ties among experientially similar others influence health care behavior and
      experiences. 

PMID- 22999230
TI  - Fatal doxepin intoxication--suicide or slow gradual intoxication?
AB  - The differentiation of intoxication courses is one of the most difficult
      challenges for forensic pathologists and toxicologists. The case of a 52-year-old
      female inpatient of a psychiatric clinic with multiple medications who died from
      doxepin intoxication is reported. Concentrations of doxepin metabolites and
      isomers, pharmacokinetic modelling and genotyping of the doxepin-metabolizing
      cytochrome P450 (CYP) enzymes led to the following conclusion: the lethal doxepin
      concentration of 2100 ng/mL was more likely to have been reached due to drug
      interactions and genetic peculiarities leading to a reduction of the metabolic
      capacity and not by an acute (suicidal) overdose.

PMID- 22999231
TI  - Application of energy dispersive X-ray fluorescence spectrometry (EDX) in a case
      of methomyl ingestion.
AB  - We applied energy dispersive X-ray fluorescence spectrometry (EDX) in a case of
      poisoning by methomyl, a carbamate pesticide. Quantitative GC/MS analysis showed
      that the concentration of methomyl-oxime in the femoral blood was 4.0 MUg/ml. The
      elemental analysis by EDX identified the high peak of silicon and sulfur in the
      stomach contents. We concluded that the cause of his death was methomyl
      poisoning. This indicates that screening of stomach contents by EDX provides
      useful information for the forensic diagnosis.

PMID- 22999232
TI  - Sudden unexpected death in epilepsy: Evaluation of forensic autopsy cases.
AB  - Epilepsy is a common chronic neurological disorder characterized by seizures.
      Mortality is significantly increased in patients with epilepsy. Sudden unexpected
      death in epilepsy (SUDEP) is the most common seizure-related category of death. A
      retrospective study of forensic autopsy cases from 2007 to 2009 at the Office of
      the Chief Medical Examiner (OCME) yielded a total of 104 sudden unexpected deaths
      directly or indirectly caused by an epilepsy/seizure disorder in the State of
      Maryland. Of these deaths, 74 cases met a general accepted definition of SUDEP.
      The age of SUDEP individuals ranged from 14 to 63 with the majority of subjects
      in the ages between 21 and 50 years (58 cases, 78.4%). Males were slightly more
      likely than females to die of SUDEP (male:female=1.5:1 based on the rate). The
      onset age of epilepsy was documented in 47.3% of cases (35/74) based on
      investigation and medical records. Of the 35 cases, 12 subjects had early onset
      epilepsy (onset ages 1-15 years) and 20 subjects had duration of epilepsy for
      more than 10 years. The majority of deaths (61 of the 74 cases, 82.4%) were
      unwitnessed. Death scene investigation showed that 71 deaths (95.9%) occurred
      inside their residence with 50 subjects (70.4%) found either in bed or on the
      bedroom floor near the bed. Forty-three out of 74 cases (58.1%) showed
      neuropathological lesions. Per history, 50 subjects were reported as being on
      anti-epileptic drugs (AEDs). However, postmortem toxicological analysis revealed
      that only 26 subjects (35.1%) had detectable AEDs. Of the 74 cases, seizure
      disorder or epilepsy was listed as primary cause of death in 66 cases and the
      term of SUDEP as official cause of death in only 8 cases. This report focuses on
      the characteristics of death scene investigation and postmortem examination
      findings of SUDEP cases.

PMID- 22999233
TI  - Interaction of bullets with intermediate targets: material transfer and damage.
AB  - In complex shooting incidents, it is not always clear which bullet hit or
      eventually killed the victim and who fired it. The examination of traces of
      foreign material embedded in or adhered to bullets provides critical information
      in the trajectory reconstruction of spent bullets. Such a reconstruction can have
      considerable legal implications because it can prove that it was not someone's
      intention to kill. However, the microtraces that remain on spent bullets are
      often ignored. Microtraces on bullets, around bullet-holes and on ricochet marks
      were investigated using SEM/EDX for two different types of bullets: a relatively
      hard, full metal jacket (FMJ) bullet and a relatively soft, lead round-nose (LRN)
      bullet. A total of 179 bullets were fired into intermediate targets, sheets of 5
      different materials (MDF, greenboard, gypsum fibreboard, glass and steel), at
      approximate incident angles of 90 degrees , 10 degrees  and 5 degrees . Of the
      144 bullets fired at incident angles of 90 degrees , 130 bullets perforated one
      of the materials, and 14 bullets perforated two of the materials. The 35 bullets
      fired at incident angles of 10 degrees  and 5 degrees  ricocheted off the
      intermediate targets, producing ricochet marks. In the majority of cases, traces
      from the target materials were found on the bullet, both after perforation and
      ricochet. The only exceptions were (1) the perforation of 9-mm sheets of MDF by
      FMJ bullets and (2) ricochet off glass when the glass did not break. Steel
      targets transfer small, but still detectable traces of iron to the bullet. The
      order in which targets are hit was reflected in the traces found on the bullets,
      i.e., materials from a secondary target were deposited on top of deposits from
      the primary target. This result implies that it is possible to determine the
      order of impact from the stratification of the material analysed. Traces from the
      bullets were found around all the bullet holes. Wipe-off from lead bullets is
      sometimes visible by the naked eye. Ricocheting bullets produce remarkable traces
      on glass. The combination of sliding and flattening action leaves a trace of the
      bullet's surface material in the form of tiny droplets and other evidence of
      liquid formation. In general, softer LRN bullets are more susceptible to the
      transfer of material than harder FMJ bullets. For perforation, trace materials
      are preferentially deposited in a ring-shaped area around the (flattened or
      unflattened) nose of the bullet.

PMID- 22999234
TI  - Bipartite and tripartite Cucumber mosaic virus-based vectors for producing the
      Acidothermus cellulolyticus endo-1,4-beta-glucanase and other proteins in non
      transgenic plants.
AB  - BACKGROUND: Using plant viruses to produce desirable proteins in plants allows
      for using non-transgenic plant hosts and if necessary, the ability to make rapid
      changes in the virus construct for increased or modified protein product yields.
      The objective of this work was the development of advanced CMV-based protein
      production systems to produce Acidothermus cellulolyticus endo-1, 4-beta
      glucanase (E1) in non-transgenic plants. RESULTS: We used two new Cucumber mosaic
      virus (CMV)-based vector systems for producing the green fluorescent protein
      (GFP) and more importantly, the Acidothermus cellulolyticus endo-1, 4-beta
      glucanase (E1) in non-transgenic Nicotiana benthamiana plants. These are the
      inducible CMVin (CMV-based inducible) and the autonomously replicating CMVar (CMV
      based advanced replicating) systems. We modified a binary plasmid containing the
      complete CMV RNA 3 cDNA to facilitate insertion of desired sequences, and to give
      modifications of the subgenomic mRNA 4 leader sequence yielding several variants.
      Quantitative RT-PCR and immunoblot analysis showed good levels of CMV RNA and
      coat protein accumulation for some variants of both CMVin and CMVar. When genes
      for E1 or GFP were inserted in place of the CMV coat protein, both were produced
      in plants as shown by fluorescence (GFP) and immunoblot analysis. Enzymatic
      activity assays showed that active E1 was produced in plants with yields up to ~
      11 MUg/g fresh weight (FW) for specific variant constructs. We also compared in
      vitro CMV genomic RNA reassortants, and CMV RNA 3 mutants which lacked the C'
      terminal 33 amino acids of the 3A movement protein in attempts to further
      increase E1 yield. Taken together specific variant constructs yielded up to ~21
      MUg/g FW of E1 in non-transgenic plants. CONCLUSIONS: Intact, active E1 was
      rapidly produced in non-transgenic plants by using agroinfiltration with the CMV
      based systems. This reduces the time and cost compared to that required to
      generate transgenic plants and still gives the comparable yields of active E1.
      Our modifications described here, including manipulating cloning sites for
      foreign gene introduction, enhance the ease of use. Also, N. benthamiana, which
      is particularly suitable for agroinfiltration, is a very good plant for transient
      protein production.

PMID- 22999235
TI  - Biochemical basis and clinical consequences of glucolipotoxicity: a primer.
AB  - Both glucose and fatty acids may have good/adaptive or toxic/maladaptive actions
      on the pancreatic beta cell, depending on their concentrations. Hyperglycemia,
      via metabolic intermediates, may result in multiple cellular effects that are
      toxic to the pancreatic beta cell and indeed other tissues. While free fatty
      acids may affect cellular processes beyond lipid metabolism by interacting with
      transcription factors, triglyceride rich lipoproteins are endothelial cell-toxic
      and facilitate atherogenesis. The paradigm of "glucolipotoxicity" espouses that
      increased glucose and fatty acid levels act synergistically in causing toxicity
      to pancreatic islets and other organs, a process that eventually leads to the
      multiple defects seen in the metabolic syndrome and diabetes mellitus.

PMID- 22999236
TI  - Glucose control and cardiovascular outcomes in individuals with diabetes
      mellitus: lessons learned from the megatrials.
AB  - Glucose lowering should be approached by managing overall cardiovascular risk.
      Glycemic goals should be individualized based on duration of diabetes,
      preexisting cardiovascular disease, age, and life expectancy. Intensive glycemic
      control has consistently been shown to produce a substantial benefit for
      preventing long-term microvascular complications in both type 1 and type 2
      diabetes mellitus. Although cardiovascular disease is the major cause of death in
      patients with diabetes, microvascular complications cause substantial morbidity
      and disability. Thus, it is apparent that additional strategies on multimodal
      treatment options are necessary to promote effective management and prevention of
      diabetic complications.

PMID- 22999238
TI  - Insulin sensitization therapy and the heart: focus on metformin and
      thiazolidinediones.
AB  - Chronic heart failure (CHF) is an insulin-resistant (IR) state and the degree of
      IR is related to disease severity and poor clinical outcome in CHF. IR may be
      pathophysiologically linked with CHF. Therefore, IR may represent a new target
      for treatment in CHF. Metformin and thiazolidinediones (TZDs) are effective
      diabetic therapies that are insulin sensitizers. TZDs are contraindicated in CHF
      because their use is associated with increased incidence of CHF as a result of
      their effects on renal sodium reabsorption and vascular permeability. There is
      evidence to suggest that metformin may be both safe and useful in CHF.

PMID- 22999239
TI  - Diabetes mellitus and myocardial mitochondrial dysfunction: bench to bedside.
AB  - In diabetics, the risk for development of heart failure is increased even after
      adjusting for coronary artery disease and hypertension. Although the cause of
      this increased heart failure risk is multifactorial, increasing evidence suggests
      that dysfunction of myocardial mitochondria represents an important pathogenetic
      factor. To date, no specific therapy exists to treat mitochondrial function in
      any cardiac disease. This article presents underlying mechanisms of mitochondrial
      dysfunction in the diabetic heart and discusses potential therapeutic options
      that may attenuate these mitochondrial derangements.

PMID- 22999240
TI  - Postprandial dysmetabolism and the heart.
AB  - Epidemiologic evidence indicates that abnormal elevations in glycemia and
      lipidemia after a meal, termed postprandial dysmetabolism, are linked with
      increased risk of morbidity and mortality due to cardiovascular disease in
      individuals with or without type 2 diabetes. Both postprandial hyperglycemia and
      postprandial hyperlipidemia are independently associated with deteriorating
      endothelial function and vascular damage, which are likely mediated by increased
      oxidative stress and are more pronounced when both derangements coexist.
      Pharmacotherapies that target postprandial hyperglycemia and/or postprandial
      dyslipidemia are likely to improve endothelial function, which may have positive
      implications for cardiovascular outcomes.

PMID- 22999237
TI  - Glycemic variability and glycemic control in the acutely ill cardiac patient.
AB  - The mechanisms for hyperglycemia-mediated harm in the hospitalized cardiac
      patient are poorly understood. Potential obstacles in the inpatient management of
      hyperglycemia in cardiac patients include rapidly changing clinical status,
      frequent procedures and interruptions in carbohydrate exposure, and short
      hospital length of stay. A patient's preadmission regimen is rarely suitable for
      inpatient glycemic control. Instead, an approach to a flexible, physiologic
      insulin regimen is described, which is intended to minimize glycemic excursions.
      When diabetes or hyperglycemia is addressed early and consistently, the hospital
      stay can serve as a potential window of opportunity for reinforcing self-care
      behaviors that reduce long-term complications.

PMID- 22999241
TI  - Insulin resistance and atherosclerosis.
AB  - Insulin resistance is a complex metabolic defect that has several causes
      dependent on an individual's genetic substrate and the underlying
      pathophysiologic state. Atherogenic dyslipidemia, hyperinsulinemia, dysglycemia,
      inflammation associated with obesity, and ectopic steatosis in liver and skeletal
      muscle all collude to facilitate endothelial dysfunction and predispose to the
      initiation and propagation of atherosclerosis. As aggressive management of the
      various risk factors does not seem to abrogate the so-called residual risk, more
      research is needed to define ways by which intervention can fundamentally alter
      the metabolic and vascular milieu and slow the pace of atherosclerosis, thus
      favorably affecting outcomes.

PMID- 22999243
TI  - Insulin resistance and heart failure: molecular mechanisms.
AB  - This article addresses the issue of insulin resistance and associated reductions
      in cardiac insulin metabolic signaling, which is emerging as a major factor in
      the development of heart failure, and assumes more importance because of an
      epidemic increase in obesity and the cardiorenal metabolic syndrome in our aging
      population. The effects of cardiac insulin resistance are exacerbated by
      metabolic, endocrine, and cytokine alterations associated with systemic insulin
      resistance. Understanding the molecular mechanisms linking insulin resistance and
      heart failure may help to design new and more effective mechanism-based drugs to
      improve myocardial and systemic insulin resistance.

PMID- 22999242
TI  - Role of lipotoxicity in endothelial dysfunction.
AB  - Vascular endothelial dysfunction is determined by both genetic and environmental
      factors that cause decreased bioavailability of the vasodilator nitric oxide.
      This is a hallmark of atherosclerosis, hypertension, and coronary heart disease,
      which are major complications of metabolic disorders, including diabetes and
      obesity. Several therapeutic interventions, including changes in lifestyle as
      well as pharmacologic treatments, are useful for improving endothelial
      dysfunction in the face of lipotoxicity. This review discusses the current
      understanding of molecular and physiologic mechanisms underlying lipotoxicity
      mediated endothelial dysfunction as well as relevant therapeutic approaches to
      ameliorate dyslipidemia and consequent endothelial dysfunction that have the
      potential to improve cardiovascular and metabolic outcomes.

PMID- 22999246
TI  - Myocardial fatty acid metabolism and lipotoxicity in the setting of insulin
      resistance.
AB  - Management of diabetes and insulin resistance in the setting of cardiovascular
      disease has become an important issue in an increasingly obese society. Besides
      the development of hypertension and buildup of atherosclerotic plaques, the
      derangement of fatty acid and lipid metabolism in the heart plays an important
      role in promoting cardiac dysfunction and oxidative stress. This review discusses
      the mechanisms by which metabolic inflexibility in the use of fatty acids as the
      preferred cardiac substrate in diabetes produces detrimental effects on
      mechanical efficiency, mitochondrial function, and recovery from ischemia. Lipid
      accumulation and the consequences of toxic lipid metabolites are also discussed.

PMID- 22999244
TI  - Diabetic cardiomyopathy: bench to bedside.
AB  - The study of diabetic cardiomyopathy is an area of significant interest given the
      strong association between diabetes and the risk of heart failure. Many
      unanswered questions remain regarding the clinical definition and pathogenesis of
      this metabolic cardiomyopathy. This article reviews the current understanding of
      diabetic cardiomyopathy with a particular emphasis on the unresolved issues that
      have limited translation of scientific discovery to patient bedside.

PMID- 22999245
TI  - Sphingolipids, lipotoxic cardiomyopathy, and cardiac failure.
AB  - In the setting of obesity and type 2 diabetes mellitus, the ectopic disposition
      of lipids may be a cause of heart failure. Clinical studies have clearly shown a
      correlation between the accumulation of triglycerides and heart dysfunction. In
      this process, it is likely that there are also changes in the contents of
      sphingolipids. Sphingolipids are important structural and signaling molecules.
      One specific sphingolipid, ceramide, may cause cardiac dysfunction, whereas
      another, sphingosine 1-phosphate, is cardioprotective. In this review, the
      authors focus on the role of sphingolipids in the development and prevention of
      cardiac failure.

PMID- 22999247
TI  - Hepatic and cardiac steatosis: are they coupled?
AB  - Cardiac and hepatic fat are associated with insulin resistance and impaired
      suppression of lipolysis, ultimately leading to lipotoxicity. In the heart the
      lipotoxic effect translates into an impairment of energetic and mechanical
      efficiency, whereas in the liver a fibrogenic response is favored by the
      abundance of inflammatory cells. These features precede, and likely contribute
      to, left ventricular overload and cardiac hypertrophy through mechanisms similar
      to the ones observed in the progression of liver damage in nonalcoholic fatty
      liver disease (NAFLD). Collectively these findings suggest the presence of
      complex and intertwined interrelationships between NAFLD, myocardial steatosis,
      and coronary artery disease.

PMID- 22999248
TI  - Epicardial steatosis, insulin resistance, and coronary artery disease.
AB  - Insulin resistance (IR) is the accepted primary cause of the metabolic syndrome.
      Visceral obesity is inversely correlated with insulin sensitivity.
      Hyperinsulinemia (a surrogate for IR) is highly prevalent in patients with
      coronary artery disease (CAD). Abnormalities in lipid metabolism give rise to
      steatosis in multiple organs. Evidence is rapidly accumulating to show that
      epicardial steatosis and expansion of coronary fat pad volume are highly
      deleterious and associated with increased risk for CAD. This article explores
      such associations from biochemical and structural standpoints, focusing on
      changes in epicardial adiposity.

PMID- 22999249
TI  - beta-blockers in heart failure: breaking tradition to avoid diabetes?

PMID- 22999250
TI  - Glucolipotoxicity and the heart.

PMID- 22999251
TI  - Distribution of human papillomavirus genotype and cervical neoplasia among women
      with abnormal cytology in Beijing, China.
AB  - OBJECTIVE: To understand the relationship between human papillomavirus (HPV)
      genotype distribution and cervical neoplasia among women with abnormal cytology
      in Beijing. METHODS: In a study in Beijing, China, participants underwent a
      gynecologic examination between September 2006 and December 2009. Those with
      abnormal cytology underwent colposcopy, biopsy, and HPV testing. HPV was typed by
      flow-through hybridization on formalin-fixed paraffin-embedded tissue. RESULTS:
      Among 6339 women examined, 533 with abnormal cytology underwent HPV testing. The
      prevalence of high-risk HPV (HR-HPV) subtypes was 29.8%. HPV-16 was the most
      common genotype (12.8%), followed by HPV-33, HPV-58, HPV-66, HPV-18, and HPV-52.
      The cytologic and histopathologic grade clearly increased with a higher
      prevalence of HR-HPV infection. Both HPV-16 and HPV-33 were significantly
      associated with grade CIN2+ lesions (P<0.05). By contrast, HPV-18 and HPV-66 were
      not associated with cervical lesion severity. HR-HPV infection was most common
      among women aged 30-34 years (35.0%). CONCLUSION: HPV-16, HPV-58, HPV-33, HPV-66,
      HPV-18, and HPV-52 were the most common genotypes in Beijing. HPV-16 and HPV-33
      might be associated with CIN2+ lesions. HPV-18 and HPV-66 were not associated
      with high-grade cervical lesions. The present results might help to improve HPV
      vaccination and cervical cancer prevention programs in Beijing.

PMID- 22999252
TI  - Network inference via adaptive optimal design.
AB  - BACKGROUND: Current research in network reverse engineering for genetic or
      metabolic networks very often does not include a proper experimental and/or input
      design. In this paper we address this issue in more detail and suggest a method
      that includes an iterative design of experiments based, on the most recent data
      that become available. The presented approach allows a reliable reconstruction of
      the network and addresses an important issue, i.e., the analysis and the
      propagation of uncertainties as they exist in both the data and in our own
      knowledge. These two types of uncertainties have their immediate ramifications
      for the uncertainties in the parameter estimates and, hence, are taken into
      account from the very beginning of our experimental design. FINDINGS: The method
      is demonstrated for two small networks that include a genetic network for mRNA
      synthesis and degradation and an oscillatory network describing a molecular
      network underlying adenosine 3'-5' cyclic monophosphate (cAMP) as observed in
      populations of Dyctyostelium cells. In both cases a substantial reduction in
      parameter uncertainty was observed. Extension to larger scale networks is
      possible but needs a more rigorous parameter estimation algorithm that includes
      sparsity as a constraint in the optimization procedure. CONCLUSION: We conclude
      that a careful experiment design very often (but not always) pays off in terms of
      reliability in the inferred network topology. For large scale networks a better
      parameter estimation algorithm is required that includes sparsity as an
      additional constraint. These algorithms are available in the literature and can
      also be used in an adaptive optimal design setting as demonstrated in this paper.

PMID- 22999253
TI  - Folk taxonomy and use of mushrooms in communities around Ngorongoro and Serengeti
      National Park, Tanzania.
AB  - BACKGROUND: Maasai and Kurya form two main communities around the Serengeti
      National Park in Tanzania which are mainly pastoralists. Changing climate to
      excessive drought, have recently forced them to start practicing subsistence
      farming which is severely affected by wild animals. This study explored status of
      the folk taxonomy and uses of mushrooms in the two communities as a pave way for
      possibilities of introducing mushroom cultivation, an alternative crop which is
      hardly affected by wild animals. METHODS: Folk taxonomy and use mushrooms by the
      Kurya and Maasai communities were investigated. Information was collected by face
      to face interviews with 150 individuals in 6 selected villages. Using descriptive
      statistics by Statistic Package for the Social Science (SPSS) version 17.0, the
      demographic characteristics of informants were evaluated and cross relationships
      with the recorded data were analysed. RESULTS: Kurya are mycophilic with 94% of
      the informants recognizing utilization of the wild mushroom either as foodstuff
      or as tonics while the Maasai are mycophobic with 99% being unaware of the
      edibility of mushroom although 28% recognized mushrooms as tonic. For both
      communities, the knowledge of mushroom utilization and folk taxonomy increased
      with age of the informants, while it decreases with formal education level of the
      informants which imply that the basis of knowledge is mainly traditional.
      Comparing the two communities, the Maasai use mushrooms only for medicinal
      purposes and never sought them for food while the Kurya were well knowledgeable
      on the edibility and folk classification especially the Termitomyces species.
      Characters used in folkal taxonomy included color and size of the basidiomata,
      shape and size of the pseudorrhiza, habitats and edibility information. A new use
      of ascospores whereby they anaesthaesia bees during honey harvesting was
      discovered, and mushroom cultivation was widely welcomed (94.7%) as an
      alternative crop which is rarely affected by wild animals. CONCLUSION: In order
      to salvage a noted tremendous decrease of knowledge in mushroom utilization and
      folk taxonomy from vanishing, there is a need to document it throughout, and
      incorporate it in lower levels of our education system. Mushroom cultivation may
      possibly be the best alternative crop for the two communities thus should be
      advocated for improving livelihood and reduce human wildlife conflicts. The new
      recorded use of ascospores to anaesthaesia the bees during honey harvesting
      should be exploited and scaled up for sustainable integrated bee keeping and
      mushroom farming.

PMID- 22999254
TI  - [Evaluation of reconstructive techniques after orbital exenteration in 56 cases].
AB  - PURPOSE: To describe the management of orbital exenterations and the surgical
      techniques for the reconstruction of orbital exenteration cavities. PATIENTS AND
      METHODS: This retrospective study includes 56 patients who underwent orbital
      exenteration between 2000 and 2009. Patients' age at the time of exenteration,
      diagnoses, complications and reconstructive techniques were studied. RESULTS:
      Fifty-six patients - 31 male and 25 female patients - who underwent orbital
      exenteration between 2000 to 2009 were included in the study. The mean age was
      62.5 years at the time of exenteration. Average follow-up was 23 months. The
      principal diagnoses were basal cell carcinoma of the eyelids (25%) and
      conjunctival melanoma (20%). For orbital reconstruction, 18 patients (32%) had a
      muscle flap, and 24 patients (43%) underwent secondary reconstruction by bone
      anchored implants after spontaneous epithelialisation of the orbit. Approximately
      50% of the patients received postoperative radiation therapy. DISCUSSION:
      Surgical reconstruction using muscle flaps may mask recurrent tumor.
      Epithelialisation and bone-anchored implants supporting the prosthesis allow for
      recurrent cancer surveillance while providing better stabilization of the
      prosthesis. Radiation therapy seems to render the orbit more fragile and thus
      less stable for implants. CONCLUSION: Orbital exenteration is a mutilating
      technique. Rehabilitation techniques have been improved, in particular the bone
      anchored implants which allow adaptation of the prosthesis with satisfactory
      cosmetic results.

PMID- 22999255
TI  - Requirements for human Dicer and TRBP in microRNA-122 regulation of HCV
      translation and RNA abundance.
AB  - MicroRNA-122 (miR-122) promotes Hepatitis C Virus (HCV) RNA stability,
      accumulation, and translation through hybridization with the 5' untranslated
      region (5' UTR) of the HCV genome. Depletion of Dicer and TRBP, proteins involved
      in miRNA biogenesis, reduced HCV RNA accumulation, mature duplex miR-122
      abundance, and miR-122 directed mRNA translation suppression, suggesting roles in
      miR-122 processing. HCV RNA accumulation independent of endogenous mature duplex
      miR-122 was not affected by Dicer knockdown, suggesting that Dicer is required
      solely for miR-122 biogenesis, but TRBP knockdown reduced HCV RNA accumulation in
      this system, suggesting an additional role in supporting HCV RNA accumulation.
      Mature duplex miR-122 and pre-miR-122 hairpin, but not single-stranded miR-122
      (guide or * strand), augmented HCV RNA accumulation and translation, and Dicer
      and TRBP were essential for the activity of pre-miR-122 in mouse fibroblasts.
      Thus, canonical miRNA processing and strand selection is essential for the
      activity of miR-122 on HCV translation and RNA accumulation.

PMID- 22999257
TI  - Alfalfa mosaic virus replicase proteins, P1 and P2, localize to the tonoplast in
      the presence of virus RNA.
AB  - To identify the virus components important for assembly of the Alfalfa mosaic
      virus replicase complex, we used live cell imaging of Arabidopsis thaliana
      protoplasts that expressed various virus cDNAs encoding native and GFP-fusion
      proteins of P1 and P2 replicase proteins and full-length virus RNAs. Expression
      of P1-GFP alone resulted in fluorescent vesicle-like bodies in the cytoplasm that
      colocalized with FM4-64, an endocytic marker, and RFP-AtVSR2, RabF2a/Rha1
      mCherry, and RabF2b/Ara7-mCherry, all of which localize to multivesicular bodies
      (MVBs), which are also called prevacuolar compartments, that mediate traffic to
      the lytic vacuole. GFP-P2 was driven from the cytosol to MVBs when expressed with
      P1 indicating that P1 recruited GFP-P2. P1-GFP localized on the tonoplast, which
      surrounds the vacuole, in the presence of infectious virus RNA, replication
      competent RNA2, or P2 and replication competent RNA1 or RNA3. This suggests that
      a functional replication complex containing P1, P2, and a full-length AMV RNA
      assembles on MVBs to traffic to the tonoplast.

PMID- 22999258
TI  - The specific infectivity of hepatitis C virus changes through its life cycle.
AB  - Hepatitis C virus (HCV) causes liver diseases, such as hepatitis, liver
      cirrhosis, steatosis, and hepatocellular carcinoma. To understand the life cycle
      and pathogenesis of HCV, the one-step growth of HCV in a cell culture system was
      analyzed using a highly infectious variant of the JFH1 clone. The observed
      profiles of HCV RNA replication indicated that the synthesis of negative-strand
      RNAs occurred at 6 h (h) after infection, followed by the active synthesis of
      positive-strand RNAs. Our measurements of infectious virus production showed that
      the latent period of HCV was about 12 h. The specific infectivity of HCV
      particles (focus-forming unit per viral RNA molecule) secreted to the
      extracellular milieu early in infection was about 30-fold higher than that
      secreted later during infection. The buoyant densities of the infectious virion
      particles differed with the duration of infection, indicating changes in the
      compositions of the virion particles.

PMID- 22999256
TI  - Novel insect-specific flavivirus isolated from northern Europe.
AB  - Mosquitoes collected in Finland were screened for flaviviral RNA leading to the
      discovery and isolation of a novel flavivirus designated Hanko virus (HANKV).
      Virus characterization, including phylogenetic analysis of the complete coding
      sequence, confirmed HANKV as a member of the "insect-specific" flavivirus (ISF)
      group. HANKV is the first member of this group isolated from northern Europe, and
      therefore the first northern European ISF for which the complete coding sequence
      has been determined. HANKV was not transcribed as DNA in mosquito cell culture,
      which appears atypical for an ISF. HANKV shared highest sequence homology with
      the partial NS5 sequence available for the recently discovered Spanish
      Ochlerotatus flavivirus (SOcFV). Retrospective analysis of mitochondrial
      sequences from the virus-positive mosquito pool suggested an Ochlerotatus
      mosquito species as the most likely host for HANKV. HANKV and SOcFV may therefore
      represent a novel group of Ochlerotatus-hosted insect-specific flaviviruses in
      Europe and further afield.

PMID- 22999261
TI  - Does pioglitazone improve depression through insulin-sensitization? Results of a
      randomized double-blind metformin-controlled trial in patients with polycystic
      ovarian syndrome and comorbid depression.
AB  - Thiazolidinediones have shown beneficial effects in short-term treatment of
      depression. However, it is unclear whether the antidepressant efficacy of these
      agents is related to their insulin-sensitizing action. We conducted the present
      study to compare the antidepressant efficacy of pioglitazone with another insulin
      sensitizer, metformin, in obese patients with concomitant polycystic ovarian
      syndrome (PCOS) and major depressive disorder (MDD). In a six-week double-blind
      study, 50 patients with PCOS and MDD (DSM-IV-TR criteria) with Hamilton
      depression rating scale (HDRS) score of <20, randomly received pioglitazone (15
      mg twice daily; PO) or metformin (750 mg twice daily; PO). Assessment was done
      using HDRS (weeks 0, 3, 6) together with fasting Insulin, glucose, and lipid
      profile, liver enzymes, homeostatic model assessment of insulin resistance (HOMA
      IR), anthropometric measures, and serum androgens (weeks 0 and 6). Pioglitazone
      was superior to metformin in reducing HDRS scores at the end of the study [38.3%
      versus 8.3% reduction from baseline scores, F(1, 37) = 73.513, P<0.001]. Changes
      from baseline in HOMA-IR values at week 6 were not significantly different
      between the two groups (P = 0.888). Baseline (but not follow-up) HDRS and HOMA-IR
      values were significantly correlated (r = 0.393, P = 0.012). In multiple
      regression analysis, treatment with pioglitazone independent of HOMA-IR values
      predicted greater score reduction on HDRS at week 6 (standardized beta = 0.801,
      P<0.001). Biochemical and hormonal profile did not differ between the two groups
      at week 6. Metformin was associated with higher frequency of gastrointestinal
      side effects (P = 0.014). In summary, we showed that pioglitazone improved
      depression with mechanisms largely unrelated to its insulin-sensitizing action
      (registration number: IRCT201106081556N23).

PMID- 22999262
TI  - Cortisol reactivity and distress-induced emotional eating.
AB  - Animal studies suggest a relationship between blunted HPA-axis stress reactivity
      and increased stress-induced food intake in chronically stressed animals. Such a
      relationship can potentially explain the underlying mechanisms of emotional
      eating in humans. However, no studies have experimentally tested the relationship
      between stress-induced cortisol responses and acute food intake in high and low
      emotional eaters. We studied these effects in 46 female students that were
      preselected on the basis of extremely high (HEE) or low (LEE) scores on an
      emotional eating questionnaire. Using a within subject design we measured the
      difference of actual food intake after a control or a stress task (Trier Social
      Stress Test). The HEE and LEE groups did not differ in their cortisol stress
      reactivity but emotional eating significantly moderated the relationship between
      cortisol stress reactivity and the difference of food intake after stress vs
      control. Whereas HEE participants with a blunted cortisol stress response ate
      more food after distress than those with an elevated cortisol stress response,
      LEE participants showed no such relationship. These findings support the
      relevance of an animal based model on the relationship between a blunted cortisol
      stress response and increased stress-induced food intake for human high emotional
      eaters.

PMID- 22999263
TI  - Plasma oxytocin distributions in a large cohort of women and men and their gender
      specific associations with anxiety.
AB  - Research has consistently addressed the relations between plasma oxytocin (OT) -
      a nonapeptide implicated in mammalian social bonding - and psychological
      distress, but the direction of the association remains unclear. Utilizing the
      largest sample of plasma OT to date (N=473), the current study had two goals.
      First, we described the distributions of plasma OT in women and men, and second,
      we examined whether the relations between OT and two types of anxiety - trait and
      attachment anxiety - are moderated by gender. Results indicated that OT values
      (M=375.78 pg/ml, SD=264.03, range=51.40-2752.30) clustered around the mean with a
      long right tail, indicating trend toward high values. In most participants
      (N=323), OT was measured again six months after initial assessment and OT levels
      were highly stable within individuals. After removing outliers 2.5 SD above the
      mean (>=1098 pg/ml for men and >=988 pg/ml for women), men showed significantly
      higher mean OT than women (women: 327.13 pg/ml, SD=164.43; men: 399.91,
      SD=183.65; t=2.57, p=.01). Gender was found to moderate the relations between OT
      and anxiety. Trait anxiety was lower among men with higher OT but no such links
      emerged for women, supporting the hypothesized anxiolytic effects of OT in males
      only. Furthermore, women with extreme values (>=988 pg/ml) had three times the
      probability of being classified as highly anxious (STAI-T>=45). Higher OT in
      women correlated with greater attachment anxiety, but no such relationships were
      found for men. Results are consistent with models on the differential
      associations between the neurobiology of attachment and the experience of anxiety
      in women and men.

PMID- 22999264
TI  - Intensity modulated radiation therapy for gynecologic malignancies: a testable
      hypothesis.

PMID- 22999265
TI  - In regard to Roberge et al.

PMID- 22999266
TI  - In reply to Prabhu et Al.

PMID- 22999267
TI  - In reply to Vassiliou and Kountourakis.

PMID- 22999268
TI  - In regard to Samuelian et Al.

PMID- 22999269
TI  - In reply to Hastings and Iganej.

PMID- 22999270
TI  - The return of the snake oil salesmen: the sequel.

PMID- 22999271
TI  - Intensity modulated proton and photon therapy for early prostate cancer with or
      without transperineal injection of a polyethylen glycol spacer: a treatment
      planning comparison study.
AB  - PURPOSE: Rectal toxicity is a serious adverse effect in early-stage prostate
      cancer patients treated with curative radiation therapy (RT). Injecting a spacer
      between Denonvilliers' fascia increases the distance between the prostate and the
      anterior rectal wall and may thus decrease the rectal radiation-induced toxicity.
      We assessed the dosimetric impact of this spacer with advanced delivery RT
      techniques, including intensity modulated RT (IMRT), volumetric modulated arc
      therapy (VMAT), and intensity modulated proton beam RT (IMPT). METHODS AND
      MATERIALS: Eight prostate cancer patients were simulated for RT with or without
      spacer. Plans were computed for IMRT, VMAT, and IMPT using the Eclipse treatment
      planning system using both computed tomography spacer+ and spacer- data sets.
      Prostate +/- seminal vesicle planning target volume [PTV] and organs at risk
      (OARs) dose-volume histograms were calculated. The results were analyzed using
      dose and volume metrics for comparative planning. RESULTS: Regardless of the
      radiation technique, spacer injection decreased significantly the rectal dose in
      the 60- to 70-Gy range. Mean V(70 Gy) and V(60 Gy) with IMRT, VMAT, and IMPT
      planning were 5.3 +/- 3.3%/13.9 +/- 10.0%, 3.9 +/- 3.2%/9.7 +/- 5.7%, and 5.0 +/-
      3.5%/9.5 +/- 4.7% after spacer injection. Before spacer administration, the
      corresponding values were 9.8 +/- 5.4% (P=.012)/24.8 +/- 7.8% (P=.012), 10.1 +/-
      3.0% (P=.002)/17.9 +/- 3.9% (P=.003), and 9.7 +/- 2.6% (P=.003)/14.7% +/- 2.7%
      (P=.003). Importantly, spacer injection usually improved the PTV coverage for
      IMRT. With this technique, mean V(70.2 Gy) (P=.07) and V(74.1 Gy) (P=0.03) were
      100 +/- 0% to 99.8 +/- 0.2% and 99.1 +/- 1.2% to 95.8 +/- 4.6% with and without
      Spacer, respectively. As a result of spacer injection, bladder doses were usually
      higher but not significantly so. Only IMPT managed to decrease the rectal dose
      after spacer injection for all dose levels, generally with no observed increase
      to the bladder dose. CONCLUSIONS: Regardless of the radiation technique, a
      substantial decrease of rectal dose was observed after spacer injection for
      curative RT to the prostate.

PMID- 22999272
TI  - Modeling local control after hypofractionated stereotactic body radiation therapy
      for stage I non-small cell lung cancer: a report from the elekta collaborative
      lung research group.
AB  - PURPOSE: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged
      as an effective treatment option for early-stage non-small cell lung cancer
      (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a
      tumor control probability (TCP) model that predicts 2-year local control after
      SBRT as a function of biologically effective dose (BED) and tumor size. METHODS
      AND MATERIALS: We formulated our TCP model as follows: TCP = e([BED10 - c * L -
      TCD50]/k) / (1 + e([BED10 - c * L - TCD50]/k)), where BED10 is the biologically
      effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50
      and k are parameters that define the shape of the TCP curve. Least-squares
      optimization with a bootstrap resampling approach was used to identify the values
      of c, TCD50, and k that provided the best fit with observed actuarial 2-year
      local control rates. RESULTS: Data from 504 NSCLC tumors treated with a variety
      of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26
      local recurrences were observed. The optimal values for c, TCD50, and k were 10
      Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be
      defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model
      indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95%
      chances of tumor control at 2 years, respectively. When patients were grouped by
      sBED, the model accurately characterized the relationship between sBED and
      actuarial 2-year local control (r=0.847, P=.008). CONCLUSION: We have developed a
      TCP model that predicts 2-year local control rate after hypofractionated SBRT for
      early-stage NSCLC as a function of biologically effective dose and tumor
      diameter. Further testing of this model with additional datasets is warranted.

PMID- 22999273
TI  - iPSC technology to study human aging and aging-related disorders.
AB  - A global aging population, normally accompanied by a high incidence of aging
      associated diseases, has prompted a renewed interest in basic research on human
      aging. Although encouraging progress has been achieved using animal models, the
      underlying fundamental mechanisms of aging remain largely unknown. Here, we
      review the human induced pluripotent stem cell (hiPSC)-based models of aging and
      aging-related diseases. These models seek to advance our knowledge of aging
      molecular mechanisms and help to develop strategies for treating aging-associated
      human diseases.

PMID- 22999274
TI  - Undiagnosed submucous cleft palate interfering with inhalation therapy and a
      solution.
AB  - Patients with velopharyngeal insufficiency who require inhalation therapy should
      be advised to hold their noses when inhaling medication to ensure that they
      receive the dosage prescribed.

PMID- 22999275
TI  - Total knee arthroplasty in patients with a left ventricular assist device.
AB  - Many patients with severe cardiac disease can now live for a prolonged period
      with left ventricular assist devices (LVADs), and some patients will develop
      noncardiac medical issues that may benefit from surgical intervention. Previous
      studies have reported a low rate of complications in patients with LVADs
      undergoing noncardiac surgical procedures. We report the cases of 2 patients with
      LVADs who underwent total knee arthroplasties for osteoarthritis. Both patients
      had significant pain relief and improved function; however, management of
      anticoagulation and bleeding complications was challenging.

PMID- 22999276
TI  - Short communication: Estimates of heritabilities and genetic correlations among
      milk fatty acid unsaturation indices in Canadian Holsteins.
AB  - The objectives of the present study were to estimate genetic parameters of milk
      fatty acid unsaturation indices in Canadian Holsteins. Data were available on
      milk fatty acid composition of 2,573 Canadian Holstein cows from 46 commercial
      herds enrolled in the Quebec Dairy Production Centre of Expertise, Valacta
      (Sainte-Anne-de-Bellevue, Quebec, Canada). Individual fatty acid percentages
      (g/100 g of total fatty acids) were determined for each milk sample by gas
      chromatography. The unsaturation indices were calculated as the ratio of an
      unsaturated fatty acid to the sum of that unsaturated fatty acid and its
      corresponding substrate fatty acid, multiplied by 100. A mixed linear model was
      fitted under REML for the statistical analysis of milk fatty acid unsaturation
      indices. The statistical model included the fixed effects of parity, age at
      calving, and stage of lactation, each nested within parity, and the random
      effects of herd-year-season of calving, animal, and residual. Estimates of
      heritabilities for the C14, C16, C18, conjugated linoleic acid, and total
      unsaturation indices were 0.48, 0.25, 0.29, 0.14, and 0.19, respectively.
      Phenotypic and genetic correlation estimates among unsaturation indices were all
      positive and ranged from 0.20 to 0.65 and 0.23 to 0.81, respectively. The
      estimates of heritabilities and genetic correlations for milk fatty acid
      unsaturation indices suggest that genetic variation exists among cows in milk
      fatty acid unsaturation, and the proportions of desirable unsaturated fatty acids
      from a human health point of view may be increased in bovine milk through genetic
      selection.

PMID- 22999277
TI  - Effect of abomasal infusion of oligofructose on portal-drained visceral ammonia
      and urea-nitrogen fluxes in lactating Holstein cows.
AB  - The effects of abomasal infusion of oligofructose in lactating dairy cows on the
      relationship between hindgut fermentation and N metabolism, and its effects on
      NH(3) absorption and transfer of blood urea-N across the portal-drained viscera
      versus ruminal epithelia were investigated. Nine lactating Holstein cows fitted
      with ruminal cannulas and permanent indwelling catheters in major splanchnic
      blood vessels were used in an unbalanced crossover design with 14-d periods.
      Treatments were continuous abomasal infusion of water or 1,500 g/d of
      oligofructose. The same basal diet was fed with both treatments. Eight sample
      sets of arterial, portal, hepatic, and ruminal vein blood, ruminal fluid, and
      urine were obtained at 0.5h before the morning feeding and at 0.5, 1.5, 2.5, 3.5,
      4.5, 5.5, and 6.5 h after feeding. It was hypothesized that an increased supply
      of fermentable substrate to the hindgut would increase the uptake of urea-N from
      blood to the hindgut at the expense of urea-N uptake to the forestomach. The
      study showed that abomasal oligofructose infusion decreased the total amount of
      urea-N transferred from the blood to the gut, NH(3) absorption, and arterial
      blood urea-N concentration. Subsequently, hepatic NH(3) uptake and urea-N
      production also decreased with oligofructose infusion. Additionally, urea-N
      concentration in milk and urinary N excretion decreased with oligofructose
      treatment. The oligofructose infusion did not affect ruminal NH(3) concentrations
      or any other ruminal variables, nor did it affect ruminal venous - arterial
      concentration differences for urea-N and NH(3). The oligofructose treatment did
      not affect milk yield, but did decrease apparent digestibility of OM, N, and
      starch. Nitrogen excreted in the feces was greater with the oligofructose
      infusion. In conclusion, the present data suggest that increased hindgut
      fermentation did not upregulate urea-N transfer to the hindgut at the expense of
      urea-N uptake by the rumen, and the observed reduction in arterial blood urea-N
      concentration appeared not to be due to increased urea-N transport, but rather
      could be explained by reduced NH(3) input to hepatic urea-N synthesis caused by
      increased sequestration of NH(3) in the hindgut and excretion in feces.
      Increasing the hindgut fermentation in lactating dairy cows by abomasal infusion
      of 1,500 g/d of oligofructose shifted some N excretion from the urine to feces
      and possibly reduced manure NH(3) volatilization without impairing rumen
      fermentation.

PMID- 22999278
TI  - Events occurring during the previous lactation, the dry period, and peripartum as
      risk factors for early lactation mastitis in cows receiving 2 different
      intramammary dry cow therapies.
AB  - The objective of this study was to investigate the association between mastitis
      events occurring during the previous lactation, the dry period, and the
      peripartum period on the incidence of early lactation mastitis in cows receiving
      ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow
      antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were
      enrolled in the study at the time of dry-off processing and were randomly
      assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin
      dihydrostreptomycin. Composite milk samples were collected at dry-off and after
      calving for bacteriological examination and somatic cell count. Peripartal health
      disorders were monitored during the first 30 d of lactation and included calving
      difficulty, metritis, ketosis, and left displaced abomasum. Milk production and
      individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd
      Improvement Association. The main outcome variables were the risk of clinical
      mastitis during the first 30 and 60 d of lactation, and the risk of subclinical
      mastitis at the first 2 monthly Dairy Herd Improvement Association tests after
      calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis
      pathogens in milk at dry-off and at calving were analyzed. Explanatory variables
      consisted of events occurring during the previous lactation, at dry-off and
      during the dry period, at calving, and within the first 30 d after calving.
      Multiple events occurring during the previous lactation had a significant effect
      on the incidence of mastitis in the subsequent lactation. These events included
      low milk yield, intermediate lactation length, clinical mastitis, and lactation
      SCS average. Similarly, intramammary infections with environmental bacteria at
      dry-off increased the chances of clinical mastitis the first month after calving.
      Dry-off therapy had a significant effect on mastitis incidence; cows treated with
      ceftiofur hydrochloride had lower odds of having clinical and subclinical
      mastitis in the subsequent early lactation compared with cows treated with
      penicillin dihydrostreptomycin.

PMID- 22999279
TI  - Technical note: Identification of Prototheca species from bovine milk samples by
      PCR-single strand conformation polymorphism.
AB  - We report the development of a PCR-single strand conformation polymorphism (SSCP)
      method to identify Prototheca spp. responsible for bovine mastitis: P. zopfii and
      P. blaschkeae. The method was set up using reference strains belonging to P.
      zopfii genotype 1, P. zopfii genotype 2, and P. blaschkeae as target species and
      P. stagnora, and P. ulmea as negative controls. The assay was applied on 50
      isolates of Prototheca spp. isolated from bovine mastitic milk or bulk-tank milk
      samples, and all isolates were identified as P. zopfii genotype 2. We conclude
      that the described PCR-SSCP approach is accurate, inexpensive, and highly
      suitable for the identification of P. zopfii genotype 2 on field isolates but
      also directly on milk, if preceded by a specific DNA extraction method.

PMID- 22999280
TI  - The trade network in the dairy industry and its implication for the spread of
      contamination.
AB  - In case of an outbreak of a foodborne disease, administrative decisions in the
      context of crisis management are only efficient if they follow standard practices
      and are specifically adapted to the outbreak situation in a timely manner. These
      goals are hard to achieve. The complexity of national and global trade structures
      obscures a clear view of trade flows and, consequently, it is often impossible to
      unravel complex trade links quickly. Furthermore, increasing public concerns
      about possible health hazards caused by global trade put additional pressure on
      decision makers. The aim of this paper was to unveil the specific trade
      structures of the German milk supply chain, to highlight how these structures
      could affect the spatial spread of a hypothetical contaminant, and to quantify
      the risk of the contaminant reaching the consumer. To achieve this goal, the
      vertical and horizontal trade links between milk producers, dairies, and
      consumers were taken into account. The horizontal flow of milk between dairies
      (inter-dairy trade), which is intended to compensate a temporary over- or
      undersupply of milk, is of special importance in this respect. We hypothesized
      that the extent of inter-dairy trade would significantly influence the spatial
      spread of contaminated milk and the contamination risk. This hypothesis was
      tested using a computer simulation model that predicts the hypothetical spread of
      a contaminant via trade of milk. The model parameters were estimated using trade
      data collected in 2004 and 2010. The results of our study indicate that inter
      dairy trade significantly influenced the contamination risk. Compared with a
      scenario with no inter-dairy trade, the risk that contaminated milk will reach
      the consumer was up to 4 times higher, even with moderate inter-dairy trade. The
      contamination risk depended on the extent of inter-dairy trade in a nonlinear way
      and reached its maximum asymptotically when inter-dairy trade increased. The
      contamination risk exhibited considerable spatial variation, which could be
      utilized to implement more accurate food control interventions in times of crisis
      caused by a foodborne disease.

PMID- 22999281
TI  - Viscoelasticity and texture of spreadable cheeses with different fat contents at
      refrigeration and room temperatures.
AB  - The effect of the 2 common consumption temperatures, refrigeration temperature
      (10 degrees C) and room temperature (22 degrees C), on the viscoelasticity,
      mechanical properties, and perceived texture of commercial cream cheeses was
      studied. Two samples with different fat contents, regular and low fat, from each
      of 4 selected commercial brands were analyzed. The selection criteria were based
      on identification of brands with different percentages of fat content reduction
      between the regular- and low-fat samples (35, 50, 84, and 98.5%). The fat content
      of regular-fat samples ranged from 19.8 to 26.0% (wt/wt), and that of low-fat
      samples ranged from 0.3 to 13.0% (wt/wt). Viscoelasticity was measured in a
      controlled-stress rheometer using parallel-plate geometry, and the mechanical
      characteristics of samples were measured using the spreadability test.
      Differences in the intensity of thickness, creaminess, and roughness between the
      regular- and low-fat samples of each commercial brand were evaluated at each of
      the selected temperatures by using the paired comparisons test. At 10 degrees C,
      all samples showed higher viscoelastic modulus values, firmness, and stickiness,
      and lower spreadability than when they were measured at 22 degrees C. Differences
      in viscoelasticity and mechanical properties between each pair of samples of the
      same brand were greater at 10 degrees C than at 22 degrees C because of the
      influence not only of fat content but also of fat state. Ingestion temperature
      did not modify the sensory differences detected between each pair of samples in
      terms of creaminess and roughness, but it did modify the differences detected in
      thickness. The joint consideration of sample composition, fat state, and product
      behavior during oral processing could explain the differences detected in
      thickness perceived because of measurement temperatures.

PMID- 22999282
TI  - Short communication: assessing urea transport from milk to blood in dairy cows.
AB  - The concentration of urea in milk (MUC) has emerged as a potentially useful tool
      to predict urinary N excretion. Various factors may affect the relationship
      between MUC and urinary N excretion, including transport characteristics of urea
      from blood to milk and vice versa. The main objective of this study was to test
      whether substantial transport of urea from milk to blood exists in lactating
      dairy cattle. The subobjectives were (1) to assess the effects of various urea
      gradient levels between blood and milk on urea transport from milk to blood and
      (2) to test the occurrence of urea transport between different compartments of
      the mammary gland such as the cistern and the alveoli. Urea transport was studied
      in 2 multiparous lactating Holstein-Friesian cows (36.0+/-6.18 kg of milk/d; mean
      +/- SD). In 3 separate trials, boluses of [(15)N(15)N]urea were injected in the
      cisterns via the teat canals at 20, 60, and 120 min before the 1700-h milking at
      various levels of MUC and of blood plasma urea concentration (PUC). In trial 1, a
      primed continuous infusion of urea (105 g at the start, continuing with 20 g/h)
      into the jugular vein started at 0500 h and stopped at 0, 1, 2, and 3h before the
      1700-h milking on d 1, 2, 3, and 4, respectively. In trial 2, 5.5 g of urea was
      injected into the cisterns at 20, 60, and 120 min before the 1700-h milking on d
      5, 6, and 7, respectively. In trial 3, urea fluxes were measured without an
      experimentally induced gradient between MUC and PUC on d 8, 9, and 10,
      respectively. During milking, successive milk samples were taken from first to
      last milk. Blood and milk were analyzed for (15)N-urea enrichment. Levels of
      (15)N-urea in blood increased after injection of a [(15)N(15)N]urea bolus in
      milk, indicating urea transport from milk to blood. Between 21.0 and 35.3% of
      injected [(15)N(15)N]urea in milk was recovered after 2 h. The fractional
      [(15)N(15)N]urea decline rate in milk varied between 0.0076 and 0.0096/min. The
      level of MUC, rather than the concentration gradient between MUC and PUC,
      appeared to affect this fractional rate of decline. Enrichment levels of (15)N
      urea in milk samples within a single milking showed that urea was transported
      from cistern milk to alveoli milk. In conclusion, the results indicate that
      transport of urea from milk to blood in lactating dairy cattle occurs and that
      urea is transported from cistern milk to alveoli milk.

PMID- 22999283
TI  - Genetic relationship of conformation traits with average somatic cell score at
      150 and 305 days in milk in Holstein cows of Iran.
AB  - Genetic, environmental, and phenotypic correlations among average somatic cell
      score (SCS) at different stages of lactation and conformation traits were
      estimated. Data consisted of the lactational average of SCS at 150 (SCS(150)) and
      305 (SCS(305)) d in milk and 19 conformation traits recorded on 57,154
      primiparous Holstein cows, that calved from 1996 to 2009 in 119 herds in Iran.
      Variance components were estimated using the restricted maximum likelihood
      procedure based on multiple-trait animal models. Udder depth (-0.32), fore udder
      attachment (-0.22), and udder width (0.34) showed moderate genetic correlation
      with SCS(150). Heart girth (0.17), body depth (0.14), chest width (0.26), and
      angularity (0.19), showed modest genetic correlation with SCS(150). The estimated
      heritabilities for SCS(150) and SCS(305) were 0.06 and 0.08, respectively. The
      heritability of the conformation traits ranged from 0.09 to 0.29. Genetic and
      environmental correlations between SCS(150) and SCS(305) were very high (means +/
      SE; 0.99+/-0.01 and 0.89+/-0.01, respectively), which indicates that recording
      SCS over a shorter period of lactation is an alternative approach for involving
      many herds in SCS data collection. The low heritability of SCS indicated that
      indirect selection for some of udder and body traits might be helpful to reduce
      the SCS. Additionally, selection for udder traits may help reduce SCS in
      developing countries where SCS data are sparsely recorded.

PMID- 22999284
TI  - The evolution of productivity performance on China's dairy farms in the new
      millennium.
AB  - China's dairy farm structure has experienced fundamental changes across farm
      types. As the number of backyard farms has dramatically declined, the share of
      dairy cows from backyard farms has decreased by 22.4% from 2003 to 2008. However,
      the herd numbers of larger dairy farms have increased. In particular, the share
      of dairy cows has risen by 18.8% on small farms, by 22.2% on medium farms, and by
      80.8% on large farms over the same period. Total factor productivity was
      decomposed into technical efficiency and technological change on China's dairy
      farms using the stochastic production frontier framework. The estimated results
      indicate that patterns of productivity growth appear to have shifted in the 2000s
      compared with the 1990s, from generally driven by technological change to
      exclusively driven by technological change on backyard and small farms and
      uniquely driven by the improvement of technical efficiency on large farms. Tests
      of the econometric assumption indicate that the variations in total factor
      productivity growth patterns across farm types and regions are likely caused by
      the feed input biases and cropping production practice.

PMID- 22999285
TI  - Characterization of coagulase-negative staphylococcus species from cows' milk and
      environment based on bap, icaA, and mecA genes and phenotypic susceptibility to
      antimicrobials and teat dips.
AB  - The aim of this study was to investigate whether the main coagulase-negative
      staphylococci (CNS) species involved in bovine intramammary infections (IMI)
      possess specific characteristics that promote colonization of the udder.
      Virulence markers associated with biofilm formation, antimicrobial resistance,
      and biocide tolerance were compared between typically contagious CNS species
      (Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus
      haemolyticus, and Staphylococcus simulans) and those rarely causing IMI
      (Staphylococcus sciuri, Staphylococcus equorum, and others) to find possible
      associations with pathogenicity. Coagulase-negative staphylococci isolates
      (n=366) belonging to 22 different species were analyzed by PCR for the presence
      of the biofilm-associated genes bap and icaA, and the methicillin resistance gene
      mecA. A selection of 82 isolates was additionally tested for their susceptibility
      to 5 antibiotics and 2 commercial teat dip products. Minimum inhibitory
      concentrations of antimicrobials were determined by Etest (AB bioMerieux, Marcy
      l'Etoile, France), and a microdilution method was optimized to determine minimum
      biocidal concentrations of teat dips. The bap, icaA, and mecA genes were detected
      significantly more in isolates from CNS species typically living in the cows'
      environment than in isolates from IMI-causing species. Antimicrobial resistance
      was mainly against erythromycin (23%) or oxacillin (16%), and was detected more
      often in the environmental species. The isolates least susceptible to the teat
      dips belonged to the IMI-causing species Staph. chromogenes and Staph. simulans.
      We concluded that carriage of biofilm genes and antimicrobial resistance were not
      associated with the ability to colonize the mammary gland because free-living CNS
      species constituted a more significant reservoir of biofilm and resistance
      determinants than did IMI-causing species. In contrast, increased tolerance to
      biocides may favor the establishment of bovine IMI by some CNS species.

PMID- 22999286
TI  - Short communication: Streptococcus species isolated from mastitis milk samples in
      Germany and their resistance to antimicrobial agents.
AB  - Mastitis is one of the most frequent infectious diseases in dairy cattle and is a
      reason for antimicrobial drug usage in dairy cows. The bacteria involved in
      bovine mastitis are mainly Streptococcus spp., Staphylococcus spp., and
      coliforms. The aim of this study was to determine antimicrobial resistance among
      Streptococcus spp. isolated from bovine mastitis milk. Antimicrobial resistance
      in Strep. uberis (n=227), Strep. dysgalactiae (n=49), and Strep. agalactiae (n=3)
      was determined for 9 antimicrobial agents using the broth microdilution method in
      accordance with Clinical and Laboratory Standards Institute recommendations. Of
      all Streptococcus spp., 13% were multidrug resistant. The rate of multidrug
      resistance was higher among Strep. uberis (15%) than among Strep. dysgalactiae
      (6%) and Strep. agalactiae (0%). Resistance to tetracycline was the most common,
      followed by resistance to erythromycin, pirlimycin, and gentamicin. Resistance
      rates were higher on farms with more than 80 cows compared with those with fewer
      than 20 cows. beta-Lactams should remain the drugs of choice in the treatment of
      streptococcal mastitis. The slightly elevated minimum inhibitory concentrations
      determined for these antibiotics may indicate, however, the emergence of
      resistant streptococci. To identify such changes in susceptibility as early as
      possible, antimicrobial resistance in streptococci should be surveyed regularly.

PMID- 22999287
TI  - Short communication: Characterization of Shiga toxin 2-carrying bacteriophages
      induced from Shiga-toxigenic Escherichia coli isolated from Italian dairy
      products.
AB  - Forty samples of raw milk cheese and 25 samples of raw milk itself were subjected
      to enrichment culture for Shiga-toxigenic Escherichia coli (STEC), and a single
      Shiga toxin 2- (Stx(2)) positive strain was obtained from one of the cheese
      samples. Thus, aged cheeses in which the curd is subsequently heat treated (48
      degrees C) cannot be presumed to be STEC free. Infective Stx(2) bacteriophages
      were induced from 3 STEC strains isolated elsewhere from raw milk and 1 STEC
      strain from aged cheese sourced in Italy. Data on E. coli host range, morphology,
      genome size, and genetic variation determined by restriction fragment length
      polymorphism and multi-locus genotyping are presented. Although all 4
      bacteriophages were found to be short-tailed Podoviridae, they exhibited
      considerable variation in both genome size and content. This extended to the
      Stx(2) genes themselves, whose sequences contained several point mutations, but
      these did not translate to amino acid substitutions.

PMID- 22999288
TI  - Short communication: Glutamine increases autophagy of liver cells in weaned
      calves.
AB  - The objectives of this study were to determine the effects of an increased
      jugular supply of l-Gln on the autophagy of weaned calves. At 35 d of age, 24
      Holstein calves (initial body weight of 50+/-0.5 kg; 35+/-2 d of age) were
      randomly allocated to 4 treatments, with each treatment including 5 male calves
      and 1 female calf. Holstein calves were assigned to treatments of (1) intravenous
      infusion of 2d of 0.85% NaCl (control group) (2) intravenous infusion of 8 g/d of
      L-Gln mixed with 2d of 0.85% NaCl solution, (3) intravenous infusion of 16 g/d of
      L-Gln mixed with 2d of 0.85% NaCl solution, and (4) intravenous infusion of 32
      g/d of L-Gln mixed with 2d of 0.85% NaCl. The infusion was administered 2h/d for
      7 consecutive days starting on d 1 after weaning. Feed and water were freely
      available to all calves. All calves were killed on d 7 postweaning to measure the
      autophagy of liver cells. The level of autophagy in liver cells was improved when
      the Gln infusion dose increased.

PMID- 22999289
TI  - The influence of feed and herd on fatty acid composition in 3 dairy breeds
      (Danish Holstein, Danish Jersey, and Swedish Red).
AB  - The composition of milk fat from dairy cows is related to both genetic and
      environmental factors. Here, the effect of feed and herd was examined in 3
      Scandinavian breeds, namely Danish Holstein-Friesian (DH), Danish Jersey (DJ),
      and Swedish Red (SR). In total, milk samples from 1,298 cows kept in indoor
      housing systems were collected from 61 conventional dairy herds in Denmark and
      Sweden. The fatty acid (FA) composition of milk was determined by gas
      chromatography and the content of alpha-tocopherol by HPLC. Based on the 17
      individual FA determined, distinct FA profiles were observed for all breeds using
      univariate and multivariate statistics. The DJ cows were characterized by higher
      levels of saturated short-chain FA; in contrast, DH cows had higher content of
      unsaturated C18 FA, whereas higher levels of primarily C14:0, C14:1, C18:1 cis-9,
      and C18:3n-3 were evident in SR cows. This variation in milk fat composition
      across breeds was further reflected in different desaturase indices, which were
      generally higher in SR cows. In addition, alpha-tocopherol differed significantly
      among breeds, with DJ cows having the highest content. Herd-specific feeding
      plans were collected, and different feed items were separated into 4 broad feed
      categories, including grass products, maize silage, grain, and concentrate. The
      pronounced differences in overall feed composition among breeds were, to a large
      extent, due to regional differences between countries, with SR receiving higher
      levels of grain and grass silage compared with the Danish breeds. Within breeds,
      differences in feeding regimens among herds were furthermore higher in SR.
      Significant correlations between feed category and individual FA were observed in
      all breeds. Furthermore, variance components were estimated and used to determine
      the proportion of phenotypic variation that could be explained by herd. The herd
      effect for individual FA was generally lower for DH compared with the 2 other
      breeds. In addition, very low herd effects were shown for C14:1 and C16:1 in all
      breeds, suggesting that the content of these FA is mainly genetically regulated.

PMID- 22999290
TI  - Comparison between mechanical and near-infrared methods for assessing coagulation
      properties of bovine milk.
AB  - The aim of the present study was to compare milk coagulation properties measured
      through a traditional mechanical device, the Formagraph (FRM; Foss Electric A/S,
      Hillerod, Denmark), and a near-infrared optical device, the Optigraph (OPT;
      Ysebaert SA, Frepillon, France). Individual milk samples of 913 Brown Swiss cows
      from 63 herds located in Trento Province (Italy) were analyzed for rennet
      coagulation time (RCT, min), curd-firming time (k(20), min), and 2 measures of
      curd firmness (a(30) and a(45),mm) using the 2 instruments and under identical
      conditions. The trial was performed in the same laboratory, by the same
      technician, and following the same procedures. Extending the analysis by either
      instrument to 90 min permitted RCT and k(20) values to be obtained even for late
      coagulating milk samples. Milk coagulation properties measured using the OPT
      differed considerably from those obtained using the FRM. The average k(20) values
      varied greatly (8.16 vs. 5.36 min for the OPT and the FRM, respectively), as did
      the a(45) figures (41.49 vs. 33.66 mm for the OPT and the FRM, respectively). The
      proportion of noncoagulating samples for which k(20) could be estimated differed
      between instruments, being less for the OPT. The between-instrument correlation
      coefficients were either moderate (0.48 for a(30)) or low (0.24 and 0.17 for
      k(20) and a(45), respectively) when the same traits were compared. The
      correlations between k(20) and a(45), and milk yield varied among instruments, as
      did the correlations between k(20), a(30), and a(45) and milk composition, and
      the correlations between a(45) and pH. The relative influence of days in milk on
      k(20) and a(45) varied, as did the effect of parity on a(45) and that of the
      measuring unit of coagulation meter on k(20) and a(30). The RCT estimated by the
      OPT was the only milk coagulation property to show good agreement with the FRM
      derived value, although this was not true for the data from late-coagulating
      samples.

PMID- 22999291
TI  - Rapeseed or linseed in grass-based diets: effects on conjugated linoleic and
      conjugated linolenic acid isomers in milk fat from Holstein cows over 2
      consecutive lactations.
AB  - Changes in the distribution of conjugated linoleic (CLA) and conjugated linolenic
      (CLnA) acid isomers in milk from Holstein cows in response to 4 different oilseed
      supplements rich in either cis-9 18:1 or 18:3n-3 were determined over 2
      consecutive lactations in 58 and 35 cows during the first and second years,
      respectively. For the first 5 wk of the first lactation, all cows were fed the
      same diet. Thereafter, cows received 1 of 5 treatments for 2 consecutive
      lactations, including the prepartum period. Treatments comprised the basal diet
      with no additional lipid, or supplements of extruded linseeds (EL), extruded
      rapeseeds (ER), cold-pressed fat-rich rapeseed meal, or whole unprocessed
      rapeseeds to provide 2.5 to 3.0% of additional oil in diet dry matter. During
      indoor periods, cows were housed and received a mixture (3:1, wt/wt) of grass
      silage and hay, whereas cows were at pasture during outdoor periods. Over the
      entire study, EL resulted in the enrichment of ?11,13 CLA, ?12,14 CLA, trans
      9,trans-11 CLA, trans-13,trans-15 CLA, ?9,11,15 CLnA, and cis-9,trans-11,trans-13
      CLnA (identified for the first time in bovine milk fat) in milk fat, whereas ER
      and cold-pressed fat-rich rapeseed meal in particular, increased milk fat trans
      7,cis-9 CLA concentration. With the exception of the first indoor period, whole
      unprocessed rapeseeds decreased cis-9,trans-11 CLA, trans-9,cis-11 CLA, and trans
      10,trans-12 CLA abundance. During the second indoor period, EL increased milk
      trans-9,cis-11 CLA and trans-10,cis-12 CLA concentrations, but the increases in
      cis-9,trans-11 CLA, cis-12,trans-14 CLA, trans-11,cis-13 CLA, and cis-9,trans
      11,cis-15 CLnA concentrations to EL and ER were lower for the second than first
      indoor period. In contrast to the indoor periods, EL and ER decreased milk cis
      9,trans-11 CLA, trans-9,cis-11 CLA, and trans-10,cis-12 CLA concentrations at
      pasture. The extent of changes in the relative distribution and abundance of CLA
      and CLnA isomers in milk fat were related to the nature (rapeseed or linseed) and
      form of oilseed (extruded, cold-pressed fat-rich meal or whole unprocessed)
      supplement and their interactions with the composition of the basal diet
      (conserved grass or pasture and dietary starch content). Furthermore, milk fat
      CLA and CLnA responses to treatments were repeatable between both outdoor
      periods. Variations in milk fat content and yield measured during the entire
      study were significantly and inversely associated with milk trans-10 18:1, trans
      10,cis-12 CLA, and in particular, trans-9,cis-11 CLA concentrations.

PMID- 22999292
TI  - Memantine as adjunctive treatment to risperidone in children with autistic
      disorder: a randomized, double-blind, placebo-controlled trial.
AB  - Autism is a neurodevelopmental disorder that causes significant impairment in
      socialization and communication. It is also associated with ritualistic and
      stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic
      ideologies for autism. The objective of this study was to assess the effects of
      memantine plus risperidone in the treatment of children with autism. Children
      with autism were randomly allocated to risperidone plus memantine or placebo plus
      risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of
      risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d.
      Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting
      medication protocol. The primary outcome measure was the irritability subscale of
      Aberrant Behavior Checklist-Community (ABC-C). Difference between the two
      treatment arms was significant as the group that received memantine had greater
      reduction in ABC-C subscale scores for irritability, stereotypic behaviour and
      hyperactivity. Eight side-effects were observed over the trial, out of the 25
      side-effects that the checklist included. The difference between the two groups
      in the frequency of side-effects was not significant. The present study suggests
      that memantine may be a potential adjunctive treatment strategy for autism and it
      was generally well tolerated. This trial is registered with the Iranian Clinical
      Trials Registry (IRCT1138901151556N10; www.irct.ir).

PMID- 22999293
TI  - Significance of handling, formulation and storage conditions on the stability and
      bioactivity of rhBMP-2.

PMID- 22999294
TI  - Fulvestrant treatment of precocious puberty in girls with McCune-Albright
      syndrome.
AB  - BACKGROUND: McCune-Albright Syndrome (MAS) is usually characterized by the triad
      of precocious puberty (PP), fibrous dysplasia, and cafe au lait spots. Previous
      treatments investigated for PP have included aromatase inhibitors and the
      estrogen receptor modulator, tamoxifen. Although some agents have been partially
      effective, the optimal pharmacologic treatment of PP in girls with MAS has not
      been identified. The objective of this study was to evaluate the safety and
      efficacy of fulvestrant (FaslodexTM), a pure estrogen receptor antagonist, in
      girls with progressive precocious puberty (PP) associated with McCune-Albright
      Syndrome (MAS). METHODS: In this prospective international multicenter trial,
      thirty girls <= 10 years old with MAS and progressive  PP received fulvestrant 4
      mg/kg via monthly intramuscular injections for 12 months. Changes in vaginal
      bleeding, rates of bone age advancement, growth velocity, Tanner staging,
      predicted adult heights, and uterine and ovarian volumes were measured. RESULTS:
      Median vaginal bleeding days decreased from 12.0 days per year to 1.0 day per
      year, with a median change in frequency of -3.6 days, (95% confidence interval
      (CI) -10.10, 0.00; p = 0.0146). Of patients with baseline bleeding, 74%
      experienced a >=50% reduction in bleeding, and 35% experienced complete cessation
      during the study period (95% CI 51.6%, 89.8%; 16.4%, 57.3%, respectively).
      Average rates of bone age advancement (DeltaBA/DeltaCA) decreased from 1.99 pre
      treatment to 1.06 on treatment (mean change -0.93, 95% CI -1.43, -0.43; p =
      0.0007). No significant changes in uterine volumes or other endpoints or serious
      adverse events occurred. CONCLUSIONS: Fulvestrant was well tolerated and
      moderately effective in decreasing vaginal bleeding and rates of skeletal
      maturation in girls with MAS. Longer-term studies aimed at further defining
      potential benefits and risks of this novel therapeutic approach in girls with MAS
      are needed. TRIAL REGISTRATION: NCT00278915.

PMID- 22999295
TI  - Next-generation personalized drug discovery: the tripeptide GHK hits center stage
      in chronic obstructive pulmonary disease.
AB  - Chronic lung diseases (CLDs), including chronic obstructive pulmonary disease
      (COPD), are the second leading cause of death worldwide. The first report of
      database-driven drug discovery in carefully phenotyped COPD specimens has now
      been published in Genome Medicine, combining gene expression data in defined
      emphysematous areas with connectivity-map-based compound discovery. This joint
      effort may lead the way to novel and potentially more efficient concepts of
      personalized drug discovery for COPD in particular, and CLD in general. See
      research article http://genomemedicine.com/content/4/8/67/abstract. 

PMID- 22999296
TI  - Osteonecrosis of the jaw onset times are based on the route of bisphosphonate
      therapy.
AB  - PURPOSE: Osteonecrosis of the jaw (ONJ) has been reported to be associated with
      patients receiving bisphosphonate (BP) therapy. There are many reports that
      suggest that the time of exposure to BPs is a significant risk factor for ONJ and
      that the greatest risk occurs after dentoalveolar surgery. The aim of this study
      was to retrospectively investigate the duration of BP therapy and related events
      before the onset of ONJ based on an intravenous (IV) or oral route of
      administration. MATERIALS AND METHODS: We conducted a retrospective cohort study
      of patients referred to our institution to identify the onset of ONJ based on the
      exposure to BP therapy and associated triggers (ie, dentoalveolar surgery or
      spontaneous occurrence) based on the route of BP administration. Demographic data
      (ie, age, gender, and race), medical diagnosis related to BP therapy, and
      information as to whether the BP therapy was continued at the time of ONJ
      diagnosis were also collected. RESULTS: We reviewed the records for 114 patients
      with a history of ONJ. We divided patient cohorts by route of BP administration,
      with 76 patients having a history of IV BP therapy and 38 patients having a
      history of oral BP therapy. The overall onset of ONJ was earlier in the IV BP
      group (median, 3 years) compared with the oral BP group (median, 5 years). There
      was no statistical difference in the duration to occurrence of ONJ associated
      with dental extraction compared with spontaneous occurrence for both the IV and
      oral BP groups. CONCLUSIONS: The median onset of ONJ for patients undergoing IV
      BP therapy occurs earlier than the median onset for patients undergoing oral BP
      therapy, and there was no difference in onset occurring spontaneously and after
      dental extraction. The significance of these findings suggests that patients who
      receive IV BP therapy should be closely evaluated after the initiation of BP
      therapy. The lack of evidence suggesting greater onset after dental extraction
      may provide clinical support for dentoalveolar surgery that is indicated for
      patients with a history of BP therapy. Research focusing on the clinical
      circumstances and physiologic events during early antiresorptive therapy may
      provide insight as to the critical risk factors.

PMID- 22999297
TI  - Preoperative planning and intraoperative technique for accurate realignment of
      the Dwyer calcaneal osteotomy.
AB  - The Dwyer calcaneal osteotomy is an effective procedure for the correction of
      calcaneal varus deformity. However, no intraoperative method has been described
      to determine the amount of bone resection. We describe a simple intraoperative
      method for assuring accurate bone resection and measure the realignment effects
      of the Dwyer calcaneal osteotomy. We also review radiographic outcomes associated
      with 20 Dwyer calcaneal osteotomies (in 17 patients) using the intraoperative
      realignment technique described in this report. Preoperative and postoperative
      radiographs at a mean of 2.5 (range 1.5 to 5) years taken after Dwyer osteotomy
      were measured and compared, which revealed a mean reduction in calcaneal varus of
      18 degrees  (range 2 degrees  to 36 degrees ) (p < .001), a mean decrease in the
      calcaneal inclination angle of 5 degrees  (range -40 degrees  to 7 degrees ) (p <
      .05), a mean decrease in medial calcaneal translation of 10 (range 0 to 18) mm (p
      < .001) relative to the tibia, and a mean dorsal translation of 2 (range 0 to 7)
      mm (p = .002). In an effort to attempt to structurally realign the calcaneus to a
      more rectus alignment, by means of Dwyer osteotomy, we recommend the use of the
      intraoperative bone wedge resection technique described in this report. Our
      experience with the patients described in this report demonstrates the usefulness
      of the intraoperative method that we describe in order to accurately restore the
      axial tibial and calcaneal relationship.

PMID- 22999298
TI  - Is the difference in neonatal blood glucose concentration of caesarian and
      vaginally delivered term infants requiring separated reference intervals?
AB  - BACKGROUND: Mode of delivery has been reported to affect the cord blood glucose
      level of newborns. Vaginally delivered (VD) newborns were found to have
      relatively increased concentration of cord blood glucose than those delivered by
      cesarean section (CS). The aim of this study is thus to determine whether the
      difference in cord blood glucose concentration among VD and CS newborns is
      necessitating partitioned reference intervals (RIs) for the laboratory diagnosis
      of neonatal hypoglycemia. METHODS: A total of 60 newborns were included from
      Tikur Anbessa Specialized Hospital (TASH). Cord blood samples were collected and
      analyzed for glucose by Glucose-oxidase (GOD-PAP) method in TASH laboratory using
      HumaStar 300 from November 2010 to April 2011. All pre-analytical, analytical and
      post-analytical aspects were thoroughly controlled. A robust method was used for
      the determination of reference intervals using MedCalc(r) software Version
      11.6.1. RESULTS: VD newborns accounted for 71.7% (n = 43) while the CS newborns
      accounted for 28.3% (n = 17). No statistically significant difference was noted
      in the studied demographic variables among VD and CS newborns except for blood
      glucose level. The RIs were then determined to be 2.46-6.85 mmol/l and 2.46-5.04
      mmol/l for VD and CS newborns respectively. The combined RI was 2.24-6.48 mmol/l.
      CONCLUSION: Combined RI better be used for the interpretation of cord blood
      glucose values in VD and CS newborns. Cord blood glucose concentrations of 2.24
      mmol/l can be used as statistical estimates of cut off points for neonatal
      hypoglycemia in newborns irrespective of their mode of deliveries.

PMID- 22999300
TI  - Collaborative practice in the PICU: the Nurse Practitioner role complementing
      delivery of care [corrected].

PMID- 22999301
TI  - A rapid profiling of gallotannins and flavonoids of the aqueous extract of Rhus
      coriaria L. by flow injection analysis with high-resolution mass spectrometry
      assisted with database searching.
AB  - Hydrolysable tannins appear to have some extremely important biological roles
      including antioxidant, antibacterial, anti-inflammatory, anti-hypoglycemic, anti
      angiogenic, and anticancer activities. The aim of this work was to set up a flow
      injection high-resolution mass spectrometric approach combined with database
      searching to obtain rapidly a profiling of gallotannins and other phenolics in a
      crude extract from plant tissue. The flow injection analysis (FIA) takes place in
      an electrospray ionization source of an hybrid orbitrap high resolution mass
      spectrometry system (ESI-HR-MS/MS(2), resolution 100,000, negative ion mode) and
      polyphenols are tentatively identified by matching the monoisotopic masses of the
      spectra with those of polyphenols databases. This leads to the most probable
      molecular formulas and to the possible structures among those reported in the
      database. The structures confirmation occurs by the compliance of MS(2) fragments
      with those of a prediction fragment commercial database. With this method we
      identified in the aqueous extract of sumac leaves, with a maximum error of 1.7
      ppm, a group of ten gallotannins from mono- to deca-galloyl glycosides of the
      class of hydrolysable tannins and a set of coextracted flavonoid derivatives
      including myricetin, quercetin-3-O-rhamnoside, myricetin-3-O-glucoside, myricetin
      3-O-glucuronide, and myricetin-3-O-rhamnoglucoside. The separation of isomers of
      gallotannins and flavonoids present in the same extract occurred by high
      performance liquid chromatography with electrospray ionization tandem mass
      spectrometry (HPLC/ESI-HR-MS(2)); this approach allowed the structure resolution
      of the isobaric flavonoids quercetin-3-O-glucoside and myricetin-3-O-rhamnoside.

PMID- 22999299
TI  - The DeltaF508-CFTR mutation inhibits wild-type CFTR processing and function when
      co-expressed in human airway epithelia and in mouse nasal mucosa.
AB  - BACKGROUND: Rescue or correction of CFTR function in native epithelia is the
      ultimate goal of CF therapeutics development. Wild-type (WT) CFTR introduction
      and replacement is also of particular interest. Such therapies may be complicated
      by possible CFTR self-assembly into an oligomer or multimer. RESULTS:
      Surprisingly, functional CFTR assays in native airway epithelia showed that the
      most common CFTR mutant, DeltaF508-CFTR (DeltaF-CFTR), inhibits WT-CFTR when both
      forms are co-expressed. To examine more mechanistically, both forms of CFTR were
      transfected transiently in varying amounts into IB3-1 CF human airway epithelial
      cells and HEK-293 human embryonic kidney cells null for endogenous CFTR protein
      expression. Increasing amounts of DeltaF-CFTR inhibited WT-CFTR protein
      processing and function in CF human airway epithelial cells but not in
      heterologous HEK-293 cells. Stably expressed DeltaF-CFTR in clones of the non-CF
      human airway epithelial cell line, CALU-3, also showed reduction in cAMP
      stimulated anion secretion and in WT-CFTR processing. An ultimate test of this
      dominant negative-like effect of DeltaF-CFTR on WT-CFTR was the parallel study of
      two different CF mouse models: the DeltaF-CFTR mouse and the bitransgenic CFTR
      mouse corrected in the gut but null in the lung and airways. WT/DeltaF
      heterozygotes had an intermediate phenotype with regard to CFTR agonist responses
      in in vivo nasal potential difference (NPD) recordings and in Ussing chamber
      recordings of short-circuit current (ISC) in vitro on primary tracheal epithelial
      cells isolated from the same mice. In contrast, CFTR bitransgenic +/-
      heterozygotes had no difference in their responses versus +/+ wild-type mice.
      CONCLUSIONS: Taken altogether, these data suggest that DeltaF-CFTR and WT-CFTR co
      assemble into an oligomeric macromolecular complex in native epithelia and share
      protein processing machinery and regulation at the level of the endoplasmic
      reticulum (ER). As a consequence, DeltaF-CFTR slows WT-CFTR protein processing
      and limits its expression and function in the apical membrane of native airway
      epithelia. Implications of these data for the relative health of CF heterozygous
      carriers, for CFTR protein processing in native airway epithelia, and for the
      relative efficacy of different CF therapeutic approaches is significant and is
      discussed.

PMID- 22999302
TI  - ESI-MSn and LC-ESI-MS studies to characterize forced degradation products of
      bosentan and a validated stability-indicating LC-UV method.
AB  - The present study reports the characterization of forced degradation products of
      bosentan and a validated stability-indicating HPLC method for the stability
      testing of bosentan tablets. The forced degradation was carried out under the
      conditions of hydrolysis, oxidation, dry heat and photolysis. The drug was found
      unstable in acid, alkali and oxidative media whereas stable to the hydrolysis in
      water, to dry heat and to photolysis. In total, six degradation products were
      formed in all conditions which were resolved in a single run on a C-18 column
      with gradient elution using ammonium acetate buffer (pH 4.5, 5.0mM), methanol and
      acetonitrile. Structures of all the degradation products were characterized
      through +ESI-MS(n) and LC-ESI-MS spectral data of bosentan as well as LC-ESI-MS
      spectral data of the products. The products II-VI were characterized as 6-amino
      [2,2']bipyrimidinyl-4,5-diol, 6-amino-5-(2-methoxyphenoxy)-[2,2']-bipyrimidinyl-4
      ol, 2-[6-amino-5-(2-methoxyphenoxy)-[2,2']-bipyrimidinyl-4-yloxy]-ethanol, 4-tert
      butyl-N-[6-(1-methoxyethoxy)-5-(2-methoxyphenoxy)-[2,2']-bipyrimidinyl-4-yl]
      benzenesulfonamide and 4-tert-butyl-N-[6-hydroxy-5-(2-methoxyphenoxy)
      [2,2']bipyrimidinyl-4-yl]-benzenesulfonamide, respectively. The peak of the
      product I was found to be due to two secondary degradation products which co
      eluted and were characterized as beta-hydroxyethyl p-tert-butylphenylsulfonate
      (Ia) and 2-[2-(2-hydroxyethoxy)-phenoxy]-ethanol (Ib). These products were formed
      due to hydrolysis of sulfonamide and alkylaryl ether and the diaryl ether
      linkages as well as dehydration of the primary alcohol group. The most probable
      degradation mechanisms were proposed. The HPLC method was found to be stability
      indicating, linear (2-100 MUg ml(-1)), accurate, precise, sensitive, specific,
      rugged and robust for quantitation of the drug. The method was applied to the
      stability testing of the commercially available bosentan tablets successfully.

PMID- 22999303
TI  - Mycobacterium bovis infections in slaughter pigs in Mubende district, Uganda: a
      public health concern.
AB  - BACKGROUND: Bovine tuberculosis (TB) caused by Mycobacterium bovis is primarily a
      disease of ruminants, particularly cattle (Bos primigenius) and buffalo (Syncerus
      caffer), and is endemic in most developing countries. To date, studies done in
      Uganda have documented the prevalence of M. bovis in cattle, humans and wild
      life, in addition to non-tuberculous mycobacteria in pigs. Pigs are increasingly
      becoming an important component of the livestock sector and share the human
      ecosystem in rural Uganda. It is therefore of public health interest that they
      are not a source of human infections. As a follow up to previously published
      findings on mycobacteria in pigs, this study was aimed at investigating the
      occurrence and molecular characteristics of M. bovis detected in slaughter pigs
      in Mubende district, Uganda. One hundred fifty mesenteric lymph nodes with
      lesions suggestive of mycobacterial infections were collected from approximately
      one thousand slaughtered pigs in Mubende district over a period of five months.
      The isolation and identification of M. bovis was done using conventional
      mycobacteriological methods. Mycobacteria belonging to the Mycobacterium
      tuberculosis complex (MTC) were identified to species level using deletion
      analysis. Molecular typing was done using Spoligotyping and MIRU-VNTR analysis.
      Molecular data were analysed and interpreted using MIRU-VNTR plus, SpolDB4.0 and
      the Mycobacterium bovis spoligo database. RESULTS: Of the examined animals, one
      boar and two sows from Madudu Sub County were infected with M. bovis which
      presented as lesions of a deep yellow colour and a grit-like texture in the
      mesenteric lymph nodes. This represents 2% (3/150) of the lymph nodes where
      lesions suggestive of mycobacterial infections were detected. Molecular analysis
      revealed that the isolates from the infected pigs showed identical MIRU-VNTR
      profile and spoligotype (SB1469). CONCLUSIONS: This is the first study
      documenting the occurrence of M. bovis in slaughter pigs in Uganda, revealing
      that one in fifty slaughter pigs with suspected lesions in mesenteric lymph nodes
      were infected. Molecular analysis revealed that the isolates were identical,
      showing a spoligotype previously reported from humans and cattle in the north
      eastern part of the Uganda cattle corridor. This finding is of public health
      importance, therefore there is a need for close cooperation between medical and
      veterinary professionals in designing and implementing control and prevention
      measures that safeguard the public from this potential source of zoonotic TB in
      Uganda.

PMID- 22999304
TI  - Phosphorus fluxes at the sediment-water interface in subtropical wetlands
      subjected to experimental warming: a microcosm study.
AB  - Global warming is increasingly challenging for wetland ecological function. A
      temperature controlled microcosm system was developed to simulate climate change
      scenarios of an ambient temperature (control) and an elevated temperature (+5 
      degrees C). The effects and associated mechanisms of warming on phosphorus (P)
      fluxes at the sediment-water interface of six subtropical wetlands were
      investigated. The results indicated that P fluxes were generally enhanced under
      the experimental warming as measured by higher P concentrations in the porewater
      and overlying water as well as higher benthic P fluxes. The release of P from
      sediment to porewater occurred more strongly and quickly in response to
      experimental warming compared to the subsequent upward transfer into overlying
      water. The average accumulative benthic P output from the tested wetlands under
      the experimental warming was greater by 12.9 MUg cm(-2) y(-1) (28%) for total P
      and 8.26 MUg cm(-2) y(-1) (25%) for dissolved reactive P, compared to the ambient
      scenarios. Under warming the redistribution of P fractions in sediments occurred
      with greater NH(4)Cl-P and lower BD-P (extracted by a bicarbonate buffered
      dithionite solution) accompanied by greater NaOH-P. The higher temperature
      enhanced total phospholipid fatty acids. A shift in the microbial community was
      also observed with a relative dominance of fungi (a 4.7% increase) and a relative
      decline (by 18%) in bacterial abundance, leading to the higher secretion of
      phosphatase. Comparing between wetlands, the potential P fluxes in the nutrient
      enriched wetlands were less impacted by warming than the other wetland types
      investigated. Thus wetlands characterized by low or medium concentrations of P in
      sediments were more susceptible to warming compared to P-rich wetlands.

PMID- 22999305
TI  - A short measure of quality of life in older age: the performance of the brief
      Older People's Quality of Life questionnaire (OPQOL-brief).
AB  - Promoting quality of life in older age is an internationally recognized priority,
      requiring valid measurement. We present a short version of the established Older
      People's Quality of Life questionnaire (OPQOL-brief). The full OPQOL-35 was
      original in being developed from the perspectives of older people, assessed
      conceptually, and validated with a population sample using gold-standard
      psychometric assessment. The OPQOL-brief was also developed by asking older
      people to prioritize the most important items from the OPQOL-35, next assessed
      psychometrically with a population sample, and also statistically against the
      discarded 22 items. The aim was to assess the psychometric properties of the
      short, 13-item version of the OPQOL (OPQOL-brief), and to compare the performance
      of included and discarded items. The method was a national population survey of
      people aged 65+ living at home. The measures were OPQOL-brief, WHOQOL-QOL and
      CASP-19. The OPQOL-brief was found to be a highly reliable and valid, short
      measure of quality of life in older age. The OPQOL-brief is of value in
      assessment of interventions where a rigorously tested, short measure is required.
      The grounded development of the instrument is consistent with international
      policy emphasis on user involvement in shaping policy and research.

PMID- 22999306
TI  - Prevalence and predictors of falls and dizziness in people younger and older than
      80 years of age--a longitudinal cohort study.
AB  - The objectives were to investigate the prevalence and predictors for falls and
      dizziness among people younger and older than 80 years of age. The sample was
      drawn from the Swedish National study on Aging and Care (SNAC) and comprised 973
      and 1273 subjects with data on the occurrence of falls and dizziness respectively
      at baseline. Follow-ups were made after 3- and 6-years. Data included socio
      demographics, physical function, health complaints, cognition, quality of life
      and medications. The prevalence of falls was 16.5% in those under aged 80 and
      31.7% in those 80+ years while dizziness was reported by 17.8% and 31.0%
      respectively. Predictors for falls in those under aged 80 were neuroleptics,
      dependency in personal activities of daily living (PADL), a history of falling,
      vision impairment and higher age, and in those 80+ years a history of falling,
      dependency in instrumental activities of daily living (IADL), fatigue and higher
      age. Factors predicting dizziness in those under aged 80 were a history of
      dizziness, feeling nervous and reduced grip strength and in those 80+ years a
      history of dizziness and of falling. Predictors for falls and dizziness differed
      according to age. Specific factors were identified in those under aged 80. In
      those 80+ years more general factors were identified implying the need for a
      comprehensive investigation to prevent falls. This longitudinal study also showed
      that falling and dizziness in many older people are persistent and therefore
      should be treated as chronic conditions.

PMID- 22999307
TI  - Chemoproteomic profiling identifies changes in DNA-PK as markers of early dengue
      virus infection.
AB  - Many cellular factors are regulated via mechanisms affecting protein
      conformation, localization, and function that may be undetected by most commonly
      used RNA- and protein-based profiling methods that monitor steady-state gene
      expression. Mass-spectrometry-based chemoproteomic profiling provides
      alternatives for interrogating changes in the functional properties of proteins
      that occur in response to biological stimuli, such as viral infection. Taking
      dengue virus 2 (DV2) infection as a model system, we utilized reactive ATP- and
      ADP-acyl phosphates as chemical proteomic probes to detect changes in host kinase
      function that occur within the first hour of infection. The DNA-dependent protein
      kinase (DNA-PK) was discovered as a host enzyme with significantly elevated probe
      labeling within 60 min of DV2 infection. Increased probe labeling was associated
      with increased DNA-PK activity in nuclear lysates and localization of DNA-PK in
      nucleoli. These effects on DNA-PK were found to require a postfusion step of DV2
      entry and were recapitulated by transfection of cells with RNA corresponding to
      stem loop B of the DV2 5' untranslated region. Upon investigation of the
      potential downstream consequences of these phenomena, we detected a modest but
      significant reduction in the interferon response induced by DV2 in cells
      partially depleted of the Ku80 subunit of DNA-PK. These findings identify changes
      in DNA-PK localization and activity as very early markers of DV2 infection. More
      broadly, these results highlight the utility of chemoproteomic profiling as a
      tool to detect changes in protein function associated with different cell states
      and that may occur on very short time scales.

PMID- 22999308
TI  - Granddaughter's somersault treats cupulolithiasis of the horizontal semicircular
      canal.
AB  - We report on a 61-year-old woman with cupulolithiasis of the right horizontal
      semicircular canal, which is usually difficult to treat. The patient reported
      that several years ago, similar symptoms relieved completely after having
      performed several somersaults together with her granddaughter. This time,
      repetitive somersaults were again effective to treat her benign paroxysmal
      positional vertigo. Acceleration during a somersault may induce an
      intracanalicular force strong enough to detach otoconia debris from the cupula.
      Rolling may then promote their reentrance into the utricle. This case suggests
      that repetitive somersaults may be an alternative treatment of cupulolithiasis of
      the horizontal semicircular canal.

PMID- 22999309
TI  - Autophagy impairment: a crossroad between neurodegeneration and tauopathies.
AB  - Most neurodegenerative diseases involve the accumulation of misfolded proteins in
      the nervous system. Impairment of protein degradation pathways such as autophagy
      is emerging as a consistent and transversal pathological phenomenon in
      neurodegenerative diseases, including Alzheimer's, Huntington's, and Parkinson's
      disease. Genetic inactivation of autophagy in mice has demonstrated a key role of
      the pathway in maintaining protein homeostasis in the brain, triggering massive
      neuronal loss and the accumulation of abnormal protein inclusions. However, the
      mechanism underlying neurodegeneration due to autophagy impairment remains
      elusive. A paper in Molecular Neurodegeneration from Abeliovich's group now
      suggests a role for phosphorylation of Tau and the activation of glycogen
      synthase kinase 3beta (GSK3beta) in driving neurodegeneration in autophagy
      deficient neurons. We discuss the implications of this study for understanding
      the factors driving neurofibrillary tangle formation in Alzheimer's disease and
      tauopathies.

PMID- 22999310
TI  - Identification of irradiated meats by determining o- and m-tyrosine as markers.
AB  - To identify the irradiated meats, various parameters that affect extraction
      efficiency of tyrosine positional isomers were evaluated. The optimum procedure
      employed simple extraction by 0.1% formic acid and protein precipitation by
      acetone. Baseline separation for the extract was carried out on LC-fluorescence
      detection (FLD) and LC-tandem mass spectrometry (MS/MS). The LC-FLD and LC-MS/MS
      method had LOD of 1.7-2.1 and 0.3-0.5 ng/mL, respectively, and showed excellent
      linear correlation over three orders of magnitude, obtained ideal recoveries
      (78.68-88.90%) and RSD (<= 8%). The methods were successfully applied in multiple
      samples. For o- and m-tyrosine, the order of descending trend was: chicken>beef >
      hairtail > pork and chicken > hairtail > beef > pork, respectively. The radiation
      dose could be quantitatively evaluated by the nonlinear correlation (y = A(0) x
      (2) + A(1)x + A(2)) with coefficients of determination r(2) > 0.998 in individual
      meat samples.

PMID- 22999311
TI  - Effect of the addition of tomato paste on the nutritional and sensory properties
      of mortadella.
AB  - The aim of this study was to evaluate the effect of the addition of tomato paste
      (TP) to sausage mortadella in order to improve the nutritional properties and
      reduce the lipid oxidation associated with the content of lycopene. First, three
      different mortadellas without colourant were made with 2, 6 and 10% of TP, to
      optimise technologically the amount of this ingredient. Then, commercial product
      was compared with 10% of TP mortadella; both products were made with natural
      colourant. After a proximate analysis only total protein decreased due to the
      addition of TP. Lycopene content in mortadella and the total antioxidant activity
      were proportional to the amount of TP added. The presence of TP provided
      stability during meat grinding, cooking and storage of mortadella by reducing the
      lipid oxidation. In addition, TP provided yellowness and softness; however, when
      TP was added together with red colourant, the redness remained constant in the
      mortadella without effects on the consumer overall acceptance.

PMID- 22999312
TI  - Effect of modified atmosphere and vacuum packaging on some quality
      characteristics and the shelf-life of "morcilla", a typical cooked blood sausage.
AB  - The effect of modified atmosphere and vacuum packaging on the shelf-life of
      "morcilla", a traditional cooked blood sausage, was investigated. A total of 99
      "morcillas" were packaged under vacuum and in modified atmosphere using three
      different gas mixtures: 15:35:50/O(2):N(2):CO(2) (atmosphere 1), 60:40/N(2):CO(2)
      (atmosphere 2) and 40:60/N(2):CO(2) (atmosphere 3), and stored during 2, 4, 6 and
      8 weeks at 4  degrees C. Shelf life evaluation was based on pH, water activity
      (a(w)), colour (CIE L*, a*, b*, C* and h*), TBARS formation and microbial counts.
      The results indicated that, in general, storage time affected (P<0.05) all
      parameters whereas no significant differences were observed (P>0.05) among
      packaging conditions. Based on the microbial counts, the shelf-life of "morcilla"
      would be greater than 8 weeks for all packaging conditions. Samples packaged with
      high CO(2) concentrations (40:60/N(2):CO(2)) showed the lowest values of TBARS at
      the end of storage.

PMID- 22999313
TI  - RNA-binding proteins: post-transcriptional control of aging traits: an
      introduction to a series of review articles.

PMID- 22999316
TI  - [Assignment of impact factor to Gastroenterologia y Hepatologia].

PMID- 22999317
TI  - Ammonia-related changes in cerebral electrogenesis in healthy subjects and
      patients with cirrhosis.
AB  - OBJECTIVE: To study the effect of hyperammonaemia on the wake
      electroencephalogram (EEG) of patients with cirrhosis and healthy volunteers.
      METHODS: Wake EEGs were recorded prior to and after the induction of controlled
      hyperammonaemia in 10 patients with cirrhosis and 10 matched healthy volunteers.
      RESULTS: At baseline, patients had higher ammonaemia than healthy volunteers and
      their dominant EEG rhythm was slower and of higher amplitude. Induced
      hyperammonaemia resulted in increased spectral power over most of the scalp in
      healthy volunteers and decreased frequency along the anterior-posterior midline
      in patients. CONCLUSIONS: These findings suggest different effects of
      hyperammonaemia on the wake EEG in relation to baseline/peak ammonia levels.
      SIGNIFICANCE: The wake EEG is sensitive to hyperammonaemia and power-based EEG
      parameters may help in its neurophysiological definition, which, to date, has
      generally been based on EEG frequency indices.

PMID- 22999318
TI  - Visual processing in the inferior temporal cortex: an intracranial event related
      potential study.
AB  - OBJECTIVE: To investigate visual processing over the inferior temporal cortex
      (ITC) by recording intracranial event-related potentials (IERPs), and correlating
      the results with those of electrocortical stimulation mapping (ESM). METHODS:
      IERPs to word, non-word, and non-letter visual stimuli were recorded over the ITC
      in 6 patients with intractable epilepsy. Two patients underwent ESM of the same
      contacts. RESULTS: IERPs were observed at 18 electrodes in 4 out of 6 patients.
      Nine electrodes showed early IERPs (peak latency <= 200 ms) over the posterior
      and middle ITC and 7 of them showed a following late ERP component, "early+late
      IERPs". Nine electrodes showed late IERPs (peak latency>200 ms) over the middle
      and anterior ITC. Among four electrodes showing language or visual phenomena by
      ESM, one electrode showed a short latency IERP, another electrode showed a late
      IERP, and the remaining two electrodes showed no IERPs. CONCLUSIONS: Our findings
      further support that the visual recognition occurred sequentially from posterior
      to anterior ITC. Dissociation of IERPs and ESM may be explained by the
      methodological difference. SIGNIFICANCE: IERP study disclosed that visual
      recognition occurred sequentially from posterior to anterior ITC.

PMID- 22999319
TI  - Functional repetitive transcranial magnetic stimulation increases motor cortex
      excitability in survivors of stroke.
AB  - OBJECTIVE: To determine if repetitive transcranial magnetic stimulation (rTMS)
      applied to the motor cortex with simultaneous voluntary muscle activation, termed
      functional-rTMS, will promote greater neuronal excitability changes and neural
      plasticity than passive-rTMS in survivors of stroke. METHODS: Eighteen stroke
      survivors were randomized into functional-rTMS (EMG-triggered rTMS) or passive
      rTMS (rTMS only; control) conditions. Measures of short-interval intracortical
      inhibition (SICI) and intracortical facilitation (ICF), force steadiness
      (coefficient of variation, CV) at 10% of maximum voluntary contraction, and pinch
      task muscle activity were assessed before and after rTMS. Functional-rTMS
      required subjects to exceed a muscle activation threshold to trigger each rTMS
      train; the passive-rTMS group received rTMS while relaxed. RESULTS: Significant
      interactions (time * condition) were observed in abductor pollicis brevis (APB)
      SICI, APB ICF, CV of force, and APB muscle activity. Functional-rTMS decreased
      APB SICI (p < 0.05) and increased ICF (p < 0.05) after stimulation, whereas
      passive-rTMS decreased APB muscle activity (p < 0.01) and decreased CV of force
      (p < 0.05). No changes were observed in FDI measures (EMG, ICF, SICI).
      CONCLUSION(S): Functional-rTMS increased motor cortex excitability, i.e., less
      SICI and more ICF for the APB muscle. Passive stimulation significantly reduced
      APB muscle activity and improved steadiness. SIGNIFICANCE: Functional-rTMS
      promoted greater excitability changes and selectively modulated agonist muscle
      activity.

PMID- 22999320
TI  - The mosquitoes (Diptera: Culidae) of Seychelles: taxonomy, ecology, vectorial
      importance, and identification keys.
AB  - BACKGROUND: During recent periods, the islands of the Republic of Seychelles
      experienced many diseases such as dengue, chikungunya, Bancroft's filaria and
      malaria. Mosquitoes transmit the agents that cause these diseases. Published
      information on mosquitoes in the Seychelles is notably dispersed in the
      literature. The maximum number of species obtained on a single field survey does
      not exceed 14 species. METHODS: We performed a comprehensive bibliographic review
      using mosquito and Seychelles as the key words, as well as conducted a mosquito
      field survey for larval and adult stages during the rainy season in December
      2008. Sixteen sites were sampled on four granitic islands (Mahe, Praslin, La
      Digue and Aride) and six sites on coralline atolls in the extreme southwest of
      the country (Aldabra group). RESULTS: We found published references to 21
      mosquito species identified at least on one occasion in the Seychelles. Our
      collections comprised 18 species of mosquitoes, all of them from the subfamily
      Culicinae; no Anophelinae was found. We also confirm that Aedes seychellensis is
      a junior synonym of Ae. (Aedimorphus) albocephalus. The first records for Culex
      antennatus and Cx. sunyaniensis are presented from the country, specifically from
      Aldabra and Praslin, respectively. Based on a comparison of the taxa occurring on
      the granitic versus coralline islands, only three species, Ae. albocephalus, Cx.
      scottii and Cx. simpsoni are shared. Aedes albopictus appeared to exclude largely
      Ae. aegypti on the granitic islands; however, Ae. aegypti was common on Aldabra,
      where Ae. albopictus has not been recorded. The notable aggressiveness of
      mosquitoes towards humans on coralline islands was mainly due to two species, the
      females of which are difficult to distinguish: Ae. fryeri and Ae. (Aedimorphus)
      sp. A. The number of mosquito species collected at least once in the Seychelles
      is now 22, among which five species (Ae. (Adm) sp. A, Cx. stellatus, Uranotaenia
      browni. Ur. nepenthes and Ur. pandani) and one subspecies (Ae. vigilax
      vansomerenae) are considered as endemic. Two illustrated identification keys, one
      for adult females and the other for larval stages, are presented. CONCLUSIONS:
      The knowledge of the culicidian fauna in the Seychelles has been notably updated.
      The number of mosquito species is relatively large with regards to land surface
      and distances to continental Africa, although the anophelines are totally
      lacking. The complex natural history of mosquitoes in the Seychelles provides
      examples of both vicariance- and dispersal-mediated divergences. They present
      superb examples for theoretical and applied island biology.

PMID- 22999322
TI  - Practice and challenges of thorough QT studies.
AB  - The drug-induced Torsade de Pointes (TdP) tachycardia is a known regulatory
      problem which led to the concept of the so-called thorough QT (TQT) studies now
      required for practically every new pharmaceutical compound. This review
      summarizes the concept of the TQT studies, their statistical evaluation, and
      related pharmacodynamic /pharmacokinetic modeling. The review also lists
      suggestions of how to make TQT studies more efficient and how to improve the
      interpretation of clinical data obtained during drug development to identify
      drugs prone to TdP induction more effectively.

PMID- 22999321
TI  - Elevated pulmonary artery systolic pressures are associated with a lower risk of
      atrial fibrillation following lung transplantation.
AB  - BACKGROUND: Atrial fibrillation (AF) is common after open-chest procedures, but
      the etiology remains poorly understood. Lung transplant procedures allow for the
      study of novel contributing factors. METHODS: Records of lung transplant
      procedures performed at a single center between 2002 and 2009 were reviewed.
      RESULTS: Of 174 patients, 27 (16%) had AF a median 6 days post-surgery. Post
      operative AF patients less often had right ventricular hypertrophy (RVH) by
      either electrocardiogram (0 versus 14%, P=.042) or echocardiography (19% versus
      47%, P=.006), and had lower pulmonary artery systolic pressures (PASP) (39 +/- 12
      versus 51 +/- 22, P=.005). After multivariable adjustment, every 10-mm Hg
      increase in PASP was associated with a 31% reduction in the odds of post
      operative AF (OR 0.69, 95% CI 0.49-0.98, P=.035). A higher pulmonary pressure was
      the only predictor independently associated with less post-operative AF.
      CONCLUSIONS: Higher PASP was associated with a lower risk of AF after lung
      transplantation.

PMID- 22999323
TI  - Selection of high-risk patients for device intervention with the new advances in
      technology.
AB  - The recent clinical therapeutic studies involving high-risk cardiac patients with
      genetic or acquired heart disease provide valuable insights into the potential
      for new advances in the technology for improving risk stratification to identify
      patients who can benefit from device therapy.

PMID- 22999324
TI  - Drug-induced QT-interval prolongation and recurrent torsade de pointes in a child
      with heterotaxy syndrome and KCNE1 D85N polymorphism.
AB  - We present a child case of heterotaxy syndrome (asplenia syndrome) after Fontan
      procedure that showed extreme prolongation of QT interval and torsade de pointes
      (TdP) after administration of sodium channel blockers for paroxysmal atrial
      tachycardia. Despite low serum concentration of the drugs, QT prolongation
      persisted and TdP attacks with unconsciousness recurred, possibly in association
      with junctional bradycardia and myocardial damage although he had never
      experienced QT prolongation during bradycardia before. Temporal cardiac pacing
      via a venous route to exclude possible implication of bradycardia in induction of
      TdP was difficult to apply due to total cavopulmonary connection (TCPC)
      circulation. Continuous intravenous administration of low-dose isoproterenol was
      started but an appropriate heart rate for prevention of TdP was difficult to
      obtain. Finally, we were urged to conduct implantation of a DDD pacemaker
      combined with ICD surgically with epicardial leads, resulting in successful
      suppression of TdP and syncope. Screening of the genotype disclosed the KCNE1
      D85N polymorphism, which is known as one of the typical disease-causing gene
      variants in long-QT syndrome (LQTS).

PMID- 22999325
TI  - Importance of subject-specific QT/RR curvatures in the design of individual heart
      rate corrections of the QT interval.
AB  - OBJECTIVE: A statistical modelling study investigated whether incorporating the
      curvatures of QT/RR patterns into the individual-specific QT heart rate
      correction increases QTc data accuracy. METHODS: Repeated ECG readings were
      available from 4 different drug-free recordings made in 176+176 healthy female
      and male subjects (aged 32 +/- 10 and 33 +/- 8 years, respectively). In each
      subject, up to 1440 ECG readings were made of QT intervals and of the
      corresponding QT/RR hysteresis corrected RR intervals. The QT/RR patterns of each
      study participant was fitted with 12 different regression formulae that
      corresponded to differently curved physiologically plausible QT/RR profiles. In
      each subject, each of the regression fits was converted into a QT heart rate
      correction formula and the optimum model that fitted the data of the subject best
      was identified. Correction formulae were applied to modelled QT/RR data with RR
      intervals between 400 ms and 1600 ms. Differences in QTc intervals calculated by
      the correction formulae corresponding to the individually optimum QT/RR
      regression models and by the same type of regression in all study subjects were
      statistically summarised in females and males. RESULTS: Compared to the
      individually curvature optimised QTc heart rate correction formulae, formulae of
      the different regression models overestimated or underestimated the QTc values
      when applied on all study subjects. At RR of 500 ms, the model assuming linear
      QT/RR relationship led to errors of -5.01 +/- 6.63 ms and of -4.80 +/- 7.23 ms in
      females and males, respectively. At the same RR interval level, the model
      assuming the linear relationship between the logarithms of QT and RR intervals
      led to errors of +11.51 +/- 6.36 ms and of +15.09 +/- 7.61 ms in females and
      males, respectively. CONCLUSION: The differences in the curvatures of QT/RR
      patterns should be considered in the optimisation of subject-specific heart rate
      corrections. Forcing an arbitrary simple regression model on the QT/RR patterns
      of different subjects may lead to appreciable errors in QTc estimates. The
      frequently used linear and log-linear regression models were among the least
      precise if used without checking their appropriateness in individual subjects.

PMID- 22999326
TI  - Socio-economic inequalities: a review of methodological issues and the
      relationships with cancer survival.
AB  - During the past few decades, many studies on socio-economic factors and health
      outcomes have been developed using various methodologies with differing
      approaches. A bibliographic research in MEDLINE/PubMed and SCOPUS was carried out
      for the period 2000-2011 to describe the influence of socio-economic status (SES)
      on cancer survival, in particular with reference to the outcome of European
      research results and the results of some cases of other Western studies. This
      review is divided into two sections: the first describing the different
      approaches of the study on individuals and populations of the concept of "social
      class" as well as methods used to measure the association between deprivation and
      health (i.e. ecological level studies, deprivation indexes, etc.); and the second
      discussing the association between socio-economic factors and cancer survival,
      describing the roles of various determinants of differences in survival, such as
      clinical and pathological prognostic factors, together with consideration of
      diagnosis and treatment and some patients' characteristics.

PMID- 22999327
TI  - Laparoscopic vs open pancreaticoduodenectomy: overall outcomes and severity of
      complications using the Accordion Severity Grading System.
AB  - BACKGROUND: Minimal access surgery techniques have evolved to include complex
      surgical procedures. Laparoscopic pancreaticoduodenectomy (LPD) is a complex
      operation that pancreas surgeons have been slow to adopt. This article reviews
      our experience with patients undergoing LPD and compares their outcomes with
      those of patients undergoing open pancreaticoduodenectomy (OPD). STUDY DESIGN:
      All patients undergoing OPD or LPD during a 6-year period (2005-2011) were
      included. Results from the 2 groups were compared for mortality and morbidity
      according to the Accordion Severity Grading System. Oncologic markers, including
      margins of resection, transfusions received, number of lymph nodes, and lymph
      node ratio, were also compared. RESULTS: During the study time period, 215 and 53
      patients underwent OPD and LPD, respectively. No differences were seen in patient
      demographics, comorbidities, American Society of Anesthesiologists grade, or
      pathology. Significant differences favoring LPD were seen in intraoperative blood
      loss (p < 0.001), transfusions (p < 0.001), length of hospital stay (p < 0.001),
      and length of ICU stay (p < 0.001). Operative time was significantly longer for
      LPD (p < 0.001). There were no differences in overall complications, pancreas
      fistula, or delayed gastric emptying. Oncologic outcomes demonstrated no
      significant differences in resection margins, size of tumor, or T/N stages. There
      were significant differences in number of lymph nodes retrieved (p = 0.007) and
      lymph node ratio (p < 0.001) in favor of LPD. CONCLUSIONS: This series
      demonstrates that LPD appears to be safe and feasible, with benefits over the
      open counterpart. However, the increased complexity and effort demanded by the
      technique pose the need for multi-institutional series and standardization in
      reporting. The goal should be to assess if LPD can result in a better procedure
      with better outcomes.

PMID- 22999328
TI  - Modified hernia grading scale to stratify surgical site occurrence after open
      ventral hernia repairs.
AB  - BACKGROUND: The lack of a universally accepted classification system for
      incisional hernia repair has led to inconsistent reporting of ventral hernia
      repairs, the inability to compare various series, and the lack of appropriate
      risk adjusted stratification systems to evaluate surgical outcomes. This study
      evaluates the Ventral Hernia Working Group's (VHWG) grading scale to accurately
      predict surgical site occurrence (SSO) after open ventral hernia repair. STUDY
      DESIGN: All open ventral hernia repairs performed at Case Medical Center were
      evaluated from a prospectively maintained database. Hernias were graded according
      to the VHWG grading scale, and patients were evaluated for the incidence of a
      SSO. The relationships between comorbidities, hernia defect characteristics, CDC
      wound classification, and SSOs were also evaluated. RESULTS: There were 299
      patients who met inclusion criteria and were available for follow-up. Surgical
      site occurrence was identified in 14% grade 1, 29% grade 2, 38% grade 3, and 49%
      grade 4 patients (p = 0.003). However, grade 3 patients with only a previous
      wound infection had a significantly different incidence of SSO than those with a
      violation of the gastrointestinal (GI) tract and were actually more similar to
      grade 2 patients. Likewise, violation of the GI tract had a similar rate of SSO
      to grade 4 patients. Finally, CDC wound classification also accurately predicted
      SSO across all levels of contamination. CONCLUSIONS: Modification of the VHWG
      grading scale into a 3-level grading system would significantly improve the
      accuracy of predicting SSO after open ventral hernia repair. Grade 2 patients
      should include those with comorbidities and previous wound infections. Grade 3
      patients should be stratified based on CDC definitions of wound contamination.
      This modified grading scale would significantly improve outcomes reporting after
      open ventral hernia repair.

PMID- 22999329
TI  - In-hospital and long-term outcomes after percutaneous endoscopic gastrostomy in
      patients with malignancy.
AB  - BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) is widely
      performed for nutrition or palliation, PEG-associated outcomes in cancer patients
      remain poorly described. We examined the safety and benefits of PEG placement in
      this population at our institution. STUDY DESIGN: A 5-year retrospective review
      of patients with malignancy (excluding head/neck and thoracic malignancy) who
      underwent PEG at our institution was performed. RESULTS: One hundred and eighty
      nine patients with malignancy underwent PEG; 33.9% had hematologic malignancy,
      66.1% had nonhematologic malignancy, and 44.4% had metastatic disease.
      Indications for PEG were enteral access (73%) and gastric
      decompression/management of obstructive symptoms (27%). Few patients achieved
      independence from total parenteral nutrition (22%) or diet advancement (24.6%).
      Overall rates of major complications (eg, aspiration, tube dislodgement/leakage,
      bleeding, visceral injury, respiratory failure after procedure, and cardiac
      arrest) and minor complications (eg, superficial infection and ileus) were 10.2%
      and 11.3%, respectively. All-cause in-hospital mortality was high (19.6%) and was
      associated with ICU admission (p = 0.018), earlier bone marrow transplantation (p
      = 0.022), steroid treatment (p = 0.024), and lower preoperative albumin (p =
      0.003). Code status was changed after PEG in 44 patients from full code to DNR/do
      no intubate or comfort measures only. CONCLUSIONS: Percutaneous endoscopic
      gastrostomy placement in this study population was associated with major
      procedure-related complications. The majority of patients failed to achieve total
      parenteral nutrition independence or advancement of diet. Nearly 25% of patients
      declined aggressive resuscitation strategies after undergoing surgery for PEG.
      This study cautions to carefully weigh the risks and benefits of PEG placement in
      this patient population. Prospective studies are needed to uncover factors
      affecting the decision process and patient selection.

PMID- 22999330
TI  - Resident participation in index laparoscopic general surgical cases: impact of
      the learning environment on surgical outcomes.
AB  - BACKGROUND: The NSQIP database enables measurement of postoperative outcomes
      across a spectrum of practice settings. This allows for observations about
      potential effects of resident participation in surgical care during training.
      STUDY DESIGN: We queried the NSQIP database for 6 index laparoscopic surgical
      procedures performed during 2005-2008. Selected procedures require varying skill
      level (eg, appendectomy, cholecystectomy, gastric bypass, fundoplication,
      colectomy, and inguinal hernia), and 79,720 cases were identified. Preoperative,
      operative, and postoperative outcomes for each procedure were tabulated.
      Operative and postoperative outcomes assessed included operative time, hospital
      length of stay, mortality, morbidity, and return to the operating room. Initial
      analysis compared cases done with a resident present with cases done without
      residents. Subset analysis was done to determine possible differences in outcomes
      based on the level of resident participating, divided into Junior (PGY1-2),
      Senior (PGY3-5), or Fellow (PGY>5). Groups were scrutinized for both clinical and
      statistical differences. RESULTS: Preoperative characteristics were similar
      between groups. Operative times were 20% to 47% longer with resident
      participation, with bigger differences seen in more basic procedures. Mortality
      and return to the operating room were not clinically different between the
      groups. Morbidity rates were higher in all procedures with resident
      participation. More senior residents were associated with longer operative times,
      without adverse impact on outcomes. CONCLUSIONS: Resident participation increases
      operative times for laparoscopic surgery considerably. Morbidity is statistically
      higher with resident participation but differences are unlikely to be clinically
      significant. Resident participation is a surrogate for the learning environment.
      These findings provide impetus for additional development of training techniques
      that occur outside the operating room.

PMID- 22999331
TI  - Physiotherapy intervention for preventing the respiratory muscle deterioration in
      institutionalized older women with functional impairment.
AB  - INTRODUCTION: In elderly seniors (>80 years), respiratory function may be
      compromised when, in addition to the presence of comorbidity and loss of
      mobility, there is also reduced respiratory muscle (RM) strength. The literature
      has shown that RM training could be an effective method to improve RM function
      and prevent clinical deterioration, particularly in population with RM weakness.
      The main purpose of this paper was to assess the effectiveness of RM training on
      the respiratory muscle strength and endurance of institutionalized elderly women
      with functional impairment. METHOD: Fifty-four residents (mean=85 years, SD=6.7)
      were randomly assigned to either a control (n=27) or training (n=27) group. A
      supervised training program was developed with Threshold((r))IMT, five times per
      week for 6-weeks. The main variables of the intervention were: maximum
      inspiratory pressure (PI(max)), maximum expiratory pressure (PE(max)) and maximal
      voluntary ventilation (MVV), all of which were measured at weeks 0, 4, 7 and 10.
      RESULTS: Statistical analysis revealed no significant differences in PI(max)
      (F(3,114)=1.04, p=0.368, R(2)=0.027), PE(max) (F(3,114)=1.86, p=0.14, R(2)=0.047)
      and MVV (F(3,114)=1.74, p=0.162, R(2)=0.044) between the two groups after the
      intervention. However, the workload significantly improved with the training
      sessions (F(5,100)=72.031, p<0.001, R(2)=0.791). CONCLUSION: In a 6-week interval
      based training program, the threshold loading device does not significantly
      improve parameters related to RM strength and endurance of the study population.

PMID- 22999333
TI  - First report of a Wautersiella falsenii isolated from the urine of an infant with
      pyelonephritis.
AB  - Here, we report the first isolation of Wautersiella falsenii from the urine of an
      infant with a complicated urinary tract infection. W. falsenii was correctly
      identified by matrix-assisted laser desorption ionisation time of flight mass
      spectrometry. The identification was confirmed by 16S polymerase chain reaction.
      Susceptibility test results of this isolate are reported. Ciprofloxacin treatment
      resulted in clinical and microbiological improvement.

PMID- 22999332
TI  - Rapid identification of pathogens from positive blood cultures by multiplex
      polymerase chain reaction using the FilmArray system.
AB  - Sepsis is a leading cause of death. Rapid and accurate identification of
      pathogens and antimicrobial resistance directly from blood culture could improve
      patient outcomes. The FilmArray(r) (FA; Idaho Technology, Salt Lake City, UT,
      USA) Blood Culture (BC) panel can identify >25 pathogens and 4 antibiotic
      resistance genes from positive blood cultures in 1 h. We compared a development
      version of the panel to conventional culture and susceptibility testing on 102
      archived blood cultures from adults and children with bacteremia. Of 109
      pathogens identified by culture, 95% were identified by FA. Among 111
      prospectively collected blood cultures, the FA identified 84 (91%) of 92
      pathogens covered by the panel. Among 25 Staphylococcus aureus and 21
      Enterococcus species detected, FA identified all culture-proven methicillin
      resistant S. aureus and vancomycin-resistant enterococci. The FA BC panel is an
      accurate method for the rapid identification of pathogens and resistance genes
      from blood culture.

PMID- 22999334
TI  - Rosiglitazone negatively regulates c-Jun N-terminal kinase and toll-like receptor
      4 proinflammatory signalling during initiation of experimental aortic aneurysms.
AB  - OBJECTIVE: Development and rupture of aortic aneurysms (AA) is a complex process
      involving inflammation, cell death, tissue and matrix remodelling. The
      thiazolidinediones (TZDs) including Rosiglitazone (RGZ) are a family of drugs
      which act as agonists of the nuclear peroxisome proliferator-activated receptors
      and have a broad spectrum of effects on a number of biological processes in the
      cardiovascular system. In our previous study we have demonstrated that RGZ has a
      marked effect on both aneurysm rupture and development, however, the precise
      mechanism of this is unknown. METHODS AND RESULTS: In the present study, we
      examined possible targets of RGZ action in the early stages of Angiotensin II
      induced AA in apolipoprotein E-deficient mice. For this purpose we employed
      immunoblotting, ELISA and antibody array approaches. We found that RGZ
      significantly inhibited c-Jun N-terminal kinase (JNK) phosphorylation and down
      regulated toll-like receptor 4 (TLR4) expression at the site of lesion formation
      in response to Angiotensin II infusion in the initiation stage (6-72 h) of
      experimental AA development. Importantly, this effect was also associated with a
      decrease of CD4 antigen and reduction in production of TLR4/JNK-dependant
      proinflammatory chemokines MCP-1 and MIP-1alpha. CONCLUSION: These data suggest
      that RGZ can modulate inflammatory processes by blocking TLR4/JNK signalling in
      initiation stages of AA development.

PMID- 22999335
TI  - The genes in the major histocompatibility complex as risk factors for
      schizophrenia: de omnibus dubitandum.

PMID- 22999336
TI  - Brain copy number variants and neuropsychiatric traits.

PMID- 22999337
TI  - Isolation and characterization of ovine mesenchymal stem cells derived from
      peripheral blood.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem cells with
      capacity to differentiate into several mesenchymal lineages. This quality makes
      MSCs good candidates for use in cell therapy. MSCs can be isolated from a variety
      of tissues including bone marrow and adipose tissue, which are the most common
      sources of these cells. However, MSCs can also be isolated from peripheral blood.
      Sheep has been proposed as an ideal model for biomedical studies including those
      of orthopaedics and transmissible spongiform encephalopathies (TSEs). The aim of
      this work was to advance these studies by investigating the possibility of MSC
      isolation from ovine peripheral blood (oPB-MSCs) and by subsequently
      characterizing there in vitro properties. RESULTS: Plastic-adherent fibroblast
      like cells were obtained from the mononuclear fraction of blood samples. These
      cells were analysed for their proliferative and differentiation potential into
      adipocytes, osteoblasts and chondrocytes, as well as for the gene expression of
      cell surface markers. The isolated cells expressed transcripts for markers CD29,
      CD73 and CD90, but failed to express the haematopoietic marker CD45 and expressed
      only low levels of CD105. The expression of CD34 was variable. The
      differentiation potential of this cell population was evaluated using specific
      differentiation media. Although the ability of the cultures derived from
      different animals to differentiate into adipocytes, osteoblasts and chondrocytes
      was heterogeneous, we confirmed this feature using specific staining and
      analysing the gene expression of differentiation markers. Finally, we tested the
      ability of oPB-MSCs to transdifferentiate into neuronal-like cells. Morphological
      changes were observed after 24-hour culture in neurogenic media, and the
      transcript levels of the neurogenic markers increased during the prolonged
      induction period. Moreover, oPB-MSCs expressed the cellular prion protein gene
      (PRNP), which was up-regulated during neurogenesis. CONCLUSIONS: This study
      describes for the first time the isolation and characterization of oPB-MSCs.
      Albeit some variability was observed between animals, these cells retained their
      capacity to differentiate into mesenchymal lineages and to transdifferentiate
      into neuron-like cells in vitro. Therefore, oPB-MSCs could serve as a valuable
      tool for biomedical research in fields including orthopaedics or prion diseases.

PMID- 22999338
TI  - Circulating biomarkers of collagen type I metabolism mark the right ventricular
      fibrosis and adverse markers of clinical outcome in adults with repaired
      tetralogy of Fallot.
AB  - BACKGROUND: Right ventricular (RV) fibrosis is common in patients with repaired
      tetralogy of Fallot (rTOF). Although accumulating evidence indicates the role of
      circulating biomarkers of collagen metabolism in left ventricular fibrosis, rTOF
      data are lacking. This study examined the expression profile and clinical
      relevance of circulating biomarkers of collagen type I metabolism in rTOF
      patients. METHODS: Serum biomarkers of collagen type I synthesis (carboxy
      terminal propeptide of procollagen type I, PICP), degradation (carboxy-terminal
      telopeptide of collagen type I, CITP), and enzymes regulating collagen
      degradation (matrix metalloproteinases, and type I tissue inhibitor, TIMP-1) were
      measured in 70 rTOF and 91 control adults. All patients had complete clinical
      data and received cardiovascular magnetic resonance scans with late gadolinium
      enhancement (LGE). RESULTS: Compared to the controls, rTOF patients had higher
      PICP levels (p<0.001), PICP:CITP ratios (p<0.001), and TIMP-1 concentrations
      (p<0.001). Increasing PICP levels correlated with higher RV LGE scores (r=0.427,
      p<0.001), lower VO2max (r=-0.428, p=0.002), and larger RV volumes. Furthermore,
      stepwise multivariate linear regression analysis identified RV end-diastolic
      volume index >150mL/m(2) (beta=40.52, p=0.016), RV LGE score (beta=3.94,
      p=0.008), and age (beta=-1.77, p=0.011) as independent correlates of circulating
      PICP levels. CONCLUSIONS: Patients with rTOF exhibited a profibrotic state with
      excessive collagen type I synthesis and dysregulated degradation. Elevated
      circulating PICP levels might reflect RV fibrosis, and link to adverse markers of
      clinical outcome.

PMID- 22999339
TI  - Leonardo da Vinci and the first portrayal of quadricuspid semilunar valves and
      the nodules of Arantius.

PMID- 22999340
TI  - Strut fractures of CoreValve frames.

PMID- 22999341
TI  - Unusual long left anterior descending coronary artery with a posterior
      "ascending" branch.

PMID- 22999342
TI  - Comparison of three-dimensional volume-targeted thin-slab FIESTA magnetic
      resonance angiography and 64-multidetector computed tomographic angiography for
      the identification of proximal coronary stenosis.
AB  - BACKGROUND: Based on recent clinical data, an imaging strategy of identifying
      proximal coronary disease allows further management decisions in patients with
      stable angina pectoris. We aimed to compare diagnostic accuracy of non-contrast
      fast steady-state (FIESTA) magnetic resonance angiography (MRA) with 64
      multidetector computed tomographic angiography (CTA), using conventional coronary
      angiography (CA) as the reference standard. METHODS: Thirty patients with
      suspected coronary artery disease consented to participate in an institutional
      review board-approved protocol. Coronary MRA was performed at 1.5 T using a
      respiratory navigator and electrocardiogram-gated three-dimensional FIESTA pulse
      sequence. CTA images were acquired using a 64-multidetector computed tomographic
      scanner, using beta blockade to reduce the heart rate to less than 70 bpm.
      Coronary luminal stenosis >50% was identified. Plaques were classified as non
      calcified, mixed, or calcified on CTA, and as high-, intermediate-, or low-signal
      on FIESTA MRA. RESULTS: Compared to CA, the sensitivity, specificity, and overall
      accuracy for detection of >50% proximal coronary stenoses were 83.0%, 86.9%, and
      86.1% for MRA and 85.1%, 87.2%, and 86.8% for CTA, respectively. For the 24
      calcified stenoses, MRA corrected 16 segments that overestimated on CTA and MRA
      had an accuracy of 75% in evaluating calcified plaques. CONCLUSIONS: High
      resolution three-dimensional FIESTA MRA and CTA have a similar accuracy in
      detecting proximal coronary stenosis. The clinical impact of identification of
      proximal disease in patients with stable CAD needs to be examined in future
      studies.

PMID- 22999343
TI  - Parity and aortic dimensions in healthy women.

PMID- 22999344
TI  - Serial spontaneous coronary artery dissections: a transient predisposition
      affecting multiple coronary arteries?

PMID- 22999345
TI  - [Current state of single-port transumbilical surgery in urology: challenges and
      applications].
AB  - CONTEXT: Laparoscopic surgery in urology is considered to be an important
      advance, although it is not exempt from some morbidity associated to the use of
      multiple trocars and specifically to the extraction of the specimen. In order to
      decrease this morbidity and improve esthetics, other techniques are being
      developed, such as natural orifice transluminal endoscopic surgery (NOTES) and
      laparoendoscopic single-site surgery (LESS). It is aimed to review the current
      status of laparoendoscopic single site surgery in urology. ACQUISITION OF
      EVIDENCE: A nonsystematic review has been carried out by means of the
      bibliographic search using the terms LESS and Urology from 2007 to 2012. The
      current LESS experience in urology is described, and its principal indications
      and the different single site devices and instruments available on the market are
      described. SYNTHESIS OF EVIDENCE: LESS surgery arose as one more step in the
      constant evolution of minimally invasive surgery in an attempt to improve
      esthetics, reduce surgical trauma and decrease pain and the post-operative
      complications associated to the conventional laparoscopy with multiple trocars.
      Since it was first described in 2007, the experience has been increasing
      exponentially and the LESS technique, whether assisted or not by robot, is
      becoming consolidated for a large spectrum of urological indications (both in
      oncological and reconstructive surgery) on a much greater scale than the NOTES
      technique. Even though most of the existing data are not randomized and very
      rarely comparative, with the selection bias that this represents, it seems clear
      that the esthetic benefit and analgesic control associated to the LESS surgery is
      real and reproducible. The complications associated to it are greater in cases of
      major oncology surgery and are due more to the technique itself then to the
      approach. CONCLUSIONS: Although the real benefit of the LESS surgery in urology
      cannot be appropriately quantified, the cosmetic improvement, less pain and
      greater patient satisfaction with their wound are clear. Appropriate training in
      this type of procedures in centers having large volumes and the continuous
      technical improvements in the instrumental development by the biomedical industry
      has resulted in the fact that the transumbilical LESS technique in urology has
      been born to stay.

PMID- 22999346
TI  - [Subepithelial pelvic hematoma].
AB  - INTRODUCTION: Subepithelial pelvic hematoma (Antopol Goldman lesion) is a rare
      condition that may clinical and radiologically simulate a renal or pelvic
      neoplasm and whose final diagnosis has been established after nephrectomy in most
      published cases. To avoid misdiagnosis, imaging tests and high diagnostic
      suspicion are essential. MATERIAL AND METHODS: We present the case of a 43-year
      old woman with no background of interest who was admitted to our Hospital
      complaining of acute left flank pain after a physical effort. The patient was
      studied by Ultrasonography, Computed Tomography and evolutively by Magnetic
      Resonance Imaging. RESULTS: The radiologic exams showed a lesion in the left
      renal sinus with characteristics suggestive of subepithelial pelvic hematoma and
      without data revealing any underlying lesion. The patient was treated
      conservatively and follow-up examinations confirmed the disappearance of the
      lesion. CONCLUSION: Knowledge of the radiologic features of Antopol Goldman
      lesion as well as a high degree of clinical suspicion are crucial in the
      management of patients affected by this uncommon condition and may avoid an
      unnecessary nephrectomy.

PMID- 22999347
TI  - [Recomendations on the management of controversies in advanced castrate-resistant
      prostate cancer].
AB  - CONTEXT: Controversies and uncertainties among integral management of advanced
      castration resistant prostate cancer continue to exist despite the number of
      evidence based clinical practice guidelines published with high international
      consensus. OBJECTIVE: To develop a document that reviews the management of
      controversies in advanced castration resistant prostate cancer, with
      recommendations from the definition, to the management in hormonal maneuvers,
      first-line treatment and second-line with new treatments as cabazitaxel or
      abirarerone and the multidisciplinary approach of the pathology with the goal of
      finding the most efficient, best time to act and safety. EVIDENCE ACQUISITION:
      Two meetings of a multidisciplinary group of experts involved in the management
      of this disease (Oncologist and Urologist) where pooled analysis of original
      literature and reached consensus document of recommendations on castration
      resistant prostate cancer, reviewing and attempting to address the current
      controversies of the disease. EVIDENCE SYNTHESIS: This document is endorsed by
      the corresponding Scientific Associations and Working Groups involved in the
      current management of Genitourinary Tumours: the Spanish Association of Urology
      (AEU) with the Uro-Oncoloy Group (GUO) and the Spanish Oncology of Genitourinary
      Group (SOGUG). CONCLUSIONS: With the adaptation and implementation of this
      Document of Recommendations for clinical practice are available for the first
      time, a real road map for quality, efficiency and safety in the management of
      patients with CRPC.

PMID- 22999348
TI  - Tracing fatty acid metabolism by click chemistry.
AB  - Fatty acids are abundant constituents of all biological systems, and their
      metabolism is important for normal function at all levels of an organism.
      Aberrations in fatty acid metabolism are associated with pathological states and
      have become a focus of current research, particularly due to the interest in
      metabolic overload diseases. Here we present a click-chemistry-based method that
      allows tracing of fatty acid metabolism in virtually any biological system. It
      combines high sensitivity with excellent linearity and fast sample turnover.
      Since it is free of radioactivity, it can be combined with any other modern
      analysis technology and can be used in high-throughput applications. Using the
      new method, we provide for the first time an analysis of cellular fatty
      metabolism with high time resolution and a comprehensive comparison of
      utilization of a broad spectrum of fatty acids in hepatoma and adipose cell
      lines.

PMID- 22999351
TI  - The United States 2012 general election: making children's health and well-being
      a priority for the candidates.

PMID- 22999350
TI  - Catching the engram: strategies to examine the memory trace.
AB  - Memories are stored within neuronal ensembles in the brain. Modern genetic
      techniques can be used to not only visualize specific neuronal ensembles that
      encode memories (e.g., fear, craving) but also to selectively manipulate those
      neurons. These techniques are now being expanded for the study of various types
      of memory. In this review, we will summarize the genetic methods used to
      visualize and manipulate neurons involved in the representation of memory
      engrams. The methods will help clarify how memory is encoded, stored and
      processed in the brain. Furthermore, these approaches may contribute to our
      understanding of the pathological mechanisms associated with human memory
      disorders and, ultimately, may aid the development of therapeutic strategies to
      ameliorate these diseases.

PMID- 22999352
TI  - The Patient Protection and Affordable Care Act and the future of child health
      policy.

PMID- 22999353
TI  - Pediatrics and the dollar sign: charges, costs, and striving towards value.

PMID- 22999354
TI  - Notes to a young investigator on how we might change the world.

PMID- 22999355
TI  - Home visitation by pediatric residents - perspectives from two pediatric training
      programs.

PMID- 22999356
TI  - Production of keratinolytic enzyme by an indigenous feather-degrading strain
      Bacillus cereus Wu2.
AB  - A novel feather-degrading microorganism was isolated from a poultry farm in
      Taiwan, and was identified Bacillus cereus Wu2 according to 16S rRNA sequencing.
      The isolated strain produces keratinolytic enzyme using chicken feather as the
      sole carbon and nitrogen source. The experimental results indicated that the
      extra carbon sources (glucose, fructose, starch, sucrose, or lactose) could act
      as a catabolite repressor to the enzyme secretion or keratinolytic activity when
      keratinous substrates were employed as protein sources. However, addition of 2
      g/L of NH(4)Cl to the feather medium increased the enzyme production. The optimum
      temperature and initial pH for enzyme production were 30 degrees C and 7.0,
      respectively. The maximum yield of the enzyme was 1.75 kU/mL in the optimal
      chicken feather medium; this value was about 17-fold higher than the yield in the
      basal hair medium. The B. cereus Wu2 possessed disulfide reductase activity along
      with keratinolytic activity. The amino acid contents of feathers degradated by B.
      cereus Wu2 were higher, especially for lysine, methionine and threonine which
      were nutritionally essential amino acids and usually deficient in the feather
      meal. Thus, B. cereus Wu2 could be not only used to enhance the nutritional value
      of feather meal but is also a potential bioinoculant in agricultural
      environments.

PMID- 22999357
TI  - Bioaugmentation of a wastewater bioreactor system with the nitrous oxide-reducing
      denitrifier Pseudomonas stutzeri strain TR2.
AB  - In bioaugmentation technology, survival of inoculant in the treatment system is
      prerequisite but remains to be a crucial hurdle. In this study, we bioaugmented
      the denitrification tank of a piggery wastewater treatment system with the
      denitrifying bacterium Pseudomonas stutzeri strain TR2 in two pilot-scale
      experiments, with the aim of reducing nitrous oxide (N(2)O), a gas of
      environmental concern. In the laboratory, strain TR2 grew well and survived with
      high concentrations of nitrite (5-10 mM) at a wide range of temperatures (28-40
      degrees C). In the first augmentation of the pilot-scale experiment, strain TR2
      inoculated into the denitrification tank with conditions (30 degrees C, ~0.1 mM
      nitrite) survived only 2-5 days. In contrast, in the second augmentation with
      conditions determined to be favorable for the growth of the bacterium in the
      laboratory (40-45 degrees C, 2-5 mM nitrite), strain TR2 survived longer than 32
      days. During the time when the presence of strain TR2 was confirmed by
      quantitative real-time PCR, N(2)O emission was maintained at a low level even
      under nitrite-accumulating conditions in the denitrification and nitrification
      tanks, which provided indirect evidence that strain TR2 can reduce N(2)O in the
      pilot-scale system. Our results documented the effective application of growth
      conditions favorable for strain TR2 determined in the laboratory to maintain
      growth and performance of this strain in the pilot-scale reactor system and the
      decrease of N(2)O emission as the consequence.

PMID- 22999358
TI  - Decreased hydrogen production leads to selective butanol production in co
      cultures of Clostridium thermocellum and Clostridium saccharoperbutylacetonicum
      strain N1-4.
AB  - When Clostridium thermocellum and Clostridium saccharoperbutylacetonicum strain
      N1-4 were co-cultured hydrogen production decreased and butanol was selectively
      produced with extremely low level of acetone. Since the high butanol production
      correlates with low hydrogen production, the molecular selection of hydrogenase
      gene activity is expected to yield strains exhibiting a higher butanol ratio.

PMID- 22999359
TI  - Foot care practice - the key to prevent diabetic foot ulcers in India.
AB  - BACKGROUND: The magnitude of diabetic foot ulcers (DFUs) and the amputation rates
      due to DFUs remain high even in developing and developed countries. Yet, the
      influence of knowledge, attitude, and practice (KAP) of diabetic foot care (DFC)
      on DFU incidence is not studied much. OBJECTIVE: To study causal relationship
      between knowledge, attitude and practice (KAP) on DFC between diabetic patients
      with and without DFUs; and the risk factors associated with DFUs. METHODS: A
      consecutive of 203 diabetic patients (103 with DFU and 100 without DFU) were
      included in the study. Their demographic details, medical history, and personal
      habits were recorded. KAP on DFC was assessed using a questionnaire. Responses
      were recorded, scored, and analyzed. RESULTS: Of the cohort, 67.5% were males,
      mean age: 59.9 +/- 11.4 years. Patients without DFU had good knowledge on DFC
      compared to those with DFU (86% versus 69.9%) (p<0.001). Incidence of DFU was 9%
      and 39.8% (p<0.001) among patients who practiced and not practiced DFC
      respectively. 88% patients with and without DFUs; showed favorable attitude
      toward adopting DFC. Risk factors - diabetic peripheral neuropathy, peripheral
      vascular disease, retinopathy, nephropathy, smoking, tobacco chewing and alcohol
      consumption were significantly (p<0.001) associated with DFUs. CONCLUSIONS: An
      inverse relationship between DFU and foot care knowledge as well as practice was
      observed. Apart from tight glycemic control, diabetic patients must be educated
      and motivated on proper foot care practice and life style modifications for
      preventing DFUs.

PMID- 22999368
TI  - Clinician compliance with laboratory regulations requiring submission of relevant
      clinical data: A one year retrospective analysis.
AB  - BACKGROUND: The College of American Pathologists (CAP) recognizes the need for
      clinical data in the interpretation of specimens submitted for histopathologic
      evaluation. Anecdotal evidence indicates that clinician compliance with requests
      for clinical history is variable. DESIGN: Quality assurance data from August 1,
      2010 to September 31, 2011 were searched for all cases listing no clinical
      history. Four consecutive weeks of surgical pathology request forms were also
      reviewed for the presence or absence of clinical history and its accuracy.
      RESULTS: 21,700 cases were accessioned in the study period and 1293 (5.9%)
      requisitions contained no clinical history. The four-week review documented that
      143 of 1698 (8.4%) requisitions had no clinical history and 12 cases contained
      incorrect history (0.7%). CONCLUSIONS: Between 5.9% and 8.4% of requisitions
      contain no clinical history. In 0.2% of cases, clinical history was incorrect.
      Compliance with the CAP policy for clinical history appears poor.

PMID- 22999369
TI  - Prognostic value of metabolic tumor burden from (18)F-FDG PET in surgical
      patients with non-small-cell lung cancer.
AB  - OBJECTIVE: To assess the prognostic value of metabolic tumor burden as measured
      with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on 2-deoxy-2
      ((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed
      tomography (CT), independent of current Union Internacional Contra la
      Cancrum/American Joint Committee on Cancer tumor, node, and metastasis (TNM)
      stage; in comparison with that of standardized uptake value (SUV) in surgical
      patients with non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: This
      study retrospectively reviewed 104 consecutive surgical patients (47 males, 57
      females, median age at PET/CT scan of 67.92 years) with diagnosed stage I to IV
      NSCLC who had baseline (18)F-FDG PET/CT scans. The (18)F-FDG PET/CT scans were
      performed in accordance with National Cancer Institute guidelines. The MTV of
      tumors in the whole body (MTV(WB)), TLG of tumors in the whole body (TLG(WB)),
      the maximum standardized uptake value of tumors in the whole body (SUV(maxWB)) as
      well as the mean standardized uptake value of tumor in the whole body
      (SUV(meanWB)) were measured. The median follow-up among 67 survivors was 42.07
      months from the PET/CT (range 2.82-80.95 months). Statistical methods included
      Kaplan-Meier curves, Cox regression, and C-statistics. The interobserver
      variability of SUV(maxWB), SUV(meanWB), MTV(WB), and TLG(WB) between two
      observers was analyzed using concordance correlation coefficients (CCCs).
      RESULTS: The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB) and
      TLG(WB) was very low with CCCs greater than 0.882. There was a statistically
      significant association of stage with overall survival (OS). The hazard ratio
      (HR) of stage III and stage IV as compared with stage I was 3.60 (P = .001) and
      4.00 (P = .013), respectively. The MTV(WB) was significantly associated with OS
      with a HR for 1-unit increase of ln(MTV(WB)) of 1.40/1.32 (P = .004/.039),
      before/after adjusting for stage and other prognostic factors including
      chemoradiation therapy, and surgical procedure, respectively. TLG(WB) had a
      statistically significant association with OS before and after adjusting for
      stage and the other prognostic factors. The HR for 1-unit increase in ln(TLG(WB))
      was 1.26 (P = .011) and 1.25 (P = .031), before and after the adjustment,
      respectively. Subjects with conditions that led to pneumonectomy (HR = 2.82, P =
      .035) or segmental resection (HR = 3.44, P = .044) had significantly worse
      survival than those needing lobectomy. There was no statistically significant
      association between OS and age, gender, tumor histology, ln(SUV(maxWB)), and
      ln(SUV(meanWB)) (all P > .05). There were 37 deaths during follow-up. CONCLUSION:
      Baseline whole-body metabolic tumor burden as measured with MTV(WB) and TLG(WB)
      on FDG PET is a prognostic measure independent of clinical stage and other
      prognostic factors including chemoradiation therapy and surgical procedure with
      low interobserver variability and may be used to further risk stratify surgical
      patients with NSCLC. This study also suggests that MTV and TLG are better
      prognostic measures than SUV(max) and SUV(mean). These results will need to be
      validated in larger cohorts in a prospective study.

PMID- 22999370
TI  - Are self-adhesive resin cements a valid alternative to conventional resin
      cements? A laboratory study of the long-term bond strength.
AB  - OBJECTIVES: The aim of the study was to test whether or not the shear bond
      strengths of six self-adhesive resin cements to dentin and to glass-ceramic, 24h
      and long-term-aged, are similar to the one of a conventional resin cement.
      METHODS: Human molars (N=168, n=12 per group) and silicabased glass-ceramic
      specimens (N=168, n=12 per group) were embedded in acrylic resin and randomly
      divided into 28 groups. The following resin cements were luted according to the
      manufacturers' instructions: Clearfil SA (CSA), G-Cem (GCM), SmartCem2 (SMC),
      SpeedCEM (SPC), RelyX Unicem (RXU), RelyX Unicem2 (RXU2) and Panavia21 (control
      group, PAN). Shear bond strength was measured initially (24h of water storage 37
      degrees C) and after aging (24,000 thermal cycles, 5/55 degrees C). The failure
      types (adhesive, and cohesive) were evaluated after debonding. The shear bond
      strength values were analyzed using three-way and one-way ANOVA, followed by a
      post hoc Scheffe and two-sample Student's t-tests. RESULTS: RXU, RXU2 and GCM
      showed similar after 24h and aged shear bond strength to dentin as the control
      group. CSA, SMC and SPC exhibited significantly lower values. Before aging, none
      of the bond strength values to glass-ceramic differed significantly from the
      other. After thermocycling, GCM showed higher results to glass-ceramic than CSA,
      SMC, RXU2 and the control group. Analyzing failure types after spontaneous
      debonding and shear bond test at dentin, solely adhesive failures were found,
      while at glass-ceramic only cohesive failures occurred. CONCLUSION: Not all self
      adhesive resin cements can be a valid alternative to conventional resin cements
      in order to bond silica-based glass-ceramics to human dentin.

PMID- 22999371
TI  - Should we be concerned about composite (nano-)dust?
AB  - Dental personnel often come into contact with composite dust upon polishing or
      grinding composites. Contemporary composites typically contain high amounts of
      (silica) nano-filler, but so far it has never been investigated whether composite
      dust may be hazardous. OBJECTIVES: The objectives of this study were (1) to
      characterize composite dust in vitro and (2) to assess the clinical exposure.
      METHODS: Polymerized blocks of contemporary composites were ground with a diamond
      bur according to a clinically relevant protocol, and aerosolized dust was
      collected on 1-MUm pore-size filters and gravimetrically quantified. In addition,
      the dust was characterized by transmission electron microscopy. Respirable dust
      was quantified with a mass particle counter in a dental operatory. RESULTS: All
      composites released respirable dust (<5MUm) in vitro. These observations were
      corroborated by the clinical measurements; however only short episodes of high
      concentrations of respirable dust upon polishing composites could be observed.
      Electron microscopic analysis showed that the size of the dust varied widely with
      particles larger than 10MUm, but submicron and even nano-sized particles could
      also be observed. The dust particles often consisted of multiple filler particles
      contained in resin, but single nano-filler particles could also frequently be
      distinguished. SIGNIFICANCE: This study showed that inhalation of composite dust
      is better avoided. Therefore, it is recommended to always use water-cooling upon
      polishing or removing composites, to use good aspiration, to frequently ventilate
      the dental operatory and to wear masks with high particle-filtration efficiency
      for small particle sizes.

PMID- 22999372
TI  - Ion concentration adjacent to glass-ionomer restorations in primary molars.
AB  - OBJECTIVES: The aim was to compare the levels of fluoride, calcium and phosphorus
      in enamel and dentin alongside glass-ionomer-based restorations over time.
      METHODS: This CCT consisted of children with cavities in the occlusal surface of
      primary molars that were restored with either a high-viscosity (Fuji IX GP((r)))
      or a resin-modified glass-ionomer (Vitremer((r))), being the test groups. Sound
      teeth (controls) were harvested from the children belonging to the test groups.
      Sampled teeth were cut in half and the ion concentration measured using EPMA.
      ANOVAs, and Newman-Keuls tests were performed to analyze the data. The study
      sample consisted of 35 children having 29 teeth per group available for analyses.
      RESULTS: Although statistically significantly higher, the mean ion-concentration
      of calcium in enamel and dentin, and that of phosphorous in dentin hardly
      differed between the tests and control groups. The mean fluoride concentration in
      enamel (0.20ppm*10(3) and 0.24ppm*10(3)) and dentin (0.71ppm*10(3) and
      0.78ppm*10(3)) surrounding the Fuji IX GP((r)) and Vitremer((r)) restored teeth,
      respectively was statistically significantly higher than in enamel
      (0.12ppm*10(3)) and dentin (0.12ppm*10(3)) for the control teeth. SIGNIFICANCE:
      The present in vivo investigation showed that fluoride ions are released from
      high-viscosity and resin-modified glass-ionomer primary restoration into the
      restorations' surrounding enamel and, and in particular, dentin.

PMID- 22999373
TI  - Influence of Y-TZP ceramic treatment and different resin cements on bond strength
      to dentin.
AB  - OBJECTIVES: Evaluating the bond strength (sigma) of resin cement systems (RXA -
      RelyX ARC; RXU - RelyX U100; and PF - Panavia F) to dentin and yttria-stabilized
      zirconia-based ceramic (YZ - In-Ceram YZ) after different surface treatments and
      aging. METHODS: Occlusal dentin of 54 human molars was exposed and conditioned
      following manufacturers' instructions. Fifty-four YZ blocks were sintered and
      divided into two groups according to surface treatment: PA - airborne particle
      abrasion, and SC - tribochemical silica coating. All treated YZ blocks were
      cemented to dentin using one of the cement systems (RXA, RXU, and PF) following
      manufacturers' recommendations, which includes specific silane agents. Teeth
      cement-ceramic blocks were stored in 37 degrees C distilled water for 24h before
      cutting into non-trimming bar-shaped specimens (adhesive area, A=1+/-0.1mm(2)).
      Specimens (n>=12) were assigned to one of the following conditions: N - no
      storage; W - stored in 37 degrees C distilled water for 60days; and TC - thermal
      cycling (5-55 degrees C; 10,000 cycles). All specimens were loaded in tension (F)
      to failure using a universal testing machine. The sigma (F/A) was calculated and
      data were statistically analyzed using ANOVA and Tukey tests (alpha=0.05).
      Fracture surfaces were examined to determine the failure mode. RESULTS: RXA-SC
      and PF-PA specimens showed the greatest mean sigma values after N (13.9 and
      13.0MPa, respectively) and TC (12.9 and 14.8MPa, respectively). SC-treated showed
      greater mean sigma values than PA-treated YZ specimens after W. SIGNIFICANCE:
      Regardless of the cement used, W and TC did not significantly reduce the sigma of
      SC-treated YZ resin bonded to dentin.

PMID- 22999374
TI  - Nanoindentation creep versus bulk compressive creep of dental resin-composites.
AB  - OBJECTIVES: To evaluate nanoindentation as an experimental tool for
      characterizing the viscoelastic time-dependent creep of resin-composites and to
      compare the resulting parameters with those obtained by bulk compressive creep.
      METHODS: Ten dental resin-composites: five conventional, three bulk-fill and two
      flowable were investigated using both nanoindentation creep and bulk compressive
      creep methods. For nano creep, disc specimens (15mm*2mm) were prepared from each
      material by first injecting the resin-composite paste into metallic molds.
      Specimens were irradiated from top and bottom surfaces in multiple overlapping
      points to ensure optimal polymerization using a visible light curing unit with
      output irradiance of 650mW/cm(2). Specimens then were mounted in 3cm diameter
      phenolic ring forms and embedded in a self-curing polystyrene resin. Following
      grinding and polishing, specimens were stored in distilled water at 37 degrees C
      for 24h. Using an Agilent Technologies XP nanoindenter equipped with a Berkovich
      diamond tip (100nm radius), the nano creep was measured at a maximum load of 10mN
      and the creep recovery was determined when each specimen was unloaded to 1mN. For
      bulk compressive creep, stainless steel split molds (4mm*6mm) were used to
      prepare cylindrical specimens which were thoroughly irradiated at 650mW/cm(2)
      from multiple directions and stored in distilled water at 37 degrees C for 24h.
      Specimens were loaded (20MPa) for 2h and unloaded for 2h. One-way ANOVA, Levene's
      test for homogeneity of variance and the Bonferroni post hoc test (all at
      p<=0.05), plus regression plots, were used for statistical analysis. RESULTS:
      Dependent on the type of resin-composite material and the loading/unloading
      parameters, nanoindentation creep ranged from 29.58nm to 90.99nm and permanent
      set ranged from 8.96nm to 30.65nm. Bulk compressive creep ranged from 0.47% to
      1.24% and permanent set ranged from 0.09% to 0.38%. There was a significant
      (p=0.001) strong positive non-linear correlation (r(2)=0.97) between bulk creep
      and nano creep that could also be expressed via a simple fractional-power
      function. A significant (p=0.003) positive linear correlation (r(2)=0.69) existed
      between nano creep recovery and bulk creep recovery. With both methods of
      examination, except for Venus Bulk FillTM (VB), the flowable and bulk-fill resin
      composites exhibited creep within the range exhibited by the conventional resin
      composites. SIGNIFICANCE: Despite the differences in loading and unloading
      conditions, in both methods of examination the correlation observed between the
      creep and recovery responses for a set of resin-composites was high. Both nano
      creep and recovery positively correlated with loading and unloading rates,
      respectively.

PMID- 22999375
TI  - [Epidemiological profile of late mortality in severe polytraumatisms].
AB  - OBJECTIVE: A study is made of the epidemiology, chronogramand causes of late
      mortality in traumatized patients. DESIGN: A prospective, observational cohort
      study of adult trauma patients was carried out. SETTINGS: Province of Guipuzcoa
      (Basque Country, Spain). Intensive care unit of a tertiary hospital. PATIENTS:
      Patients with severe trauma (Injury Severity Score > 15), admitted to the ICU
      from January 1995 to December 2009, with late death (> 7 days). VARIABLES:
      Epidemiological, laboratory test, hemodynamic and transfusional data were
      collected. Severity scores: Abbreviated Injury Scale (AIS) and ISS. RESULTS:
      Patients: 2003; ISS: 24.3+/-14.2. Total deaths: 405 (20%). Late mortality (>7
      days): 102 (25.2%) patients, 9 years older and with a lower (18 points) ISS score
      than the patients who died early (48 hours). Most frequent injuries: AIS-Head
      Cervical spine >= 4 (52%); AIS-Abdomen >= 4 (19.6%); AIS-Chest >= 4 (11.7%); AIS
      Extremities >= 4 (4.9%). Causes of death: 1) brain death (14.7%); 2) multiorgan
      failure (67.6%), in two injury contexts: a) severe brain trauma in the vegetative
      state and high spinal cord injuries with tetraplegia (35.3%); and b) non
      neurological injuries (32.3%) with a high prevalence of hypovolemic shock,
      multiple transfusion and coagulopathy; 3) miscellaneous (10.7%): post
      resuscitation anoxic-ischemic encephalopathy, pulmonary embolism and massive
      stroke; 4) non-evaluable (7%). CONCLUSIONS: Age, severity and type of injuries
      have an influence upon the time distribution and causality of late mortality.
      Brain death remains predominant, with multiorgan failure as the most frequent
      cause. This knowledge should contribute to the identification of problems, and to
      better organization of the structural and educational resources, thereby reducing
      the likely factors leading to death from trauma.

PMID- 22999376
TI  - The effect of contralateral pelvic drop and trunk lean on frontal plane knee
      biomechanics during single limb standing.
AB  - Pelvic drop as a result of hip abductor weakness has been hypothesized as a
      potential modifier of frontal plane knee joint kinetics during gait in
      individuals with pathology such as knee osteoarthritis (OA). However, hip muscle
      strengthening interventions have failed to find significant reductions in frontal
      plane loading measures such as the external knee adduction moment (KAM) with
      altered hip strength. Since this could in part be due to a lack of change in
      pelvic kinematics between conditions or test sessions or due to alterations in
      lateral trunk lean angle, the relationship between pelvic drop and subsequent
      changes in centre of mass with knee joint loading remains unclear. The purpose of
      this study was to examine the effect of a consciously altered frontal plane
      centre of mass position (pelvic drop and trunk lean to the contralateral side) on
      the KAM during single limb standing. Twenty healthy individuals performed a
      series of single limb standing trials, where they were asked to balance on their
      dominant leg. KAM was assessed during single limb stance in two conditions: with
      pelvis and trunk maintained in a level position, and with contralateral pelvic
      drop. A third condition involving contralateral pelvic drop and trunk lean was
      assessed to examine exaggerated changes in centre of mass. The KAM increased
      significantly with contralateral pelvic drop (p=0.001) and with combined
      contralateral pelvic drop and trunk lean (p<0.001) compared to the level pelvis
      trials. These findings suggest that pelvic drop alone can significantly increase
      KAM magnitude, a risk factor for the progression of knee OA. Assessment of pelvic
      obliquity prior to treatment may allow those with marked pelvic drop to be
      targeted for hip muscle strengthening.

PMID- 22999377
TI  - Predicting multiple step placements for human balance recovery tasks.
AB  - Stepping is one of the predominant strategies to restore balance against an
      external perturbation. Although models have been proposed to estimate the
      recovery step placement for a given perturbation, they suffer from major
      limitations (step execution time usually neglected, no more than a single step
      recovery considered, etc.). The purpose of this study is to overcome these
      limitations and to develop a simple balance recovery model which can predict a
      complete multiple step recovery response. Inspired by the field of walking
      robots, we adapted a control scheme formerly proposed for biped robot locomotion.
      The scheme relies on a Linear Model Predictive Controller (LMPC) which estimates
      the best foot placements to zero the velocity of the Center of Mass (CoM), i.e.
      to reach a steady posture. The predicted step placements were compared against
      previously reported experimental data for tether-release conditions. They match
      correctly for various perturbation levels and both single step or multiple steps
      recovery. Although the current model still suffers from limitations (e.g.,
      limited to the sagittal plane), these results demonstrate its ability to
      reproduce balance recovery reactions for different experimental scenarios.

PMID- 22999378
TI  - Rapidly relocating molecules between organelles to manipulate small GTPase
      activity.
AB  - Chemically inducible rapid manipulation of small GTPase activity has proven a
      powerful approach to dissect complex spatiotemporal signaling of these molecular
      switches. However, overexpression of these synthetic molecular probes freely in
      the cytosol often results in elevated background activity before chemical
      induction, which perturbs the cellular basal state and thereby limits their wide
      application. As a fundamental solution, we have rationally designed and newly
      developed a strategy to remove unwanted background activity without compromising
      the extent of induced activation. By exploiting interaction between a membrane
      lipid and its binding protein, target proteins were translocated from one
      organelle to another on a time scale of seconds. This improved strategy now
      allows for rapid manipulation of small GTPases under a physiological state, thus
      enabling fine dissection of sophisticated signaling processes shaped by these
      molecules.

PMID- 22999380
TI  - Contingency management is effective across cocaine-dependent outpatients with
      different socioeconomic status.
AB  - Contingency management (CM) has demonstrated its efficacy for treating cocaine
      dependence, but there is still some controversy with regard to its dissemination.
      Understanding how individual differences affect CM outcomes is important for
      detecting barriers to its dissemination. The aim of this study is to examine the
      impact of socioeconomic variables in cocaine-dependent outpatients on the
      effectiveness of CM in a community setting. Cocaine-dependent outpatients (N=118)
      were randomized to community reinforcement approach (CRA) treatment or a CRA plus
      vouchers program. The impact of baseline economic variables, alone and in
      combination with treatment conditions, on abstinence and retention outcomes after
      6 months of treatment was assessed. Results showed that income had no effect on
      retention or abstinence outcomes after 6 months of treatment in either treatment
      condition. The addition of a CM component was beneficial for individuals with any
      socioeconomic status. These results support the generalizability of CM strategies
      with patients of different socioeconomic status in community settings.

PMID- 22999379
TI  - Substance use and posttraumatic stress disorder symptoms in trauma center
      patients receiving mandated alcohol screening and brief intervention.
AB  - In an effort to integrate substance abuse treatment at trauma centers, the
      American College of Surgeons has mandated alcohol screening and brief
      intervention (SBI). Few investigations have assessed trauma center inpatients for
      comorbidities that may impact the effectiveness of SBI that exclusively focuses
      on alcohol. Randomly selected SBI eligible acute care medical inpatients (N=878)
      were evaluated for alcohol, illegal drugs, and symptoms consistent with a
      diagnosis of posttraumatic stress disorder (PTSD) using electronic medical
      record, toxicology, and self-report assessments; 79% of all patients had one or
      more alcohol, illegal drug, or PTSD symptom comorbidity. Over 70% of patients
      receiving alcohol SBI (n=166) demonstrated one or more illegal drug or PTSD
      symptom comorbidity. A majority of trauma center inpatients have comorbidities
      that may impact the effectiveness of mandated alcohol SBI. Investigations that
      realistically capture, account for, and intervene upon these common comorbid
      presentations are required to inform the iterative development of college policy
      targeting integrated substance abuse treatment at trauma centers.

PMID- 22999381
TI  - Safety network screening for municipalities with incomplete traffic volume data.
AB  - Safety network screening is used to identify road locations, such as
      intersections and roadway segments that exhibit an unusually high number of
      expected collisions or an abnormally high proportion of a certain configuration
      of collisions. Current state-of-the-art network screening methods rely on safety
      performance functions (SPFs) that require traffic volume as an input, but many
      cities in North America, including the city of Saskatoon, do not collect traffic
      volume for every intersection and segment within the city limits. Lack of traffic
      volume data severely restricts the applicability of a SPF-based network screening
      method. The binomial and beta-binomial tests, however, are formal collision
      diagnosis tests that can be used as a supplementary tool for screening roadway
      networks that include roadway segments for which traffic volume data are not
      available. However, previous studies have applied these two collision diagnosis
      tests without explicitly defining the particular circumstances that indicate
      which test is preferable. This study introduces a formal statistical test known
      as the "C(alpha) test" to determine when there is a need to apply the beta
      binomial test instead of the binomial test to screen a roadway network. The study
      targeted major arterial uncontrolled access segments in Saskatoon using five
      years (2005-2009) of collision data for the two most frequent collision
      configurations: (1) rear end, and (2) side swipe same direction collisions.
      ArcGIS was used to develop collision maps that visually display the screening
      results. The collision maps are designed to facilitate the governing agencies'
      decision-making processes when selecting appropriate safety countermeasures to
      reduce target collision configurations at screened locations.

PMID- 22999382
TI  - Mitigating the effects of in-vehicle distractions through use of the
      Psychological Refractory Period paradigm.
AB  - Modern driving involves frequent and potentially detrimental interactions with
      distracting in-vehicle tasks. Distraction has been shown to slow brake reaction
      time and decrease lateral and longitudinal vehicle control. It is likely that
      these negative effects will become more prevalent in the future as advances are
      made in the functionality, availability, and number of in-vehicle systems. This
      paper addresses this problem by considering ways to manage in-vehicle task
      presentation to mitigate their distracting effects. A driving simulator
      experiment using 48 participants was performed to investigate the existence of
      the Psychological Refractory Period in the driving context and its effect on
      braking performance. Drivers were exposed to lead vehicle braking events in
      isolation (single-task) and with a preceding surrogate in-vehicle task (dual
      task). In dual-task scenarios, the time interval between the in-vehicle and
      braking tasks was manipulated. Brake reaction time increased when drivers were
      distracted. The in-vehicle task interfered with the performance of the braking
      task in a manner that was dependent on the interval between the two tasks, with
      slower reactions following a shorter inter-task interval. This is the
      Psychological Refractory Period effect. These results have implications for
      driver safety during in-vehicle distraction. The findings are used to develop
      recommendations regarding the timing of in-vehicle task presentation so as to
      reduce their potentially damaging effects on braking performance. In future,
      these guidelines could be incorporated into a driver workload management system
      to minimise the opportunity for a driver to be distracted from the ongoing
      driving task.

PMID- 22999383
TI  - Dynamic regulation of Polycomb group activity during plant development.
AB  - Polycomb group (PcG) complexes play important roles in phase transitions and cell
      fate determination in plants and animals, by epigenetically repressing sets of
      genes that promote either proliferation or differentiation. The continuous
      differentiation of new organs in plants, such as leaves or flowers, requires a
      highly dynamic PcG function, which can be induced, modulated, or repressed when
      necessary. In this review, we discuss the recent advance in understanding PcG
      function in plants and focus on the diverse molecular mechanisms that have been
      described to regulate and counteract PcG activity in Arabidopsis.

PMID- 22999384
TI  - High-pressure injection injuries.

PMID- 22999385
TI  - Anamnestic immunological response profile in laboratory animals after
      immunization with recombinant hepatitis B vaccines of different generations.
AB  - Hepatitis B vaccines containing preS1 and preS2 fragments are assumed to be more
      immunogenic than those containing SHBs protein alone, which may be of importance
      for immunization of people with poorly induced or without any immunological
      response after vaccination. The aim of this study was to evaluate: The following
      conclusions can be drawn on the basis of obtained results:

PMID- 22999386
TI  - An European Organisation for Research and Treatment of Cancer phase I study of
      lapatinib and docetaxel as neoadjuvant treatment for human epidermal growth
      factor receptor 2 (HER2) positive locally-advanced/inflammatory or large operable
      breast cancer.
AB  - BACKGROUND: Lapatinib is an effective anti-HER2 therapy in advanced breast cancer
      and docetaxel is one of the most active agents in breast cancer. Combining these
      agents in pre-treated patients with metastatic disease had previously proved
      challenging, so the primary objective of this study aimed to determine the
      maximum tolerated dose (MTD) in treatment-naive patients, by identifying acute
      dose-limiting toxicities (DLT) during cycle 1 in the first part of a phases 1-2
      neoadjuvant European Organisation for Research and Treatment of Cancer (EORTC)
      trial. PATIENTS AND METHODS: Patients with large operable or locally-advanced
      HER2 positive breast cancer were treated with continuous lapatinib, and docetaxel
      every 21days for 4 cycles. Dose levels (DLs) were: 1000/75, 1250/75, 1000/85,
      1250/85, 1000/100 and 1250/100 (mg/day)/(mg/m(2)). RESULTS: Twenty-one patients
      were included. Two DLTs occurred at dose level 5 (1000/100); one grade 4
      neutropenia >= 7days and one febrile neutropenia. A further 3 patients were
      therefore treated at the same dose with prophylactic granulocyte-colony
      stimulating factor (G-CSF), and 3 patients at dose level 6. No further DLTs were
      observed. CONCLUSIONS: Our recommended dose for phase II is lapatinib 1000mg/day
      and docetaxel 100mg/m(2) with G-CSF in HER2 positive non-metastatic breast
      cancer. The dose of lapatinib should have been 1250mg/day but we were mindful of
      the high rate of treatment discontinuation in GeparQuinto with lapatinib
      1250mg/day combined with docetaxel. No grade 3-4 diarrhoea was observed.
      Pharmacodynamics analysis suggests that concomitant medications altering P
      glycoprotein activity (in addition to lapatinib) can modify toxicity, including
      non-haematological toxicities. This needs verification in larger trials, where it
      may contribute to understanding the sources of variability in clinical toxicity
      and treatment discontinuation.

PMID- 22999387
TI  - MiR-296-3p regulates cell growth and multi-drug resistance of human glioblastoma
      by targeting ether-a-go-go (EAG1).
AB  - MicroRNAs (miRNAs) - short non-coding RNA molecules - post-transcriptionally
      regulate gene expressions and play crucial roles in diverse biological processes
      such as development, differentiation, apoptosis and proliferation. In order to
      investigate the possible role of miRNAs in the development of multi-drug
      resistance (MDR) in human glioblastoma, we first detected (by Western blotting,
      real-time polymerase chain reaction [RT-PCR] and immunohistochemistry) the
      expression of miR-296-3p and ether-a-go-go (EAG1 or KCNH1) in U251 cells,
      U251/imatinib mesylate (U251AR cells) and clinical specimens. The results showed
      that miR-296-3p was down-regulated in U251AR cells, concurrent with the up
      regulation of EAG1 protein, compared with the parental U251 cell line. In vitro
      drug sensitivity assay demonstrated that over-expression of miR-296-3p sensitised
      glioblastoma (GBM) cells to anticancer drugs, whereas down-expression using
      antisense oligonucleotides conferred MDR. Ectopic expression of miR-296-3p
      reduced EAG1 expression and suppressed cell proliferation drug resistance, and
      the luciferase activity of an EAG1 3'-untranslated region-based reporter
      construct in U251AR cells, whereas EAG1 over-expression rescued the suppressive
      effect of miR-296-3p in U251AR cells. We also found that EAG1 was widely over
      expressed and inversely correlated with miR-296-3p in clinical specimens. Taken
      together, our findings suggest that miR-296-3p may play a role of MDR in
      glioblastoma at least in part by targeting EAG1.

PMID- 22999391
TI  - Dynamics of muscle activation during tonic-clonic seizures.
AB  - The purpose of our study was to elucidate the dynamics of muscle activation
      during generalised tonic-clonic seizures (GTCS). We recorded surface
      electromyography (EMG) from the deltoid muscle during 26 GTCS from 13 patients
      and compared it with GTCS-like events acted by 10 control subjects. GTCS
      consisted of a sequence of phases best described quantitatively by dynamics of
      the low frequency (LF) wavelet component (2-8Hz). Contrary to the traditional
      view, the tonic phase started with a gradual increase in muscle activity. A
      longer clonic phase was associated with a shorter onset of the tonic phase and a
      higher seizure occurrence. Increase in LF occurred during the onset phase and
      during the transition from the tonic to the clonic phase, corresponding to the
      vibratory movements. The clonic phase consisted of EMG discharges of remarkably
      constant duration (0.2s) separated by silent periods (SP) of exponentially
      increasing duration - features that could not be reproduced voluntarily. The last
      SP was longer in seizures with higher EMG peak frequency whereas the energy of
      the last clonus was higher in seizures with a short clonic phase. We found
      specific features of muscle activation dynamics during GTCS. Our findings suggest
      that the same inhibitory mechanisms that contribute to GTCS termination
      counteract seizure initiation, accounting for the gradual onset. Both active
      inhibition and mechanisms related to metabolic depletion act synergistically to
      stop the seizure. Analysis of the ictal EMG dynamics is a valuable tool for
      monitoring the balance between pro-convulsive and anti-convulsive factors.

PMID- 22999388
TI  - A role of ghrelin in canine mammary carcinoma cells proliferation, apoptosis and
      migration.
AB  - BACKGROUND: Ghrelin is a natural ligand of the growth hormone secretagogue
      receptor (GHS-R). They are often co-expressed in multiple human tumors and
      related cancer cell lines what can indicate that the ghrelin/GHS-R axis may have
      an important role in tumor growth and progression. However, a role of ghrelin in
      canine tumors remains unknown. Thus, the aim of our study was two-fold: (1) to
      assess expression of ghrelin and its receptor in canine mammary cancer and (2) to
      examine the effect of ghrelin on carcinoma cells proliferation, apoptosis,
      migration and invasion. The expression of ghrelin and its receptor in canine
      mammary cancer tissues and cell lines (isolated from primary tumors and their
      metastases) was examined using Real-time qPCR and immunohistochemistry. For
      apoptosis analysis the Annexin V and propidium iodide dual staining was applied
      whereas cell proliferation was evaluated by MTT assay and BrdU incorporation
      test. The influence of ghrelin on cancer cells migration and invasion was
      assessed using Boyden chamber assays and wound healing assay. RESULTS: The
      highest expression of ghrelin was observed in metastatic cancers whereas the
      lowest expression of ghrelin receptor was detected in tumors of the 3rd grade of
      malignancy. Higher expression of ghrelin and its receptor was detected in cancer
      cell lines isolated from metastases than in cell lines isolated from primary
      tumors. In vitro experiments demonstrated that exposure to low doses of ghrelin
      stimulates cellular proliferation, inhibits apoptosis and promotes motility and
      invasion of canine mammary cancer cells. Growth hormone secretagogue receptor
      inhibitor ([D-Lys3]-GHRP6) as well as RNA interference enhances early apoptosis.
      CONCLUSION: The presence of ghrelin and GHS-R in all of the examined canine
      mammary tumors may indicate their biological role in cancer growth and
      development. Our experiments conducted in vitro confirmed that ghrelin promotes
      cancer development and metastasis.

PMID- 22999392
TI  - Ground reaction forces in shallow water running are affected by immersion level,
      running speed and gender.
AB  - OBJECTIVES: To analyze the effect of depth of immersion, running speed and gender
      on ground reaction forces during water running. DESIGN: Controlled laboratory
      study. METHODS: Twenty adults (ten male and ten female) participated by running
      at two levels of immersion (hip and chest) and two speed conditions (slow and
      fast). Data were collected using an underwater force platform. The following
      variables were analyzed: vertical force peak (Fy), loading rate (LR) and anterior
      force peak (Fx anterior). Three-factor mixed ANOVA was used to analyze data.
      RESULTS: Significant effects of immersion level, speed and gender on Fy were
      observed, without interaction between factors. Fy was greater when females ran
      fast at the hip level. There was a significant increase in LR with a reduction in
      the level of immersion regardless of the speed and gender. No effect of speed or
      gender on LR was observed. Regarding Fx anterior, significant interaction between
      speed and immersion level was found: in the slow condition, participants
      presented greater values at chest immersion, whereas, during the fast running
      condition, greater values were observed at hip level. The effect of gender was
      only significant during fast water running, with Fx anterior being greater in the
      men group. Increasing speed raised Fx anterior significantly irrespective of the
      level of immersion and gender. CONCLUSIONS: The magnitude of ground reaction
      forces during shallow water running are affected by immersion level, running
      speed and gender and, for this reason, these factors should be taken into account
      during exercise prescription.

PMID- 22999393
TI  - Effects of low-load resistance training combined with blood flow restriction or
      hypoxia on muscle function and performance in netball athletes.
AB  - OBJECTIVES: To investigate the effect of blood flow restriction or normobaric
      hypoxic exposure combined with low-load resistant exercise (LRE), on muscular
      strength and endurance. DESIGN: A randomised controlled trial. METHODS: Well
      trained netball players (n=30) took part in a 5 weeks training of knee flexor and
      extensor muscles in which LRE (20% of one repetition maximum) was combined with
      (1) an occlusion pressure of approximately 230mmHg around the upper thigh (KT,
      n=10), (2) hypoxic air to generate blood oxyhaemoglobin levels of approximately
      80% (HT, n=10) or (3) with no additional stimulus (CT, n=10). The training was of
      the same intensity and amount in all groups. One to five days before and after
      training, participants performed a series of strength and endurance tests of the
      lower limbs (3-s maximal voluntary contraction [MVC3], area under 30-s force
      curve [MVC30], number of repetitions at 20% 1RM [Reps201RM]). In addition, the
      cross-sectional area (CSA) of the quadriceps and hamstrings were measured.
      RESULTS: Relative to CT, KT and HT increased MVC3 (11.0+/-11.9% and 15.0+/
      13.1%), MVC30 (10.2+/-9.0% and 18.3+/-17.4%) and Reps201RM (28.9+/-23.7% and
      23.3+/-24.0%, mean+/-90% confidence interval) after training. CSA increased by
      6.6+/-4.5%, 6.1+/-5.1% and 2.9+/-2.7% in the KT, HT and CT groups respectively.
      CONCLUSIONS: LRE in conjunction with KT or HT can provide substantial
      improvements in muscle strength and endurance and may be useful alternatives to
      traditional training practices.

PMID- 22999394
TI  - Pain management at inpatient wards of a university hospital.
AB  - BACKGROUND AND OBJECTIVES: This is an exploratory, descriptive and transversal
      study aiming to determine the prevalence, characterization, location, and
      measurement and discuss pharmacological analgesic measures for acute pain
      management in five inpatient wards of a university hospital. METHOD: We enrolled
      856 subjects in the study, of whom 272 were in pain at the time. Information
      related to pain was obtained using a bedside structured interview. Numeric pain
      scale and body diagram were used. RESULTS: Analgesia was assessed through medical
      records. The overall prevalence of pain was 31.8%, with severe pain in 44.2% and
      mean of 6.6 on numeric pain scale. The main reason was trauma and the most common
      site the abdomen. The most widely used analgesic was dipyrone (76.1%)
      with/without combination. Strong opioid was prescribed to 4.4%. For 27.5% there
      was no improvement. CONCLUSION: We conclude that pain is highly prevalent, poorly
      evaluated, undertreated, with inappropriate use of analgesics.

PMID- 22999395
TI  - Epidemiological and occupational profile of anesthesiologists practicing in Belo
      Horizonte, Minas Gerais--Brazil, in 2010.
AB  - BACKGROUND AND OBJECTIVES: Exposed to many occupational risk factors, the
      anesthesiologist should know how to experience situations related to work and
      everyday life, so that illness is not part of his reality. Knowledge of work
      through the worker himself is one way to look deeper into the universe
      surrounding health professionals in order to seek effective solutions that
      increase satisfaction and minimize damage. The objective of this paper was to
      outline an epidemiological and occupational profile of the anesthesiologist in
      Belo Horizonte, Minas Gerais. METHODS: Quantitative, cross-sectional randomized
      study conducted among members of the Society of Anesthesiology of Minas Gerais.
      Data collected through a questionnaire, including the CAGE, for evaluation of
      alcoholism and Self-Report Questionnaire (SRQ-20) to evaluate the prevalence of
      common mental disorders (CMD). RESULTS: There was predominance of male (62.4%)
      working on-call schedule (91.1%), both day and at night. The average number of
      night shifts was 5.4% in the last 30 days. Most of them (88.3%) working in
      emergency departments. Most professionals reported being very tired and
      overloaded or very overloaded, but satisfied with the work. There was statistical
      association between CAGE positive and work overload and between CAGE and SRQ-20.
      CONCLUSIONS: The population studied indicates that the anesthesiologist is a
      professional rather overloaded, which corroborates trends seen in the medical
      field. Major attention should be given to these professionals who live surrounded
      by harmful occupational hazards.

PMID- 22999396
TI  - Effects of preoperative sublingual misoprostol on uterine tone during isoflurane
      anesthesia for cesarean section.
AB  - BACKGROUND AND OBJECTIVES: Misoprostol would reduce the uterine bleeding after
      cesarean delivery without harmful effects on either mother or baby. We aimed to
      evaluate the effects of preoperative misoprostol on maternal blood loss, uterine
      tone, and the need for additional oxytocin after cesarean delivery under
      isoflurane anesthesia. METHODS: After ethical approval, 366 patients scheduled
      for elective cesarean delivery were randomly allocated to receive either
      sublingual misoprostol 400MUg (n=179) or placebo tablet (n=187) after intubation.
      Anesthesia was maintained with 0.5-0.7 MAC isoflurane with nitrous oxide. All
      patients received intravenous infusion of 10IU of oxytocin after placental
      delivery. Perioperative estimated blood loss, uterine tone, need for
      supplementary oxytocin, hematocrit, Apgar scores at 1 and 5 min and adverse
      effects were recorded. RESULTS: After induction, patients receiving sublingual
      misoprostol had significant less perioperative estimated blood loss (202+/-383.1
      vs. 708+/-204.3mL, p<0.001), need for oxytocin (p<0.001), higher hematocrit
      levels (p<0.001) and uterine tone (p<0.02). The incidence of shivering was higher
      in the misoprostol group (p=0.04). There were no differences between the two
      groups as regarding Apgar scores, nausea and vomiting, gastrointestinal
      disturbances and pyrexia. CONCLUSION: Preoperative administration of sublingual
      misoprostol 400MUg is safe and effective in attenuating the maternal bleeding and
      uterine atony from isoflurane anesthesia for cesarean delivery.

PMID- 22999397
TI  - Transesophageal echocardiography in anesthesiology: characterization of use
      profile in a tertiary hospital.
AB  - BACKGROUND AND OBJECTIVE: Since its introduction in the 80s, transesophageal
      echocardiography (TEE) not only gained popularity but also experienced great
      advances in technology and currently it is an extremely valuable tool in the
      intraoperative period. In Brazil, there are no published data on the profile of
      its use in the intraoperative period by anesthesiologists. The objective of this
      study was to describe the use of intraoperative TEE in an Anesthesiology Service
      in a tertiary private hospital. PATIENTS AND METHODS: Retrospective study from
      completed medical charts in all cases where the patient was monitored with TEE.
      Monitoring was applied in patients classified as I-II according to the American
      Society of Echocardiography and presenting no contraindication to the
      examination. At the end of procedure, after examination, a note on the chart
      classified monitoring according to its usefulness in the intraoperative period
      into three groups: group 1, no interference of TEE in anesthetic or surgical
      approach; group 2, TEE prompted change in anesthetic approach regarding the
      administration of volume, introduction and/or modification of vasoactive drugs
      (here, TEE generated change of anesthetic approach in conjunction with other
      monitors, but it was the deciding factor); group 3, TEE led to a change in
      approach or review of surgical procedure performed. RESULTS: From January 2009 to
      January 2011, 164 intraoperative TEE were performed in our service, with 41
      pediatric and 123 adult patients. In all patients, the test was successful and
      there were no problems regarding the introduction of transesophageal tube. In
      pediatric sample, group I had 10 patients (24.4%), group II had 27 patients
      (65.8%), and group III had 4 patients (9.8%). Among adults, group I had 38
      patients (30.9%), group II had 81 patients (65.9%), and group III had 4 patients
      (3.2%). CONCLUSION: Despite this small sample size compared to the literature,
      and the limitations of this study, there was agreement with other reports related
      to changes in anesthetic-surgical approach based on intraoperative TEE. Our data
      also strongly suggest that transesophageal echocardiography is an extremely
      useful tool for monitoring patients at high cardiovascular risk, even when
      undergoing noncardiac surgery. Larger studies conducted in our country are
      needed, as there are no other studies in literature defining the use profile of
      TEE or even clearly setting out how it has been used in our field.

PMID- 22999398
TI  - Reducing the concentration to 0.4% enantiomeric excess hyperbaric levobupivacaine
      (s75: r25) provides unilateral spinal anesthesia. Study with different volumes.
AB  - BACKGROUND AND OBJECTIVES: Unilateral spinal anesthesia may be obtained with
      hypobaric or hyperbaric solution. The objective of this study was to compare
      different doses of enantiomeric excess hyperbaric levobupivacaine to achieve
      unilateral spinal anesthesia. METHOD: One hundred and twenty patients were
      randomized to receive 4 mg, 6 mg or 8 mg of 0.4% enantiomeric excess
      levobupivacaine. The solutions were administered at the L3-L4, with the patient
      in a lateral position and kept at this position according to dose administration
      for 5, 10 or 15 minutes. Sensory block (pinprick) and motor block (scale 0-3)
      were compared between the operated and contralateral sides. RESULTS: The onset of
      analgesia was rapid and comparable between groups. Sensory block was
      significantly higher in the operated than in nonoperated limb at all times of
      evaluation. Increasing the dose by 1 mL (2mg) corresponded to an increase of two
      segments in the mode for the operated side. In the operated side, motor block (MB
      = 3) of patients occurred in 31 (77.5%) with 4 mg, 38 (95%) with 6 mg, and 40
      (100%) with 8 mg. There was a positive correlation between increased dose,
      blockade duration, and hypotension. All patients were satisfied with the
      technique used. CONCLUSIONS: Spinal anesthesia with different volumes of
      enantiomeric excess hyperbaric bupivacaine (S75: R25) provided a 78% incidence of
      unilateral spinal block, with the smallest dose used (4 mg) the most efficient.

PMID- 22999399
TI  - Analgesic efficacy of the intra-articular administration of S(+)- ketamine in
      patients undergoing total knee arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: Total knee arthroplasty (TKA) is associated with
      significant postoperative pain. Many intra-articular (IA) agents have been used
      for postoperative analgesia with inconsistent outcomes. Ketamine's enantiomer
      S(+), S(+)- ketamine, was recently introduced commercially, with higher analgesic
      potency and less side effects than the racemic form. An experimental prospective
      randomized double-blind study was conducted to evaluate the analgesic efficacy of
      intra-articular S(+)- ketamine in patients undergoing primary TKA. METHOD: In
      total, 56 patients were evaluated and allocated into three groups: Group A (n=19)
      received 0.25mg.kg(-1) of S(+)- ketamine diluted in 20mL of saline solution 0.9%;
      Group B (n=17) received 0.5mg.kg(-1) of S(+)- ketamine diluted in the same way;
      and Group C (n=20) received only 20mL of intra-articular saline 0.9%, immediately
      after surgery and drain placement. All patients had access to rescue analgesic
      therapy, with the use of intravenous morphine alone. Evaluations were made 2, 6,
      12, and 24 hours postoperatively, with measurement of pain intensity by Visual
      Analogue Scale (VAS), use of rescue medication by the evaluation of the time
      elapsed between the intra-articular injection of the solution and first dose of
      rescue, total consumption within 24 hours, and adverse effects. RESULTS: The S(+)
      ketamine groups had lower pain scores compared with the saline group. The lowest
      dose of intra-articular S(+)- ketamine (Group A: 0.25mg.kg(-1)) resulted in
      better pain scores and less rescue analgesia, with longer time to first request.
      Adverse effects were infrequent. The results with lower pain scores in groups
      using S(+)- ketamine are a trend, as there was no statistical significance
      between groups. CONCLUSION: In this study, with this sample, the analgesic effect
      of IA S(+)- ketamine was not superior to saline solution in the postoperative
      period of TKA.

PMID- 22999400
TI  - Incidence of shivering after cesarean section under spinal anesthesia with or
      without intrathecal sufentanil: a randomized study.
AB  - BACKGROUND AND OBJECTIVES: Shivering is a cause of discomfort and dissatisfaction
      in patients undergoing cesarean section. The objective of this study paper was to
      assess the impact of intrathecal administration of sufentanil on the incidence of
      shivering after cesarean section. METHOD: In a prospective blinded, randomized
      clinical trial, pregnant women undergoing cesarean section under spinal
      anesthesia were enrolled. Pregnant women in labor, febrile, obese, with pregnancy
      induced hypertension, anesthetic block failure or surgical complications were
      excluded. Patients were randomly assigned to two groups. In Group I, 10mg of 0.5%
      hyperbaric bupivacaine combined with 80 mcg of morphine and 2.5 mcg of sufentanil
      were administered. In Group II, 10mg of 0.5% hyperbaric bupivacaine combined with
      80 mcg of morphine were administered. In the post-anesthesia care unit, patients
      were evaluated for signs of shivering by an investigator blinded to the patient's
      group allocation. RESULTS: The sample consisted of 80 patients. In both groups
      there was a decrease in axillary temperature of patients after cesarean section
      (p<0.001). This decrease was not different between groups (p<0.21). In Group I,
      the incidence of tremor was 32.5% (13/40) and in Group II it was 62.5% (25/40)
      (p<0.007); RR 0.53 (CI 95% 0.32-0.87). CONCLUSIONS: It has been suggested that
      the addition of sufentanil to hyperbaric bupivacaine and morphine during spinal
      anesthesia for cesarean section provides a decrease in the incidence of shivering
      in the immediate postoperative period.

PMID- 22999401
TI  - Lipid therapy with two agents in ropivacaine-induced toxicity: experimental study
      in Swine.
AB  - BACKGROUND AND OBJECTIVE: Compare hemodynamic changes after ropivacaine-induced
      toxicity followed by treatment with two lipid emulsions in swine. METHODS: Large
      White pigs were anesthetized with thiopental, followed by intubation, and kept on
      mechanical ventilation. Hemodynamic variables at rest were recorded with invasive
      pressure monitoring and pulmonary artery catheterization. After 30 minutes,
      7mg.kg(-1) ropivacaine were injected intravenously and new hemodynamic
      measurements were performed within one minute. The animals were then randomly
      allocated into three groups and received: 4mL.kg(-1) saline solution, or 4mL.kg(
      1) lipid emulsion with long-chain triglycerides, or 4mL.kg(-1) lipid emulsion
      with longand medium-chain triglycerides. Hemodynamic changes were reevaluated at
      5, 10, 15, 20 and 30 minutes. RESULTS: Ropivacaine-induced toxicity mainly caused
      a drop in blood pressure and cardiac index without significant changes in
      vascular resistance. Therapy with lipid emulsions restored blood pressure
      primarily through increased vascular resistance, as cardiac index showed no
      significant improvement. Lipid emulsion with medium-chain triglycerides caused a
      greater increase in vascular resistance, particularly pulmonary. CONCLUSION: In
      groups receiving lipid emulsions, hemodynamic results were better than in control
      group. There were no differences in systemic arterial pressure and cardiac index
      between animals receiving lipid emulsion with long-chain triglycerides and mixed
      long- and medium-chain triglycerides.

PMID- 22999402
TI  - Influence of pleural drain insertion in lung function of patients undergoing
      coronary artery bypass grafting.
AB  - BACKGROUND AND OBJECTIVES: Longitudinal, prospective, randomized, blinded Trial
      to assess the influence of pleural drain (non-toxic PVC) site of insertion on
      lung function and postoperative pain of patients undergoing coronary artery
      bypass grafting in the first three days post-surgery and immediately after chest
      tube removal. METHOD: Thirty six patients scheduled for elective myocardial
      revascularization with cardiopulmonary bypass (CPB) were randomly allocated into
      two groups: SX group (subxiphoid) and IC group (intercostal drain). Spirometry,
      arterial blood gases, and pain tests were recorded. RESULTS: Thirty one patients
      were selected, 16 in SX group and 15 in IC group. Postoperative (PO) spirometric
      values were higher in SX than in IC group (p<0.05), showing less influence of
      pleural drain location on breathing. PaO(2) on the second PO increased
      significantly in SX group compared with IC group (p<0.0188). The intensity of
      pain before and after spirometry was lower in SX group than in IC group
      (p<0.005). Spirometric values were significantly increased in both groups after
      chest tube removal. CONCLUSION: Drain with insertion in the subxiphoid region
      causes less change in lung function and discomfort, allowing better recovery of
      respiratory parameters.

PMID- 22999403
TI  - Opioids and the immune system: clinical relevance.
AB  - BACKGROUND AND OBJECTIVES: The increasing use of opioids for pain treatment is a
      reality in several countries and, therefore, unusual questions arise, such as the
      influence of opioids on immune responses. The present study aims to detail the
      immune response by exploring the influences of opiate effects on inflammatory
      response in experimental and clinical situations, as well as its importance in
      daily practice. CONTENT: After reviewing the articles published in journals
      indexed in Medline, we found that immune response has been generally described,
      especially regarding its cellular aspect. Following this approach, we identified
      the mechanisms of endogenous opioid release, modulation of immune response to
      exogenous opioids in acute and chronic pain, always ending with the clinical
      implications and applicability in routine care. CONCLUSIONS: Although several
      studies point to an immunosuppressive effect of opioids, the clinical relevance
      of these observations remains uncertain and only serves as a prerequisite for
      further investigations in this area. Definitive recommendations for the use of
      opioids in various situations of clinical practice regarding the immunological
      consequences of these drugs still cannot be provided until the present moment.

PMID- 22999404
TI  - Regional analgesia in intensive care.
AB  - JUSTIFICATIONS AND OBJECTIVES: regional analgesia plays an important role in
      multimodal pain management in critically ill patients, minimizing patient
      discomfort and reducing the associated physiological and psychological stress.
      Lower doses of systemic opioids reduce some of its side effects, such as
      withdrawal syndrome, possible psychological changes, and gastrointestinal
      dysfunction. Despite these benefits, its use is controversial, as patients in
      intensive care units often have contraindications, such as coagulopathy,
      hemodynamic instability, and difficulty in neurological assessment and
      implementation of regional technique. CONTENT: The authors present a review of
      regional analgesia in intensive care, focusing on the main advantages and
      limitations of its use in critically ill patients, and describe the most commonly
      used regional techniques and its applicability.

PMID- 22999405
TI  - Retropharyngeal hematoma secondary to minor blunt neck trauma: case report.
AB  - BACKGROUND AND OBJECTIVES: The development of a retropharyngeal hematoma
      following a blunt trauma is a rare occurrence. However, a space-occupying lesion
      in this area can be life-threatening and requires rapid assessment and treatment.
      This is clinically important because of the close proximity of the
      retropharyngeal space to the upper airway. Any swelling in the the posterior
      pharyngeal space may prompt it to bulge anteriorly into the airway and cause its
      obstruction. CASE REPORT: A 86-year-old woman fell from a height of 1.5m and hit
      her neck on stairs and was admitted to our trauma department. A computerized
      tomography scan and a lateral neck x-ray to observe the soft tissue revealed a
      large retropharyngeal mass extending from the base of the skull down to the level
      of the lung. The patient was kept under observation and the hematoma reduced
      spontaneously in the following seven days although the patient died on the tenth
      day from pulmonary infection. The report emphasizes that early drainage of a
      retropharyngeal hematoma should be considered in similar cases. Although rarely
      encountered, retropharyngeal hematoma is a problem that can be faced in an
      emergency department.

PMID- 22999406
TI  - Airtraq(r) optical laryngoscope for tracheal intubation in a patient with giant
      lipoma at the nape: a case report.
AB  - BACKGROUND AND OBJECTIVES: Lipoma is a progressively increasing disease which may
      appear anywhere in the body. Its appearance at the back of the neck, especially
      when it is large enough to cause restriction of neck extension, poses challenges
      to anesthesiologists in airway management whenever needed. This paper evaluates
      the role of Airtraq(r) in restricted neck movement. CASE REPORT: Case with a huge
      lipoma of 14*12cm at the nape, and its surgical removal during an elective
      operation theatre posed difficulty in securing the airway by conventional
      laryngoscopy. To overcome the problem we successfully used a newly developed
      device, the Airtraq(r), which is an optical laryngoscope for securing the airway.
      CONCLUSION: Airtraq(r) can be used for elective intubation in patients with
      restricted neck movements.

PMID- 22999407
TI  - Pneumothorax post brachial plexus block guided by ultrasound: a case report.
AB  - BACKGROUND AND OBJECTIVES: Brachial plexus block is used for upper limbs
      anesthesia. The use of ultrasound-guided (USG) technique for blockade has become
      popular in recent years, facilitating its execution by providing real-time images
      of the plexus and surrounding structures while minimizing complications. The
      purpose of this report is to describe a case of pneumothorax following ultrasound
      guided interscalene block. CASE REPORT: Male patient, 49 years old, weight 62kg
      and height 1.72m, slender, smoker, asymptomatic, ASA II E. The patient underwent
      surgical repair of right ulna open fracture through USG-guided interscalene
      brachial plexus block with axillary supplementation. After sedation and
      antisepsis, the linear probe of the USG apparatus was placed perpendicular to the
      interscalene groove (12 Hz), and stimucath A50 introduced in plane. After
      visualization of nerve trunks, 20mL of ropivacaine 0.5% was administered with
      axillary block supplementation (same volume and concentration of anesthetic). At
      the end of surgery, the patient complained of respiratory-dependent chest pain
      associated with dyspnea and decreased pulse oximetry (91% in room air), but
      hemodynamic stable (BP=130/70 and HR=84 bpm). Although pulmonary auscultation was
      normal, chest X-ray showed the presence of right pneumothorax. Water seal chest
      drainage was performed, after which the patient reported improvement of symptoms
      and was discharged from hospital in good general condition after 8 days.
      CONCLUSION: Despite the dynamic visualization of cervical structures with USG,
      interscalene block may result in pneumothorax. An unusual higher pleural dome due
      to the hyperinflated lung (smoking) probably facilitated the accidental pleural
      puncture.

PMID- 22999408
TI  - Cricoid pressure, can it still be done?

PMID- 22999409
TI  - Is there a recommendation for safety in the practice of regional anesthesia?

PMID- 22999410
TI  - Nursing students' experience of using a personal digital assistant (PDA) in
      clinical practice - an intervention study.
AB  - BACKGROUND: A personal digital assistant (PDA) is a multifunctional information
      and communication tool allowing nursing students to keep up to date with
      expanding health related knowledge. OBJECTIVES: This study was aimed at exploring
      nursing students' experience of using a PDA in clinical practice. METHOD: In this
      intervention study, nursing students (n=67) used PDAs during a period of 15
      weeks, replied to questionnaires, and participated in focus group interviews.
      RESULTS: The PDA was found to support nursing students in clinical practice and
      to have the potential to be a useful tool with benefits for both the patients and
      for the students. The PDA was regarded as useful, and was presumed to imply
      increased confidence and time savings, and contribute to improved patient safety
      and quality of care. CONCLUSIONS: With available mobile technology, nursing
      students would be able to access necessary information, independent of time and
      place. Therefore, it is important that stakeholders and educators facilitate the
      use of PDAs to support nursing students during their clinical practice, in order
      to prepare them for their future work, and to continuously improve the safety and
      quality of healthcare.

PMID- 22999411
TI  - Pancreatectomy for adenocarcinoma in elderly patients: postoperative outcomes and
      long term results: a study of the French Surgical Association.
AB  - AIM: To determine the benefit of surgery for resectable pancreatic
      adenocarcinomas (PAs) in elderly patients. METHODS: From 2004 to 2009, 932
      patients with resectable PAs underwent pancreatectomies without neoadjuvant
      treatment in 37 institutions. The patients were divided into three groups
      according to age: <70 years (control group; n = 580); 70-79 years (70s group, n =
      288), and >= 80 years (80s group; n = 64). Preoperative, intraoperative,
      postoperative, and histological data were recorded to assess the postoperative
      course and survival. RESULTS: Preoperative or intraoperative characteristics, and
      the histological findings were comparable in the three groups. Postoperative
      mortality and morbidity rates did not differ in the three groups. Adjuvant
      therapies were more frequently used in younger patients than in elderly patients
      (p < 0.01). The overall 1-year, 3-year, and 5-year survival rates of control
      group/70's group/80's group were 82.2%/75.7%/75.7%, 49.9%/41.8%/31%, and
      38.7%/33.2%/0%, respectively (p = 0.16). The median survival of the control, 70s,
      and 80s groups was 24 months, 35.3 months, and 30 months, respectively. Four
      independent prognostic indicators were identified by multivariate analysis:
      venous invasion (hazard ratio (HR) = 2.12), arterial invasion (HR = 2.96),
      positive lymph nodes (HR = 2.25), and adjuvant treatment (HR = 0.65).
      CONCLUSIONS: Fit elderly patients with resectable PAs should not be excluded from
      surgical resection of PA solely because of their real age. Moreover, elderly
      patients seem to obtain similar advantages from pancreatectomies than younger
      patients.

PMID- 22999412
TI  - Combined evaluation of centromere protein H and Ki-67 as prognostic biomarker for
      patients with gastric carcinoma.
AB  - AIM: Centromere protein H (CENP-H) is one of the essential components of the
      human active kinetochore which close links with carcinogenesis. Its expression
      and clinical value of prognostic prediction for gastric cancer (GC) is unclear.
      METHODS: CENP-H and Ki-67 expressions in specimens from 166 patients with GC were
      determined by tissue microarrays and immunostaining. Their correlations between
      patients' clinicopathologic features and prognosis were explored. For mechanisms,
      quantitative CENP-H examination on gastric cancer tissue and cell lines was
      performed via real-time quantitative PCR and Western Blot. Its effect on Survivin
      expression and cell function was evaluated via CENP-H knocking down (SiRNA) or
      overexpression. RESULTS: Highly expression of CENP-H was found in 85 of 166 GC,
      showing a significant correlation with tumour size, depth of infiltration, lymph
      node metastasis, distant metastasis and UICC staging of gastric carcinoma (P <
      0.05), as well as clinical prognosis (coefficient = 0.550, P < 0.001).
      Multivariate analysis revealed that combined CENP-H and Ki67 expression was a
      more valuable independent prognostic predictor for patients' survival (hazard
      ratio, 2.18; P = 0.0109). Furthermore, total mRNA and protein expression of CENP
      H in GC tissue and cell lines were noticeably increased. Survivin expression and
      cell function including growth, proliferation and clonogenic ability could be
      inhibited by CENP-H siRNA or enhanced by overexpressing CENP-H. CONCLUSION: High
      expression of CENP-H in GC indicates poor prognosis and Survivin may mediate its
      procancer role. Combined evaluation of CENP-H and Ki-67 aids in predicting the
      clinical prognosis.

PMID- 22999413
TI  - Norethisterone acetate alters coagulation gene expression in vitro in human cell
      culture.
AB  - INTRODUCTION: Both oestrogen and progestin and the route of administration have
      been implicated in cardiovascular and thromboembolic risk in post menopausal
      hormone users. Transdermal preparations have been reported as safer indicating
      that liver derived metabolites of oestrogen may be important. The aim of our
      study was to investigate the in vitro effects of 17beta-estradiol, its
      metabolites, and norethisterone acetate (NETA) on the expression of coagulation
      genes in cultured human cells. METHODS: Human hepatocytes and human umbilical
      vein endothelial cells(HUVECS) were treated with 17beta-estradiol, estrone, 2
      hydroxyestradiol (2-OH), NETA and NETA/17beta-estradiol (10nM) for 24hours.
      Fibrinogen, factor VII, prothrombin and plasminogen activator inhibitor -1 (PAI
      1) mRNA expression was determined in hepatocyte cultures using TaqMan PCR. Tissue
      factor (TF), tissue factor pathway inhibitor (TFPI), tissue plasminogen activator
      (tPA) and PAI-1 expression was determined in HUVECS. Expression of estrogen
      receptors was also determined. RESULTS: Fibrinogen and factor VII mRNA expression
      was upregulated 2-4 fold by estradiol and estrone. Addition of NETA downregulated
      fibrinogen and prothrombin. PAI-1 expression in hepatocytes was upregulated by
      estrone, 2-OH, NETA and NETA/17beta-estradiol. In HUVECS, TF, TFPI and PAI-1
      expression was upregulated by estrone but not by 17beta-estradiol. NETA
      upregulated TF, TFPI and tPA expression. Estrogen receptor status was unaffected
      by the addition of NETA. CONCLUSIONS: This data suggests a role for progestins in
      modifying the effects of oestrogen and its metabolites on coagulation gene
      expression which may contribute to the reduced thrombotic risk associated with
      transdermal preparations.

PMID- 22999414
TI  - The effects of warfarin and edoxaban, an oral direct factor Xa inhibitor, on
      gammacarboxylated (Gla-osteocalcin) and undercarboxylated osteocalcin (uc
      osteocalcin) in rats.
AB  - INTRODUCTION: Osteocalcin plays a role in bone homeostasis. The vitamin K cycle
      is essential for the gamma-carboxylation of glutamic acid residues in
      osteocalcin. Some evidence suggests that long-term warfarin therapy, which
      inhibits the vitamin K cycle and prevents gamma-carboxylation, is associated with
      increased bone-fracture risk. The aim of this study was to determine the effects
      of warfarin and edoxaban, a direct factor Xa inhibitor, on the serum
      concentration of total, gamma-carboxylated (Gla-osteocalcin) and
      undercarboxylated osteocalcin (uc-osteocalcin) in rats. MATERIALS AND METHODS:
      Rats received orally administered warfarin or edoxaban, and 24h later serum and
      plasma were prepared. Osteocalcin level in serum was measured with ELISA. A Gla
      osteocalcin was precipitated by the addition of hydroxyapatite, and the resulting
      supernatant was used for measuring uc-osteocalcin. Prothrombin time (PT) of
      plasma was also measured. RESULTS: Warfarin at 1mg/kg (a dose which prolonged PT
      2.62-fold) markedly increased the serum level of uc-osteocalcin and slightly
      increased the total osteocalcin level compared with control in rats. Serum Gla
      osteocalcin significantly decreased by warfarin. Edoxaban at 1mg/kg (an
      antithrombotic dose) and 54mg/kg (a dose which prolonged PT 2.25-fold) had no
      effects on total, uc-, and Gla-osteocalcin levels. CONCLUSIONS: This study
      demonstrates that warfarin impaired the carboxylation of osteocalcin in rats. In
      contrast, edoxaban at or higher doses than needed for an antithrombotic effect
      sustained the circulating Gla-osteocalcin level. These findings suggest that
      edoxaban has no effects on the production of Gla-osteocalcin and thus, may have a
      lower risk of adverse effects on bone health.

PMID- 22999415
TI  - Synthesis of beta-ionone derived chalcones as potent antimicrobial agents.
AB  - A series of chalcones (3a-v) have been synthesized by condensation of beta-ionone
      (1) with a variety of aldehydes (2a-v). The synthesized compounds have been
      screened for their in vitro antimicrobial activity against five bacterial and
      five fungal strains, using disc diffusion assay. The evaluated compounds display
      a wide range of activities, from completely inactive to the highly active
      compounds. Some of the compounds are also active against methicillin resistant
      staphylococcus aureus (MRSA).

PMID- 22999416
TI  - The first activation study of a bacterial carbonic anhydrase (CA). The
      thermostable alpha-CA from Sulfurihydrogenibium yellowstonense YO3AOP1 is highly
      activated by amino acids and amines.
AB  - The alpha-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered
      thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (SspCA) was
      investigated for its activation with a series of amino acids and amines. D-His, L
      Phe, L-Tyr, L- and D-Trp were the most effective SspCA activators, with
      activation constants in the range of 1-12 nM, whereas L-His, L/D-DOPA, D-Tyr, and
      several biogenic amines/catecholamines were slightly less effective activators
      (K(A) in the range of 37 nM-0.97 MUM). The least effective SspCA activator was d
      Phe (K(A) of 5.13 MUM). The thermal stability, robustness and very high catalytic
      activity of SspCA make this enzyme an ideal candidate for biomimetic CO(2)
      capture processes.

PMID- 22999417
TI  - "Drinking buddies" and alcohol dependence symptoms among African American men and
      women in Baltimore, MD.
AB  - BACKGROUND: Social network characteristics have been found to be associated with
      a variety of risky behaviors, including alcohol consumption. This study assessed
      the relationships between the characteristics of drinking buddies and alcohol
      dependence symptoms among a sample of African American men and women. METHODS:
      This is a cross-sectional study using baseline data from 721 impoverished African
      American men and women participating in an HIV prevention study in Baltimore, MD.
      Alcohol dependence symptoms were assessed through the Alcohol Use Disorders
      Identification Test (AUDIT) and was defined as AUDIT score>=13 for females and
      AUDIT score>=15 for males. Logistic regression models with generalized estimating
      equations (GEE) using network member as the unit of analysis were conducted to
      assess the associations between the gender or relationship (i.e., kin, non-kin or
      sex partner) of the drinking buddies and the participants' alcohol dependence
      symptoms. RESULTS: Approximately 22% of the participants had alcohol dependence
      symptoms. Among male participants, alcohol dependence symptoms were associated
      with having drinking buddies who were sex partners (AOR: 2.41; 95%CI: 1.32, 4.39)
      or who were female (AOR: 2.29; 95%CI: 1.29, 4.05). Among female participants,
      association between the presence of drinking buddy and alcohol dependence
      symptoms did not depend on the types of relationship or the gender of the
      drinking buddy. CONCLUSIONS: Social network characteristics with respect to
      alcohol dependence symptoms vary according to the type of relationship or the
      gender of the drinking buddies, especially among men. Gender-specific norm-based
      interventions may be a useful strategy to decrease drink problems.

PMID- 22999418
TI  - Smoke-free policies in drinking venues predict transitions in alcohol use
      disorders in a longitudinal U.S. sample.
AB  - BACKGROUND: Smoke-free legislation prohibiting smoking in indoor public venues,
      including bars and restaurants, is an effective means of reducing tobacco use and
      tobacco-related disease. Given the high comorbidity between heavy drinking and
      smoking, it is possible that the public health benefits of smoke-free policies
      extend to drinking behaviors. However, no prior study has examined whether
      tobacco legislation impacts the likelihood of alcohol use disorders (AUDs) over
      time. The current study addresses this gap in the literature using a large,
      prospective U.S. sample. METHOD: Using data from the National Epidemiological
      Survey on Alcohol and Related Conditions (NESARC), we utilized logistic
      regression to examine whether the implementation of state-wide smoke-free
      legislation in bars and restaurants between Waves I (2001-2002) and II (2004
      2005) predicted changes in DSM-IV AUD status (remission, onset, recurrence) in
      current drinkers at Wave I (n=19,763) and participants who drank in public >=once
      per month (n=5913). RESULTS: Individuals in states that implemented smoke-free
      legislation in drinking venues had a higher likelihood of AUD remission compared
      to participants in states without such legislation. Among public drinkers, smoke
      free legislation was associated with a greater likelihood of AUD remission and a
      lower likelihood of AUD onset. These findings were especially pronounced among
      smokers, men, and younger age groups. DISCUSSION: These results demonstrated the
      protective effects of smoke-free bar and restaurant policies on the likelihood of
      AUDs; furthermore, these findings call attention to an innovative legislative
      approach to decrease the morbidity and mortality associated with AUDs.

PMID- 22999419
TI  - Development and process evaluation of a Web-based responsible beverage service
      training program.
AB  - BACKGROUND: Responsible beverage service (RBS) training designed to improve the
      appropriate service of alcohol in commercial establishments is typically
      delivered in workshops. Recently, Web-based RBS training programs have emerged.
      This report describes the formative development and subsequent design of an
      innovative Web-delivered RBS program, and evaluation of the impact of the program
      on servers' knowledge, attitudes, and self-efficacy. METHODS: Formative
      procedures using focus groups and usability testing were used to develop a Web
      based RBS training program. Professional alcohol servers (N = 112) who worked as
      servers and/or mangers in alcohol service settings were recruited to participate.
      A pre-post assessment design was used to assess changes associated with using the
      program. RESULTS: Participants who used the program showed significant
      improvements in their RBS knowledge, attitudes, and self-efficacy. CONCLUSIONS:
      Although the current study did not directly observe and determine impact of the
      intervention on server behaviors, it demonstrated that the development process
      incorporating input from a multidisciplinary team in conjunction with feedback
      from end-users resulted in creation of a Web-based RBS program that was well
      received by servers and that changed relevant knowledge, attitudes, and self
      efficacy. The results also help to establish a needed evidence base in support of
      the use of online RBS training, which has been afforded little research
      attention.

PMID- 22999420
TI  - Understanding the toxicity of carbon nanotubes.
AB  - Because of their unique physical, chemical, electrical, and mechanical
      properties, carbon nanotubes (CNTs) have attracted a great deal of research
      interest and have many potential applications. As large-scale production and
      application of CNTs increases, the general population is more likely to be
      exposed to CNTs either directly or indirectly, which has prompted considerable
      attention about human health and safety issues related to CNTs. Although
      considerable experimental data related to CNT toxicity at the molecular,
      cellular, and whole animal levels have been published, the results are often
      conflicting. Therefore, a systematic understanding of CNT toxicity is needed but
      has not yet been developed. In this Account, we highlight recent investigations
      into the basis of CNT toxicity carried out by our team and by other laboratories.
      We focus on several important factors that explain the disparities in the
      experimental results of nanotoxicity, such as impurities, amorphous carbon,
      surface charge, shape, length, agglomeration, and layer numbers. The exposure
      routes, including inhalation, intravenous injection, or dermal or oral exposure,
      can also influence the in vivo behavior and fate of CNTs. The underlying
      mechanisms of CNT toxicity include oxidative stress, inflammatory responses,
      malignant transformation, DNA damage and mutation (errors in chromosome number as
      well as disruption of the mitotic spindle), the formation of granulomas, and
      interstitial fibrosis. These findings provide useful insights for de novo design
      and safe application of carbon nanotubes and their risk assessment to human
      health. To obtain reproducible and accurate results, researchers must establish
      standards and reliable detection methods, use standard CNT samples as a reference
      control, and study the impact of various factors systematically. In addition,
      researchers need to examine multiple types of CNTs, different cell lines and
      animal species, multidimensional evaluation methods, and exposure conditions. To
      make results comparable among different institutions and countries, researchers
      need to standardize choices in toxicity testing such as that of cell line, animal
      species, and exposure conditions. The knowledge presented here should lead to a
      better understanding of the key factors that can influence CNT toxicity so that
      their unwanted toxicity might be avoided.

PMID- 22999421
TI  - Analysis of basic compounds by supercritical fluid chromatography: attempts to
      improve peak shape and maintain mass spectrometry compatibility.
AB  - While neutral and acidic compounds are well separated by supercritical fluid
      chromatography (SFC), basic analytes are more challenging to separate and often
      problems occur with their peak shapes. Two different methods were explored in the
      present paper to reduce these problems and maintain compatibility with mass
      spectrometry (MS). Five different, commercially available 2-ethylpyridine (2-EP)
      stationary phases were tested without a mobile phase additive using 92
      pharmaceutical compounds with basic properties. The kinetic performances of the 5
      columns were nearly identical, but the peak shapes of the basic drugs were
      strongly affected by the stationary phase. The PrincetonSFC 2-EP and Zymor
      Pegasus 2-EP phases clearly outperformed the other stationary phases, with 77%
      and 69% of the compounds having Gaussian peaks (and asymmetries between 0.8 and
      1.4), respectively. Comparatively, the Waters Viridis Silica 2-EP, Waters Viridis
      BEH 2-EP and ES industries GreenSep 2-EP phases provided only 52%, 44% and 22% of
      the compounds with Gaussian peaks, respectively. These differences were
      attributed to the significant dissimilarities in their silica matrix properties.
      An alternative strategy was also performed with a hybrid silica stationary phase,
      Viridis BEH, using 20mM ammonium hydroxide in the mobile phase, which was a
      mixture of CO(2) and MeOH. With these conditions, 81% of the peaks observed for
      the basic analytes were Gaussian; however, this value dropped to 17% and 10% in
      the absence of additive and in the presence of 20mM formic acid, respectively.
      Finally, the use of a hybrid bare silica stationary phase in the presence of 20mM
      ammonium hydroxide is quite an interesting solution as this system is compatible
      with both ultra high performance SFC (UHPSFC) columns packed with sub-2 MUm
      particles and with MS detection. The overall applicability of this system was
      demonstrated with various mixtures of basic drugs.

PMID- 22999422
TI  - Determination of selected pharmaceutical residues in wastewater using an
      automated open bed solid phase microextraction system.
AB  - The detection of trace levels of pharmaceuticals in environmental matrices
      requires an analyte pre-concentration procedure to obtain the required
      sensitivity for quantitative determination. This research aims to develop a
      simple automated analytical method based on C(18) thin film solid phase
      microextraction (TF-SPME) for the simultaneous extraction of pharmaceutical
      compounds detected in surface waters. As a sample preparation method, solid phase
      microextraction, is a rapid, environmentally friendly, and a sensitive analytical
      technique which isolates and pre-concentrates trace organic pollutants from
      environmental water samples in a single step. High throughput analysis was
      achieved with the use of a robotic auto sampler which enabled parallel analyte
      extraction in a 96-well plate format. Application of the method was demonstrated
      using wastewater from pilot-scale municipal treatment plants and environmental
      water samples from wastewater-dominated reaches of the Grand River (adjacent
      Waterloo, ON) which were analysed using a liquid chromatography-mass spectrometry
      (LC-ESI-MS/MS) technique. The proposed method successfully determined
      concentrations of carbamazepine, fluoxetine, sertraline, and paroxetine in
      treated effluent at concentrations ranging from 240 to 3820 ng/L with a method
      detection limit of 2-13 ng/L with a relative standard deviation of less than 16%.
      Matrix effect was not observed with this method; therefore internal standards are
      not necessary for quantification of target compounds. The results suggest that
      this method is capable of detecting and quantifying many compounds present in
      both wastewater and wastewater-influenced surface water from multiple municipal
      sources. In this study, automated TF-SPME system is demonstrated as a simple and
      fast alternative method for high throughput analysis of pharmaceutical
      contaminants in environmental matrices.

PMID- 22999428
TI  - Reduction in child mortality in Niger: a Countdown to 2015 country case study.
AB  - BACKGROUND: The Millennium Development Goal 4 (MDG 4) is to reduce by two-thirds
      the mortality rate of children younger than 5 years, between 1990 and 2015. The
      2012 Countdown profile shows that Niger has achieved far greater reductions in
      child mortality and gains in coverage for interventions in child survival than
      neighbouring countries in west Africa. Countdown therefore invited Niger to do an
      in-depth analysis of their child survival programme between 1998 and 2009.
      METHODS: We developed new estimates of child and neonatal mortality for 1998-2009
      using a 2010 household survey. We recalculated coverage indicators using eight
      nationally-representative surveys for that period, and documented maternal,
      newborn, and child health programmes and policies since 1995. We used the Lives
      Saved Tool (LiST) to estimate the child lives saved in 2009. FINDINGS: The
      mortality rate in children younger than 5 years declined significantly from 226
      deaths per 1000 livebirths (95% CI 207-246) in 1998 to 128 deaths (117-140) in
      2009, an annual rate of decline of 5.1%. Stunting prevalence decreased slightly
      in children aged 24-35 months, and wasting declined by about 50% with the largest
      decreases in children younger than 2 years. Coverage increased greatly for most
      child survival interventions in this period. Results from LiST show that about
      59,000 lives were saved in children younger than 5 years in 2009, attributable to
      the introduction of insecticide-treated bednets (25%); improvements in
      nutritional status (19%); vitamin A supplementation (9%); treatment of diarrhoea
      with oral rehydration salts and zinc, and careseeking for fever, malaria, or
      childhood pneumonia (22%); and vaccinations (11%). INTERPRETATION: Government
      policies supporting universal access, provision of free health care for pregnant
      women and children, and decentralised nutrition programmes permitted Niger to
      decrease child mortality at a pace that exceeds that needed to meet the MDG 4.
      FUNDING: Bill & Melinda Gates Foundation; World Bank; Governments of Australia,
      Canada, Norway, Sweden, and the UK; and UNICEF.

PMID- 22999429
TI  - A tipping point for child survival, health, and nutrition.

PMID- 22999430
TI  - Strategies to improve health coverage and narrow the equity gap in child
      survival, health, and nutrition.
AB  - Implementation of innovative strategies to improve coverage of evidence-based
      interventions, especially in the most marginalised populations, is a key focus of
      policy makers and planners aiming to improve child survival, health, and
      nutrition. We present a three-step approach to improvement of the effective
      coverage of essential interventions. First, we identify four different
      intervention delivery channels--ie, clinical or curative, outreach, community
      based preventive or promotional, and legislative or mass media. Second, we
      classify which interventions' deliveries can be improved or changed within their
      channel or by switching to another channel. Finally, we do a meta-review of both
      published and unpublished reviews to examine the evidence for a range of
      strategies designed to overcome supply and demand bottlenecks to effective
      coverage of interventions that improve child survival, health, and nutrition.
      Although knowledge gaps exist, several strategies show promise for improving
      coverage of effective interventions-and, in some cases, health outcomes in
      children-including expanded roles for lay health workers, task shifting,
      reduction of financial barriers, increases in human-resource availability and
      geographical access, and use of the private sector. Policy makers and planners
      should be informed of this evidence as they choose strategies in which to invest
      their scarce resources.

PMID- 22999431
TI  - Niger's success in child survival.

PMID- 22999432
TI  - The Countdown for 2015: what lies ahead?

PMID- 22999433
TI  - How changes in coverage affect equity in maternal and child health interventions
      in 35 Countdown to 2015 countries: an analysis of national surveys.
AB  - BACKGROUND: Achievement of global health goals will require assessment of
      progress not only nationally but also for population subgroups. We aimed to
      assess how the magnitude of socioeconomic inequalities in health changes in
      relation to different rates of national progress in coverage of interventions for
      the health of mothers and children. METHODS: We assessed coverage in low-income
      and middle-income countries for which two Demographic Health Surveys or Multiple
      Indicator Cluster Surveys were available. We calculated changes in overall
      coverage of skilled birth attendants, measles vaccination, and a composite
      coverage index, and examined coverage of a newly introduced intervention, use of
      insecticide-treated bednets by children. We stratified coverage data according to
      asset-based wealth quintiles, and calculated relative and absolute indices of
      inequality. We adjusted correlation analyses for time between surveys and
      baseline coverage levels. FINDINGS: We included 35 countries with surveys done an
      average of 9.1 years apart. Pro-rich inequalities were very prevalent. We noted
      increased coverage of skilled birth attendants, measles vaccination, and the
      composite index in most countries from the first to the second survey, while
      inequalities were reduced. Rapid changes in overall coverage were associated with
      improved equity. These findings were not due to a capping effect associated with
      limited scope for improvement in rich households. For use of insecticide-treated
      bednets, coverage was high for the richest households, but countries making rapid
      progress did almost as well in reaching the poorest groups. National increases in
      coverage were primarily driven by how rapidly coverage increased in the poorest
      quintiles. INTERPRETATION: Equity should be accounted for when planning the
      scaling up of interventions and assessing national progress. FUNDING: Bill &
      Melinda Gates Foundation; World Bank; Governments of Australia, Brazil, Canada,
      Norway, Sweden, and UK.

PMID- 22999434
TI  - The comparative cost-effectiveness of an equity-focused approach to child
      survival, health, and nutrition: a modelling approach.
AB  - Progress on child mortality and undernutrition has seen widening inequities and a
      concentration of child deaths and undernutrition in the most deprived
      communities, threatening the achievement of the Millennium Development Goals.
      Conversely, a series of recent process and technological innovations have
      provided effective and efficient options to reach the most deprived populations.
      These trends raise the possibility that the perceived trade-off between equity
      and efficiency no longer applies for child health--that prioritising services for
      the poorest and most marginalised is now more effective and cost effective than
      mainstream approaches. We tested this hypothesis with a mathematical-modelling
      approach by comparing the cost-effectiveness in terms of child deaths and
      stunting events averted between two approaches (from 2011-15 in 14 countries and
      one province): an equity-focused approach that prioritises the most deprived
      communities, and a mainstream approach that is representative of current
      strategies. We combined some existing models, notably the Marginal Budgeting for
      Bottlenecks Toolkit and the Lives Saved Tool, to do our analysis. We showed that,
      with the same level of investment, disproportionately higher effects are possible
      by prioritising the poorest and most marginalised populations, for averting both
      child mortality and stunting. Our results suggest that an equity-focused approach
      could result in sharper decreases in child mortality and stunting and higher cost
      effectiveness than mainstream approaches, while reducing inequities in effective
      intervention coverage, health outcomes, and out-of-pocket spending between the
      most and least deprived groups and geographic areas within countries. Our
      findings should be interpreted with caution due to uncertainties around some of
      the model parameters and baseline data. Further research is needed to address
      some of these gaps in the evidence base. Strategies for improving child nutrition
      and survival, however, should account for an increasing prioritisation of the
      most deprived communities and the increased use of community-based interventions.

PMID- 22999435
TI  - The interaction of subjective experience and attitudes towards specific
      antipsychotic-related adverse effects in schizophrenia patients.
AB  - BACKGROUND: Discontinuation of antipsychotic drugs in schizophrenia patients is a
      major concern, since it results in relapse and re-hospitalizations. Non-adherence
      is strongly associated with negative-subjective response to antipsychotics, which
      is composed of the subjective experience of negative drug effects and attitude
      towards the treatment. OBJECTIVE: To investigate the elements of subjective
      experience and subjective attitude towards specific drug-related adverse effects,
      leading to a generally negative-subjective attitude towards antipsychotics.
      METHODS: Schizophrenia inpatients (n=84) were administered a questionnaire
      measuring attitude and experience on eight subscales: weight gain, sedation,
      sexual anhedonia, extra-pyramidal syndrome, affective flattening, excessive
      sleep, diminished sociability and metabolic syndrome. DAI-30 was used to measure
      attitude towards drugs, and PANSS to assess psychopathology. RESULTS: Weak
      correlation was found between subjective experience and attitude on most of the
      subscales. The only strong, albeit inverse, correlation between experience and
      attitude that was found was with regard to affective flattening, experienced by
      37% of the sample, and it also predicted negative drug attitude as measured by
      the DAI-30, RR: 1.87 (95% CI: 1.06-3.3, df=1, chi(2)=4.525, P<0.05). CONCLUSION:
      Negative attitude towards most adverse drug effects did not correlate with
      personal experience. Drug-related affective flattening should be evaluated
      routinely, since experiencing it may predict negative attitude towards drugs,
      potentially leading to poor compliance and relapse.

PMID- 22999436
TI  - Gender differences in emotional and behavioral disorders and service use among
      adolescent smokers: a nationwide Israeli study.
AB  - Marked gender differences have been identified in cigarette smoking. In this
      study, we aimed to identify the gender-specific emotional and behavioral
      disorders among adolescent smokers and their consequent utilization of mental
      health services. We performed a nationwide survey study of an Israeli
      representative sample of 906 adolescents and their mothers. Mental disorders were
      assessed using the Development and Well-Being Assessment (DAWBA) Inventory.
      Levels of emotional and behavioral difficulties were evaluated using the
      Strengths and Difficulties Questionnaire (SDQ). Mental health services use and
      smoking habits were also assessed. Among non-smoker adolescents there were
      significant gender differences in almost all SDQ scales: emotional problems, pro
      social, hyperactivity/inattention and conduct problems, whereas in the smoker
      group there was a difference only in the SDQ emotional problems scale (both self-
      and maternal-rated, P<0.001 and P=0.002, respectively). Only marginal difference
      was noted between males and females in help-seeking for emotional or behavioral
      problems. Over 50% of both male and female smokers in the study had untreated
      mental disorders (non-significant gender difference). The well-established gender
      differences in psychiatric symptomatology narrowed markedly in adolescent
      smokers; the typical gender difference in disruptive behaviors was lost in the
      adolescent smoking population. The implications of these findings are
      particularly relevant to developing more effective gender-specific programs to
      prevent youth smoking, to facilitate quitting and prepare primary care
      practitioners to identify mental disorders and behavioral problems in adolescents
      with a smoking history.

PMID- 22999437
TI  - Looking at my body. Similarities and differences between anorexia nervosa
      patients and controls in body image visual processing.
AB  - BACKGROUND: Body image distortion is a core symptom of eating disorders.
      Functional magnetic resonance imaging (fMRI) studies on body image processing,
      described different patterns of neural response, mainly involving the inferior
      and superior parietal lobules, and the dorsolateral prefrontal cortex (DLPFC),
      with conflicting results. METHODS: The neural response to the view of their own
      body pictures (normal size and distorted) was evaluated in 18 female anorexia
      nervosa (AN) restricting type patients, and in 19 healthy female subjects (HC)
      using fMRI. Clinical assessment was performed by means of the structured clinical
      interview for DSM-IV and self-reported questionnaires. RESULTS: In response to
      the body image distortion, patients and controls showed an inverse pattern of
      activation, with the widest extent of activation in the oversize condition in AN,
      while in the undersize condition in HC. AN and HC showed a similar pattern of
      neural response to the view of their own body, with an increased activation in
      the extrastriate body area, superior and inferior parietal lobule and prefrontal
      areas, although the extent of activation in HC was more limited as compared with
      AN patients. Increased activity in AN patients, compared with HC, was observed in
      the DLPFC in response to the oversized body picture and a significant correlation
      was found in AN patients between DLPFC activation and eating disorder
      psychopathology. CONCLUSIONS: Our findings suggest the existence of a continuum
      from normalcy to pathology in neural response to body image, and confirm the
      clinical relevance of body image distortion in AN, reinforcing the key role of
      attentive, executive and self-evaluation networks in AN visual processing of own
      distorted body image.

PMID- 22999438
TI  - Psychiatric disorders in low birthweight young adults. Prevalence and association
      with assessments at 11 years.
AB  - OBJECTIVE: To compare mental health of 136 young adults without neurosensory
      handicaps born with low birthweight (LBW, birthweight less than 2,000 g) with 132
      adults with normal birthweight (NBW). METHOD: A cohort of moderate LBW and NBW
      young adults were assessed with the Mini-International Neuropsychiatric Interview
      (MINI) at 19 years and the Children Assessment Schedule (CAS) at 11 years of age.
      RESULTS: At 19 years of age, 44 out of 136 (32%) LBW young adults were diagnosed
      with a psychiatric disorder compared to 10% NBW (OR: 2.8; 95% CI: 1.1, 4.5,
      P=0.02). Among the LBW young adults, affective-, anxiety-, ADHD- and antisocial
      personality disorders were most common, and nine subjects (20%) had more than one
      diagnosis. Of 97 LBW subjects examined both at 11 and 19 years of age, 54 (56%)
      were mentally healthy though out adolescence. This was half as many as for
      controls (OR: 0.6; 95% CI: 0.3 to 0.9). CONCLUSION: Moderate LBW was associated
      with an increased risk of psychiatric disorders in young adulthood. Only half of
      LBW young adults stayed healthy throughout adolescence.

PMID- 22999439
TI  - The influence of impaired processing speed on cognition in first-episode
      antipsychotic-naive schizophrenic patients.
AB  - BACKGROUND: Impaired cognition is a prominent feature of schizophrenia. To what
      extent the heterogeneous cognitive impairments can be accounted for by
      considering only a single underlying impairment or a small number of core
      impairments remains elusive. This study examined whether cognitive impairments in
      antipsychotic-naive, first-episode schizophrenia patients may be determined by a
      relative slower speed of information processing. METHOD: Forty-eight
      antipsychotic-naive patients with first-episode schizophrenia and 48 matched
      healthy controls were administered a comprehensive battery of neuropsychological
      tests to assess domains of cognitive impairments in schizophrenia. Composite
      scores were calculated, grouping tests into cognitive domains. RESULTS: There
      were significant differences between patients and healthy controls on global
      cognition and all cognitive domains, including verbal intelligence, processing
      speed, sustained attention, working memory, reasoning and problem solving, verbal
      learning and memory, visual learning and memory, and reaction time. All these
      significant differences, except for verbal intelligence and global cognition,
      disappeared when processing speed was included as a covariate. CONCLUSION: At the
      first stage of illness, antipsychotic-naive patients with schizophrenia display
      moderate/severe impairments in all the cognitive domains assessed. The results
      support the contention of a global cognitive dysfunction in schizophrenia that to
      some extent may be determined by impaired processing speed.

PMID- 22999440
TI  - Mating of Helicoverpa armigera (Lepidoptera: Noctuidae) moths and their host
      plant origins as larvae within Australian cotton farming systems.
AB  - Transgenic (Bt) cotton dominates Australian cotton production systems. It is
      grown to control feeding damage by lepidopteran pests such as Helicoverpa
      armigera. The possibility that these moths might become resistant to Bt remains a
      threat. Consequently, refuge crops (with no Bt) must be grown with Bt cotton to
      produce large numbers of Bt-susceptible moths to reduce the risk of resistance
      developing. A key assumption of the refuge strategy, that moths from different
      host plant origins mate at random, remains untested. During the period of the
      study reported here, refuge crops included pigeon pea, conventional cotton (C3
      plants), sorghum or maize (C4 plants). To identify the relative contributions
      made by these (and perhaps other) C3 and C4 plants to populations of H. armigera
      in cotton landscapes, we measured stable carbon isotopes (delta(13)C) within
      individual moths captured in the field. Overall, 53% of the moths were of C4
      origin. In addition, we demonstrated, by comparing the stable isotope signatures
      of mating pairs of moths, that mating is indeed random amongst moths of different
      plant origins (i.e. C3 and C4). Stable nitrogen isotope signatures (delta(15)N)
      were recorded to further discriminate amongst host plant origins (e.g. legumes
      from non-legumes), but such measurements proved generally unsuitable. Since 2010,
      maize and sorghum are no longer used as dedicated refuges in Australia. However,
      these plants remain very common crops in cotton production regions, so their
      roles as 'unstructured' refuges seem likely to be significant.

PMID- 22999441
TI  - Emergency cardiac resynchronisation in a 4kg infant post surgical closure of
      ventricular septal defect.
AB  - Cardiac resynchronisation therapy (CRT) is an established treatment for adult
      patients with cardiac failure due to mechanical and electrical dyssynchrony. Data
      on CRT in infants are scarce. We report the remarkable success of emergent CRT by
      epicardial pacing of the left ventricular apex in a 4kg infant with left
      ventricular failure due to LV dyssynchrony from left bundle branch block.

PMID- 22999442
TI  - Right-to-left atrial shunting associated with aortic root aneurysm: a case report
      of a rare cause of platypnea-orthodeoxia syndrome.
AB  - Platypnea-orthodeoxia is a rare syndrome characterised by dyspnoea and hypoxaemia
      worsened on upright posture. We report the case of a 76 year-old man treated for
      lung adenocarcinoma who had developed severe hypoxaemia due to right-to-left
      shunt through a patent foramen ovale (PFO). Diagnosis was suspected by systemic
      uptake of isotope during lung scintigraphy performed to exclude pulmonary
      embolism. Arterial blood gas analysis in supine and upright positions
      demonstrated orthodeoxia. Contrast-enhanced transoesophageal echocardiography
      revealed a slightly redundant atrial septum and large right-to-left shunt through
      a PFO despite normal pulmonary pressure. Chest computed tomography and
      echocardiography showed a 59-mm aneurysm of the thoracic aorta. The opening of
      the PFO seemed to be the result of mechanical deformation of the atrial septum by
      aortic root dilatation. Transcatheter closure of the atrial defect has provided
      excellent results, including a rapid increase in systemic saturation and
      improvement of symptoms without any complications.

PMID- 22999443
TI  - Aztreonam for inhalation solution, challenges to drug approval and integration
      into CF care.

PMID- 22999444
TI  - Prevention of complications related to the use of prosthetic meshes in prolapse
      surgery: guidelines for clinical practice.
AB  - The objective of the study was to provide guidelines for clinical practice from
      the French College of Obstetrics and Gynecology (CNGOF), based on the best
      evidence available, concerning adverse events related to surgical procedures
      involving the use of prosthetic meshes. French and English-language articles from
      Medline, PubMed, and the Cochrane Database were searched, using key words (mesh;
      pelvic organ prolapse; cystocele; rectocele; uterine prolapse; complications;
      adverse event; sacral colpopexy; extrusion; infection). As with any surgery,
      recommendations include perioperative smoking cessation (Expert opinion) and
      compliance with the prevention of nosocomial infections (regulatory
      recommendation). There is no evidence to recommend routine local or systemic
      estrogen therapy before or after prolapse surgery using mesh, regardless of the
      surgical approach (Grade C). Antibiotic prophylaxis is recommended, regardless of
      the approach (Expert opinion). It is recommended to check for pre-operative
      urinary tract infection and treat it (Expert opinion). The first procedure should
      be undertaken under the guidance of a surgeon experienced in the relevant
      technique (Grade C). It is recommended not to place a non-absorbable synthetic
      mesh into the rectovaginal septum when a rectal injury occurs (Expert opinion).
      Placement of a non-absorbable synthetic mesh into the vesicovaginal septum may be
      considered after suturing of a bladder injury if the suture is considered to be
      satisfactory (Expert opinion). If a synthetic mesh is placed by vaginal route, it
      is recommended to use a macroporous polypropylene monofilament mesh (Grade B). It
      is recommended not to use polyester mesh for vaginal surgery (Grade B). It is
      permissible to perform hysterectomy associated with the placement of a non
      absorbable synthetic mesh placed by the vaginal route but this is not routinely
      recommended (Expert opinion). It is recommended to minimize the extent of the
      colpectomy (Expert opinion). The laparoscopic approach is recommended for sacral
      colpopexy (Expert opinion). It is recommended not to place and suture meshes by
      the vaginal route when a sacral colpopexy is performed (Grade B). It is
      recommended not to use silicone-coated polyester, porcine dermis, fascia lata,
      and polytetrafluoroethylene meshes (Grade B). It is recommended to use polyester
      (without silicone coating) or polypropylene meshes (Grade C). Suture of the
      meshes to the promontory can be performed using thread/needle or tacks (Grade C).
      Peritonization is recommended to cover the meshes (Grade C). If hysterectomy is
      required, it is recommended to perform a subtotal hysterectomy (Expert opinion).
      Implementation of this guideline should decrease the prevalence of complications
      related to surgical procedures involving the use of prosthetic meshes.

PMID- 22999445
TI  - [Antiepileptic prophylaxis for elective neurosurgery].
AB  - In tumoral surgery, the risk factors for perioperative epilepsy can be roughly
      grouped into two categories: those related to the preoperative patient's
      conditions (type and location of the tumors, their impact on the surrounding
      brain...) and those specifically related to surgery (cerebral edema, parenchymal
      hematoma, surgical approach, complete or incomplete resection...). The first
      category is supposed to be responsible for preoperative and late postoperative
      epilepsy, while the second would be more related to the risk of epilepsy in the
      first postoperative week (or may be even in the first 48hours). It is well
      accepted (but not always respected) by the neuro-oncologists that there is no
      indication for preventive antiepileptic drugs (AED) in a patient with a brain
      tumor that has never presented seizure. However, every seizure crisis must be
      treated medically. Neurosurgical procedure (which is also a key factor for
      controlling epilepsy when it occurs. The AED should then be maintained as
      appropriate. In the absence of preoperative treatment, it has never been shown
      that prophylactic AED significantly decreases the incidence of postoperative
      seizures, early or late. Yet, the opposite has not been shown neither, and many
      groups use AED despite the risk of side effects and an uncertain risk-benefit
      ratio. Currently, postoperative epilepsy is much less frequent than it was 20 or
      30years ago, and the risk of AED side effects also decreases with the latest
      generation of molecules (such as levetiracetam). So, AED risks and benefits tend
      to diminish in parallel, but their relationship is still to be assessed. In
      practice, a modern attitude would restrict prophylactic AED use to the higher
      risk patients (preoperative epilepsy, temporal astrocytoma, the extent of edema
      and mass effect...). A drug of last generation should be used, starting one week
      before surgery. The duration of the treatment should be limited to one week
      postoperatively in the absence of seizure.

PMID- 22999446
TI  - Thirty-three-year-old man presents with abdominal mass with empty scrotum.

PMID- 22999447
TI  - Certificate of need regulations and the diffusion of intensity-modulated
      radiotherapy.
AB  - OBJECTIVE: To better understand the associations between the certificate of need
      regulations and intensity-modulated radiotherapy dissemination. METHODS: Using
      Surveillance, Epidemiology, and End Results-Medicare data, we identified men
      (aged >= 66 years) treated with radiotherapy for prostate cancer who had been
      diagnosed from 2001 to 2007. Using data from the American Health Planning
      Association, we sorted the health service areas (HSAs) according to the
      stringency of certificate of need regulations (low vs high) in that market. We
      assessed our outcomes (ie, the probability of intensity-modulated radiotherapy
      adoption and intensity-modulated radiotherapy use in the HSAs) using Cox
      proportional hazards and Poisson regression models, respectively. RESULTS: The
      low- and high-stringency markets were similar in terms of racial composition (80%
      vs 85% white, P = .08), population density (1085 vs 558 people/square mile, P =
      .08), and income (median $38 683 vs $40 309, P = .44). However, the low
      stringency markets had more patients with stage T1 disease (45% vs 36%, P < .01).
      The probability of intensity-modulated radiotherapy adoption across the 2 groups
      of HSAs was similar (P = .65). However, among the adopting HSAs, those with high
      stringency consistently had greater use of intensity-modulated radiotherapy (P <
      .01). CONCLUSION: The certificate of need regulations fail to create significant
      barriers to entry for intensity-modulated radiotherapy. Among the HSAs that
      acquired intensity-modulated radiotherapy, high-stringency markets demonstrated a
      greater propensity for using intensity-modulated radiotherapy. These findings
      raise questions regarding the ability of the certificate of need regulations to
      control technology dissemination.

PMID- 22999449
TI  - Adult Xp11 translocation associated renal cell carcinoma: time to recognize.

PMID- 22999448
TI  - Successful repair of post-transplant mycotic aneurysm of iliac artery with renal
      graft preservation: a case report.
AB  - OBJECTIVE: To describe the successful repair of a post-transplant iliac artery
      aneurysm with renal graft preservation. METHODS: An aneurysm was detected in an
      asymptomatic 47-year-old male recipient on routine Doppler ultrasonography that
      involved the right external iliac artery and the distal portion of the renal
      artery. Aneurysm resection was performed immediately after diagnosis 3 months
      after transplantation. A polytetrafluorethylene tube graft was used for
      reconstruction of the right external iliac artery. Reconstruction of the renal
      artery required interposition of a vena saphena graft between the proximal
      portion of the renal artery and the polytetrafluorethylene tube. RESULTS: The
      total warm ischemia time used for aneurysm repair and renal transplant
      revascularization was 90 minutes. The postoperative Doppler ultrasound scan
      showed homogeneous graft perfusion. Pathologic and microbiologic examination of
      the resected aneurysm revealed Candida albicans arteritis. The center in which
      the contralateral donor kidney was transplanted had previously reported Candida
      albicans contamination of the preservation solution. The recipient of the
      contralateral kidney lost his graft owing to bleeding complications. Information
      on this incident was acquired by our center only after aneurysm repair.
      Postoperatively, our recipient was given systemic antifungal therapy. At 6
      months, the serum creatinine level was 1.7 mg/dL. CONCLUSION: Although a high
      risk procedure, repair of a mycotic aneurysm with renal graft preservation is
      feasible. Routine microbiologic screening of the preservation solution might help
      to detect and treat donor-transmitted infections in renal transplant recipients.

PMID- 22999450
TI  - Laparoscopic treatment of intrinsic endometriosis of the urinary tract and
      proposal of a treatment scheme for ureteral endometriosis.
AB  - OBJECTIVE: To discuss the contemporary management of urinary tract endometriosis
      and report our experience concerning laparoscopic treatment of intrinsic urinary
      tract endometriosis. METHODS: We performed a retrospective, multicenter study of
      data collected from March 2006 to March 2011. Ten women were referred from
      gynecology, seven with ureteral involvement and hydronephrosis and three with
      bladder involvement, for urologic management. Of the 7 women with hydronephrosis,
      5 were symptomatic, with recurrent urinary tract infections or pain. All 3 women
      with bladder endometriosis had hematuria. All patients had previously undergone
      unsuccessful hormonal therapy. Ureteral endometriosis was extensively
      investigated and treated by laparoscopic excision of endometriotic plaques and
      excision of intrinsic endometriosis of the ureter. Bladder endometriosis was
      treated by partial cystectomy. Some patients also had endometriosis in other
      organs and underwent, for example, wedge resection of sigmoid colon and
      oophorectomy. RESULTS: The median age of the patients was 30 years (range 25-44).
      Seven patients with intrinsic endometriosis of the ureter all had hydronephrosis
      and proximal hydroureter and underwent laparoscopic ureteral segment excision and
      either end-to-end, spatulated uretroureterostomy or ureteral reimplatation with
      psoas hitch. Three patients had hematuria, and cystoscopic biopsy of the bladder
      lesions confirmed intrinsic endometriosis. They were treated with laparoscopic
      partial cystectomy. One patient with bowel symptoms also underwent laparoscopic
      wedge resection of the sigmoid colon and another underwent oophorectomy for a
      chocolate cyst. Most patients also had peritoneal endometriotic plaques excised.
      We did not perform simple ureterolysis. No complications were encountered. The
      median follow-up was 26.5 months (range 4-53), with no return of symptoms or
      recurrence. The annual follow-up examinations included urinalysis and
      ultrasonography of the urinary tract. CONCLUSION: Intrinsic endometriosis can be
      successfully managed with minimally invasive techniques to provide relief of
      symptoms, protect renal function, and prevent recurrence. We describe a
      classification of ureteral endometriosis determined from staging investigations.

PMID- 22999451
TI  - Surgical implantation of artificial urinary device and penile prosthesis through
      trans-scrotal incision for postprostatectomy urinary incontinence and erectile
      dysfunction: synchronous or delayed procedure?
AB  - OBJECTIVE: To compare simultaneous and 2-stage surgical implantation of an
      artificial urinary sphincter (AUS) and penile prosthesis (PP) for patients with
      severe urinary incontinence and erectile dysfunction after prostatectomy.
      METHODS: The data from 23 patients were reviewed, 15 (group 1) underwent
      simultaneous implantation and 8 (group 2) underwent 2-stage surgery. The
      operative time, complications, postoperative pain, incidence of pre- and
      postoperative urinary incontinence, erectile dysfunction rating (International
      Consultation on Incontinence questionnaire, Incontinence Quality of Life,
      International Index of Erectile Function, and Erectile Dysfunction Inventory of
      Treatment Satisfaction), and patient satisfaction were evaluated. RESULTS: The
      mean operative time was 140 minutes for the simultaneous procedure (group 1) and
      105 minutes for AUS placement and 65 minutes for PP placement (group 2). No major
      postoperative complications were recorded. The average postoperative hospital
      stay was 2.5 days after the double-implant procedure and 2.4 days after AUS and
      1.2 days after PP placement. The visual analog scale score at 6 and 24 hours
      after surgery was 5 and 3 in group 1, and 4 and 3 after AUS and 3 and 2 after PP
      (group 2; P > .05). At 1 year, all patients were socially continent, with an
      average International Consultation on Incontinence score of 2 in group 1 and 2 in
      group 2. Of the patients in groups 1 and 2, 65% and 68% were completely dry,
      respectively (P > .05). The Incontinence Quality of Life score increased from 37
      to 84 in group 1 and from 41 to 82 in group 2. The Patient Global Impression of
      Improvement revealed that 92% of group 1 and 95% of group 2 experienced "great
      improvement" (P > .05). The International Index of Erectile Function and Erectile
      Dysfunction Inventory of Treatment Satisfaction score was 70 of 75 and 87 of 100
      in group 1 and 72 of 75 and 86 of 100 in group 2, respectively (P > .05). Group 1
      patients were completely satisfied, and all group 2 patients stated they would
      have preferred synchronous surgery. CONCLUSION: AUS and PP synchronous placement
      is feasible and safe and as effective as the 2-stage procedure, with better
      acceptance by patients.

PMID- 22999452
TI  - Mid-ureteral rupture: a rare complication of urethral catheterization.
AB  - To our knowledge, there are only a few published cases of ureteral injuries
      secondary to urethral catheterization. We present a case of a ureteral rupture
      that occurred by placement of a standard 16-Fr urethral catheter. The ureteral
      injury was identified by computed tomography of the abdomen and pelvis and
      managed with ureteroureteral anastamosis.

PMID- 22999453
TI  - A case of genitourinary Crohn's disease.
AB  - Scrotal swelling in young boys is a common problem. The differential diagnosis
      includes testicular torsion, epididymoorchitis, and idiopathic scrotal edema. We
      report the unusual case of a 17-year-old boy who presented with recurrent
      episodes of penile and scrotal edema as extraintestinal manifestations of Crohn's
      disease. Genitourinary complications of Crohn's disease are not uncommon;
      however, they more typically present in the form of nephrolithiasis, obstructive
      uropathy, and enterovesical fistulization. Few reports have described Crohn's
      disease presenting with isolated genital edema in the absence of associated
      intestinal or systemic symptoms.

PMID- 22999454
TI  - Comment on: Drolet BC, Christopher DA, Fischer SA. Residents' response to duty
      hour regulations--a follow-up national survey. N Engl J Med 2012;366:1657-1659.

PMID- 22999455
TI  - Predictive factors and management of steinstrasse after shock wave lithotripsy in
      pediatric urolithiasis--a multivariate analysis study.
AB  - OBJECTIVE: To define the predictive factors for the formation of steinstrasse
      (SS) after shock wave lithotripsy (SWL) and determine the treatment strategies
      for this complication in pediatric urolithiasis. METHODS: We retrospectively
      reviewed the data of 341 renal units (RUs) treated with SWL for urolithiasis. The
      stone location, stone burden, auxiliary procedures, energy level, and number of
      shock waves were recorded. Statistical analysis was performed to detect the
      predictive factors for the formation of SS. In addition, the treatment of
      children with SS was evaluated. RESULTS: The mean age of the children was 8.31
      years (range 1-17). Episodes of SS developed in 26 RUs (7.6%). Of the 26 RUs, 20
      (77%) were localized in the lower, 5 (19%) in the upper, and 1 (4%) in multiple
      locations in the ureter. The stone burden was the only statistically significant
      factor predicting the formation of SS on logistic regression analysis (P = .001).
      Of the 26 RUs, 17 (65.4%) were successfully managed by repeat SWL monotherapy, 4
      (15.4%) were managed with ureteroscopy after failure of SWL, 1 (3.8%) was managed
      by ureteroscopy monotherapy, and 4 (15.4%) were monitored with conservative
      management with antispasmodic drug plus hydration therapy. The mean number of SWL
      sessions was 1.72. CONCLUSION: The incidence of SS development in children after
      SWL treatment was similar to that in adult series. Our results suggest that the
      stone burden is a significant predictive factor for the development of SS after
      SWL in pediatric urolithiasis. Most children with SS could be easily and safely
      treated by repeat SWL.

PMID- 22999456
TI  - Long-term results of two prospective bladder-sparing trimodality approaches for
      invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio
      chemotherapy.
AB  - OBJECTIVE: To report long-term outcomes of selective organ preservation for
      muscle-invasive bladder cancer (MIBC) using 2 bladder-sparing trimodality
      approaches. MATERIALS AND METHODS: From 1990 to 2010, 80 patients with T2-T4
      bladder cancer were prospectively enrolled in 2 successive bladder-sparing
      protocols. Forty-one patients were treated with neoadjuvant methotrexate,
      cisplatin, and vinblastine (MCV) chemotherapy followed by radiotherapy (60 Gy) in
      complete responders (protocol 1 [P1]) and 39 patients were treated with weekly
      cisplatin concurrent with radiotherapy (64.8 Gy) (protocol 2 [P2]). RESULTS: The
      median follow-up was 72 months (range, 9-204 months). Five and 10-year cumulative
      overall survival for all series were 73% and 60% and the corresponding numbers
      for cancer-specific survival were 82% and 80%, respectively. Of all surviving
      patients, 83% maintained their own bladder. Although there were no significant
      differences in overall survival (P = .820), cancer-specific survival (P = .688)
      and distant metastasis (P = .417) between protocols, complete response rates (P =
      .003), and disease-free survival (P = .031) were significantly higher in P2
      treatment. CONCLUSION: Trimodality therapy with bladder preservation represents a
      real alternative to radical cystectomy (RC) in selected patients. Overall
      survival and cancer-specific survival rates are encouraging with more than 80% of
      survivors retaining functional bladders.

PMID- 22999457
TI  - Stewart R. Reuter, MD, JD: teacher, author, academic leader, friend.

PMID- 22999458
TI  - Analysis of disk volume before and after CT-guided intradiscal and periganglionic
      ozone-oxygen injection for the treatment of lumbar disk herniation.
AB  - PURPOSE: To quantify the change in volume in herniated lumbar disk after computed
      tomography (CT)-guided intradiscal and periganglionic ozone-oxygen injection and
      to assess the effects of patient age, sex, and initial disk volume on disk volume
      changes. MATERIALS AND METHODS: A total of 283 patients with lumbar radiculopathy
      received a single intradiscal (3 mL) and periganglionic (7 mL) injection of an
      ozone-oxygen mixture (ratio, 3:97; ozone concentration, 30 MUg/mL). Under CT
      guidance, intradiscal and periganglionic injection was performed through an
      extraspinal lateral approach with a 22-gauge spinal needle. All disk volume
      changes were evaluated on CT 6 months after the procedure in all patients.
      RESULTS: Initial mean disk volume was 17.37 cm(3) +/- 4.70 (standard deviation;
      range, 8.12-29.15 cm(3)). Disk volume reduction (mean, 7.70% +/- 5.45; range,
      0.29%-22.31%) was seen in 96.1% of treated disks (n = 272) at 6 months after
      treatment and was found to be statistically significant (P < .0001). In 3.9% of
      patients (n = 11), disk volume increased (mean, 0.59% +/- 0.24; range, 0.11%
      0.81%). Patient age correlated negatively with disk volume reduction (r = -0.505;
      P < .0001) at 6 months after treatment, whereas initial disk volume correlated
      positively with volume reduction (r = 0.225; P = .00014) after therapy. No
      correlation was noted between patient sex and disk volume reduction after
      treatment (P = .09). CONCLUSIONS: Intradiscal administration of medical ozone is
      associated with a statistically significant volume reduction of the herniated
      lumbar disk. The volume-reduction effect of ozone correlates negatively with the
      patient's age and positively with initial disk volume.

PMID- 22999459
TI  - Gene copy number variations in breast cancer of Sub-Saharan African women.
AB  - The goal of this study was CGH array profiling of breast cancer from Malian women
      in order to define differences with those from USA. CGH array was performed in 28
      samples, 17 with a triple negative phenotype. The profiles were compared to those
      of 106 tumors from USA. 6 chromosomal regions (6p21, 9q34, 11q13, 12q24, 17q25
      and 22q12.1-22q13.1) were identified with a significant higher rate of copy
      number alterations. These regions contain several genes of interest including
      BCR. FISH and IHC confirmed that BCR was amplified and overexpressed particularly
      in triple negative tumors. Finally, 5 regions presented a high level of
      amplification in two or more samples, including 2 regions located between 9p22.3
      9p23 and 9p23-9p24.1. This study confirms that breast cancers from African women
      present biological differences with those from USA. Larger studies are needed to
      go further in the identification of therapeutic targets that would be specific to
      African women.

PMID- 22999461
TI  - Synthesis and physical properties of new layered double hydroxides based on ionic
      liquids: application to a polylactide matrix.
AB  - Ionic liquids based on tetraalkylphosphonium salts combined with different anions
      (decanoate and dodecylsulfonate) have been used as intercalating agents of
      layered double hydroxides (LDHs) by ion exchange. The synthesized phosphonium
      treated LDHs display a dramatically improved thermal degradation and a
      significant increase in the interlayer distance as confirmed by thermogravimetric
      analysis (TGA) and X-ray Diffraction (XRD), respectively. To highlight the effect
      of thermostable ionic liquids, a very low amount of LDHs has been introduced
      within a polylactide (PLA) matrix and PLA/LDHs nanocomposites have been processed
      in melt by twin-screw extrusion. Then, transmission electron microscopy (TEM)
      analysis has been used to investigate the influence of ILs on the different
      morphologies of these nanocomposites. Even though the thermal stability of PLA
      matrix decreased, an excellent stiffness-toughness compromise has been obtained.

PMID- 22999460
TI  - A cross-country comparison of intensive care physicians' beliefs about their
      transfusion behaviour: a qualitative study using the Theoretical Domains
      Framework.
AB  - BACKGROUND: Evidence of variations in red blood cell transfusion practices have
      been reported in a wide range of clinical settings. Parallel studies in Canada
      and the United Kingdom were designed to explore transfusion behaviour in
      intensive care physicians. The aim of this paper is three-fold: first, to explore
      beliefs that influence Canadian intensive care physicians' transfusion behaviour;
      second, to systematically select relevant theories and models using the
      Theoretical Domains Framework (TDF) to inform a future predictive study; and
      third, to compare its results with the UK study. METHODS: Ten intensive care unit
      (ICU) physicians throughout Canada were interviewed. Physicians' responses were
      coded into theoretical domains, and specific beliefs were generated for each
      response. Theoretical domains relevant to behaviour change were identified, and
      specific constructs from the relevant domains were used to select psychological
      theories. The results from Canada and the United Kingdom were compared. RESULTS:
      Seven theoretical domains populated by 31 specific beliefs were identified as
      relevant to the target behaviour. The domains Beliefs about capabilities
      (confident to not transfuse if patients' clinical condition is stable), Beliefs
      about consequences (positive beliefs of reducing infection and saving resources
      and negative beliefs about risking patients' clinical outcome and potentially
      more work), Social influences (transfusion decision is influenced by team members
      and patients' relatives), and Behavioural regulation (wide range of approaches to
      encourage restrictive transfusion) that were identified in the UK study were also
      relevant in the Canadian context. Three additional domains, Knowledge (it
      requires more evidence to support restrictive transfusion), Social/professional
      role and identity (conflicting beliefs about not adhering to guidelines,
      referring to evidence, believing restrictive transfusion as professional
      standard, and believing that guideline is important for other professionals), and
      Motivation and goals (opposing beliefs about the importance of restrictive
      transfusion and compatibility with other goals), were also identified in this
      study. Similar to the UK study, the Theory of Planned Behaviour, Social Cognitive
      Theory, Operant Learning Theory, Action Planning, and Knowledge-Attitude
      Behaviour model were identified as potentially relevant theories and models for
      further study. Personal project analysis was added to the Canadian study to
      explore the Motivation and goals domain in further detail. CONCLUSIONS: A wide
      range of beliefs was identified by the Canadian ICU physicians as likely to
      influence their transfusion behaviour. We were able to demonstrate similar though
      not identical results in a cross-country comparison. Designing targeted behaviour
      change interventions based on unique beliefs identified by physicians from two
      countries are more likely to encourage restrictive transfusion in ICU physicians
      in respective countries. This needs to be tested in future prospective clinical
      trials.

PMID- 22999462
TI  - Dispersion polymerization of styrene using a polystyrene/poly(L-glutamic acid)
      block copolymer as a stabilizer.
AB  - A block copolymer (PS-b-poly(L-Glu)) composed of polystyrene and poly(l-glutamic
      acid) was used as a stabilizer for dispersion polymerization of styrene. When
      dispersion polymerization of styrene was conducted at 70 degrees C in 80%
      dimethylformamide-water with 0.5 wt% PS-b-poly(L-Glu), spherical polystyrene
      particles with D(n)=0.72 MUm and narrow size distribution were obtained. Whereas
      AIBN concentration did not have any effects on particle size, molecular weight of
      the polystyrene particles was strongly dependent on the initiator concentration.
      As concentration of the PS-b-poly(L-Glu) increased from 0.2 to 1.0 wt%, particle
      size decreased from D(n)=0.91 to 0.69 MUm with keeping surface area occupied by
      one poly(L-glutamic acid) chain about S=50 nm(2). On the other hand, an increase
      in initial concentration of styrene from 2 to 20 wt% caused an increase in
      particle size from D(n)=0.48 to 1.36 MUm and a decrease in surface area per
      poly(L-glutamic acid) block from S=91 to 45 nm(2). Colloidal stability of the
      polystyrene particles in aqueous solution was responsive to pH due to the surface
      grafted poly(L-glutamic acid). For dispersion polymerization of styrene, the PS-b
      poly(L-Glu) functions as both a stabilizer and a surface modifier.

PMID- 22999463
TI  - Characterization of Silver/Bovine Serum Albumin (Ag/BSA) nanoparticles structure:
      morphological, compositional, and interaction studies.
AB  - The primary objective of this study was to elucidate the structure of protein
      conjugated silver nanoparticles prepared by chemical reduction of AgNO(3) and
      bovine serum albumin (BSA) mixture. The role of BSA in the formation of Ag/BSA
      nanoparticles was established by UV-Vis Spectroscopy. The association of silver
      with BSA in Ag/BSA nanoparticles was studied by the decrease in the intensity of
      absorbance peak at 278 nm in UV-Vis spectra and shift in cathodic peak potential
      in cyclic voltammogram. The molar ratio of silver to BSA in the Ag/BSA
      nanoparticles is 27:1, as ascertained by thermogravimetric analysis and atomic
      absorption spectrometry. Based on atomic force microscopy, dynamic light
      scattering and transmission electron microscopy (TEM) measurements, the average
      particle size of nanoparticles was found to be range of 11-15 nm. TEM image
      showed that the nanoparticle has two distinct phases and selected area electron
      diffraction pattern of nanoparticles indicated that the silver phase in Ag/BSA is
      fcc. X-ray photo electron spectroscopy measurements of freshly prepared and argon
      sputtered nanoparticles provided evidence that the outer and inner region of
      nanoparticles are mainly composed of BSA and silver respectively. The structural
      and compositional findings of nanoparticles could have a strong bearing on the
      bioavailability and antimicrobial activity of nanoparticles.

PMID- 22999464
TI  - Engineered-membranes: a novel concept for clustering of native lipid bilayers.
AB  - A strategy for clustering of native lipid membranes is presented. It relies on
      the formation of complexes between hydrophobic chelators embedded within the
      lipid bilayer and metal cations in the aqueous phase, capable of binding two (or
      more) chelators simultaneously Fig. 1. We used this approach with purple
      membranes containing the light driven proton pump protein bacteriorhodopsin (bR)
      and showed that patches of purple membranes cluster into mm sized aggregates and
      that these are stable for months when incubated at 19 degrees C in the dark. The
      strategy may be general since four different hydrophobic chelators (1,10
      phenanthroline, bathophenanthroline, Phen-C10, and 8-hydroxyquinoline) and
      various divalent cations (Ni(2+), Zn(2+), Cd(2+), Mn(2+), and Cu(2+)) induced
      formation of membrane clusters. Moreover, the absolute requirement for a
      hydrophobic chelator and the appropriate metal cations was demonstrated with
      light and atomic force microscopy (AFM); the presence of the metal does not
      appear to affect the functional state of the protein. The potential utility of
      the approach as an alternative to assembled lipid bilayers is suggested.

PMID- 22999465
TI  - Facile preparation of hierarchically porous carbon using diatomite as both
      template and catalyst and methylene blue adsorption of carbon products.
AB  - Hierarchically porous carbons were prepared using a facile preparation method in
      which diatomite was utilized as both template and catalyst. The porous structures
      of the carbon products and their formation mechanisms were investigated. The
      macroporosity and microporosity of the diatomite-templated carbons were derived
      from replication of diatom shell and structure-reconfiguration of the carbon
      film, respectively. The macroporosity of carbons was strongly dependent on the
      original morphology of the diatomite template. The macroporous structure composed
      of carbon plates connected by the pillar- and tube-like macropores resulted from
      the replication of the central and edge pores of the diatom shells with disk
      shaped morphology, respectively. And another macroporous carbon tubes were also
      replicated from canoe-shaped diatom shells. The acidity of diatomite dramatically
      affected the porosity of the carbons, more acid sites of diatomite template
      resulted in higher surface area and pore volume of the carbon products. The
      diatomite-templated carbons exhibited higher adsorption capacity for methylene
      blue than the commercial activated carbon (CAC), although the specific surface
      area was much smaller than that of CAC, due to the hierarchical porosity of
      diatomite-templated carbons. And the carbons were readily reclaimed and
      regenerated.

PMID- 22999466
TI  - Synchronizing nonfouling and antimicrobial properties in a zwitterionic hydrogel.
AB  - In this work, we report a new approach to integrate antimicrobial and nonfouling
      properties into a single platform without compromising each other. To achieve
      this, a zwitterionic hydrogel is conjugated with an antimicrobial agent as a
      leaving group in a way that maintains the zwitterionic form of the hydrogel
      before, during and after drug release, preventing bacteria surface adhesion and
      bulk proliferation simultaneously. The antibacterial salicylate anion contributes
      the negative charge to the initial zwitterionic state and is released through the
      ester linkage hydrolysis. The hydrogel then switches to its final zwitterionic
      state with the carboxylate as its new negatively charged group. We prove that
      this hydrogel can reach one-salicylate-per-monomer drug loading while still
      retaining the nonfouling property at protein and bacteria levels. It was also
      shown that its drug release profile was dictated by the hydrolysis rate of the
      monomer, making it possible to control and tailor the release rate of small
      hydrophilic drugs from the highly hydrated nonfouling polymer matrix.

PMID- 22999467
TI  - The inhibition by interleukin 1 of MSC chondrogenesis and the development of
      biomechanical properties in biomimetic 3D woven PCL scaffolds.
AB  - Tissue-engineered constructs designed to treat large cartilage defects or
      osteoarthritic lesions may be exposed to significant mechanical loading as well
      as an inflammatory environment upon implantation in an injured or diseased joint.
      We hypothesized that a three-dimensionally (3D) woven poly(epsilon-caprolactone)
      (PCL) scaffold seeded with bone marrow-derived mesenchymal stem cells (MSCs)
      would provide biomimetic mechanical properties in early stages of in vitro
      culture as the MSCs assembled a functional, cartilaginous extracellular matrix
      (ECM). We also hypothesized that these properties would be maintained even in the
      presence of the pro-inflammatory cytokine interleukin-1 (IL-1), which is found at
      high levels in injured or diseased joints. MSC-seeded 3D woven scaffolds cultured
      in chondrogenic conditions synthesized a functional ECM rich in collagen and
      proteoglycan content, reaching an aggregate modulus of ~0.75 MPa within 14 days
      of culture. However, the presence of pathophysiologically relevant levels of IL-1
      limited matrix accumulation and inhibited any increase in mechanical properties
      over baseline values. On the other hand, the mechanical properties of constructs
      cultured in chondrogenic conditions for 4 weeks prior to IL-1 exposure were
      protected from deleterious effects of the cytokine. These findings demonstrate
      that IL-1 significantly inhibits the chondrogenic development and maturation of
      MSC-seeded constructs; however, the overall mechanical functionality of the
      engineered tissue can be preserved through the use of a 3D woven scaffold
      designed to recreate the mechanical properties of native articular cartilage.

PMID- 22999469
TI  - [Voiding disorders in childhood: from symptoms to diagnosis].
AB  - The new definitions of voiding disorders in children should be used in clinical
      practice. Two major kinds of voiding disorders are identified: 1) isolated
      primary enuresis as a disorder occurring exclusively during sleep with no daytime
      leakage; 2) urinary dysfunctions that include uninhibited detrusor contraction,
      sphincter hypertonicity, and urethral instability. These dysfunctions may be
      primary or secondary. Constipation as an underlying cause is frequent and usually
      underestimated. The diagnostic process requires one (or more) long consultations.
      After ruling out a urine leak without a voiding disorder and secondary causes
      (constipation, inadequate hydration, poor voiding hygiene, crystalluria, etc.),
      the aim is to distinguish isolated sleep-time disorders (primary enuresis) from
      daytime +/- sleep-time symptoms (primary urinary dysfunctions). Anamnesis, long
      and accurate, can be sensitized by a questionnaire completed at home. The
      physical examination focuses on the exclusion of anatomic abnormalities and local
      inflammation (vulvitis, balanitis, etc.). Diagnostic tests are rarely required at
      the beginning. Urodynamic exploration may be indicated, never at the first
      consultation, in case of primary urinary dysfunction. This diagnostic approach
      provides an appropriate therapeutic decision.

PMID- 22999468
TI  - Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel
      construct for the growth of prostate cancer spheroids.
AB  - Cancer cells cultured in physiologically relevant, three-dimensional (3D)
      matrices can recapture many essential features of native tumor tissues. In this
      study, a hyaluronic acid (HA)-based bilayer hydrogel system that not only
      supports the tumoroid formation from LNCaP prostate cancer (PCa) cells, but also
      simulates their reciprocal interactions with the tumor-associated stroma was
      developed and characterized. HA hydrogels were prepared by mixing solutions of HA
      precursors functionalized with acrylate groups (HA-AC) and reactive thiols (HA
      SH) under physiological conditions. The resultant viscoelastic gels have an
      average elastic modulus of 234 +/- 30 Pa and can be degraded readily by
      hyaluronidase. The orthogonal and cytocompatible nature of the crosslinking
      chemistry permits facile incorporation of cytokine-releasing particles and PCa
      cells. In our bilayer hydrogel construct, the top layer contains heparin (HP)
      decorated, HA-based hydrogel particles (HGPs) capable of releasing heparin
      binding epidermal growth factor-like growth factor (HB-EGF) in a sustained manner
      at a rate of 2.5 wt%/day cumulatively. LNCaP cells embedded in the bottom layer
      receive the growth factor signals from the top, and in response form enlarging
      tumoroids with an average diameter of 85 MUm by day 7. Cells in 3D hydrogels
      assemble into spherical tumoroids, form close cellular contacts through E
      cadherin, and show cortical organization of F-actin, whereas those plated as 2D
      monolayers adopt a spread-out morphology. Compared to cells cultured on 2D, the
      engineered tumoroids significantly increased the expression of two pro-angiogenic
      factors, vascular endothelial growth factor-165 (VEGF(165)) and interleukin-8 (IL
      8), both at mRNA and protein levels. Overall, the HA model system provides a
      useful platform for the study of tumor cell responses to growth factors and for
      screening of anticancer drugs targeting these pathways.

PMID- 22999470
TI  - [Voiding disorders in childhood: from physiology to symptomatology].
AB  - Micturition is a natural event occurring several times a day, the result of a
      complex and partially unknown physiology. It involves different muscles (striated
      and smooth) as well as the central and autonomic nervous systems in an innate
      voiding reflex. This reflex is controlled after 2 years of age. If there is a
      failure or dysfunction of one of these elements, a miction disorder may appear.
      Two types of miction disorders are identified: neuromuscular disorders of the
      bladder and defective central control. Multiple factors such as constipation,
      bladder irritation, or an increase in abdominal pressure can interfere with the
      voiding reflex. The new international definitions and classifications of voiding
      disorders allow an easier clinical approach through careful and complete
      questioning and a simple clinical exam, efficient enough in most cases to provide
      the diagnosis and adapted treatment.

PMID- 22999471
TI  - The unstable 'clone': evidence from monitoring AFLP-based mutations for short
      term clonal genetic variation in two asexual lineages of the grain aphid,
      Sitobion avenae (F.).
AB  - Clones have been in the forefront of biological interest for many years. Even so,
      open discussions continue to surround the concept of clonality, which has been
      recently much debated in the scientific literature, both in terms of
      philosophical meaning as well as empirical determination. Philosophically, the
      clone is the horizontally produced lineage from a single fertlized egg (e.g.
      mammals by division of the fertilized egg and representing a single generation)
      or vertically produced offspring (e.g. aphids representing different successive
      generations) from a single asexual stem mother (originally for a particular
      lineage, following hatching of the overwintering sexual egg in the spring);
      empirically, the aspect of genetic fidelity is also considered important, so
      called clones being assumed to have an identical genome among clone mates. In
      reality of course, such members of a clonal lineage must differ at various
      regions of the genome, since mutation is a fundamental property of the DNA
      itself. Yet few studies have so far set out to show this empirically in
      eukaryotic organisms, which indulge in periods of asexual reproduction,
      sometimes, as in aphids, over many generations. In the present study, we have
      investigated asexual lineages of the grain aphid, Sitobion avenae (F.), a global
      pest of cereals, over five successive generations employing AFLP-PCR molecular
      techniques. Our main interest was to see how much variation was present in the
      early generations and if this variation was transmitted through the asexual
      lineages. By monitoring AFLP-based polymorphisms, we show that, in this aphid
      species, of a total of 110 individuals from two lineages tested (termed SA and
      SB), random mutations (band deletions, more rarely additions) were apparent from
      the third generation onwards, and although some mutations were found to be
      transmitted transgenerationally, others were rarely transmitted through the
      particular lineages they were detected in. Using Arlequin v. 2.0, average gene
      diversity within the lineages was found to be 0.024 +/- 0.013 and 0.031 +/- 0.016
      for SA and SB, respectively. It was also found from the rearing of the lineages
      that one lineage, SA, was more fecund than the other lineage, SB, over the five
      generations (N = 818 vs. N = 358 total stem mothers plus nymphs for the two
      lineages, respectively).

PMID- 22999472
TI  - MicroRNAs miR-21a and miR-93 are down regulated in peripheral blood mononuclear
      cells (PBMCs) from patients with type 1 diabetes.
AB  - INTRODUCTION: It is well established that type 1 diabetes (T1D) is an autoimmune
      disease. Controversial data exists regarding the differential control of the
      immune system in T1D patients compared to unaffected individuals. MicroRNAs
      (miRNAs) are involved in the control of gene expression (by negative regulation
      of gene expression at post-transcriptional level, by mediating translational
      repression or degradation of the mRNA targets). Their potential role in T cell
      activation and autoimmunity is controversial. AIM: We investigated the expression
      profile of miR-21a and miR-93 in PMC samples of 20 T1D patients and 20 healthy
      controls by means of qPCR in different glucose concentrations (basal, 11 nM and
      25 mM), and we analyzed the possible relationship of this expression pattern with
      autoimmunity. RESULTS: MiR-21a was significantly underexpressed in T1D samples
      (media values expression 0.23 +/- 0.05, p < 0.01) compared to controls (values
      less than 1 indicate a decrease in gene expression). When the PMCs were incubated
      with glucose 11 mM and 25 mM, miR-21a expression decreased in controls and
      increased in T1D samples (0.506 +/- 0.05, p < 0.04). MiR-93 was underexpressed in
      T1D patients (0.331 +/- 0.05, p < 0.02) compared to control samples. However,
      when the PBMCs were incubated with glucose, no changes were observed. No
      association with autoimmunity was observed. CONCLUSION: We demonstrated that
      miRNAs have a differential expression in PBMCs from T1D patients compared to
      controls, suggesting that these miRNAs or others could be involved in T cell
      regulation.

PMID- 22999473
TI  - Circulating surfactant protein D is associated to mortality in elderly women: a
      twin study.
AB  - BACKGROUND: Surfactant protein D (SP-D) is produced in the lungs and additional
      mucosal surfaces. Systemic SP-D levels are previously associated to aging-related
      and lifestyle-related disorders and predicts mortality in cardiovascular and
      lung diseases. However, the association between higher serum SP-D levels and
      mortality in the general population is unknown. We hypothesized that increased
      systemic levels of SP-D may be used as prognostic factor for assessing the
      mortality in the elderly. METHODS AND RESULTS: SP-D serum levels were measured in
      689 elderly subjects and mortality ratios were investigated after a 13-year
      follow-up period. Survival analysis showed that increasing quartiles of serum SP
      D levels were associated to mortality in 70+ year old women (hazard ratio [HR],
      1.29; 95% confidence interval [CI], 0.93-1.78; p = 0.032) adjusted for age,
      smoking and BMI. Women with SP-D levels above 2100 ng/ml had significantly
      increased mortality when compared to elderly women with SP-D levels equal to or
      below 2100 ng/ml (HR, 1.45; 95% CI, 1.12-1.88; p = 0.005). The likelihood that
      the female twin with the highest SP-D level died first increased with increasing
      SP-D levels (p = 0.031) - that is, the bigger intra-pair difference in SP-D
      level, the higher the probability that the twin with the highest measure died
      first (odds ratio [OR], 1.66; p = 0.047). CONCLUSION: The study demonstrates that
      higher circulating SP-D levels are associated with increased mortality rate in
      elderly women in this population-based cohort study. SP-D may serve as a
      biomarker to track the cardio-pulmonary health status in elderly women.

PMID- 22999474
TI  - Quantification of limonin in human urine using solid-phase extraction by LC
      MS/MS.
AB  - A highly sensitive liquid chromatography-tandem mass spectrometry method was
      developed and validated for the determination of limonin in human urine using
      podophyllotoxin as internal standard. The analyte and IS were extracted with
      solid-phase extraction and separated by a rapid isocratic elution with 1% formic
      acid/methanol (v:v, 40:60) on an C(18) column (150 mm * 2.1 mm I.D.). The
      detection was performed by mass spectrometry in the multi-reaction-monitoring
      mode. The precursor to product ion transitions of m/z 471.3->161.2 and m/z 397.2
      >313.1 were used to measure the analyte and the IS. The assay was linear over the
      concentration range of 0.0783-10 ng/mL for limonin in human urine. The lower
      limit of quantification was 0.0783 ng/mL and the extraction recovery was larger
      than 76.7% for limonin. The inter- and intra-day precision of the method at three
      concentrations was less than 7.4%. The method was successfully applied to
      pharmacokinetic study of limonin in humans.

PMID- 22999475
TI  - Determination of free and total valproic acid in human plasma by capillary
      electrophoresis with contactless conductivity detection.
AB  - A new approach for the determination of free and total valproic acid in small
      samples of 140 MUL human plasma based on capillary electrophoresis with
      contactless conductivity detection is proposed. A dispersive liquid-liquid
      microextraction technique was employed in order to remove biological matrices
      prior to instrumental analysis. The free valproic acid was determined by
      isolating free valproic acid from protein-bound valproic acid by ultrafiltration
      under centrifugation of 100 MUL sample. The filtrate was acidified to turn
      valproic acid into its protonated neutral form and then extracted. The
      determination of total valproic acid was carried out by acidifying 40 MUL
      untreated plasma to release the protein-bound valproic acid prior to extraction.
      A solution consisting of 10 mM histidine, 10 mM 3-(N-morpholino)propanesulfonic
      acid and 10 MUM hexadecyltrimethylammonium bromide of pH 6.5 was used as
      background electrolyte for the electrophoretic separation. The method showed good
      linearity in the range of 0.4-300 MUg/mL with a correlation coefficient of
      0.9996. The limit of detection was 0.08 MUg/mL, and the reproducibility of the
      peak area was excellent (RSD=0.7-3.5%, n=3, for the concentration range from 1 to
      150 MUg/mL). The results for the free and total valproic acid concentration in
      human plasma were found to be comparable to those obtained with a standard
      immunoassay. The corresponding correlation coefficients were 0.9847 for free and
      0.9521 for total valproic acid.

PMID- 22999476
TI  - Determination of erythrocyte methotrexate polyglutamates by liquid
      chromatography/tandem mass spectrometry after low-dose methotrexate therapy in
      Chinese patients with rheumatoid arthritis.
AB  - Methotrexate (MTX) is currently one of the most widely used drugs for treatment
      of rheumatoid arthritis (RA) through polyglutamation of methotrexate
      polyglutamates (MTXPGs), a process attaching sequential gamma-linked glutamic
      residues to MTX. A new and sensitive LC/MS/MS method was developed and validated
      for determination of whole-blood MTX and total MTX (MTX+MTXPGs), and then
      concentration of MTXPGs was calculated. To determine whole-blood MTX, whole blood
      was precipitated with 50% trifluoroacetic acid, and extraction was performed
      using ethyl acetoacetate. Analytes were subjected to LC/MS/MS analysis using
      positive electrospray ionization. To determine whole-blood total MTX, whole blood
      was incubated with ascorbic acid (200 mM) at 37 degrees C for 3h to enzymatically
      convert the MTXPGs to MTX, and then processed with the same method mentioned
      above. Recoveries of spiked MTX at ppb (ng/mL) level were between 26.2% and 37.8%
      with intra- and inter-day precision less than 15.8% and 11.8%, respectively. The
      lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were 0.5
      ng/mL and 1 ng/mL, respectively. The sensitive LC/MS/MS method was fully
      validated with high selectivity and acceptable accuracy and precision, which was
      successfully applied to determine the erythrocyte methotrexate polyglutamates in
      patients with RA.

PMID- 22999477
TI  - Simultaneous determination of esculin and its metabolite esculetin in rat plasma
      by LC-ESI-MS/MS and its application in pharmacokinetic study.
AB  - A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method operated
      in the negative electrospray ionization (ESI) switching mode has been developed
      and validated for the simultaneous determination of esculin and its metabolite
      esculetin in rat plasma. After addition of internal standards scopoletin, the
      plasma sample was pretreated by solid-phase extraction (SPE), and separated on a
      reversed phase C(18) column with a mobile phase of 0.01% formic acid in water
      (solvent A) and methanol (solvent B) using isocratic elution (A:B=20:80, v/v).
      The detection of target compounds was done in multiple reaction monitoring (MRM)
      mode. The MRM detection was operated in the negative ESI mode using the
      transitions of m/z 339.1 ([M-H](-))->176.7 for esculetin, m/z 176.9 ([M-H](-))
      >133.0 and m/z 191.0 ([M-H](-))->175.9 for scopoletin. The standard curves, which
      ranged from 25 to 3200 ng/mL for esculin with the lowest limit of quantification
      (LLOQ) of 0.25 ng/mL and from 1.25 to 160 ng/mL for esculetin with the LLOQ of
      1.25 ng/mL, were fitted to a 1/x weighted quadratic regression model. The method
      also afforded satisfactory results in terms of the sensitivity, specificity,
      precision (intra- and inter-day, RSD<8.73%), accuracy, recovery as well as the
      stability of the analyte under various conditions. The method was successfully
      applied to study the pharmacokinetics of esculin and its metabolite esculetin in
      rat plasma after oral administration of esculin at a dose of 100mg/kg.

PMID- 22999478
TI  - Simultaneous determination of zopiclone and its degradation product and main
      impurity (2-amino-5-chloropyridine) by micellar liquid chromatography with time
      programmed fluorescence detection: preliminary investigation for biological
      monitoring.
AB  - A simple and reliable HPLC method was developed and validated for the
      simultaneous determination of the hypnotic drug, zopiclone (ZPC) and its
      degradation product and main impurity, 2-amino-5-chloropyridine (ACP). The
      analyses were carried out on BDS Hypersil phenyl column (4.6 mm * 250 mm, 5 MUm
      particle size) using micellar mobile phase consisting of 0.15M SDS, 10% n
      propanol, 0.3% triethylamine, and 0.02 M orthophosphoric acid (pH 3.5) with timed
      programmable fluorescence detection. The proposed method was found to be
      rectilinear over the concentration ranges of 0.5-10.0 MUg/mL for ZPC and 2.5-50
      ng/mL for ACP. Moreover, the method was applied for the determination of ZPC in
      commercial tablets with mean percentage recovery of 99.06+/-1.49. The results of
      the proposed method were statistically compared with those obtained by the
      comparison method revealing no significance differences in the performance of the
      two methods regarding accuracy and precision. Furthermore, the proposed method
      was applied for the detection and determination of ACP in human urine as a marker
      for ZPC intake.

PMID- 22999479
TI  - Placing the Plasmodium falciparum epigenome on the map.
AB  - It is becoming increasingly evident that epigenetic mechanisms that act on and
      regulate chromatin structure play a key role in the development, adaptation, and
      survival of the malaria parasite within its human host. The study of epigenetics
      in Plasmodium falciparum started to flourish in recent years due to improvement
      of genomic technologies. Here we summarize the knowledge gained from genome-wide
      localization profiling of different epigenetic features, and discuss hypotheses
      emerging from the analysis of these 'descriptive' epigenetic maps. Furthermore,
      we highlight key questions to be answered, and provide a glimpse of developments
      required to gain true mechanistic understanding and to lift this maturing field
      to the next level.

PMID- 22999480
TI  - A qualitative study to identify opportunities for improving trauma quality
      improvement.
AB  - BACKGROUND: Quality improvement (QI) is a central tenant of trauma center
      accreditation in most countries, but its effectiveness is largely unknown. We
      sought to explore opportunities for improving trauma QI. METHODS: We performed a
      qualitative research study using grounded theory analyses of interviews with
      medical directors and program managers from 75 verified trauma centers sampled
      from the United States (n = 51), Canada (n = 14), and Australasia (Australia and
      New Zealand [n = 10]) to explore experiences with trauma QI activities and
      identify opportunities for improvement. RESULTS: Most trauma centers indicated
      that they perceived trauma QI to be important and devoted personnel for QI (data
      entry, data analyst, educator, nurse practitioner). Programs identified 5
      principal opportunities to improve trauma QI: (1) ensure resource adequacy (human
      resources, registry maintenance, financial support, institutional support), (2)
      encourage stakeholder participation (engagement, communication, coordination),
      (3) ensure clinical relevance, (4) incorporate evidence-based tools, and (5)
      require provider and QI program accountability. CONCLUSIONS: Quality improvement
      programs exist as accreditation requirements in most centers. However, trauma QI
      practices depend on a range of local and regional factors, and concrete
      opportunities for improvement that address impact and sustainability exist.

PMID- 22999481
TI  - Uncommon ophthalmologic disorders in intensive care unit patients.
AB  - Ophthalmologic complications are frequently encountered in intensive care unit
      (ICU) patients (Grixti et al. Ocul Surf 2012;10(1):26-42). However, eye care is
      often overlooked in the critical care setting or just limited to the ocular
      surface because treatment is focussed on the management of organ failures. Lack
      of awareness about other less common intraocular sight-threatening conditions may
      have a devastating effect on the patient's vision. To identify specific,
      frequently missed uncommon ocular disorders in ICU, a literature review using the
      keywords "Intensive Care," "Eye care," "ITU," "ICU," "Ophthalmological
      disorders," "Eye disorders" was performed. The databases of CINAHL, PuBMed,
      EMBASE, and Cochrane library were searched. The higher quality studies are
      summarized in the table with statements of methodology to clarify the level of
      evidence. The most prevalent ophthalmologic disorders identified in critically
      ill subjects include exposure keratopathy, chemosis, and microbial keratitis. In
      addition, uncommon eye disorders reported in ICU include metastatic endogenous
      endophthalmitis, acute primary angle closure, ischemic optic neuropathy, pupil
      abnormalities, vascular occlusions, and rhino-orbital cerebral mucormycosis.
      Early diagnosis and effective treatment will help to prevent visual loss.

PMID- 22999482
TI  - Shedding light on light in the intensive care unit.

PMID- 22999483
TI  - Multiprofessional survey of protocol use in the intensive care unit.
AB  - PURPOSE: To date, there has been no large multicenter, multiprofessional
      evaluation of protocol and guideline use in the intensive care unit (ICU). The
      primary purpose of this study was to describe national availability, development,
      implementation, and assessment of protocols in ICUs. A secondary objective was to
      compare perceived utility by ease of use, patient safety, cost containment, and
      compliance of protocols between nurses, physicians, and pharmacists. MATERIALS
      AND METHODS: The survey was developed and tested for validity by 15 clinicians
      who identified additional domains of interest. An additional 15 clinicians of the
      3 different professions evaluated the survey for relevancy and appropriateness of
      responses. Three survey experts evaluated survey construction. The survey was
      uploaded to a Web survey tool and pilot tested for clarity and ease of
      completion. RESULTS: The overall response rate for the survey was 18.1% (n =
      614). Popular methods of education for protocol implementation included staff
      meetings (85.3%) and unit-specific in-services (77.7%). Protocols were most often
      updated when new information was available (40.8%) or every 12 months (17.9%).
      The most common limitation to development and implementation was limited
      personnel resources (24.5%) and physicians not wanting to use them (21.3%),
      respectively. Clinicians indicated that protocols made their job easier and
      improved cost containment some or most of the time. Sepsis protocols were
      identified as most useful in promoting patient outcomes by all 3 professions.
      CONCLUSIONS: The types of protocols available appear to be those assisting with
      management of high-alert medications. Overcoming the perceived barriers of
      protocol use within ICUs requires personnel for development and physician
      support. A better protocol review process may be necessary to assure optimal
      content, desired outcomes, and consistency with Institute for Safe Medication
      Practices guidelines.

PMID- 22999485
TI  - Benign fibrous histiocytoma presenting as anal canal polyp: first case report.
AB  - Nonepithelial and nonmelanocytic anal neoplasms are uncommon. The majority are
      mesenchymal tumors, most of which are malignant sarcomas, particularly
      leiomyosarcomas and gastrointestinal stromal tumors. Benign mesenchymal anal
      neoplasms are even rarer. The most common reported cases were anal leiomyomas,
      granular cell tumors, fibroadenomas, and xanthogranulomas. Benign fibrous
      histiocytomas (BFHs) or dermatofibromas are common mesenchymal cutaneous tumors
      that occur in different sites and at any age. Review of the literature did not
      show previous reports of BFH arising in the anal canal region. We report the
      first case of a solitary BFH, an unexpected occurrence of a common tumor type
      presenting as a polyp in an unusual site such as the anus. This rare occurrence
      can present diagnostic challenges for the surgeons and pathologists. Clinically,
      it can be confused with the usual anal tags, fibroepithelial polyps, or
      hemorrhoids. Benign fibrous histiocytoma is a neoplasm with a potential of local
      recurrence and, therefore, carries certain clinical implications for the
      patients' management and follow-up when compared with the common nonneoplastic
      causes of anal polyps such as the anal tags of anal fissures, hemorrhoids, or
      fibroepithelial papilla. Histologically, it should be differentiated from other
      histiocytic lesions. This can be resolved by the application of certain
      histologic features with the appropriate immunohistochemical markers taken within
      the correct clinical context. 

PMID- 22999484
TI  - Attributable costs of patients with candidemia and potential implications of
      polymerase chain reaction-based pathogen detection on antifungal therapy in
      patients with sepsis.
AB  - PURPOSE: The purposes of this study were to calculate attributable costs of
      candidemia in patients with severe sepsis and to obtain preliminary data
      regarding the potential effects of polymerase chain reaction-based pathogen
      detection on antifungal therapy for these patients. METHODS: Patients treated
      between 2004 and 2010 because of severe sepsis were included into this
      retrospective analysis. The hospital management provided annual fixed costs per
      patient-day; data for variable intensive care unit costs were taken from the
      literature. Multiplex polymerase chain reaction (PCR) was used (VYOO, SIRS-Lab,
      Jena, Germany) for pathogen detection in the blood. RESULTS: Thirty-two patients
      with candidemia were identified. Of 874 patients with sepsis, propensity score
      matching found 32 corresponding patients with sepsis but without candida
      infection but similar risk factors for developing candidemia. Attributable costs
      of candidemia were 7713.79 Euro (cost increase, 19.4%). Initiation of antifungal
      therapy was reduced from 67.5 (52.4, 90) hours in the group, where candida
      infection was determined by blood culture, to 31.0 (28.0, 37.5; P < .01) hours
      after detection by multiplex PCR. CONCLUSIONS: Candidemia increases costs of care
      in patients with septic shock. Polymerase chain reaction-based pathogen detection
      significantly reduces the time to initiation of antifungal therapy. This might
      impact on the clinical course of the disease but need to be confirmed in further
      trials.

PMID- 22999486
TI  - Cognitive-behavioral therapy for obsessive-compulsive disorder: a meta-analysis
      of treatment outcome and moderators.
AB  - The present investigation employed meta-analysis to examine the efficacy of
      cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) as
      well as potential moderators that may be associated with outcome. A literature
      search revealed sixteen randomized-controlled trials (RCTs) with a total sample
      size of 756 participants that met inclusion criteria. Results indicated that CBT
      outperformed control conditions on primary outcome measures at post-treatment
      (Hedges's g = 1.39) and at follow-up (Hedges's g = 0.43). Subsequent analyses
      revealed few moderators of CBT efficacy. Neither higher pre-treatment OCD (p =
      0.46) or depression symptom severity (p = 0.68) was significantly associated with
      a decrease in CBT effect size. Similarly, effect size did not vary as a function
      of 'type' of CBT, treatment format, treatment integrity assessment, blind
      assessment, age of onset, duration of symptoms, percentage of females, number of
      sessions, or percent comorbidity. However, active treatments showed smaller
      effect sizes when compared to placebo controls than when compared to waitlist
      controls. Effect sizes were also smaller for adult RCTs than child RCTs.
      Likewise, older age was associated with smaller effect sizes. However, an
      association between age and effect size was not observed when examining child and
      adult samples separately. This review indicates that while CBT is efficacious in
      the treatment of OCD, more research is needed to identify processes that may
      predict more favorable treatment responses.

PMID- 22999487
TI  - BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone
      marrow transplant recipients: treatment response and evidence for nosocomial
      transmission.
AB  - BACKGROUND: BK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a
      significant complication of allogenic hematopoietic stem cell transplantation
      (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC
      typically presents with clinical cystitis, macrohematuria, and increasing urine
      and blood BKV loads. OBJECTIVES: Characterization of children undergoing
      allogeneic HSCT with BK-PyVHC and their clinical and antibody response to
      cidofovir treatment. STUDY DESIGN: By prospective screening of urine and plasma
      in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6
      (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5
      patients and intravesically to 4 patients (3 double treatments). RESULTS:
      Decreasing BKV viremia of>2log(10)copies/mL and clinical resolution was seen in 4
      patients over 5-12 weeks. Responses occurred only in patients mounting BKV
      specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact
      tracing provided evidence of transmission between 2 BKV-seronegative patients,
      but ruled out transmission among the remaining four patients CONCLUSIONS: The
      data suggest that BK-PyVHC may be the result of nosocomial transmission in
      children with low/undetectable BKV antibodies and raises urgent questions about
      appropriate infection control measures and the role of cidofovir.

PMID- 22999488
TI  - Factors associated with symptomatic rhinovirus infection in patients with COPD.
AB  - BACKGROUND: Human rhinoviruses (HRV) can be detected by RT-PCR in a large
      proportion of acute exacerbations of chronic obstructive pulmonary disease
      (AECOPD) but can also be detected in COPD patients without symptoms. OBJECTIVES:
      The purpose of this study was to compare host, virologic and environmental
      factors associated with symptomatic and asymptomatic HRV infection. STUDY DESIGN:
      One hundred twenty-seven patients with COPD were evaluated every 2 months
      routinely and for all respiratory illnesses during a one year period. RT-PCR
      testing for HRV was performed on nasal and sputum samples. Amplification products
      were sequenced to assign species HRV-A, B or C. Clinical, virologic and
      environmental factors were compared for those infected with HRV compared to those
      without HRV infection as well as symptomatic HRV infection and asymptomatic HRV
      infection. RESULTS: HRVs were detected in 29 participants during 20 illnesses and
      11 routine visits. HRV was detected in nasal samples from 15/102 (14.7%)
      illnesses compared to 2/685 (0.4%) routine visits (p<.0001). Sputum samples were
      also more frequently positive from illnesses than routine visits [14/72 (19.4%)
      vs. 16/310 (5.2%) p<.0001]. Contact with school age children was the only factor
      that was significantly associated with HRV infection and symptomatic HRV illness.
      Severity of underlying lung disease and virologic factors were not associated
      with symptomatic illness. CONCLUSIONS: Contact with school aged children is a
      risk factor for both infection and symptomatic HRV illness. Attention to good
      hand hygiene and avoidance of direct contact with ill children may help patients
      with COPD avoid HRV related illness.

PMID- 22999489
TI  - Oestrogen receptor alpha agonist improved long-term ovariectomy-induced spatial
      cognition deficit in young rats.
AB  - Ovariectomy is known as 'surgical menopause' with decreased levels of oestrogen
      in female rodents and its reported risks and adverse effects include cognitive
      impairment. In the brain, oestrogen exerts effects through its receptors,
      oestrogen receptor alpha (ERalpha) and beta (ERbeta). However, the role of
      ERalpha or ERbeta in ovariectomy-induced cognitive impairment needs further
      investigation. Here, we observed that bilaterally ovariectomized 3-month-old rats
      showed obvious spatial learning and memory deficits in the Morris water maze with
      significant loss of neurons and synapses in the hippocampus. In addition to the
      rapid decline in serum oestradiol levels, the expression of ERalpha, but not
      ERbeta, was decreased in the hippocampus starting 1 wk after ovariectomy. Prompt
      4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) treatment (1
      mg/kg.d), an agonist of ERalpha, improved the spatial learning and memory ability
      of ovariectomized rats and rescued ovariectomy-induced neuron loss by up
      regulating the level of BCLxl, an important anti-apoptosis protein. Furthermore,
      PPT treatment also improved ovariectomy-induced hippocampal synapse loss and up
      regulated the levels of synaptic proteins (synapsin I, NR2A and GluR1) and the
      activates of CaMK Pialpha, ERK and Akt. Thus, these results demonstrated that
      ERalpha plays an important role in neuroprotection and that prompt ERalpha rescue
      is effective to improve hippocampal-dependent cognition deficit after long-term
      ovariectomy.

PMID- 22999490
TI  - Application of Regent mechanical valve in patients with small aortic annulus: 3
      year follow-up.
AB  - BACKGROUND: Aortic valve replacement (AVR) with a small aortic annulus is always
      challenging for the cardiac surgeon. In this study, we sought to evaluate the
      midterm performance of implantation with a 17-mm or 19-mm St. Jude Medical Regent
      (SJM Regent) mechanical valve in retrospective consecutive cohort of patients
      with small aortic annulus (diameter <= 19 mm). METHODS: From January 2008 to
      April 2011, 40 patients (31 female, mean age = 47.2 +/- 5.8 years) with small
      aortic annulus (<=19 mm in diameter) underwent aortic valve replacement with a 17
      mm or 19-mm St. Jude Medical Regent (SJM Regent) mechanical valve. Preoperative
      mean body surface area, New York Heart Association class, and mean aortic annulus
      were 1.61 +/- 0.26 m2, 3.2 +/- 0.4, and 18 +/- 1.4 mm respectively. Patients were
      divided into two groups, according to the implantation of 17 mm SJM Regent
      mechanical valve (group 1, n = 18) or 19 mm SJM Regent valve (group 2, n = 22).
      All patients underwent echocardiography examination preoperatively and at one
      year post-operation. RESULTS: There were no early deaths in either group. Follow
      up time averaged 36 +/- 17.6 months. The mean postoperative New York Heart
      Association class was 1.3 +/- 0.6 (p < 0.001). By echocardiography, in group 1,
      the left ventricular ejection fraction (LVEF), left ventricular fraction
      shortening (LVFS), and the indexed effective orifice area (EOAI) increased from
      43.7% +/- 11.6%, 27.3% +/- 7.6%, and 0.70 +/- 0.06 cm2/m2 to 69.8 +/- 9.3%, 41.4
      +/- 8.3%, and 0.92 +/- 0.10 cm2/m2 respectively (P < 0.05), while the left
      ventricular mass index (LVMI), and the aortic transvalvular pressure gradient
      decreased from 116.4 +/- 25.4 g/m2, 46.1 +/- 8.5 mmHg to 86.7 +/- 18.2 g/m2, 13.7
      +/- 5.2 mmHg respectively. In group 2, the LVEF, LVFS and EOAI increased from
      45.9% +/- 9.7%, 30.7% +/- 8.0%, and 0.81 +/- 0.09 cm2/m2 to 77.4% +/- 9.7%, 44.5%
      +/- 9.6%, and 1.27 +/- 0.11 cm2/m2 respectively, while the LVMI, and the aortic
      transvalvular pressure gradient decreased from 118.3 +/- 27.6 g/m2, 44.0 +/- 6.7
      mmHg to 80.1 +/- 19.7 g/m2, 10.8 +/- 4.1 mmHg as well. The prevalence of PPM was
      documented in 2 patients in Group 1. CONCLUSIONS: Patients with small aortic
      annulus and body surface area, experienced satisfactory clinical improvement
      after aortic valve replacement with modern SJM Regent bileaflet prostheses.

PMID- 22999491
TI  - The Cardiac Safety Research Consortium ECG database.
AB  - The Cardiac Safety Research Consortium (CSRC) ECG database was initiated to
      foster research using anonymized, XML-formatted, digitized ECGs with
      corresponding descriptive variables from placebo- and positive-control arms of
      thorough QT studies submitted to the US Food and Drug Administration (FDA) by
      pharmaceutical sponsors. The database can be expanded to other data that are
      submitted directly to CSRC from other sources, and currently includes digitized
      ECGs from patients with genotyped varieties of congenital long-QT syndrome; this
      congenital long-QT database is also linked to ambulatory electrocardiograms
      stored in the Telemetric and Holter ECG Warehouse (THEW). Thorough QT data sets
      are available from CSRC for unblinded development of algorithms for analysis of
      repolarization and for blinded comparative testing of algorithms developed for
      the identification of moxifloxacin, as used as a positive control in thorough QT
      studies. Policies and procedures for access to these data sets are available from
      CSRC, which has developed tools for statistical analysis of blinded new algorithm
      performance. A recently approved CSRC project will create a data set for blinded
      analysis of automated ECG interval measurements, whose initial focus will include
      comparison of four of the major manufacturers of automated electrocardiographs in
      the United States. CSRC welcomes application for use of the ECG database for
      clinical investigation.

PMID- 22999492
TI  - Methodology for patient-specific modeling of atrial fibrosis as a substrate for
      atrial fibrillation.
AB  - Personalized computational cardiac models are emerging as an important tool for
      studying cardiac arrhythmia mechanisms, and have the potential to become powerful
      instruments for guiding clinical anti-arrhythmia therapy. In this article, we
      present the methodology for constructing a patient-specific model of atrial
      fibrosis as a substrate for atrial fibrillation. The model is constructed from
      high-resolution late gadolinium-enhanced magnetic resonance imaging (LGE-MRI)
      images acquired in vivo from a patient suffering from persistent atrial
      fibrillation, accurately capturing both the patient's atrial geometry and the
      distribution of the fibrotic regions in the atria. Atrial fiber orientation is
      estimated using a novel image-based method, and fibrosis is represented in the
      patient-specific fibrotic regions as incorporating collagenous septa, gap
      junction remodeling, and myofibroblast proliferation. A proof-of-concept
      simulation result of reentrant circuits underlying atrial fibrillation in the
      model of the patient's fibrotic atrium is presented to demonstrate the completion
      of methodology development.

PMID- 22999494
TI  - Rationale and design of the multinational observational study assessing insulin
      use: the MOSAIc study.
AB  - BACKGROUND: Although consensus guidelines recommend insulin progression among
      patients with type 2 diabetes (T2DM) who fail to meet glycemic targets over time,
      many fewer patients are progressed than may benefit. We describe the rationale
      and design of the MOSAIc (Multinational Observational Study Assessing Insulin
      use) study, a multinational observational cohort study to identify patient-,
      physician, and health care environment-based factors associated with insulin
      progression for patients with T2DM in real-world practice. METHODS/DESIGN: We
      will enroll 4,500 patients with T2DM taking initial insulin therapy for >=3
      months across 175 physician practice sites in 18 countries. Extensive
      demographic, clinical, and psychosocial data at the patient and physician level
      and practice site characteristics will be collected at baseline and regular
      intervals during a 24-month follow-up period. We will use a multivariable
      logistic regression model to identify predictors of insulin progression and
      highlight potential opportunities for health behavior intervention to improve
      insulin progression rates. Secondary outcomes include evaluating factors
      associated with glycemic control, hypoglycemia, and treatment adherence among
      patients who do and do not progress beyond their initial insulin therapy and
      exploring geographic heterogeneity in treatment. DISCUSSION: Practice site and
      patient recruitment began in 2011 and baseline data will be available in late
      2012. The MOSAIC study's longitudinal observational design as well as the breadth
      and depth of data will be used to explore and quantify predictors of insulin
      progression and to identify potential opportunities for health behavior
      intervention in order to improve T2DM treatment and clinical outcomes.

PMID- 22999493
TI  - Hypertrophic reprogramming of the left ventricle: translation to the ECG.
AB  - Hypertrophic growth of the heart occurs in many clinical scenarios, and it
      confers substantially increased risk of untoward sequelae. Among them, transition
      to ventricular dilation, wall thinning, contractile dysfunction, and a clinical
      syndrome of heart failure are paramount. Left ventricular hypertrophy (LVH) is
      typically diagnosed by either electrocardiography or echocardiography. However,
      these two means of assessing hypertrophic transformation of the left ventricle
      can sometimes disagree. At one level, this may not be surprising as the two
      methodologies are based on entirely divergent signals: electrical potential
      between two places on the surface of the skin and ultrasound energy reflected
      from the ventricle itself. Echocardiography is an effective means of assessing
      ventricular mass, which is a cardinal feature of LVH. Importantly, however, LVH
      is characterized by a wide range of remodeling events beyond simple increases in
      muscle mass. Electrocardiographic changes in LVH are reflective of the
      electrophysiological aspects of hypertrophic transformation. Here, I present an
      overview of the complex biology of left ventricular hypertrophy with an eye
      toward enhancing our understanding of its ECG manifestations.

PMID- 22999495
TI  - Identifying factors inducing trophozoite differentiation into hypnospores in
      Perkinsus species.
AB  - Trophozoites of species of Perkinsus in host tissues readily differentiate into
      hypnospores when incubated in Ray's fluid thioglycollate medium (RFTM). In
      contrast, hypnospores have rarely been observed in vivo, and when reported they
      have been associated with dying hosts. The objective of this study was to
      determine what altered environmental conditions trigger the differentiation of
      Perkinsus trophozoites into hypnospores. In the first part of the study, cultured
      P. chesapeaki trophozoites were exposed to lowered oxygen, acidic pH, increased
      nutrient levels, heat shock, or osmotic shock conditions, and hypnospore density
      was measured. Acidic pH, lowered oxygen, or increased nutrient levels
      significantly increased P. chesapeaki hypnospore formation. In the second part of
      the study, P. olseni and P. marinus trophozoites were exposed to acidic pH,
      lowered oxygen, or increased nutrient levels resulting in hypnospore formation in
      P. olseni but not P. marinus. This study demonstrated that changes in
      environmental conditions consistent with changes expected in decaying tissues or
      with RFTM incubation induce trophozoite differentiation. The response of the
      cultured trophozoites varied between species and between isolates of the same
      species.

PMID- 22999496
TI  - Advanced arterial blood gas analysis in septic shock: a Singaporean nursing case
      review.
AB  - INTRODUCTION: The admission to the intensive care unit with a diagnosis of sepsis
      and/or septic shock is not uncommon. The aim of this article is to present a
      nursing case review of a patient admitted to the intensive care unit with a
      diagnosis of septic shock and the use of bedside acid-base formulae to inform
      clinical decision making. METHOD: We chose to use a case review. This method is
      useful in reporting unusual or rare cases and is typically seen more in medicine
      than in nursing. DISCUSSION: The gentleman in question was a self-presentation
      with a short history of fever and worsening shortness of breath. His condition
      worsened where he required admission to the intensive care unit. The use of
      'advanced' acid-base interpretation to guide his nursing care provided a platform
      from which to advance a deeper understanding of the intricacies the critically
      ill patient often presents. CONCLUSION: The use of case review is enlightening in
      understanding the disease process and the decision-making that accompanies this.
      The lessons learnt are applicable to a wider nursing audience because
      understanding acid-base physiology is beneficial in supporting and advancing
      critical care nursing practice.

PMID- 22999497
TI  - Nursing workload in neurological intensive care units: cross-sectional study.
AB  - BACKGROUND: Nursing workload has been associated with quality of patient care.
      Thus, it is important to measure nursing workload in neurological intensive care
      units (neuro-ICUs). OBJECTIVE: The aims of the study were to assess nursing
      workload in neuro-ICUs and identify independent factors associated with nursing
      workload. METHOD: This descriptive, cross-sectional study was conducted in two
      neuro-ICUs with 11 beds each (for a total of 22 beds) of a private general
      hospital in the city of Sao Paulo, Brazil. Data from the first 24 hours of
      admission to the neuro-ICUs from 100 consecutive patients were collected from the
      hospital database. The Nursing Activities Score (NAS) was used to assess nursing
      workload in the neuro-ICUs. Data were analysed using descriptive and inferential
      statistics and multiple linear regression analysis. Statistical significance was
      set at alpha=0.05. RESULTS: Patients were mostly men (52.00%), had a mean age of
      55.10 years, median length of ICU stay of 2 days, and survival rate of 94.00%.
      Fifty-nine percent of patients were transferred from the surgical ward. Mean NAS
      was 65.18% (standard deviation=6.63%) and the risk of mortality according to the
      Simplified Acute Physiology Score (SAPS II) and the Logistic Organ Dysfunction
      System (LODS) was 17.79% and 16.30%, respectively. CONCLUSION: The present
      results are important for the effective planning and use of nursing resources
      according to the care needs of patients in neuro-ICUs.

PMID- 22999498
TI  - Nurses' perceptions of patient safety climate in intensive care units: a cross
      sectional study.
AB  - OBJECTIVES: To investigate registered nurses' perceptions of the patient safety
      climate in intensive care units and to explore potential predictors for overall
      perception of safety and frequency of incident reporting. RESEARCH
      METHODOLOGY/DESIGN: A cross-sectional design was conducted, using the
      questionnaire Hospital Survey on Patient Safety Culture, measuring 12 patient
      safety climate dimensions: seven at unit and three at hospital level, two
      outcomes and in addition two outcome items. SETTING: Ten intensive care units
      (ICUs) in six hospitals in one hospital trust in Norway. RESULTS: In total, 220
      registered nurses (RNs) responded (72%). Seven of 12 dimensions achieved a RN
      proportion of positive scores over 55%. Five achieved a lower proportion.
      Significant differences in RNs' perceptions of patient safety were found between
      types of units and between the four hospitals. The total variance in the outcome
      measure explained by the model as a whole was for the outcome dimensions "overall
      perception of safety" 32%, and "frequency of incident reporting" 32%. The
      variables at the unit level made a significant contribution to the outcome.
      CONCLUSION: RNs in ICU are most positive to patient safety climate at unit level,
      hence improvements are needed concerning incident reporting, feedback and
      communication about errors and organisational learning and continuous
      improvement.

PMID- 22999499
TI  - The endogenous retroviral envelope protein syncytin-1 inhibits LPS/PHA-stimulated
      cytokine responses in human blood and is sorted into placental exosomes.
AB  - OBJECTIVES: To examine whether syncytin-1 has immune regulatory functions and is
      carried by human placental exosomes. Further, to examine whether corticotropin
      releasing hormone (CRH) can induce the production of syncytin-1. STUDY DESIGN:
      Human placental exosomes were isolated from placental explant, primary
      trophoblast and BeWo cell cultures. The presence of exosomes was confirmed by
      transmission electron microscopy and western blotting. Exosomal protein was
      probed with 3 separate antibodies targeting syncytin-1. Syncytin-1
      immunosuppression was tested, using either a syncytin-1 recombinant ectodomain
      protein or a synthetic peptide with the human syncytin-1 immunosuppressive domain
      sequence, in an in vitro human blood culture system immune challenged with LPS or
      PHA. The inhibition of cytokine production by syncytin-1 was determined by ELISA
      of TNF-alpha, IFN-gamma and CXCL10. BeWo cells were stimulated with CRH or
      vehicle for 24 h. mRNA and Protein was extracted from the cells for real-time PCR
      and western blotting analysis while exosomes were extracted from conditioned
      media for analysis by western blotting. RESULTS: Protein expression of syncytin-1
      was detected in exosomes isolated from placental explants, primary trophoblast
      and BeWo cell cultures. Syncytin-1 recombinant ectodomain was also shown to
      inhibit the production of the Th1 cytokines TNF-alpha and IFN-gamma as well as
      the chemokine, CXCL10 in human blood cells. Finally, this study showed that
      syncytin-1 can be stimulated by CRH. CONCLUSIONS: The presence of syncytin-1 in
      placental exosomes provides a mechanism for syncytin-1 to reach and interact with
      target cells of the maternal immune system and represents a novel mechanism of
      endogenous retroviral mediated immunosuppression that may be relevant for
      maternal immune tolerance.

PMID- 22999501
TI  - Cancer of the cervix uteri.

PMID- 22999502
TI  - Cancer of the corpus uteri.

PMID- 22999503
TI  - Cancer of the ovary, fallopian tube, and peritoneum.

PMID- 22999504
TI  - Trophoblastic disease.

PMID- 22999505
TI  - Pathology of cancers of the female genital tract.

PMID- 22999506
TI  - Principles of chemotherapy.

PMID- 22999507
TI  - Principles of radiation therapy in low-resource and well-developed settings, with
      particular reference to cervical cancer.

PMID- 22999508
TI  - FIGO Cancer Report 2012.

PMID- 22999509
TI  - Cancer of the vulva.

PMID- 22999510
TI  - Cancer of the vagina.

PMID- 22999511
TI  - Blood leukocytes and macrophages of various phenotypes have distinct abilities to
      form podosomes and to migrate in 3D environments.
AB  - Leukocytes migrate through most tissues in the body, a process which takes place
      in 3D environments. We have previously shown that macrophages use the amoeboid
      migration mode in porous matrices such as fibrillar collagen I and the
      mesenchymal mode involving podosomes and matrix proteolysis in dense matrices
      such as Matrigel. Whether such a plasticity may apply to other leukocytes and to
      all subsets of macrophages is unknown. Here, we therefore provide a comparative
      analysis of the in vitro 3D migration modes adopted by primary human leukocytes.
      Blood-derived monocytes, neutrophils and T lymphocytes were found to use the
      amoeboid mode in a porous fibrillar collagen I matrix but were unable to
      infiltrate dense Matrigel and to form podosomes. M2-polarized macrophages and
      elicited peritoneal macrophages formed podosome rosettes, degraded the ECM and
      infiltrated both matrices. In contrast, M1 macrophages were motionless in 2D and
      3D environments, whilst resident macrophages, devoid of podosomes, were only able
      to use the amoeboid mode. Thus, we conclude that whereas all leukocytes use the
      amoeboid mode to migrate through porous matrices, it is only certain macrophages
      that can adopt the mesenchymal mode that permits migration through dense
      matrices. Interestingly, the acquisition of mesenchymal migration capacity by
      macrophages correlates with the presence of podosomes and with their capacity to
      organize those as rosettes, which appears to be modulated by their
      differentiation and polarization states. As a perspective, specific control of
      the mesenchymal migration would be a potential target for therapeutic approaches
      aiming at decreasing macrophage tissue infiltration.

PMID- 22999512
TI  - Sutureless repair for postinfarction cardiac rupture: a simple approach with a
      tissue-adhering patch.

PMID- 22999513
TI  - Early angiographic evaluation after off-pump coronary artery bypass grafting.
AB  - OBJECTIVES: One of the potential drawbacks of off-pump coronary artery bypass is
      reduced patency compared with conventional coronary artery bypass. This study
      examined the systematic angiographic evaluation after off-pump coronary artery
      bypass. METHODS: Of the 1604 consecutive patients who underwent off-pump coronary
      artery bypass over 6 years, 1422 (89%) who underwent postoperative angiography
      were analyzed. Generalized estimating equations logistic analyses were used to
      investigate potential predictors of graft failure (FitzGibbon B or O). RESULTS:
      Bilateral internal thoracic arteries were used in 78% of the patients. The mean
      number of distal anastomoses was 3.7 +/- 1.2. The in-hospital mortality rate was
      0.4%. Recipient coronary diameter less than 1.5 mm (odds ratio [OR], 1.62; 95%
      confidence interval [CI], 1.24-2.11) was an independent predictor of graft
      failure, whereas percent stenosis diameter greater than 75% (OR, 0.71; 95% CI,
      0.53-0.93), sequential graft (OR, 0.69; 95% CI, 0.51-0.94), and left main disease
      (OR, 0.72; 95% CI, 0.53-0.96) were protective factors. In the subanalyses for
      each conduit, percent stenosis diameter was protective against left internal
      thoracic artery failure (OR, 0.61), whereas smaller recipient coronary diameter
      was associated with right gastroepiploic artery and saphenous vein graft failure
      (OR, 2.37 and 2.36, respectively). Left circumflex artery was associated with
      gastroepiploic artery graft failure, whereas sequential graft was again
      protective for the gastroepiploic artery (OR, 4.39 and 0.33, respectively).
      CONCLUSIONS: Smaller coronary diameter would be a predictor of graft failure,
      whereas percent stenosis diameter greater than 75%, sequential graft, and left
      main disease would be protective factors for off-pump bypass grafts.

PMID- 22999514
TI  - Outcomes of axillary artery side graft cannulation for extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: To determine the safety, efficacy, and frequency of side graft
      axillary artery cannulation for extracorporeal membrane oxygenation support and
      compare it with other cannulation techniques. METHODS: From January 2001 to
      October 2011, 308 adult patients were supported with extracorporeal membrane
      oxygenation at a single center. In 81 patients (26.3%), the extracorporeal
      membrane oxygenation circuit was composed of an arterial inflow by a side graft
      sewn to the axillary artery. Of the 308 patients, 166 (53.9%) underwent femoral
      arterial cannulation and 61 (19.8%) underwent ascending aortic cannulation The
      pertinent variables and postprocedural events were retrospectively analyzed in
      this cohort of patients. RESULTS: The most common complication in the axillary
      artery group was hyperperfusion syndrome of the ipsilateral upper extremity (n =
      20, 24.7%), followed by bleeding from the arterial outflow graft (n = 14, 17.3%).
      Lower extremity ischemia and fasciotomy were more frequent after femoral arterial
      cannulation (n = 27, 16%, and n = 18, 10.8%, respectively). The predictors for a
      poor in-hospital outcome for the entire group of patients were age and
      postoperative cerebral vascular accident. The cannulation method was not a
      predictor of in-hospital outcomes. CONCLUSIONS: Extracorporeal membrane
      oxygenation support with side graft axillary artery technique was more frequently
      associated with hyperperfusion syndrome than other cannulation sites. Lower
      extremity ischemia and compartment syndrome was more common after femoral
      arterial cannulation.

PMID- 22999515
TI  - Toxic anterior segment syndrome: Update on the most common causes.
AB  - PURPOSE: To determine how the most common risk factors for toxic anterior segment
      syndrome (TASS) have evolved over the past decade. SETTING: John A. Moran Eye
      Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Cross-sectional
      study. METHODS: This was a retrospective analysis of surveys from centers
      reporting cases of TASS from June 1, 2007, through March 1, 2012, and information
      from visits to afflicted sites between October 1, 2005, and December 31, 2011.
      Results from June 1, 2009, to March 1, 2012, were compared with those collected
      before June 1, 2009. RESULTS: The data from 130 questionnaires and 71 site visits
      were analyzed. The reporting centers performed approximately 69 000 surgeries and
      reported 1454 cases of TASS. Several trends were noted when comparing the most
      recent data with previously reported results. There was a 26% reduction in sites
      reporting inadequate handpiece flushing volumes and a 27% increase in sites using
      a deionized/distilled final rinse. At sites visited, there was a 36% reduction in
      the use of preserved epinephrine and a 36% reduction in the use of enzymatic
      detergents. However, there was a 21% increase in handling of intraocular lenses
      or instrument tips with gloved hands, a 47% increase in poor instrument
      maintenance, and a 34% increase in ultrasound bath use without adequate routine
      cleaning. CONCLUSIONS: Education may have improved some instrument-cleaning and
      perioperative practices that increase the risk for TASS; however, other practices
      may be headed in an unfavorable direction. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 22999516
TI  - Protective effects of ebselen on sodium-selenite-induced experimental cataract in
      rats.
AB  - PURPOSE: To determine whether ebselen has a protective effect or antioxidative
      potential in a sodium-selenite-induced experimental cataract model. SETTING:
      Firat University, Elazig, Turkey. DESIGN: Experimental study. METHODS: Twenty-one
      Sprague-Dawley rat pups were randomly divided into a control group, a sodium
      selenite-induced-cataract group, and an ebselen-treated group; each group
      contained 7 rat pups. Rats in the control group received dimethyl sulfoxide
      (DMSO) intraperitoneally only and rats in the sodium-selenite-induced-cataract
      group received 30 nmol/g body weight sodium selenite subcutaneously and DMSO
      intraperitoneally 10 days postpartum. Rats in the ebselen group received 30
      nmol/g body weight sodium selenite subcutaneously 10 days postpartum and were
      treated with 5 mg/kg body weight ebselen once a day for 4 consecutive days.
      Cataract development was assessed weekly for 3 weeks by slitlamp examination and
      graded using a scale. Reduced glutathione (GSH), total nitrite, and
      malondialdehyde (MDA) levels in lens supernatants were measured at the end of 3
      weeks. RESULTS: In the control group, all lenses were clear. In the ebselen
      treated group, the mean cataract stage was significantly lower than in the sodium
      selenite-induced-cataract group (P = .022). The GSH levels were significantly
      lower in the sodium-selenite-induced-cataract group than in the control and
      ebselen groups (P < .001). The MDA levels were lower in the ebselen group than in
      the sodium-selenite-induced-cataract group (P < .001). The mean total nitrite
      level was significantly lower in the sodium-selenite-induced-cataract group than
      in the ebselen group (P = .001). CONCLUSIONS: Ebselen had a protective effect on
      cataract development in a sodium-selenite-induced experimental model. The
      protective effect of ebselen appears to be due to inhibition of oxidative stress.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 22999517
TI  - Practice development for midwifery education: an innovative way forward.
AB  - Within workplaces there can be several different cultures operating, and it is
      widely recognised that this occurs in health services. Midwifery and maternity
      care has, and continues to face many challenges as services continually change
      and develop to meet the needs of women and their families. To help meet these
      challenges a practice development initiative was undertaken within a large
      maternity service in Australia to improve the learning and workplace culture.
      This service consisted of four separate units providing care for women and their
      families in the antenatal, birthing, postnatal and neonatal periods. The coming
      together of these four units as a service began with the creation of a shared
      values statement which was adopted by all midwifery staff. To obtain evidence of
      the current workplace, observations of practice, the review of women's stories,
      and audits of clinical data were undertaken. Nine midwives were trained and
      supported to facilitate critical discussions of the data. These critical
      discussions, reflections and analysis of the data, led to the identification of
      four domains or key areas the staff prioritised for change. This led to practice
      development groups being formed within the maternity service, who developed
      collaborative and creative ways of thinking about the issues or problems
      identified. This paper highlights how the processes of practice development were
      implemented to improve one of these domains "the learning and workplace culture",
      especially in relation to educational information and resources for women, their
      families and staff. The journey began over three years ago and continues to
      evolve.

PMID- 22999518
TI  - Psychometric properties of the Strengths and Difficulties Questionnaire(3-4) in 3
      year-old preschoolers.
AB  - We provide the first validation data on the Strengths and Difficulties
      Questionnaire (SDQ(3-4)), a brief screening tool for behavioral and emotional
      problems, in preschool children. Parents of a community sample of 1341 Spanish 3
      year-olds and teachers of a sample of 622 children responded to the SDQ(3-4) and
      different measures of psychopathology. Confirmatory factor analysis yielded
      adequate fit of the model to the original structure. Internal consistency (omega
      coefficient) for total scores was .87 for parents and .91 for teachers.
      Convergent validity of SDQ(3-4)-parents' reports with Achenbach's taxonomy and
      diagnostic interview was good, but low for SDQ(3-4)-teachers' reports. The SDQ(3
      4) showed predictive accuracy for discriminating use of mental health services
      and functional impairment. This is the first work presenting empirical evidence
      of the reliability and validity of the parents' and teachers' SDQ(3-4) for
      preschoolers. The SDQ(3-4) presents acceptable psychometric properties for use in
      the identification of preschool children who might have behavioral or emotional
      problems.

PMID- 22999520
TI  - Positive surgical margin at radical prostatectomy: futile or surgeon-dependent
      predictor of prostate cancer death?

PMID- 22999519
TI  - Retrospective comparison of triple-sequence therapies in metastatic renal cell
      carcinoma.
AB  - BACKGROUND: The optimal sequence of targeted therapy in patients with metastatic
      renal cell carcinoma (mRCC) has not been defined. OBJECTIVE: To describe the
      efficacy and toxicity of the most common sequences of targeted therapy, namely,
      receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin
      inhibitor (mTORi), in different sequences after failure of vascular endothelial
      growth factor signaling inhibition (VEGFi) in first-line therapy. DESIGN, SETTING
      AND PARTICIPANTS: Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi
      (n=62) or VEGFi-mTORi-rTKI (n=41) at two German academic centers. INTERVENTION:
      Sequence of systemic targeted treatment. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Response was assessed using Response Evaluation Criteria in Solid
      Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for
      Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS)
      were estimated by the Kaplan-Meier method. Predictors of survival were analyzed
      using Cox regression. RESULTS AND LIMITATIONS: Sequence groups did not
      significantly differ by patient characteristics and response rate following first
      VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence
      interval [CI], 3.8-5.4), 4.1 mo (95% CI, 3.4-4.9) for rTKI treatment, and 5.4 mo
      (95% CI, 2.7-8.1) for mTORi treatment (p=0.400). No differences in PFS were
      observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI).
      Treatment duration following first VEGFi failure (combined second- and third-line
      PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p=0.103).
      No significant differences in OS were observed among sequence groups (33.7 mo
      [95% CI, 30.4-37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4-52.9] for VEGFi
      mTORi-rTKI). Primary resistance on first-line therapy was an independent
      predictor of OS, but type of sequence was not. Limitations are the retrospective
      design and limited numbers of cases. CONCLUSIONS: The sequence therapies VEGFi
      mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be
      equally efficacious in terms of PFS, OS, and response rate, with no apparent
      beneficial effect with an early use of mTORi.

PMID- 22999521
TI  - Establishment of reverse genetics system for infectious bronchitis virus
      attenuated vaccine strain H120.
AB  - Infectious bronchitis virus (IBV) strain H120 was successfully rescued as
      infectious clone by reverse genetics. Thirteen 1.5-2.8 kb fragments contiguously
      spanning the virus genome were amplified and cloned into pMD19-T. Transcription
      grade complete length cDNA was acquired by a modified "No See'm" ligation
      strategy, which employed restriction enzyme Bsa I and BsmB I and ligated more
      than two fragments in one T4 ligase reaction. The full-length genomic cDNA was
      transcribed and its transcript was transfected by electroporation into BHK-21
      together with the transcript of nucleocapsid gene. At 48 h post transfection, the
      medium to culture the transfected BHK-21 cells was harvested and inoculated into
      10-days old SPF embryonated chicken eggs (ECE) to replicate the rescued virus.
      After passage of the virus in ECE five times, the rescued H120 virus (R-H120) was
      successfully recovered. R-H120 was subsequently identified to possess the
      introduced silent mutation site in its genome. Some biological characteristics of
      R-H120 such as growth curve, EID50 and HA titers, were tested and all of them
      were very similar to its parent strain H120. In addition, both R-H120 and H120
      induced a comparable titer of HA inhibition (HI) antibody in immunized chickens
      and also provided up to 85% of immune protection to the chickens that were
      challenged with Mass41 IBV strain. The present study demonstrated that
      construction of infectious clone from IBV vaccine strain H120 is possible and IBV
      H120 can be use as a vaccine vector for the development of novel vaccines through
      molecular recombination and the modified reverse genetics approach.

PMID- 22999522
TI  - Quantitative real-time PCR and culture examination of Mycobacterium avium subsp.
      paratuberculosis at farm level.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease in
      ruminants and may contribute to Crohn's disease in humans. The aim of this study
      was to determine the occurrence and quantity of MAP in cattle feces and milk in
      the Iranian context. In addition, we evaluated the effect of cattle age as well
      as farming system as risk factors contributing to MAP load. For this, a total
      sample of 373 consisting of 150 cattle feces (CF), 150 individual cow's milk
      (ICM), as well as 73 bulk-tank milk (BTM) was collected randomly and regardless
      of the cattle health status. The samples were assayed using F57 quantitative real
      time PCR (qPCR) and culture method. According to the results of qPCR which was
      found ~ 10 times more sensitive than culture assay, MAP was detected in 68.66%
      (103/150) of the CF, 12% (18/150) of the ICM and 52.05% (38/73) of the BTM
      samples. In contrast to the previous reports, the quantity of MAP in the BTM
      (2.03-5.97 log cfu/50 ml) was statistically (p<0.01) higher than the ICM (0.90
      1.97 log cfu/50 ml). Data suggested a direct relation (p<0.01) between the cattle
      age and the quantity of MAP in the CF samples, while the relation was not
      statistically significant (p>0.05) for the ICM. In addition, MAP load in the BTM
      samples obtained from traditional farms was significantly (p<0.01) higher than
      that of the industrial ones, while the differences in CF and ICM was not
      significant (p>0.05).

PMID- 22999523
TI  - Genetic characterization of a novel bovine papillomavirus member of the
      Deltapapillomavirus genus.
AB  - This report describes the complete genomic sequence and taxonomic position of BPV
      type 13. The BPV13 genome was amplified using the multiply primed rolling-circle
      amplification technique and long-template PCR employing two specific primers. The
      two long PCR fragments obtained were cloned and sequenced via primer walking. The
      complete genomic sequence of the BPV13 contains 7961 bp encoding eight proteins,
      E1, E2, E4, E5, E6, E7, L1, and L2. Similarly to the E5 gene in BPVs 1 and 2, the
      putative BPV13 E5 ORF encodes a small transforming protein that contains a
      hydrophobic transmembrane domain. Meanwhile, the retinoblastoma tumor suppressor
      binding domain is absent in the putative BPV13 E7 protein. The presence of these
      two specific molecular features has been recognized as a distinct marker for the
      development of fibropapilloma in artiodactyl PV-induced lesions. The phylogenetic
      analysis demonstrated that BPV13 is a new member of the Deltapapillomavirus
      genus, to be classified as the third representative of the Delta 4 species. The
      characterization of the genomic sequence of this novel PV will aid in the
      interpretation of the pathologies described to be related to this virus and
      provide support for the development of diagnostic tools for epidemiological
      surveillance of BPV13 in its potential natural hosts.

PMID- 22999524
TI  - Dual-source dual-energy computed tomography angiography for active
      gastrointestinal bleeding: a preliminary study.
AB  - AIM: To assess the utility of dual-source dual-energy computed tomography
      angiography (DSDECTA) in the diagnosis of active gastrointestinal bleeding (GIB).
      MATERIALS AND METHODS: From June 2010 to September 2011, 58 consecutive patients
      with clinical signs of active GIB underwent DSDECTA. Two radiologists, blinded to
      clinical data, interpreted images from DSDECTA independently, with discordant
      interpretation resolved by consensus. The standards of reference included digital
      subtraction angiography, endoscopy, surgery, or final pathology reports.
      Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values,
      and accuracy of DSDECTA for detection of active GIB were evaluated. Receiver
      operating characteristic (ROC) analysis was undertaken and the area under the
      curve (AUC) calculated. RESULTS: Active GIB source was identified in 39 of 58
      patients (67.2%), all of which were confirmed by one or more reference standard.
      Negative DSDECTA results were obtained in 19 patients (32.8%). Of these, 15
      patients did not require any further intervention and were discharged without
      incident. The overall sensitivity, specificity, PPV, NPV, and accuracy of DSDECTA
      was 88.6, 100, 100, 73.7, and 91.4%, respectively. The AUC was 0.935 +/- 0.063.
      The dose reduction of a dual-phase DSDECTA protocol was approximately 30%,
      compared with that of a triple-phase protocol used in a previous study.
      CONCLUSION: DSDECTA can act as an accurate method for detection and localization
      of active GIB and has a relatively low radiation dose.

PMID- 22999525
TI  - The genetic and environmental structure of the covariation among the symptoms of
      insomnia, fatigue, and depression in adult females.
AB  - Although the co-occurrence among symptoms of insomnia, fatigue, and depression
      has been frequently reported, the etiology of this co-occurrence remains poorly
      understood. A total of 3,758 adult female twins in the United Kingdom completed a
      mail-out survey including six questions concerning frequency and severity of
      symptoms of insomnia, fatigue, and depression. Correlations among the scores of
      the three symptoms ranged from 0.35 to 0.44. Among various multivariate models we
      tested, the common-pathway model explained the data best. In the best-fitting
      model, the common factor was explained approximately equally by genetic and
      unique environmental factors (49% and 51%, respectively). In addition to the
      common variance, there was a significant specific variance in each symptom, where
      unique environmental factors were much larger than genetic factors. These results
      imply that although there are shared genetic liabilities for the development of
      symptoms of depression, fatigue, and insomnia, it is environmental experiences
      that make etiological distinctions among three symptoms.

PMID- 22999526
TI  - Lack of association between TNF-alpha promoter polymorphisms and multiple
      myeloma: a meta-analysis.
AB  - Results of available literatures, which concerned the association between TNF
      alpha promoter -238/-308 gene polymorphisms and multiple myeloma (MM), are of
      great controversy. A review was performed in studies reporting on the association
      between them. Odds ratios (ORs) with 95% confidence interval (CI) were used to
      evaluate the association. The pooled ORs indicated that there was no association
      between TNF-alpha -238/-308 polymorphisms and MM susceptibility in overall
      population. Sub-group analysis also confirmed that no evidence supported the
      relevance of TNF-alpha promoter -238/-308 gene polymorphisms with MM. Studies
      with large sample size and multi-ethnics may be needed to further explore the
      association between them.

PMID- 22999527
TI  - MPN blast phase: clinical challenge and assessing response.

PMID- 22999528
TI  - Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of
      ruptured human cerebral aneurysms: preliminary results.
AB  - BACKGROUND: M1 and M2 cells are two major subsets of human macrophages that exert
      opposite effects on the inflammatory response. This study aims to investigate the
      role of macrophage M1/M2 imbalance and mast cells in the progression of human
      cerebral aneurysms to rupture. METHODS: Ten patients with cerebral aneurysms
      (five ruptured and five unruptured) underwent microsurgical clipping. During the
      procedure, a segment of the aneurysm dome was resected and immunostained with
      monoclonal antibodies for M1 cells (anti-HLA DR), M2 cells (anti-CD 163), and
      mast cells (anti-tryptase clone AA). A segment of the superficial temporal artery
      (STA) was also removed and immunostained with monoclonal antibodies for M1, M2,
      and mast cells. RESULTS: All ten aneurysm tissues stained positive for M1, M2,
      and mast cells. M1 and M2 cells were present in equal proportions in unruptured
      aneurysms. This contrasted with a marked predominance of M1 over M2 cells in
      ruptured aneurysms (p = 0.045). Mast cells were also prominently upregulated in
      ruptured aneurysms (p = 0.001). Few M1 and M2 cells were present in STA samples.
      CONCLUSIONS: M1/M2 macrophages and mast cells are found in human cerebral
      aneurysms; however, M1 and mast cell expression seems to markedly increase in
      ruptured aneurysms. These findings suggest that macrophage M1/M2 imbalance and
      upregulation of mast cells may have a role in the progression of cerebral
      aneurysms to rupture.

PMID- 22999529
TI  - Time-dependent negative reinforcement of ethanol intake by alleviation of acute
      withdrawal.
AB  - BACKGROUND: Drinking to alleviate the symptoms of acute withdrawal is included in
      diagnostic criteria for alcoholism, but the contribution of acute withdrawal
      relief to high alcohol intake has been difficult to model in animals. METHODS:
      Ethanol dependence was induced by passive intragastric ethanol infusions in
      C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water
      infusions. Mice were then allowed to self-administer ethanol or water
      intragastrically. RESULTS: The time course of acute withdrawal was similar to
      that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to
      9 hours and returning to baseline within 24 hours; withdrawal severity was
      greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial
      ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake
      normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute
      withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake
      persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice
      allowed to drink ethanol during acute withdrawal drank more ethanol and self
      infused more ethanol than nondependent mice (experiment 4). CONCLUSIONS: Alcohol
      access during acute withdrawal increased later alcohol intake in a time-dependent
      manner, an effect that may be related to a genetic difference in sensitivity to
      acute withdrawal. This promising model of negative reinforcement encourages
      additional research on the mechanisms underlying acute withdrawal relief and its
      role in determining risk for alcoholism.

PMID- 22999530
TI  - [Patient and health professional perceptions on the quality of care provided to
      diabetic patients].
AB  - OBJECTIVE: To describe the knowledge and perceptions of patients and health
      professionals on the factors that influence the quality and continuity of care of
      diabetic patients provided in Primary Care. MATERIAL AND METHODS: A qualitative
      study using a phenomenological perspective. PARTICIPANTS: Medical and nursing
      professionals working in Primary Care Centres in the city of Zaragoza, and
      patients with diabetes mellitus attended in the same centres. Two group (focus
      group) and 6 individual interviews were carried out in February and March 2010. A
      predetermined script, with the variables to explore, was used. RESULTS: The
      patients and health professionals interviewed identified problems in assuming
      diabetes as a chronic disease. Among the factors related to success in changing
      habits and lifestyles, were gender (women showed greater difficulties to change),
      type of job and work situation. Health professionals identified the availability
      of guidelines and protocols, and personal motivation as factors that work in
      favour; and lack of time and current information systems as factors that hamper
      the provision of good quality care. There were discrepancies among health
      professionals as regards the role played by patient groups and associations.
      CONCLUSIONS: It is important to take into account the factors that make changes
      in habits and lifestyles difficult, such as gender and the employment situation,
      when designing actions aimed at modifying risk factors in diabetic patients.

PMID- 22999531
TI  - Multimodal imaging and therapy - technology of the future.

PMID- 22999532
TI  - Re: Decreased amplitude of detrusor overactivity by repetitive swallowing: K.
      Stav, E. Lang, D. Leibovici, A. Lindner and J. M. Rabey. J Urol 2012; 187: 1717
      1720.

PMID- 22999533
TI  - Re: Factors affecting kidney function and stone recurrence rate after
      percutaneous nephrolithotomy for staghorn calculi: outcomes of a long-term
      followup: T. Akman, M. Binbay, C. Kezer, E. Yuruk, E. Tekinarslan, F. Ozgor, E.
      Sari, R. Aslan, Y. Berberoglu and A. Y. Muslumanoglu. J Urol 2012; 187: 1656
      1661.

PMID- 22999535
TI  - Novel iron oxide microparticles used to render stone fragments paramagnetic:
      assessment of toxicity in a murine model.
AB  - PURPOSE: We developed novel peptide coated iron oxide supraparamagnetic
      microparticles that bind to calcium stones, allowing for extraction of these
      stones with magnetic tools. Urothelial and fibroblast cell lines show minimal to
      no toxicity when exposed to the particles. Before clinical evaluation, assessment
      of the in vivo systemic toxicity of the microparticles was required. This was
      studied in a murine model. MATERIALS AND METHODS: A total of 64 mice were exposed
      to different concentrations of microparticles (0.5, 1 or 5 mg/dl) intravesically
      or intravenously via the tail vein. Mice were sacrificed at different intervals
      (days 1, 3, 28 and 84). Representative samples from the brain, lung, heart,
      kidney and liver were evaluated histologically at each time point. The tissue
      distribution pattern of the particles and any degree of inflammation was noted by
      a clinical pathologist. Liver function tests were also performed at similar
      intervals. RESULTS: All mice survived until the assigned end point and appeared
      healthy after exposure to microparticles. In the bladder installation group no
      particles were seen in any organ regardless of the particle concentration
      instilled. In the intravenous instillation group there was tissue distribution in
      the liver and to a lesser extent in the lung. There was mild inflammation in the
      liver and lung, which was dose dependent. CONCLUSIONS: Novel iron oxide
      supraparamagnetic microparticles used to render stone fragments paramagnetic in
      the urinary collecting system did not appear to cross intact urothelial
      membranes. When introduced systemically, they led to minimal inflammatory
      changes, predominantly in the liver and lung. Additional long-term studies are
      required.

PMID- 22999534
TI  - Histotripsy focal ablation of implanted prostate tumor in an ACE-1 canine cancer
      model.
AB  - PURPOSE: Histotripsy is a nonthermal ablative focused ultrasound technology with
      possible future applications for prostate cancer focal therapy. We used the ACE-1
      prostate tumor model and evaluated the feasibility of treating prostate tumors
      with histotripsy. MATERIALS AND METHODS: A total of 10 immunosuppressed
      (cyclosporine treated) canine subjects received transrectal ultrasound guided
      percutaneous intraprostatic injection of ACE-1 canine prostate cancer cells.
      Prostates were serially imaged with transrectal ultrasound to monitor tumor
      growth. Subjects were sham treated (3) or underwent transabdominal histotripsy of
      the prostate, which targeted implanted tumor and adjacent parenchyma using a 750
      kHz piezoelectric ultrasound therapy transducer. Prostates were examined
      histologically to confirm tumor and the histotripsy treatment effect. RESULTS:
      ACE-1 tumors were visualized on transrectal ultrasound in all 10 subjects within
      2 weeks of tumor injection. Lesions demonstrated growth in the prostatic capsule,
      glandular lobules, fibrous septa and periurethral stroma with significant
      desmoplastic reaction and areas of central necrosis on histology. Lymph node
      and/or pulmonary metastases developed in 4 subjects. Ultrasound tumor
      localization and initiation of cavitation during histotripsy therapy were
      feasible in all treated subjects. Histologically there was evidence of
      homogenization of tumor and prostatic parenchyma in all 4 acute subjects with
      necrosis and hemorrhage in the 3 chronic subjects. CONCLUSIONS: This study shows
      the feasibility of histotripsy destruction of prostate tumors in a canine ACE-1
      model. It suggests a potential role for histotripsy based focal therapy for
      prostate cancer. Further studies are needed to better characterize the effects of
      histotripsy on malignant tissues.

PMID- 22999536
TI  - Gender identity and gender role orientation in female assigned patients with
      disorders of sex development.
AB  - PURPOSE: Gender identity and gender role orientation were assessed in 24 female
      assigned patients with disorders of sex development. MATERIALS AND METHODS: A
      total of 16 patients were prenatally exposed to androgens, of whom 15 had
      congenital adrenal hyperplasia and 1 was virilized due to maternal tumor. Eight
      patients had 46,XY karyotype, of whom 5 had partial and 3 had complete androgen
      insensitivity syndrome. Gender identity was measured by the 27-item Gender
      Identity/Gender Dysphoria Questionnaire for Adolescents and Adults with 167
      female medical students as controls, and gender role was assessed by the
      femininity and masculinity subscales of the 30-item Bem Sex Role Inventory with
      104 female and 64 male medical students as controls. RESULTS: No patient reached
      the cutoff for gender identity disorder on the Gender Identity/Gender Dysphoria
      Questionnaire for Adolescents and Adults. However, patients with 46,XY karyotype
      demonstrated a somewhat more conflicted gender identity, although the overall
      differences were relatively small. As to gender role orientation, patients with
      complete androgen insensitivity syndrome had high scores on the femininity and
      masculinity scales of the Bem Sex Role Inventory, which made them the most
      androgynous group. CONCLUSIONS: Our findings, although clinically not clear cut,
      suggest that patients with disorders of sex development are a heterogeneous group
      regarding gender identity and gender role outcomes, and that this issue should be
      discussed with the family when treatment plans are made.

PMID- 22999537
TI  - A novel method of evaluating ureteropelvic junction obstruction: dynamic near
      infrared fluorescence imaging compared to standard modalities to assess urinary
      obstruction in a swine model.
AB  - PURPOSE: Dynamic near infrared fluorescence imaging of the urinary tract provides
      a promising way to diagnose ureteropelvic junction obstruction. Initial studies
      demonstrated the ability to visualize urine flow and peristalsis in great detail.
      We analyzed the efficacy of near infrared imaging in evaluating ureteropelvic
      junction obstruction, renal involvement and the anatomical detail provided
      compared to conventional imaging modalities. MATERIALS AND METHODS: Ten swine
      underwent partial or complete unilateral ureteral obstruction. Groups were
      survived for the short or the long term. Imaging was performed with
      mercaptoacetyltriglycine diuretic renogram, magnetic resonance urogram, excretory
      urogram, ultrasound and near infrared imaging. Scoring systems for ureteropelvic
      junction obstruction were developed for magnetic resonance urogram and near
      infrared imaging. Physicians and medical students graded ureteropelvic junction
      obstruction based on magnetic resonance urogram and near infrared imaging
      results. RESULTS: Markers of vascular and urinary dynamics were quantitatively
      consistent among control renal units. The same markers were abnormal in
      obstructed renal units with significantly different times of renal phase peak,
      start of pelvic phase and start of renal uptake. Such parameters were consistent
      with those obtained with mercaptoacetyltriglycine diuretic renography. Near
      infrared imaging provided live imaging of urinary flow, which was helpful in
      identifying the area of obstruction for surgical planning. Physicians and medical
      students categorized the degree of obstruction appropriately for fluorescence
      imaging and magnetic resonance urogram. CONCLUSIONS: Near infrared imaging offers
      a feasible way to obtain live, dynamic images of urine flow and ureteral
      peristalsis. Qualitative and quantitative parameters were comparable to those of
      conventional imaging. Findings support fluorescence imaging as an accurate, easy
      to use method of diagnosing ureteropelvic junction obstruction.

PMID- 22999538
TI  - Differential effects of botulinum neurotoxin A on bladder contractile responses
      to activation of efferent nerves, smooth muscles and afferent nerves in rats.
AB  - PURPOSE: To determine the mechanisms of botulinum neurotoxin A (Metabiologics,
      Madison, Wisconsin) induced inhibition of bladder activity we examined the effect
      of botulinum neurotoxin A on detrusor contractile responses to the activation of
      L-type voltage-gated Ca(2+) channels, and efferent and afferent nerve terminals
      in the rat bladder. MATERIALS AND METHODS: Rat bladder strips were incubated for
      3 hours with different concentrations of botulinum neurotoxin A (0.3 to 100 nM).
      We examined the effect of botulinum neurotoxin A on detrusor contractility in
      response to activation of L-type voltage-gated Ca(2+) channels, and efferent and
      afferent nerve terminals induced by 70 mM KCl, electrical field stimulation and 1
      MUM capsaicin, respectively. RESULTS: Botulinum neurotoxin A inhibited electrical
      field stimulation induced contractions at a concentration of 10 nM or higher. The
      maximal inhibition at 100 nM was 70% compared to that of control strips. KCl
      induced contractions, which were sensitive to nifedipine, were significantly
      inhibited by incubation with botulinum neurotoxin A at a concentration of 3 nM or
      higher. Maximal inhibition at 100 nM was 30% compared to that of control strips.
      Capsaicin induced contractions were not inhibited by 3-hour incubation but they
      were significantly inhibited by overnight incubation with 100 nM botulinum
      neurotoxin A (30% compared to control strips). Carbachol induced contractions
      were not altered by incubation with botulinum neurotoxin A. CONCLUSIONS: The
      order of inhibitory potency of botulinum neurotoxin A was efferent nerve
      terminals >L-type voltage-gated Ca(2+) channels >afferent nerve terminals. Since
      the inhibitory effects on L-type voltage-gated Ca(2+) channels and efferent nerve
      terminals were observed at similar botulinum neurotoxin A concentrations, the
      inhibitory effect of botulinum neurotoxin A on L-type voltage-gated Ca(2+)
      channels may have an important role in regulating and stabilizing bladder
      activity.

PMID- 22999539
TI  - Variations in management of mild prenatal hydronephrosis among maternal-fetal
      medicine obstetricians, and pediatric urologists and radiologists.
AB  - PURPOSE: There are no current guidelines for diagnosing and managing mild
      prenatal hydronephrosis. Variations in physician approach make it difficult to
      analyze outcomes and establish optimal management. We determined the variability
      of diagnostic approach and management regarding prenatal hydronephrosis among
      maternal-fetal medicine obstetricians, pediatric urologists and pediatric
      radiologists. MATERIALS AND METHODS: Online surveys were sent to mailing lists
      for national societies for each specialty. Participants were surveyed regarding
      criteria for diagnosing mild prenatal hydronephrosis and recommendations for
      postnatal management, including use of antibiotic prophylaxis, followup
      scheduling and type of followup imaging. RESULTS: A total of 308 maternal-fetal
      medicine obstetricians, 126 pediatric urologists and 112 pediatric radiologists
      responded. Pediatric urologists and radiologists were divided between Society for
      Fetal Urology criteria and use of anteroposterior pelvic diameter for diagnosis,
      while maternal-fetal medicine obstetricians preferred using the latter. For
      postnatal evaluation radiologists preferred using personal criteria, while
      urologists preferred using anteroposterior pelvic diameter or Society for Fetal
      Urology grading system. There was wide variation in the use of antibiotic
      prophylaxis among pediatric urologists. Regarding the use of voiding
      cystourethrography/radionuclide cystography in patients with prenatal
      hydronephrosis, neither urologists nor radiologists were consistent in their
      recommendations. Finally, there was no agreement on length of followup for mild
      prenatal hydronephrosis. CONCLUSIONS: We observed a lack of uniformity regarding
      grading criteria in diagnosing hydronephrosis prenatally and postnatally among
      maternal-fetal medicine obstetricians, pediatric urologists and pediatric
      radiologists. There was also a lack of agreement on the management of mild
      intermittent prenatal hydronephrosis, resulting in these cases being managed
      inconsistently. A unified set of guidelines for diagnosis, evaluation and
      management of mild intermittent prenatal hydronephrosis would allow more
      effective evaluation of outcomes.

PMID- 22999540
TI  - Re: A double-blind randomized controlled clinical trial to assess the effect of
      Doppler optimized intraoperative fluid management on outcome following radical
      cystectomy: P. Pillai, I. McEleavy, M. Gaughan, C. Snowden, I. Nesbitt, G.
      Durkan, M. Johnson, J. Cosgrove and A. Thorpe. J Urol 2011; 186: 2201-2206.

PMID- 22999544
TI  - Re: Lower testosterone levels with luteinizing hormone-releasing hormone agonist
      therapy than with surgical castration: new insights attained by mass
      spectrometry: T. M. van der Sluis, H. N. Bui, E. J. Meuleman, A. C. Heijboer, J.
      F. Hartman, N. van Adrichem, E. Boeve, W. de Ronde, R. J. van Moorselaar and A.
      N. Vis. J Urol 2012; 187: 1601-1606.

PMID- 22999546
TI  - Stage, grade and behavior of bladder urothelial carcinoma defined by the microRNA
      expression profile.
AB  - PURPOSE: We identified miRNA expression profiles in urothelial carcinoma that are
      associated with grade, stage, and recurrence-free and disease specific survival.
      MATERIALS AND METHODS: The expression of 14 miRNAs was evaluated by quantitative
      reverse transcriptase-polymerase chain reaction in surgical specimens from 30
      patients with low grade, noninvasive (pTa) and 30 with high grade, invasive (pT2
      3) urothelial carcinoma. Controls were normal bladder tissue from 5 patients who
      underwent surgical treatment for benign prostatic hyperplasia. Endogenous
      controls were RNU-43 and RNU-48. miRNA profiles were compared and Kaplan-Meier
      curves were constructed to analyze disease-free and disease specific survival.
      RESULTS: miR-100 was under expressed in 100% of low grade pTa specimens (p
      <0.001) and miR-10a was over expressed in 73.3% (p <0.001). miR-21 and miR-205
      were over expressed in high grade pT2-3 disease (p = 0.02 and <0.001,
      respectively). The other miRNAs were present at levels similar to those of normal
      bladder tissue or under expressed in each tumor group. miR-21 over expression
      (greater than 1.08) was related to shorter disease-free survival in patients with
      low grade pTa urothelial carcinoma. Higher miR-10a levels (greater than 2.30)
      were associated with shorter disease-free and disease specific survival in
      patients with high grade pT2-3 urothelial carcinoma. CONCLUSIONS: Four miRNAs
      were differentially expressed in the 2 urothelial carcinoma groups. miR-100 and
      miR-10a showed under expression and over expression, respectively, in low grade
      pTa tumors. miR-21 and miR-205 were over expressed in pT2-3 disease. In addition,
      miR-10a and miR-21 over expression was associated with shorter disease-free and
      disease specific survival. miRNAs could be incorporated into the urothelial
      carcinoma molecular pathway. These miRNAs could also serve as new diagnostic or
      prognostic markers and new target drugs.

PMID- 22999547
TI  - MYC copy number gains are associated with poor outcome in penile squamous cell
      carcinoma.
AB  - PURPOSE: We determined MYC gene numerical aberrations and protein expression at
      different stages of penile squamous cell carcinoma carcinogenesis. We correlated
      these findings with clinicopathological parameters and HPV infection. MATERIALS
      AND METHODS: We evaluated 79 cases of penile squamous cell carcinoma, including
      11 in situ and 68 invasive carcinomas. The MYC cytogenetic profile was evaluated
      by fluorescence in situ hybridization. HPV was detected by polymerase chain
      reaction amplification. RESULTS: MYC gains were identified in 4 of 11 in situ
      carcinomas (36%) and 50 of 68 invasive penile squamous cell carcinomas (73%). A
      significant association between MYC gains, and tumor progression and poor outcome
      was demonstrated (p <0.05). HPV DNA was detected in 32 of 79 penile squamous cell
      carcinomas (39%). High risk type 16 was the most prevalent type. MYC numerical
      aberrations did not correlate with HPV status. A significant association between
      HPV and MYC protein over expression was noted. In HPV negative cases MYC gains
      correlated with MYC over expression. CONCLUSIONS: MYC gains progressively
      increased during penile squamous cell carcinoma progression from in situ samples
      to metastases. MYC gains were an independent factor for poor prognosis. These
      findings were independent of HPV infection. MYC expression was increased in
      samples with HPV infection, probably reflecting direct activation of MYC.

PMID- 22999548
TI  - The effect of micronized purified flavonoid fraction on the prevention of
      testicular pathologies in adolescent rats with experimentally induced varicocele.
AB  - PURPOSE: We investigated the effect of micronized purified flavonoid fraction on
      the prevention of testicular pathologies following varicocele induction.
      MATERIALS AND METHODS: A total of 66 adolescent (6-week-old) male Wistar rats
      were included in study. Rats were divided into 7 groups, including group 1-
      control, group 2--sham operation, group 3--left varicocele induced, group 4-
      varicocele induced, varicocelectomy done 4 weeks later and micronized purified
      flavonoid fraction administered for 4 weeks, group 5--varicocele induced and
      micronized purified flavonoid fraction administered for 8 weeks, group 6-
      varicocele induced and beginning 4 weeks later micronized purified flavonoid
      fraction administered for 4 weeks, and group 7--varicocele induced and
      varicocelectomy done 4 weeks later. Before sacrifice bilateral real-time
      testicular microvascular perfusion of all rats was measured using the PeriFlux
      System 5000 PF 5010 LDPM Unit (Perimed, Jarfalla, Sweden). All testes were graded
      according to the Johnsen scoring system. To assess apoptosis caspase-3 levels
      were measured. RESULTS: Testicular weight in group 3 was markedly decreased and
      the extent of seminiferous tubular damage was significantly increased compared
      with the other groups. Bilateral testicular blood flow and the number of
      apoptotic germ cells were greater in group 3. Significantly higher Johnsen scores
      and a meaningful decrease in the apoptotic index were detected in groups 4 to 7
      compared with group 3. CONCLUSIONS: We observed favorable effects of micronized
      purified flavonoid fraction on the regression of testicular damage secondary to
      varicocele.

PMID- 22999549
TI  - Controlled regulation of erythropoietin by primary cultured renal cells for renal
      failure induced anemia.
AB  - PURPOSE: Renal failure induced anemia develops as a result of inadequate
      production of erythropoietin, which is the primary regulator of red blood cell
      production. We previously noted that culture expanded primary renal cells stably
      express erythropoietin and suggested that these cells may be used as a potential
      treatment for renal failure induced anemia. We investigated whether these cells
      are able to regulate erythropoietin expression in a controlled manner under
      different oxygen and environmental conditions. MATERIALS AND METHODS: Primary rat
      renal cells were exposed to different hypoxic (0.1% to 1% O(2)) and normoxic
      environments. Erythropoietin expression was assessed using reverse transcriptase
      polymerase chain reaction. Erythropoietin production was measured in culture
      medium using Meso Scale Discovery(r) assays. Results were plotted to compare
      different levels of production to the control. RESULTS: Cultured renal cells
      expressed high levels of erythropoietin under hypoxia for up to 24 hours with a
      gradual decrease thereafter. However, erythropoietin expression was decreased
      when cells were switched from a hypoxic to a normoxic environment within the
      initial 24 hours. This indicated that cultured renal cells have the capacity to
      sense environmental oxygen tension and regulate erythropoietin expression
      accordingly. In addition, erythropoietin release in medium followed a pattern
      similar to that of gene expression under normoxic and hypoxic conditions.
      CONCLUSIONS: These findings indicate that primary renal cells have the ability to
      regulate erythropoietin gene expression and release through environment dependent
      mechanisms. This also suggests that with further study the possibility exists of
      developing these cells as a potential method to treat renal failure induced
      anemia.

PMID- 22999550
TI  - Caffeine ingestion causes detrusor overactivity and afferent nerve excitation in
      mice.
AB  - PURPOSE: We examined the effect of caffeine (Sigma(r)) on voiding patterns in
      mice and characterized potential changes in bladder function and sensory
      signaling. MATERIALS AND METHODS: A total of 12 mice were fed high dose (150
      mg/kg) caffeine daily for 2 weeks. Micturition frequency and volume were recorded
      at baseline and at the end point. The effects of chronic low dose (10 mg/kg)
      caffeine on voiding patterns were examined in 7 mice, which were subsequently
      studied using awake cystometry. In a separate study to characterize the effects
      of acute caffeine consumption on bladder function and sensory signaling
      cystometry was performed in 6 mice. Bladder extracellular multifiber afferent
      signaling was recorded at baseline and 1 hour after feeding low dose caffeine. In
      a separate group of mice baseline cystometrograms were done using normal saline,
      followed by a caffeine filling solution. RESULTS: Compared to pretreatment
      conditions, daily oral high dose caffeine resulted in a significant increase in
      average micturition frequency and a decreased average volume per void. In animals
      fed low dose caffeine cystometry demonstrated a statistically significant
      increase in filling and threshold bladder pressure compared to caffeine naive
      animals. Acute low dose caffeine ingestion resulted in a significant increase in
      filling pressure, an increased frequency of nonvoiding bladder contractions, a
      decrease in cystometric capacity and a 7.2-fold increase in the average firing
      rate of afferent nerves during filling. Caffeine administered intravesically had
      no effect on cystometric parameters. CONCLUSIONS: Oral caffeine administration
      results in detrusor overactivity and increased bladder sensory signaling in the
      mouse.

PMID- 22999551
TI  - Prostate MRI: the hemorrhage exclusion sign.

PMID- 22999552
TI  - Testicular fibroma.

PMID- 22999553
TI  - Re: Does low intensity extracorporeal shock wave therapy have a physiological
      effect on erectile function? Short-term results of a randomized, double-blind,
      sham controlled study: Y. Vardi, B. Appel, A. Kilchevsky and I. Gruenwald. J Urol
      2012; 187: 1769-1775.

PMID- 22999554
TI  - Endometrial expression of selected genes in patients achieving pregnancy
      spontaneously or after ICSI and patients failing at least two ICSI cycles.
AB  - The objective of this study was to identify the endometrial gene expression
      profile in receptive phase, which could represent a useful prognostic tool for
      selecting IVF patients. Endometrial expression of 47 selected genes biopsied
      during the window of implantation in natural cycles was compared between patients
      who achieved a successful pregnancy spontaneously or after subsequent
      intracytoplasmic sperm injection (ICSI) cycles and patients who did not achieve a
      pregnancy after at least two failed ICSI cycles. The comparative analysis showed
      significantly different levels of expression in 19 genes, five implicated in
      apoptosis (CASP8, FADD, CASP10, APAF1, ANXA4), three in immunity (LIF, SPP1,
      C4BPA), five in transcriptional activity (MSX1, HOXA10, MSX2, HOXA11, GATA2), two
      in lipid metabolism (LEPR, APOD) and four in oxidative metabolism (AOX1, ALDH1A3,
      GPX3, NNMT). The evidence for these genes being differently expressed could
      represent the starting point of identifying the ideal receptive endometrial gene
      expression profile, which could be used in the future as a prognostic tool for
      IVF patients. Gene expression analysis technology has opened new important
      perspectives on the study of the physiological processes of different tissues and
      organs. Specifically for the endometrium, it would be really interesting to find
      out an endometrial gene expression profile of receptive phase, which could be
      used in future as a useful prognostic tool for selecting IVF patients. To achieve
      this aim, the objective of the present paper was the comparison of endometrial
      expression in natural cycles of 47 selected genes between the biopsies of
      patients who achieved a successful pregnancy, either spontaneously or after
      subsequent ICSI cycles, and those of patients who did not achieve a pregnancy
      after at least two failed ICSI cycles. The comparative analysis showed a
      significant different expression in 19 genes: five implicated in programmed cell
      death, known as apoptosis (CASP8, FADD, CASP10, APAF1, ANXA4), three in immunity
      (LIF, SPP1, C4BPA), five in transcriptional activity (MSX1, HOXA10, MSX2, HOXA11,
      GATA2), two in lipid metabolism (LEPR, APOD) and four in oxidative metabolism
      (AOX1, ALDH1A3, GPX3, NNMT). The evidence of these genes being differently
      expressed could represent the starting point of identifying the ideal receptive
      endometrial gene expression profile which could be used in the future as a
      prognostic tool for IVF patients.

PMID- 22999555
TI  - Effects of transdermal testosterone in poor responders undergoing IVF: systematic
      review and meta-analysis.
AB  - A systematic review and meta-analysis was performed to evaluate the effect of
      transdermal testosterone preceding ovarian stimulation in women with poor ovarian
      response undergoing IVF. Studies comparing pretreatment with transdermal
      testosterone versus standard ovarian stimulation among poor responders were
      included. The main outcome assessed was live birth. Three trials were included
      (113 women in the testosterone group, 112 in the control group). Testosterone
      treated women achieved significantly higher live birth rate (risk ratio, RR,
      1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to
      3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82
      to -312.09). However, differences observed in clinical pregnancy per embryo
      transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). No
      differences were observed regarding number and quality of the oocytes retrieved.
      In conclusion, transdermal testosterone significantly increases live birth and
      reduces the doses of FSH required. These findings support the theoretical
      synergistic role of androgens and FSH on folliculogenesis. The present data
      should be interpreted with caution because of the small number of trials and
      clinical heterogeneity. The identification of poor responders that could
      especially benefit from testosterone treatment should be addressed in further
      studies. The poor response to ovarian stimulation among women undergoing IVF is
      of great concern in reproductive medicine. Certain modalities have been tested to
      improve this response to gonadotrophin stimulation, although results from some
      studies have shown conflicting results. Hence, a systematic review and meta
      analysis was performed in order to evaluate the effect of transdermal
      testosterone prior to ovarian stimulation among these women with poor ovarian
      response. The main outcome assessed was live birth rate. In all, three trials
      were included, which comprehended 113 women in the testosterone group and 112 in
      the control group. Women that were pretreated with transdermal testosterone
      achieved significantly higher live birth rate and clinical pregnancy rate and
      required significantly lower doses of exogenous FSH as compared with controls.
      However, when clinical pregnancy rate was adjusted per embryo transferred
      differences observed were not statistically significant. No differences were
      observed in the number and quality of the oocytes retrieved. In conclusion,
      transdermal testosterone prior to ovarian stimulation significantly increases
      live birth and reduces the doses of FSH required among poor responders. In
      addition, the identification of poor responders that could especially benefit
      from testosterone treatment should be addressed in further studies.

PMID- 22999556
TI  - Association of CLOCK gene variants with semen quality in idiopathic infertile Han
      Chinese males.
AB  - Recent experimental animal studies suggested that the circadian locomotor output
      cycles kaput protein gene (CLOCK) may play an important role in male
      reproduction. So far, such data for humans are not available. This study used
      single-nucleotide polymorphisms (SNP) to examine the association between CLOCK
      and semen quality in a human population with idiopathic infertility. Three
      variant genotyping of CLOCK and semen analysis were performed in 478 men with
      idiopathic infertility by SNP genotyping assays and computer-aided sperm
      analysis. Subjects carrying a C allele at rs3749474 (CC and TC) presented
      significantly lower semen volume (P=<0.001 and 0.001, respectively) compared with
      the TT genotype. Subjects carrying the rs3749474 CC genotype had significantly
      lower sperm number per ejaculate (P=0.026) and sperm motility (P=0.021) than TT
      genotype carriers. rs1801260 TC genotype carriers had significantly lower sperm
      motility compared with the TT genotype (P=0.028). For the rs3817444 genotypes, CA
      and AA genotype carriers presented significantly lower semen volume compared with
      the CC genotype (P=0.022 and 0.001, respectively). The findings suggest, as far
      as is known for the first time, an association between CLOCK genetic variants and
      altered semen quality in a human population with idiopathic infertility. The gene
      encoding the circadian locomotor output cycles kaput protein (CLOCK) functions as
      an important positive enhancer of the circadian system. The observations reported
      in recent experimental animal studies suggested that CLOCK may play an important
      role in male reproduction. So far, such data for humans are not available. In
      this study, single-nucleotide polymorphisms (SNP) were used to examine the
      association between CLOCK and semen quality in human population with idiopathic
      infertility. Three-variant genotyping of CLOCK and semen analysis were performed
      in 478 males with idiopathic infertility by SNP genotyping assays and computer
      assisted semen analysis. The results showed that the subjects carrying a C allele
      at rs3749474 (CC and TC) presented significantly lower semen volume compared with
      the TT genotype. For subjects carrying the CC genotype, sperm number per
      ejaculate and sperm motility were significantly lower compared with TT genotype
      carriers. The rs1801260 TC genotype carriers also had significantly lower sperm
      motility compared with the TT genotype. For the rs3817444 genotypes, the CA and
      AA genotype carriers presented significantly lower semen volume compared with the
      CC genotype. The findings suggested, as far as is known for the first time, an
      association between CLOCK genetic variants and altered semen quality in a human
      population with idiopathic infertility.

PMID- 22999557
TI  - Apoptosis of human ovarian tissue is not increased by either vitrification or
      rapid cooling.
AB  - This study evaluated the incidence of morphological changes, as assessed by light
      microscopy, and apoptosis in vitrified and rapidly cooled human ovarian tissue.
      Apoptosis was assessed 30 min and 24h after warming using transmission electron
      microscopy, terminal deoxynucleotidyl transferase-mediated dUDP nick-end
      labelling (TUNEL) assay and DNA fragmentation, as determined by gel
      electrophoresis. The results showed no significant changes in morphology,
      chromatin condensation, DNA fragmentation or TUNEL-positive cells in follicles
      attributable to cryopreservation or exposure to the cryoprotectant solutions
      alone. In conclusion, the cryopreservation protocols did not affect the incidence
      of apoptosis and either protocol could be an alternative to slow cooling of
      ovarian tissue. This study evaluated the incidence of morphological changes, as
      assessed by light microscopy, and apoptosis in human ovarian tissue cryopreserved
      using two different methods, i.e. vitrification and rapid cooling. Apoptosis was
      assessed in tissue 30 min and 24h after warming using transmission electron
      microscopy and terminal deoxynucleotidyl transferase-mediated dUDP nick-end
      labelling (TUNEL) assay and DNA fragmentation as determined by gel
      electrophoresis. The results showed no significant changes in morphology,
      chromatin condensation, DNA fragmentation or TUNEL-positive cells in follicles
      attributable to cryopreservation or exposure to the cryopreservation solutions
      alone. In conclusion, the cryopreservation protocols did not affect the incidence
      of apoptosis in human ovarian tissue and either protocol could be an alternative
      to slow cooling for the preservation of ovarian tissue.

PMID- 22999558
TI  - Hypermyelination and overexpression of neuregulin-1 in thoracic sympathetic
      nerves in patients with primary palmar hyperhidrosis.
AB  - Primary palmar hyperhidrosis (PPH) is a condition characterized by high levels of
      palmar perspiration in excess of physiological need. The etiopathogenesis of PPH
      is thought to be related to hyperactivity of the sympathetic system, but the
      exact mechanism is still obscure. The aim of this study was to observe the
      ultrastructure of the thoracic sympathetic nerves and measure the expression of
      neuregulin-1 (Nrg-1) in thoracic sympathetic nerve tissue in patients with PPH
      relative to control subjects. Samples of T3 sympathetic ganglia were obtained
      from 58 subjects: 30 PPH patients who underwent endoscopic thoracic sympathectomy
      and 28 control subjects who underwent pleurectomy for chronic empyema. The
      ultrastructure of the myelin sheath of the sympathetic axons was observed using
      electron microscopy, and the thickness of the myelin sheath was compared between
      the two groups. Expression of Nrg-1 mRNA in thoracic sympathetic nerve tissue was
      evaluated using reverse transcription-polymerase chain reaction analysis.
      Subjects in the hyperhidrosis group had a significantly greater average myelin
      thickness and a significantly lower g-ratio relative to the control group. The
      hyperhidrosis group had significantly higher relative expression of Nrg-1 mRNA in
      thoracic sympathetic nerve tissue. Hypermyelination of the thoracic sympathetic
      axons is probably one pathogenetic mechanism underlying PPH. Nrg-1 is likely to
      be an important cause of hypermyelination in thoracic sympathetic axons in
      patients with PPH.

PMID- 22999559
TI  - Solitary juvenile xanthogranuloma mimicking intracranial tumor in children.
AB  - Juvenile xanthogranuloma (JXG) is primarily a benign cutaneous disorder of non
      Langerhans hystiocytic proliferation. Systemic involvement occurs in 4% of
      patients; isolated central nervous system (CNS) lesions are rare. We report
      solitary CNS-JXG lesions in two patients. A 3.5-year-old boy with a parietal
      occipital lesion underwent total resection with no surgical morbidity and no
      recurrence at 16-month follow-up. A 3.5-year-old girl underwent subtotal
      resection of a tumor extending from the left Meckel's cave and invading the
      cavernous sinus and left orbit with extensive cranial nerve involvement. Tumor
      regrowth with leptomeningeal spread at 9-month and 12-month follow-up was managed
      with steroids and chemotherapy (vinblastine and later cladribine). We present our
      experience and review the literature pertaining to rare reports of solitary CNS
      JXG.

PMID- 22999560
TI  - Idiopathic hypereosinophilic syndrome revealed by encephalopathy.
AB  - Idiopathic hypereosinophilic syndrome (HES) is characterized by persistent
      hypereosinophilia ( >= 1500/mm(3)) with evidence of end-organ damage without a
      definite underlying cause. Hypereosinophilia-induced encephalopathy is a rare
      clinical syndrome. We present a male patient with idiopathic HES with distinctive
      encephalopathy who had hypereosinophilia for more than 6 months. Eosinophils in
      repeated blood tests were more than 1500/mm(3). He had hematological, brain, bone
      marrow, and possible cardiac involvement. Although numerous efforts were made to
      identify the underlying cause of hypereosinophilia, specific causes could not be
      found in this patient. Bone-marrow analysis confirmed the diagnosis. The unique
      features were the prominent involvement of the cerebral cortex and the dramatic
      response to steroids with marked improvement of eosinophilia and brain function.
      The mechanisms of hypereosinophilia-induced encephalopathy are discussed.

PMID- 22999561
TI  - Relationship of the location of the ventricular catheter tip and function of the
      ventriculoperitoneal shunt.
AB  - The long-term maintenance of ventriculoperitoneal (VP) shunt function depends on
      the correct placement of the catheter tip in the lateral ventricle. The
      relationship between the location of the ventricular catheter tip and VP shunt
      function was analyzed in 52 patients. The location of the ventricular catheter
      tip was classified into one of the following five groups: (i) Group A--superior
      to the foramen of Monro; (ii) Group B--in the center of the lateral ventricle
      body; (iii) Group C--in the third ventricle; (iv) Group D--contacting the
      ventricle wall; and (v) Group E--in the septum pellucidum. VP shunt function was
      defined as well controlled hydrocephalus when the Evan's ratio of the ventricular
      size was < 0.3. The VP shunt functioned well in 14 of 52 patients (26.9%), the
      shunt valve pressure was incorrectly set in 21 (40.4%), and irreversible shunt
      malfunction was identified in 17 (32.7%). Among the 14 patients with a well
      functioning shunt, 13 were in Groups A or B with an odds ratio (OR) of 17.875
      (p<0.05). In the 17 irreversible shunt malfunctions, 13 were identified in Groups
      C, D, or E with an OR of 0.123 (p<0.05). Long term VP shunt function or failure
      due to irreversible malfunction is directly influenced by the position of the
      ventricular catheter tip. Ideal points for positioning the ventricular catheter
      tip are superior to the foramen of Monro and in the center of the lateral
      ventricle body. Early shunt revision may be required for patients in whom the
      catheter tip contacts the ventricle wall or is located in the septum pellucidum.

PMID- 22999562
TI  - Regulation of glycogen synthase kinase-3 beta (GSK-3beta) by the Akt pathway in
      gliomas.
AB  - Gliomas are aggressive brain tumours that, despite advances in multimodal
      therapies, continue to portend a dismal prognosis. Glioblastoma multiforme (GBM)
      represents the most aggressive glioma and patients have a median survival of 14
      months, even with the best available treatments. The phosphoinositide 3
      kinase/Akt/glycogen synthase kinase-3 beta (GSK-3beta) and Wnt/beta-catenin
      pathways are dysregulated in a number of cancers, and these two pathways share a
      common node protein, GSK-3beta. This protein is responsible for the
      regulation/degradation of beta-catenin, which reduces beta-catenin's
      translocation to the nucleus and influences the subsequent transcription of
      oncogenes. The non-specific small-molecule GSK-3beta inhibitor, lithium chloride
      (LiCl), and the specific Akt inhibitor, AktX, were used to treat U87MG and
      U87MG.Delta2-7 human glioma cell lines. LiCl treatment significantly affected
      cell morphology of U87MG and U87MG.Delta2-7 cells, while also increasing levels
      of phospho-GSK-3beta in a dose-dependent manner. Increased cell proliferation was
      observed at low-to-mid LiCl concentrations as determined by MTT cell growth
      assays. Treatment of U87MG and U87MG.Delta2-7 cells with AktX resulted in reduced
      levels of phospho-GSK-3beta through its inhibition of Akt, in addition to
      decreased levels of phosphorylated (active) Akt in a dose-dependent fashion. We
      have shown in this study that GSK-3beta regulation by phosphorylation is
      important for cell morphology and growth, and that LiCl enhances growth of U87MG
      and U87MG.Delta2-7 cells by inhibiting GSK-3beta through its phosphorylation,
      whereas AktX reduces growth via activation of GSK-3beta by inhibiting Akt's
      kinase activity.

PMID- 22999563
TI  - Capsular warning syndrome and crescendo lacunar strokes after atherosclerotic
      stenosis of the recurrent artery of Heubner.
AB  - The stereotype of repetitive transient cerebral ischemia causing unilateral
      motor, sensory, or sensorimotor deficits that simultaneously affect the face,
      arm, and leg, clinically localized to the internal capsule, fits with the
      description of capsular warning syndrome (CWS). A high proportion of individuals
      with these symptoms develop subsequent capsular stroke, despite various proposed
      preventative measures. It has been postulated that the mechanism for such strokes
      is that of small-vessel single-penetrator disease. We present a patient with
      repetitive CWS intermingled with crescendo capsular strokes secondary to
      recurrent artery of Heubner disease. This report causally links CWS-crescendo
      lacunar strokes and Heubner artery atherosclerotic disease (intracranial branch
      atheromatous disease).

PMID- 22999564
TI  - Familial Creutzfeldt-Jakob disease with a mutation at codon 180 presenting with
      an atypical phenotype.
AB  - The clinical features of familial Creutzfeldt-Jakob disease (fCJD) with a
      mutation at codon 180 (V180I) are less typical than those of patients with
      sporadic CJD. We describe a patient with pathologically confirmed CJD carrying
      the V180I mutation who had atypical cerebrospinal fluid and
      electroencephalography findings. Similar to other prion protein mutations, this
      report suggests that the V180I mutation is not the exclusive determinant of the
      phenotype.

PMID- 22999565
TI  - The New Zealand Neuromuscular Disease Registry.
AB  - The development of effective treatments for neuromuscular diseases is a
      significant challenge due to difficulties in identifying adequate numbers of
      patients for clinical trials. Low patient numbers in these rare diseases also has
      an effect when establishing sound clinical practices based on experience gained
      from patients with similar diagnosis. The Muscular Dystrophy Association of New
      Zealand (MDA), working in consort with interested clinicians has established the
      New Zealand Neuromuscular Disease (NZ NMD) Registry in order to help address
      these problems. The NZ NMD Registry is exceptional in that it comprises one
      registry for all neuromuscular conditions and will significantly benefit both
      patients with neuromuscular disease and their clinicians.

PMID- 22999566
TI  - Novel FUS mutation in patients with sporadic amyotrophic lateral sclerosis and
      corticobasal degeneration.
AB  - We report a patient with sporadic amyotrophic lateral sclerosis (ALS) with a
      novel fusion in malignant liposarcoma (FUS) gene mutation whose neurological
      signs were conspicuous left-sided rigidity and apraxia. A novel heterozygous
      guanine (G)-to-thymine (T) transition at position 1392, c.1392G>T, leading to a
      methionine-to-isoleucine substitution (p.Met464Ile), was found in exon13 of FUS.
      Re-sequencing of the genes for superoxide dismutase 1 (SOD1) and transactive
      response-DNA binding protein (TARDBP) revealed no mutations. The present findings
      suggest that this novel FUS mutation (p.Met464Ile) is related to manifestations
      of ALS as well as clinical features of corticobasal degeneration.

PMID- 22999567
TI  - Clinical utility of vagus nerve stimulation for progressive myoclonic epilepsy.

PMID- 22999568
TI  - Evaluation of inactive adults' ability to maintain a moderate-intensity walking
      pace.
AB  - OBJECTIVES: To determine self-selected brisk walking pace in currently inactive
      adults and investigate the efficacy of rhythmic auditory stimuli to regulate
      moderate intensity walking. DESIGN: A single-sample controlled laboratory design.
      METHODS: Currently inactive adults (N=25; 76% female; age=34+/-13yr) completed a
      moderate intensity treadmill walking trial, during which cadence and steady-state
      O2 were measured. Participants then completed a 10-min self-paced "brisk" walk
      followed by a 10-min moderate-paced walk, prompted by a clip-on metronome matched
      to the treadmill cadence. Data were analyzed using RM t-test, Cohen's d, Bland
      Altman plot, and one-way RM ANOVA. RESULTS: Mean energy expenditure and cadence
      during the treadmill trial were 3.88+/-0.53METs and 114+/-8stepsmin(-1). During
      self-paced brisk walking cadence was 124+/-8stepsmin(-1). Cadence during
      metronome-paced walking was slower for all participants (114+/-8stepsmin(-1);
      p<0.05, d=1.23). From the Bland-Altman plots, 23 participants walked within +/
      3stepsmin(-1) of the metronome cadence, and the other 2 participants were within
      +/-10stepsmin(-1). There were no significant differences (p>0.05) among the
      minute-by-minute cadences across the 10min of either condition. CONCLUSIONS:
      Energy expenditure during 2.7mph treadmill walking was higher than 3 METs.
      Inactive adults walk at a higher cadence during "brisk" walking, compared to
      walking at a metronome-guided moderate pace. While the natural walking pace of
      inactive adults was at an intensity known to produce health benefits, and was
      maintained for 10min, the use of rhythmic auditory feedback is an effective
      method for regulating walking at a prescribed intensity in inactive adults.

PMID- 22999575
TI  - Access to subspecialty care: bringing back the specialty of general pediatrics.

PMID- 22999574
TI  - Attempt to increase the transparency of fourth hurdle implementation in Central
      Eastern European middle income countries: publication of the critical appraisal
      methodology.
AB  - BACKGROUND: In middle income countries the number of trained health technology
      assessment specialists is limited and the public budget for health technology
      assessment is considerably lower compared to developed countries. These countries
      therefore must develop their own solutions to improve the quality and efficiency
      of health technology assessment implementation in reimbursement decisions. Our
      study aimed to develop a scientifically rigorous and detailed appraisal checklist
      for economic evaluations of pharmaceuticals in the single health technology
      assessment process. METHODS: The research design entailed a review of economic
      evaluations, submitted for reimbursement of pharmaceuticals, by two independent
      academic reviewers to identify the most common methodological problems. Fifty
      economic evaluations submitted in 2007-2008, randomly selected by the Health
      Technology Assessment Office served as data sources. The new checklist was
      developed by an iterative working process: first by assessing ten economic
      evaluations, then improving the checklist by generating new question items, then
      employing the improved checklist to assess the next ten economic evaluations.
      After appraising 25 documents, the reviewers reconciled their opinions and
      improved the checklist with the researchers of the Health Technology Assessment
      Office during an expert panel discussion. The reviewers scrutinized the second 25
      economic evaluations, after which the expert panel finalized the checklist with
      consensus. RESULTS: The final checklist consists of 91 yes or no questions in 11
      main topics concerning comparator selection, efficacy, effectiveness, costs,
      sensitivity analysis, methodological approach, transparency, and interpretation
      of results. The new checklist is based on current Hungarian evaluation practice.
      As the published checklist will be part of the official single health technology
      assessment process of pharmaceuticals, submitters will be able to assure the
      quality of their economic evaluation. CONCLUSIONS: The transparent critical
      appraisal method should improve the consistency of pharmaceutical reimbursement
      decisions and facilitate the utilization of economic evaluations in other fields
      of health care decision-making in other Central-Eastern European countries.

PMID- 22999576
TI  - 50 years ago in The Journal of Pediatrics: a study of premature infants fed cold
      formula.

PMID- 22999577
TI  - 50 years ago in The Journal of Pediatrics: a study of techniques of preparation
      of formulas for infant feeding.

PMID- 22999578
TI  - 50 years ago in The Journal of Pediatrics: the effect of degree of hypoxia on the
      electroencephalogram in infants.

PMID- 22999579
TI  - 50 years ago in The Journal of Pediatrics: treatment of excessive height in
      girls: a longitudinal study.

PMID- 22999580
TI  - 50 years ago in The Journal of Pediatrics: the surgical management of
      meningoceles and meningomyeloceles.

PMID- 22999588
TI  - Ethylene-induced overproduction of reactive oxygen species is responsible for the
      development of watersoaking in immature cucumber fruit.
AB  - Watersoaking is an ethylene-induced disorder observed in some members of the
      Cucurbitaceae including cucumber (Cucumis sativus L.), watermelon (Citrullus
      lanatus Thunb. Matsum and Nakai), and tropical pumpkin (Cucurbita moschata
      Duch.). Previous studies have found that immature beit-alpha cucumber (cv. Manar)
      exhibit watersoaking after 6d of continuous exposure to 10 MULL(-1) ethylene in
      air (21 kPa O(2)). The present study was designed to investigate the early
      dynamics of ethylene responses in immature cucumber fruit in order to provide
      insight into the watersoaking triggering mechanism. Changes in respiration,
      epidermal color, firmness, reactive oxygen species (ROS) production and
      electrolyte leakage were evaluated as a function of time under different ethylene
      concentrations and exposure duration. Ethylene concentrations exceeding 10 MULL(
      1) did not accelerate changes in any of the evaluated responses. The first
      detectable change was a significant rise in respiration on day 2, followed by a
      significant rise in ROS on day 4, and significant degreening, mesocap softening,
      and increased electrolyte leakage on day 6; the latter responses coincident with
      incipient watersoaking. Varying the duration of exposure to ethylene indicated
      that the critical exposure time is between 2 and 4d. Notably, all deleterious
      responses to ethylene were suppressed under a hypoxic atmosphere. A model is
      proposed in which ethylene induces a sharp increase in respiration with a
      concomitant sharp rise in ROS, which the immature fruit is incapable of
      quenching. The resulting production of excess ROS leads to discoloration and
      membrane deterioration, leading to the release of cytoplasmic content, rapid
      softening, and the visual symptom of watersoaking.

PMID- 22999589
TI  - Application of bronchoscopic argon plasma coagulation in the treatment of
      tumorous endobronchial tuberculosis: historical controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      bronchoscopic argon plasma coagulation for tumorous endobronchial tuberculosis.
      METHODS: We analyzed the records of 115 patients with tumorous endobronchial
      tuberculosis who did not show luminal narrowing of the bronchus at diagnosis. Of
      these 115 patients, 41 patients received bronchoscopic argon plasma coagulation
      plus routine antituberculosis chemotherapy (argon plasma coagulation group) and
      the other 74 patients received only routine antituberculosis chemotherapy
      (chemotherapy group). The treatment effects between these 2 groups were compared
      based on changes in lesions, rate of lesion disappearance, and complications
      associated with bronchoscopic argon plasma coagulation. RESULTS: The complete
      removal rate was 100% in patients in argon plasma coagulation group. About 84.6%
      lesions disappeared completely in patients in the chemotherapy group. The rate of
      disappearance of lesions in the argon plasma coagulation group was faster than
      that of the chemotherapy group. There were no severe complications in the argon
      plasma coagulation group. CONCLUSIONS: Bronchoscopic argon plasma coagulation can
      accelerate the healing of tumorous endobronchial tuberculosis and can help
      prevent progressive bronchial stenosis resulting from tumorous endobronchial
      tuberculosis, and it is a very safe method.

PMID- 22999590
TI  - The impact of incision biopsy in plastic surgery management of skin lesions.

PMID- 22999592
TI  - Long-term follow-up of microvascular free tissue transfer for mobilization of
      congenital radioulnar synostosis.

PMID- 22999591
TI  - Giant cell tumour of bone: reconstruction of the index metacarpophalangeal joint
      with an osteochondral graft from the lateral femoral condyle.
AB  - We describe the successful reconstruction of the index finger metacarpophalangeal
      joint with an osteochondral autograft from the lateral femoral condyle following
      failed curettage and cementation of a giant cell tumour of the proximal phalanx
      base. At the 2-year follow-up, a good functional outcome was noted with 0-80
      degrees  range of motion of the metacarpophalangeal joint and no clinical or
      radiographic evidence of tumour recurrence.

PMID- 22999593
TI  - Duodenal lymphoid nodularity in common variable immunodeficiency.

PMID- 22999594
TI  - MiroCam capsule for obscure gastrointestinal bleeding: a prospective, single
      centre experience.
AB  - BACKGROUND: Capsule endoscopy is an established tool for the evaluation of
      obscure gastrointestinal bleeding but published literature is mostly limited to
      PillCam SB (Given Imaging, Israel). AIMS: The aims of this study were to
      determine the findings, the diagnostic yield and the rebleeding rate in a series
      of patients with overt or occult obscure gastrointestinal bleeding studied with
      MiroCam(Intromedic, Seoul, Korea) capsule endoscopy. METHODS: Data of 118
      patients who underwent capsule endoscopy for overt or occult obscure
      gastrointestinal bleeding were prospectively collected between March 2009 and
      March 2011. RESULTS: Evaluation of the entire small bowel (completion rate) was
      achieved in 96% of cases. Relevant lesions occurred in 58% of patients.
      Angiodysplasias was the most common finding. Six patients (9% of the positive
      findings) had a non-small-bowel lesion detected by capsule. The yield of capsule
      endoscopy in the overt group was greater than in the occult group but without
      achieving a significant difference (61% vs. 54%, p>0.05). Rebleeding rate was
      lower in patients with a negative examination (6%) than in patients with a
      positive one (17%) (p=0.03). Capsule retention was registered in 3 of 118
      patients (2.5%). CONCLUSIONS: MiroCam capsule endoscopy is a safe and effective
      tool for exploring small bowel with a high completion rate.

PMID- 22999596
TI  - Immediate sequential bilateral cataract surgery.

PMID- 22999595
TI  - Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically
      modified maize.
AB  - The health effects of a Roundup-tolerant genetically modified maize (from 11% in
      the diet), cultivated with or without Roundup, and Roundup alone (from 0.1 ppb in
      water), were studied 2 years in rats. In females, all treated groups died 2-3
      times more than controls, and more rapidly. This difference was visible in 3 male
      groups fed GMOs. All results were hormone and sex dependent, and the pathological
      profiles were comparable. Females developed large mammary tumors almost always
      more often than and before controls, the pituitary was the second most disabled
      organ; the sex hormonal balance was modified by GMO and Roundup treatments. In
      treated males, liver congestions and necrosis were 2.5-5.5 times higher. This
      pathology was confirmed by optic and transmission electron microscopy. Marked and
      severe kidney nephropathies were also generally 1.3-2.3 greater. Males presented
      4 times more large palpable tumors than controls which occurred up to 600 days
      earlier. Biochemistry data confirmed very significant kidney chronic
      deficiencies; for all treatments and both sexes, 76% of the altered parameters
      were kidney related. These results can be explained by the non linear endocrine
      disrupting effects of Roundup, but also by the overexpression of the transgene in
      the GMO and its metabolic consequences.

PMID- 22999597
TI  - Timely cataract surgery for improved glaucoma management.

PMID- 22999598
TI  - Simplified ab externo scleral fixation for late in-the-bag intraocular lens
      dislocation.
AB  - Many surgical techniques to repair late in-the-bag intraocular lens (IOL)
      dislocation have been described. We present a modification to ab externo scleral
      fixation of in-the-bag IOL dislocation that minimizes cumbersome intraocular
      manipulations. Using an iris hook for intraocular suture retrieval under direct
      visualization eliminates the need to mate the suture needle with a hypodermic
      needle, and the site through which the hook is used provides an ideal place for
      suture knot burial, potentially minimizing late suture erosion or exposure.

PMID- 22999599
TI  - Rescue technique for salvaging toric intraocular lens alignment.
AB  - Accurate alignment of a toric intraocular lens (IOL) is a requisite to achieving
      the intended reduction in astigmatism at the time of cataract surgery. However,
      it requires a reasonably clear view of the limbal vascular anatomy, which is
      sometimes altered by chemosis from a subconjunctival anesthetic injection or a
      hemorrhage. We describe a technique that can quickly restore vascular anatomy and
      facilitate toric IOL alignment.

PMID- 22999600
TI  - Comparability and repeatability of corneal astigmatism measurements using
      different measurement technologies.
AB  - PURPOSE: To determine the comparability and repeatability of corneal astigmatism
      measurements obtained with different devices and determine the interobserver
      variability of a new automated keratometer. SETTING: University Eye Clinic
      Maastricht, the Netherlands. DESIGN: Prospective cohort study. METHODS: The right
      eye of healthy subjects was examined with the following 6 devices: IOLMaster
      (automated keratometry), Lenstar (automated keratometry), SMI Reference Unit 3
      (automated keratometry), Javal (manual keratometry), KR-1W (corneal topography),
      and Pentacam (Scheimpflug imaging). An experienced operator obtained 3 repeated
      measurements. An inexperienced operator obtained additional measurements with the
      SMI Reference Unit 3. Astigmatism vector analysis was used to determine the
      comparability, repeatability, and interobserver variability. RESULTS: Corneal
      astigmatism vectors measured by automated, manual, or simulated keratometry were
      comparable except for the Pentacam equivalent keratometry (K) (P<.001, repeated
      measures analysis of variance [ANOVA]). The mean difference between the
      equivalent K and other K values was 0.18 to 0.29 diopter (D) (P<.05, Hotelling
      trace multivariate ANOVA). The mean differences between automated, manual, and
      simulated keratometry were small (<=0.12 D). The within-subject standard
      deviation ranged from 0.05 D @ 21 degrees (KR-1W) to 0.18 D @ 23 degrees
      (Lenstar). The SMI Reference Unit showed small mean differences and comparable
      repeatability between the experienced operator and the inexperienced operator.
      CONCLUSIONS: Vector analysis showed comparable corneal astigmatism measurements
      using automated, manual, and simulated keratometry. Pentacam equivalent K values
      were not comparable with those of the other keratometers. The repeatability of
      astigmatism magnitudes was acceptable; however, the repeatability of astigmatism
      meridians was moderate. The SMI Reference Unit showed good interobserver
      variability.

PMID- 22999601
TI  - Long-term safety and visual outcomes of anterior chamber intraocular lens
      implantation in patients with a history of chronic uveitis.
AB  - PURPOSE: To compare the visual outcomes and prevalence of long-term complications
      in patients with quiescent uveitis after phacoemulsification with traditional in
      the-bag intraocular lens (IOL) implantation versus primary or secondary anterior
      chamber (AC) IOL implantation due to inadequate capsule support. SETTING: Single
      center private practice. DESIGN: Retrospective observational cohort study.
      METHODS: Patients with quiescent uveitis who had cataract surgery with subsequent
      AC IOL implantation were identified through an electronic medical record
      database. They were age matched with patients with uveitis who had conventional
      placement of a posterior chamber (PC) IOL. The rate of postoperative
      complications and corrected distance visual acuity (CDVA) were reviewed
      preoperatively and 1, 3, and 6 months and 1, 2, 3, and 4 years postoperatively.
      RESULTS: The incidence of postoperative complications was not statistically
      different for any criterion except posterior capsule opacification development in
      the PC IOL cohort (relative risk, 0.071). The mean follow-up was 36.11 months +/-
      17.3 (SD) in the AC IOL group and 53.72 +/- 20.4 months in the PC IOL group. The
      mean preoperative CDVA was 1.49 +/- 1.07 logMAR in the AC IOL group and 0.5 +/-
      0.26 logMAR in the PC IOL group. Both groups had a significant improvement in
      CDVA visual acuity 3 years postoperatively (P=.001 and P=.010 respectively).
      CONCLUSIONS: In uveitic eyes with inadequate capsule support, AC IOL implantation
      was safe and effective in providing satisfactory improved CDVA without a
      significant increase in long-term complications compared with eyes that had PC
      IOL placement.

PMID- 22999602
TI  - Transitioning from mechanical microkeratome to femtosecond laser flap creation:
      visual outcomes of an experienced and a novice LASIK surgeon.
AB  - PURPOSE: To compare the visual outcomes of the first 200 myopic laser in situ
      keratomileusis (LASIK) cases between a mechanical microkeratome expert surgeon
      and a fellowship-trained surgeon transitioning to the femtosecond laser. SETTING:
      London Vision Clinic, London, United Kingdom. DESIGN: Comparative case series.
      METHODS: This analysis comprised the first 200 consecutive myopic LASIK
      procedures using the Visumax femtosecond laser and the MEL 80 excimer laser for
      an expert surgeon (11,637 previous microkeratome LASIK procedures) and a
      fellowship-trained surgeon (observed 1057, performed 155 supervised LASIK
      procedures) following a standardized surgical technique. Inclusion criteria were
      preoperative spherical equivalent (SE) refraction up to -8.50 diopters (D),
      cylinder up to 3.50 D, and corrected distance visual acuity (CDVA) of 20/20 or
      better. Follow-up was 1 year. RESULTS: There were no statistically significant
      differences in outcome measures between surgeons. Preoperatively, the mean SE was
      -4.00 D +/- 1.83 (SD) and -3.97 +/- 1.98 D and the mean cylinder was 0.81 +/-
      0.67 D and 0.79 +/- 0.66 D for the expert surgeon and fellowship-trained surgeon,
      respectively. Postoperatively, the SE was +/-0.50 D in 79% and 74%, uncorrected
      distance visual acuity was 20/20 or better in 96% and 96%, and 1 line of CDVA was
      lost in 3.5% and 1.5% for the expert surgeon and fellowship-trained surgeon,
      respectively. Contrast sensitivity increased or was unchanged. CONCLUSION: A
      fellowship-training program based on a standardized surgical protocol resulted in
      statistically comparable outcomes between an expert surgeon and a fellowship
      trained surgeon when newly transitioned to a femtosecond laser device.

PMID- 22999603
TI  - Etiology of surface light scattering on hydrophobic acrylic intraocular lenses.
AB  - PURPOSE: To study the etiology of surface light scattering on hydrophobic acrylic
      intraocular lenses (IOLs). SETTING: Alcon Research Laboratories, Fort Worth,
      Texas, USA. DESIGN: Experimental study. METHODS: Intraocular lenses were obtained
      from clinical explantations (n = 5), from human cadavers (n = 8), and from
      finished-goods inventory (controls). Surface light scattering was measured and
      imaged with the IOLs in various hydration states (dry, short-term wetted, and
      long-term hydrated) before and after proteins were quantified and removed.
      Selected IOL samples were analyzed with x-ray photoelectron spectroscopy,
      scanning electron microscopy (SEM) with energy-dispersion x-ray analysis, Fourier
      transform infrared spectroscopy with attenuated total reflectance, and cryogenic
      SEM with a focused ion beam. RESULTS: No inorganic deposits or organic changes
      were observed on any IOL surface. Under clinically relevant hydrated conditions,
      surface light-scattering intensity was independent of proteinaceous biofilm state
      (P>=.11). Instead, the hydration state of the IOLs significantly contributed to
      the intensity of surface light scattering (P<.001); clinically explanted and
      cadaver-eye IOLs (but not control IOLs) exhibited minimal scatter when dry,
      intermediate scatter when wetted, and maximum scatter when hydrated. Subsurface
      nanoglistenings with diameters less than a micron and with locations up to 120
      MUm from the surface of the IOLs were characterized by SEM with a focused ion
      beam and were identified as the source of the hydration-related surface light
      scattering. CONCLUSION: Surface light scattering on hydrophobic IOLs was
      predominantly caused by hydration-related subsurface nanoglistenings within the
      acrylic IOL material.

PMID- 22999604
TI  - Mixed Acanthamoeba and multidrug-resistant Achromobacter xyloxidans in late-onset
      keratitis after laser in situ keratomileusis.
AB  - A 31-year-old woman developed a spontaneous flap interface keratitis in the left
      eye 6 years after a laser in situ keratomileusis (LASIK) enhancement. Cultures
      and polymerase chain reaction (PCR) were positive for Achromobacter xyloxidans
      resistant to first- and second-generation cephalosporin, aminoglycosides, and
      quinolones and also positive for Acanthamoeba T4. Treatment with topical
      fortified ceftazidime, topical chlorhexidine, and voriconazole and oral
      voriconazole did not stop the progression of the disease. Flap amputation
      revealed persistence of Acanthamoeba but not Achromobacter. Six weeks after flap
      amputation, the infiltrate had resolved, PCR was negative for Acanthamoeba, and
      the cornea had fully epithelialized. To our knowledge, this is the first report
      of post-LASIK infectious keratitis caused by mixed infection of Achromobacter
      xyloxidans and Acanthamoeba occurring years after the procedure without apparent
      ocular trauma. It is also the first report of the use of combined systemic and
      topical voriconazole as a therapy for Acanthamoeba keratitis after LASIK.

PMID- 22999605
TI  - Fibrin glue for prevention of recurrent epithelial ingrowth under a LASIK flap
      with a central buttonhole defect.
AB  - A 61-year-old woman presented with a paracentral buttonhole flap defect
      associated with a linear tear, extensive epithelial ingrowth, and macrostriae in
      the right eye. A laser in situ keratomileusis enhancement had been performed 3
      weeks earlier. The epithelial ingrowth was removed after careful lifting of the
      flap, and tissue adhesive was used postoperatively as a barrier to further
      ingrowth. Six months postoperatively, the patient's corrected distance visual
      acuity had improved to 20/20 and the slitlamp examination showed no evidence of
      recurrent epithelial ingrowth. This case presents a novel approach to the
      management of a buttonhole defect.

PMID- 22999606
TI  - Acute-onset cataract as the initial presentation of diabetes mellitus.
AB  - Cataract is a well-recognized complication of diabetes mellitus (DM). The onset
      varies, although the appearance commonly follows the initial DM diagnosis. We
      describe a case of a young man who presented with bilateral acute-onset cataract
      with good general health and no prior ocular symptoms. We also discuss
      considerations for surgical planning in this case.

PMID- 22999607
TI  - Effect of corrected distance visual acuity on intraocular lens power prediction
      accuracy.

PMID- 22999608
TI  - Safety of besifloxacin ophthalmic suspension 0.6% in cataract surgery patients.

PMID- 22999610
TI  - Cataract surgical problem: October consultation.

PMID- 22999620
TI  - Caution essential in quick-pull technique.

PMID- 22999621
TI  - Capsulorrhexis rescue techniques.

PMID- 22999623
TI  - Cataract surgery evaluation tool.

PMID- 22999624
TI  - Complications related to the explantation of cosmetic iris implants.

PMID- 22999627
TI  - Combination of corneal crosslinking and intrastromal corneal ring segments for
      the treatment of keratoconus.

PMID- 22999628
TI  - Paradoxical central corneal steepening after collagen crosslinking in a case with
      intrastromal corneal ring segments.

PMID- 22999629
TI  - Multifocal IOLs as a low vision aid in eyes with AMD.

PMID- 22999630
TI  - Peripheral keratitis following low-pulse energy femtosecond laser in situ
      keratomileusis.

PMID- 22999631
TI  - Incorrect application of the clinical history method.

PMID- 22999632
TI  - [Transfusion serious adverse events and root cause analysis].

PMID- 22999633
TI  - Alteration of astrocytes and Wnt/beta-catenin signaling in the frontal cortex of
      autistic subjects.
AB  - BACKGROUND: Autism is a neurodevelopmental disorder characterized by impairments
      in social interaction, verbal communication and repetitive behaviors. To date the
      etiology of this disorder is poorly understood. Studies suggest that astrocytes
      play critical roles in neural plasticity by detecting neuronal activity and
      modulating neuronal networks. Recently, a number of studies suggested that an
      abnormal function of glia/astrocytes may be involved in the development of
      autism. However, there is yet no direct evidence showing how astrocytes develop
      in the brain of autistic individuals. METHODS: Study subjects include brain
      tissue from autistic subjects, BTBR T + tfJ (BTBR) and Neuroligin (NL)-3 knock
      down mice. Western blot analysis, Immunohistochemistry and confocal microscopy
      studies have be used to examine the density and morphology of astrocytes, as well
      as Wnt and beta-catenin protein expression. RESULTS: In this study, we
      demonstrate that the astrocytes in autisitcsubjects exhibit significantly reduced
      branching processes, total branching length and cell body sizes. We also detected
      an astrocytosis in the frontal cortex of autistic subjects. In addition, we found
      that the astrocytes in the brain of an NL3 knockdown mouse exhibited similar
      alterations to what we found in the autistic brain. Furthermore, we detected that
      both Wnt and beta-catenin proteins are decreased in the frontal cortex of
      autistic subjects. Wnt/beta-catenin pathway has been suggested to be involved in
      the regulation of astrocyte development. CONCLUSIONS: Our findings imply that
      defects in astrocytes could impair neuronal plasticity and partially contribute
      to the development of autistic-like behaviors in both humans and mice. The
      alteration of Wnt/beta-catenin pathway in the brain of autistic subjects may
      contribute to the changes of astrocytes.

PMID- 22999634
TI  - Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred
      laser treatment: three-year randomized trial results.
AB  - OBJECTIVE: To report the 3-year follow-up results within a previously reported
      randomized trial evaluating prompt versus deferred (for >=24 weeks) focal/grid
      laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic
      macular edema (DME). DESIGN: Multicenter, randomized clinical trial.
      PARTICIPANTS: Three hundred sixty-one participants with visual acuity of 20/32 to
      20/320 (approximate Snellen equivalent) and DME involving the fovea. METHODS:
      Ranibizumab every 4 weeks until no longer improving (with resumption if
      worsening) and random assignment to prompt or deferred (>=24 weeks) focal/grid
      laser treatment. MAIN OUTCOME MEASURES: Best-corrected visual acuity and safety
      at the 156-week (3-year) visit. RESULTS: The estimated mean change in visual
      acuity letter score from baseline through the 3-year visit was 2.9 letters more
      (9.7 vs. 6.8 letters; mean difference, 2.9 letters; 95% confidence interval, 0.4
      5.4 letters; P = 0.02) in the deferral group compared with the prompt laser
      treatment group. In the prompt laser treatment group and deferral group,
      respectively, the percentage of eyes with a >=10-letter gain/loss was 42% and 56%
      (P = 0.02), whereas the respective percentage of eyes with a >=10-letter
      gain/loss was 10% and 5% (P = 0.12). Up to the 3-year visit, the median numbers
      of injections were 12 and 15 in the prompt and deferral groups, respectively (P =
      0.007), including 1 and 2 injections, respectively, from the 2-year up to the 3
      year visit. At the 3-year visit, the percentages of eyes with central subfield
      thickness of 250 MUm or more on time-domain optical coherence tomography were 36%
      in both groups (P = 0.90). In the deferral group, 54% did not receive laser
      treatment during the trial. Systemic adverse events seemed to be similar in the 2
      groups. CONCLUSIONS: These 3-year results suggest that focal/grid laser treatment
      at the initiation of intravitreal ranibizumab is no better, and possibly worse,
      for vision outcomes than deferring laser treatment for 24 weeks or more in eyes
      with DME involving the fovea and with vision impairment. Some of the observed
      differences in visual acuity at 3 years may be related to fewer cumulative
      ranibizumab injections during follow-up in the prompt laser treatment group.
      Follow-up through 5 years continues.

PMID- 22999635
TI  - Comparison of foveal microstructure imaging with different spectral domain
      optical coherence tomography machines.
AB  - PURPOSE: To investigate the reproducibility of imaging the foveal microstructures
      of healthy eyes with 3 spectral domain optical coherence tomography (SD-OCT)
      machines: Cirrus (Carl Zeiss Meditec Inc.), Spectralis (Heidelberg Engineering),
      and Topcon (Topcon 3D OCT-1000 Mark II). DESIGN: Cross-sectional, prospective,
      noninterventional study. PARTICIPANTS: Images were obtained for 50 eyes of 50
      healthy undilated volunteers without ocular pathology in a clinical setting.
      METHODS: The fovea of all subjects was imaged using Cirrus, Spectralis, and
      Topcon. MAIN OUTCOME MEASURES: Among the 4 hyperreflective bands in the outer
      subfovea on SD-OCT imaging, the innermost band (external limiting membrane [ELM]
      band), the second innermost band (second band), and the third innermost band
      (third band) were classified as "continuous," "disrupted," or "none" by 2
      independent raters. Weighted kappa-coefficient analysis and/or Fisher exact test
      were used to compare interrater, intermachine, and intramachine agreement
      measurements. The sensitivity of each machine was also evaluated. RESULTS: The
      group of 50 subjects consisted of 22 men and 28 women, with an average age of
      31.4 years (range, 21-52 years). Interrater agreement for 3 bands was high (kappa
      = 0.876, 0.738, and 0.774) with Cirrus, Spectralis, and Topcon, respectively. The
      sensitivity of each machine was high for the ELM band (0.92, 0.98, and 0.96), the
      second band (all 1.00), and the third band (0.96, 0.94, and 0.88) with Cirrus,
      Spectralis, and Topcon, respectively. The sensitivity of the third band was
      significantly lower than the second band with Topcon (Fisher exact test, P =
      0.027), but the difference was not significant with the other machines.
      Intermachine agreement was fair to moderate for the third band (kappa = 0.65,
      0.512, and 0.464) and for all bands (kappa = 0.531, 0.369, and 0.362) between
      Cirrus-Spectralis, Spectralis-Topcon, and Topcon-Cirrus, respectively; however,
      it was not significant for ELM band (kappa = -0.027) between Spectralis-Topcon.
      CONCLUSIONS: In healthy adults with normal vision, there was almost perfect
      reproducibility between raters for foveal microstructural images acquired with
      the Cirrus, Spectralis, and Topcon devices. The machines have good sensitivity to
      image foveal microstructures, and the sensitivity does not differ significantly
      among machines; however, they are not necessarily identical or interchangeable
      for imaging certain structures.

PMID- 22999636
TI  - Unilateral herpes zoster ophthalmicus results in bilateral corneal nerve
      alteration: an in vivo confocal microscopy study.
AB  - PURPOSE: Herpes zoster ophthalmicus (HZO), thought to be a unilateral disease,
      results in loss of corneal sensation, leading to neurotrophic keratopathy. This
      study aimed to analyze bilateral corneal nerve changes in patients with HZO by in
      vivo confocal microscopy (IVCM) and their correlation with corneal sensation as a
      measure of nerve function. DESIGN: Prospective, cross-sectional, controlled,
      single-center study. PARTICIPANTS: Twenty-seven eyes with the diagnosis of HZO
      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 corneal nerve density, total nerve number, main nerve
      trunks, branching, and tortuosity were evaluated after IVCM and were correlated
      to corneal sensation, disease duration, and number of recurrences. RESULTS: Eyes
      with herpes zoster ophthalmicus had a significant (P<0.001) decrease in total
      nerve length (595.8+/-358.1 vs. 2258.4+/-989.0 MUm/frame), total number of nerves
      (5.4+/-2.8 vs. 13.1+/-3.8), number of main nerve trunks (2.3+/-1.1 vs. 4.7+/
      1.2), and number of nerve branches (3.2+/-2.3 vs. 8.4+/-3.7) as compared with
      controls. In the contralateral clinically unaffected eyes, total nerve length
      (1053.1+/-441.4 MUm/frame), total number of nerves (8.3+/-2.9), and main nerve
      trunks (3.1+/-1.0) also were decreased significantly as compared with controls
      (P<0.01). Reduced nerve density, total nerve count, main trunks, and tortuosity
      was correlated significantly with corneal sensation across all subgroups
      (P<0.001). CONCLUSIONS: Patients with unilateral HZO demonstrated a profound and
      significant bilateral loss of the corneal nerve plexus as compared with controls,
      demonstrating bilateral changes in a clinically unilateral disease. Loss of
      corneal sensation strongly correlated with subbasal nerve plexus alterations as
      shown by IVCM. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or
      commercial interest in any materials discussed in this article.

PMID- 22999637
TI  - Has Vietnam Health care funds for the poor policy favored the elderly poor?
AB  - BACKGROUND: The elderly population is increasing in Vietnam. Access to health
      services for the elderly is often limited, especially for those in rural areas.
      User fees at public health care facilities and out-of-pocket payments for health
      care services are major barriers to access. With the aim of helping the poor
      access public health care services and reduce health care expenditures (HCE), the
      Health Care Funds for the Poor policy (HCFP) was implemented in 2002. The aim of
      this study is to investigate the impacts of this policy on elderly households.
      METHODS: Elderly households were defined as households which have at least one
      person aged 60 years or older. The impacts of HCFP on elderly household HCE as a
      percentage of total expenditure and health care utilization were assessed by a
      double-difference propensity score matching method using panel data of 3,957
      elderly households in 2001, 2003, 2005 and 2007, of which 509 were classifies as
      "treated" (i.e. covered by the policy). Variables included in a logistic
      regression for estimating the propensity scores to match the treated with the
      control households, were household and household-head characteristics. RESULTS:
      In the first time period (2001-2003) there were no significant differences
      between treated and controls. This can be explained by the delay in implementing
      the policy by the local governments. In the second (2001-2005) and third period
      (2001-2007) the utilizations of Communal Health Stations (CHS) and go-to
      pharmacies were significant. The treated were using CHS and pharmacies more
      between 2001 and 2007 while control households decreased their use. CONCLUSION:
      The main findings suggest HCFP met some goals but not all in the group of
      households having at least one elderly member. Utilization of CHS and pharmacies
      increased while the change in HCE as a proportion of total expenditures was not
      significant. To some extent, private health care and self-treatment are replaced
      by more utilization of CHS, indicating the poor elderly are better off. However,
      further efforts are needed to help them access higher levels of public health
      care (e.g. district health centers and provincial/central hospitals) and to
      reduce their HCE.

PMID- 22999638
TI  - Detection of the cytotoxicity of water-insoluble fraction of cigarette smoke by
      direct exposure to cultured cells at an air-liquid interface.
AB  - For the biological evaluation of cigarette smoke in vitro, the particulate phase
      (PP) and the gas vapor phase (GVP) of mainstream smoke have usually been
      collected individually and exposed to biological material such as cultured cells.
      Using this traditional method, the GVP is collected by bubbling in an aqueous
      solution such as phosphate-buffered saline (PBS). In such a way the water
      insoluble GVP fraction is excluded from the GVP, meaning that the toxic potential
      of the water-insoluble GVP fraction has hardly been investigated so far. In our
      experiments we used a direct exposure method to expose cells at the air-liquid
      interface (ALI) to the water-insoluble GVP fraction for demonstrating its
      toxicological/biological activity. In order to isolate the water-insoluble GVP
      fraction from mainstream smoke, the GVP was passed through 6 impingers connected
      in series with PBS. After direct exposure of Chinese hamster ovary cells (CHO-K1)
      with the water-insoluble GVP fraction in the CULTEX((r)) system its cytotoxicity
      was assayed by using the neutral red uptake assay. The water-insoluble GVP
      fraction was proven to be less cytotoxic than the water-soluble GVP fraction, but
      showed a significant effect in a dose-dependent manner. The results of this study
      showed that the direct exposure of cultivated cells at the air-liquid interface
      offers the possibility to analyze the biological and toxicological activities of
      all fractions of cigarette smoke including the water-insoluble GVP fraction.

PMID- 22999639
TI  - Expression of Egr1 and p53 in human carotid plaques and apoptosis induced by 7
      oxysterol or p53.
AB  - Egr-1 and p53 are involved in pathology of both atherosclerosis and cancer.
      However, it is unknown whether p53 and Egr1 are interactively involved in
      apoptosis in atherosclerosis. We found that in human carotid plaques, the
      expression of p53 was inversely correlated with Egr1. In U937 cells, 7beta
      hydroxycholesterol and 7-ketocholesterol induced production of reactive oxygen
      species (ROS), transient up-regulation of Egr1 followed by late induction of p53
      and apoptosis. Cells with nuclear fragmentation induced by 7-oxysterol or p53
      showed increased levels of p53, but decreased levels of Egr1. In conclusion, ROS
      induced by 7-oxysterols may function as an early initiator of Egr1 expression.
      The late induced p53 by 7-oxysterols contributes to apoptotic cell death and is
      linked to the reduction of Egr1 levels, which resembles the differential
      expression of p53 and Egr1 in human atheroma progression.

PMID- 22999640
TI  - Could the incidence of healthcare infections in Europe simply be a reflection of
      overall quality standards?

PMID- 22999641
TI  - Laboratory exposures to brucella in the UK and Ireland.

PMID- 22999642
TI  - Influence of preparation techniques to the strength of the bone-cement interface
      behind the flange in total knee arthroplasty.
AB  - INTRODUCTION: Recent clinical studies show an increased risk of femoral loosening
      in high-flexion TKA. Loosening seems to occur behind the anterior flange, which
      is covering both cancellous bone and cortical bone. It is important to optimize
      the interface strength between cement and both bone types to increase femoral
      component fixation. This study was performed to determine the cement-cortical
      bone interface strength for different preparation techniques. MATERIAL AND
      METHODS: A pure tensile and shear force was applied to interface specimens. The
      cortical surface area was prepared in three different ways: (1) Unprepared
      cortical bone with periosteum; (2) Periosteum removed and cortical bone roughened
      with a rasp; (3) Periosteum removed and three O 3.2mm holes drilled through the
      cortex. A reference group was added with a cancellous bone surface. RESULTS: The
      interface tensile strength of Group 1 was 0.06 MPa and the shear strength was
      0.05 MPa. For Group 2, respectively 0.22 MPa and 1.12 MPa. For Group 3,
      respectively 1.15 MPa and 1.77 MPa. For cancellous bone a tensile strength of
      1.79 MPa and a shear strength of 3.85 MPa were measured. CONCLUSION: The strength
      of the cement-cancellous bone interface is superior to the cement-cortical bone
      interface. The preferred preparation technique of the cortical bone is to remove
      all the periosteum and drill holes through the cortex within the footprint of the
      anterior flange, to prevent cortical weakening. CLINICAL RELEVANCE: Ultimately,
      the proposed preparation technique will lead to longer implant survival,
      particularly for prostheses which are used in the high-flexion range.

PMID- 22999643
TI  - Serum LDH elevation should not be necessarily attributed to disease activity in
      patients with thrombotic thrombocytopenic purpura.

PMID- 22999644
TI  - One swallow doesn't bring spring. Response to letter to editor.

PMID- 22999645
TI  - Caring for critical care boarders in the emergency department.

PMID- 22999646
TI  - Endovascular treatment of renal aneurysms: a series of 18 cases.
AB  - PURPOSE: To retrospectively analyze the results and complications of the
      endovascular treatment of 18 renal aneurysms. METHODS: From 2002 to 2011, 15
      patients (aged 31-76), with 18 renal aneurysms, were admitted in our institution
      for treatment by embolization. Except one, all were wide-necked aneurysms. One
      aneurysm was treated by occluding the parent artery considering its distal
      location; a small-necked aneurysm was treated by simple coiling, and the
      remaining 16 were embolized utilizing adjunctive techniques to protect the parent
      artery. We analyzed the rates of technical success, complication and clinical
      consequence, post-operative occlusion and recurrence. RESULTS: There was a 100%
      technical success rate. 15 aneurysms showed a total occlusion on the post
      treatment angiogram. 2 aneurysms demonstrated neck remnants, and one had an
      intrasaccular residual in-flow. Two minor post-operative complications were
      encountered but resolved over time. No delayed clinical complications were
      observed and the long-term angiographic follow-up demonstrated stability of the
      occlusion of the target renal aneurysm with no major recurrence. CONCLUSION:
      Complications of the embolization of renal aneurysms are rare. Endovascular
      treatment should therefore be considered at first for the treatment of renal
      aneurysms.

PMID- 22999647
TI  - Computed tomography of the bowel: a prospective comparison study between four
      techniques.
AB  - OBJECTIVES: The major objective was to prospectively compare the grade of bowel
      distension obtained with four different computed tomography (CT) techniques
      dedicated for the examination of the small intestine (CT enteroclysis [CTE] and
      enterography [CTe]), of the colon (CT with water enema [CT-WE]), or both (CTe
      with water enema [CTe-WE]). The secondary objective was to assess patients'
      tolerance toward each CT protocol. MATERIALS AND METHODS: Recruitment was
      designed to obtain four groups of the same number of patients (30). Each group
      corresponded to a specific CT technique, for a total of 120 consecutive
      outpatients (65 male and 55 female, mean age 51.09 +/- 13.36 years). CTE was
      performed after injection of methylcellulose through a nasojejunal tube, while in
      the CTe protocol a polyethylene glycol electrolyte solution was orally
      administered to patients prior to the CT acquisition. In the CT-WE protocol
      intraluminal contrast (water) was administered only by a rectal enema, while CTe
      WE technique included both a rectal water enema and oral ingestion of neutral
      contrast material to obtain a simultaneous distension of small and large bowel.
      CT studies were reviewed in consensus by two gastrointestinal radiologists who
      performed a quantitative and qualitative analysis of bowel distension on a per
      segment basis. The presence and type of adverse effects were recorded. RESULTS:
      CTE provided the best distension of jejunal loops (median diameter 27 mm, range
      17-32 mm) when compared to all the other techniques (p<0.0001). The frequency of
      patients with an adequate distension of the terminal ileum was not significantly
      different among the four groups (p=0.0608). At both quantitative and qualitative
      analysis CT-WE and CTe-WE determined a greater and more consistent luminal
      filling of the large intestine than that provided by both CTE and CTe (p<0.0001
      for all colonic segments). Adverse effects were more frequent in patients
      belonging to the CTE group (p<0.0028). CONCLUSIONS: CTE allows an optimal
      distension of jejunal loops, but it is the most uncomfortable CT protocol. When
      performing CT-WE, an adequate retrograde distension of the terminal ileum was
      provided in a particularly high percentage of patients. CTe-WE provides a
      simultaneous optimal distension of both small and large bowel.

PMID- 22999648
TI  - Hyperpolarized (3)He magnetic resonance imaging: comparison with four-dimensional
      x-ray computed tomography imaging in lung cancer.
AB  - RATIONALE AND OBJECTIVES: Pulmonary functional imaging using four-dimensional x
      ray computed tomographic (4DCT) imaging and hyperpolarized (3)He magnetic
      resonance imaging (MRI) provides regional lung function estimates in patients
      with lung cancer in whom pulmonary function measurements are typically dominated
      by tumor burden. The aim of this study was to evaluate the quantitative spatial
      relationship between 4DCT and hyperpolarized (3)He MRI ventilation maps.
      MATERIALS AND METHODS: Eleven patients with lung cancer provided written informed
      consent to 4DCT imaging and MRI performed within 11 +/- 14 days. Hyperpolarized
      (3)He MRI was acquired in breath-hold after inhalation from functional residual
      capacity of 1 L hyperpolarized (3)He, whereas 4DCT imaging was acquired over a
      single tidal breath of room air. For hyperpolarized (3)He MRI, the percentage
      ventilated volume was generated using semiautomated segmentation; for 4DCT
      imaging, pulmonary function maps were generated using the correspondence between
      identical tissue elements at inspiratory and expiratory phases to generate
      percentage ventilated volume. RESULTS: After accounting for differences in image
      acquisition lung volumes ((3)He MRI: 1.9 +/- 0.5 L ipsilateral, 2.3 +/- 0.7 L
      contralateral; 4DCT imaging: 1.2 +/- 0.3 L ipsilateral, 1.3 +/- 0.4 L
      contralateral), there was no significant difference in percentage ventilated
      volume between hyperpolarized (3)He MRI (72 +/- 11% ipsilateral, 79 +/- 12%
      contralateral) and 4DCT imaging (74 +/- 3% ipsilateral, 75 +/- 4% contralateral).
      Spatial correspondence between 4DCT and (3)He MRI ventilation was evaluated using
      the Dice similarity coefficient index (ipsilateral, 86 +/- 12%; contralateral, 88
      +/- 12%). CONCLUSIONS: Despite rather large differences in image acquisition
      breathing maneuvers, good spatial and significant quantitative agreement was
      observed for ventilation maps on hyperpolarized (3)He MRI and 4DCT imaging,
      suggesting that pulmonary regions with good lung function are similar between
      modalities in this small group of patients with lung cancer.

PMID- 22999649
TI  - [Isolated intracranial hypertension as the presenting sign of Lyme disease].
AB  - We report the case of an eight-year-old patient referred by his primary care
      physician for chronic headache. Bilateral papilledema was observed along with
      right sixth cranial nerve palsy, leading to the diagnosis of intracranial
      hypertension. Head CT showed no mass lesion. Lyme serology was positive by both
      Elisa and Western blot. Anti-Borrelia antibodies were positive in the
      cerebrospinal fluid, with intrathecal synthesis confirming neuroborreliosis.
      Clinical response to ceftriaxone and acetazolamide was favorable. Intracranial
      hypertension is rarely caused by Lyme disease. Ophthalmologists should be aware
      of this clinical presentation, since the presenting clinical signs may be purely
      ophthalmologic. In addition, early diagnosis may avoid optic nerve atrophy or
      disease spread.

PMID- 22999650
TI  - [Unilateral optic disc edema: retrospective study of fifty-two patients].
AB  - PURPOSE: To study the epidemiologic and clinical characteristics of patients with
      unilateral optic disc edema diagnosed in the emergency room (ER). PATIENTS AND
      METHODS: Retrospective observational study of all cases of unilateral optic disc
      edema seen in the ophthalmology ER of Bordeaux University Hospital, France,
      between October 1, 2008 and October 31, 2009. RESULTS: Fifty-two patients with
      unilateral optic disc edema were studied, including 61.5% women (n=32) and 38.5%
      men (n=20). Mean age was 53.5 years (+/- 22.9). Male patients were older than
      female (61.1 years vs 48.7 years, P=0.05). Final diagnosis was anterior ischemic
      optic neuropathy (27 cases), papillitis (17 cases), papilledema (three cases),
      and pseudoedema (two cases). No etiologies were identified for the remaining
      three patients. CONCLUSION: Our study discusses the diagnostic approach for
      patients presenting with unilateral optic disc edema; this discussion may help to
      improve clinical practice.

PMID- 22999651
TI  - [Pediatric ophthalmologic and orthoptic evaluation of the dyspraxic child].
AB  - Orthoptic and ophthalmologic consultation is an essential step in the diagnosis
      and treatment of learning disorders, particularly in children with dyspraxia.
      Such a specialized consultation allows identification of cognitive visual
      disorders, especially oculomotor or visual-spatial impairment, which disrupt the
      cognitive processes involved in key academic tasks such as reading or
      handwriting. It is therefore essential to screen and manage these disorders early
      in order to implement a rehabilitation plan and counsel educators so as to
      facilitate learning. After describing cognitive visual disorders in the context
      of dyspraxia, we discuss principal signs, assessment and ophthalmologic and
      orthoptic management as conducted in our practice. Several clinical cases
      illustrate our approach.

PMID- 22999652
TI  - Altering the way the optic nerve head responds to intraocular pressure-a
      potential approach to glaucoma therapy.
AB  - Over the past decade, engineering principles have been used to explain why a
      mechanical load, intraocular pressure, can lead to the development of
      glaucomatous optic neuropathy. This has led to the 'biomechanical theory' of
      glaucoma, which posits that the behavior of optic nerve head connective tissues
      (specifically within the peripapillary sclera and lamina cribrosa) in response to
      intraocular pressure (regardless of its magnitude) can directly and indirectly
      influence the physiology and pathophysiology of the optic nerve head. Given that
      the biomechanics of the sclera and lamina cribrosa probably influence retinal
      ganglion cell loss in glaucoma, the idea that altering biomechanical behavior
      might be protective against glaucoma is an appealing notion. There is some
      evidence to suggest that stiffening the peripapillary sclera may be protective
      against the development of glaucoma in an animal model. It is technically
      possible to stiffen the sclera in vivo using collagen cross-linking techniques
      already applied in vivo to the cornea in the treatment of keratoconus. It has yet
      to be established whether scleral cross-linking is safe in humans and that it
      confers anything more than a theoretical advantage in terms of reducing the risk
      of glaucomatous damage.

PMID- 22999653
TI  - Maintenance of retinal ganglion cell mitochondrial functions as a neuroprotective
      strategy in glaucoma.
AB  - Loss of vision in glaucoma occurs because retinal ganglion cells (RGCs) die. RGCs
      have probably more mitochondria than any other neurone in the CNS. It is proposed
      that stress to mitochondria of individual RGCs is a major trigger of the disease
      and also provides an explanation why different RGCs die at different times.
      Pharmacological agents that can maintain mitochondrial functions, in particular
      to attenuate oxidative stress and to sustain energy production, might therefore
      provide a novel way of slowing down RGC death and help in the treatment of
      glaucoma.

PMID- 22999654
TI  - Testosterone administration in women increases amygdala responses to fearful and
      happy faces.
AB  - Data from both rodents and humans show that testosterone reduces fear. This
      effect is hypothesized to result from testosterone's down regulating effects on
      the amygdala, a key region in the detection of threat and instigator of fight-or
      flight behavior. However, neuroimaging studies employing testosterone
      administration in humans have consistently shown increased amygdala responsivity.
      Yet, no study to date has investigated specifically how testosterone affects the
      amygdala response to fearful emotional expressions. Such stimuli signal the
      presence of environmental threat and elicit robust amygdala responses that have
      consistently been associated with anxious traits. In the present study, we
      therefore used functional magnetic resonance imaging combined with a single
      administration of 0.5mg testosterone in 12 healthy women to assess testosterone's
      effects on amygdala responses to dynamic fearful (and happy control) faces. Our
      results show that both stimuli activate the amygdala. Notably, testosterone
      increased the amygdala response to both stimuli, and to an equal degree. Thus,
      testosterone appears not to reduce fear by attenuating the amygdala response
      toward signals of threat. Data further show that testosterone selectively
      increases activation of the superficial amygdala (SFA) and, to a lesser extent,
      the basolateral amygdala (BLA). No effect was found in the central nucleus, which
      is involved in the generation of autonomic fear responses. Both the SFA and BLA
      are considered input regions, and enhanced activation by testosterone might
      reflect the role of this hormone in adaptive responding to socially relevant
      stimuli. Furthermore, literature on the distinct roles of the SFA and BLA in fear
      processing show that increased activation of these subregions of the amygdala is
      consistent with a fear reducing effect of testosterone.

PMID- 22999656
TI  - pH-dependent mechanisms of methylene blue reacting with tunneled manganese oxide
      pyrolusite.
AB  - This study examined the reaction of methylene blue (MB) with tunneled manganese
      oxide pyrolusite regarding pH and reaction time. MB was cleaved through N
      demethylation, in which reaction azure B (AB), azure A (AA), azure C (AC), and
      thionin (TH) were stepwise generated at all tested pH. Pyrolusite predominantly
      serves as the oxidant in the oxidative degradation of MB at a pH under the pHiep
      of pyrolusite (4.70) while playing the role of the catalyst at pH higher than
      pHiep. Among all oxidative products and original MB molecule, TH is the alone
      compound adsorbed onto the pyrolusite surface at all tested pH. However, the
      quantity of adsorbed TH increases with pH because of the stronger affinity
      between the cationic TH molecule and the more negatively charged surface of
      pyrolusite with pH increasing. Because the lattice oxygen and surface hydroxyl
      groups form excited oxygen firstly to cause the oxidation of MB, the tunneled
      pyrolusite with less constrained corner and edge oxygen catalytically promote the
      oxidation reaction at pH beyond pHiep. The vacancy of the consumed lattice oxygen
      forms the active sites for the other oxidation and could be replenished by
      molecular oxygen to complete a catalytic cycle.

PMID- 22999655
TI  - Dynamic changes in brain aromatase activity following sexual interactions in
      males: where, when and why?
AB  - It is increasingly recognized that estrogens produce rapid and transient effects
      at many neural sites ultimately impacting physiological and behavioral endpoints.
      The ability of estrogens to acutely regulate cellular processes implies that
      their concentration should also be rapidly fine-tuned. Accordingly, rapid changes
      in the catalytic activity of aromatase, the limiting enzyme for estrogen
      synthesis, have been identified that could serve as a regulatory mechanism of
      local estrogen concentrations. However, the precise anatomical localization, time
      course, triggering stimuli and functional significance of these enzymatic changes
      in vivo are not well understood. To address these issues as to where, when and
      why aromatase activity (AA) rapidly changes after sexual interactions, AA was
      assayed in six populations of aromatase-expressing cells microdissected from the
      brain of male quail that experienced varying durations of visual exposure to or
      copulation with a female. Sexual interactions resulted in a rapid AA inhibition.
      This inhibition occurred in specific brain regions (including the medial preoptic
      nucleus), in a context-dependent fashion and time-scale suggestive of post
      translational modifications of the enzyme. Interestingly, the enzymatic
      fluctuations occurring in the preoptic area followed rather than preceded
      copulation and were tied specifically to the female's presence. This pattern of
      enzymatic changes suggests that rapid estrogen effects are important during the
      motivational phase of the behavior to trigger physiological events essential to
      activate mate search and copulation.

PMID- 22999657
TI  - Performance of pilot-scale constructed wetlands for secondary treatment of
      chromium-bearing tannery wastewaters.
AB  - Tannery operations consist of converting raw animal skins into leather through a
      series of complex water- and chemically-intensive batch processes. Even when
      conventional primary treatment is supplemented with chemicals, the wastewater
      requires some form of biological treatment to enable the safe disposal to the
      natural environment. Thus, there is a need for the adoption of low cost,
      reliable, and easy-to-operate alternative secondary treatment processes. This
      paper reports the findings of two pilot-scale wetlands for the secondary
      treatment of primary effluents from a full tannery operation in terms of
      resilience (i.e., ability to produce consistent effluent quality in spite of
      variable influent loads) and reliability (i.e., ability to cope with sporadic
      shock loads) when treating this hazardous effluent. Areal mass removal rates of
      77.1 g COD/m2/d, 11 g TSS/m2/d, and 53 mg Cr/m2/d were achieved with a simple
      gravity-flow horizontal subsurface flow unit operating at hydraulic loading rates
      of as much as 10 cm/d. Based on the findings, a full-scale wetland was sized to
      treat all the effluent from the tannery requiring 68% more land than would have
      been assumed based on literature values. Constructed wetlands can offer treatment
      plant resilience for minimum operational input and reliable effluent quality when
      biologically treating primary effluents from tannery operations.

PMID- 22999659
TI  - Acceptable self-promotion.

PMID- 22999658
TI  - The burden of disease from pediatric lead exposure at hazardous waste sites in 7
      Asian countries.
AB  - Identification and systematic assessment of hazardous wastes sites in low and
      middle-income countries has lagged. Hazardous waste problems are especially
      severe in lower income Asian countries where environmental regulations are non
      existent, nonspecific or poorly enforced. In these countries extensive
      unregulated industrial development has created waste sites in densely populated
      urban areas. These sites appear to pose significant risks to public health, and
      especially to the health of children. To assess potential health risks from
      chemical contamination at hazardous waste sites in Asia, we assessed 679 sites. A
      total of 169 sites in 7 countries were classified as contaminated by lead. Eighty
      two of these sites contained lead at levels high enough to produce elevated blood
      lead levels in surrounding populations. To estimate the burden of pediatric lead
      poisoning associated with exposure to lead in soil and water at these 82 lead
      contaminated sites, we used standard toxicokinetic models that relate levels of
      lead in soil and water to blood lead levels in children. We calculated blood lead
      levels, and we quantified losses of intelligence (reductions in IQ scores) that
      were attributable to lead exposure at these sites. We found that 189,725 children
      in the 7 countries are at risk of diminished intelligence as a consequence of
      exposure to elevated levels of lead in water and soil at hazardous waste sites.
      Depending on choice of model, these decrements ranged from 4.94 to 14.96 IQ
      points. Given the restricted scope of this survey and the conservative estimation
      procedures employed, this number is almost certainly an underestimate of the full
      burden of disease. Exposure to toxic chemicals from hazardous waste sites is an
      important and heretofore insufficiently examined contributor to the Global Burden
      of Disease.

PMID- 22999660
TI  - Early prediction of maxillary canine impaction from panoramic radiographs.

PMID- 22999662
TI  - The buck stops here.

PMID- 22999664
TI  - Treating obstructive sleep apnea: the case for oral appliances.

PMID- 22999665
TI  - Treating obstructive sleep apnea: the case for surgery.

PMID- 22999666
TI  - Dental crowding as a caries risk factor: a systematic review.
AB  - INTRODUCTION: The association between dental crowding and dental caries has long
      been accepted because of increased food accumulation and plaque retention in
      areas of crowding. The aim of this review was to evaluate this potential causal
      relationship systematically. METHODS: Six electronic databases were accessed,
      supplemented by manual searching of the references of the relevant retrieved
      articles, peer-reviewed orthodontic journals, and gray literature. Search terms
      included caries, decay, crowding, and irregularity. Non-English articles were
      excluded from the review in the study-selection stage. Data extraction and
      evaluation of primary studies were performed independently by 2 reviewers.
      RESULTS: The initial search retrieved 6914 citations. However, only 18 articles
      met the inclusion criteria. The qualitative systematic review included 8 studies,
      with articles of low or moderate quality. No association between crowding and
      caries was reported in 4 studies, a significant negative correlation was found in
      2 studies, 1 study showed a direct and significant relationship, and another
      study showed a positive association in the mandibular anterior region but an
      inverse correlation in the maxillary posterior region. CONCLUSIONS: To date,
      there are no high-quality studies to resolve the possible association between
      dental crowding and caries; further high-quality longitudinal studies are needed
      to clarify this relationship.

PMID- 22999667
TI  - Reporting quality of abstracts of randomized controlled trials published in
      leading orthodontic journals from 2006 to 2011.
AB  - INTRODUCTION: Optimal reporting of randomized trials and abstracts enhances
      transparency and facilitates assessment and identification of trials. The purpose
      of this study was to investigate the quality of reporting of abstracts of
      randomized controlled trials published in orthodontic journals. METHODS:
      Electronic searches with supplementary hand searching to identify randomized
      controlled trials in the American Journal of Orthodontics and Dentofacial
      Orthopedics, the Angle Orthodontist, the European Journal of Orthodontics, and
      the Journal of Orthodontics from 2006 to 2011 were undertaken. The completeness
      of abstract reporting was evaluated with a modified CONSORT for abstracts
      statement checklist. The data were analyzed by using descriptive statistics
      followed by univariate and multivariate examinations of statistical associations
      (P = 0.05). RESULTS: Abstracts of 117 randomized controlled trials were
      identified and assessed. Most were published in either the American Journal of
      Orthodontics and Dentofacial Orthopedics (53%) or the Angle Orthodontist (23%);
      most abstracts (85.5%) were structured. The mean overall reporting quality score
      was 60.2%. In relation to individual quality items, most abstracts demonstrated
      clear reporting of interventions (97.4%), objectives (93.2%), and number of
      participants randomized (95.7%). Insufficient reporting of randomization
      procedures, allocation concealment, blinding, and failure to report confidence
      intervals and harms were almost universal. Registrations of randomized controlled
      trials and sources of funding were not reported in any of the identified
      abstracts. The highest reporting score was noted in the Journal of Orthodontics
      (66%; 95% confidence interval, 63.5-68.7). CONCLUSIONS: The quality of reporting
      of abstracts of randomized controlled trials in orthodontic journals is
      suboptimal. In view of the primacy of research abstracts, efforts should be made
      to improve their reporting.

PMID- 22999668
TI  - Effects of buccal corridors on smile esthetics in Japanese and Korean
      orthodontists and orthodontic patients.
AB  - INTRODUCTION: The purpose of this study was to evaluate the influence of the size
      of buccal corridors on the assessment of attractive smile esthetics by Japanese
      and Korean orthodontists and orthodontic patients. METHODS: Buccal corridors were
      modified digitally from 0% to 25% compared with the inner intercommissural width.
      Using a visual analog scale, 41 Japanese and 25 Korean orthodontists, and 96
      Japanese and 72 Korean orthodontic patients (15-29 years old) rated the
      attractiveness of 6 smiles with altered buccal corridors. The influence of the
      size of the buccal corridor on smile esthetics was assessed. RESULTS: Although
      there was no significant sex difference in judging the effects of buccal
      corridors for the Korean and Japanese orthodontists, significant sex differences
      were shown for the Japanese orthodontic patients. There were significant
      differences in the 6 levels of median esthetic scores for all groups: 0%, 5%, and
      10% buccal corridors in the smiles tended to be preferred to the other smiles, to
      become clinically significant for all groups. The median esthetic score decreased
      to become clinically significant from 10% to 15% buccal corridors for all groups.
      CONCLUSIONS: Japanese and Korean orthodontists and orthodontic patients prefer
      narrow or medium buccal corridors to broad buccal corridors.

PMID- 22999669
TI  - Bone stress when miniplates are used for orthodontic anchorage: finite element
      analysis.
AB  - INTRODUCTION: The success rate of miniplates is superior to that of other
      temporary anchorage devices; nevertheless, the biomechanical behavior of
      miniplates during orthodontic use is not totally understood. The aim of this
      study was to investigate bone stress by finite element analysis when miniplates
      are used for orthodontic anchorage. METHODS: A 3-dimensional model consisting of
      a bone block integrated with a miniplate and fixation screw system was
      constructed to simulate various types of miniplates, screw numbers, screw
      lengths, cortex thicknesses, and force magnitudes and directions. RESULTS: The
      peak von Mises cortex stress values were highest with the I-type plates followed
      by the L-type, Y-type, and T-type plates. Bone stress decreased as the screw
      numbers increased but was not related to screw length. Bone stress increased as
      the cortex thickness decreased. Bone stress was linearly proportional to the
      force magnitude, and the highest values were produced when the force was in the
      forward direction. CONCLUSIONS: When a T- or Y-type plate is used, or when the
      force direction is in the tensile mode, bone stress decreases. Bone stress also
      decreases as the screw numbers increase and as the cortex thickness increases.
      Furthermore, it decreases as the force magnitude becomes less.

PMID- 22999670
TI  - Deep overbite malocclusion: analysis of the underlying components.
AB  - INTRODUCTION: A deepbite malocclusion should not be approached as a disease
      entity; instead, it should be viewed as a clinical manifestation of underlying
      discrepancies. The aim of this study was to investigate the various skeletal and
      dental components of deep bite malocclusion, the significance of the contribution
      of each, and whether there are certain correlations between them. METHODS: Dental
      and skeletal measurements were made on lateral cephalometric radiographs and
      study models of 124 patients with deepbite. These measurements were statistically
      analyzed. RESULTS: An exaggerated curve of Spee was the greatest shared dental
      component (78%), significantly higher than any other component (P = 0.0335). A
      decreased gonial angle was the greatest shared skeletal component (37.1%), highly
      significant compared with the other components (P = 0.0019). A strong positive
      correlation was found between the ramus/Frankfort horizontal angle and the gonial
      angle; weaker correlations were found between various components. CONCLUSIONS: An
      exaggerated curve of Spee and a decreased gonial angle were the greatest
      contributing components. This analysis of deepbite components could help
      clinicians design individualized mechanotherapies based on the underlying cause,
      rather than being biased toward predetermined mechanics when treating patients
      with a deepbite malocclusion.

PMID- 22999671
TI  - Molecular detection of Aggregatibacter actinomycetemcomitans on metallic brackets
      by the checkerboard DNA-DNA hybridization technique.
AB  - INTRODUCTION: The purpose of this randomized clinical study was to evaluate the
      presence of the periodontal pathogen Aggregatibacter actinomycetemcomitans on
      metallic brackets and the effectiveness of a 0.12% chlorhexidine digluconate
      mouthwash in inhibiting this microorganism. METHODS: The study involved 35
      patients of both sexes having orthodontic treatment with fixed appliances between
      the ages of 14 and 22 years, randomized into 2 groups: experimental (n = 17) and
      control (n = 18). Two new metallic brackets were placed on the patients'
      premolars, and the subjects rinsed with a solution of 0.12% chlorhexidine
      digluconate or a placebo solution twice a week for 30 days. After that, the
      brackets were removed and underwent microbiologic analysis with the checkerboard
      DNA-DNA hybridization technique. Data were analyzed by using the Student t,
      Fisher exact, and Mann-Whitney tests at the significance level of 5%. RESULTS:
      The results showed that A actinomycetemcomitans was present in all brackets from
      the subjects in the control group vs 83% of the subjects who rinsed with
      chlorhexidine digluconate (P <0.0001). There were also significantly lower levels
      of this species in the chlorhexidine digluconate group compared with the control
      group (P = 0.0003). CONCLUSIONS: We concluded that 0.12% chlorhexidine
      digluconate rinsing, twice a week for 30 days during orthodontic treatment, is
      effective in reducing the presence and levels of A actinomycetemcomitans on
      metallic brackets.

PMID- 22999672
TI  - Treatment effects of bonded spurs associated with high-pull chincup therapy in
      the treatment of patients with anterior open bite.
AB  - INTRODUCTION: The aim of this prospective clinical study was to investigate the
      cephalometric changes produced by bonded spurs associated with high-pull chincup
      therapy in children with Angle Class I malocclusion and anterior open bite.
      METHODS: Thirty patients with an initial mean age of 8.14 years and a mean
      anterior open bite of -3.93 mm were treated with bonded spurs associated with
      chincup therapy for 12 months. An untreated control group of 30 subjects with an
      initial mean age of 8.36 years and a mean anterior open bite of -3.93 mm and the
      same malocclusion was followed for 12 months for comparison. Student t tests were
      used for intergroup comparisons. RESULTS: The treated group demonstrated a
      significantly greater decrease of the gonial angle, and increase in overbite,
      palatal tipping of the maxillary incisors, and vertical dentoalveolar development
      of the maxillary and mandibular incisors compared with the control group.
      CONCLUSIONS: The association of bonded spurs with high-pull chincup therapy was
      efficient for the correction of the open bite in 86.7% of the patients, with a
      5.23-mm (SD, +/-1.69) overbite increase.

PMID- 22999673
TI  - Kinetics of interleukin-6 and chemokine ligands 2 and 3 expression of periodontal
      tissues during orthodontic tooth movement.
AB  - INTRODUCTION: Mechanical loading induces remodeling of the periodontal ligament
      and the alveolar bone and is mediated by cytokines and chemokines. In this study,
      we investigated the kinetics of interleukin-6 and chemokine ligands 2 and 3
      levels in periodontal ligaments subjected to orthodontic forces. METHODS: We used
      64 premolars in this split-mouth design study. The experimental group consisted
      of premolars subjected to a force of 0.980 N in the apical direction for 3 hours,
      15 hours, 3 days, 12 days, or 21 days with a 0.017 * 0.025-in beta-titanium alloy
      cantilever. The contralateral teeth, without orthodontic appliances, were used as
      controls. The premolars were extracted for orthodontic reasons, and the
      periodontal ligaments were scraped for analysis of cytokine levels by ELISA.
      RESULTS: Compared with the control group, an increase in chemokine ligand 2 was
      observed on days 3 and 12, and increases in interleukin-6 and chemokine ligand 3
      were observed on day 12 in the experimental group. CONCLUSIONS: Our data
      demonstrated differential expressions of interleukin-6 and chemokine ligands 2
      and 3 in periodontal ligaments after mechanical loading; this might reflect the
      distinct roles of these molecules in the bone remodeling process.

PMID- 22999674
TI  - Finite element analysis of the effect of force directions on tooth movement in
      extraction space closure with miniscrew sliding mechanics.
AB  - INTRODUCTION: Miniscrews placed in bone have been used as orthodontic anchorage
      in extraction space closure with sliding mechanics. The movement patterns of the
      teeth depend on the force directions. To move the teeth in a desired pattern, the
      appropriate direction of force must be selected. The purpose of this article is
      to clarify the relationship between force directions and movement patterns.
      METHODS: By using the finite element method, orthodontic movements were simulated
      based on the remodeling law of the alveolar bone. The power arm length and the
      miniscrew position were varied to change the force directions. RESULTS: When the
      power arm was lengthened, rotation of the entire maxillary dentition decreased.
      The posterior teeth were effective for preventing rotation of the anterior teeth
      through an archwire. In cases of a high position of a miniscrew, bodily tooth
      movement was almost achieved. The vertical component of the force produced
      intrusion or extrusion of the entire dentition. CONCLUSIONS: Within the limits of
      the method, the mechanical simulations demonstrated the effect of force direction
      on movement patterns.

PMID- 22999675
TI  - Severe facial asymmetry and unilateral lingual crossbite treated with
      orthodontics and 2-jaw surgery: 5-year follow-up.
AB  - A 33-year-old woman with severe facial asymmetry and unilateral lingual crossbite
      was treated with orthodontics combined with differential maxillary impaction and
      intraoral vertical ramus osteotomy. After 12 months of preoperative orthodontic
      treatment, 2-jaw surgery was performed. The total active treatment time was 18
      months. Both her occlusion and facial appearance were significantly improved by
      the surgical-orthodontic treatment. The occlusion was stable after 5 years of
      retention. Posttreatment records after 5 years showed excellent results with good
      occlusion and long-term stability.

PMID- 22999676
TI  - Orthodontic correction of a transposed maxillary canine and first premolar in the
      permanent dentition.
AB  - The patient was a 16-year-old Japanese girl whose chief complaints were crowding
      and transposition of the maxillary canine and first premolar. A setup model was
      used to preoperatively align the teeth in their transposed positions. The amount
      of postoperative reshaping was estimated for the occlusal surfaces of the teeth.
      However, the patient did not wish to have her teeth reduced by reshaping or to
      have composite materials for restorative camouflage. Because she strongly
      expected alignment of her teeth in the correct intra-arch position, her
      transposed teeth were corrected without extraction of the transposed teeth. Cone
      beam computed tomography was used to obtain more detailed information about the
      transposition, and the direction of tooth movement was examined. Although the
      duration of the treatment was long, both the crowns and the roots of the
      transposed teeth were aligned correctly.

PMID- 22999677
TI  - Functional improvements after orthodontic-surgical reconstruction in a patient
      with multiple maxillofacial fractures.
AB  - Patients with multiple craniofacial fractures often suffer from stomatognathic
      problems after their primary treatment, because administering emergency care is
      the clinician's highest priority. Therefore, optimal bone repositioning is
      sometimes difficult because bone fixation is delayed. Moreover, neither an
      adequate radiographic examination nor an evaluation of primary occlusion is
      available during the repair of fractured bones. The lack of these assessments can
      also lead to occlusal dysfunction after bone fixation. As a result, patients with
      craniofacial fractures often require occlusal reconstruction. This report
      describes the successful occlusal reconstruction with orthodontic-surgical
      treatment of a patient with multiple maxillofacial bone fractures. Combined
      surgery, including an intraoral vertical ramus osteotomy and a mandibular body
      osteotomy, was performed to reposition the deviated mandible after 3 months of
      preoperative orthodontic treatment. The total active treatment period was 25
      months. After treatment, both the facial asymmetry and the anterior open bite
      caused by the skeletal disharmony were significantly improved. Additionally, the
      range of condylar motion, maximum occlusal force, and occlusal contact area
      during maximum clenching were also increased. These stomatognathic functions were
      further enhanced by 2 years of retention. Orthodontic-surgical reconstruction
      appears to improve both facial esthetics and occlusal function in patients with
      facial asymmetry caused by severe traumatic maxillofacial fractures.

PMID- 22999678
TI  - Esthetic periodontal surgery for impacted dilacerated maxillary central incisors.
AB  - Clinicians do not frequently see impacted dilacerated maxillary incisors in their
      patients. When they do, there are several diagnostic and management challenges
      for correcting root dilacerations. An unfavorable esthetic outcome might occur as
      a result of soft-tissue complications during surgical eruption procedures. We
      present 2 patients with an impacted and dilacerated maxillary central incisor.
      Computed tomography scans with 3-dimensional reformation were used to accurately
      assess the positions of the dilacerated teeth, the degree of dilaceration, and
      the stage of root formation. The therapy primarily involved 2-stage crown
      exposure surgery combined with orthodontic traction. An apicoectomy was performed
      on 1 dilacerated tooth; the other exhibited pulp vitality. This article
      highlights the periodontal surgical strategies for the esthetic management of
      inverted crowns. Through periodontal plastic surgery and interdisciplinary
      cooperation, the impacted dilacerated central incisors were properly aligned, and
      successful esthetic results were achieved.

PMID- 22999679
TI  - Three-dimensional ultrashort echo magnetic resonance imaging of orthodontic
      appliances in the natural dentition.
AB  - INTRODUCTION: The purpose of this study was to determine whether ultrashort echo
      time magnetic resonance imaging technology could be used to image teeth with
      orthodontic appliances in place. METHODS: High-resolution 3-T ultrashort echo
      time magnetic resonance imaging was performed on 60 extracted premolars with
      fixed ceramic orthodontic appliances (Clarity, 3M Unitek, Monrovia, Calif;
      Radiance, American Orthodontics, Sheboygan, Wis; and Ice, Ormco, Glendora,
      Calif). The teeth were collected from the orthodontic clinic at the University of
      Alabama at Birmingham, and the institutional review board of the University of
      Alabama at Birmingham approved the study. Linear measurements of tooth morphology
      and orthodontic bracket dimensions were acquired with calipers and compared with
      virtual digital magnetic resonance imaging. The spin echo and high spatial
      resolution multi-slice turbo spin echo were only used for visual comparison with
      the ultrashort echo time slices. Both the caliper and the ultrashort echo time
      magnetic resonance imaging measurements were highly reliable and accurate.
      Comparisons between the 2 methods showed no statistically significant differences
      in any bracket or tooth dimensions, with a P value of >0.05. In general, the
      differences in the values ranged from -0.01 to 0.06 mm. A visual evaluation scale
      was used to assess the quality of the ultrashort echo time magnetic resonance
      images when assessing the delineation of dental hard tissues. RESULTS: The visual
      evaluation scale of the images showed that enamel, dentin, pulp, and ceramic
      orthodontic appliances could be subjectively delineated at a high level with the
      ultrashort echo time magnetic resonance imaging. CONCLUSIONS: The following
      conclusions can be drawn from this prospective study. Ceramic orthodontic
      appliances, without metal components, cause no dental image distortions and are
      readily visible on the ultrashort echo time magnetic resonance imaging scans. The
      measurements comparing linear tooth measurements with virtual digital magnetic
      resonance images demonstrated that magnetic resonance imaging has statistically
      and clinically significant accuracy on external tooth and bracket measurements.
      Visual evaluation of the images showed that enamel, dentin, pulp, and ceramic
      orthodontic appliances could be subjectively delineated at a high level with
      ultrashort echo time magnetic resonance imaging. Metallic slots in ceramic
      appliances cause severe image distortions. These distortions are localized and
      should not affect surrounding tissues in full-volume magnetic resonance imaging.

PMID- 22999680
TI  - Litigation and legislation. Paying the piper.

PMID- 22999681
TI  - Sample calculations for comparing rates.

PMID- 22999684
TI  - Editorial comment.

PMID- 22999685
TI  - Editorial comment.

PMID- 22999682
TI  - Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic
      contact dermatitis and reduces epidermal Langerhans cells in mice.
AB  - BACKGROUND: Histone deacetylases (HDACs) influence chromatin organization,
      representing a key epigenetic regulatory mechanism in cells. Trichostatin A
      (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects.
      Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in
      skin and is regulated by epidermal Langerhans cells (LCs). OBJECTIVE: The aim of
      this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene
      (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells
      during ACD development. METHODS: ACD was induced by sensitizing and challenging
      with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO
      as a control every other day before and during induction of ACD. The ear swelling
      response was measured and skin biopsies from sensitized skin areas were obtained
      for histology. Epidermal cells, thymus, spleen and skin draining lymph nodes were
      collected for immune staining. RESULTS: TSA treatment ameliorated skin lesion
      severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as
      well as LC maturation were significantly reduced in TSA-treated mice. However,
      TSA treatment did not significantly affect the homeostasis of conventional CD4(+)
      and CD8(+) T cells, Foxp3(+)CD4(+) regulatory T cells, iNKT cells, and gammadelta
      T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there
      were no significant differences in IL-4 and IFN-gamma-producing T cells and iNKT
      cells between TSA- and DMSO-treated mice. CONCLUSION: Our findings suggest that
      TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could
      serve as potential therapeutic targets for ACD and other LCs-related skin
      diseases.

PMID- 22999686
TI  - Effect of indomethacin on desmopressin resistant nocturnal polyuria and nocturnal
      enuresis.
AB  - PURPOSE: We evaluated the acute effect of indomethacin on renal water and solute
      handling in children with coexisting monosymptomatic nocturnal enuresis and
      desmopressin resistant nocturnal polyuria, and in healthy controls. MATERIALS AND
      METHODS: A total of 23 subjects were recruited, consisting of 12 children with
      monosymptomatic nocturnal enuresis and nocturnal polyuria with partial or no
      response to desmopressin, and 11 age matched controls. Children completed a 48
      hour inpatient study protocol consisting of fractional urine collections and
      blood samples. Sodium and water intake were standardized. During the second night
      a dose of 50 mg indomethacin was administered orally before bedtime. Diuresis,
      urine osmolalities, clearances and fractional excretions were calculated for
      sodium, potassium, urea, osmoles and solute-free water. Renin, angiotensin II,
      aldosterone and atrial natriuretic peptide were measured in plasma. Prostaglandin
      E(2) was measured in urine. RESULTS: Indomethacin markedly decreased the
      nocturnal sodium, urea and osmotic excretion in children with enuresis and
      controls. The overall effect on nocturnal urine output was inconsistent in the
      group with enuresis. Subjects in whom nocturnal diuresis was decreased following
      administration of indomethacin remained dry. CONCLUSIONS: Prostaglandin
      inhibition leads to antidiuresis, reducing the amount of sodium, urea and osmotic
      excretion in children with monosymptomatic nocturnal enuresis and desmopressin
      resistant nocturnal polyuria. The sodium regulating hormones do not seem to
      mediate these processes. The overall effect in desmopressin nonresponders with
      nocturnal polyuria is variable. The extent to which indomethacin can be applied
      in the treatment of enuresis needs further evaluation.

PMID- 22999687
TI  - Long-term durability of the distal urethral polypropylene sling for the treatment
      of stress urinary incontinence: minimum 11-year followup.
AB  - PURPOSE: We report on the long-term outcomes of the distal urethral polypropylene
      sling for stress urinary incontinence in a patient cohort that was closely
      followed and whose outcomes were reported at 1 and 5 years after surgery.
      MATERIALS AND METHODS: We performed a prospective study of all consecutive
      patients who underwent a distal urethral polypropylene sling procedure between
      November 1999 and April 2000. The 1 and 5-year outcomes for this particular
      patient cohort were previously reported. At the minimum 11-year followup, outcome
      was determined by patient self-assessment including validated questionnaires.
      RESULTS: A total of 69 patients were followed prospectively and followup was
      obtained for 30. Of those lost to followup 10 were deceased and 5 were
      cognitively impaired. Mean patient age at followup was 73 years (range 40 to 97).
      More than 11 years after surgery 48% of patients reported no stress urinary
      incontinence symptoms and 63% were never bothered by stress urinary incontinence.
      Patients reported a mean overall symptom improvement of 64% compared to 81% at 5
      years. Overall 82% of patients met the criteria for treatment success by symptom
      scores and 80% met the criteria by bother scores. CONCLUSIONS: The distal
      urethral polypropylene sling procedure has excellent long-term durability in the
      treatment of stress urinary incontinence, in addition to low morbidity and low
      cost as previously described. Eleven years after the procedure the majority of
      patients report symptom improvement. Nevertheless, many older patients are unable
      to participate in followup. When choosing an anti-incontinence procedure,
      durability should be considered in light of patient age given that the
      theoretical advantages of long-term durability are limited by cognitive decline
      and mortality.

PMID- 22999688
TI  - Reporting quality of abstracts presented at the European Association of Urology
      meeting: a critical assessment.
AB  - PURPOSE: We assessed the reporting quality of randomized and nonrandomized,
      controlled trials presented in abstract form at the European Association of
      Urology annual meeting in a 10-year period and determined the impact on
      subsequent publication. MATERIALS AND METHODS: Abstracts presented at the
      European Association of Urology annual meetings in 1998, 1999, 2008 and 2009 were
      retrieved and included in analysis. Two 2-year meeting periods were considered,
      including 1) 1998 and 1999, and 2) 2008 and 2009. Two standardized forms were
      constructed based on the CONSORT (Consolidated Standards of Reporting Trials) and
      STROBE (Strengthening the Reporting of Observational studies in Epidemiology)
      guidelines, each including 15 and 16 items for randomized and nonrandomized,
      controlled trials, respectively. Reporting quality was assessed by measuring the
      proportion of items respected by authors when preparing the abstract, defined as
      the score ratio. Subsequent full-length publication within 2 years after the
      meeting was also determined by a PubMed(r) search. Differences between the 2
      periods were analyzed by the chi-square and simple t tests. Predictors of
      subsequent full-length publication were evaluated by multiple logistic regression
      using meeting period, topic, country of origin, design, multi-institutional study
      and the proportion of reported items (score ratio). RESULTS: A total of 3,139
      abstracts were included in analysis, of which 375 (11.9%) were randomized,
      controlled trials. Overall oncology represented the main topic (49.2% of all
      abstracts). The score ratio (proportion of adequately reported items in each
      abstract) was better for period 1 than 2 for randomized, controlled trials (63%
      vs 57%) but better for period 2 than 1 for nonrandomized, controlled trials
      (55.4% vs 53.2%, each p <0.001). Abstracts describing multi-institutional studies
      were more likely to be followed by full-length publication (OR 1.82, 95% CI 1.44
      2.30). Other features, including reporting quality (score ratio), did not predict
      subsequent publication. CONCLUSIONS: The reporting quality of European
      Association of Urology meeting abstracts did not improve in a decade.
      Nevertheless, this factor did not impact subsequent full-length publication.
      Ultimately, the reporting quality of abstracts remains to be improved by
      following currently available guidelines.

PMID- 22999689
TI  - The epidemiology of urinary incontinence in women with type 2 diabetes.
AB  - PURPOSE: Little research has been conducted on the epidemiology of urinary
      incontinence in individuals with type 2 diabetes. We examined prevalence,
      incidence and risk factors for urinary incontinence among women with type 2
      diabetes in the NHS (Nurses' Health Study) and NHS II. MATERIALS AND METHODS: We
      obtained urinary incontinence information at study baseline (2000 in NHS and 2001
      in NHS II) and 2 followup periods (2002 and 2004 in the NHS, and 2003 and 2005 in
      the NHS II). Among women with type 2 diabetes we calculated the prevalence of
      urinary incontinence for 9,994 women with baseline urinary incontinence
      information, and urinary incontinence incidence rates for 4,331 women with no
      urinary incontinence at baseline and urinary incontinence information during
      followup. Multivariable adjusted odds ratios and relative risks were estimated
      for associations between possible risk factors and urinary incontinence. RESULTS:
      The prevalence of at least monthly urinary incontinence was 48% and at least
      weekly urinary incontinence was 29% among women with type 2 diabetes, and the
      corresponding incidence rates were 9.1 and 3.4 per 100 person-years,
      respectively. White race, higher body mass index, higher parity, lower physical
      activity, current postmenopausal hormone use and diuretic use were risk factors
      for prevalent and incident urinary incontinence in this study, and hysterectomy,
      vascular disease and longer duration of diabetes were associated with increased
      odds of prevalent urinary incontinence only. Increasing age and microvascular
      complications were associated with a greater risk of frequent urinary
      incontinence. CONCLUSIONS: Urinary incontinence was common in this study of women
      with type 2 diabetes. We identified multiple risk factors for urinary
      incontinence in these women, several of which suggest ways to reduce urinary
      incontinence.

PMID- 22999690
TI  - Infection retardant coated inflatable penile prostheses decrease the incidence of
      infection: a systematic review and meta-analysis.
AB  - PURPOSE: This systematic review was done to compare the effectiveness of
      infection retardant coated inflatable penile prostheses vs noncoated devices.
      MATERIALS AND METHODS: We systematically reviewed PubMed(r) and Galileo(r) to
      identify all relevant case studies. The postoperative infection incidence rate
      was compared for coated and noncoated inflatable penile prostheses to determine
      whether coating the implant affects the rate of surgical implant infection.
      RESULTS: Included in analysis were 14 clinical case studies in a total of 9,910
      patients with a first time implant, including 5,214 inflatable penile prostheses
      without an infection retardant coating and 4,696 coated inflatable penile
      prostheses impregnated with minocycline/rifampin (3,158), rifampin/gentamycin
      immersion (181), vancomycin/gentamycin immersion (181) and a hydrophilic coating
      only (1,176). For noncoated vs coated prostheses the infection rate was 2.32% vs
      0.89% (p <0.01), including 0.63%, 0.55%, 4.42% and 1.11% for
      minocycline/rifampin, rifampin/gentamycin immersion, vancomycin/gentamycin
      immersion and hydrophilic coatings, respectively. CONCLUSIONS: This analysis
      documents a significant advantage of using coated compared to noncoated
      inflatable penile prostheses to prevent postoperative device infection. Infection
      retardant coatings that allow antibiotics to elute off the device components
      decrease the incidence of device infection by approximately 50%. Future studies
      must address novel techniques, such as preventing bacterial adhesion, to further
      decrease infectious etiologies.

PMID- 22999691
TI  - Editorial comment.

PMID- 22999692
TI  - Health related quality of life for monosymptomatic enuretic children and their
      mothers.
AB  - PURPOSE: There have been few reports addressing how nocturnal enuresis affects
      the health related quality of life of patients and their mothers. Thus, we
      evaluated the health related quality of life of enuretic children and their
      mothers. MATERIALS AND METHODS: The health related quality of life of 139
      patients with nocturnal enuresis and that of their mothers were evaluated before
      and after treatment. The children's health related quality of life was evaluated
      with the Kid-KINDL(r) protocol. The mothers' health related quality of life was
      evaluated using the SF-36(r), the SDS (Self-Rating Depression Scale) for rating
      depression and the STAI (State-Trait Anxiety Inventory) for assessing anxiety.
      RESULTS: In the health related quality of life of enuretic children, the family
      domain score was significantly lower than that of controls (p = 0.02). In the
      health related quality of life of the mothers as shown by SF-36, the vitality
      domain score was significantly lower compared to controls (p = 0.01). The
      evaluation of the STAI score demonstrated a higher state anxiety score (p =
      0.003), which represents current suffering from anxiety, and a similar trait
      anxiety score (p = 0.22), which represents a similar level of underlying tendency
      to anxiety. There was no significant difference between the mothers of enuretic
      children and the controls in the SDS evaluation. After treatment for enuresis the
      health related quality of life score was improved not only for the enuretic
      children as assessed by the Kid-KINDL protocol, but also for the mothers of
      enuretic children as assessed by the SF-36 and STAI. CONCLUSIONS: Similar to
      other pediatric chronic diseases, nocturnal enuresis is a condition that
      negatively affects the health related quality of life of children and their
      mothers. Impaired health related quality of life can be improved after the
      successful treatment of nocturnal enuresis.

PMID- 22999693
TI  - An operative performance rating system for urology residents.
AB  - PURPOSE: An operative performance rating system for urology residents was
      developed for 6 sentinel urological procedures. We tested the reliability,
      validity and feasibility of the operative performance rating system for urology
      residents. MATERIALS AND METHODS: The operative performance rating system of each
      procedure contained a 3-point case difficulty scale, 4 to 6 procedure specific
      items, 3 general items and an overall performance item. A Likert scale of 1 to 5
      was used for each item. A single video/audio record of each procedure was
      evaluated by the faculty. Single item interrater agreement was measured by
      comparing the observed variance and random measurement error variance. Resident
      operative performance evaluations were completed on line. Internal consistency
      reliability was measured using Cronbach alpha. Overall scale scores by resident
      training postgraduate year level were compared using 1-way ANOVA. RESULTS:
      Faculty evaluation of video/audio records showed an interrater agreement range of
      0.71 to 0.92. Faculty evaluations of resident operative performance demonstrated
      an internal consistency reliability range of 0.91 to 0.95. Significant
      differences in overall scale scores between postgraduate year levels were noted
      for 3 of the 6 procedures (p <=0.0016). CONCLUSIONS: An operative performance
      rating system for urology residents is feasible using an Internet based resident
      management system. Interrater agreement and internal consistency reliability meet
      threshold limits for checklist evaluation instruments. The operative performance
      rating system can discriminate among postgraduate year levels of resident
      training. A validated operative performance rating system can offer residents
      immediate, objective feedback on surgical performance and enable program
      directors to monitor progress in resident operative performance.

PMID- 22999694
TI  - How dry is "OAB-dry"? Perspectives from patients and physician experts.
AB  - PURPOSE: Overactive bladder is subtyped into overactive bladder-wet and
      overactive bladder-dry, based on the presence or absence, respectively, of
      urgency incontinence. To better understand patient and physician perspectives on
      symptoms among women with overactive bladder-wet and overactive bladder-dry, we
      performed patient focus groups and interviews with experts in urinary
      incontinence. MATERIALS AND METHODS: Five focus groups totaling 33 patients with
      overactive bladder symptoms, including 3 groups of overactive bladder-wet and 2
      groups of overactive bladder-dry patients, were conducted. Topics addressed
      patient perceptions of overactive bladder symptoms, treatments and outcomes. A
      total of 12 expert interviews were then done in which experts were asked to
      describe their views on overactive bladder-wet and overactive bladder-dry. Focus
      groups and expert interviews were transcribed verbatim. Qualitative data analysis
      was performed using grounded theory methodology, as described by Charmaz.
      RESULTS: During the focus groups sessions, women screened as overactive bladder
      dry shared the knowledge that they would probably leak if no toilet were
      available. This knowledge was based on a history of leakage episodes in the past.
      Those few patients with no history of leakage had a clinical picture more
      consistent with painful bladder syndrome than overactive bladder. Physician
      expert interviews revealed the belief that many patients labeled as overactive
      bladder-dry may actually be mild overactive bladder-wet. CONCLUSIONS: Qualitative
      data from focus groups and interviews with experts suggest that a spectrum exists
      between very mild overactive bladder-wet and severe overactive bladder-wet.
      Scientific investigations are needed to determine whether urgency without fear of
      leakage constitutes a unique clinical entity.

PMID- 22999695
TI  - Anatomical and manometric comparison of perineal and transscrotal approaches to
      artificial urinary sphincter placement.
AB  - PURPOSE: We compared cuff sites and assessed anatomical and manometric
      differences between the transscrotal and perineal approaches to artificial
      urinary sphincter placement in fresh male cadavers. MATERIALS AND METHODS:
      Artificial urinary sphincter implantation using perineal and transscrotal
      incisions was performed in 15 fresh male cadavers. The artificial urinary
      sphincter cuffs were placed as proximal as possible using each approach. After
      measuring urethral circumference at each cuff site, an appropriately sized cuff
      was placed at each location. The 61 to 70 cm H(2)O pressure reservoir and control
      pump were then connected to the cuffs. Retrograde leak point pressure was
      assessed sequentially across each cuff. The paired t test was used to compare
      urethral circumference and retrograde leak point pressure between the 2
      approaches. RESULTS: Mean urethral circumference using the perineal and
      transscrotal approaches was 5.38 (range 3.2 to 7.5) and 3.81 cm (range 3 to 4.5),
      respectively (p <0.0001, 95% CI of difference 0.99-2.13). Mean retrograde leak
      point pressure using the perineal and transscrotal approaches was 90.1 and 64.9
      cm H(2)O, respectively (p = 0.0002, 95% CI of difference 13.7-33.5). On visual
      inspection of cuff sites, the perineal approach was more proximal on the urethra
      than the transscrotal approach. CONCLUSIONS: While the transscrotal approach to
      artificial urinary sphincter placement has the advantage of technical ease, the
      anatomical and manometric findings of this cadaver study suggest that the
      perineal approach offers a more proximal cuff location, more robust urethral size
      and more effective urethral coaptation than the transscrotal approach.

PMID- 22999696
TI  - R.E.N.A.L. nephrometry score accurately predicts complications following
      laparoscopic renal cryoablation.
AB  - PURPOSE: The R.E.N.A.L. nephrometry is a standardized scoring system that
      quantifies the complexity of kidney tumors. We evaluated our experience with
      laparoscopic cryoablation and determined the ability of nephrometry to predict
      complications. MATERIALS AND METHODS: We reviewed the records of all patients who
      underwent laparoscopic cryoablation from July 2005 to February 2010 at 3
      institutions. The composite R.E.N.A.L. score was determined using preoperative
      imaging, and tumors were categorized as low (4-6), moderate (7-9) or high
      complexity (10-12). Perioperative data were analyzed to determine the presence of
      complications. The distribution of surgical complications and tumor categories
      was compared using the chi-square and Student's t test. Logistic regression was
      used to analyze the association between nephrometry score and postoperative
      complications. RESULTS: A total of 210 patients underwent laparoscopic
      cryoablation, 77 of whom had available preoperative imaging. Mean patient age was
      64.5 years and mean tumor size was 2.6 cm (range 1 to 4.5). Mean nephrometry
      score was 6.1 (range 4 to 12). Of the tumors 47 (61%) were categorized as low, 23
      (30%) as moderate and 7 (9%) as high complexity lesions. Overall there were 15
      (19.5%) complications, including 7 (9.5%) major and 8 (10%) minor complications.
      There was a significant difference in complication rates among the low (47
      patients, 0%), moderate (23 patients, 35%) and high complexity (7 patients, 100%)
      groups, respectively (p <0.001). On multivariate analysis nephrometry score was
      independently associated with a higher risk of postoperative complications (OR
      2.23, 95% CI 1.05-2.11, p = 0.008). CONCLUSIONS: In a multi-institutional cohort
      of patients undergoing laparoscopic cryoablation, the R.E.N.A.L. nephrometry
      score is independently associated with the occurrence of complications.
      Therefore, nephrometry can be used to successfully stratify patients in terms of
      anticipated risk of complications which, in turn, may help with surgical decision
      making.

PMID- 22999697
TI  - The impact of mechanical bowel preparation on postoperative complications for
      patients undergoing cystectomy and urinary diversion.
AB  - PURPOSE: The benefit of routine mechanical bowel preparation for patients
      undergoing radical cystectomy is not well established. We compared postoperative
      complications in patients who did or did not undergo mechanical bowel preparation
      before radical cystectomy. MATERIALS AND METHODS: In 2008 a single surgeon (GDS)
      performed open radical cystectomy with an ileal conduit or orthotopic neobladder
      in 105 consecutive patients with preoperative mechanical bowel preparation
      consisting of 4 l GoLYTELY(r). In 2009 radical cystectomy with an ileal conduit
      or orthotopic neobladder was performed in 75 consecutive patients without
      mechanical bowel preparation. A comprehensive database provided clinical,
      pathological and outcome data. RESULTS: All patients had complete perioperative
      data available. The 2 groups were similar in age, Charlson comorbidity score,
      diversion type, receipt of neoadjuvant radiation or chemotherapy, blood loss,
      hospital stay, time to diet and pathological stage. Postoperative urinary tract
      infection, wound dehiscence and perioperative death rates were similar in the 2
      groups. Clostridium difficile infection developed within 30 days of surgery in 11
      of 105 vs 2 of 75 patients with vs without mechanical bowel preparation (p =
      0.08). When adjusted for the annual hospital-wide C. difficile rate, the
      difference remained insignificant (p = 0.21). Clavien grade 3 or greater
      abdominal and gastrointestinal complications, including fascial dehiscence,
      abdominal abscess, small bowel obstruction, bowel leak and entero-diversion
      fistula, developed in 7 of 105 patients with (6.7%) vs 11 of 75 without (14.7%)
      mechanical bowel preparation (p = 0.08). CONCLUSIONS: The use of mechanical bowel
      preparation for patients undergoing radical cystectomy with an ileal conduit or
      orthotopic neobladder does not seem to impact the rates of perioperative
      infectious, wound and bowel complications. Larger series with multiple surgeons
      are necessary to confirm these findings.

PMID- 22999698
TI  - Population based trends in the surgical treatment of benign prostatic
      hyperplasia.
AB  - PURPOSE: Laser prostatectomy has increased in popularity in the last decade.
      However, traditional transurethral resection of the prostate remains common. To
      understand decisions about the use of laser prostatectomy vs transurethral
      prostate resection, we evaluated trends in transurethral surgery for benign
      prostatic hyperplasia in an all payer data set, focusing on patient and provider
      factors associated with the receipt of laser prostatectomy. MATERIALS AND
      METHODS: Using Florida State Inpatient Database and Ambulatory Surgery Database,
      we identified patients who underwent laser prostatectomy or transurethral
      prostate resection from 2001 to 2009. We calculated surgery rates with time,
      stratified by procedure type. We used multilevel regression to examine patient
      (age, race and comorbidity level) and provider (surgeon volume) factors
      associated with the receipt of laser prostatectomy vs transurethral prostate
      resection. RESULTS: While the overall rates of transurethral surgery remained
      stable during the study period (p = 0.227), laser prostatectomy use increased
      400% from 25 to 114 procedures per 100,000 men (p <0.001), replacing about half
      of all transurethral prostate resections. Patients were less likely to undergo
      laser prostatectomy if they were older (OR 0.65, 95% CI 0.61-0.70) and less
      healthy (OR 0.48, 95% CI 0.45-0.51). While these factors were predictive of
      surgery type, most of the variation in laser prostatectomy use (69%) was
      determined by the urologist seen by the patient. CONCLUSIONS: Laser prostatectomy
      use has increased in the last decade at the expense of transurethral prostate
      resection, driven largely by provider effects. However, elderly and more infirm
      patients are least likely to undergo it, raising concern about underuse in this
      population.

PMID- 22999699
TI  - How dry is dry? A review of definitions of continence in the contemporary
      exstrophy/epispadias literature.
AB  - PURPOSE: Definitions of continence following surgery in children with exstrophy
      epispadias complex vary widely. We assessed the most common definitions of
      continence and evaluated the clinical significance of usage patterns for those
      definitions. MATERIALS AND METHODS: We searched MEDLINE and EMBASE (2000 to 2011)
      for English language reports describing postoperative continence outcomes in
      children with exstrophy-epispadias complex. Articles were evaluated and data were
      abstracted by 2 reviewers. We assessed patient level factors such as age,
      preoperative diagnoses and use of additional therapies, as well as study level
      factors such as continence definition(s), country of origin and method of data
      collection. RESULTS: We identified 884 articles, of which 87 met inclusion
      criteria. In total these studies included continence outcomes data on 2,681
      patients (57% male). Only 59 studies (68%) clearly defined the term "continence."
      The most common definition of continence was dry with voiding/catheterization
      every 3 hours (used in 23 studies, or 39%, defining continence). There was no
      association between publication date (p = 0.17), study location (p = 0.47) or
      study size (p = 0.81) and continence definition. There was a trend toward
      improved reporting of methods for continence ascertainment in more recent years
      (p = 0.02). Of the 2,681 children included 1,372 (51%) were dry by the definition
      used in their study. CONCLUSIONS: The most frequent definition of continence was
      "dryness with voiding or catheterization at 3-hour intervals." However,
      definitions were highly variable and many authors did not define continence at
      all. To better define outcomes, we recommend that a standardized definition of
      continence be established and used in future reports.

PMID- 22999700
TI  - A randomized clinical study of circumcision with a ring device versus
      conventional circumcision.
AB  - PURPOSE: We investigated the safety and efficacy of Shang RingTM male
      circumcision and conventional sleeve resection circumcision in a randomized
      study. MATERIALS AND METHODS: During the same period, 479 cases of Shang Ring
      circumcision and 354 of sleeve resection circumcision were performed. Complete
      followup data were evaluated on the 2 groups. Operative time, pain score, blood
      loss, postoperative complications, wound healing time and treatment costs were
      compared. RESULTS: There was no statistically significant difference in average
      age and foreskin status between the 2 groups preoperatively (p >0.05). Compared
      to the conventional group, there were shorter operative time, less blood loss and
      a lower intraoperative pain score in the ring group (p <0.05). In addition, ring
      male circumcision showed a lower complication rate than conventional circumcision
      (6.89% vs 13.28%, p = 0.002). However, wound healing time in the ring group was
      longer than in the conventional group (mean +/- SD 19.86 +/- 5.24 vs 13.42 +/-
      2.35 days, p <0.001). CONCLUSIONS: Shang Ring male circumcision is a safe,
      efficient procedure with a relatively low complication rate and high patient
      satisfaction. It may be worthwhile to popularize this method, especially in
      countries where the general population has low to limited resources.

PMID- 22999701
TI  - The value of sonoelastography scores and the strain ratio in differential
      diagnosis of azoospermia.
AB  - PURPOSE: We evaluated the diagnostic performance of real-time elastography for
      differentiating nonobstructive from obstructive azoospermia. MATERIALS AND
      METHODS: We evaluated 1,192 testes, including 584 with nonobstructive
      azoospermia, 408 with obstructive azoospermia and 200 controls, from men with a
      mean +/- SD age of 30 +/- 5 years. Two radiologists evaluated the testes using a
      5-degree elastography score system. The strain ratio was calculated on line. Of
      156 azoospermic testes 78 were diagnosed by bilateral testicular biopsy for
      diagnostic purposes or sperm harvesting. RESULTS: In our software system a score
      of 3 indicated average strain, and scores 4 and 5 indicated low strain. Average
      or low strain (score 3 to 5) was seen in 477 of 584 testes with nonobstructive
      azoospermia (81.7%). This rate was significantly higher than the rate in
      obstructive azoospermic and control testes (68 of 408 or 16.3% and 30 of 200 or
      15.0%, p <0.001). The strain ratio significantly differed for nonobstructive and
      obstructive azoospermia (median 0.490 and 0.340, Z = -20.560, p <0.001).
      CONCLUSIONS: Real-time elastography is a promising imaging method with great
      potential for the differential diagnosis of azoospermia.

PMID- 22999702
TI  - Editorial comment.

PMID- 22999703
TI  - Evaluation of endoscopic laser excision of polypropylene mesh/sutures following
      anti-incontinence procedures.
AB  - PURPOSE: We reviewed our experience with and outcome of the largest series to our
      knowledge of patients who underwent endoscopic laser excision of eroded
      polypropylene mesh or sutures as a complication of previous anti-incontinence
      procedures. MATERIALS AND METHODS: A total of 12 female patients underwent
      endoscopic laser excision of suture/mesh erosions at 1 center during a 10-year
      period. Primary outcome variables were the requirement of additional endoscopic
      or open surgery to remove mesh/sutures. Secondary outcome variables were
      persistence of urinary symptoms, postoperative complications, continence status
      and requirement of additional anti-incontinence procedures. RESULTS: The mean
      interval from previous surgery to erosion was 59 months (range 7 to 144) and the
      duration of presenting symptoms ranged from 3 to 84 months (mean 19). Ten
      patients underwent endoscopic excision of the mesh/suture with the holmium:YAG
      laser and 2 underwent excision with the thulium laser. Mean operative duration
      was 19 minutes (range 10 to 25) and followup was 65.5 months (range 6 to 134).
      Postoperatively 6 patients remain asymptomatic and 2 required a rectus fascial
      sling for recurrent stress urinary incontinence. Four patients underwent a second
      endoscopic excision due to minor persistence of erosion. Only 1 patient
      ultimately required open cystotomy to remove the eroded biomaterial. No
      intraoperative complications were recorded and all patients are currently
      asymptomatic. CONCLUSIONS: Endoscopic laser excision is an acceptable first line
      approach for the management of eroded biomaterials due to its high long-term
      success rate and minimally invasive nature.

PMID- 22999704
TI  - Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells
      enhances binding of LDL to proteoglycans.
AB  - OBJECTIVE: Calcific aortic valve disease is a progressive condition that shares
      some common pathogenic features with atherosclerosis. Transforming growth factor
      beta1 is a recognized mediator of atherosclerosis and is expressed in aortic
      valve lesions. Transforming growth factorbeta1 stimulates glycosaminoglycan
      elongation of proteoglycans that is associated with increased lipid binding. We
      investigated the presence of transforming growth factor-beta1 and downstream
      signaling intermediates in diseased human aortic valves and the effects of
      activated transforming growth factor-beta1 receptor signaling on aortic valve
      interstitial cell proteoglycan synthesis and lipid binding as a possible
      mechanism for the initiation of the early lesion of calcific aortic valve
      disease. METHODS AND RESULTS: Diseased human aortic valve leaflets demonstrated
      strong immunohistochemical staining for transforming growth factor-beta1 and
      phosphorylated Smad2/3. In primary porcine aortic valve interstitial cells,
      Western blots showed that transforming growth factor-beta1 stimulated
      phosphorylation in both the carboxy and linker regions of Smad2/3, which was
      inhibited by the transforming growth factor-beta1 receptor inhibitor SB431542.
      Gel electrophoresis and size exclusion chromatography demonstrated that SB431542
      decreased transforming growth factor-beta1-mediated [(35)S]-sulfate incorporation
      into proteoglycans in a dose-dependent manner. Further, in proteoglycans derived
      from transforming growth factor-beta1-treated valve interstitial cells, gel
      mobility shift assays demonstrated that inhibition of transforming growth factor
      beta1 receptor signaling resulted in decreased lipid binding. CONCLUSIONS:
      Classic transforming growth factor-beta1 signaling is present in human aortic
      valves in vivo and contributes to the modification of proteoglycans expressed by
      valve interstitial cells in vitro. These findings suggest that transforming
      growth factor-beta1 may promote increased low-density lipoprotein binding in the
      early phases of calcific aortic valve disease.

PMID- 22999705
TI  - Complement, interferon and lupus.
AB  - The complement pathway was implicated in the immunopathogenesis of lupus and
      other autoimmune disorders decades ago. The apparent paradox that early
      complement component (C1q, C2 and C4) deficiencies predispose to lupus has been
      explained by the beneficial roles of these proteins in promoting the clearance of
      immune complexes (ICs) and apoptotic cells. Recent findings demonstrate that, in
      the absence of C1q, instead of ICs binding to monocytes, they preferentially
      engage plasmacytoid dendritic cells (pDC) so generating interferon (IFN) alpha,
      the cytokine with potent immune adjuvant properties. C1q opsonized apoptotic
      cells also exert an immunosuppressive effect through cytokine regulation and the
      stimulation of additional opsonins by macrophages. C1q was recently reported to
      impede neutrophil extracellular trap (NET) degradation. NETs are known to promote
      type I IFN production in SLE by providing a source of antigen for the formation
      of ICs as well as through direct pDC activation by cathelicidin (LL37). Together,
      these findings provide both direct and indirect links between two key pathways
      implicated in lupus pathogenesis: complement and IFN.

PMID- 22999706
TI  - Mercury, arsenic and selenium exposure levels in relation to fish consumption in
      the Mediterranean area.
AB  - In order to assess mercury (Hg), selenium (Se) and arsenic (As) exposure in the
      Mediterranean area, total mercury (THg), monomethylmercury (MeHg), Se and As
      levels were measured in umbilical cord blood and breast milk from Italian
      (n=900), Slovenian (n=584), Croatian (n=234) and Greek (n=484) women. THg, MeHg,
      As, and Se levels were also determined in blood samples of the same mothers from
      Italy and Croatia. In addition, THg and MeHg were determined in the same women's
      hair from all the countries involved in this study and As and Se levels were
      determined in the mother's urine samples from Italy, Croatia and Greece. Besides
      recording the consumption of other food items, the frequencies of fish
      consumption were assessed by detailed food frequency questionnaires, since fish
      represents an important source of Hg, Se and As in humans. The highest levels of
      THg and As were found in cord blood (Med((THg))=5.8 ng/g; Med((As))=3.3 ng/g) and
      breast milk (Med((THg))=0.6 ng/g; Med((As))=0.8 ng/g) from Greek women, while the
      highest Se levels were found in cord blood (Med=113 ng/g) from Italy. Significant
      linear correlations were found between Hg, Se and As in blood, cord blood and
      breast milk. In addition, significant relations were found between the
      frequencies of total fish consumption and biomarkers of As, MeHg and Se exposure,
      with the strongest Spearman rank coefficients between frequencies of total fish
      consumption and THg levels in cord blood (r(s)=0.442, p<0.001) or THg levels in
      hair (r(s)=0.421, p<0.001), and between frequencies of total fish consumption and
      As levels in cord blood (r(s)=0.350, p<0.001). The differences in Hg and As
      exposure between countries were probably due to different amounts of fish
      consumption and the consumption of different species of fish of different origin,
      while the highest Se levels in women from Italy were probably the consequence of
      the more frequent consumption of different non specific food items. Moreover,
      fish consumption, the possible common source of As, Hg and Se intake, could
      explain the correlations between the elements determined in cord blood, mother's
      blood or breast milk.

PMID- 22999707
TI  - Persistent pollutants: a brief history of the discovery of the widespread
      toxicity of chlorinated hydrocarbons.
AB  - Rachel Carson's Silent Spring is often depicted as the beginning of a broad
      societal concern about the dangers of DDT and other pesticides. Attention to the
      other chlorinated hydrocarbons, specifically PCBs, is seen as an outgrowth of the
      late 1960s environmental movement. Carson's work was clearly critical in
      broadening the history to include the environmental impact and set the stage for
      the path breaking work decades later by Theo Colburn and others on endocrine
      disruptions associated with other synthetic chemicals. This article reviews the
      development of the understanding the dangers of the chlorinated hydrocarbons in
      the decades preceding Carson's book. Although little noticed, Rachel Carson makes
      this observation herself.

PMID- 22999708
TI  - Vibrational spectral investigation and Natural Bond Orbital analysis of anti
      rheumatoid drug ethyl 4-nitrophenylacetate--DFT approach.
AB  - Vibrational analysis of ethyl 4-nitrophenylacetate (ENPA) molecule was carried
      out using FT-IR and FT-Raman spectroscopic techniques. The equilibrium geometry,
      harmonic vibrational wave numbers, various bonding features have been computed
      using density functional theory. The calculated molecular geometry parameters
      have been compared with XRD data. The detailed interpretation of the vibrational
      spectra has been carried out by computing Potential Energy Distribution (PED).
      Stability of the molecule arising from hyperconjugative interactions and charge
      delocalization has been analyzed using Natural Bond Orbital (NBO) analysis. The
      results show that the charge in the electron density (ED) in the sigma(*) and
      pi(*) antibonding orbitals and second order delocalization energies (E(2))
      confirm the occurrence of ICT (intramolecular charge transfer) within the
      molecule. The simulated spectra satisfactorily coincide with the experimental
      spectra.

PMID- 22999709
TI  - Atrazine disrupts steroidogenesis, VEGF and NO production in swine granulosa
      cells.
AB  - Atrazine is one of the most widely employed herbicides. Due to its environmental
      persistence, it can be detected in ground and water thus becoming the subject of
      a serious concern because of its potential endocrine disrupting activity. In
      particular, several in vitro and in vivo studies point out adverse effects on
      reproduction. However, these data were mainly collected in the male, while
      studies on females are lacking. Present work was therefore set up on swine
      ovarian granulosa cells to investigate the effect of atrazine on steroidogenesis
      and proliferation. Moreover, since vessel growth is fundamental for reproductive
      function, we evaluated the herbicide's effect on two of the main angiogenesis
      signaling molecules, VEGF and NO. Our data show that atrazine markedly interferes
      with steroidogenesis while it does not modify cell proliferation; in addition,
      the herbicide has also been found to affect the production of the examined
      angiogenesis molecules. Collectively, these results indicate for the first time a
      potential negative effect of atrazine on ovarian functions in the swine species.

PMID- 22999710
TI  - Malignant fibrous histiocytoma of the head and neck: a case series.
AB  - PURPOSE: The study objective is to evaluate the clinical features and outcomes of
      patients treated for head and neck malignant fibrous histiocytoma at a tertiary
      care medical facility. MATERIALS AND METHODS: This is a retrospective case series
      of 17 adult subjects with malignant fibrous histiocytoma of the head and neck who
      were treated between January 1, 1965, and December 31, 2010. This study was
      conducted using patient charts at a tertiary medical center. Subject selection
      was conducted using Current Procedural Terminology numbers; International
      Classification of Diseases, Ninth Revision, codes; and a search of the tumor
      registry. RESULTS: Chart review of the 17 identified subjects revealed an
      overwhelming male predominance (88%) with an overall mean age of 69 years(52-87
      years). Thirteen patients (78%) underwent some form of surgical resection, 6
      patients (35%) received radiation therapy, and 6 (35%) were given chemotherapy
      over the course of treatment. Nine tumors (53%) had a cutaneous origin, whereas 8
      lesions (47.1%) were found in the soft tissue of the head and neck region. The
      local recurrence rate following a single resection was 46%. Overall median
      survival following diagnosis was found to be 65 months, with a 5-year survival
      rate of 52%. Median disease-free survival was 20 months, with a 5-year disease
      free survival rate of 37%. Overall median and 5-year survival rates were found to
      increase with clear surgical margins, as was 5-year survival. CONCLUSIONS:
      Aggressive surgical management to achieve clear margins is central to the
      effective treatment of malignant fibrous histiocytoma of the head and neck.
      Metastatic disease portends a dismal prognosis.

PMID- 22999711
TI  - Prospects of personalized medicine in cardiovascular diseases.
AB  - Cardiovascular diseases remain the dominant cause of death worldwide. In the last
      decades, the remarkable advances in human genetic and genomic research, plus the
      now common use of genome-wide association studies, have led to the identification
      of numerous genetic variants associated with specific cardiovascular traits and
      diseases. Although the clinical applications are limited because the genetic risk
      of common cardiovascular disease is still unexplained, and the mechanisms of
      action of the genetic factor(s) are not known, these research advances have, in
      turn, widely opened the concept of personalized medicine. In this paper, the
      status and prospects of personalized medicine for cardiovascular disease will be
      presented. This will be followed by a discussion of issues regarding the
      implementation of personalized medicine.

PMID- 22999712
TI  - Personalized medicine strategies for managing patients with parkinsonism and
      cognitive deficits.
AB  - Patients exhibiting the classic manifestations of parkinsonism - tremors,
      rigidity, postural instability, slowed movements and, sometimes, sleep
      disturbances and depression - may also display severe cognitive disturbances. All
      of these particular motoric and behavioral symptoms may arise from Parkinson's
      disease [PD] per se, but they can also characterize Lewy Body dementia [LBD] or
      concurrent Parkinson's and Alzheimer's diseases [PD & AD]. Abnormalities of both
      movement and cognition are also observed in numerous other neurologic diseases,
      for example Huntington's Disease and the frontotemporal dementia. Distinguishing
      among these diseases in an individual patient is important in "personalizing" his
      or her mode of treatment, since an agent that is often highly effective in one of
      the diagnoses (e.g., L-dopa or muscarinic antagonists in PD) might be ineffective
      or even damaging in one of the others. That such personalization, based on
      genetic, biochemical, and imaging-based biomarkers, is feasible is suggested by
      the numerous genetic abnormalities already discovered in patients with
      parkinsonism, Alzheimer's disease and Huntington's disease (HD) and by the
      variety of regional and temporal patterns that these diseases can produce, as
      shown using imaging techniques.

PMID- 22999713
TI  - Pathophysiology and management strategies for hyperglycemia for patients with
      acute illness during and following a hospital stay.
AB  - Hyperglycemia in the inpatient setting is associated with poor clinical outcomes
      and is often suboptimally managed. This review addresses the pathophysiology of
      hyperglycemia, current recommendations for management of inpatient hyperglycemia
      in the general medical and surgical care setting, the transition between
      different diabetes treatments, and the transition from inpatient to outpatient
      therapy. The preferred drug for management of inpatient hyperglycemia is insulin.
      Successful use of intravenous and subcutaneous insulin in the hospital is based
      on the implementation of standardized protocols. Current guidelines recommend
      basal-bolus subcutaneous insulin in non-critically ill patients. The methods of
      switching from intravenous to subcutaneous, sliding-scale to basal-bolus, and
      biphasic to basal-bolus are discussed. Transition from an inpatient to an
      outpatient insulin regimen, especially in patients new to insulin therapy,
      requires special attention to ensure that patients have the knowledge to
      administer insulin safely and effectively. The optimal regimen at discharge must
      be individualized. Patients with acute infections may benefit from insulin
      therapy until the infection is resolved. Strategies to optimize diabetes therapy
      after discharge are discussed. Prompt outpatient follow-up is crucial to ensure
      optimal glycemic control. Despite the challenges, improved glycemic control in
      individuals with acute illness has the potential to reduce morbidity and
      mortality in individuals with this widespread metabolic illness.

PMID- 22999715
TI  - Dual antiplatelet therapy after drug-eluting stent implantation: is it time to
      slacken the reins?

PMID- 22999714
TI  - Basic principles of tumor-associated regulatory T cell biology.
AB  - Due to the critical role of forkhead box (Fox)p3(+) regulatory T cells (Tregs) in
      the regulation of immunity and the enrichment of Tregs within many human tumors,
      several emerging therapeutic strategies for cancer involve the depletion or
      modulation of Tregs, with the aim of eliciting enhanced antitumor immune
      responses. Here, we review recent advances in understanding of the fundamental
      biology of Tregs, and discuss the implications of these findings for current
      models of tumor-associated Treg biology. In particular, we discuss the context
      dependent functional diversity of Tregs, the developmental origins of these
      cells, and the nature of the antigens that they recognize within the tumor
      environment. In addition, we highlight critical areas of focus for future
      research.

PMID- 22999716
TI  - Double antiplatelet therapy after drug-eluting stent implantation: risk
      associated with discontinuation within the first year.
AB  - OBJECTIVES: The goal of this study was to assess the risk associated with double
      antiplatelet therapy (DAT) discontinuation, and specifically, temporary
      discontinuation, during the first year after drug-eluting stent (DES)
      implantation. BACKGROUND: Doubts remain about the risk of temporary DAT
      discontinuation within 1 year after DES implantation. METHODS: A total of 1,622
      consecutive patients undergoing DES implantation at 29 hospitals were followed up
      at 3, 6, 9, and 12 months to record the 1-year antiplatelet therapy
      discontinuation (ATD) rate, the number of days without DAT, and the rate of 1
      year major cardiac events. Cox regression was used to analyze the association
      between ATD considered as a time-dependent covariate and 1-year cardiac events.
      RESULTS: One hundred seventy-two (10.6%) patients interrupted at least 1
      antiplatelet drug during the first year after DES implantation, although only 1
      during the first month. Most (n=111, 64.5%) interrupted DAT temporarily (median:
      7 days; range: 5 to 8.5): 79 clopidogrel (31 temporarily), 38 aspirin (27
      temporarily), and 55 both drugs (53 temporarily). Discontinuation was followed by
      acute coronary syndrome in 7 (4.1%; 95% confidence interval [CI]: 1.7 to 8.2), a
      similar rate of major cardiac events to that in patients without ATD (n=80; 5.5%;
      95% CI: 4.4 to 6.8; p=0.23). ATD was not independently associated with 1-year
      major cardiac events (hazard ratio: 1.32 [95% CI: 0.56 to 3.12]). CONCLUSIONS:
      ATD within the first year and beyond the first month after DES is not
      exceptional, is usually temporary, and does not appear to have a large impact on
      risk.

PMID- 22999717
TI  - A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial
      (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor
      zotarolimus-eluting stent implantation).
AB  - OBJECTIVES: The goal of this study was to evaluate shorter duration (3 months)
      dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation.
      BACKGROUND: There have been few published reports of prospective randomized
      clinical studies comparing the safety and efficacy of shorter duration DAPT after
      DES implantation. METHODS: We randomly assigned 2,117 patients with coronary
      artery stenosis into 2 groups according to DAPT duration and stent type: 3-month
      DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3
      month DAPT, n=1,059) versus 12-month DAPT following the other DES implantation
      (standard therapy, n=1,058). We hypothesized that the E-ZES+3-month DAPT would be
      noninferior to the standard therapy for the primary composite endpoint
      (cardiovascular death, myocardial infarction, stent thrombosis, target?vessel
      revascularization, or bleeding) at 1 year. RESULTS: The primary endpoint occurred
      in 40 (4.7%) patients assigned to E-ZES+3-month DAPT compared with 41 (4.7%)
      patients assigned to the standard therapy (difference: 0.0%; 95% confidence
      interval [CI]: -2.5 to 2.5; p=0.84; p<0.001 for noninferiority). The composite
      rates of any death, myocardial infarction, or stent thrombosis were 0.8% and
      1.3%, respectively (difference: -0.5%; 95% CI: -1.5 to 0.5; p=0.48). The rates of
      stent thrombosis were 0.2% and 0.3%, respectively (difference: -0.1%; 95% CI: 
      0.5 to 0.3; p=0.65) without its further occurrence after cessation of clopidogrel
      in the E-ZES+3-month DAPT group. The rates of target vessel revascularization
      were 3.9% and 3.7%, respectively (difference: 0.2%; 95% CI: -2.3 to 2.6; p=0.70).
      CONCLUSIONS: E-ZES+3-month DAPT was noninferior to the standard therapy with
      respect to the occurrence of the primary endpoint. (REal Safety and Efficacy of a
      3-month dual antiplatelet Therapy following E-ZES implantation [RESET];
      NCT01145079).

PMID- 22999718
TI  - Radiofrequency ablation of premature ventricular ectopy improves the efficacy of
      cardiac resynchronization therapy in nonresponders.
AB  - OBJECTIVES: This study sought to examine whether suppressing premature
      ventricular contractions (PVC) using radiofrequency ablation improves
      effectiveness of the cardiac resynchronization therapy (CRT) in nonresponders.
      BACKGROUND: CRT is an effective strategy for drug refractory congestive heart
      failure. However, one-third of patients with CRT do not respond clinically, and
      the causes for nonresponse are poorly understood. Whether frequent PVC contribute
      to CRT nonresponse remains unknown. METHODS: In this multicenter study, CRT
      nonresponders with >10,000 PVC in 24 h who underwent PVC ablation were enrolled
      from a prospective database. RESULTS: Sixty-five subjects (age 66.6 +/- 12.4
      years, 78% men, QRS duration of 155 +/- 18 ms) had radiofrequency ablation of PVC
      from 76 foci. Acute and long-term success rates of ablation were 91% and 88% in
      12 +/- 4 months of follow-up. There was significant improvement in left
      ventricular (LV) ejection fraction (26.2 +/- 5.5% to 32.7 +/- 6.7 %, p < 0.001),
      LV end-systolic diameter (5.93 +/- 0.55 cm to 5.62 +/- 0.32 cm, p < 0.001), LV
      end-diastolic diameter (6.83 +/- 0.83 cm to 6.51 +/- 0.91 cm, p < 0.001), LV end
      systolic volume (178 +/- 72 to 145 +/- 23 ml, p < 0.001), LV end-diastolic volume
      (242 +/- 85 ml to 212 +/- 63 ml, p < 0.001), and median New York Heart
      Association functional class (3.0 to 2.0, p < 0.001). Modeling of pre-ablation
      PVC burden revealed an improvement in ejection fraction when the pre-ablation PVC
      burden was >22% in 24 h. CONCLUSIONS: Frequent PVC is an uncommon yet significant
      cause of CRT nonresponse. Radiofrequency ablation of PVC foci improves LV
      function and New York Heart Association class and promotes reverse remodeling in
      CRT nonresponders. PVC ablation may be used to enhance CRT efficacy in
      nonresponders with significant PVC burden.

PMID- 22999720
TI  - Lessons from the past and promises for the future for carotid intima-media
      thickness.
AB  - Carotid intima-media thickness (CIMT) measurements have been used in
      cardiovascular research for more than 2 decades. There is a wealth of evidence
      showing that CIMT can be assessed in a reproducible manner and that increased
      CIMT relates to unfavorable risk factor levels and atherosclerosis elsewhere in
      the arterial system and to the risk of vascular events. Change in CIMT over time
      can be readily assessed, and trials showed that the rate of change is modifiable
      by treatment. Several issues important for the cardiovascular research community
      and its application in clinical practice are still outstanding. Promising future
      areas for CIMT measurements are: 1) application in studies among children and
      adolescents; 2) use of CIMT trials positioned decisively before the start of a
      morbidity and mortality trial; and 3) the use of CIMT measurement in risk
      stratification in those with an intermediate 10-year risk estimate.

PMID- 22999719
TI  - Measurements of carotid intima-media thickness and of interadventitia common
      carotid diameter improve prediction of cardiovascular events: results of the
      IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors
      of Vascular Events in a High Risk European Population) study.
AB  - OBJECTIVES: The goal of this study was to compare the performance of several
      measures of carotid intima-media thickness (C-IMT) as predictors of
      cardiovascular events (CVEs), and to investigate whether they add to the
      predictive accuracy of Framingham risk factors (FRFs). BACKGROUND: Various
      markers of subclinical atherosclerosis have been identified as predictors of
      CVEs, but the most powerful variable is still under debate. METHODS: A cohort
      study was carried out in 5 European countries. A total of 3,703 subjects (median
      age 64.4 years; 48% men) were followed-up for a median of 36.2 months, and 215
      suffered a first CVE (incidence: 19.9/1,000 person-years). RESULTS: All measures
      of C-IMT and the interadventitia common carotid artery diameter (ICCAD) were
      associated with the risk of CVEs, after adjustment for FRFs and therapies (all p
      < 0.005). The average of 8 maximal IMT measurements (IMT(mean-max)), alone or
      combined with ICCAD, classified events and non-events better than the common
      carotid mean IMT (net reclassification improvement [NRI]: +11.6% and +19.9%,
      respectively; both p < 0.01). Compared with classification based on FRFs alone,
      the NRI resulting from the combination of FRFs+ICCAD+IMT(mean-max) was +12.1% (p
      < 0.01). The presence of at least 1 plaque (maximum IMT >1.5 mm) performed
      significantly worse than composite IMTs that incorporated plaques (p < 0.001).
      Adjusted Kaplan-Meier curves showed that individuals with a FRS = 22.6% (cohort
      average), and both IMT(mean-max) and ICCAD above the median, had a 6.5% risk to
      develop a CVE over 3 years versus a 3.4% risk for those with the same FRS, and
      both IMT(mean-max) and ICCAD below the median. CONCLUSIONS: A risk stratification
      strategy based on C-IMT and ICCAD as an adjunct to FRFs is a rational approach to
      prevention of cardiovascular disease.

PMID- 22999721
TI  - Quantification of myocardial perfusion and myocardial perfusion reserve by
      positron emission tomography and cardiovascular magnetic resonance imaging.

PMID- 22999722
TI  - Quantification of absolute myocardial perfusion in patients with coronary artery
      disease: comparison between cardiovascular magnetic resonance and positron
      emission tomography.
AB  - OBJECTIVES: The aim of this study was to compare fully quantitative
      cardiovascular magnetic resonance (CMR) and positron emission tomography (PET)
      myocardial perfusion and myocardial perfusion reserve (MPR) measurements in
      patients with coronary artery disease (CAD). BACKGROUND: Absolute quantification
      of myocardial perfusion and MPR with PET have proven diagnostic and prognostic
      roles in patients with CAD. Quantitative CMR perfusion imaging has been
      established more recently and has been validated against PET in normal hearts.
      However, there are no studies comparing fully quantitative CMR against PET
      perfusion imaging in patients with CAD. METHODS: Forty-one patients with known or
      suspected CAD prospectively underwent quantitative (13)N-ammonia PET and CMR
      perfusion imaging before coronary angiography. RESULTS: The CMR-derived MPR
      (MPR(CMR)) correlated well with PET-derived measurements (MPR(PET)) (r = 0.75, p
      < 0.0001). MPR(CMR) and MPR(PET) for the 2 lowest scoring segments in each
      coronary territory also correlated strongly (r = 0.79, p < 0.0001). Absolute CMR
      perfusion values correlated significantly, but weakly, with PET values both at
      rest (r = 0.32; p = 0.002) and during stress (r = 0.37; p < 0.0001). Area under
      the receiver-operating characteristic curve for MPR(PET) to detect significant
      CAD was 0.83 (95% confidence interval: 0.73 to 0.94) and for MPR(CMR) was 0.83
      (95% confidence interval: 0.74 to 0.92). An MPR(PET) <=1.44 predicted significant
      CAD with 82% sensitivity and 87% specificity, and MPR(CMR) <=1.45 predicted
      significant CAD with 82% sensitivity and 81% specificity. CONCLUSIONS: There is
      good correlation between MPR(CMR) and MPR(PET.) For the detection of significant
      CAD, MPR(PET) and MPR(CMR) seem comparable and very accurate. However, absolute
      perfusion values from PET and CMR are only weakly correlated; therefore, although
      quantitative CMR is clinically useful, further refinements are still required.

PMID- 22999723
TI  - Endothelial dysfunction, arterial stiffness, and heart failure.
AB  - Outcomes for heart failure (HF) patients remain suboptimal. No known therapy
      improves mortality in acute HF and HF with preserved ejection fraction; the most
      recent HF trial results have been negative or neutral. Improvement in surrogate
      markers has not necessarily translated into better outcomes. To translate
      breakthroughs with potential therapies into clinical benefit, a better
      understanding of the pathophysiology establishing the foundation of benefit is
      necessary. Vascular function plays a central role in the development and
      progression of HF. Endothelial function and nitric oxide availability affect
      myocardial function, systemic and pulmonary hemodynamics, and coronary and renal
      circulation. Arterial stiffness modulates ventricular loading conditions and
      diastolic function, key components of HF with preserved ejection. Endothelial
      function and arterial stiffness may therefore serve as important physiological
      targets for new HF therapies and facilitate patient selection for improved
      application of existing agents.

PMID- 22999724
TI  - R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated
      cardiomyopathy.
AB  - OBJECTIVES: The goal of this study was to characterize a variant in the SCN5A
      gene that encodes the alpha-subunit of the cardiac sodium channel, Nav1.5, which
      was identified in 1 large kindred with dilated cardiomyopathy (DCM) and multiple
      arrhythmias, including premature ventricular complexes (PVCs). BACKGROUND:
      Treatment guidelines for familial DCM are based on conventional heart failure
      therapies, and no gene-based interventions have been established. METHODS: Family
      members underwent clinical evaluation and screening of the SCN5A and LMNA genes.
      Cellular electrophysiology and computational modeling were used to determine the
      functional consequences of the mutant Nav1.5 protein. RESULTS: An R222Q missense
      variant located in a Nav1.5 voltage-sensing domain was identified in affected
      family members. Patch-clamp studies showed that R222Q Nav1.5 did not alter sodium
      channel current density, but did left shift steady-state parameters of activation
      and inactivation. Using a voltage ramp protocol, normalized current responses of
      R222Q channels were of earlier onset and greater magnitude than wild-type
      channels. Action potential modeling using Purkinje fiber and ventricular cell
      models suggested that rate-dependent ectopy of Purkinje fiber origin is the
      predominant ventricular effect of the R222Q variant and a potential cause of DCM.
      In R222Q carriers, there were only modest responses to heart failure therapies,
      but PVCs and DCM were substantially reduced by amiodarone or flecainide, which
      are drugs that have sodium channel-blocking properties. CONCLUSIONS: The R222Q
      SCN5A variant has an activating effect on sodium channel function and is
      associated with reversible ventricular ectopy and DCM. Elucidation of the genetic
      basis of familial DCM can enable effective gene-targeted therapy to be
      implemented.

PMID- 22999725
TI  - The National Cardiovascular Data Registry (NCDR) Data Quality Brief: the NCDR
      Data Quality Program in 2012.
AB  - OBJECTIVES: The National Cardiovascular Data Registry (NCDR) developed the Data
      Quality Program to meet the objectives of ensuring the completeness, consistency,
      and accuracy of data submitted to the observational clinical registries. The Data
      Quality Program consists of 3 main components: 1) a data quality report; 2) a set
      of internal quality assurance protocols; and 3) a yearly data audit program.
      BACKGROUND: Since its inception in 1997, the NCDR has been the basis for the
      development of performance and quality metrics, site-level quality improvement
      programs, and peer-reviewed health outcomes research. METHODS: Before inclusion
      in the registry, data are filtered through the registry-specific algorithms that
      require predetermined levels of completeness and consistency for submitted data
      fields as part of the data quality report. Internal quality assurance protocols
      enforce data standards before reporting. Within each registry, 300 to 625 records
      are audited annually in 25 randomly identified sites (i.e., 12 to 25 records per
      audited site). RESULTS: In the 2010 audits, the participant average raw accuracy
      of data abstraction for the CathPCI Registry, ICD Registry, and ACTION Registry
      GWTG were, respectively, 93.1% (range, 89.4% minimum, 97.4% maximum), 91.2%
      (range, 83.7% minimum, 95.7% maximum), and 89.7.% (range, 85% minimum, 95%
      maximum). CONCLUSIONS: The 2010 audits provided evidence that many fields in the
      NCDR accurately represent the data from the medical charts. The American College
      of Cardiology Foundation is undertaking a series of initiatives aimed at creating
      a quality assurance rapid learning system, which, when complete, will monitor,
      evaluate, and improve data quality.

PMID- 22999726
TI  - Long-term exercise training and adherence: it is not just exercise.

PMID- 22999727
TI  - Trends in permanent pacemaker implantation in the United States from 1993 to
      2009: increasing complexity of patients and procedures.
AB  - OBJECTIVES: This study sought to define contemporary trends in permanent
      pacemaker use by analyzing a large national database. BACKGROUND: The Medicare
      National Coverage Determination for permanent pacemaker, which emphasized single
      chamber pacing, has not changed significantly since 1985. We sought to define
      contemporary trends in permanent pacemaker use by analyzing a large national
      database. METHODS: We queried the Nationwide Inpatient Sample to identify
      permanent pacemaker implants between 1993 and 2009 using the International
      Classification of Diseases-Ninth Revision-Clinical Modification procedure codes
      for dual-chamber (DDD), single-ventricular (VVI), single-atrial (AAI), or
      biventricular (BiV) devices. Annual permanent pacemaker implantation rates and
      patient demographics were analyzed. RESULTS: Between 1993 and 2009, 2.9 million
      patients received permanent pacemakers in the United States. Overall use
      increased by 55.6%. By 2009, DDD use increased from 62% to 82% (p < 0.001),
      whereas single-chamber ventricular pacemaker use fell from 36% to 14% (p = 0.01).
      Use of DDD devices was higher in urban, nonteaching hospitals (79%) compared with
      urban teaching hospitals (76%) and rural hospitals (72%). Patients with private
      insurance (83%) more commonly received DDD devices than Medicaid (79%) or
      Medicare (75%) recipients (p < 0.001). Patient age and Charlson comorbidity index
      increased over time. Hospital charges ($2011) increased 45.3%, driven by the
      increased cost of DDD devices. CONCLUSIONS: There is a steady growth in the use
      of permanent pacemakers in the United States. Although DDD device use is
      increasing, whereas single-chamber ventricular pacemaker use is decreasing.
      Patients are becoming older and have more medical comorbidities. These trends
      have important health care policy implications.

PMID- 22999728
TI  - CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study
      of 951 patients referred for elective coronary angiography.
AB  - OBJECTIVES: The aim of this study was to analyze the yet ill-defined relationship
      of distinct human monocyte subsets with cardiovascular outcomes in a broad
      patient population at cardiovascular risk. BACKGROUND: Monocytes, the most
      abundant immune cell type found in atherosclerotic plaques, are crucial promoters
      of atherogenesis. Three distinct human monocyte subsets exist: classical
      CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes.
      Immunomodulation of distinct monocyte subsets has recently been discussed as a
      new therapeutic avenue in atherosclerosis. METHODS: Cardiovascular events in 951
      subjects referred for elective coronary angiography were prospectively analyzed.
      Monocyte subset analysis was performed using flow cytometry, blinded to patients'
      clinical characteristics, and patients were categorized according to quartiles of
      total monocyte and monocyte subset counts. The primary endpoint was defined a
      priori as the first occurrence of cardiovascular death, acute myocardial
      infarction, or nonhemorrhagic stroke. Endpoint adjudication was done blinded to
      monocyte subset distribution. RESULTS: During a mean follow-up period of 2.6 +/-
      1.0 years, 93 patients experienced the primary endpoint. In univariate Kaplan
      Meier analysis, counts of total (p = 0.010), classical CD14++CD16- (p = 0.024),
      and intermediate CD14++CD16+ (p < 0.001) monocytes predicted the primary
      endpoint, whereas nonclassical monocytes did not (p = 0.158). After full
      adjustment for confounders, CD14++CD16+ monocytes remained the only monocyte
      subset independently related to cardiovascular events (fourth vs. first quartile:
      hazard ratio: 3.019; 95% confidence interval: 1.315 to 6.928; p = 0.009).
      CONCLUSIONS: CD14++CD16+ monocytes independently predicted cardiovascular events
      in subjects referred for elective coronary angiography. Future studies will be
      needed to elucidate whether CD14++CD16+ monocytes may become a target cell
      population for new therapeutic strategies in atherosclerosis.

PMID- 22999730
TI  - 10-year exercise training in chronic heart failure: a randomized controlled
      trial.
AB  - OBJECTIVES: This study investigated the effect of a very long-term exercise
      training program is not known in chronic heart failure (CHF) patients.
      BACKGROUND: We previously showed that long-term moderate exercise training (ET)
      improves functional capacity and quality of life in New York Heart Association
      class II and III CHF patients. METHODS: We studied 123 patients with CHF whose
      condition was stable over the previous 3 months. After randomization, a trained
      group (T group, n = 63) underwent a supervised ET at 60% of peak oxygen
      consumption (Vo(2)), 2 times weekly for 10 years, whereas a nontrained group (NT
      group, n = 60) did not exercise formally. The ET program was supervised and
      performed mostly at a coronary club with periodic control sessions twice yearly
      at the hospital's gym. RESULTS: In the T group, peak Vo(2) was more than 60% of
      age- and gender-predicted maximum Vo(2) each year during the 10-year study (p <
      0.05 vs. the NT group). In NT patients, peak Vo(2) decreased progressively with
      an average of 52 +/- 8% of maximum Vo(2) predicted. Ventilation relative to
      carbon dioxide output (VE/Vco(2)) slope was significantly lower (35 +/- 9) in T
      patients versus NT patients (42 +/- 11, p < 0.01). Quality-of-life score was
      significantly better in the T group versus the NT group (43 +/- 12 vs. 58 +/- 14,
      p < 0.05). During the 10-year study, T patients had a significant lower rate of
      hospital readmission (hazard ratio: 0.64, p < 0.001) and cardiac mortality
      (hazard ratio: 0.68, p < 0.001) than controls. Multivariate analysis selected
      peak Vo(2) and resting heart rate as independent predictors of events.
      CONCLUSIONS: Moderate supervised ET performed twice weekly for 10 years maintains
      functional capacity of more than 60% of maximum Vo(2) and confers a sustained
      improvement in quality of life compared with NT patients. These sustained
      improvements are associated with reduction in major cardiovascular events,
      including hospitalizations for CHF and cardiac mortality.

PMID- 22999729
TI  - Mortality and cardiovascular events are best predicted by low central/peripheral
      pulse pressure amplification but not by high blood pressure levels in elderly
      nursing home subjects: the PARTAGE (Predictive Values of Blood Pressure and
      Arterial Stiffness in Institutionalized Very Aged Population) study.
AB  - OBJECTIVES: The aim of the longitudinal PARTAGE study was to determine the
      predictive value of blood pressure (BP) and pulse pressure amplification, a
      marker of arterial function, for overall mortality (primary endpoint) and major
      cardiovascular (CV) events, in subjects older than 80 years of age living in a
      nursing home. BACKGROUND: Assessment of pulse indexes may be important in the
      evaluation of the CV risk in very elderly frail subjects. METHODS: A total of
      1,126 subjects (874 women) who were living in French and Italian nursing homes
      were enrolled (mean age, 88 +/- 5 years). Central (carotid) to peripheral
      (brachial) pulse pressure amplification (PPA) was calculated with the help of an
      arterial tonometer. Clinical and 3-day self-measurements of BP were conducted.
      RESULTS: During the 2-year follow-up, 247 subjects died, and 228 experienced
      major CV events. The PPA was a predictor of total mortality and major CV events
      in this population. A 10% increase in PPA was associated with a 24% (p < 0.0003)
      decrease in total mortality and a 17% (p < 0.01) decrease in major CV events.
      Systolic BP, diastolic BP, or pulse pressure were either not associated or
      inversely correlated with total mortality and major CV events. CONCLUSIONS: In
      very elderly individuals living in nursing homes, low PPA from central to
      peripheral arteries strongly predicts mortality and adverse effects. Assessment
      of this parameter could help in risk estimation and improve diagnostic and
      therapeutic strategies in very old, polymedicated persons. In contrast, high BP
      is not associated with higher risk of mortality or major CV events in this
      population. (Predictive Values of Blood Pressure and Arterial Stiffness in
      Institutionalized Very Aged Population [PARTAGE]; NCT00901355).

PMID- 22999731
TI  - Taking the cells out of cell therapy.

PMID- 22999732
TI  - The problem with asymptomatic cerebral embolic complications in vascular
      procedures: what if they are not asymptomatic?
AB  - Cerebral embolic events related to carotid and cardiac disease have been known
      for decades. Recently, cerebral embolic events have become a focus of clinical
      importance as complications of vascular procedures. Further, the development of
      new technologies and procedures has increased the overall clinical significance.
      Although the relative safety of these procedures is usually defined by acute
      stroke risk, it is also becoming clear that far more subclinical events are
      occurring. Recent reports provided substantial evidence of memory loss, cognitive
      decline, and dementia related to these so-called silent infarcts. Literature
      reports of magnetic resonance imaging events lead to an estimate of as many as
      600,000 patients with new brain injury each year in the United States alone.
      Given the magnitude of the numbers involved, the impact of accelerated cognitive
      loss and premature senescence in a vulnerable at-risk population could well be
      significant.

PMID- 22999733
TI  - Pre-procedural risk quantification for carotid stenting using the CAS score: a
      report from the NCDR CARE Registry.
AB  - OBJECTIVES: We developed and internally validated a risk score to predict in
      hospital stroke or death after carotid artery stenting (CAS). BACKGROUND: A tool
      that accurately assesses CAS risk could aid clinical decision making and improve
      patient selection. METHODS: Patients undergoing CAS without acute evolving stroke
      from April 2005 through June 2011 as part of the NCDR Carotid Artery
      Revascularization and Endarterectomy (CARE) Registry were included. In-hospital
      stroke or death was modeled using logistic regression with 35 candidate
      variables. Internal validation was achieved with bootstrapping, and model
      discrimination and calibration were assessed. RESULTS: A total of 271 (2.4%)
      primary endpoint events occurred during 11,122 procedures. Independent predictors
      of stroke or death included impending major surgery, previous stroke, age,
      symptomatic lesion, atrial fibrillation, and absence of previous ipsilateral
      carotid endarterectomy. The model was well calibrated with moderate
      discriminatory ability (C-statistic: 0.71) overall, and within symptomatic (C
      statistic: 0.68) and asymptomatic (C-statistic: 0.72) subgroups. The inclusion of
      available angiographic variables did not improve model performance (C-statistic:
      0.72, integrated discrimination improvement 0.001; p = 0.21). The NCDR CAS score
      was developed to support prospective risk quantification. CONCLUSIONS: The NCDR
      CAS score, comprising 6 clinical variables, predicts in-hospital S/D after CAS.
      This tool may be useful to assist clinicians in evaluating optimal management,
      share more accurate pre-procedural risks with patients, and improve patient
      selection for CAS.

PMID- 22999734
TI  - Should we indeed measure carotid intima-media thickness for improving prediction
      of cardiovascular events after IMPROVE?

PMID- 22999735
TI  - Antiarrhythmic potential of mesenchymal stem cell is modulated by hypoxic
      environment.
AB  - OBJECTIVES: The purpose of this study was to evaluate the antiarrhythmic
      potential of mesenchymal stem cells (MSC) under a different environment.
      BACKGROUND: Little is known about how environmental status affects antiarrhythmic
      potential of MSCs. METHODS: To investigate the effect of paracrine factors
      secreted from MSCs under different circumstances on arrhythmogenicity in rats
      with myocardial infarction, we injected paracrine media (PM) secreted under
      hypoxic, normoxic conditions (hypoxic PM and normoxic PM), and MSC into the
      border zone of infarcted myocardium in rats. RESULTS: We found that the injection
      of hypoxic PM, but not normoxic PM, markedly restored conduction velocities,
      suppressed focal activity, and prevented sudden arrhythmic deaths in rats.
      Underlying this electrophysiological alteration was a decrease in fibrosis,
      restoration of connexin 43, alleviation of Ca(2+) overload, and recovery of
      Ca(2+)-regulatory ion channels and proteins, all of which is supported by
      proteomic data showing that several paracrine factors including basic fibroblast
      growth factor, insulinlike growth factor 1, hepatocyte growth factor, and EF-hand
      domain-containing 2 are potential mediators. When compared with PM, MSC injection
      did not reduce or prevent arrhythmogenicity, suggesting that the antiarrhythmic
      or proarrhythmic potential of MSC is mainly dependent on paracrine factors.
      CONCLUSIONS: A hypoxic or normoxic environment surrounding MSC affects the type
      and properties of the growth factors or cytokines, and these secreted molecules
      determine the characteristics of the electro-anatomical substrate of the
      surrounding myocardium.

PMID- 22999736
TI  - Self-regulation of brain oscillations as a treatment for aberrant brain
      connections in children with autism.
AB  - Autism is a highly varied developmental disorder typically characterized by
      deficits in reciprocal social interaction, difficulties with verbal and nonverbal
      communication, and restricted interests and repetitive behaviors. Although a wide
      range of behavioral, pharmacological, and alternative medicine strategies have
      been reported to ameliorate specific symptoms for some individuals, there is at
      present no cure for the condition. Nonetheless, among the many incompatible
      observations about aspects of the development, anatomy, and functionality of the
      autistic brain, it is widely agreed that it is characterized by widespread
      aberrant connectivity. Such disordered connectivity, be it increased, decreased,
      or otherwise compromised, may complicate healthy synchronization and
      communication among and within different neural circuits, thereby producing
      abnormal processing of sensory inputs necessary for normal social life. It is
      widely accepted that the innate properties of brain electrical activity produce
      pacemaker elements and linked networks that oscillate synchronously or
      asynchronously, likely reflecting a type of functional connectivity. Using phase
      coherence in multiple frequency EEG bands as a measure of functional
      connectivity, studies have shown evidence for both global hypoconnectivity and
      local hyperconnectivity in individuals with ASD. However, the nature of the
      brain's experience-dependent structural plasticity suggests that these abnormal
      patterns may be reversed with the proper type of treatment. Indeed, neurofeedback
      (NF) training, an intervention based on operant conditioning that results in self
      regulation of brain electrical oscillations, has shown promise in addressing
      marked abnormalities in functional and structural connectivity. It is
      hypothesized that neurofeedback produces positive behavioral changes in ASD
      children by normalizing the aberrant connections within and between neural
      circuits. NF exploits the brain's plasticity to normalize aberrant connectivity
      patterns apparent in the autistic brain. By grounding this training in known
      anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms)
      of autism, NF training holds promise to support current treatments for this
      complex disorder. The proposed hypothesis specifically states that neurofeedback
      induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of
      cortical activation, should induce neuroplastic changes and lead to normalization
      in relevant mirroring networks that have been associated with higher-order social
      cognition.

PMID- 22999737
TI  - The cerebello-hypothalamic-pituitary-adrenal axis dysregulation hypothesis in
      depressive disorder.
AB  - Depressive disorder can be viewed as an adaptive defense mechanism in response to
      excessive stress that has gone awry. The hypothalamic-pituitary-adrenal (HPA)
      axis is an important node in the brain's stress circuit and suggested to play a
      role in several subtypes of depression. While the hippocampus, amygdala and
      prefrontal cortex are considered important regions implicated in stress
      regulation and depressive disorder, the existence of reciprocal monosynaptic
      cerebello-hypothalamic connections and the presence of dense glucocorticoid
      binding sites point towards the view that the cerebellum plays a functional role
      in the regulation of HPA-axis as well. The present hypothesis may further
      contribute to contemporary neurobiological views on stress regulation and
      depressive disorder, and may offer a potential biological basis for developing
      novel neurosomatic treatment protocols.

PMID- 22999738
TI  - Intelligent bioengineering in vitiligo treatment: transdermal protein
      transduction of melanocyte-lineage-specific genes.
AB  - Vitiligo is a common, incurable skin disease with a prevalence of about 1%.
      Although many vitiligo therapies are available in clinics, there is almost no one
      method that causes significant improvement in all vitiligo patients. Some have
      hypothesized that melanocyte dysfunction or deficiency underlies the loss of skin
      pigmentation observed in vitiligo. The autoimmune-mediated apoptosis of
      melanocytes might be an important part of the etiology of vitiligo, which
      prevents the formation of melanocytes in the skin. Here we propose a novel
      hypothesis for vitiligo treatment using in situ melanocyte regeneration induced
      by melanocyte-lineage-specific genes (MLSGs). This may serve as an intelligent
      bioengineering prototype. The hypothesis is based on the fact that MLSGs regulate
      melanocyte differentiation through epigenetic reprogramming, which includes
      microphthalmia-associated transcription factor (MITF), paired box 3 (PAX3), and
      Notch signaling. MITF directs the terminal differentiation of melanocytes, and
      PAX3 helps to establish the properties of the melanocyte stem cells. Notch
      signaling promotes adult stem cell proliferation and self-renewal. This process
      could be mimicked by Notch intracellular domain (NICD). MLSGs could also
      stimulate anti-apoptotic gene expression. Recent improvements in relevant
      biotechniques allow the transdermal delivery of MLSG proteins into the patient,
      where they enter cells through protein transduction. This process may promote
      melanocyte regeneration in situ with little impact on the hair follicular cycle
      or on carcinogenesis. This simple and efficient treatment may have significant
      impact on the treatment of vitiligo patients.

PMID- 22999739
TI  - Validation of a DNA mixture statistics tool incorporating allelic drop-out and
      drop-in.
AB  - DNA mixture analysis is a current topic of discussion in the forensics
      literature. Of particular interest is how to approach mixtures where allelic drop
      out and/or drop-in may have occurred. The Office of Chief Medical Examiner (OCME)
      of The City of New York has developed and validated the Forensic Statistical Tool
      (FST), a software tool for likelihood ratio analysis of forensic DNA samples,
      allowing for allelic drop-out and drop-in. FST can be used for single source
      samples and for mixtures of DNA from two or three contributors, with or without
      known contributors. Drop-out and drop-in probabilities were estimated empirically
      through analysis of over 2000 amplifications of more than 700 mixtures and single
      source samples. Drop-out rates used by FST are a function of the Identifiler((r))
      locus, the quantity of template DNA amplified, the number of amplification
      cycles, the number of contributors to the sample, and the approximate mixture
      ratio (either unequal or approximately equal). Drop-out rates were estimated
      separately for heterozygous and homozygous genotypes. Drop-in rates used by FST
      are a function of number of amplification cycles only. FST was validated using
      454 mock evidence samples generated from DNA mixtures and from items handled by
      one to four persons. For each sample, likelihood ratios (LRs) were computed for
      each true contributor and for each profile in a database of over 1200 non
      contributors. A wide range of LRs for true contributors was obtained, as true
      contributors' alleles may be labeled at some or all of the tested loci. However,
      the LRs were consistent with OCME's qualitative assessments of the results. The
      second set of data was used to evaluate FST LR results when the test sample in
      the prosecution hypothesis of the LR is not a contributor to the mixture. With
      this validation, we demonstrate that LRs generated using FST are consistent with,
      but more informative than, OCME's qualitative sample assessments and that LRs for
      non-contributors are appropriately assigned.

PMID- 22999740
TI  - Meticillin-resistant Staphylococcus aureus screening in Wales: survey of
      practices in adult critical care units in Welsh hospitals.
AB  - Screening for meticillin-resistant Staphylococcus aureus (MRSA) carriage in
      critical care units remains a controversial issue. This cross-sectional study
      reviewed the MRSA screening policies in adult critical care units in Welsh
      hospitals. Data were collected by structured questionnaires. The study showed a
      degree of variability in practice from universal screening to no screening at
      all. It is recommended that local MRSA policies should be reviewed, bearing in
      mind the local prevalence of colonization and infection; and compliance with
      basic infection control strategies should not only be directed at MRSA infection,
      but also at other healthcare-associated infections.

PMID- 22999742
TI  - The seven sins of fluorescence measurements.

PMID- 22999741
TI  - Reduction of Na+, K+-ATPase activity and expression in cerebral cortex of
      glutaryl-CoA dehydrogenase deficient mice: a possible mechanism for brain injury
      in glutaric aciduria type I.
AB  - Mitochondrial dysfunction has been proposed to play an important role in the
      neuropathology of glutaric acidemia type I (GA I). However, the relevance of
      bioenergetics disruption and the exact mechanisms responsible for the cortical
      leukodystrophy and the striatum degeneration presented by GA I patients are not
      yet fully understood. Therefore, in the present work we measured the respiratory
      chain complexes activities I-IV, mitochondrial respiratory parameters state 3,
      state 4, the respiratory control ratio and dinitrophenol (DNP)-stimulated
      respiration (uncoupled state), as well as the activities of alpha-ketoglutarate
      dehydrogenase (alpha-KGDH), creatine kinase (CK) and Na+, K+-ATPase in cerebral
      cortex, striatum and hippocampus from 30-day-old Gcdh-/- and wild type (WT) mice
      fed with a normal or a high Lys (4.7%) diet. When a baseline (0.9% Lys) diet was
      given, we verified mild alterations of the activities of some respiratory chain
      complexes in cerebral cortex and hippocampus, but not in striatum from Gcdh-/-
      mice as compared to WT animals. Furthermore, the mitochondrial respiratory
      parameters and the activities of alpha-KGDH and CK were not modified in all brain
      structures from Gcdh-/- mice. In contrast, we found a significant reduction of
      Na(+), K(+)-ATPase activity associated with a lower degree of its expression in
      cerebral cortex from Gcdh-/- mice. Furthermore, a high Lys (4.7%) diet did not
      accentuate the biochemical alterations observed in Gcdh-/- mice fed with a normal
      diet. Since Na(+), K(+)-ATPase activity is required for cell volume regulation
      and to maintain the membrane potential necessary for a normal neurotransmission,
      it is presumed that reduction of this enzyme activity may represent a potential
      underlying mechanism involved in the brain swelling and cortical abnormalities
      (cortical atrophy with leukodystrophy) observed in patients affected by GA I.

PMID- 22999743
TI  - The hemi-stenting technique in lymphaticovenular anastomosis.

PMID- 22999745
TI  - Combining hepatic arterial infusion and systemic therapy: radiologic versus
      surgical approaches.

PMID- 22999747
TI  - Treatment of recurrent hepatocellular carcinoma: reinforcing the role of the
      interventional oncologist.

PMID- 22999746
TI  - Computed tomography follow-up for the detection of hepatocellular carcinoma
      recurrence after initial radiofrequency ablation: a single-center experience.
AB  - PURPOSE: Recurrence of hepatocellular carcinoma (HCC) is very common even after
      curative resection or ablation. This retrospective study compared the radiologic
      features of recurrent HCC seen by computed tomography (CT) to evaluate our
      empirical protocol of CT surveillance using 4-month intervals. MATERIALS AND
      METHODS: A total of 113 patients who were diagnosed with a first HCC recurrence
      after radiofrequency (RF) ablation between January 2005 and December 2006 were
      enrolled at a single center. Definite HCC was defined as hyperattenuation in the
      arterial phase with washout in the portal venous phase, and a diagnosis of naive
      and recurrent HCC was based on dynamic CT findings. Recurrent nodules were
      classified according to the enhancement patterns of previous CT images. The
      treatment modality for recurrent HCC and survival were evaluated. RESULTS: One
      hundred seventy-seven nodules were diagnosed as recurrent HCC: 31 (17.5%) had
      already been diagnosed on previous CT images as typical HCC, 72 (40.6%) had
      arterial hypervascularity without washout in the portal venous phase, 21 (11.9%)
      showed portal venous phase washout without arterial hypervascularity, and no
      lesions were noted in the remaining 49 (27.7%). Tumor size at recurrence was
      smaller than 2 cm in diameter in 98 (86.7%) cases. One hundred four patients were
      treated for recurrent HCC with RF ablation. The 5-year survival rate after
      recurrence was 49.8%. There was no significant difference in survival among
      groups divided by the enhancement pattern on the previous CT examination.
      CONCLUSIONS: Dynamic CT in 4-month intervals is an acceptable recurrence
      monitoring strategy because it detects most recurrent nodules at a stage at which
      RF ablation is still feasible.

PMID- 22999748
TI  - Safety and feasibility of same-day discharge of patients with unresectable
      hepatocellular carcinoma treated with doxorubicin drug-eluting bead transcatheter
      chemoembolization.
AB  - PURPOSE: The aim of this study was to investigate the safety and feasibility of
      same-day discharge of patients with unresectable hepatocellular carcinoma (HCC)
      after doxorubicin drug-eluting bead (DEB) transarterial chemoembolization and to
      elucidate the factors predisposing to overnight admission. MATERIALS AND METHODS:
      Consecutive patients with unresectable HCC who underwent superselective 100-300
      MUm DEB transarterial chemoembolization were included. The parameters of same-day
      therapy (group A) were compared with those of patients admitted overnight (group
      B). A chi2 test and a t test were used to compare categorical and continuous
      variables accordingly. RESULTS: Seventy-six patients (mean, 61 y) received 110
      DEB transarterial chemoembolization treatments over an 8-month study period. In
      84.5% (93/110) of DEB transarterial chemoembolization procedures, the patients
      were discharged on the same day (group A). The causes of hospitalization included
      the worsening of comorbidities in 41.1% (7/17), pain control in 29.4% (5/17), and
      groin and closure device-related complications in 29.4% (5/17) of patients. The
      mean Charlson comorbidity scores in groups A and B were 6.96 (standard deviation
      [SD] +/- 1.98) and 8.47 (SD +/- 2.18) (P = .0005), respectively. All of the
      patients in group B had Barcelona Clinic Liver Cancer (BCLC) stages C and D HCC
      (P = .024). There were no Common Terminology Criteria for Adverse Events (CTCAE)
      grade III or worse adverse events (AEs). There was no mortality or emergency
      visits within 30 days of discharge. CONCLUSIONS: Same-day discharge after
      superselective DEB transarterial chemoembolization for unresectable HCC is safe
      and feasible. BCLC C or D stage of disease, a higher Charlson comorbidity score,
      and groin or closure device complications are correlated with a greater
      likelihood for overnight admission.

PMID- 22999749
TI  - Role of venoplasty for treatment of multiple sclerosis: value of open-label
      studies and surrogate treatment outcomes.

PMID- 22999750
TI  - Ever done or moving on?

PMID- 22999751
TI  - Case report: an unusual combined retrograde and antegrade transpedal subintimal
      recanalization of the infrainguinal arteries.
AB  - Retrograde or combined retrograde and antegrade recanalization should be
      considered when antegrade recanalization has failed in selected patients with
      critical limb ischemia (CLI). Retrograde recanalization is typically attempted
      through a patent segment of the popliteal artery or an infrapopliteal artery. The
      challenge arises, however, when there are no patent popliteal or infrapopliteal
      arteries suitable for retrograde access.

PMID- 22999752
TI  - Endovascular treatment of a congenital thoracic aortic aneurysm in a premature
      newborn.
AB  - Congenital aortic aneurysms are a rare, life-threatening disorder that present
      complex treatment challenges. The authors describe a congenital thoracic aortic
      aneurysm treated by endovascular means with stent-assisted coil deployment.
      Because of rapid in utero aneurysm growth and cardiac dysfunction, a 2.6-kg male
      was delivered expeditiously by Cesarean section at 35(2)/(7) weeks' gestation. On
      day of life 1, bilateral femoral arterial access was used to deliver a balloon
      expandable stent across the wide-necked aneurysm. Microcoil embolization of the
      aneurysm via a prepositioned microcatheter was then performed. The child had an
      uncomplicated hospital course and is asymptomatic 5 months later, with complete
      aneurysm thrombosis.

PMID- 22999753
TI  - Innovative solutions: an axiom of interventional radiology.

PMID- 22999754
TI  - Anatomic features and retrograde transvenous obliteration of duodenal varices
      associated with mesocaval collateral pathway.
AB  - PURPOSE: To evaluate techniques and efficacy of retrograde transvenous
      obliteration for the treatment of duodenal varices associated with mesocaval
      collateral pathway. MATERIALS AND METHODS: Six consecutive cases of large/growing
      or ruptured duodenal varices treated by retrograde transvenous obliteration were
      retrospectively reviewed. Selective balloon-occluded retrograde transvenous
      obliteration (B-RTO) with 5% ethanolamine oleate (EO) was performed in all cases.
      When EO could not be sufficiently stagnated in the varices,
      additional/alternative techniques were performed, including coil embolization of
      afferent vein or intravariceal injection of n-butyl-2-cyanoacrylate (NBCA).
      Clinical findings, anatomic features of duodenal varices, obliteration
      techniques, complications, posttherapeutic computed tomography (CT) findings, and
      follow-up endoscopic findings were investigated. RESULTS: All duodenal varices
      were located at the second/third junction of the duodenum and were fed by single
      (n = 1) or multiple (n = 5) pancreaticoduodenal veins. One varix fed by a single
      afferent vein was successfully treated by simple selective B-RTO technique alone.
      The other five cases required coil embolization of afferent vein (n = 1) or
      intravariceal injection of NBCA (n = 4) because sclerosant was not sufficiently
      stagnated in the varices. CT 1 week after the procedure showed complete occlusion
      of the varices in all cases. A duodenal ulcer at the variceal site developed in
      one patient and was successfully treated by medication. Follow-up endoscopy
      showed disappearance of varices in all cases, and no recurrence was observed
      during follow-up. CONCLUSIONS: Retrograde transvenous obliteration is an
      effective technique for the treatment of duodenal varices. However,
      additional/alternative techniques are required for successful treatment because
      of the complex anatomic features of duodenal varices.

PMID- 22999756
TI  - Biliary stricture dilation: are the unknowns known?

PMID- 22999755
TI  - Long-term results of percutaneous biliary balloon dilation treatment for benign
      hepaticojejunostomy strictures: are repeated balloon dilations necessary?
AB  - PURPOSE: To determine the safety, efficacy, and long-term results of percutaneous
      biliary balloon dilation (PBBD) of benign hepaticojejunostomy strictures and
      evaluate the necessity of repeated PBBD in this setting. MATERIALS AND METHODS:
      PBBD was performed after traversing hepaticojejunostomy strictures in 89 patients
      (40 male, 49 female; age range, 19-84 y; mean age +/- SD, 54.5 y +/- 14.0), who
      were divided into three groups: group I (one satisfactory initial PBBD; n = 41),
      group II (two or more PBBDs with satisfactory initial PBBD; n = 33), and group
      III (two or more PBBDs without satisfactory PBBD; n = 15). Groups I and II were
      randomized. The primary outcome measure was the absence of clinical biliary
      obstruction symptoms at 24 months. Secondary outcome measures included technical
      and clinical success, primary and secondary patency, major complications, and
      mortality. Categoric variables were compared between groups I and II. RESULTS:
      Procedure-related mortality and major morbidity rates were 0% and 5.6%,
      respectively. Mean primary and secondary patency durations were 45.3 months +/-
      2.2 and 71.3 months +/- 15.4, respectively. The follow-up period was 36.4 months
      +/- 15.1. The primary outcome measure was achieved in 73% of patients. Technical
      and clinical success rates (secondary outcome measures) were 97.8% and 84.3%,
      respectively. Repeated PBBD procedures were not satisfactory in 16.9% of
      patients. No significant differences in categoric variables were observed between
      groups I and II. CONCLUSIONS: PBBD of benign hepaticojejunostomy strictures is a
      safe and effective procedure. Repeated PBBD is not required when the first
      procedure is successful.

PMID- 22999757
TI  - Evaluation of the Orcamp hybrid high-fidelity environment for simulation
      training.

PMID- 22999758
TI  - Malignant inferior vena cava syndrome and congestive hepatic failure treated by
      venous stent placement.
AB  - A 65-year-old woman with liver metastases from colon cancer and tumor thrombus
      extending from the right hepatic vein (HV) to the right atrium (RA) presented
      with marked lower-extremity edema and massive ascites. Computed tomography showed
      tumor thrombus completely occluding the inferior vena cava (IVC) and HV ostia.
      Recanalization of the IVC and HVs was performed. Metallic stents were placed in
      tandem from the superior vena cava to the IVC through the RA, and additional
      metallic stents were placed in the left HV. The patient's symptoms were relieved,
      and there was no recurrence of these symptoms for 19.5 months until death.

PMID- 22999759
TI  - Endovascular stenting and stent-graft repair of a hemorrhagic superior mesenteric
      artery pseudoaneurysm and dissection associated with pancreaticoduodenectomy.
AB  - This report presents a 73-year-old woman with intraperitoneal bleeding from a
      superior mesenteric artery (SMA) pseudoaneurysm and dissection after
      pancreaticoduodenectomy (PD). A self-expanding bare metal stent was placed in the
      distal SMA across the area of dissection, and a stent-graft was subsequently
      placed across the pseudoaneurysm emerging from the proximal site by overlapping
      the bare stent, resulting in complete exclusion of the pseudoaneurysm and control
      of the dissection. Bleeding was controlled after the endovascular procedure. The
      combination of endovascular stenting and stent-graft repair is feasible and
      useful in comorbid cases of SMA pseudoaneurysm and dissection.

PMID- 22999760
TI  - CT angiography of abdominal aortic aneurysms: not everything that is not white is
      thrombus.

PMID- 22999761
TI  - Balloon occlusion of subintimal tract to assist distal luminal reentry into
      popliteal artery.

PMID- 22999762
TI  - Successful treatment of intramuscular venous malformation with image-guided
      radiofrequency ablation.

PMID- 22999763
TI  - Reversible cerebral vasoconstriction syndrome occurring after uterine artery
      embolization for uterine fibroids.

PMID- 22999764
TI  - Putative role of an ABC transporter in Fonsecaea pedrosoi multidrug resistance.
AB  - Fonsecaea pedrosoi, a dematiaceous fungus, is the main agent responsible for
      chromoblastomycosis, a chronic and progressive mycosis of the skin and
      subcutaneous tissues. This disease can cause different types of lesions depending
      on the immune status of the host. Its treatment is complicated by the toxicity of
      available antifungal agents as well as drug resistance. In this work, an ATP
      binding cassette (ABC) transporter in this fungus was characterised, with the
      degree of expression related to the drug resistance of two strains (a patient
      isolated strain and a laboratory strain). A 150 kDa protein was detected by
      western blotting. The ATPase activity of membrane preparations was also
      evaluated. The F. pedrosoi transporter appears to behave like Pdr5p, a well
      studied multidrug resistance transporter in Saccharomyces cerevisiae with the
      ability to hydrolyse different triphosphate nucleotides, as well as its response
      to classical inhibitors tested. Finally, a reverse transcription polymerase chain
      reaction (RT-PCR) approach was used and a 400 bp product was detected,
      corresponding to the highly conserved ATP-binding domain of ABC transporters. We
      suggest that an ABC transporter must be involved in F. pedrosoi multidrug
      resistance, and a complete understanding of this protein could bring an important
      contribution to antifungal treatment of this disease.

PMID- 22999765
TI  - Epigallocatechin gallate as a modulator of Campylobacter resistance to macrolide
      antibiotics.
AB  - Comprehensive therapeutic use of macrolides in humans and animals is important in
      the selection of macrolide-resistant Campylobacter isolates. This study shows
      high co-resistance to erythromycin, azithromycin, clarithromycin, dirithromycin
      and tylosin, with contributions from the 23S rRNA gene and drug efflux systems.
      The CmeABC efflux pump plays an important role in reduced macrolide
      susceptibility, accompanied by contributions from the CmeDEF efflux pump and
      potentially a third efflux pump. To improve clinical performance of licensed
      antibiotics and chemotherapeutic agents, it is important to understand the
      factors in Campylobacter that affect susceptibility to macrolide antibiotics.
      Using mutants that lack the functional genes coding for the CmeB and CmeF efflux
      pump proteins and the CmeR transcriptional repressor, we show that these efflux
      pumps are potential targets for the development of therapeutic strategies that
      use a combination of a macrolide with an efflux pump inhibitor (EPI) to restore
      macrolide efficacy. The natural phenolic compound epigallocatechin gallate (EGCG)
      has good modulatory activity over the extrusion across the outer membrane of the
      macrolides tested, both in sensitive and resistant Campylobacter isolates.
      Comparing EGCG with known chemical EPIs, correlations in the effects on the
      particular macrolide antibiotics were seen. EGCG modifies Campylobacter multidrug
      efflux systems and thus could have an impact on restoring macrolide efficacy in
      resistant strains.

PMID- 22999766
TI  - Risk factors for anti-MRSA drug resistance.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA)-related infections have
      recently been spreading and are difficult to control, partly because affected
      patients are frequently in a poor condition. This study retrospectively
      investigated recent MRSA-related infections focusing on the relationship between
      clinical risk factors and anti-MRSA drug resistance. The patients with MRSA
      related infections in Kobe University Hospital (Kobe, Japan) in 2009 were
      enrolled in the study. The relationships between various clinical risk factors as
      well as MRSA bacterial DNA concentration with minimum inhibitory concentrations
      (MICs) of anti-MRSA drugs were examined. In total, 44 patients were enrolled in
      the study and MRSA was isolated from blood (23 patients), urine (12 patients) and
      nasal secretions (9 patients). There was only one resistant strain to linezolid
      (LZD) among the anti-MRSA drugs tested, and this strain was considered
      staphylococcal cassette chromosome mec (SCCmec) type IIa from phage open-reading
      frame typing analyses. Statistical analyses showed that MRSA bacterial DNA
      concentration, cancer and use of a respirator, respectively, had a significant
      relationship with the MICs of LZD (P=0.0058) and arbekacin (ABK) (P=0.0003), of
      quinupristin/dalfopristin (Q/D) (P=0.0500) and ABK (P=0.0133), and of Q/D
      (P=0.0198) and vancomycin (P=0.0036). In conclusion, bacterial DNA concentration,
      cancer and use of a respirator were found to be significant risk factors for
      lower susceptibilities to anti-MRSA drugs; one strain was resistant to LZD. We
      suggest that further investigation and surveillance for MRSA-related infection
      are necessary for preventing the spread of MRSA-related infections.

PMID- 22999767
TI  - Antibiotic resistance amongst healthcare-associated pathogens in China.
AB  - The People's Republic of China, commonly known as China, comprises approximately
      one-fifth of the world's population. Because of the expanding size and density of
      its population and the frequent interaction of people with animals, China is a
      hotspot for the emergence and spread of new microbial threats and is a major
      contributor to the worldwide infectious disease burden. In recent years, the
      emergence and rapid spread of severe acute respiratory syndrome (SARS) generated
      considerable interest in the Chinese healthcare system and its infection control
      and prevention measures. This review examines antibiotic misuse and the status of
      antibiotic resistance in the Chinese healthcare system. China has high rates of
      antibiotic resistance driven by misuse of these agents in a healthcare system
      that provides strong incentives for overprescribing and in a country where self
      medication is common. Tuberculosis remains a serious problem in China, with a
      high prevalence of multidrug-resistant and extensively drug-resistant strains.
      Drug resistance amongst nosocomial bacteria has been on a rapid upward trend with
      a strong inclination towards multidrug resistance. There is a need for effective
      infection prevention and control measures and strict use of antibiotics in China
      to control the rise and spread of antibiotic resistance in the country.

PMID- 22999768
TI  - Prevalence of quinolone resistance and mutations in the topoisomerase genes in
      Salmonella enterica serotype Enteritidis isolates from Serbia.
AB  - The prevalence of quinolone resistance was studied in Salmonella enterica
      serotype Enteritidis isolates collected during 2005-2010 in Southern Backa
      County, Serbia. A total of 878 clinical isolates were examined, among which 19
      (2.2%) nalidixic acid (NAL)-resistant S. Enteritidis were detected by selection
      on agar plates containing 64 mg/L NAL. Antimicrobial susceptibility of the
      isolates was tested by the agar dilution method. According to Clinical and
      Laboratory Standards Institute (CLSI) breakpoints, ciprofloxacin (CIP) resistance
      was not present in the strains. Multiple drug resistance was rare, and resistance
      to NAL was most often present as a single resistance property. All but one NAL
      resistant S. Enteritidis showed reduced susceptibility to CIP [i.e. minimum
      inhibitory concentration (MIC)>=0.125 mg/L]. This isolate of human origin had a
      CIP MIC of 0.064 mg/L and DNA sequencing revealed that it contained an Asp87Gly
      gyrA mutation. Most of the remaining isolates had MICs for NAL and CIP of 256
      mg/L and 0.256 mg/L, respectively. Mutations in the Asp87 codon resulted in
      substitutions to Asn in most of the isolates, but Asp87Gly and Ser83Phe exchanges
      were also detected. No mutations were present in the gyrB, parC or parE genes.
      Although CIP resistance was absent, reduced susceptibility characterised by
      mutations in gyrA was apparent among S. Enteritidis isolates from Serbia.

PMID- 22999769
TI  - Factors influencing cervical cancer screening in women infected with HIV: a
      review of the literature.
AB  - The purpose of this article is to review and compare factors that influence
      cervical cancer screening behavior in HIV-infected women and uninfected women.
      The research literature revealed that age, ethnicity/race, tobacco use, weight,
      education, economic issues, and risky behaviors such as substance abuse were
      factors that influenced cervical cancer screening among all women. HIV viral load
      and CD4+ T lymphocyte count were serologic factors that affected cervical cancer
      screening in HIV-infected women. Clinicians can use this information to identify
      patients at risk for poor Pap test adherence. Future interventions to reduce
      potential barriers for cervical cancer screening are needed in HIV-infected
      women.

PMID- 22999770
TI  - Most relevant strategies for preventing surgical site infection after total hip
      arthroplasty: guideline recommendations and expert opinion.
AB  - BACKGROUND: Numerous strategies are available to prevent surgical site infections
      in hip arthroplasty, but there is no consensus on which might be the best. This
      study examined infection prevention strategies currently recommended for patients
      undergoing hip arthroplasty. METHODS: Four clinical guidelines on infection
      prevention/orthopedics were reviewed. Infection control practitioners, infectious
      disease physicians, and orthopedic surgeons were consulted through structured
      interviews and an online survey. Strategies were classified as "highly important"
      if they were recommended by at least one guideline and ranked as significantly or
      critically important by >=75% of the experts. RESULTS: The guideline review
      yielded 28 infection prevention measures, with 7 identified by experts as being
      highly important in this context: antibiotic prophylaxis, antiseptic skin
      preparation of patients, hand/forearm antisepsis by surgical staff, sterile
      gowns/surgical attire, ultraclean/laminar air operating theatres, antibiotic
      impregnated cement, and surveillance. Controversial measures included antibiotic
      impregnated cement and, considering recent literature, laminar air operating
      theatres. CONCLUSIONS: Some of these measures may already be accepted as routine
      clinical practice, whereas others are controversial. Whether these practices
      should be continued for this patient group will be informed by modeling the cost
      effectiveness of infection prevention strategies. This will allow predictions of
      long-term health and cost outcomes and thus inform decisions on how to best use
      scarce health care resources for infection control.

PMID- 22999771
TI  - Prevalence, risk factors, and molecular epidemiology of methicillin-resistant
      Staphylococcus aureus nasal and axillary colonization among psychiatric patients
      on admission to an academic medical center.
AB  - BACKGROUND: Infection control data from psychiatric units and clinics are
      limited. METHODS: This time series study was designed to determine the prevalence
      and risk factors for methicillin-resistant Staphylococcus aureus (MRSA)
      colonization and/or infection among 500 men and women on admission to psychiatric
      units at The Johns Hopkins Hospital. Discharge surveillance was conducted to
      measure incidence. Molecular characterization was performed. RESULTS: Five
      hundred subjects (52% male) were enrolled. The prevalence of MRSA colonization
      was 5.2% (26 of 498). Seven of 29 patients (24.1%) admitted with a skin and soft
      tissue infection (SSTI) was MRSA-positive; 4 of these patients had no other
      positive site, raising the total admission prevalence to 6.0%. A history of
      abscess (current or within the past 6 months) on admission (odds ratio [OR],
      6.06; 95% confidence interval [CI], 2.40-15.31; P < .001), HIV infection (OR,
      4.03; 95% CI, 1.52-10.71; P = .005), previous isolation (OR, 5.03; 95% CI, 1.76
      14.35; P = .003), and unknown history of isolation (OR, 4.10; 95% CI, 1.41-11.98;
      P = .01) were associated with increased odds of MRSA colonization. Seven (2.6%)
      new MRSA colonizations were identified at discharge. Molecular analysis
      identified USA300 clonal MRSA isolates. CONCLUSIONS: The prevalence of MRSA
      colonization in this study population was greater than reported in the general
      population. Further studies are needed to identify transmission dynamics in this
      environment.

PMID- 22999772
TI  - In vitro evaluation of cleaning efficacy of detergents recommended for use on
      dental instruments.
AB  - BACKGROUND: The cleaning stage of instrument decontamination processes is a
      critical control point, and removal of protein deposits is used as a marker of
      cleaning efficacy. An important factor is the choice of cleaning solution
      especially in the absence of any defined standards for detergent effectiveness.
      METHODS: Following method validation, stainless steel tokens were inoculated with
      reconstituted citrated blood and added to a 24-multiwell plate and immersed in
      different cleaning solutions for 5 minutes, agitated at 25 (20 degrees )
      tilts/min at 22 degrees C and at the manufacturers' recommended temperatures.
      Desorbed protein was measured using the bicinchoninic acid assay. RESULTS: From a
      starting concentration with a median of 3,700 MUg of blood protein of all
      solutions tested, alkaline detergent (Haemo-sol) removed the largest proportion
      of protein (median, 2,070 MUg), and surgical handwash removed the least protein
      (median, 0 MUg). Reverse osmosis water demonstrated useful blood-removing
      properties with a median of 1,421 MUg. CONCLUSION: The cleaning system we
      utilized is a simple, inexpensive method to compare the cleaning efficacies of
      detergents and may be used as a first stage in benchmarking cleaning efficacy of
      detergents. Not all solutions used in cleaning dental instruments are efficacious
      at removal of blood.

PMID- 22999773
TI  - Patient-level factors associated with methicillin-resistant Staphylococcus aureus
      carriage at hospital admission: a systematic review.
AB  - BACKGROUND: Selective methicillin-resistant Staphylococcus aureus (MRSA)
      screening programs target high-risk populations. To characterize high-risk
      populations, we conducted this systematic review to identify patient-level
      factors associated with MRSA carriage at hospital admission. METHODS: Studies
      were identified in the MEDLINE (1950-2011) and EMBASE (1980-2011) databases.
      English studies were included if they examined adult populations and used
      multivariable analyses to examine patient-level factors associated with MRSA
      carriage at hospital admission. From each study, we abstracted details of the
      population, the risk factors examined, and the association between the risk
      factors and MRSA carriage at hospital admission. RESULTS: Our electronic search
      identified 972 citations, from which we selected 27 studies meeting our inclusion
      criteria. The patient populations varied across the studies. Ten studies included
      all patients admitted to hospital, and the others were limited to specific
      hospital areas. MRSA detection methods also varied across studies. Ten studies
      obtained specimens from the nares only, whereas other studies also swabbed
      wounds, catheter sites, and the perianal region. Methods of MRSA diagnoses
      included polymerase chain reaction tests, cultures in various agar mediums, and
      latex agglutination tests. Patient age, gender, previous admission to hospital,
      and previous antibiotic use were the risk factors most commonly examined. The
      risk factor definition and study methods varied among studies to an extent that
      precluded meta-analysis. CONCLUSION: The existing literature cannot be used to
      identify risk factors for MRSA colonization at the time of hospitalization.
      Future studies should be aware of the differences in the existing literature and
      aim to develop standardized risk factor definitions.

PMID- 22999774
TI  - Combating malaria: the devil is in the molecular details.

PMID- 22999775
TI  - Predicting bloodstream infection via systemic inflammatory response syndrome or
      biochemistry.
AB  - BACKGROUND: The yield of blood cultures is approximately 10%. This could be
      caused by inaccurate prediction of patients with bloodstream infection (BSI).
      OBJECTIVES: To evaluate the usability of systemic inflammatory response syndrome
      (SIRS) or biochemical analyses as predictors for positive blood culture. METHODS:
      We conducted a prospective cohort study at a Danish regional hospital from
      February 1 to April 30, 2010. All adult patients were included on the first time
      blood cultures were sampled during admission. Data were obtained from medical
      records, databases on microbiology, biochemistry, and antibiotic treatment. Data
      included time of admission, date and result of blood culture, results of
      biochemical analyses, and clinical measurements on the day of blood culture.
      Prediction of BSI was analyzed according to both individual parameters and
      parameters combined in different sepsis score groups. Associations were
      calculated using multiple logistic regression. RESULTS: Patients with BSI (68
      patients) were compared to patients without BSI (828 patients). Respiratory rate,
      body temperature, and C-reactive protein were strongest associated with BSI, with
      adjusted odds ratio (OR) 5.42, 95% confidence interval (CI) 1.13-25.9; OR 2.55,
      95% CI 1.34-4.87; and OR 6.06, 95% CI 0.82-44.6, respectively. SIRS was
      associated with BSI, with crude OR 7.25, 95% CI 1.75-30.1. Neutrophil count and p
      carbamide were not associated with BSI: adjusted OR 0.88, 95% CI 0.36-2.13 and OR
      1.44, 95% CI 0.82-2.52, respectively. Only one of the sepsis score groups was
      associated with BSI: crude OR 2.13, 95% CI 1.08-4.19. CONCLUSIONS: SIRS is an
      adequate predictor of BSI. By contrast, biochemical parameters were not useful as
      predictors of BSI.

PMID- 22999776
TI  - Ketamine-induced catalepsy during adult sedation in the Emergency Department.
AB  - BACKGROUND: Ketamine continues to rise in popularity for procedural sedation in
      the Emergency Department (ED) for both adult and pediatric patients. The
      medication has a good safety profile and is well tolerated in the majority of
      patients. However, the Emergency Physician should be aware of the full range of
      side-effects that may be encountered, so as to best anticipate and prepare for
      potential complications. OBJECTIVES: We describe two cases of catalepsy (muscle
      hypertonia with dissociation) in patients undergoing sedation with ketamine. CASE
      REPORT: In the first case, a patient presented to the ED after a prehospital
      awake nasal intubation for an exacerbation of chronic obstructive pulmonary
      disease. After sedation with ketamine, he was extubated and transitioned to bi
      level positive pressure ventilation. Shortly after receiving ketamine, he
      exhibited severe muscular hypertonia of the upper extremities with facial
      grimacing. A second patient underwent ketamine sedation for reduction of a
      shoulder dislocation. After medication administration, he exhibited full body
      muscular hypertonicity, interfering briefly with the procedure. In both patients,
      catalepsy resolved spontaneously. CONCLUSIONS: Ketamine-induced catalepsy is a
      self-limited side-effect that has the potential to interfere with procedures
      performed under sedation.

PMID- 22999777
TI  - Fall from horse with left shoulder pain.

PMID- 22999778
TI  - Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind
      placebo-controlled study.
AB  - BACKGROUND: Acute alcohol withdrawal syndrome (AAWS) is encountered in patients
      presenting acutely to the Emergency Department (ED) and often requires
      pharmacologic management. OBJECTIVE: We investigated whether a single dose of
      intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based
      alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED
      patients with acute alcohol withdrawal. METHODS: This was a prospective,
      randomized, double-blind, placebo-controlled study. Patients were randomized to
      receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal
      saline) or placebo (100 mL normal saline). All patients were placed on the
      institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The
      primary outcome was initial level of hospital admission (ICU vs. telemetry vs.
      floor ward). RESULTS: There were 198 patients enrolled in the study, and 102 met
      inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51
      received placebo. Baseline characteristics and severity were similar in both
      groups. Patients that received phenobarbital had fewer ICU admissions (8% vs.
      25%, 95% confidence interval 4-32). There were no differences in adverse events.
      CONCLUSIONS: A single dose of i.v. phenobarbital combined with a symptom-guided
      lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission
      and did not cause increased adverse outcomes.

PMID- 22999779
TI  - A comparison of the impact of CPOE implementation and organizational determinants
      on doctor-nurse communications and cooperation.
AB  - OBJECTIVE: To compare the impact of CPOE implementation and of the workplace
      organizational determinants on the doctor-nurse cooperation and communication
      processes. METHOD: A first study was undertaken in eight different wards aimed to
      identify the different workplace organizations that support doctor-nurse
      communications'. A second study compared the impact of these organizations and of
      a CPOE on medication-related doctor-nurse communications. RESULTS: The doctor
      nurse communications could be structured into three typical workplace
      organizations: the common round, the briefing and the opportunistic exchange
      organizations. The results (i) confirmed the impact of the organizational
      determinants on the cooperative activities and (ii) demonstrated the CPOE system
      has no significant impact within a given workplace organization. CONCLUSION: The
      success of the implementation of HIT applications relies partly on the
      identification of the actual (and sometimes hidden) structuring variables of
      teamwork and ultimately on their control at the time of implementation to ensure
      the quality and safety of the patient care provided.

PMID- 22999780
TI  - 5-Aminosalicylates and renal function monitoring in inflammatory bowel disease: a
      nationwide survey.
AB  - BACKGROUND AND AIM: 5-Aminosalicylates (ASA) are widely used in inflammatory
      bowel disease (IBD). Nephrotoxicity has been described in some IBD patients
      treated with 5-ASA. Whether physicians managing these patients are monitoring
      renal function in daily practice is unknown. The aims of this paper were to
      investigate how private gastroenterologists monitor renal function and manage
      renal failure in IBD patients treated with oral 5-ASA therapy. METHODS: This was
      a web-based cross sectional national survey which was conducted among private
      gastroenterologists. RESULTS: A total of 249 practitioners completed the survey.
      Eighty two percent (n=205) of responders declared that they always monitor renal
      function. The respondents monitored twice a year Glomerular Filtration Rate
      (eGFR) using Modification of Diet in Renal Disease (MDRD) [90% (n=225)] and
      Creatinine Clearance (CCr) using a 24-hour urine collection [51% (n=126)]. Blood
      electrolytes, 24-hour urinary protein rate and dipsticks are performed by 41%,
      39% and 22% of practitioners, respectively. Before oral 5-ASA initiation, 59%
      (n=148) of respondents screen for renal failure. In case of elevated serum
      creatinine, a nephrologist's opinion is asked by 80% (n=200) of responders and by
      76% (n=189) of respondents before treatment initiation. CONCLUSIONS: Most
      gastroenterologists are monitoring renal function once or twice a year in IBD
      patients on 5-ASA. Less than two thirds of them screen for renal failure before
      treatment initiation. MDRD is mainly used, but a wide range of parameters is
      evaluated.

PMID- 22999781
TI  - Enzymes involved in L-carnitine biosynthesis are expressed by small intestinal
      enterocytes in mice: implications for gut health.
AB  - BACKGROUND: Carnitine is essential for mitochondrial beta-oxidation of long-chain
      fatty acids. Deficiency of carnitine leads to severe gut atrophy, ulceration and
      inflammation in animal models of carnitine deficiency. Genetic studies in large
      populations have linked mutations in the carnitine transporters OCTN1 and OCTN2
      with Crohn's disease (CD), while other studies at the same time have failed to
      show a similar association and report normal serum carnitine levels in CD
      patients. METHODS: In this report, we have studied the expression of carnitine
      synthesizing enzymes in intestinal epithelial cells to determine the capability
      of these cells to synthesize carnitine de novo. We studied expression of five
      enzymes involved in carnitine biosynthesis, namely 6-N-trimethyllysine
      dioxygenase (TMLD), 4-trimethylaminobutyraldehyde dehydrogenase (TMABADH), serine
      hydroxymethyltransferase 1 and 2 (SHMT1 and 2) and gamma-butyrobetaine
      hydroxylase (BBH) by real-time PCR in mice (C3H strain). We also measured
      activity of gamma-BBH in the intestine using an ex vivo assay and localized its
      expression by in situ hybridization. RESULTS: Our investigations show that mouse
      intestinal epithelium expresses all five enzymes required for de novo carnitine
      biosynthesis; the expression is localized mainly in villous surface epithelial
      cells throughout the intestine. The final rate-limiting enzyme gamma-BBH is
      highly active in the small intestine; its activity was 9.7 +/- 3.5 pmol/mg/min,
      compared to 22.7 +/- 7.3 pmol/mg/min in the liver. CONCLUSIONS: We conclude that
      mouse gut epithelium is able to synthesize carnitine de novo. This capacity to
      synthesize carnitine in the intestine may play an important role in gut health
      and can help explain lack of clinical carnitine deficiency signs in subjects with
      mutations with OCTN transporters.

PMID- 22999783
TI  - Major ambulatory medicine.

PMID- 22999782
TI  - Novel risk markers and long-term outcomes of delirium: the successful aging after
      elective surgery (SAGES) study design and methods.
AB  - OBJECTIVES: Delirium, a costly, life-threatening, and potentially preventable
      condition, is a common complication for older adults following major surgery.
      Although the basic epidemiology of delirium after surgery has been defined, the
      contribution of delirium to long term outcomes remains uncertain, and novel
      biomarkers from plasma and neuroimaging have yet to be examined. This program
      project was designed to contribute to our understanding of the complex
      multifactorial syndrome of delirium. DESIGN: Long term prospective cohort study.
      SETTING: Three academic medical centers (2 hospitals and 1 coordinating center).
      PARTICIPANTS: Patients without recognized dementia (targeted cohort= 550
      patients) age 70 and older scheduled to undergo elective major surgery are
      assessed at baseline before surgery, daily during their hospital stay, and for 18
      to 36 months after discharge. MEASUREMENTS: The Successful Aging after Elective
      Surgery (SAGES) study is an innovative, interdisciplinary study that includes
      biomarkers, neuroimaging, cognitive reserve markers, and serial
      neuropsychological testing to examine the contribution of delirium to long term
      cognitive and functional decline. The primary goal is to examine the contribution
      of delirium to long term cognitive and functional decline. In addition, novel
      risk markers for delirium are being examined, including plasma biomarkers (eg,
      cytokines, proteomics), advanced neuroimaging markers (eg, volumetric, white
      matter hyperintensity, noncontrast blood flow, and diffusion tensor measures),
      and cognitive reserve markers (eg, education, occupation, lifetime activities).
      CONCLUSION: Results from this study will contribute to a fuller understanding of
      the etiology and prognosis of delirium. Ultimately, we hope this project will
      provide the groundwork for future development of prevention and treatment
      strategies for delirium, designed to minimize the long term negative impact of
      delirium in older adults.

PMID- 22999784
TI  - Effects of single bout of very high-intensity exercise on metabolic health
      biomarkers in overweight/obese sedentary men.
AB  - PURPOSE: This study aimed to investigate the effects of a single session of
      sprint interval training (SIT) and a single extended sprint (ES), matched for
      total work, on metabolic health biomarkers. METHODS: Ten overweight/obese men
      aged 26.9+/-6.2years participated. Following a pre-trial incremental exercise
      test and SIT familiarization, each participant undertook three 2-day trials in
      randomized order. On Day 1 participants either undertook no exercise (CON), four
      maximal 30-s sprints, with 4.5min recovery between each (SIT), or a single
      maximal extended sprint (ES) matched with SIT for work done. On Day 2,
      participants had a fasting blood sample taken, undertook an oral glucose
      tolerance test to determine insulin sensitivity index (ISI), and had blood
      pressure measured. RESULTS: Total work done during exercise did not differ
      between SIT and ES (61.7+/-2.9 vs. 61.3+/-2.8kJ; p=0.741). Mean power was higher
      in SIT than ES (518+/-21 vs. 306+/-16W, p<0.0005), resulting in a shorter high
      intensity exercise duration in SIT (120+/-0 vs. 198+/-10s, p<0.0005). ISI was
      44.6% higher following ES than CON (9.4+/-2.1 vs. 6.5+/-1.3; p=0.022), but did
      not differ significantly between SIT and CON (6.6+/-0.9 vs. 6.5+/-1.3; p=0.208).
      However, on the day following exercise fat oxidation in the fasted state was
      increased by 63% and 38%, compared to CON, in SIT and ES, respectively (p<0.05
      for both), with a concomitant reduction in carbohydrate oxidation (p<0.05).
      CONCLUSION: A single ES, which may represent a more time-efficient alternative to
      SIT, can increase insulin sensitivity and increase fat oxidation in overweight
      overweight/obese sedentary men.

PMID- 22999785
TI  - The complex interaction between obesity, metabolic syndrome and reproductive
      axis: a narrative review.
AB  - The aim of this narrative review is to provide current evidence for the
      interaction between obesity, metabolic syndrome (MS) and reproductive axis.
      Gonadotropin-releasing hormone (GnRH) pulses and, consequently, normal function
      of reproductive (hypothalamus-pituitary-gonadal) axis depend on normal energy
      balance, which presupposes sufficient food intake, reasonable energy consumption
      and average thermoregulatory costs. In case of an energy imbalance, reproductive
      dysfunction may occur. In young women, excessive leanness is accompanied by
      puberty delay, whereas premature puberty might be a manifestation of obesity. In
      a similar way, obesity in men affects fertility. Excess adipose tissue results in
      increased conversion of testosterone to estradiol, which may lead to secondary
      hypogonadism through reproductive axis suppression. Moreover, oxidative stress at
      the level of the testicular micro-environment may result in decreased
      spermatogenesis and sperm damage. Products of the adipocyte, such as leptin,
      adiponectin and resistin, and gut peptides, such as ghrelin, are considered to be
      crucial in the interaction between energy balance and reproduction. Finally, an
      indirect evidence for the interplay between MS and reproductive axis is the fact
      that when treating components of one, parameters of the other can be improved as
      well. These therapeutic interventions include lifestyle modifications,
      pharmacological agents, such as sex hormone replacement therapy, and surgical
      procedures. Although many issues remain unclear, the elucidation of the complex
      interaction between MS and reproductive axis will have obvious clinical
      implications in the therapeutic approach of both entities.

PMID- 22999787
TI  - A long journey home.

PMID- 22999786
TI  - Is there shared decision making when the provider makes a recommendation?
AB  - OBJECTIVE: To compare the amount of shared decision making in breast cancer
      surgery interactions when providers do and do not make a treatment
      recommendation. METHODS: We surveyed breast cancer survivors who were eligible
      for mastectomy and lumpectomy. Patients reported whether the provider made a
      recommendation and the recommendation given. They completed items about their
      interaction including discussion of options, pros, cons, and treatment
      preference. A total involvement score was calculated with higher scores
      indicating more shared decision making. RESULTS: Most patients (85%) reported
      that their provider made a recommendation. Patients who did not receive a
      recommendation had higher involvement scores compared to those who did (52% vs.
      39.1%, p=0.004). Type of recommendation was associated with involvement. Patients
      given different recommendations had the highest total involvement scores followed
      by those who received mastectomy and lumpectomy recommendations (65.5% vs. 42.5%
      vs. 33.2%, respectively, p<0.001). CONCLUSION: Providers were less likely to
      present a balanced view of the options when they gave a recommendation for
      surgery. Patients who received a recommendation for lumpectomy had the lowest
      involvement score. PRACTICE IMPLICATIONS: Providers need to discuss both
      mastectomy and lumpectomy and elicit patients' goals and treatment preferences
      regardless of whether or not a recommendation is given.

PMID- 22999789
TI  - A case of Histoplasma capsulatum endophthalmitis diagnosed in Italy.
AB  - Histoplasma capsulatum var. capsulatum is a dimorphic fungus endemic in the
      eastern United States and most countries of Latin America. Sporadic cases of
      histoplasmosis have been reported in Europe, mainly in immigrants or people
      returning from highly endemic areas. We report a case of 64-year-old Italian man
      with endophthalmitis, an unusual presentation of H. capsulatum infection. The
      patient shows redness, blurred vision, localized pain in the right eye. H.
      capsulatum was cultured from a vitreous biopsy and yeast forms were seen at
      histology. 

PMID- 22999788
TI  - Long-term selective IgE-mediated hypersensitivity to hydrocortisone sodium
      succinate.

PMID- 22999790
TI  - Proinflammatory cytokines induced altered expression of cyclooxygenase-2 gene
      results in unreceptive endometrium in women with idiopathic recurrent spontaneous
      miscarriage.
AB  - OBJECTIVE: To investigate the expression pattern of proinflammatory, anti
      inflammatory, and angiogenic cytokines and their effect on various mediators of
      endometrial receptivity in women with idiopathic recurrent spontaneous
      miscarriage (IRSM). DESIGN: A prospective study. SETTING: Tertiary care hospital
      and reproductive health research unit. PATIENT(S): Thirty-six women with IRSM
      (<35 years) and 30 fertile women as controls matched by age and body mass index
      undergoing sterilization. INTERVENTION(S): Endometrial biopsies in all women
      corresponding to the window of implantation. MAIN OUTCOME MEASURE(S): Assessment
      of endometrial expression of proinflammatory, anti-inflammatory, and angiogenic
      cytokines, mediators of matrix turnover and angiogenesis, markers of receptivity.
      RESULT(S): A statistical significantly higher level of proinflammatory cytokines,
      mediators of matrix turnover and angiogenesis, and a reduced expression of anti
      inflammatory and angiogenic cytokines were observed in women with IRSM.
      Additionally, the markers of endometrial receptivity were poorly expressed in
      women with IRSM. CONCLUSION(S): Aberrant expression of proinflammatory, anti
      inflammatory, and angiogenic cytokines during implantation window in women with
      IRSM is one of the key factors that adversely affect endometrial development, as
      evidenced by the inadequate expression of various endometrial receptivity
      markers.

PMID- 22999791
TI  - Chromosomal analysis is still indicated for men with severely impaired sperm
      production.

PMID- 22999792
TI  - Aromatase inhibitors for the treatment of endometriosis.
AB  - OBJECTIVE: To review the use of aromatase inhibitors (AIs) for the treatment of
      endometriosis. DESIGN: Literature review. CONCLUSION(S): Most studies show that
      in reproductive-age women, the combination of AI with conventional therapy
      alleviates endometriosis-related pain. In postmenopausal women, using an AI alone
      has been shown to be an effective treatment, although more studies are needed in
      this subgroup. Side effects of using AIs appear to be tolerable in most women,
      although special consideration should be given to monitoring bone mineral
      density. More studies need to be done examining pregnancy rates and outcomes
      after AI treatment for endometriosis. In addition, larger randomized clinical
      trials using AIs need to be done. In summary, AIs may be effective in treating
      endometriosis-related chronic pelvic pain in both reproductive-age and
      postmenopausal women.

PMID- 22999793
TI  - Free carnitine and acylcarnitines in obese patients with polycystic ovary
      syndrome and effects of pioglitazone treatment.
AB  - OBJECTIVE: To determine fasting and insulin-stimulated levels of carnitine
      precursors, total and free carnitine, and acylcarnitines, and evaluate the impact
      of pioglitazone treatment in obese patients with polycystic ovary syndrome
      (PCOS). DESIGN: The present study is a secondary analysis of a previously
      published case-control study, followed by a double-blind randomized clinical
      trial. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty obese
      premenopausal patients with PCOS and 14 healthy women. INTERVENTION(S): Sixteen
      weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME
      MEASURE(S): Total and free carnitine and acylcarnitines. RESULT(S): Contrary to
      controls, patients with PCOS were characterized with slightly lower levels of
      fasting total and free carnitine, its precursors, and derivatives. Total and free
      carnitine correlated inversely to sex hormone-binding globulin (SHBG) in patients
      with PCOS, whereas no associations were found between acylcarnitines and
      androgenes. Insulin stimulation-induced changes in the levels of total and free
      carnitine, carnitine precursors, and acylcarnitines in the PCOS group followed
      the same trends as in the control group. Pioglitazone treatment significantly
      increased fasting levels of serum-free carnitine, propionyl carnitine, and total
      carnitine. The analysis of between group differences revealed significant changes
      in the isovaleryl carnitine levels and lipid oxidation rates after pioglitazone
      treatment compared with placebo. CONCLUSION(S): Acute insulin stimulation was
      associated with increased serum levels of free carnitine in both patients and
      healthy controls. Treatment with pioglitazone is able to redistribute free fatty
      acids from insulin-sensitive tissues, diminish demand for carnitine, and
      influence the overall carnitine turnover. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT00145340.

PMID- 22999794
TI  - Significantly lower ectopic pregnancy rates after frozen embryo transfer:
      implications toward segmentation of in vitro fertilization treatment.

PMID- 22999795
TI  - Dysmenorrhea and its severity are associated with increased uterine contractility
      and overexpression of oxytocin receptor (OTR) in women with symptomatic
      adenomyosis.
AB  - OBJECTIVE: To evaluate uterine contractility, oxytocin receptor (OTR) expression
      in myometrial smooth muscle cells (MSMCs) derived from uterine tissues from women
      with and without adenomyosis correlate OTR expression with uterine contractility
      and dysmenorrhea severity, and see whether trichostatin A (TSA) and
      andrographolide inhibit OTR expression. DESIGN: Laboratory study using human
      tissues. SETTING: Academic hospital. PATIENT(S): Twenty patients (cases) with
      histologically confirmed adenomyosis and 10 (controls) with leiomyomas, cervical
      dysplasia, and cancer but no adenomyosis or endometriosis. INTERVENTION(S):
      Dysmenorrhea severity was scored by Visual Analog Scale. Uterine tissue samples
      were collected during hysterectomy. Myometrial smooth muscle cells derived from
      tissue samples were cultured and OTR protein levels were measured. The effect of
      TSA (0.5 or 1 MUM) and andrographolide (15 or 30 MUM) on OTR expression was
      evaluated. MAIN OUTCOME MEASURE(S): Visual Analog Scale scores, and contractile
      amplitude and frequency. The OTR protein levels in MSMCs were quantified by
      Western blot analysis. RESULT(S): The contractile amplitude and OTR expression
      levels were significantly higher in cases than in controls. Dysmenorrhea Visual
      Analog Scale scores correlated positively with contractile amplitude and OTR
      expression level. Both TSA and andrographolide dose-dependently inhibit OTR
      expression in MSMC. CONCLUSION(S): Oxytocin receptor overexpression in MSMCs may
      be responsible for increased uterine contractility and adenomyosis-associated
      dysmenorrhea. Both histone deacetylase inhibitors and andrographolide are
      therapeutically promising.

PMID- 22999796
TI  - Perfringolysin O as a useful tool to study human sperm physiology.
AB  - OBJECTIVE: To evaluate perfringolysin O, a cholesterol-dependent pore-forming
      cytolysin, as a tool to study several aspects of human sperm physiology. DESIGN:
      Prospective study. SETTING: Basic research laboratory. PATIENT(S): Human semen
      samples with normal parameters obtained from healthy donors. INTERVENTION(S):
      Interaction of recombinant perfringolysin O with human spermatozoa. MAIN OUTCOME
      MEASURE(S): Assessment of perfringolysin O binding to spermatozoa, tests for
      acrosome and plasma membrane integrity, and acrosomal exocytosis assays.
      RESULT(S): Perfringolysin O associated with human spermatozoa at 4 degrees C. The
      binding was sensitive to changes in cholesterol concentrations and distribution
      occurring in the plasma membrane of these cells during capacitation. When
      perfringolysin O-treated sperm were incubated at 37 degrees C, the plasma
      membrane became permeable, whereas the acrosome membrane remained intact.
      Permeabilized spermatozoa were able to respond to exocytic stimuli. The process
      was inhibited by proteins that interfere with membrane fusion, indicating that
      large molecules, including antibodies, were able to permeate into the
      spermatozoa. CONCLUSION(S): PFO is a useful probe to assess changes in the amount
      and distribution of the active sterol fraction present in the sperm plasma
      membrane. The toxin can be used for the efficient and selective permeabilization
      of this membrane, rendering a flexible experimental model suitable for studying
      molecular processes occurring in the sperm cytoplasm.

PMID- 22999797
TI  - Clomiphene citrate potentiates the adverse effects of estrogen on rat testis and
      down-regulates the expression of steroidogenic enzyme genes.
AB  - OBJECTIVE: To investigate the antiestrogenic effect of clomiphene citrate (CC) in
      male rats estrogenized with estradiol-3-benzoate (EB). DESIGN: Prospective
      experimental study. SETTING: Laboratory. ANIMALS: Adult male albino rats
      (Holtzman strain). INTERVENTION(S): CC was given alone or in combination with EB.
      MAIN OUTCOME MEASURE(S): Testicular function and steroidogenic enzyme gene
      expression were evaluated in control versus treated groups. RESULT(S): EB after
      30 days of treatment induced a rise in TUNEL-positive germ cells adversely
      affecting spermatogenesis with complete absence of elongated spermatids or
      sperms. CC alone had only a moderate effect. In contrast, CC+EB synergistically
      inflicted more adverse effects as apoptotic germ cells per tubule rose further.
      Significant down-regulation in expression of testicular steroidogenic enzyme
      genes StAR, p450scc, 3beta-HSD, and p450c17 was observed. In the EB-alone group,
      aromatase gene expression in the testis was up-regulated but reversed in brain
      and liver tissues. CC alone had little modulatory effect on aromatase expression.
      On the other hand, CC+EB countered the EB-induced rise of aromatase expression in
      the testis. CONCLUSION(S): The above findings indicate that CC in the presence of
      estrogen synergistically potentiates more adverse effects in testis, inhibiting
      expression of upstream steroidogenic enzyme genes and leading to disruption of
      steroidogenesis.

PMID- 22999798
TI  - Relationships between the luteinizing hormone surge and other characteristics of
      the menstrual cycle in normally ovulating women.
AB  - OBJECTIVE: To describe the LH surge variants in ovulating women and analyze their
      relationship with the day of ovulation and other hormone levels. DESIGN:
      Secondary analysis of a prospective cohort observational study. SETTING: Eight
      natural family planning clinics. SUBJECTS: Normally fertile women (n = 107) over
      283 cycles. INTERVENTION(S): Women collected daily first morning urine, charted
      basal body temperature and cervical mucus discharge, and underwent serial ovarian
      ultrasound. MAIN OUTCOME MEASURE(S): Urinary LH, FSH, estrone-3-glucuronide
      (E3G), pregnanediol-3alpha-glucuronide (PDG), and day of ovulation by ultrasound
      (US-DO). RESULT(S): Individual LH surges were extremely variable in
      configuration, amplitude, and duration. The study also showed that LH surges
      marked by several peaks were associated with statistically significant smaller
      follicle sizes before rupture and lower LH level on the day of ovulation. LH
      surges lasting >3 days after ovulation were associated with a lower E3G before
      ovulation, a smaller corpus luteum 2 days after ovulation, and a lower PDG value
      during the first 4 days after ovulation. CONCLUSION(S): In clinical practice, LH
      profiles should be compared with the range of profiles observed in normally
      fertile cycles, not with the mean profile.

PMID- 22999799
TI  - [Estimate of the real incidence of tuberculosis in the Leon Health Area:
      application of the capture-recapture method to compare two information sources].
AB  - INTRODUCTION: The actual incidence of tuberculosis is probably higher than that
      previously published in national and international records. Under-reporting is
      estimated to fluctuate between 7% and 27%, according to studies. OBJECTIVE: To
      estimate the incidence rate of tuberculosis in the area of Leon for 2008 and 2009
      using the capture-recapture method in order to compare two sources of
      information: prescribed tuberculostatic drugs (combination of rifampicin
      isoniazid) and the regional epidemiological surveillance system register (SIVE).
      METHOD: Retrospective descriptive study in an area of 351,086 inhabitants of
      tuberculosis cases using as sources: (i), information on prescribed
      tuberculostatic drugs, and (ii), the SIVE register. We calculated incidence rates
      for each source by the capture-recapture method. We analyzed epidemiological and
      demographic data, symptoms, diagnosis, treatment and follow-up. RESULTS: The
      incidence based on the SIVE data for 2008 was 18.80/100,000 inhabitants and
      according to the pharmacy register, the rate was 26.77. The estimated value for
      2009 based on the SIVE data was 18.23/100,000 inhabitants, and according to the
      pharmacy register, it was 22.50. After applying the capture-recapture method, the
      annual incidence for 2008 was 44.14/100,000 (95% CI; 37.88-50.41) and for 2009,
      it was 34.17/100,000 (95% CI; 30.19-38.17). In the study of all these years we
      have found that the number of cases were higher in the pharmacy register than the
      SIVE one. CONCLUSIONS: The SIVE data on the incidence of tuberculosis in our
      study area underestimates the actual incidence rate. The source of information
      that involves case record of tuberculosis in the community is under-used. The
      capture-recapture method is a good alternative to measure the incidence of
      tuberculosis, and to check the surveillance systems.

PMID- 22999800
TI  - Viral hepatitis: global goals for vaccination.
AB  - In countries where hepatitis A is highly endemic, exposure to hepatitis A virus
      (HAV) is almost universal before the age of 10 years, and large-scale
      immunization efforts are not required. In contrast, in areas of intermediate
      endemicity or in transition from high to intermediate endemicity, where
      transmission occurs primarily from person to person in the general community
      (often with periodic outbreaks), control of hepatitis A may be achieved through
      widespread vaccination programmes. Hepatitis B virus (HBV) is one of the world's
      most widespread infectious agents and the cause of millions of infections each
      year. Between 500,000 and 700,000 people die each year from chronic infection
      related cirrhosis, hepatocellular carcinoma (HCC) or from acute hepatitis B.
      Hepatitis B vaccine provides protection against infection and its complications
      including liver cirrhosis and HCC. It is therefore, the first vaccine against a
      cancer, the first vaccine protecting from a sexually transmitted infection, and
      the first vaccine against a chronic disease ever licensed. Control and
      significant reduction in incidence of new HBV infections as well as
      hepatocellular carcinoma has repeatedly been reported in countries in East Asia
      (i.e. Taiwan) and Africa (i.e. The Gambia). Two experimental vaccines against
      hepatitis E have been developed; one of them has been recently licensed but is
      not yet widely available. Attempts to develop a hepatitis C vaccine were so far
      unsuccessful.

PMID- 22999801
TI  - Flaviviruses and their antigenic structure.
AB  - Flaviviruses comprise important arthropod-transmitted human pathogens, including
      yellow fever (YF), dengue (Den), Japanese encephalitis (JE), West Nile (WN) and
      tick-borne encephalitis (TBE) viruses that have the potential of expanding their
      endemic areas due to global climatic, ecological and socio-economic changes.
      While effective vaccines against YF, JE and TBE are in widespread use, the
      development of a dengue vaccine has been hampered for a long time because of
      concerns of immunopathological consequences of vaccination. Phase III clinical
      trials with a recombinant chimeric live vaccine are now ongoing and will show
      whether the enormous problem of dengue can be resolved or at least reduced by
      vaccination in the future. Unprecedented details of the flavivirus particle
      structure have become available through the combined use of X-ray crystallography
      and cryo-electron microscopy that led to novel and surprising insights into the
      antigenic structure of these viruses. Recent studies provided evidence for an
      important role of virus maturation as well as particle dynamics in virus
      neutralization by antibodies and thus added previously unknown layers of
      complexity to our understanding of flavivirus immune protection. This information
      is invaluable for interpreting current investigations on the functional
      activities of polyclonal antibody responses to flavivirus infections and
      vaccinations and may open new avenues for studies on flavivirus cell biology and
      vaccine design.

PMID- 22999802
TI  - Pharmacy students' opinions of direct-to-consumer advertising: a pilot study at
      one university.
AB  - BACKGROUND: Direct-to-consumer advertisement (DTCA) of prescription medications
      has become an important informational source for health care consumers. As future
      health care professionals on the front line of potential communication and
      dispensing of products emerging from DTCA, it is important to elicit the
      attitudes of student-pharmacists. OBJECTIVES: This study aims to (1) evaluate the
      validity of the DTCA attitudinal questionnaire using Rasch rating scale analysis
      and (2) investigate the attitudes of pharmacy students toward DTCA and determine
      whether these attitudes were associated with years of pharmacy education and
      demographic characteristics. METHODS: This investigation used a cross-sectional
      print-based questionnaire to evaluate the attitudes of pharmacy students toward
      DTCA of prescription medications. The 16-item questionnaire included items
      addressing the attitudes of pharmacy students toward DTCA with respect to
      patients' knowledge of medications, pharmacists' interaction with patients, and
      overall consumer judgment of medical prescriptions. Analyses included Rasch
      analysis and a multiple linear regression. RESULTS: A total of 243 students
      submitted usable questionnaires (85% response rate). Item response categories
      were collapsed from 5 categories to 3, and 4 items were removed to achieve
      acceptable Rasch model fit. Pharmacy students demonstrated little difficulty in
      agreeing with the statements suggesting that DTCA helps patients take a more
      active role in health care and had the most difficulty in agreeing with items
      suggesting that DTCA may lead to inappropriate prescribing to satisfy patient
      requests. Students' overall support for DTCA was the only variable that predicted
      the questionnaire score (P<.001). CONCLUSIONS: In conclusion, the Rasch analysis
      evaluated the psychometric properties of the instrument and identified the
      necessity to adapt the questionnaire from previous iterations to adequately fit
      the student population. Future research should examine factors that contribute to
      the variance in attitudes toward DTCA among a larger and more heterogeneous
      population.

PMID- 22999803
TI  - Evaluation of the impact of a continuing professional development worksheet on
      sustained learning and implementing change after a continuing pharmacy education
      activity.
AB  - BACKGROUND: Continuing professional development (CPD) continues to gain
      acceptance as a model for health care professionals to engage in lifelong
      learning. Little is known about how CPD participants use the experience to
      develop learning plans and implement new knowledge into practice. OBJECTIVE: The
      primary objective of this study was to evaluate the effectiveness of instruments
      designed to guide the pharmacist through a CPD process to plan and participate in
      continuing professional education activities at a national meeting. METHODS: The
      study was a case-control study of pharmacists randomized from the participants of
      the 2010 American Pharmacists Association Annual Meeting. The test group (n=47)
      was instructed to complete CPD planning worksheets designed to facilitate
      planning of their continuing pharmacy education activities before the meeting.
      The control group (n=58) did not have instructions beyond the meeting program.
      Both groups completed 3 surveys assessing components of the CPD processes: 1
      before and 2 after the meeting. The surveys focused on confidence in abilities to
      identify, plan, and evaluate learning as well as implementation of practice
      change. RESULTS: Nearly all the test groups reported successful application of
      learning (95%) and achieving their designed learning plan (87%). Practice changes
      were implemented in more than half (60%) of the test groups after using a CPD
      process to plan their learning activities. There were no significant differences
      among groups regarding the outcome measures. CONCLUSIONS: Participants
      successfully used a CPD approach to meet their learning plans and achieve
      meaningful learning outcomes. Integration of CPD components into educational
      activities may help to promote practice change.

PMID- 22999804
TI  - Consumers' willingness to use a medication management service: the effect of
      medication-related worry and the social influence of the general practitioner.
AB  - BACKGROUND: Some consumers at risk of experiencing medication-related problems
      have chosen not to use pharmacist-provided medication management services.
      Previous research has shown that consumers' willingness to use the Australian
      Home Medicines Review (HMR) service depends on the extent to which they believe
      that they will receive medication information to assist them with self
      management. OBJECTIVES: The aim of this study was to develop and test a model of
      willingness to use HMR among consumers who were eligible to receive the service
      but have not yet experienced it. Specifically, this study aimed to determine the
      effects of consumers' medication-related worry and the social influence of the
      consumer's general practitioner (GP) over willingness. METHODS: A cross-sectional
      postal survey was conducted among 1600 members of Council on the Ageing (NSW,
      Australia). Respondents were included in the study if they had not experienced an
      HMR and were taking more than 5 medicines daily or more than 12 doses daily.
      Measurement scales were developed or were based on previous research.
      Confirmatory factor analysis was used to test the reliability and validity of the
      multi-item scales. Multiple regression analysis and structural equation modeling
      (SEM) were used to test the model. RESULTS: Surveys received from 390 respondents
      (24.3%) were analyzed. Respondents held overall low-to-neutral positive outcome
      expectancy (POE). The SEM analysis revealed that worry had a direct effect on POE
      (beta=0.35, P<.05) and an indirect effect on willingness (beta=0.22, P<.05).
      Subjective norms had a direct effect on willingness (beta=0.27, P<.05) but not
      POE. Worry was higher among those who had experienced a change in the medication
      regimen within the past 3 months (beta=0.19, P<.001). CONCLUSIONS: Those
      consumers who were worried about their medicines were more willing to use HMR.
      The consumer's GP appeared to exert a significant positive social influence over
      willingness to use this medication management service.

PMID- 22999805
TI  - Concern beliefs in medications: changes over time and medication use factors
      related to a change in beliefs.
AB  - BACKGROUND: Concern belief in medication is a construct that may characterize
      patients' attitude toward managing medicines, and this could change with time.
      Understanding the factors that would impact a change in concern beliefs would be
      helpful in interventions that could reframe patients' perceptions about their
      medicines. OBJECTIVES: To examine if patient concern beliefs in medications
      change over time, assess the characteristics of individuals whose beliefs change,
      and determine what factors might impact a change in patient beliefs. METHODS:
      Secondary data analysis using 2 longitudinal studies. The first study was an
      Internet-based survey of Medicare enrollees pre-post Medicare Part D. The second
      study was a randomized controlled trial evaluating a medication management
      intervention among adults with physical limitations. Respondents were classified
      as those whose beliefs remained stable and those whose beliefs increased and
      decreased over 2 separate periods. Chi-square analysis examined significant
      differences across the groups. Multiple linear regressions examined factors that
      influence changes in patient beliefs. RESULTS: Among older adults, there were
      differences in perceived health status (chi(2)=26.05, P=.001), number of
      pharmacies used (chi(2)=17.41, P=.008), and number of medicines used after the
      start of Medicare Part D. There were no significant differences among adults with
      physical limitations. Among older adults, having an increased number of medicines
      over time and reporting a self-reported adverse effect to a physician were
      positively associated with an increase in concern beliefs in medication. Having
      an increase in adherence was associated with a decrease in concern beliefs over
      time. CONCLUSION: Concern beliefs in medications may contribute independent
      information about individuals' response to drug programs and policies. Outcomes
      of medication use may influence patient anxieties about medicines. The
      instability of patient concerns in medications that occurs with prescription drug
      coverage changes, and the emergence of adverse outcomes of medication use may
      provide insight into the development of individualized interventions.

PMID- 22999807
TI  - Telestroke: time is brain and the time is now.

PMID- 22999806
TI  - The neurotoxic effect of astrocytes activated with toll-like receptor ligands.
AB  - Toll-like receptors (TLRs) are key molecules in the innate immune system in the
      central nervous system. Although astrocytes are believed to play physiological
      roles in regulating neuronal activity and synaptic transmission, activated
      astrocytes may also be toxic to neurons. Here, we show that the ligands for TLRs
      2, 4, 5 and 6 induce neuronal cell death in neuron-astrocytes co-cultures through
      the production of reactive oxygen species (ROS). Inhibition of ROS production by
      NADPH oxidase inhibitor apocynin significantly suppresses neuronal cell death.
      ROS induced in astrocytes via TLRs may be involved in neuroinflammation and a
      therapeutic target for neurotoxicity by activated astrocytes.

PMID- 22999808
TI  - Walking exercise response to bronchodilation in mild COPD: a randomized trial.
AB  - RATIONALE: Patients with mild chronic obstructive pulmonary disease (COPD)
      present abnormal ventilatory mechanics during exercise and may require
      bronchodilator therapy. However, bronchodilation does not enhance cycling
      exercise tolerance in these patients whereas walking may be more sensitive to the
      effects of bronchodilation. OBJECTIVES: To characterize the impact of
      bronchodilation on i) exercise tolerance ii) cardiopulmonary response and iii)
      dynamic hyperinflation following an endurance shuttle walking test in patients
      with mild COPD. METHODS: In a randomized double-blind cross-over trial, 37
      patients with GOLD stage I COPD (FEV(1), 96 +/- 2% predicted, mean +/- SEM)
      completed an endurance shuttle walking test up to exhaustion 90 +/- 15 min
      following nebulization of a placebo [NaCl] or of ipratropium bromide/salbutamol
      sulfate (500 MUg/2.5 mg) combination. RESULTS: FEV(1) significantly increased
      following bronchodilation compared with placebo (0.17 +/- 0.02 vs. -0.02 +/- 0.01
      L, p < 0.0001, mean +/- SEM). The difference in walking endurance time between
      bronchodilation and placebo was not statistically significant (Delta15 +/- 12 s,
      p = 0.21), with the upper and lower boundaries of the 95% confidence interval [-9
      40 s, 95% CI] within the proposed minimally important difference for this
      variable (65 s). The ratio of breathing frequency to tidal volume tended to be
      decreased with bronchodilation during exercise (p = 0.07), indicating a deeper
      and slower breathing pattern with bronchodilation. Bronchodilation had a
      significant effect on dynamic hyperinflation at isotime and at peak exercise.
      CONCLUSION: Bronchodilation did not improve walking endurance in patients with
      mild COPD despite small physiological benefits of uncertain clinical relevance.

PMID- 22999809
TI  - Floral scent in bird- and beetle-pollinated Protea species (Proteaceae):
      chemistry, emission rates and function.
AB  - Evolutionary shifts between pollination systems are often accompanied by
      modifications of floral traits, including olfactory cues. We investigated the
      implications of a shift from passerine bird to beetle pollination in Protea for
      floral scent chemistry, and also explored the functional significance of Protea
      scent for pollinator attraction. Using headspace sampling and gas chromatography
      mass spectrometry, we found distinct differences in the emission rates and
      chemical composition of floral scents between eight bird- and four beetle
      pollinated species. The amount of scent emitted from inflorescences of beetle
      pollinated species was, on average, about 10-fold greater than that of bird
      pollinated species. Floral scent of bird-pollinated species consists mainly of
      small amounts of "green-leaf volatiles" and benzenoid compounds, including
      benzaldehyde, anisole and benzyl alcohol. The floral scent of beetle-pollinated
      species is dominated by emissions of linalool, a wide variety of other
      monoterpenes and the benzenoid methyl benzoate, which imparts a fruity odour to
      the human nose. The number of compounds recorded in the scent of beetle
      pollinated species was, on average, greater than in bird-pollinated species (45
      versus 29 compounds, respectively). Choice experiments using a Y-maze showed that
      a primary pollinator of Protea species, the cetoniine beetle Atrichelaphinis
      tigrina, strongly preferred the scent of inflorescences of the beetle-pollinated
      Protea simplex over those of the bird-pollinated sympatric congener, Protea
      roupelliae. This study shows that a shift from passerine bird- to insect
      pollination can be associated with marked up-regulation and compositional changes
      in floral scent emissions.

PMID- 22999811
TI  - Efficacy and adverse events of antimuscarinics for treating overactive bladder:
      network meta-analyses.
AB  - CONTEXT: Millions of people worldwide experience overactive bladder (OAB), and
      antimuscarinics are the pharmacologic treatment of choice. Several conventional
      meta-analyses have been published, but they fail to quantify efficacy and adverse
      events across drugs, dosages, formulations, and pharmaceutical forms. OBJECTIVE:
      To perform two network meta-analyses summarizing the efficacy and adverse events
      of antimuscarinics in the treatment of OAB. EVIDENCE ACQUISITION: Medline and
      Scopus searches, previous systematic reviews, conference abstracts, book
      chapters, and the reference lists of relevant articles were searched. Trialists
      were contacted. Eligible studies were randomized trials that compared at least
      one antimuscarinic for treating OAB with placebo or with another antimuscarinic,
      and that reported efficacy and/or adverse event outcomes. Efficacy was assessed
      for six outcomes (perception of cure or improvement, urgency episodes per 24h,
      leakage episodes per 24h, urgency incontinence episodes per 24h, micturitions per
      24h, and nocturia episodes per 24h). Adverse events were assessed in seven
      categories according to the Common Terminology Criteria for Adverse Events.
      Across all outcomes, a summary efficacy and an adverse event score were computed.
      Two authors independently extracted data. EVIDENCE SYNTHESIS: For the comparison
      of the efficacy, 76 trials enrolling 38 662 patients were included; for adverse
      events, 90 trials enrolling 39 919 patients were included. In the subset of
      studies reporting on treatments and dosages as used in clinical practice, 40 mg/d
      trospium chloride, 100mg/g per day oxybutynin topical gel, and 4 mg/d
      fesoterodine had the best efficacy, while higher dosages of orally administered
      oxybutynin and propiverine had the least favorable relationship of efficacy and
      adverse events. CONCLUSIONS: This is the first study allowing trade-offs between
      efficacy and adverse events of various drugs and dosages in the treatment of
      patients with OAB. Differences among the various antimuscarinics call for
      careful, patient-centered management in which regimen changes should be
      considered.

PMID- 22999812
TI  - Controlling health care costs for prostate cancer.

PMID- 22999810
TI  - NF-kappaB and hypoxia: a double-edged sword in atherosclerosis.
AB  - This Commentary highlights the article by Fang et al, which describes novel mouse
      models of chronic intermittent hypoxia (CIH)-induced atherosclerosis, revealing
      that loss of the NF-kappaB p50 subunit increased atherosclerosis in the presence
      of CIH.

PMID- 22999813
TI  - Development and initial feasibility of an organizational measure of behavioral
      health integration in medical care settings.
AB  - In the advent of health care reform, models are sought to integrate behavioral
      health and routine medical care services. Historically, the behavioral health
      specialty has not itself been integrated, but instead bifurcated by substance use
      and mental health across treatment systems, care providers and even research.
      With the present opportunity to transform the health care delivery system, it is
      incumbent upon policymakers, researchers and clinicians to avoid repeating this
      historical error, and provide integrated behavioral health services in medical
      contexts. An organizational measure designed to assess this capacity is
      described: the Dual Diagnosis Capability in Health Care Settings (DDCHCS). The
      DDCHCS was used to assess a sample of federally-qualified health centers (N=13)
      on the degree of behavioral health integration. The measure was found to be
      feasible and sensitive to detecting variation in integrated behavioral health
      services capacity. Three of the 13 agencies were dual diagnosis capable, with
      significant variation in DDCHCS dimensions measuring staffing, treatment
      practices and program milieu. In general, mental health services were more
      integrated than substance use. Future research should consider a revised version
      of the measure, a larger and more representative sample, and linking
      organizational capacity with patient outcomes.

PMID- 22999814
TI  - Measuring client perceptions of motivational interviewing: factor analysis of the
      Client Evaluation of Motivational Interviewing scale.
AB  - Motivational interviewing (MI) is an intervention approach that has solid
      evidence of efficacy with substance use disorders. Research and training have
      benefitted from the development of observational measures to assess MI fidelity
      and competence. However, one untapped area of assessment is the client perception
      of the clinician use of MI. Client perceptions of MI have been found through
      qualitative interviews to relate to motivation to change, view of the therapist
      and safety of therapy. The Client Evaluation of MI (CEMI) scale was developed to
      assess client perception of clinician MI use. This study further evaluated the
      CEMI through exploratory and confirmatory factor analysis with a sample of 500
      individuals with dual diagnosis pre-discharge from an inpatient unit.
      Participants completed an MI based session prior to completing CEMIs. A two
      factor (relational and technical) model explained 51.1% of the cumulative
      variance and was supported through confirmatory factor analysis. Suggestions for
      revisions are provided as well as potential uses of the CEMI and future
      directions for research.

PMID- 22999815
TI  - Motivational interviewing to reduce hazardous drinking and drug use among
      depression patients.
AB  - This randomized study examined the efficacy of motivational interviewing (MI) to
      reduce substance use among adults with depression in outpatient psychiatry. The
      sample consisted of 104 participants ages 18 and over who reported hazardous
      drinking (three drinks or more per occasion), illegal drug use or misuse of
      prescription drugs in the prior 30 days, and who scored >= 15 on the Beck
      Depression Inventory-II (BDI-II). Participants were randomized to receive either
      three sessions of MI or printed literature about alcohol and drug use risks, as
      an adjunct to usual outpatient depression care, and completed telephone follow-up
      interviews at 3 and 6 months (93 and 99% of the baseline sample, respectively).
      Among participants reporting any hazardous drinking at baseline (n=73), MI
      treated participants were less likely than controls to report hazardous drinking
      at 3 months (60.0 vs. 81.8%, p=.043). MI is a promising intervention to reduce
      hazardous drinking among depression patients.

PMID- 22999816
TI  - [Voiding disorders in childhood: from diagnosis to treatment].
AB  - In voiding disorders in childhood, after a precise diagnosis, treatment can be
      provided. Aspecific hygienic and dietetic measures are the basis of care in all
      micturating disorders and frequently must be established to allow a precise
      diagnosis. In case of enuresis, restriction of beverage and diuretic foods is
      recommended in the evening. Other treatments for enuresis should be proposed to
      motivated children. In the polyuric form of enuresis, the treatment is
      desmopressin (DDAVP) and in the form with low bladder capacity, alarms or a
      combination of these 2 treatments. In dysfunctional voiding, after caring for the
      secondary causes, and depending on the characteristics of the disorder, the first
      step treatment is pelvic floor rehabilitation with or without anticholinergic
      therapy. Other medical treatments are used in a second step. Isolated urethral
      instability remains controversial.

PMID- 22999817
TI  - A randomized trial of intensive outpatient (IOP) vs. standard outpatient (OP)
      buprenorphine treatment for African Americans.
AB  - BACKGROUND: Buprenorphine is increasingly being used in community-based treatment
      programs, but little is known about the optimal level of psychosocial counseling
      in these settings. The aim of this study was to compare the effectiveness of OP
      and IOP level counseling when provided as part of buprenorphine treatment for
      opioid-dependent African Americans. METHODS: Participants were African American
      men and women starting buprenorphine treatment at one of two community-based
      clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at
      baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and
      cocaine dependence criteria, as well as additional outcomes of illicit opioid and
      cocaine use (urine test and self-report), criminal activity, retention in
      treatment, Quality of Life, Addiction Severity Index composite scores, and HIV
      risk behaviors. RESULTS: Participants assigned to OP received, on average, 3.67
      (SD=1.30)h of counseling per active week in treatment. IOP participants received
      an average of 5.23 (SD=1.68)h of counseling per active week (less than the
      anticipated 9h per week of counseling). Both groups showed substantial
      improvement over a 6-month period on nearly all measures considered. There were
      no significant differences between groups in meeting diagnostic criteria for
      opioid (p=.67) or cocaine dependence (p=.63). There were no significant between
      group differences on any of the other outcomes. A secondary analysis restricting
      the sample to participants meeting DSM-IV criteria for baseline cocaine
      dependence also revealed no significant between-group differences (all ps>.05).
      CONCLUSIONS: Buprenorphine patients receiving OP and IOP levels of care both show
      short-term improvements.

PMID- 22999818
TI  - Are novel combination therapies needed for chronic hepatitis B?
AB  - The treatment of chronic hepatitis B remains limited to monotherapy with
      pegInterferon-alpha or one of 5 different nucleoside analogues (NUC). While viral
      suppression can be achieved in approximately 95% of patients with new-generation
      NUCs, the rate of HBeAg seroconversion ranges from only 20% with NUCs to 30% with
      pegInterferon-alpha. HBsAg loss is achieved in only 10% of patients with both
      classes of drugs after a follow-up of 5years. Attempts to improve the response by
      administering two different NUCs or a combination of NUC and pegInterferon-alpha
      have been unsuccessful. This situation has led researchers to investigate a
      number of steps in the HBV replication cycle as potential targets for new
      antiviral drugs. Novel targets and compounds could readily be evaluated in in
      vitro and in vivo models of HBV infection. The addition of one or more new drugs
      to the current regimen should offer the prospect of markedly improving the
      response to therapy, reducing the future burden of drug resistance, cirrhosis and
      hepatocellular carcinoma.

PMID- 22999819
TI  - miR-125b regulates the proliferation of glioblastoma stem cells by targeting
      E2F2.
AB  - microRNAs (miRNAs) play important role in regulating cancer stem cell self
      renewal and differentiation, but the expression prolife of miRNAs in glioma stem
      cells (GSCs) has not been addressed. Here, we found that CD133 positive GSCs
      possess a unique miRNAs profile compared to CD133 negative glioblastoma cells.
      miR-125b, as one of neuronal miRNAs, is the most significantly down-regulated
      miRNAs and overexpression of miR-125b inhibits the proliferation of CD133
      positive GSCs and reduces the expression of "stem" marker. Furthermore, two
      binding sites for miR-125b are identified in the 3'UTR of E2F2 and overexpression
      of miR-125b in CD133 positive GSCs represses the endogenous level of E2F2
      protein. This study demonstrated that miR-125b plays important roles in
      regulating the proliferation of GSCs by directly targeting E2F2.

PMID- 22999820
TI  - Split-hand to diagnosis shot.

PMID- 22999821
TI  - Resonance between cortex and muscle: a determinant of motor precision?

PMID- 22999822
TI  - Kinesin family member 14 is a candidate prognostic marker for outcome of glioma
      patients.
AB  - BACKGROUND & AIM: Human kinesin superfamily proteins (KIFs) are a conserved class
      of microtubule-dependent molecular motor proteins with adenosine triphosphatase
      activity and motion characteristics. As a member of KIFs, KIF14 plays an
      important role in the regulation of cell cycle and mitotic progression.
      Deregulation of KIF14 has been found in several human malignancies and also has
      been demonstrated to be involved in tumor progression and related to patient
      survival. The aim of this study was to investigate the clinicopathological
      significance of KIF14 expression in glioma. METHODS: Real-time quantitative RT
      PCR assay was performed to detect KIF14 mRNA expression, and Western blot and
      immunohistochemistry analyses were performed to detect KIF14 protein expression
      in human gliomas and non-neoplastic brain tissues, respectively. Then, the
      association of KIF14 immunostaining with clinicopathological factors and
      prognosis of glioma patients was also statistically analyzed. RESULTS: KIF14 mRNA
      and protein expression were respectively increased 5.5- and 4.2-fold on average
      in glioma tissues relative to non-neoplastic brain tissues (both P < 0.001).
      Additionally, both KIF14 mRNA and protein expression increased with ascending
      pathological grade. Then, the high KIF14 immunostaining in glioma tissues was
      significantly associated with advanced pathological grade (P = 0.008), low
      Karnofsky performance score (KPS) (P = 0.02), high mitotic index (P = 0.005) and
      Ki-67 index (P = 0.008). Furthermore, both univariate and multivariate Cox
      regression analyses determined that KIF14 overexpression effectively predicted
      decreased overall survival in patients with gliomas. CONCLUSIONS: These findings
      offer the first convinced evidence that KIF14 expression in gliomas is tumor
      specific and increased in more aggressive tumors. KIF14 might function as a
      candidate prognostic marker for human gliomas.

PMID- 22999823
TI  - Behavioral indices of breeding readiness in female European starlings correlate
      with immunolabeling for catecholamine markers in brain areas involved in sexual
      motivation.
AB  - In seasonally-breeding songbirds, lengthening photoperiod, increases in estradiol
      and exposure to male courtship facilitate breeding behavior in females in spring.
      However, there is extreme variability in the extent to which spring-condition
      females are attracted by male courtship or engage in nesting behavior. Here we
      explore possible links between catecholamines and individual differences in
      behaviors indicative of breeding readiness. Female European starlings were placed
      in conditions typical of the breeding season (spring-like) or the non-breeding
      season (fall-like). Although many females examined nesting locations, only a
      subset of spring-like females occupied nest sites. Labeling for dopamine-beta
      hydroxylase (DBH; the enzyme involved in norepinephrine synthesis) in the
      ventromedial nucleus of the hypothalamus (VMH) was densest in females that
      acquired nest sites compared to spring-like females without nest sites or fall
      like females. Within the group of spring-like females, nesting behaviors
      correlated positively with DBH labeling in VMH. Females with nest sites had the
      lowest density of DBH labeling in the ventral tegmental area, and labeling
      correlated negatively with spring-like female nesting behaviors. Labeling for
      tyrosine hydroxylase (TH; the rate limiting enzyme for catecholamine synthesis)
      in putative nucleus accumbens was lowest in spring-like females without nest
      sites, and labeling correlated positively with nesting behavior in spring-like
      females. TH labeling density in the medial preoptic nucleus was highest in fall
      like females, but a trend was observed for a positive correlation between TH
      labeling and spring-like female nesting behaviors. These results link distinct
      patterns of catecholamine activity in brain regions implicated in sexual
      motivation to female breeding readiness.

PMID- 22999824
TI  - The preventive effect of statin therapy on new-onset and recurrent atrial
      fibrillation in patients not undergoing invasive cardiac interventions: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Previous meta-analyses suggest that pre-procedural use of statin
      therapy may reduce atrial fibrillation (AF) following invasive cardiac
      interventions (coronary artery by-pass grafting and percutaneous coronary
      intervention). However, the current evidence on the benefit of statins unrelated
      to invasive cardiac interventions has not been clarified systematically. METHODS:
      Through a systematic literature search, trials examining the effect of statin
      therapy on AF were selected. Trials using statins before any percutaneous or
      surgical cardiac interventions were excluded. RESULTS: The search identified 11
      randomized and 16 observational eligible studies, totaling 106,640 patients
      receiving statin therapy and 129,305 serving as controls. Fourteen studies
      investigated the effect of statins on new-onset AF, 13 studies investigated the
      effect of statins on recurrent AF and one in both new-onset and recurrent AF. In
      the statin versus control group the mean age was 60.7 +/- 8.3 versus 68.6 +/- 6.2
      years and females comprised 8.4% versus 10.3%. Statin therapy was associated with
      significant reduction of AF (Risk ratio (RR): 0.81 [95% confidence interval (CI):
      0.80-0.83], p<0.001) combining all studies. Assessing exclusively randomized
      trials, statin therapy showed no significant risk reduction (RR: 0.97 [95%CI:
      0.90-1.05], p=0.509), heterogeneity p>0.05. Assessing exclusively observational
      studies the risk reduction of new-onset AF was 12% (RR: 0.88 [95%CI: 0.85-0.91],
      p<0.001) and recurrent AF 15% (RR: 0.85 [95%CI: 0.80-0.90], p<0.001),
      heterogeneity p<0.001. CONCLUSION: The hitherto published randomized clinical
      trials do not support a beneficial effect of statins on AF in patients not
      undergoing invasive cardiac interventions. This is in contrast to the results of
      observational and interventional studies.

PMID- 22999825
TI  - Bioreporters and biosensors for arsenic detection. Biotechnological solutions for
      a world-wide pollution problem.
AB  - A wide variety of whole cell bioreporter and biosensor assays for arsenic
      detection has been developed over the past decade. The assays permit flexible
      detection instrumentation while maintaining excellent method of detection limits
      in the environmentally relevant range of 10-50 MUg arsenite per L and below. New
      emerging trends focus on genetic rewiring of reporter cells and/or integration
      into microdevices for more optimal detection. A number of case studies have shown
      realistic field applicability of bioreporter assays.

PMID- 22999826
TI  - Engineering the antioxidative properties of lactic acid bacteria for improving
      its robustness.
AB  - Lactic acid bacteria (LAB) that are widely used in the food fermentations often
      encounter various environmental stresses during manufacturing and application.
      Improving the antioxidative properties of LAB was found to be an effective
      approach for increasing their general robustness. Here we review the recent
      progress of engineering the antioxidative properties of LAB, with focus on
      engineering the thiol compounds production. Engineering of the enzymes involved
      in oxidative stress resistance are also discussed. To further improve the
      industrial relevant robustness, engineering LAB at a higher control level is
      expected.

PMID- 22999827
TI  - In situ microbial metabolism of aromatic-hydrocarbon environmental pollutants.
AB  - Microbial processes that eliminate organic environmental contamination are
      important. Progress in the biotechnology of biodegradation relies upon the
      underlying sciences of environmental microbiology and analytical geochemistry.
      Recent key discoveries advancing knowledge of biodegradation (in general) and the
      aromatic-hydrocarbon biodegradation (in particular) have relied upon
      characterization of microorganisms: pure-culture isolates, laboratory enrichment
      cultures, and in contaminated field sites. New analytical and molecular tools
      (ranging from sequencing the DNA of biodegrading microorganisms to assessing
      changes in the isotopic ratios of 13C to 12C and 2H to 1H in contaminant pools in
      field sites) have deepened our insights into the mechanisms (how), the occurrence
      (what), and the identity (who) of active players that effect biodegradation of
      organic environmental pollutants.

PMID- 22999828
TI  - Metabolomic investigations of anaerobic hydrocarbon-impacted environments.
AB  - Metabolomics is a powerful tool for the assessment of expressed (in vivo or in
      situ) biological processes. Metabolite profiling is often employed during field
      investigations of hydrocarbon-laden environments for the purpose(s) of
      determining the extent of intrinsic or enhanced natural attenuation of
      contaminants, developing remediation strategies, and/or gaining a better
      understanding of microbial processes. During the last twenty-five years, the
      elucidation of anaerobic biodegradation pathways has not only provided metabolic
      and molecular biomarkers for environmental assessments of anaerobic hydrocarbon
      metabolism, but also an avenue for integrative field studies. The combination of
      metabolomics with compound-specific isotope analysis, molecular surveys and/or
      microcosm studies has demonstrated the need for multiple assessment methods for
      better resolution of in situ microbial activity.

PMID- 22999829
TI  - Nonalcoholic fatty liver in children and adolescents: an overview.
AB  - Nonalcoholic fatty liver disease is rapidly becoming one of the most common liver
      diseases in the pediatric population in industrialized countries because of the
      growing prevalence of obesity and overweight. For this reason, there is a keen
      and broad interest among researchers to identify new diagnostic noninvasive tools
      and novel treatment modalities for this condition. Unfortunately, to date, liver
      biopsy remains the imperfect gold standard for diagnosis. In addition, available
      noninvasive markers are not fully satisfactory for the diagnosis of fatty liver.
      Although in recent years many pharmacological agents, on the basis of
      pathogenetic mechanism of the disease, have been attempted, to date, the
      guidelines for the management of fatty liver are still lacking. Establishing
      effective therapeutic strategies to treat the disease represents the challenge
      for pediatric hepatologists in the near future. In this article, we briefly
      review the current knowledge and ideas concerning pediatric nonalcoholic fatty
      liver disease, and discuss the new perspective therapies.

PMID- 22999830
TI  - Impact of maternal HIV health: a 12-year study of children in the Parents And
      Children Coping Together project.
AB  - PURPOSE: The purpose of this 12-year longitudinal study was to assess the effects
      of maternal HIV/AIDS on child/adolescent well-being and behavioral outcomes,
      extending an earlier published account. METHODS: Interviews were conducted with
      66 pairs of healthy children and their mothers living with HIV/AIDS, who are
      participants in the Parents And children Coping Together (PACT) project begun in
      1997. All study participants were English or Spanish speaking. About half (48.5%)
      of the youth were female. Maternal health status (e.g., viral load biomedical
      marker, illness symptoms, physical functioning, and depression) and
      child/adolescent outcomes (e.g., depression, anxiety/worry, aggression, and self
      concept) were assessed over 16 time points. RESULTS: Using growth curve modeling,
      results show a negative effect of maternal health status on child/adolescent
      outcomes, including child/adolescent depression, anxiety/worry, aggression, and
      self-concept. Interaction effects within the growth models suggest younger
      children are more impacted by poor maternal health than are older
      children/adolescents. CONCLUSIONS: This is the first study to follow a cohort of
      children of mothers living with HIV/AIDS over such an extended age range, through
      late adolescence/early adulthood, to determine the impact of maternal health
      status throughout the entire developmental period.

PMID- 22999831
TI  - Knowledge and likelihood to recommend intrauterine devices for adolescents among
      school-based health center providers.
AB  - PURPOSE: The American College of Obstetricians and Gynecologists and the Centers
      for Disease Control and Prevention recommend intrauterine devices (IUDs) as safe
      and highly effective contraceptives for adolescents. Nevertheless, many U.S.
      providers do not recommend or provide IUDs to adolescents-a population at high
      risk for unintended pregnancy. The purpose of this study was to identify barriers
      to IUD provision for adolescents. METHODS: A 36-item self-administered survey of
      knowledge and attitudes regarding IUDs was completed by 162 staff of New York
      City school-based health centers, including 69 clinicians (e.g., pediatricians
      and nurse practitioners) and 93 nonclinicians (e.g., social workers and health
      educators). RESULTS: Half (55%) of all respondents would be likely to recommend
      an IUD to a patient under age 20 years. Respondents were less likely to recommend
      an IUD for patients with history of recent STD (31%), remote pelvic inflammatory
      disease (37%), and patients not in a monogamous relationship (38%). Whereas 77%
      of respondents indicated that IUDs are safe for adolescents, 18% of those
      respondents would be unlikely to recommend an IUD to a patient under age 20
      years. While 86% of respondents knew that IUDs can be used in nulliparous women,
      25% of those respondents would be unlikely to recommend an IUD to a patient who
      has never been pregnant. Additionally, 61% believed that counseling patients
      about IUDs would take more time than other methods. CONCLUSIONS: Misinformation
      about risks associated with IUDs and beliefs about patient eligibility may
      present barriers to provision. Apparent contradictions between knowledge and
      likelihood to recommend IUDs warrant further study.

PMID- 22999832
TI  - Associations between community attachments and adolescent substance use in
      nationally representative samples.
AB  - PURPOSE: Social capital and social attachment theories of substance use argue
      that positive bonds to society and the conventional values they promote deter
      adolescents from substance use. Using nationally representative samples of U.S.
      high school seniors, we hypothesized that adolescents' community attachments,
      measured by social trust, social responsibility, and religiosity, would be
      negatively associated with lifetime and 30-day substance use. METHOD: We used
      repeated cross-sectional nationally representative high school senior data from
      1976 to 2008 Monitoring the Future Study cohorts (weighted N = 64,246; 51.6%
      female). Participation rate ranged from 77% to 86% across years. A series of
      multiple linear and logistic regressions examined unique associations of
      adolescents' social trust, social responsibility, and religiosity with lifetime
      and 30-day use of cigarettes, alcohol, marijuana, hallucinogens, cocaine,
      amphetamines, barbiturates, tranquilizers, and narcotics. Models controlled for
      gender, race, college aspirations, high school grades, parents' education, and
      survey year. RESULTS: Social trust, social responsibility, and religiosity showed
      independent negative associations with use of cigarettes, alcohol, marijuana, and
      six other types of drugs. After accounting for controls, community attachments
      related to lower lifetime and past 30-day use. Associations were consistent
      across measures, except social responsibility was not associated with binge
      drinking or lifetime illicit drugs besides marijuana. CONCLUSIONS: Study
      strengths included nationally representative samples, diverse substance use
      measures, and inclusion of controls. We extend theory by suggesting that distinct
      aspects of adolescents' community attachments uniquely relate to lower substance
      use. Results suggest potential public health benefits of integrating promotion of
      community attachments with substance use prevention.

PMID- 22999833
TI  - Consequences of sex education on teen and young adult sexual behaviors and
      outcomes.
AB  - PURPOSE: This study examined whether formal sex education is associated with
      sexual health behaviors and outcomes using recent nationally representative
      survey data. METHODS: Data used were from 4,691 male and female individuals aged
      15-24 years from the 2006-2008 National Survey of Family Growth. Weighted
      bivariate and multivariate analyses were conducted by gender, estimating the
      associations of sex education by type (only abstinence, abstinence and birth
      control, or neither) before first sexual intercourse, and sexual behaviors and
      outcomes. RESULTS: Receipt of sex education, regardless of type, was associated
      with delays in first sex for both genders, as compared with receiving no sex
      education. Respondents receiving instruction about abstinence and birth control
      were significantly more likely at first sex to use any contraception (odds ratio
      [OR] = 1.73, females; OR = 1.91, males) or a condom (OR = 1.69, females; OR =
      1.90, males), and less likely to have an age-discrepant partner (OR = .67,
      females; OR = .48, males). Receipt of only abstinence education was not
      statistically distinguishable in most models from receipt of either both or
      neither topics. Among female subjects, condom use at first sex was significantly
      more likely among those receiving instruction in both topics as compared with
      only abstinence education. The associations between sex education and all longer
      term outcomes were mediated by older age at first sex. CONCLUSIONS: Sex education
      about abstinence and birth control was associated with healthier sexual behaviors
      and outcomes as compared with no instruction. The protective influence of sex
      education is not limited to if or when to have sex, but extends to issues of
      contraception, partner selection, and reproductive health outcomes.

PMID- 22999834
TI  - Experience of low mood and suicidal behaviors among adolescents in Vietnam:
      findings from two national population-based surveys.
AB  - PURPOSE: To date, no population-based data about experiences of low mood and
      suicidal behaviors among adolescents in Vietnam have been published in the
      English peer-reviewed literature. The aim was to establish the prevalence of self
      reported symptoms of low mood, acts of self-harm, and suicidal thoughts and their
      correlates among adolescents from two national population-based surveys, Survey
      Assessment of Vietnamese Youth (SAVY) I (2003-2004) and II (2009-2010). METHODS:
      Data from the subset of participants aged 14-19 years from the two structured
      SAVYs were analyzed. Descriptive and bivariate statistics were used to test for
      between-group comparisons. Multiple logistic regressions were performed to
      determine factors associated with low mood and suicidal ideation. A weighting
      factor was used in all analyses. RESULTS: Prevalence of experiences of low mood
      was 34.06% in SAVY I and 37.34% in SAVY II; prevalence of suicidal behaviors was
      5.28% (SAVY I) and 12.21% (SAVY II). Significant risk factors were being female,
      an ethnic minority, illiterate, or exposed to violence; perceiving study load as
      too heavy; following a religion other than Buddhism; or living in wealthier
      families. Better family cohesion protected adolescents from these unfavorable
      outcomes. Alcohol use co-occurred significantly with experiences of low mood and
      suicidal behaviors. CONCLUSIONS: Self-reported lifetime experiences of low mood
      are common among Vietnamese adolescents, with signs of an increasing trend.
      Suicidal behaviors are less prevalent than in other settings but are also
      increasing. Further research is warranted to elucidate these findings and to
      inform interventions to optimize the mental health of adolescents in Vietnam.

PMID- 22999835
TI  - Assessing the effects of Families for Safe Dates, a family-based teen dating
      abuse prevention program.
AB  - PURPOSE: To examine the effects of a family-based teen dating abuse prevention
      program, Families for Safe Dates, primarily on outcomes related to testing the
      conceptual underpinnings of the program including (1) factors motivating and
      facilitating caregiver engagement in teen dating abuse prevention activities, and
      2) risk factors for teen dating abuse, and secondarily on dating abuse behaviors.
      METHODS: Families were recruited nationwide using listed telephone numbers.
      Caregivers and teens completed baseline and 3-month follow-up telephone
      interviews (n = 324). Families randomly allocated to treatment condition received
      the Families for Safe Dates program including six mailed activity booklets
      followed-up by health educator telephone calls. RESULTS: There were significant
      (<.05) treatment effects in hypothesized directions on most of the factors
      motivating and facilitating caregiver engagement in teen dating abuse prevention
      activities including caregiver perceived severity of dating abuse, response
      efficacy for preventing dating abuse, self-efficacy for talking about dating
      abuse, knowledge of dating abuse, acceptance of dating abuse, communication
      skills with the teen, and belief in the importance of involvement in their male
      (but not female) teen's dating. The latter effect was the only one moderated by
      sex of the teen. The targeted risk factor affected by the program was teen
      acceptance of dating abuse. Treatment was also significantly associated with less
      physical dating abuse victimization. CONCLUSIONS: Modifications to the program
      are warranted, but overall, the findings are very favorable for the first family
      based teen dating abuse prevention program to be evaluated.

PMID- 22999836
TI  - Caregiver and adolescent mental health in Ethiopian Kunama refugees participating
      in an emergency education program.
AB  - PURPOSE: To examine the role of caregiver mental health and risk and protective
      factors in influencing levels of internalizing and externalizing emotional and
      behavioral symptoms over time among a sample of refugee adolescents. METHODS:
      Prospective study of 153 Kunama refugee adolescents receiving an emergency
      education intervention while living in a camp in Ethiopia. Surveys were collected
      in 2001 (T1) and 2002 (T2). Adolescent and caregiver mental health were assessed
      using a Kunamenga adaptation of the Youth Self Report; caregiver mental health
      was assessed using the Hopkins Symptom Checklist-25. Attitudes toward education,
      satisfaction with education programming, socioeconomic status, and perceptions of
      access to services were also explored as variables potentially influencing
      adolescent mental health at follow-up. RESULTS: Caregiver distress was
      significantly associated with youth externalizing behavior symptoms (beta = 8.34,
      p < .001) and internalizing symptoms (beta = 4.02, p < .05). Caregiver perceived
      access to services had a protective effect on externalizing behaviors (beta = 
      7.54, p < .05) and internalizing behaviors (beta = -13.67, p < .001). Higher
      socioeconomic status (beta = -1.47, p < .05) had a protective effect on
      internalizing symptoms. In terms of modifying effects, among youth with
      distressed caregivers, those who were satisfied with the International Rescue
      Committee education intervention had a lower internalizing score (beta = -6.34, p
      < .001) compared with those who were not satisfied with the program. CONCLUSIONS:
      This study presents a rare prospective investigation of caregiver-adolescent
      mental health during an active refugee displacement. Results suggest that
      programs targeting mental health in refugee children should consider children
      within the larger family system, including caregiver influence on child and
      adolescent mental health adjustment over time.

PMID- 22999837
TI  - The longitudinal impact of exposure to violence on cortisol reactivity in
      adolescents.
AB  - PURPOSE: The purpose of this report is to examine the effect of exposure to
      violence (ETV) on cortisol reactivity (CR) in children with no identified serious
      mental health problems or reports of maltreatment. ETV was hypothesized to
      influence development of the stress system in this sample of youth as has been
      demonstrated in maltreated youth. METHODS: The sample consisted of 124
      adolescents aged 8-13 years. Data were collected at two waves of measurement 12
      months apart. ETV was operationalized as the number of different violent events
      each child was exposed to as a witness or victim. CR was evaluated in relation to
      the Trier Social Stress Test for Children. RESULTS: ETV occurring during the 12
      months before the first assessment was predictive of CR 12 months later in boys,
      even after controlling for age and Time 1 symptoms of psychopathology, CR, and
      lifetime ETV. Lifetime ETV at Time 1 was positively correlated with symptoms of
      major depressive disorder and generalized anxiety disorder in both sexes.
      CONCLUSIONS: The unique aspect of the current findings is that typically research
      studying the effects of ETV is conducted with a clinical or maltreated sample.
      The findings show that recent ETV has an effect on reactions to a laboratory
      stressor and has longer-term negative mental health consequences. Further study
      is needed to determine whether these effects are enduring or a shorter-term
      adaptive response to ETV.

PMID- 22999838
TI  - Role of birth weight and postnatal growth on pulse wave velocity in teenagers.
AB  - PURPOSE: Low birth weight and accelerated postnatal growth appear to play a
      significant role in the pathogenesis of hypertension and cardiovascular disease
      in adulthood. The aim of the present study was to characterize the factors
      determining pulse wave velocity (PWV) in teenagers and, in particular, to verify
      the relationship with birth weight, postnatal growth, timing of adiposity
      rebound, lifestyle, and hemodynamic parameters. METHODS: Carotid-femoral and
      carotid-radial pulse wave velocities of 558 healthy teenagers (age range: 16.2
      19.9 years) were determined by means of a PulsePen tonometer. Birth weight and
      gestational age were obtained from obstetrical records, and data regarding
      postnatal growth were obtained from pediatric clinical records. RESULTS: No
      change in aortic PWV was found in association with birth weight, postnatal
      growth, and timing of adiposity rebound. However, the study showed a strong
      association between accelerated growth from 0 to 12 months and carotid-radial PWV
      (trend: p = .02). Subjects with birth weight values <2,500 g showed higher values
      of upper limb PWV (p < .05) and higher values of diastolic and mean arterial
      pressure (p < .05). Stepwise regression analysis revealed that mean arterial
      pressure, age, and height were the main independent factors determining aortic
      PWV in this young population. CONCLUSIONS: These results suggest that there is no
      linear correlation between birth weight and hemodynamic parameters in teenagers;
      however, subjects characterized by very low birth weight and accelerated
      postnatal weight gain appear to demonstrate increased upper limb PWV and
      diastolic and mean arterial pressure values.

PMID- 22999839
TI  - Helpful or harmful? An examination of viewers' responses to nonsuicidal self
      injury videos on YouTube.
AB  - PURPOSE: To examine viewers' comment responses to nonsuicidal self-injury (NSSI)
      YouTube videos to determine the potential risks (e.g., NSSI continuation) and
      benefits (e.g., recovery-oriented social support) of the videos. METHODS:
      Viewers' comments from the 100 most-viewed NSSI videos on YouTube were examined
      using two coding rubrics, one for the global nature of comments and one for
      recovery-oriented themes. Both rubrics were developed using an inductive (bottom
      up) approach and had high coding inter-rater reliability (exceeding .80 in all
      cases). For the global nature of comments, 869 randomly selected comments were
      evaluated using the rubric, which included 8 coding categories and 22
      subcategories. For the examination of recovery-oriented themes, self-disclosure
      comments (n = 377) were evaluated for nature of recovery statements. RESULTS:
      Results revealed that the most frequent comments were self-disclosure comments in
      which individuals shared their own NSSI experiences (38.39%), followed by
      feedback for the video uploader, including admiration of the video quality
      (21.95%) or message (17.01%), and admiration for the uploader (15.40%) or
      encouragement to the video uploader (11.15%). Evaluation of the common self
      disclosure comments for recovery-oriented content revealed that the majority did
      not mention recovery at all (42.89%) and indicated that they were still self
      injuring (34.00%). Positive recovery statements were uncommon. CONCLUSIONS:
      Results suggest that viewers' responses to videos may maintain the behavior (by
      sharing their own self-injury experiences) and rarely encourage or mention
      recovery. It is evident that sharing their own experience online is a strong
      motivator for viewers of NSSI YouTube videos.

PMID- 22999840
TI  - Social network and individual correlates of sexual risk behavior among homeless
      young men who have sex with men.
AB  - PURPOSE: There is growing interest in network-based interventions to reduce HIV
      sexual risk behavior among both homeless youth and men who have sex with men. The
      goal of this study was to better understand the social network and individual
      correlates of sexual risk behavior among homeless young men who have sex with men
      (YMSM) to inform these HIV prevention efforts. METHODS: A multistage sampling
      design was used to recruit a probability sample of 121 homeless YMSM (ages: 16-24
      years) from shelters, drop-in centers, and street venues in Los Angeles County.
      Face-to-face interviews were conducted. Because of the different distributions of
      the three outcome variables, three distinct regression models were needed:
      ordinal logistic regression for unprotected sex, zero-truncated Poisson
      regression for number of sex partners, and logistic regression for any sex trade.
      RESULTS: Homeless YMSM were less likely to engage in unprotected sex and had
      fewer sex partners if their networks included platonic ties to peers who
      regularly attended school, and had fewer sex partners if most of their network
      members were not heavy drinkers. Most other aspects of network composition were
      unrelated to sexual risk behavior. Individual predictors of sexual risk behavior
      included older age, Hispanic ethnicity, lower education, depressive symptoms,
      less positive condom attitudes, and sleeping outdoors because of nowhere else to
      stay. CONCLUSIONS: HIV prevention programs for homeless YMSM may warrant a
      multipronged approach that helps these youth strengthen their ties to prosocial
      peers, develop more positive condom attitudes, and access needed mental health
      and housing services.

PMID- 22999841
TI  - Attention-deficit/hyperactivity disorder subtype differentially predicts smoking
      expectancies in adolescents.
AB  - PURPOSE: Attention deficit hyperactivity disorder (ADHD) is an established risk
      factor for smoking; however, no studies have considered whether precursors to
      smoking behavior differ among adolescents with ADHD. Smoking expectancies are
      beliefs about the potential consequences of smoking, and they develop before
      smoking initiation. ADHD characteristics may contribute to the formation of
      expectancies and eventual smoking behavior. We evaluated whether clinical levels
      of ADHD subtypes differentially predicted smoking expectancies. METHODS:
      Adolescents (n = 221; age mean = 12.67 years) completed the Smoking Expectancy
      Scale for Adolescents, answered standardized questions about their smoking
      behavior, and provided expired breath samples to verify never-smoking status.
      Parents completed the Conners' Parent Rating Scale for ADHD symptoms of
      inattention and hyperactivity/impulsivity. RESULTS: Adolescents with clinical
      levels of inattention were significantly less likely to endorse negative
      consequences, including Expected Costs (odds ratio [OR] = .16), Appearance
      Presentation Costs (OR = .29), Social Costs (OR = .19), Health Costs (OR = .21),
      and Addiction Costs (OR = .39). Inattentive female adolescents were significantly
      more likely to endorse Weight Control as a consequence. Adolescents with clinical
      levels of hyperactivity/impulsivity were more likely to endorse positive
      consequences, including Expected Benefits (OR = 5.31), Affect Control (OR =
      2.60), and Boredom Reduction (OR = 3.14); they were less likely to endorse Social
      Costs (OR = .27). CONCLUSIONS: ADHD subtype differentially predicted smoking
      expectancies. Adolescents with ADHD may be more vulnerable to developing pro
      smoking expectancies due to subtype-related deficits in neurocognitive
      processing. These findings have potential implications for developing targeted
      smoking prevention programs.

PMID- 22999842
TI  - Accuracy and trust of self-testing for bacterial vaginosis.
AB  - PURPOSE: Two point-of-care tests are available to detect bacterial vaginosis
      (BV), a common vaginal condition. This study aimed to (1) compare the accuracy of
      two self-performed BV tests with clinician-performed BV tests and with clinical
      diagnosis of BV; and (2) compare trust of results for self-performed BV testing
      with clinician-performed BV testing. METHODS: Participants (14-22 years old) in a
      study assessing self-testing for Trichomonas vaginalis were also asked to perform
      a self-test for BV (using a pH or sialidase test). Results were compared with
      clinician-performed tests and with clinical diagnosis of BV (defined by modified
      Amsel criteria). A two-item subscale from a larger acceptability scale was used
      to assess trust at baseline, after testing, and after discussion of results.
      RESULTS: All 131 women performed self-BV testing correctly. Agreement between
      self- and clinician-performed tests was good (kappa: .5-.7) Compared with
      clinical diagnosis of BV, self-pH was 73% sensitive and 67% specific, and self
      sialidase was 40% sensitive and 90% specific. Trust in self-performed BV testing
      was lower than trust in clinician-performed BV testing at baseline, but increased
      after testing and discussion of results. CONCLUSIONS: Young women can perform
      self-tests for BV with reasonable accuracy, which could increase testing when
      pelvic examinations are not feasible. Trust in self-testing increased after
      experience and after discussion of test results. Although the pH test is
      available over the counter, young women may continue to rely on clinicians for
      testing.

PMID- 22999843
TI  - Timing of surgery after neoadjuvant long-course chemoradiotherapy in the
      management of locally advanced rectal cancer.

PMID- 22999844
TI  - The Escherichia coli adherence factor plasmid of enteropathogenic Escherichia
      coli causes a global decrease in ubiquitylated host cell proteins by decreasing
      ubiquitin E1 enzyme expression through host aspartyl proteases.
AB  - Ubiquitylation is a widespread post-translational global regulatory system that
      is essential for the proper functioning of various cellular events. Recent
      studies have shown that certain types of Escherichia coli can exploit specific
      aspects of the ubiquitylation system to influence downstream targets. Despite
      these findings, examination of the effects pathogenic E. coli have on the overall
      host ubiquitylation system remain unexplored. To study the impact that pathogenic
      E. coli have on the ubiquitylation levels of host proteins during infections, we
      analyzed the entire ubiquitylation system during enteropathogenic E. coli
      infections of cultured cells. We found that these microbes caused a dramatic
      decrease in ubiquitylated host proteins during these infections. This occurred
      with a concomitant reduction in the expression of essential E1 activating enzymes
      in the host, which are integral for the initiation of the ubiquitylation cascade.
      Control of host E1 enzyme levels was dependent on the E. coli adherence factor
      plasmid which acted on host aspartyl proteases within enteropathogenic E. coli.
      Hijacking of the ubiquitylation system did not require the plasmid-encoded
      regulator or bundle forming pilus expression, as enteropathogenic E. coli mutated
      in those factors did not revert the ubiquitylation of host proteins or the
      abundance of E1 enzyme proteins to uninfected levels. Our work shows that E. coli
      have developed strategies to usurp post-translational systems by targeting
      crucial enzymes. The ability of enteropathogenic E. coli to inactivate host
      protein ubiquitylation could enable more efficient effector protein
      functionality, providing increased bacterial control of host cells during
      enteropathogenic E. coli pathogenesis.

PMID- 22999845
TI  - Accurate coracoid graft placement through use of a drill guide for the Latarjet
      procedure.
AB  - BACKGROUND: The Latarjet procedure has widely become the preferred treatment
      option for recurrent anterior glenohumeral instability in the presence of glenoid
      bone loss. The success of this procedure is largely dependent on accurate
      placement of the coracoid bone graft relative to the glenoid margin. With
      malpositioning of the coracoid graft, complications can arise, such as recurrent
      instability if placed too medially or impingement and subsequent early
      degenerative changes if positioned too laterally. To increase the accuracy and
      reproducibility of coracoid graft placement, we developed a simple and efficient
      drill guide that assists in accurate and safe positioning of the graft against
      the anterior glenoid to provide a congruent articular surface. MATERIALS AND
      METHODS: A new drill guide was used in 12 consecutive open Latarjet procedures.
      Accuracy of placement of the graft with respect to the anterior glenoid rim was
      assessed using postoperative computed tomography imaging. RESULTS: Accurate graft
      placement with a distance between the glenoid and the graft surface of less than
      1 mm was obtained in all 12 interventions. The mean angulation of the screws
      relative to the glenoid face was 4.3 degrees  (range, 1 degrees -7 degrees ). All
      screw heads were positioned medial to the articular edge of the graft, and the
      distance was always greater than 3 mm. CONCLUSIONS: The use of a simple drill
      guide allows safe and accurate graft placement during an open Latarjet procedure.

PMID- 22999846
TI  - Regional variations in radial head bone volume and density: implications for
      fracture patterns and fixation.
AB  - BACKGROUND: Fractures of the radial head are common with most partial articular
      fractures resulting in an anterolateral fragment. The exact mechanism of radial
      head fracture is unknown; however, forces transmitted and variations in local
      bone density are believed important. This study quantifies the regional
      variations in bone density and volume of the radial head to better understand the
      pathomechanics of fracture patterns. METHODS: Computer tomography scan data of 18
      cadaver elbows were imported into imaging analysis software. The radial head was
      divided into quadrants based on neutral forearm rotation. Bone density and volume
      were calculated and compared between quadrants. RESULTS: The regional densities
      of bone expressed in Hounsfield units (HU) were posteromedial quadrant (PM) 496
      +/- 87 HU, anteromedial quadrant (AM) 443 +/- 72 HU, anterolateral quadrant (AL)
      409 +/- 60 HU, and posterolateral quadrant (PL) 406 +/- 57 HU. The volume of bone
      in descending order was PM 1138 +/- 179 mm(3), PL 1013 +/- 213 mm(3), AM 1010 +/-
      210 mm(3), and AL 938 +/- 175 mm(3). The PM quadrant was significantly denser
      than the AM, AL, and PL quadrants, (P = .001) and the AM quadrant was
      significantly denser than the AL and PL quadrants (P = .006 and .009). The PM
      quadrant had significantly more bone volume when compared to the AM, AL, and PL
      (P = .001). The AM and PL quadrants had significantly greater bone volume
      compared to AL quadrant (P = .023 and .018, respectively). CONCLUSION: Radial
      head bone volume and density is highest in the posteromedial quadrant and lowest
      in the anterolateral quadrant where fractures occur more frequently.

PMID- 22999847
TI  - Efficacies of corticosteroid injection at different sites of the shoulder for the
      treatment of adhesive capsulitis.
AB  - BACKGROUND: A corticosteroid injection in the glenohumeral joint conducted
      blindly is technically demanding with a low rate of accuracy despite satisfactory
      clinical outcomes in the treatment for adhesive capsulitis. This study
      prospectively compared the clinical outcomes of patients with idiopathic adhesive
      capsulitis treated by a single corticosteroid injection in different locations of
      the shoulder. MATERIALS AND METHODS: We randomly assigned 191 patients with
      adhesive capsulitis to 1 of 4 groups based on corticosteroid injection location:
      group I, subacromial; group II, intra-articular; group III, intra-articular
      combined with subacromial space; and group IV, medication. Pain relief and
      patient satisfaction were assessed with a visual analog scale and functional
      outcomes were evaluated with the American Shoulder and Elbow Surgeons score up to
      24 weeks after treatment. RESULTS: Patients treated with corticosteroids achieved
      faster pain relief and had greater satisfaction levels than patients in group IV
      during the 16 weeks after treatment. However, no significant difference in pain
      scores was observed among the 4 groups at 24-week follow-up visits (P = .670).
      Shoulder motion and function improved in all groups at final follow-up. However,
      shoulder motion in the injection groups recovered faster than that in group IV.
      At 24 weeks after treatment, no significant differences in shoulder motion or
      functional outcomes were found among the 4 groups (P = .117). CONCLUSIONS: The
      efficacy of a single corticosteroid injection was not found to be related to the
      site of injection. However, a single corticosteroid injection provided faster
      pain relief, a higher level of patient satisfaction, and an earlier improvement
      in shoulder motion and function than medication in patients with adhesive
      capsulitis.

PMID- 22999848
TI  - A biomechanical analysis of initial fixation options for porous-tantalum-backed
      glenoid components.
AB  - BACKGROUND: Porous-tantalum (PT)-backed glenoid components have recently been
      developed to improve fixation and minimize the incidence of glenoid component
      loosening, which remains a key limiting factor in long-term survival in total
      shoulder arthroplasty. PT-backed glenoids promote bony ingrowth as a method of
      preventing glenoid loosening at the prosthesis-glenoid interface. The use of
      polymethyl-methacrylate (PMMA) cement for initial fixation may prevent
      osteointegration due to mechanical occlusion of the porous surface and the
      nonosteoconductive properties of PMMA. This study aims to investigate alternative
      fixation methods of PT-backed glenoids in a biomechanical investigation.
      MATERIALS AND METHODS: Nine PT-backed monoblock glenoid components were implanted
      in a polyurethane bone substitute using either press-fit, PMMA cement, or calcium
      phosphate cement techniques. A control group of 3 all-polyethylene pegged glenoid
      components was implanted with PMMA. Glenoid and humeral head components were
      fixed to a biomechanical testing machine for testing according to ASTM Standard F
      2028. The humeral head was translated +/-1.5 mm along the superior-inferior axis
      for 50,000 cycles for characterization of glenoid rocking and inferior-superior
      translation. RESULTS: Glenoid compression and glenoid distraction followed
      similar patterns for PT-backed glenoids. Overall, the all-polyethylene cemented
      glenoid demonstrated superior fixation compared to all PT-backed groups
      throughout the test. Glenoids fixed with PMMA cement displayed more favorable
      initial fixation and resistance to glenoid motion throughout cyclic testing.
      CONCLUSION: This study showed that among PT-backed glenoids, PMMA fixation
      provided an increase in stability during initial and final cycles compared to
      press-fit and calcium-phosphate fixation techniques. This improved stability may
      enhance the osteointegration of the implant.

PMID- 22999849
TI  - Recurrent anterior shoulder dislocation due to a partial-thickness articular
      surface supraspinatus tendon tear without capsulolabral lesion.

PMID- 22999850
TI  - Effects of glenosphere positioning on impingement-free internal and external
      rotation after reverse total shoulder arthroplasty.
AB  - INTRODUCTION: Patients may experience a loss of internal rotation (IR) and
      external rotation (ER) after reverse total shoulder arthroplasty (RTSA). We
      hypothesized that alterations in the glenosphere position will affect the amount
      of impingement-free IR and ER. MATERIALS AND METHODS: Computed tomography (CT)
      scans of the scapula and humerus were obtained from 7 cadaveric specimens, and 3
      dimensional reconstructions were created. RTSA models were virtually implanted
      into each specimen. The glenosphere position was determined in relation to the
      neutral position in 7 settings: medialization (5 mm), lateralization (10 mm),
      superior translation (6 mm), inferior translation (6 mm), superior tilt (20
      degrees ), and inferior tilt (15 degrees  and 30 degrees ). The humerus in each
      virtual model was allowed to freely rotate at a fixed scaption angle (0 degrees ,
      20 degrees , 40 degrees , and 60 degrees ) until encountering bone-to-bone or
      bone-to-implant impingement (180 degrees  of limitation). Measurements were
      recorded for each scaption angulation. RESULTS: At 0 degrees  scaption, only
      inferior translation, lateralization, and inferior tilt (30 degrees ) allowed any
      impingement-free motion in IR and ER. At the midranges of scaption (20 degrees 
      and 40 degrees ), increased lateralization and inferior translation resulted in
      improved rotation. Supraphysiologic motion (>90 degrees  rotation) was seen
      consistently at 60 degrees  of scaption in IR. Superior translation (6 mm)
      resulted in no rotation at 0 degrees  and 20 degrees  of scaption for IR and ER.
      CONCLUSIONS: Glenosphere position significantly affected humeral IR and ER after
      RTSA. Superior translation resulted in significant restrictions on IR and ER.
      Optimal glenosphere positioning was achieved with inferior translation, inferior
      tilt, and lateralization in all degrees of scaption.

PMID- 22999851
TI  - Inflammatory cytokines are overexpressed in the subacromial bursa of frozen
      shoulder.
AB  - BACKGROUND: Frozen shoulder is a debilitating condition characterized by gradual
      loss of glenohumeral motion with chronic inflammation and capsular fibrosis. Yet
      its pathogenesis remains largely unknown. We hypothesized that the subacromial
      bursa may be responsible for the pathogenesis of frozen shoulder by producing
      inflammatory cytokines. MATERIALS AND METHODS: We obtained joint capsules and
      subacromial bursae from 14 patients with idiopathic frozen shoulder and from 7
      control subjects to determine the expression levels of interleukin (IL) 1alpha,
      IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), cyclooxygenase (COX) 1,
      and COX-2 by real-time reverse transcriptase-polymerase chain reaction,
      immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: IL-1alpha,
      IL-1beta, TNF-alpha, COX-1, and COX-2 were expressed at significantly high levels
      in the joint capsules of the frozen shoulder group compared with those of the
      control group. Intriguingly, IL-1alpha, TNF-alpha, and COX-2 were also expressed
      at significantly high levels in the subacromial bursae of the frozen shoulder
      group compared with those of the control group. Immunohistochemical analysis
      showed increased expression of COX-2 in both the joint capsules and subacromial
      bursae of the frozen shoulder group. CONCLUSIONS: These findings imply that
      elevated levels of inflammatory cytokines in the subacromial bursa may be
      associated with the pathogenesis of inflammation evolving into fibrosis.

PMID- 22999852
TI  - The effect of biceps adhesions on glenohumeral range of motion: a cadaveric
      study.
AB  - BACKGROUND: Previous studies have demonstrated that the humerus slides along the
      long head of the biceps tendon (LHBT). Blocking this motion may result in
      decreased glenohumeral (GH) range of motion (ROM). The goal of the study was to
      characterize the excursion of the LHBT and measure the effect of biceps adhesions
      on GH ROM. MATERIALS AND METHODS: A custom biomechanical testing setup was used
      to measure the excursion of the LHBT and rotation of the humerus at 0 degrees ,
      15 degrees , 30 degrees , 60 degrees , and 90 degrees  of GH abduction in the
      scapular plane. An in situ biceps tenodesis with the biceps anchor still intact,
      thus simulating biceps adhesions, was sequentially performed in 2 positions: 0
      degrees  abduction and maximum external rotation, followed by 0 degrees 
      abduction and maximum internal rotation. The effect of tenodesis on ROM was
      measured. RESULTS: There was an average excursion of 19.4 +/- 5.4 mm of the LHBT
      as the humerus was taken through ROM in the scapular plane. Tenodesis in 0
      degrees  abduction and maximum internal rotation resulted in a significant
      decrease in GH external rotation of 47.3 degrees  +/- 12.2 degrees  (P = .007)
      with the arm in 0 degrees  abduction. CONCLUSIONS: Tenodesis in maximum internal
      rotation limited rotation significantly, such that in situ tenodesis without
      proximal tenotomy should not be performed. Furthermore, in situations where the
      biceps is at risk for scarring, such as proximal humeral fractures, shoulder
      arthroplasty, and the stiff shoulder, the biomechanical consequence of biceps
      adhesions may be similar to in situ tenodesis and may limit ROM and clinical
      outcomes.

PMID- 22999853
TI  - Functional roles of YPT31 and YPT32 in clotrimazole resistance of Saccharomyces
      cerevisiae through effects on vacuoles and ATP-binding cassette transporter(s).
AB  - We identified YPT31, which is involved in Golgi traffic, as a clotrimazole (CTZ)
      resistance gene in a multicopy library screen. Multicopies of the YPT31 homolog
      YPT32 also conferred resistance to CTZ, and single disruption of YPT31 or YPT32
      resulted in sensitivity to CTZ. Pdr5p, an ATP-binding cassette (ABC) transporter
      at the plasma membrane, was the most important factor for mediating basal
      resistance to CTZ, suggesting that Ypt31p and Ypt32p might be involved in the
      trafficking of Pdr5p to the plasma membrane. However, the activity of Pdr5p was
      independent of YPT31 or YPT32, and multicopies of YPT31 or YPT32 still conferred
      resistance to CTZ in pdr5 cells. To elucidate the roles of YPT31 and YPT32 in CTZ
      resistance, we analyzed mutants of 11 genes that are involved in the following
      vesicular trafficking: Golgi traffic (kes1, trs33, trs65, gyp1, trs85, and gyp2),
      vacuole inheritance (ypt7), endocytosis (rcy1 and ypt51) and exocytosis (msb3 and
      msb4). All of the mutant cells except ypt51, msb3 and msb4 were sensitive to CTZ,
      indicating that vacuoles were involved in CTZ resistance, since vacuole formation
      requires proper Golgi-trafficking and endocytosis. Microscopic analysis showed
      abnormal vacuoles in ypt31 cells. Multicopies of YPT31 or YPT32 conferred
      resistance to CTZ in AD1-8 cells, which are defective in seven major drug
      transporters, and in pdr5 ypt7 cells, but not in ypt7 or AD1-8-7 (AD1-8/ypt7)
      cells. These results indicated that Ypt31p and Ypt32p played minor but
      compensatory roles in cellular resistance to CTZ through vacuoles and specific
      ABC transporter(s) other than Pdr5p.

PMID- 22999854
TI  - [Factsheets: support in the analysis of recipients' adverse reactions].
AB  - In order to help the analysis of adverse effects of transfusion, factsheets have
      been written by working groups of the French agency for the safety of health
      products ANSM. Each factsheet deals with a blood transfusion side effect and is
      composed of five parts, including pathophysiological mechanisms, diagnostic
      criteria, management recommendations, etiologic investigations and rules for
      filing the notification form to ANSM. Since 2006, 11 factsheets have been
      published on the French haemovigilance network website. The major characteristics
      of the two last sheets published "post-transfusion purpura" and "non erythrocyte
      incompatibility reaction" are presented, followed by the updated card for
      "allergy". These factsheets give relevant guidelines allowing better evaluation
      of recipients' adverse reactions, particularly their diagnosis, severity and
      accountability. They also could initiate studies among European and international
      haemovigilance networks.

PMID- 22999855
TI  - [Therapeutic plasmas].
AB  - Three different therapeutic plasmas preparations are currently available in
      France and are issued by EFS to the hospitals: quarantine fresh frozen plasma,
      amotosalen-inactivated plasma and solvent/detergent-treated plasma. All these
      products insure a microbiological safety, an immunologic compatibility and a
      hemostatic potential for the patients. These plasmas are in accordance with the
      Guidelines established by the French Authorities (ANSM).

PMID- 22999856
TI  - Global health diplomacy: an integrative review of the literature and implications
      for nursing.
AB  - The increasing interconnectedness of the world and the factors that affect health
      lay the foundation for the evolving practice of global health diplomacy. There
      has been limited discussion in the nursing literature about the concept of global
      health diplomacy or the role of nurses in such initiatives. A discussion of this
      concept is presented here by the members of a Task Force on Global Health
      Diplomacy of the American Academy of Nursing Expert Panel on Global Nursing and
      Health (AAN EPGNH). The purpose of this article is to present an integrative
      review of literature on the concept of global health diplomacy and to identify
      implications of this emerging field for nursing education, practice, and
      research. The steps proposed by Whittemore and Knafl (2005) were adapted and
      applied to the integrative review of theoretical and descriptive articles about
      the concept of global health diplomacy. This review included an analysis of the
      historical background, definition, and challenges of global health diplomacy and
      suggestions about the preparation of global health diplomats. The article
      concludes with a discussion of implications for nursing practice, education, and
      research. The Task Force endorses the definition of global health diplomacy
      proposed by Adams, Novotny, and Leslie (2008) but recommends that further
      dialogue and research is necessary to identify opportunities and educational
      requirements for nurses to contribute to the emerging field of global health
      diplomacy.

PMID- 22999857
TI  - Chromatin immunoprecipitation and microarray analysis reveal that TFIIB occupies
      the SL RNA gene promoter region in Trypanosoma brucei chromosomes.
AB  - RNA polymerase II (RNAP-II) synthesizes the m(7)G-capped Spliced Leader (SL) RNA
      and most protein-coding mRNAs in trypanosomes. RNAP-II recruitment to DNA usually
      requires a set of transcription factors that make sequence-specific contacts near
      transcriptional start sites within chromosomes. In trypanosomes, the
      transcription factor TFIIB is necessary for RNAP-II-dependent SL RNA
      transcription. However, the trypanosomal TFIIB (tTFIIB) lacks the highly basic
      DNA binding region normally found in the C-terminal region of TFIIB proteins. To
      assess the precise pattern of tTFIIB binding within the SL RNA gene locus, as
      well as within several other loci, we performed chromatin
      immunoprecipitation/microarray analysis using a tiled gene array with a probe
      spacing of 10 nucleotides. We found that tTFIIB binds non-randomly within the SL
      RNA gene locus mainly within a 220-nt long region that straddles the
      transcription start site. tTFIIB does not bind within the small subunit (SSU)
      rRNA locus, indicating that trypanosomal TFIIB is not a component of an RNAP-I
      transcriptional complex. Interestingly, discrete binding sites were observed
      within the putative promoter regions of two loci on different chromosomes. These
      data suggest that although trypanosomal TFIIB lacks a highly basic DNA binding
      region, it nevertheless localizes to discrete regions of chromatin that include
      the SL RNA gene promoter.

PMID- 22999858
TI  - A consensus-based approach to patient safety in epilepsy monitoring units:
      recommendations for preferred practices.
AB  - Patients in an epilepsy monitoring unit (EMU) with video-EEG telemetry have a
      risk for seizure emergencies, injuries and adverse events, which emphasizes the
      need for strategies to prevent avoidable harm. An expert consensus process was
      used to establish recommendations for patient safety in EMUs. Workgroups analyzed
      literature and expert opinion regarding seizure observation, seizure provocation,
      acute seizures, and activity/environment. A Delphi methodology was used to
      establish consensus for items submitted by these workgroups. Fifty-three items
      reached consensus and were organized into 30 recommendations. High levels of
      agreement were noted for items pertaining to orientation, training,
      communication, seizure precautions, individualized plans, and patient/family
      education. It was agreed that seizure observation should include direct
      observation or use of closed-circuit camera. The use of continuous observation
      was strongest in patients with invasive electrodes, at high risk for injury, or
      undergoing AED withdrawal. This process provides a first step in establishing EMU
      safety practices.

PMID- 22999859
TI  - Outer membrane vesicles of a human commensal mediate immune regulation and
      disease protection.
AB  - Commensal bacteria impact host health and immunity through various mechanisms,
      including the production of immunomodulatory molecules. Bacteroides fragilis
      produces a capsular polysaccharide (PSA), which induces regulatory T cells and
      mucosal tolerance. However, unlike pathogens, which employ secretion systems, the
      mechanisms by which commensal bacteria deliver molecules to the host remain
      unknown. We reveal that Bacteroides fragilis releases PSA in outer membrane
      vesicles (OMVs) that induce immunomodulatory effects and prevent experimental
      colitis. Dendritic cells (DCs) sense OMV-associated PSA through TLR2, resulting
      in enhanced regulatory T cells and anti-inflammatory cytokine production. OMV
      induced signaling in DCs requires growth arrest and DNA-damage-inducible protein
      (Gadd45alpha). DCs treated with PSA-containing OMVs prevent experimental colitis,
      whereas Gadd45alpha(-/-) DCs are unable to promote regulatory T cell responses or
      suppress proinflammatory cytokine production and host pathology. These findings
      demonstrate that OMV-mediated delivery of a commensal molecule prevents disease,
      uncovering a mechanism of interkingdom communication between the microbiota and
      mammals.

PMID- 22999860
TI  - Rapamycin protects against myocardial ischemia-reperfusion injury through JAK2
      STAT3 signaling pathway.
AB  - Rapamycin (Sirolimus(r)) is used to prevent rejection of transplanted organs and
      coronary restenosis. We reported that rapamycin induced cardioprotection against
      ischemia-reperfusion (I/R) injury through opening of mitochondrial K(ATP)
      channels. However, signaling mechanisms in rapamycin-induced cardioprotection are
      currently unknown. Considering that STAT3 is protective in the heart, we
      investigated the potential role of this transcription factor in rapamycin-induced
      protection against (I/R) injury. Adult male ICR mice were treated with rapamycin
      (0.25mg/kg, i.p.) or vehicle (DMSO) with/without inhibitor of JAK2 (AG-490) or
      STAT3 (stattic). One hour later, the hearts were subjected to I/R either in
      Langendorff mode or in situ ligation of left coronary artery. Additionally,
      primary murine cardiomyocytes were subjected to simulated ischemia-reoxygenation
      (SI/RO) injury in vitro. For in situ targeted knockdown of STAT3, lentiviral
      vector containing short hairpin RNA was injected into the left ventricle 3 weeks
      prior to initiating I/R injury. Infarct size, cardiac function, and cardiomyocyte
      necrosis and apoptosis were assessed. Rapamycin reduced infarct size, improved
      cardiac function following I/R, and limited cardiomyocyte necrosis as well as
      apoptosis following SI/RO which were blocked by AG-490 and stattic. In situ knock
      down of STAT3 attenuated rapamycin-induced protection against I/R injury.
      Rapamycin triggered unique cardioprotective signaling including phosphorylation
      of ERK, STAT3, eNOS and glycogen synthase kinase-3beta in concert with increased
      prosurvival Bcl-2 to Bax ratio. Our data suggest that JAK2-STAT3 signaling plays
      an essential role in rapamycin-induced cardioprotection. We propose that
      rapamycin is a novel and clinically relevant pharmacological strategy to target
      STAT3 activation for treatment of myocardial infarction.

PMID- 22999861
TI  - Endothelial differentiation in multipotent cells derived from mouse and human
      white mature adipocytes.
AB  - White mature adipocytes give rise to multipotent cells, so-called de
      differentiated fat (DFAT) cells, when losing their fat in culture. The objective
      of this study was to examine the ability of DFAT cells to give rise to
      endothelial cells (ECs) in vitro and vivo. We demonstrate that mouse and human
      DFAT cells, derived from adipose tissue and lipospirate, respectively, initially
      lack expression of CD34, CD31, CD146, CD45 and pericyte markers, distinguishing
      them from progenitor cells previously identified in adipose stroma. The DFAT
      cells spontaneously differentiate into vascular ECs in vitro, as determined by
      real-time PCR, fluorescence activated cell sorting, immunostaining, and formation
      of tube structures. Treatment with bone morphogenetic protein (BMP)4 and BMP9,
      important in regulating angiogenesis, significantly enhances the EC
      differentiation. Furthermore, adipocyte-derived cells from Green Fluorescent
      Protein-transgenic mice were detected in the vasculature of infarcted myocardium
      up to 6 weeks after ligation of the left anterior descending artery in mice. We
      conclude that adipocyte-derived multipotent cells are able to spontaneously give
      rise to ECs, a process that is promoted by BMPs and may be important in
      cardiovascular regeneration and in physiological and pathological changes in fat
      and other tissues.

PMID- 22999862
TI  - Characteristics of pericardial interstitial cells and their implications in
      pericardial fibrocalcification.
AB  - Pericardial fibrocalcification (PF) is a prominent feature of human pericardial
      pathology, including constrictive pericarditis and, to a lesser extent,
      degenerated autologous pericardial substitutes. However, the role of pericardial
      interstitial cells (PICs) in the pathogenesis of PF has yet to be established.
      Using a combination of histology and immunohistochemistry, we showed that the
      critical cellular event in PF in situ was the transdifferentiation of PICs into
      myofibroblasts/osteoblasts and that the percentage of myofibroblasts/osteoblasts
      correlated positively with the severity of PF. In vitro studies demonstrated that
      PICs, similar to mesenchymal stem cells, had the potential to differentiate along
      adipogenic, osteogenic, chondrogenic or myogenic lineages. However, PICs
      exhibited a more limited self-renewal capacity and a lower expression of Oct4
      (POU5F1) and Kruppel-like transcription factor Klf4, underwent earlier senescence
      and spontaneously transdifferentiated into myofibroblasts/osteoblasts.
      Quantitative-real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)
      confirmed that the mRNA levels of alpha-smooth muscle actin (alpha-SMA), alkaline
      phosphatase (ALP), core-binding factor alpha1/runt-related transcription factor2
      (Cbfa1/Runx2), transforming growth factor (TGF)-beta1 and bone morphogenetic
      protein (BMP)-2 were upregulated as the passage number increased. The mRNA level
      of platelet-derived growth factor (PDGF)-AA was also significantly upregulated
      with higher levels at passage 3. Ectopic expression of Oct4 and Klf4 enhanced the
      colony formation of PICs and selectively impaired induction of genes involved in
      transdifferentiation into myofibroblasts/osteoblasts (alpha-SMA, ALP,
      Cbfa1/Runx2, PDGF-AA and BMP-2). These data, while offering new insights into the
      biology of PICs, reinforce the central role of these cells in cell-mediated PF
      and may assist in future strategies to treat fibrocalcific pericardial diseases.

PMID- 22999863
TI  - Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T
      cell mediating anti-tumor immune response.
AB  - Macrophages are the prominent components of solid tumors and have complex dual
      functions in their interaction with cancer cells. Strong evidence suggests that
      TAM is a part of inflammatory circuits that promote tumor progression. B7
      homologue 3 (B7-H3), a recently identified homologue of B7.1/2 (CD80/86), has
      been described to exert co-stimulatory and immune regulatory functions. Here, we
      showed that a fraction of macrophages in tumor stroma expressed surface B7-H3
      molecule. Normal macrophages, which did not express B7-H3, would be induced
      expressing B7-H3 molecule when culturing with tumor cell. Although a lung cancer
      cell line constitutively expressed B7-H3 mRNA and protein in plasma, primary
      tumor cell isolated from the transplanted lung carcinoma model expressed B7-H3 on
      the surface. Interestingly, in transplanted lung carcinoma model, the expression
      of membrane-bound B7-H3 in tumor cells was increased as prolonging of tumor
      transformation. In support, IL-10 released from TAM could stimulate cancer cell
      expression of membrane bound B7-H3. Furthermore, Lung cancer and TAM-related B7
      H3 was identified as a strong inhibitor of T-cell effect and influenced the
      outcome of T cell immune response. In conclusion, TAM-tumor cell interaction
      induced membrane-bound B7-H3 represents a novel immune escape mechanism which
      links the pro-inflammatory response to immune tolerance in the tumor milieu.

PMID- 22999865
TI  - Autophagic lysosome reformation.
AB  - Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway.
      In recent years, many important advances have been made in understanding the
      cellular and molecular mechanism of autophagosome formation. However, the late
      stages of autophagy-the cellular events after formation of the autolysosome-are
      relatively rarely studied. In this review, we discussed the cellular process and
      molecular mechanism of autophagic lysosome reformation, a cellular events which
      defines the terminal stage of autophagy.

PMID- 22999864
TI  - Biology and clinical implications of CD133(+) liver cancer stem cells.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the
      liver, accounting for 80%-90% of all liver cancers. The disease ranks as the
      fifth most common cancer worldwide and is the third leading cause of all cancer
      associated deaths. Although advances in HCC detection and treatment have
      increased the likelihood of a cure at early stages of the disease, HCC remains
      largely incurable because of late presentation and tumor recurrence. Only 25% of
      HCC patients are deemed suitable for curative treatment, with the overall
      survival at just a few months for inoperable patients. Apart from surgical
      resection, loco-regional ablation and liver transplantation, current treatment
      protocols include conventional cytotoxic chemotherapy. But due to the highly
      resistant nature of the disease, the efficacy of the latter regimen is limited.
      The recent emergence of the cancer stem cell (CSC) concept lends insight into the
      explanation of why treatment with chemotherapy often may seem to be initially
      successful but results in not only a failure to eradicate the tumor but also
      possibly tumor relapse. Commonly used anti-cancer drugs in HCC work by targeting
      the rapidly proliferating and differentiated liver cancer cells that constitute
      the bulk of the tumor. However, a subset of CSCs exists within the tumor, which
      are more resistant and are able to survive and maintain residence after
      treatment, thus, growing and self-renewing to generate the development and spread
      of recurrent tumors in HCC. In the past few years, compelling evidence has
      emerged in support of the hierarchic CSC model for solid tumors, including HCC.
      And in particular, CD133 has drawn significant attention as a critical liver CSC
      marker. Understanding the characteristics and function of CD133(+) liver CSCs has
      also shed light on HCC management and treatment, including the implications for
      prognosis, prediction and treatment resistance. In this review, a detailed
      summary of the recent progress in CD133(+) liver CSC research with regard to
      identification, regulation and clinical implications will be discussed.

PMID- 22999867
TI  - GSK3 inhibition prevents lethal GVHD in mice.
AB  - Graft-versus-host disease (GVHD) is a major contributor to transplant-related
      mortality and morbidity after allogeneic stem cell transplantation. Despite
      advancements in tissue-typing techniques, conditioning regimens, and therapeutic
      intervention, the incidence rate of GVHD remains high. GVHD is caused by
      alloreactive donor T cells that infiltrate and destroy host tissues (e.g., skin,
      liver, and gut). Therefore, GVHD is prevented and treated with therapeutics that
      suppress proinflammatory cytokines and T-cell function (e.g., cyclosporine,
      glucocorticoids). Here we report that the small molecule inhibitor of glycogen
      synthase kinase 3, 6-bromoindirubin 3'-oxime (BIO), prevents lethal GVHD in a
      humanized xenograft model in mice. BIO treatment did not affect donor T-cell
      engraftment, but suppressed their activation and attenuated bone marrow and liver
      destruction mediated by activated donor T cells. Glycogen synthase kinase 3
      inhibition modulated the Th1/Th2 cytokine profile in vitro and suppressed
      activation of signal transducers and activators of transcription 1 and 3
      signaling pathways both in vitro and in vivo. Importantly, human T cells derived
      from BIO-treated mice were able to mediate anti-tumor effects in vitro, and BIO
      did not affect stem cell engraftment and multilineage reconstitution in a mouse
      model of transplantation. These data demonstrate that inhibition of glycogen
      synthase kinase 3 can potentially abrogate GVHD without compromising the efficacy
      of transplantation.

PMID- 22999868
TI  - Focus issue--Analysis and biostatistical interpretation of complex and low
      template DNA samples.

PMID- 22999869
TI  - Genetic variation at 15 autosomal STR loci in the Hungarian population of
      Vojvodina Province, Republic of Serbia.

PMID- 22999866
TI  - Skeletal muscle neural progenitor cells exhibit properties of NG2-glia.
AB  - Reversing brain degeneration and trauma lesions will depend on cell therapy. Our
      previous work identified neural precursor cells derived from the skeletal muscle
      of Nestin-GFP transgenic mice, but their identity, origin, and potential survival
      in the brain are only vaguely understood. In this work, we show that Nestin-GFP+
      progenitor cells share morphological and molecular markers with NG2-glia,
      including NG2, PDGFRalpha, O4, NGF receptor (p75), glutamate receptor-1(AMPA),
      and A2B5 expression. Although these cells exhibit NG2, they do not express other
      pericyte markers, such as alpha-SMA or connexin-43, and do not differentiate into
      the muscle lineage. Patch-clamp studies displayed outward potassium currents,
      probably carried through Kir6.1 channels. Given their potential therapeutic
      application, we compared their abundance in tissues and concluded that skeletal
      muscle is the richest source of predifferentiated neural precursor cells. We
      found that these cells migrate toward the neurogenic subventricular zone
      displaying their typical morphology and nestin-GFP expression two weeks after
      brain injection. For translational purposes, we sought to identify these neural
      progenitor cells in wild-type species by developing a DsRed expression vector
      under Nestin-Intron II control. This approach revealed them in nonhuman primates
      and aging rodents throughout the lifespan.

PMID- 22999870
TI  - The impact of under and over-recording of cancer on death certificates in a
      competing risks analysis: a simulation study.
AB  - BACKGROUND: With linked register and cause of death data becoming more accessible
      than ever, competing risks methodology is being increasingly used as a way of
      obtaining "real world" probabilities of death broken down by specific causes. It
      is important, in terms of the validity of these studies, to have accurate cause
      of death information. However, it is well documented that cause of death
      information taken from death certificates is often lacking in accuracy and
      completeness. METHODS: We assess through use of a simulation study the effect of
      under and over-recording of cancer on death certificates in a competing risks
      analysis consisting of three competing causes of death: cancer, heart disease and
      other causes. Using realistic levels of misclassification, we consider 24
      scenarios and examine the bias in the cause-specific hazard ratios and the
      cumulative incidence function. RESULTS: The bias in the cumulative incidence
      function was highest in the oldest age group reaching values as high as 2.6
      percentage units for the "good" cancer prognosis scenario and 9.7 percentage
      units for the "poor" prognosis scenario. CONCLUSION: The bias resulting from the
      chosen levels of misclassification in this study accentuate concerns that
      unreliable cause of death information may be providing misleading results. The
      results of this simulation study convey an important message to applied
      epidemiological researchers.

PMID- 22999871
TI  - Ariad Pharmaceutical's ninja cancer drug inhibits armies of mutants.

PMID- 22999872
TI  - "Prohibitin"g CRAF/MAPK activation with rocaglamides.
AB  - Interaction with prohibitin (PHB) is required for full activation of CRAF kinase,
      the central member of the highly conserved RAS-CRAF-MAPK pathway. In this issue
      of Chemistry & Biology, Polier et al. show that the natural anti-tumor compounds
      rocaglamides target the CRAF-PHB interaction to disrupt the MAPK pathway leading
      to proliferation block in human leukemic cells.

PMID- 22999873
TI  - Interaction of the glucocorticoid and androgen receptors in adipogenesis.
AB  - Glucocorticoids and androgens are important regulators of adipose tissue
      function. A new study by Hartig et al. in this issue of Chemistry & Biology
      provides relevant information regarding androgen receptor activity and its link
      to glucocorticoid action in human adipocytes during the process of preadipocyte
      differentiation.

PMID- 22999874
TI  - Fine-tuning S1P therapeutics.
AB  - Sphingosine 1-phosphate receptor-1 (S1P(1)), a novel therapeutic target for
      multiple sclerosis, regulates lymphocyte trafficking, heart rate, and vascular
      function. The discovery of NIBR-0213, a competitive antagonist for S1P(1) that
      inhibits autoimmune inflammation while sparing bradycardia (Quancard et al., in
      this issue of Chemistry & Biology), suggests that fine-tuning of S1P(1)
      modulators may lead to novel immune modulators with better efficacy to adverse
      events ratio.

PMID- 22999875
TI  - The secret of MIM: a novel, MCL-1-specific small molecule.
AB  - Reactivating apoptosis is a major goal of cancer research, and MCL-1 has emerged
      as a primary pharmacological target. A screen for small molecules that could
      compete with stabilized helical peptides for MCL-1 binding yielded small molecule
      MIM1 (see the article by Cohen et al. in this issue of Chemistry & Biology). MIM1
      selectively targets MCL-1, and can kill MCL-1-dependent leukemia cells.

PMID- 22999876
TI  - Small-molecule reprogramming of cancer metabolism.
AB  - Small molecules that inhibit common cancer-associated changes in metabolism have
      great potential as widely applicable therapies. In this issue of Chemistry &
      Biology, Kung et al. report the characterization of a small molecule activator of
      the enzyme pyruvate kinase M2, which reprograms cancer cell metabolism resulting
      in dependence on the amino acid serine.

PMID- 22999877
TI  - Chemistry and biology of biomolecule nitration.
AB  - Posttranslational modifications of proteins play key roles in the regulation of
      biological processes and lead to various physiological responses. In recent
      years, a number of analytical technologies have been developed to help understand
      the diversity and disease relevance of these modifications. The main areas of
      focus have included phosphorylation, cysteine redox chemistry, and
      transformations mediated directly by oxidative stress. However, the nitration of
      biomolecules is an exciting and relatively understudied area of research.
      Reactive nitrogen species generated in various disease states can create nitrated
      biomolecules, and we are only beginning to understand the potential implications
      of these species. This review explores some of the recent advances in current
      knowledge concerning the chemistry and biology of nitrated biomolecules.

PMID- 22999878
TI  - The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by
      targeting prohibitin 1 and 2.
AB  - Rocaglamides are potent natural anticancer products that inhibit proliferation of
      various cancer cells at nanomolar concentrations. We have recently shown that
      these compounds prevent tumor growth and sensitize resistant cancer cells to
      apoptosis by blocking the MEK-ERK-eIF4 pathway. However, their direct molecular
      target(s) remain(s) unknown. In this study, using an affinity chromatography
      approach we discovered that prohibitin (PHB) 1 and 2 are the direct targets of
      rocaglamides. Binding of rocaglamides to PHB prevents interaction between PHB and
      CRaf and, thereby, inhibits CRaf activation and subsequently CRaf-MEK-ERK
      signaling. Moreover, knockdown of PHB mimicked the effects of rocaglamides on the
      CRaf-MEK-ERK pathway and cell cycle progression. Thus, our finding suggests that
      rocaglamides are a new type of anticancer agent and that they may serve as a
      small-molecular tool for studying PHB-mediated cellular processes.

PMID- 22999879
TI  - Fragment screening at adenosine-A(3) receptors in living cells using a
      fluorescence-based binding assay.
AB  - G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane
      proteins. For GPCR drug discovery, it is important that ligand affinity is
      determined in the correct cellular environment and preferably using an unmodified
      receptor. We developed a live cell high-content screening assay that uses a
      fluorescent antagonist, CA200645, to determine binding affinity constants of
      competing ligands at human adenosine-A(1) and -A(3) receptors. This method was
      validated as a tool to screen a library of low molecular weight fragments, and
      identified a hit with submicromolar binding affinity (K(D)). This fragment was
      structurally unrelated to substructures of known adenosine receptor antagonists
      and was optimized to show selectivity for the adenosine-A(3) receptor. This
      technology represents a significant advance that will allow the determination of
      ligand and fragment affinities at receptors in their native membrane environment.

PMID- 22999880
TI  - Insights into a divergent phenazine biosynthetic pathway governed by a plasmid
      born esmeraldin gene cluster.
AB  - Phenazine-type metabolites arise from either phenazine-1-carboxylic acid (PCA) or
      phenazine-1,6-dicarboxylic acid (PDC). Although the biosynthesis of PCA has been
      studied extensively, PDC assembly remains unclear. Esmeraldins and saphenamycin,
      the PDC originated products, are antimicrobial and antitumor metabolites isolated
      from Streptomyces antibioticus Tu 2706. Herein, the esmeraldin biosynthetic gene
      cluster was identified on a dispensable giant plasmid. Twenty-four putative esm
      genes were characterized by bioinformatics, mutagenesis, genetic complementation,
      and functional protein expressions. Unlike enzymes involved in PCA biosynthesis,
      EsmA1 and EsmA2 together decisively promoted the PDC yield. The resulting PDC
      underwent a series of conversions to give 6-acetylphenazine-1-carboxylic acid,
      saphenic acid, and saphenamycin through a unique one-carbon extension by EsmB1
      B5, a keto reduction by EsmC, and an esterification by EsmD1-D3, the atypical
      polyketide sythases, respectively. Two transcriptional regulators, EsmT1 and
      EsmT2, are required for esmeraldin production.

PMID- 22999882
TI  - A potent and selective S1P(1) antagonist with efficacy in experimental autoimmune
      encephalomyelitis.
AB  - Lymphocyte trafficking is critically regulated by the Sphingosine 1-phosphate
      receptor-1 (S1P(1)), a G protein-coupled receptor that has been highlighted as a
      promising therapeutic target in autoimmunity. Fingolimod (FTY720, Gilenya) is a
      S1P(1) receptor agonist that has recently been approved for the treatment of
      multiple sclerosis (MS). Here, we report the discovery of NIBR-0213, a potent and
      selective S1P(1) antagonist that induces long-lasting reduction of peripheral
      blood lymphocyte counts after oral dosing. NIBR-0213 showed comparable
      therapeutic efficacy to fingolimod in experimental autoimmune encephalomyelitis
      (EAE), a model of human MS. These data provide convincing evidence that S1P(1)
      antagonists are effective in EAE. In addition, the profile of NIBR-0213 makes it
      an attractive candidate to further study the consequences of S1P(1) receptor
      antagonism and to differentiate the effects from those of S1P(1) agonists.

PMID- 22999883
TI  - Substrate-selective inhibition of protein kinase PDK1 by small compounds that
      bind to the PIF-pocket allosteric docking site.
AB  - The PIF-pocket of AGC protein kinases participates in the physiologic mechanism
      of regulation by acting as a docking site for substrates and as a switch for the
      transduction of the conformational changes needed for activation or inhibition.
      We describe the effects of compounds that bind to the PIF-pocket of PDK1. In
      vitro, PS210 is a potent activator of PDK1, and the crystal structure of the PDK1
      ATP-PS210 complex shows that PS210 stimulates the closure of the kinase domain.
      However, in cells, the prodrug of PS210 (PS423) acts as a substrate-selective
      inhibitor of PDK1, inhibiting the phosphorylation and activation of S6K, which
      requires docking to the PIF-pocket, but not affecting PKB/Akt. This work
      describes a tool to study the dynamics of PDK1 activity and a potential approach
      for drug discovery.

PMID- 22999881
TI  - Feed-forward inhibition of androgen receptor activity by glucocorticoid action in
      human adipocytes.
AB  - We compared transcriptomes of terminally differentiated mouse 3T3-L1 and human
      adipocytes to identify cell-specific differences. Gene expression and high
      content analysis (HCA) data identified the androgen receptor (AR) as both
      expressed and functional, exclusively during early human adipocyte
      differentiation. The AR agonist dihydrotestosterone (DHT) inhibited human
      adipocyte maturation by downregulation of adipocyte marker genes, but not in 3T3
      L1. It is interesting that AR induction corresponded with dexamethasone
      activation of the glucocorticoid receptor (GR); however, when exposed to the
      differentiation cocktail required for adipocyte maturation, AR adopted an
      antagonist conformation and was transcriptionally repressed. To further explore
      effectors within the cocktail, we applied an image-based support vector machine
      (SVM) classification scheme to show that adipocyte differentiation components
      inhibit AR action. The results demonstrate human adipocyte differentiation, via
      GR activation, upregulates AR but also inhibits AR transcriptional activity.

PMID- 22999884
TI  - Biosynthesis of the respiratory toxin bongkrekic acid in the pathogenic bacterium
      Burkholderia gladioli.
AB  - Bongkrekic acid (BA), an infamous respiratory toxin of the pathogenic bacterium
      Burkholderia gladioli, causes lethal intoxications when tempe bongkrek is
      produced with contaminated Rhizopus oligosporus cultures. Genome sequencing of B.
      gladioli pathovar cocovenenans unveiled the genetic basis for BA biosynthesis,
      and pointed to a homologous bon gene cluster in a B. gladioli strain from an
      infected rice plant. For functional genetics in B. gladioli lambda Red
      recombination was established. Dissection of the modular type I polyketide
      synthase (a trans-AT PKS) provided insights into complex polyketide assembly.
      Isoprenoid-like beta-branching events and a six-electron oxidation of a methyl
      group to a carboxylic acid give rise to the unique branched tricarboxylic fatty
      acid. The role of the cytochrome P450 monooxygenase, BonL, was proven by
      structural elucidation of deoxybongkrekic acid from a mutant.

PMID- 22999885
TI  - A competitive stapled peptide screen identifies a selective small molecule that
      overcomes MCL-1-dependent leukemia cell survival.
AB  - Cancer cells hijack BCL-2 family survival proteins to suppress the death
      effectors and thereby enforce an immortal state. This is accomplished
      biochemically by an antiapoptotic surface groove that neutralizes the
      proapoptotic BH3 alpha helix of death proteins. Antiapoptotic MCL-1 in particular
      has emerged as a ubiquitous resistance factor in cancer. Although targeting the
      BCL-2 antiapoptotic subclass effectively restores the death pathway in BCL-2
      dependent cancer, the development of molecules tailored to the binding
      specificity of MCL-1 has lagged. We previously discovered that a hydrocarbon
      stapled MCL-1 BH3 helix is an exquisitely selective MCL-1 antagonist. By
      deploying this unique reagent in a competitive screen, we identified an MCL-1
      inhibitor molecule that selectively targets the BH3-binding groove of MCL-1,
      neutralizes its biochemical lock-hold on apoptosis, and induces caspase
      activation and leukemia cell death in the specific context of MCL-1 dependence.

PMID- 22999887
TI  - In vivo imaging of inflammatory phagocytes.
AB  - Inflammation contributes to the pathophysiology of many diseases. In this report,
      we present noninvasive bioluminescence imaging methods that distinguish acute and
      chronic inflammation in mouse models. Systemic delivery of luminol (5-amino-2,3
      dihydro-1,4-phthalazinedione) enables detection of acute inflammation largely
      mediated by tissue-infiltrating neutrophils, whose myeloperoxidase (MPO) activity
      is required for luminol bioluminescence. In contrast, bioluminescence from
      injection of lucigenin (bis-N-methylacridinium nitrate) closely correlates with
      late phase and chronic inflammation. Lucigenin bioluminescence is independent of
      MPO and, instead, requires phagocyte NADPH oxidase (Phox) activity in
      macrophages. We are able to visualize tissue inflammation resulting from wound
      healing, bacterial infection, foreign substance implantation, and antitumor
      immune responses. Given the central role of inflammation in a variety of
      disorders, we believe these noninvasive imaging methods can help dissect the
      differential roles of neutrophils and macrophages in a variety of pathological
      conditions.

PMID- 22999886
TI  - Small molecule activation of PKM2 in cancer cells induces serine auxotrophy.
AB  - Proliferating tumor cells use aerobic glycolysis to support their high metabolic
      demands. Paradoxically, increased glycolysis is often accompanied by expression
      of the lower activity PKM2 isoform, effectively constraining lower glycolysis.
      Here, we report the discovery of PKM2 activators with a unique allosteric binding
      mode. Characterization of how these compounds impact cancer cells revealed an
      unanticipated link between glucose and amino acid metabolism. PKM2 activation
      resulted in a metabolic rewiring of cancer cells manifested by a profound
      dependency on the nonessential amino acid serine for continued cell
      proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied
      by reduced carbon flow into the serine biosynthetic pathway and increased
      expression of high affinity serine transporters. These data support the
      hypothesis that PKM2 expression confers metabolic flexibility to cancer cells
      that allows adaptation to nutrient stress.

PMID- 22999889
TI  - Probing the diverse landscape of protein flexibility and binding.
AB  - Protein flexibility spans a broad spectrum, from highly stable folded to
      intrinsically disordered states. In this review, we discuss how various
      techniques, including X-ray crystallography, nuclear magnetic resonance
      spectroscopy and ensemble-modeling strategies employing various experimental
      measurements, have enabled detailed structural and dynamic characterizations of
      proteins in their free and bound states. This has revealed a variety of possible
      binding scenarios in which flexibility can either decrease or increase upon
      binding. Furthermore, dynamic free-state ensembles have repeatedly been observed
      to contain transiently formed conformations that partially or completely resemble
      bound states. These results demonstrate an intimate connection between protein
      flexibility and protein interactions and illustrate the huge diversity of
      structure and dynamics in both free proteins and protein complexes.

PMID- 22999888
TI  - Crystal structures of 70S ribosomes bound to release factors RF1, RF2 and RF3.
AB  - Termination is a crucial step in translation, most notably because premature
      termination can lead to toxic truncated polypeptides. Most interesting is the
      fact that stop codons are read by a completely different mechanism from that of
      sense codons. In recent years, rapid progress has been made in the structural
      biology of complexes of bacterial ribosomes bound to translation termination
      factors, much of which has been discussed in earlier reviews [1-5]. Here, we
      present a brief overview of the structures of bacterial translation termination
      complexes. The first part summarizes what has been learned from crystal
      structures of complexes containing the class I release factors RF1 and RF2. In
      the second part, we discuss the results and implications of two recent X-ray
      structures of complexes of ribosomes bound to the translational GTPase RF3. These
      structures have provided many insights and a number of surprises. While
      structures alone do not tell us how these complicated molecular assemblies work,
      is it nevertheless clear that it will not be possible to understand their
      mechanisms without detailed structural information.

PMID- 22999890
TI  - Retrospective monitoring of perfluorocarboxylates and perfluorosulfonates in
      human plasma archived by the German Environmental Specimen Bank.
AB  - Due to the increased awareness of the ubiquitous contamination of all
      environmental compartments and of human beings with perfluoroalkyl substances
      (PFAS), voluntary withdrawals and shifts in products and manufacturing
      technologies, as well as in regulatory measures, have been made. To investigate
      whether these activities are reflected in the human exposure to PFASS, we
      examined human blood archived by the German Environmental Specimen Bank. Plasma
      samples (n=258, age range 20-29 years) covering the observation period 1982-2010
      were analyzed for eleven perfluoroalkylcarboxylates (C4-C14) and five
      perfluoroalkylsulfonates (C4-C10) by HPLC-MS-MS. We detected
      perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and
      perfluorohexanesulfonate (PFHxS) most often of all PFASs. Following a sharp
      increase from 1982 to 1986, median PFOS concentrations remained in the range of
      20-24ng/mL until the end of the 1990s. Between 2001 and 2010, PFOS concentrations
      decreased steadily to 4ng/mL in plasma. Except for a similar strong increase from
      1982 to 1986, we observed PFOA concentrations fluctuating between 4.8 and
      6.3ng/mL in the following years. Since 2008, ESB data suggest a decreasing trend
      of PFOA. PFHxS concentrations increased continuously between 1982 and 2001 from
      about 1-2ng/mL. After nearly unchanged concentrations until 2005, a downward
      trend of PFHxS in plasma became apparent and in 2010 resulted in levels which
      were about 20% lower than those observed in the early 1980s. In the case of
      shorter and longer chained PFASs, quantification frequencies were between 0 and
      60% and we found no indication of any temporal trends in human plasma
      concentrations. 

PMID- 22999891
TI  - Comorbidity of personality disorders in anxiety disorders: a meta-analysis of 30
      years of research.
AB  - BACKGROUND: A comprehensive meta-analysis to identify the proportions of comorbid
      personality disorders (PD) across the major subtypes of anxiety disorders (AD)
      has not previously been published. METHODS: A literature search identified 125
      empirical papers from the period 1980-2010 on patients with panic disorders,
      social phobia, generalised anxiety, obsessive-compulsive (OCD) and post-traumatic
      stress disorder (PTSD). Several moderators were coded. RESULTS: The rate of any
      comorbid PD was high across all ADs, ranging from .35 for PTSD to .52 for OCD.
      Cluster C PDs occurred more than twice as often as cluster A or B PDs. Within
      cluster C the avoidant PD occurred most frequently, followed by the obsessive
      compulsive and the dependent PD. PTSD showed the most heterogeneous clinical
      picture and social phobia was highly comorbid with avoidant PD. A range of
      moderators were examined, but most were non-significant or of small effects,
      except an early age of onset, which in social phobia increased the risk of an
      avoidant PD considerably. Gender or duration of an AD was not related to
      variation in PD comorbidity. LIMITATIONS: Blind rating of diagnoses was recorded
      from the papers as an indication of diagnostic validity. However, as too few
      studies reported it the validity of the comorbid estimates of PD was less strong.
      CONCLUSIONS: The findings provided support to several of the proposed changes in
      the forthcoming DSM-5. Further comorbidity studies are needed in view of the
      substantial changes in how PDs will be diagnosed in the DSM-5.

PMID- 22999892
TI  - Body mass index and suicidal behaviors: a critical review of epidemiological
      evidence.
AB  - INTRODUCTION: Obesity has been associated with an elevated risk of depression and
      other mental health symptoms. An increasing number of robust prospective studies,
      however, counter-intuitively and consistently suggested that body mass index
      (BMI) was inversely associated with the risk of completed suicide in a dose
      response fashion. The current contribution appraised the epidemiological evidence
      and examined the nature of the purported relationship. METHOD: We conducted a
      systematic review of English publications of original studies using the terms
      "obesity", "overweight", "body mass index", "BMI", "attempted suicide",
      "completed suicide", "suicide ideation", "suicidal behaviors" and "suicide". Data
      were extracted primarily through MEDLINE and PUBMED databases. RESULTS: Almost
      all cohort studies reported an inverse relationship between BMI and the risk of
      completed suicide irrespective of region of origin and the gender of study
      participants. Overall, among men, a high BMI was associated with a low risk of
      attempted or completed suicide. There was a paradox among women, namely, a high
      BMI was associated with an elevated risk of attempted suicide but a low risk of
      completed suicide. LIMITATIONS: As a narrative review, the current report was
      interpretive and qualitative in nature. CONCLUSION: Consideration of
      observational data, methodological issues stemmed from the rarity of deaths by
      suicide, homogeneity of study populations, heterogeneity of suicide methods, and
      the corresponding neurobiological changes made interpretation difficult.
      Intercultural cohort observations across countries may help to weigh the
      contributions from biological and socio-cultural factors. The purported
      association not only represents a scientific challenge, it's also an opportunity
      potentially leading to important insights into prevention of suicide death.

PMID- 22999894
TI  - Obesity and fractures.

PMID- 22999893
TI  - Characterizing relapse prevention in bipolar disorder with adjunctive
      ziprasidone: clinical and methodological implications.
AB  - BACKGROUND: Ziprasidone, adjunctive to either lithium or valproate, has
      previously been shown to be associated with a significantly lower risk of relapse
      in bipolar disorder compared with lithium or valproate treatment alone. METHODS:
      This placebo-controlled outpatient trial with ziprasidone adjunctive to lithium
      or valproate or lithium and valproate alone, for subjects with a recent or
      current manic or mixed episode of bipolar I disorder, comprised a 2.5- to 4
      month, open-label stabilization period, followed by a 6-month, double-blind
      maintenance period. These post hoc analyses characterize the relapse outcomes by
      dose, relapse types and timing as well as all-reason discontinuations during the
      maintenance period. RESULTS: Time to relapse and all-reason discontinuation were
      both statistically significant in favor of the ziprasidone 120mg/day group
      compared with placebo (p=0.004 and 0.001, respectively) during the 6-month double
      blind period. There was no difference in time to relapse in the 80 and 160mg/day
      dose groups compared with placebo (p=0.16 and 0.40, respectively) and, likewise,
      for time to all-reason discontinuation (p=0.20 for both doses). The majority of
      relapses in each group occurred prior to week 8, and most were depressive in
      nature. LIMITATIONS: The primary study was not designed to compare relapse rates
      by dose groups. CONCLUSIONS: These analyses confirm the effectiveness of
      ziprasidone (80-160mg/day) in preventing relapses in subjects with bipolar
      disorder, with the 120mg/day dosage appearing to have the highest relapse
      prevention rate.

PMID- 22999895
TI  - Secondary hyperparathyroidism does not develop in patients with low 25(OH)D3
      levels: review of parathyroid hormone regulation.

PMID- 22999896
TI  - Hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with a
      Madrid II mutation.
AB  - The hypoxanthine-guanine phosphoribosyltransferase deficiency is an inborn error
      of purine metabolism, linked to the X chromosome. The clinical phenotypes
      associated with HPRT deficiency varied according to the level of enzyme
      deficiency, with a large spectrum of neurologic features like self-injurious
      behaviour in patients with complete deficiency. We report a 20-year-old man who
      had asymmetric polyarthritis, tophi, hyperuricemia, nephrolithiasis and mild
      neurologic symptoms with undetectable levels of HPRT activity in lysed
      erythrocytes. The genetic study identified the c.143G>A mutation in exon 3, GAA
      CGT (CTT>GAA CAT CTT (48arg>his). The presence of gouty arthropathy and chronic
      hyperuricemia in a young patient with neurological symptoms, suggests HPRT
      deficiency for which it is necessary its enzyme and molecular determination.

PMID- 22999897
TI  - Continuous diaphragm sign in amyopathic dermatomyositis.

PMID- 22999898
TI  - In normal knees, joint space width (JSW) is correlated with the intermargin
      distance (IMD), a measure of medial tibial plateau alignment. Variations in IMD
      explain variability in JSW in serial radiographs.
AB  - OBJECTIVE: To ascertain the importance of alignment of the medial tibial plateau
      (MTP), as determined by the distance between the anterior and posterior margins
      of the plateau (intermargin distance [IMD]), for measurements of joint space
      width (JSW) in radiographs of normal knees. METHODS: JSW and IMD were measured in
      paired baseline and 12-month knee films of 122 subjects from the osteoarthritis
      initiative (OAI). Relationships between JSW and IMD, and between the variation in
      JSW and variation in IMD, were evaluated. RESULTS: In cross-sectional analysis, a
      non-linear relationship existed between JSW and the concurrent IMD. With poor MTP
      alignment (IMD>1.7 mm), a 1.0-mm increase in IMD resulted in a 0.16-mm (95%CI:
      0.11-0.21) increase in JSW (P<0.0001). In a longitudinal analysis, the effect of
      IMD variation on variation in JSW was also highly significant (P<0.0001). A
      variation of 1 mm between IMD(Baseline) and IMD(12month) was associated with a
      0.10-mm (95% CI: 0.06-0.13) variation in JSW, with variations in JSW and IMD
      occurring in the same direction. An IMD variation less than or equal to 1.0mm was
      determined to be acceptable for accurate evaluation of JSW in serial radiographs.
      CONCLUSION: The error in measurement of JSW caused by variation in IMD in serial
      radiographs of normal knees can be as large, or larger, than the mean rate of 12
      month joint space narrowing (JSN) in OA knees. MTP alignment and replication of
      alignment in serial knee films are required for accurate determination of JSN in
      OA knee.

PMID- 22999899
TI  - Eosinophilic fasciitis with paroxysmal nocturnal hemoglobinuria.
AB  - Eosinophilic fasciitis is a rare connective tissue disorder, which can be
      associated with hematological complications in 10% of cases, such as aplastic
      anemia or acquired amegakaryocytic thrombocytopenia. Paroxysmal nocturnal
      hemoglobinuria had never been described in a patient suffering from eosinophilic
      fasciitis. We report an original case of a 59-year-old patient who developed a
      moderate aplastic pancytopenia while he was treated for a biopsy-proven
      eosinophilic fasciitis. A complete set of investigations was carried out and was
      found to be negative, including a first research of paroxysmal nocturnal
      hemoglobinuria. Two years after disease onset, while pancytopenia remained
      stable, occurrence of morning dark urine led to found a paroxysmal nocturnal
      hemoglobinuria clone. We discuss a potential link between the two conditions and
      hypothesize that paroxysmal nocturnal hemoglobinuria blood cells may pre-exist
      for a long time and take a survival advantage in the setting of marrow injury, as
      observed in eosinophilic fasciitis with hematological complications. We finally
      suggest that paroxysmal nocturnal hemoglobinuria should be included as a
      hematological complication of eosinophilic fasciitis.

PMID- 22999900
TI  - Influenza H1N1 infection in a patient with rheumatoid arthritis treated with
      tocilizumab.

PMID- 22999901
TI  - Candida albicans diskitis after body piercing in an immunocompetent patient.

PMID- 22999902
TI  - Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures
      in France based on X-rays and medical file analysis.
AB  - PURPOSE: Atypical sub-trochanteric and femoral shaft fractures have been reported
      in patients treated with bisphosphonates. Their incidence has been determined
      from registered data analysis using international codes. Therefore, the aim of
      our study was to estimate the real frequency of typical and atypical sub
      trochanteric or diaphyseal fractures, based on radiological and clinical data
      compared to registered data. METHODS: In the registers of three large French
      University Hospitals, patients identified with International Classification of
      Diseases, 10th Revision diagnosis codes for sub-trochanteric or diaphyseal
      fracture were selected. Frequencies of ordinary and atypical fractures were
      calculated after both registered data, radiological and clinical files analysis.
      RESULTS: Among the 4592 patients hospitalized for a femoral fracture over 5
      years, 574 were identified to have had a sub-trochanteric or femoral shaft
      fracture. 47.7% of the sub-trochanteric and femoral shaft fractures were
      misclassified, predominantly in the sub-trochanteric fractures subset. 12
      patients had an atypical fracture (4% of the sub-trochanteric and femoral shaft
      fractures) and 11 fractures presented radiological features of atypical
      fractures, whereas clinical files analysis revealed they were pathological or
      traumatic fractures. CONCLUSION: Atypical fractures frequency is very low.
      Because of their low frequency and the unreliability of registered databases, the
      risk of atypical fractures is very difficult to estimate retrospectively. A
      prospective study is needed to clarify the risk factors associated with these
      fractures.

PMID- 22999904
TI  - Calcinosis universalis complicating juvenile dermatomyositis: improvement after
      intravenous immunoglobulin therapy.

PMID- 22999903
TI  - A novel rabbit disc degeneration model induced by fibronectin fragment.
AB  - OBJECTIVE: To establish a novel and useful rabbit model of lumbar disc
      degeneration using microinjection of a fibronectin fragment. METHODS: Thirty-two
      rabbits underwent injection of N-terminal 30 kDa fibronectin fragment (Fn-f)
      (Group A, n=12; Group B, n=4) or phosphate buffered saline (PBS) (Group C, n=12;
      Group D, n=4) into the lumbar discs using a 32-gauge microsyringe. Two rabbits
      (Group E) with no treatment were sacrificed to examine the proteoglycan synthesis
      of neucleus pulposus (NP) using (35)S-sulfate incorporation assay. At the 4-, 8-,
      12-, and 16-week time points, the discs were examined histologically,
      radiographically and with proteoglycan synthesis. RESULTS: (1) Histology
      demonstrated a progressive loss of cell numbers in NP and architecture
      disorganization in NP and annulus fibrosus (AF) over the study period. (2)
      Radiology: comparing with the PBS-injected discs, the Fn-f-injected discs
      exhibited no significant differences in disc heights at the 4-week time point,
      but significant decreases in disc heights at the 8-, 12-, and 16-week time points
      (P<0.01). Apparent anterior osteophytes formed at the 12-week time point and
      enlarged remarkably by the 16-week time point in the Fn-f-injected spines. (3)
      Protoglycan synthesis in the Fn-f-injected discs decreased progressively
      (P<0.01). At each time point, the Fn-f-injected discs showed significantly
      decreased proteoglycan synthesis compared with controls (P<0.05 or P<0.01).
      CONCLUSIONS: Fn-f induced a progressively degenerative process in rabbit discs,
      which was consistent with the spontaneous degeneration in human. Fn-f induced
      degeneration seemed to be a novel and useful model for the study of disc
      degeneration at the molecular level.

PMID- 22999905
TI  - Favorable radiological outcome of skeletal Erdheim-Chester disease involvement
      with anakinra.
AB  - Erdheim-Chester disease is a rare non-langerhans cell histiocytosis characterized
      by infiltration of foamy CD68-positive but CD1a-negative macrophages and fibro
      inflammatory lesions as retroperitoneal, periureteral areas or bones. Interferon
      alpha therapy has been used as treatment but it had variable efficiency and
      limited tolerance. More recently, a recombinant form of interleukin-1 receptor
      antagonist (anakinra) was used with success but no skeletal radiological
      improvement was recorded. We report here a case of interleukin-1 receptor
      antagonist in the treatment of refractory bones infiltration in Erdheim-Chester
      disease. After 1 year of treatment, the positron emission tomography-computed
      tomography showed an outstanding response of the skeletal involvement with
      clearly lower and smaller hypermetabolism images.

PMID- 22999906
TI  - Plasma soluble urokinase plasminogen activator receptor (suPAR) levels in
      ankylosing spondylitis.
AB  - Recent studies demonstrated that soluble urokinase plasminogen activator receptor
      (suPAR) is a valuable marker in the recognition of an inflammatory response.
      Ongoing inflammation leads to elevated plasma suPAR levels. We aimed to
      characterize plasma suPAR levels in ankylosing spondylitis (AS) patients compared
      to healthy individuals in order to reveal if suPAR could be used as a clinical
      marker of inflammation in AS. We measured plasma suPAR and C-reactive protein
      (CRP) levels as well as erythrocyte sedimentation rate (ESR) in 33 AS patients at
      various stages of disease duration and activity and 29 healthy controls. CRP and
      ESR values were higher in AS patients than in healthy individuals, while suPAR
      values were comparable (median [interquartile range]: 2.97 [2.57-3.80] ng/mL vs.
      2.80 [2.06-3.42] ng/mL, P>0.05). In AS patients, a correlation was detected
      between BASDAI scores and CRP as well as ESR values but not suPAR levels
      (P=0.0005, r=0.57 and P=0.01, r=0.43, respectively). Unlike in many other
      inflammatory conditions, plasma suPAR levels do not reflect inflammation in AS.
      To assess the inflammatory status in AS, ESR and particularly CRP values are
      still more appropriate clinical markers. In line with earlier findings, our
      results indicate that, unlike suPAR, both of these markers are positively
      correlated with disease activity in AS.

PMID- 22999907
TI  - Two cases of Takayasu's arteritis occurring under anti-TNF therapy.
AB  - Takayasu's arteritis is a granulomatous, large vessel vasculitis that affects the
      aorta, its major branches and the pulmonary arteries. Compelling evidence exists
      to support the notion that Takayasu's arteritis is a T-cell mediated process and
      that tumor necrosis factor alpha (TNFa) is an important factor in the
      pathogenesis of this disease. Moreover, encouraging results from recent studies
      support the use of anti-TNFa therapy for relapsing or resistant cases of
      Takayasu's arteritis. Here, however, we describe the case of two patients: one
      with seropositive rheumatoid arthritis, the other with HLA-B27 negative
      spondylarthropathy, who developed Takayasu's arteritis during treatment with TNFa
      inhibitors (adalimumab and golimumab respectively). This is the first report of
      Takayasu's arteritis in rheumatic patients under TNFa blocking agents which
      suggests the presence of different pathogenetic mechanism in a subgroup of
      patients with Takayasu's arteritis, as well as a potential role of TNFa blockers
      as triggers of this disease in some cases.

PMID- 22999908
TI  - Acute hepatitis E during biotherapy.
AB  - Hepatitis E is a rare and usually asymptomatic infection. However, its incidence
      is rising in France, and it can cause severe or chronic manifestations in
      immunocompromised patients. Here, we report a case of hepatitis E in a patient
      with rheumatoid arthritis who had immunosuppression due to treatment with a
      biological agent.

PMID- 22999909
TI  - Improving agreement in assessment of synovitis in rheumatoid arthritis.
AB  - OBJECTIVE: Synovitis assessment through evaluation of swollen joints is integral
      in steering treatment decisions in rheumatoid arthritis (RA). However, there is
      high inter-observer variation. The objective was to assess if a short collegiate
      consensus would improve swollen joint agreement between rheumatologists and
      whether this was affected by experience. METHODS: Eighteen rheumatologists from
      French university rheumatology units participated in three 30 minutes rounds over
      a half day meeting evaluating joint counts of RA patients in small groups,
      followed by short consensus discussions. Agreement was evaluated at the end of
      each round as follows: (i) global agreement of swollen joints (ii) swollen joint
      agreement according to level of experience of the rheumatologist (iii) swollen
      joint count and (iv) agreement of disease activity state according to the Disease
      Activity Score (DAS28). Agreement was calculated using percentage agreement and
      kappa. RESULTS: Global agreement of swollen joints failed to improve (kappa 0.50
      to 0.52) at the joint level. Agreement between seniors did not improve but
      agreement between newly qualified rheumatologists and their senior peer, which
      was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of
      the consensus exercises. Concordance of DAS28 activity states improved from 71%
      to 87%. CONCLUSION: Consensus exercises for swollen joint assessment is
      worthwhile and may potentially improve agreement between clinicians in clinical
      synovitis and disease activity state, benefit was mostly observed in newly
      qualified rheumatologists.

PMID- 22999910
TI  - Rosuvastatin inhibits spontaneous and IL-1beta-induced interleukin-6 production
      from human cultured osteoblastic cells.
AB  - OBJECTIVE: Experimental and clinical data suggest that statins may protect bone
      by inhibiting bone resorption and/or stimulating bone formation. Interleukin-6
      (IL-6) is produced by osteoblasts, and potently stimulates osteoclast activation
      playing a key role in normal bone resorption as well as in post-menopausal and
      inflammation-driven osteoporosis. Although statins inhibit IL-6 production from
      different cell types, currently no data exist on osteoblasts. The aim of the
      study was to evaluate the effect of rosuvastatin on IL-6 production by human
      osteoblasts. METHODS: Osteoblasts from osteoarthritic patients were incubated
      with rosuvastatin (0.1-10 MUmol/L)+/-IL-1beta, and IL-6 production was evaluated
      as cytokine concentration in the culture medium (ELISA), as well as mRNA
      expression in the cells (qPCR). Putative intracellular mechanisms of the drug,
      such as blocking HMG-CoA-reductase, and interference in the prenylation process
      were investigated by the addition of mevalonate and isoprenoids. The effect of
      rosuvastatin+/-IL-1beta on the anti-resorptive molecule osteoprotegerin (OPG) was
      also assessed (ELISA). RESULTS: Rosuvastatin significantly reduced IL-6 levels in
      the osteoblast culture medium, both in unstimulated and IL-1beta-stimulated
      cells. This effect was reversed by mevalonate or geranylgeraniol, but not
      farnesol. Moreover, the drug decreased both spontaneous and IL-1beta-induced IL-6
      mRNA expression in osteoblasts. Conversely, rosuvastatin did not affect OPG
      levels in the culture medium. CONCLUSION: Our results show that rosuvastatin
      decreases IL-6 production by osteoblasts, thereby suggesting a possible
      inhibiting activity on osteoclast function in an indirect way. These data may
      provide further rationale for employing rosuvastatin to beneficially affect bone
      metabolism in post-menopausal women and possibly in inflammation-driven
      osteoporosis.

PMID- 22999912
TI  - Occurrence and geographical distribution of Canine Distemper Virus infection in
      red foxes (Vulpes vulpes) of Saxony-Anhalt, Germany.
AB  - Canine Distemper Virus (CDV) infects dogs and a variety of carnivore species. In
      Saxony-Anhalt, a federal state of Germany, 761 foxes were examined for CDV
      infection, using real-time polymerase chain reaction (PCR), in the years 2010 and
      2011. A prevalence of 30.5% was found for the whole time period without
      significant changes in prevalence between 2010 and 2011. The relative risk (RR)
      of a fox to test positive for CDV varied markedly within the area of the state
      and was significantly increased in some regions. The latter was confirmed by a
      spatial cluster test that identified a significant cluster (p<0.001) with a
      diameter of 44 km in the west of the state. To protect hounds and domestic dogs
      from CDV infection, vaccination is recommended in Saxony-Anhalt.

PMID- 22999914
TI  - Acoustic radiation force impulse elastography of breast imaging reporting and
      data system category 4 breast lesions.
AB  - INTRODUCTION: This population-based study on early breast cancer detection in
      women aimed to evaluate acoustic radiation force impulse elastography to
      differentiate BI-RADS (Breast Imaging Reporting and Data System) category 4
      lesions. METHODS: Acoustic radiation force impulse was performed on 95 patients
      with 122 BI-RADS 4 breast lesions diagnosed by conventional ultrasound. We
      calculated the area ratio of lesions by using virtual touch tissue imaging and
      gray-scale imaging. By using virtual touch tissue quantification, we calculated
      the ratio of shear wave velocity (SWV) in lesions and in surrounding glandular
      tissue at the same depth (SWV ratio). RESULTS: The mean area ratio of benign
      lesions (1.09 +/- 0.17) differed from that of the malignant lesions (1.96 +/-
      0.64; P < .001). The mean SWV ratio of benign lesions (2.44 +/- 1.27) was lower
      than that of malignant lesions (5.74 +/- 1.68; P < .001). The cutoff for the area
      and SWV ratios for malignancy were estimated to be 1.37 and 3.65, respectively.
      CONCLUSIONS: Acoustic radiation force impulse provides quantitative elasticity
      measurements, which, combined with conventional ultrasound, can potentially
      improve the diagnostic accuracy of BI-RADS 4 breast lesions, and it is helpful to
      regulate the BI-RADS classification and avoid the need for unnecessary biopsies.

PMID- 22999913
TI  - Mechanistic systems modeling to guide drug discovery and development.
AB  - A crucial question that must be addressed in the drug development process is
      whether the proposed therapeutic target will yield the desired effect in the
      clinical population. Pharmaceutical and biotechnology companies place a large
      investment on research and development, long before confirmatory data are
      available from human trials. Basic science has greatly expanded the computable
      knowledge of disease processes, both through the generation of large omics data
      sets and a compendium of studies assessing cellular and systemic responses to
      physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug
      development, mechanistic systems models can better inform target selection and
      the decision process for advancing compounds through preclinical and clinical
      research.

PMID- 22999915
TI  - Evaluation of healing processes of intraosseous defects with and without guided
      bone regeneration and platelet rich plasma. An animal study.
AB  - BACKGROUND: In most cases, the natural healing of intrabony defects only leads to
      restoration of tissue continuity without differentiation and function. However,
      repair is not regarded to be an optimal treatment method, as confirmed in many
      clinical cases. Thus it is important to choose a surgical procedure which makes
      it possible to achieve restitution ad integrum of the bone structure. The choice
      of the GBR technique is crucial, in terms of the clinical conditions and
      limitations resulting from the use of a particular material. OBJECTIVE: The
      objective of this study has been the analysis of effectiveness of selected
      surgical treatment techniques of intrabony defects in rabbits. MATERIALS AND
      METHODS: Research was conducted on 36 white rabbits. The operation technique was
      a criterion of division into 3 groups: BG/BOC (Bio-Oss Collagen((r))+Bio-Gide
      Perio((r))), BOC/PRP (Bio-Oss Collagen((r))+PRP), C (control group). Qualitative
      and quantitative histopathological evaluation was carried out after 1, 3, 6 and
      12 months. RESULTS: The highest value of the bone surface area 31.9% (SD 1.8) was
      achieved in BOC/BG group three months after the implantation, while the lowest
      was revealed in C - group - 12.5% (SD 1.32) one month following the procedure.
      CONCLUSIONS: Upon quantitative histological assessment, the bone tissue presented
      the most intensive osteogenesis within one month from the application of BOC/PRP,
      whereas this was observed after the application of BOC/BG in later stages. The
      application of two regenerative methods influenced the rate, quality and overall
      treatment of intraosseus defects.

PMID- 22999916
TI  - Acute bronchodilation increases ventilatory complexity during resting breathing
      in stable COPD: toward mathematical biomarkers of ventilatory function?
AB  - Human tidal breathing features mathematical complexity and breath-by-breath
      variability. Fluctuations in these descriptors from one state to another are
      related to the load imposed on the respiratory system. We hypothetized that
      bronchodilators would increase ventilatory complexity and variability in patients
      suffering from chronic obstructive pulmonary disease (COPD). Eleven patients with
      stable COPD (9 men; age 48-79; FEV1 42-80%; FRC above 120%) were studied before
      and after 400 MUg salbutamol. Breath-by-breath variability (coefficient of
      variation of tidal volume and breathing frequency -f) and ventilatory complexity
      (noise limit - NL, a quantifier of nonlinearity and complexity; largest Lyapunov
      exponent - LLE, an indicator of the sensitivity of the system to initial
      conditions) were described. Acute bronchodilation revealed or increased
      nonlinearity (NL 31% [20-38] to 43% [35-58], P=0.0051). Little changes in
      variability were observed (increased coefficient of variation of f). These
      observations might open new avenues toward resting breathing pulmonary function
      testing and novel respiratory biomarkers suitable for home-based lung disease
      monitoring.

PMID- 22999918
TI  - Hepatic encephalopathy with epilepsia partialis continua: a case report.

PMID- 22999917
TI  - Focal microdialysis of CO2 in the perifornical-hypothalamic area increases
      ventilation during wakefulness but not NREM sleep.
AB  - We investigated whether the perifornical-lateral hypothalamic area (PF-LHA),
      where the orexin neurons reside, is a central chemoreceptor site by microdialysis
      of artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO(2) into PF-LHA
      in conscious rats. This treatment is known to produce a focal tissue
      acidification like that associated with a 6-7 mm Hg increase in arterial
      [Formula: see text] . Such focal acidification in the PF-LHA significantly
      increased ventilation up to 15% compared with microdialysis of normal aCSF
      equilibrated with 5% CO(2) only in wakefulness but not in sleep in both the dark
      (P=0.004) and light (P<0.001) phases of the diurnal cycle. This response was
      predominantly due to a significant increase in respiratory frequency (11%,
      P<0.001). There were no significant effects on ventilation in the group with
      probes misplaced outside the PF-LHA. These results suggest that PF-LHA functions
      as a central chemoreceptor site in the central nervous system in a vigilant state
      dependent manner with predominant effects in wakefulness.

PMID- 22999919
TI  - Changes of attitudes toward epilepsy in college-preparatory high school students
      population: an indicator of global campaign successfulness?
AB  - PURPOSE: Within the "Out of the Shadows" campaign in Croatia, numerous activities
      have been organized. The aim of this study is to investigate the changes in
      knowledge and attitudes toward epilepsy in the population of college-preparatory
      high school students, and to consider whether such changes could be the result of
      these activities carried out between 2002 and 2010. METHODS: This study was
      completed in Croatia's capital city, Zagreb, and sampled adolescent college
      preparatory high school students. The surveys conducted in both 2002 and 2010
      have been evaluated and compared. In both years the examinees completed a
      questionnaire made up of identical questions concerning the students' knowledge
      and attitudes toward epilepsy. RESULTS: In total, 430 respondents (227 students
      in 2002; 203 in 2010) completed a questionnaire. The 2010 survey indicates a
      higher degree of knowledge of epilepsy amongst the students (p<0.05), as well as
      more positive attitudes related to marriage (p<0.05), and the employment of
      persons with epilepsy (PwE) (p<0.01). The percentage of positive attitudes
      related to playing with children with epilepsy was high in both surveys (>97%).
      The results for the total sample reveal that students with a better knowledge of
      epilepsy had more positive attitudes (p<0.05). Yet in the survey conducted in
      2010, when the level of factual knowledge about epilepsy was higher, this
      relationship was not possible to prove; improvement of attitudes was greater in
      students with worse knowledge of epilepsy than in those with better knowledge.
      CONCLUSION: Based on the obtained results we conclude that improvement in factual
      knowledge is only one of the factors that can induce improvement in attitudes.
      The positive changes found in Croatia most likely stem from the cumulative effect
      of the various activities conducted in accordance with the principles of the "Out
      of the Shadows" campaign.

PMID- 22999920
TI  - Complex partial seizures: going out with a hiccup.

PMID- 22999921
TI  - Neurotransmissions of antidepressant-like effects of kisspeptin-13.
AB  - Kisspeptins are G protein-coupled receptor ligands originally identified as human
      metastasis suppressor gene products that have the ability to suppress melanoma
      and breast cancer metastasis and which have recently been found to play an
      important role in initiating the secretion of gonadotropin-releasing hormone at
      puberty. In the brain, the gene is transcribed within the hippocampal dentate
      gyrus. Kisspeptin-13, one of the endogenous isoforms, consists of 13 amino acids.
      In this work, antidepressant-like effects of kisspeptin-13 were studied and the
      potential involvement of the adrenergic, serotonergic, cholinergic, dopaminergic
      and gabaergic receptors in its antidepressant-like effects was investigated in a
      modified forced swimming test (FST) in mice. The mice were pretreated with a
      nonselective alpha-adrenergic receptor antagonist, phenoxybenzamine, an
      alpha(1)/alpha(2beta)-adrenergic receptor antagonist, prazosin, an alpha(2)
      adrenergic receptor antagonist, yohimbine, a beta-adrenergic receptor antagonist,
      propranolol, a mixed 5-HT(1)/5-HT(2) serotonergic receptor antagonist,
      methysergide, a nonselective 5-HT(2) serotonergic receptor antagonist,
      cyproheptadine, a nonselective muscarinic acetylcholine receptor antagonist,
      atropine, a D(2),D(3),D(4) dopamine receptor antagonist, haloperidol, or a gamma
      aminobutyric acid subunit A receptor antagonist, bicuculline. The FST revealed
      that kisspeptin-13 reversed the immobility, climbing and swimming times,
      suggesting antidepressant-like effects. Phenoxybenzamine, yohimbine and
      cyproheptadine prevented the effects of kisspeptin-13 on the immobility, climbing
      and swimming times, whereas prazosin, propranolol, methysergide, atropine,
      haloperidol and bicuculline did not modify the effects of kisspeptin-13. The
      results demonstrated that the antidepressant-like effects of kisspeptin-13 in a
      modified mouse FST are mediated, at least in part, by an interaction of the
      alpha(2)-adrenergic and 5-HT(2) serotonergic receptors.

PMID- 22999922
TI  - The perception of verticality in lunar and Martian gravity conditions.
AB  - Although the mechanisms of neural adaptation to weightlessness and re-adaptation
      to Earth-gravity have received a lot of attention since the first human space
      flight, there is as yet little knowledge about how spatial orientation is
      affected by partial gravity, such as lunar gravity of 0.16 g or Martian gravity
      of 0.38 g. Up to now twelve astronauts have spent a cumulated time of
      approximately 80 h on the lunar surface, but no psychophysical experiments were
      conducted to investigate their perception of verticality. We investigated how the
      subjective vertical (SV) was affected by reduced gravity levels during the first
      European Parabolic Flight Campaign of Partial Gravity. In normal and
      hypergravity, subjects accurately aligned their SV with the gravitational
      vertical. However, when gravity was below a certain threshold, subjects aligned
      their SV with their body longitudinal axis. The value of the threshold varied
      considerably between subjects, ranging from 0.03 to 0.57 g. Despite the small
      number of subjects, there was a significant positive correlation of the threshold
      with subject age, which calls for further investigation.

PMID- 22999923
TI  - R280T mutation of p53 gene promotes proliferation of human glioma cells through
      GSK-3beta/PTEN pathway.
AB  - p53 mutation is associated with "gain-of-function" capabilities of human cancers.
      We aim to identify p53 mutations in human glioma cells and to explore the
      potential mechanism for mutant p53-promoted cellular growth. Whole genomic DNA
      was isolated from SWO-38, a human glioma cell line and amplified for the region
      of exons 5, 6, and 8 in p53 gene using polymerase chain reaction (PCR). By means
      of direct sequencing of PCR products and alignment analysis using BLAST database,
      a mutation of G to C transition at codon 280 of p53 exon 8 (AGA->ACA), i.e. R280T
      was detected in SWO-38 cells. Knockdown of R280T mutant p53 by RNA interference
      inhibited the GSK-3beta/PTEN associated cell proliferation, and PI3K/Akt but not
      Wnt/beta-catenin signaling pathway was involved in this process. Furthermore,
      depletion or overexpression of PTEN alone did not affect cell proliferation and
      cell cycle, implicating the impairment of PTEN function in SWO-38 cells. However,
      knockdown of both PTEN and p53 mutation could significantly rescue the p53
      depletion-mediated growth inhibition, suggesting that the R280T mutation in
      glioma may promote the proliferation through an underlying mechanism related to
      PTEN. Our observations indicate that the R280T mutation of p53 regulates the
      proliferation of human glioma cells related to the GSK-3beta/PTEN pathway. These
      findings provide valuable insights for better understanding the molecular
      mechanism of uncontrolled growth of glioma cells.

PMID- 22999924
TI  - Neuronal calcium sensor-1 and cocaine addiction: a genetic association study in
      African-Americans and European Americans.
AB  - Genes involved in drug reward pathways are plausible candidates for
      susceptibility to substance use disorders. Given the prominent role of dopamine
      in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the
      neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role
      in the pathophysiology of cocaine addiction (CA). In this study, we investigated
      whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs
      (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and
      rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African
      descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611,
      rs1342043) was attempted using a replication sample of African American (AA)
      ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry
      (cases n = 336, controls n = 656). Secondary sex specific analysis was also
      carried out for each SNP in both AA and EA individuals. Genotyping of the
      discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as
      well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA
      in AAs; however, this marker could not be confirmed in either the AA or EA
      replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043
      showed a significant association with CA (genotypic p = 0.0001, allelic p =
      0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p =
      0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to
      susceptibility of CA in individuals of African descent.

PMID- 22999925
TI  - Choline acetyltransferase expression in rat prefrontal cortex and hippocampus
      after acute and chronic exposure to amisulpride, haloperidol, and risperidone.
AB  - Recently, there has been an increasing concern that atypical antipsychotics as
      well as typical ones may cause detrimental effects on cognitive function.
      Supporting evidence comes from many preclinical studies demonstrating that long
      term administration of haloperidol, risperidone, and ziprasidone reduced choline
      acetyltransferase (ChAT) expression in rat hippocampus (HIP). However, to the
      best of our knowledge, no studies have examined the effects of amisulpride on
      ChAT expression in rats. Therefore, the aim of this study was to investigate the
      effects of acute and chronic administration of amisulpride, haloperidol, and
      risperidone on ChAT expression in the rat prefrontal cortex (PFC) and HIP.
      Animals received daily intraperitoneal (i.p.) injections of amisulpride (5 or
      100mg/kg), haloperidol (1 or 2mg/kg), risperidone (1 or 2mg/kg) or vehicle for 7
      or 45 days. One day after the last injection, rats were sacrificed. ChAT
      immunoreactivity was assessed with immunofluorescence staining. Target areas of
      brain were PFC and HIP (CA1, CA3 and DG). The short-term administration of
      haloperidol and risperidone produced significant decrease of ChAT
      immunoreactivity in the PFC and HIP compared to vehicle whereas amisulpride had
      no effects on ChAT immunoreactivity in the PFC and HIP. In long-term study,
      haloperidol and risperidone decreased ChAT-positive cells and/or fiber pixel
      density in the PFC and HIP whereas amisulpride decreased ChAT-positive cells in
      the PFC and had no effects on fiber pixel density of ChAT in the HIP. The results
      suggest that both short-term and long-term administration of haloperidol and
      risperidone, and long-term administration of amisulpride may produce detrimental
      effects on cognitive function by reducing ChAT expression in the PFC and/or HIP.

PMID- 22999926
TI  - Treadmill rehabilitation treatment enhanced BDNF-TrkB but not NGF-TrkA signaling
      in a mouse intracerebral hemorrhage model.
AB  - Intracerebral hemorrhage (ICH), accounting for 15-20% of strokes, can cause
      significant brain injury and life long neurological deficits. We investigated
      whether treadmill exercise rehabilitation could improve brain repair after ICH
      and whether involvement of NFG-TrkA and BDNF-TrkB signaling could be observed
      during repair period in an experimental mouse ICH model reproduced by heparinized
      collagenase infusion into the left caudate putamen. 5-Bromo-2-deoxyuridine (BrdU)
      labeled new dividing cell can be observed clearly around the injured cortex and
      striatum region on day 7 (D7) after operation, and both TrkA and TrkB neurotropic
      receptors were activated. A subgroup of these ICH mice began the treadmill
      exercise from D4 after operation. Then we found that the overall
      immunofluorescent signals of p-Y490-TrkA and p-Y705-TrkB were both decreased in
      all groups at D14 after operation. However, compared to the non-exercise ICH
      group mouse, the immunofluorescent intensity of BDNF and p-Y705-TrkB were
      significantly higher in the exercise group. In addition, there was no difference
      in p-Y490-TrkA. Our results suggest that BDNF-TrkB but not NGF-TrkA signaling is
      involved in the brain repair after ICH, and early proper treadmill exercise might
      promote this repair process.

PMID- 22999928
TI  - Nerve injury causes long-term attentional deficits in rats.
AB  - Human chronic pain sufferers frequently report problems with attention and
      concentration that affect daily functioning and quality of life. Chronic pain is
      also commonly associated with anxiety and depression. It is currently not known
      if the pain causes these co-morbidities, or if they are pre-disposing risk
      factors for the development of chronic pain. Animal studies suggest a possible
      causative effect of pain on cognition, but usually tests are conducted during
      acute ongoing pain when the pain may act as a distracter to normal cognitive and
      emotional processing. Here we examine long-term effects of nerve injury on
      cognitive functioning in a rat model, which contributes to better understanding
      of the relationship between cognitive impairment and chronic pain experience in
      human populations. This study investigated attentional capability, anxiety-like
      behavior and sensory functioning 6 months after spared nerve injury (SNI) surgery
      a time-point well beyond the acute pain phase and akin to decades of pain
      experience in humans. Male Long Evans rats subjected to nerve injury remained
      hypersensitive to sensory stimuli from the time of injury to the 6-month post
      injury assessment. At 6 months they were impaired on a visual non-selective, non
      sustained attention task and displayed anxiety-like behaviors in the elevated
      plus maze. These findings show that cognitive disturbances observed during acute
      pain persist for months in a rodent chronic pain model and suggest that cognitive
      alterations in chronic pain patients are at least partially caused by the chronic
      pain state.

PMID- 22999927
TI  - Altered atrial neurotransmitter release in transgenic p75(-/-) and gp130 KO mice.
AB  - Heart rate is controlled by stimulatory sympathetic and inhibitory
      parasympathetic nerves innervating the sino-atrial node and cardiac conduction
      system. Sympathetic release of norepinephrine (NE) and parasympathetic release of
      acetylcholine (ACh) are controlled by the central nervous system, and by pre
      synaptic inhibition of transmitter release within the atria. An increase in
      cardiac sympathetic transmission relative to parasympathetic transmission is
      pathological as it can lead to disturbances in heart rhythm, catecholaminergic
      toxicity and development of arrhythmias or fibrillation. Mice lacking the p75
      neurotrophin receptor (p75(-/-)) have elevated atrial NE but a low heart rate
      suggesting autonomic dysregulation. Similarly, mice whose sympathetic neurons
      lack the gp130 cytokine receptor (gp130 KO) have a normal heart rate but enhanced
      bradycardia after vagal nerve stimulation. What is unclear is whether cardiac
      autonomic disturbances in these animals reflect systemic alterations in nerve
      activity or whether localized defects in neurotransmitter stores or release are
      involved. To examine local stimulus-evoked release of neurotransmitters, we have
      developed a novel method for simultaneous quantification of both NE and ACh after
      ex vivo atrial field stimulation. Using HPLC with electrochemical detection for
      NE, and HPLC with mass spectrometry for ACh, we found that following field
      stimulation NE release was impaired in p75(-/-) atria while ACh content and
      release was elevated in gp130 KO atria. Thus, alterations in localized
      transmitter release from atrial explants are consistent with in vivo deficits in
      heart rate control, suggesting peripheral alterations in autonomic transmission
      in these mice.

PMID- 22999929
TI  - Protection by silibinin against experimental ischemic stroke: up-regulated pAkt,
      pmTOR, HIF-1alpha and Bcl-2, down-regulated Bax, NF-kappaB expression.
AB  - Inflammation and apoptosis play an important role in cerebral ischemic
      pathogenesis and may represent a target for treatment. Silibinin has been proved
      to elicit a variety of biological effects through its anti-inflammatory and anti
      apoptotic properties in hepatotoxic, cancer and carcinogenic events. Whether this
      protective effect applies to ischemic injury in brain is still unknown, we
      therefore investigated the potential protective role of silibinin in ischemic
      stroke and the underlying mechanisms. Silibinin was administered intragastric 30
      min before permanent middle cerebral artery occlusion (pMCAO). We found that
      silibinin significantly alleviated neurological deficit, reduced infarct volume,
      and suppressed brain edema, which were accompanied with upregulation of pAkt,
      pmTOR, HIF-1alpha, Bcl-2 and downregulation of Bax, NF-kappaB in ischemic brain
      tissue after stroke. Our results show that silibinin might exert anti
      inflammatory and anti-apoptotic effects in ischemic brain through activating
      Akt/mTOR signaling.

PMID- 22999930
TI  - miR-124 regulates neural stem cells in the treatment of spinal cord injury.
AB  - Several studies demonstrated that the overexpression of miR-124 in neural stem
      cells (NSCs) could lead the NSCs to differentiate into neurons and astrocytes,
      which may be important for functional recovery in spinal cord injury. The present
      study attempted to explore the potential repairing effect of the NSCs transfected
      with miR-124 for the rats with spinal cord injury (SCI). NSCs transfected with
      miR-124 were transplanted into rats by intravenous injection after SCI. The
      effects of miR-124 on the differentiation of NSCs and the treatment for the SCI
      model rats were experimentally investigated. The reduction of cavity volume in
      focal lesions and Basso-Beattie-Bresnahan (BBB) scores were used as the criteria
      of functional recovery of the SCI-model rats. Up-regulation of miR-124 promoted
      the differentiation of NSCs. Transfection of miR-124 in NSCs dramatically
      increased the percentage of NeuN-positive cells, and reduced the percentage of
      GFAP-positive cells in vitro and in vivo respectively. All of the rats treated
      with NSCs transfected with miR-124 achieved the better functional recovery than
      the ones in NSCs and sham control groups. Furthermore, the systemic delivery of
      the NSCs transfected with miR-124 resulted in a reduction of lesion cavity volume
      of SCI-model rats. Thus, Overexpression of miR-124 can promote the
      differentiation of NSCs and play an important role in the repair of SCI. The
      utility of intravenous delivery of stem cells regulated with miR-124 to target
      lesion areas as a prospective therapeutic approach in acute spinal cord injury is
      very promising in the future.

PMID- 22999931
TI  - Protein kinase Ceta polymorphism and the susceptibilities to intracerebral
      hemorrhage in the Taiwan population.
AB  - Protein kinase Ceta (PRKCH) 1425G/A polymorphism has been suggested to be a
      susceptible genetic locus of stroke by genome-wide polymorphism analysis with
      several replication reports in the Asian populations. While this association was
      found to exist in the stroke subtype of lacunar infarction especially, the
      susceptibility of this genetic variant to the intracerebral hemorrhage (ICH)
      subtypes is unknown to date. This study examined the associations of PRKCH
      1425G/A with ICH as well as the stratification of ICH subtypes in the Taiwan
      population. Genotyping was determined by PCR-based restriction and single strand
      conformation polymorphism for 381 controls and 303 ICH patients, including 266
      deep ICH and 37 lobar ICH patients. Multivariable logistic regression was used to
      analyze the associations of PRKCH genotypes with stroke subtypes under dominant
      models. Covariables including age, sex, hypertension, diabetes mellitus, and
      total cholesterol level were analyzed to delineate the independency of
      associations. To account for the multiple testing, permutation testing of 1000
      replicates was performed for empirical estimates. Distribution of the genotypes
      of PRKCH 1425G/A was similar while comparing controls (GG: 61%, GA: 33.3%, and
      AA: 5.7%) with the total ICH group (GG: 57.8%, GA: 36.6%, and AA: 5.6%, p=0.68)
      and the deep ICH group (GG: 60.2%, GA: 34.2%, and AA: 5.6%, p=0.99). Distribution
      differ between controls and lobar ICH (GG: 40.5%, GA: 54.1%, and AA: 5.4%,
      p=0.04). Multivariable logistic regression adjusting for age and sex showed a
      significant association of PRKCH 1425G/A with lobar ICH risks in a dominant model
      (OR=2.4, 95% confidence interval (CI) 1.2 to 4.7, p=0.012). When additionally
      adjusting for hypertension and cholesterol level, this association remained
      significant (OR=2.4, 95% CI 1.1 to 5.5, p=0.029). There was a borderline
      association of minor allele A with lobar ICH when compared with controls
      (OR=1.73, 95% CI 1.01 to 2.9, p=0.039). The variation was not associated with
      deep ICH. In conclusion, PRKCH 1425G/A variant was not a risk locus for deep ICH
      phenotype. PRKCH 1425G/A to the susceptibility of lobar ICH shown in this report
      needs further replication.

PMID- 22999932
TI  - Methotrexate suspension before pregnancy.

PMID- 22999933
TI  - Regulating contractility of the actomyosin cytoskeleton by pH.
AB  - The local interaction of F-actin with myosin-II motor filaments and crosslinking
      proteins is crucial for the force generation, dynamics, and reorganization of the
      intracellular cytoskeleton. By using a bottom-up approach, we are able to show
      that the contractility of reconstituted active actin systems is tightly
      controlled by the local pH. The pH-dependent intrinsic crossbridge strength of
      myosin-II is identified to account for a sharp transition of the actin/myosin-II
      activity from noncontractile to contractile by a change in pH of only 0.1. This
      pH-dependent contractility is a generic feature, which is observed in all studied
      crosslinked actin/myosin-II systems. The specific type and concentration of
      crosslinking protein allows one to sensitively adjust the range of pH where
      contraction occurs, which can recover the behavior found in Xenopus laevis oocyte
      extracts. Small variations in pH provide a mechanism of controlling the
      contractility of cytoskeletal structures, which can be expected to have broad
      implications in our understanding of cytoskeletal regulation.

PMID- 22999934
TI  - Three distinct patterns of histone H3Y41 phosphorylation mark active genes.
AB  - The JAK2 tyrosine kinase is a critical mediator of cytokine-induced signaling. It
      plays a role in the nucleus, where it regulates transcription by phosphorylating
      histone H3 at tyrosine 41 (H3Y41ph). We used chromatin immunoprecipitation
      coupled to massively parallel DNA sequencing (ChIP-seq) to define the genome-wide
      pattern of H3Y41ph in human erythroid leukemia cells. Our results indicate that
      H3Y41ph is located at three distinct sites: (1) at a subset of active promoters,
      where it overlaps with H3K4me3, (2) at distal cis-regulatory elements, where it
      coincides with the binding of STAT5, and (3) throughout the transcribed regions
      of active, tissue-specific hematopoietic genes. Together, these data extend our
      understanding of this conserved and essential signaling pathway and provide
      insight into the mechanisms by which extracellular stimuli may lead to the
      coordinated regulation of transcription.

PMID- 22999935
TI  - Memory deficits induced by inflammation are regulated by alpha5-subunit
      containing GABAA receptors.
AB  - Systemic inflammation causes learning and memory deficits through mechanisms that
      remain poorly understood. Here, we studied the pathogenesis of memory loss
      associated with inflammation and found that we could reverse memory deficits by
      pharmacologically inhibiting alpha5-subunit-containing gamma-aminobutyric acid
      type A (alpha5GABA(A)) receptors and deleting the gene associated with the alpha5
      subunit. Acute inflammation reduces long-term potentiation, a synaptic correlate
      of memory, in hippocampal slices from wild-type mice, and this reduction was
      reversed by inhibition of alpha5GABA(A) receptor function. A tonic inhibitory
      current generated by alpha5GABA(A) receptors in hippocampal neurons was increased
      by the key proinflammatory cytokine interleukin-1beta through a p38 mitogen
      activated protein kinase signaling pathway. Interleukin-1beta also increased the
      surface expression of alpha5GABA(A) receptors in the hippocampus. Collectively,
      these results show that alpha5GABA(A) receptor activity increases during
      inflammation and that this increase is critical for inflammation-induced memory
      deficits.

PMID- 22999936
TI  - Role of unusual P loop ejection and autophosphorylation in HipA-mediated
      persistence and multidrug tolerance.
AB  - HipA is a bacterial serine/threonine protein kinase that phosphorylates targets,
      bringing about persistence and multidrug tolerance. Autophosphorylation of
      residue Ser150 is a critical regulatory mechanism of HipA function. Intriguingly,
      Ser150 is not located on the activation loop, as are other kinases; instead, it
      is in the protein core, where it forms part of the ATP-binding "P loop motif."
      How this buried residue is phosphorylated and regulates kinase activity is
      unclear. Here, we report multiple structures that reveal the P loop motif's
      exhibition of a remarkable "in-out" conformational equilibrium, which allows
      access to Ser150 and its intermolecular autophosphorylation. Phosphorylated
      Ser150 stabilizes the "out state," which inactivates the kinase by disrupting the
      ATP-binding pocket. Thus, our data reveal a mechanism of protein kinase
      regulation that is vital for multidrug tolerance and persistence, as kinase
      inactivation provides the critical first step in allowing dormant cells to revert
      to the growth phenotype and to reinfect the host.

PMID- 22999937
TI  - Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney
      development.
AB  - Multipotent stem cells and their lineage-restricted progeny drive nephron
      formation within the developing kidney. Here, we document expression of the adult
      stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor
      identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and
      localization of Lgr5(+ve) cells coincided with that of the S-shaped body around
      embryonic day 14. Lgr5 expression remained restricted to cell clusters within
      developing nephrons in the cortex until postnatal day 7, when expression was
      permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a
      stem/progenitor population within nascent nephrons dedicated to generating the
      thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5
      surface marker and experimental models described here will be invaluable for
      deciphering the contribution of early nephron stem cells to developmental defects
      and for isolating human nephron progenitors as a prerequisite to evaluating their
      therapeutic potential.

PMID- 22999938
TI  - TET1 suppresses cancer invasion by activating the tissue inhibitors of
      metalloproteinases.
AB  - Tumor suppressor gene silencing through cytosine methylation contributes to
      cancer formation. Whether DNA demethylation enzymes counteract this oncogenic
      effect is unknown. Here, we show that TET1, a dioxygenase involved in cytosine
      demethylation, is downregulated in prostate and breast cancer tissues. TET1
      depletion facilitates cell invasion, tumor growth, and cancer metastasis in
      prostate xenograft models and correlates with poor survival rates in breast
      cancer patients. Consistently, enforced expression of TET1 reduces cell invasion
      and breast xenograft tumor formation. Mechanistically, TET1 suppresses cell
      invasion through its dioxygenase and DNA binding activities. Furthermore, TET1
      maintains the expression of tissue inhibitors of metalloproteinase (TIMP) family
      proteins 2 and 3 by inhibiting their DNA methylation. Concurrent low expression
      of TET1 and TIMP2 or TIMP3 correlates with advanced node status in clinical
      samples. Together, these results illustrate a mechanism by which TET1 suppresses
      tumor development and invasion partly through downregulation of critical gene
      methylation.

PMID- 22999939
TI  - Crosstalk of humoral and cell-cell contact-mediated signals in postnatal body
      growth.
AB  - The growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis mediates
      postnatal body growth. The GH receptor has been regarded as the sole receptor
      that mediates the Janus kinase 2 (JAK2)/signal transducers and activators of the
      transcription 5B (STAT5B) signal toward IGF1 synthesis. Here, we report a
      signaling pathway that regulates postnatal body growth through EphA4, a member of
      the Eph family of receptor tyrosine kinases and a mediator of the cell-cell
      contact-mediated signaling. EphA4 forms a complex with the GH receptor, JAK2, and
      STAT5B and enhances Igf1 expression predominantly via the JAK2-dependent pathway,
      with some direct effect on STAT5B. Mice with a defective Epha4 gene have a gene
      dose-dependent short stature and low plasma IGF1 levels. Igf1 messenger RNA
      (mRNA) in the liver and many other tissues was also significantly reduced in
      Epha4-knockout mice, whereas pituitary Gh mRNA and plasma GH levels were not.
      These findings suggest that the local cell-cell contact-mediated ephrin/EphA4
      signal is as important as the humoral GH signal in IGF1 synthesis and body size
      determination.

PMID- 22999940
TI  - High-throughput screening for bioactive molecules using primary cell culture of
      transgenic zebrafish embryos.
AB  - Transgenic zebrafish embryos expressing tissue-specific green fluorescent protein
      (GFP) can provide an unlimited supply of primary embryonic cells. Agents that
      promote the differentiation of these cells may be beneficial for therapeutics. We
      report a high-throughput approach for screening small molecules that regulate
      cell differentiation using lineage-specific GFP transgenic zebrafish embryonic
      cells. After validating several known regulators of the differentiation of
      endothelial and other cell types, we performed a screen for proangiogenic
      molecules using undifferentiated primary cells from flk1-GFP transgenic zebrafish
      embryos. Cells were grown in 384-well plates with 12,128 individual small
      molecules, and GFP expression was analyzed by means of an automated imaging
      system, which allowed us to screen thousands of compounds weekly. As a result, 23
      molecules were confirmed to enhance angiogenesis, and 11 of them were validated
      to promote the proliferation of mammalian human umbilical vascular endothelial
      cells and induce Flk1+ cells from murine embryonic stem cells. We demonstrated
      the general applicability of this strategy by analyzing additional cell lineages
      using zebrafish expressing GFP in pancreatic, cardiac, and dopaminergic cells.

PMID- 22999941
TI  - Combating cancer predisposition in association with idiopathic immune deficiency:
      a recurrent nodal and cutaneous T-cell lymphoproliferative disease in a patient
      with cartilage-hair hypoplasia.

PMID- 22999942
TI  - Comparison of autologous hematopoietic cell transplantation and chemotherapy as
      postremission treatment in non-M3 acute myeloid leukemia in first complete
      remission.
AB  - Randomized trials of acute myeloid leukemia (AML) in first complete remission
      (CR1) showed that autologous hematopoietic cell transplantation (auto-HCT)
      improves relapse-free survival (RFS) but not overall survival (OS), compared with
      chemotherapy. Using a database of 2518 adult patients with AML in CR1, we
      conducted a 5-month landmark analysis and found that auto-HCT improves 3-year RFS
      but not OS compared with chemotherapy. INTRODUCTION: A number of randomized
      trials in patients with AML in CR1 have been conducted and they showed that auto
      HCT improves RFS but not OS, compared with chemotherapy. However, because these
      trials have had compliance problems, the value of auto-HCT still has not been
      clearly established. PATIENTS AND METHODS: Using a database of 2518 adult
      patients with AML in CR1, we retrospectively analyzed the outcome of auto-HCT and
      compared it with intensive nonmyeloablative chemotherapy using landmark analyses.
      RESULTS: In 103 auto-HCT recipients, OS and RFS at 3 years from treatment were
      65% and 57%, respectively. Multivariate analysis showed that unfavorable risk
      cytogenetics and entry into CR1 after 2 courses of induction treatment predicted
      a poor outcome. Because the median time interval between CR1 and auto-HCT was 153
      days, landmark analyses at 5 months after CR1 were performed to compare 1290
      patients who received chemotherapy alone (median age, 52 years; range, 16-70)
      with 103 who received auto-HCT (median age, 48 years; range, 16-67). Auto-HCT
      improves 3-year RFS (58% vs. 37%; P < .001) but not OS compared with chemotherapy
      alone. Among patients with unfavorable risk cytogenetics or those who required 2
      courses to reach CR1, there was no significant difference in RFS between the 2
      groups. CONCLUSION: Auto-HCT can be considered as a postremission therapy for AML
      patients with favorable or intermediate risk cytogenetics who achieve CR1 after a
      single course of induction treatment.

PMID- 22999943
TI  - Autoimmune manifestations in large granular lymphocyte leukemia.
AB  - Large granular lymphocyte (LGL) leukemia features a group of indolent
      lymphoproliferative diseases that display a strong association with various
      autoimmune conditions. Notwithstanding, these autoimmune conditions have not been
      comprehensively characterized or systematized to date. As a result, their
      clinical implications remain largely unknown. The authors offer a comprehensive
      review of the existing literature on various autoimmune conditions documented in
      the course of T-cell LGL (T-LGL) leukemia. Though some of them are thought be
      secondary to the LGL leukemia, others could be primary and might even play a role
      in its pathogenesis. A considerable clinico-laboratory overlap between T-LGL
      leukemia associated with rheumatoid arthritis and Felty's syndrome suggests that
      they are just different eponyms for the same clinical entity.

PMID- 22999944
TI  - Redefining the viral reservoirs that prevent HIV-1 eradication.
AB  - This Perspective proposes definitions for key terms in the field of HIV-1 latency
      and eradication. In the context of eradication, a reservoir is a cell type that
      allows persistence of replication-competent HIV-1 on a timescale of years in
      patients on optimal antiretroviral therapy. Reservoirs act as a barrier to
      eradication in the patient population in which cure attempts will likely be made.
      Halting viral replication is essential to eradication, and definitions and
      criteria for assessing whether this goal has been achieved are proposed. The cell
      types that may serve as reservoirs for HIV-1 are discussed. Currently, only
      latently infected resting CD4(+) T cells fit the proposed definition of a
      reservoir, and more evidence is necessary to demonstrate that other cell types,
      including hematopoietic stem cells and macrophages, fit this definition. Further
      research is urgently required on potential reservoirs in the gut-associated
      lymphoid tissue and the central nervous system.

PMID- 22999945
TI  - Innate immune recognition of HIV-1.
AB  - In contrast to the extraordinary body of knowledge gained over the past three
      decades on the virology, pathogenesis, and immunology of HIV-1 infection, innate
      sensors that detect HIV-1 had remained elusive until recently. By virtue of
      integration, retroviridae makes up a substantial portion of our genome. Thus,
      immune strategies that deal with endogenous retroviruses are, by necessity, those
      of self-preservation and not of virus elimination. Some of the principles of such
      strategies may also apply for defense against exogenous retroviruses including
      HIV-1. Here, I highlight several sensors that have recently been revealed to be
      capable of recognizing distinct features of HIV-1 infection, while taking into
      account the host-retrovirus relationship that converges on avoiding pathogenic
      inflammatory consequences.

PMID- 22999946
TI  - Intrinsic cellular defenses against human immunodeficiency viruses.
AB  - Viral infections are often detrimental to host survival and reproduction.
      Consequently, hosts have evolved a variety of mechanisms to defend themselves
      against viruses. A component of this arsenal is a set of proteins, termed
      restriction factors, which exhibit direct antiviral activity. Among these are
      several classes of proteins (APOBEC3, TRIM5, Tetherin, and SAMHD1) that inhibit
      the replication of human and simian immunodeficiency viruses. Here, we outline
      the features, mechanisms, and evolution of these defense mechanisms. We also
      speculate on how restriction factors arose, how they might interact with the
      conventional innate and adaptive immune systems, and how an understanding of
      these intrinsic cellular defenses might be usefully exploited.

PMID- 22999947
TI  - Human antibodies that neutralize HIV-1: identification, structures, and B cell
      ontogenies.
AB  - Antibodies that neutralize diverse strains of HIV-1 develop in ~20% of HIV-1
      infected individuals, and isolation and structural characterization of these
      antibodies are revealing how they recognize the envelope glycoprotein spike.
      Broadly reactive neutralizing antibodies utilize just a few sites of spike
      vulnerability and converge on select modes of recognition. These antibodies have
      unusual features: uncommonly long complementarity-determining loops, extensive
      somatic mutation, or both. Recent advances in next-generation sequencing of
      antibody-gene transcripts are providing genetic records of the development of
      neutralizing antibodies. These records inform an understanding of the naive B
      cell repertoire, of somatic mutation, and of the resulting antibody features that
      are critical to effective HIV-1 neutralization; based on these, we propose an
      ontogeny and structure-based system of antibody classification. The human immune
      system is capable of developing antibodies that broadly neutralize HIV-1--and an
      increasingly detailed view is accumulating for how effective immunity against HIV
      1 can be generated.

PMID- 22999949
TI  - Regulatory T cell differentiation: turning harmful into useful.
AB  - In this issue of Immunity, Lee et al. (2012) demonstrate a surprisingly broad
      "window of opportunity" for regulatory T (Treg) cell induction and provide
      evidence for an avidity model of Treg cell differentiation versus deletion.

PMID- 22999950
TI  - Treg cells acquire new directions, cytokines navigate.
AB  - Foxp3(+) Treg cells express transcription factors normally expressed by specific
      T helper cells at sites of inflammation. In this issue of Immunity, Koch et al.
      (2012) and Hall et al. (2012) demonstrate that IFN-gamma and IL-27 distinctly
      induces T-bet(+) Treg cells via STAT-1 transcription factor activation.

PMID- 22999948
TI  - HIV and HLA class I: an evolving relationship.
AB  - Successful vaccine development for infectious diseases has largely been achieved
      in settings where natural immunity to the pathogen results in clearance in at
      least some individuals. HIV presents an additional challenge in that natural
      clearance of infection does not occur, and the correlates of immune protection
      are still uncertain. However, partial control of viremia and markedly different
      outcomes of disease are observed in HIV-infected persons. Here, we examine the
      antiviral mechanisms implicated by one variable that has been consistently
      associated with extremes of outcome, namely HLA class I alleles, and in
      particular HLA-B, and examine the mechanisms by which this modulation is likely
      to occur and the impact of these interactions on evolution of the virus and the
      host. Studies to date provide evidence for both HLA-dependent and epitope
      dependent influences on viral control and viral evolution and have important
      implications for the continued quest for an effective HIV vaccine.

PMID- 22999951
TI  - Indiscriminate memories during infection control.
AB  - In this issue of Immunity, Soudja et al. (2012) demonstrate that non-antigen
      specific stimulation evoked by a variety of pathogens plays an important role in
      the innate acquisition of effector function by memory CD8(+) T cells.

PMID- 22999952
TI  - Fat chance: not much against NKT cells.
AB  - Obesity-induced inflammation contributes to multiple metabolic diseases. In this
      issue of Immunity, Lynch et al. (2012) show that invariant natural killer T
      (iNKT) cells are enriched in adipose tissue and induce anti-inflammatory pathways
      to confer protection against obesity.

PMID- 22999953
TI  - Oxysterol gradient generation by lymphoid stromal cells guides activated B cell
      movement during humoral responses.
AB  - 7alpha,25-dihydroxycholesterol (7alpha,25-OHC) is a ligand for the G protein
      coupled receptor EBI2; however, the cellular sources of this oxysterol are
      undefined. 7alpha,25-OHC is synthesized from cholesterol by the stepwise actions
      of two enzymes, CH25H and CYP7B1, and is metabolized to a 3-oxo derivative by
      HSD3B7. We showed that all three enzymes control EBI2 ligand concentration in
      lymphoid tissues. Lymphoid stromal cells were the main CH25H- and CYP7B1
      expressing cells required for positioning of B cells, and they also mediated
      7alpha,25-OHC inactivation. CH25H and CYP7B1 were abundant at the follicle
      perimeter, whereas CH25H expression by follicular dendritic cells was repressed.
      CYP7B1, CH25H, and HSD3B7 deficiencies each resulted in defective T cell
      dependent plasma cell responses. These findings establish that CYP7B1 and HSD3B7,
      as well as CH25H, have essential roles in controlling oxysterol production in
      lymphoid tissues, and they suggest that differential enzyme expression in stromal
      cell subsets establishes 7alpha,25-OHC gradients required for B cell responses.

PMID- 22999955
TI  - Deactivation of the E. coli pH stress sensor CadC by cadaverine.
AB  - At acidic pH and in the presence of lysine, the pH sensor CadC activates
      transcription of the cadBA operon encoding the lysine/cadaverine antiporter CadB
      and the lysine decarboxylase CadA. In effect, these proteins contribute to acid
      stress adaptation in Escherichia coli. cadBA expression is feedback inhibited by
      cadaverine, and a cadaverine binding site is predicted within the central cavity
      of the periplasmic domain of CadC on the basis of its crystallographic analysis.
      Our present study demonstrates that this site only partially accounts for the
      cadaverine response in vivo. Instead, evidence for a second, pivotal binding site
      was collected, which overlaps with the pH-responsive patch of amino acids located
      at the dimer interface of the periplasmic domain. The temporal response of the E.
      coli Cad module upon acid shock was measured and modeled for two CadC variants
      with mutated cadaverine binding sites. These studies supported a cascade-like
      binding and deactivation model for the CadC dimer: binding of cadaverine within
      the pair of central cavities triggers a conformational transition that exposes
      two further binding sites at the dimer interface, and the occupation of those
      stabilizes the inactive conformation. Altogether, these data represent a striking
      example for the deactivation of a pH sensor.

PMID- 22999954
TI  - Enthalpic barriers dominate the folding and unfolding of the human Cu, Zn
      superoxide dismutase monomer.
AB  - The rate-limiting step in the formation of the native dimeric state of human Cu,
      Zn superoxide dismutase (SOD1) is a very slow monomer folding reaction that
      governs the lifetime of its unfolded state. Mutations at dozens of sites in SOD1
      are known to cause a fatal motor neuron disease, amyotrophic lateral sclerosis,
      and recent experiments implicate the unfolded state as a source of soluble
      oligomers and histologically observable aggregates thought to be responsible for
      toxicity. To determine the thermodynamic properties of the transition state
      ensemble (TSE) limiting the folding of this high-contact-order beta-sandwich
      motif, we performed a combined thermal/urea denaturation thermodynamic/kinetic
      analysis. The barriers to folding and unfolding are dominated by the activation
      enthalpy at 298 K and neutral pH; the activation entropy is favorable and reduces
      the barrier height for both reactions. The absence of secondary structure
      formation or large-scale chain collapse prior to crossing the barrier for folding
      led to the conclusion that dehydration of nonpolar surfaces in the TSE is
      responsible for the large and positive activation enthalpy. Although the
      activation entropy favors the folding reaction, the transition from the unfolded
      state to the native state is entropically disfavored at 298 K. The opposing
      entropic contributions to the free energies of the TSE and the native state
      during folding provide insights into structural properties of the TSE. The
      results also imply a crucial role for water in governing the productive folding
      reaction and enhancing the propensity for the aggregation of SOD1.

PMID- 22999956
TI  - Serine phosphorylation suppresses huntingtin amyloid accumulation by altering
      protein aggregation properties.
AB  - Aggregation of expanded polyglutamine repeat-containing fragments of the
      huntingtin (htt) protein may play a key role in Huntington's disease. Consistent
      with this hypothesis, two Ser-to-Asp mutations in the 17-amino-acid N-terminal
      htt(NT) segment abrogate both visible brain aggregates and disease symptoms in a
      full-length Q(97) htt mouse model while compromising aggregation kinetics and
      aggregate morphology in an htt fragment in vitro [Gu et al. (2009). Serines 13
      and 16 are critical determinants of full-length human mutant huntingtin induced
      disease pathogenesis in HD mice. Neuron64, 828-840]. The htt(NT) segment has been
      shown to play a critical role in facilitating nucleation of amyloid formation in
      htt N-terminal exon1 fragments. We show here how these Ser-to-Asp mutations
      dramatically affect aggregation kinetics and aggregate structural integrity.
      First, these negatively charged Ser replacements impair the assembly of the alpha
      helical oligomers that play a critical role in htt amyloid nucleation, thus
      providing an explanation for reduced amyloid formation rates. Second, these
      sequence modifications alter aggregate morphology, decrease aggregate stability,
      and enhance the steric accessibility of the htt(NT) segment within the
      aggregates. Together, these changes make the sequence-modified peptides
      kinetically and thermodynamically less likely to aggregate and more susceptible,
      if they do, to posttranslational modifications and degradation. These effects
      also show how phosphorylation of a protein might achieve cellular effects via
      direct impacts on the protein's aggregation properties. In fact, preliminary
      studies on exon1-like molecules containing phosphoryl-Ser residues at positions
      13 and 16 show that they reduce aggregation rates and generate atypical aggregate
      morphologies similar to the effects of the Ser-to-Asp mutants.

PMID- 22999958
TI  - Structural basis for 5'-end-specific recognition of single-stranded DNA by the
      R3H domain from human SMUbp-2.
AB  - The R3H domain is a conserved sequence motif in nucleic acid binding proteins.
      Previously, we reported the solution structure of the R3H domain and identified a
      putative nucleic acid binding site composed of three conserved basic residues
      [Liepinsh, E., Leonchiks, A., Sharipo, A., Guignard, L. & Otting, G. (2003).
      Solution structure of the R3H domain from human SMUbp-2. J. Mol. Biol.326, 217
      223]. Here, we determine the binding affinities of mononucleotides and
      dinucleotides for the R3H domain from human SMUbp-2 (SMUbp2-R3H) and map their
      binding sites on the protein's surface. Although the binding affinities show up
      to 260-fold selectivity between different nucleotides, their binding sites and
      conformations seem very similar. Further, we report the NMR structure of the
      SMUbp2-R3H in complex with deoxyguanosine 5'-monophosphate (dGMP) mimicking the
      5'-end of single-stranded DNA. Pseudocontact shifts from a paramagnetic
      lanthanide tag attached to residue 731 in the mutant A731C confirmed that binding
      of dGMP brings a loop of the protein into closer proximity. The structure
      provides the first structural insight into single-stranded nucleic acid
      recognition by the R3H domain and shows that the R3H domain specifically binds
      the phosphorylated 5'-end through electrostatic interactions with the two
      conserved arginines and stacking interactions with the highly conserved
      histidine.

PMID- 22999957
TI  - The right angle (RA) motif: a prevalent ribosomal RNA structural pattern found in
      group I introns.
AB  - The right angle (RA) motif, previously identified in the ribosome and used as a
      structural module for nano-construction, is a recurrent structural motif of 13
      nucleotides that establishes a 90 degrees  bend between two adjacent helices.
      Comparative sequence analysis was used to explore the sequence space of the RA
      motif within ribosomal RNAs in order to define its canonical sequence space
      signature. We investigated the sequence constraints associated with the RA
      signature using several artificial self-assembly systems. Thermodynamic and
      topological investigations of sequence variants associated with the RA motif in
      both minimal and expanded structural contexts reveal that the presence of a helix
      at the 3' end of the RA motif increases the thermodynamic stability and rigidity
      of the resulting three-helix junction domain. A search for the RA in naturally
      occurring RNAs as well as its experimental characterization led to the
      identification of the RA in groups IC1 and ID intron ribozymes, where it is
      suggested to play an integral role in stabilizing peripheral structural domains.
      The present study exemplifies the need of empirical analysis of RNA structural
      motifs for facilitating the rational design and structure prediction of RNAs.

PMID- 22999959
TI  - Phospholipase Czeta rescues failed oocyte activation in a prototype of male
      factor infertility.
AB  - OBJECTIVE: To determine the effect of infertility-linked sperm phospholipase
      Czeta (PLCzeta) mutations on their ability to trigger oocyte Ca(2+) oscillations
      and development, and also to evaluate the potential therapeutic utility of wild
      type, recombinant PLCzeta protein for rescuing failed oocyte activation and
      embryo development. DESIGN: Test of a novel therapeutic approach to male factor
      infertility. SETTING: University medical school research laboratory. PATIENT(S):
      Donated unfertilized human oocytes from follicle reduction. INTERVENTION(S):
      Microinjection of oocytes with recombinant human PLCzeta protein or PLCzeta cRNA
      and a Ca(2+)-sensitive fluorescent dye. MAIN OUTCOME MEASURE(S): Measurement of
      the efficacy of mutant and wild-type PLCzeta-mediated enzyme activity, oocyte
      Ca(2+) oscillations, activation, and early embryo development. RESULT(S): In
      contrast to the wild-type protein, mutant forms of human sperm PLCzeta display
      aberrant enzyme activity and a total failure to activate unfertilized oocytes.
      Subsequent microinjection of recombinant human PLCzeta protein reliably triggers
      the characteristic pattern of cytoplasmic Ca(2+) oscillations at fertilization,
      which are required for normal oocyte activation and successful embryo development
      to the blastocyst stage. CONCLUSION(S): Dysfunctional sperm PLCzeta cannot
      trigger oocyte activation and results in male factor infertility, so a potential
      therapeutic approach is oocyte microinjection of active, wild-type PLCzeta
      protein. We have demonstrated that recombinant human PLCzeta can phenotypically
      rescue failed activation in oocytes that express dysfunctional PLCzeta, and that
      this intervention culminates in efficient blastocyst formation.

PMID- 22999960
TI  - Much of the genetic risk of colorectal cancer is likely to be mediated through
      susceptibility to adenomas.
AB  - Several single-nucleotide polymorphisms (SNPs) have been associated with
      colorectal cancer (CRC) susceptibility. Most CRCs arise from adenomas, and SNPs
      therefore might affect predisposition to CRC by increasing adenoma risk. We found
      that 8 of 18 known CRC-associated SNPs (rs10936599, rs6983267, rs10795668,
      rs3802842, rs4444235, rs1957636, rs4939827, and rs961253) were over-represented
      in CRC-free patients with adenomas, compared with controls. Ten other CRC
      associated SNPs (rs6691170, rs6687758, rs16892766, rs7136702, rs11169552,
      rs4779584, rs9929218, rs10411210, rs4813802, and rs4925386) were not associated
      significantly with adenoma risk. Genetic susceptibility to CRC in the general
      population is likely to be mediated in part by predisposition to adenomas.

PMID- 22999961
TI  - Replication of hepatitis C virus genotype 3a in cultured cells.
AB  - Hepatitis C virus (HCV) genotype 3a is widespread worldwide, but no replication
      system exists for its study. We describe a subgenomic replicon system for HCV
      genotype 3a. We determined the consensus sequence of an HCV genome isolated from
      a patient, and constructed a subgenomic replicon using this clone. The replicon
      was transfected into HuH-7 cells and RNA replication was confirmed. We identified
      cell culture-adaptive mutations that increased colony formation multiple-fold. We
      have therefore established a genotype 3a replicon system that can be used to
      study this HCV genotype.

PMID- 22999962
TI  - Spanish implantable cardioverter-defibrillator registry. Eighth official report
      of the Spanish Society of Cardiology Working Group on Implantable Cardioverter
      Defibrillators (2011).
AB  - INTRODUCTION AND OBJECTIVES: To summarize the findings of the Spanish Implantable
      Cardioverter-Defibrillator Registry for 2011 compiled by the Electrophysiology
      and Arrhythmia Section of the Spanish Society of Cardiology. METHODS: Each
      implantation team voluntarily and prospectively recorded data on a data
      collection form, which was then sent to the Spanish Society of Cardiology.
      RESULTS: Overall, 4481 device implantations were notified, representing 83.6% of
      the estimated total number of implantations. The notified implantation rate was
      97 per million population and the estimated total implantation rate was 116.2 per
      million. First implantations accounted for 70.2% of the total notified. Data were
      collected from 167 hospitals (22 more than in 2010). Most implantable
      cardioverter-defibrillator implantations took place in men (82.1%). The mean age
      was 62.4 (14.1) years. Most patients had severe or moderate-to-severe ventricular
      dysfunction and were in New York Heart Association functional class II. The most
      frequent underlying cardiac condition was ischemic heart disease, followed by
      dilated cardiomyopathy. The number of indications for primary prevention
      increased over the previous year and accounted for 70.6% of first implantations.
      Overall, 78.4% of implantable cardioverter-defibrillators were implanted by
      cardiac electrophysiologists. CONCLUSIONS: The 2011 Spanish Implantable
      Cardioverter-Defibrillator Registry includes data on almost 84% of all
      implantations of these devices performed in Spain. This was the first year in
      which the number of implants decreased slightly from the previous year, as also
      occurred in the rest of Europe. The percentage of implants for primary prevention
      continued to increase. Full English text available from:www.revespcardiol.org.

PMID- 22999963
TI  - Barth syndrome in adulthood: a clinical case.

PMID- 22999964
TI  - Postextraction bleeding following a fever: a case report.
AB  - Postoperative hemorrhage is one of the few serious complications that can occur
      as a result of dental procedures. We report a case of an elderly patient with
      postextraction bleeding caused by dengue hemorrhagic fever (DHF). Although a
      major sequel of DHF is bleeding secondary to thrombocytopenia, prolonged
      hemorrhage as a result of extraction of tooth has not been reported. In the
      current scenario of emerging and reemerging infections worldwide, dengue is
      gaining global prominence. This case documents the course and progression of this
      disease from a dental perspective and highlights the as yet unreported capacity
      of causing oral complications after dental treatment.

PMID- 22999965
TI  - Reverse cycle chewing before and after orthodontic-surgical correction in class
      III patients.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of reverse
      sequence chewing cycles in skeletal class III patients before and after
      orthodontic-surgical therapy to evaluate whether the occlusal and skeletal
      correction is followed by a functional improvement. STUDY DESIGN: Twenty skeletal
      class III patients (11 males and 9 females, 22.7 +/- 3.0 years old) were
      recruited for this study. All patients received orthodontic and surgical
      treatment. Chewing cycles were recorded with a kinesiograph before (T0) and after
      (T1) therapy. RESULTS: A significant decrease in the number of reverse chewing
      cycles after surgical correction was exhibited in all recordings, when chewing
      either soft or hard boluses, on both the right and the left side. CONCLUSIONS:
      Evaluation of the prevalence of reverse chewing cycles could be considered an
      indicator of functional adaptation after therapy and a method for the early
      detection of nonresponding patients who may require further consideration using a
      different approach.

PMID- 22999966
TI  - Oromandibular dystonia--functional and clinical characteristics: a report on 21
      cases.
AB  - OBJECTIVES: The objectives of this study were to describe subtypes,
      characteristics, and orofacial function of patients with oromandibular dystonia
      and report results of special dental importance. STUDY DESIGN: Symptoms, signs,
      and function were evaluated by questionnaires, video, and clinical and
      physiological examinations in 21 patients with primary and secondary dystonia (13
      focal, 7 segmental, 1 multifocal). RESULTS: A mixture of 2 or more subtypes of
      jaw movements was most common (43%), and the dystonic electromyographic activity
      was frequent in the anterior digastric (62%) and temporal and lateral pterygoid
      (48%) muscles. The impact from the oromandibular dystonia was marked. The
      prevalence of problems with mastication and swallowing was high, as well as with
      hyposalivation, dental attrition, and other dental problems. CONCLUSIONS:
      Patients with oromandibular dystonia may present to dentists with involuntary jaw
      movements and other severe functional problems. Care must be adapted to the
      neurological disorder and may be complicated by the condition itself.

PMID- 22999967
TI  - [Digital replantation in children].
AB  - Digital amputations in children are usually caused by crush or avulsion injuries
      (door hinge, bicycle chain, etc.). The preponderance of this mechanism of injury
      means a survival rate generally lower than in adults. However, finger amputation
      in children is an absolute indication for replantation because the sensory and
      functional results are significantly higher. Technically, there is little
      difference, apart from the difficulty of the size of the structure and the
      presence of growth plates. Kirschner wires are the most suitable fixation method
      but two subcutaneous needles are ideally used in distal amputations. The dressing
      and postoperative immobilization in a circular plaster above the elbow is kept
      for 1 month. Secondary procedures are rare, later than in adults and give poorer
      results because of the difficulty of understanding the active mobilization
      exercises. The postoperative analgesia is fundamental following replantation to
      avoid the risk of arterial spasm, and after a secondary procedure to allow proper
      rehabilitation.

PMID- 22999968
TI  - Time perception in children: a neurodevelopmental approach.
AB  - In this review, we discuss behavioral studies on time perception in healthy
      children that suggest the existence of a primitive "sense" of time in infants as
      well as research that has revealed the changes in time judgments that occur
      throughout childhood. Moreover, a distinction is made between implicit and
      explicit time judgments in order to take account of the different types of
      temporal judgments that emerge across ages. On the basis of both the
      neurobiological model of the internal clock proposed by Matell and Meck (2000),
      and of results of imaging studies in human adults, we then try to identify which
      of the neural structures underlying this primitive sense of time mature faster
      and which mature more slowly in order to explain the age-related variance in time
      judgments. To this end, we also present the small number of timing studies
      conducted among typically and non-typically developing children that have used
      functional magnetic resonance imaging (fMRI) as well as those that have assessed
      the cognitive capacities of such children on the basis of various
      neuropsychological tests.

PMID- 22999969
TI  - An anatomic safe zone for posterior ankle arthroscopy: a cadaver study.
AB  - Posterior ankle arthroscopy has traditionally been associated with concern for
      injury to the posterior tibial nerve and vessels, and this concern is greatest
      when the patient is positioned supine. Positioning the patient prone could be a
      safer method for posterior ankle arthroscopy. The purpose of this cadaver study
      was to determine the anatomic safe zone devoid of vital structures relative to
      the posteromedial and posterolateral arthroscopic portals created. In addition,
      exposure of the posterior ankle was evaluated by direct visualization and
      fluoroscopy to determine the relative utility of these portals. Based on our
      findings, which are consistent with other previously reported results, we believe
      that a wide range of ankle pathology can be suited to treatment by means of
      posterior arthroscopy with the patient in the prone position.

PMID- 22999970
TI  - Is technique performance a prognostic factor in bone marrow stimulation of the
      talus?
AB  - Although results of bone marrow stimulation in osteochondral defects of the talus
      (OCLT) have been satisfactory, the technique performance has not yet been
      subjected to review as a prognostic factor. The aim of this systematic review is
      to determine whether variation within technique influences outcome of bone marrow
      stimulation for OCLT. Electronic databases were searched for articles on OCLT
      treated with bone marrow stimulation techniques, providing a technique
      description. Six articles on microfracture were included (198 patients). Lesion
      size averaged 0.9 cm (2) to 4.5 cm (2), and follow-up varied from 2 to 6 years.
      Key elements were removal of unstable cartilage, hole depth variation between 2
      and 4 mm until bleeding or fat droplets occurred, and a distance between the
      created holes of 3 to 4 mm. The success rate (excellent/good results by any
      clinical outcome score) was 81%. There is a vast similarity in the technique with
      similar outcomes as in previous general reviews; therefore variation in technique
      as currently described in the literature does not seem to influence the outcome
      of bone marrow stimulation for OCLT. Whether the instruments used or the hole
      depth and geometry influence clinical outcome remains to be determined.
      Microfracture is safe and effective for OCLTs smaller than 15 mm. However, in
      this review, only 81% of patients obtained satisfactory results. Larger clinical
      trials are needed with clearly defined patient groups, technique descriptions,
      and reproducible outcome measures to provide insight in the specific indications
      and the preferred technique of bone marrow stimulation.

PMID- 22999971
TI  - Periaqueductal gray neuroplasticity following chronic morphine varies with age:
      role of oxidative stress.
AB  - The development of tolerance to the antinociceptive effects of morphine has been
      associated with networks within ventrolateral periaqueductal gray (vlPAG) and
      separately, nitric oxide signaling. Furthermore, it is known that the mechanisms
      that underlie tolerance differ with age. In this study, we used a rat model of
      antinociceptive tolerance to morphine at two ages, postnatal day (PD) 7 and
      adult, to determine if changes in the vlPAG related to nitric oxide signaling
      produced by chronic morphine exposure were age-dependent. Three pharmacological
      groups were analyzed: control, acute morphine, and chronic morphine group. Either
      morphine (10mg/kg) or equal volume of normal saline was given subcutaneously
      twice daily for 61/2 days. Animals were analyzed for morphine dose-response using
      Hot Plate test. The expression of several genes associated with nitric oxide
      metabolism was evaluated using rtPCR. In addition, the effect of morphine
      exposure on immunohistochemistry for Fos, and nNOS as well as nicotinamide
      adenine dinucleotide phosphate diaphorase (NADPH-d) reaction at the vlPAG were
      measured. In both age groups acute morphine activated Fos in the vlPAG, and this
      effect was attenuated by chronic morphine, specifically in the vlPAG at the level
      of the laterodorsal tegmental nucleus (LDTg). In adults, but not PD7 rats,
      chronic morphine administration was associated with activation of nitric oxide
      function. In contrast, changes in the gene expression of PD7 rats suggested
      superoxide and peroxide metabolisms may be engaged. These data indicate that
      there is supraspinal neuroplasticity following morphine administration as early
      as PD7. Furthermore, oxidative stress pathways associated with chronic morphine
      exposure appear age-specific.

PMID- 22999973
TI  - Participation of antioxidant and cholinergic system in protective effect of
      naringenin against type-2 diabetes-induced memory dysfunction in rats.
AB  - Naringenin is a flavone flavonoid possessing antidiabetic, antioxidant and memory
      improving effects. Therefore, we studied the influence of naringenin against type
      2 diabetes-induced memory dysfunction in rats. Type-2 diabetes was induced by
      high-fat diet and high-fat emulsion for two weeks and a low dose of
      streptozotocin (35 mg/kg). The memory deficit was assessed by using a novel
      object recognition paradigm. The changes in oxidative markers and cholinesterase
      (ChE) levels were evaluated in the hippocampal region. After confirmation of
      diabetes, naringenin (50mg/kg) treatment was given to animals as a preventive and
      in another set of experiments naringenin (25 and 50mg/kg) or pioglitazone
      (5mg/kg) or donepezil (3mg/kg) treatments were started after long-standing
      diabetes (4 weeks after confirmation). Both the treatment schedules show
      significant protection and improvement in cognitive behavior against diabetes
      induced memory dysfunction and biochemical changes. Also, treatment with
      pioglitazone and donepezil improved memory performance in rats. Naringenin was
      found to decrease oxidative stress by depleting elevated lipid peroxide and
      nitric oxide and elevating reduced glutathione levels. Cholinergic function was
      improved by naringenin through the inhibition of elevated ChE activity. In
      conclusion, the present study suggests that naringenin acts as an antioxidant and
      ChE inhibitor against type-2 diabetes-induced memory dysfunction.

PMID- 22999972
TI  - Loss of the Reelin-signaling pathway differentially disrupts heat, mechanical and
      chemical nociceptive processing.
AB  - The Reelin-signaling pathway regulates neuronal positioning during embryonic
      development. Reelin, the extracellular matrix protein missing in reeler mutants,
      is secreted by neurons in laminae I, II and V, binds to Vldl and Apoer2 receptors
      on nearby neurons, and tyrosine phosphorylates the adaptor protein Disabled-1
      (Dab1), which activates downstream signaling. We previously reported that reeler
      and dab1 mutants had significantly reduced mechanical and increased heat
      nociception. Here we extend our analysis to chemical, visceral, and cold pain and
      importantly, used Fos expression to relate positioning errors in mutant mouse
      dorsal horn to changes in neuronal activity. We found that noxious mechanical
      stimulation-induced Fos expression is reduced in reeler and dab1 laminae I-II,
      compared to wild-type mice. Additionally, mutants had fewer Fos-immunoreactive
      neurons in the lateral-reticulated area of the deep dorsal horn than wild-type
      mice, a finding that correlates with a 50% reduction and subsequent
      mispositioning of the large Dab1-positive cells in the mutant lateral-reticulated
      area. Furthermore, several of these Dab1 cells expressed Fos in wild-type mice
      but rarely in reeler mutants. By contrast, paralleling the behavioral
      observations, noxious heat stimulation evoked significantly greater Fos
      expression in laminae I-II of reeler and dab1 mutants. We then used the formalin
      test to show that chemical nociception is reduced in reeler and dab1 mutants and
      that there is a corresponding decrease in formalin-induced Fos expression.
      Finally, neither visceral pain nor cold-pain sensitivity differed between wild
      type and mutant mice. As differences in the nociceptor distribution within reeler
      and dab1 mutant dorsal horn were not detected, these differential effects
      observed on distinct pain modalities suggest that dorsal horn circuits are
      organized along modality-specific lines.

PMID- 22999974
TI  - Bioaccumulation and biomarker responses of cubic and octahedral Cu2O
      micro/nanocrystals in Daphnia magna.
AB  - Great progress has been made in the controlled fabrication of nanomaterials with
      given sizes, shapes, and geometries. However, how such changes in structure
      potentially affect the bioavailability and toxicity of metal nanoparticles to
      aquatic organisms remains mostly unknown. The present study reports the different
      behaviors of two types of Cu(2)O micro/nanocrystals (micro/nano-Cu(2)O) with
      different shapes (cubic and octahedral) and crystallographies (with exposed
      surfaces as {100} or {111}). The bioaccumulation, median lethal concentration,
      and biomarker responses of Daphnia magna exposed to the two micro/nanocrystals
      are also investigated. The Cu accumulation, production of metallothionein (MT),
      and inhibition ratio of D. magna increased gradually with increasing micro/nano
      Cu(2)O concentration. The two crystals showed slight Cu accumulation differences
      toward D. magna, and their biomarker responses and toxicities to D. magna
      differed significantly as well. The octahedral Cu(2)O micro/nanocrystals were
      more toxic to D. magna compared with the cubic micro/nanocrystals probably
      because of the higher surface activities of the {111} facets compared with those
      of the {100} facets for cuprites. Food ingestion was the main entry pathway of
      the micro/nanocrystals into organisms, and toxicity was consequently determined
      based on the dissolution behavior of the micro/nanocrystals in vivo.

PMID- 22999975
TI  - Microbrachytherapy using holmium-166 acetylacetonate microspheres: a pilot study
      in a spontaneous cancer animal model.
AB  - PURPOSE: Holmium-166 acetylacetonate microspheres ((166)Ho-AcAc-MS) are proposed
      as an intratumoral radioablation device. This article presents a pilot study in
      housecats with unresectable liver cancer. Feasibility and tolerability of
      intratumoral administrations of (166)Ho-AcAc-MS was investigated. METHODS AND
      MATERIALS: Three cats with unresectable liver tumors of different histotype were
      included. One cat had hepatocellular carcinoma (HCC), one had cholangiocarcinoma
      (CC), and one had a malignant epithelial liver tumor (MELT) of unspecified
      histotype. (166)Ho-AcAc-MS were injected percutaneously under ultrasound guidance
      into the tumors. Followup consisted of physical examinations and hematologic and
      biochemical analyses. RESULTS: (166)Ho-AcAc-MS were administered to three liver
      tumor-bearing cats. The treatment was well tolerated and the clinical condition,
      that is body weight, alertness, mobility, and coat condition of the animals
      improved markedly. Most biochemical and hematologic parameters normalized shortly
      after treatment. Life of all cats was extended and associated with a good quality
      of life. The HCC cat that received 33-Gy tumor-absorbed dose was euthanized 6
      months after the first administration owing to disease progression. The MELT cat
      received 99-Gy tumor dose and was euthanized 3 months posttreatment owing to
      bacterial meningitis. The CC cat received 333Gy and succumbed 4 months after the
      first treatment owing to the formation of a pulmonary embolism. CONCLUSIONS:
      Percutaneous intratumoral injection of radioactive (166)Ho-AcAc-MS is feasible in
      liver tumor-bearing cats. The findings of this pilot study indicate that (166)Ho
      AcAc-MS may constitute safe brachytherapeutic microspheres and warrant studies to
      confirm the clinical utility of this novel brachytherapy device.

PMID- 22999976
TI  - Effects of oxytocin on human social approach measured using intimacy
      equilibriums.
AB  - Research in animals and humans suggests a role of oxytocin in social approach to
      strangers. We tested this by introducing undergraduate students to opposite
      gendered strangers, with each member of the pair having taken either oxytocin or
      placebo. One hundred and four undergraduate students were paired up and engaged
      in a face-to-face conversation structured with a series of intimate topics for
      discussion. We found that oxytocin increased conversational intimacy in female
      but not male participants, but that this was matched with compensatory decreases
      in eye-contact (relative to placebo). Argyle and Dean (1965) conceptualise
      intimacy as a function of physical distance, eye-contact, and conversational
      intimacy, such that equilibrium is maintained when increases in one domain are
      matched by compensatory decreases in another domain. Based on this notion, our
      results suggest that oxytocin does not facilitate social approach by increasing
      the intimacy equilibrium between two strangers.

PMID- 22999977
TI  - Interrogating noise in protein sequences from the perspective of protein-protein
      interactions prediction.
AB  - The past decades witnessed extensive efforts to study the relationship among
      proteins. Particularly, sequence-based protein-protein interactions (PPIs)
      prediction is fundamentally important in speeding up the process of mapping
      interactomes of organisms. High-throughput experimental methodologies make many
      model organism's PPIs known, which allows us to apply machine learning methods to
      learn understandable rules from the available PPIs. Under the machine learning
      framework, the composition vectors are usually applied to encode proteins as real
      value vectors. However, the composition vector value might be highly correlated
      to the distribution of amino acids, i.e., amino acids which are frequently
      observed in nature tend to have a large value of composition vectors. Thus
      formulation to estimate the noise induced by the background distribution of amino
      acids may be needed during representations. Here, we introduce two kinds of
      denoising composition vectors, which were successfully used in construction of
      phylogenetic trees, to eliminate the noise. When validating these two denoising
      composition vectors on Escherichia coli (E. coli), Saccharomyces cerevisiae (S.
      cerevisiae) and human PPIs datasets, surprisingly, the predictive performance is
      not improved, and even worse than non-denoised prediction. These results suggest
      that the noise in phylogenetic tree construction may be valuable information in
      PPIs prediction.

PMID- 22999978
TI  - Habitat association in populations on landscapes with continuous-valued
      heterogeneous habitat quality.
AB  - We explore a spatially implicit patch-occupancy model of a population on a
      landscape with continuous-valued heterogeneous habitat quality, primarily
      considering the case where the habitat quality of a site affects the mortality
      rate but not the fecundity of individuals at that site. Two analytical approaches
      to the model are constructed, by summing over the sites in the landscape and by
      integrating over the range of habitat quality. We obtain results relating the
      equilibrium population density and all moments of the probability distribution of
      the habitat quality of occupied sites, and relating the probability distributions
      of total habitat quality and occupied habitat quality. Special cases are
      considered for landscapes where habitat quality has either a uniform or a linear
      probability density function. For these cases, we demonstrate habitat
      association, where the quality of occupied sites is higher than the overall mean
      quality of all sites; the discrepancy between the two is reduced at larger
      population densities. The variance of the quality of occupied sites may be
      greater or less than the overall variance of habitat quality, depending on the
      distribution of habitat quality across the landscape. Increasing the variance of
      habitat quality is also shown to increase the ability of a population to persist
      on a landscape.

PMID- 22999979
TI  - A comparison of Erikson's Epigenetic Principle with epigenetics.

PMID- 22999980
TI  - A Mn(II)-Mn(II) center in human prolidase.
AB  - Human prolidase, the enzyme responsible for the hydrolysis of the Xaa-Pro/Hyp
      peptide bonds, is a key player in the recycling of imino acids during the final
      stage of protein catabolism and extracellular matrix remodeling. Its metal active
      site composition corresponding to the maximal catalytic activity is still
      unknown, although prolidase function is of increasing interest due to the link
      with carcinogenesis and mutations in prolidase gene cause a severe connective
      tissue disorder. Here, using EPR and ICP-MS on human recombinant prolidase
      produced in Escherichia coli (hRecProl), the Mn(II) ion organized in a dinuclear
      Mn(II)-Mn(II) center was identified as the protein cofactor. Furthermore, thermal
      denaturation, CD/fluorescence spectroscopy and limited proteolysis revealed that
      the Mn(II) is required for the proper protein folding and that a protein
      conformational modification is needed in the transition from apo- to Mn(II)loaded
      enzyme. The collected data provided a better knowledge of the human holo
      prolidase and, although limited to the recombinant enzyme, the exact identity and
      organization of the metal cofactor as well as the conformational change required
      for activity were proven.

PMID- 22999982
TI  - Anesthetic management of a parturient with spinal muscular atrophy type II.
AB  - In the past, pregnancy was contraindicated in patients with spinal muscular
      atrophy. Recently, more cases are occurring because of improvement in survival
      and functional status. The goals for anesthetic management of these patients
      include satisfactory anesthesia during surgery and excellent postoperative
      analgesia with minimal compromise of respiratory function. Spinal anesthesia may
      be considered contraindicated due to spinal deformities, but successful spinal
      anesthesia was performed in a 37 year old parturient following magnetic resonance
      imaging of the spine.

PMID- 22999981
TI  - Structure-activity relationship for enantiomers of potent inhibitors of B.
      anthracis dihydrofolate reductase.
AB  - BACKGROUND: Bacterial resistance to antibiotic therapies is increasing and new
      treatment options are badly needed. There is an overlap between these resistant
      bacteria and organisms classified as likely bioterror weapons. For example,
      Bacillus anthracis is innately resistant to the anti-folate trimethoprim due to
      sequence changes found in the dihydrofolate reductase enzyme. Development of new
      inhibitors provides an opportunity to enhance the current arsenal of anti-folate
      antibiotics while also expanding the coverage of the anti-folate class. METHODS:
      We have characterized inhibitors of B. anthracis dihydrofolate reductase by
      measuring the K(i) and MIC values and calculating the energetics of binding. This
      series contains a core diaminopyrimidine ring, a central dimethoxybenzyl ring,
      and a dihydrophthalazine moiety. We have altered the chemical groups extended
      from a chiral center on the dihydropyridazine ring of the phthalazine moiety. The
      interactions for the most potent compounds were visualized by X-ray structure
      determination. RESULTS: We find that the potency of individual enantiomers is
      divergent with clear preference for the S-enantiomer, while maintaining a high
      conservation of contacts within the binding site. The preference for enantiomers
      seems to be predicated largely by differential interactions with protein residues
      Leu29, Gln30 and Arg53. CONCLUSIONS: These studies have clarified the activity of
      modifications and of individual enantiomers, and highlighted the role of the less
      active R-enantiomer in effectively diluting the more active S-enantiomer in
      racemic solutions. This directly contributes to the development of new
      antimicrobials, combating trimethoprim resistance, and treatment options for
      potential bioterrorism agents.

PMID- 22999983
TI  - Comparative utility of centrally versus peripherally transduced venous pressure
      monitoring in the perioperative period in spine surgery patients.
AB  - STUDY OBJECTIVE: To compare central venous pressure (CVP) with peripheral venous
      pressure (PVP) monitoring during the intraoperative and postoperative periods in
      patients undergoing spine surgery. DESIGN: Prospective observational study.
      SETTING: University-affiliated teaching hospital. PATIENTS: 35 ASA physical
      status 1, 2, and 3 patients. INTERVENTIONS: A peripheral catheter in the forearm
      or hand and a central catheter into the internal jugular vein were placed for PVP
      and CVP monitoring, respectively. MEASUREMENTS: CVP and PVP values were collected
      simultaneously and recorded electronically at 5-minute intervals throughout
      surgery and in the recovery room. The number of attempts for catheter placement,
      ease of use, maintenance, and interpretation were recorded. Patient comfort,
      frequency of complications, and cost were analyzed. MAIN RESULTS: The correlation
      coefficient between CVP and PVP was 0.650 in the operating room (P < 0.0001) and
      0.388 in the recovery room (P < 0.0001). There was no difference between groups
      in number of attempts to place either catheter, maintenance, and interpretation
      with respect to PVP and CVP monitoring in the operating room. In the recovery
      room, the nurses reported a higher level of difficulty in interpretation of PVP
      than CVP, but no differences were noted in ease of maintenance. There were no
      complications related to either central or peripheral catheter placement. Patient
      comfort and cost efficiency were higher with a peripheral than a central
      catheter. CONCLUSION: During clinically relevant conditions, there was limited
      correlation between PVP and CVP in the prone position during surgery and
      postoperatively in the recovery room.

PMID- 22999984
TI  - A randomized controlled trial comparing Laryngeal Mask Airway removal during
      adequate anesthesia and after awakening in children aged 2 to 6 years.
AB  - STUDY OBJECTIVE: To compare the frequency of airway complications during removal
      of the Laryngeal Mask Airway (LMA) in 2 to 6 year old pediatric patients. DESIGN:
      Prospective randomized study. SETTING: Operating room at a university hospital.
      PATIENTS: 92 ASA physical status 1 and 2 pediatric patients, aged 2 to 6 years.
      INTERVENTIONS: Participants were randomized to two groups: anesthesia state
      (anesthesia group) and awake state (awake group). Anesthesia was induced and
      maintained with sevoflurane. Patients were allowed to maintain spontaneous
      respiration. In the anesthesia group, the LMA was removed during anesthesia with
      2.2% of sevoflurane. In the awake group, the LMA was removed when patients met
      the recovery criteria, including facial grimace, spontaneous eye opening, and
      purposeful arm movement. MEASUREMENTS: During and after removal of the LMA, the
      frequencies of airway-related complications including cough, severe salivation,
      LMA biting or teeth clenching, breath holding, laryngospasm, desaturation (SpO(2)
      < 95%), and vomiting, were recorded. The frequencies of upper airway obstruction
      and duration of emergence from anesthesia also were compared. MAIN RESULTS: The
      frequency of airway-related complications was significantly less in the
      anesthesia group than the awake group (4.8% vs 37.2%, P = 0.001). Of the
      complications, cough, desaturation, excessive secretion, and LMA biting were less
      common in the anesthesia group. No differences between groups were noted in the
      frequency of upper airway obstruction and duration of emergence from anesthesia.
      CONCLUSION: In 2 to 6 year old pediatric patients, an adequate anesthetic state
      is preferable to the awake state during LMA removal, producing fewer
      complications.

PMID- 22999985
TI  - Diagnosis of broken-bars fault in induction machines using higher order spectral
      analysis.
AB  - Detection and identification of induction machine faults through the stator
      current signal using higher order spectra analysis is presented. This technique
      is known as motor current signature analysis (MCSA). This paper proposes two
      higher order spectra techniques, namely the power spectrum and the slices of bi
      spectrum used for the analysis of induction machine stator current leading to the
      detection of electrical failures within the rotor cage. The method has been
      tested by using both healthy and broken rotor bars cases for an 18.5 kW-220 V/380
      V-50 Hz-2 pair of poles induction motor under different load conditions.
      Experimental signals have been analyzed highlighting that bi-spectrum results
      show their superiority in the accurate detection of rotor broken bars. Even when
      the induction machine is rotating at a low level of shaft load (no-load
      condition), the rotor fault detection is efficient. We will also demonstrate
      through the analysis and experimental verification, that our proposed proposed
      method has better detection performance in terms of receiver operation
      characteristics (ROC) curves and precision-recall graph.

PMID- 22999986
TI  - Fibroadenoma: can fine needle aspiration biopsy avoid short term follow-up?
AB  - OBJECTIVE: To confirm whether fine needle aspiration biopsy (FNAB) can avoid
      close monitoring, a source of worry for women patients with a suspected
      fibroadenoma found by ultrasound, and requiring their compliance. PATIENTS AND
      METHODS: Over 39months, 427 nodules with a diagnosis of fibroadenoma were sampled
      in 372 patients using ultrasound-guided FNAB. The sonographic appearance of all
      the nodules suggested BI-RADS category 3 fibroadenomas. The mean size of the
      fibroadenomas was 9mm. The mean duration of follow-up was 29.7months. RESULTS:
      Seven nodules had atypical cytology: a microbiopsy and/or excision found a simple
      fibroadenoma (n=3), mastitis (n=1), a fibroadenoma associated with a papilloma
      (n=1), fibrosis (n=1) and normal tissue (n=1). Seven other nodules were resected
      during treatment for synchronous cancer, and were diagnosed as fibroadenomas. Two
      hundred and seventy-six nodules were followed-up (121 patients were lost to
      follow-up [n=132]) and the appearance of 263 nodules (95.29%) was stable. Seven
      nodules, which had increased in size, underwent another FNAB or microbiopsy or
      surgery. Five nodules were not found again. The borders of one nodule showed
      modifications. CONCLUSION: The use of fine needle aspiration biopsy, interpreted
      by an experienced cytologist, means that short term follow-up of fibroadenomas
      can be avoided.

PMID- 22999987
TI  - An outcome of evidence-based practice education: sustained clinical decision
      making among bedside nurses.
AB  - This research described factors related to incorporating evidence-based practice
      for clinical decision-making by staff nurses who completed an evidence-based
      practice (EBP) scholars program. A phenomenological approach was used with focus
      groups to collect data. A semi-structured questionnaire and field notes comprised
      study instruments. Audio tapes were transcribed and semantic content analysis was
      used to code data. Programs to teach bedside nurses how to incorporate EBP into
      care delivery not only result in better outcomes for patients but also greatly
      contribute to the sustained enculturation of EBP as a foundation for nursing
      practice. 

PMID- 22999988
TI  - Neurobehavioral assessment of infants born at term and in utero exposure to
      serotonin reuptake inhibitors.
AB  - BACKGROUND: Some studies report neurobehavioral symptoms in neonates exposed to
      serotonin reuptake inhibitors (SRIs) in utero. However, maternal psychiatric
      illness during the last trimester of pregnancy, as a confounding factor, has not
      always been assessed. AIMS: In this prospective study we compared neurobehavioral
      complications among neonates who were born to euthymic women who either took or
      did not take an SRI during the last trimester of pregnancy. STUDY DESIGN: Exposed
      and unexposed infants were assessed for: 1) temperament as measured by the
      Neonatal Behavioral Assessment Scale (NBAS); 2) activity via Actiwatch electronic
      monitoring; 3) sleep state using trained observer ratings; and 4) perinatal
      complications through medical record review. T-tests, Fisher's exact tests, and
      analyses of covariance were used to assess the relationship between clinical and
      neurobehavioral factors and exposure status. SUBJECTS: 67 infants (61 controls
      and 6 exposed to SRIs). OUTCOME MEASURES: Neonatal Assessment Behavioral Scale,
      APGAR scores, infant sleep state (% sleep, % wakeful), startles and
      tremulousness, gestational age, birth weight, and head circumference. RESULTS:
      Infants exposed to SRIs in the third trimester had poorer motor development,
      lower 5-minute APGAR scores, and shorter mean gestational age as compared to
      unexposed infants. CONCLUSION: Results of this study show differences in
      autonomic and gross motor activity between neonates who were or were not exposed
      to SRIs in utero after controlling for active maternal psychiatric illness.
      Future longitudinal work should compare longer term outcomes of exposed and
      unexposed infants of depressed mothers.

PMID- 22999989
TI  - New flavones with antidiabetic activity from Callistemon lanceolatus DC.
AB  - Phytochemical investigation of the aerial parts of Callistemon lanceolatus DC
      (Myrtaceae) led to the isolation of two new flavones characterized as 5,7
      dihydroxy-6,8-dimethyl- 4' -methoxy flavone (1) and 8-(2-hydroxypropan-2-yl)-5
      hydroxy-7-methoxy-6-methyl-4'-methoxy flavone (2) along with the seven known
      phytoconstituents. The structures of new compounds have been established on the
      basis of chemical and spectral studies and known compounds were compared with the
      published literature data. The isolated flavones exhibited blood glucose lowering
      effect in streptozotocin induced diabetic rats.

PMID- 22999990
TI  - Pharmacokinetic study of luteolin, apigenin, chrysoeriol and diosmetin after oral
      administration of Flos Chrysanthemi extract in rats.
AB  - Flos Chrysanthemi (the flower of Chrysanthemum morifolium Ramat.) is widely used
      in China as a food and traditional Chinese medicine for many diseases. Luteolin
      and apigenin are two main bioactive components in Flos Chrysanthemi, and
      chrysoeriol and diosmetin are two methylated metabolites of luteolin in vivo by
      cathechol-O-methyltransferase (COMT). However, there was lack of pharmacokinetic
      information of chrysoeriol and diosmetin after oral administration of Flos
      Chrysanthemi extract (FCE). The present study aimed to develop an HPLC-UV method
      for simultaneous determination of rat plasma concentration of luteolin, apigenin,
      chrysoeriol and diosmetin and utilize it in pharmacokinetic study of the four
      compounds after orally giving FCE to rats. The method was successfully validated
      and applied to the pharmacokinetic study when oral administration of FCE to rats
      with or without co-giving a COMT inhibitor, entacapone. Chrysoeriol and diosmetin
      were detected in rat plasma after oral administration of FCE and their
      concentrations were significantly decreased after co-giving entacapone.
      Furthermore, AUC of luteolin was significantly increased by entacapone, while
      that of chrysoeriol was decreased by entacapone, which revealed COMT might play
      an important role in the disposition of luteolin in rats after dosing of FCE. In
      conclusion, a sensitive, accurate and reproducible HPLC-UV method for
      simultaneous determination of luteolin, apigenin, chrysoeriol and diosmetin in
      rat plasma were developed, pharmacokinetics of chrysoeriol and diosmetin combined
      with luteolin and apigenin were characterized after oral administration of FCE to
      rats, which gave us more information on pharmacokinetics and potential
      pharmacological effects of FCE in vivo.

PMID- 22999991
TI  - One-pot three-component synthesis of novel heterocyclic steroids as a central
      antioxidant and anti-inflammatory agents.
AB  - Oxidative stress and inflammation have been implicated in several
      neurodegenerative and developmental brain disorders. The present work was devoted
      to the design and synthesis of novel steroid derivatives bearing promising
      heterocyclic moiety that would act to reduce neuro-inflammation and oxidative
      stress in brain. The novel heterocyclic steroids were synthesized and their
      chemical structures were confirmed by studying their analytical and spectral
      data. The tested compounds were assayed in the model of neuro-inflammation
      produced in rats by cerebral lipopolysaccharide injection. The intracerebral
      administration of bacterial endotoxin resulted in cerebral inflammatory state
      evidenced by increased malondialdehyde (MDA), decreased reduced glutathione (GSH)
      level, increased nitric oxide as well as increased acetylcholinesterase (AChE)
      activity in the brain. Compounds 6, 10, 8b and 13a markedly increased reduced
      glutathione. Malondialadehyde and nitric oxide levels were reduced to normal
      values after treatment with all tested compounds. AChE activity was normalized by
      compound 8b and reduced to below normal values by compounds 10 and 14a. These
      results are exciting in that these agents might be useful candidates in treatment
      of cerebral inflammation.

PMID- 22999992
TI  - An improved synthesis of 6alpha-ethylchenodeoxycholic acid (6ECDCA), a potent and
      selective agonist for the Farnesoid X Receptor (FXR).
AB  - The active, potent, and selective Farnesoid X Receptor (FXR) agonist 6alpha
      ethylchenodeoxycholic acid (6ECDCA) has been synthesized in improved yield
      compared to the published methodologies. The synthesis employed selective
      oxidation of one of the two hydroxyls of the readily-available starting material
      chenodeoxycholic acid (CDCA) as a key step. After protection of the remaining
      hydroxyl, LDA/HMPA/EtI/PPTS provided an efficient
      deprotonation/ethylation/deprotection sequence. The two synthetic improvements
      that allow a productive yield are the use of PCC in the oxidation step, and the
      use of HMPA/ethyl iodide in the stereoselective alkylation step. This synthesis
      offers an economical and efficient strategy which provides a simple and cost
      effective procedure for potential large-scale production of this promising FXR
      agonist, which is a research tool and potential drug substance of current
      interest.

PMID- 22999993
TI  - Association between dietary behaviors and attention-deficit/hyperactivity
      disorder and learning disabilities in school-aged children.
AB  - We aimed to comprehensively investigate the associations between a wide range of
      measures of dietary behaviors and learning disabilities and attention
      deficit/hyperactivity disorder (ADHD) in community-dwelling Korean children in
      order to generate hypotheses for future work. The present study included 986
      children [507 boys, 479 girls; mean (S.D.) age=9.1 (0.7) years] recruited from
      five South Korean cities. Children's dietary behaviors were assessed by the mini
      dietary assessment (MDA) for Koreans. It consists of ten items to assess the
      level of intake of dairy products, high-protein foods, vegetables, fried foods,
      fatty meats, salt, and sweetened desserts and whether the subject is eating three
      regular meals and has a balanced diet. Learning disability was assessed via the
      Learning Disability Evaluation Scale (LDES). ADHD was assessed via the Diagnostic
      Interview Schedule for Children version-IV and the ADHD rating scale, and ADHD
      related behavioral problems were assessed via the Child Behavior Checklist. After
      adjusting for potential confounders, a high intake of sweetened desserts, fried
      food, and salt is associated with more learning, attention, and behavioral
      problems, whereas a balanced diet, regular meals, and a high intake of dairy
      products and vegetables is associated with less learning, attention, and
      behavioral problems. Our data suggest that existing encouraged dietary habits
      mostly have beneficial effects on learning, attention, and behavioral problems in
      Korean children. These findings are in general the same results in other studies
      on ADHD children in other countries. However, the cross-sectional study design
      prevents our ability to assess causal relationships.

PMID- 22999994
TI  - Recruitment and retention strategies in a clinical trial for children with
      chronic hepatitis C infection.
AB  - Successful strategies for recruitment and retention (R & R) in pediatric trials
      are needed. The purpose of our study was to analyze the effectiveness of R&R in a
      trial for children with hepatitis C. Recruitment strategies were (1) Initial
      (months 0-12) and (2) extra effort (months 13-18). Initial strategies enrolled
      70/114 (61%) of patients. Extra effort strategies included: (1) radio broadcasts,
      (2) contact with adult hepatologists, (3) dissemination of study material and (4)
      modification of the exclusion criteria. The overall retention rate was 84% at 2
      years. Lessons learned will be valuable in designing future pediatric trials.

PMID- 22999995
TI  - Histone methylation defines an epigenetic entity in penile squamous cell
      carcinoma.
AB  - PURPOSE: Earlier studies indicate that epigenetics contribute to the pathogenesis
      of penile squamous cell carcinoma. Histone methylation patterns are frequently
      altered during carcinogenesis. Therefore, we investigated the methylation pattern
      of the histones H3K4, H3K9 and H3K27 in penile carcinoma and normal tissue.
      MATERIALS AND METHODS: A tissue microarray was constructed with 65 penile
      carcinomas, 6 metastatic lesions and 30 control tissues. Global histone
      methylation was assessed using immunohistochemistry. RESULTS: Global levels of
      H3K4me1, H3K9me1, H3K9me2, H3K27me2 and H3K27me3 were decreased, whereas H3K9me3
      was increased in penile carcinoma. Histone methylation levels defined an
      epigenetic entity that allowed accurate differentiation of cancer and normal
      samples. We observed no correlation of histone methylation levels with
      clinicopathological parameters or patient outcome. CONCLUSIONS: The description
      of a definite epigenetic entity in penile carcinoma provides a rationale for
      testing epigenetic agents in patients with metastatic disease.

PMID- 22999996
TI  - JTS-653 blocks afferent nerve firing and attenuates bladder overactivity without
      affecting normal voiding function.
AB  - PURPOSE: We evaluated the role of TRPV1 in bladder overactivity based on afferent
      nerve firing and urodynamic parameters using the selective TRPV1 antagonist JTS
      653. MATERIALS AND METHODS: We evaluated the effects of JTS-653 on the increased
      pelvic nerve discharge and intravesical pressure induced by intravesical infusion
      of 100 MUM capsaicin in anesthetized rats. The effects of JTS-653 on the
      urodynamic parameters of bladder overactivity induced by intravesical infusion of
      30 nM resiniferatoxin or 0.2% acetic acid, or on normal bladder activity were
      evaluated by cystometry in conscious rats. The effects of JTS-653 on carbachol
      induced contraction were investigated using bladder muscle strips. RESULTS: JTS
      653 significantly suppressed the capsaicin induced increase in nerve discharge
      and intravesical pressure. Intravesical infusion of resiniferatoxin or acetic
      acid decreased the intercontraction interval and voided volume. JTS-653
      significantly increased the intercontraction interval and voided volume in rats
      with resiniferatoxin or acetic acid induced bladder overactivity without
      affecting maximal voiding pressure. The antimuscarinic agent propiverine
      significantly decreased maximal voiding pressure but did not affect the
      intercontraction interval or voided volume in rats with acetic acid induced
      bladder overactivity. In normal rats JTS-653 showed no significant effects on the
      intercontraction interval, voided volume or maximal voiding pressure. JTS-653 did
      not affect carbachol induced contraction of the bladder muscle. CONCLUSIONS: Our
      findings suggest that TRPV1 is involved in bladder overactivity via afferent
      nerve activation but it is not associated with normal voiding function. A TRPV1
      antagonist would be a useful drug for bladder overactivity with a different
      pharmacological profile than antimuscarinic agents.

PMID- 22999997
TI  - Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.
AB  - PURPOSE: Diabetes mellitus causes diabetic bladder dysfunction. We identified the
      pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in
      rats. MATERIALS AND METHODS: A total of 72 female Sprague-Dawley(r) rats were
      divided into 6 groups, including age matched controls, and rats with sham urinary
      diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham
      urinary diversion, streptozotocin induced diabetes mellitus after urinary
      diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary
      diversion was performed by ureterovaginostomy 10 days before diabetes mellitus
      induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis
      induction. We measured 24-hour drinking and voiding volumes, and cystometry.
      Bladders were harvested to quantify smooth muscle, urothelium and collagen. We
      measured nitrotyrosine and Mn superoxide dismutase in the bladder. RESULTS:
      Diabetes and diuresis caused increases in drinking and voiding volume, and
      bladder weight. Bladder weight decreased in the urinary diversion group and the
      urinary diversion plus diabetes group. The intercontractile interval, voided
      volume and compliance increased in the diuresis and diabetes groups, decreased in
      the urinary diversion group and further decreased in the urinary diversion plus
      diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas
      increased in the diuresis and diabetes groups, and decreased in the urinary
      diversion and urinary diversion plus diabetes groups. As a percent of total
      tissue area, collagen decreased in the diuresis and diabetes groups, and
      increased in the urinary diversion and urinary diversion plus diabetes groups.
      Smooth muscle and urothelium decreased in the urinary diversion and urinary
      diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase
      increased in rats with diabetes and urinary diversion plus diabetes. CONCLUSIONS:
      Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial
      oxidative stress in the bladder, which may have a pathogenic role in late stage
      diabetic bladder dysfunction.

PMID- 22999998
TI  - Clinical utility of an epigenetic assay to detect occult prostate cancer in
      histopathologically negative biopsies: results of the MATLOC study.
AB  - PURPOSE: Concern about possible false-negative prostate biopsy histopathology
      findings often leads to rebiopsy. A quantitative methylation specific polymerase
      chain reaction assay panel, including GSTP1, APC and RASSF1, could increase the
      sensitivity of detecting cancer over that of pathological review alone, leading
      to a high negative predictive value and a decrease in unnecessary repeat
      biopsies. MATERIALS AND METHODS: The MATLOC study blindly tested archived
      prostate biopsy needle core tissue samples of 498 subjects from the United
      Kingdom and Belgium with histopathologically negative prostate biopsies, followed
      by positive (cases) or negative (controls) repeat biopsy within 30 months.
      Clinical performance of the epigenetic marker panel, emphasizing negative
      predictive value, was assessed and cross-validated. Multivariate logistic
      regression was used to evaluate all risk factors. RESULTS: The epigenetic assay
      performed on the first negative biopsies of this retrospective review cohort
      resulted in a negative predictive value of 90% (95% CI 87-93). In a multivariate
      model correcting for patient age, prostate specific antigen, digital rectal
      examination and first biopsy histopathological characteristics the epigenetic
      assay was a significant independent predictor of patient outcome (OR 3.17, 95% CI
      1.81-5.53). CONCLUSIONS: A multiplex quantitative methylation specific polymerase
      chain reaction assay determining the methylation status of GSTP1, APC and RASSF1
      was strongly associated with repeat biopsy outcome up to 30 months after initial
      negative biopsy in men with suspicion of prostate cancer. Adding this epigenetic
      assay could improve the prostate cancer diagnostic process and decrease
      unnecessary repeat biopsies.

PMID- 22999999
TI  - A synthetic polyvalent ligand for alpha5beta1 integrin activates components of
      the urothelial carcinoma cell response to bacillus Calmette-Guerin.
AB  - PURPOSE: Prior study has shown that bacillus Calmette-Guerin binds to and cross
      links alpha5beta1 integrins present on the surface of urothelial carcinoma cells.
      Antibody mediated cross-linking of alpha5beta1 integrins can reproduce signal
      transduction, gene transactivation and phenotypic changes, similar to those
      observed in response to bacillus Calmette-Guerin. We evaluated the effect of a
      synthetic polyvalent ligand for alpha5beta1 on these elements of the tumor
      response to bacillus Calmette-Guerin. MATERIALS AND METHODS: The consensus
      alpha5beta1 integrin binding tripeptide RGD was linked to a MAP8 backbone to
      result in an octavalent construct targeting alpha5beta1 integrin. RGD-MAP8 was
      used to determine its effect on signaling pathway activation (nuclear factor
      kappaB, NRF2 and CEBP), gene expression (p21, interleukin-6 and 8, CXCL1, CXCL2
      and CCL20) and cytotoxicity (trypan blue exclusion and HMGB1 release) in human
      urothelial carcinoma cells. Results were compared to those of treatment with
      bacillus Calmette-Guerin or the missense peptide GRD-MAP8. RESULTS: The RDG-MAP8
      construct significantly increased nuclear factor-kappaB signaling and p21
      expression relative to controls. Compared to bacillus Calmette-Guerin treatment,
      only p21 expression was comparable for cells treated with RGD-MAP8, averaging 70%
      of bacillus Calmette-Guerin induced expression. RGD-MAP8 failed to have a
      significant effect on CEBP or NRF2 activation, gene expression or cell viability.
      CONCLUSIONS: Intracellular signaling, gene transactivation and phenotypic changes
      in response to RGD-MAP8 were qualitatively and quantitatively different than
      those observed in response to bacillus Calmette-Guerin. Results suggest that
      while alpha5beta1 integrin cross-linking contributes to the bacillus Calmette
      Guerin response, it alone is insufficient to duplicate the full spectrum of
      bacillus Calmette-Guerin induced changes in urothelial carcinoma cell biology.

PMID- 23000000
TI  - Involvement of Rho-kinase signaling pathways in nerve evoked and spontaneous
      contractions of the Guinea pig prostate.
AB  - PURPOSE: Men with benign prostatic hyperplasia commonly experience irritative
      lower urinary tract symptoms, which are due at least in part to enhanced
      prostatic smooth muscle tone. To provide some insight into the changes that occur
      in prostatic contractility with age, we examined the contribution of rho-kinase
      dependent Ca(2+) sensitization in neurogenic and spontaneous contractions of
      young and aging guinea pig prostates. MATERIALS AND METHODS: We used conventional
      tension recording and electrophysiological intracellular microelectrode recording
      techniques. RESULTS: The Rho-kinase inhibitor Y-27632 (10 and 100 MUM)
      significantly inhibited electrical field stimulated evoked (neurogenic)
      contractions in the guinea pig prostate in a dose dependent manner. In addition,
      Y-27632 (1 and 10 MUM) similarly suppressed tetrodotoxin insensitive spontaneous
      contractions in dose dependent fashion. While Y-27632 at 10 MUM decreased
      spontaneous contractions of young and aging guinea pig prostates, as evidenced by
      a significant decrease in the AUC, there was no significant difference in the
      degree of inhibition between the 2 age groups. In contrast to contractile
      activity, Y-27632 did not affect the generation or modulation of spontaneous slow
      wave electrical activity, which underlies spontaneous contractions. CONCLUSIONS:
      There are strong indicators that Rho-kinase signaling pathways have a significant
      role in prostatic smooth muscle contractility, most likely independent of
      cytosolic Ca(2+) levels. Features of the rho-kinase pathway may well represent
      alternative, novel future therapeutic targets to reduce prostatic contractility,
      thereby alleviating the lower urinary tract symptoms arising from benign
      prostatic hyperplasia.

PMID- 23000002
TI  - Development of a satisfactory and general continuous assay for aminotransferases
      by coupling with (R)-2-hydroxyglutarate dehydrogenase.
AB  - A continuous general spectrophotometric assay for measuring the activity of
      aminotransferases has been developed. It is based on the transamination of a keto
      compound (amino acceptor) and l-glutamate (amino donor), yielding the
      corresponding amino compound and 2-oxoglutarate. The rate of formation of 2
      oxoglutarate is measured in a coupled reaction with overproduced recombinant
      nicotinamide adenine dinucleotide (NAD(+))-dependent (R)-2-hydroxyglutarate
      dehydrogenase from Acidaminococcus fermentans, with the rate of absorbance
      decrease at 340nm indirectly reflecting the aminotransferase activity. This new
      method allows continuous monitoring of the course of transamination. Because
      glutamate and 2-oxoglutarate are obligatory participants in most biological
      transamination reactions, a coupled assay based on measuring the formation of 2
      oxoglutarate has very wide applicability. The article demonstrates its utility
      with branched-chain amino acid aminotransferase and l-valine:pyruvate
      aminotransferase.

PMID- 23000003
TI  - Quantitative determination of isopentenyl diphosphate in cultured mammalian
      cells.
AB  - Isopentenyl diphosphate (IPP), an intermediate of the isoprenoid biosynthetic
      pathway (IBP), has several important biological functions, yet a method to
      determine its basal level has not been described. Here, we describe a
      nonradioactive and sensitive analytical method to isolate and specifically
      quantify IPP from cultured mammalian cells. This method applies an enzymatic
      coupling reaction to determine intracellular concentrations of IPP. In this
      reaction, geranylgeranyl diphosphate synthase catalyzes the formation of
      geranylgeranyl diphosphate (GGPP) from IPP and farnesyl diphosphate (FPP).
      Subsequently, geranylgeranyl protein transferase I conjugates GGPP with a
      fluorescently labeled peptide. The geranylgeranylated peptide can be quantified
      by high-performance liquid chromatography (HPLC) with a fluorescence detector,
      thereby allowing for IPP quantification. The detection lower limit of the
      fluorescence-labeled geranylgeranyl peptide is approximately 5 pg (~0.017 pmol).
      This method was used to examine the effects of IBP inhibitors such as lovastatin
      and zoledronate on intracellular levels of IPP. Inhibition of
      hydroxymethylglutaryl coenzyme A reductase (HMGCR) by lovastatin (50 nM)
      decreases IPP levels by 78% and 53% in K562 and MCF-7 cells, respectively.
      Whereas zoledronic acid (10 MUM) increased IPP levels 12.6-fold when compared
      with untreated cells in the K562 cell line, an astonishing 960-fold increase was
      observed in the MCF-7 cells.

PMID- 23000004
TI  - Cysteine-terminated B-domain of Staphylococcus aureus protein A as a scaffold for
      targeting GABA(A) receptors.
AB  - This study reports the preparation and characterization of cysteine-terminated B
      domain (Bd-cys) of Staphylococcus aureus protein A, in combination with
      immunoglobulin G (IgG) antibodies directed against the rho1 and alpha1 subunits
      of GABA(A) receptors, for localizing reagents of interest to the target receptor.
      A cysteine residue was inserted at the C terminus of the cysteine-lacking B
      domain (Bd) and used for conjugating maleimide-containing compounds. As
      determined by enzyme-linked immunosorbent assay (ELISA), binding of a Bd-cys-S
      fluorescein conjugate to polyclonal guinea pig anti-GABA(A)-rho1 and rabbit anti
      GABA(A)-alpha1 IgG was similar to that exhibited by full-length protein A.
      Surface plasmon resonance analysis of the interaction of Bd-cys-S-PEG3400-biotin
      conjugate (where PEG is polyethylene glycol) with anti-GABA(A)-rho1 and anti
      GABA(A)-alpha1 yielded K(D) values of 6.4 +/- 1.9 and 0.4 +/- 0.1 nM,
      respectively. Fluorescence anisotropy analysis of the binding of Bd-cys-S
      fluorescein to the two antibodies yielded EC50 values of 65 and 18 nM,
      respectively. As determined with biotin-reactive fluorescent reagents, Bd-cys-S
      PEG3400-biotin specifically bound to the plasma membrane of Xenopus laevis
      oocytes that expressed alpha1beta2gamma2 or homomeric rho1 GABA(A) receptors and
      were pretreated with the corresponding anti-GABA(A) IgG. The IgG-binding
      specificity and high affinity of Bd-cys conjugates illustrate the potential of
      these conjugates, in combination with a selected IgG, to localize compounds of
      interest at specific cell surface proteins.

PMID- 23000005
TI  - Development of pyrethroid-like fluorescent substrates for glutathione S
      transferase.
AB  - The availability of highly sensitive substrates is critical for the development
      of precise and rapid assays for detecting changes in glutathione S-transferase
      (GST) activity that are associated with GST-mediated metabolism of insecticides.
      In this study, six pyrethroid-like compounds were synthesized and characterized
      as substrates for insect and mammalian GSTs. All of the substrates were esters
      composed of the same alcohol moiety, 7-hydroxy-4-methylcoumarin, and acid
      moieties that structurally mimic some commonly used pyrethroid insecticides,
      including cypermethrin and cyhalothrin. CpGSTD1, a recombinant Delta class GST
      from the mosquito Culex pipiens pipiens, metabolized our pyrethroid-like
      substrates with both chemical and geometric preference (i.e., the cis-isomers
      were metabolized at 2- to 5-fold higher rates than the corresponding trans
      isomers). A GST preparation from mouse liver also metabolized most of our
      pyrethroid-like substrates with both chemical and geometric preference but at 10-
      to 170-fold lower rates. CpGSTD1 and mouse GSTs metabolized 1-chloro-2,4
      dinitrobenezene (CDNB), a general GST substrate, at more than 200-fold higher
      rates than our novel pyrethroid-like substrates. There was a 10-fold difference
      in the specificity constant (k(cat)/K(M) ratio) of CpGSTD1 for CDNB and those of
      CpGSTD1 for cis-DCVC and cis-TFMCVC, suggesting that cis-DCVC and cis-TFMCVC may
      be useful for the detection of GST-based metabolism of pyrethroids in mosquitoes.

PMID- 23000006
TI  - A sub-Tenon's capsule injection of lidocaine induces extraocular muscle akinesia
      and mydriasis in dogs.
AB  - The effect of local anaesthetic on the extraocular muscles was investigated in
      dogs by injecting lidocaine into the space between Tenon's capsule and the
      sclera. A cross-over design was used with both eyes from five Beagle dogs
      randomly injected, under general anaesthesia, with 1 mL of 2% lidocaine (1 mL
      lidocaine group), 2 mL of 2% lidocaine (2 mL-lidocaine group) or 2 mL of normal
      saline (control group). Each eye was assigned to all treatments with a minimum 14
      day interval between injections. Changes in eye position, pupil diameter, and
      intraocular pressure (IOP) were evaluated during the procedure. All eyes in the 2
      mL-lidocaine group exhibited akinesia and mydriasis (pupil diameter >10mm) with
      an onset time of 6.5 +/- 4.9 and 4.2 +/- 4.3 min, respectively. In the 1 mL
      lidocaine group, akinesia was induced in nine eyes and mydriasis occurred in
      seven eyes at 10.7 +/- 5.8 and 5.4 +/- 2.4 min after the injection, respectively.
      No changes in eye position or pupil diameter were observed in the control group.
      Akinesia was maintained for 44.3 +/- 26.7 min in the 1 mL-lidocaine group and for
      88.5 +/- 17.2 min in the 2 mL-lidocaine group. Duration of mydriasis was 51.7 +/-
      28.9 min in the 1 mL-lidocaine group and 82.9 +/- 15.6 min in the 2 mL-lidocaine
      group. Marked chemosis and sub-conjunctival haemorrhage occurred in 16/30 and
      15/30 eyes, respectively. No significant change in IOP was observed between the
      mean pre- and post-injection values in all groups. These results suggest that a
      sub-Tenon's injection of 2 mL of 2% lidocaine provided effective extraocular
      muscle akinesia and mydriasis in dogs.

PMID- 23000007
TI  - Vaccines for vector control: exciting possibilities for the future.

PMID- 23000008
TI  - Nanotoxicity and the importance of being earnest.

PMID- 23000009
TI  - Oligobenzylethylenimine enriches linear polyethylenimine with a pH-sensitive
      membrane-disruptive property and leads to enhanced gene delivery activity.
AB  - We report here the synthesis of a diblock linear polymer of
      oligo(benzylethylenimine)-b-polyethylenimine (OBzEI-PEI) and investigate its gene
      delivery properties. The linear copolymer OBzEI-PEI was prepared in a
      straightforward manner by acidic hydrolysis of a diblock polyoxazoline, which had
      been made by sequential polymerization of 4-benzyl-2-ethyl-2-oxazoline followed
      by 2-ethyl-2-oxazoline. pH titration and DNA complexation profiles of the new
      polymer are similar to regular linear PEIs, but with higher gene transfection
      efficiencies in various cell lines despite a decreased cellular uptake of plasmid
      DNA. Further experiments suggest that the OBzEI tail complements the intrinsic
      proton-sponge endosomolytic activities of PEI with an acid pH-sensitive membrane
      perturbing activity.

PMID- 23000011
TI  - Colony stimulating factors and myeloid cell biology in health and disease.
AB  - The colony stimulating factors (CSFs), granulocyte macrophage-CSF (GM-CSF),
      macrophage-CSF (M-CSF or CSF-1) and granulocyte-CSF (G-CSF) were first identified
      as in vitro hematopoietic growth factors. They have since been shown to regulate
      myeloid cell numbers and function at steady state and during inflammation.
      Preclinical data suggest that targeting CSFs might be beneficial in autoimmune
      and inflammatory disease, and manipulation of CSF biology is now being tested in
      clinical trials. Here, we examine recent insights into CSF function, at steady
      state and during pathology, as provided by CSF or CSF receptor
      neutralization/deletion studies or from CSF administration. We discuss
      controversies regarding the role of CSFs in controlling specific myeloid cell
      populations and highlight how the newly identified M-CSF receptor ligand,
      interleukin (IL)-34, is necessitating a reassessment of the field.

PMID- 23000010
TI  - Immunity's fourth dimension: approaching the circadian-immune connection.
AB  - The circadian system ensures the generation and maintenance of self-sustained ~24
      h rhythms in physiology that are linked to internal and environmental changes. In
      mammals, daily variations in light intensity and other cues are integrated by a
      hypothalamic master clock that conveys circadian information to peripheral
      molecular clocks that orchestrate physiology. Multiple immune parameters also
      vary throughout the day and disruption of circadian homeostasis is associated
      with immune-related disease. Here, we discuss the molecular links between the
      circadian and immune systems and examine their outputs and disease implications.
      Understanding the mechanisms that underlie circadian-immune crosstalk may prove
      valuable for devising novel prophylactic and therapeutic interventions.

PMID- 23000012
TI  - Variable stiffness actuated prosthetic knee to restore knee buckling during
      stance: a modeling study.
AB  - Most modern intelligent knee prosthesis use dampers to modulate dynamic behavior
      and prevent excessive knee flexion, but they dissipate energy and do not assist
      in knee extension. Energy efficient variable stiffness control (VSA) can reduce
      the energy consumption yet effectively modulate the dynamic behavior and use
      stored energy during flexion to assist in subsequent extension. A principle
      design of energy efficient VSA in a prosthetic knee is proposed and analyzed for
      the specific case of rejection of a disturbed stance phase. The concept is based
      on the principle that the output stiffness of a spring can be changed without
      changing the energy stored in the elastic elements of the spring. The usability
      of this concept to control a prosthetic knee is evaluated using a model. Part of
      the stance phase of the human leg was modeled by a double pendulum. Specifically
      the rejection of a common disturbance of transfemoral prosthetic gait, an
      unlocked knee at heel strike, was evaluated. The ranges of spring stiffnesses
      were determined such that the angular characteristics of a normal stance phase
      were preserved, but disturbances could also be rejected. The simulations
      predicted that energy efficient VSA can be useful for the control of prosthetic
      knees.

PMID- 23000013
TI  - Exposure to nerve agents: from status epilepticus to neuroinflammation, brain
      damage, neurogenesis and epilepsy.
AB  - Epilepsy is a common neurological disorder characterized by an initial injury due
      to stroke, traumatic brain injury, brain infection, or febrile seizures causing
      status epilepticus (SE). This phenomenon precedes recurrent (secondary) seizures,
      the latent period (period without seizures) and downstream appearance of
      spontaneous recurrent seizures (SRS). Epilepsy inducers include the
      organophosphorous (OP) compounds modified as chemical warfare nerve agents, such
      as soman. SE induced by soman is a result of cholinergic system hyperactivity
      caused by the irreversible inhibition of acetylcholinesterase, and the subsequent
      increase in the amount of the neurotransmitter acetylcholine at central and
      peripheral sites. SE leads to profound, permanent, complex and widespread brain
      damage and associated cognitive and behavioral deficits, accompanied by impaired
      neurogenesis. Several anticonvulsant and neuroprotective strategies have been
      studied in order to avoid the epileptogenesis which occurs after SE caused by
      soman exposure. In recent studies, we showed that SRS occur post-soman exposure
      and neuropathology can be reduced with diazepam (DZP) and valproic acid (VPA)
      when administered in combination treatment. These effects are accompanied by
      neurogenesis seen 15 days post-exposure in the hippocampal dentate gyrus (DG).
      This review discusses several findings about epilepsy induced by soman exposure
      such as behavioral changes, EEG anomalies, neuropathology, neuroinflammation,
      neurogenesis, possible circuitry changes and current strategies for treatment.
      The soman seizure model is an important model of temporal lobe epilepsy (TLE) and
      comparable in certain respects with well studied models in the literature such as
      pilocarpine and kainic acid. All these models together allow for a greater
      understanding of the different mechanisms of seizure induction, propagation and
      options for treatment. These studies are very necessary for current military and
      civilian treatment regimens, against OP nerve agent exposure, which fail to
      prevent SE resulting in severe neuropathology and epilepsy.

PMID- 23000014
TI  - Individual brain-frequency responses to self-selected music.
AB  - Music is a stimulus which may give rise to a wide range of emotional and
      cognitive responses. Therefore, brain reactivity to music has become a focus of
      interest in cognitive neuroscience. It is possible that individual preference
      moderates the effectof music on the brain. In the present study we examined
      whether there are common effects of listening to music even if each subject in a
      sample chooses their own piece of music. We invited 18 subjects to bring along
      their favorite relaxing music, and their favourite stimulating music.
      Additionally, a condition with tactile stimulation on the foot and a baseline
      condition (rest) without stimulation were used. The tactile stimulation was
      chosen to provide a simple, non-auditory condition which would be identical for
      all subjects. The electroencephalogram was recorded for each of the 3 conditions
      and during rest. We found responses in the alpha range mainly on parietal and
      occipital sites that were significant compared to baseline in 13 subjects during
      relaxing music, 15 subjects during activating music, and 16 subjects during
      tactile stimulation. Most subjects showed an alpha desynchronization in a lower
      alpha range followed by a synchronization in an upper frequency range. However,
      some subjects showed an increase in this area, whereas others showed a decrease
      only. In addition, many subjects showed reactivity in the beta range. Beta
      activity was especially increased while listening to activating music and during
      tactile stimulation in most subjects. We found interindividual differences in the
      response patterns even though the stimuli provoked comparable subjective emotions
      (relaxation, activation), and even if the stimulus was the same for all subjects
      (somatosensory stimulation). We suggest that brain responsivity to music should
      be examined individually by considering individual characteristics.

PMID- 23000015
TI  - Program running versus problem solving: two patterns of cardiac response.
AB  - Our previous research showed that mental tasks that involve program running (RUN
      tasks), e.g. performing arithmetic operations, cause greater tonic increase in
      cardiovascular activity than tasks that require a search for problem solutions
      (EDIT tasks), e.g. logical completion of a series of digits. However, it was not
      clear what physiological mechanism was responsible for this difference. The aim
      of the experiment was to compare cardiac response patterns while solving three
      mental tasks matched for their duration and level of difficulty: a simple RT task
      (control task) and two numerical tasks: RUN and EDIT. Forty-eight males,
      university students, divided randomly into three groups (n=16), participated in
      the experiment. Each group performed a different task. Task-evoked changes in
      heart rate (HR), strong volume (SV), cardiac output (CO), pre-ejection period
      (PEP), and power of HF component of heart rate variability were subject of the
      analysis. The results showed a higher tonic HR increase during the RUN task than
      the two other tasks and larger shortening of PEP during the RUN than the EDIT
      task. The HF power was larger during the RT task than the RUN task. No
      significant between-task difference was found in SV and CO changes. The results
      seem to support the hypothesis that higher cardiac responsiveness to RUN than
      EDIT tasks is mainly due to the difference in sympathetic activation.

PMID- 23000016
TI  - Differentially expressed transcripts from leaf and root tissue of Chlorophytum
      borivilianum: a plant with high medicinal value.
AB  - Chlorophytum borivilianum is one of the important medicinal plants used for
      treating different health problems such as diabetes, arthritis, physical
      weakness, etc. Saponins present in C. borivilianum are the primary source of its
      significant medicinal properties and are synthesized by mevalonate and non
      mevalonate pathways in plants. However, the biosynthesis of these compounds at
      molecular level is not studied in C. borivilianum. Cloning and sequencing of
      genes involved in metabolic processes are prerequisite to study the gene
      expression, their regulation and genetic engineering experiments. Expressed
      sequence tags (ESTs) provide a quick insight into various genes and their tissue
      specific expression. Suppression subtractive hybridization (SSH) libraries were
      constructed using mRNA from leaf and root tissues of C. borivilianum. High
      quality non-redundant 506 and 303 ESTs were generated from leaf and root specific
      libraries respectively. These sequences were analyzed using bioinformatics tools
      and grouped into different categories based on their similarity and cellular
      functions such as photosynthesis, metabolism, transcription factors, cell
      signaling, defense, stress response etc. ESTs also showed similarity with genes
      involved in saponins biosynthesis such as squalene synthase, squalene epoxidase,
      cytochrome p450, glycosyltransferase, etc. Semi-quantitative analysis of some of
      the ESTs involved in saponins biosynthesis confirmed their differential
      regulation in leaves and roots. These ESTs will provide an efficient resource to
      accelerate gene discovery in C. borivilianum and will help in determining
      promising targets for genetic engineering of saponins pathway.

PMID- 23000017
TI  - Mosaicism for trisomy 21 and ring (21) in a male born to normal parents: a case
      report.
AB  - We present a case of a ring (21) in a mentally challenged patient with mosaicism
      for trisomy 21 showing karyotype 47, XY,+21/47,XY,+21(r)/46,XY, born to normal
      parents. The parents and female sibling were phenotypically normal. This is a
      unique case report from Central India, on occurrence of trisomy 21 and r (21) in
      the same individual born to normal parents. Also being documented for the first
      time is the immuno-FISH analysis revealing differential expression of hTERT and a
      linked over expression of TRF2 in proband, probably corresponding to a high
      percentage of acrocentric associations.

PMID- 23000018
TI  - Monoclonal antibody to serum immunoglobulins of Clarias batrachus and its
      application in immunoassays.
AB  - Serum immunoglobulins of Clarias batrachus (Cb-Ig) were purified by affinity
      chromatography using bovine serum albumin as capture ligand. Under reducing
      conditions in SDS-PAGE, Cb-Ig was composed of a heavy (H) chain (68.7 kDa) and
      two light (L) chains (27.4 and 26.3 kDa). Purified Cb-Ig was used to produce a
      monoclonal antibody (MAb) designated E4 MAb that belonged to IgG1 subclass. In
      Western blotting, this MAb showed binding to H chain of purified Cb-Ig and
      putative H chains in reduced sera of C. batrachus, Clarias gariepinus and
      Heteropneustes fossilis. However, no binding was observed with serum protein of
      Labeo rohita and Channa striata. Cross-reactivity of anti-Cb-Ig MAb was observed
      with serum of C. batrachus, C. gariepinus and H. fossilis in competitive ELISA.
      In immunoblotting of non-reduced Cb-Ig with E4 MAb, four bands assumed to be
      tetrameric, trimeric, dimeric and monomeric form were observed. In flow
      cytometric analysis of the gated lymphocytes, the number of surface Ig-positive
      (Ig+) cells in blood, spleen, kidney and thymus of C. batrachus was determined to
      be 50.1 +/- 3.1, 55.1 +/- 3.36, 42.4 +/- 4.81 and 5.1 +/- 0.89%, respectively,
      using E4 MAb. Ig+ cells were also demonstrated in formalin-fixed paraffin
      embedded tissue sections of spleen, kidney, thymus and smears of blood
      mononuclear cells in indirect immunoperoxidase test. The developed MAb was
      employed to detect pathogen-specific immunoglobulins in the sera of C. batrachus
      immunized with killed Edwardsiella tarda, by an indirect ELISA. This monoclonal
      antibody can be useful tool in immunological research and assays.

PMID- 23000019
TI  - Promoter CpG methylation status in porcine Lyn is associated with its expression
      levels.
AB  - Resistance to disease and improvement of product quality are important goals in
      pig farming. Tyrosine Protein Kinase Lyn (LYN) is one of several Src-family
      tyrosine kinases in immune cells. This protein functions both as a positive and
      negative regulator of B cell activation, and regulates signaling pathways through
      phosphorylation of inhibitory receptors, enzymes and adaptors, which suggested
      that LYN could be correlated with immunity and can be considered as a candidate
      gene to study in disease resistance. Until now, the profiles of expression and
      transcriptional regulation of the LYN gene in pig breeds different in immune
      capacity remain unclear. Using real-time PCR, it indicated that porcine LYN mRNA
      expressed mainly in immune organs including the spleen, duodenum and liver.
      Furthermore, Dahuabai pigs (a kind of Chinese indigenous pig breeds with higher
      immune capacity) showed significant higher LYN mRNA expression levels than that
      in Landrace. Methylation analysis indicates that LYN expression levels were
      associated with the methylation status of the LYN promoter, and methylation of
      the novel CpG site at -1268C/-1267G generated by transposition at -1267 (A->G)
      results in up-regulating transcriptional activity of this gene. Interestingly,
      the base A located in -1267 mainly exhibited in landrace while the base G mainly
      in Dahuabai pigs. These results might contribute to study the function of this
      gene in pig breeding for disease resistance.

PMID- 23000020
TI  - Identification of a novel CCM2 gene mutation in an Italian family with multiple
      cerebral cavernous malformations and epilepsy: a causative mutation?
AB  - Cerebral cavernous malformations (CCMs; OMIM 116860) are vascular anomalies
      mostly located in the central nervous system (CNS) and occasionally within the
      skin and retina. Main clinical manifestations are seizure, hemorrhage, recurrent
      headaches, focal neurological deficits and epileptic attacks. The CCMs can occur
      as sporadic or autosomal dominant conditions, although with incomplete penetrance
      and variable clinical expression. Familial CCMs were associated with causative
      mutations in the CCM1 [K-Rev interaction trapped 1 (KRIT1)], CCM2 (MGC4607) and
      CCM3 (PDCD10) genes. This study reports the identification of a previously
      undescribed deletion mutation in CCM2 gene exon 5, in an Italian family with
      multiple cerebral cavernous malformations and epilepsy. Mutation c.502_503delAG
      results in a frame shift causing a TGA stop codon. This truncates the mutant CCM2
      gene protein, the malcavernin, to 233 amino acids, respect to 444 amino acids of
      the wild-type malcavernin. By using real-time RT-PCR, we have found that the mRNA
      resulting from two nucleotides deletion showed a 70% reduction relative to the
      wild-type transcript, indicating that it may be subject to a degradation
      mechanism such as nonsense-mediated decay (NMD).

PMID- 23000021
TI  - Isolation and nucleotide sequence analysis of the of Rhinella arenarum beta
      catenin: an mRNA and protein expression study during the larval stages of the
      digestive tract development.
AB  - beta-catenin interacts with several proteins mediating key biological processes,
      such as cadherin-mediated cell-cell adhesion as well as signal transduction. This
      work was done to establish the molecular basis and regulation of the formation
      pattern of cadherin/beta-catenin-mediated adherens junctions, using an animal
      model of unknown gene sequence, the toad Rhinella arenarum. A Rhinella arenarum
      beta-catenin homolog was isolated from larval tissue, their sequence compared and
      analyzed with those of eight other vertebrates using bioinformatics tools. The
      mRNA and protein expression levels of beta-catenin were determined during the
      development of Rhinella arenarum digestive tract both by Reverse Transcriptase
      Polymerase Chain Reaction (RT-PCR) and immunohistochemistry-morphometry
      respectively. Using Xenopus laevis frog specific primers, a fragment 539 bp of
      Rhinella arenarum toad beta-catenin cDNA was obtained and sequenced. The
      resulting putative sequence of 177 amino acids showed high similarity at the
      amino acid level (97%) when compared to other six vertebrates (Xenopus laevis,
      Xenopus tropicalis, Mus musculus, Rattus norvegicus, Bos taurus and Homo
      sapiens), with sequences and structural domains characteristic of catenins.
      Subsequently, using primers specifically designed for Rhinella arenarum
      nucleotide sequence, beta-catenin-mRNA increasing levels were found during the
      Rhinella arenarum metamorphosis. Finally, increasing beta-catenin protein
      expression during development has confirmed the specificity the detection of
      Rhinella arenarum beta-catenin. Summarizing, we have isolated and sequenced a
      beta-catenin-homologue sequence from the Rhinella arenarum toad, which is highly
      conserved between species, and following we have detected beta-catenin mRNA and
      protein levels during their digestive tract development.

PMID- 23000022
TI  - Impaired ion channel function related to a common KCNQ1 mutation - implications
      for risk stratification in long QT syndrome 1.
AB  - Long QT syndrome (LQTS) 1 is the most common type of inherited LQTS and is linked
      to mutations in the KCNQ1 gene. We identified a KCNQ1 missense mutation, KCNQ1
      G325R, in an asymptomatic patient presenting with significant QT prolongation
      (QTc, 448-600ms). Prior clinical reports revealed phenotypic variability ranging
      from the absence of symptoms to syncope among KCNQ1 G325R mutation carriers. The
      present study was designed to determine the G325R ion channel phenotype and its
      association with the clinical LQTS presentation. Electrophysiological testing was
      performed using the Xenopus oocyte expression system. KCNQ1 G325R channels were
      non-functional and suppressed wild type (WT) currents by 71.1%. In the presence
      of the native cardiac regulatory beta-subunit, KCNE1, currents conducted by G325R
      and WT KCNQ1 were reduced by 52.9%. Co-expression of G325R and WT KCNQ1 with
      KCNE1 shifted the voltage-dependence of I(Ks) activation by 12.0mV, indicating co
      assembly of mutant and WT subunits. The dysfunctional biophysical phenotype
      validates the pathogenicity of the KCNQ1 G325R mutation and corresponds well with
      the severe clinical presentation revealed in some reports. However, the index
      patient and other mutation carriers were asymptomatic, highlighting potential
      limitations of risk assessment schemes based on ion channel data.

PMID- 23000023
TI  - GC content dependency of open reading frame prediction via stop codon
      frequencies.
AB  - A frequently used approach for detecting potential coding regions is to search
      for stop codons. In the standard genetic code 3 out of 64 trinucleotides are stop
      codons. Hence, in random or non-coding DNA one can expect every 21st
      trinucleotide to have the same sequence as a stop codon. In contrast, the open
      reading frames (ORFs) of most protein-coding genes are considerably longer. Thus,
      the stop codon frequency in coding sequences deviates from the background
      frequency of the corresponding trinucleotides. This has been utilized for gene
      prediction, in particular, in detecting protein-coding ORFs. Traditional methods
      based on stop codon frequency are based on the assumption that the GC content is
      about 50%. However, many genomes show significant deviations from that value.
      With the presented method we can describe the effects of GC content on the
      selection of appropriate length thresholds of potentially coding ORFs.
      Conversely, for a given length threshold, we can calculate the probability of
      observing it in a random sequence. Thus, we can derive the maximum GC content for
      which ORF length is practicable as a feature for gene prediction methods and the
      resulting false positive rates. A rough estimate for an upper limit is a GC
      content of 80%. This estimate can be made more precise by including further
      parameters and by taking into account start codons as well. We demonstrate the
      feasibility of this method by applying it to the genomes of the bacteria
      Rickettsia prowazekii, Escherichia coli and Caulobacter crescentus, exemplifying
      the effect of GC content variations according to our predictions. We have adapted
      the method for predicting coding ORFs by stop codon frequency to the case of GC
      contents different from 50%. Usually, several methods for gene finding need to be
      combined. Thus, our results concern a specific part within a package of methods.
      Interestingly, for genomes with low GC content such as that of R. prowazekii, the
      presented method provides remarkably good results even when applied alone.

PMID- 23000024
TI  - Changes in spatial memory and BDNF expression to simultaneous dietary restriction
      and forced exercise.
AB  - Previous literature suggests that learning and memory formation can be influenced
      by diet and exercise. In the current study, we investigated the combined effects
      of forced swimming exercise (FSE) and every other day fasting (EODF) on spatial
      memory formation and on the levels of brain-derived neurotrophic factor (BDNF) in
      the hippocampus of Wistar male rats. The radial arm water maze (RAWM) paradigm
      was used to assess changes in learning and memory formation, whereas ELISA assay
      was used to measure BDNF protein levels. The FSE and/or EODF were simultaneously
      instituted for 6 weeks. Results show that FSE improved learning, short-term as
      well as long-term memory formation, and significantly increased BDNF protein in
      the hippocampus (p<0.05). However, EODF had no effect on either spatial learning
      and memory formation or the levels of hippocamapal BDNF protein (p>0.05). In
      addition, EODF did not modulate beneficial effect of swimming exercise on
      cognitive function (p>0.05). Thus exercise enhanced, while EODF did not affect
      spatial learning and memory formation.

PMID- 23000026
TI  - A comparison of food policy and practice reporting between credentialed and
      noncredentialed Ohio school foodservice directors.
AB  - With rising childhood obesity rates and the increasing complexity of the school
      food environment, practitioners working in school nutrition need adequate
      preparation for their responsibilities. School foodservice directors (SFSDs) vary
      widely in their academic preparation, and there are no established standards for
      individuals in this occupation. Credentialing provides a way in which baseline
      knowledge of SFSDs can be established; however, little is known about the
      influence of such credentials on food-related policies and practices in public
      schools. Our cross-sectional study compared the reported food policies and
      practices between credentialed and noncredentialed SFSDs within all districts
      (N=364) of the Ohio public school system during the 2009-2010 school year. Using
      a Likert-type format, policy and practice scores were measured by asking
      participants to respond to statements adapted from the School Health Index
      assessment tool. Differences in the policy and practice scores reported by SFSDs
      holding a food-related credential and those not holding a credential were
      determined by t test. Results indicated that respondents with a food-related
      credential were more likely to report both comprehensive food-related policies
      (14.51 vs 13.39; range=0 to 21) and practices (33.86 vs 32.50; range=0 to 39).
      These findings support the value of credentialing SFSDs. However, further
      research is required to establish which credential provides the optimal match in
      the provision of high quality nutrition care to schoolchildren.

PMID- 23000025
TI  - Determinants and consequences of adherence to the dietary approaches to stop
      hypertension diet in African-American and white adults with high blood pressure:
      results from the ENCORE trial.
AB  - BACKGROUND: Although the Dietary Approaches to Stop Hypertension (DASH) diet is
      an accepted nonpharmacologic treatment for hypertension, little is known about
      what patient characteristics affect dietary adherence and what level of adherence
      is needed to reduce blood pressure (BP). OBJECTIVE: Our aim was to determine what
      factors predict dietary adherence and the extent to which dietary adherence is
      necessary to produce clinically meaningful BP reductions. DESIGN: Ancillary study
      of the ENCORE (Exercise and Nutrition Interventions for Cardiovascular Health)
      trial--a 16-week randomized clinical trial of diet and exercise.
      PARTICIPANTS/SETTING: Participants included 144 sedentary, overweight, or obese
      adults (body mass index 25 to 39.9) with high BP (systolic 130 to 159 mm Hg
      and/or diastolic 85 to 99 mm Hg). INTERVENTION: Patients were randomized to one
      of three groups: DASH diet alone, DASH diet plus weight management, and Usual
      Diet Controls. MAIN OUTCOMES MEASURES: Our primary outcomes were a composite
      index of adherence to the DASH diet and clinic BP. STATISTICAL ANALYSES
      PERFORMED: General linear models were used to compare treatment groups on post
      treatment adherence to the DASH diet. Linear regression was used to examine
      potential predictors of post-treatment DASH adherence. Analysis of covariance was
      used to examine the relation of adherence to the DASH diet and BP. RESULTS:
      Participants in the DASH diet plus weight management (16.1 systolic BP [SBP]; 95%
      CI 13.0 to 19.2 mm Hg and 9.9 diastolic BP [DBP]; 95% CI 8.1 to 11.6 mm Hg) and
      DASH diet alone (11.2 SBP; 95% CI 8.1 to 14.3 mm Hg and 7.5 DBP; 95% CI 5.8 to
      9.3 mm Hg) groups showed significant reductions in BP in comparison with Usual
      Diet Controls participants (3.4 SBP; 95% CI 0.4 to 6.4 mm Hg and DBP 3.8; 95% CI
      2.2 to 5.5 mm Hg). Greater post-treatment consumption of DASH foods was noted in
      both the DASH diet alone (mean = 6.20; 95% CI 5.83 to 6.57) and DASH diet plus
      weight management groups (mean = 6.23; 95% CI 5.88 to 6.59) compared with Usual
      Diet Controls (mean = 3.66; 95% CI 3.30 to 4.01; P<0.0001), and greater adherence
      to the DASH diet was associated with larger reductions in clinic SBP and DBP (P
      <= 0.01). Only ethnicity predicted dietary adherence, with African Americans less
      adherent to the DASH diet compared with whites (4.68; 95% CI 4.34 to 5.03 vs
      5.83; 95% CI 5.50 to 6.11; P<0.001). CONCLUSIONS: Greater adherence to the DASH
      diet was associated with larger BP reductions independent of weight loss. African
      Americans were less likely to be adherent to the DASH dietary eating plan
      compared with whites, suggesting that culturally sensitive dietary strategies
      might be needed to improve adherence to the DASH diet.

PMID- 23000027
TI  - Entomopathogenic fungi as potential biocontrol agents of the ecto-parasitic mite,
      Varroa destructor, and their effect on the immune response of honey bees (Apis
      mellifera L.).
AB  - Three isolates of each of the entomopathogenic fungi, Metarhizium anisopliae,
      Beauveria bassiana and Clonostachys rosea, were assessed for their pathogenicity
      to the honey bee parasitic mite, Varroa destructor. The fungi were applied to
      varroa mites by immersing them in a spore solution, and then the inoculated mites
      were placed on honey bee brood inside capped cells. At 7 days post inoculation
      (dpi), the three fungi caused significant varroa mortality compared to non
      inoculated mites. In brood treated only with varroa mites, expression of the
      honey bee genes, hymenoptaecin and poly U binding factor 68 Kd (pUf68), decreased
      over time, while expression of blue cheese (BlCh) and single minded (SiMd) was
      not affected. In brood inoculated directly only with M. anisopliae or B.
      bassiana, the emerged adults showed reduced weight indicating infection by the
      fungi, which was confirmed by observation of hyphae in the brood. Fungal
      infection of the brood resulted in increased expression of hymenoptaecin, pUf68
      and BlCh, but not SiMd. In brood treated with varroa mites that had been
      inoculated with the fungi, expression of hymenoptaecin, pUf68 and BlCh, but not
      SiMd, was even more up-regulated. While varroa mites can suppress gene expression
      in honey bee brood, varroa mites infected with entomopathogenic fungi induced
      their expression. This may be due to a low level of fungal infection of the bee,
      which negated the immunosuppression by the mites. Therefore, entomopathogenic
      fungi could reduce varroa mite damage to honey bee brood by both infecting the
      parasite and preventing varroa-associated suppression of honey bee immunity.

PMID- 23000028
TI  - Neural progenitor cells derived from adult bone marrow mesenchymal stem cells
      promote neuronal regeneration.
AB  - AIM: It is well known that neural stem/progenitor cells (NS/PC) are an ideal cell
      type for the treatment of central nervous system (CNS) disease. However, ethical
      problems have severely hampered fetal NS/PC from being widely used as a source
      for stem cell therapy. Recently, it has been demonstrated that autologous bone
      marrow mesenchymal stem cells (BMSC) can transdifferentiate into neural
      progenitor cells (NPC). The biological function of BMSC derived NPC (MDNPC) in
      neuronal systems remains unknown. In the present study, we aimed to investigate
      whether MDNPC can promote in vitro neural regeneration, a process comprising
      mainly the generation of neurons and neurotransmitters. MAIN METHODS: We co
      cultured BMSC, MDNPC or fetal NS/PC with PC12 cells and studied their roles on
      proliferation, neurite formation and dopamine release from PC12 cells.
      Furthermore, we also explored the mechanisms by which MDNPC regulate dopamine
      secretion from PC12 derived neural cells using Western blot. KEY FINDINGS: We
      found that both MDNPC and NS/PC had similar morphologies and there were no
      significant differences between MDNPC and NS/PC in promoting PC12 cell
      proliferation, neurite outgrowth, and dopamine release. We also demonstrated that
      NS/PC induced dopamine secretion was associated with an upregulation of dopamine
      transporter (DAT) levels. SIGNIFICANCE: In summary, MDNPC were comparable to
      NS/PC in promoting neural regeneration, indicating that MDNPC are a promising
      candidate source of neural stem cells for the treatment of neurological diseases.

PMID- 23000029
TI  - Presence of functional angiotensin II receptor and angiotensin converting enzyme
      in the aorta of the snake Bothrops jararaca.
AB  - AIM: Angiotensin II (Ang II) interacts with AT(1) and AT(2) receptors and, in
      some vertebrates, with an Ang II binding site showing low affinity for AT(1) and
      AT(2) receptor antagonists. This study was carried out to characterize the Ang II
      receptor, and the presence of an angiotensin-converting enzyme (ACE) in the aorta
      of the Bothrops jararaca snake. MAIN METHOD: Contraction induced by Ang I or II
      in aortic ring from the snake was evaluated in the absence or in the presence of
      ACE-blocker or Ang II antagonists. KEY FINDINGS: Ang II analogs, modified at
      positions 1 and 5, induced vasoconstriction with differences in their potencies.
      The relative rank order was: [Asp(1), Val(5)] Ang II=[Asp(1), Ile(5)] Ang
      II>>>[Asn(1), Val(5)] Ang II. ACE-like activity was detected, as well as an Ang
      II receptor with low affinity for AT(1) and AT(2) selective receptor antagonists
      (pK(B) values of 5.62+/-0.23 and 5.08+/-0.25). A disulfide reducing agent almost
      abolished the Ang II effect, while an alpha adrenoceptor antagonist, or removing
      the endothelium, did not modify the Ang II effect. These results indicate that
      the B. jararaca aorta has an Ang II receptor pharmacologically distinct from
      AT(1) and AT(2) receptors, and the vasoconstrictor effect observed is independent
      of catecholamine or endothelium modulation. ACE and the AT receptor in the aorta
      of B. jararaca may be part of a tissue renin-angiotensin system. SIGNIFICANCE:
      The data contribute to the knowledge of the renin-angiotensin system in
      vertebrate species, and provide insight into the understanding of snake Ang II
      receptor characteristics and diversity.

PMID- 23000030
TI  - Interleukin-1 beta simultaneously affects the stress and reproductive axes by
      modulating norepinephrine levels in different brain areas.
AB  - AIMS: Interleukin-1beta (IL-1beta) is a cytokine that is known to activate the
      stress axis and suppress the reproductive axis. Different brain areas are
      involved in the regulation of these two axes. However, they are both under the
      stimulatory control of the catecholamine, norepinephrine (NE). Here, we
      hypothesized that IL-1beta differentially affects these two axes by modulating NE
      levels in specific brain regions. MAIN METHODS: Female Sprague-Dawley rats in
      proestrus were injected intraperitoneally with either PBS-1.0% BSA (control) or
      5MUg of IL-1beta at 1pm. Groups of rats were sacrificed at 1, 3, and 5pm and
      their brains were collected. Brain areas associated with reproduction as well as
      areas associated with stress axis activity were isolated and analyzed for NE
      concentrations using HPLC-EC. Trunk blood was analyzed for IL-1beta,
      corticosterone and luteinizing hormone levels. KEY FINDINGS: As a general trend,
      treatment with IL-1beta significantly decreased NE levels (p<0.05) in the areas
      controlling reproductive functions when compared to the control group. In
      contrast, NE levels increased significantly (p<0.05) in the stress associated
      areas. LH levels were markedly decreased with IL-1beta treatment while
      corticosterone levels increased dramatically. SIGNIFICANCE: The ability of IL
      1beta to produce differential effects on the stress and reproductive axis could
      be explained by modulation of NE levels in specific brain areas that are
      associated with these functions. This differential regulation of NE may be an
      adaptive phenomenon in response to a systemic immune challenge.

PMID- 23000031
TI  - Red fluorescent proteins: chromophore formation and cellular applications.
AB  - In the last decade, a number of red fluorescent proteins (RFPs) that emit orange,
      red, and far-red fluorescence have been isolated from anthozoans (corals), and
      developed through directed molecular evolution. An attractive property possessed
      by some RFPs is that their red fluorescence can be turned on or modulated by
      illumination at specific wavelengths. Recent progress in the development of RFPs
      has been accompanied with detailed studies of chromophore chemistry. A thorough
      understanding of the molecular mechanisms involved in the post-translational
      modifications of red chromophores would enable scientists to design RFPs with the
      desired properties to advance imaging applications. This article provides a broad
      perspective on the chemistry and applications of RFPs.

PMID- 23000032
TI  - Functional dynamics of proteins revealed by solution NMR.
AB  - Solution NMR spectroscopy can analyze the dynamics of proteins on a wide range of
      timescales, from picoseconds to even days, in a site-specific manner, and thus
      its results are complementary to the detailed but largely static structural
      information obtained by X-ray crystallography. We review recent progresses in a
      variety of NMR techniques, including relaxation dispersion and paramagnetic
      relaxation enhancement (PRE), that permit the observation of the low-populated
      states, which had been 'invisible' with other techniques. In addition, we review
      how NMR spectroscopy can be used to elucidate functionally relevant protein
      dynamics.

PMID- 23000033
TI  - Glyceraldehyde-3-phosphate dehydrogenase regulates cyclooxygenase-2 expression by
      targeting mRNA stability.
AB  - Cyclooxygenase (COX)-2 is an inducible inflammatory protein whose expression is
      partially regulated at the post-transcriptional level. We investigated whether
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binds to the AU-rich element
      (ARE) of COX-2 mRNA for its degradation. Knockdown of GAPDH in hepa1c1c7 cells
      significantly enhanced COX-2 expressions. Recombinant GAPDH bound to the COX-2
      ARE within the first 60 nucleotides of the 3'-UTR via the NAD(+) binding domain.
      Interestingly, a C151S GAPDH mutant retained binding activity. Confocal
      microscopy observation revealed that LPS exposure reduced the localization of
      GAPDH in nuclei. Our results indicate that GAPDH negatively regulates COX-2 by
      binding to its ARE.

PMID- 23000035
TI  - Adult post-traumatic radioulnar synostosis.
AB  - Post-traumatic radioulnar synostosis is a rare complication of forearm fracture.
      Resulting in loss of forearm axial rotation, it is functionally very disabling.
      The surgical indication, timing of operation, surgical technique, interest and
      type of adjuvant treatment are all issues with which physicians managing
      radioulnar synostosis must deal. No therapeutic consensus yet exists, but a wide
      variety of surgical techniques and adjuvant treatments are suggested. A
      literature review sought to identify risk factors for synostosis, with a view to
      prevention and determining a suitable therapeutic attitude in the light of
      existing data.

PMID- 23000034
TI  - Crystal structure of cytochrome P450 CYP105N1 from Streptomyces coelicolor, an
      oxidase in the coelibactin siderophore biosynthetic pathway.
AB  - The genome sequence of Streptomyces coelicolor contains 18 cytochrome P450
      enzymes. The recombinant CYP105N1 protein has been expressed in Escherichia coli
      and purified, and we report the biochemical and structural characterization of
      CYP105N1 from S. coelicolor. The purified protein exhibited the typical CO
      binding spectrum of P450 enzymes and type I binding spectra with estradiol and a
      coelibactin analog. The oxidation of estradiol by CYP105N1, supported by
      H(2)O(2), produced estriol. The crystal structure of CYP105N1 was determined at
      2.9 A resolution. An unexpected wide open binding pocket located above the heme
      group was identified, with a volume of approximately 4299 A(3). These results
      suggest that the large open pocket to the active site may be a key feature for
      easy access of the peptidyl carrier protein-bound substrate to perform the
      hydroxylation reaction. A molecular docking model with coelibactin showed that
      the phenyl group of coelibactin is located <4 A away from the heme-iron,
      suggesting that CYP105N1 may be involved in the hydroxylation of the phenyl ring
      of the coelibactin precursor during biosynthesis.

PMID- 23000036
TI  - Vascularized proximal fibular epiphyseal transfer: two cases.
AB  - Vascularized proximal fibular epiphyseal transfer in children enables
      reconstruction of long-bone epiphyseal defect, while conserving axial growth
      potential. This technique was applied in two children for diaphyseal-epiphyseal
      reconstruction of the proximal humerus and distal radius respectively, using a
      graft vascularized only by the anterior tibial artery. There were no major
      complications during harvesting. Both cases showed transplant growth, of a mean
      0.5cm/year. Joint function in the proximal humerus reconstruction was
      satisfactory, with functional range of motion. In the distal radius
      reconstruction, range of motion was almost zero; insufficient transplant growth
      induced radial club hand, requiring partial correction by progressive lengthening
      using an external fixator. In case of severe bone loss, fibular epiphyseal
      diaphyseal graft vascularized only by the anterior tibial artery is a feasible
      attitude.

PMID- 23000037
TI  - Analysis of segmental residual growth after progressive bone lengthening in
      congenital lower limb deformity.
AB  - INTRODUCTION: The issue of prognosis in limb length discrepancy in children
      affected by congenital abnormality remains a subject of concern. Therapeutic
      strategy must take length prediction into account, to adapt equalization
      techniques and the timing of treatment. Initial prognosis, however, may need
      revising after completion of one or several surgical interventions on the
      pathologic limb. The aim of this study was to determine the different types of
      growth response that a bone segment can present after progressive lengthening in
      case of congenital limb length discrepancy. MATERIALS AND METHODS: A series of
      114 bone lengthenings with external fixator, performed in 36 girls and 50 boys
      with congenital lower limb length discrepancy, was retrospectively analyzed. Bone
      segment growth rates were measured before lengthening, during the first year
      after frame removal and finally over long-term follow-up, calculating the ratios
      of radiological bone length to the number of months between two measurements.
      Mean follow-up was 4.54+/-0.2 years. RESULTS: Changes in short- and long-term
      growth rate distinguished five patterns of bone behavior after lengthening,
      ranging from growth acceleration to total inhibition. DISCUSSION: These five
      residual growth patterns depended on certain factors causing acceleration or, on
      the contrary, slowing down of growth: age at the lengthening operation,
      percentage lengthening, and minimal period between two lengthenings. These
      criteria help optimize conditions for resumed growth after progressive segmental
      lengthening, avoiding conditions liable to induce slowing down or inhibition, and
      providing a planning aid in multi-step lengthening programs. LEVEL OF EVIDENCE:
      Level IV. Retrospective study.

PMID- 23000038
TI  - Operative treatment of clavicle midshaft fractures using a locking compression
      plate: comparison between mini-invasive plate osteosynthesis (MIPPO) technique
      and conventional open reduction.
AB  - HYPOTHESIS: The goal of the present study was to compare minimally invasive
      percutaneous plate osteosynthesis (MIPPO) technique and conventional open
      reduction with LCP for the treatment of clavicle midshaft fractures in adults in
      a randomized, controlled, clinical trial with a minimum of 1-year follow-up.
      MATERIALS AND METHODS: Between June 2006 and May 2008, 64 cases of open reduction
      and internal plate fixation were performed for clavicle midshaft fractures. The
      operative indications were complete displacement, severe comminution and marked
      shortening of the clavicle (>2cm). MIPPO and conventional open reduction surgery
      procedures with LCP were used in 32 and 32 cases, respectively. RESULTS: The mean
      time to union was 13 weeks in the open reduction group compared to 12 weeks in
      MIPPO group (P>0.05). The MIPPO group had no significantly superior Constant
      shoulder scores or DASH scores at all time-points (P>0.05). However, the
      complications in the open reduction group were dysesthesia in the area of the
      incision and directly below in 10 cases, hypertrophic scarring in five cases,
      painful shoulder in two cases and a limitation of shoulder motion in one case
      (P>0.05). The complications in the MIPPO group were dysesthesia in two cases, no
      hypertrophic scarring, no painful shoulder, no limitation of shoulder motion were
      noted (P<0.05). Patients in this operative group were more satisfied with
      cosmetic appearance and overall outcome than those in the conventional open
      reduction group. CONCLUSIONS: Operative treatment with a LCP for clavicle shaft
      fractures can be used to obtain stable fixation. Particularly, MIPPO of displaced
      midshaft clavicular fractures resulted in a lower rate of dysesthesia,
      hypertrophic scarring, and a better cosmetic than conventional open reduction,
      although the functional outcomes (Constant and DASH) were no different between
      the two groups. Overall satisfaction was higher in the MIPPO group than
      conventional open reduction group. LEVEL OF EVIDENCE: Level IV. Retrospective
      study.

PMID- 23000039
TI  - Epidemiology of proximal humerus fractures managed in a trauma center.
AB  - Proximal humerus fractures (PHF) are osteoporotic fractures that affect women
      over 70 years of age. Like fractures of the femoral neck they have become a
      public health concern. As the population ages there is an increase in the number
      of people in poor general condition with an increased risk of falls on fragile
      bones. The incidence of these fractures has increased by 15% per year. All
      patients managed for PHF in our center in the past year were included in this
      prospective study (prospective cohort study; level 2). Three hundred and twenty
      five patients were included with 329 fractures. There was a ratio of two women to
      one man. At the final follow-up 50 patients had died (15%) and 25 patients were
      lost to follow-up. The mean age was 70 years old. There were two types of risk
      factors. The first was fragile bones, and the second was patient specific risk of
      falls. The severity of the fracture increased with the age of the population. In
      the study by Charles S. Neer in 1970, 85% of PHF were not or were only slightly
      displaced, while this category percentage was only 42% in our study.
      Hospitalization was necessary in 43% of the cases in our study. Surgical
      management was necessary in 21%. This lack of relationship between the percentage
      of displaced fractures (58%) and the percentage of surgically treated fractures
      is a sign of the difficulties of managing this population, which is usually in
      poor general condition.

PMID- 23000041
TI  - Temporary left ventricular resynchronization therapy in cardiogenic shock: a new
      pacing paradigm to fight an old foe?

PMID- 23000040
TI  - QRS narrowing is associated with reverse remodeling in patients with chronic
      right ventricular pacing upgraded to cardiac resynchronization therapy.
AB  - BACKGROUND: Patients with chronic right ventricular pacing (RVP) upgraded to
      cardiac resynchronization therapy (CRT) have been excluded from the majority of
      clinical trials of CRT. Little is known about the predictors of response in this
      population. We hypothesized that reversal of RVP-induced electrical dyssynchrony
      (indexed by QRS duration) by CRT would predict a favorable response. OBJECTIVE:
      The purpose of this study was to identify baseline characteristics associated
      with response in patients upgraded to CRT from chronic RVP. METHODS: Consecutive
      patients presenting for CRT at the Cleveland Clinic between September 30, 2003,
      and July 8, 2008, with chronic RVP and serial echocardiograms were included in
      this analysis. RVP was defined as>85% pacing on a pre-CRT device check, previous
      AV nodal ablation, or complete pacer dependency per chart notes. Response was
      defined as a reduction in left ventricular end-systolic volume >= 15% from
      baseline. Clinical, ECG, and echocardiographic data were extracted to determine
      covariates associated with response. RESULTS: One hundred twelve patients met
      inclusion criteria, of whom 72 (64.3%) met criteria for response over median
      follow-up of 9.9 months (interquartile range [6.5-14.7]). No significant
      differences were noted in terms of male gender (68.1% vs 75.0%; P = .52),
      ischemic cardiomyopathy (55.6% vs 55.0%; P = 1), pre-CRT QRS duration (189.1 +/-
      20.7 ms vs 185.5 +/- 26.8 ms; P = .47), duration of RVP before CRT upgrade (5.8
      +/- 3.9 years vs 6.2 +/- 4.0 years; P = .57), or baseline left ventricular end
      systolic volume (160.0 +/- 60.7 mL vs 172.8 +/- 67.2 mL; P = .32) between
      responders and nonresponders, respectively. Percent reduction in QRS duration
      between the right ventricular-paced and first biventricular-paced waveforms was
      significantly greater in responders compared with nonresponders (14.4% +/- 13.2%
      vs 7.2%+/- 14.0%; P = .01). In multivariate analysis, percent reduction in QRS
      narrowing was the lone factor associated with response (odds ratio 0.02 [0.001
      0.42]; P = .01). CONCLUSION: Reversal of electrical dyssynchrony predicts
      response to CRT in chronically RV-paced patients upgraded to CRT. Traditional
      factors associated with a favorable response to CRT in de novo implants (female
      gender, nonischemic cardiomyopathy, and wider baseline QRS duration) are not
      significantly associated with response in upgraded patients. Duration of RVP
      before CRT upgrade is not an important determinant of response.

PMID- 23000042
TI  - Chunking: a procedure to improve naturalistic data analysis.
AB  - Every year, traffic accidents are responsible for more than 1,000,000 fatalities
      worldwide. Understanding the causes of traffic accidents and increasing safety on
      the road are priority issues for both legislators and the automotive industry.
      Recently, in Europe, the US and Japan, significant public funding has been
      allocated for performing large-scale naturalistic driving studies to better
      understand accident causation and the impact of safety systems on traffic safety.
      The data provided by these naturalistic driving studies has never been available
      before in this quantity and comprehensiveness and it promises to support a wide
      variety of data analyses. The volume and variety of the data also pose
      substantial challenges that demand new data reduction and analysis techniques.
      This paper presents a general procedure for the analysis of naturalistic driving
      data called chunking that can support many of these analyses by increasing their
      robustness and sensitivity. Chunking divides data into equivalent, elementary
      chunks of data to facilitate a robust and consistent calculation of parameters.
      This procedure was applied, as an example, to naturalistic driving data from the
      SeMiFOT study in Sweden and compared with alternative procedures from past
      studies in order to show its advantages and rationale in a specific example. Our
      results show how to apply the chunking procedure and how chunking can help avoid
      bias from data segments with heterogeneous durations (typically obtained from SQL
      queries). Finally, this paper shows how chunking can increase the robustness of
      parameter calculation, statistical sensitivity, and create a solid basis for
      further data analyses. 

PMID- 23000043
TI  - A diet containing the soy phytoestrogen genistein causes infertility in female
      rats partially deficient in UDP glucuronyltransferase.
AB  - Soy beans contain genistein, a natural compound that has estrogenic effects
      because it binds the estrogen receptor with relatively high affinity. Genistein
      is therefore the most important environmental estrogen in the human diet.
      Detoxification of genistein is mediated through conjugation by UDP
      glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a
      genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because
      our Gunn rats stopped breeding after the animal chow was changed to a type with
      much higher soy content, we examined the mechanism behind this soy diet induced
      infertility. Gunn and control rats were fed diets with and without genistein. In
      these rats, plasma levels of genistein and metabolites, fertility and
      reproductive parameters were determined. Enzyme assays showed reduced genistein
      UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were
      completely infertile on a genistein diet, wild type rats were fertile. Genistein
      diet caused a persistent estrus, lowered serum progesterone and inhibited
      development of corpora lutea in Gunn rats. Concentrations of total genistein in
      Gunn and control rat plasma were identical and within the range observed in
      humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated
      genistein, compared to 3.6% in control rats. This study shows that, under
      conditions of reduced glucuronidation, dietary genistein exhibits a strongly
      increased estrogenic effect. Because polymorphisms that reduce UGT1 expression
      are prevalent in the human population, these results suggest a cautionary
      attitude towards the consumption of large amounts of soy or soy supplements.

PMID- 23000045
TI  - Kinetic aspects and identification of by-products during the ozonation of
      bitertanol in agricultural wastewaters.
AB  - The degradation of bitertanol by ozone treatment is investigated. Solutions of
      bitertanol (8.4 MUg mL(-1)) were prepared either by dissolution of the standard
      or by dilution of Gaucho Ble seed loading solution and then ozonated under
      different conditions. Evolution of the concentrations of bitertanol and its
      ozonation by-products in both solutions was monitored by HPLC-UV as a function of
      the treatment time for a concentration of 100 gm(-3) of ozone in the inlet gas.
      Bitertanol degradation was found to follow a pseudo-first order reaction in both
      cases. However, the rate of the reaction in diluted seed loading solution was
      much lower (0.19 vs. 0.27 min(-1) in standard solution) and was close to the
      reaction rate observed in the presence of a radical scavenger, tert-butanol (0.11
      min(-1)). Thus, it may be suggested that additives present in the seed loading
      solution may play the role of radical scavengers. Study of ozone concentration in
      the inlet gas (from 25 to 100 gm(-3)) showed that ozone degradation is also a
      first-order reaction with respect to ozone. Four ozonation by-products were
      highlighted, collected and identified by HPLC coupled with an ion trap mass
      spectrometer using positive electrospray ionization mode. A degradation pathway
      of bitertanol was finally proposed.

PMID- 23000046
TI  - The effects of sub-lethal salinity concentrations on the anti-predator responses
      of fathead minnows.
AB  - Salinization, both natural and anthropogenic, of inland waters is a major facet
      of environmental change, and can have detrimental effects on aquatic systems.
      Fish facing increasing levels of salinity must do more than simply survive
      salinization, they must also undertake important behaviours such as predator
      avoidance. Here, we exposed fathead minnows (Pimephales promelas) to three levels
      of salinity crossed by three levels of predation risk cues. We found a reduction
      in pre-stimulus movement and a lowered intensity of anti-predator response for
      the highest salinity exposure (8000 ppm). We also found that the typical threat
      sensitive anti-predator response (an important behaviour conferring fitness
      advantages) was absent in the two highest salinity exposure treatments. Our data
      demonstrate that salinization can have negative effects on critical behaviours
      well below physiological tolerance levels.

PMID- 23000044
TI  - Deficiency in the nuclear factor E2-related factor 2 renders pancreatic beta
      cells vulnerable to arsenic-induced cell damage.
AB  - Chronic human exposure to inorganic arsenic (iAs), a potent environmental
      oxidative stressor, is associated with increased prevalence of type 2 diabetes,
      where impairment of pancreatic beta-cell function is a key pathogenic factor.
      Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor
      regulating cellular adaptive response to oxidative stress. However, persistent
      activation of Nrf2 in response to chronic oxidative stress, including inorganic
      arsenite (iAs3+) exposure, blunts glucose-triggered reactive oxygen species (ROS)
      signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current
      study, we found that MIN6 pancreatic beta-cells with stable knockdown of Nrf2
      (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout
      (Nrf2-/-) mice exhibited reduced expression of several antioxidant and
      detoxification enzymes in response to acute iAs3+ exposure. As a result, Nrf2-KD
      MIN6 cells and Nrf2-/- islets were more susceptible to iAs3+ and
      monomethylarsonous acid (MMA3+)-induced cell damage, as measured by decreased
      cell viability, augmented apoptosis and morphological change. Pretreatment of
      MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from
      iAs3+-induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant
      N-acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of
      iAs3+. The present study demonstrates that Nrf2-mediated antioxidant response is
      critical in the pancreatic beta-cell defense mechanism against acute cytotoxicity
      by arsenic. The findings here, combined with our previous results on the
      inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2
      plays paradoxical roles in pancreatic beta-cell dysfunction induced by
      environmental arsenic exposure.

PMID- 23000047
TI  - Sulfur and oxygen isotope tracing in zero valent iron based In situ remediation
      system for metal contaminants.
AB  - In the present study, controlled laboratory column experiments were conducted to
      understand the biogeochemical changes during the microbial sulfate reduction.
      Sulfur and oxygen isotopes of sulfate were followed during sulfate reduction in
      zero valent iron incubated flow through columns at a constant temperature of 20+/
      1 degrees C for 90 d. Sulfur isotope signatures show considerable variation
      during biological sulfate reduction in our columns in comparison to abiotic
      columns where no changes were observed. The magnitude of the enrichment in
      delta(34)S values ranged from 9.40/00 to 10.30/00 compared to initial value of
      2.30/00, having total fractionation deltaS between biotic and abiotic columns as
      much as 6.10/00. Sulfur isotope fractionation was directly proportional to the
      sulfate reduction rates in the columns. Oxygen isotopes in this experiment seem
      less sensitive to microbial activities and more likely to be influenced by
      isotopic exchange with ambient water. A linear relationship is observed between
      delta(34)S and delta(18)O in biotic conditions and we also highlight a good
      relationship between delta(34)S and sulfate reduction rate in biotic columns.

PMID- 23000048
TI  - Degradation and aquatic toxicity of naphthenic acids in oil sands process
      affected waters using simulated wetlands.
AB  - Oil sands process-affected waters (OSPWs) produced during the extraction of
      bitumen at the Athabasca Oil Sands (AOS) located in northeastern Alberta, Canada,
      are toxic to many aquatic organisms. Much of this toxicity is related to a group
      of dissolved organic acids known as naphthenic acids (NAs). Naphthenic acids are
      a natural component of bitumen and are released into process water during the
      separation of bitumen from the oil sand ore by a caustic hot water extraction
      process. Using laboratory microcosms as an analogue of a proposed constructed
      wetland reclamation strategy for OSPW, we evaluated the effectiveness of these
      microcosms in degrading NAs and reducing the aquatic toxicity of OSPW over a 52
      week test period. Experimental manipulations included two sources of OSPW (one
      from Syncrude Canada Ltd. and one from Suncor Energy Inc.), two different
      hydraulic retention times (HRTs; 40 and 400 d), and increased nutrient
      availability (added nitrate and phosphate). Microcosms with a longer HRT (for
      both OSPWs) showed higher reductions in total NAs concentrations (64-74% NAs
      reduction, p<0.05) over the test period, while nutrient enrichment appeared to
      have little effect. A 96 h static acute rainbow trout (Oncorhynchus mykiss)
      bioassay showed that the initial acute toxicity of Syncrude OSPW (LC50=67% v/v)
      was reduced (LC50>100% v/v) independent of HRT. However, EC20s from separate
      Microtox(r) bioassays were relatively unchanged when comparing the input and
      microcosm waters at both HRTs over the 52-week study period (p>0.05), indicating
      that some sub-lethal toxicity persisted under these experimental conditions. The
      present study demonstrated that given sufficiently long HRTs, simulated wetland
      microcosms containing OSPW significantly reduced total NAs concentrations and
      acute toxicity, but left behind a persistent component of the NAs mixture that
      appeared to be associated with residual chronic toxicity.

PMID- 23000049
TI  - The potential of implant augmentation in the treatment of osteoporotic distal
      femur fractures: a biomechanical study.
AB  - PURPOSE: Osteoporotic fractures of the distal femur are an underestimated and
      increasing problem in trauma and orthopaedic surgery. Therefore, this study
      investigates the biomechanical potential of implant augmentation in the treatment
      of these fractures. METHODS: Twelve osteoporotic surrogate distal femora were
      randomly assigned to the augmented or non-augmented group. All specimens were
      fixed using the LCP DF. In the augmented group additionally 1ml Vertecem V+ was
      injected in each screw hole before screw positioning. The construct represents an
      AO 33 A3 fracture. Biomechanical testing was performed as sinusoidal axial
      loading between 50 and 500N with 2Hz for 45,000 cycles, followed by loading
      between 50 and 750N until failure. RESULTS: The augmented group showed
      significant higher axial stiffness (36%). Additionally the displacement after
      45,000 cycles was 3.4 times lower for the augmented group (0.68+/-0.2mm vs.
      2.28+/-0.2mm). Failure occurred after 45,130 cycles (SD 99) in all of the non
      augmented specimens and in two specimens of the augmented group after 69,675
      cycles (SD 1729). Four of the augmented specimens showed no failure. The failure
      mode of all specimens in both groups was a medial cut-out. CONCLUSIONS: This
      study shows a promising potential of implant augmentation in the treatment of
      osteoporotic distal femur fractures.

PMID- 23000050
TI  - The exclusive use of coagulation factor concentrates enables reversal of
      coagulopathy and decreases transfusion rates in patients with major blunt trauma.
AB  - BACKGROUND: FFP and coagulation factor concentrates are used to correct trauma
      induced coagulopathy (TIC). However, data on coagulation profiles investigating
      effects of therapy are scarce. METHODS: This is an analysis of 144 patients with
      major blunt trauma ((ISS)>=15), who were enrolled in a prospective cohort study
      investigating characteristics and treatment of TIC. Patients who received
      fibrinogen concentrate and/or prothrombin complex concentrate alone (CF Group)
      were compared with those additionally receiving FFP transfusions (FFP Group).
      RESULTS: Sixty-six patients exclusively received CF, while 78 patients
      additionally received FFP. Overall, patients were comparable regarding age,
      gender and ISS (CF Group, ISS 37 (29, 50); FFP Group ISS 38 (33, 55), p=0.28).
      Patients treated with CF alone showed sufficient haemostasis and received
      significantly fewer units of red blood cells (RBC) and platelets than did those
      also receiving FFP [(RBC 2(0, 4) U vs. 9 (5, 12) U; platelets 0 (0, 0) U vs. 1
      (0, 2) U, p<0.001)]. In addition, fewer patients in the CF Group developed
      multiorgan failure (MOF) (18.2% vs. 37.2%, p=0.01) or sepsis (16.9% vs. 35.9%,
      p=0.014) than in the FFP Group. Propensity score-matching (n=28 pairs) used to
      reduce the impact of treatment selection confirmed that additional FFP
      administration showed no benefit in restoring haemostasis, but was associated
      with significantly higher transfusion rates for RBC and platelets. CONCLUSION:
      The use of CF alone effectively corrected coagulopathy in patients with severe
      blunt trauma and concomitantly decreased exposure to allogeneic transfusion,
      which may translate into improved outcome.

PMID- 23000051
TI  - Is there a difference in perioperative mortality between cemented and uncemented
      implants in hip fracture surgery?
AB  - INTRODUCTION: Although cemented implants have proven beneficial over uncemented
      implants for treatment of displaced sub-capital proximal femoral fractures, there
      are concerns regarding the haemodynamic consequence of using cemented implants in
      hip fracture patients. National Patient Safety Agency recently issued an alert
      regarding the use of cement in hip fracture surgery. We compared the incidence
      and pattern of 48 h perioperative mortality between patients receiving cemented
      and uncemented implants after hip fracture surgery. METHODS: Using data
      prospectively recorded in hospital care records, we retrospectively reviewed the
      case records of all patients who died in hospital following hip fracture surgery
      between January 2005 and April 2010. We recorded demographic variables, type of
      fracture, implant used, medical co-morbidity, seniority of operating surgeon and
      anaesthetist, perioperative haemodynamic status, time and cause of death.
      RESULTS: We identified 15 cases of perioperative death (PoD) over a 64-month
      period. PoD was 1% (15/1402). Eight of 15 deaths occurred following cemented
      hemiarthroplasty insertion. There were four cases of intra-operative death, two
      of them were following cemented hemiarthroplasty insertion. PoD following
      cemented hemiarthroplasty was 2.54% (8/314) and nil (0/168) following uncemented
      Austin-Moore hemiarthroplasty. Operations were performed by both trainees (six)
      and consultants (two). Both trainees (five) and consultants (three) anaesthetised
      the patients. None of the patients belonged to American Society of
      Anesthesiologists (ASA) I or II (ASA III 5 and IV 3). All patients had
      significant cardiovascular or pulmonary co-morbidity. Apart from the cases of
      immediate haemodynamic collapse and death, cemented implant insertion was
      followed by intra-operative haemodynamic instability in 2/15 and perioperative
      instability in 3/15 patients. Post-mortem was performed in 3/8 patients: 2/3
      demonstrated pulmonary embolism (PE), 1/3 bronchopneumonia. Of the rest, 3/5 had
      suspected myocardial infarction (MI). CONCLUSION: There was 1% risk of
      perioperative death after hip fracture surgery. Risk of perioperative death was
      significantly higher following cemented implant insertion. Mortality risk was
      exacerbated in patients with pre-existing cardiovascular morbidity and was
      independent of the seniority of the surgeon or the anaesthetist.

PMID- 23000052
TI  - Volar versus dorsal latest-generation variable-angle locking plates for the
      fixation of AO type 23C 2.1 distal radius fractures: a biomechanical study in
      cadavers.
AB  - INTRODUCTION: Anatomicaly preformed variable-angle locking plates are
      technologically mature and appear to be optimal for the fixation of distal radius
      fractures. However, there is still much argument about whether volar plating is
      equivalent to dorsal (buttressing) plating, especially in the management of intra
      articular extension fractures. This biomechanical study was performed to
      determine, in a simple intra-articular fracture model, whether dorsal or volar
      plate constructs would be more stable. MATERIALS AND METHODS: Six pairs of fresh
      frozen radii were examined with dual-energy absorptiometry (DXA) to determine
      their bone mineral density (BMD). An AO type 23 C2.1 fracture was created. Volar
      fixation was with a 2.4mm Variable-Angle LCP Two-Column Volar Distal Radius
      Plate; dorsal fixation was with two orthogonal 2.4 mm Variable-Angle LCP Dorsal
      Distal Radius Plates (both devices: Synthes, Oberdorf, Switzerland).
      Biomechanical testing used a proven protocol involving static tests of stiffness,
      and a cyclic test to obtain range of motion (ROM), maximum deformation, and
      subsidence data. RESULTS: None of the constructs failed during biomechanical
      testing. The two groups (volar and dorsal plating, respectively) did not differ
      significantly in terms of initial (pre-cyclic-testing) and final (post-cyclic
      testing) stiffness. Equally, there was no significant difference between the
      subsidence values in the two groups. The post-cyclic-testing ROM was
      significantly greater in the dorsal-plate group as compared with the volar-plate
      group. The volar constructs showed a significant decrease in the ROM between pre-
      and post-cyclic testing. CONCLUSION: Biomechanically, volar plating with a modern
      variable-angle locking plate is equivalent to dorsal plating with two modern
      variable-angle locking plates.

PMID- 23000053
TI  - Preliminary study of the feasibility and accuracy of percutaneous peri-acetabular
      screw insertion in a porcine model.
AB  - The aim of this pilot study was to assess a new method of training for peri
      acetabular screw placement under indirect vision using standard C-arm fluoroscopy
      using a porcine model. Two novice orthopaedic residents placed 72 screws (36
      each) about the acetabula of six porcine pelves under C-arm fluoroscopic
      guidance. Unsatisfactory screw position was noted in 22 of 72, with five
      instances of screw ingress into the hip joint. All of these cases occurred in the
      first half of each resident's series. Screw direction and final position improved
      over subsequent trials. This pilot study demonstrates that surgical simulation
      techniques are applicable in percutaneous screw fixation. Such an approach could
      be useful for both residents in training and more experienced surgeons who wish
      to perform this procedure in cases where it is appropriate.

PMID- 23000054
TI  - Bone remodelling biomarkers after whole body cryotherapy (WBC) in elite rugby
      players.
AB  - Whole body cryotherapy (WBC) consists of a brief exposure to extreme cold air (
      110 degrees C) in a controlled chamber and it is applied in sports medicine to
      improve recovery from musculoskeletal trauma. The aim of this study is to better
      define the beneficial effect of WCB on the musculoskeletal system of athletes, in
      particular on bone remodelling. Remodelling osteoimmunological biomarkers OPG,
      RANKL and RANK were measured after WBC treatment in 10 male rugby players
      randomly selected from the Italian National team. OPG levels were increased
      significantly, supporting the view that WBC induces an osteogenic effect. Further
      studies evaluating the effect of WBC on bone metabolism are desirable. 

PMID- 23000055
TI  - Reliability of injury grading systems for patients with blunt splenic trauma.
AB  - OBJECTIVES: The most widely used grading system for blunt splenic injury is the
      American Association for the Surgery of Trauma (AAST) organ injury scale. In 2007
      a new grading system was developed. This 'Baltimore CT grading system' is
      superior to the AAST classification system in predicting the need for angiography
      and embolization or surgery. The objective of this study was to assess inter- and
      intraobserver reliability between radiologists in classifying splenic injury
      according to both grading systems. METHODS: CT scans of 83 patients with blunt
      splenic injury admitted between 1998 and 2008 to an academic Level 1 trauma
      centre were retrospectively reviewed. Inter and intrarater reliability were
      expressed in Cohen's or weighted Kappa values. RESULTS: Overall weighted
      interobserver Kappa coefficients for the AAST and 'Baltimore CT grading system'
      were respectively substantial (kappa=0.80) and almost perfect (kappa=0.85).
      Average weighted intraobserver Kappa's values were in the 'almost perfect' range
      (AAST: kappa=0.91, 'Baltimore CT grading system': kappa=0.81). CONCLUSION: The
      present study shows that overall the inter- and intraobserver reliability for
      grading splenic injury according to the AAST grading system and 'Baltimore CT
      grading system' are equally high. Because of the integration of vascular injury,
      the 'Baltimore CT grading system' supports clinical decision making. We therefore
      recommend use of this system in the classification of splenic injury.

PMID- 23000056
TI  - An antibody to the GM1/GalNAc-GD1a complex correlates with development of pure
      motor Guillain-Barre syndrome with reversible conduction failure.
AB  - Antibodies to a ganglioside complex consisting of GM1 and GalNAc-GD1a (GM1/GalNAc
      GD1a) are found in sera from patients with Guillain-Barre syndrome (GBS). To
      elucidate the clinical significance of anti-GM1/GalNAc-GD1a antibodies in GBS,
      clinical features of 58 GBS patients with IgG anti-GM1/GalNAc-GD1a antibodies
      confirmed by enzyme-linked immunosorbent assay and thin layer chromatography
      immunostaining were analyzed. Compared to GBS patients without anti-GM1/GalNAc
      GD1a antibodies, anti-GM1/GalNAc-GD1a-positive patients more frequently had a
      preceding respiratory infection (n=38, 66%, p<0.01) and were characterized by
      infrequency of cranial nerve deficits (n=9, 16%, p<0.01) and sensory disturbances
      (n=26, 45%, p<0.01). Of the 28 anti-GM1/GalNAc-GD1a-positive patients for whom
      electrophysiological data were available, 14 had conduction blocks (CBs) at
      intermediate segments of motor nerves, which were not followed by evident
      remyelination. Eight of 10 bedridden cases were able to walk independently within
      one month after the nadir. These results show that the presence of anti
      GM1/GalNAc-GD1a antibodies correlated with pure motor GBS characterized by
      antecedent respiratory infection, fewer cranial nerve deficits, and CBs at
      intermediate sites of motor nerves. The CB may be generated through alteration of
      the regulatory function of sodium channels in the nodal axolemma.

PMID- 23000057
TI  - Differing attitudes toward phenobarbital use in the neonatal period among
      neonatologists and child neurologists in Sweden.
AB  - OBJECTIVE: In spite of its known negative effects on brain development,
      phenobarbital is the most commonly used drug for neonatal seizures. We conducted
      a national survey among neonatologists and child neurologists to determine the
      variation in practice and attitudes. METHODS: Surveys were sent to all board
      certified child neurologists and neonatologists in Sweden as well as to residents
      in subspecialty training. In addition to questions concerning respondent
      demographic characteristics, the survey contained questions related to overall
      attitudes and practices and specific patient scenarios. RESULTS: Responses were
      obtained from 170 physicians (corresponding to approximately 50% of all eligible
      respondents). We found a high level of agreement concerning the initiation of
      treatment of neonatal seizures, as well as choice of first- (phenobarbital) and
      second-line (midazolam) drugs. In contrast, third-line drug choice differed
      between specialties, with neurologists being more prone to use levetiracetam or
      other drugs. Neonatologists were more likely to treat premature infants
      differently. For continued phenobarbital treatment there was less agreement among
      respondents. Whereas almost 75% of neonatologists felt that phenobarbital should
      "seldom" or "never" be used in long term treatment following neonatal seizures, a
      majority of child neurologists indicated "often" or "always". The same pattern
      was seen in responses to individual scenarios. CONCLUSION: The discrepancies
      between different specialties involved in treating neonatal seizures may reflect
      differences in training, but is also likely due to the lack of uniform
      guidelines. This highlights the importance of designing and carrying out clinical
      trials determining optimal treatment of neonatal seizures.

PMID- 23000058
TI  - Longevity-promoting effects of 4-hydroxy-E-globularinin in Caenorhabditis
      elegans.
AB  - In modern times, there has been a major increase in the use of plants or herbal
      constituents for the prevention of age-related disorders. 4-Hydroxy-E
      globularinin (4-HEG) is an iridoid and a major component of Premna integrifolia.
      This investigation represents a breakthrough in geriatrics by showing the
      longevity-promoting activity of 4-HEG in the animal model Caenorhabditis elegans.
      4-HEG (20MUM) enhanced the mean life span of worms by over 18.8% under normal
      culture conditions and also enhanced their survival under oxidative stress. The
      longevity-promoting activity was associated with reduced reactive oxygen species
      (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies
      verified the role of ROS detoxification pathways and simultaneous nuclear
      translocation of DAF-16 in the 4-HEG-mediated effects. Quantitative real-time PCR
      estimations and observations of transcriptional reporters indicated that 4-HEG
      was able to upregulate stress-inducible genes, viz., hsp-16.2 and sod-3. Thus, 4
      HEG may serve as a lead compound of plant origin for the development of important
      nutraceuticals superseding the aging process.

PMID- 23000059
TI  - Estrogen receptor potentiates mTORC2 signaling in breast cancer cells by
      upregulating superoxide anions.
AB  - The estrogen receptor (ER) plays a cardinal role in estrogen-responsive breast
      carcinogenesis. It is, however, unclear as to how estrogen-ER interaction
      potentiates breast cancer progression. Compelling evidence supports estrogen
      induced redox alterations, such as augmented reactive oxygen species (ROS)
      levels, as having a crucial role in breast carcinogenesis. Despite ER being a
      biological mediator of the majority of estrogen-induced cellular responses; its
      role in estrogen-induced tissue-specific ROS generation remains largely
      debatable. We examined a panel of human breast cancer specimens and found that ER
      positive breast cancer specimens exhibited a higher incidence of augmented O(2)(*
      ) levels compared to matched normal tissue. ROS are known to function as signal
      transducers and ROS-mediated signaling remains a key complementary mechanism that
      drives carcinogenesis by activating redox-sensitive oncogenic pathways.
      Additional studies revealed that augmented O(2)(*-) levels in breast cancer
      specimens coincided with mammalian target of rapamycin complex 2 (mTORC2)
      hyperactivation. Detailed investigations using in vitro experiments established
      that 17beta-estradiol (E2)-stimulated breast cancer cells exhibited transiently
      upregulated O(2)(*-) levels, with the presence of ER being a crucial determinant
      for the phenomenon to take place. Gene expression, ER transactivation, and
      confocal studies revealed that the E2-induced transient O(2)(*-) upregulation was
      effected by ER through a nongenomic pathway possibly involving mitochondria.
      Furthermore, E2 treatment activated mTORC2 in breast cancer cells in a
      characteristically ER-dependent manner. Interestingly, altering O(2)(*-) anion
      levels through chemical/genetic methods caused significant modulation of the
      mTORC2 signaling cascade. Taken together, our findings unravel a novel nongenomic
      pathway unique to estrogen-responsive breast cancer cells wherein, upon
      stimulation by E2, ER may regulate mTORC2 activity in a redox-dependent manner by
      transiently modulating O(2)(*-) levels particularly within mitochondria. The
      findings suggest that therapies aimed at counteracting these redox alterations
      and/or resultant signaling cascades may complement conventional treatments for
      estrogen-responsive breast cancer.

PMID- 23000061
TI  - Cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the
      E46K mutation in the alpha synuclein gene.
AB  - OBJECTIVE: The aim of this study was to analyze autonomic function and cardiac
      sympathetic innervation in symptomatic and asymptomatic carriers of the E46K
      alpha-synuclein gene (SNCA) mutation. PATIENTS AND METHODS: Autonomic function
      tests were performed in six patients, four of whom were symptomatic carriers
      (ages: 46, 59, 52 and 28-years) and two who were asymptomatic carriers (ages: 52
      and 29 years). Autopsy studies were performed on an additional two symptomatic
      carriers not eligible for autonomic testing. Patients completed the SCOPA
      autonomic questionnaire, and underwent the head-up tilt test accompanied by
      measurements of plasma norepinephrine. Valsalva maneuver and deep breathing
      tests, along with recording of sympathetic skin response (SSR) and cardiac MIBG
      scintigraphy were carried out. Myocardial tissue sections removed from the two
      autopsied cases were subjected to routine histological staining and
      immunohistochemical processing with monoclonal antibodies against tyrosine
      hydroxylase and alpha-synuclein. RESULTS: Both the four symptomatic and the older
      asymptomatic carriers reported abnormalities in the SCOPA questionnaire and had
      markedly diminished cardiac MIBG uptake. Plasma norepinephrine in the supine and
      tilted positions was normal in all subjects. Only one patient had significant
      orthostatic hypotension. There was a complete absence of tyrosine hydroxylase
      immunostaining in the myocardium of the two autopsied cases. INTERPRETATION: We
      have found imaging and histological evidence of cardiac sympathetic denervation
      in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene
      mutation. The sympathetic denervation appears to be organ-specific, with
      selective affectation of the heart given that plasma norepinephrine levels and
      blood pressure were normal.

PMID- 23000060
TI  - Manganese superoxide dismutase interacts with a large scale of cellular and
      mitochondrial proteins in low-dose radiation-induced adaptive radioprotection.
AB  - The cellular adaptive response to certain low-level genotoxic stresses, including
      exposure to low-dose ionizing radiation (LDIR), shows promise as a tool to
      enhance radioprotection in normal cells but not in tumor cells. Manganese
      superoxide dismutase (MnSOD), a fundamental mitochondrial antioxidant in
      mammalian cells, plays a key role in the LDIR-induced adaptive response. In this
      study, we aimed to elucidate the signaling network associated with MnSOD-induced
      radiation protection. A MnSOD-interacting protein profile was established in LDIR
      treated human skin cells. Human skin keratinocytes (HK18) were irradiated with a
      single dose of LDIR (10 cGy X-ray) and the cell lysates were immunoprecipitated
      using alpha-MnSOD and applied to two different gel-based proteomic experiments
      followed by mass spectrometry for protein identification. Analysis of the
      profiles of MnSOD-interacting partners before and after LDIR detected various
      patterns of MnSOD protein-protein interactions in response to LDIR.
      Interestingly, many of the MnSOD-interacting proteins are known to have functions
      related to mitochondrial regulation of cell metabolism, apoptosis, and DNA
      repair. These results provide evidence indicating that in addition to the
      enzymatic action of detoxifying superoxide, the antioxidant MnSOD may function as
      a signaling regulator in stress-induced adaptive protection through cell survival
      pathways.

PMID- 23000062
TI  - Pleiotrophin promotes microglia proliferation and secretion of neurotrophic
      factors by activating extracellular signal-regulated kinase 1/2 pathway.
AB  - Pleiotrophin (PTN) is an effective neuroprotective factor and its expression is
      strikingly increased in microglia after ischemia/reperfusion injury. However,
      whether PTN could provide neurotrophic support to neurons by regulating microglia
      function is not clear. In this study, we demonstrated that the expression of PTN
      was induced in microglia after oxygen-glucose deprivation/reperfusion. PTN
      promoted the proliferation of microglia by enhancing the G1 to S phase
      transition. PTN also stimulated the secretion of brain-derived neurotrophic
      factor (BDNF), ciliary neurotrophic factor (CNTF) and nerve growth factor (NGF)
      in microglia, but did not upregulate the expression of proinflammatory factors
      such as TNF-alpha, IL-1beta and iNOS. Mechanistically, we found that PTN
      increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2
      in microglia in both concentration-dependent and time-dependent manners. In
      addition, ERK1/2 inhibitor U0126 abolished the proliferation and G1 to S phase
      transition of microglia stimulated by PTN, and inhibited the production of BDNF,
      CNTF and NGF induced by PTN. In conclusion, our results demonstrated that PTN
      ERK1/2 pathway plays important role in regulating microglia growth and secretion
      of neurotrophic factors. These findings provide new insight into the
      neuroprotective role of PTN and suggest that PTN is a new target for therapeutic
      intervention of stroke.

PMID- 23000063
TI  - Influence of penetration enhancer on drug permeation from volatile formulations.
AB  - Previously we have reported the influence of supersaturation on the permeation of
      fentanyl across model membranes and skin. The findings indicated that the vehicle
      and, specifically its residence time in skin, influence the ability of the
      formulation to enhance membrane drug permeation. The aim of the present study was
      to probe the role of vehicle components on (trans)dermal drug delivery in more
      detail. To this end, three commonly used chemical penetration enhancers were
      selected for investigation namely, propylene glycol (PG), octyl salicylate (OSAL)
      and isopropyl myristate (IPM). A further objective was to clarify the mechanism
      of action of OSAL. Model spray formulations were prepared consisting of 10% (v/v)
      of individual enhancers in ethanol. Saturated and supersaturated systems were
      evaluated for their ability to promote fentanyl transport across human skin in
      vitro. Mass balance studies and determination of the extent of uptake of
      enhancers by skin were also conducted. The results indicated that increasing the
      degree of drug saturation (DS) does not promote drug permeation for formulations
      in PG but increasing drug DS did promote drug permeation for IPM and some OSAL
      systems. This probably reflects faster depletion of PG compared with IPM and
      OSAL. Non-linear modelling of the permeation data indicated that PG and IPM act
      to promote drug solubility in the membrane whereas OSAL appears to act as a skin
      penetration enhancer by increasing drug diffusivity in the skin.

PMID- 23000064
TI  - Neurogenic differentiation of human adipose-derived stem cells: relevance of
      different signaling molecules, transcription factors, and key marker genes.
AB  - Since numerous diseases affect the central nervous system and it has limited self
      repair capability, a great interest in using stem cells as an alternative cell
      source is generated. Previous reports have shown the differentiation of adipose
      derived stem cells in neuron-like cells and it has also been proved that the
      expression pattern of patterning, proneural, and neural factors, such as Pax6,
      Mash1, Ngn2, NeuroD1, Tbr2 and Tbr1, regulates and defines adult neurogenesis.
      Regarding this, we hypothesize that a functional parallelism between adult
      neurogenesis and neuronal differentiation of human adipose-derived stem cells
      exists. In this study we differentiate human adipose-derived stem cells into
      neuron-like cells and analyze the expression pattern of different patterning,
      proneural, neural and neurotransmitter genes, before and after neuronal
      differentiation. The neuron-like cells expressed neuronal markers, patterning and
      proneural factors characteristics of intermediate stages of neuronal
      differentiation. Thus we demonstrated that it is possible to differentiate
      adipose-derived stem cells in vitro into immature neuron-like cells and that this
      process is regulated in a similar way to adult neurogenesis. This may contribute
      to elucidate molecular mechanisms involved in neuronal differentiation of adult
      human non-neural cells, in aid of the development of potential therapeutic tools
      for diseases of the nervous system.

PMID- 23000065
TI  - Effect of periplasmic expression of recombinant mouse interleukin-4 on hydrogen
      peroxide concentration and catalase activity in Escherichia coli.
AB  - Oxidative stress occurs as a result of imbalance between generation and
      detoxification of reactive oxygen species (ROS). This kind of stress was rarely
      discussed in connection with foreign protein production in Escherichia coli.
      Relation between cytoplasmic recombinant protein expression with H(2)O(2)
      concentration and catalase activity variation was already reported. The
      periplasmic space of E. coli has different oxidative environment in relative to
      cytoplasm and there are some benefits in periplasmic expression of recombinant
      proteins. In this study, hydrogen peroxide concentration and catalase activity
      following periplasmic expression of mouse IL-4 were measured in E. coli. After
      construction of pET2mIL4 plasmid, the expression of recombinant mouse interleukin
      4 (mIL-4) was confirmed. Then, the H(2)O(2) concentration and catalase activity
      variation in the cells were studied in exponential and stationary phases at
      various ODs and were compared to those of wild type cells and empty vector
      transformed cells. It was revealed that empty vector introduction and periplasmic
      recombinant protein expression increased significantly the H(2)O(2) concentration
      of the cells. However, the H(2)O(2) concentration in mIL-4 expressing cells was
      significantly higher than its concentration in empty vector transformed cells,
      demonstrating more effects of recombinant mIL-4 expression on H(2)O(2) elevation.
      Likewise, although catalase activity was reduced in foreign DNA introduced cells,
      it was more lowered following expression of recombinant proteins. Correlation
      between H(2)O(2) concentration elevation and catalase activity reduction with
      cell growth depletion is also demonstrated. It was also found that recombinant
      protein expression results in cell size increase.

PMID- 23000066
TI  - Isolation and characterization of a bread wheat salinity responsive ERF
      transcription factor.
AB  - A screen conducted on both a suppression subtractive hybridization and a full
      length cDNA library made from a salinity tolerant bread wheat cultivar SR3
      (Triticum aestivum cv. SR3) resulted in the recognition of TaERF4, a gene
      including both an AP2/ERF domain and a nuclear localization signal. The 982 bp
      TaERF4 cDNA comprised a 582 bp open reading frame, encoding a 193 residue
      polypeptide of molecular weight 20 kDa and calculated pI 8.48. A TaERF4-GFP
      fusion protein localized preferentially to the nuclei of Arabidopsis thaliana
      protoplasts. TaERF4 is a member of the B-1 group within the ERF sub-family and
      was not transactivatable in yeast. The presence of an ERF-associated amphiphilic
      repression (EAR) motif at its C-terminus suggests that TaERF4 is probably a
      transcription repressor. TaERF4 was inducible by exposure to salinity and osmotic
      stresses, but not to exogenously supplied abscisic acid (ABA). The heterologous
      constitutive expression of TaERF4 in Arabidopsis enhanced the level of
      sensitivity to salinity stress, possibly via the repression of tonoplast
      Na(+)/H(+) antiporter activity. There was no phenotype associated with the
      transgene's presence when plants were subjected to either osmotic stress or ABA
      treatment. TaERF4 appears to be a transcription repressor acting within the ABA
      independent response to salinity stress.

PMID- 23000067
TI  - A novel type heterozygous mutation in the glucose-6-phosphatase gene in a Chinese
      patient with glycogen storage disease Ia.
AB  - Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen
      storage disease type Ia (GSD Ia). By genotype analysis of the affected pedigree,
      we identified a novel type mutation in a Chinese patient with GSD Ia. Mutation
      analysis was performed for the coding region of G6Pase gene using DNA sequencing
      and TaqMan gene expression assay was used to further confirm the novel mutation.
      The proband was compound heterozygous for c.311A>T/c.648G>T. Our report expands
      the spectrum of G6Pase gene mutation in China.

PMID- 23000068
TI  - DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the
      susceptibility to pediatric immune thrombocytopenic purpura in Egypt.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized
      by increased platelet destruction. Although the etiology of ITP remains unclear,
      it is accepted that both environmental and genetic factors play an important role
      in the development of the disease. The present study aimed at exploring a novel
      molecular determinant that may influence the susceptibility and course of ITP in
      Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor
      polymorphism by polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP
      patients and 150 age and gender matched healthy controls. The results obtained
      revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients
      and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79).
      There was no statistically significant difference between ITP patients with wild
      or mutant genotypes as regards their clinical or laboratory data. Furthermore,
      there was no statistical difference in the distribution of DNMT3B -579G>T
      genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T
      promotor polymorphism represents a novel genetic risk factor for ITP but not a
      predictor for tendency to chronicity in pediatric ITP in Egypt.

PMID- 23000069
TI  - A novel heterozygous mutation of the AIRE gene in a patient with autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED).
AB  - BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      syndrome (APECED) is an autosomal recessive disease due to mutations of the
      autoimmune regulator (AIRE) gene. Typical manifestations include candidiasis,
      Addison's disease, and hypoparathyroidism. Type 1 diabetes, alopecia, vitiligo,
      ectodermal dystrophy, celiac disease and other intestinal dysfunctions, chronic
      atrophic gastritis, chronic active hepatitis, autoimmune thyroid disorders,
      pernicious anemia and premature ovarian failure are other rare associated
      diseases although other conditions have been associated with APECED. CASE
      PRESENTATION: What follows is the clinical, endocrinological and molecular data
      of a female APECED patient coming from Lithuania. The patient was affected by
      chronic mucocutaneous candidiasis, hypoparathyroidism and pre-clinical Addison's
      disease. Using direct sequencing of all the 14 exons of the AIRE gene in the
      patient's DNA, we identified in exon 6 the known mutation c.769 C>T (p.Arg257X)
      in compound heterozygosity with the newly discovered mutation c.1214delC
      (p.Pro405fs) in exon 10. The novel mutation results in a frameshift that is
      predicted to alter the sequence of the protein starting from amino acid 405 as
      well as to cause its premature truncation, therefore a non-functional Aire
      protein. CONCLUSIONS: A novel mutation has been described in a patient with
      APECED with classical clinical components, found in compound heterozygosity with
      the c.769 C>T variation. Expanded epidemiological investigations based on AIRE
      gene sequencing are necessary to verify the relevancy of the novel mutation to
      APECED etiopathogenesis in the Lithuanian population and to prove its diagnostic
      efficacy in association with clinical and immunological findings.

PMID- 23000070
TI  - Computational centrosomics: an approach to understand the dynamic behaviour of
      centrosome.
AB  - Centrosomes are the key regulating element of cell cycle progression. Aberrations
      in their functional mechanism leads to several cancer related disorders. Although
      genomic studies in the field of centrosome have been extensively carried out,
      with the lack of structural conformation, the proteomic analysis of pathological
      genetic mutation is still a challenging task. Several computational algorithms
      and high range force fields are used to design the 3D structure conformation of
      proteins, which has now become the leading platform for in-silico drug discovery
      approaches. Application of these highly efficient platforms in centrosomics
      studies will be a novel approach to develop an efficient drug therapy for the
      treatment of their dysfunction disorders.

PMID- 23000071
TI  - Evolutionary patterns of the mitochondrial genome in the Moorish gecko, Tarentola
      mauritanica.
AB  - A previous study on the evolutionary patterns of Tarentola mauritanica
      demonstrated that low levels of mitochondrial diversity observed in the European
      populations relative to nuclear markers were consistent with a selective sweep
      hypothesis. In order to unravel the mitochondrial evolutionary history in this
      European population and two other lineages of T. mauritanica (Iberian and North
      African clades), variation within 22 nearly complete mitogenomes was analyzed.
      Surprisingly, each clade seems to have a distinct evolutionary history; with both
      the European and Iberian clades presenting a decrease of polymorphism, which in
      the former is consistent with departure from neutrality of the mtDNA (positive or
      background selection), but in the latter seems to be the result of a bottleneck
      after a population expansion. The pattern exhibited by the North African clade
      seems to be a consequence of adaptation to certain mtDNA variants by positive
      selection.

PMID- 23000072
TI  - Can diffusion-weighted magnetic resonance imaging (DW-MRI) alone be used as a
      reliable sequence for the preoperative detection and characterisation of hepatic
      metastases? A meta-analysis.
AB  - PURPOSE: To perform a meta-analysis of all available studies of the diagnostic
      performance of diffusion-weighted magnetic resonance imaging (DW-MRI) in patients
      with hepatic metastases. METHODS: Databases including MEDLINE and EMBASE were
      searched for relevant original articles published from January 2000 to February
      2012. We determined sensitivities and specificities across studies, calculated
      positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio
      (DOR) and constructed summary receiver operating characteristic curves using
      hierarchical regression models. RESULTS: Across 11 studies (537 patients), DW-MRI
      sensitivity was 0.87 (95%confidence interval (CI), 0.80, 0.91) and specificity
      was 0.90 (95%CI, 0.86, 0.93). Overall, LR+ was 8.52 (95%CI, 6.17, 11.77), LR- was
      0.15 (95%CI, 0.10, 0.22) and DOR was 57.36 (95%CI, 38.29, 85.93). In studies in
      which both DW-MRI and contrast-enhanced magnetic resonance imaging (CE-MRI) were
      performed, the comparison of DW-MRI performance with that of CE-MRI suggested no
      major differences against these two methods (p>0.05). DW-MRI combined CE-MRI had
      higher sensitivity and specificity than DW-MRI alone (97% versus 86% and 91%
      versus 90%, respectively) (p<0.05). The subgroup in which DW-MRI examinations
      were performed with a 3.0 Tesla (T) device had higher pooled specificity (0.91,
      95%CI, 0.88-0.95) than the subgroup of DW-MRI with 1.5 T device (0.81, 95%CI,
      0.67, 0.94) (p<0.05). Average lesion size (<= 1.5 cm versus >1.5cm) did not
      influence the diagnostic accuracy of the test (p>0.05). CONCLUSION: Our results
      demonstrate DW-MRI has good diagnostic performance in the overall evaluation of
      hepatic metastases and equivalent to CE-MRI. Combination of CE-MRI and DW-MRI can
      improve the diagnostic accuracy of magnetic resonance (MR) imaging. Our study
      further confirms that DW-MRI can accurately detect hepatic metastases regardless
      of the lesion size. It is suggested to perform DW-MRI by 3.0 T devices, which
      might have high specificity to identify liver metastases.

PMID- 23000073
TI  - Making sense of information in noisy networks: human communication, gossip, and
      distortion.
AB  - Information from others can be unreliable. Humans nevertheless act on such
      information, including gossip, to make various social calculations, thus raising
      the question of whether individuals can sort through social information to
      identify what is, in fact, true. Inspired by empirical literature on people's
      decision-making when considering gossip, we built an agent-based simulation model
      to examine how well simple decision rules could make sense of information as it
      propagated through a network. Our simulations revealed that a minimalistic
      decision-rule 'Bit-wise mode' - which compared information from multiple sources
      and then sought a consensus majority for each component bit within the message -
      was consistently the most successful at converging upon the truth. This decision
      rule attained high relative fitness even in maximally noisy networks, composed
      entirely of nodes that distorted the message. The rule was also superior to other
      decision rules regardless of its frequency in the population. Simulations carried
      out with variable agent memory constraints, different numbers of observers who
      initiated information propagation, and a variety of network types suggested that
      the single most important factor in making sense of information was the number of
      independent sources that agents could consult. Broadly, our model suggests that
      despite the distortion information is subject to in the real world, it is
      nevertheless possible to make sense of it based on simple Darwinian computations
      that integrate multiple sources.

PMID- 23000074
TI  - Identifying if VISSIM simulation model and SSAM provide reasonable estimates for
      field measured traffic conflicts at signalized intersections.
AB  - The primary objective of this study was to identify if the VISSIM simulation
      model and the Surrogate Safety Assessment Model (SSAM) approach provided
      reasonable estimates for the traffic conflicts measured at signalized
      intersections. A total of 80h of traffic data and traffic conflicts data were
      collected at ten signalized intersections. Simulated conflicts generated by the
      VISSIM simulation model and identified by SSAM were compared to the traffic
      conflicts measured in the field. Of particular interest was to identify if the
      consistency between the simulated and the observed conflicts could be improved by
      calibrating VISSIM simulation models and adjusting threshold values used for
      defining simulated conflicts in SSAM. A two-stage procedure was proposed in this
      study to calibrate and validate the VISSIM simulation models. It was found that
      the two-stage calibration procedure improved the goodness-of-fit between the
      simulated conflicts and the real-world conflicts. Linear regression models were
      developed to study the relationship between the simulated conflicts and the
      observed conflicts. Results of data analysis showed that there was a reasonable
      goodness-of-fit between the simulated and the observed rear-end and total
      conflicts. However, it was also found that the simulated conflicts were not good
      indicators for the traffic conflicts generated by unexpected driving maneuvers
      such as illegal lane-changes in the real world. The research team further tested
      the prediction performance of the conflict prediction models using the simulated
      conflicts as independent variables. It was found that the conflict prediction
      models provided acceptable prediction performance for the total and the rear-end
      conflicts with a MAPE value of 18% and 20%, respectively. However, the prediction
      performance of the conflict prediction models for the crossing and the lane
      change conflicts was only moderate with a MAPE value of 31% and 38%,
      respectively.

PMID- 23000075
TI  - In vivo evaluation of antimyotonic efficacy of beta-adrenergic drugs in a rat
      model of myotonia.
AB  - The sodium channel blocker mexiletine is considered the first-line drug in
      myotonic syndromes, a group of muscle disorders characterized by membrane over
      excitability. We previously showed that the beta-adrenoceptor modulators,
      clenbuterol and propranolol, block voltage-gated sodium channels in a manner
      reminiscent to mexiletine, whereas salbutamol and nadolol do not. We now
      developed a pharmacological rat model of myotonia congenita to perform in vivo
      preclinical test of antimyotonic drugs. Myotonia was induced by i.p. injection of
      30 mg/kg of anthracene-9-carboxylic acid (9-AC), a muscle chloride channel
      blocker, and evaluated by measuring the time of righting reflex (TRR). The TRR
      was prolonged from <0.5 s in control conditions to a maximum of ~4 s, thirty
      minutes after 9-AC injection, then gradually recovered in a few hours. Oral
      administration of mexiletine twenty minutes after 9-AC injection significantly
      hampered the TRR prolongation, with an half-maximum efficient dose (ED(50)) of 12
      mg/kg. Both propranolol and clenbuterol produced a dose-dependent antimyotonic
      effect similar to mexiletine, with ED(50) values close to 20 mg/kg. Antimyotonic
      effects of 40 mg/kg mexiletine and propranolol lasted for 2 h. We also
      demonstrated, using patch-clamp methods, that both propranolol enantiomers
      exerted a similar block of skeletal muscle hNav1.4 channels expressed in HEK293
      cells. The two enantiomers (15 mg/kg) also showed a similar antimyotonic activity
      in vivo in the myotonic rat. Among the drugs tested, the R(+)-enantiomer of
      propranolol may merit further investigation in humans, because it exerts
      antimyotonic effect in the rat model, while lacking of significant activity on
      the beta-adrenergic pathway. This study provides a new and useful in vivo
      preclinical model of myotonia congenita in order to individuate the most
      promising antimyotonic drugs to be tested in humans.

PMID- 23000077
TI  - Respiratory chain complex II as general sensor for apoptosis.
AB  - I review here the evidence that complex II of the respiratory chain (RC)
      constitutes a general sensor for apoptosis induction. This concept emerged from
      work on neurodegenerative diseases and from recent data on metabolic alterations
      in cancer cells affecting the RC and in particular on mutations of complex II
      subunits. It is also supported by experiments with many anticancer compounds that
      compared the apoptosis sensitivities of complex II-deficient versus WT cells.
      These results are explained by the mechanistic understanding of how complex II
      mediates the diverse range of apoptosis signals. This protein aggregate is
      specifically activated for apoptosis by pH change as a common and early feature
      of dying cells. This leads to the dissociation of its SDHA and SDHB subunits from
      the remaining membrane-anchored subunits and the consequent block of it enzymatic
      SQR activity, while its SDH activity, which is contained in the SDHA/SDHB
      subcomplex, remains intact. The uncontrolled SDH activity then generates
      excessive amounts of reactive oxygen species for the demise of the cell. Future
      studies on these mitochondrial processes will help refine this model, unravel the
      contribution of mutations in complex II subunits as the cause of degenerative
      neurological diseases and tumorigenesis, and aid in discovering novel
      interference options. This article is part of a Special Issue entitled:
      Respiratory complex II: Role in cellular physiology and disease.

PMID- 23000076
TI  - Cannabinoid CB1 receptor in the modulation of stress coping behavior in mice: the
      role of serotonin and different forebrain neuronal subpopulations.
AB  - The endocannabinoid system (ECS) may either enhance or inhibit responses to
      aversive stimuli, possibly caused by its modulatory activity on diverse
      neurotransmitters. The aim of this work was to investigate the involvement of
      serotonin (5-HT) and catecholamines, as well as the role of glutamatergic and
      GABAergic cannabinoid type 1 (CB(1)) receptor, in responses to the antidepressant
      like doses of the CB(1) receptor agonist Delta(9)-tetrahydrocannabinol (THC) and
      the antagonist rimonabant in the forced swim test (FST). Mice received acute
      injections of low doses of THC (0.1 or 0.5 mg/kg) or high dose of rimonabant (3
      or 10 mg/kg) after treatment with the 5-HT synthesis inhibitor pCPA (100 mg/kg, 4
      days), the 5-HT(1A) receptor antagonist WAY100635 (1 mg/kg, acute) or the non
      selective blocker of catecholamine synthesis, AMPT (20 mg/kg, acute). THC and
      rimonabant were also tested in mutant mice lacking CB(1) receptor in specific
      forebrain neuronal subpopulations. Both THC and rimonabant induced antidepressant
      like effects, quantified as immobility in the FST. However, only THC effects were
      reversed by pCPA or WAY100635. In contrast, only AMPT could attenuate the
      rimonabant effect. We also found decreased immobility in mice lacking the CB(1)
      receptor in glutamatergic cortical neurons, but not in forebrain GABAergic
      neurons, as compared with wild-type controls. The effect of THC persisted in
      mutant mice with CB(1) receptor inactivation in GABAergic neurons, whereas
      rimonabant effects were alleviated in these mutants. Thus, employing both
      pharmacological and genetic tools, we could show that the ECS regulates stress
      responses by influencing GABAergic, glutamatergic and monoaminergic transmission.
      The antidepressant-like action of THC depends on serotonergic neurotransmission,
      whereas rimonabant effects are mediated by CB(1) receptor on GABAergic neurons
      and by catecholamine signaling.

PMID- 23000078
TI  - The role of the PsbS protein in the protection of photosystems I and II against
      high light in Arabidopsis thaliana.
AB  - The PsbS protein is recognised in higher plants as an important component in
      dissipating excess light energy via its regulation of non-photochemical
      quenching. We investigated photosynthetic responses in the arabidopsis npq4
      mutant, which lacks PsbS, and in a mutant over-expressing PsbS (oePsbS). Growth
      under low light led to npq4 and wild-type plants being visibly indistinguishable,
      but induced a phenotype in oePsbS plants, which were smaller and had shorter
      flowering spikes. Here we report that chloroplasts from npq4 generated more
      singlet oxygen ((1)O(2)) than those from oePsbS. This accompanied a higher extent
      of photosystem II photoinhibition of leaves from npq4 plants. In contrast, oePsbS
      was more damaged by high light than npq4 and the wild-type at the level of
      photosystem I. The plastoquinone pool, as measured by thermoluminescence, was
      more oxidised in the oePsbS than in npq4, whilst the amount of photo-oxidisable
      P(700), as probed with actinic light or saturating flashes, was higher in oePsbS
      compared to wild-type and npq4. Taken together, this indicates that the level of
      PsbS has a regulatory role in cyclic electron flow. Overall, we show that under
      high light oePsbS plants were more protected from (1)O(2) at the level of
      photosystem II, whereas lack of cyclic electron flow rendered them susceptible to
      damage at photosystem I. Cyclic electron flow is concluded to be essential for
      protecting photosystem I from high light stress.

PMID- 23000079
TI  - Egyptian horned viper Cerastes cerastes venom hyaluronidase: purification,
      partial characterization and evidence for its action as a spreading factor.
AB  - Novel Hyaluronidase CcHaseII (33 kDa) of the most dangerous horned viper Cerastes
      cerastes (Cc) was purified and partial characterized in a set of biochemical
      assays. CcHaseII was purified by applying a protocol of two successive
      chromatographic steps; gel filtration on a Sephacryl S-200 and cation exchange
      chromatography on CM-Sepharose columns. It has specific activity 4000 units/mg
      protein against 154 units/mg protein for the whole venom with 26-purification
      fold. The enzymatic activity of the purified Hyaluronidase stimulated by Na(+)
      and inhibited by entire tested cations, metalloproteinase inhibitors and heparin.
      CcHaseII (5-10 MUg) enhanced one hundred percent of hemorrhagic activity of the
      potent purified hemorrhagic SVMP of corresponding venom (CcHTI) and enhanced
      edema-inducing activity of Cc venom in a dose-dependent manner. Furthermore, the
      described purification procedure allows simple preparation of appreciable
      quantities of the CcHaseII for further studies. Eventually, exploration of snake
      venom antigenic parts is the most crucial factor for establishing good immunogens
      and specific diagnostic reagents.

PMID- 23000081
TI  - Integrating comparative effectiveness design elements and endpoints into a phase
      III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided
      management for women with breast cancer involving lymph nodes.
AB  - Women with breast cancer involving the lymph nodes are typically treated with
      cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that
      the 21-gene test (OncotypeDX(r)), may allow identification of those who can
      safely avoid chemotherapy. To better understand the performance of the 21-gene
      test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer)
      study was designed, a multicenter Phase III trial randomizing women with hormone
      receptor-positive and HER2-negative breast cancer involving 1-3 lymph nodes and a
      21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone
      versus chemotherapy followed by endocrine therapy. As one of the first large
      scale comparative-effectiveness studies in oncology, RxPONDER utilized an
      external stakeholder group to help inform the design of the trial. Stakeholders
      met with representatives of SWOG over several months through a structured
      discussion process. The stakeholder engagement process resulted in several
      changes being made to the trial design. In addition, stakeholder representatives
      from the health insurance industry provided guidance regarding a mechanism
      whereby the costs of OncotypeDX(r) would be paid by the majority of health
      insurers as part of the trial. The process may serve as a template for future
      studies evaluating the comparative effectiveness of genomic tests in oncology,
      particularly those that are conducted within cooperative clinical trials groups.

PMID- 23000082
TI  - Improvement of a puromycin-linker to extend the selection target varieties in
      cDNA display method.
AB  - cDNA display using a puromycin-linker to covalently bridge a protein and its
      coding cDNA is a stable and efficient in vitro protein selection method. The
      optimal design of the often-used puromycin-linker is vital for effective
      selection. In this report, an improved puromycin-linker containing deoxyinosine
      bases as cleavage sites, which are recognized by endonuclease V, was introduced
      to extend the variety of the selection targets to molecules such as RNA. The
      introduction of this linker enables efficient in vitro protein selection without
      contamination from RNase T1, which is used for the conventional linker containing
      ribonucleotide G bases. In addition, mRNA-protein fusion efficiency was found to
      not depend on the length of the flexible poly (ethylene glycol) (PEG) region of
      the linker. These findings will allow practical and easy-to-use in vitro protein
      selection by cDNA display.

PMID- 23000080
TI  - Can lifestyle modification improve neurocognition? Rationale and design of the
      ENLIGHTEN clinical trial.
AB  - BACKGROUND: Risk factors for cardiovascular disease (CVD) not only increase the
      risk for clinical CVD events, but also are associated with a cascade of
      neurophysiologic and neuroanatomic changes that increase the risk of cognitive
      impairment and dementia. Although epidemiological studies have shown that
      exercise and diet are associated with lower CVD risk and reduced incidence of
      dementia, no randomized controlled trial (RCT) has examined the independent
      effects of exercise and diet on neurocognitive function among individuals at risk
      for dementia. The ENLIGHTEN trial is a RCT of patients with CVD risk factors who
      also are characterized by subjective cognitive complaints and objective evidence
      of neurocognitive impairment without dementia (CIND) STUDY DESIGN: A 2 by 2
      design will examine the independent and combined effects of diet and exercise on
      neurocognition. 160 participants diagnosed with CIND will be randomly assigned to
      6 months of aerobic exercise, the DASH diet, or a combination of both exercise
      and diet; a (control) group will receive health education but otherwise will
      maintain their usual dietary and activity habits. Participants will complete
      comprehensive assessments of neurocognitive functioning along with biomarkers of
      CVD risk including measures of blood pressure, glucose, endothelial function, and
      arterial stiffness. CONCLUSION: The ENLIGHTEN trial will (a) evaluate the
      effectiveness of aerobic exercise and the DASH diet in improving neurocognitive
      functioning in CIND patients with CVD risk factors; (b) examine possible
      mechanisms by which exercise and diet improve neurocognition; and (c) consider
      potential moderators of treatment, including subclinical CVD.

PMID- 23000083
TI  - History of endometriosis may adversely affect the outcome in menopausal
      recipients of sibling oocytes.
AB  - Due to the known adverse effect of endometriosis on gamete quality, it has always
      been difficult to demonstrate a direct effect of endometriosis on implantation.
      In order to eliminate these confounding effects, this prospective comparative
      study studied a population of menopausal recipients with and without
      endometriosis sharing sibling oocytes coming from the same donor. The aim was to
      understand the impact of endometriosis on implantation, pregnancy and live birth
      rates in menopausal recipients. A total of 240 menopausal recipients of donated
      sibling oocytes, were divided in two groups. Group I consisted of 120 recipients
      diagnosed with endometriosis and group II consisted of 120 controls. The
      implantation and pregnancy rates were significantly lower in the endometriosis
      group compared with the control group (23.81% versus 31.48%, P=0.019; 45.00%
      versus 58.33%, P=0.039, respectively). In oocyte donation cycles, a recipient's
      history of endometriosis might have a negative impact on implantation, pregnancy
      and live birth rates, even in menopausal women. Infertility in endometriosis may
      be due to poor oocyte quality or embryos with decreased ability to implant due to
      impaired fertilization. There are no conclusive data on the impact of
      endometriosis on implantation. The already-known adverse effect of endometriosis
      on gamete quality makes it more difficult to demonstrate a direct effect of
      endometriosis on implantation. In order to eliminate these confounding effects we
      studied a population of menopausal recipients with and without endometriosis
      sharing sibling oocytes coming from the same oocyte donor. The oocyte donation
      model was used in an attempt to understand whether the endometrium, the oocytes
      or both are affected by endometriosis. The aim of the present study was to
      understand the impact of endometriosis on implantation, pregnancy and live birth
      rates in menopausal recipients. A total of 240 menopausal recipients of donated
      sibling oocytes were divided into two groups. Group I consisted of 120 recipients
      diagnosed with endometriosis and group II consisted of 120 controls. The
      pregnancy and implantation rates were significantly lower in the endometriosis
      group compared to the control group (45.00% versus 58.33%, P=0.039) and (23.81%
      versus 31.48%, P=0.019) respectively. In oocyte donation cycles, a recipient's
      history of endometriosis might have a negative impact on implantation, pregnancy
      and live birth rates, even in menopausal women.

PMID- 23000084
TI  - Circulating trophoblastic cells provide genetic diagnosis in 63 fetuses at risk
      for cystic fibrosis or spinal muscular atrophy.
AB  - This study sought to determine whether a reliable non-invasive prenatal diagnosis
      (NI-PND) of cystic fibrosis (CF) or spinal muscular atrophy (SMA) can be achieved
      through analysis of circulating fetal trophoblastic cells (CFTC). The kinetics of
      CFTC circulation were also studied. CFTC were isolated by isolation by size of
      epithelial tumour/trophoblastic cells at 9-11 weeks of gestation, before
      chorionic villus sampling (CVS), from the blood of 63 pregnant women at 25% risk
      for having a child affected by either CF (n=32) or SMA (n=31). Collected cells
      were laser-microdissected, short tandem repeat-genotyped to determine fetal
      origin and blindly assessed for mutation analysis. CFTC were independently
      analysed weekly (4-12 weeks of gestation) in 14 women who achieved pregnancy
      following IVF. Diagnostic results were compared with those obtained by CVS. All
      seven CF and seven SMA pregnancies carrying an affected fetus were correctly
      identified as well as non-affected pregnancies. CFTC provided 100% diagnostic
      sensitivity (95% CI 76.8-100%) and specificity (95% CI 92.7-100%) in these 63
      consecutive pregnancies at risk for CF or SMA. CFTC were found to circulate from
      5 weeks of gestation and can be used to develop an early and reliable approach
      for NI-PND. We sought to determine whether a reliable non-invasive prenatal
      diagnosis (NI-PND) of two rare genetic diseases - cystic fibrosis (CF) and spinal
      muscular atrophy (SMA) - can be achieved through analysis of circulating fetal
      trophoblastic cells (CFTC) in blood of pregnant women. We also studied the time
      of appearance and circulation of CFTC in maternal blood. CFTC were isolated from
      maternal blood by isolation by size of epithelial tumour/trophoblastic cells
      (ISET; an approach for cell isolation from blood) at 9-11 weeks of gestation
      before chorionic villus sampling (CVS) from the blood of 63 pregnant women at 25%
      risk for having a child affected by either CF (n=32) or SMA (n=31). Collected
      cells were analysed by genetic test to determine fetal origin and blindly
      assessed for mutation analysis. We independently analysed CFTC in maternal blood
      samples taken weekly (4-12 weeks of gestation) from 14 women who achieved
      pregnancy following IVF. Diagnostic results were compared with those obtained by
      CVS. All seven CF and seven SMA pregnancies carrying an affected fetus were
      correctly identified as well as non-affected pregnancies. CFTC provided 100%
      diagnostic sensitivity and specificity in these 63 consecutive pregnancies at
      risk for CF or SMA. CFTC were found to circulate from 5 weeks of gestation and
      can be used to develop an early and reliable approach for NI-PND.

PMID- 23000085
TI  - Long anterior mandibular tooth roots in Neanderthals are not the result of their
      large jaws.
AB  - Tooth root length has been shown to taxonomically distinguish Neanderthals from
      modern humans. However, this may result from differences in jaw size between both
      taxa, although most previous studies have revealed a very low or non-existent
      correlation between tooth size and jaw size in recent modern humans. We therefore
      investigated, within a broader taxonomical frame, to what extent measurements on
      the anterior tooth roots and the symphyseal region covary. Our samples comprise
      permanent mandibular incisors and canines from Mauer, Neanderthals, and extant
      and fossil modern humans sensu lato. Using micro-computed tomography, we took
      linear and cross-sectional surface area measurements of the roots and the
      symphyseal region and calculated the root volume. We also measured 3D landmarks
      to quantify the overall size of the mandible using centroid size. Furthermore, we
      analyzed the relationship between root size and symphyseal shape, based on
      Procrustes shape variables of semi-landmarks along the symphyseal outline. Our
      results show that Neanderthals have significantly larger anterior tooth roots
      than recent modern humans in terms of root length, mid-sagittal surface area and
      volume, even after correction for mandibular size. In contrast, symphyseal height
      and width do not differ significantly between both taxa, whereas, without
      scaling, the mid-sagittal symphyseal surface area and the centroid size of the
      mandible do differ. Importantly, no significant correlation was found between any
      of the root and symphyseal measurements after correction for overall mandibular
      size. The shape analyses revealed that Neanderthals have a vertical symphyseal
      profile with an evenly-thick symphysis, whereas recent modern humans display an
      unevenly-thick symphysis, comprising a pronounced incurvatio mandibularis and a
      bony chin. These results suggest a negative evolutionary allometry for the recent
      modern human anterior root size. Therefore, root length and other root dimensions
      can be considered taxonomically relevant for distinguishing Neanderthals from
      modern humans.

PMID- 23000086
TI  - Interferon-alpha in combination with sorafenib: RAPSODY or requiem?

PMID- 23000087
TI  - CXCL8, an underestimated "bad guy" in prostate cancer.

PMID- 23000088
TI  - A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium
      chloride (Ra 223) in patients with bone metastases and castration-resistant
      prostate cancer.
AB  - BACKGROUND: Patients with castration-resistant prostate cancer (CRPC) and bone
      metastases have an unmet clinical need for effective treatments that improve
      quality of life and survival with a favorable safety profile. OBJECTIVE: To
      prospectively evaluate the efficacy and safety of three different doses of radium
      chloride (Ra 223) in patients with CRPC and bone metastases. DESIGN, SETTING, AND
      PARTICIPANTS: In this phase 2 double-blind multicenter study, 122 patients were
      randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of
      25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the
      proportion of patients in each dose group who had a confirmed decrease of >= 50%
      in baseline prostate-specific antigen (PSA) levels. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Efficacy was evaluated using blood samples to measure PSA
      and other tumor markers, recorded skeletal-related events, and pain assessments.
      Safety was evaluated using adverse events (AEs), physical examination, and
      clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between
      groups. RESULTS AND LIMITATIONS: The study met its primary end point with a
      statistically significant dose-response relationship in confirmed >= 50% PSA
      declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in
      the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group
      (p=0.0297). A >= 50% decrease in bone alkaline phosphatase levels was identified
      in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-,
      and 80-kBq/kg dose groups, respectively (p<0.0001). The most common treatment
      related AEs (>= 10%) occurring up to week 24 across all dose groups were diarrhea
      (21%), nausea (16%), and anemia (14%). No difference in incidence of hematologic
      events was seen among dose groups. Potential limitations include small patient
      numbers and differences among dose groups at baseline. CONCLUSIONS: Ra 223 had a
      dose-dependent effect on serum markers of CRPC activity, suggesting that control
      of bone disease with Ra 223 may affect cancer-related outcomes. Ra 223 was well
      tolerated at all doses. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00337155.

PMID- 23000089
TI  - A comparison of the full Mini Nutritional Assessment, short-form Mini Nutritional
      Assessment, and Subjective Global Assessment to predict the risk of protein
      energy malnutrition in patients on peritoneal dialysis: a cross-sectional study.
AB  - BACKGROUND: The full Mini Nutritional Assessment (full-MNA) and short-form MNA
      (MNA-SF) are simple and effective nutrition screening scales, but their
      usefulness for identifying patients with peritoneal dialysis (PD) at risk of
      protein-calorie malnutrition (PEM) has not been investigated. OBJECTIVES: This
      study was aimed to investigate the convergent validity of the full-MNA and MNA-SF
      for identifying patients with PD at risk of PEM. DESIGN: A cross-sectional study.
      SETTING: A hospital-managed dialysis center. PARTICIPANTS: 80 adult ambulatory PD
      patients. METHODS: Patients were interviewed for personal data and rated with the
      full-MNA, MNA-SF and the Subjective Global Assessment (SGA) for nutritional
      status. The consistency among the scales was assessed with kappa coefficients.
      The ability of each scale to differentiate undernutrition was evaluated with
      external standards including serum albumin and creatinine concentrations, mid-arm
      and calf circumferences, and dialysis-related indicators. Statistical
      significance was evaluated with Wilcoxon rank-sum test. RESULTS: The full-MNA and
      MNA-SF showed low agreements with the SGA (kappa=0.346 and 0.185, respectively).
      The full-MNA and MNA-SF performed better than the SGA in differentiating
      undernutrition according to the external standards. However, contrary to general
      expectation, MNA-SF rated a significantly smaller proportion of subjects at risk
      of undernutrition. CONCLUSION: The full-MNA and MNA-SF are more able than the SGA
      in identifying PD patients at risk of PEM. However, MNA-SF rates a smaller
      proportion of PD patients at risk of undernutrition than the full-MNA. The use of
      MNA-SF as a stand-alone unit requires further confirmation.

PMID- 23000090
TI  - Therapeutic patient education for stroke survivors: Non-pharmacological
      management. A literature review.
AB  - OBJECTIVES: Focus on the different therapeutic patient education (TPE) programs
      for stroke survivors found in the literature. Verify their content and efficacy.
      METHOD: A literature review was conducted by searching for entries from 1966 to
      2011 in the Medline and Cochrane Library databases. The references for the
      accepted articles were taken into consideration and the articles corresponding to
      the criteria inclusion but not present within the initial search were selected.
      The keywords used were "self care", "self management", "patient education" and
      "stroke". Given the multiplicity of symptoms that may be addressed in TPE
      programs, and following expert advice, the symptoms were grouped after expanding
      the bibliographic search using the following, additional keywords: "dysphagia";
      "swallowing disorder"; "urinary incontinence"; "caregiver"; "fall prevention";
      "falling"; "injury"; "shoulder pain"; "physical activity"; "exercise"; "aphasia"
      and "cognitive impairment". RESULTS: We found 30 article abstracts. In the end,
      we only accepted seven articles on general TPE programs that were well structured
      and detailed enough. The TPE programs found in the literature were often of
      questionable methodological quality. The multiplicity of symptoms led to very
      general TPE programs that covered all possible stroke after-effects. The purpose
      of these programs was to reduce stress and anxiety, to improve quality of life
      and to alleviate psychosocial after-effects. A change in caregiver and patient
      behavior was observed at times. We expanded the bibliographic search to include
      scientific arguments that could help implement TPE programs for more specific
      targets. CONCLUSION: TPE programs for stroke survivors could be improved by
      standardizing and assessing programs that focus on a specific problem caused by
      the various possible after-effects of strokes. In order to promote education for
      stroke survivors, specific training for health care professionals and appropriate
      funding are necessary.

PMID- 23000091
TI  - Phage-antibiotic synergism: a possible approach to combatting Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is a highly resistant opportunistic pathogen and an
      important etiological agent of various types of infections. During the last
      decade, P. aeruginosa phages have been extensively examined as alternative
      antimicrobial agents. The aim of the study was to determine antimicrobial
      effectiveness of combining subinhibitory concentrations of gentamicin,
      ceftriaxone, ciprofloxacin or polymyxin B with P. aeruginosa-specific
      bacteriophages belonging to families Podoviridae and Siphoviridae. The time-kill
      curve method showed that a combination of bacteriophages and subinhibitory
      concentrations of ceftriaxone generally reduced bacterial growth, and synergism
      was proven for a Siphoviridae phage sigma-1 after 300 min of incubation. The
      detected alteration in morphology after ceftriaxone application, resulting in
      cell elongation, along with its specific mode of action, seemed to be a necessary
      but was not a sufficient reason for phage-antibiotic synergism. The phenomenon
      offers an opportunity for future development of treatment strategies for
      potentially lethal infections caused by P. aeruginosa.

PMID- 23000092
TI  - Accumulation capacity of primary cultures of adipocytes for PCB-126: influence of
      cell differentiation stage and triglyceride levels.
AB  - Polychlorinated biphenyls (PCBs) are lipophilic persistent organic chemicals that
      accumulate at high concentrations in the adipose tissue. Recent studies correlate
      the presence of such contaminants in fat cells to possible alterations in the
      regulation of energy homeostasis in adipocytes. As the adipose tissue is composed
      of adipocytes at several stages of differentiation, it is possible that PCBs
      already accumulate in cells at an early stage, and thereby impair their
      development. The exact driving force enabling the massive accumulation of PCBs in
      fat cells remains unclear. The present study investigated the time-course
      incorporation of (3)H-PCB-126 in primary cultures of rat adipocytes at both early
      and late differentiation stages and showed that the accumulation of this congener
      was already significant at an early stage of differentiation. In addition,
      triglyceride levels in cells were an important parameter governing (3)H-PCB-126's
      entry. The extent of adipocyte ability to store this pollutant in vitro was also
      evaluated and revealed that fat cells were able to accumulate (3)H-PCB-126 at
      extremely high concentrations. A linear relationship was observed between the
      amount of (3)H-PCB-126 added to the medium and the one accumulated in the cells,
      which favors a passive diffusion mechanism for the entry of this pollutant into
      fat cells.

PMID- 23000093
TI  - Marine sponge steroids as nuclear receptor ligands.
AB  - Nuclear receptors (NRs) are a large family of evolutionarily conserved and ligand
      regulated transcription factors. The farnesoid X receptor (FXR) and the pregnane
      X receptor (PXR) are two bile-acid-activated receptors highly expressed in
      enterohepatic tissues essential for bile acids and xenobiotic metabolism. More
      than 1600 new steroidal structures have been isolated from marine organisms.
      Chemical, structural, and pharmacological characterization of sponge steroid
      libraries has allowed the identification of steroids that regulate FXR and PXR:
      selective FXR antagonists, FXR modulators, FXR antagonists endowed with PXR
      agonism, and selective PXR agonists. Selective FXR antagonists (theonellasterol)
      have proven effective in protecting against liver injury in models of
      cholestasis. Selective PXR agonists (natural and synthetic solomonsterols) have
      been effective in reducing nuclear factor (NF)-kappaB activity and intestinal
      inflammation. Identification of marine steroids endowed with dual FXR and PXR
      agonism-antagonism probably reflects the common identity of the unique ancestral
      precursor of these NRs. These findings pave the way to the development of novel
      FXR and PXR agonists and antagonists to target human diseases.

PMID- 23000094
TI  - Ghrelin protects against cobalt chloride-induced hypoxic injury in cardiac H9c2
      cells by inhibiting oxidative stress and inducing autophagy.
AB  - Ghrelin is a multifunctional peptide that actively protects against
      cardiovascular ischemic diseases, but the underlying mechanisms are unclear. We
      used CoCl(2) to mimic hypoxic conditions in cardiac H9c2 cells in order to study
      the mechanism by which ghrelin protects cardiac myocytes against hypoxic injury
      by regulating the content of intracellular ROS and autophagy levels. Cell
      apoptosis and necrosis were evaluated by the flow cytometry assay, Hoechst
      staining, and LDH activity. Cell viability was detected by the WST-1 assay; ROS
      levels were assessed using DCFH2-DA; and Nox1, catalase and Mn-SOD were assayed
      by real-time PCR and activity assays. LC3II was measured by Western blot
      analysis. We observed that CoCl(2) induced apoptosis and death of H9c2 cells in a
      dose- and time-dependent manner. This was characterized by an increase in cell
      apoptosis, LDH activity, ROS content, Nox1 expression, and autophagy levels and a
      decrease in cell viability, catalase, and Mn-SOD activities. Ghrelin treatment
      significantly attenuated CoCl(2)-induced hypoxic injury by decreasing cell
      apoptosis, LDH activity, ROS content, and Nox1 expression and increasing cell
      viability, autophagy levels, catalase, and Mn-SOD mRNA levels and activities.
      Further experiments revealed that inhibiting autophagy using 3-MA or AMPK pathway
      with compound C almost abrogated the induction of ghrelin in autophagy. This was
      associated with a decrease in cell viability and an increase in LDH activity. Our
      results indicate that ghrelin protected cardiac myocytes against CoCl(2)-induced
      hypoxic injury by decreasing Nox1 expression, increasing the expression and
      activity of endogenous antioxidant enzymes, and inducing protective autophagy in
      an AMPK-dependent manner.

PMID- 23000095
TI  - A novel class of antimicrobial peptides from the scorpion Heterometrus spinifer.
AB  - The venom peptides from the scorpion Heterometrus spinifer have been poorly
      characterized so far. Here, we identified a novel class of antimicrobial peptides
      from the venom gland of H. spinifer, which were referred to as HsAp, HsAp2, HsAp3
      and HsAp4, respectively. Each of the four peptides consists of 29 amino acid
      residues, and is cationic and weakly amphipathic. They display no significant
      homology to any other known peptides, and thus represent a new family of venom
      peptides from scorpions. Antimicrobial assay showed that HsAp is able to inhibit
      the growth of both Gram-negative and Gram-positive bacteria with the MIC values
      of 11.8-51.2 MUM. HsAp is also able to inhibit the growth of the tested fungus.
      Genomic analysis indicated that the genes of all the four peptides are
      intronless. Our studies expand the families of antimicrobial peptides from
      scorpions.

PMID- 23000097
TI  - Polymorphisms of catechol estrogens metabolism pathway genes and breast cancer
      risk in Mexican women.
AB  - Breast cancer is associated to estrogen exposure. Allelic variants involved in
      estrogen metabolism might change the risk of developing this neoplasia. We
      examined the potential association of breast cancer risk in Mexican women with
      the polymorphisms CYP1A1 rs1048943, CYP1B1 rs1056836, COMT rs4680, GSTP1 rs1695,
      GSTT1 null and GSTM1 null which are involved in estrogen metabolism pathway. This
      study included 150 cases and 150 controls. A significant association was observed
      between, CYP1A1 rs1048943 (OR = 1.95, C.I. 1.13-3.36) and GSTP1 rs1695 (OR =
      2.39, C.I. 1.24-4.24) polymorphisms with the risk of breast cancer. This risk was
      increased when the women were stratified according to their menopausal status.
      The results show that breast cancer risk significantly increases in women with 3
      6 risk polymorphisms (OR = 3.75, C.I. 1.44-9.74).

PMID- 23000098
TI  - Preventive effects of rutin on the development of experimental diabetic
      nephropathy in rats.
AB  - AIMS: Diabetic nephropathy (DN) is an important microvascular complication and
      one of the main causes of end-stage renal disease. In this study, the preventive
      effect and mechanism of rutin on the development of DN in streptozotocin (STZ)
      induced diabetic rats were investigated. MAIN METHODS: After an early DN model
      was induced by STZ, rats were orally administered rutin at 3 doses for 10 weeks.
      Fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), urine protein,
      kidney index, antioxidase, advanced glycosylation end products (AGEs),
      extracellular matrix (ECM) including collagen IV and laminin, connective tissue
      growth factor (CTGF), phosphorylated Smad 2/3 (p-Smad 2/3) and Smad 7 (p-Smad 7),
      and transforming growth factor-beta(1) (TGF-beta(1)) were determined by different
      methods, respectively. The ultrastructural morphology was observed by a
      transmission electron microscope. KEY FINDINGS: Compared with the DN group, rutin
      decreased the levels of fasting blood glucose, Cr, BUN, urine protein, the
      intensity of oxidative stress and p-Smad 7 significantly. The expression of AGEs,
      collagen IV and laminin, TGF-beta(1), p-Smad 2/3 and CTGF was inhibited by rutin
      significantly. Moreover, rutin was observed to inhibit proliferation of mesangial
      cells and decrease thickness of glomerular basement membrane (GBM) by electron
      microscopy. SIGNIFICANCE: The preventive effect of rutin on the development of DN
      is closely related to oxidative stress and the TGF-beta(1)/Smad/ECM and TGF
      beta(1)/CTGF/ECM signaling pathways. Those results suggest that rutin can prevent
      the development of experimental DN in rats.

PMID- 23000099
TI  - Prenatal exposure to methanol as a dopamine system sensitization model in
      C57BL/6J mice.
AB  - AIMS: In this study, the effects of prenatal exposure to methanol (MeOH) on the
      nigrostriatal dopamine (NSDA) system were examined to determine if the
      interaction could sensitize this system, and serve as an underpinning for
      Parkinson's disease (PD) like changes that occur later in life. Methanol was
      studied because its toxicity resembles the symptoms of PD and the symptoms are
      relieved by L-dopa meaning that MeOH targets the NSDA system. Since fermentation
      and wood combustion are major sources for MeOH, the incidence of human encounters
      with MeOH is high. As a superior solvent and the precursor for formaldehyde, MeOH
      has a powerful and sometimes, irreversible impact on chemical processes, such as
      cross-linking proteins and nucleic acids. It may cause subthreshold changes that
      sensitizes the NSDA system to PD, that occur during aging. MAIN METHODS: To study
      the prenatal effects of MeOH, pregnant C57BL/6J mice were administered 40 mg/kg
      MeOH by oral gavage during gestation days 8-12, twice daily. Twelve weeks after
      birth, behavior impairments were recorded. The striatum was dissected for the
      determination of tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase
      (LAAD), alpha-synuclein and levels of dopamine (DA) and its metabolites. KEY
      FINDINGS: MeOH reduced striatal TH and LAAD protein by 47% and 57% respectively
      and DA by 32%. SIGNIFICANCE: The results mean that in utero exposure to toxins
      similar to MeOH could sensitize the striatal system to changes that cause PD.
      This study may help identify strategies to block this type of in utero toxicity.

PMID- 23000100
TI  - A novel small molecule, NecroX-7, inhibits osteoclast differentiation by
      suppressing NF-kappaB activity and c-Fos expression.
AB  - AIMS: Osteoclasts, the unique bone-resorbing polykaryons, are responsible for
      many bone-destructive diseases, such as osteoporosis and rheumatoid arthritis.
      Hence, the regulation of osteoclast formation is considered a potential
      therapeutic approach for these diseases. In this study, we investigated the
      effect of a novel small compound, C(25)H(32)N(4)O(4)S(2) (NecroX-7) on osteoclast
      formation. MAIN METHODS: We analyzed the effects of NecoX-7 on receptor activator
      of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation in
      vitro and LPS-induced bone loss in vivo. KEY FINDINGS: We observed that NecroX-7
      suppressed osteoclast formation from primary bone marrow macrophages (BMMs) in a
      dose-dependent manner. NecroX-7 significantly inhibited the NF-kappaB signaling
      pathway without affecting the activation of the mitogen-activated protein kinases
      (MAPKs) JNK, p38, and ERK in response to RANKL. In addition, NecroX-7 strongly
      attenuated the induction of c-Fos and nuclear factor of activated T cells c1
      (NFATc1), which are crucial transcription factors for osteoclast differentiation.
      Mirroring the down-regulation of c-Fos and NFATc1, the expression of
      osteoclastogenic markers, such as tartrate-resistant acid phosphatase (TRAP) and
      cathepsin K, was also reduced by the addition of NecroX-7. Furthermore,
      confirming the in vitro anti-osteoclastogenic effect, NecroX-7 inhibited
      lipopolysaccharide (LPS)-induced bone loss in vivo. SIGNIFICANCE: Our data imply
      that NecroX-7 is useful as a therapeutic drug for the treatment of bone
      resorption-associated diseases.

PMID- 23000101
TI  - Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in
      streptozotocin-induced diabetic mice.
AB  - AIMS: Increased protein O-GlcNAcylation occurs in response to increased
      availability of glucose and fatty acids and is a hallmark of diabetes. Previous
      studies have demonstrated an improvement in heart function associated with
      decreased protein O-GlcNAcylation. Our group has recently demonstrated a capacity
      for exercise to decrease protein O-GlcNAcylation in the heart of normal mice;
      however, the impact of such training under diabetic conditions has not been
      examined. MAIN METHODS: Diabetes was induced in mice through injection of
      streptozotocin. Animals either remained sedentary or were subjected to 6 weeks of
      swim training protocol. At the end of 6 weeks in vivo cardiac function was
      assessed and the hearts were harvested for gene expression and Western blotting
      in relation to O-GlcNAcylation KEY FINDINGS: Diabetes resulted in elevated blood
      glucose relative to non-diabetic mice. Relative to the sedentary diabetic group,
      the rate of relaxation (Tau) was significantly improved in the exercised group.
      Western blot analysis revealed an increase in protein O-GlcNAcylation in the
      diabetic group which was reversed through exercise despite persistent
      hyperglycemia. No change in the expression of O-GlcNAc transferase (OGT) was
      noted between sedentary and exercised diabetic mice; however an increase in the
      expression and activity of O-GlcNAcase (OGA) was apparent in the exercised group.
      SIGNIFICANCE: This study demonstrates the potential for exercise training to
      decrease intracellular protein O-GlcNAcylation in the heart even under conditions
      of persistent hyperglycemia associated with diabetes. Our results suggest the
      beneficial effects of regular aerobic exercise extend beyond simple regulation of
      blood glucose levels.

PMID- 23000102
TI  - Comment on: sleeve gastrectomy and crural repair in obese patients with
      gastroesophageal reflux disease and/or hiatal hernia.

PMID- 23000103
TI  - Relation of cytosolic iron excess to cardiomyopathy of Friedreich's ataxia.
AB  - Cardiomyopathy is the leading cause of death in Friedreich's ataxia. This
      autosomal recessive disease is caused by a homozygous guanine-adenine-adenine
      trinucleotide repeat expansion in the frataxin gene (chromosome 9q21). One
      untoward effect of frataxin deficiency is the lack of iron (Fe)-sulfur clusters.
      Progressive remodeling of the heart in FA, however, may be more specifically
      related to sarcoplasmic Fe overload. The Fe-containing inclusions in a small
      percentage of cardiomyocytes may not represent purely mitochondrial accumulation
      of the metal. The objective of the present study was to re-examine the
      contribution of Fe to cardiomyocyte hypertrophy, fiber necrosis, and myocardial
      scarring, using a combination of X-ray fluorescence, slide histochemistry of Fe,
      and immunohistochemistry of 2 Fe-related proteins. Polyethylene glycol-embedded
      human cardiac tissues from the left and right ventricular walls, ventricular
      septum, right atrium, and atrial septum were studied using qualitative and
      quantitative X-ray fluorescence. Tissues were recovered from the polyethylene
      glycol matrix, re-embedded in paraffin, and sectioned for visualization of Fe,
      ferritin, and ferroportin. X-ray fluorescence showed quantifiable levels of Fe
      and zinc. Regions of significantly increased Fe (1 to 4 mm(2)) were irregularly
      distributed throughout the working myocardium. Fe granules were sparse in
      conductive tissue. Zinc signals remained unchanged. Robust cytosolic ferritin
      reaction product occurred in many fibers of the affected regions. Ferroportin
      displayed no response except in fibers with advanced Fe overload. These
      observations are at variance with the concept of selective Fe overload only in
      cardiac mitochondria. In conclusion, Fe-mediated damage to cardiomyocytes and
      myocardial scarring are more likely due to cytosolic Fe excess.

PMID- 23000104
TI  - Electrocardiogram in pneumonia.
AB  - Findings on electrocardiogram may hint that pulmonary embolism (PE) is present
      when interpreted in the proper context and lead to definitive imaging tests.
      However, it would be useful to know if electrocardiographic (ECG) abnormalities
      also occur in patients with pneumonia and whether these are similar to ECG
      changes with PE. The purpose of this investigation was to determine ECG findings
      in patients with pneumonia. We retrospectively evaluated 62 adults discharged
      with a diagnosis of pneumonia who had no previous cardiopulmonary disease and had
      electrocardiogram obtained during hospitalization. The most prevalent ECG
      abnormality, other than sinus tachycardia, was minor nonspecific ST-segment or T
      wave changes occurring in 13 of 62 (21%). Right atrial enlargement occurred in 4
      of 62 (6.5%). QRS abnormalities were observed in 24 of 62 (39%). Right-axis
      deviation and S(1)S(2)S(3) were the most prevalent QRS abnormalities, which
      occurred in 6 of 62 (9.7%). Complete right bundle branch block and S(1)Q(3)T(3)
      pattern occurred in 3 of 62 (4.8%). ECG abnormalities that were not present
      within 1 month previously or abnormalities that disappeared within 1 month
      included left-axis deviation, right-axis deviation, right atrial enlargement,
      right ventricular hypertrophy, S(1)S(2)S(3), S(1)Q(3)T(3), low-voltage QRS
      complexes, and nonspecific ST-segment or T-wave abnormalities. In conclusion,
      electrocardiogram in patients with pneumonia often shows QRS abnormalities or
      nonspecific ST-segment or T-wave changes. ECG findings are similar to ECG
      abnormalities in PE and electrocardiogram cannot assist in the differential
      diagnosis.

PMID- 23000105
TI  - Klotho modulates the stress response in human senescent endothelial cells.
AB  - Lack of Klotho expression in mice leads to premature aging and age-related
      diseases, including vascular diseases. The aim of this study was to determine how
      endothelial cell line senescence affects Klotho expression and whether intra- or
      extracellular Klotho has any effect on the response of senescent cells to
      oxidative stress. The study was performed using human endothelial cells (HUVEC);
      cell aging was obtained by prolongation of cell division to 42 population
      doublings (PD). Senescence was also obtained by exposure to TNFalpha, which
      causes cell changes resembling cellular senescence. The decline in Klotho
      preceded the manifestations of cell ageing: telomere shortening and beta
      galactosidase expression. Klotho was also reduced in cells exposed to the
      proinflammatory cytokine TNFalpha. The addition of exogenous Klotho to aging
      cells did not modify the proportion of cells with short telomeres or any other
      feature of cell aging; however, exogenous Klotho prevented the changes resembling
      premature cellular senescence associated with TNFalpha, such as the decrease in
      telomere length and the increase in beta-galactosidase-positive cells. Likewise
      exogenous Klotho prevented the increases in reactive oxygen species (ROS)
      activity, mitochondrial potential and cell apoptosis induced by TNFalpha.

PMID- 23000106
TI  - Behavioral and academic problems in children with Sturge-Weber syndrome:
      differences between children with and without seizures.
AB  - Although Sturge-Weber (SWS) syndrome is associated with behavioral and academic
      problems in childhood, it is unknown whether those problems are concomitants of
      the disorder itself or of the seizure disorder that is common in SWS. We compared
      two groups of children with SWS-- one with seizures (n=20) and one without
      seizures (n=14)--on parent-report and teacher-report measures of behavioral and
      academic functioning. The two subgroups were compared with each other as well as
      with children with epilepsy alone (n=29) and a group of healthy controls (n=21).
      The SWS group with seizures was more impaired than the seizure-free group on 9 of
      15 measures and the children with seizures were 10 times as likely to have
      received special education services. Overall, children with SWS and seizures were
      similar to the epilepsy group, whereas children with SWS and no seizures were
      similar to the controls.

PMID- 23000107
TI  - On a fully closed state of native human type-1 VDAC enriched in Nonidet P40.
AB  - There is indication that human type-1 VDAC/Porin31HL complexes, when purified
      from highly enriched cell membrane preparations of human B-lymphocytes by
      classical ion-exchange chromatography in the detergent Nonidet P40, rest in fully
      closed state, its N-terminus being accessible for mAbs. Cholesterol appears to be
      involved as a channel modulator. The channel switches to anion-selective or "open
      state" while being incorporated into black membranes at zero transmembrane
      potential. In this case, its N-terminus is hidden in the channel lumen. The
      cation-selective or "closed state" can be induced by transmembrane potentials
      beyond 30 mV, the N-terminus putatively now being positioned outside the channel
      lumen. The latter situation might allow one to decide if type-1 VDAC,
      preincubated with adequate antibodies against its N-terminal part, would enter
      black membranes in fully closed state or stay in the application medium,
      respectively, may be complexed to dimers.

PMID- 23000108
TI  - Remarkably low fibroblast acid alpha-glucosidase activity in three adults with
      Pompe disease.
AB  - INTRODUCTION: Most adults with Pompe disease are compound heterozygotes in which
      one acid alpha-glucosidase (GAA) allele harbors the c.-32-13T>G mutation, causing
      partial loss of GAA, and the other allele harbors a fully deleterious mutation.
      The fibroblast GAA activity in these patients is usually between 5% and 25% of
      the average in healthy individuals. In some adult patients, however, the
      fibroblast GAA activity is much lower and is in the range that is normally
      observed in classic-infantile Pompe disease. We investigated the genotype
      phenotype correlation in three such adult patients and measured the GAA activity
      as well as the glycogen content in muscle and fibroblasts in order to better
      understand the clinical course. METHODS: DNA was sequenced and GAA activity and
      glycogen content were measured in leukocytes, fibroblasts and muscle. Muscle
      biopsies were microscopically analyzed and the biosynthesis of GAA in fibroblasts
      was analyzed by immunoblotting. GAA activity and glycogen content in fibroblasts
      and muscle tissue in healthy controls, adult patients with Pompe disease and
      classic-infantile patients were compared with those of the three index patients.
      RESULTS: One patient had genotype c.525delT/c.671G>A (r.0/p.Arg224Gln). Two
      affected brothers had genotype c.569G>A/c.1447G>A (p.Arg190His/p.Gly483Arg). In
      all three cases the GAA activity and the glycogen content in fibroblasts were
      within the same range as in classic-infantile Pompe disease, but the activity and
      glycogen content in muscle were both within the adult range. In fibroblasts, the
      first step of GAA synthesis appeared unaffected but lysosomal forms of GAA were
      not detectable with immunoblotting. CONCLUSION: Some adult patients with
      mutations other than c.-32-13T>G can have very low GAA activity in fibroblasts
      but express higher activity in muscle and store less glycogen in muscle than
      patients with classic-infantile Pompe disease. This might explain why these
      patients have a slowly progressive course of Pompe disease.

PMID- 23000109
TI  - Inside a synesthete's head: a functional connectivity analysis with grapheme
      color synesthetes.
AB  - Grapheme-color synesthesia is a condition in which letters are perceived with an
      additional color dimension. To identify brain regions involved in this type of
      synesthesia and to analyze functional connectivity of these areas, 18 grapheme
      color synesthetes and 18 matched controls were stimulated with letters and pseudo
      letters presented in black and color in an event-related fMRI experiment. Based
      on the activation-differences between synesthetes and non-synesthetic controls
      regions of interest were defined. In a second analysis step functional
      connectivity was calculated using beta series correlation analysis for these seed
      regions. First we identified one seed region in the left inferior parietal (IPL)
      cortex (BA7) showing activation differences between grapheme-color synesthetes
      and controls. Furthermore, we found activation differences in brain areas
      involved in processing of letters and pseudo-letters, in particular the right IPL
      cortex (BA7), but also two more clusters in the right hemispheric BA 18 and BA
      40. Functional connectivity analysis revealed an increased connectivity between
      the left IPL seed region and primary/secondary visual areas (BA 18) in
      synesthetes. Also the right BA 7 showed a stronger connectivity with
      primary/secondary visual areas (BA 18) in grapheme-color synesthetes. The results
      of this study support the idea that the parietal lobe plays an important role in
      synesthetic experience. The data suggest furthermore that the information flow in
      grapheme-color synesthetes was already modulated at the level of the primary
      visual cortex which is different than previously thought. Therefore, the current
      models of grapheme-color synesthesia have to be refined as the unusual
      communication flow in synesthetes is not restricted to V4, fusiform cortex and
      the parietal lobe but rather involves a more extended network.

PMID- 23000110
TI  - Changes of cell electrical parameters induced by electroporation. A
      dielectrophoresis study.
AB  - Dielectrophoresis was employed to distinguish the electroporated from non
      electroporated cells. It was found that the electric field frequency at which
      cells change the direction of their movement (the crossover frequency f(CO)) is
      higher when cells are electroporated. The contribution to the cell
      dielectrophoretic behavior of four electric and geometrical cell parameters was
      analyzed using a single shell model. f(CO) measurements were performed in media
      with conductivities of 0.001-0.09S/m, on B16F10 cells which were electroporated
      in a Mannitol solution (0.001S/m), using rectangular or exponential pulses. The
      control cells' f(CO) was found in a domain of 2 to 105 kHz, while the
      electroporated cells' f(CO) was in a domain of 5 to 350 kHz, depending on the
      external media conductivities. At exterior conductivities above ~0.02S/m, f(CO)
      of electroporated cells became significantly higher compared to controls. Even
      though the possible contribution of membrane permittivity to explain the observed
      f(CO) shift toward higher values cannot be excluded, the computations highlight
      the fact that the variation of cytosol conductivity might be the major
      contributor to the dielectrophoretic behavior change. Our experimental
      observations can be described by considering a linear dependence of
      electroporated cells' cytosol conductivity against external conductivity.

PMID- 23000111
TI  - Tracking the molecular epidemiology of Brazilian Infectious bursal disease virus
      (IBDV) isolates.
AB  - Infectious bursal disease is a highly contagious disease of young chickens caused
      by Infectious bursal disease virus (IBDV). Genome segment A encodes the capsid
      protein (VP2), while segment B encodes the RNA-dependent RNA polymerase (VP1). In
      the present study, we trace the molecular epidemiology of IBDV in Brazil by
      analyzing 29 isolates collected in the major regions of poultry production. To
      genetically characterize the isolates, phylogenetic and population dynamic
      analyses were conducted using 68 VP1 (2634 nt) and 102 VP2 (1356 nt) coding
      sequences from IBDV isolates from different regions of the world. Furthermore,
      the evolution of IBDV was analyzed by characterizing the selective forces that
      operated during the diversification of viral isolates. We show that IBDV isolates
      were introduced into Brazil mainly from the Netherlands and the USA. These
      introductions were associated with all Brazilian poultry production regions
      analyzed in this work. In addition, we show that the evolution of IBDV has been
      shaped by a combination of very low recombination rates and relatively high rates
      of nucleotide substitution (2.988*10(-4) for VP1 and 3.2937*10(-4) for VP2),
      which themselves are a function of purifying selection operating on VP1 and VP2.
      Furthermore, our extended Bayesian skyline plot suggests that the increase in the
      effective population size of isolates of IBDV is consistent with its
      epidemiological history, with a large increase during the emergence of acute
      outbreaks of IBD in the 1980s.

PMID- 23000113
TI  - The influence of compatibility of traditional Chinese medicine on the
      pharmacokinetic of main components in Fructus aurantii.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Aurantii is one of the commonly used
      traditional Chinese medicines and the compatibility of Fructus Aurantii, Radix et
      Rhizoma Rhei and Semen Crotonis Pulveratum were the main components in a Chinese
      traditional patent medicine Weichang'an pill. Naringin and neohesperidin are two
      main flavonoid glycosides in the extract of Fructus Aurantii. The
      pharmacokinetics of naringin and neohesperidin, as the main marker constituents
      were analysis by a simple and accurate method. MATERIALS AND METHODS: In the
      present study, pharmacokinetic differences of two flavonoid glycosides were
      detected after oral administration of the extract of single herb and different
      compatibility of Fructus Aurantii, Radix et Rhizoma Rhei and Semen Crotonis
      Pulveratum which at doses of approximately 700 mg/kg naringin and 300 mg/kg
      neohesperidin. RESULTS: It indicated that the pharmacokinetic process of naringin
      and neohesperidin in four groups were demonstrated bimodal phenomenon after oral
      administration. Comparing to pharmacokinetic parameters of the single herbs
      administration, there were no significant difference after the compatibility of
      Fructus Aurantii and Radix et Rhizoma Rhei. However, the absorption of two
      flavonoid glycosides was increased dramatically after the compatibility of
      Fructus Aurantii or Semen Crotonis Pulveratum. The same results were attained
      after co-administration of the extract of three herbs. CONCLUSION: Some
      components in the extract of Semen Crotonis Pulveratum promoted the absorption of
      naringin and neohesperidin.

PMID- 23000112
TI  - Analysis of salivary gland transcripts of the sand fly Lutzomyia ayacuchensis, a
      vector of Andean-type cutaneous leishmaniasis.
AB  - The saliva of blood sucking insects contains potent pharmacologically active
      components that assist them in counteracting the host hemostatic and inflammatory
      systems during blood feeding. In addition, sand fly salivary proteins affect host
      immunity and have the potential to be a vaccine against Leishmania infection. In
      the present study, the salivary gland transcripts of Lutzomyia ayacuchensis, a
      vector of cutaneous leishmaniasis in Ecuadorian and Peruvian Andes, were analyzed
      by sequencing randomly selected clones of the salivary gland cDNA library of this
      sand fly. This resulted in the identification of the most abundant transcripts
      coding for secreted proteins. These proteins were homologous to the salivary
      molecules present in other sand flies including the RGD-containing peptide,
      PpSP15/SL1 family protein, yellow-related protein, putative apyrase, antigen 5
      related protein, D7 family protein, and 27 kDa salivary protein. Of note,
      homologues of maxadilan, an active vasodilator abundantly present in saliva of
      Lutzomyia longipalpis, were not identified. This analysis is the first
      description of salivary proteins from a sand fly of the subgenus Helcocyrtomyia
      and from vector of cutaneous leishmaniasis in the New World. The present analysis
      will provide further insights into the evolution of salivary components in blood
      sucking arthropods.

PMID- 23000114
TI  - Three Chinese herbal medicines promote neuroproliferation in vitro, and reverse
      the effects of chronic mild stress on behavior, the HPA axis, and proliferation
      of hippocampal precursor cell in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The present study investigated whether Chinese
      herbal medicines (CHMs) could reverse the effects of chronic mild stress (CMS) in
      a depression-like mouse model. MATERIALS AND METHODS: The effects of three
      Chinese herbals, Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri on
      promoting neuroproliferation were evaluated in vitro first and followed by in
      vivo study of mice which were received by an experimental setting of CMS for 14
      days. The effects of the three CHMs on depression were evaluated using a
      behavioral test, named a forced swimming test (FST). The possible anti-depressive
      mechanisms of these three CHMs, including the modulation of HPA axis and
      promoting the hippocampal precursor cell proliferation, were evaluated by
      measuring plasma corticosterone levels and BrdU incorporation. RESULTS: The in
      vitro results of MTS assay showed that Rhizome Chuanxiong, Radix Scutellaria and
      Radix Phellodendri could promote the proliferation of neural stem cells (NSCs) in
      a concentration-dependent manner. The oral administration of these three CHMs for
      14 days reversed not only the elevation of plasma corticosterone levels and body
      weight loss, but also the decreasing of hippocampal precursor cell proliferation
      and abnormal behavior in the CMS induced depression-like mouse model. CONCLUSION:
      These results indicated that Rhizome Chuanxiong, Radix Scutellaria and Radix
      Phellodendri have the potential to ameliorate depression. The possible mechanisms
      were the inhibition of HPA axis hyperactivity and the increasing of hippocampal
      precursor cell proliferation. These findings supported the multicomponent and
      multitargeted approach of Chinese herbal medicine.

PMID- 23000115
TI  - Safety assessment of aqueous extract from leaf Smallanthus sonchifolius and its
      main active lactone, enhydrin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Smallanthus sonchifolius (Poepp. &
      Endl.) H. Robinson (yacon) have been used since pre-Columbian times in the Andean
      region to prepare medicinal herbal tea with beneficial health properties.
      However, there are still disagreements about the safe use. This work was carried
      out to evaluate the toxicity profile of both, 10% decoction of yacon leaves and
      their major active lactone, enhydrin. MATERIALS AND METHODS: In vitro
      cytotoxicity assays were performed with Hep-G2, COS1, CHO-K1 and Vero cell lines
      using a test of metabolic competence based upon assessment of mitochondrial
      performance. In vivo toxicity study was performed in adult Wistar rats. In the
      acute oral toxicity each group of rats was orally given a single dose of 10%
      decoction or enhydrin. General condition, behavior and mortality were recorded
      for up to 14 days post treatment. In subchronic toxicity studies, both products
      were given orally for 90 days to rats. Body weight and food intakes were observed
      weekly. Hematological, clinical chemistry parameters and organ weight were
      determined in all animals at the end of the experimental period. RESULTS: Cell
      viability decreased in a concentration dependent fashion when cells were
      incubated with 2-200 MUg of 10% decoction and 0.015-7.5 MUg of enhydrin. In acute
      study in rats, there were no deaths or signs of toxicity observed after oral
      administration of single doses of 10% decoction or enhydrin at any dose level up
      to the highest dose tested (14.0 g/kg and 0.32 g/kg, respectively). In subchronic
      studies in rats, both products administered orally for 90 days at daily doses of
      0.07, 0.14 and 0.28 g 10% decoction/kg and 0.4, 0.8 and 8.0 mg enhydrin/kg, did
      not caused haematological, biochemical and histological alterations. CONCLUSIONS:
      The results presented in this paper lead us to the conclusion that the use of 10%
      decoction and enhydrin is safe in rat at doses in which it is demonstrated the
      hypoglycaemic effect.

PMID- 23000116
TI  - Prostate cancer specific survival in the Prostate, Lung, Colorectal, and Ovarian
      (PLCO) Cancer Screening Trial.
AB  - BACKGROUND: The prostate component of the Prostate, Lung, Colorectal, and Ovarian
      (PLCO) randomized screening trial demonstrated no mortality effect of screening.
      Here we analyze prostate cancer specific survival in PLCO and its relation to
      screening. METHODS: 76,693 men aged 55-74 were randomized to usual care (n =
      38,350) or intervention (n = 38,343). Intervention arm men received annual
      prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were
      followed for cancer diagnosis and mortality through 13 years. Medical record
      abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate
      specific survival in PLCO cases was analyzed using Kaplan-Meier analysis and
      proportional hazards modeling. We utilized data from the Surveillance,
      Epidemiology and End Results (SEER) program to compute expected survival in PLCO
      and compared this to observed. RESULTS: There was no significant difference in
      prostate-specific survival rates between arms; 10 year survival rates were 94.7%
      (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within
      the intervention arm, cases never screened in PLCO had lower 10 year survival
      rates (82%) than screen detected or interval (following a negative screen) cases,
      both around 95.5%. The ratio of observed to expected 10 year prostate-specific
      death (1-survival) rates was 0.59 (95% CI: 0.51-0.68) for all PLCO cases, 0.66
      (95% CI: 0.51-0.81) for Gleason 5-7 cases and 1.07 (95% CI: 0.87-1.3) for Gleason
      8-10 cases. CONCLUSION: Prostate cancer specific survival in PLCO was comparable
      across arms and significantly better than expected based on nationwide population
      data. How much of the better survival is due to a healthy volunteer effect and to
      lead-time and overdiagnosis biases is not readily determinable.

PMID- 23000117
TI  - Chemotaxis of T-cells after infection of human choroid plexus papilloma cells
      with Echovirus 30 in an in vitro model of the blood-cerebrospinal fluid barrier.
AB  - Enterovirus is the most common pathogen causing viral meningitis especially in
      children. Besides the blood-brain barrier (BBB) the choroid plexus, which forms
      the blood-cerebrospinal-fluid (CSF) barrier (BCSFB), was shown to be involved in
      the pathogenesis of enteroviral meningitis. In a human in vitro model of the
      BCSFB consisting of human choroid plexus papilloma cells (HIBCPP), the
      permissiveness of plexus epithelial cells for Echovirus 30 (EV30) was analyzed by
      immunoblotting and quantitative real-time PCR (Q-PCR). HIBCPP could be directly
      infected by EV30 from the apical as well as from the physiological relevant
      basolateral side. During an infection period of 5h no alterations of barrier
      function and cell viability could be observed. Analysis of the cytokine/chemokine
      profile following enteroviral infection with a cytometric bead array (CBA) and Q
      PCR revealed an enhanced secretion of PanGRO (CXCL1, CXCL2 and CXCL3), IL8 and
      CCL5. Q-PCR showed a significant upregulation of CXCL1, CXCL2 and CXCL3 in a time
      dependant manner. However, there was only a minor effect of HIBCPP-infection with
      EV30 on transepithelial T lymphocyte migration with or without the
      chemoattractant CXCL12. Moreover, CXCL3 did not significantly enhance T cell
      migrations. Therefore additional factors must be involved for the in vivo
      reported enhanced T cell migration into the CNS in the context of enteroviral
      meningitis. As HIBCPP are permissive for infection with EV30, they constitute a
      valuable human in vitro model to study viral infection at the BCSFB.

PMID- 23000118
TI  - Development of a loudness normalisation strategy for combined cochlear implant
      and acoustic stimulation.
AB  - Users of a cochlear implant together with a hearing aid in the non-implanted ear
      currently use devices that were developed separately and are often fitted
      separately. This results in very different growth of loudness with level in the
      two ears, potentially leading to decreased wearing comfort and suboptimal
      perception of interaural level differences. A loudness equalisation strategy,
      named 'SCORE bimodal', is proposed. It equalises loudness growth for the two
      modalities using existing models of loudness for acoustic and electric
      stimulation, and is suitable for implementation in wearable devices. Loudness
      balancing experiments were performed with six bimodal listeners to validate the
      strategy. In a first set of experiments, the function of each loudness model used
      was validated by balancing the loudness of four harmonic complexes of different
      bandwidths, ranging from 200 Hz to 1000 Hz, separately for each ear. Both the
      electric and acoustic loudness models predicted the data well. In a second set of
      experiments, binaural balancing was done for the same stimuli. It was found that
      SCORE significantly improved binaural balance.

PMID- 23000120
TI  - Structural perturbation of diphtheria toxoid upon adsorption to aluminium
      hydroxide adjuvant.
AB  - Aluminium-containing adjuvants are often used to enhance the potency of vaccines.
      In the present work we studied whether adsorption of diphtheria toxoid to
      colloidal aluminium hydroxide induces conformational changes of the antigen.
      Diphtheria toxoid has a high affinity for the aluminium hydroxide particles based
      on a high adsorption degree, adsorption rate and adsorptive capacity. The
      conformation and stability of diphtheria toxoid in solution and adsorbed to
      aluminium hydroxide adjuvant were characterized using five physicochemical
      techniques: intrinsic and extrinsic fluorescence spectroscopy, circular
      dichroism, infrared spectroscopy and differential scanning calorimetry.
      Diphtheria toxoid adsorbed to aluminium hydroxide resulted in a minimal shift of
      the tryptophan fluorescence spectrum, whereas a large increase in the emission of
      the Bis-ANS probe was observed, indicating that hydrophobic sites of the protein
      became accessible due to adsorption. In addition, circular dichroism and infrared
      spectroscopy revealed that adsorption to aluminium hydroxide caused an increase
      of beta-sheet content and a decrease of alpha-helix content in diphtheria toxoid.
      Differential scanning calorimetry demonstrated a major decrease in the enthalpy
      of denaturation upon adsorption. In conclusion, the adsorption of diphtheria
      toxoid to aluminium hydroxide adjuvant leads to substantial conformational
      changes in the antigen. Since physicochemical methods can be used to monitor
      these conformational changes, these analytical methods might offer a tool in
      regulatory required vaccine quality control by demonstrating consistency in
      production.

PMID- 23000119
TI  - Decreased expression and increased oxidation of plasma haptoglobin in Alzheimer
      disease: Insights from redox proteomics.
AB  - Alzheimer disease (AD) is one of the most disabling disorders of the elderly and
      the number of people worldwide facing dementia is expected to dramatically
      increase in the near future. Thus, one of the major concerns of modern society is
      to identify putative biomarkers that serve as a valuable early diagnostic tool to
      identify a subset of patients with increased risk to develop AD. An ideal
      biomarker should be present in blood before dementia is clinically confirmed,
      have high sensitivity and specificity, and be reproducible. Proteomics platforms
      offer a powerful strategy to reach these goals and recently have been
      demonstrated to be promising approaches. However, the high variability of
      technologies and studied populations has led to contrasting results. To increase
      specificity, we analyzed both protein expression profiles and oxidative
      modifications (carbonylation) of plasma proteins in mild cognitive impairment
      (MCI) and AD subjects compared with age-matched controls. Most of the proteins
      found to have differential levels in MCI and AD confirmed results already
      obtained in other cohort studies. Interestingly, we applied for the first time in
      MCI a redox proteomics approach to specifically identify oxidized proteins. Among
      them, haptoglobin, one of the most abundantly secreted glycoproteins with
      chaperone function, was found to be either increasingly downregulated or
      increasingly oxidized in AD and MCI compared with controls. We also demonstrated
      that in vitro oxidation of haptoglobin affects the formation of amyloid-beta
      fibrils, thus suggesting that oxidized haptoglobin is not able to act as an
      extracellular chaperone to prevent or slow formation of amyloid-beta aggregates.
      Another chaperone protein, alpha2-macroglobulin, was found to be selectively
      oxidized in AD patients compared with controls. Our findings suggest that
      alterations in proteins acting as extracellular chaperones may contribute to
      exacerbating amyloid-beta toxicity in the peripheral system and may be considered
      a putative marker of disease progression.

PMID- 23000121
TI  - Conjugation of Y. pestis F1-antigen to gold nanoparticles improves
      immunogenicity.
AB  - The efficacy of 15 nm gold nanoparticles (AuNP) coated with Yersinia pestis F1
      antigen, as an immunogen in mice, has been assessed. The nanoparticles were
      decorated with F1-antigen using N-hydroxysuccinimide and N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride coupling chemistry. Mice
      given AuNP-F1 in alhydrogel generated the greatest IgG antibody response to F1
      antigen when compared with mice given AuNP-F1 in PBS or given unconjugated F1
      antigen in PBS or alhydrogel. Compared with unconjugated F1-antigen, the IgG2a
      response was enhanced in mice dosed with AuNP-F1 in PBS (p<0.05) but not in mice
      immunised with AuNP-F1 in alhydrogel. All treatment groups developed a memory
      response to F1-antigen, the polarity of which was inflenced by formulation in
      alhydrogel. The sera raised against F1-antigen coupled to AuNPs was able to
      competitively bind to rF1-antigen, displacing protective macaque sera.

PMID- 23000122
TI  - Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against
      invasive pneumococcal disease in the elderly in England and Wales.
AB  - In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high
      risk groups was extended to include all >= 65 year olds in England and Wales,
      starting with >= 80 year olds and moving to 75-79 and 65-74 year olds by 2005. We
      conducted an ecological study to assess the impact of the extended PPV23
      programme on serotype-specific incidence of invasive pneumococcal disease (IPD)
      and a case-control study to assess vaccine effectiveness (VE) using the national
      IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23
      serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes
      covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006
      declined in >= 65 year olds after 2006 but was offset by an increase in non-PCV7
      serotypes. This increase was similar for the additional 16 serotypes covered by
      PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained
      for controls (n=1270) with non-PPV23 IPD diagnosed between November 2003 and
      December 2010 and a subset of cases (n=1272) matched for age and time period. VE
      declined from 48% (95% confidence interval; 32-60%) within two years of
      vaccination to 15% (-3% to 30%) after five years. Although differences in VE by
      age and having risk conditions were not statistically significant the highest
      estimates were in the youngest age group (65-74 years) and in those without risk
      conditions with a VE estimate of 65% (23-84%) within 2 years of vaccination for
      non-risk 65-74 year olds. VE differed by serotype (p=0.005), from -23% (-85% to
      19%) for serotype 3 to 63% (29-81%) for 12F. In conclusion PPV23 was effective,
      particularly in healthy under 75 year olds, but protection waned after 5 years.
      There was no discernible impact of PPV23 on IPD incidence or PCV7-induced
      serotype replacement, consistent with the modest overall effectiveness, the 45%
      increased coverage over the former risk-based programme and lack of herd immunity
      from the PPV23 programme. Based on the VE estimates PPV23 was still considered a
      cost-effective intervention for the low risk elderly.

PMID- 23000123
TI  - The potential mechanism of Bursal-derived BPP-II on the antibody production and
      avian pre-B cell.
AB  - The bursa of Fabricius is critical for the normal development of the B
      lymphocytes responsible for antibody production. However, the mechanism of the
      bursal-derived bioactive factor on B cell development is little reported. In this
      paper, chicks were immunized with BPP-II and AIV vaccine or AIV antigen, and
      antibody and IL-4 production were detected. The results showed that BPP-II played
      strongly inducing roles on the humoral immune responses. To investigate the gene
      expression at transcriptional level, avian pre-B lymphocyte DT40 cells were
      treated with BPP-II, and were analyzed with the gene microarray. The results
      proved that BPP-II treatment regulated 11 pathways, in which homologous
      recombination is a vital mechanism which is involved in antibody Ig gene
      conversion and diversification during B cell development. These results suggested
      Bursal-derived biological active factor BPP-II might be involved in the antibody
      production processes and B cell development, which is vital to the humoral
      central immune organ, the bursa of Fabricius.

PMID- 23000124
TI  - Effect of an educational intervention on Hungarian adolescents' awareness,
      beliefs and attitudes on the prevention of cervical cancer.
AB  - The alarming national data on the mortality and morbidity rates of cervical
      cancer as well as the results of a Hungarian survey demonstrating adolescents'
      low level of understanding of human papillomavirus (HPV) infection and HPV
      vaccination encouraged the authors to conduct an educational intervention. The
      aim of this survey was to explore the impact of a brief, HPV-focused program on
      adolescents' knowledge, beliefs and attitudes. A self-administered anonymous
      questionnaire was completed by 394 male and female adolescents in September,
      2010, in Hungary. Half of the students (48.5%) then had a one-off educational
      intervention on aspects cervical cancer lasting 45 min lesson, while the rest of
      the participants, the control group, did not have the educational intervention.
      Three months following the education, both groups were retested using the same
      questionnaire. Data were analysed using Statistical Package for the Social
      Sciences (SPSS). Following the education, significant increase was detected in
      cervical cancer awareness: causal relationship between HPV and cervical cancer
      (7.9% -> 22.1%, p<0.05), or perception of HPV vaccination (61.3% -> 85.9%,
      p<0.05). Similarly, health-related beliefs have enhanced, such as 'HPV may cause
      cervical cancer' (64.9% -> 81.0%, p<0.05) or 'cervical cancer may be prevented by
      vaccination' (66.5% -> 85.3%, p<0.05). Our data also highlighted that Hungarian
      adolescents have been practising extremely risky sexual behaviour. Nearly half of
      the sexually active adolescents had engaged in 'one-night relationship' (41.1%)
      as well as having sexual intercourse without any contraceptive safety measures
      (44.3%). In addition to providing adolescents with clear and meaningful
      information about the implications of a HPV infection and addressing their fears
      of screening and vaccination, health education should focus on promoting safe sex
      behaviour by promoting the use of condoms and reducing the number of sexual
      partners to limit the spread of HPV, and also on encouraging the participation in
      regular cervical screenings, thus reducing the incidence of cervical cancer.

PMID- 23000125
TI  - The role of nasal IgA in children vaccinated with live attenuated influenza
      vaccine.
AB  - BACKGROUND: Immunoglobulin A (IgA) is the predominant antibody produced in
      response to mucosal infections. The role of IgA in providing protection against
      influenza in children vaccinated with live attenuated influenza vaccine (LAIV)
      has not been well described. METHODS: Nasal IgA responses were assessed using
      data from 3 prospective, 2-year, randomized studies comparing LAIV with placebo
      in children 6-36 months of age. In each study, samples were collected in a subset
      of patients; a new cohort was enrolled each year. Ratios of strain-specific nasal
      IgA to total nasal IgA were calculated and prevaccination to postvaccination
      geometric mean fold-rises (GMFRs) were evaluated. Mean postvaccination IgA ratios
      were compared for subjects with and without confirmed influenza illness by study
      and in pooled analyses. RESULTS: Across studies, a higher percentage of children
      receiving LAIV had a >= 2-fold increase in strain-specific IgA ratio compared
      with placebo recipients. GMFRs after LAIV in years 1 and 2 ranged from 1.2 to
      6.2, compared with 0.5-2.2 among placebo recipients. Similar responses were
      observed in subjects who were baseline seronegative and seropositive based on
      serum hemagglutination inhibition antibody titers. In years 1 and 2, the mean
      postvaccination strain-specific to total IgA ratio was 3.1-fold (P<0.01) and 2.0
      fold (P<0.03) higher among LAIV recipients with no evidence of culture-confirmed
      influenza illness compared with LAIV recipients who developed culture-confirmed
      influenza illness; a similar and consistent trend was observed for each
      individual study and type/subtype. CONCLUSIONS: The current analysis demonstrates
      that nasal IgA contributes to the efficacy of LAIV and can provide evidence of
      vaccine-induced immunity. However, the inherent heterogeneity in nasal antibody
      levels and variability in nasal specimen collection hinders the precise
      evaluation of mucosal antibody responses. Other studies have demonstrated that
      LAIV-induced immunity is also partially explained by T-cell immunity, serum
      antibody responses, and innate immunity, consistent with the multi-faceted nature
      of immunity induced by wild-type influenza infection and other live virus
      vaccines.

PMID- 23000126
TI  - Mice immunized with bone marrow-derived dendritic cells stimulated with
      recombinant Coxiella burnetii Com1 and Mip demonstrate enhanced bacterial
      clearance in association with a Th1 immune response.
AB  - The recombinant membrane-associated proteins of Coxiella burnetii, Com1, Mip and
      GroEL, were used in vitro to stimulate BALB/c mouse bone marrow-derived dendritic
      cells (BMDCs). The antigen-activated BMDCs were transferred into naive BALB/c
      mice. Seven days after challenge of C. burnetii, the bacterial loads of mice
      receiving BMDCs activated with Com1 or Mip, but not GroEL, were significantly
      lower than that of mice receiving BMDCs pulsed with TrxA (Esherichia coli
      thioredoxin) in a quantitative polymerase chain reaction assay. After in vitro
      interaction with cognate antigen-pulsed BMDCs, the percentages of CD69-positive
      cells and TNF-alpha-positive cells in CD4(+) and CD8(+) T cells isolated from the
      spleens of mice receiving Com1-, Mip-, or GroEL-pulsed BMDCs were significantly
      higher than that of mice receiving mock-pulsed BMDCs in flow cytometric analysis.
      The percentages of IFN-gamma-positive cells in CD4(+) and CD8(+) T cells from
      mice receiving Com1- or Mip-pulsed BMDCs were significantly greater than that of
      mice receiving GroEL-pulsed BMDCs. However, the percentage of IL-4-positive cells
      in CD4(+) T cells of mice receiving GroEL-pulsed BMDCs was obviously higher than
      that of mice receiving Com1- or Mip-pulsed BMDCs. Our results demonstrate that
      Com1 and Mip are protective antigens and strongly indicate that they favor to
      induce IFN-gamma-producing Th1 and Tc1 cells, whereas the non-protective antigen
      GroEL is biased to induce a Th2 response. Therefore, Com1 and Mip are key
      antigens to induce a protective immune response against C. burnetii infection.

PMID- 23000127
TI  - Effective protection against secondary pneumococcal pneumonia by oral vaccination
      with attenuated Salmonella delivering PspA antigen in mice.
AB  - Influenza infection followed by pneumococcal infection can cause severe pneumonia
      and this secondary pneumococcal pneumonia is the most common cause of influenza
      associated death. Therefore, vaccination against Streptococcus pneumoniae is
      highly desirable for reducing the disease burden caused by seasonal epidemic and
      pandemic influenza. In this study, mice were vaccinated orally with a recombinant
      attenuated Salmonella vaccine (RASV) strain that delivers pneumococcal surface
      protein A (PspA) in order to examine protective efficacy against secondary
      pneumococcal pneumonia. A single dose of oral RASV resulted in attenuated
      pulmonary inflammation and effective protection against secondary pneumococcal
      pneumonia. Additionally, oral RASV induced long-term protection against secondary
      pneumococcal pneumonia. Treatment with an antiviral drug (i.e., oseltamivir)
      after treatment with RASV further prevented pulmonary inflammation after
      secondary pneumococcal infection. These results imply that oral RASV can protect
      mice from secondary pneumococcal infection after influenza infection and that
      vaccination against respiratory bacterial pathogens is a promising approach for
      dampening the impact of annual epidemic and pandemic influenza outbreaks.

PMID- 23000128
TI  - Construction and immune effect of Haemophilus parasuis DNA vaccine encoding
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in mice.
AB  - Haemophilus parasuis, the causative agent of swine polyserositis, polyarthritis,
      and meningitis, is one of the most important bacterial diseases of pigs
      worldwide. The development of a vaccine against H. parasuis has been impeded due
      to the lack of induction of reliable cross-serotype protection. In this study the
      gapA gene that encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was shown
      to be present and highly conserved in various serotypes of H. parasuis and we
      constructed a novel DNA vaccine encoding GAPDH (pCgap) to evaluate the immune
      response and protective efficacy against infection with H. parasuis MD0322
      serovar 4 or SH0165 serovar 5 in mice. A significant antibody response against
      GAPDH was generated following pCgap intramuscular immunization; moreover,
      antibodies to the pCgap DNA vaccine were bactericidal, suggesting that it was
      expressed in vivo. The gapA transcript was detected in muscle, liver, spleen, and
      kidney of the mice seven days post-vaccination. The IgG subclass (IgG1 and IgG2a)
      analysis indicated that the DNA vaccine induced both Th1 and Th2 immune
      responses, but the IgG1 response was greater than the IgG2a response. Moreover,
      the groups vaccinated with the pCgap vaccine exhibited 83.3% and 50% protective
      efficacy against the H. parasuis MD0322 serovar 4 or SH0165 serovar 5 challenges,
      respectively. The pCgap DNA vaccine provided significantly greater protective
      efficacy compared to the negative control groups or blank control groups (P<0.05
      for both). Taken together, these findings indicate that the pCgap DNA vaccine
      provides a novel strategy against infection of H. parasuis and offer insight
      concerning the underlying immune mechanisms of a bacterial DNA vaccine.

PMID- 23000129
TI  - Avidity and subtyping of specific antibodies applied to the indirect assessment
      of heterologous protection against Foot-and-Mouth Disease Virus in cattle.
AB  - Serological assessment of the heterologous response among Foot-and-Mouth Disease
      Virus (FMDV) strains is mainly performed by virus neutralization test (VNT),
      liquid phase blocking ELISA and complement fixation assay. In this study two high
      throughput ELISA techniques, avidity and IgG subtype ELISA, were developed and
      used to further characterize heterologous antibody responses in cattle during
      vaccination and challenge. Both assays were applied to a set of previously
      characterized sera from animals immunized with an inactivated A24
      Cruzeiro/Brazil/55 (A24 Cruzeiro) strain monovalent FMDV vaccine and challenged
      with the heterologous A/Argentina/2001 (A/Arg/01) strain. Single dilution avidity
      ELISA assessment showed that animals that were protected against A/Arg/01
      challenge had higher avidity antibodies to this heterologous strain than non
      protected cattle. Animals with low or even undetectable anti-A/Arg/01 serum
      neutralizing titers that passed the heterologous challenge presented higher
      IgG1/IgG2 ratio than non-protected animals. In this study, the three assessments
      (VNT and both ELISAs) discriminated between protected and not protected animals
      against a heterologous challenge. The combination of these techniques may be
      applied to complement current indirect serological vaccine-matching assessments.
      The measurement of these qualitative parameters may provide additional
      information to understand the mechanisms underlying FMD heterologous responses
      and the induction of cross-protection in cattle.

PMID- 23000131
TI  - A self-propelling cycle mediated by reactive oxide species and nitric oxide
      exists in LPS-activated microglia.
AB  - It has been widely accepted that microglia, the innate immune cells in the brain,
      can be chronically activated in response to neuron death, fuelling a self
      renewing cycle of microglial activation followed by further neuron damage
      (reactive microgliosis), which has been considered as the main reason responsible
      for the progressive nature of neurodegenerative diseases. In the present study,
      it was found that LPS (lipopolysaccharide) significantly induced the activation
      of N9 microglia, and the increase of NO level induced by pretreatment of LPS
      could last after the removal of LPS. The culture medium of activated microglia
      significantly decreased the viability of rat primary cortical neuron. These
      results can be blocked by the antioxidant N-acetylcysteine (NAC) and nicotinamide
      adenine dinucleotide phosphate reduced (NADPH) oxidase inhibitor
      diphenyleneiodonium sulfate (DPI), suggesting that intracellular reactive oxide
      species (iROS) released from the activated microglial cells may continue to
      further activate microglia. Next, it was shown that the iROS level increased
      rapidly after the LPS treatment in microglia cells followed by the NO production
      through the regulation of iNOS (inducible nitric oxide synthase) expression. The
      increase of iROS could be reversed by gp91phox (the critical and catalytic
      subunit of NADPH oxidase) siRNA. Moreover, NO released from sodium nitroprusside
      (SNP) was able to increase the iROS production of N9 microglia by regulating of
      the activity and the expression of NADPH oxidase. In conclusion, our research
      suggests for the first time that there may exist a self-propelling cycle in
      microglial cells possibly mediated by iROS and NO when they become activated by
      LPS. It may be responsible partially for the ongoing microglial activation and
      the progressive nature of neurodegenerative diseases.

PMID- 23000130
TI  - Flagellin-HA vaccines protect ferrets and mice against H5N1 highly pathogenic
      avian influenza virus (HPAIV) infections.
AB  - In order to meet the global demand for rapid production of pandemic influenza
      vaccines, we have developed a recombinant fusion vaccine platform in which the
      globular head of hemagglutinin (HA) antigen is genetically fused to bacterial
      flagellin (a TLR5 ligand). These flagellin-HA fusion vaccine candidates elicit
      highly protective immunity against a lethal challenge with 2009 pandemic H1N1
      (Liu, et al. PLoS ONE 2011; 6:e20928) or H5N1 influenza A/Vietnam/1203/04 (A/VN)
      infections in mice (Song, et al. Vaccine 2009;27:5875-88). Here we provide the
      first evidence showing that two A/VN vaccine candidates elicited HA-specific IgG,
      reduced nasal virus shedding, and conferred full protection against a lethal A/VN
      infection in ferrets. Furthermore, we show that similar flagellin-HA vaccine
      candidates of two other H5N1 HPAIV are immunogenic and/or efficacious in mice.
      Vaccines of A/Indonesia/5/05 (A/IN) induced significant HAI titers to homologous
      and heterologous A/Anhui/1/05 (A/AN) H5N1 viruses. Two subcutaneous immunizations
      with doses of either 0.3 MUg or 3 MUg of A/IN candidates resulted in >= 2.5
      log(10) unit reduction in day 5 lung virus titer and 90-100% protection against a
      lethal A/IN challenge in mice. Both R3.HA5 IN and R3.2xHA5 IN vaccines elicited
      robust neutralizing antibody responses that last for at least 9 months and
      demonstrated a significant anamnestic antibody response upon further booster
      immunization. Finally, we found that two vaccine candidates of A/AN induced
      significant HAI titers in mice. Taken together, our recombinant flagellin-HA
      platform has been successfully used to generate potent H5N1 HPAIV vaccine
      candidates. These promising preclinical results justify the advancement of these
      candidates into the clinic.

PMID- 23000132
TI  - The consequences of progressive phonological impairment for reading aloud.
AB  - The 'primary systems' view of reading disorders proposes that there are no neural
      regions devoted exclusively to reading, and therefore that acquired dyslexias
      should reliably co-occur with deficits in more general underlying capacities.
      This perspective predicted that surface dyslexia, a selective deficit in reading
      aloud 'exception' words (those with atypical spelling-sound characteristics),
      should be a consistent feature of semantic dementia, a progressive disorder of
      conceptual knowledge, and just such a pattern has been observed in previous
      research. In a similar vein, one might expect the gradual deterioration of
      phonological processing seen in the nonfluent forms of progressive aphasia to be
      accompanied by phonological dyslexia, a selective deficit in reading of
      unfamiliar letter strings, i.e., nonwords. The present study, reporting a case
      series consideration of reading-aloud data from 16 progressive nonfluent aphasic
      patients, revealed a pattern in which both low-frequency exception word and
      nonword reading were comparably compromised. The severity of the reading disorder
      was predicted by scores on the expressive language task of picture naming but not
      the receptive task of spoken word-to-picture matching. Our hypothesis that a
      phonological deficit underpins diminished performance for both naming and reading
      was supported by the finding that reading-aloud performance was predicted
      specifically by the rate of phonological errors in picture naming. Moreover, the
      strength of this relationship was similar for low-frequency exception words and
      nonwords, suggesting that reading deficits for these two types of items in this
      disorder shared a common cause: a progressive impairment of phonological
      processing.

PMID- 23000133
TI  - Music-based memory enhancement in Alzheimer's disease: promise and limitations.
AB  - In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients
      with Alzheimer's disease (AD) better recognized visually presented lyrics when
      the lyrics were also sung rather than spoken at encoding. The present study
      sought to further investigate the effects of music on memory in patients with AD
      by making the content of the song lyrics relevant for the daily life of an older
      adult and by examining how musical encoding alters several different aspects of
      episodic memory. Patients with AD and healthy older adults studied visually
      presented novel song lyrics related to instrumental activities of daily living
      (IADL) that were accompanied by either a sung or a spoken recording. Overall,
      participants performed better on a memory test of general lyric content for
      lyrics that were studied sung as compared to spoken. However, on a memory test of
      specific lyric content, participants performed equally well for sung and spoken
      lyrics. We interpret these results in terms of a dual-process model of
      recognition memory such that the general content questions represent a
      familiarity-based representation that is preferentially sensitive to enhancement
      via music, while the specific content questions represent a recollection-based
      representation unaided by musical encoding. Additionally, in a test of basic
      recognition memory for the audio stimuli, patients with AD demonstrated equal
      discrimination for sung and spoken stimuli. We propose that the perceptual
      distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients
      via a non-selective distinctiveness heuristic, thereby reducing false recognition
      while at the same time reducing true recognition and eliminating the mnemonic
      benefit of music. These results are discussed in the context of potential music
      based memory enhancement interventions for the care of patients with AD.

PMID- 23000134
TI  - The influence of motor and cognitive impairment upon visually-guided saccades in
      Parkinson's disease.
AB  - Studies of saccades in Parkinson's disease (PD) have seldom examined the
      influence of cognitive status, ranging from normal cognition, through mild
      cognitive impairment, to dementia. In a large and heterogeneous sample, we
      examined how motor and cognitive impairment was reflected in the performance of
      reflexive, visually-guided saccades. We examined 163 people with PD and 47
      similar-aged controls. Ninety three of the PD group had normal cognition (PDN),
      48 had mild cognitive impairment (PD-MCI), and 22 had dementia (PDD). Pseudo
      random targets (amplitudes of 5, 10, 15 and 20 deg and inter-stimulus-intervals
      ranging from 550 to 1800 ms) were shown in 108 mixed randomised trials,
      incorporating gap, step, and overlap onset conditions. Analyses were conducted
      using multi-level regression modeling. Participants were first assessed by
      continuous measures (Unified PD Rating Scale motor score and the Montreal
      Cognitive Assessment). Prolonged latency was significantly related to both motor
      and cognitive impairment, with the cognitive effect being compounded by
      increasing age. Decreased saccade amplitude, meanwhile, was primarily related to
      motor impairment. When assessed by discrete cognitive categories, all of the PD
      groups showed reduced saccadic amplitude relative to controls. Saccadic
      latencies, meanwhile, were abnormally prolonged only in the PD-MCI and PDD groups
      (the control and PDN groups were similar to each other). Latency in the overlap
      task was particularly sensitive to increasing motor and cognitive impairment. We
      conclude that reflexive saccades in PD are subtly decreased in amplitude even
      early in the disease process. Prolonged saccade latency, meanwhile, tends to
      occur later in the disease process, in the presence of more substantial motor and
      cognitive impairment, and greater age. The progressive impairment of reflexive
      saccades, and the differential onset of amplitude and latency impairments, may
      make them a useful objective tool for assessing disease status.

PMID- 23000135
TI  - Protective role of autophagy in branched polyethylenimine (25K)- and poly(L
      lysine) (30-70K)-induced cell death.
AB  - Polyethylenimine (PEI) and poly(L-lysine) (PLL), which are cationic polymers used
      for gene therapy, are known to be cytotoxic, but their molecular mechanisms of
      cell death are not fully understood. In this study, we provide evidence that PEI
      and PLL induced autophagy in HeLa cervical cancer cells. In cells overexpressed
      with green fluorescent protein (GFP)-microtubule-associated protein 1 light chain
      3 (LC3) fusion protein, PEI and PLL induced fluorescent puncta formations that
      represent LC3 recruitment to autophagosomes. In Western blot analysis,
      conversions of the LC3-I to LC3-II were significant, and p62 degradation was
      observed in cells treated with PEI and PLL. At higher doses, the ability of
      endosomal escape by PEI facilitates the conversion of LC3-I to LC3-II without the
      use of lysosomal protease inhibitors. From the analysis of annexin V-flourescein
      isothiocyanate (FITC) and propidium iodide (PI) staining by flow cytometry, both
      apoptosis and necrosis occurred in PEI- and PLL-treated cells. Significant
      activated caspase-3 expression was detected in PLL- and PEI-treated cells. By
      applying Z-VAD apoptotic inhibition, apoptosis and autophagy may occur
      independently or autophagy may be in the upstream of apoptosis on PEI- and PLL
      treated cells. The degree of cell death was higher in incubated HeLa cells
      treated with PEI or PLL plus autophagy inhibitors (3-methyladenine (3-MA) and
      wortmannin). Treatment with these autophagy inhibitors, however, did not inhibit
      LC3-II formation specifically. In addition, PEI and PLL induced higher degree of
      cell death in atg5(-/-) mouse embryonic fibroblast (MEF) cells than in wild-type
      cells. Autophagy was also induced in PEI- and PLL-treated MEFs, as evidenced by
      the formation of LC3-II in wild-type-but not in atg5(-/-) MEFs. These results
      indicate that PEI and PLL can trigger both death and survival pathways
      simultaneously, and autophagy played a role in cell survival in PEI- and PLL
      treated cells. Our study therefore provides deeper insight into the molecular
      mechanisms of cell death caused by cationic polymers.

PMID- 23000136
TI  - Two cases of suicide by asphyxiation due to helium and argon.
AB  - Numerous death cases due to suffocation in a toxic or oxygen deficient gas
      atmosphere have been described in the literature, but unfortunately especially
      cases involving inert gases like helium are often presented without detailed
      toxicological findings. Observations on two suicides are reported, one by helium
      and the other by argon inhalation. During autopsies gas samples from the lungs
      were collected directly into headspace vials by a procedure ensuring minimal loss
      and dilution. Qualitative gas analyses were performed using headspace gas
      chromatography-mass spectrometry (HS-GC/MS). For carrier gas the commonly used
      helium was replaced by hydrogen. Qualitative positive results were obtained in
      the argon case, but the case involving helium revealed negative findings. The use
      of HS-GC/MS enables in principle to detect inert gases like argon or helium.
      However, a number of factors may later influence the results as, e.g. a longer
      period of time between death and sampling or pre-analytical artefacts during
      sampling of such highly volatile substances. In absence of analytical data
      supporting helium exposure, the causes of death in the actual cases were found to
      be asphyxia and in both cases the manner was suicide.

PMID- 23000137
TI  - The pathogenetic role of adulterants in 5 cases of drug addicts with a fatal
      outcome.
AB  - The purpose of the present study is to determine the role of lidocaine, caffeine
      and dextromethorphan, used as adulterant substances, in five cases of drug
      overdose which have come to our attention. Taking into account the
      pharmacological mechanism, blood concentration and route of administration
      (intravenous) we evaluated the hypothesis that these substances could act with a
      synergistic effect - or at least additive - with the illicit drugs on the central
      nervous system and cardiovascular system.

PMID- 23000138
TI  - Prescription and illicit psychoactive drugs in oral fluid--LC-MS/MS method
      development and analysis of samples from Brazilian drivers.
AB  - This study is part of a larger project designed to investigate the prevalence of
      psychoactive drug (PAD) use among Brazilian drivers. In this paper we describe
      the development and validation of an analytical method to analyze 32 prescription
      and illicit PADs (amphetamines, benzodiazepines, cocaine, cannabis, opioids,
      ketamine and m-CPP) and metabolites in oral fluid samples collected with a
      QuantisalTM device. Samples were extracted with ethyl acetate:hexane and analyzed
      by LC-MS/MS. Instrumental LOD ranged from 0.26 to 0.65 ng/mL. Mean procedural
      recoveries at 1.3 ng/mL (LLOQ) ranged from 50% to 120% for 24 compounds.
      Recoveries were concentration independent, with the exception of femproporex,
      heroin and ecgonine methyl-ester (EME) for which the recovery decreased
      significantly at higher levels (13 and 52 ng/mL). RSD was <20% for all compounds
      at all spiking levels. Ion suppression due to the matrix was <20% for most
      compounds, and higher than 60% for EME and diethylpropion. Analysis was performed
      against a in-matrix standard curve. About 10% of the 2235 oral fluid samples
      collected from drivers on Brazilian Federal highways were positive (>=LOD) for at
      least one analyte investigated. Alone or in combination with other drugs,
      cocaine/metabolites were the analytes most detected in the samples (129; 5.8%),
      followed by amphetamines/metabolite (69; 3.1%), benzodiazepines (28; 1.2%),
      cannabinoids (23; 1.1%) and opioids (8; 0.4%). Detection of at least two PADs
      from different classes accounted for 9.3% of the 236 positive samples. Cocaine
      was found at higher levels in the samples (up to 1165 ng/mL). Preventive measures
      aimed at reducing the use of PADs by drivers in Brazil will certainly contribute
      to decrease the country's highway death rates.

PMID- 23000139
TI  - Preservation of Calliphora vicina (Diptera: Calliphoridae) pupae for use in post
      mortem interval estimation.
AB  - Post-mortem interval (PMI) is frequently calculated using immature stages of
      carrion frequenting Calliphoridae (Diptera). This is based on identification to
      species level, followed by age estimation of the samples. These two processes
      depend on suitable preservation of insects for subsequent analyses, yet
      preservation methods for the pupal stage are poorly defined and inappropriate
      methods may result in discolouration or nucleic acid degradation. This study
      examined the effects of 21 common preservation methods on Calliphora vicina pupae
      of 4 and 7d old, assessing consequences of the various methods for DNA-based
      species identification, age estimation using morphological analyses, and
      differential gene expression (DGE) studies. Pupae were examined within two weeks
      of preservation and again after 6-8 months. Of the methods tested, hot-water
      killing (HWK) followed by storage in 80% ethanol at -20 degrees C or 4 degrees C
      was the best treatment for external morphology and histological analyses
      respectively. DNA based species identification was possible following all
      methods. RNA integrity and amplification were best when pupae were stored at -80
      degrees C or in RNAlater (-20 degrees C), however HWK and storage in 80% ethanol
      at -20 degrees C was also acceptable, and thus the latter is proposed as a
      universal preservative method for pupae. This study proposes a preservation
      method for pupae that enables DNA-based species identification, internal and
      external morphological analysis for age estimation, and DGE study to be carried
      out on a single specimen, enabling a multidisciplinary approach to age estimation
      from a single pupa.

PMID- 23000140
TI  - Disconnection and reconnection: the morphological basis of (mal)adaptation to
      stress.
AB  - Maladaptive responses to stress and the associated hypersecretion of
      glucocorticoids cause psychopathologies ranging from hyperemotional states and
      mood dysfunction to cognitive impairments. Research in both humans and animal
      models has begun to identify morphological correlates of these functional
      changes. These include dendritic and synaptic reorganization, glial remodeling,
      and altered cell fate in cortical and subcortical structures. The emerging view
      is that stress induces a 'disconnection syndrome' whereby the transmission and
      integration of information that are critical for orchestrating appropriate
      physiological and behavioral responses are perturbed. High-resolution
      spatiotemporal mapping of the complete neural circuitry and identification of the
      cellular processes impacted by stress will help to advance discovery of
      strategies to reduce or reverse the burden of stress-related neuropsychiatric
      disorders.

PMID- 23000141
TI  - A transgenic mouse marking live replicating cells reveals in vivo transcriptional
      program of proliferation.
AB  - Most adult mammalian tissues are quiescent, with rare cell divisions serving to
      maintain homeostasis. At present, the isolation and study of replicating cells
      from their in vivo niche typically involves immunostaining for intracellular
      markers of proliferation, causing the loss of sensitive biological material. We
      describe a transgenic mouse strain, expressing a CyclinB1-GFP fusion reporter,
      that marks replicating cells in the S/G2/M phases of the cell cycle. Using flow
      cytometry, we isolate live replicating cells from the liver and compare their
      transcriptome to that of quiescent cells to reveal gene expression programs
      associated with cell proliferation in vivo. We find that replicating hepatocytes
      have reduced expression of genes characteristic of liver differentiation. This
      reporter system provides a powerful platform for gene expression and metabolic
      and functional studies of replicating cells in their in vivo niche.

PMID- 23000142
TI  - Kinesin-13 and tubulin posttranslational modifications regulate microtubule
      growth in axon regeneration.
AB  - The microtubule (MT) cytoskeleton of a mature axon is maintained in a stabilized
      steady state, yet after axonal injury it can be transformed into a dynamic
      structure capable of supporting axon regrowth. Using Caenorhabditis elegans
      mechanosensory axons and in vivo imaging, we find that, in mature axons, the
      growth of MTs is restricted in the steady state by the depolymerizing kinesin-13
      family member KLP-7. After axon injury, we observe a two-phase process of MT
      growth upregulation. First, the number of growing MTs increases at the injury
      site, concomitant with local downregulation of KLP-7. A second phase of
      persistent MT growth requires the cytosolic carboxypeptidase CCPP-6, which
      promotes Delta2 modification of alpha-tubulin. Both phases of MT growth are
      coordinated by the DLK-1 MAP kinase cascade. Our results define how the stable MT
      cytoskeleton of a mature neuron is converted into the dynamically growing MT
      cytoskeleton of a regrowing axon.

PMID- 23000143
TI  - A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual
      disability.
AB  - The discovery of mutations causing human disease has so far been biased toward
      protein-coding regions. Having excluded all annotated coding regions, we
      performed targeted massively parallel resequencing of the nonrepetitive genomic
      linkage interval at Xq28 of family MRX3. We identified in the binding site of
      transcription factor YY1 a regulatory mutation that leads to overexpression of
      the chromatin-associated transcriptional regulator HCFC1. When tested on
      embryonic murine neural stem cells and embryonic hippocampal neurons, HCFC1
      overexpression led to a significant increase of the production of astrocytes and
      a considerable reduction in neurite growth. Two other nonsynonymous, potentially
      deleterious changes have been identified by X-exome sequencing in individuals
      with intellectual disability, implicating HCFC1 in normal brain function.

PMID- 23000145
TI  - A hypermorphic missense mutation in PLCG2, encoding phospholipase Cgamma2, causes
      a dominantly inherited autoinflammatory disease with immunodeficiency.
AB  - Whole-exome sequencing was performed in a family affected by dominantly inherited
      inflammatory disease characterized by recurrent blistering skin lesions,
      bronchiolitis, arthralgia, ocular inflammation, enterocolitis, absence of
      autoantibodies, and mild immunodeficiency. Exome data from three samples,
      including the affected father and daughter and unaffected mother, were filtered
      for the exclusion of reported variants, along with benign variants, as determined
      by PolyPhen-2. A total of eight transcripts were identified as possible candidate
      genes. We confirmed a variant, c.2120C>A (p.Ser707Tyr), within PLCG2 as the only
      de novo variant that was present in two affected family members and not present
      in four unaffected members. PLCG2 encodes phospholipase Cgamma2 (PLCgamma2), an
      enzyme with a critical regulatory role in various immune and inflammatory
      pathways. The p.Ser707Tyr substitution is located in an autoinhibitory SH2 domain
      that is crucial for PLCgamma2 activation. Overexpression of the altered
      p.Ser707Tyr protein and ex vivo experiments using affected individuals'
      leukocytes showed clearly enhanced PLCgamma2 activity, suggesting increased
      intracellular signaling in the PLCgamma2-mediated pathway. Recently, our
      laboratory identified in individuals with cold-induced urticaria and immune
      dysregulation PLCG2 exon-skipping mutations resulting in protein products with
      constitutive phospholipase activity but with reduced intracellular signaling at
      physiological temperatures. In contrast, the p.Ser707Tyr substitution in
      PLCgamma2 causes a distinct inflammatory phenotype that is not provoked by cold
      temperatures and that has different end-organ involvement and increased
      intracellular signaling at physiological temperatures. Our results highlight the
      utility of exome-sequencing technology in finding causal mutations in nuclear
      families with dominantly inherited traits otherwise intractable by linkage
      analysis.

PMID- 23000146
TI  - Nonsense mutations in AAGAB cause punctate palmoplantar keratoderma type Buschke
      Fischer-Brauer.
AB  - Punctate palmoplantar keratodermas (PPKPs) are rare autosomal-dominant inherited
      skin diseases that are characterized by multiple hyperkeratotic plaques
      distributed on the palms and soles. To date, two different loci in chromosomal
      regions 15q22-15q24 and 8q24.13-8q24.21 have been reported. Pathogenic mutations,
      however, have yet to be identified. In order to elucidate the genetic cause of
      PPKP type Buschke-Fischer-Brauer (PPKP1), we performed exome sequencing in five
      affected individuals from three families, and we identified in chromosomal region
      15q22.33-q23 two heterozygous nonsense mutations-c.370C>T (p.Arg124(*)) and
      c.481C>T (p.Arg161(*))-in AAGAB in all affected individuals. Using immunoblot
      analysis, we showed that both mutations result in premature termination of
      translation and truncated protein products. Analyses of mRNA of affected
      individuals revealed that the disease allele is either not detectable or only
      detectable at low levels. To assess the consequences of the mutations in skin, we
      performed immunofluorescence analyses. Notably, the amount of granular staining
      in the keratinocytes of affected individuals was lower in the cytoplasm but
      higher around the nucleus than it was in the keratinocytes of control
      individuals. AAGAB encodes the alpha-and gamma-adaptin-binding protein p34 and
      might play a role in membrane traffic as a chaperone. The identification of
      mutations, along with the results from additional studies, defines the genetic
      basis of PPKP1 and provides evidence that AAGAB plays an important role in skin
      integrity.

PMID- 23000144
TI  - Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility
      loci for primary biliary cirrhosis in the Japanese population.
AB  - For the identification of susceptibility loci for primary biliary cirrhosis
      (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese
      individuals (487 PBC cases and 476 healthy controls) and in a subsequent
      replication study that included 1,402 other Japanese individuals (787 cases and
      615 controls). In addition to the most significant susceptibility region, human
      leukocyte antigen (HLA), we identified two significant susceptibility loci,
      TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p =
      2.84 * 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 * 10(-8) for
      rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of
      individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed
      significant associations (combined p = 3.66 * 10(-8), 3.66 * 10(-9), and 3.04 *
      10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with
      PBC (combined p = 1.11 * 10(-6) and 1.42 * 10(-7), respectively) in the Japanese
      population. These observations indicated the existence of ethnic differences in
      genetic susceptibility loci to PBC and the importance of TNF signaling and B cell
      differentiation for the development of PBC in individuals of European descent and
      Japanese individuals.

PMID- 23000147
TI  - Focal congenital lipoatrophy and vascular malformation: a mild form of inverse
      Klippel-Trenaunay syndrome?
AB  - A 2 year-and seven month-old male boy with vascular malformation and localized
      soft tissue hypotrophy is reported. Such presentation could represent the mildest
      end of the spectrum of 'inverse' Klippel-Trenaunay syndrome, a recently proposed
      disorder presenting with tissue hypotrophy as opposed to partial or complete limb
      overgrowth of classic Klippel-Trenaunay syndrome.

PMID- 23000148
TI  - Uterine papillary serous cancer: a review of the literature.
AB  - OBJECTIVE: Uterine papillary serous carcinoma (UPSC) represents a distinct
      subtype of endometrial cancer. UPSC is less common than endometrioid carcinoma
      (ECC) but accounts for a disproportionate number of uterine cancer related
      deaths. This article critically reviews the literature pertinent to the
      pathology, pathogenesis, diagnosis, management, and outcome of patients with
      UPSC. METHODS: MEDLINE was searched for all research articles published in
      English between January 1, 1967-January 1, 2012 which reported on patients
      diagnosed with UPSC. Given the rarity of this tumor, studies were not limited by
      design or number of reported patients. RESULTS: UPSC represents a histologically
      aggressive subtype of endometrial cancer. It commonly presents with extra uterine
      disease involvement which can be identified by comprehensive surgical staging.
      Optimal cytoreduction and systemic platinum/taxane-based adjuvant therapy appear
      to confer a survival advantage. CONCLUSIONS: UPSC is a biologically distinct
      entity, different from ECC. Future studies should explore the role of targeted
      therapies in the management of UPSC.

PMID- 23000149
TI  - Enkephalin surges in dorsal neostriatum as a signal to eat.
AB  - Compulsive overconsumption of reward characterizes disorders ranging from binge
      eating to drug addiction. Here, we provide evidence that enkephalin surges in an
      anteromedial quadrant of dorsal neostriatum contribute to generating intense
      consumption of palatable food. In ventral striatum, mu opioid circuitry
      contributes an important component of motivation to consume reward. In dorsal
      neostriatum, mu opioid receptors are concentrated within striosomes that receive
      inputs from limbic regions of prefrontal cortex. We employed advanced opioid
      microdialysis techniques that allow detection of extracellular enkephalin levels.
      Endogenous >150% enkephalin surges in anterior dorsomedial neostriatum were
      triggered as rats began to consume palatable chocolates. In contrast, dynorphin
      levels remained unchanged. Furthermore, a causal role for mu opioid stimulation
      in overconsumption was demonstrated by observations that microinjection in the
      same anterior dorsomedial quadrant of a mu receptor agonist ([D-Ala2, N-MePhe4,
      Gly-ol]-enkephalin; DAMGO) generated intense >250% increases in intake of
      palatable sweet food (without altering hedonic impact of sweet tastes). Mapping
      by "Fos plume" methods confirmed the hyperphagic effect to be anatomically
      localized to the anteromedial quadrant of the dorsal neostriatum, whereas other
      quadrants were relatively ineffective. These findings reveal that opioid signals
      in anteromedial dorsal neostriatum are able to code and cause motivation to
      consume sensory reward.

PMID- 23000150
TI  - Role of the Mad2 dimerization interface in the spindle assembly checkpoint
      independent of kinetochores.
AB  - BACKGROUND: The spindle assembly checkpoint (SAC) arrests cells when kinetochores
      are unattached to spindle microtubules. The signaling pathway is initiated at the
      kinetochores by one SAC component, Mad2, which catalyzes the initial steps of the
      cascade via the conformational dimerization of its open and closed conformers.
      Away from kinetochores, the dimerization surface of Mad2 has been proposed, based
      on data in vitro, to either interact with SAC activators or inactivators and thus
      to contribute to SAC activation or silencing. Here, we analyze its role in vivo.
      RESULTS: To analyze the putative pathway downstream of the kinetochores, we used
      two complementary approaches: we activated the SAC ectopically and independently
      from kinetochores, and we separated genetically the kinetochore-dependent and
      independent pools of Mad2. We found that the dimerization surface is required
      also downstream of kinetochores to mount a checkpoint response. CONCLUSION: Our
      results show that away from kinetochores the dimerization surface is required for
      stabilizing the end-product of the pathway, the mitotic checkpoint complex.
      Surprisingly, downstream of kinetochores the surface does not mediate Mad2
      dimerization. Instead, our results are consistent with a role of Mad3 as the main
      interactor of Mad2 via the dimerization surface.

PMID- 23000152
TI  - Recoverable Pd/C catalyst mediated dehydrogenation of sterols and an improved
      synthesis of 1alpha-hydroxydehydroepiandrosterone.
AB  - A novel recyclable Pd/C catalyst mediated dehydrogenation of sterols is
      developed. The conversion of sterols to 1,4,6-trien-3-ones is best achieved with
      Pd/C as a catalyst (10%) in the presence of six equivalents of allyl diethyl
      phosphate (ADP) and excess amount of sodium carbonate in DMF under vigorous
      reflux conditions. This transformation gives 17,17-ethylenedioxyandrost-1,4,6
      trien-3-one in better yield than that of DDQ oxidation and thus provides an
      improved synthesis of 1alpha-hydroxydehydroepiandrosterone from DHEA.

PMID- 23000151
TI  - Deep brain photoreceptors control light-seeking behavior in zebrafish larvae.
AB  - Most vertebrates process visual information using elaborately structured
      photosensory tissues, including the eyes and pineal. However, there is strong
      evidence that other tissues can detect and respond to photic stimuli. Many
      reports suggest that photosensitive elements exist within the brain itself and
      influence physiology and behavior; however, a long-standing puzzle has been the
      identity of the neurons and photoreceptor molecules involved. We tested whether
      light cues influence behavior in zebrafish larvae through deep brain
      photosensors. We found that larvae lacking eyes and pineal perform a simple light
      seeking behavior triggered by loss of illumination ("dark photokinesis").
      Neuroanatomical considerations prompted us to test orthopedia (otpa)-deficient
      fish, which show a profound reduction in dark photokinesis. Using targeted
      genetic ablations, we narrowed the photosensitive region to neurons in the
      preoptic area. Neurons in this region express several photoreceptive molecules,
      but expression of the melanopsin opn4a is selectively lost in otpa mutants,
      suggesting that opn4a mediates dark photokinesis. Our findings shed light on the
      identity and function of deep brain photoreceptors and suggest that otpa
      specifies an ancient population of sensory neurons that mediate behavioral
      responses to light.

PMID- 23000153
TI  - Increased medical costs in elders with the metabolic syndrome are most evident
      with hospitalization of men.
AB  - BACKGROUND: Little is known about health care costs associated with the metabolic
      syndrome (MetS). OBJECTIVE: We assessed annualized health care costs and health
      outcomes for both genders in different health care settings among representative
      Taiwanese elders. METHODS: The Nutrition and Health Survey in Taiwan (1999-2000)
      provided 1378 individuals aged 65 years or older with known MetS status.
      Nutrition and Health Survey in Taiwan files were linked to National Health
      Insurance records (1999-2006). Student t tests and multiple regression models
      were used to assess expenditures in total and in 6 services: inpatient,
      ambulatory care, dental care, traditional Chinese medicine, emergency care, and
      contracted pharmacy. The Cox model was used to assess gender effect on all-cause
      mortality and cardiovascular disease mortality, whereas logistic regression was
      used for that on cardiovascular disease hospitalization. The 5 MetS component
      costs were evaluated by multiple regressions. RESULTS: MetS affected 29% of men
      and 48% of women. After full adjustment, those with MetS had 1.30 (95% CI, 1.11
      1.52), men had 1.43 (95% CI, 1.20-1.70), and women had 1.19 (95% CI, 0.93-1.52)
      times higher costs than those without MetS. Compared with no MetS, MetS costs
      were increased 2.94-fold for inpatient care (95% CI, 1.23-7.10) and 1.30-fold for
      ambulatory care for men (95% CI, 1.12-1.52), whereas ambulatory MetS costs were
      increased 1.28-fold for women (95% CI, 1.05-1.57). MetS was associated with
      higher risk of cardiovascular disease hospitalization in men (adjusted odds
      ratio, 1.76; 95% CI, 1.20-2.58) but not in women (adjusted odds ratio, 1.08; 95%
      CI, 0.67-1.75). Among those with MetS, all-cause and cardiovascular mortality
      were comparable between men and women. Of the MetS components, low HDL
      cholesterol had the greatest affect on costs, more so in men (2.23-fold) than
      women (1.58-fold). CONCLUSIONS: In people with MetS, service costs were greater
      overall, significantly for men, but not women, and these increased costs were
      evident for men who experienced hospitalization, but not women. At the same time,
      cardiovascular and all-cause mortalities were not significantly different by
      gender in regard to MetS in Taiwanese elders.

PMID- 23000154
TI  - Contracting cardiomyocytes in hydrophobic room-temperature ionic liquid.
AB  - Room-temperature ionic liquids (RTILs) are drawing attention as a new class of
      nonaqueous solvents to replace organic and aqueous solvents for chemical
      processes in the liquid phase at room temperature. The RTILs are notable for
      their characteristics of nonvolatility, extremely low vapor pressure, electric
      conductivity, and incombustibility. These distinguished properties of RTILs have
      brought attention to them in applications with biological cells and tissue in
      vacuum environment for scanning electron microscopy, and in microfluidic devices
      for micro-total analysis system (micro-TAS). Habitable RTILs could increase
      capability of nonaqueous micro-TAS for living cells. Some RTILs seemed to have
      the capability to replace water in biological applications. However, these RTILs
      had been applied to just supplemental additives for biocompatible test, to fixed
      cells as a substitute for an aqueous solution, and to simple molecules. None of
      RTILs in which directly soaks a living cell culture. Therefore, we demonstrated
      the design of RTILs for a living cell culture and a liquid electrolyte to
      stimulate contracting cardiomyocytes using the RTILs. We assessed the effect of
      RTILs on the cardiomyocytes using the beating lifetime to compare the
      applicability of RTILs for biological applications. Frequent spontaneous
      contractions of cardiomyocytes were confirmed in amino acid anion RTILs
      [P(8,8,8,8)][Leu] and [P(8,8,8,8)][Ala], phosphoric acid derivatives
      [P(8,8,8,8)][MeO(H)PO(2)], and [P(8,8,8,8)][C(7)CO(2)]. The anion type of RTILs
      had influence on applicable characteristics for the contracting cardiomyocyte.
      This result suggested the possibility for biocompatible design of hydrophobic
      group RTILs to achieve biological applications with living cells.

PMID- 23000155
TI  - Role of the Na(+)/H(+) exchanger on the development of diabetes mellitus and its
      chronic complications.
AB  - Micro- and macrovascular complications are the main cause of morbidity and
      mortality in diabetes mellitus. The Na(+)/H(+) exchanger (NHE) is a family of
      proteins which exchange Na(+) for H(+) according to their concentration gradients
      in an electroneutral manner. The exchanger also plays a key role in several other
      cellular functions including proliferation, differentiation, apoptosis,
      migration, and cytoskeletal organization. Since not much is known on the
      relationship between NHE and diabetes mellitus, this review outlines the
      contribution of NHE to chronic complications of diabetes mellitus, such as
      diabetic nephropathy; diabetic cardiomyopathy.

PMID- 23000156
TI  - Ternatin, a cyclic peptide isolated from mushroom, and its derivative suppress
      hyperglycemia and hepatic fatty acid synthesis in spontaneously diabetic KK-A(y)
      mice.
AB  - (-)-Ternatin is a highly methylated cyclic heptapeptide isolated from mushroom
      Coriolus versicolor. Ternatin has an inhibitory effect on fat accumulation in 3T3
      L1 adipocytes. [D-Leu(7)]ternatin, a ternatin derivative, also inhibited fat
      accumulation in 3T3-L1 cells, although the effectiveness of [D-Leu(7)]ternatin
      was lower than that of ternatin. In this study, we investigated the effects of
      ternatin and [D-Leu(7)]ternatin on obesity and type 2 diabetes in KK-A(y) mice,
      an animal model for spontaneously developed type 2 diabetes. We continuously
      administered ternatin (8.5 or 17 nmol/day) or [D-Leu(7)]ternatin (68 nmol/day) to
      mice via a subcutaneous osmotic pump. Unexpectedly, neither ternatin nor [D
      Leu(7)]ternatin affected body weight or adipose tissue weight in KK-A(y) mice. In
      contrast, it was demonstrated that both ternatin and [D-Leu(7)]ternatin suppress
      the development of hyperglycemia. In liver, the SREBP-1c mRNA level tended to be
      lower or significantly decreased in mice treated with ternatin or [D
      Leu(7)]ternatin, respectively. Moreover, we found that ternatin directly lowered
      the SREBP-1c mRNA level in Hepa1-6 hepatocyte cells. This study showed that
      ternatin and [D-Leu(7)]ternatin each had a preventive effect on hyperglycemia and
      a suppressive effect on fatty acid synthesis in KK-A(y) mice.

PMID- 23000157
TI  - Matrigel basement membrane matrix influences expression of microRNAs in cancer
      cell lines.
AB  - Matrigel is a medium rich in extracellular matrix (ECM) components used for three
      dimensional cell culture and is known to alter cellular phenotypes and gene
      expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene
      expression and have roles in cancer. While miRNA profiles of numerous cell lines
      cultured on plastic have been reported, the influence of Matrigel-based culture
      on cancer cell miRNA expression is largely unknown. This study investigated the
      influence of Matrigel on the expression of miRNAs that might facilitate ECM
      associated cancer cell growth. We performed miRNA profiling by microarray using
      two colon cancer cell lines (SW480 and SW620), identifying significant
      differential expression of miRNAs between cells cultured in Matrigel and on
      plastic. Many of these miRNAs have previously been implicated in cancer-related
      processes. A common Matrigel-induced miRNA signature comprised of up-regulated
      miR-1290 and miR-210 and down-regulated miR-29b and miR-32 was identified using
      RT-qPCR across five epithelial cancer cell lines (SW480, SW620, HT-29, A549 and
      MDA-MB-231). Experimental modulation of these miRNAs altered expression of their
      known target mRNAs involved in cell adhesion, proliferation and invasion, in
      colon cancer cell lines. Furthermore, ITGA5 was identified as a novel putative
      target of miR-32 that may facilitate cancer cell interactions with the ECM. We
      propose that culture of cancer cell lines in Matrigel more accurately
      recapitulates miRNA expression and function in cancer than culture on plastic and
      thus is a valuable approach to the in vitro study of miRNAs.

PMID- 23000158
TI  - Ectopic expression of ubiquitin-conjugating enzyme gene from wild rice, OgUBC1,
      confers resistance against UV-B radiation and Botrytis infection in Arabidopsis
      thaliana.
AB  - A previously unidentified gene encoding ubiquitin-conjugating enzyme was isolated
      from leaves of wild rice plant treated with wounding and microbe-associated
      molecular patterns. The OgUBC1 gene was composed of 148 amino acids and contained
      a typical active site and 21 ubiquitin thioester intermediate interaction
      residues and 4 E3 interaction residues. Both exogenous application of salicylic
      acid and UV-B irradiation triggered expression of OgUBC1 in leaves of wild rice.
      Recombinant OgUBC1 proteins bound to ubiquitins in vitro, proposing that the
      protein might act as E2 enzyme in planta. Heterologous expression of the OgUBC1
      in Arabidopsis thaliana protected plants from cellular damage caused by an excess
      of UV-B radiation. A stable expression of chalcone synthase gene was detected in
      leaves of OgUBC1-expressing Arabidopsis, resulting in producing higher amounts of
      anthocyanin than those in wild-type Col-0 plants. Additionally, both pathogenesis
      related gene1 and 5 were transcribed in the transgenic Arabidopsis in the absence
      of pathogen infection. The OgUBC1-expressing plants were resistant to the
      infection of Botrytis cinerea. Taken together, we suggested that the OgUBC1 is
      involved in ubiquitination process important for cellular response against biotic
      and abiotic stresses in plants.

PMID- 23000159
TI  - Estrogen receptor beta interacts and colocalizes with HADHB in mitochondria.
AB  - Estrogen receptors are localized in mitochondria, but their functions in this
      organelle remain unclear. We previously found that ERalpha interacted with
      mitochondrial protein HADHB and affected the thiolytic cleavage activity of HADHB
      in beta-oxidation. It is known that ERbeta binds to ERalpha. In addition, ERbeta
      is predominately located in mitochondria. These facts led us to speculate that
      ERbeta may also be associated with HADHB in mitochondria. In order to test this
      hypothesis, we performed co-immunoprecipitation and confocal microscopy analyses
      with human breast cancer MCF7 cells. The results demonstrated that ERbeta was
      indeed associated and colocalized with HADHB within mitochondria. Interestingly,
      in contrast to the stimulatory effect of ERalpha on HADHB enzyme activity
      observed in the previous study, silencing of ERbeta enhanced the enzyme activity
      of HADHB in the present study, suggesting that ERbeta plays an inhibitory role in
      HADHB enzyme activity in the breast cancer cells. Our results imply that ERalpha
      and ERbeta may differentially affect cellular oxidative stress through
      influencing the rate of beta-oxidation of fatty acids in breast cancer cells.

PMID- 23000160
TI  - Letter to the editor on "Effects of BMP-2 and vitamin D3 on the osteogenic
      differentiation of adipose stem cells".

PMID- 23000161
TI  - Influence of apolipoprotein A-V on hepatocyte lipid droplet formation.
AB  - Apolipoprotein A-V (apoA-V) is postulated to modulate intra-hepatic triglyceride
      (TG) trafficking. Stably transfected McA-RH7777 hepatocarcinoma cells expressing
      human apoA-V displayed enhanced neutral lipid staining while conditioned media
      from these cells had 40+/-8% less TG than cells transfected with a control
      vector. To obtain homogeneous cell lines expressing different amounts of apoA-V,
      a strategy of clonal selection was pursued. Immunoblot analysis of two distinct
      apoA-V stable cell lines yielded one that expresses low amounts of apoA-V and
      another that expresses higher amounts. Confocal fluorescence microscopy of
      control cells and cells expressing low levels of apoA-V had similar numbers of
      lipid droplets while cells expressing higher amounts of apoA-V had twice as many
      lipid droplets, on average. Thus, apoA-V expression promotes lipid droplet
      accumulation in these cells.

PMID- 23000162
TI  - A high resolution electro-optical approach for investigating transition of
      soluble proteins to integral membrane proteins probed by colicin A.
AB  - The transition from water soluble state to an integral membrane protein state is
      a crucial step in the formation of the active form of many pore-forming or
      receptor proteins. Albeit this, high resolution techniques which allow assay of
      protein membrane binding and concomitant development of the final active form in
      the membrane await further development. Here, we describe a horizontal artificial
      bilayers setup allowing for simultaneous electrical and optical measurements at a
      single molecule level. We use the membrane binding and subsequent channel
      formation of colicin A (ColA) a water soluble bacteriocin secreted by some
      strains of Escherichia coli to demonstrate the potential of the combined electro
      optical technique. Our results expand the knowledge on ColA molecular details
      which show that active ColA is monomeric; membrane binding is pH but not membrane
      potential (Deltaphi) dependent. ColA is at Deltaphi=0 permeable for molecules >=1
      nm. Although ColA exhibits low ion conductance it facilitates permeation of large
      molecules. Our electro-optical recordings reveal ColA monomeric state and the
      chimeric character of its pore.

PMID- 23000163
TI  - The histone demethylase LSD1 is required for estrogen-dependent S100A7 gene
      expression in human breast cancer cells.
AB  - S100A7, a member of S100 calcium binding protein family, is highly associated
      with breast cancer. However, the molecular mechanism of S100A7 regulation remains
      unclear. Here we show that long-term treatment with estradiol stimulated S100A7
      expression in MCF7 breast cancer cells at both the transcriptional and
      translational levels. Both treatment with a histone demethylase LSD1 inhibitor
      and shRNA-based knockdown of LSD1 expression significantly decreased 17beta
      estradiol (E2)-induced S100A7 expression. These reduced E2-mediated S100A7
      expression are rescued by the overexpressed wild-type LSD1 but not by its
      catalytically inactive mutant. Our data showed in vivo association of LSD1 with
      S100A7 promoters, confirming the potential role of LSD1 in regulating S100A7
      expression. S100A7 knockdown increased both normal cell growth and estrogen
      induced cell proliferation, suggesting a negative influence by S100A7 on the
      growth of cancer cells. Together, our data suggest that estrogen-induced S100A7
      expression mediated by the histone demethylase LSD1 may downregulate breast
      cancer cell proliferation, implying a potential tumor suppressor-like function
      for S100A7.

PMID- 23000164
TI  - Overexpression of gma-MIR394a confers tolerance to drought in transgenic
      Arabidopsis thaliana.
AB  - MicroRNAs, key posttranscriptional regulators of eukaryotic gene expression, play
      important roles in plant development and response to stress. In this study, a
      soybean gma-MIR394a gene was functionally characterized, especially with regard
      to its role in drought stress resistance. Expression analysis revealed that gma
      MIR394a was expressed differentially in various soybean tissues and was induced
      by drought, high salinity, low temperature stress, and abscisic acid treatment in
      leaves. One target gene of gma-miR394a, Glyma08g11030, was predicted and verified
      using a modified 5' RLM-RACE (RNA ligase-mediated rapid amplification of 5' cDNA
      ends) assay. Overexpression of gma-MIR394a resulted in plants with lowered leaf
      water loss and enhanced drought tolerance. Furthermore, overexpression of gma
      MIR394a in Arabidopsis reduced the transcript of an F-box gene (At1g27340)
      containing a miR394 complementary target site. These results suggest that the gma
      MIR394a gene functions in positive modulation of drought stress tolerance and has
      potential applications in molecular breeding to enhance drought tolerance in
      crops.

PMID- 23000165
TI  - Regulation of OCT4 gene expression by liver receptor homolog-1 in human embryonic
      carcinoma cells.
AB  - We demonstrate the regulation of OCT4 gene expression mediated by liver receptor
      homolog-1 (LRH-1) in human embryonic carcinoma cells. LRH-1 and OCT4 are co
      expressed in undifferentiated NCCIT cells and decreased during retinoic acid
      induced differentiation. Dose-dependent overexpression of LRH-1 transactivated
      the OCT4 promoter activity and its dominant negative form with a deletion of
      activation function-2 motif reduced the activity even in the presence of LRH-1.
      The OCT4 promoter contains potent three LRH-1 binding sites; one within conserved
      region (CR) 1 and two within CR2. Mutagenesis of each binding site affected the
      decrease in OCT4 promoter activity and the 2nd binding site mutant most
      significantly reduced the transcriptional activity, compared to that of 1st and
      3rd binding site mutants, respectively. Simultaneous disruption of 2nd and 3rd
      binding sites led to significant down-regulation of the activity even in the
      presence of 1st binding site-containing CR1. Moreover, mutation of each binding
      element within native or exogenous minimal promoter-driven CR1 or CR2 also
      decreased the promoter activity to some different extent, suggesting that three
      binding elements may be implicated in the induction of the full-activity of OCT4
      promoter. In vivo binding assay revealed the 2nd and 3rd binding motifs within
      CR2 were more enriched than the 1st one within CR1. Taken together, our study
      indicates that LRH-1 acts as a transcriptional activator in the regulation of
      OCT4 gene expression through the cooperative interaction with three binding sites
      directly or/and indirectly.

PMID- 23000166
TI  - Development of mice without Cip/Kip CDK inhibitors.
AB  - Timely exit of cells from the cell cycle is essential for proper cell
      differentiation during embryogenesis. Cyclin-dependent kinase (CDK) inhibitors
      (CKIs) of the Cip/Kip family (p21, p27, and p57) are negative regulators of cell
      cycle progression and are thought to be essential for development. However, the
      extent of functional redundancy among Cip/Kip family members has remained largely
      unknown. We have now generated mice that lack all three Cip/Kip CKIs (TKO mice)
      and compared them with those lacking each possible pair of these proteins (DKO
      mice). We found that the TKO embryos develop normally until midgestation but die
      around embryonic day (E) 13.5, slightly earlier than p27/p57 DKO embryos. The TKO
      embryos manifested morphological abnormalities as well as increased rates of cell
      proliferation and apoptosis in the placenta and lens that were essentially
      indistinguishable from those of p27/p57 DKO mice. Unexpectedly, the proliferation
      rate and cell cycle profile of mouse embryonic fibroblasts (MEFs) lacking all
      three Cip/Kip CKIs did not differ substantially from those of control MEFs. The
      abundance and kinase activity of CDK2 were markedly increased, whereas CDK4
      activity and cyclin D1 abundance were decreased, in both p27/p57 DKO and TKO MEFs
      during progression from G(0) to S phase compared with those in control MEFs. The
      extents of the increase in CDK2 activity and the decrease in CDK4 activity and
      cyclin D1 abundance were greater in TKO MEFs than in p27/p57 DKO MEFs. These
      results suggest that p27 and p57 play an essential role in mouse development
      after midgestation, and that p21 plays only an auxiliary role in normal
      development (although it is thought to be a key player in the response to DNA
      damage).

PMID- 23000167
TI  - The essential oil of Croton zehntneri and trans-anethole improves cutaneous wound
      healing.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Croton zehntneri is a Euphorbiaceae species native
      to northeastern Brazil, where teas and beverages made from Croton zehntneri
      leaves are used as healing agents. To our knowledge, there is no experimental
      study supporting this claim of pharmacological activity. MATERIALS AND METHODS:
      Full-thickness excisional wounds were made in the left and right sides of the
      dorsum of anesthetised Swiss mice, and a topical pharmaceutical formulation,
      developed by including essential oil extracted from the leaves of Croton
      zehntneri (2% and 20% EOCz) in pluronic-127 (PF-127), was administered to mice
      twice daily for 15 days post-wounding. To evaluate the contribution of trans
      anethole, the major constituent of EOCz (85.7%), in the wound healing activity of
      EOCz, the effect of the topical administration of trans-AT on wound tissue repair
      was also evaluated and compared to other groups. A macroscopic analysis of
      swelling and exudates was performed and scored as 0 (missing), 1 (light), 2
      (moderate) and 3 (intense). The number of capillaries and leukocytes was counted
      in hematoxylin and eosin (HE)-stained sections of the injured tissue. For
      extracellular matrix remodelling analysis, fibroblasts and collagen fibres
      present in the photomicrography of the Masson's Trichrome (MT)-stained sections
      were counted. Each experimental group comprised six mice. RESULTS: At day 3 post
      wounding, it was observed that treatment with 20% EOCz greatly reduced the
      swelling and exudates with a similar magnitude to the dexamethasone treatment.
      The inflammatory cell infiltration and angiogenesis were not altered by either
      the EOCz- or trans-AT treatments. In contrast, an acceleration of the wound
      closure was observed, with an enhanced number of fibroblasts and collagen fibres
      in both the 20% EOCz- and trans-AT-treated mice. CONCLUSION: Our data indicate
      that EOCz exerts significant wound healing activity, demonstrating its relevant
      therapeutic potential.

PMID- 23000168
TI  - Chemical characteristics and antimicrobial effects of some Eucalyptus kinos.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus kinos are tannin-rich, mostly red
      coloured wood exudates. They have played an important role in the traditional
      medicines of Australian Aboriginal people and were also a valued source of
      antibacterial and astringent agents for early European settlers. MATERIALS AND
      METHODS: Nineteen different Eucalyptus kinos were collected and analysed for
      their total phenolics and total tannin content as well as their relative amounts
      of hydrolysable and condensed tannins. They were also classified in accordance
      with Maiden's traditional kino categories. Well plate diffusion assays using
      three Gram positive and two Gram negative bacteria and a yeast species were
      carried out to assess antimicrobial properties. RESULTS: The investigated kino
      samples differ strongly in their total phenolics and overall tannin as well as
      their relative hydrolysable and condensed tannin contents. All but one could be
      assigned to one of the traditional Maiden kino classes. The samples, in
      particular those collected from Corymbia maculata and Eucalyptus ficifolia,
      demonstrated a strong antibacterial activity towards Gram positive bacteria but
      were inactive against the Gram negative strains and the yeast. No obvious
      correlation seems to exist between a particular Maiden class and antibacterial
      activity but there is a positive correlation between total phenolics/tannin
      content and antibacterial effect although two of the investigated kinos
      (Eucalyptus flocktoniae and Eucalyptus sargentii) deviated from this trend. The
      relative amounts of hydrolysable and condensed tannins in a kino sample do not
      seem to determine the antibacterial effect. CONCLUSION: Eucalpytus kinos present
      an interesting class of natural products which should be investigated further,
      not only to contribute to the growing field of tannin chemistry but to also learn
      more about the individual role played by the various hydrolysable and condensed
      tannins that determine a kino's antibacterial activity and to contribute to a
      better understanding of the use of some of these kinos in traditional systems of
      medicine. In particular samples like Eucalyptus flocktoniae kino, which recorded
      a higher antibacterial activity than predicted based on total tannin content,
      warrant more detailed chemical and antimicrobial analyses.

PMID- 23000169
TI  - Cell cycle arrest and cell apoptosis induced by Equisetum hyemale extract in
      murine leukemia L1210 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Equisetum hyemale has been used as a traditional
      herbal medicine to treat various diseases such as hypertension, inflammatory
      diseases, acute stroke, bleeding and cancer. The present study aimed to
      investigate the anti-proliferative effect and the underlying mechanisms of
      E.hyemale extract on murine leukemia L1210 cells. MATERIALS AND METHODS: The
      inhibitory effect of Ehyemale extract on L1210cells was evaluated by MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle
      distribution was evaluated with flow cytometry following PI (propidium iodide)
      staining. Apoptotic cell death was determined by Annexin V-FITC/PI and nuclear
      DAPI (4'-6-diamidino-2-phenylindole) staining. DNA damage and changes of
      mitochondrial membrane potential were also detected with flow cytometry analysis.
      RESULTS: E.hyemale extract exerted significant antiproliferative effects on L1210
      cells in a dose- and time-dependent manner. Flow cytometry analysis showed that
      E.hyemale extract induced cell cycle arrest at G2/M phase in L1210 cells.
      Phosphatidylserine exposure, chromatin condensation, DNA damage and loss of
      mitochondrial membrane potential were observed clearly after treatment with
      Ehyemale extract. CONCLUSION: The results in this study indicate that E.hyemale
      extract could inhibit L1210 cell proliferation through inducing G2/M arrest and
      cell apoptosis.

PMID- 23000170
TI  - Ethnoveterinary knowledge and practices at Colares Island, Para state, eastern
      Amazon, Brazil.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The lack of ethnoveterinary surveys in Brazil,
      especially in the Amazon region, results in losses in the veterinary
      phytopharmacology field and in scientific documentation of the cultural
      traditions of plant use in the treatment of animal diseases. AIM OF THE STUDY: To
      catalog, analyze and disseminate the ethnoveterinary knowledge of the inhabitants
      of Colares Island, Para state, eastern Amazon, Brazil. MATERIALS AND METHODS: A
      total of 72 interviews were conducted, and semi-structured questionnaires were
      answered by 18 men and 54 women. The data obtained were quantitatively analyzed
      using the informant consensus factor (ICF) and use value (UV). The plants with a
      reported medicinal use for domestic animals were harvested, herbalized and
      botanically identified. RESULTS: Fifty-six plants, distributed in 49 genera and
      35 families, were indicated to have 23 different medicinal uses, divided into six
      categories of use. The highest ICF (0.80) was obtained for the antiparasitic
      class. The Euphorbiaceae family exhibited the highest number of citations, and
      the species with the highest UVs were Caladium cf. bicolor, Bixa orellana, Carapa
      guianensis, Jatropha curcas and Cymbopogon citratus. The parts of the 56 plants
      that were most frequently used to prepare ethnoveterinary medications were the
      leaves (46%), bark (15%), roots and fruit (10%). The use of the macerated leaves
      was the most common method of application, used by 43% of the interviewees, and
      the majority of the preparations (87.3%) used a single plant. In addition to
      medicinal plants, the interviewees reported the use of products of animal and
      mineral origin. CONCLUSION: The present study contributed to the establishment of
      an inventory of plants used in ethnoveterinary practices in this region of the
      Brazilian eastern Amazon. Future phytochemical and pharmacological studies are
      needed to confirm the efficacy and safety of the identified plants, enabling
      communities to use them in a more economic, effective and safe manner.

PMID- 23000171
TI  - The prevalence of mental disorders in older people in Western countries - a meta
      analysis.
AB  - OBJECTIVE: To conduct a meta-analysis assessing the prevalence of mental
      disorders in older people in Europe and North America. METHOD: Studies that
      reported prevalence rates of mental disorders in older people from the general
      population were identified through MEDLINE, PsycINFO, Web of Science, and
      reference lists for the period between January 2000 and December 2011. Studies
      were included if they reported prevalence rates of mental disorders in older
      people (50+ years) from the community. The final sample comprised 25 studies.
      Prevalence rates were extracted, and effect sizes were transformed into logits.
      Random-effects models were calculated due to significant heterogeneity. In meta
      regression analyses possible sources of bias, including age of onset, gender
      distribution, and risk of bias were examined. To analyze the robustness of the
      results, sensitivity analyses were performed. Publication bias was assessed with
      funnel plots and the Egger method. RESULTS: Disorders with the highest prevalence
      estimates were dimensional depression (19.47%), lifetime major depression
      (16.52%), and lifetime alcohol use disorders (11.71%). Disorders with the lowest
      estimates were current and lifetime drug use disorders (0.34% and 0.19%,
      respectively), and current bipolar disorder and current agoraphobia (both 0.53%).
      CONCLUSION: The majority of studies investigated major depression, panic disorder
      and social phobia. Future research requires a larger database on the epidemiology
      of mental disorders in the elderly. Furthermore, an improvement to the
      methodology that addresses the challenges of older age and produces comparable
      data, including the use of instruments tailored to the needs of older people, is
      required.

PMID- 23000172
TI  - Transcriptome-wide analysis of exosome targets.
AB  - The exosome plays major roles in RNA processing and surveillance but the in vivo
      target range and substrate acquisition mechanisms remain unclear. Here we apply
      in vivo RNA crosslinking (CRAC) to the nucleases (Rrp44, Rrp6), two structural
      subunits (Rrp41, Csl4) and a cofactor (Trf4) of the yeast exosome. Analysis of
      wild-type Rrp44 and catalytic mutants showed that both the CUT and SUT classes of
      non-coding RNA, snoRNAs and, most prominently, pre-tRNAs and other Pol III
      transcripts are targeted for oligoadenylation and exosome degradation. Unspliced
      pre-mRNAs were also identified as targets for Rrp44 and Rrp6. CRAC performed
      using cleavable proteins (split-CRAC) revealed that Rrp44 endonuclease and
      exonuclease activities cooperate on most substrates. Mapping oligoadenylated
      reads suggests that the endonuclease activity may release stalled exosome
      substrates. Rrp6 was preferentially associated with structured targets, which
      frequently did not associate with the core exosome indicating that substrates
      follow multiple pathways to the nucleases.

PMID- 23000173
TI  - Signal-induced disassembly of the SCF ubiquitin ligase complex by Cdc48/p97.
AB  - A large group of E3 ubiquitin ligases is formed by the multisubunit SCF complex,
      whose core complex (Rbx1/Cul1-Cdc53/Skp1) binds one of many substrate recruiting
      F-box proteins to form an array of SCF ligases with diverse substrate
      specificities. It has long been thought that ubiquitylation by SCF ligases is
      regulated at the level of substrate binding. Here we describe an alternative
      mechanism of SCF regulation by active dissociation of the F-box subunit. We show
      that cadmium stress induces selective recruitment of the AAA(+) ATPase Cdc48/p97
      to catalyze dissociation of the F-box subunit from the yeast SCF(Met30) ligase to
      block substrate ubiquitylation and trigger downstream events. Our results not
      only provide an additional layer of ubiquitin ligase regulation but also suggest
      that targeted, signal-dependent dissociation of multisubunit enzyme complexes is
      an important mechanism in control of enzyme function.

PMID- 23000174
TI  - The membrane stress response buffers lethal effects of lipid disequilibrium by
      reprogramming the protein homeostasis network.
AB  - Lipid composition can differ widely among organelles and even between leaflets of
      a membrane. Lipid homeostasis is critical because disequilibrium can have disease
      outcomes. Despite their importance, mechanisms maintaining lipid homeostasis
      remain poorly understood. Here, we establish a model system to study the global
      effects of lipid imbalance. Quantitative lipid profiling was integral to monitor
      changes to lipid composition and for system validation. Applying global
      transcriptional and proteomic analyses, a dramatically altered biochemical
      landscape was revealed from adaptive cells. The resulting composite regulation we
      term the "membrane stress response" (MSR) confers compensation, not through
      restoration of lipid composition, but by remodeling the protein homeostasis
      network. To validate its physiological significance, we analyzed the unfolded
      protein response (UPR), one facet of the MSR and a key regulator of protein
      homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality
      control, and membrane integrity-functions otherwise lethally compromised in lipid
      dysregulated cells.

PMID- 23000175
TI  - DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility
      require TAp63-mediated induction of Puma and Noxa.
AB  - Trp63, a transcription factor related to the tumor suppressor p53, is activated
      by diverse stimuli and can initiate a range of cellular responses. TAp63 is the
      predominant Trp53 family member in primordial follicle oocyte nuclei and is
      essential for their apoptosis triggered by DNA damage in vivo. After gamma
      irradiation, induction of the proapoptotic BH3-only members Puma and Noxa was
      observed in primordial follicle oocytes from WT and Trp53(-/-) mice but not in
      those from TAp63-deficient mice. Primordial follicle oocytes from mice lacking
      Puma or both Puma and Noxa were protected from gamma-irradiation-induced
      apoptosis and, remarkably, could produce healthy offspring. Hence, PUMA and NOXA
      are critical for DNA damage-induced, TAp63-mediated primordial follicle oocyte
      apoptosis. Thus, blockade of PUMA may protect fertility during cancer therapy and
      prevent premature menopause, improving women's health.

PMID- 23000177
TI  - Improved preclinical cardiovascular therapeutic indices with long-term inhibition
      of norepinephrine reuptake using reboxetine.
AB  - Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE)
      levels, but therapeutic antidepressant activity is only observed after weeks of
      treatment because central NE levels progressively increase during continued drug
      exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart
      rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment
      changes the responsiveness of the central noradrenergic system and suppresses
      these effects via autonomic regulation. To better understand the relationship
      between NE increases and cardiovascular safety, we investigated acute and chronic
      effects of the NRI reboxetine on central NE release and on BP and HR and
      electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE
      release was assessed by microdialysis in medial prefrontal cortex (mPFC) and
      hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry.
      Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via
      an osmotic minipump and then challenged with acute intravenous doses of
      reboxetine. Animals chronically treated with reboxetine had 2-fold higher
      extracellular basal NE levels in mPFC and PVN compared to basal levels after
      chronic vehicle treatment. BP was significantly increased after the first day of
      treatment, and gradually returned to vehicle levels by day 21. These data
      indicate that chronic NRI treatment may lead to an increase in central NE levels
      and a concomitant reduction in BP based on exposure-response curves compared to
      vehicle treatment, suggesting a larger separation between preclinical estimates
      of efficacy vs. safety compared to acute NRI treatment.

PMID- 23000176
TI  - Extensive degradation of RNA precursors by the exosome in wild-type cells.
AB  - The exosome is a complex involved in the maturation of rRNA and sn-snoRNA, in the
      degradation of short-lived noncoding RNAs, and in the quality control of RNAs
      produced in mutants. It contains two catalytic subunits, Rrp6p and Dis3p, whose
      specific functions are not fully understood. We analyzed the transcriptome of
      combinations of Rrp6p and Dis3p catalytic mutants by high-resolution tiling
      arrays. We show that Dis3p and Rrp6p have both overlapping and specific roles in
      degrading distinct classes of substrates. We found that transcripts derived from
      more than half of intron-containing genes are degraded before splicing.
      Surprisingly, we also show that the exosome degrades large amounts of tRNA
      precursors despite the absence of processing defects. These results underscore
      the notion that large amounts of RNAs produced in wild-type cells are discarded
      before entering functional pathways and suggest that kinetic competition with
      degradation proofreads the efficiency and accuracy of processing.

PMID- 23000178
TI  - Common CTA features of Ebstein anomaly in a middle-aged woman with a heart murmur
      and dyspnea on exertion.
AB  - Ebstein anomaly is a rare and complex congenital heart defect that may present
      with a variety of clinical symptoms. This article presents the case of a 45-year
      old woman who presented with a history of a heart murmur and progressively
      worsening dyspnea on exertion. We describe the imaging features and protocol used
      for visualizing the congenital defect on a 256-channel multidetector CT scanner.

PMID- 23000179
TI  - Geometrical and topological measures for hydrodynamic dispersion in confined
      sphere packings at low column-to-particle diameter ratios.
AB  - At low column-to-particle diameter (or aspect) ratio (d(c)/d(p)) the kinetic
      column performance is dominated by the transcolumn disorder that arises from the
      morphological gradient between the more homogeneous, looser packed wall region
      and the random, dense core. For a systematic analysis of this morphology
      dispersion relation we computer-generated a set of confined sphere packings
      varying three parameters: aspect ratio (d(c)/d(p)=10-30), bed porosity (E=0.40
      0.46), and packing homogeneity. Plate height curves were received from simulation
      of hydrodynamic dispersion in the packings over a wide range of reduced
      velocities (v=0.5-500). Geometrical measures derived from radial porosity and
      velocity profiles were insufficient as morphological descriptors of the plate
      height data. After Voronoi tessellation of the packings, topological information
      was obtained from the statistical moments of the free Voronoi volume (V(free))
      distributions. The radial profile of the standard deviation of the V(free)
      distributions in the form of an integral measure was identified as a quantitative
      scalar measure for the transcolumn disorder. The first morphology-dispersion
      correlation for confined sphere packings deepens our understanding of how the
      packing microstructure determines the kinetic column performance.

PMID- 23000180
TI  - Method development and validation for the determination of 2,4,6-tribromoanisole,
      2,4,6-tribromophenol, 2,4,6-trichloroanisole, and 2,4,6-trichlorophenol in
      various drug products using stir bar sorptive extraction and gas chromatography
      tandem mass spectrometry detection.
AB  - Recently, haloanisoles and halophenols are associated with multiple product
      recall situations in the pharmaceutical industry. The majority of the recalls are
      associated with consumer complaints due to the presence of 2,4,6-tribromoanisole,
      as extremely low levels of this component can be easily detected by the human
      nose. As part of the root cause analysis to address the cause of the consumer
      complaints, a GC-MS/MS based analytical method combined with stir bar sorptive
      extraction (SBSE) sample preparation was developed for determination of
      halophenols and haloanisoles from various drug product formulations. The method
      also applies to the analysis of 2,4,6-tribromoanisole analysis in various
      packaging materials. The optimized MS/MS method is based on component-specific
      MRM transitions. The detection limit is component dependent and in the range of 1
      100 pg/tablet for solid dosage formulations and 0.04-4 ng/L for water based
      solutions. Deuterated tribromoanisole was used as internal standard for
      quantitation. The paper also may provide guidance for performing trace level
      method validation in the regulated Pharmaceutical Industry.

PMID- 23000181
TI  - Electrospun nanofibrous solid-phase microextraction coatings for preconcentration
      of pharmaceuticals prior to liquid chromatographic separations.
AB  - Electrospun epoxide polymer and carbon nanofiber-based SPME phases were examined
      for their application to the direct extraction of nonvolatile analytes coupled to
      liquid chromatography (LC). All of the electrospun nanofiber-coated SPME fibers
      demonstrated superior extraction efficiencies which were 2-32 times higher than a
      commercially available SPME fiber, with the electrospun coating processed at 800
      degrees C demonstrating the highest extraction efficiency. The carbonized
      electrospun nanofiber-coated SPME fibers showed no swelling when immersed in a
      variety of liquids, demonstrating the improved chemical stability these coatings
      have over traditional polymer-coated SPME fibers, which typically swell during
      direct extraction. Additionally, these robust coatings exhibit prolonged fiber
      lifetimes, withstanding up to 100 direct extractions without significant damage
      or change in nanofiber morphology. The detection limits of the method were found
      to be 2-3 orders of magnitude lower than those reported when using commercially
      available polyacrylate (PA) SPME fiber under similar conditions.

PMID- 23000182
TI  - Epithelioid hemangioma of occipital condyle and clivus: unusual location of a
      rare bony tumor with presentation in perigestational period.

PMID- 23000183
TI  - A case report of rapid spontaneous redistribution of acute supratentorial
      subdural hematoma to the entire spinal subdural space presenting as a Pourfour du
      Petit syndrome and review of the literature.
AB  - OBJECTIVE: This report illustrates the rare rapid spontaneous redistribution of
      an acute intracranial supratentorial subdural hematoma (AISSDH) to the entire
      spinal subdural space (SSS). The study is also unique in that the spinal subdural
      hematoma (SSH) manifested by the extremely rare Pourfour du Petit Syndrome (PPS).
      METHODS: A 66-year-old man sustained blunt head trauma. On admission to the
      regional hospital, he scored 6 on GCS and his pupils were of equal size reacting
      to light. Initial computed tomography (CT) scan showed a unilateral AISSDH. The
      patient was referred to our department and arrived 16 h following the accident,
      at which time a repeat CT scan revealed almost complete resolution of the AISSDH
      without clinical improvement. On the 9th postinjury day transient anisocoria and
      tachycardia without spinal symptomatology developed. Since neither neurological
      examination nor follow-up CT scans showed intracranial pathology explaining the
      anisocoria, the patient was treated further conservatively. During the next 3
      days circulatory instability developed and the patient succumbed to primary
      traumatic injury. Autopsy revealed a SSH occupying the entire SSS. CONCLUSION:
      This case calls attention to the unique combination of the displacement of an
      AISSDH to the SSS and the presentation of this clinical entity by the PPS.

PMID- 23000184
TI  - Acute cerebellar venous edema associated with unruptured cerebral arteriovenous
      malformation.

PMID- 23000185
TI  - The open abdomen: practical implications for the practicing surgeon.
AB  - The open abdomen is a necessary sequela after damage-control surgery or abdominal
      compartment syndrome. Management of the patient in the intensive care unit
      continues to evolve, with considerations of fluid resuscitation, enteral
      nutrition, and supportive care. Management of the abdominal contents incorporates
      several basic techniques and considerations: appropriate temporary covering,
      enteric injury repair in most patients, placement of an anastomosis in an area of
      the abdomen with minimal manipulation without exposure to the atmosphere,
      acquiring enteral access for initiation of enteral nutrition, and ultimate
      abdominal closure. An understanding of these complex factors is instrumental for
      the practicing surgeon.

PMID- 23000186
TI  - Acoustic Radiation Force Impulse elastography for fibrosis evaluation in patients
      with chronic hepatitis C: an international multicenter study.
AB  - AIM: The aim of this international multicenter study was to evaluate the
      reliability of Acoustic Radiation Force Impulse (ARFI) elastography for
      predicting fibrosis severity, in patients with chronic hepatitis C. PATIENTS AND
      METHODS: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5
      countries) with chronic hepatitis C. In each patient LB (evaluated according to
      the METAVIR score) and ARFI measurements were performed (median of 5-10 valid
      measurements, expressed in meters/second - m/s). In 400 from the 914 patients,
      transient elastography (TE) was also performed (median of 6-10 valid
      measurements, expressed in kiloPascals - kPa). RESULTS: Valid ARFI measurements
      were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241
      (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4
      fibrosis. A highly significant correlation (r=0.654) was found between ARFI
      measurements and fibrosis (p<0.0001). The predictive values of ARFI for various
      stages of fibrosis were: F >= 1 - cut-off>1.19 m/s (AUROC=0.779), F >= 2 - cut
      off>1.33 m/s (AUROC=0.792), F >= 3 - cut-off>1.43 m/s (AUROC=0.829), F=4 - cut
      off>1.55 m/s (AUROC=0.842). The correlation with histological fibrosis was not
      significantly different for TE in comparison with ARFI elastography: r=0.728 vs.
      0.689, p=0.28. TE was better than ARFI for predicting the presence of liver
      cirrhosis (p=0.01) and fibrosis (F >= 1, METAVIR) (p=0.01). CONCLUSION: ARFI
      elastography is a reliable method for predicting fibrosis severity in chronic
      hepatitis C patients.

PMID- 23000187
TI  - Primary adenocarcinoma of lung: a pictorial review of recent updates.
AB  - Primary adenocarcinoma of lung has replaced squamous cell carcinoma as the
      commonest histological subtype of lung cancer and the incidence of primary lung
      adenocarcinoma appears to be rising. Although the main factors behind this
      'epidemic-like' situation are largely undiscovered, filter cigarettes appear to
      significantly contribute to this shift in the histopathological spectrum. The new
      multidisciplinary classification of adenocarcinoma of lung was introduced to
      address advances in clinical, pathological, radiological and molecular sciences.
      The purpose of this essay is to discuss various classes of lung adenocarcinoma in
      the new classification with their classical imaging features on computed
      tomography and summarise the recent advances in the field of radiology and review
      radiology recommendations.

PMID- 23000188
TI  - Feasibility of ultrasound-guided high intensity focused ultrasound ablating
      uterine fibroids with hyperintense on T2-weighted MR imaging.
AB  - PURPOSE: To retrospectively investigate whether uterine fibroids with
      hyperintense on pretreatment T2-weighted magnetic resonance imaging (MRI) could
      be treated with ultrasound-guided high intensity focused ultrasound (USgHIFU).
      MATERIALS AND METHODS: 282 patients with 282 symptomatic uterine fibroids who
      underwent USgHIFU treatment were retrospectively analyzed. Based on the signal
      intensity of T2-weighted MRI, uterine fibroids were classified as hypointense,
      isointense and hyperintense. Hyperintense fibroids were subjectively further
      subdivided into heterogeneous hyperintense, slightly homogeneous hyperintense and
      markedly homogeneous hyperintense based on the signal intensity of fibroid
      relative to myometrium and endometrium on T2-weighted MRI. Enhanced MRI was
      performed within one month after HIFU treatment. Non-perfused volume (NPV,
      indicative of successful ablation) ratio, treatment time, treatment efficiency,
      energy effect ratio and adverse events were recorded. RESULTS: The median volume
      of uterine fibroids was 70.3 cm(3) (interquartile range, 41.1-132.5 cm(3)). The
      average NPV ratio, defined as non-perfused volume divided by the fibroid volume
      after HIFU treatment, was 76.8 +/- 19.0% (range, 0-100%) in the 282 patients. It
      was 86.3 +/- 11.9% (range, 40.9-100.0%) in the group with hypointense fibroids,
      77.1 +/- 16.5% (range, 32.2-100.0%) in isointense fibroids, and 67.6 +/- 23.9%
      (range, 0-100.0%) in hyperintense fibroids. The lowest NPV ratio, lowest
      treatment efficiency, more treatment time, more sonication energy and pain scores
      were observed in the slightly homogeneous hyperintense fibroids, and the NPV
      ratio was 55.8 +/- 26.7% (range, 0-83.9%) in this subgroup. CONCLUSION: Based on
      our results, the heterogeneous and markedly homogeneous hyperintense fibroids
      were suitable for USgHIFU, and only the slightly homogeneous hyperintense
      fibroids should be excluded.

PMID- 23000189
TI  - Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes
      with trastuzumab in a breast cancer brain metastasis model.
AB  - Trastuzumab has shown positive results in many patients with metastatic HER2
      positive breast cancer, but it is less effective for controlling metastases in
      the CNS, which remains a site of relapse. The poor prognosis for patients with
      brain metastases is thought to be largely due to the presence of the blood-brain
      barrier (BBB) that prevents delivery of most drugs to the CNS and to the
      heterogeneous and limited permeability of the blood-tumor barrier (BTB). Focused
      ultrasound (FUS) bursts combined with circulating microbubbles can temporarily
      permeabilize both the BBB and the BTB. This technique has been investigated as a
      potential noninvasive method for targeted drug delivery in the brain. Here, we
      investigated whether BBB/BTB permeabilization in the tumor and surrounding brain
      tissue induced by FUS and microbubbles can slow tumor growth and improve survival
      in a breast cancer brain metastases model. HER2/neu-positive human breast cancer
      cells (BT474) were inoculated in the brains of 41 nude (nu/nu) rats. Animals in
      the treatment group received six weekly treatments of BTB/BBB permeabilization
      under MRI guidance combined with IV administration of trastuzumab (2 mg/kg).
      Tumor growth and survival rates were monitored via MRI for seven weeks after
      sonication. Starting at week seven and continuing through the end of the study,
      the mean tumor volume of the FUS+trastuzumab group was significantly (P<0.05)
      less than those of the three control groups (no treatment, FUS alone, trastuzumab
      alone). Furthermore, in four out of 10 rats treated with FUS+trastuzumab, the
      tumor appeared to be completely resolved in MRI, an outcome which was not
      observed in any of the 31 rats in three control groups. Trastuzumab improved
      median survival by 13% compared to the no treatment group, a difference which was
      significant (P=0.044). Treatment with FUS+trastuzumab produced the most
      significant benefit compared to the no-treatment controls (P=0.0084). More than
      half (6/10) animals survived at the study endpoint, leading to a median survival
      time greater than 83 days (at least 32% longer than the untreated control group).
      Overall, this work suggests that BBB/BTB permeabilization induced by FUS and
      microbubbles can improve outcomes in breast cancer brain metastases.

PMID- 23000190
TI  - The vitamin D analog TX527 ameliorates disease symptoms in a chemically induced
      model of inflammatory bowel disease.
AB  - The vitamin D system plays a critical role in inflammatory bowel disease as
      evidenced by the finding that both vitamin D deficient mice and vitamin D
      receptor knockout mice are extremely sensitive to dextran sodium sulfate (DSS)
      induced colitis. Moreover, the active form of vitamin D, 1alpha,25
      dihydroxyvitamin D3 [1,25(OH)2D3] is an important immunomodulator that
      ameliorates the pathogenesis of inflammatory bowel disease. However, therapeutic
      application of 1,25(OH)2D3 is hampered by its calcemic activity. Previous work
      illustrated that the analog 1alpha,25(OH)2-19-nor-14,20-bisepi-23-yne-vitamin D3
      (TX527) has potent antiproliferative effects with limited calcemic activity. In
      the present study we demonstrated that TX527 ameliorated disease symptoms in a
      DSS-induced model of inflammatory bowel disease. TX527 significantly attenuated
      disease scores, by suppressing bleeding and diarrhea. Colon length was
      significantly elevated at the end of the experiment. Histological examination
      indicated that TX527 diminished mucosal damage and crypt loss and suppressed the
      infiltration of immune cells in DSS-induced colitis mice. Furthermore, transcript
      levels of inflammatory cytokines such as IL-1, IL-6, IFN-gamma and TNF-alpha were
      significantly down-regulated in colonic mucosa of mice with colitis. Moreover,
      transcript levels of the gastrointestinal glutathione peroxidase 2, which acts as
      a radical scavenger, were significantly down-regulated after TX527 treatment in
      DSS-colitis mice. These results indicate that TX527 may have a therapeutic value
      in the setting of inflammatory bowel disease. This article is part of a Special
      Issue entitled 'Vitamin D Workshop'.

PMID- 23000191
TI  - Effects of nuclear receptor transactivation on steroid hormone synthesis and gene
      expression in porcine Leydig cells.
AB  - Male pigs are routinely castrated at a young age to prevent the formation of
      androstenone, a 16-androstene testicular steroid that is a major component of
      boar taint. The practice of castration has been increasingly viewed as
      unfavorable, due to both economic considerations and animal welfare concerns.
      Other means of controlling boar taint, including reducing the synthesis of
      androstenone in the testes, would eliminate the need for castration. In this
      study, we determined the effects of transactivation of three nuclear receptors,
      the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and
      farnesoid X receptor (FXR), on gene expression and steroid hormone metabolism in
      primary porcine Leydig cells. Primary cells were isolated from mature boars, and
      transcript expression levels were assayed using real-time PCR. The transcripts of
      interest included porcine orthologs of common phase I and phase II metabolic
      enzymes, enzymes involved in steroidogenesis, and transcripts previously shown to
      be differentially expressed in boars with high androstenone and boar taint
      levels. Transactivation of CAR, PXR, or FXR increased the expression of several
      genes involved in steroidogenesis, including cytochrome B5A (CYB5A) and
      cytochrome B5 reductase 1 (CYB5R1), as well as hydroxysteroid (17-beta)
      dehydrogenase 4 (HSD17B4) and retinol dehydrogenase 12 (RDH12). Treatment with (6
      (4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4
      dichlorobenzyl)oxime (CITCO), a CAR agonist, or rifampicin (RIF), a PXR agonist,
      resulted in significantly (p<0.05) decreased sex steroid production and
      significantly (p<0.05) increased production of 16-androstene steroids. Treatment
      with the FXR agonist chenodeoxycholic acid (CDCA) resulted in significantly
      (p<0.05) decreased sex steroid production. These results indicate that
      transactivation of these nuclear receptors may lead to increased levels of 16
      androstene steroids, likely by altering the activity of CYP17A1 through CYB5A and
      CYB5R1 to the andien-beta synthase reaction and away from the 17alpha-hydroxylase
      and C17, 20 lyase reactions.

PMID- 23000192
TI  - Interval-valued analysis for discriminative gene selection and tissue sample
      classification using microarray data.
AB  - An important application of gene expression data is to classify samples in a
      variety of diagnostic fields. However, high dimensionality and a small number of
      noisy samples pose significant challenges to existing classification methods.
      Focused on the problems of overfitting and sensitivity to noise of the dataset in
      the classification of microarray data, we propose an interval-valued analysis
      method based on a rough set technique to select discriminative genes and to use
      these genes to classify tissue samples of microarray data. We first select a
      small subset of genes based on interval-valued rough set by considering the
      preference-ordered domains of the gene expression data, and then classify test
      samples into certain classes with a term of similar degree. Experiments show that
      the proposed method is able to reach high prediction accuracies with a small
      number of selected genes and its performance is robust to noise.

PMID- 23000193
TI  - Evaluating coverage of exons by HapMap SNPs.
AB  - Genome-wide association (GWA) studies are currently one of the most powerful
      tools in identifying disease-associated genes or variants. In typical GWA
      studies, single-nucleotide polymorphisms (SNPs) are often used as genetic makers.
      Therefore, it is critical to estimate the percentage of genetic variations which
      can be covered by SNPs through linkage disequilibrium (LD). In this study, we use
      the concept of haplotype blocks to evaluate the coverage of five SNP sets
      including the HapMap and four commercial arrays, for every exon in the human
      genome. We show that although some Chips can reach similar coverage as the
      HapMap, only about 50% of exons are completely covered by haplotype blocks of
      HapMap SNPs. We suggest further high-resolution genotyping methods are required,
      to provide adequate genome-wide power for identifying variants.

PMID- 23000195
TI  - Resveratrol upregulated heat shock proteins and extended the survival of G93A
      SOD1 mice.
AB  - In the present study, we investigated whether resveratrol, a SIRT1 activator, can
      suppress the motor neuron degeneration in a transgenic mouse model of amyotrophic
      lateral sclerosis. Chronic intraperitoneal injection of resveratrol delayed the
      disease onset and extended survival of the transgenic mice overexpressing G93A
      SOD1. The number of surviving motor neurons increased in the resveratrol-injected
      G93A mice. Importantly, the levels of Hsp25 and Hsp70 were elevated while the
      level of heat shock factor 1 (HSF1) acetylation decreased in the spinal cords of
      the resveratrol-injected G93A mice. Our data suggest that resveratrol may protect
      motor neurons from the mutant SOD1-induced neurotoxicity by promoting SIRT1
      mediated deacetylation of HSF1 and subsequent upregulation of Hsps.

PMID- 23000194
TI  - Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to
      transformed human lung cells in vitro.
AB  - Environmental exposure to cadmium is known to cause damage to alveolar epithelial
      cells of the lung, impair their capacity to repair, and result in permanent
      structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can
      modulate cell responses to injury through their interactions with soluble
      effector molecules. These interactions are often sulfate specific, and the
      removal of sulfate groups from HS side chains could be expected to influence
      cellular injury, such as that caused by exposure to cadmium. The goal of this
      study was to define the role 6-O-sulfate plays in cellular responses to cadmium
      exposure in two pulmonary epithelial cancer cell lines (H292 and A549) and in
      normal human primary alveolar type II (hAT2) cells. Sulfate levels were modified
      by transduced transient over-expression of 6-O-endosulfatase (HSulf-1), a
      membrane-bound enzyme which specifically removes 6-O-sulfate groups from HSPG
      side chains. Results showed that cadmium decreased cell viability and activated
      apoptosis pathways at low concentrations in hAT2 cells but not in the cancer
      cells. HSulf-1 over-expression, on the contrary, decreased cell viability and
      activated apoptosis pathways in H292 and A549 cells but not in hAT2 cells. When
      combined with cadmium, HSulf-1 over-expression further decreased cell viability
      and exacerbated the activation of apoptosis pathways in the transformed cells but
      did not add to the toxicity in hAT2 cells. The finding that HSulf-1 sensitizes
      these cancer cells and intensifies the injury induced by cadmium suggests that 6
      O-sulfate groups on HSPGs may play important roles in protection against certain
      environmental toxicants, such as heavy metals.

PMID- 23000196
TI  - Intracerebroventricular injection of HAMI 3379, a selective cysteinyl leukotriene
      receptor 2 antagonist, protects against acute brain injury after focal cerebral
      ischemia in rats.
AB  - Cysteinyl leukotrienes (CysLTs) induce inflammatory responses by activating their
      receptors, CysLT(1)R and CysLT(2)R. We recently reported that CysLT(2)R is
      involved in neuronal injury, astrocytosis and microgliosis after focal cerebral
      ischemia in rats. Here, we determined whether HAMI 3379, a selective CysLT(2)R
      antagonist, protects against acute brain injury after focal cerebral ischemia in
      rats. We induced transient focal cerebral ischemia by 30 min of middle cerebral
      artery occlusion (MCAO), followed by 24h of reperfusion. HAMI 3379 (1, 10 or 100
      ng) was injected intracerebroventricularly (i.c.v.) 30 min before MCAO, and the
      CysLT(1)R antagonist pranlukast (0.1mg/kg, i.p.) was used as a positive control.
      HAMI 3379 at 10 and 100 ng (but not at 1 ng) attenuated the neurological
      deficits, and reduced infarct volume, brain edema, IgG exudation, neuronal
      degeneration and neuronal loss. This protective effect was similar to that of
      pranlukast. Thus, HAMI 3339 at 10-100 ng i.c.v. is neuroprotective against acute
      brain injury after focal cerebral ischemia in rats. These findings suggest
      therapeutic potential for CysLT(2)R antagonists in the treatment of ischemic
      stroke.

PMID- 23000197
TI  - Cisplatin induces changes in the matrix metalloproteinases and their inhibitors
      in the developing rat cerebellum.
AB  - The role of matrix metalloproteinases (MMP-3 and MMP-9), tissue inhibitor of MMP
      (TIMP-2), and GAP-43 (growth-associated-protein) in neocerebellar vermis lobules
      during postnatal histogenesis was studied after challenge with cisplatin (cisPt).
      CisPt is one of the most effective and widely used cytotoxic agents in the
      treatment of a variety of malignancies, in both children and adult patients. A
      single injection of cisPt to 10-day-old rats altered the spatiotemporal MMP/TIMP
      expression balance and provoked a decrease in GAP43 immunoreactivity. The
      imbalance appeared one day (PD11) after cisPt injection, producing disorder of
      cerebellum histogenesis processes in which MMPs might be involved, i.e. genesis
      of granule cells, Purkinje cell differentiation and synaptogenesis. Following the
      early injury, a simultaneous increase in MMP and TIMP expression in the ML was
      noticed at PD17, likely initiating recovery of Purkinje cell dendrite growth and
      remodelling processes. However, disturbances at the beginning of recovery phase
      had emerged, probably due to the down-regulation of GAP-43 after cisPt treatment.
      The data provide further support for the usefulness of cisPt as a tool for the
      study of morphological and functional changes in the CNS during postnatal
      development.

PMID- 23000198
TI  - Brain infarct volume after permanent focal ischemia is not dependent on Nox2
      expression.
AB  - Reactive oxygen species (ROS) generated by Nox2 oxidase are reported to
      contribute to infarct damage following cerebral ischemia-reperfusion. Here we
      have examined for the first time the role of Nox2 expression in outcomes
      following permanent focal cerebral ischemia. Ischemia was induced by middle
      cerebral artery filament occlusion (MCAO) for 24h in wild-type (WT) and Nox2(-/y)
      mice. Neurological deficit and the hanging wire test were assessed, and infarct
      and edema volumes were estimated using thionin-stained brain sections. Genetic
      deletion of Nox2 had no effect on any outcome measures at 24h after permanent
      MCAO. Our data therefore suggest that ROS production by Nox2 oxidase activity
      plays no significant role in the pathophysiology of cerebral ischemia in the
      absence of reperfusion.

PMID- 23000199
TI  - Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins.
AB  - The mechanism by which myristoylated proteins are targeted to specific
      subcellular membrane compartments is poorly understood. Two novel acyl-binding
      proteins, UNC119A and UNC119B, have been shown recently to function as
      chaperones/co-factors in the transport of myristoylated G protein alpha-subunits
      and src-type tyrosine kinases. UNC119 polypeptides feature an immunoglobulin-like
      beta-sandwich fold that forms a hydrophobic pocket capable of binding lauroyl
      (C12) and myristoyl (C14) side chains. UNC119A in rod photoreceptors facilitates
      the transfer of transducin alpha subunits (Talpha) from inner segment to outer
      segment membranes by forming an intermediate diffusible UNC119-Talpha complex.
      Similar complexes are formed in other sensory neurons, as the G proteins ODR-3
      and GPA-13 in Caenorhabditis elegans unc-119 mutants traffic inappropriately.
      UNC119B knockdown in IMCD3 cells prevents trafficking ofmyristoylated
      nephrocystin-3 (NPHP3), a protein associated with nephronophthisis, to cilia.
      Further, UNC119A was shown to transport myristoylated src-type tyrosine kinases
      to cell membranes and to affect T-cell receptor (TCR) and interleukin-5 receptor
      (IL-5R) activities. These interactions establish UNC119 polypeptides as novel
      lipid-binding chaperones with specificity for a diverse subset of myristoylated
      proteins.

PMID- 23000200
TI  - TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to
      endometriosis-related infertility.
AB  - INTRODUCTION: Tyrosine kinase 2 gene (TYK2) is part of the janus kinase (JAK)
      that binds to the type I interferon-alpha receptor (IFNAR) on the cell surface of
      IFN-producing cells, and have crucial importance in the etiology of autoimmune
      and inflammatory diseases. Many polymorphisms of the TYK2 gene have been
      identified, and recently, a number of case-control studies were conducted to
      investigate the association of these polymorphisms with autoimmune and
      inflammatory diseases, with conflicting results. Based on these observations, we
      hypothesized that the TYK2 polymorphisms (rs34536443, rs2304256, rs280523,
      rs12720270 and rs12720356) might be involved in the pathogenesis of endometriosis
      and/or infertility. METHODS: Genetic association study comprising 275 infertile
      women with endometriosis, 92 women with idiopathic infertility and 307 fertile
      women as controls. TYK2 polymorphisms were identified by TaqMan PCR. Genotype
      distribution, allele frequency and haplotype analysis of the TYK2 polymorphisms
      were performed. A p-value <0.05 was considered significant. RESULTS: Single
      marker analysis revealed that TYK2 rs34536443 was significantly associated with
      protection against endometriosis-related infertility, especially in
      moderate/severe disease (p = 0.002; OR = 0.24, 95% IC = 0.09-0.62). No difference
      was found considering the infertile group without endometriosis. No associations
      were found considering rs2304256, rs280523, rs12720270 and rs12720356 either for
      endometriosis-related infertility group or idiopathic infertility group.
      Haplotype analysis of five TYK2 polymorphisms identified a haplotype "CTATG"
      associated with protection against endometriosis-related infertility, especially
      in moderate/severe disease (p = 0.027). CONCLUSION: This is the first study to
      report an association between TYK2 polymorphisms and endometriosis and/or
      infertility. These findings require replication in other populations but suggest
      the TYK2 rs34536443 polymorphisms and "CTATG" haplotype can be associated with a
      decreased susceptibility to endometriosis-related infertility in Brazilian women.

PMID- 23000202
TI  - Neutropenia as a potential pharmacodynamic marker for docetaxel-based
      chemotherapy in men with metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: Docetaxel clearance appears increased in men who are castrated.
      Neutropenia in cycle 1 may be a pharmacodynamic marker for docetaxel, which may
      enable tailored dosing in metastatic castration-resistant prostate cancer
      (mCRPC). PATIENTS AND METHODS: The association of cycle 1 neutropenia with
      overall survival (OS) was examined post hoc in a randomized phase II trial of 221
      men with mCRPC who received docetaxel-prednisone combined with placebo or AT-101
      (bcl-2 inhibitor); weekly blood cell counts were performed during the first
      cycle. Patients from both arms were combined because no outcome and toxicity
      differences were observed. OS was calculated from randomization by the Kaplan
      Meier method, and Cox proportional hazards regression models were used to
      estimate the association with OS. RESULTS: The difference in OS between men with
      day 8 >=grade 3 neutropenia and those with <=grade 2 neutropenia was significant
      after adjusting for trial stratification factors, pain, and performance status
      (hazard ratio [HR] 0.64; 2P = .048). Results were similar for logarithmic
      neutrophil counts adjusted for the risk group based on anemia, visceral
      metastasis, progression by bone scan and pain (HR 1.18; 2P = .07) for
      stratification factors (HR 1.20; 2P = .052) or both (HR, 1.20; 2P = .046). Men
      with >=grade 3 neutropenia and >=30% prostate-specific antigen level decline by
      day 90 had improved OS compared with men exhibiting neither (HR 0.51; 2P = .014).
      CONCLUSIONS: For patients with mCRPC who received docetaxel, >=grade 3
      neutropenia on day 8 was prognostic for improved OS, which suggests its utility
      as a pharmacodynamic marker, in this hypothesis-generating analysis. Exploration
      of dose escalation of docetaxel to attain >=grade 3 neutropenia on day 8 may be
      warranted.

PMID- 23000201
TI  - Association between interleukin-8 gene -251 T/A polymorphism and the risk of
      peptic ulcer disease: a meta-analysis.
AB  - It remains controversial regarding the association between interleukin-8 (IL-8)
      gene -251 T/A polymorphism and peptic ulcer disease (PUD) risk. Thus, a large
      scale meta-analysis evaluating the precise association between this gene variant
      and PUD risk is required. We searched the PubMed, Embase, Web of Science, and
      Google Scholar until April 25, 2012. Additionally, hand searching of the
      references of identified articles were performed. All the statistical tests were
      performed using Stata 11.0. A total of eight studies (3105 subjects) were
      included in this meta-analysis. Overall, no significant association was found
      between IL-8 gene -251 T/A polymorphism and PUD risk (for A allele vs. T allele:
      OR = 1.17, 95% CI = 0.97-1.41, p = 0.094; for A/A vs. T/T: OR = 1.33, 95% CI =
      0.94-1.90, p = 0.108; for A/A vs. A/T+T/T: OR = 1.22, 95% CI =0.97-1.52, p =
      0.083; for A/A+A/T vs. T/T: OR = 1.26, 95% CI = 0.95-1.67, p = 0.113). However,
      in the subgroup analyses by ethnicity, H. pylori infection and the subtype of
      PUD, significant associations were found between IL-8 gene -251 T/A polymorphism
      and PUD risk in Asians, H. pylori+, duodenal ulcer disease (DUD) and gastric
      ulcer disease (GUD), respectively. In summary, the present meta-analysis suggests
      that IL-8 gene -251 T/A polymorphism is associated with increased PUD risk among
      Asians, and especially for the subgroups of H. pylori+, DUD and GUD.

PMID- 23000203
TI  - Complex metabolic and skeletal changes in men taking long-term androgen
      deprivation therapy.
AB  - BACKGROUND: The objective of this study was to assess complex skeletal and
      metabolic changes in a single cohort of PCa patients taking long-term ADT.
      PATIENTS AND METHODS: Ninety-five patients with locally advanced PCa (mean age
      73.3 +/- 6.2 years) were treated with ADT for 24 months. Body mass index (BMI),
      waist-to-hip ratio (WHR), lipid profile, serum fasting glucose (SFG), and bone
      mineral density (BMD) of lumbar spine (L1-L4), femoral neck, and total hip BMD
      were examined at the baseline, and then every 12 months. These measurements were
      also made to the control group of 88 patients (mean age, 71.9 +/- 6.7 years).
      RESULTS: After 12 months of ADT, BMI, WHR, low-density lipoprotein, overall
      cholesterol, and SFG increased significantly; and total hip BMD and BMD L1-L4
      decreased significantly in the study group. After 24 months of ADT, BMI, WHR, and
      SFG increased significantly. BMD was significantly lower in L1-L4, femoral neck,
      and total hip. Four patients (4.2%) were diagnosed with new onset diabetes.
      Overall, the incidence of fractures after 24 months of ADT was 7-fold higher in
      the study group. CONCLUSION: ADT leads into unfavorable changes in body
      composition, unfavorable lipoprotein profile, increase in SFG level and decrease
      in BMD. The incidence of fractures was 7-fold higher in the study group.

PMID- 23000207
TI  - Emerging and critical issues in the pathogenesis of lupus.
AB  - Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease,
      encompassing either mild or severe manifestations. SLE was originally labeled as
      being an immune complex-mediated disease, but further knowledge suggested its
      pathogenesis is motlier than that, involving complex interactions between
      predisposed individuals and their environment. People affected with SLE have
      their immune system skewed toward aberrant self-recognition usually after
      encountering a triggering agent. Defeats in early and late immune checkpoints
      contribute to tolerance breakdown and further generation and expansion of
      autoreactive cell-clones. B and T cells play a master role in SLE, however clues
      are emerging about other cell types and new light is being shed on SLE
      autoantibodies, since some of them display really harmful potential (pathogenic
      antibodies), while others are just connected with disease development
      (pathological antibodies) and may even be protective. Autoantibody generation is
      elicited by abnormal apoptosis and inefficient clearance of cellular debris
      causing intracellular autoantigens (e.g. nucleosomes) to persist in the
      extracellular environment, being further recognized by autoreactive cells. Here
      we explore the complexity of SLE pathogenesis through five core issues, i.e.
      genetic predisposition, B and T cell abnormalities, abnormal autoantigen
      availability, autoantibody generation and organ damage, relying on current
      knowledge and recent insights into SLE development.

PMID- 23000208
TI  - A new sensitive organic/inorganic hybrid material based on titanium oxide for the
      potentiometric detection of iron(III).
AB  - The formation of a new hybrid material based on titanium dioxide as inorganic
      support and containing an iron organochelator (ICL670) is described. An
      organophosphorous coupling agent was used to graft the organic molecule on the
      oxide surface. The attachment of the organic substrate was well-confirmed by FTIR
      (DRIFT), solid-state (31)P and (13)C CPMAS NMR, thermal analysis and the
      integrity of the structural and morphological parameters were verified using XRD
      and TEM analyses. The interaction between the material and dissolved iron(III)
      was also investigated through potentiometric measurements and demonstrated the
      interest of this new non-siliceous based hybrid material. The obtained linear
      evolution of the open circuit potential from 10(-2) to 10(-6) mol L(-1) can be
      used for the analytical detection of iron(III).

PMID- 23000205
TI  - Gene network analysis of small molecules with autoimmune disease associated genes
      predicts a novel strategy for drug efficacy.
AB  - Numerous genes/SNPs in autoimmune diseases (ADs) are identified through genome
      wide association studies (GWAS) and likely to contribute in developing autoimmune
      phenotypes. Constructions of biologically meaningful pathways are necessary to
      determine how these genes interact with each other and with other small molecules
      to develop various complex AD phenotypes prior to beginning time-consuming
      rigorous experimentation. We have constructed biological pathways with
      genetically identified genes leading to shared AD phenotypes. Various
      environmental and endogenous factors interact with these AD associated genes
      suggesting their critical role in developing diseases and further association
      studies could be designed for assessing the role of these factors with risk
      allele in a specific gene. Additionally, existing drugs that have been used long
      before the identification of these genetically associated genes also interact
      with these newly associated genes. Thus advanced therapeutic strategies could be
      designed by grouping patients with risk allele(s) in particular genes that
      directly or closely interact with the specified drugs. This drug-susceptible gene
      network will not only increase our understanding about the additional molecular
      basis for effectiveness against these diseases but also indicate which drug could
      be more effective for those patients carrying risk allele(s) in that gene.
      Additionally, we have also identified several interlinking genes in the pathways
      that could be used for designing future association studies.

PMID- 23000209
TI  - Fine encapsulation of dual-particle electronic ink by incorporating block
      copolymer for electrophoretic display application.
AB  - The design of the oppositely charged ink particles based on titanium dioxide and
      carbon black for the monochrome electrophoretic display (EPD) was reported. The
      white ink particles with acidic surface and black ink particles with basic
      surface were synthesized and sterically stabilized by long alkyl chains, which
      were charged oppositely by mixing with basic surfactant (OLOA 1200) and acidic
      surfactant (Span 80), respectively. The electrophoretic mobility and the Zeta
      potential were -3.87*10(-10)m(2)V(-1)s(-1) and -25.1 mV for the white ink
      particles, 3.79*10(-10)m(2)V(-1)s(-1) and 24.6 mV for the black ink particles. In
      addition, the block copolymer, poly(lauryl methacrylate)-b-poly(2
      (dimethylamino)ethyl methacrylate) (PLMA-b-PDMAEMA) synthesized by atom transfer
      radical polymerization (ATRP), was first incorporated in the modification of the
      pigments for the fine encapsulation. Then, a stable dual-particle electronic ink
      with contrast ratio of 120:1 was prepared and encapsulated with the gelatin
      (GE)/sodium carboxymethylcellulose (NaCMC)/sodium dodecyl sulfate (SDS)
      microcapsules by complex coacervation method. Finally, the matrix character
      display prototype driven at a low voltage exhibited excellent performance, the
      contrast ratio of which was 8:1 at 9 V DC.

PMID- 23000206
TI  - Cutaneous lupus erythematosus: first multicenter database analysis of 1002
      patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE).
AB  - In this prospective, cross-sectional, multicenter study, we assessed clinical and
      laboratory characteristics from patients with cutaneous lupus erythematosus (CLE)
      using the Core Set Questionnaire of the European Society of Cutaneous Lupus
      Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different
      subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236
      patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65
      patients), from 13 European countries were collected and statistically analyzed
      by an SPSS database. The main outcome measures included gender, age at onset of
      disease, LE-specific and LE-nonspecific skin lesions, photosensitivity,
      laboratory features, and the criteria of the American College of Rheumatology
      (ACR) for the classification of systemic lupus erythematosus. The mean age at
      onset of disease was 43.0+/-15.7 years and differed significantly between the CLE
      subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were
      diagnosed during the course of the disease and 453 (45.2%) presented with LE
      nonspecific manifestations. Drug-induced CLE and Sjogren's Syndrome had the
      highest prevalence in SCLE patients (13.1% and 14.0%, respectively).
      Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and
      ICLE compared with those with CCLE. The detection of antinuclear antibodies such
      as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant
      differences between the CLE subtypes. In summary, the EUSCLE Core Set
      Questionnaire and its database facilitate the analysis of clinical and laboratory
      features in a high number of patients with CLE and will contribute to
      standardized assessment and monitoring of the disease in Europe.

PMID- 23000210
TI  - Synthesis and characterization of magnetic hexacyanoferrate (II) polymeric
      nanocomposite for separation of cesium from radioactive waste solutions.
AB  - Nanocrystalline potassium zinc hexacyanoferrate loaded on nanoscale magnetite
      substrate was successfully synthesized for significantly enhanced removal of
      cesium from low-level radioactive wastes. A description was given for preparation
      and properties of these precursors. The physicochemical properties of these
      nanocomposites were determined using different techniques including Fourier
      transform infrared spectroscopy (FTIR), X-ray diffraction (XRD),
      thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and energy
      dispersive spectroscopy (EDS). Data clarified that supporting potassium zinc
      hexacyanoferrates on iron ferrite nanoparticles increased their thermal
      stability. Further, Fourier transform infrared spectra confirmed that the
      nanocomposites were well coordinated and incorporated in the polymer matrix. The
      average particle sizes, of these nanoparticles, determined by SEM had a good
      agreement with XRD results. Based on characterization data, the prepared zinc
      hexacyanoferrates were proposed to have a zeolitic rhombohedral structure with
      cavities can host alkali metal ions and water molecules. The magnetic analysis
      showed a super-paramagnetic behavior. Batch technique was applied to evaluate the
      influences of initial pH value, contact time, and competing cations on the
      efficiency of cesium removal. The sorption process was fast initially, and
      maximum separation was attained within 2h of contact. Cesium exchange was
      independent from pH value and deviate from ideal exchange phenomena. In neutral
      solutions, Cs(+) was retained through exchange with K(+); however, in acidic
      solution, phase transformation was proposed. Sorption capacity of these materials
      attained values amounted 1965 mg g(-1). The synthesized nanocomposites exhibited
      different affinities toward Cs(I), Co(II), and Eu(III) elements and showed a good
      ability to separate them from each other.

PMID- 23000211
TI  - As(V) and As(III) reactions on pristine pyrite and on surface-oxidized pyrite.
AB  - Reactions of As(III) and As(V) with pyrite were investigated using pristine
      pyrite (produced and reacted in a rigorously anoxic environment with P(O2)<10(
      8)atm) and using surface-oxidized pyrite (produced under anoxic conditions,
      exposed to air, then stored and reacted under rigorously anoxic conditions).
      Results with surface-oxidized pyrite were similar to previously reported arsenic
      pyrite results. However As(III) adsorbed over a broader pH range on pristine
      pyrite than on surface-oxidized pyrite, As(V) adsorbed over a narrower pH range
      on pristine pyrite than on surface-oxidized pyrite, and adsorbed As(V) on
      pristine pyrite was reduced to As(III) but adsorbed As(V) was not reduced with
      surface-oxidized pyrite. Reduction of As(V) with pristine pyrite was first-order
      in total As(V), Fe(II) was released, and sulfur was oxidized. The proposed
      mechanism for pyrite oxidation by As(V) was similar to the published mechanism
      for oxidation by O(2) and rates were compared. The results can be used to predict
      the removals of As(V) and As(III) on pyrite in continuously anoxic environments
      or on pyrite in intermittently oxic/anoxic environments. Rigorous cleanup and
      continuous maintenance of strictly anoxic conditions are required if commercial
      or produced pyrites are to be used as surrogates for pristine pyrite.

PMID- 23000204
TI  - Cytokine effects on the basal ganglia and dopamine function: the subcortical
      source of inflammatory malaise.
AB  - Data suggest that cytokines released during the inflammatory response target
      subcortical structures including the basal ganglia as well as dopamine function
      to acutely induce behavioral changes that support fighting infection and wound
      healing. However, chronic inflammation and exposure to inflammatory cytokines
      appears to lead to persisting alterations in the basal ganglia and dopamine
      function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover,
      reduced neural responses to hedonic reward, decreased dopamine metabolites in the
      cerebrospinal fluid and increased presynaptic dopamine uptake and decreased
      turnover have been described. This multiplicity of changes in the basal ganglia
      and dopamine function suggest fundamental effects of inflammatory cytokines on
      dopamine synthesis, packaging, release and/or reuptake, which may sabotage and
      circumvent the efficacy of current treatment approaches. Thus, examination of the
      mechanisms by which cytokines alter the basal ganglia and dopamine function will
      yield novel insights into the treatment of cytokine-induced behavioral changes
      and inflammatory malaise.

PMID- 23000212
TI  - Solid-state electron transport in Mn-, Co-, holo-, and Cu-ferritins: force
      induced modulation is inversely linked to the protein conductivity.
AB  - In this work, solid-state electron transport through the three metal core
      reconstituted ferritins, namely, Mn(III)-ferritin, Co(III)-ferritin, and Cu(II)
      ferritin, has been probed and compared to the electron transport via the
      naturally-occurring iron-containing holoferritin and the metal-free apoferritin
      using current sensing atomic force spectroscopy (CSAFS), which allows direct
      contact to be established with the protein molecules. The CSAFS results reveal
      that by applying compressional force, in varying degrees (17-66 nN) and for
      varying durations (1 min, 2 min, and 3 min), the electronic conductivity of these
      proteins can be increased (for greater amount of force applied or for prolonged
      application of force) or decreased (for lesser amount of force applied or for
      shorter application time). The compressional modulation of the electronic
      conductivities appears to be due to compression of the protein part. The
      observation of the order of electronic conductivities of Mn-, holo-, Co-, and Cu
      ferritins at almost any specific force value being similar to that of the free
      metal conductivities indicates that the absolute conductivity values are directly
      influenced by the metal core. Importantly, we found that more conductive the
      protein is, less modulated it can be. These findings could be highly relevant in
      realizing metalloprotein-based bioelectronic devices, especially where the
      electrode-protein-electrode sandwich configurations are employed.

PMID- 23000213
TI  - [Ratification of UE 4.4 S4 "simulated blood transfusion": inquiry and answers].
AB  - The new training reference guide related to state registered degree has been
      applied since 31 July 2009. Training and valuation projects developed by nurse
      training institutes have been amended to comply with learning concept:
      understanding-action-transfer. Validation of grade 4.4 S4 is part of competence 4
      validation "implementation of actions related to diagnostic and therapy". The
      requirement for all students to ratify simulated transfusion lead teachers to
      update their knowledge and to be more committed to knowledge acquisition. To
      complete its work, the research and quality control department of the French
      Transfusion Company regarding the result of the national 2011 inquiry, proposes
      in relation with the National Transfusion Institute to provide the professional
      network with tools and supports making knowledge exchanges and experience sharing
      easier. The reference transfusional teaching guide updating intended to training
      institutes is being carried out and considered as a priority.

PMID- 23000214
TI  - [Interest of transfusion safety e-learning for nurses: assessment after two
      years].
AB  - In front of increasing organizational difficulties, health institutions opted for
      a transfusion safety e-learning training. Hindsight of two years, an initial
      assessment highlights success factors and desirable improvements.

PMID- 23000215
TI  - Synthesis of alpha-galactosyl epitopes by metabolically engineered Escherichia
      coli.
AB  - The alpha-Gal epitope is a carbohydrate structure, Galalpha-3Galbeta-4GlcNAc-R,
      expressed on glycoconjuguates in many mammals, but not in humans. Species that do
      not express this epitope have present in their serum large amounts of natural
      anti-Gal antibodies, which contribute to organ hyperacute rejection during
      xenotransplantation. We first describe the efficient conversion of lactose into
      isoglobotriaose (Galalpha-3Galbeta-4Glc) using high cell density cultures of a
      genetically engineered Escherichia coli strain expressing the bovine gene for
      alpha-1,3-galactosyltransferase. Attempts to produce the Galili pentasaccharide
      (Galalpha-3Galbeta-4GlcNAcbeta-3Galbeta-4Glc) by additionally expressing the
      Neisseria meningitis lgtA gene for beta-1,3-N-acetylglucosaminyltransferase and
      the Helicobacter pylori gene for beta-1,4-galactosyltransferase were unsuccessful
      and led to the formation of a series of long chain oligosaccharides formed by the
      repeated addition of the trisaccharide motif [Galbeta-4GlcNAcbeta-3Galalpha-3]
      onto a lacto-N-neotetraose primer. The replacement of LgtA by a more specific
      beta-1,3-N-acetylglucosaminyltransferase from H. pylori, which was unable to
      glycosylate alpha-galactosides, prevented the formation of these unwanted
      compounds and allowed the successful formation of the Galili pentasaccharide and
      longer alpha-Gal epitopes.

PMID- 23000216
TI  - 2,2,2-Trifluoroethyl 6-thio-beta-D-glucopyranoside as a selective tag for
      cysteines in proteins.
AB  - A synthetic route to a trifluoromethyl and thiol containing glucose derivative
      (2,2,2-trifluoroethyl 6-thio-beta-D-glucopyranoside) is presented, which is based
      on microwave-assisted Fischer glycosylation under increased pressure. This water
      soluble, neutral thiol-compound can be used to selectively introduce a fluorine
      probe for (19)F NMR spectroscopy on cysteines in proteins. It can be attached
      under mild conditions in an aqueous environment without the risk of denaturing
      the protein. This tag has been applied to determine the redox-state of two
      cysteine residues in a bacterial transcription activator. Qualitative information
      about the solvent accessibility can be obtained from F-19 solvent PREs.

PMID- 23000217
TI  - Secretome analysis of Ganoderma lucidum cultivated in sugarcane bagasse.
AB  - Harmful environmental issues of fossil-fuels and concerns about petroleum
      supplies have spurred the search for renewable alternative fuels such as biofuel.
      Agricultural crop residues represent an abundant renewable resource for future
      biofuel. To be a viable alternative, a biofuel should provide a net energy gain,
      have environmental benefits, be economically feasible, and should also be
      producible in large quantities without reducing food supplies. We used these
      criteria to evaluate the white rot basidiomycota-derived fungus Ganoderma lucidum
      that secretes substantial amounts of hydrolytic and oxidative enzymes useful for
      the degradation of lignocellulosic biomass that were not described hitherto. The
      current bottleneck of lignocellulosic biofuel production is the hydrolysis of
      biomass to sugar. To understand the enzymatic hydrolysis of complex biomasses, we
      cultured G. lucidum with sugarcane bagasse as substrate and qualitatively
      analyzed the entire secretome. The secreted lignocellulolytic enzymes were
      identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and
      diverse enzymes were found, of which several were novel lignocellulosic biomass
      hydrolyzing enzymes. We further explored G. lucidum-derived cellulose,
      hemicellulose and lignin degrading enzymes as valuable enzymes for the second
      generation of biofuel obtained from a lignocellulose substrate such as sugarcane
      bagasse.

PMID- 23000218
TI  - Molecular targets of antimicrobial photodynamic therapy identified by a proteomic
      approach.
AB  - Antimicrobial photodynamic therapy (PDT) is a promising tool to combat antibiotic
      resistant bacterial infections. During PDT, bacteria are killed by reactive
      oxygen species generated by a visible light absorbing photosensitizer (PS). We
      used a classical proteomic approach that included two-dimensional gel
      electrophoresis and mass spectrometry analysis, to identify some proteins of
      Staphylococcus aureus that are damaged during PDT with the cationic PS meso-tetra
      4-N-methyl pyridyl porphine (T4). Suspensions of S. aureus cells were incubated
      with selected T4 concentrations and irradiated with doses of blue light that
      reduced the survival to about 60% or 1%. Proteomics analyses of a membrane
      proteins enriched fraction revealed that these sub-lethal PDT treatments affected
      the expression of several functional classes of proteins, and that this damage is
      selective. Most of these proteins were found to be involved in metabolic
      activities, in oxidative stress response, in cell division and in the uptake of
      sugar. Subsequent analyses revealed that PDT treatments delayed the growth and
      considerably reduced the glucose consumption capacity of S. aureus cells. This
      investigation provides new insights towards the characterization of PDT induced
      damage and mechanism of bacterial killing using, for the first time, a proteomic
      approach.

PMID- 23000219
TI  - Identification of mycobacterial membrane proteins and their types using over
      represented tripeptide compositions.
AB  - Mycobacterium can cause many serious diseases, such as tuberculosis and leprosy.
      Its membrane proteins play a critical role for multidrug-resistance and its
      tenacious survival ability. Knowing the types of membrane proteins will provide
      novel insights into understanding their functions and facilitate drug target
      discovery. In this study, a novel method was developed for predicting
      mycobacterial membrane protein and their types by using over-represented
      tripeptides. A total of 295 non-membrane proteins and 274 membrane proteins were
      collected to evaluate the performance of proposed method. The results of
      jackknife cross-validation test show that our method achieves an overall accuracy
      of 93.0% in discriminating between mycobacterial membrane proteins and
      mycobacterial non-membrane proteins and an overall accuracy of 93.1% in
      classifying mycobacterial membrane protein types. By comparing with other
      methods, the proposed method showed excellent predictive performance. Based on
      the proposed method, we built a predictor, called MycoMemSVM, which is freely
      available at http://lin.uestc.edu.cn/server/MycoMemSVM. It is anticipated that
      MycoMemSVM will become a useful tool for the annotation of mycobacterial membrane
      proteins and the development of anti-mycobacterium drug design.

PMID- 23000220
TI  - Seroprevalence of poliovirus antibodies amongst children in Zaria, Northern
      Nigeria.
AB  - BACKGROUND: Poliomyelitis is endemic in Northern Nigeria where there is
      continuous transmission of wild poliovirus 1 and 3 (WPV1 and 3) and circulating
      vaccine derived poliovirus 2 (cVDPV2) resulting in a high number of cases of
      children with acute flaccid paralysis. The seroprevalence of antibodies to polio
      serotypes which can be used to assess the immune status of children and the
      effectiveness of the vaccine against poliomyelitis is unknown, despite its
      endemicity in this part of the world. OBJECTIVE: This study aimed to determine
      the seroprevalence of poliovirus antibodies in children aged 1-10 years in Zaria,
      Northern Nigeria. METHODS: A descriptive, cross sectional, community based study
      was undertaken in Zaria, North Western Nigeria between 2008 and 2009. Two hundred
      and sixty-four (264) children aged 1-10 years were enrolled from two local
      government in Zaria by multistage random sampling method. Demographic data and
      polio immunisation history were retrieved from parents and caregivers by an
      interviewer administered questionnaire. Neutralising antibody titres to
      polioserotypes 1, 2 and 3 were assayed according to the WHO Manual for the
      virological investigation of polio. Antibody titres >= 1:8 were considered
      positive. RESULTS: The mean age of the 264 children studied was 6.25 years. Fifty
      five percent of the children were protected against the three polioserotypes,
      while 86.4%, 76.1% and 77.3% of children had neutralising antibodies to P1, P2
      and P3 polioserotypes respectively. 5 (1.9%) of the children had no antibodies to
      all the three polioserotypes. Polio antibody seropositivity was significantly
      associated with higher socioeconomic status and immunisation was the single most
      important determinant of seropositivity to poliovirus serotypes. CONCLUSION:
      Seroprevalence to poliovirus serotypes, though higher than values found in
      previous studies done in Nigeria, was lower compared to findings in the developed
      world. The use of more immunogenic vaccines and the balanced use of OPV
      formulations in SIAs, with further improvements in programme quality could
      provide the necessary immune booster to make polio eradication in Nigeria a
      reality.

PMID- 23000222
TI  - Immune response and protective efficacy of live attenuated Salmonella vaccine
      expressing antigens of Mycobacterium avium subsp. paratuberculosis against
      challenge in mice.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic granulomatous
      enteritis in ruminants that leads to diarrhea and eventually death. Existing
      vaccines have proven useful in limiting disease progression but have not been
      effective in preventing infection. To address this problem we constructed an
      attenuated Salmonella (DeltayejE; DeltassaV) strain harboring a plasmid that
      expressed a fusion protein comprised of the Salmonella Type III secretion system
      (T3SS) effector SopE and MAP antigens (85A, 85B, SOD, 74F) and evaluated its
      potential as vaccine candidate against MAP infection in mice. Of various SopE-MAP
      fusion proteins analyzed, only SopE104-Ag85A C-terminal(202-347)-SOD N-terminal(1
      72)-Ag85B C-terminal(173-330) and SopE104-74F(1-148+669-786)were successfully
      expressed and secreted into culture media as revealed by western blot analysis.
      Mice immunized with attenuated Salmonella (DeltayejE; DeltassaV) harboring the
      SopE104-Ag85A C-terminal(202-347)-SOD N-terminal(1-72)-Ag85B C-terminal(173-330)
      and SopE104-74F(1-148+669-786)plasmid generated a potent and long lasting Th1
      response characterized by production of IFN-gamma. The cytokine profile varied at
      various time points after immunization and challenge, which showed down
      regulation of Th2 cytokines (IL-4, IL-10) and up-regulation of proinflammatory
      cytokines (IL-12 and IL-17). Further, the immune response correlated with
      protection as revealed by reduced bacterial load and improved histopathology of
      spleen and liver, which showed fewer granulomas and lower numbers of acid-fast
      bacilli as compared to PBS controls. Interestingly, vaccination with antigens
      mixed with Ribi adjuvant (Agmix+Ribi) imparted better protection than the
      attenuated salmonella vectored vaccine. Thus, priming with a live recombinant
      Salmonella strain that secretes MAP antigens represents a promising approach that
      could lead to development of an efficacious and cost effective vaccine for
      Johne's disease.

PMID- 23000221
TI  - Role of antibody dependent cell mediated cytotoxicity (ADCC) in Sm-p80-mediated
      protection against Schistosoma mansoni.
AB  - Schistosomiasis is a major health problem in the developing world and for
      international travelers to the endemic countries. Existing strategies to control
      schistosomiasis have had limited successes so far. The addition of an effective
      vaccine in existing control measures would be greatly beneficial in reducing the
      impact of the disease. In this regard, Sm-p80 mediated protection against
      intestinal schistosomiasis caused by Schistosoma mansoni has been observed to be
      promising in two animal models of infection and disease. In this study, the role
      of antibody dependent cell mediated cytotoxicity (ADCC) was deciphered in Sm-p80
      mediated protection especially in the elimination of lung stage schistosomula.
      This was achieved using lung lavage cells and lung cells that were isolated from
      mice immunized with and without Sm-p80 formulated in a recombinant vaccine
      formulation. Significant differences were observed in cytotoxicity assays using
      immune sera with the lung lavage cells which showed 51% more killing of
      schistosomula and elevated levels of nitric oxide in the supernatants were
      detected compared to controls.

PMID- 23000223
TI  - The cost-effectiveness of pentavalent rotavirus vaccination in England and Wales.
AB  - Rotavirus vaccines have shown great potential for reducing the disease burden of
      the major cause of severe childhood gastroenteritis. The decision regarding
      whether rotavirus vaccination will be introduced into the national immunization
      program is currently being reviewed. The conclusions of previous evaluations of
      rotavirus vaccination cost-effectiveness contradict each other. This is the first
      analysis to incorporate a dynamic transmission model to assess the cost
      effectiveness of rotavirus vaccination in England and Wales. Most previously
      reported models do not include herd protection, and thus may underestimate the
      cost-effectiveness of vaccination against rotavirus. We incorporate a dynamic
      model of rotavirus transmission in England and Wales into a cost-effectiveness
      analysis to determine the probability that the pentavalent rotavirus vaccination
      will be cost-effective over a range of full-course vaccine prices. This novel
      approach allows the cost-effectiveness analysis to include a feasible level of
      herd protection provided by a vaccination program. Our base case model predicts
      that pentavalent rotavirus vaccination is likely to be cost-effective in England
      and Wales at L 60 per course. In some scenarios the vaccination is predicted to
      be not only cost-effective but also cost-saving. These savings could be generated
      within ten years after vaccine introduction. Our budget impact analysis
      demonstrates that for the realistic base case scenarios, 58-96% of the cost
      outlay for vaccination will be recouped within the first four years of a program.
      Our results indicate that rotavirus vaccination would be beneficial to public
      health and could be economically sound. Since rotavirus vaccination is not
      presently on the immunization schedule for England and Wales but is currently
      under review, this study can inform policymakers of the cost-effectiveness and
      budget impact of implementing a mass rotavirus vaccine strategy.

PMID- 23000224
TI  - Rectal indomethacin for the prevention of post-ERCP pancreatitis: a valuable tool
      to keep in your back pocket.

PMID- 23000225
TI  - Relative or relevant risk?

PMID- 23000226
TI  - Recurrent somatic mutations in human gastric cancers identified by whole exome
      sequencing.

PMID- 23000227
TI  - Cell shedding: old questions answered.

PMID- 23000228
TI  - Prophylactic anticoagulation in cirrhotics: a paradox for prime time?

PMID- 23000229
TI  - Lymphotoxin in the pathogenesis of autoimmune pancreatitis: a new player in the
      field.

PMID- 23000230
TI  - Regulatory T-cell therapy for Crohn's disease: in vivo veritas.

PMID- 23000231
TI  - Multiple cystic tumors throughout the abdominal and pelvic cavity.

PMID- 23000232
TI  - A rare cause of dysphagia in an elderly patient.

PMID- 23000233
TI  - An 18-year-old woman with a 15-cm liver mass and an ammonia level of 342.

PMID- 23000234
TI  - Piperaquine phosphate: reproduction studies.
AB  - In embryofetal studies in rat and rabbit Piperaquine phosphate (PQP) was not
      teratogenic at the maximal tolerated dose, even in presence of fetal exposure. In
      peri- post-natal study in rat, PQP did not interfere with the course of delivery
      at the dose of 5 mg/kg/day (treatment Gestation Day(GD)6-Lactation Day(LD)21) as
      well as up to the dose of 20 mg/kg/day (treatment GD6-17 and LD1-21). PQP at the
      dose of 80 mg/kg, induced prolonged gestation, dystocic delivery and increase
      perinatal mortality both with interruption of treatment (GD6 to GD17 and LD1-21)
      and with continuous dosing (GD19-LD21). PQP did not interfere with lactation and
      pup growth and development, in presence of clear exposure during suckling period,
      irrespective of the dose and treatment schedules. It was not possible to identify
      the mechanism leading to the delivery delay. In a comparative study using other
      antimalarials, only Mefloquine gave similar findings to PQP.

PMID- 23000235
TI  - Estimation of spatio-temporal parameters for post-stroke hemiparetic gait using
      inertial sensors.
AB  - This paper represents the first step in developing an inertial sensor system that
      is capable of assessing post-stroke gait in terms of walking speed and temporal
      gait symmetry. Two inertial sensors were attached at the midpoint of each shank
      to measure the accelerations and angular velocity during walking. Despite the
      abnormalities in hemiparetic gait, the angular velocity of most of the testing
      subjects (12 out of 13) exhibited similar characteristics as those from a healthy
      population, enabling walking speed estimation and gait event detection based on
      the pendulum walking model. The results from a standardized 10-meter walk test
      demonstrated that the IMU-based method has an excellent agreement with the
      clinically used stopwatch method. The gait symmetry results were comparable with
      previous studies. The gait segmentation failed when the angular velocity deviates
      significantly from the healthy groups' profile. With further development and
      concurrent validations, the inertial sensor-based system may eventually become a
      useful tool for continually monitoring spatio-temporal gait parameters post
      stroke in a natural environment.

PMID- 23000236
TI  - Emergence of tigecycline-resistant Klebsiella pneumoniae after tigecycline
      therapy for complicated urinary tract infection caused by carbapenem-resistant
      Escherichia coli.

PMID- 23000237
TI  - Radioembolization for hepatocellular carcinoma with portal vein thrombosis:
      impact of liver function on systemic treatment options at disease progression.
AB  - BACKGROUND & AIMS: Yttrium-90 ((90)Y) radioembolization is a microembolic
      procedure. Hence, it is commonly used in hepatocellular carcinoma (HCC) patients
      with portal venous thrombosis (PVT). We analyzed liver function, imaging
      findings, and treatment options (local/systemic) at disease progression following
      (90)Y treatment in HCC patients with PVT. METHODS: We treated 291 HCC patients
      with (90)Y radioembolization. From this cohort, we included patients with liver
      only disease, PVT and Child-Pugh (CP) score <= 7; this identified 63 patients
      with HCC and PVT (CP-A:35, CP-B7:27). Liver function, CP status, and imaging
      findings at progression were determined in order to assess potential candidacy
      for systemic treatment/clinical trials. Survival, time-to-progression (TTP), and
      time-to-hepatic decompensation analyses were performed using Kaplan-Meier
      methodology. RESULTS: Of 35 CP-A and 28 CP-B7 patients, 29 and 15 progressed,
      respectively. Median survival and TTP were 13.8 and 5.6 months in CP-A and 6.5
      and 4.9 months in CP-B7 patients, respectively. Of the 29 CP-A patients who
      progressed, 45% maintained their CP status at progression (55% decompensated to
      CP-B). Of the 15 CP-B7 patients who progressed, 20% improved to CP-A, 20%
      maintained their CP score and 60% decompensated. CONCLUSIONS: Knowledge of liver
      function and CP score of HCC with PVT progressing after (90)Y is critically
      relevant information, as these patients may be considered for systemic
      therapy/clinical trials. If a strict CP-A status is mandated, our study
      demonstrated that 64% of cases exhibited inadequate liver function and were
      ineligible for systemic therapy/clinical trials. An adjuvant approach using local
      therapy and systemic agents prior to progression should be investigated.

PMID- 23000238
TI  - Emerging micro- and nanotechnologies at the interface of engineering, science,
      and medicine for the development of novel drug delivery devices and systems.
      (Preface).

PMID- 23000239
TI  - Overview of the impact of kisspeptin on reproductive function.
AB  - Since 2003, kisspeptin and its receptor (KISS1R, also called GPR54) are
      recognized as major actors of the gonadotrope axis. Mutations of genes encoding
      the peptide or the receptor have been identified in patients with precocious
      puberty or hypogonadotropic hypogonadism. They are strong stimulators of GnRH
      neurons and are involved in various mechanisms regulating gonadotrope axis as
      puberty induction or positive and negative feedback regulation on the gonadotrope
      axis by gonadal steroids. They also mediated some metabolic or environmental
      signals on the reproduction axis. Kisspeptins are synthesized and secreted by
      hypothalamic nuclei located in the arcuate nucleus (ARC) and anteroventral
      periventricular nucleus (AVPV). This system is complex because neurons located in
      the ARC coexpress many neuromediators such as neurokinin B and dynorphin,
      involved in the control of gonadotrope axis. During pregnancy, kisspeptins are
      also secreted by placenta and should be involved in trophoblastic invasion. After
      kisspeptin administration to male and female animals as well as to women with
      hypothalamic secondary amenorrhoea, they are able to stimulate GnRH and
      gonadotrophin secretion. Then, kisspeptin agonists appear as valuable new tools
      in treatment for reproduction troubles. The aim of this review is to clarify the
      role of kisspeptins in regulating gonadotrophin secretion and explores their
      possible therapeutic use.

PMID- 23000240
TI  - Phenomenological and spectroscopic analysis on the effects of sediment ageing and
      organic carbon on the fate of a PCB congener spiked to sediment.
AB  - This study assesses the full cycle transport and fate of a polychlorinated
      biphenyl (PCB) congener spiked to sediment to empirically and spectroscopically
      investigate the effects of sediment ageing and organic carbon on the adsorption,
      desorption, and reaction of the PCB. Caesar Creek sediment (CCS) was oxidized to
      remove amorphous organic carbon (AOC) followed by soot carbon (SC), spiked and
      aged with 2-chlorobiphenyl (2-ClBP), mixed with various aquatic solutions, and
      treated on reactive activated carbon (RAC) impregnated with palladized iron.
      Results showed that 2-ClBP sorption isotherms and kinetic parameters well
      reflected the critical influence of AOC and SC on the sorption behavior of 2
      ClBP. Infrared analysis implied the presence of preferred 2-ClBP sorption sites
      within the sediment matrix. The shift in the CH vibrational frequencies of 2-ClBP
      bound to CCS was more apparent in cases of higher organic content (particularly
      SC) and longer ageing time, which made 2-ClBP more sorbed and strongly bound to
      CCS and thus made it more difficult to desorb 2-ClBP. The ageing effect on 2-ClBP
      binding was more prominent in the presence of organic carbon. Only desorbed 2
      ClBP was transported to the target RAC for its physical adsorption and chemical
      dechlorination.

PMID- 23000241
TI  - Adsorption of arsenate on Cu/Mg/Fe/La layered double hydroxide from aqueous
      solutions.
AB  - A novel layered double hydroxide containing lanthanum (Cu/Mg/Fe/La-LDH) has been
      synthesized and used for the removal of arsenate from aqueous solutions. The
      purpose of incorporation of La3+ into LDHs was tried to enhance the uptake
      efficiency of arsenate and broaden the application field of LDHs functional
      materials. Effects of various physico-chemical factors such as solution pH,
      adsorbent dosage, contact time and initial arsenate concentrations on the
      adsorption of arsenate onto Cu/Mg/Fe/La-LDH were investigated. Results showed
      that the removal efficiency of arsenate increased with the increment of the
      lanthanum content in Cu/Mg/Fe/La-LDH adsorbents, and the optimized lanthanum
      content was 20% of the total trivalent metals composition (Fe3+ and La3+). The
      adsorption isotherms can be well described by Langmuir equation, and the
      adsorption kinetics of arsenate followed the pseudo-second-order kinetic model.
      Coexistent ions such as HPO4(2-), CO3(2-), SO4(2-), Cl- and NO3- exhibited
      obvious competition with arsenate for the adsorption on Cu/Mg/Fe/La-LDH. The
      solution pH significantly affected the removal efficiency, which was closely
      related to the change of arsenate species distribution under different pH
      conditions. The predominant adsorption mechanism can be mainly attributed to the
      processes including ion exchange and layer ligand exchange.

PMID- 23000242
TI  - Simple and sensitive assay for quantification of oseltamivir and its active
      metabolite oseltamivir carboxylate in human plasma using high-performance liquid
      chromatography coupled with electrospray ionization tandem mass spectrometry:
      improved applicability to pharmacokinetic study.
AB  - Although liquid chromatography/electrospray ionization tandem mass spectrometry
      based assays have been reported for the measurement of the antiviral oseltamivir
      (OS) in human samples, these assays either involve complicated sample
      pretreatment or lack sensitivity. Here we introduce a straightforward approach to
      improve the assay performance for OS and its metabolite oseltamivir carboxylate
      (OSC) in human plasma. A very low concentration of mobile phase modifier can
      improve the ionization efficiency of both analytes, thus enabling a high
      sensitivity without any matrix effect. The fast LC gradient further increases the
      sensitivity by narrowing the peak width (6-9s) and eluting the analytes at higher
      organic content. The increased ionization efficiency and minimized matrix effects
      enabled us to introduce a one-step protein precipitation for sample clean-up
      without compromising the sensitivity. The lower limit of quantification was 0.34
      ng/mL for both analytes, which was at least 3 times more sensitive than published
      assays that involve complicated sample pretreatment. The assay involves
      measurement of analytes and their stable-isotope internal standards in small
      volume (30-MUL) plasma. Sodium fluoride was utilized to prevent the hydrolysis of
      OS during and after sampling. The calibration curve was linear over the range of
      0.34-1000 ng/mL. Accuracy was 95-110% and the precision was 2.2-11.0%. This
      method was applied successfully to the human pharmacokinetic study of OS, and can
      estimate the relevant pharmacokinetic parameters of OS with more accuracy. The
      approach utilized in the optimization of assay performance can be extended to the
      measurement of other drugs in biomatrices.

PMID- 23000243
TI  - Oxidative stress and nitrosative stress are involved in different stages of
      proteolytic pulmonary emphysema.
AB  - Our aim was to investigate the role of oxidative stress in elastase-induced
      pulmonary emphysema. C57BL/6 mice were subjected to pancreatic porcine elastase
      (PPE) instillation (0.05 or 0.5 U per mouse, i.t.) to induce pulmonary emphysema.
      Lungs were collected on days 7, 14, and 21 after PPE instillation. The control
      group was sham injected. Also, mice treated with 1% aminoguanidine (AMG) and
      inducible NO synthase (iNOS) knockout mice received 0.5 U PPE (i.t.), and lungs
      were analyzed 21 days after. We performed bronchoalveolar lavage, biochemical
      analyses of oxidative stress, and lung stereology and morphometry assays.
      Emphysema was observed histologically at 21 days after 0.5 U PPE treatment;
      tissues from these mice exhibited increased alveolar linear intercept and air
      space volume density in comparison with the control group. TNF-alpha was elevated
      at 7 and 14 days after 0.5 U PPE treatment, concomitant with a reduction in the
      IL-10 levels at the same time points. Myeloperoxidase was elevated in all groups
      treated with 0.5 U PPE. Oxidative stress was observed during early stages of
      emphysema, with increased nitrite levels and malondialdehyde and superoxide
      dismutase activity at 7 days after 0.5 U PPE treatment. Glutathione peroxidase
      activity was increased in all groups treated with 0.5 U PPE. The emphysema was
      attenuated when iNOS was inhibited using 1% AMG and in iNOS knockout mice.
      Furthermore, proteolytic stimulation by PPE enhanced the expression of
      nitrotyrosine and iNOS, whereas the PPE+AMG group showed low expression of iNOS
      and nitrotyrosine. PPE stimulus also induced endothelial (e) NOS expression,
      whereas AMG reduced eNOS. Our results suggest that the oxidative and nitrosative
      stress pathways are triggered by nitric oxide production via iNOS expression in
      pulmonary emphysema.

PMID- 23000244
TI  - Tetrathiatriarylmethyl radical with a single aromatic hydrogen as a highly
      sensitive and specific superoxide probe.
AB  - Superoxide (O(2)(*-)) plays crucial roles in normal physiology and disease;
      however, its measurement remains challenging because of the limited sensitivity
      and/or specificity of prior detection methods. We demonstrate that a
      tetrathiatriarylmethyl (TAM) radical with a single aromatic hydrogen (CT02-H) can
      serve as a highly sensitive and specific O(2)(*-) probe. CT02-H is an analogue of
      the fully substituted TAM radical CT-03 (Finland trityl) with an electron
      paramagnetic resonance (EPR) doublet signal due to its aromatic hydrogen. Owing
      to the neutral nature and negligible steric hindrance of the hydrogen, O(2)(*-)
      preferentially reacts with CT02-H at this site with production of the diamagnetic
      quinone methide via oxidative dehydrogenation. Upon reaction with O(2)(*-), CT02
      H loses its EPR signal and this EPR signal decay can be used to quantitatively
      measure O(2)(*-). This is accompanied by a change in color from green to purple,
      with the quinone methide product exhibiting a unique UV-Vis absorbance
      (epsilon=15,900 M(-1) cm(-1)) at 540 nm, providing an additional O(2)(*-)
      detection method. More than five-fold higher reactivity of CT02-H for O(2)(*-)
      relative to CT-03 was demonstrated, with a second-order rate constant of
      1.7*10(4) M(-1) s(-1) compared to 3.1*10(3) M(-1) s(-1) for CT-03. CT02-H
      exhibited high specificity for O(2)(*-) as evidenced by its inertness to other
      oxidoreductants. The O(2)(*-) generation rates detected by CT02-H from
      xanthine/xanthine oxidase were consistent with those measured by cytochrome c
      reduction but detection sensitivity was 10- to 100-fold higher. EPR detection of
      CT02-H enabled measurement of very low O(2)(*-) flux with a detection limit of
      0.34 nM/min over 120 min. HPLC in tandem with electrochemical detection was used
      to quantitatively detect the stable quinone methide product and is a highly
      sensitive and specific method for measurement of O(2)(*-), with a sensitivity
      limit of ~2*10(-13) mol (10 nM with 20-MUl injection volume). Based on the O(2)
      dependent linewidth broadening of its EPR spectrum, CT02-H also enables
      simultaneous measurement of O(2) concentration and O(2)(*-) generation and was
      shown to provide sensitive detection of extracellular O(2)(*-) generation in
      endothelial cells stimulated either by menadione or with anoxia/reoxygenation.
      Thus, CT02-H is a unique probe that provides very high sensitivity and
      specificity for measurement of O(2)(*-) by either EPR or HPLC methods.

PMID- 23000246
TI  - Oxidative stress, neurodegeneration, and the balance of protein degradation and
      protein synthesis.
AB  - Oxidative stress occurs in a variety of disease settings and is strongly linked
      to the development of neuron death and neuronal dysfunction. Cells are equipped
      with numerous pathways to prevent the genesis, as well as the consequences, of
      oxidative stress in the brain. In this review we discuss the various forms and
      sources of oxidative stress in the brain and briefly discuss some of the
      complexities in detecting the presence of oxidative stress. We then focus the
      review on the interplay between the diverse cellular proteolytic pathways and
      their roles in regulating oxidative stress in the brain. Additionally, we discuss
      the involvement of protein synthesis in regulating the downstream effects of
      oxidative stress. Together, these components of the review demonstrate that the
      removal of damaged proteins by effective proteolysis and the synthesis of new and
      protective proteins are vital in the preservation of brain homeostasis during
      periods of increased levels of reactive oxygen species. Last, studies from our
      laboratory and others have demonstrated that protein synthesis is intricately
      linked to the rates of protein degradation, with impairment of protein
      degradation sufficient to decrease the rates of protein synthesis, which has
      important implications for successfully responding to periods of oxidative
      stress. Specific neurodegenerative diseases, including Alzheimer disease,
      Parkinson disease, amyotrophic lateral sclerosis, and stroke, are discussed in
      this context. Taken together, these findings add to our understanding of how
      oxidative stress is effectively managed in the healthy brain and help elucidate
      how impairments in proteolysis and/or protein synthesis contribute to the
      development of neurodegeneration and neuronal dysfunction in a variety of
      clinical settings. 

PMID- 23000247
TI  - A novel small molecule, N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6
      trimethylphenoxy) acetamide, selectively protects against oxidative stress
      induced cell death by activating the Nrf2-ARE pathway: therapeutic implications
      for ALS.
AB  - Antioxidant defense is crucial in restoring cellular redox homeostasis. Recent
      findings have suggested that oxidative stress plays pivotal roles in the
      pathogenesis of many neurodegenerative diseases. Thus, an anti-oxidative stress
      remedy might be a promising means for the treatment of such disorders. In this
      study, we employed a novel ligand-based virtual screening system and identified a
      novel small molecule, N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6
      trimethylphenoxy) acetamide (CPN-9), which selectively suppressed oxidative
      stress-induced cell death in a cell-type-independent manner. CPN-9 upregulates NF
      E2-related factor 2 (Nrf2), a key transcriptional regulator of the expression of
      phase II detoxification enzymes and antioxidant proteins, and Nrf2-regulated
      factors such as heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1),
      and glutamate-cysteine ligase modifier subunit (GCLM). The CPN-9-mediated
      upregulation of HO-1, NQO1, and GCLM was abolished by Nrf2 knockdown. Moreover,
      the antioxidant N-acetylcysteine reduced the protective effect of CPN-9 against
      oxidative stress-induced cell death with concomitant diminishing of Nrf2 nuclear
      translocation. These results indicate that CPN-9 exerts its activity via the
      reactive oxygen species-dependent activation of the Nrf2 signaling pathway in
      cultured cells. It is noteworthy that the postonset systemic administration of
      CPN-9 to a transgenic ALS mouse model carrying the H46R mutation in the human
      Cu/Zn superoxide dismutase (SOD1) gene sustained motor functions and delayed
      disease progression after onset. Collectively, CPN-9 is a novel Nrf2 activator
      and a neuroprotective candidate for the treatment of neurodegenerative diseases,
      including ALS.

PMID- 23000248
TI  - Conformational dynamics of the interaction of Escherichia coli endonuclease VIII
      with DNA substrates.
AB  - Endonuclease VIII (Nei) from Escherichia coli is a DNA repair enzyme that removes
      a wide range of oxidized pyrimidine bases from DNA. As inferred from the crystal
      structures and biochemical studies, recognition of DNA lesions by Nei involves
      several conformational changes in both protein and DNA, such as DNA kinking,
      damaged base eversion into the enzyme's active site, and insertion of a loop of
      the enzyme into the void formed by the eversion. Excision of the damaged base by
      Nei also proceeds through several chemical steps: N-glycosidic bond breakage,
      beta-elimination and delta-elimination of the phosphates flanking the lesion. We
      have used stopped-flow kinetics with fluorescence detection to follow
      conformational changes in the Nei molecule when the enzyme binds normal DNA,
      damaged but uncleavable DNA, or several cleavable damaged DNA substrates. Binding
      normal or damaged uncleavable DNA proceeded in two fluorescently discernible
      reversible stages, while processing of cleavable substrates involved three
      reversible stages followed by and irreversible stage and equilibrium with the
      reaction product. Individual rate constants were calculated for each reaction
      step. Based on the stopped-flow data, crystal structure, and a comparison with
      the stopped-flow kinetics of E. coli formamidopyrimidine-DNA glycosylase, a
      homolog of Nei, we propose the nature of some of the steps that may be involved
      into the recognition and excision of damaged bases by Nei.

PMID- 23000245
TI  - Redox regulation of mitochondrial biogenesis.
AB  - The cell renews, adapts, or expands its mitochondrial population during episodes
      of cell damage or periods of intensified energy demand by the induction of
      mitochondrial biogenesis. This bigenomic program is modulated by redox-sensitive
      signals that respond to physiological nitric oxide (NO), carbon monoxide (CO),
      and mitochondrial reactive oxygen species production. This review summarizes our
      current ideas about the pathways involved in the activation of mitochondrial
      biogenesis by the physiological gases leading to changes in the redox milieu of
      the cell, with an emphasis on the responses to oxidative stress and inflammation.
      The cell's energy supply is protected from conditions that damage mitochondria by
      an inducible transcriptional program of mitochondrial biogenesis that operates in
      large part through redox signals involving the nitric oxide synthase and the heme
      oxygenase-1/CO systems. These redox events stimulate the coordinated activities
      of several multifunctional transcription factors and coactivators also involved
      in the elimination of defective mitochondria and the expression of
      counterinflammatory and antioxidant genes, such as IL10 and SOD2, as part of a
      unified damage-control network. The redox-regulated mechanisms of mitochondrial
      biogenesis schematically outlined in the graphical abstract link mitochondrial
      quality control to an enhanced capacity to support the cell's metabolic needs
      while improving its resistance to metabolic failure and avoidance of cell death
      during periods of oxidative stress.

PMID- 23000249
TI  - Snake venom metalloproteinases.
AB  - Recent proteomic analyses of snake venoms show that metalloproteinases represent
      major components in most of the Crotalid and Viperid venoms. In this chapter we
      discuss the multiple activities of the SVMPs. In addition to hemorrhagic
      activity, members of the SVMP family also have fibrin(ogen)olytic activity, act
      as prothrombin activators, activate blood coagulation factor X, possess apoptotic
      activity, inhibit platelet aggregation, are pro-inflammatory and inactivate blood
      serine proteinase inhibitors. Clearly the SVMPs have multiple functions in
      addition to their well-known hemorrhagic activity. The realization that there are
      structural variations in the SVMPs and the early studies that led to their
      classification represents an important event in our understanding of the
      structural forms of the SVMPs. The SVMPs were subdivided into the P-I, P-II and P
      III protein classes. The noticeable characteristic that distinguished the
      different classes was their size (molecular weight) differences and domain
      structure: Class I (P-I), the small SVMPs, have molecular masses of 20-30 kDa,
      contain only a pro domain and the proteinase domain; Class II (P-II), the medium
      size SVMPs, molecular masses of 30-60 kDa, contain the pro domain, proteinase
      domain and disintegrin domain; Class III (P-III), the large SVMPs, have molecular
      masses of 60-100 kDa, contain pro, proteinase, disintegrin-like and cysteine-rich
      domain structure. Another significant advance in the SVMP field was the
      characterization of the crystal structure of the first P-I class SVMP. The
      structures of other P-I SVMPs soon followed and the structures of P-III SVMPs
      have also been determined. The active site of the metalloproteinase domain has a
      consensus HEXXHXXGXXHD sequence and a Met-turn. The "Met-turn" structure contains
      a conserved Met residue that forms a hydrophobic basement for the three zinc
      binding histidines in the consensus sequence.

PMID- 23000250
TI  - Three-finger toxins, a deadly weapon of elapid venom--milestones of discovery.
AB  - Three-finger toxins (TFTs) are the main venom components of snakes from Elapidae
      family. Amino acid sequences of more than five hundreds TFTs are determined;
      these toxins form one of the largest protein families present in snake venoms.
      The first TFT alpha-bungarotoxin was isolated almost half a century ago and so
      far it remains a valuable tool in the study of nicotinic acetylcholine receptors.
      TFTs possess diverse biological activities; for example, alpha-neurotoxins bind
      specifically with high affinity to nicotinic acetylcholine receptors, while
      cytotoxins induce non-specific lysis in great variety of cells. These toxins are
      widely used as instruments in different branches of life sciences. In this review
      the main landmarks in TFT study are considered. These are the discovery and
      isolation of TFTs, determination of their structure and mode of action as well as
      evolution and relationship within the family.

PMID- 23000251
TI  - Bioconversion of quercetin and rutin and the cytotoxicity activities of the
      transformed products.
AB  - Quercetin and rutin are well-know flavonoids. In spite of this, the comprehension
      of their metabolism is still incomplete. In this work, the cytotoxic activity of
      quercetin and rutin and its metabolites produced by metabolism of filamentous
      fungi was investigated. Flavonoids metabolism was monitored by HPLC and LC-MS.
      Both flavonoids were extensively metabolized. Quercetin was converted into
      metabolite methylquercetin (2) and quercetin glucuronide (3) and rutin into
      metabolite rutin sulphate (5), methylrutin (6) and rutin glucuronide (7).
      Cytotoxic effects of rutin, quercetin and its metabolites were measured by MTT
      tetrazolium reduction test and the trypan blue exclusion assay on HL-60 leukemic
      cells. The results showed similar concentration-dependent cytotoxic effect for
      rutin and rutin sulphate (5), while no cytotoxic effect was detected with the
      metabolites 6 and 7. In relation to the quercetin and its metabolites the results
      showed that all compounds have a similar concentration-dependent inhibitory
      effect on HL-60 cells. These findings corroborate the literature, showing that
      bioconversion is a useful strategy for production of biological active
      metabolites.

PMID- 23000252
TI  - The amino acid residue L113 is involved in arginine kinase activity and
      structural stability.
AB  - Arginine kinase (AK) catalyzes the reversible phosphorylation of arginine by ATP,
      yielding the phosphoarginine. Domain-domain interactions are important to the
      function of multidomain proteins. However, little is known about the role of the
      linker in the proteins folding, activity and structural stability. In this
      research, a series mutation of conserved residue L113 located in the linker was
      mutated to explore its roles in the activity and structural stability of AK. The
      mutations L113D and L113K led to pronounced loss of activity and structural
      stability. Furthermore, spectroscopic experiments indicated that the mutations
      L113D and L113K impaired the structure of AK, which resulted in a partially
      unfolded state with more hydrophobic exposure and exposed Trp residues. The
      inability to fold to the functional compact state made the mutant is prone to
      aggregate under environmental stresses. While the mutation L113I almost had no
      effect on AK activity and structural stability. These results suggested that the
      residue L113 played important roles in sustaining the N- and C-terminal domains
      interactions.

PMID- 23000253
TI  - Chemical, structural and thermal properties of Gonometa postica silk fibroin, a
      potential biomaterial.
AB  - In the present study, chemical, structural and thermal properties of fibroin from
      Gonometa postica, a wild silkmoth species were investigated. Silk from Gonometa
      rufobrunnea and Bombyx mori species were included in this study for comparison.
      The results indicated that G. postica and G. rufobrunnea silk exhibited similar
      properties whereas distinct differences were observed with B. mori silk. Amino
      acid analysis showed that glycine, alanine and serine accounted for more than 70%
      of the total amino acid content in all species. The amount of polar amino acids
      in Gonometa fibroin was significantly higher than for B. mori fibroin suggesting
      increased chemical reactivity of the former. The abundance of basic amino acids
      in Gonometa fibroin makes it a promising biomaterial in cell and tissue culture.
      Structural analysis revealed a unique beta-sheet structure of Gonometa fibroin
      which is comprised of both poly-alanine and poly-glycine-alanine sequences. The
      maximum decomposition temperatures for Gonometa and B. mori fibroin were 350
      degrees C and 320 degrees C respectively. The influence of amino acid composition
      on structural and thermal properties of the silks is also discussed.

PMID- 23000254
TI  - A polysaccharide isolated from Pueraria lobata enhances maturation of murine
      dendritic cells.
AB  - Maturation of dendritic cells (DCs) is a critical factor for initiating the
      immune response. However, DC maturation is usually attenuated in the tumor
      microenvironment, which is an important immunological problem in DC-based
      immunotherapy against cancer. Here, we report the effect of a polysaccharide
      (PLP) isolated from Pueraria lobata on phenotypic and functional maturation of
      DCs. Phenotypic maturation was demonstrated by increased expression of CD40,
      CD86, and major histocompatibility complex I/II. PLP induced functional
      maturation of DCs, as shown by increased production of interleukin (IL)-12, IL
      1beta, and tumor necrosis factor-alpha, decreased antigen capture capacity, and
      enhanced allogenic T cell stimulation. In addition, PLP activated DCs generated
      from C3H/HeN mice with normal TLR4, but not DCs from C3H/HeJ mice with mutated
      TLR4, suggesting that the TLR4 is a membrane receptor of PLP. We showed that PLP
      increased ERK, JNK, and p38 mitogen-activated protein kinase phosphorylation, and
      nuclear translocation of the nuclear factor-kappaB p65 subunit, which are
      signaling molecules downstream of TLR4. These results indicate that PLP induced
      DC maturation through TLR4 signaling.

PMID- 23000255
TI  - Co-localizing linguistic and musical syntax with intracranial EEG.
AB  - Despite general agreement on shared syntactic resources in music and language,
      the neuroanatomical underpinnings of this overlap remain largely unexplored.
      While previous studies mainly considered frontal areas as supramodal grammar
      processors, the domain-general syntactic role of temporal areas has been so far
      neglected. Here we capitalized on the excellent spatial and temporal resolution
      of subdural EEG recordings to co-localize low-level syntactic processes in music
      and language in the temporal lobe in a within-subject design. We used Brain
      Surface Current Density mapping to localize and compare neural generators of the
      early negativities evoked by violations of phrase structure grammar in both music
      and spoken language. The results show that the processing of syntactic violations
      relies in both domains on bilateral temporo-fronto-parietal neural networks. We
      found considerable overlap of these networks in the superior temporal lobe, but
      also differences in the hemispheric timing and relative weighting of their fronto
      temporal constituents. While alluding to the dissimilarity in how shared neural
      resources may be configured depending on the musical or linguistic nature of the
      perceived stimulus, the combined data lend support for a co-localization of early
      musical and linguistic syntax processing in the temporal lobe.

PMID- 23000257
TI  - A fNIRS investigation of switching and inhibition during the modified Stroop task
      in younger and older adults.
AB  - Brain imaging studies have reported age-related differences in brain activation
      for attentional control functions, such as inhibition and task-switching.
      However, age-related differences in brain activation patterns in more than one
      attentional control task have rarely been studied in the same group of
      participants. In this study, younger and older adults completed a modified Stroop
      task with interference and switching conditions, using functional near infra-red
      spectroscopy. While interference did not reveal any significant activation of the
      prefrontal cortex in younger adults, switching produced an increased activation
      bilaterally in both the anterior dorsolateral prefrontal cortex (DLPFC) and the
      anterior ventrolateral prefrontal cortex (VLPFC). In older adults, an isolated
      right and left anterior DLPFC activation was observed even in the non-executive
      conditions of the Stroop task (color denomination) and the interference condition
      revealed activation mostly in the posterior left DLPFC and bilateral VLPFC with a
      small right anterior DLPFC component. Specific to older adults, switching induced
      an increased activation spread out bilaterally over the prefrontal cortex in the
      bilateral anterior DLPFC, the posterior left DLPFC and bilateral VLPFC. These
      results suggest that for both older and younger adults, inhibition and switching
      are associated with distinct patterns of prefrontal activation and that age
      related differences exist in these patterns such that prefrontal activation seems
      to be more spread out at different sites in older adults.

PMID- 23000256
TI  - Does variability in cognitive performance correlate with frontal brain volume?
AB  - Little is known about the neural correlates of within-person variability in
      cognitive performance. We investigated associations between regional brain
      volumes and trial-to-trial, block-to-block, and day-to-day variability in choice
      reaction time, and episodic and working memory accuracy. Healthy younger (n=25)
      and older (n=18) adults underwent 101 daily assessments of cognitive performance,
      and their regional brain volumes were measured manually on magnetic resonance
      images. Results showed that smaller prefrontal white matter volumes were
      associated with higher block-to-block variability in choice-reaction time
      performance, with a stronger association observed among older adults. Smaller
      volumes of the dorsolateral prefrontal cortex covaried with higher block-to-block
      variability in episodic memory (number-word pair) performance. This association
      was stronger for younger adults. The observed associations between variability
      and brain volume were not due to individual differences in mean performance.
      Trial-to-trial and day-to-day variability in cognitive performance were unrelated
      to regional brain volume. We thus report novel findings demonstrating that block
      by-block variability in cognitive performance is associated with integrity of the
      prefrontal regions and that between-person differences in different measures of
      variability of cognitive performance reflect different age-related constellations
      of behavioral and neural antecedents.

PMID- 23000258
TI  - Characterization of the blood-oxygen level-dependent (BOLD) response in cat
      auditory cortex using high-field fMRI.
AB  - Much of what is known about the cortical organization for audition in humans
      draws from studies of auditory cortex in the cat. However, these data build
      largely on electrophysiological recordings that are both highly invasive and
      provide less evidence concerning macroscopic patterns of brain activation.
      Optical imaging, using intrinsic signals or dyes, allows visualization of surface
      based activity but is also quite invasive. Functional magnetic resonance imaging
      (fMRI) overcomes these limitations by providing a large-scale perspective of
      distributed activity across the brain in a non-invasive manner. The present study
      used fMRI to characterize stimulus-evoked activity in auditory cortex of an
      anesthetized (ketamine/isoflurane) cat, focusing specifically on the blood-oxygen
      level-dependent (BOLD) signal time course. Functional images were acquired for
      adult cats in a 7 T MRI scanner. To determine the BOLD signal time course, we
      presented 1s broadband noise bursts between widely spaced scan acquisitions at
      randomized delays (1-12 s in 1s increments) prior to each scan. Baseline trials
      in which no stimulus was presented were also acquired. Our results indicate that
      the BOLD response peaks at about 3.5s in primary auditory cortex (AI) and at
      about 4.5 s in non-primary areas (AII, PAF) of cat auditory cortex. The observed
      peak latency is within the range reported for humans and non-human primates (3-4
      s). The time course of hemodynamic activity in cat auditory cortex also occurs on
      a comparatively shorter scale than in cat visual cortex. The results of this
      study will provide a foundation for future auditory fMRI studies in the cat to
      incorporate these hemodynamic response properties into appropriate analyses of
      cat auditory cortex.

PMID- 23000259
TI  - Interaction of a bacterial monorhamnolipid secreted by Pseudomonas aeruginosa
      MA01 with phosphatidylcholine model membranes.
AB  - This work presents a biophysical study on the interactions of a monorhamnolipid
      (monoRL) produced by Pseudomonas aeruginosa MA01 with model phosphatidylcholine
      membranes. The molecular characterization of the biological activities, including
      the modulation of phospholipid membranes structure, of this monoRL biosurfactant
      is of importance for the validation of this particular Pseudomonas aeruginosa
      strain as a useful biosurfactant producer. The marked amphiphilic structure of
      monoRL is expected to result in strong interactions with the phospholipid
      constituents of membrane bilayers. Incorporation of monoRL into DMPC completely
      abolished the pretransition, and the main gel to liquid-crystalline phase
      transition was progressively broadened and shifted to lower temperatures, as
      observed by differential scanning calorimetry. Partial phase diagrams for DPPC
      and DSPC indicated near-ideal behavior. However, the DMPC diagram indicated fluid
      phase immiscibility. X-ray diffraction showed and apparent increase in d-value
      for DPPC containing monoRL, which might be the result of an effective increase in
      the bilayer thickness, or in the thickness of the hydration layer between
      bilayers. FTIR indicated that interaction of monoRL with the phospholipid acyl
      chains did not result in a large additional disordering of the acyl chain region
      of the fluid bilayer. Analysis of the C=O stretching band of DPPC indicated an
      important effect of monoRL on the interfacial region of phosphatidylcholine
      bilayers, which might contribute to explain some of the biological activities of
      this glycolipid.

PMID- 23000260
TI  - Involvement of ferritin heavy chain in the preventive effect of metformin against
      doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin is a wide-spectrum chemotherapeutic agent, although a cumulative dose
      may cause cardiac damage and lead to heart failure. Doxorubicin cardiotoxicity is
      dependent on the intracellular iron pool and manifests itself by increasing
      oxidative stress. Our group has recently shown the ability of metformin, an oral
      antidiabetic with cardiovascular benefits, to protect cardiomyocytes from
      doxorubicin-induced damage. This work aimed to study whether metformin is able to
      modulate the expression of ferritin, the major intracellular iron storage
      protein, in cardiomyocytes and whether it is involved in their protection. The
      addition of metformin to adult mouse cardiomyocytes (HL-1 cell line) induced both
      gene and protein expression of the ferritin heavy chain (FHC) in a time-dependent
      manner. The silencing of FHC expression with siRNAs inhibited the ability of
      metformin to protect cardiomyocytes from doxorubicin-induced damage, in terms of
      the percentage of cell viability, the levels of reactive oxygen species, and the
      activity of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide
      dismutase). In addition, metformin induced the activation of NF-kappaB in HL-1
      cells, whereas preincubation with SN50, an inhibitor of NF-kappaB, blocked the
      upregulation of the FHC and the protective effect mediated by metformin. Taken
      together, these results provide new knowledge on the protective actions of
      metformin against doxorubicin-induced cardiotoxicity by identifying FHC and NF
      kappaB as the major mediators of this beneficial effect.

PMID- 23000261
TI  - Cranial nerve involvement as presenting sign of multifocal motor neuropathy.
AB  - Multifocal motor neuropathy (MMN) is characterized by slowly progressive,
      predominantly distal, asymmetric limb weakness and partial conduction blocks (CB)
      of motor axons. Cranial nerve involvement and respiratory failure are uncommon.
      We report two patients who exhibited unilateral hypoglossal and abducens palsy as
      presenting signs. Other remarkable features were autonomic instability and
      respiratory failure due to bilateral phrenic nerve involvement. Treatment with
      intravenous (IV) immunoglobulin (Ig) resulted in an improvement. Patient 2, who
      showed IgM reactivity against ganglioside GM1, has been receiving maintenance
      therapy with IVIg for 7 years. We speculate that cranial weakness of our patients
      could be due to CB similar to those detected in the motor nerves of the
      extremities.

PMID- 23000262
TI  - Ratio of positron emission tomography uptake to tumor size in surgically resected
      non-small cell lung cancer.
AB  - BACKGROUND: In patients with non-small cell lung cancer (NSCLC), previous studies
      have shown a prognostic benefit of maximum standardized uptake (SUV(max)) values
      on positron emission tomography (PET). Because tumor size is also prognostic and
      is associated with SUV(max), we sought to better characterize their relationship.
      We hypothesize that the ratio of SUV(max) to tumor size is a clinically useful
      measurement. METHODS: A retrospective review was performed for patients (tumors
      >= 1 cm) undergoing resection of NSCLC. Patients were placed into quartiles
      (SUV(max) and SUV(max) to tumor size ratio) and compared for clinical and
      pathologic factors. Predictors of SUV(max) and SUV(max) to tumor size ratio on
      survival were evaluated. RESULTS: Among 530 patients, increasing tumor size (odds
      ratio [OR], 2.04; confidence interval [CI], 1.68-2.47; p < 0.001) was an
      independent predictor of higher SUV(max). Patients in quartiles by the ratio of
      SUV(max) to tumor size demonstrated no significant difference in median tumor
      size. Those patients with the highest ratios (QR4, 3.21-27.5) more frequently had
      poorly differentiated tumors (51%; p < 0.001), were likely to have lymph node
      metastases (30%; p < 0.001), and had poor 3-year disease-free survival (DFS)
      (58%; p = 0.013). On multivariate analysis, as a continuous variable SUV(max) to
      tumor size ratio was a stronger independent predictor of survival than SUV(max)
      alone (hazard ratio [HR], 1.06; CI, 1.00-1.13 versus HR, 1.02; CI, 0.99-1.06).
      Using cutpoint analysis, a high SUV(max) to tumor size ratio was also a stronger
      predictor of survival than was high SUV(max) alone, particularly for tumors 1-3
      cm (HR, 1.53; CI, 0.93-2.53 versus HR, 1.15; CI, 0.69-1.93). CONCLUSIONS: The
      ratio of SUV(max) to tumor size may be a more important indicator of prognosis
      than SUV(max) alone in patients with NSCLC. In particular, the use of the ratio
      may be appropriate for identifying patients with small tumors who are at high
      risk for lymph node metastases and poor survival.

PMID- 23000263
TI  - Surgical treatment of nonmalignant tracheoesophageal fistula: a thirty-five year
      experience.
AB  - BACKGROUND: Acquired nonmalignant tracheoesophageal fistula in the adult patient
      develops in a variety of conditions. We have applied surgical closure with
      success for 35 years. METHODS: From 1975 to 1991, 38 patients underwent surgical
      repair of a tracheoesophageal fistula. A retrospective study of 36 additional
      patients undergoing surgical repair from 1992 to 2010 was conducted. RESULTS: The
      most common causes were postintubation injury (n=17, 47%), trauma (n=6, 17%),
      prior laryngectomy (n=6, 17%), and prior esophagectomy (n=4, 11%). Four patients
      presented after failing fistula control with an endoluminal stent. The tracheal
      defect was closed with resection and reconstruction (n=17, 41%), laryngotracheal
      resection (n=5, 12%), membranous tracheal repair (n=17, 41%), or repair over a
      tracheal T tube (n=2, 5%), while esophageal repair consisted of 2-layer closure
      (n=31, 78%), 1-layer closure (n=6, 15%), esophagostomy (n=1, 3%), end-to-end
      esophageal anastomosis (n=1, 3%), or full thickness skin graft reconstruction
      (n=1, 3%). The esophageal and tracheal repairs were buttressed by interposing
      pedicled muscle or omental flaps in all patients. There was 1 postoperative death
      (3%). Recurrence after repair developed only in fistulas arising after
      esophagectomy or laryngectomy (n=4, 11%). Fistula closure was ultimately
      successful in 34 patients (94%). Twenty-nine patients (83%) resumed oral intake
      and 25 patients (71%) were breathing without a tracheal appliance. CONCLUSIONS:
      Successful closure of benign tracheoesophageal fistula is achieved with several
      surgical techniques based on buttressed repair and restoration of normal
      breathing and swallowing. Closure of complex postsurgical fistula may fail.
      Endoluminal stenting was not found useful.

PMID- 23000264
TI  - Splenic morphological changes are accompanied by altered baseline immunity in a
      mouse model of sickle-cell disease.
AB  - Although functional asplenia from infarctions may be a major contributor to
      increased infectious mortality in sickle-cell disease (SCD), this relationship
      has not been fully defined. We used the transgenic Berkeley SCD mouse to define
      blood and splenic immunophenotypic differences in this model compared with
      C57BL/6 and hemizygous controls. In the serum of SCD mice, we found increased
      IgG2a and suppressed IgM, IgG2b, and IgA levels. Serum IL-6 levels in SCD mice
      were elevated, whereas IL-1alpha, CXCL10, and CCL5 levels were decreased. The
      blood of SCD mice had higher white blood cell counts, with an increased
      percentage of lymphocytes and decreases in other leukocytes. Immunophenotyping of
      lymphocytes revealed higher percentages of CD8(+) and T-regulatory cells and
      lower percentages of B cells. SCD mouse spleens exhibited histological
      disorganization, with reduction of defined lymphoid follicles and expansion of
      red pulp, a greater than fourfold increase in splenic mononuclear cells, marked
      expansion of the nucleated red blood cell fraction, and B-cell and CD8(+) T-cell
      lymphopenia. Within the splenic B-cell population, there was a significant
      decrease in B-1a B cells, with a corresponding decrease in IgA secreting plasma
      cells in the gut. Confocal microscopy of spleens demonstrated complete disruption
      of the normal lymphofollicular structure in the white pulp of SCD mice without
      distinct B, T, and marginal zones. Our findings suggest that altered SCD splenic
      morphological characteristics result in an impaired systemic immune response.

PMID- 23000265
TI  - Suppression of scavenger receptors transcription by parasitoid factors.
AB  - Scavenger receptors (SR) are a group of membrane proteins that play central roles
      in various functions, such as immune responses in insects. Members of different
      SR classes were identified from Plutella xylostella larval transcriptome. SR B1
      and B3 were found to be differentially expressed in larvae and pupae. Expression
      of P. xylostella SR genes was significantly altered during immune challenge
      induced in P. xylostella cells (Px) and parasitized larvae. Maternal factors
      injected into the larvae by the endoparasitoid wasp Diadegma semiclausum at
      oviposition include venom and ichnovirus (DsIV) genes to suppress the host immune
      system. Transient expression of two DsIV genes, Vankyrin1 and Repeat element 4
      (Rep4), in Px cells led to significant down-regulation of both SR B1 and B3
      transcript levels, while DsIV Rep4 expression did not change the relative
      transcription levels of SR B3. In conclusion, it appears that the two members of
      the SR family play important roles in innate immune responses in P. xylostella
      and that each member of this group may play different roles in the host
      parasitoid interaction.

PMID- 23000266
TI  - Cathepsins in the kidney of olive flounder, Paralichthys olivaceus, and their
      responses to bacterial infection.
AB  - Cathepsin activities are responsible for mediating various pathways involved in
      immune response, including the apoptosis pathway, toll-like receptor (TLR)
      signaling, cytokine induction and activation of granule serine proteases. In the
      present study, we investigated cathepsin responses in the kidneys of olive
      flounder infected with Streptococcus parauberis, analyzing cathepsin expression
      using a label-free, quantitative proteomic approach in conjunction with
      quantitative real-time polymerase chain reaction (qRT-PCR). In proteomic
      analyses, we detected cathepsin B, D, L and S proteins, noting significant
      decreases and increases in cathepsins B and L, respectively, with infection.
      Taken together with an evaluation of cathepsin B, D, F, K, L, S and X gene
      expression in normal and infected kidneys by qRT-PCR, our results indicate that
      cathepsins B, D, L and S are the dominant lysosomal proteases in the immune
      system of the teleostei, olive flounder. Cathepsins F, K and X were regarded as
      minor cathepsins.

PMID- 23000267
TI  - Effect of the anti-lipopolysaccharide factor isoform 3 (ALFPm3) from Penaeus
      monodon on Vibrio harveyi cells.
AB  - The anti-lipopolysaccharide factor isoform 3 from Penaeus monodon (ALFPm3) has
      previously been shown to have very active in vitro antimicrobial activity against
      a broad range of Gram-positive and Gram-negative bacteria, certain fungi and
      viruses, including known pathogens of P. monodon shrimp. With respect to the
      strong bactericidal effect on Gram-negative and Gram-positive bacteria, the
      ALFPm3 binds to their principal cell wall components, lipopolysaccharide (LPS)
      and lipoteichoic acid (LTA), with a high affinity. The aim of this study was,
      therefore, to reveal the effects of treating ALFPm3 on membrane of Vibrio
      harveyi, a P. monodon pathogenic Gram-negative bacterium. The recombinant
      (r)ALFPm3 protein was found to localize on the V. harveyi cells in vivo, followed
      by inducing membrane permeabilization and leakage of cytoplasmic components.
      Moreover, the effect of rALFPm3 treatment on the bacterial cell morphology was
      confirmed by scanning and transmission electron microscopy. Membrane disruption
      and damage, bleb and pore formation, and the leakage of cytoplasmic contents were
      all clearly observed. Taken together, these results suggested that ALFPm3
      effectively kills bacteria through bacterial membrane permeabilization.

PMID- 23000268
TI  - Characterization and gene expression analysis of the two main Th17 cytokines (IL
      17A/F and IL-22) in turbot, Scophthalmus maximus.
AB  - This report describes the cloning, characterization and gene expression pattern
      of two Th17 cytokines, interleukin (IL)-17A/F and -22, in turbot Scophthalmus
      maximus. The turbot IL-17A/F cDNA contains a 516 bp open reading frame encoding a
      deduced IL-17A/F protein of 171 amino acid (aa) residues, containing a predicted
      signal peptide of 31 aa. Turbot IL-22 had a 564 bp ORF coding for a 187 aa
      protein with a 33 aa signal peptide. The turbot IL-22 protein contained a typical
      IL-10 family signature. Both cytokines had highest expression levels in the
      intestine followed by head kidney and gills. Stimulation with the Gram negative
      bacterium Aeromonas salmonicida was able to modulate IL-17A/F and IL-22
      expression in head kidney, spleen and liver but not the intestine. PMA and PHA
      were also able to induce the expression of both cytokines, suggesting that, as
      expected, T-cells are likely the main producers of these molecules in turbot as
      in mammals.

PMID- 23000269
TI  - MRI-assessed regional pulse wave velocity for predicting absence of regional
      aorta luminal growth in marfan syndrome.
AB  - BACKGROUND: In patients with Marfan syndrome (MFS), increased aortic wall
      stiffening may lead to progressive aortic dilatation. Aortic Pulse Wave Velocity
      (PWV), a marker of wall stiffness can be assessed regionally, using in-plane
      multi-directional velocity-encoded MRI. This study examined the diagnostic
      accuracy of regional PWV for prediction of regional aortic luminal growth during
      2-year follow-up in MFS patients. METHODS: In twenty-one MFS patients (mean age
      36 +/- 15 years, 11 male) regional PWV and aortic luminal areas were assessed by
      1.5 T MRI. At 2-year follow-up, the incidence of luminal growth, defined as mean
      luminal diameter increase >2mm was determined for five aortic segments (S1,
      ascending aorta; S2, aortic arch; S3, thoracic descending aorta, S4, supra-renal
      and S5, infra-renal abdominal aorta). Regional PWV at baseline was considered
      increased when exceeding age-related normal PWV (healthy volunteers (n=26; mean
      age 30 +/- 10 years, 15 male)) by two standard-errors. Sensitivity and
      specificity of regional PWV-testing for prediction of regional luminal growth
      were determined. RESULTS: Regional PWV at baseline was increased in 17 out of 102
      segments (17%). Significant luminal growth at follow-up was reported in 14
      segments (14%). The specificity of regional PWV-testing was >= 78% for all aortic
      segments, sensitivity was <= 33%. CONCLUSIONS: Regional PWV was significantly
      increased in MFS patients as compared to healthy volunteers within similar age
      range, in all aortic segments except the ascending aorta. Furthermore, regional
      PWV-assessment has moderate to high specificity for predicting absence of
      regional aortic luminal growth for all aortic segments in MFS patients.

PMID- 23000271
TI  - Use of postmortem computed tomography to reveal acute subdural hematoma in a
      severely decomposed body with advanced skeletonization.
AB  - An 81-year-old man was found dead 1 month after he had disappeared following a
      visit to a hot spring resort in early autumn. The body showed severe postmortem
      changes with advanced skeletonization from the head to the abdomen as well as
      putrefactive and autolytic changes in the remaining tissues. The thoracic and
      abdominal organs had been lost. Naked eye examination revealed soft tissue
      injuries accompanied by ragged edges and characteristic punctures with no signs
      of vitality, suggesting that these injuries had been due to postmortem animal
      scavenging. However, bruises were prominent on the anterior parts of both lower
      extremities. Postmortem computed tomography (PMCT) scan demonstrated subdural
      hematoma over the right cerebral hemisphere, although the brain itself had
      undergone putrefactive and autolytic changes. Subsequent autopsy confirmed the
      presence of a 140 g acute subdural hematoma, which would likely have been fatal.
      This case illustrates that PMCT is able to yield important information about
      possible cause of death, even in a partially skeletonized body.

PMID- 23000270
TI  - Reprogramming of DNA methylation in pollen guides epigenetic inheritance via
      small RNA.
AB  - Epigenetic inheritance is more widespread in plants than in mammals, in part
      because mammals erase epigenetic information by germline reprogramming. We
      sequenced the methylome of three haploid cell types from developing pollen: the
      sperm cell, the vegetative cell, and their precursor, the postmeiotic microspore,
      and found that unlike in mammals the plant germline retains CG and CHG DNA
      methylation. However, CHH methylation is lost from retrotransposons in
      microspores and sperm cells and restored by de novo DNA methyltransferase guided
      by 24 nt small interfering RNA, both in the vegetative nucleus and in the embryo
      after fertilization. In the vegetative nucleus, CG methylation is lost from
      targets of DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), and their homologs,
      which include imprinted loci and recurrent epialleles that accumulate
      corresponding small RNA and are premethylated in sperm. Thus genome reprogramming
      in pollen contributes to epigenetic inheritance, transposon silencing, and
      imprinting, guided by small RNA.

PMID- 23000272
TI  - Multi-level visual adaptation: dissociating curvature and facial-expression
      aftereffects produced by the same adapting stimuli.
AB  - Adaptation aftereffects offer a critical window onto sensory processing in the
      brain. However, such sensory processing is hierarchical, progressing from the
      extraction of simple features to the representation of complex patterns. The way
      that adaptation depends on coordinated changes across different levels of the
      hierarchy has been studied. However, when a given adapting stimulus produces both
      a low- and a high-level aftereffect, it remains unclear whether the high-level
      aftereffect is a passive reflection of low-level adaptation, or whether it is
      generated, at least partially, de novo in high-level areas. We assembled the two
      key ingredients needed for investigating this question psychophysically. One
      ingredient involves perceptual tasks that depend rather exclusively on low or
      high levels of processing, and yet involve partially identical stimuli that
      inspire cross-level adaptation. For this, we considered the discrimination of
      curvature or facial expression using curves or cartoon faces. The other
      ingredient is spatial or temporal stimulus manipulations that limit adaptation to
      either low or high levels. For this, we used crowding and brief presentations. We
      found that crowding an adapting curve with flanking curves reduces the curvature
      aftereffect much more than the facial-expression aftereffect, and vice versa for
      crowding the adapting face with flanking faces. Additionally, reducing adaptation
      time to a cartoon face diminishes the curvature aftereffect more drastically than
      the facial-expression aftereffect. These results suggest that high-level
      aftereffects, even when generated by a low-level adaptor, are not completely
      inherited from lower levels, and offer a window into the determining factors.

PMID- 23000273
TI  - Standardized F1: a consistent measure of strength of modulation of visual
      responses to sine-wave drifting gratings.
AB  - The magnitude of spike-responses of neurons in the mammalian visual system to
      sine-wave luminance-contrast-modulated drifting gratings is modulated by the
      temporal frequency of the stimulation. However, there are serious problems with
      consistency and reliability of the traditionally used methods of assessment of
      strength of such modulation. Here we propose an intuitive and simple tool for
      assessment of the strength of modulations in the form of standardized F1 index,
      zF1. We define zF1 as the ratio of the difference between the F1 (component of
      amplitude spectrum of the spike-response at temporal frequency of stimulation)
      and the mean value of spectrum amplitudes to standard deviation along all
      frequencies in the spectrum. In order to assess the validity of this measure, we
      have: (1) examined behavior of zF1 using spike-responses to optimized drifting
      gratings of single neurons recorded from four 'visual' structures (area V1 of
      primary visual cortex, superior colliculus, suprageniculate nucleus and caudate
      nucleus) in the brain of commonly used visual mammal - domestic cat; (2) compared
      the behavior of zF1 with that of classical statistics commonly employed in the
      analysis of steady-state responses; (3) tested the zF1 index on simulated spike
      trains generated with threshold-linear model. Our analyses indicate that zF1 is
      resistant to distortions due to the low spike count in responses and therefore
      can be particularly useful in the case of recordings from neurons with low firing
      rates and/or low net mean responses. While most V1 and a half of caudate neurons
      exhibit high zF1 indices, the majorities of collicular and suprageniculate
      neurons exhibit low zF1 indices. We conclude that despite the general
      shortcomings of measuring strength of modulation inherent in the linear system
      approach, zF1 can serve as a sensitive and easy to interpret tool for detection
      of modulation and assessment of its strength in responses of visual neurons.

PMID- 23000274
TI  - Fundus autofluorescence and optical coherence tomography in relation to visual
      function in Usher syndrome type 1 and 2.
AB  - Purpose of this study was to characterize retinal disease in Usher syndrome using
      fundus autofluorescence and optical coherence tomography. Study included 54
      patients (26 male, 28 female) aged 7-70 years. There were 18 (33%) USH1 and 36
      (67%) USH2 patients. 49/52 (94%) patients were found to carry at least one
      mutation in Usher genes. Ophthalmological examination included assessment of
      Snellen visual acuity, color vision with Ishihara tables, Goldmann visual fields
      (targets II/1-4 and V/4), microperimetry, fundus autofluorescence imaging and
      optical coherence tomography. Average age at disease onset (nyctalopia) was
      significantly lower in USH1 than USH2 patients (average 9 vs. 17 years,
      respectively; p<0.01); however no significant differences were found regarding
      type of autofluorescence patterns, frequency of foveal lesions and CME, rate of
      disease progression and age at legal blindness. All representative eyes had
      abnormal fundus autofluorescence of either hyperautofluorescent ring (55%),
      hyperautofluorescent foveal patch (35%) or foveal atrophy (10%). Disease duration
      of more than 30 years was associated with a high incidence of abnormal central
      fundus autofluorescence (patch or atrophy) and visual acuity loss.

PMID- 23000275
TI  - An improved method of transcutaneous cisterna magna puncture for cerebrospinal
      fluid sampling in rats.
AB  - A simple, reproducible and chronic technique of cerebrospinal fluid (CSF)
      collection in rats was developed by direct cisterna magna (CM) puncture utilizing
      stereotaxic apparatus. CSF collection apparatus was constructed using 1 mL
      syringe, silicone tubing, 21G disposable needle and water. Animal was placed on
      an elevated platform over stereotaxic apparatus base and puncture site was
      identified with the aid of stereotaxic co-ordinates. The volume of CSF collected
      varied from 100 to 180 MUL with mean CSF volume of 150 MUL. Neurological deficits
      were recorded according to the modified Bederson's scoring system 24h post CSF
      collection and differential cell count in CSF samples was performed. Animals
      continued to be normal with regular feed intake and gained body weight (~24%)
      even after repeated sampling for four weeks and showed no severe neurological
      deficits (mean Bederson score<1 for four weeks). Neuropharmacokinetic data for
      Phenytoin sodium, MS 275 and Valproic acid (VPA) demonstrated CSF uptake with
      CSF(AUC)/plasma(AUC) ratio (K(p,CSF)) of 0.09, 0.01 and 0.33, respectively. This
      model exemplifies the 3R's of animal use and has been successfully implemented at
      Orchid Chemicals and Pharmaceuticals Limited for lead optimization of CNS
      penetrating HDAC inhibitors.

PMID- 23000276
TI  - Integrating sensory evaluation in adaptive conjoint analysis to elaborate the
      conflicting influence of intrinsic and extrinsic attributes on food choice.
AB  - Sensory properties and packaging information are factors which considerably
      contribute to food choice. We present a new methodology in which sensory
      preference testing was integrated in adaptive conjoint analysis. By simultaneous
      variation of intrinsic and extrinsic attributes on identical levels, this
      procedure allows assessing the importance of attribute/level combinations on
      product selection. In a set-up with nine pair-wise comparisons and four
      subsequent calibration assessments, 101 young consumers evaluated vanilla yoghurt
      which was varied in fat content (four levels), sugar content (two levels) and
      flavour intensity (two levels); the same attribute/level combinations were also
      presented as extrinsic information. The results indicate that the evaluation of a
      particular attribute may largely diverge in intrinsic and in extrinsic
      processing. We noticed from our utility values that, for example, the acceptance
      of yoghurt increases with an increasing level of the actual fat content, whereas
      acceptance diminishes when a high fat content is labelled on the product. This
      article further implicates that neglecting these diverging relationships may lead
      to an over- or underestimation of the importance of an attribute for food choice.

PMID- 23000277
TI  - The associations between TV viewing, food intake, and BMI. A prospective analysis
      of data from the Longitudinal Study of Australian Children.
AB  - OBJECTIVE: Despite cross-sectional evidence of a link between TV viewing and BMI
      in early childhood, there has been limited longitudinal exploration of this
      relationship. The aim of the present study was to explore the potential bi
      directionality of the relationship between TV viewing and child BMI. A secondary
      aim was to evaluate whether this relationship is mediated by dietary intake.
      STUDY DESIGN: Parents of 9064 children (4724 recruited at birth, 4340 recruited
      at age 4) from the Longitudinal Study of Australian Children (LSAC) completed
      measures of their child's dietary intake and TV viewing habits at three
      equidistant time points, separated by 2years. Objective measures of height and
      weight were also obtained at each time point to calculate BMI. Cross-lagged panel
      analyses were conducted to evaluate potential bi-directional associations between
      TV viewing and child BMI, and to evaluate mediation effects of dietary intake for
      this relationship. RESULTS: Our longitudinal findings suggest that the
      relationship between TV viewing and BMI is bi-directional: Individuals who watch
      TV are more likely to gain weight, and individuals who are heavier are also more
      likely to watch TV. Interestingly, dietary intake mediated the BMI-TV viewing
      relationship for the older children, but not for the birth cohort. CONCLUSIONS:
      Present findings suggest that sedentary behaviours, particularly when coupled
      with unhealthy dietary habits, constitute a significant risk factor for excessive
      weight gain in early childhood. Interventions targeted at helping parents to
      develop healthy TV viewing and eating habits in their young children are clearly
      warranted.

PMID- 23000278
TI  - Investigation of anthropometric, biochemical and dietary parameters of obese
      children with and without non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) in children has been recognized as a
      major health burden. The high prevalence of NAFLD is probably due to the
      contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary
      lifestyle. The purpose of this study was to investigate anthropometric,
      biochemical and dietary intake parameters of obese Greek children with and
      without NAFLD. Eighty two obese children aged 8-15 (45 boys/37 girls)
      participated in the study. Ultrasonography (US) was used to diagnose NAFLD in all
      participated subjects. Liver indexes were measured in all children. A 3-day
      dietary was recorded for all subjects. Data for continuous variables is expressed
      as mean values+/-standard deviation. Thirty-five out of eighty two subjects
      (42.6%) had NAFLD. Body Mass Index levels (P<0.001) and Waist Circumference
      (P<0.046) levels were statistically higher in the children with severe NAFLD
      (37.2kg/m(2)+/-6.2 and 102.9cm+/-14) compared to children with mild NAFLD
      (26.6kg/m(2)+/-3.3 and 86.1cm+/-9.9) and absent of fatty liver (25.3kg/m(2)+/-3.6
      and 85.2cm+/-11.2), respectively. Total carbohydrates intakes were significantly
      higher in subjects with NAFLD (288.8g+/-70.6) compared to children without NAFLD
      (244.5g+/-67.5), (P<0.001). Saturated fatty acids (SFAs) intake was
      proportionally increased to the degree of hepatic steatosis, while n-3 fatty
      acids (n-3 FA) consumption was inversely related with NAFLD. In multiple
      regression analysis of factors associated with NAFLD, HOMA-IR (OR: 1.260, 95%CI:
      1.110-1.470, P<0.001) and n-3FA (OR:1.921, 95%CI:1.132-2.187, P<0.001) were the
      most significant ones. Our results showed that IR, high dietary intakes of CHO
      and SFA and a low dietary consumption of fiber and n-3 FA were positively
      associated with the pathogenesis of NAFLD.

PMID- 23000279
TI  - Reducing suffering in animal models and procedures involving seizures,
      convulsions and epilepsy.
AB  - This report is based on discussions and submissions from an expert working group
      consisting of veterinarians, animal care staff and scientists with expert
      knowledge relevant to the field and aims to facilitate the implementation of the
      Three Rs (replacement, reduction and refinement) in the use of animal models or
      procedures involving seizures, convulsions and epilepsy. Each of these conditions
      will be considered, the specific welfare issues discussed, and practical measures
      to reduce animal use and suffering suggested. The emphasis is on refinement since
      this has the greatest potential for immediate implementation, and some general
      issues for refinement are summarised to help achieve this, with more detail
      provided on a range of specific refinements.

PMID- 23000280
TI  - Characterization of a refinement of the "pylorus ligation" model of rat gastric
      ulceration resulting in "no pain" and a more specific pharmacological response.
AB  - INTRODUCTION: The pharmacological assessment of the factors for gastric
      protection of a test substance should involve experimental models that can
      determine the involvement of cytoprotective factors, as well as their influence
      on the secretion of hydrochloric acid. The original protocol of pylorus ligation
      in rats proposed by Shay et al. in 1945, still in use today, provides a latency
      time of 240 min without considering the effect of postoperative pain in the
      mechanisms of peptic ulcer. This paper proposes a modification of this
      experimental protocol by eliminating the pain throughout the postoperative
      period, as a refinement of the test with consequent improvement of the
      pharmacological response. METHODS: Adult male Wistar/Uni rats underwent surgical
      ligation of the pylorus and were kept anesthetized throughout the experimental
      period (4h) in contrast to the other experimental groups that followed the
      original protocol proposed by Shay et al., 1945. RESULTS: We were able to
      determine effective doses for a positive control, as well as of a variety of
      secretagogues in the new experimental protocol proposed. DISCUSSION: The
      suppression of post-surgical pain, through the use of anesthesia throughout the
      experimental period, brought several benefits for the study of gastric acid
      secretion, rendering a more homogeneous pharmacologic response in non-inbred
      animals, thus being an effective experimental procedure.

PMID- 23000281
TI  - Osteoporosis risk and bone mineral density levels in patients with Parkinson's
      disease: a meta-analysis.
AB  - INTRODUCTION: Parkinson's disease (PD) and osteoporosis are common diseases which
      affect a substantial portion of the elderly population. Accumulating evidence
      supports that PD patients have a high risk for osteoporosis in recent years. The
      purpose of the present study is to perform a meta-analysis on the risk of
      osteoporosis and bone mineral density (BMD) levels in PD patients. METHODS: We
      searched all articles indexed in Medline, SciVerse Scopus and Cochrane Library
      published up to January 2012 concerning the association between PD and risk of
      osteoporosis or BMD levels. In total, 15 studies were included in the meta
      analysis. RESULTS: The results indicated that PD patients are at higher risk for
      osteoporosis (summary OR=1.18, 95% CI=[1.09, 1.27]) than healthy controls. The
      gender subgroup analysis suggested that PD male patients have a higher risk for
      osteoporosis than female patients (female patients: summary OR=1.16, 95%
      CI=[1.07, 1.26]; male patients: summary OR=2.44, 95% CI=[1.37, 4.34]). Further
      meta-analysis showed that PD patients have a lower hip, lumbar spine and femoral
      neck BMD than healthy controls. The gender subgroup analysis found a lower BMD in
      PD female patients than controls, while no obvious difference was observed in PD
      male patients and controls. CONCLUSIONS: This meta-analysis suggested that PD
      patients are at higher risk for osteoporosis and have lower BMD levels than
      healthy controls overall.

PMID- 23000282
TI  - Fused mesoionic heterocyclic compounds are a new class of aryl hydrocarbon
      receptor (AhR) agonist of exceptional potency.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent ligands of
      the aryl hydrocarbon receptor (AhR). Here, we show that a novel fused mesoionic
      heterocyclic compound (AZ1) is ~5-fold more potent than TCDD in both rat and
      human cell lines at inducing cytochrome P4501A1 RNA. In rat H4IIE cells, AZ1 gave
      an EC(50)=5.05 pM (95% CI=2.81-9.09 pM) whereas TCDD had an EC(50)=25.5 pM (95%
      CI=18.2-36.0 pM). AZ1 was also more potent than TCDD (5-10-fold) at inducing the
      AhR-related CYP1A2 and CYP1B1 genes, showing that AZ1 is more potent at inducing
      multiple genes. In human MCF-7 cells AZ1 gave an EC(50)=65.4 pM (95% CI=45.6-93.7
      pM) and TCDD an EC(50)=241 pM (95% CI=161-362 pM), showing that AZ1 was more
      potent than TCDD at inducing CYP1A1 RNA in multiple species. Finally, the
      compound bound to rat cytosolic AhR with 6-fold higher affinity than TCDD,
      showing that the highly potent agonism of this substance is mediated via a high
      affinity for the receptor. This data shows that this novel compound, which shares
      structural similarities with various naphthoflavones, is a potent ligand of the
      AhR.

PMID- 23000283
TI  - Ethoxylated adjuvants of glyphosate-based herbicides are active principles of
      human cell toxicity.
AB  - Pesticides are always used in formulations as mixtures of an active principle
      with adjuvants. Glyphosate, the active ingredient of the major pesticide in the
      world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants
      are generally considered as inert diluents. Since side effects for all these
      compounds have been claimed, we studied potential active principles for toxicity
      on human cells for 9 glyphosate-based formulations. For this we detailed their
      compositions and toxicities, and as controls we used a major adjuvant (the
      polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation
      without glyphosate. This was performed after 24h exposures on hepatic (HepG2),
      embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial
      activities, membrane degradations, and caspases 3/7 activities. The compositions
      in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all
      formulations are more toxic than glyphosate, and we separated experimentally
      three groups of formulations differentially toxic according to their
      concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be
      the most toxic principle against human cells, even if others are not excluded. It
      begins to be active with negative dose-dependent effects on cellular respiration
      and membrane integrity between 1 and 3ppm, at environmental/occupational doses.
      We demonstrate in addition that POE-15 induces necrosis when its first
      micellization process occurs, by contrast to glyphosate which is known to promote
      endocrine disrupting effects after entering cells. Altogether, these results
      challenge the establishment of guidance values such as the acceptable daily
      intake of glyphosate, when these are mostly based on a long term in vivo test of
      glyphosate alone. Since pesticides are always used with adjuvants that could
      change their toxicity, the necessity to assess their whole formulations as
      mixtures becomes obvious. This challenges the concept of active principle of
      pesticides for non-target species. 

PMID- 23000285
TI  - Association of glutathione S-transferase M1 polymorphisms and lung cancer risk in
      a Chinese population.
AB  - BACKGROUND: Genetic polymorphisms of glutathione S-transferase M1 (GSTM1) are
      thought to have significant effects on the metabolism of environmental
      carcinogens and thus on lung cancer risk, but the reported results are not always
      consistent. The aim of this study is to investigate the relationship between
      GSTM1 genetic polymorphism and lung cancer risk in a Chinese population. METHODS:
      A population-based control study was conducted in 360 lung cancer patients and
      360 cancer-free controls. The genotype of the GSTM1 gene was determined by using
      a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay. RESULTS: We observed a stronger association between GSTM1 null genotype
      and lung cancer [odds ratio (OR)=1.59, 95% confidence interval (CI)=1.17, 2.17;
      P=0.003]. This association was also found in squamous cell carcinoma (OR=1.73,
      95% CI=1.16, 2.59; P=0.008). In the analysis combining GSTM1 polymorphism and
      smoking, smokers with the null genotype who had smoked for >= 30 pack-years had
      higher risk (OR=10.06, 95% CI=5.16, 19.61; P<0.001) compared with non-smokers
      with the wild-type genotype. CONCLUSIONS: This study suggested that GSTM1
      polymorphism plays a role in the development of lung cancer and modifies the risk
      for smoking-related lung cancer in a Chinese population.

PMID- 23000286
TI  - High prevalence of ESBL-producing Escherichia coli isolates among hemodialysis
      patients in Portugal: appearance of ST410 with the bla(CTX-M-14) gene.
AB  - Ten extended-spectrum beta-lactamase-producing Escherichia coli isolates were
      detected among 121 fecal samples (8.3%) recovered from hemodialysis patients in
      Portugal. The isolates harbored the bla(CTX-M-15), bla(CTX-M-14a), and/or bla(CTX
      M-1) genes. A new sequence type, ST2229, was detected, and this study also
      reports, for the first time, ST410 CTX-M-14-producing isolates.

PMID- 23000284
TI  - Early life stage trimethyltin exposure induces ADP-ribosylation factor expression
      and perturbs the vascular system in zebrafish.
AB  - Trimethyltin chloride (TMT) is an organotin contaminant, widely detected in
      aqueous environments, posing potential human and environmental risks. In this
      study, we utilized the zebrafish model to investigate the impact of transient TMT
      exposure on developmental progression, angiogenesis, and cardiovascular
      development. Embryos were waterborne exposed to a wide TMT concentration range
      from 8 to 96 h post fertilization (hpf). The TMT concentration that led to
      mortality in 50% of the embryos (LC(50)) at 96 hpf was 8.2 MUM; malformations in
      50% of the embryos (EC(50)) was 2.8 MUM. The predominant response observed in
      surviving embryos was pericardial edema. Additionally, using the Tg (fli1a: EGFP)
      y1 transgenic zebrafish line to non-invasively monitor vascular development, TMT
      exposure led to distinct disarrangements in the vascular system. The most
      susceptible developmental stage to TMT exposure was between 48 and 72 hpf. High
      density whole genome microarrays were used to identify the early transcriptional
      changes following TMT exposure from 48 to 60 hpf or 72 hpf. In total, 459
      transcripts were differentially expressed at least 2-fold (P<0.05) by TMT
      compared to control. Using Ingenuity Pathway Analysis (IPA) tools, it was
      revealed that the transcripts misregulated by TMT exposure were clustered in
      numerous categories including metabolic and cardiovascular disease, cellular
      function, cell death, molecular transport, and physiological development. In situ
      localization of highly elevated transcripts revealed intense staining of ADP
      ribosylation factors arf3 and arf5 in the head, trunk, and tail regions. When
      arf5 expression was blocked by morpholinos, the zebrafish did not display the
      prototypical TMT-induced vascular deficits, indicating that the induction of arf5
      was necessary for TMT-induced vascular toxicity.

PMID- 23000287
TI  - High clonality and diversity of virulence determinants among bla(PSE)-positive
      Salmonella Typhimurim isolates recovered in three geographically distant Spanish
      hospitals.
AB  - Molecular typing, the presence of Salmonella genomic island 1 (SGI1), and
      virulence factors were studied in 45 bla(PSE)-positive S. Typhimurium isolates
      from 3 hospitals. All isolates belonged to sequence type ST19, presented low
      clonal diversity, and harbored SGI1. The wide diversity of virulence factors was
      classified into 3 major virulotype groups.

PMID- 23000288
TI  - The relationship of vitamin D status, smoking, and colorectal adenoma: a
      retrospective study in an ethnically diverse community.
AB  - OBJECTIVE: Circulating 25-hydroxyvitamin D (25OHD) level is suggested to be
      negatively correlated with risk of colorectal cancer (CRC) and colorectal adenoma
      (CRA), but most of the epidemiological data were originated amongst Caucasians
      and African Americans. This study aimed to investigate the relationship between
      vitamin D status, smoking and CRA in an ethnically diverse community with a high
      Hispanic density. METHODS: In this retrospective study, we included 233 patients
      who underwent complete colonoscopies from 2009 to 2011, and their serum 25OHD
      levels in the winter season had been measured. Among them, 65 adenoma cases and
      168 adenoma-free controls were identified and evaluated for the association of
      CRA with smoking, ethnicity and serum 25OHD level using unstratified and
      stratified multivariate logistic regression analyses. RESULTS: In our study
      participants, the mean serum 25OHD level and the percentage of Hispanics were
      lower in the adenoma group versus the control group, while no black-white
      difference was noted in the CRA prevalence. When adjusted for 25OHD level, the
      lower rate of adenoma in Hispanics compared to non-Hispanics was attenuated and
      became statistically insignificant. A mild protective effect of vitamin D (6%
      reduction) on the CRA risk was found significant for active smokers, but not for
      non-smokers. A detrimental impact of smoking in the CRA risk was only shown among
      non-Hispanic patients, but not among Hispanics irrespective of vitamin D status.
      CONCLUSIONS: Our data suggest a marked distinction between Hispanics and non
      Hispanics in the risk of CRA. The reduced adenoma prevalence among Hispanics vs.
      non-Hispanics could be partially explained by vitamin D status, cigarette smoking
      and their interactions. Future larger-sized multi-center studies on vitamin D
      status and ethnicity, as well as dietary, behavioral, genetic factors and their
      interactions for CRA and CRC are needed. This article is part of a Special Issue
      entitled 'Vitamin D Workshop'.

PMID- 23000290
TI  - The effects of windrow composting on the viability of Parascaris equorum eggs.
AB  - Parascaris equorum generally infects horses less than 18 months old and its
      pathological effects can be severe. Infection occurs when larvated eggs, present
      in pastures, paddocks, stalls, and on feeding and watering equipment are
      ingested. The purpose of this study was to examine the effects of windrow
      composting on the viability of P. equorum eggs at a cooperating central Kentucky
      horse farm. Three grams of feces containing 2216 P. equorum eggs per gram were
      sealed in filter bag sentinel chambers. Chambers were exposed to 1 of 3
      treatments: constant exposure or intermittent exposure to the interior of the
      windrow; controls were stored at 4 degrees C. At day 0, all chambers in the
      experimental treatments were placed in the center of 10 locations of the windrow.
      On subsequent days when the windrow was turned, chambers in the constant exposure
      treatment were returned to the interior of the windrow and chambers in the
      intermittent exposure treatment were alternated between resting on top of, or
      inside, the windrow. Chambers from each treatment and control chambers were
      removed at days 2, 4, 6, 8, 10, 12, 14, and 18; and incubated for 21 days at room
      temperature (24 degrees C). After incubation, eggs were recovered from the
      chambers using double centrifugation flotation. Eggs were evaluated
      microscopically, staged according to development and classified as viable or
      nonviable based on whether embryonation to the larval stage had occurred. Results
      were reported as the mean percent viable eggs for each treatment and time point.
      A mixed linear model with repeated measures was used to evaluate the influence of
      experimental day and treatment on the percent viability of P. equorum eggs.
      Chambers treated with constant exposure contained 10.73% (SD=0.29) viable eggs on
      day 2 and declined to an average of 0.00% by day 8. Chambers exposed to the
      intermittent treatment contained 16.08% (SD=0.26) viable eggs on day 2 and
      decreased to 0.00% by day 6. Control chambers for days 2, 4, 6, 8, 10, 12, 14,
      and 18 all had viabilities above 79.00%. A significant fixed effect of
      experimental day (p<0.0001) and compost treatment (p<0.0001) was observed. There
      was no significant interaction between experimental day and compost treatment
      (p>0.7459). The results of this study demonstrate that windrow composting was
      effective at rendering P. equorum eggs nonviable when it was tested under the
      conditions at a working horse farm.

PMID- 23000289
TI  - Prenatal cigarette smoking: Long-term effects on young adult behavior problems
      and smoking behavior.
AB  - We examined the long-term effects of prenatal cigarette smoke exposure (PCSE) on
      the behavior problems and smoking behavior of 22-year-old offspring. The mothers
      of these offspring were interviewed about their tobacco and other drug use during
      pregnancy at the fourth and seventh gestational months, and at delivery. Data on
      the offspring are from interviews at age 22 (n=608). Behavior problems were
      measured by the Adult Self-Report (ASR) with the following outcome scales: total
      behavior problems, externalizing, internalizing, attention, anxiety/depression,
      withdrawn, thought, intrusive, aggression, somatic and rule breaking behavioral
      problems. Young adult smoking behavior was measured using self-reported average
      daily cigarettes, and was validated with urine cotinine. Nicotine dependence was
      measured with the Fagerstrom Tobacco and Nicotine Dependence (FTND) scale.
      Regression analyses tested the relations between trimester-specific PCSE and
      young adult's behavioral problems and smoking behavior, adjusting for demographic
      and maternal psychological characteristics, and other prenatal substance
      exposures. Exposed young adults had significantly higher scores on the
      externalizing, internalizing, aggression, and somatic scales of the ASR. These
      young adults were also more likely to have a history of arrests. Young adults
      with PCSE also had a higher rate of smoking and nicotine dependence. Our previous
      findings of the relations between PCSE and aggressive behavior in early childhood
      and PCSE and smoking behavior in early adolescence extend into young adulthood.

PMID- 23000291
TI  - Countdown to 2015: changes in official development assistance to maternal,
      newborn, and child health in 2009-10, and assessment of progress since 2003.
AB  - BACKGROUND: Tracking of financial resources to maternal, newborn, and child
      health provides crucial information to assess accountability of donors. We
      analysed official development assistance (ODA) flows to maternal, newborn, and
      child health for 2009 and 2010, and assessed progress since our monitoring began
      in 2003. METHODS: We coded and analysed all 2009 and 2010 aid activities from the
      database of the Organisation for Economic Co-operation and Development, according
      to a functional classification of activities and whether all or a proportion of
      the value of the disbursement contributed towards maternal, newborn, and child
      health. We analysed trends since 2003, and reported two indicators for monitoring
      donor disbursements: ODA to child health per child and ODA to maternal and
      newborn health per livebirth. We analysed the degree to which donors allocated
      ODA to 74 countries with the highest maternal and child mortality rates
      (Countdown priority countries) with time and by type of donor. FINDINGS: Donor
      disbursements to maternal, newborn, and child health activities in all countries
      continued to increase, to $6511 million in 2009, but slightly decreased for the
      first time since our monitoring started, to $6480 million in 2010. ODA for such
      activities to the 74 Countdown priority countries continued to increase in real
      terms, but its rate of increase has been slowing since 2008. We identified strong
      evidence that targeting of ODA to countries with high rates of maternal mortality
      improved from 2005 to 2010. Targeting of ODA to child health also improved but to
      a lesser degree. The share of multilateral funding continued to decrease but,
      relative to bilaterals and global health initiatives, was better targeted.
      INTERPRETATION: The recent slowdown in the rate of funding increases is worrying
      and likely to partly result from the present financial crisis. Tracking of donor
      aid should continue, to encourage donor accountability and to monitor performance
      in targeting aid flows to those in most need. FUNDING: Bill & Melinda Gates
      Foundation; World Bank; Governments of Australia, Canada, Norway, Sweden, and the
      UK.

PMID- 23000292
TI  - Ongoing bleeding in acute intracerebral haemorrhage.

PMID- 23000293
TI  - Synthesis of a potent photoreactive acidic gamma-secretase modulator for target
      identification in cells.
AB  - Supramolecular self-assembly of amyloidogenic peptides is closely associated with
      numerous pathological conditions. For instance, Alzheimer's disease (AD) is
      characterized by abundant amyloid plaques originating from the proteolytic
      cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases.
      Compounds named gamma-secretase modulators (GSMs) can shift the substrate
      cleavage specificity of gamma-secretase toward the production of non
      amyloidogenic, shorter Abeta fragments. Herein, we describe the synthesis of
      highly potent acidic GSMs, equipped with a photoreactive diazirine moiety for
      photoaffinity labeling. The probes labeled the N-terminal fragment of presenilin
      (the catalytic subunit of gamma-secretase), supporting a mode of action involving
      binding to gamma-secretase. This fundamental step toward the elucidation of the
      molecular mechanism governing the GSM-induced shift in gamma-secretase
      proteolytic specificity should pave the way for the development of improved drugs
      against AD.

PMID- 23000295
TI  - Synthesis of Staphylococcus aureus type 5 capsular polysaccharide repeating unit
      using novel L-FucNAc and D-FucNAc synthons and immunochemical evaluation.
AB  - Staphylococcus aureus is a major cause of nosocomial infections. Glycoconjugates
      of type 5 and 8 capsular polysaccharides have been investigated for vaccine
      application. The proposed structure of type 5 polysaccharide is: ->4-beta-D
      ManNAcA-(1->4)-alpha-L-FucNAc(3OAc)-(1->3)-beta-D-FucNAc-(1->. The
      stereocontrolled insertion of these three glycosydic bonds is a real synthetic
      challenge. In the present paper we report the preparation of two novel versatile
      L- and D-fucosamine synthons from commercially available starting materials. In
      addition we applied the two building blocks to the synthesis of type 5
      trisaccharide repeating unit. The immunochemical properties of the synthesized
      trisaccharide were assessed by competitive ELISA and by immunodot blot analysis
      using sera of mice immunized with type 5 polysaccharide conjugated to CRM(197).
      The results suggest that although the type 5 S. aureus trisaccharide is
      recognized by specific anti polysaccharide antibodies in dot blot, structures
      longer than the trisaccharide may be needed in order to significantly compete
      with the native type 5 polymer in the binding with sera from mice immunized with
      S. aureus type 5 polysaccharide-CRM(197) conjugate.

PMID- 23000294
TI  - 1,3-Azoles from ortho-naphthoquinones: synthesis of aryl substituted imidazoles
      and oxazoles and their potent activity against Mycobacterium tuberculosis.
AB  - Twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and
      evaluated against susceptible and rifampicin- and isoniazid-resistant strains of
      Mycobacterium tuberculosis. Among all the compounds evaluated, fourteen presented
      MIC values in the range of 0.78 to 6.25 MUg/mL against susceptible and resistant
      strains of M. tuberculosis. Five structures were solved by X-ray crystallographic
      analysis. These substances are promising antimycobacterial prototypes.

PMID- 23000296
TI  - Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of
      cholinesterase activity, beta-amyloid aggregation and Ca2+ overload.
AB  - In this study, a series of multipotent phenylthiazole-tacrine hybrids (7a-7e, 8,
      and 9a-9m) were synthesized and biologically evaluated. Screening results showed
      that phenylthiazole-tacrine hybrids were potent cholinesterase inhibitors with
      pIC(50) (-logIC(50)) value ranging from 5.78 +/- 0.05 to 7.14 +/- 0.01 for
      acetylcholinesterase (AChE), and from 5.75 +/- 0.03 to 10.35 +/- 0.15 for
      butyrylcholinesterase (BuChE). The second series of phenylthiazole-tacrine
      hybrids (9a-9m) could efficiently prevent Abeta(1-42) self-aggregation. The
      structure-activity relationship revealed that their inhibitory potency relied on
      the type of middle linker and substitutions at 4'-position of 4-phenyl-2
      aminothiazole. In addition, 7a and 7c also displayed the Ca(2+) overload blockade
      effect in the primary cultured cortical neurons. Consequently, these compounds
      emerged as promising molecules for the therapy of Alzheimer's disease.

PMID- 23000297
TI  - Carbohydrate recognition by pentadecapeptide ligands for a series of sialylated
      oligosaccharides.
AB  - Sialyloligosaccharides of glycoproteins and glycosphingolipids play important
      roles in biological events on cell membranes. GT1b is a ganglioside having a
      trisialyloligosaccharide and is a receptor for tetanus toxin. In the present
      study, pentadecapeptide ligands for GT1b were obtained by phage display selection
      from a random peptide library with the use of a GT1b monolayer. The artificial
      pentadecapeptides had high affinity for GT1b which tended to increase depending
      on the number of sialic acids in sialyloligosaccharides. Arg, Ser, and
      hydrophobic amino acids were found in a consensus motif and may contribute to
      carbohydrate recognition. The consensus motif of the GT1b-binding peptides was
      different from that of GM1-, GM2-, GM3-, or GD1a-binding peptides. Peptide
      ligands for GT1b should be investigated for trisialyloligosaccharide functions
      and the development of therapeutic agents against trisialyloligosaccharide
      related diseases.

PMID- 23000298
TI  - Non-homogeneous effect of levodopa on inhibitory circuits in Parkinson's disease
      and dyskinesia.
AB  - INTRODUCTION: Levodopa-induced dyskinesia in patients with Parkinson's disease
      (PD) has been shown to be associated with an abnormal plasticity in the motor
      cortex. We investigated whether changes in the excitability of inhibitory and
      excitatory motor circuits could underlie maladaptive mechanisms associated with
      dyskinesia. METHODS: Using single and paired transcranial magnetic stimulation
      (TMS), we studied motor threshold, silent period (SP) duration, intracortical
      facilitation (ICF), short intracortical inhibition (SICI) and low- and high
      intensity long intracortical inhibition (LICI) in 10 dyskinetic and 10 non
      dyskinetic patients, matched for disease and treatment duration, before (OFF
      state) and after (ON state) levodopa, and in 10 healthy controls. RESULTS: In the
      OFF state, the two groups of patients showed similar motor cortex excitability
      with a reduced SICI compared to controls. LICI was weaker and increasing
      stimulation intensity had a lower effect on SP duration in dyskinetic patients
      than in controls. In dyskinetic patients, in contrast to non-dyskinetic patients,
      levodopa failed to increase SICI and SP duration, and potentiated to a lesser
      extent the effect of increasing the stimulation intensity on LICI. Although
      levodopa improved motor symptoms to a similar extent in both dyskinetic and non
      dyskinetic patients, it failed to activate effectively the excitability of the
      inhibitory systems in dyskinetic patients. DISCUSSION: These findings suggest
      that dyskinesia is associated with an abnormal effect of levodopa on cortical
      motor inhibitory circuits.

PMID- 23000299
TI  - Preclinical and clinical neural network changes in SCA2 parkinsonism.
AB  - BACKGROUND: The pathophysiological changes before the presentation of clinical
      symptoms in parkinsonism are unclear. In this study, we investigated neural
      network modulations in persons in the preclinical stage of familial parkinsonism,
      and how the network interactions change at the clinical stage. METHODS: We
      performed functional MRI in a family with SCA2 mutation, including 9 asymptomatic
      carriers and 10 mutation carriers with parkinsonian symptoms. Functional
      connectivity from the posterior putamen bilaterally and rostral supplementary
      motor area was used to explore network interactions in the subjects. RESULTS:
      Both the asymptomatic carriers and patients had decreased connectivity within the
      basal ganglia-thalamus-cortical motor loop compared to controls. The asymptomatic
      carriers showed extensively increased connectivity compared to controls,
      including the cortico-cortical motor, cortico-cerebellar, cortico-brainstem, and
      part of the basal ganglia-thalamus-cortical motor circuits. In contrast, the
      connectivity of most of these networks was decreased in the patients. These
      abnormalities were relatively normalized after levodopa administration.
      CONCLUSIONS: In the preclinical stage of SCA2 parkinsonism, the connectivity of a
      part of the basal ganglia motor loop is weakened as a consequence of dopaminergic
      deficits; meanwhile, the connectivity of other large-scale brain networks is
      strengthened presumably to compensate for the dysfunction of the basal ganglia to
      maintain brain function in the early stage of dopaminergic deficits. The
      simultaneous effects of progressive disruption of basal ganglia motor circuits
      and failure of compensatory mechanisms as dopaminergic dysfunction progresses may
      contribute to the onset of clinical symptoms.

PMID- 23000300
TI  - Confounders of excessive brain volume loss in schizophrenia.
AB  - There is convincing evidence that schizophrenia is characterised by progressive
      brain volume changes during the course of the illness. In a large longitudinal
      study it was shown that different age-related trajectories of brain tissue loss
      are present in patients compared to healthy subjects, suggesting that brain
      maturation that occurs in the third and fourth decade of life is abnormal in
      schizophrenia. However, studies show that medication intake and cannabis use are
      important confounding factors when interpreting brain volume (change)
      abnormalities. Indeed, continues use of cannabis, but not cigarette smoking, is
      associated to a more pronounced loss of grey matter in the anterior cingulated
      and the prefrontal cortex. Atypical antipsychotics have been found to be related
      to smaller decreases in tissue loss. Moreover, independent of antipsychotic
      medication intake, the brain volume abnormalities appear associated to the
      outcome of the illness.

PMID- 23000301
TI  - CD4+CD25+ Treg derived from hepatocellular carcinoma mice inhibits tumor
      immunity.
AB  - CD4+CD25+ regulatory T cells (Tregs) play an essential role in the establishment
      and persistence of tumor immune suppression. Tregs can prevent anti-tumor
      specific T cells from clearing the tumor, making Tregs a significant barrier for
      effective immunotherapy. An increase in the number of Tregs has been detected in
      the peripheral blood and tumor infiltrating lymphocytes of patients with
      hepatocellular carcinoma. Dendritic cells (DCs) are antigen-presenting cells that
      play a pivotal role in the initiation of immune responses. The evidence for their
      ability to act as natural adjuvant in the stimulation of specific anti-tumor
      cytotoxic T lymphocytes and in the induction of protective and therapeutic anti
      tumor immunity is now overwhelming. The aim of our study was to investigate the
      variation of Tregs in hepatocellular carcinoma mice and how Tregs derived from
      the tumor mice affect DCs' function. We found that Tregs derived from the tumor
      mice down-regulated the expression of costimulatory molecules CD80/CD86 on DCs
      and inhibited the production of TNF-alpha and IL-12 from DCs. The suppressive
      function of Tregs was mediated by cell-to-cell contact, CTLA-4 expression and IL
      10 secretion. In conclusion, these mechanisms acting in hepatocellular carcinoma
      may be necessary to better understand the immunosuppression of Tregs and helpful
      to the tumor immunotherapy.

PMID- 23000303
TI  - PEGylation of a proprotein convertase peptide inhibitor for vaginal route of drug
      delivery: in vitro bioactivity, stability and in vivo pharmacokinetics.
AB  - Uterine proprotein convertase (PC) 6 is critical for embryo implantation in mice
      and women. It is also one of the PC family members that play a vital role in HIV
      infectivity. We hypothesized that inhibiting PC6 in the female reproductive tract
      (vagina, cervix and uterus), may protect women from both pregnancy and HIV
      infection. One key requirement to prove this concept in an animal model is a
      vaginally deliverable PC6 inhibitor. Nona-D-arginine (Poly R) is a potent peptide
      PC inhibitor and is able to inhibit HIV in cell culture. We modified Poly R by
      PEGylation with different strategies and determined their biochemical properties
      in vitro and in vivo. PEGylation at the C-terminus, regardless of the PEG size
      (30 kDa or 1239 Da) did not compromise the inhibitory potency of Poly R. In
      contrast, PEGylation at both termini (1239 Da) dramatically reduced its
      inhibitory activity. Poly R and C-PEGylated Poly Rs also showed equal potency in
      inhibiting a PC6-dependent cellular process critical for embryo implantation.
      Poly R and the equipotent C-PEGylated Poly Rs were further tested for their serum
      stability in vitro and pharmacokinetics in vivo following vaginal administration
      in mice. All Poly Rs were equally stable in mouse serum in vitro for 24h; C
      PEGylated Poly Rs showed enhanced vaginal absorption and penetration across the
      vaginal mucosa/epithelium. This is the first report that C-terminal PEGylation
      significantly enhances the therapeutic properties of Poly R for vaginal drug
      delivery. Our findings also provide important insights into future design of Poly
      R derivatives.

PMID- 23000302
TI  - Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of
      resistance exercise.
AB  - AMP-activated protein kinase (AMPK) is a key energy-sensitive enzyme that
      controls numerous metabolic and cellular processes. Mammalian target of rapamycin
      (mTOR) is another energy/nutrient-sensitive kinase that controls protein
      synthesis and cell growth. In this study we determined whether older versus
      younger men have alterations in the AMPK and mTOR pathways in skeletal muscle,
      and examined the effect of a long term resistance type exercise training program
      on these signaling intermediaries. Older men had decreased AMPKalpha2 activity
      and lower phosphorylation of AMPK and its downstream signaling substrate acetyl
      CoA carboxylase (ACC). mTOR phosphylation also was reduced in muscle from older
      men. Exercise training increased AMPKalpha1 activity in older men, however,
      AMPKalpha2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not
      affected. In conclusion, older men have alterations in the AMPK-ACC and mTOR
      pathways in muscle. In addition, prolonged resistance type exercise training
      induces an isoform-selective up regulation of AMPK activity.

PMID- 23000304
TI  - Enhanced expression of human beta-defensin 2 in peripheral lungs of patients with
      chronic obstructive pulmonary disease.
AB  - Human beta-defensin 2 (hBD-2) has antimicrobial activity and may play a role in
      airway mucosal defense, but studies have not yet examined its expression in lung
      tissue of patients with chronic obstructive pulmonary disease (COPD). Here we
      investigated hBD-2 levels in lung tissues of COPD patients and analyzed their
      correlations with IL-8, IL-1beta, cigarette smoking and lung function in order to
      see whether the protein may be involved in pathogenesis of the disease.
      Peripheral lung tissue specimens were obtained from 51 patients who underwent
      lung resection for peripheral lung cancer: healthy non-smokers (n=8), healthy
      current smokers (n=7), non-smokers with COPD (n=11), and current smokers with
      COPD (n=25). RT-PCR and immunohistochemical staining were used to detect
      expression levels of hBD-2, IL-8 and IL-1beta. Expression of hBD-2 mRNA was
      significantly higher in COPD patients than in healthy controls, and significantly
      higher in current smokers than in non-smokers (p<0.05). Among healthy controls,
      hBD-2 mRNA levels were similar between current smokers and non-smokers.
      Immunohistochemistry showed hBD-2 protein to be expressed mainly in epithelia of
      distal bronchioles and its expression pattern among our patient groups mirrored
      that of the mRNA. IL-8 mRNA levels were significantly higher in COPD patients
      than in healthy controls (p<0.05), while IL-1beta mRNA levels did not differ
      significantly among the groups. Levels of hBD-2 mRNA positively correlated with
      levels of IL-8 mRNA (r=0.545, p=0.002), and negatively correlated with FEV1/FVC
      ratios and with predicted FEV1% values (r=-0.406, p=0.011). Our results indicate
      that hBD-2 expression is elevated in distal airways of COPD patients and that it
      may be involved in pathogenesis of the disease. Our data implicate cigarette
      smoking as a factor that may elevate hBD-2 levels in lung tissues of COPD
      patients.

PMID- 23000305
TI  - Antioxidant activity of vasoactive intestinal peptide in HK2 human renal cells.
AB  - Oxidative stress is a major mediator of tissue and cell injuries. The injury in
      chronic nephrotic syndrome, acute renal failure, myeloma kidney injury and other
      kidney diseases is initiated by oxidative stress. We have previously demonstrated
      that vasoactive intestinal peptide (VIP) acts as an antiproliferative agent in
      renal cancer cells. This study was designed to evaluate the renoprotective
      activity of VIP against H(2)O(2)-induced oxidative damage in a proximal tubule
      kidney cell line (human, non-tumor, HK2 cells) in order to investigate the
      potential usefulness of this peptide in the treatment of oxidative-stress related
      kidney diseases. HK2 cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide assay. Propidium iodide was used to identify
      cells undergoing apoptosis. Western blotting was performed with anti-Bcl-2, anti
      Bax and anti-formyl peptide receptor (low-affinity variant FPRL-1) monoclonal
      antibodies whereas 2,7-dichlorofluorescein diacetate was used for measurement of
      levels of intracellular reactive oxygen species (ROS). HK2 cells were injured
      with H(2)O(2) in order to induce apoptosis: the effect was time- and dose
      dependent. VIP increased the levels of the antiapoptotic protein Bcl-2 and
      decreased those of the proapoptotic protein Bax. VIP decreased the intracellular
      ROS levels reached by H(2)O(2)-induced oxidative stress. VIP effect on ROS levels
      involved FPLR-1 but not VPAC(1,2) receptors as evidenced by the use of the
      respective antagonists WRW4 and JV-1-53. Thus, VIP protects HK2 cells from
      apoptosis by increasing Bcl-2 levels and this effect is initiated through FPLR1
      receptor. In conclusion, VIP might exert a renoprotective effect by the
      suppression of oxidative stress.

PMID- 23000306
TI  - Molecular cloning of skin peptide precursor-encoding cDNAs from tibial gland
      secretion of the Giant Monkey Frog, Phyllomedusa bicolor (Hylidae, Anura).
AB  - The skins of phyllomedusine frogs have long been considered as being tremendously
      rich sources of bioactive peptides. Previous studies of both peptides and cloning
      of their precursor encoding cDNAs have relied upon methanolic skin extracts or
      the dissected skins of recently deceased specimens and have not considered the
      different glands in isolation. We therefore focused our attention on the tibial
      gland of the Giant Monkey Frog, Phyllomedusa bicolor and constructed a cDNA
      library from the skin secretion that was obtained via mechanical stimulation of
      this macrogland. Using shotgun cloning, four precursors encoding host-defense
      peptides were identified: two archetypal dermaseptins, a phyllokinin and a
      phylloseptin that is new for this species but has been recently described from
      the Waxy Monkey Leaf Frog, Phyllomedusa sauvagii. Our study is the first to
      report defensive peptides specifically isolated from anuran tibial glands,
      confirming the hypothesis that these glands also contribute to chemical defense.
      Moreover, the discovery of novel compounds for this otherwise very well
      characterized species suggests that this largely neglected gland might possess a
      different cocktail of secretions from glands elsewhere in the same animal. We
      will also discuss some evolutionary implications of our findings with respect to
      the adaptive plasticity of secretory glands.

PMID- 23000307
TI  - The expression of PAC1 increases in the degenerative thymus and low dose PACAP
      protects female mice from cyclophosphamide induced thymus atrophy.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with
      cytoprotective ability mediated by its specific receptor PAC1. In this research,
      firstly the thymus index and the expression of PAC1 in the normal and
      degenerative thymus with different gender were assayed; secondly PACAP in
      different dose was used to treat the female mice with cyclophosphamide (CPS) and
      the changes in thymus index, the expression of PAC1, histopathology, apoptosis,
      oxidative status and the caspase 3 activity in thymus were determined and
      compared. It was found that in the mice of age from 1 to 9 weeks in the stage of
      sex development, the thymus index was significantly higher in female mice than in
      male mice. And it was found for the first time that the PAC1 expression level in
      thymus of female mice was significantly higher than that of male mice and the
      expression of the PAC1 and PACAP increased significantly in the degenerative
      thymus induced by CPS. After PACAP was co-injected with CPS to the female mice,
      it was shown that only low dose (1 nmol/kg) of PACAP promoted the thymus index,
      inhibited the cell apoptosis, ameliorated the oxidative status and decreased the
      caspase activity significantly, while high dose (10 nmol/kg) of PACAP had no
      significant protective effects against CPS-induced thymus atrophy. It was
      concluded that the expression of PAC1 in the thymus changes in reverse ratio with
      thymus index and in direct ratio with cell apoptosis and only low dose of PACAP
      had positive effects against the CPS-induced thymus atrophy.

PMID- 23000308
TI  - Mitochondrial recombination in natural populations of the button mushroom
      Agaricus bisporus.
AB  - In the majority of sexual eukaryotes, the mitochondrial genomes are inherited
      uniparentally and have predominantly clonal population structures. In clonally
      evolving genomes, alleles at different loci will be in significant linkage
      disequilibrium. In this study, the associations among alleles at nine
      mitochondrial loci were analyzed for 379 isolates in four natural populations of
      the button mushroom Agaricus bisporus. The results indicated that the
      mitochondrial genome in the Desert California population was not significantly
      different from random recombination. In contrast, the three other populations all
      showed predominantly clonal mitochondrial population structure. While no evidence
      of recombination was found in the Alberta, Canada A. bisporus population,
      signatures of recombination were evident in the Coastal Californian and the
      French populations. We discuss the potential mechanisms that could have
      contributed to the observed mitochondrial recombination and to the differences in
      allelic associations among the geographic populations in this economically
      important mushroom.

PMID- 23000309
TI  - Application of microchip phosphate-affinity electrophoresis to measurement of
      protease activity in complex samples.
AB  - We previously demonstrated microchip phosphate-affinity electrophoresis (MUPAE)
      for activity measurement of kinases and phosphatases. In the current work, we
      extend the MUPAE application to a protease: caspase-3 (CASP3). We designed a
      substrate peptide modified with both a fluorescent tag for label and a phosphate
      tag for separation. The CASP3 cleavage reaction split the two tags and made the
      fluorescent fragment migrate electrophoretically. The CASP3 activity was
      correlated with the amount of the migrating fragment. This assay was proven to be
      compatible with a crude cell lysate.

PMID- 23000310
TI  - Multiplex-microsphere-quantitative polymerase chain reaction: nucleic acid
      amplification and detection on microspheres.
AB  - We report the development of a new system to monitor the amplification of nucleic
      acids on microspheres. This was realized by the design of (i) a "universal"
      oligonucleotide "tagged" polymerase chain reaction (PCR) forward primer, (ii) a
      sensor sequence complementary to the universal sequence on the forward PCR primer
      modified with a fluorescent dye, and (iii) a universal oligonucleotide coupled to
      Luminex microspheres. The PCR takes place with the microspheres present in the
      reaction tube. With the consumption of the universal oligonucleotide tagged
      forward primer, the fluorescently labeled sequences can bind to the universal
      oligonucleotide on the microspheres. We tested the microsphere quantitative PCR
      system with up to three different target genes (Neisseria meningitides porA and
      ctrA and influenza A M gene segment) as templates in a single PCR tube. The
      analytical sensitivity of this quantitative PCR system was tested and compared
      with the TaqMan system. The multiplex-microsphere-quantitative PCR system does
      not require design of unique internal probes for each target and has potential
      for a high degree of multiplexing, greater than the limited multiplexing
      achievable with current real-time protocols.

PMID- 23000311
TI  - Development of a novel enzyme-linked immunosorbent assay (ELISA) for measurement
      of serum CTRP1: a pilot study: measurement of serum CTRP1 in healthy donors and
      patients with metabolic syndrome.
AB  - BACKGROUND: Complement C1q tumor necrosis factor-related protein 1 (CTRP1), a
      recently identified adipokine, was found to stimulate aldosterone production.
      Obesity and metabolic syndrome are frequently associated with elevated levels of
      aldosterone. Therefore, it would be interesting to investigate whether the
      secretion of CTRP1 in human serum is associated with obesity as well as with
      hypertension. AIM: This study evaluated serum CTRP1 concentrations in healthy
      individuals and patients with metabolic syndrome. METHODS: Serum samples from 61
      healthy individuals and 46 patients with metabolic syndrome were measured for
      CTRP1 by enzyme-linked immunosorbent assay (ELISA). RESULTS: Correlation analyses
      showed that serum CTRP1 in healthy individuals did not correlate with BMI,
      leptin, TG, HDL-CH, and LDL-CH; however, in patients with metabolic syndrome,
      CTRP1 correlated with glucose, HbA1c and BMI. CTRP1 level was significantly
      higher in subjects with metabolic syndrome compared to healthy subjects.
      DISCUSSION: Our results support the hypothesis that adipokine CTRP1 is associated
      with metabolic syndrome and obesity compared to healthy individuals.

PMID- 23000312
TI  - Biological variation of neuroendocrine tumor markers chromogranin A and neuron
      specific enolase.
AB  - OBJECTIVES: Chromogranin A (CgA) and neuron-specific enolase (NSE) are biomarkers
      for neuroendocrine tumors. Although the knowledge of their biological variation
      (BV) is critical, only one study for CgA and no data for NSE are available. We
      report a definitive assessment of BV components of these biomarkers in the same
      cohort of subjects by an accurately experimental protocol. DESIGN AND METHODS: We
      collected five blood specimens from each of 22 healthy volunteers (10 men and 12
      women, 23-54 years) on the same day every two weeks for two months. Serum
      specimens were stored at -80  degrees C until analysis and analyzed in a single
      run in duplicate. Data were analyzed by ANOVA. RESULTS: Serum CgA concentrations
      were significantly higher for women than for men (P=0.01), whereas no difference
      was found for NSE. Intra-individual variance was not different between genders
      for both biomarkers. Within- and between-subject CVs were 16.3% and 33.5% for CgA
      and 13.6% and 11.5% for NSE, respectively. CgA showed marked individuality,
      suggesting that the use of population-based reference limits is inadequate for
      its interpretation. Conversely, the low individuality of NSE allows the use of a
      single reference interval. Reference change values were 46% for CgA and 39% for
      NSE. Desirable analytical goals for imprecision, bias, and total error were
      <8.2%, +/-9.3%, and +/-22.8% for CgA, and <6.8%, +/-4.5%, and +/-15.7% for NSE,
      respectively. CONCLUSION: In this study, we defined BV components of serum CgA
      and NSE and derived indices that may improve the clinical use of these
      biomarkers.

PMID- 23000313
TI  - Symptomatic venous thromboembolism in elderly patients following major orthopedic
      surgery of the lower limb is associated with elevated vitamin B12 serum levels.
AB  - BACKGROUND: Elevated vitamin B12 serum levels are associated with systemic
      inflammation and mortality. Since venous thromboembolism (VTE) is associated with
      systemic inflammation and mortality as well, we have hypothesized that it is also
      associated with elevated vitamin B12 serum levels in elderly patients following
      major orthopedic surgery of the lower limb. METHODS: This is a retrospective
      study. Medical charts of consecutive elderly (>=65 years) patients admitted for
      rehabilitation following major orthopedic surgery of the lower limb during 2007
      2009 were reviewed. The study group included symptomatic VTE patients. The
      control group included patients in whom VTE was excluded. Demographics, co
      morbidities, VTE risk factors, vitamin B12 serum levels, and 1-year mortality
      were studied. RESULTS: The cohort included 197 elderly patients (median age: 82
      years): 140 (71.1%) women and 57 (28.9%) men. Overall, 20 (10.2%) patients had
      VTE (study group) and in 177 (89.8%) patients VTE was excluded (control group).
      Vitamin B12 serum levels were higher in the study group compared with the control
      group (median: 634 vs. 409 pg/dL, p=0.024). The incidence of elevated vitamin B12
      serum levels (>=500 pg/dL) was higher in the study group compared with the
      control group (odds ratio 3.1, p=0.031). Elevated vitamin B12 serum levels were
      associated with VTE (odds ratio 5.3, p=0.011) and with 1-year mortality (odds
      ratio 6.6, p=0.015) independent of demographics, co-morbidities, and VTE risk
      factors. CONCLUSIONS: Symptomatic VTE is associated with elevated vitamin B12
      serum levels in elderly patients following major orthopedic surgery of the lower
      limb.

PMID- 23000314
TI  - Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH
      mutations in a Hong Kong chinese patient: recommendation for expanded newborn
      screening in Hong Kong.
AB  - OBJECTIVES: Tyrosinemia type I is an autosomal recessive disorder in tyrosine
      metabolism. In areas without expanded newborn screening, patients present with
      acute hepatorenal failure in early infancy. Diagnosis can be elusive when
      clinical presentation is non-specific and biochemical abnormalities are masked by
      secondary changes. This is the first Hong Kong Chinese report. DESIGN AND
      METHODS: A two-month-old Chinese male infant with unremarkable antenatal and
      postnatal history presented with progressive abdominal distension for three days.
      He suffered from end-stage liver failure, hypoglycemia and hepatic
      encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis,
      intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to
      metabolic diseases. Clinical, biochemical and genetic data was described.
      RESULTS: The patient showed increases in multiple plasma amino acids including
      tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl
      acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen
      in liver failure due to both tyrosinemia type I and non-metabolic conditions.
      Because of the volatile nature, succinylacetone was almost undetectable. The
      diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz.
      NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver
      transplantation was done. However, the patient still suffered many complications
      after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral
      atrophy, global developmental delay and cortical visual impairment. CONCLUSIONS:
      Because of the lack of expanded newborn screening in Hong Kong, this child
      unfortunately presented in the most severe form of tyrosinemia type I. Expanded
      newborn screening can save life and reduce the burden of diagnostic complexity.
      This illustrates the need for expanded newborn screening in Hong Kong.

PMID- 23000315
TI  - Purine metabolites in fibromyalgia syndrome.
AB  - OBJECTIVE: To evaluate serum purine metabolite concentrations in patients
      affected by fibromyalgia syndrome (FMS) and the relationships between their
      levels and FM clinical parameters. DESIGN AND METHODS: Serum purine levels were
      quantified using LC/UV-vis in 22 fibromyalgic females (according to the American
      College of Rheumatology classification criteria) and 22 healthy females. RESULTS:
      Significantly higher serum inosine, hypoxanthine and xanthine levels (p<0.001)
      and significantly lower serum adenosine (p<0.05) were detected in the FMS
      patients vs healthy controls. Our data show a negative correlation between
      adenosine and Fibromyalgia Impact Questionnaire (FIQ). CONCLUSIONS: Study results
      suggest that purines, in particular adenosine and inosine, may be involved in
      pain transmission in fibromyalgia.

PMID- 23000316
TI  - The role of feed regulating peptides on weight loss in patients with pulmonary
      tuberculosis.
AB  - PURPOSE: Malnutrition is a prominent feature of tuberculosis (TB). The aim of our
      study was to explore the function of plasma regulatory proteins in pulmonary TB
      and to investigate the relationship between these parameters and loss of body
      weight. METHODS: Plasma levels of fasting insulin, leptin, ghrelin, adiponectin
      and orexin-A were measured in 23 pulmonary TB patients, 39 patients with
      pulmonary sarcoidosis, 22 patients with different diffuse interstitial lung
      diseases and 21 healthy patients serving as controls. RESULT: Plasma leptin
      (p<0.001) and orexin-A (p<0.01) levels were significantly decreased in TB
      patients compared with those of the other study subjects. TB patients also had
      higher levels of plasma ghrelin compared with those of the other study subjects,
      while sarcoidosis patients had higher plasma adiponectin levels than the other
      study subjects. Glucose levels were similar in all groups, yet, insulin and
      Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) levels were
      significantly higher in the TB group compared to the other study groups. There
      was no correlation between leptin, ghrelin, adiponectin and orexin-A and other
      parameters. CONCLUSIONS: These data suggest that leptin and orexin-A levels have
      effects on weight loss in patients with pulmonary tuberculosis. Particularly,
      leptin may play a role in the early immune response to pulmonary TB and prolonged
      inflammation may further suppress leptin production. Measurement of HOMA-IR can
      indeed be used as a marker for the risk of activated TB. Further clinical studies
      are needed to better understand the role of feed regulating proteins in pulmonary
      tuberculosis.

PMID- 23000318
TI  - Thymidine glycol: the effect on DNA molecular structure and enzymatic processing.
AB  - Thymine glycol (Tg) in DNA is a biologically active oxidative damage caused by
      ionizing radiation or oxidative stress. Due to chirality of C5 and C6 atoms, Tg
      exists as a mixture of two pairs of cis and trans diastereomers: 5R cis-trans
      pair (5R,6S; 5R,6R) and 5S cis-trans pair (5S,6R; 5S,6S). Of all the modified
      pyrimidine lesions that have been studied to date, only thymine glycol represents
      a strong block to high-fidelity DNA polymerases in vitro and is lethal in vivo.
      Here we describe the preparation of thymine glycol-containing oligonucleotides
      and the influence of the oxidized residue on the structure of DNA in different
      sequence contexts, thymine glycol being paired with either adenine or guanine.
      The effect of thymine glycol on biochemical processing of DNA, such as
      biosynthesis, transcription and repair in vitro and in vivo, is also reviewed.
      Special attention is paid to stereochemistry and 5R cis-trans epimerization of
      Tg, and their relation to the structure of DNA double helix and enzyme-mediated
      DNA processing. Described here are the comparative structure and properties of
      other forms of pyrimidine base oxidation, as well as the role of Tg in tandem
      lesions.

PMID- 23000317
TI  - The paradox of ApoA5 modulation of triglycerides: evidence from clinical and
      basic research.
AB  - Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), even
      though its plasma concentration is very low compared to other known apoproteins.
      Over the years, researchers have attempted to elucidate the molecular mechanisms
      by which ApoA5 regulates plasma TG in vivo. Though still under debate, two
      theories broadly describe how ApoA5 modulates TG levels: (i) ApoA5 enhances the
      catabolism of TG-rich lipoproteins and (ii) it inhibits the rate of production of
      very low-density lipoprotein (VLDL), the major carrier of TGs. This review will
      summarize the basic and clinical studies that describe the importance of ApoA5 in
      TG metabolism. Population studies conducted in various countries have
      demonstrated an association between single nucleotide polymorphisms (SNPs) in
      ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome
      (including diabetes and obesity). ApoA5 is also highly expressed during liver
      regeneration and is an acute phase protein associated with HDL, which is
      independent of its effects on TG metabolism. CONCLUSION: Despite considerable
      evidences available from clinical and basic research studies on the role of ApoA5
      in TG metabolism and its indirect link to metabolic diseases, additional
      investigations are needed to understand the paradoxical role of this important
      apoprotein is modulated by both diet and its polymorphism variants.

PMID- 23000319
TI  - Studies on the peptidase activity of transthyretin (TTR).
AB  - Transthyretin (TTR) is a plasma protein transporter of thyroxine (T(4)) and
      retinol and also has peptidase activity. In order to characterize TTR peptidase
      activity we used fluorescence resonance energy transfer (FRET) peptides derived
      from Abz-KLRSSK-Q-EDDnp and from two portion-mixing libraries as substrates. Most
      of the susceptible FRET peptides were cleaved at more than one peptide bond,
      without particular substrate specificity. The more relevant observation was that
      the peptides containing E or D were cleaved at only one peptide bond and TTR was
      competitively inhibited by glutathione analog peptide gamma-E-A-G-OH that
      contains two free carboxyl groups. The dependence on ionic interactions of TTR
      hydrolytic activity was confirmed by the large inhibitory effects of salt and
      ionic surfactants. TTR was not inhibited by any usual peptidase inhibitors,
      except by ortho-phenanthroline and EDTA. The mechanism of TTR catalysis was
      explored by the pH-profile of TTR hydrolytic activity in different temperatures
      and by proton inventory. The obtained pK and heat of ionization values suggest
      that a carboxylate and an ammonium group, possibly from a lysine side chain are
      involved. These results support the recently proposed inducible metalloprotease
      mechanism for TTR based on its 3D structure in presence of Zn(2+) and a series of
      point mutations [Liz et al., Biochem. J 443 (2012) 769-778].

PMID- 23000320
TI  - Gender differences in emergency stroke care and hospital outcome in acute
      ischemic stroke: a multicenter observational study.
AB  - BACKGROUND: We aimed to investigate the effect of gender difference on the
      accessibility to emergency care, hospital mortality and disability in acute
      stroke care. METHODS: This study was performed on a single-tiered basic emergency
      medical service with a comprehensive national health insurance. Demographic
      variables, risk factors, elapsed time intervals, performing diagnosis and
      treatment options, hospital mortality, and modified Rankin Scale of acute
      ischemic stroke during 2008 were collected. We modeled the multivariate
      regression analysis for gender differences on the accessibility, hospital
      mortality, and disability. The adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated adjusting for potential risk factors. RESULTS:
      The total number of patients was 6635. The time from symptom onset to emergency
      department (ED) arrival and to computed tomography or magnetic resonance imaging
      scan and from ED arrival to computed tomography or magnetic resonance imaging
      scan was significantly longer in women. No significant difference was found in
      either the time to intravenous thrombolysis or in the number of patients who
      received intravenous thrombolysis, anti-platelet therapy, anti-coagulation, or
      operation. The hospital mortality rate was higher in women (3.9%) than in men
      (2.9%) (P = .03). The increased disability was significantly higher in women
      (67.8%) than in men (65.1%) (P = .02). The hospital mortality and increased
      disability showed a non-significant difference between the 2 genders in the
      adjusted model (OR, 1.10; 95% CI, 0.74-1.64) and (OR, 1.11; 95% CI, 0.96-1.28),
      respectively. CONCLUSION: The adjusted model for risk factors showed no
      significant difference on hospital mortality and disability between the 2 genders
      for stroke patients.

PMID- 23000321
TI  - Predictors of in-person follow-up among subjects in an ED-based smoking cessation
      trial.

PMID- 23000322
TI  - Uncommon double fistula between sinus node arteries and right atrium in a patient
      with atypical chest pain.
AB  - The main coronary artery variants and anomalies are completely asymptomatic and
      are discovered incidentally or as they rise symptoms. Multidetector computed
      tomography coronary angiography represents an excellent technique for noninvasive
      assessment of the coronary tree mainly because of the multiplanar imaging
      modalities of computed tomography. Thin collimation permits to depict thin
      vessels such as the sinus node artery, as reported in this case. In this brief
      report, we describe a case of a rare anomaly of termination the coronaries, a
      double fistula between the sinus node artery, and the right atrium in a patient
      with atypical chest pain.

PMID- 23000323
TI  - Decision support system in prehospital care: a randomized controlled simulation
      study.
AB  - INTRODUCTION: Prehospital emergency medicine is a challenging discipline
      characterized by a high level of acuity, a lack of clinical information and a
      wide range of clinical conditions. These factors contribute to the fact that
      prehospital emergency medicine is a high-risk discipline in terms of medical
      errors. Prehospital use of Computerized Decision Support System (CDSS) may be a
      way to increase patient safety but very few studies evaluate the effect in
      prehospital care. The aim of the present study is to evaluate a CDSS. METHODS: In
      this non-blind block randomized, controlled trial, 60 ambulance nurses
      participated, randomized into 2 groups. To compensate for an expected learning
      effect the groups was further divided in two groups, one started with case A and
      the other group started with case B. The intervention group had access to and
      treated the two simulated patient cases with the aid of a CDSS. The control group
      treated the same cases with the aid of a regional guideline in paper format. The
      performance that was measured was compliance with regional prehospital guidelines
      and On Scene Time (OST). RESULTS: There was no significant difference in the two
      group's characteristics. The intervention group had a higher compliance in the
      both cases, 80% vs. 60% (p<0.001) but the control group was complete the cases in
      the half of the time compare to the intervention group (p<0.001). CONCLUSION: The
      results indicate that this CDSS increases the ambulance nurses' compliance with
      regional prehospital guidelines but at the expense of an increase in OST.

PMID- 23000324
TI  - LUCAS compared to manual cardiopulmonary resuscitation is more effective during
      helicopter rescue-a prospective, randomized, cross-over manikin study.
AB  - OBJECTIVE: High-quality chest-compressions are of paramount importance for
      survival and good neurological outcome after cardiac arrest. However, even
      healthcare professionals have difficulty performing effective chest-compressions,
      and quality may be further reduced during transport. We compared a mechanical
      chest-compression device (Lund University Cardiac Assist System [LUCAS]; Jolife,
      Lund, Sweden) and manual chest-compressions in a simulated cardiopulmonary
      resuscitation scenario during helicopter rescue. METHODS: Twenty-five advanced
      life support-certified paramedics were enrolled for this prospective, randomized,
      crossover study. A modified Resusci Anne manikin was employed. Thirty minutes of
      training was allotted to both LUCAS and manual cardiopulmonary resuscitation
      (CPR). Thereafter, every candidate performed the same scenario twice, once with
      LUCAS and once with manual CPR. The primary outcome measure was the percentage of
      correct chest-compressions relative to total chest-compressions. RESULTS: LUCAS
      compared to manual chest-compressions were more frequently correct (99% vs 59%, P
      < .001) and were more often performed correctly regarding depth (99% vs 79%, P <
      .001), pressure point (100% vs 79%, P < .001) and pressure release (100% vs 97%,
      P = .001). Hands-off time was shorter in the LUCAS than in the manual group (46
      vs 130 seconds, P < .001). Time until first defibrillation was longer in the
      LUCAS group (112 vs 49 seconds, P < .001). CONCLUSIONS: During this simulated
      cardiac arrest scenario in helicopter rescue LUCAS compared to manual chest
      compressions increased CPR quality and reduced hands-off time, but prolonged the
      time interval to the first defibrillation. Further clinical trials are warranted
      to confirm potential benefits of LUCAS CPR in helicopter rescue.

PMID- 23000325
TI  - Prospective study of violence against ED workers.
AB  - BACKGROUND: Health care support occupations have an assault-injury rate nearly 10
      times the general sector. Emergency departments (EDs) are at greatest risk of
      such events. OBJECTIVE: The objective was to describe the incidence of violence
      in ED health care workers (HCWs) over 9 months. Specific aims were to (1)
      identify demographic, occupational, and perpetrator factors related to violent
      events (VEs) and (2) identify predictors of acute stress in victims and
      predictors of loss of productivity. METHODS: A longitudinal, repeated-methods
      design was used to collect monthly survey data from ED HCWs at 6 hospitals.
      Surveys assessed number and type of VEs, and feelings of safety and confidence.
      Victims also completed specific VE surveys. Descriptive statistics and a repeated
      measure linear regression model were used. RESULTS: Two hundred thirteen ED HCWs
      completed 1795 monthly surveys and 827 VEs were reported. Average VE rate per
      person per 9 months was 4.15. Six hundred one events were physical threats (PTs)
      (3.01 per person). Two hundred twenty six events were assaults (1.13 per person).
      Five hundred one VE surveys were completed, describing 341 PTs and 160 assaults.
      Men perpetrated 63% of PTs and 52% of assaults. Significant differences in VEs
      were reported between registered nurses (RNs) and medical doctors (MDs) (P =
      .0017) and patient care assistants (P < .05). The RNs felt less safe than the MDs
      (P = .0041). The MDs felt more confident than the RNs in dealing with violent
      patients (P = .013). The RNs were more likely to experience acute stress than the
      MDs (P < .001). Acute stress reduced productivity (P < .001). CONCLUSION:
      Emergency department HCWs are frequent victims of violence perpetrated by
      visitors and patients. This results in injuries, acute stress, and lost
      productivity. Acute stress has negative consequences on workers' ability to
      perform their duties.

PMID- 23000326
TI  - A community-based comparison of trauma patient outcomes between D- and L-lactate
      fluids.
AB  - PURPOSE: Ringer's lactate is used for patient resuscitation. Lactate naturally
      occurs in 2 stereoisometric forms, D- and L-lactate, that are added to fluid in
      equal amounts. Animal studies have demonstrated potentially deleterious effects
      of d-lactate on vital organs. Using an administrative database, we examined
      whether D- or L-lactate volume was associated with mortality in patients with
      trauma. BASIC PROCEDURES: The Trauma and Injury Severity Score could be
      calculated in 24,616 of 528,219 patients admitted in 2006 to 2009. Demographic
      characteristics, the use of blood products, mechanical ventilation, and mortality
      were compared among the following 3 groups of patients administered Ringer's
      lactate: group 1, fluids other than Ringer's lactate; group 2, fluids including
      Ringer's DL-lactate; and group 3, no D-lactate. The mean volume (in millimoles
      per day) of D- and L-lactate administered was calculated. Multivariate analyses
      were used to measure the impact of lactate volume on mortality, and mechanical
      ventilation started more than 48 hours after admission. MAIN FINDINGS: Groups 2
      and 3 consisted of 2,827 (11.5%) patients (88 hospitals) and 12,036 (48.9%)
      patients (145 hospitals), respectively. The use of mechanical ventilation best
      explained the variation in mortality. Greater d-lactate volume, but not fluid
      management category or L-lactate volume, was associated with mortality. L-Lactate
      decreased and D-lactate increased the use of mechanical ventilation more than 48
      hours after admission. CONCLUSIONS: Because early administration of D-lactate was
      associated with mortality and ventilation, physicians and policy makers should
      recognize the advantages of L-lactate and encourage research on the quality of d-
      and l-lactate in case mixes beyond trauma.

PMID- 23000328
TI  - Comparison of risk scoring systems in predicting clinical outcome at upper
      gastrointestinal bleeding patients in an emergency unit.
AB  - BACKGROUND: Admission Rockall score (RS), full RS, and Glasgow-Blatchford
      Bleeding Score (GBS) can all be used to stratify the risk in patients presenting
      with upper gastrointestinal bleeding (UGIB) in the emergency department (ED). The
      aim of our study was to compare both admission and full RS and GBS in predicting
      outcomes at UGIB patients in a Romanian ED. PATIENTS AND METHODS: A total of 229
      consecutive patients with UGIB were enrolled in the study. Patients were followed
      up 60 days after admission to ED because of UGIB episode to determine cases of
      rebleeding or death during this period. By using areas under the curve (AUCs), we
      compared the 3 scores in terms of identifying the most predictive score of
      unfavorable outcomes. RESULTS: Rebleeding rate was 40.2% (92 patients), and
      mortality rate was 18.7% (43 patients). For the prediction of mortality, full RS
      was superior to GBS (AUC, 0.825 vs 0.723; P = .05) and similar to admission RS
      (AUC, 0.792). Glasgow-Blatchford Bleeding Score had the highest accuracy in
      detecting patients who needed transfusion (AUC, 0.888) and was superior to both
      the admission RS and full RS (AUC, 0.693 and 0.750, respectively) (P < .0001). In
      predicting the need for intervention, the GBS was superior to both the admission
      RS and full RS (AUC, 0.868, 0.674, and 0.785, respectively) (P < .0001 and P =
      .04, respectively). CONCLUSIONS: The GBS can be used to predict need for
      intervention and transfusion in patients with UGIB in our ED, whereas full RS can
      be successfully used to stratify the mortality risk in these patients.

PMID- 23000327
TI  - Proadrenomedullin, a useful tool for risk stratification in high Pneumonia
      Severity Index score community acquired pneumonia.
AB  - The aim of the present study was, first, to evaluate the prognostic value of mid
      regional proadrenomedullin (proADM) in emergency department (ED) patients with a
      diagnosis of community acquired pneumonia (CAP) and, second, to analyze the added
      value of proADM as a risk stratification tool in comparison with other biomarkers
      and clinical severity scores. We evaluated proADM, C-reactive protein and
      procalcitonin, along with the Pneumonia Severity Index (PSI) score in consecutive
      CAP patients. Ability to predict 30-day mortality was assessed using receiver
      operating characteristic curve analysis, logistic regression, and
      reclassification metrics for all patients and for patients with high PSI scores.
      Primary outcome was death within 30 days after ED admission. One hundred nine
      patients were included (median age [interquartile range] 71 [27] years). Nine
      patients died within 30 days. A significant correlation between proADM and PSI
      was found (rho = 0.584, P < .001). PSI and proADM levels were significantly
      predictive of risk of death. In patients with PSI class IV and V (score >90),
      proADM levels significantly predicted risk of death (OR [95% CI], 4.681 (1.661
      20.221), P = .012) whereas PSI score did not (P = .122). ROC(AUC) (area under the
      receiver operating characteristic curve) was higher for proADM than for PSI score
      (ROC(AUC) [95% CI], 0.810 [0.654-0.965] and 0.669 [0.445-0.893] respectively).
      Reclassification analysis revealed that combination of PSI and proADM allows a
      better risk assessment than PSI alone (P = .001). MR-proADM may be helpful in
      individual risk stratification of CAP patients with a high PSI score in the ED,
      allowing to a better identification of patients at risk of death.

PMID- 23000329
TI  - Characteristics and outcomes of injured patients presenting by private vehicle in
      a state trauma system.
AB  - BACKGROUND: Previous studies have demonstrated lower mortality among patients
      transported to single urban trauma centers by private vehicle (PV) compared with
      Emergency Medical Services (EMS). We sought to describe the characteristics and
      outcomes of injured patients transported by PV in a state trauma system compared
      to patients transported by EMS. METHODS: We performed a retrospective cohort
      study of state trauma registry data for patients admitted to all Pennsylvania
      trauma centers over 5 years (1/2003 to 12/2007). Our primary exposure of interest
      was prehospital mode of transport and our primary outcome of interest was in
      hospital mortality. Unadjusted analyses were performed as were adjusted analyses
      controlling for injury severity. Data are presented as percents, odds ratios
      (ORs), and 95% confidence intervals. RESULTS: Of the 91132 patients analyzed,
      9.6% were transported to the emergency department by PV and 90.4% by EMS. Overall
      Injury Severity Score (ISS) was 13.3 +/- 11.0 (ISS for EMS 13.7 +/- 11.3, PV 9.2
      +/- 7.1, P < .001), and 6.6% of patients died (EMS 7.1%, PV 1.5%, P < .001).
      After adjusting for injury severity, patients transported by EMS were more likely
      to die than PV patients (OR 1.9 [95% CI 1.5-2.4]). This effect persisted in
      blunt, penetrating, advanced life support, and basic life support subgroups, but
      not in the severely injured (ISS >15, ISS >25) subgroups. CONCLUSIONS: Nearly 10%
      of injured patients arrive at trauma centers by private vehicle. Transport of
      injured patients by EMS was associated with higher mortality than PV transport.
      This may reflect the effects of prehospital time, prehospital interventions, or
      other confounders.

PMID- 23000330
TI  - A new electrocardiogram finding for massive pulmonary embolism: ST elevation in
      lead aVR with ST depression in leads I and V(4) to V(6).

PMID- 23000331
TI  - Emergency medicine in China: current situation and its future development.

PMID- 23000332
TI  - The use of ondansetron for nausea and vomiting after head injury and its effect
      on return rates from the pediatric ED.
AB  - BACKGROUND: The use of ondansetron in children with vomiting after a head injury
      has not been well studied. Concern about masking serious injury is a potential
      barrier to its use. OBJECTIVE: The aim of this study was to evaluate the use of
      ondansetron in children with head injury and symptoms of vomiting in the
      pediatric emergency department (PED) and its effect on return rates and masking
      of more serious injuries. DESIGN/METHODS: Visits to 2 PEDs from 2003 to 2010 with
      a diagnosis of head injury were evaluated retrospectively. Patients discharged
      home after a head computed tomography (CT) are the primary cohort for the study.
      A logistic regression model was used to analyze ondansetron's effects on the
      likelihood of return to the PED within 72 hours for persistent symptoms. A
      secondary analysis was performed on patients with a diagnoses of head injury who
      did not receive a head CT and were discharged. RESULTS: A total of 6311 patients
      had a diagnosis of head injury, had a head CT performed, and were discharged from
      the PED. The use of ondansetron increased significantly from 3.7% in 2003 to 22%
      in 2010 (P < .001). After controlling for demographic/acuity differences,
      receiving ondansetron in the PED was associated with a lower likelihood of
      returning within 72 hours (0.49, 95% confidence interval [0.26-0.92]). In
      patients with head injury who did not have a head CT performed and were sent
      home, the use of ondansetron in the PED was not associated with an increased risk
      of missed diagnoses. CONCLUSION: Ondansetron use in children with a CT scan who
      are dispositioned home is relatively safe, does not appear to mask any
      significant conditions, and significantly reduces return visits to the PED.

PMID- 23000334
TI  - Subconjunctival hemorrhage in a patient on dabigatran (Pradaxa).

PMID- 23000335
TI  - The cause of paroxysmal atrial fibrillation: hyperbaric oxygen therapy or carbon
      monoxide poisoning?

PMID- 23000336
TI  - Different impact of the appropriateness of empirical antibiotics for bacteremia
      among younger adults and the elderly in the ED.
AB  - OBJECTIVES: To investigate the clinical impact of age on bacteremia among adults
      visiting the emergency department (ED). METHODS: Bacteremic adults visiting the
      ED from January 2008 to December 2008 were identified retrospectively.
      Demographic characteristics, severity, bacteremic pathogens with in vitro
      susceptibility, antimicrobial agents, and outcomes determined from chart records
      were analyzed as a case-control study. RESULTS: Of 518 eligible bacteremic
      adults, 288 (55.6%) elderly patients (>=65 years old) were case patients and 230
      younger patients (<65 years) were regarded as control patients. The 28-day
      mortality rate was higher in the case patients than that in the control patients
      (11.8% vs 6.1%, P = .02). The proportion of inappropriate empirical antibiotic
      therapy between the survivors and nonsurvivors was similar in control patients
      (69.4% vs 64.3%, P = .77); but for the case patients, the proportion of
      inappropriate empirical antibiotic therapy in the survivors was lower than that
      in the non-survivors (27.6% vs 44.1%, P = .04). Of note, inappropriate empirical
      antibiotic therapy was also one of independent risk factors of 28-day mortality
      by the multivariate analyses in the case patients (odds ratio [OR] 3.65; P =
      .049). Other independent predictors of 28-day mortality in case patients included
      a high Pittsburgh bacteremia score (>=4 points; OR 22.16; P < .001), bacteremia
      due to foci other than urinary tract infection (OR 9.07; P = .002), malignancy
      (OR 10.87; P < .001), coronary artery disease (OR 5.68; P = .01), and high serum
      creatinine (>1.5 mg/dL; OR 3.44; P = .04). CONCLUSIONS: For bacteremic adults,
      this study demonstrated the impact of inappropriate empirical antibiotic therapy
      on patients' outcome in the elderly was greater than that in the younger adults.

PMID- 23000337
TI  - Haploidentical hematopoietic stem cell transplantation for lymphoma with monosomy
      of chromosome 6 (loss of heterozygosity in the HLA region)--who should be a
      donor?
AB  - Hematopoietic stem cell transplantation (HSCT) from an HLA haploidentical family
      donor is an option for patients who do not have a full HLA matched donor and lack
      the time to find an unrelated one [1,2]. Furthermore, it may facilitate a
      powerful graft versus leukemia/lymphoma (GVL) effect to help combat hematological
      malignancies by directly targeting the mismatched HLA expressed on
      leukemia/lymphoma cells [3]. On the contrary, leukemia/lymphoma cells escape from
      the surveillance of the donor-derived GVL effect by losing the target HLA
      (mismatched HLA in GVH direction). This mechanism has been called loss of
      heterozygosity (LOH) in the HLA gene region on chromosome 6 [4,5]. Taking the
      above into account, in this case report, we present a case of lymphoma with
      monosomy 6, which means natural LOH of HLA, and suggest that selection of a
      haploidentical family donor matched with the missing HLA haplotype seems to be
      very effective.

PMID- 23000338
TI  - Crosstalk between VEGF and novel angiogenic protein regulates tumor angiogenesis
      and contributes to aggressiveness of breast carcinoma.
AB  - We have identified and characterized a novel proangiogenic glycoprotein (NAP)
      with molecular weight of 67 kDa from synovial fluid of rheumatoid arthritis
      patients. Proteomic analysis of the protein revealed 29% sequence coverage with
      maximum identity for human retinoblastoma binding protein 2. N-terminal amino
      acid sequence showed no identity to recently discovered protein sequences. NAP
      was also identified in both normal and tumor cell lines by Western blotting. NAP
      is a permeability factor as verified by miles permeability assay. The
      proangiogenic potential of NAP was identified using shell less CAM, rat cornea
      and tumor on CAM assays. NAP induces expression of VEGF and Flt-1 gene as
      verified by promoter reporter gene analysis. Further NAP induces proliferation of
      endothelial cells and formation of tube like structures. NAP is also involved in
      migration and invasion of tumor cells. Clinical data revealed the presence of NAP
      in breast cancer biopsies. We have developed monoclonal antibody (mAb), and
      specific ELISA, which confirmed the presence of NAP in the cytosol of tumor
      cells. The mAb effect was evaluated with established angiogenic assays. Further,
      we investigated the detailed mechanism by which NAP induces angiogenesis. NAP is
      phosphorylated by VEGF induced activation of MAPK and JNK pathways through VEGFR2
      phosphorylation. NAP involves JNK pathway predominantly with further activation
      of NFkappaB in downstream processing of VEGF activation. Together these findings
      establish that NAP displays angiogenic properties and promotes efficient
      neovascularization both in vitro and in vivo models. These observations suggest
      that anti-NAP-mAb can be targeted for antiangiogenic therapy of cancer.

PMID- 23000339
TI  - Feedforward and feedback regulation of the MAPK and PI3K oscillatory circuit in
      breast cancer.
AB  - Although the theoretical possibility of oscillations in MAPK signalling has long
      been described, experimental validation has proven more elusive. In this study we
      observed oscillations in MAPK and PI3K signalling in breast cancer cells in
      response to epidermal growth factor receptor-family stimulation. Using systems
      level analysis with a kinetic model, we demonstrate that receptor amplification,
      loss of transcriptional feedback, or pathway crosstalk, are responsible for
      oscillations in MAPK and PI3K signalling. Transcriptional profiling reveals
      architectural motifs likely to be responsible for feedback control of
      oscillations. Overexpression of the HER2 oncogene and inhibition of
      transcriptional feedback increase the amplitude of oscillations and provide
      experimental validation of the computational findings.

PMID- 23000340
TI  - Lithium enhances CRTC oligomer formation and the interaction between the CREB
      coactivators CRTC and CBP--implications for CREB-dependent gene transcription.
AB  - Lithium salts are important drugs to treat bipolar disorder. Previous work showed
      that lithium by enforcing the interaction between the transcription factor CREB
      and its coactivator CRTC1 enhanced cAMP-stimulated CREB-dependent gene
      transcription. Both CREB and CRTC have been implicated in neuronal adaptation,
      which might underlie lithium's therapeutic action. In the present study the
      mechanisms of lithium action on cAMP-induced CREB-dependent gene transcription
      were further elucidated. Transient transfection assays revealed that all three
      CRTC isoforms conferred lithium responsiveness to CREB whereas their intrinsic
      transcriptional activities remained unchanged by lithium, suggesting a
      conformational change of CREB or CRTC by lithium. In in vitro protein-protein
      interaction assays lithium enhanced the interaction between CREB and both
      coactivators CRTC and CBP. Furthermore, lithium enforced the oligomerization of
      CRTC, a prerequisite for CREB interaction. For further evaluation it was
      investigated whether lithium competes with magnesium, which coordinates the
      conformation of the CREB basic region leucine zipper (bZip). Mutational analysis
      of the magnesium coordinating lysine-290 within the bZip, in vitro and
      intracellular interaction assays and luciferase reporter-gene assays revealed
      that the effect of lithium on the CREB-CRTC interaction or on the transcriptional
      activity, respectively, was not affected by the mutation, thus excluding a
      magnesium-lithium competition. However, the CREB-CRTC interaction was strongly
      increased in lysine-290-mutants thereby extending the CRTC-CREB interaction
      domain. Taken together the results exclude a competition between lithium and
      magnesium at the bZip, but suggest that lithium by enforcing the CRTC-oligomer
      formation and the interaction of CREB-CBP-CRTC enhances cAMP-induced CREB
      dependent gene transcription.

PMID- 23000341
TI  - Identification of a Rho family specific guanine nucleotide exchange factor,
      FLJ00018, as a novel actin-binding protein.
AB  - FLJ00018/PLEKHG2 is a guanine nucleotide exchange factor for the Rho family small
      GTPases. FLJ00018 is directly activated by heterotrimeric G protein Gbetagamma
      subunits. Using two-hybrid screening, we have identified non-muscle cytosolic
      actin as a binding partner of FLJ00018. We found that there were two actin
      binding regions in FLJ00018 at the N-terminal region (150-283 amino acids) and at
      the C-terminal region (465-1386 amino acids). The overexpression of non-muscle
      cytosolic actin attenuated the FLJ00018-induced serum response element-dependent
      gene transcription. These results suggest that non-muscle cytosolic actin may be
      a negative regulator of FLJ00018 through its interaction with the Dbl homology
      domain.

PMID- 23000342
TI  - Nemo-like kinase, a multifaceted cell signaling regulator.
AB  - Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinase-related kinase.
      Although NLK was originally identified as a Drosophila gene affecting cell
      movement during eye development, recent studies show that NLK also contributes to
      cell proliferation, differentiation, and morphological changes during early
      embryogenesis and nervous system development in vertebrates. In addition, NLK has
      been reported to be involved in the development of several human cancers. NLK is
      able to play a role in multiple processes due to its capacity to regulate a
      diverse array of signaling pathways, including the Wnt/beta-catenin, Activin, IL
      6, and Notch signaling pathways. Although the molecular mechanisms that regulate
      NLK activity remain unclear, our recent research has presented a new model for
      NLK activation. Here, we summarize the current understanding of the function and
      regulation of NLK and discuss the aspects of NLK regulation that remain to be
      resolved.

PMID- 23000343
TI  - Starvation-induced autophagy is regulated by mitochondrial reactive oxygen
      species leading to AMPK activation.
AB  - Starvation is the most extensively studied condition that induces autophagy.
      Previous studies have demonstrated that starvation-induced autophagy is regulated
      by reactive oxygen species (ROS) such as superoxide (O(2)(.-)) but the source for
      ROS under starvation conditions and the downstream signaling pathways regulating
      autophagy are unclear. In this study, a cervical cancer HeLa cell line was
      generated that was deficient in mitochondrial electron transport chain (mETC)
      (HeLa rho degrees  cells). This resulted in endogenous levels of O(2)(.-) being
      significantly reduced and failed to be induced under starvation of glucose, L
      glutamine, pyruvate, and serum (GP) or of amino acids and serum (AA) compared to
      wild type (wt) HeLa cells. In contrast, H(2)O(2) production failed to increase
      under GP starvation in both wild type and rho degrees  cells whereas it increased
      in wt cells but not in rho degrees  cells under AA starvation. GP or AA
      starvation induced autophagy was blocked in rho degrees  cells as determined by
      the amount of autophagosomes and autolysosomes. Autophagy is regulated by 5'
      adenosine monophosphate-activated protein kinase (AMPK) activation and AMPK is
      activated under starvation conditions. We demonstrate that rho degrees  cells and
      HeLa cells over expressing manganese-superoxide dismutase 2 (SOD2) cells fail to
      activate AMPK activation following starvation. This indicates that mitochondrial
      ROS might regulate AMPK activation. In addition, inhibiting AMPK activation
      either by siRNA or compound C resulted in reduced autophagy during starvation.
      Using a ROS scavenger NAC, AMPK activation is reduced under starvation condition
      and mTOR signaling is increased. Taken together, mitochondria-generated ROS
      induces autophagy mediated by the AMPK pathway under starvation conditions.

PMID- 23000344
TI  - Ursolic acid induces ER stress response to activate ASK1-JNK signaling and induce
      apoptosis in human bladder cancer T24 cells.
AB  - Here we studied the cellular mechanisms of ursolic acid's anti-bladder cancer
      ability by focusing on endoplasmic reticulum stress (ER stress) signaling. We
      show that ursolic acid induces a significant ER stress response in cultured human
      bladder cancer T24 cells. ER stress inhibitor salubrinal, or PERK silencing,
      diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits
      ursolic acid-induced CHOP expression, Bim ER accumulation and caspase-3
      activation in T24 cells. Ursolic acid induces IRE1-TRAF2-ASK1 signaling complex
      formation to activate pro-apoptotic ASK1-JNK signaling. We suggest that ER stress
      contributes to ursolic acid's effects against bladder cancer cells.

PMID- 23000345
TI  - Aberrant association between vascular endothelial growth factor receptor-2 and VE
      cadherin in response to vascular endothelial growth factor-a in Shb-deficient
      lung endothelial cells.
AB  - Vascular permeability is a hallmark response to the main angiogenic factor VEGF-A
      and we have previously described a reduction of this response in Shb knockout
      mice. To characterize the molecular mechanisms responsible for this effect,
      endothelial cells were isolated from lungs and analyzed in vitro. Shb deficient
      endothelial cells exhibited less migration in a scratch wound-healing assay both
      under basal conditions and after vascular endothelial growth factor-A (VEGF-A)
      stimulation, suggesting a functional impairment of these cells in vitro. Staining
      for VE-cadherin and vascular endothelial growth factor receptor-2 (VEGFR-2)
      showed co-localization in adherens junctions and in intracellular sites such as
      the perinuclear region in wild-type and Shb knockout cells. VEGF-A decreased the
      VE-cadherin/VEGFR-2 co-localization in membrane structures resembling adherens
      junctions in wild-type cells whereas no such response was noted in the Shb
      knockout cells. VE-cadherin/VEGFR-2 co-localization was also recorded using
      spinning-disk confocal microscopy and VEGF-A caused a reduced association in the
      wild-type cells whereas the opposite pattern was observed in the Shb knockout
      cells. The latter expressed slightly more of cell surface VEGFR-2. VEGF-A
      stimulated extracellular-signal regulated kinase, Akt and Rac1 activities in the
      wild-type cells whereas no such responses were noted in the knockout cells. We
      conclude that aberrant signaling characteristics with respect to ERK, Akt and
      Rac1 are likely explanations for the observed altered pattern of VE
      cadherin/VEGFR-2 association. The latter is important for understanding the
      reduced in vivo vascular permeability response in Shb knockout mice, a phenomenon
      that has patho-physiological relevance.

PMID- 23000346
TI  - Signaling crosstalk of FHIT, CHK2 and p38 in etoposide induced growth inhibition
      in MCF-7 cells.
AB  - FHIT (Fragile Histidin Triad) is a tumor suppressor gene involved in regulating
      cell death during DNA damage conditions. The exact mechanism of DNA damage
      induced FHIT signaling is not well understood. It is known that p38 kinase and
      CHK2 kinase are being activated during stress-induced conditions and DNA damage,
      resulting in cell death. Since both CHK2 and FHIT are being influenced by DNA
      damage, we have evaluated the interplay of p38, CHK2 and FHIT in response to
      etoposide-induced cell death. DNA damage was induced by etoposide in MCF-7 cells
      and viability was examined using MTT. FHIT expression was blocked using siRNA.
      Protein expression was measured using western blotting. Our results indicated
      that etoposide induced cytotoxicity in MCF-7. Block of FHIT expression,
      completely reversed etoposide cytotoxicity. Besides, etoposide induced p38 and
      CHK2 phosphorylation and reduced FHIT expression in a time-dependent manner. The
      time-course study indicated that CHK2 had been phosphorylated prior to p38
      activation. Knockdown of FHIT expression reduced CHK2 phosphorylation but had no
      significant effect on p38 activation. Inhibition of p38 kinase and CHK2 prevented
      etoposide induced alteration in FHIT expression. Furthermore, p38 inhibitors
      augmented etoposide-induced CHK2 phosphorylation. These results indicate that
      etoposide lowers FHIT expression and induces cell death via p38 and CHK2
      phosphorylation. These results demonstrate a time dependent complex crosstalk of
      FHIT, p38 and CHK2 pathways in response to etoposide. Moreover, our findings
      suggest signaling interaction for these pathways which can be targeted for
      manipulating cell proliferation.

PMID- 23000347
TI  - Gender differences in partner influences and barriers to condom use among
      heterosexual adolescents attending a public sexually transmitted infection clinic
      in Singapore.
AB  - OBJECTIVE: To compare gender differences in the factors associated with condom
      use at most recent voluntary intercourse among heterosexual adolescents attending
      a public clinic for sexually transmitted infections (STIs). STUDY DESIGN: Between
      2008 and 2011, we conducted a cross-sectional survey on 964 never-married
      adolescents between 14 and 19 years of age who reported having engaged in
      voluntary intercourse for most recent sexual encounter and were attending the
      only public STI clinic in Singapore for screening or treatment of STIs. Data were
      collected using a self-administered questionnaire. RESULTS: The response rate to
      the questionnaire was 85.2%. In multivariate analysis, condom use at last
      intercourse for both genders was negatively associated with Malay race and peer
      connectedness and was positively associated with confidence in the ability to use
      a condom correctly. Being employed was positively associated with condom use for
      female respondents only. For male respondents only, condom use showed a positive
      association with living in better housing, older age at first intercourse, and
      engaging in sexual intercourse with commercial sex partners. Almost all (90%)
      commercial sex partners suggested condom use and provided condoms compared with
      8.1% of non-sex worker partners. Condom use showed a negative association with
      inconvenience in its use among male respondents but not female respondents.
      CONCLUSION: STI prevention programs for adolescents must promote condom use with
      nonpaying partners, address barriers to condom use, and develop condom
      application skills, taking into account gender differences. Future research
      should explore condom use within dating relationships.

PMID- 23000348
TI  - Adhesive capsulitis of the hip: a case report: an entity in question.
AB  - Very little has been discussed in the medical literature concerning adhesive
      capsulitis of the hip (ACH). There are no articles to date in the physical
      therapy literature regarding ACH and only a dozen or so in medical journals.
      Evidence suggests ACH may present in a similar progression through four stages as
      adhesive capsulitis of the shoulder (ACS) (from synovial inflammation to capsular
      fibrosis). Consensus does not exist for management of ACS or ACH. However, most
      clinicians agree that treatment should be guided by the stage of the disorder,
      whether medically, surgically, or through physical therapy. A large part of the
      confusion for management of adhesive capsulitis (ACS and ACH) is due to the many
      studies that have not reported their findings by stage. Arthroscopy and
      synovial/capsular biopsy can confirm the presence and stage of adhesive
      capsulitis. Primary (idiopathic) ACH is proposed to be caused by biomechanical
      dysfunction in the hip or other joints related to the mechanical function of the
      hip. The treatment for stages 1 and 2 consists of using techniques to reduce
      inflammation and correct biomechanical faults that affect the hip. In stages 3
      and 4 treatment focuses on the biomechanical dysfunction of the spine, hip(s),
      pelvic ring, and lower limb, if needed. In this case, the 55-year-old female
      patient presenting with probable stage 3 adhesive capsulitis, responded well to
      manual therapy and has been able to return to functional activities and maintain
      them with a home program. 

PMID- 23000349
TI  - Effects of okadaic acid on haemocytes from Mytilus galloprovincialis: a
      comparison between field and laboratory studies.
AB  - Individuals of Mytilus galloprovincialis, contaminated with Diarrheic Shellfish
      Poisoning (DSP) toxins, were studied with the aim to correlate the okadaic acid
      (OA) body burden and the percentage of damaged haemocytes by quantifying annexin
      V positive cells by flow cytometry. Results showed less percentage of damaged
      haemocytes in high OA contaminated samples. These data were compared with results
      of in vitro assays of mussel haemocytes exposed to increased concentrations of
      OA. Similarly, haemocytes exposed to the most concentrated OA solution were less
      damaged.

PMID- 23000350
TI  - Multi walled carbon nano tubes induced hepatotoxicity in Swiss albino mice.
AB  - In the present study, multi walled carbon nano tubes (MWCNTs) were synthesized
      using chemical vapour deposition (CVD) technique. Swiss albino mice were orally
      administered with single dose of 60 and 100 mg/kg body weight of purified and
      functionalized MWCNTs suspended in water. The mice were autopsied on 7, 14, 21
      and 28 days post exposure. Liver was taken out and part of it fixed in Bouin's
      solution for histopathological examinations. The remaining part was immersed in
      cold saline, blotted dry, weighed quickly and homogenized in ice cold buffer. The
      activity of superoxide dismutase (SOD) and catalase (CAT) was immediately
      measured in the supernatant. The MWCNTs in liver led to pathological changes,
      including injury to macrophages, cellular swelling, unspecific inflammation, spot
      necrosis and blood coagulation. Estimation of SOD and CAT showed altered levels
      in the experimental groups as compared to controls. Therefore, MWCNTs from
      manufactured and combustion sources in the environment can have adverse effects
      on human health.

PMID- 23000351
TI  - New insights into pharmacological profile of LASSBio-579, a multi-target N
      phenylpiperazine derivative active on animal models of schizophrenia.
AB  - Previous behavioral and receptor binding studies on N-phenylpiperazine
      derivatives by our group indicated that LASSBio-579, LASSBio-580 and LASSBio-581
      could be potential antipsychotic lead compounds. The present study identified
      LASSBio-579 as the most promising among the three compounds, since it was the
      only one that inhibited apomorphine-induced climbing (5 mg/kg p.o.) and
      apomorphine-induced hypothermia (15 mg/kg p.o.). Furthermore, LASSBio-579 (0.5
      mg/kg p.o.) was effective in the ketamine-induced hyperlocomotion test and
      prevented the prepulse inhibition deficits induced by apomorphine, DOI and
      ketamine with different potencies (1 mg/kg, 0.5 mg/kg and 5 mg/kg p.o.,
      respectively). LASSBio-579 also induced a motor impairment, catalepsy and a mild
      sedative effect but only at doses 3-120 times higher than those with
      antipsychotic-like effects. In addition, LASSBio-579 (0.5 and 1 mg/kg p.o.)
      reversed the catalepsy induced by WAY 100,635, corroborating its action on both
      dopaminergic and serotonergic neurotransmission and pointing to the contribution
      of 5-HT(1A) receptor activation to its pharmacological profile. Moreover, co
      administration of sub-effective doses of LASSBio-579 with sub-effective doses of
      clozapine or haloperidol prevented the apomorphine-induced climbing without
      induction of catalepsy. In summary, our results characterize LASSBio-579 as a
      multi-target ligand active in pharmacological animal models of schizophrenia,
      confirming that this compound could be included in development programs aiming at
      a new drug for treating schizophrenia.

PMID- 23000352
TI  - Pheromone-induced odor learning modifies Fos expression in the newborn rabbit
      brain.
AB  - Associative learning contributes crucially to adjust the behavior of neonates to
      the permanently changing environment. In the European rabbit, the mammary
      pheromone (MP) excreted in milk triggers sucking behavior in newborns, and
      additionally promotes very rapid learning of initially neutral odor cues. Such
      stimuli become then as active as the MP itself to elicit the orocephalic motor
      responses involved in suckling. In this context, the rabbit is an interesting
      model to address the question of brain circuits early engaged by learning and
      memory. Here, we evaluated the brain activation (olfactory bulb and central
      regions) induced in 4-day-old pups by an odorant (ethyl acetoacetate, EAA) after
      single pairing with the MP and its subsequent acquired ability to elicit sucking
      related behavior (conditioned group) or after mere exposure to EAA alone
      (unconditioned group). The brain-wide mapping of c-Fos expression was used to
      compare neural activation patterns in both groups. Evidence of high
      immunostaining to odorant EAA occurred in the mitral+granule cells layer of the
      main olfactory bulb in pups previously exposed to EAA in association with the MP.
      These pups also showed higher expression of Fos in the piriform cortex, the
      hypothalamic lateral preoptic area and the amygdala (cortical and basal nuclei).
      Thus, MP-induced odor learning induces rapid brain modifications in rabbit
      neonates. The cerebral framework supporting the acquisition appears however
      different compared to the circuit involved in the processing of the MP itself.

PMID- 23000353
TI  - Darwinism, not mutationism, explains the design of organisms.
AB  - Shapiro claims that advances in molecular genetics have undermined Darwinism,
      leading him to advocate mutationism. However, this extreme view is bourne out of
      conceptual error. He has misunderstood the distinction between gradualism and
      saltationism, which do not concern the rate of genetic change, but rather the
      emergence of complex design. And he has misunderstood the relationship between
      the dynamics of natural selection and the agency of individual organisms: these
      are not competing hypotheses, but rather alternative conceptualizations of the
      same phenomenon.

PMID- 23000354
TI  - Measuring titratable alkalinity by single versus double endpoint titration: An
      evaluation in two cyprinodont species and implications for characterizing net H+
      flux in aquatic organisms.
AB  - In this study, Na(+) uptake and acid-base balance in the euryhaline pupfish
      Cyprinodon variegatus variegatus were characterized when fish were exposed to pH
      4.5 freshwater (7mM Na(+)). Similar to the related cyprinodont, Fundulus
      heteroclitus, Na(+) uptake was significantly inhibited when exposed to low pH
      water. However, it initially appeared that C. v. variegatus increased apparent
      net acid excretion at low pH relative to circumneutral pH. This result is
      opposite to previous observations for F. heteroclitus under similar conditions
      where fish were observed to switch from apparent net H(+) excretion at
      circumneutral pH to apparent net H(+) uptake at low pH. Further investigation
      revealed disparate observations between these studies were the result of using
      double endpoint titrations to measure titratable alkalinity fluxes in the current
      study, while the earlier study utilized single endpoint titrations to measure
      these fluxes (i.e.,. Cyprinodon acid-base transport is qualitatively similar to
      Fundulus when characterized using single endpoint titrations). This led to a
      comparative investigation of these two methods. We hypothesized that either the
      single endpoint methodology was being influenced by a change in the buffer
      capacity of the water (e.g., mucus being released by the fish) at low pH, or the
      double endpoint methodology was not properly accounting for ammonia flux by the
      fish. A series of follow-up experiments indicated that buffer capacity of the
      water did not change significantly, that excretion of protein (a surrogate for
      mucus) was actually reduced at low pH, and that the double endpoint methodology
      does not properly account for NH(3) excretion by fish under low pH conditions. As
      a result, it overestimates net H(+) excretion during low pH exposure. After
      applying the maximum possible correction for this error (i.e., assuming that all
      ammonia is excreted as NH(3)), the double endpoint methodology indicates that net
      H(+) transport was reduced to effectively zero in both species at pH 4.5.
      However, significant differences between the double endpoint (no net H(+)
      transport at low pH) and single endpoint titrations (net H(+) uptake at low pH)
      remain to be explained.

PMID- 23000355
TI  - Intestinal fatty acid binding protein (fabp2) in Atlantic salmon (Salmo salar):
      Localization and alteration of expression during development of diet induced
      enteritis.
AB  - In the present study full-length cDNAs corresponding to three isoforms of
      intestinal fatty acid binding protein (fabp2) in Atlantic salmon were cloned and
      characterized. Gene expression of fabp2 was observed in all tissues investigated,
      although differences were observed between isoforms. The highest fabp2a1,
      fabp2a2, and fabp2b expression was in the intestine. A 15kDa protein,
      corresponding to putative Fabp2 protein, was identified by immunoblotting using
      anti-human Fabp2 antibody. Immunoblotting and immunohistochemistry confirmed that
      Fabp2 protein was present in most Atlantic salmon tissues. Similar to gene
      expression, intestinal tissues had the highest Fabp2 protein levels, decreasing
      gradually from proximal to distal intestine. During development of distal
      intestinal inflammation caused by dietary soybean meal from 0 to 21days, Fabp2
      decreased significantly on both transcriptional and protein levels. The reduction
      in Fabp2 was preceded by a down regulation of peroxisome proliferator activated
      receptor (ppar) alpha and gamma, fabp2's presumed regulatory proteins, and
      followed by a progressive increase in proliferating cell nuclear antigen (Pcna)
      staining. Results illustrate that the early decline of distal intestinal fabp2
      was likely caused by a down regulation of their regulatory proteins, but at later
      time points reduced Fabp2 may largely be due to a less mature enterocyte
      population resulting from rapid cell turnover.

PMID- 23000356
TI  - PAR-1 antagonist SCH79797 ameliorates apoptosis following surgical brain injury
      through inhibition of ASK1-JNK in rats.
AB  - Neurosurgical procedures inevitably produce intraoperative hemorrhage. The
      subsequent entry of blood into the brain parenchyma results in the release of
      large amounts of thrombin, a known contributor to perihematomal edema formation
      and apoptosis after brain injury. The present study seeks to test 1) the effect
      of surgically induced brain injury (SBI) on thrombin activity, expression of
      thrombin's receptor PAR-1, and PAR-1 mediated apoptosis; 2) the effect of
      thrombin inhibition by argatroban and PAR-1 inhibition by SCH79797 on the
      development of secondary brain injury in the SBI model on rats. A total of 88
      Sprague-Dawley male rats were randomly divided into sham, vehicle-, argatroban-,
      or SCH79797-treated groups. SBI involved partial resection of the right frontal
      lobe under inhalation isoflurane anesthesia. Sham-operated animals received only
      craniotomy. Thrombin activity, brain water content, and neurological deficits
      were measured at 24 h following SBI. Involvement of the Ask1/JNK pathway in PAR-1
      induced post-SBI apoptosis was characterized by using Ask1 or JNK inhibitors. We
      observed that SBI increased thrombin activity, yet failed to demonstrate any
      effect on PAR-1 expression. Argatroban and SCH79797 reduced SBI-induced brain
      edema and neurological deficits in a dose-dependent manner. SBI-induced apoptosis
      seemed mediated by the PAR-1/Ask1/JNK pathways. Administration of SCH79797
      ameliorated the apoptosis following SBI. Our findings indicate that PAR-1
      antagonist protects against secondary brain injury after SBI by decreasing both
      brain edema and apoptosis by inactivating PAR-1/Ask1/JNK pathway. The anti
      apoptotic effect of PAR-1 antagonists may provide a promising path for therapy
      following SBI.

PMID- 23000359
TI  - Regulation of Drosophila mesoderm migration by phosphoinositides and the PH
      domain of the Rho GTP exchange factor Pebble.
AB  - The Drosophila RhoGEF Pebble (Pbl) is required for cytokinesis and migration of
      mesodermal cells. In a screen for genes that could suppress migration defects in
      pbl mutants we identified the phosphatidylinositol phosphate (PtdInsP) regulator
      pi5k59B. Genetic interaction tests with other PtdInsP regulators suggested that
      PtdIns(4,5)P2 levels are important for mesoderm migration when Pbl is depleted.
      Consistent with this, the leading front of migrating mesodermal cells was
      enriched for PtdIns(4,5)P2. Given that Pbl contains a Pleckstrin Homology (PH)
      domain, a known PtdInsP-binding motif, we examined PtdInsP-binding of Pbl and the
      importance of the PH domain for Pbl function. In vitro lipid blot assays showed
      that Pbl binds promiscuously to PtdInsPs, with binding strength associated with
      the degree of phosphorylation. Pbl was also able to bind lipid vesicles
      containing PtdIns(4,5)P2 but binding was strongly reduced upon deletion of the PH
      domain. Similarly, in vivo, loss of the PH domain prevented localisation of Pbl
      to the cell cortex and severely affected several aspects of early mesoderm
      development, including flattening of the invaginated tube onto the ectoderm,
      extension of protrusions, and dorsal migration to form a monolayer. Pbl lacking
      the PH domain could still localise to the cytokinetic furrow, however, and
      cytokinesis failure was reduced in pbl(DeltaPH) mutants. Taken together, our
      results support a model in which interaction of the PH-domain of Pbl with
      PtdIns(4,5)P2 helps localise it to the plasma membrane which is important for
      mesoderm migration.

PMID- 23000360
TI  - Sifting through the heterogeneity of the Rapid Response System literature.

PMID- 23000357
TI  - FGF signaling transforms non-neural ectoderm into neural crest.
AB  - The neural crest arises at the border between the neural plate and the adjacent
      non-neural ectoderm. It has been suggested that both neural and non-neural
      ectoderm can contribute to the neural crest. Several studies have examined the
      molecular mechanisms that regulate neural crest induction in neuralized tissues
      or the neural plate border. Here, using the chick as a model system, we address
      the molecular mechanisms by which non-neural ectoderm generates neural crest. We
      report that in response to FGF the non-neural ectoderm can ectopically express
      several early neural crest markers (Pax7, Msx1, Dlx5, Sox9, FoxD3, Snail2, and
      Sox10). Importantly this response to FGF signaling can occur without inducing
      ectopic mesodermal tissues. Furthermore, the non-neural ectoderm responds to FGF
      by expressing the prospective neural marker Sox3, but it does not express
      definitive markers of neural or anterior neural (Sox2 and Otx2) tissues. These
      results suggest that the non-neural ectoderm can launch the neural crest program
      in the absence of mesoderm, without acquiring definitive neural character.
      Finally, we report that prior to the upregulation of these neural crest markers,
      the non-neural ectoderm upregulates both BMP and Wnt molecules in response to
      FGF. Our results provide the first effort to understand the molecular events
      leading to neural crest development via the non-neural ectoderm in amniotes and
      present a distinct response to FGF signaling.

PMID- 23000358
TI  - Sprouty/FGF signaling regulates the proximal-distal feather morphology and the
      size of dermal papillae.
AB  - In a feather, there are distinct morphologies along the proximal-distal axis. The
      proximal part is a cylindrical stalk (calamus), whereas the distal part has barb
      and barbule branches. Here we focus on what molecular signaling activity can
      modulate feather stem cells to generate these distinct morphologies. We
      demonstrate the drastic tissue remodeling during feather cycling which includes
      initiation, growth and resting phases. In the growth phase, epithelial components
      undergo progressive changes from the collar growth zone to the ramogenic zone, to
      maturing barb branches along the proximal-distal axis. Mesenchymal components
      also undergo progressive changes from the dermal papilla, to the collar
      mesenchyme, to the pulp along the proximal-distal axis. Over-expression of Spry4,
      a negative regulator of receptor tyrosine kinases, promotes barb branch formation
      at the expense of the epidermal collar. It even induces barb branches from the
      follicle sheath (equivalent to the outer root sheath in hair follicles). The
      results are feathers with expanded feather vane regions and small or missing
      proximal feather shafts (the calamus). Spry4 also expands the pulp region while
      reducing the size of dermal papillae, leading to a failure to regenerate. In
      contrast, over-expressing Fgf10 increases the size of the dermal papillae,
      expands collar epithelia and mesenchyme, but also prevents feather branch
      formation and feather keratin differentiation. These results suggest that
      coordinated Sprouty/FGF pathway activity at different stages is important to
      modulate feather epidermal stem cells to form distinct feather morphologies along
      the proximal-distal feather axis.

PMID- 23000361
TI  - Emergency department inter-hospital transfer for post-cardiac arrest care:
      initial experience with implementation of a regional cardiac resuscitation center
      in the United States.
AB  - OBJECTIVE: The American Heart Association recently recommended regional cardiac
      resuscitation centers (CRCs) for post-resuscitation care following out-of
      hospital cardiac arrest (OHCA). Our objective was to describe initial experience
      with CRC implementation. METHODS: Prospective observational study of consecutive
      post-resuscitation patients transferred from community Emergency Departments
      (EDs) to a CRC over 9 months. Transfer criteria were: OHCA, return of spontaneous
      circulation (ROSC), and comatose after ROSC. Incoming patients were received and
      stabilized in the ED of the CRC where advanced therapeutic hypothermia (TH)
      modalities were applied. Standardized post-resuscitation care included: ED
      evaluation for cardiac catheterization, TH (33-34  degrees C) for 24h, 24h/day
      critical care physician support, and evidence-based neurological prognostication.
      Prospective data collection utilized the Utstein template. The primary outcome
      was survival to hospital discharge with good neurological function [Cerebral
      Performance Category 1 or 2]. RESULTS: Twenty-seven patients transferred from 11
      different hospitals were included. The majority (21/27 [78%]) had arrest
      characteristics suggesting poor prognosis for survival (i.e. asystole/pulseless
      electrical activity initial rhythm, absence of bystander cardiopulmonary
      resuscitation, or an unwitnessed cardiac arrest). The median (IQR) time from
      transfer initiation to reaching TH target temperature was 7(5-13)h. Ten (37%)
      patients survived to hospital discharge, and of these 9/10 (90% of survivors, 33%
      of all patients) had good neurological function. CONCLUSIONS: Despite a high
      proportion of patients with cardiac arrest characteristics suggesting poor
      prognosis for survival, we found that one-third of CRC transfers survived with
      good neurological function. Further research to determine if regional CRCs
      improve outcomes after cardiac arrest is warranted.

PMID- 23000362
TI  - Clinical examination gloves - fit only for their intended purpose.

PMID- 23000363
TI  - The influence of induced hypothermia and delayed prognostication on the mode of
      death after cardiac arrest.
AB  - BACKGROUND: Brain injury is considered the main cause of death in patients who
      are hospitalized after cardiac arrest (CA). Induced hypothermia is recommended as
      neuroprotective treatment after (CA) but may affect prognostic parameters. We
      evaluated the effect of delayed neurological prognostication on the mode of death
      in hypothermia-treated CA-survivors. STUDY DESIGN: Retrospective study at a
      Swedish university hospital, analyzing all in-hospital and out-of-hospital CA
      patients treated with hypothermia during a 5-year period. Cause of death was
      categorized as brain injury, cardiac disorder or other. Multimodal neurological
      prognostication and decision on level of care was performed in comatose patients
      72 h after rewarming. Neurological function was evaluated by Cerebral Performance
      Categories scale (CPC). RESULTS: Among 162 patients, 76 survived to hospital
      discharge, 65 of whom had a good neurological outcome (CPC 1-2), and 11 were
      severely disabled (CPC 3). No patient was in vegetative state. The cause of death
      was classified as brain injury in 61 patients, cardiac disorder in 14 and other
      in 11. Four patients were declared brain dead and became organ donors. They were
      significantly younger (median 40 years) and with long time to ROSC. Active
      intensive care was withdrawn in 50 patients based on a statement of poor
      neurological prognosis at least 72 h after rewarming. These patients died, mainly
      from respiratory complications, at a median 7 days after CA. CONCLUSION:
      Following induced hypothermia and delayed neurological prognostication, brain
      injury remains the main cause of death after CA. Most patients with a poor
      prognosis statement died within 2 weeks.

PMID- 23000364
TI  - Retrospective evaluation of current-based impedance compensation defibrillation
      in out-of-hospital cardiac arrest.
AB  - OBJECTIVE: Transthoracic impedance (TTI) is a principal parameter that influences
      the intracardiac current flow and defibrillation outcome. In this study, we
      retrospectively evaluated the performance of current-based impedance compensation
      defibrillation in out-of-hospital cardiac arrest (OHCA) patients. METHODS: ECG
      recordings, along with TTI measurements were collected from multiple emergency
      medical services (EMSs) in the USA. All the EMSs in this study used automated
      external defibrillators (AEDs) which employing rectilinear biphasic (RLB)
      waveform. The distribution and change of TTI between successive shocks, the
      influence of preceding shock results on the subsequent shock outcome, and the
      performance of current-based impedance compensation defibrillation was evaluated.
      RESULTS: A total of 1166 shocks from 594 OHCA victims were examined in this
      study. The average TTI for the 1st shock was 134.8 Omega and a significant
      decrease in TTI was observed for the 2nd (p<0.001) and 3rd (p=0.033) sequential
      escalating shock. But TTI did not change after the 3rd shock. A higher success
      rate was observed for shocks with preceding defibrillation success. The success
      rate remained unchanged over the whole spectrum of TTI. CONCLUSION: The average
      TTI was relatively higher in this OHCA population treated with RLB defibrillation
      as compared with previously reported data. TTI was significantly decreased after
      1st and 2nd successive escalating shock but kept constant after the 3rd shock.
      Preceding shock success was a better predictor of subsequent defibrillation
      outcome other than TTI. Current-based impedance compensation defibrillation
      resulted in equivalent success rate for high impedance patients when compared
      with those of low impedance.

PMID- 23000365
TI  - Outcomes of patients with trauma and intraoperative cardiac arrest.
AB  - BACKGROUND: Although the occurrence of intraoperative cardiac arrest is rare, it
      is a severe adverse event with a high mortality rate. Trauma patients have
      additional causes for intraoperative arrest, and we hypothesised that the
      survival of trauma patients who experienced intraoperative cardiac arrest would
      be worse than nontrauma patients who experienced intraoperative cardiac arrest.
      OBJECTIVES: The aim of the present study was to compare the outcomes of trauma
      and nontrauma patients after intraoperative cardiac arrest. METHODS: In a
      tertiary university hospital and trauma centre, the intraoperative cardiac arrest
      cases were evaluated from January 2007 to December 2009, excluding patients
      submitted to cardiac surgery. Data were prospectively collected using the Utstein
      style. Outcomes among the patients with trauma were compared to the patients
      without trauma. RESULTS: We collected data from 81 consecutive intraoperative
      cardiac arrest cases: 32 with trauma and 49 without trauma. Patients in the
      trauma group were younger than the patients in the nontrauma group (44+/-23 vs.
      63+/-17, p<0.001). Hypovolaemia (63% vs. 35%, p=0.022) and
      metabolic/hydroelectrolytic disturbances (41% vs. 2%, p<0.001) were more likely
      to cause the cardiac arrest in the trauma group. The first documented arrest
      rhythm did not differ between the groups, and pulseless electrical activity was
      the most prevalent rhythm (66% vs. 53%, p=0.698). The return of spontaneous
      circulation (47% vs. 63%, p=0.146) and survival to discharge with favourable
      neurological outcome (16% vs. 14%, p=0.869) did not differ between the two
      groups. CONCLUSIONS: The outcomes did not differ between patients with trauma and
      nontrauma intraoperative cardiac arrest.

PMID- 23000366
TI  - [Controversies in neuroanaesthesia: positioning in neurosurgery].
AB  - Positioning of the neurosurgical patient has several features such as the
      existence of specific positions (i.e: sitting, prone hyperlordotic, crouching ou
      kneeling positions) or the range of facilities for the same surgical indications.
      The last point, a source of controversy, is the subject of this review. Current
      indications for the sitting position, positioning for lumbar spine surgery and
      prevention of eye injuries are successively addressed.

PMID- 23000367
TI  - Stearoyl-CoA desaturase: rogue or innocent bystander?
AB  - Different lipid fractions in humans have characteristic fatty acid profiles and
      these are maintained partly through diet and to a lesser extent through
      endogenous synthesis. The enzyme stearoyl-CoA desaturase (SCD; EC 1.14.99.5) is
      the rate-limiting enzyme in the synthesis of monounsaturated fatty acids such as
      palmitoleic acid (16:1 n-7) and oleic acid (18:1 n-9). These are the two most
      abundant monounsaturated fatty acids in human plasma lipids, membranes and
      adipose tissue. Although in quantitative terms, the endogenous synthesis of fatty
      acids in humans is not great in most circumstances, it is becoming increasingly
      evident that SCD plays important structural and metabolic roles. In addition,
      16:1 n-7 has been purported to act as a beneficial 'lipokine' in an animal model.
      Research in humans has relied on indirect measurements of SCD1 activity and
      therefore, much of our understanding has come from work on animal models.
      However, results have been somewhat counterintuitive and confusing, so the
      purpose of this review is to try to summarise our current understanding of this
      fascinating enzyme.

PMID- 23000368
TI  - Early improvement of psychotic symptoms with lithium monotherapy as a predictor
      of later response in mania.
AB  - Although lithium has been the first line agent in the treatment of bipolar
      disorder (BD), few studies have evaluated lithium's efficacy in mania with
      psychosis and its association with later response. Furthermore, given the
      widespread concern about antipsychotic side effects, answering a question about
      whether lithium alone can manage to treat both psychotic and non-psychotic mania
      seems a very relevant one. The present study addresses the antipsychotic efficacy
      of lithium monotherapy in acute mania and early improvement of psychotic symptoms
      as a predictor of later response of manic symptoms. Forty-six patients presenting
      a manic episode (32 with psychotic features and 14 subjects without psychotic
      features) were treated for 4 weeks with lithium monotherapy and evaluated weekly
      using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance
      abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy
      of lithium in psychosis vs. non-psychosis groups was evaluated. In addition,
      early improvement of psychotic symptoms and its prediction of subsequent response
      (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed
      a similar efficacy in both psychosis and non-psychosis mania. Early improvement
      of psychotic symptoms was associated with clinical response and remission at
      endpoint.

PMID- 23000369
TI  - NMR resolved multiple anesthetic binding sites in the TM domains of the
      alpha4beta2 nAChR.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) has significant roles in
      nervous system function and disease. It is also a molecular target of general
      anesthetics. Anesthetics inhibit the alpha4beta2 nAChR at clinically relevant
      concentrations, but their binding sites in alpha4beta2 remain unclear. The
      recently determined NMR structures of the alpha4beta2 nAChR transmembrane (TM)
      domains provide valuable frameworks for identifying the binding sites. In this
      study, we performed solution NMR experiments on the alpha4beta2 TM domains in the
      absence and presence of halothane and ketamine. Both anesthetics were found in an
      intra-subunit cavity near the extracellular end of the beta2 transmembrane
      helices, homologous to a common anesthetic binding site observed in X-ray
      structures of anesthetic-bound GLIC (Nury et al., [32]). Halothane, but not
      ketamine, was also found in cavities adjacent to the common anesthetic site at
      the interface of alpha4 and beta2. In addition, both anesthetics bound to
      cavities near the ion selectivity filter at the intracellular end of the TM
      domains. Anesthetic binding induced profound changes in protein conformational
      exchanges. A number of residues, close to or remote from the binding sites,
      showed resonance signal splitting from single to double peaks, signifying that
      anesthetics decreased conformation exchange rates. It was also evident that
      anesthetics shifted population of two conformations. Altogether, the study
      comprehensively resolved anesthetic binding sites in the alpha4beta2 nAChR.
      Furthermore, the study provided compelling experimental evidence of anesthetic
      induced changes in protein dynamics, especially near regions of the hydrophobic
      gate and ion selectivity filter that directly regulate channel functions.

PMID- 23000370
TI  - High prevalence of both anti-insulin and anti-insulin receptor antibodies in
      Korean patients with insulin autoimmune syndrome.
AB  - We performed a retrospective pooled analysis of 28 patients who had been
      diagnosed with insulin autoimmune syndrome and evaluated the prevalence of anti
      insulin receptor antibodies. Dual positivity for anti-insulin and anti-insulin
      receptor antibodies was common (53.8%). However, these patients had a similar
      phenotype compared with insulin receptor antibody-negative patients.

PMID- 23000371
TI  - Measurement of elasticity and transepidermal water loss rate of burn scars with
      the Dermalab((r)).
AB  - This cross-sectional study investigated the reproducibility of repeated
      elasticity and transepidermal water loss (TEWL) measurements with the
      DermaLab((r)) on 32 active burn scars and healthy skin. Intra- and inter-observer
      reproducibility was examined by means of intra-class correlation coefficients
      (ICC) and standard error of measurements (SEM). Results showed good ICC values
      and rather high SEM values for inter- and intra-observer reproducibility of
      elasticity measurements. For TEWL measurements, ICC values were good and SEM
      values were high for inter- and intra-observer reproducibility. There was a
      significant difference between the estimated mean elasticity values of normal
      skin and grafted scars and between normal skin and spontaneously healed scars
      (p<=0.003). For the estimated mean TEWL values, there was a significant
      difference between normal skin and spontaneously healed scars (p=0.036). A
      significant negative relation was reported between mean TEWL and time after burn
      (p=0.008). In clinical trials it is necessary to interpret patient-specific
      changes in elasticity and TEWL with caution, since the SEMs of both modes are
      rather high. We therefore recommend the use of a mean of repeated measurements of
      elasticity and TEWL to decrease the SEM.

PMID- 23000372
TI  - Flow-through anterolateral thigh flap for reconstruction in electrical burns of
      the severely damaged upper extremity.
AB  - BACKGROUND: Many surgeons have to face the challenge of the sophisticated
      management of catastrophic high-voltage injuries to upper extremities. These
      patients present with both vast soft tissue defects and varied segmental main
      artery defects with compromised circulation of the distal limb. This study is a
      first attempt to analyze the outcome of the flow-through anterolateral thigh flap
      for reconstruction in acute electrical burns of the severely traumatized upper
      extremity. METHOD AND PATIENT: From March 2001 to February 2012, five men were
      enrolled in the study. All in this series suffered from high voltage current
      (higher than 1000 V) electrical burn and had the presence of wide segmental soft
      tissue defects, exposure of underlying vital structures and segmental artery
      injury with compromised circulation. Flow-through anterolateral thigh flaps were
      used for limb salvage. RESULT: Follow up for all patients was present from 6
      months to 7 years. The mean age was 37.8 years old. The mean timing of free flap
      transfer was 5.8 days after injury. The mean flap sizes were 31.6 cm * 16.5 cm.
      The mean artery defect was 14.2 cm in length. Venous thrombosis occurred 1 day
      post-operatively in one patient. No donor site morbidity was noted. In the
      postoperative period, no infection, no hematoma, nor deaths were noted.
      Successful limb salvage rate was 80% in this series. CONCLUSION: In electrical
      injuries of the severely damaged upper extremity, flow through anterolateral
      thigh flaps provide for reconstruction of both the vessels and soft tissue
      simultaneously. Although the risk of flap failure is higher than with other
      etiologies of burn, the data shows that the above reconstruction technique is
      useful for upper extremity salvage.

PMID- 23000373
TI  - Serum immunoglobulin levels in pediatric burn patients.
AB  - Infections remain the leading cause of death in burn patients. Immune responses
      play an important role in patient's defense mechanism against infection and
      decreasing morbidity and mortality associated with burn. Our goal was to
      determine serum immunoglobulin levels in pediatric burn patients in order to
      understand role of humoral immune defense in these patients. During this analytic
      cross sectional study from January 2011 to February 2012, all patients with burn
      and younger than 6 years old that were referred to Shahid Motahari burn and
      reconstruction center were enrolled. Patients had no inhalation injury or sepsis.
      Immunoglobulin levels were measured once on 3-5 days after burn. The burn size in
      12 patients (24%) was less than 30%, in 30 patients (60%) were between 30% and
      50% and in the remained 8 patients (16%) were more than 50%. In 45 patients (90%)
      depth and severity of burn were 2nd degree (superficial and deep) and in the
      remaining 5 patients (10%), it was 3rd or 4th degree. In 28 (56%), 1 (2%), 3
      (6%), 35 (70%), 48 (96%), 19 (38%) and 6 (12%) patients IgG, IgM, IgA, IgG1,
      IgG2, IgG3 and IgG4 were lower than normal values, respectively. No significant
      correlation was seen between burn size (TBSA) and value of immunoglobulin
      (P>0.05). Although the drop in the serum concentration of immunoglobulins is
      irrespective to the burn size, more severe burn is associated with more decrease
      in the serum levels of IgA, IgM, IgG and its subclasses. However, further studies
      are needed to provide complementary data on this issue.

PMID- 23000374
TI  - Routine use of urinary hCG test in adult burn females to detect "hidden"
      pregnancies: a review.
AB  - Burns occurring in conjunction with pregnancy can be a potentially life
      threatening scenario as it may lead to a rapid depletion of the already
      diminished maternal reserves. The management protocol in a pregnant burn female
      has to be tailored, taking into consideration the additional factor of fetal well
      being and the fetal susceptibility to various agents. For such alterations to be
      incorporated, it is imperative on part of the treating doctor to correctly
      ascertain the pregnant/non-pregnant status of an adult burn female. Though most
      cases of pregnancy can be straightforwardly diagnosed on basis of
      history/examination but it is not a totally reliant method. Ours is a prospective
      study which reveals the inadequacy of history/examination as the only method of
      diagnosing pregnancy in adult burnt female group. We also found routine urinary
      hCG usage as a viable method of picking up these "hidden" cases of pregnancy and
      thus avert the potential catastrophe of not altering the management in accordance
      with pregnancy and subsequent endangering of maternal and fetal life. An
      ancillary observation of our study was the need of the attending doctor to be
      well versed in his obstetrical knowledge and skills and if not so, then an effort
      be taken on part of the institution to undertake a reorientation program which
      will help the attending resident/doctor to brush up his obstetrical attainments.

PMID- 23000375
TI  - Identification and characterization of a human IL-10 receptor antagonist.
AB  - Interleukin-10 (IL-10) is an anti-inflammatory cytokine that works through IL-10
      receptor alpha subunit- and suppresses immune responses in many infectious
      diseases such as leishmaniasis as well as in cancer. Therefore, in order to
      restore the host-protective immune responses in such diseases, an antagonist to
      this cytokine is a pressing need. Herein, using phage peptide library display, we
      have identified a dodecameric peptide that functions as an antagonist to human IL
      10 receptor in an IL-10-induced STAT3 phosphorylation assay. The peptide
      antagonist's ability to restore anti-leishmanial function in CD40-activated
      macrophages was also tested. We observed that the peptide reduced IL-10-induced
      STAT-3 phosphorylation and enhanced CD40-activated leishmanial functions in
      macrophages.

PMID- 23000376
TI  - No evidence of association between MBL2A/O polymorphisms and Mycobacterium
      tuberculosis infection in populations from the Brazilian Amazon region.
AB  - The present study investigated the prevalence of the polymorphisms in the exon 1
      of the MBL2 gene in patients with tuberculosis at a hospital in northern Brazil,
      which is a regional reference for the treatment of the disease. The study group
      was composed of 167 patients with tuberculosis, 34 of which had the extra
      pulmonary form of the disease, while the other 133 had the pulmonary type. The
      control group consists of 159 healthy individuals. Samples of DNA extracted from
      leucocytes were submitted to Polymerase Chain Reaction for the amplification of a
      120-bp segment of exon 1 of the MBL2 gene. The distribution of allele and
      genotype frequencies varied little among the different groups, and it was not
      possible to establish any clear association between the variants of the MBL2 gene
      and the susceptibility to or clinical profile of tuberculosis infections in the
      population analyzed.

PMID- 23000377
TI  - Low producer MBL genotypes are associated with susceptibility to systemic lupus
      erythematosus in Odisha, India.
AB  - Variants of MBL gene have been associated with autoimmune disorders. The aim of
      this study was to explore whether common polymorphisms in MBL gene are associated
      with susceptibility to systemic lupus erythematosus (SLE) and its clinical
      manifestations in a cohort from eastern India. A total of 108 female SLE patients
      and 105 age, sex, and ethnically matched healthy controls were enrolled in the
      study. MBL2 codon and promoter polymorphisms were genotyped by AS-PCR and dARMS
      PCR, respectively. Plasma level of MBL was quantified by ELISA. Higher frequency
      of BB genotype and minor allele (B) was observed in patients of SLE compared to
      healthy controls (BB genotype: P = 0.0002; OR = 5.75, 95% CI = 2.09-15.76, B
      allele: P < 0.0001; OR = 2.78, 95% CI = 1.66-4.64). MBL codon 54, H-550L, Y-221X
      polymorphisms and combined MBL genotypes contributed to plasma MBL levels.
      Prevalence of MBL low producer genotype (LXA/LYB, LYB/LYB and LXB/LXB) was
      significantly higher in SLE patients compared to healthy control. (P = 0.005; OR
      = 3.09, 95% CI = 1.38-6.91). On analysis of clinical manifestations, MBL low
      producer genotype was significantly associated with autoimmune haemolytic anaemia
      (P = 0.006; OR = 13.06). Results of the present study indicate MBL2 variants as
      possible risk factors for development of SLE and clinical manifestation in
      eastern India.

PMID- 23000378
TI  - The fusion Vibrio campbellii luciferase as a eukaryotic gene reporter.
AB  - Bacterial luciferase from Vibrio campbellii is a thermostable enzyme with an in
      vitro thermal inactivation half-life of ~1020 min at 37 degrees C. The enzyme
      also binds tightly to reduced FMN. In this study, a V. campbellii fusion
      luciferase construct in which the alpha and beta subunits are linked with a
      decapeptide was made and characterized. In general, the overall enzymatic
      properties of the two enzymes are similar. Expression of the enzymes in
      Escherichia coli demonstrated that the V. campbellii fusion luciferase emits less
      light than the native luciferase, but still emits a much greater amount of light
      than native luciferase from Vibrio harveyi and Photobacterium leiognathi TH1. The
      intensity of light emitted by the V. campbellii fusion luciferase was more than
      80-fold greater than that from the V. harveyi native luciferase when expressed at
      37 degrees C. Biochemical characterization has shown that the V. campbellii
      fusion luciferase also retains a high binding affinity for reduced flavin
      mononucleotide and high thermostability. The levels of bioluminescence emitted by
      the V. campbellii fusion luciferase expressed in HEK293T cells reached ~1*10(6)
      Relative Light Units/mg total protein. These findings suggest that the V.
      campbellii fusion luciferase is a promising candidate for further development as
      a luciferase-based reporter for eukaryotic systems.

PMID- 23000379
TI  - Gallstone abscess as a result of dropped gallstones during laparoscopic
      cholecystectomy.
AB  - INTRODUCTION: With the advent of laparoscopic cholecystectomy we have seen a
      "disease of medical progress" (DOMP). Herein we report a complication that
      developed 7 years after laparoscopic cholecystectomy. PRESENTATION OF CASE: A 42
      year old woman presented with worsening right-sided pain and tenderness. Seven
      years prior she underwent a laparoscopic cholecystectomy. Computed tomography
      demonstrated a subhepatic retroperitoneal inflammatory mass. On open exploration
      a 4cm*6cm retroperitoneal mass was excised. The mass contained purulent material
      and gallstones. DISCUSSION: Laparoscopic cholecystectomy has become the "gold
      standard" for the treatment of symptomatic gallstones. Prior to laparoscopic
      cholecystectomy there was no body of literature about lost gallstones thus making
      this a DOMP. In contrast, it is reported that as many as 5.4-19% of laparoscopic
      cholecystectomies have stones spilled with variable rates of retrieval. Our case
      demonstrates an extreme example of a complication resulting seven years after a
      laparoscopic cholecystectomy with gallstones left behind. CONCLUSION: Recognizing
      that gallstones will be lost during some cases of laparoscopic cholecystectomy,
      we must remain vigilant and make a full attempt to retrieve all stones to prevent
      such rare but not insignificant potential complications.

PMID- 23000380
TI  - Stabilization of polyplexes via polymer crosslinking for efficient siRNA
      delivery.
AB  - The pseudodendritic, biodegradable polymer HD-O, consisting of an OEI800 core
      with several OEI800 molecules attached to it via 1.6-hexanediol diacrylate
      linkers, has potent pDNA but poor siRNA delivery ability, due to instability of
      the resulting siRNA polyplexes. Stabilization of such nanoparticles by
      crosslinking surface amines of HD-O in the polyplexes with dithiobis
      (succinimidylpropionate) (DSP) greatly enhanced gene silencing efficiency.
      Successful crosslinking on the polyplex surface was indicated by a decrease of
      the positive Zeta potential of the polyplexes. Tuning the polymer/siRNA ratio in
      combination with adjustment of the linker to a molar ratio of 0.05/1 between
      linker and polymer amines proved essential for transfection efficiency and
      prevention of particle aggregation. Gene silencing ability of the crosslinked
      particles was demonstrated in murine neuroblastoma N2A and human hepatoma HUH-7
      cells. Flow cytometry showed efficient cellular uptake already after 1h
      incubation with the crosslinked but not with unstabilized particles.
      Downregulation of endogenous AHA1 mRNA (85% knockdown compared to control) by
      crosslinked HD-O/AHA1-siRNA particles was detected by quantitative real-time PCR.

PMID- 23000381
TI  - Time-resolved near-infrared spectroscopic study of the dissolution of crystalline
      lactose.
AB  - In the present study, initial dissolution of crystalline alpha-lactose
      monohydrate was investigated via time-resolved Fourier Transform near-infrared
      (FT-NIR) spectroscopy using the liquid penetration method. The process of water
      penetration is classically characterized by a two-step increment in the
      combination bands between OH stretching and bending modes of water; however, only
      one-step increment in the combination bands was induced by penetration of lactose
      saturated solution. These results suggest that a first phase occurs in which
      penetrating water adsorbs to solid lactose surface creating a saturated layer,
      followed by a second phase of dissolution of the hydrated lactose. Decomposition
      of differential spectra at 2-min intervals supports the existence of an
      adsorption-diffusion model and gives a threshold as the amount of adsorbed water
      to dissolve solid lactose.

PMID- 23000382
TI  - Crystal structure of the yeast vacuolar ATPase heterotrimeric EGC(head)
      peripheral stalk complex.
AB  - Vacuolar ATPases (V-ATPases) are multisubunit rotary motor proton pumps that
      function to acidify subcellular organelles in all eukaryotic organisms. V-ATPase
      is regulated by a unique mechanism that involves reversible dissociation into V1
      ATPase and V0 proton channel, a process that involves breaking of protein
      interactions mediated by subunit C, the cytoplasmic domain of subunit "a" and
      three "peripheral stalks," each made of a heterodimer of E and G subunits. Here,
      we present crystal structures of a yeast V-ATPase heterotrimeric complex composed
      of EG heterodimer and the head domain of subunit C (C(head)). The structures show
      EG heterodimer folded in a noncanonical coiled coil that is stabilized at its N
      terminal ends by binding to C(head). The coiled coil is disrupted by a bulge of
      partially unfolded secondary structure in subunit G and we speculate that this
      unique feature in the eukaryotic V-ATPase peripheral stalk may play an important
      role in enzyme structure and regulation by reversible dissociation.

PMID- 23000383
TI  - The structure of the plk4 cryptic polo box reveals two tandem polo boxes required
      for centriole duplication.
AB  - Centrioles are key microtubule polarity determinants. Centriole duplication is
      tightly controlled to prevent cells from developing multipolar spindles, a
      situation that promotes chromosomal instability. A conserved component in the
      duplication pathway is Plk4, a polo kinase family member that localizes to
      centrioles in M/G1. To limit centriole duplication, Plk4 levels are controlled
      through trans-autophosphorylation that primes ubiquitination. In contrast to Plks
      1-3, Plk4 possesses a unique central region called the "cryptic polo box." Here,
      we present the crystal structure of this region at 2.3 A resolution.
      Surprisingly, the structure reveals two tandem homodimerized polo boxes, PB1-PB2,
      that form a unique winged architecture. The full PB1-PB2 cassette is required for
      binding the centriolar protein Asterless as well as robust centriole targeting.
      Thus, with its C-terminal polo box (PB3), Plk4 has a triple polo box architecture
      that facilitates oligomerization, targeting, and promotes trans
      autophosphorylation, limiting centriole duplication to once per cell cycle.

PMID- 23000384
TI  - Solution conformations of prototype foamy virus integrase and its stable synaptic
      complex with U5 viral DNA.
AB  - Using small-angle X-ray and neutron scattering (SAXS/SANS), in combination with
      analytical centrifugation and light scattering, we have determined the solution
      properties of PFV IN alone and its synaptic complex with processed U5 viral DNA
      and related these properties to models derived from available crystal structures.
      PFV IN is a monomer in solution, and SAXS analysis indicates an ensemble of
      conformations that differ from that observed in the crystallographic DNA-bound
      state. Scattering data indicate that the PFV intasome adopts a shape in solution
      that is consistent with the tetrameric assembly inferred from crystallographic
      symmetry, and these properties are largely preserved in the presence of divalent
      ions and clinical strand transfer inhibitors. Using contrast variation methods,
      we have reconstructed the solution structure of the PFV intasome complex and have
      located the distal domains of IN that were unresolved by crystallography. These
      results provide important insights into the architecture of the retroviral
      intasome.

PMID- 23000385
TI  - Proton-coupled dynamics in lactose permease.
AB  - Lactose permease of Escherichia coli (LacY) catalyzes symport of a
      galactopyranoside and an H+ via an alternating access mechanism. The transition
      from an inward- to an outward-facing conformation of LacY involves sugar-release
      followed by deprotonation. Because the transition depends intimately upon the
      dynamics of LacY in a bilayer environment, molecular dynamics (MD) simulations
      may be the only means of following the accompanying structural changes in atomic
      detail. Here, we describe MD simulations of wild-type apo LacY in
      phosphatidylethanolamine (POPE) lipids that features two protonation states of
      the critical Glu325. While the protonated system displays configurational
      stability, deprotonation of Glu325 causes significant structural rearrangements
      that bring into proximity side chains important for H+ translocation and sugar
      binding and closes the internal cavity. Moreover, protonated LacY in
      phosphatidylcholine (DMPC) lipids shows that the observed dynamics are lipid
      dependent. Together, the simulations describe early dynamics of the inward-to
      outward transition of LacY that agree well with experimental data.

PMID- 23000386
TI  - The use of pH-sensitive positively charged polymeric micelles for protein
      delivery.
AB  - In this investigation, a nano-sized protein-encapsulated polymeric micelle was
      prepared by self-assembling human serum albumin (HSA) as a model protein and
      degradable block copolymer methoxy poly(ethylene glycol)-poly(beta-amino ester)
      (PEG-PAE) with piperidine and imidazole rings. From the zeta potential
      measurement, the protein-encapsulated polymeric micelle showed a pH-tuning charge
      conversion from neutral to positive when pH decreases from 7.8 to 6.2. It was
      envisioned that the pH-tunable positively charged polymeric micelle could enhance
      the protein delivery efficiency and, simultaneously, target to the pH-stimuli
      tissue, such as cancerous tissue or ischemia. The pH-dependent particle size and
      scattering intensity were also measured and showed 50-70 nm particle size.
      Consequently, the circular dichroism (CD) spectroscopy confirmed that the
      secondary structure of albumin was unaffected during the pH changing process. The
      in vitro cytotoxicity for the polymeric micelle was evaluated on MDA-MB-435 cell
      lines and no obvious toxicity could be observed when the polymer concentration
      was below 200 MUg/mL. To assess the ability of this pH-tunable positively charged
      polymeric micelle as a vehicle for protein delivery to in vivo acidic tissues, we
      utilized a disease rat model of cerebral ischemia that produced an acidic tissue
      due to its pathologic condition. The rat was intravenously injected with the
      Cy5.5-labled albumin-encapsulated polymeric micelle. We found a gradual increase
      in fluorescence signals of the brain ischemic area, indicating that the pH-tuning
      positively charged protein-encapsulated polymeric micelle could be effective for
      targeting the acidic environment and diagnostic imaging.

PMID- 23000387
TI  - Serotonergic neuromodulation of peripheral nociceptors.
AB  - Nociception, the encoding and processing of noxious environmental stimuli by
      sensory neurons, functions to protect an organism from bodily damage. Activation
      of the terminal endings of certain sensory neurons, termed nociceptors, triggers
      a train of impulses to neurons in the spinal cord. Signals are integrated and
      processed in the dorsal spinal cord and then projected to the brain where they
      elicit the perception of pain. A number of neuromodulators that can affect
      nociceptors are released in the periphery during the inflammation that follows an
      initial injury. Serotonin (5-HT) is a one such proinflammatory mediator. This
      review discusses our current understanding of the neuromodulatory role of 5-HT,
      and specifically how this monoamine activates and sensitizes nociceptors.
      Potential therapeutic targets to treat pain are described.

PMID- 23000388
TI  - Histopathologic features of ovarian borderline tumors are not predictive of
      clinical outcome.
AB  - OBJECTIVES: Ovarian borderline tumors (BOTs) generally have an excellent
      prognosis, although recurrences and malignant transformation can occur. Our aim
      was to compare clinicopathologic features of BOT with clinical outcome. METHODS:
      In seventy consecutive BOTs clinicopathologic parameters, tumor cell
      proliferation (Ki67) and in selected cases KRAS, BRAF and p53 mutational status
      were analyzed with recurrence-free and overall survival as the endpoints.
      RESULTS: Sixty-one (87%) patients presented with FIGO stage I, 3 stage II, and 6
      stage III. Thirty-four patients had serous and 36 mucinous BOT (30 intestinal and
      6 endocervical subtypes). Non-invasive peritoneal implants occurred in 9
      patients, and no invasive implants were observed. Recurrence-free and overall
      survival rates were 91% and 99%, respectively, at a mean follow-up of 63 months.
      Disease recurrence occurred in 6 cases (all FIGO stage I) including 3 serous, 1
      mucinous-intestinal, and 2 mucinous-endocervical subtypes. Mean time to
      recurrence was 27 months (range 8-68). The recurrence rate following fertility
      conserving surgery was 31% (5/16) compared to 2% (1/54) after bilateral salpingo
      oophorectomy. Neither peritoneal implants (9/70), micropapillary pattern (2/34),
      microinvasion (4/70), nor increased tumor cell proliferation was associated with
      a higher recurrence rate. The frequency of KRAS or BRAF mutations was 50% (3/6
      recurrences and 3/6 controls; 4 KRAS, 2 BRAF mutations). No p53 mutations (0/12)
      were detected in primary or recurrent BOTs. CONCLUSIONS: Histopathologic
      parameters were not predictive of BOT recurrence including previously suggested
      risk factors such as micropapillary pattern and microinvasion. However, fertility
      conserving surgery and incomplete surgical staging were associated with a higher
      risk for recurrence.

PMID- 23000389
TI  - Cytokine use and survival in the first-line treatment of ovarian cancer: a
      Gynecologic Oncology Group Study.
AB  - BACKGROUND: Granulocyte colony stimulating factor (G-CSF) and erythropoietin
      stimulating agents (ESA) may be used to support patients during chemotherapy. We
      assessed whether G-CSF or ESA were associated with progression or death in
      patients with ovarian cancer. METHODS: Patients with ovarian cancer following
      surgery, were on a protocol to evaluate bevacizumab with chemotherapy. Guidelines
      for administering G-CSF and ESA were specified in the protocol. Overall survival
      (OS) was analyzed with landmark procedures and multivariate, time-dependent
      hazard models. RESULTS: Eighteen-hundred-seventy-three women were enrolled, with
      no differences in clinical and pathologic variables among treatment group.
      Performance status, hemoglobin, and white cell counts were associated with G-CSF
      and/or ESA usage during treatment. Nine patients received no protocol directed
      therapy, leaving 1864 patients for this review. One-thousand-one-hundred-twenty
      five patients received neither ESA nor G-CSF; 311 received G-CSF but no ESA; 241
      received ESA but no G-CSF; and 187 received both. Median survival following a
      five month landmark from the start of treatment was 34 versus 38 months for those
      who did versus did not receive ESA (multivariate hazard ratio: 0.989; 95%
      confidence interval: 0.849-1.15) and 40 versus 37 months for those who did versus
      did not receive G-CSF (multivariate hazard ratio: 0.932; 95% confidence interval:
      0.800-1.08). CONCLUSIONS: Neither ESA nor G-CSF had a negative impact on survival
      after adjustment of prognostic factors among patients with ovarian cancer
      receiving chemotherapy. ESA may appear to be associated with shorter survival in
      univariate analyses because factors prognostic for ESA use are also prognostic
      for progression-free survival.

PMID- 23000390
TI  - Pharmacology of ectonucleotidases: relevance for the treatment of cardiovascular
      disorders.
AB  - ATP and other extracellular nucleotides have diverse and potent effects in
      different organs. Evidence indicates that extracellular nucleotides and
      nucleosides deliver crucial signals by acting upon a wide variety of purinergic
      receptors, which include 19 members separated in three families. Purinergic
      receptors encompass adenosine-sensitive receptors (P1) as well as the ATP and ADP
      responsive receptors (P2). On the other side, P2 receptors are divided into
      ionotropic P2X receptors and G protein-coupled receptors P2Y. This system of
      purinergic signaling is made further complex by the fact that ectonucleotidases,
      membrane bound enzymes, participate in the metabolism of extracellular
      nucleotides, which are released by cells. Hence, ectonucleotidases are important
      modulators of purinergic receptor function. It should be pointed out that the
      ectonucleotidases includes enzymes with different substrate preferences and by
      their action generate different nucleotides and nucleosides as well as phosphate
      and pyrophosphate. A growing body of evidence points toward the fact that the
      expression pattern of different ectonucleotidases and purinergic receptors is
      implicated in several cardiovascular disorders. In this perspective, a short
      account is given on the role of ectonucleotidases into the pathobiology of some
      cardiovascular disorders and the need to develop a novel pharmacology based on
      those recent findings.

PMID- 23000391
TI  - Hyperresponsiveness to adenosine in sensitized Wistar rats over-expressing A1
      receptor.
AB  - Airway hyperreactivity is characterized by increased responsiveness to
      bronchoconstrictor stimuli and it is hallmark of asthma. Adenosine is an
      ubiquitous signaling nucleoside resulting from ATP catabolism, whose
      extracellular levels increase following cellular damage or stress. Adenosine
      plays a role in asthma; asthmatics, but not normal subjects, present
      bronchoconstriction following inhalation of adenosine or of its precursor,
      adenosine-5'-monophosphate, most likely via adenosine A(2B) receptor on mast
      cells. However, the mechanism underling the increased airway smooth muscle
      sensitivity to adenosine in asthmatics remains to be elucidated. Early
      experimental studies suggested the involvement of A(1) receptor; this hypothesis
      has been confirmed by more recent studies on guinea pigs and is corroborated by
      the finding of an increased adenosine A(1) expression on asthmatic bronchial
      tissues. Brown Norway rats, the strain usually used to assess asthma models,
      develop hyperresponsiveness to adenosine 3h following allergen challenge, but not
      24h thereafter, without involvement of A(1) receptor. Here, we investigated the
      role of adenosine A(1) receptor in sensitized Wistar rats showing airway
      hyperresponsiveness 24h following allergen challenge. We found that on bronchi of
      sensitized Wistar rats challenged with allergen there is an increased adenosine
      A(1) receptor expression on smooth muscle that is responsible for
      hyperresponsiveness to adenosine and ovalbumin.

PMID- 23000392
TI  - 6-[(1-naphthylmethyl)sulfanyl]-9H-purine induces G2/M phase arrest and apoptosis
      in human hepatocellular carcinoma HepG2 cells.
AB  - Due to the increasing incidence of cancer, a leading cause of death worldwide,
      discovery of new therapeutic drugs is urgently needed. By screening for agents
      with low toxicity that selectively target cancer cells, we found that 6-[(1
      naphthylmethyl) sulfanyl]-9H-purine (NMMP), a derivative of 6-mercaptopurine (6
      MP), could reduce the viability of five human cancer cell lines. Further study
      suggested that NMMP inhibition of the proliferation of hepatocellular carcinoma
      (HepG2) cells was associated with G2/M phase cell cycle arrest, and reduced
      cyclin-dependent kinase (CDK) 4 and cyclin B1/D1 levels. In addition, NMMP
      induced cell apoptosis, as determined by TUNEL assay. Immunoblot analysis
      revealed that the expression of cleaved caspase-9 and caspase-3 as well as the
      ratio of Bax/Bcl-2 protein increased significantly. Overall, our results suggest
      that NMMP exerts anti-tumor activities through induction of G2/M phase arrest and
      mitochondria-dependent cell apoptosis, implicating its potential therapeutic
      value for the treatment of cancer.

PMID- 23000393
TI  - Direct electrochemistry of alcohol oxidase using multiwalled carbon nanotube as
      electroactive matrix for biosensor application.
AB  - Rapid detection of alcohol is important in clinical diagnosis and fermentation
      industry. An octameric alcohol oxidase (AOx) (Mr 675 kDa) from Pichia pastoris,
      immobilized on multiwalled carbon nanotubes-Nafion(r) (MWCNT-Nf) matrix and
      encapsulated with polyethylenimine (PEI) on gold electrode (AuE), showed a redox
      peak at 0.21V (vs. Ag/AgCl electrode at pH 7.5) for oxidation of alcohol. The
      electron transfer rate constant and surface coverage of the immobilized AOx were
      1.69+/-0.15 s-1 and 2.43*10-12 mol cm-2, respectively. Studies on response and
      kinetics of Au-MWCNT-Nf-AOx-PEI bioelectrodes for alcohol showed a linear
      response in the range of 8 MUM-42 MUM, response time of 55 s for steady state
      current, and detection limit of 5 MUM. The bioelectrode retains ~90% of the
      original response even after four weeks when stored in potassium phosphate buffer
      pH 7.5 at 4  degrees C. The fabricated bioelectrode was found to exclude
      interference caused by the common electroactive species such as ascorbic acid,
      uric acid, lactic acid, glucose and urea. The bioelectrode also showed reliable
      response characteristics in blood serum samples. The findings of the
      investigation have established the direct electrochemistry of the AOx protein and
      its potential biosensor application for quantitative detection of alcohol in
      blood serum.

PMID- 23000394
TI  - Phosphatidylcholine-specific phospholipase C/heat shock protein 70
      (Hsp70)/transcription factor B-cell translocation gene 2 signaling in rat bone
      marrow stromal cell differentiation to cholinergic neuron-like cells.
AB  - Although bone marrow stromal cells (BMSCs) can differentiate into neuron-like
      cells, the mechanisms underlying neuronal differentiation are not well
      understood. We recently found that inhibition of phosphatidylcholine-specific
      phospholipase C (PC-PLC) by its inhibitor D609 promoted BMSCs' differentiation
      into cholinergic neuron-like cells. Using the effective small molecule D609 and
      gene microarray technology, we investigated the change of gene expression profile
      to identify key mediators involved in the neuronal differentiation. We selected
      heat shock protein 70 (Hsp70) and transcription factor B-cell translocation gene
      2 (Btg2) that were maximally up-regulated for further study. We found that
      functional suppression of Hsp70 blocked D609-induced increase of Btg2 expression
      and cholinergic neuronal differentiation of BMSCs. These results demonstrated
      that Hsp70 was the pivotal factor in PC-PLC-medicated neuronal differentiation of
      BMSCs, and Btg2 might be its downstream target. Our findings provide new clues
      for controlling BMSCs' differentiation into cholinergic neuron-like cells and
      provide a putative strategy for neurodegenerative diseases therapies.

PMID- 23000395
TI  - ATPA induced GluR5-containing kainite receptor S-nitrosylation via activation of
      GluR5-Gq-PLC-IP(3)R pathway and signalling module GluR5.PSD-95.nNOS.
AB  - GluR5-containing kainite receptor (GluR5-KAR) plays an important role in the
      pathophysiology of nervous system diseases, while S-nitrosylation exerts a
      variety of effects on biological systems. However, the mechanism of GluR5-KAR S
      nitrosylation is still unclear up to now. Here our researches found that GluR5
      KAR selective agonist ATPA stimulation activated the nonclassical GluR5-KAR-Gq
      PLC-IP(3)R pathway and the signalling module GluR5.PSD-95.nNOS (the former is
      more important), led to Ca(2+) release from intracellular calcium stores
      endoplasmic reticulum (ER) to cytoplasm and extracellular calcium indrawal,
      respectively, which further resulted in nNOS activation and GluR5-KAR S
      nitrosylation, and then inhibited GluR5-mediated whole-cell current attenuation
      and induced apoptosis in primary cultured hippocampal neurons. Clarification of
      the primary mechanisms of GluR5-KAR S-nitrosylation induced by ATPA and
      identification of critical cysteine for GluR5-2a S-nitrosylation (Cys231 and
      Cys804) open up a brand-new field for revealing downstream signalling pathway of
      GluR5-KAR and its molecular characteristics, exploring the pathogenesis of
      neurological diseases and searching for promising therapies.

PMID- 23000397
TI  - Maternal-fetal resource allocation.

PMID- 23000396
TI  - Genetics and infectivity of H5N1 highly pathogenic avian influenza viruses
      isolated from chickens and wild birds in Japan during 2010-11.
AB  - Outbreaks of H5N1 subtype highly pathogenic avian influenza virus (HPAIV) were
      recorded in chickens, domesticated birds and wild birds throughout Japan from
      November 2010 to March 2011. Genetic analysis of the Japanese isolates indicated
      that all gene segments, except the PA gene, were closely related to Japanese wild
      bird isolates in 2008 and belonged to clade 2.3.2.1 classified by the WHO/OIE/FAO
      H5N1 Evolution Working Group. Direct ancestors of the PA gene segment of all
      Japanese viruses analyzed in this study can be found in wild bird strains of
      several subtypes other than H5N1 isolated between 2007 and 2009. The PA gene of
      these wild bird isolates share a common ancestor with H5N1 HPAIVs belonging to
      clades 2.5, 7 and 9, indicating that wild birds were involved in the emergence of
      the current reassortant 2.3.2.1 viruses. To determine how viruses were maintained
      in the wild bird population, two isolates derived from chickens
      (A/chicken/Shimane/1/2010, Ck10 and A/chicken/Miyazaki/S4/2011, CkS411) and one
      from a wild bird (A/mandarin duck/Miyazaki/22M-765/2011, MandarinD11) were
      compared in their ability to infect and be transmitted to chickens. There was a
      significant difference in the survival of chickens that were infected with
      10(6)EID(50) of CkS411 compared to those with MandarinD11 and the transmission
      efficiency of CkS411 was greater than the other viruses. The increased titer of
      CkS411 excreted from infected chickens contributed to the improved transmission
      rates. It was considered that reduced virus excretion and transmission of
      MandarinD11 could have been due to adaptation of the virus in wild birds.

PMID- 23000399
TI  - Testosterone deficiency accompanied by testicular and epididymal abnormalities in
      TMF(-/-) mice.
AB  - TMF/ARA160 is a Golgi-associated protein, which is essential for spermiogenesis.
      In this study, we show that lack of TMF/ARA160 leads to defects in both the
      testis and the epididymis. In the testis, spermatid retention and extensive
      proliferation of Leydig cells were observed. Concomitantly, the serum levels of
      luteinizing hormone (LH), a stimulator of Leydig cell proliferation, were
      significantly increased in TMF(-/-) mice. Structural and functional defects were
      also seen in the epididymis. These included apoptosis of epithelial epididymal
      cells and sperm stasis in the cauda. Notably, the serum testosterone levels of
      TMF(-/-) mice were significantly lower than those of wt mice, and external
      testosterone administration decreased the number of apoptotic epithelial
      epididymal cells in TMF(-/-) animals. In summary, we show here for the first time
      that TMF/ARA160 participates in the control of serum testosterone levels in
      males, and its absence results in major testicular and epididymal defects.

PMID- 23000400
TI  - Oral brush biopsy analysis by MALDI-ToF Mass Spectrometry for early cancer
      diagnosis.
AB  - OBJECTIVES: Intact cell peptidome profiling (ICPP) with MALDI-ToF Mass
      Spectrometry holds promise as a non-invasive method to detect head and neck
      squamous cell carcinoma (HNSCC) objectively, which may significantly improve the
      early diagnosis of oral cancer. The present study was designed to discriminate
      between tumour samples and non-cancer controls (healthy mucosa and oral lesions)
      by analysing complete spectral patterns of intact cells using MALDI-ToF MS.
      MATERIALS AND METHODS: In the first step, a database consisting of 26 patients
      suffering from HNSCC was established by taking brush biopsy samples of the
      diseased area and of the healthy buccal mucosa of the respective contralateral
      area. After performing MALDI-ToF MS on these samples, classification analysis was
      used as the basis for further classification of an additional 26 blinded samples
      including HNSCC, oral lesions and healthy mucosa. RESULTS: By analysing spectral
      patterns of the blinded samples, all cancerous lesions were defined accurately.
      One incorrect evaluation (false positive) occurred in the lesion cohort, leading
      to a sensitivity of 100%, a specificity of 93% and an overall accuracy of 96.5%.
      CONCLUSION: ICPP using MALDI-ToF MS is able to distinguish between healthy and
      cancerous mucosa and between oral lesions and oral cancer with excellent
      sensitivity and specificity, which may lead to more accurate early diagnosis of
      HNSCC.

PMID- 23000398
TI  - Family members CREB and CREM control thyrotropin-releasing hormone (TRH)
      expression in the hypothalamus.
AB  - Thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the
      hypothalamus is regulated by thyroid hormone (TH). cAMP response element binding
      protein (CREB) has also been postulated to regulate TRH expression but its
      interaction with TH signaling in vivo is not known. To evaluate the role of CREB
      in TRH regulation in vivo, we deleted CREB from PVN neurons to generate the
      CREB1(DeltaSIM1) mouse. As previously shown, loss of CREB was compensated for by
      an up-regulation of CREM in euthyroid CREB1(DeltaSIM1) mice but TSH, T4 and T3
      levels were normal, even though TRH mRNA levels were elevated. Interestingly, TRH
      mRNA expression was also increased in the PVN of CREB1(DeltaSIM1) mice in the
      hypothyroid state but became normal when made hyperthyroid. Importantly, CREM
      levels were similar in CREB1(DeltaSIM1) mice regardless of thyroid status,
      demonstrating that the regulation of TRH by T3 in vivo likely occurs
      independently of the CREB/CREM family.

PMID- 23000401
TI  - Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic beta cell
      fate in response to cytokines.
AB  - Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory
      and iron-overload diseases. Little is known about iron transport regulation
      during inflammatory attack. Through a combination of in vitro and in vivo
      studies, we show that the proinflammatory cytokine IL-1beta induces divalent
      metal transporter 1 (DMT1) expression correlating with increased beta cell iron
      content and ROS production. Iron chelation and siRNA and genetic knockdown of
      DMT1 expression reduce cytokine-induced ROS formation and cell death. Glucose
      stimulated insulin secretion in the absence of cytokines in Dmt1 knockout islets
      is defective, highlighting a physiological role of iron and ROS in the regulation
      of insulin secretion. Dmt1 knockout mice are protected against multiple low-dose
      streptozotocin and high-fat diet-induced glucose intolerance, models of type 1
      and type 2 diabetes, respectively. Thus, beta cells become prone to ROS-mediated
      inflammatory damage via aberrant cellular iron metabolism, a finding with
      potential general cellular implications.

PMID- 23000402
TI  - Expanding roles for SREBP in metabolism.
AB  - Sterol regulatory element-binding protein (SREBP) transcription factors regulate
      cellular lipogenesis and lipid homeostasis. Recent studies reveal expanding roles
      for SREBPs with the description of new regulatory mechanisms, the identification
      of unexpected transcriptional targets, and the discovery of functions for SREBPs
      in type II diabetes, cancer, immunity, neuroprotection, and autophagy.

PMID- 23000403
TI  - Many mouths to feed: the control of food intake during lactation.
AB  - Providing nutrients to their developing young is perhaps the most energetically
      demanding task facing female mammals. In this paper we focus primarily on studies
      carried out in rats to describe the changes in the maternal brain that enable the
      dam to meet the energetic demands of her offspring. In rats, providing milk for
      their litter is associated with a dramatic increase in caloric intake, a
      reduction in energy expenditure and changes in the pattern of energy utilization
      as well as storage. These behavioral and physiological adaptations result, in
      part, from alterations in the central pathways controlling energy balance.
      Differences in circulating levels of metabolic hormones such as leptin, ghrelin
      and insulin as well as in responsiveness to these signals between lactating and
      nonlactating animals, contribute to the modifications in energy balance pathways
      seen postpartum. Suckling stimulation from the pups both directly, and through
      the hormonal state that it induces in the mother, plays a key role in
      facilitating these adaptations.

PMID- 23000404
TI  - Analysis of particle kinematics in spheronization via particle image velocimetry.
AB  - Spheronization is a wide spread technique in pellet production for many
      pharmaceutical applications. Pellets produced by spheronization are characterized
      by a particularly spherical shape and narrow size distribution. The particle
      kinematic during spheronization is currently not well-understood. Therefore,
      particle image velocimetry (PIV) was implemented in the spheronization process to
      visualize the particle movement and to identify flow patterns, in order to
      explain the influence of various process parameters. The spheronization process
      of a common formulation was recorded with a high-speed camera, and the images
      were processed using particle image velocimetry software. A crosscorrelation
      approach was chosen to determine the particle velocity at the surface of the
      pellet bulk. Formulation and process parameters were varied systematically, and
      their influence on the particle velocity was investigated. The particle stream
      shows a torus-like shape with a twisted rope-like motion. It is remarkable that
      the overall particle velocity is approximately 10-fold lower than the tip speed
      of the friction plate. The velocity of the particle stream can be correlated to
      the water content of the pellets and the load of the spheronizer, while the
      rotation speed was not relevant. In conclusion, PIV was successfully applied to
      the spheronization process, and new insights into the particle velocity were
      obtained. 

PMID- 23000405
TI  - An inexpensive Arduino-based LED stimulator system for vision research.
AB  - Light emitting diodes (LEDs) are being used increasingly as light sources in life
      sciences applications such as in vision research, fluorescence microscopy and in
      brain-computer interfacing. Here we present an inexpensive but effective visual
      stimulator based on light emitting diodes (LEDs) and open-source Arduino
      microcontroller prototyping platform. The main design goal of our system was to
      use off-the-shelf and open-source components as much as possible, and to reduce
      design complexity allowing use of the system to end-users without advanced
      electronics skills. The main core of the system is a USB-connected Arduino
      microcontroller platform designed initially with a specific emphasis on the ease
      of-use creating interactive physical computing environments. The pulse-width
      modulation (PWM) signal of Arduino was used to drive LEDs allowing linear light
      intensity control. The visual stimulator was demonstrated in applications such as
      murine pupillometry, rodent models for cognitive research, and heterochromatic
      flicker photometry in human psychophysics. These examples illustrate some of the
      possible applications that can be easily implemented and that are advantageous
      for students, educational purposes and universities with limited resources. The
      LED stimulator system was developed as an open-source project. Software interface
      was developed using Python with simplified examples provided for Matlab and
      LabVIEW. Source code and hardware information are distributed under the GNU
      General Public Licence (GPL, version 3).

PMID- 23000406
TI  - Model for studying Clostridium botulinum neurotoxin using differentiated motor
      neuron-like NG108-15 cells.
AB  - Cancerous cell lines have traditionally shown low sensitivity to laboratory or
      pharmaceutical preparations of botulinum neurotoxin. The work presented here
      demonstrates that the mouse neuroblastoma/rat glioma hybrid cell line NG108-15 is
      capable of more sensitively detecting BoNT/A1 than any cell line previously
      described. This cell line has previously been described to have motor neuron like
      characteristics, therefore making it a good model to study BoNTs. Differentiation
      of NG108-15 cells in serum-free medium containing retinoic acid and purmorphamine
      dramatically increased sensitivity of the neurons to BoNT/A (EC(50) = ~16 LD(50)
      U). Additional pre-treatment with triasialoganglioside GT1B prior to toxin
      exposure reduced the EC(50) further to ~11 LD(50) U. Co-culture of the neurons
      with C2C12 myotubes also significantly increased BoNT/A sensitivity of NG108-15
      cells (EC(50) = 26 U) in the absence of differentiation factors.

PMID- 23000407
TI  - Acetoacetyl-CoA synthetase is essential for normal neuronal development.
AB  - Cholesterol and fatty acids are essential, abundant components of neuronal
      tissue. Acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme for
      the synthesis of cholesterol and fatty acids and is highly expressed in the
      brain. In this study, we investigated the regulation of AACS during neurite
      outgrowth to clarify the physiological role of AACS in neurogenesis. Messenger
      RNA levels and the expression of AACS were increased during neurite outgrowth in
      Neuro-2a cells. The expression of HMG-CoA reductase, a key enzyme of cholesterol
      biosynthesis, was also increased. ChIP assays showed that the amount of SREBP-2,
      a key transcription factor of cholesterol synthesis, interacted with the AACS
      promoter was increased during neurite outgrowth, and knockdown of SREBP-2 down
      regulated the mRNA levels of AACS in Neuro-2a cells. The expression of AACS in
      the brains of mouse embryos was dramatically increased between E16.5 and E18.5.
      Moreover, knockdown of AACS in primary neurons caused decreases in the expression
      of MAP-2 and NeuN, which are markers of neuronal differentiation, as well as
      synaptopodin, a marker of spine apparatus. These results suggest that AACS is
      regulated by SREBP-2 and involves in the normal development of neurons.

PMID- 23000408
TI  - Rapid dimerization of quercetin through an oxidative mechanism in the presence of
      serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells.
AB  - Quercetin is a member of the flavonoid family and has been previously shown to
      have a variety of anti-cancer activities. We and others have reported anti
      proliferation, cell cycle arrest, and induction of apoptosis of cancer cells
      after treatment with quercetin. Quercetin has also been shown to undergo
      oxidation. However, it is unclear if quercetin or one of its oxidized forms is
      responsible for cell death. Here we report that quercetin rapidly oxidized in
      cell culture media to form a dimer. The quercetin dimer is identical to a dimer
      that is naturally produced by onions. The quercetin dimer and quercetin-3-O
      glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231
      cells. Finally, supplementing the media with ascorbic acid increases quercetin's
      ability to induce cell death probably by reduction oxidative dimerization. Our
      results suggest that an unmodified quercetin is the compound that elicits cell
      death.

PMID- 23000409
TI  - Binding of carboxypeptidase N to fibrinogen and fibrin.
AB  - The ultimate step in the blood coagulation cascade is the formation of fibrin.
      Several proteins are known to bind to fibrin and may thereby change clot
      properties or clot function. Our previous studies identified carboxypeptidase N
      (CPN) as a novel plasma clot component. CPN cleaves C-terminal lysine and
      arginine residues from several proteins. The activity of CPN is increased upon
      its proteolysis by several proteases. The aim of this study is to investigate the
      presence of CPN in a plasma clot in more detail. Plasma clots were formed by
      adding thrombin, CaCl(2) and aprotinin to citrated plasma. Unbound proteins were
      washed away and non-covalently bound proteins were extracted and analyzed with 2D
      gel electrophoresis and mass spectrometry. The identification of CPN as a fibrin
      clot-bound protein was verified using Western blotting. Clot-bound CPN consisted
      of the same molecular forms as CPN in plasma and its content was approximately 30
      ng/ml plasma clot. Using surface plasmon resonance we showed that CPN can bind to
      fibrinogen as well as to fibrin. In conclusion, CPN binds to fibrinogen and is
      present in a fibrin clot prepared from plasma. Because CPN binds to a fibrin
      clot, there could be a possible role for CPN as a fibrinolysis inhibitor.

PMID- 23000410
TI  - Functional characterization of the heterodimeric sweet taste receptor T1R2 and
      T1R3 from a New World monkey species (squirrel monkey) and its response to sweet
      tasting proteins.
AB  - The family C G protein-coupled receptor (GPCR) T1R2 and T1R3 heterodimer
      functions as a broadly acting sweet taste receptor. Perception of sweet taste is
      a species-dependent physiological process. It has been widely reported that New
      World monkeys and rodents are not able to perceive some of the artificial
      sweeteners and sweet-tasting proteins that can be perceived by humans, apes, and
      Old World monkeys. Until now, only the sweet receptors of humans, mice and rats
      have been functionally characterized. Here we report characterization of the
      sweet taste receptor (T1R2/T1R3) from a species of New World primate, squirrel
      monkey. Our results show that the heterodimeric receptor of squirrel monkey does
      not respond to artificial sweeteners aspartame, neotame, cyclamate, saccharin and
      sweet-tasting protein monellin, but surprisingly, it does respond to thaumatin at
      high concentrations (>18 MUM). This is the first report demonstrating that
      species of New World monkey can perceive some specific sweet-tasting proteins.
      Furthermore, the sweet receptor of squirrel monkey responses to the such
      sweeteners cannot be inhibited by the sweet inhibitor lactisole. We compared the
      response differences of the squirrel monkey and human receptors and found that
      the residues in T1R2 determine species-dependent sweet taste toward saccharin,
      while the residues in either T1R2 or T1R3 are responsible for the sweet taste
      difference between humans and squirrel monkeys toward monellin. Molecular models
      indicated that electrostatic properties of the receptors probably mediate the
      species-dependent response to sweet-tasting proteins.

PMID- 23000411
TI  - Domain 5 of high molecular weight kininogen inhibits collagen-mediated cancer
      cell adhesion and invasion in association with alpha-actinin-4.
AB  - High molecular weight kininogen (HK) is a plasma glycoprotein with multiple
      functions, including the regulation of coagulation. We previously demonstrated
      that domain 5 (D5(H)), a functional domain of HK, and its derived peptides played
      an important role in the vitronectin-mediated suppression of cancer cell adhesion
      and invasion. However, the underlying mechanisms of the D5(H)-mediated
      suppressive effects remain to be elucidated. Here, we showed that D5(H) and its
      derivatives inhibited the collagen-mediated cell adhesion and invasion of human
      osteosarcoma MG63 cells. Using purified D5(H) fused to glutathione-S-transferase
      (GST) and D5(H)-derived peptides for column chromatography, an actin-binding
      protein, alpha-actinin-4, was identified as a binding protein of D5(H) with high
      affinity for P-5m, a core octapeptide of D5(H). Immunofluorescence microscopy
      demonstrated that D5(H) co-localized with alpha-actinin-4 inside MG63 cells. In
      addition, exogenous GST-D5(H) added to the culture media was transported into
      MG63 cells, although GST alone as a control was not. As alpha-actinin-4 regulates
      actin polymerization necessary for cell adhesion and is related to the integrin
      dependent attachment of cells to the extracellular matrix, our results suggest
      that D5(H) may modulate cell adhesion and invasion together with actinin-4.

PMID- 23000412
TI  - The regulation of trefoil factor 2 expression by the transcription factor Sp3.
AB  - Trefoil factor family 2 (TFF2) participates in mucus stabilization and repair,
      apoptosis, and inflammatory responses. Previously published reports have
      indicated that several growth factors and basal transcription factors are
      associated with the expression of TFF2. However, the detailed mechanisms that
      regulate TFF2 expression are not fully understood. The present study was designed
      to assess the essential role of the transcription factor SP3 with respect to TFF2
      expression. We first demonstrated that there was a negative correlation between
      the expression levels of SP3 and TFF2. Thus, in the examined cells, the
      overexpression of SP3 decreased the expression level of TFF2, whereas the
      inhibition of SP3 increased the expression level of TFF2. Moreover, we discovered
      two GC boxes in the TFF2 promoter and confirmed the specific binding of SP3 to
      this promoter. On the whole, this study indicated that Sp3 was a major regulator
      of TFF2 expression. This knowledge should contribute to our understanding of the
      role that is played by SP3 in the regulation of TFF2 expression.

PMID- 23000413
TI  - Induction of REDD1 gene expression in the liver in response to endoplasmic
      reticulum stress is mediated through a PERK, eIF2alpha phosphorylation, ATF4
      dependent cascade.
AB  - Since the endoplasmic reticulum (ER) plays a vital role in hepatocyte function,
      it is not surprising that a variety of liver-related diseases are associated with
      ER stress. As in other tissues, ER stress in the liver leads to generation of the
      unfolded-protein response resulting in activation of a transcriptional program
      that promotes restoration of homeostasis within the lumen of the ER. Previous
      studies using cells in culture demonstrated that ER stress induces expression of
      REDD1 (regulated in development and DNA damage responses), a potent repressor of
      signaling through the protein kinase referred to as the mechanistic target of
      rapamycin in complex 1 (mTORC1). In the present study, the results from the cell
      culture experiments were extended to show that tunicamycin-mediated ER stress in
      the liver in vivo also induces REDD1 gene expression. Moreover, the induction of
      REDD1 gene expression was shown to require the protein kinase PERK and enhanced
      phosphorylation of its substrate, the alpha-subunit of eukaryotic initiation
      factor 2.

PMID- 23000414
TI  - Regulation of ITAM adaptor molecules and their receptors by inhibition of
      calcineurin-NFAT signalling during late stage osteoclast differentiation.
AB  - Osteoclasts are specialised bone resorptive cells responsible for both
      physiological and pathological bone loss. Osteoclast differentiation and activity
      is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with
      its receptor RANK to induce the transcription factor, nuclear factor of activated
      T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor
      tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a
      co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and
      triggering receptor expressed in myeloid cells (TREM2) are essential receptors
      that pair with adaptor molecules Fc receptor common gamma chain (FcRgamma) and
      DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling.
      Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT
      (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in
      osteoclast differentiation and activity. This study aimed to investigate the
      effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM
      factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3
      integrin (beta3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear
      cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating
      factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT.
      Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP))
      and activity (assessed by dentine pit resorption) were significantly reduced with
      treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis
      demonstrated that FK506 treatment significantly (p<0.05) reduced the expression
      of NFATc1, CathK, OSCAR, FcRgamma, TREM2 and DAP12 during the terminal stage of
      osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK,
      OSCAR, FcRgamma, and AnnVIII, gene expression. This data suggest FK506 and VIVIT
      act differently in targeting the calcineurin-NFAT signalling cascade to suppress
      key mediators of the ITAM pathway during late stage osteoclast differentiation
      and this is associated with a reduction in both osteoclast differentiation and
      activity.

PMID- 23000415
TI  - The chemical composition of smokeless tobacco: a survey of products sold in the
      United States in 2006 and 2007.
AB  - Selected toxicant concentrations and other chemical measures have been determined
      for 43 U.S. smokeless tobacco products sold in 2006 and 2007. Products evaluated
      included moist snuff, dry snuff, loose leaf, plug, dissolvable and snus tobacco
      brands. Reference products available for scientific research purposes and eleven
      Swedish products were also evaluated and compared to the commercial products
      studied. Chemical endpoints determined included benzo[a]pyrene (B[a]P), N'
      nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB), 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-Nitrosodimethylamine
      (NDMA), nitrite, cadmium, lead, arsenic, nickel, chromium, chloride, water, pH
      and nicotine. Different toxicant profiles were observed for the products studied,
      with snus tobacco brands generally containing relatively low concentrations of
      B[a]P and tobacco specific nitrosamines (TSNAs) compared to other moist snuffs.
      Smokeless tobacco reference product toxicant profiles were similar to
      corresponding commercial products, with the exception of the TSNA content of the
      dry snuff reference material. TSNA concentrations observed for all commercial
      products were lower than historically reported values, likely reflecting changes
      in product shelf life, tobacco curing practices and, possibly, product blend
      formulations during the last 20-30 years. The survey results summarized provide a
      temporal point of comparison with future data anticipated from FDA "harmful and
      potentially harmful constituents in tobacco products" reporting.

PMID- 23000416
TI  - Synergetic toxicity of DATR, a recombinant soluble human TRAIL mutant, in
      combination with traditional chemotherapeutics in rats.
AB  - The recombinant soluble human TRAIL mutant (DATR), derived from tumour necrosis
      factor-related apoptosis-inducing ligand (TRAIL), is a promising agent for cancer
      therapy. The present study evaluated the synergetic toxicity of DATR in
      combination with traditional chemotherapeutics, including irinotecan, polyene
      paclitaxel and oxaliplatin in rats. Rats treated with polyene paclitaxel alone or
      in combination with DATR showed severe diarrhea, appetite inhibition, increasing
      sodium (Na(+)), potassium (Cl(-)) and glucose (GLU) and serious disorders in the
      haematological system. Increasing total bilirubin (TBIL) and blood urea nitrogen
      (BUN) were detected in the rats treated with oxaliplatin alone or in combination
      with DATR. Furthermore, except that the BUN and Crea of male rats treated with
      irinotecan in combination with DATR were higher than those of treated with
      irinotecan, the addition of DATR does not increase the toxicity induced by
      irinotecan, polyene paclitaxel and oxaliplatin. In conclusion, DATR probably
      increases kidney lesions of rat with irinotecan, but does not increase the
      toxicity induced by polyene paclitaxel and oxaliplatin. This indicated that DATR
      has promising potential in clinical combination therapies. Furthermore, the
      toxicity induced by DATR on the liver, kidneys and haematological system should
      be considered carefully if DATR is used in combination with traditional
      chemotherapeutics.

PMID- 23000417
TI  - Intra- and inter-individual variability in urinary nicotine excretion and plasma
      cotinine in adult cigarette smokers.
AB  - Urinary nicotine equivalents (NE) and plasma cotinine are widely used as a
      biomarker for exposure to tobacco products, but there is limited information on
      intra- and inter-individual variability in the literature. Data were gathered
      from 13 randomized controlled clinical studies sponsored by Philip Morris USA,
      with study durations between 2 and 8 days for the short term (ST) and 3-12 months
      for the long term (LT) studies. Coefficients of variation (CV) were compared and
      a linear mixed model was used to partition the total study variability into inter
      and intra-individual variability. In the ST and LT studies respectively, the
      root-mean-square (RMS) intra-individual CV was 19% and 29% for NE (mg/24 h); 19%
      and 33% for NE (mg/cig) and 13% and 22% for plasma cotinine. The RSM inter
      individual CV was 38% and 38% for NE (mg/24h), 25% and 32% for NE (mg/cig) and
      38% and 37% for plasma cotinine, in ST and LT study, respectively. Intra
      individual CV was smaller in ST studies than in LT studies, and was significantly
      less than inter-individual CV in ST studies. Daily cigarette consumption alone
      could not explain all the variability in NE and plasma cotinine. The variability
      estimates could be used for clinical study design of clinical and developing
      regulatory guidance.

PMID- 23000419
TI  - [Proposal for the modification of metformin use in patients with chronic kidney
      disease].
AB  - Metformin is the first-line, widely used oral antidiabetic agent for the
      management of type 2 diabetes. There is increasing evidence that metformin use
      results in a reduction in cardiovascular morbidity and mortality, and might have
      anticancer activity. An extremely rare, but potentially life-threatening adverse
      effect of metformin is lactic acidosis, therefore, its use is traditionally
      contraindicated if the glomerular filtrate rate is below 60 mL/min. However,
      lactic acidosis is always associated with acute events, such as hypovolemia,
      acute cardiorespiratory illness, severe sepsis and acute renal or hepatic
      failure. Furthermore, administration of insulins and conventional
      antihyperglycemic agents increases the risk of severe hypoglycemic events when
      renal function is reduced. Therefore, the magnitude of the benefit of metformin
      use would outweigh potential risk of lactic acidosis in moderate chronic renal
      disease. After reviewing the literature, the authors give a proposal for the
      administration of metformin, according to the calculated glomerular filtrate
      rate.

PMID- 23000420
TI  - [Trends and current questions of cardiovascular prevention in primary health
      care].
AB  - Although an impressive progress has been achieved in the treatment of
      cardiovascular diseases, they are at the top of the mortality statistics in
      Hungary. Prevention of these diseases is an essential task of the primary health
      care. Cardiovascular prevention is carried out at primary, secondary and tertiary
      levels using risk group and population preventive strategies. The two main tasks
      of primary cardiovascular prevention are health promotion and cardiovascular
      disease prevention, and its main programs are ensuring healthy nutrition,
      improving physical training and accomplishing an anti-smoking program. The
      essential form of secondary prevention is the screening activity of the primary
      health care. The majority of cardiovascular risk factors can be discovered during
      the doctor-patient consultation, but laboratory screening is needed for assessing
      metabolic risks. The official screening rules of the cardiovascular risk factors
      and diseases are based on diagnostic criteria of the metabolic syndrome; however,
      nowadays revealing of global cardiometabolic risks is also necessary. In patients
      without cardiovascular diseases but with risk factors, a cardiovascular risk
      estimation has to be performed. In primary care, there is a possibility for long
      term follow-up and continuous care of patients with chronic diseases, which is
      the main form of the tertiary prevention. In patients with cardiovascular
      diseases, ranking to cardiovascular risk groups is a very important task since
      target values of continuous care depend on which risk group they belong to. The
      methods used during continuous care are lifestyle therapy, specific
      pharmacotherapy and organ protection with drugs. Combined health education and
      counselling is the next element of the primary health care prevention; it is a
      tool that helps primary, secondary and tertiary prevention. Changes needed for
      improving cardiovascular prevention in primary care are the following:
      appropriate evaluation of primary prevention, health education and counselling,
      renewal of the cardiovascular screening system based on the notion of global
      cardiometabolic risk, creating a unified cardiovascular prevention guideline, and
      operating primary care cardiovascular prevention within the framework of an
      integrated prevention system.

PMID- 23000421
TI  - [Left ventricular rotation and twist of the heart. Clarification of some
      concepts].
AB  - In case of a healthy heart basal part of the left ventricle rotates clockwise in
      systole, while the apex rotates counter-clockwise. This sort of squeezing-turning
      motion is called "twisting" of the heart. The aim of the current review is to
      summarize knowledge regarding left ventricular rotation and twist as well as
      methodological aspects of their evaluation.

PMID- 23000418
TI  - Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute
      vascular inflammation in mice.
AB  - Cyclooxygenase (COX)-derived prostaglandins and cytochrome P450 (CYP) epoxygenase
      derived epoxyeicosatrienoic acids are important regulators of inflammation;
      however, functional interactions between these pathways in the regulation of
      vascular inflammation in vivo have not been studied. We investigated the relative
      and additive effects of endothelial CYP2J2 overexpression (Tie2-CYP2J2-Tr),
      global sEH disruption (Ephx2(-/-)), and pharmacologic COX inhibition with
      indomethacin on the acute vascular inflammatory response to endotoxin in mice.
      Compared to vehicle-treated wild-type C57BL/6 controls, induction of
      myeloperoxidase (MPO) activity in lung and liver was similarly attenuated in Tie2
      CYP2J2-Tr mice, Ephx2(-/-) mice and wild-type mice treated with moderate dose
      indomethacin. Dual modulation of both pathways, however, did not produce an
      additive anti-inflammatory effect. These findings demonstrate that both COX and
      CYP epoxygenase-mediated eicosanoid metabolism are important regulators of the
      acute vascular inflammatory response in vivo, and suggest that the anti
      inflammatory effects of modulating each pathway may be mediated, at least in
      part, by overlapping mechanisms. 

PMID- 23000422
TI  - [Characteristics of smoking and secondhand smoke exposure in monozygotic and
      dizygotic twins: results from an international twin study].
AB  - INTRODUCTION: Zygosity differences in smoking exposure are unclear in twins.
      AIMS: To assess smoking and secondhand smoke exposure characteristics in twins.
      METHODS: 151 monozygotic and 62 dizygotic Hungarian and American adult twin pairs
      (age 43.8+/-16.5 years, mean+/-SD) participated in the study. RESULTS:
      Monozygotic twins started smoking 1.8 years earlier compared to dizygotic twins
      (p = 0.08). Dizygotic twins smoked longer (p<0.01) and suffered more parental
      smoke exposure during childhood (p<0.05). Monozygotic twins reported stricter
      smoking restrictions at home and workplaces (p<0.005) and less smoke exposure in
      indoor public places (p<0.01). 85.7% of monozygotic twins were ex or active
      smokers, while only 69.5% of the dizygotics (p<0.01). Lesser difference was
      observed in the self-reported smoke exposure rate in monozygotic compared to
      dizygotic pairs concerning restaurants and cafes (p<0.05) which was not present
      regarding bars, pubs and transportation facilities. CONCLUSIONS: Different
      psychological family orientation may be present across zygosity. Preventive
      parental care is warranted in twin families exposed to smoking.

PMID- 23000424
TI  - Myeloid cell leukemia-1 is a key molecular target for mithramycin A-induced
      apoptosis in androgen-independent prostate cancer cells and a tumor xenograft
      animal model.
AB  - Mithramycin A (Mith) is a natural polyketide that has been used in multiple areas
      of research including apoptosis of various cancer cells. Here, we examined the
      critical role of Mith in apoptosis and its molecular mechanism in DU145 and PC3
      prostate cancer cells and tumor xenografts. Mith decreased cell growth and
      induced apoptosis in DU145 and PC-3 cells. Myeloid cell leukemia-1 (Mcl-1) was
      over-expressed in both cell lines compared to RWPE1 cells. Mith inhibited Mcl-1
      protein expression in both cells, but only altered Mcl-1 mRNA levels in PC-3
      cells. We also found that Mith reduced Mcl-1 protein levels through both
      proteasome-dependent protein degradation and the inhibition of protein synthesis
      in DU145 cells. Studies using siRNA confirmed that the knockdown of Mcl-1 induced
      apoptosis. Mith significantly suppressed TPA-induced neoplastic cell
      transformation through the down-regulation of the Mcl-1 protein in JB6 cells, and
      suppressed the transforming activity of both cell types. Mith also inhibited
      tumor growth and Mcl-1 levels, in addition to inducing apoptosis, in athymic nude
      mice bearing DU145 cell xenografts without affecting five normal organs.
      Therefore, Mith inhibits cell growth and induces apoptosis by suppressing Mcl-1
      in both prostate cancer cells and xenograft tumors, and thus is a potent
      anticancer drug candidate for prostate cancer.

PMID- 23000426
TI  - Tumor-associated primo vascular system is derived from xenograft, not host.
AB  - The primo vascular system (PVS), which is composed of very small primo-vessels
      (PV) and primo-nodes (PN), has recently emerged as a third component of
      circulatory system. Here, we report the presence of a tumor derived PVS in murine
      xenografts of human histiocytic lymphoma (U937) in close proximity to the tumor.
      Within this system, PNs are small (~500-600 MUM diameter) membranous sac-like
      structures which contain numerous small cells which can be demonstrated by DAPI
      staining. Hematoxylin and Eosin (H&E) staining of the peri-tumoral PVS shows the
      presence of loose structures lined by fibroblasts but filled with dense fibers,
      cells, lacunae and nerve-like structures. The origin and type of cells within the
      PVS was characterized by immunostaining with antibodies for CD68, CD45 and
      lysozyme. The results of these studies reveal that the PVS of the xenograft
      originates from the human U937 tumor cells. qRT-PCR analysis of mRNA isolated
      from PVS cells reveals a striking predominance of human, rather than mouse,
      sequences. Of particular interest, human stem cell specific transcription factors
      were overexpressed, most notably KLF4, an upstream regulator of NANOG which
      maintains the pluripotent and undifferentiated state of stem cells. These results
      suggest that the cells present within the PVS are derived from the human
      xenograft and suggests that the primo-vessels associated with the xenografted
      tumor may provide a safe haven for a select population of cancer stem cells.
      Further understanding of the biological properties of these cells may allow the
      development of new anti-cancer interventions.

PMID- 23000425
TI  - Distinct responses of lung and liver macrophages to acute endotoxemia: role of
      toll-like receptor 4.
AB  - Exposure to excessive quantities of bacterial-derived lipopolysaccharide (LPS) is
      associated with injury to the lung and the liver. Macrophages are thought to play
      a key role in the pathogenic response to LPS by releasing
      proinflammatory/cytotoxic mediators. Macrophage responses to LPS are mediated in
      large part by toll-like receptor 4 (TLR4). In the present studies we used C3H/HeJ
      mice, which possess a mutated nonfunctional TLR4, to examine its role in lung and
      liver macrophage responses to acute endotoxemia induced by LPS administration.
      Treatment of control C3H/HeOuJ mice with LPS (3 mg/ml, i.p.) was associated with
      a significant increase in the number of macrophages in both the lung and the
      liver. This was most prominent after 48 h, and was preceded by expression of
      proliferating cell nuclear antigen (PCNA), suggesting that macrophage
      proliferation contributes to the response. In liver, but not lung macrophages,
      LPS administration resulted in a rapid (within 3 h) increase in mRNA expression
      of Mn superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), key enzymes in
      antioxidant defense. In contrast, HO-1 protein expression decreased 3 h after LPS
      administration in liver macrophages, while in lung macrophages it increased. mRNA
      expression of enzymes mediating the biosynthesis of eicosanoids, including
      cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), but
      not 12/15-lipoxygenase (LOX), was upregulated in liver macrophages 3-24 h after
      LPS, with no effect on lung macrophages. However, COX-2 protein expression
      increased in both cell types. Loss of functional TLR4 significantly blunted the
      effects of LPS. Thus, no major changes were observed after LPS administration in
      the number of lung and liver macrophages recovered from TLR4 mutant mice, or on
      expression of PCNA. Increases in HO-1, MnSOD, COX-2 and PGES-1 mRNA expression in
      liver macrophages were also reduced in these mice. Conversely, in lung
      macrophages, loss of functional TLR4 resulted in increased expression of COX-2
      protein and 12/15-LOX mRNA. These results demonstrate distinct lung and liver
      macrophage responses to acute endotoxemia are mediated, in part, by functional
      TLR4.

PMID- 23000427
TI  - Dual role of Response gene to complement-32 in multiple sclerosis.
AB  - Response gene to complement (RGC)-32 is a novel molecule that plays an important
      role in cell proliferation. We investigated the expression of RGC-32 in multiple
      sclerosis (MS) brain and in peripheral blood mononuclear cells (PBMCs) obtained
      from patients with relapsing-remitting multiple sclerosis. We found that CD3(+),
      CD68(+), and glial fibrillar acidic protein (GFAP)(+) cells in MS plaques co
      localized with RGC-32. Our results show a statistically significant decrease in
      RGC-32 mRNA expression in PBMCs during relapses when compared to the levels in
      stable MS patients. This decrease might be useful in predicting disease activity
      in patients with relapsing-remitting MS. RGC-32 expression was also correlated
      with that of FasL mRNA during relapses. FasL mRNA expression was significantly
      reduced after RGC-32 silencing, indicating a role for RGC-32 in the regulation of
      FasL expression. In addition, the expression of Akt1, cyclin D1, and IL-21 mRNA
      was significantly increased during MS relapses when compared to levels in healthy
      controls. Furthermore, we investigated the role of RGC-32 in TGF-beta-induced
      extracellular matrix expression in astrocytes. Blockage of RGC-32 using small
      interfering RNA significantly inhibits TGF-beta induction of procollagen I,
      fibronectin and of the reactive astrocyte marker alpha-smooth muscle actin (alpha
      SMA). Our data suggest that RGC-32 plays a dual role in MS, both as a regulator
      of T-cells mediated apoptosis and as a promoter of TGF-beta-mediated profibrotic
      effects in astrocytes.

PMID- 23000428
TI  - N-acylation of phosphatidylethanolamine and its biological functions in mammals.
AB  - N-acylphosphatidylethanolamine (NAPE) and N-acylplasmenylethanolamine (pNAPE) are
      widely found phospholipids, and they are precursors for N-acylethanolamines, a
      group of compounds that has a variety of biological effects and encompasses the
      endocannabinoid anandamide. NAPE and pNAPE are synthesized by the transfer of an
      acyl chain from a donor phospholipid, to the amine in phosphatidylethanolamine or
      plasmenylethanolamine. NAPE has been reported to stabilize model membranes during
      brain ischemia, and to modulate food intake in rodents, thus having bioactive
      effects besides its precursor role. This paper reviews the metabolism, occurrence
      and assay of NAPE and pNAPE, and discusses the putative biological functions in
      mammals of these phospholipids. This article is part of a Special Issue entitled
      Phospholipids and Phospholipid Metabolism.

PMID- 23000429
TI  - Fine tuning of the active site modulates specificity in the interaction of O
      acetylserine sulfhydrylase isozymes with serine acetyltransferase.
AB  - O-acetylserine sulfhydrylase (OASS) catalyzes the synthesis of l-cysteine in the
      last step of the reductive sulfate assimilation pathway in microorganisms. Its
      activity is inhibited by the interaction with serine acetyltransferase (SAT), the
      preceding enzyme in the metabolic pathway. Inhibition is exerted by the insertion
      of SAT C-terminal peptide into the OASS active site. This action is effective
      only on the A isozyme, the prevalent form in enteric bacteria under aerobic
      conditions, but not on the B-isozyme, the form expressed under anaerobic
      conditions. We have investigated the active site determinants that modulate the
      interaction specificity by comparing the binding affinity of thirteen
      pentapeptides, derived from the C-terminal sequences of SAT of the closely
      related species Haemophilus influenzae and Salmonella typhimurium, towards the
      corresponding OASS-A, and towards S. typhimurium OASS-B. We have found that
      subtle changes in protein active sites have profound effects on protein-peptide
      recognition. Furthermore, affinity is strongly dependent on the pentapeptide
      sequence, signaling the relevance of P3-P4-P5 for the strength of binding, and P1
      P2 mainly for specificity. The presence of an aromatic residue at P3 results in
      high affinity peptides with K(diss) in the micromolar and submicromolar range,
      regardless of the species. An acidic residue, like aspartate at P4, further
      strengthens the interaction and results in the higher affinity ligand of S.
      typhimurium OASS-A described to date. Since OASS knocked-out bacteria exhibit a
      significantly decreased fitness, this investigation provides key information for
      the development of selective OASS inhibitors, potentially useful as novel
      antibiotic agents.

PMID- 23000430
TI  - A comparative study of the cytotoxic and genotoxic effects of ICRF-154 and
      bimolane, two catalytic inhibitors of topoisomerase II.
AB  - ICRF-154 and bimolane have been used for the treatment of cancer, psoriasis, and
      uveitis in humans. Previous reports have revealed that the two drugs are
      topoisomerase II catalytic inhibitors, and patients treated with these agents
      have developed unique types of secondary leukemia. A study published in 1984 by
      Camerman and colleagues proposed that the therapeutic effects of bimolane could
      be due to ICRF-154, an impurity present within the bimolane samples that may also
      be responsible for the toxic effects attributed to bimolane. To date, this
      hypothesis has not been evaluated. In addition, little is known about the
      potential cytotoxic and genotoxic effects of ICRF-154. In this study, a
      combination of in vitro tests in human TK6 lymphoblastoid cells has been used to
      characterize the cytotoxic and genotoxic effects of ICRF-154 and bimolane as well
      as to compare the results for the two chemicals. ICRF-154 and bimolane were both
      cytotoxic, exhibiting very similar effects in three measures of cytotoxicity and
      cell proliferation. In the cytokinesis-block micronucleus assay with CREST
      antibody staining, the two agents similarly induced chromosome breakage and, to a
      lesser extent, chromosome loss. Intriguingly, both drugs resulted in the
      formation of binucleated cells, perhaps as a consequence of an interference with
      cytokinesis. To further investigate their aneugenic effects, flow cytometry and
      fluorescence in situ hybridization analyses revealed that both compounds also
      produced similar levels of non-disjunction and polyploidy. In each of the
      cellular and cytogenetic assays employed, the responses of the ICRF-154-treated
      cells were very similar to those observed with the bimolane, and generally
      occurred at equimolar test concentrations. Our results, combined with those from
      previous studies, strongly suggest that bimolane degrades to ICRF-154, and that
      ICRF-154 is most likely the chemical species responsible for the cytotoxic,
      genotoxic, and leukemogenic effects exerted by bimolane.

PMID- 23000431
TI  - Founder takes all: density-dependent processes structure biodiversity.
AB  - Density-dependent processes play a key role in the spatial structuring of
      biodiversity. Specifically, interrelated demographic processes, such as gene
      surfing, high-density blocking, and competitive exclusion, can generate striking
      geographic contrasts in the distributions of genes and species. Here, we propose
      that well-studied evolutionary and ecological biogeographic patterns of
      postglacial recolonization, progressive island colonization, microbial sectoring,
      and even the 'Out of Africa' pattern of human expansion, are fundamentally
      similar, underpinned by a 'founder takes all' density-dependent principle.
      Additionally, we hypothesize that older historic constraints of density-dependent
      processes are seen today in the dramatic biogeographic shifts that occur in
      response to human-mediated extinction events, whereby surviving lineages rapidly
      expand their ranges to replace extinct sister taxa.

PMID- 23000432
TI  - The pollen tube paradigm revisited.
AB  - The polar growth process characterizing pollen tube elongation has attracted
      numerous modeling attempts over the past years. While initial models focused on
      recreating the correct cellular geometry, recent models are increasingly based on
      experimentally assessed cellular parameters such as the dynamics of signaling
      processes and the mechanical properties of the cell wall. Recent modeling
      attempts have therefore substantially gained in biological relevance and
      predictive power. Different modeling methods are explained and the power and
      limitations of individual models are compared. Focus is on several recent models
      that use closed feedback loops in order to generate limit cycles representing the
      oscillatory behavior observed in growing tubes.

PMID- 23000433
TI  - Imprinting meets genomics: new insights and new challenges.
AB  - Until recently, only a handful of imprinted genes, or genes with parent-of-origin
      dependent expression patterns, were known in plants. Study of these genes yielded
      key insights into mechanisms of monoallelic expression and imprinted gene
      function. The recent application of high throughput sequencing to the study of
      imprinting has confirmed that many previous findings are relevant on a genome
      wide scale. The catalogue of imprinted genes in monocots and dicots now includes
      a large number of transcription factors, chromatin related genes, and metabolic
      or hormone biosynthesis enzymes. Interpretation of allele specific expression
      data remains a challenge, with careful validation of candidate imprinted genes
      necessary.

PMID- 23000434
TI  - Regulation of apomixis: learning from sexual experience.
AB  - Apomixis is a natural form of asexual reproduction through seeds that leads to
      viable offspring genetically identical to the mother plant. New evidence from
      sexual model species indicates that the regulation of female gametogenesis and
      seed formation is also directed by epigenetic mechanisms that are crucial to
      control events that distinguish sexuality from apomixis, with important
      implications for our understanding of the evolutionary forces that shape
      structural variation and diversity in plant reproduction.

PMID- 23000435
TI  - Liver transplantation for hepatocellular carcinoma in a patient with a novel
      telomerase mutation and steatosis.
AB  - We report the case and discuss the outcome of a 63-year-old man, who was
      transplanted for hepatocellular carcinoma arising from cirrhosis associated with
      non-alcoholic fatty liver and diabetes. Because of co-existent well-compensated
      idiopathic familial pulmonary fibrosis and family history of cryptogenic
      cirrhosis, he was screened and found positive for a novel c.2062 C>G telomerase
      (TERT) mutation, encoding for the protein Glu668Asp variant, which was also
      confirmed in the neoplastic tissue. TERT mutations have very recently been
      associated with a spectrum of familial hepatic liver diseases often characterized
      by steatosis and hepatic iron overload, and have been reported to represent a
      frequent risk factor for cirrhosis, being observed in as much as 3-8% of
      unselected patients with different liver diseases. Due to the systemic
      involvement of telomerase diseases very likely influencing the clinical outcome,
      and the peculiar biological features of hepatocellular carcinoma arising in this
      context, we suggest that patients with cryptogenic cirrhosis or other suggestive
      features should be screened for TERT mutations and specific treatment algorithms
      elaborated for this disease.

PMID- 23000436
TI  - Focus.

PMID- 23000437
TI  - The human gastrointestinal microbiota--an unexplored frontier for pharmaceutical
      discovery.
AB  - The mammalian gastrointestinal tract (GIT) harbors microorganisms (the
      microbiota) of vast phylogentic, genomic, and metabolic diversity, and recent
      years have seen a rapid development in the techniques for studying these complex
      microbial ecosystems. It is increasingly apparent that the GIT microbiota plays
      an intricate role in host health and disease. Targeted strategies for modulating
      human health through the modification of the GIT microbiota, however, are
      developing and in their infancy. This perspective article discusses the
      rationale, benefits and limitations of using the GIT microbiota as a
      pharmacological and nutritional target in the treatment of various diseases and
      disorders linked to imbalances in our microbiota.

PMID- 23000438
TI  - Percutaneous left atrial appendage closure in awake non intubated patient:
      Multimodality intraprocedural imaging.
AB  - We present a case of percutaneous left atrial appendage closure in awake non
      intubated patient, in which Intraprocedural ultrasound images were obtained with
      a micro transesophageal echocardiographic probe (MTEE) and intracardiac
      echocardiography (ICE) together with angiography.

PMID- 23000439
TI  - Kissing drug-eluting balloons for the treatment of unprotected distal left main
      bifurcation drug-eluting stent restenosis.
AB  - The advent of drug-eluting stents (DES) associated with improvements in
      interventional techniques, encouraged the use of percutaneous coronary
      intervention (PCI) for unprotected left main (ULM) stenosis because of the lower
      need of repeat revascularization compared to the bare-metal stents (BMS).
      Nevertheless, ULM DES in-stent restenosis (ISR) continues to occur. The choice of
      treatment strategy (medical treatment, repeated PCI, or coronary artery bypass
      graft) for ULM DES-ISR depends primarily on several clinical and angiographic
      factors, making optimal patient selection crucial in the appropriate treatment of
      ULM-ISR lesions and achievement of favorable long-term outcomes. We describe in
      this report a successful modern approach to manage a distal ULM DES-ISR following
      a 2-stent strategy, consisting in the kissing inflation of two DEBs in both
      branches of the bifurcation.

PMID- 23000440
TI  - Tobacco control: economic aspects of smoking.

PMID- 23000441
TI  - Mammography rates after the 2009 US Preventive Services Task Force breast cancer
      screening recommendation.
AB  - OBJECTIVE: To measure the impact of the 2009 US Preventive Services Task Force
      (USPSTF) breast cancer screening recommendation, which recommended against
      routine screening for women aged 40 to 49 and stated that there was "insufficient
      evidence" to recommend screening for women aged 75 and older, on mammography
      rates. METHODS: Self-reported mammography rates were calculated using the 2006
      2010 Medical Expenditure Panel Surveys (n=29,857). The paper reports mammography
      rates by age group (40 to 49, 50 to 74, and 75 and older), adjusted for age,
      race/ethnicity, socioeconomic status, and region. The study was performed at
      Emory University in Atlanta, Georgia, USA in 2012. RESULTS: Differences in
      mammography rates between 2010 and earlier years were not significant. Among
      women aged 40-49, biennial mammography rates declined by -0.5 percentage points
      between 2006 to 2009 and 2010 (95% confidence interval [CI]: -3.0 to 1.9;
      p=0.67). Among women aged 50-74, rates declined by -0.07 percentage points (95%
      CI: -1.8 to 1.7; p=0.93). Among women aged 75 years and older, rates declined by 
      0.1 percentage points (95% CI: -4.2 to 3.9; p=0.94). CONCLUSION: The revision to
      the USPSTF breast cancer screening recommendation did not affect screening
      patterns.

PMID- 23000442
TI  - Selective inhibitory effects of mollugin on CYP1A2 in human liver microsomes.
AB  - Mollugin originally isolated from Rubia cordifolia is a pharmacological compound
      for its anti-inflammation, anti-cancer, and anti-viral activity. In the present
      study, a cocktail probe assay was performed for determination of the selective
      inhibitory effect of mollugin on cytochrome P450 (CYP) enzymes in human liver
      microsomes (HLM). Incubation of isoform-specific substrate probes CYPs with
      mollugin (0-25MUM) in HLM resulted in strong inhibition of CYP1A2-catalyzed
      phenacetin O-deethylation, showing IC(50) values of 1.03 and 3.55MUM without and
      with pre-incubation, respectively. Mollugin-caused inhibition of phenacetin O
      deethylation was concentration-dependent in HLMs, but not time-dependent. In
      addition, the Lineweaver-Burk plot indicated a typical competitive inhibition.
      Inhibitory effects of mollugin on human recombinant cDNA-expressed CYP1A1 and 1A2
      were comparable. Taken together, the results suggested that mollugin might cause
      herb-drug interaction through selective inhibition of CYP1A2 in humans receiving
      herbal medications, including R. cordifolia.

PMID- 23000443
TI  - Low-dose gamma irradiation of food protein increases its allergenicity in a
      chronic oral challenge.
AB  - Few chronic food protein models have described the relationship between
      allergenicity and the molecular structure of food protein after physical
      processing. The effect of gamma-radiation on the structure of food protein was
      measured by fluorescence, circular dichroism and microcalorimetry. BALB/c mice
      were intraperitoneally sensitized and then given non-irradiated and irradiated
      Con-A by daily gavage for 28days. The tendency to form insoluble amorphous
      aggregates and partially unfolded species was observed after irradiation. The
      administration of non-irradiated and irradiated samples at low-dose significantly
      increased weight loss as well as plasma levels of eotaxin in animals repeatedly
      exposed to Con-A. Significant lymphocytic infiltrate filling completely the
      stroma of microvilli and tubular glands was observed in the small intestinal of
      the group given Con-A irradiated at a low dose. This phenotype was not observed
      in animals treated with Con-A irradiated at a high dose.

PMID- 23000444
TI  - A detailed study of developmental immunotoxicity of imidacloprid in Wistar rats.
AB  - Human exposure to imidacloprid is likely to occur during its use as an acaricide
      or an ectoparasiticide. Accordingly, the developmental immunotoxic potential of
      imidacloprid was investigated. Oral exposure was initiated in timed pregnant
      female Wistar rats on gestation day 6 (GD 6) till GD 21. On GD 20, half of the
      gravid dams were sacrificed, and in utero fetal development was assessed. In the
      other half of the dams, administration was continued till weaning on postnatal
      day 21 (PND 21) and maternal toxicity was investigated. A subgroup of weaned pups
      was sacrificed to assess immunotoxicity parameters. The other half of the pups
      were exposed to imidacloprid till PND 42, and immunotoxicity was assessed. The
      findings revealed post-implantation loss in the highest dose group, indicating
      the risk of abortion. Soft tissue abnormalities and skeletal alterations were
      observed in the highest dose group. Humoral immunity was assessed by estimating
      hemagglutination titer and immunoglobulin production. Cell mediated immunity was
      assessed by Delayed Type Hypersensitivity, whereas, non-specific immunity was
      assessed by phagocytic index, and other phenotypic parameters. These data
      revealed that imidacloprid caused age-dependent adverse effects on the developing
      immunity which was aggravated when exposure continued throughout development,
      leading to a compromised immune system.

PMID- 23000445
TI  - Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway.
AB  - Previous studies have demonstrated that wogonoside, a bioactive flavonoid
      extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory
      and anti-angiogenic activities. In this study, we evaluated wogonoside-induced
      autophagy on human breast MDA-MB-231 cells. We report that wogonoside triggered
      the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive
      autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA
      MB-231 cells. In addition, cells treated by wogonoside developed autophagosome
      like characteristics, including single and double membrane vacuoles containing
      intact and degraded cellular debris. The results showed that wogonoside promotes
      the expression of LC3-II and Beclin-1. Furthermore, wogonoside inhibited cell
      growth of MDA-MB-231 cells in a concentration- and time-dependent manner, which
      was associated with wogonoside-induced autophagy. Wogonoside also suppressed the
      activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by
      regulating the expression of the extracellular signal-regulated kinase (ERK1/2)
      and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway. Taken
      together, these results suggest that wogonoside partially inhibits MDA-MB-231
      cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a
      promising anti-tumor agent.

PMID- 23000446
TI  - Water extracts of tree Hypericum sps. protect DNA from oxidative and alkylating
      damage and enhance DNA repair in colon cells.
AB  - Diet may induce colon carcinogenesis through oxidative or alkylating DNA damage.
      However, diet may also contain anticarcinogenic compounds that contribute to
      cancer prevention. DNA damage prevention and/or induction of repair are two
      important mechanisms involved in cancer chemoprevention by dietary compounds.
      Hypericum sps. are widely used in traditional medicine to prepare infusions due
      to their beneficial digestive and neurologic effects. In this study, we
      investigated the potential of water extracts from three Hypericum sps. and some
      of their main phenolic compounds to prevent and repair oxidative and alkylating
      DNA damage in colon cells. The results showed that water extracts of Hypericum
      perforatum, Hypericum androsaemum, Hypericum undulatum, quercetin and rutin have
      protective effect against oxidative DNA damage in HT29 cells. Protective effect
      was also observed against alkylating DNA damage induced by methyl
      methanesulfonate, except for H. androsaemum. With regard to alkylating damage
      repair H. perforatum, H. androsaemum and chlorogenic acid increased repair of
      alkylating DNA damage by base excision repair pathway. No effect was observed on
      nucleotide excision repair pathway. Antigenotoxic effects of Hypericum sps. may
      contribute to colon cancer prevention and the high amount of phenolic compounds
      present in Hypericum sps. play an important role in DNA protective effects.

PMID- 23000447
TI  - A 90-day feeding study of glyphosate-tolerant maize with the G2-aroA gene in
      Sprague-Dawley rats.
AB  - Maize is not only a staple food crop but also an important raw material for feed
      and industry; however, the threat of weeds leads to a serious decline in its
      output and quality. The G2-aroA gene confers glyphosate herbicide tolerance to
      crops. In this study, the food safety of genetically modified (GM), glyphosate
      tolerant maize with the G2-aroA gene was evaluated in a 90-day feeding study in
      Sprague-Dawley (SD) rats. Maize grain from GM or non-GM isogenic control lines
      were separately formulated into rodent diets at concentrations of 12.5% (low
      level), 25% (middle level), and 50% (high level). An additional group of rats
      were fed a commercialized diet as a control. The toxicological response
      variables, including body weights, food consumption, serum biochemistry,
      hematology, and absolute and relative organ weights, were compared between rats
      fed GM maize and those fed non-GM maize after consumption of test diets for
      90days. In addition, gross and microscopic pathology were conducted among
      treatment groups. No adverse effects related to the consumption of GM maize were
      detected in the subchronic feeding study. These results indicated that the GM
      glyphosate-tolerant maize was as safe and nutritious as conventional maize.

PMID- 23000448
TI  - Identification of gene expression profiles in HeLa cells and HepG2 cells infected
      with Coxsackievirus B3.
AB  - Viral infections of host cells cause multiple changes of cellular metabolism
      including immediate defense mechanisms as well as processes to support viral
      replication. Coxsackievirus B3 (CVB3) is a member of the Picornavirus family and
      is responsible for a wide variety of mild or severe infections including acute
      and chronic inflammations. Thereby, intracellular signaling can be changed very
      comprehensively. In order to compare the influence of CVB3 replication on gene
      expression pattern of two different cell lines, DNA microarray systems were used
      to study a set of 780 genes related to inflammation. Expression analysis of HeLa
      cells and HepG2 cells infected with CVB3 identified 34 genes whose mRNA levels
      were altered significantly upon infection. The expression of additional 16 genes
      in HepG2 cells and 31 genes in HeLa cells were found to be influenced during CVB3
      replication as well. All genes expressed differentially were sorted with regard
      to their functions and interpreted in view of known contributors to the infection
      process. The activation of the tumor necrosis factor pathways by CVB3 represents
      one peculiar observation, including apoptosis, stress, and inflammation
      responses.

PMID- 23000450
TI  - -116A and K BCHE gene variants associated with obesity and hypertriglyceridemia
      in adolescents from Southern Brazil.
AB  - Butyrylcholinesterase (BChE) has been associated to body mass index (BMI),
      weight, cholesterol and triglyceride levels. -116A (rs1126680) and K (A539T,
      1615A, rs1803274) BCHE gene variants had previously been associated to BChE
      activity, weight and BMI variance in adults. The present study examined -116A and
      K variants, BChE activity, anthropometric and biochemical variables associated
      with obesity in adolescents (120 obese and 150 non-obese from Curitiba, Brazil).
      Both -116A and K variants were found with significantly lower frequencies
      (p<0.05) in obese adolescents when compared with non-obese adolescents and with
      the general population. Mean BChE activity (KU/L) was significantly higher in
      obese adolescents when compared with non-obese adolescents and with the general
      population. Analyzing only the obese adolescents, it was found that carriers of
      the -116A variant showed lower BChE activity and higher triglyceride levels than
      homozygotes for the usual allele. Indeed, obese carriers of the -116A variant had
      triglyceride levels considered high according to reference values for serum
      triglycerides in Brazilian adolescents. These results show: (1) a protective
      effect of -116A and K variants on juvenile obesity risk, suggesting a role for
      the BCHE gene on juvenile onset obesity different from that observed on adult
      onset obesity and (2) an association of the -116A variant with
      hypertriglyceridemia in obese adolescents probably because of its effect on
      lowering BChE activity and consequently diminishing the enzyme capability of
      maintaining homeostasis on lipid metabolism during the metabolic stress caused by
      obesity.

PMID- 23000449
TI  - Characterization of acetylcholinesterase in Hong Kong oyster (Crassostrea
      hongkongensis) from South China Sea.
AB  - Acetylcholinesterase (AChE) activity has been used to evaluate the exposure of
      mollusk bivalves to organophosphates, carbamate pesticides, and heavy metals.
      Crassostrea hongkongensis is a Hong Kong endemic oyster, and has a high
      commercial value along the coastal area of South China. The use of this species
      as a bio-indicator of the marine environment, and the use of AChE activity
      measurements in tissues of C. hongkongensis require prior characterization of
      AChE in this species. Here, we report that gill tissue contains the highest AChE
      activity in C. hongkongensis, and that the molecular form of AChE is most likely
      to be a dimeric form. In addition, the effect of the pesticide acephate on AChE
      activity in the gill of C. hongkongensis was analyzed, and the mean inhibition
      concentration (IC50) value was determined. This study suggests that AChE activity
      in the gill tissue of C. hongkongensis might be used as a biomarker in monitoring
      organophosphate contamination in the marine fauna of South China.

PMID- 23000451
TI  - Plants as a source of butyrylcholinesterase variants designed for enhanced
      cocaine hydrolase activity.
AB  - Cocaine addiction affects millions of people with disastrous personal and social
      consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and
      even those who undergo rehabilitation and experience long periods of abstinence
      have more than 80% chance of relapse. Yet there is no FDA-approved treatment to
      decrease the likelihood of relapse in rehabilitated addicts. Recent studies,
      however, have demonstrated a promising potential treatment option with the help
      of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking
      down naturally occurring (-)-cocaine before the drug can influence the reward
      centers of the brain or affect other areas of the body. This activity of wild
      type (WT) BChE, however, is relatively low. This prompted the design of variants
      of BChE which exhibit significantly improved catalytic activity against (-)
      cocaine. Plants are a promising means to produce large amounts of these cocaine
      hydrolase variants of BChE, cheaply, safely with no concerns regarding human
      pathogens and functionally equivalent to enzymes derived from other sources.
      Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana
      using the MagnICON virus-assisted transient expression system, and in reporting
      their initial biochemical analysis, we provide proof-of-principle that plants can
      express engineered BChE proteins with desired properties.

PMID- 23000452
TI  - Use of echocardiography to evaluate the cardiac effects of therapies used in
      cancer treatment: what do we know?
AB  - Cardiologists and oncologists today face the daunting challenge of identifying
      patients at risk for late-onset left ventricular (LV) systolic dysfunction from
      the use of various chemotherapeutic agents. Currently, the most widely used
      method in clinical practice for monitoring the potential of chemotherapy-induced
      cardiotoxicity is calculation of LV ejection fraction. The use of LV ejection
      fraction to determine whether to continue or discontinue the use of
      chemotherapeutic agents is limited, because decreases in LV ejection fraction
      frequently occur late and can be irreversible. These limitations have led to the
      exploration of diastolic function and newer modalities that assess myocardial
      mechanics to identify sensitive and specific variables that can predict the
      occurrence of late systolic function. The cancer therapies associated with
      cardiotoxicity are reviewed in this report. Additionally, the authors evaluate
      the role of present-day echocardiographic parameters, complementary noninvasive
      imaging modalities, and biomarkers in the prediction of cardiotoxicity. The
      authors address the evolving role of cardioprotective agents and potential
      therapies to prevent or reverse the progression of LV systolic dysfunction.
      Finally, they provide some ideas regarding future directions to enhance the
      knowledge of predicting late-onset LV systolic dysfunction secondary to cancer
      therapy.

PMID- 23000453
TI  - Differential expression of miRNAs in rhabdomyosarcoma and malignant rhabdoid
      tumor.
AB  - Alveolar rhabdomyosarcoma (RMA) and malignant rhabdoid tumor (MRT) have a
      frequent metastatic spread and a poor prognosis. Aberrant miRNA expression is
      often found in metastatic tumors. The aim of this study was to identify specific
      miRNA expression patterns in these tumors. We analyzed the expression of miRNAs
      in RMA and MRT in tissue samples and in the rhabdomyosarcoma (RMS) cell lines
      (Rh30 and RD). Selected target miRNAs were modulated with mimic or inhibitor
      oligonucleotides. Functional analysis was monitored by flow cytometry and
      migration assays. A set of 107 differentially expressed miRNAs showed tissue
      specific clustering of RMA and MRT. Comparison with the Sarcoma microRNA
      Expression Database revealed RMA- and MRT-specific miRNAs. Metastatic invasion
      associated miRNA miR-9 was overexpressed in RMA. miR-200c-inhibiting migration
      was lower expressed in RMA than in MRT. Transient transfection of RMS cells with
      a miR-200c mimic and miR-9( inhibitor did neither increase the expression of the
      known target E-cadherin nor decrease migration. Expression of E-cadherin could be
      induced in RD cells using decitabine, but demethylation did not influence cell
      migration. Despite a comparable high rate of metastatic invasion pediatric RMA
      and MRT show a different pattern of miRNA expression possibly allowing risk
      stratification.

PMID- 23000454
TI  - Beneficial effects of carbamylated erythropoietin against oxygen-glucose
      deprivation/reperfusion-induced astrocyte swelling: proposed molecular mechanisms
      of action.
AB  - Carbamylated erythropoietin (C-EPO), one of the erythropoietin derivatives,
      retains strong anti-edema and neuroprotective properties while lacking the
      hematopoietic complications of erythropoietin. This study investigated the
      intracellular and molecular mechanisms underlying the anti-edema property of C
      EPO. An in vitro model of astrocyte swelling was created by 5h of oxygen-glucose
      deprivation and subsequent reperfusion (OGD/Rep). Astrocyte cultures were then
      treated with C-EPO or left as control cells. Here we show that increases in
      astrocyte volume, morphological cell swelling, and changes in ultrastructure
      after OGD/Rep were significantly mitigated by treatment with C-EPO (10 ng/ml).
      The decreases in AQP-4 phosphorylation after OGD/Rep were remarkably recovered by
      C-EPO treatment. The OGD/Rep-induced upregulations of AQP-4 mRNA and protein were
      also prevented by C-EPO treatment. Additional treatment with phorbol myristate
      acetate, an activator of protein kinase C (PKC), enhanced C-EPO-mediated
      neuroprotective effects, while that of H-7, an inhibitor of PKC, blocked these
      protections. Our findings establish that C-EPO effectively mitigates astrocyte
      swelling induced by ischemia and reperfusion-like injury. The modulation of AQP-4
      phosphorylation and expression via the PKC pathway is participated in the
      neuroprotective effects of C-EPO.

PMID- 23000455
TI  - P200 can be modulated by orthography alone in reading Chinese words.
AB  - The present study examined the relation between the event-related potential
      component P200 and orthographic processing in reading Chinese words. Participants
      performed a semantic judgment task on pairs of words (prime-target pairs)
      presented sequentially and the P200 elicited by the second target word was
      examined and compared across different prime conditions. The critical pairs were
      single characters similar in orthography but unrelated in phonology or semantics.
      Results showed that for both integrated and composite characters, visually
      similar primes led to reduced P200 than control primes and the effect was larger
      for composite characters than integrated characters. The study presented clear
      evidence that P200 is sensitive to orthographic similarity and can be modulated
      by orthography alone in reading Chinese word.

PMID- 23000456
TI  - Functional status and relationships of melanocortin 1 receptor signaling to the
      cAMP and extracellular signal-regulated protein kinases 1 and 2 pathways in human
      melanoma cells.
AB  - Melanocortin 1 receptor (MC1R), a major determinant of skin phototype frequently
      mutated in melanoma, is a Gs protein-coupled receptor that regulates pigment
      production in melanocytes. MC1R stimulation activates cAMP synthesis and the
      extracellular signal-regulated (ERK) ERK1 and ERK2. In human melanocytes, ERK
      activation by MC1R relies on cAMP-independent transactivation of the c-KIT
      receptor. Thus MC1R functional coupling to the cAMP and ERK pathways may involve
      different structural requirements giving raise to biased effects of skin cancer
      associated mutations. We evaluated the impact of MC1R mutations on ERK
      activation, cAMP production and agonist binding. We found that MC1R mutations
      impair cAMP production much more often than ERK activation, suggesting less
      stringent requirements for functional coupling to the ERK pathway. We examined
      the crosstalk of the cAMP and ERK pathways in HBL human melanoma cells (wild-type
      for MC1R, NRAS and BRAF). ERK activation by constitutively active upstream
      effectors or pharmacological inhibition had little effect on MC1R-stimulated cAMP
      synthesis. High cAMP levels were compatible with normal ERK activation but,
      surprisingly, the adenylyl cyclase activator forskolin abolished ERK activation
      by MC1R, most likely by a cAMP-independent mechanism. These results indicate
      little crosstalk of the cAMP and ERK pathways in HBL melanoma cells. Finally, we
      studied cAMP accumulation in a panel of 22 human melanoma cell lines stimulated
      with MC1R agonists or forskolin. cAMP synthesis was often inhibited, even in
      cells wild-type for MC1R and NRAS. Therefore, the cAMP pathway is more frequently
      impaired in melanoma than could be predicted by the MC1R or NRAS genotype.

PMID- 23000458
TI  - Unintended pregnancy among rural women in Bangladesh.
AB  - Unintended pregnancies are associated with unsafe abortion and greater risk of
      maternal morbidity and maternal deaths. In Bangladesh, approximately one-third of
      pregnancies are unintended. Considering the magnitude of the situation and its
      consequences, this article explores factors associated with the prevalence of
      unintended pregnancies in rural Bangladesh with implications for policy
      intervention. A total of 3300 women were interviewed from 22 sub-districts to
      collect information on unintended pregnancy related issues. Findings reveal that
      about 29% of the pregnancies were unintended and the frequency of unintended
      pregnancy was higher among the older, less educated, higher parity, and poor
      women. Findings also suggest that unintended pregnancy rate was higher (33%)
      among women who used contraceptive before their last pregnancy than women (23%)
      who did not use any contraceptive. The rate of unintended pregnancy also varied,
      by the types of contraceptive methods used before their last pregnancy. The women
      who were using traditional methods or temporary modern methods were more likely
      to experience unintended pregnancy than longer acting method users. The findings
      underscore the importance of measuring contraceptive discontinuation rates in
      addition to prevalence of all modern methods. When discussing policy
      interventions to generate demand for family planning, consideration of
      differences in method-specific discontinuation rates is important if policy
      objectives to reduce unintended pregnancies are to be achieved.

PMID- 23000459
TI  - Reproductive health knowledge, attitude, and behaviors of technical college
      students in Velikye Novgorod, Russia.
AB  - An analysis of five focus groups conducted with students ages 16-20 attending
      technical college in Velikye Novgorod regarding reproductive health issues. The
      results show a high level of sexual activity, but low levels of contraceptive use
      and negative attitudes toward modern contraceptive methods. Despite public
      disapproval of induced abortion, its use appears widespread.

PMID- 23000460
TI  - Reliability of the high school Youth Risk Behavior Survey when administered
      online.
AB  - The Youth Risk Behavior Survey (YRBS) is frequently used by states and local
      school districts for monitoring and assessing health risk behaviors among middle
      and high school youth in the United States. This study assessed the reliability
      of the High School YRBS questions when the survey is administered as a web-based
      survey. A test-retest reliability study was conducted on a sample of high school
      students in grades 9-12. Students self-administered an online version of the high
      school YRBS at two different time periods. Kappa scores were computed for all
      items in order to measure reliability. Items measured prevalence estimates of
      behaviors related to unintentional injuries and violence, tobacco use, alcohol
      and other drug use, and sexual behaviors. The mean kappa reliability score was
      similar to scores obtained in prior reliability studies of the YRBS when
      administered as paper surveys; 87% of the 69 selected items from the 79-item
      paper survey used had kappa scores that indicated moderate or substantial
      reliability. Findings indicate the reliability of the online High School YRBS
      when administered to students online and its potential as an alternative to paper
      survey.

PMID- 23000461
TI  - Identifying barriers and sustainable solution to childhood immunization in Khana
      local government area of Rivers State, Nigeria.
AB  - The aim of this study was to uncover barriers to childhood immunization in order
      to make recommendations that will address the problem in Rivers State and
      Nigeria. A descriptive, cross-sectional study was carried out in September 2008,
      among mothers and caregivers of children aged 0-5 years, to examine the various
      barriers to childhood immunization in the Khana Local Government Area of the
      State. Data was analyzed using Epi Info version 6.4d software. A total of 1560
      mothers and caregivers were interviewed. Their knowledge about immunization was
      low. Only 15.2% was able to define immunization and mention six vaccine
      preventable diseases. Most children (46.8%) did not complete their immunization
      schedule because of frequent shortage of vaccines in the health facilities. Long
      term and advance commitment by the government to vaccine manufacturers to
      purchase vaccines and engaging communities in dialogue over benefits of
      immunization is advocated to improve immunization in the State.

PMID- 23000462
TI  - Factors contributing to participation of a rural community in health education: a
      case study from ethiopia.
AB  - This study investigated factors that contributed to the participation of a rural
      community in health education. It was conducted in the Awi zone of the Amhara
      region in Ethiopia. The participants were rural community members and health
      extension workers. Purposive and snowball sampling techniques were used to
      recruit rural community members, whereas convenient sampling was used to recruit
      health extension workers. Data was collected through in-depth individual
      interviews, and focus group discussions. The study revealed various factors
      contributing to the participation of a rural community in health education,
      including attainability of the objectives of health education, profiles of the
      health extension workers, peer influence, organization of the health education
      program in terms of place and time, and meaningfulness of the health education in
      terms of rural community lives. Although the ultimate goal of participation in
      health education is similar for all rural community members, they were attracted
      to the program by one or more than one different factor. Efforts aimed at
      enhancing participation of a rural community in health education program should
      address each factor that contributes to the participation of community members.

PMID- 23000463
TI  - Pilot training of community mobilizers as health educators to prevent
      onchocerciasis in Bugai, Kaduna State, Nigeria.
AB  - About 33 million Nigerians are at risk of onchocerciasis (river blindness)
      including people in Bugai community where the prevalence is high. This is
      attributed to poor knowledge of preventive measures, so there is a need to
      empower people with health information. This pilot study aimed at training 38
      volunteered community leaders as mobilizers with the intention of using them to
      disseminate health information on prevention of onchocerciasis to the entire
      Bugai community. The intervention study made use of an adapted preventive health
      education manual. Selection was based on interest and influential ability of the
      mobilizers. Pre- and post-test on knowledge of prevention was conducted. Post
      test results showed increased knowledge due to significant effect of the training
      (P = 0.00). Thereafter, the trained community mobilizers disseminated the same
      information to the entire community. Overall result showed that empowering people
      with adequate health information is a good means of preventing onchocerciasis
      where prevalence is high.

PMID- 23000464
TI  - Differentiation and function of the ovarian somatic cells in the pseudoscorpion,
      Chelifer cancroides (Linnaeus, 1761) (Chelicerata: Arachnida: Pseudoscorpionida).
AB  - Pseudoscorpion females carry fertilized eggs and embryos in specialized brood
      sacs, where embryos are fed with a nutritive fluid produced and secreted by
      somatic ovarian cells. We used various microscopic techniques to analyze the
      organization of the somatic cells in the ovary of a pseudoscorpion, Chelifer
      cancroides. In young specimens, the ovary is a cylindrical mass of internally
      located germline cells (oogonia and early previtellogenic oocytes) and two types
      of somatic cells: the epithelial cells of the ovarian wall and the internal
      interstitial cells. In subsequent stages of the ovary development, the oocytes
      grow and protrude from the ovary into the hemocoel (opisthosomal cavity). At the
      same time the interstitial cells differentiate into the follicular cells that
      directly cover the oocyte surface, whereas some epithelial cells of the ovarian
      wall form the oocyte stalks - tubular structures that connect the oocytes with
      the ovarian tube. The follicular cells do not seem to participate in oogenesis.
      In contrast, the cells of the stalk presumably have a dual function. During
      ovulation the stalk cells appear to contribute to the formation of the external
      egg envelope (chorion), while in the post-ovulatory phase of ovary function they
      cooperate with the other cells of the ovarian wall in the production of the
      nutritive fluid for the developing embryos.

PMID- 23000465
TI  - Responses of epidermal cell turgor pressure and photosynthetic activity of leaves
      of the atmospheric epiphyte Tillandsia usneoides (Bromeliaceae) after exposure to
      high humidity.
AB  - It has been well-established that many epiphytic bromeliads of the atmospheric
      type morphology, i.e., with leaf surfaces completely covered by large,
      overlapping, multicellular trichomes, are capable of absorbing water vapor from
      the atmosphere when air humidity increases. It is much less clear, however,
      whether this absorption of water vapor can hydrate the living cells of the leaves
      and, as a consequence, enhance physiological processes in such cells. The goal of
      this research was to determine if the absorption of atmospheric water vapor by
      the atmospheric epiphyte Tillandsia usneoides results in an increase in turgor
      pressure in leaf epidermal cells that subtend the large trichomes, and, by using
      chlorophyll fluorescence techniques, to determine if the absorption of
      atmospheric water vapor by leaves of this epiphyte results in increased
      photosynthetic activity. Results of measurements on living cells of attached
      leaves of this epiphytic bromeliad, using a pressure probe and of whole-shoot
      fluorescence imaging analyses clearly illustrated that the turgor pressure of
      leaf epidermal cells did not increase, and the photosynthetic activity of leaves
      did not increase, following exposure of the leaves to high humidity air. These
      results experimentally demonstrate, for the first time, that the absorption of
      water vapor following increases in atmospheric humidity in atmospheric epiphytic
      bromeliads is mostly likely a physical phenomenon resulting from hydration of non
      living leaf structures, e.g., trichomes, and has no physiological significance
      for the plant's living tissues.

PMID- 23000466
TI  - Ectopic expression of an apple apomixis-related gene MhFIE induces co-suppression
      and results in abnormal vegetative and reproductive development in tomato.
AB  - It has been well documented that FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) plays
      important regulatory roles in diverse developmental processes in model plant
      Arabidopsis thaliana. However, it is largely unknown how FIE genes function in
      economically important crops. In this study, MhFIE gene, which was previously
      isolated from apomictic tea crabapple (Malus hupehensis Redh. var. pingyiensis),
      was introduced into tomato. The hemizygous transgenic tomato lines produced curly
      leaves and decreased in seed germination. In addition, the co-suppression of the
      transgenic MhFIE and endogenous (SlFIE) genes occurred in homozygous transgenic
      tomatoes. As a result, FIE silencing brought about abnormal phenotypes during
      reproductive development in tomato, such as increased sepal and petal numbers in
      flower, a fused ovule and pistil and parthenocarpic fruit formation. A yeast two
      hybrid assay and bimolecular fluorescence complementation (BiFC) demonstrated
      that MhFIE interacted with a tomato protein, EZ2 (SlEZ2). Its ectopic expression
      and SlFIE co-suppression notably influenced the expression of genes associated
      with leaf, flower, and fruit development. Therefore, together with other PcG
      proteins, FIE was involved in the regulation of vegetative and reproductive
      development by modulating the expression of related genes in plants.

PMID- 23000467
TI  - Screening of prevailing processes that drive surface water quality of running
      waters in a cultivated wetland region of Germany - a multivariate approach.
AB  - The Spreewald wetland is a large, peaty, inland delta wetland in which the water
      level is managed by weirs in cascade belts across an extensive, partly
      channelized running water system. To model the quality of the water, 946 surface
      water samples from 43 sites were analyzed for 29 water quality parameters in two
      monitoring programs spanning a period of six years. In this study, we pursued a
      multivariate approach using nonlinear principal component analysis (Isomap) to
      identify the prevailing processes that control the water quality of the complex
      surface water system. The first four principal components explained 79% of the
      variance in the dataset. These components were interpreted as anthropogenic
      impact factors, such as groundwater exfiltration from degraded peat areas and the
      influence of coal mining drainage with respect to SO(4), as well as groundwater
      exfiltration from mineral aquifers, and phytoplankton growth and competition. A
      sub-area of the Spreewald wetland, characterized by a sandy aquifer overlain by
      degraded peat, had the greatest impact on downstream surface water quality for
      most of the investigated parameters. In order to achieve better water quality in
      the Spreewald wetland, pollutant input - particularly SO(4) input from the
      tributaries - must be controlled by enhancing the wetland's buffer capacity in
      the catchment, and peat mineralization and groundwater exfiltration must be
      minimized by raising the water table of the peatland area and receiving waters.
      The results show that Isomap is a very powerful tool for gaining a better insight
      into the dominating processes defining the surface water quality of complex
      wetland systems. Nevertheless, to be able to draw the right conclusions from
      multivariate statistical approaches such as Isomap it is necessary to possess
      basic knowledge of the structure of the system and of the processes that may
      occur.

PMID- 23000469
TI  - Editor's perspectives--October 2012.

PMID- 23000468
TI  - Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and non-ortho
      PCBs in eggs of white-tailed sea eagles collected along the Swedish coast in the
      Baltic Sea.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated
      dibenzofurans (PCDF), and dioxin-like non-ortho-PCBs were measured in white
      tailed sea eagle (WTSE) eagle eggs collected along the Swedish coast of the
      Baltic Sea during the period 1992-2004. The eggs represent two different
      subpopulations with significantly different nestling brood sizes; the Baltic
      Proper (BP) with an approximately normal nestling brood size (1.62), and the
      south Bothnian Sea (sBS) with reduced nestling brood size (1.22) combined with a
      significantly higher rate of dead eggs. The aim was to investigate if this
      difference in reproductive outcome was linked to differences in exposure to
      dioxin-like compounds. Three eggs collected in Greenland in 2000 were included in
      the study to provide a reference sea eagle population outside of the Baltic Sea
      region. The concentrations of ?PCDD, ?PCDF and ?non-ortho-PCB in the two
      subpopulations from the Baltic Sea (BS) region ranged from 0.41-4.1, 1.2-5.3 and
      180-970 ng/g lipids, respectively, while in the Greenland population the ranges
      were 0.11-0.16, 0.22-0.33 and 57-83 ng/g lipid, respectively. 2,3,4,7,8-PCDF was
      the predominant congener in all areas and accounted for on average 31-49% of the
      total ?PCDD/F concentrations. The total toxic equivalents (TEQ) in sBS WTSEs were
      higher (approximately 39 ng TEQ/g lipid) than reported in eggs for many other
      birds, and the major contributors to the TEQ in the Baltic Sea were the non-ortho
      PCBs. A principal component analysis (PCA) showed a difference in congener
      pattern between the two Baltic regions that was statistically significant
      (Hotelling's T(2) test). We found no significant differences in the total TEQ
      between the two populations (sBS-BP) and thus no evidence was found linking the
      reproductive impairment in WTSE in sBS to the concentrations of PCDD/Fs or non
      ortho-PCBs in the eggs.

PMID- 23000470
TI  - Estimated erosive potential depends on exposure time.
AB  - OBJECTIVES: Evaluate erosive potential of beverages, using exposure times from 3
      to 30 min, and to analyse the relationship between erosion and several drink
      parameters. METHODS: pH, calcium, phosphate and fluoride concentration,
      saturation, titratable-acidity to pH 5.5 and the viscosity of sixteen beverages
      were measured or calculated. Enamel samples (N = 90) were serially exposed to 1
      ml of the beverages for 3, 6, 9, 15 and 30 min and erosion was measured as the
      loss of calcium to the beverage. Rate of erosion per min was calculated by linear
      curve fitting using all exposure times. Linear regression analysis was performed
      to determine the correlation between erosion and the drink parameters. A limited
      multivariate analysis was performed for the outcome parameter with the highest
      univariate correlations (erosion per minute) and 4 drink variables. RESULTS: A
      negative relationship was observed only for pH for all exposure times. Only for
      erosion per min a significant relationship with pH and saturation was found. In a
      model for erosion per min using only saturation, fluoride concentration,
      titratable acidity and viscosity, both saturation and viscosity were shown to
      have a significant effect (p = 0.01 and p = 0.05, respectively). CONCLUSION:
      Exposure times between 3 and 30 min result in very different estimates of erosive
      potential. There is no sound theoretical ground for preferring one or other
      exposure time/outcome as being more clinically relevant. CLINICAL RELEVANCE: This
      study shows that effect of the choice of study methodology on the measurement of
      erosive potential of beverages is large.

PMID- 23000471
TI  - Effect of waiting interval on chemical activation mode of dual-cure one-step self
      etching adhesives on bonding to root canal dentin.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of waiting
      interval on the chemical activation of dual-cure one-step self-etching adhesives
      before placing resin core materials on the regional bond strength to root canal
      dentin. MATERIALS AND METHODS: Forty-eight post spaces prepared in human lower
      premolars were applied with four dual-cure one-step self-etching adhesives
      Estelite Core Quick: ECB/ECQ, Clearfil DC Core Automix: CDB/CDC, Unifil Core EM:
      UNB/UNC, BeautiCore: BTB/BTC as the manufacturers' instructions. These adhesives
      were cured with light activation for 10 s, or chemical activation with 0, 10, and
      30 s waiting intervals prior to placing resin core material. Resin core materials
      were then placed into the post space and light-cured for 60 s. After 24h water
      storage, each specimen was serially sliced into 8, 0.6 mm * 0.6 mm thick beams
      for the MUTBS test. The regional MUTBS data were analyzed using three-way ANOVA
      and Dunnett's T3 test (p < 0.05). RESULTS: For the chemical activation with 10
      and 30 s waiting intervals, ECB and CDB exhibited significantly improved MUTBS,
      whereas for UNB and BTB, the MUTBS were not significantly different but increased
      with waiting interval. On the other hand, light-activation of all the adhesives
      produced significantly higher MUTBS to root canal dentin than chemical activation
      (p < 0.05), except for the UNB group. CONCLUSIONS: For the chemical activation of
      dual-cure one-step self-etching adhesives, a waiting interval prior to placing
      resin core material improved MUTBS to root canal dentin. Polymerising the
      adhesives before polymerisation reaction of resin core material would be
      effective for bonding to root canal dentin. CLINICAL RELEVANCE: For chemical
      activation mode as well as light activation mode, pre-curing of adhesive layer
      before proceeding polymerisation of resin filling material would produce higher
      bonding performance to dentin in the cavity.

PMID- 23000472
TI  - Recent progress in studies of metallic nickel and nickel-based nanoparticles'
      genotoxicity and carcinogenicity.
AB  - Recently, nanoparticles have been the focus of many research and innovation.
      Metallic nickel and nickel-based nanoparticles are among those being exploited.
      Nickel fine particles are known to be genotoxic and carcinogenic. It has been
      discovered that many properties of nano sized elements and materials are not
      present in their bulk states. The nano size of these particles renders them the
      ability to be easily transported into biological systems, thus raising the
      question of their effects on the susceptible system. Therefore scientific
      research on the effects of nickel nanoparticles is important. This mini-review
      intends to summarize the current knowledge on the genotoxicity and
      carcinogenicity potential of metallic nickel and nickel-based nanoparticles
      implicated in in vitro and in vivo mammalian studies.

PMID- 23000473
TI  - Mycobacterium tuberculosis surface protein Rv0227c contains high activity binding
      peptides which inhibit cell invasion.
AB  - Mycobacterium tuberculosis surface proteins involved in target cell invasion may
      be identified as a strategy for developing subunit-based, chemically-synthesized
      vaccines. The Rv0227c protein was thus selected to assess its role in the
      invasion and infection of Mycobacterium tuberculosis target cells. Results
      revealed Rv0227c localization on mycobacterial surface by immunoelectron
      microscopy and Western blot. Receptor-ligand assays using 20-mer, non-overlapping
      peptides covering the complete Rv0227c protein sequence revealed three high
      activity binding peptides for U937 phagocytic cells and seven for A549 cells.
      Peptide 16944 significantly inhibited mycobacterial entry to both cell lines
      while 16943 and 16949 only managed to inhibit entrance to U937 cells and 16951 to
      A549 cells. The Jnet bioinformatics tool predicted secondary structure elements
      for the complete protein, agreeing with elements determined for such chemically
      synthesized peptides. It was thus concluded that high activity binding peptides
      which were able to inhibit mycobacterial entry to target cells are of great
      importance when selecting peptide candidates for inclusion in an anti
      tuberculosis vaccine.

PMID- 23000474
TI  - Nullomer derived anticancer peptides (NulloPs): differential lethal effects on
      normal and cancer cells in vitro.
AB  - We demonstrate the first use of the nullomer (absent sequences) approach to drug
      discovery and development. Nullomers are the shortest absent sequences determined
      in a species, or group of species. By identifying the shortest absent peptide
      sequences from the NCBI databases, we screened several potential anti-cancer
      peptides. In order to improve cell penetration and solubility we added short poly
      arginine tails (5Rs), and initially solubilized the peptides in 1M trehalose. The
      results for one of the absent sequences 9R (RRRRRNWMWC), and its scrambled
      version 9S1R (RRRRRWCMNW) are reported here. We refer to these peptides derived
      from nullomers as PolyArgNulloPs. A control PolyArgNulloP, 124R (RRRRRWFMHW), was
      also included. The lethal effects of 9R and 9S1R are mediated by mitochondrial
      impairment as demonstrated by increased ROS production, ATP depletion, cell
      growth inhibition, and ultimately cell death. These effects increase over time
      for cancer cells with a concomitant drop in IC-50 for breast and prostate cancer
      cells. This is in sharp contrast to the effects in normal cells, which show a
      decreased sensitivity to the NulloPs over time.

PMID- 23000475
TI  - Antimicrobial activity of human beta-defensin 4 analogs: insights into the role
      of disulfide linkages in modulating activity.
AB  - Human beta-defensins (HBDs) are cationic antimicrobial peptides that are
      components of the innate immune system. They are characterized by three disulfide
      bridges. However, the number of cationic residues as well as the presence of
      lysine and arginine residues vary. In HBD4, the cationic residues occur
      predominantly in the N-terminal segment, unlike in HBD1-3. We have examined the
      antimicrobial activity of peptides spanning the N- and C-terminal segments of
      HBD4. We have introduced one, two and three disulfide bridges in the peptides
      corresponding to the N-terminal segments. Peptides corresponding to the N
      terminal segment had identical sequences and variation was only in the number and
      spacing of cysteines and disulfide bridges. Antimicrobial activity to varying
      extents was observed for all the peptides. When two disulfide bridges were
      present, decrease in antimicrobial potency as well as sensitivity of activity to
      salt was observed. Enhanced antimicrobial activity was observed when three
      disulfide bridges were present. The antimicrobial potency was similar to HBD4
      except against Escherichia coli and was attenuated in the presence of salt. While
      the presence of three disulfide bridges did not constrain the peptide to a rigid
      beta-sheet, the activity was considerably more as compared to the peptides with
      one or two disulfide bridges. The peptides enter bacterial and fungal cells
      rapidly without membrane permeabilization and appear to exert their activity
      inside the cells rather than at the membrane.

PMID- 23000476
TI  - Molecular cloning of two distinct precursor genes of NdWFamide, a d-tryptophan
      containing neuropeptide of the sea hare, Aplysia kurodai.
AB  - NdWFamide (NdWFa) is a D-tryptophan-containing cardioexcitatory neuropeptide in
      gastropod mollusks, such as Aplysia kurodai and Lymanea stagnalis. In this study,
      we have cloned two cDNA encoding distinct precursors for NdWFa from the abdominal
      ganglion of A. kurodai. One of the predicted precursor proteins consisted of 90
      amino acids (NWF90), and the other consisted of 87 amino acids (NWF87). Both of
      the predicted precursor proteins have one NWFGKR sequence preceded by the N
      terminal signal peptide. Sequential double staining by in situ hybridization
      (ISH) and immunostaining with anti-NdWFa antibody suggested that NdWFa-precursor
      and NdWFa peptide co-exist in neurons located in the right-upper quadrant region
      of the abdominal ganglion. In ISH, NWF90-specific signal and NWF87-specific one
      were found in different subsets of neurons in the abdominal ganglia of Aplysia.
      The expression level of NWF90 gene estimated by RT-PCR is much higher than that
      of NWF87 gene. These results suggest that NWF90 precursor is the major source of
      NdWFa in Aplysia ganglia.

PMID- 23000477
TI  - A neural network based ensemble approach for improving the accuracy of
      meteorological fields used for regional air quality modeling.
AB  - A neural network based ensemble methodology was presented in this study to
      improve the accuracy of meteorological input fields for regional air quality
      modeling. Through nonlinear integration of simulation results from two
      meteorological models (MM5 and WRF), the ensemble approach focused on the
      optimization of meteorological variable values (temperature, surface air
      pressure, and wind field) in the vertical layer near ground. To illustrate the
      proposed approach, a case study in northern China during two selected air
      pollution events, in 2006, was conducted. The performances of the MM5, the WRF,
      and the ensemble approach were assessed using different statistical measures. The
      results indicated that the ensemble approach had a higher simulation accuracy
      than the MM5 and the WRF model. Performance was improved by more than 12.9% for
      temperature, 18.7% for surface air pressure field, and 17.7% for wind field. The
      atmospheric PM(10) concentrations in the study region were also simulated by
      coupling the air quality model CMAQ with the MM5 model, the WRF model, and the
      ensemble model. It was found that the modeling accuracy of the ensemble-CMAQ
      model was improved by more than 7.0% and 17.8% when compared to the MM5-CMAQ and
      the WRF-CMAQ models, respectively. The proposed neural network based
      meteorological modeling approach holds great potential for improving the
      performance of regional air quality modeling.

PMID- 23000478
TI  - A method for assessing the physical recovery of Antarctic desert pavements
      following human-induced disturbances: a case study in the Ross Sea region of
      Antarctica.
AB  - With increasing visitor numbers an understanding of the impacts of human
      activities in Antarctic terrestrial environments has become important. The
      objective of this study was to develop a means for assessing recovery of the
      ground surface desert pavement following physical disturbance. A set of 11
      criteria were identified to assess desert pavement recovery. Assessed criteria
      were: embeddedness of surface clasts; impressions of removed clasts; degree of
      clast surface weathering; % overturned clasts; salt on underside of clasts;
      development of salt coatings; armouring per m(2); colour contrast; evidence of
      subsidence/melt out; accumulation of salt on cut surfaces; and evidence of
      patterned ground development. Recovery criteria were assigned a severity/extent
      rating on a scale from zero to four, zero being highly disturbed, and four being
      undisturbed. A relative % recovery for each criteria was calculated for each site
      by comparison with a nearby undisturbed control area, and an overall Mean
      Recovery Index (MRI) was assigned to each pavement surface. To test the method,
      54 sites in the Ross Sea region of Antarctica were investigated including areas
      disturbed by: bulldozer scraping for road-fill, contouring for infrastructure,
      geotechnical investigations, and experimental treading trial sites. Disturbances
      had occurred at timescales ranging from one week to 50 years prior to assessment.
      The extent of desert pavement recovery at the sites investigated in this study
      was higher than anticipated. Fifty of the 54 sites investigated were in an
      intermediate, or higher, stage of desert pavement recovery, 30 sites were in an
      advanced stage of recovery, and four sites were indistinguishable from adjacent
      control sites (MRI = 100%). It was found that active surfaces, such as the gravel
      beach deposits at the Greenpeace World Park Base site at Cape Evans, the aeolian
      sand deposits at Bull Pass, and the alluvial fan deposits of the Loop Moraine
      field campsite, recovered relatively quickly, whereas less active sites, such as
      the bulldozed tracks at Marble Point, and Williams Field to McMurdo Station
      pipeline site on Ross Island, showed only intermediate recovery 20-30 years after
      disturbance. The slabby grano-diorite surface material at the former Vanda
      Station site, meant that the impacts that had occurred were hard to detect
      following decommissioning of the station and site remediation. Desert pavements
      disturbed by randomly dispersed footprints, temporary field campsites at the Loop
      Moraine and VXE6 Pond in the Wright Valley, recovered to be undetectable (MRI =
      100%) within five years, whereas track formation from repeated trampling,
      particularly the concentration of larger clasts along the margin of a confined
      track, persisted for over 15 years (MRI = 82%). The recovery assessment method
      developed in this study has environmental management applications and potential
      to advance our ability to predict the recovery of desert pavement following human
      impacts from activities in Antarctica.

PMID- 23000479
TI  - Assertion modeling and its role in clinical phenotype identification.
AB  - This paper describes an approach to assertion classification and an empirical
      study on the impact this task has on phenotype identification, a real world
      application in the clinical domain. The task of assertion classification is to
      assign to each medical concept mentioned in a clinical report (e.g., pneumonia,
      chest pain) a specific assertion category (e.g., present, absent, and possible).
      To improve the classification of medical assertions, we propose several new
      features that capture the semantic properties of special cue words highly
      indicative of a specific assertion category. The results obtained outperform the
      current state-of-the-art results for this task. Furthermore, we confirm the
      intuition that assertion classification contributes in significantly improving
      the results of phenotype identification from free-text clinical records.

PMID- 23000480
TI  - Fixing the breaks in intestinal stem cells after radiation: a matter of DNA
      damage and death or DNA repair and regeneration.

PMID- 23000481
TI  - Declined organ offers in liver transplantation: careful timing or missed
      opportunity?

PMID- 23000484
TI  - Staphylococcus aureus exhibit similarities in their interactions with
      Acanthamoeba and ThP1 macrophage-like cells.
AB  - Staphylococcus aureus is a leading cause of nosocomial infections. Haematogenous
      spread is a pre-requisite but it is not clear how S. aureus survive the onslaught
      of macrophages. Acanthamoeba is a protozoan pathogen that is remarkably similar
      to macrophages, particularly in their cellular structure (morphological and ultra
      structural features), molecular motility, biochemical physiology, ability to
      capture prey by phagocytosis and interactions with microbial pathogens. Thus, we
      hypothesize that S. aureus exhibit similarities in their interactions with
      Acanthamoeba and ThP1 macrophage-like cells. Here, we studied interactions of
      methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA)
      and Staphylococcus epidermidis (SE) with Acanthamoeba castellanii belonging to
      the T4 genotype and macrophage-like cells (ThP1). The findings revealed that both
      MRSA and MSSA exhibited similarities in their binding/association and invasion of
      A. castellanii and ThP1 cells. Long-term incubation showed that MRSA and MSSA can
      survive intracellularly of both Acanthamoeba and ThP1 cells. Overall, these
      findings suggest that Acanthamoeba exhibit similar characteristics with ThP1
      macrophage-like cells in their interaction with MRSA and MSSA. Additionally it
      was shown that bacteria survive inside Acanthamoeba during the encystment process
      as evidenced by bacterial recovery from mature cysts. Given that Acanthamoeba
      cysts are airborne, these findings suggest that cysts may act as "Trojan horse"
      to help spread MRSA to susceptible hosts.

PMID- 23000482
TI  - RNA polymerase II transcription: structure and mechanism.
AB  - A minimal RNA polymerase II (pol II) transcription system comprises the
      polymerase and five general transcription factors (GTFs) TFIIB, -D, -E, -F, and 
      H. The addition of Mediator enables a response to regulatory factors. The GTFs
      are required for promoter recognition and the initiation of transcription.
      Following initiation, pol II alone is capable of RNA transcript elongation and of
      proofreading. Structural studies reviewed here reveal roles of GTFs in the
      initiation process and shed light on the transcription elongation mechanism. This
      article is part of a Special Issue entitled: RNA Polymerase II Transcript
      Elongation.

PMID- 23000483
TI  - Suspected leukemia oncoproteins CREB1 and LYL1 regulate Op18/STMN1 expression.
AB  - Stathmin (STMN1) is a microtubule destabilizing protein with a key role in cell
      cycle progression and cell migration that is up-regulated in several cancers and
      may contribute to the malignant phenotype. However, the factors that regulate its
      expression are not well understood. Loss as well as gain-of-function p53
      mutations up-regulate STMN1 and in acute myelogenous leukemia where p53 is
      predominantly wild-type, STMN1 is also over-expressed. Here we show regulatory
      control of STMN1 expression by the leucine zipper transcription factor (TF) CREB1
      and the basic helix-loop-helix TF LYL1. By ChIP-chip experiments we demonstrate
      in vivo the presence of LYL1 and CREB1 in close proximity on the STMN1 promoter
      and using promoter assays we reveal co-regulation of STMN1 by CREB1 and LYL1. By
      contrast, TAL1, another suspected oncoprotein in leukemia and close relative of
      LYL1, exerts no regulatory effect on the STMN1 promoter. NLI, LMO2 and GATA2 are
      previously described co-activators of Tal1/Lyl1-E47 transcriptional complexes and
      potentiate Lyl1 activation of the STMN1 promoter while having no effect on TAL1
      transactivation. Promoter mutations that abrogate CREB1 proximal binding or
      mutations of the DNA-binding domain of CREB1 abolish LYL1 transcriptional
      activation. These results show that CRE and Ebox sites function as coordinated
      units and support previous evidence of joint CREB1-and LYL1 transcription events
      activating an aberrant subset of promoters in leukemia. CREB1 or LYL1 shRNA knock
      down down-regulate STMN1 expression. Because down-regulation of STMN1 has been
      shown to have anti-proliferative effects, while CREB1 and LYL1 are suspected
      oncoproteins, interference with CREB1-LYL1 interactions may complement standard
      chemotherapy and yield additional beneficial effects.

PMID- 23000485
TI  - New naphthoquinones and an alkaloid with in vitro activity against Toxoplasma
      gondii RH and EGS strains.
AB  - The efficacy of three amino-terpenyl naphthoquinones and the alkaloid liriodenine
      were examined against tachyzoites and tissues cysts of the RH and EGS strains,
      respectively. Monolayers of 2C4 fibroblasts infected with tachyzoites of the RH
      strain were incubated with different concentrations of the compounds for 48 h.
      Specifically, 7-(4-methyl-3-pentenyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-5),
      6-(4-methyl-3-pentenyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-6), 6-(4
      methylpentyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-11), and 8 h-benzo[g]-1,3
      benzodioxolo[6,5,4-de]quinolin-8-one,9Cl-1,2-methylene dioxiaporfina
      (liriodenine) inhibited intracellular replication of T. gondii. The IC(50) values
      obtained for compounds QUI-5 and QUI-6 were 69.35 and 172.81 MUM (i.e., 21.4 and
      53.4 MUg/mL), respectively. The naphthoquinone QUI-11 and liriodenine
      significantly inhibited intracellular replication of T. gondii. The IC(50) values
      obtained with these experiments were 0.32 and 0.07 MUM (i.e., 0.1 and 0.02
      MUg/mL), respectively. Compounds QUI-5, QUI-6, QUI-11 and liriodenine
      demonstrated lower toxicity for 2C4 fibroblasts compared to atovaquone. In
      addition, cysts isolated from the brains of mice chronically infected with the
      EGS strain were exposed to the compounds. Infectivity of the cysts after
      incubation with the compounds was assessed by infection of mice. The data
      obtained showed that in vitro incubation with QUI-6, QUI-11 and liriodenine
      inhibited the infectivity of the bradyzoites. This activity was time- and
      concentration-dependent.

PMID- 23000486
TI  - Best practices for use of the HEMOX analyzer in the clinical laboratory: quality
      control determination and choice of anticoagulant.
AB  - The HEMOX Analyzer (TCS Scientific) has been used to measure the full oxygen
      dissociation curve (ODC) and to calculate P(50) and the Hill coefficient. The
      effects of different anticoagulants on sample stability and P(50) values have not
      been evaluated extensively for this instrument. We characterized an artificial
      hemoglobin (Equil QC463) for quality control (QC) and compared P(50) values for
      blood samples drawn into 3 different anticoagulants (acid citrate dextrose [ACD],
      heparin, and EDTA). P(50) values were not stable in ACD but were stable in
      heparin and EDTA anticoagulants for up to 4 days. Tests with Equil QC463 showed
      that P(50) values were quite sensitive to small variations in buffer pH. Use of
      the correct anticoagulant and strict control of buffer pH are 2 parameters that
      need to be accounted for in best-practices use of this hemoximeter and before
      determining P(50).

PMID- 23000487
TI  - Practical purification of hydrophilic fragments and lead/drug-like molecules by
      reverse phase flash chromatography: tips, tricks and contemporary developments.
AB  - Practical purifications of hydrophilic fragments and lead/drug-like molecules are
      reviewed, focussing particularly on the rational use of C-18 reverse phase flash
      chromatography by exploiting the relationship between retention time and
      distribution coefficients. Logical process changes have been implemented to suit
      the particular physical properties of individual molecules, notably, various
      combinations of dry loading, methanol-buffer gradients, pH control and columns
      designed for 100% aqueous elution. These have been used to great effect;
      facilitating effective, predictable and scalable purifications of fragments and
      lead/drug-like molecules, for which other techniques sometimes fail.

PMID- 23000488
TI  - [A new clinical entity: ascending solar iris degeneration. Report of 284 cases].
AB  - The observation in a certain number of subjects of an atypical iris
      depigmentation led us to study this phenomenon. Therefore, the authors engaged in
      a prospective study of 398 subjects (100 cases in the city of Marrakesh, and 298
      in the city of Dakhla). The geography, clinical signs and environmental factors
      were studied. Depigmentation was observed in 55% of the population of Marrakesh
      and 77% of the population of Dakhla. It is bilateral, symmetric, very
      progressive, always begins in the inferior one-third of the iris, and always
      spares the superior iris covered by the eyelid. By the time the depigmentation
      reaches the middle one-third, the inferior one-third also begins to demonstrate
      stromal atrophy: (26 cases). Of the 45 subjects with normal iris pigmentation, 31
      cases spend more than 8 hours per day in the shade, and 26 cases constantly use
      some means of solar protection (sunglasses, caps, "Taraza", "Feroual"). Thus,
      this acquired iris depigmentation of an ascending nature, accompanied by an
      advanced stage involving primarily inferior iris atrophy, appears to be closely
      associated with exposure to the sun. Ascending solar iris degeneration, if we may
      refer to it as such, is a clinical entity never before reported in the
      literature. Now that we are faced with this new condition, numerous questions
      arise, to which future research must respond. Are there other factors in addition
      to sun exposure, which may lead to the depigmentation? Does this condition lead
      to further ocular pathology (due to the depigmentation and stromal atrophy)? Must
      solar protection be prescribed systematically for anyone at risk?

PMID- 23000489
TI  - "Systematic Reviews and Meta-analyses" in Clinical Gastroenterology and
      Hepatology.

PMID- 23000490
TI  - Characterization of ecto-ATPase activity in the surface of LLC-PK1 cells and its
      modulation by ischemic conditions.
AB  - BACKGROUND: The concentration of extracellular nucleotides is regulated by
      enzymes that have their catalytic site facing the extracellular space, the so
      called ecto-enzymes. METHODS: We used LLC-PK1 cells, a well-characterized porcine
      renal proximal tubule cell line, to biochemically characterize ecto-ATPase
      activity in the luminal surface. The [gamma-(32)P]Pi released after reaction was
      measured in aliquots of the supernatant by liquid scintillation. RESULTS: This
      activity was linear with time up to 20min of reaction and stimulated by divalent
      metals. The ecto-ATPase activity measured in the presence of 5mM MgCl(2) was (1)
      optimum at pH 8, (2) insensitive to different inhibitors of intracellular
      ATPases, (3) inhibited by 1mM suramin, an inhibitor of ecto-ATPases, (4)
      sensitive to high concentrations of sodium azide (NaN(3)) and (5) also able to
      hydrolyze ADP in the extracellular medium. The ATP:ADP hydrolysis ratio
      calculated was 4:1. The ecto-ADPase activity was also inhibited by suramin and
      NaN(3). The dose-response of ATP revealed a hyperbolic profile with maximal
      velocity of 25.2+/-1.2nmol Pixmg(-1)xmin(-1) and K(0.5) of 0.07+/-0.01mM. When
      cells were submitted to ischemia, the E-NTPDase activity was reduced with time,
      achieving 71% inhibition at 60min of ischemia. CONCLUSION: Our results suggest
      that the ecto-ATPase activity of LLC-PK1 cells has the characteristics of a type
      3 E-NTPDase which is inhibited by ischemia. GENERAL SIGNIFICANCE: This could
      represent an important pathophysiologic mechanism that explains the increase in
      ATP concentration in the extracellular milieu in the proximal tubule during
      ischemia.

PMID- 23000491
TI  - Sleep deprivation impairs calcium signaling in mouse splenocytes and leads to a
      decreased immune response.
AB  - BACKGROUND: Sleep is a physiological event that directly influences health by
      affecting the immune system, in which calcium (Ca(2+)) plays a critical signaling
      role. We performed live cell measurements of cytosolic Ca(2+) mobilization to
      understand the changes in Ca(2+) signaling that occur in splenic immune cells
      after various periods of sleep deprivation (SD). METHODS: Adult male mice were
      subjected to sleep deprivation by platform technique for different periods (from
      12 to 72h) and Ca(2+) intracellular fluctuations were evaluated in splenocytes by
      confocal microscopy. We also performed spleen cell evaluation by flow cytometry
      and analyzed intracellular Ca(2+) mobilization in endoplasmic reticulum and
      mitochondria. Additionally, Ca(2+) channel gene expression was evaluated RESULTS:
      Splenocytes showed a progressive loss of intracellular Ca(2+) maintenance from
      endoplasmic reticulum (ER) stores. Transient Ca(2+) buffering by the mitochondria
      was further compromised. These findings were confirmed by changes in
      mitochondrial integrity and in the performance of the store operated calcium
      entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca(2+) channels.
      CONCLUSIONS AND GENERAL SIGNIFICANCE: These novel data suggest that SD impairs
      Ca(2+) signaling, most likely as a result of ER stress, leading to an
      insufficient Ca(2+) supply for signaling events. Our results support the
      previously described immunosuppressive effects of sleep loss and provide
      additional information on the cellular and molecular mechanisms involved in sleep
      function.

PMID- 23000492
TI  - The abasic site lesions in the human telomeric sequence d[TA(G(3)T(2)A)(3)G(3)]:
      a thermodynamic point of view.
AB  - BACKGROUND: The abasic sites represent one of the most frequent lesions of DNA
      and most of the events able to generate such modifications involve guanine bases.
      G-rich sequences are able to form quadruplex structures that have been proved to
      be involved in several important biological processes. METHODS: In this paper, we
      report investigations, based on calorimetric, UV, CD and electrophoretic
      techniques, on 12 oligodeoxynucleotides analogues of the quadruplex forming human
      telomere sequence d[TA(G(3)T(2)A)(3)G(3)], in which each guanine has been
      replaced, one at a time, by an abasic site mimic. RESULTS: Although all data show
      that the modified sequences preserve their ability to form quadruplex structures,
      the thermodynamic parameters clearly indicate that the presence of an abasic site
      decreases their thermal stability compared to the parent unmodified sequence,
      particularly if the replacement concerns one of the guanosines involved in the
      formation of the central G-tetrad. CONCLUSIONS: The collected data indicate that
      the effects of the presence of abasic site lesions in telomeric quadruplex
      structures are site-specific. The most dramatic consequences come out when this
      lesion involves a guanosine in the centre of a G-run. GENERAL SIGNIFICANCE:
      Abasic sites, by facilitating the G-quadruplex disruption, could favour the
      formation of the telomerase primer. Furthermore they could have implications in
      the pharmacological approach targeting telomere.

PMID- 23000493
TI  - Heme binding to human alpha-1 proteinase inhibitor.
AB  - BACKGROUND: Heme is a unique prosthetic group of various hemoproteins that
      perform diverse biological functions; however, in its free form heme is
      intrinsically toxic in vivo. Due to its potential toxicity, heme binding to
      plasma proteins is an important safety issue in regard to protein therapeutics
      derived from human blood. While heme binding by hemopexin, albumin and alpha(1)
      microglobulin has been extensively studied, the role of other plasma proteins
      remains largely unknown. METHODS: We examined two acute-phase plasma proteins,
      haptoglobin (Hp) and alpha-1 proteinase inhibitor (alpha(1)-PI) for possible
      interactions with heme and bilirubin (BR), the final product of heme degradation,
      using various techniques: UV/Vis spectroscopy, fluorescence, circular dichroism
      (CD), and surface plasmon resonance (SPR). RESULTS: According to our data, Hp
      exhibits a very weak association with both heme and BR; alpha(1)-PI's affinity to
      BR is also very low. However, alpha(1)-PI's affinity to heme (K(D) 2.0*10(-8)M)
      is of the same order of magnitude as that of albumin (1.26*10(-8)M). The data for
      alpha(1)-PI binding with protoporphyrin IX (PPIX) suggest that the elimination of
      the iron atom from the porphyrin structure results in almost 350-fold lower
      affinity (K(D) 6.93*10(-6)M), thus indicating that iron is essential for the heme
      coordination with the alpha(1)-PI. CONCLUSIONS: This work demonstrates for the
      first time that human alpha(1)-PI is a heme binding protein with an affinity to
      heme comparable to that of albumin. GENERAL SIGNIFICANCE: Our data may have
      important implications for safety and efficacy of plasma protein therapeutics.

PMID- 23000494
TI  - Eight flavonoids and their potential as inhibitors of human cytomegalovirus
      replication.
AB  - The drugs currently available for treatment of severe human cytomegalovirus
      (HCMV) infections suffer from many drawbacks, particularly toxicity, and
      potential teratogenicity contraindicating their use in target populations such as
      pregnant women. The emergence of drug-resistant strains is still a problem for
      disease management, particularly in immunosuppressed populations where antivirals
      are used for extended periods of time. The flavonoid family of drugs contains
      promising candidates as they have low toxicity and inhibit different targets to
      currently available antivirals. We report here that, unlike their chalcon
      homologs, four flavonoids (baicalein, quercetin, quercetagetin and naringenin)
      inhibit various stages of HCMV replication, the most active anti-HCMV compound
      being baicalein and the less active and less selective being quercetagetin. These
      drugs could provide potential inhibitors of virus replication alone or in
      combination, without increased toxicity.

PMID- 23000495
TI  - Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine
      interferon-alpha and antiviral agents.
AB  - Foot-and-mouth disease (FMD) is an economically significant animal disease
      because of the speed of its transmission. The current FMD vaccine provides no
      protection until 7days after the vaccination, which reduces its effectiveness in
      the case of an outbreak. Therefore, to find an alternative method of applying
      antiviral agents for rapid and enhanced inhibition of the FMD virus (FMDV), we
      compared the antiviral effects of promising antiviral agents and attempted to
      apply them in combination. First, we measured and compared the 50% effective
      concentration (EC(50)) to the mean inhibition effects of FMDV, and the 50%
      cytotoxic concentration (CC(50)) to the mean cytotoxicity of antiviral agents
      such as ribavirin, guanidine-hydrochloride (guanidine-HCl), 6-azauridine, and
      recombinant adenovirus expressing three small interference RNAs (Ad-siRNA) or
      porcine interferon-alpha (Ad-porcine IFN-alpha) in swine kidney cells (IBRS-2).
      The selectivity indices of ribavirin (35.2) and 6-azauridine (34.6) were higher
      than that of guanidine-HCl (26.9). The selectivity indices of Ad-siRNA or Ad
      porcine IFN-alpha were 7*10(3) or 7*10(4) based on the adenoviral titer. Next, we
      tested the combined effects of the FMDV inhibition agents. Enhanced inhibition
      effects were observed in the IBRS-2 cells and in suckling mice from the
      combination of Ad-porcine IFN-alpha and Ad-siRNA or ribavirin. The combined
      application of these recombinant adenoviruses and ribavirin may enhance their
      inhibitory effect on FMDV and overcome FMDV resistance against antiviral agents.

PMID- 23000496
TI  - In vitro profiling of the vaginal permeation potential of anti-HIV microbicides
      and the influence of formulation excipients.
AB  - In the search for an effective anti-HIV microbicidal gel, limited drug
      penetration into the vaginal submucosa is a possible reason for failed protection
      against HIV transmission. To address this issue in early development, we here
      describe a simple in vitro strategy to predict the tissue permeation potential of
      vaginally applied drugs, based on solubility, permeability and flux assessment.
      We demonstrated this approach for four model microbicides (tenofovir, darunavir,
      saquinavir mesylate and dapivirine) and additionally examined the influence of
      formulation excipients on the permeation potential. When formulated in an aqueous
      based HEC gel, high flux values across an HEC-1A cell layer were reached by
      tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir
      and dapivirine fluxes remained low due to poor permeability and solubility,
      respectively. These low fluxes suggest limited in vivo tissue penetration,
      possibly leading to lack of efficacy. Dapivirine fluxes, however, could be
      enhanced up to 30-fold, by including formulation excipients such as polyethylene
      glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative
      formulations, i.e. emulsions or silicone elastomer gels, were less effective in
      flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing
      the proposed solubility and permeability profiling in early microbicide
      development may contribute to the successful selection of promising microbicide
      candidates and appropriate formulations.

PMID- 23000497
TI  - Chest compressions in the emergency department: rate does not have to compromise
      compression depth.

PMID- 23000498
TI  - Cardiac arrests in schools: assessing use of automated external defibrillators
      (AED) on school campuses.
AB  - BACKGROUND: Sudden cardiac arrest in schools are infrequent, but emotionally
      charged events. The purpose of our study was to: (1) describe characteristics and
      outcomes of school cardiac arrests; and (2) assess the feasibility of conducting
      school bystander interviews to describe the events surrounding cardiac arrests,
      assess AED availability and use, and identify barriers to AED use. METHODS: We
      performed a telephone survey of bystanders to cardiac arrests occurring in K-12
      schools in communities participating in the Cardiac Arrest Registry to Enhance
      Survival (CARES) database and a local cardiac arrest database. The study period
      was from 8/2005 to 8/2011 and continued in one community through 2011. Utstein
      style descriptive data and outcomes were collected. A structured telephone
      interview of a bystander or administrative personnel was conducted for each
      cardiac arrest event. We collected a descriptive event summary, including
      provision of bystander CPR, presence of an AED and information regarding AED
      deployment, training, and use and perceived barriers to AED use. Descriptive data
      are reported. RESULTS: During the study period there were 30,603 cardiac arrests
      identified at study communities, of which 47 (0.15%) events were at K-12 schools.
      Of these, 21 (45.7%) were at high schools, a minority (16, 34.0%) were children
      (<age 19), most (39, 83.0%) were witnessed arrests, a majority (36, 76.6%)
      received bystander CPR, and 27 (57.4%) were initially in ventricular fibrillation
      (VF). Most arrests (28/40, 70%) occurred during the school day (7a-5p). From this
      population, 15 (31.9%) survived to hospital discharge. A telephone interview was
      completed for 30 of 47 K-12 events. Nineteen schools had an AED on site. Most
      schools (84.2%) with AEDs reported that they had a training program, and
      personnel identified for its use. An AED was applied in 11 of 19 patients, of
      these 8 were in VF and 4 (all VF) survived to hospital discharge. Bystanders
      identified multiple reasons for non-use of the AED in the other eight patients.
      CONCLUSIONS: Cardiac arrests in schools are rare events, most patients are adults
      and receive bystander CPR. AED application by laypersons was infrequent but
      resulted in excellent (4/11) survival. AEDs were not used in a substantial
      proportion of incidents and further attention must be paid to planning for
      emergency response on school campuses. We also identified the difficulty in
      assessing school emergency care and advocate for the development of methods to
      evaluate the provision of emergency care on school campuses.

PMID- 23000499
TI  - Is discharge-on-scene policy really safe after naloxone reversal of acute long
      acting opioid toxicity?

PMID- 23000500
TI  - IL-19 and IL-20 genes polymorphisms and haplotype analysis in a vesicoureteral
      reflux population.
AB  - Vesicoureteral reflux (VUR) is a common childhood problem, causing renal wounds
      and escalating the risk of renal deficiency and hypertension. A vast literature
      exists suggesting that genetic variations play a significant role in the
      pathogenesis of VUR. The aim of the present study was to estimate whether genetic
      polymorphisms of IL-19 (GC rs2243158, AT rs2243158) and IL-20 (AG rs2981573, TG
      rs2981572) genes are involved in the development of VUR. MATERIALS AND METHODS:
      The tetra amplification mutation refractory system-polymerase chain reaction
      (Tetra-ARMS PCR) was applied for analyzing four polymorphic sites of IL-19 (GC
      rs2243158, AT rs2243158) and IL-20 (AG rs2981573, TG rs2981572) genes in 110
      healthy controls and 124 VUR children. RESULTS: A significant association was
      found between the combined genotypes of IL19GC+CC and IL20TG+GG and increased
      risk of VUR (OR = 1.90, 95% CL, 1.06-3.41; OR=1.87, 95% CL, 1.06-3.29,
      respectively). The frequency of allele G in both sites of IL-20 (IL20AG rs2981573
      and IL20TG, rs2981572) showed a statistically significant difference (p = 0.01)
      between cases and controls in comparison with the wild type. The combined
      haplotype analysis of IL-19 and IL-20 polymorphic sites revealed that HT2, HT3
      and HT5 haplotypes marginally increased the risk of VUR, but not statistically
      significantly. Gene-gene interaction data of IL-19 (GC rs2243158, AT rs2243158)
      and IL-20 (AG rs2981573, TG rs2981572) in various genotype patterns highlighted
      the fact that most of the genotype combinations increased the risk of disease
      insignificantly. CONCLUSION: This is the first evidence regarding IL-19 and IL-20
      cytokine genes polymorphism and risk of VUR, suggesting the need for further
      study with large sample size and in different populations to confirm the
      presented data.

PMID- 23000501
TI  - Monocyte CD40 expression in head and neck squamous cell carcinoma (HNSCC).
AB  - CD40, an antigen-presenting cell expressed costimulatory receptor molecule, binds
      to T cell expressed CD40-ligand (CD40-L). Using a mouse tumor model, we showed
      previously that lower CD40/CD40-L expression levels promoted tumor growth whereas
      higher CD40/CD40-L expression levels led to tumor regression indicating duality
      in CD40 functions. Whether CD40/CD40-L expressions are regulated in cancer
      patients is unknown. Herein, we show that the CD40 and CD40-L expressions on
      monocytes and T cells, respectively, decrease as the head and neck squamous cell
      carcinoma (HNSCC) patients progress from stage-I through stage-IV suggesting a
      novel CD40/CD40-L expression based staging of HNSCC tumor. The staging is
      confirmed by TNM and histo-pathological staging. The levels of soluble CD40
      (sCD40) and sCD40-L are also modulated in patients' plasma. As CD40 expressing
      monocytes increase in the post-operative patients, CD40 expression levels are
      possibly regulated by tumor load. This change is accompanied by increased IL-12
      expressing monocytes and decreased IL-10 expression levels. Thus, our findings on
      CD40/CD40-L expression in HNSCC patients bear significant implications.

PMID- 23000502
TI  - Cerebro-spinal fluid findings in mitochondrial disorders.

PMID- 23000503
TI  - An integrated wastewater treatment system using a BAS reactor with biomass
      attached to tubular supports.
AB  - This paper describes laboratory experiments aimed to develop a new wastewater
      treatment system as an alternative to a conventional domestic wastewater plant. A
      modified Biofilm Airlift Suspension reactor (BAS), with biomass attached to
      tubular supports, is proposed to address low organic loads (typical of domestic
      sewage) and low residence time (typical of compact reactors technology). Attached
      and suspended biomasses, coupled to the high dissolved oxygen (DO), allow high
      removal efficiencies (90% and 56% for COD and N-NH(4)(+) removal respectively)
      and high effluent quality to be reached. The experimental activity, divided into
      three parts, demonstrates the good efficiency of the process, and the reduction
      of the removal kinetics for the high operating pressure used in the technology.
      The occurrence of simultaneous nitrification-denitrification (SND) was also
      observed. When compared with the conventional BAS system, the present treatment
      shows comparable removal efficiencies and higher specific removal rates (80 mg
      COD/g VSS and 2.60 mg N-NH(4)(+)/g VSS). The experimental results were coupled
      with the development of a numerical model to aid in designing a full-scale
      treatment plant in Italy.

PMID- 23000504
TI  - Landscape functionality of plant communities in the Impala Platinum mining area,
      Rustenburg.
AB  - The tremendous growth of the platinum mining industry in South Africa has
      affected the natural environment adversely. The waste produced by platinum
      mineral processing is alkaline, biologically sterile and has a low water-holding
      capacity. These properties in the environment may constitute dysfunctional areas
      that will create 'leaky' and dysfunctional landscapes, limiting biological
      development. Landscape Function Analysis (LFA) is a monitoring procedure that
      assesses the degradation of landscapes, as brought about by human, animal and
      natural activities, through rapidly assessing certain soil surface indicators
      which indicate the biophysical functionality of the system. The "Trigger-Transfer
      Reserve-Pulse" (TTRP) conceptual framework forms the foundation for assessing
      landscape function when using LFA. The two main aspects of this framework are the
      loss of resources from the system and the utilisation of resources by the system.
      After a survey of landscape heterogeneity to reflect the spatial organisation of
      the landscape, soil surface indicators are assessed within different patch types
      (identifiable units that retains resources that pass through the system) and
      interpatches (units between patches where vital resources are not retained, but
      lost) to assess the capacity of patches with various physical properties in
      regulating the effectiveness of resource control in the landscape. Indices
      describing landscape organisation are computed by a spreadsheet analysis, as well
      as soil surface quality indices. When assembled in different combinations, three
      indices emerge that reflect soil productive potential, namely: the (1) surface
      stability, (2) infiltration capacity, and (3) the nutrient cycling potential of
      the landscape. In this study we compared the landscape functionality of natural
      thornveld areas, rehabilitated opencast mines and rehabilitated slopes of
      tailings dams in the area leased for mining in the Rustenburg area. Our results
      show that the rehabilitated areas had a higher total SSA functionality due to
      higher infiltration and nutrient cycling indices than the natural thornveld
      landscapes. The length of interpatches and the width of patches greatly
      influenced the landscape function of the studied areas. The natural thornveld
      areas had a marginally higher total patch area than the rehabilitated areas.
      Vegetated patches (grass-, sparse grass-, grassy forb-, and grassy shrub-patches)
      generally scored the highest functionality indices, whilst bare soil interpatches
      contributed to the landscape functionality of the various plant communities the
      least.

PMID- 23000505
TI  - A novel VCP mutation as the cause of atypical IBMPFD in a Chinese family.
AB  - INTRODUCTION: Inclusion-body myopathy (IBM) with Paget's disease of bone (PDB)
      and frontotemporal dementia (FTD), designated as IBMPFD, is a rare, autosomal
      dominant disorder (MIM 605382). IBMPFD is caused by mutations in the gene that
      encode valosin-containing protein (VCP). We investigated a Chinese family in
      which multiple members were diagnosed with PDB and suffered from weakness of the
      limbs. However, no members of this family were diagnosed with FTD. We made a
      preliminary diagnosis of PDB, but failed to identify an SQSTM1 mutation in any of
      the patients. We used whole-exome sequencing to identify the pathogenic gene
      mutation affecting the Chinese male proband. MATERIALS AND METHODS: Altogether,
      254 subjects, including one 56-year-old male proband, four affected, related
      individuals and additional nine family members from a non-consanguineous Chinese
      family, and 240 healthy donors were recruited and genomic DNA was extracted. All
      eight exons and the exon-intron boundaries of the SQSTM1 gene were amplified by
      polymerase chain reaction (PCR) and directly sequenced in five patients (II13,
      II4, II5, II8, II9). Using whole-exome sequencing, we identified a novel mutation
      in VCP as the disease-causing mutation. We confirmed the result by sequencing a
      500-bp region of the promoter and the coding region of VCP in all 254 of the
      participants using Sanger sequencing. RESULTS: No mutation in the SQSTM1 gene was
      identified in the five patients examined using direct Sanger sequencing. However,
      through whole-exome sequencing we were able to identify a novel missense mutation
      in exon 3 of the VCP gene (p.Gly97Glu) in the Chinese male proband. This mutation
      was confirmed using Sanger sequencing. The proband, four affected individuals and
      three unaffected individuals carried this mutation. We were able to correctly
      diagnose the patients with atypical IBMPFD. Structural analysis of the p.Gly97Glu
      mutation in the VCP protein showed that the affected amino-acid is located in the
      interface of the protein. This abnormality may therefore interfere with protein
      function. CONCLUSIONS: This is the first report of a family from China with
      IBMPFD. A novel VCP mutation was found as the cause of atypical IBMPFD in a
      Chinese family. Our findings confirm that VCP gene mutations can be a pathogenic
      cause of IBMPFD.

PMID- 23000506
TI  - Ten-year risk of second hip fracture. A NOREPOS study.
AB  - BACKGROUND: Second hip fracture risk is elevated after the first, however whether
      risk differs with age, by sex or over time is not well known. OBJECTIVE: To
      examine the risk of second hip fracture by sex, age and time after first hip
      fracture. DESIGN: Data on all hip fractures in subjects 50 years and older and
      treated in Norwegian hospitals during 1999-2008 were retrieved. Surgical
      procedure codes and additional diagnosis codes were used to define incident
      fractures. Survival analyses with and without adjustment for competing risk of
      death were used to estimate the risk of second hip fracture. RESULTS: Among the
      81,867 persons who sustained a first hip fracture, 6161 women and 1782 men
      suffered a second hip fracture during follow-up. The overall age-adjusted hazard
      ratio (HR) of a second hip fracture did not differ between the sexes (women
      versus men, HR=1.03; 95% confidence interval (CI): 0.98-1.09). Taking competing
      risk of death into account, the corresponding age-adjusted HR of a second hip
      fracture was 1.40 (95% CI: 1.33-1.47) in women compared to men. The greater risk
      in women was due to a higher mortality in men. Based on competing risk analyses,
      we estimate that 15% of women and 11% of men will have suffered a second hip
      fracture within 10 years after the first hip fracture. The ten-year cumulative
      incidence was above 10% in all age-groups, except in men 90 years and older.
      CONCLUSION: Fracture preventive strategies have a large potential in both women
      and men who suffer their first hip fracture due to the high risk of another hip
      fracture.

PMID- 23000507
TI  - Experimental tooth movement-induced osteoclast activation is regulated by
      sympathetic signaling.
AB  - Experimental tooth movement (ETM) changes the distribution of sensory nerve
      fibers in periodontal ligament and the bone architecture through the stimulation
      of bone remodeling. As the sympathetic nervous system is involved in bone
      remodeling, we examined whether ETM is controlled by sympathetic signaling or
      not. In male mice, elastic rubber was inserted between upper left first molar
      (M1) and second molar (M2) for 3 or 5 days. Nerve fibers immunoreactive for not
      only sensory neuromarkers, such as calcitonin gene-related peptide (CGRP), but
      also sympathetic neuromarkers, such as tyrosine hydroxylase (TH) and neuropeptide
      Y (NPY) were increased in the periodontal ligament during ETM. To elucidate the
      effect of the sympathetic signal mediated by ETM, mice were intraperitoneally
      injected with a beta-antagonist, propranolol (PRO: 20 MUg/g/day), or a beta
      agonist, isoproterenol (ISO: 5 MUg/g/day) from 7 days before ETM. PRO treatment
      suppressed the amount of tooth movement by 12.9% in 3-day ETM and by 32.2% in 5
      day ETM compared with vehicle treatment. On the other hand, ISO treatment
      increased it. Furthermore, ETM remarkably increased the osteoclast number on the
      bone surface (alveolar socket) (Oc.N/BS) in all drug treatments. PRO treatment
      suppressed Oc.N/BS by 39.4% in 3-day ETM, while ISO treatment increased it by
      32.1% in 3-day ETM compared with vehicle treatment. Chemical sympathectomy using
      6-hydroxydopamine (6-OHDA: 250 MUg/g) showed results similar to those for PRO
      treatment in terms of both the amount of tooth movement and osteoclast
      parameters. Our data showed that blockade of sympathetic signaling inhibited the
      tooth movement and osteoclast increase induced by ETM, and stimulation of
      sympathetic signaling accelerated these responses. These data suggest that the
      mechano-adaptive response induced by ETM is controlled by sympathetic signaling
      through osteoclast activation.

PMID- 23000508
TI  - Labeling studies on cortical bone formation in the antlers of red deer (Cervus
      elaphus).
AB  - The formation and mineralization process of antlers, which constitute the fastest
      growing bones in vertebrates, is still not fully understood. We used
      oxytetracycline injections to label different stages of bone formation in antlers
      of 14 red deer between days 28 and 156 of antler growth. Results show that
      initially a trabecular scaffold of woven bone is formed which largely replaces a
      pre-existing scaffold of mineralized cartilage. Lamellar bone is then deposited
      and from about day 70 onwards, primary osteons fill in the longitudinal tubes
      lined by the scaffold in a proximal to distal sequence. Mineral apposition rate
      (MAR) in early stages of primary osteon formation is very high (average 2.15
      MUm/d). Lower MARs were recorded for later stages of primary osteon formation
      (1.56 MUm/d) and for the smaller secondary osteons (0.89 MUm/d). Results suggest
      a peak in mineral demand around day 100 when the extent of mineralizing surfaces
      is maximal. A few secondary osteons were formed in a process of antler modeling
      rather than remodeling, as it occurred simultaneously with formation of primary
      osteons. The degree of cortical porosity reflects a reduction in MAR during later
      stages of osteonal growth, whereas cortical thickness is determined earlier.
      Injections given when the antlers were largely or completely clean from velvet
      produced no labels in antler bone, strongly suggesting that antlers are dead
      after velvet shedding. The rapidity of antler mineralization and the short
      lifespan of antlers make them an extraordinary model to assess the effects of
      chemicals impairing or promoting bone mineralization.

PMID- 23000509
TI  - TiNOx coatings on roughened titanium and CoCr alloy accelerate early
      osseointegration of dental implants in minipigs.
AB  - INTRODUCTION: Titanium nitride oxide (TiNOx) coatings are known for their
      biocompatibility, hardness and high resistance to corrosion and wear. Further,
      they can be applied by plasma vapor deposition onto a wide variety of metallic,
      mineral, or organic substrates. In cell cultures, TiNOx coatings applied onto SLA
      (sandblasted, large grit, acid etched)-roughened titanium surfaces increased
      human primary osteoblast proliferation by 1.5 times in the first 2 weeks after
      seeding, while maintaining a high degree of cell differentiation. Therefore, the
      objectives of the present study were (i) to determine whether these findings
      would translate into the enhanced osseointegration of TiNOx-coated implants in
      vivo and (ii) to compare the osseointegration of Ti-SLA (titanium-SLA) and CoCr
      SLA (cobalt-chromium-SLA) implants coated with TiNOx. METHODS: Forty-eight
      cylinders made of Ti-SLA, Ti-SLA-TiNOx (TiNOx-coated Ti-SLA) and CoCr-SLA-TiNOx
      (TiNOx-coated CoCr-SLA) were implanted into the lower jawbone of 8 minipigs. The
      bone-to-implant contact was determined after 1 week, 2 weeks, 1 month and 3
      months. RESULTS: Osseointegration proceeded normally on all 3 surfaces, with
      equal activity after the first week of healing. After 2 weeks, bone-to-implant
      contact was 1.8 times higher on TiNOx coatings, either deposited on Ti or on
      CoCr. These differences fell off after 1 and 3 months of healing. CONCLUSIONS:
      When compared to standard SLA titanium, TiNOx coatings enhance implant
      osseointegration during the first month of healing. Furthermore, this stimulating
      effect is independent of the substrate, leading to similar results whether the
      coating is applied onto SLA-Ti or onto SLA-CoCr.

PMID- 23000510
TI  - The role of TRB3 in mast cells sensitized with monomeric IgE.
AB  - Mast cells play a key role in immunoglobulin E (IgE)-associated allergic
      disorders; however, the cellular effects of sensitization remain poorly
      understood. Using gene microarrays and the multiplexing ELISA method, we examined
      the effects of sensitization on RBL-CCR1 cell transcription and
      chemokine/cytokine secretion. Sensitization most prominently increased
      transcription of Trb3, the gene for tribbles homolog 3 (TRB3), and also increased
      the release of most of the cytokines and chemokines tested. Knockdown of TRB3 via
      RNAi significantly induced the production of tumor necrosis factor-alpha (TNF
      alpha), interleukin-4 (IL-4), interleukin-6 (IL-6), and the chemokine mast cell
      protease-1 (MCP-1). TRB3 deficiency also induced IkappaBalpha phosphorylation.
      TRB3 may therefore serve as a negative regulator of pro-inflammatory cytokines
      and chemokines, controlling the extent of the inflammatory response.

PMID- 23000511
TI  - A meta-analysis of the efficacy of acupuncture in treating dysphagia in patients
      with a stroke.
AB  - BACKGROUND: Dysphagia, or deglutition difficulty, is a common manifestation in
      patients with a stroke and its management is an important aspect of
      rehabilitation. Acupuncture, a complementary and alternative therapy, is the
      subject of growing public interest for treatment of stroke. OBJECTIVE: A meta
      analysis was performed to study the effect of acupuncture for treatment of
      dysphagia in patients affected by a stroke. METHODS: Randomised controlled trials
      (RCTs) comparing acupuncture treatment with non-acupuncture treatment of
      dysphagia in patients with a stroke were identified from the databases of PubMed,
      Embase, Cochrane Library and CBM disc (China Biological Medicine Database).
      Eligible investigations were included and data on the effectiveness of
      acupuncture were extracted and synthesised by meta-analysis using RevMan 5.1.4.
      Results were expressed as OR for dichotomous data; 95% CIs were also calculated.
      RESULTS: Seventy-two RCTs (3208 patients in the treatment group and 2926 patients
      in the control group) were identified. Details of randomisation and blinding were
      not reported and information on withdrawals and dropouts was missing in most of
      included reports. Meta-analysis showed that the effectiveness of treatment in the
      group receiving acupuncture was higher than that in the non-acupuncture group
      (OR=5.17, 95% CI 4.18 to 6.38; p<0.00001). However, the study quality was
      generally low and of insufficient quality to make recommendations about using
      acupuncture in the rehabilitation of patients with dysphagia due to stroke.
      CONCLUSIONS: Acupuncture might be beneficial in the rehabilitation of patients
      with dysphagia caused by stroke, and the evidence justifies future high-quality
      studies.

PMID- 23000512
TI  - Some aspects of mutation research after a low-dose radiation exposure.

PMID- 23000513
TI  - Epileptic seizures in Japanese patients with multiple sclerosis and neuromyelitis
      optica.
AB  - PURPOSE: To examine the incidence and clinical features of epileptic seizures in
      Japanese patients with multiple sclerosis (MS) and neuromyelitis optica (NMO).
      METHODS: We reviewed medical records of all patients who visited the Neurology
      Clinic in Utano National Hospital between January and December, 2009, and
      enrolled 63 MS patients who fulfilled the McDonald criteria (2005) (mean age,
      41.1 years) and 31 NMO patients who fulfilled the Wingerchuk criteria (2006)
      (mean age, 44.6 years). Patients with a history of epileptic seizures were
      selected and their clinical features were obtained. RESULTS: Four MS patients
      (6.3%; 2 men and 2 women; mean age, 32.5 years) and 4 NMO patients (12.9%; 4
      women; mean age, 36.0 years) had epileptic seizures. Disease onset age of MS
      patients with seizures was significantly younger than those without seizures by
      13.1 years, and Expanded Disability Status Scale of NMO patient with seizures was
      significantly higher than those without seizures by 2.2. All 8 patients showed
      brain lesions on magnetic resonance imaging and 2 MS patients had tumefactive
      demyelinating lesions. Electroencephalography showed interictal epileptiform
      discharges in 5 patients. Seizure types of 6 patients were recognized as partial
      seizures based on clinical semiology. All patients responded to antiepileptic
      therapy well. In both MS and NMO, there were both seizures with and without
      concurrent relapse. CONCLUSIONS: Similar to MS, NMO patients possibly have higher
      risk to develop epileptic seizures than general population.

PMID- 23000515
TI  - Potent antitumoral effects of targeted promoter-driven oncolytic adenovirus armed
      with Dm-dNK for breast cancer in vitro and in vivo.
AB  - Currently, no curative treatments are available for late-stage metastatic or
      recurrent breast cancer, because the cancer tolerates both chemotherapy and
      endocrine therapy. In this study, we investigated the feasibility of a dual
      regulated oncolytic adenoviral vector with a novel suicide gene to treat breast
      cancer. Following targeted gene virotherapy of conditionally replicating
      adenoviruses (CRAds), the novel suicide gene of multisubstrate
      deoxyribonucleoside kinase of Drosophila melanogaster (Dm-DNK) was inserted into
      the double-regulated oncolytic adenovirus SG500 to ensure more safety and
      enhanced antitumor activity against breast cancer both in vitro and in vivo.
      Selective replication, cell-killing efficacy, and cytotoxicity, combined with
      chemotherapeutics were investigated in several breast cell lines (MDA-MB-231 and
      MCF-7), normal cells (WI-38 and MRC-5), and human (MDA-MB-231) tumor models in
      vivo. The double-regulated SG500-dNK had high cell-killing activity in breast
      cancer. Replication was similar to wild-type in breast cells and was attenuated
      in normal cells. SG500-dNK combined with the chemotherapeutics (E)-5-(2
      bromovinyl)-2'-deoxyuridine (Bvdu) and 2',2'-difluoro-deoxycytidine (dFdC)
      resulted in synergistically enhanced cell killing and greatly improved antitumor
      efficacy in vitro or in breast xenografts in vivo. These data suggest that the
      novel oncolytic variant SG500-dNK is a promising candidate for targeting breast
      tumors specifically when combined with chemotherapeutics.

PMID- 23000514
TI  - Porous silicon nanocarriers for dual targeting tumor associated endothelial cells
      and macrophages in stroma of orthotopic human pancreatic cancers.
AB  - Pancreatic cancer is a highly fatal disease characterized by a dominant stroma
      formation. Exploring new biological targets, specifically those overexpressed in
      stroma cells, holds significant potential for the design of specific nanocarriers
      to attain homing of therapeutic and imaging agents to the tumor. In clinical
      specimens of pancreatic cancer, we found increased expression of CD59 in tumor
      associated endothelial cells as well as infiltrating cells in the stroma as
      compared to uninvolved pancreas. We explored this dual targeting effect using
      orthotopic human pancreatic cancer in nude mice. By immunofluorescence analysis,
      we confirmed the increased expression of Ly6C, mouse homolog of CD59, in tumor
      associated endothelial cells as well as in macrophages within the stroma. We
      decorated the surface of porous silicon nanocarriers with Ly6C antibody. Targeted
      nanocarriers injected intravenously accumulated to tumor associated endothelial
      cells within 15min. At 4h after administration, 9.8+/-2.3% of injected dose/g
      tumor of the Ly6C targeting nanocarriers accumulated in the pancreatic tumors as
      opposed to 0.5+/-1.8% with non-targeted nanocarriers. These results suggest that
      Ly6C (or CD59) can serve as a novel dual target to deliver therapeutic agents to
      the stroma of pancreatic tumors.

PMID- 23000516
TI  - GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma
      cells to lysosomal membrane permeabilization and cell death.
AB  - Since phosphatidylinositol-3-kinase (PI3K) inhibitors are primarily cytostatic
      against glioblastoma, we searched for new drug combinations. Here, we discover
      that the PI3K inhibitor GDC-0941 acts in concert with the natural compound B10, a
      glycosylated derivative of betulinic acid, to induce cell death in glioblastoma
      cells. Importantly, parallel experiments in primary glioblastoma cultures
      similarly show that GDC-0941 and B10 cooperate to trigger cell death,
      underscoring the clinical relevance of this finding. Molecular studies revealed
      that treatment with GDC-0941 stimulates the expression and nuclear translocation
      of Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis,
      the lysosomal membrane marker LAMP-1 and the mature form of cathepsin B. Also,
      GDC-0941 triggers a time-dependent increase of the lysosomal compartment in a
      TFEB-dependent manner, since knockdown of TFEB significantly reduces this GDC
      0941-stimulated lysosomal enhancement. Importantly, GDC-0941 cooperates with B10
      to trigger lysosomal membrane permeabilization, leading to increased activation
      of Bax, loss of mitochondrial membrane potential (MMP), caspase-3 activation and
      cell death. Addition of the cathepsin B inhibitor CA-074me reduces Bax
      activation, loss of MMP, caspase-3 activation and cell death upon treatment with
      GDC-0941/B10. By comparison, knockdown of caspase-3 or the broad-range caspase
      inhibitor zVAD.fmk inhibits GDC-0941/B10-induced DNA fragmentation, but does not
      prevent cell death, thus pointing to both caspase-dependent and -independent
      pathways. By identifying the combination of GDC-0941 and B10 as a new, potent
      strategy to trigger cell death in glioblastoma cells, our findings have important
      implications for the development of novel treatment approaches for glioblastoma.

PMID- 23000517
TI  - Gamma-tocotrienol, a radiation prophylaxis agent, induces high levels of
      granulocyte colony-stimulating factor.
AB  - Gamma-tocotrienol (GT3), a promising radioprotectant, is shown to protect CD2F1
      mice from radiation-induced neutropenia and thrombocytopenia when given 24h prior
      to total-body irradiation. GT3 also is shown to increase white blood cells (WBC)
      and absolute neutrophil counts (ANC) transiently in peripheral blood. We
      hypothesized that increases in WBC and ANC may involve stimulation of
      hematopoiesis possibly by cytokines and growth factors. To evaluate the effects
      of GT3 on hematopoietic system, we measured various cytokines, chemokines and
      growth factors by cytokine array and Bio-Plex assays. Both showed strong
      induction of various cytokines and chemokines. GT3 treatment resulted in
      significant increases in G-CSF, IL-1alpha, IL-1beta, IL-6, IL-12p70, IL-17, MIP
      1alpha, and KC levels. G-CSF levels increased markedly within 12-24h after
      administration (5441 pg/ml in GT3-treated groups compared to 17 pg/ml in vehicle
      control). Most of these cytokine levels were elevated in the presence or absence
      of radiation. Time-course analysis of G-CSF and IL-6 induction showed that both
      cytokines were induced transiently after GT3 administration, and returned to
      normal levels by 48 h post-administration. For G-CSF, the peak was observed
      between 12 and 24h post-administration of GT3; however, the highest levels of IL
      6 were obtained between 6 and 12h. These results demonstrate that GT3 induced
      high levels of G-CSF and other inflammatory cytokines and chemokines within 24h
      after administration. Survival studies reported showed that the most efficacious
      time for administering GT3 was 24h prior to irradiation, possibly because it
      induced key hematopoietic cytokines in that time window. These results also
      suggest a possible role of GT3-induced G-CSF stimulation in protecting mice from
      radiation-induced neutropenia and thrombocytopenia.

PMID- 23000518
TI  - RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor
      necrosis factor alpha-induced L929 cell necroptosis and autophagy.
AB  - Tumor necrosis factor alpha (TNFalpha) induces necroptosis and autophagy;
      however, the detailed molecular mechanism is not fully understood. In this study,
      we found that TNFalpha administration caused mitochondrial dysfunction and
      reactive oxygen species (ROS) production, which led to necroptosis and autophagy
      in murine fibrosarcoma L929 cells. Notably, the RIP1 (serine-threonine kinase
      receptor-interacting protein 1, a main adaptor protein of necroptosis) specific
      inhibitor necrostatin-1 (Nec-1) recovered mitochondrial dysfunction and ROS
      production due to TNFalpha administration. Moreover, pan-caspase inhibitor z-VAD
      fmk (zVAD) increased RIP1 expression and exacerbated TNFalpha-induced
      mitochondrial dysfunction and ROS production, indicating that RIP1 led to
      mitochondrial dysfunction and ROS production. In addition, cytochrome c release
      from mitochondria was accompanied with TNFalpha administration, and Nec-1 blocked
      the release of cytochrome c upon TNFalpha administration, while zVAD enhanced the
      release. These further suggested that RIP1 induced mitochondrial dysfunction
      accompanied with cytochrome c release. Furthermore, autophagy inhibitor 3
      methyladenine (3MA) did not affect RIP1 expression as well as mitochondrial
      dysfunction and ROS production. Together with our previous publication that
      autophagy was a downstream consequence of necroptosis, we concluded that TNFalpha
      induced mitochondrial dysfunction accompanied with ROS production and cytochrome
      c release via RIP1, leading to necroptosis and resulting autophagic cell death.

PMID- 23000519
TI  - Protosappanin A inhibits oxidative and nitrative stress via interfering the
      interaction of transmembrane protein CD14 with Toll-like receptor-4 in
      lipopolysaccharide-induced BV-2 microglia.
AB  - Oxidative and nitrative stresses have been established to play a pivotal role in
      neuroinflammation. During inflammation-mediated neurodegenerative diseases,
      including Alzheimer's disease and Parkinson's disease, reactive oxygen species
      (ROS) and nitric oxide (NO) are produced by activated microglia, further inducing
      increased neuronal injury in the brain. Protosappanin A (PTA) is a bioactive
      compound isolated from a traditional Chinese medicine, Caesalpinia sappan L.
      (Lignum Sappan), showing immunosuppressive effects. However, the molecular
      mechanisms responsible for the anti-oxidative and nitrative activity of PTA have
      not been elucidated, particularly in central nervous system. In this study, we
      found that PTA significantly inhibited ROS and NO production by suppression of
      NADPH oxidase and inducible nitric oxide synthase (iNOS) activity on
      lipopolysaccharide (LPS)-stimulated BV-2 microglia. Moreover, PTA modulated
      IKK/IkappaB/NF-kappaB inflammation signal pathway to inhibit the activity and
      expressions of NADPH oxidase and iNOS. A further study indicated that PTA didn't
      inhibit LPS interaction with transmembrane protein CD14, which is a receptor for
      LPS binding. However, PTA interfered with the interaction of CD14 with Toll-like
      receptor (TLR4), an early cell event of IKK/IkappaB/NF-kappaB inflammation signal
      activation, resulting in a block on LPS translocation from CD14 to TLR4.
      Therefore, CD14/TLR4 interaction may be a potential drug target in
      neuroinflammation-related oxidative and nitrative stress. Taken together, these
      results suggest that PTA has anti-oxidative/nitrative activities on brain immune
      and neuroinflammation through regulation of CD14/TLR4-dependent IKK/IkappaB/NF
      kappaB inflammation signal pathway.

PMID- 23000521
TI  - Decellularized bovine intervertebral disc as a natural scaffold for xenogenic
      cell studies.
AB  - Low back pain that is associated with disc degeneration contributes to a huge
      economic burden in the worldwide healthcare system. Traditional methods, such as
      spinal fusion, have been adopted to relieve mechanical back pain, but this is
      compromised by decreased spinal motion. Tissue engineering has attracted much
      attention, and aims to correct the changes fundamentally occurring in the discs
      by a combination of cell biology, molecular biology and engineering. Synthetic
      materials including poly(l-lactic acid) or poly(glycolic acid) and biomolecules
      like hyaluronic acid or collagen have been adopted in the development of disc
      scaffolds for studying therapeutic approaches. Nevertheless, the complex
      biological and mechanical environment of the intervertebral disc (IVD) makes the
      synthesis of an artificial IVD with biomaterials a difficult task. Thus the aim
      of this study was to develop a natural disc scaffold for culturing disc cells for
      future development of biological disc constructs. We adopted a combination of
      currently used decellularization techniques to decellularize bovine IVD to create
      a complete endplate-to-endplate IVD scaffold. By altering the chemical and
      physical decellularization parameters, we reported the removal of up to 70% of
      the endogenous cells, and were able to preserve the glycosaminoglycan content,
      collagen fibril architecture and mechanical properties of the discs. The
      reintroduction of nucleus pulposus cells into the scaffold indicated a high
      survival rate over 7days, with cell penetration. We have shown here that
      conventional methods used for decellularizing thin tissues can also be applied to
      large organs, such as IVD. Our findings suggest the potential of using
      decellularized IVD as a scaffold for IVD bioengineering and culturing of cells in
      the context of the IVD niche.

PMID- 23000520
TI  - Combined TCRG and TCRA TREC analysis reveals increased peripheral T-lymphocyte
      but constant intra-thymic proliferative history upon ageing.
AB  - T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and
      peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T
      lymphocyte proliferation. However, quantitative insight into thymocyte and T
      lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR
      excision circle (TREC) assay, the Vgamma-Jgamma TREC assay, which we used
      together with an adjusted deltaREC-psiJalpha TREC assay to quantify the
      proliferative history of human thymocyte and T-lymphocyte subpopulations from
      children and adults. This revealed that thymocytes undergo ~6-8 intra-thymic cell
      divisions from the double negative (DN) 3 developmental stage onwards, which
      appeared independent of age. Thus thymocyte proliferation after the DN3
      developmental stages is stable and therefore not contributing to the reduced
      thymic output upon ageing. Cord blood naive T lymphocytes had already undergone
      ~2-3 post-thymic cell divisions, which increased to ~6-7 cell divisions in naive
      T lymphocytes of middle-aged adults, indicating the importance of homeostatic
      naive T-lymphocyte proliferation from a young age onwards in the maintenance of
      peripheral T-lymphocyte numbers. In conclusion, our data provide quantitative
      insight into the proliferative history of thymocyte and T-lymphocyte
      subpopulations and alterations herein upon ageing. This novel TREC assay approach
      could prove valuable in immune status monitoring in a variety of conditions.

PMID- 23000522
TI  - A new treatment alternative for sensitive teeth: a desensitizing oral rinse.
AB  - OBJECTIVE: Tooth sensitivity is a common, painful dental condition. Consumer
      dental products, mostly dentifrices, play an important role in sensitivity
      treatment. The objective of this review is to describe a new mouthwash-based
      desensitizing technology. DATA: Background literature concerning desensitizing
      products is reviewed. Potassium salts are the most commonly used active
      ingredients in desensitizing dentifrices. Clinical studies show that while
      potassium salt dentifrices are generally effective; most formulations require
      several weeks to exert their desensitizing effect. Recently, a new desensitizing
      dentifrice containing the amino acid arginine was introduced. This dentifrice
      acts to occlude the dentinal tubules, and has been shown to be highly effective
      in multiple clinical studies. This arginine-containing dentifrice has also been
      shown to provide instant relief of sensitivity pain when applied directly to the
      sensitive tooth surface. In contrast to dentifrices, there are few desensitizing
      mouthwashes available. Building on the success of the arginine-based dentifrice,
      an arginine-based mouthwash formula was developed and tested. SOURCES: Published
      studies in peer-reviewed publications. STUDY SELECTION: Controlled and blinded
      clinical studies to provide evidence of efficacy. In vitro studies are included
      to indicate the mechanism of action. This review includes studies testing the new
      arginine-based desensitizing mouthwash. CONCLUSION: Clinical findings indicate
      that this new desensitizing mouthwash, based on the Pro-ArginTM mouthwash
      technology effectively reduces sensitivity symptoms and can be used alone or as a
      adjunct to the use of the arginine-containing dentifrice in the home treatment of
      tooth sensitivity.

PMID- 23000523
TI  - Hydrolytic degradation of the resin-dentine interface induced by the simulated
      pulpal pressure, direct and indirect water ageing.
AB  - OBJECTIVES: The aim of this study was to compare the hydrolytic effects induced
      by simulated pulpal pressure, direct or indirect water exposure within the resin
      dentine interfaces created with three "simplified" resin bonding systems (RBSs).
      METHODS: A two-step/self-etching (CSE: Clearfil SE Bond), one-step/self-etching
      (S3: Clearfil S3) and etch-and-rinse/self-priming (SB: Single-bond 2) adhesives
      were applied onto dentine and submitted to three different prolonged (6 or 12
      months) ageing strategies: (i) Simulated Pulpal Pressure (SPP); (ii) Indirect
      Water Exposure (IWE: intact bonded-teeth); (iii) Direct Water Exposure (DWE:
      resin-dentine sticks). Control and aged specimens were submitted to microtensile
      bond strength (MUTBS) and nanoleakage evaluation. Water sorption (WS) survey was
      also performed on resin disks. Results were analysed with two-way ANOVA and
      Tukey's test (p < 0.05). RESULTS: The MUTBS of CS3 and SB dropped significantly
      (p < 0.05) after 6 months of SPP and DWE. CSE showed a significant MUTBS
      reduction only after 12 months of DWE (p = 0.038). IWE promoted no statistical
      change in MUTBS (p > 0.05) and no evident change in nanoleakage. Conversely, SPP
      induced a clear formation of "water-trees" in CS3 and SB. WS outcomes were CS3 >
      SB = CSE. CONCLUSION: The hydrolytic degradation of resin-dentine interfaces
      depend upon the type of the in vitro ageing strategy employed in the experimental
      design. Direct water exposure remains the quickest method to age the resin
      dentine bonds. However, the use of SPP may better simulate the in vivo scenario.
      However, the application of a separate hydrophobic solvent-free adhesive layer
      may reduce the hydrolytic degradation and increase the longevity of resin-dentine
      interfaces created with simplified adhesives.

PMID- 23000524
TI  - Effect of tricalcium silicate (Ca(3)SiO(5)) bioactive material on reducing enamel
      demineralization: an in vitro pH-cycling study.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of Ca(3)SiO(5) on
      reducing enamel demineralization under pH-cycling conditions. METHODS: Forty
      bovine enamel samples were treated under four conditions: group 1, double
      distilled water (negative control); group 2, 1000 ppm F (as NaF, positive
      control); group 3, Ca(3)SiO(5) slurry; and group 4, Ca(3)SiO(5)-F slurry
      (Ca(3)SiO(5) with 1000 ppm F aq.). All the specimens were treated with treatment
      materials 4 times each day. Samples in groups 1 and 2 were soaked in test
      solutions for 2 min and samples in groups 3 and 4 were painted in treatment
      slurry for 2 min. At times between treatments, they were immersed in citric acid
      solution 3 times a day and 15 s each time. All the procedures were repeated for 7
      days. Knoop microhardness, scanning electron microscopy (SEM), X-ray diffraction
      (XRD) and atom force microscopy (AFM) were used to examine samples. RESULTS:
      After treatment for 7 days, enamels in all the groups were significantly
      softened. The extents of microhardness reduction were 52.3%, 28.5%, 28.5% and
      20.2% for groups 1, 2, 3 and 4, respectively. Samples in the negative control
      group showed a typical acid etched pattern while enamels in other groups were
      relatively compact. There was no significant difference between samples treated
      with Ca(3)SiO(5) and F. The combination of Ca(3)SiO(5) with F showed the best
      effect on reducing enamel demineralization. CONCLUSIONS: Ca(3)SiO(5) is an
      effective material against enamel demineralization alone but in combination with
      F a better anti-demineralization effect may be obtained.

PMID- 23000525
TI  - A randomised trial on simplified and conventional methods for complete denture
      fabrication: masticatory performance and ability.
AB  - OBJECTIVES: To compare a simplified method to a conventional protocol for
      complete denture fabrication regarding masticatory performance and ability.
      METHODS: A sample was formed by edentulous patients requesting treatment with
      maxillary and mandibular complete dentures. Participants were randomly divided
      into two groups: Group S, which received dentures fabricated by a simplified
      method, and Group C (n=21 each), which received conventionally fabricated
      dentures. After three months following insertion, masticatory performance was
      evaluated by a colorimetric assay based on chewing two capsules as test food
      during twenty and forty cycles. Masticatory ability was assessed by a
      questionnaire with binary answers and a single question answered by means of a 0
      10 scale. A third group (DN) formed by seventeen dentate volunteers served as an
      external comparator. Groups were compared by statistical tests suitable for data
      distribution (alpha=0.05). RESULTS: Thirty-nine participants were assessed for
      three months (twenty from Group C and nineteen from Group S). Groups C and S
      presented similar masticatory performance which corresponded to approximately 30%
      of Group DN. Results for masticatory ability showed similarity between S and C,
      regardless of the assessment method, although an isolate questionnaire item
      showed more favourable results for the first group. CONCLUSIONS: The simplified
      method for complete denture fabrication is able to restore masticatory function
      to a level comparable to a conventional protocol, both physiologically and
      according to patient's perceptions. CLINICAL SIGNIFICANCE: Although masticatory
      function is impaired by the loss of natural teeth and dentures can restore only a
      fraction of such function, patients can benefit from a simplified protocol for
      complete denture fabrication to the same extent they would by conventional
      techniques.

PMID- 23000526
TI  - Using Little's Irregularity Index in orthodontics: outdated and inaccurate?
AB  - OBJECTIVES: Little's Irregularity Index (LII) was devised to objectively score
      mandibular incisor alignment for epidemiological studies but has been extended to
      assess the relative performance of orthodontic brackets, retainer or treatment
      modalities. Our aim was to examine the repeatability and precision of LII
      measurements of four independent examiners on the maxillary arch of orthodontic
      patients. The hypothesis was that the reproducibility of individual contact point
      displacement measurements, used to calculate the LII score, are inappropriate.
      METHODS: The displacement of the anterior contact points, of the six upper labial
      segment teeth of the maxillary arch on each of ten casts, were randomly assessed
      by four examiners at three time-points using LII. RESULTS: Significant
      correlations were evident between the six examiner-pairs (r > 0.413; p < 0.001)
      for contact point displacements of >0.5 mm. The coefficients of variation showed
      that 516 of the 600 individual contact point displacement measurements differed
      by >20% of the mean. Analyses of variance revealed significant differences (p <
      0.047) between examiners for 46% of the contact point displacement measurements.
      CONCLUSION: The reproducibility of individual contact point displacement
      measurements, used to calculate the LII score, is poor such that using LII to
      assess the performance of orthodontic brackets, retainers or treatment modalities
      must emphatically be discouraged. CLINICAL SIGNIFICANCE: The use of LII by the
      orthodontic community to predictably determine the outcome of orthodontic
      treatment modalities in clinical practice cannot be advocated due to the limited
      accuracy and precision of the technique.

PMID- 23000527
TI  - Report from the Falk Workshop on Microscopic Colitis: creating awareness for an
      underappreciated disease.

PMID- 23000528
TI  - Teaching well matters: tips for becoming a successful medical teacher.

PMID- 23000529
TI  - A higher inherent trait for fearfulness is associated with increased anxiety-like
      behaviours and diazepam sensitivity in Japanese quail.
AB  - This study tested whether lines of Japanese quails divergently selected for a
      fear response, the tonic immobility, might constitute a reliable bird model for
      studying anxiety. Previous studies demonstrated that the selection modifies the
      general underlying emotionality of the birds rather than exerting its effect only
      on tonic immobility. The behavioural effects of intraperitoneal injections of
      diazepam, an anxiolytic drug, were assessed in two lines of quail selected either
      for their short (STI) or long (LTI) duration of tonic immobility. Effects of
      diazepam were examined in two tests used for measuring emotionality in birds, the
      open field and the tonic immobility tests. After being placed in the centre of
      the open field, birds with a high emotionality (LTI quails) stayed longer in the
      centre of the apparatus than STI quail. Diazepam had anxiolytic effect in LTI
      birds as it increased the time spent in the outer area. This effect of diazepam
      appears to be selective because the drug has no effect on other behaviours such
      as distress calls or escape attempts. The drug has also no effect on the tonic
      immobility response in any of the two lines. These findings reveal an
      "anxiogenic" trait of LTI birds in the open field test that can be modulated by
      the administration of an anxiolytic drug. Therefore quails selected for LTI and
      STI represent a valuable model to study the mechanisms underlying anxiety in
      birds.

PMID- 23000530
TI  - Therapeutic potential of histaminergic compounds in the treatment of addiction
      and drug-related cognitive disorders.
AB  - Addiction is a behavioral disorder characterized by the compulsive seeking and
      taking of drugs despite serious negative consequences. In particular, the chronic
      use of drugs impairs memory and cognitive functions, which aggravates the loss of
      control over drug use and complicates treatment outcome. Therefore, cognitive
      enhancers targeting acetylcholine have been proposed to treat addiction.
      Interestingly, histamine H(3) receptor (H(3)R) antagonists/inverse agonists
      stimulate acetylcholine transmission in different brain areas, facilitate memory
      in animal models and can reverse learning deficits induced by drugs such as
      scopolamine, dizocilpine and alcohol. Moreover, several studies found that
      compounds capable of activating the histaminergic system generally decrease the
      reinforcing effects of drugs, namely alcohol and opioids, in preclinical models
      of addiction. Finally, several H(3)R antagonists/inverse agonists increase
      histamine in the brain and have proven to be safe in humans. However, no studies
      have yet investigated the therapeutic potential of cognitive enhancing H(3)R
      antagonists/inverse agonists in the treatment of addiction in humans. The present
      review first describes the impact of addictive drugs on learning processes and
      cognitive functions that play an important role for addicts to remain abstinent.
      Second, our work briefly summarizes the relevant literature describing the
      function of histamine in learning, memory and drug addiction. Finally, the
      potential therapeutic use of histaminergic agents in the treatment of addiction
      is discussed. Our review suggests that histaminergic compounds like H(3)R
      antagonists/inverse agonists may improve the treatment outcome of addiction by
      reversing drug-induced cognitive deficits and/or diminishing the reinforcing
      properties of addictive drugs, especially opioids and alcohol.

PMID- 23000531
TI  - Caffeine prevents cognitive impairment induced by chronic psychosocial stress
      and/or high fat-high carbohydrate diet.
AB  - Caffeine alleviates cognitive impairment associated with a variety of health
      conditions. In this study, we examined the effect of caffeine treatment on
      chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced
      impairment of learning and memory in rats. Chronic psychosocial stress, WD and
      caffeine (0.3 g/L in drinking water) were simultaneously administered for 3
      months to adult male Wistar rats. At the conclusion of the 3 months, and while
      the previous treatments continued, rats were tested in the radial arm water maze
      (RAWM) for learning, short-term and long-term memory. This procedure was applied
      on a daily basis to all animals for 5 consecutive days or until the animal
      reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC
      is the number of days that the animal takes to make zero error in two consecutive
      days. Chronic stress and/or WD groups caused impaired learning, which was
      prevented by chronic caffeine administration. In the memory tests, chronic
      caffeine administration also prevented memory impairment during chronic stress
      conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and
      stress/WD groups indicated that caffeine normalizes memory impairment in these
      groups. These results showed that chronic caffeine administration prevented
      stress and/or WD-induced impairment of spatial learning and memory.

PMID- 23000532
TI  - Lifespan development: the effects of typical aging on theory of mind.
AB  - Whether typical aging is associated with impairments in social understanding is a
      topic of critical importance in characterizing the changes that occur in older
      adulthood. Theory of mind (ToM) refers to the ability to represent other's mental
      states, and has been tested in a variety of different paradigms in older adults.
      The overarching research question has been whether ToM abilities may rely on
      other cognitive abilities, such as processing speed or executive functioning, and
      as such declines in ToM may reflect a decline in general meta-representational
      abilities. Alternatively, ToM abilities may be relatively spared, suggesting the
      acquisition of a sort of social wisdom with advancing age. The preponderance of
      the evidence is in line with the first possibility: namely, ToM, as measured by
      paradigms involving faces, cartoons, stories, and videos is typically impaired in
      social aging, and these impairments are at least partly mediated by impairments
      in executive functions and fluid intelligence (but not typically by crystallized
      intelligence). Neuroimaging investigations suggest that older adults who perform
      as well as younger adults may activate compensatory mechanisms, but are impaired
      in the brain mechanisms most closely associated with ToM ability when their task
      performance is impaired. Recent methodological advances allowing continuous
      rather than categorical assessment of ToM show that ToM may be observed to
      function independently from general cognition in aging, but further investigation
      is needed to confirm this point. Implications of these findings for the
      longstanding discussion regarding Theory of Mind's endangered status as a special
      cognitive module are discussed.

PMID- 23000533
TI  - c-Fos activation and intermale aggression in rats selected for behavior toward
      humans.
AB  - Tame and aggressive rat lines were created during the long-term selection of
      Norway rats for elimination and enhancement of aggressiveness toward humans,
      respectively. Our previous experiments have demonstrated that selection for the
      elimination of defensive aggression toward humans is associated with attenuated
      intraspecific intermale aggression. However, the neuronal mechanisms underlying
      low and high intermale aggression in the tame and aggressive rats remain unclear.
      Here, we used c-Fos immunoreactivity to evaluate neuronal activation patterns in
      the main aggression-related areas in selected lines under basal conditions and
      after the resident-intruder (R-I) test. Although agonistic behavior of the tame
      and the aggressive rats differed significantly, social encounter caused similar
      brain activation patterns in both groups; we observed increased neuronal
      activation in the bed nucleus of stria terminalis, the hypothalamic attack area,
      and the medial amygdala 1h after the R-I test. However, neuronal activation in
      the hypothalamic attack area was significantly higher in the aggressive males
      compared to their tame counterparts. We propose that lower activation of the
      hypothalamic area is associated with the attenuation of intraspecific intermale
      aggression during selection for the elimination of aggressiveness toward humans.

PMID- 23000534
TI  - Two cognitive and neural systems for endogenous and exogenous spatial attention.
AB  - Orienting of spatial attention is a family of phylogenetically old mechanisms
      developed to select information for further processing. Information can be
      selected via top-down or endogenous mechanisms, depending on the goals of the
      observers or on the task at hand. Moreover, salient and potentially dangerous
      events also attract spatial attention via bottom-up or exogenous mechanisms,
      allowing a rapid and efficient reaction to unexpected but important events.
      Fronto-parietal brain networks have been demonstrated to play an important role
      in supporting spatial attentional orienting, although there is no consensus on
      whether there is a single attentional system supporting both endogenous and
      exogenous attention, or two anatomical and functionally different attentional
      systems. In the present paper we review behavioral evidence emphasizing the
      differential characteristics of both systems, as well as their possible
      interactions for the control of the final orienting response. Behavioral studies
      reporting qualitative differences between the effects of both systems as well as
      double dissociations of the effects of endogenous and exogenous attention on
      information processing, suggest that they constitute two independent attentional
      systems, rather than a single one. Recent models of attentional orienting in
      humans have put forward the hypothesis of a dorsal fronto-parietal network for
      orienting spatial attention, and a more ventral fronto-parietal network for
      detecting unexpected but behaviorally relevant events. Non-invasive
      neurostimulation techniques, as well as neuropsychological data, suggest that
      endogenous and exogenous attention are implemented in overlapping, although
      partially segregated, brain circuits. Although more research is needed in order
      to refine our anatomical and functional knowledge of the brain circuits
      underlying spatial attention, we conclude that endogenous and exogenous spatial
      orienting constitute two independent attentional systems, with different
      behavioral effects, and partially distinct neural substrates.

PMID- 23000535
TI  - Social status, breeding state, and GnRH soma size in convict cichlids
      (Cryptoheros nigrofasciatus).
AB  - Gonadotropin-releasing hormone (GnRH) expressing neurons in the preoptic area
      (POA) of the hypothalamus plays a key role in regulating reproductive function
      through the control of gonadotropin release. Several studies have illustrated the
      importance of the social environment in modulating the size of GnRH expressing
      neurons. In the African cichlid fish Astatotilapia burtoni, the size of the soma
      of GnRH expressing neurons in the POA varies with social status in males, and
      with breeding state in females. Territorial males have larger GnRH+ cells than
      non-territorial males, while brooder females have smaller GnRH+ cells than
      control females. The lek-like breeding system of A. burtoni is, however, only one
      type of social system within the diverse assemblage of cichlids. To gain a better
      understanding of GnRH neuronal plasticity in response to the changes in the
      social environment, we tested whether similar effects occur in the monogamous New
      World cichlid, the convict cichlid (Cryptoheros nigrofasciatus), a model species
      for the study of social behaviour. Our results indicate that, indeed GnRH
      expressing neuron soma size, and not cell number, varies with both male
      territorial status, and manipulations of female breeding state in this
      monogamous, biparental, New World cichlid.

PMID- 23000536
TI  - The neuroprotective effects of GLP-1: possible treatments for cognitive deficits
      in individuals with mood disorders.
AB  - Incretins are a group of gastrointestinal hormones detected both peripherally and
      in the central nervous system (CNS). Recent studies have documented multiple
      effects of incretins on brain structure and function. Research into the
      neurological effects of incretins has primarily focused on animal models of
      neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's and
      Parkinson's diseases). Mood disorders (e.g. bipolar disorder (BD), major
      depressive disorder (MDD)) are associated with similar alterations in brain
      structure and function, as well as a range of cognitive deficits (e.g. memory,
      learning, executive function). Brain abnormalities and cognitive deficits are
      also found in populations with metabolic disorders (e.g., diabetes mellitus Type
      2). In addition, individuals with mood disorders often have co-morbid metabolic
      conditions, thus treatment strategies which can effectively treat both cognitive
      deficits and metabolic abnormalities represent a possible integrated treatment
      avenue. In particular, glucagon-like peptide-1 (GLP-1) and its more stable,
      longer-lasting analogues have been demonstrated to exert neuroprotective and anti
      apoptotic effects, reduce beta-amyloid (Abeta) plaque accumulation, modulate long
      term potentiation and synaptic plasticity, and promote differentiation of
      neuronal progenitor cells. In animal models of behaviour, treatment with GLP-1
      receptor agonists has been demonstrated to improve measures of cognitive function
      including learning and memory, as well as reduce depressive behaviour. Available
      GLP-1 treatments also have a favourable metabolic profile which includes weight
      loss and reduced risk for hypoglycemia. Systematic evaluation of the effects of
      GLP-1 treatment in psychiatric populations who evince cognitive deficits
      represents a promising treatment avenue.

PMID- 23000538
TI  - The consequences of adolescent chronic unpredictable stress exposure on brain and
      behavior.
AB  - There is increasing evidence for adolescence as a time period vulnerable to
      environmental perturbations such as stress. What is unclear is the persistent
      nature of the effects of stress and how specific these effects are to the type of
      stressor. In this review, we describe the effects of chronic, unpredictable
      stress (CUS) exposure during adolescence on adult behavior and brain morphology
      and function in animal models. We provide evidence for adolescence as a critical
      window for the effects of physical CUS that persist into adulthood, with
      ramifications for morphological development, associated hippocampal-dependent
      tasks, and anxiety- and depressive-like behaviors. The results of this
      investigation are contrasted against those of social CUS stress exposure from the
      same time period that show reversible and, in the case of responses to drugs of
      abuse, potentially protective effects in adulthood. Finally, we discuss potential
      underlying mechanisms for these morphological and behavioral findings. It is our
      aim that the research highlighted in this review will aid in our understanding of
      the role of stress in adolescent mental health and development. This article is
      part of a Special Issue entitled: Stress, Emotional Behavior and the
      Endocannabinoid System. 

PMID- 23000537
TI  - Chronic anti-murine Abeta immunization preserves odor guided behaviors in an
      Alzheimer's beta-amyloidosis model.
AB  - Olfaction is often impaired in Alzheimer's disease (AD) and is also dysfunctional
      in mouse models of the disease. We recently demonstrated that short-term passive
      anti-murine-Abeta immunization can rescue olfactory behavior in the Tg2576 mouse
      model overexpressing a human mutation of the amyloid precursor protein (APP)
      after beta-amyloid deposition. Here we tested the ability to preserve normal
      olfactory behaviors by means of long-term passive anti-murine-Abeta immunization.
      Seven-month-old Tg2576 and non-transgenic littermate (NTg) mice were IP-injected
      biweekly with the m3.2 murine-Abeta-specific antibody until 16 mo of age when
      mice were tested in the odor habituation test. While Tg2576 mice treated with a
      control antibody showed elevations in odor investigation times and impaired odor
      habituation compared to NTg, olfactory behavior was preserved to NTg levels in
      m3.2-immunized Tg2576 mice. Immunized Tg2576 mice had significantly less beta
      amyloid immunolabeling in the olfactory bulb and entorhinal cortex, yet showed
      elevations in Thioflavin-S labeled plaques in the piriform cortex. No detectable
      changes in APP metabolite levels other than Abeta were found following m3.2
      immunization. These results demonstrate efficacy of chronic, long-term anti
      murine-Abeta m3.2 immunization in preserving normal odor-guided behaviors in a
      human APP Tg model. Further, these results provide mechanistic insights into
      olfactory dysfunction as a biomarker for AD by yielding evidence that focal
      reductions of Abeta may be sufficient to preserve olfaction.

PMID- 23000539
TI  - Effects of transcranial direct current stimulation on hemichannel pannexin-1 and
      neural plasticity in rat model of cerebral infarction.
AB  - The aim of this study was to investigate the effects of transcranial direct
      current stimulation (TDCS) on hemichannel pannexin-1 (PX1) in cortical neurons
      and neural plasticity, and explore the optimal time window of TDCS therapy after
      stroke. Adult male Sprague-Dawley rats (n=90) were randomly assigned to sham
      operation, middle cerebral artery occlusion (MCAO), and TDCS groups, and
      underwent sham operation, unilateral middle cerebral artery (MCA)
      electrocoagulation, and unilateral MCA electrocoagulation plus TDCS (daily anodal
      and cathodal 10 Hz, 0.1 mA TDCS for 30 min beginning day 1 after stroke),
      respectively. Motor function was assessed using the beam walking test (BWT), and
      density of dendritic spines (DS) and PX1 mRNA expression were compared among
      groups on days 3, 7, and 14 after stroke. Effects of PX1 blockage on DS in
      hippocampal neurons after hypoxia-ischemia were observed. TDCS significantly
      improved motor function on days 7 and 14 after stroke as indicated by reduced BWT
      scores compared with the MCAO group. The density of DS was decreased after
      stroke; the TDCS group had increased DS density compared with the MCAO group on
      days 3, 7, and 14 (all P<0.0001). Cerebral infarction induced increased PX1 mRNA
      expression on days 3, 7, and 14 (P<0.0001), and the peak PX1 mRNA expression was
      observed on day 7. TDCS did not decrease the up-regulated PX1 mRNA expression
      after stroke on day 3, but did reduce the increased post-stroke PX1 mRNA
      expression on days 7 and 14 (P<0.0001). TDCS increased the DS density after
      stroke, indicating that it may promote neural plasticity after stroke. TDCS
      intervention from day 7 to day 14 after stroke demonstrated motor function
      improvement and can down-regulate the elevated PX1 mRNA expression after stroke.

PMID- 23000541
TI  - Structure and catalytic function of sphingosine kinases: analysis by site
      directed mutagenesis and enzyme kinetics.
AB  - Sphingosine kinases 1 and 2 (SK1 and SK2) generate the bioactive lipid mediator
      sphingosine 1-phosphate and as such play a significant role in cell fate and in
      human health and disease. Despite significant interest in and examination of the
      role played by SK enzymes in disease, comparatively little is currently known
      about the three-dimensional structure and catalytic mechanisms of these enzymes.
      To date, limited numbers of studies have used site directed mutagenesis and
      activity determinations to examine the roles of individual SK residues in
      substrate, calmodulin, and membrane binding, as well as activation via
      phosphorylation. Assays are currently available that allow for both single and
      bisubstrate kinetic analysis of mutant proteins that show normal, lowered and
      enhanced activity as compared to wild type controls. Additional studies will be
      required to build on this foundation to completely understand SK mediated
      substrate binding and phosphoryl group transfer. A deeper understanding of the SK
      catalytic mechanism, as well as SK interactions with potential small molecule
      inhibitors will be invaluable to the future design and identification of SK
      activity modulators as research tools and potential therapeutics. This article is
      part of a Special Issue entitled Advances in Lysophospholipid Research.

PMID- 23000542
TI  - Reply to: very early rheumatoid arthritis as a predictor of remission: a
      multicentre real life prospective study.

PMID- 23000543
TI  - Shifting from wild to domestic hosts: the effect on the transmission of
      Trypanosoma congolense to tsetse flies.
AB  - The epidemiology and impact of animal African trypanosomosis are influenced by
      the transmissibility and the pathogenicity of the circulating trypanosome strains
      in a particular biotope. The transmissibility of 22 Trypanosoma congolense
      strains isolated from domestic and wild animals was evaluated in a total of 1213
      flies. Multivariate mixed models were used to compare infection and maturation
      rates in function of trypanosome origin (domestic or sylvatic) and pathogenicity.
      Both trypanosome pathogenicity and origin significantly affected the ability to
      establish a midgut infection in tsetse flies but not the maturation rates. The
      interaction between pathogenicity and origin was not significant. Since being
      pathogenic and having a domestic origin both increased transmissibility, dominant
      lowly pathogenic trypanosomes from domestic environments and highly pathogenic
      trypanosomes from sylvatic environments presented similar levels of
      transmissibility: 12% and 15%, respectively. Blood meals with parasite
      concentration ranging from 0.05 to 50trypanosomes/MUl blood for 3 strains of T.
      congolense were provided to different batches of tsetse flies to evaluate the
      relationship between the parasite load in blood meals and the likelihood for a
      fly to become infected. A linear relationship between parasite load and
      transmissibility was observed at low parasitaemia and a plateau was observed for
      meals containing more than 5trypanosomes/MUl. Maximum transmission was reached
      with 12.5trypanosomes/MUl blood. About 50% of the flies were refractory to T.
      congolense, whatever their concentration in the blood meal. The results suggest
      that the dose-transmissibility relationship presents a similar profile for
      different T. congolense isolates.

PMID- 23000545
TI  - Photocatalytic oxidation of indoor toluene: process risk analysis and influence
      of relative humidity, photocatalysts, and VUV irradiation.
AB  - Concentrations of 13 gaseous intermediates in photocatalytic oxidation (PCO) of
      toluene in indoor air were determined in real-time by proton transfer reaction
      mass spectrometry and desorption intensities of 7 adsorbed intermediates on the
      surface of photocatalysts were detected by temperature-programmed desorption-mass
      spectrometry. Effects of relative humidity (RH), photocatalysts, and vacuum
      ultraviolet (VUV) irradiation on the distribution and category of the
      intermediates and health risk influence index (eta) were investigated. RH
      enhances the formation rate of hydroxide radicals, leading to more intermediates
      with higher oxidation states in gas phase. N doping promotes the separation of
      photo-generated electrons and holes and enhances PCO activity accordingly. VUV
      irradiation results in higher mineralization rate and more intermediates with
      higher oxidation states and lower toxicity e.g. carboxylic acids. Health risk
      analysis indicates that higher RH, N doping of TiO(2), and VUV lead to "greener"
      intermediates and smaller eta. Finally, a conceptual diagram was proposed to
      exhibit the scenario of eta varied with extent of mineralization for various
      toxicities of inlet pollutants.

PMID- 23000544
TI  - Plasmodium falciparum populations from northeastern Myanmar display high levels
      of genetic diversity at multiple antigenic loci.
AB  - Levels of genetic diversity of the malaria parasites and multiclonal infections
      are correlated with transmission intensity. In order to monitor the effect of
      strengthened malaria control efforts in recent years at the China-Myanmar border
      area, we followed the temporal dynamics of genetic diversity of three polymorphic
      antigenic markers msp1, msp2, and glurp in the Plasmodium falciparum populations.
      Despite reduced malaria prevalence in the region, parasite populations exhibited
      high levels of genetic diversity. Genotyping 258 clinical samples collected in
      four years detected a total of 22 PCR size alleles. Multiclonal infections were
      detected in 45.7% of the patient samples, giving a minimum multiplicity of
      infection of 1.41. The majority of alleles experienced significant temporal
      fluctuations through the years. Haplotype diversity based on the three-locus
      genotypes ranged from the lowest in 2009 at 0.33 to the highest in 2010 at 0.80.
      Sequencing of msp1 fragments from 36 random samples of five allele size groups
      detected 13 different sequences, revealing an additional layer of genetic
      complexity. This study suggests that despite reduced prevalence of malaria
      infections in this region, the parasite population size and transmission
      intensity remained high enough to allow effective genetic recombination of the
      parasites and continued maintenance of genetic diversity.

PMID- 23000546
TI  - Response of the common cutworm Spodoptera litura to zinc stress: Zn accumulation,
      metallothionein and cell ultrastructure of the midgut.
AB  - By exposing the common cutworm Spodoptera litura Fabricius larvae to a range of
      Zinc (Zn) stress, we investigated the effects of dietary Zn on Zn accumulation,
      metallothionein (MT), and on the ultrastructure of the midgut. The techniques we
      used were inductively coupled plasma-atomic emission spectrometer (ICP-AES), real
      time PCR combined with cadmium-hemoglobin total saturation, and transmission
      electron microscopy (TEM), respectively. There was a significant dose-response
      relationship between the Zn accumulations in the midgut of the larvae and the Zn
      concentrations in the diet. Furthermore, both MT content and MT gene expression
      in the midgut were significantly induced in the 50-500 mg Zn/kg treatments, and
      were significantly positively correlated with the Zn accumulations in the midgut.
      When S. litura larvae were fed with the diet treated with 500 mg Zn/kg, Zn
      accumulation and MT content in the midgut was 4450.85 mg Zn/kg and 372.77 mg/kg,
      respectively, thereafter there was a little increase; the level of MT gene
      expression was maximal, thereafter there was a sharp decrease. TEM showed that
      numerous electron-dense granules (EDGs) and vacuoles appeared in the cytoplasm of
      the midgut cells, their number and size being closely correlated with the Zn
      accumulations in the midgut. Moreover, the nuclei were strongly influenced by Zn
      stress, evidenced by chromatin condensation and irregular nuclear membranes.
      Therefore, after being exposed to Zn in the threshold (500 mg Zn/kg) range, S.
      litura larvae could accumulate Zn in the midgut, which led to the induction of MT
      and changes in cell ultrastructure (mainly the presence of EDGs). The induction
      of MT and precipitation of Zn in EDGs may be the effective detoxification
      mechanisms by which the herbivorous insect S. litura defends itself against heavy
      metals.

PMID- 23000547
TI  - Pig slurry and mineral fertilization strategies' effects on soil quality:
      macroaggregate stability and organic matter fractions.
AB  - Applying pig slurry to the land as fertilizer at appropriate agronomic rates is
      important to close nutrient cycles and optimize the value of organic matter.
      However a long-term discussion has taken place about its effects on soil quality.
      In the north-east of Spain, eight fertilization strategies were evaluated on the
      soil quality parameters' aggregate stability, soil organic matter (SOM) physical
      fractions and soil microbial biomass (SMB). Six strategies used different pig
      slurries (PS) which provided organic matter from 1.7 to 2.6 t ha(-1)yr(-1), the
      rest (mineral N fertilization and a control) did not. Pig slurries were applied
      at sowing and/or at cereal tillering, as sidedressing. Field experiments were
      maintained for an 8-year period, in a silty loam soil devoted to a rainfed winter
      cereal. Soil samples were taken once, before the last sidedressing in 2011.
      Aggregate stability was quantified using the standard water-stable aggregate
      method but including a modification which meant that pre-wetting was avoided
      (WSA(MOD)). When using the WSA(MOD) method, we found a tendency for the
      percentage of water-stable aggregates to increase due to PS application
      (differences of up to 74% in the increment) and it was more marked the nearer
      they were measured to the application time (3 months vs. 12 months). The
      strategies which include PS show a positive effect on the SOM amount, mainly in
      the 0.05-0.2 mm light fraction, which increased by up to 34% with every 10 t ha(
      1) organic C applied, and on SMB (up to 53% increment). There is a positive and
      significant linear relationship (p < 0.05, R(2) = 0.75) between the SOM light
      fraction (%) and the water-stable aggregates soil content (%, WSA(MOD)). Thus,
      the introduction of PS in fertilization strategies improves soil quality
      parameters. However, the soil quality benefits need to be balanced with any other
      potential environmental impact.

PMID- 23000548
TI  - The complexity of nanoparticle dissolution and its importance in
      nanotoxicological studies.
AB  - Dissolution of nanoparticles (NPs) is an important property that alters their
      abundance and is often a critical step in determining safety of nanoparticles.
      The dissolution status of the NPs in exposure media (i.e. whether they remain in
      particulate form or dissolve - and to what extent), strongly affects the uptake
      pathway, toxicity mechanisms and the environmental compartment in which NPs will
      have the highest potential impact. A review of available dissolution data on NPs
      demonstrates there is a range of potential outcomes depending on the NPs and the
      exposure media. For example two nominally identical nanoparticles, in terms of
      size and composition, could have totally different dissolution behaviours,
      subject to different surface modifications. Therefore, it is imperative that
      toxicological studies are conducted in conjunction with dissolution of NPs to
      establish the true biological effect of NPs and hence, assist in their
      regulation.

PMID- 23000549
TI  - The effect of the indoor environment on the fate of organic chemicals in the
      urban landscape.
AB  - To assess the effect of the indoor environment on the urban fate of organic
      chemicals, an 8-compartment indoor-inclusive steady state multimedia chemical
      fate model was developed. The model includes typical urban compartments (air,
      soil, water, sediment, and urban film) and a novel module representing a generic
      indoor environment. The model was parameterized to the municipality of Stockholm,
      Sweden and applied to four organic chemicals with different physical-chemical
      characteristics and use patterns: formaldehyde, 2,4,6-tribromophenol, di
      ethylhexylphthalate and decabromodiphenyl ether. The results show that emissions
      to indoor air may increase the steady state mass and residence time in the urban
      environment by a factor of 1.1 to 22 for the four chemicals, compared to if
      emissions are assigned to outdoor air. This is due to the nested nature of the
      indoor environment, which creates a physical barrier that prevents chemicals from
      leaving the urban system with outflowing air. For DEHP and BDE 209, the
      additional partitioning to indoor surfaces results in a greater importance of the
      indoor removal pathways from surfaces. The outdoor environmental concentrations
      of these chemicals are predicted to be lower if emitted to indoor air than if
      emitted to outdoor air because of the additional indoor removal pathways of dust
      and indoor film, leading to loss of chemical from the system. For formaldehyde
      and 2,4,6-TBP outdoor environmental concentrations are not affected by whether
      the release occurs indoors or outdoors because of the limited partitioning to
      indoor surfaces. A sensitivity analysis revealed that there appears to be a
      relationship between logK(OA) and the impact of the ventilation rate on the urban
      fate of organic chemicals.

PMID- 23000550
TI  - Soil radiocesium distribution in rice fields disturbed by farming process after
      the Fukushima Dai-ichi Nuclear Power Plant accident.
AB  - A magnitude 9.0 earthquake and subsequent large tsunami hit the northeastern
      coast of Japan on March 11, 2011. This resulted in serious damage to the reactors
      of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), operated by the Tokyo
      Electric Power Company. Large amounts of radionuclides were released from the
      FDNPP, a proportion of which were deposited onto the ground. In this study, we
      investigated soil radiocesium contamination of rice fields in Aga and
      Minamiuonuma, Niigata, ~130 and 200 km away from the FDNPP, respectively, as
      Niigata is one of the largest rice growing regions in Japan. Soil samples were
      collected from the plow layer of five rice fields in August and September, 5-6
      months after the FDNPP accident. Results showed that radiocesium concentrations
      (the sum of Cs-134 and Cs-137) in the rice soil samples were ~300 Bq (kg dry
      soil)(-1). All samples contained a Cs-134/Cs-137 activity ratio of 0.68-0.96
      after correction to March 11, 2011, showing that the radiocesium released from
      the FDNPP were deposited on these areas. Although the rice fields had been
      disturbed by farming processes after the FDNPP accident, the depth distribution
      of radiocesium concentrations in the plow layers showed higher concentrations in
      the upper soil layers. This suggests that spring tillage, flooding and puddling
      performed before rice transplantation may not disperse radiocesium deposited on
      the surface through the whole plow layer. In addition, the planar distribution of
      radiocesium concentrations was examined near the water inlet in one of the rice
      fields. Highest activities were found aligned with the direction of irrigation
      water discharge, indicating that radioactivity levels in rice fields may be
      elevated by an influx of additional radionuclides, probably in irrigation water,
      during farming.

PMID- 23000551
TI  - Dimensionality reduced cortical features and their use in the classification of
      Alzheimer's disease and mild cognitive impairment.
AB  - Features defined on the cortical surface derived from magnetic resonance imaging
      provide important information to distinguish normal controls from Alzheimer's
      disease (AD) and mild cognitive impairment (MCI). We adopted cortical thickness
      and sulcal depth, parameterized by three dimensional meshes, as our feature. The
      cortical feature is high dimensional and direct use of it is problematic in a
      modern classifier due to small sample size problem. We applied manifold learning
      to reduce the dimensionality of the feature and then tested the usage of the
      dimensionality reduced feature with a support vector machine classifier. A leave
      one-out cross-validation was adopted for quantifying classifier performance. We
      chose principal component analysis (PCA) as the manifold learning method. We
      applied PCA to a region of interest within the cortical surface. Our
      classification performance was at least on par for the AD/normal and MCI/normal
      groups and significantly better for the AD/MCI groups compared to recent studies.
      Our approach was tested using 25 AD, 25 MCI, and 50 normal control patients from
      the OASIS database.

PMID- 23000552
TI  - Lying in the scanner: localized inhibition predicts lying skill.
AB  - Recent literature suggests that lying may be revealed by elevated cognitive
      effort. A functional magnetic resonance imaging experiment using a match-mismatch
      detection task was conducted that found support for this hypothesis in two ways.
      First, compared to truthful reporting, lying (i.e., responding that matches were
      mismatches or vice versa) triggered greater activation of the working memory
      network in the brain. This was especially true for lying about a match, where
      activation in the WM network was found to be greater than when lying about a
      mismatch. Lying also activated the right rostrolateral prefrontal cortex (BA 10)
      a key cognitive control region that regulates the interplay between stimulus
      oriented and internally-generated schemas. Second, activation in the right
      inferior frontal gyrus (BA 44) - a brain region underpinning inhibition -
      predicted lying skill. The findings show that the neural correlates of cognitive
      effort and control can be used to detect lying, and that a specific neural marker
      of inhibition can predict how well one lies.

PMID- 23000553
TI  - Increased expression of interleukin-18 in the trigeminal spinal subnucleus
      caudalis after inferior alveolar nerve injury in the rat.
AB  - Interleukin-18 (IL-18) is an important regulator of innate and immune responses,
      and is known to be expressed in various types of cells and upregulated in
      pathological conditions including tissue injury and inflammation, suggesting it
      has both proinflammatory and compensatory roles. Here we show that IL-18 was
      increased in microglia in the trigeminal spinal subnucleus caudalis (Vc) after
      peripheral nerve injury. We used a trigeminal neuropathic pain model in which the
      withdrawal threshold of maxillary whisker pad skin was significantly decreased
      after inferior alveolar nerve transection, and observed a striking increase in IL
      18 expression in the Vc around the obex area from 3d and continued until 14d
      after nerve injury. The IL-18 labeled cells were largely colocalized with Iba1,
      suggesting this upregulation occurred in hyperactive microglia. We also found
      that the IL-18 induction coexisted with phosphorylated p38 MAPK, indicating a
      possible role of p38 in the regulation of IL-18. Our findings are the first
      report that injury of trigeminal nerve induced IL-18 upregulation in activated
      microglia in the Vc, suggesting a possible role of IL-18 in orofacial neuropathic
      pain.

PMID- 23000554
TI  - HIPK2 kinase activity depends on cis-autophosphorylation of its activation loop.
AB  - The multitude of mechanisms regulating the activity of protein kinases includes
      phosphorylation of amino acids contained in the activation loop. Here we show
      that the serine/threonine kinase HIPK2 (homeodomain-interacting protein kinase 2)
      is heavily modified by autophosphorylation, which occurs by cis
      autophosphorylation at the activation loop and by trans-autophosphorylation at
      other phosphorylation sites. Cis-autophosphorylation of HIPK2 at Y354 and S357 in
      the activation loop is essential for its kinase function and the binding to
      substrates and the interaction partner Pin1. HIPK2 activation loop
      phosphorylation is also required for its biological activity as a regulator of
      gene expression and cell proliferation. Phosphorylation of HIPK2 at Y354 alone is
      not sufficient for full HIPK2 activity, which is in marked contrast to some dual
      specificity tyrosine-phosphorylated and regulated kinases where tyrosine
      phosphorylation is absolutely essential. This study shows that differential
      phosphorylation of HIPK2 provides a mechanism for controlling and specifying the
      signal output from this kinase.

PMID- 23000555
TI  - Plasmodium falciparum: the potential of the cancer chemotherapeutic agent
      cisplatin and its analogues as anti-malarials.
AB  - The anti-malarial activity of the cancer chemotherapeutic agent cisplatin and
      cisplatin analogues was determined in Plasmodium falciparum. The cisplatin
      analogues included DNA-targeted acridine-tethered platinum compounds, carboplatin
      and transplatin. A [(3)H]-hypoxanthine incorporation assay was utilised to
      determine the IC(50) of cisplatin and related analogues. The DNA-targeted Pt
      compounds and cisplatin were shown to have IC(50) values that were less than 1
      MUM in P. falciparum, with the acridine-tethered compounds having the greatest
      cytotoxicity. Carboplatin and transplatin had IC(50) values of 12 and 16 MUM,
      respectively. The outcome for transplatin was particularly interesting since it
      is not cytotoxic in mammalian cells. These results were discussed with respect to
      the potential use of cisplatin and cisplatin analogues as anti-malarial agents.

PMID- 23000557
TI  - Exploring health information technology education: an analysis of the research.
AB  - This article is an analysis of the Health Information Technology Education
      published research. The purpose of this study was to examine selected literature
      using variables such as journal frequency, keyword analysis, universities
      associated with the research and geographic diversity. The analysis presented in
      this paper has identified intellectually significant studies that have
      contributed to the development and accumulation of intellectual wealth of Health
      Information Technology. The keyword analysis suggests that Health Information
      Technology research has evolved from establishing concepts and domains of health
      information systems, technology and management to contemporary issues such as
      education, outsourcing, web services and security. The research findings have
      implications for educators, researchers, journal.

PMID- 23000556
TI  - Cloning, sequencing and phylogenetic analysis of the small GTPase gene cdc-42
      from Ancylostoma caninum.
AB  - CDC-42 is a member of the Rho GTPase subfamily that is involved in many signaling
      pathways, including mitosis, cell polarity, cell migration and cytoskeleton
      remodeling. Here, we present the first characterization of a full-length cDNA
      encoding the small GTPase cdc-42, designated as Accdc-42, isolated from the
      parasitic nematode Ancylostoma caninum. The encoded protein contains 191 amino
      acid residues with a predicted molecular weight of 21 kDa and displays a high
      level of identity with the Rho-family GTPase protein CDC-42. Phylogenetic
      analysis revealed that Accdc-42 was most closely related to Caenorhabditis
      briggsae cdc-42. Comparison with selected sequences from the free-living nematode
      Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, Danio rerio, Mus
      musculus and human genomes showed that Accdc-42 is highly conserved. AcCDC-42
      demonstrates the highest identity to CDC-42 from C. briggsae (94.2%), and it also
      exhibits 91.6% identity to CDC-42 from C. elegans and 91.1% from Brugia malayi.
      Additionally, the transcript of Accdc-42 was analyzed during the different
      developmental stages of the worm. Accdc-42 was expressed in the L1/L2 larvae, L3
      larvae and female and male adults of A. caninum.

PMID- 23000558
TI  - Surveys assessing STI related health information needs of adolescent population.
AB  - Individuals are widely using different sources to acquire health information. To
      better understand the adolescents' needs of having tailored health information,
      it becomes important to assess the existing sources that they utilize to obtain
      that information. Our study objective was to identify sources of STI related
      health information studied among adolescents. A search was conducted using Google
      during November 2011 to January 2012 to identify different STI related health
      information sources. A combination of 3 key words including adolescent sexual
      health survey, sex health information survey, and sexual health education
      assessment were used. The first 20 weblinks from each search were combined
      resulting in a total of 60 primary weblinks. Secondary search was conducted to
      identify additional relevant articles. A total of 10 articles were found
      relevant, of which 52% were non US-based. 87% of the primary articles were
      excluded as they did not gather the source of STI related health information in
      their surveys. Most common sources assessed were TV, doctor, books, magazines,
      friends, and parents. Internet was assessed only in 3 of the final 10 articles.
      Future research should be done to assess role of internet as a possible source of
      disseminating STI related health information among adolescents.

PMID- 23000559
TI  - A comparative study of pattern recognition classifiers to predict physical
      activities using smartphones and wearable body sensors.
AB  - This paper presents a wireless body area network platform that performs physical
      activities recognition using accelerometers, biosignals and smartphones. Multiple
      classifiers and sensor combinations were examined to identify the classifier with
      the best recognition performance for the static and dynamic activities. The
      Functional Trees classifier proved to provide the best results among the
      classifiers evaluated (Naive Bayes, Bayesian Networks, Support Vector Machines
      and Decision Trees [C4.5, Random Forest]) and was used to train the model which
      was implemented for the real time activity recognition on the smartphone. The
      identified patterns of daily physical activities were used to examine conformance
      with medical advice, regarding physical activity guidelines. An algorithm based
      on Skip Chain Conditional Random Fields, received as inputs the recognized
      activities and data retrieved from the GPS receiver of the smartphone to develop
      dynamic daily patterns that enhance prediction results. The presented platform
      can be extended to be used in the prevention of short-term complications of
      metabolic diseases such as diabetes.

PMID- 23000560
TI  - Duration discretisation for activity recognition.
AB  - Activity recognition has become a key component within smart environments that
      aim at providing assistive solutions for their users. Learning high level
      activities from low level sensor data depends on several parameters, one of which
      is the duration of the activities themselves. Nevertheless, directly
      incorporating continuous duration values into a model is a complex process and
      may not prove to be very qualitative. In this paper we aim at discretising
      activity related durations using different clustering algorithms. We explore the
      possibility of discretising duration data through the use of rudimentary
      clustering algorithms such as visual inspection to more established methods such
      as model based clustering. In addition, a probabilistic model is built that
      predicts both person and activities from the observed values of sensor sequence,
      time and discrete duration values. Each of the models created is compared in
      terms of its performance in the prediction of activities. Following analysis of
      the results attained it has been found that irrespective of the clustering
      algorithm used for duration discretisation, incorporating the duration
      information increases the prediction performance. Prediction accuracy was
      improved by almost 3% when the model was built incorporating durations.

PMID- 23000561
TI  - Minipig urethra: a suitable animal model in vitro.
AB  - The study demonstrates that the minipig urethra is an appropriate animal model
      for in vitro experiments and therefore promising for long-term animal tests of
      artificial urinary sphincter systems in vivo. Freshly explanted porcine and
      minipig urethras were connected to a fluid reservoir that simulated the bladder
      pressure. This bladder pressure was adjusted by changing the water level
      (hydrostatic pressure). Specially designed aluminum sphincters loaded with a
      fluid-filled container were used to close/open the urethras. Results from
      minipigs and domestic pigs were compared to data published for human urethras. We
      measured the leak-point pressures (LPP) by adjusting the bladder pressure at a
      constant sphincter length and by changing the sphincter length at a constant
      bladder pressure. Because the urethral tissue shows visco-elastic behavior, LPPs
      for both opening and closing were measured. By fitting the in vitro data, we
      evaluated the three characteristic parameters from the empirical urethra
      compression model, i.e. wall pressure < pW >opening = -(12.9 +/- 0.9) cmH2O, < pW
      >closing = (8.6 +/- 1.1) cmH2O, < FR >opening = (0.06 +/- 0.02) N, < FR >closing
      = (0.10 +/- 0.02) N, < LR >opening = (3.0 +/- 0.3) mm, < LR >closing = (5.1 +/-
      0.3) mm,and (male) minipig urethras:< pW >opening = -(13.4 +/- 0.3) cmH2O, < pW
      >closing = -(8.6 +/- 0.4) cmH2O,< FR >opening = (0.19 +/- 0.01) N, < FR >closing
      = (0.21 +/- 0.02) N,< LR >opening = (2.4 +/- 0.1) mm, < LR >closing = (3.3 +/-
      1.0) mm. These {?it in vitro} tests quantified by means of the urethra
      compression model demonstrate that the minipig (especially the male one)
      represents a suitable animal model for testing artificial urinary sphincters.

PMID- 23000562
TI  - Characterization and meiotic segregation of a supernumerary marker chromosome in
      sperm of infertile males: case report and literature review.
AB  - This couple presented with a 4-year history of primary infertility. The male
      partner was found to have oligoasthenozoospermia. A supernumerary marker
      chromosome (SMC) was found. Fluorescent in situ hybridization (FISH) analyses
      showed that the SMC was a heterochromatic dicentric marker derived from
      chromosome 22. Further FISH procedures showed the rate of unbalanced spermatozoa
      containing one chromosome 22 and the SMC to be 15.6%. Due to the low risk of
      fetal chromosomal imbalance linked to the paternal SMC and the risk of
      miscarriage linked to the amniocentesis, the couple declined prenatal diagnosis.
      A healthy newborn baby was obtained after ICSI.

PMID- 23000563
TI  - Efficacy of endovascular stroke management in elderly patients.

PMID- 23000564
TI  - Stent assisted embolization of 64 anterior communicating artery aneurysms.
AB  - INTRODUCTION: Anterior communicating artery (ACoA) aneurysms comprised over half
      of the ruptured aneurysms in the International Subarachnoid Trial. Endovascular
      treatment of ACoA aneurysms has provided good results, but until the introduction
      of intracranial stents, many ACoA aneurysms could not be treated without
      craniotomy. The current study analyzes the results of ACoA aneurysm treatment
      using stent assisted embolization. METHODS: 64 patients with ACoA aneurysms
      underwent stent assisted aneurysm repair. Four were treated in the acute rupture
      phase and a fifth ruptured aneurysm was stented in a second procedure after
      initial coiling. Five aneurysms were 10 mm or more in greatest diameter. Follow
      up angiography was performed 6 months after treatment; then, patients were
      followed with annual MR angiography. Technical, clinical, and long term
      radiographic results were analyzed. RESULTS: Stents were successfully deployed in
      each case. One patient was eventually treated with a three stent construct and
      died of perioperative hemorrhage. One major stroke occurred during a separate
      procedure when a patient was taken off antiplatelet medications. These cases were
      the only aneurysm related morbidity (1.6%) and mortality (1.6%) events during the
      entire follow-up period. After stent assisted embolization, 32 (50.0%) ACoA
      aneurysms were completely occluded, 15 (23.4%) had residual neck, and 17 (26.6%)
      had residual filling. At first radiographic follow-up, 39 of 55 (70.9%) showed
      complete occlusion. Three (5.5%) total aneurysms required retreatment.
      CONCLUSIONS: Stent assisted aneurysm treatment was a safe and effective option in
      this series of ACoA aneurysms with maximum diameter less than 15 mm. ACoA
      aneurysms may be more likely to recur regardless of treatment option, but stent
      assisted embolization may be durable after stable initial radiographic follow-up.

PMID- 23000565
TI  - Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and
      rheumatoid arthritis.
AB  - We sought to determine the frequency of I/D polymorphism genotypes of angiotensin
      converting enzyme gene in Turkish patients with rheumatoid arthritis. Genomic DNA
      obtained from 256 individuals (110 patients with rheumatoid arthritis and 146
      healthy controls) was used in the study. ACE gene I/D polymorphism genotypes were
      determined using polymerase chain reaction using I and D allele-specific primers.
      There was a statistically significant difference between the groups with respect
      to genotype distribution (p=0.001). A significant difference was found in
      frequencies of ACE I/D alleles between patients and controls, with RA patients
      having a higher representation of D and lower representation of I alleles
      compared to controls (p<0.001). As a result of our study, angiotensin converting
      enzyme gene I/D polymorphism DD genotype could be a genetic marker in rheumatoid
      arthritis in the Turkish study population.

PMID- 23000566
TI  - HLA class I allele frequencies in the Lebanese population.
AB  - The highly polymorphic Human Leukocyte Antigen system encompasses different loci
      that have been studied in transplantation as well as diseases and population
      associated research. This study is the first and largest of its kind to describe
      the distribution of HLA-A, -B and -C alleles in Lebanon. Respectively, 1994, 1309
      and 1163 Lebanese individuals referred for HLA typing and possible bone
      marrow/kidney donation were tested for HLA-A, HLA-B and HLA-C alleles using the
      polymerase chain reaction/Sequence specific priming (PCR-SSP) method. Our data
      were compared to that of several populations with interesting and common findings
      shared with the Moroccan, Jordanian, Tunisian, Omani, Korean, Chinese, Japanese,
      Peruan, Bulgarian, Irish, Polish, Spanish, Swiss, American, African and Brazilian
      populations. The following data concerning the Lebanese population will help
      future investigators to study the relation of HLA-A, -B and -C alleles with
      common diseases in Lebanon and will add to the available international
      literature. This new data will serve as a major reference report in the region.

PMID- 23000567
TI  - Autonomic regulation predicts performance on Wisconsin Card Sorting Test (WCST)
      in adults with schizophrenia.
AB  - Although executive functions have been associated with autonomic regulatory
      capacity in healthy adults, there appear to be no reports of these relations in
      adults with schizophrenia to date. We tested whether baseline autonomic
      regulation was associated with performance on the Wisconsin Card Sorting Test
      (WCST) in a group of 42 stable community outpatients with schizophrenia. Patients
      exhibited faster resting heart rates and lower respiratory sinus arrhythmia (RSA)
      than age-matched controls, consistent with previous research. Patients also
      completed relatively few WCST categories and made many perseverative errors,
      replicating prior studies. Within the patient group, relatively better WCST
      performance was associated with slower resting heart rate and higher RSA,
      suggesting that inefficient executive and autonomic functioning in schizophrenia
      may be linked. WCST performance and autonomic regulatory capacity were further
      reduced in a subset of patients receiving clozapine, but relations between WCST
      performance and autonomic regulatory parameters did not differ from those of
      other patients. Findings extend the neurovisceral integration model of autonomic
      regulation to adults with schizophrenia and attest to the reliability of the
      model.

PMID- 23000568
TI  - Effects of pre-sleep simulated on-call instructions on subsequent sleep.
AB  - Nightly interventions, prevalent to on-call situations, can have negative
      consequences for those involved. We investigated if intervention-free-on-call
      nights would also mean disturbance-free-sleep for people on-call. 16 healthy
      sleepers spent three nights in the laboratory: after a habituation night,
      reference and on-call night were counterbalanced. Subjects were instructed to
      react to a sound, presented at unpredictable moments during the night.
      Participants were unaware of the fact that the sound would never be presented.
      These vigilance instructions resulted in more subjective wake after sleep onset
      (WASO), lower subjective sleep efficiency and significantly lower experienced
      sleep quality. Objectively, a longer sleep onset, an increased amount of WASO and
      significantly lower sleep efficiency were observed. During deep sleep,
      significantly more beta activity was recorded. Apart from real nightly
      interventions increased vigilance during the night causes sleep to be less
      efficient and less qualitative as shown by an increase in wake-activity and a
      distorted sleep perception.

PMID- 23000569
TI  - How long does flash-heated breast milk remain safe for a baby to drink at room
      temperature?

PMID- 23000570
TI  - Cardiac tamponade due to fatal pneumopericardium after commercial flight:
      transportation of a premature infant with chronic lung disease.
AB  - We report a case of cardiac tamponade due to air leak and fatal pneumopericardium
      that occurred after commercial flight transportation of a premature infant with
      chronic lung disease without respiratory distress. We review and discuss aspects
      of flight pathophysiology, and conclude that careful preparation before, and
      close monitoring during, commercial flight transportation is necessary for
      premature infants.

PMID- 23000571
TI  - Versatile characterization of thiol-functionalized printed metal electrodes on
      flexible substrates for cheap diagnostic applications.
AB  - BACKGROUND: Cheap, reliable, point-of-care diagnostics is a necessity for the
      growing and aging population of the world. Paper substrate and printing method,
      combined together, are the cheapest possible method for generating high-volume
      diagnostic sensor platforms. Electrical transduction tools also minimize the cost
      and enhance the simplicity of the devices. METHODS: Standard surface
      characterization techniques, namely contact angle measurements, atomic force
      microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) were used to analyze
      the growth of the organic thiol layers on top of the printed metal electrodes on
      paper substrates. The results were compared with those obtained by impedimetric
      electrical characterization method. RESULTS: This article reports the fabrication
      and characterization of printed metal electrodes and their functionalization by
      organic layers on paper and plastic substrates for biosensing and diagnostic
      applications. Impedimetric measurement is proposed as a simple, yet elegant,
      method of characterization of the organic layer growth. CONCLUSIONS: Very good
      correlation was observed between the results of organic layer growth from
      different measurement methods, justifying the use of paper as a substrate,
      printing as a method for fabricating metal and organic layers and impedance as a
      suitable measurement method for hand-held diagnostic devices. GENERAL
      SIGNIFICANCE: This result paves the way for the fabrication of more advanced bio
      recognition layers for bio-affinity sensors using a printing technology that is
      compatible with flexible and cheap paper substrates. This article is part of a
      Special Issue entitled Organic Bioelectronics - Novel Applications in
      Biomedicine.

PMID- 23000572
TI  - A pentapeptide signature motif plays a pivotal role in Leishmania DNA
      topoisomerase IB activity and camptothecin sensitivity.
AB  - BACKGROUND: Leishmania donovani - the causative agent of visceral leishmaniasis -
      has several evolutionary characteristics that make the disease difficult to
      combat. Among these differences, a rare heterodimeric DNA topoisomerase IB has
      been reported thus opening a new promising field in the therapy of leishmaniasis.
      Several studies of the human enzyme have pointed to the importance of the linker
      domain in respect to camptothecin sensitivity. At present, it has been impossible
      to pinpoint the regions that make up the linker domain in Leishmania. METHODS:
      Several site-directed mutations as well as internal and linear truncations
      involving both subunits were assayed on both, relaxation activity and sensitivity
      to camptothecin. RESULTS: Truncations performed on the trypanosomatids conserved
      motif (RPPVVRS) of the small subunit of leishmanial DNA topoisomerase IB
      demonstrated that elimination of pentapeptide RPPVV produced a nonfunctional
      enzyme. However, the removal of the dipeptide RS led to an enzyme with reduced
      relaxation activity and less sensitivity to camptothecin. The basic structure,
      both sensitive to camptothecin and able to fully relax DNA, composed of amino
      acids 1-592 and 175-262 in the large and small subunits, respectively.
      CONCLUSION: It has been established that the region between amino acids 175 and
      180 (RPPVV) of the small subunit plays a pivotal role in both interaction with
      the large subunit and sensitivity to camptothecin in Leishmania. GENERAL
      SIGNIFICANCE: The present report describes a functional analysis of the
      leishmanial DNA topoisomerase IB regions directly involved both in sensitivity to
      poisons and in the conformation of the linker domain.

PMID- 23000573
TI  - Porphyrin binding mechanism is altered by protonation at the loops in G
      quadruplex DNA formed near the transcriptional activation site of the human c-kit
      gene.
AB  - BACKGROUND: G-quadruplex DNA structures are hypothesized to be involved in the
      regulation of gene expression and telomere homeostasis. The development of small
      molecules that modulate the stability of G-quadruplex structures has a potential
      therapeutic interest in cancer treatment and prevention of aging. METHODS:
      Molecular absorption and circular dichroism spectra were used to monitor thermal
      denaturation, acid base titration and mole ratio experiments. The resulting data
      were analyzed by multivariate data analysis methods. Surface plasmon resonance
      was also used to probe the kinetics and affinity of the DNA-drug interactions.
      RESULTS: We investigated the interaction between a G-quadruplex-forming sequence
      in the human c-kit proto-oncogene and the water soluble porphyrin TMPyP4. The
      role of cytosine and adenine residues at the loops of G-quadruplex was studied by
      substitution of these residues by thymidines. CONCLUSIONS: Here, we show the
      existence of two binding modes between TMPyP4 and the considered G-quadruplex.
      The stronger binding mode (formation constant around 107) involves end-stacking,
      while the weaker binding mode (formation constant around 106) is probably due to
      external loop binding. Evidence for the release of TMPyP4 upon protonation of
      bases at the loops has been observed. GENERAL SIGNIFICANCE: The results may be
      used for the design of porphyrin-based anti-cancer molecules with a higher
      affinity to G-quadruplex structures which may have anticancer properties.

PMID- 23000574
TI  - Expression of glycogenes in differentiating human NT2N neurons. Downregulation of
      fucosyltransferase 9 leads to decreased Lewis(x) levels and impaired neurite
      outgrowth.
AB  - BACKGROUND: Several glycan structures are functionally relevant in biological
      events associated with differentiation and regeneration which occur in the
      central nervous system. Here we have analysed the glycogene expression and
      glycosylation patterns during human NT2N neuron differentiation. We have further
      studied the impact of downregulating fucosyltransferase 9 (FUT9) on neurite
      outgrowth. METHODS: The expression of glycogenes in human NT2N neurons
      differentiating from teratocarcinoma NTERA-2/cl.D1 cells has been analysed using
      the GlycoV4 GeneChip expression microarray. Changes in glycosylation have been
      monitored by immunoblot, immunofluorescence microscopy, HPLC and MALDI-TOF MS.
      Peptide mass fingerprinting and immunoprecipitation have been used for protein
      identification. FUT9 was downregulated using silencing RNA. RESULTS AND
      CONCLUSIONS: One hundred twelve mRNA transcripts showed statistically significant
      up-regulation, including the genes coding for proteins involved in the synthesis
      of the Lewis(x) motif (FUT9), polysialic acid (ST8SIA2 and ST8SIA4) and HNK-1
      (B3GAT2). Accordingly, increased levels of the corresponding carbohydrate
      epitopes have been observed. The Lewis(x) structure was found in a carrier
      glycoprotein that was identified as the CRA-a isoform of human neural cell
      adhesion molecule 1. Downregulation of FUT9 caused significant decreases in the
      levels of Lewis(x), as well as GAP-43, a marker of neurite outgrowth.
      Concomitantly, a reduction in neurite formation and outgrowth has been observed
      that was reversed by FUT9 overexpression. GENERAL SIGNIFICANCE: These results
      provided information about the regulation of glycogenes during neuron
      differentiation and they showed that the Lewis(x) motif plays a functional role
      in neurite outgrowth from human neurons.

PMID- 23000575
TI  - Enhancement in selective mitochondrial association by direct modification of a
      mitochondrial targeting signal peptide on a liposomal based nanocarrier.
AB  - The focus of this study was on the development of a nano carrier targeted to
      mitochondria, a promising therapeutic drug target. We synthesized a lipid
      derivative that is conjugated with a mitochondrial targeting signal peptide
      (MTS), which permits the selective delivery of certain types of proteins to
      mitochondria. We then explored the use of an innovative technology in which MTS
      and the MITO-Porter were integrated. The latter is a liposome that delivers
      cargos to mitochondria via membrane fusion. The results indicate that the
      combination of MTS and the MITO-Porter would be useful for selective
      mitochondrial delivery via membrane fusion. 

PMID- 23000576
TI  - Characterization of a glycerophosphodiesterase with an unusual tripartite
      distribution and an important role in the asexual blood stages of Plasmodium
      falciparum.
AB  - Catabolism of glycerophospholipids during the rapid growth of the asexual
      intraerythrocytic malaria parasite may contribute to membrane recycling and the
      acquisition of lipid biosynthetic precursors from the host. To better understand
      the scope of lipid catabolism in Plasmodium falciparum, we have characterized a
      malarial homolog of bacterial glycerophosphodiesterases. These enzymes catalyze
      the hydrolysis of glycerophosphodiesterases that are generated by phospholipase
      catalyzed removal of the two acyl groups from glycerophospholipids. The P.
      falciparum glycerophosphodiesterase (PfGDPD) exhibits an unusual tripartite
      distribution during the asexual blood stage with pools of enzyme in the
      parasitophorous vacuole, food vacuole and cytosol. Efforts to disrupt the
      chromosomal PfGDPD coding sequence were unsuccessful, which implies that the
      enzyme is important for efficient parasite growth. Tagging of the endogenous pool
      of PfGDPD with a conditional aggregation domain partially perturbed the
      distribution of the enzyme in the parasitophorous vacuole but had no discernable
      effect on growth in culture. Kinetic characterization of the hydrolysis of
      glycerophosphocholine by recombinant PfGDPD, an Mg(2+)-dependent enzyme, yielded
      steady-state parameters that were comparable to those of a homologous bacterial
      glycerophosphodiesterase. Together, these results suggest a physiological role
      for PfGDPD in glycerophospholipid catabolism in multiple subcellular
      compartments. Possibilities for what this role might be are discussed.

PMID- 23000577
TI  - Tissue distribution of sialic acid-linked influenza virus receptors in beagle
      dogs.
AB  - Reports of influenza A virus infections in dogs has received considerable
      attention from veterinarians, virologists, and epidemiologists. Interaction
      between influenza viral hemagglutinin and cell oligosaccharides containing sialic
      acid residues results in infection. Sialic acids have an alpha-2,3-linkage to the
      penultimate galactose in the avian influenza virus receptor and an alpha-2,6
      linkage in the human receptor. To date, there are no detailed data on the tissue
      distribution or histological features of either type of sialic acid-linked
      influenza virus receptors in beagle dogs, which are common laboratory animals and
      pets. We conducted the current study to visualize the in situ tissue distribution
      of both sialic acid-linked influenza virus receptors in various organs of beagle
      dogs using Maackia amurensis lectin II and Sambucus nigra agglutinin. Both alpha
      2,3- and alpha-2,6-sialic acid-linked receptors were detected in the endothelial
      cells of the respiratory tract and other organs. Endothelial cells of most
      gastrointestinal organs were negative for alpha-2,3-sialic acid-linked receptors
      in the dogs. Our results suggested that these canine organs may be affected by
      influenza virus infection. The findings from our study will also help evaluate
      the occurrence and development of influenza virus infections in dogs.

PMID- 23000578
TI  - Evidence for estrogen receptor expression during medullary bone formation and
      resorption in estrogen-treated male Japanese quails (Coturnix coturnix japonica).
AB  - The temporal expression of estrogen receptor (ER)-alpha and ER-beta mRNA was
      examined in male Japanese quails. Femurs of quails receiving 17beta-estradiol
      underwent RT-PCR and histochemical analysis 1 to 15 days after treatment.
      Untreated quails were used as controls (day 0). Between days 0 and 5, cells
      lining the bone endosteal surface differentiated into osteoblasts, which in turn
      formed medullary bone. Expression of ER-alpha was already observed on day 0 and
      increased slightly during bone formation whereas ER-beta was hardly detected
      throughout this process. After osteoclasts appeared on the medullary bone
      surface, this type of bone disappeared from the bone marrow cavity (days 7~15).
      ER-alpha expression simultaneously decreased slightly and ER-beta levels remained
      very low. These results suggest that estrogen activity mediated by ER-alpha not
      only affects medullary bone formation but also bone resorption.

PMID- 23000579
TI  - The effect of melanocortin (Mc3 and Mc4) antagonists on serotonin-induced food
      and water intake of broiler cockerels.
AB  - The current study was designed to examine the effects of intracerebroventricular
      injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and
      MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking
      responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment
      1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 ug
      serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being
      injected with 10 ug serotonin. For Experiment 3, the chickens were given 10 ug
      serotonin after receiving 2 nmol MCL0020, and the level of food and water intake
      was determined 3 h post-injection. Results of this study showed that serotonin
      decreased food intake but increased water intake among the FD24 broiler cockerels
      and that these effects occurred in a dose-dependent manner. The inhibitory effect
      of serotonin on food intake was significantly attenuated by pretreatment with
      SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake
      was not altered by this pretreatment. These results suggest that serotonin
      hypophagia and hyperdipsia were mediated by different mechanisms in the central
      nervous system, and that serotonin required downstream activation of McRs to
      promote hypophagia but not hyperdipsia in the FD24 chickens.

PMID- 23000580
TI  - Activation of Akt/protein kinase B mediates the protective effects of mechanical
      stretching against myocardial ischemia-reperfusion injury.
AB  - Akt/protein kinase B is a well-known cell survival factor and activated by many
      stimuli including mechanical stretching. Therefore, we evaluated the
      cardioprotective effect of a brief mechanical stretching of rat hearts and
      determined whether activation of Akt through phosphatidylinositol 3-kinase(PI3K)
      is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning
      reduced infarct size and improved postischemic cardiac function compared to the
      control group. Phosphorylation of Akt and its downstream substrate, GSK-3beta,
      was increased by mechanical stretching and completely blocked by wortmannin, a
      PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3beta inhibitors) before
      ischemia induction mimicked the protective effects of SIC on rat heart.
      Gadolinium (Gd3(+)), a blocker of stretch-activated ion channels (SACs),
      inhibited the stretch-induced phosphorylation of Akt and GSK-3beta. Furthermore,
      SIC was abrogated by wortmannin and Gd3(+). In vivo stretching induced by an
      aorto-caval shunt increased Akt phosphorylation and reduced myocardial
      infarction; these effects were diminished by wortmannin and Gd3(+) pretreatment.
      Our results showed that mechanical stretching can provide cardioprotection
      against ischemia-reperfusion injury. Additionally, the activation of Akt, which
      might be regulated by SACs and the PI3K pathway, plays an important role in SIC.

PMID- 23000581
TI  - Exendin-4 improves resistance to Listeria monocytogenes infection in diabetic
      db/db mice.
AB  - The incidence of diabetes mellitus is increasing among companion animals. This
      disease has similar characteristics in both humans and animals. Diabetes is
      frequently identified as an independent risk factor for infections associated
      with increased mortality. In the present study, homozygous diabetic (db/db) mice
      were infected with Listeria (L.) monocytogenes and then treated with the anti
      diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice,
      decreased CD11b(+) macrophage populations with higher lipid content and lower
      phagocytic activity were observed. Exendin-4 lowered high lipid levels and
      enhanced phagocytosis in macrophages from db/db mice infected with L.
      monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved
      ex vivo bacteria clearance by macrophages in the animals. Liver histology
      examined during L. monocytogenes infection indicated that abscess formation was
      much milder in exendin-4-treated db/db mice than in the control animals.
      Moreover, mechanistic studies demonstrated that expression of ATP binding
      cassette transporter 1, a sterol transporter, was higher in macrophages isolated
      from the exendin-4-treated db/db mice. Overall, our results suggest that exendin
      4 decreases the risk of infection in diabetic animals by modifying the
      interaction between intracellular lipids and phagocytic macrophages.

PMID- 23000582
TI  - Hsp70 and HSF-1 expression is altered in the tissues of pigs transported for
      various periods of times.
AB  - The aim of this study was to assess changes of Hsp70 and HSF-1 protein and mRNA
      expression in stress-sensitive organs of pigs during transportation for various
      periods of time. Twenty pigs were randomly divided into four groups (0 h, 1 h, 2
      h, and 4 h of transportation). A significant increased activity of AST and CK was
      observed after 1 h and 2 h of transportation. Histopathological changes in the
      heart, liver, and stomach indicated that these organs sustained different degrees
      of injury. Hsp70 protein expression in the heart and liver of transported pigs
      did not change significantly while it increased significantly (p < 0.05) in the
      stomach. Hsp70 mRNA levels decreased significantly (p < 0.05) in the heart after
      4 h of transportation. However, mRNA expression increased significantly in the
      liver after 1 (p < 0.05) and 4 h (p < 0.01) of transportation, and increased
      significantly in the stomach of the transported pigs after 1, 4 (p < 0.01), and 2
      h (p < 0.05). HSF-1 levels were reduced at 1 and 4 h (p < 0.05) only in the
      hearts of transported pigs. These results indicate that Hsp70 mediates distinct
      stress-related functions in different tissues during transportation.

PMID- 23000583
TI  - Pathogen translocation and histopathological lesions in an experimental model of
      Salmonella Dublin infection in calves receiving lactic acid bacteria and lactose
      supplements.
AB  - The purpose of this study was to evaluate the capacity of a lactic acid bacteria
      (LAB) inoculum to protect calves with or without lactose supplements against
      Salmonella Dublin infection by evaluating histopathological lesions and pathogen
      translocation. Fifteen calves were divided into three groups [control group (C
      G), a group inoculated with LAB (LAB-G), and a group inoculated with LAB and
      given lactose supplements (L-LAB-G)] with five, six, and four animals,
      respectively. The inoculum, composed of Lactobacillus (L.) casei DSPV 318T, L.
      salivarius DSPV 315T, and Pediococcus acidilactici DSPV 006T, was administered
      with milk replacer. The LAB-G and L-LAB-G received a daily dose of 10(9) CFU/kg
      body weight of each strain throughout the experiment. Lactose was provided to the
      L-LAB-G in doses of 100 g/day. Salmonella Dublin (2 * 10(10) CFU) was orally
      administered to all animals on day 11 of the experiment. The microscopic lesion
      index values in target organs were 83%, 70%, and 64.3% (p < 0.05) for the C-G,
      LAB-G, and L-LAB-G, respectively. Administration of the probiotic inoculum was
      not fully effective against infection caused by Salmonella. Although probiotic
      treatment was unable to delay the arrival of pathogen to target organs, it was
      evident that the inoculum altered the response of animals against pathogen
      infection.

PMID- 23000584
TI  - Prevalence of peste des petits ruminants among sheep and goats in India.
AB  - This study measured the clinical prevalence of peste des petits ruminants (PPR)
      among sheep and goats in India between 2003 and 2009 by analyzing clinical
      samples from suspected cases of PPR that were submitted to the Rinderpest and
      Allied Disease Laboratory, Division of Virology, IVRI, Mukteswar for PPR
      diagnosis. PPR outbreaks were confirmed by detecting PPR virus (PPRV)-specific
      antigen in the clinical samples. Clinical samples (blood, nasal swabs, spleen,
      lymph node, kidney, liver, intestine, and pooled tissue materials) were taken
      from a total of 592 sheep and 912 goats in different states of India and screened
      for the presence of PPRV antigen using a monoclonal antibody based sandwich ELISA
      kit. A total of 20, 38, and 11 laboratory-confirmed PPR outbreaks occurred among
      sheep, goat, and combined sheep and goat populations, respectively. Our findings
      provide evidence of widespread PPR endemicity in India. The underlying reasons
      could be variations in husbandry practices in different geographical regions,
      agro-climatic conditions, and livestock migration. Furthermore, decrease in the
      number of PPR outbreaks over time might be due to the effectiveness of current
      live PPR vaccines and timely vaccination of target species. Vaccination against
      PPR has been practiced in India since 2002 to control this disease.

PMID- 23000585
TI  - Protective effects of recombinant Brucella abortus Omp28 against infection with a
      virulent strain of Brucella abortus 544 in mice.
AB  - The outer membrane proteins (OMPs) of Brucella (B.) abortus have been extensively
      studied, but their immunogenicity and protective ability against B. abortus
      infection are still unclear. In the present study, B. abortus Omp28, a group 3
      antigen, was amplified by PCR and cloned into a maltose fusion protein expression
      system. Recombinant Omp28 (rOmp28) was expressed in Escherichia coli and was then
      purified. Immunogenicity of rOmp28 was confirmed by Western blot analysis with
      Brucella-positive mouse serum. Furthermore, humoral- or cell-mediated immune
      responses measured by the production of IgG1 or IgG2a in rOmp28-immunized mice
      and the ability of rOmp28 immunization to protect against B. abortus infection
      were evaluated in a mouse model. In the immunogenicity analysis, the mean titers
      of IgG1 and IgG2a produced by rOmp28-immunized mice were 20-fold higher than
      those of PBS-treated mice throughout the entire experimental period. Furthermore,
      spleen proliferation and bacterial burden in the spleen of rOmp28-immunized mice
      were approximately 1.5-fold lower than those of PBS-treated mice when challenged
      with virulent B. abortus. These findings suggest that rOmp28 from B. abortus is a
      good candidate for manufacturing an effective subunit vaccine against B. abortus
      infection in animals.

PMID- 23000586
TI  - The effect of seasonal variation on anthrax epidemiology in the upper Zambezi
      floodplain of western Zambia.
AB  - Anthrax has become endemic throughout the upper Zambezi floodplain located in the
      Western Province of Zambia over the recent years. To date, no comprehensive study
      has been carried out to determine whether recurrence of anthrax outbreaks may be
      linked to differences in precipitation and human activities. Retrospective data
      for the period 1999 to 2007 showed that a total of 1,216 bovine cases of anthrax
      were reported. During the same period, 1,790 human anthrax cases and a
      corresponding case fatality rate of 4.63% (83/1,790) was documented in the upper
      Zambezi floodplain. Occurrence of human cases was highly correlated with cattle
      outbreaks (r = 0.94, p < 0.001). Differences in precipitation were significantly
      associated with the occurrence of anthrax outbreaks (chi(2) = 4.75, p < 0.03),
      indicating that the likelihood of outbreaks occurring was higher during the dry
      months when human occupancy of the floodplain was greater compared to the
      flooding months when people and  livestock moved out of this region. Human
      dependency on the floodplain was shown to significantly influence the
      epidemiology of anthrax in the upper Zambezi floodplain of western Zambia.
      Methods for mitigating anthrax outbreaks by disrupting the cycle of transmission
      are herein highlighted.

PMID- 23000587
TI  - Comparing the osteogenic potential of canine mesenchymal stem cells derived from
      adipose tissues, bone marrow, umbilical cord blood, and Wharton's jelly for
      treating bone defects.
AB  - Alternative sources of mesenchymal stem cells (MSCs) for replacing bone marrow
      (BM) have been extensively investigated in the field of bone tissue engineering.
      The purpose of this study was to compare the osteogenic potential of canine MSCs
      derived from adipose tissue (AT), BM, umbilical cord blood (UCB), and Wharton's
      jelly (WJ) using in vitro culture techniques and in vivo orthotopic implantation
      assays. After canine MSCs were isolated from various tissues, the proliferation
      and osteogenic potential along with vascular endothelial growth factor (VEGF)
      production were measured and compared in vitro. For the in vivo assay, MSCs
      derived from each type of tissue were mixed with beta-tricalcium phosphate and
      implanted into segmental bone defects in dogs. Among the different types of MSCs,
      AT-MSCs had a higher proliferation potential and BM-MSCs produced the most VEGF.
      AT-MSCs and UCB-MSCs showed greater in vitro osteogenic potential compared to the
      other cells. Radiographic and histological analyses showed that all tested MSCs
      had similar osteogenic capacities, and the level of new bone formation was much
      higher with implants containing MSCs than cell-free implants. These results
      indicate that AT-MSCs, UCB-MSCs, and WJ-MSCs can potentially be used in place of
      BM-MSCs for clinical bone engineering procedures.

PMID- 23000588
TI  - Contrast-enhanced ultrasound analysis of renal perfusion in normal micropigs.
AB  - Contrast-enhanced ultrasound is one of method for evaluating renal perfusion. The
      purpose of this project was to assess perfusion patterns and dynamics in normal
      micropig kidney using ultrasonographic contrast media. Eight young healthy
      micropigs were included in this study. Micropigs were anesthetized with propofol
      and received an intravenous bolus of microbubble contrast media through an ear
      vein. Time/mean pixel value (MPV) curves were generated for selected regions in
      the right renal cortex and medulla. The parenchyma was enhanced in two phases.
      The cortex was first enhanced followed by a more gradual enhancement of the
      medulla. A significant difference in perfusion was detected between the cortex
      and medulla. Following the bolus injection, the average upslope was 0.68 +/- 0.27
      MPV/sec, downslope was -0.27 +/- 0.13 MPV/sec, baseline was 73.9 +/- 16.5 MPV,
      peak was 84.6 +/- 17.2 MPV, and time-to-peak (from injection) was 17.5 +/- 6.6
      sec for the cortex. For the medulla, the average upslope was 0.50 +/- 0.24
      MPV/sec, downslope was -0.12 +/- 0.06 MPV/sec, baseline was 52.7 +/- 7.0 MPV,
      peak was 65.2 +/- 9.3 MPV, and time-to-peak (from injection) was 27.5 +/- 5.0
      sec. These data can be used as normal reference values for studying young
      micropigs.

PMID- 23000589
TI  - Improved assessment of frozen/thawed mouse spermatozoa using fluorescence
      microscopy.
AB  - Genetically modified (GM) animals are unique mutants with an enormous scientific
      potential. Cryopreservation of pre-implantation embryos or spermatozoa is a
      common approach for protecting these lines from being lost or to store them in a
      repository. A mutant line can be taken out of a breeding nucleus only if
      sufficient numbers of samples with an appropriate level of quality are
      cryopreserved. The quality of different donors within the same mouse line might
      be heterogeneous and the cryopreservation procedure might also be error-prone.
      However, only limited amounts of material are available for analysis. To improve
      the monitoring of frozen/thawed spermatozoa, commonly used in vitro fertilization
      (IVF) followed by embryo transfer were replaced with animal-free techniques.
      Major factors for assessing spermatozoa quality (i.e., density, viability,
      motility, and morphology) were evaluated by fluorescence microscopy. For this, a
      live/dead cell staining protocol requiring only small amounts of material was
      created. Membrane integrity was then examined as major parameter closely
      correlated with successful IVF. These complex analyses allow us to monitor
      frozen/thawed spermatozoa from GM mice using a relatively simple staining
      procedure. This approach leads to a reduction of animal experiments and
      contributes to the 3R principles (replacement, reduction and refinement of animal
      experiments).

PMID- 23000590
TI  - Sample type is vital for diagnosing infection with peste des petits ruminants
      virus by reverse transcription PCR.
AB  - Peste des petits ruminants (PPR) diagnosis from suspected samples from sheep and
      goats was carried out. Buffy coat, tissues, and oculo-nasal swabs were analyzed
      using nucleoprotein (NP3/NP4) and fusion protein (F1/F2) gene primers,
      respectively. Analysis of the sample types and primer set revealed that buffy
      coat are the best type of samples for PPR diagnosis and the use of two set of
      primers will increase the number of positives.

PMID- 23000591
TI  - Use of canine small intestinal submucosa allograft for treating perineal hernias
      in two dogs.
AB  - Here, we describe two dogs in which canine small intestinal submucosa (SIS) was
      implanted as a biomaterial scaffold during perineal herniorrhaphy. Both dogs had
      developed severe muscle weakness, unilaterally herniated rectal protrusions, and
      heart problems with potential anesthetic risks. Areas affected by the perineal
      hernia (PH) located between the internal obturator and external anal sphincter
      muscles were reconstructed with naive canine SIS sheets. In 12 months, post
      operative complications such as wound infections, sciatic paralysis, rectal
      prolapse, or recurrence of the hernia were not observed. Symptoms of defecatory
      tenesmus also improved. Neither case showed any signs of rejection or specific
      immune responses as determined by complete and differential cell counts. Our
      findings demonstrate that canine SIS can be used as a biomaterial scaffold for PH
      repair in dogs.

PMID- 23000592
TI  - In-depth analysis of the secretome identifies three major independent secretory
      pathways in differentiating human myoblasts.
AB  - Efficient muscle regeneration requires cross talk between multiple cell types via
      secreted signaling molecules. However, as yet there has been no comprehensive
      analysis of this secreted signaling network in order to understand how it
      regulates myogenesis in humans. Using integrated proteomic and genomic
      strategies, we show that human muscle cells release not only soluble secreted
      proteins through conventional secretory mechanisms but also complex protein and
      nucleic acid cargos via membrane microvesicle shedding. The soluble secretome of
      muscle cells contains 253 conventionally secreted signaling proteins, including
      43 previously implicated in myogenesis, while others are known to modulate
      various cell types thus implying a much broader role for myoblasts in muscle
      remodeling. We also isolated and characterized two types of secreted membrane
      derived vesicles: nanovesicles harboring typical exosomal features and larger,
      morphologically distinct, microvesicles. While they share some common features,
      their distinct protein and RNA cargos suggest independent functions in
      myogenesis. We further demonstrate that both types of microvesicles can dock and
      fuse with adjacent muscle cells but also deliver functional protein cargo. Thus,
      the intercellular signaling networks invoked during muscle differentiation and
      regeneration may employ conventional soluble signaling molecules acting in
      concert with muscle derived microvesicles delivering their cargos directly into
      target cells.

PMID- 23000593
TI  - Discovery of serum proteomic biomarkers for prediction of response to infliximab
      (a monoclonal anti-TNF antibody) treatment in rheumatoid arthritis: an
      exploratory analysis.
AB  - Biologics such as TNF antagonists are a new class of drugs that have greatly
      improved Rheumatoid Arthritis (RA) treatment. However, for unknown reasons,
      individual patients with RA respond to one of these drugs but not to others even
      those targeting the same molecule. Methods to predict response are sorely needed
      because these drugs are currently selected by trial and error, what is very
      inefficient and prejudicial for the patient and the healthcare system. Here, we
      have explored the discovery of protein biomarkers in serum from patients treated
      with infliximab, one of the major anti-TNF drugs. The study was based in a
      quantitative proteomics approach using 8-plex iTRAQ labeling. It combined
      depletion of the most abundant serum proteins, two-dimensional LC fractionation,
      protein identification and relative quantification with a hybrid Orbitrap mass
      spectrometer. This approach allowed the identification of 315 proteins of which
      237 were confidently quantified with two or more peptides. The detection range
      covered up to 6 orders of magnitude including multiple proteins at the ng/mL
      level. A new set of putative biomarkers was identified comprising 14 proteins
      significantly more abundant in the non-responder patients. The differential
      proteins were enriched in apolipoproteins, components of the complement system
      and acute phase reactants. These results show the feasibility of this approach
      and provide a set of candidates for validation as biomarkers for the
      classification of RA patients before the beginning of treatment, so that
      anticipated non-responders could be treated with an alternative drug.

PMID- 23000594
TI  - A comprehensive proteomic analysis of Mycobacterium bovis bacillus Calmette
      Guerin using high resolution Fourier transform mass spectrometry.
AB  - Since 1921, Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been
      recognized as an important vaccine to prevent tuberculosis worldwide.
      Nonetheless, a global analysis of BCG proteome has not been clearly investigated.
      In this study, we performed an in-depth proteomic analysis of BCG under an in
      vitro cultivation condition using SDS-PAGE and high resolution Fourier transform
      mass spectrometry. In total, 3434 proteins (35,259 unique peptides) including 512
      transmembrane proteins were identified, covering ~87% of the predicted BCG
      proteome. Seven pseudogene protein products were also obtained and validated by
      RT-PCR at gene transcript level. Additionally, translational start sites of 832
      proteins were confirmed and 186 were extended using N-terminus-derived peptides.
      The physicochemical characteristics of all identified proteins were determined.
      Some predominant proteins, including PE and PPE family proteins, lipoproteins,
      heat shock proteins, transport proteins and low molecular weight protein
      antigens, are discussed, which represent potential prominent antigens in the
      humoral and cellular immune response. This study represents the most
      comprehensive BCG proteome to date, which will likely facilitate the design of
      vaccination and immunodiagnostic strategies against TB.

PMID- 23000595
TI  - Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase
      activity in mouse ovarian antral follicles in vitro.
AB  - Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries
      against various species of insects that attack crops and domestic animals. MXC
      reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC
      also induces atresia of antral follicles after 96 h in vitro. The current work
      tested the hypothesis that MXC induces morphological atresia at early time points
      (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity)
      and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results
      indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the
      ratio of Bax/Bcl2. At 48-96 h, MXC induced morphological atresia. At 24-96 h, MXC
      increased caspase activities. These data suggest that MXC may induce atresia by
      altering Bcl2 factors and inducing caspase activities in antral follicles.

PMID- 23000597
TI  - Challenges to the design, execution, and analysis of randomized controlled trials
      for inflammatory bowel disease.
AB  - Treatment of inflammatory bowel disease has greatly improved with the development
      of targeted, monoclonal antibody-based therapies. Tumor necrosis factor
      antagonists are frequently used to treat patients with Crohn's disease or
      ulcerative colitis, but they have side effects and their efficacy often decreases
      with use. New, more effective drugs are therefore needed and in development.
      However, many agents that appeared to be promising in preclinical studies have
      failed to show efficacy in clinical trials. We discuss possible reasons for the
      failures of these reagents in trials, which include the high rate of response to
      placebo, an inadequate range of doses, inappropriate timing of end point
      measurements, the changing therapeutic environment, and the competitive trial
      system. We also review regulatory guidelines for end points and trial design and
      recommend ways to improve trials.

PMID- 23000598
TI  - Development of robust hepatitis C virus genotype 4 subgenomic replicons.
AB  - Despite the prevalence of hepatitis C virus genotype 4, no replicon system is
      available for study of the genotype. To facilitate discovery and development of
      reagents against this virus, we synthesized and transcribed a genotype 4a
      subgenomic replicon and transfected Huh7-Lunet cells with it, which yielded very
      few colonies. However, when we used a new Huh-7-derived cell line, colony
      formation increased ~70-fold. We identified multiple adaptive mutations in the
      virus's nonstructural 3 or 4A proteins that allowed the cells to maintain stable,
      genotype 4a luciferase-encoding replicons. Several classes of hepatitis C virus
      inhibitors had different antiviral effects on genotypes 4a vs 1b. The genotype 4a
      replicon system we created will aid in the development of treatment regimens for
      all genotypes of hepatitis C virus.

PMID- 23000600
TI  - Baseline and 6-Week follow-up levels of PAF and activity of its metabolic enzymes
      in patients with heart failure and healthy volunteers--a pilot study.
AB  - This study aimed at evaluating the changes in platelet-activating factor (PAF)
      and its metabolic enzymes over a 6-week follow-up period in patients with newly
      diagnosed heart failure ([HF] n = 12) compared with age-, sex-, and BMI-matched
      apparently healthy volunteers (n = 10). The PAF, its key biosynthetic enzymes
      (lyso-PAF acetyltransferase [lyso-PAF-AT] and dithiothreitol [DTT]-insensitive
      CDP choline: 1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase [PAF-CPT]),
      and its catabolic isoenzymes (PAF-acetylhydrolase [PAF-AH] and lipoprotein
      associated phospholipase A2 [Lp-PLA2]) were measured in serum and leukocytes of
      participants. At baseline, patients with HF had lower median activities of lyso
      PAF-AT (P < .001) and PAF-CPT (P = .07) in parallel with PAF levels (P = .05) and
      higher activities of PAF-AH (P = .02) and Lp-PLA2 (P < .001) than controls. At
      follow-up, PAF-CPT and PAF levels marginally increased (P = .1), lyso-PAF-AT (P <
      .001) remained downregulated, while PAF-AH (P = .004) and Lp-PLA2 (P < .001)
      remained elevated compared with the controls. Newly diagnosed patients with HF
      under drug treatment have an affected profile of PAF biosynthetic enzymes and
      especially lyso-PAF-AT. 

PMID- 23000601
TI  - Association of serum gamma-glutamyltransferase with arterial stiffness in
      established coronary artery disease.
AB  - Serum gamma-glutamyltransferase (GGT) has been reported to predict vascular risk.
      We enrolled 978 patients (507 men and 471 women) with established coronary artery
      disease (CAD). The GGT, brachial-ankle pulse wave velocity ([baPWV] to assess
      arterial stiffness), and conventional risk factors were evaluated. The means of
      baPWV tend to increase in both genders according to GGT tertiles. Body mass
      index, GGT, logarithmical (systolic blood pressure [LnSBP]), uric acid (UA),
      total bilirubin, Ln (cholinesterase), and Ln (total cholesterol) were correlated
      with baPWV in men in a multivariate model. However, only GGT, LnSBP, UA, and Ln
      (high-density lipoprotein cholesterol) were correlated with baPWV in women. The
      GGT was a significant determinant for increased baPWV both in men (beta = 0.017;
      P < .001) and in women (beta = 0.015; P < .001). In conclusion, GGT was
      independently associated with increased arterial stiffness both in men and in
      women with established CAD.

PMID- 23000604
TI  - 8th Symposium on the role of the vestibular organs in space exploration.
      Introduction.

PMID- 23000603
TI  - Gold nanoparticle aggregation for quantification of oligonucleotides:
      optimization and increased dynamic range.
AB  - A variety of assays have been proposed to detect small quantities of nucleic
      acids at the point of care. One approach relies on target-induced aggregation of
      gold nanoparticles functionalized with oligonucleotide sequences complementary to
      adjacent regions on the targeted sequence. In the presence of the target
      sequence, the gold nanoparticles aggregate, producing an easily detectable shift
      in the optical scattering properties of the solution. The major limitations of
      this assay are that it requires heating and that long incubation times are needed
      to produce a result. This study aimed to optimize the assay conditions and
      optical readout, with the goals of eliminating the need for heating and reducing
      the time to result without sacrificing sensitivity or dynamic range. By
      optimizing assay conditions and measuring the spectrum of scattered light at the
      end point of incubation, we found that the assay is capable of producing
      quantifiable results at room temperature in 30min with a linear dynamic range
      spanning 150amol to 15fmol of target. If changes in light scattering are measured
      dynamically during the incubation process, the linear range can be expanded 2
      fold, spanning 50amol to 500fmol, while decreasing the time to result to 10min.

PMID- 23000599
TI  - Epigenetics of colorectal cancer.
AB  - In the early years of the molecular biology revolution, cancer research was
      mainly focused on genetic changes (ie, those that altered DNA sequences).
      Although this has been extremely useful as our understanding of the pathogenesis
      and biology of cancer has grown and matured, there is another realm in tumor
      development that does not involve changing the sequence of cellular DNA. This
      field is called "epigenetics" and broadly encompasses changes in the methylation
      of cytosines in DNA, changes in histone and chromatin structure, and alterations
      in the expression of microRNAs, which control the stability of many messenger
      RNAs and serve as "master regulators" of gene expression. This review focuses on
      the epigenetics of colorectal cancer and illustrates the impact epigenetics has
      had on this field.

PMID- 23000602
TI  - Enzymatic amplification of DNA/RNA hybrid molecular beacon signaling in nucleic
      acid detection.
AB  - A rapid assay operable under isothermal or nonisothermal conditions is described,
      where the sensitivity of a typical molecular beacon (MB) system is improved by
      using thermostable RNase H to enzymatically cleave an MB composed of a DNA stem
      and an RNA loop (R/D-MB). On hybridization of the R/D-MB to target DNA, there was
      a modest increase in fluorescence intensity (~5.7* above background) due to an
      opening of the probe and a concomitant reduction in the Forster resonance energy
      transfer efficiency. The addition of thermostable RNase H resulted in the
      cleavage of the RNA loop, which eliminated energy transfer. The cleavage step
      also released bound target DNA, enabling it to bind to another R/D-MB probe and
      rendering the approach a cyclic amplification scheme. Full processing of R/D-MBs
      maximized the fluorescence signal to the fullest extent possible (12.9* above
      background), resulting in an approximately 2- to 2.8-fold increase in the signal
      to-noise ratio observed isothermally at 50  degrees C following the addition of
      RNase H. The probe was also used to monitor real-time polymerase chain reactions
      by measuring enhancement of donor fluorescence on R/D-MB binding to amplified
      pUC19 template dilutions. Hence, the R/D-MB-RNase H scheme can be applied to a
      broad range of nucleic acid amplification methods.

PMID- 23000606
TI  - Experimental measurement of utricle dynamic response.
AB  - The utricle of the red-eared turtle was subjected to forced sinusoidal
      oscillations across various frequencies (10-125 Hz) and amplitudes (5-9 MUm) to
      determine dynamic characteristics of the utricle under natural inertial
      stimulation. The utricle was maintained in physiologic solution during the entire
      experiment. Utricular specimens were prepared so that the Otoconial Layer (OL)
      crystals were exposed yet undisturbed, and the neuroepithelium was secured to a
      glass slide with dental floss strands. A piezoelectric-actuated platform, fitted
      to the stage of the microscope, created controlled sinusoidal displacement along
      the utricle's medial-lateral direction. The OL surface displacement was measured
      through the microscope with high-speed video at 1500 fps. A sub-pixel image
      registration algorithm was used to achieve displacement resolution ? 15 nm. The
      Membranous Shelf (MS), that overlies the macula, was recorded with high-speed
      video under identical amplitude and frequency inputs and was used as a reference
      point. Maximum displacement amplitudes of the OL and MS were used to determine
      the Amplitude Ratio (AR) of the OL relative to the MS. ARs at various frequencies
      were fit to a single degree of freedom model of the utricle to determine the
      utricle's natural frequency of 363 Hz (95% confidence intervals: 328, 397) with a
      damping ratio of 0.96 (0.8, 1.12).

PMID- 23000607
TI  - Relationships between observer and Kalman Filter models for human dynamic spatial
      orientation.
AB  - How does the central nervous system (CNS) combine sensory information from
      semicircular canal, otolith, and visual systems into perceptions of rotation,
      translation and tilt? Over the past four decades, a variety of input-output
      ("black box") mathematical models have been proposed to predict human dynamic
      spatial orientation perception and eye movements. The models have proved useful
      in vestibular diagnosis, aircraft accident investigation, and flight simulator
      design. Experimental refinement continues. This paper briefly reviews the history
      of two widely known model families, the linear "Kalman Filter" and the nonlinear
      "Observer". Recent physiologic data supports the internal model assumptions
      common to both. We derive simple 1-D and 3-D examples of each model for
      vestibular inputs, and show why - despite apparently different structure and
      assumptions - the linearized model predictions are dynamically equivalent when
      the four free model parameters are adjusted to fit the same empirical data, and
      perceived head orientation remains near upright. We argue that the motion
      disturbance and sensor noise spectra employed in the Kalman Filter formulation
      may reflect normal movements in daily life and perceptual thresholds, and thus
      justify the interpretation that the CNS cue blending scheme may well minimize
      least squares angular velocity perceptual errors.

PMID- 23000608
TI  - Sensory conflict compared in microgravity, artificial gravity, motion sickness,
      and vestibular disorders.
AB  - Perceptual disturbances and motion sickness are often attributed to sensory
      conflict. We investigated several conditions: head movements in microgravity,
      periodic motions in 1-g, and locomotion with vestibular disorders. In every case,
      linear vectors such as linear and gravitational acceleration are crucial factors,
      as previously found for head movements in artificial gravity, and thus the
      importance of measuring linear vectors emerges as a common theme. By modeling the
      sensory conflict between the vestibular and somatosensory systems, we computed a
      measure of linear conflict known as the "Stretch Factor". We hypothesized that
      the motions with the greatest Stretch Factor would be the most provocative
      motions. RESULTS: For head movements in microgravity, the Stretch Factor can
      explain why fast movements are more provocative than slow movements, and why
      pitch movements are more provocative than yaw movements. For off-vertical-axis
      rotation (OVAR) in 1-g, the Stretch Factor predicts that the most provocative
      frequency is higher than that for vertical linear oscillation (VLO). For example,
      the same sensor dynamics can predict a most provocative frequency around 0.2 Hz
      for VLO but 0.3 Hz for OVAR, solving a mystery of this experimentally observed
      discrepancy. Finally, we determined that certain sensory conflict perceptions
      reported by vestibular patients could be explained via mathematical simulation.

PMID- 23000610
TI  - Influence of head orientation and viewpoint oscillation on linear vection.
AB  - Sensory conflict theories predict that adding simulated viewpoint oscillation to
      self-motion displays should generate significant and sustained visual-vestibular
      conflict and reduce the likelihood of illusory self-motion (vection). However,
      research shows that viewpoint oscillation enhances vection in upright observers.
      This study examined whether the oscillation advantage for vection depends on head
      orientation with respect to gravity. Displays that simulated forward/backward
      self-motion with/without horizontal and vertical viewpoint oscillation were
      presented to observers in upright (seated and standing) and lying (supine, prone,
      and left side down) body postures. Viewpoint oscillation was found to enhance
      vection for all of the body postures tested. Vection also tended to be stronger
      in upright postures than in lying postures. Changing the orientation of the head
      with respect to gravity was expected to alter the degree/saliency of the sensory
      conflict, which may explain the overall posture-based differences in vection
      strength. However, this does not explain why the oscillation advantage for
      vection persisted for all postures. Thus, the current postural and oscillation
      based vection findings appear to be better explained by ecology: Upright postures
      and oscillating flow (that are the norm during self-motion) improved vection,
      whereas lying postures and smooth optic flows (which are less common) impaired
      vection.

PMID- 23000609
TI  - Tests of walking balance for screening vestibular disorders.
AB  - Few reliable tests are available for screening people rapidly for vestibular
      disorders although such tests would be useful for a variety of testing
      situations. Balance testing is widely performed but of unknown value for
      screening. The goal of this study was to determine the value of tests of walking
      balance for screening people with vestibular impairments. We tested three groups
      of patients with known vestibular impairments: benign paroxysmal positional
      vertigo, unilateral vestibular weakness, and post-acoustic neuroma resection. We
      compared them to normal subjects. All subjects were independently ambulatory
      without gait aids. Subjects were tested on tandem walking (TW) with eyes open and
      eyes closed for 10 steps, walking with no additional head motions and with
      augmented head rotations in yaw for 7 m (WwHT), and an obstacle avoidance task,
      the Functional Mobility Test (FMT). Subjects wore a 3-D motion sensor centered at
      mid-torso to capture kinematic measures. Patients and normals differed
      significantly on some behavioral measures, such as the number of steps to perform
      TW, and on some but not all kinematic measures. ROC analyses, however, were at
      best only moderate, and failed to find strong differences and cut-points that
      would differentiate the groups. These findings suggest that although patients and
      normals differ in performance of these tests in some interesting ways the groups
      are not sufficiently different on these tests for easy use as screening tests to
      differentiate the populations.

PMID- 23000611
TI  - Are evolutionary hypotheses for motion sickness "just-so" stories?
AB  - Vertebrates have evolved rapidly conditionable nausea and vomiting reflexes
      mediated by gut and brainstem receptors, clearly as a defense against neurotoxin
      ingestion. In 1977 Treisman proposed that sensory orientation linkages to emetic
      centers evolved for the same reason, and that motion sickness was an accidental
      byproduct. It was an "adaptationist" explanation for motion sickness, since it
      assumed that evolution has shaped all phenotypic traits for survival advantage.
      Treisman's "poison" theory is plausible, and frequently cited as the accepted
      scientific explanation for motion sickness. However, alternative explanations
      have been proposed. The creation of hypotheses is an essential part of science -
      provided they are testable. This paper reviews the evidence for the Poison theory
      and several other adaptationist explanations. These hypotheses are certainly not
      "just-so stories", but supporting evidence is equivocal, and contradictory
      evidence exists Parsimony suggests an alternative "pluralistic" view: The
      vertebrate reticular formation maintains oxygenated blood flow to the brain,
      discriminates unexpected sensory stimuli- including postural disturbances, and
      detects and expels ingested neurotoxins. The three systems share
      neuroarchitectural elements but normally function independently. Brainstem
      sensory conflict neurons normally discriminate brief postural disturbances, but
      can be abnormally stimulated during prolonged passive transport (e.g. by boat,
      beginning about 150-200 generations ago). Sensory conflict signals cross couple
      into the neurotoxin expulsion and avoidance system, producing an arguably
      maladaptive emetic phenotype.

PMID- 23000612
TI  - Postural performance of vestibular loss patients under increased postural threat.
AB  - The effects of increasing postural task difficulty on balance control was
      investigated in 9 compensated vestibular loss patients whose results were
      compared to 11 healthy adults. Subjects were tested in static (stable support)
      and dynamic (sinusoidal translation of the support) conditions, both at floor
      level and at height (62 cm above the floor), and with and without vision, to
      create an additional postural threat. Wavelet analysis of the center of foot
      pressure displacement and motion analysis of the body segments were used to
      evaluate the postural performance. Evaluation questionnaires were used to examine
      the compensation level of the patients (DHI test), their general anxiety level
      (SAST), fear of height (subjective scale), and workload (NASA TLX test).
      (Vestibular loss patients rely more on vision and spend more energy maintaining
      balance than controls, but they use the same postural strategy as normals in both
      static and dynamic conditions.) Questionnaire data all showed differences in
      behavior and perceptions between the controls and the patients. However, at
      height and without vision, a whole body strategy leading to rigid posture
      replaces the head stabilization strategy found for standing at floor level. The
      effects of height on postural control can be attributable to an increase in
      postural threat and attention changes resulting from modifications in perception.

PMID- 23000613
TI  - Pre-flight sensorimotor adaptation protocols for suborbital flight.
AB  - Commercial suborbital flights, which include 3-5 minutes of 0 g between hyper-g
      launch and landing phases, will present suborbital passengers with a challenging
      sensorimotor experience. Based on the results of neurovestibular research in
      parabolic and orbital flight, and the anticipated wide range of fitness and
      experience levels of suborbital passengers, neurovestibular disturbances are
      likely to be problematic in this environment. Pre-flight adaptation protocols
      might alleviate some of these issues. Therefore, we describe a set of
      sensorimotor tests to evaluate passengers before suborbital flight, including
      assessment of the angular vestibulo-ocular reflex (VOR), ocular skew and
      disconjugate torsion, subjective visual vertical, and roll vection. Performance
      on these tests can be examined for correlations with in-flight experience, such
      as motion sickness, disorientation, and visual disturbances, based on
      questionnaires and cabin video recordings. Through an understanding of
      sensorimotor adaptation to parabolic and orbital flight, obtained from many
      previous studies, we can then suggest appropriate pre-flight adaptation
      procedures.

PMID- 23000614
TI  - Dynamic visual acuity testing for screening patients with vestibular impairments.
AB  - Dynamic visual acuity (DVA) may be a useful indicator of the function of the
      vestibulo-ocular reflex (VOR) but most DVA tests involve active head motion in
      the yaw plane. During gait the passive, vertical VOR may be more relevant and
      passive testing would be less likely to elicit compensatory strategies. The goal
      of this study was to determine if testing dynamic visual acuity during passive
      vertical motion of the subject would differentiate normal subjects from patients
      with known vestibular disorders. Subjects, normals and patients who had been
      diagnosed with either unilateral vestibular weaknesses or were post-acoustic
      neuroma resections, sat in a chair that could oscillate vertically with the head
      either free or constrained with a cervical orthosis. They viewed a computer
      screen 2 m away that showed Landholt C optotypes in one of 8 spatial
      configurations and which ranged in size from 0.4 to 1.0 logMAR. They were tested
      while the chair was stationary and while it was moving. Scores were worse for
      both groups during the dynamic condition compared to the static condition. In the
      dynamic condition patients' scores were significantly worse than normals' scores.
      Younger and older age groups differed slightly but significantly; the sample size
      was too small to examine age differences by decade. The data suggest that many
      well-compensated patients have dynamic visual acuity that is as good as age
      matched normals. Results of ROC analyses were only moderate, indicating that the
      differences between patients and normals were not strong enough, under the
      conditions tested, for this test to be useful for screening people to determine
      if they have vestibular disorders. Modifications of the test paradigm may make it
      more useful for screening potential patients.

PMID- 23000615
TI  - Vestibular-somatosensory convergence in head movement control during locomotion
      after long-duration space flight.
AB  - Space flight causes astronauts to be exposed to adaptation in both the vestibular
      and body load-sensing somatosensory systems. The goal of these studies was to
      examine the contributions of vestibular and body load-sensing somatosensory
      influences on vestibular mediated head movement control during locomotion after
      long-duration space flight. Subjects walked on a motor driven treadmill while
      performing a gaze stabilization task. Data were collected from three independent
      subject groups that included bilateral labyrinthine deficient (LD) patients,
      normal subjects before and after 30 minutes of 40% bodyweight unloaded treadmill
      walking, and astronauts before and after long-duration space flight. Motion data
      from the head and trunk segments were used to calculate the amplitude of angular
      head pitch and trunk vertical translation movement while subjects performed a
      gaze stabilization task, to estimate the contributions of vestibular reflexive
      mechanisms in head pitch movements. Exposure to unloaded locomotion caused a
      significant increase in head pitch movements in normal subjects, whereas the head
      pitch movements of LD patients were significantly decreased. This is the first
      evidence of adaptation of vestibular mediated head movement responses to unloaded
      treadmill walking. Astronaut subjects showed a heterogeneous response of both
      increases and decreases in the amplitude of head pitch movement. We infer that
      body load-sensing somatosensory input centrally modulates vestibular input and
      can adaptively modify vestibularly mediated head-movement control during
      locomotion. Thus, space flight may cause central adaptation of the converging
      vestibular and body load-sensing somatosensory systems leading to alterations in
      head movement control.

PMID- 23000616
TI  - Audit of hospital doctor training in sick note certification.
AB  - BACKGROUND: Sick note certification plays an important role in helping
      individuals access financial support and to return to work. Currently, hospital
      doctors receive very little training in sick note certification. AIMS: To
      evaluate the level of training received by hospital doctors and identify training
      needs. METHODS: A questionnaire was designed and distributed to doctors who were
      training at Plymouth Hospitals National Health Service Trust in July and November
      2011. After the first round audit an e-learning module was designed and locally
      advertised. The questionnaire was redistributed to assess the impact of the e
      learning module. RESULTS: In the first round, 64% of junior doctors reported no
      sick note certification training. Only 40% felt confident in writing sick note
      certificates, and 54% could not identify which certificates are commonly
      completed in the hospital environment. Hospital doctors who had completed the e
      learning module were better at identifying which certificates are appropriate to
      use in the hospital environment: Statement of fitness of work/Fit note (78%), Med
      10 (78%) and DS1500 (67%). The e-learning module also increased the confidence of
      hospital doctors in writing sick note certificates, assessing fitness for work,
      recommending work modifications and ability to direct patients to alternative
      forms of information. CONCLUSIONS: This is the first study to try and tackle the
      problem of poor knowledge of sick note certification among hospital doctors. The
      study demonstrates that an e-learning module is a simple but effective way of
      meeting the current training deficit.

PMID- 23000617
TI  - Gender-specific perturbations in modulatory inputs to motoneurons in a mouse
      model of amyotrophic lateral sclerosis.
AB  - The fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) is
      characterised by loss of motoneurons of the brainstem and spinal cord, and
      corticospinal neurons of the motor cortex. There is also increasing evidence of
      involvement of glial cells and interneurons, with non-cell autonomous disease
      mechanisms now thought to contribute to motoneuron degeneration in ALS. Given the
      apparent involvement of altered motoneuron excitability in ALS and the recent
      demonstration that motoneuron excitability is controlled by C-boutons, a specific
      class of synaptic input recently shown to originate from a small cluster of
      spinal interneurons, we hypothesised that perturbations in C-bouton inputs to
      motoneurons may contribute to altered excitability and the eventual degeneration
      of motoneurons in ALS. To begin to assess this we performed a detailed,
      developmental study of the anatomy of C-boutons in a mouse model of ALS (G93A
      SOD1 mutant). We found that C-bouton number is unchanged in ALS mice compared to
      wildtype littermates at any age. In contrast, we found that the size of C-boutons
      increases in ALS mice between postnatal day (P)8 and P30, with boutons remaining
      larger throughout symptomatic stages (P120-P140). Interestingly, we found that C
      boutons are only enlarged in male mice. We found no evidence of concomitant
      changes in clusters of postsynaptic proteins known to align with C-boutons (Kv2.1
      K(+) channels and m(2)-type muscarinic receptors). In conclusion, these data
      support the involvement of pre-symptomatic changes in C-bouton anatomy in ALS
      pathogenesis and in particular mechanisms underlying the male bias of this
      disease.

PMID- 23000618
TI  - Possible involvement of type 1 inositol 1,4,5-trisphosphate receptors up
      regulated by dopamine D1 and D2 receptors in mouse nucleus accumbens neurons in
      the development of methamphetamine-induced place preference.
AB  - Little is known about regulatory mechanisms of type 1 inositol-1,4,5-triphosphate
      receptor (IP(3)R-1) expression in conditioned place preference by methamphetamine
      (METH), though significant enhancement of IP(3)R-1 expression in the mouse
      frontal cortex and limbic forebrain by intermittent administration of cocaine is
      reported. The present study investigated the role and regulation of IP(3)R-1 in
      mice with METH-induced place preference. Injection of IP(3)R antagonists with
      different chemical structures, 2-aminophenoxyethane-borate and xestospongin C,
      into the mouse nucleus accumbens (NAcc) dose-dependently inhibited METH-induced
      place preference. The levels of IP(3)R-1 protein in the NAcc of METH-conditioned
      mice significantly increased, which was completely abolished by microinjection of
      SCH23390 and raclopride, selective dopamine D1-like and D2-like receptor (D1 and
      D2DR) antagonists respectively, into the mouse NAcc. Immunohistochemical
      assessment revealed co-localization of immunoreactivity for IP(3)R-1 and those
      for D1 and D2DRs in the NAcc. These findings suggest that IP(3)R-1 could be
      involved in the development of METH-induced place preference and that D1 and
      D2DRs in the NAcc of mice showing METH-induced place preference play possible
      regulatory roles in IP(3)R-1 expression.

PMID- 23000619
TI  - Progesterone down-regulates spinal cord inflammatory mediators and increases
      myelination in experimental autoimmune encephalomyelitis.
AB  - In mice with experimental autoimmune encephalomyelitis (EAE) pretreatment with
      progesterone improves clinical signs and decreases the loss of myelin basic
      protein (MBP) and proteolipid protein (PLP) measured by immunohistochemistry and
      in situ hybridization. Presently, we analyzed if progesterone effects in the
      spinal cord of EAE mice involved the decreased transcription of local
      inflammatory mediators and the increased transcription of myelin proteins and
      myelin transcription factors. C57Bl/6 female mice were divided into controls, EAE
      and EAE receiving progesterone (100mg implant) 7 days before EAE induction.
      Tissues were collected on day 17 post-immunization. Real time PCR technology
      demonstrated that progesterone blocked the EAE-induced increase of the
      proinflammatory mediators tumor necrosis factor alpha (TNFalpha) and its receptor
      TNFR1, the microglial marker CD11b and toll-like receptor 4 (TLR4) mRNAs, and
      increased mRNA expression of PLP and MBP, the myelin transcription factors NKx2.2
      and Olig1 and enhanced CC1+oligodendrocyte density respect of untreated EAE mice.
      Immunocytochemistry demonstrated decreased Iba1+microglial cells. Confocal
      microscopy demonstrated that TNFalpha colocalized with glial-fibrillary acidic
      protein+astrocytes and OX-42+microglial cells. Therefore, progesterone treatment
      improved the clinical signs of EAE, decreased inflammatory glial reactivity and
      increased myelination. Data suggest that progesterone neuroprotection involves
      the modulation of transcriptional events in the spinal cord of EAE mice.

PMID- 23000620
TI  - Hypoxia-induced hypothermia mediated by the glutamatergic transmission in the
      lateral preoptic area.
AB  - Hypoxia evokes a regulated decrease in the body core temperature, which response
      is mediated, at least in part, by noradrenaline (NA) and nitric oxide (NO) in the
      rostromedial preoptic area (POA) of the hypothalamus. In the accompanying paper,
      it was shown that glutamatergic activation of the lateral POA also evokes
      hypothermic responses. Here, I tested the hypothesis that the glutamatergic
      transmission in the lateral POA is critically involved in the neural mechanism of
      hypoxia-induced hypothermia. Hypoxic ventilation (10% O(2)-90% N(2), 5 min) as
      well as a single microinjection of NA (50 pmol) or the NO donor sodium
      nitroprusside (8.4 nmol) into the rostromedial POA evoked an increase in the tail
      skin temperature and a decrease in the colonic temperature in urethane-chloralose
      anesthetized, neuromuscularly blocked, artificially ventilated rats. All of these
      responses were greatly attenuated by pretreatment with multiple microinjections
      of kynurenic acid (10 nmol, four locations), a nonselective glutamate receptor
      antagonist, but not by those with saline solution, in the bilateral rostral and
      central parts of the lateral POA. These results suggest that the NA- and NO
      sensitive structure in the rostromedial POA activated the glutamatergic
      transmission in the lateral POA to mediate hypoxia-induced hypothermia.

PMID- 23000621
TI  - The distribution of phosphodiesterase 2A in the rat brain.
AB  - The phosphodiesterases (PDEs) are a superfamily of enzymes that regulate spatio
      temporal signaling by the intracellular second messengers cAMP and cGMP. PDE2A is
      expressed at high levels in the mammalian brain. To advance our understanding of
      the role of this enzyme in regulation of neuronal signaling, we here describe the
      distribution of PDE2A in the rat brain. PDE2A mRNA was prominently expressed in
      glutamatergic pyramidal cells in cortex, and in pyramidal and dentate granule
      cells in the hippocampus. Protein concentrated in the axons and nerve terminals
      of these neurons; staining was markedly weaker in the cell bodies and proximal
      dendrites. In addition, in both hippocampus and cortex, small populations of non
      pyramidal cells, presumed to be interneurons, were strongly immunoreactive. PDE2A
      mRNA was expressed in medium spiny neurons in neostriatum. Little
      immunoreactivity was observed in cell bodies, whereas dense immunoreactivity was
      found in the axon tracts of these neurons and their terminal regions in globus
      pallidus and substantia nigra pars reticulata. Immunostaining was dense in the
      medial habenula, but weak in other diencephalic regions. In midbrain and
      hindbrain, immunostaining was restricted to discrete regions of the neuropil or
      clusters of cell bodies. These results suggest that PDE2A may modulate cortical,
      hippocampal and striatal networks at several levels. Preferential distribution of
      PDE2A into axons and terminals of the principal neurons suggests roles in
      regulation of axonal excitability or transmitter release. The enzyme is also in
      forebrain interneurons, and in mid- and hindbrain neurons that may modulate
      forebrain networks and circuits.

PMID- 23000622
TI  - Dopamine receptor inactivation in the caudate-putamen differentially affects the
      behavior of preweanling and adult rats.
AB  - The irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ) has been used to study the ontogeny of dopamine (DA)
      receptor functioning in young and adult rats. Most notably, systemic
      administration of EEDQ blocks the DA agonist-induced behaviors of adult rats,
      while leaving the behavior of preweanling rats unaffected. The purpose of the
      present study was to: (a) determine whether the age-dependent actions of EEDQ
      involve receptors located in the dorsal caudate-putamen (CPu) and (b) confirm
      that EEDQ's behavioral effects result from the inactivation of DA receptors
      rather than some other receptor type. In Experiment 1, EEDQ or DMSO was
      bilaterally infused into the CPu on PD 17 or PD 84. After 24h, rats were given
      bilateral microinjections of the full DA agonist R(-)-propylnorapomorphine (NPA)
      or vehicle into the dorsal CPu and behavior was assessed for 40 min. In
      Experiment 2, preweanling rats were treated as just described, except that DA
      receptors were protected from EEDQ-induced alkylation by administering systemic
      injections of D1 (SCH23390) and D2 (sulpiride) receptor antagonists. As
      predicted, microinjecting EEDQ into the dorsal CPu attenuated the NPA-induced
      locomotor activity and stereotypy of adult rats. In contrast, rats given
      bilateral EEDQ infusions on PD 17 exhibited a potentiated locomotor response when
      treated with NPA. Experiment 2 showed that DA receptor inactivation was
      responsible for NPA's actions. A likely explanation for these results is that
      EEDQ inactivates a sizable percentage of DA receptors on PD 17, but leaves the
      remaining receptors in a supersensitive state. This receptor supersensitivity,
      which probably involves alterations in G protein coupling, could account for NPA
      induced locomotor potentiation. It is likely that adult rats to not show a
      similar EEDQ-induced change in receptor dynamics or DA receptor inactivation was
      more complete in older animals and effectively eliminated the expression of DA
      agonist-induced behaviors.

PMID- 23000624
TI  - Distribution maps of D-dopachrome tautomerase in the mouse brain.
AB  - D-Dopachrome tautomerase is an enzyme related by amino acid sequence and
      catalytic activity to macrophage migration inhibitory factor. Both of these small
      molecules are pro-inflammatory cytokines mediating broad innate immune responses.
      Although it is well established that the gene product of D-dopachrome tautomerase
      is widely expressed in liver and kidney cells, no study has mapped the
      distribution pattern of this tautomeric enzyme in the mammalian nervous system.
      Here, we address this void by characterizing the cellular localization of D
      dopachrome tautomerase in the adult mouse brain. Two well-characterized
      polyclonal antibodies were used for Western blotting and immunohistochemical
      localization of the endogenous tautomeric enzyme. Our results show that D
      dopachrome tautomerase is present throughout the brain parenchyma with a large
      fraction of heterogeneous interneurons harboring a stable and robust expression
      of the enzyme. These data point to a potential involvement of D-dopachrome
      tautomerase activity in the mature mouse brain, and suggest some functional and
      evolutionary relationship between innate immunity and tautomerization of D
      dopachrome in mammalian species.

PMID- 23000623
TI  - Cross-sensitization of histamine-independent itch in mouse primary sensory
      neurons.
AB  - Overexpression of pruritogens and their precursors may contribute to the
      sensitization of histamine-dependent and -independent itch-signaling pathways in
      chronic itch. We presently investigated self- and cross-sensitization of
      scratching behavior elicited by various pruritogens, and their effects on primary
      sensory neurons. The MrgprC11 agonist BAM8-22 exhibited self- and reciprocal
      cross-sensitization of scratching evoked by the protease-activated receptor-2
      (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross
      sensitized BAM8-22-evoked scratching. Histamine unidirectionally cross-sensitized
      scratching evoked by chloroquine and BAM8-22. SLIGRL unidirectionally cross
      sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells
      responded to various combinations of pruritogens and algogens. Neither
      chloroquine, BAM8-22 nor histamine had any effect on responses of DRG cell
      responses to subsequently applied pruritogens, implying that their behavioral
      self- and cross-sensitization effects are mediated indirectly. SLIGRL
      unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8-22,
      consistent with the behavioral data. These results indicate that unidirectional
      cross-sensitization of histamine-independent itch-signaling pathways might occur
      at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings
      is a potential target to reduce sensitization associated with chronic itch.

PMID- 23000625
TI  - Exendin-4 improved rat cortical neuron survival under oxygen/glucose deprivation
      through PKA pathway.
AB  - Previous studies demonstrated that exendin-4 (Ex-4) may possess neurotrophic and
      neuroprotective functions in ischemia insults, but its mechanism remained
      unknown. Here, by using real-time PCR and ELISA, we identified the distribution
      of active GLP-1Rs in the rat primary cortical neurons. After establishment of an
      in vitro ischemia model by oxygen/glucose deprivation (OGD), neurons were treated
      with various dosages of Ex-4. The MTT assay showed that the relative survival
      rate increased with the dosage of Ex-4 ranging from 0.2 to 0.8 MUg/ml (P<0.001,
      vs. OGD group). The apoptosis rate was reduced from (49.47+/-2.70)% to (14.61+/
      0.81)% after Ex-4 treatment (0.4 MUg/ml) 12h after OGD (P<0.001). Moreover,
      immunofluorescence staining indicated that Ex-4 increased glucose-regulated
      proteins 78 (GRP78) and reduced C/EBP-homologous protein (CHOP). Western blot
      analysis demonstrated that, after neurons were treated with Ex-4, GRP78 was up
      regulated over time (P<0.01, vs. OGD group), while CHOP levels rose to a peak 8h
      after OGD and then decreased (P<0.05, vs. OGD group). This effect was changed by
      both the protein kinase A (PKA) inhibitor H89 (P<0.01, P<0.05, respectively, vs.
      Ex-4 group) and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002
      (P<0.01, P<0.01, respectively, vs. Ex-4 group) but not by the mitogen-activated
      protein kinase (MAPK) inhibitor U0126. Our study also revealed that, compared
      with the Ex-4 group, inhibition of the PKA signaling pathway significantly
      decreased the survival rate of neurons, down-regulated the expression of B-cell
      lymphoma 2 (Bcl-2) and up-regulated the Bax expression 3h after ODG (P<0.05,
      P<0.01, respectively), while neither PI3K nor MAPK inhibition exerted such
      effects. Furthermore, Western blotting exhibited that PKA expression was elevated
      in the presence or absence of OGD insults (P<0.05). This study indicated that Ex
      4 protected neurons against OGD by modulating the unfolded protein response (UPR)
      through the PKA pathway and may serve as a novel therapeutic agent for stroke.

PMID- 23000627
TI  - Behavioural outcomes of perinatal maternal fluoxetine treatment.
AB  - During and following pregnancy, women are at considerable risk of experiencing
      depression. For treatment, selective serotonin reuptake inhibitor drugs, such as
      fluoxetine, are commonly prescribed, yet the potential effects of perinatal
      exposure to these drugs on the brain and behaviour have not been examined in
      humans beyond childhood. This is despite abundant evidence from studies using
      rodents indicating that altered serotonin levels early in life affect
      neurodevelopment and behavioural outcomes. These reported effects on behaviour
      are inconsistent, however, and the testing of females has often been overlooked.
      In the present study, the behavioural outcomes of female mice perinatally
      (embryonic day 15 to postnatal day 12) treated with fluoxetine (25mg/kg/day) via
      a non-stressful method of maternal administration were assessed using a battery
      of tests. Maternal treatment resulted in subtle alterations in anxiety-like and
      depression-like behaviour in early adulthood, with a decrease in both types of
      behaviour as well as body weight. Though altered anxiety and depression have
      previously been reported in this area of research, decreased anxiety is a novel
      finding. While there was little effect of perinatal maternal fluoxetine treatment
      on many of the behaviours assessed, the capacity to alter "emotional" behaviours
      in mice has implications with regard to research on human infant fluoxetine
      exposure.

PMID- 23000626
TI  - Distinct developmental principles underlie the formation of ipsilateral and
      contralateral whisker-related axonal patterns of layer 2/3 neurons in the barrel
      cortex.
AB  - Axonal organizations with specific patterns underlie the functioning of local
      intracortical circuitry, but their precise anatomy and development still remain
      elusive. Here, we selectively visualized layer 2/3 neurons using in utero
      electroporation and examined their axonal organization in the barrel cortex
      contralateral to the electroporated side. We found that callosal axons run
      preferentially in septal regions of layer 4 and showed a whisker-related pattern
      in the contralateral barrel cortex in rats and mice. In addition, presynaptic
      marker proteins were found in this whisker-related axonal organization. Although
      the whisker-related patterns were observed in both the ipsilateral and
      contralateral barrel cortex, we found a difference in their developmental
      processes. While the formation of the whisker-related pattern in the ipsilateral
      cortex consisted of two distinct steps, that in the contralateral cortex did not
      have the 1st step, in which the axons were diffusely distributed without
      preference to septal or barrel regions. We also found that these more diffuse
      axons ran close to radial glial fibers. Together, our results uncovered a whisker
      related axonal pattern of callosal axons and two independent developmental
      processes involved in the formation of the axonal trajectories of layer 2/3
      neurons.

PMID- 23000628
TI  - Cell proliferation pattern in adult zebrafish forebrain is sexually dimorphic.
AB  - Cell proliferation, differentiation and cell death are considered key players for
      brain plasticity mechanisms that underlie sex specific phenotypes in brain and
      behavior. Well-documented examples of sex-specific neurogenesis are the avian
      song system telencephalic areas and the mammalian hippocampus. The present study
      questioned whether sex difference in cell proliferation represents a conserved
      feature of adult brain plasticity, using the neurogenetic model organism
      zebrafish (Danio rerio). For this, active cycling progenitors were determined by
      means of 5'-bromo-2'-deoxyuridine (BrdU) immunohistochemistry, in adult male and
      female zebrafish forebrain proliferation zones. In addition, apoptotic figures
      were measured using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      nick-end labeling method. Short-term survival experiments showed that the medial
      zone of dorsal telencephalic area (Dm) the ventral part of periventricular
      pretectal nucleus (PPv) and the periventricular nucleus of posterior tuberculum,
      exhibited higher levels of cycling cells in females, while the dorsal zone of
      periventricular hypothalamus displayed higher density of mitotically active cells
      in males. Apoptotic figures were present in all major proliferation zones, but
      did not differ between sexes. However, apoptotic figures paralleled the density
      of dividing cells, suggesting a close relationship of cell birth and cell death.
      Interestingly, in long-term survival experiments, sex differences were preserved
      in the long-lasting BrdU cells within the telencephalic Dm (homologous to
      mammalian amygdala), and the diencephalic PPv, areas that have a role in
      emotional behavior and endocrine regulation. The present data suggest that sex
      specific patterns of proliferating progenitors may represent an important
      mechanism for the development of sex differences of adult brain.

PMID- 23000629
TI  - Protective activity of alpha-lactoalbumin (ALAC), a whey protein rich in
      tryptophan, in rodent models of epileptogenesis.
AB  - The aim of the present work was to evaluate the potential activity of alpha
      lactoalbumin (ALAC), a whey protein rich in tryptophan (TRP), in two rodent
      models of epileptogenesis and we explored a possible mechanism of action. The
      effects of ALAC (oral administration) were tested in two standard epileptogenesis
      protocols, namely the pilocarpine post-status epilepticus model in mice and the
      WAG/Rij rat model of absence epileptogenesis. The mechanism of action was
      investigated by assessing the effects of ALAC in two seizure models (N-methyl-d
      aspartate (NMDA) and pentylenetetrazol (PTZ) -induced seizures) including d
      serine co-administration. ALAC showed protecting properties in both models of
      epileptogenesis, reducing spontaneous seizures development. In acute seizure
      models, ALAC possessed antiseizure properties at some of the doses tested (PTZ
      seizures: >50% seizure-reduction between 250 and 375 mg/kg; NMDA-seizures: >90%
      reduction at 250 and 500 mg/kg). When a dose of d-serine ineffective per se was
      co-administered with ALAC, ALAC effects were significantly reversed in both
      models. ALAC is active in experimental models of seizure and epileptogenesis. Its
      effects are likely mediated by the inhibition of NMDA receptors at the glycine
      binding site, possibly secondarily to the in vivo enzymatic conversion of ALAC
      generated tryptophan to kynurenic acid. However, other mechanisms of action
      contributing to ALAC effects cannot be excluded.

PMID- 23000630
TI  - Glycogen synthase kinase 3-specific inhibitor AR-A014418 decreases neuropathic
      pain in mice: evidence for the mechanisms of action.
AB  - The present study examined the antihyperalgesic effect of a specific inhibitor of
      Glycogen Synthase Kinase 3 (GSK3), AR-A014418, on the partial ligation of the
      sciatic nerve (PSNL), a neuropathic pain model in mice and investigated some
      mechanisms of action. AR-A014418 (0.01-1 mg/kg) administered by intraperitoneal
      route (i.p.) inhibited mechanical hyperalgesia. This action started 30 min after
      i.p. administration and remained significant up to 2 h. When administered daily
      for 5 days, AR-A014418 (0.3 mg/kg, i.p.) significantly reduced the mechanical
      hyperalgesia caused by PSNL. Intraperitoneal (i.p.) treatment with AR-A014418
      (0.3 mg/kg) also significantly inhibited cold hyperalgesia induced by PSNL. Pre
      administration of PCPA (100 mg/kg, i.p., inhibitor of serotonin synthesis) and
      AMPT (100 mg/kg, i.p., inhibitor of tyrosine hydroxylase), but not l-arginine
      (600 mg/kg, i.p., a nitric oxide precursor), significantly reduced the mechanical
      hyperalgesia elicited by AR-A014418. Furthermore, the administration of AR
      A014418 significantly prevented the increase of TNF-alpha (inhibition of 76+/-8%)
      and IL-1beta (inhibition of 62+/-10%), but did not alter lumbar spinal cord IL1
      ra and IL-10 levels. Finally, intraperitoneal administration of AR-A014418 did
      not affect locomotor activity in the open-field test. Taken together, these
      results provide experimental evidence indicating that AR-A014418 produces marked
      antihyperalgesic effects in neuropathic pain in mice, possibly due to mechanisms
      that reduce proinflammatory cytokines, as well as increases in serotonergic and
      catecholaminergic pathways. The present study suggests that GSK3 may be a novel
      pharmacological target for the treatment of neuropathic pain and AR-A014418 might
      be a potential molecule of interest for chronic pain relief.

PMID- 23000631
TI  - A quantitative PCR method for assessing the presence of Pasteurella testudinis
      DNA in nasal lavage samples from the desert tortoise (Gopherus agassizii).
AB  - Pasteurella testudinis has been associated with upper respiratory tract disease
      (URTD) in the threatened desert tortoise (Gopherus agassizii). Our goal was to
      develop a sensitive and specific qPCR method for detecting DNA from P. testudinis
      in nasal lavage fluid collected from desert tortoises in the field. Probes for
      16S ribosomal RNA and RNA polymerase beta-subunit (rpoB) genes were designed. A
      standard curve generated with DNA extracted from known numbers of bacterial cells
      determined by flow cytometry revealed a lower detection limit of 50 fg/ml (10
      bacteria/ml). The nasal lavage fluid contained no interfering substances, and the
      qPCR method did not recognize normal flora DNA. The nasal lavage samples from 20
      desert tortoises captured in Clark County, Nevada, USA in 2007 and housed at the
      Desert Tortoise Conservation Center, were all positive for P. testudinis DNA by
      qPCR. Another set of 19 lavage samples collected in 2010 from wild desert
      tortoises in the Mojave Desert were tested and 84% were positive for P.
      testudinis DNA. Fully validated, this qPCR method will provide a means of
      determining colonization rate. When used in conjunction with serological methods
      and clinical evaluations, both infection rate and disease rate can be determined
      for this potential URTD pathogen. This new assay provides an important tool for
      managing the threatened populations of the Mojave Desert tortoise.

PMID- 23000632
TI  - Enhancing sibling relationships to prevent adolescent problem behaviors: theory,
      design and feasibility of Siblings Are Special.
AB  - Siblings play a significant but neglected role in family socialization dynamics,
      and focusing on the sibling relationship is a non-stigmatizing point of entry
      into the family for prevention programming. Siblings are Special (SAS) was
      designed as a universal program that targets both sibling relationship and
      parenting mediating processes in middle childhood to prevent behavior problems in
      adolescence. We describe the theoretical framework underlying SAS, the SAS
      curriculum, and the feasibility of the program based on a study of 128 middle
      childhood aged sibling dyads. Data on the quality of program implementation,
      program fidelity, siblings' engagement, and ratings of impact indicated the SAS
      program was acceptable to families and schools, that the curriculum could be
      implemented with high fidelity, that siblings and parents participated at high
      levels and were highly engaged, and that, from the perspective of group leaders,
      school administrators and parents, the program had a positive impact on the
      siblings.

PMID- 23000633
TI  - Rituximab-based novel strategies for the treatment of immune-mediated glomerular
      diseases.
AB  - Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was
      initially designed and approved for the treatment of non-Hodgkin's B-cell
      lymphoma in 1997. In the last 15years, it has emerged as a potent
      immunosuppressant for many immune-mediated diseases, beginning initially with
      rheumatoid arthritis, and now extending into several other fields, including
      clinical nephrology. Based on recent large clinical trials, it is FDA-approved
      for the treatment of ANCA-associated vasculitis and continues to be studied in
      off-label usage for many glomerular diseases, including membranous nephropathy,
      lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in
      nephrotic syndrome in children and adults, including both minimal change disease
      and focal segmental glomerulosclerosis. Given its efficacy, tolerability and
      safety profile in comparison to more conventional treatment regimens, RTX is
      rapidly emerging as a critical treatment modality in glomerular disease.

PMID- 23000634
TI  - Clinical characteristics of impaired trunk control in children with spastic
      cerebral palsy.
AB  - This study aimed to identify clinical characteristics of impaired trunk control
      in hundred children with spastic CP (mean age 11.4 +/- 2.1 years, range 8-15
      years). Assessment of trunk control was performed with the Trunk Control
      Measurement Scale (TCMS). Trunk control was clearly impaired, indicated by a
      median total TCMS score of 38.5 out of 58 (66%). Median subscale scores were 18
      out of 20 (90%) for the subscale static sitting balance, 16 out of 28 (57%) for
      the subscale selective movement control and 6 out of 10 (60%) for the subscale
      dynamic reaching. Total TCMS and subscale scores differed significantly between
      topographies and severity of motor impairment according to the Gross Motor
      Function Classification System (GMFCS). Children with hemiplegia obtained the
      highest scores, followed by children with diplegia and children with quadriplegia
      obtained the lowest scores. TCMS scores significantly decreased with increasing
      GMFCS level. In conclusion, trunk control is impaired in children with CP to a
      various extent, depending on the topography and severity of the motor impairment.
      The findings of this study also provide specific clues for treatment
      interventions targeting trunk control to improve their functional abilities.

PMID- 23000635
TI  - Reduced metaboreflex control of blood pressure during exercise in individuals
      with intellectual disability: a possible contributor to exercise intolerance.
AB  - The aim was to investigate the hemodynamic responses to isometric handgrip
      exercise (HG) and examine the role of the muscle metaboreflex in the exercise
      pressor response in individuals with intellectual disability (IID) and non
      disabled control subjects. Eleven males with mild-moderate intellectual
      disabilities and eleven non-disabled males performed a testing protocol involving
      3-min periods of baseline, HG exercise (at 30% MVC), circulatory occlusion, and
      recovery. The same protocol was repeated without occlusion. At baseline, no
      differences were detected between groups in beat-to-beat mean arterial pressure
      (MAP), heart rate (HR), stroke volume, and peripheral resistance. IID were able
      to sustain an exercise MAP response at comparable levels to the control group
      exerting similar peripheral resistance; however, IID exhibited a blunted
      chronotropic response to HG and a diminished exercise vagal withdrawal compared
      to controls. During occlusion, IID exhibited a lower pressor response than their
      control peers, associated with a lower increase in peripheral resistance during
      this task. In conclusion, although intellectual disabilities can be the
      consequence of many different genes, IID share common deficits in the
      chronotropic response to exercise and a blunted metaboreflex-induced pressor
      response.

PMID- 23000636
TI  - Differential cognitive and perceptual correlates of print reading versus braille
      reading.
AB  - The relations between reading, auditory, speech, phonological and tactile spatial
      processing are investigated in a Dutch speaking sample of blind braille readers
      as compared to sighted print readers. Performance is assessed in blind and
      sighted children and adults. Regarding phonological ability, braille readers
      perform equally well compared to print readers on phonological awareness, better
      on verbal short-term memory and significantly worse on lexical retrieval. The
      groups do not differ on speech perception or auditory processing. Braille
      readers, however, have more sensitive fingers than print readers. Investigation
      of the relations between these cognitive and perceptual skills and reading
      performance indicates that in the group of braille readers auditory temporal
      processing has a longer lasting and stronger impact not only on phonological
      abilities, which have to satisfy the high processing demands of the strictly
      serial language input, but also directly on the reading ability itself. Print
      readers switch between grapho-phonological and lexical reading modes depending on
      the familiarity of the items. Furthermore, the auditory temporal processing and
      speech perception, which were substantially interrelated with phonological
      processing, had no direct associations with print reading measures.

PMID- 23000637
TI  - Comprehensive quantification of the spastic catch in children with cerebral
      palsy.
AB  - In clinical settings, the spastic catch is judged subjectively. This study
      assessed the psychometric properties of objective parameters that define and
      quantify the severity of the spastic catch in children with cerebral palsy (CP).
      A convenience sample of children with spastic CP (N=46; age range: 4-16 years)
      underwent objective spasticity assessments. High velocity, passive stretches were
      applied to the gastrocnemius (GAS) and medial hamstrings (MEH). Muscle activity
      was measured with surface electromyography (sEMG), joint angle characteristics
      using inertial sensors and reactive torque using a force sensor. To test
      reliability, a group of 12 children were retested after an average of 13 +/- 9
      days. The angle of spastic catch (AOC) was estimated by three biomechanical
      definitions: joint angle at (1) maximum angular deceleration; (2) maximum change
      in torque; and (3) minimum power. Each definition was checked for reliability and
      validity. Construct and clinical validity were evaluated by correlating each AOC
      definition to the averaged root mean square envelope of EMG (RMS-EMG) and the
      Modified Tardieu Scale (MTS). Severity categories were created based on selected
      parameters to establish face validity. All definitions showed moderate to high
      reliability. Significant correlations were found between AOC3 and the MTS of both
      muscles and the RMS-EMG of the MEH, though coefficients were only weak. AOC3
      further distinguished between mild, moderate and severe catches. Objective
      parameters can define and quantify the severity of the spastic catch in children
      with CP. However, a comprehensive understanding requires the integration of both
      biomechanical and RMS-EMG data.

PMID- 23000639
TI  - From the editor.

PMID- 23000640
TI  - Subjective illness perceptions in individuals with occupational skin disease: a
      qualitative investigation.
AB  - OBJECTIVE: Occupational skin disease (OSD) is the most frequent work-related
      disease in most industrialised countries and poses a high social, economic and
      personal burden. However, to date no study has examined the illness perceptions
      of individuals with refractory OSD. PARTICIPANTS AND METHODS: Semi-structured
      guided interviews with 50 patients with OSD were conducted. Data was subjected to
      qualitative content analysis. RESULTS: Most patients were not able to see the
      prodromal symptom-character of dry skin or the involvement of psychological
      factors in the formation and maintenance of eczema. Patients rejected a personal
      accountability for the condition. Before being willing to act upon skin
      protection measures, external agencies (employer, insurance organisations) have
      to overcome a variety of perceived barriers. Previous negative experiences with
      skin protection often lead to the conclusion that these measures, in general, are
      not efficacious. CONCLUSIONS: In order to accommodate the needs of patients with
      OSD, health care providers need to be aware of what these patients' illness
      cognitions consist of, and how they interact with current preventive efforts.
      Many details of the patient's perspective are often overlooked, but need to be
      considered. Failure to do so may mean that well-meant interventions will not
      reach the addressed audience successfully.

PMID- 23000638
TI  - TFIIIC bound DNA elements in nuclear organization and insulation.
AB  - tRNA genes (tDNAs) have been known to have barrier insulator function in budding
      yeast, Saccharomyces cerevisiae, for over a decade. tDNAs also play a role in
      genome organization by clustering at sites in the nucleus and both of these
      functions are dependent on the transcription factor TFIIIC. More recently TFIIIC
      bound sites devoid of pol III, termed Extra-TFIIIC sites (ETC) have been
      identified in budding yeast and these sites also function as insulators and
      affect genome organization. Subsequent studies in Schizosaccharomyces pombe
      showed that TFIIIC bound sites were insulators and also functioned as Chromosome
      Organization Clamps (COC); tethering the sites to the nuclear periphery. Very
      recently studies have moved to mammalian systems where pol III genes and their
      associated factors have been investigated in both mouse and human cells. Short
      interspersed nuclear elements (SINEs) that bind TFIIIC, function as insulator
      elements and tDNAs can also function as both enhancer - blocking and barrier
      insulators in these organisms. It was also recently shown that tDNAs cluster with
      other tDNAs and with ETCs but not with pol II transcribed genes. Intriguingly,
      TFIIIC is often found near pol II transcription start sites and it remains
      unclear what the consequences of TFIIIC based genomic organization are and what
      influence pol III factors have on pol II transcribed genes and vice versa. In
      this review we provide a comprehensive overview of the known data on pol III
      factors in insulation and genome organization and identify the many open
      questions that require further investigation. This article is part of a Special
      Issue entitled: Transcription by Odd Pols.

PMID- 23000641
TI  - Isolation and functional characterization for oocyte maturation and sperm
      motility of the oocyte maturation arresting factor from the Japanese scallop,
      Patinopecten yessoensis.
AB  - In bivalves, serotonin (5-hydroxytriptamine, 5-HT) acts as a major promotional
      factor in oocyte maturation, sperm motility, and sequential spawning. The
      previously reported novel neuronal protein, oocyte maturation arresting factor
      (OMAF) that was found in the central nervous system and hemolymph of the Japanese
      scallop, Patinopecten yessoensis, has an inhibitory activity in the 5-HT-induced
      oocyte maturation via a receptor-mediated mechanism, resulting in an arrest of
      spawning [30]. In this study, OMAF protein was isolated from the supernatant of
      hemolymph of the scallop using gel and anion-exchange chromatography, and SDS
      PAGE. Three digested partial peptides with 4, 11, and 16 amino acid residues were
      determined through reversed-phase HPLC and amino acid sequencing. The anti-OMAF
      antibodies generated against the obtained peptides with 11 and 16 amino acid
      residues were applied to immunohistochemistry and 5-HT-induced spawning and
      oocyte maturation assays. Fusiform OMAF neurons were localized in the external
      area of the anterior lobe of the cerebral ganglion, supporting our presumption
      that OMAF was secreted from the cerebral and pedal ganglia (CPG). Pretreatment
      with anti-OMAF antibody on three kinds of bivalve species showed a strong in vivo
      amplification of 5-HT-induced release of egg and sperm, and an in vitro
      restoration of 5-HT-induced germinal vesicle breakdown (GVBD) from inhibition by
      the CPG extract, suggesting the release from suppressive activity of OMAF due to
      the absorption with antibody. These results confirm that the isolated peptides
      are from OMAF and OMAF acts as an inhibitor of 5-HT-induced oocyte maturation and
      sperm motility as previously reported.

PMID- 23000642
TI  - HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review
      and meta-analysis.
AB  - Reactivation of human herpesvirus-6 (HHV-6) frequently occurs following
      hematopoietic SCT (HSCT), and has been associated with clinical consequences in
      many patient populations. HHV-6 reactivation and HHV-6 encephalitis seem to occur
      more frequently in patients undergoing HSCT with cord blood (CB) as the stem cell
      source. We have conducted a systematic literature review and meta-analysis to
      investigate the clinical significance of this correlation. A systematic review of
      publications indexed in PubMed was performed for HSCT studies published over the
      past 10 years that fit inclusion criteria. Data on prevalences of HHV-6
      reactivation and HHV-6 encephalitis post HSCT were abstracted from 19 papers.
      Meta-analyses were conducted to calculate combined prevalence estimates. The
      prevalences of HHV-6 reactivation and encephalitis were compared among CB vs non
      CB HSCT. Prevalences of HHV-6 reactivation and HHV-6 encephalitis were
      significantly higher in patients receiving CB as the stem cell source than in
      patients receiving another stem cell source (72.0% vs 37.4%, P<0.0001; 8.3% vs
      0.50%, P<0.0001, respectively). HHV-6 reactivation and HHV-6 encephalitis are
      significant complications in the post-HSCT setting, particularly in patients
      receiving CB as the stem cell source. Thus, patients undergoing umbilical CB
      transplantation should be closely monitored for HHV-6 reactivation.

PMID- 23000643
TI  - Intravenous ribavirin for respiratory syncytial viral infections in pediatric
      hematopoietic SCT recipients.
AB  - Respiratory syncytial virus (RSV) is a potential cause of serious morbidity and
      even mortality among children undergoing hematopoietic SCT (HSCT). Contrary to
      the available information regarding the aerosolized formulation of ribavirin,
      there is a paucity of published studies using i.v. ribavirin in adults, and very
      few single reports on pediatric patients. Aerosolized drug administration has
      been limited by potential toxicity and special air-flow requirements. In this
      regard, i.v. ribavirin could prevent these disadvantages, but its efficacy and
      safety remain controversial in the pediatric HSCT setting. The present study
      describes the outcome of six pediatric patients undergoing HSCT with nine
      episodes of proven RSV. Four episodes corresponded to lower respiratory tract
      infection (LRTI) and five presented with upper respiratory tract infection
      (URTI). All LRTI patients showed favorable clinical responses, with 100% survival
      and no progression to LRTI in the remaining five URTI. No side effects were
      documented during ribavirin administration. We conclude that ribavirin was well
      tolerated intravenously, without associated side effects, and was effective in
      the treatment of RSV in this limited number of pediatric HSCT patients. The role
      and efficacy of i.v. ribavirin needs to be further clarified by prospective
      controlled trials in pediatric populations.

PMID- 23000644
TI  - A phase II study of sirolimus, tacrolimus and rabbit anti-thymocyte globulin as
      GVHD prophylaxis after unrelated-donor PBSC transplant.
AB  - We report on a prospective phase II trial of 32 patients who underwent unrelated
      donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit
      anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was
      incidence of grades II-IV acute (aGVHD), with 80% power to detect a 30% decrease
      compared with institutional historical controls. Median age at transplant was 60
      (19-71). In total, 23 patients (72%) received reduced-intensity conditioning,
      whereas the remainder received full-intensity regimens. Median follow-up for
      surviving patients was 35 months (range: 21-49). The cumulative incidence of
      aGVHD was 37.3%, and the 2-year cumulative incidence of chronic GVHD was 63%. We
      observed thrombotic microangiopathy in seven patients (21.8%), one of whom also
      developed sinusoidal obstructive syndrome (SOS). Four of the 32 patients (12.5%)
      failed to engraft, and 3 of these 4 died. As a result, enrollment to this trial
      was closed before the targeted accrual of 60 patients. Two-year OS was 65.5% and
      EFS was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse
      mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates.
      However, the unexpectedly high incidence of graft failure requires caution in the
      design of future studies with this regimen.

PMID- 23000646
TI  - Resolution of macular oedema associated with retinitis pigmentosa after
      intravitreal use of autologous BM-derived hematopoietic stem cell
      transplantation.

PMID- 23000645
TI  - Risk and prognostic factors for acute GVHD based on NIH consensus criteria.
AB  - To investigate the risk factors for acute GVHD (aGVHD), based on NIH consensus
      criteria (NCC), we evaluated 775 patients who underwent allogeneic
      transplantation. Of them, 346 patients developed aGVHD by NCC, in whom we also
      analyzed factors affecting aGVHD-specific survival. The cumulative incidence of
      aGVHD was 44.7%, consisting of classic aGVHD (n=320) and late-onset (n=26).
      Multivariate analyses revealed that younger age (P=0.015), unrelated donors
      (P=0.004) and acute leukemia compared with other hematologic malignancies
      (P=0.005) were significant risk factors for aGVHD, whereas PBSCs showed no
      association (P=0.720). Multivariate analyses, with only aGVHD patients, revealed
      that late-onset aGVHD had superior aGVHD-specific survival to classic aGVHD
      (P=0.044), and identified the association of visceral organ involvement
      (P=0.002), severity of aGVHD at onset (P=0.035) and advanced disease status
      (P<0.001) with inferior aGVHD-specific survival. In conclusion, this study
      demonstrates the risk and prognostic factors for aGVHD by NCC with some
      differences with the previous reports that were based on old criteria. The
      difference in the risk factors according to different criteria will give insights
      about the pathophysiology of GVHD. The better prognosis of late-onset aGVHD than
      of classic aGVHD raises the necessity for prospective trials with a large cohort
      focusing on the onset time.

PMID- 23000647
TI  - Second auto-SCT for treatment of relapsed multiple myeloma.
AB  - High-dose therapy and auto-SCT remain integral in the initial treatment of
      multiple myeloma (MM), and are increasingly being applied for management of
      relapsed disease. We examined the outcomes in 98 patients undergoing salvage auto
      SCT (auto-SCT2) for relapsed MM after receiving an initial transplant (auto-SCT1)
      between 1994 and 2009. The median age at auto-SCT2 was 60 years (range: 35-74).
      The median time between auto-SCT1 and auto-SCT2 was 46 months (range: 10-130).
      Treatment-related mortality was seen in 4%. The median PFS from auto-SCT2 was
      10.3 (95% confidence interval (CI): 7-14) months and the median OS from auto-SCT2
      was 33 months (95% CI: 28-51). In a multivariable analysis, shorter time to
      progression (TTP) after auto-SCT1, not achieving a CR after auto-SCT2, higher
      number of treatment regimens before auto-SCT2 and a higher plasma cell labeling
      index at auto-SCT2 predicted for shorter PFS. However, only a shorter TTP after
      auto-SCT1 predicted for a shorter OS post auto-SCT2. Hence, auto-SCT2 is an
      effective and feasible therapeutic option for MM patients relapsing after other
      treatments, especially in patients who had a TTP of at least 12 months after
      their auto-SCT1.

PMID- 23000648
TI  - Peri-engraftment syndrome in allogeneic hematopoietic SCT.
AB  - Engraftment syndrome (ES) and pre-engraftment syndrome (pre-ES) are both
      inflammatory conditions that occur after hematopoietic SCT (HSCT) and are
      characterized by non-infectious fever and skin rash. Although the pathogenesis is
      not fully understood, both syndromes are similar, and could be defined as a new
      clinical syndrome, named as peri-engraftment syndrome (peri-ES). We
      retrospectively analyzed the clinical records in 176 pediatric patients,
      following allogeneic HSCT. We utilized the definition of ES by Spitzer as the
      diagnostic criteria, excluding 'within 96 h of engraftment' criteria. Thirty
      cases developed peri-ES with a cumulative incidence of 17.0%. High cumulative
      incidence (50%) was seen in patients who underwent a double-unit cord blood
      transplantation (DUCBT; P<0.01). Clinical findings of peri-ES are similar,
      regardless of the onset day, and encephalopathy was the most severe complication.
      In the DUCBT cohort, the use of TBI and early complete chimerism (<= day 21) were
      identified as risk factors that predispose the development of peri-ES. We
      determined that both, ES and pre-ES, might have similar causes, which could be
      included in peri-ES. Particularly, it occurred more in DUCBT patients, which
      means that not only neutrophil engraftment but also immune reactions within the
      two units might contribute to peri-ES.

PMID- 23000649
TI  - Topical thalidomide gel in oral chronic GVHD and role of in situ cytokine
      expression in monitoring biological activity.

PMID- 23000650
TI  - Alternative donor SCT for the treatment of MHC class II deficiency.
AB  - MHC Class II deficiency is a rare primary immunodeficiency disease characterized
      by absent HLA Class II expression resulting in CD4 lymphopenia, lack of Ag
      specific responses and recurrent infection. Without successful allogeneic SCT,
      most children succumb to infection within the first decade of life. To date,
      alternative donor transplants for this disorder have been inferior to SCT for
      other forms of combined immunodeficiency disease due to an increased incidence of
      graft rejection, GVHD and death from infections generally acquired before
      haematopoietic cell transplantation. This study details the transplant outcome of
      16 affected children consecutively transplanted at four centers since 1990, 8 of
      whom required mechanical ventilation pretransplant. Stem cells were derived from
      an HLA-mismatched family member (n=10), an HLA-matched unrelated adult donor
      (n=4), or an unrelated cord blood donor (n=2). Graft failure occurred in five
      children, all of whom underwent a second SCT. Six patients developed acute GVHD
      although no patient developed chronic GVHD after primary transplantation. CD4 T
      cell reconstitution remained below the normal range for age, suggesting defective
      thymopoiesis after allo-SCT. Nonetheless, 69% of children survive without GVHD at
      a median follow-up of 5.7 years, indicating improved outcomes compared with
      previous studies.

PMID- 23000651
TI  - Efficacy of allogeneic and autologous hematopoietic SCT in patients with AML
      after first complete remission.
AB  - The most effective post-first CR1 treatment for patients with AML, allogenic
      hematopoietic SCT (allo-HSCT) or autologous hematopoietic SCT (HSCT), remains to
      be conclusively determined. This study aimed to compare the effectiveness of
      treatment with allo-HSCT or auto-HSCT in patients with AML after CR1. We
      retrospectively reviewed medical records of 127 patients with AML who received
      allo- (n=52) or auto-HSCT (n=75) after achieving CR1 at a single medical center.
      The disease-free and overall survival rates and complications were analyzed.
      During a median follow-up of 1215 days, all patients (100%) in allo-HSCT group
      and 94.7% of patients in the auto-HSCT group had successful outcomes. The disease
      free survival rates were 65.3% and 50.6% for allo- and auto-HSCT groups,
      respectively (P=0.158), while the overall survival rates were 65.3% and 54.9%,
      respectively (P=0.486). The recurrence rate was higher with auto-HSCT, whereas
      the GVHD only happened with allo-HSCT. In conclusion, auto-HSCT was as effective
      as allo-HSCT for the treatment of patients with AML after CR1. This is
      encouraging given that allo-HSCT is not always feasible in China because of a
      lack of matching donors.

PMID- 23000652
TI  - Stem cell source-dependent reconstitution of FOXP3+ T cells after pediatric SCT
      and the association with allo-reactive disease.
AB  - In adult patients, regulatory CD4+FOXP3+ T cells are suggested to have a role in
      the control of allo-reactive disease after hematopoietic SCT (HSCT). We compared
      CD4+FOXP3+ T-cell reconstitution after unrelated cord blood (UCB), matched
      unrelated donor (MUD) and matched sibling donor (MSD) HSCT in children, starting
      as early as 1 week after transplantation, and analyzed the association with allo
      reactive disease. A total of 30 children were included who underwent a
      myeloablative-conditioning regimen followed by UCB (12/30), MUD (7/30) or MSD
      (11/30) HSCT. These three patient groups showed significant differences in FOXP3+
      T-cell reconstitution pattern. Early after UCB and MSD, but not after MUD, HSCT a
      peak in FOXP3+ T cells was observed. There were significant differences in
      activation status and Ki67 expression of the FOXP3+ T cells after UCB and MSD,
      respectively. FOXP3+ T-cell proportions early after HSCT and in the graft were
      inversely correlated with allo-reactivity. This study indicates that FOXP3
      reconstitution after HSCT is dependent on the type of graft used. Furthermore, in
      children evaluation of FOXP3+ T-cell numbers early after HSCT and in the graft
      may be used to judge the risk of developing allo-reactivity after HSCT.

PMID- 23000653
TI  - Reappraising the role of autologous transplantation for indolent B-cell lymphomas
      in the chemoimmunotherapy era: is it still relevant?
AB  - The role of autologous hematopoietic cell transplantation (auto-HCT) in the
      management of indolent non-Hodgkin lymphomas (NHL) is shrouded in controversy.
      The outcomes of conventional therapies for many indolent lymphoma subtypes have
      dramatically improved over the last several years with the use of monoclonal
      antibodies, maintenance therapy programs and with the incorporation of radio
      immunoconjugates. These significant advances in the armamentarium of lymphoma
      therapeutics warrant reappraisal of the current role of auto-HCT in the treatment
      algorithm of indolent NHL. Prospective randomized studies comparing contemporary
      chemoimmunotherapies against auto-HCT are lacking, leading to significant debate
      about the role and timing of auto-HCT for indolent NHL in the modern era.
      Although autografting for follicular lymphoma (FL) in first remission has been
      largely abandoned, it remains a useful modality for relapsed disease, especially
      for the subgroup of patients who are not candidates for allogeneic
      transplantation with a curative intent. Auto-HCT can provide durable disease
      control in chemosensitive transformed FL and mantle cell lymphoma (MCL) in first
      remission, with relatively low toxicity, and remains appropriate in
      chemoimmunotherapy era. Contemporary data are also reviewed to clarify the often
      underutilized role of autografting in relapsed MCL and other less frequent
      indolent NHL histologies. The biological basis of the increased risks of second
      malignancies with auto-HCT are reviewed to identify strategies designed to
      mitigate this risk by, for example, avoiding exposure to genotoxic agents,
      planning early stem cell collection/cryopreservation and minimizing the use of
      TBI with transplant conditioning, and so on. Genetic testing able to identify
      patients at high risk of therapy-related complications and novel post-transplant
      immune therapies with the potential of transforming autografting in indolent NHL
      from a remission-extending therapy to a curative modality are discussed to
      examine the possibly expanding role of auto-HCT for lymphoid malignancies in the
      coming years. 

PMID- 23000654
TI  - Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate
      with the development of chronic GVHD.
AB  - Vitamin D, a hormone involved in bone and calcium homeostasis, has been shown to
      have potent immunomodulatory effects. We performed a retrospective cohort
      analysis to evaluate whether monohydroxyvitamin D levels before allogeneic
      hematopoietic SCT (HSCT) correlate with the risk of GVHD. Fifty-three patients
      who underwent myeloablative HSCT were studied. Vitamin D levels were measured in
      serum samples obtained before HSCT. The median 25-hydroxyvitamin vitamin D level
      was 21.9 ng/mL (7.8-45.7). The cumulative incidence (CI) of grades II-IV acute
      GVHD at 100 days was 53.1% in patients with vitamin D<25, versus 33.3% in
      patients with vitamin D >= 25 ng/mL (P=0.13). The CI of chronic GVHD (cGVHD) at 2
      years in patients with vitamin D<25 was 63.8%, compared with 23.8% in patients
      with vitamin D >= 25 ng/mL (P=0.009). Similarly, the 2 year CI of extensive cGVHD
      was significantly greater in patients with vitamin D<25 compared with those with
      vitamin D >= 25 ng/mL (54.5% versus 14.3%, P=0.005). In a multivariable competing
      risk model, low pre-transplant vitamin D levels remained a significant factor
      associated with cGVHD (hazard ratio=5.26, P=0.02). Our results demonstrate that
      vitamin D deficiency before HSCT is associated with an increased risk of cGVHD.

PMID- 23000655
TI  - Fetal maternal immunity and antileukemia activity in cord-blood transplant
      recipients.

PMID- 23000656
TI  - Re: Meta-analysis of efficacy of interventions elevated depressive symptoms in
      adults diagnosed with cancer.

PMID- 23000657
TI  - A missing link between complex I and group 4 membrane-bound [NiFe] hydrogenases.
AB  - Complex I of respiratory chains is an energy transducing enzyme present in most
      bacteria, mitochondria and chloroplasts. It catalyzes the oxidation of NADH and
      the reduction of quinones, coupled to cation translocation across the membrane.
      The complex has a modular structure composed of several proteins most of which
      are identified in other complexes. Close relations between complex I and group 4
      membrane-bound [NiFe] hydrogenases and some subunits of multiple resistance to pH
      (Mrp) Na(+)/H(+) antiporters have been observed before and the suggestion that
      complex I arose from the association of a soluble nicotinamide adenine
      dinucleotide (NAD(+)) reducing hydrogenase with a Mrp-like antiporter has been
      put forward. In this article we performed a thorough taxonomic profile of
      prokaryotic group 4 membrane-bound [NiFe] hydrogenases, complexes I and complex I
      like enzymes. In addition we have investigated the different gene clustering
      organizations of such complexes. Our data show the presence of complexes related
      to hydrogenases but which do not contain the binding site of the catalytic
      centre. These complexes, named before as Ehr (energy-converting hydrogenases
      related complexes) are a missing link between complex I and group 4 membrane
      bound [NiFe] hydrogenases. Based on our observations we put forward a different
      perspective for the relation between complex I and related complexes. In addition
      we discuss the evolutionary, functional and mechanistic implications of this new
      perspective. This article is part of a Special Issue entitled: The evolutionary
      aspects of bioenergetic systems.

PMID- 23000658
TI  - Preparation, structural analysis and bioactivity of ribonuclease A-albumin
      conjugate: tetra-conjugation or PEG as the linker.
AB  - Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against
      tumor cells. Its clinical application is limited by the short half-life and
      insufficient stability. Conjugation of albumin can overcome the limitation,
      whereas dramatically decrease the enzymatic activity of RNase A. Here, three
      strategies were proposed to prepare the RNase A-bovine serum albumin (BSA)
      conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R
      PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional
      linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and
      hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA
      was adopted to bind BSA. The PEG linker can elongate the proximity between RNase
      A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R
      SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and
      k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of
      RNase A in R-SMCC-B can increase the binding affinity to its substrate. In
      addition, the slow release of BSA from R-HDA-B may increase the enzymatic
      activity of R-HDA-B. Our study is expected to provide strategies to develop
      protein-albumin conjugate with high therapeutic potential.

PMID- 23000660
TI  - Aspirin for primary prevention of CVD: are the right people using it?
AB  - PURPOSE: Aspirin is recommended for the primary prevention of cardiovascular
      disease (CVD) in adults at high risk, but little is known about sociodemographic
      disparities in prophylactic aspirin use. This study examined the association
      between sociodemographic characteristics and regular aspirin use among adults in
      Wisconsin who are free of CVD. METHODS: A cross-sectional design was used, and
      data collected from 2008 to 2010. Regular aspirin use (aspirin therapy) was
      defined as taking aspirin most days of the week. We found 831 individuals for
      whom complete data were available for regression analyses and stratified the
      sample into 2 groups: those for whom aspirin therapy was indicated and those for
      whom it was not indicated, based on national guidelines. RESULTS: Of the 268
      patients for whom aspirin therapy was indicated, only 83 (31%) were using it
      regularly, and 102 (18%) of the 563 participants who did not have an aspirin
      indication were taking it regularly. In the group with an aspirin indication,
      participants who were older had higher rates of regular aspirin use than younger
      patients (odds ratio [OR]=1.07; P<.001), and women had significantly higher
      adjusted odds of regular aspirin use than men (OR=3.49; P=.021). Among those for
      whom aspirin therapy was not indicated, the adjusted odds of regular aspirin use
      were significantly higher among older participants (OR=1.07; P<.001) vs their
      younger counterparts, and significantly lower among Hispanic or nonwhite
      participants (OR=0.32; P=.063) relative to non-Hispanic whites. CONCLUSIONS:
      Aspirin therapy is underused by those at high risk for CVD-individuals who could
      gain cardioprotection from regular use-and overused by those at low risk for CVD,
      for whom the risk of major bleeding outweighs the potential benefit. Stronger
      primary care initiatives may be needed to ensure that patients undergo regular
      screening for aspirin use, particularly middle-aged men at high CVD risk. Patient
      education may be needed, as well, to better inform people (particularly older,
      non-Hispanic whites) about the risks of regular aspirin use that is not medically
      indicated.

PMID- 23000661
TI  - Diagnostic puzzler: hypertension in teen.

PMID- 23000662
TI  - Managing incontinence: a 2-visit approach.

PMID- 23000663
TI  - Onychomycosis: a simpler in-office technique for sampling specimens.
AB  - BACKGROUND: In onychomycosis, proper specimen collection is essential for an
      accurate diagnosis and initiation of appropriate therapy. Several techniques and
      locations have been suggested for specimen collection. OBJECTIVE: To investigate
      the optimal technique of fungal sampling in onychomycosis. METHODS: We reexamined
      106 patients with distal and lateral subungual onychomycosis (DLSO) of the
      toenails. (The diagnosis had previously been confirmed by a laboratory
      mycological examination-both potassium hydroxide [KOH] test and fungal culture-of
      samples obtained by the proximal sampling approach.) We collected fungal
      specimens from the distal nail bed first, and later from the distal underside of
      the nail plate. The collected specimens underwent laboratory mycological
      examination. RESULTS: KOH testing was positive in 84 (79.2%) specimens from the
      distal nail bed and only in 60 (56.6%) from the distal underside of the nail
      plate (P=.0007); cultures were positive in 93 (87.7%) and 76 (71.7%) specimens,
      respectively (P=.0063). Combining results from both locations showed positive KOH
      test results in 92 (86.8%) of the 106 patients and positive cultures in 100
      (94.3%) patients. CONCLUSIONS: Based on our study, we suggest that in cases of
      suspected DLSO, material should be obtained by scraping nail material from the
      distal underside of the nail and then collecting all the material from the distal
      part of the nail bed.

PMID- 23000664
TI  - DEXA screening--are we doing too much?

PMID- 23000665
TI  - Sudden onset of generalized scaly eruptions.

PMID- 23000666
TI  - Clinical inquiries. Do antibiotics improve outcomes for patients hospitalized
      with COPD exacerbations?

PMID- 23000668
TI  - Chronic pain perspectives: Managing chronic pain in older adults: 6 steps to
      overcoming medication barriers.
AB  - These practical tips will help improve the likelihood of a successful analgesic
      trial in patients 65 and older.

PMID- 23000667
TI  - Easing the discomfort of a speculum exam.

PMID- 23000669
TI  - Chronic pain perspectives: Sickle cell disease: Gaining control over the pain.
AB  - Ongoing adjustments to the medication regimen and careful attention to lifestyle
      and support systems are critical to helping patients manage the pain of sickle
      cell disease.

PMID- 23000670
TI  - Chronic pain perspectives: Treating herpes zoster and postherpetic neuralgia: an
      evidence-based approach.
AB  - When are corticosteroids appropriate for patients with herpes zoster? Which
      tricyclics are best for frail and elderly patients with PHN pain? And when should
      you consider opioids?

PMID- 23000671
TI  - Initial experience with magnetic resonance imaging of atrial scar and co
      registration with electroanatomic voltage mapping during atrial fibrillation:
      success and limitations.
AB  - BACKGROUND: Ablation for atrial fibrillation (AF) frequently requires multiple
      procedures to achieve durable restoration of sinus rhythm. Early studies have
      suggested that delayed enhancement magnetic resonance imaging (DE-MRI) of the
      left atrium (LA) can assist in performing repeat ablation procedures. OBJECTIVE:
      The purpose of this study was to investigate the utility of DE-MRI in delineating
      regions of LA low voltage and PV reconnection sites in patients undergoing repeat
      PV isolation for recurrent AF. METHODS: We enrolled 10 patients undergoing repeat
      ablation for AF recurrence to undergo preprocedural DE-MRI of the LA in
      conjunction with high-density voltage mapping (>100 sites) of the LA during the
      ablation procedure. LA wall regions with hyperenhancement were segmented from DE
      MRI images and retrospectively co-registered with the electroanatomic LA map. The
      association between scar on DE-MRI images and low-voltage regions of the LA was
      assessed, as was the association between scar gaps and electrogram-determined PV
      reconnection sites. RESULTS: Ten patients underwent successful DE-MRI imaging and
      repeat AF ablation without complication. In all 10 patients, the majority of PVs
      were found to have regained electrical continuity with the LA (30/37 PVs
      electrically active); all patients underwent successful reisolation of all PVs
      using standard ablation techniques. There was a significant association between
      scar identified by DE-MRI and low-voltage regions of the LA (-0.7+/-0.1 mV in
      scar regions; generalized estimating equations model clustered by patient,
      P<.001). However, there was no association between scar gaps and PV reconnection
      sites. CONCLUSION: We demonstrate the co-registration of DE-MRI scar imaging and
      electroanatomic LA mapping, with agreement between regions of scar on DE-MRI and
      low voltage by mapping. However, at our center, this technique did not provide
      accurate information on the location of PV reconnection sites in patients
      undergoing repeat ablation for AF.

PMID- 23000672
TI  - Acute pancreatitis complicated by infected pseudocyst in a child with pancreas
      divisum.
AB  - INTRODUCTION: Acute pancreatitis occurs less frequently in children than in
      adults, although it seems to be more common than has been considered in the past.
      There are several causes of pancreatitis in childhood: trauma, infections or
      structural gland anomalies as pancreas divisum. CASE PRESENTATION: We report a
      case of non-traumatic severe acute pancreatitis in a 8-year-old girl with
      pancreas divisum, complicated by a rapid formation of a large infected pseudocyst
      which required a surgical internal drainage by a Roux-en-Y cystojejunostomy.
      DISCUSSION: Pancreas divisum is the most common congenital anomaly of the
      pancreas with an incidence of 3-10% of population, and its role in causing acute
      or recurrent pancreatitis is still controversial. There are only sporadic
      observations of acute pancreatitis complicated by pseudocyst in children with
      pancreatic anomalies and its treatment is not standardized. Three different
      approaches have been described to treat a pancreatic pseudocyst: percutaneous,
      endoscopic or surgical drainage. We decided to perform a pseudocyst-jejunostomy
      because of the disease severity. CONCLUSION: Even in the non-invasive era, the
      surgical approach to treat a large complicated pseudocysts in children still
      represents a safe and feasible approach in emergencies as acute abdomen, bleeding
      or sepsis. Complications of percutaneous and endoscopic drainages are avoided and
      long term results are excellent. KEY WORDS: Acute pancreatitis, Pancreas divisum,
      Pancreatic pseudocyst.

PMID- 23000673
TI  - Motor dysfunction and cerebellar Purkinje cell firing impairment in Ebf2 null
      mice.
AB  - Mice deficient for the transcription factor Ebf2 lose a subset of Purkinje cells
      during development and have a hypotrophic cerebellar cortex. Related motor
      symptoms and the function of Purkinje cells surviving in the adult have not been
      studied so far. Ebf2 null mice presented locomotor impairment and a deficiency of
      motor coordination and motor learning. Ebf2 null Purkinje cells of the anterior
      lobe, relative to wild-type controls, were patch-clamp recorded in acutely
      prepared slices. While immature Purkinje cells (10-20 postnatal days) of Ebf2
      null mice showed no significant difference relative to wild-types, in the adult
      they featured a higher input resistance, increased anomalous rectification,
      decreased first spike latency, higher initial firing frequency, lower voltage
      threshold and reduced afterhyperpolarizations and post-burst hyperpolarizations.
      These parameters indicate a difference in the response to both hyperpolarizing
      and depolarizing stimuli, corresponding to an altered cerebellar cortical output
      signaling. In contrast, adult climbing fibers attained a normal monoinnervation
      pattern and the parallel fiber-Purkinje cell synapse showed evoked postsynaptic
      currents and paired-pulse facilitation functionally indistinguishable from wild
      type PCs. These results suggest that the motor deficits exhibited by Ebf2 null
      mice could be due, at least in part, to an impairment of the firing properties of
      surviving Purkinje cells. These findings indicate that Ebf2 is important for the
      development and maintenance of normal Purkinje cell discharge properties.

PMID- 23000674
TI  - In vitro culture systems for the study of apicomplexan parasites in farm animals.
AB  - In vitro culture systems represent powerful tools for the study of apicomplexan
      parasites such as Cryptosporidium, Eimeria, Sarcocystis, Neospora, Toxoplasma,
      Besnoitia, Babesia and Theileria, all with high relevance for farm animals.
      Proliferative stages of these parasites have been cultured in vitro employing a
      large variety of cell culture and explant approaches. For some, such as
      Cryptosporidium and Eimeria, the sexual development has been reproduced in cell
      cultures, while for others, animal experimentation is required to fulfill the
      life cycle. In vitro cultures have paved the way to exploit the basic biology of
      these organisms, and had a major impact on the development of tools for
      diagnostic purposes. With the aid of in vitro cultivation, studies on host
      parasite interactions, on factors involved in innate resistance, stage conversion
      and differentiation, genetics and transfection technology, vaccine candidates and
      drug effectiveness could be carried out. The use of transgenic parasites has
      facilitated high-throughput screening of anti-microbial compounds that are active
      against the proliferative stages. Here, we review the basic features of cell
      culture-based in vitro systems for apicomplexan parasites that are relevant for
      farm animals, and discuss their applications with a focus on drug identification
      and studies of stage differentiation.

PMID- 23000675
TI  - PEG-chitosan-coated iron oxide nanoparticles with high saturated magnetization as
      carriers of 10-hydroxycamptothecin: preparation, characterization and
      cytotoxicity studies.
AB  - A magnetic nano-sized carrier for 10-hydroxycamptothecin (HCPT) was prepared by
      using Fe(3)O(4) nanoparticles as cores and chitosan (CS) as a polymeric shell by
      a novel reverse ultrasonic emulsification method. Poly(ethylene glycol) (PEG)
      chains were then coupled onto the magnetic particles (CS-Fe(3)O(4)) to improve
      their biocompatibility (PEG-CS-Fe(3)O(4)). HCPT was loaded onto PEG-CS-Fe(3)O(4)
      by a subtle precipitation method. Under optimum conditions, the CS-Fe(3)O(4) was
      close to spherical in shape with an average size of 174 nm and a high saturated
      magnetization. After coupling PEG chains, the unspecific adsorption of bovine
      serum albumin (BSA) on PEG-CS-Fe(3)O(4) decreased significantly. The drug loading
      content and loading efficiency were 9.8-11.8% and 49-59% for magnetic composite
      nanoparticles, respectively. HCPT-loaded magnetic composite nanoparticles showed
      sustained release profiles up to 48 h, and the cumulative release amount of HCPT
      from nanoparticles at 45 degrees C increased significantly compared to that at 37
      degrees C. Cytotoxicity assay suggests that CS-Fe(3)O(4) does not exhibit
      noteworthy cytotoxicity against HepG2 cells, but the antitumor activities of HCPT
      loaded magnetic composite nanoparticles against HepG2 cells increased
      significantly in comparison with that of pristine HCPT powder. These results
      reveal the promising potential of PEG-CS-Fe(3)O(4) as a stable magnetic targeting
      drug carrier in cancer therapy.

PMID- 23000676
TI  - Functionalized polypropylene non-woven fabric membrane with bovine serum albumin
      and its hemocompatibility enhancement.
AB  - Bovine serum albumin (BSA) was successfully immobilized onto polypropylene non
      woven fabric (PP(NWF)) membranes using poly(acrylic acid) (PAA) as a spacer.
      Firstly, O(2) plasma treatment and UV-irradiated technique were combined to graft
      PAA onto the membranes. BSA was then immobilized onto the PAA grafted surface
      through the coupling of amino groups of BSA to the carboxyl groups of PAA. The
      immobilization of PAA and BSA onto the membrane was confirmed by attenuated total
      reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray
      photoelectron spectroscopy (XPS), and water contact angle measurement. The water
      contact angle measurement results revealed that the membrane hydrophilicity
      improved after modification with PAA and BSA. After BSA immobilization, the
      amount of protein adsorption and the number of platelet adhesion on the modified
      membrane significantly decreased, which indicated that hemocompatibility had been
      considerably improved compared with neat and PAA grafted PP(NWF). The whole blood
      clotting time measurement showed that the anticoagulant property of the modified
      membrane was also significantly enhanced.

PMID- 23000677
TI  - Topical delivery of clobetasol propionate loaded microemulsion based gel for
      effective treatment of vitiligo: ex vivo permeation and skin irritation studies.
AB  - The aim of the present investigation was to evaluate microemulsion as a vehicle
      for dermal drug delivery and to develop microemulsion based gel (MBC) of
      clobetasol propionate (CP) for the effective treatment of vitiligo. D-Optimal
      mixture experimental design was adopted to optimize the amount of oil (X(1)),
      S(mix) (mixture of surfactant and cosurfactant) (X(2)) and water (X(3)) in the
      microemulsion. The formulations were assessed for globule size (nm) (Y(1)) and
      solubility of CP in microemulsion (mg/ml) (Y(2)). The microemulsion containing 3%
      oil, 45% S(mix) and 50% water was selected as the optimized batch (ME). The
      globule size and solubility of CP in ME were 18.26 nm and 36.42 mg/ml
      respectively. Transmission electron microscopy showed that ME globules were
      spherical in shape. Carbopol 934P was used to convert microemulsion containing
      drug into gel form without affecting its structure. Ex-vivo permeation studies
      showed that cumulative amount of CP permeated (Q(n)) from ME, MBC and market
      formulation (MFCP) at 8h after application were 53.6+/-2.18, 28.43+/-0.67 and
      37.73+/-0.77 MUg cm(-2) respectively. MBC showed greater retention of CP in to
      skin layers than ME and MFCP. Skin irritation studies showed MBC to be
      significantly less irritating than MFCP. Photomicrographs and scanning electron
      micrographs of skin sections treated with MBC showed significant changes in the
      skin structure, which was attributed to the interaction of microemulsion
      components with skin resulting in permeation enhancement and retention of CP into
      skin layers. It was concluded that CP loaded gel could be a promising formulation
      for effective treatment of vitiligo.

PMID- 23000678
TI  - Dodecanol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA)
      nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro.
AB  - Folate-conjugated Dol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol
      PLA-PEG-FA), was synthesized from dodecanol-poly(D,L-lactic acid), amino
      terminated poly(ethylene glycol) and folate. (1)H NMR proved the successful
      synthesis of Dol-PLA-PEG-FA. Nanoparticles (NPs) were further fabricated from Dol
      PLA-PEG-FA by using solvent evaporation-induced interfacial self-assembly method.
      The size, critical micelle concentration (CMC), cytotoxicity and selecting
      capability to cancer cells in vitro were examined for Dol-PLA-PEG-FA NPs. The
      size of NPs showed polymer concentration-dependent phenomenon in the fabrication
      process, and its polydispersity index (PDI) was very narrow. The CMC was
      determined as 1.995*10(-4) g/L in aqueous solution, which is much lower than the
      reported CMC of block copolymer self-assemble micelles. The cytotoxicity
      evaluation revealed that the obtained NPs2 are non-toxic to either breast cancer
      cell or normal endothelial cells, and the cell uptake of NPs indicated that the
      NPs demonstrated much higher selecting capability to breast cancer cells compared
      to normal fibroblast cells. The possible receptor-mediated endocytosis pathway
      mechanism was proposed. Based on the above results, it could be concluded that
      Dol-PLA-PEG-FA polymer and its nanoparticles can be potentially used as a safe
      drug carrier with strong tumor cells targeting capability for tumor chemotherapy.

PMID- 23000680
TI  - Interaction of colloidal zinc oxide nanoparticles with bovine serum albumin and
      its adsorption isotherms and kinetics.
AB  - Zinc oxide nanoparticles (ZnO NPs) are widely used in medical, industrial and
      household application owing to excellent antimicrobial property. The
      biocompatibility of nanoparticles is important for specific biomedical
      applications. The aim of this study was to stabilize and biofunctionalize ZnO NPs
      using bovine serum albumin (BSA). Here we have investigated the adsorption
      behavior of BSA onto ZnO NPs in aqueous solutions. Influence of pH on the
      adsorption of BSA onto ZnO NPs was also investigated. The study suggests that the
      electrostatic force of attraction favors the adsorption of BSA onto ZnO NPs. The
      adsorption data fitted well by Freundlich isotherm compared to Langmuir isotherm.
      The kinetics of adsorption fitted best to pseudo-second-order.

PMID- 23000679
TI  - Simple and sensitive determination of papain by resonance light-scattering with
      CdSe quantum dots.
AB  - In this contribution, a simple and sensitive method for papain detection was
      established based on the increment of the resonance light-scattering (RLS)
      intensity of mercaptoacetic acid-capped CdSe quantum dots (MAA-QDs) in aqueous
      solution. Meanwhile, the RLS characteristics and the optimal conditions were
      investigated in detail. Under the optimized conditions, the linear range of MAA
      QDs RLS intensity versus the concentration of papain was 1.0*10(-8) M to 6.0*10(
      7) M, with a correlation coefficient (R(2)) of 0.9977 and a limit of detection
      (3sigma black) of 5.1*10(-9) M. The relative standard deviation (R.S.D.) for
      1.6*10(-7) M papain was 1.0% (n=5). There was almost no interference to
      coexisting foreign substances including common ions, proteins and 20 amino acids.
      The proposed method possessed the advantages of simplicity, rapidity and
      sensitivity. Three synthetic samples were analyzed by the methodology and the
      results were satisfying. The interaction between MAA-QDs and papain was also
      investigated systematically by using visual method, transmission electron
      microscopy and time-resolved fluorescence spectra, and the results indicated that
      the main force between MAA-QDs and papain was electrostatic interaction.

PMID- 23000681
TI  - Electromagnetic nanocomposite of bacterial cellulose using magnetite nanoclusters
      and polyaniline.
AB  - Magnetic BC was biosynthesized by culturing Gluconacetobacter xylinus in a medium
      containing magnetite nanoparticle (MNP) clusters. The stable dispersion of MNP
      clusters in an aqueous solution was achieved using amphiphilic comb-like polymer
      (CLP) stabilizers to disperse the MNPs. Subsequently, a conducting polymer was
      synthesized on the magnetic BC fibers by the chemical oxidative polymerization of
      aniline. The BC fiber was fully coated with polyaniline, forming hydrogen bonds.
      The colloidal stability of the CLP-modified MNPs was characterized by optical
      imaging and UV-visible spectroscopy. The chemical structure and morphology of the
      hybrid BC layers were observed using Fourier transform infrared spectroscopy and
      scanning electron microscopy. Magnetic and conductive properties were measured to
      confirm the immobilization of MNPs and polyaniline.

PMID- 23000682
TI  - Connecting the dots in translational research.

PMID- 23000683
TI  - Inflammatory disorders: Separating good from bad.

PMID- 23000684
TI  - Autism spectrum disorders.

PMID- 23000685
TI  - Metabolic disorders: Safe cannabinoid receptor modulators in sight?

PMID- 23000687
TI  - Neurodegenerative diseases: Anti-epileptic drug shows benefit in AD mouse model.

PMID- 23000688
TI  - The interaction between body position and vibration frequency on acute response
      to whole body vibration.
AB  - PURPOSE: The present study was designed to investigate the electromyographic
      (EMG) response in leg muscles to whole-body vibration while using different body
      positions and vibration frequencies. METHODS: Twenty male sport sciences students
      voluntarily participated in this single-group, repeated-measures study in which
      EMG data from the vastus lateralis (VL) and the lateral gastrocnemius (LG) were
      collected over a total of 36 trials for each subject (4 static positions * 9
      frequencies). RESULTS: We found that vibration frequency, body position and the
      muscle stimulated had a significant effect (P-values ranged from 0.001 to 0.031)
      on the EMG response. Similarly, the muscle * frequency and position * muscle
      interactions were significant (P < 0.001). Interestingly, the frequency *
      positions interactions were not significant (P > 0.05). CONCLUSIONS: Our results
      indicate that lower frequencies of vibration (25-35 Hz) result in maximal
      activation of LG, whereas higher frequencies (45-55 Hz) elicit the highest
      responses in the VL. In addition, the position P2 (half squat position with the
      heels raised) is beneficial both for VL and LG, independently of the vibration
      frequency.

PMID- 23000686
TI  - Targeting the TGFbeta signalling pathway in disease.
AB  - Many drugs that target transforming growth factor-beta (TGFbeta) signalling have
      been developed, some of which have reached Phase III clinical trials for a number
      of disease applications. Preclinical and clinical studies indicate the utility of
      these agents in fibrosis and oncology, particularly in augmentation of existing
      cancer therapies, such as radiation and chemotherapy, as well as in tumour
      vaccines. There are also reports of specialized applications, such as the
      reduction of vascular symptoms of Marfan syndrome. Here, we consider why the
      TGFbeta signalling pathway is a drug target, the potential clinical applications
      of TGFbeta inhibition, the issues arising with anti-TGFbeta therapy and how these
      might be tackled using personalized approaches to dosing, monitoring of
      biomarkers as well as brief and/or localized drug-dosing regimens.

PMID- 23000690
TI  - Evaluation of in vivo antioxidant activity of Hericium erinaceus polysaccharides.
AB  - Hericium erinaceus polysaccharide (HEP) is a traditional Chinese medicine. In the
      present study, chemical composition and antioxidant activity of HEP was
      investigated. HPLC analysis showed that the HEP was composed of xylose (7.8%),
      ribose (2.7%), glucose (68.4%), arabinose (11.3%), galactose (2.5%) and mannose
      (5.2%). HEP was pre-administered to mice by gavage at a dose of 300 mg/kg for 15
      days. Results found that HEP preadministration resulted in a significant decline
      in blood urea nitrogen (BUN), serum creatinine (Scr) and increase in creatinine
      clearance (CrCI) levels in HEP-pretreated group compared to renal ischemia
      reperfusion (IR) group. Malondialdehyde (MDA) level significantly increased,
      whereas Level of reduced glutathione (GSH) markedly decreased in renal IR
      animals. These results indicate that IR induced renal oxidative injury damage, as
      indicated by a increase in MDA level, and decrease in GSH level as well as the
      antioxidant enzymes activity. Such effects reflect that HEP can significantly
      decrease lipid peroxidation level and increase antioxidant enzymes activities in
      experimental animals.

PMID- 23000689
TI  - Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed
      immune evasion in a mouse lymphoma model.
AB  - Lymphoma cells mobilize many mechanisms to evade the immune system. There is
      substantial evidence that CD4(+)CD25(+) regulatory T cells (Tregs) play a key
      role in the control of immune evasion. Tregs can transfer cyclic adenosine
      monophosphate (cAMP) to effector T cells, suggesting an association between
      Tregs' immune-evasion role and the intracellular cAMP pathway. In this study, we
      used A20 B-cell lymphoma mice as aggressive tumor models to investigate the
      mechanism of the depletion of Tregs by low-dose cyclophosphamide (CY, 20 mg/kg).
      The tumor-bearing mice had longer survival times and slower tumor growth rates
      following treatment with CY, but its effects were temporary. Along with the
      depletion of Tregs by low-dose CY treatment, the expression of interleukin-2 (IL
      2) in T effector cells increased, and intracellular cAMP concentrations in immune
      cells decreased. Our study demonstrates the ability of low-dose CY to reverse
      Tregs-mediated immune evasion in a mouse model. The changes in intracellular cAMP
      concentrations correlated with the upregulation of effector T cells and the
      downregulation of Tregs, indicating the close association of cAMP analogs and low
      dose CY in the immune therapy of B-cell lymphoma.

PMID- 23000692
TI  - Bring on the geeks: the case for improved modelling of capacity requirements.

PMID- 23000691
TI  - Stimulatory effect of the sulfated polysaccharide ascophyllan on the respiratory
      burst in RAW264.7 macrophages.
AB  - In this study, we investigated the bioactivity of ascophyllan in terms of
      reactive oxygen species (ROS) generation. In RAW264.7 cells, we found that
      ascophyllan induced ROS generation in a concentration-dependent manner, but with
      bell-shaped profile. Immunoblot analysis demonstrated that ascophyllan promoted
      the translocation of cytosolic subunits (p67(phox) and p47(phox)) of NADPH
      oxidase to the plasma membrane. Among mitogen activated protein (MAP) kinase
      inhibitors tested, JNK inhibitor showed the most potent inhibitory effect on
      ascophyllan-induced ROS production. Consistently, significant level of
      phosphorylated JNK MAP kinase was detected in ascophyllan-treated RAW264.7 cells.
      Our findings suggest for the first time that ascophyllan can stimulate
      macrophages to produce ROS through the activations of NADPH oxidase and JNK MAP
      kinase.

PMID- 23000693
TI  - Chest physiotherapy in paediatric patients hospitalised with community-acquired
      pneumonia: a randomised clinical trial.
AB  - BACKGROUND: Chest physiotherapy has been used to treat children hospitalised with
      pneumonia with no clear scientific evidence to support a beneficial effect. The
      objective of the current study was to evaluate the efficacy of chest
      physiotherapy as an adjuvant treatment in children hospitalised with acute
      community-acquired pneumonia. METHODS: Children (aged 1-12 years) with a clinical
      and confirmed radiological diagnosis of pneumonia sequentially admitted to a
      tertiary children hospital were eligible for this study. Participants were
      randomly selected to receive a standardised respiratory physiotherapy
      (positioning, thoracic vibration, thoracic compression, positive expiratory
      pressure, breathing exercises and forced exhalation with the glottis open or
      'huffing') three times daily in the 'intervention group' or a non-mandatory
      request to breathe deeply, expectorate the sputum and maintain a lateral body
      position once a day in the 'control group'. The primary outcomes were reduction
      in respiratory rate and severity score (respiratory rate, recession, fever,
      oxygen saturation and chest x-ray) from baseline to discharge. Secondary outcome
      was duration of hospitalisation. RESULTS: In all, 72 patients were randomly
      allocated to the intervention (n=35) or control (n=37) groups. There were no
      differences at admission on severity of pneumonia between groups. Respiratory
      rate and severity score significant decreased between admission to discharge
      within each group; however, there were no differences when comparing groups.
      Also, there was no significant difference in duration of hospitalisation between
      the control and intervention groups (6 vs 8 days, p=0.11, respectively).
      CONCLUSIONS: This clinical trial suggests that, in children hospitalised with
      moderate community-acquired pneumonia, chest physiotherapy did not have clinical
      benefits in comparison to control group.

PMID- 23000694
TI  - A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and
      gene silencing activity in vitro and in vivo.
AB  - Modification of liposomal siRNA carriers with polyethylene glycol, i.e.,
      PEGylation, is a generally accepted strategy for achieving in vivo stability and
      delivery to tumor tissue. However, PEGylation significantly inhibits both
      cellular uptake and the endosomal escape process of the carriers. In a previous
      study, we reported on the development of a multifunctional envelope-type nano
      device (MEND) for siRNA delivery and peptide-based functional devices for
      overcoming the limitations and succeeded in the efficient delivery of siRNA to
      tumors. In this study, we synthesized a pH-sensitive cationic lipid, YSK05, to
      overcome the limitations. The YSK05-MEND had a higher ability for endosomal
      escape than other MENDs containing conventional cationic lipids. The PEGylated
      YSK05-MEND induced efficient gene silencing and overcame the limitations followed
      by optimization of the lipid composition. Furthermore, the intratumoral
      administration of the YSK05-MEND resulted in a more efficient gene silencing
      compared with MENDs containing conventional cationic lipids. Collectively, these
      data confirm that YSK05 facilitates the endosomal escape of the MEND and thereby
      enhances the efficacy of siRNA delivery into cytosol and gene silencing.

PMID- 23000695
TI  - The impact of treatment density and molecular weight for fractional laser
      assisted drug delivery.
AB  - Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by
      creating narrow open micro-channels into the skin, but there is limited
      information on optimal laser settings for delivery of specific molecules. The
      objective of this study was to investigate the impact of laser treatment density
      (% of skin occupied by channels) and molecular weight (MW) for fractional CO(2)
      laser-assisted drug delivery. AFXL substantially increased intra- and
      transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to
      4300 Da (Nuclear Magnetic Resonance, p<0.01). Increasing laser density from 1 to
      20% resulted in augmented intra- and transdermal delivery (p<0.01), but densities
      higher than 1% resulted in reduced delivery per channel. Mass spectrometry
      indicated that larger molecules have greater intracutaneous retention than
      transcutaneous penetration. At 5% density, median delivery of PEGs with mean MW
      of 400, 1000, 2050 and 3350 Da were respectively 0.87, 0.31, 0.23 and 0.15 mg
      intracutaneously and 0.72, 0.20. 0.08 and 0.03 mg transcutaneously, giving a 5.8-
      and 24.0-fold higher intra- and transcutaneous delivery of PEG400 than PEG3350
      (p<0.01). This study substantiates that fractional CO(2) laser treatment allows
      uptake of small and large molecules into and through human skin, and that laser
      density can be varied to optimize intracutaneous or transcutaneous delivery.

PMID- 23000696
TI  - Prelabour rupture of membranes:  overview of diagnostic methods.
AB  - PURPOSE OF REVIEW: To evaluate diagnostic accuracy studies for rupture of the
      fetal membranes (ROM). RECENT FINDINGS: Sample sizes of recent studies are small
      and studies used different 'silver standard' definitions for ROM. Therefore,
      reported results should be interpreted with caution. Over the review period the
      focus of diagnostic studies has been on two bedside test strips: insulin-like
      growth factor-binding protein-1 (IGFBP-1) and placental alpha microglobulin-1
      (PAMG-1). Bedside tests improve the confidence of the clinician about their
      diagnosis. Compared to nitrazine or ferning test alone, IGFBP-1 and PAMG-1 are
      more accurate. However, compared to the conventional testing (combination of
      history, ferning, nitrazine, speculum and ultrasound) no statistical difference
      in accuracy was found. In-vitro PAMG-1 is shown to be superior to IGFPB-1.
      Furthermore, soluble intercellular adhesion molecule-1 and Axl receptor tyrosine
      kinase (Axl) seem to be promising new specific biomarkers for diagnosing ROM.
      SUMMARY: IGFBP-1 and PAMG-1 are the most commonly used bedside tests for
      diagnosing ROM. Both tests seem to be sensitive and specific, however, evidence
      is lacking especially in equivocal cases and comparative studies against the real
      gold standard (amnio-dye) have still not been published. Further effectiveness
      research is needed before tests can be applied in practice.

PMID- 23000697
TI  - Cardiac structure and function in normal pregnancy.
AB  - PURPOSE OF REVIEW: To review the published data on maternal cardiac adaptation to
      pregnancy. RECENT FINDINGS: Normal pregnancy is characterized by significant
      changes in the cardiovascular system. Studies on systemic arterial system and
      heart remodelling in pregnancy provide somewhat uniform results. In normal
      pregnancy, left ventricle mass, cardiac output and arterial compliance increase,
      whereas total vascular resistance decreases. In contrast, findings on left
      ventricular systolic and diastolic chamber and myocardial function are
      conflicting. SUMMARY: The major limitation of earlier studies on left ventricular
      systolic function is the use of ejection-phase indices that are dependent on
      loading conditions. Even when tissue Doppler velocity and deformation indices
      were measured, studies interpreted diastolic indices in isolation, rather than
      using validated diagnostic algorithms which account for the interdependency of
      cardiac events. Furthermore, the strong age-dependency of diastolic function
      indices was not accounted for in the majority of assessments and none of the
      studies diagnose or grade diastolic dysfunction. Future studies should aim to use
      appropriate control individuals, age-adjusted cutoff of cardiac diastolic indices
      and extended tissue Doppler velocity and deformation indices to provide objective
      information about chamber and myocardial function.

PMID- 23000698
TI  - Gestational diabetes and childhood obesity:  what is the link?
AB  - PURPOSE OF REVIEW: To review recently published studies examining the role of
      prepregnancy obesity in the relationship between gestational diabetes mellitus
      and childhood obesity. RECENT FINDINGS: Seven epidemiologic studies published
      from January 2011 to February 2012 differentiate between preexisting diabetes
      mellitus and gestational diabetes mellitus, and six of them examine the role of
      maternal obesity. In studies that account for maternal obesity as a covariate,
      the association between gestational diabetes mellitus and childhood obesity is
      attenuated significantly after adjustment for prepregnancy BMI. In the one study
      that does not adjust for maternal obesity, maternal glucose level during
      pregnancy is associated with greater offspring adiposity, independent of the
      child's diet and lifestyle. SUMMARY: This review shows a positive association
      between maternal gestational diabetes mellitus and offspring overweight and
      obesity that is attenuated significantly after adjustment for prepregnancy BMI.
      The relationship between maternal gestational diabetes mellitus and offspring
      overweight and obesity could reflect fetal programming, shared genes and/or
      shared environments, such as postnatal diet and physical activity. Maternal
      gestational hyperglycemia and subsequent fetal hyperinsulinemia may predispose
      offspring to increased adiposity, impaired glucose tolerance, hyperinsulinemia,
      and insulin resistance. Because maternal obesity is a more prevalent condition
      than gestational diabetes mellitus and strongly associated with offspring
      obesity, effective interventions addressing prepregnancy obesity need to be
      further explored as they may have a greater public health impact on childhood
      overweight and obesity than those targeting women with gestational diabetes
      mellitus.

PMID- 23000699
TI  - Modeling of non-covalent complexes of the cell-penetrating peptide CADY and its
      siRNA cargo.
AB  - CADY is a cell-penetrating peptide spontaneously making non-covalent complexes
      with Short interfering RNAs (siRNAs) in water. Neither the structure of CADY nor
      that of the complexes is resolved. We have calculated and analyzed 3D models of
      CADY and of the non-covalent CADY-siRNA complexes in order to understand their
      formation and stabilization. Data from the ab initio calculations and molecular
      dynamics support that, in agreement with the experimental data, CADY is a
      polymorphic peptide partly helical. Taking into consideration the polymorphism of
      CADY, we calculated and compared several complexes with peptide/siRNA ratios of
      up to 40. Four complexes were run by using molecular dynamics. The initial
      binding of CADYs is essentially due to the electrostatic interactions of the
      arginines with siRNA phosphates. Due to a repetitive arginine motif (XLWR(K)) in
      CADY and to the numerous phosphate moieties in the siRNA, CADYs can adopt
      multiple positions at the siRNA surface leading to numerous possibilities of
      complexes. Nevertheless, several complex properties are common: an average of
      14+/-1 CADYs is required to saturate a siRNA as compared to the 12+/-2 CADYs
      experimentally described. The 40 CADYs/siRNA that is the optimal ratio for vector
      stability always corresponds to two layers of CADYs per siRNA. When siRNA is
      covered by the first layer of CADYs, the peptides still bind despite the
      electrostatic repulsion. The peptide cage is stabilized by hydrophobic CADY-CADY
      contacts thanks to CADY polymorphism. The analysis demonstrates that the
      hydrophobicity, the presence of several positive charges and the disorder of CADY
      are mandatory to make stable the CADY-siRNA complexes.

PMID- 23000700
TI  - Time to death and the forecasting of macro-level health care expenditures: some
      further considerations.
AB  - Although the effect of time to death (TTD) on health care expenditures (HCE) has
      been investigated using individual level data, the most profound implications of
      TTD have been for the forecasting of macro-level HCE. Here we estimate the TTD
      model using macro-level data from the Netherlands consisting of mortality rates
      and age- and gender-specific per capita health expenditures for the years 1981
      2007. Forecasts for the years 2008-2020 of this macro-level TTD model were
      compared to forecasts that excluded TTD. Results revealed that the effect of TTD
      on HCE in our macro model was similar to those found in micro-econometric
      studies. As the inclusion of TTD pushed growth rate estimates from unidentified
      causes upwards, however, the two models' forecasts of HCE for the 2008-2020 were
      similar. We argue that including TTD, if modeled correctly, does not lower
      forecasts of HCE.

PMID- 23000701
TI  - RELION: implementation of a Bayesian approach to cryo-EM structure determination.
AB  - RELION, for REgularized LIkelihood OptimizatioN, is an open-source computer
      program for the refinement of macromolecular structures by single-particle
      analysis of electron cryo-microscopy (cryo-EM) data. Whereas alternative
      approaches often rely on user expertise for the tuning of parameters, RELION uses
      a Bayesian approach to infer parameters of a statistical model from the data.
      This paper describes developments that reduce the computational costs of the
      underlying maximum a posteriori (MAP) algorithm, as well as statistical
      considerations that yield new insights into the accuracy with which the relative
      orientations of individual particles may be determined. A so-called gold-standard
      Fourier shell correlation (FSC) procedure to prevent overfitting is also
      described. The resulting implementation yields high-quality reconstructions and
      reliable resolution estimates with minimal user intervention and at acceptable
      computational costs.

PMID- 23000702
TI  - A site-specific focused-ion-beam lift-out method for cryo Transmission Electron
      Microscopy.
AB  - The focused-ion-beam (FIB) is the method of choice for site-specific sample
      preparation for Transmission Electron Microscopy (TEM) in material sciences. A
      lamella can be physically lifted out from a specific region of a bulk specimen
      with submicrometer precision and thinned to electron transparency for high
      resolution imaging in the TEM. The possibility to use this tool in life sciences
      applications has been limited by the lack of lift-out capabilities at the
      cryogenic temperatures often needed for biological samples. Conventional cryo-TEM
      sample preparation is mostly based on ultramicrotomy, a procedure that is not
      site-specific and known to produce artifacts. Here we demonstrate how a cooled
      nanomanipulator and a custom-built transfer station can be used to achieve cryo
      preparation of TEM samples with the FIB, enabling high-resolution investigation
      of frozen-hydrated specimens in the TEM.

PMID- 23000703
TI  - Novel structural features of xylanase A1 from Paenibacillus sp. JDR-2.
AB  - The Gram-positive bacterium Paenibacillus sp. JDR-2 (PbJDR2) has been shown to
      have novel properties in the utilization of the abundant but chemically complex
      hemicellulosic sugar glucuronoxylan. Xylanase A1 of PbJDR2 (PbXynA1) has been
      implicated in an efficient process in which extracellular depolymerization of
      this polysaccharide is coupled to assimilation and intracellular metabolism.
      PbXynA1is a 154kDa cell wall anchored multimodular glycosyl hydrolase family 10
      (GH10) xylanase. In this work, the 38kDa catalytic module of PbXynA1 has been
      structurally characterized revealing several new features not previously observed
      in structures of GH10 xylanases. These features are thought to facilitate
      hydrolysis of highly substituted, chemically complex xylans that may be the form
      found in close proximity to the cell wall of PbJDR2, an organism shown to have a
      preference for growth on polymeric glucuronoxylan.

PMID- 23000704
TI  - Reconstitution of the Escherichia coli cell division ZipA-FtsZ complexes in
      nanodiscs as revealed by electron microscopy.
AB  - ZipA is an element of the bacterial division ring complex that provides an anchor
      to the membrane to FtsZ, a GTPase ancestor of tubulin. In vitro reconstitution
      and characterization of these interactions is challenged by the difficulty to
      integrate a physiological membrane environment. Here a single copy of the full
      length ZipA protein from Escherichia coli incorporated into phospholipid bilayer
      nanodiscs (Nd-ZipA) has been visualized using negative-staining electron
      microscopy (EM). The EM images reveal the presence of discs, mostly organized in
      two distinct populations of 11 and 13nm in diameter. The globular FtsZ-binding C
      terminal domain of ZipA (ZBD) was not visible in 3D reconstructions of Nd-ZipA or
      2D averages, suggesting that this domain is separated from the membrane by the
      large flexible domain connecting the N-terminal trans-membrane region to the ZBD.
      We tested if Nd-ZipA were appropriate models for the in vitro reconstitution of
      ZipA-FtsZ interactions. First we observed that the ZBD region of ZipA was
      accessible for the interaction with other proteins in the context of the
      nanodisc, as revealed by its recognition by specific antibodies. In addition, Nd
      ZipA attached to carbon coated EM grids, but not empty nanodiscs, were able to
      capture FtsZ filaments without inducing significant filament bundling, consistent
      with a model in which FtsZ filaments are loosely attached to the cell-membrane.
      These observations are compatible with the plastic nature of the ZipA-FtsZ
      complexes formed at the membrane, evidenced in the moderate binding affinity of
      Nd-ZipA to FtsZ oligomers and polymers recently measured.

PMID- 23000705
TI  - Unraveling the structure of membrane proteins in situ by transfer function
      corrected cryo-electron tomography.
AB  - Cryo-electron tomography in combination with subtomogram averaging allows to
      investigate the structure of protein assemblies in their natural environment in a
      close to live state. To make full use of the structural information contained in
      tomograms it is necessary to analyze the contrast transfer function (CTF) of
      projections and to restore the phases of higher spatial frequencies. CTF
      correction is however hampered by the difficulty of determining the actual
      defocus values from tilt series data, which is due to the low signal-to-noise
      ratio of electron micrographs. In this study, an extended acquisition scheme is
      introduced that enables an independent CTF determination. Two high-dose images
      are recorded along the tilt axis on both sides of each projection, which allow an
      accurate determination of the defocus values of these images. These values are
      used to calculate the CTF for each image of the tilt series. We applied this
      scheme to the mycobacterial outer membrane protein MspA reconstituted in lipid
      vesicles and tested several variants of CTF estimation in combination with
      subtomogram averaging and correction of the modulation transfer function (MTF).
      The 3D electron density map of MspA was compared with a structure previously
      determined by X-ray crystallography. We were able to demonstrate that structural
      information up to a resolution of 16.8A can be recovered using our CTF correction
      approach, whereas the uncorrected 3D map had a resolution of only 26.2A.

PMID- 23000706
TI  - Editorial: a new study design?

PMID- 23000707
TI  - Soft tissue management for dental implants: what are the most effective
      techniques? A Cochrane systematic review.
AB  - This review is based on a Cochrane systematic review entitled 'Interventions for
      replacing missing teeth: management of soft tissues for dental implants'
      published in The Cochrane Library (see http:// www.cochrane.org/ for
      information). Cochrane systematic reviews are regularly updated to include new
      research, and in response to comments and criticisms from readers. If you wish to
      comment on this review, please send your comments to the Cochrane website or to
      Marco Esposito. The Cochrane Library should be consulted for the most recent
      version of the review. The results of a Cochrane review can be interpreted
      differently, depending on people's perspectives and circumstances. Please
      consider the conclusions presented carefully. They are the opinions of the review
      authors, and are not necessarily shared by the Cochrane Collaboration. PURPOSE:
      To evaluate whether flapless procedures are beneficial for patients and which is
      the ideal flap design, whether soft tissue correction/augmentation techniques are
      beneficial for patients and which are the best techniques, whether techniques to
      increase the peri-implant keratinised mucosa are beneficial for patients and
      which are the best techniques, and which are the best suturing techniques/
      materials. MATERIALS AND METHODS: The Cochrane Oral Health Group's Trials
      Register, CENTRAL, MEDLINE and EMBASE were searched up to the 9th of June 2011
      for randomised controlled trials (RCTs) of rootform osseointegrated dental
      implants, with a follow-up of at least 6 months after function, comparing various
      techniques to handle soft tissues in relation to dental implants. Primary outcome
      measures were prosthetic failures, implant failures and biological complications.
      Screening of eligible studies, assessment of the methodological quality of the
      trials and data extraction were conducted at least in duplicate and independently
      by two or more review authors. The statistical unit was the patient and not the
      prosthesis, the procedure or the implant. RESULTS were expressed using risk
      ratios for dichotomous outcomes and mean differences for continuous outcomes with
      95% confidence intervals (CI). RESULTS: Seventeen potentially eligible RCTs were
      identified but only six trials with 138 patients in total could be included. The
      following techniques were compared in the six included studies: flapless
      placement of dental implants versus conventional flap elevation (2 trials, 56
      patients), crestal versus vestibular incisions (1 trial, 10 patients), Erbium:YAG
      laser versus flap elevation at the second-stage surgery for implant exposure (1
      trial, 20 patients), whether a connective tissue graft at implant placement could
      be effective in augmenting peri-implant tissues (1 split-mouth trial, 10
      patients), and autograft versus an animal-derived collagen matrix to increase the
      height of the keratinised mucosa (1 trial, 40 patients). On a patient rather than
      per implant basis, implants placed with a flapless technique and implant
      exposures performed with laser lead to statistically significantly less
      postoperative pain than flap elevation. Sites augmented with soft tissue
      connective grafts had better aesthetics and thicker tissues. Both palatal
      autografts or the use of a porcine-derived collagen matrix are effective in
      increasing the height of keratinised mucosa at the cost of a 0.5 mm recession of
      peri-implant soft tissues. There were no other statistically significant
      differences for any of the remaining analyses. CONCLUSIONS: There is limited weak
      evidence suggesting that flapless implant placement is feasible and has been
      shown to reduce patient postoperative discomfort in adequately selected patients,
      that augmentation at implant sites with soft tissue grafts is effective in
      increasing soft tissue thickness and improving aesthetics, and that one technique
      to increase the height of keratinised mucosa using autografts or an animal
      derived collagen matrix was able to achieve its goal but at the cost of a
      worsened aesthetic outcome (0.5 mm of recession). There is insufficient reliable
      evidence to provide recommendations on which is the ideal flap design, the best
      soft tissue augmentation technique, whether techniques to increase the width of
      keratinised/attached mucosa are beneficial to patients or not, and which are the
      best incision/suture techniques/materials. Properly designed and conducted RCTs,
      with at least 6 months of follow-up, are needed to provide reliable answers to
      these questions.

PMID- 23000708
TI  - Safety and effectiveness of maxillary early loaded titanium implants with a novel
      nanostructured calcium-incorporated surface (Xpeed): 1-year results from a pilot
      multicenter randomised controlled trial.
AB  - PURPOSE: To evaluate clinical safety and effectiveness of a novel calcium
      incorporated titanium implant (Xpeed, MegaGen Implant Co. Limited, Gyeongbuk,
      South Korea). MATERIALS AND METHODS: Sixty patients were randomised to receive
      either 1 to 6 calcium-incorporated or control titanium implants in the maxilla
      according to a parallel group design at 2 different centres. Implants were
      submerged and exposed at 3 different endpoints in equal groups of 20 patients
      each at 12, 10 and 8 weeks, respectively. Within 2 weeks, implants were
      functionally loaded with provisional or definitive prostheses. Outcome measures
      were prosthesis failures, implant failures, any complications and peri-implant
      marginal bone level changes. RESULTS: Thirty patients received 45 calcium
      incorporated implants and 30 patients received 42 control titanium implants. One
      year after loading, no drop-outs and no prosthesis or implant failures occurred.
      There were no statistically significant differences between groups for
      complications (P = 0.61; difference in proportions = -0.27; 95% CI -0.71 to 0.18)
      and mean marginal bone level changes (P = 0.64; mean difference -0.04 mm; 95% CI 
      0.22 to 0.13). CONCLUSIONS: Nanostructured calcium-incorporated titanium implants
      seem to be at least as effective and safe as conventional titanium implants.

PMID- 23000709
TI  - A within-implant comparison to evaluate the concept of platform switching: a
      randomised controlled trial.
AB  - PURPOSE: To evaluate whether platform switching could preserve marginal bone
      around implants up to 6 months after loading. MATERIALS AND METHODS: 15 patients
      were selected for a randomised controlled trial. Each patient received one
      customised wide body implant, with the external hex connection located
      eccentrically, allowing an extra 1 mm switch on one side. The hex was positioned
      at random at the mesial or distal side and the implant was loaded after 6 months
      of non-submerged healing. Patients were examined at 3, 6 and 12 months after
      surgery, during which a radiograph was taken to evaluate bone levels. At 12
      months, the mucosal thickness was measured using a perio-probe. RESULTS: All
      implants survived and the mean overall bone loss, calculated from both the
      switched and non-switched side, was 0.39 mm (SD 0.33, range 0.00-1.45), 0.85 mm
      (SD 0.59, range 0.10-2.50) and 0.80 mm (SD 0.46, 0.26-1.89) after 3, 6 and 12
      months, respectively. The bone loss continued up to 6 months but stabilised
      thereafter (P = 0.615). Significantly more bone loss was observed at the non
      switched side compared to the switched side at 3 months (0.51 mm versus 0.28 mm,
      P = 0.019), 6 months (1.05 mm versus 0.64 mm, P = 0.002) and 12 months (0.94 mm
      versus 0.66 mm, P = 0.002). The mean mucosal thickness was 4.22 mm (SD 1.45;
      range 1.50-7.00), and was not significantly different between the switched and
      non-switched sides (P = 0.882). However, using a post-hoc analysis with the mean
      thickness as a threshold, the mean bone loss was only significantly different
      between switched and non-switched sides when the mucosa was thicker than 4.22 mm
      (P = 0.036). CONCLUSIONS: The outcome of this randomised trial is in accordance
      with earlier studies suggesting that that platform switching decreases bone loss
      by 30%. Although the sample size was limited, it seems that the creation of a
      biologic width affects peri-implant bone loss to a significant extent and that
      platform switching is only effective when the mucosal thickness allows the
      establishment of a biologic width.

PMID- 23000710
TI  - Short (5 and 7 mm long) porous implants in the posterior atrophic maxilla: a 5
      year report of a prospective single-cohort study.
AB  - PURPOSE: The aim of this ongoing prospective study was to determine the 5-year
      survival rate of short porous dental implants in the posterior atrophic maxilla
      combined, when necessary, with crestal sinus floor elevation and often adding
      anorganic bovine bone. MATERIALS AND METHODS: In 87 partially edentulous
      patients, 110 short porous implants were placed and followed up for 5 years. The
      implants used were of two lengths (5 and 7 mm) and two diameters (4.1 and 5 mm)
      and were chosen according to the available crestal height and width. In 47 sites,
      osteotome sinus floor elevation was performed (in 8 cases compacting basal bone,
      in 39 adding a xenograft). The unloaded healing period was 6 months. A total of
      63 implants were restored with single crowns and 47 were splinted to the adjacent
      implants. Outcome measures were prosthesis and implant failures, any
      complications, and peri-implant marginal bone resorption. RESULTS: Five years
      after loading, no patients dropped out. Eleven implants failed: 2 implants at
      uncovering and 9 after prosthetic loading. Eleven patients (12.6%) lost 1
      implant. In 6 patients (6.9%) a prosthesis failure occurred (implants loaded with
      single crowns). One surgical complication (membrane perforation) occurred but the
      implant was normally inserted. No complications occurred during the healing
      period. In 3 patients, severe peri-implantitis occurred post loading and the
      implants had to be removed. Two abutments became loose and one crown chipped. At
      the end of the follow-up period the implant survival rate was 90%, and 93.1% with
      regard to prosthetic reconstruction. The mean peri-implant marginal bone loss was
      1.4 mm. CONCLUSIONS: The use of short porous implants showed an acceptable
      clinical outcome in the treatment of the posterior maxilla in this interim 5-year
      report. Longer follow-ups are needed to confirm these results.

PMID- 23000711
TI  - Immediate loading of four (all-on-4) post-extractive implants supporting
      mandibular cross-arch fixed prostheses: 18-month follow-up from a multicentre
      prospective cohort study.
AB  - AIM: To evaluate the outcome of immediately loaded mandibular cross-arch
      prostheses according to the 'all-on-4' concept supported by implants placed in
      fresh extraction sockets up to 18 months after loading. MATERIALS AND METHODS: In
      total, 47 patients with a mean age of 62.3 years (range 52 to 78) were
      rehabilitated with an immediately loaded fixed cross-arch prosthesis supported by
      four post-extractive implants. A total of 188 implants were inserted. Patients
      received a provisional fixed dental prosthesis with a metal framework within 48
      hours after surgery and a permanent one 6 months later. The patients were
      evaluated clinically and radiographically at implant placement and at 6-, 12- and
      18-month follow-up examinations. RESULTS: At the 18-month follow-up, no implant
      failed and all restorations were stable. Peri-implant bone levels amounted to
      0.31 +/- 0.12 mm after 6 months, 0.58 +/- 0.112 mm after 12 months and 0.7 +/-
      0.107 mm after 18 months. No significant differences in bone loss were found
      between axially placed and tilted implants at the 6-month (0.06 mm; P = 0.115),
      the 12-month (0.12 mm; P = 0.062) and the 18-month follow-up (0.08 mm; P =
      0.146). Three patients had a fracture of the provisional restoration, but all of
      the definitive prostheses remained stable throughout the study period without any
      complications. CONCLUSIONS: Within the limits of this study, it can be suggested
      that immediately loaded mandibular cross-arch fixed dental prostheses can be
      supported by four post-extractive implants, however larger and longer follow-ups
      are needed.

PMID- 23000712
TI  - Severe bleeding after sinus floor elevation using the transcrestal technique: a
      case report.
AB  - AIM: To present a rare but clinically significant complication to sinus floor
      elevation (SFE) using the transcrestal technique. MATERIALS AND METHODS:
      Transcrestal SFE with simultaneous implant placement was performed in the
      maxillary right second premolar region of a healthy 70-year-old woman with no
      history of a bleeding disorder. RESULTS: The patient reported to the emergency
      care unit a few hours after the surgery with ongoing bleeding and progressive
      swelling of especially the right side of the midface. The buccal swelling did not
      allow the patient to close her mouth and the discoloration extended to the
      sternum. A computed tomography scan showed pronounced swelling of the facial soft
      tissue and the right sinus cavity completely filled with blood. The patient was
      kept hospitalised for 3 days until regression of the swelling was attained and
      acceptable oral function was regained. CONCLUSION: Transcrestal SFE is often
      recommended to the less experienced surgeon before the lateral window technique
      due to fewer complications and lower morbidity. The present case illustrates that
      severe complications may accompany transcrestal SFE. Although rare, clinicians
      performing SFE should be aware of this potential risk.

PMID- 23000713
TI  - "On the money" - monetary and numerical judgments of currency.
AB  - Numerical and monetary judgments of currency were examined using two tasks-a
      monetary value task (which coin has a higher monetary value), and a numerical
      value task (which coin has a higher numerical value). In Experiment 1
      participants were presented with pictures of coins of the Israeli currency. The
      Israeli currency is the shekel, which is composed of 100 agorot (equivalent to a
      dollar composed of 100 cents). Higher discriminability between shekels compared
      to agorot due to importance in everyday life was reflected in faster monetary
      comparisons of shekel pairs compared to agorot pairs. Automatic processing of
      numerical value was demonstrated for monetary judgments. When presented with
      pairs composed of one coin from each monetary category, responses were faster to
      pairs that were monetary-numerical congruent (e.g., 10 shekels vs. 5 agorot)
      compared to incongruent (e.g., 5 shekels vs. 10 agorot). Numerical value
      judgments were unaffected by such congruency. There was evidence for the
      automatic activation of physical size mainly in the numerical task. A similar
      picture was obtained in Experiment 2 where instead of pictures of coins we used
      verbal descriptions of currency, demonstrating the generality of our results.

PMID- 23000714
TI  - Estimations of primary nitrogen dioxide exhaust emissions from chemiluminescence
      NOx measurements in a UK road tunnel.
AB  - NO and NO(2) measurements have been made using the chemiluminescence method from
      115 weekdays during the period 4th Jan-10th Sep 2010 in a well characterised,
      unventilated tunnel on the Leeds Inner Ring Road. Measurements are made at two
      points in the tunnel and the difference in NO and NO(2) was attributed to
      emissions from vehicles in the tunnel. These data have been used to determine the
      fraction of NOx (NO+NO(2)) as primary NO(2) (f-NO(2)) from vehicles using the
      tunnel. The average value of f-NO(2) from 7 am to 7 pm was 0.17 (-0.03)(+0.01) in
      agreement with estimations from the UK National Atmospheric Emissions Inventory
      (NAEI). However, during the day there was a reproducible increase in f-NO(2) from
      approximately 0.10 at 7 am to 0.21 at 7 pm which is not reproduced with the
      current UK vehicle fleet emissions inventories. The increase in f-NO(2) can be
      qualitatively linked to a decrease in the fraction of NOx arising from heavy
      goods vehicles and buses.

PMID- 23000715
TI  - Influence of fresh water, nutrients and DOC in two submarine-groundwater-fed
      estuaries on the west of Ireland.
AB  - Coastal fresh water sources, which discharge to the sea are expected to be
      directly influenced by climate change (e.g. increased frequency of extreme
      weather events). Sea-level rise and changes in rainfall patterns, changes in
      demand for drinking water and contamination caused by population and land use
      change, will also have an impact. Coastal waters with submarine groundwater
      discharge are of particular interest as this fresh water source is very poorly
      quantified. Two adjacent bays which host shellfish aquaculture sites along the
      coast of Co. Galway in the west of Ireland have been studied to establish the
      influence of fresh water inputs on nutrients and dissolved organic carbon (DOC)
      in each bay. Neither bay has riverine input and both are underlain by the karst
      limestone of the Burren and are susceptible to submarine groundwater discharge.
      Water and suspended matter samples were collected half hourly over 13 h tidal
      cycles over several seasons. Water samples were analysed for nutrients and DOC,
      while suspended matter was analysed for organic/inorganic content. Temperature
      and salinity measurements were recorded during each tidal station by SBE 37
      MicroCAT conductivity/temperature sensors. Long-term mooring data were used to
      track freshwater input for Kinvara and Aughinish Bays and compare it with
      rainfall data. Results show that Kinvara Bay is much more heavily influenced by
      fresh water input than Aughinish Bay, and this is a strong source of fixed
      nitrogen to Kinvara Bay. Only during flood events is there a significant input of
      inorganic nitrogen from fresh water to Aughinish Bay, such as in late November
      2009. Fresh water input does not appear to be a significant source of dissolved
      inorganic phosphate (DIP) to either bay, but is a source of DOC to both bays. C:N
      ratios of DOC/DON show a clear distinction between marine and terrestrially
      derived dissolved organic material.

PMID- 23000717
TI  - Clinical management of Crohn's disease in the elderly.
AB  - INTRODUCTION: Crohn's Disease (CD) occurs in the elderly in 5 - 25% of cases. Aim
      of our study: to define the features of clinical presentation, diagnostic tools
      and therapy of CD in old age. METHODS: In the last ten years we observed in our
      Department 47 patients affected by CD. We divided them into two groups: A (42
      patients < 65 years old) and B (5 patients >= 65 years old). A retrospective
      survey evaluated the clinical presentation, diagnosis and treatments with
      relative outcomes. RESULTS: Group A: 23/42 patients (54,76%) were operated on.
      The most important indication for surgery was intestinal obstruction (15/42 pts,
      65,2%). Small bowel resection was the most frequent surgical procedure (13/42
      pts, 56,2%). Overall, 2/23 (8,7%) of the patients developed postoperative
      complications. There was no postoperative mortality. 8 pts (34,7 %) developed
      recrudescence of CD. Group B: 3 of 5 pts were operated on. Intestinal obstruction
      was the indication for surgery in all cases (100%). Two patients underwent small
      bowel resection (66,6%) and the third patient was submitted to an ileo-colic
      resection (33,3%). There was no mortality in the aftermath of surgery. In 2/3
      operated patients (66,6%) recurrence occurred. All operations in the old patients
      were performed in urgency. CONCLUSIONS: Surgery of CD in the elderly appears in
      our experience to have the same indications and procedures as in young patients.
      The postoperative morbidity, mortality and recurrence rates are similar in two
      groups even if we observed slightly higher postoperative morbidity rates in
      elderly due to the presence of comorbidity.

PMID- 23000716
TI  - Individual dose and exposure of Italian children to ultrafine particles.
AB  - Time-activity patterns and the airborne pollutant concentrations encountered by
      children each day are an important determinant of individual exposure to airborne
      particles. This is demonstrated in this work by using hand-held devices to
      measure the real-time individual exposure of more than 100 children aged 8-11
      years to particle number concentrations and average particle diameter, as well as
      alveolar and tracheobronchial deposited surface area concentration. A GPS-logger
      and activity diaries were also used to give explanation to the measurement
      results. Children were divided in three sample groups: two groups comprised of
      urban schools (school time from 8:30 am to 1:30 pm) with lunch and dinner at
      home, and the third group of a rural school with only dinner at home. The mean
      individual exposure to particle number concentration was found to differ between
      the three groups, ranging from 6.2 * 10(4)part.cm(-3) for children attending one
      urban school to 1.6 * 10(4)part.cm(-3) for the rural school. The corresponding
      daily alveolar deposited surface area dose varied from about 1.7 * 10(3)mm(2) for
      urban schools to 6.0 * 10(2)mm(2) for the rural school. For all of the children
      monitored, the lowest particle number concentrations are found during sleeping
      time and the highest were found during eating time. With regard to alveolar
      deposited surface area dose, a child's home was the major contributor (about
      70%), with school contributing about 17% for urban schools and 27% for the rural
      school. An important contribution arises from the cooking/eating time spent at
      home, which accounted for approximately 20% of overall exposure, corresponding to
      more than 200 mm(2). These activities represent the highest dose received per
      time unit, with very high values also encountered by children with a fireplace at
      home, as well as those that spend considerable time stuck in traffic jams.

PMID- 23000718
TI  - Novel oxygen-releasing immobilized cell beads for bioremediation of BTEX
      contaminated water.
AB  - Novel oxygen-releasing bead (ORB) and oxygen-releasing immobilized cell bead
      (ORICB) were prepared. Their oxygen releasing characteristics and effect on
      degradation of benzene, toluene, ethylbenzene, and xylene (BTEX)-contaminated
      groundwater were evaluated in a column. ORB prepared by CaO(2)-encapsulated
      freezing had much better oxygen-releasing capacity (0.526 mg O(2) per ORB) than
      that by the mixing-freezing method. The encapsulated-ORB did not influence
      groundwater pH. Two BTEX degraders were utilized to prepare the ORICB. The ORICBs
      column rapidly (hydraulic retention time: 0.872 day) degraded BTEX after a 2-5
      day acclimation period. The BTEX removal increased as flow distances increased.
      At BTEX concentration of 120 mg L(-1), 67% of benzene and 81-90% of TEX were
      removed. The SEM shows that micropores existed in the ORBs and BTEX degraders
      were immobilized. The denaturing gradient gel electrophoresis profiles indicate
      that BTEX degraders were distributed throughout the column. The BTEX
      concentration of 120 mg L(-1) markedly altered the structure of the indigenous
      microbial community.

PMID- 23000719
TI  - Micro-environment characteristics and microbial communities in activated sludge
      flocs of different particle size.
AB  - Microorganisms in activated sludge flocs (ASF) play important roles in the
      wastewater treatment process. However, the interplay between micro-environmental
      variation and microbial responses within ASF is poorly understood. In this study,
      microelectrodes and molecular culture-independent techniques were applied to
      detect the internal environment, microbial composition, and distribution in flocs
      with different particle size. Results showed dissolved oxygen (DO) concentrations
      within the center of the flocs were less than at the surface, and the DO
      concentration distributions were distinct in flocs of different particle size.
      With floc particle size increasing from 100 to 250 MUm, the DO concentrations in
      the floc centers decreased 10-55%, respectively, while no distinct change was
      observed in flocs of less than 100 MUm. Similar phenomenon occurred for the
      distributions of NH(4)(+) and NO(3)(-) in flocs. Microbial structure indicated
      bacterial compositions and distributions were heterogeneous and responded to
      micro-environment variation in flocs of different particle size.

PMID- 23000720
TI  - Comparison of the energy and environmental performances of nine biomass/coal co
      firing pathways.
AB  - Life cycle energy and environmental performances of nine different biomass/coal
      co-firing pathways to power generation were compared. Agricultural residue (AR),
      forest residue (FR), and whole trees (WT) as feedstock were analyzed for direct
      (DC) and parallel co-firing (PC) in various forms (e.g., chip, bale and pellet).
      Biomass co-firing rate lies in the range of 7.53-20.45% (energy basis; rest of
      the energy comes from coal) for the co-firing pathways, depending on type of
      feedstock and densification. Net energy ratios (NER) for FR-, WT-, and AR-based
      co-firing pathways were 0.39-0.42, 0.39-0.41, and 0.37-0.38, greenhouse gas (GHG)
      emissions were 957-1004, 967-1014, and 1065-1083 kg CO(2eq)/MWh, acid rain
      precursor (ARP) emissions were 5.16-5.39, 5.18-5.41, and 5.77-5.93 kgSO(2eq)/MWh,
      and ground level ozone precursor (GOP) emissions were 1.79-1.89, 1.82-1.93, and
      1.88-1.91 kg (NO(x)+VOC)/MWh, respectively. Biomass/coal co-firing life cycle
      results evaluated in this study are relevant for any jurisdiction around the
      world.

PMID- 23000722
TI  - Estimating individual firing frequencies in a multiple spike train record.
AB  - Neuronal activity of several neurons is commonly recorded by a single electrode
      and then the individual spike trains are separated. If the separation is
      difficult or fails, then as a minimal result of the experiment, the individual
      firing rates are of interest. The proposed method solves the problem of their
      identification. This is possible under the condition that the recorded neurons
      are independent in their activities. The number of the neurons in the multi-unit
      record needs to be given (known or assumed) prior the calculation. The proposed
      method is based on the presence of the refractory period in neuronal firing,
      however, its precise value is not required. In addition to the determination of
      the individual firing rates the method can be used for an inference about the
      refractory period itself.

PMID- 23000723
TI  - Variation of stimulation intensity in transcranial magnetic stimulation with
      depth.
AB  - The quantification of stimulation intensity in transcranial magnetic stimulation
      (TMS) as a function of depth is of interest in order to adjust stimulator output
      when non-motor regions are stimulated. Currently, a linear increase of stimulator
      output to correct for depth has been suggested. This is contrary to the physical
      properties of the electric field that is induced by the stimulation coil as
      measured in vitro. For two stimulation coils, we determined the characteristics
      of their field in air. We then measured motor thresholds for the abductor
      hallucis muscle of 10 healthy subjects. Coil position, distance from the scalp,
      and orientation were controlled with a head tracking robotic system that
      corrected for head movements. In both coils an approximately exponential
      increase, rather than a linear increase, of the threshold with the scalp-coil
      distance was measured. The slope of the increase was slightly smaller than
      expected from the field characteristic, but overall in good agreement. With
      respect to the depth of the TMS target, different results were obtained from the
      threshold ratios of the coils and from the slopes of the threshold increase with
      distance. For the adjustment of stimulator output to scalp-to-cortex distances
      exponential functions with parameters motivated by physical properties of the
      coils should be used. Estimation of the target depth from the thresholds, with
      different coils, is not reliable. Our results resolve a conflict between
      physiological data and physical properties of TMS coils. They provide a more
      reliable base for depth dependent corrections for TMS stimulator output.

PMID- 23000721
TI  - The exomer cargo adaptor structure reveals a novel GTPase-binding domain.
AB  - Cargo adaptors control intracellular trafficking of transmembrane proteins by
      sorting them into membrane transport carriers. The COPI, COPII, and clathrin
      cargo adaptors are structurally well characterized, but other cargo adaptors
      remain poorly understood. Exomer is a specialized cargo adaptor that sorts
      specific proteins into trans-Golgi network (TGN)-derived vesicles in response to
      cellular signals. Exomer is recruited to the TGN by the Arf1 GTPase, a
      universally conserved trafficking regulator. Here, we report the crystal
      structure of a tetrameric exomer complex composed of two copies each of the Chs5
      and Chs6 subunits. The structure reveals the FN3 and BRCT domains of Chs5, which
      together we refer to as the FBE domain (FN3-BRCT of exomer), project from the
      exomer core complex. The overall architecture of the FBE domain is reminiscent of
      the appendage domains of other cargo adaptors, although it exhibits a distinct
      topology. In contrast to appendage domains, which bind accessory factors, we show
      that the primary role of the FBE domain is to bind Arf1 for recruitment of exomer
      to membranes.

PMID- 23000724
TI  - Repeated-dose pharmacokinetics of inhaled ciclesonide (CIC-HFA) in Japanese
      children with bronchial asthma: a phase I study.
AB  - BACKGROUND: Ciclesonide (CIC) is a highly safe, inhaled corticosteroid (ICS) that
      is converted into a pharmacologically active metabolite (des-isobutyryl
      ciclesonide); this metabolite, in turn, exerts a local anti-inflammatory effect
      on lung tissue. The present study was undertaken to analyze the pharmacokinetics
      of des-isobutyryl-ciclesonide in the serum of Japanese children with bronchial
      asthma treated by repeated doses of CIC and to compare the data thus obtained
      with those obtained for Caucasian children with bronchial asthma. METHODS: Eight
      Japanese children with bronchial asthma were treated for 7 days with CIC
      hydrofluoroalkalane (CIC-HFA) 200 MUg/day administered by a metered-dose inhaler.
      The study was designed to assess the pharmacokinetics after 7-day repeated
      administration by which the steady state can be achieved, based on the results of
      an earlier study involving healthy Japanese adult males who received 7-day
      repeated administration of CIC-HFA. Blood was sampled at multiple time points on
      Day 7 of treatment for measurement of the serum des-isobutyryl-ciclesonide level.
      RESULTS: The pharmacokinetic parameters (AUC from time zero to last observed
      concentration [AUC(t)], AUC over the dosage interval tau at steady state
      [AUC(ss)], maximum concentration [C(max)], and terminal elimination half-life
      [T(1/2)]) and the temporal changes in the serum levels of des-isobutyryl
      ciclesonide after repeated administration of CIC-HFA (200 MUg/day) in Japanese
      children with bronchial asthma differed only slightly from those in Caucasian
      children with bronchial asthma. No serious adverse events were noted during the
      study period. Additionally, no abnormalities were detected in the serum cortisol
      level, other laboratory parameters, or vital signs. CONCLUSIONS: Our results
      suggest that there is little difference in the pharmacokinetics of des-isobutyryl
      ciclesonide up on repeated administration of CIC-HFA between Japanese and
      Caucasian children with bronchial asthma. And our study suggests that CIC-HFA
      (200 MUg/day, once daily) can be administered safely for 7 days, without raising
      any safety concerns.

PMID- 23000725
TI  - A new modality using breath sound analysis to evaluate the control  level of
      asthma.
AB  - BACKGROUND: Reliable symptom assessment is essential in asthma management. We
      developed new technology for analyzing breath sounds and assessed its clinical
      usefulness for monitoring asthmatic children. METHODS: Eighty asthmatic children
      and 59 non-asthmatic children underwent breath sound analysis in an asymptomatic
      state. Their asthma control was assessed by the Asthma Control TestTM or
      Childhood ACTTM scores and divided into two groups, namely, well-controlled
      (perfect) (n = 19) and not well-controlled (not perfect) (n = 61). Breath sounds
      were recorded using two sensors, located on the right anterior chest and trachea.
      We calculated the acoustic transfer characteristics between the two points, which
      indicated the relationship between frequencies and attenuation during breath
      sound propagation. Two indices of sound parameters, the chest wall sound index
      (CWI) and the tracheal sound index (TRI), were calculated from the transfer
      characteristics and tracheal sounds. We also developed a new parameter, the
      breath sound index (BSI), on a 2-dimensional diagram of CWI and TRI and tried to
      determine whether BSI may clarify asthma control better than CWI or TRI alone.
      RESULTS: There was a significant difference in TRI and BSI between asthmatic and
      non-asthmatic children (p = 0.007, p < 0.001). There was a significant difference
      in CWI and TRI between the well-controlled and not-well-controlled groups (p <
      0.001). BSI discriminated between the two groups accurately (p < 0.001). The
      sensitivity and specificity of BSI for asthma control were 83.6% and 84.2%,
      respectively. CONCLUSIONS: Asthma control could be evaluated using a new index
      calculated from breath sound analysis.

PMID- 23000726
TI  - Effects of transdermal tulobuterol in pediatric asthma patients on  long-term
      leukotriene receptor  antagonist therapy: results of a  randomized, open-label,
      multicenter  clinical trial in Japanese children  aged 4-12 years.
AB  - BACKGROUND: Few studies have examined the efficacy or safety of a transdermal
      beta(2) agonist as add-on medication to long-term leukotriene receptor antagonist
      (LTRA) therapy in pediatric asthma patients. METHODS: In this randomized, open
      label, multicenter clinical trial, children aged 4-12 years on long-term LTRA
      therapy were treated with tulobuterol patches (1-2mg daily) or oral sustained
      release theophylline (usual dose, 4-5mg/kg daily) for 4 weeks. LTRAs were
      continued throughout the trial. Outcomes included volume of peak expiratory flow
      (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse
      events. RESULTS: Thirty-three and 31 patients were treated with tulobuterol
      patches and theophylline, respectively. % PEF measured in the morning and before
      bedtime was significantly higher at all times in the treatment period compared
      with baseline in the tulobuterol patch group (p < 0.001), and was significantly
      higher in the tulobuterol patch group compared with the theophylline group. FeNO
      was similar and unchanged from baseline in both groups. There were no drug
      related adverse events in either group. CONCLUSIONS: These results suggest that
      short-term use of a transdermal beta(2) agonist is an effective therapy for
      pediatric asthma without inducing airway inflammation in children on long-term
      LTRA therapy.

PMID- 23000727
TI  - The effect of heparin on antigen-induced mucus hypersecretion in the nasal
      epithelium of sensitized rats.
AB  - BACKGROUND: Heparin is a potential anti-inflammatory drug for allergic airway
      inflammation. To elucidate the effects of heparin on allergic inflammation, we
      examined the in vivo effects of heparin on antigen-induced mucus hypersecretion
      and infiltration of eosinophils and neutrophils in the nasal epithelium of
      sensitized rats. METHODS: We induced hypertrophic and metaplastic changes of
      goblet cells in the nasal epithelium of ovalbumin (OVA)-sensitized rats by
      intranasal challenge with OVA. The effects of intranasal instillation with low
      molecular weight heparin (LMWH; 1-1000IU/0.1ml) on mucus production and
      eosinophil/neutrophil infiltration were examined. RESULTS: Intranasal
      instillation with low-dose LMWH (1-10IU/0.1ml) at 30 minutes before OVA
      instillation stimulated OVA-induced mucus production in the nasal epithelium of
      sensitized rats, whereas treatment with 100IU/0.1ml LMWH showed no effect.
      Intranasal instillation with high-dose LMWH (1000IU/0.1ml) significantly
      inhibited OVA-induced mucus production. Intranasal instillation with LMWH (1
      1000IU/0.1ml) dose-dependently inhibited eosinophil and neutrophil infiltration
      into the rat nasal mucosa. CONCLUSIONS: These results indicate that heparin
      inhibits mucus hypersecretion and infiltration of eosinophils and neutrophils in
      allergic inflammation, though the inhibitory effect against mucus production is
      obtained in high-dose heparin. Intranasal instillation with high-dose heparin may
      provide a new therapeutic strategy for the treatment of nasal allergic
      inflammation.

PMID- 23000729
TI  - Prophylaxis of intranasally induced pollen allergy in a BALB/C mouse model using
      a potential prebiotic beta-1, 4 mannobiose.
AB  - BACKGROUND: Dietary supplementation with unique prebiotic nondigestible
      carbohydrates has been shown to suppress allergy. In the present study, the
      prophylactic efficacy of a disaccharide beta-1, 4 mannobiose (MNB) in a BALB/C
      mouse model of intranasally-induced pollen allergy was characterized. METHODS:
      Balb/c mice were pretreated with MNB orally and sensitized with pollen extract
      intraperitoneally and intranasally and challenged with histamine and crude pollen
      extract. Outcomes were measured as clinical signs, antibody isotypes, cytokine
      gene and protein expression patterns. RESULTS: The MNB-treated mice had lower
      sneezing frequency as compared to the positive control mice (P < 0.05). The low
      dose MNB-treated mice had less histamine (P < 0.05). However, the Cry j1 and Cry
      j 2-specific IgE, IgG, IgG1 and IgG2a antibody activity did not differ between
      groups (P > 0.05). The MNB-treated mice had increased IFN-gamma (P < 0.05), and
      decreased IL-4 (P < 0.05). Mice in the high dose group had increased IL-10 (P <
      0.05). However, TGF-beta and IL-17 concentration did not differ between groups (P
      > 0.05). Both total and Cry j1 and Cry j 2-specific IgA were increased in the
      high dose group. Real-time RT-PCR analysis indicated that IL-4 and IL-17 mRNA
      expression were lower in MNB-treated mice (P < 0.05). CONCLUSIONS: This work
      provides insights into using MNB as a potential prebiotic immunomodulator via
      decreased clinical signs, improved type1/type 2 balance, and IgA production, thus
      validating the potential use of MNB as a prophylactic prebiotic candidate to
      attenuate allergic response.

PMID- 23000728
TI  - Clinical significance of interleukin 33 (IL-33) in patients with eosinophilic
      pneumonia.
AB  - BACKGROUND: Interleukin 33 (IL-33) works as a functional mediator in allergic
      disease by enhancing the activity of eosinophils and inducing expression of T
      helper 2 (Th2)-associated cytokines. However, the role of IL-33 in pulmonary
      eosinophilia has not been elucidated. We investigated the levels of IL-33 in
      eosinophilic pneumonia (EP) together with associated cytokines, and discussed the
      clinical significance of IL-33 in EP. METHODS: Sera and bronchoalveolar lavage
      fluid (BALF) were obtained from 16 patients with EP, including acute eosinophilic
      pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Twelve patients with
      acute respiratory distress syndrome (ARDS) were also included for comparison. The
      concentration of IL-33 and Th2 cytokines (IL-4, IL-5, IL-13) were measured by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of serum IL
      33 was significantly higher in patients with AEP than in CEP. In CEP, only
      patients with atopic factors showed mild increase of serum IL-33. The
      concentration of BALF IL-33 was also significantly elevated in AEP, however, it
      remained quite low in CEP. Among Th2 cytokines, IL-5 was significantly increased
      in both serum and BALF in AEP, and the level of IL-5 was positively correlated
      with that of IL-33. ARDS showed no increase of serum and BALF IL-33. CONCLUSIONS:
      The remarkable increase of BALF IL-33 in AEP indicated the local production of IL
      33 in lungs. IL-33 is considered to be a local key molecule for triggering
      pulmonary eosinophilia, together with IL-5. BALF IL-33 appears to be a useful
      marker for discriminating AEP from CEP and ARDS.

PMID- 23000730
TI  - Efficacy of using the Japanese  version of the asthma control  test for determing
      the level of  asthma control in clinical settings.
AB  - BACKGROUND: The Asthma Control Test (ACT) is frequently used for the evaluation
      of asthma control in clinical care setting because it does not require the use of
      pulmonary function tests, which can be difficult for general practitioners to
      use. However, few large-scale studies have investigated the efficacy of the
      Japanese version ACT (J-ACT) in actual use during clinical care. METHODS: The aim
      of this study was to analyze the efficacy of the J-ACT in a clinical care
      setting. Using data from a 2008 questionnaire survey including the J-ACT by the
      Niigata Asthma Treatment Study Group, we compared the ACT scores of 2233 patients
      with respect to multiple parameters, including the severity by Japanese Society
      of Allergology and the attack frequency. Using the definition of asthma control
      partially referred to Global Initiative for Asthma (GINA) guidelines from the
      survey data, the accuracy screening and determination of optimal ACT cutpoints
      were performed by retrospective analysis. RESULTS: Cronbach's alpha for the J-ACT
      was 0.785. Patients with more severe asthma and more frequent asthma attacks had
      lower ACT scores than did patients with less severe, less frequent attacks. The
      optimal ACT cutpoints were 24 for the controlled asthma and 20 for the
      uncontrolled asthma. CONCLUSIONS: Our study, the first large-scale investigation
      of the efficacy of the J-ACT, determined that this evaluation tool is highly
      efficacious in establishing the level of asthma control. However, the
      determination of accurate cutpoints for the J-ACT will require more clear
      definitions of asthma control in future prospective studies.

PMID- 23000731
TI  - Management of sleep apnea in the cleft population.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea is prevalent in children with facial
      clefts. As there are increasing concerns that sleep disordered breathing and
      obstructive sleep apnea may lead to cognitive difficulties, it is imperative that
      the otolaryngologist and cleft surgeon be aware of the concerns for sleep
      disorders and implement appropriate interventions for the management. RECENT
      FINDINGS: Micrognathia associated with Robin Sequence has long been understood to
      have significant potential for sleep apnea. Positioning, nasopharyngeal airway,
      tongue-lip adhesion and mandibular distraction have been used to improve the
      breathing in this set of children. Screened by symptoms, a large proportion of
      children with clefts will have a positive sleep study. Syndromic children seem to
      be more prone to this, even though nonsyndromic children are also at risk.
      Children who have had secondary management of velopharyngeal insufficiency with
      pharyngeal flap and sphincter pharyngoplasty seem to be at greater risk of sleep
      disorder. Specific directed therapies should provide the optimum results for the
      correction including tonsillectomy with partial adenoidectomy, revision
      pharyngoplasty, maxillary advancement and continuous positive airway pressure for
      sleep. SUMMARY: Awareness of the risk of sleep disorders and the possible
      treatments in children with cleft deformities is very important for the
      otolaryngologist.

PMID- 23000732
TI  - Ultrasound imaging of the larynx and vocal folds:  recent applications and
      developments.
AB  - PURPOSE OF REVIEW: This article reviews recent clinical applications of
      ultrasound imaging in laryngeal examinations and new developments in imaging
      techniques for laryngeal tissue characterization. RECENT FINDINGS: The B-mode
      image has become a popular tool for identifying masses, lesions, and nodules at
      the vocal folds, and combining the B-scan with Doppler imaging makes it possible
      to also evaluate their functionality. The B-mode image has been used to diagnose
      lesions and paralysis in vocal folds in children, and to evaluate nerve function
      by visualizing the structure of the larynx and the movement of the bilateral
      vocal folds. Ultrasound Nakagami imaging based on the statistics of backscattered
      signals is a new parametric imaging method that complements the conventional B
      scan for tissue characterization. Nakagami imaging is a functional ultrasound
      imaging tool for visualizing the relative concentrations of collagen and elastic
      fibers, which are key factors influencing the biomechanical properties of the
      vocal folds. SUMMARY: Future clinical applications could combine conventional B
      mode and Nakagami images to allow physicians to simultaneously evaluate the
      morphology and scatterer properties of laryngeal tissues.

PMID- 23000733
TI  - Narrow band imaging in endoscopic evaluation of the larynx.
AB  - PURPOSE OF REVIEW: Narrow band imaging (NBI) is a novel endoscopic technique
      using filtered wavelengths in order to enhance the microvascular abnormalities
      associated with the preneoplastic and neoplastic changes of the mucosal lining of
      the upper aerodigestive tract. The present review is focused on the use of NBI in
      the management of patients with laryngeal cancer. RECENT FINDINGS: The larynx and
      hypopharynx represent an ideal site for NBI application because their thin,
      nonkeratinized, stratified squamous epithelium permits optimal visualization of
      the subtle neoangiogenic changes associated with precancerous and neoplastic
      diseases, including benign processes like recurrent respiratory papillomatosis.
      These abnormal vascular patterns have been recently described in great detail and
      demonstrated to be useful diagnostic tools in different settings of laryngeal
      cancer management: from preoperative diagnosis and staging to intraoperative
      evaluation of microsurgical margins and posttreatment follow-up. Particularly
      intriguing is the capacity of NBI to properly distinguish postactinic changes
      from persistent/recurrent disease. SUMMARY: From different institutions in
      several countries, NBI continues to receive confirmations of its validity as an
      ancillary diagnostic tool for endoscopic evaluation of oncologic patients. This
      also holds true for laryngeal and hypopharyngeal neoplastic diseases.

PMID- 23000734
TI  - The new age of laryngeal imaging.

PMID- 23000735
TI  - High-speed digital imaging of the larynx:  recent advances.
AB  - PURPOSE OF REVIEW: This review presents recent advances in high-speed digital
      imaging (HSDI) of the larynx including data acquisition, data analysis, and
      clinical applicability. RECENT FINDINGS: Software designed to summarize the large
      amounts of data captured with HSDI makes it possible to quantitatively analyze
      recordings from patients, improving the accuracy of the methodology. The new
      software has been used in studies of normal individuals, increasing our knowledge
      of normal vocal fold vibratory behavior. HSDI has also been used in patient
      populations and shows promise in distinguishing various laryngeal conditions that
      are difficult to distinguish with other imaging modalities. Studies of
      postoperative patients with HSDI demonstrate the return of some vibratory
      characteristics but not others, potentially leading the way to improvements in
      surgical technique. SUMMARY: Recent advances in HSDI technology have increased
      the clinical usefulness of the imaging technology and recent studies demonstrate
      the clinical applicability of HSDI. However, challenges to widespread clinical
      use of HSDI remain.

PMID- 23000736
TI  - Understanding velocardiofacial syndrome:  how recent discoveries can help you
      improve your patient outcomes.
AB  - PURPOSE OF REVIEW: Improved recognition of velocardiofacial syndrome (VCFS) has
      led to increasing awareness of VCFS by otolaryngologists. Understanding the
      developmental biologic processes affected in VCFS patients will help improve
      treatment and outcomes. Advanced application of molecular labeling techniques has
      better outlined the role of T-Box transcription factor 1 (TBX1) as the primary
      genetic anomaly leading to VCFS. TBX1 plays multiple roles during branchial,
      cardiac, and craniofacial development and increased understanding of how these
      systems are affected by TBX1 mutations will improve patient outcomes.
      Furthermore, additional modifiers of TBX1 expression have been identified that
      may explain the variability of VCFS phenotypes. The phenotypic spectrum of VCFS
      may include cardiac anomalies, velopharyngeal insufficiency, aberrant calcium
      metabolism, and immune dysfunction. Recent interest has focused on the cognitive
      and neuropsychiatric manifestations of VCFS. Improved understanding of the
      biology of VCFS associated mutations has the potential to improve therapeutic
      outcomes. RECENT FINDINGS: This article will discuss recent developmental
      biologic understanding of the role of TBX1 and genetic modifiers generating the
      phenotypic variability seen in VCFS patients. Special attention is given to
      advances in the realms of immunodeficiency, hypocalcemia, cardiac and arterial
      patterning anomalies, velopharyngeal insufficiency, as well as cognitive and
      psychiatric problems. SUMMARY: Enhanced understanding of the multiple systems
      affected by TBX1 mutations will result in improved patient outcomes and improved
      family education. Future research will lead to improved detection of potential
      targets for gene therapy and change the way physicians counsel families and treat
      patients.

PMID- 23000737
TI  - Female size constrains egg size via the influence of reproductive organ size and
      resource storage in the seed beetle Callosobruchus chinensis.
AB  - The standard egg size model predicts that a mother lays an optimal size of eggs
      in a given environment. However, there is evidence that larger females lay larger
      eggs across diverse animal taxa. This positive correlation suggests there are
      morphological constraints on egg size imposed by the size of the maternal organ
      through which eggs pass during oviposition. There is also evidence that large
      mothers that have greater capital resources produce large eggs. We tested whether
      morphological (ovipositor width) or physiological (maternal body weight as a
      measure of capital resources) mechanisms constrain egg size, using an inbred line
      of seed beetles, Callosobruchus chinensis. In addition, we tested whether having
      a wide ovipositor relative to body size is costly in terms of egg production. Egg
      width but not length increased with ovipositor width. Egg length and width
      increased with body weight. The cost of wider ovipositor was not detected. We
      conclude that females adjust egg size depending on capital resource level under
      the morphological constraint.

PMID- 23000738
TI  - Molecular characterization and gene expression of juvenile hormone binding
      protein in the bamboo borer, Omphisa fuscidentalis.
AB  - Juvenile hormone (JH) plays an important role in many physiological processes in
      insect development, diapause and reproduction. An appropriate JH titer in
      hemolymph is essential for normal development in insects. Information concerning
      its carrier partner protein, juvenile hormone binding protein (JHBP), provides an
      alternative approach to understanding how JH regulates metamorphosis. In this
      study, we cloned and sequenced the Omphisa juvenile hormone binding protein
      (OfJHBP). The full-length OfJHBP cDNA sequence is comprised of 849 nucleotides
      with an open reading frame of 726bp encoding 242 amino acids. The molecular mass
      of the protein was estimated to be 26.94kDa. The deduced protein sequence of
      OfJHBP showed moderate homology with the lepidopteran, Heliothis virescens JHBP
      (52% amino acid identity) and lower homology with the Bombyx mori JHBP (45%) and
      the Manduca sexta JHBP (44%). The OfJHBP was expressed mainly in the fat body.
      OfJHBP transcripts in the fat body was moderately high during 3rd, 4th and 5th
      instars, then rapidly increased, reaching a peak during early diapause. The
      expression remained high in mid-diapause, then decreased in late-diapause until
      the pupal stage. Both juvenile hormone analog (JHA), methoprene, 20
      hydroxyecdysone (20E) exhibited a similar stimulatory pattern in OfJHBP
      expression of diapausing larvae. OfJHBP mRNA levels gradually increased and
      showed a peak of gene expression on the penultimate, then declined to low levels
      in the pupal stage. For in vitro gene expression, both of JHA and 20E induced
      OfJHBP mRNA expression in fat body. Fat body maintenance in vitro in the presence
      of 0.1MUg/50MUl JHA induced OfJHBP mRNA expression to high levels within the
      first 30min whereas 0.1MUg/50MUl 20E induced gene expression at 120min. To study
      the synergistic effect of these two hormones, fat body was incubated in vitro
      with 0.1MUg/50MUl JHA or 0.1MUg/50MUl 20E or a combination of both hormone for
      30min. Induction of OfJHBP expression by JHA and 20E was significantly greater
      than that of either hormone alone. These results should contribute to our
      understanding of how JHBP and JH regulate the termination of larval diapause in
      the bamboo borer.

PMID- 23000739
TI  - Hyperactive antifreeze proteins from longhorn beetles: some structural insights.
AB  - This study reports on structural characteristics of hyperactive antifreeze
      proteins (AFPs) from two species of longhorn beetles. In Rhagium mordax, eight
      unique mRNAs coding for five different mature AFPs were identified from cold
      hardy individuals. These AFPs are apparently homologues to a previously
      characterized AFP from the closely related species Rhagium inquisitor, and
      consist of six identifiable repeats of a putative ice binding motif TxTxTxT
      spaced irregularly apart by segments varying in length from 13 to 20 residues.
      Circular dichroism spectra show that the AFPs from both species have a high
      content of beta-sheet and low levels of alpha-helix and random coil. Theoretical
      predictions of residue-specific secondary structure locate these beta-sheets
      within the putative ice-binding motifs and the central parts of the segments
      separating them, consistent with an overall beta-helical structure with the ice
      binding motifs stacked in a beta-sheet on one side of the coil. Molecular
      dynamics models based on these findings show that these AFPs would be
      energetically stable in a beta-helical conformation.

PMID- 23000740
TI  - Differences in microRNAs and their expressions between foraging and dancing honey
      bees, Apis mellifera L.
AB  - Many studies have established that microRNAs (miRNAs) regulate gene expression in
      various biological processes in mammals and insects including honey bees. Dancing
      behavior is a form of communication unique to honey bees. However, it remains
      unclear which miRNAs regulate the dancing behavior in honey bees, and how. In the
      present study, total small RNAs (sRNAs) in Apis mellifera foragers and dancers
      were extracted and analyzed by a Solexa Sequencer to determine differentially
      expressed miRNAs. A small percentage (12.62%) of the unique sRNAs (the number of
      sequence types) were shared between foragers and dancers, but their expression
      accounted for 92.92% of the total sRNAs (the number of all sequence reads), and
      the length of them centered around 22nt. Out of 58 previously identified miRNAs,
      54 were present in both foragers and dancers and most of them were down-regulated
      in dancers. The fold-changes of ame-miR-34, ame-miR-210, ame-miR-278 and ame-miR
      282 were higher than 2. 86 and 104 novel miRNAs were detected in foragers and
      dancers, respectively. Furthermore, two known miRNAs (ame-miR-278 and ame-miR
      282) were confirmed, by qPCR, to have lower expressions in dancers. The target
      genes of ame-miR-278 and ame-miR-282 were associated with kinase, neural
      function, synaptotagmin and energy. These results indicate that miRNAs are
      substantially different between the foraging and dancing stages, and suggest that
      miRNAs might play important roles in regulating dancing behaviors in honey bees.

PMID- 23000741
TI  - Determination of unbound fraction of imatinib and N-desmethyl imatinib,
      validation of an UPLC-MS/MS assay and ultrafiltration method.
AB  - Imatinib is a small-molecule tyrosine kinase inhibitor with large inter
      individual but low intra-individual pharmacokinetic variability with consistent
      concentration-efficacy and concentration-toxicity relationships. For these
      reasons imatinib therapeutic drug monitoring is based on total plasma
      concentrations. However, since a significant impact of unbound imatinib
      concentrations on clinical response and/or toxicity evaluation has been
      suggested, the quantification of free fraction of imatinib and its active
      metabolite are of interest for therapeutic monitoring. Hence a reliable method
      for both separation and assay of the free fraction is needed. Using plasma
      samples spiked with imatinib (from 1000 to 7500 ng/mL) and its metabolite (from
      1000 to 2500 ng/mL), an ultrafiltration procedure and an UPLC assay which give
      reproductive values for unbound fractions of imatinib (mean 3.0+/-1.0%) and
      metabolite N-desmethyl imatinib (3.6+/-1.8%) have been developed. The validation
      of the analytical UPLC-MS/MS method associated to ultrafiltration for
      quantification of imatinib and N-desmethyl imatinib was reported. The LOQ was set
      at 10 ng/mL for imatinib and 20 ng/mL for N-desmethyl imatinib, intraday CV (%)
      ranged from 2.7 to 4.8% for imatinib and from 5.4 to 12.4% for N-desmethyl
      imatinib and interday CV (%) ranged from 5.6 to 6.5% for imatinib and from 5.4 to
      16.1% for N-desmethyl imatinib. Methodological modifications were attempted to
      overcome non specific binding (NSB) on the ultrafiltration device. Two types of
      devices previously used for unbound determination of drugs were tested. Our
      results clearly showed that the methodology and the features of devices used for
      ultrafiltration could totally compromise the determination of unbound
      concentrations of a drug.

PMID- 23000743
TI  - Perspectives on the interface of drug delivery and tissue engineering.
AB  - Controlled drug delivery of bioactive molecules continues to be an essential
      component of engineering strategies for tissue defect repair. This article
      surveys the current challenges associated with trying to regenerate complex
      tissues utilizing drug delivery and gives perspectives on the development of
      translational tissue engineering therapies which promote spatiotemporal cell
      signaling cascades to maximize the rate and quality of repair.

PMID- 23000742
TI  - Separation of fluorescently labeled phosphoinositides and sphingolipids by
      capillary electrophoresis.
AB  - Phosphoinositides (PIs) and sphingolipids regulate many aspects of cell behavior
      and are often involved in disease processes such as oncogenesis. Capillary
      electrophoresis with laser induced fluorescence detection (CE-LIF) is emerging as
      an important tool for enzymatic assays of the metabolism of these lipids,
      particularly in cell-based formats. Previous separations of phosphoinositide
      lipids by CE required a complex buffer with polymer additives which had the
      disadvantages of high cost and/or short shelf life. Further a simultaneous
      separation of these classes of lipids has not been demonstrated in a robust
      buffer system. In the current work, a simple separation buffer based on
      NaH(2)PO(4) and 1-propanol was optimized to separate two sphingolipids and
      multiple phosphoinositides by CE. The NaH(2)PO(4) concentration, pH, 1-propanol
      fraction, and a surfactant additive to the buffer were individually optimized to
      achieve simultaneous separation of the sphingolipids and phosphoinositides.
      Fluorescein-labeled sphingosine (SFL) and sphingosine 1-phosphate (S1PFL),
      fluorescein-labeled phosphatidyl-inositol 4,5-bisphosphate (PIP2) and
      phosphatidyl-inositol 3,4,5-trisphosphate (PIP3), and bodipy-fluorescein (BFL)
      labeled PIP2 and PIP3 were separated pairwise and in combination to demonstrate
      the generalizability of the method. Theoretical plate numbers achieved were as
      high as 2*10(5) in separating fluorophore-labeled PIP2 and PIP3. Detection limits
      for the 6 analytes were in the range of 10(-18)-10(-20)mol. The method also
      showed high reproducibility, as the relative standard deviation of the normalized
      migration time for each analyte in the simultaneous separation of all 6 compounds
      was less than 1%. The separation of a mixture composed of diacylglycerol (DAG)
      and multiple phosphoinositides was also demonstrated. As a final test,
      fluorescent lipid metabolites formed within cells loaded with BFLPIP2 were
      separated from a cell lysate as well as a single cell. This simple and robust
      separation method for SFL and S1PFL and various metabolites of phosphoinositide
      related signal transduction is expected to enable improved enzymatic assays for
      biological and clinical applications.

PMID- 23000744
TI  - Polymeric microdevices for transdermal and subcutaneous drug delivery.
AB  - Low cost manufacturing of polymeric microdevices for transdermal and subcutaneous
      drug delivery is slated to have a major impact on next generation devices for
      administration of biopharmaceuticals and other emerging new formulations. These
      devices range in complexity from simple microneedle arrays to more complicated
      systems incorporating micropumps, micro-reservoirs, on-board sensors, and
      electronic intelligence. In this paper, we review devices currently in the market
      and those in the earlier stages of research and development. We also present two
      examples of the research in our laboratory towards using phase change liquids in
      polymeric structures to create disposable micropumps and the development of an
      elastomeric reservoir for MEMS-based transdermal drug delivery systems.

PMID- 23000746
TI  - Microbial Community-Level Physiological Profiles (CLPP) and herbicide
      mineralization potential in groundwater affected by agricultural land use.
AB  - Diffuse groundwater pollution from agricultural land use may impact the microbial
      groundwater community, which was investigated as Community-Level Physiological
      Profiles (CLPP) using EcoPlateTM. Water was sampled from seven piezometers and a
      spring in a small agricultural catchment with diffuse herbicide and nitrate
      pollution. Based on the Shannon-Wiener and Simpson's diversity indices the
      diversity in the microbial communities was high. The response from the
      EcoPlatesTM showed which substrates support groundwater bacteria, and all 31
      carbon sources were utilized by organisms from at least one water sample.
      However, only nine carbon sources were utilized by all water samples: d-Mannitol,
      N-acetyl-d-glucosamine, putrescine, d-galacturonic acid, itaconic acid, 4-hydroxy
      benzoic acid, tween 40, tween 80, and l-asparagine. In all water samples the
      microorganisms preferred d-mannitol, d-galacturonic acid, tween 40, and 4-hydroxy
      benzoic acid as substrates, whereas none preferred 2-hydroxy benzoic acid, alpha
      d-lactose, d,l-alpha-glycerol phosphate, alpha-ketobutyric acid, l-threonine and
      glycyl-l-glutamic acid. Principal Component Analysis of the CLPP's clustered the
      most agriculturally affected groundwater samples, indicating that the
      agricultural land use affects the groundwater microbial communities. Furthermore,
      the ability to mineralize atrazine and isoproturon, which have been used in the
      catchment, was also associated with this cluster.

PMID- 23000745
TI  - Quantum dots as a platform for nanoparticle drug delivery vehicle design.
AB  - Nanoparticle-based drug delivery (NDD) has emerged as a promising approach to
      improving upon the efficacy of existing drugs and enabling the development of new
      therapies. Proof-of-concept studies have demonstrated the potential for NDD
      systems to simultaneously achieve reduced drug toxicity, improved bio
      availability, increased circulation times, controlled drug release, and
      targeting. However, clinical translation of NDD vehicles with the goal of
      treating particularly challenging diseases, such as cancer, will require a
      thorough understanding of how nanoparticle properties influence their fate in
      biological systems, especially in vivo. Consequently, a model system for
      systematic evaluation of all stages of NDD with high sensitivity, high
      resolution, and low cost is highly desirable. In theory, this system should
      maintain the properties and behavior of the original NDD vehicle, while providing
      mechanisms for monitoring intracellular and systemic nanocarrier distribution,
      degradation, drug release, and clearance. For such a model system, quantum dots
      (QDots) offer great potential. QDots feature small size and versatile surface
      chemistry, allowing their incorporation within virtually any NDD vehicle with
      minimal effect on overall characteristics, and offer superb optical properties
      for real-time monitoring of NDD vehicle transport and drug release at both
      cellular and systemic levels. Though the direct use of QDots for drug delivery
      remains questionable due to their potential long-term toxicity, the QDot core can
      be easily replaced with other organic drug carriers or more biocompatible
      inorganic contrast agents (such as gold and magnetic nanoparticles) by their
      similar size and surface properties, facilitating translation of well
      characterized NDD vehicles to the clinic, maintaining NDD imaging capabilities,
      and potentially providing additional therapeutic functionalities such as
      photothermal therapy and magneto-transfection. In this review we outline unique
      features that make QDots an ideal platform for nanocarrier design and discuss how
      this model has been applied to study NDD vehicle behavior for diverse drug
      delivery applications.

PMID- 23000747
TI  - A novel PET index, 18F-FDG-11C-methionine uptake decoupling score, reflects
      glioma cell infiltration.
AB  - The linear correlation between (11)C-methionine PET and tumor cell density is not
      well conserved at the tumor border in glioma. A novel imaging analysis method,
      voxelwise (18)F-FDG-(11)C-methionine PET decoupling analysis (decoupling score),
      was evaluated to determine whether it could be used to quantitatively assess
      glioma cell infiltration in MRI-nonenhancing T2 hyperintense lesions. METHODS:
      Data collection was performed in a prospective fashion. Fifty-four MRI
      nonenhancing T2 hyperintense specimens were stereotactically obtained from 23
      glioma patients by intraoperative navigation guidance. The decoupling score and
      tumor-to-normal tissue (T/N) ratio of (11)C-methionine PET were calculated at
      each location. Correlations between the tumor cell density at these lesions,
      decoupling score, and T/N ratio of (11)C-methionine PET were then evaluated.
      RESULTS: Both the decoupling score and the T/N ratio showed a linear correlation
      with tumor cell density at these specimens (R(2) = 0.52 and 0.53, respectively).
      Use of the decoupling score (cutoff = 3.0) allowed the detection of specimens
      with a tumor cell density of more than 1,000/mm(2), with a sensitivity and
      specificity of 93.5% and 87.5%, respectively, whereas conventional (11)C
      methionine PET (cutoff = 1.2 in T/N ratio) was able to detect with a sensitivity
      and specificity of 87.0% and 87.5%, respectively. Reconstructed images
      (decoupling map) using the decoupling score enabled the visualization of glioma
      lesions that were difficult to visualize by (11)C-methionine PET alone.
      CONCLUSION: The decoupling score showed better performance in detecting glioma
      cell infiltration than (11)C-methionine uptake alone, thus suggesting that (18)F
      FDG-(11)C-methionine uptake decoupling analysis is a powerful imaging modality
      for assessing glioma invasion.

PMID- 23000748
TI  - 11C-hydroxytryptophan uptake and metabolism in endocrine and exocrine pancreas.
AB  - Determination of the residual beta-cell mass using noninvasive tools might help
      to follow up the efficacy of new treatments in both type 1 (insulin-dependent)
      and type 2 (non-insulin-dependent) diabetes mellitus, including islet
      transplantation. beta-cells are neuroendocrine cells that can take up and
      metabolize the serotonin precursor 5-hydroxytryptophan. The serotonin pathway may
      therefore be an attractive target for the development of an imaging tracer for
      residual beta-cell mass. The aim of this study was to evaluate the uptake
      mechanism and the retention of the PET tracer (11)C-hydroxytryptophan in
      endocrine and exocrine pancreas in vitro and in vivo. METHODS: The exocrine human
      pancreas carcinoma cell line (PANC-1) and the endocrine human insulinoma cell
      line (CM) were applied for in vitro (11)C-hydroxytryptophan accumulation/efflux
      experiments and blocking studies using inhibitors of key enzymes and transporters
      involved in the serotonin pathway. Animal experiments were performed on normal
      Wistar rats and on rats pretreated with the monoamine oxidase (MAO) inhibitor
      clorgyline. After intravenous injection of (11)C-hydroxytryptophan, a 60-min
      dynamic PET scan was acquired followed by an ex vivo biodistribution study.
      Autoradiography and hematoxylin-eosin staining were performed on the dissected
      pancreas to localize the radioactivity within the pancreatic tissue. RESULTS:
      (11)C-hydroxytryptophan accumulated rapidly in both endocrine CM cells and
      exocrine PANC-1 cells. In the exocrine cells, a rapid efflux of radioactivity was
      observed, whereas most radioactivity remained trapped in the endocrine cells. PET
      images showed clear accumulation of (11)C-hydroxytryptophan in the pancreas in
      both animal groups, but with a significant 3-fold higher retention of the
      radiopharmaceutical in clorgyline-treated animals. Ex vivo biodistribution
      studies confirmed the results obtained by PET. Autoradiographs did not
      discriminate between the exocrine and endocrine pancreas in control animals,
      whereas autoradiographs showed intense radioactive spots colocalized with the
      islets of Langerhans in clorgyline-treated animals. CONCLUSION: (11)C
      hydroxytryptophan is trapped in beta-cells but not in exocrine pancreatic cells.
      beta-cell selectivity can be strongly enhanced by inhibition of MAO-A. This
      observation offers perspectives for the development of a more selective PET
      tracer for beta-cell mass, based on an (11)C-hydroxytryptophan derivative with
      increased resistance toward degradation by MAO-A.

PMID- 23000749
TI  - Molecular characterization and expression of a novel big defensin (Sb-BDef1) from
      ark shell, Scapharca broughtonii.
AB  - Big defensins, endogenous cysteine-rich antimicrobial peptides (AMPs) with
      antimicrobial activity and immunomodulatory property, play crucial roles in host
      defense against various microbial pathogens. A novel big defensin (Sb-BDef1) of
      ark shell Scapharca broughtonii was identified by expressed sequence tag (EST)
      and RACE techniques. The Sb-BDef1 cDNA contained an open reading frame (ORF) of
      336-bp encoding a polypeptide of 111 amino acids with a putative signal peptide
      of 21 amino acid residues, followed by a putative propeptide of 11 residues and a
      putative mature peptide of 79 residues. The mature peptide shared the common
      features of big defensins, including a high hydrophobic residues region (59%) in
      the N-terminus, a defensin domain in the C-terminus, which perfectly corresponds
      to the six conserved disulfide-bonded cysteine residues involved in the formation
      of the internal disulfide bridges (C1-C5, C2-C4 and C3-C6) in all big defensins
      from mollusk, horseshoe crab and amphioxus. Quantitative real-time PCR analysis
      revealed that the expression of Sb-BDef1 transcript was detected in all the
      tissues examined from normal ark shells, and the temporal expression of Sb-BDef1
      mRNA was remarkably up-regulated at 8, 16 h in hemocytes, and at 16, 24 h in
      hepatopancreas after Vibrio anguillarum-challenge, respectively. These results
      suggested that Sb-BDef1 was a constitutive and inducible acute-phase protein and
      should be involved in immune response of Gram-negative microbial infection in ark
      shell S. broughtonii.

PMID- 23000750
TI  - GFP co-expression reduces the A33R gene expression driven by a fowlpox vector in
      replication permissive and non-permissive cell lines.
AB  - The development of an effective prophylactic vaccine is still necessary to
      improve the safety of the conventional although-discontinued smallpox vaccine,
      and to protect from the threat of deliberate release of variola virus. This need
      also arises from the number of new cases of animal orthopoxvirus infections each
      year, and to reduce the risk to animal handlers. Fowlpox (FP) recombinants only
      replicate in avian species and have been developed against human infectious
      diseases, as they can elicit an effective immune response, are not cross-reactive
      immunologically with vaccinia, and represent safer and more promising immunogens
      for immunocompromised individuals. The aim of this study was the characterisation
      of two new fowlpox recombinants expressing the A33R vaccinia virus gene either
      alone (FP(A33R)) or with the green fluorescent protein (FP(A33R-GFP)) to verify
      whether GFP can affect the expression of the transgene. The results show that
      both FP(A33R) and FP(A33R-GFP) can express A33R correctly, but A33R mRNA and
      protein synthesis are higher by FP(A33R) than by FP(A33R-GFP). Therefore, GFP co
      expression does not prevent, but can reduce the level of a vaccine protein, and
      may affect the protective efficacy of the immune response.

PMID- 23000751
TI  - Detection of neutralizing antibodies against Bluetongue virus serotype 8 by an
      optimized plasma neutralization test.
AB  - The neutralization test is used commonly for quantifying neutralizing antibodies
      and for distinguishing among different virus serotypes (serotyping). Due to the
      co-circulation of multiple serotypes of Bluetongue virus (BTV), the
      neutralization test has become an important surveillance method in Europe.
      However, the existence of different protocols makes test standardization and
      interpretation of results difficult. The current paper describes the development
      of a neutralization test using plasma and addresses the factors critical for
      detection of neutralizing antibodies against BTV serotype 8 (BTV-8), such as
      virus propagation, stability of virus infectivity and origin of the BTV-8 strain.
      The results indicated that animals exposed to the Northern European BTV-8 strain
      developed low neutralizing antibody titers, particularly after vaccination and
      experimental infection. Although clearly ELISA-positive, these samples often
      yielded false negative results when tested by the neutralization test using the
      OIE recommended virus concentration of 100 TCID50/50 MUl. The sensitivity of the
      neutralization test could be improved significantly with retained specificity by
      using a reduced TCID50 and the homologous European BTV-8 strain instead of the
      South African reference strain.

PMID- 23000752
TI  - The development of a multiplex real-time PCR for the detection of herpes simplex
      virus 1 and 2, varizella zoster virus, adenovirus and Chlamydia trachomatis from
      eye swabs.
AB  - Infectious conjunctivitis can be difficult to distinguish clinically due to the
      considerable overlap in clinical presentation so clinical diagnosis of
      conjunctivitis is often insufficient. It is therefore necessary to have a rapid
      diagnostic test that differentiates between the different causes of infectious
      conjunctivitis. Screening clinical samples by sample type/syndrome based
      multiplex real time PCR would allow for rapid detection of a variety of pathogens
      simultaneously, which will in turn aid in the treatment and clinical management
      of the patient. A multiplex real-time PCR assay for rapid and simultaneous
      detection of HSV 1 and 2, VZV, adenovirus and Chlamydia trachomatis (C.
      trachomatis) from eye swabs was developed and evaluated. The multiplex assay was
      shown to be sensitive, specific and robust. Reductions in sample turn around
      times have been achieved by reducing the amount of separate tests needed to be
      carried out.

PMID- 23000753
TI  - Development and application of an indirect ELISA for detection of antibodies
      against avian hepatitis E virus.
AB  - An indirect enzyme-linked immunosorbent assay (iELISA) that could detect
      immunoglobulin G antibodies against avian hepatitis E virus (HEV) was developed.
      This assay employs a truncated C-terminal 268-amino acid recombinant ORF2 protein
      from an avian HEV genotype 3 strain isolated in China (CaHEV) as the coating
      antigen. The antigen concentration and serum dilution were optimized using a
      checkerboard titration. A cut-off value of 0.368 at OD(450nm) was determined by
      testing 120 positive and 200 negative chicken sera for avian HEV antibodies using
      the two-graph receiver operating characteristic (TG-ROC) analysis. This iELISA
      has a sensitivity of 96.1% and a specificity of 95.8%. The overall agreement
      between the iELISA and a corresponding Western blot was 97%. The iELISA was used
      to evaluate the seroprevalence of avian HEV in poultry farms in the Shandong
      province. The avian HEV seropositive rate of 35.9% was determined by testing 1871
      serum samples that were collected from 10 chicken flocks ranged from 10 to 60
      weeks of age. The iELISA that was developed in this study can be used for
      detection of immunoglobulin G antibodies against avian HEV.

PMID- 23000754
TI  - Deleterious effects of mitochondrial ROS generated by KillerRed photodynamic
      action in human cell lines and C. elegans.
AB  - KillerRed, a red fluorescent protein, is a photosensitizer that efficiently
      generates reactive oxygen species (ROS) when irradiated with green light. Because
      KillerRed is genetically encoded, it can be expressed in a spatially and
      temporally regulated manner under control of a chosen promoter and thus is a
      powerful tool for studying the downstream cellular effects of ROS. However,
      information is still limited about the effects of KillerRed-mediated production
      of ROS inside the mitochondria (mtROS). Therefore, we investigated whether mtROS
      generated by KillerRed could trigger mitochondrial damage and cell death by
      generating human cell lines (HEK293T and HeLa cells) that stably expressed
      mitochondria-targeting KillerRed (mtKillerRed). We found that mtROS generated by
      mtKillerRed caused depolarization of the mitochondrial membrane and morphological
      changes, which were partly due to the mitochondrial permeability transition
      (MPT), as well as inducing both caspase-dependent cell death (apoptosis) and
      caspase-independent cell death. In order to study the pathological processes
      initiated by mtROS in animals, transgenic Caenorhabditis elegans expressing
      mtKillerRed in muscle tissue were generated. Transgenic larvae showed
      developmental delay following light irradiation, suggesting that mtROS influenced
      the development of C. elegans larvae. In conclusion, our studies demonstrated
      that the photosensitizer KillerRed is effective at inducing oxidative damage in
      the mitochondria, and indicated that our experimental systems may be useful for
      studying the downstream cellular effects of mtROS.

PMID- 23000755
TI  - The photocytotoxicity of different lights on mammalian cells in interior lighting
      system.
AB  - In the present paper, two light sources commonly used in interior lighting
      system: incandescent light and light emitting diode (LED) were chosen to evaluate
      their influences on three kinds of mammalian cells, together with UVA and UVB,
      and the mechanism of the photocytotoxicity was investigated in terms of
      intracellular ROS production, lipid peroxidation, SOD activity and GSH level
      assays. The results showed that LED and incandescent light both had some
      photocytotoxicities. In the interior lighting condition (100lx-250lx), the
      cytotoxicities of LED and incandescent lamp on RF/6A cells (rhesus retinal
      pigment epithelium cell line) were stronger than that on two fibroblast cell
      lines, while the cytotoxicity of UVA and UVB on HS68 cells (fibroblast cell line)
      was highest in the tests. The mechanism analysis revealed that the
      photocytotoxicities of LED and incandescent lamp were both caused by cell lipid
      peroxidation. LED and incandescent light could promote the production of ROS,
      raise lipid peroxidation level and lower the activity of the antioxidant key
      enzymes in mammalian cells, and finally cause a number of cells death. However,
      the negative function of LED was significantly smaller than incandescent light
      and ultraviolet in daily interior lighting condition. And the significantly lower
      photocytotoxicity of LED might be due to the less existence of ultraviolet.
      Therefore, LED is an efficient and relative safe light source in interior
      lighting system, which should be widely used instead of traditional light source.

PMID- 23000756
TI  - Innate immunity: Multitasking NET makers.

PMID- 23000757
TI  - [Genetic polymorphism of 19 STR loci in Xinjiang Barkol Kazakh population].
AB  - OBJECTIVE: To investigate 19 short tandem repeat (STR) loci in Chinese Kazakh
      population in Barkol County with GoldeneyeTM20A multiplex amplification system.
      METHODS: DNA samples were screened from 81 unrelated individuals. The 19 loci
      were D8S1179, D21S11, CSF1PO, D3S1358, D7S820, TH01, D13S317, D2S1338, D18S51,
      D16S539, TPOX, vWA, D19S433, D5S818, PentaD, PentaE, D6S1043, D12S391 and FGA.
      The PCR products were analyzed and genotyped by ABI3130XL sequencer. RESULTS:
      These loci were highly polymorphic. The combined power of discrimination was
      0.999999999 and the combined paternity of exclusion was 0.999998914. CONCLUSION:
      GoldeneyeTM20A multiplex amplification system is very useful in forensic case
      investigation for Barkol Kazakh population.

PMID- 23000758
TI  - [Role of Wnt5a and LMP1 in the nasopharyngeal carcinogenesis by high-throughput
      tissue microarray technology].
AB  - OBJECTIVE: To investigate the molecular mechanism of Wnt5a and Epstein-Barr virus
      latent membrane protein 1 (LMP1) aberrant expression in the nasopharyngeal
      carcinogenesis and to estimate if it can act as a molecular marker for
      nasopharyngeal cancer (NPC). METHODS: Immunohistochemistry combined with
      previously made tissue microarrays were used to study the expression of Wnt5a and
      LMP1 in the nasopharyngeal carcinogenesis tissues. We investigated the role of
      over expression of Wnt5a and LMP1 in the development and progression of NPC and
      their relation with the clinicopathological features of NPC and whether they
      could act as molecular markers in benign and malignant NPC. RESULTS: The positive
      percentage of Wnt5a and LMP1 protein expression in the NPC was significantly
      increased as compared with that in atypically hyperplastic nasopharyngeal
      epithelium, hyperplastic nasopharyngeal epithelium and histologically normal
      nasopharyngeal epithelium (P<0.05, P<0.01, and P<0.01). Wnt5a and LMP1 proteins
      were significantly higher in atypically hyperplastic nasopharyngeal epithelium
      than those in the hyperplastic nasopharyngeal epithelium and normal
      nasopharyngeal epithelium (P<0.05 and P<0.01). The positive expression of Wnt5a
      and LMP1 proteins in clinical T3 and T4 staged NPC was higher than that in
      clinical T1 and T2 staged NPC (P<0.01 and P<0.05). The positive expression of
      Wnt5a protein in the NPC with lymph node metastasis was higher than that in the
      NPC without lymph node metastasis (P<0.01). The positive percentage of LMP1
      protein was significantly increased in non-keratinizing carcinoma compared with
      undifferentiated carcinoma and keratinizing carcinoma (P<0.05 and P<0.05). The
      expression of Wnt5a protein in the NPC had significant positive correlation with
      LMP1 (r=0.354, P<0.001). Combined molecular phenotype of both Wnt5a and LMP1
      expression was a good marker to distinguish NPC from non-cancerous nasopharyngeal
      epithelium. CONCLUSION: The expression of Wnt5a and LMP1 protein in the NPC is
      positively correlated, and both wnt5a and LMP1 protein play important roles in
      the nasopharyngeal carcinogenesis either together or successively promoting the
      malignant transformation of nasopharyngeal epithelium and the development and
      progression of NPC. Both Wnt5a and LMP1 positive expression may act as good
      markers for NPC differential diagnosis.

PMID- 23000759
TI  - [Effect of gallnut extract on nasopharyngeal carcinoma 5-8F cells and its
      mechanism].
AB  - OBJECTIVE: To determine the biological activity of ellagic acid extracted from
      gallnut against nasopharyngeal carcinoma and its molecular mechanism. METHODS:
      Nasopharyngeal carcinoma 5-8F cells were treated with 2, 4, 6 MUg/mL ellagic acid
      for 48 h in vitro. The cell proliferation and cell apoptosis were analyzed by MTT
      and Hoechst33258 stain. The cell cycle and protein expression were measured by
      flow cytometry and Western blot. RESULTS: Ellagic acid inhibited the
      proliferation of 5-8F cells. The inhibition rates were (29.35+/-4.95)%, (53.32 +/
      4.44)% and ( 61.75 + 6.93)%, respectively, with significant difference from the
      control group (P<0.01). S phase cells in the experimental groups were (25.47+/
      0.74)%, (28.08+/-1.41)% and (35.49+/-0.66)%, respectively, with significant
      difference (P<0.01) from the control group (21.26+/-0.70)%. Cells in the
      experimental groups showed nuclear pyknosis, karyorrhexis and poptotic cell
      morphology. The expression of COX-2 and stathmin in 5-8F cells was down-regulated
      with increased drug concentration. CONCLUSION: Ellagic acid extracted from
      gallnut has activity against nasopharyngeal carcinoma cells, and its mechanism
      may be related to down-regulated expression of COX-2 and stathmin.

PMID- 23000760
TI  - [Construction of RNAi targeting TRAF1 gene and effect of TRAF1 on gastric cancer
      cells].
AB  - OBJECTIVE: To construct the RNAi targeting tumor necrosis factor receptor
      associated factor (TRAF1) gene, and to explore the effect of interference
      targeting TRAF1 on the biological behavior of gastric cancer cells. METHODS: We
      detected the expression of TRAF1 in BGC823, SGC7901, and MGC803 gastric cancer
      cell lines through the real-time PCR and Western blot; then we constructed three
      pLVXshRNA- TRAF1-shRNAs expression vector targeting TRAF1. When TRAF1 was
      interfered successfully, we selected the strongest interference efficiency ShRNA
      by real-time PCR and Western blot. Based on interference targeting TRAF1 on
      gastric cancer, we tested the cell proliferation activity and apoptosis through
      MTT assay and flow cytometry, and the cell migration by transwell migration
      assay. RESULTS: The expression of TRAF1 was increased in BGC823, SGC7901, and
      MGC803 gastric cancer cell lines compared with gastric epithelial cells (P<0.05),
      and the highest expression was in BGC823 gastric cell line. In the three TRAF1
      shRNAs, the strongest interference efficiency shRNA was pLVX-shRNA-TRAF1-shRNA2.
      When the gene TRAF1 of BGC823 was interfered, the cell growing power was weakened
      and the apoptosis rate increased, and the cell migration had no difference.
      CONCLUSION: The expression of TRAF1 is up-regulated in gastric cancer cell lines
      BGC823, SGC7901, and MGC803, and the most obvious one is BGC823. The interference
      targeting TRAF1 can successfully inhibit the expression of TRAF1 in gastric
      cancer cell line BGC823. TRAF1 can inhibit the apoptosis of BGC823 cells.

PMID- 23000761
TI  - [Simultaneous inhibition of XIAP and survivin expression on EMT and invasion of
      human pancreatic cancer cells].
AB  - OBJECTIVE: To investigate the simultaneous inhibition of X-linked inhibitor of
      apoptosis protein (XIAP) and survivin expression on epithelial-mesenchymal
      transition (EMT) and invasiion of pancreatic cancer cells Panc-1, and its
      mechanism. METHODS: On the established human pancreatic cancer cells Panc-1-XS,
      the expression of XIAP and survivin was inhibited simultaneously. Cell invasion
      and migration were detected by Transwell chamber experiments and scratch test,
      and the expression of epithelial marker E-cadherin, mesenchymal markers Slug,
      phosphatase and tensin homolog deleted on chromosome ten (PTEN) and P-Akt protein
      was determined by Western blot. RESULTS: Cell invasion and migration of Panc-1-XS
      cells decreased significantly, accompanied by significantly upregulated protein
      expression of E-cadherin, and significantly declined protein expression of the
      Slug, indicating increased mesenchymal-epithelial conversion (MET); and increased
      protein expression of PTEN, and declined protein expression of P-Akt. CONCLUSION:
      Simultaneously inhibiting the expression of XIAP and survivin can partially
      reverse EMT phenotype of pancreatic cancer Panc-1 cells, which then significantly
      reduces the cell invasion and migration of Panc-1 cell lines. This process may be
      regulated by PTEN/PI3K/Akt signaling pathway.

PMID- 23000762
TI  - [Expression of BRAF and its extracellular signal-regulated kinase 1/2 signal
      pathway in papillary thyroid cancer].
AB  - OBJECTIVE: To determine the association between activity of BRAF and mitogen
      activated protein/ extracellular signal-regulated kinase kinase (MEK) /
      extracellular signal-regulated kinase (ERK) signal pathway in papillary thyroid
      cancer and its mechanism. METHODS: We collected the clinical data and blood
      samples from 73 cases of papillary thyroid cancer and another 16 cases of benign
      thyroid gland tumor, and detected the expression of rat sarcoma (RAS), BRAF,
      MEK1/2, and ERK1/2 in all tumor specimens and benign thyroid tissues with
      immunohistochemistry and Western blot. RESULTS: The expression of RAS, BRAF,
      pMEK1/2, and pERK1/2 protein in papillary thyroid cancer tissues was higher than
      those in the benign thyroid tissues(P<0.05 or P<0.01). The expression of RAS,
      BRAF, MEK1/2, and ERK1/2 was associated with the tumor size, the lymph node
      metastasis, and the clinical stage of papillary thyroid cancer(P<0.05 or P<0.01).
      CONCLUSION: The expression of RAS, BRAF, pMEK1/2, and pERK1/2 is associated with
      the pathogenesis, the lymph node metastasis, and the clinical stage of papillary
      thyroid cancer. The MEK/ERK signaling pathway may be activated by BRAF in
      papillary thyroid cancer.

PMID- 23000763
TI  - [Analysis of blood flow in sequential and individual saphenous vein grafts in off
      pump coronary artery bypass grafting].
AB  - OBJECTIVE: To compare the blood flow in sequential and individual saphenous vein
      grafts (SVGs) and to analyze the influence of the location of the target vessel
      in off-pump coronary artery bypass grafting (OPCAB). METHODS: A total of 464 SVGs
      in 412 patients receiving OPCAB were nested into individual SVG (n=206), double
      (n=241) or triple sequential SVG (n=15), and analyzed. RESULTS: The blood flow in
      double and triple SVGs was significantly higher than in individual SVGs [(43.4+/
      22.5), (43.7+/-19.2) and (28.9+/-18.7) mL/min, respectively, P<0.001, P=0.047].
      There were no differences between flow in double and triple SVGs (P=0.96).
      Pulsatility index (PI) of the three groups were similar (2.6+/-1.2, 2.5+/-1.6,
      2.8+/-0.9, respectively, P=0.49, P=0.49). In individual SVGs to right coronary
      artery, the blood flow was higher than in the posterior descending branch (PDA)
      (P=0.047) and posterior branch of left ventricle (PBLV), the flow-time in systole
      period was longer than diagonals (P=0.003), obtuse marginal (OM) (P=0.013) and
      PDA (P=0.002), PI was significantly lower than PDA (P=0.033) and PBLV (P=0.032).
      The blood flow in individual SVGs to diagonals was significantly lower than in
      other target vessels except for PBLV (P<0.05). Flow in double SVGs to PDA-PBLV
      was significantly lower than in PDA-OM. CONCLUSION: The mean blood flow in double
      and triple sequential SVGs is about 1.5 times higher than in individual SVGs.
      Individual, double, and triple SVGs have similar pI. Flow in individual SVGs to
      diagonals was significantly lower than in other target vessels except for PBLV.

PMID- 23000764
TI  - [Relevance of the expression of CTNNAL1 and the resistance of respiratory tract
      in rat with airway hyperresponsiveness].
AB  - OBJECTIVE: To observe the relation between the expression of CTNNAL1 and the
      airway resistance in rats with airway hyperresponsiveness. METHODS: Thirty Wister
      rats were randomly divided into 5 groups: a normal control group, a 2 d ozone
      attack group, a 4 d ozone attack group, a 6 d ozone attack group, and a 6 d ozone
      attack+2 d dexamethasone treatment group (6 rats in each group). The distribution
      of CTNNAL1 was observed by in situ hybridization; the expression of CTNNAL1 was
      detected by fluorescence quantitative RT-PCR; the airway resistance was detected
      in by Buxco pulmonary function analysis system; and the relevance of the
      expression of CTNNAL1 and the resistance of respiratory tract in rat with airway
      hyperresponsiveness were analyzed. RESULTS: CTNNAL1 was distributed in bronchial
      epithelial cells, goblet cells, endothelial cells, and the alveolar wall. With
      the increase of the ozone attack, the expression of CTNNAL1 mRNA gradually
      reduced, the airway hyperresponsiveness was aggravated, and the airway resistance
      was increased. CONCLUSION: During airway hyperresponse, the reduction of CTNNAL1
      mRNA can increase the airway resistance. There is a negative correlation between
      the reduction of CTNNAL1 mRNA and the airway hyperresponsiveness. CTNNAL1 is an
      adhesion molecule related to airway hyperresponsiveness susceptibility.

PMID- 23000765
TI  - [Preventive effect of exogenous hydrogen sulfide on hepatic fibrosis in rats].
AB  - OBJECTIVE: To determine the effect of exogenous hydrogen sulfide on experimental
      hepatic fibrosis in rats and its mechanism. METHODS: Wistar male rats were
      randomly divided into three groups: a normal control group (n=8), a model group
      (n=8), and a hydrogen sulfide prevention group (n=8). The rat model of hepatic
      fibrosis was reduced by intraperitoneal injection of carbon tetrachloride (CCl4).
      The prevention group, in addition to intraperitoneal injection of 40% CCl4, was
      intraperitoneally administered H2S once a day until 8th week. After the
      experiment, the liver function and liver fibrosis were assayed. Liver tissue
      samples were used for histopathological changes. The expression of TGF-beta1 in
      liver tissue was detected by RT-PCR and Western blot. RESULTS: Compared with the
      model group, the levels of ALT, AST, HA, LN, and PC III in the sulfide group were
      significantly reduced (P<0.01 or P<0.05), ALB content was increased (P<0.05) in
      the serum, TGF-beta1 expression was obviously reduced, and the degree of liver
      fibrosis was improved (P<0.05). CONCLUSION: Exogenous hydrogen sulfide can
      effectively inhibit the development of hepatic fibrosis, reduce the expression of
      TGF-beta1, and decrease the the sediment of extracellular matrix in the liver
      tissues.

PMID- 23000766
TI  - [Surgical risks for patients with hepatolithiasis undergoing hepatectomy].
AB  - OBJECTIVE: To evaluate the risk of hepatectomy by detecting liver functional
      reserve preoperatively for patients with primary hepatolithiasis. METHODS: The
      clinical data of 134 patients with primary hepatolithiasis who underwent
      hepatectomy were reviewed. In terms of evaluation methods for preoperative liver
      functional reserve they were divided into a Child-Pugh group (group CP) and an
      indocyanine green group (group ICG). The preoperative and intraoperative
      parameters, and the incidence of postoperative complications were analyzed.
      RESULTS: Liver failure was more common in group CP (12.85%) than that in group
      ICG (1.56%, P<0.05). The overall complication rate in group CP (37.14%) was
      higher than in group ICG (18.75%, P<0.05). CONCLUSION: ICG15 retention test is
      more accurate in evaluating liver functional reserve than Child-Pugh scoring
      system. It may predict the postoperative liver failure in patients with primary
      hepatolithiasis undergoing hepatectomy, decrease postoperative complications, and
      increase operation safety.

PMID- 23000767
TI  - [Reparation of anterior mitral valve prolapse with artificial chord and mitral
      annuloplasty ring].
AB  - OBJECTIVE: To evaluate the effect of mitral annuloplasty of anterior mitral valve
      prolapse with artificial chord and mitral annuloplasty ring. METHODS: From March
      2009 to December 2011, 32 patients having anterior mitral valve prolapse received
      mitral annuloplasty with artificial chord and mitral annuloplasty ring in our
      department, among which 27 simple anterior mitral valve plasty and 5 combine
      anterior-posterior mitral valve plasty were completed. RESULTS: All patients
      survived. Postoperative echocardiography showed no or trivial mitral
      regurgitation in 28 patients and mild mitral regurgitation in the other 4
      patients. The diameter of the left atrium (LA) and left ventricle (LV), left
      ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume
      (LVESV) obviously decreased after the operation. During the follow up of 3 months
      to 3 years, the cardiac function of the patients improved at different degrees.
      CONCLUSION: Reparation of anterior mitral valve prolapse with artificial chord
      and mitral annuloplasty ring is simple, reliable and effective, and its early to
      midterm result after the operation proves good.

PMID- 23000768
TI  - [Risk factors for bloodstream infections in liver or kidney transplantation
      recipients].
AB  - OBJECTIVE: To investigate the possible risk factors for death among liver or
      kidney recipients with bloodstream infections (BSIs). METHODS: A retrospective
      study of 138 episodes of bloodstream infections documented in 103 patients was
      conducted to assess potential risk factors for mortality. The risk factors were
      identified by logistic regression analysis. RESULTS: The mean age of the patients
      was 12-66 (42.3+/-12.7) years. The majority of infections were nosocomial
      (78.6%). The BSIs-related mortality rate was 39.8% (41/103). The following
      variables were identified as risk factors for BSIs-related mortality by
      univariate analysis: intraabdominal/ biliary focus (P=0.003), polymicrobial
      infection (P<0.001), liver transplant (P<0.001), platelet count <50000/mm3
      (P<0.001), and septic shock (P<0.001). Platelet count < 50000/mm3 (P=0.002) and
      septic shock (P<0.001) showed significantly difference between the mortality
      group and the survival groups in the multivariate logistic regression analysis.
      CONCLUSION: Decreased platelet count and septic shock are risk factors for
      increased

PMID- 23000769
TI  - [hMLH1 gene promoter methylation in joint cartilage in patients with
      osteoarthritis].
AB  - OBJECTIVE: To investigate the role of Human MutL homologue 1 (hMLH1) gene
      promoter methylation in the occurrence and development of osteoarthritis (OA).
      METHODS: General DNA was dealt with sodium bisulfite. The methylation of hMLH1
      promoter was detected by methylation-specific PCR (MSP). hMLH1 protein expression
      in joint cartilage was detected by immunohistochemical method. RESULTS: The
      positive percent of hMLH1 promoter methylation in OA patients was higher than
      that in healthy persons (chi(2)=30.634, P<0.001); the positive percent of hMLH1
      protein in OA patients was significantly lower than that in healthy persons
      (chi(2)=37.724, P<0.001); prmoter methylation and protein expression level of
      hMLH1 gene showed negative correlation (rs=-0.554, P<0.001). CONCLUSION: hMLH1
      promoter is hypermethlated in joint cartilage cells of OA patients.
      Hypermethylation may affect the protein expression of hMLH1, which might play a
      role in the occurrence and development of OA.

PMID- 23000770
TI  - [Diagnosis of placenta previa accreta by two dimensional ultrasonography and
      color doppler in patients with cesarean section].
AB  - OBJECTIVE: To determine the accuracy of two dismensional sonography and color
      doppler in diagnosing placenta previa accreta in patients with previous cesarean
      section. METHODS: Forty-one patients with previous cesarean sections were
      confirmed to have partial or total placenta previa in the current pregnancy and
      were given ultrasound examinations after the 28th week of gestation. Specific
      ultrasound features of the placenta and its interphase with the uterus and the
      bladder for placenta accreta were checked by two-dimensional ultrasonography and
      color Doppler. All the patients were traced until delivery. The golden standard
      in diagnosis was the intraoperative finding and the pathologic exam. RESULTS:
      Twenty-two patients had ultrasonographic evidence of placenta previa, 20 of which
      were later confirmed placenta previa accreta intraoperatively. Nineteen patients
      had no ultrasound evidence of placenta previa, and 1 of which was later confirmed
      placenta previa accreta. The sensitivity and specificity of antenatal ultrasound
      diagnosis of placenta previa accreta were 95.24% and 94.74% respectively. The
      most prominent feature to suggest placenta accreta in twodismensional sonography
      was the presence of multiple lakes that represented dilated vessels extending
      from the placenta through the myometrium. The most prominent color Doppler
      feature was the presence of interphase hypervascularity with abnormal vessels
      linking the placenta to the bladder, and the rate was 95.24%. CONCLUSION:
      Placenta previa accreta can be diagnosed made with a thorough two dimensional
      ultrasonographic and color Doppler examination in patients with previous cesarean
      scar and placenta previa.

PMID- 23000771
TI  - [Protective effect of epigallocatechin-3-gallate on apoptosis of rat cerebellar
      granule neurons induced by acrylamide].
AB  - OBJECTIVE: To investigate the protective effect of epigallocatechin-3 -gallate
      (EGCG) on apoptosis of cerebellar granule neurons (CGNs) induced by acrylamide
      (ACR). METHODS: CGNs were cultured with the addition of 5 mmol/L ACR for 24 hours
      to set up a cell injury model. Prior to ACR treatment, CGNs were treated with
      different concentrations of EGCG (0, 5, 10, 25, 50, 100 MUmol/L) for 48 hours.
      Neuronal viability was measured with metylthiazdyltetrazolium (MTT). The activity
      of SOD and the content of MDA were assayed. Hoechst33342 staining was employed to
      observe morphological changes of the cell nucleus. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to measure expression of bcl- 2 mRNA
      and bax mRNA. RESULTS: At the concentrations of 10, 25 or 50 MUmol/L, EGCG played
      a protective role against ACRinduced CGN injury. Compared with ACR injured group
      (no EGCG), EGCG improved the cell viability, enhanced SOD activity, decreased the
      level of MDA as well as the cell apoptosis ratio (P<0.05). Bcl-2 mRNA expression
      was increased and bax mRNA expression was reduced (P<0.05). 25 MUmol/L EGCG had
      the largest effect. However, 100 MUmol/L EGCG did not have a significantly
      protective effect. CONCLUSION: EGCG at appropriate concentration has protective
      effect against the CGNs on apoptosis induced by ACR.

PMID- 23000772
TI  - [Vibration perception threshold in diagnosing diabetic peripheral neuropathy by
      receiver operating characteristic curve].
AB  - OBJECTIVE: To evaluate the diagnostic value of vibration perception threshold
      (VPT) in diabetic peripheral neuropathy (DPN) by the receiver operating
      characteristic curve (ROC) and to establish its cut-off threshold. METHODS: All
      patients had the VPT examination and nerve conduction velocity (NCV) examination.
      NCV examination showed that 283 patients with Type 2 diabetes were divided into a
      DPN group (n=151) and an NDPN group (n=132). The VPT diagnosis was evaluated by
      Youden index, sensitivity, specificity and the area under ROC curve. The best cut
      off threshold was defined by the Youden index. RESULTS: 1) The NCV was
      significantly slower, while the VPT was higher in the DPN group than those in the
      NDPN group (both P values <0.05). 2) The VPT and NCV of both sides of the limb
      had no difference in all patients. 3) With NCV as the golden diagnosis criterion,
      the area under ROC of VPT was 0.707, the best cut-off threshold was 10.54 V, the
      sensitivity was 0.596, the specificity was 0.848, and the Youden index was 0.445.
      4) The diagnosis ratio of NCV combined with VPT was 60.4%, significantly higher
      than that of NCV alone (P<0.05). CONCLUSION: Compared with NCV examination, VPT
      has good diagnostic value for DPN. The best cut-off value is 10.54 V.

PMID- 23000773
TI  - [Label identities and basic situation of health food in Changsha].
AB  - OBJECTIVE: To study the relevant information on the label of health food in
      Changsha, and provide scientific evidence for health food hygienic supervision.
      METHODS: Investigation was conducted in department stores, supermarkets,
      pharmacies, and wholesale markets in the 5 districts in Changsha with multistage
      stratified sampling method. Self designed basic information of health food
      questionnaire was used to investigate the quality of labels the health food
      products. RESULTS: Among the 408 random samples, the unidentified rates of label
      items were ranked in descending order: functional components (49.8%), unsuited
      community (27.9%), manufacturing date (23.0%), approval number and others (9.6%).
      The qualified rates of labels were different in different management types
      (chi(2)=59.793, P<0.05): the highest rate was in supermarkets (71.15%), followed
      by pharmacies (70.07%), shopping malls (57.47%), and wholesale markets (26.23%).
      CONCLUSION: The supervision of label identities of health food should be
      strengthened, especially for the health food in the wholesale markets.

PMID- 23000774
TI  - [Pharmacological intervention of conditioned fear and its extinction].
AB  - Conditioned fear and its abnormal extinction are involved in the psychopathology
      of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive
      enhancing agents have been demonstrated to alter fear extinction in many animal
      research literatures. The present review has examined the pharmacological role of
      gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic,
      dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic
      and neurotrophic mechanism in fear extinction, highlighting great hope for the
      future treatment of anxiety disorders with new agents based on the fear
      extinction.

PMID- 23000776
TI  - [Treatment of pulmonary and retroperitoneal lymphangioleiomyomatosis with
      rapamycin: a case presentation and literature review].
AB  - To improve the diagnosis and treatment of pulmonary lymphangiomyomatosis,
      clinical data for the first successfully treated case of pulmonary and
      retroperitoneal lymphangiomyomatosis in our hospital has been comprehensively
      analyzed, and the relevant literature has been reviewed. A 45-year-old Han
      Chinese woman initially presented six months ago with increasing shortness of
      breath on exertion and was admitted to our hospital after four days of chest
      pain. Admission examination revealed chylothorax, interstitial lung disease, and
      enlarged retroperitoneal lymph nodes. The patient was finally diagnosed with
      pulmonary and retroperitoneal lymphangiomyomatosis based on laparotomy
      examination and biopsy of the retroperitoneal lymph nodes. After six months of
      rapamycin treatment, the symptoms - lung function, arterial blood gas, and
      imaging of the patient- were improved significantly. Pulmonary
      lymphangiomyomatosis clinically manifests as progressive dyspnea, recurrent
      pneumothorax, and chylothorax, and can be diagnosed by its characteristic
      features in high-resolution computed tomographic images or pathological
      examination. The successful treatment of pulmonary lymphangiomyomatosis with
      rapamycin brings new hope to those afflicted with this disease.

PMID- 23000775
TI  - [Telephone follow-up of 1635 post-surgery lung cancer patients and retrospective
      study of lung cancer prognosis].
AB  - OBJECTIVE: To evaluate the telephone follow-up of surgery patients with lung
      cancer and to analyze the prognosis factors. METHODS: From October 2011 to
      January 2012, 1635 post-surgery lung cancer patients from January 2002 to August
      2011 were followed up by telephone interview. The data from follow-up and
      clinical characteristics were collected and analyzed. Among these patients, 116
      patients with complete and reliable clinical data were further analyzed to
      determine the effective factors of lung cancer metastasis and long-term survival.
      RESULTS: The average response rate in the follow-up was 36.1%, and the response
      rate was related to the interval time after the operations. The shorter the
      interval, the higher the response rate. The response rate in female patients was
      higher than that in male patients (P<0.001).The response rate was higher in
      patients younger than 40 (56 %) than that in the patients aged between 50-59 and
      over 60 (39% and 24% respectively, P<0.001). There was no statistical difference
      between patients from urban and rural areas (P=0.844). In the 116 patients with
      complete and reliable clinical data, statistical analysis confirmed that the
      metastasis and high lymph node staging were factors to increase patients' risk of
      death (with odd ratio 0.212 and 1.818 respectively, P<0.001). The adenocarcinoma
      grade, high lymph node staging and advanced age were related to the metastasis
      risk (odds ratio 2.353, 2.181 and 2.908, respectively). CONCLUSION: Time, gender
      and age are the influencing factors in the telephone follow-up. Metastasis, lymph
      node metastasis, pathologic type and age are related to the lung cancer prognosis
      in the small-scale sample.

PMID- 23000777
TI  - Inhibition of Paenibacillus larvae by lactic acid bacteria isolated from
      fermented materials.
AB  - We evaluated the potential application of lactic acid bacteria (LAB) isolated
      from fermented feeds and foods for use as probiotics against Paenibacillus
      larvae, the causal agent of American foulbrood (AFB) in vitro. We also assessed
      the ability of LAB to induce the expression of antimicrobial peptide genes in
      vivo. Screening of the 208 LAB isolated from fermented feeds and foods revealed
      that nine strains inhibited the in vitro growth of P. larvae. The LAB strains
      were identified by 16S rRNA gene sequencing as Enterococcus sp., Weissella sp.
      and Lactobacillus sp. These strains were screened for their abilities of immune
      activation in honeybees by real-time RT-PCR using antimicrobial peptide genes as
      markers. After oral administration of several of the screened LAB to larvae and
      adults, the transcription levels of antimicrobial peptide genes, such as abaecin,
      defensin and hymenoptaecin, were found to increase significantly. These findings
      suggested that selected LAB stimulate the innate immune response in honeybees,
      which may be useful for preventing bacterial diseases in honeybees. This is the
      first report to characterize the probiotic effects of LAB isolated from fermented
      feeds and foods in honeybees.

PMID- 23000778
TI  - Hyperkalaemia or potassophobia?

PMID- 23000779
TI  - Instant MOFs: continuous synthesis of metal-organic frameworks by rapid solvent
      mixing.
AB  - A continuous flow reactor allows the preparation of porous metal-organic
      framework materials with crystallisation induced by rapid mixing of streams of
      preheated water and solutions of reagents in organic solvent: this gives high
      volume production (132 g h(-1)) with crystallite size of the products from
      nanoscale to micron.

PMID- 23000780
TI  - Replacing car trips by increasing bike and public transport in the greater
      Barcelona metropolitan area: a health impact assessment study.
AB  - OBJECTIVE: Estimate the health risks and benefits of mode shifts from car to
      cycling and public transport in the metropolitan area of Barcelona, Spain.
      METHODS: We conducted a health impact assessment (HIA), creating 8 different
      scenarios on the replacement of short and long car trips, by public transport
      or/and bike. The primary outcome measure was all-cause mortality and change in
      life expectancy related to two different assessments: A) the exposure of
      travellers to physical activity, air pollution to particulate matter <2.5 MUm
      (PM2.5), and road traffic fatality; and B) the exposure of general population to
      PM2.5, modelling by Barcelona Air-Dispersion Model. The secondary outcome was a
      change in emissions of carbon dioxide. RESULTS: The annual health impact of a
      shift of 40% of the car trips, starting and ending in Barcelona City, to cycling
      (n=141,690) would be for the travellers who shift modes 1.15 additional deaths
      from air pollution, 0.17 additional deaths from road traffic fatality and 67.46
      deaths avoided from physical activity resulting in a total of 66.12 deaths
      avoided. Fewer deaths would be avoided annually if half of the replaced trips
      were shifted to public transport (43.76 deaths). The annual health impact in the
      Barcelona City general population (n=1,630,494) of the 40% reduction in car trips
      would be 10.03 deaths avoided due to the reduction of 0.64% in exposure to PM2.5.
      The deaths (including travellers and general population) avoided in Barcelona
      City therefore would be 76.15 annually. Further health benefits would be obtained
      with a shift of 40% of the car trips from the Greater Barcelona Metropolitan
      which either start or end in Barcelona City to public transport (40.15 deaths
      avoided) or public transport and cycling (98.50 deaths avoided).The carbon
      dioxide reduction for shifting from car to other modes of transport (bike and
      public transport) in Barcelona metropolitan area was estimated to be 203,251t/CO2
      emissions per year. CONCLUSIONS: Interventions to reduce car use and increase
      cycling and the use of public transport in metropolitan areas, like Barcelona,
      can produce health benefits for travellers and for the general population of the
      city. Also these interventions help to reduce green house gas emissions.

PMID- 23000782
TI  - What is evidence based in the reconstruction of digital nerves? A systematic
      review.
AB  - BACKGROUND: An intact digital nerve is obligatory for hand function. When
      transected, the hand surgeon has several options. However, there is no hard
      evidence which technique to choose. OBJECTIVE: The aim of this study was to
      provide an evidence-based overview of the effectiveness of interventions used in
      reconstruction and post-surgical management of digital nerve injuries. METHODS:
      The Cochrane Library, PubMed, EMBASE, CINAHL and PEDro databases were searched.
      Two reviewers independently applied the inclusion criteria to select potential
      relevant randomised controlled trials (RCTs) and controlled clinical trials
      (CCTs), extracted data and performed a methodological quality assessment of the
      included studies. The Grades of Recommendation, Assessment, Development and
      Evaluation (GRADE) method was used to summarise the results. RESULTS: Eight RCTs
      were included, five on surgical and three on post-surgical interventions. Low
      quality evidence was found for effectiveness in favour of a polyglycolic acid
      conduit compared to primary neurrorhaphy or autologous graft, in digital nerve
      gaps of <=4 mm and >=8 mm at long-term follow-up. Very low quality of evidence
      was found for effectiveness in favour of EMLA creme, compared to placebo, in
      enhancing sensory relearning for the short-term, but not for the long-term
      outcomes. Low quality of evidence was found for effectiveness in favour of
      sensory re-education compared with control at long-term follow-up. For other
      interventions, no evidence for effectiveness was found. CONCLUSIONS: Indications
      for effectiveness of some treatment strategies in digital nerve repair were
      found, but due to a minimal number of RCTs in this field no firm conclusions
      could be drawn for the different techniques. More high-quality RCTs are needed
      for a more confident estimate of effect. LEVEL OF EVIDENCE: Therapeutic II.

PMID- 23000784
TI  - The emergence of abnormal hypersynchronization in the anatomical structural
      network of human brain.
AB  - Brain activity depends on transient interactions between segregated neuronal
      populations. While synchronization between distributed neuronal clusters reflects
      the dynamics of cooperative patterns, the emergence of abnormal cortical
      hypersynchronization is typically associated with spike-wave discharges, which
      are characterized by a sudden appearance of synchronous around 3Hz large
      amplitude spike-wave discharges of the electroencephalogram. While most existing
      studies focus on the cellular and synaptic mechanisms, the aim of this article is
      to study the role of structural connectivity in the origin of the large-scale
      synchronization of the brain. Simulating oscillatory dynamics on a human brain
      network, we find the space-time structure of the coupling defined by the
      anatomical connectivity and the time delays can be the primary component
      contributing to the emergence of global synchronization. Our results suggest that
      abnormal white fiber connections may facilitate the generation of spike-wave
      discharges. Furthermore, while neural populations can exhibit oscillations in a
      wide range of frequency bands, we show that large-scale synchronization of the
      brain only occurs at low frequencies. This may provide a potential explanation
      for the low characteristic frequencies of spike-wave discharges. Finally, we find
      the global synchronization has a clear anterior origin involving discrete areas
      of the frontal lobe. These observations are in agreement with existing brain
      recordings and in favor of the hypothesis that initiation of spike-wave
      discharges originates from specific brain areas. Further graph theory analysis
      indicates that the original areas are highly ranked across measures of
      centrality. These results underline the crucial role of structural connectivity
      in the generation of spike-wave discharges.

PMID- 23000783
TI  - Altered anterior insula activation during anticipation and experience of painful
      stimuli in expert meditators.
AB  - Experientially opening oneself to pain rather than avoiding it is said to reduce
      the mind's tendency toward avoidance or anxiety which can further exacerbate the
      experience of pain. This is a central feature of mindfulness-based therapies.
      Little is known about the neural mechanisms of mindfulness on pain. During a
      meditation practice similar to mindfulness, functional magnetic resonance imaging
      was used in expert meditators (>10,000 h of practice) to dissociate neural
      activation patterns associated with pain, its anticipation, and habituation.
      Compared to novices, expert meditators reported equal pain intensity, but less
      unpleasantness. This difference was associated with enhanced activity in the
      dorsal anterior insula (aI), and the anterior mid-cingulate (aMCC) the so-called
      'salience network', for experts during pain. This enhanced activity during pain
      was associated with reduced baseline activity before pain in these regions and
      the amygdala for experts only. The reduced baseline activation in left aI
      correlated with lifetime meditation experience. This pattern of low baseline
      activity coupled with high response in aIns and aMCC was associated with enhanced
      neural habituation in amygdala and pain-related regions before painful
      stimulation and in the pain-related regions during painful stimulation. These
      findings suggest that cultivating experiential openness down-regulates
      anticipatory representation of aversive events, and increases the recruitment of
      attentional resources during pain, which is associated with faster neural
      habituation.

PMID- 23000785
TI  - Morphology and microstructure of subcortical structures at birth: a large-scale
      Asian neonatal neuroimaging study.
AB  - This paper presents the growth pattern and sexual dimorphism of the thalamus and
      basal ganglia in a large-scale Asian neonatal cohort using both T2-weighted
      magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Our study
      observed a robust growth of the thalamus and basal ganglia (caudate, putamen,
      globus pallidus, and anterior limb of internal capsule) beyond the overall brain
      growth in the early postnatal period (36-43 weeks of the gestational age).
      Additionally, the microstructure of the two structures was integrated as
      reflected by an increase in fractional anisotropy (FA) and a decrease in axial
      and radial water diffusivities in the first few weeks of life. Sexual dimorphism
      was only observed in the whole brain growth and the left thalamic volume but not
      in the other volumes or DTI measures of the basal ganglia and thalamus at birth.
      Even though the pattern of sexual dimorphism in the total brain volume is present
      at birth and persists throughout postnatal brain development, sexual dimorphisms
      of the basal ganglia and thalamus differ from those found in later stages of
      brain development, indicating that regionally distinct patterns of postnatal
      brain development between males and females arise after birth.

PMID- 23000787
TI  - Imaging hypothalamic activity using diffusion weighted magnetic resonance imaging
      in the mouse and human brain.
AB  - Hypothalamic appetite regulation is a vital homeostatic process underlying global
      energy balance in animals and humans, its disturbances resulting in feeding
      disorders with high morbidity and mortality. The objective evaluation of appetite
      remains difficult, very often restricted to indirect measurements of food intake
      and body weight. We report here, the direct, non-invasive visualization of
      hypothalamic activation by fasting using diffusion weighted magnetic resonance
      imaging, in the mouse brain as well as in a preliminary study in the human brain.
      The brain of fed or fasted mice or humans were imaged at 7 or 1.5 Tesla,
      respectively, by diffusion weighted magnetic resonance imaging using a complete
      range of b values (10<b<2000s.mm(-2)). The diffusion weighted image data sets
      were registered and analyzed pixel by pixel using a biexponential model of
      diffusion, or a model-free Linear Discriminant Analysis approach. Biexponential
      fittings revealed statistically significant increases in the slow diffusion
      parameters of the model, consistent with a neurocellular swelling response in the
      fasted hypothalamus. Increased resolution approaches allowed the detection of
      increases in the diffusion parameters within the Arcuate Nucleus, Ventromedial
      Nucleus and Dorsomedial Nucleus. Independently, Linear Discriminant Analysis was
      able to classify successfully the diffusion data sets from mice and humans
      between fed and fasted states. Present results are consistent with increased
      glutamatergic neurotransmission during orexigenic firing, a process resulting in
      increased ionic accumulation and concomitant osmotic neurocellular swelling. This
      swelling response is spatially extendable through surrounding astrocytic networks
      until it becomes MRI detectable. Present findings open new avenues for the
      direct, non-invasive, evaluation of appetite disorders and other hypothalamic
      pathologies helping potentially in the development of the corresponding
      therapies.

PMID- 23000786
TI  - Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity
      of the default mode network.
AB  - The balance between excitatory glutamatergic projection neurons and inhibitory
      GABAergic interneurons determines the function of cortical microcircuits. How
      these neurotransmitters relate to the functional status of an entire macro-scale
      network remains unknown. The posteromedial cortex (PMC) is the default mode
      network (DMN) node with the greatest functional connectivity; therefore, we
      hypothesized that PMC glutamate and GABA predict intrinsic functional
      connectivity (iFC) across the entire DMN. In 20 healthy men, we combined J
      resolved magnetic resonance spectroscopy to measure glutamate and GABA in the PMC
      and resting fMRI followed by group Independent Components Analysis to extract the
      entire DMN. We showed that, controlling for age and partial GM volume in the MRS
      voxel, PMC glutamate and GABA explained about half of the variance of DMN iFC
      (represented by the network's beta coefficient for rest). Glutamate correlated
      positively and GABA correlated negatively with DMN iFC; in an alternative
      statistical model which included the glutamate/GABA ratio, the ratio correlated
      positively with DMN iFC. Age had no independent association with DMN iFC. No
      other network was associated with PMC glutamate or GABA. We conclude that
      regional neurotransmitter concentrations in a network node strongly predict
      network but not global brain iFC.

PMID- 23000788
TI  - Statistical shape analysis of the corpus callosum in Schizophrenia.
AB  - We present a statistical shape-analysis framework for characterizing and
      comparing morphological variation of the corpus callosum. The midsagittal
      boundary of the corpus callosum is represented by a closed curve and analyzed
      using an invariant shape representation. The shape space of callosal curves is
      endowed with a Riemannian metric. Shape distances are given by the length of
      shortest paths (geodesics) that are invariant to shape-confounding
      transformations. The statistical framework enables computation of shape averages
      and covariances on the shape space in an intrinsic manner (unique to the shape
      space). The statistical framework makes use of the tangent principal component
      approach to achieve dimension reduction on the space of corpus callosum shapes.
      The advantages of this approach are - it is fully automatic, invariant, and
      avoids the use of landmarks to define shapes. We applied our method to determine
      the effects of sex, age, schizophrenia and schizophrenia-related genetic
      liability on callosal shape in a large sample of patients and controls and their
      first-degree relatives (N=218). Results showed significant age, sex, and
      schizophrenia effects on both global and local callosal shape structure.

PMID- 23000789
TI  - Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood
      flow and oxygen extraction fraction in stroke mice.
AB  - Many brain diseases have been linked to abnormal oxygen metabolism and blood
      perfusion; nevertheless, there is still a lack of robust diagnostic tools for
      directly imaging cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood
      flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the
      balance between CMRO(2) and CBF. This study employed the recently developed in
      vivo (17)O MR spectroscopic imaging to simultaneously assess CMRO(2), CBF and OEF
      in the brain using a preclinical middle cerebral arterial occlusion mouse model
      with a brief inhalation of (17)O-labeled oxygen gas. The results demonstrated
      high sensitivity and reliability of the noninvasive (17)O-MR approach for rapidly
      imaging CMRO(2), CBF and OEF abnormalities in the ischemic cortex of the MCAO
      mouse brain. It was found that in the ischemic brain regions both CMRO(2) and CBF
      were substantially lower than that of intact brain regions, even for the mildly
      damaged brain regions that were unable to be clearly identified by the
      conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions.
      This study demonstrates a promising (17)O MRI technique for imaging abnormal
      oxygen metabolism and perfusion in the diseased brain regions. This (17)O MRI
      technique is advantageous because of its robustness, simplicity, noninvasiveness
      and reliability: features that are essential to potentially translate it to human
      patients for early diagnosis and monitoring of treatment efficacy.

PMID- 23000793
TI  - Mitochondria: getting together.

PMID- 23000795
TI  - Women's awareness of liberalization of abortion law and knowledge of place for
      obtaining services in Nepal.
AB  - In Nepal, following the liberalization of the abortion law, expansion and scaling
      up of services proceeded in parallel with efforts to create awareness of the
      legalization status of abortion and provide women with information about where
      services are available. This article assesses the effectiveness of these
      programmatic interventions in the early years of the country's abortion program.
      Data from a 2006 national survey are analyzed with 2 outcome measures-awareness
      of the legal status of abortion and knowledge of places to obtain abortion
      services among women ages 15 to 44 years. The variations in the outcomes are
      analyzed by ecological-development subregion, residence, education, household
      wealth quintile, age, and number of living children. Bivariate and multivariate
      logistic regression techniques are used. Overall 32.3% (95% confidence interval =
      31.4% to 33.2%) of the respondents were aware of the legal status of abortion and
      56.5% (95% confidence interval = 55.5% to 57.4%) knew of a place where they could
      obtain an abortion. Both outcome measures showed considerable variations by the
      covariates. Women with secondary or higher level of education had the highest
      odds ratio of being aware of the law and having knowledge of a source for
      abortion services. Ecological-development subregions showed the second highest
      levels of odds ratios. Significant disparities among the population subgroups
      existed in the diffusion of awareness of the legal status of abortion and having
      knowledge of a place for abortion services in Nepal. The results point to which
      population subgroups to focus on and also serve as a baseline for assessing
      future progress in the diffusion process. 

PMID- 23000796
TI  - Association between childhood asthma and chronic obstructive pulmonary disease in
      later life.
AB  - Persistent chronic inflammation and impaired lung growth due to asthma in
      childhood may have long-term impact on pulmonary function and increase
      susceptibility to chronic obstructive pulmonary disease (COPD) in later life. To
      investigate whether childhood asthma is associated with adult lung function and
      the risk of developing COPD among Japanese older adults, a case-control study was
      conducted in central Japan. A total of 300 patients with COPD aged 50 to 75 years
      were referred by respiratory physicians, while 400 controls were recruited from
      the community. All participants underwent spirometric measurements of lung
      function. Information on childhood asthma, demographic characteristics, and
      lifestyle characteristics was obtained by face-to-face interview using a
      structured questionnaire. The prevalence of childhood asthma was higher (P =
      .015) among the cases (6.3%) than among the control group (2.4%). Childhood
      asthma was significantly associated with the risk of COPD (adjusted odds ratio
      3.32, 95% confidence interval 1.05-10.45). Participants with childhood asthma had
      lower (P = .010) forced expiratory volume in 1 second (mean 1.63 L, standard
      deviation [SD] 0.64 L) than those without (mean 2.04 L, SD 0.75 L). However, the
      adjusted lung function difference did not attain statistical significance after
      controlling for confounding variables such as age and cumulative smoking
      exposure. The epidemiological evidence suggested a positive association between
      childhood asthma and COPD in later life. Further study of the effect of adequate
      childhood asthma treatment on future risk of COPD should be undertaken. 

PMID- 23000794
TI  - Group choreography: mechanisms orchestrating the collective movement of border
      cells.
AB  - Cell movements are essential for animal development and homeostasis but also
      contribute to disease. Moving cells typically extend protrusions towards a
      chemoattractant, adhere to the substrate, contract and detach at the rear. It is
      less clear how cells that migrate in interconnected groups in vivo coordinate
      their behaviour and navigate through natural environments. The border cells of
      the Drosophila melanogaster ovary have emerged as an excellent model for the
      study of collective cell movement, aided by innovative genetic, live imaging, and
      photomanipulation techniques. Here we provide an overview of the molecular
      choreography of border cells and its more general implications.

PMID- 23000797
TI  - Food frequency questionnaire is a valid tool for the assessment of dietary habits
      of South Indian pregnant women.
AB  - The food frequency questionnaire (FFQ) was validated against multiple 24-hour
      dietary recalls (24-HDRs) and for a few blood biomarkers in 154 pregnant women at
      the obstetrics and gynecology department of St John's Medical College Hospital,
      Bangalore, India. Absolute nutrient intakes from the FFQ correlated positively
      with the average 24-HDR during pregnancy. Energy-adjusted nutrients from the FFQ
      in all trimesters, except proteins, carbohydrate, folate intake, and vitamin B6
      in the third trimester, correlated positively with average 24-HDR. Overestimation
      by the FFQ compared with the 24-HDR ranged from 9% to 41%. Vitamin B12 status in
      the first and second trimesters positively correlated with energy-adjusted and
      absolute vitamin B12 intakes from the FFQ. The Bland Altman plots showed a
      pattern such that a trend was seen toward underreporting of intakes through the
      FFQ, with increasing mean intakes by the 2 methods, considering 24-HDR as the
      reference tool. We conclude that the FFQ is a valid tool to measure dietary
      intakes during pregnancy. 

PMID- 23000798
TI  - The environment modifies the relationship between social networks and secondhand
      smoke exposure among Korean nonsmokers in Seoul and California.
AB  - This study compared risks of secondhand smoke exposure (SHSe) among Korean
      nonsmokers in Seoul, South Korea and California, United States. Social networks
      were hypothesized to contain more smokers in Seoul than in California, and
      smokers were hypothesized to produce more secondhand smoke in Seoul than
      California, as Seoul's policies and norms are less restrictive. Telephone
      interviews were conducted with Korean adults in Seoul (N = 500) and California (N
      = 2830). In all, 69% (95% confidence interval [CI] = 64-74) of Koreans and 31%
      (95% CI = 29-33) of Korean Americans reported any SHSe. A total of 44% (95% CI =
      40-47) of Korean family members smoked versus 29% (95% CI = 28-30) of Korean
      American family members (t = 7.84, P < .01). A 25% to 75% increase in the
      proportion of family members that smoked corresponded with a 13% (95% CI = 5-21)
      higher probability of any SHSe among Koreans compared with 6% (95% CI = 2-10)
      among Korean Americans. Network interventions in combination with policies and/or
      health campaigns may help reduce SHSe globally. 

PMID- 23000799
TI  - Heterogeneity in obesity status and cardiovascular risks in multiethnic Asian
      female immigrants in South Korea.
AB  - The present study investigated the prevalence of obesity and the associated
      health conditions of multiethnic Asian female immigrants in Korea. Data were
      collected from 2246 immigrant wives in 7 largest ethnic groups in a national
      health examination program. The mean body mass index was 21.9 +/- 3.3 kg/m(2).
      Prevalence of obesity (body mass index >=25 kg/m(2)) among immigrant women was
      15.4%. Age-adjusted prevalence of obesity varied among groups by native country
      (from 10.4% for Japanese to 36.3% for Thai women). The likelihood of obesity
      significantly increased with years of residence in Korea (odds ratio [OR] = 1.44
      for 5.0-9.9 years; 1.85 for >=10 years), physical inactivity (OR = 1.84), and
      eating spicy and/or salty food (OR = 1.45). Prevalence of chronic health
      conditions also differed by country of origin. Significant associations were
      observed between obesity and elevated blood pressure (OR = 1.87), obesity and
      elevated cholesterol level (OR = 2.83), and obesity and prediabetes/diabetes (OR
      = 2.44) after adjusting for age, country of origin, and years of residence in
      Korea. 

PMID- 23000800
TI  - Identification of carriers among individuals recruited in the typhoid registry in
      Malaysia using stool culture, polymerase chain reaction, and dot enzyme
      immunoassay as detection tools.
AB  - Chronic carriers of Salmonella Typhi act as reservoirs for the organism and
      become the agents of typhoid outbreaks in a community. In this study, chronic
      carriers in Kelantan, Malaysia were first identified using the culture and
      polymerase chain reaction method. Then, a novel serological tool, designated
      Typhidot-C, was evaluated in retrospect using the detected individuals as control
      positives. Chronic carriage positive by the culture and polymerase chain reaction
      method was recorded at 3.6% (4 out of 110) among individuals who previously had
      acute typhoid fever and a 9.4% (10 out of 106) carriage rate was observed among
      food handlers screened during outbreaks. The Typhidot-C assay was able to detect
      all these positive carriers showing its potential as a viable carrier screening
      tool and can be used for efficient detection of typhoid carriers in an endemic
      area. These findings were used to establish the first carrier registry for S
      Typhi carriers in Malaysia. 

PMID- 23000801
TI  - Verbal short-term memory development and spoken language outcomes in deaf
      children with cochlear implants.
AB  - OBJECTIVES: Cochlear implants (CIs) help many deaf children achieve near-normal
      speech and language (S/L) milestones. Nevertheless, high levels of unexplained
      variability in S/L outcomes are limiting factors in improving the effectiveness
      of CIs in deaf children. The objective of this study was to longitudinally assess
      the role of verbal short-term memory (STM) and working memory (WM) capacity as a
      progress-limiting source of variability in S/L outcomes after CI in children.
      DESIGN: Longitudinal study of 66 children with CIs for prelingual severe-to
      profound hearing loss. Outcome measures included performance on digit span
      forward (DSF), digit span backward (DSB), and four conventional S/L measures that
      examined spoken-word recognition (Phonetically Balanced Kindergarten word test),
      receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition
      skills (Hearing in Noise Test), and receptive and expressive language functioning
      (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score;
      CELF). RESULTS: Growth curves for DSF and DSB in the CI sample over time were
      comparable in slope, but consistently lagged in magnitude relative to norms for
      normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%,
      respectively, of the CI sample scored more than 1 SD below the normative mean for
      raw scores across all ages. The first (baseline) DSF score significantly
      predicted all endpoint scores for the four S/L measures, and DSF slope (growth)
      over time predicted CELF scores. DSF baseline and slope accounted for an
      additional 13 to 31% of variance in S/L scores after controlling for conventional
      predictor variables such as: chronological age at time of testing, age at time of
      implantation, communication mode (auditory-oral communication versus total
      communication), and maternal education. Only DSB baseline scores predicted
      endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes
      were not significantly related to any endpoint S/L measures. DSB baseline scores
      and slopes taken together accounted for an additional 4 to 19% of variance in S/L
      endpoint measures after controlling for the conventional predictor variables.
      CONCLUSIONS: Verbal STM/WM scores, process measures of information capacity,
      develop at an average rate in the years after cochlear implantation, but were
      found to consistently lag in absolute magnitude behind those reported for normal
      hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes,
      but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM
      processing skills reflect important underlying core elementary neurocognitive
      functions and represent potential intervention targets for improving endpoint S/L
      outcomes in pediatric CI users.

PMID- 23000806
TI  - Forensic odontology in the disaster victim identification process.
AB  - Disaster victim identification (DVI) is an intensive and demanding task involving
      specialists from various disciplines. The forensic dentist is one of the key
      persons who plays an important role in the DVI human identification process. In
      recent years, many disaster incidents have occurred that challenged the DVI team
      with various kinds of difficulties related to disaster management and unique
      situations in each disaster. New technologies have been developed to make the
      working process faster and more effective and the different DVI protocols have
      been evaluated and improved. The aim of this article is to collate all
      information regarding diagnostic tools and methodologies pertaining to forensic
      odontological DVI, both current and future.  It can be concluded that lessons
      learned from previous disaster incidents have helped to optimize working
      protocols and to develop new tools that can be applied in future DVI operation.
      The working procedures have been greatly improved by newly developed
      technologies.

PMID- 23000807
TI  - Injuries to the head and face in Brazilian adolescents and teenagers victims of
      non-natural deaths.
AB  - This study aimed to evaluate the occurrence of injuries to the head and face in
      adolescent and teenager victims of non-natural deaths. A retrospective study was
      undertaken by the analysis of medical forensic reports obtained from medical
      forensic examinations performed at the Department of Forensic Medicine of the
      city of Campina Grande, PB, Brazil, between January 2003 and December 2007. From
      a total of 607 reports issued during this time span, the study sample consisted
      of 423 reports (69.6%) referring to adolescents and teenagers of both genders,
      aged 12 to 18 years, who were confirmed to have  died from external causes. The
      causes of death were encoded according to the Chapter XX of the International
      Statistical Classification of Diseases and Related Health Problems (ICD-10). The
      majority of victims were 17 year old males (25.8%). Firearms (33.3%) and
      transport accidents (32.2%) were the most common causes of death, with boys
      showing a 3.7 times greater likelihood of getting killed by firearms than girls.
      There was statistically significant relationship between the occurrence of
      transport accidents and gender. The majority of victims (71.6%) presented with
      multiple injuries throughout the body. There was statistically significant
      relationship between the occurrence of transport accidents and the presence of
      multiple injuries. A high percentage of the victims presented with injuries to
      the head and face. There was statistically significant relationship between the
      occurrence of transport accidents and the presence of injury to the head. Fatal
      gunshot wounds and transport accidents were the main causes of death of male
      adolescents and teenagers. The victims presented with multiple injuries,
      especially to the head and face, and the mandible was the most frequently injured
      facial bone. .

PMID- 23000808
TI  - The tooth for molecular analysis and identification : a forensic approach.
AB  - The aim of this study is to optimize laboratory preparation of teeth for DNA
      identification. By sectioning the tooth topographically into two different
      radicular portions, it was analyzed whether these portions of mineralized tissue
      differ in the quantity and quality of DNA they contain. 25 teeth were subject to
      different experimental conditions and total DNA was quantified for each
      individual tooth's radicular portion: apical and remaining root, according to a
      2003 study by Gaytemenn and Sweet. We verified, with statistically significant
      figures, that the apical portion of the tooth is that which contains the greatest
      quantity of DNA. Different analytical procedures were studied for various
      polymorphic markers to evaluate the quality of the DNA. We concluded that the
      tooth is topographically distinct in both DNA quantity and quality. The tooth's
      apical portion is the preferential choice in sample preparation of dental
      mineralized tissue for molecular analysis and identification.

PMID- 23000809
TI  - Cementum made more visual.
AB  - Dental cementum is a specialized calcified structure covering the root of a
      tooth. This study aims to investigate cementum using various stains which can be
      exceedingly useful in investigation, observation and diagnosis. 4um sections of
      25 extracted normal teeth, 25 cases of various cemental pathologies and 25 ground
      sections were stained using cresyl violet, H/E, toluidine blue and periodic acid
      Schiff and were observed under light and florescence microscopes. Cresyl violet
      showed best contrast amongst all stains in decalcified and ground sections under
      light and florescence microscopy. Under the fluorescence microscope, cementum
      floresced more distinctly than dentin and enamel. Among the cemental pathologies
      examined, osteoid and cementoid exhibited florescence but cementum and bone did
      not fluoresce. Incremental lines were prominently visualised with cresyl violet
      under fluorescent microscopy, which may aid in forensic determination of age. The
      present results demonstrate that cementum in normal decalcified teeth and cemento
      osseous lesions, could be observed best using cresyl violet stain under
      florescence microscopy.

PMID- 23000810
TI  - Sex determination by linear measurements of palatal bones and skull base.
AB  - Genetically determined sexual dimorphism is not restricted to reproductive
      organs. All body structures show sexual differences which emerge during puberty
      and persist lifelong. The aim of this study is to obtain a reliable method for
      sex determination through the analysis of linear measurements of palate bones and
      skull base. One hundred skulls of both sexes, 50 from males and 50 from females,
      aged between 22 and 55 years, from the Sao Goncalo Cemetery of Cuiaba, capital of
      Mato Grosso state, Brazil, were analyzed. Distances between  the incisive
      foramen, right and left greater palatine foramens and the basion were measured
      with a digital caliper. Finally, data were tabulated and statistically analyzed.
      Measurements showed significant sexual dimorphism, except the distance between
      the right and the left greater palatine foramens. The superior expression of sex
      dimorphism corresponded to the distance from the basion to the incisive foramen.
      The authors obtained two mathematical models for sex determination, with a
      reliability rate of 63% and 65% respectively.

PMID- 23000812
TI  - Surface growth of a motile bacterial population resembles growth in a chemostat.
AB  - The growth behavior in well-mixed bacterial cultures is relatively well
      understood. However, bacteria often grow in heterogeneous conditions on surfaces
      where their growth is dependent on spatial position, especially in the case of
      motile populations. For such populations, the relation between growth, motility
      and spatial position is unclear. We developed a microscope-based assay for
      quantifying in situ growth and gene expression in space and time, and we observe
      these parameters in populations of Escherichia coli swimming in galactose soft
      agar plates. We find that the bacterial density and the shape of the motile
      population, after an initial transient, are constant in time. By considering not
      only the advancing population but also the fraction that lags behind, we propose
      a growth model that relates spatial distribution, motility and growth rate. This
      model, that is similar to bacterial growth in a chemostat predicts that the
      fraction of the population lagging behind is inversely proportional to the
      velocity of the motile population. We test this prediction by modulating motility
      using inducible expression of the flagellar sigma factor FliA. Finally, we
      observe that bacteria in the chemotactic ring express higher relative levels of
      the chemotaxis and galactose metabolism genes fliC, fliL and galE than those that
      stay behind in the center of the plate.

PMID- 23000811
TI  - The variability of lower third molar development in Northeast Malaysian
      population with application to age estimation.
AB  - This study aimed to assess the variability of the lower third molar (tooth 38 and
      48) development in Northeast Malaysian population with respect to the side of
      dentition, to generate age prediction models and to compare the outcome with
      other studies. A total of 1080 orthopantomograms of Northeast Malaysian
      population aged between 14 and 25 years (540 males and 540 females) from the
      Hospital Universiti Sains Malaysia's archive which met the inclusion and
      exclusion criteria were selected and the maturity stages of tooth 38 and 48 were
      scored using Demirjian's stages (A-H). The findings showed a wide variation of
      the development of lower third molars in the Northeast Malaysian population. The
      roots developed earlier in males than in females. The development of the
      dentition on opposite sides of the mandible was synchronously in females and
      males. A multiple regression analysis shows that 71.1% of variance in age was
      explained by sex and developmental stage of tooth 48. An age prediction model was
      generated from the regression analysis: [Age = 7.117 + 1.907*(stage of tooth 48) 
      0.432*(sex)] with mean prediction errors between -0.17 to 3.14 years. The
      obtained data in the current study are useful for references and determining age
      of unidentified human remains for identification investigation.

PMID- 23000814
TI  - Influence of sodium chloride on the regulation of Krebs cycle intermediates and
      enzymes of respiratory chain in mungbean (Vigna radiata L. Wilczek) seedlings.
AB  - The effect of common salt (NaCl) on ion contents, Krebs cycle intermediates and
      its regulatory enzymes was investigated in growing mungbean (Vigna radiata L.
      Wilczek, B 105) seedlings. Sodium and chloride ion contents increased in both
      root and shoot whereas potassium ion content decreased in shoot of test seedlings
      with increasing concentrations of NaCl. Organic acids like pyruvate and citrate
      levels increased whereas malate level decreased under stress in both roots and
      shoots. Salt stress also variedly affected the activities of different enzymes of
      respiratory chain. The activity of pyruvate dehydrogenase (E.C. 1.2.4.1)
      decreased in 50 mM NaCl but increased in 100 mM and 150 mM concentrations, in
      both root and shoot samples. Succinate dehydrogenase (E.C. 1.3.5.1) activity was
      reduced in root whereas stimulated in shoot under increasing concentrations of
      salt. The activity of isocitrate dehydrogenase (E.C. 1.1.1.41) and malate
      dehydrogenase (E.C. 1.1.1.37) decreased in both root and shoot samples under salt
      stress. On the contrary, pretreatment of mungbean seeds with sublethal dose of
      NaCl was able to overcome the adverse effects of stress imposed by NaCl to
      variable extents with significant alterations of all the tested parameters,
      resulting in better growth and efficient respiration in mungbean seedlings. Thus,
      plants can acclimate to lethal level of salinity by pretreatment of seeds with
      sublethal level of NaCl, which serves to improve their health and production
      under saline condition, but the sublethal concentration of NaCl should be
      carefully chosen.

PMID- 23000815
TI  - Promoter activities of genes encoding beta-galactosidases from Arabidopsis a1
      subfamily.
AB  - Promoter regions of each of the six AtBGAL gene of the subfamily a1 of
      Arabidopsis thaliana were used to drive the expression of the beta-glucuronidase
      gene. The pattern of promoters (pAtBGAL) activity was followed by histological
      staining during plant development. pAtBGAL1, pAtBGAL3 and pAtBGAL4 showed a
      similar activity pattern, being stronger in cells and organs in expansion, and
      the staining decreasing when cell expansion decreased with age. That indicates a
      consistent involvement of the encoded beta-galactosidases in cells undergoing
      cell wall extension or remodelling in cotyledons, leaves and flower buds. These
      promoters were also active in the calyptra cells and in pollen grains. pAtBGAL2
      activity showed a clear relationship with hypocotyl elongation in both light and
      dark conditions and, like pAtBGAL1, pAtBGAL3 and pAtBGAL4, it was detected during
      the expansion of cotyledons, rosette leaves and cauline leaves. Its activity was
      also intense in the early stages of flower and fruit development. pAtBGAL5 was
      the only one among those from the subfamily a1 that was active in the trichomes
      that appear throughout the plant, indicating a high specificity of the AtBGAL5
      protein and its involvement in the cell wall changes that accompany the formation
      of the trichome. The activity of pAtBGAL5 was also high in radicles and roots,
      except in the meristematic area of these organs, and during seed formation.
      Finally, the activity of pAtBGAL12 was mainly detected in meristematic zones of
      the plant: the leaf primordium, emerging secondary roots and developing seeds,
      which indicates an involvement in the differentiation process.

PMID- 23000816
TI  - Influence of arbuscular mycorrhizal colonisation on cadmium induced Medicago
      truncatula root isoflavonoid accumulation.
AB  - Cadmium is a serious environmental pollution threats to the planet. Its
      accumulation in plants affects many cellular functions, resulting in growth and
      development inhibition, whose mechanisms are not fully understood. However, some
      fungi forming arbuscular mycorrhizal symbiosis with the majority of plant species
      have the capacity to buffer the deleterious effect of this heavy metal. In the
      present work we investigated the capacity of Rhizophagus irregularis (syn. Glomus
      irregularis) to alleviate cadmium stress in Medicago truncatula. In spite of a
      reduction in all mycorrhizal parameters, plants colonized for 21 days by R.
      irregularis and treated by 2 mg kg-1 cadmium displayed less growth inhibition in
      comparison to plants grown without cadmium. Cadmium strongly increased the
      accumulation of some isoflavonoids and their derivates: formononetin,
      malonylononin, medicarpin 3-O-beta-(6'-malonylglucoside), medicarpin and
      coumestrol. Interestingly, in plants colonized by R. irregularis we noticed a
      strong reduction of the cadmium-induced accumulation of root isoflavonoids, a
      part for medicarpin and coumestrol. Moreover, transcripts of chalcone reductase,
      a protein that we reported previously as being down-regulated in R. irregularis
      colonized M. truncatula roots, revealed a similar expression pattern with a
      strong increase in response to cadmium and a reduced expression in cadmium
      treated mycorrhizal roots.

PMID- 23000818
TI  - Molecular phylogeny of Cissus L. of Vitaceae (the grape family) and evolution of
      its pantropical intercontinental disjunctions.
AB  - Pantropical intercontinental disjunct distribution is a major biogeographic
      pattern in plants, and has been explained mainly by boreotropical migration via
      the North Atlantic land bridges (NALB) and transoceanic long-distance dispersal
      (LDD), and sometimes by vicariance. However, well-resolved phylogenies of
      pantropical clades are still relatively few. Cissus is the largest genus of the
      grape family Vitaceae and shows a pantropical intercontinental disjunction with
      its 300 species distributed in all major tropical regions. This study constructed
      the phylogenetic relationships and biogeographic diversification history of
      Cissus, employing five plastid markers (rps16, trnL-F, atpB-rbcL, trnH-psbA and
      trnC-petN). The results confirmed that Cissus polyphyletic, consisting of three
      main clades: the core Cissus, the Cissus striata complex, and the Australian
      Neotropical disjunct Cissus antarctica -C. trianae clade. The latter two clades
      need to be removed from Cissus to maintain the monophyly of the genus. The core
      Cissus is inferred to have originated in Africa and is estimated to have diverged
      from its relatives in Vitaceae in the late Cretaceous. It diversified in Africa
      into several main lineages in the late Paleocene to the early Eocene, colonized
      Asia at least three times in the Miocene, and the Neotropics in the middle
      Eocene. The NALB seems the most plausible route for the core Cissus migration
      from Africa to the Neotropics in the middle Eocene. Three African-Asian and two
      Neotropical-Australian disjunctions in Cissus s.l. are estimated to have
      originated in the Miocene and may be best explained by LDD.

PMID- 23000817
TI  - Empirical evaluation of partitioning schemes for phylogenetic analyses of
      mitogenomic data: an avian case study.
AB  - Whole mitochondrial genome sequences have been used in studies of animal
      phylogeny for two decades, and current technologies make them ever more
      available, but methods for their analysis are lagging and best practices have not
      been established. Most studies ignore variation in base composition and
      evolutionary rate within the mitogenome that can bias phylogenetic inference, or
      attempt to avoid it by excluding parts of the mitogenome from analysis. In
      contrast, partitioned analyses accommodate heterogeneity, without discarding
      data, by applying separate evolutionary models to differing portions of the
      mitogenome. To facilitate use of complete mitogenomic sequences in phylogenetics,
      we (1) suggest a set of categories for dividing mitogenomic datasets into
      subsets, (2) explore differences in evolutionary dynamics among those subsets,
      and (3) apply a method for combining data subsets with similar properties to
      produce effective and efficient partitioning schemes. We demonstrate these
      procedures with a case study, using the mitogenomes of species in the grackles
      and allies clade of New World blackbirds (Icteridae). We found that the most
      useful categories for partitioning were codon position, RNA secondary structure
      pairing, and the coding/noncoding distinction, and that a scheme with nine data
      groups outperformed all of the more complex alternatives (up to 44 data groups)
      that we tested. As hoped, we found that analyses using whole mitogenomic
      sequences yielded much better-resolved and more strongly-supported hypotheses of
      the phylogenetic history of that locus than did a conventional 2-kilobase sample
      (i.e. sequences of the cytochrome b and ND2 genes). Mitogenomes have much
      untapped potential for phylogenetics, especially of birds, a taxon for which they
      have been little exploited except in investigations of ordinal-level
      relationships.

PMID- 23000819
TI  - Next-generation phylogenomics using a Target Restricted Assembly Method.
AB  - Next-generation sequencing technologies are revolutionizing the field of
      phylogenetics by making available genome scale data for a fraction of the cost of
      traditional targeted sequencing. One challenge will be to make use of these
      genomic level data without necessarily resorting to full-scale genome assembly
      and annotation, which is often time and labor intensive. Here we describe a
      technique, the Target Restricted Assembly Method (TRAM), in which the typical
      process of genome assembly and annotation is in essence reversed. Protein
      sequences of phylogenetically useful genes from a species within the group of
      interest are used as targets in tblastn searches of a data set from a lane of
      Illumina reads for a related species. Resulting blast hits are then assembled
      locally into contigs and these contigs are then aligned against the reference
      "cDNA" sequence to remove portions of the sequences that include introns. We
      illustrate the Target Restricted Assembly Method using genomic scale datasets for
      20 species of lice (Insecta: Psocodea) to produce a test phylogenetic data set of
      10 nuclear protein coding gene sequences. Given the advantages of using DNA
      instead of RNA, this technique is very cost effective and feasible given current
      technologies.

PMID- 23000820
TI  - Systematics and evolutionary history of butterflies in the "Taygetis clade"
      (Nymphalidae: Satyrinae: Euptychiina): towards a better understanding of
      Neotropical biogeography.
AB  - The so-called "Taygetis clade" is a group of exclusively Neotropical butterflies
      classified within Euptychiina, one of the largest subtribes in the subfamily
      Satyrinae. Since the distribution of the ten genera belonging to this group
      ranges throughout the entire Neotropics, from lowlands to lower montane habitats,
      it offers a remarkable opportunity to study the region's biogeographic history as
      well as different scenarios for speciation in upland areas. We inferred a robust
      and well-sampled phylogeny using DNA sequences from four genes (4035 bp in total)
      using maximum parsimony and Bayesian inference. We estimated divergence times
      using the Bayesian relaxed clock method calibrated with node ages from previous
      studies. Ancestral ranges of distribution were estimated using the dispersal
      extinction-cladogenesis (DEC) model as implemented in the program Lagrange. We
      propose several taxonomic changes and recognize nine well-supported natural
      genera within the "Taygetis clade": Forsterinaria (subsuming Guaianaza syn.
      nov.), Parataygetis, Posttaygetis, Harjesia (excluding Harjesia griseola and
      Harjesia oreba), Pseudodebis (including Taygetomorpha syn. nov.,), Taygetina
      (subsuming Coeruleotaygetis syn. nov., Harjesia oreba comb. nov., Taygetis
      weymeri comb. nov. and Taygetis kerea comb. nov.), Taygetis (excluding Taygetis
      ypthima, Taygetis rectifascia, Taygetis kerea and Taygetis weymeri), and two new
      genera, one containing Harjesia griseola, and the other Taygetis ypthima and
      Taygetis rectifascia. The group diversified mainly during late Miocene to
      Pliocene, coinciding with the period of drastic changes in landscape
      configuration in the Neotropics. Major dispersals inferred from the Amazon basin
      towards northwestern South America, the Atlantic forests and the eastern slope of
      the Andes have mostly shaped the evolution and diversification of the group.
      Furthermore, expansion of larval dietary repertoire might have aided net
      diversification in the two largest genera in the clade, Forsterinaria and
      Taygetis.

PMID- 23000821
TI  - Simple and inexpensive incorporation of 19F-tryptophan for protein NMR
      spectroscopy.
AB  - Fluorine-containing amino acids are valuable probes for the biophysical
      characterization of proteins. Current methods for (19)F-labeled protein
      production involve time-consuming genetic manipulation, compromised expression
      systems and expensive reagents. We show that Escherichia coli BL21, the workhorse
      of protein production, can utilise fluoroindole for the biosynthesis of proteins
      containing (19)F-tryptophan.

PMID- 23000822
TI  - Occupational trichloroethylene exposure and kidney cancer risk: a meta-analysis.
AB  - OBJECTIVES: Inconsistent epidemiological findings, debate over interpretation,
      and extrapolation of findings from animal studies to humans have produced
      uncertainty surrounding the carcinogenicity of trichloroethylene (TCE) exposure
      in occupational settings. We updated meta-analyses of published case-control and
      cohort studies exploring occupational TCE exposure and kidney cancer risk,
      incorporating new analytical results from three recently published cohort studies
      and a case-control study. METHODS: PubMed MEDLINE was searched for studies
      published from 1950 to 2011 assessing occupational exposure to chlorinated
      solvents, degreasers or TCE. All cohort (N=15) and case-control (N=13) studies
      included in analyses were stratified by assessment of occupational exposure to
      TCE specifically and to any chlorinated solvent. RESULTS: Significantly elevated
      summary estimates were observed for cohort studies (relative risk (RR) 1.26, 95%
      CI 1.02 to 1.56; p heterogeneity=0.65), case-control studies (OR 1.35, 95% CI
      1.17 to 1.57; p heterogeneity=0.41), and cohort and case-control studies combined
      (RR 1.32, 95% CI 1.17 to 1.50, p heterogeneity=0.63) that specifically assessed
      TCE exposure after excluding outlier studies that contributed to heterogeneity.
      Non-significantly elevated summary estimates were generally observed for studies
      of workers exposed to chlorinated solvents but who were not assessed for TCE
      specifically. CONCLUSIONS: Regardless of study design, significant and stronger
      estimates were only observed in studies specifically assessing occupational
      exposure to TCE. Estimates were lower in studies assessing occupational exposure
      to chlorinated solvents. This updated meta-analysis supports an association
      between occupational TCE exposure and kidney cancer and provides evidence that
      exposure misclassification may weaken estimates assessing exposure to the broader
      class of chlorinated solvents.

PMID- 23000823
TI  - Employment and occupational outcomes of workers with musculoskeletal pain in a
      French region.
AB  - OBJECTIVES: To study the employment and occupational outcomes of workers who were
      diagnosed with upper limb musculoskeletal disorders (UL-MSDs) or had complained
      of upper limb musculoskeletal pain a few years before compared with workers who
      had no upper limb pain. METHODS: In 2002-2005, an epidemiological surveillance
      system was set up. Occupational physicians examined 3710 randomly selected
      workers. It focused on six UL-MSDs: rotator cuff syndrome, lateral epicondylitis,
      flexor-extensor peritendinitis of the hands and fingers, de Quervain's disease,
      carpal tunnel syndrome and ulnar tunnel syndrome. Three groups were constituted:
      a 'UL-MSD' group (workers with a clinically diagnosed UL-MSD at baseline, 13% of
      the cohort); a 'PAIN' group (workers with pain in the previous 7 days at baseline
      and without any clinically diagnosed form, 38%); and a 'HEALTHY' group (workers
      with no disorder or upper limb pain in the previous 7 days, 49%). They completed
      a questionnaire between 2007 and 2009. RESULTS: A total of 2332 responded. Fewer
      subjects were still in work in the 'UL-MSD' group (79.3%) than in the 'PAIN'
      (85.9%) and 'HEALTHY' (90.4%) groups, the difference remaining significant after
      adjusting for gender, age, occupational category, type of company and
      comorbidities. Of the subjects still in work, 24% had changed their work station
      in the same company in the 'PAIN' group compared with 19% in the 'HEALTHY' group
      and 21% in the 'UL-MSD' group. CONCLUSIONS: This study showed the impact of
      musculoskeletal pain on employment outcome and the difficulty of keeping workers
      with musculoskeletal problems at work.

PMID- 23000824
TI  - A comparison of occupational and non-occupational exposure to diesel exhausts and
      its consequences for studying health effects.

PMID- 23000825
TI  - Chronic obstructive pulmonary disease and longitudinal changes in pulmonary
      function due to occupational exposure to respirable quartz.
AB  - OBJECTIVES: The present study sought to examine the long-term effects of exposure
      to respirable quartz on pulmonary function with particular focus on chronic
      obstructive pulmonary disease (COPD). METHODS: The study is based on the Wismut
      cohort of former uranium miners. Spirometric data were ascertained together with
      quantitative estimates of cumulative exposure to respirable quartz for each of
      1421 study subjects born between 1954 and 1956. The case definition for COPD is
      based on the criteria of the Global Initiative for Chronic Obstructive Lung
      Disease. Linear mixed regression models were fitted to identify significant
      determinants of longitudinal changes in lung function parameters. RESULTS: An
      average of five spirometries were available for each miner. It was shown that
      cumulative exposure to 1 mg/m(3)-year respirable quartz leads, on average, to a
      relative reduction in forced expiratory volume in 1 s/ orced vital capacity
      (FEV(1)/FVC) of 2.75% (p<0.001). A nested case-control approach demonstrated that
      the risk for COPD stage I increases with increasing cumulative exposure to
      respirable quartz (OR 1.81 per 1 mg/m(3)-year). CONCLUSIONS: This paper adds
      further evidence on the long-term effects of exposure to respirable quartz, which
      include a decline in pulmonary function parameters and an increase in the
      incidence of COPD.

PMID- 23000826
TI  - Occupational risk factors associated with work-exacerbated asthma in Quebec.
AB  - BACKGROUND: There is limited information regarding the occupational exposures of
      subjects with a diagnosis of work-exacerbated asthma (WEA). OBJECTIVES: To: (1)
      identify potential specific occupational, chemical, biological and physical
      agents associated with incident cases of WEA and (2) compare these agents with
      occupational exposures of occupational asthma (OA) and non-work-related asthma
      (NWRA) cases. METHODS: Subjects were workers with work-related asthma (WRA) or
      NWRA referred between 2005 and 2008 to two Quebec clinics specialised in the
      field of WRA. Specific inhalation challenges were performed to differentiate OA
      from WEA. Work exposures were assessed using a detailed occupational
      questionnaire. Exposures to 41 chemical and biological agents were coded in a
      semiquantitative way according to a combination of indices for concentration in
      workplace air, frequency and confidence of exposure by an occupational hygienist
      expert in occupational exposure coding. This expert was blind to the medical
      status of WEA, OA or NWRA. Five physical agents were coded on a yes/no scale.
      RESULTS: 153 subjects were enrolled (53 WEA, 67 OA and 33 NWRA). WEA cases were
      significantly more exposed to ammonia, engine exhaust fumes, silica, mineral
      fibres, aerosol propellants and solvents, and significantly less exposed to
      animal derived dust and enzymes than were OA cases. Exposure to physical
      conditions did not differ between WEA and OA. CONCLUSIONS: Exposures associated
      with WEA differ from those associated with OA in this study. A proportion of
      subjects with WEA may suffer from low-dose irritant asthma, which remains a
      hypothesis to be tested.

PMID- 23000827
TI  - Risk of leukaemia mortality from exposure to ionising radiation in US nuclear
      workers: a pooled case-control study.
AB  - OBJECTIVE: To follow-up on earlier studies of the leukaemogenicity of
      occupational ionising radiation exposure. METHODS: We conducted a nested case
      control analysis of leukaemia mortality in a pooled cohort of US nuclear workers
      followed through 2005. Each case was matched to four controls on attained age.
      Exposures were estimated from available records. General relative risk models
      were used to estimate the excess relative risk (ERR) of leukaemia, excluding
      chronic lymphocytic (CLL), acute myeloid leukaemia, chronic myeloid leukaemia and
      CLL while controlling for potential confounders. Preferred exposure lags and time
      windows of risks were calculated using joint maximum likelihood. Dose-response
      was also examined using linear, linear-quadratic, categorical and restricted
      cubic spline models. RESULTS: There were 369 leukaemia deaths in 105 245 US
      nuclear workers. The adjusted ERR for non-CLL leukaemia was 0.09 (95% CI -0.17 to
      0.65) per 100 mGy. Elevated non-CLL risks were observed from exposures occurring
      6-14 years prior to attained age of cases (ERR per 100 mGy=1.9; 95% CI <0 to
      8.0). Lagged models indicated non-linearity of risk at very low (<10 mGy) and
      high (>100 mGy) doses, which contributed to the imprecision of results in linear
      models. Similar risk attenuation was not evident in time-windows-based models.
      CONCLUSIONS: Risk estimates were in reasonable agreement with previous estimates,
      with the temporality of non-CLL leukaemia risk as a dominant factor in dose
      response analyses. Future research should focus on methods that improve
      evaluations of the dose-response, particularly in the low-dose range.

PMID- 23000828
TI  - Enhanced PCBs sorption on biochars as affected by environmental factors: Humic
      acid and metal cations.
AB  - Biochar plays an important role in the behaviors of organic pollutants in the
      soil environment. The role of humic acid (HA) and metal cations on the adsorption
      affinity of polychlorinated biphenyls (PCBs) to the biochars in an aqueous medium
      and an extracted solution from a PCBs-contaminated soil was studied using batch
      experiments. Biochars were produced with pine needles and wheat straw at 350 
      degrees C and 550  degrees C under anaerobic condition. The results showed that
      the biochars had high adsorption affinity for PCBs. Pine needle chars adsorbed
      less nonplanar PCBs than planar ones due to dispersive interactions and
      separation. Coexistence of HA and metal cations increased PCBs sorption on the
      biochars accounted for HA adsorption and cation complexation. The results will
      aid in a better understanding of biochar sorption mechanism of contaminants in
      the environment.

PMID- 23000829
TI  - A systematic review and meta-analysis of pretherapeutic lymph node staging of
      colorectal cancer by 18F-FDG PET or PET/CT.
AB  - The purpose of the present study was to conduct a systematic review and meta
      analysis of the published literature to evaluate the diagnostic performance of
      fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) PET in the pretherapeutic
      assessment of nodal staging in patients with colorectal cancer (CRC). We
      conducted a systematic MEDLINE search of articles in the published literature
      (last update, February 2012). Two reviewers independently assessed the
      methodological quality of each study. We estimated pooled sensitivity,
      specificity, summary receiver operating characteristic curves, and summary
      likelihood ratios. A total of 409 patients from 10 studies were analyzed. The
      pooled estimates of sensitivity, specificity, positive likelihood ratio, and
      negative likelihood ratio of 18F-FDG PET [PET/computed tomography (CT)] in the
      detection of pretherapeutic lymph node involvement in patients with CRC were
      42.9% [95% confidence interval (CI): 36.0-50.0%], 87.9% (95% CI: 82.6-92.0%),
      2.82 (95% CI: 1.96-4.07), and 0.69 (95% CI: 0.62-0.78), respectively. There is no
      solid evidence to support the routine clinical application of 18F-FDG PET
      (PET/CT) in the pretherapeutic evaluation of lymph node status in patients with
      CRC. However, 18F-FDG PET (PET/CT) could be used to strengthen the possibility of
      suspected metastatic lymph nodes detected by other imaging modalities.

PMID- 23000830
TI  - TLR4 is a target of environmentally relevant concentration of lead.
AB  - Lead (Pb) alters the susceptibility to different pathogens suggesting that
      macrophage-mediated defense mechanisms, through activation of toll-like receptors
      (TLRs), may be affected by Pb. The aim of this study was to test whether
      activation of TLR4 is a targeted molecule to the effect of environmentally
      relevant Pb concentrations (0.05, 0.5 and 5MUg/dL). The function of macrophages
      activated through TLR4 was evaluated using as TLR4 ligand lipopolysaccharides
      (LPSs) from two different pathogens: Escherichia coli and Salmonella typhimurium.
      Pb induced proliferation, increased the NO(-) baseline, IL-1beta and IL-6
      secretion. Interestingly, Pb exposure induced differential effects on cells
      stimulated with the two LPS used: in macrophages stimulated with LPS from E.
      coli, Pb caused an early decrease in proliferation, increase NO(-) production,
      and decrease IL-6 and TNF-alpha secretion; in macrophages stimulated with LPS
      from S. typhimurium, Pb decreased proliferation after 36h, induced a biphasic
      effect on NO(-) production, and enhance the secretion of IL-1beta, IL-6 and TNF
      alpha. Results suggest that TLR4 is a target for the Pb effect, which up to
      5.0MUg/dL affect immune competence against pathogens, dependent on the bacterial
      species. This effect may be attributable to structural differences that determine
      LPS affinity for TLR4.

PMID- 23000831
TI  - Natural scene stimuli and lapses of sustained attention.
AB  - We conducted two experiments using naturalistic scene stimuli to test the
      resource theory and mindlessness theory of sustained attention. In experiment 1,
      28 participants completed a traditional formatted vigilance task consisting of
      non-repeating forest or urban picture stimuli as target stimuli. Participants
      filled out pre- and post-task assessments of arousal and conscious thoughts.
      There was still a vigilance decrement, despite non-repetitive, natural target
      stimuli. Participants found the task demanding and were actively engaged in the
      task. In experiment 2, 25 participants completed a Sustained Attention to
      Response Task (SART) using the stimuli from experiment 1. Participants performed
      significantly worse on this SART than either brain injury patients or controls
      performing equivalent numeric stimuli SARTs have in previous studies.
      Participants thought the task was demanding and they were actively engaged with
      the task. Overall, the results of both studies support a resource theory of
      sustained attention lapses, not a mindlessness theory.

PMID- 23000832
TI  - Molecular interactions of penetration enhancers within ceramides organization: a
      Raman spectroscopy approach.
AB  - Skin penetration enhancers (PEs) are present in a large number of dermatological
      and cosmetic products to aid absorption of curatives and aesthetics. They
      penetrate into skin to reversibly decrease the barrier resistance. Their mode of
      action on the stratum corneum lipids involves interactions at the level of the
      polar heads of the lipids and at the level of apolar hydrophobic alkyl chains.
      Vibrational spectroscopies have been widely used for the study of intra- and
      intermolecular structures of long chain compounds. In this work we employ Raman
      spectroscopy to probe the local activities on ceramides and to monitor the
      dependence of this activity on the ceramide structure, i.e. the presence of
      double bonds in the alkyl chains, the length of these chains and the nature of
      the polar heads. The action of three PEs, limonene, DMSO and ethanol, is studied.
      For intra-chain monitoring, the Raman features associated with CH(3) rocking (450
      890 cm(-1)) and CC stretching (1050-1140 cm(-1)) are used while the lateral
      packing is observed with the CH(2) stretching band evolution (2840-2900 cm(-1)).
      Finally, polar interactions are probed using the Amide I band (1600-1650 cm(-1)).

PMID- 23000834
TI  - Successful double umbilical cord blood transplantation for relapsed juvenile
      myelomonocytic leukemia.

PMID- 23000835
TI  - "Too good to be true": the controversy over the use of permanganate of potash as
      an antidote to snake poison and the circulation of Brazilian physiology in the
      nineteenth century.
AB  - This article examines an international controversy over the most visible
      scientific event of Brazilian physiology in the nineteenth century. In 1881,
      Brazilian scientist Joao Baptista Lacerda stated that he had found an efficient
      antidote to the poison of Brazilian snakes: permanganate of potash (nowadays,
      potassium permanganate). His findings were given great publicity in Brazil and
      traveled rapidly around the world. Scientists, especially in France, contradicted
      Lacerda's claims. They argued that permanganate of potash could not be a genuine
      antidote to snake bites since it could not neutralize snake venom when diffused
      in the body. Lacerda turned down such criticism, claiming that clinical
      observation provided solid evidence for the drug's local action, on the spot
      surrounding the bite. The controversy over the use of permanganate of potash as
      an antidote to snake bite illustrates different regimes of proof that could be
      mobilized in favor of a physiological discovery.

PMID- 23000836
TI  - African American southerners and white physicians: medical care at the turn of
      the twentieth century.
AB  - Much of what scholars know about race and medicine in the late-nineteenth-and
      early-twentieth-century South relates to the racial beliefs of white physicians
      and the segregated and exploitative treatment of black patients in hospitals and
      public health programs. This article shifts scholarly attention to the ways
      African American patients and their families took part in medical practice in
      commonplace settings of the home and office. The author examines how African
      Americans called upon local physicians in the rural and small-town South, how
      white physicians responded, and how they interacted in cases of serious illness,
      injury, and surgery. The claims of black southerners to physicians' treatments,
      in combination with small-town physicians' continuing reliance on interpersonal
      practices of medical care, made for an erratic but potentially distinctive cross
      racial encounter-one involving a greater degree of negotiated authority and
      personal care than what generally has been recognized for this time and place.

PMID- 23000837
TI  - Eugenics visualized: the exhibit of the Third International Congress of Eugenics,
      1932.
AB  - SUMMARY: This article investigates the exhibit of the Third     International
      Congress of Eugenics, which was organized by Harry     Hamilton Laughlin and
      showcased at the American Museum of Natural     History in 1932. It argues that
      the exhibit's displays shaped popular     eugenic ideology by connecting
      particular eugenic principles to     specific visual representations that were
      experienced in relation to     binaries such as the artistically traditional and
      the modern, the     classical and the grotesque, and the scientific and the
      spectacle (or     the "freak" and the medical specimen). These dichotomies were,
      in turn,     experienced within the context of the exhibit's overall theme of    
      eugenics as anchored in the past and the future and concern over the    
      differential birthrate. The exhibit to the Third Congress provides     insight
      into growing tensions within the eugenics movement of the     1930s, the
      importance of positive eugenics, the aesthetics of heredity,     and how the
      "scientific truths" of a given era are publicized and     perpetuated.

PMID- 23000838
TI  - "Life in a germ-free world": isolating life from the laboratory animal to the
      bubble boy.
AB  - This article examines a specific technology, the germ-free "isolator," tracing
      its development across three sites: (1) the laboratory for the production of
      standard laboratory animals, (2) agriculture for the efficient production of farm
      animals, and (3) the hospital for the control and prevention of cross-infection
      and the protection of individuals from infection. Germ-free technology traveled
      across the laboratory sciences, clinical and veterinary medicine, and industry,
      yet failed to become institutionalized outside the laboratory. That germ-free
      technology worked was not at issue. Working, however, was not enough. Examining
      the history of a technology that failed to find widespread application reveals
      the labor involved in aligning cultural, societal, and material factors necessary
      for successful medical innovation.

PMID- 23000841
TI  - Drug nanocrystals in the commercial pharmaceutical development process.
AB  - Nanosizing is one of the most important drug delivery platform approaches for the
      commercial development of poorly soluble drug molecules. The research efforts of
      many industrial and academic groups have resulted in various particle size
      reduction techniques. From an industrial point of view, the two most advanced top
      down processes used at the commercial scale are wet ball milling and high
      pressure homogenization. Initial issues such as abrasion, long milling times and
      other downstream-processing challenges have been solved. With the better
      understanding of the biopharmaceutical aspects of poorly water-soluble drugs, the
      in vivo success rate for drug nanocrystals has become more apparent. The clinical
      effectiveness of nanocrystals is proven by the fact that there are currently six
      FDA approved nanocrystal products on the market. Alternative approaches such as
      bottom-up processes or combination technologies have also gained considerable
      interest. Due to the versatility of nanosizing technology at the milligram scale
      up to production scale, nanosuspensions are currently used at all stages of
      commercial drug development, Today, all major pharmaceutical companies have
      realized the potential of drug nanocrystals and included this universal
      formulation approach into their decision trees.

PMID- 23000842
TI  - Potential pitfalls with the use of acetoxy (CH(3)COO) drugs in studies on nitric
      oxide synthase in platelets.

PMID- 23000843
TI  - In situ synthesis of 3D flower-like NiMnFe mixed oxides as monolith catalysts for
      selective catalytic reduction of NO with NH3.
AB  - Novel 3D flower-like NiMnFe mixed oxides as monolith catalysts prepared by an in
      situ hydrothermal method show enhanced performance for the selective catalytic
      reduction of NO with NH(3).

PMID- 23000845
TI  - Both early and late changes in psychological variables relate to treatment
      outcome for musculoskeletal pain patients at risk for disability.
AB  - We know little about why some people get better after psychological treatments
      for pain disability, whereas other people do not. In order to understand
      differences in treatment response, we need to explore processes of change during
      treatment. It has been suggested that people with pain complaints who change
      early in treatment have better outcomes. Therefore, we aimed to investigate
      whether changes in psychological variables at different time points are related
      to outcome, and whether early or late changes are better predictors of outcome.
      We used the fear avoidance model as a theoretical framework. We followed 64
      patients weekly over 6-7 weeks and then determined outcome. Our findings indicate
      that people who decrease in catastrophizing and function early in treatment as
      well as in depressive symptoms, worry, fear avoidance beliefs and function late
      in treatment have better outcomes. Early decreases in function, and late
      decreases in depressive symptoms and worry uniquely predict improvements in
      disability. While early and late changes covaried concurrently, there were no
      significant sequential relationships between early and late changes. Changes in
      the proposed process variables in the fear avoidance model, early as well as late
      in treatment, thus add valuable information to the explanation of outcome.

PMID- 23000846
TI  - Safety behavior can hamper the extinction of fear of movement-related pain: an
      experimental investigation in healthy participants.
AB  - Excessive fear of movement-related pain (FMRP), and its associated avoidance
      behavior, is considered a major risk factor for disability in chronic
      musculoskeletal pain. The current study aimed to investigate whether engaging in
      safety behavior, conceptualized as an avoidance response, hampers the extinction
      of FMRP. In a differential conditioning paradigm, we used joystick movements as
      conditioned stimuli (CSs) and a painful electrocutaneous stimulus as the
      unconditioned stimulus (US). In the Safety group, participants received the
      opportunity to avoid the pain-US by pressing a safety button during the
      extinction phase, whereas in the Control group, this option was not included. In
      a subsequent test phase, this safety button was no longer available. In two
      experiments, results demonstrate successful acquisition and extinction.
      Retrospective FMRP ratings in both experiments revealed a return of fear of pain
      in the test phase in the Safety group, but not in the Control group. In
      Experiment 1, mean eyeblink startle reflex amplitudes partly corroborated the
      self-report findings on fear of pain. The present results suggest that performing
      safety behavior during cognitive-behavioral interventions, i.e., exposure, might
      increase the risk of a return of FMRP.

PMID- 23000847
TI  - Sheathless capillary electrophoresis-mass spectrometry with a high-sensitivity
      porous sprayer for cationic metabolome analysis.
AB  - Sheath-flow capillary electrophoresis-mass spectrometry (CE-MS) has emerged as a
      new tool for comprehensive analysis of charged metabolites. However, it needs to
      be more sensitive. Here, we report a sheathless capillary electrophoresis
      electrospray ionization-mass spectrometry method for cationic metabolome
      analysis. This system used a high-sensitivity porous sprayer interface and 10%
      (v/v) acetic acid as the background electrolyte (BGE). Under optimized
      conditions, 53 cationic metabolites, including amino acids and their derivatives,
      amines, nucleic acids and small peptides, were successfully separated and
      selectively detected with a time-of-flight mass spectrometer. At a signal-to
      noise ratio of three, the concentration detection limits for these compounds were
      between 0.004 and 0.8 MUmol L(-1) (amount detection limit, 0.01 to 2 fmol) with
      pressure injection at 20.7 kPa for 5 s (2.6 nL). Compared with conventional
      sheath-flow CE-MS, the detection limit of the present method was increased more
      than 5-fold for 21 (40%) of the compounds detected. When the method was applied
      to the analysis of cationic metabolites obtained from human urine, there was a 10
      fold increase in the number of detected peaks compared with conventional methods.
      More than 180 successive runs could be conducted without any problems, and only
      the BGE needed to be changed.

PMID- 23000848
TI  - Optical imaging of kidney cancer with novel near infrared heptamethine
      carbocyanine fluorescent dyes.
AB  - PURPOSE: We assessed the application of near infrared heptamethine carbocyanine
      dyes, including IR-783 and the synthetic analogue MHI-148, as optical imaging
      agents for the rapid detection of human kidney cancer. MATERIALS AND METHODS: The
      uptake, retention and subcellular localization of these organic dyes were
      investigated in cultured kidney cancer cells. Tumor specificity of dye uptake and
      retention was evaluated by whole body imaging of mice bearing human kidney cancer
      xenografts or freshly harvested clinical kidney cancer specimens. In addition,
      dye accumulation at the tissue and cellular levels was confirmed by ex vivo
      studies with results confirmed by fluorescence imaging of frozen tissue sections.
      Peripheral blood spiked with kidney cancer cells was stained to simulate the
      detection of circulating tumor cells. RESULTS: Preferential uptake and retention
      of carbocyanine near infrared dyes was observed in cultured human kidney cancer
      cells, human kidney cancer cell spiked whole blood, human kidney cancer
      xenografts and freshly harvested human kidney cancer tissues compared to normal
      kidney epithelial cells and normal host organs. CONCLUSIONS: We describe a new
      class of near infrared heptamethine carbocyanine dyes that show potential for
      detecting kidney cancer cells in circulating blood and kidney cancer cells in
      clinical specimens. Near infrared carbocyanine dyes can be further developed as
      dual modality agents for deep tissue imaging of localized and disseminated kidney
      cancer in patients.

PMID- 23000850
TI  - Jack: passing of the great mentor.

PMID- 23000849
TI  - Salvage robotic assisted laparoscopic radical prostatectomy: a single
      institution, 5-year experience.
AB  - PURPOSE: Salvage robotic assisted laparoscopic prostatectomy is a treatment
      option for certain patients with recurrent prostate cancer after primary therapy.
      Data regarding patient selection, complication rates and cancer outcomes are
      scarce. We report the largest, single institution series to date, to our
      knowledge, of salvage robotic assisted laparoscopic prostatectomy. MATERIALS AND
      METHODS: We reviewed our database of 4,234 patients treated with robotic assisted
      laparoscopic prostatectomy at Vanderbilt University and identified 34 men who had
      surgery after the failure of prior definitive ablative therapy. Each patient had
      biopsy proven recurrent prostate cancer and no evidence of metastases. The
      primary outcome measure was biochemical failure. RESULTS: Median time from
      primary therapy to salvage robotic assisted laparoscopic prostatectomy was 48.5
      months with a median preoperative prostate specific antigen of 3.86 ng/ml. Most
      patients had Gleason scores of 7 or greater on preoperative biopsy, although 12
      (35%) had Gleason 8 or greater disease. After a median followup of 16 months 18%
      of patients had biochemical failure. The positive margin rate was 26%, of which
      33% had biochemical failure after surgery. On univariable analysis there was a
      significant association between prostate specific antigen doubling time and
      biochemical failure (HR 0.77, 95% CI 0.60-0.99, p = 0.049) as well as between
      Gleason score at original diagnosis and biochemical failure (HR 3.49, 95% CI 1.18
      10.3, p = 0.023). There were 2 Clavien II-III complications, namely a pulmonary
      embolism and a rectal laceration. Postoperatively 39% of patients had excellent
      continence. CONCLUSIONS: Salvage robotic assisted laparoscopic prostatectomy is
      safe, with many favorable outcomes compared to open salvage radical prostatectomy
      series. Advantages include superior visualization of the posterior prostatic
      plane, modest blood loss, low complication rates and short length of stay.

PMID- 23000851
TI  - Atypical adenomatous hyperplasia (adenosis) of the prostate.

PMID- 23000853
TI  - Cystitis, pyelonephritis and perinephric abscess due to ureaplasma urealyticum.

PMID- 23000855
TI  - Sacral neuromodulation is an effective treatment for interstitial
      cystitis/bladder pain syndrome: pro.

PMID- 23000856
TI  - Nocturia, sleep disturbance and the metabolic syndrome.

PMID- 23000857
TI  - The volume outcome relationship in urology: moving the field forward.

PMID- 23000858
TI  - Sacral neuromodulation is an effective treatment for interstitial
      cystitis/bladder pain syndrome: con.

PMID- 23000860
TI  - Improvement by phytotherapeutic agent of detrusor overactivity, down-regulation
      of pharmacological receptors and urinary cytokines in rats with cyclophosphamide
      induced cystitis.
AB  - PURPOSE: We characterized pharmacological effects of the phytotherapeutic agent
      Eviprostat(r) on urodynamic parameters, bladder muscarinic and purinergic
      receptors, and urinary cytokines in rats with cyclophosphamide induced cystitis.
      MATERIALS AND METHODS: Urodynamic parameters in cyclophosphamide (150 mg/kg
      intraperitoneally) treated rats were measured by a cystometric method. Muscarinic
      and purinergic receptors in the bladder and other tissues were measured by
      radioreceptor assays using [N-methyl-(3)H]scopolamine methyl chloride and
      [(3)H]alphabeta-MeATP, respectively. The urinary cytokines interleukin-1beta, 6
      and 17 were measured with enzyme-linked immunoassay kits. Eviprostat (36 mg/kg
      per day twice daily for 7 days) was orally administered. RESULTS: On cystometry
      the micturition interval and micturition volume were significantly decreased in
      cyclophosphamide vs sham treated rats, while micturition frequency, basal
      pressure and post-void residual urine volume were significantly increased. Repeat
      oral administration of Eviprostat in cyclophosphamide treated rats significantly
      increased the micturition interval and micturition volume, and decreased
      micturition frequency, basal pressure and post-void residual urine volume. The
      maximal number of binding sites for [N-methyl-(3)H]scopolamine methyl chloride
      and [(3)H]alphabeta-MeATP was significantly decreased in the bladder of
      cyclophosphamide vs sham treated rats. Such decreases were significantly
      attenuated by repeat Eviprostat treatment. Increased urinary cytokine levels in
      cyclophosphamide treated rats were also effectively attenuated by Eviprostat.
      CONCLUSIONS: Repeat Eviprostat treatment significantly improved detrusor
      overactivity, down-regulated the expression of bladder pharmacological receptors
      and increased urinary cytokine levels in rats with cyclophosphamide induced
      cystitis. Therefore, Eviprostat may be a pharmacologically useful
      phytotherapeutic agent for cystitis.

PMID- 23000861
TI  - Pressure driven digital logic in PDMS based microfluidic devices fabricated by
      multilayer soft lithography.
AB  - Advances in microfluidics now allow an unprecedented level of parallelization and
      integration of biochemical reactions. However, one challenge still faced by the
      field has been the complexity and cost of the control hardware: one external
      pressure signal has been required for each independently actuated set of valves
      on chip. Using a simple post-modification to the multilayer soft lithography
      fabrication process, we present a new implementation of digital fluidic logic
      fully analogous to electronic logic with significant performance advances over
      the previous implementations. We demonstrate a novel normally closed static gain
      valve capable of modulating pressure signals in a fashion analogous to an
      electronic transistor. We utilize these valves to build complex fluidic logic
      circuits capable of arbitrary control of flows by processing binary input signals
      (pressure (1) and atmosphere (0)). We demonstrate logic gates and devices
      including NOT, NAND and NOR gates, bi-stable flip-flops, gated flip-flops
      (latches), oscillators, self-driven peristaltic pumps, delay flip-flops, and a 12
      bit shift register built using static gain valves. This fluidic logic shows
      cascade-ability, feedback, programmability, bi-stability, and autonomous control
      capability. This implementation of fluidic logic yields significantly smaller
      devices, higher clock rates, simple designs, easy fabrication, and integration
      into MSL microfluidics.

PMID- 23000863
TI  - JIDC and Latin America.

PMID- 23000862
TI  - The challenge of cardiovascular prevention in primary care: implications of a
      European observational study in 8928 patients at different risk levels.
AB  - BACKGROUND: Cardiovascular prevention can be provided to patients at different
      risk levels. The aim of this study was to compare the quality of cardiovascular
      prevention provided in European primary care between patients with diagnosed
      coronary heart disease (CHD) and individuals at high risk due to known risk
      factors but not labelled with a diagnosis of cardiovascular disease (CVD).
      Additionally, we aimed to identify individual and practice factors to predict
      risk factor control. METHODS: An international cross-sectional study was
      conducted in 10 European countries. Clinical record data were abstracted for
      quality indicators for 8928 patients in 10 countries and patient questionnaires
      were completed by 7846 patients in nine countries. Information about 320 general
      practices was assessed using practice questionnaires and interviews. Hierarchical
      multilevel modelling was used for analyses. RESULTS: Recording of risk factors
      and advice was higher in the CHD than in the high-risk group. Risk factor control
      was better in the CHD group: uncontrolled levels of blood pressure (34.2 vs.
      49.3%; p < 0.001), cholesterol (32.4 vs. 64.5%; p < 0.001). Predictors of risk
      factor control were medication adherence (RR 0.97; p = 0.007) and health-related
      quality of life (RR 0.86; p = 0.005). Being at high risk (RR 1.42; p < 0.001),
      being single (RR 1.12; p < 0.001), and having lower educational level (RR 1.09; p
      < 0.001) were associated with poorer risk factor control. Practice factors were
      not associated with outcomes. CONCLUSIONS: Strategies to improve guidelines
      adherence in cardiovascular prevention may be stronger focused on individuals at
      risk before CVD is diagnosed and require organizational and political support to
      reinforce general practices.

PMID- 23000864
TI  - Outcomes of treatment in 50 cases with spinal brucellosis in Babol, Northern
      Iran.
AB  - INTRODUCTION: Duration of treatment for brucellar spondylitis in endemic regions
      is controversial. This study describes the outcome of treatment in 50 cases of
      brucellar spondylitis in Iran. METHODOLOGY: From April 2001 to September 2010, we
      treated 20, 13, 11 and 6 cases with doxycycline plus rifampin (DR), streptomycin
      plus doxycycline plus rifampin (SDR), cotrimoxazole plus doxycycline plus
      rifampin (CDR), and gentamicin plus doxycycline plus rifampin (GDR),
      respectively. Gentamicin and streptomycin were administered for 14 days and the
      other agents for 3 months. When complete clinical response was not achieved,
      therapy was continued. All patients were followed for one year. The Kaplan Meier
      method and the log rank test were used to compare the duration of therapy between
      SDR plus GDR patients with those treated with CDR or DR. RESULTS: Eight (45%), 10
      (76.9%), 7 (63.3%) and 6 (100%) cases treated for three months were cured with
      DR, SDR, CDR and GDR, respectively. Nine (45%), 4 (36.4%) and two (22.2%) were
      cured after four months with DR, CDR and SDR, respectively. Mean duration of
      therapy in the SDR plus GDR, CDR and DR was 3.26 +/- 0.17, 3.36 +/- 0.15 and 3.9
      +/- 0.23 months, respectively (p=0.49 and p=0.015, respectively). Three cases
      with epidural or paravertebral abscesses recovered after six months. Relapse
      occurred in one (9.1%) and two (10%) cases treated with CDR and DR, respectively.
      CONCLUSIONS: Brucellar spondylitis could be treated using different combinations
      of antimicrobials especially with a regimen containing aminoglycoside for four
      months; patients with epidural or paravertebral abscesses require longer
      treatment times.

PMID- 23000865
TI  - Assessment of the impact of malaria on CD4+ T Cells and haemoglobin levels of HIV
      malaria co-infected patients.
AB  - INTRODUCTION: The human immunodeficiency virus (HIV) and malaria destroy
      important cells required for proper immunological and haematological functioning
      of the body. This research therefore aimed to assess the effect of malaria on
      CD4+ and haemoglobin (Hb) levels of HIV-malaria co-infected patients.
      METHODOLOGY: The study was performed by sampling 220 adult HIV patients on highly
      active anti retroviral therapy (HAART) who routinely visited the Tema General
      Hospital in Ghana. Blood samples were obtained for both blood film microscopy
      identification of malaria parasites and analysis using rapid diagnostic test
      kits. A BD Facscount Analyzer was used in the quantification of CD4+ levels.
      RESULTS: Of the 220 patients sampled, 34 (15.5%) were HIV-malaria co-infected,
      all of whom (34; 100%) had CD4+ counts below the normal range, while 23 (12.9%)
      of the HIV mono-infected patients had normal CD4+ counts. Almost all HIV-malaria
      co-infected patients (33; 97.1%) had low Hb levels, whereas 79 (42.5%) of the HIV
      mono-infected patients had normal Hb. Malaria infection strongly correlated
      positively and significantly with both low CD4+ count (chi2 = 0.828, P = 0.003)
      and Hb (chi2 = 0.817, P = 0.004) levels. CONCLUSION: Malaria co-infection with
      HIV decreases CD4+ T cells and Hb levels in patients. It is therefore recommended
      that HIV patients in malaria endemic areas should adhere to malaria preventive
      measures.

PMID- 23000866
TI  - Severity of Plasmodium vivax malaria in Karachi: a cross-sectional study.
AB  - INTRODUCTION: Plasmodium vivax malaria affects billions of people annually. This
      study aimed to note the presentations and complications and subsequently to
      identify the determinants of in-patient hospital care of P. vivax malaria
      patients presenting to a tertiary care hospital in Karachi, Pakistan. Severity of
      the shock was also assessed using a shock index. METHODOLOGY: This study
      descriptive cross-sectional study was conducted at the Emergency Department of
      Aga Khan University Hospital, Karachi. All adult patients with a positive P.
      vivax peripheral film and/or immunochromatography admitted through the department
      were studied during 2009. Data was entered and analyzed using SPSS version 16.
      Keeping the length of stay at a cut-off of 48 hours after admission, the
      independent Student-t test was applied. Level of significance was taken at 0.05.
      RESULTS: A total of 97 patients were included in the study. Fever was the most
      common presentation. A significant number of patients had nonspecific complaints,
      but tachycardia, altered mental status, and adult respiratory distress syndrome
      were important findings. Mean shock index was 1 (SD 0.26). Common reasons for
      admission were thrombocytopenia and dehydration. Some patients were admitted for
      more than 48 hours. Complications included pneumonia and bleeding requiring
      platelet transfusion. CONCLUSION: This study highlights that the debilitating
      impact of P. vivax malaria remains high. Although the effects of severe vivax
      malaria can be contained through aggressive resuscitation and specific therapy,
      sensitivity and awareness of this complicated course must be highlighted among
      caregivers.

PMID- 23000867
TI  - The distribution of allelic and genotypic frequencies of  N-Acetyltransferase-2
      variants in an Argentine population.
AB  - INTRODUCTION: Arylamine N-acetyltransferase-2 (NAT-2) is a key human enzyme in
      drug detoxification and elimination. Mutations in NAT-2 affect the activity of
      anti-tuberculosis drugs and result in three different phenotypes: rapid (RA),
      intermediate (IA) and slow acetylators (SA). METHODOLOGY: The allelic, genotypic
      and phenotypic frequencies of NAT-2 were studied in 185 patients from Buenos
      Aires by restriction fragment length polymorphism. RESULTS: The following allele
      frequencies were obtained: *4 = 29.9%, *5 = 37.0, *6 = 25.6%, *7 = 8% and *14 =
      1.3%. With regard to the phenotype, we observed that 53.6% of the population was
      SA, 35.7% was IA and 10.7% was RA. CONCLUSION: A high prevalence of SA might have
      an impact on anti-TB drug-induced hepatotoxicity.

PMID- 23000868
TI  - Serological trail of Brucella infection in an urban slum population in Brazil.
AB  - INTRODUCTION: Brucellosis is a re-emerging zoonosis with new cases reported each
      year in many Latin American countries, but it is mostly under-recognized. This
      study presents a serological investigation of infection with Brucella abortus and
      Brucella canis in a poor urban community in the city of Salvador, Brazil.
      METHODOLOGY: Human sera (n = 180) were randomly selected from 3,171 samples taken
      from healthy individuals during 2003-2004 and tested with C-ELISA for B. abortus
      and I-ELISA for B. canis. RESULTS: Thirteen percent (24/180) of the individuals
      were positive for B. abortus and 4.6 % (8/174) were positive for B. canis. Among
      the variables studied only age (older than 45 years) appeared to be a risk factor
      for the detection of Brucella antibodies. CONCLUSION: These results indicate the
      presence of Brucella infection in this settlement and highlight the need to
      understand the epidemiology of infection under these circumstances to establish
      the necessary measures for surveillance and control.

PMID- 23000869
TI  - Reproductive tract infections (RTIs) among married non-pregnant women living in a
      low-income suburb of Beirut, Lebanon.
AB  - INTRODUCTION: This study aimed to identify reproductive tract infections (RTIs)
      in married, non-pregnant women, aged 18 to 49 years, living in a low-income
      suburb of Beirut, and to investigate the relationship between demographic and
      socioeconomic factors and these infections. METHODOLOGY: Among 1,015 women
      recruited for the study, 502 were found eligible and 441 were medically examined.
      Appropriate specimens were collected for Nisseria gonorrhea, Chlamydia
      trachomatis, Trichomonas vaginalis, candidiasis, and bacterial vaginosis.
      RESULTS: The results showed a relatively high prevalence of RTIs (28.2%). The
      prevalence rates of different agents were as follows: 22.9% of the women were
      positive for T. vaginalis, 8.8% for candidiasis, 4.5% for bacterial vaginosis,
      and 1% for N. gonorrhea; none of the women were positive for C. trachomatis.
      Regression analysis showed that women between the ages of 30 and 39 were twice
      more likely to have T. vaginalis as compared to younger women. Furthermore, women
      whose husbands were taxi drivers were at higher risk of acquiring T. vaginalis
      (OR = 2.2) as compared with women whose husbands occupation was listed as
      skilled/unskilled. This conclusion can be drawn for the odds of developing any
      RTI (OR = 2.15). Moreover, those participants with the lowest income were twice
      as likely to have any RTI compared to those with higher incomes. CONCLUSIONS:
      This study shows a relatively high prevalence of RTIs (T. vaginalis mainly). It
      urges further in-depth research on cultural practices and economic factors to
      understand the pattern of sexual behavior in this community.

PMID- 23000870
TI  - An approach to histology-based diagnosis and treatment of Madura foot.
AB  - Madura foot is a deep mycosis commonly seen in tropical and subtropical countries
      such as India. Its incidence is likely to rise in temperate regions as well, due
      to the increase in worldwide travel. The cases presented here are all
      agricultural workers from a rural part of northern India who had induration,
      fibrosis and minimal discharge from sinuses over the foot. Although culture
      remains the gold standard diagnostic test, this case report highlights the
      importance of histopathology in the early diagnosis and differentiation of common
      causative agents in Madura foot as repeated cultures are sometimes negative. Thus
      for mycetomas in which causative infectious agents cannot be isolated, histology
      may prove beneficial by avoiding inadvertent use of combined antifungal and
      antimicrobial agents so that a correct therapeutic modality can be decided,
      prognostic outcome be explained to the patient, and a preventable cause of
      deformity and disability can be identified and treated at an early stage.

PMID- 23000871
TI  - Understanding pathogens in the era of next generation sequencing.
AB  - What is a pathogen? Medical textbooks usually define a pathogen as any
      microorganism that causes disease. However, this widespread definition is
      problematic on a number of counts [1, 11]. Moreover, a generally accepted
      definition is not forthcoming among medical microbiologists, immunologists, and
      physicians. Here it is argued that there is another, and more pressing question
      to be asked, namely: what makes some organisms pathogenic and others not? Asking
      these questions instead allows for distinguishing pathogens from non-pathogens in
      a more flexible way, while at the same time emphasizing the roles of ecological
      and evolutionary processes in determining pathogenicity in infectious diseases.

PMID- 23000872
TI  - The standard of care: A moving target.

PMID- 23000873
TI  - The effect of expanding access to health insurance on the health and mortality of
      Social Security Disability Insurance beneficiaries.
AB  - We use a social experiment to estimate the impact of expanding health insurance
      coverage on the health and mortality of newly entitled SSDI beneficiaries who
      lacked health insurance. Our intent-to-treat estimates show that expanding health
      insurance has significant effects on self-reported health at one year following
      health insurance enrollment, positive effects on mental health and physical
      health at one year following health insurance enrollment, and no significant
      effects on mortality within our observation period. About 30% of control group
      members obtained health insurance coverage within one year following enrollment.
      We use two-stage least square models to estimate the impact on those who would
      not have obtained health insurance coverage without the demonstration project and
      find larger effects on self-reported health and mental health among these SSDI
      beneficiaries. Finally, we examine distributional impacts to show that mean
      impacts miss meaningful effects.

PMID- 23000874
TI  - Cordycepin (3'-deoxyadenosine) attenuates age-related oxidative stress and
      ameliorates antioxidant capacity in rats.
AB  - Free radical-induced oxidative damage is considered to be the most important
      consequence of the aging process. The activities and capacities of antioxidant
      systems of cells decline with increased age, leading to the gradual loss of pro
      oxidant/antioxidant balance and resulting in increased oxidative stress. Our
      investigation was focused on the effects of cordycepin (3'-deoxyadenosine) on
      lipid peroxidation and antioxidation in aged rats. Age-associated decline in the
      activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced
      glutathione (GSH), vitamin C and vitamin E, and elevated levels of
      malondialdehyde (MDA) were observed in the liver, kidneys, heart and lungs of
      aged rats, when compared to young rats. Furthermore, serum aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine were
      found to be significantly elevated in aged rats compared to young rats. Aged rats
      receiving cordycepin treatment show increased activity of SOD, CAT, GPx, GR and
      GST, and elevated levels of GSH, and vitamins C and E such that the values of
      most of these parameters did not differ significantly from those found in young
      rats. In addition, the levels of MDA, AST, ALT, urea and creatinine became
      reduced upon administration of cordycepin to aged rats. These results suggest
      that cordycepin is effective for restoring antioxidant status and decreasing
      lipid peroxidation in aged rats.

PMID- 23000876
TI  - Cutaneous reactions to novel therapeutics.
AB  - In the last 2 decades the introduction new biologic agents such as tumor necrosis
      factor alpha inhibitors has resulted in potent disease modifying effects in a
      variety of immune-mediated diseases. In addition, there were major advancements
      in cancer treatment due to chemotherapeutic agents including granulocyte
      macrophage-colony-stimulating factor, interferon, epidermal growth factor
      receptor inhibitors, and kinase inhibitors for the treatment of hematologic
      malignancies as well as solid tumors. However, a variety of toxicities including
      cutaneous reactions is seen in association with these agents. Awareness of
      commonly associated skin toxicities and recognition of corresponding histologic
      features is of importance.

PMID- 23000875
TI  - Effects of DHA-phospholipids, melatonin and tryptophan supplementation on
      erythrocyte membrane physico-chemical properties in elderly patients suffering
      from mild cognitive impairment.
AB  - A randomized, double-blind placebo-controlled clinical trial was carried out to
      assess the efficacy of a docosahexenoic acid (DHA)-phospholipids, melatonin and
      tryptophan supplemented diet in improving the erythrocyte oxidative stress,
      membrane fluidity and membrane-bound enzyme activities of elderly subjects
      suffering from mild cognitive impairment (MCI). These subjects were randomly
      assigned to the supplement group (11 subjects, 9F and 2M; age 85.3+/-5.3y) or
      placebo group (14-matched subjects, 11F and 3M; 86.1+/-6.5). The duration of the
      treatment was 12weeks. The placebo group showed no significant changes in
      erythrocyte membrane composition and function. The erythrocyte membranes of the
      supplement group showed a significant increase in eicosapentenoic acid,
      docosapentenoic acid and DHA concentrations and a significant decrease in
      arachidonic acid, malondialdehyde and lipofuscin levels. These changes in
      membrane composition resulted in an increase in the unsaturation index, membrane
      fluidity and acetylcholine esterase activity. Moreover, a significant increase in
      the ratio between reduced and oxidized glutathione was observed in the
      erythrocyte of the supplement group. Although this study is a preliminary
      investigation, we believe these findings to be of great speculative and
      interpretative interest to better understand the complex and multi-factorial
      mechanisms behind the possible links between diets, their functional components
      and possible molecular processes that contribute to increasing the risk of
      developing MCI and Alzheimer's.

PMID- 23000877
TI  - An experimental study of tissue reaction to hyaluronic acid (Restylane) and
      polymethylmethacrylate (Metacrill) in the mouse.
AB  - The aging skin is a challenge for medical science. Plastic surgeons and
      dermatologists are called every day to solve problems like filling wrinkles or
      folds. The material used must be biocompatible because abnormal reactions may
      cause catastrophic results. This study analyzes the biological behavior of
      polymethylmethacrylate (Metacrill) and hyaluronic acid (Restylane), using a
      histopathologic study in mice. A prospective study was performed using 40 mice
      for each substance: polymethylmethacrylate or hyaluronic acid was injected into
      the right ear, the left ear been used as a control. Histopathologic analyses of
      the right ear, liver, and kidney were performed at intervals during the study and
      revealed the development of a granulomatous reaction with fibrosis and absorption
      of spheres and signs of liver and kidney sistematization for
      polymethylmethacrylate. A discrete cellular reaction, with less formation of
      fibrosis, and no giant cells were seen in the mice injected with hyaluronic acid.

PMID- 23000878
TI  - The art and science of surgical margins for the dermatopathologist.
AB  - Basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and primary cutaneous
      melanoma (PCM) are the major forms of skin cancer. Surgical excision is one of
      the most frequently utilized treatment modalities for these tumors. METHODS:
      literature review. RESULTS: recommendations for lateral surgical excision margin
      (LEM) for BCCs is 4 mm for low-risk BCCs and Mohs surgery or resection with
      complete circumferential peripheral and deep margin assessment for high risk.
      Recommended LEM is 4-6 mm for low-risk SCCs and Mohs surgery or resection with
      complete circumferential peripheral and deep margin assessment for high risk
      BCCs. If SCC or BCC is >20 mm in area L with no other high-risk factors and can
      be repaired primarily, 10-mm clinical margins may be used. Recommended LEM is 5
      mm for melanoma-in-situ; 1 cm for PCM <1 mm (Breslow); 1-2 cm for PCM 1.01-2 mm
      (Breslow); and, 2-3 cm for high-risk PCM >2.01 mm (Breslow). Tumor subtype
      specific recommendations for histologic margins are offered which provide the
      greatest degree of certainty regarding the completeness of excision. CONCLUSION:
      Recommendations can be made regarding appropriate surgical excision margins by
      classifying skin cancers as low-risk or high-risk based on histopathological and
      clinical factors. Ascertaining that histopathologic margins are free of tumor is
      not a perfect science and requires thoughtful sampling, grossing, and staining
      procedures.

PMID- 23000879
TI  - Significantly decreased methylthioadenosine phosphorylase expression in malignant
      melanoma.

PMID- 23000880
TI  - Endoglin (CD105) and claudin-5 expression in cutaneous angiosarcoma.

PMID- 23000881
TI  - The specific expression pattern of globin mRNAs in Tibetan chicken during late
      embryonic stage under hypoxia.
AB  - Tibetan chicken (Gallus gallus) is a specific chicken breed with strong ability
      to resist hypoxia, especially during embryonic stage. Though this breed has lived
      in Tibet plateau for thousands of years, the adaptive mechanism in response to
      hypoxia is still unknown. In order to obtain a better understanding of the
      mechanism of hypoxic adaptability in high altitude, we analyzed the mRNA
      expression pattern of globins in the present study. The fertilized eggs from
      Tibetan chicken and dwarf recessive white chicken breeds were incubated under
      normoxic (21% O2) and hypoxic (13% O2) conditions, equivalent to the altitude of
      3600m. We observed that Tibetan chicken embryos had higher hatchability (48%) in
      hypoxia than their lowland controls (7.8%). Northern blot showed that globin mRNA
      expression in Tibetan chicken embryos differed greatly from lowland controls
      under hypoxia. The expressions of four dominant globin mRNAs, named alpha(A),
      alpha(D), beta(A) and beta(H), were significantly induced under hypoxia. Tibetan
      chicken embryos had lower globin mRNA level in red cells than that of lowland
      controls at day 19 (P<0.05). Based on real-time PCR the same result was
      confirmed. Furthermore, we observed accumulation of globins induced by hypoxia in
      red cells by performing the separation of globin analysis, showing higher level
      of globins in red cells of Tibetan chicken embryos than that of lowland chicken
      embryos. Overall, our results provide new evidence that flexible regulation of
      globins at the level of transcription and translation may play a role in allowing
      the Tibetan chicken embryo to resist hypoxia.

PMID- 23000882
TI  - Effects of quercetin and menadione on intestinal calcium absorption and the
      underlying mechanisms.
AB  - Quercetin (QT) could be considered as a potential therapeutic agent for different
      diseases due to its antioxidant, anti-inflammatory, antiviral and anticancer
      properties. This study was designed to investigate the ability of QT to protect
      the chick intestine against menadione (MEN) induced injury in vivo and in vitro.
      Four-week old chicks (Gallus gallus) were treated i.p. with 2.5MUmol of MEN/kg
      b.w. or with i.l. 50MUM QT or both. QT protected the intestinal Ca(2+) absorption
      against the inhibition caused by MEN, but QT alone did not modify. Glutathione
      (GSH) depletion provoked by MEN in chick enterocytes was abolished by QT
      treatment, whereas QT alone did not modify the intestinal GSH content. The
      enhancement of GSH peroxidase activity produced by MEN was blocked by QT
      treatment. In contrast, superoxide dismutase activity remained high after
      simultaneous treatment of enterocytes with MEN and QT. The flavonol also avoided
      changes in the mitochondrial membrane permeability (swelling) produced by MEN.
      The FasL/Fas/caspase-3 pathway was activated by MEN, effect that was abrogated by
      QT. In conclusion, QT may be useful in preventing inhibition of chick intestinal
      Ca(2+) absorption caused by MEN or other substances that deplete GSH, by blocking
      the oxidative stress and the FasL/Fas/caspase-3 pathway activation.

PMID- 23000883
TI  - Paracellular absorption in laboratory mice: Molecule size-dependent but low
      capacity.
AB  - Water-soluble nutrients are absorbed by the small intestine via transcellular and
      paracellular processes. The capacity for paracellular absorption seems lower in
      nonfliers than in fliers, although that conclusion rests largely on a comparison
      of relatively larger nonflying mammals (>155g) and relatively smaller flying
      birds (<155g). We report on paracellular absorption in laboratory mice, the
      smallest nonflying mammal species studied to date. Using a standard
      pharmacokinetic technique, we measured the extent of absorption (fractional
      absorption=f) of inert carbohydrate probes: L-arabinose (M(r)=150.13Da) and
      cellobiose (342.3) that are absorbed exclusively by the paracellular route, and 3
      O-methyl D-glucose (3OMD-glucose) (M(r)=194) absorbed both paracellularly and
      transcellularly. f was measured accurately in urine collection trials of 5-10h
      duration. Absorption of 3OMD-glucose by mice was essentially complete (f=0.95+/
      0.07) and much higher than that for L-arabinose (f=0.21+/-0.02), indicating that
      in mice, like other nonflying mammals, >80% of glucose is absorbed by mediated
      process(es) rather than the passive, paracellular route. As in all other
      vertebrates, absorption of cellobiose (f=0.13+/-0.02) was even lower than that
      for L-arabinose, suggesting an equivalent molecular size cut-off for flying and
      nonflying animals and thus a comparable effective TJ aperture. An important
      ecological implication is that smaller water-soluble plant secondary metabolites
      that have been shown to be absorbed by the paracellular path in cell culture,
      such as phenolics and alkaloids, might be absorbed in substantial amounts by bats
      and small birds relative to nonflying mammals such as mice.

PMID- 23000884
TI  - Directed patterning of the self-assembled silk-elastin-like nanofibers using a
      nanomechanical stimulus.
AB  - We investigate the effects of the frequency and density of a nanomechanical
      stimulus on nucleation and growth of silk-elastin-like protein polymer (SELP)
      nanofibers. Repetitive tappings are crucial to create nucleation areas and a
      potential molecular level mechanism was proposed. Using this technique
      mechanically guided nanofiber patterns were successfully created.

PMID- 23000885
TI  - The performance of density functional based methods in the description of
      selected biological systems and processes.
AB  - The catalytic mechanism of the purple acid phosphatase enzyme, electronic and
      structural properties of AT(GC)Zn(2)(OH)(2)(H(2)O)(2), a metal mediated DNA
      dimer, and UV-vis spectroscopic features of the chlorophyll-a (Chl-a) system, a
      potential photosensitizer, are the three different and interesting topics chosen
      to verify how the oldest and the most recent density functional methods work in
      the description of biological systems. Reported data indicate that good results
      can be obtained provided that computational strategies, exchange-correlation
      functionals and basis sets are carefully selected and applied.

PMID- 23000886
TI  - S100B: role in cardiac remodeling and function following myocardial infarction in
      diabetes.
AB  - AIM: S100B plays a role in cardiac remodeling following myocardial infarction
      (MI) and in diabetic vascular complications but not examined in diabetic
      myocardium. We thus examined the effects of targeted deletion of S100B gene on
      post-MI hearts. MAIN METHODS: Coronary artery ligation or sham was performed 15
      weeks after streptozotocin (STZ) or vehicle injection in wild-type (WT) and S100B
      knock-out (BKO) mice. Left ventricular (LV) structural and functional remodeling
      was studied 35 days after induction of MI. KEY FINDINGS: In diabetes, post-MI
      remodeling exhibited an attenuated increase in LV mass, dilation, and myocyte
      hypertrophy in association with increased apoptosis and fibrosis and reduced
      matrix metalloproteinase-2 (MMP-2) activity. Despite reduced LV dilation,
      impairment of cardiac function was similar to non-diabetic controls. Both
      diabetes and MI alone induced myocardial S100B and its canonical receptor for
      advanced glycation end product (RAGE) expression. By contrast, in post-MI
      diabetic myocardium, S100B expression was attenuated. Diabetic BKO, following MI
      demonstrated increased ventricular dilation compared to WT, in association with
      greater impairment of cardiac function, GLUT4 expression and systemic AGE levels.
      SIGNIFICANCE: These data suggest that S100B expression may serve to modulate
      cardiac metabolism and adverse consequences of AGE in diabetic post-MI remodeling
      and function.

PMID- 23000887
TI  - Hair growth-promoting effect of Aconiti Ciliare Tuber extract mediated by the
      activation of Wnt/beta-catenin signaling.
AB  - AIMS: The activation of Wnt/beta-catenin signaling pathway plays an important
      role in hair follicle morphogenesis by stimulating bulge stem cells. This study
      was to obtain the activator of Wnt/beta-catenin signaling pathway from natural
      products and to determine whether this activator can induce anagen hair growth in
      mice. MAIN METHODS: To identify materials that activate Wnt/beta-catenin
      signaling pathway, 800 natural product extracts were screened using pTOPFlash
      assay and neural progenitor cell (NPC) differentiation assay. A selected extract
      was further tested for its effects on alkaline phosphatase (ALP) activity in
      human immortalized dermal papilla cell (iDPC) and the proliferation in iDPC and
      immortalized rat vibrissa DPC (RvDP). Finally, hair growth-promoting effects were
      evaluated in the dorsal skin of C57BL/6 mice. KEY FINDINGS: Aconiti Ciliare Tuber
      (ACT) extract was one of the most active materials in both pTOPFlash and NPC
      differentiation assays. It promoted the differentiation of NPC cells even under
      proliferation-stimulating conditions (basic fibroblast growth factor: bFGF). It
      also increased ALP activity and proliferation of iDPC in dose-dependent manners,
      and it stimulated the induction of the anagen hair growth in C57BL/6 mice. These
      results suggest that ACT extract activates the Wnt/beta-catenin signaling pathway
      by enhancing beta-catenin transcription and has the potential to promote the
      induction of hair growth via activation of the stem cell activity of the dermal
      papilla cells. SIGNIFICANCE: This is the first report indicating benefits of ACT
      extract in hair loss prevention by triggering the activation of Wnt/beta-catenin
      signaling pathway and induction of the anagen hair growth in mice.

PMID- 23000888
TI  - Signal enhancement of protein binding by electrodeposited gold nanostructures for
      applications in Kretschmann-type SPR sensors.
AB  - We propose a novel Kretschmann-type surface plasmon resonance (SPR) sensor chip
      having a surface covered with electrodeposited gold nanostructures to enhance the
      sensitivity of SPR biosensing. The nanostructure is three-dimensional and has a
      larger surface area than a conventional flat surface chip, which increases the
      amount of protein binding and also induces a large change in the effective
      dielectric constant of the sensing area. The gold nanostructures were formed by
      electrodeposition under galvanostatic conditions, so their size could be
      controlled by manipulating the deposition time and current. The sensing
      characteristics, including the concentration dependence and noise level,
      indicated that the performance of the resulting chip (called a Au-black chip) was
      equivalent to that of a conventional sensor chip. We also determined the optimal
      electrodeposition conditions to obtain a sharp SPR curve for protein detection
      assay; the optimal thickness of the gold layer was 50-60 nm. Enhanced protein
      sensing was demonstrated by using a binding assay of anti-BSA antibody and BSA
      molecules. The protein binding signal was several times higher than that of the
      conventional assay. The insights into electrodeposition for SPR sensing presented
      here will enable improved sensitivity for detecting low-concentration and small
      proteins.

PMID- 23000889
TI  - Clinical outcomes of chemotherapy for diabetic and nondiabetic patients with
      pancreatic cancer: better prognosis with statin use in diabetic patients.
AB  - OBJECTIVES: The aim of this study was to clarify the impact of diabetes mellitus
      (DM) as well as antidiabetic, antihypertensive, and antihyperlipidemic
      medications such as metformin and statins on survival in patients with advanced
      pancreatic cancer receiving chemotherapy. METHODS: We retrospectively reviewed
      the medical records of 250 patients with advanced pancreatic cancer receiving
      chemotherapy. Multivariate analyses of prognostic factors for survival were
      performed both in overall population and in subgroups with and without DM.
      RESULTS: Diabetes mellitus was diagnosed in 124 patients (50%) who had less
      distant metastasis and more hypertension. Thirty patients received statin for
      hyperlipidemia. Overall survival was 13.3 versus 10.0 months with and without DM
      (P = 0.084), but hazard ratio of DM was 1.05 (P = 0.758) in the multivariate
      analysis. Subgroup analysis of diabetic patients, but not in non-diabetic
      patients, demonstrated use of statins (hazard ratio, 0.40; P = 0.010) as a
      prognostic factor, as well as distant metastasis, performance status, combination
      therapy with gemcitabine and S-1, and use of angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers. No antidiabetic medications were
      prognostic factors. CONCLUSIONS: Neither DM nor antidiabetic treatment had
      prognostic impact on advanced pancreatic cancer. Statin use was associated with
      better survival in the diabetic patients.

PMID- 23000890
TI  - Effect and cost of treatment for acute pancreatitis with or without gabexate
      mesylate: a propensity score analysis using a nationwide administrative database.
AB  - OBJECTIVES: Despite a lack of evidence, gabexate mesylate (GM) is routinely used
      for the treatment of acute pancreatitis (AP) in some countries. The present study
      examined the effect and cost of GM for AP treatment using the Japanese Diagnosis
      Procedure Combination database. METHODS: We performed a propensity score analysis
      to compare inhospital mortality, length of stay (LOS), and total costs between
      patients with AP treated with GM and those without GM in 2010. RESULTS: We
      identified 2483 patients treated with GM and 890 patients without GM. Overall,
      77% of the patients treated with GM were nonsevere AP cases. The propensity
      matched 707 pairs showed no significant difference between GM users and nonusers
      in inhospital mortality or median length of stay in nonsevere AP (1.0% vs 1.2%, P
      = 0.789; 10 vs 10 days, P = 0.160) and severe AP (8.4% vs 5.0%, P = 0.438; 12 vs
      14 days, P = 0.487) cases. Total costs were significantly different between the
      GM users and the nonusers in nonsevere AP cases (US$4982 vs US$4373, P < 0.001),
      but not in severe AP cases ($6605 vs $6490, P = 0.764). CONCLUSIONS: Using GM for
      nonsevere AP cannot be justified because of higher costs without significant
      effects. Gabexate mesylate use is also not justifiable for severe AP because it
      does not reduce mortality or length of stay.

PMID- 23000891
TI  - Heme oxygenase 1-generated carbon monoxide and biliverdin attenuate the course of
      experimental necrotizing pancreatitis.
AB  - OBJECTIVE: The cytoprotective enzyme heme oxygenase 1 (HO-1) is highly up
      regulated in acute pancreatitis (AP). In this study, we tested its metabolites as
      potential therapeutic agents for AP in rats. METHODS: Acute necrotizing
      pancreatitis was induced by retrograde intraductal injection of sodium
      taurocholate in rats. Biliverdin hydrochloride (BV HCl) (50 MUmol/kg
      subcutaneously), the carbon monoxide, donor methylene chloride (MC) (500 mg/kg
      orally), or iron-chelating desferrioxamine (DFO) (125 mg/kg subcutaneously) were
      administered in a therapeutic manner starting with the first dose 4 hours after
      taurocholate injection to mimic the effects of HO-1 metabolites. RESULTS:
      Administration of BV HCl, MC, or DFO showed significant reduction of inflammatory
      activity in comparison to controls leading to lower myeloperoxidase activity in
      the pancreas, less edema, lower ascites volumes, and preservation of tissue
      integrity (P < 0.05). Administration of either BV HCl or MC markedly increased 5
      day survival rate (70% and 75% vs 40%; P < 0.05), whereas DFO had no significant
      effect on survival (60%). When given in therapeutic manner, all 3 substances led
      to diminished nuclear factor kappaB activity in the pancreas (P < 0.05).
      CONCLUSIONS: Therapeutic use of BV HCl and MC led to marked reduction of
      mortality in experimental pancreatitis. Thus, HO-1 metabolites may present a
      novel therapeutic approach in AP treatment.

PMID- 23000892
TI  - The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo.
AB  - OBJECTIVES: The flavonoid quercetin holds promise as an antitumor agent in
      several preclinical animal models. However, the efficacy of oral administration
      of quercetin in a pancreatic cancer mouse model is unknown. METHODS: The
      antiproliferative effects of quercetin alone or in combination with gemcitabine
      were tested in 2 human pancreatic cancer cell lines using cell count and MTT
      assays. Apoptosis was evaluated by flow cytometry. Tumor growth in vivo was
      investigated in an orthotopic pancreatic cancer animal model using
      bioluminescence. Quercetin was administered orally in the diet. RESULTS:
      Quercetin inhibited the growth of pancreatic cancer cell lines, which was caused
      by an induction of apoptosis. In addition, dietary supplementation of quercetin
      attenuated the growth of orthotopically transplanted pancreatic xenografts. The
      combination of gemcitabine and quercetin had no additional effect compared with
      quercetin alone. In vivo quercetin caused significant apoptosis and reduced tumor
      cell proliferation. CONCLUSIONS: Our data provide evidence that oral
      administration of quercetin was capable of inhibiting growth of orthotopic
      pancreatic tumors in a nude mouse model. These data suggest a possible benefit of
      quercetin in patients with pancreatic cancer.

PMID- 23000893
TI  - Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers.
AB  - OBJECTIVES: In pancreatic cancer (PaC), the prevalence of diabetes mellitus (DM),
      especially new-onset DM (<=36 months of PaC diagnosis), is high. To determine if
      this observation is unique to PaC, we compared the prevalence and characteristics
      of DM in lung, breast, prostate, and colorectal cancers with PaC and noncancer
      controls. METHODS: We retrospectively reviewed the medical records of 500
      consecutive patients with cancer (100 each with lung, breast, prostate, and
      colorectal cancers and PaC) and 100 noncancer controls. RESULTS: Patients with
      PaC (mean age +/- SD, 71.6 +/- 9.4 years; 53% men) had a significantly (P <
      0.0001) higher prevalence of DM (68%) compared to age-matched patients with lung
      (mean age +/- SD, 71.6 +/- 9.4 years; 59% men; and 19.6% DM), breast (mean age +/
      SD, 71.6 +/- 9.6 years; 100% women; and 19.4% DM), prostate (mean age +/- SD,
      71.3 +/- 9.4 years; 100% men; and 14.8% DM), and colorectal cancer (mean age +/-
      SD, 71.6 +/- 9.5 years; 56% men; and 20.7% DM), and noncancer controls (mean age
      +/- SD, 70.7 +/- 9.2 years; 57% men; and 23.5% DM). Among the patients with PaC,
      40% developed DM in the 36 months preceding the diagnosis of PaC compared with
      3.3% to 5.7% in the other groups (P < 0.0001). CONCLUSIONS: Whereas the
      prevalence of DM in PaC is very high, DM prevalence in other common cancers is no
      different from that in noncancer controls. In particular, new-onset DM is a
      phenomenon that is unique to PaC.

PMID- 23000894
TI  - Measuring disparities in immunisation coverage among children in New Zealand.
AB  - For the past 20 years, New Zealand has experienced low immunisation coverage
      levels. Following the introduction of the National Immunisation Register (NIR) in
      2005 many practitioners envisaged improved overall immunisation uptake through
      enhanced surveillance and monitoring capacities. This study aimed to investigate
      the geographical distribution and variables associated with disparities in
      immunisation uptake in New Zealand using a large NIR data set of children aged 12
      months old in 2007-2009. DHB immunisation uptake was adjusted for individual
      ethnicity and deprivation status, year of birth and geographic location.
      Substantial variations in uptake by ethnicity and District Health Board (DHB)
      level were evident. Maori (NZ indigenous) and 'Other' ethnicity remain a
      substantial risk factor for low immunisation uptake after controlling for socio
      economic deprivation. In addition, a general north-south gradient was confirmed
      across New Zealand. Current immunisation programme strategies for planners and
      providers in New Zealand need to recognise varying DHB compositions in order to
      provide efficient service provision and to focus on those groups at higher risk
      of not being immunised.

PMID- 23000895
TI  - Amount and environmental predictors of outdoor playtime at home and school: a
      cross-sectional analysis of a national sample of preschool-aged children
      attending Head Start.
AB  - Outdoor play is an important contributor to children's physical activity and the
      prevalence, correlates, and environmental predictors of it among young children
      are not well characterized. This study aims to estimate the amount of time
      preschool-aged children attending Head Start spend playing outdoors at home and
      school, and whether aspects of the home and school environment are associated
      with greater outdoor play. We analyzed data (n=2529) collected in spring 2007 in
      the Head Start Family and Child Experiences Survey (FACES). Overall, 37.5% of
      children played outside at home >2h per weekday. Children who had a yard near
      home to play in or who had visited a park or playground or gone on a picnic with
      a family member in the last month were more likely to have >2h per weekday
      outdoor play at home, but having a playground within walking distance of the home
      was not related to home outdoor playtime. On average children played outdoors at
      Head Start for 36 min per day. The amount of time children played outdoors at
      home was not related to school outdoor time.

PMID- 23000896
TI  - Blood compatible microfluidic system for pharmacokinetic studies in small
      animals.
AB  - New radiotracer developments for nuclear medicine imaging require the analysis of
      blood as a function of time in small animal models. A microfluidic device was
      developed to monitor the radioactivity concentration in the blood of rats and
      mice in real time. The microfluidic technology enables a large capture solid
      angle and a reduction in the separation distance between the sample and detector,
      thus increasing the detection efficiency. This in turn allows a reduction of the
      required detection volume without compromising sensitivity, an important
      advantage with rodent models having a small total blood volume (a few ml). A
      robust fabrication process was developed to manufacture the microchannels on top
      of unpackaged p-i-n photodiodes without altering detector performance. The
      microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU
      8 but with improved resistance to stress-induced fissuring. Surface passivation
      of the KMPR enables non-diluted whole blood to flow through the channel for up to
      20 min at low speed without clotting. The microfluidic device was embedded in a
      portable blood counter with dedicated electronics, pumping unit and computer
      control software for utilisation next to a small animal nuclear imaging scanner.
      Experimental measurements confirmed model predictions and showed a 4- to 19-fold
      improvement in detection efficiency over existing catheter-based devices,
      enabling a commensurate reduction in sampled blood volume. A linear dose-response
      relationship was demonstrated for radioactivity concentrations typical of
      experiments with rodents. The system was successfully used to measure the blood
      input function of rats in real time after radiotracer injection.

PMID- 23000898
TI  - Controlling interneuron activity in Caenorhabditis elegans to evoke chemotactic
      behaviour.
AB  - Animals locate and track chemoattractive gradients in the environment to find
      food. With its small nervous system, Caenorhabditis elegans is a good model
      system in which to understand how the dynamics of neural activity control this
      search behaviour. Extensive work on the nematode has identified the neurons that
      are necessary for the different locomotory behaviours underlying chemotaxis
      through the use of laser ablation, activity recording in immobilized animals and
      the study of mutants. However, we do not know the neural activity patterns in C.
      elegans that are sufficient to control its complex chemotactic behaviour. To
      understand how the activity in its interneurons coordinate different motor
      programs to lead the animal to food, here we used optogenetics and new optical
      tools to manipulate neural activity directly in freely moving animals to evoke
      chemotactic behaviour. By deducing the classes of activity patterns triggered
      during chemotaxis and exciting individual neurons with these patterns, we
      identified interneurons that control the essential locomotory programs for this
      behaviour. Notably, we discovered that controlling the dynamics of activity in
      just one interneuron pair (AIY) was sufficient to force the animal to locate,
      turn towards and track virtual light gradients. Two distinct activity patterns
      triggered in AIY as the animal moved through the gradient controlled reversals
      and gradual turns to drive chemotactic behaviour. Because AIY neurons are post
      synaptic to most chemosensory and thermosensory neurons, it is probable that
      these activity patterns in AIY have an important role in controlling and
      coordinating different taxis behaviours of the animal.

PMID- 23000899
TI  - In vivo genome editing using a high-efficiency TALEN system.
AB  - The zebrafish (Danio rerio) is increasingly being used to study basic vertebrate
      biology and human disease with a rich array of in vivo genetic and molecular
      tools. However, the inability to readily modify the genome in a targeted fashion
      has been a bottleneck in the field. Here we show that improvements in artificial
      transcription activator-like effector nucleases (TALENs) provide a powerful new
      approach for targeted zebrafish genome editing and functional genomic
      applications. Using the GoldyTALEN modified scaffold and zebrafish delivery
      system, we show that this enhanced TALEN toolkit has a high efficiency in
      inducing locus-specific DNA breaks in somatic and germline tissues. At some loci,
      this efficacy approaches 100%, including biallelic conversion in somatic tissues
      that mimics phenotypes seen using morpholino-based targeted gene knockdowns. With
      this updated TALEN system, we successfully used single-stranded DNA
      oligonucleotides to precisely modify sequences at predefined locations in the
      zebrafish genome through homology-directed repair, including the introduction of
      a custom-designed EcoRV site and a modified loxP (mloxP) sequence into somatic
      tissue in vivo. We further show successful germline transmission of both EcoRV
      and mloxP engineered chromosomes. This combined approach offers the potential to
      model genetic variation as well as to generate targeted conditional alleles.

PMID- 23000900
TI  - Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11.
AB  - In mammals, one of the most pronounced consequences of viral infection is the
      induction of type I interferons, cytokines with potent antiviral activity.
      Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes
      (ISGs) that are also induced directly by pathogens via the interferon regulatory
      factor 3 (IRF3) pathway. However, many ISGs are of unknown or incompletely
      understood function. Here we show that human SLFN11 potently and specifically
      abrogates the production of retroviruses such as human immunodeficiency virus 1
      (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the
      retroviral infection cycle, including reverse transcription, integration and
      transcription. Rather, SLFN11 acts at the late stage of virus production by
      selectively inhibiting the expression of viral proteins in a codon-usage
      dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts
      changes in the tRNA pool elicited by the presence of HIV. Our studies identified
      a novel antiviral mechanism within the innate immune response, in which SLFN11
      selectively inhibits viral protein synthesis in HIV-infected cells by means of
      codon-bias discrimination.

PMID- 23000901
TI  - Structure of AMP-PNP-bound vitamin B12 transporter BtuCD-F.
AB  - The ATP-binding cassette (ABC) transporter BtuCD mediates the uptake of vitamin
      B(12) across the inner membrane of Escherichia coli. Previous structures have
      shown the conformations of apo states, but the transport mechanism has remained
      unclear. Here we report the 3.5 A crystal structure of the transporter-binding
      protein complex BtuCD-BtuF (BtuCD-F) trapped in an beta-gamma-imidoadenosine 5'
      phosphate (AMP-PNP)-bound intermediate state. Although the ABC domains (BtuD
      subunits) form the expected closed sandwich dimer, the membrane-spanning BtuC
      subunits adopt a new conformation, with the central translocation pathway sealed
      by a previously unrecognized cytoplasmic gate. A fully enclosed cavity is thus
      formed approximately halfway across the membrane. It is large enough to
      accommodate a vitamin B(12) molecule, and radioligand trapping showed that
      liposome-reconstituted BtuCD-F indeed contains bound B(12) in the presence of AMP
      PNP. In combination with engineered disulphide crosslinking and functional
      assays, our data suggest an unexpected peristaltic transport mechanism that is
      distinct from those observed in other ABC transporters.

PMID- 23000897
TI  - Comprehensive molecular portraits of human breast tumours.
AB  - We analysed primary breast cancers by genomic DNA copy number arrays, DNA
      methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and
      reverse-phase protein arrays. Our ability to integrate information across
      platforms provided key insights into previously defined gene expression subtypes
      and demonstrated the existence of four main breast cancer classes when combining
      data from five platforms, each of which shows significant molecular
      heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3)
      occurred at >10% incidence across all breast cancers; however, there were
      numerous subtype-associated and novel gene mutations including the enrichment of
      specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We
      identified two novel protein-expression-defined subgroups, possibly produced by
      stromal/microenvironmental elements, and integrated analyses identified specific
      signalling pathways dominant in each molecular subtype including a
      HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2
      enriched expression subtype. Comparison of basal-like breast tumours with high
      grade serous ovarian tumours showed many molecular commonalities, indicating a
      related aetiology and similar therapeutic opportunities. The biological finding
      of the four main breast cancer subtypes caused by different subsets of genetic
      and epigenetic abnormalities raises the hypothesis that much of the clinically
      observable plasticity and heterogeneity occurs within, and not across, these
      major biological subtypes of breast cancer.

PMID- 23000903
TI  - Host cell Golgi anti-apoptotic protein (GAAP) and growth of Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae protein CPn0809 is a type three secretion system substrate,
      the exact function of which in infection pathogenesis has remained unknown. In
      this study, we identified by yeast two-hybrid screening a potential host cell
      interaction partner of CPn0809, Golgi anti-apoptotic protein (GAAP), a conserved
      protein found in eukaryotic cells. GAAP gene is expressed at relatively constant
      levels and its expression remained stable also after C. pneumoniae infection. The
      interaction between GAAP and C. pneumoniae was suggested by transfection studies.
      GAAP knock-down by siRNA in infected A549 cells resulted in an increased number
      of C. pneumoniae genomes and growth of the bacteria as judged by quantitative PCR
      and inclusion counts, respectively. Silencing of GAAP did not make the A549 cells
      more susceptible to apoptosis per se, and infection with C. pneumoniae prevented
      staurosporin-induced apoptosis also in transfected cultures. Taken together, the
      proposed interaction between C. pneumoniae and GAAP modulates bacterial growth in
      A549 cells.

PMID- 23000902
TI  - Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis
      elegans.
AB  - P-glycoprotein (P-gp) is an ATP-binding cassette transporter that confers
      multidrug resistance in cancer cells. It also affects the absorption,
      distribution and clearance of cancer-unrelated drugs and xenobiotics. For these
      reasons, the structure and function of P-gp have been studied extensively for
      decades. Here we present biochemical characterization of P-gp from Caenorhabditis
      elegans and its crystal structure at a resolution of 3.4 angstroms. We find that
      the apparent affinities of P-gp for anticancer drugs actinomycin D and paclitaxel
      are approximately 4,000 and 100 times higher, respectively, in the membrane
      bilayer than in detergent. This affinity enhancement highlights the importance of
      membrane partitioning when a drug accesses the transporter in the membrane.
      Furthermore, the transporter in the crystal structure opens its drug pathway at
      the level of the membrane's inner leaflet. In the helices flanking the opening to
      the membrane, we observe extended loops that may mediate drug binding, function
      as hinges to gate the pathway or both. We also find that the interface between
      the transmembrane and nucleotide-binding domains, which couples ATP hydrolysis to
      transport, contains a ball-and-socket joint and salt bridges similar to the ATP
      binding cassette importers, suggesting that ATP-binding cassette exporters and
      importers may use similar mechanisms to achieve alternating access for transport.
      Finally, a model of human P-gp derived from the structure of C. elegans P-gp not
      only is compatible with decades of biochemical analysis, but also helps to
      explain perplexing functional data regarding the Phe335Ala mutant. These results
      increase our understanding of the structure and function of this important
      molecule.

PMID- 23000904
TI  - The CDKN2A and MAP kinase pathways: molecular roads to primary oral mucosal
      melanoma.
AB  - The etiology and pathogenesis of oral mucosal melanomas are poorly understood,
      and no intraoral risk factors have been identified. Recent studies have
      postulated that DNA repair mechanisms and cell growth pathways are involved in
      the development of melanoma-particularly changes in the CDKN2A (p16-cyclinD-Cdk
      pRb) and MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2 proteins). We examined
      the central components of the CDKN2A and RAS-RAF-MEK-ERK cascades by
      immunohistochemistry in a series of 35 primary oral melanomas by tissue
      microarray (TMA). We noted altered expression of the CDKN2A cascade proteins,
      although these modulations did not correlate significantly with clinical and
      pathological parameters. The expression of MAP kinase cascade proteins changed in
      most cases. We observed that 28.57% of cases were RAS-positive and that 82.85%
      and 74.28% of cases were positive for BRAF and ERK2, respectively; MEK2 and ERK1
      were not expressed in 48.57% and 80% of cases, and all cases were negative for
      MEK1. The absence of RAS and ERK1 and positivity for BRAF and ERK2 were
      associated with higher histological grade, vascular invasion, and metastasis.
      Expression of MEK2 was significantly linked to vascular invasion (P = 0.043). The
      CDKN2A and MAPK pathways require further study in mucosal melanomas, but our
      results highlight the significance of important alterations, particularly with
      regard to histological indicators of poor prognosis in primary oral mucosal
      melanomas, independent of UV exposure.

PMID- 23000905
TI  - Reconsidering the diagnostic and prognostic utility of LN-2 for undifferentiated
      pleomorphic sarcoma and atypical fibroxanthoma.
AB  - The topic of distinguishing atypical fibroxanthoma (AFX) from undifferentiated
      pleomorphic sarcoma (UPS), formerly malignant fibrous histiocytoma, is highly
      controversial. Although their clinical behavior is disparate, AFX and UPS
      commonly appear nearly identical on routine histopathologic examination. Although
      conceptually useful, subcategorization of UPS into superficial (confined to the
      dermis and subcutaneous tissue) and deep (involvement of fascia and deeper
      structures) types has not improved our ability to differentiate UPS from AFX.
      Numerous authors have purported LN-2 (CD74) immunopositivity as able to
      distinguish UPS from AFX and to predict those rare AFX likely to behave
      aggressively, although only a single prior study has been dedicated to evaluating
      this marker. We performed LN-2 staining of 14 AFX, 8 superficial UPS, and 65 deep
      UPS specimens using an identical protocol as described by prior authors. Of the
      73 total UPS specimens, only 1 (1.4%) stained strongly with LN-2, as compared
      with 3 of 14 (21%) AFX (P = 0.012). One of 2 (50%) clinically aggressive AFX
      tumors that later exhibited both local recurrence and metastasis stained strongly
      for LN-2, whereas 2 of 12 (17%) of the more indolent tumors stained strongly with
      this marker (P = 0.40). Our data do not replicate prior reports of LN-2 as a
      sensitive and specific marker for UPS, or as indicative of prognosis for AFX, and
      therefore does not support the use of LN-2 as either a diagnostic or prognostic
      marker.

PMID- 23000906
TI  - Cutaneous extramedullary plasmacytoma: clinical, prognostic, and interphase
      cytogenetic analysis.
AB  - Extramedullary plasmacytoma (EMP) of the skin is a rare indolent neoplasm that
      shares morphological and immunophenotypic features with plasma cell myeloma
      (PCM), but the molecular features that distinguish these two entities have not
      been defined. We reviewed the clinical characteristics, course, and molecular
      abnormalities in 7 cases of cutaneous EMP (cEMP); 2 patients had primary cEMP and
      5 had secondary cEMP. Two patients died of progressive extramedullary
      plasmacytoma, 1 without PCM; 1 patient who had only a hyperdiploid clone, died
      within 17 months of the diagnosis of cEMP; and 3 died of PCM. One patient, who
      had cEMP with a hyperdiploid clone and a 13q deletion, was alive 28 months after
      diagnosis. Our findings raise questions about the relative prognostic value of
      molecular aberrations observed in cEMP and PCM. The role of fluorescence in situ
      hybridization testing in predicting disease progression of cEMP remains to be
      defined.

PMID- 23000907
TI  - Progressive petechial and pigmented macules and papules on the lower extremities.

PMID- 23000909
TI  - Polymorphism and tautomeric preference in fenobam and the utility of NLO response
      to detect polymorphic impurities.
AB  - Crystal structures of polymorphs and solvatomorphs of the potential anxiolytic
      drug fenobam exhibit an exclusive preference for one of the two possible
      tautomeric structures. A novel methodology based on nonlinear optical response
      has been successfully employed to detect the presence of a polymorphic impurity
      in a mixture of polymorphs.

PMID- 23000910
TI  - Systematic literature review and evaluation of patient  reported outcome measures
      (PROMs) for asthma and  related allergic diseases.

PMID- 23000911
TI  - Cost-effectiveness of mometasone furoate nasal spray in the  treatment of acute
      rhinosinusitis.
AB  - BACKGROUND: Acute rhinosinusitis is a common disease with an increasing incidence
      rate. It causes substantial costs to the individual and to society through
      healthcare consumption and absence from work. The use of antibiotics is
      widespread in the treatment of acute rhinosinusitis, but increasing bacterial
      resistance is an argument for restricting excessive use of antibiotics. AIMS: The
      aim of this study was to analyse the cost-effectiveness of mometasone furoate
      nasal spray (MFNS) compared with amoxicillin or non-active treatment of mild to
      moderate acute rhinosinusitis in a Swedish setting. METHODS: A cost-effectiveness
      model was developed to capture the costs and health-related quality of life
      (HRQoL) over a 15-day period. Acute rhinosinusitis was modelled as changes in the
      Major Symptom Score. The model takes on a societal perspective in a Swedish
      setting. Efficacy data were taken from a randomised clinical study. The model has
      three treatment arms: (A) MFNS 200 MUg twice daily, (B) amoxicillin 500 mg three
      times daily, and (C) placebo. Information about resource utilisation and HRQoL
      was taken from a recent observational study. RESULTS: Costs were reduced and
      quality-adjusted life years were increased with MFNS 200 MUg twice daily compared
      with amoxicillin 500 mg three times daily. MFNS was cost-saving or cost-effective
      compared with amoxicillin or non-active treatment in the sensitivity analyses
      regardless of the HRQoL measurement used. CONCLUSIONS: This study shows that
      treatment with MFNS 200 MUg twice daily results in lower costs and improved HRQoL
      in acute rhinosinusitis compared with amoxicillin or self-medication.

PMID- 23000912
TI  - Evaluation of chemical mediators and cellular response during acute and chronic
      gut inflammatory response induced by dextran sodium sulfate in mice.
AB  - Inflammatory bowel disease (IBD) affects millions of people worldwide but its
      pathophysiology remains unclear. Therefore, experimental models of colitis have
      contributed crucially for the understanding of IBD, and also in the
      investigations for effective therapies. Herein we investigated the kinetics of
      inflammatory mediator production and cell infiltration during acute and chronic
      dextran sodium sulfate (DSS)-induced colitis. The induction phases with DSS were
      characterized by severe disease activity with massive colonic polymorphonuclear
      infiltration and increased levels of tumor necrosis factor-alpha (TNF-alpha),
      keratinocyte-derived chemokine (CXCL1/KC), interleukin (IL)-17 and vascular
      adhesion molecule-1 (VCAM-1). Interestingly, in the recovery periods, we found
      marked increase of anti-inflammatory mediators IL-10, IL-4, transforming growth
      factor-beta (TGF-beta) and cyclooxygenase 2 (COX-2) that seems be essential for
      the resolution of intestinal inflammation. Furthermore, nuclear factor kappaB
      (NFkappaB) and regulatory T cell marker forkhead box P3 (FoxP3) were increased
      gradually during experimental colitis, demonstrating a discrepant profile
      response and evident immune disbalance in the chronic phase of intestinal mucosal
      inflammation. Taken together, these results provide valuable information for
      studies on DSS-induced colitis and especially for the identification of
      biomarkers that predict disease course and possible therapeutic interventions.

PMID- 23000913
TI  - N-Acetylcysteine ethyl ester (NACET): a novel lipophilic cell-permeable cysteine
      derivative with an unusual pharmacokinetic feature and remarkable antioxidant
      potential.
AB  - Recent large clinical trials failed to confirm the supposed beneficial effects of
      N-acetylcysteine (NAC) in preventing oxidative stress-related diseases. This may
      be due to its low bioavailability. We thought that esterification of the carboxyl
      group of NAC to produce N-acetylcysteine ethyl ester (NACET) would drastically
      increase the lipophilicity of NAC, thus greatly improving its pharmacokinetics.
      In the present work, we report on representative chemical, pharmacological and
      anti-oxidant properties of NACET, especially in direct comparison with its
      congener NAC. We found that NACET is rapidly absorbed in rats after oral
      administration but reaches very low concentrations in plasma. This is due to a
      unique feature of NACET: it rapidly enters the cells where it is trapped being
      transformed into NAC and cysteine. After oral treatment, NACET (but not NAC) was
      able to increase significantly the glutathione content of most tissues examined,
      brain included, and to protect from paracetamol intoxication in the rat. NACET
      has also the unique feature to accumulate in human erythrocytes where it behaves
      as a potent protector against hydroperoxide-induced oxidative damage. Our study
      shows that being able to enter cells and to produce NAC and cysteine, NACET
      increases circulating hydrogen sulfide (H(2)S), thus representing a good
      candidate for the oral use as an H(2)S producer, with clear advantages over NAC.
      NACET has the potential to substitute NAC as a mucolytic agent, as a paracetamol
      antidote and as a GSH-related antioxidant.

PMID- 23000914
TI  - The PPARdelta-mediated inhibition of angiotensin II-induced premature senescence
      in human endothelial cells is SIRT1-dependent.
AB  - Cellular senescence has been implicated in endothelial dysfunctions affecting
      vascular tone and regeneration. The molecular mechanisms of vascular senescence
      are poorly understood. The present study demonstrates that upregulation of SIRT1
      by peroxisome proliferator-activated receptor (PPAR) delta attenuates premature
      senescence in angiotensin (Ang) II-treated human coronary artery endothelial
      cells (HCAECs). Activation of PPARdelta by the specific ligand GW501516
      significantly inhibited Ang II-induced premature senescence and generation of
      reactive oxygen species (ROS) in HCAECs. A marked concentration- and time
      dependent increase in the mRNA levels of SIRT1 was observed in GW501516-treated
      HCAECs. The effects of GW501516 were almost completely abolished in the presence
      of small interfering (si) RNA against PPARdelta, indicating that PPARdelta
      mediates the effects of GW501516. In addition, activation of PPARdelta, but not
      PPARalpha or PPARgamma, significantly enhanced SIRT1 promoter activity and
      protein expression. Down-regulation or inhibition of SIRT1 by siRNA or sirtinol
      abrogated the effects of PPARdelta on Ang II-induced premature senescence and ROS
      generation, respectively. Furthermore, resveratrol, a well-known activator of
      SIRT1, mimicked the action of PPARdelta on Ang II-induced premature senescence
      and ROS generation. Taken together, these results indicate that the anti
      senescent activities of PPARdelta may be achieved at least in part by fine tuning
      the expression of SIRT1 in the vascular endothelium.

PMID- 23000915
TI  - Piperine, an LXRalpha antagonist, protects against hepatic steatosis and improves
      insulin signaling in mice fed a high-fat diet.
AB  - This study investigated the role of piperine in the transcriptional regulation of
      liver X receptor alpha (LXRalpha) and the effects of dietary piperine on high-fat
      diet (HFD)-induced hepatic steatosis and insulin resistance in mice. Furthermore,
      we explored the potential molecular mechanisms through which the protective
      effects of piperine may work. In the present study, piperine significantly
      reduced ligand-induced LXRalpha activity in a dose-dependent manner and gradually
      disrupted the interaction between ligand-bound LXRalpha and GST-CBP. In mice, an
      HFD supplemented with 0.05% piperine (PSD) significantly decreased body and liver
      weight as well as plasma and hepatic lipid levels. In agreement with our in vitro
      study, in mice fed an HFD, dietary piperine markedly decreased LXRalpha mRNA
      expression and its lipogenic target genes (i.e., SREBP1c, ChREBPalpha, FAS, and
      CD36). Piperine also significantly decreased plasma insulin and glucose
      concentrations, while increasing insulin sensitivity in mice fed an HFD. In
      addition, piperine downregulated the expression of genes involved in ER stress,
      including GRP78, activating transcription factor 6, and eukaryotic translation
      initiation factor 2alpha, and upregulated GLUT2 translocation from the cytosol to
      the plasma membrane in the livers of PSD mice. Piperine antagonized LXRalpha
      transcriptional activity by abolishing the interaction of ligand-bound LXRalpha
      with the co-activator CBP. The effects of piperine on hepatic lipid accumulation
      were likely regulated via alterations in LXRalpha-mediated lipogenesis in mice
      fed an HFD. Dietary piperine also led to reduced ER stress and increased insulin
      sensitivity and prevented hepatic insulin resistance in mice fed the HFD.

PMID- 23000916
TI  - Pharmacological targeting of endoplasmic reticulum stress signaling in cancer.
AB  - The endoplasmic reticulum (ER) stress response constitutes a cellular process
      that can be triggered by a great variety of conditions that cause imbalances in
      intracellular homeostasis and threaten proper cell functioning. In response, the
      ER stress response activates an adaptive effort aimed at neutralizing these
      threats and reestablishing homeostasis. However, if these countermeasures are
      unsuccessful and severe imbalances persist, the ER stress response may abandon
      its pro-survival efforts and instead may initiate a pro-apoptotic program to
      eliminate the faulty cell for the benefit of the organism as a whole. Because
      vigorous growth of malignant tumors may create stressful conditions, such as
      hypoglycemia, hypoxia, or accumulation of misfolded proteins during revved up
      protein synthesis, the adaptive, pro-survival components of the ER stress
      response system (e.g., GRP78/BiP) are frequently found chronically activated in
      tumor cells. This differential to non-stressed normal cells has been proposed to
      represent an Achilles' heel of tumor cells that may be exploitable by therapeutic
      intervention. In this model, the goal would be to further aggravate the pre
      existing stress conditions in tumor cells with appropriate pharmacological
      agents, so that the already engaged pro-survival mechanism would be overwhelmed
      and the ER stress response forced to switch to its pro-apoptotic mode (e.g.,
      CHOP/GADD153). This review will discuss the principle of pharmacological ER
      stress aggravation, and will present preclinical models with promise for cancer
      therapeutic applications.

PMID- 23000917
TI  - Field ion microscope evaluation of tungsten nanotip shape using He and Ne imaging
      gases.
AB  - Field ion microscopy (FIM) using neon imaging gas was used to evaluate a W(111)
      nanotip shape during a nitrogen assisted etching and evaporation process. Using
      appropriate etching parameters a narrow ring of atoms centered about the tip axis
      appears in a helium generated image. Etching of tungsten atoms continues
      exclusively on the outside of this well-defined ring. By replacing helium imaging
      gas with neon, normally inaccessible crystal structure of a tip apex is revealed.
      Comparison of the original W(111) tip (before etching) and partly etched tip
      shows no atomic changes at the tip apex revealing extraordinarily spatially
      selective etching properties of the etching process. This observation is an
      important step towards a detailed understanding of the nitrogen assisted etching
      and evaporation process and will lead to better control over atomically defined
      tip shapes.

PMID- 23000918
TI  - Sampling excited state dynamics: influence of HOOP mode excitations in a retinal
      model.
AB  - Zero point energy and classical thermal sampling techniques are compared in semi
      classical photodynamics of the pentadienyliminium cation, a minimal retinal
      model. Using both methods, the effects of vibrational hydrogen-out-of-plane
      (HOOP) excitations on the photo-reactivity are probed at the ab initio CASSCF
      level. With 2376 individual trajectories the calculations reveal a clear picture
      of the relation between the excited state reaction coordinate, surface crossing
      and product generation. The productivity is strongly coupled with hydrogen
      torsion and the number of hopping attempts before the molecule finally decays.

PMID- 23000919
TI  - Arthroscopic inside-out repair of complete radial tears of the meniscus with a
      fibrin clot.
AB  - PURPOSE: To report on the results of 12 complete radial tears of the meniscus
      treated using arthroscopic inside-out repair with fibrin clots, the results
      showed good meniscal healing and excellent clinical outcomes. METHODS: From 2007
      to 2009, 12 patients with complete radial tears of the meniscus were treated by
      arthroscopic inside-out repair with fibrin clots. In all patients, the
      International Knee Documentation Committee (IKDC) subjective knee form and
      Lysholm score were determined pre- and post-operatively. We performed magnetic
      resonance imaging (MRI) and if indicated, we performed a second-look arthroscopic
      examination. RESULTS: At a mean of 30 +/- 4 postoperative months, the Lysholm
      score and IKDC subjective knee score had improved from 65 +/- 6 and 57 +/- 7 to
      94 +/- 3 and 92 +/- 3, respectively. Eleven of 12 cases showed complete healing
      on follow-up MRI. Six of 7 patients undergoing a second-look arthroscopic
      examination had healed completely. CONCLUSION: This study shows successful
      meniscal repairs using fibrin clots in complete radial tears. This surgical
      procedure appears to be a good treatment method for complete radial tear of the
      meniscus. LEVEL OF EVIDENCE: Case series, level IV.

PMID- 23000920
TI  - How successful are we in shoulder stabilization?

PMID- 23000921
TI  - Increased matrix metalloprotease-3 gene expression in ruptured rotator cuff
      tendons is associated with postoperative tendon retear.
AB  - PURPOSE: The role of matrix metalloproteases (MMPs) in ruptured rotator cuff
      tendons remains unknown. This study aimed to investigate the gene expression of
      MMPs in ruptured rotator cuff tendons and to compare their expression levels
      between patients with and without postoperative tendon retear. METHODS: Twenty
      four patients (a median age of 61 years: interquartile range, 55-66 years) with
      full-thickness rotator cuff tears were examined in this study. The marginal site
      of the ruptured tendon was harvested during surgery. The mRNA expression levels
      of collagen types I and III, MMP-1, MMP-3, MMP-7, MMP-9, MMP-13, tissue inhibitor
      of MMP (TIMP)-1, and TIMP-2 were analysed by real-time reverse transcription
      polymerase chain reaction. Postoperative retear was evaluated by magnetic
      resonance imaging at a minimum of 1 year following surgery. RESULTS: The mRNA
      expression levels of MMP-3 and TIMP-1 in ruptured rotator cuff tendons were
      significantly increased in patients with postoperative retear (n = 6), compared
      with patients without retear (n = 18) (P = 0.04). For collagens, MMP-1, MMP-7,
      MMP-9, MMP-13, and TIMP-2, there were no significant differences in the mRNA
      expression levels in ruptured tendons between patients with and without retear.
      CONCLUSIONS: These results suggest that, in addition to up-regulation of TIMP-1
      gene expression, increased MMP-3 gene expression in ruptured rotator cuff tendons
      is associated with postoperative tendon retear. Thus, drug therapy specifically
      targeting MMP-3 after rotator cuff repair should be considered in the future.

PMID- 23000922
TI  - Preoperative pain location is a poor predictor of outcome after Oxford
      unicompartmental knee arthroplasty at 1 and 5 years.
AB  - PURPOSE: Indications for unicompartmental knee arthroplasty (UKA) vary between
      units. Some authors have suggested, and many surgeons believe, that medial UKA
      should only be performed in patients who localise their pain to the medial joint
      line. This is despite research showing a poor correlation between patient
      reported location of pain and radiological or operative findings in
      osteoarthritis. The aim of this study is to determine the effect of patient
      reported preoperative pain location and functional outcome of UKA at 1 and 5
      years. METHODS: Preoperative pain location data were collected for 406 knees (380
      patients) undergoing Oxford medial UKA. Oxford Knee Score, American Knee Society
      Scores and Tegner activity scale were recorded preoperatively and at follow-up;
      272/406 (67 %) had pure medial pain, 25/406 (6 %) had pure anterior knee pain,
      and 109/406 (27 %) had mixed or generalised pain. None had pure lateral pain. The
      primary outcome interval is 1 year; 132/406 patients had attained 5 years by the
      time of analysis, and their 5-year data are presented. RESULTS: At 1 and 5 years,
      each group had improved significantly by each measure [mean DeltaOKS 15.6 (SD
      8.9) at year 1, 16.3 (9.3) at year 5]. There was no difference between the
      groups, nor between patients with and without anterior knee pain or isolated
      medial pain. CONCLUSIONS: No correlation is demonstrated between preoperative
      pain location and outcome. We conclude that localised medial pain should not be a
      prerequisite to UKA and that it may be performed in patients with generalised or
      anterior knee pain.

PMID- 23000923
TI  - Gold on paper-paper platform for Au-nanoprobe TB detection.
AB  - Tuberculosis (TB) remains one of the most serious infectious diseases in the
      world and the rate of new cases continues to increase. The development of cheap
      and simple methodologies capable of identifying TB causing agents belonging to
      the Mycobacterium tuberculosis Complex (MTBC), at point-of-need, in particular in
      resource-poor countries where the main TB epidemics are observed, is of paramount
      relevance for the timely and effective diagnosis and management of patients. TB
      molecular diagnostics, aimed at reducing the time of laboratory diagnostics from
      weeks to days, still require specialised technical personnel and labour intensive
      methods. Recent nanotechnology-based systems have been proposed to circumvent
      these limitations. Here, we report on a paper-based platform capable of
      integrating a previously developed Au-nanoprobe based MTBC detection assay-we
      call it "Gold on Paper". The Au-nanoprobe assay is processed and developed on a
      wax-printed microplate paper platform, allowing unequivocal identification of
      MTBC members and can be performed without specialised laboratory equipment. Upon
      integration of this Au-nanoprobe colorimetric assay onto the 384-microplate,
      differential colour scrutiny may be captured and analysed with a generic
      "smartphone" device. This strategy uses the mobile device to digitalise the
      intensity of the colour associated with each colorimetric assay, perform a Red
      Green Blue (RGB) analysis and transfer relevant information to an off-site lab,
      thus allowing for efficient diagnostics. Integration of the GPS location metadata
      of every test image may add a new dimension of information, allowing for real
      time epidemiologic data on MTBC identification.

PMID- 23000924
TI  - Crotonaldehyde induces apoptosis and immunosuppression in alveolar macrophages.
AB  - Crotonaldehyde, a highly toxic alpha, beta-unsaturated aldehyde, is a major
      component of cigarette smoke (CS) and a ubiquitous environmental pollutant.
      Exposure to crotonaldehyde-rich pollutants such as CS is associated with
      suppression of respiratory host defense against infections. The aim of this study
      was to evaluate the apoptotic and immunological effects of crotonaldehyde
      exposure in a rat alveolar macrophage (AM) cell line, NR8383. Our studies showed
      that crotonaldehyde induced AM cell death mainly via the apoptotic process.
      Crotonaldehyde also decreased the phagocytic activity of AMs. Crotonaldehyde
      caused inhibition of NO, TNF-alpha, IL-1beta and IL-12 production in AMs treated
      with lipopolysaccharide (LPS), which is probably related to inhibition of NF
      kappaB activation. These results indicate that crotonaldehyde can cause adverse
      effects in AMs via multiple mechanisms, and may contribute to compromised lung
      immunological response in smokers.

PMID- 23000925
TI  - Renilla luciferase-labeled Annexin V: a new probe for detection of apoptotic
      cells.
AB  - The Ca(2+)-dependent binding of Annexin V to phosphatidylserine on cell surfaces
      is a reliable marker for apoptosis that is widely used in flow cytometry based
      apoptosis assays. In this paper, we report a new class of Annexin V-based probes
      for apoptosis. Luciferase from Renilla reniformis (RLuc) was linked to Annexin V
      and expressed successfully in a soluble form in Escherichia coli BL21 (DE3). The
      new probe, Rluc/Annexin V, was purified and functionally assayed for detection of
      apoptosis in actinomycin D-induced apoptotic Jurkat cells. Moreover, the
      spontaneous apoptosis in neutrophils was shown using the new probe. The results
      indicate that Rluc/Annexin V can bind to the apoptotic cells, and the signal of
      Renilla luciferase can be detected by luminometric measurements. The availability
      of Rluc/Annexin V may be of potential commercial interest for improving current
      apoptosis assays.

PMID- 23000926
TI  - Domestic violence in India: need for public health action.

PMID- 23000927
TI  - Electron Spin Resonance and optical absorption spectroscopic studies of manganese
      centers in aluminium lead borate glasses.
AB  - Electron Spin Resonance (ESR) and optical absorption studies of
      5Al(2)O(3)+75H(3)BO(3)+(20-x)PbO+xMnSO(4) (where x=0.5, 1,1.5 and 2 mol% of
      MnSO(4)) glasses at room temperature have been studied. The ESR spectrum of all
      the glasses exhibits resonance signals with effective isotropic g values at ~2.0,
      3.3 and 4.3. The ESR resonance signal at isotropic g~2.0 has been attributed to
      Mn(2+) centers in an octahedral symmetry. The ESR resonance signals at isotropic
      g~3.3 and 4.3 have been attributed to the rhombic symmetry of the Mn(2+) ions.
      The zero-field splitting parameter (zfs) has been calculated from the intensities
      of the allowed hyperfine lines. The optical absorption spectrum exhibits an
      intense band in the visible region and it has been attributed to (5)E(g)
      >(5)T(2g) transition of Mn(3+)centers in an octahedral environment. The optical
      band gap and the Urbach energies have been calculated from the ultraviolet
      absorption edges.

PMID- 23000928
TI  - Quantum chemical studies and vibrational analysis of 4-acetyl benzonitrile, 4
      formyl benzonitrile and 4-hydroxy benzonitrile--a comparative study.
AB  - The FTIR and FT-Raman vibrational spectra of 4-actetyl benzonitrile, 4-formyl
      benzonitrile and 4-hydroxy benzonitrile molecules have been recorded in the range
      4000-400 and 4000-100 cm(-1), respectively. The complete vibrational assignment
      and analysis of the fundamental modes of the most stable geometry of the
      compounds were carried out using the experimental FTIR and FT-Raman data on the
      basis of peak positions, relative intensities and quantum chemical studies. The
      observed vibrational frequencies were compared with the theoretical wavenumbers
      of the optimised geometry of the compounds obtained from the DFT-B3LYP gradient
      calculations employing the standard 6-31G**, high level 6-311++G** and cc-pVDZ
      basis sets. The structural parameters and vibrational wavenumbers obtained from
      the DFT methods are in good agreement with the experimental data. With hope of
      providing more and effective information on the fundamental vibrations, total
      energy distributions of the fundamental modes have been performed by assuming
      C(s) point group symmetry. The effect of substituents -COCH(3), -CHO and -OH in
      the benzonitrile moiety have been analysed and compared. The kinetic and
      thermodynamic stability and chemical hardness of the molecule have been
      determined.

PMID- 23000929
TI  - Synthesis, luminescence properties of Eu(III) and Tb(III) complexes with a novel
      aromatic carboxylic acid and their interactions with bovine serum albumin.
AB  - A novel aromatic carboxylic acid ligand (L) was synthesized and its corresponding
      Eu(III) and Tb(III) complexes, Na(3)EuLCl(3).2H(2)O (EuL) and
      Na(3)TbLCl(3).3H(2)O (TbL), were successfully prepared. L and its corresponding
      complexes were characterized by means of MS, elemental analysis, IR, (1)H NMR and
      TG. The luminescence spectra of Eu(III) and Tb(III) complexes were investigated
      and the results showed that L was an efficient sensitizer for Eu(III) and Tb(III)
      luminescence. The interactions of L, EuL and TbL with bovine serum albumin (BSA)
      have been investigated through fluorescence spectroscopy under physiological
      conditions. The Stern-Volmer analysis indicated that the fluorescence quenching
      of BSA by L, EuL and TbL was resulted from static mechanism, and the binding
      constants (K(a)) were 2.22*10(4), 1.33*10(5) and 4.27*10(5) at 300 K,
      respectively. The binding sites (n) and the corresponding thermodynamic
      parameters DeltaH, DeltaS, and DeltaG were calculated at different temperatures.
      According to the theoretical and experimental results, van der Waals interactions
      and hydrogen bonds were found to play major roles in the binding reaction.
      Furthermore, UV-Vis absorption spectroscopy and synchronous fluorescence spectra
      indicated that the conformation of BSA was changed. The results obtained in the
      work can help understand the action mode between L and its corresponding Eu(III)
      and Tb(III) complexes with BSA, and they are also expected to provide important
      information of designs of new inspired drugs based on Eu and Tb.

PMID- 23000930
TI  - Novel axially disubstituted non-aggregated silicon phthalocyanines.
AB  - This paper describes the synthesis, spectroscopic characterization of a range of
      new axially-disubstituted silicon phthalocyanines with 2-[2
      (dimethylamino)ethoxy] or 2-[2-(1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16
      yl)ethoxy] groups as axial ligands. 2-[2-(Dimethylamino)ethoxy]ethanol 2, 2-[2
      (1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16-yl)ethoxy]ethanol 4 are reacted
      with silicon phthalocyanine 1, to give an axially-disubstituted silicon
      phthalocyanines 3 and 5. Axially-disubstituted silicon phthalocyanine complexes
      were synthesized at the first time. Newly synthesized silicon phthalocyanines
      were characterized by UV-Vis, IR, (1)H NMR, (13)C NMR spectroscopy, ESI mass
      spectrometry. These new silicon(IV) phthalocyanines 3 and 5 showed excellent
      solubility in organic solvents such as CHCl(3), CH(2)Cl(2), acetone, DMF, DMSO,
      THF, EtOAc. The aggregation behavior of these compounds were investigated in
      different concentrations of DMSO. The effect of solvents on absorption spectra
      were studied in various organic solvents. The thermal stabilities of the
      silicon(IV) phthalocyanines 3 and 5 were determined by thermogravimetric
      analysis.

PMID- 23000931
TI  - Molecular structure, electronic property and vibrational spectroscopy of C24
      glycine and Gd@C24-glycine complexes.
AB  - Structure, electronic property and vibrational spectroscopy of C(24)-glycine and
      Gd@C(24)-glycine were systematically explored using the hybrid DFT-B3LYP
      functional. The interaction between empty C(24) cage and the smallest amino acid
      (glycine) was also investigated. It was found that the glycine molecule is
      energetically favorable to interact with the Mid-site on the C(24) cage through
      the amino nitrogen active site, rather than Top-site. The endohedral Gd atom
      increases the volume of the cage by around 6.7-9.8%. Analysis of frontier
      molecular orbitals reveals that the Gd@C(24)-glycine has the low-kinetic
      stability, being consistent with its thermodynamic property reflected by
      dissociation energy. We also see that the VIE and VEA of empty C(24) cage are
      slightly affected by absorbed glycine and endohedral Gd atom. Additionally, the
      assignments of simulated IR spectra are explored. The work may provide a
      theoretical reference for further application related structurally to potential
      antitumour activity.

PMID- 23000937
TI  - Prognostic factors in patients with localized primary cutaneous melanoma.
AB  - The clinical and histopathological characteristics that predict the outcomes of
      patients with melanoma have been studied for more than four decades. Increasingly
      more melanoma patients are being included in prospectively collected databases
      and our understanding of the biology of melanoma is improving. Therefore, the
      melanoma staging system is constantly being revised. The currently valid American
      Joint Committee on Cancer (AJCC) staging system for melanoma has been in place
      since early 2010 and is crucial for the determination of appropriate treatment,
      follow-up, and evaluating the risk of recurrence. Staging of a localized primary
      melanoma is based on the histopathological characteristics of the tumor: Breslow
      tumor thickness, mitotic rate, and presence or absence of ulceration. The Clark
      level of invasion is no longer recommended as a staging criterion. When mitotic
      rate is taken into consideration, it is no longer an independent prognostic
      factor. Other important and independent adverse predictors of primary cutaneous
      melanoma survival that are not part of the AJCC staging system are the age and
      sex of the patient and the anatomic location of the primary tumor. These factors,
      combined with the melanoma's histopathological features, could predict an
      individual patient's prognosis more precisely than the AJCC staging system
      currently in use.

PMID- 23000932
TI  - Selective enrichment of newly synthesized proteins for quantitative secretome
      analysis.
AB  - Secreted proteins constitute a large and biologically important subset of
      proteins that are involved in cellular communication, adhesion and migration. Yet
      secretomes are understudied because of technical limitations in the detection of
      low-abundance proteins against a background of serum-containing media. Here we
      introduce a method that combines click chemistry and pulsed stable isotope
      labeling with amino acids in cell culture to selectively enrich and quantify
      secreted proteins. The combination of these two labeling approaches allows cells
      to be studied irrespective of the complexity of the background proteins. We
      provide an in-depth and differential secretome analysis of various cell lines and
      primary cells, quantifying secreted factors, including cytokines, chemokines and
      growth factors. In addition, we reveal that serum starvation has a marked effect
      on secretome composition. We also analyze the kinetics of protein secretion by
      macrophages in response to lipopolysaccharides.

PMID- 23000933
TI  - The mouse lymph node as an ectopic transplantation site for multiple tissues.
AB  - Cell-based therapy has been viewed as a promising alternative to organ
      transplantation, but cell transplantation aimed at organ repair is not always
      possible. Here we show that the mouse lymph node can support the engraftment and
      growth of healthy cells from multiple tissues. Direct injection of hepatocytes
      into a single mouse lymph node generated enough ectopic liver mass to rescue the
      survival of mice with lethal metabolic disease. Furthermore, thymuses
      transplanted into single lymph nodes of athymic nude mice generated functional
      immune systems that were capable of rejecting allogeneic and xenogeneic grafts.
      Additionally, pancreatic islets injected into the lymph nodes of diabetic mice
      restored normal glucose control. Collectively, these results suggest the
      practical approach of targeting lymph nodes to restore, maintain or improve
      tissue and organ functions.

PMID- 23000938
TI  - Intrinsic skin aging: the role of oxidative stress.
AB  - Skin aging appears to be the result of two overlapping processes, intrinsic and
      extrinsic. It is well accepted that oxidative stress contributes significantly to
      extrinsic skin aging, although findings point towards reactive oxygen species
      (ROS) as one of the major causes of and single most important contributor; not
      only does ROS production increase with age, but human skin cells' ability to
      repair DNA damage steadily decreases over the years. We extrapolated mechanisms
      of intrinsic oxidative stress in tissues other than skin to the skin cells in
      order to provide effective anti-aging strategies and reviewed the literature on
      intrinsic skin aging and the role of oxidative stress.

PMID- 23000939
TI  - Urticarial vasculitis reveals unsuspected thyroiditis.
AB  - A 38-year-old woman presented with erythematous, violaceous plaques with a
      serpiginous and unusual appearance located on the left shoulder, left thigh, and
      right buttock, evolving for 5 days, which eventually became generalized. A skin
      biopsy revealed leukocytoclastic vasculitis and a diagnosis of urticarial
      vasculitis was made. The complete blood count, biochemistry, complement levels,
      and other immunological test results were unremarkable. However, antithyroid
      antibody titers were increased. Despite having normal thyroid function tests and
      an absence of specific symptoms, the patient underwent a thyroid ultrasound,
      which revealed features of thyroiditis, and was subsequently referred to an
      endocrinologist. Several diseases can be associated with urticarial vasculitis,
      namely infections and autoimmune connective-tissue disorders such as systemic
      lupus erythematosus and Sjogren syndrome. Thyroiditis is an uncommon association.

PMID- 23000940
TI  - Erythema nodosum leprosum associated with minocycline.
AB  - Erythema nodosum leprosum is defined by the appearance of tender skin nodules,
      which can be accompanied by fever, joint pain, neuritis, edema, malaise and/or
      lymphadenopathy. The authors describe the case of a 19-year-old Angolan black
      woman, resident in Portugal for the last 10 years, diagnosed with Hansen's
      disease at the age of 12, irregular with follow-up and non-compliant with
      treatment. She was referred to our clinic with painful nodules and pustules on
      the upper limbs, diffuse facial infiltration with pustules and fever, after
      initiating minocycline with the intention of treating acne. Diagnosis of erythema
      nodosum leprosum was confirmed by the presence of acid-fast bacilli in the skin
      smear and also in skin biopsy. Minocycline was suspended and the patient was
      treated with systemic steroids, with prompt clinical improvement. Our case is
      reported to alert clinicians to this unusual presentation of erythema nodosum
      leprosum in a patient treated with highly bactericidal drugs that were not
      intended to treat Hansen's disease.

PMID- 23000941
TI  - An unusual manifestation of a neglected disease.
AB  - We report on a 30-year-old man that was seen by dermatologist for a routine check
      of melanocytic nevi. During the examination he pointed out a lesion on his upper
      back, stating that he did not know how long it had been there. Excision was
      performed and the histopathologic examination showed a dense granulomatous
      infiltrate in the dermis without ulceration. It turned out to be cutaneous
      leishmaniasis, the incidence of which is increasing in our immediate vicinity,
      and therefore it is important to constantly keep it in mind during everyday work
      at the clinic.

PMID- 23000942
TI  - Erythema multiforme as a result of Orf disease.

PMID- 23000943
TI  - Protective effect of diltiazem, a L-type calcium channel antagonist, on
      lysophosphatidylcholine-enhanced hydroxyl radical generation by MPP(+) in rat
      striatum.
AB  - BACKGROUND: The interaction between the PKC and oxygen free radicals. OBJECTIVE
      AND METHODS: The present study examined the effects of lysophosphatidylcholine
      (LPC), an endogenous amphophilic lipid metabolite, on 1-methyl-4-phenylpyridinium
      ion (MPP(+))-induced hydroxyl radical (()OH) generation in rat striatum. LPC (50
      MUM) increased ()OH formation by MPP(+). Further, the effect of diltiazem, a L
      type Ca(2+) channel antagonist, on MPP(+) (5mM)-induced ()OH generation was
      studied. RESULTS: Diltiazem (100 MUM) significantly suppressed LPC and MPP(+)
      induced ()OH generation. The results indicate ()OH generation, and diltiazem may
      have preventive effect on MPP(+)-induced ()OH generation. CONCLUSION: These
      results demonstrated that diltiazem suppressed LPC-induced generation of free
      radical through blockage of Ca(2+) channel in the rat striatum.

PMID- 23000945
TI  - Optoelectronic properties of (ZnO)60 isomers.
AB  - We studied the optoelectronic properties of six possible structures of the
      (ZnO)(60) cluster using density functional theory (DFT). Vertical ionization
      energies and electron affinities are calculated through total energy differences,
      while the optical absorption spectra are obtained by using hybrid time-dependent
      DFT. The (ZnO)(60) cluster has been proven to be particularly stable and it is of
      potential interest for future applications in nanoelectronics, but its ground
      state configuration has been unknown to date. Since the relative stability
      inferred from total energy calculations suffers from a strong dependence on the
      computational scheme adopted, we combined it with optical spectroscopy to
      identify the most abundant geometrical structure of this cluster. The calculated
      optical spectra are different for each isomer and they could be thus used in
      comparison with experimental data to explain the ground state of (ZnO)(60).

PMID- 23000944
TI  - The butyrophilin (BTN) gene family: from milk fat to the regulation of the immune
      response.
AB  - Butyrophilins (BTN) belong to the immunoglobulin (Ig) superfamily of
      transmembrane proteins. These molecules are of increasing interest to
      immunologists, as they share a structural homology with B7 family members at the
      extracellular domain level. Moreover, a role of these molecules has been
      suggested in the negative regulation of lymphocyte activation for almost all the
      BTN that have been studied. In addition, the expression of some BTN family
      members has been reported to be associated with autoimmune diseases. Over the
      last few years, the number of BTN and BTN-like members has greatly increased. In
      this study, the butyrophilin family in mammals has been revisited, using
      phylogenetic analysis to identify all the family members and the phylogenetic
      relations among them, and to establish a standard nomenclature. Fourteen BTN
      groups were identified that are not all conserved between mammalian species. In
      addition, an overview of expression profiles and functional BTN data demonstrates
      that these molecules represent a new area of investigation for the design of
      future strategies in the modulation of the immune system.

PMID- 23000946
TI  - In situ formation of hollow graphitic carbon nanospheres in electrospun amorphous
      carbon nanofibers for high-performance Li-based batteries.
AB  - We report on in situ formation of hollow graphitic carbon nanospheres (HGCNs) in
      amorphous carbon nanofibers (ACNFs) by a combination of electrospinning,
      calcination and acid treatment. The prepared carbon nanofibers contain many HGCNs
      on which defects such as discontinuous graphene sheets with a large d-spacing in
      their wall exist and provide extra sites for Li(+) storage and serve as buffers
      for withstanding large volume expansion and shrinkage during the Li insertion and
      extraction procedure. Furthermore, some exposed HGCNs on the surface of the ACNFs
      as well as hollow structures are favorable for lithium ion diffusion from
      different orientations and sufficient contact between active material and
      electrolyte. In addition, the high conductivity architectures facilitate
      collection and transport of electrons during the cycling process. As a result,
      the ACNFs/HGCNs display a high reversible specific gravimetric capacity of ~750
      mA h g(-1) and volumetric capacity of ~1.1 A h cm(-3) with outstanding rate
      capability and good cycling stability, which is superior to those of carbon
      nanofibers (CNFs), carbon nanotubes (CNTs), porous ACNFs, graphene nanosheets
      (GNSs), GNSs/CNFs, hollow carbon nanospheres and graphite. The synthesis process
      is simple, low-cost and environmentally friendly, providing new avenues for the
      rational engineering of high-energy carbon-based anode materials.

PMID- 23000947
TI  - Step-wise addition of disulfide bridge in firefly luciferase controls color shift
      through a flexible loop: a thermodynamic perspective.
AB  - Multi-color bioluminescence is developed using the introduction of single/double
      disulfide bridges in firefly luciferase. The bioluminescence reaction, which uses
      luciferin, Mg(2+)-ATP and molecular oxygen to yield an electronically excited
      oxyluciferin, is carried out by the luciferase and emits visible light. The
      bioluminescence color of firefly luciferases is determined by the luciferase
      sequence and assay conditions. It has been proposed that the stability of a
      protein may increase through the introduction of a disulfide bridge that
      decreases the configurational entropy of unfolding. Single and double disulfide
      bridges are introduced into Photinus pyralis firefly luciferase to make separate
      mutant enzymes with a single/double bridge (C(81)-A(105)C, L(306)C-L(309)C,
      P(451)C-V(469)C; C(81)-A(105)C/P(451)C-V(469)C, and A(296)C-A(326)C/P(451)C
      V(469)C). By introduction of disulfide bridges using site-directed mutagenesis in
      Photinus pyralis luciferase the color of emitted light was changed to red or kept
      in different extents. The bioluminescence color shift occurred with displacement
      of a critical loop in the luciferase structure without any change in green
      emitter mutants. Thermodynamic analysis revealed that among mutants, L(306)C
      L(309)C shows a remarkable stability against urea denaturation and also a
      considerable increase in kinetic stability and a clear shift in bioluminescence
      spectra towards red.

PMID- 23000948
TI  - Chronically reinforced, operant olfactory conditioning increases the number of
      newborn GABAergic olfactory periglomerular neurons in the adult rat.
AB  - The mammalian brain preserves the ability to replace olfactory periglomerular
      cells (PGC) throughout life. Even though we have detailed a great deal the
      mechanisms underlying stem and amplifying cells maintenance and proliferation, as
      well as those modulating migration and differentiation, our knowledge on PGC
      phenotypic plasticity is at best fragmented and controversial. Here we explored
      whether chronically reinforced olfactory conditioning influences the phenotype of
      newborn PGC. Accordingly, olfactory conditioned rats showed increased numbers of
      GAD 65/67 positive PGC. Because such phenotypic change was not accompanied
      neither by increments in the total number of PGC, or periglomerular cell nuclei
      labeled with bromodeoxyuridine, nor by reductions in the number of tyrosine
      hydroxylase (TH), calbindin (CB) or calretinin (CR) immunoreactive PGC, we
      speculate that increments in the number of GABAergic PGC occur at the expense of
      other PGC phenotypes. In any event, these results support that adult newborn PGC
      phenotype may be subjected to phenotypic plasticity influenced by sensory
      stimulation.

PMID- 23000949
TI  - Prolonged QT interval with T-wave alternans: electrocardiogram-based differential
      diagnosis.

PMID- 23000950
TI  - The expression of intermediate filament protein nestin and its association with
      cyclin-dependent kinase 5 in the glomeruli of rats with diabetic nephropathy.
AB  - BACKGROUND: Podocyte injury plays a crucial role in the development of diabetic
      nephropathy (DN), but its underlying mechanism remains poorly understood.
      Emerging evidences suggest that the cytoskeleton disruption is related to
      podocyte injury. The aim of this study was to investigate whether nestin, a
      cytoskeleton-associated intermediate filament protein, is involved in the
      development of DN. METHODS: Rat diabetes was induced by intraperitoneal injection
      of streptozotocin. The renal histological changes were investigated by light
      microscopy and transmission electron microscopy. The location of nestin and
      vimentin in renal tissues was observed by immunohistochemistry. The protein or
      messenger RNA levels of nestin and cyclin-dependent kinase 5 (Cdk5) were detected
      by Western blot and real-time polymerase chain reaction. The relationship between
      nestin and vimentin was detected by co-immunoprecipitation. RESULTS: Compared
      with controls, diabetic rats showed significant characteristics of renal damage.
      The expression of nestin and vimentin in the glomeruli was increased at the early
      stage of diabetes, which then gradually decreased. Co-immunoprecipitation assays
      demonstrated that nestin disassembled with vimentin in diabetic rats. The
      expression of Cdk5 was increased in a time-dependent manner in diabetic rats. The
      degree of albuminuria in diabetic rats was negatively correlated with nestin and
      positively correlated with Cdk5. Roscovitine, a Cdk5 inhibitor, reduced the
      degradation of nestin. Moreover, podocyte injuries were significantly ameliorated
      by treatment with roscovitine. CONCLUSIONS: The intermediate filament protein
      nestin is associated with development of DN. Blockage of Cdk5 increases the level
      of nestin and attenuates renal damage, which would provide a useful target for DN
      therapy.

PMID- 23000952
TI  - Crystal surface mediated structure transformation of a kinetic framework composed
      of multi-interactive ligand TPHAP and Co(II).
AB  - A tripyridyl multi-interactive ligand TPHAP is prepared by a one-pot reaction on
      a gram scale. Network formation of Co(ii) with TPHAP(-) gave kinetic and
      thermally more stable products. The kinetic network showed an unprecedented
      dynamic network transformation on the crystal surface by a ligand exchange
      reaction.

PMID- 23000953
TI  - Structural modification of sanguinarine and chelerythrine and their in vitro
      acaricidal activity against Psoroptes cuniculi.
AB  - Sanguinarine (1) and chelerythrine (2) are two quaternary benzo[c]phenanthridine
      alkaloids (QBAs). Eighteen derivatives of 1 and 2 were synthesized by
      modification of C=N(+) bond and evaluated for their in vitro acaricidal activity
      against Psoroptes cuniculi, a mange mite. A new method was developed to prepare 6
      alkoxy dihydro derivatives of 1 and 2 (1a-e, 2a-e). Among all the compounds, only
      6-alkoxy dihydrosanguinarines (1a-e) showed significant acaricidal activity at
      5.0 mg/mL and 1a possessed the strongest activity (50% lethal concentrations
      (LC(50))=339.70+/-0.75 mg/L, 50% lethal time (LT(50))=6.53+/-0.04 h), comparable
      with a standard drug ivermectin (LC(50)=168.19+/-11.79 mg/L, LT(50)=16.54+/-0.11
      h). The iminium moiety in 1 and 2 was proven to be the determinant for their
      acaricidal properties. 6-Alkoxy dihydro derivatives (1a-e, 2a-e) were prodrugs of
      1 and 2. Compared with 7,8-dimethoxy groups, 7,8-methylenedioxy group was able to
      significantly improve the bioactivity. The present results suggested that QBAs
      are promising candidates or lead compounds for the development of new
      isoquinoline acaricidal agents.

PMID- 23000955
TI  - The interplay between the intestinal microbiota and the brain.
AB  - The intestinal microbiota consists of a vast bacterial community that resides
      primarily in the lower gut and lives in a symbiotic relationship with the host. A
      bidirectional neurohumoral communication system, known as the gut-brain axis,
      integrates the host gut and brain activities. Here, we describe the recent
      advances in our understanding of how the intestinal microbiota communicates with
      the brain via this axis to influence brain development and behaviour. We also
      review how this extended communication system might influence a broad spectrum of
      diseases, including irritable bowel syndrome, psychiatric disorders and
      demyelinating conditions such as multiple sclerosis.

PMID- 23000956
TI  - Statins, exercise, and skeletal muscle.

PMID- 23000954
TI  - Emerging themes in SecA2-mediated protein export.
AB  - The conserved general secretion (Sec) pathway carries out most protein export in
      bacteria and is powered by the essential ATPase SecA. Interestingly, mycobacteria
      and some Gram-positive bacteria possess two SecA proteins: SecA1 and SecA2. In
      these species, SecA1 is responsible for exporting most proteins, whereas SecA2
      exports only a subset of substrates and is implicated in virulence. However,
      despite the impressive body of knowledge about the canonical SecA1, less is known
      concerning SecA2 function. Here, we review our current understanding of the
      different types of SecA2 systems and outline future directions for their study.

PMID- 23000957
TI  - Effect of statins on skeletal muscle:  exercise, myopathy, and muscle outcomes.
AB  - Statins are effective in reducing low-density lipoprotein cholesterol and cardiac
      events but can produce muscle side effects. We have hypothesized that statin
      related muscle complaints are exacerbated by exercise and influenced by factors
      including mitochondrial dysfunction, membrane disruption, and/or calcium
      handling. The interaction between statins, exercise, and muscle symptoms may be
      more effectively diagnosed and treated as rigorous scientific studies accumulate.

PMID- 23000960
TI  - Increased circulating CD3+/CD31+ T cells in patients with acute coronary
      syndrome.
AB  - The number of circulating endothelial progenitor cells (EPCs) is considered to be
      a surrogate marker for coronary artery disease (CAD). Recent studies have
      identified a novel T-cell subset labeled with CD3(+)/CD31(+), which is necessary
      for EPC colony formation and constitutes the central cluster. However, the
      clinical relevance of the CD3(+)/CD31(+) T cells in CAD remains unclear. We
      sought to clarify whether circulating CD3(+)/CD31(+) T cells are increased in
      patients with acute coronary syndrome (ACS). Circulating CD3(+)/CD31(+) T cells
      were determined in 16 ACS patients undergoing emergency percutaneous coronary
      intervention (PCI) and in 16 control subjects with angiographically normal
      coronary arteries. Although no differences between the groups were found in
      baseline patient characteristics, the ratio of circulating CD3(+)/CD31(+) T cells
      before PCI was higher in ACS patients as compared with that in control subjects
      (51.8 % +/- 7.8 % vs 31.8 % +/- 9.6 %, respectively; P < 0.001). The increased
      ratio of CD3(+)/CD31(+) T cells in ACS patients was not altered 24 h after PCI,
      but became comparable with that in control subjects within 6 months after PCI.
      These results suggest that mobilization of CD3(+)/CD31(+) T cells occurs in ACS,
      but is no longer detectable at 6 months after PCI. 

PMID- 23000961
TI  - Effect of lipo-prostaglandin E1 on cystatin C, beta2-microglobulin, and estimated
      glomerular filtration rate in patients with decompensated heart failure and renal
      dysfunction: a single-center, nonrandomized controlled study.
AB  - A nonrandomized controlled study was conducted to evaluate the effect of lipo
      prostaglandin E1 (lipo-PGE1) on cystatin C (CysC), beta2-microglobulin (B2MG),
      and estimated glomerular filtration rate (eGFR) in patients with decompensated
      heart failure (DHF) and renal dysfunction. A total of 286 enrolled patients with
      DHF and renal dysfunction were nonrandomly assigned a 7-day standard treatment
      without (n = 146) or with (n = 140) lipo-PGE1 intervention. According to the
      baseline eGFR, patients were further classified into mild, moderate, and severe
      renal dysfunction subgroups. By the end of study period, there was no evidence of
      an immense improvement in B2MG, CysC, and eGFR in response to standard treatment
      (all P > 0.05). On the contrary, a noticeable decrease of B2MG and CysC was
      observed in patients receiving lipo-PGE1 intervention, as well as an increase in
      eGFR (all P < 0.05). Moreover, lipo-PGE1 intervention led to greater changes in
      renal function variables from baseline than with standard management (all P <
      0.05). Most important, the favorable renal protective effects of lipo-PGE1 were
      maintained in three subgroups. Lipo-PGE1 intervention brought a substantial
      renoprotective benefit to hospitalized DHF patients as compared with standard
      therapy, suggesting it might offer a promising therapeutic option for the
      management of renal dysfunction associated with DHF. 

PMID- 23000962
TI  - Stimulus-dependent phosphorylation of profilin-1 in angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels, is fundamental to development
      and post-injury tissue repair. Vascular endothelial growth factor (VEGF)-A guides
      and enhances endothelial cell migration to initiate angiogenesis. Profilin-1 (Pfn
      1) is an actin-binding protein that enhances actin filament formation and cell
      migration, but stimulus-dependent regulation of Pfn-1 has not been observed.
      Here, we show that VEGF-A-inducible phosphorylation of Pfn-1 at Tyr 129 is
      critical for endothelial cell migration and angiogenesis. Chemotactic activation
      of VEGF receptor kinase-2 (VEGFR2) and Src induces Pfn-1 phosphorylation in the
      cell leading edge, promoting Pfn-1 binding to actin and actin polymerization.
      Conditional endothelial knock-in of phosphorylation-deficient Pfn1(Y129F) in mice
      reveals that Pfn-1 phosphorylation is critical for angiogenesis in response to
      wounding and ischaemic injury, but not for developmental angiogenesis. Thus,
      VEGFR2/Src-mediated phosphorylation of Pfn-1 bypasses canonical, multistep
      intracellular signalling events to initiate endothelial cell migration and
      angiogenesis, and might serve as a selective therapeutic target for anti
      angiogenic therapy.

PMID- 23000963
TI  - Dll1+ secretory progenitor cells revert to stem cells upon crypt damage.
AB  - Lgr5+ intestinal stem cells generate enterocytes and secretory cells. Secretory
      lineage commitment requires Notch silencing. The Notch ligand Dll1 is expressed
      by a subset of immediate stem cell daughters. Lineage tracing in Dll1(GFP-ires
      CreERT2) knock-in mice reveals that single Dll1(high) cells generate small, short
      lived clones containing all four secretory cell types. Lineage specification thus
      occurs in immediate stem cell daughters through Notch lateral inhibition.
      Cultured Dll1(high) cells form long-lived organoids (mini-guts) on brief Wnt3A
      exposure. When Dll1(high) cells are genetically marked before tissue damage, stem
      cell tracing events occur. Thus, secretory progenitors exhibit plasticity by
      regaining stemness on damage.

PMID- 23000964
TI  - Insm1a-mediated gene repression is essential for the formation and
      differentiation of Muller glia-derived progenitors in the injured retina.
AB  - In zebrafish, retinal injury stimulates Muller glia (MG) reprograming, allowing
      them to generate multipotent progenitors that replace damaged cells and restore
      vision. Recent studies suggest that transcriptional repression may underlie these
      events. To identify transcriptional repressors, we compared the transcriptomes of
      MG and MG-derived progenitors and identified insm1a, a repressor exhibiting a
      biphasic pattern of expression that is essential for retina regeneration. Insm1a
      was found to suppress ascl1a and its own expression, and link injury-dependent
      ascl1a induction with the suppression of the Wnt inhibitor dickkopf (dkk), which
      is necessary for MG dedifferentiation. We also found that Insm1a was responsible
      for sculpting the zone of injury-responsive MG by suppressing hb-egf(a)
      expression. Finally, we provide evidence that Insm1a stimulates progenitor cell
      cycle exit by suppressing a genetic program driving progenitor proliferation. Our
      studies identify Insm1a as a key regulator of retina regeneration and provide a
      mechanistic understanding of how it contributes to multiple phases of this
      process.

PMID- 23000965
TI  - Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15
      ubiquitylation in DNA-damage bypass.
AB  - Protein ubiquitylation has emerged as a key regulatory mechanism in DNA-damage
      signalling and repair pathways. We report a proteome-wide, site-specific survey
      of ubiquitylation changes after ultraviolet irradiation, identifying numerous
      upregulated and downregulated ubiquitylation sites on known components of DNA
      damage signalling, as well as on proteins not previously implicated in this
      process. Our results uncover a critical role for PCNA-associated factor PAF15
      (p15(PAF)/KIAA0101) ubiquitylation during DNA replication. During unperturbed S
      phase, chromatin-associated PAF15 is modified by double mono-ubiquitylation of
      Lys 15 and 24 templated through PCNA binding. Replication blocks trigger rapid,
      proteasome-dependent removal of Lys 15/24-ubiquitylated PAF15 from PCNA,
      facilitating bypass of replication-fork-blocking lesions by allowing recruitment
      of translesion DNA synthesis polymerase poleta to mono-ubiquitylated PCNA at
      stalled replisomes. Our findings demonstrate widespread involvement of ubiquitin
      signalling in genotoxic-stress responses and identify a critical function for
      dynamic PAF15 ubiquitylation in safeguarding genome integrity when DNA
      replication is challenged.

PMID- 23000966
TI  - FIP3-endosome-dependent formation of the secondary ingression mediates ESCRT-III
      recruitment during cytokinesis.
AB  - The final cytokinesis event involves severing of the connecting intercellular
      bridge (ICB) between daughter cells. FIP3-positive recycling endosomes (FIP3
      endosomes) and ESCRT complexes have been implicated in mediating the final stages
      of cytokinesis. Here we analyse the spatiotemporal dynamics of the actin
      cytoskeleton, FIP3-endosome fusion and ESCRT-III localization during cytokinesis
      to show that the ICB narrows by a FIP3-endosome-mediated secondary ingression,
      whereas the ESCRT-III complex is needed only for the last scission step of
      cytokinesis. We characterize the role of FIP3 endosomes during cytokinesis to
      demonstrate that FIP3 endosomes deliver SCAMP2/3 and p50RhoGAP to the ICB during
      late telophase, proteins required for the formation of the secondary ingression.
      We also show that the FIP3-endosome-induced secondary ingression is required for
      the recruitment of the ESCRT-III complex to the abscission site. Finally, we
      characterize a FIP3-endosome-dependent regulation of the ICB cortical actin
      network through the delivery of p50RhoGAP. These results provide a framework for
      the coordinated efforts of actin, FIP3 endosomes and the ESCRTs to regulate
      cytokinesis and abscission.

PMID- 23000967
TI  - Effects of selenium accumulation on phytotoxicity, herbivory, and pollination
      ecology in radish (Raphanus sativus L.).
AB  - Selenium (Se) has contaminated areas in the western USA where pollination is
      critical to the functioning of both agricultural and natural ecosystems, yet we
      know little about how Se can impact pollinators. In a two-year semi-field study,
      the weedy plant Raphanus sativus (radish) was exposed to three selenate
      treatments and two pollination treatments to evaluate the effects on pollinator
      plant interactions. Honey bee (Apis mellifera L.) pollinators were observed to
      readily forage on R. sativus for both pollen and nectar despite high floral Se
      concentrations. Se treatment increased both seed abortion (14%) and decreased
      plant biomass (8-9%). Herbivory by birds and aphids was reduced on Se-treated
      plants, indicating a potential reproductive advantage for the plant. Our study
      sheds light on how pollutants such as Se can impact the pollination ecology of a
      plant that accumulates even moderate amounts of Se.

PMID- 23000968
TI  - Primary investigation on contamination pattern of legacy and emerging halogenated
      organic pollutions in freshwater fish from Liaohe River, Northeast China.
AB  - Legacy halogenated compounds, including polychlorinated biphenyls (PCBs),
      polybrominated diphenyl ethers (PBDEs), and emerging organo-halogen pollutants
      such as Dechlorane Plus (DP), were detected in fish from an old industrial region
      in Northeast China. PCBs and PBDEs were detected in all of the samples, with
      concentrations ranging from 38.15 to 170.51 ng/g lipid weight, and 9.40-39.69
      ng/g lipid weight, respectively. DP was detected in more than 90% of the samples
      with concentrations ranging from not detected (ND) to 470 pg g/g lipid weight.
      Compared with similar data in other areas of the world, PCBs, PBDEs and DP in
      fish from Liaohe River were at medium or low level. An unusually high percentage
      of PCB-209 was first reported in the fish samples collected from China. Other
      halogenated pollutions, such as dichlorodiphenyltrichloroethane (DDT) and its
      metabolites, octachlorostyrene, chlorinated anisole, chlorinated thioanisole,
      triclosan-methyl, and other pesticides, have also been identified in the fish
      samples.

PMID- 23000970
TI  - Microchip electrophoresis with amperometric detection for a novel determination
      of phenolic compounds in olive oil.
AB  - The relevance of the development of microchip electrophoresis applications in the
      field of food analysis is considered in this work. A novel method to determine
      important phenolic compounds in extra virgin olive oil samples using a
      miniaturized chemical analysis system is presented in this paper. Three
      interesting phenolic compounds in olive oil and fruit (tyrosol, hydroxytyrosol
      and oleuropein glucoside) were studied by end-channel amperometric detection
      using a 100 MUm gold wire as working electrode in glass microchip
      electrophoresis. The electrochemical behavior of these compounds was studied and
      the medium to carry out their detection was selected (0.1 M aqueous sulfuric
      acid). The best conditions for the separation were achieved in sodium tetraborate
      (10% methanol, pH 9.50) with different concentrations for the sample and the
      running buffer in order to allow the sample stacking phenomenon. The injection
      was carried out using 600 V for 3 s and the separation voltage was set at 1000 V.
      The quality of the method was evaluated through its analytical figures of merit
      and by its performance on real extra virgin olive oil samples. Determination of
      these compounds was carried out using the standard addition calibration method
      with good recoveries.

PMID- 23000969
TI  - Intraepithelial paracrine Hedgehog signaling induces the expansion of ciliated
      cells that express diverse progenitor cell markers in the basal epithelium of the
      mouse mammary gland.
AB  - The Hedgehog signaling pathway regulates embryo patterning and progenitor cell
      homeostasis in adult tissues, including epidermal appendages. A role for the Hh
      pathway in mammary biology and breast cancer has also been suggested. The aim of
      this study was to analyze Hh signaling in the mouse mammary gland through the
      generation of transgenic mice that express Sonic Hedgehog (Shh) under the control
      of the mammary-specific WAP promoter (WAP-Shh mice). To identify mammary cells
      capable of activating the Hh pathway we bred WAP-Shh mice to Ptch1-lacZ knock-in
      mice, in which the expression of a nuclear-targeted beta-galactosidase reporter
      protein (beta-gal) is driven by the endogenous Patched 1 gene regulatory region.
      After two cycles of induction of transgenic Shh expression, we detected areas of
      X-gal reactivity. Immunohistochemical analysis showed nuclear beta-gal staining
      in clusters of mammary cells in WAP-Shh/Ptch1-lacZ bitransgenic mice. These were
      epithelial cells present in a basal location of displastic ducts and alveoli,
      adjacent to Shh-expressing luminal cells, and overexpressed epithelial basal
      markers keratin 5, 14 and 17 and transcription factor p63. Absence of smooth
      muscle actin expression and a cuboidal morphology differentiated Hh-responding
      cells from flat-shaped mature myoepithelial cells. Groups of cells expressing
      stem cell markers integrin beta3 and keratins 6 and 15 were also detected within
      Hh-responding areas. In addition, we found that Hh-responding cells in the
      mammary glands of WAP-Shh/Ptch1-lacZ mice were ciliated and exhibited a low
      proliferation rate. Our data show the paracrine nature of hedgehog signaling in
      the epithelial compartment of the mouse mammary gland, where a subset of basal
      cells that express mammary progenitor cell markers and exhibit primary cilia is
      expanded in response to secretory epithelium-derived Shh.

PMID- 23000972
TI  - Phosphate mediated adsorption and electron transfer of cytochrome c. A time
      resolved SERR spectroelectrochemical study.
AB  - The study of proteins immobilized on biomimetic or biocompatible electrodes
      represents an active field of research as it pursues both fundamental and
      technological interests. In this context, adsorption and redox properties of
      cytochrome c (Cyt) on different electrode surfaces have been extensively
      reported, although in some cases with contradictory results. Here we report a
      SERR spectroelectrochemical study of the adsorption and electron transfer
      behaviour of the basic protein Cyt on electrodes coated with amino-terminated
      monolayers. The obtained results show that inorganic phosphate (Pi) and ATP
      anions are able to mediate high affinity binding of the protein with preservation
      of the native structure and rendering an average orientation that guarantees
      efficient pathways for direct electron transfer. These findings aid the design of
      Cyt-based bioelectronic devices and understanding the modulation by Pi and ATP of
      physiological functions of Cyt.

PMID- 23000971
TI  - MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and
      JNK pathways.
AB  - Recent studies have identified important roles for microRNAs (miRNAs) in many
      cardiac pathophysiological processes, including the regulation of cardiomyocyte
      hypertrophy. However, the role of miR-350 in the cardiac setting is still
      unclear. The objective of this study is to determine whether miR-350 alone can
      induce pathological cardiac hypertrophy by repressing the SAPK pathway in
      cardiomyocytes. Here we report that miR-350 plays a key role in determining
      pathological cardiomyocyte hypertrophy and apoptosis. Comprehensive microarray
      profiling of miRs and qPCR showed that this unique miRNA was significantly up
      regulated in rat hearts in response to late-stage transverse aortic constriction.
      Western blotting and luciferase assays confirmed that the target mRNAs of miR-350
      are mitogen activated protein kinase (MAPK) 11/14 and MAPK8/9 gene transcripts.
      Gain-of-unction and loss-of-function approaches were used to investigate the
      functional roles of miR-350. The forced over-expression of miR-350 was sufficient
      to induce hypertrophy of cardiomyocytes through the posttranslational suppression
      of p38 and JNK protein synthesis. Moreover, miR-350 led to an increase in
      unphosphorylated NFATc3 and its nuclear translocation, resulting in the over
      expression of pathological hypertrophy markers. As predicted, these effects could
      effectively be imitated by siR-JNK/p38 through the degeneration of p38 and JNK
      mRNAs. Conversely, antagomir-350 could lower the levels of miR-350, reverse the
      expression of target proteins and reduce cell size and apoptosis relative to the
      administration of mutant antagomir-350. Our data provide the first evidence that
      miR-350 is a critical regulator of pathological cardiac hypertrophy and apoptosis
      in rats.

PMID- 23000973
TI  - Oxygen hole doping of nanodiamond.
AB  - Surface-graphitized nanodiamonds (NDs) are promising hybrid nanomaterials which
      appear to combine core properties of diamond with surface properties of graphene
      based materials. Here we demonstrate that NDs covered by graphene islands, so
      called Fullerene-Like Reconstructions (FLRs), are sensitive to hole doping by
      molecular oxygen in water. NDs covered by FLRs (NDs-FLRs) are prepared by
      annealing under vacuum of detonation NDs at 750  degrees C. We propose that
      oxygen hole doping is promoted on FLRs due to a unique electronic interaction
      between the diamond core and the outer graphene layer. As a consequence, NDs-FLRs
      exhibit positive zeta potential in water, unlike NDs surrounded by several
      graphitic layers. Surface hole-doped NDs may be promising nanomaterials for new
      electronic and biomedical applications.

PMID- 23000974
TI  - Dynamic nuclear polarization at 700 MHz/460 GHz.
AB  - We describe the design and implementation of the instrumentation required to
      perform DNP-NMR at higher field strengths than previously demonstrated, and
      report the first magic-angle spinning (MAS) DNP-NMR experiments performed at
      (1)H/e(-) frequencies of 700 MHz/460 GHz. The extension of DNP-NMR to 16.4 T has
      required the development of probe technology, cryogenics, gyrotrons, and
      microwave transmission lines. The probe contains a 460 GHz microwave channel,
      with corrugated waveguide, tapers, and miter-bends that couple microwave power to
      the sample. Experimental efficiency is increased by a cryogenic exchange system
      for 3.2 mm rotors within the 89 mm bore. Sample temperatures <=85 K, resulting in
      improved DNP enhancements, are achieved by a novel heat exchanger design,
      stainless steel and brass vacuum jacketed transfer lines, and a bronze probe
      dewar. In addition, the heat exchanger is preceded with a nitrogen drying and
      generation system in series with a pre-cooling refrigerator. This reduces liquid
      nitrogen usage from >700 l per day to <200 l per day and allows for continuous
      (>7 days) cryogenic spinning without detrimental frost or ice formation. Initial
      enhancements, epsilon=-40, and a strong microwave power dependence suggests the
      possibility for considerable improvement. Finally, two-dimensional spectra of a
      model system demonstrate that the higher field provides excellent resolution,
      even in a glassy, cryoprotecting matrix.

PMID- 23000975
TI  - Preserving the excitation profile of small flip angle RF pulses in the presence
      of rapid transverse relaxation.
AB  - Degradation of excitation profile of selective RF pulses by rapid transverse
      relaxation has been a long-standing concern. In this report we demonstrate that
      transverse relaxation can be incorporated into small flip angle RF pulse design
      based on the linear response theory. Small flip angle pulses that were designed
      without considering transverse relaxation effects can be transformed for a
      predefined pulse duration/T(2) ratio. The transformed pulses, within the realm of
      the linear response theory, produce the same transverse frequency response as if
      there were no relaxation.

PMID- 23000976
TI  - Fast passage dynamic nuclear polarization on rotating solids.
AB  - Magic Angle Spinning (MAS) Dynamic Nuclear Polarization (DNP) has proven to be a
      very powerful way to improve the signal to noise ratio of NMR experiments on
      solids. The experiments have in general been interpreted considering the Solid
      Effect (SE) and Cross-Effect (CE) DNP mechanisms while ignoring the influence of
      sample spinning. In this paper, we show experimental data of MAS-DNP enhancements
      of (1)H and (13)C in proline and SH3 protein in glass forming water/glycerol
      solvent containing TOTAPOL. We also introduce a theoretical model that aims at
      explaining how the nuclear polarization is built in MAS-DNP experiments. By using
      Liouville space based simulations to include relaxation on two simple spin
      models, {electron-nucleus} and {electron-electron-nucleus}, we explain how the
      basic MAS-SE-DNP and MAS-CE-DNP processes work. The importance of fast energy
      passages and short level anti-crossing is emphasized and the differences between
      static DNP and MAS-DNP is explained. During a single rotor cycle the enhancement
      in the {electron-electron-nucleus} system arises from MAS-CE-DNP involving at
      least three kinds of two-level fast passages: an electron-electron dipolar anti
      crossing, a single quantum electron MW encounter and an anti-crossing at the CE
      condition inducing nuclear polarization in- or decrements. Numerical, powder
      averaged, simulations were performed in order to check the influence of the
      experimental parameters on the enhancement efficiencies. In particular we show
      that the spinning frequency dependence of the theoretical MAS-CE-DNP enhancement
      compares favorably with the experimental (1)H and (13)C MAS-DNP enhancements of
      proline and SH3.

PMID- 23000977
TI  - SQUID-sensor-based ultra-low-field MRI calibration with phantom images: towards
      quantitative imaging.
AB  - In ultra-low-field magnetic resonance imaging (ULF MRI), measured resonance
      signals oscillate at Larmor frequencies around 1 kHz compared to even above 100
      MHz in high-field MRI. Thus, detection by induction coils in ULF MRI is not
      feasible, whereas superconducting quantum interference device (SQUID) sensors can
      measure these femtotesla-level signals. The signal-to-noise ratio is enhanced by
      prepolarization in a field that is typically 100-1000 times higher than the field
      during acquisition. Based on both measurements and simulations, a procedure for
      calibrating a SQUID-sensor-based MRI system with MR images is presented in this
      article. Magnetoencephalography (MEG) can be integrated with ULF MRI, and may
      also benefit from such a calibration procedure. Conventionally, electromagnet
      probe signals have been used for the SQUID-sensor calibration in MEG; the
      presented ULF-MRI-based approach using an imaging phantom could replace this
      procedure in hybrid MEG-MRI or ULF MRI alone. The necessary theory is provided
      here with experimental verification. The calibration procedure opens the
      possibility of performing quantitative ULF MRI without sample-specific reference
      scans.

PMID- 23000978
TI  - Dark channel fluorescence observations result from concentration effects rather
      than solvent-solute charge transfer.

PMID- 23000979
TI  - Dips and peaks in fluorescence yield X-ray absorption are due to state-dependent
      decay.

PMID- 23000981
TI  - Knowledge management in chemistry.

PMID- 23000986
TI  - Selective functionalization: Shields for small molecules.

PMID- 23000987
TI  - Chemical virology: Packing polymers in protein cages.

PMID- 23000988
TI  - Molecular simulations: Force fields for carbon capture.

PMID- 23000989
TI  - Main group chemistry: Bonsai phosphorus.

PMID- 23000991
TI  - Selective transformations of complex molecules are enabled by aptameric
      protective groups.
AB  - Emerging trends in drug discovery are prompting a renewed interest in natural
      products as a source of chemical diversity and lead structures. However, owing to
      the structural complexity of many natural compounds, the synthesis of derivatives
      is not easily realized. Here, we demonstrate a conceptually new approach using
      oligonucleotides as aptameric protective groups. These block several
      functionalities by non-covalent interactions in a complex molecule and enable the
      highly chemo- and regioselective derivatization (>99%) of natural antibiotics in
      a single synthetic step with excellent conversions of up to 83%. This technique
      reveals an important structure-activity relationship in neamine-based antibiotics
      and should help both to accelerate the discovery of new biologically active
      structures and to avoid potentially costly and cumbersome synthetic routes.

PMID- 23000990
TI  - Use of the interior cavity of the P22 capsid for site-specific initiation of atom
      transfer radical polymerization with high-density cargo loading.
AB  - Virus-like particles (VLPs) have emerged as important and versatile architectures
      for chemical manipulation in the development of functional hybrid nanostructures.
      Here we demonstrate a successful site-selective initiation of atom-transfer
      radical polymerization reactions to form an addressable polymer constrained
      within the interior cavity of a VLP. Potentially, this protein-polymer hybrid of
      P22 and cross-linked poly(2-aminoethyl methacrylate) could be useful as a new
      high-density delivery vehicle for the encapsulation and delivery of small
      molecule cargos. In particular, the encapsulated polymer can act as a scaffold
      for the attachment of small functional molecules, such as fluorescein dye or the
      magnetic resonance imaging (MRI) contrast agent Gd-diethylenetriaminepentacetate,
      through reactions with its pendant primary amine groups. Using this approach, a
      significant increase in the labelling density of the VLP, compared to that of
      previous modifications of VLPs, can be achieved. These results highlight the use
      of multimeric protein-polymer conjugates for their potential utility in the
      development of VLP-based MRI contrast agents with the possibility of loading
      other cargos.

PMID- 23000992
TI  - Electrode-assisted catalytic water oxidation by a flavin derivative.
AB  - The success of solar fuel technology relies on the development of efficient
      catalysts that can oxidize or reduce water. All molecular water-oxidation
      catalysts reported thus far are transition-metal complexes, however, here we
      report catalytic water oxidation to give oxygen by a fully organic compound, the
      N(5)-ethylflavinium ion, Et-Fl(+). Evolution of oxygen was detected during bulk
      electrolysis of aqueous Et-Fl(+) solutions at several potentials above +1.9 V
      versus normal hydrogen electrode. The catalysis was found to occur on glassy
      carbon and platinum working electrodes, but no catalysis was observed on fluoride
      doped tin-oxide electrodes. Based on spectroelectrochemical results and
      preliminary calculations with density functional theory, one possible mechanistic
      route is proposed in which the oxygen evolution occurs from a peroxide
      intermediate formed between the oxidized flavin pseudobase and the oxidized
      carbon electrode. These findings offer an organic alternative to the traditional
      water-oxidation catalysts based on transition metals.

PMID- 23000993
TI  - Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific
      fluorogenic probe.
AB  - Early diagnosis of tuberculosis can dramatically reduce both its transmission and
      the associated death rate. The extremely slow growth rate of the causative
      pathogen, Mycobacterium tuberculosis (Mtb), however, makes this challenging at
      the point of care, particularly in resource-limited settings. Here we report the
      use of BlaC (an enzyme naturally expressed/secreted by tubercle bacilli) as a
      marker and the design of BlaC-specific fluorogenic substrates as probes for Mtb
      detection. These probes showed an enhancement by 100-200 times in fluorescence
      emission on BlaC activation and a greater than 1,000-fold selectivity for BlaC
      over TEM-1 beta-lactamase, an important factor in reducing false-positive
      diagnoses. Insight into the BlaC specificity was revealed by successful co
      crystallization of the probe/enzyme mutant complex. A refined green fluorescent
      probe (CDG-OMe) enabled the successful detection of live pathogen in less than
      ten minutes, even in unprocessed human sputum. This system offers the opportunity
      for the rapid, accurate detection of very low numbers of Mtb for the clinical
      diagnosis of tuberculosis in sputum and other specimens.

PMID- 23000994
TI  - Ab initio carbon capture in open-site metal-organic frameworks.
AB  - During the formation of metal-organic frameworks (MOFs), metal centres can
      coordinate with the intended organic linkers, but also with solvent molecules. In
      this case, subsequent activation by removal of the solvent molecules creates
      unsaturated 'open' metal sites known to have a strong affinity for CO(2)
      molecules, but their interactions are still poorly understood. Common force
      fields typically underestimate by as much as two orders of magnitude the
      adsorption of CO(2) in open-site Mg-MOF-74, which has emerged as a promising MOF
      for CO(2) capture. Here we present a systematic procedure to generate force
      fields using high-level quantum chemical calculations. Monte Carlo simulations
      based on an ab initio force field generated for CO(2) in Mg-MOF-74 shed some
      light on the interpretation of thermodynamic data from flue gas in this material.
      The force field describes accurately the chemistry of the open metal sites, and
      is transferable to other structures. This approach may serve in molecular
      simulations in general and in the study of fluid-solid interactions.

PMID- 23000996
TI  - Visualization of hierarchically structured zeolite bodies from macro to nano
      length scales.
AB  - A major challenge in the implementation of laboratory-designed catalysts is the
      scale-up into technically relevant forms. Advanced characterization is essential
      to understand and optimize catalyst assembly and function in industrial reactors.
      This Article presents an integrated approach to visualizing millimetre-sized
      extrudates and granules of a hierarchical MFI-type zeolite, displaying trimodal
      networks of micropores (0.56 nm), intracrystalline mesopores (~10 nm) and
      macropores (~200-300 nm). As exemplified for the conversion of methanol to
      olefins, the hierarchical zeolite yields a superior performance compared to its
      conventional analogue. The combination of dedicated specimen preparation with
      state-of-the-art optical, X-ray and electron-based microscopic and tomographic
      techniques proves a powerful methodology to reveal otherwise inaccessible
      information regarding structural organization over the whole range of length
      scales. It is expected that these tools will play a crucial role in the
      rationalization of scale-up principles in catalyst development.

PMID- 23000995
TI  - Thiourea-catalysed ring opening of episulfonium ions with indole derivatives by
      means of stabilizing non-covalent interactions.
AB  - Small organic and metal-containing molecules (molecular mass <1,000) can catalyse
      synthetically useful reactions with the high levels of stereoselectivity
      typically associated with macromolecular enzymatic catalysts. Whereas enzymes are
      generally understood to accelerate reactions and impart selectivity as they
      stabilize specific transition structures through networks of cooperative
      interactions, enantioselectivity with chiral, small-molecule catalysts is
      rationalized typically by the steric destabilization of all but one dominant
      pathway. However, it is increasingly apparent that stabilizing effects also play
      an important role in small-molecule catalysis, although the mechanistic
      characterization of such systems is rare. Here, we show that arylpyrrolidino
      amido thiourea catalysts catalyse the enantioselective nucleophilic ring opening
      of episulfonium ions by indoles. Evidence is provided for the selective
      transition-state stabilization of the major pathway by the thiourea catalyst in
      the rate- and selectivity-determining step. Enantioselectivity is achieved
      through a network of attractive anion binding, cation-pi and hydrogen-bond
      interactions between the catalyst and the reacting components in the transition
      structure assembly.

PMID- 23000997
TI  - Submicrometre geometrically encoded fluorescent barcodes self-assembled from DNA.
AB  - The identification and differentiation of a large number of distinct molecular
      species with high temporal and spatial resolution is a major challenge in
      biomedical science. Fluorescence microscopy is a powerful tool, but its
      multiplexing ability is limited by the number of spectrally distinguishable
      fluorophores. Here, we used (deoxy)ribonucleic acid (DNA)-origami technology to
      construct submicrometre nanorods that act as fluorescent barcodes. We demonstrate
      that spatial control over the positioning of fluorophores on the surface of a
      stiff DNA nanorod can produce 216 distinct barcodes that can be decoded
      unambiguously using epifluorescence or total internal reflection fluorescence
      microscopy. Barcodes with higher spatial information density were demonstrated
      via the construction of super-resolution barcodes with features spaced by ~40 nm.
      One species of the barcodes was used to tag yeast surface receptors, which
      suggests their potential applications as in situ imaging probes for diverse
      biomolecular and cellular entities in their native environments.

PMID- 23000998
TI  - The energy barrier in singlet fission can be overcome through coherent coupling
      and entropic gain.
AB  - One strategy to improve solar-cell efficiency is to generate two excited
      electrons from just one photon through singlet fission, which is the conversion
      of a singlet (S(1)) into two triplet (T(1)) excitons. For efficient singlet
      fission it is believed that the cumulative energy of the triplet states should be
      no more than that of S(1). However, molecular analogues that satisfy this
      energetic requirement do not show appreciable singlet fission, whereas
      crystalline tetracene displays endothermic singlet fission with near-unity
      quantum yield. Here we probe singlet fission in tetracene by directly following
      the intermediate multiexciton (ME) state. The ME state is isoenergetic with 2 *
      T(1), but fission is not activated thermally. Rather, an S(1) <=> ME
      superposition formed through a quantum-coherent process allows access to the
      higher-energy ME. We attribute entropic gain in crystalline tetracene as the
      driving force for the subsequent decay of S(1) <=> ME into 2 * T(1), which leads
      to a high singlet-fission yield.

PMID- 23000999
TI  - Label-free measuring and mapping of binding kinetics of membrane proteins in
      single living cells.
AB  - Membrane proteins mediate a variety of cellular responses to extracellular
      signals. Although membrane proteins are studied intensively for their values as
      disease biomarkers and therapeutic targets, in situ investigation of the binding
      kinetics of membrane proteins with their ligands has been a challenge.
      Traditional approaches isolate membrane proteins and then study them ex situ,
      which does not reflect accurately their native structures and functions. We
      present a label-free plasmonic microscopy method to map the local binding
      kinetics of membrane proteins in their native environment. This analytical method
      can perform simultaneous plasmonic and fluorescence imaging, and thus make it
      possible to combine the strengths of both label-based and label-free techniques
      in one system. Using this method, we determined the distribution of membrane
      proteins on the surface of single cells and the local binding kinetic constants
      of different membrane proteins. Furthermore, we studied the polarization of the
      membrane proteins on the cell surface during chemotaxis.

PMID- 23001000
TI  - Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated
      free radical reactions.
AB  - Radical reactions are a powerful class of chemical transformations. However, the
      formation of radical species to initiate these reactions has often required the
      use of stoichiometric amounts of toxic reagents, such as tributyltin hydride.
      Recently, the use of visible-light-mediated photoredox catalysis to generate
      radical species has become popular, but the scope of these radical precursors has
      been limited. Here, we describe the identification of reaction conditions under
      which photocatalysts such as fac-Ir(ppy)3 can be utilized to form radicals from
      unactivated alkyl, alkenyl and aryl iodides. The generated radicals undergo
      reduction via hydrogen atom abstraction or reductive cyclization. The reaction
      protocol utilizes only inexpensive reagents, occurs under mild reaction
      conditions, and shows exceptional functional group tolerance. Reaction efficiency
      is maintained upon scale-up and decreased catalyst loading, and the reaction time
      can be significantly shortened when the reaction is performed in a flow reactor.

PMID- 23001002
TI  - A touch of indium.

PMID- 23001003
TI  - Congruency and responsiveness of perceived exertion and time-to-end-point during
      an intermittent isometric fatigue task.
AB  - The aims of this study were (1) to investigate the relationship between self
      perception of effort and task duration in an intermittent isometric fatigue trial
      (IIF) and (2) to evaluate the capability of two assessment paradigms (perceived
      exertion; perceived task duration) to reflect changes in IIF intensity. Fifteen
      participants performed two IIF tasks of the knee extensors at intensities of 60
      and 70 % of daily peak force, each separated by 48-72 h. Ordering of the tasks
      was counter-balanced and participants were blinded to the precise intensity of
      each IIF. A category-ratio scale (CR-10) and visual analogue scale were used
      during each IIF task to record measures of perceived exertion and perceived task
      duration, respectively. Measures were recorded at 10 % intervals across the
      relative duration of each IIF task. Pearson product-moment correlation
      coefficients revealed strong positive correlations (r > 0.99; p < 0.01) between
      completed task duration and both perceptual scales at the two IIF intensities.
      Separate two-way repeated measures ANOVAs of CR-10 and perceived task duration
      responses revealed significant main effects for time only (F [2.2,30.1] = 126.8;
      p < 0.001; F [2.6,36.8] = 117.2; p < 0.001, CR-10 and perceived task duration,
      respectively). The results suggest that perceived exertion and perceived task
      duration are equally effective predictors of IIF end-point. However, neither
      measure was sufficiently responsive to discriminate between 10 % changes in
      exercise intensity.

PMID- 23001004
TI  - A biphasic pulling force acts on transmembrane helices during translocon-mediated
      membrane integration.
AB  - Membrane proteins destined for insertion into the inner membrane of bacteria or
      the endoplasmic reticulum membrane in eukaryotic cells are synthesized by
      ribosomes bound to the bacterial SecYEG or the homologous eukaryotic Sec61
      translocon. During co-translational membrane integration, transmembrane alpha
      helical segments in the nascent chain exit the translocon through a lateral gate
      that opens toward the surrounding membrane, but the mechanism of lateral exit is
      not well understood. In particular, little is known about how a transmembrane
      helix behaves when entering and exiting the translocon. Using translation-arrest
      peptides from bacterial SecM proteins and from the mammalian Xbp1 protein as
      force sensors, we show that substantial force is exerted on a transmembrane helix
      at two distinct points during its transit through the translocon channel,
      providing direct insight into the dynamics of membrane integration.

PMID- 23001005
TI  - The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.
AB  - The human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3
      (APOBEC3, referred to as A3) proteins are cellular cytidine deaminases that
      potently restrict retrovirus replication. However, HIV-1 viral infectivity factor
      (Vif) counteracts the antiviral activity of most A3 proteins by targeting them
      for proteasomal degradation. To date, the structure of an A3 protein containing a
      Vif-binding interface has not been solved. Here, we report a high-resolution
      crystal structure of APOBEC3C and identify the HIV-1 Vif-interaction interface.
      Extensive structure-guided mutagenesis revealed the role of a shallow cavity
      composed of hydrophobic or negatively charged residues between the alpha2 and
      alpha3 helices. This region is distant from the DPD motif (residues 128-130) of
      APOBEC3G that participates in HIV-1 Vif interaction. These findings provide
      insight into Vif-A3 interactions and could lead to the development of new
      pharmacologic anti-HIV-1 compounds.

PMID- 23001006
TI  - Structural basis of fibrillar collagen trimerization and related genetic
      disorders.
AB  - The C propeptides of fibrillar procollagens have crucial roles in tissue growth
      and repair by controlling both the intracellular assembly of procollagen
      molecules and the extracellular assembly of collagen fibrils. Mutations in C
      propeptides are associated with several, often lethal, genetic disorders
      affecting bone, cartilage, blood vessels and skin. Here we report the crystal
      structure of a C-propeptide domain from human procollagen III. It reveals an
      exquisite structural mechanism of chain recognition during intracellular
      trimerization of the procollagen molecule. It also gives insights into why some
      types of collagen consist of three identical polypeptide chains, whereas others
      do not. Finally, the data show striking correlations between the sites of
      numerous disease-related mutations in different C-propeptide domains and the
      degree of phenotype severity. The results have broad implications for
      understanding genetic disorders of connective tissues and designing new
      therapeutic strategies.

PMID- 23001007
TI  - Reduction of furan derivatives by overexpressing NADH-dependent Adh1 improves
      ethanol fermentation using xylose as sole carbon source with Saccharomyces
      cerevisiae harboring XR-XDH pathway.
AB  - Several alcohol dehydrogenase (ADH)-related genes have been identified as enzymes
      for reducing levels of toxic compounds, such as, furfural and/or 5
      hydroxymethylfurfural (5-HMF), in hydrolysates of pretreated lignocelluloses. To
      date, overexpression of these ADH genes in yeast cells have aided ethanol
      production from glucose or glucose/xylose mixture in the presence of furfural or
      5-HMF. However, the effects of these ADH isozymes on ethanol production from
      xylose as a sole carbon source remain uncertain. We showed that overexpression of
      mutant NADH-dependent ADH1 derived from TMB3000 strain in the recombinant
      Saccharomyces cerevisiae, into which xylose reductase (XR) and xylitol
      dehydrogenase (XDH) pathway of Pichia stipitis has been introduced, improved
      ethanol production from xylose as a sole carbon source in the presence of 5-HMF.
      Enhanced furan-reducing activity is able to regenerate NAD(+) to relieve redox
      imbalance, resulting in increased ethanol yield arising from decreased xylitol
      accumulation. In addition, we found that overexpression of wild-type ADH1
      prevented the more severe inhibitory effects of furfural in xylose fermentation
      as well as overexpression of TMB3000-derived mutant. After 120 h of fermentation,
      the recombinant strains overexpressing wild-type and mutant ADH1 completely
      consumed 50 g/L xylose in the presence of 40 mM furfural and most efficiently
      produced ethanol (15.70 g/L and 15.24 g/L) when compared with any other test
      conditions. This is the first report describing the improvement of ethanol
      production from xylose as the sole carbon source in the presence of furan
      derivatives with xylose-utilizing recombinant yeast strains via the
      overexpression of ADH-related genes.

PMID- 23001008
TI  - Characterization of a novel lipolytic enzyme from Aspergillus oryzae.
AB  - In this study, we report the characterization of a protein from Aspergillus
      oryzae, exhibiting sequence identity with paraben esterase from the genus
      Aspergillus. The coding region of 1,586 bp, including a 77-bp intron, encoded a
      protein of 502 amino acids. The gene without the signal peptide of 19 amino acids
      was cloned into a vector, pPICZalphaC, and expressed successfully in Pichia
      pastoris as an active extracellular protein. The purified recombinant protein had
      pH and temperature optima of 7.0-8.0 and 30  degrees C, respectively, and was
      stable at the pH range of 7.0-10.0 and up to 40  degrees C. The optimal substrate
      for hydrolysis by the purified recombinant protein, among a panel of alpha
      naphthyl esters (C2-C16), was alpha-naphthyl butyrate (C4), with activity of 0.16
      units/mg protein. The considerable hydrolytic activity of the purified
      recombinant enzyme toward tributyrin was determined. However, no paraben esterase
      activity was detected toward the ethyl, propyl, and butyl esters of 4
      hydroxybenzoic acid. In addition, no activity was detected toward the methyl
      esters of ferulic, p-coumaric, caffeic, and sinapic acids that would indicate
      feruloyl esterase activity.

PMID- 23001009
TI  - Improving the thermostability of methyl parathion hydrolase from Ochrobactrum sp.
      M231 using a computationally aided method.
AB  - Good protein thermostability is very important for the protein application. In
      this report, we propose a strategy which contained a prediction method to select
      residues related to protein thermal stability, but not related to protein
      function, and an experiment method to screen the mutants with enhanced
      thermostability. The prediction strategy was based on the calculated site
      evolutionary entropy and unfolding free energy difference between the mutant and
      wild-type (WT) methyl parathion hydrolase enzyme from Ochrobactrum sp. M231 [Ochr
      methyl parathion hydrolase (MPH)]. As a result, seven amino acid sites within
      Ochr-MPH were selected and used to construct seven saturation mutagenesis
      libraries. The results of screening these libraries indicated that six sites
      could result in mutated enzymes exhibiting better thermal stability than the WT
      enzyme. A stepwise evolutionary approach was designed to combine these selected
      mutants and a mutant with four point mutations (S274Q/T183E/K197L/S192M) was
      selected. The Tm and T50 of the mutant enzyme were 11.7 and 10.2  degrees C
      higher, respectively, than that of the WT enzyme. The success of this design
      methodology for Ochr-MPH suggests that it was an efficient strategy for enhancing
      protein thermostability and suitable for protein engineering.

PMID- 23001010
TI  - Erratum to: Identification of functional differences between recombinant human
      alpha and beta cardiac myosin motors.
AB  - The myosin isoform composition of the heart is dynamic in health and disease and
      has been shown to affect contractile velocity and force generation. While
      different mammalian species express different proportions of alpha and beta
      myosin heavy chain, healthy human heart ventricles express these isoforms in a
      ratio of about 1:9 (alpha:beta) while failing human ventricles express no
      detectable alpha-myosin. We report here fast-kinetic analysis of recombinant
      human alpha and beta myosin heavy chain motor domains. This represents the first
      such analysis of any human muscle myosin motor and the first of alpha-myosin from
      any species. Our findings reveal substantial isoform differences in individual
      kinetic parameters, overall contractile character, and predicted cycle times. For
      these parameters, alpha-subfragment 1 (S1) is far more similar to adult fast
      skeletal muscle myosin isoforms than to the slow beta isoform despite 91%
      sequence identity between the motor domains of alpha- and beta-myosin. Among the
      features that differentiate alpha- from beta-S1: the ATP hydrolysis step of alpha
      S1 is ~ten-fold faster than beta-S1, alpha-S1 exhibits ~five-fold weaker actin
      affinity than beta-S1, and actin.alpha-S1 exhibits rapid ADP release, which is
      >ten-fold faster than ADP release for beta-S1. Overall, the cycle times are ten
      fold faster for alpha-S1 but the portion of time each myosin spends tightly bound
      to actin (the duty ratio) is similar. Sequence analysis points to regions that
      might underlie the basis for this finding.

PMID- 23001011
TI  - Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells.
AB  - Hypermethylation of SOCS genes is associated with many human cancers, suggesting
      a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS
      proteins modulate turnover of numerous target proteins. Few SOCS targets
      identified so far have a direct role in cell cycle progression; the mechanism by
      which SOCS regulate the cell cycle thus remains largely unknown. Here we show
      that SOCS1 overexpression inhibits in vitro and in vivo expansion of human
      melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its
      degradation by the proteasome. Cells therefore show a G1/S transition defect, as
      well as a secondary blockade in mitosis and accumulation of cells in metaphase.
      SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase
      in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the
      G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells
      accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in
      mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These
      observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression,
      suggesting this molecule as a candidate for the design of new therapeutic
      strategies for human melanoma.

PMID- 23001012
TI  - Nanobody-induced perturbation of LFA-1/L-plastin phosphorylation impairs MTOC
      docking, immune synapse formation and T cell activation.
AB  - The T cell integrin receptor LFA-1 orchestrates adhesion between T cells and
      antigen-presenting cells (APCs), resulting in formation of a contact zone known
      as the immune synapse (IS) which is supported by the cytoskeleton. L-plastin is a
      leukocyte-specific actin bundling protein that rapidly redistributes to the
      immune synapse following T cell-APC engagement. We used single domain antibodies
      (nanobodies, derived from camelid heavy-chain only antibodies) directed against
      functional and structural modules of L-plastin to investigate its contribution to
      formation of an immune synapse between Raji cells and human peripheral blood
      mononuclear cells or Jurkat T cells. Nanobodies that interact either with the EF
      hands or the actin binding domains of L-plastin both trapped L-plastin in an
      inactive conformation, causing perturbation of IS formation, MTOC docking towards
      the plasma membrane, T cell proliferation and IL-2 secretion. Both nanobodies
      delayed Ser(5) phosphorylation of L-plastin which is required for enhanced
      bundling activity. Moreover, one nanobody delayed LFA-1 phosphorylation, reduced
      the association between LFA-1 and L-plastin and prevented LFA-1 enrichment at the
      IS. Our findings reveal subtle mechanistic details that are difficult to attain
      by conventional means and show that L-plastin contributes to immune synapse
      formation at distinct echelons.

PMID- 23001013
TI  - Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1
      and GLUT-3 in diabetic rats: effect of pyridoxine treatment.
AB  - The incidence of type 2 diabetes mellitus is rising at alarming proportions.
      Central nervous system plays an important part in orchestrating glucose
      metabolism, with accumulating evidence linking dysregulated central nervous
      system circuits to the failure of normal glucoregulatory mechanisms. Pyridoxine
      is a water soluble vitamin and it has important role in brain function. This
      study aims to evaluate the role of pyridoxine in striatal glucose regulation
      through dopaminergic receptor expressions in streptozotocin induced diabetic
      rats. Radio receptor binding assays for dopamine D(1), D(2) receptors were done
      using [(3)H] 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol and
      [(3)H] 5-chloro-2-methoxy-4-methylamino-N-[-2-methyl-1-(phenylmethyl)pyrrolidin-3
      yl]benzamide. Gene expressions were done using fluorescently labeled Taqman
      probes of dopamine D(1), D(2) receptor, Insulin receptor, Insulin like growth
      factor-1(IGF-1) and Glucose transporter-3 (GLUT-3). Bmax of dopamine D(1)
      receptor is decreased and B(max) of dopamine D(2) was increased in diabetic rats
      compared to control. Gene expression of dopamine D(1) receptor was down regulated
      and dopamine D(2) receptor was up regulated in diabetic rats. Our results showed
      decreased gene expression of Insulin receptor, IGF-1 and increased gene
      expression of GLUT-3 in diabetic rats compared to control. Pyridoxine treatment
      restored diabetes induced alterations in dopamine D(1), D(2) receptors, Insulin
      receptor, IGF-1, GLUT-3 gene expressions in striatum compared to diabetic rats.
      Insulin treatment reversed dopamine D(1), D(2) receptor, GLUT-3 mRNA expression,
      D(2) receptor binding parameters in the striatum compared to diabetic group. Our
      results suggest the potential role of pyridoxine supplementation in ameliorating
      diabetes mediated dysfunctions in striatal dopaminergic receptor expressions and
      insulin signaling. Thus pyridoxine has therapeutic significance in diabetes
      management.

PMID- 23001014
TI  - Cisplatin causes over-expression of tachykinin NK(1) receptors and increases
      ERK1/2- and PKA- phosphorylation during peak immediate- and delayed-phase emesis
      in the least shrew (Cryptotis parva) brainstem.
AB  - Scant information is available regarding the effects of cisplatin on the
      expression profile of tachykinin NK(1) receptors and downstream signaling during
      cisplatin-induced emesis. Cisplatin causes peak early- and delayed-phase emesis
      in the least shrew at 1-2 and 33 h post-injection. To investigate the expression
      profile of NK(1) receptor during both emetic phases, we cloned the cDNA
      corresponding to a ~700 base pairs of mRNA flanked by two stretches of
      nucleotides conserved among different species and demonstrated that the shrew
      NK(1) receptor nucleotide sequence shares ~90% sequence identity with the human
      NK(1) receptor. Of the 12 time-points tested, significant increases in expression
      levels of NK(1) receptor mRNA in the shrew brainstem occurred at 2 and 28 h post
      cisplatin injection, whereas intestinal NK(1) receptor mRNA was increased at 28
      h. Shrew brainstem and intestinal substance P mRNA levels also tended to increase
      during the two phases. Furthermore, expression levels of NK(1) receptor protein
      were significantly increased in the brainstem at 2, 8, and 33 h post-cisplatin.
      No change in brainstem 5-HT(3) receptor protein expression was observed. The
      temporal enhancements in NK(1) receptor protein expression were mirrored by
      significant increases in the phosphorylation status of the brainstem ERK1/2 at 2,
      8, and 33 h post-cisplatin. Phosphorylation of PKA significantly increased at
      33rd and 40th hour. Our results indicate associations between cisplatin's peak
      immediate- and delayed-phase vomiting frequency with increased: (1) expression
      levels of NK(1) receptor mRNA and its protein level, and (2) downstream NK(1)
      receptor-mediated phosphorylation of ERK1/2 and PKA signaling.

PMID- 23001015
TI  - Effect of synthetic eel calcitonin, elcatonin, on cold and mechanical allodynia
      induced by oxaliplatin and paclitaxel in rats.
AB  - Oxaliplatin and paclitaxel are commonly used anti-cancer drugs, but they
      frequently cause peripheral neuropathic pain. In this study, we investigated the
      effect of elcatonin, a synthetic eel calcitonin, on oxaliplatin- and paclitaxel
      induced neuropathy in rats. The rats were treated with a single dose of
      oxaliplatin (6 mg/kg, i.p.) or repeated doses of paclitaxel (2 mg/kg, i.p.) on 4
      alternate days. Both treatments resulted in cold and mechanical allodynia. We
      assessed the anti-allodynic effects of subcutaneously administered elcatonin (20
      U/kg/day) by using a newly developed method to provide cold stimulation (8
      degrees C) directly to the hind paw of the rats and by using the von Frey test.
      Elcatonin almost completely reversed the effects of both cold and mechanical
      allodynia. To determine the mechanism of this anti-allodynic effect, we examined
      the effect of elcatonin on neuropathy induced by intraplantar injection of two
      organic compounds: allyl isothiocyanate (1 nmol/paw), which activates transient
      receptor potential ankyrin-1 channels, and menthol (1.28 MUmol/paw), which
      activates transient receptor potential ankyrin-1 and melastatin-8. Pre
      administration of elcatonin almost completely prevented cold and mechanical
      allodynia from being induced by both compounds. These results suggest that
      elcatonin attenuates oxaliplatin- and paclitaxel-induced neuropathic pain by
      inhibiting the cellular signaling related to transient receptor potential ankyrin
      1 and melastatin-8. Thus, we conclude that administration of elcatonin may
      improve the quality of life of cancer patients receiving chemotherapy.

PMID- 23001016
TI  - Arguments for an increasing differentiation towards fibrocartilaginous components
      in midportion Achilles tendinopathy.
AB  - PURPOSE: The objective of this study was to investigate the fibrocartilaginous
      differentiation occurring in midportion Achilles tendinopathy. METHODS: Tendon
      samples were retrospectively collected from 23 patients, who had undergone
      surgery for midportion Achilles tendinopathy resistant to conservative treatment.
      Based on histological scores, the biopts were subdivided into three categories: a
      light, moderate and severe histopathological stage. Throughout these stages,
      immunohistochemical staining was performed against biglycan, aggrecan and
      collagen type II, components characteristic for fibrocartilage. Staining of these
      components was evaluated using a semi-quantitative scoring method. RESULTS: The
      immunohistochemical scores of biglycan and aggrecan were statistically
      significant between the histopathological stages (P < 0.001). The
      immunohistochemical scores were positively correlated with the increasing
      histopathological stages [Spearman's correlation coefficient = 0.93 for biglycan
      and 0.78 for aggrecan (P < 0.001)]. Staining for collagen type II remained
      negative throughout these stages. CONCLUSION: Immunohistochemical staining of the
      fibrocartilaginous components biglycan and aggrecan showed a progressive
      increase, correlated with a further evolved histopathological stage. This
      observation gave arguments for an increased differentiation towards
      fibrocartilaginous components at protein level in midportion Achilles
      tendinopathy.

PMID- 23001017
TI  - Reverse gracilis muscle flap: an alternative means of skin coverage for recurrent
      infection after TKA.
AB  - PURPOSE: Poor wound-healing and skin necrosis are serious but not unusual
      complications after total knee arthroplasty, and when skin or soft tissue
      necrosis occurs, reconstructions in the knee area need thin, pliable, tough skin
      flaps. METHODS: A 62-year-old man, who previously underwent multiple TKR
      operations due to recurrent infection, was transferred from another hospital
      after a gastrocnemius muscle rotation flap failed. We decided to treat the
      affected area with a reverse gracilis muscle flap. After confirming that the
      secondary pedicle was intact by Doppler sonography, muscle dissection was
      extended to the entry of the secondary pedicle. The proximal tendon of the
      gracilis muscle was transected, and the muscle was rotated 180 degrees  and
      placed at the recipient site. RESULTS: The aim is to report a case of
      reconstruction at the anterior knee using a reverse gracilis muscle flap that
      achieved an excellent final clinical result. CONCLUSION: This case suggests that
      the indications for a reverse gracilis muscle flap could be broadened when other
      flaps are not available for knee prosthesis coverage.

PMID- 23001018
TI  - Stroke and thromboembolism in atrial fibrillation.
AB  - We performed a systematic review of the available evidence on the relationship
      between the individual clinical, echocardiographic and laboratory characteristics
      of patients with atrial fibrillation (AF) and the risk of stroke. A systematic
      review was also performed of all published stroke risk stratification models, as
      well as the accuracy of their discriminative ability between risk strata. Third,
      we reviewed the literature on cost-effectiveness analyses with oral
      anticoagulation in AF. From the systematic review on stroke risk factors, a prior
      stroke or transient ischemic attack (15/16 studies positive, risk ratio [RR]
      2.86), hypertension (11/20 studies positive, RR 2.27), aging (9/13 studies
      positive, RR 1.46 per decade increase), structural heart disease (9/13 studies
      positive, RR 2.0) and diabetes (9/14 studies positive, RR 1.62) were found to be
      good independent predictors of stroke. Supportive evidence was found for sex
      (8/22 studies positive, RR 1.67), vascular disease (6/17 studies positive, RR
      2.61) and heart failure (7/18 studies positive, RR 1.85). The various risk
      stratification schemes classified variable proportions as low, moderate and high
      risk, but the CHA(2)DS(2)-VASc score classified the smallest proportion of
      patients as 'low risk'. Anticoagulation with vitamin K antagonists and dabigatran
      is cost-effective in patients at high risk of stroke, but not in patients without
      any other stroke risk factor beside AF. Continued efforts are warranted to
      improve the antithrombotic management of AF patients to identify, and challenge,
      risk factors and refine risk stratification models in order to realize an
      individualized tailored, risk factor-based approach.

PMID- 23001019
TI  - Proton-pump inhibitors could be innocent when used concomitantly with
      clopidogrel.

PMID- 23001020
TI  - Keratoconus in a case of lipoid proteinosis.
AB  - PURPOSE: To report a patient of lipoid proteinosis (LP) with bilateral
      keratoconus. METHODS: A 16-year-old boy presented to our institution with a
      complaint of gradual decrease in vision over the past 4 years in both eyes and a
      contact lens intolerance. He had a hoarse voice and multiple areas of
      hyperpigmented lesions over the head and neck region. Slit lamp biomicroscopy of
      the both eyes showed multiple round solid pearly lesions along the upper and
      lower lid margins and a mild central corneal ectasia in both eyes. Central
      corneal thickness and the keratometric values were measured by using Scheimpflug
      imaging (Pentacam), and the results were compatible with keratoconus. The
      histopathologic examination of the lesions taken from bilateral eyelid margins
      showed hyalinosis, papillomatosis, and depositions of eosinophilic material
      around the blood vessels, which were compatible with LP. CONCLUSIONS: With this
      report, we describe a case of LP with keratoconus. As seen in our case, LP and
      its characteristic eyelid margin lesions in keratoconus patients can be
      associated with a contact lens intolerance.

PMID- 23001021
TI  - Neurofibromatosis type 1 (NF1) associated with tumor of the corpus callosum.
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF1), one of the most common
      neurocutaneous disorders, is a multisystemic disease associated with tumors in
      any organ of the body, especially in the central nervous system and also the
      peripheral nervous system. Pilocytic astrocytomas have been described in almost
      all intracranial regions in patients with NF1. However, only a few patients with
      NF1 and tumor of the corpus callosum have been reported to date. MATERIAL AND
      METHODS: An 11-year-old white Spanish boy was evaluated due to a family history
      of NF1 and low performance test scores in school. He was studied from the
      neurological and intellectual level points of view. RESULTS: Magnetic resonance
      (MR) study revealed a tumor in the anterior-middle portion of the corpus callosum
      and a Wechsler Intelligence Scale for Children-Revised showed verbal IQ of 92, a
      performance IQ of 108, and a total IQ of 100. In addition, he showed attention
      deficit and hyperactivity disorder. CONCLUSIONS: Tumors of corpus callosum in
      patients with NF1 are very uncommon. The patient presented in this paper
      consulted due to family history of NF1, progressive hyperactivity, and below
      average school performance. The MR study showed tumor in the corpus callosum.
      Tumor histology was not investigated.

PMID- 23001022
TI  - Neurogenic vasomotor instability and Chiari malformation.

PMID- 23001023
TI  - The role of neuroimaging in the evaluation process of children with isolated
      sixth nerve palsy.
AB  - PURPOSE: The purpose of this study was to assess the role of neuroimaging in
      identifying the etiology of pediatric isolated sixth nerve palsy (SNP). METHODS:
      A retrospective cohort study was conducted of all patients younger than 18 years
      of age with an isolated SNP seen at our medical center between 2003 and 2011.
      RESULTS: Sixteen children (nine girls; mean age, 4.5 years) with isolated SNP
      were identified during an 8-year period. Only cases with normal optic disk
      appearance and otherwise normal neurological examination were included into this
      study. Thus, 12 other children with SNP were excluded: ten children with
      papilledema, one child who developed a SNP following a resection of a brain
      tumor, and one with hydrocephalus and a shunt malfunction. All cases of isolated
      SNP were unilateral (ten left eyes). The most common cause for the SNP in these
      children was a tumor that was found in five patients. Other etiologies
      encountered in decreasing frequencies were: benign recurrent SNP (in four
      children), postviral or vaccination (in three children), and one case each of
      post trauma, Chiari malformation, congenital, and undetermined. Children who were
      found to have a tumor (9.9 +/- 5.5 years) were significantly older (P = 0.019)
      than children who did not have a tumor (2.1 +/- 1.8 years). CONCLUSIONS: Isolated
      SNP can be the presentation of a brain tumor in children, and therefore, early
      neuroimaging of the brain is recommended, especially in older children.

PMID- 23001024
TI  - The challenge of managing hemophilia A and STEC-induced hemolytic uremic
      syndrome.
AB  - BACKGROUND: The hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy
      leading to acute kidney injury in children. In most cases it is triggered by an
      infection caused by Shiga-like toxin-producing Escherichia coli (STEC).
      Endothelial damage plays a central role in the pathogenesis of disease.
      Hemophilia A is a genetic disorder leading to factor VIII (FVIII) deficiency, an
      important factor in the coagulation system. CASE: Here we describe a hemophilia A
      patient who developed HUS due to a STEC O26 infection. The patient developed not
      only acute kidney injury, but also severe gastro-intestinal and neurological
      complications. Increased amounts of recombinant FVIII (rFVIII) had to be
      administered during the acute phase of the disease to reach acceptable blood
      levels of FVIII, in order to control the hemorrhagic colitis and to prevent
      severe neurological complications. CONCLUSION: The patient's treatment schedule
      of rFVIII during the HUS period was a serious challenge, and we cannot exclude
      that it contributed to the severity of the HUS by enhancing the thrombotic
      microangiopathic process. The role of factor VIII administration in the severe
      outcome of this disease is discussed.

PMID- 23001025
TI  - A universal immuno-PCR platform for comparative and ultrasensitive quantification
      of dual affinity-tagged proteins in complex matrices.
AB  - Protein detection in complex biological fluids and matrices has become a widely
      diversified field utilizing a number of different technologies. The
      quantification of target proteins in complex media such as serum remains a
      challenge for most technologies such as mass spectrometry, ELISA and western
      blot. Quantitative Immuno-PCR has been heavily used for antigen detection in
      immunoassays, but minimally so for quantifying affinity-tagged proteins expressed
      or circulating in complex matrices--despite its high sensitivity and robustness-
      because it suffers from detrimental background effects arising from its extreme
      detection power. We report the development of a universal qIPCR-based platform
      for the reproducible detection of dual affinity-tagged protein analytes in crude
      complex matrices such as serum and cell culture media or lysates. The system uses
      a couple of high-affinity antibodies against two affinity tags (GFP and HA) for
      the detection of dual-tagged proteins. The dual-tagged analyte is immuno-captured
      by one of its tags, while the second tag is bound by a detection device
      consisting of a new kind of self-assembled antibody-DNA conjugate. The new qIPCR
      platform enabled picomolar quantification of dual-tagged sortase in crude serum
      in 4 h including the PCR step.

PMID- 23001026
TI  - The 13-valent pneumococcal conjugate vaccine for invasive pneumococcal disease in
      Alaska native children: results of a clinical trial.
AB  - BACKGROUND: During 1996 to 2000, Alaska Native children aged <5 years from Yukon
      Kuskokwim Delta (YKD) had invasive pneumococcal disease (IPD) rates 10-fold
      higher than non-Alaska Native children (547/100,000/yr versus 56/100,000/yr).
      After 7-valent pneumococcal conjugate vaccine (PCV7) introduction, IPD rates
      decreased to 148 per 100,000 during 2001 to 2004, increasing to 426 per 100,000
      during 2005 to 2007 due to non-vaccine serotype disease. In 2009, we evaluated
      safety, immunogenicity and impact of 13-valent PCV (PCV13) in YKD children.
      METHODS: In a prelicensure open-label clinical trial, eligible YKD children aged
      <5 years were offered PCV13 as appropriate for age and prior PCV7 history. PCV13
      impact was assessed using existing Alaska-wide IPD surveillance. Serotype
      specific anti-pneumococcal IgG levels were measured postinfant series and
      posttoddler dose in a subset of subjects. Adverse events and serious adverse
      events were collected in all; local reactions and systemic events were collected
      in toddlers. All YKD children were offered licensed PCV13 when it became
      available. RESULTS: Three hundred seventy-two subjects received PCV13 during the
      clinical trial and 3342 postlicensure (April 2010 to August 2011). Adverse events
      were typically mild, or generally consistent with common childhood illnesses. IgG
      levels following PCV13 were similar to other populations. In YKD children aged <5
      years, 52 IPD cases (31 PCV13-serotype) occurred during 2005 to 2008
      (399.0/100,000/yr) versus 9 (7 PCV13-serotype) during January 2009 to August 2011
      (106.7/100,000/yr; P < 0.001). No PCV13-serotype cases occurred among PCV13
      recipients (3680 person follow-up years). CONCLUSIONS: PCV13-serotype IPD
      incidence declined significantly after PCV13 introduction. Although non-PCV13
      serotype IPD also declined significantly, absence of PCV13-serotype IPD in
      children who received PCV13 suggests a protective vaccine effect.

PMID- 23001027
TI  - Clinical and microbiologic features guiding treatment recommendations for brain
      abscesses in children.
AB  - BACKGROUND: There are no guidelines for the management of brain abscesses in
      children, and there is a paucity of recent data describing clinical and
      microbiologic features. We aimed to identify factors affecting outcome to inform
      antibiotic recommendations. METHODS: From 1999 to 2009, 118 children presented
      with brain abscesses to 4 neurosurgical centers in the United Kingdom. Clinical,
      microbiologic and treatment data were collected. RESULTS: The commonest preceding
      infection was sinusitis, with 59% of all children receiving antibiotics before
      diagnosis. Nonspecific symptoms were common, with only 13% having the triad of
      fever, headache and focal neurological deficit. Time between symptom onset and
      diagnosis varied widely (median, 10 days; range, 0-44). Magnetic resonance
      imaging was more frequently diagnostic than computed tomography. The most
      frequent organisms were Streptococcus milleri (38%), except after penetrating
      head injury or neurosurgery, for which Staphylococcus aureus was most common. The
      commonest empiric antibiotics were ceftriaxone/cefotaxime and metronidazole,
      which offered effective antimicrobial therapy in up to 83% of cases.
      Metronidazole added benefit in a maximum of 7% of cases, with
      ceftriaxone/cefotaxime alone sufficient in at least 76% and in all cases with
      cyanotic congenital heart disease or meningitis. A carbapenem would have been
      effective in 90%. The case fatality rate was 6% (33% in the immunocompromised).
      Long-term neurological sequelae affected 35%. Age younger than 5 years and a
      Glasgow Coma Scale score <=8 were associated with poor outcome at 6 months.
      CONCLUSIONS: We recommend ceftriaxone/cefotaxime and metronidazole as empiric
      treatment, although metronidazole may be unnecessary in many cases, with
      antistaphylococcal cover in cases of head trauma. Meropenem potentially would be
      a better choice in the immunocompromised. A prospective study of intravenous and
      oral treatment guided by clinical improvement is required beause 1-2 weeks of
      intravenous antibiotics during a total of 6 weeks may be sufficient in children.

PMID- 23001028
TI  - Tetanus immunity as a surrogate for past diphtheria-tetanus-pertussis
      immunization in migrant children.
AB  - BACKGROUND: Data on vaccination coverage in recently arrived refugee children are
      essential to formulate catch-up recommendations. "Overimmunizing" is costly and
      associated with risks of hyperimmunization, whereas assuming up-to-date
      immunizations may be misleading. METHODS: We retrospectively collected data from
      92 migrant children referred to our hospital between January 2009 and May 2010.
      RESULTS: According to our guidelines, 68 (73.9%) children without evidence of up
      to-date immunizations received a booster dose of an age-appropriate tetanus
      containing vaccine. As a surrogate for diphtheria-tetanus-pertussis-poliomyelitis
      immunity, tetanus antibodies were measured by enzyme-linked immunosorbent assay 1
      month later in 55 of 68 (80.8%) children 6 months to 16 years of age (median, 7
      years) from 23 countries. All but 2 children (3.6%) had reached high antibody
      titers (>1.0 IU/mL) and required no further booster. Unnecessary additional
      tetanus immunizations thus were avoided in 53 of 55 (96.4%) patients. CONCLUSION:
      Assessing antitetanus antibody responses in migrant children allows individual
      vaccination schedules and avoids the risks of hyperimmunization.

PMID- 23001029
TI  - Time matters: pathological effects of repeated psychosocial stress during the
      active, but not inactive, phase of male mice.
AB  - Recent findings in rats indicated that the physiological consequences of repeated
      restraint stress are dependent on the time of day of stressor exposure. To
      investigate whether this is also true for clinically more relevant psychosocial
      stressors and whether repeated stressor exposure during the light phase or dark
      phase is more detrimental for an organism, we exposed male C57BL/6 mice to social
      defeat (SD) across 19 days either in the light phase between Zeitgeber time (ZT)1
      and ZT3 (SDL mice) or in the dark phase between ZT13 and ZT15 (SDD mice). While
      SDL mice showed a prolonged increase in adrenal weight and an attenuated adrenal
      responsiveness to ACTH in vitro after stressor termination, SDD mice showed
      reduced dark phase home-cage activity on observation days 7, 14, and 20,
      flattening of the diurnal corticosterone rhythm, lack of social preference, and
      higher in vitro IFNgamma secretion from mesenteric lymph node cells on day 20/21.
      Furthermore, the colitis-aggravating effect of SD was more pronounced in SDD than
      SDL mice following dextran sulfate sodium treatment. In conclusion, the present
      findings demonstrate that repeated SD effects on behavior, physiology, and
      immunology strongly depend on the time of day of stressor exposure. Whereas
      physiological parameters were more affected by SD during the light/inactive phase
      of mice, behavioral and immunological parameters were more affected by SD during
      the dark phase. Our results imply that repeated daily SD exposure has a more
      negative outcome when applied during the dark/active phase. By contrast, the
      minor physiological changes seen in SDL mice might represent beneficial
      adaptations preventing the formation of those maladaptive consequences.

PMID- 23001030
TI  - Oxadiazolyl-pyridines and perfluoroalkyl-carboxylic acids as building blocks for
      protic ionic liquids: crossing the thin line between ionic and hydrogen bonded
      materials.
AB  - A series of 18 samples has been prepared in order to obtain fluorinated materials
      as Protic Ionic Liquids (PILs). These were synthesized by appropriately mixing
      1,2,4-oxadiazoles derivatised with two pyridines, or one pyridine and a
      fluorinated chain, and perfluoroalkyl-carboxylic acids, either mono- or
      dicarboxylic, leading to symmetric and non-symmetric materials. Many of them
      showed low melting points. However, the possibility of classifying the
      synthesized materials as PILs is discussed in terms of effective ionicity of the
      systems by the combination of Density Functional Theory (DFT) calculation and IR
      spectroscopy. The important outcome of our investigation is that the complete
      proton transfer reaction cannot be taken for granted. The thermal behaviour of
      the new fluorinated materials was also studied by Differential Scanning
      Calorimetry (DSC) and Thermogravimetric analysis (TGA).

PMID- 23001031
TI  - Template-free approach to synthesize hierarchical porous nickel cobalt oxides for
      supercapacitors.
AB  - Nickel cobalt oxides with various Ni/Co ratios were synthesized using a facile
      template-free approach for electrochemical supercapacitors. The texture and
      morphology of the nanocomposites were characterized by powder X-ray diffraction
      (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM)
      and Brunauer-Emmett-Teller analysis (BET). The results show that a hierarchical
      porous structure assembled from nanoflakes with a thickness of ~10 nm was
      obtained, and the ratio of nickel to cobalt in the nanocomposites was very close
      to the precursors. Cyclic voltammetry (CV) and galvanostatic charge and discharge
      tests were carried out to study the electrochemical performance. Both nickel
      cobalt oxides (Ni-Co-O-1 with Ni : Co = 1, Ni-Co-O-2 with Ni : Co = 2) outperform
      pure NiO and Co(3)O(4). The Ni-Co-O-1 and Ni-Co-O-2 possess high specific
      capacities of 778.2 and 867.3 F g(-1) at 1 A g(-1) and capacitance retentions of
      84.1% and 92.3% at 10 A g(-1), respectively. After full activation, the Ni-Co-O-1
      and Ni-Co-O-2 could achieve a maximum value of 971 and 1550 F g(-1) and remain at
      ~907 and ~1450 F g(-1) at 4 A g(-1), respectively. Also, the nickel cobalt oxides
      show high capacity retention when fast charging.

PMID- 23001032
TI  - The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III)
      displacement.
AB  - A conserved iron-binding site, the ferroxidase center, regulates the vital iron
      storage role of the ubiquitous protein ferritin in iron metabolism. It is
      commonly thought that two Fe(II) simultaneously bind the ferroxidase center and
      that the oxidized Fe(III)-O(H)-Fe(III) product spontaneously enters the cavity of
      ferritin as a unit. In contrast, in some bacterioferritins and in archaeal
      ferritins a persistent di-iron prosthetic group in this center is believed to
      mediate catalysis of core formation. Using a combination of binding experiments
      and isotopically labeled (57)Fe(II), we studied two systems in comparison: the
      ferritin from the hyperthermophilic archaeal anaerobe Pyrococcus furiosus (PfFtn)
      and the eukaryotic human H ferritin (HuHF). The results do not support either of
      the two paradigmatic models; instead they suggest a unifying mechanism in which
      the Fe(III)-O-Fe(III) unit resides in the ferroxidase center until it is
      sequentially displaced by Fe(II).

PMID- 23001033
TI  - Enzyme redesign guided by cancer-derived IDH1 mutations.
AB  - Mutations in an enzyme can result in a neomorphic catalytic activity in cancers.
      We applied cancer-associated mutations from isocitrate dehydrogenases to
      homologous residues in the active sites of homoisocitrate dehydrogenases to
      derive enzymes that catalyze the conversion of 2-oxoadipate to (R)-2
      hydroxyadipate, a critical step for adipic acid production. Thus, we provide a
      prototypic example of how insights from cancer genome sequencing and functional
      studies can aid in enzyme redesign.

PMID- 23001034
TI  - Two interacting proteins are necessary for the editing of the NdhD-1 site in
      Arabidopsis plastids.
AB  - After transcription, mRNA editing in angiosperm chloroplasts and mitochondria
      results in the conversion of cytidine to uridine by deamination. Analysis of
      Arabidopsis thaliana mutants affected in RNA editing have shown that many
      pentatricopeptide repeat proteins (PPRs) are required for specific cytidine
      deamination events. PPR proteins have been shown to be sequence-specific RNA
      binding proteins allowing the recognition of the C to be edited. The C-terminal
      DYW domain present in many editing factors has been proposed to catalyze C
      deamination, as it shows sequence similarities with cytidine deaminases in other
      organisms. However, many editing factors, such as the first to be discovered,
      CHLORORESPIRATORY REDUCTION4 (CRR4), lack this domain, so its importance has been
      unclear. Using a reverse genetic approach, we identified DYW1, an RNA editing
      factor acting specifically on the plastid ndhD-1 editing site recognized by CRR4.
      Unlike other known editing factors, DYW1 contains no identifiable PPR motifs but
      does contain a clear DYW domain. We were able to show interaction between CRR4
      and DYW1 by bimolecular fluorescence complementation and to reconstitute a
      functional chimeric CRR4-DYW1 protein complementing the crr4 dyw1double mutant.
      We propose that CRR4 and DYW1 act together to edit the ndhD-1 site.

PMID- 23001035
TI  - Mutations in the Arabidopsis H3K4me2/3 demethylase JMJ14 suppress
      posttranscriptional gene silencing by decreasing transgene transcription.
AB  - Posttranscriptional gene silencing (PTGS) mediated by sense transgenes (S-PTGS)
      results in RNA degradation and DNA methylation of the transcribed region. Through
      a forward genetic screen, a mutant defective in the Histone3 Lysine4 di/trimethyl
      (H3K4me2/3) demethylase Jumonji-C (JmjC) domain-containing protein14 (JMJ14) was
      identified. This mutant reactivates various transgenes silenced by S-PTGS and
      shows reduced Histone3 Lysine9 Lysine14 acetylation (H3K9K14Ac) levels, reduced
      polymerase II occupancy, reduced transgene transcription, and increased DNA
      methylation in the promoter region, consistent with the hypothesis that high
      levels of transcription are required to trigger S-PTGS. The jmj14 mutation also
      reduces the expression of transgenes that do not trigger S-PTGS. Moreover,
      expression of transgenes that undergo S-PTGS in a wild-type background is reduced
      in jmj14 sgs3 double mutants compared with PTGS-deficient sgs3 mutants,
      indicating that JMJ14 is required for high levels of transcription in a PTGS
      independent manner. Whereas endogenous loci regulated by JMJ14 exhibit increased
      H3K4me2 and H3K4me3 levels in the jmj14 mutant, transgene loci exhibit unchanged
      H3K4me2 and decreased H3K4me3 levels. Because jmj14 mutations impair PTGS of
      transgenes expressed under various plant or viral promoters, we hypothesize that
      JMJ14 demethylation activity is prevented by antagonistic epigenetic marks
      specifically imposed at transgene loci. Removing JMJ14 likely allows other H3K4
      demethylases encoded by the Arabidopsis thaliana genome to act on transgenes and
      reduce transcription levels, thus preventing the triggering of S-PTGS.

PMID- 23001036
TI  - Failure of the tomato trans-acting short interfering RNA program to regulate
      AUXIN RESPONSE FACTOR3 and ARF4 underlies the wiry leaf syndrome.
AB  - Interfering with small RNA production is a common strategy of plant viruses. A
      unique class of small RNAs that require microRNA and short interfering (siRNA)
      biogenesis for their production is termed trans-acting short interfering RNAs (ta
      siRNAs). Tomato (Solanum lycopersicum) wiry mutants represent a class of
      phenotype that mimics viral infection symptoms, including shoestring leaves that
      lack leaf blade expansion. Here, we show that four WIRY genes are involved in
      siRNA biogenesis, and in their corresponding mutants, levels of ta-siRNAs that
      regulate AUXIN RESPONSE FACTOR3 (ARF3) and ARF4 are reduced, while levels of
      their target ARFs are elevated. Reducing activity of both ARF3 and ARF4 can
      rescue the wiry leaf lamina, and increased activity of either can phenocopy wiry
      leaves. Thus, a failure to negatively regulate these ARFs underlies tomato
      shoestring leaves. Overexpression of these ARFs in Arabidopsis thaliana, tobacco
      (Nicotiana tabacum), and potato (Solanum tuberosum) failed to produce wiry
      leaves, suggesting that the dramatic response in tomato is exceptional. As
      negative regulation of orthologs of these ARFs by ta-siRNA is common to land
      plants, we propose that ta-siRNA levels serve as universal sensors for
      interference with small RNA biogenesis, and changes in their levels direct
      species-specific responses.

PMID- 23001038
TI  - Why wiry? Tomato mutants reveal connections among small RNAs, auxin response
      factors, virus infection, and leaf morphology.

PMID- 23001037
TI  - G protein-coupled receptor-type G proteins are required for light-dependent
      seedling growth and fertility in Arabidopsis.
AB  - G protein-coupled receptor-type G proteins (GTGs) are highly conserved membrane
      proteins in plants, animals, and fungi that have eight to nine predicted
      transmembrane domains. They have been classified as G protein-coupled receptor
      type G proteins that function as abscisic acid (ABA) receptors in Arabidopsis
      thaliana. We cloned Arabidopsis GTG1 and GTG2 and isolated new T-DNA insertion
      alleles of GTG1 and GTG2 in both Wassilewskija and Columbia backgrounds. These
      gtg1 gtg2 double mutants show defects in fertility, hypocotyl and root growth,
      and responses to light and sugars. Histological studies of shoot tissue reveal
      cellular distortions that are particularly evident in the epidermal layer. Stable
      expression of GTG1(pro):GTG1-GFP (for green fluorescent protein) in Arabidopsis
      and transient expression in tobacco (Nicotiana tabacum) indicate that GTG1 is
      localized primarily to Golgi bodies and to the endoplasmic reticulum. Microarray
      analysis comparing gene expression profiles in the wild type and double mutant
      revealed differences in expression of genes important for cell wall function,
      hormone response, and amino acid metabolism. The double mutants isolated here
      respond normally to ABA in seed germination assays, root growth inhibition, and
      gene expression analysis. These results are inconsistent with their proposed role
      as ABA receptors but demonstrate that GTGs are fundamentally important for plant
      growth and development.

PMID- 23001039
TI  - Essential role of VIPP1 in chloroplast envelope maintenance in Arabidopsis.
AB  - VESICLE-INDUCING PROTEIN IN PLASTIDS1 (VIPP1), proposed to play a role in
      thylakoid biogenesis, is conserved in photosynthetic organisms and is closely
      related to Phage Shock Protein A (PspA), which is involved in plasma membrane
      integrity in Escherichia coli. This study showed that chloroplasts/plastids in
      Arabidopsis thaliana vipp1 knockdown and knockout mutants exhibit a unique
      morphology, forming balloon-like structures. This altered morphology, as well as
      lethality of vipp1, was complemented by expression of VIPP1 fused to green
      fluorescent protein (VIPP1-GFP). Several lines of evidence show that the balloon
      chloroplasts result from chloroplast swelling related to osmotic stress,
      implicating VIPP1 in the maintenance of plastid envelopes. In support of this,
      Arabidopsis VIPP1 rescued defective proton leakage in an E. coli pspA mutant.
      Microscopy observation of VIPP1-GFP in transgenic Arabidopsis revealed that VIPP1
      forms large macrostructures that are integrated into various morphologies along
      the envelopes. Furthermore, live imaging revealed that VIPP1-GFP is highly mobile
      when chloroplasts are subjected to osmotic stress. VIPP1-GFP showed dynamic
      movement in the transparent area of spherical chloroplasts, as the fluorescent
      molecules formed filament-like structures likely derived from disassembly of the
      large VIPP1 complex. Collectively, our data demonstrate that VIPP1 is a
      multifunctional protein in chloroplasts that is critically important for envelope
      maintenance.

PMID- 23001041
TI  - NEDDylation controls the target specificity of E2F1 and apoptosis induction.
AB  - The transcription factor E2F1 has pivotal roles in both cell proliferation and
      cell death, and is an important molecular target in cancer. Under proliferative
      conditions E2F1 induces the expression of genes that promote cell cycle
      progression, such as E2F2, whereas under proapoptotic conditions E2F1 induces
      expression of genes such as p73 that lead to apoptosis. The mechanism by which
      the apoptotic function of E2F1 is activated remains unclear, however. We now show
      that members of the E2F family are covalently conjugated with the ubiquitin-like
      modifier NEDD8. Overexpression of SENP8, a NEDD8-specific cysteine protease,
      resulted in deNEDDylation of E2F1 and promoted its transactivation activity at
      the p73 gene but not at the E2F2 gene. Knockdown of SENP8, on the other hand,
      attenuated p73 expression and apoptosis induced by E2F1 or by DNA damage. SENP8
      also promoted the interaction between E2F1 and its cofactor Microcephalin 1,
      which is required for p73 induction. These results suggest that NEDDylation is a
      molecular trigger that modifies the target specificity of E2F1, and could have
      important implications for E2F1 regulation of apoptosis.

PMID- 23001040
TI  - The biology and clinical significance of acquired genomic copy number aberrations
      and recurrent gene mutations in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western
      world and remains incurable with conventional chemotherapy treatment approaches.
      CLL as a disease entity is defined by a relatively parsimonious set of diagnostic
      criteria and therefore likely constitutes an umbrella term for multiple related
      illnesses. Of the enduring fundamental biological processes that affect the
      biology and clinical behavior of CLL, few are as central to the pathogenesis of
      CLL as recurrent acquired genomic copy number aberrations (aCNA) and recurrent
      gene mutations. Here, a state-of-the-art overview of the pathological anatomy of
      the CLL genome is presented, including detailed descriptions of the anatomy of
      aCNA and gene mutations. Data from SNP array profiling and large-scale sequencing
      of large CLL cohorts, as well as stimulated karyotyping, are discussed. This
      review is organized by discussions of the anatomy, underlying pathomechanisms and
      clinical significance of individual genomic lesions and recurrent gene mutations.
      Finally, gaps in knowledge regarding the biological and clinical effects of
      recurrent genomic aberrations or gene mutations on CLL are outlined to provide
      critical stimuli for future research.

PMID- 23001043
TI  - MicroRNA-34 suppresses breast cancer invasion and metastasis by directly
      targeting Fra-1.
AB  - MicroRNAs have key roles in tumor metastasis. Here, we describe the regulation
      and function of miR-34a and miR-34c (miR-34a/c) in breast cancer metastasis.
      Expression analysis verified that miR-34a/c expression is significantly decreased
      in metastatic breast cancer cells and human primary breast tumors with lymph node
      metastases. Overexpression of miR-34a/c could inhibit breast cancer cell
      migration and invasion in vitro and distal pulmonary metastasis in vivo. Further
      studies revealed that Fos-related antigen 1 (Fra-1 or Fosl1) is a downstream
      target of miR-34a/c as miR-34a/c bound directly to the 3'untranslated region of
      Fra-1, subsequently reducing both the mRNA and protein levels of Fra-1. Silencing
      of Fra-1 recapitulated the effects of miR-34a/c overexpression, whereas enforced
      expression of Fra-1 reverses the suppressive effects of miR-34a/c. Moreover,
      significant downregulation of miR-34a in metastatic breast cancer tissues was
      found to be inversely correlated with Fra-1 expression. Our results demonstrate
      that miR-34a/c functions as a metastasis suppressor to regulate breast cancer
      migration and invasion through targeting Fra-1 oncogene and suggest a therapeutic
      application of miR-34 in breast cancer.

PMID- 23001044
TI  - High citrulline-to-arginine ratio associated with blood pressure abnormalities in
      children with early chronic kidney disease.
AB  - BACKGROUND: Nitric oxide (NO) is involved in hypertension and chronic kidney
      disease (CKD). NO synthase can metabolize L-arginine (ARG) to generate NO and L
      citrulline (CIT). Two methylated ARG derivatives, asymmetric and symmetric
      dimethylarginine, are also involved in NO deficiency. Thus it was hypothesized
      that their combined ratios relate to blood pressure (BP) abnormalities in
      children with early CKD. METHODS AND RESULTS: The relationship between these ARG
      metabolites in plasma was examined using 24-h ambulatory BP monitoring (ABPM)
      profile in children and adolescents with CKD stages 1-3 (n=44). Approximately
      20.4% (9/44) of children with CKD stages 1-3 were diagnosed with hypertension on
      clinical BP measurement, and 77.3% (33/44) had BP abnormalities on ABPM,
      including increased BP load, nocturnal BP non-dipping, and nocturnal
      hypertension. Children with CKD stages 2-3 were more prevalent with abnormal BP
      on ABPM, and had a higher level of CIT and CIT-to-ARG ratio than those with stage
      1. Furthermore, high CIT-to-ARG ratio was significantly correlated with abnormal
      ABPM profile, including nocturnal hypertension, increased diastolic BP load, and
      nocturnal BP non-dipping. Higher CIT level was significantly correlated with
      increased diastolic BP load and overall ABPM profile. CONCLUSIONS: Plasma CIT-to
      ARG ratio may serve as a useful marker of cardiovascular outcome in children with
      early CKD.

PMID- 23001042
TI  - Neurotrophin-3 modulates breast cancer cells and the microenvironment to promote
      the growth of breast cancer brain metastasis.
AB  - Metastasis, which remains incompletely characterized at the molecular and
      biochemical levels, is a highly specific process. Despite the ability of
      disseminated cancer cells to intravasate into distant tissues, it has been long
      recognized that only a limited subset of target organs develop clinically overt
      metastases. Therefore, subsequent adaptation of disseminated cancer cells to
      foreign tissue microenvironment determines the metastatic latency and tissue
      tropism of these cells. As a result, studying interactions between the
      disseminated cancer cells and the adjacent stromal cells will provide a better
      understanding of what constitutes a favorable or unfavorable microenvironment for
      disseminated cancer cells in a tissue-specific manner. Previously, we reported a
      protein signature of brain metastasis showing increased ability of brain
      metastatic breast cancer cells to counteract oxidative stress. In this study, we
      showed that another protein from the brain metastatic protein signature,
      neurotrophin-3 (NT-3), has a dual function of regulating the metastatic growth of
      metastatic breast cancer cells and reducing the activation of immune response in
      the brain. More importantly, increased NT-3 secretion in metastatic breast cancer
      cells results in a reversion of mesenchymal-like (EMT) state to epithelial-like
      (MET) state and vice versa. Ectopic expression of NT-3 in EMT-like breast cancer
      cells reduces their migratory ability and increases the expression of HER2 (human
      epidermal growth factor receptor 2) and E-cadherin at the cell-cell junction. In
      addition, both endogenous and ectopic expression of NT-3 reduced the number of
      fully activated cytotoxic microglia. In summary, NT-3 appears to promote growth
      of metastatic breast cancer cells in the brain by facilitating the re
      epithelialization of metastatic breast cancer cells and downmodulating the
      cytotoxic response of microglia. Most importantly, our results provide new
      insights into the latency and development of central nervous system
      macrometastases in patients with HER2-positive breast tumors and provide
      mechanistic rationale to target HER2 signaling for HER2-positive breast cancer
      brain metastasis.

PMID- 23001045
TI  - In vivo cardiac diffusion-weighted magnetic resonance imaging: quantification of
      normal perfusion and diffusion coefficients with intravoxel incoherent motion
      imaging.
AB  - OBJECTIVES: Diffusion-weighted imaging (DWI) and the introduction of the
      intravoxel incoherent motion (IVIM) model have provided a unique method for
      evaluating perfusion and diffusion within a tissue without the need for a
      contrast agent. Despite its relevance, cardiac DWI has thus far been limited by
      low b values because of signal loss induced by physiological motion. The goal of
      this study was to develop a methodology for estimating IVIM parameters of in vivo
      cardiac magnetic resonance imaging using an efficient DWI acquisition framework.
      This was achieved by investigating various acquisition strategies (principal
      component analysis [PCA] filtering and temporal maximum intensity projection
      [PCATMIP] and single trigger delay [TD]) and fitting methods. MATERIAL AND
      METHODS: Simulations were performed on a synthetic dataset of diffusion-weighted
      signal intensity (SI) to determine the fitting method that would yield IVIM
      parameters with the greatest accuracy. The required number of b values to
      correctly estimate IVIM parameters was also investigated. Breath-hold DWI scans
      were performed for 12 volunteers to collect several TD values during diastole.
      Thirteen b values ranging from 0 to 550 s/mm were used. The IVIM parameters
      derived using the data from all the acquired TDs (PCATMIP technique) were
      compared with those derived using a single acquisition performed at an optimized
      diastolic time point (1TD). RESULTS: The main result of this study was that
      PCATMIP, when combined with a fitting model that accounted for T1 and T2
      relaxation, provided IVIM parameters with less variability. However, an
      acquisition performed with 1 optimized diastolic TD provided results that were as
      good as those provided using PCATMIP if the R-R variability during the
      acquisition was sufficiently low (+/- 5%). Furthermore, the use of only 9 b
      values (that could be acquired in 2 breath-holds), instead of 13 b values
      (requiring 3 breath-holds), was sufficient to determine the IVIM parameters.
      CONCLUSIONS: This study demonstrates that IVIM is technically feasible in vivo
      and reports for the first time the perfusion fraction, f, and the diffusion
      coefficients, D and D*, for the cardiac DWI of healthy volunteers. Motion-induced
      signal loss, which is the main problem associated with cardiac DWI, could be
      avoided with the combined use of sliding acquisition during the cardiac cycle and
      image postprocessing with the PCATMIP algorithm. This study provides new
      perspectives for perfusion imaging without a contrast agent and demonstrates that
      IVIM parameters can act as promising tools to further characterize microvascular
      abnormalities or dysfunction.

PMID- 23001046
TI  - Surgical management of pelvic organ prolapse and uterine descent in the
      Netherlands.
AB  - INTRODUCTION AND HYPOTHESIS: To evaluate current practice in the surgical
      treatment of uterine descent among members of the Dutch Urogynecological Society
      and to analyze possible trends in the surgical treatment of pelvic organ prolapse
      in the Netherlands during the last decade. METHODS: A questionnaire, including
      case scenarios, was sent to the members of the Dutch Urogynecological Society.
      Using a nationwide registry from the Netherlands, we assessed the number and type
      of surgical procedures performed for pelvic organ prolapse between 1997 and 2009.
      RESULTS: The response rate was 73%, with 161 questionnaires completed. Vaginal
      hysterectomy, sacrospinous hysteropexy, and the Manchester Fothergill procedure
      were the most frequently performed surgical interventions for uterine descent. In
      the case of lower stage uterine descent, uterus preservation was preferred, but
      in the case of higher stage there was wide variation. Two thirds of the
      respondents stated that in recent years they tended to save the uterus more
      often. The registered number of hospital admissions for uterine descent increased
      by 30% between 1997 and 2009 and the number of surgical procedures almost
      doubled. The number of vaginal hysterectomies performed because of uterine
      descent increased by only 15% in this period. CONCLUSIONS: In the Netherlands,
      surgical policy in the case of uterine descent is very variable, with no clear
      preference for either hysterectomy or uterus preservation. There was a high
      increase in hospital admissions and pelvic organ prolapse procedures in the last
      decade. The number of vaginal hysterectomies performed because of uterine descent
      did not follow this change, which reflects a trend toward preserving the uterus.

PMID- 23001047
TI  - Pelvic organ support, symptoms and quality of life during pregnancy: a
      prospective study.
AB  - INTRODUCTION AND HYPOTHESIS: Prevalence studies show an increase in lower urinary
      tract and pelvic floor symptoms during pregnancy. The aim of our prospective
      study was to evaluate changes in pelvic organ support, pelvic floor symptoms and
      their effect on quality of life (QOL) during the first pregnancy using validated
      measures. We hypothesised that pregnancy is associated with worsening of pelvic
      floor function. METHODS: Objective assessment of pelvic organ support using the
      Pelvic Organ Prolapse Quantification (POP-Q) system and subjective evaluation of
      symptoms of pelvic floor disorders and related QOL with the electronic Personal
      Assessment Questionnaire-Pelvic Floor (ePAQ-PF) were performed in the second
      trimester and then repeated at 36 weeks gestation. RESULTS: A total of 182
      nulliparae attended the first visit at 20 weeks and 150 (82.4%) women returned
      for follow-up at 36 weeks gestation. There were no significant changes in POP-Q
      points or stage between the two visits except for a significant increase in
      genital hiatus (p = 0.0001) and perineal body length (p = 0.0001). The vaginal
      symptoms did not show any changes. Symptoms and bother with voiding difficulties
      and stress urinary incontinence increased during pregnancy. Constipation (p =
      0.02) and evacuation subdomains improved significantly (p = 0.009). In the sexual
      domain, the only subdomain that worsened significantly (p = 0.03) was "sex and
      vaginal symptoms". None of the pelvic floor symptoms impacted the QOL.
      CONCLUSIONS: In our group of nulliparae, pelvic floor-related QOL and prolapse
      stage did not change significantly from the second to the third trimester of
      pregnancy.

PMID- 23001048
TI  - Treatment of cystinosis with delayed-release cysteamine: 6-year follow-up.
AB  - BACKGROUND: Patients with nephropathic cystinosis are required to take 6-hourly
      immediate-release cysteamine (Cystagon(r)) to reduce disease progression. This
      arduous regimen affects quality of life, disrupts sleep, and may result in non
      compliance with therapy. Enteric-coated cysteamine bitartrate (EC-cysteamine) was
      developed as a "proof-of-concept" formulation for twice-daily ingestion. Previous
      reports have shown this therapy to be effective up to a mean of 14 months. CASE
      DIAGNOSIS/TREATMENT: Two subjects (aged 13 and 15 years) received EC-cysteamine
      for 5-6 years at 60-65 % of their previous total daily dose of immediate-release
      cysteamine given at 6-h intervals. White blood cell (WBC) cystine levels were
      monitored every 1-3 months. CONCLUSION: The administration of EC-cysteamine did
      not result in any change in mean trough WBC cystine levels or any deterioration
      in the estimated glomerular filtration rate, thyroid, or liver function,
      suggesting that delayed-release, twice-daily EC-cysteamine is an effective long
      term treatment alternative to immediate-release cysteamine given at 6-h
      intervals.

PMID- 23001049
TI  - Lanthanide-doped upconverting phosphors for bioassay and therapy.
AB  - Lanthanide-doped fluorescent materials have gained increasing attention in recent
      years due to their unique luminescence properties which have led to their use in
      wide-ranging fields including those of biological applications. Aside from being
      used as agents for in vivo imaging, lanthanide-doped fluorescent materials also
      present many advantages for use in bioassays and therapy. In this review, we
      summarize the applications of lanthanide-doped up-converting phosphors (UCPs) in
      protein and gene detection, as well as in photodynamic and gene therapy in recent
      years, and outline their future potential in biological applications. The current
      report could serve as a reference for researchers in relevant fields.

PMID- 23001050
TI  - Reoperations for primary hyperparathyroidism--improvement of outcome over two
      decades.
AB  - PURPOSE: Reoperations (R-PTX) for primary hyperparathyroidism (pHPT) are
      challenging, since they are associated with increased failure and morbidity
      rates. The aim was to evaluate the results of reoperations over two decades, the
      latter considering the implementation of Tc(99m)sestamibi-SPECT (Mibi/SPECT),
      intraoperative parathormone (IOPTH) measurement, and intraoperative
      neuromonitoring (IONM). PATIENTS AND METHODS: Data of 1,363 patients who
      underwent surgery for pHPT were retrospectively analyzed regarding reoperations.
      Causes of persistent (p) pHPT or recurrent (r) pHPT, preoperative imaging
      studies, surgical findings, and outcome were analyzed. Data of patients who
      underwent surgery between 1987 and 1997 (group 1; G1) and between 1998 and 2008
      (group 2; G2) with the use of Mibi/SPECT, IOPTH, and IONM were evaluated.
      RESULTS: One hundred twenty-five patients with benign ppHPT (n = 108) or rpHPT (n
      = 17) underwent reoperations (R-PTX). Group 1 included 54, group 2 71 patients.
      Main cause of ppHPT (G1 = 65 % vs. G2 = 53 %) and rpHPT (G1 = 80 % vs. G2 = 60 %)
      was the failed detection of a solitary adenoma (p = 0.2). Group 1 patients had
      significantly less unilateral/focused neck re-explorations (G1 = 23 % vs. G2 = 57
      %, p = 0.0001), and more sternotomies (G1 = 35 vs. G2 = 14 %, p = 0.01). After a
      median follow-up of 4 (range 0.9-23.4) years, reversal of hypercalcemia was
      achieved in 91 % (G1) and in 98.6 % in group 2 (p = 0.08, OR 7.14 [0.809-63.1]).
      The rates of permanent recurrent laryngeal nerve palsy (G1 = G2 = 9 %, p = 1) and
      of postoperative permanent hypoparathyroidism (G1 = 9 % vs. G2 = 6 %, p = 0.5)
      were not significantly different. Other complications such as wound infection,
      postoperative bleeding, and pneumonia were significantly lower in group 2 (p <
      0.001). CONCLUSION: Nowadays, cure rates of R-PTX are nearly the same as in
      primary operations for pHPT. These results can be achieved in high-volume centers
      by routine use of well-established preoperative Mibi/SPECT and US in combination
      with IOPTH. However, morbidity is still considerably high.

PMID- 23001051
TI  - Synthesis, characterization, and antibacterial and anticancer screening of {M(2+)
      Co (3+)-M (2+)} and {Co (3+)-M (2+)} (M is Zn, Cd, Hg) heterometallic complexes.
AB  - The cobalt(III) complexes Et(4)N[Co(L(1))(2)] and [Co(L(2))(3)] [H(2)L(1) is 2,6
      bis(N-(2-pyridyl)carbamoyl)pyridine and HL(2) is 2-(N-(2
      pyridyl)carbamoyl)pyridine] were used as the building blocks for preparing a
      series of {M(2+)-Co(3+)-M(2+)} (where M is Zn, Cd, or Hg) and {Co(3+)-M(2+)}
      (where M is Zn or Cd) heterometallic complexes. All heterometallic complexes were
      characterized using a host of spectroscopic methods (IR, NMR, and UV/vis
      spectroscopy and mass spectrometry), elemental analysis, and conductivity
      measurements. One of the representative compounds, {Hg(2+)-Co(3+)-Hg(2+)}, was
      characterized crystallographically, and it was revealed that two Hg(II) ions are
      coordinated within the clefts created by the building block Et(4)N[Co(L(1))(2)].
      The results of screening for anticancer activity against the human brain tumor
      U87 cell line and antibacterial activity against a range of resistant
      (Pseudomonas aeruginosa and Proteus vulgaris) as well as standard (Staphylococcus
      aureus SA 96, P. aeruginosa MTCC 1688, Klebsiella planticola MTCC 2272, and
      Escherichia coli T7) bacterial strains indicate promising activities. Notably,
      the observed activity was found to vary with the type of building block and the
      secondary metal ion present in the heterometallic complex. Treatment-induced cell
      death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT and
      macrocolony assay), growth inhibition, cytogenetic damage, cell cycle delay, and
      apoptosis were studied as the parameters for cellular response.

PMID- 23001052
TI  - Propofol at clinically relevant concentrations increases neuronal differentiation
      but is not toxic to hippocampal neural precursor cells in vitro.
AB  - BACKGROUND: Propofol in the early postnatal period has been shown to cause brain
      cell death. One proposed mechanism for cognitive dysfunction after anesthesia is
      alteration of neural stem cell function and neurogenesis. We examined the effect
      of propofol on neural precursor or stem cells (NPCs) grown in vitro. METHODS:
      Hippocampal-derived NPCs from postnatal day 2 rats were exposed to propofol or
      Diprivan. NPCs were then analyzed for bromodeoxyuridine incorporation to measure
      proliferation. Cell death was measured by lactate dehydrogenase release.
      Immunocytochemistry was used to evaluate the expression of neuronal and glial
      markers in differentiating NPCs exposed to propofol. RESULTS: Propofol dose
      dependently increases the release of lactate dehydrogenase from NPCs under both
      proliferating and differentiating conditions at supraclinical concentrations
      (more than 7.1 uM). Both Diprivan and propofol had the same effect on NPCs.
      Propofol-mediated release of lactate dehydrogenase is not inhibited by blocking
      the gamma-aminobutyric acid type A receptor or extracellular calcium influx and
      is not mediated by caspase-3/7. Direct gamma-aminobutyric acid type A receptor
      activation did not have the same effect. In differentiating NPCs, 6 h of propofol
      at 2.1 uM increased the number neurons but not glial cells 4 days later.
      Increased neuronal differentiation was not blocked by bicuculline. CONCLUSIONS:
      Only supraclinical concentrations of propofol or Diprivan kill NPCs in culture by
      a non-gamma-aminobutyric acid type A, noncaspase-3 mechanism. Clinically relevant
      doses of propofol increase neuronal fate choice by a non-gamma-aminobutyric acid
      type A mechanism.

PMID- 23001053
TI  - Intraoperative neuromuscular monitoring site and residual paralysis.
AB  - BACKGROUND: Residual paralysis is common after general anesthesia involving
      administration of neuromuscular blocking drugs (NMBDs). Management of NMBDs and
      reversal is frequently guided by train-of-four (TOF) monitoring. We hypothesized
      that monitoring of eye muscles is associated with more frequent residual
      paralysis than monitoring at the adductor pollicis. METHODS: This prospective
      cohort study enrolled 180 patients scheduled for elective surgery with
      anticipated use of NMBDs. Collected variables included monitoring site, age,
      gender, weight, body mass index, American Society of Anesthesiologists physical
      status class, type and duration of surgery, type of NMBDs, last and total dose
      administered, TOF count at time of reversal, dose of neostigmine, and time
      interval between last dose of NMBDs to quantitative measurement. Upon
      postanesthesia care unit admission, we measured TOF ratios by acceleromyography
      at the adductor pollicis. Residual paralysis was defined as a TOF ratio less than
      90%. Multivariable logistic regression was used to account for unbalances between
      the two groups and to adjust for covariates. RESULTS: 150 patients received NMBDs
      and were included in the analysis. Patients with intraoperative TOF monitoring of
      eye muscles had significantly greater incidence of residual paralysis than
      patients monitored at the adductor pollicis (P < 0.01). Residual paralysis was
      observed in 51/99 (52%) and 11/51 (22%) of patients, respectively. The crude odds
      ratio was 3.9 (95% CI: 1.8-8.4), and the adjusted odds ratio was 5.5 (95% CI: 2.1
      14.5). CONCLUSIONS: Patients having qualitative TOF monitoring of eye muscles had
      a greater than 5-fold higher risk of postoperative residual paralysis than those
      monitored at the adductor pollicis.

PMID- 23001054
TI  - Automatic extraction and processing of small RNAs on a multi-well/multi-channel
      (M&M) chip.
AB  - The study of the regulatory roles in small RNAs can be accelerated by techniques
      that permit simple, low-cost, and rapid extraction of small RNAs from a small
      number of cells. In order to ensure highly specific and sensitive detection, the
      extracted RNAs should be free of the background nucleic acids and present stably
      in a small volume. To meet these criteria, we designed a multi-well/multi-channel
      (M&M) chip to carry out automatic and selective isolation of small RNAs via solid
      phase extraction (SPE), followed by reverse-transcription (RT) to convert them to
      the more stable cDNAs in a final volume of 2 MUL. Droplets containing buffers for
      RNA binding, washing, and elution were trapped in microwells, which were
      connected by one channel, and suspended in mineral oil. The silica magnetic
      particles (SMPs) for SPE were moved along the channel from well to well, i.e. in
      between droplets, by a fixed magnet and a translation stage, allowing the nucleic
      acid fragments to bind to the SMPs, be washed, and then be eluted for RT reaction
      within 15 minutes. RNAs shorter than 63 nt were selectively enriched from cell
      lysates, with recovery comparable to that of a commercial kit. Physical
      separation of the droplets on our M&M chip allowed the usage of multiple channels
      for parallel processing of multiple samples. It also permitted smooth integration
      with on-chip RT-PCR, which simultaneously detected the target microRNA, mir-191,
      expressed in fewer than 10 cancer cells. Our results have demonstrated that the
      M&M chip device is a valuable and cost-saving platform for studying small RNA
      expression patterns in a limited number of cells with reasonable sample
      throughput.

PMID- 23001055
TI  - Photosynthetic efficiency and oxygen evolution of Chlamydomonas reinhardtii under
      continuous and flashing light.
AB  - As a result of mixing and light attenuation in a photobioreactor (PBR),
      microalgae experience light/dark (L/D) cycles that can enhance PBR efficiency.
      One parameter which characterizes L/D cycles is the duty cycle; it determines the
      time fraction algae spend in the light. The objective of this study was to
      determine the influence of different duty cycles on oxygen yield on absorbed
      light energy and photosynthetic oxygen evolution. Net oxygen evolution of
      Chlamydomonas reinhardtii was measured for four duty cycles (0.05, 0.1, 0.2, and
      0.5) in a biological oxygen monitor (BOM). Oversaturating light flashes were
      applied in a square-wave fashion with four flash frequencies (5, 10, 50, and 100
      Hz). Algae were precultivated in a turbidostat and acclimated to a low photon
      flux density (PFD). A photosynthesis-irradiance (PI) curve was measured under
      continuous illumination and used to calculate the net oxygen yield, which was
      maximal between a PFD of 100 and 200 MUmol m-2 s-1. Net oxygen yield under
      flashing light was duty cycle-dependent: the highest yield was observed at a duty
      cycle of 0.1 (i.e., time-averaged PFD of 115 MUmol m-2 s-1). At lower duty
      cycles, maintenance respiration reduced net oxygen yield. At higher duty cycles,
      photon absorption rate exceeded the maximal photon utilization rate, and, as a
      result, surplus light energy was dissipated which led to a reduction in net
      oxygen yield. This behavior was identical with the observation under continuous
      light. Based on these data, the optimal balance between oxygen yield and
      production rate can be determined to maximize PBR productivity.

PMID- 23001056
TI  - An extremely thermostable amylopullulanase from Staphylothermus marinus displays
      both pullulan- and cyclodextrin-degrading activities.
AB  - A gene encoding an amylopullulanase of the glycosyl hydrolase (GH) family 57 from
      Staphylothermus marinus (SMApu) was heterologously expressed in Escherichia coli.
      SMApu consisted of 639 amino acids with a molecular mass of 75.3 kDa. It only
      showed maximal amino acid identity of 17.1 % with that of Pyrococcus furiosus
      amylopullulanase in all identified amylases. Not like previously reported
      amylopullulanases, SMApu has no signal peptide but contains a continuous
      GH57N_Apu domain. It had the highest catalytic efficiency toward pullulan (k
      cat/K m , 342.34 s(-1) mL mg(-1)) and was extremely thermostable with maximal
      pullulan-degrading activity (42.1 U/mg) at 105  degrees C and pH 5.0 and a half
      life of 50 min at 100  degrees C. Its activity increased to 116 % in the presence
      of 5 mM CaCl2. SMApu could also degrade cyclodextrins, which are resistant to the
      other amylopullulanases. The initial hydrolytic products from pullulan, gamma-CD,
      and 6-O-maltooligosyl-beta-CD were [6)-alpha-D-Glcp-(1 -> 4)-alpha-D-Glcp-(1 ->
      4)-alpha-D-Glcp-(1->]n, maltooctaose, and single maltooligosaccharide plus beta
      CD, respectively. The final hydrolytic products from above-mentioned substrates
      were maltose and glucose. These results confirm that SMApu is a novel
      amylopullulanase of the family GH57 possessing the cyclodextrin-degrading
      activity of cyclomaltodextrinase.

PMID- 23001057
TI  - Improving the safety of viral DNA vaccines: development of vectors containing
      both 5' and 3' homologous regulatory sequences from non-viral origin.
AB  - Although some DNA vaccines have proved to be very efficient in field trials,
      their authorisation still remains limited to a few countries. This is in part due
      to safety issues because most of them contain viral regulatory sequences to
      driving the expression of the encoded antigen. This is the case of the only DNA
      vaccine against a fish rhabdovirus (a negative ssRNA virus), authorised in
      Canada, despite the important economic losses that these viruses cause to
      aquaculture all over the world. In an attempt to solve this problem and using as
      a model a non-authorised, but efficient DNA vaccine against the fish rhabdovirus,
      viral haemorrhagic septicaemia virus (VHSV), we developed a plasmid construction
      containing regulatory sequences exclusively from fish origin. The result was an
      "all-fish vector", named pJAC-G, containing 5' and 3' regulatory sequences of
      beta-acting genes from carp and zebrafish, respectively. In vitro and in vivo,
      pJAC-G drove a successful expression of the VHSV glycoprotein G (G), the only
      antigen of the virus conferring in vivo protection. Furthermore, and by means of
      in vitro fusion assays, it was confirmed that G protein expressed from pJAC-G was
      fully functional. Altogether, these results suggest that DNA vaccines containing
      host-homologous gene regulatory sequences might be useful for developing safer
      DNA vaccines, while they also might be useful for basic studies.

PMID- 23001058
TI  - The immunomodulatory effects of lactic acid bacteria for improving immune
      functions and benefits.
AB  - Probiotics have a number of beneficial health effects in humans and animals, such
      as reducing lactose intolerance symptoms and enhancing the bioavailability of
      nutrients. Probiotics help regulate intestinal microflora and immunomodulatory
      properties. Probiotics also decrease the prevalence of allergies in susceptible
      individuals, inhibit the inflammatory responses in the gut, and have antagonistic
      effects against intestinal and food-borne pathogens. Bacteria typically colonize
      the intestinal tract first and then reinforce the host defense systems by
      inducing generalized mucosal immune responses, including modulation of DC/NK
      interaction, a balanced T-helper cell response, self-limited inflammatory
      response, and the secretion of polymeric IgA. A lot of reports showed that lactic
      acid bacteria (LAB) as Lactobacillus and Bifidobacterium and their fermented
      products are effective at enhancing innate and adaptive immunity, prevent gastric
      mucosal lesion development, alleviate allergies, and put up defense against
      intestinal pathogen infection. In this review paper, we compared the influence of
      immunomodulatory effects on the function and efficacy of lactobacillus products
      with different strains. We also discuss the beneficial effects of several LAB
      strain and its derivative products for human immunity and related diseases.

PMID- 23001059
TI  - The dark side of gloss.
AB  - Our visual system relies on the image structure generated by the interaction of
      light with objects to infer their material properties. One widely studied surface
      property is gloss, which can provide information that an object is smooth, shiny
      or wet. Studies have historically focused on the role of specular highlights in
      modulating perceived gloss. Here we show in human observers that glossy surfaces
      can generate both bright specular highlights and dark specular 'lowlights', and
      that the presence of either is sufficient to generate compelling percepts of
      gloss. We show that perceived gloss declines when the image structure generated
      by specular lowlights is blurred or misaligned with surrounding surface shading
      and that perceived gloss can arise from the presence of lowlights in surface
      regions isolated from highlights. These results suggest that the image structure
      generated by specular highlights and lowlights is used to construct our
      experience of surface gloss.

PMID- 23001060
TI  - The spatial structure of a nonlinear receptive field.
AB  - Understanding a sensory system implies the ability to predict responses to a
      variety of inputs from a common model. In the retina, this includes predicting
      how the integration of signals across visual space shapes the outputs of retinal
      ganglion cells. Existing models of this process generalize poorly to predict
      responses to new stimuli. This failure arises in part from properties of the
      ganglion cell response that are not well captured by standard receptive-field
      mapping techniques: nonlinear spatial integration and fine-scale heterogeneities
      in spatial sampling. Here we characterize a ganglion cell's spatial receptive
      field using a mechanistic model based on measurements of the physiological
      properties and connectivity of only the primary excitatory circuitry of the
      retina. The resulting simplified circuit model successfully predicts ganglion
      cell responses to a variety of spatial patterns and thus provides a direct
      correspondence between circuit connectivity and retinal output.

PMID- 23001063
TI  - Late acquired stent malapposition: why, when and how to handle?

PMID- 23001061
TI  - Goal-oriented searching mediated by ventral hippocampus early in trial-and-error
      learning.
AB  - Most behavioral learning in biology is trial and error, but how these learning
      processes are influenced by individual brain systems is poorly understood. Here
      we show that ventral-to-dorsal hippocampal subdivisions have specific and
      sequential functions in trial-and-error maze navigation, with ventral hippocampus
      (vH) mediating early task-specific goal-oriented searching. Although performance
      and strategy deployment progressed continuously at the population level,
      individual mice showed discrete learning phases, each characterized by particular
      search habits. Transitions in learning phases reflected feedforward inhibitory
      connectivity (FFI) growth occurring sequentially in ventral, then intermediate,
      then dorsal hippocampal subdivisions. FFI growth at vH occurred abruptly upon
      behavioral learning of goal-task relationships. vH lesions or the absence of vH
      FFI growth delayed early learning and disrupted performance consistency.
      Intermediate hippocampus lesions impaired intermediate place learning, whereas
      dorsal hippocampus lesions specifically disrupted late spatial learning. Trial
      and-error navigational learning processes in naive mice thus involve a stereotype
      sequence of increasingly precise subtasks learned through distinct hippocampal
      subdivisions. Because of its unique connectivity, vH may relate specific goals to
      internal states in learning under healthy and pathological conditions.

PMID- 23001062
TI  - Slow dynamics and high variability in balanced cortical networks with clustered
      connections.
AB  - Anatomical studies demonstrate that excitatory connections in cortex are not
      uniformly distributed across a network but instead exhibit clustering into groups
      of highly connected neurons. The implications of clustering for cortical activity
      are unclear. We studied the effect of clustered excitatory connections on the
      dynamics of neuronal networks that exhibited high spike time variability owing to
      a balance between excitation and inhibition. Even modest clustering substantially
      changed the behavior of these networks, introducing slow dynamics during which
      clusters of neurons transiently increased or decreased their firing rate.
      Consequently, neurons exhibited both fast spiking variability and slow firing
      rate fluctuations. A simplified model shows how stimuli bias networks toward
      particular activity states, thereby reducing firing rate variability as observed
      experimentally in many cortical areas. Our model thus relates cortical
      architecture to the reported variability in spontaneous and evoked spiking
      activity.

PMID- 23001064
TI  - High efficiency dye-sensitized solar cells exploiting sponge-like ZnO
      nanostructures.
AB  - Sponge-like nanostructured ZnO layers were successfully employed as photoanodes
      for the fabrication of highly efficient dye-sensitized solar cells. The sponge
      like ZnO layers were obtained by room temperature radio-frequency magnetron
      sputtering deposition of metallic zinc, followed by thermal oxidation treatment
      in an ambient atmosphere. The porous films show a 3D branched nanomorphology,
      with a feature similar to natural coral. The morphological and optical properties
      of these layers were studied through field emission scanning electron microscopy,
      specific surface area measurements, ultraviolet-visible transmittance and
      absorption spectroscopy. The sponge-like ZnO film presents a high density of
      branches, with a relatively high specific surface area value, and fine optical
      transmittance. The morphology of the porous structure provides a high number of
      adsorption sites for the anchoring of sensitizer molecules, making it suitable
      for the fabrication of ZnO-based photoanodes for dye-sensitized solar cells. The
      light harvesting performance of the sensitized semiconductor was evaluated by
      current density vs. voltage measurements, incident photon-to-electron conversion
      efficiency, open circuit voltage decay and impedance spectroscopy. The modelling
      of the electrical characteristics evidences a higher electron lifetime and a
      longer charge diffusion length, if compared to standard TiO(2) nanoparticle based
      photoanodes. For ZnO films with a thickness up to 18 MUm, a photoconversion
      efficiency as high as 6.67% and a maximum value of the incident photon-to
      electron collection efficiency equal to 87% at 530 nm were demonstrated.

PMID- 23001065
TI  - Aggregate-data estimation of an individual patient data linear random effects
      meta-analysis with a patient covariate-treatment interaction term.
AB  - Individual patient-data meta-analysis of randomized controlled trials is the gold
      standard for investigating how patient factors modify the effectiveness of
      treatment. Because participant data from primary studies might not be available,
      reliable alternatives using published data are needed. In this paper, I show that
      the maximum likelihood estimates of a participant-level linear random effects
      meta-analysis with a patient covariate-treatment interaction can be determined
      exactly from aggregate data when the model's variance components are known. I
      provide an equivalent aggregate-data EM algorithm and supporting software with
      the R package ipdmeta for the estimation of the "interaction meta-analysis" when
      the variance components are unknown. The properties of the methodology are
      assessed with simulation studies. The usefulness of the methods is illustrated
      with analyses of the effect modification of cholesterol and age on pravastatin in
      the multicenter placebo-controlled regression growth evaluation statin study.
      When a participant-level meta-analysis cannot be performed, aggregate-data
      interaction meta-analysis is a useful alternative for exploring individual-level
      sources of treatment effect heterogeneity.

PMID- 23001066
TI  - Smoking cessation in women at the time of an invasive cardiovascular procedure
      and 3 months later.
AB  - BACKGROUND: Female smokers with coronary heart disease (CHD) are at an increased
      risk for negative health effects. The time of invasive cardiovascular (CV)
      interventions is a critical opportunity to make lifestyle changes to reduce
      future CV interventions. OBJECTIVE: The purpose of this study guided by the
      Health Belief Model was to determine which factors predict smoking cessation (SC)
      in women after an invasive CV procedure. METHODS: A correlational, prospective
      design was used. Data were collected from female smokers at the time of an
      invasive CV intervention (baseline) and 3 months later. Instruments measured
      commitment to stop smoking, perceived threat of CHD and future interventions,
      cessation self-efficacy, barriers to SC, benefits of SC, cues to action, and
      motivation. Analyses included chi2 and t tests and multiple, hierarchical, and
      logistic regression. RESULTS: On average, women (N = 76) were middle aged (mean
      [SD] age, 55.9 [8.0] years), smoked 15.3 (9.8) cigarettes per day, and on average
      smoked for 33.6 (10.2) years. At baseline, fewer perceived barriers to SC, high
      cessation self-efficacy, and being more autonomously motivated to quit smoking
      explained 67% of variance in commitment to stop smoking (P < .001). At 3 months,
      of 54 women responding, only 8 had quit smoking. Women reported smoking fewer
      cigarettes per day at 3 months compared with baseline (paired t51 = 3.43, P <
      .01). Higher baseline cessation self-efficacy and lower CHD threat were
      predictors of SC at 3 months (chi2(4) = 18.67, n = 54; P = .001). CONCLUSIONS:
      Although commitment, motivation, and self-efficacy to stop smoking were high,
      perceived threat of CHD and future invasive CV interventions were high, and
      perceived barriers to SC were low, most women continued to smoke after their
      heart catheterization. Referrals for assistance from healthcare providers to
      decrease anxiety and nicotine dependence and to address ongoing challenges to SC
      are needed.

PMID- 23001067
TI  - Aldosterone antagonists in heart failure.
AB  - BACKGROUND: Chronic, systolic heart failure is an increasing and costly health
      problem, and treatments based on pathophysiology have evolved that include the
      use of aldosterone antagonists. PURPOSE: Advances in the understanding of
      neurohormonal responses to heart failure have led to better pharmacologic
      treatments. The steroid hormone aldosterone has been associated with detrimental
      effects on the cardiovascular system, such as ventricular remodeling and
      endothelial dysfunction. This article will review the literature and guidelines
      that support the use of aldosterone antagonists in the treatment of chronic,
      systolic heart failure. CONCLUSIONS: Aldosterone antagonists are life-saving
      drugs that have been shown to decrease mortality in patients with New York Heart
      Association class III to IV heart failure and in patients with heart failure
      after an acute myocardial infarction. Additional studies are being conducted to
      determine if the role of aldosterone antagonists can be expanded to patients with
      less severe forms of heart failure. CLINICAL IMPLICATIONS: Aldosterone
      antagonists are an important pharmacologic therapy in the neurohormonal blockade
      necessary in the treatment of systolic heart failure. These drugs have been shown
      to decrease mortality and reduce hospital readmission rates. The major
      complication of aldosterone antagonists is hyperkalemia, which can be avoided
      with appropriate patient selection and diligent monitoring.

PMID- 23001068
TI  - Microplasmin (ocriplasmin) in pediatric vitreoretinal surgery: update and review.
AB  - PURPOSE: To discuss the potential role of microplasmin (ocriplasmin) as a
      surgical adjunct to vitrectomy in pediatric vitreoretinopathies. METHODS:
      Literature review of the laboratory and clinical evidence to date for the use of
      both autologous plasmin enzyme as an adjunct to vitrectomy and more recently
      recombinant microplasmin (ocriplasmin) as monotherapy for focal vitreomacular
      traction in adults. RESULTS: Autologous plasmin enzyme is currently being used as
      a surgical adjunct to vitrectomy, with supporting Levels 2 and 3 published
      evidence in a range of pediatric vitreoretinopathies including Stage 5
      retinopathy of prematurity and congenital X-linked retinoschisis. The
      availability of autologous plasmin enzyme is limited. In recent Phase 3 clinical
      trials, intravitreal ocriplasmin versus sham injection resulted in resolution of
      focal vitreomacular traction in 27% versus 10% (P < 0.001, n = 652). CONCLUSION:
      Ocriplasmin may potentially be used as a surgical adjunct to vitrectomy in place
      of autologous plasmin enzyme. A Phase 2, randomized, placebo-controlled surgical
      trial is under way to assess this.

PMID- 23001070
TI  - Reendothelialization of human heart valve neoscaffolds using umbilical cord
      derived endothelial cells.
AB  - BACKGROUND: Heart valve tissue engineering represents a concept for improving the
      current methods of valvular heart disease therapy. The aim of this study was to
      develop tissue engineered heart valves combining human umbilical vein endothelial
      cells (HUVECs) and decellularized human heart valve matrices. METHODS AND
      RESULTS: Pulmonary (n=9) and aortic (n=6) human allografts were harvested from
      explanted hearts from heart transplant recipients and were decellularized using a
      detergent-based cell extraction method. Analysis of decellularization success was
      performed with light microscopy, transmission electron microscopy and
      quantitative analysis of collagen and elastin content. The decellularization
      method resulted in full removal of native cells while the mechanical stability
      and the quantitative composition of the neoscaffolds was maintained. The luminal
      surface of the human matrix could be successfully recellularized with in vitro
      expanded HUVECs under dynamic flow conditions. The surface appeared as a
      confluent cell monolayer of positively labeled cells for von Willebrand factor
      and CD 31, indicating their endothelial nature. CONCLUSIONS: Human heart valves
      can be decellularized by the described method. Recellularization of the human
      matrix resulted in the formation of a confluent HUVEC monolayer. The in vitro
      construction of tissue-engineered heart valves based on decellularized human
      matrices followed by endothelialization using HUVECs is a feasible and safe
      method, leading to the development of future clinical strategies in the treatment
      of heart valve disease.

PMID- 23001069
TI  - A systematic review of the psychosocial difficulties relevant to patients with
      migraine.
AB  - Migraine is a common disease which causes significant burden to individuals, in
      terms of personal suffering and activity reduction, and to societies, in terms of
      disease cost. The purpose of this study is to identify the most relevant
      psychosocial difficulties related to migraine, the variables associated with them
      and the most relevant determinants of their evolution over time.  MEDLINE and
      PsychINFO were searched for studies published in English between 2000 and 2010
      that examined psychosocial difficulties in persons with migraine with and without
      aura, from clinical trials and observational studies. Information on the
      description of each difficulty, its determinants of onset and change over time
      and associated variables were extracted and categorized at a higher level. In
      total, 34 difficulties have been collected from 51 papers: the most frequent were
      reduced vitality and fatigue, emotional problems, pain, difficulties at work,
      general physical and mental health, social functioning and global disability.
      Evidence exists that pharmacological treatments have an impact toward improvement
      in patients' difficulties, in particular emotional problems, physical and mental
      health, difficulties with employment and global disability. Migraine treatments
      and decreased headaches frequency are the major determinants of improvements in
      psychosocial difficulties, while no information is available for determinants of
      worsening; understanding the role of such factors is of primary public health
      relevance, given the high prevalence and the relevant personal and societal costs
      of migraine.

PMID- 23001071
TI  - Structural valve deterioration in a starr-edwards mitral caged-disk valve
      prosthesis.
AB  - BACKGROUND: The durability of the Starr-Edwards (SE) mitral caged-disk valve,
      model 6520, is not clearly known, and structural valve deterioration in the SE
      disk valve is very rare. METHODS AND RESULTS: Replacement of the SE mitral disk
      valve was performed in 7 patients 23-40 years after implantation. Macroscopic
      examination of the removed disk valves showed no structural abnormalities in 3
      patients, in whom the disk valves were removed at <26 years after implantation.
      Localized disk wear was found at the sites where the disk abutted the struts of
      the cage, in disk valves excised >36 years after implantation in 4 patients. Disk
      fracture, a longitudinal split in the disk along its circumference at the site of
      incorporation of the titanium ring, was detected in the valves removed 36 and 40
      years after implantation, respectively, and many cracks were also observed on the
      outflow aspect of the disk removed 40 years after implantation. CONCLUSIONS: Disk
      fracture and localized disk wear were found in the SE mitral disk valves
      implanted >36 years previously. The present results suggest that SE mitral caged
      disk valves implanted >20 years previously should be carefully followed up, and
      that those implanted >30 years previously should be electively replaced with
      modern prosthetic valves

PMID- 23001072
TI  - Comparative review of functional outcomes post surgery for Hirschsprung's disease
      utilizing the paediatric incontinence and constipation scoring system.
AB  - PURPOSE: We aim to analyze differences in functional outcomes in children
      operated on for Hirschsprung's disease (HD) using the Paediatric
      incontinence/constipation scoring system (PICSS) validated in a normative group.
      METHODS: A retrospective review of the records of all children operated on for HD
      between 1997 and 2010 was performed. Patients had either a Soave or transanal
      endorectal pull-through. Children with total colonic aganglionosis and Down's
      syndrome were excluded. Utilizing the PICSS children who scored below their age
      specific lower limit 95 % confidence interval PICSS scores were considered to
      have incomplete continence or constipation. The rates of incomplete continence
      and constipation were compared between groups. Significance was set at p < 0.05.
      RESULTS: PICSS analysis could be completed in 51 (Soave 35, transanal 16). The
      median age at interview was 71 months (range 6-191 months). The rate of
      incomplete continence was 75 % (n = 21) and 71 % (n = 10) for the Soave and
      transanal groups, respectively (p = 1.00). The constipation rate was 34 % (n =
      12) and 25 % (n = 4) for the Soave and transanal groups, respectively (p = 0.74).
      The overall rates of incomplete continence and constipation rates were 74 and 31
      %, respectively, compared with 14 and 10 %, respectively, when rates were
      calculated by review of records. CONCLUSION: The PICSS is a sensitive tool for
      assessing functional outcome post HD surgery. The Soave and transanal procedures
      have similar functional outcomes.

PMID- 23001073
TI  - Evaluating the behaviour of different thermal indices by investigating various
      outdoor urban environments in the hot dry city of Damascus, Syria.
AB  - Consideration of urban microclimate and thermal comfort is an absolute neccessity
      in urban development, and a set of guidelines for every type of climate must be
      elaborated. However, to develop guidelines, thermal comfort ranges need to be
      defined. The aim of this study was to evaluate the behaviour of different thermal
      indices by investigating different thermal environments in Damascus during summer
      and winter. A second aim was to define the lower and upper limits of the thermal
      comfort range for some of these indices. The study was based on comprehensive
      micrometeorological measurements combined with questionnaires. It was found that
      the thermal conditions of different outdoor environments vary considerably. In
      general, Old Damascus, with its deep canyons, is more comfortable in summer than
      modern Damascus where there is a lack of shade. Conversely, residential areas and
      parks in modern Damascus are more comfortable in winter due to more solar access.
      The neutral temperatures of both the physiologically equivalent temperature (PET)
      and the outdoor standard effective temperature (OUT_SET*) were found to be lower
      in summer than in winter. At 80 % acceptability, the study defined the lower
      comfort limit in winter to 21.0  degrees C and the upper limit in summer to 31.3 
      degrees C for PET. For OUT_SET*, the corresponding lower and upper limits were
      27.6  degrees C and 31.3  degrees C respectively. OUT_SET* showed a better
      correlation with the thermal sensation votes than PET. The study also highlighted
      the influence of culture and traditions on people's clothing as well as the
      influence of air conditioning on physical adaptation.

PMID- 23001074
TI  - Murine gut microbiota and transcriptome are diet dependent.
AB  - OBJECTIVE: Here, we determine how formula feeding impacts the gut microbiota and
      host transcriptome. BACKGROUND: Formula-fed (FF) infants are at risk for diseases
      that involve complex interactions between microbes and host immune elements such
      as necrotizing enterocolitis. The aims of this study were to simultaneously
      examine the microbiota and host transcriptional profiles of FF and maternal-fed
      (MF) mice to evaluate how diet impacts gut colonization and host genes. METHODS:
      After 72 hours of FF or MF, colonic tissue was collected. 16S ribosomal RNA was
      sequenced with Roche GS-FLX (Genome Sequencer-FLX) pyrosequencing. Operational
      taxonomical unit clustering, diversity analysis, and principal coordinate
      analysis (PCA) were performed. Complementary DNA libraries were sequenced by
      Solexa. Reads were annotated by BLAST (Basic Local Alignment Search Tool) search
      against mouse RNA database [National Center for Biotechnology Information (NCBI)
      build-37] and functionally classified using the KOG (Eukaryotic Orthologous
      Groups) database (NCBI). RESULTS: Firmicutes (P < 0.001) was the dominant phylum
      in MF pups, whereas Proteobacteria (P < 0.001) and Bacteroidetes (P < 0.05) were
      dominant in FF mice. On the genus level, FF mice had increased Serratia (P <
      0.001) and Lactococcus (P < 0.05) whereas MF mice had increased Lactobacillus (P
      < 0.001). PCA confirmed clustering by diet. Solexa sequencing demonstrated
      different (P < 0.05) messenger RNA transcript levels in 148 genes. Heme oxygenase
      1 (P < 0.01), an oxidative stress marker, was increased 25-fold in FF mice. In
      addition, decreased vinculin (P < 0.05), a cytoskeletal protein associated with
      adherens junctions in FF pups suggested impaired gut structural integrity. Diet
      also impacted immune regulation, cell cycle control/gene expression, cell
      motility, and vascular function genes. CONCLUSIONS: FF shifted gut microbiota and
      structural integrity, oxidative stress, and immune function genes, presumably
      increasing vulnerability to disease in FF mice. Interrogation of microbial and
      host gene expression in FF neonates may offer new insight on how diet affects
      disease pathogenesis.

PMID- 23001075
TI  - Impact of robotic surgery on sexual and urinary functions after fully robotic
      nerve-sparing total mesorectal excision for rectal cancer.
AB  - BACKGROUND: Urinary and sexual dysfunctions are recognized complications of
      rectal cancer surgery. Their incidence after robotic surgery is as yet unknown.
      The aim of this study was to prospectively evaluate the impact of robotic surgery
      for rectal cancer on sexual and urinary functions in male and female patients.
      METHODS AND PROCEDURES: From April 2008 to December 2010, 74 patients undergoing
      fully robotic resection for rectal cancer were prospectively included in the
      study. Urinary and sexual dysfunctions affecting quality of life were assessed
      with specific self-administered questionnaires in all patients undergoing robotic
      total mesorectal excision (RTME). Results were calculated with validated scoring
      systems and statistically analyzed. RESULTS: The analyses of the questionnaires
      completed by the 74 patients who underwent RTME showed that sexual function and
      general sexual satisfaction decreased significantly 1 month after intervention:
      19.1 +/- 8.7 versus 11.9 +/- 10.2 (P < 0.05) for erectile function and 6.9 +/-
      2.4 versus 5.3 +/- 2.5 (P < 0.05) for general satisfaction in men; 2.6 +/- 3.3
      versus 0.8 +/- 1.4 (P < 0.05) and 2.4 +/- 2.5 versus 0.7 +/- 1.6 (P < 0.05) for
      arousal and general satisfaction, respectively, in women. Subsequently, both
      parameters increased progressively, and 1 year after surgery, the values were
      comparable to those measured before surgery. Concerning urinary function, the
      grade of incontinence measured 1 year after the intervention was unchanged for
      both sexes. CONCLUSIONS: RTME allows for preservation of urinary and sexual
      functions. This is probably due to the superior movements of the wristed
      instruments that facilitate fine dissection, coupled with a stable and magnified
      view that helps in recognizing the inferior hypogastric plexus.

PMID- 23001076
TI  - Race and surgical residency: results from a national survey of 4339 US general
      surgery residents.
AB  - OBJECTIVE: To determine how race influences US general surgery residents'
      experiences during residency training. BACKGROUND: Minorities are
      underrepresented in medicine, particularly surgery, with no large-scale studies
      investigating their training experiences. METHODS: Cross-sectional national
      survey administered after the 2008 American Board of Surgery In-Training
      Examination to all categorical general surgery residents. Demographic
      characteristics and survey responses with respect to race were evaluated using
      the chi test and hierarchical logistic regression modeling. RESULTS: A total of
      4339 residents were included: 61.9% whites, 18.5% Asians, 8.5% Hispanics, 5.3%
      Blacks, and 5.8% Others. Minorities differed from whites in sex proportion,
      marital status, number of children, geographic location, type of residency
      program, and 24 survey items (all Ps < 0.05). Compared with white residents,
      Black, Asian, and Other residents were less likely to feel they fit in at their
      programs (86.2% vs 73.9%, 83.3%, and 81.2%, respectively; P < 0.001). Black and
      Asian residents were more likely to report that attendings would think worse of
      them if they asked for help (13.5% vs 20.4% and 18.4%, respectively; P = 0.002),
      and Black residents were less likely to feel they could count on their peers for
      help (85.2% vs 77.2%; P = 0.017). On hierarchical logistic regression modeling,
      Blacks were least likely to fit in at their programs (odds ratio = 0.6; P =
      0.004), and all minorities were more likely to feel that there was a need for
      additional specialty training (odds ratio = 1.4 Blacks and Hispanics, 1.9 Asians,
      and 2.1 Others; all Ps <= 0.05). CONCLUSIONS: Minority residents report less
      positively on program fit and relationships with faculty and peers. Future
      studies should focus on examining residency interventions to improve support and
      integration of minority residents.

PMID- 23001077
TI  - Liver stiffness measurement by transient elastography as a predictor on
      posthepatectomy outcomes.
AB  - BACKGROUND: Liver fibrosis and cirrhosis are well-known risk factors for
      morbidity after hepatectomy. Liver stiffness measurement (LSM) using transient
      elastography is a new method for detection of hepatic fibrosis and cirrhosis with
      high accuracy. Whether LSM can predict posthepatectomy outcomes has not been
      studied. METHODS: This was a prospective cohort study in which consecutive
      patients underwent hepatectomy for various indications from February 2010 to July
      2011. All patients received detailed preoperative assessments including LSM and
      indocyanine green (ICG) clearance test. The primary outcome was major
      postoperative complication. RESULTS: One hundred five patients with a mean age of
      59 years were included; 75 (71.4%) had chronic viral hepatitis and 76 (72.4%) had
      hepatocellular carcinoma. Thirty-four patients (32.4%) received major
      hepatectomy. The median ICG retention rate at 15 minutes was 4.2 (0.1%-32%) and
      the median LSM was 9.4 (3.3-75 kPa). For posthepatectomy outcomes, only LSM but
      not ICG showed significant correlation with major postoperative complications on
      receiver operating characteristic curves, with area under the curve of 0.79 (P <
      0.001). Using the calculated cutoff at 12.0 kPa, LSM had sensitivity of 85.7% and
      specificity of 71.8% in the prediction of major postoperative complications. It
      was also an independent prognostic factor for major postoperative complications
      by multivariate analysis. The operative blood loss and transfusion rate were also
      significantly higher in patients with LSM >12.0 kPa. CONCLUSIONS: High LSM (>12.0
      kPa) predicted worse posthepatectomy outcomes. Preoperative LSM was better than
      ICG test in the prediction of major postoperative complications. It was a useful
      preoperative investigation for risk stratification before hepatectomy.

PMID- 23001078
TI  - A novel nomogram accurately quantifies the risk of mortality in elderly patients
      undergoing colorectal surgery.
AB  - OBJECTIVE: The ability to accurately predict postoperative mortality is expected
      to improve preoperative decisions for elderly patients considered for colorectal
      surgery. METHODS: Patients undergoing colorectal surgery were identified from the
      National Surgical Quality Improvement Program database (2005-2007) and stratified
      as elderly (>70 years) and nonelderly (<70 years). Univariate analysis of
      preoperative risk factors and 30-day mortality and morbidity were analyzed on 70%
      of the population. A nomogram for mortality was created and tested on the
      remaining 30%. RESULTS: Of 30,900 colorectal cases, 10,750 were elderly (>70
      years). Mortality increased steadily with age (0.5% every 5 years) and at a
      faster rate (1.2% every 5 years) after 70 years, which defined "elderly" in this
      study. Elderly (mean age: 78.4 years) and nonelderly patients (52.8 years) had
      mortality of 7.6% versus 2.0% and a morbidity of 32.8% versus 25.7%,
      respectively. Elderly patients had greater preoperative comorbidities including
      chronic obstructive pulmonary disease (10.5% vs 3.8%), diabetes (18.7% vs 11.1%),
      and renal insufficiency (1.7% vs 1.3%). A multivariate model for 30-day mortality
      and nomogram were created. Increasing age was associated with mortality [age >70
      years: odds ratio (OR) = 2.0 (95% confidence interval (CI): 1.7-2.4); >85 years:
      OR = 4.3 (95% CI: 3.3-5.5)]. The nomogram accurately predicted mortality,
      including very high-risk (>50% mortality) with a concordant index for this model
      of 0.89. CONCLUSIONS: Colorectal surgery in elderly patients is associated with
      significantly higher mortality. This novel nomogram that predicts postoperative
      mortality may facilitate preoperative treatment decisions.

PMID- 23001079
TI  - Sacral nerve stimulation at subsensory threshold does not compromise treatment
      efficacy: results from a randomized, blinded crossover study.
AB  - BACKGROUND AND OBJECTIVE: : Stimulation amplitude used in sacral nerve
      stimulation (SNS) is at or just above the sensory threshold (ST). This
      randomized, blinded crossover study aimed to document if stimulation at 75% or
      50% of the ST would be as effective as stimulation at the ST for fecal
      incontinence (FI). METHOD: : FI patients treated with SNS, who were satisfied
      with current treatment results and had a minimum symptom reduction of 75%, were
      eligible. Patients were randomized into 3 periods of 4-week stimulation: ST, 75%
      of the ST, and 50% of the ST. Patients completed a bowel habit diary and
      questionnaires on bowel functions and patient satisfaction at the study baseline
      and in each study period. RESULTS: : Nineteen patients (18 females) with a mean
      follow-up of 51.7 +/- 29.9 months were included from January to April 2010. The
      mean FI episodes per 3 weeks decreased from pre-SNS therapy 33.6 +/- 31.6 to 1.1
      +/- 2.2 at the study baseline (P < 0.001). Decreasing the stimulation amplitude
      to as low as 50% of the ST did not affect the overall number of incontinent
      episodes (P = 0.078). The Wexner incontinence score dropped from 16.5 +/- 2.5 for
      pre-SNS therapy to 7.4 +/- 3.1 at the study baseline (P < 0.001). Decreasing the
      stimulation amplitude to ST, 75% of the ST or 50% of the ST, did not change the
      Wexner score when compared with the study baseline (P = 0.581). In general,
      patient satisfaction was high at the study baseline and did not deteriorate as
      the stimulation amplitude was decreased to 50% of the ST (P = 0.932).
      CONCLUSIONS: : Subsensory stimulation as low as 50% of the ST is as effective as
      stimulation at or above the ST. The study was approved by the Regional Committee
      on Biomedical Research Ethics, Denmark, and registered at ClinicalTrials.gov
      (NCT01130870).

PMID- 23001080
TI  - Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the
      prognostic impact of histological grade.
AB  - PURPOSE: Though histological grade is known to have a major prognostic impact in
      metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade
      in localized disease, and the validity of the American Joint Committee on Cancer
      AJCC Staging Manual 7th edition's decision to combine moderately and poorly
      differentiated mucinous adenocarcinomas into a single mucinous high-grade
      category, is not known. METHODS: Patients with adenocarcinoma of the appendix
      diagnosed between 1988 and 2007 were identified from the SEER database. Cancer
      specific survival (CSS) stratified by histological subtype, stage, and grade was
      calculated, and Cox proportional hazards regression analyses were performed.
      RESULTS: We analyzed a total of 2469 appendiceal adenocarcinomas, of which 1375
      had mucinous histology and 860 had nonmucinous histology. Though overall CSS was
      similar for mucinous and nonmucinous subtypes, differences in stage distribution
      and stage-stratified CSS were seen. Female sex, stage IV disease, and well
      differentiated histology were more common for mucinous adenocarcinomas.
      Histological grade had a strong prognostic impact, especially in patients with
      stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV
      moderately and poorly differentiated histological grade were 1.63 [95% confidence
      interval (CI): 1.14-2.34] and 4.94 (95% CI: 3.32-7.35) for mucinous histology, in
      comparison with 1.44 (95% CI: 0.82-2.52) and 1.90 (95% CI: 0.95-3.80) for
      nonmucinous histology, respectively. CONCLUSIONS: The strong prognostic impact of
      histological grade for mucinous adenocarcinomas is primarily restricted to stage
      IV disease. Stage IV moderately and poorly differentiated mucinous
      adenocarcinomas have distinctly different CSS and these data do not support the
      combination of these 2 histological grades in the recent AJCC Staging Manual 7th
      edition.

PMID- 23001081
TI  - Esophagectomy using a thoracoscopic approach with an open laparotomic or hand
      assisted laparoscopic abdominal stage for esophageal cancer: analysis of survival
      and prognostic factors in 315 patients.
AB  - Survival and prognostic factors were analyzed in 315 patients with esophageal
      cancer undergoing thoracoscopic-assisted esophagectomy (TAE). The 5-year survival
      rate of 57.8% was satisfactory, indicating the oncological feasibility of TAE.
      Perioperative outcomes affected overall survival in the whole cohort but not in
      the subgroup treated with 2 endoscopic stages. OBJECTIVE: To estimate the
      oncological feasibility of thoracoscopic-assisted esophagectomy (TAE) for
      esophageal cancer and to clarify the prognostic impact of perioperative factors
      after TAE. BACKGROUND: Favorable perioperative outcomes of TAE versus open
      surgery have been demonstrated. However, survival data after TAE in a large
      cohort are limited, and no information on the prognostic influence of
      perioperative factors after TAE is available. METHODS: Prospectively collected
      data for 315 patients undergoing TAE for esophageal cancer were analyzed.
      Survival was compared with the Kaplan-Meier analysis and Cox regression analysis
      between 2 surgical approaches: thoracoscopic and hand-assisted laparoscopic
      esophagectomy (THLE) and thoracoscopic and open laparotomic esophagectomy (TOE).
      Factors affecting overall survival were identified with Cox multivariate
      regression analysis in the whole cohort and the THLE subgroup. RESULTS: THLE and
      TOE were performed in 153 and 162 patients, respectively. The overall 5-year
      survival of the whole cohort was 57.8%, with no difference between the THLE and
      the TOE group. Multivariate analysis of the 315 patients identified the following
      prognostic factors: blood loss, blood transfusion, intensive care unit stay,
      cardiovascular complications, pathological T and N stages, lymphatic invasion,
      intramural metastasis, and number of metastatic nodes. In the THLE subgroup,
      cerebral comorbidity, histological subtype, pathological T stage, and number of
      metastatic nodes were independent prognostic factors. CONCLUSIONS: TAE was
      oncologically feasible. Perioperative factors affected survival in the whole
      cohort, but did not in the THLE subgroup. However, the reduced perioperative
      factor effect in this subgroup would be small because the survival rates of the 2
      surgical approaches were equal.

PMID- 23001082
TI  - Efficacy of prophylactic antibiotic administration for breast cancer surgery in
      overweight or obese patients: a randomized controlled trial.
AB  - OBJECTIVE: To assess the impact of prophylactic antibiotics on the prevention of
      surgical site infection (SSI) and the cost-effectiveness of this prophylaxis for
      breast cancer surgery in overweight or obese women. BACKGROUND DATA: SSI is
      higher than expected after breast surgery. Obesity was found to be one of the
      risk factors. METHODS: The trial was designed as a phase IV randomized,
      controlled, parallel-group efficacy trial. It was conducted at a tertiary
      university hospital. Overweight or obese women with clinically early-stage breast
      cancer who had been assigned to undergo surgery were eligible. Patients were
      randomly allocated to either a prophylaxis or a control group by using a computer
      generated list. The prophylaxis group received 1 g ampicillin-sulbactam
      intravenously at anesthesia. The control group received no intervention. Patients
      and observers were blinded to the assignments. The primary outcome was the
      comparison of SSI incidences of the 2 groups. Patients were monitored for 30
      days. RESULTS: A total of 369 patients were included in final analysis, out of
      which 187 were allocated for prophylaxis and 182 were randomly assigned to the
      control group. Analysis was done according to the intention-to-treat principle.
      Prophylaxis significantly reduced the SSI rate (4.8%) in the prophylaxis group
      when compared with that in the control group [13.7%; relative risk (RR) 0.35; 95%
      CI: 0.17-0.73]. No adverse reaction was observed. The mean SSI-related cost
      (20.26 USD) was found to be significantly higher in the control group when
      compared with that (8.48 USD) in the prophylaxis group. CONCLUSION: Antibiotic
      prophylaxis significantly decreased SSI incidence after elective surgery and was
      shown to be cost-effective in obese breast cancer patients. ClinicalTrials.gov
      Identifier: NCT00356148.

PMID- 23001083
TI  - The entire small intestine mediates the changes in glucose homeostasis after
      intestinal surgery in Goto-Kakizaki rats.
AB  - OBJECTIVE: To investigate the potential interaction between excluding foregut and
      interposing hindgut and the role of different portions of the small intestine in
      mediating changes in some glucoregulatory mechanisms and glucose homeostasis
      after intestinal surgery in Goto-Kakizaki (GK) rats. BACKGROUND: Previous studies
      have revealed changes in glucoregulatory mechanisms and glucose homeostasis after
      excluding foregut and interposing hindgut alone and lead to the "foregut
      hypothesis" and "hindgut hypothesis." However, these hypotheses are not mutually
      exclusive. METHODS: Duodenal-jejunal bypass (DJB), ileal interposition (IT),
      duodenal-jejunal bypass with ileal interposition (DJBIT), sub-ileal interposition
      (sIT), and sham operations were performed on GK rats. Main outcome measures were
      oral glucose tolerance (studied at 0, 2, 4, 8, and 24 weeks), insulin
      sensitivity, beta-cell function, and postprandial levels of glucagon-like peptide
      1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic peptide(GIP)
      (evaluated at 2 and 24 weeks). RESULTS: Global body weight in the control group
      was higher than in the operation groups at postoperative week 2, but it was
      similar among groups at postoperative week 24. The DJBIT procedure induced
      synergistic improvement in glucose tolerance and insulin sensitivity (P < 0.05).
      Generalized linear mixed-model analysis confirmed that glucose tolerance in
      nonsham operation groups improved over time (P < 0.001), with a significant time
      * treatment interaction (P < 0.001). Fasting C-peptide, postprandial insulin, GLP
      1, and PYY levels increased after nonsham operations (P < 0.05); however, they
      were not significantly different among the DJBIT, DJB, and IT groups (P > 0.05).
      Compared with sub-IT, IT induced better glucose tolerance (P < 0.05) and higher
      postprandial insulin, GLP-1 and PYY levels (P < 0.05), and no significant
      difference in insulin sensitivity and fasting C-peptide was observed (P > 0.05).
      None of the surgical procedures affected glucose-stimulated GIP levels (P >
      0.05). CONCLUSIONS: This study provides experimental evidence that excluding
      foregut and interposing hindgut provided independent and synergistic changes in
      glucose homeostasis after intestinal surgery in GK rats and that glucose
      tolerance improved over time.

PMID- 23001084
TI  - Hand-sewn versus mechanical esophagogastric anastomosis after esophagectomy: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the risks and benefits of using a circular stapler (CS)
      compared with the hand-sewn (HS) method for the esophagogastric anastomosis after
      esophageal resection. BACKGROUND DATA: Previous randomized controlled trials
      (RCTs) indicated that the use of a CS might prevent anastomotic leakage, whereas
      it was more likely to lead to anastomotic strictures. The relative efficacy of
      this intervention in comparison with the HS method has not been conclusively
      determined. METHODS: A systematic review and meta-analysis of all RCTs that
      compared HS versus mechanical anastomosis using a CS was conducted regarding the
      leakage, strictures, operative time, and mortality. The study protocol was
      established a priori according to the recommendations of the Cochrane
      Collaboration. RESULTS: Twelve RCTs were included with a total of 1407 patients.
      The use of a CS, compared with the HS method, (1) led to no significant
      difference in the incidence of anastomotic leakage [risk ratio (RR): 1.02, 95%
      confidence interval (CI): 0.66-1.59] or postoperative mortality (RR: 1.64, 95%
      CI: 0.95-2.83), (2) increased the incidence of anastomotic strictures (RR: 1.67,
      95% CI: 1.16-2.42), and (3) reduced the length of the operation time (mean: -15.3
      minutes, range: -28.1 to -2.39). For these results, a subgroup analysis and a
      meta-regression analysis yielded no significant differences for the anastomotic
      site, diameter of the CS, layer, or configuration. CONCLUSION: The use of a CS
      contributed to reducing the length of the operation, but was associated with an
      increased risk of anastomotic strictures. Both the CS and the HS method are
      viable alternatives in the reconstruction after esophagectomy.

PMID- 23001086
TI  - Abdominal aortic calcification and surgical outcomes in patients with no known
      cardiovascular risk factors.
AB  - INTRODUCTION: In the setting of cardiovascular (CV) risk evaluation before major
      elective surgery, current risk assessment tools are relatively poor for
      discriminating among patients. For example, patients with clinical CV risk
      factors can be clearly identified; but among those without appreciated clinical
      CV risk, there may be a subset with stigmata of CV disease noted during the
      preoperative radiographic evaluation. Our study evaluated the relationship
      between abdominal aortic (AA) calcification measured on preoperative computed
      tomography (CT) imaging and surgical complications in patients undergoing general
      elective and vascular surgery. We hypothesized that patients with no known CV
      risk factors but significant aortic calcification on preoperative imaging will
      have inferior surgical outcomes. METHODS: The study group included 1180 patients
      from the Michigan Surgical Quality Collaborative (MSQC) database who underwent
      major general or vascular elective surgery between 2006 and 2009 and who had a CT
      scan of the abdomen specifically for preoperative planning. AA calcification was
      measured using novel analytic morphomic techniques and reported as a percentage
      of the total wall area containing calcification. Patients were divided into
      cohorts by clinical CV risk and extent of AA calcification. Univariate analysis
      was used to compare postoperative morbidity between patient cohorts. Multivariate
      logistic regression analysis was used to compare continuous AA calcification with
      overall morbidity in patients with no clinical CV risk factors. RESULTS: AA
      calcification was strongly skewed to the right (53.5% had no AA calcification)
      and was significantly correlated with age (rho = 0.43, P < 0.001). Unadjusted
      univariate analysis of morbidity showed no significant differences in
      complication rates between patients in the clinical CV risk and significant AA
      calcification (no known CV risk factor) categories. The clinical CV risk (P <
      0.001) and significant AA calcification without CV risk factors (P = 0.009)
      populations both had significantly more infectious and overall complications than
      patients with no AA calcification and no clinical CV risk. Multivariate logistic
      regression confirmed that AA calcification was a significant predictor of
      morbidity in patients with no clinical CV risk factors (odds ratio = 1.35, P =
      0.017). DISCUSSION: This study suggests that AA calcification may be related to
      progression of CV disease and surgical outcomes. A better understanding of the
      complex interaction of patient physiology with overall ability to recover from
      major surgery, using novel approaches such as analytic morphomics, has great
      potential to improve risk stratification and patient selection.

PMID- 23001085
TI  - Upper-extremity transplantation using a cell-based protocol to minimize
      immunosuppression.
AB  - OBJECTIVE: To minimize maintenance immunosuppression in upper-extremity
      transplantation to favor the risk-benefit balance of this procedure. BACKGROUND:
      Despite favorable outcomes, broad clinical application of reconstructive
      transplantation is limited by the risks and side effects of multidrug
      immunosuppression. We present our experience with upper-extremity transplantation
      under a novel, donor bone marrow (BM) cell-based treatment protocol ("Pittsburgh
      protocol"). METHODS: Between March 2009 and September 2010, 5 patients received a
      bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2)
      hand transplant. Patients were treated with alemtuzumab and methylprednisolone
      for induction, followed by tacrolimus monotherapy. On day 14, patients received
      an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive
      follow-up included functional evaluation, imaging, and immunomonitoring. RESULTS:
      All patients are maintained on tacrolimus monotherapy with trough levels ranging
      between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients
      demonstrated sustained improvements in motor function and sensory return
      correlating with time after transplantation and level of amputation. Side effects
      included transient increase in serum creatinine, hyperglycemia managed with oral
      hypoglycemics, minor wound infection, and hyperuricemia but no infections.
      Immunomonitoring revealed transient moderate levels of donor-specific antibodies,
      adequate immunocompetence, and no peripheral blood chimerism. Imaging
      demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case.
      Protocol skin biopsies showed absent or minimal perivascular cellular
      infiltrates. CONCLUSIONS: Our data suggest that this BM cell-based treatment
      protocol is safe, is well tolerated, and allows upper-extremity transplantation
      using low-dose tacrolimus monotherapy.

PMID- 23001087
TI  - Prognostic factors after pulmonary metastasectomy for colorectal cancer and
      rationale for determining surgical indications: a retrospective analysis.
AB  - OBJECTIVE: We aimed to identify prognostic factors after pulmonary metastasectomy
      for colorectal cancer and propose the clinical application of them. Furthermore,
      we endeavored to provide a rationale for pulmonary metastasesectomy. BACKGROUND:
      Several prognostic factors have been proposed, but clinical application of them
      remains unclear. Moreover, there is no theoretical evidence that pulmonary
      metastasectomy is indicated for colorectal cancer. METHODS: We retrospectively
      analyzed 1030 patients who underwent pulmonary metastasectomy for colorectal
      cancer from 1990 to 2008. Prognostic factors were identified and the relationship
      of recurrent sites after pulmonary resection to pulmonary tumor size was
      assessed. RESULTS: Overall 5-year survival was 53.5%. Median survival time was
      69.5 months. Univariate analysis showed tumor number (P < 0.0001), tumor size (P
      < 0.0001), prethoracotomy serum carcinoembryonic antigen (CEA) level (P <
      0.0001), lymph node involvement (P < 0.0001), and completeness of resection (P <
      0.0001) to significantly influence survival. In multivariate analysis, all
      remained independent predictors of outcome. In patients whose recurrent sites
      extended downstream from the lung via hematogenous colorectal cancer spread,
      pulmonary tumor size was significantly larger than in those with recurrent sites
      confined to the lung and regions upstream from the lung. CONCLUSIONS: We should
      utilize these prognostic factors to detect patients who might benefit from
      surgery. Therefore, we should periodically follow up advanced colorectal cancer
      patients by chest computed tomography to detect small pulmonary metastases before
      serum CEA elevation. Metastases to the lung or organs upstream from the lung are
      regarded as semi-local for colorectal cancer. This concept provides a rationale
      for validating surgical indications for pulmonary metastases from colorectal
      cancer.

PMID- 23001088
TI  - Complete right lung agenesis presenting with bronchial asthma and allergic
      rhinitis.
AB  - A 26 year-old lady presented with episodic breathlessness, chest tightness,
      recurrent nasal obstruction and excessive sneezing, mainly during change of
      season along with opacity of the right hemithorax on chest x-ray. Further
      detailed work-up including spirometry, high-resolution CT scan of the thorax and
      fibre-optic bronchoscopy confirmed complete right lung agenesis in patients with
      bronchial asthma and allergic rhinitis. Complete control of symptoms was achieved
      with formeterol 6 MUg and mometasone 200 MUg (via dry powder inhaler) and
      intranasal fluticasone 50 MUg (nasal spray) 2 puffs twice daily and oral
      montelukast 10 mg with levocetirizine 5 mg once daily.

PMID- 23001089
TI  - A laparoscopic high anterior resection for sigmoid cancer with extraction through
      incarcerated left inguinal hernia repaired with Permacol mesh.
AB  - A 65-year-old man presented to the general surgical outpatients with an
      incarcerated left inguinal hernia. Initial investigations revealed an iron
      deficiency anaemia that was investigated with a colonoscopy and gastroscopy. This
      revealed a sigmoid cancer and the staging CT scan confirmed a tumour incarcerated
      in the sac of the left inguinal hernia. We proceeded with a laparoscopic high
      anterior resection using the inguinal hernia as the extraction site. The hernia
      was repaired using Permacol mesh. No postoperative complications occurred.

PMID- 23001090
TI  - Apathy and executive functions: insights from brain damage involving the anterior
      cingulate cortex.
AB  - Patients with anterior cingulate cortex (ACC) lesions present an opportunity for
      understanding apathy's disputed neuropsychiatric features, as well as its
      associated neurocognitive phenotype. In this case report, two male patients
      (patient A and patient B) with lesions involving the ACC bilaterally were
      assessed for apathy, depressive symptoms, executive functioning, and also tested
      on the Iowa Gambling Task (IGT). Twenty neurologically intact controls also
      provided normative scores on the IGT. Patient A and patient B had high scores for
      apathy and low depressive symptoms scores. Patient A had relatively intact
      performance on standard executive function tests, but patient B had significant
      impairments. Both patients were significantly impaired on the IGT. Our findings
      suggest that executive function deficits are not crucial for the presence of
      apathy symptoms. These findings not only shed light on the relationship between
      apathy and executive function deficits, but also have important implications for
      patient care and rehabilitation.

PMID- 23001091
TI  - Cerebrotendinous xanthomatosis: a rare disorder with a rare presentation.
AB  - A young man was brought for mental retardation, frequent non-bloody diarrhoea and
      swellings at ankles and elbow. He became bed-ridden due to cataract, mental
      retardation and pain in the back and lower limb. There were repeated pathological
      fractures and vitamin D deficiency without renal dysfunction. There were low low
      density lipoprotein and triglyceride levels. MRI of the brain revealed
      hypointense lesions in cerebellar white matter, heterogenous hyperintensity in
      dentate nucleus and adjacent white matter, right basal ganglia and in the
      periventricular region with diffuse cerebral atrophy. T1-weighted MRI (ankle
      region) revealed bilaterally thickened and irregular achilles tendons with
      hyperintense masses surrounded by patchy hypointensities. A similar xanthomatous
      lesion (cholestanol deposits) was also present in the sacral region. Vitamin D
      and calcium supplementation and chenodeoxycholic acid therapy improved pain at
      lower limbs and body weight. Cerebrotendinous xanthomatosis is a rare autosomal
      recessive familial mutation of the sterol 27 hydroxylase causing lipid metabolic
      disease.

PMID- 23001092
TI  - Hodgkin's lymphoma presents as an inguinal abscess: a case report and literature
      review.
AB  - Lymphadenitis with suppuration is a rare presentation of Hodgkin's lymphoma with
      few cases reported in the literature. We report two cases of Hodgkin's lymphoma
      in two male members of the same family. They presented initially with clinical
      features suggesting infective inguinal lymphadenitis and then the picture was
      indistinguishable from inguinal abscess. The diagnosis was made after drainage of
      the pus and excision of the involved lymph node. The histopathology of the
      excised lymph node showed Hodgkin's lymphoma-nodular sclerosis for both brothers.
      After careful staging of both patients, the disease found to be localised to the
      inguinal group of lymph nodes. The patients referred to the haematologist for
      chemotherapy and they recovered after treatment.

PMID- 23001093
TI  - Young stroke due to vascular anomaly from neurofibromatosis type 1.
AB  - Aetiology of stroke in young is often different to that of an older person. In
      nearly half of these cases no cause is established. Every effort should be
      explored to establish a cause as treatment varies accordingly and the prognosis
      with rehabilitation is favourable when compared with older people. We present a
      case of pontine infarct in a 43-year-old man due to vascular ectasia associated
      with neurofibromatosis type 1. Following the stroke, the patient went through
      intensive rehabilitation where he had a good functional outcome.

PMID- 23001094
TI  - A patient with tuberculous peritonitis with very high serum CA 125.
AB  - An 88-year-old woman presented with abdominal pain and distension. Serum cancer
      antigen 125 (CA 125) level was very high; however, abdominal CT reveals ascites
      without definite mass. Ascites analysis revealed a lymphocytic exudate with high
      adenosine deaminase enzyme level, negative stains for bacteria and negative PCR
      for Mycobacterium tuberculosis. Presumptive diagnosis for tuberculous peritonitis
      was made and antituberculous therapy resulted in the resolution of ascites and
      normalisation of CA 125.

PMID- 23001095
TI  - A likely diagnosis of Crohn's disease in a 95-year-old woman.
AB  - Crohn's disease (CD) has a bimodal distribution in incidence, with a second peak
      in the elderly. However, its diagnosis in the elderly is difficult due to a wider
      range of more common differential diagnoses such as diverticulitis, ischaemic
      colitis and colorectal cancer. We report a likely case of CD in a 95-year-old
      woman. She presented with diarrhoea and rectal bleeding and was found to have
      multiple pleomorphic ulcers with a patchy cobblestone mucosa on sigmoidoscopy.
      Histopathology demonstrated focal ulceration, altered crypt architecture and
      adjacent neutrophil polymorph infiltration with no granolomata or features of
      malignancy. The patient passed away after steroid treatment was started. This
      case is a reminder that CD can present in the elderly and highlights the
      challenging diagnosis and high mortality of CD-related hospitalisation in the
      elderly. When considering management, attention should be given to comorbid
      disease, age-related changes in pharmacokinetics and patients social
      circumstances.

PMID- 23001096
TI  - Tachycardia-induced cardiomyopathy.
AB  - Tachycardia-induced cardiomyopathy (TIC) is an important cause of heart failure
      as it is potentially reversible after ventricular rate control. A 66-year-old
      hypertensive woman presented with a 15-day history of tachycardia, dyspnoea and
      oedema. ECG revealed atrial fibrillation with ventricular frequency of 130 beats
      per minute (bpm). Echocardiogram showed dilated left ventricle (LV) with 0.39
      ejection fraction. Angiography revealed non-obstructed coronary arteries. Heart
      rate and cardiac failure were controlled with amiodarone, digoxine, captopril,
      metoprolol and furosemide. During follow-up, despite drug dose optimisation, the
      patient kept complaining of tachycardia and dyspnoea with a ventricular rate
      between 108 and 120&emsp14;bpm. Medical staff suspected she was not taking her
      medicines properly. Two months later, the patient was asymptomatic and had
      converted to sinus rhythm (heart rate of 76&emsp14;bpm). Echocardiogram showed
      normal LV size and function. Patient's diagnosis was TIC. Although rare, TIC
      should be considered in all cases of systolic dysfunction associated with
      tachyarrhythmia.

PMID- 23001097
TI  - Lipomatous hypertrophy of interatrial septum.
AB  - Lipomatous hypertrophy of the interatrial septum is being increasingly recognised
      and should be considered as part of the differential diagnosis for any cardiac
      tumour. We present the case of a 65-year-old male patient who presented at the
      emergency department complaining of palpitations. Transthoracic and
      transoesophageal echocardiography detected a lipomatous membrane separating the
      dilated left atrium from the right atrium. Diagnosis was confirmed by MRI. In
      such cases, the opinion of a specialist echocardiologist would help to avoid a
      misdiagnosis and unnecessary intervention.

PMID- 23001098
TI  - Sulphadiazine-induced renal stones in a 63-year-old HIV-infected man treated for
      toxoplasmosis.
AB  - A 63-year-old man was admitted for investigation of blurred vision and multiple
      ring-enhancing lesions on cranial MRI. Histopathological examination of tissue
      obtained at brain biopsy showed multiple Toxoplasma gondii cysts. He was started
      on a combination of sulphadiazine and pyrimethamine for cerebral toxoplasmosis
      and was subsequently diagnosed with HIV-1 infection. He then developed acute
      renal failure and flank pain and was diagnosed with bilateral vesico-uretric
      calculi requiring bilateral stent insertion. The retrieved renal calculi were
      negative for the common stones that are routinely tested for in our laboratory
      and had the macroscopic characteristics of a sulphadiazine stone. His renal
      failure responded to cessation of the sulphadiazine.

PMID- 23001099
TI  - Rosai Dorfman disease: appearances can be deceptive.
AB  - A 14-year-old boy was referred to us with a history of progressive painless
      massive symmetrical cervical lymphadenopathy, provisionally diagnosed as
      lymphoma. Multiple biopsies were needed, and confirmed the diagnosis of Rosai
      Dorfman disease (RDD), which is a very rare benign condition. Sinus histiocytosis
      with massive lymphadenopathy, also known as RDD, manifests as bulky
      lymphadenopathy in children and young adults. Extranodal sites such as the skin,
      upper airways, gastrointestinal tract and central nervous system can be involved.
      There is a characteristic pattern of lymphoid proliferation with a thick fibrous
      capsule, distention of lymphoid sinuses, accumulation of plasma cells and
      proliferation of large, often atypical, histiocytes showing emperipolesis is
      characteristic. The disease is considered to be benign and usually self-limited.
      We emphasise the need for doing a repeat lymphnode biopsy even if the prior
      histopathology is suggestive of reactive lypmhnode hyperplasia in every case of
      persisting lymphadenopathy.

PMID- 23001100
TI  - Successful deep anterior lamellar keratoplasty following multiple failed limbal
      transplantations for chronic ocular burns.
AB  - A 9-year-old girl with severe unilateral ocular surface disease due to limbal
      stem cell deficiency following chemical injury underwent autologous cultivated
      limbal epithelial transplantation (CLET) twice in her right eye that failed to
      improve the condition of the ocular surface. On both occasions, limbal biopsies
      were obtained from the unaffected left eye. Since further attempts at CLET were
      not considered to be safe, deep anterior lamellar keratoplasty (DALK) was
      performed instead. DALK was complicated by postoperative Descemet's membrane
      detachment, which was successfully treated. Two years post-DALK the patient had a
      clear graft, stable ocular surface and visual acuity of 20/80. The mechanism by
      which CLET allows a patient to repopulate the ocular surface is as yet unknown.
      This case highlights that although clinically little had changed following two
      failed CLET surgeries, some subclinical improvement must have taken place for a
      DALK to remain successful after 2 years.

PMID- 23001101
TI  - Traumatic pulmonary arteriovenous fistula may be misdiagnosed with residual shunt
      after patent foramen ovale closure.
AB  - We report the case of a 48-year-old woman with a history of transient ischaemic
      attacks (TIA). The patient was diagnosed with a large patent foramen ovale (PFO),
      for which she underwent percutaneous PFO closure. Two years postprocedurally, the
      patient suffered frequent TIA and assessment showed the displacement of the
      device. The device was surgically removed, and the septum was repaired with a
      pericardial patch. Afterward, however, the patient experienced repeat TIA. It was
      discovered that the patient had a pulmonary arteriovenous fistula (PAVF), and a
      diagnosis of a trauma was made. The PAVF was later coil embolised. This case
      illustrates the importance of evaluating PFO closure patients for the associated
      causes of right-to-left shunting.

PMID- 23001102
TI  - Takotsubo cardiomyopathy as a source of cardioembolic cerebral infarction.
AB  - Takotsubo cardiomyopathy is a stress-related cardiomyopathy that mimics acute
      myocardial infarction. However, it is frequently without obstructive coronary
      artery disease and is mainly seen in postmenopausal women after an emotional or
      physiological event. In rare cases, it favours the formation of intracardiac
      mural thrombus and subsequent cardioembolic events. We report a rare case where a
      patient developed a cerebral infarction as a cardioembolic sequela of takotsubo
      cardiomyopathy following the death of her beloved dog. The patient was
      successfully managed with anticoagulation where a repeat echocardiogram 4 months
      later showed resolution of the apical thrombus along with recovery of systolic
      function and left ventricle regional wall abnormalities. This case serves to
      increase awareness about the rare cardioembolic complications of takotsubo
      cardiomyopathy and emphasise the need for serial echocardiographic examinations
      and anticoagulation.

PMID- 23001103
TI  - An uncommon presentation of ductal carcinoma in situ.
AB  - A 47-year-old woman presented with 6 weeks history of non-blood-stained nipple
      discharge. Two separate nipple cytology assessments revealed malignant cells
      despite normal clinical examination and radiological investigation (mammogram,
      ultrasound and MRI). The patient elected for a central segmentectomy which
      revealed a 1.8 cm area of high-grade comedo ductal carcinoma in situ in the
      subareolar region. The patient made a good postoperative recovery. 6 months
      follow-up revealed a 5 mm area of new calcification, core biopsy revealed
      atypical cells. After counselling, the patient elected for bilateral mastectomy
      which revealed fibrocystic tissue only.

PMID- 23001104
TI  - Giant tuberculoma in an adolescent: atypical form of tuberculosis.
AB  - A tuberculoma is a rare form of presentation of tuberculosis (TB) in children. We
      describe the case of a 13-year-old girl, with 3&emsp14;weeks of progressive
      tiredness and asthenia and a 48 h fever and cough. Physical examination revealed
      diminished pulmonary sounds in the left lower hemithorax. A chest radiograph
      showed an oval hypotransparency image in this location. The TB skin test was
      anergic and sputum was negative for acid-fast bacilli (AFB). The thoracic CT
      revealed a cystic mass in the left lower half hemithorax, compressing the
      adjacent pulmonary lobe, with double non-calcificated membrane. The exeresis of
      the pulmonary mass was performed and the anatomopathological study revealed a
      tuberculoma with AFB. TB treatment was established with a favourable clinical and
      radiological evolution. TB is a prevalent disease around the world. In this case,
      due to the mass dimensions and adjacent-organ compression, surgery was essential
      for a favourable clinical evolution.

PMID- 23001105
TI  - Dental avulsion due to direct laryngoscopy during the induction of general
      anaesthesia and avulsed teeth in nasopharynx.
AB  - General anaesthesia was induced to a 32-year-old female patient. During direct
      laryngoscopy, the four upper front incisors were avulsed and fell into the
      patient's oral cavity without fracture. After endotracheal intubation, her oral
      cavity was searched laryngoscopically but the teeth were not found. Radiological
      findings of her chest and abdomen obtained by the C-armed x-ray device and
      endoscopic findings of the oesophagus were normal. Her head and neck imaging
      revealed a radiopaque lesion in the nasopharyngeal area. Later, the
      nasopharyngeal area was examined endoscopically and the teeth were removed
      following adenoidectomy. We emphasise that preoperative evaluation is essential
      for dental injuries, and patients with a risk of dental injury must be detected
      before surgery. The localisation of the broken teeth must be identified and
      removed, and one must keep in mind that the dental fragments can travel to the
      nasopharynx.

PMID- 23001106
TI  - Congenital pseudarthrosis of clavicle: illustrated operative technique and
      histological findings.
AB  - Congenital pseudarthrosis of the clavicle is a rare condition present at birth
      but often diagnosed later in childhood. Indications for surgical treatment
      include pain, deformity or neurovascular compromise. Reconstruction usually
      involves resection of the pseudarthrosis, placement of iliac crest bone graft or
      graft substitute and internal fixation. In this paper, we present a case of
      congenital pseudarthrosis of the clavicle in a 9-year-old boy who was treated
      with plate fixation and bone autograft. The majority of patients who undergo
      surgery because of cosmetic or functional problem heal well and proceed with a
      normal, unrestricted life. However, for those patients who are not bothered by
      the cosmetic appearance of the pseudarthrosis and are asymptomatic in that they
      are not functionally limited, non-surgical treatment is a viable option.

PMID- 23001107
TI  - Cardiac tamponade as the first manifestation of systemic lupus erythematosus in
      children.
AB  - Systemic lupus erythematosus (SLE) is a serious chronic autoimmune disease with
      intense inflammatory response and damage in many target organs including joints,
      skin, kidneys, heart and nervous system. Cardiac tamponade is extremely rare as a
      cardinal presentation of SLE in children with only a few cases reported in the
      literature. We report two cases of a 9-year-old boy and an 11-year-old girl
      presenting with acute cardiac tamponade and later recognition of elevated anti
      double-stranded DNA (anti-dsDNA) titre. We also present a literature review about
      similar cases in children and we stress on the importance of screening all cases
      of acute cardiac tamponade in children with antinuclear and anti-dsDNA antibodies
      to avoid any delay in SLE diagnosis and treatment.

PMID- 23001108
TI  - Sudden onset loss of vision following subarachnoid haemorrhage.

PMID- 23001109
TI  - Bickerstaff's brainstem encephalitis associated with ulcerative colitis.
AB  - A 25-year-old Japanese man showed symptoms of common cold and digestive problems
      for 1 month. He later developed hypoesthesia ascending from the lower extremities
      and consulted the emergency outpatient department with the chief complaint of
      generalised dysesthesia. Because of a history of ulcerative colitis, his
      condition was initially treated as acute aggravation of the disease; however,
      after admission, his consciousness level gradually deteriorated. Physical
      findings showed weakened tendon reflexes, and anti-GQ1b antibodies were strongly
      positive in the cerebrospinal fluid. Therefore, the patient was diagnosed with
      Bickerstaff's brainstem encephalitis (BBE). Plasmapheresis was performed 8 times,
      resulting in an improvement of the symptoms; the patient was discharged 1 month
      later. Campylobacter infections are the main cause of BBE, and its incidence is
      high among patients with ulcerative colitis. Therefore, in cases where patients
      with ulcerative colitis develop disturbance in consciousness, BBE should be
      included in the differential diagnosis.

PMID- 23001110
TI  - Opsoclonus and lingual myoclonus due to organophosphate poisoning: images in
      clinical medicine.

PMID- 23001111
TI  - [Lifestyles and oral health in Fulani populations of Ferlo in Senegal].
AB  - BACKGROUND: The population of Ferlo consists mainly of Fulani, whose lifestyle is
      characterized by nomadism and cattle breeding. The aim of this work was to study
      their dietary, living, and hygiene habits and their oral health. METHODOLOGY:
      This cross-sectional study included 300 individuals living in Tessekere and Widou
      Thiengoli, in the heart of the Great Green Wall of Senegal. These individuals
      were selected by cluster sampling and had lived in the area for over fifteen
      years. The 1997 WHO questionnaire was used to collect data from interviews and
      clinical observations. Information was collected specifically about eating
      habits, lifestyle and hygiene, dental caries (DMF) and periodontal treatment
      needs (CPITN). The coefficients of determination and correlation were used to
      explain and identify significant associations (defined by a p-value <0.05).
      RESULTS: Milk was consumed by 96% of the population and tea by 90%;47% of the
      population smoked more than half a pack of tobacco a day, 11% drank "boulfale"
      (Cologne water of 45 degrees ), and 88.6% used toothpicks for dental hygiene.
      Tooth cleaning frequency was negatively correlated with the DMF index and CPITN,
      and consumption of milk, fruit and cigarettes were positively correlated with the
      CPITN. CONCLUSION: Dietary factors, smoking and hygiene appear to influence the
      oral health of populations in Ferlo. Prevention programs should be established,
      focusing on simple information to induce behavioral change.

PMID- 23001112
TI  - Activism and health in hard times.

PMID- 23001113
TI  - An ordered organic radical adsorbed on a Cu-doped Au(111) surface.
AB  - The tri-para-carboxylic polychlorotriphenylmethyl radical adsorption on a
      Cu/Au(111) surface has been investigated in ultra-high vacuum environment. The
      presence of copper favours the formation of metal-organic assemblies, which are
      analysed using scanning tunnelling microscopy (STM) and high resolution electron
      energy loss spectroscopy (HREELS). DFT methods indicate that the unpaired
      electron survives after adsorption, thus creating systems which could be regarded
      as potential candidates for spintronics applications.

PMID- 23001115
TI  - A simple and label-free electrochemical biosensor for DNA detection based on the
      super-sandwich assay.
AB  - The focus of this work was on designing a label-free DNA biosensor based on a
      super-sandwich assay using the electrochemical impedance spectroscopy technique.
      For this purpose, we designed a signal-up configuration whose linker probes could
      hybridize with two regions of the target DNA. In this configuration, the
      presented target DNA would effectively decrease the electron transfer, which
      would improve the sensitivity of the sensor. Ultimately, we employed gel
      electrophoresis to further confirm the formation of the proposed super-sandwich
      structure.

PMID- 23001114
TI  - Osteoporosis/osteopenia as an independent factor associated with periodontitis in
      postmenopausal women: a case-control study.
AB  - This study investigated whether osteoporosis/osteopenia has an influence on the
      progression of periodontitis in postmenopausal women. The findings highlight that
      postmenopausal women with osteoporosis/osteopenia had a greater chance of
      presenting periodontitis than those with normal bone mineral density,
      particularly among nonusers of osteoporosis medications and women with a greater
      number of remaining teeth, showing that osteoporosis/osteopenia has had an
      influence on the progression of periodontitis. INTRODUCTION: This study
      investigated whether osteoporosis/osteopenia has an influence on the progression
      of periodontitis in postmenopausal women and explored the effects of use of
      osteoporosis medication and tooth loss on this association. METHODS: This case
      control study involved 521 postmenopausal women, with minimum age of 50 years, in
      Feira de Santana, Bahia, Brazil. Sociodemographic characteristics, health
      conditions/medications, and lifestyle habits were recorded. A complete
      periodontal examination was performed and periodontitis was diagnosed. Bone
      mineral density was evaluated through lumbar spine and femoral bone densitometry,
      obtained using dual-energy X-ray absorptiometry. Logistic regression was used to
      calculate the strength of association between the occurrences of
      osteoporosis/osteopenia and periodontitis. RESULTS: Women with
      osteoporosis/osteopenia were twice as likely to present periodontitis, as were
      those with normal bone mineral density, even after adjusting for smoking, age,
      family income, and last visit to dentist (odds ratios (OR)adjusted=2.24, 95% CI
      [1.24-4.06], p=0.008). Among nonusers of osteoporosis medication
      (ORadjusted=2.51, 95% CI [1.33-4.73], p=0.004) and women with at least 10
      remaining teeth (ORadjusted=2.50 95% CI [1.18-5.27], p=0.02), the odds ratio was
      higher and statistically significant. CONCLUSIONS: These findings highlight that
      postmenopausal women with osteoporosis/osteopenia had a greater chance of
      presenting periodontitis than those with normal bone mineral density,
      particularly among nonusers of osteoporosis medications and women with a greater
      number of remaining teeth.

PMID- 23001116
TI  - Platelet-rich plasma for the treatment of lateral epicondylitis: sonographic
      assessment of tendon morphology and vascularity (pilot study).
AB  - OBJECTIVE: To investigate the efficacy of using contrast-enhanced ultrasound to
      assess the relationship of altered vascularity and tendon morphology following
      injection of platelet-rich plasma (PRP) for lateral epicondylitis. MATERIALS AND
      METHODS: This study prospectively evaluated six patients who had a baseline
      ultrasound confirming tendinosis of the common extensor tendon. Patients received
      a single 3-ml PRP injection under ultrasound guidance. Grayscale images of the
      injected elbow were obtained at baseline and were repeated at 1 and 6 months
      after injection. DEFINITY(r) contrast was also injected after by 2 sets of wrist
      extension exercises in order to obtain contrast-enhanced images of the elbow.
      Qualitative and quantitative analyses of the level of enhancement to the regions
      of interest were performed using off-line quantitative analysis software.
      RESULTS: All patients had either moderate or severe common extensor tendinosis as
      determined on clinical examination and baseline imaging. Five patients
      demonstrated improved tendon morphology using ultrasound imaging 6 months after
      PRP injection (one patient was lost to follow-up). At baseline, there was
      evidence of increased vascularity at the myotendinous junction (MT) of the common
      extensor tendon when compared to its footprint (FP). There was a trend towards no
      change in FP vascularity between baseline and 6 months (p = 0.062) and between 1
      and 6 months (p = 0.288). There was a trend for increased vascularity to the MT
      region from baseline to 6 months (p = 0.433) and from 1 to 6 months (p = 0.783).
      CONCLUSIONS: Contrast-enhanced ultrasound provides a sensitive method the display
      alterations in vascularity in the common extensor tendon of the elbow. PRP
      therapy for lateral epicondylitis can improve extensor tendon morphology.
      Corresponding increased extensor tendon FP vascularity, however, was not seen.
      There is a trend for increased vascularity at the MT up to 6 months following PRP
      injection, based on limited pilot data.

PMID- 23001117
TI  - Ultrasound of displaced ulnar collateral ligament tears of the thumb: the Stener
      lesion revisited.
AB  - PURPOSE: To retrospectively characterize the ultrasound appearance of displaced
      ulnar collateral ligament (UCL) tears that are proven at surgery, and then
      determine the accuracy of the resulting ultrasound criteria in differentiating
      displaced from non-displaced UCL tears. MATERIALS AND METHODS: After
      institutional review board approval, 26 patients were identified from the
      radiology information system over a 10-year period that had ultrasound evaluation
      of the thumb and surgically proven UCL tear. Retrospective review of the
      displaced full-thickness tears was carried out to characterize displaced tears
      and to establish ultrasound criteria for such tears. A repeat retrospective
      review 4 months later of all UCL tears applied the criteria to determine accuracy
      of ultrasound in the diagnosis of displaced full-thickness UCL tear. RESULTS: The
      26 subjects consisted of 17 displaced full-thickness UCL tears, seven non
      displaced full-thickness tears, and two partial-thickness tears at surgery.
      Retrospective ultrasound review of displaced full-thickness tears identified two
      criteria present in all cases: non-visualization of the UCL ligament and presence
      of a heterogeneous mass-like area proximal to the first metacarpophalangeal
      joint. Applying these criteria at the second retrospective review resulted in 100
      % sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy. CONCLUSIONS: The ultrasound findings of absent UCL fibers and
      presence of a heterogeneous mass-like abnormality proximal to the first
      metacarpophalangeal joint achieved 100 % accuracy in differentiating displaced
      from non-displaced full-thickness UCL tear of the thumb. Displaced full-thickness
      UCL tears most commonly were located proximal to the adductor aponeurosis.

PMID- 23001118
TI  - Three-dimensional topographical variation of femoral cartilage T2 in healthy
      volunteer knees.
AB  - OBJECTIVE: Quantitative knee cartilage T2 assessment on limited two-dimensional
      midsagittal or midcoronal planes may be insufficient to assess variations in
      normal cartilage composition. The purpose of this work was to reveal
      characteristic 3D distribution of T2 values in femoral cartilage in healthy
      volunteer knees. MATERIALS AND METHODS: Sixteen volunteers were enrolled in this
      study. One knee joint in each volunteer was imaged using a 3D fast image
      employing steady-state acquisition cycled phases (FIESTA-C) sequence for modeling
      distal femoral morphology, as well as a sagittal T2 mapping of cartilage. 3D
      distribution of cartilage T2 values was generated for the femoral condyles. At
      each medial and lateral condyle, four regions of interest (ROI) were manually
      defined based on the cartilage covered by the 3D surface model of the medial and
      lateral menisci. RESULTS: The 3D maps showed a relatively inhomogeneous
      distribution of cartilage T2 on the medial and lateral condyles. Cartilage T2
      values in the internal half of the weight-bearing zone were significantly higher
      than those in all other zones on both lateral and medial condyles. CONCLUSIONS:
      Analysis of 3D distribution of femoral cartilage T2 may be valuable in
      determining the site-specific normal range of cartilage T2 in the healthy knee
      joint.

PMID- 23001119
TI  - Propofol improves recovery of the isolated working hypertrophic heart from
      ischaemia-reperfusion.
AB  - The general anaesthetic propofol shows promise in protecting normal hearts
      against various cardiac insults, but little is known about its cardioprotective
      potential in hypertrophic hearts. This study tested the hypothesis that propofol
      at a clinically relevant dose would enhance functional recovery in hypertrophic
      hearts following ischaemia. Hypertrophic hearts from spontaneously hypertensive
      rats and hearts from their normotensive controls, Wistar Kyoto Rats, were
      equilibrated in the working mode prior to global normothermic ischaemia.
      Reperfusion commenced with 10 min in Langendorff mode, followed by 30-min working
      reperfusion. Functional performance was measured throughout the working mode,
      whilst reperfusion damage was assessed from myocardial troponin I release during
      Langendorff reperfusion. Where used, 4 MUg/ml propofol was added 10 min before
      ischaemia and was washed out 10 min into working reperfusion. An additional
      protocol investigated recovery of hearts protected by normothermic hyperkalaemic
      cardioplegic arrest. Following 20-min ischaemia, reperfusion damage was
      significantly worse in hypertrophic hearts compared to normal hearts, whilst
      addition of propofol to hypertrophic hearts significantly improved the aortic
      flow (31 +/- 5.8 vs. 11.6 +/- 2.0 ml/min, n = 6-7 +/- SE, p < 0.05). Propofol
      also conferred significant protection following 30-min ischaemia where the
      recovery of cardiac output and stroke volume was similar to that for cardioplegia
      alone. Incubation with propofol improved the NADH/NAD(+) ratio in freshly
      isolated cardiomyocytes from hypertrophic hearts, suggesting possible
      improvements in metabolic flux. These findings suggest that propofol at the
      clinically relevant dose of 4 MUg/ml is as effective as cardioplegic arrest in
      protecting hypertrophic hearts against ischaemia-reperfusion.

PMID- 23001120
TI  - The effects of asymmetric ventricular filling on left-right ventricular
      interaction in the normal rat heart.
AB  - Heart failure is characterised by ventricular dysfunction and with the potential
      for changes to ventricular volumes constraining the mechanical performance of the
      heart. The contribution of this interaction from geometric changes rather than
      fibrosis or metabolic changes is unclear. Using the constant pressure Langendorff
      perfused rat heart, the volume interaction between left ventricle (LV) and right
      ventricle (RV) was investigated. RV diastolic stiffness (P < 0.001) and developed
      pressure (P < 0.001) were significantly lower than LV. When the RV was fixed at
      the end-diastolic volume (EDV) or EDV + 50 %, both LV systolic and diastolic
      performance were unaffected with increasing LV balloon volume. However, at fixed
      LV volume, RV systolic performance was significantly decreased when LV volume
      increased to EDV + 50 % when RV volume was increased incrementally between 50 and
      300 MUl (P < 0.001). Systolic interaction in RV was noted as declining RV peak
      systolic load with increasing LV systolic pressure (P < 0.05) and diastolic
      interaction was noted for RV when LV volume was increased from EDV to EDV + 50 %
      (P < 0.05). RV diastolic wall stress was increased with increasing LV balloon
      volume (P < 0.05), but LV wall stress was unaltered at fixed RV balloon volume.
      Taken together, increasing LV volume above EDV decreased systolic performance and
      triggered ventricular constraint in the RV but the RV itself had no effect on the
      performance of the LV. These results are consistent with overload of the LV
      impairing pulmonary perfusion by direct ventricular interaction with potential
      alteration to ventilation-perfusion characteristics within the lung.

PMID- 23001122
TI  - Genome-wide association study identifies a common variant in RAD51B associated
      with male breast cancer risk.
AB  - We conducted a genome-wide association study of male breast cancer comprising 823
      cases and 2,795 controls of European ancestry, with validation in independent
      sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was
      significantly associated with male breast cancer risk (P = 3.02 * 10(-13); odds
      ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P
      = 3.87 * 10(-15); OR = 1.50).

PMID- 23001121
TI  - The transient receptor potential channel TRPA1: from gene to pathophysiology.
AB  - The Transient Receptor Potential Ankyrin 1 channel (TRPA1), is a member of the
      large TRP family of ion channels, and functions as a Ca(2+) permeable non
      selective cation channel in many different cell processes, ranging from sensory
      to homeostatic tasks. TRPA1 is highly conserved across the animal kingdom. The
      only mammalian TRPA subfamily member, TRPA1, is widely expressed in neuronal
      (e.g. sensory dorsal root and trigeminal ganglia neurons)- and in non-neuronal
      cells (e.g. epithelial cells, hair cells). It exhibits 14-19 amino-(N-)terminal
      ankyrin repeats, an unusual structural feature. The TRPA1 channel is activated by
      noxious cold (<17  degrees C) as well as by a plethora of chemical compounds that
      includes not only electrophilic compounds and oxidants that can modify, in an
      alkylative or oxidative fashion, nucleophilic cysteine residues in the channel's
      N-terminus, but also compounds that do not covalently bind to the channel
      proteins (e.g. menthol, nifedipin). Based on localization and functional
      properties, TRPA1 is considered a key player in acute and chronic (neuropathic)
      pain and inflammation. Moreover, its role in the (patho)physiology of nearly all
      organ systems is anticipated, and will be discussed along with the potential of
      TRPA1 as a drug target for the management of various pathological conditions.

PMID- 23001124
TI  - Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1
      and alter gene expression.
AB  - Genome-wide association studies (GWAS) have identified thousands of SNPs that are
      associated with human traits and diseases. But, because the vast majority of
      these SNPs are located in non-coding regions of the genome, the mechanisms by
      which they promote disease risk have remained elusive. Employing a new
      methodology that combines cistromics, epigenomics and genotype imputation, we
      annotate the non-coding regions of the genome in breast cancer cells and
      systematically identify the functional nature of SNPs associated with breast
      cancer risk. Our results show that breast cancer risk-associated SNPs are
      enriched in the cistromes of FOXA1 and ESR1 and the epigenome of histone H3
      lysine 4 monomethylation (H3K4me1) in a cancer- and cell type-specific manner.
      Furthermore, the majority of the risk-associated SNPs modulate the affinity of
      chromatin for FOXA1 at distal regulatory elements, thereby resulting in allele
      specific gene expression, which is exemplified by the effect of the rs4784227 SNP
      on the TOX3 gene within the 16q12.1 risk locus.

PMID- 23001123
TI  - Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I
      interferon signature.
AB  - Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of
      adenosine to inosine in double-stranded RNA (dsRNA) and thereby potentially alter
      the information content and structure of cellular RNAs. Notably, although the
      overwhelming majority of such editing events occur in transcripts derived from
      Alu repeat elements, the biological function of non-coding RNA editing remains
      uncertain. Here, we show that mutations in ADAR1 (also known as ADAR) cause the
      autoimmune disorder Aicardi-Goutieres syndrome (AGS). As in Adar1-null mice, the
      human disease state is associated with upregulation of interferon-stimulated
      genes, indicating a possible role for ADAR1 as a suppressor of type I interferon
      signaling. Considering recent insights derived from the study of other AGS
      related proteins, we speculate that ADAR1 may limit the cytoplasmic accumulation
      of the dsRNA generated from genomic repetitive elements.

PMID- 23001125
TI  - Recurrent somatic TET2 mutations in normal elderly individuals with clonal
      hematopoiesis.
AB  - Aging is characterized by clonal expansion of myeloid-biased hematopoietic stem
      cells and by increased risk of myeloid malignancies. Exome sequencing of three
      elderly females with clonal hematopoiesis, demonstrated by X-inactivation
      analysis, identified somatic TET2 mutations. Recurrence testing identified TET2
      mutations in 10 out of 182 individuals with X-inactivation skewing. TET2
      mutations were specific to individuals with clonal hematopoiesis without
      hematological malignancies and were associated with alterations in DNA
      methylation.

PMID- 23001127
TI  - CaReS (MACT) versus microfracture in treating symptomatic patellofemoral
      cartilage defects: a retrospective matched-pair analysis.
AB  - BACKGROUND: Treating patellofemoral articular cartilage lesions remains a
      challenging task in orthopedic surgery. Whereas microfracture and autologous
      chondrocyte implantation yield good results on femoral condyles, the therapeutic
      state of the art for treating patellofemoral lesions is yet to be determined. In
      this study, we compared the CaReS technique, which is a matrix-associated
      autologous chondrocyte implantation technique, to microfracture for treating
      patellofemoral articular cartilage lesions. METHODS: Between May 2003 and
      December 2005, 17 patients with an isolated patellofemoral cartilage defect
      (International Cartilage Repair Society III/IV) were treated with the CaReS
      technique at our department. After adjusting for inclusion and exclusion
      criteria, ten of these patients could be included in this study; ten patients
      treated with microfracture were chosen as a matched-pair group. Clinical outcome
      was evaluated 3 years after surgery by the 36-item Short Form Health Survey
      Questionnaire (SF-36), International Knee Documentation Committee (IKDC)
      subjective evaluation of the knee, Lysholm Score, and Cincinnati Modified Rating
      Scale scores. RESULTS: Patients treated with CaReS had statistically
      significantly improved IKDC, Lysholm, and Cincinnati scores 36 months after
      surgery compared with preoperatively. When comparing outcome between groups 36
      months after surgery, there was no statistically difference in IKDC, Lysholm, and
      Cincinnati scores. CONCLUSIONS: This is the first trial comparing the CaReS
      technique and microfracture for treating patellofemoral articular cartilage
      lesions, and results show that CaReS((r)) yields comparable results to
      microfracture. The small number of patients is a limiting factor of the study,
      leading to results without statistical significance. A multicentric prospective
      randomized study comparing the two procedures is desirable.

PMID- 23001126
TI  - Estimating the human mutation rate using autozygosity in a founder population.
AB  - Knowledge of the rate and pattern of new mutation is critical to the
      understanding of human disease and evolution. We used extensive autozygosity in a
      genealogically well-defined population of Hutterites to estimate the human
      sequence mutation rate over multiple generations. We sequenced whole genomes from
      5 parent-offspring trios and identified 44 segments of autozygosity. Using the
      number of meioses separating each pair of autozygous alleles and the 72 validated
      heterozygous single-nucleotide variants (SNVs) from 512 Mb of autozygous DNA, we
      obtained an SNV mutation rate of 1.20 * 10(-8) (95% confidence interval 0.89-1.43
      * 10(-8)) mutations per base pair per generation. The mutation rate for bases
      within CpG dinucleotides (9.72 * 10(-8)) was 9.5-fold that of non-CpG bases, and
      there was strong evidence (P = 2.67 * 10(-4)) for a paternal bias in the origin
      of new mutations (85% paternal). We observed a non-uniform distribution of
      heterozygous SNVs (both newly identified and known) in the autozygous segments (P
      = 0.001), which is suggestive of mutational hotspots or sites of long-range gene
      conversion.

PMID- 23001128
TI  - Arthroscopic reduction and internal fixation for displaced anterior glenoid rim
      and greater tuberosity fractures.

PMID- 23001129
TI  - Background lesions during a 24-month observation period in connexin 32-deficient
      mice.
AB  - Connexin 32 (Cx32) is a major gap junction protein in the liver. Neoplastic and
      non-neoplastic lesions were examined in Cx32-deficient (Cx32KO) mice maintained
      for 24-month, and compared with those in wild-type mice as a corresponding
      control. In neoplastic lesions, hepatocellular carcinoma increased significantly
      only in male Cx32KO mice, suggesting that Cx32 deficiency may be related to their
      pathogenesis. For females, the incidence of pituitary adenoma in the pars
      distalis of Cx32KO mice was lower than that of wild-type mice. No non-neoplastic
      lesions related to Cx32-deficiency were observed in the Cx32KO mice. In
      conclusion, these results demonstrate that the incidence of hepatocellular
      carcinoma increases only in male Cx32KO mice, presumably due to enhanced tumor
      promotion and progression signals associated with Cx32 deficiency.

PMID- 23001130
TI  - Aberrant activation of hedgehog pathway in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a very common head and neck cancer in southern
      china. Despite advances in surgical and chemotherapeutic approaches, its
      prognosis is still not promising. Hedgehog signaling pathway was reported to be
      involved in a number of cancers including head and neck. However, it remains
      unclear regarding the role of this pathway in NPC. By real-time PCR, we found
      Ptch1, Smo, and Gli-1 were expressed in all human nasopharyngeal epithelial
      tissues and cell lines. Compared with nasopharyngeal normal epithelial tissues,
      the mRNA expression level of Gli-1 was higher in carcinoma and nasopharyngitis
      (NPI) epithelial tissues. While compared with nasopharyngitis epithelia, the mRNA
      expression level of Ptch1 was lower in carcinoma epithelia and normal epithelia.
      The expressions of Smo mRNA were not significantly different among these
      epithelial tissues. Immunohistochemistry analysis revealed that the expression
      level of Gli-1 was higher in NPC than NPI. Thus, our data indicated that aberrant
      activation of hedgehog pathway in NPC. Furthermore, blocking the pathway with
      cyclopamine inhibited the proliferation of NPC epithelia cell lines. In addition,
      blockade of the pathway in three NPC cell lines with cyclopamine-induced tumor
      cell apoptosis. The transcription of hedgehog target genes also is inhibited by
      cyclopamine. These data suggested that hedgehog pathway may sustain
      nasopharyngeal tumor growth. Our data demonstrated that hedgehog signaling
      pathway was involved in NPC pathogenesis and might be a novel therapeutic target
      for NPC. 

PMID- 23001131
TI  - Transglutaminase 2 exacerbates experimental autoimmune encephalomyelitis through
      positive regulation of encephalitogenic T cell differentiation and inflammation.
AB  - The increased activity of transglutaminase 2 (TG2) in various inflammatory and
      fibrotic conditions results in the development of numerous disease processes.
      Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis, is an inflammatory and demyelinating disease of the central nervous
      system and is mediated by many inflammatory cytokines and mediators. We examined
      the role of TG2 in encephalitogenic CD4(+) T cell responses and EAE development
      using mice lacking TG2 (TG2(-/-)). TG2(-/-) mice showed decreased disease
      severity as compared with wild-type (WT) mice. Treatment with cysteamine, a TG2
      inhibitor, ameliorated disease severity in WT mice. Exacerbated disability in WT
      mice resulted from the increased infiltration of cytokine-producing CD4(+) T
      cells and sustained expression of inflammatory cytokines and mediators in the
      lesion. The increased number of IL-17- and IFN-gamma-producing cells in the
      spinal cord resulted from peripheral expansion of these cells after immunization
      with myelin-derived antigen. In vitro differentiation of WT and TG2(-/-)
      splenocytes revealed that proliferation and activation-induced cell death did not
      differ, but differentiation into IL-17- or IFN-gamma-producing cells was
      increased in WT mice. Adoptive transfer experiments revealed that pathogenic
      CD4(+) T cell differentiation and disease progression were caused by both the T
      cell-intrinsic and -extrinsic effects of TG2. This study is the first to report a
      pathogenic role for TG2 in the EAE progress and suggests that therapeutic
      targeting of TG2 may be effective against multiple sclerosis.

PMID- 23001132
TI  - A novel ruthenium(II)-cobaloxime supramolecular complex for photocatalytic H2
      evolution: synthesis, characterisation and mechanistic studies.
AB  - We report the synthesis and characterization of novel mixed-metal binuclear
      ruthenium(II)-cobalt(II) photocatalysts for hydrogen evolution in acidic
      acetonitrile. First, 2-(2'-pyridyl)benzothiazole (pbt), 1, was reacted with
      RuCl(3).xH(2)O to produce [Ru(pbt)(2)Cl(2)].0.25CH(3)COCH(3), 2, which was then
      reacted with 1,10-phenanthroline-5,6-dione (phendione), 3, in order to produce
      [Ru(pbt)(2)(phendione)](PF(6))(2).4H(2)O, 4. Compound 4 was then reacted with 4
      pyridinecarboxaldehyde in order to produce [Ru(pbt)(2)(L
      pyr)](PF(6))(2).9.5H(2)O, 5 (where L-pyr = (4-pyridine)oxazolo[4,5
      f]phenanthroline). Compound 5 was then reacted with [Co(dmgBF(2))(2)(H(2)O)(2)]
      (where dmgBF(2) = difluoroboryldimethylglyoximato) in order to produce the mixed
      metal binuclear complex, [Ru(pbt)(2)(L
      pyr)Co(dmgBF(2))(2)(H(2)O)](PF(6))(2).11H(2)O.1.5CH(3)COCH(3), 6.
      [Ru(Me(2)bpy)(2)(L-pyr)Co(dmgBF(2))(2)(OH(2))](PF(6))(2), 7 (where Me(2)bpy =
      1,10-phenanthroline, 4,4'-dimethyl-2,2'-bipyridine) and [Ru(phen)(2)(L
      pyr)Co(dmgBF(2))(2)(OH(2))](PF(6))(2), 8 were also synthesised. All complexes
      were characterized by elemental analysis, ESI MS, HRMS, UV-visible absorption,
      (11)B, (19)F, and (59)Co NMR, ESR spectroscopy, and cyclic voltammetry, where
      appropriate. Photocatalytic studies carried out in acidified acetonitrile
      demonstrated constant hydrogen generation longer than a 42 hour period as
      detected by gas chromatography. Time resolved spectroscopic measurements were
      performed on compound 6, which proved an intramolecular electron transfer from an
      excited Ru(II) metal centre to the Co(II) metal centre via the bridging L-pyr
      ligand. This resulted in the formation of a cobalt(I)-containing species that is
      essential for the production of H(2) gas in the presence of H(+) ions. A proposed
      mechanism for the generation of hydrogen is presented.

PMID- 23001134
TI  - Practice of dilatation after surgical correction in anorectal malformations.
AB  - BACKGROUND: In order to prevent stricture of the neoanus after surgical
      correction, regular dilatation is recommended. There is a lack of knowledge about
      the performance of anal dilatation and the occurrence of pain. The aim of our
      investigation was to describe the practice of dilatation and to identify possible
      risk factors for painful procedures. METHODS: Congenital Uro-Rectal Malformations
      Network is a German interdisciplinary multicenter research network. With standard
      questionnaires, physicians interviewed 243 patients and/or their parents at home,
      additional 103 patients born since 2009 were assessed through their treating
      physicians. RESULTS: In total, 88 % of the patients received dilatations.
      Treatment lasted for 7 months in median (range 1-156 months), until the age of 13
      months (range 1-171 months). In 69 % painful dilatation was reported; without a
      significant differences in age or gender. In 32 % bleeding was reported. In 30 %
      at least one dilatation was performed under general anesthesia. In 11 % some kind
      of analgesia was used. Type of fistula, dilatations lasting longer than 10 months
      and Hegar size above 15 were relevant factors for experience of pain. There were
      about 16 % postoperative strictures of the neoanus, without reported differences
      in dilatation procedures; but there was a relation to type of malformation.
      CONCLUSION: Considering the high number of painful treatments, predictors for
      painful dilatations should be further clarified through standardized
      documentation and prospective evaluation in order to improve follow-up.

PMID- 23001133
TI  - Non-genomic effect of glucocorticoids on cardiovascular system.
AB  - Glucocorticoids (GCs) are essential steroid hormones for homeostasis,
      development, metabolism, and cognition and possess anti-inflammatory and
      immunosuppressive actions. Since glucocorticoid receptor II (GR) is nearly
      ubiquitous, chronic activation or depletion of GCs leads to dysfunction of
      diverse organs, including the heart and blood vessels, resulting predominantly
      from changes in gene expression. Most studies, therefore, have focused on the
      genomic effects of GC to understand its related pathophysiological
      manifestations. The nongenomic effects of GCs clearly differ from well-known
      genomic effects, with the former responding within several minutes without the
      need for protein synthesis. There is increasing evidence that the nongenomic
      actions of GCs influence various physiological functions. To develop a GC
      mediated therapeutic target for the treatment of cardiovascular disease,
      understanding the genomic and nongenomic effects of GC on the cardiovascular
      system is needed. This article reviews our current understanding of the
      underlying mechanisms of GCs on cardiovascular diseases and stress, as well as
      how nongenomic GC signaling contributes to these conditions. We suggest that
      manipulation of GC action based on both GC and GR metabolism, mitochondrial
      impact, and the action of serum- and glucocorticoid-dependent kinase 1 may
      provide new information with which to treat cardiovascular diseases.

PMID- 23001135
TI  - Ventrally dislocated attachment of the ovarian suspensory ligament, a risk factor
      for tubal occlusion as a postoperative complication of inguinal hernia repair:
      efficacy of laparoscopic inguinal hernia repair for preventing tubal damage.
AB  - PURPOSE: Although the traditional cutdown inguinal hernia repair in children is
      well established, tubal occlusion has been reported as a complication in girls.
      The purpose was to investigate the mechanism of this complication and the
      efficacy of laparoscopic repair for preventing tubal occlusion. METHODS: Between
      October 2006 and May 2010, we performed laparoscopic hernia repair in 100 girls
      (54 with a right hernia, including 2 with an inguinal ovarian hernia, 40 with a
      left hernia, including 3 with an inguinal ovarian hernias, and 6 with bilateral
      hernias). During laparoscopic repair we examined the anatomical relationship
      between the ovary, ovarian suspensory ligament, internal inguinal ring, and round
      ligament on both sides. RESULTS: In 17 cases, 5 with an inguinal ovarian hernia
      and 12 without, the suspensory ligaments were ventrally dislocated and attached
      around the internal inguinal ring, and the ovary and fallopian tube were
      positioned near the internal inguinal ring and above the pelvic brim on the side
      of the original hernia. CONCLUSION: This ventrally dislocated attachment may
      facilitate sliding of the ovaries and tubes into the hernial sac and induce tubal
      occlusion as a postoperative complication of inguinal hernia repair. The
      laparoscopic procedure makes it easy to prevent this complication.

PMID- 23001137
TI  - Temporary umbilical loop colostomy for anorectal malformations.
AB  - Transumbilical surgical procedures have been reported to be a feasible, safe, and
      cosmetically excellent procedure for various pediatric surgical diseases.
      Umbilical loop colostomies have previously been created in patients with
      Hirschsprung's disease, but not in patients with anorectal malformations (ARMs).
      We assessed the feasibility and cosmetic results of temporal umbilical loop
      colostomy (TULC) in patients with ARMs. A circumferential skin incision was made
      at the base of the umbilical cord under general anesthesia. The skin,
      subcutaneous tissue, and fascia were cored out vertically, and the umbilical
      vessels and urachal remnant were individually ligated apart from the opening in
      the fascia. A loop colostomy was created in double-barreled fashion with a high
      chimney more than 2 cm above the level of the skin. The final size of the opening
      in the skin and fascia was modified according to the size of the bowel. The bowel
      wall was fixed separately to the peritoneum and fascia with interrupted 5-0
      absorbable sutures. The bowel was opened longitudinally and everted without
      suturing to the skin. The loop was divided 7 days postoperatively, and diversion
      of the oral bowel was completed. The colostomy was closed 2-3 months after
      posterior saggital anorectoplasty through a peristomal skin incision followed by
      end-to-end anastomosis. Final wound closure was performed in a semi-opened
      fashion to create a deep umbilicus. TULCs were successfully created in seven
      infants with rectourethral bulbar fistula or rectovestibular fistula.
      Postoperative complications included mucosal prolapse in one case. No wound
      infection or spontaneous umbilical ring narrowing was observed. Skin problems
      were minimal, and stoma care could easily be performed by attaching stoma bag.
      Healing of umbilical wounds after TULC closure was excellent. The umbilicus may
      be an alternative stoma site for temporary loop colostomy in infants with
      intermediate-type anorectal malformations, who undergo radical anorectoplasty via
      a non-abdominal approach.

PMID- 23001138
TI  - The risky cocktail: what combination effects can we expect between ecstasy and
      other amphetamines?
AB  - The recreational and illicit use of amphetaminic designer compounds, specially
      3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such
      psychostimulating drugs are frequently present as complex mixtures in 'rave'
      pills, making concomitant polysubstance use a common trend. However, the
      understanding of possible combination effects with these substances is still
      scarce. The present study was aimed at predicting the cytotoxic effects of
      mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4
      methylthioamphetamine and d-amphetamine in a human hepatoma cell line.
      Concentration-response curves for all single-mixture components were recorded by
      the MTT assay. Data obtained for individual agents were then used to compute the
      additivity expectations for mixtures of definite composition, using the
      pharmacological models of concentration addition (CA) and independent action. By
      comparing the predicted calculations with the experimentally observed effects, we
      concluded that CA accurately predicts the combination of amphetamines, which act
      together to generate additive effects over a large range of concentrations.
      Notably, we observed substantial mixture effects even when each drug was present
      at low concentrations, which individually produced unnoticeable effects.
      Nonetheless, for all tested mixtures, a small deviation from additivity was
      observed towards higher concentrations, particularly at high effect levels. A
      possible metabolic interaction, which could explain such deviation, was
      investigated, and it was observed that at higher mixture concentrations increased
      MDMA metabolism could be contributing to divergences from additivity. In
      conclusion, the present work clearly demonstrates that potentially harmful
      interactions among amphetaminic drugs are expected when these drugs are taken
      concomitantly.

PMID- 23001139
TI  - A new twist to an old tale: novel insights into the differential toxicities of
      acetaminophen and its regioisomer N-acetyl-meta-aminophenol (AMAP).

PMID- 23001136
TI  - Chromosomal and related Mendelian syndromes associated with Hirschsprung's
      disease.
AB  - Hirschsprung's disease (HSCR) is a fairly frequent cause of intestinal
      obstruction in children. It is characterized as a sex-linked heterogonous
      disorder with variable severity and incomplete penetrance giving rise to a
      variable pattern of inheritance. Although Hirschsprung's disease occurs as an
      isolated phenotype in at least 70% of cases, it is not infrequently associated
      with a number of congenital abnormalities and associated syndromes, demonstrating
      a spectrum of congenital anomalies. Certain of these syndromic phenotypes have
      been linked to distinct genetic sites, indicating underlying genetic associations
      of the disease and probable gene-gene interaction, in its pathogenesis. These
      associations with HSCR include Down's syndrome and other chromosomal anomalies,
      Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital
      Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as
      well as the MEN2 and other tumour associations. A number of other autosomal
      recessive syndromes include the Shah-Waardenburg, the Bardet-Biedl and Cartilage
      hair hypoplasia, Goldberg-Shprintzen syndromes and other syndromes related to
      cholesterol and fat metabolism among others. The genetics of Hirschsprung's
      disease are highly complex with the majority of known genetic sites relating to
      the main susceptibility pathways (RET an EDNRB). Non-syndromic non-familial,
      short-segment HSCR appears to represent a non-Mendelian condition with variable
      expression and sex-dependent penetrance. Syndromic and familial forms, on the
      other hand, have complex patterns of inheritance and being reported as autosomal
      dominant, recessive and polygenic patterns of inheritance. The phenotypic
      variability and incomplete penetrance observed in Hirschsprung's disease could
      also be explained by the involvement of modifier genes, especially in its
      syndromic forms. In this review, we look at the chromosomal and Mendelian
      associations and their underlying signalling pathways, to obtain a better
      understanding of the pathogenetic mechanisms involved in developing aganglionosis
      of the distal bowel.

PMID- 23001141
TI  - Recombinant human leptin induces growth inhibition and apoptosis in human gastric
      cancer MGC-803 cells.
AB  - The aim of this study is to investigate the effect of recombinant human leptin
      (rhLep) on the proliferation of human gastric cancer MGC-803 cells and its
      underlying mechanisms. RT-PCR was performed to identify the expression of leptin
      receptor (Ob-R). Cell proliferation was measured with MTT assay. DNA content and
      cell cycle were analyzed by flow cytometry. Apoptosis was assessed by DNA ladder
      assay and flow cytometry analysis using Annexin V-FITC/PI double staining.
      Underlying mechanisms of rhLep-induced apoptosis were evaluated by the activities
      of caspase-3, -8, -9, and cytochrome c release from mitochondria. Moreover, the
      phosphorylation of STAT3 in MGC-803 cells upon rhLep administration was detected
      by Western blot analysis. Our results demonstrated that two leptin receptors (Ob
      Ra and Ob-Rb) were expressed in MGC-803 cells. rhLep diminished the proliferation
      rate of MGC-803 cells in a time- and concentration-dependent manner and induced
      MGC-803 cell apoptosis involving in the activation of caspase-8 and caspase-3 but
      not caspase-9. In addition, rhLep failed to induce cytochrome c release from
      mitochondria and had no effect on the activation of STAT3 in MGC-803 cells.
      Therefore, from these results, we concluded that rhLep significantly inhibited
      cell proliferation via G0/G1 phase cell cycle arrest and induced apoptosis
      through the extrinsic apoptotic pathway in human gastric cancer MGC-803 cells. 

PMID- 23001142
TI  - Allelic variation in paralogs of GDP-L-galactose phosphorylase is a major
      determinant of vitamin C concentrations in apple fruit.
AB  - To identify the genetic factors underlying the regulation of fruit vitamin C (L
      ascorbic acid [AsA]) concentrations, quantitative trait loci (QTL) studies were
      carried out in an F1 progeny derived from a cross between the apple (Malus *
      domestica) cultivars Telamon and Braeburn over three years. QTL were identified
      for AsA, glutathione, total antioxidant activity in both flesh and skin tissues,
      and various quality traits, including flesh browning. Four regions on chromosomes
      10, 11, 16, and 17 contained stable fruit AsA-QTL clusters. Mapping of AsA
      metabolic genes identified colocations between orthologs of GDP-L-galactose
      phosphorylase (GGP), dehydroascorbate reductase (DHAR), and nucleobase-ascorbate
      transporter within these QTL clusters. Of particular interest are the three
      paralogs of MdGGP, which all colocated within AsA-QTL clusters. Allelic variants
      of MdGGP1 and MdGGP3 derived from the cultivar Braeburn parent were also
      consistently associated with higher fruit total AsA concentrations both within
      the mapping population (up to 10-fold) and across a range of commercial apple
      germplasm (up to 6-fold). Striking differences in the expression of the cv
      Braeburn MdGGP1 allele between fruit from high- and low-AsA genotypes clearly
      indicate a key role for MdGGP1 in the regulation of fruit AsA concentrations, and
      this MdGGP allele-specific single-nucleotide polymorphism marker represents an
      excellent candidate for directed breeding for enhanced fruit AsA concentrations.
      Interestingly, colocations were also found between MdDHAR3-3 and a stable QTL for
      browning in the cv Telamon parent, highlighting links between the redox status of
      the AsA pool and susceptibility to flesh browning.

PMID- 23001143
TI  - CPDB: cysteine protease annotation database in Leishmania species.
AB  - There has been a revival of interest in Cysteine protease for Visceral
      Leishmaniasis (VL) attributed to massive outbreaks of leishmaniasis in the
      tropical region. The cysteine protease database (CPDB) was designed to find data
      related to cysteine protease (CP) of different species of Leishmania and
      Trypanosoma brucei in a single platform. This has reflected in substantial
      increase in the submission of Leishmania genome sequences to NCBI (National
      Center for Biotechnology Information) database. The CPDB database aims to provide
      a summary of data analysis, such as physiochemical and molecular properties,
      proteolytic cleavage sites, classification into functional families using SVMProt
      and other ExPASy tools. The main aim of this database is to provide different
      protein inhibitors of cysteine protease groups that were collected from
      literature and make available their 3-D structures through JMol with JAVA
      platform. These CP inhibitors are freely downloadable and also have added links
      for functional analyses of other proteins, which is helpful for users. All this
      information in CPDB, a single platform, will prove to be of great help for
      researchers who are involved in drug discovery and analysis of other
      physiochemical and molecular properties of the protein. AVAILABILITY: the
      database is available for free at.

PMID- 23001144
TI  - Inhibition of TLR signaling by a bacterial protein containing immunoreceptor
      tyrosine-based inhibitory motifs.
AB  - The protein Tir (translocated intimin receptor) in enteric bacteria shares
      sequence similarity with the host cellular immunoreceptor tyrosine-based
      inhibition motifs (ITIMs). Despite the importance of Tir in pedestal formation,
      relatively little is known about the role of Tir and its ITIMs in the regulation
      of the host immune response. Here we demonstrate that Tir from enteropathogenic
      Escherichia coli (EPEC) interacted with the host cellular tyrosine phosphatase
      SHP-1 in an ITIM phosphorylation-dependent manner. The association of Tir with
      SHP-1 facilitated the recruitment of SHP-1 to the adaptor TRAF6 and inhibited the
      ubiquitination of TRAF6. Moreover, the ITIMs of Tir suppressed EPEC-stimulated
      expression of proinflammatory cytokines and inhibited intestinal immunity to
      infection with Citrobacter rodentium. Our findings identify a previously unknown
      mechanism by which bacterial ITIM-containing proteins can inhibit innate immune
      responses.

PMID- 23001145
TI  - The proto-oncogene MYC is required for selection in the germinal center and
      cyclic reentry.
AB  - After antigenic challenge, B cells enter the dark zone (DZ) of germinal centers
      (GCs) to proliferate and hypermutate their immunoglobulin genes. Mutants with
      greater affinity for the antigen are positively selected in the light zone (LZ)
      to either differentiate into plasma and memory cells or reenter the DZ. The
      molecular circuits that govern positive selection in the GC are not known. We
      show here that the GC reaction required biphasic regulation of expression of the
      cell-cycle regulator c-Myc that involved its transient induction during early GC
      commitment, its repression by Bcl-6 in DZ B cells and its reinduction in B cells
      selected for reentry into the DZ. Inhibition of c-Myc in vivo led to GC collapse,
      which indicated an essential role for c-Myc in GCs. Our results have implications
      for the mechanism of GC selection and the role of c-Myc in lymphomagenesis.

PMID- 23001147
TI  - Studies on acedan-based mononuclear zinc complexes toward selective fluorescent
      probes for pyrophosphate.
AB  - We have demonstrated that mononuclear Zn(II)-dipicolylamine (DPA) complexes with
      an auxiliary ligand can fluorescently discriminate pyrophosphate over ATP with as
      high selectivity as the known fast responding dinuclear bis(ZnDPA) complexes.

PMID- 23001148
TI  - An observational study of the effectiveness and safety of growth hormone
      (Humatrope((r))) treatment in Japanese children with growth hormone deficiency or
      Turner syndrome.
AB  - This study assessed the effectiveness and safety of growth hormone (GH;
      Humatrope((r))) therapy in Japanese children with GH deficiency (GHD) or Turner
      syndrome (TS) enrolled in the Genetics and Neuroendocrinology of Short Stature
      International Study (GeNeSIS).  GeNeSIS is an open-label, multinational,
      multicenter, observational study conducted in 30 countries.  In this interim
      report, there were 1129 GH treatment-naive children with GHD, with a mean
      chronological age (+/- standard deviation) of 8.75 (3.32) years, and 90 girls
      with TS, with a mean chronological age of 8.93 (3.67) years.  The mean height
      standard deviation score (SDS) increased from -2.73 (0.63) SD and -2.71 (0.63) SD
      at study entry to -2.22 (0.68) SD and -2.20 (0.60) SD after 1 year of treatment
      in the GHD and TS groups, respectively.  In both groups, mean height SDS
      increased further with each year of treatment to 4 years; however, the magnitude
      of change in height SDS declined with time.  The mean insulin-like growth factor
      I SDS increased from below the mean of the reference population at study entry to
      a level similar to (GHD group) or higher than (TS group) the mean of the
      reference population during the 4-year treatment period.  The incidence of
      serious adverse events (AEs), treatment-related AEs, and AEs related to glucose
      intolerance was low in both groups (0.1% to 3.0%).  In conclusion, GH treatment
      in Japanese children with GHD or TS resulted in increased growth over a 4-year
      treatment period with a favorable safety profile; however, the improvements in
      growth declined with time.

PMID- 23001146
TI  - The cell-cycle regulator c-Myc is essential for the formation and maintenance of
      germinal centers.
AB  - Germinal centers (GCs) are sites of intense B cell proliferation and are central
      for T cell-dependent antibody responses. However, the role of c-Myc, a key cell
      cycle regulator, in this process has been questioned. Here we identified c-Myc(+)
      B cell subpopulations in immature and mature GCs and found, by genetic ablation
      of Myc, that they had indispensable roles in the formation and maintenance of
      GCs. The identification of these functionally critical cellular subsets has
      implications for human B cell lymphomagenesis, which originates mostly from GC B
      cells and frequently involves MYC chromosomal translocations. As these
      translocations are generally dependent on transcription of the recombining
      partner loci, the c-Myc(+) GC subpopulations may be at a particularly high risk
      for malignant transformation.

PMID- 23001149
TI  - Morphological analysis of vibrational hyperspectral imaging data.
AB  - This study demonstrates the use of standard morphological image processing
      techniques to reduce the hyperspectral image data of samples, containing discrete
      particles or domains, to a single average spectrum per particle. The processing
      is automated and successful even when the particles are in contact. Focal Plane
      Array, Fourier transform infrared (FTIR) absorbance images of biological cells
      are used as an example dataset. The large number of spectra in the image
      (~40,000) can be intelligently averaged to ~100 mean spectra, approximately one
      per cell, greatly simplifying further analysis. As well as reducing the data, the
      morphological analysis provides useful information, such as the size of each
      cell, and allows every spectrum associated with each cell to be identified and
      analysed independently of the full dataset. Using these methods, combined with
      principal components analysis, consistent spectral differences are found between
      the spectra of the whole cells and a cell region approximately corresponding to
      the nucleus. These spectral differences compare well with previous IR
      measurements on whole CALU-1 cells and their isolated nuclei, but with a simpler
      sample preparation. The algorithm created to analyse the CALU-1 cells has been
      applied to a second cell line (NL20), which has a very different growth
      morphology, to demonstrate that this processing method is applicable to varied
      samples with little or no modification.

PMID- 23001150
TI  - Equilibrium, photophysical and photochemical examination of anionic
      lanthanum(III) mono- and bisporphyrins: the effects of the out-of-plane
      structure.
AB  - Lanthanum(III) ions form kinetically labile complexes with the 5,10,15,20
      tetrakis(4-sulfonatophenyl)porphyrin anion (H(2)TSPP(4-)), the compositions and
      formation constants of which significantly depend on the presence of potential
      axial ligands (at 0.01 M). Deviating from the chloride ion, acetate coordinating
      to the metal center hinders the formation of a bisporphyrin complex. In these
      lanthanum(III) complexes, the metal center, due to its large ionic radius (103.2
      pm), is located out of the ligand plane, distorting it. Accordingly, the
      absorption and fluorescence spectra of these coordination compounds display
      special properties characteristic of the so-called sitting-atop (SAT) or out-of
      plane (OOP) porphyrin complexes. Metalation significantly decreases the quantum
      yield of the fluorescence from the S(1) excited state. Quantum chemical
      calculations (DFT) confirm the considerable OOP displacement of the La(III)
      center (about 120 pm in the monoporphyrin complexes). The monoporphyrins display
      efficient fluorescence (Phi ~ 0.03), while the bisporphyrin does not emit.
      Differing from the normal (in-plane) metalloporphyrins, the excitation of these
      lanthanum(III) porphyrins leads to an irreversible ligand-to-metal charge
      transfer (LMCT) followed by the opening of the porphyrin ring, which is also
      typical of OOP complexes. Dissociation releasing free-base porphyrin can also be
      observed upon irradiation of the monoporphyrin in acetate solution, while in the
      presence of chloride ions interconversions of the mono- and bisporphyrins may
      also take place beside the irreversible photoredox reaction.

PMID- 23001152
TI  - A new shrinkage estimator for dispersion improves differential expression
      detection in RNA-seq data.
AB  - Recent developments in RNA-sequencing (RNA-seq) technology have led to a rapid
      increase in gene expression data in the form of counts. RNA-seq can be used for a
      variety of applications, however, identifying differential expression (DE)
      remains a key task in functional genomics. There have been a number of
      statistical methods for DE detection for RNA-seq data. One common feature of
      several leading methods is the use of the negative binomial (Gamma-Poisson
      mixture) model. That is, the unobserved gene expression is modeled by a gamma
      random variable and, given the expression, the sequencing read counts are modeled
      as Poisson. The distinct feature in various methods is how the variance, or
      dispersion, in the Gamma distribution is modeled and estimated. We evaluate
      several large public RNA-seq datasets and find that the estimated dispersion in
      existing methods does not adequately capture the heterogeneity of biological
      variance among samples. We present a new empirical Bayes shrinkage estimate of
      the dispersion parameters and demonstrate improved DE detection.

PMID- 23001151
TI  - Monolithic and bi-layer CAD/CAM lithium-disilicate versus metal-ceramic fixed
      dental prostheses: comparison of fracture loads and failure modes after fatigue.
AB  - OBJECTIVES: The authors analyzed the effect of fatigue on the survival rate and
      fracture load of monolithic and bi-layer CAD/CAM lithium-disilicate posterior
      three-unit fixed dental prostheses (FDPs) in comparison to the metal-ceramic gold
      standard. MATERIALS AND METHODS: The authors divided 96 human premolars and
      molars into three equal groups. Lithium-disilicate ceramic (IPS-e.max-CAD) was
      milled with the CEREC-3-system in full-anatomic FDP dimensions (monolithic: M
      LiCAD) or as framework (Bi-layer: BL-LiCAD) with subsequent hand-layer veneering.
      Metal-ceramic FDPs (MC) served as control. Single-load-to-failure tests were
      performed before and after mouth-motion fatigue. RESULTS: No fracture failures
      occurred during fatigue. Median fracture loads in [N], before and after fatigue
      were, respectively, as follows: M-LiCAD, 1,298/1,900; BL-LiCAD, 817/699; MC,
      1,966/1,818. M-LiCAD and MC FPDs revealed comparable fracture loads and were both
      significantly higher than BL-LiCAD. M-LiCAD and BL-LiCAD both failed from
      core/veneer bulk fracture within the connector area. MC failures were limited to
      ceramic veneer fractures exposing the metal core. Fatigue had no significant
      effect on any group. CONCLUSIONS: Posterior monolithic CAD/CAM fabricated lithium
      disilicate FPDs were shown to be fracture resistant with failure load results
      comparable to the metal-ceramic gold standard. Clinical investigations are needed
      to confirm these promising laboratory results. CLINICAL RELEVANCE: Monolithic
      CAD/CAM fabricated lithium-disilicate FDPs appeared to be a reliable treatment
      alternative for the posterior load-bearing area, whereas FDPs in bi-layer
      configuration were susceptible to low load fracture failure.

PMID- 23001153
TI  - Sulphur-doped porous carbon from a thiophene-based twin monomer.
AB  - Sulphur-doped carbon was synthesized using a thiophene-based twin monomer. While
      tetra(thiophene-2-ylmethoxy)-silane can be converted into sulphur containing
      nanocomposites, which lead to microporous sulphur-doped carbon, it is possible to
      produce additional mesopores by the use of templates. Thus, a variety of sulphur
      doped carbon materials with tailored pore texture are available.

PMID- 23001154
TI  - Gelatin-templated mesoporous titania for photocatalytic air treatment and
      application in metal chalcogenide nanoparticle-sensitized solar cells.
AB  - Mesoporous titania as powders and thin films on ITO were prepared using gelatin
      as an available and non-expensive pore-forming agent. The mesoporous TiO2
      manifested a much higher photocatalytic activity in the gas-phase air oxidation
      of ethanol and acetaldehyde than the commercial nanocrystalline TiO2 P25 (Degussa
      Corp.). The mesoporous ITO/TiO2 films exhibited 12-14% efficiency of photocurrent
      generation in aqueous Na2S electrolyte when illuminated by UV light. Deposition
      of CdS and PbS nanoparticles onto the surface of ITO/TiO2 further increases the
      photocurrent yields and expands the light sensitivity range of the films to 500
      520 nm (CdS) and to 650-700 nm (PbS).

PMID- 23001155
TI  - Untreated bilateral optic nerve sheath meningiomas observed for 27 years.
AB  - A 48-year-old woman noted progressive, painless visual loss in her left eye. She
      was diagnosed with bilateral optic nerve sheath meningiomas (ONSMs), extending
      across the planum sphenoidale. Radiation was offered, but the patient declined.
      She has been followed for more than 27 years with stable visual function and
      neuroimaging findings. Bilateral ONSMs, although usually described as aggressive
      in nature, may follow a stable clinical course.

PMID- 23001157
TI  - Aortic stiffness is related to left ventricular diastolic function in patients
      with diabetes mellitus type 1: assessment with MRI and speckle tracking strain
      analysis.
AB  - Diabetes mellitus type 1 (DM1) is associated with aortic stiffening and left
      ventricular (LV) diastolic dysfunction, however the relationship between aortic
      stiffness and LV diastolic dysfunction in DM1 patients is still largely unknown.
      The purpose of this study was to evaluate whether an increased aortic stiffness,
      expressed by increased aortic pulse wave velocity (PWV), is associated with
      subclinical LV diastolic dysfunction and decreased left atrial (LA) compliance as
      assessed with speckle tracking strain analysis in patients with DM1. Aortic PWV
      was assessed with cardiovascular magnetic resonance in 41 DM1 patients. Patients
      underwent echocardiography for assessment of conventional LV diastolic function
      indices and LV and LA longitudinal strain and strain rate (SR) assessed with
      speckle tracking strain analysis. LV SR during the isovolumic relaxation period
      (SRIVR) and LA strain were recorded and the E-wave velocity to SRIVR velocity
      ratio (E/SRIVR) was calculated. Independent samples t test and multivariate
      linear regression analyses were used for statistical analyses. Aortic PWV
      significantly correlated with SRIVR (beta = -0.71, p < 0.001), E/SRIVR (beta =
      0.61, p = 0.002) and LA strain (beta = -0.47, p = 0.014), but not with
      conventional echocardiographic markers of diastolic function (all p > 0.10). In
      DM1 patients, aortic stiffness is inversely associated with sensitive markers of
      LV diastolic function and decrease in LA compliance as measured with
      echocardiographic speckle tracking strain analysis.

PMID- 23001156
TI  - Direct and indirect interactions of the dopamine D3 receptor with glutamate
      pathways: implications for the treatment of schizophrenia.
AB  - This article, based on original data as well as on previously reported
      preclinical and clinical data that are reviewed, describes direct and indirect
      interactions of the D(3) receptor with N-methyl-D-aspartate receptor (NMDA)
      signaling and their functional consequences and therapeutic implications for
      schizophrenia. D(3) receptor immunoreactivity at ultrastructural level with
      electron microscopy was identified at presumably glutamatergic, asymmetric
      synapses of the medium-sized spiny neurons of the nucleus accumbens. This finding
      supports the existence of a direct interaction of the D(3) receptor with
      glutamate, in line with previously described interactions with NMDA signaling
      involving Ca(2+)/calmodulin-dependent protein kinase II at post-synaptic
      densities (Liu et al. 2009). Indirect interactions of the D(3) receptor with
      glutamate could involve a negative control exerted by the D(3) receptor on
      mesocortical dopamine neurons and the complex regulation of the glutamatergic
      pyramidal cells by dopamine in the prefrontal cortex. This could be exemplified
      here by the regulation of pyramidal cell activity in conditions of chronic NMDA
      receptor blockade with dizocilpine (MK-801). BP897, a D(3) receptor-selective
      partial agonist, reversed the dysregulation of cortical c-fos mRNA expression and
      pyramidal cell hyperexcitability, as measured by paired-pulse electrophysiology.
      At the behavioral level, blockade of the D(3) receptor, by known D(3) receptor
      antagonists or the novel D(3) receptor-selective antagonist F17141, produces
      antipsychotic-like effects in reversing hyperactivity and social interaction
      deficits induced by NMDA receptor blockade by MK-801 in mice. The glutamate-D(3)
      receptor interactions described here offer a conceptual framework for developing
      new D(3) receptor-selective drugs, which may appear as an original, efficacious,
      and safe way to potentially indirectly target glutamate in schizophrenia.

PMID- 23001158
TI  - Papillary muscle rupture: small life-threatening myocardial infarction.
AB  - We report the case of a 70 years old man admitted to our coronary care unit
      because of atrial fibrillation, non-ST-elevation myocardial infarction and
      cardiogenic shock. Emergency coronary angiography showed a 99 % stenosis of the
      circumflex coronary that was successfully treated with a bare metal stent. Atrial
      fibrillation was cardioverted to sinus rhythm. Nevertheless, no hemodynamic
      benefit was observed. Transesophageal echocardiography (TEE) showed rupture of
      the papillary muscle (PM). The patient underwent emergent mitral valve
      replacement. Surgical visualization of the mitral valve confirmed the rupture of
      the antero-lateral PM. The postoperative course was uneventful and the patient
      recovered fully. This case highlights that even small myocardial infarction may
      have dramatic clinical presentations such as PM rupture with cardiogenic shock.
      Clinical suspicion and rapid confirmation of the diagnosis by TEE are essential
      requirements for successful treatment.

PMID- 23001159
TI  - Effect of dose reduction on image quality and diagnostic performance in coronary
      computed tomography angiography.
AB  - To evaluate the effect of radiation dose reduction on image quality and
      diagnostic accuracy of coronary computed tomography (CT) angiography. Coronary CT
      angiography studies of 40 patients with (n = 20) and without (n = 20) significant
      (>=50 %) stenosis were included (26 male, 14 female, 57 +/- 11 years). In
      addition to the original clinical reconstruction (100 % dose), simulated images
      were created that correspond to 50, 25 and 12.5 % of the original dose. Image
      quality and diagnostic performance in identifying significant stenosis were
      determined. Receiver-operator-characteristics analysis was used to assess
      diagnostic accuracy at different dose levels. The identification of patients with
      significant stenosis decreased consistently at doses of 50, 25 and 12.5 of the
      regular clinical acquisition (100 %). The effect was relatively weak at 50 %
      dose, and was strong at dose levels of 25 and 12.5 %. At lower doses a steady
      increase was observed for false negative findings. The number of coronary artery
      segments that were rated as diagnostic decreased gradually with dose, this was
      most prominent for smaller segments. The area-under-the-curve (AUC) was 0.90 (p =
      0.4) at 50 % dose; accuracy decreased significantly with 25 % (AUC 0.70) and 12.5
      % dose (AUC 0.60) (p < 0.0001), with underestimation of patients having
      significant stenosis. The clinical acquisition protocol for evaluation of
      coronary artery stenosis with CT angiography represents a good balance between
      image quality and patient dose. A potential for a modest (<50 %) reduction of
      tube current might exist. However, more substantial reduction of tube current
      will reduce diagnostic performance of coronary CT angiography substantially.

PMID- 23001161
TI  - The enhanced recovery after surgery (ERAS) pathway for patients undergoing
      colorectal surgery: an update of meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: This study aimed to produce a comprehensive, up-to-date meta-analysis
      exploring the safety and efficacy of enhanced recovery programs after colorectal
      resection. METHOD: Medline, Embase, and Cochrane database searches were performed
      for relevant studies published between January 1966 and April 2012. All
      randomized controlled trials on fast track (FT) colorectal surgery were reviewed
      systematically. The main end points were short-term morbidity, length of primary
      postoperative hospital stay, length of total postoperative stay, readmission
      rate, and mortality. RESULTS: Seven randomized controlled trials with 852
      patients were included. The total length of hospital stay [mean difference (95 %
      confidence interval), -1.88 (-2.91, -0.86), p = 0.0003] and total complication
      rates [relative risk (95 % confidence interval), 0.69 (0.51, 0.93), p = 0.01]
      were significantly reduced in the enhanced recovery group. There was no
      statistically significant difference in readmission (risk ratio (RR) 0.90; 95 %
      confidence interval (CI) 0.52 to 1.53, p = 0.69) and mortality rates (RR 1.02; 95
      % CI 0.40 to 2.57, p = 0.97). CONCLUSION: Results suggested that enhanced
      recovery after surgery pathways can be able to reduce the length of stay and
      complication rates after major colorectal surgery without compromising patient
      safety. Future studies have to define the active elements in order to improve
      future fast track protocols.

PMID- 23001160
TI  - Prediction of tumor stage and lymph node involvement with dynamic contrast
      enhanced MRI after chemoradiotherapy for locally advanced rectal cancer.
AB  - PURPOSE: The usefulness of restaging by magnetic resonance imaging (MRI) after
      chemoradiotherapy (CTx/RTx) in patients with locally advanced rectal cancer has
      not yet been established, mostly due to the difficult differentiation between
      viable tumor and fibrosis. MRI with dynamic contrast-enhanced (DCE) sequences may
      be of additional value in distinguishing malignant from nonmalignant tissue. The
      aim of this study was to assess the accuracy of tumor, nodal staging, and
      circumferential resection margin (CRM) involvement by MRI with DCE sequences
      after CTx/RTx. METHODS: The accuracies were assessed by MRI on T2-weighted
      magnetic resonance (MR) images with DCE sequences in patients with locally
      advanced rectal cancer after a long course of CTx/RTx. MR images were assessed by
      two independent radiologists. RESULTS: For tumor staging and CRM involvement, MRI
      with DCE sequences had an accuracy of 45 and 60 %, respectively. The accuracy for
      nodal staging was 93 %. On MRI, malignant lymph nodes had a median diameter of 8
      mm (range, 4-18) and benign lymph nodes a median diameter of 4 mm (range, 3-11).
      A significant indicator for benign nodes was hypointensity on T2-weighted images
      (p < 0.001) and early complete arterial phase enhancement on DCE-weighted images
      (p < 0.001). A significant indicator for malignant nodes was heterogeneity on T2
      weighted images (chi (2), p < 0.000) and early incomplete arterial phase
      enhancement on DCE (p < 0.001). CONCLUSIONS: MRI with DCE is a useful tool for
      nodal staging after CTx/RTx. The addition of DCE sequences did not improve the
      accuracy of determining the tumor stage, CRM involvement, and in detecting
      complete response.

PMID- 23001162
TI  - Mimicking homeostatic proliferation in vitro generates T cells with high anti
      tumor function in non-lymphopenic hosts.
AB  - CD8(+) T cells undergoing homeostatic proliferation (HP) in a lymphopenic
      environment acquire a central memory-like phenotype (CD44(+) CD62L(+) Ly6c(+)).
      Such cells are readily functional in vitro, with a strong capacity to secrete
      IFNgamma and IL-2 and to lyse target cells upon antigen recognition. In vivo,
      these memory-like T cells display potent anti-tumor reactivity. When addressing
      whether these remarkable properties were "acquired" or dependent on sustained HP,
      we observed, for the first time, that memory-like T cells retained full anti
      tumor functions even when removed from their lymphopenic environment and
      retransferred into non-lymphopenic P14/Rag2(-/-) recipients (where HP is
      prevented). Moreover, memory-like T cells were superior to in vitro expanded
      effector T cells. We next sought to determine the conditions required to
      reproduce such a potent phenotype in vitro, in order to obtain optimal cells for
      adoptive cell transfer therapy. Assessing ex vivo lymph node cultures, dendritic
      cells, fibroblastic reticular cells, and HP-associated cytokines, we found that
      stimulation of naive T cells with anti-CD3/CD28 beads and IL-15 (IL-7 was
      dispensable) led to the generation of memory-like T cell with a similar
      phenotype. Both in vitro and in vivo memory-like T cells retained the capacity to
      efficiently control tumor growth in non-lymphopenic hosts upon adoptive cell
      transfer. A similar phenotype could be imparted to human peripheral blood
      leukocytes with comparable culture conditions. Our data reinforce the idea that
      in vitro-generated memory-like T cells could benefit adoptive cell transfer
      therapies.

PMID- 23001163
TI  - IFAH highlights barriers to innovation on medicines.

PMID- 23001164
TI  - Seasonal canine illness: cases suspected.

PMID- 23001165
TI  - FVE publishes guidance on responsible use of antimicrobials.

PMID- 23001166
TI  - Licence issued for pilot badger cull in Gloucestershire.

PMID- 23001167
TI  - Disciplinary charges adjourned after vet agrees to request removal from Register.

PMID- 23001169
TI  - Database lists tests for hereditary diseases in dogs and cats.

PMID- 23001172
TI  - Student-led consultations offered by Scottish practice.

PMID- 23001173
TI  - Klebsiella species septicaemia re-emerges in pigs in East Anglia.

PMID- 23001174
TI  - Diagnostics for Schmallenberg virus.

PMID- 23001175
TI  - Elevated suicide risks, cats and toxoplasmosis.

PMID- 23001176
TI  - Mental health research.

PMID- 23001177
TI  - Coat colour in South China bulls.

PMID- 23001178
TI  - Conformational modulation of Ant-Pro oligomers using chirality alteration of
      proline residues.
AB  - Structural modulation of Ant-Pro (anthranilic acid-proline) oligomers has been
      carried out by chirality alteration of the proline residues. The results suggest
      that the chirality altered oligomers show well-defined helical conformation
      featuring nine-membered hydrogen bonding interactions - without compromising
      conformational rigidity.

PMID- 23001179
TI  - Systematic review of laser and other light therapy for the management of oral
      mucositis in cancer patients.
AB  - BACKGROUND: The aim of this study was to review the available literature and
      define clinical practice guidelines for the use of laser and other light
      therapies for the prevention and treatment of oral mucositis. METHODS: A
      systematic review was conducted by the Mucositis Study Group of the Multinational
      Association of Supportive Care in Cancer/International Society of Oral Oncology.
      The body of evidence for each intervention, in each cancer treatment setting, was
      assigned an evidence level. Based on the evidence level, one of the following
      three guideline determinations was possible: recommendation, suggestion, and no
      guideline possible. RESULTS: A new recommendation was made for low-level laser
      (wavelength at 650 nm, power of 40 mW, and each square centimeter treated with
      the required time to a tissue energy dose of 2 J/cm(2) (2 s/point)) for the
      prevention of oral mucositis in adult patients receiving hematopoietic stem cell
      transplantation conditioned with high-dose chemotherapy, with or without total
      body irradiation. A new suggestion was made for low-level laser (wavelength
      around 632.8 nm) for the prevention of oral mucositis in patients undergoing
      radiotherapy, without concomitant chemotherapy, for head and neck cancer. No
      guideline was possible in other populations and for other light sources due to
      insufficient evidence. CONCLUSIONS: The increasing evidence in favor of low-level
      laser therapy allowed for the development of two new guidelines supporting this
      modality in the populations listed above. Evidence for other populations was also
      generally encouraging over a range of wavelengths and intensities. However,
      additional well-designed research is needed to evaluate the efficacy of laser and
      other light therapies in various cancer treatment settings.

PMID- 23001180
TI  - EB1 acetylation by P300/CBP-associated factor (PCAF) ensures accurate kinetochore
      microtubule interactions in mitosis.
AB  - In eukaryotes, microtubules are essential for cellular plasticity and dynamics.
      Here we show that P300/CBP-associated factor (PCAF), a kinetochore-associated
      acetyltransferase, acts as a negative modulator of microtubule stability through
      acetylation of EB1, a protein that controls the plus ends of microtubules. PCAF
      acetylates EB1 on K220 and disrupts the stability of a hydrophobic cavity on the
      dimerized EB1 C terminus, which was previously reported to interact with plus-end
      tracking proteins (TIPs) containing the SxIP motif. As determined with an EB1
      acetyl-K220-specific antibody, K220 acetylation is dramatically increased in
      mitosis and localized to the spindle microtubule plus ends. Surprisingly,
      persistent acetylation of EB1 delays metaphase alignment, resulting in impaired
      checkpoint silencing. Consequently, suppression of Mad2 overrides mitotic arrest
      induced by persistent EB1 acetylation. Thus, our findings identify dynamic
      acetylation of EB1 as a molecular mechanism to orchestrate accurate kinetochore
      microtubule interactions in mitosis. These results establish a previously
      uncharacterized regulatory mechanism governing localization of microtubule plus
      end tracking proteins and thereby the plasticity and dynamics of cells.

PMID- 23001181
TI  - Annotating MYC status with 89Zr-transferrin imaging.
AB  - A noninvasive technology that quantitatively measures the activity of oncogenic
      signaling pathways could have a broad impact on cancer diagnosis and treatment
      with targeted therapies. Here we describe the development of (89)Zr
      desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission
      tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71)
      with high avidity. The use of (89)Zr-transferrin produces high-contrast PET
      images that quantitatively reflect treatment-induced changes in MYC-regulated
      TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr
      transferrin imaging can detect the in situ development of prostate cancer in a
      transgenic MYC prostate cancer model, as well as in prostatic intraepithelial
      neoplasia (PIN) before histological or anatomic evidence of invasive cancer.
      These preclinical data establish (89)Zr-transferrin as a sensitive tool for
      noninvasive measurement of oncogene-driven TFRC expression in prostate and
      potentially other cancers, with prospective near-term clinical application.

PMID- 23001182
TI  - Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF
      triggered granulopoiesis.
AB  - We found that hematopoietic cell-specific Lyn substrate 1 (HCLS1 or HS1) is
      highly expressed in human myeloid cells and that stimulation with granulocyte
      colony-stimulating factor (G-CSF) leads to HCLS1 phosphorylation. HCLS1 binds the
      transcription factor lymphoid-enhancer binding factor 1 (LEF-1), transporting LEF
      1 into the nucleus upon G-CSF stimulation and inducing LEF-1 autoregulation. In
      patients with severe congenital neutropenia, inherited mutations in the gene
      encoding HCLS1-associated protein X-1 (HAX1) lead to profound defects in G-CSF
      triggered phosphorylation of HCLS1 and subsequently to reduced autoregulation and
      expression of LEF-1. Consistent with these results, HCLS1-deficient mice are
      neutropenic. In bone marrow biopsies of the majority of tested patients with
      acute myeloid leukemia, HCLS1 protein expression is substantially elevated,
      associated with high levels of G-CSF synthesis and, in some individuals, a four
      residue insertion in a proline-rich region of HCLS1 protein known to accelerate
      intracellular signaling. These data demonstrate the importance of HCLS1 in
      myelopoiesis in vitro and in vivo.

PMID- 23001183
TI  - LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway
      and a prognostic marker.
AB  - There is a pressing need to identify prognostic markers of metastatic disease and
      targets for treatment. Combining high-throughput RNA sequencing, functional
      characterization, mechanistic studies and clinical validation, we identify
      leukemia inhibitory factor receptor (LIFR) as a breast cancer metastasis
      suppressor downstream of the microRNA miR-9 and upstream of Hippo signaling.
      Restoring LIFR expression in highly malignant tumor cells suppresses metastasis
      by triggering a Hippo kinase cascade that leads to phosphorylation, cytoplasmic
      retention and functional inactivation of the transcriptional coactivator YES
      associated protein (YAP). Conversely, loss of LIFR in nonmetastatic breast cancer
      cells induces migration, invasion and metastatic colonization through activation
      of YAP. LIFR is downregulated in human breast carcinomas and inversely correlates
      with metastasis. Notably, in approximately 1,000 nonmetastatic breast tumors,
      LIFR expression status correlated with metastasis-free, recurrence-free and
      overall survival outcomes in the patients. These findings identify LIFR as a
      metastasis suppressor that functions through the Hippo-YAP pathway and has
      significant prognostic power.

PMID- 23001184
TI  - A simultaneous voltammetric temperature and humidity sensor.
AB  - We report the simultaneous measurement of temperature and humidity by analysing
      square wave voltammetric responses of two ferrocene derivatives,
      decamethylferrocene (DmFc) and 1,2-diferrocenylethylene (bisferrocene, BisFc) in
      1-(2-methoxyethyl)-1-methyl-pyrrolidinium
      tris(pentafluoroethyl)trifluorophosphate ([Moepyrr][FAP]). These two molecules
      produce three peaks in square wave voltammetry. Through study of the peak
      potentials of BisFc/BisFc(+) (vs. DmFc/DmFc(+)) and BisFc(+)/BisFc(2+) (vs.
      DmFc/DmFc(+)) over a temperature range of 298 K to 318 K and humidity range of 1%
      to 50% using square wave voltammetry, the temperature and humidity dependences of
      the relative peak potentials were investigated. A reliable method to calculate
      the humidity and temperature based on the voltammetric experiment is
      characterised and demonstrated.

PMID- 23001185
TI  - Osteoimmunological mechanisms involved in orthodontically and bacterially induced
      periodontal stress.
AB  - BACKGROUND AND OBJECTIVE: Orthodontic tooth movement is known to cause sterile
      inflammation of the periodontal ligament (PDL). It may also be accompanied by
      pathological effects of external apical root resorption, with interindividual
      differences in the incidence and extent of resorption. An involvement of
      autoimmunological mechanisms is currently under discussion. This study aimed to
      improve our understanding of similarities between the inflammatory mechanisms
      underlying the pathophysiology of periodontitis and root resorption. MATERIALS
      AND METHODS: Human PDL cells were stimulated with interleukin (IL)-1beta/IL
      17A/IFN-gamma, or left non-stimulated. Their potential for phagocytosis was then
      evaluated by incubation with dextran or E. coli or S. aureus particles, followed
      by flow cytometric and immunohistochemical analysis. Real-time polymerase chain
      reaction (PCR) was used to analyze receptor activator of NF-kappaB ligand (RANKL)
      and osteoprotegerin (OPG) expression in PDL cells. Verification was obtained in
      vivo by studying IL-17A, RANKL, and OPG expression in biopsies of inflamed
      periodontal tissues and in biopsies of rat maxillae with mechanically induced
      root resorption. Statistical analysis included Wilcoxon's rank sum test to
      analyze gene expression data and one-way ANOVA in conjunction with Tukey's post
      hoc test to analyze flow cytometric data. RESULTS: PDL cells phagocytosed foreign
      particles under both inflammatory and non-inflammatory conditions. Furthermore,
      IL-17A significantly downregulated RANKL expression while significantly
      upregulating OPG expression in PDL cells. These immunomodulatory cytokines were
      also demonstrable in both inflammatorily altered periodontal tissues and root
      resorption lacunae, while the incidence of IL-7A was strikingly variable in
      resorption areas. CONCLUSION: PDL cells were demonstrated to effect phagocytosis
      and to express immunomodulatory molecules, which proves their capability of
      participating in periodontal osteoimmunological processes. The development of
      root resorption and periodontitis appears to be governed by similar
      pathophysiological mechanisms.

PMID- 23001186
TI  - Hydration thermodynamics of pyrochlore structured oxides from TG and first
      principles calculations.
AB  - In this contribution we investigate trends in the defect chemistry and hydration
      thermodynamics of rare-earth pyrochlore structured oxides, RE(2)X(2)O(7) (RE = La
      Lu and X = Ti, Sn, Zr and Ce). First principles density functional theory (DFT)
      calculations have been performed to elucidate trends in the general defect
      chemistry and hydration enthalpy for the above-mentioned series. Further, to
      justify the use of such theoretical methods, the hydration properties of selected
      compositions were studied by means of thermogravimetric measurements. Both DFT
      calculations and TG measurements indicate that the hydration enthalpy becomes
      less exothermic with decreasing radii of RE ions within the RE(2)X(2)O(7) series
      (X = Ti, Sn, Zr and Ce), while it is less dependent on the X site ion. The
      observed hydration trends are discussed in connection with trends in the
      stability of both protons and oxygen vacancies and changes in the electronic
      density of states and bonding environment through the series. Finally, the
      findings are discussed with respect to existing correlations for other binary and
      ternary oxides.

PMID- 23001187
TI  - Brushing without brushing?--a review of the efficacy of powered toothbrushes in
      noncontact biofilm removal.
AB  - OBJECTIVES: The aim of the present review was to analyze the impact of the
      hydrodynamic effects created by powered toothbrushes on biofilm removal in vitro.
      MATERIALS AND METHODS: A MEDLINE search was performed for publications published
      by 20 May 2012; this search was complemented by a manual search. The study
      selection, data preparation, and validity assessment were conducted by two
      reviewers. RESULTS: Sixteen studies were included. The studies differed with
      respect to the methods of biofilm formation and brushing protocols. Eighteen
      different powered toothbrush models were evaluated. Toothbrushes with side-to
      side action demonstrated biofilm removal without direct bristle contact to
      biofilms ranging from 38 to 99%. Most studies found biofilm removal exceeding
      50%. Biofilm reduction using multidimensional toothbrushes was significantly
      lower than by those with the side-to-side mode. Detachment forces due to
      hydrodynamic phenomena, passing air-liquid interfaces, and acoustic energy
      transfer were suggested to cause reduction of the biofilm. CONCLUSION: Noncontact
      biofilm reduction was obtained by the hydrodynamic effects of some powered
      toothbrushes in vitro. CLINICAL RELEVANCE: Powered toothbrushes may have the
      potential to simplify self-performed oral hygiene. However, additional beneficial
      effects of higher amounts of noncontact biofilm removal in vitro have not been
      shown clinically, yet.

PMID- 23001188
TI  - Effects of early bilateral mandibular first molar extraction on condylar and
      ramal vertical asymmetry.
AB  - OBJECTIVES: This study aims to investigate the mandibular vertical asymmetry in a
      group of adult patients who had early bilateral mandibular first molar
      extractions. METHODS: Mandibular asymmetry index measurements (condylar, ramal,
      and condylar plus ramal) were made on the panoramic radiographs of a study group
      including 30 subjects (mean age, 18.22 +/- 1.30 years) and a control group of 25
      subjects (mean age, 18.24 +/- 1.17 years). Group I comprised the control group
      patients with no extractions and had excellent class I relationships, no missing
      teeth, and slight or moderate anterior crowding. Group II included patients with
      a bilateral mandibular first molar teeth extracted before the age of 12 years.
      Student's t test was used for the comparison of asymmetry index values between
      the groups. A paired t test was used to determine possible statistically
      significant differences between the sides for condylar, ramal, and condylar plus
      ramal height measurements. RESULTS: No group showed statistically significant
      side-specific differences for posterior vertical height measurements. Condylar
      asymmetry index (CAI), ramal asymmetry index, and condylar plus ramal asymmetry
      index measurements were not statistically different between the groups (p >
      0.05). CONCLUSIONS: CAI values were significantly high when compared with the 3 %
      threshold value in the both groups, but comparisons between the groups were not
      statistically significant. CLINICAL RELEVANCE: This article investigates the
      effects of early bilateral mandibular molar teeth extraction that has never been
      investigated in the literature. The present study showed that the lengths of the
      condylar, ramal, and condylar plus ramal height were less in the study group than
      in a well-matched control group of without extraction.

PMID- 23001189
TI  - Ontogenetic changes of craniofacial complex in Turner syndrome patients treated
      with growth hormone.
AB  - OBJECTIVE: The present study assessed changes of craniofacial complex in Turner
      syndrome (TS) patients treated with growth hormone (GH) during development. The
      objective was to examine the growth rate and pattern of craniofacial structures
      and to establish effects of GH on craniofacial development. MATERIALS AND
      METHODS: The study population consisted of 15 TS patients treated with GH aged 5
      18.5 years (13.3 +/- 4.4) and corresponding control group of 45 females aged 6.8
      18.7 (11.4 +/- 2.6). According to the stage of cervical vertebral maturation,
      subjects were categorized into pre-growth (5 TS and 15 controls) and growth (10
      TS and 30 controls) subgroups. The cephalometric analysis comprised angular and
      linear variables, measured on lateral cephalometric radiographs. RESULTS: The
      mandibular corpus/anterior cranial base ratio increased significantly only in
      controls during development. In growth period, ramus/corpus ratio was
      significantly larger in TS group. SNA and SNB angles were significantly smaller
      in TS growth subgroup compared to corresponding controls. Among other variables,
      no statistically significant differences were revealed. CONCLUSIONS: In TS
      patients treated with GH, growth capacities of cranial base and maxilla are
      adequate which can be attributed to GH treatment. Shape of mandible is altered
      due to decreased growth of corpus and overdeveloped ramus. Both maxillary and
      mandibular retrognathism are becoming more expressed during development. CLINICAL
      RELEVANCE: Favorable influence of GH on craniofacial complex growth rate and
      altered growth pattern revealed in this study should be considered while planning
      both orthodontic treatment and retention.

PMID- 23001190
TI  - Melatonin in the afternoons of a gradually advancing sleep schedule enhances the
      circadian rhythm phase advance.
AB  - RATIONALE: We test methods to advance (shift earlier) circadian rhythms without
      producing misalignment between rhythms and sleep. We previously tested (1) a
      gradually advancing sleep/dark schedule plus morning bright light and
      afternoon/evening melatonin and (2) the same sleep schedule with only morning
      bright light. Now we report on the same sleep schedule with only
      afternoon/evening melatonin. OBJECTIVES: This study aims to examine phase
      advances, sleepiness, and performance in response to melatonin compared to
      placebo. METHODS: Twelve adults (five female individuals) aged 20-45 years (mean
      +/- SD = 28.3 +/- 7.3 years) completed this within-subjects placebo-controlled
      counterbalanced study. The participants slept on fixed 8-h sleep schedules for
      nine days. Then, sleep/dark was advanced by 1 h/day for three consecutive days of
      treatment. The participants took 3 mg of melatonin or placebo 11 h before
      baseline sleep midpoint (the optimal time to produce phase advances) on the first
      treatment day and 1 h earlier on each subsequent day. We measured the dim light
      melatonin onset before and after treatment. The participants rated subjective
      symptoms throughout the study. They completed the Psychomotor Vigilance Task and
      rated sleepiness from 1 h before pill ingestion until bedtime on each treatment
      day. RESULTS: Melatonin produced significantly larger advances (1.3 +/- 0.7 h)
      compared to placebo (0.7 +/- 0.7 h); however, in the hours between melatonin
      ingestion and bed, melatonin caused sleepiness and performance decrements.
      CONCLUSIONS: Adding afternoon/evening melatonin to the gradually advancing sleep
      schedule increased the phase advance, but given the side effects, like
      sleepiness, it is better to use morning bright light and perhaps a lower dose of
      melatonin.

PMID- 23001191
TI  - Laparoscopic major liver resection in Korea: a multicenter study.
AB  - INTRODUCTION: We report our experience with laparoscopic major liver resection in
      Korea based on a multicenter retrospective study. MATERIALS AND METHODS: Data
      from 1,009 laparoscopic liver resections conducted from 2001 to 2011 were
      retrospectively collected. Twelve tertiary medical centers with specialized
      hepatic surgeons participated in this study. RESULTS: Among 1,009 laparoscopic
      liver resections, major liver resections were performed in 265 patients as
      treatment for hepatocellular carcinoma, metastatic tumor, intrahepatic duct
      stone, and other conditions. The most frequently performed procedure was left
      hemihepatectomy (165 patients), followed by right hemihepatectomy (53 patients).
      Pure laparoscopic procedure was performed in 190 patients including 19 robotic
      liver resections. Hand-assisted laparoscopic liver resection was performed in
      three patients and laparoscopy-assisted liver resection in 55 patients. Open
      conversion was performed in 17 patients (6.4 %). Mean operative time and
      estimated blood loss in laparoscopic major liver resection was 399.3 +/- 169.8
      min and 836.0 +/- 1223.7 ml, respectively. Intraoperative transfusion was
      required in 65 patients (24.5 %). Mean postoperative length of stay was 12.3 +/-
      7.9 days. Postoperative complications were detected in 53 patients (20.0 %), and
      in-hospital mortality occurred in two patients (0.75 %). Mean number and mean
      maximal size of resected tumors was 1.22 +/- 1.54 and 40.0 +/- 27.8 mm,
      respectively. R0 resection was achieved in 120 patients with hepatic tumor, but
      R1 resection was performed in eight patients. Mean distance of safe resection
      margin was 14.6 +/- 15.8 mm. CONCLUSIONS: Laparoscopic major liver resection has
      become a reliable option for treatment of liver disease in Korea.

PMID- 23001192
TI  - Gas embolism in laparoscopic hepatectomy: what is the optimal pneumoperitoneal
      pressure for laparoscopic major hepatectomy?
AB  - Laparoscopic hepatectomy (LH) has become popular as a surgical treatment for
      liver diseases, and numerous recent studies indicate that it is safe and has
      advantages in selected patients. Because of the magnified view offered by the
      laparoscope under pneumoperitoneal pressure, LH results in less bleeding than
      open laparotomy. However, gas embolism is an important concern that has been
      discussed in the literature, and experimental studies have shown that LH is
      associated with a high incidence of gas embolism. Major hepatectomies are done
      laparoscopically in some centers, even though the risk of gas embolism is
      believed to be higher than for minor hepatectomy due to the wide transection
      plane with dissection of major hepatic veins and long operative time. At many
      high-volume centers, LH is performed at a pneumoperitoneal pressure less than 12
      mmHg, and reports indicate that the rate of clinically severe gas embolism is
      low. However, more studies will be necessary to elucidate the optimal
      pneumoperitoneal pressure and the incidence of gas embolism during LH.

PMID- 23001193
TI  - Extrahepatic Glissonean approach for laparoscopic major liver resection (with
      video).
AB  - Although recent technological developments and improved endoscopic procedures
      have further spread the application of laparoscopic liver resection, laparoscopic
      major liver resection remains a highly specialized field because there are major
      technical difficulties, such as hilar dissection and pedicle control. The entire
      length of the primary branches of the Glissonean pedicle and the origin of the
      secondary branches are located outside the liver. In contrast, the trunks of the
      secondary branches and more peripheral branches run inside the liver. The right,
      left, anterior, or posterior Glissonean pedicle can thus be tied and divided en
      bloc extrahepatically during open anatomical liver resection. Each Glissonean
      pedicle can be easily and safely encircled and divided en bloc extrahepatically
      during laparoscopic anatomical liver resection using an Endo Retract Maxi or Endo
      Mini-Retract. This report describes a novel technique by which the extrahepatic
      Glissonean approach appears to be both feasible and safe for the performance of
      laparoscopic major liver resection.

PMID- 23001194
TI  - Cysteine-rich matricellular protein improves callus regenerate in a rabbit trauma
      model.
AB  - PURPOSE: Open fractures with severe soft-tissue trauma are predisposed to poor
      bone healing. The vital coupling between osteo- and angiogenesis is disturbed.
      Cysteine-rich protein 61 (CYR61) is an angiogenic inducer promoting
      vascularisation. However, little is known about the effect of CYR61 on the callus
      regenerate after acute musculoskeletal trauma. Therefore, our aim was to
      determine whether local administration of CYR61: (1) has an influence on callus
      formation and remodelling, (2) increases bone volume and (3) partially restores
      callus stability. METHODS: A musculoskeletal trauma was created in 20 rabbits. To
      simulate fracture-site debridement, the limb was shortened. In the test group, a
      CYR61-coated collagen matrix was locally applied around the osteotomy. After ten
      days, gradual distraction was commenced (0.5 mm/12 h) to restore the original
      length. New bone formation was evaluated histomorphometrically, radiographically
      and biomechanically. RESULTS: Osseus consolidation occured in all animals.
      Average maximum callus diameter was higher in the test group [1.39 mm; standard
      deviation (SD) = 0.078 vs 1.26 mm (SD = 0.14); p = 0.096]. In addition, bone
      volume was higher (p = 0.11) in the test group, with a mean value of 49.73 % (SD
      = 13.68) compared with 37.6 % (SD = 5.91). Torsional strength was significantly
      higher (p = 0.005) in the test group [105.43 % (SD = 31.68 %) vs. 52.57 % (SD =
      24.39)]. Instead, stiffness of the newly reconstructed callus decreased (64.21 %
      (SD = 11.52) vs. 71.30 % (SD = 32.25) (p = 0.81)). CONCLUSIONS: CYR61 positively
      influences callus regenerate after acute trauma, not only histologically and
      radiographically but also biomechanically, most probably by a CYR61-associated
      pathway.

PMID- 23001195
TI  - A safe technique of anterior column lag screw fixation in acetabular fractures.
AB  - PURPOSE: Conventional anterior column lag screw fixation in acetabular fracture
      is a difficult technique that has potential risks of vascular injury, hip joint
      penetration and excessive radiation exposure. We propose a safe technique of
      anterior column lag screw fixation (in-out-in technique) and present the outcome.
      MATERIALS AND METHODS: Twenty-seven acetabular fractures were operated through an
      iliofemoral approach, where the 'in-out-in technique' of lag screw fixation was a
      part of the surgical procedure. The technique involved insertion of a malleolar
      screw (4.5 mm) or 6.5 mm partially threaded cancellous screw from the outer side
      of the iliac wing, 0.5-1 cm posterior and inferior to the anteroinferior iliac
      spine. The screw comes out of the bone surface to re-enter into the anterior part
      of iliopectineal eminence, and finally gains purchase in the lateral part of
      superior pubic ramus. The screw fixation procedure was under direct visualization
      without resorting to an image intensifier. The average follow-up of the patients
      was at 18.6 months (range 12-36 months). RESULTS: No loss of reduction, joint
      penetration or visceral and neurovascular injury were documented. The average
      duration of surgery was 70 min and blood loss was 290 ml. All fractures were
      united after an average period of 2.8 months. Excellent to good functional
      outcome was observed in 24 patients (88 %), on evaluation with Merle D'Aubigne
      and Postel score at the latest follow-up. CONCLUSION: We conclude that the 'in
      out-in technique' is a safe and effective method of anterior column lag screw
      fixation in acetabular fractures. It provides rigid stability and minimizes
      surgical duration, radiation exposure and intra-operative complications.

PMID- 23001196
TI  - Characterization of in vivo functions of Nicotiana benthamiana RabE1.
AB  - We characterized the gene expression, subcellular localization, and in vivo
      functions of a Nicotiana benthamiana small GTPase belonging to the RabE family,
      designated NbRabE1. The NbRabE1 promoter drove strong beta-glucuronidase reporter
      expression in young tissues containing actively dividing cells and in stomata
      guard cells. GFP fusion proteins of NbRabE1 and its dominant-negative and
      constitutively active mutants were all localized to the Golgi apparatus and the
      plasma membrane but showed different affinities for membrane attachment. Virus
      induced gene silencing of NbRabE1 resulted in pleiotropic phenotypes, including
      growth arrest, premature senescence, and abnormal leaf development. At the
      cellular level, the leaves in which NbRabE1 was silenced contained abnormal
      stomata that lacked pores or contained incomplete ventral walls, suggesting that
      NbRabE1 deficiency leads to defective guard cell cytokinesis. Ectopic expression
      of the dominant-negative mutant of NbRabE1 in Arabidopsis thaliana resulted in
      retardation of shoot and root growth accompanied by defective root hair
      formation. These developmental defects are discussed in conjunction with proposed
      functions of RabE GTPases in polarized secretory vesicle trafficking.

PMID- 23001197
TI  - An enzyme activity capable of endotransglycosylation of heteroxylan
      polysaccharides is present in plant primary cell walls.
AB  - Heteroxylans in the plant cell wall have been proposed to have a role analogous
      to that of xyloglucans or heteromannans, forming growth-restraining networks by
      interlocking cellulose microfibrils. A xylan endotransglycosylase has been
      identified that can transglycosylate heteroxylan polysaccharides in the presence
      of xylan-derived oligosaccharides. High activity was detected in ripe fruit of
      papaya (Carica papaya), but activity was also found in a range of other fruits,
      imbibed seeds and rapidly growing seedlings of cereals. Xylan
      endotransglycosylase from ripe papaya fruit used a range of heteroxylans, such as
      wheat arabinoxylan, birchwood glucuronoxylan and various heteroxylans from
      dicotyledonous primary cell walls purified from tomato and papaya fruit, as donor
      molecules. As acceptor molecules, the enzyme preferentially used xylopentaitol
      over xylohexaitol or shorter-length acceptors. Xylan endotransglycosylase was
      active over a broad pH range and could perform transglycosylation reactions up to
      55  degrees C. Xylan endotransglycosylase activity was purified from ripe papaya
      fruit by ultrafiltration and cation exchange chromatography. Highest
      endotransglycosylase activity was identified in fractions that also contained
      high xylan hydrolase activity and correlated with the presence of the
      endoxylanase CpaEXY1. Recombinant CpaEXY1 protein transiently over-expressed in
      Nicotiana benthamiana leaves showed both endoxylanase and xylan
      endotransglycosylase activities in vitro, suggesting that CpaEXY1 is a single
      enzyme with dual activity in planta. Purified native CpaEXY1 showed two- to
      fourfold higher endoxylanase than endotransglycosylase activity, suggesting that
      CpaEXY1 may act primarily as a hydrolase. We propose that xylan
      endotransglycosylase activity (like xyloglucan and mannan endotransglycosylase
      activities) could be involved in remodelling or re-arrangement of heteroxylans of
      the cellulose-non-cellulosic cell wall framework.

PMID- 23001199
TI  - DQF-MT MRI of connective tissues: application to tendon and muscle.
AB  - OBJECT: The sequence combining DQF (double quantum filtering) with magnetisation
      transfer (DQF-MT) was tested as an alternative to the DQF sequence for
      characterising tendon and muscle by MR imaging. MATERIALS AND METHODS: DQF-MT
      images of tendon-muscle phantoms were obtained at 4.7 T using ultra-short time to
      echo (UTE) methods in order to alleviate the loss of SNR due to the short T2 of
      the tissues. Two different sampling schemes of the k-space, Cartesian or radial,
      were employed. In vivo images of the human ankle on a clinical 1.5 T scanner are
      also presented. Parameters providing optimal tendon signal as well as optimal
      contrast between this tissue and muscle were determined. RESULTS: Two sets of
      parameters resulting in different contrasts between the tissues were found. For
      the first set (short creation time tau = 10 MUs and magnetisation exchange time t
      LM = 100 ms), DQF-MT signals in muscle and tendon were detected, with that of the
      tendon being the larger one. For the second set (long creation time tau = 750 MUs
      and magnetisation exchange time 10 MUs < t LM < 100 ms), the DQF-MT signal was
      detected only in the tendon, and the decay of the double quantum coherence was
      slower than that observed for the first one, which allowed us to acquire DQF-MT
      MR images on a clinical 1.5 T MR scanner with minimal software interventions. In
      favourable conditions, the DQF-MT signal in the tendon could represent up to 10 %
      of the single-quantum signal. CONCLUSION: Dipolar interaction within
      macromolecules such as collagen and myosin is at the origin of the DQF-MT signal
      observed in the first parameter set. This should enable the detection of muscle
      fibrosis.

PMID- 23001198
TI  - Assessment of left atrial functional parameters using a novel dedicated analysis
      tool for real-time three-dimensional echocardiography: validation in comparison
      to magnetic resonance imaging.
AB  - Real-time three-dimensional echocardiography (RT3DE) is superior to two
      dimensional echocardiography in assessing left atrial (LA) parameters, but to
      date algorithms developed for the left ventricle were applied due to a lack of
      dedicated LA software. In addition, no data are available on RT3DE assessment of
      active atrial contraction. The aim of this study was to validate a novel RT3DE
      analysis tool specifically dedicated to evaluate the LA. Cardiac magnetic
      resonance imaging (MRI) served as standard of reference. Fifty-five patients
      scheduled for pulmonary vein isolation underwent cardiac MRI and RT3DE. On
      ultrasound image datasets, a dynamic polyhedron model of the LA was generated
      from which LA maximum and minimum volumes (LAmax and LAmin), passive atrial
      emptying fraction (LAEF), and active atrial ejection fraction (LAEFtrue) were
      derived and compared to values obtained from cardiac MRI. High intraclass
      correlations between RT3DE and MRI were found for LAmax (r = 0.94, p < 0.001),
      LAmin (r = 0.95, p < 0.001), LAEF (r = 0.92, p < 0.001), and LAEFtrue (r = 0.87,
      p < 0.001). Similarly, Bland-Altman analysis revealed narrow limits of agreement
      for LAmax (-28.6 to 14.1 ml), LAmin (-26.8 to 12.4 ml), LAEF (-11.2 to 14.9 %),
      and LAEFtrue (-10.6 to 6.8 %). LAmax, LAmin and LAEFtrue were measured
      significantly (p < 0.05) lower by RT3DE (111 +/- 38 ml vs. 118 +/- 39 ml, 73 +/-
      38 ml vs. 80 +/- 41 ml, and 23 +/- 14 % vs. 27 +/- 14 %, respectively).
      Interobserver and intraobserver RT3DE measurements correlated closely. RT3DE
      using a novel dedicated software tool is valid, accurate and reproducible for
      assessing LA dimensional and functional parameters. This study corroborates
      previous reports and extends its validity to the assessment of active LA
      contraction.

PMID- 23001200
TI  - [The role of TGF-beta-related signal transduction pathways in pathogenesis of
      epithelial-mesenchymal transition as a key element in cancer development and
      progression].
AB  - Epithelial-mesenchymal transition (EMT) is a biological process that drives
      polarized, immotile epithelial cells to undergo multiple biochemical changes to
      acquire a mesenchymal cell phenotype. The characteristic features of EMT are cell
      apolarity, loss of cellular adhesion, reduced expression of E-cadherin and
      increased migratory capacity, as well as invasiveness. EMT is a physiological
      process that is essential for normal embryonic development. Additionally,
      abnormal activation of EMT contributes to some human pathologies such as tissue
      fibrosis, cancer cell invasion and metastasis. In both situations, the basic
      molecular mechanisms are similar, but lead to different effects depending on cell
      type and biological conditions of the environment.    TGF-beta is a
      multifunctional cytokine that controls proliferation, differentiation and other
      functions in many cell types. It has been found that neoplastic development
      converts TGF-beta into an oncogenic cytokine. It activates various molecular
      processes, which are engaged in EMT initiation. All that makes TGF-beta a key
      regulator of EMT.   

PMID- 23001201
TI  - Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating
      agents and its chemoprevention .
AB  - The use of oxazaphosphorines (cyclophosphamide, ifosfamide) in the treatment of
      numerous neoplastic disorders is associated with their essential adverse effect
      in the form of hemorrhagic cystitis, which considerably limits the safety and
      efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced
      by toxic oxazaphosphorines metabolite - acrolein with subsequent
      immunocompetetive cells activation and release of many proinflammatory agents.
      However, there are some chemoprotectant agents which help reduce the HC
      exacerbation.    The article briefly discuses the mechanism of action of
      oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development
      and currently accepted chemopreventive agents, applied to the objective of
      urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals
      administration as novel bladder protective compounds accompanying
      cyclophosphamide or ifosfamide therapy was also mentioned.   

PMID- 23001202
TI  - [The potential nephrotoxicity of antiretroviral drugs].
AB  - The intensive studies carried out in many scientific laboratories and the
      efforts of numerous pharmaceutical companies have led to the development of drugs
      which are able to effectively inhibit HIV proliferation. At present, a number of
      antiretroviral agents with different mechanisms of action are available.
      Unfortunately, long-term use of antiretroviral drugs, however, does not remain
      indifferent to the patient and can cause significant side effects.    In the
      present work, the antiretroviral drugs with a nephrotoxicity potential most
      commonly used in clinical practice are described. In the review attention has
      also been focused on the nephropathy resulting from the HIV infection alone and
      the influence of genetic factors on the occurrence of pathological changes in the
      kidney.

PMID- 23001203
TI  - [The role of metalloproteinases in modification of extracellular matrix in
      invasive tumor growth, metastasis and angiogenesis].
AB  - Extracellular matrix metalloproteinases (MMPs) are a family of endopeptydases
      which recquire a zinc ion at their active site, for proteolityc activity. There
      are six members of the MMP family: matrilysins, collagenases, stromelysins,
      gelatinases, membrane MMPs and other MMPs. Activity of MMPs is regulated at the
      level of gene transcription, mRNA stability, zymogene proteolitic activation,
      inhibition of an active enzyme and MMP degradation. Tissue inhibitors of
      metalloproteinases (TIMPs) are main intracellular inhibitors of MMPs. Host cells
      can be stimulated by tumor cells to produce MMPs by secreted interleukins,
      interferons, growth factors and an extracellular matrix metalloproteinase inducer
      (EMMPRIN). MMPs are produced by tumor cells, fibroblasts, macrophages, mast
      cells, polimorphonuclear neutrophiles (PMNs) and endothelial cells (ECs). MMPs
      affect many stages of tumor development, facilitating its growth through
      promoting tumor cells proliferation, invasion and migration, new blood vessels
      formation and blocking tumor cells apoptosis. MMPs can promote tumor development
      in several ways. ECM degradation results in release of peptide growth factors.
      Growth factors linked with cell surface or binding proteins can also be liberated
      by MMPs. MMPs can indirectly regulate integrin signalling or cleave E-cadherins,
      facilitating cell migration. MMPs support metastasis inducing an epithelial to
      mesenchymal transition (EMT). MMP also support transendothelial migration. MMPs
      support angiogenesis by releasing pro-angiogenic factors and degrading ECM to
      support ECs migration. Cell surface growth factor receptors are also cleaved by
      MMPs, which results in inhibition of tumor development, so is release of anti
      angiogenic factors from ECM. 

PMID- 23001204
TI  - [Cancer stem cells].
AB  - Cancer stem cell theory gains increasingly greater significance in the world of
      medicine. Numerous findings of scientific research in vivo and in vitro indicate
      that it is the population of undifferentiated, self-renewing cells which is
      responsible for recurrence of cancer and metastasis. Similarly to normal stem
      cells, cancer stem cells (CSC) function in the environment of the other cells of
      the organism, called the niche, where they receive signals for differentiation
      and proliferation processes. Disorders in the signaling pathways between CSC and
      the niche that result from e.g. acquired oncogenic mutations may lead to
      uncontrolled proliferation of stem cells, gaining independence from the primary
      niche or settling a new microenvironment. CSC are identified on the basis of
      specific markers - membrane proteins or cell enzymes. Methods based on the
      measurement of dye fluorescence (obtaining side population, SP) or fluorescence
      of the fluorophore conjugated with a monoclonal antibody directed against the
      specific CSC marker are used for isolation. A different method obtains
      morphologically miscellaneous clones by single cell cloning: holo-, mero- and
      paraclones. Tumor forming assay in NOD/SCID mice is a standard in vivo test that
      confirms the stem character of isolated cells. However, this model may not fully
      reflect the complexity of cancer illnesses in human beings. Solving the mystery
      of oncogenesis, including the existence of cancer stem cells, is undoubtedly one
      of the priorities of contemporary medicine that should contribute to the
      improvement of cancer therapy. 

PMID- 23001205
TI  - [The immunomodulatory role of plant polyphenols].
AB  - Polyphenols, plant secondary metabolites, are present in human diet and have been
      widely used for medical and cosmetic purposes. They possess beneficial features
      such as antioxidant, immunomodulatory, anti-cancer and antibacterial activity.
      There is some evidence that these phytochemicals can improve wound healing.
      However, more and more data suggest that, under certain conditions, they can act
      in a different, often unpredictable way. Some investigations indicate that
      polyphenols, generally known as antioxidants, can exhibit pro-oxidant, and
      therefore cytotoxic, activity. Hence, the ability of phytochemicals to induce
      apoptosis of cancer cells and bacterial cell damage may be, at least partly, due
      to their prooxidant properties. Phytocompounds enter the body through the
      digestive system where they undergo metabolic processes that often change their
      chemical features. The gastrointestinal microbiome interacts with phytochemicals
      and influences their bioavailability and absorption in the gut. Except for
      biochemical changes of plant polyphenols in the host, the achievement of
      therapeutic concentration in vivo may be the main problem in the determination of
      their real efficacy. Ambiguous results of some studies demonstrate the need for
      the development of more accurate and standardized methods for the evaluation of
      polyphenols' properties. Better understanding of human body-polyphenol
      interactions is crucial for more effective use of these phytochemicals in disease
      prevention and therapy. 

PMID- 23001206
TI  - Selected atherosclerosis risk factors in youth aged 13-15 years .
AB  - INTRODUCTION: The high frequency of cases of circulatory system conditions in
      Europe and other countries around the world requires scientific research to
      define risk factors of early atherosclerotic changes. The aim of the present
      study was to define which students are at danger of developing atherosclerosis by
      means of measuring cholesterol and triglyceride levels in blood as well as
      defining the correlation between atherosclerosis risk factors and arterial blood
      pressure, physical fitness and efficiency of the subjects. MATERIAL/METHODS: The
      research covered 167 students of Public Junior High School 1 in Biala Podlaska
      aged 13-15 years. Accutrend GCT was employed to define the levels of total
      cholesterol and triglycerides in the screen test. Those students who were found
      to have increased values of biochemical parameters of capillary blood were
      subjected to additional blood tests aiming to define complete lipid profile of
      venous blood. The blood pressure in subjects was tested three times. The Moderate
      to-Vigorous Physical Activity (MVPA) test, suggested by American authors, was
      employed to define physical activity in subjects. EUROFIT was employed to define
      physical efficiency. RESULTS: Among the 167 subjects there were found 42 students
      (25.1%) whose lipid level in capillary blood proved to be increased. Full lipid
      profile tests proved that 16 students (9.6%) had increased blood lipid levels;
      those subjects constituted the risk group. Subjects in the risk group were
      characterized by lower levels of physical activity and physical efficiency
      compared to subjects with normal blood lipid level. Moreover, the frequency of
      hypertension was greater in risk group subjects compared to subjects with normal
      blood lipid levels. INFERENCES: Students diagnosed with atherosclerosis risk
      factors require observation and early prophylactics by adopting habits of healthy
      physical activity.

PMID- 23001207
TI  - Dehydroepiandrosterone sulfate, osteoprotegerin and its soluble ligand sRANKL
      and bone metabolism in girls with anorexia nervosa.
AB  - BACKGROUND: Only scarce data exist concerning the relationship between
      dehydroepiandrosterone (DHEA) and/or its sulfate form DHEAS and bone status in
      adolescents with anorexia nervosa (AN). AIM: We investigated whether a
      relationship existed between DHEAS and bone metabolism (as assessed based on
      serum osteocalcin [OC], and collagen type I cross-linked carboxy-terminal
      telopeptide [CTx]). We also aimed to establish whether the above mentioned
      relationship might be affected by osteoprotegerin (OPG) and its soluble ligand
      sRANKL. MATERIAL/METHODS: Fifty-six female patients with AN and 21 healthy female
      subjects aged 13 to 16 years participated in the study. Serum DHEAS, OC, CTx, OPG
      and sRANKL were measured by ELISA. RESULTS: Our female patients with AN
      demonstrated significant suppression of DHEAS and bone markers, an increase in
      OPG and sRANKL levels, and a reduction of the OPG/sRANKL ratio. DHEAS, CTx and
      the OPG/sRANKL ratio correlated positively with BMI. A significant positive
      correlation was also observed between DHEAS and the OPG/sRANKL ratio, OC and the
      OPG/sRANKL ratio, and CTx and sRANKL. The correlation was negative in the case of
      DHEAS and CTx, DHEAS and sRANKL, CTx and the OPG/sRANKL ratio, and sRANKL and the
      OPG/sRANKL ratio. DISCUSSION/CONCLUSIONS: DHEAS suppression in girls with
      anorexia nervosa was associated with a decrease in the levels of bone markers, an
      increase in OPG and sRANKL concentrations and a significant decrease in the
      OPG/sRANKL ratio. DHEAS suppression in girls with anorexia nervosa might have a
      harmful effect on their bone tissue, probably via a shift in the OPG/RANKL ratio
      toward a functional excess of sRANKL.

PMID- 23001208
TI  - Monoclonal antibodies in targeted therapy.
AB  - Targeted therapy is a new therapeutic method consisting in the inhibition of
      specific molecular pathways. In modern therapy, the key role is played by
      monoclonal antibodies, included in the group of biological agents. The success of
      molecularly targeted therapy is to define the proper "molecular target",
      selecting the right drug active against a specific "target" and selecting a group
      of patients who benefit from treatment. Introduction of targeted therapy resulted
      in improved results of the treatment of many serious and chronic diseases. In
      general, targeted molecular therapies have good toxicity profiles, but some
      patients are exquisitely sensitive to these drugs and can develop particular and
      severe toxicities. Patient selection and proper monitoring significantly decrease
      the risk of life-threatening adverse events. Data concerning late side effects
      are still unavailable because of the short follow-up of molecularly targeted
      therapy. Currently in the U.S. and Europe there are approximately 31 registered
      therapeutic monoclonal antibodies, while 160 are subjected to clinical trials.
      This paper presents an overview of therapeutic monoclonal antibodies currently
      used in therapy and the present state of knowledge about them. 

PMID- 23001209
TI  - Antigen presenting cells costimulatory signaling during pre-implantation
      pregnancy.
AB  - Success of pregnancy depends on many factors. Three phenomena inducing immune
      tolerance against semi-allogeneic conceptus may play a crucial role in the pre
      implantation period of pregnancy: influence of sex hormones in sex cycle,
      presence of oocyte or embryo and the presence of semen in the female reproductive
      tract. On the other hand dendritic cells are the most effective antigen
      presenting cells in regulation of immune phenomena and also are considered as
      potent participants in inducing immune tolerance in the pregnancy. They
      communicate with T cells in cell contact-dependent manner or via cytokines.
      During cell-cell contacts, costimulatory molecules play a key role and their
      expression is often dependent on cytokines milieu. Both costimulatory molecules
      and cytokines influence generation of T regulatory cells. Interactions of these
      molecules are closely related. In this paper we would like to pay attention to
      the importance of antigen presenting cells costimulatory potency in immune
      regulation during a pre-implantation period of pregnancy.

PMID- 23001210
TI  - [Perspectives of RNA interference application in the therapy of diseases
      associated with defects in alternative RNA splicing].
AB  - The primary transcript of an eukaryotic gene (pre-mRNA) is composed of coding
      regions--exons intervened by non-coding introns--which are removed in the RNA
      splicing process, leading to the formation of mature, intron-free mRNA.
      Alternative splicing of pre-mRNA is responsible for high complexity of the
      cellular proteome and expresses effective use of genetic information contained in
      genomic DNA. Alternative splicing plays important roles in the organism,
      including apoptosis regulation or development and plasticity of the nervous
      system. The main role of alternative splicing is differential, dependent on
      conditions and the cell type, splicing of mRNA, generating diverse transcripts
      from one gene, and, after the translation, different isoforms of a particular
      protein. Because of the high complexity of this mechanism, alternative splicing
      is particularly prone to errors. The perturbations resulting from mutations in
      the key sequences for splicing regulations are especially harmful. The
      pathogenesis of numerous diseases results from disturbed alternative RNA
      splicing, and those include cancers and neurodegenerative disorders. The
      treatment of these conditions is problematic due to their genetic background and
      currently RNA interference, which is a common mechanism of eukaryotic gene
      regulation, is being studied. Initial successes in the attempts of silencing the
      expression of faulty protein isoforms support the idea of using RNA interference
      in targeting disease related to disturbances in alternative splicing of RNA.

PMID- 23001211
TI  - [Qualitative research of contexts of occupational physician's advice].
AB  - OBJECTIVES: No consistent procedure has been established for advice given by
      occupational physicians concerning scope of disease, criteria of diagnosis and
      laboratory data, and basis of judgment. The aim of this study was to identify
      practice-based contexts of occupational physician's advice. METHODS: We
      interviewed 6 occupational physicians, and held focus group discussions (FGD)
      involving 19 occupational physicians, academic researchers, and clinical doctors.
      Scripts of the interview and FGD were coded to identify the contexts of
      occupational physician's advice. Additionally, to assure the generalizability of
      the proposed contexts of occupational physician's advice, we also conducted a
      survey to collect cases of advice, for which the fitness of the proposed contexts
      was confirmed. RESULTS: Four contexts of occupational physician's advice were
      identified from interviews and FGD, and an additional context was detected
      through the occupational physician's survey, namely Type 1, work potentially
      affects a worker's health; Type 2, risk management and prevention of accidents
      relating to disease; Type 3, recommendation to visit a doctor (referral); Type 4,
      communication to the head of the department/supervisor; and Type 5, fit for work
      with appropriate adjustment of work environment and/or conditions. All 48 cases
      collected could be classified into one or more of these five contexts.
      DISCUSSION: This study clarified that several contexts exist for occupational
      physician's advice in practice. The five proposed contexts reveal different
      responsibilities and judgments between occupational physician, worker, and
      employer. Understanding the contexts of occupational physician's advice is
      important for enhancing consensus-building between stakeholders.

PMID- 23001212
TI  - [Return-to-work program with a relapse-free job retention rate of 91.6% for
      workers with mental illness].
AB  - OBJECTIVE: We evaluated the relapse-free job retention rate and cost
      effectiveness of return-to-work (RTW) programs for workers with mental illness.
      METHOD: We retrospectively evaluated a group of 196 employees of a pharmaceutical
      company in Japan who had taken sick leave because of mental illness. We found
      that the old RTW program led to 142 employees returning to work and the new RTW
      program resulted in 54 employees returning to work. In the new program, we
      introduced the following improvements: evaluation of recovery and readiness to
      return to work by using the "Daily Activity Record Sheet"; planning for RTW with
      reasonable steps in 6 months; monthly interviews with an occupational health
      physician, to keep in touch with workers in the RTW process; and arranging a
      "Return-to-Work Coordination Meeting" with occupational health specialists, to
      make reasonable adjustments to a return-to-work plan. RESULTS: The median
      duration of sick leave was 60 days longer in the new program. The relapse-free
      job retention rate within 1 year was 54.2% in the old program and was increased
      to 91.6% in the new program. The old and new programs cost 65,945 yen and 300,898
      yen, respectively. The benefits of the old and new programs were 6,226,192 yen
      and 8,418,514 yen, respectively. The return on investment (ROI) was 933%.
      CONCLUSION: The new RTW program is effective at improving the relapse-free job
      retention rate of workers with mental illness.

PMID- 23001213
TI  - [Study of the relationship between incidence of sick leave due to mental health
      failure and work rules about sick leave].
AB  - OBJECTIVES: This study examined the relationships among the support system for
      return to work, work rules about sick leave, and incidence of sick leave due to
      mental health failure. METHODS: A questionnaire was distributed to 150 workplaces
      with a history of use of the occupational health promotion center of a certain
      prefecture. The questionnaire asked about the number and duration of sick leaves
      due to mental health failure, the support system for return to work, and work
      rules about sick leave. RESULTS: A significant correlation between the number of
      permanent staff and maximum period of sick leave was found (r=0.489, p<0.001), as
      well as a significant correlation between the number of permanent staff and the
      period of monetary compensation during sick leave (r=0.315, p=0.031). In
      addition, in 9 workplaces with more than 1,000 permanent staff, a significant
      correlation between the period of monetary compensation period during sick leave
      and incidence of sick leave was found (r=0.670, p=0.048), as well as a
      significant correlation between the period of monetary compensation during sick
      leave and the average length of sick leave (r=0.866, p<0.001). CONCLUSIONS: The
      results of this study suggest the possibility that monetary compensation is
      associated with the duration of sick leave due to mental health failure.
      Hereafter, to construct a support system for mental health, consideration of the
      effect of monetary compensation appears to be required.

PMID- 23001214
TI  - Management options for visual pathway compression from optic gliomas.
AB  - Optic pathway gliomas (OPGs) manifest with neuro-ophthalmic symptoms and signs;
      however, presentation can vary as their location and growth patterns are highly
      variable. An exophytic expansion of an OPG within the intracranial cavity can
      cause compression on neurological structures, warranting intervention. However,
      management guidelines are limited and the treatment itself may also cause neuro
      ophthalmic complications. Therefore, clinical decision-making must include input
      from a multidisciplinary team that includes ophthalmology, neurosurgery,
      radiation oncology and neuroradiology.

PMID- 23001215
TI  - Asymmetric catalytic [4 + 1] annulations catalyzed by quinidine: enantioselective
      synthesis of multi-functionalized isoxazoline N-oxides.
AB  - A highly regio-, chemo-, diastereo- and enantioselective organocatalytic [4 + 1]
      annulation of 2-halo-1,3-dicarbonyl compounds with Morita-Baylis-Hillman adducts
      catalyzed by commercially available, low cost quinidine for the preparation of
      synthetically unique and medicinally multi-functionalized isoxazoline N-oxides
      with three stereogenic centers including adjacent quaternary and tertiary
      stereocenters has been developed. Notably, the unexpected product ethyl 2-((tert
      butyldimethylsilyl)oxy)-2-(5,5-diacetyl-3-((methylsulfonyl)oxy)-4
      phenylisoxazolidin-3-yl)acetate (8) bearing a quaternary stereocenter and two
      tertiary stereocenters was obtained from the undocumented 5,5-diacetyl-3-(2
      ethoxy-1-hydroxy-2-oxoethyl)-4-phenyl-4,5-dihydroisoxazole 2-oxide (4ba).

PMID- 23001217
TI  - Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune
      encephalomyelitis.
AB  - The pathophysiology of cerebral cortical lesions in multiple sclerosis (MS) is
      not understood. We investigated cerebral cortex microvessels during immune
      mediated demyelination in the MS model chronic murine experimental autoimmune
      encephalomyelitis (EAE) by immunolocalization of the endothelial cell tight
      junction (TJ) integral proteins claudin-5 and occludin, a structural protein of
      caveolae, caveolin-1, and the blood-brain barrier-specific endothelial
      transporter, Glut 1. In EAE-affected mice, there were areas of extensive subpial
      demyelination and well-demarcated lesions that extended to deeper cortical
      layers. Activation of microglia and absence of perivascular inflammatory
      infiltrates were common in these areas. Microvascular endothelial cells showed
      increased expression of caveolin-1 and a coincident loss of both claudin-5 and
      occludin normal junctional staining patterns. At a very early disease stage,
      claudin-5 molecules tended to cluster and form vacuoles that were also Glut 1
      positive; the initially preserved occludin pattern became diffusely cytoplasmic
      at more advanced stages. Possible internalization of claudin-5 on TJ dismantling
      was suggested by its coexpression with the autophagosomal marker MAP1LC3A. Loss
      of TJ integrity was confirmed by fluorescein isothiocyanate-dextran experiments
      that showed leakage of the tracer into the perivascular neuropil. These
      observations indicate that, in the cerebral cortex of EAE-affected mice, there is
      a microvascular disease that differentially targets claudin-5 and occludin during
      ongoing demyelination despite only minimal inflammation.

PMID- 23001218
TI  - Correspondence regarding: a novel cerebral microangiopathy with endothelial cell
      atypia and multifocal white matter lesions: a direct mycoplasmal infection? J
      Neuropathol Exp Neurol 2007;66: 1100-17.

PMID- 23001220
TI  - Inspiring interfaces.

PMID- 23001219
TI  - Green production of polymer-supported PdNPs: application to the environmentally
      benign catalyzed synthesis of cis-3-hexen-1-ol under flow conditions.
AB  - Pd nanoparticles generated on gel type ion-exchange resins under catalytic
      conditions show high activity, selectivity and durability in partial
      hydrogenation reactions under mild conditions, thus providing a green, low-cost
      option for fine-chemicals production. The application to the continuous-flow
      synthesis of the leaf alcohol fragrance cis-3-hexen-1-ol is demonstrated.

PMID- 23001226
TI  - Nanoparticle immunotherapy: Combo combat.

PMID- 23001227
TI  - Oxide interfaces: Instrumental insights.

PMID- 23001228
TI  - Metal/molecule interfaces: Dispersion forces unveiled.

PMID- 23001229
TI  - Organic semiconductors: No more breaks for electrons.

PMID- 23001230
TI  - Mechanical properties: Overcoming old barriers.

PMID- 23001231
TI  - Crystal nucleation: Nucleus in a droplet.

PMID- 23001232
TI  - Material witness: Bringing crystals to life.

PMID- 23001233
TI  - Soft robotics: Bionic jellyfish.

PMID- 23001234
TI  - Photonics: Upconversion goes broadband.

PMID- 23001235
TI  - Glyco-beta-cyclodextrin capped quantum dots: synthesis, cytotoxicity and optical
      detection of carbohydrate-protein interactions.
AB  - Highly fluorescent water soluble glyco-quantum dots were synthesized using a
      sonochemical procedure. The synthetic approach is based on specific host-guest
      interactions between beta-cyclodextrin (beta-CD) and trioctylphosphine oxide
      (TOPO) surfactant on quantum dots. The modified QDs were analyzed by a
      combination of FT-IR, (1)H-NOESY NMR spectroscopy and by TEM. The high sugar
      density on QDs resulted in selective colloidal aggregation with ConcanavalinA
      (ConA), Galanthus nivalis lectin (GNA) and Peanut agglutinin (PNA) lectins.
      Subsequently, in vitro studies indicated that beta-CD modification of QDs enabled
      good cell viability of human hepatocellular carcinoma cell line (HepG2) cells.
      Finally, flow cytometry and confocal imaging studies revealed that betaCDgal
      capped QDs undergo preferential binding with HepG2 cells. These results clearly
      demonstrate that beta-CD capped QDs could be a promising candidate for further
      carbohydrate-based biomedical applications.

PMID- 23001236
TI  - Occurrence and low pressure ultraviolet inactivation of yeasts in real water
      sources.
AB  - Low pressure ultraviolet photolysis proved to be an efficient treatment to
      achieve inactivation of different yeast species (Candida sp., Cryptococcus
      carnescens, Metschnikowia viticola/Candida kofuensis, Rhodosporidium babjevae,
      Rhodotorula minuta, and Rhodotorula mucilaginosa) isolated from water sources
      with very different compositions. The sensitivity degree of various yeast
      isolates to UV treatment varied among different genera. Species isolated from
      surface water gained additional photoprotective resistance as a defence mechanism
      to be able to survive under constant sunlight conditions compared to the
      groundwater isolates. Yeasts were found to be more resistant to UV treatment than
      E. coli, Cryptosporidium, and Giardia.

PMID- 23001237
TI  - Risk evaluation and preimplantation genetic diagnosis in an infertile man with an
      unbalanced translocation t(10;15) resulting in a healthy baby.

PMID- 23001238
TI  - Putting early human development into the 4th dimension.

PMID- 23001239
TI  - Trends in HPV vaccine initiation among adolescent females in North Carolina, 2008
      2010.
AB  - BACKGROUND: To better target future immunization efforts, we assessed trends and
      disparities in human papillomavirus (HPV) vaccine initiation among female
      adolescents in North Carolina over 3 years. METHODS: We analyzed data from a
      stratified random sample of 1,427 parents who, between 2008 and 2010, completed
      two linked telephone surveys: the Behavioral Risk Factor Surveillance System and
      the Child Health Assessment and Monitoring Program surveys. Weighted analyses
      examined HPV vaccine initiation for girls ages 11 to 17 years. RESULTS: HPV
      vaccine initiation increased modestly over time (2008, 34%; 2009, 41%; 2010,
      44%). This upward trend was present within 11 subpopulations of girls, including
      those who lived in rural areas, were of minority (non-black/non-white) race, or
      had not recently received a preventive check-up. Looking at differences between
      groups, HPV vaccine initiation was less common among girls who attended private
      versus public school, were younger, or lacked a recent check-up. However, the
      latter difference narrowed over time. The low level of initiation among girls
      without recent check-ups increased substantially (from 11% to 41%), whereas
      initiation among girls with recent visits improved little (from 39% to 44%,
      P(interaction) = 0.007). CONCLUSIONS: Although HPV vaccine initiation improved
      among several groups typically at higher risk for cervical cancer, the lack of
      progress among girls with recent check-ups suggests that missed opportunities for
      administration have hampered broader improvements. IMPACT: Achieving widespread
      coverage of HPV vaccine will require redoubled efforts to vaccinate adolescents
      during routine care.

PMID- 23001241
TI  - Prospective study of genomic hypomethylation of leukocyte DNA and colorectal
      cancer risk.
AB  - BACKGROUND: Systematic genome-wide reductions of methylated cytosine (5-mC)
      levels have been observed in colorectal cancer tissue and are suspected to play a
      role in carcinogenesis, possibly as a consequence of inadequate folate intake.
      Reduced 5-mC levels in peripheral blood leukocytes have been associated with
      increased risk of colorectal cancer and adenoma in cross-sectional studies.
      METHODS: To minimize disease- and/or treatment-related effects, we studied
      leukocyte 5-mC levels in prospectively collected blood specimens of 370 cases and
      493 controls who were cancer-free at blood collection from the Prostate, Lung,
      Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Leukocyte 5-mC level was
      determined by a high-pressure liquid chromatography (HPLC)/tandem mass
      spectrometry method and expressed as the relative amount of methyl to total
      cytosine residues, or %5-mC. We estimated the association between colorectal
      cancer risk and %5-mC categories by computing ORs and 95% confidence intervals
      (CI) through logistic regression modeling. RESULTS: We observed no dose-dependent
      association between colorectal cancer and%5-mC categories (lowest vs. highest
      tertile: OR, 1.14; 95% CI, 0.80-1.63; P(trend) = 0.51). However, among subjects
      whose 5-mC levels were at the highest tertile, we observed an inverse association
      between natural folate intake and colorectal cancer (highest tertile of natural
      folate vs. lowest: OR, 0.35; 95% CI, 0.17-0.71; P(trend) = 0.003; P(interaction)
      = 0.003). CONCLUSIONS: This prospective investigation show no clear association
      between leukocyte 5-mC level and subsequent colorectal cancer risk but a
      suggestive risk modification between 5-mC level and natural folate intake.
      IMPACT: Adequate folate status may protect against colorectal carcinogenesis
      through mechanisms involving adequate DNA methylation in the genome.

PMID- 23001240
TI  - Iron in relation to gastric cancer in the Alpha-tocopherol, Beta-carotene Cancer
      Prevention Study.
AB  - BACKGROUND: Iron is an essential micronutrient that can have carcinogenic effects
      when at high or low concentrations. Previous studies of iron in relation to
      gastric cancer have not assessed subtype-specific relationships. We used the
      prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to
      assess whether iron metrics were associated with gastric cardia cancer (GCC) and
      gastric noncardia cancer (GNCC). METHODS: We selected 341 incident gastric cancer
      cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of
      follow-up, and 341 individually matched controls. We measured prediagnostic serum
      iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total
      iron-binding capacity (TIBC) and transferrin saturation were estimated from these
      metrics. Dietary iron exposures were estimated from a food frequency
      questionnaire. Multivariable logistic regression was used for analysis. RESULTS:
      Serum iron metrics were not associated with GCC, except for a potential "n"
      shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated
      with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and,
      possibly, transferrin saturation. TIBC appeared to share a "u"-shaped
      relationship with GNCC (global P = 0.033). Dietary iron exposures were not
      associated with either subsite. Adjustment for Helicobacter pylori and gastric
      atrophy had little effect on observed associations. CONCLUSIONS: We found little
      evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC
      was associated with an iron profile similar to that of iron deficiency. IMPACT:
      Our findings indicate that inverse associations between iron metrics and gastric
      cancer are driven by associations with GNCC. Further elucidation of potential
      mechanisms is warranted.

PMID- 23001242
TI  - Single-nucleotide polymorphisms in aldo-keto and carbonyl reductase genes are not
      associated with acute cardiotoxicity after daunorubicin chemotherapy.
AB  - BACKGROUND: Evidence suggests that interpatient variability in anthracycline
      metabolic rate may contribute to the cardiotoxicity associated with anthracycline
      based chemotherapy. Therefore, polymorphisms in the anthracycline metabolizing
      enzymes have been proposed as potential biomarkers of anthracycline-induced
      cardiotoxicity (AIC). METHODS: We have previously shown that 13 of the naturally
      occurring nonsynonymous single-nucleotide polymorphisms (nsSNP) in the aldo-keto
      reductases (AKR) and carbonyl reductases (CBR) reduce anthracycline metabolic
      rate in vitro. Here, we test these SNPs individually and jointly for association
      with daunorubicin-induced cardiotoxicity in patients with acute myeloid leukemia
      (AML). RESULTS: Five of the 13 nsSNPs exhibiting an in vitro effect on
      anthracycline metabolism were detected among the 185 patients with AML. No
      association was found between the SNPs and daunorubicin-induced cardiotoxicity in
      either individual or joint effect analyses. CONCLUSIONS: Despite the shown in
      vitro effect of nsSNPs in reductase genes on anthracycline metabolic rate, on
      their own these SNPs do not explain enough variability in cardiotoxicity to be
      useful markers of this adverse event. IMPACT: The results of this study provide
      important information for biomarker studies on side effects of anthracycline
      chemotherapy.

PMID- 23001244
TI  - Baseline vectorcardiography as a predictor of invasively determined acute
      hemodynamic response to cardiac resynchronization therapy.
AB  - AIMS: Identifying potential responders to cardiac resynchronization therapy (CRT)
      may be sometimes difficult and time consuming. Searching for a simple method, we
      chose vectorcardiography (VCG) for our study. The aim was to evaluate whether a
      VCG parameter can be used to predict invasively measured acute hemodynamic
      changes after CRT onset. METHODS AND RESULTS: Baseline VCG data were
      prospectively recorded just before initiation of CRT in a series of 126
      consecutive patients (?74 %, DCMP 60 %, ICMP 40 %, NYHA class III 100 %, QRS
      width 161 +/- 27 ms, LV-EF 25 +/- 6.5 %) prior to implantation at our specialized
      center. The time interval (TI) between the maximum vector and the end of the
      vector loop (initial description by Koglek W.) was correlated with acute
      hemodynamic change after CRT onset. Positive response to CRT was defined as an
      increase in dp/dt max >10 % or pulse pressure >5 %. According to these invasive
      hemodynamic parameters, 25 patients (20 %) were defined as non-responders. Using
      ROC analysis, the threshold value of the TI for responders was found to be 64 ms.
      TI is a predictor of acute hemodynamic response with a sensitivity of 96 %, a
      specificity of 76 %, a positive predictive value of 94 %, and a negative
      predictive value of 79 %. More non-responders are identified by TI than by using
      conventional QRS width in the 12-lead surface ECG. CONCLUSION: TI is a new method
      of evaluation based on baseline VCG analysis. It may be a useful diagnostic test
      for predicting acute hemodynamic response to CRT.

PMID- 23001246
TI  - Trying not to get burned: understanding homeowners' wildfire risk-mitigation
      behaviors.
AB  - Three causes have been identified for the spiraling cost of wildfire suppression
      in the United States: climate change, fuel accumulation from past wildfire
      suppression, and development in fire-prone areas. Because little is likely to be
      performed to halt the effects of climate on wildfire risk, and because fuel
      management budgets cannot keep pace with fuel accumulation let alone reverse it,
      changing the behaviors of existing and potential homeowners in fire-prone areas
      is the most promising approach to decreasing the cost of suppressing wildfires in
      the wildland-urban interface and increasing the odds of homes surviving wildfire
      events. Wildfire education efforts encourage homeowners to manage their property
      to decrease wildfire risk. Such programs may be more effective with a better
      understanding of the factors related to homeowners' decisions to undertake
      wildfire risk-reduction actions. In this study, we measured whether homeowners
      had implemented 12 wildfire risk-mitigation measures in 2 Colorado Front Range
      counties. We found that wildfire information received from local volunteer fire
      departments and county wildfire specialists, as well as talking with neighbors
      about wildfire, were positively associated with higher levels of mitigation.
      Firsthand experience in the form of preparing for or undertaking an evacuation
      was also associated with a higher level of mitigation. Finally, homeowners who
      perceived higher levels of wildfire risk on their property had undertaken higher
      levels of wildfire-risk mitigation on their property.

PMID- 23001245
TI  - Revisiting the time course of inter-trial feature priming in singleton search.
AB  - Current theories of the locus of inter-trial priming effects in efficient visual
      search posit an early perceptual component that reflects the short-term influence
      of a memory trace for low-level stimulus attributes. Despite the fact that this
      memory trace is hypothesized to be short term, and should therefore have a
      diminishing influence on performance over time, there has been relatively little
      study of the effect of time alone on singleton priming effects. The present
      series of experiments addresses this issue by systematically examining the effect
      of time on the priming of pop-out (PoP) effect. In Experiment 1, we show that the
      PoP effect does indeed diminish with increases in the RSI between trials, and
      does so in accord with a power-law function. In Experiment 2, we show that
      temporal discriminability of trial n - 1 from the trial that precedes it does not
      contribute to PoP effects. The results of Experiment 3 revealed two key results:
      (1) the PoP effect survives an equivalent number of intervening trials across
      very different RSI conditions; and (2) the cumulative target repetition benefit
      does depend on the RSI between trials. Together, the results favor neither a
      simple passive decay nor a strong episodic retrieval account of the PoP effect. 

PMID- 23001247
TI  - Longitudinal trends in diagnosis at child and adolescent mental health centres in
      Madrid, Spain.

PMID- 23001243
TI  - A pooled analysis of smoking and colorectal cancer: timing of exposure and
      interactions with environmental factors.
AB  - BACKGROUND: Considerable evidence suggests that cigarette smoking is associated
      with a higher risk of colorectal cancer (CRC). What is unclear, however, is the
      impact of quitting smoking on risk attenuation and whether other risk factors for
      CRC modify this association. METHODS: We conducted a pooled analysis of eight
      studies, including 6,796 CRC cases and 7,770 controls, to evaluate the
      association between cigarette smoking history and CRC risk and to investigate
      potential effect modification by other risk factors. RESULTS: Current smokers
      [OR, 1.26; 95% confidence interval (CI), 1.11-1.43] and former smokers (OR, 1.18;
      95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former
      smokers remained at higher CRC risk, relative to never smokers, for up to about
      25 years after quitting. The impact of time since quitting varied by cancer
      subsite: The excess risk due to smoking decreased immediately after quitting for
      proximal colon and rectal cancer but not until about 20 years post-quitting for
      distal colon cancer. Furthermore, we observed borderline statistically
      significant additive interactions between smoking status and body mass index
      [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to
      0.31; P = 0.06] and significant additive interaction between smoking status and
      fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04). CONCLUSION: CRC risk
      remained increased for about 25 years after quitting smoking, and the pattern of
      decline in risk varied by cancer subsite. BMI and fruit intake modified the risk
      associated with smoking. IMPACT: These results contribute to a better
      understanding of the mechanisms through which smoking impacts CRC etiology.

PMID- 23001248
TI  - Recommendations for a better patient care in daily clinical practice: a joint
      perspective of ESCAP and ECAP.

PMID- 23001249
TI  - Contrast-enhanced endoscopic ultrasonography in digestive diseases.
AB  - Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early
      1990s. The concept of the injection of carbon dioxide microbubbles into the
      hepatic artery as a contrast material (enhanced ultrasonography) led to
      "endoscopic ultrasonographic angiography". After the arrival of the first
      generation contrast agent, high-frequency (12 MHz) EUS brought about the
      enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper
      gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning
      endosonoscope with both radial and linear probes enabled the use of high-end
      ultrasound machines and depicted the enhancement of both color/power Doppler flow
      based imaging and harmonic-based imaging using second-generation contrast agents.
      Many reports have described the usefulness of the differential diagnosis of
      pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE
      EUS images was an objective method of diagnosis using the time-intensity curve
      (TIC), but it was limited to the region of interest. Recently developed Inflow
      Time MappingTM can be generated from stored clips and used to display the pattern
      of signal enhancement with time after injection, offering temporal difference of
      contrast agents and improved tumor characterization. On the other hand, three
      dimensional CE-EUS images added new information to the literature, but lacked
      positional information. Three-dimensional CE-EUS with accurate positional
      information is awaited. To date, most reports have been related to pancreatic
      lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in
      other organs: upper GI cancer diagnosis, submucosal tumors, and biliary
      disorders, and it might also provide functional information. Studies of CE-EUS in
      diseases in many other organs will increase in the near future.

PMID- 23001250
TI  - Effect of age and correlation between esophageal visceral chemosensitivity and
      mechanosensitivity in healthy Japanese subjects.
AB  - BACKGROUND: The aim of this study was to examine the impact of age on esophageal
      sensation, and to determine whether esophageal mechanosensitivity and
      chemosensitivity are correlated in healthy Japanese subjects. METHODS: To
      evaluate chemosensitivity, a catheter was inserted and placed 10 cm above the
      upper border of the lower esophageal sphincter (LES), which was determined with
      an esophageal manometric catheter. After saline had been infused into the
      esophagus at a rate of 10 mL/min for 2 min, 0.1 N hydrochloric acid, instead of
      saline-without the subjects' knowledge-was infused for 10 min at the same rate.
      The acid perfusion sensitivity score (APSS) was assessed. To evaluate
      mechanosensitivity, a barostat test was performed, with a balloon being placed 10
      cm above the upper border of the LES. The initial perception threshold (IPT),
      pain threshold (PT), and maximal pain were quantified. RESULTS: The APSS was
      significantly inversely correlated with age. IPT, PT, and mean maximal pain were
      significantly correlated with age. Body mass index, drinking, and smoking habits
      were not correlated with the esophageal perception threshold. The correlation of
      chemosensitivity and mechanosensitivity was also assessed, and the APSS was
      inversely correlated with IPT, PT, and maximal pain. CONCLUSIONS: The thresholds
      of esophageal visceral chemosensitivity and mechanosensitivity in same
      individuals were significantly correlated and both of these thresholds were
      inversely correlated with age.

PMID- 23001251
TI  - Gross pathological classification of peripheral cholangiocarcinoma determines the
      efficacy of hepatectomy.
AB  - BACKGROUND: Peripheral cholangiocarcinoma (PCC) can be grossly classified as mass
      forming (MF), periductal-infiltrating (PI), and intraductal papillary (IP) types.
      IP-PCC should be distinguished from other types of PCC because patients with IP
      PCC have a more favorable prognosis. We hypothesized that gross pathological
      classification of non-IP-PCC could determine the efficacy of hepatectomy.
      METHODS: We retrospectively reviewed 224 histologically proven PCCs (including
      172 PCCs from patients having non-IP type tumors) from patients who underwent
      hepatectomy between 1977 and 2007. Non-IP-PCCs were further classified as MF, MF
      mixed with PI (MF-PI), and PI for comparison. RESULTS: Of the 224 patients with
      PCC, 52 had IP-PCC (23.2 %), and 172 had non-IP-PCC (76.8 %). One hundred one of
      the 172 non-IP-PCC patients had a curative resection (curative resection rate
      58.7 %). The follow-up duration ranged from 1.1 to 193.1 months (median 13.4
      months). Overall survival (OS) rates for the non-IP-PCC patients at 1 and 5 years
      were 58.4 and 15.1 %, respectively. Absence of symptoms, lower alkaline
      phosphatase levels, normal carcinoembryonic antigen (CEA), and presence of MF
      type PCC independently and favorably affected OS for the non-IP-PCC patients
      following hepatectomy. Independent factors favorably predicting OS for the MF-PCC
      patients were the absence of symptoms, hepatolithiasis, normal CEA levels,
      successful curative hepatectomy, and negative lymph node metastasis, while for
      the MF-PI-PCC patients following hepatectomy, one independent factor, successful
      curative hepatectomy, favorably predicted OS. For the PI-PCC patients, the
      independent factors favorably predicting OS were normal albumin levels and
      negative lymph node metastasis. CONCLUSIONS: It is important to correctly
      differentiate between the gross pathological classifications of non-IP-PCC
      because of their distinct characteristics and outcomes following hepatectomy.
      Correct gross pathological classification is essential for further translational
      investigations.

PMID- 23001253
TI  - Efficient mesoporous silica-titania catalysts from colloidal self-assembly.
AB  - Mesoporous silica-titania materials of tunable composition and texture, which
      present a high catalytic activity in the mild oxidation of sulfur compounds, have
      been obtained by combining the spray-drying process with the colloidal self
      assembly of alpha-chitin nanorods (biopolymer acting as a template) and
      organometallic oligomers.

PMID- 23001252
TI  - Microscopic esophagitis distinguishes patients with non-erosive reflux disease
      from those with functional heartburn.
AB  - BACKGROUND: Microscopic esophagitis (ME) is common in patients with non-erosive
      reflux disease (NERD), and dilation of intercellular spaces (DIS) has been
      regarded as the potential main mechanism of symptom generation. We aimed to
      compare these histological abnormalities in healthy volunteers (HVs) and patients
      with erosive esophagitis (EE), NERD, and functional heartburn (FH). METHODS:
      Consecutive patients with heartburn prospectively underwent upper endoscopy and
      impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative
      patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid
      exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association
      probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/
      proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included.
      In each patient/control, multiple specimens (n = 5) were taken from the distal
      esophagus and histological alterations were evaluated. ME was diagnosed when the
      global histological score was >0.35. RESULTS: The prevalence of ME was higher (p
      < 0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH
      patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p < 0.0023), DIS (p
      < 0.0001), and papillae elongation (p < 0.0002) showed similar rates of
      prevalence in the above populations (p < 0.0001). ME, including each histological
      lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the
      histological abnormalities together, they permitted us to clearly differentiate
      EE and NERD from FH and HVs (p < 0.0001 and p < 0.0001, respectively).
      CONCLUSIONS: The lack of ME in the esophageal distal biopsies of FH patients
      indicates a limited role of these histological abnormalities in symptom
      generation in them. ME can be considered as an accurate and reliable diagnostic
      marker for distinguishing FH patients from GERD patients and has the potential to
      be used to guide the correct therapy.

PMID- 23001255
TI  - Measuring the benefit of 4 years of intravitreal ranibizumab treatment for
      neovascular age-related macular degeneration.
AB  - AIM: To analyse the benefit of intravitreal ranibizumab over 4 years for patients
      with neovascular age-related macular degeneration (AMD). METHODS: A retrospective
      case note review of all patients who started treatment between August 2007 and
      September 2009 in our unit, minimum follow-up 2 years, maximum 4 years. The main
      outcome measures were: numbers of patients with different levels of vision,
      changes in visual acuity, number of treatments and numbers remaining under follow
      up. RESULTS: 1086 eyes of 1017 patients received treatment. Numbers of patients
      remaining under follow-up were 892/1017 (87.71%) at 12 months, 730/1017 (71.78%)
      at 24 months, 468/730 (64.11%) at 36 months and 110/217 (50.69%) at 48 months.
      The main reasons for patients no longer being under follow-up were the
      consequences of old age or transfer of care. 50% of patients had 6/18 or better
      over 4 years. Patients received on average 5.79 +/- 2.53, 9.15 +/- 3.79, 11.22 +/
      4.92 and 13.7 +/- 7.84 injections by 12, 24, 36 and 48 months, respectively.
      CONCLUSIONS: We suggest that the numbers of patients with a particular level of
      vision may best reflect the actual benefit of AMD treatment provided by a
      service. Long-term follow-up is required as only 72/730 (10%) had been discharged
      at 36 months, half of whom had good vision of greater than 60 letters. 83% and
      65% of patients needed treatment in the third and fourth year. Follow-up may be
      for the rest of the patients' life or at some point they may no longer be well
      enough to attend.

PMID- 23001254
TI  - Memory-related hippocampal functioning in ecstasy and amphetamine users: a
      prospective fMRI study.
AB  - RATIONALE: Recreational use of ecstasy (3,4-methylenedioxymethamphetamine [MDMA])
      has been associated with memory impairments. Functional neuroimaging studies with
      cross-sectional designs reported altered memory-related hippocampal functioning
      in ecstasy-polydrug users. However, differences might be pre-existing or related
      to the concomitant use of amphetamine. OBJECTIVE: To prospectively investigate
      the specific effects of ecstasy on memory-related hippocampal functioning.
      METHODS: We used an associative memory task and functional magnetic resonance
      imaging (fMRI) in 40 ecstasy and/or amphetamine users at baseline (t1) and after
      12 months (t2). At t1, all subjects had very limited amphetamine and/or ecstasy
      experience (less than 5 units lifetime dose). Based on the reported drug use at
      t2, subjects with continued ecstasy and/or amphetamine use (n = 17) were compared
      to subjects who stopped use after t1 (n = 12). RESULTS: Analysis of repeated
      measures revealed that encoding-related activity in the left parahippocampal
      gyrus changed differentially between the groups. Activity in this region
      increased in abstinent subjects from t1 to t2, however, decreased in subjects
      with continued use. Decreases within the left parahippocampal gyrus were
      associated with the use of ecstasy, but not amphetamine, during the follow-up
      period. However, there were no significant differences in memory performance.
      CONCLUSIONS: The current findings suggest specific effects of ecstasy use on
      memory-related hippocampal functioning. However, alternative explanations such as
      (sub-)acute cannabis effects are conceivable.

PMID- 23001256
TI  - Intravitreal injections using a novel conjunctival mould: a comparison with a
      conventional technique.
AB  - AIMS: The aims were to compare a novel conjunctival mould used to assist the
      delivery of intravitreal drugs to a conventional technique with respect to
      patient, surgeon and cost benefit. METHODS: A prospective review of 200
      intravitreal injections was undertaken, 100 using a 'conventional' freehand
      technique (group 1) and 100 using a novel conjunctival mould (group 2).
      Intraoperative visual analogue scale (VAS) pain scores, patient preference,
      surgeon perception of the ease of insertion of the conjunctival mould were
      recorded as well as a cost comparison. RESULTS: VAS pain score in the
      conventional group was 2.58 compared to 1.38 in the conjunctival mould group
      (p<0.01). The surgeon reported the insertion of the conjunctival mould as easy in
      89 cases, moderate in 10 cases, and difficult in one case. The cost saving with a
      conjunctival mould pack compared to a conventional pack was L7.70; an annual
      saving of L19,250 for the trust. CONCLUSIONS: The reduction in the VAS pain score
      with the conjunctival mould was statistically significant (p<0.01). The surgeons
      found that the device, which was easy to insert, offered excellent globe
      stability and a safe, reproducible entry site and angle of needle insertion.

PMID- 23001257
TI  - Prevalence and predictors of Sjogren's syndrome in a prospective cohort of
      patients with aqueous-deficient dry eye.
AB  - AIMS: To assess the prevalence and determine predictors of Sjogren's syndrome
      (SS) in patients with clinically significant aqueous-deficient dry eye. METHODS:
      Patients enrolled in an industry-sponsored, multicentre clinical trial
      (NCT00784719) were assessed prospectively for the presence of SS. Ocular testing
      included Schirmer test, corneal fluorescein staining, conjunctival lissamine
      green staining, and tear-film breakup time. Review of systems questionnaire,
      medical history, dry eye questionnaire and laboratory work-up (Sjogren-specific
      antibody A (SSA), Sjogren-specific antibody B (SSB), rheumatoid factor (RF) and
      antinuclear antibody (ANA)) were obtained. RESULTS: Of 327 patients, 38 (11.6%)
      had SS: 21 (6.4%) with primary SS (pSS), and 17 (5.2%) with secondary SS. Nine
      patients (3%) were newly diagnosed using the applied diagnostic criteria based on
      American-European consensus criteria. Patients with SS had significantly worse
      conjunctival and corneal staining, Schirmer test (with and without anaesthesia),
      and symptoms compared with patients without SS. pSS Was significantly more likely
      to occur in patients with positive ANA (OR: 13.9) and RF (OR: 4.8). CONCLUSIONS:
      Ophthalmologists caring for patients with clinically significant dry eye should
      have a high index of suspicion for underlying SS and low threshold for
      serological work-up. RF and ANA are recommended as useful tests in SSA/SSB
      negative patients for further diagnostic referral.

PMID- 23001258
TI  - Sensitive detection of enantiomeric excess in different acids through chiral
      induction in an oligo(p-phenylenevinylene) aggregate.
AB  - Induction of chirality in achiral aggregates of an oligo(p-phenylenevinylene) has
      been used to detect the enantiomeric excess in acids used in the resolution of
      chiral compounds. The chiral acids which induce helicity in the aggregates are
      present at only 10% of the concentration of the chromophore, whose chiroptical
      activity can be detected using circular dichroism spectroscopy. An ee of 10% in
      mixtures of (+) and (-) acids has been clearly evidenced in a series of samples
      using only 1.5 MUg and concentration of approximately 10 MUM of the chiral
      compound. The composition of both carboxylic and phosphoric acid derivatives can
      be detected, thanks to their binding to the dimerised core ureidotriazine unit
      attached at one end of the oligo(p-phenylenevinylene) which induces a preferred
      twist in the aggregated aromatic rod. This chiral arrangement is reflected in the
      Cotton effects that the assemblies show. The sign of the induced dichroic signal
      can be affected by the substituents around a stereogenic centre of otherwise
      identical configuration, and can lead to ambidextrous assemblies as seen in
      Cotton effects at different positions for different acids. While this technique
      can be used to detect enantiomeric excess, screening of the pure enantiomers is
      wise prior to the use of the method to detect scalemic mixtures. This
      supramolecular approach to evaluation of chiral content in samples could also be
      applied to other types of aggregates based on achiral molecules which show
      sensitivity to molecular chiral inducers.

PMID- 23001259
TI  - Inkjet-printed paper-based SERS dipsticks and swabs for trace chemical detection.
AB  - We demonstrate a paper-based surface swab and lateral-flow dipstick that includes
      an inkjet-printed surface-enhanced Raman spectroscopy (SERS) substrate for
      analyte detection. Due to capillary-action wicking of cellulose, the paper
      dipstick enables extremely simple and pump-free loading of liquid samples into
      the detection device, and in addition provides inherent analyte concentration
      within the detection volume. Furthermore, the flexible nature of the paper-based
      SERS device also enables it to act as a swab to collect analyte molecules
      directly from a large-area surface; the collected analyte molecules can then be
      focused into a small-volume SERS-active region by lateral-flow concentration.
      These capabilities are unseen in today's SERS substrates and microfluidic SERS
      devices. Using these novel lateral-flow paper SERS devices, we achieved detection
      limits as low as 95 fg of Rhodamine 6G (R6G), 413 pg of the organophosphate
      malathion, 9 ng of heroin, and 15 ng of cocaine. Moreover, the measurements show
      that the technique is quantitative and is repeatable across multiple swabs and
      dipsticks. The results reported here may lead to ultra-low-cost portable
      applications in trace chemical detection.

PMID- 23001260
TI  - High prevalence of sexual concurrency and concurrent unprotected anal intercourse
      across racial/ethnic groups among a national, Web-based study of men who have sex
      with men in the United States.
AB  - BACKGROUND: Men who have sex with men (MSM) are the largest human
      immunodeficiency virus (HIV) risk group in the United States. Sexual concurrency
      may contribute to high HIV incidence or to racial/ethnic HIV disparities among
      MSM. Limited information is available on concurrency and racial/ethnic
      differences among MSM or on the extent to which MSM engage in concurrent
      unprotected anal intercourse (UAI). METHODS: Data are from baseline responses in
      a prospective online study of MSM aged 18 years or older, having 1 or more male
      sex partners in the past 12 months, and recruited from social networking Web
      sites. Pairwise sexual concurrency and UAI in the previous 6 months among up to 5
      recent partners was measured, using an interactive questionnaire. Period
      prevalences of concurrency and concurrent UAI were computed and compared across
      racial/ethnic groups at the individual and triad (a respondent and 2 sex
      partners) levels. RESULTS: A total of 2940 MSM reported on 8911 partnerships; 45%
      indicated concurrent partnerships, and 16% indicated concurrent UAI in the
      previous 6 months. Respondents were more likely to have UAI with 2 partners when
      they were concurrent, compared to serially monogamous (odds ratio, 1.93, 95%
      confidence interval, 1.75-2.14). No significant differences in levels of
      individual concurrency or concurrency among triads were found between non
      Hispanic white, non-Hispanic black, and Hispanic men. CONCLUSIONS: Concurrency
      and concurrent UAI in the previous 6 months was common. Although there were no
      differences by race/ethnicity, the high levels of concurrency and concurrent UAI
      may be catalyzing the transmission of HIV among MSM in general.

PMID- 23001261
TI  - Timing of incident STI relative to sex partner change in young women.
AB  - Among adolescents, partner changes are associated with STIs, but little is known
      about the timing. Using daily diaries and weekly STI tests, we describe whether
      infections occur before or after sex partner change during periods when a young
      woman changes partners once. Results showed infections occurring both before and
      after partner changes.

PMID- 23001262
TI  - Is HIV prevalence declining in southern India? Evidence from two rounds of
      general population surveys in Bagalkot District, Karnataka.
AB  - OBJECTIVES: To assess the levels and trends in the prevalence of HIV and sexually
      transmitted infections in the general population in Bagalkot district using 2
      cross-sectional surveys undertaken in 2003 and 2009. METHODS: In both surveys, a
      target sample of 6600 adult males and females was selected systematically from a
      sample of 10 rural villages and 20 urban blocks in 3 of the 6 talukas
      (subdistrict units) in the district. Urine and blood samples were collected from
      all consenting participants for HIV and sexually transmitted infection testing.
      Changes in HIV prevalence in age subgroups were determined by logistic
      regression, taking into account the survey design. RESULTS: HIV prevalence fell
      not significantly from 3.2% to 2.5% during the 6-year study period. It decreased
      significantly (P = 0.023) among persons aged 15 to 24 years, from 2.4% in 2003
      (95% confidence interval [95% CI]: 1.2-3.7) to 1.3% in 2009 (95% CI: 0.6 -2.0).
      However, among males aged 35 and above, HIV prevalence increased significantly (P
      = 0.008), from 3.0% (95% CI: 1.1-4.8) to 4.2% (95% CI: 1.8-6.6), a level similar
      to that found in the younger age-group in 2003. CONCLUSIONS: We observed a
      significant decline in HIV prevalence among people aged 15 to 24 years, where HIV
      prevalence more closely reflects incidence. The increase in HIV prevalence among
      older males may have been because of the aging of a cohort of men among whom HIV
      prevalence was highest in the 2003 survey. It may also have in part reflected
      increased survival, as a result of the scaling up of antiretroviral treatment
      programs throughout the district and state.

PMID- 23001263
TI  - Predictors of male partner treatment for sexually transmitted infection.
AB  - BACKGROUND: Patient-initiated notification is a commonly used practice for
      notifying sex partners of possible exposure to a sexually transmitted infection
      (STI); however, 46% to 75% of partners are never treated. The Contraceptive
      CHOICE Project (CHOICE) is a longitudinal cohort study of women that provides no
      cost contraception, STI testing, treatment to participants, and free partner
      treatment. Our objective was to evaluate characteristics of women who tested
      positive for chlamydia, gonorrhea, or trichomoniasis, and their association with
      successful partner treatment. METHODS: We analyzed baseline survey and STI
      testing, notification, and treatment data from the first 5087 participants
      enrolled in CHOICE. We considered "treated partners" to be men who received
      antibiotic treatment at the study clinic or by a prescription through the study.
      Independent predictors of successful partner treatment were identified using
      univariate analysis and multivariable analysis using Poisson regression with
      robust error variance. RESULTS: Forty-four percent of male partners were
      successfully treated. Women whose partners were less likely to obtain treatment
      were black (adjusted Relative Risk (RR adj) RR adj = 0.6; 95% confidence interval
      [CI]: 0.5-0.8) or reported some concern about future STI with the partner (RR adj
      = 0.6; 95% CI: 0.4, 0.8). Women whose partners were more likely to receive
      treatment were living with their partner (RR adj = 1.4; 95% CI: 1.1-1.8) or
      reported recent inconsistent condom use (RR adj = 1.5; 95% CI: 1.1-2.1).
      CONCLUSIONS: The male partner treatment rate resulting from female patient
      initiated partner notification in our study was low. Our findings highlight the
      need to develop novel notification interventions that yield higher partner
      treatment rates and consider patient-specific factors, such as race and
      relationship status.

PMID- 23001264
TI  - Understanding out-migration among female sex workers in South India.
AB  - BACKGROUND: Migrant sex workers are known to be vulnerable to HIV. There is
      substantial female sex worker (FSW) mobility between the borders of Maharashtra
      and Karnataka, but little programming emphasis on migrant FSWs in India. We
      sought to understand the individual/cultural, structural, and contextual
      determinants of migration among FSWs from Karnataka. METHODS: A cross-sectional
      face-to-face interview of 1567 FSWs from 142 villages in 3 districts of northern
      Karnataka, India was conducted from January to June 2008. Villages having 10+
      FSWs, a large number of whom were migrant, were selected following mapping of
      FSWs. Multinomial logistic regression was conducted to identify characteristics
      associated with migrant (travelled for >= 2 weeks outside the district past year)
      and mobile (travelled for <2 weeks outside the district past year) FSWs;
      adjusting for age and district. RESULTS: Compared with nonmigrants, migrant FSWs
      were more likely to be brothel than street based (Adjusted Odds Ratio (AOR): 5.7;
      95% confidence interval: 1.6-20.0), have higher income from sex work (Adjusted
      Odds Ratio (AOR): 42.2; 12.6-142.1), speak >2 languages (AOR: 5.6; 2.6-12.0),
      have more clients (AOR per client: 2.9; 1.2-7.2), and have more sex acts per day
      (AOR per sex act: 3.5; 1.3-9.3). Mobile FSWs had higher income from sex work
      (AOR: 13.2; 3.9-44.6) relative to nonmigrants, but not as strongly as for migrant
      FSWs. CONCLUSION: Out-migration of FSWs in Karnataka was strongly tied to sex
      work characteristics; thus, the structure inherent in sex work should be
      capitalized on when developing HIV preventive interventions. The important role
      of FSWs in HIV epidemics, coupled with the potential for rapid spread of HIV with
      migration, requires the most effective interventions possible for mobile and
      migrant FSWs.

PMID- 23001265
TI  - Treponema pallidum azithromycin resistance in Dublin, Ireland.
AB  - This study aimed to reassess rates of syphilis azithromycin resistance in Dublin.
      Of the 104 samples, 36 (34.6%) were positive for Treponema pallidum DNA by
      polymerase chain reaction. Thirty samples were analyzed for A2058G mutation, 29
      samples sequenced. Of the 29 samples, 27 (93.1%) had the mutation. Azithromycin
      cannot be recommended for the treatment of syphilis in Dublin.

PMID- 23001266
TI  - Etiologic pattern of genital ulcers in Lusaka, Zambia: has chancroid been
      eliminated?
AB  - BACKGROUND: Genital ulcers are a public health problem in developing countries.
      The World Health Organization recommends the use of syndromic guidelines for
      sexually transmitted infection treatment in resource-constrained countries.
      Monitoring local etiologies provides information that may aid policy for sexually
      transmitted infection treatment. We investigated the etiology of genital ulcer
      disease among outpatients in Lusaka, Zambia. METHODOLOGY: Swabs from genital
      ulcers of 200 patients were tested using polymerase chain reaction for Treponema
      pallidum, herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), Haemophilus
      ducreyi, and Chlamydia trachomatis. RESULTS: The prevalence of the detected
      pathogens was as follows; HSV-2, 28%; T. pallidum, 11.5%; C. trachomatis, 3%; HSV
      1, 0.5%; and H. ducreyi, 0%. Coinfection with HSV-2 and T. pallidum was 1.5%, and
      coinfection of HSV-2 and C. trachomatis was 1%. In 55% of the patients, no
      etiologic diagnosis could be established. CONCLUSIONS: H. ducreyi was not
      detected, whereas HSV-2 and T. pallidum were the commonest pathogens.
      Nondetection of H. ducreyi requires further studies. If the present findings are
      validated, treatment guidelines would require to be revised in Zambia.

PMID- 23001268
TI  - Prevalence of HIV/STIs and associated factors among men who have sex with men in
      An Giang, Vietnam.
AB  - BACKGROUND: The prevalence of HIV and sexually transmitted infections among men
      who have sex with men (MSM) has increased substantially in Vietnam. This study
      aimed to estimate the prevalence of HIV, syphilis, urethral gonorrhoea, and
      urethral chlamydia, and determined correlates of HIV infection among MSM in An
      Giang, Vietnam. METHODS: A group of 381 MSM were recruited in a community-based
      cross-sectional survey between August and December 2009. Face-to-face interviews
      were conducted for collecting data on sociodemographics, behaviors, and access to
      HIV prevention programs. Serological tests for HIV and syphilis and polymerase
      chain reaction for gonorrhoea/chlamydia were performed. Multivariate regression
      analyses were used to investigate the correlates of HIV infection. RESULTS: The
      prevalence of HIV, syphilis, gonorrhoea, chlamydia, and gonorrhoea/chlamydia were
      6.3%, 1.3%, 1.8%, 3.2%, and 4.7%, respectively. HIV prevalence among 63 injecting
      MSM was significantly higher than that of 318 noninjectors (20.6% vs. 3.5%, P <
      0.001). Approximately 40.4% identified as heterosexual and 42.8% had ever had sex
      with females. The rate of unprotected anal intercourse with another male in the
      last month was substantially high (75.3%). Injecting drugs (adjusted prevalence
      ratio [aPR] = 2.88, 95% confidence interval [CI]: 1.12-7.42), being transgender
      (aPR = 4.27, 95% CI, 1.17-15.57), and unprotected sex with a female sex worker
      (aPR = 4.88, 95% CI: 1.91-12.50) were significantly associated with HIV
      infection. The infection risk increased with age to a peak of 25 years and then
      decreased. CONCLUSIONS: Although prevalence levels are lower in An Giang, Vietnam
      than in some other comparable locations, HIV/sexually transmitted infections
      prevention, and sexual health promotion targeting MSM are highly important in
      this location.

PMID- 23001267
TI  - Prevalence of the 23S rRNA A2058G point mutation and molecular subtypes in
      Treponema pallidum in the United States, 2007 to 2009.
AB  - BACKGROUND: The 23S rRNA A2058G point mutation in Treponema pallidum is
      associated with macrolide antibiotic treatment failure. Its prevalence and
      potential association with a molecular subtype within the United States are
      unknown. METHODS: During 2007 to 2009, 11 clinics across the United States sent
      samples from genital ulcers to the Centers for Disease Control and Prevention.
      Molecular techniques were used to identify T. pallidum DNA sequences, the A2058G
      mutation, and subtype of T. pallidum. Accompanying epidemiologic information was
      abstracted from medical records. RESULTS: A total of 141 samples with T. pallidum
      were collected from individuals whose median age was 33 years (range, 13-68
      years): 118 were male (69% reported as men having sex with men [MSM]). The A2058G
      mutation was carried in 75 samples (53%) with T. pallidum, with samples from MSM
      (versus women and other men) more likely carrying the A2058G mutation (65/82
      samples versus 8/57 samples; prevalence ratio, 5.7; 95% confidence interval, 2.9
      10.8). Of 98 strain-typed samples, 61 (62%) were the 14d9 subtype of T. pallidum,
      which was also associated with samples with T. pallidum from MSM (prevalence
      ratio, 3.5; 95% confidence interval, 1.9-6.5). However, among T. pallidum from
      MSM, the A2058G mutation was not associated with the 14d9 subtype. CONCLUSIONS:
      The A2058G mutation and 14d9 subtype of T. pallidum were present throughout the
      United States. Both were more commonly found in T. pallidum from MSM compared
      with women or other men but were not associated with each other. Treating
      syphilis with azithromycin should be done cautiously and only when treatment with
      penicillin or doxycycline is not feasible.

PMID- 23001269
TI  - Retrospective analysis of antimicrobial susceptibility trends (2000-2009) in
      Neisseria gonorrhoeae isolates from countries in Latin America and the Caribbean
      shows evolving resistance to ciprofloxacin, azithromycin and decreased
      susceptibility to ceftriaxone.
AB  - BACKGROUND: The emergence of resistance and treatment failures to third
      generation cephalosporins prompted the revitalization of the global Gonococcal
      Antimicrobial Surveillance Program (GASP) to ensure that information regarding
      trends of the antimicrobial susceptibility of Neisseria gonorrhoeae isolates is
      up-to-date. Accordingly, former and potential GASP participants in Latin America
      and the Caribbean were contacted to reinitiate the GASP network in the region and
      to undertake a retrospective analysis of the antimicrobial susceptibility of N.
      gonorrhoeae isolates between 2000 and 2009. METHODS: Eleven countries
      participated in this retrospective analysis reporting on the susceptibility of N.
      gonorrhoeae isolates to up to 6 antibiotics as well as national treatment
      guidelines over the period. Antimicrobial susceptibility determination was
      carried out using combination of agar dilution and disk diffusion (Clinical
      Laboratory and Standards Institute) or Etest. Antimicrobial susceptibility data
      from each country were aggregated and analyzed for antimicrobial resistance
      trends in the region. RESULTS: More than 11,400 N. gonorrhoeae isolates were
      tested for antimicrobial susceptibility: 6 countries tested N. gonorrhoeae over
      the entire period and 5 countries tested sporadically. Decreased susceptibility
      to ceftriaxone was reported from 1 country (7 isolates, MICs >0.25 MUg/ml) in
      2007. No resistance to spectinomycin was reported. From 2000 to 2009, aggregated
      ciprofloxacin resistance increased from 2% (19/784) to 31% (311/1015) in 9
      countries and azithromycin resistance increased from 6% (39/646) to 23% (225/962)
      in 4/6 reporting countries. Overall, resistance to penicillin and tetracycline
      decreased from 35% (441/1241) to 26% (258/975) and from 60% (476/792) to 35%
      (323/931), respectively.In 2009, resistance to gentamicin (3%, 4/122),
      chloramphenicol (5%, 6/120), and ofloxacin (2%, 6/120) was reported from 1
      country. CONCLUSIONS: The report of ceftriaxone-resistant isolates coupled with
      the emergence and spread of resistance to ciprofloxacin and azithromycin in Latin
      America and the Caribbean in the 2000s indicates the importance of active
      surveillance of N. gonorrhoeae antimicrobial susceptibility to determine
      antimicrobial resistance emerging trends so as to promptly inform and guide the
      development of effective treatment options for gonococcal infections.

PMID- 23001270
TI  - [Inspection of dose reduction in patients during percutaneous coronary
      intervention and catheter ablation procedures].
AB  - With an increasing number of interventional radiology (IVR) procedures, it is a
      critical issue to control and reduce the radiation dose for patients by
      radiological technologists. In our study, we analyzed the usefulness of a
      provision for radiation reduction on catheter ablation and percutaneous coronary
      intervention (PCI) procedures based on the data from radiation information system
      (RIS). With regard to catheter ablation, 50% reduction was enabled with
      decreasing fluoroscopic and radiographic conditions regardless of each technique.
      Radiation reduction enabled a decrease in the fluoroscopic dose during PCI
      procedure. However, note that excessive radiation reduction does not show
      positive results of the radiation dose reduction. Moreover it leads to an
      increase in fluoroscopic time.

PMID- 23001271
TI  - [Investigation of radiofrequency heating for a closed conducting loop formed in a
      part of the patient's body in 1.5 Tesla magnetic resonance (MR) imaging and 3.0
      Tesla MR imaging-measurement of temperature by use of human body-equivalent
      phantom].
AB  - Thermal injuries have been sometimes reported due to a closed conducting loop
      formed in a part of the patient's body during magnetic resonance imaging (MRI).
      In recent years, 3.0 T-MRI scanner has been widely used. However, it is
      considered that the specific absorption rate (SAR) of 3.0 T-MRI can affect the
      heat of the loop because its own SAR becomes approximately 4 times as much as
      that of the1.5 T-MRI scanner. With this, the change in temperature was measured
      with human body-equivalent loop phantom in both 1.5 T-MRI and 3.0 T-MRI. In the
      two scanners, the temperature during 20 min of scanning time was measured with
      three types of sequences such as field echo (FE), spin echo (SE), and turbo SE
      (TSE) set up with the same scanning condition. It was found from the result that
      rise in temperature depended on SAR of the scanning condition irrespective of
      static magnetic field intensity and any pulse sequences. Furthermore, the
      increase of SAR and rise in temperature were not only in proportion to each other
      but also were indicated to have good correlation. However, even low SAR can
      occasionally induce serious thermal injuries. It was found from result that we
      had to attempt not to form a closed conducting loop with in a part of the
      patient's body during MRI.

PMID- 23001272
TI  - [Comparison of diffusion tensor imaging-derived fractional anisotropy in multiple
      centers for identical human subjects].
AB  - The fractional anisotropy (FA) is calculated by using diffusion tensor imaging
      (DTI) with multiple motion probing gradients (MPG). While FA has become a widely
      used tool to detect moderate changes in water diffusion in brain tissue, the
      measured value is sensitive to scan parameters (e.g. MPG-direction, signal to
      noise ratio, etc.). Therefore, it is paramount to address the reproducibility of
      DTI measurements among multiple centers. The purpose of this study was to assess
      the inter-center variability of FA. We studied five healthy volunteers who
      underwent DTI brain scanning three times at three different centers (I-III), each
      with a 1.5 T scanner having a different MPG-schema. Then, we compared the FA and
      eigenvalue from the three centers measured in seven brain regions: splenium of
      corpus callosum (CCs), genu of corpus callosum (CCg), putamen, posterior limb of
      internal capsule, cerebral peduncle, optic radiation, and middle cerebellar
      peduncle. At the CCs and CCg, there was a statistical difference (p<0.05) between
      center Iand center IIfor the same MPG-directions. Furthermore, at CCs and CCg,
      there was a statistical difference (p<0.05) between center II and center III for
      different MPG-directions. Conversely, no statistical differences were found
      between center I and center III for the different MPG-directions for all regions.
      These results indicate that the FA value was affected by the MPG-schema as well
      as by the MPG-directions.

PMID- 23001273
TI  - [Examination of the effectiveness of heart rate control using intravenous beta
      blocker in 64-slice coronary computed tomography angiography].
AB  - The purpose of this study is to clarify the effectiveness of the use of beta
      blocker in coronary computed tomography angiography (CCTA). In 1783 patients,
      heart rate was controlled by propranolol injection to patients with heart rates
      of 61 bpm or more. As a result, the scan heart rate (58.8+/-6.5 bpm) decreased
      significantly compared with the initial heart rate (72.7+/-9.4 bpm). Prospective
      gating method was used by 61.9% including 64.3% of the intravenous beta-blocker
      injection group. Moreover, daily use of oral beta-blocker had influence on
      reduction of the scan heart rate (daily use group: 60.1+/-6.5 bpm vs. unuse
      group: 58.5+/-6.3 bpm p<0.01). When we evaluated the image quality of CCTA by the
      score, the improvement of the score was obviously admitted by 65 bpm or less of
      the scan heart rate. The ratio of scan heart rate that was controlled by 65 bpm
      or less was decreased in the initial heart rate groups that were 81 bpm or more.
      The incidence of adverse reactions by the propranolol injection was few, and
      these instances only involved slight symptoms. Therefore, heart rate control with
      the use of beta-blocker is useful for the image quality improvement of CCTA. This
      form of treatment can be safely enforced.

PMID- 23001274
TI  - [Summary of results of the patient exposures in diagnostic radiography in 2011
      questionnaire-focus on radiographic conditions-].
AB  - We carried out a questionnaire survey to research on radiographic conditions in
      3000 institutes. We discussed on radiographic conditions to estimate patient
      exposures. The collection rate was 24.7%. Most of the institutes shifted to the
      use of high-voltage generator, digital devices, and filmless equipment. We did
      not see a shift in this survey of radiographic conditions compared with the 2007
      survey.

PMID- 23001275
TI  - [Effects of region of interest settings in signal-to-noise ratio measurement of
      clinical images using arrays of multiple receiver coils].
AB  - In many clinical imaging procedures using arrays of multiple receiver coils, a
      uniform sensitivity process is performed using the sensitivity distribution from
      the body coil. This causes the noise to be uneven, and background noise cannot be
      used when measuring the signal-to-noise ratio (SNR). The SNR of clinical images
      with sensitivity correction using arrays of multiple receiver coils sets the
      region of interest (ROI) in the region where the signal is uniform, and is
      limited to the identical ROI method where measurements are taken with noise from
      the identical region. When SNR is measured with the identical ROI method, uneven
      noise caused by sensitivity correction as well as the signal strength
      distribution within the ROI of the object is reflected in the noise. Therefore,
      evaluation must be performed in as localized a position as possible. Measurement
      error becomes small on images with higher resolution, and if ROI larger than
      10*10 pixels can be set in a region of even signal, SNR measurement of clinical
      images with less underestimation may be possible.

PMID- 23001276
TI  - [Introduction of Japan Medical Imaging and Radiological Systems Industries
      Association (JIRA)].

PMID- 23001278
TI  - Controlled exposure to diesel exhaust causes increased nitrite in exhaled breath
      condensate among subjects with asthma.
AB  - OBJECTIVE: To determine whether oxidative/nitrosative stress plays a role in the
      acute effects of diesel exhaust (DE) on subjects with asthma. METHODS: In this
      crossover study, 16 subjects with mild to moderate asthma were exposed to clean
      filtered air or diluted DE (300 MUg/m as PM2.5) for 1 hour with intermittent
      exercise. RESULTS: Airway hyperreactivity increased 24 hours after exposure to DE
      compared with clean filtered air (PC20, 14.9 mg/mL vs 19.7 mg/mL; P = 0.012).
      Nitrite in exhaled breath condensate was elevated immediately after diesel
      exposure (P = 0.052) and remained elevated 4 and 24 hours after exposure.
      CONCLUSIONS: After exposure to DE, subjects with asthma demonstrated increased
      airway hyperreactivity and obstruction. Increased nitrite in exhaled breath
      condensate, in the absence of increased exhaled nitric oxide, suggests a
      noninflammatory oxidative stress mechanism by which DE affects the lung.

PMID- 23001279
TI  - The effect of the US Medicare Part D coverage gaps on medication use among
      patients with depression and heart failure.
AB  - BACKGROUND: Medication use among Medicare beneficiaries has increased and
      adherence has improved since the implementation of the Medicare Part D
      prescription drug benefit in 2006. However, the structure of the benefit,
      particularly, the coverage gap, is still problematic. It is critical to
      understand how beneficiaries with coexisting conditions respond to the coverage
      gap and whether their response differs by type of medications. AIMS OF THE STUDY:
      The paper aims to evaluate the effects of Medicare Part D's coverage gap on drug
      regimens among beneficiaries with coexisting depression and heart failure (HF).
      METHODS: Drug utilization patterns and medication adherence of a 5% random sample
      of Medicare Part D beneficiaries with depression and HF in 2007 were observed.
      Drug utilization patterns were measured on the basis of reported drug claims and
      medication adherence was defined as the proportion of days of medication
      possession in a given period. We compared pre-post drug use patterns and
      medication adherence across three groups: no coverage, generic coverage, and full
      coverage due to low-income subsidies (LIS) and used propensity score weighting to
      adjust for difference across groups. RESULTS: Beneficiaries with some drug
      coverage in the gap were more likely to enter the gap: 82% for LIS, 79% for
      generic-only and 58% for no coverage. Beneficiaries without drug coverage reduced
      their use of antidepressants by 5.0% (95% CI 1.7%-8.2%), and HF drugs by 9.4%
      (95% CI 7.2%-11.5%) after they entered the coverage gap. Those with generic
      coverage cut their brand-name drugs more than generic drugs but did not shift to
      generic drugs. However, adherence to antidepressants did not change; adherence to
      HF drugs reduced slightly, 2.5% (95% CI 1.2%-3.7%) in the no-coverage group and
      2.6% (95% CI 1.3%-3.9%) in the generic-coverage group. CONCLUSIONS: The coverage
      gap was associated with a modest reduction in number of prescriptions filled for
      depression and HF but it was not associated with a significant effect on
      adherence. IMPLICATIONS FOR HEALTH POLICY: We found that beneficiaries with
      coexisting depression and HF were less likely to reduce their drug use than
      beneficiaries in general. In addition, the gap was not associated with a large
      reduction in adherence. It suggests that concerns about the coverage gap's
      harmful effects on medication adherence, or comorbidities might be overstated.
      IMPLICATIONS FOR FURTHER RESEARCH: Further studies on how people make medication
      use decisions in the face of changes in benefits and how the coverage affects non
      drug medical outcomes are warranted.

PMID- 23001280
TI  - ADHD medication use following FDA risk warnings.
AB  - BACKGROUND: In 2006, the U.S. Food and Drug Administration (FDA) investigated
      cardiac and psychiatric risks associated with attention deficit/hyperactivity
      disorder (ADHD) medication use. AIMS OF THE STUDY: To examine how disclosure of
      safety risks affected pediatric ADHD use, and to assess news media coverage of
      the issue to better understand trends in treatment patterns. METHODS: We used the
      AHRQ's Medical Expenditure Panel Survey (MEPS), a nationally representative
      household panel survey, to calculate unadjusted rates of pediatric ADHD use from
      2002 to 2008 overall and by parents' education. We examined whether children
      (ages 0 to 20) filled a prescription for any ADHD medication during the calendar
      year. Next, we used content analysis methods to analyze news coverage of the
      issue in 10 high-circulation newspapers, the 3 major television networks and a
      major cable news network in the U.S. We examined 6 measures capturing information
      conveyed on risk and benefits of ADHD medication use. RESULTS: No declines in
      medication use following FDA safety warnings overall or by parental education
      level were observed. News media coverage was relatively balanced in its portrayal
      of the risks and benefits of ADHD medication use by children. DISCUSSION: ADHD
      risk warnings were not associated with large declines in medication use, and
      balanced news coverage may have contributed to the treatment patterns observed.
      Self-reported surveys like the MEPS rely on the recall of respondents and may be
      subject to reporting bias. However, the validity of these data is supported by
      their consistency with other data on drug use from other sources. IMPLICATIONS
      FOR HEALTH CARE PROVISION AND USE: These findings are in direct contrast to the
      substantial declines in use observed after pediatric antidepressant risk warnings
      in the context of a news media environment that emphasized risks over benefits.
      IMPLICATIONS FOR HEALTH POLICIES: Our findings are relevant to the ongoing
      discussion about improving the FDA's ability to monitor drug safety. Safety
      warnings occur amid ongoing concern that the agency has insufficient authority
      and resources to fulfill its mission to protect the public's health. Efforts to
      bolster the FDA's post-marketing surveillance system have the potential to
      incorporate more data in decision making to allow for earlier detection of health
      risks. IMPLICATIONS FOR FURTHER RESEARCH: Further research is needed to assess
      whether other treatment changes occurred following risk warnings. For example, it
      is important to determine whether an increase in cardiac screening prior to
      medication initiation occurred. Likewise, the FDA advises that children
      experiencing hallucinations or other psychiatric responses to medication be
      discontinued from drug treatment. If it is determined that instead of being
      discontinued from medication treatment, children experiencing hallucinations are
      put on additional medication (e.g., antipsychotics), additional efforts by the
      FDA to better inform the public are warranted.

PMID- 23001281
TI  - Does co-morbid depression impact diabetes related costs? Evidence from a cross
      sectional survey in a low-income country.
AB  - AIMS OF THE STUDY: The economic implications of co-morbid depression in patients
      with chronic medical disorders have been studied mainly in high-income countries.
      However, the applicability of such findings in developing countries cannot be
      assumed. In the present study we estimate diabetes related costs and explore the
      link between depression and diabetes related costs in Romania. In this former
      communist country, the general perception of practitioners and policy-makers is
      that psychological issues are far less important than medical concerns for
      patients with diabetes, a perception that may lead to the misallocation of
      already scarce resources. METHODS: Data related to costs of diabetes care and to
      co-morbid depression were collected from a sample of 1,171 diabetes patients at
      the Nutrition and Diabetes Center in Cluj-Napoca, Romania, using the Diabetes
      Costs Questionnaire (DCQ) and the Patient Health Questionnaire 9 (PHQ9). The
      gathered data were subjected to a bivariate analysis of the depression-cost
      relationship, as well as a regression analysis in order to isolate the effect of
      depression on diabetes related costs from the effect of covariates. RESULTS:
      Direct and indirect diabetes related costs equally contributed to the total
      costs. The repartition of the cost burden between the public system and private
      agents is nearly equal as well. The bivariate analysis of the depression-cost
      relationship reveals statistically significant larger diabetes related costs for
      patients with major depression than for patients with minor depression, and the
      latter have larger diabetes related costs than patients free of depression
      symptoms. When the pure effect of depression on diabetes related costs was
      isolated by means of regression techniques, the provisional diagnosis of major
      depression was found to significantly increase diabetes related costs.
      DISCUSSION: The equal distribution of diabetes related costs between direct and
      indirect measures, as well as the cost burden equally split between the public
      system and private agents can be explained by the costs of medication and the
      costs associated with time lost by the non-compensated caregivers. Consistent
      with Romanian cultural traditions, most of the patients rely on their relatives
      in an informal diabetes caregiving market for assistance. Alongside depression,
      the multivariate analysis revealed that factors such as Hungarian ethnicity,
      income, and number of years since diagnosis also significantly contribute to
      diabetes related costs. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Findings
      that depression increases diabetes related costs bear potential implications for
      health policies and health care provision (i.e., the effect of depression on
      costs can be minimized by adequate recognition and treatment). As such, screening
      and treatment of co-occurring depression in diabetes patients should become part
      of the diabetes treatment protocol, not only in Romania but in other Central and
      Eastern European countries as well.

PMID- 23001282
TI  - Estimating the costs of psychiatric hospital services at a public health facility
      in Nigeria.
AB  - BACKGROUND: Information on the cost of mental health services in Africa is very
      limited even though mental health disorders represent a significant public health
      concern, in terms of health and economic impact. Cost analysis is important for
      planning and for efficiency in the provision of hospital services. STUDY AIM: The
      study estimated the total and unit costs of psychiatric hospital services to
      guide policy and psychiatric hospital management efficiency in Nigeria. METHODS:
      The study was exploratory and analytical, examining 2008 data. A standard costing
      methodology based on ingredient approach was adopted combining top-down method
      with step-down approach to allocate resources (overhead and indirect costs) to
      the final cost centers. Total and unit cost items related to the treatment of
      psychiatric patients (including the costs of personnel, overhead and annualised
      costs of capital items) were identified and measured on the basis of outpatients'
      visits, inpatients' days and inpatients' admissions. The exercise reflected the
      input-output process of hospital services where inputs were measured in terms of
      resource utilisation and output measured by activities carried out at both the
      outpatient and inpatient departments. In the estimation process total costs were
      calculated at every cost center/department and divided by a measure of
      corresponding patient output to produce the average cost per output. This
      followed a stepwise process of first allocating the direct costs of overhead to
      the intermediate and final cost centers and from intermediate cost centers to
      final cost centers for the calculation of total and unit costs. Costs were
      calculated from the perspective of the healthcare facility, and converted to the
      US Dollars at the 2008 exchange rate. RESULTS: Personnel constituted the greatest
      resource input in all departments, averaging 80% of total hospital cost,
      reflecting the mix of capital and recurrent inputs. Cost per inpatient day, at
      $56 was equivalent to 1.4 times the cost per outpatient visit at $41, while cost
      per emergency visit was about two times the cost per outpatient visit. The cost
      of one psychiatric inpatient admission averaged $3,675, including the costs of
      drugs and laboratory services, which was equivalent to the cost of 90
      outpatients' visits. Cost of drugs was about 4.4% of the total costs and each
      prescription averaged $7.48. The male ward was the most expensive cost center.
      Levels of subsidization for inpatient services were over 90% while ancillary
      services were not subsidized hence full cost recovery. CONCLUSION: The hospital
      costs were driven by personnel which reflected the mix of inputs that relied most
      on technical manpower. The unit cost estimates are significantly higher than the
      upper limit range for low income countries based on the WHO-CHOICE estimates.
      Findings suggest a scope for improving efficiency of resource use given the high
      proportion of fixed costs which indicates excess capacity. Adequate research is
      needed for effective comparisons and valid assessment of efficiency in
      psychiatric hospital services in Africa. The unit cost estimates will be useful
      in making projections for total psychiatric hospital package and a basis for
      determining the cost of specific neuropsychiatric cases.

PMID- 23001283
TI  - Synthesis, characterization and cytotoxicity of a carboxylic ligand 2,2-bis(3
      phenylpropyl) malonic acid and a corresponding Mn(II) complex.
AB  - The organic ligand Hbpmc and the polymeric complex [Mn(bpmc)(2)(4,4'
      bipy)(H(2)O)(2)](n).3H(2)O (4,4'-bipy = 4,4'-bipyridine, Hbpmc = 2,2-bis(3
      phenylpropyl) malonic acid), which have both a lipophilic group (aromatic ring)
      and a hydrophilic group (non-coordination carboxyl), were synthesized and
      characterized by IR spectra, elemental analysis and X-ray single-crystal
      diffraction. The interaction of the complexes with HC-DNA was investigated by
      fluorescence spectroscopy. Gel electrophoresis assay demonstrates the ability to
      cleave the extracted HC-DNA. The value of IC(50) is to understand the effect of
      cytotoxic activity which is lower than cisplatin and higher than the ligand
      Hbpmc. The apoptotic tests show that the complexes apparently have an apoptotic
      effect on Hela cells.

PMID- 23001284
TI  - Three-month evaluation of dorzolamide hydrochloride/timolol maleate fixed
      combination eye drops versus the separate use of both drugs.
AB  - PURPOSE: To investigate the ocular hypotensive effect and safety of dorzolamide
      hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops. METHODS: The
      study cohort comprised 34 patients with either primary open-angle glaucoma or
      ocular hypertension who were being concomitantly treated with dorzolamide
      hydrochloride 1 % eye drops and timolol maleate 0.5 % eye drops. The dorzolamide
      hydrochloride 1 % and timolol maleate 0.5 % eye drops were replaced with
      dorzolamide hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops
      without any washout period. The intraocular pressure (IOP) was evaluated both
      before and 1 and 3 months after the treatment change. The patients were asked to
      complete a questionnaire on adherence to the treatment protocol 1 month after the
      change in treatment. RESULTS: The IOP was 15.5 +/- 2.7 mmHg at the time of
      treatment change, 15.2 +/- 2.7 mmHg at 1 month post-change, and 15.5 +/- 2.9 mmHg
      at 3 months post-change, which is consistent with that before the treatment
      change (p = 0.286). Based on the completed questionnaire, following the treatment
      change, 50 % of patients felt a stinging sensation following administration of
      the eye drops and 11.8 % experienced blurred vision. In no case were the eye
      drops discontinued due to adverse reactions or insufficient IOP decrease.
      CONCLUSION: The replacement of concomitant treatment with dorzolamide
      hydrochloride 1 % and timolol maleate 0.5 % eye drops with dorzolamide
      hydrochloride 1 %/timolol maleate 0.5 % fixed-combination eye drops improved
      protocol adherence and preserved the IOP.

PMID- 23001286
TI  - Early development of coelomic structures in an echinoderm larva and a similarity
      with coelomic structures in a chordate embryo.
AB  - Early coelomic development in the abbreviated development of the sea urchin
      Holopneustes purpurescens is described and then used in a comparison with
      coelomic development in chordate embryos to support homology between a single arm
      of the five-armed radial body plan of an echinoderm and the single bilateral axis
      of a chordate. The homology depends on a positional similarity between the origin
      of the hydrocoele in echinoderm development and the origin of the notochord in
      chordate development, and a positional similarity between the respective origins
      of the coelomic mesoderm and chordate mesoderm in echinoderm and chordate
      development. The hydrocoele is homologous with the notochord and the secondary
      podia are homologous with the somites. The homology between a single echinoderm
      arm and the chordate axis becomes clear when the aboral to oral growth from the
      archenteron in the echinoderm larva is turned anteriorly, more in line with the
      anterior-posterior axis of the early zygote. A dorsoventral axis inversion in
      chordates is not required in the proposed homology.

PMID- 23001287
TI  - (18)F-FDG uptake at initial staging of the adrenocortical cancers: a diagnostic
      tool but not of prognostic value.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer for which little
      level evidence exists to guide management. (18)F-FDG PET ((18)F
      fluorodeoxyglucose positron emission tomography) is an increasingly used
      diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In
      some other solid tumors, (18)F-FDG PET may offer prognostic information that can
      guide optimal patient treatment. The aim of the present study was to evaluate
      whether preoperative (18)F-FDG PET based on SUVs assessments has a prognostic
      value in ACC patients. METHODS: A retrospective analysis was performed in
      patients who underwent (18)F-FDG PET/CT for the evaluation of ACC. Inclusion
      criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis
      available; (18)F-FDG PET/CT performed prior to surgery or other treatment of the
      primary tumor; a minimum of 6-months follow-up for surviving patients. All (18)F
      FDG PET/CT procedures were reinterpreted in a blind fashion. RESULTS: Thirty
      seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled
      the study criteria. Median uptake values were tumor standardized uptake values
      (SUV)(max) = 11 (range: 3-56) and a tumor/liver SUV(max) ratio = 4.2 (range: 1.3
      15). Median follow-up was 20 months. Although classic risk factors (tumoral
      stage, Weiss score) were associated with poor outcome, there was no correlation
      between primary tumor FDG uptake with overall survival (OS) and disease free
      survival (DFS) in M0 patients and with overall survival in M1 patients. (18)F-FDG
      uptake correlated inconsistently with sinister histological features, such as
      atypical mitoses or necrosis. CONCLUSIONS: At initial staging, primary tumor FDG
      uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient
      prognosis and treatment strategy should not be based on uptake values.

PMID- 23001288
TI  - Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology
      and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac
      Trp53tm1Brd haploinsufficient mice (Feed Studies).
AB  - Senna is used as a stimulant laxative in the management of constipation resulting
      from opioid use or when treatment with bulking or osmotic agents has failed.
      Increased use of senna was expected due to the removal of the stimulant laxatives
      danthron and phenolphthalein from the market. Senna was nominated for study by
      the Center for Drug Evaluation and Research, United States Food and Drug
      Administration (FDA) due to the wide use of laxative preparations, positive
      genotoxicity in vitro for some senna components or metabolites, and unknown
      carcinogenic potential. Because a 2-year rat study was ongoing by the
      manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/
      ) mouse. In this study, the potential for carcinogenic effects of senna was
      studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1
      p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model
      systems for toxicology and carcinogenesis studies, especially those that can
      provide mechanistic information relative to understanding an agents mode of
      action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous
      F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology
      studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse
      peripheral blood erythrocytes.

PMID- 23001289
TI  - Biomedical evaluation of a novel nitrogen oxides releasing wound dressing.
AB  - Chronic wounds are a major cause for both suffering and economical losses.
      Management of chronic non-healing wounds requires multipronged approach. They are
      polymicrobial and agonizing for the patient due to associated pain. Moist
      dressing providing antimicrobial action is a highly desirable chronic wound
      management option. Here we report a hydrogel based dressing that possesses the
      antimicrobial properties of acidified sodium nitrite and the homeostatic property
      of a hydrogel. The dressing was developed by combining citric acid cross-linked
      cotton gauze and sodium nitrite loaded gelatin. The cotton gauze was cross-linked
      with citric acid by pad-dry-curing in presence of nano-titania catalyst. The
      cotton gauze-gelatin hydrogel combination was gamma-irradiated and freeze-dried.
      At the time of application, the freeze-dried dressing is wetted by sodium nitrite
      solution. The dressing has a fluid uptake ability of 90 % (w/v) and the water
      vapour evaporation rate was estimated to be 2,809 +/- 20 g/m(2)/day. The dressing
      showed significant antimicrobial activity against both planktonic and biofilm
      forms and was effective during consecutive re-uses. Cytotoxicity study showed
      inhibition of fibroblasts, but to a lesser extent than clinically administered
      concentrations of antiseptic like povidone iodine. Storage at 37  degrees C over
      a 3 month period resulted in no significant loss of its antimicrobial activity.

PMID- 23001290
TI  - [Outpatient therapy of post-traumatic stress syndrome by cognitive therapy and
      baclofen].

PMID- 23001291
TI  - [Short QT syndrome].
AB  - Short QT syndrome was first described in 2000. It is a sporadic or familial ion
      channel disease that is associated with abbreviation of the QT interval
      permanently or transiently. The time of first manifestation of symptoms such as
      atrial fibrillation or syncope or even sudden death is between the 2nd and 4th
      decade. Sudden death has also been described for newborns and adolescents.
      Therapy depends on the severity of the symptoms. The therapy of choice for
      secondary prevention of sudden death is the implantable cardioverter
      defibrillator (ICD). Quinidine has been shown to be effective in preventing
      arrhythmias in a number of patients. It is mostly used as an adjunct to the ICD
      but has also been used with considerable success in children and individuals who
      refused ICD implantation.

PMID- 23001292
TI  - The effect of alfentanil versus ketamine on the intubation condition and
      hemodynamics with low-dose rocuronium in children.
AB  - PURPOSE: We investigated the effect of alfentanil and ketamine on the intubation
      condition and hemodynamic parameters during propofol anesthesia with low-dose
      rocuronium in children. METHODS: Fifty-four children, aged 3-9 years undergoing
      tonsillectomy, were randomly allocated to receive either alfentanil 20 MUg/kg
      (alfentanil group, n = 27) or ketamine 0.5 mg/kg (ketamine group, n = 27) 1 min
      before anesthesia induction. Anesthesia was induced with propofol 2.5 mg/kg and
      rocuronium 0.3 mg/kg and maintained with propofol infusion (6 mg/kg/h). The
      neuromuscular relaxation was monitored, and intubation conditions, hemodynamic
      changes, and recovery time were assessed. RESULTS: All patients were successfully
      intubated and there were no significant differences in the intubation conditions
      between alfentanil and ketamine groups. At the time of tracheal intubation, the
      median [inter-quartile range] twitch height was similar between two groups (37 [4
      48] % in the alfentanil group vs. 29 [4-43.5] % in the ketamine group, p =
      0.326). CONCLUSIONS: This study showed that both ketamine 0.5 mg/kg and
      alfentanil 20 MUg/kg provided adequate intubation condition during propofol
      induction with low-dose rocuronium in children. The mean arterial pressure and
      heart rate were higher in the ketamine group after propofol injection but they
      remained within the normal limit in both groups throughout the study period.

PMID- 23001294
TI  - Immunohistochemical examination of Akappa amyloidosis with antibody against
      adjacent portion of the carboxy terminus of immunoglobulin kappa light chain.
AB  - For the purpose of investigating the carboxy terminus distribution of
      immunoglobulin kappa light chain in Akappa amyloid deposits in tissue sections,
      we examined the immunostaining pattern of Akappa amyloidosis with conventional
      rabbit clonal antibody against peptide derived from the C-terminal sequence of
      human kappa light chain. This antihuman kappa light chain clone II (clone H16-E)
      reacted with the adjacent region of the C terminus of the kappa light chain
      constant region in SPOT analysis. Immunohistochemically, this antibody reacted
      with amyloid deposits in all 18 cases of Akappa amyloidosis. In 15 cases, this
      antibody reacted with amyloid deposits almost uniformly. In this study, we
      demonstrated for the fi rst time that the peptides adjacent to the carboxy
      terminus of immunoglobulin kappa light chain or full-length kappa light chain
      were constituents of Akappa amyloidosis, and these molecules were distributed
      uniformly in almost all cases of Akappa amyloidosis in tissue sections.

PMID- 23001293
TI  - Overexpression of p53 protein in human tumors.
AB  - According to the current concept of carcinogenesis, neoplastic transformation
      consists of multistep accumulations of adverse genetic and epigenetic events. p53
      is a transcription factor that regulates cellular response to diverse forms of
      stress through a complex network which monitors genome integrity and cell
      homeostasis. Mutant p53 loss-of-function, dominant-negative, and gain-of-function
      properties have been implicated in the development of a wide variety of human
      cancers, and it is generally accepted that p53 is a component in biochemical
      pathways central to human carcinogenesis. Study of p53 has come to the forefront
      of cancer research, and detection of its abnormalities during the development of
      tumors may have diagnostic, prognostic, and therapeutic implications. In this
      review, we focus on recent research on overexpression of mutant p53 in human
      cancer, with an emphasis on mutant p53 regulation, gain of function of mutant p53
      in transcriptional effects, and the diagnostic, prognostic, and predictive value
      of p53 overexpression in human cancer.

PMID- 23001295
TI  - Immunohistochemical analysis of various serum proteins in living mouse thymus
      with "in vivo cryotechnique".
AB  - It has been difficult to clarify the precise localizations of soluble serum
      proteins in thymic tissues of living animals with conventional immersion- or
      perfusion-fixation followed by alcohol dehydration owing to ischemia and anoxia.
      In this study, "in vivo cryotechnique" (IVCT) followed by freeze-substitution
      fixation was performed to examine the thymic structures of living mice and
      immunolocalizations of intrinsic or extrinsic serum proteins, which were albumin,
      immunoglobulin G1 (IgG1), IgA, and IgM, as well as intravenously injected bovine
      serum albumin (BSA). Mouse albumin was more clearly immunolocalized in blood
      vessels and interstitial matrices of the thymic cortex than in tissues prepared
      by the conventional methods. The immunoreactivities of albumin and IgG1 were
      stronger than those of IgA and IgM in the interstitium of subcapsular cortex. The
      injected BSA was time-dependently immunolocalized in blood vessels and the
      interstitium of corticomedullary areas at 3.5 h after its injection, and then
      gradually diffused into the interstitium of the whole cortex at 6 h and 12 h.
      Thus, IVCT revealed definite immunolocalizations of serum albumin and IgG1 in the
      interstitium of thymus of living mice, indicating different accessibility of
      serum proteins from the corticomedullary areas, not from the subcapsular cortex
      of living animals, depending on various molecular sizes and concentrations.

PMID- 23001296
TI  - Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic
      colitis induced by dextran sulfate sodium.
AB  - Intestinal fibrosis is a common and severe complication of inflammatory bowel
      disease (IBD), especially Crohn's disease (CD). To investigate the therapeutic
      approach to intestinal fibrosis, we have developed a mouse model of intestinal
      fibrosis by administering dextran sulfate sodium (DSS) and examining the effects
      of irsogladine maleate (IM) [2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine
      maleate], which has been widely used as an antiulcer drug for gastric mucosa in
      Japan, on DDS-induced chronic colitis. In this experimental colitis lesion,
      several pathognomonic changes were found: increased deposition of collagen,
      increased number of profibrogenic mesenchymal cells such as fibroblasts
      (vimentin(+), alpha-SMA(-)) and myofibroblasts (vimentin(+), alpha-SMA(+)) in
      both mucosa and submucosa of the colon with infiltrating inflammatory cells, and
      increased mRNA expressions of collagen type I, transforming growth factor (TGF)
      beta, matrix metalloproteinase (MMP)-2, and tissue inhibitor of matrix
      metalloproteinase (TIMP)-1. When IM was administered intrarectally to this
      colitis, all these pathological changes were significantly decreased or
      suppressed, suggesting a potential adjunctive therapy for intestinal fibrosis. IM
      could consequently reduce fibrosis in DSS colitis by direct or indirect effect on
      profibrogenic factors or fibroblasts. Therefore, the precise effect of IM on
      intestinal fibrosis should be investigated further.

PMID- 23001297
TI  - Colocalization of APC and PSD-95 in the nerve fiber as well as in the post
      synapse of matured neurons.
AB  - Adenomatous polyposis coli protein (APC) is highly expressed in the nervous
      tissue, but its function there is not yet known. We previously found that the
      microtubule-bundling activity of APC is stimulated by its interaction with PSD
      95, a neuronal scaffolding protein, in cultured COS-7 cells. In the present
      study, we investigated the distribution and localization of the intrinsic APC and
      PSD-95 in both cultured rat hippocampal neurons and in the rat cerebellum by
      immunofluorescence and immunoelectron microscopy. In cultured neurons, most of
      the PSD-95 immunofluorescence puncta were colocalized with APC, and the APC and
      PSD-95 immunogolds were colocalized in the nerve fibers as well as in the
      postsynaptic site, but not in the presynaptic site. In the molecular layer of the
      rat cerebellum, colocalization of APC and PSD-95 was also detected in the nerve
      fibers and the postsynaptic site, but not in the presynaptic site. Based on these
      results, we conclude that APC and PSD-95 colocalize and bind to form a protein
      complex in nerve fibers as well as in postsynaptic sites in matured neurons,
      suggesting the involvement of the APC/PSD-95 complex in the microtubule functions
      within the nerve fibers and the synapse functions at the postsynaptic site.

PMID- 23001298
TI  - Some fine-structural findings on the thyroid gland in Apc1638T/1638T mice that
      express a C-terminus lacking truncated Apc.
AB  - Adenomatous polyposis coli (Apc) is a multifunctional protein as well as a tumor
      suppressor. To determine the functions of the C-terminal domain of Apc, we
      examined Apc(1638T/1638T) mice that express a truncated Apc lacking the C
      terminal domain. The Apc(1638T/1638T) mice were tumor free and exhibited growth
      retardation. We recently reported abnormalities in thyroid morphology and
      functions of Apc(1638T/1638T) mice, although the mechanisms underlying these
      abnormalities are not known. In the present study, we further compared thyroid
      gland morphology in Apc(1638T/1638T) and Apc(+/+) mice. The diameters of thyroid
      follicles in the left and right lobes of the same thyroid gland of
      Apc(1638T/1638T) mice were significantly different whereas the Apc(+/+) mice
      showed no significant differences in thyroid follicle diameter between these
      lobes. To assess the secretory activities of thyroid follicular cells, we
      performed double-immunostaining of thyroglobulin, a major secretory protein of
      these cells, and the rough endoplasmic reticulum (rER) marker calreticulin. In
      the Apc(1638T/1638T) follicular epithelial cells, thyroglobulin was mostly
      colocalized with calreticulin whereas in the Apc(+/+) follicular epithelial
      cells, a significant amount of the cytoplasmic thyroglobulin did not colocalize
      with calreticulin. In addition, in thyroid-stimulating hormone (TSH)-treated
      Apc(1638T/1638T) mice, electron microscopic analysis indicated less frequent
      pseudopod formation at the apical surface of the thyroid follicular cells than in
      Apc(+/+) mice, indicating that reuptake of colloid droplets containing iodized
      thyroglobulin is less active. These results imply defects in intracellular
      thyroglobulin transport and in pseudopod formation in the follicular epithelial
      cells of Apc(1638T/1638T) mice and suggest suppressed secretory activities of
      these cells.

PMID- 23001299
TI  - Composite paraganglioma and ganglioneuroma in the retroperitoneum: a case report.
AB  - Reports of a composite paraganglioma (PG) and ganglioneuroma (GN) in the
      retroperitoneum are rare. In the present case, dynamic computed tomographic (CT)
      findings showed a 30 * 22 * 20 mm tumor that was located in the retroperitoneum
      and which was dissociated from pancreatic tissue and the left adrenal gland. The
      markedly reddish tumor showed a clear margin and central multicystic changes on
      the cut surface. The tumor was composed of two major components, the PG and the
      GN. The paraganglionic cells in the PG component, which were arranged in a nested
      pattern, occupied the main and central part of the tumor. Both ganglionic cells
      and Schwann cells in the GN were located in a unorganized pattern in the
      periphery. The paraganglionic cells exhibited a Zellballen pattern, which
      consisted of an association of edematous vascular-rich stroma and focal
      hemorrhage, resulting in multicystic changes. These centrally located tumor cells
      were pleomorphic in part and did not have mitotic figures. In the periphery,
      Schwann cells, which were arranged in an obscure and fascicular pattern that was
      intermingled with large ganglionic cells, were located adjacent to the PG
      component with a mostly sharp margin. With higher magnification, the border was
      not as sharp, as revealed especially with chromogranin-A immunostain, in which
      both the PG and GN components were focally intermingled with each other. The
      histogenesis of the composite PG and GN was thought to be extraadrenal neural
      crest cells in the retroperitoneum because the tumor was not located in the
      adrenal gland or the Zuckerkandl organ, according to the CT findings. The
      immunohistochemical findings of this rare case of a composite PG and GN in the
      retroperitoneum are reported with a focus on the peculiar arrangement of these
      two components.

PMID- 23001301
TI  - Dual-mode fluorescence switching induced by self-assembly of well-defined
      poly(arylene ether sulfone)s containing pyrene and amide moieties.
AB  - A new class of fluorescent organogelators, pyrene-containing poly(arylene ether
      sulfone)s, showed two fluorescence switching modes in different gelation
      solvents. The THF gel exhibited excimer emission due to dimerization of the
      pyrene groups. In contrast, excimer emission was quenched after gelation in MC
      because of stacking among the pyrene groups.

PMID- 23001300
TI  - Extra-gastrointestinal stromal tumor of the pelvic cavity: case report.
AB  - Extra-gastrointestinal stromal tumors (E-GISTs) not associated with the
      alimentary tract in the pelvic cavity are extremely rare. We treated a 49-year
      old Japanese man with such an E-GIST in the pelvic cavity who underwent an
      intrapelvic tumorectomy with a total prostatectomy and partial rectum resection.
      Gross examination of the specimen revealed an 8.1 * 5 * 4 cm white-grayish mass.
      Histological findings showed uniform spindle cells with scant atypia that formed
      interlacing bundles or whorl patterns. These neoplastic cells did not invade
      adjacent organs, including the gut. Immunohistochemical findings revealed that
      the neoplastic cells were positive for c-kit, CD34, and vimentin. Molecular
      analysis showed a c-kit mutation at exon 9 with duplication of Ala and Tyr. Our
      diagnosis was E-GIST, which belongs to the intermediate group of GIST. Following
      the operation, we administered imatinib mesylate for 6 months. After stopping for
      5 months, it was administered again for local recurrence. We are planning our
      future strategy for this case including surgical resection as necessary.

PMID- 23001302
TI  - Valley-spin blockade and spin resonance in carbon nanotubes.
AB  - The manipulation and readout of spin qubits in quantum dots have been
      successfully achieved using Pauli blockade, which forbids transitions between
      spin-triplet and spin-singlet states. Compared with spin qubits realized in III-V
      materials, group IV materials such as silicon and carbon are attractive for this
      application because of their low decoherence rates (nuclei with zero spins).
      However, valley degeneracies in the electronic band structure of these materials
      combined with Coulomb interactions reduce the energy difference between the
      blocked and unblocked states, significantly weakening the selection rules for
      Pauli blockade. Recent demonstrations of spin qubits in silicon devices have
      required strain and spatial confinement to lift the valley degeneracy. In carbon
      nanotubes, Pauli blockade can be observed by lifting valley degeneracy through
      disorder, but this makes the confinement potential difficult to control. To
      achieve Pauli blockade in low-disorder nanotubes, quantum dots have to be made
      ultrasmall, which is incompatible with conventional fabrication methods. Here, we
      exploit the bandgap of low-disorder nanotubes to demonstrate robust Pauli
      blockade based on both valley and spin selection rules. We use a novel stamping
      technique to create a bent nanotube, in which single-electron spin resonance is
      detected using the blockade. Our results indicate the feasibility of valley-spin
      qubits in carbon nanotubes.

PMID- 23001303
TI  - Single-molecule monitoring in living cells by use of fluorescence microscopy.
AB  - Monitoring single molecules in living cells is becoming a powerful tool for study
      of the location, dynamics, and kinetics of individual biomolecules in real time.
      In recent decades, several optical imaging techniques, for example epi
      fluorescence microscopy, total internal reflection fluorescence microscopy
      (TIRFM), confocal microscopy, quasi-TIRFM, and single-point edge excitation
      subdiffraction microscopy (SPEED), have been developed, and their capability of
      capturing single-molecule dynamics in living cells has been demonstrated. In this
      review, we briefly summarize recent advances in the use of these imaging
      techniques for monitoring single-molecules in living cells for a better
      understanding of important biological processes, and discuss future developments.

PMID- 23001304
TI  - The National Institute of Standards and Technology ambient level methane in air
      Standard Reference Material historical record.
AB  - The National Institute of Standards and Technology (NIST) has been certifying
      lots, or series, of Standard Reference Materials (SRMs) containing ambient level
      methane in air for over 40 years. The historical record contains six traditional
      series of SRM 1658 (1 MUmol mol(-1)), five of SRM 1660 (4 MUmol mol(-1)), and
      seven of SRM 1659 (10 MUmol mol(-1)) methane in air. All series of any one
      particular SRM can be linked to each other through the historical suites of
      gravimetric primary standard mixtures (PSMs) developed at NIST. One gas mixture
      cylinder from a series is chosen as the lot standard (LS), retained and held at
      NIST, and periodically compared to the PSMs to assure its stability. Recently, 6
      of the original 18 LS still in service in the Gas Metrology Group inventory, and
      cylinder samples held at NIST from 6 other SRM lots, were analyzed against a
      newly prepared suite of PSMs using cavity ring-down spectroscopy. Data were
      analyzed using a generalized least squares linear regression. The results
      indicate that, within the original 95% confidence intervals, the methane
      concentration has remained the same for all the SRM LS and lot samples. The
      current predicted concentrations of the LS and samples for SRMs 1659 and 1660 are
      within 0.002 to 0.051 MUmol mol(-1), or <=0.5%, relative of the original
      certificate value. SRM 1658 LS and samples are within 0.0001 to 0.0023 MUmol mol(
      1), or <=0.2% relative. These results illustrate the consistency, repeatability,
      and stability of these methane in air SRMs over the historical 35+-year record.
      It also demonstrates that the historical gravimetric primary methane in air
      suites have remained accurate and consistent over time.

PMID- 23001305
TI  - Speciation of Gd-based MRI contrast agents and potential products of
      transmetalation with iron ions or parenteral iron supplements.
AB  - The risk of transmetalation reactions between gadolinium complexes used as
      contrast agents for magnetic resonance imaging (MRI) and iron ions is examined
      under physiological conditions. A fast separation of gadopentetate (Gd-DTPA) and
      gadoterate (Gd-DOTA) and the respective Fe transmetalation products was
      accomplished by high-performance liquid chromatography. For detection, the LC
      system was coupled to an Orbitrap electrospray ionization mass spectrometer to
      achieve a detection limit as low as 50 nmol/L for Fe-DTPA. In vitro experiments
      revealed the formation of Fe-DTPA in blood plasma samples with Gd-DTPA and
      Fe(III) citrate. Analysis after different incubation times of the sample showed
      that the exchange of the metal ions is significantly dependent on time. If this
      reaction takes place in the body of MRI patients, this could explain why the
      disease nephrogenic systemic fibrosis (NSF) develops only after a longer
      retention of the linear Gd complex in the patient's body. Transmetalation either
      with endogenous Fe(II)/Fe(III) ions or with parenteral Fe supplements with Gd
      DTPA could not be proven under the applied conditions. The high stability of Gd
      DOTA is responsible that transmetalation between this macrocylic complex and
      neither of the Fe species was observed. These findings are important because NSF
      only develops after administration of Gd complexes with linear ligands. The
      results indicate that transmetalation reactions may be a trigger for the
      development of NSF, if free Fe(III) ions are accessible during a prolonged dwell
      time of Gd complexes with linear ligands in the patient's body.

PMID- 23001306
TI  - Dynorphin A 1-17 biotransformation in inflamed tissue, serum and trypsin solution
      analysed by liquid chromatography-tandem mass spectrometry.
AB  - Dynorphin A 1-17 (DYN A) is an endogenous neuropeptide that is of interest due to
      its diverse roles in analgesia, inflammation and addiction. Upon release, DYN A
      is subject to metabolism by a range of enzymes and its biotransformation is
      dependent on the site and environment into which it is released. In this study,
      we investigated the biotransformation of DYN A in rat inflamed tissue at pH 7.4
      and 5.5, in rat serum and in trypsin solution. DYN A-porcine was incubated at 37 
      degrees C in each matrix over a range of incubation periods. The resultant
      fragments were separated using a C4 column and detected by mass spectrometry
      using total ion current mode. Incubation of DYN A in trypsin solution and in rat
      serum resulted in 6 and 14 fragments, respectively. Incubation in inflamed rat
      paw tissue occasioned 21 fragments at pH 7.4 and 31 fragments at pH 5.5.
      Secondary breakdown of some larger primary fragments was also observed in this
      study.

PMID- 23001307
TI  - Dynamic processes and chemical composition of Lepidium sativum seeds determined
      by means of field-cycling NMR relaxometry and NMR spectroscopy.
AB  - Proton nuclear magnetic resonance (NMR) techniques, such as field-cycling
      relaxometry, wide-line NMR spectroscopy, and magic angle spinning NMR
      spectroscopy, were applied to study the seeds of cress, Lepidium sativum. Field
      cycling NMR relaxometry was used for the first time to investigate the properties
      of the whole molecular system of dry cress seeds. This method not only allowed
      the dynamics to be studied, but was also successful in the differentiation among
      the solid (i.e., carbohydrates, proteins, or fats forming a solid form of lipids)
      and liquid-like (oil compounds) components of the seeds. The (1)H NMR relaxation
      dispersion of oils was interpreted as a superposition of intramolecular and
      intermolecular contributions. The intramolecular part was described in terms of a
      Lorentzian spectral density function, whereas a log-Gaussian distribution of
      correlation times was applied for the intermolecular dipole-dipole contribution.
      The models applied led to very good agreement with the experimental data and
      demonstrate that the contribution of the intermolecular relaxation to the overall
      relaxation should not be disregarded, especially at low frequencies. A power-law
      frequency dependence of the proton relaxation dispersion was used for the
      interpretation of the solid components. From the analysis of the (1)H wide-line
      NMR spectra of the liquid-like component of hydrated cress seeds, we can conclude
      that the contribution of oil protons should always be taken into account when
      evaluating the spin-lattice relaxation times values or measuring the moisture and
      oil content. The application of (1)H magic angle spinning NMR significantly
      improves resolution in the liquid-like spectrum of seeds and allows the
      determination of the chemical composition of cress seeds.

PMID- 23001308
TI  - The unravelling of metabolic dysfunctions linked to metal-associated diseases by
      blue native polyacrylamide gel electrophoresis.
AB  - Gel electrophoresis is routinely used to separate and analyse macromolecules in
      biological systems. Although many of these electrophoretic techniques necessitate
      the denaturing of the analytes prior to their analysis, blue native
      polyacrylamide gel electrophoresis (BN-PAGE) permits the investigation of
      proteins/enzymes and their supramolecular structures such as the metabolon in
      native form. This attribute renders this analytical tool conducive to deciphering
      the metabolic perturbations invoked by metal toxicity. In this review, we
      elaborate on how BN-PAGE has led to the discovery of the dysfunctional metabolic
      pathways associated with disorders such as Alzheimer's disease, Parkinson's
      disease, and obesity that have been observed as a consequence of exposure to
      various metal toxicants.

PMID- 23001309
TI  - Phosphorylcholine-containing lipid molecular species profiling in biological
      tissue using a fast HPLC/QqQ-MS method.
AB  - A fast reversed-phase liquid chromatography-electrospray ionization triple
      quadrupole mass spectrometry method was developed for the molecular species
      profiling of glycerophosphocholine (GPC) and sphingomyelin (SM) in total lipid
      extracts. A two-stage mass spectrometry strategy was adopted to analyze in detail
      the composition of lipid molecular species. Precursor ion analysis was first
      conducted to obtain the preliminary composition profile of the phosphorylcholine
      containing lipid. The product ion spectra were sequentially acquired for each
      recorded signal to determine the molecular structure of the lipid. A total of 150
      GPCs and 12 SMs were identified in the fetal mouse lung with relative amounts
      ranging from 13.7% to less than 0.002% (normalizing by the total signal
      response). A column packed with core-shell particles was used to obtain excellent
      chromatographic separation with a shorter time demand in a conventional high
      performance liquid chromatography system. Considering the compromise between the
      chromatographic efficiency and the electrospray signal response, the optimization
      of the mobile phase improves the chromatographic plate number to approximately
      40,000 and the detection limits to less than 0.001 mg/L. The applicability of the
      method was validated through a study of chemically induced early lung maturation.
      The metabolic alteration in the fetal mouse lung was clearly reflected in the GPC
      and SM composition with several characteristics of the molecular structure that
      related to the character of the phospholipid layer upon the epithelial lining of
      alveoli and the relevant cell function. The results indicated that this
      analytical strategy is reliable for comprehensive molecular species profiling of
      GPC and SM and might be extended to the analysis of other phospholipids.

PMID- 23001310
TI  - Merging microfluidics and sonochemistry: towards greener and more efficient micro
      sono-reactors.
AB  - Microfluidics enable the manipulation of chemical reactions using very small
      amounts of fluid, in channels with dimensions of tens to hundreds of micrometers;
      so-called microstructured devices, from which the iconic image of chips emerges.
      The immediate attraction of microfluidics lies in its greenness: use of small
      quantities of reagents and solvents, and hence less waste, a precise control of
      reaction conditions, integration of functionality for process intensification,
      safer and often faster protocols, reliable scale-up, and possibility of
      performing multiphase reactions. Among the limitations found in microfluidics the
      facile formation of precipitating products should be highlighted, and in this
      context, the search for efficient mass and energy transfers is a must. Such
      limitations have been partially overcome with the aid of ultrasound in
      conventional flow systems, and can now be successfully used in microreactors,
      which provide new capabilities. Novel applications and a better understanding of
      the physical and chemical aspects of sonochemistry can certainly be achieved by
      combining microfluidics and ultrasound. We will review this nascent area of
      research, paying attention to the latest developments and showing future
      directions, which benefit both from the existing microfluidic technology and
      sonochemistry itself.

PMID- 23001311
TI  - Ready access to a branched Man5 oligosaccharide based on regioselective
      glycosylations of a mannose-tetraol with n-pentenyl orthoesters.
AB  - A branched Man(5) oligosaccharide has been synthesized by sequential
      regioselective glycosylations on a mannose-tetraol with n-pentenyl orthoester
      glycosyl-donors promoted by NIS/BF(3).Et(2)O, in CH(2)Cl(2). An extended n
      pentenyl chain was incorporated into the tetraol acceptor to facilitate (a) the
      solubility of the starting tetraol in CH(2)Cl(2), and (b) future manipulations at
      the reducing end of the Man(5) oligosaccharide.

PMID- 23001312
TI  - A role for the superior colliculus in the modulation of threat responsiveness in
      primates: toward the ontogenesis of the social brain.
AB  - Defense and social mechanisms in primates seem to share, at least in infancy,
      common neural substrata.Among these, recent research has implicated the primate
      superior colliculus (SC) on tasks involving visual detection and recognition of
      threatening stimuli, such as snakes and faces with emotional expressions. There
      is also evidence that both kinds of stimuli share specific characteristics and
      command special attention in the primate visual system. The present review
      focuses on the role of the SC in these seemingly overlapping functions.We present
      social behavioral data from capuchin monkeys in which the bilateral lesion of the
      SC induced a transitory impairment of social behaviors. The findings presented
      here are compared with previous studies, our own and others, on social behaviors
      and threat detection. We argue that, although the SC may participate in both
      systems,its role is more prominent in the detection/recognition of threat. Social
      interactions more likely depend on larger and more complex neural systems, where
      the SC may play a key role in early infancy. The implications of these recent
      findings are discussed under an evolutionary perspective.

PMID- 23001313
TI  - Differences between the aging process and the chronic cerebrovascular impairment
      of memory functioning: the emotional and cognitive interaction.
AB  - Three studies illustrate the relationship between memory, emotion, age, and
      chronic cerebro vascular disorders (CCVDs). In study A, emotion and age interact
      to produce secondary effects on memory functioning.In study B, emotion-related
      complaints are correlated with the cognition-related complaints only for high or
      low lev~ls of impairment For intermediate levels of impairment, the two
      components of subjective complaints are independent In study C, there is a
      relationship between aging and the pathological interference by CCVD on memory
      productivity; young healthy persons do better than aged healthy persons who do
      better than patients with vascular cognitive impairment (VCI). However,memory
      processing is different in terms of encoding and organization of stimuli. Young
      healthy subjects automatically use the semantic structure of the verbal
      stimuli,whereas the aged healthy persons do so only after a second learning
      session. Patients with VCI have lost this ability.They keep encoding and
      organizing items according to the serial effect, the common strategy
      spontaneously followed by everyone when presented with unstructured stimuli.
      These are examples of the complex relationships that characterize memory
      functioning and that should be taken into account when assessing memory when the
      role of the age factor, the emotional factor, and an eventual CCVD factor should
      be specifically identified.

PMID- 23001314
TI  - Emotional modulation of multiple memory systems: implications for the
      neurobiology of post-traumatic stress disorder.
AB  - In lower animals and humans, stress/anxiety can enhance dorsal striatal-dependent
      habit memory,at the expense of hippocampal-dependent cognitive memory. The
      present review considers the potential for this 'stress/anxiety-induced habit
      bias' to explain some aspects of post-traumatic stress disorder (PTSD). In
      rats,anxiety induced by peripheral or intra-amygdala infusions of anxiogenic
      drugs can enhance habit memory and impair cognitive memory. In tasks in which
      both habit and cognitive memory processes may provide a learned solution, stress
      and drug-induced anxiety favors the use of habit memory. The effect of stress and
      anxiety on the use of multiple memory systems in rats depends on the functional
      integrity of the basolateral amygdala. Thus,under robust emotional arousal,
      amygdala activation can modulate the relative use of memory systems in a manner
      that favors habit memory. We propose a similar mechanism may underlie the
      development and persistence of some PTSD symptoms. The traumatic memories of PTSD
      patients can be deficient in hippocampus-dependent contextual or autobiographical
      aspects, and enhanced in responding to trauma-related cues, which we suggest may
      reflect increased involvement of the dorsal striatum.We briefly consider the
      potential role of a stress/anxiety induced habit bias with regard to other
      psychopathologies,including obsessive-compulsive disorder and drug addiction.

PMID- 23001315
TI  - Interplay of amygdala and insular cortex during and after associative taste
      aversion memory formation.
AB  - The formation and storage of aversively motivated memories is based on plastic
      changes within the amygdala and other brain structures that are modulated by its
      activity. One of these structures is the insular cortex,which integrates
      environmental and interoceptive information such that memory traces can be
      efficient and rapidly stored. A great example of an aversively motivated learning
      is the taste aversion paradigm, which involves several changes at the cellular
      level of the amygdala and the insular cortex in order to be acquired and
      consolidated.So far, the interplay of these structures was described in terms of
      their participation during exposure to the stimuli to be associated; however,
      because of the cellular properties and interconnections between them, their
      functional interplay may go beyond the acquisition stage and the learning
      experience might trigger an ongoing engagement of amygdala-insular cortex
      reactivations in order to store the information.

PMID- 23001316
TI  - In vitro effects of three antidepressant drugs on plasma paraoxonase activity.
AB  - BACKGROUND: Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic
      metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to
      significantly decrease in depressed patients after antidepressant treatment
      instauration. Our aim was to investigate the in vitro inhibitory effects of three
      antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity.
      METHODS: Plasma from healthy volunteers was spiked with antidepressant drugs. The
      working solutions were then diluted with plasma to obtain concentrations that
      covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate
      after incubation at 37 degrees C for 2 h. RESULTS: Tricyclic antidepressants
      significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage
      for imipramine was 15.6% at 100 MUg/L after incubation for 1 h (131+/-1 vs. 155+/
      2 IU/L; p<0.01). At 350 MUg/L, the inhibition percentage for imipramine 19.2%
      after 1 h and 20.2% after 2 h. Amitriptyline was a stronger inhibitor: 26% after
      30 min at 125 MUg/L. At 250 MUg/L, the inhibition percentage for amitriptyline
      was 36.5% after 30 min (100+/-4 vs. 159+/-2 IU/L; p<0.01). CONCLUSIONS: The
      tested tricyclic antidepressants significantly inhibit PON1 activity in a
      concentration-dependent manner. Amitriptyline had a higher inhibition potency
      than imipramine.

PMID- 23001317
TI  - Rapid simultaneous genotyping of polymorphisms  in ADH1B and ALDH2 using high
      resolution  melting assay.

PMID- 23001318
TI  - Faecal calprotectin: comparative study of the Quantum Blue rapid test and an
      established ELISA method.
AB  - BACKGROUND: Faecal calprotectin is a non-invasive marker for neutrophilic
      intestinal inflammation. It can be used in the differential diagnosis between
      functional and organic bowel disease. Moreover, it correlates with endoscopic
      organic bowel disease activity. The objective of this study is to evaluate a
      recently launched quantitative immunochromatographic point-of-care test: Quantum
      Blue Calprotectin (Buhlmann Laboratories AG, Schonenbuch, Switzerland) in
      comparison to an established ELISA method (Buhlmann Laboratories AG). METHODS: We
      included 142 samples, either archived (-80 degrees C) faecal extracts or fresh
      routine samples. Both the normal range cartridges as well as the high range
      cartridge from the point-of-care test were used. The ELISA was compared with the
      point-of-care test and the optimal the point-of-care test cut-off values were
      searched for using Microsoft(r) Excel 2002 and MedCalc Software version 10.0.0.0
      (Mariakerke, Belgium). RESULTS: In the method comparison a determination
      coefficient (R2) of 0.89 was found. The Passing Bablok regression analysis showed
      a significant deviation from linearity (y=-40.8+1.0x). The use of a cut-off value
      of 30 MUg/g faeces and a grey zone of 30-110 MUg/g faeces resulted in the best
      agreement between the ELISA interpretation and the point-of-care test
      interpretation, with 89.4% (127/142) agreement and 10.6% (15/142) mismatches.
      CONCLUSIONS: We may conclude that the point-of-care test can serve as a reliable
      alternative to the time consuming ELISA in the differential diagnosis between
      functional and organic bowel disease. Furthermore, it seems to be reliable in the
      follow-up of inflammatory bowel disease patients.

PMID- 23001319
TI  - Cooperation experience in a multicentre study to define the upper limits in a
      normal population for the diagnostic assessment of the functional lupus
      anticoagulant assays.
AB  - BACKGROUND: Phospholipid-dependent coagulation tests for lupus anticoagulant (LA)
      are considered an important step for the diagnosis of anti-phospholipid syndrome;
      however, LA laboratory detection is difficult because of many variables. Five
      hospital laboratories, located in a North-Italy area and using the same method
      for LA testing, cooperated to standardise sample treatment and analytical
      procedure in order to define the upper values for LA negativity. METHODS: In
      total, 200 normal subjects (40 for each centre) were studied for six LA
      functional assays, using the same procedure, reagent lot and analyser type. The
      first tests done were LA screen and LA confirm assays, based on diluted Russell's
      Viper Venom Time, with low and high phospholipid content, respectively. The
      second tests performed were silica clotting time screen and confirm assays, based
      on activated partial thromboplastin time, with low and high phospholipid content,
      respectively. Finally, two mixing assays were executed for both screening assays,
      diluting patient sample with a pool prepared with plasma collected from the study
      population. RESULTS: Data analysis demonstrated a difference between centres for
      all assays when results were expressed in seconds; the difference disappeared
      when results are normalised with the local mean normal value of each centre and
      are expressed as a normalised ratio. The study population was normally
      distributed; so the value corresponding to 99th percentile was used as limit
      value for LA negativity. Values expressed as normalised ratio, for LA and silica
      clotting time screenings were 1.22 and 1.23, respectively. CONCLUSIONS: The study
      allowed us to define a uniform approach to LA testing and evaluation for
      laboratories employing the same methods.

PMID- 23001321
TI  - Retronasal olfaction in vegetable liking and disliking.
AB  - While previous research has suggested that bitterness is a key determinant of
      vegetable rejection, it is unknown what role odor may play. We therefore
      investigated the impact of retronasal odors on hedonic responses to 4 vegetables.
      Subjects (N = 132) tasted small samples with the nose open and closed and rated
      the degree of liking/disliking, as well as the perceived intensity of sweetness,
      bitterness, saltiness, and vegetable flavor. The subjects were classified as
      "likers" or "dislikers" of each vegetable. The degree to which "likers" liked and
      "dislikers" disliked the vegetables was significantly less in the nose-closed
      condition, indicating that retronasal odor was a significant driver of vegetable
      hedonics. In contrast, bitterness ratings for all 4 vegetables did not differ
      significantly between the groups. The perceived intensity of vegetable flavor
      also did not differ significantly between groups, implying that the quality of
      vegetable odors rather than their perceived intensity drove the hedonic ratings.
      In a follow-up experiment, returning subjects (N = 89) rated the degree of
      liking/disliking of the vegetable odors alone, which were presented retronasally.
      Liking/disliking of specific odors was positively correlated with that for the
      sampled vegetables across all stimuli (r = 0.32~0.57). Overall, these results
      suggest that retronasal odor plays an important role in vegetable
      liking/disliking.

PMID- 23001322
TI  - Microbase2.0: a generic framework for computationally intensive bioinformatics
      workflows in the cloud.
AB  - As bioinformatics datasets grow ever larger, and analyses become increasingly
      complex, there is a need for data handling infrastructures to keep pace with
      developing technology. One solution is to apply Grid and Cloud technologies to
      address the computational requirements of analysing high throughput datasets. We
      present an approach for writing new, or wrapping existing applications, and a
      reference implementation of a framework, Microbase2.0, for executing those
      applications using Grid and Cloud technologies. We used Microbase2.0 to develop
      an automated Cloud-based bioinformatics workflow executing simultaneously on two
      different Amazon EC2 data centres and the Newcastle University Condor Grid.
      Several CPU years' worth of computational work was performed by this system in
      less than two months. The workflow produced a detailed dataset characterising the
      cellular localisation of 3,021,490 proteins from 867 taxa, including bacteria,
      archaea and unicellular eukaryotes. Microbase2.0 is freely available from
      http://www.microbase.org.uk/.

PMID- 23001323
TI  - The description of protein internal motions aids selection of ligand binding
      poses by the INPHARMA method.
AB  - Protein internal motions influence observables of NMR experiments. The effect of
      internal motions occurring at the sub-nanosecond timescale can be described by
      NMR order parameters. Here, we report that the use of order parameters derived
      from Molecular Dynamics (MD) simulations of two holo-structures of Protein Kinase
      A increase the discrimination power of INPHARMA, an NMR based methodology that
      selects docked ligand orientations by maximizing the correlation of back
      calculated to experimental data. By including internal motion in the back
      calculation of the INPHARMA transfer, we obtain a more realistic description of
      the system, which better represents the experimental data. Furthermore, we
      propose a set of generic order parameters, derived from MD simulations of
      globular proteins, which can be used in the back-calculation of INPHARMA NOEs for
      any protein-ligand complex, thus by-passing the need of obtaining system-specific
      order parameters for new protein-ligand complexes.

PMID- 23001324
TI  - NMR characterization of the C-terminal tail of full-length RAGE in a membrane
      mimicking environment.
AB  - Targeting the receptor for the advanced glycation endproducts (RAGE) signalling
      has a potential for the prevention and treatment of several pathologies.
      Extracellular activation of RAGE triggers the interactions of the RAGE
      cytoplasmic tail with intracellular protein partners. Here the cytoplasmic tail
      of RAGE has been investigated by NMR as part of the full-length protein, in the
      presence of a membrane-mimicking environment. The isolated cytoplasmic tail has
      also been studied for comparison. The NMR spectra of the whole receptor show that
      some but not all residues belonging to the C-terminal region of the cytoplasmic
      tail have a large flexibility, while the membrane proximal region seems to be
      rigidly connected to the trans-membrane domain and ectodomains. The analysis
      indicates that the behavior of the cytoplasmic tail is strongly affected by its
      being part of the whole receptor. These results provide new insight towards the
      understanding of signal transduction by RAGE.

PMID- 23001326
TI  - Obituary for Arnold Sanderson 1933-2011: early pioneer in transplantation
      antigens research.

PMID- 23001325
TI  - Genetic characterization of two hill stream fish species Barilius bendelisis
      (Ham.1807) and Barilius barna (Ham.1822) using RAPD markers.
AB  - Genetic structure of four wild populations of two hill stream fishes Barilius
      bendelisis (Ham.1807) and B. barna (Ham. 1822) from Uttarakhand, India, was
      studied using RAPD markers. Eight selective primers provided distinct and
      consistent RAPD profiles in both the species, producing a total of 47 and 35
      scorable bands in B. bendelisis and B. barna respectively. The bands in the range
      666-4,830 bp were scored for consistent results. The RAPD profiles generated by
      all the eight primers revealed varying degrees of polymorphism (25.00-50.00 %).
      The average genetic diversity (h) was estimated as 0.1661 and 0.1606 among the
      four populations of B. bendelisis and B. barna respectively.

PMID- 23001327
TI  - Early histologic lesions and risk factors for recurrence of diabetic kidney
      disease after kidney transplantation.
AB  - BACKGROUND: Recurrence of diabetic kidney disease (DKD) after diabetic kidney
      transplantation has been reported. The aim of this study was to determine the
      early histologic lesions, focusing especially on abnormal glomerular
      angiogenesis, and clinical risk factors of recurrent DKD after kidney
      transplantation. METHODS: The authors studied 34 renal transplant recipients with
      diabetes and 30 without diabetes. All patients had undergone both baseline and
      posttransplant follow-up biopsies. Glomerular morphometric analyses of the
      mesangial area, the capillary number, and the capillary area were performed with
      a computer-assisted image analyzer, and glomerular basement membrane (GBM)
      thickness was evaluated by electron microscopy. The incidence of polar vasculosis
      as an angiogenic phenomenon was also evaluated. Clinical data including
      hemoglobin (Hb)A1c, blood pressure, urinary albumin excretion, and serum lipid
      profiles were compared with histologic parameters. RESULTS: Together with the
      increased glomerular mesangial area and GBM thickness, the glomerular capillary
      number and area and the incidence of polar vasculosis were significantly higher
      in patients with diabetes. Most of these alterations were significantly
      associated with the mean posttransplant HbA1c levels but not with blood pressure
      or lipid profiles. In the multiple regression analysis, HbA1c level remained
      significantly associated with these histologic parameters. CONCLUSIONS: Similar
      to mesangial expansion and GBM thickening, glomerular neovascularization
      represented by increased capillary number and area and glomerular polar
      vasculosis can occur as an early diabetic lesion in recurrent DKD. Posttransplant
      hyperglycemia is a significant risk factor predictive of the progression of
      recurrent DKD in kidney allografts.

PMID- 23001328
TI  - Malignant fibrous histiocytoma and fibrosarcoma of bone: a re-assessment in the
      light of currently employed morphological, immunohistochemical and molecular
      approaches.
AB  - Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) of bone are rare
      malignant tumours and contentious entities. Sixty seven cases labelled as bone
      MFH (57) and bone FS (10) were retrieved from five bone tumour referral centres
      and reviewed to determine whether recent advances allowed for reclassification
      and identification of histological subgroups with distinct clinical behaviour. A
      panel of immunostains was applied: smooth muscle actin, desmin, h-caldesmon,
      cytokeratin AE1-AE3, CD31, CD34, CD68, CD163, CD45, S100 and epithelial membrane
      antigen. Additional fluorescence in situ hybridisation and immunohistochemistry
      were performed whenever appropriate. All cases were reviewed by six bone and soft
      tissue pathologists and a consensus was reached. Follow-up for 43 patients
      (median 42 months, range 6-223 months) was available. Initial histological
      diagnosis was reformulated in 18 cases (26.8 %). Seven cases were reclassified as
      leiomyosarcoma, six as osteosarcoma, three as myxofibrosarcoma and one each as
      embryonal rhabdomyosarcoma and interdigitating dendritic cell sarcoma. One case
      showed a peculiar biphasic phenotype with epithelioid nests and myofibroblastic
      spindle cells. Among the remaining 48 cases, which met the WHO criteria for bone
      FS and bone MFH, we identified five subgroups. Seven cases were reclassified as
      undifferentiated pleomorphic sarcoma (UPS) and 11 as UPS with incomplete myogenic
      differentiation due to positivity for at least one myogenic marker. Six were
      reclassified as spindle cell sarcoma not otherwise specified. Among the remaining
      24 cases, we identified a further two recurrent morphologic patterns: eight cases
      demonstrated a myoepithelioma-like phenotype and 16 cases a myofibroblastic
      phenotype. One of the myoepithelioma-like cases harboured a EWSR1-NFATC2 fusion.
      It appears that bone MFH and bone FS represent at best exclusion diagnoses.

PMID- 23001329
TI  - Invasion of the inner and outer layers of the visceral pleura in pT1 size lung
      adenocarcinoma measuring <= 3 cm: correlation with malignant aggressiveness and
      prognosis.
AB  - Visceral pleural invasion (VPI) is defined as penetration by cancer cells of the
      elastic layer of the pleura. The purpose of this retrospective study was to
      compare the effect of invasion of the inner elastic layer of the pleura on
      survival to that of invasion of the outer elastic layer. One hundred twenty-four
      pT1 size lung adenocarcinomas were examined for visceral pleural invasion, which
      was classified into three types: no pleural invasion (NPI), invasion of the inner
      elastic layer only (IEL), and invasion of both inner and outer elastic layers
      (OEL). The relationship between the types of VPI and the prognosis was analyzed
      by univariate and multivariate analyses. Seventy-three (59 %) cancers showed NPI,
      while 51 cancers showed invasion of the pleura [(IEL) in 26 (21 %), OEL in 25 (20
      %)]. The 5-year survival was 81, 60, and 37 % for patients with NPI, IEL, and
      OEL, respectively. Survival was poorest in patients with OEL (P < 0.01). Invasion
      of the outer elastic layer was also significantly associated with lymph node
      metastasis and frequent lymphatic involvement, micropapillary pattern, higher
      stromal invasion grade, and presence of small cluster invasion within tumors.
      Univariate analysis showed a significant relationship between invasion of the
      outer elastic layer and poor prognosis. However, multivariate analysis identified
      lymph node metastasis as the most significant predictor of poor prognosis.
      Analysis of invasion of the inner and outer visceral pleura is important;
      invasion of the outer elastic layer correlates with poor prognosis in pT1 size
      lung adenocarcinomas.

PMID- 23001330
TI  - Towards a better integration of global health and biodiversity in the new
      sustainable development goals beyond Rio+20.
AB  - In June 2012, Brazil hosted Rio+20, the United Nations Conference on Sustainable
      Development (UNCSD) marking the 20th anniversary of the 1992 Earth Summit. The
      Rio+20 outcome document entitled The future we want provides general guidance to
      shape sustainable development policies, but fell short of providing legally
      binding agreements or pragmatic goals. Negotiators agreed to develop a process
      for the establishment of new Sustainable Development Goals (SDGs), building upon
      the Millennium Development Goals, and setting the foundation for the post-2015 UN
      development agenda. Our objective is to argue that discussions beyond Rio+20 and
      toward the adoption of SDGs offer a critical opportunity to re-assess the major
      challenges for global health and sustainable development. There is an urgent need
      to translate the general aspirations put forth by Rio+20 into concrete health
      outcomes and greater health equity. The way toward the post-2015 SDGs will likely
      be more effective if it highlights the full gamut of linkages between ecosystem
      processes, anthropogenic environmental changes (climate change, biodiversity
      loss, and land use), socio-economic changes, and global health. Negotiations
      beyond Rio+20 should strongly acknowledge the global health benefits of
      biodiversity protection and climate change mitigation and adaptation strategies,
      which reduce diseases of poverty and protect the health of the most vulnerable.
      We argue that health and ecosystems are inextricably linked to all development
      sectors and that health should remain a critical priority for the upcoming SDGs
      in the context of global environmental change.

PMID- 23001332
TI  - Selective and colorimetric fluoride anion chemosensor based on s-tetrazines.
AB  - s-Tetrazine and their derivatives are found to be a class of selective and
      colorimetric chemosensors for fluoride anions. The supramolecular interaction
      (anion-pi and charge/electron transfer) between fluoride ion and pi-electron
      deficient tetrazines receptor could facilitate the F(-)-tetrazines electron
      transfer (ET) event that generates tetrazine(-) radical anion. Accordingly, the
      color of its solution changed from red to green. Furthermore, the recognition of
      F(-) in DMSO is tolerant to water (DMSO-H(2)O = 9:1, v/v) and shows excellent
      selectivity towards other anions, especially H(2)PO(4)(-) and OAc(-).

PMID- 23001333
TI  - Photocarcinogenesis study of retinoic acid and retinyl palmitate [CAS Nos. 302-79
      4 (All-trans-retinoic acid) and 79-81-2 (All-trans-retinyl palmitate)] in SKH-1
      mice (Simulated Solar Light and Topical Application Study).
AB  - Topical retinoids, compounds that are metabolites, analogues, or derivatives of
      retinol and possess biological vitamin A activity, are among the most used
      adjunctive agents for the mitigation of fine wrinkles, mottled hyperpigmentation,
      and tactile roughness of photodamaged and chronically aged skin. Retinoic acid
      (RA) is the most active biological form of vitamin A and remains the medical
      treatment of choice for photoaged skin. Retinyl palmitate (RP) is the major
      storage form of vitamin A in the skin and, because RP is also the most stable of
      available vitamin A esters, it is readily incorporated into the oil phase of
      cosmetic creams or lotions. Therefore, the topical application of RP is a
      practical strategy for increasing the levels of vitamin A in the skin. Usual
      cosmetic product concentrations of RA range from 0.025% to 0.1% and those of RP
      range from 0.1% to 5%. With a maximum absorbance around 325 nm, RA and RP absorb
      both ultraviolet A and B radiation (UVA and UVB) in incident sunlight. A 1-year
      study was conducted in mice to determine whether RA and RP would alter the
      photocarcinogenicity of broad-UV spectrum light generated by xenon arc lamps,
      termed simulated solar light (SSL), or narrow spectrum UV light generated by UVA
      and UVB lamps.

PMID- 23001331
TI  - DFT investigations of phosphotriesters hydrolysis in aqueous solution: a model
      for DNA single strand scission induced by N-nitrosoureas.
AB  - DNA phosphotriester adducts are common alkylation products of DNA phosphodiester
      moiety induced by N-nitrosoureas. The 2-hydroxyethyl phosphotriester was reported
      to hydrolyze more rapidly than other alkyl phosphotriesters both in neutral and
      in alkaline conditions, which can cause DNA single strand scission. In this work,
      DFT calculations have been employed to map out the four lowest activation free
      energy profiles for neutral and alkaline hydrolysis of triethyl phosphate (TEP)
      and diethyl 2-hydroxyethyl phosphate (DEHEP). All the hydrolysis pathways were
      illuminated to be stepwise involving an acyclic or cyclic phosphorane
      intermediate for TEP or DEHEP, respectively. The rate-limiting step for all the
      hydrolysis reactions was found to be the formation of phosphorane intermediate,
      with the exception of DEHEP hydrolysis in alkaline conditions that the
      decomposition process turned out to be the rate-limiting step, owing to the
      extraordinary low formation barrier of cyclic phosphorane intermediate catalyzed
      by hydroxide. The rate-limiting barriers obtained for the four reactions are all
      consistent with the available experimental information concerning the
      corresponding hydrolysis reactions of phosphotriesters. Our calculations
      performed on the phosphate triesters hydrolysis predict that the lower formation
      barriers of cyclic phosphorane intermediates compared to its acyclic counter-part
      should be the dominant factor governing the hydrolysis rate enhancement of DEHEP
      relative to TEP both in neutral and in alkaline conditions.

PMID- 23001334
TI  - Suillus mycelia under elevated atmospheric CO2 support increased bacterial
      communities and scarce nifH gene activity in contrast to Hebeloma mycelia.
AB  - Bacterial communities associated with mycorrhizal roots are likely to respond to
      rising atmospheric CO(2) levels in terms of biomass, community composition and
      activity since they are supported by the carbon (C) flow outside the root tips,
      especially by exudation of low molecular weight organic compounds. We studied how
      general bacterial and diazotrophic communities associated with ectomycorrhizal
      (ECM) fungi respond to different belowground C supply conditions, mediated by
      elevated atmospheric CO(2) concentration under nitrogen (N) limited conditions.
      Microcosm systems were constructed using forest soil and Scots pine seedlings,
      which were either pre-inoculated with one of the ECM fungal species Hebeloma
      velutipes or Suillus variegatus, or non-inoculated. These fungal species differ
      in C allocation and exudation patterns. Seedlings were maintained under ambient
      (380 ppm) or elevated (700 ppm) CO(2) levels for 6 months. Quantitative
      polymerase chain reaction (PCR) showed a significant increase in 16S rRNA gene
      copy numbers for Suillus-inoculated microcosms under elevated CO(2) compared to
      ambient CO(2). The copy numbers of the nitrogenase reductase (nifH) gene were
      under the detection limit in all samples regardless the CO(2) treatments.
      Denaturing gradient gel electrophoresis analysis of PCR-amplified nifH genes
      revealed simple and consistent communities in all samples throughout the
      incubation period. A nested reverse transcription PCR approach revealed that
      expression of nifH genes were detected in some microcosms. Our findings suggest
      that the effect of mycorrhizal fungi on soil bacteria may vary depending on C
      supply and fungal species.

PMID- 23001335
TI  - Superhydrophobic and superoleophilic hybrid foam of graphene and carbon nanotube
      for selective removal of oils or organic solvents from the surface of water.
AB  - A monolithic 3D hybrid of graphene and carbon nanotube was synthesized by two
      step chemical vapor deposition. Owing to its superhydrophobic and superoleophilic
      properties, it can selectively remove oils and organic solvents from water with
      high absorption capacity and good recyclability.

PMID- 23001336
TI  - Application of quantitative PCR for the detection of microorganisms in water.
AB  - The occurrence of microorganisms in water due to contamination is a health risk
      and control thereof is a necessity. Conventional detection methods may be
      misleading and do not provide rapid results allowing for immediate action. The
      quantitative polymerase chain reaction (qPCR) method has proven to be an
      effective tool to detect and quantify microorganisms in water within a few hours.
      Quantitative PCR assays have recently been developed for the detection of
      specific adeno- and polyomaviruses, bacteria and protozoa in different water
      sources. The technique is highly sensitive and able to detect low numbers of
      microorganisms. Quantitative PCR can be applied for microbial source tracking in
      water sources, to determine the efficiency of water and wastewater treatment
      plants and act as a tool for risk assessment. Different qPCR assays exist
      depending on whether an internal control is used or whether measurements are
      taken at the end of the PCR reaction (end-point qPCR) or in the exponential phase
      (real-time qPCR). Fluorescent probes are used in the PCR reaction to hybridise
      within the target sequence to generate a signal and, together with specialised
      systems, quantify the amount of PCR product. Quantitative reverse transcription
      polymerase chain reaction (q-RT-PCR) is a more sensitive technique that detects
      low copy number RNA and can be applied to detect, e.g. enteric viruses and viable
      microorganisms in water, and measure specific gene expression. There is, however,
      a need to standardise qPCR protocols if this technique is to be used as an
      analytical diagnostic tool for routine monitoring. This review focuses on the
      application of qPCR in the detection of microorganisms in water.

PMID- 23001337
TI  - Design, implementation and evaluation of an independent real-time safety layer
      for medical robotic systems using a force-torque-acceleration (FTA) sensor.
AB  - PURPOSE: Most medical robotic systems require direct interaction or contact with
      the robot. Force-Torque (FT) sensors can easily be mounted to the robot to
      control the contact pressure. However, evaluation is often done in software,
      which leads to latencies. METHODS: To overcome that, we developed an independent
      safety system, named FTA sensor, which is based on an FT sensor and an
      accelerometer. An embedded system (ES) runs a real-time monitoring system for
      continuously checking of the readings. In case of a collision or error, it
      instantaneously stops the robot via the robot's external emergency stop. RESULTS:
      We found that the ES implementing the FTA sensor has a maximum latency of
      [Formula: see text] ms to trigger the robot's emergency stop. For the standard
      settings in the application of robotized transcranial magnetic stimulation, the
      robot will stop after at most 4 mm. CONCLUSION: Therefore, it works as an
      independent safety layer preventing patient and/or operator from serious harm.

PMID- 23001338
TI  - Fine mapping and characterization of BPH27, a brown planthopper resistance gene
      from wild rice (Oryza rufipogon Griff.).
AB  - The brown planthopper (Nilaparvata lugens Stal; BPH) is one of the most serious
      rice pests worldwide. Growing resistant varieties is the most effective way to
      manage this insect, and wild rice species are a valuable source of resistance
      genes for developing resistant cultivars. BPH27 derived from an accession of
      Guangxi wild rice, Oryza rufipogon Griff. (Accession no. 2183, hereafter named
      GX2183), was primarily mapped to a 17-cM region on the long arm of the chromosome
      four. In this study, fine mapping of BPH27 was conducted using two BC(1)F(2)
      populations derived from introgression lines of GX2183. Insect resistance was
      evaluated in the BC(1)F(2) populations with 6,010 individual offsprings, and 346
      resistance extremes were obtained and employed for fine mapping of BPH27. High
      resolution linkage analysis defined the BPH27 locus to an 86.3-kb region in
      Nipponbare. Regarding the sequence information of rice cultivars, Nipponbare and
      93-11, all predicted open reading frames (ORFs) in the fine-mapping region have
      been annotated as 11 types of proteins, and three ORFs encode disease-related
      proteins. Moreover, the average BPH numbers showed significant differences in 96
      120 h after release in comparisons between the preliminary near-isogenic lines
      (pre-NILs, lines harboring resistance genes) and BaiR54. BPH growth and
      development were inhibited and survival rates were lower in the pre-NIL plants
      compared with the recurrent parent BaiR54. The pre-NIL exhibited 50.7% reductions
      in population growth rates (PGR) compared to BaiR54. The new development in fine
      mapping of BPH27 will facilitate the efforts to clone this important resistant
      gene and to use it in BPH-resistance rice breeding.

PMID- 23001339
TI  - Generation of fluorescent silver nanoscale particles in reverse micelles using
      gamma irradiation.
AB  - Reverse micelles (RMs) containing aqueous solutions of Ag(+) ions in their core
      produce fluorescent Ag species, upon exposure to gamma irradiation. A two-phase
      liquid system is used for RM formation. The RMs can be employed in novel gamma
      radiation detectors with appearance of fluorescence indicating that radiation was
      once present.

PMID- 23001340
TI  - Invited commentary: efficacy of popliteal block in postoperative pain control
      after ankle fracture fixation: a prospective randomized study.

PMID- 23001342
TI  - Immunotherapy: Isolation of T(CM) cells for tumour immunotherapy.

PMID- 23001343
TI  - Therapeutics: PI3K-PARP combination.

PMID- 23001350
TI  - A covalently reactive group-modified peptide that specifically reacts with
      lysine16 in amyloid beta.
AB  - Lys16 is present in the core region of the amyloid beta (Abeta) self-assembly in
      Alzheimer's disease. Here we report that the P9-NCS peptide can covalently react
      with Lys16 and inhibit Abeta neurotoxic fibrillization. Moreover P9-NCS has high
      selectivity and it cannot react with amylin, insulin, fetal bovine serum, Q11 and
      MUC1 peptide.

PMID- 23001351
TI  - Predicting proximal femur rotation by morphological analyses using translucent 3
      dimensional computed tomography.
AB  - BACKGROUND: Predicting rotation of proximal femur in femur fracture surgeries is
      important to prevent malrotation. OBJECTIVE: We aimed to prevent malrotation by
      developing a simple guideline that enables the prediction of proximal femur
      rotation using translucent 3-dimensional computed tomography (3D CT). DESIGN:
      Retrospective. SETTING: One tertiary general hospital in the Republic of Korea.
      PATIENTS: Thirty-six subjects who underwent CT angiographies for vascular
      evaluation. INTERVENTION: Translucent 3D CT images were created from the CT data.
      MAIN OUTCOME MEASURE: Morphologic ratios of the great trochanter (GT) and lesser
      trochanter (LT) with the hip center as a basic point were measured at neutral
      position and at 5 degrees , 10 degrees , 15 degrees , 20 degrees , 25 degrees ,
      and 30 degrees  of internal rotation (IR) and external rotation (ER). The
      rotation angles at which the GT ratio becomes 0.5 and 0.33 and the rotation
      angles at which the LT ratio becomes 0.0 and 1.0 were determined to serve as
      guide angles. RESULTS: Both the proportion of GT and LT compared with proximal
      femur with hip center as a reference (GT and LT ratio) gradually increased in the
      shift from IR to ER. At a neutral position, the GT and LT ratios were
      approximately 0.4 and 0.5, respectively. At 10 degrees -15 degrees  of ER, the
      approximate GT and LT ratios were 0.5 and 1.0, respectively. At 30 degrees  of
      ER, the GT ratio exceeded 0.6, and the LT ratio exceeded 1.0. Between 10 degrees 
      and 15 degrees  of IR, the GT ratio decreased to approximately 0.33 and the LT
      ratio decreased to 0.0, which indicated that the LT was invisible. CONCLUSIONS:
      We suggested practical values which might be useful as a reference in the
      operating room practically and hope that our findings would be helpful to prevent
      malrotation while performing proximal femur or femur shaft surgeries.

PMID- 23001348
TI  - Mitochondria and cancer.
AB  - Contrary to conventional wisdom, functional mitochondria are essential for the
      cancer cell. Although mutations in mitochondrial genes are common in cancer
      cells, they do not inactivate mitochondrial energy metabolism but rather alter
      the mitochondrial bioenergetic and biosynthetic state. These states communicate
      with the nucleus through mitochondrial 'retrograde signalling' to modulate signal
      transduction pathways, transcriptional circuits and chromatin structure to meet
      the perceived mitochondrial and nuclear requirements of the cancer cell. Cancer
      cells then reprogramme adjacent stromal cells to optimize the cancer cell
      environment. These alterations activate out-of-context programmes that are
      important in development, stress response, wound healing and nutritional status.

PMID- 23001352
TI  - Determination of orientational isomerism in rhodium(II) metallopeptides by pyrene
      fluorescence.
AB  - Rhodium(II) metallopeptides display useful secondary structure, self-assembly,
      and catalytic activity. The bis-peptide complexes exhibit subtle orientational
      isomerism that affects function, but is challenging to characterize. We report
      that pyrene excimer fluorescence measurements provide a conclusive proof of
      isomeric structure.

PMID- 23001353
TI  - Early corticosteroid withdrawal in recipients of renal allografts:  a single
      center report of ethnically diverse recipients and recipients of marginal
      deceased-donor kidneys.
AB  - BACKGROUND: Candidacy for kidney transplantation is being progressively
      liberalized, and the safety and efficacy of early withdrawal of corticosteroids
      in high-risk patients have not been fully characterized. METHODS: We analyzed the
      safety and efficacy of an early corticosteroid withdrawal regimen of rabbit
      antithymocyte globulin induction, tacrolimus, mycophenolate mofetil, and steroid
      withdrawal by day 5 after transplantation in our study cohort of 634 kidney
      transplant recipients that included 27% African American and 18% Hispanic
      recipients. Fifty-five percent of the recipients were recipients of deceased
      donor kidneys, and 46% of deceased-donor kidneys were kidneys from expanded
      criteria donors. RESULTS: Kaplan-Meier patient survival at 1, 3, and 5 years
      after transplantation was 98.6%, 94.6%, and 90.2%, and death-censored graft
      survival was 96.2%, 91.9%, and 87.6%, respectively. During a mean follow-up of 57
      months, 89.3% of patients remained off of corticosteroids, and the incidence of
      acute rejection including subclinical rejection identified by protocol biopsy was
      12.0%. Multivariable analysis identified age older than 60 years as protective
      against (P=0.01) and the African American ethnicity as a risk factor for (P=0.03)
      rejection. Delayed graft function (P<0.0001), rejection (P<0.0001), and
      transplant panel reactive antibody 20% or more (P=0.03) were risk factors for
      graft loss. Opportunistic infections included viral in 15.3%, fungal in 1.6%, and
      parasitic in 0.6% of the patients. Posttransplantation malignancy occurred in
      9.1% of patients. CONCLUSIONS: An early corticosteroid withdrawal regimen of
      rabbit antithymocyte globulin induction, tacrolimus, and mycophenolate mofetil is
      associated with excellent patient and kidney graft survival in an ethnically
      diverse population with risk factors for poor outcomes.

PMID- 23001349
TI  - Controlling escape from angiogenesis inhibitors.
AB  - Selective inhibition of vascular endothelial growth factor (VEGF) increases the
      efficacy of chemotherapy and has beneficial effects on multiple advanced cancers,
      but response is often limited and the disease eventually progresses. Changes in
      the tumour microenvironment--hypoxia among them--that result from vascular
      pruning, suppressed angiogenesis and other consequences of VEGF inhibition can
      promote escape and tumour progression. New therapeutic approaches that target
      pathways that are involved in the escape mechanisms add the benefits of blocking
      tumour progression to those of slowing tumour growth by inhibiting angiogenesis.

PMID- 23001354
TI  - Increased infection rate after preemptive rituximab treatment for Epstein-Barr
      virus reactivation after allogeneic hematopoietic stem-cell transplantation.
AB  - BACKGROUND: Preemptive rituximab (R) treatment decreases the incidence of Epstein
      Barr virus (EBV) posttransplantation lymphoproliferative disease, but the extent
      of immune deficiency related to R in patients who received allogeneic
      hematopoietic stem-cell transplantation is unclear. The aim of our study was to
      evaluate the incidence of late infections and immune reconstitution after
      preemptive R treatment of EBV infection. METHODS: Seventy-eight patients
      receiving preemptive R between January 2005 and January 2010 were studied. Fifty
      two of them could be matched with controls (not receiving R) according to
      administration of antithymoglobulin, stem-cell source and donor type, age and
      grade of acute graft-versus-host disease. RESULTS: Among the 78 patients with EBV
      reactivation treated with R, the 36-month cumulative incidence of bacterial,
      viral, and fungal infections was 64%, 59%, and 23%, respectively. When compared
      with controls, bacterial infection incidence was significantly higher in R
      patients (55% vs. 35%), and a slower reconstitution of B cells was observed. R
      patients had modest but not significantly higher nonrelapse mortality (35% vs.
      15%) than controls. CONCLUSION: R has dramatically decreased risks of
      posttransplantation lymphoproliferative disease but is followed by a prolonged
      and profound B-cell deficiency associated with an excess risk of bacterial
      infection and higher mortality. R should be given with caution, and
      immunoglobulin replacement should be provided to limit these excess risks.

PMID- 23001355
TI  - Antibody alone is not a stimulator of exocytosis of Weibel-Palade bodies from
      human endothelial cells.
AB  - BACKGROUND: The mechanisms of antibody-mediated damage to allografts are not well
      understood. We have examined the effect of antibodies to human leukocyte antigens
      on secretion of von Willebrand factor (vWF) from endothelial cells (ECs).
      METHODS: The effect of monoclonal antibodies (W6/32, L2, and L243), in the
      presence and absence of sublytic concentrations of complement, on the release of
      vWF from Weibel-Palade bodies (WPBs) in human umbilical vein ECs (HUVECs), human
      aortic ECs (HAECs), and human heart microvascular ECs (HHMECs) was investigated
      using biochemical and live-cell imaging. Fura-2-loaded ECs expressing the WPB
      marker proregion-enhanced green fluorescence protein were imaged simultaneously
      for intracellular Ca(2+) changes ([Ca(2+)](i)) and WPB exocytosis. RESULTS:
      Stimulation of ECs with 1- or 10-ug/mL W6/32, L2, or L243 did not evoke
      significant vWF release above control IgG. In live-cell imaging studies, exposure
      of proregion-enhanced green fluorescence protein-expressing HAECs to physiologic
      saline, 10-ug/mL U9F4, or W6/32 alone for 5 to 10 min induced irregular
      (Ca(2+))(i)? spiking but no WPB exocytosis. Histamine-evoked WPB exocytosis was
      not changed by preexposure of HAECs to physiologic saline, U9F4, or W6/32.
      Stimulation of HUVECs with sublytic complement concentrations evoked WPB
      exocytosis; however, the addition of W6/32 did not change the amount of vWF
      released. CONCLUSION: Antibodies to human leukocyte antigen class I or II do not
      elicit significant WPB exocytosis or vWF secretion from ECs in the absence of
      exogenous complement.

PMID- 23001357
TI  - The metabolism of neurons and astrocytes through mathematical models.
AB  - Mathematical modeling of the energy metabolism of brain cells plays a central
      role in understanding data collected with different imaging modalities, and in
      making predictions based on them. During the last decade, several sophisticated
      brain metabolism models have appeared. Unfortunately, the picture of the
      metabolic details that emerges from them is far from coherent: while each model
      has its justification and is in agreement with some experimental data, some of
      the predictions of different models can diverge from each other significantly. In
      this article, we review some of the recent published models, emphasizing
      similarities and differences between them to understand where the differences in
      predictions stem from. In that context we present a probabilistic approach, which
      rather than assigning fixed values to the model parameters, regard them as random
      variables whose distributions are inferred on in the light of stoichiometric
      information and different observations. The probabilistic approach reveals how
      much intrinsic variability a metabolic system may contain, which in turn may be a
      valid explanation of the different findings.

PMID- 23001356
TI  - Plasma microRNA biomarkers for detection of mild cognitive impairment.
AB  - Early stages of many neurodegenerative diseases, such as Alzheimer's disease,
      vascular and frontotemporal dementia, and Parkinson's disease, are frequently
      associated with Mild Cognitive Impairment (MCI). A minimally invasive screening
      test for early detection of MCI may be used to select optimal patient groups in
      clinical trials, to monitor disease progression and response to treatment, and to
      better plan patient clinical care. Here, we examined the feasibility of using
      pairs of brain-enriched plasma microRNA (miRNA), at least one of which is
      enriched in synapses and neurites, as biomarkers that could differentiate
      patients with MCI from age-matched controls. The identified biomarker pairs fall
      into two sets: the "miR-132 family" (miR-128/miR-491-5p, miR-132/miR-491-5p and
      mir-874/miR-491-5p) and the "miR-134 family" (miR-134/miR-370, miR-323-3p/miR-370
      and miR-382/miR-370). The area under the Receiver-Operating Characteristic curve
      for the differentiation of MCI from controls using these biomarker pairs is 0.91
      0.95, with sensitivity and specificity at 79%-100% (miR-132 family) and 79%-95%
      (miR-134 family), and p<0.001. In a separate longitudinal study, the identified
      miRNA biomarker pairs successfully detected MCI in majority of patients at
      asymptomatic stage 1-5 years prior to clinical diagnosis. The reported biomarker
      pairs also appear useful for detecting age-related brain changes. Further testing
      in a larger study is necessary for validation of these results.

PMID- 23001358
TI  - Side by side treadmill walking with intentionally desynchronized gait.
AB  - Humans demonstrate an innate desire to synchronize stepping when walking side by
      side. This behavior requires modification of each person's gait, which may
      increase for pairings with very different walking patterns. The purpose of this
      study was to compare locomotor behavior for conditions in which partners
      exhibited similar and substantially different walking patterns. Twenty-six
      unimpaired subjects walked on a motorized treadmill at their preferred walking
      speed for three trials: by themselves (SOLO), next to someone on an adjacent
      treadmill (PAIRED), and next to someone who purposely avoided synchronization by
      altering stride times and/or lengths (DeSYNC). Means, coefficients of variance,
      approximate entropy (ApEn), rate of autocorrelation decay (alpha), and estimates
      of maximal Lyapunov exponents (lambda*) were calculated for several dependent
      variables taken from sagittal plane kinematic data. Few differences in behavior
      were noted when the PAIRED condition was compared to the SOLO condition. However,
      the DeSYNC condition resulted in several alterations in ApEn, alpha, and lambda*.
      These results suggest that greater differences in walking pattern between
      partners will facilitate greater modification to an individual's gait. Additional
      study of side by side walking may hold implications for understanding the control
      of gait in humans and may have application in a clinical setting. 

PMID- 23001360
TI  - Multiscale systems biology: a special issue devoted to understanding biology and
      medicine across multiple scales.

PMID- 23001359
TI  - High content evaluation of shear dependent platelet function in a microfluidic
      flow assay.
AB  - The high blood volume requirements and low throughput of conventional flow assays
      for measuring platelet function are unsuitable for drug screening and clinical
      applications. In this study, we describe a microfluidic flow assay that uses 50
      MUL of whole blood to measure platelet function on ~300 micropatterned spots of
      collagen over a range of physiologic shear rates (50-920 s(-1)). Patterning of
      collagen thin films (CTF) was achieved using a novel hydrated microcontact
      stamping method. CTF spots of 20, 50, and 100 MUm were defined on glass
      substrates and consisted of a dense mat of nanoscale collagen fibers (3.74 +/-
      0.75 nm). We found that a spot size of greater than 20 MUm was necessary to
      support platelet adhesion under flow, suggesting a threshold injury size is
      necessary for stable platelet adhesion. Integrating 50 MUm CTF microspots into a
      multishear microfluidic device yielded a high content assay from which we
      extracted platelet accumulation metrics (lag time, growth rate, total
      accumulation) on the spots using Hoffman modulation contrast microscopy. This
      method has potential broad application in identifying platelet function defects
      and screening, monitoring, and dosing antiplatelet agents.

PMID- 23001361
TI  - Breast cancer subtype affects patterns of failure of brain metastases after
      treatment with stereotactic radiosurgery.
AB  - We investigate the variance in patterns of failure after Gamma KnifeTM
      radiosurgery (GKRS) for patients with brain metastases based on the subtype of
      the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were
      treated with GKRS for brain metastases. Tumor subtypes were approximated based on
      hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B
      (HR+/HER2(-)); HER2 (HER2+/HR(-)); Luminal HER2 (HR+/HER2+), Basal (HR(-)/HER2(
      )), and then based on HER2 status alone. The median follow-up period was 54
      months. Kaplan-Meier method was used to estimate survival times. Multivariable
      analysis was performed using Cox regression models. Median number of lesions
      treated was two (range 1-15) with a median dose of 20 Gy (range 9-24 Gy). Median
      overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2,
      and Luminal HER2, respectively (p = 0.001), and was 17 and 8 months for HER2+ and
      HER(-) patients, respectively (p < 0.001). Breast cancer subtype did not predict
      time to local failure (p = 0.554), but did predict distant brain failure rate
      (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2
      respectively, p < 0.001). An increased proportion of HER2+ patients experienced
      neurologic death (46 vs 31 %, p = 0.066). Multivariate analysis revealed that
      HER2+ patients (p = 0.007) independently predicted for improved survival. Women
      with basal subtype have high rates of distant brain failure and worsened
      survival. Our data suggest that differences in biologic behavior of brain
      metastasis occur across breast cancer subtypes.

PMID- 23001362
TI  - Mechanisms of invasion and persistence of infectious agents.

PMID- 23001363
TI  - Ion disturbance and clustering in the NaCl water solutions.
AB  - Ion clustering and the solvation properties in the NaCl solutions are explored by
      molecular dynamics simulations with several popular force fields. The existence
      of ions has a negligible disturbance to the hydrogen bond structures and
      rotational mobility of water beyond the first ion solvation shells, which is
      suggested by the local hydrogen bond structures and the rotation times of water.
      The potential of mean force (PMF) of ion pair in the dilute solution presents a
      consistent view with the populations of ion clusters in the electrolyte
      solutions. The aggregation level of ions is sensitive to the force field used in
      the simulations. The ion-ion interaction potential plays an important role in the
      forming of the contact ion pair. The entropy of water increases as the ion pair
      approaches each other and the association of ion pair is driven by the increment
      of water entropy according to the results from the selected force fields. The
      kinetic transition from the single solvent separated state to the contact ion
      pair is controlled by the enthalpy loss of solution.

PMID- 23001364
TI  - Tetrahydrofuran ring opening and related reactions with an N-heterocyclic carbene
      boryl trifluoromethanesulfonate.
AB  - Reaction of the triflate group in dipp-Imd-BH(2)OTf with nucleophiles generally
      occurs by direct substitution to give products dipp-Imd-BH(2)Nu. In contrast,
      reaction of this boryl triflate with aryloxides (ArO(-)) in THF resulted in
      insertion of THF with ring opening in between the NHC-boryl electrophile and the
      aryloxide to give products dipp-Imd-BH(2)O(CH(2))(4)OAr. The incorporation of THF
      was observed with other nucleophiles such as ethylthiolate and
      trimethylsilanolate whose conjugate acids have pK(a) values similar to that of
      phenol. The cleavage of ethyl acetate and oxetane is reported as well. A possible
      mechanism is proposed.

PMID- 23001365
TI  - Clinical manifestations of abdominal wall endometriosis: a single center
      experience.
AB  - OBJECTIVE: This study aimed to investigate the clinical manifestations and
      treatment outcomes of abdominal wall endometriosis (AWE). MATERIALS AND METHODS:
      Patients diagnosed with AWE at the Gil Medical Center from January 2002 to
      September 2010 were retrospectively reviewed. RESULTS: Thirty-seven women were
      treated for AWE during the study period. Median age was 34 (range 24-45) years,
      and median duration from last pelvic surgery until symptom onset was 30 (range 6
      96) months. The most common initial symptom was a palpable mass (36, 97.2 %),
      followed by cyclic or spontaneous pain (21, 56.8 %). Preoperative diagnoses were
      accurate in 20 of 29 patients (68.9 %), who underwent a preoperative imaging
      study. The accuracy of abdominal US was 80 % (12/15). All patients underwent wide
      excision, and the median tumor size was 3.5 (range 1.0-10.0) cm. One patient
      experienced recurrence at 34 months postoperatively. CONCLUSIONS: Physicians
      should be aware of AWE in any woman presenting with palpable mass and/or pain at
      the abdominal wall, especially after pelvic surgery. Adequate preoperative
      estimation and wide excision might be essential for the treatment of AWE.

PMID- 23001366
TI  - Acceptable predictive accuracy of histopathology results by colposcopy done by
      Gynecology residents using Reid index.
AB  - OBJECTIVE: The aim of this study was to determine the strength of the correlation
      between colposcopic impression according to Reid colposcopic index (RCI) done by
      Gynecology residents and biopsy histology in a university hospital. METHODS:
      Colposcopy was performed on 260 women. According to RCI, the scores zero, one, or
      two were given to each of four standardized colposcopy patterns (acid staining,
      iodide staining, margin of lesion, and vascular pattern) and the total score was
      calculated. In those with multiple lesions, the patterns with the highest score
      were considered. Then the biopsy was obtained from the lesion and put in formalin
      for pathological evaluation. RESULTS: There was a statistically significant
      association between colposcopy findings and histopathology findings and the score
      was increased as parallel as malignancy grade (r = 0.680, P < 0.05). The highest
      sensitivity and specificity for diagnosis of each CIN also were related to
      staining with acetic acid. For high-grade CIN lesions, the highest specificity
      was related to staining with acetic acid, but the sensitivity was equal for four
      findings. CONCLUSION: Colposcopy using RCI yields a good correlation with
      histology results. It also showed that colposcopy done by Gynecology residents
      using RCI is a feasible and acceptable cervical cancer screening method in a
      university hospital.

PMID- 23001367
TI  - A novel modification to manual rotation of the foetal head: making the manoeuvre
      safer.

PMID- 23001368
TI  - Laparoscopic repair of vaginal vault prolapse by lateral suspension with mesh.
AB  - BACKGROUND: To evaluate the long-term outcomes of laparoscopic lateral suspension
      using mesh reinforcement for symptomatic posthysterectomy vaginal vault prolapse.
      MATERIALS AND METHODS: We analyzed in a prospective cohort study all the women
      treated by laparoscopic lateral suspension with mesh for symptomatic vaginal
      vault prolapse between January 2004 and September 2010. In this procedure, the
      mesh is laterally suspended to the abdominal wall, posterior to the anterior
      superior iliac spine. We performed systematic follow-up examinations at 4 weeks,
      6 months and yearly postoperatively. Clinical evaluation of pelvic organ support
      was assessed by the pelvic organ prolapse quantification (POP-Q) grading system.
      Main outcome measures were recurrence rate, reoperation rate for symptomatic
      recurrence or de novo prolapse, mesh erosion rate, reoperation rate for mesh
      erosion, total reoperation rate. OBSERVATIONS AND RESULTS: Of the 73 patients
      seen at a mean 17.5 months follow-up, recurrent vaginal vault prolapse was
      registered in only one woman (success rate of 98.6 %). When considering all
      vaginal sites, we observed a total of 13 patients with recurrent or de novo
      prolapse (17.8 %). The non-previously treated posterior compartment was involved
      in eight cases (new appearance rate of 11 %). Of these 13 women, only 6 were
      symptomatic, requiring surgical management (reoperation rate for genital prolapse
      of 8.2 %). Four patients presented with mesh erosion into the vagina (5.5 %). Two
      required partial vaginal excision of the mesh in the operating room (2.7 %).
      There were no mesh-related infections. The total reoperation rate was 11 %.
      CONCLUSION: Laparoscopic lateral suspension with mesh interposition is a safe and
      effective technique for the treatment of vaginal vault prolapse. This approach
      represents an alternative procedure to the laparoscopic sacrocolpopexy.

PMID- 23001369
TI  - Electrocorticographic (ECoG) correlates of human arm movements.
AB  - Invasive and non-invasive brain-computer interface (BCI) studies have long
      focused on the motor cortex for kinematic control of artificial devices. Most of
      these studies have used single-neuron recordings or electroencephalography (EEG).
      Electrocorticography (ECoG) is a relatively new recording modality in BCI
      research that has primarily been built on successes in EEG recordings. We built
      on prior experiments related to single-neuron recording and quantitatively
      compare the extent to which different brain regions reflect kinematic tuning
      parameters of hand speed, direction, and velocity in both a reaching and tracing
      task in humans. Hand and arm movement experiments using ECoG have shown positive
      results before, but the tasks were not designed to tease out which kinematics are
      encoded. In non-human primates, the relationships among these kinematics have
      been more carefully documented, and we sought to begin elucidating that
      relationship in humans using ECoG. The largest modulation in ECoG activity for
      direction, speed, and velocity representation was found in the primary motor
      cortex. We also found consistent cosine tuning across both tasks, to hand
      direction and velocity in the high gamma band (70-160 Hz). Thus, the results of
      this study clarify the neural substrates involved in encoding aspects of motor
      preparation and execution and confirm the important role of the motor cortex in
      BCI applications.

PMID- 23001370
TI  - Mind the step: complementary effects of an implicit task on eye and head
      movements in real-life gaze allocation.
AB  - Gaze in real-world scenarios is controlled by a huge variety of parameters, such
      as stimulus features, instructions or context, all of which have been studied
      systematically in laboratory studies. It is, however, unclear how these results
      transfer to real-world situations, when participants are largely unconstrained in
      their behavior. Here we measure eye and head orientation and gaze in two
      conditions, in which we ask participants to negotiate paths in a real-world
      outdoor environment. The implicit task set is varied by using paths of different
      irregularity: In one condition, the path consists of irregularly placed steps,
      and in the other condition, a cobbled road is used. With both paths located
      adjacently, the visual environment (i.e., context and features) for both
      conditions is virtually identical, as is the instruction. We show that terrain
      regularity causes differences in head orientation and gaze behavior, specifically
      in the vertical direction. Participants direct head and eyes lower when terrain
      irregularity increases. While head orientation is not affected otherwise,
      vertical spread of eye-in-head orientation also increases significantly for more
      irregular terrain. This is accompanied by altered patterns of eye movements,
      which compensate for the lower average gaze to still inspect the visual
      environment. Our results quantify the importance of implicit task demands for
      gaze allocation in the real world, and imply qualitatively distinct contributions
      of eyes and head in gaze allocation. This underlines the care that needs to be
      taken when inferring real-world behavior from constrained laboratory data.

PMID- 23001371
TI  - Optimizing the control of high ID movements: rethinking the obvious.
AB  - An experiment was designed to determine the degree to which instruction and
      visual display influence participants' performance and control characteristics
      when executing difficult reciprocal aiming movements. Participants were randomly
      assigned to one of the three acquisition conditions (Fitts, Impulse and Sine).
      Participants in the Fitts condition were asked to flex/extend their limb/lever in
      the horizontal plane at the elbow joint (wrist stabilized) in an attempt to move
      back and forth between two targets as quickly and accurately as possible. In the
      Impulse condition, participants moved between two target lines paced by a
      metronome, and in the Sine condition, participants were asked to track a sine
      wave pattern. The timing for the Impulse and Sine conditions was set to result in
      total times (movement time + dwell time) similar to that observed in our previous
      experiments using the same Fitts conditions. The respective display and current
      position of the limb were projected on the screen in front of the participant.
      Following nine acquisition trials (15 s each) under their assigned condition,
      Test 1 was conducted under the same conditions as the participant experienced
      during the acquisition, and then, Test 2 was conducted for all participants under
      the Fitts' conditions. The results for Test 1 indicated that total time and
      movement time for the three groups did not differ. However, dwell time was
      significantly lower, a larger proportion of movement time was spent in the
      acceleration portion of the movement, and peak velocity was significantly lower
      for the participants in the Sine condition than for participants in the Fitts
      condition. On Test 2, where Fitts conditions were imposed, the Sine group
      outperformed the Fitts condition on all variables except hits and endpoint
      variability where the Fitts and Sine groups performed similarly.

PMID- 23001372
TI  - Enhancing memory of stair height by the motor experience of stepping.
AB  - A concept emerging from recent studies on obstacle avoidance in quadrupeds is
      that working memory of the height of an obstacle established by visual
      information is enhanced by motor interactions with the obstacle. In this
      investigation, we found that this concept is valid in adult humans when viewing
      and walking up stairs. The main finding was that the memory of the height of
      stairs was enhanced when information about stair height was gained by walking up
      a short flight of stairs compared to when information about stair height was
      gained by vision alone. By measuring the maximum toe clearance when subjects step
      onto a stair, we observed that maximum toe clearance increased after diverting
      vision from the stair for a few seconds prior to stepping. Most of this increase
      occurred within a 2-s period between diverting vision from the stair and
      initiating the step. By contrast, this increase in maximum toe clearance after
      diverting vision from a stair was significantly reduced after subjects walked up
      two stairs prior to stepping onto a stair without vision. This reduction
      persisted for delays as long as 10 s between diverting vision from the stair and
      initiating the step. In four of twelve subjects, the maximum toe clearance after
      these long periods without vision of the stair was close to the value when steps
      were made with full vision of the stairs.

PMID- 23001373
TI  - Risk of hypervascularization in small hypovascular hepatic nodules showing
      hypointense in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients
      with chronic liver disease.
AB  - PURPOSE: The purpose of this study was to elucidate the incidence and risk
      factors for the progression of hypointense nodules observed in the hepatobiliary
      phase of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced
      MRI) of hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      Hypovascular nodules (112) showing hypointensity in the hepatobiliary phase of Gd
      EOB-DTPA-enhanced MRI were examined in 54 patients. All patients underwent
      computed tomography during hepatic arteriography and computed tomography during
      arterial portography (CTAP) within a month after Gd-EOB-DTPA-enhanced MRI.
      According to the tumor size, 112 nodules were divided into two groups: those >10
      mm in diameter (group A, n = 39) and those <=10 mm in diameter (group B, n = 73).
      The incidence of progression to hypervascular HCC was calculated using the Kaplan
      Meier method. RESULTS: The incidence of hypervascularization was significantly
      higher in group A nodules than in group B nodules (p < 0.0001). Tumor size (p <
      0.0001) and hypoattenuation in CTAP (p = 0.0004) showed significant correlation
      with hypervascularization. CONCLUSION: Hypointense nodules observed in the
      hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI with diameters of >10 mm had a
      high probability of hypervascularization.

PMID- 23001374
TI  - Negatively charged superparamagnetic iron oxide nanoparticles: a new blood
      pooling magnetic resonance contrast agent.
AB  - PURPOSE: Our purpose was to investigate the utility of superparamagnetic iron
      oxide nanoparticles (SPIO) as a blood-pooling contrast agent at magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: We studied four contrast agents:
      carboxymethyl-diethylaminoethyl dextran magnetite SPIO (CMEADM-S, diameter 54
      nm), negatively charged CMEADM ultrasmall SPIO (CMEADM-U, 32 nm), alkali-treated
      dextran magnetite SPIO (ATDM-S, 55 nm), and ATDM ultrasmall SPIO (ATDM-U, 28 nm)
      carrying a neutral charge. Each contrast agent (80 MUmol/kg) was injected
      intraperitoneally into apolipoprotein E (apoE) mice and the tissue iron
      concentration was measured 30-, 60-, 180-, and 300-min later by nuclear MR. For
      MR angiographic (MRA) evaluation, we injected the agents into the auricular vein
      of four groups of 15 rabbits. Immediately and 30-, 60-, 180-, and 300-min later,
      three rabbits from each group were subjected to MRI. The organ/background signal
      ratio (SR) was calculated. Statistical analyses were performed with Tukey's
      honestly significant difference (HSD) test. RESULTS: At 60 and 180 min, blood
      iron concentration of CMEADM-U was significantly different from other contrast
      agents. In the abdominal aorta and inferior vena cava, SR of CMEADM-U was higher
      at 180 and 300 min than of the other contrast agents. In the thoracic aorta,
      there was no difference in SR at 300 min between CMEADM-U and CMEADM-S.
      CONCLUSION: Negatively charged SPIO nanoparticles may be useful as a blood
      pooling contrast agent.

PMID- 23001375
TI  - Enhanced phosphoinositide 3-kinase(p110alpha) activity prevents diabetes-induced
      cardiomyopathy and superoxide generation in a mouse model of diabetes.
AB  - AIMS/HYPOTHESIS: Diabetic cardiomyopathy is characterised by diastolic
      dysfunction, oxidative stress, fibrosis, apoptosis and pathological cardiomyocyte
      hypertrophy. Phosphoinositide 3-kinase (PI3K)(p110alpha) is a cardioprotective
      kinase, but its role in the diabetic heart is unknown. The aim of this study was
      to assess whether PI3K(p110alpha) plays a critical role in the induction of
      diabetic cardiomyopathy, and whether increasing PI3K(p110alpha) activity in the
      heart can prevent the development of cardiac dysfunction in a setting of
      diabetes. METHODS: Type 1 diabetes was induced with streptozotocin in adult male
      cardiac-specific transgenic mice with increased PI3K(p110alpha) activity
      (constitutively active PI3K [p110alpha], caPI3K] or decreased PI3K(p110alpha)
      activity (dominant-negative PI3K [p110alpha], dnPI3K) and non-transgenic (Ntg)
      mice for 12 weeks. Cardiac function, histological and molecular analyses were
      performed. RESULTS: Diabetic Ntg mice displayed diastolic dysfunction and
      increased cardiomyocyte size, expression of atrial and B-type natriuretic
      peptides (Anp, Bnp), fibrosis and apoptosis, as well as increased superoxide
      generation and increased protein kinase C beta2 (PKCbeta2), p22 ( phox ) and
      apoptosis signal-regulating kinase 1 (Ask1) expression. Diabetic dnPI3K mice
      displayed an exaggerated cardiomyopathy phenotype compared with diabetic Ntg
      mice. In contrast, diabetic caPI3K mice were protected against diastolic
      dysfunction, pathological cardiomyocyte hypertrophy, fibrosis and apoptosis.
      Protection in diabetic caPI3K mice was associated with attenuation of left
      ventricular superoxide generation, attenuated Anp, Bnp, PKCbeta2, Ask1 and p22 (
      phox ) expression, and elevated AKT. Further, in cardiomyocyte-like cells,
      increased PI3K(p110alpha) activity suppressed high glucose-induced superoxide
      generation and enhanced mitochondrial function. CONCLUSIONS/INTERPRETATION: These
      results demonstrate that reduced PI3K activity accelerates the development of
      diabetic cardiomyopathy, and that enhanced PI3K(p110alpha) activity can prevent
      adverse cardiac remodelling and dysfunction in a setting of diabetes.

PMID- 23001376
TI  - Implementation of the automated Leicester Practice Risk Score in two diabetes
      prevention trials provides a high yield of people with abnormal glucose
      tolerance.
AB  - AIMS/HYPOTHESIS: The Leicester Practice Risk Score (LPRS) is a tool for
      identifying those at high risk of either impaired glucose regulation (IGR),
      defined as impaired glucose tolerance and/or impaired fasting glucose, or type 2
      diabetes from routine primary care data. The aim of this study was to determine
      the yield from the LPRS when applied in two diabetes prevention trials. METHODS:
      Let's Prevent Diabetes (LPD) and Walking Away from Diabetes (WAD) studies used
      the LPRS to identify people at risk of IGR or type 2 diabetes from 54 general
      practices. The top 10% at risk within each practice were invited for screening
      using a 75 g OGTT. The response rate to the invitation and the prevalence of IGR
      and/or type 2 diabetes in each study were calculated. RESULTS: Of those invited
      19.2% (n = 3,449) in LPD and 22.1% (n = 833) in WAD attended. Of those screened
      for LPD 25.5% (95% CI 24.1, 27.0) had IGR and 4.5% (95% CI 3.8, 5.2) had type 2
      diabetes, giving a prevalence of any abnormal glucose tolerance of 30.1% (95% CI
      28.5, 31.6). Comparable rates were seen for the WAD study: IGR 26.5% (95% CI
      23.5, 29.5), type 2 diabetes 3.0% (95% CI 1.8, 4.2) and IGR/type 2 diabetes 29.5%
      (95% CI 26.4, 32.6). CONCLUSIONS/INTERPRETATION: Using the LPRS identifies a high
      yield of people with abnormal glucose tolerance, significantly higher than those
      seen in a population screening programme in the same locality. The LPRS is an
      inexpensive and simple way of targeting screening programmes at those with the
      highest risk.

PMID- 23001377
TI  - A two-step screening algorithm including fasting plasma glucose measurement and a
      risk estimation model is an accurate strategy for detecting gestational diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: It is currently not clear how to construct a time- and cost
      effective screening strategy for gestational diabetes mellitus (GDM). Thus, we
      elaborated a simple screening algorithm combining (1) fasting plasma glucose
      (FPG) measurement; and (2) a multivariable risk estimation model focused on
      individuals with normal FPG levels to decide if a further OGTT is indicated.
      METHODS: A total of 1,336 women were prospectively screened for several risk
      factors for GDM within a multicentre study conducted in Austria. Of 714 women
      (53.4%) who developed GDM using recent diagnostic guidelines, 461 were
      sufficiently screened with FPG. A risk prediction score was finally developed
      using data from the remaining 253 women with GDM and 622 healthy women. The
      screening algorithm was validated with a further 258 pregnant women. RESULTS: A
      risk estimation model including history of GDM, glycosuria, family history of
      diabetes, age, preconception dyslipidaemia and ethnic origin, in addition to FPG,
      was accurate for detecting GDM in participants with normal FPG. Including an FPG
      pretest, the receiver operating characteristic AUC of the screening algorithm was
      0.90 (95% CI 0.88, 0.91). A cut-off value of 0.20 was able to differentiate
      between low and intermediate risk for GDM with a high sensitivity. Comparable
      results were seen with the validation cohort. Moreover, we demonstrated an
      independent association between values derived from the risk estimation and
      macrosomia in offspring (OR 3.03, 95% CI 1.79, 5.19, p < 0.001).
      CONCLUSIONS/INTERPRETATION: This study demonstrates a new concept for accurate
      but cheap GDM screening. This approach should be further evaluated in different
      populations to ensure an optimised diagnostic algorithm.

PMID- 23001378
TI  - Islet nerves in focus--defining their neurobiological and clinical role.
AB  - Although it is well established that the pancreatic islets are innervated by
      autonomic nerves, the detailed islet innervation pattern is still unclear. In
      this issue of Diabetologia (DOI: 10.1007/s00125-012-2699-6 ) novel details of the
      islet neuroanatomy and its plasticity in experimental diabetes are described. By
      using a 3-dimensional (3-D) imaging technique, it has been shown that, in islets
      from normal mice, sympathetic nerves mainly form a neurovascular complex in
      addition to innervating peripherally located islet alpha cells. There are also
      pronounced changes in islet neuroanatomy in experimental diabetes. These findings
      suggest novel neural-islet regulatory mechanisms as well as neural involvement in
      the development of diabetes, and therefore advance both basic and clinical
      knowledge of islet neurobiology.

PMID- 23001379
TI  - Expert's comment concerning grand rounds case entitled ''postoperative
      pharyngocutaneous fistula: treated with sternocleidomastoid flap repair and
      cricopharyngeus myotomy'' (by V.A. Iyoob).
AB  - Great care should be taken to minimise damage to the pharynx and upper oesophagus
      during an anterior approach to the cervical spine. If noticed at the time of
      surgery primary repair should be carried out; if noticed in the postoperative
      period, thorough cleaning and placement of a pharyngocutaneous drain will result
      in spontaneous healing of the majority of fistula. For persistent fistula
      secondary repair is required using well-vascularised tissue.

PMID- 23001380
TI  - An uncommon case of Mycoplasma hominis infection after total disc replacement.
AB  - PURPOSE: Beside mechanical complications, the majority of adverse events after
      total disc arthroplasty (TDA) are related to the surgical approach. Septic
      complications are very uncommon and only one previous case has been published.
      The objective of this article is to describe the clinical circumstances,
      treatment, and outcomes of septic complication after TDA at L4-L5, involving an
      uncommon pathogen (Mycoplasma hominis). METHODS: A 38-year-old woman underwent a
      MobiDisc((r)) TDA at L4-L5 level for discogenic pain. One month postoperatively,
      she complained of acute low back and abdominal pain associated with fever (39 
      degrees C). C-reactive protein level was elevated (197 mg/L; normal <5 mg/L) and
      the white blood cell count was normal (7 * 10(9)/L; normal 4-10 * 10(9)/L). A
      computerized tomography (CT) showed a left psoas-based retroperitoneal abscess.
      Treatment consisted of open debridement, drainage and empirical antibiotic
      therapy. Intraoperative cultures yielded M. hominis after 7 days incubation.
      Antibiotic therapy was adapted and discontinued after 2 months. The patient had
      failed to mention earlier that she had been suffering from abnormal vaginal
      discharge for some time and was using an intrauterine contraceptive device.
      RESULTS: At 1.5-year follow-up, review confirmed healing of the infection with
      biological normalization without residual collection, radiolucent lines or
      osteolysis around the prosthesis at radiographs, CT and MRI. CONCLUSIONS:
      Mycoplasma hominis can be involved as an extragenital pathogen in musculoskeletal
      infections. Because its culture and identification are difficult, special media
      and real-time PCR are required in case of postoperative deep wound infection
      after anterior lumbar spine surgery, especially in the case of previous
      genitourinary infections, to decrease the delay in diagnosis and treatment.

PMID- 23001381
TI  - A methodological, systematic review of evidence-based independent risk factors
      for surgical site infections after spinal surgery.
AB  - OBJECTIVE: To identify the independent risk factors, based on available evidence
      in the literature, for patients developing surgical site infections (SSI) after
      spinal surgery. METHODS: Non-interventional studies evaluating the independent
      risk factors for patients developing SSI following spinal surgery were searched
      in Medline, Embase, Sciencedirect and OVID. The quality of the included studies
      was assessed by a modified quality assessment tool that had been previously
      designed for observational studies. The effects of studies were combined with the
      study quality score using a best-evidence synthesis model. RESULTS: Thirty-six
      observational studies involving 2,439 patients with SSI after spinal surgery were
      identified. The included studies covered a wide range of indications and surgical
      procedures. These articles were published between 1998 and 2012. According to the
      quality assessment criteria for included studies, 15 studies were deemed to be
      high-quality studies, 5 were moderate-quality studies, and 16 were low-quality
      studies. A total of 46 independent factors were evaluated for risk of SSI. There
      was strong evidence for six factors, including obesity/BMI, longer operation
      times, diabetes, smoking, history of previous SSI and type of surgical procedure.
      We also identified 8 moderate-evidence, 31 limited-evidence and 1 conflicting
      evidence factors. CONCLUSION: Although there is no conclusive evidence for why
      postoperative SSI occurs, these data provide evidence to guide clinicians in
      admitting patients who will have spinal operations and to choose an optimal
      prophylactic strategy. Further research is still required to evaluate the effects
      of these above risk factors.

PMID- 23001383
TI  - Approximate-model closed-loop minimal sampling method for HIV viral-load minima
      detection.
AB  - We present a closed-loop method for determining the minimum of a viral rebound
      curve for an HIV patient undergoing a therapy transition. This method fits the
      parameters for a reduced approximate solution to the viral load measurements
      using a Simulated Annealing direct search algorithm. Gaussian white noise is
      added, and a family of fits is obtained. A safety tolerance measure is applied to
      the family of fits to obtain the next sample time. Using parameters identified
      from HIV data, we show that this method exhibits robust performance on noisy data
      generated from identified patient models, while greatly reducing the number of
      samples needed compared to a fixed-interval sampling approach.

PMID- 23001384
TI  - Direct immobilization of oxyamine-modified proteins from cell lysates.
AB  - Oxyamine-modified proteins can be efficiently and selectively immobilized on
      ketone-coated glass slides at neutral pH in short reaction times by direct
      treatment and spotting of protein expression lysates without prior purification.

PMID- 23001382
TI  - Integrating bipolar disorder management in primary care.
AB  - There is growing realization that persons with bipolar disorder may exclusively
      be seen in primary (general medical) care settings, notably because of limited
      access to mental health care and stigma in seeking mental health treatment. At
      least two clinical practice guidelines for bipolar disorder recommend
      collaborative chronic care models (CCMs) to help integrate mental health care to
      better manage this illness. CCMs, which include provider guideline support, self
      management support, care management, and measurement-based care, are well
      established in primary care settings, and may help primary care practitioners
      manage bipolar disorder. However, further research is required to adapt CCMs to
      support complexities in diagnosing persons with bipolar disorder, and integrate
      decision-making processes regarding medication safety and tolerability in primary
      care. Additional implementation studies are also needed to adapt CCMs for persons
      with bipolar disorder in primary care, especially those seen in smaller practices
      with limited infrastructure and access to mental health care.

PMID- 23001385
TI  - An engineered lantipeptide synthetase serves as a general leader peptide
      dependent kinase.
AB  - Phosphorylation is an abundant post-translational modification involved in a
      myriad of cell signaling pathways. Herein, we have engineered the class II
      lantipeptide synthetase ProcM to generate a variety of peptides containing O
      phosphoserine (pSer) and O-phosphothreonine (pThr) residues, either in vitro or
      in vivo.

PMID- 23001386
TI  - Influence of sample processing on the analysis of carotenoids in maize.
AB  - We performed a number of tests with the aim to develop an effective extraction
      method for the analysis of carotenoid content in maize seed. Mixtures of methanol
      ethyl acetate (6:4, v/v) and methanol-tetrahydrofuran (1:1, v/v) were the most
      effective solvent systems for carotenoid extraction from maize endosperm under
      the conditions assayed. In addition, we also addressed sample preparation prior
      to the analysis of carotenoids by liquid chromatography (LC). The LC response of
      extracted carotenoids and standards in several solvents was evaluated and results
      were related to the degree of solubility of these pigments. Three key factors
      were found to be important when selecting a suitable injection solvent:
      compatibility between the mobile phase and injection solvent, carotenoid polarity
      and content in the matrix.

PMID- 23001387
TI  - Association of KIF6 variant with lipid level and angiographic coronary artery
      disease events risk in the Han Chinese population.
AB  - KIF6 is a class of molecular motor from the kinesin superfamily. Recently,
      multiple large studies consisting mainly of Europeans have shown that KIF6
      Trp719Arg SNP may be a new predictive factor for coronary artery disease (CAD)
      event risk. The allelic frequency distribution of rs20455 is different in various
      populations, yet studies among the Han population, one of the largest ethnic
      groups in the World, have not been conducted. This study is aimed to evaluate the
      association of KIF6 Trp719Arg variant with angiographic CAD and serum lipid
      levels in the Han population from northern China. In this case-controlled study,
      peripheral blood samples were collected from 356 patients and 568 controls of Han
      Chinese origin. Genotyping was performed by a high-resolution melting curve. The
      impact of rs20455 on CAD and non-fatal MI was evaluated in a dominant genetic
      model with stepwise multiple regression analysis. There were no significant
      differences of genotypes and allele frequency between angiographic CAD and
      control groups (p > 0.05); however, that of MI and non-MI subgroups were
      significant differences (p < 0.05). After adjusting for significant risk factors,
      angiographic CAD risk was not significantly increased in 719Arg allele carriers
      compared with non-carriers. Further analysis revealed that the non-fatal MI risk
      and triglyceride levels were significantly higher in 719Arg allele carriers than
      non-carriers. In conclusion, KIF6 719Arg allele was not an independent risk
      factor for angiographic CAD susceptibility in Han populations from northern
      China. However, it was associated with a significantly higher TG level, which may
      indicate an increased myocardial infarction risk in angiographic CAD patients.

PMID- 23001388
TI  - In vitro antioxidant properties of flavonoids and polysaccharides extract from
      tobacco (Nicotiana tabacum L.) leaves.
AB  - In the present study, antioxidant properties of flavonoids and polysaccharides
      from tobacco (Nicotiana tabacum L.) leaves were evaluated in several in vitro
      systems, e.g., scavenging activities on hydroxyl, superoxide anion, 1,1-diphenyl
      2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic
      acid) (ABTS) radicals, and reducing power. Flavonoids showed much better activity
      than polysaccharides in scavenging activities on free radicals. When compared to
      the positive control, ascorbic acid, both showed weaker antioxidant potential.
      However, flavonoids possessed comparable superoxide anion, DPPH and ABTS radical
      scavenging abilities to ascorbic acid at high concentration (600 MUg/mL).
      Meanwhile, it was found that flavonoids had prominent effects on the reducing
      power, which was equivalent to ascorbic acid, and was significantly higher than
      polysaccharides. These results clearly indicate that flavonoids are effective in
      scavenging free radicals and have the potential to be powerful antioxidants.
      Thus, tobacco leaves could be considered as a potential source of natural
      antioxidants for food, pharmaceutical, cosmetics or nutraceutical industries.

PMID- 23001390
TI  - Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and
      sustained activation of p38 MAPK.
AB  - Galangin, an active flavonoid present at high concentration in Alpinia
      officinarum Hance and propolis, shows cytotoxicity towards several cancer cell
      lines, including melanoma. However, the specific cellular targets of galangin
      induced cytotoxicity in melanoma are still unknown. Here, we investigated the
      effects of galangin in B16F10 melanoma cells and explored the possible molecular
      mechanisms. Galangin significantly decreased cell viability of B16F10 cells, and
      also induced cell apoptosis shown by Hoechst 33342 staining and Annexin V-PI
      double staining flow cytometric assay. Furthermore, upon galangin treatment,
      disruption of mitochondrial membrane potential was observed by JC-1 staining.
      Western blotting analysis indicated that galangin activated apoptosis signaling
      cascades by cleavage of procaspase-9, procaspase-3 and PARP in B16F10 cells.
      Moreover, galangin significantly induced activation of phosphor-p38 MAPK in a
      time and dose dependent manner. SB203580, an inhibitor of p38, partially
      attenuated galangin-induced apoptosis in B16F10 cells. Taken together, this work
      suggests that galangin has the potential to be a promising agent for melanoma
      treatment and may be further evaluated as a chemotherapeutic agent.

PMID- 23001391
TI  - Set-shifting among adolescents with bulimic spectrum eating disorders.
AB  - OBJECTIVE: Set-shifting difficulties are observed among adults with bulimia
      nervosa (BN). This study aimed to assess whether adolescents with BN and BN
      spectrum eating disorders exhibit set-shifting problems relative to healthy
      controls. METHODS: Neurocognitive data from 23 adolescents with BN were compared
      with those from 31 adolescents with BN-type eating disorder not otherwise
      specified and 22 healthy controls on various measures of set-shifting (Trail
      Making Task [shift task], Color-Word Interference, Wisconsin Card Sorting Test,
      and Brixton Spatial Anticipation Task). RESULTS: No significant differences in
      set-shifting tasks were found among groups (p >.35), and effect sizes were small
      (Cohen f < 0.17). CONCLUSIONS: Cognitive inflexibility may develop over time
      because of the eating disorder, although it is possible that there is a subset of
      individuals in whom early neurocognitive difficulty may result in a longer
      illness trajectory. Future research should investigate the existence of
      neurocognitive taxons in larger samples and use longitudinal designs to fully
      explore biomarkers and illness effects. TRIAL REGISTRATION: clinicaltrials.gov
      NCT00879151.

PMID- 23001392
TI  - Hypothalamic-pituitary-thyroid axis function in women with a menstrually related
      mood disorder: association with histories of sexual abuse.
AB  - INTRODUCTION: We previously reported a unique hypothalamic-pituitary-thyroid
      (HPT) axis profile in women with a menstrually related mood disorder (MRMD) who
      also had a history of sexual abuse (SA). In the present study, we sought to
      extend that work by examining the association of an SA history with HPT-axis
      disturbance in both women with MRMD and women without MRMD. METHODS: Fifty-seven
      women met the prospective criteria for MRMD (23 with an SA history), and 52 women
      were non-MRMD (18 with an SA history). Thyroid-stimulating hormone, thyroxin (T4;
      total and free), and triiodothyronine (T3; total and free) were evaluated in
      serum, together with thyroid hormone ratios reflecting T4 to T3 conversion.
      RESULTS: Women with MRMD, compared with women without MRMD, had elevated T3/T4
      ratios (p values <= .01; reflecting increased conversion of T4 to T3) and lower
      free and total T4 concentrations (p values = .01). Higher T3/T4 ratios and lower
      T4 concentrations predicted more severe premenstrual symptoms in all women. An SA
      history, irrespective of MRMD status, was associated with elevated thyroid
      stimulating hormone concentrations (p = .03). However, in women with MRMD, an SA
      history was associated with elevated T3 concentrations (p = .049), whereas in
      women without MRMD, an SA history was associated with decreased T3 concentrations
      (p = .02). CONCLUSIONS: An MRMD and an SA history are associated with independent
      and interactive effects on the HPT axis. The evidence that an MRMD moderates the
      influence of SA on T3 concentrations contributes to a growing body of work
      suggesting that an SA history may identify a distinct subgroup of women with
      MRMD.

PMID- 23001394
TI  - Effects of a periodized small-sided game training intervention on physical
      performance in elite professional soccer.
AB  - The present study examined the effects of periodized small-sided game (SSG)
      training intervention during a 4-week in-season break on the physical performance
      changes (i.e., speed, aerobic performance, and repeated sprint ability) within
      elite European soccer players. Fifteen, elite, male, professional players (age:
      24.5 +/- 3.45 years; height: 181.1 +/- 5.78 cm; body mass: 78.7 +/- 7.67 kg;
      VO2max: 54.88 +/- 5.25 ml.kg(-1).min(-1)) from a Scottish Premier League team
      participated in 7 separate SSG sessions (3 vs. 3 plus goalkeepers) of which games
      lasted for a 3-minute duration for the selected number of games (ranged from 5 to
      11) increasing over the intervention period. To examine the effects of the SSG
      intervention on physical performance changes, pre- and posttesting sessions took
      place over a 2-day period (day 1: anthropometry and repeated sprint ability [RSA]
      assessments; day 2: running economy [RE] and blood lactate assessments). Results
      show that the 4-week SSG training intervention induced significant improvement in
      RSA as indicated by faster 10-m sprint time (p < 0.05, small effect), total
      sprint time (p < 0.05, medium effect), and smaller percentage decrement score (p
      < 0.05, medium effect). Furthermore, the SSGs also led to an improvement in RE as
      indicated through significantly reduced VO2 and heart rate at running speed 9,
      11, and 14 km.h(-1) (all p's < 0.05, large effects). In conclusion, the present
      study demonstrates that implementing a periodized SSG training intervention
      during the 4-week in-season break is capable of improving elite-level soccer
      players' physical fitness characteristics. Being able to develop physical
      characteristics in conjunction to technical and tactical elements of the game,
      within a relatively short period, makes SSGs an appealing proposition for fitness
      coaches, players, and technical coaches alike.

PMID- 23001395
TI  - The effects of serial and acute NaHCO3 loading in well-trained cyclists.
AB  - Many studies have reported substantial performance gains in well-trained athletes
      after the acute ingestion of sodium bicarbonate (NaHCO3). However, acute NaHCO3
      ingestion is not always practical. The aim of this study was to compare acute
      NaHCO3 loading with serial NaHCO3 loading (split doses over 3 days) in well
      trained cyclists. Eight male cyclists (mean +/- SD; age = 28 +/- 8 years; VO2peak
      = 66.8 +/- 8.4 ml.kg(-1).min(-1)) completed 3 tests in a double-blind, randomized
      design over a 3-week timeframe: acute NaHCO3 loading (AL), serial NaHCO3 loading
      (SL), and a placebo loading condition (P). After each loading protocol, the
      cyclists completed a 4-minute performance test on a cycling ergometer. The VO2
      was measured during each test, and blood samples were taken throughout the study
      to measure lactate, bicarbonate ion concentration ([HCO3(-)]), and pH levels.
      Both the AL and SL trials produced a significantly higher average power in the 4
      minute test (mean +/- SD; 3.3 +/- 2.0 and 2.3 +/- 2.5%; p < 0.001 and p = 0.01,
      respectively) when compared with the P trial, with no significant difference
      between AL and SL trials (p = 0.29). The AL trial produced a significantly
      greater postloading alkalosis as determined by blood [HCO3(-)] when compared with
      the SL and P trials. Both acute and serial NaHCO3 loading significantly improved
      4-minute cycling performance when compared with that in a placebo trial. However,
      serial NaHCO3 loading may provide a convenient and practical alternative approach
      for athletes preparing for competition.

PMID- 23001396
TI  - A lithium-organic framework with coordinatively unsaturated metal sites that
      reversibly binds water.
AB  - The synthesis and characterisation of a three-dimensional lithium-organic
      framework MIL-145 is described, which upon thermal treatment yields a second open
      framework, MIL-146, that contains four and three-coordinate lithium centres: the
      coordinatively unsaturated trigonal planar lithium centres are able to reversibly
      bind water with crystallinity maintained, while the dehydrated phase shows
      preferential adsorption of CO(2) over N(2).

PMID- 23001393
TI  - The impact of premorbid and postmorbid depression onset on mortality and cardiac
      morbidity among patients with coronary heart disease: meta-analysis.
AB  - BACKGROUND: Depression is associated with increased cardiac morbidity and
      mortality in the general population and in patients with coronary heart disease
      (CHD). Recent evidence suggests that patients with new-onset depression post-CHD
      diagnosis have worse outcomes than do those who had previous or recurrent
      depression. This meta-analysis investigated the timing of depression onset in
      established CHD and CHD-free cohorts to determine what time frame is associated
      with greater mortality and cardiac morbidity. METHODOLOGY/PRINCIPAL FINDINGS: The
      MEDLINE, EMBASE, and PsycINFO databases were searched systematically to identify
      articles examining a depression time frame that specified an end point of all
      cause mortality, cardiac mortality, rehospitalization, or major adverse cardiac
      events. A meta-analysis was conducted to estimate effect sizes by time frame of
      depression. Twenty-two prospective cohort studies were identified. Nine studies
      investigated premorbid depression in CHD-free cohorts in relation to cardiac
      death. Thirteen studies in patient samples with CHD examined new-onset depression
      in comparison with previous or recurrent depression. The pooled effect size (risk
      ratio) was 0.76 (95% confidence interval (CI) = 0.48-1.19) for history of
      depression only, 1.79 (95% CI = 1.45-2.21) for premorbid depression onset, 2.11
      (95% CI = 1.66-2.68) for postmorbid or new depression onset, and 1.59 (95% CI =
      1.08-2.34) for recurrent depression. CONCLUSIONS/SIGNIFICANCE: Both premorbid and
      postmorbid depression onsets are potentially hazardous, and the question of
      timing may be irrelevant with respect to adverse cardiac outcomes. However, the
      combination of premorbid depression with the absence of depression at the time of
      a cardiac event (i.e., historical depression only) is not associated with such
      outcomes and deserves further investigation.

PMID- 23001397
TI  - Potential sources affecting the activity concentrations of 238U, 235U, 232Th and
      some decay products in lettuce and wheat samples.
AB  - The activity concentrations of radionuclides within the uranium and thorium
      series were determined in wheat and lettuce at five sites in France, and in their
      respective potential sources: crop soils of wheat and crop soils and irrigation
      waters of lettuce. These data were used to calculate concentration ratios and to
      enrich the database supported by the technical report series N degrees 472 of the
      IAEA (2010). For wheat and lettuce, the activity concentrations were in the same
      range for all radionuclides studied, except for (210)Pb, which had higher
      activity concentrations in wheat, ranging between 1.3 and 11 Bq kg(-1) (fresh
      weight) as compared to 0.4 and 0.7 Bq kg(-1) (fresh weight) for lettuce. For
      wheat, the range of activity concentrations (mBq kg(-1); fresh weight) decreased
      as (210)Pb > (226)Ra (56-1511) ~ (228)Ra (86-769) > (228)Th (19-176) ~ (238)U (11
      169) ~ (234)U (12-150) ~ (230)Th (9.08-197.18) ~ (232)Th (8.61-121.45) > (235)U
      (0.53-7.9). For lettuce, it decreased as (228)Ra (<320-1221) > (210)Pb (409-746)
      > (226)Ra (30-599) ~ (228)Th (<29-347) > (238)U (8-120) ~ (234)U (8-121) ~
      (230)Th (5.21-134.63) ~ (232)Th (5.25-156.99) > (235)U (0.35-5.63). The species
      differences may reflect different plant physiologies. Through the study of
      activity ratios of wheat and lettuce in relation with those of the various
      radionuclide sources it has been possible to highlight the contribution of the
      main sources of natural radionuclides. Indeed, irrigation water when the uranium
      concentration is enhanced (>30 mBq L(-1)) contributed significantly to the
      activity concentration of uranium in lettuces. Concerning the high activity
      concentrations of (210)Pb, it could be explained by atmospheric particle
      deposition. The effect of soil particles resuspension and their adhesion to the
      plant surface seemed to be important in some cases. The soil-to-plant transfer
      factors were calculated for lettuce and wheat. The values were lower in wheat
      than in lettuce except for (210)Pb which had similar values in the two species
      (0.11-0.13 respectively). For both species, (210)Pb followed by (228)Ra (0.015
      0.10) and (226)Ra (0.010-0.051) displayed the highest transfer factor, whereas
      (238)U had intermediate values (0.0015-0.030) and (232)Th exhibited the lowest
      (0.0014-0.013).

PMID- 23001398
TI  - Catuaba (Trichilia catigua) prevents against oxidative damage induced by in vitro
      ischemia-reperfusion in rat hippocampal slices.
AB  - Oxidative stress is implicated in brain damage associated with ischemia
      reperfusion. Natural antioxidants found in some plants used in folk medicine have
      been indicated as potential neuroprotective agents. Here we investigated whether
      Trichilia catigua, a traditional Brazilian herbal medicine alleged to exhibit a
      variety of neuropharmacological properties (antidepressant, anti-neurasthenic,
      anti-inflammatory etc.), could have neuroprotective properties in rat hippocampal
      slices subjected to 2 h oxygen and glucose deprivation (OGD) followed by 1 h
      reperfusion. Ischemia-reperfusion (I/R) significantly decreased mitochondrial
      viability, increased dichlorofluorescein oxidation above control both in the
      incubation medium and slices homogenates, increased lactate dehydrogenase into
      the incubation medium and decreased non-protein thiols. T. catigua (40-100
      MUg/mL) protected slices from the deleterious effects of OGD when present before
      OGD and during the reperfusion periods. Oxidative stress in the medium was also
      determined under different conditions and the results demonstrated that T.
      catigua could not protect slices from I/R when it was added to the medium after
      ischemic insult. Although the translation to a real in vivo situation of I/R is
      difficult to be done, the results indicated that T. catigua should be used as
      preventive and not as a curative agent against brain damage.

PMID- 23001399
TI  - Bog bilberry anthocyanin extract improves motor functional recovery by
      multifaceted effects in spinal cord injury.
AB  - The aim of this study was to determine the therapeutic efficiency of bog bilberry
      anthocyanin extract (BBAE) treatment starting 1 d after spinal cord injury (SCI)
      in rats and to investigate the underlying mechanism. The BBAE contained cyanidin
      3-glucoside, malvidin-3-galactoside and malvidin-3-glucoside. SCI models were
      induced using the weight-drop method in Sprague-Dawley rats and additionally with
      sham group (laminectomy only). The animals were divided into four groups: vehicle
      treated group; 10 mg/kg BBAE-treated group; 20 mg/kg BBAE-treated group; sham
      group. BBAE-treated or vehicle-treated group was administered orally at one day
      after SCI and then daily for 8 weeks. Locomotor functional recovery was assessed
      during the 8 weeks post operation period by performing a Basso, Beattie, and
      Bresnahan (BBB) locomotor score test. At the end of study, the animals were
      killed, and 1.5 cm segments of spinal cord encompassing the injury site were
      removed for immunohistochemistry, histopathological and western blotting
      analysis. Immunohistochemistry for GFAP, aggrecan, neurocan and NeuN was used to
      assess the degree of astrocytic glial scar formation and neuron survival.
      Immunohistochemistry and western blotting analysis for TNF-alpha, IL-6, IL-1beta
      was used to evaluate the anti-inflammation effect of BBAE. To evaluate its
      inhibition effect on the astrocytes, we performed the MTT assay and
      immunohistochemistry for Ki67 in vitro. Results show that the BBAE-treated
      animals showed significantly better locomotor functional recovery, neuron death
      and smaller glial scar formation after spinal cord injury in vivo. In addition,
      BBAE administration could inhibit astrocyte proliferation in vivo and vitro.
      Therefore, BBAE may be useful as a promising therapeutic agent for SCI.

PMID- 23001400
TI  - Chemical components separation with botulinum toxin A: a novel technique to
      improve primary fascial closure rates of the open abdomen.
AB  - INTRODUCTION: Failure to definitively close the open abdomen (OA) after damage
      control laparotomy leads to considerable morbidity and mortality. We have
      developed a novel technique, the "chemical components separation," which
      incorporates injection of botulinum toxin A (BTX), a long-term flaccid paralytic,
      into the lateral abdominal wall musculature. METHODS: This is a retrospective
      review of all OA patients (age >=18) from December 2009-June 2010 who underwent
      BTX injection. Under ultrasound guidance, a total of 300 units of BTX were
      injected into the external oblique, internal oblique and transversus abdominus.
      RESULTS: A total of 18 patients were injected with a median age of 66 years (56 %
      male). Indications for OA treatment included questionable bowel viability (39 %),
      shock (33 %), loss of abdominal domain (6 %) and feculent contamination (17 %).
      Median ASA score was 3 with an APACHE 3 score of 85. Patients underwent a median
      of 4 serial abdominal explorations. The primary fascial closure rate was 83 %
      with a partial fascial closure rate of 6 % and planned ventral hernia rate of 11
      %. Of the 9 patients injected within 24 h of their initial OA procedure, 89 %
      achieved primary fascial closure. Mortality was 11 %; death was unrelated to BTX
      injection. The overall complication rate was 67 %; specific complications rates
      included fascial dehiscence (11 %), enterocutaneous fistula development (0 %),
      intra-abdominal abscess (44 %) and deep surgical site infection (33 %).
      CONCLUSION: The "chemical components separation" technique described is safe and
      avoids the extensive dissection necessary for mechanical components separation in
      critically ill patients with infected/contaminated abdominal domains. While
      further evaluation is required, the described technique provides potential to
      improve delayed primary fascial closure rates in the OA setting.

PMID- 23001402
TI  - The association between reflux esophagitis and psychosocial stress.
AB  - BACKGROUND: The prevalence of reflux esophagitis is increasing in Korea. Reflux
      esophagitis aggravates the stress and fatigue level of daily life, but less is
      known about the association with stress and fatigue, which could be bi
      directional. AIM: To evaluate the impact of reflux esophagitis on stress and
      fatigue and to compare the stress level of people with reflux esophagitis with
      that of controls with peptic ulcer disease and healthy controls. METHODS: Among a
      total of 9,033 subjects who underwent a comprehensive medical check-up including
      upper endoscopy, 6,834 subjects (75.7 %) were enrolled. Stress and fatigue scores
      were measured by a validated Korean version of the Brief Encounter Psychosocial
      Instrument and the Fatigue Severity Scale. RESULTS: Among 6,834 subjects, 13.2 %
      were in the high-stress group, and reflux esophagitis was found in 6.0 %. After
      adjustment for confounders, reflux esophagitis was significantly associated with
      high stress (odds ratio 1.94, 95 % confidence interval 1.25-3.02). Subjects with
      reflux esophagitis had significantly higher BEPSI-K scores compared with healthy
      controls (p = 0.027); and however, there was no significant difference in BEPSI-K
      scores between reflux esophagitis group and peptic ulcer disease controls.
      Fatigue severity scale was highly correlated with BEPSI-K (p < 0.001); however,
      there was no significant difference in fatigue severity scale level between the
      reflux esophagitis group and controls. The severity of reflux esophagitis was
      significantly correlated with BEPSI-K score (p = 0.008). CONCLUSIONS: Reflux
      esophagitis is significantly associated with psychosocial stress, and the
      severity of reflux esophagitis correlates with the degree of stress.

PMID- 23001401
TI  - Principles of polyoma- and papillomavirus uncoating.
AB  - Virus particles are vehicles for transmission of the viral genetic information
      between infected and uninfected cells and organisms. They have evolved to self
      assemble, to serve as a protective shell for the viral genome during transfer,
      and to disassemble when entering a target cell. Disassembly during entry is a
      complex, multi-step process typically termed uncoating. Uncoating is triggered by
      multiple host-cell interactions. During cell entry, these interactions occur
      sequentially in different cellular compartments that the viruses pass through on
      their way to the site of replication. Here, we highlight the general principles
      of uncoating for two structurally related virus families, the polyoma- and
      papillomaviruses. Recent research indicates the use of different compartments and
      cellular interactions for uncoating despite their structural similarity.

PMID- 23001403
TI  - Expression of ADAMTS1 and its correlation with angiogenesis in primary gastric
      cancer and lymph node metastasis.
AB  - BACKGROUND: A disintegrin and metallopeptidase with thrombospondin motif type 1
      (ADAMTS1) is a recently discovered metalloproteinase with antiangiogenic
      activity. The function of ADAMTS1 in gastric cancer remains unknown. Therefore,
      we were interested in examining ADAMTS1 expression in human gastric cancer, as
      well as its possible correlation with angiogenesis. METHODS: The mRNA and protein
      expression of ADAMTS1, thrombospondin type I (TSP1), and vascular endothelial
      growth factor (VEGF) was evaluated by RT-PCR and immunohistochemistry,
      respectively, in 56 paired tumor and normal tissue samples, and corresponding
      metastatic lymph nodes (n = 42). Microvessel density (MVD) was also evaluated by
      immunohistochemistry. RESULTS: ADAMTS1 mRNA and protein levels were significantly
      lower in primary tumors than in corresponding normal tissues, and were
      significantly higher in metastatic lymph nodes compared to their matched primary
      tumors. High ADAMTS1 mRNA and protein expression was found to be significantly
      associated with lymph node metastasis in primary tumors. There was a negative
      correlation between ADAMTS1 and VEGF mRNA and protein expression in primary
      gastric tumors and normal tissues. A negative correlation was also found between
      ADAMTS1 protein expression and MVD in primary gastric tumors. In contrast, no
      correlation was detected between ADAMTS1 and TSP1 mRNA and protein expression in
      primary gastric tumors, normal tissues, and metastatic lymph nodes. CONCLUSIONS:
      These findings suggest that ADAMTS1 expression is altered in primary gastric
      cancer and paired lymph node metastasis. In addition, ADAMTS1 has angioinhibitory
      effects in primary gastric cancer due to its low expression and negative
      correlation with VEGF and MVD. However, it appears to lose its anti-angiogenic
      activity in metastatic lymph nodes in gastric cancer.

PMID- 23001404
TI  - Improvement of thrombocytopenia in hepatitis C-related advanced fibrosis patients
      after sustained virological response.
AB  - BACKGROUND: The long-term trend of platelet count in chronic hepatitis C virus
      patients with sustained virological response (SVR) has rarely been investigated.
      AIMS: To elucidate changes of thrombocytopenia after SVR, trajectory patterns of
      platelet count over time and their associated factors. METHODS: From May 1999 to
      July 2005, a total of 135 patients (mean age 50.2 +/- 11.1 years) that received
      interferon-alpha based regimen plus ribavirin were enrolled. Platelet counts were
      followed every 6 months prospectively. The patterns of platelet counts over time
      were identified by trajectory analysis. RESULTS: Mean follow-up duration was 4.4
      +/- 1.7 years (median 4.5; range 1.0-8.5 years). Baseline platelet count in all
      and thrombocytopenic patients increase significantly at the end of follow-up,
      from 172 +/- 56 * 10(9)/l and 115 +/- 21 * 10(9)/l to 196 +/- 57 * 10(9)/l and
      148 +/- 37 * 10(9)/l, respectively (all p < 0.001). In patients with advanced
      fibrosis (n = 50), pretreatment platelet count also increased significantly (146
      +/- 45 * 10(9)/l vs. 173 +/- 51 * 10(9)/l, p < 0.001). Twenty-six of 37 (69.2 %)
      patients with pretreatment mild thrombocytopenia (100-150 * 10(9)/l) had
      normalization of platelet count, while seven of 13 (53.8 %) patients with
      pretreatment moderate to severe thrombocytopenia (<100 * 10(9)/l) had elevation
      of platelet count up to 100-150 * 10(9)/l. Three trajectory groups were
      identified, i.e., elevation (n = 43, 31.9 %), stationary (n = 79, 58.5 %), and
      decrease (n = 13, 9.6 %) groups. Multiple logistic regression showed pretreatment
      thrombocytopenia was the factor in elevation of platelet count (OR = 2.28, 95 %
      confidence interval = 1.01-5.11, p = 0.046). CONCLUSIONS: Platelet count
      increased significantly in patients with SVR after long-term follow-up. Patients
      with low baseline platelet count benefit more from SVR with respect to increased
      platelet count, compared to those with higher platelet count at baseline.

PMID- 23001405
TI  - Eosinophilic esophagitis: current treatment.
AB  - Eosinophilic esophagitis (EoE) is a relatively new entity with a significant
      amount of increased recognition over the last decade. The mainstay treatments of
      EoE are designed to eliminate the causative allergens or to reduce their effects
      on the esophageal mucosa. Common treatments include dietary modification, proton
      pump inhibitors, systemic and topical corticosteroids, and endoscopic treatments.
      As the pathogenesis of EoE is explored, new and novel treatments are being
      studied that target specific pathways and chemokines identified in as
      precipitating agents of EoE. This is a rapidly evolving field with significant
      ongoing research and clinical studies. Our review will therefore focus on current
      and novel treatment approaches to the disease.

PMID- 23001406
TI  - Prospective markers for early diagnosis and prognosis of sporadic pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND AND AIM: Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly
      lethal cancer. No proven screening strategies are available and frequent cross
      sectional imaging studies (CT/MRI) are impractical even in patients thought to be
      at higher risk than the general population. Few PDA biomarkers have been studied
      prospectively for screening. Here, we prospectively evaluated the Adnab-9
      monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for
      screening and prognostic value in sporadic PDA. We also evaluated the prognostic
      value of characterized early biomarkers in pancreaticobiliary secretions.
      METHODS: Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients
      from China and the US, respectively. Immunohistochemistry was performed in 22
      tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth
      cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9
      controls. The enriched PCR method was performed to detect K-ras mutations. ELISA
      was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg
      I). RESULTS: Adnab-9 alone was diagnostic and prognostic when measured in
      pancreatic secretions, feces, and tissues of PDA patients compared to controls (p
      < 0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis
      by 2.3 years, potentially allowing earlier clinical intervention. In pancreatic
      secretions, a combination of K-ras and Her-2/neu when appropriately standardized
      can be diagnostic in 75 % of PDA. CONCLUSIONS: Our study suggests that Adnab-9
      may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be
      reflective of the presence of Paneth cells confirmed by Defensin-5 staining.
      These cells may modulate the biological activity of the cancer and confer a
      better prognosis.

PMID- 23001407
TI  - miR-17-5p inhibitor enhances chemosensitivity to gemcitabine via upregulating Bim
      expression in pancreatic cancer cells.
AB  - BACKGROUND: miR-17-5p is reported to be overexpressed in pancreatic cancer, and
      it plays an important role in carcinogenesis and cancer progression. Gemcitabine
      is the standard first-line chemotherapeutic agent for pancreatic cancer, however
      the chemoresistance limits the curative effect. AIMS: In the present study, we
      investigated whether inhibition of miR-17-5p could enhance chemosensitivity to
      gemcitabine in pancreatic cancer cells. METHODS: miR-17-5p inhibitor was
      transfected to pancreatic cancer cell lines Panc-1 and BxPC3, and then cell
      proliferation, cell apoptosis, caspase-3 activation, and chemosensitivity to
      gemcitabine were measured in vitro. RESULTS: Our data showed that Panc-1 and
      BxPC3 cells transfected with miR-17-5p inhibitor showed growth inhibition,
      spontaneous apoptosis, higher caspase-3 activation, and increased
      chemosensitivity to gemcitabine. In addition, miR-17-5p inhibitor upregulated Bim
      protein expression in a dose-dependent manner without changing the Bim mRNA
      level, and it increased the activity of a luciferase reporter construct
      containing the Bim-3' untranslated region. CONCLUSIONS: These results prove that
      miR-17-5p negatively regulates Bim at the posttranscriptional level. We suggest
      that miR-17-5p inhibitor gene therapy would be a novel approach to
      chemosensitization for human pancreatic cancer.

PMID- 23001408
TI  - May the truth be with you: lubiprostone as EP receptor agonist/ClC-2
      internalizing "inhibitor".

PMID- 23001409
TI  - How are immigrant background and gender associated with the utilisation of
      psychiatric care among adolescents?
AB  - PURPOSE: To investigate how parental country of birth and individual gender
      affect utilisation of psychiatric care in adolescents. METHODS: On the basis of
      data from the Longitudinal Multilevel Analysis in Scania database, the article
      employs logistic regression to analyse the utilisation of psychiatric care among
      adolescents aged 13-18 (n = 92203) who were living in the southern Swedish county
      of Scania in 2005. RESULTS: Adolescents whose parents were born in middle- or low
      income countries presented lower levels of psychiatric outpatient care
      utilisation than those with native parents. Initially, no associations were found
      between the utilisation of psychiatric inpatient care and parental country of
      birth. Following adjustment for socio-demographic variables, it was found that
      adolescents with parents born in low-income countries were less likely to utilise
      psychiatric inpatient care. Girls presented higher levels of psychiatric care
      utilisation, but controls for possible interactions revealed that this was true
      primarily for girls with parents born in Sweden or other high-income countries.
      CONCLUSIONS: The different utilisation patterns found among adolescents with
      different backgrounds should be taken into consideration when planning and
      designing psychiatric care for adolescents, and when allocating resources. Our
      results may indicate lower levels of mental health problems among adolescents
      with parents born in middle- or low-income countries implying that protective
      factors compensate other stressors implicated in mental health problems. On the
      other hand, our findings may indicate an unmet health-care need as a result of
      problems accessing care.

PMID- 23001411
TI  - Emotions and cognitions as correlates of early adolescent sexual behavior among
      Dominican youth in the United States and Dominican Republic.
AB  - The present study examined cognitive and emotional correlates of sexual decision
      making among three groups of Dominican adolescents: (a) Dominican youth who were
      born and raised in New York City, (b) Dominican youth who recently immigrated to
      New York City from the Dominican Republic, and (c) Dominican adolescents who were
      born and currently reside in the Dominican Republic. Data were collected via self
      administered questionnaires from Dominican mother-adolescent dyads in New York
      City (n = 1,008) and the Dominican Republic (n = 213). Across groups, positive
      emotion constructs were consistently among the most important correlates of
      intentions to engage in sexual intercourse while issues related to STIs and HIV
      showed the lowest correlations. Interestingly, positive correlations with
      intentions to engage in intercourse were found among Dominican-residing males, as
      were positive correlations with intentions among Dominican-residing females. The
      implications for HIV prevention programs for Dominican youth are discussed.

PMID- 23001412
TI  - HIV-negative and HIV-positive gay men's attitudes to medicines, HIV treatments
      and antiretroviral-based prevention.
AB  - We assessed attitudes to medicines, HIV treatments and antiretroviral-based
      prevention in a national, online survey of 1,041 Australian gay men (88.3% HIV
      negative and 11.7% HIV-positive). Multivariate analysis of variance was used to
      identify the effect of HIV status on attitudes. HIV-negative men disagreed with
      the idea that HIV drugs should be restricted to HIV-positive people. HIV-positive
      men agreed and HIV-negative men disagreed that taking HIV treatments was
      straightforward and HIV-negative men were more sceptical about whether HIV
      treatment or an undetectable viral load prevented HIV transmission. HIV-negative
      and HIV-positive men had similar attitudes to pre-exposure prophylaxis but
      divergent views about 'treatment as prevention'.

PMID- 23001410
TI  - Post-transplantation B cell function in different molecular types of SCID.
AB  - PURPOSE: Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic
      cause characterized by profound deficiencies of T, B and sometimes NK cell
      function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical
      parental bone marrow transplantation (BMT) results in thymus-dependent
      genetically donor T cell development in the recipients, leading to a high rate of
      long-term survival. However, the development of B cell function has been more
      problematic. We report here results of analyses of B cell function in 125 SCID
      recipients prior to and long-term after non-ablative BMT, according to their
      molecular type. METHODS: Studies included blood immunoglobulin measurements;
      antibody titers to standard vaccines, blood group antigens and bacteriophage Phi
      X 174; flow cytometry to examine for markers of immaturity, memory, switched
      memory B cells and BAFF receptor expression; B cell chimerism; B cell
      spectratyping; and B cell proliferation. RESULTS: The results showed that B cell
      chimerism was not required for normal B cell function in IL7Ralpha-Def, ADA-Def
      and CD3-Def SCIDs. In X-linked-SCID, Jak3-Def SCID and those with V-D-J
      recombination defects, donor B cell chimerism was necessary for B cell function
      to develop. CONCLUSION: The most important factor determining whether B cell
      function develops in SCID T cell chimeras is the underlying molecular defect. In
      some types, host B cells function normally. In those molecular types where host B
      cell function did not develop, donor B cell chimerism was necessary to achieve B
      cell function. 236 words.

PMID- 23001413
TI  - Oral adherence monitoring using a breath test to supplement highly active
      antiretroviral therapy.
AB  - A breath-based adherence system to document ingestion of oral medications (e.g.,
      HAART) was investigated. Specifically, the food additive 2-butanol, which can be
      easily packaged with a drug, is converted via alcohol dehydrogenase to the
      volatile metabolite 2-butanone that rapidly appears in breath, indicating
      adherence. In healthy adults using a portable sensor and GC-MS, the following
      experiments were performed: yield of 2-butanone in breath following ingestion of
      2-butanol, adherence system accuracy, and potential interference of the adherence
      system by food or misplacement of 2-butanol on the tongue. During feasibility
      testing, every subject exhaled 2-butanone with 6.6 +/- 1.5 min to peak
      concentrations of 548 +/- 235 ppb following ingestion of 2-butanol (40 mg). ROC
      areas at 5 and 10 min were 0.95 (0.86-1.00) and 1.00 (1.00-1.00). Food did not
      interfere. Tongue application resulted in large concentrations of 2-butanol, but
      not 2-butanone. A breath test to provide definitive evidence of oral medication
      adherence appears technically feasible.

PMID- 23001414
TI  - Strength of round and uterosacral ligaments: a biomechanical study.
AB  - PURPOSE: To investigate the tensile biomechanical properties of round and
      uterosacral ligaments. METHODS: Tissue samples were obtained from 15 female
      cadavers without pelvic organ prolapse. Uniaxial tensile tests were performed to
      obtain stiffness and maximum stress of round and uterosacral ligaments.
      Correlations were calculated using the Pearson correlation coefficient.
      Statistical differences between groups were tested using Student's paired and
      unpaired t test. RESULTS: There was a great variability in the measurements of
      stiffness and maximum stress in pelvic ligaments. The round ligaments
      demonstrated stiffness of 9.1 +/- 1.6 MPa (mean +/- SEM) (ranging from 2 to 25.6
      MPa) and maximum stress of 4.3 +/- 0.7 MPa (ranging from 1.2 to 11.5 MPa). The
      stiffness of the uterosacral ligaments was 14.1 +/- 1.4 MPa (ranging from 5.7 to
      26.1 MPa) with maximum stress of 6.3 +/- 0.8 MPa (ranging from 2.2 to 11.9 MPa).
      There was a strong positive correlation between stiffness and maximum stress in
      female pelvic ligaments (rho = 0.851; p < 0.001). The uterosacral ligaments
      demonstrated higher stiffness and maximum stress compared to the round ligaments
      (p = 0.006 and p = 0.034; respectively). Age, body mass index and menopausal
      status were not associated with the biomechanical proprieties of round and
      uterosacral ligaments. Nulliparous women had lower uterosacral stiffness (15.5 +/
      1.3 vs. 10 +/- 1.8 MPa; p = 0.033) and maximum stress (8.2 +/- 0.9 vs. 4.2 +/-
      1.1 MPa; p = 0.028) compared to parous women. CONCLUSION: The uterosacral
      ligaments are significantly more resistant than round ligaments. Parturition
      seems to enhance the stiffness and maximum stress of the ligaments.

PMID- 23001415
TI  - CT-navigation versus fluoroscopy-guided placement of pedicle screws at the
      thoracolumbar spine: single center experience of 4,500 screws.
AB  - PURPOSE: Single center evaluation of the placement accuracy of thoracolumbar
      pedicle screws implanted either with fluoroscopy or under CT-navigation using 3D
      reconstruction and intraoperative computed tomography control of the screw
      position. There is in fact a huge variation in the reported placement accuracy of
      pedicle screws, especially concerning the screw placement under conventional
      fluoroscopy most notably due to the lack of the definition of screw misplacement,
      combined with a potpourri of postinstrumentation evaluation methods. METHODS: The
      operation data of 1,006 patients operated on in our clinic between 1995 and 2005
      is analyzed retrospectively. There were 2,422 screws placed with the help of CT
      navigation compared to 2,002 screws placed under fluoroscopy. The postoperative
      computed tomography images were reviewed by a radiologist and an independent
      spine surgeon. RESULTS: In the lumbar spine, the placement accuracy was 96.4 %
      for CT-navigated screws and 93.9 % for pedicle screws placed under fluoroscopy,
      respectively. This difference in accuracy was statistically significant (Fishers
      Exact Test, p = 0.001). The difference in accuracy became more impressing in the
      thoracic spine, with a placement accuracy of 95.5 % in the CT-navigation group,
      compared to 79.0 % accuracy in the fluoroscopy group (p < 0.001). CONCLUSION:
      This study underlines the relevance of CT-navigation-guided pedicle screw
      placement, especially when instrumentation of the middle and upper thoracic spine
      is carried out.

PMID- 23001417
TI  - Attentional shifts by gaze direction in voluntary orienting: evidence from a
      microsaccade study.
AB  - Shifts in spatial attention can be induced by the gaze direction of another.
      However, it is unclear whether gaze direction influences the allocation of
      attention by reflexive or voluntary orienting. The present study was designed to
      examine which type of attentional orienting is elicited by gaze direction. We
      conducted two experiments to answer this question. In Experiment 1, we used a
      modified Posner paradigm with gaze cues and measured microsaccades to index the
      allocation of attention. We found that microsaccade direction followed cue
      direction between 200 and 400 ms after gaze cues were presented. This is
      consistent with the latencies observed in other microsaccade studies in which
      voluntary orienting is manipulated, suggesting that gaze direction elicits
      voluntary orienting. However, Experiment 1 did not separate voluntary and
      reflexive orienting directionally, so in Experiment 2, we used an anticue task in
      which cue direction (direction to allocate attention) was the opposite of gaze
      direction (direction of gaze in depicted face). The results in Experiment 2 were
      consistent with those from Experiment 1. Microsaccade direction followed the cue
      direction, not gaze direction. Taken together, these results indicate that the
      shift in spatial attention elicited by gaze direction is voluntary orienting.

PMID- 23001418
TI  - Graphene on Si(111)7*7.
AB  - We demonstrate that it is possible to mechanically exfoliate graphene under
      ultrahigh vacuum conditions on the atomically well defined surface of single
      crystalline silicon. The flakes are several hundred nanometers in lateral size
      and their optical contrast is very faint, in agreement with calculated data.
      Single-layer graphene is investigated by Raman mapping. The graphene and 2D peaks
      are shifted and narrowed compared to undoped graphene. With spatially resolved
      Kelvin probe measurements we show that this is due to p-type doping with hole
      densities of n(h) ~/= 6 * 10(12) cm(-2). The in vacuo preparation technique
      presented here should open up new possibilities to influence the properties of
      graphene by introducing adsorbates in a controlled way.

PMID- 23001416
TI  - Pelvic joint fusions in patients with chronic pelvic girdle pain: a 23-year
      follow-up.
AB  - PURPOSE: Fusion of the sacroiliac joints (SIJ) has been a treatment option for
      patients with severe pelvic girdle pain (PGP). The primary aims were to evaluate
      the long-term outcomes in patients who underwent SIJ fusion and to compare 1-year
      outcomes with long-term outcomes. The secondary aim was to compare patients who
      underwent SIJ fusion with a comparable group who did not. METHODS: This study
      includes fifty patients that underwent SIJ fusion between 1977 and 1998. Function
      (the Oswestry disability index; ODI), pain intensity (visual analogue scale; VAS)
      and health-related quality of life (SF-36) were determined according to a patient
      reported questionnaire. The questionnaire scores were compared with previously
      recorded 1-year outcomes and with questionnaire scores from a group of 28
      patients who did not undergo SIJ fusion. RESULTS: The patients who underwent SIJ
      fusion reported a mean ODI of 33 (95 % CI 24-42) and a mean VAS score of 54 (95 %
      CI 46-63) 23 years (range 19-34) after surgery. Regarding quality of life, the
      patients reported reduced physical function, but mental health was not affected
      in the same manner. The patients with successful 1-year outcomes (48 %) retained
      significantly improved function and reduced pain levels compared with the
      subgroup of patients with unsuccessful 1-year outcomes (28 %). The patients who
      underwent surgery did not differ from the non-surgery group in any outcome at the
      long-term follow-up. CONCLUSIONS: Patients treated with SIJ fusion had moderate
      disability and pain 23 years after surgery, and the 1-year outcomes were
      sustained 23 years after surgery. Although many fused patients reported good
      outcome, this group did not differ from the comparable non-surgical group.

PMID- 23001419
TI  - Enhancement of anatomical structures and detection of metastatic cervical lymph
      nodes: comparison of two different contrast material doses.
AB  - PURPOSE: To determine if a 20 % reduction in the contrast material dose is
      acceptable in the CT evaluation of patients with head and neck malignancy.
      MATERIALS AND METHODS: Sixty consecutive patients (mean age 67 years) with head
      and neck malignancy underwent contrast-enhanced CT according to two different
      protocols: protocol A (80 mL of contrast material administered at an injection
      rate of 1.5 mL/s) and protocol B (100 mL at 1.9 mL/s). The enhancement of
      anatomical structures and detectability of metastatic nodes were compared between
      the two protocols. Pathologic analysis of the surgical resection served as the
      reference standard. RESULTS: CT numbers of the anatomical structures were not
      significantly different between the two protocols. Mean sensitivity (64 and 77 %
      for protocols A and B, respectively), specificity (78 and 84 %), and accuracy (74
      and 83 %) tended to be higher for protocol B than for A, but no significant
      difference was found. CONCLUSION: Reducing the contrast material dose by 20 % did
      not significantly impair the enhancement of anatomical structures or the
      detection of metastatic cervical lymph nodes. Radiologists should therefore
      consider reducing the contrast material dose used in head and neck CT.

PMID- 23001420
TI  - Diagnosis and management of ebstein anomaly of the tricuspid valve.
AB  - OPINION STATEMENT: Ebstein anomaly (EA) is a rare congenital heart defect that
      may not be detected until late in adolescence or adulthood. Since the original
      description in a 19-year-old laborer with severe tricuspid valve (TV)
      regurgitation in 1866, our understanding of this rare condition has increased to
      the recognition that it is an abnormality not only of the TV, but also of the
      right ventricle (RV). EA is the result of failure of delamination of the TV
      leaflets from the interventricular septum, resulting in adherence of the leaflets
      to the underlying myocardium. This results in a wide variety of abnormalities,
      including apical and posterior displacement of the dilated TV annulus; dilation
      of the "atrialized" portion of the RV; and fenestrations, redundancy, and
      tethering of the anterior leaflet of the TV. The malformed TV is usually
      regurgitant, but may rarely be stenotic. The clinical manifestations of EA in the
      adult depend on several factors, including the extent of TV leaflet distortion,
      degree of tricuspid regurgitation (TR), right atrial pressure, and presence of a
      right-to-left atrial level shunt. Over the past several decades, advances in
      diagnostic imaging and surgical techniques have contributed to our current
      management of this challenging congenital heart defect.

PMID- 23001421
TI  - Determination of bioaccumulation of heavy metals and selenium in tissues of brown
      trout Salmo trutta macrostigma (Dumeril, 1858) from Munzur Stream, Tunceli,
      Turkey.
AB  - The objective of the present work was to determine the bioaccumulation of arsenic
      (As), cadmium (Cd), copper (Cu), lead (Pb), mercury (Hg), uranium (U) and
      selenium (Se) in gill, liver, and muscle tissues of the fresh water fish Salmo
      trutta macrostigma (Dumeril, 1858) in Munzur Stream, Tunceli, Turkey. The highest
      concentrations of U (1.83 MUg kg(-1)), Pb (119.84 MUg kg(-1)) and Se (1.31 MUg
      kg(-1)) were recorded in the gills of S. t. macrostigma. Concentrations of As
      (46.27 MUg kg(-1)), Cd (109.19 MUg kg(-1)), Hg (16.40 MUg kg(-1)), Cu (18.19 MUg
      kg(-1)) were recorded at highest levels in the liver. The results showed that
      there were significant differences in concentrations of As, Cd, Cu, Pb, Se, U and
      Hg in gill, liver and muscle tissue (p < 0.05). Heavy metals were within the
      edible parts of the investigated fish were in the permissible safety levels for
      human uses.

PMID- 23001422
TI  - Increase in mitochondrial DNA copy number in response to ochratoxin A and
      methanol-induced mitochondrial DNA damage in Drosophila.
AB  - The current study examined the effects of ochratoxin A (OTA) and methanol on
      mitochondrial DNA (mtDNA). The results showed that methanol application caused
      approximately 29 % more damage than the control group, and that there were no
      significant differences among the other groups in terms of mtDNA damage. The
      application of 0.04 ng/mL OTA and 0.04 ng/mL OTA with methanol increased mtDNA
      copy number compared with the control and 0.005 ng/mL OTA with methanol groups.
      The copy number in the 0.04 ng/mL OTA group was approximately 16 % greater than
      in the control.

PMID- 23001423
TI  - Distribution and bioavailability of metals in subsidence land in a coal mine
      China.
AB  - Land subsidence in coal mine would change the type of soil so that it influences
      the distribution and bioavailability of metals. The results show that the total
      metal concentration was in the range from 0.41 +/- 0.26 mg/kg (Cd) to 94.16 +/-
      12.06 mg/kg (Zn) and Cd was the serious pollution metal. In spatial, the
      concentration of most metals (except Sb) was highest in perennial waterlogged
      zone while was lowest in no waterlogged zone, which implied that the perennial
      waterlogged zone was a sink of metals in coal mine area. However, the bio
      available fraction of metals was lowest in perennial waterlogged zone.

PMID- 23001424
TI  - The fate of Helicobacter pylori phagocytized by Acanthamoeba polyphaga
      demonstrated by fluorescent in situ hybridization and quantitative polymerization
      chain reaction tests.
AB  - Helicobacter pylori able to express green fluorescent protein, as well as an ATCC
      strain, and a clinical isolate of this pathogen were evaluated for their ability
      to survive predation by Acanthamoeba polyphaga. Ingestion was evaluated by
      microscopic observation of the GFP-H. pylori and BacLightTM-stained cells.
      Following phagocytosis, the fate of cells was assessed by fluorescent in situ
      hybridization with an oligonucleotide targeting H. pylori 16S rRNA and by
      quantitative-polymerase chain reaction (qPCR) tests with primers to 16S rDNA.
      Fluorescent in situ hybridization tests were inconclusive with only a small
      percentage of amoebae apparently containing active intracellular H. pylori.
      Furthermore, no increase in bacterial cells was detected by qPCR. Additional
      research is required to elucidate the mechanisms by which amoebae phagocytize
      this important bacterial pathogen.

PMID- 23001425
TI  - A combined use of autolysin p60 and listeriolysin O antigens induces high
      protective immune responses against Listeria monocytogenes infection.
AB  - Listeria monocytogenes is an intracellular bacterium responsible for listeriosis
      in both humans and animals. Infected livestock is believed to be one source of
      this pathogen. Vaccination is an optimal approach to control the occurrence of
      this disease in livestock. However, inactivated vaccines have been reported to be
      insufficient to offer immune protection against L. monocytogenes. Here we
      evaluated the immune protection capacity of a combination of recombinant p60 and
      LLO. Mice immunized with p60 and LLO generated a high level of anti-L.
      monocytogenes antibodies. In addition, the elevated levels of IFN-gamma and the
      decreased levels of IL-4 were also observed in these treated mice. Consistent
      with the colonization of L. monocytogenes post infection, all mice in the control
      group died within 5 days after infection of L. monocytogenes, while 40, 40, 80,
      and 100 % of animals immunized with inactivated L. monocytogenes vaccine (ILMV),
      LLO + ILMV, p60 + ILMV, and p60 + LLO + ILMV, respectively, survived for 2 weeks.
      Collectively, the results presented in this study demonstrate the capacity of a
      combination of LLO and p60 to elicit high protective immune responses against L.
      monocytogenes infection.

PMID- 23001426
TI  - Refining the phenotype associated with MEF2C point mutations.
AB  - Up to now, only five-point mutations in the MEF2C gene have been described in
      patients with severe mental retardation with absent speech, limited walking
      abilities, epilepsy, and lack of gross malformations. In brain, MEF2C is
      essential for early neurogenesis, neuronal migration, and differentiation. Here,
      we present a new patient with severe mental retardation, epilepsy, and hand
      stereotypies associated with a novel MEF2C frameshift mutation c.457delA. The
      purpose of this work was to clarify criteria for the selection of patients with
      severe intellectual disability to screen for deficiency in the MEF2C gene. By
      combining the clinical data of all patients with MEF2C point mutations published
      so far with the phenotype of our patient, a targeted search for MEF2C mutations
      could be applied to patients with a severe intellectual deficiency associated
      with absence of language and hypotonia, strabismus, and epilepsy (started after 6
      months, often well controlled by valproate).

PMID- 23001427
TI  - Evidence of species-specific detoxification processes for trace elements in
      shorebirds.
AB  - This study investigated sub-lethal effects and detoxification processes activated
      in free-ranging Red Knots (RKs) (Calidris canutus) from the Pertuis Charentais on
      the Atlantic coast of France, and compared the results with previous data
      obtained on another shorebird species, the Black-tailed Godwit (Limosa limosa).
      The concentrations of 13 trace elements (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni,
      Pb, Se, Zn) were assessed in the liver, kidneys, muscle and feathers. Stable
      isotope analyses of carbon and nitrogen were carried out to determine whether
      differences in diet explained variations in elemental uptake. The mRNA expression
      of relevant genes (cytochrome c oxidase 1, acetyl-CoA carboxylase, Cu/Zn and Mn
      superoxide dismutase, catalase, metallothionein, malic enzyme), antioxidant
      enzyme activities (catalase, glutathione peroxidase (GPx), superoxide dismutase),
      and metallothionein (MT) levels were investigated to shed light on trace element
      detoxification and toxic effects. Although Red Knots were characterized by
      elevated As and Se concentrations which were potentially toxic, most elements
      were usually below toxicity threshold levels. The results strongly suggested a
      dietary specialization of Red Knots, with individuals feeding on higher trophic
      status prey experiencing higher As, Hg and Se burdens. Red Knots and Godwits also
      showed discrepancies in elemental accumulation and detoxification processes.
      Higher As and Se concentrations in Red Knots enhanced catalase gene expression
      and enzyme activity, while Godwits had higher Ag, Cu, Fe and Zn levels and showed
      higher MT production and GPx activity. The results strongly suggest that
      detoxification pathways are essentially trace element- and species-specific.

PMID- 23001428
TI  - Chronic toxicity of tire and road wear particles to water- and sediment-dwelling
      organisms.
AB  - Tire and road wear particles (TRWP) consist of a complex mixture of rubber, and
      pavement released from tires during use on road surfaces. Subsequent transport of
      the TRWP into freshwater sediments has raised some concern about the potential
      adverse effects on aquatic organisms. Previous studies have shown some potential
      for toxicity for tread particles, however, toxicity studies of TRWP collected
      from a road simulator system revealed no acute toxicity to green algae, daphnids,
      or fathead minnows at concentrations up to 10,000 mg/kg under conditions
      representative of receiving water bodies. In this study, the chronic toxicity of
      TRWP was evaluated in four aquatic species. Test animals were exposed to whole
      sediment spiked with TRWP at concentrations up to 10,000 mg/kg sediment or
      elutriates from spiked sediment. Exposure to TRWP spiked sediment caused mild
      growth inhibition in Chironomus dilutus but had no adverse effect on growth or
      reproduction in Hyalella azteca. Exposure to TRWP elutriates resulted in slightly
      diminished survival in larval Pimephales promelas but had no adverse effect on
      growth or reproduction in Ceriodaphnia dubia. No other endpoints in these species
      were affected. These results, together with previous studies demonstrating no
      acute toxicity of TRWP, indicate that under typical exposure conditions TRWP in
      sediments pose a low risk of toxicity to aquatic organisms.

PMID- 23001430
TI  - Ionic liquid-in-ionic liquid nanoemulsions.
AB  - A new type of nanoemulsion formed by two immiscible ionic liquids was prepared
      for the first time. This novel kind of emulsion involves no volatile organic
      solvent. Metal-organic framework nanorods with large mesopores were synthesized
      in the nanoemulsion.

PMID- 23001429
TI  - Comparison of Forster-resonance-energy-transfer acceptors for tryptophan and
      tyrosine residues in native proteins as donors.
AB  - Homogenous bioaffinity analysis with tryptophan/tyrosine residues in native
      proteins as FOrster-resonance-energy-transfer (FRET) donors is feasible when
      suitable fluorophors can act as FRET acceptors in ligands (FRET probes) and FRET
      efficiency in complexes of proteins and FRET probes is high enough. In complexes
      of proteins and FRET probes, suitable acceptors should have excitation peaks
      around 335 nm and high rotation freedom, are preferred to have sufficient quantum
      yields and excitation valleys around 280 nm. In protein binding sites mimicked
      with mixtures of neutral phosphate buffer and organic solvents, quantum yields of
      candidate acceptors are altered inconsistently but their excitation peaks show
      tiny changes. Fluorophores as acceptors in such FRET probes are buried inside
      glutathione-S-transferase and have low rotation freedom, but are localized on
      streptavidin surface and display high rotation freedom; FRET efficiency in
      complexes of streptavidin and its FRET probes is much stronger than that in
      complexes of glutathione-S-transferase and its FRET probes. Specially, the
      quantum yield is about 0.70 for free 1-naphthylamine probe in neutral phosphate
      buffer, about 0.50 for 1-naphthylamine probe bound by streptavidin, and about
      0.15 for that bound by glutathione-S-transferase. The quantum yield is about 0.06
      for free dansylamide probe, about 0.11 for dansylamide probe bound by
      streptavidin and about 0.27 for that bound by glutathione-S-transferase.
      Therefore, 1-naphthylamine and dansylamide are effective acceptors when they
      localize on surfaces of complexes of proteins and FRET probes.

PMID- 23001431
TI  - Albirhodobacter marinus gen. nov., sp. nov., a member of the family
      Rhodobacteraceae isolated from sea shore water of Visakhapatnam, India.
AB  - A novel marine, Gram-negative, rod-shaped bacterium, designated strain N9(T), was
      isolated from a water sample of the sea shore at Visakhapatnam, Andhra Pradesh
      (India). Strain N9(T) was found to be positive for oxidase and catalase
      activities. The fatty acids were found to be dominated by C(16:0), C(18:1)
      omega7c and summed in feature 3 (C(16:1) omega7c and/or C(16:1) omega6c). Strain
      N9(T) was determined to contain Q-10 as the major respiratory quinone and
      phosphatidylethanolamine, phosphatidylglycerol, two aminophospholipids, two
      phospholipids and four unidentified lipids as polar lipids. The DNA G+C content
      of the strain N9(T) was found to be 63 mol%. 16S rRNA gene sequence analysis
      indicated that Rhodobacter sphaeroides, Rhodobacter johrii, Pseudorhodobacter
      ferrugineus, Rhodobacter azotoformans, Rhodobacter ovatus and Pseudorhodobacter
      aquimaris were the nearest phylogenetic neighbours, with pair-wise sequence
      similarities of 95.43, 95.36, 94.24, 95.31, 95.60 and 94.74 %, respectively.
      Phylogenetic analysis showed that strain N9(T) formed a distinct branch within
      the family Rhodobacteraceae and clustered with the clade comprising species of
      the genus Pseudorhodobacter, together with species of the genera Roseicitreum,
      Roseinatronobacter, Roseibaca and Rhodobaca. Species of the genus
      Pseudorhodobacter are phylogenetically close with a 16S rRNA gene sequence
      dissimilarity of 5.9-7.3 % (92.7-94.1 % similarity). Based on the above-mentioned
      phenotypic characteristics and on phylogenetic inference, strain N9(T) is
      proposed as a representative of a new genus and a novel species of the family
      Rhodobacteraceae as Albirhodobacter marinus gen. nov., sp. nov. The type strain
      of Albirhodobacter marinus is N9 (= MTCC 11277(T) = JCM 17680(T)).

PMID- 23001432
TI  - The effect of humic acid on uranyl sorption onto bentonite at trace uranium
      levels.
AB  - The effect of humic acid (HA) on U(VI) sorption on bentonite was studied in batch
      experiments at room temperature and ambient atmosphere at a (237)U(VI)
      concentration of 8.4 * 10(-11) M and HA concentration of 100 mg L(-1). The
      distribution of U(VI) between the liquid and solid phases was studied as a
      function of pH and ionic strength both in the absence and presence of HA. It was
      shown that the uranyl sorption on bentonite is strongly dependent on pH and the
      presence of humics, and the effect of the addition order was negligible. In the
      absence of HA an enhancement in the uptake with increasing pH was observed and a
      sharp sorption edge was found to take place between pH 3.2 and 4.2. The presence
      of HA slightly increases uranium(VI) sorption at low pH and curtails it at
      moderate pH, compared to the absence of HA. In the basic pH range for both the
      presence and absence of HA the sorption of uranium is significantly reduced,
      which could be attributed to the formation of soluble uranyl carbonate complexes.
      The influence of ionic strength on U(VI) and HA uptake by bentonite were
      investigated in the range of 0.01-1.0 M, and while there was an enhancement in
      the sorption of humic acid with increasing ionic strength, no significant effect
      of the ionic strength on the U(VI) sorption was observed in both the absence and
      presence of HA.

PMID- 23001433
TI  - Ondansetron in patients with tinnitus: randomized double-blind placebo-controlled
      study.
AB  - The aim of this study was to assess the effect of ondansetron on symptoms of
      patients with subjective tinnitus accompanied by sensorineural hearing loss or
      normal hearing. Sixty patients with a chief complaint of tinnitus (with duration
      of more than 3 months) were equally randomized to ondansetron or placebo for 4
      weeks. The dose of ondansetron was gradually increased from 4 mg/day (one tablet)
      to 16 mg/day (4 tablets) during 12 days and then continued up to 4 weeks. The
      exact number of tablets was prescribed in the placebo group. Patients underwent
      audiologic examinations and filled questionnaires at baseline and after 4 weeks
      of treatment. Our primary outcomes were changes in Tinnitus Handicap Inventory
      questionnaire (THI), Tinnitus Severity Index (TSI) and visual analog scale (VAS)
      scores. Our secondary outcomes were the changes in depression and anxiety based
      on Hospital Anxiety and Depression (HADS) questionnaire, side effects, tinnitus
      loudness matching, tinnitus pitch matching, pure tone audiometry and speech
      recognition threshold (SRT). In the ondansetron and placebo groups, 27 and 26
      patients completed the study, respectively. The changes in VAS (P = 0.934), THI
      (P = 0.776), anxiety (P = 0.313) and depression (P = 0.163) scores were not
      different between the groups. TSI score decreased significantly in the
      ondansetron compared with the placebo group (P = 0.004). Changes in tinnitus
      loudness matching (P = 0.75) and pitch matching (P = 0.56) did not differ between
      the two groups. Ondansetron, but not placebo, decreased the SRT threshold (right,
      P < 0.001; left, P = 0.043) and mean PTA (right, P = 0.006; left, P < 0.001). In
      conclusion, ondansetron reduces the severity of tinnitus hypothetically through
      cochlear amplification.

PMID- 23001434
TI  - Protective effects of resveratrol on cisplatin-dependent inner-ear damage in
      rats.
AB  - Cisplatin is a common chemotherapeutic agent used in many solid and hematologic
      malignancies. The main unwanted effect of cisplatin is ototoxicity, for which no
      standard treatment has been reported. The present study examined the protective
      efficacy of resveratrol on cisplatin-dependent ototoxicity through an
      experimental model. Fifteen rats were randomized into three groups. Group 1
      (control group) (n = 5) received intraperitoneal (i.p.) 15 mg/kg cisplatin; group
      2 (resveratrol group) (n = 5) received i.p. 100 mg/kg resveratrol, followed by
      i.p. 15 mg/kg cisplatin; group 3 (n = 5) served as a vehicle group and received
      i.p. 1 ml dimethyl sulfoxide. All rats underwent the auditory brainstem response
      (ABR) test before and 72 h after the treatment. Pretreatment ABR values of the
      groups were not significantly different. The pretreatment hearing threshold
      values of the groups were 30 +/- 6.60 and 28.5 +/- 5.29 dB in groups 1 and 2,
      respectively (p > 0.05). The post-ABR-I and post-ABR-IV values were,
      respectively, 1.41 +/- 0.18 and 5.83 +/- 0.16 ms in the control subjects and 1.19
      +/- 0.22 and 4.58 +/- 0.27 ms in the study group. The ABR-I and ABR-IV durations
      in rats treated with resveratrol were significantly shorter (p < 0.01). A
      comparison of threshold values shows that the resveratrol-treated rats had
      significantly lower values than the control rats. After cisplatin injection, ABR
      I-IV intervals were compared among the groups. The ABR I-IV interval duration was
      4.42 +/- 0.16 ms in the control group, while the resveratrol-treated rats showed
      a significantly shorter ABR I-IV interval duration of 3.49 +/- 0.27 ms (p <
      0.001). Resveratrol attenuated cisplatin-dependent inner-ear damage, as shown by
      the ABR-I, ABR-IV, ABR I-IV interval, and hearing threshold values. Our results
      suggest that this natural antioxidant may be effectively used in reducing the
      unwanted effects of cisplatin on the ear physiology of patients, particularly
      those undergoing chemotherapy.

PMID- 23001435
TI  - Predictive factors for prolonged hospital stay in pediatric tonsillectomy
      patients.
AB  - OBJECTIVE: To determine factors that may potentially predict a prolonged hospital
      stay after scheduled tonsillectomy in the pediatric population. STUDY DESIGN:
      Retrospective chart review. SUBJECTS AND METHODS: A review of pediatric patients
      who had undergone a tonsillectomy at a tertiary medical center from July 2007 to
      November 2010 was made. Preoperative variables were analyzed to determine
      predictors of prolonged hospital stay (defined as >24 h) that may have influenced
      their length of stay. SETTING: Tertiary care medical center. RESULTS: 827 patient
      charts were reviewed. One hundred and one patients (12.2 %) had hospital stays
      >24 h. Indications for tonsillectomy included obstructive sleep apnea (69.2 %),
      tonsillitis (13.8 %), and tonsillar asymmetry (0.9 %). Seventy-seven (76.2 %)
      patients of the extended stay group had a delayed discharge because of poor oral
      intake. Fever and respiratory complications accounted for 0.5 and 1.8 %
      respectively of those patients who had extended stays. Patients with extended
      stays were younger (p < 0.001) and weighed less (p < 0.001). Patients with a
      history of sickle cell crises, reactive airway disease, bronchodilator use, and
      anti-reflux medication use (p < 0.05) were more likely to have a prolonged
      hospital stay. CONCLUSION: Factors from the history and physical of pediatric
      patients may predict which children are at higher risk for extended hospital
      stays after routine tonsillectomy. Predictors of extended stays include those
      under the age of four and children weighing <20 kg, those with a history of
      sickle cell crises or reactive airway disease, and those using bronchodilators or
      anti-reflux medication.

PMID- 23001436
TI  - Glucosinolate variation in leaves of Brassica rapa crops.
AB  - Total and individual glucosinolate (GSL) content of leaves of vegetable turnip
      rape (Brassica rapa L. var. rapa) was determined in a set of 45 varieties
      consisting in early, medium and late types grown at two locations in northwestern
      Spain. The objectives were to determine the diversity among varieties in GSL
      content and to relate that variation with earliness and plant habit. Eight GSL
      were identified, being two aliphatic GSL, gluconapin (84.4 % of the total GSL)
      and glucobrassicanapin (7.2 % of the total GSL) the most abundant. Indolic and
      aromatic GSL content were low but also showed significant differences among
      varieties. Differences in total and individual GSL content were found among
      varieties, plant habit groups, and earliness groups. Total GSL content ranged
      from 19 to 37.3 MUmol g(-1) dw in early and extra-late groups, respectively, and
      from 19.5 to 36.3 MUmol g(-1) dw for turnips and turnip greens groups,
      respectively. These differences were consistent to values found for gluconapin
      content where the turnip group had the highest values (31.8 MUmol g(-1) dw) and
      the turnip top group had the lowest (15.7 MUmol g(-1) dw). Two varieties, MBG
      BRS0429 and MBG-BRS0550 (from turnip greens and extra-late groups) and MBG
      BRS0438 (from turnips and late groups), stood out as they had the highest total
      GSL content and could be used as a good source of these beneficial bioactive
      compounds. Elucidation of genetic diversity among crops can provide useful
      information to assist plant breeders to design improved breeding strategies in
      order to obtain varieties rich on GSL.

PMID- 23001438
TI  - Contributions of sunlight and diet to vitamin D status.
AB  - Vitamin D is made in the skin using ultraviolet radiation of specific low
      wavelength, 290-315 nm (UVB). For many parts of the world there is a period when
      there is insufficient intensity of UVB to make vitamin D, which is reflected by a
      clear seasonal variation in vitamin D status. Sun avoidance practices, melanin in
      pigmented skin, and sun protection creams (sunscreen), if used properly, can
      dramatically reduce vitamin D synthesis. Few foods naturally contain vitamin D,
      although some countries fortify foods with vitamin D. Regulatory mechanisms in
      the skin mean there is no danger of vitamin D toxicity through sunlight
      synthesis. Although oral vitamin D is potentially toxic with high-dose
      supplements, there is a wide safety margin. Long-term safety data covering a
      range of potential adverse outcomes are limited.

PMID- 23001437
TI  - Identifying patients with severe sepsis using administrative claims: patient
      level validation of the angus implementation of the international consensus
      conference definition of severe sepsis.
AB  - BACKGROUND: Severe sepsis is a common and costly problem. Although consistently
      defined clinically by consensus conference since 1991, there have been several
      different implementations of the severe sepsis definition using ICD-9-CM codes
      for research. We conducted a single center, patient-level validation of 1 common
      implementation of the severe sepsis definition, the so-called "Angus"
      implementation. METHODS: Administrative claims for all hospitalizations for
      patients initially admitted to general medical services from an academic medical
      center in 2009-2010 were reviewed. On the basis of ICD-9-CM codes,
      hospitalizations were sampled for review by 3 internal medicine-trained
      hospitalists. Chart reviews were conducted with a structured instrument, and the
      gold standard was the hospitalists' summary clinical judgment on whether the
      patient had severe sepsis. RESULTS: Three thousand one hundred forty-six (13.5%)
      hospitalizations met ICD-9-CM criteria for severe sepsis by the Angus
      implementation (Angus-positive) and 20,142 (86.5%) were Angus-negative. Chart
      reviews were performed for 92 randomly selected Angus-positive and 19 randomly
      selected Angus-negative hospitalizations. Reviewers had a kappa of 0.70. The
      Angus implementation's positive predictive value was 70.7% [95% confidence
      interval (CI): 51.2%, 90.5%]. The negative predictive value was 91.5% (95% CI:
      79.0%, 100%). The sensitivity was 50.4% (95% CI: 14.8%, 85.7%). Specificity was
      96.3% (95% CI: 92.4%, 100%). Two alternative ICD-9-CM implementations had high
      positive predictive values but sensitivities of <20%. CONCLUSIONS: The Angus
      implementation of the international consensus conference definition of severe
      sepsis offers a reasonable but imperfect approach to identifying patients with
      severe sepsis when compared with a gold standard of structured review of the
      medical chart by trained hospitalists.

PMID- 23001439
TI  - Hypophosphatemic rickets: unraveling the role of FGF23.
AB  - The classification of the various forms of hypophosphatemic rickets has been
      rationalized by the discovery of the central role that fibroblast growth factor
      23 (FGF23) plays in the pathogenesis of a number of genetic and acquired forms of
      the disease. Although the details of the interaction of FGF23 with other
      osteoblast/osteocyte-derived proteins remain unclear at present, the measurement
      of circulating levels of FGF23 appears to be a useful biochemical test in
      determining the various causes of hypophosphatemic rickets. Furthermore, animal
      studies suggest that agents interfering in the action of FGF23 might play
      important roles in the future management of the FGF23-mediated forms of rickets.
      Phase 1 and phase 2 trials in humans with X-linked hypophosphatemic rickets are
      currently under way.

PMID- 23001441
TI  - Sperm crisis: what crisis?

PMID- 23001440
TI  - What do most erectile dysfunction guidelines have in common? No evidence-based
      discussion or recommendation of heart-healthy lifestyle changes and/or Panax
      ginseng.
AB  - Sexual health or erectile dysfunction (ED) state of the art guidelines provide a
      thorough overview of conventional prescription or other notable extrinsic
      treatment options. Yet, over the past 10-15 years, a plethora of international
      researchers have established that individual and comprehensive lifestyle changes
      can prevent and potentially improve ED. We review the lifestyle evidence that
      should equate to grade A or level 1 evidence recommendations for ED. We also
      review the evidence for Panax ginseng, an over-the-counter (OTC) dietary
      supplement with a 35-year history of laboratory investigations, multiple positive
      randomized trials over approximately 15 years and several independent meta
      analyses and systematic reviews. Perhaps it is time to at least discuss and even
      emphasize lifestyle and other non-conventional interventions in ED guidelines so
      that patients can explore a diversity of potentially synergistic choices with
      their physicians and can improve their quality and quantity of life. Ignoring the
      consistent, positive data on lifestyle modifications in ED guidelines, for
      example, is tantamount to ignoring diet and lifestyle changes to reduce the risk
      of or ameliorate cardiovascular diseases.

PMID- 23001442
TI  - Endocrine disruptors and falling sperm counts: lessons learned or not!

PMID- 23001444
TI  - Electromagnetic pollution: another risk factor for infertility, or a red herring?

PMID- 23001443
TI  - Mechanism of sperm capacitation and the acrosome reaction: role of protein
      kinases.
AB  - Mammalian sperm must undergo a series of biochemical and physiological
      modifications, collectively called capacitation, in the female reproductive tract
      prior to the acrosome reaction (AR). The mechanisms of these modifications are
      not well characterized though protein kinases were shown to be involved in the
      regulation of intracellular Ca(2+) during both capacitation and the AR. In the
      present review, we summarize some of the signaling events that are involved in
      capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase
      (PI3K) is phosphorylated/activated via a protein kinase A (PKA)-dependent
      cascade, and downregulated by protein kinase C alpha (PKCalpha). PKCalpha is
      active at the beginning of capacitation, resulting in PI3K inactivation. During
      capacitation, PKCalpha as well as PP1gamma2 is degraded by a PKA-dependent
      mechanism, allowing the activation of PI3K. The activation of PKA during
      capacitation depends mainly on cyclic adenosine monophosphate (cAMP) produced by
      the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads
      to an increase in actin polymerization, an essential process for the development
      of hyperactivated motility, which is necessary for successful fertilization.
      Actin polymerization is mediated by PIP(2) in two ways: first, PIP(2) acts as a
      cofactor for phospholipase D (PLD) activation, and second, as a molecule that
      binds and inhibits actin-severing proteins such as gelsolin. Tyrosine
      phosphorylation of gelsolin during capacitation by Src family kinase (SFK) is
      also important for its inactivation. Prior to the AR, gelsolin is released from
      PIP(2) and undergoes dephosphorylation/activation, resulting in fast F-actin
      depolymerization, leading to the AR.

PMID- 23001445
TI  - Downregulation of cold-inducible RNA-binding protein activates mitogen-activated
      protein kinases and impairs spermatogenic function in mouse testes.
AB  - Cold-inducible RNA-binding protein (CIRP) is an RNA-binding protein that is
      expressed in normal testes and downregulated after heat stress caused by
      cryptorchidism, varicocele or environmental temperatures. The purpose of this
      study was to investigate the functions of CIRP in the testes. We employed RNAi
      technique to knock down the expression of CIRP in the testes, and performed
      haematoxylin and eosin staining to evaluate morphological changes following
      knockdown. Germ cell apoptosis was examined by terminal deoxynucleotidal
      transferase-mediated dUTP nick end labelling (TUNEL) assay, and mitogen-activated
      protein kinase (MAPK) signalling pathways were investigated by Western blotting
      to determine the possible mechanism of apoptosis. We found that using siRNA is a
      feasible and reliable method for knocking down gene expression in the testes.
      Compared to controls, the mean seminiferous tubule diameter (MSTD) and the
      thickness of the germ cell layers decreased following siRNA treatment, whereas
      the percentage of apoptotic seminiferous tubules increased. The p44/p42, p38 and
      SAPK/JNK MAPK pathways were activated after downregulation of CIRP. In
      conclusion, we discovered that downregulation of CIRP resulted in increased germ
      cell apoptosis, possibly via the activation of the p44/p42, p38 and SAPK/JNK MAPK
      pathways.

PMID- 23001446
TI  - Selective decontamination of the digestive tract: the mechanism of action is
      control of gut overgrowth.
AB  - PURPOSE: Gut overgrowth is the pathophysiological event in the critically ill
      requiring intensive care. In relation to the risk of developing a clinically
      important outcome, gut overgrowth is defined as >=10(5) potential pathogens
      including 'abnormal' aerobic Gram-negative bacilli (AGNB), 'normal' bacteria and
      yeasts, per mL of digestive tract secretion. Surveillance samples of throat and
      gut are the only samples to detect overgrowth. Gut overgrowth is the crucial
      event which precedes both primary and secondary endogenous infection, and a risk
      factor for the development of de novo resistance. Selective decontamination of
      the digestive tract (SDD) is an antimicrobial prophylaxis designed to control
      overgrowth. METHODS: There have been 65 randomised controlled trials of SDD in
      15,000 patients over 25 years and 11 meta-analyses, which are reviewed. RESULTS
      AND CONCLUSIONS: These trials demonstrate that the full SDD regimen using
      parenteral and enteral antimicrobials reduces lower airway infection by 72 %,
      blood stream infection by 37 %, and mortality by 29 %. Resistance is also
      controlled. Parenteral cefotaxime which reaches high salivary and biliary
      concentrations eradicates overgrowth of 'normal' bacteria such as Staphylococcus
      aureus in the throat. Enteral polyenes control 'normal' Candida species. Enteral
      polymyxin and tobramycin, eradicate, or prevent gut overgrowth of 'abnormal'
      AGNB. Enteral vancomycin controls overgrowth of 'abnormal' methicillin-resistant
      S. aureus. SDD controls overgrowth by achieving high antimicrobial concentrations
      effective against 'normal' and 'abnormal' potential pathogens rather than by
      selectivity.

PMID- 23001447
TI  - Renal Doppler to assess renal perfusion in the critically ill: a reappraisal.
AB  - PURPOSE: To describe the method and significance of Doppler-based resistive index
      (RI) and to provide an updated description of its interest with a special focus
      on the critically ill. METHODS: Review of selected studies on RI found in the
      PubMed, Ovid and Cochrane databases. Additional references were retrieved from
      the selected studies. RESULTS: An increasing body of evidence suggests that renal
      Doppler may help to assess perfusion of native or transplanted kidneys. In
      addition, recent studies suggest that it may be useful in critically ill
      patients. The RI is a parameter derived from Doppler examination that is
      calculated as follows: [Formula: see text]. Renal Doppler has proven to be
      valuable for assessing large arterial or venous abnormalities and has been
      suggested to assess renal perfusion and to predict acute kidney injury (AKI) in
      critically ill patients. However, numerous factors have been shown to influence
      renal Doppler and may constitute potential confounding factors. Moreover,
      experience with critically ill patients is scant and our understanding of factors
      influencing RI in this setting is limited. CONCLUSION: Doppler-based RI seems to
      be a promising tool in the critically ill to assess the risk of AKI, help in
      differentiating persistent from transient AKI, or assess changes in renal
      perfusion as consequences of therapeutic intervention. However, we still lack
      large, adequately powered studies in non-selected populations of patients before
      implementing this technique in clinical practice. In addition, the impact of
      several factors that may influence this parameter remains to be evaluated.

PMID- 23001448
TI  - Management of renal replacement therapy in ICU patients: an international survey.
AB  - PURPOSE: The optimal management of renal replacement therapy (RRT) in critically
      ill patients remains a matter of debate, although insights have arisen from
      recent large trials. Nonetheless, little is known about the current practices and
      beliefs of intensivists. The goal of this study was to record current practices
      in RRT management among an international panel of intensivists. METHODS: An
      online questionnaire that included questions about RRT management in critically
      ill patients with acute kidney injury was sent to European Society of Intensive
      Care Medicine members in 2010. RESULTS: Two hundred and seventy-three
      intensivists from 50 countries responded. The respondents had an average of 12 (7
      20) years of experience in ICUs, and most of them worked in mixed ICUs. Most of
      the intensivists were responsible for prescribing RRT (92.6 %). Half of the
      respondents reported using both intermittent haemodialysis and continuous renal
      replacement therapy techniques (CRRT), but most preferred using CRRT. The reasons
      for preferring CRRT were the perception of better haemodynamic stability, better
      therapeutic effect resulting from cytokine removal and easier fluid balance
      control. The intensivists used higher RRT doses in septic patients than in non
      septic patients (p = 0.03). Finally, we observed an increasing inclination
      towards the early use of RRT among the intensivists. CONCLUSION: CRRT remains the
      preferred technique for most intensivists in Europe, and a large proportion of
      the participating intensivists used RRT prescription doses similar to those
      proposed a decade ago. Our results provide insights into the motivations of
      intensivists while presenting the technique that may help in selecting control
      groups for future trials.

PMID- 23001449
TI  - Is closed-suction drainage necessary after intradural primary spinal cord tumor
      surgery?
AB  - PURPOSE: The efficacy of closed-suction drainage in primary intradural spinal
      cord tumor surgery has not been addressed. We investigated whether closed-suction
      drainage is essential after primary intradural spinal cord tumor surgery.
      METHODS: From January 2003 to October 2011, 169 consecutive patients with primary
      intradural spinal cord tumors operated by a single surgeon were selected. Closed
      suction drainage was inserted in patients before August 2007, but was not used
      after August 2007. After removal of tumor and meticulous hemostasis, the opened
      dura was closed and made watertight using 4-0 silk with interrupt suture and 1.0
      cm(3) of surgical glue was applied in common. Closed-suction drainage was
      inserted below the muscular fascia in 75 patients (group I, M:F = 39:36; 46.20 +/
      15.63 years) and was not inserted in 94 patients (group II, M:F = 46:48; 51.05
      +/- 14.89 years). RESULTS: Neurological deficit precluding ambulation did not
      occur in all patients. Between group I and II, there were no significant
      differences in body mass index (22.75 +/- 3.16 vs. 23.51 +/- 3.22 kg/m(2); p =
      0.13), laminectomy level (2.45 +/- 1.46 vs. 2.33 +/- 1.91; p = 0.65), operation
      time (260.65 +/- 109.08 vs. 231.52 +/- 90.08 min; p = 0.06), estimated
      intraoperative blood loss (456.93 +/- 406.62 vs. 383.94 +/- 257.25 cm(3); p =
      0.18), and hospital stay period (9.25 +/- 5.01 vs. 9.35 +/- 5.75 days; p = 0.91).
      Two patients in group I underwent revision surgery due to wound problems, while
      revision surgery was not performed in group II (p = 0.20). CONCLUSION: Closed
      suction drainage may not be essential after primary intradural spinal cord tumor
      surgery.

PMID- 23001450
TI  - Risk factors for a poor outcome following surgical treatment of cervical
      spondylotic amyotrophy: a multicenter study.
AB  - INTRODUCTION: Cervical spondylotic amyotrophy (CSA) is characterized by muscle
      atrophy in the upper extremities without gait disturbance. However, the
      indications and outcomes of surgical treatment for CSA have not been clarified.
      The purpose of this study was to determine the risk factors for a poor outcome
      following surgical treatment of CSA. MATERIALS AND METHODS: We performed a
      retrospective review of CSA in patients from 1991 to 2010 through a multicenter
      study. We collected information regarding age, type of muscle atrophy,
      preoperative manual muscle test (MMT), duration of symptoms, high-intensity areas
      on T2-weighted MR images, low-intensity areas on T1-weighted MR images, levels of
      spinal canal stenosis, cervical kyphosis and surgical procedures (laminoplasty,
      anterior cervical discectomy and fusion and posterior spinal fusion), and
      calculated overall risk factors related to a poor outcome following surgery.
      Univariate analyses and multivariate logistic regression analysis were performed
      to identify correlates of a poor outcome. RESULTS: Fifty-nine patients, 95 % male
      (56 patients), were included in our analysis with a mean age of 59 years (range
      32-78 years). Eighteen patients did not improve after surgery. Symptom duration
      (OR = 1.263), preoperative MMT grade (OR = 0.169) and distal type of CSA (OR =
      9.223) were all associated with an increased risk of a poor surgical outcome.
      CONCLUSION: Early surgery is recommended for CSA patients in whom conservative
      treatment has not been successful. We also recommend surgery for patients who
      have severe preoperative muscle weakness or have the distal type of CSA.

PMID- 23001452
TI  - Interfractional trend analysis of dose differences based on 2D transit portal
      dosimetry.
AB  - Dose delivery of a radiotherapy treatment can be influenced by a number of
      factors. It has been demonstrated that the electronic portal imaging device
      (EPID) is valuable for transit portal dosimetry verification. Patient related
      dose differences can emerge at any time during treatment and can be categorized
      in two types: (1) systematic-appearing repeatedly, (2) random-appearing
      sporadically during treatment. The aim of this study is to investigate how
      systematic and random information appears in 2D transit dose distributions
      measured in the EPID plane over the entire course of a treatment and how this
      information can be used to examine interfractional trends, building toward a
      methodology to support adaptive radiotherapy. To create a trend overview of the
      interfractional changes in transit dose, the predicted portal dose for the
      different beams is compared to a measured portal dose using a gamma evaluation.
      For each beam of the delivered fraction, information is extracted from the gamma
      images to differentiate systematic from random dose delivery errors. From the
      systematic differences of a fraction for a projected anatomical structures,
      several metrics are extracted like percentage pixels with |gamma| > 1. We
      demonstrate for four example cases the trends and dose difference causes which
      can be detected with this method. Two sample prostate cases show the occurrence
      of a random and systematic difference and identify the organ that causes the
      difference. In a lung cancer case a trend is shown of a rapidly diminishing
      atelectasis (lung fluid) during the course of treatment, which was detected with
      this trend analysis method. The final example is a breast cancer case where we
      show the influence of set-up differences on the 2D transit dose. A method is
      presented based on 2D portal transit dosimetry to record dose changes throughout
      the course of treatment, and to allow trend analysis of dose discrepancies. We
      show in example cases that this method can identify the causes of dose delivery
      differences and that treatment adaptation can be triggered as a result. It
      provides an important element toward informed decision-making for adaptive
      radiotherapy.

PMID- 23001451
TI  - Clinical and radiological profile of ameloblastic fibro-odontoma: an update on an
      uncommon odontogenic tumor based on a critical analysis of 114 cases.
AB  - Ameloblastic fibro-odontoma is an uncommon benign tumor of the jaws that belongs
      to the group of mixed odontogenic tumors. The descriptions of its clinical and
      radiological features in the literature are not always accurate and sometimes
      even contradictory. The aim of the present study was to critically evaluate their
      clinical and radiological features as reported in the English-language
      literature. A total of 114 well-documented cases of ameloblastic fibro-odontomas
      (103 from publications and 11 of our own new cases) were analyzed. The patients'
      age ranged from 8 months to 26 years (mean 9.6). There were 74 (65 %) males, with
      a male-to-female ratio of 1.85:1 (P = 0.001). The mandible was involved in 74 (65
      %) cases, and the mandible-to-maxilla ratio was 1.85:1 (P < 0.001). Nearly 80 %
      of the lesions were located in the posterior region of the jaws, and most (58 %)
      were in the posterior mandible. Radiographically, most of the lesions were
      unilocular and only a few (~10 %) were multilocular. Most lesions were mixed
      radiolucent-radiopaque, and only a few (~5 %) were radiolucent. Almost all
      lesions (~92 %) were associated with the crown of an unerupted tooth/teeth. This
      comprehensive analysis of a large number of patients with an uncommon lesion
      revealed that ameloblastic fibro-odontomas are significantly more common in males
      and in the mandible, and that multilocular lesions are uncommon. It also revealed
      that, based on their clinical and radiological features, some of them are
      probably true neoplasms while others appear to be developing odontomas
      (hamartomas).

PMID- 23001454
TI  - An application of passive samplers to understand atmospheric mercury
      concentration and dry deposition spatial distributions.
AB  - Two modified passive samplers were evaluated at multiple field locations. The
      sampling rate (SR) of the modified polyurethane foam (PUF)-disk passive sampler
      for total gaseous mercury (TGM) using gold-coated quartz fiber filters (GcQFF)
      and gaseous oxidized mercury (GOM) using ion-exchange membranes (IEM) were 6.4 +/
      1.4 and 15.3 +/- 0.3 m(3) day(-1), respectively. The relative percent difference
      between TGM and GOM concentrations measured by a Tekran system and the passive
      samplers averaged 19 +/- 14 and 13 +/- 12% and ranged between 4-44 and 1.5-41%,
      respectively. The GcQFF and IEM substrates were also evaluated as collection
      media for surrogate surface dry deposition measurements. Mercury (Hg)
      concentration and dry deposition gradients were observed using these samplers at
      an urban/industrial site and compared to a rural/remote site. The Hg dry
      deposition rates measured by the surrogate surfaces were always higher than those
      calculated by a widely used inferential modeling method (1.3-50 fold). The Hg dry
      deposition measured at urban and suburban sites were comparable to those
      calculated from model. However, they were very different at a rural site,
      probably due to the low concentrations. Both methods are relatively low cost and
      will aid in understanding spatial distributions of Hg ambient air concentrations
      and dry deposition.

PMID- 23001453
TI  - Influence of CYP2C19 loss-of-function variants on the antiplatelet effects and
      cardiovascular events in clopidogrel-treated Chinese patients undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND AND OBJECTIVES: A large number of clinical studies have well
      demonstrated that the loss-of-function variant allele CYP2C19 2 is associated
      with attenuated response to clopidogrel and increased risk of developing stent
      thrombosis (ST) in white or black patients with stenting. However, similar
      association studies on the effect of the CYP2C19 2 and 3 variants on maximum
      platelet aggregation (MPA) and the risk of cardiovascular events are currently
      unavailable for the Chinese patients. This work was aimed at assessing the impact
      of the CYP2C19 2 and 3 variants on the antiplatelet effects and adverse
      cardiovascular events in clopidogrel-treated Chinese patients undergoing
      percutaneous coronary intervention (PCI). METHODS: The study population consisted
      of 617 patients undergoing PCI. Genotypes were determined using MALDI/TOF-MS. MPA
      was measured by light transmittance aggregometry. The clinical end-point was the
      1-year incidence of adverse cardiovascular events, including ST. RESULTS:
      Carriers of CYP2C19 heterozygous (1/2, or 1/3; n = 278) and mutant homozygous
      (2/2, 2/3, or 3/3, n = 80) genotypes had significantly higher MPA values than
      noncarriers (1/1; n = 259; P = 0.036 and 0.007 respectively). Moreover, the
      presence of the CYP2C19 2 or 3 mutant allele was significantly associated with an
      increased risk of developing ST, with the higher risk of ST being seen in
      patients homozygous for the CYP2C19 2 or 3 variant allele than in noncarriers
      (OR, 13.58; 95% CI, 1.49-123.31; P = 0.012). Furthermore, multivariate analysis
      revealed an independent association of the presence of CYP2C19*2 and/or 3 variant
      alleles with greater MPA values (P = 0.001) and increased risk of ST (OR, 11.67;
      95% CI, 1.21-78.83; P = 0.022). However, there was no significant influence of
      CYP2C19 2 and 3 on the risk of developing other adverse cardiovascular events.
      CONCLUSIONS: Carriage of the loss-of-function genetic variants CYP2C19 2 and 3 is
      significantly associated with attenuated platelet response to clopidogrel and an
      increased risk of ST in Chinese patients treated with stenting.

PMID- 23001455
TI  - Plant Oils and Cardiometabolic Risk Factors: The Role of Genetics.
AB  - More than 25 years have passed since Ancel Keys and others observed that high
      intake of monounsaturated fatty acids, especially as supplied by plants (eg,
      olive oil) was associated with lower cardiovascular and overall mortality. About
      15 years later, advances in genotyping technologies began to facilitate
      widespread study of relationships between dietary fats and genetic variants,
      illuminating the role of genetic variation in modulating human responses to fatty
      acids. More recently, microarray technologies evaluate the ways in which minor,
      bioactive compounds in plant oils (including olive, thyme, lemongrass, clove,
      eucalyptus, and others) alter gene expression to mediate anti-inflammatory and
      antioxidant effects. Results from a range of diverse technologies and approaches
      are coalescing to improve understanding of the role of the genome in shaping our
      responses to plant oils, and to clarify the genetic mechanisms underlying the
      cardioprotective benefits we derive from a wide range of plant oil constituents.

PMID- 23001456
TI  - The psychiatric interview: validity, structure, and subjectivity.
AB  - There is a glaring gap in the psychiatric literature concerning the nature of
      psychiatric symptoms and signs, and a corresponding lack of epistemological
      discussion of psycho-diagnostic interviewing. Contemporary clinical neuroscience
      heavily relies on the use of fully structured interviews that are historically
      rooted in logical positivism and behaviorism. These theoretical approaches marked
      decisively the so-called "operational revolution in psychiatry" leading to the
      creation of DSM-III. This paper attempts to examine the theoretical assumptions
      that underlie the use of a fully structured psychiatric interview. We address the
      ontological status of pathological experience, the notions of symptom, sign,
      prototype and Gestalt, and the necessary second-person processes which are
      involved in converting the patient's experience (originally lived in the first
      person perspective) into an "objective" (third person), actionable format, used
      for classification, treatment, and research. Our central thesis is that
      psychiatry targets the phenomena of consciousness, which, unlike somatic symptoms
      and signs, cannot be grasped on the analogy with material thing-like objects. We
      claim that in order to perform faithful distinctions in this particular domain,
      we need a more adequate approach, that is, an approach that is guided by
      phenomenologically informed considerations. Our theoretical discussion draws upon
      clinical examples derived from structured and semi-structured interviews. We
      conclude that fully structured interview is neither theoretically adequate nor
      practically valid in obtaining psycho-diagnostic information. Failure to address
      these basic issues may have contributed to the current state of malaise in the
      study of psychopathology.

PMID- 23001457
TI  - Potential for bias in the context of neuroethics. Commentary on "Neuroscience,
      neuropolitics and neuroethics: the complex case of crime, deception and fMRI".
AB  - Neuroscience research, like all science, is vulnerable to the influence of
      extraneous values in the practice of research, whether in research design or the
      selection, analysis and interpretation of data. This is particularly problematic
      for research into the biological mechanisms that underlie behavior, and
      especially the neurobiological underpinnings of moral development and ethical
      reasoning, decision-making and behavior, and the other elements of what is often
      called the neuroscience of ethics. The problem arises because neuroscientists,
      like most everyone, bring to their work assumptions, preconceptions and values
      and other sources of potentially inappropriate bias of which they may be unaware.
      It is important that the training of neuroscientists, and research practice
      itself, include open and in-depth discussion and examination of the assumptions
      that underlie research. Further, policy makers, journalists, and the general
      public, that is, the consumers of neuroscience research findings (and by
      extension, neurotechnologies) should be made aware of the limitations as well as
      the strengths of the science, the evolving nature of scientific understanding,
      and the often invisible values inherent in science.

PMID- 23001458
TI  - Marital sorting and parental wealth.
AB  - The extent of marital sorting by socioeconomic background has implications for
      the intergenerational transmission of inequality, the role of marriage as a
      mechanism for social mobility, and the extent of cross-group interactions within
      a society. However, studies of assortative mating have disproportionately focused
      on spouses' education, rather than their social origins. Using data from the
      Panel Study of Income Dynamics (PSID), and exploiting the unique genealogical
      design of the data set, we study the degree to which spouses sort on the basis of
      parental wealth. We find that the estimated correlation in parental wealth among
      married spouses, after controlling for race and age, is about .4. Importantly, we
      show that controlling for spousal education explains only one-quarter of sorting
      based on parental wealth. We show that our results are robust to accounting for
      measurement error in spousal reports of parental wealth and for selection into
      and out of marriage.

PMID- 23001459
TI  - Effects of Chai-Qin-Cheng-Qi decoction () on acute pancreatitis-associated lung
      injury in mice with acute necrotizing pancreatitis.
AB  - OBJECTIVE: To investigate the effects of Chai-Qin-Cheng-Qi Decoction (, CQCQD) on
      acute pancreatitis-associated lung injury in mice with acute necrotizing
      pancreatitis (ANP). METHODS: Thirty healthy mice were randomly divided into three
      groups: an ANP group (ANP+placebo, n=10); a treatment group (ANP+CQCQD, n=10);
      and a control group (normal mice+placebo, n=10). ANP was induced by
      intraperitoneal injection with 8% L-arginine (4 MUg/kg), and the control group
      was injected with normal saline. The treatment group received CQCQD (20 mL/kg),
      and the ANP and control groups received placebo (sucrose and starch)
      intragastrically at 2 h intervals. After the third intragastric administration,
      blood, pancreatic tissues and right lung tissues were collected for measurement
      of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) by enzyme-linked
      immunosorbent assay, and the expression of heat shock protein 70 (HSP70) in lung
      tissue was determined by Western blot analysis. Pathological changes of
      pancreatic tissue and lung tissue were examined. RESULTS: Serum IL-6 was
      significantly higher in the ANP group compared with the control and the treatment
      groups (1589.63+/-377.28 vs. 927.46+/-210.42 pg/mL, P<0.05, and 1589.63+/-377.28
      vs. 1107.73+/-351.62 pg/mL, P<0.05, respectively). The IL-10 concentration was
      significantly lower in the ANP group compared with the treatment group (920.64+/
      101.68 vs. 1177.84+/-201.72 pg/mL, P<0.05), but no signififi cant difference was
      found between the ANP and control groups and between the treatment and control
      groups. The expression level of HSP70 in the ANP and control groups was signififi
      cantly lower than in the treatment group (0.93+/-0.03 vs. 1.42+/-0.21, P<0.01,
      and 0.81+/-0.09 vs. 1.42+/-0.21, P<0.01, respectively). There was no signififi
      cant difference in HSP70 levels between the ANP and control groups. Histological
      scores of pancreatic and lung tissue were significantly decreased in the
      treatment group compared with the ANP groups (4.50+/-0.54 vs. 6.20+/-1.65,
      P<0.05, and 3.00+/-0.63 vs. 3.87+/-0.83, P<0.05, respectively). CONCLUSIONS: The
      incidence of acute pancreatitisassociated lung injury in ANP mice correlates
      positively with serum IL-6 concentration. CQCQD may inhibit IL-6 induction and
      increase IL-10 concentration and HSP70 expression, effectively reducing lung
      injury.

PMID- 23001460
TI  - Effects of serum containing Chinese medicine Sanpi Pingwei () formula on
      proliferation and apoptosis of human SGC-7901 cells.
AB  - OBJECTIVE: To investigate the effects of serum containing Chinese medicine (CM)
      Sanpi Pingwei (, SPPW) formula on the proliferation and apoptosis of human SGC
      7901 cells and the possible mechanism. METHODS: Serum containing CM SPPW formula
      (SPPW serum) was prepared by a serum pharmacology method. Human SGC-7901 cells
      were incubated with SPPW serum at three different concentrations and with the
      anticancer drug 5-fluorouracil (5-FU), respectively. Cell proliferation was
      assessed by MTT assay, and cell apoptosis was detected by flow cytometry assay.
      Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot assay
      were employed to confirm the expressions of Bcl-2, Bax and p53 in SGC-7901 cells
      at mRNA and protein levels, respectively. RESULTS: SPPW serum suppressed the
      proliferation of SGC-7901 cells in a time- and dose-dependent manner. The colony
      forming rate of negative control was 48.2%, while those in the three SPPW serum
      groups and the 5-FU group decreased significantly (P<0.01). The number of colony
      forming units in the SPPW high dosage group was significantly smaller than that
      in the 5-FU group (P<0.01). MTT assay showed that SPPW serum restrained the
      proliferation of SGC-7901 cells, and the inhibition rate increased significantly
      in a dose-dependent manner. Annexin V/PI Assay suggested that SPPW serum induced
      the apoptosis of SGC-7901 cells significantly. RT-PCR and western blot assay
      indicated that SPPW serum upregulated the protein and mRNA expression levels of
      Bax and p53 in SGC-7901 cells, but downregulated the protein and mRNA expressions
      of Bcl-2. CONCLUSIONS: SPPW formula inhibits the proliferation of SGC-7901 cells
      in vitro and induces the cell apoptosis. It plays an anticancer role by
      regulating the expressions of Bax, p53 and Bcl-2 in SGC-7901 cells.

PMID- 23001461
TI  - Inhibitory effects of Qushuanling Capsule () on thrombus formation and platelet
      aggregation in rats.
AB  - OBJECTIVE: To investigate the effects of Qushuanling Capsule ( QSLC) on thrombus
      formation and platelet aggregation in rats. METHODS: Arteriovenous bypass, venous
      thrombosis, and middle cerebral artery thrombosis models were used in rats to
      investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese
      herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin
      or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2))
      and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) in rat plasma and aortic
      walls, were determined to investigate the possible mechanisms of the anti
      thrombotic effects of QSLC. RESULTS: After oral administration with QSLC for 7
      days, arteriovenous bypass thrombosis was obviously suppressed compared with the
      model group, venous thrombosis was also obviously suppressed, rat behaviors were
      obviously improved, and brain infarct size as well as water content were also
      reduced. The platelet aggregation induced by ADP or thrombin was inhibited by
      QSLC, but the drug had no effect on AA-induced platelet aggregation and content
      of TXB(2) and 6-keto-PGF1alpha in plasma and the aortic wall. CONCLUSION: These
      results suggest that QSLC can be used in the prevention and treatment of
      thrombotic diseases, and that its mechanism of action may be related to
      inhibition of platelet aggregation.

PMID- 23001462
TI  - Effects of sodium copper chlorophyllin on mesenchymal stem cell function in
      aplastic anemia mice.
AB  - OBJECTIVE: To investigate the effects of sodium copper chlorophyllin (SCC) on the
      proliferation, differentiation and immunomodulatory function of mesenchymal stem
      cells (MSCs) from mice with aplastic anemia. METHODS: A mouse model of aplastic
      anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy
      Co60 gamma radiation, followed by transplantation of 2*10(6) lymph node cells
      from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice
      were randomly divided into six groups: the treated groups, which received 25, 50,
      or 100 mg/kg/day SCC, respectively; a positive control group treated with
      cyclosporine A (CsA); and an untreated model control group (model group); while,
      the non-irradiated mice as the normal control group. SCC or CsA were administered
      by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral
      blood cells were counted and colony-forming fibroblasts (CFU-F) in the bone
      marrow were assayed. The ability of MSCs to form calcium nodes after culture in
      osteoinductive medium was also observed. The immunosuppressive effect of MSCs on
      T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow
      cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia. RESULTS:
      Peripheral blood white cell and platelet counts were increased by medium and high
      SCC doses, compared with the untreated control. CFU-Fs were also increased
      compared with the untreated control, and the numbers of calcium nodes in MSCs in
      osteoinductive medium were elevated in response to SCC treatment. The percentage
      of Forkhead box protein 3 (FOXP3(+)) T cells was increased in T cell-MSC
      cocultures, and the cytokine transforming growth factor beta1 was up-regulated in
      SCC-treated groups. CONCLUSION: The results of this study suggest that SCC not
      only promotes the proliferation and differentiation of MSCs, but also improves
      their immunoregulatory capacity in mice with aplastic anemia.

PMID- 23001463
TI  - Effects of Baduanjin () exercise on knee osteoarthritis: a one-year study.
AB  - OBJECTIVES: Knee osteoarthritis (OA) is a major cause of pain and functional
      limitation. Short-term Baduanjin () exercise had been testified to be beneficial
      to the disease. This study conducted an initial assessment of the one-year
      Baduanjin exercise on knee OA. METHODS: The recruited patients practiced
      Baduanjin at the community recreational center. Sessions were held for 30 min
      five times a week for one year. Knee pain, stiffness, physical disability,
      general health, knee extensors and flexors strength, and aerobic ability were
      measured using the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC), the Medical Outcomes Study Short Form-36 (SF-36), the 6-Minute Walk Test
      (6-MWT), and the Isokinetic Strength of the Knee Extensors and Flexors (ISKEF).
      Body mass index (BMI) was also calculated before and after the study period for
      comparison. RESULTS: Twenty-eight patients signed the informed consent. Six
      patients withdrew from the trial. Twenty-two patients (29 knees) completed the
      one-year study. After one-year Baduanjin exercise, WOMAC pain (132.0+/-69.6 vs.
      56.2+/-67.6, P=0.000), stiffness (64.7+/-54.8 vs. 22.3+/-34.6, P=0.000), and
      physical function subscales (386.1+/-275.8 vs. 182.0+/-235.7, P=0.003); SF-36
      body pain (45.7+/-20.0 vs. 57.4+/-17.9, P=0.005), general health (50.5+/-20.0 vs.
      62.1+/-16.1, P=0.004), role emotional (64.4+/-26.1 vs. 73.5+/-21.3, P=0.047), and
      health transition (3.3+/-1.0 vs. 2.6+/-1.0, P=0.008); BMI (25.0+/-2.9 vs. 24.4+/
      2.9, P=0.032); 6-MWT (565.7+/-94.6 vs. 610.5+/-66.7, P=0.036); and ISKEF Peak
      Torque (the Knee Extensors: 60.5+/-25.5 vs. 76.8+/-31, P=0.000; the Knee Flexors:
      29.3+/-15.9 vs. 37.1+/-15.8, P=0.001) were significantly improved. No adverse
      effects resulted from the exercise. CONCLUSIONS: It suggested that the long-term
      Baduanjin could be a feasible and safe exercise option for knee OA.

PMID- 23001464
TI  - Tanshinone II A inhibits dendritic cell-mediated adaptive immunity: potential
      role in anti-atherosclerotic activity.
AB  - OBJECTIVE: Antigen-presenting cells such as monocytes and dendritic cells (DCs)
      stimulate T-cell proliferation and activation during adaptive immunity. This
      cellular interaction plays a role in the growth of atherosclerotic plaques.
      Tanshinone II A (TSN) had been shown to decrease the growth of atherosclerotic
      lesions. We therefore investigated the ability of TSN to inhibit human monocyte
      derived DCs and their T-cellstimulatory capacity. METHODS: DCs derived from human
      monocytes cultured with recombinant human interleukin (IL)-4 and recombinant
      human granulocyte-macrophage colony-stimulating factor were co-cultured with TSN
      and lipopolysaccharide for 48 h. Phosphate-buffered saline was used as a negative
      control. Activation markers and the capacity of DCs for endocytosis were measured
      by flow cytometry, and proinflammatory cytokines were measured by enzyme-linked
      immunosorbent assays. DCs were co-cultured with lymphocytes to measure T-cell
      proliferation and IL-2 secretion by mixed lymphocyte reactions. RESULTS: TSN dose
      dependently attenuated DC expression of costimulatory molecules (CD86), and
      decreased expression of major histocompatibility complex class II (human
      loukocyte antigen-DR) and adhesion molecules (CD54). Moreover, TSN reduced
      secretion of the proinflammatory cytokines IL-12 and IL-1 by human DCs, and
      restored the capacity for endocytosis. Finally, TSN-preincubated DCs showed a
      reduced capacity to stimulate T-cell proliferation and cytokine secretion.
      CONCLUSIONS: TSN inhibits DC maturation and decreases the expression of
      proinflammatory cytokines, while impairing their capacity to stimulate T-cell
      proliferation and cytokine secretion. These effects may contribute to the
      influence of TSN on the progression of atherosclerotic lesions.

PMID- 23001465
TI  - Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia
      caused by mutation in CYP24A1 gene.
AB  - We report on a male infant presenting at 4 months of age with failure to thrive,
      dehydration, hypotonia, lethargy, and vomiting. Laboratory and imaging tests
      revealed severe hypercalcemia (5.8 mmol/l), suppressed parathyroid hormone (0.41
      pmol/l), hypercalciuria (8.0 mmol/mmol creatinine), elevated 25-hydroxyvitamin D3
      (over 600 nmol/l), and nephrocalcinosis. These symptoms are characteristic of
      idiopathic infantile hypercalcemia (IIH, MIM 143880). Conservative therapy
      (parenteral rehydration, diuretics, corticosteroids, bisphosphonates, and vitamin
      D prophylaxis withdrawal) was not able to improve the symptoms and laboratory
      values, and acute hemodiafiltration was necessary to normalize hypercalcemia.
      Clinical symptoms resolved rapidly after normalization of serum calcium levels.
      Molecular genetic testing revealed a homozygous mutation (R396W) in the CYP24A1
      gene (MIM 126065) encoding 25-hydroxyvitamin D3 24-hydroxylase, which is the key
      enzyme responsible for 1,25-dihydroxyvitamin D3 degradation. The CYP24A1 gene
      mutation leads to the increased sensitivity of the patients to even prophylactic
      doses of vitamin D and to the development of severe symptomatic hypercalcemia in
      patients with IIH. CONCLUSION: Our patient is only the thirteenth patient with
      IIH caused by mutation in the CYP24A1 gene and the first one needing acute
      hemodiafiltration for severe symptomatic hypercalcemic crisis. In all patients
      with suspected IIH the DNA analysis for CYP24A1 gene mutations should be
      performed regardless of the type of vitamin D supplementation and serum levels of
      vitamin D.

PMID- 23001466
TI  - The use of sodium-chloride difference and chloride-sodium ratio in the evaluation
      of metabolic acidosis in critically ill patients.

PMID- 23001467
TI  - Does Behcet's disease associate with neuropathic pain syndrome and impaired well
      being?
AB  - Previously peripheral neuropathy signs have been reported in inflammatory chronic
      diseases but the presence of neuropathic pain syndrome (NPS) in Behcet's disease
      (BD) is unclear. The aim of this study was to investigate the association of BD
      with NPS and impaired quality of life and sleep quality. A total of 111 patients
      diagnosed as BD and 52 healthy controls were included. Pain severity was assessed
      by visual analogue scale (VAS) in rest and during activity. The NPS was diagnosed
      according to the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)
      index. The well-being and sleep disturbances of the groups were evaluated with
      Psychological General Well-Being (PGWB) Scale and Pittsburg Sleep Quality Index
      (PSQI). Although there were no one with NPS in healthy controls, the proportion
      of NPS in patients with BD was 19.8 % (p = 0.001). The VAS scores both in
      activity and at rest were higher in BD (p < 0.001). There was statistically
      significant decrease in total PGWB score in BD patients compared to healthy
      controls (p < 0.001). And significant increase in LANSS score was observed in
      patients with BD compared to healthy controls (p = 0.000). The total LANSS scores
      showed significant positive correlation with PSQI scores (r = 0.322) and negative
      correlation with total PGWB scores (r = -0.672) in patients with BD. We observed
      a positive correlation between LANSS and VAS (rest and activity) scores (r =
      0.44, r = 0.42 respectively). The NPS seems to be associated with BD which should
      be taken into consideration in patients with neuropathic signs. The quality of
      life (QoL) and quality of sleep of the patients with BD were found to be impaired
      and this may be due to the presence of NPS.

PMID- 23001468
TI  - Health-related quality of life in relation to walking habits and fitness: a
      population-based study of 75-year-olds.
AB  - PURPOSE: To assess health-related quality of life (HRQL) in relation to walking
      habits and fitness status in older persons. A second aim was to examine fitness
      status as a mediator in the relation between walking habits and HRQL. METHODS: A
      cross-sectional population-based sample of 75-year-olds from Gothenburg, Sweden,
      was examined (n = 698, response rate 61 %). Walking habits were assessed as
      weekly frequency and duration. HRQL was assessed with the Short Form-36 (SF-36)
      and fitness with maximal and self-selected gait speed, chair-stand, stair
      climbing capacity, grip strength and one-leg stance. RESULTS: The proportion of
      75-year-olds who attained recommended levels of moderate physical activity (>=
      150 min/week), described as walking, was 60 %. This was positively associated
      with most subscales of SF-36 and with all fitness tests except grip strength.
      Maximal gait speed was the fitness test with the highest correlations to all SF
      36 subscales. Fitness, described with maximal gait speed, was a partial mediator
      in most relations between walking habits and SF-36. After adjustment for
      confounders, associations between regular walking and SF-36 were no longer
      significant, except for Role Physical, General Health and Role Emotional in
      women. CONCLUSIONS: Attaining recommended levels of walking, as well as a high
      fitness status, is positively associated with several aspects of HRQL in older
      persons. Fitness, described with maximal gait speed, seems to have a partial role
      in the relation between walking habits and HRQL, suggesting that other mechanisms
      are also involved.

PMID- 23001469
TI  - Dynamics of a intraguild predation model with generalist or specialist predator.
AB  - Intraguild predation (IGP) is a combination of competition and predation which is
      the most basic system in food webs that contains three species where two species
      that are involved in a predator/prey relationship are also competing for a shared
      resource or prey. We formulate two intraguild predation (IGP: resource, IG prey
      and IG predator) models: one has generalist predator while the other one has
      specialist predator. Both models have Holling-Type I functional response between
      resource-IG prey and resource-IG predator; Holling-Type III functional response
      between IG prey and IG predator. We provide sufficient conditions of the
      persistence and extinction of all possible scenarios for these two models, which
      give us a complete picture on their global dynamics. In addition, we show that
      both IGP models can have multiple interior equilibria under certain parameters
      range. These analytical results indicate that IGP model with generalist predator
      has "top down" regulation by comparing to IGP model with specialist predator. Our
      analysis and numerical simulations suggest that: (1) Both IGP models can have
      multiple attractors with complicated dynamical patterns; (2) Only IGP model with
      specialist predator can have both boundary attractor and interior attractor,
      i.e., whether the system has the extinction of one species or the coexistence of
      three species depending on initial conditions; (3) IGP model with generalist
      predator is prone to have coexistence of three species. 

PMID- 23001470
TI  - Arsenic speciation and mobility in surface water at Lucky Shot Gold Mine, Alaska.
AB  - Historical mining in Alaska has created a legacy of approximately 6,830 abandoned
      mine sites which include adits, tailing piles and contaminated land that continue
      to impact surface and groundwater quality through run-off and leaching of
      potentially toxic metals, especially arsenic (As). One such site is the Lucky
      Shot Gold Mine in Hatcher Pass, south-central Alaska, which operated from 1920
      until 1942, mining gold-bearing quartz veins hosted in a Cretaceous tonalite
      intrusion. Arsenopyrite (FeAsS) and pyrite (FeS(2)) present in the quartz veins
      contribute to elevated As levels in water draining, abandoned mine adits. As
      future underground mining at Lucky Shot may further adversely impact water
      quality, baseline geochemical studies were undertaken to assess As mobility in
      the vicinity of the mine adits. Water samples were collected from streams, adits
      and boreholes around the mine and analysed for major and minor elements using
      inductively coupled plasma-mass spectrometry (ICP-MS) and for anions by ion
      chromatography (IC). Arsenic species separation was performed in the field to
      determine the ratio of inorganic As(III)/As(V) using anion-exchange
      chromatography, following established methods. It was determined that water
      draining the adits had elevated levels of As roughly seventy times the United
      States Environmental Protection Agency Drinking Water Standard of 10 MUg L(-1),
      although this was rapidly diluted downstream in Craigie Creek to <2 MUg L(-1).
      Adit and surface water pH was circum-neutral and displayed no characteristics of
      acid mine drainage. Despite being well oxygenated, As(III) is the dominant As
      species in adit water, accounting for close to 100 % of total As. The proportion
      of As(V) increases downstream of the adits, as some As(III) is oxidized, but the
      speciation enhances arsenic mobility at the site. The delta(18)O measurements
      indicate that the water in the system has a short residence time as it is very
      similar to meteoric water, supporting the observation that the predominance of
      As(III) in adit water results from the lack of thermodynamical equilibrium being
      attained and preferential absorbance of As(V).

PMID- 23001471
TI  - Flux-based risk management strategy of groundwater pollutions: the CMF approach.
AB  - A site- and receptor-specific risk management strategy for groundwater pollution
      based on the measurement of contaminant mass flux is proposed. The approach is
      useful and compatible with the demands formulated in the European Water Framework
      Directive, its Groundwater Daughter Directive and the regulations applicable in
      the EU member states. The proposed CMF method focuses on the following: (1)
      capture zones, (2) the location of control planes, (3) the definition of the
      maximum allowed contaminant mass discharge and (4) contaminant mass flux
      measurements. For every control plane, such a maximum allowed contaminant mass
      discharge is derived and is crucial for the receptor risk management strategy.
      The method is demonstrated for a large area of groundwater pollution present in
      the industrial area of Vilvoorde-Machelen located in Flanders, Belgium.

PMID- 23001472
TI  - Geochemical baselines of heavy metals in the sediments of two large freshwater
      lakes in China: implications for contamination character and history.
AB  - The aim of this study was to estimate the geochemical baseline concentrations of
      various heavy metals in the surface sediments of two large freshwater lakes in
      Taihu and Dianchi, China, and to assess the character and history of heavy metal
      contamination around the two lakes. Heavy metal concentrations in the sediments
      were obtained by field surveys and were supplemented with published data. The
      statistical methods of cumulative frequency and normalization were employed to
      obtain the baselines. The respective baseline concentrations for As, Sb, Hg, Co,
      Cr, Cu, Ni, Pb and Zn were 9.92, 1.67, 0.14, 22.62, 100.56, 31.63, 31.97, 33.05
      and 97.01 mg/kg, respectively, in Taihu, and 24.60, 4.29, 0.25, 36.78, 135.68,
      90.05, 50.76, 73.56 and 208.76 mg/kg, respectively, in Dianchi. The baseline
      concentrations of these heavy metals in Lake Taihu were equivalent to the pre
      industrial concentrations determined from lakes in Sweden and Europe. Conversely,
      those in Lake Dianchi were much higher than the pre-industrial values. Li, Fe,
      Sc, Ti, V and Al were found to be the suitable reference elements for
      normalization, and one of these elements could be used to predict the baseline
      concentrations of heavy metals except Hg. Most of the heavy metals had one
      inflexion, and only Cu and Pb in Taihu, Sb, Pb and Zn in Dianchi, were found to
      have two inflexions in the cumulative curves, suggesting remarkable anthropogenic
      inputs of Cu and Pb in Taihu, Sb, Pb and Zn in Dianchi, which are generally
      consistent with the respective industrial structure around Taihu and Dianchi.

PMID- 23001473
TI  - The effect of conventional wastewater treatment on the levels of antimicrobial
      resistant bacteria in effluent: a meta-analysis of current studies.
AB  - Antimicrobial agents in the environment are a cause for concern. Antimicrobial
      drug residues and their metabolites reach the aquatic and terrestrial environment
      primarily through wastewater treatment plants (WWTP). In addition to the
      potential direct negative health and environmental effects, there is potential
      for the development of antimicrobial-resistant bacteria. Residue levels below the
      minimum inhibitory concentration for a bacterial species can be important in
      selection of resistance. There is uncertainty associated with resistance
      formation during WWTP processing. A meta-analysis study was carried out to
      analyse the effect of WWTP processing on the levels of antimicrobial-resistant
      bacteria within bacterial populations. An analysis of publications relating to
      multiple antimicrobial-resistant (MAR) bacteria (n = 61), single antimicrobial
      resistant (SAR) E. coli (n = 81) and quinolone/fluoroquinolone-resistant (FR)
      bacteria (n = 19) was carried out. The odds-ratio (OR) of MAR (OR = 1.60, p <
      0.01), SAR (OR = 1.33, p < 0.01) and FR (OR = 1.19, p < 0.01) bacteria was
      determined. The results infer that WWTP processing results in an increase in the
      proportion of resistant bacteria in effluent, even though the overall bacterial
      population may have reduced (i.e. a reduction in total bacterial numbers but an
      increase in the percentage of resistant bacteria). The results support the need
      for further research into the development of antimicrobial-resistant strains and
      possible selective pressures operating in WWTPs.

PMID- 23001474
TI  - Clinical pharmacology considerations in biologics development.
AB  - Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins
      such as cytokines and growth hormones, have unique characteristics compared to
      small molecules. This paper starts from an overview of the pharmacokinetics (PK)
      of biologics from a mechanistic perspective, the determination of a starting dose
      for first-in-human (FIH) studies, and dosing regimen optimisation for phase
      II/III clinical trials. Subsequently, typical clinical pharmacology issues along
      the corresponding pathways for biologics development are summarised, including
      drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific
      populations. The relationships between the molecular structure of biologics,
      their pharmacokinetic and pharmacodynamic characteristics, and the corresponding
      clinical pharmacology strategies are summarised and depicted in a schematic
      diagram.

PMID- 23001476
TI  - Recent cases of invasive alien mites and ticks in Japan: why is a regulatory
      framework needed?
AB  - Japan's economy depends on the importation of natural resources, and as a result,
      Japan is subjected to a high risk of biological invasion. Although Japan has
      quarantine systems to protect ecosystems, agriculture, forestry, fisheries, and
      human health against alien species, economic globalization has resulted in an
      ever-increasing risk of invasion. Mite invasion is no exception. Alien species
      that impact natural ecosystems are regulated in Japan by the Invasive Alien
      Species Act. However, the law focuses only on visibly recognizable species, so
      that species too small to see, such as viruses, bacteria, fungi, and mites, are
      beyond the scope of this law. The Plant Protection Law has limited the
      introduction of alien pests, including mites, that are harmful to agricultural
      crops. Recently, the liberalization of global trade policies have increased
      pressure to loosen regulations on various pests, including spider mites.
      Infectious diseases and their causative species are quarantined under the Rabies
      Prevention Law, the Domestic Animal Infectious Diseases Control Law, and the
      Human Infectious Diseases Control Law, but these laws do not cover wildlife
      diseases. The most serious problem is that wild reptiles, which can be carriers
      of ticks and tick-borne diseases, can be freely introduced to Japan. These
      loopholes in Japan's regulatory system have resulted in mite and tick invasions,
      which affect not only wildlife communities and human society but also endemism
      and biological diversity of natural mite populations.

PMID- 23001475
TI  - Coumarin-based fluorescent probes for H2S detection.
AB  - Although hydrogen sulfide (H(2)S) has been known as a toxic gas with unpleasant
      rotten egg smell, the correlation between H(2)S and physiological processes has
      attracted scientists to develop brand new methods to monitor such a gaseous
      molecule in vitro and in vivo. Herein, we described a couple of coumarin-based
      fluorescent probes (1a and 1b) that can be activated by reduction of azide to
      amine in the presence of H(2)S. It should be emphasized that probe 1b
      demonstrated high selectivity and sensitivity for H(2)S over other relevant
      reactive sulfur species in vitro, as well as identified exogenous H(2)S in living
      cells.

PMID- 23001478
TI  - Differential expression of junctional adhesion molecules in different stages of
      systemic sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is characterized by early perivascular
      inflammation, microvascular endothelial cell (MVEC) activation/damage, and
      defective angiogenesis. Junctional adhesion molecules (JAMs) regulate leukocyte
      recruitment to sites of inflammation and ischemia-reperfusion injury, vascular
      permeability, and angiogenesis. This study was undertaken to investigate the
      possible role of JAMs in SSc pathogenesis. METHODS: JAM-A and JAM-C expression
      levels in skin biopsy samples from 25 SSc patients and 15 healthy subjects were
      investigated by immunohistochemistry and Western blotting. Subcellular
      localization of JAMs in cultured healthy dermal MVECs and SSc MVECs was assessed
      by confocal microscopy. Serum levels of soluble JAM-A (sJAM-A) and sJAM-C in 64
      SSc patients and 32 healthy subjects were examined by enzyme-linked immunosorbent
      assay. RESULTS: In control skin, constitutive JAM-A expression was observed in
      MVECs and fibroblasts. In early-stage SSc skin, JAM-A expression was strongly
      increased in MVECs, fibroblasts, and perivascular inflammatory cells. In late
      stage SSc, JAM-A expression was decreased compared with controls. JAM-C was
      weakly expressed in control and late-stage SSc skin, while it was strongly
      expressed in MVECs, fibroblasts, and inflammatory cells in early-stage SSc.
      Surface expression of JAM-A was higher in early-stage SSc MVECs and increased in
      healthy MVECs stimulated with early-stage SSc sera. JAM-C was cytoplasmic in
      resting healthy MVECs, while it was recruited to the cell surface upon challenge
      with early-stage SSc sera. Early-stage SSc MVECs exhibited constitutive surface
      JAM-C expression. In SSc, increased levels of sJAM-A and sJAM-C correlated with
      early disease and measures of vascular damage. CONCLUSION: Our findings indicate
      that JAMs may participate in MVEC activation, inflammatory processes, and
      impaired angiogenesis in different stages of SSc.

PMID- 23001479
TI  - Morphine induces hyperalgesia without involvement of MU-opioid receptor or
      morphine-3-glucuronide.
AB  - Opioid-induced hyperalgesia (OIH) is a paradoxical increase in pain perception
      that may manifest during opioid treatment. For morphine, the metabolite morphine
      3-glucuronide (M3G) is commonly believed to underlie this phenomenon. Here, in
      three separate studies, we empirically assess the role of M3G in morphine-induced
      hyperalgesia. In the first study, CD-1 mice injected with morphine (15 mg/kg
      subcutaneously) after pretreatment with the opioid receptor antagonist naltrexone
      (NTX) (15 mg/kg) showed tail withdrawal latency reductions indicative of
      hyperalgesia (2.5 +/- 0.1 s at t = 30 min, P < 0.001 versus baseline). In these
      mice, the morphine/M3G concentration ratios versus effect showed a negative
      correlation (r(p) = -0.65, P < 0.001), indicating that higher morphine relative
      to M3G concentrations are associated with increased OIH. In the second study,
      similar hyperalgesic responses were observed in mice lacking the multidrug
      resistance protein 3 (MRP3) transporter protein (Mrp3(-/-) mice) in the liver and
      their wild-type controls (FVB mice; latency reductions: 3.1 +/- 0.2 s at t = 30
      min, P < 0.001 versus within-strain baseline). In the final study, the
      pharmacokinetics of morphine and M3G were measured in Mrp3(-/-) and FVB mice.
      Mrp3(-/-) mice displayed a significantly reduced capacity to export M3G into the
      systemic circulation, with plasma M3G concentrations just 7% of those observed in
      FVB controls. The data confirm previous literature that morphine causes
      hyperalgesia in the absence of opioid receptor activation but also indicate that
      this hyperalgesia may occur without a significant contribution of hepatic M3G.
      The relevance of these data to humans has yet to be demonstrated.

PMID- 23001480
TI  - Rapid detection of filoviruses by real-time TaqMan polymerase chain reaction
      assays.
AB  - Ebola virus (EBOV) and Marburg virus (MARV) are causative agents of severe
      hemorrhagic fever with high mortality rates in humans and non-human primates and
      there is currently no licensed vaccine or therapeutics. To date, there is no
      specific laboratory diagnostic test in China, while there is a national need to
      provide differential diagnosis during outbreaks and for instituting acceptable
      quarantine procedures. In this study, the TaqMan RT-PCR assays targeting the
      nucleoprotein genes of the Zaire Ebolavirus (ZEBOV) and MARV were developed and
      their sensitivities and specificities were investigated. Our results indicated
      that the assays were able to make reliable diagnosis over a wide range of virus
      copies from 10(3) to 10(9), corresponding to the threshold of a standard RNA
      transcript. The results showed that there were about 10(10) RNA copies per
      milliliter of virus culture supernatant, equivalent to 10,000 RNA molecules per
      infectious virion, suggesting the presence of many non-infectious particles.
      These data indicated that the TaqMan RT-PCR assays developed in this study will
      be suitable for future surveillance and specific diagnosis of ZEBOV and MARV in
      China.

PMID- 23001481
TI  - Regulation of hepatitis C virus replication and gene expression by the MAPK-ERK
      pathway.
AB  - The mitogen activated protein kinases-extracellular signal regulated kinases
      (MAPK-ERK) pathway is involved in regulation of multiple cellular processes
      including the cell cycle. In the present study using a Huh7 cell line Con1 with
      an HCV replicon, we have shown that the MAPK-ERK pathway plays a significant role
      in the modulation of HCV replication and protein expression and might influence
      IFN-alpha signalling. Epithelial growth factor (EGF) was able to stimulate ERK
      activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126
      led to an elevated HCV RNA load and higher NS5A protein amounts in Con1 cells. It
      could be further demonstrated that the inhibition of the MAPK-ERK pathway
      facilitated the translation directed by the HCV internal ribosome entry site.
      Consistently, a U0126 treatment enhanced activity of the HCV reporter replicon in
      transient transfection assays. Thus, the MAPK-ERK pathway plays an important role
      in the regulation of HCV gene expression and replication. In addition, cyclin
      dependent kinases (CDKs) downstream of ERK may also be involved in the modulation
      of HCV replication since roscovitine, an inhibitor of CDKs had a similar effect
      to that of U0126. Modulation of the cell cycle progression by cell cycle
      inhibitor or RNAi resulted consistently in changes of HCV RNA levels. Further,
      the replication of HCV replicon in Con1 cells was inhibited by IFN-alpha. The
      inhibitory effect of IFN-alpha could be partly reversed by pre-incubation of Con
      1 cells with inhibitors of the MAPK-ERK pathway and CDKs. It could be shown that
      the MAPK-ERK inhibitors are able to partially modulate the expression of
      interferon-stimulated genes.

PMID- 23001482
TI  - Comparison of immune responses against FMD by a DNA vaccine encoding the
      FMDV/O/IRN/2007 VP1 gene and the conventional inactivated vaccine in an animal
      model.
AB  - Foot-and-mouth disease virus (FMDV) is highly contagious and responsible for huge
      outbreaks among cloven hoofed animals. The aim of the present study is to
      evaluate a plasmid DNA immunization system that expresses the FMDV/O/IRN/2007 VP1
      gene and compare it with the conventional inactivated vaccine in an animal model.
      The VP1 gene was sub-cloned into the unique Kpn I and BamH I cloning sites of the
      pcDNA3.1+ and pEGFP-N1 vectors to construct the VP(1) gene cassettes. The
      transfected BHKT7 cells with sub-cloned pEGFP-N1-VP1 vector expressed GFP-VP1
      fusion protein and displayed more green fluorescence spots than the transfected
      BHKT7 cells with pEGFP-N1 vector, which solely expressed the GFP protein. Six
      mice groups were respectively immunized by the sub-cloned pcDNA3.1(+)-VP1 gene
      cassette as the DNA vaccine, DNA vaccine and PCMV-SPORT-GMCSF vector (as
      molecular adjuvant) together, conventional vaccine, PBS (as negative control),
      pcDNA3.1(+) vector (as control group) and PCMV-SPORT vector that contained the
      GMCSF gene (as control group). Significant neutralizing antibody responses were
      induced in the mice which were immunized using plasmid vectors expressing the VP1
      and GMCSF genes together, the DNA vaccine alone and the conventional inactivated
      vaccine (P<0.05). Co-administration of DNA vaccine and GMCSF gene improved
      neutralizing antibody response in comparison with administration of the DNA
      vaccine alone, but this response was the most for the conventional vaccine group.
      However, induction of humeral immunity response in the conventional vaccine group
      was more protective than for the DNA vaccine, but T-cell proliferation and IFN
      gamma concentration were the most in DNA vaccine with the GMCSF gene. Therefore
      the group that was vaccinated by DNA vaccine with the GMCSF gene, showed
      protective neutralizing antibody response and the most Th1 cellular immunity.

PMID- 23001483
TI  - Gender-specific effect of physical training on AQP7 protein expression in human
      adipose tissue.
AB  - AQP7 is a glycerol channel in adipose tissue with a suggested role in controlling
      the accumulation of triglycerides and secondly development of obesity and type-2
      diabetes. In the present study, we aimed to test the hypotheses that (1) AQP7 is
      localized to the capillaries within human adipose tissue, (2) genetic
      predisposition to type-2 diabetes is associated with a low expression of AQP7 in
      abdominal subcutaneous adipose tissue (SAT) and (3) physical training increases
      AQP7 expression in SAT. The cellular localization of AQP7 in adipose tissue was
      investigated by immunohistochemistry. The relative expression of AQP7 protein in
      abdominal SAT was analysed before and after ending a 10-week exercise training
      programme in first-degree relatives to type-2 diabetic patients and control
      individuals. Non-obese first-degree relatives to type-2 diabetic patients (n =
      20) and control (n = 11) men and women participated in this study. By this, we
      find that AQP7 is localized to the capillary endothelial cells within adipose
      tissue. We were unable to evidence a link between a low AQP7 abundance in SAT and
      genetic predisposition type-2 diabetes. Instead we demonstrate that physical
      training influences the expression of AQP7 in SAT in a gender-specific manner.
      Thus, women responds by increasing the abundance of AQP7 by 2.2-fold (p = 0.03)
      whereas in men a reduced expression is observed (p = 0.00009), resulting in a
      more than twofold higher abundance of AQP7 in women as compared with men. In
      conclusion, the adipose tissue glycerol channel, AQP7, is regulated in response
      to physical training in a gender-dependent manner in SAT.

PMID- 23001484
TI  - Comments on "background stratified poisson regression analysis of cohort data" by
      Richardson and Langholz, Radiat Environ Biophys 51(1): 15-22.

PMID- 23001485
TI  - The point spread function of the human head and its implications for transcranial
      current stimulation.
AB  - Rational development of transcranial current stimulation (tCS) requires solving
      the 'forward problem': the computation of the electric field distribution in the
      head resulting from the application of scalp currents. Derivation of forward
      models has represented a major effort in brain stimulation research, with model
      complexity ranging from spherical shells to individualized head models based on
      magnetic resonance imagery. Despite such effort, an easily accessible benchmark
      head model is greatly needed when individualized modeling is either undesired (to
      observe general population trends as opposed to individual differences) or
      unfeasible. Here, we derive a closed-form linear system which relates the applied
      current to the induced electric potential. It is shown that in the spherical
      harmonic (Fourier) domain, a simple scalar multiplication relates the current
      density on the scalp to the electric potential in the brain. Equivalently, the
      current density in the head follows as the spherical convolution between the
      scalp current distribution and the point spread function of the head, which we
      derive. Thus, if one knows the spherical harmonic representation of the scalp
      current (i.e. the electrode locations and current intensity to be employed), one
      can easily compute the resulting electric field at any point inside the head.
      Conversely, one may also readily determine the scalp current distribution
      required to generate an arbitrary electric field in the brain (the 'backward
      problem' in tCS). We demonstrate the simplicity and utility of the model with a
      series of characteristic curves which sweep across a variety of stimulation
      parameters: electrode size, depth of stimulation, head size and anode-cathode
      separation. Finally, theoretically optimal montages for targeting an
      infinitesimal point in the brain are shown.

PMID- 23001486
TI  - Distal hyperintense vessels on FLAIR images predict large-artery stenosis in
      patients with transient ischemic attack.
AB  - INTRODUCTION: Distal hyperintense vessels (DHV) are frequently detected by fluid
      attenuated inversion recovery (FLAIR) imaging in patients with acute ischemic
      stroke. Despite its relevance to patient care outcomes, the presence of DHV has
      not been evaluated in patients with transient ischemic attack (TIA). METHODS: We
      performed a retrospective analysis of all TIA patients admitted to the study
      hospital from 2006 to 2010 who had undergone magnetic resonance imaging (MRI)
      within 24 h of symptom onset followed by further intracranial and extracranial
      vascular imaging. We then analyzed the relationship between DHV, large artery
      severe stenosis or occlusion (LASO), and clinical presentation. RESULTS: Forty
      three TIA patients were enrolled in this study. DHV signals on FLAIR images were
      positive in 14 (33 %) patients. Patients with DHV were significantly more likely
      to have severe stenosis or occlusion in intracranial (P = 0.01) and extracranial
      vessels (P = 0.04) than patients without DHV. DHV was associated independently
      with LASO (odds ratio = 6.1; 95 % CI, 1.2-31.5). CONCLUSION: Evaluation of DHV
      signals on FLAIR images may facilitate prediction of LASO in TIA patients and
      therefore enable prompt vascular assessment.

PMID- 23001487
TI  - Cavernous malformations associated with dural arteriovenous shunts in the central
      nervous system.
AB  - INTRODUCTION: Some cerebral cavernous malformations (CCMs) may be associated with
      vascular malformations that occur on the capillary-venous side of the cerebral
      circulation. The association between CCMs and dural arteriovenous shunts (DAVSs)
      is not well known. The purpose of this study is to investigate the relationship
      between CCMs and DAVSs. METHODS: We retrospectively analyzed 179 patients
      diagnosed as intracranial DAVSs and performed with digital subtraction
      angiography (DSA). The DSA images were investigated for the location, cortical
      venous reflux (CVR), multiplicity, and treatment method/result of DAVS. MR images
      were investigated for the location, number, and size of CCMs and correlated with
      the DSA images. RESULTS: Six of the 179 patients with DAVSs presented with
      coexistent CCMs (3.4 %; M/F = 3:3; mean age, 38 +/- 22 years). Five of the six
      DAVS patients with CCMs were associated with CVR (83 %). The total number of CCMs
      associated with DAVS was 20. Multiple CCMs (range, 2-7) were seen in four (66 %)
      of six patients. Eighteen (90 %) of the 20 CCMs were located on the ipsilateral
      hemisphere of the CVR (n = 10) or adjacent to the deep venous reflux (n = 8).
      Five de novo CCMs were detected in two patients. All de novo CCMs were located on
      the ipsilateral hemisphere of the DAVS with CVR or juxtapositioned to abnormally
      dilated deep vein. CONCLUSION: CCMs may develop in association to DAVSs. The
      relationship between CCMs and DAVSs suggests the venous pathogenic origin of CCMs
      and the role of venous hypertension in the de novo development of CCMs.

PMID- 23001488
TI  - Open air mineral treatment operations and ambient air quality: assessment and
      source apportionment.
AB  - We present a methodology for evaluating and quantifying the impact of inhalable
      mineral dust resuspension close to a potentially important industrial point
      source, in this case an open air plant producing sand, flux and kaolin in the
      Capuchinos district of Alcaniz (Teruel, NE Spain). PM(10) levels at Capuchinos
      were initially high (42 MUg m(-3) as the annual average with 91 exceedances of
      the EU daily limit value during 2007) but subsequently decreased (26 MUg m(-3)
      with 16 exceedances in 2010) due to a reduced demand for minerals from the
      ceramic industry and construction sector during the first stages of the economic
      crisis. Back trajectory and local wind pattern analyses revealed only limited
      contribution from exotic PM sources such as African dust intrusions whereas there
      was clearly a strong link with the mineral stockpiles of the local industry. This
      link was reinforced by chemical and mineral speciation and source apportionment
      analysis which showed a dominance of mineral matter (sum of CO(3)(2-), SiO(2),
      Al(2)O(3), Ca, Fe, K, Mg, P, and Ti: mostly aluminosilicates) which in 2007
      contributed 76% of the PM(10) mass (44 MUg m(-3) on average). The contribution
      from Secondary Inorganic Aerosols (SIA, sum of SO(4)(2-), NO(3)(-) and NH(4)(+))
      reached 8.4 MUg m(-3), accounting for 14% of the PM(10) mass, similar to the
      amount of calcareous road dust estimated to be present (8 MUg m(-3); 13%).
      Organic matter and elemental carbon contributed 5.3 MUg m(-3) (9%) whereas marine
      aerosol (Na + Cl) levels were minor with an average concentration of 0.4 MUg m(
      3) (1% of the PM(10) mass). Finally, chemical and mineralogical analysis of
      stockpile samples and comparison with filter samples confirmed the local industry
      to be the major source of ambient PM(10) in the area.

PMID- 23001489
TI  - Streptococcus agalactiae infective endocarditis with large vegetation in a
      patient with underlying protein S deficiency.
AB  - We present a case of a patient with underlying protein S deficiency who suffered
      from infective endocarditis with a large anterior mitral leaflet (AML) mass of
      approximately 4.5 cm in length. Intraoperative transesophageal echocardiography
      (TEE) revealed the mass at the AML base and a rupture of the posterior mitral
      leaflet chordae tendinae. The vegetation's large size may have been caused by one
      or more of three factors: location, underlying disease, and the microorganism
      causing infection. Patients with protein S deficiency are prone to thromboembolic
      events during cardiac surgery. Infective endocarditis caused by Streptococcus
      agalactiae usually has a poor prognosis, and, thus, early surgery is recommended.

PMID- 23001490
TI  - Up-regulated tumor necrosis factor-associated factor 6 level is correlated with
      apoptosis in the rat cerebral ischemia and reperfusion.
AB  - Tumor necrosis-associated factor 6 (TRAF6) performs critical roles in mediating
      apoptosis-associated inflammatory processes in multiple cell types, but its role
      in cerebral ischemia-reperfusion (I/R) injury is still unclear. In the present
      study, we established a middle cerebral artery occlusion (MCAO) reperfusion model
      in rat, and evaluated both the cerebral inflammatory damage and the cell
      apoptosis by TTC staining and TUNEL method, respectively. The expression of TRAF6
      and the neural cell apoptosis was examined during the I/R pathophysiological
      process. Cerebral ischemia injury induced significant neuronal cell apoptosis,
      but after the onset of reperfusion, cell apoptosis was gradually alleviated. In
      accord with the trend of I/R injury and cell apoptosis, up-regulated TRAF6 mRNA
      expression and caspase-3 cleavage level were observed in the ischemia stage and
      the early stage of reperfusion accordingly, which indicated that the activation
      of TRAF6 correlated positively with the cell apoptosis. Immunohistochemistry
      staining further showed that the TRAF6 was mainly localized in the neuronal
      cells. Thus, our study suggested that TRAF6 is involved in the inflammatory
      process induced by cerebral ischemia-reperfusion, and functions partially as a
      pro-inflammatory adaptor to mediate cell apoptosis. 

PMID- 23001491
TI  - Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from
      cervical and head and neck tumor cell lines.
AB  - PURPOSE: To explore cancer stem cell susceptibility to a host's cytotoxic T
      lymphocyte (CTL)-mediated immune response. METHODS: We compared the
      susceptibility of putative CSC generated from cancer cell lines to immunologic
      recognition and killing by alloantigen-specific CD8(+) CTL. CSC-enriched spheroid
      culture-derived cells (SDC) exhibited higher expression of ALDH, ICAM1 and of
      stem/progenitor cell markers on all 3 tumor cell lines investigated and lower MHC
      class I on the cervical cancer cell line as compared to their monolayer-derived
      cells (MDC). RESULTS: The expression of ICAM1 and MHCI was upregulated by IFN
      gamma treatment. CSC populations were less sensitive to MHC class I-restricted
      alloantigen-specific CD8(+) CTL lysis as compared to matched MDC. IFN-gamma
      pretreatment resulted in over-proportionally enhanced lysis of SDC. Finally, the
      subset of ALDH(high) expressing SDC presented more sensitivity toward CD8(+) CTL
      killing than the ALDH(low) SDC. CONCLUSIONS: Tumor therapy resistance has been
      attributed to cancer stem cells (CSC). We show in vitro susceptibility of CSC to
      CTL-mediated lysis. Immunotherapy targeting of ALDH(+) CSC may therefore be a
      promising approach. Our results and method may be helpful for the development and
      optimization of adjuvants, as here exemplified for INF-gamma, for CSC-targeted
      vaccines, independent of the availability of CSC-specific antigens.

PMID- 23001492
TI  - Health-related quality of life and supportive care in patients with rare long
      term neurological conditions.
AB  - PURPOSE: Rare long-term neurological conditions (rLTNCs) may have significant
      impact on patients' health-related quality of life (HRQL); however, evidence is
      sparse. We assessed HRQL and access to supportive care in patients with rLTNCs.
      METHODS: Survey of patients with rare rLTNCs (motor neurone disease, Huntington's
      disease, cerebellar ataxia, progressive supranuclear palsy, multiple system
      atrophy, Charcot-Marie-Tooth disease and postpolio syndrome) to assess current
      access to health and social care, and HRQL using the Euroqol EQ-5D. RESULTS: A
      total of 266 participants with rLTNCs completed the survey. The HRQL of patients
      is substantially reduced compared to the general population. Many patients
      reported pain, were anxious or depressed and experienced problems with mobility,
      self-care and usual activities (mean EQ-5D index scores ranged from 0.2 to 0.44).
      Although some patients have accessed rehabilitative services, results suggest
      care coordination could be improved. CONCLUSIONS: Rare long-term neurological
      conditions have a significant impact on HRQL. Many patients with rLTNCs do not
      seem to be accessing the level of health and social care services that could
      improve their HRQL.

PMID- 23001494
TI  - Cyclamen Trochopteranthum: Cytotoxic activity and possible adverse interactions
      including drugs and carcinogens.
AB  - OBJECTIVE: To examine the effect of water extracts of cyclamen tubers on the
      expression of main cytochrome P450 (CYP450s) including CYP1A1, CYP1A2 CYP2E1,
      CYP2B6, CYP2C9 and CYP3A4 that participate in the metabolism of both drugs and
      carcinogens and cytotoxic activity in human cancer cell lines, namely HepG2 and
      Caco-2. METHODS: Cyclamen trochopteranthum tubers were extracted with dH(2)O and
      then lyophilized under vacuum. Infrared spectral study was made for extracts by
      Fourier transform infrared spectroscopy (FT-IR). Cytotoxic activity of cyclamen
      was determined by crystal violet staining in HepG2 and Caco-2 cells. CYP
      expression was determined by reverse transcription polymerase chain reaction (RT
      PCR). RESULTS: Cyclamen water extract had moderate cytotoxic activity. It was
      found that lethal concentration (LC50) value of the cyclamen extract was 50 and
      125 MUg/mL in HepG2 and Caco-2 cell lines, respectively. Moreover, it caused
      induction and suppression of CYP450s mRNA levels in HepG2 and Caco-2 cells.
      CONCLUSION: Cyclamen may have a potential not only inhibition and/or induction of
      the metabolism of certain co-administered drugs but also development of toxicity,
      mutagenesis and malignant transformation due to induction or suppression of the
      CYP450s dependent drug metabolizing enzymes.

PMID- 23001493
TI  - Hypotriglyceridemic effects of apple polyphenols extract via up-regulation of
      lipoprotein lipase in triton WR-1339-induced mice.
AB  - OBJECTIVE: To investigate the anti-hyperlipidemic effects of apple polyphenols
      extract (APE) in Triton WR-1339-induced endogenous hyperlipidemic model. METHODS:
      Firstly, APE was isolated and purified from the pomace of Red Fuji Apple and
      contents of individual polyphenols in APE were determined using high-performance
      liquid chromatography-mass spectrometry (HPLC-MS). Secondly, forty male National
      Institude of Health (NIH) mice were randomly divided into 5 groups with 8 animals
      in each group. The Fenofibrate Capsules (FC) group and APE groups received oral
      administration of respective drugs for 7 consecutive days. All mice except those
      in the normal group were intravenously injected through tail vein with Triton WR
      1339 on the 6th day. Serum and livers from all the mice were obtained 18 h after
      the injection. The changes in serum total cholesterol (TC), triglyceride (TG),
      lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were measured by
      respective kits. Finally, expression of hepatic peroxisome proliferator-activated
      receptor alpha (PPARalpha) mRNA was measured by real-time reverse transcription
      polymerase chain reaction (RT-PCR) method. RESULTS SERUM TC AND TG LEVELS
      SIGNIFICANTLY INCREASED IN TRITON WR-1339-INDUCED MODEL GROUP COMPARED WITH THE
      NORMAL GROUP (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE
      DEPENDENTLY REDUCED THE SERUM LEVEL OF TG IN HYPERLIPIDEMIC MICE (P<0.01). SERUM
      LPL AND HTGL ACTIVITIES SIGNIFICANTLY DECREASED IN TRITON WR-1339-INDUCED MODEL
      GROUP COMPARED WITH THE NORMAL GROUP (P<0.05). ORAL ADMINISTRATION OF APE [200
      AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY ELEVATED THE SERUM ACTIVITY OF LPL IN
      HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01). FURTHERMORE, COMPARED WITH THE NORMAL
      GROUP, HEPATIC MRNA LEVEL OF PPARalpha IN THE MODEL GROUP SIGNIFICANTLY DECREASED
      (P<0.01). ORAL ADMINISTRATION OF APE [200 AND 400 MG/(KG DAY)] DOSE-DEPENDENTLY
      ELEVATED THE EXPRESSION OF PPARalpha IN HYPERLIPIDEMIC MICE (P<0.05 OR P<0.01):
      CONCLUSION: APE could reduce TG level via up-regulation of LPL activity, which
      provides new evidence to elucidate the anti-hyperlipidemic effects of APE.

PMID- 23001495
TI  - Unbiased estimates of long-term net survival of solid cancers in France.
AB  - In cancer studies, net survival (observed if cancer was the only cause of death)
      is a useful indicator but survival estimation at 5 years is insufficient for
      planning healthcare needs. We estimated the net survivals at 5 and 10 years in a
      cohort of 387,961 patients who had solid tumors between 1989 and 2004 and were
      followed-up until January 1, 2008. The cases were actively followed-up. Net
      survival was estimated with the unbiased Pohar-Perme method. The standardized net
      survival used the international cancer survival standard weights. In men, the
      standardized net survivals ranged from 92% at 5 years and 89% at 10 years
      (testis) to 6% at 5 years and 5% at 10 years (pancreas). In women, it ranged from
      91% at 5 years and 88% at 10 years (thyroid) to 10% at 5 years and 7% at 10 years
      (pancreas). The most frequent cancers had the highest net survivals: 84% at 5
      years and 71% at 10 years for prostate and 84% at 5 years and 74% at 10 years for
      breast cancer. Advanced age was associated with poorer prognosis. In most
      cancers, the net survivals at 5 and 10 years increased over periods of diagnosis.
      Net cancer survival is unaffected by mortalities due to other causes. It is the
      only indicator suitable for comparisons between countries or periods of diagnosis
      within a given country. The 10-year net survival confirmed the persistent
      unfavorable role of age in prognosis and the general improvement of cancer
      management over the last decade.

PMID- 23001497
TI  - Relationship commitment, perceived equity, and sexual enjoyment among young
      adults in the United States.
AB  - Very little is known about how enjoyment of sexual behavior is linked to the
      relationship context of the behavior among young adults in the United States. To
      examine this association, multivariate logistic and ordered logistic regression
      analyses were conducted using data from Wave III of the National Longitudinal
      Study of Adolescent Health, collected when the participants were 18 to 26 years
      old (N = 2,970). Analyses explored the associations between four measures of
      sexual enjoyment and three measures of relationship context. Perceived equity was
      associated with sexual enjoyment, but the pattern of associations differed by
      gender. Perceiving oneself to be underbenefited was associated with less
      enjoyment for all four measures of sexual enjoyment among women, but for only one
      measure among men. Perceiving oneself to be overbenefited was associated with
      less enjoyment for three of the sexual enjoyment measures among men, but for only
      two among women. Most of these associations were no longer significant when
      subjective relationship commitment was added to the models. Among both young
      adult men and women, subjective relationship commitment was associated with all
      four measures of sexual enjoyment. In contrast, formal relationship status was
      not consistently associated with any of the sexual enjoyment measures. Young
      adults perceiving that they are in more-committed relationships enjoy their
      partnered sexual acts more, on average, than those in less-committed
      relationships. Anticipation of higher sexual enjoyment could be used by public
      health campaigns to motivate young adults to engage in fewer, more-committed
      sexual partnerships.

PMID- 23001498
TI  - Satisfaction with open sexual agreements in Australian gay men's relationships:
      the role of perceived discrepancies in benefit.
AB  - This study investigated whether satisfaction with open sexual agreements in gay
      men's relationships was associated with perceptions of discrepancies in the
      benefit experienced from those agreements. Three types of perceived discrepancy
      between the self and the relationship partner were examined: frequency of casual
      sex, attractiveness of casual partners, and "overall" benefit. Results from a
      survey conducted in 2010 of 685 Australian gay men in relationships with open
      agreements showed that men perceiving discrepancies in benefit, particularly
      those representing "under-benefit", were less satisfied with their agreement than
      were men perceiving equal benefit. These results supported hypotheses derived
      from equity theory and provide insight into factors associated with gay men's
      satisfaction with open agreements. These findings also have important practical
      implications. Professionals counselling gay men or couples experiencing low
      satisfaction with open agreements may consider raising issues of unequal benefit
      and work with their clients towards achieving equality. 

PMID- 23001499
TI  - Acetabular distraction: an alternative for severe defects with chronic pelvic
      discontinuity?
AB  - BACKGROUND: Stabilization of a pelvic discontinuity with a posterior column plate
      with or without an associated acetabular cage sometimes results in persistent
      micromotion across the discontinuity with late fatigue failure and component
      loosening. Acetabular distraction offers an alternative technique for
      reconstruction in cases of severe bone loss with an associated pelvic
      discontinuity. QUESTIONS/PURPOSES: We describe the acetabular distraction
      technique with porous tantalum components and evaluate its survival, function,
      and complication rate in patients undergoing revision for chronic pelvic
      discontinuity. METHODS: Between 2002 and 2006, we treated 28 patients with a
      chronic pelvic discontinuity with acetabular reconstruction using acetabular
      distraction. A porous tantalum elliptical acetabular component was used alone or
      with an associated modular porous tantalum augment in all patients. Three
      patients died and five were lost to followup before 2 years. The remaining 20
      patients were followed semiannually for a minimum of 2 years (average, 4.5 years;
      range, 2-7 years) with clinical (Merle d'Aubigne-Postel score) and radiographic
      (loosening, migration, failure) evaluation. RESULTS: One of the 20 patients
      required rerevision for aseptic loosening. Fifteen patients remained
      radiographically stable at last followup. Four patients had early migration of
      their acetabular component but thereafter remained clinically asymptomatic and
      radiographically stable. At latest followup, the average improvement in the
      patients not requiring rerevision using the modified Merle d'Aubigne-Postel score
      was 6.6 (range, 3.3-9.6). There were no postoperative dislocations; however, one
      patient had an infection, one a vascular injury, and one a bowel injury.
      CONCLUSIONS: Acetabular distraction with porous tantalum components provides
      predictable pain relief and durability at 2- to 7-year followup when
      reconstructing severe acetabular defects with an associated pelvic discontinuity.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 23001500
TI  - Surgical technique: Tibia cortical strut autograft interposition arthrodesis
      after distal radius resection.
AB  - BACKGROUND: Distal radius reconstruction after en bloc tumor resection remains a
      surgical challenge. Although several surgical techniques, either reconstructing
      the wrist or achieving a stable arthrodesis, have been described, it is unclear
      to what degree these restore function. DESCRIPTION OF TECHNIQUE: We describe an
      updated technique making use of a tibia cortical strut autograft (TCSA) to
      perform a functional arthrodesis from the remaining radius to the first carpal
      row. This, in theory, could lead to less donor site morbidity while resulting in
      a stable but functional and pain-free arthrodesis of the wrist. METHODS: Between
      1987 and 2010 we reconstructed the wrists of 17 patients using a TCSA arthrodesis
      (six primary and three revisions), seven with an osteoarticular allograft, three
      using an ulnar translocation, and one with a fibula autograft. Median age at
      diagnosis was 24 years (range, 9-58 years) and minimum followup was 2.7 years
      (median, 13.8 years; range, 2.7-24.5 years). Patients were evaluated using
      radiographs and clinical examination. We used Musculoskeletal Tumor Society
      (MSTS), Disabilities of the Arm, Shoulder, and Hand (DASH), and SF-36
      questionnaires to assess function and quality of life. RESULTS: All TCSA
      reconstructions fused; one patient had a second surgery to expedite union with
      the carpal row. After osteoarticular allograft, five patients were revised (three
      to a TCSA) for nonunion, fracture, or joint collapse. ROM and grip strength were
      comparable in both AO and TCSA, all above 60% of the contralateral side. Median
      MSTS and DASH scores were 73% and 6, respectively, and did not differ between the
      groups. The SF-36 scores showed less pain after TCSA; otherwise, all patients
      presented with comparable function. CONCLUSIONS: TCSA wrist arthrodesis resulted
      in a functional and painless wrist reconstruction with a relatively low
      complication and donor site morbidity rate and comparable functional results as
      other techniques. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 23001501
TI  - How does bone quality differ between healthy-weight and overweight adolescents
      and young adults?
AB  - BACKGROUND: Overweight youth have greater bone mass than their healthy-weight
      peers but sustain more fractures. However, it is unclear whether and how excess
      body fat influences bone quality in youth. QUESTIONS/PURPOSES: We determined
      whether overweight status correlated with three-dimensional aspects of bone
      quality influencing bone strength in adolescent and young adult females and
      males. METHODS: We categorized males (n=103; mean age, 17 years) and females
      (n=85; mean age, 18 years) into healthy-weight and overweight groups. We measured
      lean mass (LM) and fat mass (FM) with dual-energy x-ray absorptiometry (DXA). We
      used high-resolution peripheral quantitative CT to assess the distal radius (7%
      site) and distal tibia (8% site). Bone quality measures included total bone
      mineral density (Tt.BMD), total area (Tt.Ar), trabecular bone volume fraction
      (BV/TV), trabecular number (Tb.N), separation (Tb.Sp), and thickness (Tb.Th). We
      used multiple regression to compare bone quality between healthy-weight and
      overweight adolescents adjusting for age, ethnicity, limb length, LM, and FM.
      RESULTS: Overweight males had higher (10%-21%) Tt.BMD, BV/TV, and Tb.N and lower
      Tb.Sp at the tibia and lower Tt.Ar at the radius than healthy-weight males. No
      differences were observed between overweight and healthy-weight females. LM
      attenuated the differences in bone quality between groups in males while FM
      negatively predicted Tt.BMD, BV/TV, Tb.N, and Tb.Th. CONCLUSIONS: Our data
      suggest overweight males have enhanced bone quality compared with healthy-weight
      males; however, when group differences are interpreted in the context of the
      mechanostat theory, it appears bone quality of overweight adolescents adapts to
      LM and not to greater FM.

PMID- 23001502
TI  - Pelvic tilt is minimally changed by total hip arthroplasty.
AB  - BACKGROUND: While surgical navigation offers the opportunity to accurately place
      an acetabular component, questions remain as to the best goal for acetabular
      component positioning in individual patients. Overall functional orientation of
      the pelvis after surgery is one of the most important variables for the surgeon
      to consider when determining the proper goal for acetabular component
      orientation. QUESTIONS/PURPOSES: We measured the variation in pelvic tilt in 30
      patients before THA and the effect of THA on pelvic tilt in the same patients
      more than a year after THA. METHODS: Each patient had a CT study for CT-based
      surgical navigation and standing and supine radiographs before and after surgery.
      Pelvic tilt was calculated for each of the radiographs using a novel and
      validated two-dimensional/three-dimensional matching technique. RESULTS: Mean
      supine pelvic tilt changed less than 2 degrees , from 4.4 degrees  +/- 6.4
      degrees  (range, -7.7 degrees  to 20.8 degrees ) before THA to 6.3 degrees  +/-
      6.6 degrees  (range, -5.7 degrees  to 19.6 degrees ) after THA. Mean standing
      pelvic tilt changed less than 1 degrees , from 1.5 degrees  +/- 7.2 degrees 
      (range, -13.1 degrees  to 12.8 degrees ) before THA to 2.0 degrees  +/- 8.3
      degrees  (range, -12.3 degrees  to 16.8 degrees ) after THA. Preoperative pelvic
      tilt correlated with postoperative tilt in both the supine (r(2) = 0.75) and
      standing (r(2) = 0.87) positions. CONCLUSIONS: In this population, pelvic tilt
      had a small and predictable change after surgery. However, intersubject
      variability of pelvic tilt was high, suggesting preoperative pelvic tilt should
      be considered when determining desired acetabular component positioning on a
      patient-specific basis.

PMID- 23001503
TI  - Bacteria adhere less to barbed monofilament than braided sutures in a
      contaminated wound model.
AB  - BACKGROUND: Previous studies have found fewer clinical infections in wounds
      closed with monofilament suture compared with braided suture. Recently, barbed
      monofilament sutures have shown improved strength and increased timesavings over
      interrupted braided sutures. However, the adherence of bacteria to barbed
      monofilament sutures and other commonly used suture materials is unclear.
      QUESTIONS/PURPOSES: We therefore determined: (1) the adherence of bacteria to
      five suture types including a barbed monofilament suture; (2) the ability to
      culture bacteria after gentle washing of each suture type; and (3) the pattern of
      bacterial adherence. METHODS: We created an experimental contaminated wound model
      using planktonic methicillin-resistant Staphylococcus aureus (MRSA). Five types
      of commonly used suture material were used: VicrylTM, VicrylTM Plus, PDSTM, PDSTM
      Plus, and QuillTM. To determine adherence, we determined the number of bacteria
      removed from the suture by sequential washes. Sutures were plated to determine
      bacterial growth. Sutures were examined under confocal microscopy to determine
      adherence patterns. RESULTS: The barbed monofilament suture showed the least
      bacterial adherence of any suture material tested. Inoculated monofilament and
      barbed monofilament sutures placed on agar plates had less bacterial growth than
      braided suture, whereas antibacterial monofilament and braided sutures showed no
      growth. Confocal microscopy showed more adherence to braided suture than to the
      barbed monofilament or monofilament sutures. CONCLUSIONS: Barbed monofilament
      suture showed similar bacterial adherence properties to standard monofilament
      suture. CLINICAL RELEVANCE: Our findings suggest barbed monofilament suture can
      be substituted for monofilament suture, at the surgeon's discretion, without fear
      of increased risk of infection.

PMID- 23001504
TI  - Can the alpha angle assessment of cam impingement predict acetabular cartilage
      delamination?
AB  - BACKGROUND: Substantial acetabular cartilage damage is commonly present in
      patients suffering from femoral acetabular impingement (FAI). A better
      understanding of which patient is at risk of developing substantial cartilage
      damage is critical for establishing appropriate treatment guidelines.
      QUESTIONS/PURPOSES: We asked: (1) Does the cam deformity severity in FAI as
      assessed by alpha angle predict acetabular cartilage delamination? And (2) what
      are the clinical and radiographic findings in patients with acetabular cartilage
      delamination? METHODS: One hundred sixty-seven patients (129 males, 38 females)
      with a mean age of 38 years (range, 17-59 years) underwent joint preservation
      surgery for cam-type FAI. All data were collected prospectively. We assessed
      center-edge angle and Tonnis grade on AP radiographs and alpha angle on
      specialized lateral radiographs. Acetabular cartilage damage was assessed
      intraoperatively using the classification of Beck et al., with Type 3 and greater
      qualifying as delamination. RESULTS: For all hips, mean alpha angle was 65.5
      degrees  (range, 41 degrees -90 degrees ), and mean center-edge angle was 33.3
      degrees  (range, 21 degrees -52.5 degrees ). Patients with an alpha angle of 65
      degrees  or greater had an odds ratio (OR) of 4.00 (95% CI, 1.26-12.71) of having
      Type 3 or greater damage. Increased age (OR, 1.04; 95% CI, 1.01-1.07) and male
      sex (OR, 2.24; 95% CI, 1.09-4.62) were associated with Type 3 or greater damage,
      while this was the opposite for acetabular coverage as assessed by center-edge
      angle (OR, 0.94; 95% CI, 0.89-0.99). CONCLUSIONS: Patients with cam-type FAI and
      an alpha angle of 65 degrees  or more are at increased risk of substantial
      cartilage damage while increasing acetabular coverage appears to have a
      protective effect. LEVEL OF EVIDENCE: Level III, prognostic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 23001505
TI  - Variables influencing pregnancy termination following prenatal diagnosis of fetal
      chromosome abnormalities.
AB  - The objective of this study was to identify variables that may influence the
      decision to terminate or continue a pregnancy affected by a chromosome
      abnormality. We performed a retrospective cohort analysis of 286 pregnancies
      diagnosed with a chromosome abnormality following genetic counseling and prenatal
      diagnosis. Data obtained included procedure type, chromosome results, ethnicity,
      maternal age, use of fertility treatments, and uptake of genetic counseling after
      results, among other factors. Wilcoxon rank sum test, Fisher's exact test, and
      univariate and multivariate logistic regression models were used for data
      analysis. The overall termination rate in this study was 82.9 %. A lower
      likelihood to terminate was found in pregnancies with a diagnosis of a sex
      chromosome abnormality (OR 0.05, p < .0001), Filipina race (OR 0.10, p = .03),
      and uptake of second genetic counseling session (OR 0.05, p < .0001). Prior
      history of termination was associated with increased likelihood to terminate (OR
      8.6, p = .02). Factors revealing no statistically significant association with
      termination included maternal age, gestational age, clinic site, fetal gender,
      ultrasound anomalies, reason for referral and who informed the patient. Our data
      affirm the complexity of the decision making process and reinforce that providers
      should refrain from making assumptions regarding a patient's likelihood to
      terminate based on factors such as maternal age, gestational age, type of
      procedure, or ultrasound.

PMID- 23001506
TI  - Interferon-inducible guanylate binding protein (GBP2) is associated with better
      prognosis in breast cancer and indicates an efficient T cell response.
AB  - BACKGROUND: Recently, interferon-inducible guanylate binding protein (GBP2) has
      been discussed as a possible control factor in tumor development, which is
      controlled by p53, and inhibits NF-Kappa B and Rac protein as well as expression
      of matrix metalloproteinase 9. However, the potential role that GBP2 plays in
      tumor development and prognosis has not yet been studied. METHODS: We analyzed
      whether GBP2 mRNA levels are associated with metastasis-free interval in 766
      patients with node negative breast carcinomas who did not receive systemic
      chemotherapy. Furthermore, response to anthracycline-based chemotherapy was
      studied in 768 breast cancer patients. RESULTS: High expression of GBP2 in breast
      carcinomas was associated with better prognosis in the univariate (P < 0.001,
      hazard ratio 0.763, 95 % CI 0.650-0.896) as well as in the multivariate Cox
      analysis (P = 0.008, hazard ratio 0.731, 95 % CI 0.580-0.920) adjusted to the
      established clinical factors age, pT stage, grading, hormone and ERBB2 receptor
      status. The association was particularly strong in subgroups with high
      proliferation and positive estrogen receptor status but did not reach
      significance in carcinomas with low expression of proliferation associated genes.
      Besides its prognostic capacity, GBP2 also predicted pathologically complete
      response to anthracycline-based chemotherapy (P = 0.0037, odds ratio 1.39, 95 %
      CI 1.11-1.74). Interestingly, GBP2 correlated with a recently established T cell
      signature, indicating tumor infiltration with T cells (R = 0.607, P < 0.001).
      CONCLUSION: GBP2 is associated with better prognosis in fast proliferating tumors
      and probably represents a marker of an efficient T cell response.

PMID- 23001507
TI  - Evaluation of the protective efficacy of the anticoccidial vaccine Coccivac-B in
      broilers, when challenged with Egyptian field isolates of E. tenella.
AB  - The present study was performed to explore the efficacy of the commercial
      anticoccidial vaccine (Coccivac B(r)) in broiler chickens using five field
      strains of Eimeria tenella that were isolated from five provinces in Egypt. This
      study also analyzed the ITS-1-rDNA sequence of these five strains and its
      corresponding sequence in the vaccine. In a floor pen experiment, 216 one-day-old
      commercial broiler chicks were classified into vaccinated and non-vaccinated
      groups. Each main group was classified into six subgroups. The chicks were
      challenged on the 28th day of age with 10(4) sporulated oocysts of one of the
      five field strains of E. tenella. Our results indicated that Coccivac B(r)
      produced variable degrees of protection in the birds infected with the five
      different strains of E. tenella. Aligning the ITS-1 sequences from the five
      strains with the ITS-1 sequence of E. tenella from the vaccine revealed 96 %
      sequence similarity with the Kafer El-Sheikh strain, 94 % with the Gharbia
      strain, 90 % with the Alexandria strain, and 78 % with the Matrouh and Behera
      strains. While interesting, these similarity values were not useful for
      predicting the protection conferred by the vaccine against the five field
      isolates. However, based on the data reported here, we can conclude that Coccivac
      B(r) produced variable degrees of protection in the birds infected with the five
      different strains of E. tenella.

PMID- 23001508
TI  - Field efficacy of praziquantel oral paste against naturally acquired equine
      cestodes in Ethiopia.
AB  - The efficacy of an oral formulation of praziquantel (Equitape, Horse paste, Fort
      Dodge) in the reduction of cestode egg counts and serum antibody level against
      Anoplocephala perfoliata was assessed in 44 donkeys under field conditions. The
      donkeys were confirmed both by faecal examination and serum antibody assessed by
      an enzyme-linked immunosorbent assay to have natural infection with tapeworms.
      The donkeys were randomly allocated into treatment (n = 22) and control (n = 22)
      groups. The treatment group was treated with both praziquantel and ivermectin
      (Ivomec, Merial) at a dose rate of 1 mg/kg and 200 MUg/kg, respectively while the
      control group was treated only with ivermectin. Faecal samples were collected
      before treatment (day-0) and 2, 6, 8, 12, and 16 weeks post-treatment while blood
      samples were collected before treatment and 8 and 16 weeks after treatment and
      analysed. The results of the study demonstrated that praziquantel paste was
      highly effective in reducing cestode eggs in donkeys and had an efficacy of more
      than 99 % until week 16 (day 112). No cestode egg reappearance by 16 weeks post
      treatment in any animal in the treatment group was observed while donkeys in the
      control group continued shedding cestode eggs. The immunological assay also
      showed a significant reduction in serum antibody level against A. perfoliata in
      treated donkeys compared to the control group (p = 0.0001). This marked decrease
      in serum antibody level indicates reduced risk of cestode-associated colic and
      other gastrointestinal disorders and clinical diseases. No adverse reactions or
      clinical effects were encountered in any animal within either group throughout
      the trial period.

PMID- 23001509
TI  - Finding unrecognized information in overactive bladder clinical trial data: a new
      approach to understanding placebo and treatment effects.
AB  - AIMS: To identify combinations of variables among overactive bladder (OAB)
      clinical trial subjects that allow prediction of those who are more--or less-
      likely to respond strongly to placebo, or to medication. METHODS: Data from two
      Phase IIIb clinical trials of solifenacin in OAB were combined. Predictive models
      for placebo and treatment responses were constructed using baseline variables
      including individual items from the OAB questionnaire. These models were reduced
      to an essential subset of predictor variables. Two outcome measures are reported:
      urgency and incontinence. RESULTS: In placebo subjects, 14 selected variables
      permitted distinction between those who responded with significant reductions in
      urgency and those who did not. A subset of nine variables in treated subjects
      permitted distinction between those more--or less--likely to respond to
      medication. Data for urgency were combined from both placebo and actively treated
      subjects to identify those who had one of the previously identified clusters of
      variables. It was possible to predict, among all subjects, who would be likely to
      experience a strong placebo or active treatment response and who would not. This
      process was also applied to incontinence data. CONCLUSIONS: We have developed a
      new process to help understand placebo and treatment responses and their
      relationships to baseline conditions. The effectiveness of these methods was
      indicated using data from two solifenacin clinical trials and would benefit from
      future validation using other data sets. Methods used here are suitable for
      predicting the placebo effect in other clinical trials.

PMID- 23001511
TI  - Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7
      dimethoxycoumarin and valproic acid.
AB  - Malignant melanoma (melanoma malignum) is one of the most dangerous types of
      tumor. It is very difficult to cure. In recent years, a lot of attention has been
      given to chemoprevention. This method uses natural and synthetic compounds to
      interfere with and inhibit the process of carcinogenesis. In this study, a new
      treatment strategy was proposed consisting of a combination of 5,7
      dimethoxycoumarin (DMC), an activator of melanogenesis, and valproic acid (VPA),
      a well-known drug that is one of the histone deacetylase inhibitors (HDACis). In
      conjunction with 1 mM VPA, all of the tested concentrations of DMC (10-150 MUM)
      significantly decreased the proliferation of A-375 cells. VPA and DMC also
      induced the synthesis of melanin and the formation of dendrite and star-shaped
      cells. Tyrosinase gene expression and tyrosinase activity significantly increased
      in response to VPA treatment. Pyrolysis with gas chromatography and mass
      spectrometry (Py-GC/MS) was used to investigate the structure of the isolated
      melanin. This showed that the quantitative and qualitative components of melanin
      degradation products are dependent on the type of applied melanogenesis inductor.
      Products derived from eumelanin were detected in the pyrolytic profile of melanin
      isolated from A-375 cells stimulated with DMC. Thermal degradation of melanin
      isolated from melanoma cells after exposure to VPA or a mixture of VPA and DMC
      revealed the additional presence of products derived from pheomelanin.

PMID- 23001510
TI  - Bloodstream infections caused by IMP-8-producing Enterobacteriaceae isolates: the
      need for clinical laboratory detection of metallo-beta-lactamases?
AB  - A retrospective study was conducted at a Taiwanese medical center to characterize
      bloodstream infections caused by IMP-8 metallo-beta-lactamase (MBL)-producing
      Enterobacteriaceae isolates and to assess the need for laboratory detection of
      IMP producers. We analyzed 37 patients infected with IMP-8 producers (two
      Escherichia coli, nine Klebsiella pneumoniae, 25 Enterobacter cloacae, and one
      Citrobacter freundii) and 107 patients infected with non-IMP-8 producers (eight
      E. coli, 26 K. pneumoniae, 70 E. cloacae, and three C. freundii) that were
      interpreted as carbapenem-nonsusceptible based on the updated Clinical and
      Laboratory Standards Institute (CLSI) 2010 guidelines. Only 18 (48.6 %) of the
      IMP-8 producers were regarded as potential carbapenemase producers based on the
      CLSI 2012 guidelines. The production of extended-spectrum beta-lactamases (ESBLs)
      was more common in the MBL group (73.0 %) than in the non-MBL group (41.1 %).
      There were no significant differences in carbapenem susceptibilities, clinical
      characteristics, carbapenem use for empirical and definitive treatment, and
      mortality rates between the two groups. Eighteen IMP-8 producers could be deemed
      as resistant to all carbapenems [minimum inhibitory concentration (MIC) of any
      carbapenem >=2 MUg/mL]; patients with these isolates had a lower, but non
      significant, 28-day mortality rate (27.8 %) than patients infected with non-MBL
      producers having similar carbapenem MICs (39.0 %) (p = 0.41). A multivariate
      analysis revealed severity of acute illness as the single independent variable
      associated with both 7-day and 28-day mortality rates (p < 0.01) for infections
      caused by Enterobacteriaceae with decreased carbapenem susceptibilities. Our
      findings suggest that the clinical detection of IMP-producing Enterobacteriaceae
      is not required even when the "old" CLSI criteria are used.

PMID- 23001512
TI  - The strongest resistance of Staphylococcus aureus to erythromycin is caused by
      decreasing uptake of the antibiotic into the cells.
AB  - The consequence of excessive use of macrolides is a high occurrence of mechanisms
      responsible for resistance to these drugs. Of 97 erythromycin-resistant bacterial
      strains gathered in the Wroclaw area in Poland, 60% exhibited very high
      resistance, and those with the inducible MLS(B) (macrolide-lincosamide
      streptogramin B) resistance phenotype predominated. Direct genetic investigation
      revealed that the erm genes coding for ribosomal methylases are the most
      frequently occurring erythromycin resistance-determining genes. No genetic
      resistance determinant was detected in 13% of the erythromycin-resistant strains.
      The efflux mechanism occurs in strains isolated from the nasopharyngeal cavity
      twice as often as in those isolated from other material, where the mechanism
      connected with target site modification predominates. Measurements of
      radiolabelled antibiotic accumulation inside bacterial cells revealed that in
      highly resistant strains (MIC > 1024 MUg/ml), an important factor responsible for
      the resistance is the permeability barrier at the cell wall level. This would be
      a hitherto unknown mechanism of resistance to erythromycin in Staphylococcus
      aureus.

PMID- 23001513
TI  - PUMA, a critical mediator of cell death--one decade on from its discovery.
AB  - PUMA (p53 upregulated modulator of apoptosis) is a pro-apoptotic member of the
      BH3-only subgroup of the Bcl-2 family. It is a key mediator of p53-dependent and
      p53-independent apoptosis and was identified 10 years ago. The PUMA gene is
      mapped to the long arm of chromosome 19, a region that is frequently deleted in a
      large number of human cancers. PUMA mediates apoptosis thanks to its ability to
      directly bind known anti-apoptotic members of the Bcl-2 family. It mainly
      localizes to the mitochondria. The binding of PUMA to the inhibitory members of
      the Bcl-2 family (Bcl-2-like proteins) via its BH3 domain seems to be a critical
      regulatory step in the induction of apoptosis. It results in the displacement of
      the proteins Bax and/or Bak. This is followed by their activation and the
      formation of pore-like structures on the mitochondrial membrane, which
      permeabilizes the outer mitochondrial membrane, leading to mitochondrial
      dysfunction and caspase activation. PUMA is involved in a large number of
      physiological and pathological processes, including the immune response, cancer,
      neurodegenerative diseases and bacterial and viral infections.

PMID- 23001514
TI  - Electrochromatography on acrylate-based monolith in cyclic olefin copolymer
      microchip: a cost-effective and easy-to-use technology.
AB  - This article shows that there is great interest in using an
      electrochromatographic microchip made of hexyl acrylate (HA) based porous
      monolith cast within the channel of a cyclic olefin copolymer (COC) device. The
      monolith is simultaneously in situ synthesized and anchored to the inner walls of
      the channel in less than 10 min. By appropriate choice of light intensity used
      during the synthesis, the separation efficiency obtained for nonpolar solutes
      such as polycyclic aromatic hydrocarbons (PAH) is increased up to 250 000
      plates/m. The performance of this HA-filled COC microchip was investigated for a
      wide range of analytes of varying nature. The reversed-phase separation of four
      aflatoxins is obtained in less than 2 min. The baseline separation of a mixture
      of neurotransmitters including six amino acids and two catecholamines is possible
      thanks to the superimposition of the differences in electrophoretic mobility on
      the chromatographic process. The durability of the system at pH 13 allows the
      separation of five biogenic amines and the quantitative determination of two of
      them in numerous wine samples. The feasibility of on-line preconcentration is
      also demonstrated. Hydrophilic surface modification of COC channel via UV
      photografting with poly(ethylene glycol) methacrylate (PEGMA) before in situ
      synthesis of HA, is necessary to reduce the adsorption of very hydrophobic
      solutes such as PAH during enrichment. The detection limit of fluoranthene is
      decreased down to less than 1 ppb with a preconcentration of 4.5 h on the HA
      filled PEGMA functionalized COC microchip.

PMID- 23001515
TI  - Limits on the spatial resolution of monolithic scintillators read out by APD
      arrays.
AB  - Cramer-Rao theory can be used to derive the lower bound on the spatial resolution
      achievable with position-sensitive scintillation detectors as a function of the
      detector geometry and the pertinent physical properties of the scintillator, the
      photosensor and the readout electronics. Knowledge of the Cramer-Rao lower bound
      (CRLB) can for example be used to optimize the detector design and to test the
      performance of the method used to derive position information from the detector
      signals. Here, this approach is demonstrated for monolithic scintillator
      detectors for positron emission tomography. Two detector geometries are
      investigated: a 20 * 10 * 10 mm(3) and a 20 * 10 * 20 mm(3) monolithic
      LYSO:Ce(3+) crystal read out by one or two Hamamatsu S8550SPL avalanche
      photodiode (APD) arrays, respectively. The results indicate that in these
      detectors the CRLB is primarily determined by the APD excess noise factor and the
      number of scintillation photons detected. Furthermore, it is shown that the use
      of a k-nearest neighbor (k-NN) algorithm for position estimation allows the
      experimentally obtained spatial resolution to closely approach the CRLB. The
      approach outlined in this work can in principle be applied to any scintillation
      detector in which position information is encoded in the distribution of the
      scintillation light over multiple photosensor elements.

PMID- 23001516
TI  - Do predictors of incomplete Kawasaki disease exist for infants?
AB  - Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of
      acquired heart disease in infants and young children. However, the diagnosis of
      infantile KD can be difficult or delayed due to vague clinical manifestations.
      This current study aimed to assess the clinical characteristics and cardiac
      complications of infantile KD. The study retrospectively reviewed the data of 242
      patients with KD. The clinical, laboratory, and echocardiographic data between
      infants and older children were analyzed. The patients were divided into two
      groups: infants 12 months old or younger and children older than 12 months. The
      rate of incomplete KD was much more frequent in infants. During all phases,
      prohormone brain natriuretic peptide (Pro-BNP) levels were higher in infants, as
      was thrombocytosis. The coronary artery z-score was higher in infants at all
      phases of KD. On tissue Doppler imaging, the E/E' ratio (ratio of transmitral
      Doppler early filling velocity to tissue Doppler early diastolic mitral annular
      velocity) was higher at the septal and lateral annulus in infants. Infant
      patients with KD are at increased risk for the development of coronary
      abnormalities and diastolic dysfunction. Higher levels of Pro-BNP and
      thrombocytosis with diastolic echo parameters of a higher E/E' ratio can help to
      identify incomplete KD in infants.

PMID- 23001517
TI  - Tissue Doppler imaging detects impaired biventricular performance shortly after
      congenital heart defect surgery.
AB  - Cardiac surgery with cardiopulmonary bypass is associated with the development of
      a systemic inflammatory response, which can lead to myocardial damage. However,
      knowledge concerning the time course of ventricular performance deterioration and
      restoration after correction of a congenital heart defect (CHD) in pediatric
      patients is sparse. Therefore, the authors perioperatively quantified left
      ventricular (LV) and right ventricular (RV) performance using echocardiography.
      Their study included 141 patients (ages 0-18 years) undergoing CHD correction and
      40 control subjects. The study assessed LV systolic performance (fractional
      shortening) and diastolic performance (mitral Doppler flow) in combination with
      RV systolic performance [tricuspid annular plane systolic excursion (TAPSE)] and
      diastolic performance (tricuspid Doppler flow). Additionally, systolic (S') and
      diastolic (E', A', E/E') tissue Doppler imaging (TDI) measurements were obtained
      at the LV lateral wall, the interventricular septum, and the RV free wall.
      Echocardiographic studies were performed preoperatively, 1 day postoperatively,
      and at hospital discharge after 9 +/- 5 days. Although all LV echocardiographic
      measurements showed a deterioration 1 day after surgery, only LV TDI measurements
      were impaired in patients at discharge versus control subjects (S': 5.7 +/- 2.0
      vs 7.1 +/- 2.7 cm/s; E': 9.8 +/- 3.9 vs 13.7 +/- 5.1 cm/s; E/E': 12.2 +/- 6.4 vs
      8.8 +/- 4.3; p < 0.05). In the RV, TAPSE and RV TDI velocities also were impaired
      in patients at discharge versus control subjects (TAPSE: 9 +/- 3 vs 17 +/- 5 mm;
      S': 5.2 +/- 1.7 vs 11.4 +/- 3.4 cm/s; E': 7.3 +/- 2.5 vs 16.3 +/- 5.2 cm/s; E/E':
      12.5 +/- 6.8 vs 4.8 +/- 1.9; p < 0.05). Furthermore, longer aortic cross-clamp
      times were associated with more impaired postoperative LV and RV performance (p <
      0.05). In conclusion, both systolic and diastolic biventricular performances were
      impaired shortly after CHD correction. This impairment was detected only by TDI
      parameters and TAPSE. Furthermore, a longer-lasting negative influence of
      cardiopulmonary bypass on myocardial performance was suggested.

PMID- 23001518
TI  - Enhanced resistance against Thielaviopsis basicola in transgenic cotton plants
      expressing Arabidopsis NPR1 gene.
AB  - Black root rot, caused by Thielaviopsis basicola, is an important disease in
      several crops including cotton. We studied the response of Arabidopsis NPR1
      (AtNPR1)-expressing cotton lines, previously shown to be highly resistant to a
      diverse set of pathogens, to a challenge from T. basicola. In four different
      experiments, we found significant degree of tolerance in the transgenic lines to
      black root rot. Although transformants showed the typical root discoloration
      symptoms similar to the wild-type control plants following infection, their roots
      tended to recover faster and resumed normal growth. Better performance of
      transgenic plants is reflected by the fact that they have significantly higher
      shoot and root mass, longer shoot length, and greater number of boll-set.
      Transcriptional analysis of the defense response showed that the roots of AtNPR1
      overexpressing transgenic plants exhibited stronger and faster induction of most
      of these defense-related genes, particularly PR1, thaumatin, glucanase, LOX1, and
      chitinase. The results obtained in this investigation provide further support for
      a broad-spectrum nature of the resistance conferred by overexpression of AtNPR1
      gene in cotton.

PMID- 23001519
TI  - Native-sized spider silk proteins synthesized in planta via intein-based
      multimerization.
AB  - The synthesis of native-sized proteins is a pre-requisite for exploiting the
      potential of spider silk as a bio-based material. The unique properties of spider
      silk, such as extraordinary tensile strength and elasticity, result from the
      highly repetitive nature of spider silk protein motifs. The present report
      describes the combination of spider silk flagelliform protein (FLAG) production
      in the endoplasmic reticulum of tobacco plant leaf cells with an intein-based
      posttranslational protein fusion technology. The repeated ligation of FLAG
      monomers resulted in the formation of large multimers. This method avoids the
      need for highly repetitive transgenes, which may result in a higher genetic and
      transcriptional stability. Here we show, for the first time, the production of
      synthetic, high molecular weight spider silk proteins larger than 250 kDa based
      on the assembly of protein monomers via intein-mediated trans-splicing in planta.
      The resulting multimeric structures form microfibers, thereby demonstrating their
      great potential as a biomaterial.

PMID- 23001520
TI  - Abdominal wall phlebitis due to Prevotella bivia following renal transplantation
      in a patient with an occluded inferior vena cava.
AB  - Pre-existing occlusion of the inferior vena cava may complicate renal
      transplantation. Suppurative abdominal wall phlebitis following renal
      transplantation was diagnosed in a patient with pre-existing thrombosis of the
      inferior vena cava of unknown cause. The phlebitis developed in the subcutaneous
      collateral veins of the abdominal wall contra-laterally to the renal transplant.
      Cultures from abdominal wall micro-abscesses yielded Prevotella bivia as the
      causative agent. This complication has not been described before in the context
      of renal transplantation. The pathogenesis and management of this serious
      complication are discussed in this paper.

PMID- 23001521
TI  - In situ hybridization assay-based small molecule screening in zebrafish.
AB  - In vitro biochemical and cell-based small molecule screens have been widely used
      to identify compounds that target specific signaling pathways. But the identified
      compounds frequently fail at the animal testing stage, largely due to the in vivo
      absorption, metabolism and toxicity of chemicals. Zebrafish has recently emerged
      as a vertebrate whole organism model for small molecule screening. The in vivo
      bioactivity and specificity of compounds are examined from the very beginning of
      zebrafish screens. In addition, zebrafish is suitable for chemical screens at a
      large scale similar to cellular assays. This protocol describes an approach for
      in situ hybridization (ISH)-based chemical screening in zebrafish, which, in
      principle, can be used to screen any gene product. The described protocol has
      been used to identify small molecules affecting specific molecular pathways and
      biological processes. It can also be adapted to zebrafish screens with different
      readouts.

PMID- 23001522
TI  - Alcohol consumption and the risk of stroke among hypertensive and overweight men.
AB  - High blood pressure and overweight are risk factors for stroke. The aim of the
      present study was to examine the association between alcohol consumption and the
      risk of stroke according to the level of blood pressure and body weight. This
      study is a population-based sample of men with an average follow-up of 14.9 years
      from eastern Finland. A total of 2,599 men with no history of stroke at baseline
      participated. During the follow-up period, 224 strokes occurred, of which 181
      were ischemic strokes. After adjustment for age, year of examination,
      socioeconomic status, serum LDL cholesterol, body mass index, smoking and energy
      expenditure of physical activity (kcal/day), there was a significant trend of an
      increased risk for any and ischemic stroke among hypertensive men. Hypertensive
      (blood pressure of over 140/90 mm Hg) men, who did not consume alcohol had a 1.72
      fold (95 % CI 1.12-2.66; p = 0.014) relative risk (RR) for any stroke and a 1.90
      fold (95 % CI 1.15-3.13; p = 0.012) RR for ischemic stroke. Among hypertensive
      men who consumed alcohol RR was 1.86-fold (95 % CI 1.20-2.89; p = 0.005) for any
      stroke and 2.02-fold (95 % CI 1.21-3.35; p = 0.007) for ischemic stroke. Men who
      did not consume alcohol with elevated BMI (>=26.4 kg/m(2)) had a 1.63-fold RR (95
      % CI 1.11-2.40; p = 0.013) for any stroke and a 1.33-fold RR (95 % CI 0.87-2.04;
      p = 0.199) for ischemic stroke after adjusting for risk factors. Overweight men
      (>=26.4 kg/m(2)) who consumed alcohol had a 1.73-fold RR (95 % CI 1.18-2.54; p =
      0.005) for any stroke and a 1.71-fold RR (95 % CI 1.14-2.57; p = 0.010) for
      ischemic stroke after being adjusted for risk factors. In conclusion, this
      population-based prospective study shows that hypertensive and overweight men who
      consumed alcohol had an increased risk for stroke.

PMID- 23001523
TI  - Management of status epilepticus.

PMID- 23001524
TI  - Grounding early intervention: physical therapy cannot just be about motor skills
      anymore.
AB  - This perspective article provides support for 4 interrelated tenets: grounded
      perceptual-motor experience within cultural and social contexts forms cognition;
      exploration through early behaviors, such as object interaction, sitting, and
      locomotion, broadly facilitates development; infants and children with limited
      exploration are at risk for global developmental impairments; and early
      interventions targeting exploratory behaviors may be feasible and effective at
      advancing a range of abilities across developmental domains and time. These
      tenets emphasize that through the promotion of early perceptual-motor behaviors,
      broader, more global developmental advancements can be facilitated and future
      delays can be minimized across domains for infants and children with special
      needs. Researchers, educators, and clinicians should build on these tenets to
      further demonstrate the effectiveness of targeted early interventions. The goals
      of these interventions should be not only to advance targeted perceptual-motor
      skills in the moment but also to more broadly advance future abilities and meet
      the early intervention goal of maximizing children's learning potential.

PMID- 23001526
TI  - Delivering the physical therapy value proposition: a call to action.

PMID- 23001525
TI  - Preoperative prediction of ambulatory status at 6 months after total hip
      arthroplasty.
AB  - BACKGROUND: Total hip arthroplasty (THA) is an effective procedure that provides
      patients with long-term relief from pain and enables them to resume their normal
      daily activities. Preoperative instruction about the functional outcomes and
      optimum goal of rehabilitation is helpful for patients undergoing THA. OBJECTIVE:
      The purposes of this study were: (1) to examine the relationships between
      preoperative physical functions and ambulation following THA and (2) to identify
      optimal cutoff values for estimating ambulatory status at 6 months after THA.
      DESIGN: This was a retrospective study. METHODS: The study participants were 204
      patients who underwent a unilateral THA. Hip abductor and knee extensor strength
      were measured and the Timed "Up & Go" Test (TUG) was conducted preoperatively.
      The patients were divided into 2 groups according to self-reported walking
      ability at 6 months postoperatively: an independent ambulation group (n=118) and
      a cane-assisted ambulation group (n=86). Differences between the 2 groups were
      examined using an unpaired t test or the chi-square test. A stepwise multiple
      logistic regression analysis was performed with walking ability at 6 months
      postoperatively as a dependent variable and age, sex, contralateral hip
      osteoarthritis (ie, whether a participant had contralateral hip osteoarthritis or
      not), body mass index, hip abductor strength, knee extensor strength, and TUG
      score as independent variables. Receiver operating characteristic curve analysis
      was used to identify a cutoff point for classifying the participants into the 2
      groups. RESULTS: A stepwise multiple logistic regression analysis selected 3
      factors (age, knee extensor strength, and TUG score) as significant variables
      affecting the midterm ambulatory ability after THA. Moreover, receiver operating
      characteristic curve analyses revealed that the midterm (ie, 6-month) ambulatory
      status after THA was more accurately predicted by the patient's TUG score (cutoff
      point=10 seconds, sensitivity=76.7%, specificity=93.2%, area under the
      curve=0.93) than by age and knee extensor strength. LIMITATIONS: The
      categorization of ambulatory status in this study was based solely on self
      reported walking ability. CONCLUSION: The findings indicate that patients with a
      preoperative TUG score of less than 10 seconds are likely to walk without an
      assistive device at 6 months after THA.

PMID- 23001529
TI  - Acceleration of adventitious shoots by interaction between exogenous hormone and
      adenine sulphate in Althaea officinalis L.
AB  - In the current study attempts were made to investigate the effects of three
      different phases of callus induction followed by adventitious regeneration from
      leaf segments (central and lateral vein). Callus induction was observed in
      Murashige and Skoog's (MS) medium supplemented with 15.0 MUM 2,4-dichloro phenoxy
      acetic acid (2,4-D). Adventitious shoot buds formation was achieved on MS medium
      supplemented with 7.5 MUM 2,4-D and 20.0 MUM AdS in liquid medium as it induced
      19.2 +/- 0.58 buds in central vein explants. Addition of different growth
      regulators (cytokinins-6-benzyladenine, kinetin and 2-isopentenyl adenine alone
      or in combination with auxins-indole-3-acetic acid, indole-3-butyric acid and
      alpha-naphthalene acetic acid, improved the shoot regeneration efficiency, in
      which 5.0 MUM 6-benzyl adenine along with 0.25 MUM alpha-naphthalene acetic acid
      was shown to be the most effective medium for maximum shoot regeneration (81.3 %)
      with 24.6 number of shoots and 4.4 +/- 0.08 cm shoot length per explant. Leaf
      culture of central veins led to better shoot formation capacity in comparison to
      lateral vein. Rooting was readily achieved on the differentiated shoots on 1/2 MS
      medium augmented with 20.0 MUM indole-3-butyric acid. The plants were
      successfully hardened off in sterile soilrite followed by their establishment in
      garden soil with 80 % survival rate.

PMID- 23001527
TI  - Artificial neural network modeling of dissolved oxygen in the Heihe River,
      Northwestern China.
AB  - Identification and quantification of dissolved oxygen (DO) profiles of river is
      one of the primary concerns for water resources managers. In this research, an
      artificial neural network (ANN) was developed to simulate the DO concentrations
      in the Heihe River, Northwestern China. A three-layer back-propagation ANN was
      used with the Bayesian regularization training algorithm. The input variables of
      the neural network were pH, electrical conductivity, chloride (Cl(-)), calcium
      (Ca(2+)), total alkalinity, total hardness, nitrate nitrogen (NO3-N), and
      ammonical nitrogen (NH4-N). The ANN structure with 14 hidden neurons obtained the
      best selection. By making comparison between the results of the ANN model and the
      measured data on the basis of correlation coefficient (r) and root mean square
      error (RMSE), a good model-fitting DO values indicated the effectiveness of
      neural network model. It is found that the coefficient of correlation (r) values
      for the training, validation, and test sets were 0.9654, 0.9841, and 0.9680,
      respectively, and the respective values of RMSE for the training, validation, and
      test sets were 0.4272, 0.3667, and 0.4570, respectively. Sensitivity analysis was
      used to determine the influence of input variables on the dependent variable. The
      most effective inputs were determined as pH, NO3-N, NH4-N, and Ca(2+). Cl(-) was
      found to be least effective variables on the proposed model. The identified ANN
      model can be used to simulate the water quality parameters.

PMID- 23001530
TI  - Elicitation of andrographolide in the suspension cultures of Andrographis
      paniculata.
AB  - Andrographis paniculata belonging to the family Acanthaceae produces a group of
      diterpene lactones, one of which is the pharmaceutically important
      andrographolide. It is known to possess various important biological properties
      like anticancer, anti-HIV, anti-inflammatory, etc. This is the first report on
      the production of andrographolide in the cell suspension cultures of Andrographis
      paniculata by 'elicitation'. Elicitation was attempted to enhance the
      andrographolide content in the suspension cultures of Andrographis paniculata and
      also to ascertain its stimulation under stress conditions or in response to
      pathogen attack. The maximum andrographolide production was found to be 1.53 mg/g
      dry cell weight (DCW) at the end of stationary phase during the growth curve. The
      biotic elicitors (yeast, Escherichia coli, Bacillus subtilis, Agrobacterium
      rhizogenes 532 and Agrobacterium tumefaciens C 58) were more effective in
      eliciting the response when compared to the abiotic elicitors (CdCl(2), AgNO(3),
      CuCl(2) and HgCl(2)). Yeast has shown to stimulate maximum accumulation of 13.5
      mg/g DCW andrographolide, which was found to be 8.82-fold higher than the
      untreated cultures.

PMID- 23001531
TI  - Evidence showing duplication and recombination of cel genes in tandem from
      hyperthermophilic Thermotoga sp.
AB  - This study was conducted to assess the gene duplication and diversification of
      tandem cellulase genes in thermophilic bacteria. The tandem cellulase genes cel5C
      and cel5D were cloned from Thermotoga maritima MSB8, and a survey of the
      thermophilic bacterial genome for tandem cel genes from the databases was carried
      out. A clone having 2.3 kb fragment from T. maritima MSB8 showed cellulase
      activity, which had two open reading frames in tandem (cel5C and cel5D). The
      cel5C gene has 954 bp, which encodes a protein of 317 amino acid residues with a
      signal peptide of 23 amino acids, and the other gene cel5D consisting of 990 bp
      encoding a protein of 329 amino acid residues. These two proteins have similarity
      with the enzymes of glycosyl hydrolase family 5. From the enzyme assay, it was
      observed that Cel5C was extracellular and Cel5D was intracellular cellulase.
      Phylogenetic and homology matrix analyses of DNA and protein sequences revealed
      that family 12 cellulase enzymes Cel12A and Cel12B displayed higher homology (>50
      %), but Cel5C and Cel5D enzymes belong to family 5 displayed lower homology (<30
      %). In addition, repeated and mirror sequences in tandem genes are supposed to
      show the existence of gene duplication and recombination.

PMID- 23001532
TI  - Composite small cell and mucinous carcinoma originating from the intrahepatic
      bile duct: report of a case.
AB  - The biliary tract is a very rare site for the occurrence of extrapulmonary small
      cell carcinoma. A 68-year-old Japanese female was being followed up for
      autoimmune hepatitis, and was referred to our hospital because segmental
      intrahepatic bile duct dilation was found on routine imaging studies, suggesting
      intrahepatic cholangiocarcinoma. She underwent left lobectomy of the liver and
      concomitant resection of the caudate lobe. Microscopic examination of the
      explanted liver showed a primary composite tumor comprising small cell and
      mucinous carcinomas that originated in the intrahepatic bile duct. Further
      immunohistochemical studies, including cytokeratin-19 and chromogranin-A
      staining, showed the two cellular components of the tumor to have similar
      characteristics. The amphicrine properties indicated that the tumor had a
      monoclonal origin but with biphenotypic differentiation, which was responsible
      for the histogenesis of this tumor.

PMID- 23001533
TI  - The current diagnosis and treatment of benign biliary stricture.
AB  - PURPOSE: As laparoscopic cholecystectomy and liver transplantation (LT) have
      become more common, so has biliary stricture. Fortunately, endoscopic treatment
      has almost simultaneously been developed. This article reviews the recent reports
      concerning the management of benign biliary strictures (BBS). METHODS: The
      literature regarding the diagnosis and treatment of BBS is reviewed after an
      electronic search of PubMed from 1982 to 2009 was performed. RESULTS: Despite the
      existence of diagnostic tools including tumor markers, brush cytology,
      intraductal ultrasonography and other imaging modalities, differentiating BBS
      from malignant stricture remains challenging, as does differentiating IgG4
      related sclerosing cholangitis from other benign strictures. Endoscopic treatment
      with balloon dilation of the stricture and serial insertions of stents is the
      preferred initial treatment for BBS. However, the outcomes of endoscopic
      treatments for primary sclerosing cholangitis or chronic pancreatitis are poorer
      than those for post-surgical biliary stricture. When endoscopic treatments fail
      to repair complicated biliary strictures such as Bismuth types III, IV, and V,
      surgical repair is recommended. Among the non-anastomotic BBS, intrahepatic
      bilateral type strictures after LT may require repeat transplantation.
      CONCLUSION: Early referral to tertiary centers with an alliance among
      hepatobiliary surgeons, interventional radiologists, and endoscopists is
      necessary to assure optimal results.

PMID- 23001534
TI  - Combined resection of a tumor and the inferior vena cava: report of two cases.
AB  - Tumor resection and caval tumor thrombectomy, with or without cavotomy and
      inferior vena cava (IVC) replacement are sometimes performed in patients with
      renal cell carcinoma (RCC) extending into the IVC or liver tumors invading the
      IVC. Two such cases were treated. Case 1: a 68-year-old female was transferred
      with a diagnosis of right RCC with tumor thrombus extending into the IVC. A
      plication was performed to prevent extension into the right atrium before the
      nephrectomy and cavotomy with removal of the tumor thrombus was accomplished,
      because the IVC was almost completely obstructed and the hemodynamics were stable
      during cross-clamping of the IVC. Case 2: a 37-year-old female was transferred
      with a diagnosis of a giant metastatic liver tumor. A trisegmentectomy with
      resection of the invaded IVC and IVC replacement was performed while the
      abdominal aorta was cross-clamped to maintain the hemodynamics. Therefore,
      abdominal aortic cross-clamping was convenient to maintain the hemodynamics when
      the IVC replacement was performed during IVC cross-clamping. 

PMID- 23001535
TI  - Comparative study of wheat low-molecular-weight glutenin and alpha-gliadin
      trafficking in tobacco cells.
AB  - KEY MESSAGE : Wheat low-molecular-weight-glutenin and alpha-gliadin were
      accumulated in the endoplasmic reticulum and formed protein body-like structures
      in tobacco cells, with the participation of BiP chaperone. Possible interactions
      between these prolamins were investigated. Wheat prolamins are the major proteins
      that accumulate in endosperm cells and are largely responsible for the unique
      biochemical properties of wheat products. They are accumulated in the endoplasmic
      reticulum (ER) where they form protein bodies (PBs) and are then transported to
      the storage vacuole where they form a protein matrix in the ripe seeds. Whereas
      previous studies have been carried out to determine the atypical trafficking
      pathway of prolamins, the mechanisms leading to ER retention and PB formation are
      still not clear. In this study, we examined the trafficking of a low-molecular
      weight glutenin subunit (LMW-glutenin) and alpha-gliadin fused to fluorescent
      proteins expressed in tobacco cells. Through transient transformation in
      epidermal tobacco leaves, we demonstrated that both LMW-glutenin and alpha
      gliadin were retained in the ER and formed mobile protein body-like structures
      (PBLS) that generally do not co-localise with Golgi bodies. An increased
      expression level of BiP in tobacco cells transformed with alpha-gliadin or LMW
      glutenin was observed, suggesting the participation of this chaperone protein in
      the accumulation of wheat prolamins in tobacco cells. When stably expressed in BY
      2 cells, LMW-glutenin fusion was retained longer in the ER before being exported
      to and degraded in the vacuole, compared with alpha-gliadin fusion, suggesting
      the involvement of intermolecular disulphide bonds in ER retention, but not in
      PBLS formation. Co-localisation experiments showed that gliadins and LMW-glutenin
      were found in the same PBLS with no particular distribution, which could be due
      to their ability to interact with each other as indicated by yeast two-hybrid
      assays.

PMID- 23001537
TI  - The potential role of ozone in ameliorating the age-related biochemical changes
      in male rat cerebral cortex.
AB  - Controlled ozone (O(3)) administration is known to promote oxidative
      preconditioning and, thus, may reverse chronic oxidative stress that accompanies
      aging. Therefore, the present work was undertaken to study the potential role of
      O(3) in ameliorating certain age-related biochemical changes represented by
      impaired activities of inner mitochondrial membrane enzymes, compromised energy
      production and increased oxidative burden in male rat cerebral cortex.
      Prophylactic administration of O(3)-O(2) mixture to 3 month-old rats, at an
      intrarectal dose of 0.6 mg O(3) kg(-1) body weight twice/week for 3 months then
      once/week until the age of 15 months, normalized reduced glutathione content,
      adenosine triphosphate/adenosine diphosphate ratio, mitochondrial superoxide
      dismutase (SOD) and complex IV (cytochrome-c oxidase) activities, improved
      glutathione redox index (GSHRI), complex I (NADH-ubiquinone oxidoreductase) and
      mitochondrial nitric oxide synthase (mtNOS) activities, and attenuated the rise
      in malondialdehyde (MDA) and mitochondrial protein carbonyl levels. On the other
      hand, therapeutic administration of the same dose of O(3)-O(2) mixture to 14
      month-old rats three times/week for 1 month, reduced mitochondrial protein
      carbonyl level only. Other favorable effects, including normalization of Na,K
      adenosine triphosphatase (Na,K-ATPase) activity and reduction in lipofuscin level
      in the prophylactic group, as well as improvement in mitochondrial SOD and
      complex I activities with a decrease in total MDA level in the therapeutic group,
      were comparable to the effects observed in the corresponding O(2)-treated control
      groups. In conclusion, the present study revealed that prophylactic
      administration of O(3)-O(2) mixture provided better amelioration of age-related
      cerebrocortical alterations by combining the advantages of both O(3) and O(2)
      therapies.

PMID- 23001538
TI  - Lurasidone in schizophrenia: new information about dosage and place in therapy.
AB  - Lurasidone is a newer "atypical" or "secondgeneration" antipsychotic that has
      received regulatory approval in the US and Canada for the treatment of
      schizophrenia. Recent changes in lurasidone product labeling include an expansion
      of the recommended dose range from 40-80 mg/day to 40-160 mg/day, administered
      once-daily with food. The recommended starting dose is 40 mg/day. Initial dose
      titration is not required. Efficacy for the treatment of acute episodes of
      schizophrenia was established in five, 6-week, fixed-dose, randomized, placebo
      controlled trials. Additional short-term studies in patients with schizophrenia
      include a 3-week, randomized, double-blind trial comparing lurasidone with
      ziprasidone on safety and tolerability outcomes, and a 6-week, randomized, open
      label switch study. Available long-term data includes a 12-month, doubleblind
      safety and tolerability study comparing lurasidone with risperidone; a 6-month,
      openlabel extension study for one of the shortterm registration studies where
      patients were initially randomized to receive lurasidone, olanzapine, or placebo;
      and a 12-month, doubleblind extension study comparing lurasidone with quetiapine
      extended-release after having received lurasidone, quetiapine extendedrelease, or
      placebo for 6 weeks. The totality of the evidence supports the overall
      tolerability of lurasidone, with minimal weight gain and no clinically-meaningful
      alterations in glucose, lipids, or the electrocardiogram corrected QT (ECG QTc)
      interval. The most commonly encountered adverse events that can be observed with
      lurasidone are somnolence, akathisia, nausea, and parkinsonism. Additional
      clinical trials are underway for the use of lurasidone in patients with bipolar
      disorder, including major depressive episodes in patients with bipolar I
      disorder, and in bipolar and schizophrenia maintenance. Principal advantages over
      some other second-generation antipsychotics are lurasidone's highly favorable
      metabolic profile and once-daily dosing regimen. Additional studies are desirable
      to directly compare and contrast lurasidone's efficacy with other antipsychotic
      agents.

PMID- 23001540
TI  - Effect of resinous extract from Commiphora swynnertonii (Burrt) on experimental
      coccidial infection in chickens.
AB  - A crude resinous extract from Commiphora swynnertonii was tested against an
      experimental coccidial infection in local chickens. A total of 80 growing
      chickens were randomly assigned into five groups, which received different
      treatments. Chickens in G1 were not infected with coccidian oocysts and therefore
      served as a negative control. All chickens in G2, G3, G4 and G5 were infected
      through oral administration of coccidian oocysts suspension at a dosed rate of
      1.5 * 10(4) Eimeria spp. oocysts per bird. Starting from day 3 post-infection
      (p.i), chickens in different groups were treated for 7 consecutive days as
      follows: G1 and G2 (positive control) received 5 ml of normal saline as placebo,
      G3 and G4 were given the extract at 400 and 800 mg/kg bodyweight whereas G5
      received anticoccidial drug. Clinical signs, bodyweights, oocysts counts and
      mortality rates were observed regularly. Results showed that oral administration
      of the resinous extract to chickens with coccidiosis significantly reduced
      mortality rate from 94 to 25 % and oocysts counts from 1.03 * 10(5) to 6.55 *
      10(3) oocysts/g faeces (p < 0.05). Also a body condition score chart indicated
      less severe clinical signs of the disease in the groups which received the
      extract. Mean daily body weights were slightly reduced by the administration of
      the extract but this effect disappeared by day 7 p.i. These findings clearly
      indicate that resinous extract from C. swynnertonii has significant anticoccidial
      effect against experimental Eimeria spp. infection in chickens. A larger field
      trial to validate the use of the extract in chickens naturally infected with
      Eimeria spp. is required.

PMID- 23001541
TI  - Awareness and knowledge of sexually transmitted diseases among secondary school
      students in two German cities.
AB  - Several western countries have reported increases of sexually transmitted
      diseases such as gonorrhea, syphilis and chlamydia since the mid-1990s,
      especially among teenagers 16-19 years old. We conducted a school-based survey to
      assess awareness and knowledge of STDs among students attending the 8th grade and
      above in Bremen and Bremerhaven, two cities in northern Germany. Between October
      and December 2011 students completed an anonymous questionnaire on awareness and
      knowledge of STDs in 8 different schools. To assess awareness of STDs, the
      students were asked to indicate which STDs they had heard of. Knowledge of STDs
      was assessed based on 4 general questions. Furthermore, comprehensive awareness
      of HPV was assessed based on 3 items. We assessed differences in HPV awareness
      and knowledge of STDs by key demographic variables such as age, gender and
      migrant background. A total of 1,148 students aged 12-20 years (response 28 %)
      completed the questionnaire. 31 % had a migrant background and 55 % were girls.
      Almost all students had heard of HIV/AIDS, but only 23 % of chlamydia and 13 % of
      HPV. Significantly more girls than boys had heard of HPV (18 vs. 8 %) and
      chlamydia (31 vs. 16 %). Generally, low levels of STD knowledge and awareness of
      HPV were observed. In multivariable analyses, age, gender, and ever having had
      sex were associated with both STD knowledge and awareness of HPV. HIV/AIDS
      remains the only sexually transmitted disease most students have heard of. Sex
      education at school needs to be broadened to include STDs other than HIV/AIDS.

PMID- 23001542
TI  - Trends in outpatient antibiotic use in Israel during the years 2000-2010: setting
      targets for an intervention.
AB  - PURPOSE: The abundant use of antibiotics (Abs) in the community plays a major
      role in inducing Ab resistance, but the literature concerning patterns in
      outpatient Ab use is limited. This study aims to lay the foundations for future
      policy and interventional programs to address the rise in Ab resistance by
      looking at long-term trends in Ab usage in Israel. METHODS: Defined daily doses
      per 1,000 inhabitants per day (DID) of total Ab use, consumption in different age
      groups, and of different Ab preparations were calculated for the years 2000,
      2005, and 2010 in the eight districts of Israel. Data were collected from the
      pharmacy registries of "Clalit Health Services", the largest Health Maintenance
      Organization (HMO) in Israel, covering 4 million patients, representing 53 % of
      the population. Trends in use over time were analyzed. RESULTS: The overall Ab
      usage in Israel has remained constant in the last decade. Three significant
      trends were identified in this study: an increase in the consumption of
      expensive, broad-spectrum Abs, paralleled by a reduction in narrow-spectrum Abs;
      an increase in Ab consumption among the elderly, counteracted by reduced usage
      among children; large regional variations in the overall and specific use of Ab
      agents. CONCLUSIONS: Our main findings of increased broad-spectrum Ab
      consumption, primarily among the adult population in Israel, and a wide
      variability in Ab use between the regions in Israel, can focus our future studies
      on searching for the factors behind these trends to aid in constructing
      interventional methods for decreasing outpatient Ab overuse.

PMID- 23001543
TI  - Extrapulmonary mycobacterial infections in a cohort of HIV-positive patients:
      ultrasound experience from Vicenza, Italy.
AB  - PURPOSE: Extrapulmonary tuberculosis (EPTB) is frequently seen in human
      immunodeficiency virus (HIV)-infected individuals in Sub-Saharan Africa and
      recent work has shown point-of-care (POC) ultrasound to be a diagnostic aid in
      the resource-limited, highly endemic setting. Its role in industrialized
      countries, however, has rarely been studied. With international migration, EPTB
      is increasingly seen in European hospitals. This study reports ultrasound
      findings and discusses the diagnostic relevance of EPTB in an industrialized
      country setting. METHODS: In this retrospective study, we describe a cohort of 27
      patients with a predominantly immigrant background diagnosed with HIV and EPTB in
      Northern Italy and evaluate the role of ultrasound in their clinical management.
      All inpatient files of HIV-positive individuals admitted to our hospital with
      culture-proven diagnosis of EPTB were reviewed, along with chest X-rays and
      ultrasound studies. The outcome and results of long-term follow-up were
      extracted. RESULTS: A total of 243 HIV-positive inpatients were identified
      between January 2005 and November 2011. Twenty-seven of the patients [11.1 %, 95
      % confidence interval (CI) 7.4-15.7] were diagnosed with EPTB. Ultrasound showed
      a typical pattern of enlarged abdominal lymph nodes and focal lesions in the
      spleen and liver in 22 patients (81.5 %, 95 % CI 7.4-15.7) and, thus, helped to
      raise the suspicion of mycobacterial infection. CONCLUSION: As disseminated
      mycobacterial infections in HIV-positive patients can be treated effectively if
      diagnosed early, and typical sonographic findings are seen in the majority of
      these patients, we suggest that POC ultrasound should be integrated in diagnostic
      and screening algorithms for EPTB in developed countries.

PMID- 23001544
TI  - Rare pediatric rhino-orbital infection caused by Saksenaea vasiformis.
AB  - Rhinosinusitis infection due to Saksenaea vasiformis is extremely rare. The
      present case describes a rhino-orbital infection in a 21-month-old Chadian
      immunocompetent male child with a 2-month history of excessive tearing from the
      right eye, followed by swelling of the right upper and lower eye lids, associated
      with right facial swelling and dark coloration surrounding the lower eye lid.
      Coronal computed tomography (CT) scan of the paranasal sinuses showed
      opacification of the right nasal cavities with extension to the orbit. Non
      septate fungal hyphae were diagnosed by tissue sections and a Blankophor P
      fluorescent stain microscopy. The culture grew zygomycetes, S. vasiformis that
      failed to sporulate on Sabouraud dextrose agar, the organism was sporulated after
      1 week on Czapek agar medium, and produced flask-shaped brown pigmented
      sporangium with lateral rhizoids and hemispherical columella filled with spores.
      The patient underwent a right functional endoscopic sinus surgery, where
      debridement of both right maxillary and ethmoid sinuses was done. Treatment with
      amphotericin B lipid complex was started and continued for 41 days. The patient
      was clinically doing better with decreased eye and facial swelling, and his
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were decreased
      to normal values. The patient continued with treatment on posaconazole after his
      discharge, and his condition resolved without further sequelae. Rhinosinusitis
      due to mucormycosis should be considered in any patient, even in young children,
      presenting with progressive rhinosinusitis infection, whether immunocompromised
      or not. Early diagnosis may lead to a successful treatment and good prognosis.

PMID- 23001545
TI  - In-beam quality assurance using induced beta(+) activity in hadrontherapy: a
      preliminary physical requirements study using Geant4.
AB  - Light and heavy ions particle therapy, mainly by means of protons and carbon
      ions, represents an advantageous treatment modality for deep-seated and/or
      radioresistant tumours. An in-beam quality assurance principle is based on the
      detection of secondary particles induced by nuclear fragmentations between
      projectile and target nuclei. Three different strategies are currently under
      investigation: prompt gamma rays imaging, proton interaction vertex imaging and
      in-beam positron emission tomography. Geant4 simulations have been performed
      first in order to assess the accuracy of some hadronic models to reproduce
      experimental data. Two different kinds of data have been considered: beta(+)
      emitting isotopes and prompt gamma-ray production rates. On the one hand
      simulations reproduce experimental beta(+) emitting isotopes production rates to
      an accuracy of 24%. Moreover simulated beta(+) emitting nuclei production rate as
      a function of depth reproduce well the peak-to-plateau ratio of experimental
      data. On the other hand by tuning the tolerance factor of the photon evaporation
      model available in Geant4, we reduce significantly prompt gamma-ray production
      rates until a very good agreement is reached with experimental data. Then we have
      estimated the total amount of induced annihilation photons and prompt gamma rays
      for a simple treatment plan of ~1 physical Gy in a homogenous equivalent soft
      tissue tumour (6 cm depth, 4 cm radius and 2 cm wide). The average annihilation
      photons emitted during a 45 s irradiation in a 4 pi solid angle are ~2 * 10(6)
      annihilation photon pairs and 10(8) single prompt gamma whose energy ranges from
      a few keV to 10 MeV.

PMID- 23001546
TI  - Reduced plasma ghrelin levels on day 1 after esophagectomy: a new predictor of
      prolonged systemic inflammatory response syndrome.
AB  - BACKGROUND AND PURPOSE: Ghrelin, a stomach-derived hormone, stimulates growth
      hormone secretion and appetite, and inhibits excessive inflammatory response.
      Plasma ghrelin might affect the inflammatory response to stressful surgical
      interventions. The aim of this study was to investigate the relationship between
      serial changes in plasma ghrelin concentrations and the postoperative clinical
      course after esophagectomy. METHODS: The prospective cohort study subjects were
      20 patients with esophageal cancer, who underwent esophagectomy with gastric tube
      reconstruction. Blood samples were taken six times perioperatively during the
      course of esophagectomy. RESULTS: The plasma ghrelin level decreased to 33 %
      (range 15-90 %) on postoperative day (POD) 1, relative to the preoperative level,
      then recovered to about 50 % by POD 3-10. The duration of systemic inflammatory
      response syndrome (SIRS) was significantly longer in patients with a marked
      ghrelin reduction to <33 % on POD 1, than in those with less marked reduction of
      >= 33 % (6.1 +/- 1.3 vs. 2.1 +/- 0.6 days, P = 0.019). On POD 1, the only
      inflammatory marker that correlated with the duration of SIRS was the % ghrelin,
      whereas C-reactive protein, leukocyte count, and IL-6 did not. CONCLUSION: An
      early postoperative drop in plasma ghrelin correlated with prolonged SIRS after
      esophagectomy. Thus, the supplementation of low plasma ghrelin may help minimize
      excess inflammatory response in these patients.

PMID- 23001547
TI  - Time limited immunomodulatory functions of transplanted neural precursor cells.
AB  - Fetal neural stem/precursor cells (NPCs) possess powerful immunomodulatory
      properties which enable them to protect the brain from immune-mediated injury. A
      major issue in developing neural stem/precursor cell (NPC) therapy for chronic
      neuroinflammatory disorders such as multiple sclerosis is whether cells maintain
      their immune-regulatory properties for prolonged periods of time. Therefore, we
      studied time-associated changes in NPC immunomodulatory properties. We examined
      whether intracerebrally-transplanted NPCs are able to inhibit early versus
      delayed induction of autoimmune brain inflammation and whether allogeneic NPC
      grafts continuously inhibit host rejection responses. In two experimental
      designs, intraventricular fetal NPC grafts attenuated clinically and
      pathologically brain inflammation during early EAE relapse but failed to inhibit
      the disease relapse if induced at a delayed time point. In correlation, long-term
      cultured neural precursors lost their capacity to inhibit immune cell
      proliferation in vitro. Loss of NPC immune functions was associated with
      transition into a quiescent undifferentiated state. Also, allogeneic fetal NPC
      grafts elicited a strong immune reaction of T cell and microglial infiltration
      and were rejected from the host brain. We conclude that long-term functional
      changes in transplanted neural precursor cells lead to loss of their therapeutic
      immune-regulatory properties, and render allogeneic grafts vulnerable to
      immunologic rejection. Thus, the immunomodulatory effects of neural precursor
      cell transplantation are limited in time.

PMID- 23001548
TI  - Identification of Anopheles daciae in Germany through ITS2 sequencing.
AB  - Until the middle of the twentieth century, malaria was frequently endemic in
      parts of Germany; Anopheles maculipennis complex species were considered the
      primary vectors. Three species of this complex have been identified in Germany:
      A. maculipennis s.s., Anopheles messeae and Anopheles atroparvus; the last
      predominantly from the coastal regions of Northern Germany. Anopheles daciae is a
      recently described member of the A . maculipennis complex and resembles the well
      characterised species A. messeae, although the two species can be distinguished
      through their egg morphology and sequencing of the internal transcribed spacer 2
      (ITS2) region of their nuclear rDNA. In this study, we harvested larval and adult
      mosquito samples from five breeding sites and ten CO(2) trap collection sites in
      the Upper Rhine Valley of Southwestern Germany to analyse the complement of
      anopheline species present. Mosquito ITS2 DNA was extracted and polymerase chain
      reaction (PCR)-amplified using established protocols. Genomic analysis was
      performed by a species-diagnostic restriction fragment length polymorphism assay
      as well as by sequencing of PCR products; the data obtained were aligned against
      nucleic acid sequences from English mosquitoes retrieved from GenBank.
      Additionally, the larval breeding sites of A. messeae were characterised through
      water quality measurement. Forty-seven samples were successfully processed, of
      which 6 were identified as A. daciae and 41 as A. messeae. All samples of A.
      daciae, which has not previously been found in Central Europe, originated from
      one CO(2) trap collection site in Dettenheim, close to Karlsruhe, Southwestern
      Germany. The identification of this malarial vector in a novel area may have
      implications for the re-emergence of disease subsequent to climatic changes.

PMID- 23001549
TI  - Triatomicidal effect of new spot-on formulations applied to poultry in semi-field
      conditions.
AB  - Chagas disease is an endemic disease affecting ten million people in the American
      continent. Produced by a parasite transmitted by triatomine insects, the main
      actions for reducing the incidence of this disease are focused on the control of
      insect vectors. This type of control has produced highly effective results within
      rural homes, but not in peridomestic areas (kitchens, warehouses, hen houses and
      other buildings not attached to the houses). The object of the present study was
      to assess the triatomicidal effect of new spot-on formulations developed by our
      laboratory in a semi-rural environment. The active ingredients of the
      formulations were beta-cypermethrin, pyriproxyfen, or beta-cypermethrin +
      pyriproxyfen. All formulations were applied to hens and tested in miniature
      replicas of rural households where experimental populations of Triatoma
      infestans, the main vector of Chagas disease in Argentina, had been previously
      released. The experimental populations exposed to formulations containing beta
      cypermethrin or beta-cypermethrin + pyriproxyfen were noticeably reduced compared
      to non-treated control groups. However, no differences were observed between the
      effects produced by beta-cypermethrin alone and beta-cypermethrin + pyriproxyfen.
      Pyriproxyfen alone produced no significant reduction in the experimental
      populations of T. infestans. These results suggest that spot-on application of
      beta-cypermethrin could be a useful complementary tool for controlling triatomine
      insects in the peridomestic areas of rural homes.

PMID- 23001550
TI  - In vitro and in vivo treatments of Echinococcus granulosus with Huaier aqueous
      extract and albendazole liposome.
AB  - The aim of this study was to investigate the in vitro and in vivo efficacies of
      chemotherapy employing albendazole liposome (L-ABZ), Huaier aqueous extract, and
      a Huaier aqueous extract/L-ABZ combination against Echinococcus granulosus.
      Protoscolices of E. granulosus were incubated in vitro with the two drugs, either
      separately or in combination, at the following final concentrations: 2 mg/mL
      Huaier aqueous extract, 10 MUg/mL L-ABZ, and 2 mg/mL Huaier aqueous extract + 10
      MUg/mL L-ABZ. Huaier aqueous extract and L-ABZ displayed slower protoscolicidal
      activity when applied separately than when used in combination. The maximum
      protoscolicidal effect was found with the combination Huaier aqueous extract + L
      ABZ. Despite the low Huaier aqueous extract + L-ABZ concentrations used,
      protoscolex viability dropped rapidly. In vivo studies were performed on mice
      injected with protoscolices of E. granulosus. Huaier aqueous extract and L-ABZ
      were administered three times a week for a period of 4 months by the oral route.
      Huaier aqueous extract in E. granulosus-infected mice was effective. Combined
      application of both drugs did increase the treatment efficacy. In conclusion, the
      outcomes obtained clearly demonstrated that in vitro and in vivo treatment with
      Huaier aqueous extract and L-ABZ is effective against E. granulosus.

PMID- 23001551
TI  - Polycyclic aromatic hydrocarbons in surface water and bed sediments of the
      Hungarian upper section of the Danube River.
AB  - This study was performed to elucidate the distribution, concentration trend and
      possible source of polycyclic aromatic hydrocarbons (PAHs) in surface water and
      bed sediments of the Hungarian upper section of the Danube River and the Moson
      Danube branch. A total of 217 samples (water and sediments) were collected from
      four different sampling sites in the period of 2001-2010 and analysed for the 16
      priority US Environmental Protection Agency PAHs. Concentrations of total 16 PAHs
      (?PAHs) in water samples ranged from 25 to 1,208 ng/L, which were predominated by
      two- and three-ring PAHs. The ?PAH concentrations in sediments ranged from 8.3 to
      1,202.5 ng/g dry weight. Four-ring PAHs including fluoranthene and pyrene were
      the dominant species in sediment samples. A selected number of concentration
      ratios of specific PAH compounds were calculated to evaluate the possible sources
      of PAH contamination. The ratios reflected a pattern of pyrogenic input as a
      major source of PAHs. The levels of PAHs determined were compared with other
      sections of the Danube and other regions of the world.

PMID- 23001552
TI  - Utility of cefixime as a complexing reagent for the determination of Ni(II) in
      synthetic mixture and water samples.
AB  - A simple, sensitive, and accurate UV spectrophotometric method has been developed
      for the determination of nickel in synthetic mixture and water samples. The
      method is based on the complexation reaction of nickel ion with cefixime, thus
      leading to the formation of Ni-cefixime complex in ethanol-distilled water medium
      at room temperature. The complex showed the maximum absorption wavelength at 332
      nm. Beer's law is obeyed in the working concentration range of 0.447-4.019 MUg
      mL(-1) with apparent molar absorptivity of 7.314 * 10(3) L mol(-1) cm(-1) and
      Sandell's sensitivity of 0.008 MUg/cm(2)/0.001 absorbance unit. The limits of
      detection and quantitation for the proposed method are 0.016 and 0.054 MUg mL(
      1), respectively. The factors such as cefixime concentration and solvent
      affecting the complexation reaction were carefully studied and optimized. The
      method is validated as per the International Conference on Harmonisation
      guideline. The method is successfully applied to the determination of Ni(II) in
      synthetic mixture and wadi water samples collected from Al Rustaq. The same water
      samples are also analyzed by atomic absorption spectrophotometry. Both methods
      determined the amount of Ni(II) in water sample and found to be approximately the
      same.

PMID- 23001553
TI  - Spatial distribution and source identification of persistent pollutants in marine
      sediments of Hong Kong.
AB  - A data matrix, obtained during a 3-year monitoring period (2007-2009) from 45
      sampling sites in Hong Kong marine, was subjected to determine the spatial
      characterization and identify the sources of main pollutants. Indicator analyses
      indicated that polycyclic aromatic hydrocarbons (PAHs), nickel, manganese, and
      arsenic (As) were at safe levels. Five heavy metals (zinc, lead, cupper, cadmium,
      chromium (Cr)) were moderate to severe enrichment at some sites. Inner Deep Bay
      and Victoria Harbor were considered as hot spots for PAHs and the heavy metals,
      while Tolo Harbor was highly polluted by the heavy metals. Cluster analysis
      classified the 45 sampling sites into three groups, representing different
      pollution levels. Principal component analysis/factor analysis identified four
      principal components (PCs) and explained 84.9 % of the total variances, standing
      for persistent pollution, N factor, P and Cr factor, and As factor, respectively.
      Group A was highly polluted by persistent pollution, group B was the less
      polluted group, and subgroup B1 was less affected by PC3 and PC4 than subgroup
      B2. Group C, considered as the moderately polluted group, was greatly affected by
      N factor or persistent pollution, while subgroup C2 received more N pollution
      than subgroup C1.

PMID- 23001554
TI  - Impact of anthropogenic activities on water quality of Lidder River in Kashmir
      Himalayas.
AB  - The pristine waters of Kashmir Himalaya are showing signs of deterioration due to
      multiple reasons. This study researches the causes of deteriorating water quality
      in the Lidder River, one of the main tributaries of Jhelum River in Kashmir
      Himalaya. The land use and land cover of the Lidder catchment were generated
      using multi-spectral, bi-seasonal IRS LISS III (October 2005 and May 2006)
      satellite data to identify the extent of agriculture and horticulture lands that
      are the main non-point sources of pollution at the catchment scale. A total of 12
      water quality parameters were analyzed over a period of 1 year. Water sampling
      was done at eight different sampling sites, each with a varied topography and
      distinct land use/land cover, along the length of Lidder River. It was observed
      that water quality deteriorated during the months of June-August that coincides
      with the peak tourist flow and maximal agricultural/horticultural activity. Total
      phosphorus, orthophosphate phosphorus, nitrate nitrogen, and ammoniacal nitrogen
      showed higher concentration in the months of July and August, while the
      concentration of dissolved oxygen decreased in the same period, resulting in
      deterioration in water quality. Moreover, tourism influx in the Lidder Valley
      shows a drastic increase through the years, and particularly, the number of
      tourists visiting the valley has increased in the summer months from June to
      September, which is also responsible for deteriorating the water quality of
      Lidder River. In addition to this, the extensive use of fertilizers and
      pesticides in the agriculture and horticulture lands during the growing season
      (June-August) is also responsible for the deteriorating water quality of Lidder
      River.

PMID- 23001555
TI  - Measurement of biochemical oxygen demand of the leachates.
AB  - Biochemical oxygen demand (BOD) of the leachates originally from the different
      types of landfill sites was studied based on the data measured using the two
      manometric methods. The measurements of BOD using the dilution method were
      carried out to assess the typical physicochemical and biological characteristics
      of the leachates together with some other parameters. The linear regression
      analysis was used to predict rate constants for biochemical reactions and
      ultimate BOD values of the different leachates. The rate of a biochemical
      reaction implicated in microbial biodegradation of pollutants depends on the
      leachate characteristics, mass of contaminant in the leachate, and nature of the
      leachate. Character of leachate samples for BOD analysis of using the different
      methods may differ significantly during the experimental period, resulting in
      different BOD values. This work intends to verify effect of the different
      dilutions for the manometric method tests on the BOD concentrations of the
      leachate samples to contribute to the assessment of reaction rate and microbial
      consumption of oxygen.

PMID- 23001556
TI  - Lisdexamfetamine dimesylate improves processing speed and memory in cognitively
      impaired MS patients: a phase II study.
AB  - Multiple sclerosis (MS) causes cognitive impairment including slowed processing
      speed and problems with learning and memory. Stimulants are attractive candidates
      for improving mental speed but carry risk of addiction and other adverse
      behavioral effects. Lisdexamfetamine dimesylate (LDX) is a D-amphetamine prodrug
      currently approved for attention deficit (hyperactivity) disorder with the
      potential to be better tolerated due to its prolonged clinical effect. This phase
      II placebo-controlled, double-blind study aimed to assess the safety and efficacy
      of LDX in cognitively impaired MS patients. Subjects were patients with
      clinically definite MS, aged 18-56 years, and impaired on either of two primary
      outcomes: the Symbol Digit Modalities Test (SDMT) or the Paced Auditory Serial
      Addition Test (PASAT). Both SDMT and PASAT are measures of cognitive processing
      speed. Of 174 MS patients screened, 63 were randomized to 30 mg of LDX or placebo
      in a 2:1 fashion; the dose was increased as tolerated to 70 mg over 4 weeks and
      then maintained for another 4 weeks. Secondary outcomes were the Brief
      Visuospatial Memory Test Revised (BVMTR), the California Verbal Learning Test 2nd
      edition (CVLT2), both measures of episodic memory, and the Behavioral Rating
      Inventory of Executive Function for adults (BRIEF-A), a self-report measure of
      executive function. Fatigue and depression were also evaluated. There was
      significant improvement in the SDMT score (+4.6 vs. +1.3) and CVLT2 score (+4.7
      vs. -0.9) in the LDX group compared with the placebo group among the 49
      completers. There was no change on the other outcomes. A high proportion of both
      LDX-treated and placebo-treated subjects reported adverse events (73.5 % vs. 68.4
      %). However, there were no serious adverse events noted in the study. These
      preliminary data indicate that LDX has the potential to be an efficacious
      treatment for MS patients with cognitive impairment.

PMID- 23001561
TI  - A novel long-range enhancer regulates postnatal expression of Zeb2: implications
      for Mowat-Wilson syndrome phenotypes.
AB  - The zinc-finger, E-box-binding homeobox-2 (Zeb2) gene encodes a SMAD-interacting
      transcription factor that has diverse roles in development and disease. Mutations
      at the hZeb2 locus cause Mowat-Wilson syndrome (MWS), a genetic disorder that is
      associated with mental retardation and other, case- and sex-dependent clinical
      features. Recent studies have detailed microRNA-mediated control of Zeb2, but
      little is known about the genomic context of this gene or of enhancer sequences
      that may direct its diverse functions. Here, we describe a novel transgenic
      rodent model in which Zeb2 regulatory sequence has been disrupted, resulting in a
      postnatal developmental phenotype that is autosomal dominant. The phenotype
      exhibits a genotype-by-sex interaction and manifests primarily as an acute
      attenuation of postnatal kidney development in males. Other aspects of embryonic
      and neonatal development, including neuronal, are unaffected. The transgene
      insertion site is associated with a 12 kb deletion, 1.2 Mb upstream of Zeb2,
      within a 4.1 Mb gene desert. A conserved sequence, derived from the deleted
      region, enhanced Zeb2 promoter activity in transcription assays. Tissue and
      temporal restriction of this enhancer activity may involve postnatal changes in
      proteins that bind this sequence. A control human/mouse VISTA enhancer (62 kb
      upstream of Zeb2) also up-regulated the Zeb2 promoter, providing evidence of a
      string of conserved distal enhancers. The phenotype arising from deletion of one
      copy of the extreme long-range enhancer indicates a critical role for this
      enhancer at one developmental stage. Haploinsufficiency of Zeb2 in this
      developmental context reflects inheritance of MWS and may underlie some sex
      dependent, non-neural characteristics of this human inherited disorder.

PMID- 23001562
TI  - Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to
      mutations in the CRB1 gene.
AB  - In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of
      autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However,
      there is no clear genotype-phenotype correlation for CRB1 mutations, which
      suggests that other components of the CRB complex may influence the severity of
      retinal disease. Therefore, to understand the physiological role of the Crumbs
      complex proteins, we generated and analysed conditional knockout mice lacking
      CRB2 in the developing retina. Progressive disorganization was detected during
      late retinal development. Progressive thinning of the photoreceptor layer and
      sites of cellular mislocalization was detected throughout the CRB2-deficient
      retina by confocal scanning laser ophthalmoscopy and spectral domain optical
      coherence tomography. Under scotopic conditions using electroretinography, the
      attenuation of the a-wave was relatively stronger than that of the b-wave,
      suggesting progressive degeneration of photoreceptors in adult animals.
      Histological analysis of newborn mice showed abnormal lamination of immature rod
      photoreceptors and disruption of adherens junctions between photoreceptors,
      Muller glia and progenitor cells. The number of late-born progenitor cells, rod
      photoreceptors and Muller glia cells was increased, concomitant with programmed
      cell death of rod photoreceptors. The data suggest an essential role for CRB2 in
      proper lamination of the photoreceptor layer and suppression of proliferation of
      late-born retinal progenitor cells.

PMID- 23001563
TI  - A novel role for doublecortin and doublecortin-like kinase in regulating growth
      cone microtubules.
AB  - Doublecortin (DCX) and doublecortin-like kinase (DCLK), closely related family
      members, are microtubule-associated proteins with overlapping functions in both
      neuronal migration and axonal outgrowth. In growing axons, these proteins appear
      to have their primary functions in the growth cone. Here, we used siRNA to
      deplete these proteins from cultured rat sympathetic neurons. Normally,
      microtubules in the growth cone exhibit a gently curved contour as they extend
      from the base of the cone toward its periphery. However, following depletion of
      DCX and DCLK, microtubules throughout the growth cone become much more curvy,
      with many microtubules exhibiting multiple prominent bends over relatively short
      distances, creating a configuration that we termed wave-like folds. Microtubules
      with these folds appeared as if they were buckling in response to powerful
      forces. Indeed, inhibition of myosin-II, which generates forces on the actin
      cytoskeleton to push microtubules in the growth cone back toward the axonal
      shaft, significantly decreases the frequency of these wave-like folds. In
      addition, in the absence of DCX and DCLK, the depth of microtubule invasion into
      filopodia is reduced compared with controls, and at a functional level, growth
      cone responses to substrate guidance cues are altered. Conversely, overexpression
      of DCX results in microtubules that are straighter than usual, suggesting that
      higher levels of these proteins can enable an even greater resistance to folding.
      These findings support a role for DCX and DCLK in enabling microtubules to
      overcome retrograde actin-based forces, thereby facilitating the ability of the
      growth cone to carry out its crucial path-finding functions.

PMID- 23001564
TI  - Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere
      homeostasis in humans.
AB  - Leukocyte telomere length (LTL) is associated with a number of common age-related
      diseases and is a heritable trait. Previous genome-wide association studies
      (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1)
      that are associated with the inter-individual LTL variation. We performed a meta
      analysis of 9190 individuals from six independent GWAS and validated our findings
      in 2226 individuals from four additional studies. We confirmed previously
      reported associations with OBFC1 (rs9419958 P = 9.1 * 10(-11)) and with the
      telomerase RNA component TERC (rs1317082, P = 1.1 * 10(-8)). We also identified
      two novel genomic regions associated with LTL variation that map near a conserved
      telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 * 10(-8)) on
      chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 * 10(
      8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL
      and lower expression of CTC1. Our findings are consistent with the recent
      observations that point mutations in CTC1 cause short telomeres in both
      Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our
      results provide novel insights into the genetic architecture of inter-individual
      LTL variation in the general population.

PMID- 23001566
TI  - An inherited TUBB2B mutation alters a kinesin-binding site and causes
      polymicrogyria, CFEOM and axon dysinnervation.
AB  - Microtubules are essential components of axon guidance machinery. Among beta
      tubulin mutations, only those in TUBB3 have been shown to cause primary errors in
      axon guidance. All identified mutations in TUBB2B result in polymicrogyria, but
      it remains unclear whether TUBB2B mutations can cause axon dysinnervation as a
      primary phenotype. We have identified a novel inherited heterozygous missense
      mutation in TUBB2B that results in an E421K amino acid substitution in a family
      who segregates congenital fibrosis of the extraocular muscles (CFEOM) with
      polymicrogyria. Diffusion tensor imaging of brains of affected family members
      reveals aberrations in the trajectories of commissural projection neurons,
      implying a paucity of homotopic connections. These observations led us to ask
      whether axon dysinnervation is a primary phenotype, and why the E421K, but not
      other, TUBB2B substitutions cause CFEOM. Expression of exogenous Tubb2b-E421K in
      developing callosal projection neurons is sufficient to perturb homotopic
      connectivity, without affecting neuronal production or migration. Using in vitro
      biochemical assays and yeast genetics, we find that TUBB2B-E421K alphabeta
      heterodimers are incorporated into the microtubule network where they alter
      microtubule dynamics and can reduce kinesin localization. These data provide
      evidence that TUBB2B mutations can cause primary axon dysinnervation.
      Interestingly, by incorporating into microtubules and altering their dynamic
      properties, the E421K substitution behaves differently than previously identified
      TUBB2B substitutions, providing mechanistic insight into the divergence between
      resulting phenotypes. Together with previous studies, these findings highlight
      that beta-tubulin isotypes function in both conserved and divergent ways to
      support proper human nervous system development.

PMID- 23001565
TI  - A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity
      and increased susceptibility to proteostatic insult.
AB  - The autosomal dominant spinocerebellar ataxias (SCAs) are a genetically
      heterogeneous group of disorders exhibiting cerebellar atrophy and Purkinje cell
      degeneration whose subtypes arise from 31 distinct genetic loci. Our group
      previously published the locus for SCA26 on chromosome 19p13.3. In this study, we
      performed targeted deep sequencing of the critical interval in order to identify
      candidate causative variants in individuals from the SCA26 family. We identified
      a single variant that co-segregates with the disease phenotype that produces a
      single amino acid substitution in eukaryotic elongation factor 2. This
      substitution, P596H, sits in a domain critical for maintaining reading frame
      during translation. The yeast equivalent, P580H EF2, demonstrated impaired
      translocation, detected as an increased rate of -1 programmed ribosomal
      frameshift read-through in a dual-luciferase assay for observing translational
      recoding. This substitution also results in a greater susceptibility to
      proteostatic disruption, as evidenced by a more robust activation of a reporter
      gene driven by unfolded protein response activation upon challenge with
      dithiothreitol or heat shock in our yeast model system. Our results present a
      compelling candidate mutation and mechanism for the pathogenesis of SCA26 and
      further support the role of proteostatic disruption in neurodegenerative
      diseases.

PMID- 23001568
TI  - A fully humanized transgenic mouse model of Huntington disease.
AB  - Silencing the mutant huntingtin gene (muHTT) is a direct and simple therapeutic
      strategy for the treatment of Huntington disease (HD) in principle. However,
      targeting the HD mutation presents challenges because it is an expansion of a
      common genetic element (a CAG tract) that is found throughout the genome.
      Moreover, the HTT protein is important for neuronal health throughout life, and
      silencing strategies that also reduce the wild-type HTT allele may not be well
      tolerated during the long-term treatment of HD. Several HTT silencing strategies
      are in development that target genetic sites in HTT that are outside of the CAG
      expansion, including HD mutation-linked single-nucleotide polymorphisms and the
      HTT promoter. Preclinical testing of these genetic therapies has required the
      development of a new mouse model of HD that carries these human-specific genetic
      targets. To generate a fully humanized mouse model of HD, we have cross-bred
      BACHD and YAC18 on the Hdh(-/-) background. The resulting line, Hu97/18, is the
      first murine model of HD that fully genetically recapitulates human HD having two
      human HTT genes, no mouse Hdh genes and heterozygosity of the HD mutation. We
      find that Hu97/18 mice display many of the behavioral changes associated with HD
      including motor, psychiatric and cognitive deficits, as well as canonical
      neuropathological abnormalities. This mouse line will be useful for gaining
      additional insights into the disease mechanisms of HD as well as for testing
      genetic therapies targeting human HTT.

PMID- 23001567
TI  - Polycystin-1 regulates the stability and ubiquitination of transcription factor
      Jade-1.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) and von Hippel-Lindau (VHL)
      disease lead to large kidney cysts that share pathogenetic features. The
      polycystin-1 (PC1) and pVHL proteins may therefore participate in the same key
      signaling pathways. Jade-1 is a pro-apoptotic and growth suppressive ubiquitin
      ligase for beta-catenin and transcriptional coactivator associated with histone
      acetyltransferase activity that is stabilized by pVHL in a manner that correlates
      with risk of VHL renal disease. Thus, a relationship between Jade-1 and PC1 was
      sought. Full-length PC1 bound, stabilized and colocalized with Jade-1 and
      inhibited Jade-1 ubiquitination. In contrast, the cytoplasmic tail or the
      naturally occurring C-terminal fragment of PC1 (PC1-CTF) promoted Jade-1
      ubiquitination and degradation, suggesting a dominant-negative mechanism. ADPKD
      associated PC1 mutants failed to regulate Jade-1, indicating a potential disease
      link. Jade-1 ubiquitination was mediated by Siah-1, an E3 ligase that binds PC1.
      By controlling Jade-1 abundance, PC1 and the PC1-CTF differentially regulate Jade
      1-mediated transcriptional activity. A key target of PC1, the cyclin-dependent
      kinase inhibitor p21, is also up-regulated by Jade-1. Through Jade-1, PC1 and PC1
      cleaved forms may exert fine control of beta-catenin and canonical Wnt signaling,
      a critical pathway in cystic renal disease. Thus, Jade-1 is a transcription
      factor and ubiquitin ligase whose activity is regulated by PC1 in a manner that
      is physiologic and may correlate with disease. Jade-1 may be an important
      therapeutic target in renal cystogenesis.

PMID- 23001570
TI  - Efficacy of low-level laser therapy in the management of orthodontic pain: a
      systematic review and meta-analysis.
AB  - This review aimed to identify the efficacy of low-level laser therapy (LLLT) in
      the management of orthodontic pain. This systematic review and meta-analysis was
      carried out in accordance with Cochrane Handbook and the PRISMA statement. An
      extensive literature search for RCTs, quasi-RCTs, and CCTs was performed through
      CENTRAL, PubMed, Embase, Medline, CNKI, and CBM up to October 2011. Risk of bias
      assessment was performed via referring to the Cochrane tool for risk of bias
      assessment. Meta-analysis was implemented using Review Manager 5.1. As a result,
      four RCTs, two quasi-RCTs, and two CCTs were selected from 152 relevant studies,
      including 641 patients from six countries. The meta-analysis demonstrated that
      24% risk of incidence of pain was reduced by LLLT (RR = 0.76, 95% CI range 0.63
      0.92, P = 0.006). In addition, compared to the control group, LLLT brought
      forward "the most painful day" (MD = -0.42, 95% CI range -0.74- -0.10, P =
      0.009). Furthermore, the LLLT group also implied a trend of earlier end of pain
      compared with the control group (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18)
      and the pseudo-laser group (MD = -1.04, 95% CI range -4.22-2.15, P = 0.52).
      However, because of the methodological shortcomings and risk of bias of included
      trials, LLLT was proved with limited evidence in delaying pain onset and reducing
      pain intensity. In the future, larger and better-designed RCTs will be required
      to provide clearer recommendations.

PMID- 23001571
TI  - Effectiveness of the Transoral Endoscopic Vertical Gastroplasty (TOGa(r)): a good
      balance between weight loss and complications, if compared with gastric bypass
      and biliopancreatic diversion.
AB  - BACKGROUND: The effectiveness of restrictive procedures has been inferior to that
      of malabsorbitive ones. Recent variants of restrictive procedures, i.e., gastric
      banding and sleeve gastrectomy, confirm the strive for more efficacious solutions
      with less complications. We investigated the balance between effectiveness and
      complications for a new restrictive procedure, a Transoral Endoscopic Vertical
      Gastroplasty (TOGa(r)) METHODS: Seventy-nine morbidly obese patients were
      submitted to one out of three surgical procedures: TOGa(r) (29 patients),
      laparoscopic gastric bypass (LRYGBP; 20 patients), and biliopancreatic diversion
      (BPD; 30 patients). Mean BMI were 41.7 (35.4-46.6), 44.8 (36.4-54), and 47.5 (41
      60.3), respectively. All the patients reached a 2-year follow-up. RESULTS: In
      TOGa(r) group BMI, respectively at 12 and 24 months, was 34.5 and 35.5, with 44
      and 48.3% of patients with BMI lower than 35. In LRYGBP group, BMI was 30.7 and
      29.2 kg/m(2), with 80 and 85% of patients with BMI < 35. In BPD group, BMI was 30
      and 29.6 kg/m(2), with 100 and 93.3% of patients with BMI < 35. In TOGa(r) group,
      59% of patients with an initial BMI < 45 reached a BMI < 35, in comparison to 48%
      recorded in the whole group and to 14.3% in patients with initial BMI >= 45.
      CONCLUSIONS: In selected patients, TOGa(r), was associated with good results
      after two years in terms of weight loss, even in comparison with LRYGBP and BPD.
      Minimal trauma, absence of complications, and short hospital stay justify this
      procedure for patients with low BMI.

PMID- 23001572
TI  - Indications and short-term outcomes of revisional surgery after failed or
      complicated sleeve gastrectomy.
AB  - BACKGROUND: Sleeve gastrectomy (SG) is an upcoming primary treatment modality for
      morbid obesity. The aim of this study was to report the indications for and the
      outcomes of revisional surgery after SG. METHODS: Four hundred sixteen
      individuals underwent a SG between August 2006 and July 2010 with a minimum
      follow-up of 12 months. The patients that needed revision were identified from
      our prospective registry. Patients were subdivided in a first group undergoing
      revision as part of a two-step procedure, a second group with failure of a
      secondary SG, and a third group with failure of a primary SG. RESULTS: Twenty
      three patients (5.5%) had an unplanned revision. Fourteen (3.4%) had a two-step
      procedure because of super obesity. A significant additional weight loss was
      achieved after revision; no complications occurred in this group. Five patients
      with failure of a secondary SG had no significant additional weight loss after
      revision. Reflux disease was cured. Eighteen patients in the third group showed
      significant additional weight loss and remission of diabetes and hypertension.
      Both reflux disease and dysphagia did not heal in all affected patients after
      revision. The early complication rate in the whole cohort was 23.4%; staple line
      leakage was 5.4%, and bleeding was 8.1%. Revision-related mortality was 0%.
      CONCLUSION: In a large series of sleeve gastrectomies, the unplanned revision
      rate was 5.5%. Revision of a sleeve gastrectomy is feasible in patients that do
      not achieve sufficient weight loss and in those patients developing complications
      after the initial sleeve gastrectomy.

PMID- 23001573
TI  - Repeat sleeve gastrectomy compared with primary sleeve gastrectomy: a single
      center, matched case study.
AB  - Longitudinal sleeve gastrectomy (LSG) has been validated for the treatment of
      morbid obesity. However, treatment failures can appear several months after SG.
      Additional malabsorptive surgery is generally recommended in such cases. The
      objective of the present study was to evaluate the outcomes of repeat SG (re-SG)
      relative to first-line SG. This was a retrospective study included 15 patients
      underwent re-SG after failure of first-line SG (i.e. University Hospital, France;
      Public Practice). These patients were matched (for age, gender, body mass index
      and comorbidities) 1:2 with 30 patients having undergone first-line SG. The
      efficacy criteria comprised intra-operative data and postoperative data. The
      overall study population comprised 45 patients. The re-SG and first-line SG
      groups did not differ significantly in terms of median age (p = NS). The median
      BMI was similar in the two groups (43 kg/m(2) vs. 42.3 kg/m(2), p = NS). The two
      groups were similar in terms of the prevalence of comorbidities. The mean
      operating time was longer in the re-SG group (116 vs. 86 min; p <= 0.01). The
      postoperative complication rate was twice as high in the re-SG group (p = 0.31).
      Two patients in the re-SG group developed a gastric fistula (p = 0.25) and one of
      the latter died. At 12 months, the Excess Weight Loss was 66% (re-SG group) and
      77% (first-line SG group) (p = 0.05). Re-SG is feasible but appears to be
      associated with a greater risk of complications. Nevertheless, re-SG can produce
      results (in terms of weight loss), equivalent to those obtained after first-line
      SG.

PMID- 23001574
TI  - ESPR Uroradiology Task Force and ESUR Paediatric Working Group--Imaging
      recommendations in paediatric uroradiology, part V: childhood cystic kidney
      disease, childhood renal transplantation and contrast-enhanced ultrasonography in
      children.
AB  - The ESPR Uroradiology Task Force and the ESUR Paediatric Working Group present
      two new recommendations on imaging in childhood cystic kidney disease and in
      childhood renal transplantation, and address the presently restricted
      availability of contrast-enhanced (ce) US in children. New insights into the
      genetics require an updated classification of paediatric cystic kidney disease
      along with a new concept of diagnostic imaging. Characteristic imaging features
      are key to the new classification. Available recommendations for imaging renal
      transplantation in children are not satisfactory. The following consensus-based
      algorithm proposes a more effective and more uniform imaging concept, reducing
      invasiveness, enhancing diagnostic accuracy, and facilitating future multicentre
      studies and meta-analysis. At present, ce-US in children can only be performed
      off-license, since the only approved US contrast agent (CA) for children has been
      taken off the market. Nevertheless, paediatric ce-US is practiced at multiple
      places using Sonovue (Bracco, Milan, Italy), a generally available agent in
      Europe. From a medical and scientific perspective, paediatric ce-US should be
      promoted, and efforts are undertaken to collect data on paediatric US-CA
      applications. Routine paediatric imaging depends on local expertise and
      availability of equipment. The imaging recommendations and supportive data are
      intended to ease the physicians' difficult task of dealing with the specific
      diagnostic demands of paediatric paediatric cystic kidney disease and
      transplantation.

PMID- 23001575
TI  - Can the beneficial effects of methionine restriction in rats be explained in part
      by decreased methylglyoxal generation resulting from suppressed carbohydrate
      metabolism?
AB  - The mechanisms by which dietary restriction of the amino acid methionine exerts
      beneficial effects on oxidative damage towards rat liver mitochondria are
      discussed. It is suggested that methionine restriction decreases amino acid
      utilization in protein synthesis which, by decreasing synthesis of non-essential
      amino acids from carbohydrate precursors, also decreases formation of the highly
      deleterious glycolytic by-product methylglyoxal, a well-recognised source of age
      related damage including formation of reactive oxygen species, mitochondrial
      dysfunction and proteotoxicity. Additionally, decreased protein synthesis will
      lower the error-protein load which the protein quality system (proteasomal and
      autophagic) must deal with to maintain proteostasis.

PMID- 23001569
TI  - Gene-centric meta-analyses of 108 912 individuals confirm known body mass index
      loci and reveal three novel signals.
AB  - Recent genetic association studies have made progress in uncovering components of
      the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad
      Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320
      single nucleotide polymorphisms (SNPs) across ~2100 metabolic and cardiovascular
      related loci to genotype up to 108 912 individuals of European ancestry (EA),
      African-Americans, Hispanics and East Asians, from 46 studies, to provide
      additional insight into SNPs underpinning BMI. We used a five-phase study design:
      Phase I focused on meta-analysis of EA studies providing individual level
      genotype data; Phase II performed a replication of cohorts providing summary
      level EA data; Phase III meta-analyzed results from the first two phases;
      associated SNPs from Phase III were used for replication in Phase IV; finally in
      Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was
      performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI
      associations in loci translocase of outer mitochondrial membrane 40 homolog
      (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P
      = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2,
      rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2
      [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P =
      1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for
      BMI association represented on the IBC array, eight were replicated, with the
      remaining two showing nominal significance. Conditional analyses revealed two
      independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R)
      regions. Of the 11 array-wide significant SNPs, three are associated with gene
      expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B
      adaptor protein 1 (SH2B1) notably being associated with the expression of
      multiple genes in cis. These multi-ethnic meta-analyses expand our knowledge of
      BMI genetics.

PMID- 23001576
TI  - EBV primary infection in childhood and its relation to B-cell lymphoma
      development: a mini-review from a developing region.
AB  - In most underdeveloped countries, the initial contact with Epstein Barr virus
      (EBV) usually happens in the first decade of life and results in an asymptomatic
      infection, whereas in developed areas, primary infection in adolescence or
      adulthood is accompanied by infectious mononucleosis in 50% cases. Although it is
      generally a harmless passenger, in some individuals, it is associated with B-cell
      lymphoma. In Argentina, EBV primary infection shows the classical pattern
      observed in developing populations, given that nearly 70% of patients are
      seropositive by the age of 2 years. However, EBV association with pediatric
      Hodgkin and Burkitt lymphoma resembles that observed in developed regions.
      Concerning diffuse large B-cell lymphoma, our series demonstrated higher EBV
      association than other adult ones from either developed or underdeveloped
      countries. Interestingly, the early EBV primary infection observed,
      characteristic of an underdeveloped population, together with the statistically
      significant EBV association with patients <= 10 years old demonstrated in all
      types of lymphoma studied, suggest a relationship between low age of EBV
      seroconversion and B-cell lymphoma development risk.

PMID- 23001577
TI  - Terminalia arjuna improves cardiovascular autonomic neuropathy in streptozotocin
      induced diabetic rats.
AB  - The present study was designed to examine the therapeutic potential of Terminalia
      arjuna bark extract in improving cardiovascular autonomic neuropathy in
      Streptozotocin (STZ)-induced diabetic Wistar Albino rats. The baroreflex was
      evaluated by measuring the changes in heart rate with changes in arterial blood
      pressure induced by bolus injections of phenylephrine (vasoconstrictor) and
      sodium nitroprusside (vasodilator). T. arjuna bark extract, Rosuvastatin and
      Insulin were tested/administered therapeutically in rat model of uncontrolled
      diabetes. After 8 weeks of STZ administration, the reflex bradycardia and
      tachycardia response to hypertension and hypotension, respectively, were impaired
      in the diabetic group. The reflex bradycardia improved significantly after 1
      month treatment of T. arjuna while the reflex tachycardia could not improve. The
      decreased body weight, heart rate, blood pressure and raised blood sugar in
      diabetic rats were not improved by T. arjuna therapy. Rosuvastatin treatment
      exerted similar effects while Insulin improved all the parameters. Further T.
      arjuna, Rosuvastatin and Insulin significantly reduced oxidative stress and
      inflammatory cytokine levels in diabetic rats. Results suggest that T. arjuna
      bark extract improves the altered baroreflex sensitivity in diabetic rats
      possibly through maintaining endogenous antioxidant enzyme activities and
      decreasing cytokine levels.

PMID- 23001578
TI  - Characteristics of vascular supply to uterine leiomyoma: an analysis of digital
      subtraction angiography imaging in 518 cases.
AB  - OBJECTIVES: To investigate the characteristics of the vascular supply to uterine
      leiomyomas based on digital subtraction angiography. METHODS: The feeding artery,
      vascularity of uterine leiomyoma and visualisation of the ovarian vessel network
      were studied in 518 patients undergoing uterine artery embolisation (UAE). Mean
      patient age was 38.97 +/- 6.09 years (range, 22-54 years). The types of vascular
      supply were analysed by the vascular supply to the leimyoma and grades of
      vascularity by the degree of enhancement of the leimyoma compared with the
      myometrium. RESULTS: The blood supply of leiomyomas could not be classified in
      3.28 % of patients. Blood was supplied solely by the uterine artery in 88.61 % of
      leiomyomas, 8.11 % of leiomyomas were partially fed by an ovarian artery, and
      0.39 % by it exclusively. Leiomyoma blood supply was classified as unilateral
      predominant, bilateral balanced, single unilateral uterine artery and single
      ovarian artery in 36.48, 49.23, 10.62 and 0.39 % of cases respectively. Leiomyoma
      vascularity was classified as extremely hypervascular (8.69 %), hypervascular
      (46.14 %), isovascular (33.39 %) and hypovascular (11.78 %). CONCLUSIONS: Uterine
      leiomyomas supplied by both uterine arteries and with rich blood flow were seen
      in approximately 50 % of patients. However, close attention also should be given
      to the collateral circulation during UAE.

PMID- 23001579
TI  - Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver
      metastases: functional and morphological evaluation.
AB  - OBJECTIVE: To evaluate morphological and perfusion changes in liver metastases of
      neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial
      embolisation with bead block (TAE) or trans-arterial chemoembolisation with
      doxorubicin-eluting beads (DEB-TACE). METHODS: In this retrospective study, seven
      patients underwent TAE, and ten underwent DEB-TACE using beads of the same size.
      At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a
      destruction-replenishment study using CEUS was performed with a microbubble
      enhancing contrast material on a reference tumour. Relative blood flow (rBF) and
      relative blood volume (rBV) were obtained from the ratio of values obtained in
      the tumour and in adjacent liver parenchyma. Morphological parameters such as the
      tumour's major diameter and the viable tumour's major diameter were also
      measured. A parameter combining functional and morphological data, the tumour
      vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher's test
      were used to compare treatment groups. RESULTS: At 3 months rBF, rBV and TVI were
      significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with
      doxorubicin. No difference in morphological parameters was found throughout the
      follow-up. CONCLUSIONS: One parameter, TVI, could evaluate the morphological and
      functional response to treatments.

PMID- 23001580
TI  - Kinematic shoulder MRI: the diagnostic value in acute shoulder dislocations.
AB  - OBJECTIVES: To determine whether positioning of the arm in adduction and internal
      rotation would improve the confidence in the diagnosis of Bankart lesions in
      first time shoulder dislocators. METHODS: Eleven patients were imaged on an open
      bore MRI within 1-6 days of traumatic shoulder dislocation with the arm adducted
      and internally rotated, and subsequently the patients were reimaged with the arm
      adduced and externally rotated. Two blinded musculoskeletal radiologists
      determined the confidence of diagnosing labral tears in each of the two
      positions. RESULTS: An anterior-inferior labral tear was diagnosed in 11/11
      patients in internal rotation and in 6/11 patients in external rotation. The
      average confidence was 2.8 in internal rotation and 1.5 in external rotation (on
      a scale of 0-3). Using a Wilcoxon signed rank test, the certainty of the
      diagnosis was determined to be significantly higher with the arm in internal
      rotation (P = 0.016). CONCLUSIONS: MRI performed with the arm in internal
      rotation for patients with acute first time anterior shoulder dislocation
      increases the certainty of the diagnosis of anterior-inferior labral tears.

PMID- 23001581
TI  - Increased risk of depressive disorder following diagnosis with bladder pain
      syndrome/interstitial cystitis.
AB  - AIM: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain
      syndrome of unknown etiology that primarily affects women. Using a longitudinal
      follow-up design, this study aimed to examine the risk of depressive disorder
      (DD) among women with BPS/IC compared to the general population during a 1-year
      period following their diagnosis. METHOD: This study used data from the Taiwan
      "Longitudinal Health Insurance Database." A total of 832 patients with BPS/IC
      were included in the study group and 4,160 matched non-BPS/IC enrollees were
      included as the comparison group. Each patient (n = 4,992) was individually
      tracked for a 1-year period to identify those who subsequently received a
      diagnosis of DD. Cox proportional hazards regressions (stratified by age group
      and the index year) were used to estimate the risk of subsequent DD following a
      diagnosis of BPS/IC. RESULTS: We found that during the 1-year follow-up, the
      incidence rate of DD was 4.69 (95% CI: 3.38-6.34) per 100 person-years in
      patients with BPS/IC and 0.94 (95% CI: 0.68-1.27) per 100 person-years in
      comparison patients. The hazard ratio (HR) of DD during the 1-year follow-up
      period for patients with BPS/IC was 5.06 (95% CI: 3.21-7.96, P < 0.001) that of
      comparison patients after adjusting for patient monthly income, geographic
      location, and urbanization level. The adjusted HR for DD associated with BPS/IC
      was 10.33 for patients aged between 40 and 49 (95% CI: 3.68-29.04). CONCLUSION:
      Our study demonstrated that there is an increased risk for being diagnosed with
      DD during the first year subsequent to being diagnosed with IC/PBS.

PMID- 23001582
TI  - Replacement levels of elephant grass by moist pineapple by-product silage in
      diets of Santa Ines crossbred sheep: performance and digestibility.
AB  - The present study evaluated the effect of replacing elephant grass (EG) with
      moist pineapple by-product silage (PS) on the apparent digestibility, consumption
      of digestible nutrients and performance of 25 castrated male lambs Santa Ines
      crossbreds. The lambs had an initial body weight of 20.2 +/- 3.5 kg and were
      housed in individual pens in a completely randomised design with five treatments
      (replacement of EG by PS at five proportions of 0, 25, 50, 75 and 100 %) and five
      replicates during 74 days. There was no significant effect of PS replacement
      proportions on the intake of dry matter (DM), organic matter (OM), total
      carbohydrates (TC), non-fibrous carbohydrates or total digestible nutrients
      (TDN). The consumption of crude protein (CP) decreased linearly with the
      inclusion of PS in the diets. The digestibility of DM, OM and TCs as well as
      levels of TDN increased linearly with the addition of PS. The use of PS in the
      diets had no significant effect on the digestibility of CP and neutral detergent
      fibre corrected for ashes and protein (NDFom(n)). These results demonstrated that
      there was no difference in the performance of animals fed diets with or without
      PS.

PMID- 23001583
TI  - Complex invasion pattern of the cerebral cortex bymicroglial cells during
      development of the mouse embryo.
AB  - Microglia are the immune cells of the central nervous system. They are suspected
      to play important roles in adult synaptogenesis and in the development of the
      neuronal network. Microglial cells originate from progenitors in the yolk sac.
      Although it was suggested that they invade the cortex at early developmental
      stages in the embryo, their invasion pattern remains largely unknown. To address
      this issue we analyzed the pattern of cortical invasion by microglial cells in
      mouse embryos at the onset of neuronal cell migration using in vivo
      immunohistochemistry and ex vivo time-lapse analysis of microglial cells.
      Microglial cells begin to invade the cortex at 11.5 days of embryonic age
      (E11.5). They first accumulate at the pial surface and within the lateral
      ventricles, after which they spread throughout the cortical wall, avoiding the
      cortical plate region in later embryonic ages. The invasion of the cortical
      parenchyma occurs in different phases. First, there is a gradual increase of
      microglial cells between E10.5 and E14.5. From E14.5 to E15.5 there is a rapid
      phase with a massive increase in microglia, followed by a slow phase again from
      E15.5 until E17.5. At early stages, many peripheral microglia are actively
      proliferating before entering the parenchyma. Remarkably, activated microglia
      accumulate in the choroid plexus primordium, where they are in the proximity of
      dying cells. Time-lapse analysis shows that embryonic microglia are highly
      dynamic cells.

PMID- 23001584
TI  - Inflammatory breast cancer in north Africa: comparison of clinical and molecular
      epidemiologic characteristics of patients from Egypt, Tunisia, and Morocco.
AB  - Understanding molecular characteristics that distinguish inflammatory breast
      cancer (IBC) from non-IBC is crucial for elucidating breast cancer etiology and
      management. We included 3 sets of patients from Egypt (48 IBC and 64 non-IBC),
      Tunisia (24 IBC and 40 non-IBC), and Morocco (42 IBC and 41 non-IBC). Egyptian
      IBC patients had the highest combined erythema, edema, peau d'orange, and
      metastasis among the 3 IBC groups. Egyptian IBC tumors had the highest RhoC
      expression than Tunisians and Moroccan IBCs (87% vs. 50%, vs. 38.1, for the 3
      countries, respectively). Tumor emboli were more frequent in Egyptian IBC than
      non-IBC (Mean +/- SD: 14.1 +/- 14.0 vs. 7.0 +/- 12.9, respectively) (P < 0.001)
      and Tunisians (Mean +/- SD: 3.4 +/- 2.5 vs. 1.9 +/- 2.0, respectively) (P <
      0.01). There was no difference of emboli in Moroccan tumors (1.7 +/- 1.2 vs. 1.8
      +/- 1.2 for IBC and non-IBC, respectively (P=0.66). This study illustrates that
      RhoC overexpression and tumor emboli are more frequent in IBC relative to non-IBC
      from Egypt and Tunisia. Tumors of Moroccans were significantly different from
      Egyptian and Tunisian tumors for RhoC expression and emboli. Future studies
      should focus on relating epidemiologic factors and clinical pictures to molecular
      features of IBC in these and other populations.

PMID- 23001585
TI  - Comparison of visual and refractive results of Toric Implantable Collamer Lens
      with bioptics for myopic astigmatism.
AB  - PURPOSE: To compare visual and refractive results of Toric Implantable Collamer
      Lens (TICL) and bioptics (ICL plus excimer corneal surgery) to treat myopic
      astigmatism. METHODS: Eighty-one eyes underwent TICL implantation and 83 eyes
      were treated with bioptics (corneal ablation was performed between 1.5 and 6
      months after ICL implantation). Uncorrected distance visual acuity (UDVA),
      corrected distance visual acuity (CDVA), refraction, adverse events, safety, and
      efficacy were evaluated 12 months postoperatively. RESULTS: At 12 months
      postoperatively, the mean spherical equivalent was -0.15 +/- 0.36 diopters (D) in
      the TICL group and -0.08 +/- 0.26 D in the bioptics group (p = 0.099). Sixty-six
      (81.5 %) and 78 (94.0 %) eyes were within +/-0.50 D for TICL and bioptics groups,
      respectively. The mean Snellen UDVA was not statistically different between both
      procedures (p = 0.909); 53 (65.4 %) and 54 (65.1 %) eyes achieved at least 20/25
      or better in TICL and bioptics groups, respectively. No eye had lost more than
      two lines of CDVA, and 32.1 % of eyes (26/81) in the TICL group and 57.8 % of
      eyes (48/83) in the bioptics group had better postoperative UDVA than
      preoperative CDVA (p < 0.001). Safety was not statistically different between
      groups (p = 0.464) while efficacy was significantly higher in the bioptics group
      (p = 0.000). Two eyes with a TICL were treated to correct TICL decentration.
      CONCLUSIONS: Bioptics showed slightly better outcomes in some clinical measures
      such as uncorrected visual acuity, efficacy, and refractive predictability. TICL
      implantation shows reliable results similar to bioptics. A single procedure with
      TICL implantation might be preferred, eliminating the inherent risks of laser
      treatments and the risks of a second surgical procedure.

PMID- 23001586
TI  - Swept source optical coherence tomography measurement of the iris-trabecular
      contact (ITC) index: a new parameter for angle closure.
AB  - PURPOSE: To evaluate the inter- and intra-observer agreement of measurement of
      the iris-trabecular contact (ITC) index, a measure of the degree of angle
      closure, using swept source optical coherence tomography (SSOCT, CASIA SS-1000,
      Tomey Corporation, Nagoya, Japan). METHODS: One randomly selected eye of 60
      subjects was imaged under dark room conditions. The SSOCT 3-dimensional angle
      scan simultaneously obtains 128 radial scans of the anterior chamber for the
      entire circumference of the angle. Post-imaging analysis estimated the ITC index
      using in-built software. For intra-observer agreement for image grading, one
      examiner performed the grading twice in a masked fashion and random order after a
      1-week interval. A second examiner graded images to assess inter-observer
      agreement for image grading. For intra-observer agreement for image acquisition,
      a single operator imaged patients twice. For inter-observer agreement for image
      acquisition, a single observer graded two sets of images acquired by two
      different operators on the same patient. Bland-Altman plots and 95 % limits of
      agreement (LOA) were reported. RESULTS: Study subjects were predominantly Chinese
      (54/60, 90 %) and female (42/60, 70 %), with a mean age of 65.5 years. The median
      ITC index for eyes with open angles (31/60) and closed angles was 20 % (95 %
      confidence interval [CI] - 13.6, 27.8) and 49 % (95%CI - 35.5, 69.2)
      respectively. The mean difference (95 % LOA) for intra-observer agreement for
      image grading and image acquisition were -0.8 % (-8.2, 6.5) and 0.6 % (-10.9,
      9.7); corresponding inter- observer agreement were 0.1 % (-10, 10.1) and -0.3 % (
      11.1, 10.5) respectively. CONCLUSIONS: The inter- and intra-observer agreement of
      the ITC index, as a measure of extent of angle closure using SSOCT, was good.

PMID- 23001587
TI  - Population pharmacokinetic/pharmacodynamic modelling of the anti-TNF-alpha
      polyclonal fragment antibody AZD9773 in patients with severe sepsis.
AB  - AZD9773 is an ovine-derived, polyclonal, anti-tumour necrosis factor-alpha (TNF
      alpha) antibody fragment. Using data from an AZD9773 Phase IIa study in patients
      with severe sepsis (clinicaltrials.gov: NCT00615017), a population
      pharmacokinetic/pharmacodynamic (PK/PD) model was developed. The model assessed
      the influence of various covariates on the PK of AZD9773 and the relationship
      between AZD9773 exposure and serological TNF-alpha concentration. A linear two
      compartment model was used to describe AZD9773 concentration-time data. A
      stepwise covariate analysis was performed on the PK parameters. Subsequently, the
      serological TNF-alpha concentrations and drug effect were captured using an
      indirect response model, with a variable production rate of TNF-alpha described
      by a quadratic function. Creatinine clearance (CrCL) was the only covariate with
      a significant effect on the PK of AZD9773. A typical patient's drug clearance
      varied with CrCL; the relationship was non-linear. Diagnostic analysis of the
      PK/PD model showed that the fit was good, both across cohorts and in AZD9773
      treated versus placebo patients. Serological TNF-alpha concentrations and the
      reduction of measurable serum TNF-alpha by AZD9773 were well characterized across
      all the cohorts evaluated in the Phase IIa study. This population PK/PD model was
      subsequently used to simulate alternative dosing options for a Phase IIb study
      (clinicaltrials.gov: NCT01145560).

PMID- 23001588
TI  - Longitudinal FEV1 dose-response model for inhaled PF-00610355 and salmeterol in
      patients with chronic obstructive pulmonary disease.
AB  - The objective of this work was to characterize the dose-response relationship
      between two inhaled long-acting beta agonists (PF-00610355 and salmeterol) and
      the forced expiratory volume in one second (FEV1) in order to inform dosing
      recommendations for future clinical trials in patients with chronic obstructive
      pulmonary disease (COPD). This meta-analysis of four studies included 8,513 FEV1
      measurements from 690 patients with moderate COPD. A longitudinal kinetic
      pharmacodynamic (K-PD) model was developed and adequately described changes in
      FEV1 measurements over time, including circadian patterns within a day, as well
      as changes in FEV1 measurements elicited from administration of PF-00610355 or
      salmeterol. The fine-particle dose, the amount of drug present in particles small
      enough for lung delivery, was used as the exposure measure for PF-00610355.
      Greater reversibility following administration of a short-acting beta agonist
      during run-in was associated with increased FEV1 response to long-acting beta
      agonists (through an increased maximal response, E(max)). Simulations were
      conducted to better understand the response to PF-00610355 relative to placebo
      and salmeterol. The results of the simulations show that once daily fine-particle
      doses of 28.1 MUg versus placebo have a moderate probability of providing an
      average improvement above 100 mL at trough. The 50 MUg fine-particle dose, on the
      other hand, has a greater than 0.78 probability of achieving a 120 mL improvement
      versus placebo at trough. From an efficacy perspective and assuming a fine
      particle fraction of 25 % for the Phase 3 formulation; 100 and 200 MUg once daily
      nominal doses would be of interest to investigate in future Phase 3 trials.

PMID- 23001589
TI  - Intestinal absorption of amino acids in the Pacific bluefin tuna (Thunnus
      orientalis): in vitro lysine-arginine interaction using the everted intestine
      system.
AB  - The interaction between lysine (Lys) and arginine (Arg) in the proximal
      intestinal region of Pacific bluefin tuna (Thunnus orientalis) was evaluated
      using the everted intestine method. This in vitro intestinal system has been
      shown to be an effective tool for studying the nutrient absorption without the
      need to handle the tuna fish in marine cages as needed for digestibility and
      amino acid (AA) absorption. We used a factorial design with two sets of
      variables: low and high Lys concentration (10 and 75 mM) and four different Arg
      concentrations (3, 10, 20, and 30 mM). Both amino acids were dissolved in marine
      Ringer solution with a basal amino acidic composition consisting of a tryptone
      solution (9 mg mL(-1)). No interaction was observed between the absorption of Lys
      and Arg during the first 10 min of the experiment when low concentration of Lys
      and Arg was used in the hydrolyzate solution. However, there seemed to be a
      positive effect on Lys absorption when both amino acids were at high
      concentrations (30 and 75 mM, respectively). This type of studies will led us to
      test different formulations and/or additives to better understand the efficiency
      of AA supplementation as an alternative to in situ studies that are difficult to
      follow to design with the Pacific Bluefin Tuna.

PMID- 23001591
TI  - The respiratory compensation "point" as a determinant of O2 uptake kinetics?

PMID- 23001593
TI  - A dedicated automated injection system for dynamic contrast-enhanced MRI
      experiments in mice.
AB  - PURPOSE: To develop a reproducible small-animal dynamic contrast-enhanced (DCE)
      MRI set-up for mice through which volumes <100 MUL can be accurately and safely
      injected and to test this set-up by means of DCE measurements in resting muscle
      and tumor tissue. MATERIALS AND METHODS: The contrast agent (CA) injection system
      comprised 2 MR-compatible syringe pumps placed 50 cm from the 7T magnet bore
      where the fringe field is approximately 40 mT. Microbore tubing and T-connector,
      close to the injection site, minimized dead volume (<10 MUL). For DCE-MRI
      measurements in 8 CB-17 SCID mice with 1500-2500 mm(3) large orthotopic
      neuroblastoma, a bolus of 10-fold-diluted Gd-DTPA CA solution (0.1 mmol/kg) was
      delivered (5 MUL/s), followed by a 50-MUL saline flush. Retro-orbital injections
      were given instead of tail vein injections, because the peripheral vasculature
      was reduced because of large tumor burden. RESULTS: The CA injection was
      successful in 19 of 24 experiments. Optical assessment showed minimal dispersion
      of ink-colored CA bolus. Mean (+/- SD) pharmacokinetic parameters retrieved from
      DCE-MRI examinations in resting muscle (K(trans) = 0.038 +/- 0.025 min(-1), k(ep)
      = 0.66 +/- 0.48 min(-1), v(e) = 0.060 +/- 0.014, v(p) = 0.033 +/- 0.021) and
      tumor (K(trans) = 0.082 +/- 0.071 min(-1), k(ep) = 0.82 +/- 0.80 min(-1), v(e) =
      0.121 +/- 0.075, v(p) = 0.093 +/- 0.051) agreed with those reported previously.
      CONCLUSION: We successfully designed and implemented a DCE-MRI set-up system with
      short injection lines and low dead volume. The system can be used at any field
      strength with the syringe pumps placed at a sufficiently low fringe field (<40
      mT).

PMID- 23001594
TI  - Familial prostate cancer and HOXB13 founder mutations: geographic and
      racial/ethnic variations.

PMID- 23001595
TI  - Temperature-dependent capture of water molecules by saddle-shaped hexanuclear
      carboxylate cycloclusters in a (3,18)-connected metal-organic framework.
AB  - A new (3,18)-connected 3D metal-organic framework [Co(PYNT)(H(2)O)(2)](n) (ZZU-1)
      (H(2)PYNT=5-(3'-carboxylphenyl) nicotic acid) has been reported. Amazingly, ZZU-1
      captures water molecules and transforms into the hydrated framework
      {[Co(3)(PYNT)(3)(H(2)O)(6)]?H(2)O}(n) (ZZU-2) at 160  degrees C in refluxing
      hydrated DMF, but not at 100  degrees C in refluxing neat water or from the
      solvothermal synthesis conducted at 90  degrees C.

PMID- 23001596
TI  - Isolation of UVC-tolerant bacteria from the hyperarid Atacama Desert, Chile.
AB  - Martian surface microbial inhabitants would be challenged by a constant and
      unimpeded flux of UV radiation, and the study of analog model terrestrial
      environments may be of help to understand how such life forms could survive under
      this stressful condition. One of these environments is the Atacama Desert
      (Chile), a well-known Mars analog due to its extreme dryness and intense solar UV
      radiation. Here, we report the microbial diversity at five locations across this
      desert and the isolation of UVC-tolerant microbial strains found in these sites.
      Denaturing gradient gel electrophoresis (DGGE) of 16S rDNA sequences obtained
      from these sites showed banding patterns that suggest distinct and complex
      microbial communities. Analysis of 16S rDNA sequences obtained from UV-tolerant
      strains isolated from these sites revealed species related to the Bacillus and
      Pseudomonas genera. Vegetative cells of one of these isolates, Bacillus S3.300-2,
      showed the highest UV tolerance profile (LD(10) = 318 J m(2)), tenfold higher
      than a wild-type strain of Escherichia coli. Thus, our results show that the
      Atacama Desert harbors a noteworthy microbial community that may be considered
      for future astrobiological-related research in terms of UV tolerance.

PMID- 23001597
TI  - Food intake and body weight responses to intermittent vs. continuous gastric
      electrical stimulation in diet-induced obese rats.
AB  - BACKGROUND: Gastric electrical stimulation (GES) has recently been introduced as
      a potential therapy for the treatment of obesity. The main challenge for the new
      generation of devices is to achieve desired clinical outcomes at a suitably low
      level of energy consumption. The aim of this study is to compare the
      effectiveness of GES with continuous and intermittent duty cycles in reducing
      food intake and body weight in diet-induced obesity-prone rats. METHODS: In macro
      duty cycle experiment, 40 rats were divided into groups to receive a sham GES,
      continuous GES, or intermittent GES (15 min On-45 min Off or 15 min On-15 min
      Off) for 28 days. In micro duty cycle experiment, 18 rats received cross-over
      treatment of continuous stimulation, 60 % time cycle or 40 % time cycle. Food
      intake, body weight, gastric emptying and ghrelin level were measured to evaluate
      the effect of different GES. RESULTS: GES with macro duty cycle intensity
      dependently reduced mean daily food intake increase by 18.6, 10.2 and -6.0 %
      compared to 42.7 % with sham GES and body weight gain by 6.1 %, 3.4 and -0.8 %
      compared to 5 % with sham GES. Daily food intake decreased with increasing micro
      duty cycle intensity, averaging 16.5, 15.6 and 13.7 g/day under 40 % cycle, 60 %
      cycle and continuous stimulation respectively. Gastric emptying was intensity
      dependently delayed by GES. GES has no effect in modulating plasma ghrelin level.
      CONCLUSIONS: GES energy-dependently reduces food intake, body weight and gastric
      emptying. Peripheral modulation of plasma ghrelin level is not related to the GES
      effects.

PMID- 23001599
TI  - The true meaning of IFSO.

PMID- 23001598
TI  - Indications and mid-term results of conversion from sleeve gastrectomy to Roux-en
      Y gastric bypass.
AB  - Sleeve gastrectomy (SG) is currently considered as a primary bariatric surgery.
      This is because of its relative simplicity and satisfactory results. As observed
      with other bariatric procedures, surgeons are confronted with insufficient weight
      loss or weight regain, insufficient resolution of metabolic disorders, and
      intractable severe reflux. A retrospective analysis of conversion from SG to Roux
      en-Y gastric bypass (RYGBP) was performed to assess weight loss, diabetes
      resolution, and relief of reflux symptoms. The mean interval between the two
      procedures was almost 24 months. Eighteen patients underwent conversion from SG
      to RYGBP for insufficient weight loss (n = 9), severe reflux (n = 6), and
      persistence of type 2 diabetes mellitus (T2DM) (n = 3). The median follow-up was
      15.5 months. Weight loss was significantly improved with a mean percentage of
      excess of body mass index loss at 64.6 % after conversion versus 47.1 % before
      conversion. All reflux symptoms were immediately relieved without any medication
      at the end of the follow-up. The three patients who had an operation for
      persistence of T2DM are now free of medication. Only one postoperative
      complication was observed as a small bowel injury, which was treated surgically.
      Conversion from SG to RYGBP is safe. Severe reflux is definitely treated and is
      an incontestable indication with this procedure. Additionally, weight loss and
      diabetes are clinically improved. Our results appear to be similar to those with
      a primary RYGBP.

PMID- 23001600
TI  - Invited comment on Selvaggi et al.: Is omitting pouchography before ileostomy
      takedown safe after negative clinical examination in asymptomatic patients with
      pelvic ileal pouch? An observational study.

PMID- 23001601
TI  - Treatment of acute multiorgan dysfunction occurring in congenital adrenal
      hyperplasia.

PMID- 23001602
TI  - The serum undercarboxylated osteocalcin level and the diet of a Japanese
      population: results from the Kyushu and Okinawa Population Study (KOPS).
AB  - The elevated serum undercarboxylated osteocalcin (ucOC) level is related to
      osteoporosis. In Japan, vitamin K intake is lower, and the incidence of hip
      fractures noticeably higher in northern Kyushu than in other areas. The study was
      done to determine the serum ucOC levels in a Japanese population and its
      association with diet and glucose metabolism. The data of 3,658 healthy adults
      aged 40-69 (1,373 men and 2,285 women) who lived in northern Kyushu area were
      analyzed. The data included anthropometric measurements and a self-reported
      personal interview on daily intake of foods. The serum ucOC level of each
      participant was measured by electrochemiluminescence immunoassay. Glycohemoglobin
      A1c (HbA1c), fasting plasma glucose, and serum insulin concentrations were
      measured. The median serum ucOC level of the women (4.65 ng/mL) was significantly
      higher than that of the men (3.04 ng/mL) (P = 0.0021). The age-specific ucOC
      levels of the men decreased significantly with age. In contrast, the ucOC levels
      of the women aged >=50 were elevated, but the levels varied markedly within the
      other age groups. For both men and women, multivariate analysis identified a
      daily diet rich in vitamin K and HbA1c level as independently having a
      significant, negative relationship to serum ucOC level. Our study indicates that
      the serum ucOC decreases with age in men, increases postmenopausally in women,
      and correlates inversely with dietary consumption of certain foods and with
      fasting glucose and HbA1c level.

PMID- 23001603
TI  - Hunting osteoporosis susceptibility genes: bigger is better but diverse is also
      welcome.

PMID- 23001604
TI  - Diffusion-weighted MR imaging in liver metastases of colorectal cancer:
      reproducibility and biological validation.
AB  - OBJECTIVES: Before diffusion-weighted imaging (DWI) can be implemented in
      standard clinical practice for response monitoring, data on reproducibility are
      needed to assess which differences outside the range of normal variation can be
      detected in an individual patient. In this study we assessed the reproducibility
      of the apparent diffusion coefficient (ADC) values in colorectal liver
      metastases. To provide a biological basis for these values, their relation with
      histopathology was assessed. METHODS: DWI was performed twice in 1 week in
      patients scheduled for metastasectomy of colorectal liver metastases. Correlation
      between ADC values and apoptosis marker p53, anti-apoptotic protein BCL-2,
      proliferation marker Ki67 and serum vascular endothelial growth factor (VEGF)
      concentration were assessed. RESULTS: A good reproducibility coefficient of the
      mean ADC (coefficient of reproducibility 0.20 * 10(-3) mm(2)/s) was observed in
      colorectal liver metastases (n = 21). The ADC value was related to the
      proliferation index and BCL-2 expression of the metastases. Furthermore, in
      metastases recently treated with systemic therapy, the ADC was significantly
      higher (1.27 * 10(-3) mm(2)/s vs 1.05 * 10(-3) mm(2)/s, P = 0.02). CONCLUSIONS:
      The good reproducibility, correlation with histopathology and implied sensitivity
      for systemic treatment-induced anti-tumour effects suggest that DWI might be an
      excellent tool to monitor response in metastatic colorectal cancer.

PMID- 23001605
TI  - Immediate effects of the initial FDA notification on the use of surgical mesh for
      pelvic organ prolapse surgery in medicare beneficiaries.
AB  - AIMS: Prompted by increased reports of complications with the use of mesh for
      pelvic organ prolapse (POP) surgery, the FDA issued an initial public health
      notification (PHN) in 2008. We proposed to determine if the numbers of POP cases
      augmented with surgical mesh performed in U.S. Medicare beneficiaries changed
      relative to this PHN. METHODS: Using administrative healthcare claims for
      beneficiaries enrolled in the U.S. Medicare program from 2008 to 2009, we
      identified women who underwent POP surgery with and without surgical mesh by
      procedural and diagnosis coding. In addition to comparing cases with and without
      mesh, we also calculated rates (number of cases per 100,000 female beneficiaries)
      and compared these relative to the timing of the PHN. RESULTS: We identified
      104,185 POP procedures, of which 27,839 (26.7%) included mesh material and 76,346
      (73.3%) did not. Between the last three quarters of 2008 and the first three of
      2009, the rates of mesh cases increased (40.3-42.1, P < 0.001) and those without
      mesh decreased (115.5-111.4, P < 0.001). Inpatient procedures decreased and
      outpatient procedures increased for both those with and without mesh
      augmentation. For inpatient procedures, the relative use of biologic graft and
      synthetic mesh material did not vary over the study period. CONCLUSIONS: A
      substantial number of Medicare beneficiaries underwent mesh POP procedures in
      2008-2009. However, despite the PHN cautioning about potential mesh
      complications, the numbers of mesh cases continued to rise in the immediate
      period after the PHN.

PMID- 23001606
TI  - Molecular studies on the origin of the Hb G-Coushatta mutation in Denizli
      province of Turkey.

PMID- 23001607
TI  - Non-coding RNAs and EZH2 interactions in cancer: long and short tales from the
      transcriptome.
AB  - A large amount of data indicates that non-coding RNAs represent more than the
      "dark matter" of the genome. Both microRNAs and long non-coding RNAs are involved
      in several fundamental biologic processes, and their deregulation may lead in
      oncogenesis. Interacting with the Polycomb-repressive complex 2 subunit EZH2,
      they could affect the expression of protein-coding genes and form feedback
      networks and autoregulatory loops. They can also form networks with upstream and
      downstream important factors, in which EZH2 represent the stabilizing factor of
      the pathway. As such non-coding RNAs affect the epigenetic modifications leading
      to malignant transformation.

PMID- 23001608
TI  - Nutritional problems, overhydration and the association with quality of life in
      elderly dialysis patients.
AB  - PURPOSE: The aim of this pilot study was to describe the hydration and
      nutritional status of a cohort of elderly dialysis patients and to explore the
      association between these parameters and the quality of life (QoL). METHODS: All
      patients over 75 years of age being in chronic dialysis by January 2008 at 3
      dialysis units (n=34) were asked to participate in this pilot study, 24 patients
      were entered. Hydration status was assessed by bioimpedance spectroscopy (BIS)
      and nutritional status by the subjective global assessment (SGA), BIS,
      anthropometric measures and biochemical parameters. Based on these assessments
      the patients were classified as being cachectic or not according to newly defined
      criteria. QoL was measured using the SF-36. RESULTS: The results showed cachexia
      in 6 (25%), 37.5% had a body mass index below 24, whereas according to SGA 91%
      were malnourished. BIS showed low lean tissue index in 46% and overhydration in
      35% of the patients. Compared to non-cachectic and normohydrated, cachectic and
      overhydrated patients reported consistently poorer QoL. For cachectic patients,
      the differences were clinically significant for all SF-36. BIS was easily
      applicable when used before dialysis. CONCLUSIONS: The high frequency of
      nutritional deficits in this study calls for more attention to nutritional status
      in elderly dialysis patients. There is a need for a general agreement on how
      nutritional status should be assessed and reported, both in clinics and in
      research.

PMID- 23001609
TI  - Milk-alkali syndrome sine alkalosis; an elusive cause of intermittent
      hypercalcemia.

PMID- 23001610
TI  - An unexpected presentation: minimal change disease in an adult with treatment
      naive hepatitis C.
AB  - Minimal change disease is the most common glomerular disease affecting children;
      its prevalence among adults, however, is eclipsed by other glomerular
      pathologies. Each of these diseases has a number of classic associations, such as
      membranoproliferative glomerulonephritis with hepatitis C. We report the case of
      a middle-aged African-American male who presented with the nephrotic syndrome and
      acute renal failure and was concomitantly diagnosed with a new hepatitis C
      infection. He also had a history of urethral strictures with potential reflux
      nephropathy, which--in combination with his African-American race--also made
      focal segmental glomerulosclerosis a diagnostic possibility. Full laboratory
      evaluation did not distinguish the cause of his massive proteinuria; subsequent
      renal biopsy ultimately revealed minimal change disease. A full course of high
      dose steroids eventually reduced his proteinuria, after which his renal failure
      resolved as well without need for hemodialysis.

PMID- 23001611
TI  - The kidney in space.
AB  - Renal adaptation in space has been studied during various space missions since
      the early 70s. Technical and financial disadvantages of performing experiments
      under real microgravity conditions have warranted the conductance of relative
      studies under simulated weightlessness on earth. Arriving in microgravity leads
      to a redistribution of body fluids to the upper part of the body and an
      exaggerated extravasation very early in-flight. Plasma volume as well as skin
      evaporation and oral hydration are reduced, while total body water seems to
      remain stable. Urinary sodium is diminished and a substantial amount of sodium is
      retained outside the intravascular space. Glomerular filtration rate shows a
      transient mild increase. Urinary albumin excretion is reduced although initial
      studies had demonstrated the opposite. Examination of renal histopathology after
      exposure to simulated microgravity in rats revealed glomerular atrophy,
      interstitial edema, and degeneration of renal tubular cells. Acute urinary
      retention which has been reported during spaceflights can lead to certain medical
      complications that could compromise an entire mission. Kidney stone formation is
      another important potential hazard for any manned spaceflight. Increased kidney
      stone formation in space is attributed to several factors including reduced fluid
      intake, hypercalciuria, and the presence of nanobacteria. Nutritional and
      pharmacological interventions are currently recommended as preventive measures
      against renal stone formation in space travelers.

PMID- 23001612
TI  - Attention-deficit hyperactivity disorder in patients with premature ejaculation:
      a pilot study.
AB  - PURPOSE: The etiology of both adult-type ADHD and PE is not completely
      understood, but the studies revealing common etiologic factors for both
      conditions suggest a high likelihood of coexistence. We aimed to find out the
      prevalence of ADHD among adult males with lifetime PE. METHODS: The patients with
      lifetime PE were included in the study. Both patients and controls were evaluated
      with the 10-item premature ejaculation index of Althof and Rosen for premature
      ejaculation, Wender Utah rating scale (WURS) and Conner's adult ADHD rating
      scales (CAARS) for determining the presence of attention-deficit hyperactivity
      disorder syndrome. RESULTS: A total of 38 patients and 27 controls were included
      in the study. Patient and control groups were similar in terms of age and (p <
      0.878), but different IELT (p < 0.001). ADHD was detected in 16 (42.1 %) of
      patients with PE, while ADHD symptoms were detected in only 1 (3.7 %) of control
      patients. Distribution of patients in the study group according to ADHD types was
      as follows: Type 1, Type 2, Type 3 in 2 (5.3 %), 4 (10.5 %), and 10 (26.3 %)
      patients, respectively. CONCLUSIONS: ADHD is significantly more frequent among
      patients with PE than controls. The close relationships between these two
      diseases must be examined by prospective studies.

PMID- 23001614
TI  - Aerobic fitness after JDM--a long-term follow-up study.
AB  - OBJECTIVES: It has previously been shown that patients with active JDM have
      decreased aerobic fitness; however, it is not known whether these patients regain
      their physical fitness after recovery. The objective of this study was to
      investigate the long-term outcome of aerobic fitness in patients with JDM. We
      hypothesized that fitness (VO(2max)) is reduced compared with healthy controls in
      the years after active JDM. METHODS: A maximal exercise test was performed using
      a cycle ergometer. Results were compared with those of sex- and age-matched
      healthy controls. RESULTS: A total of 36 patients with JDM in remission were
      included, 2-36 years after disease onset. Twelve patients (33%) had normal
      VO(2max) and 24 patients (67%) had decreased VO(2max). Mean VO(2max) was higher
      in the healthy controls vs patients (P < 0.001, 95% CI -10.7, -4.4). A
      significant difference between patients with JDM and controls was observed for
      women (P < 0.001), men (P = 0.04), children < 18 years (P = 0.002) and adults >
      18 years (P = 0.01). The decreased VO(2max) was independent of the duration of
      remission, but it was associated with the duration of active disease. By linear
      regression, it was revealed that for every year of active disease, VO(2max) was
      reduced by 0.85 ml/min/kg on average (P < 0.001). CONCLUSION: This long-term
      follow-up study demonstrates that patients who have had JDM have persistently
      impaired fitness. This impairment is directly related to the duration of active
      disease.

PMID- 23001615
TI  - Anatomic study of the superior glenoid labrum.
AB  - The purpose of the study was to describe the normal anatomy of the glenoid labrum
      to help identification of pathology and guide surgical repair. Twenty dry bone
      scapulae and 19 cadaveric shoulders were examined. Light microscopy was performed
      on 12 radial slices through the glenoid. An external capsular circumferential
      ridge, 7-8 mm medial to the glenoid rim marks the attachment of the capsule. A
      separate internal labral circumferential ridge 4 mm central to the glenoid rim
      marks the interface between the labrum and articular cartilage. A superior
      posterior facet was found consistently on the glenoid. Two thirds of the long
      head of biceps arises from the supraglenoid tubercle, 6.6 mm from the glenoid
      face, the remainder from the labrum. The superior labrum is concave and is
      loosely attached to the articular cartilage and glenoid rim. Clefts and foramens
      are common superiorly. In contrast the anterior-inferior labrum is convex,
      attaches 4 mm central to the glenoid rim and has a strong attachment to articular
      cartilage and bone. Sublabral clefts, recesses, and holes are common, but only in
      the superior-anterior labrum. Lesions in other regions of the labrum are
      potentially pathological. A complex superior labrum tear that extends to involve
      the biceps anchor, should have the biceps anchor repaired to the supraglenoid
      tubercle (mean 6.6 mm off the glenoid face) and the labrum be repaired to the
      glenoid rim. The anteroinferior labrum should be repaired 4 mm onto the glenoid
      face. This study will aid in identifying pathological labral lesions and guide
      anatomic repairs.

PMID- 23001613
TI  - Pneumocystis jirovecii infection: an emerging threat to patients with rheumatoid
      arthritis.
AB  - Accompanying the increased use of biologic and non-biologic antirheumatic agents,
      patients with RA have been exposed to an increased risk of Pneumocystis jirovecii
      infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality
      in this population is higher than in HIV-infected individuals. Several guidelines
      and recommendations for HIV-infected individuals are available; however, such
      guidelines for RA patients remain less clear. Between 2006 and 2008 we
      encountered a clustering event of P. jirovecii infection among RA outpatients.
      Through our experience with this outbreak and a review of the recent medical
      literature regarding asymptomatic colonization and its clinical significance,
      transmission modes of infection and prophylaxis of PCP, we have learned the
      following lessons: PCP outbreaks among RA patients can occur through person-to
      person transmission in outpatient facilities; asymptomatic carriers serve as
      reservoirs and sources of infection; and short-term prophylaxis for eradication
      of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

PMID- 23001616
TI  - The investigation of the binding of 6-mercaptopurine to site I on human serum
      albumin.
AB  - 6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has
      been found active against human leukemias. The equilibrium dialysis, circular
      dichroism (CD) and molecular docking were employed to study the binding of 6-MP
      to human serum albumin (HSA). The binding of 6-MP to HSA in the equilibrium
      dialysis experiment was detected by measuring the displacement of 6-MP by
      specific markers for site I on HSA, warfarin (RWF), phenylbutazone (PhB) and n
      butyl p-aminobenzoate (ABE). It was shown, according to CD data, that binding of
      6-MP to HSA leads to alteration of HSA secondary structure. Based on the findings
      from displacement experiment and molecular docking simulation it was found that 6
      MP was located within binding cavity of subdomain IIA and the space occupied by
      site markers overlapped with that of 6-MP. Displacement of 6-MP by the RWF or PhB
      was not up the level expected for a competitive mechanism, therefore displacement
      of 6-MP was rather by non-cooperative than that the direct competition. Instead,
      in case of the interaction between ABE and 6-MP, when the little enhancement of
      the binding of ABE by 6-MP was found, the interaction could be via a positively
      cooperative mechanism.

PMID- 23001617
TI  - Quantitation of pH-induced aggregation in binary protein mixtures by dielectric
      spectroscopy.
AB  - This paper presents a quantitative approach for measuring pH-controlled protein
      aggregation using dielectric spectroscopy. The technique is demonstrated through
      two aggregation experiments, the first between beta-lactoglobulin (beta-Lg) and
      hen lysozyme (HENL) and the second between bovine serum albumin (BSA) and HENL.
      In both experiments, the formation of aggregates is strongly dependent on the
      solution pH and is clearly indicated by a decrease in the measured permittivity
      when the second protein is added. A quantifiable lower-bound on the ratio of
      proteins involved in the aggregation process is obtained from the permittivity
      spectra. Lower-bound aggregation ratios of 83 % for beta-Lg/HENL at pH 6.0 and 48
      % for BSA/HENL at pH 9.2 were consistent with turbidity measurements made on the
      same solutions.

PMID- 23001618
TI  - Functional MR cholangiography of the cystic duct and sphincter of Oddi using
      gadoxetate disodium: is a 30-minute delay long enough?
AB  - PURPOSE: To determine if excreted contrast is consistently visualized in the
      gallbladder and duodenum after a 30-minute delay using gadoxetate disodium
      enhanced MRI in patients without hepatobiliary disease. MATERIALS AND METHODS:
      Twenty-two patients without evidence of liver or biliary disease underwent
      gadoxetate disodium-enhanced magnetic resonance imaging (MRI) from February 17,
      2009 through October 3, 2011. The mean age was 45 years (range 25-72). T1
      weighted hepatobiliary phase images at 5, 10, 20, and 30 minutes after contrast
      injection were reviewed in consensus by two radiologists to determine the delay
      at which enhancement of the gallbladder and duodenum first occurred. RESULTS:
      Thirteen of 22 (59.1%) patients demonstrated duodenal filling by 20 minutes and
      16/22 (72.7%) filled by 30 minutes. The mean time to duodenal enhancement was
      19.9 minutes (range 11.4-30.2 min). Seventeen of 22 (77.3%) patients demonstrated
      gallbladder filling by 20 minutes and 21/22 (95.5%) filled by 30 minutes. The
      mean time to gallbladder enhancement was 16.5 minutes (range 4.4-30.2 min).
      CONCLUSION: A significant number of normal patients do not show duodenal filling
      by 30 minutes, while the majority fill the gallbladder by 30 minutes using
      functional MR cholangiography (fMRC) with gadoxetate disodium. These findings
      will guide fMRC protocol design for patients with suspected acute cholecystitis
      and sphincter of Oddi dysfunction.

PMID- 23001619
TI  - In vitro cell compatibility study of rose bengal-chitosan adhesives.
AB  - BACKGROUND AND OBJECTIVES: Photochemical tissue bonding (PTB) using rose bengal
      (RB) in conjunction with light is an alternative technique to repair tissue
      without suturing. It was recently demonstrated that laser-irradiated chitosan
      films, incorporating RB, bonded firmly to calf intestine in vitro. It is thus
      required to investigate the possible cytotoxic effects of the RB-chitosan
      adhesive on cells before testing its application to in vivo models. MATERIALS AND
      METHODS: Adhesive films, based on chitosan and containing ~0.1 wt% RB were
      fabricated. Their cytotoxicity was assessed by growing human and murine
      fibroblasts either in media in which adhesive strips had been incubated, or
      directly on the adhesive. The adhesive was either laser-irradiated or not. Cells
      were stained after 48 hours with Trypan blue and the number of live and dead
      cells was recorded for cell viability. RESULTS: Murine and human fibroblasts grew
      confluent on the adhesives with no apparent morphological changes or any
      exclusion zone. Cell numbers of murine fibroblasts were not significantly
      different when cultured in media that was extracted from irradiated (86 +/- 7%)
      and non-irradiated adhesive (89 +/- 4%). A similar result was obtained for the
      human fibroblasts. CONCLUSIONS: These findings support that the RB-chitosan films
      induced negligible toxicity and growth retardation in murine and human
      fibroblasts.

PMID- 23001620
TI  - Identification of successful clinical fMRI sessions in children: an objective
      approach.
AB  - PURPOSE: The term clinical functional magnetic resonance imaging (fMRI) describes
      an examination with direct clinical impact on the patient. Interpretation of
      clinical fMRI especially in children, however, is often difficult due to
      suboptimal data quality. The current gold standard is standardized visual
      evaluation. To evaluate such data in an automated and objective way, we developed
      an approach to identify successful sessions. METHODS: Average activation inside a
      predefined, task-specific region of interest (ROI) is compared with average
      activation in the rest of the brain, and their ratio (classification factor [Fc])
      is determined for different statistical thresholds (T). The approach was tested
      and validated using 239 clinical pediatric fMRI sessions (sensorimotor,
      perceptive /productive language). Performance was assessed in terms of
      sensitivity, specificity, and positive likelihood ratio. RESULTS: Best
      performance was found for Fc >= 2 and T >= 2.5, achieving a sensitivity of 0.87
      and specificity of 0.94. Comparing the different domains, sensitivity was lowest
      for language production tasks, mainly due to atypical activation foci.
      CONCLUSION: We demonstrate that an objective, automated framework for the
      classification of clinical pediatric fMRI sessions may provide important
      additional information, supporting visual evaluation, especially from
      sensorimotor and language perception domains. In the current form, atypical or
      strong network activation is not easily captured.

PMID- 23001621
TI  - Is there an ecological basis for species abundance distributions?
AB  - Community ecologists have attempted to explain species abundance distribution
      (SAD) shape for more than 80 years, but usually without relating SAD shape
      explicitly to ecological variables. We explored whether the scale (total
      assemblage abundance) and shape (assemblage evenness) of avifaunal SADs were
      related to ecological covariates. We used data on avifaunas, in-site habitat
      structure and landscape context that were assembled from previous studies; this
      amounted to 197 transects distributed across 16,000 km(2) of the box-ironbark
      forests of southeastern Australia. We used Bayesian conditional autoregressive
      models to link SAD scale and shape to these ecological covariates. Variation in
      SAD scale was relatable to some ecological covariates, especially to landscape
      vegetation cover and to tree height. We could not find any relationships between
      SAD shape and ecological covariates. SAD shape, the core component in SAD theory,
      may hold little information about how assemblages are governed ecologically and
      may result from statistical processes, which, if general, would indicate that SAD
      shape is not useful for distinguishing among theories of assemblage structure.

PMID- 23001622
TI  - Nitrogen limitation, 15N tracer retention, and growth response in intact and
      Bromus tectorum-invaded Artemisia tridentata ssp. wyomingensis communities.
AB  - Annual grass invasion into shrub-dominated ecosystems is associated with changes
      in nutrient cycling that may alter nitrogen (N) limitation and retention. Carbon
      (C) applications that reduce plant-available N have been suggested to give native
      perennial vegetation a competitive advantage over exotic annual grasses, but
      plant community and N retention responses to C addition remain poorly understood
      in these ecosystems. The main objectives of this study were to (1) evaluate the
      degree of N limitation of plant biomass in intact versus B. tectorum-invaded
      sagebrush communities, (2) determine if plant N limitation patterns are reflected
      in the strength of tracer (15)N retention over two growing seasons, and (3)
      assess if the strength of plant N limitation predicts the efficacy of carbon
      additions intended to reduce soil N availability and plant growth. Labile C
      additions reduced biomass of exotic annual species; however, growth of native A.
      tridentata shrubs also declined. Exotic annual and native perennial plant
      communities had divergent responses to added N, with B. tectorum displaying
      greater ability to use added N to rapidly increase aboveground biomass, and
      native perennials increasing their tissue N concentration but showing little
      growth response. Few differences in N pools between the annual and native
      communities were detected. In contrast to expectations, however, more (15)N was
      retained over two growing seasons in the invaded annual grass than in the native
      shrub community. Our data suggest that N cycling in converted exotic annual
      grasslands of the northern Intermountain West, USA, may retain N more strongly
      than previously thought.

PMID- 23001623
TI  - Biogeographic variation in behavioral and morphological responses to predation
      risk.
AB  - The expression of prey antipredator defenses is often related to ambient consumer
      pressure, and prey express greater defenses under intense consumer pressure.
      Predation is generally greater at lower latitudes, and antipredator defenses
      often display a biogeographic pattern. Predation pressure may also vary
      significantly between habitats within latitudes, making biogeographic patterns
      difficult to distinguish. Furthermore, invasive predators may also influence the
      expression of prey defenses in ecological time. The purpose of this study was to
      determine how these factors influence the strength of antipredator responses. To
      assess patterns in prey antipredator defenses based upon geographic range (north
      vs. south), habitat type (wave-protected vs. wave-exposed shores), and invasive
      predators, we examined how native rock (Cancer irroratus) and invasive green
      (Carcinus maenas) crab predators influence the behavioral and morphological
      defenses of dogwhelk (Nucella lapillus) prey from habitats that differ in wave
      exposure across an ~230 km range within the Gulf of Maine. The expression of
      behavioral and morphological antipredatory responses varied according to wave
      exposure, geographic location, and predator species. Dogwhelks from areas with an
      established history with green crabs exhibited the largest behavioral and
      morphological antipredator responses to green crabs. Dogwhelk behavioral
      responses to rock crabs did not vary between habitats or geographic regions,
      although morphological responses were greater further south where predation
      pressure was greatest. These findings suggest that dogwhelk responses to invasive
      and native predators vary according to geographic location and habitat, and are
      strongly affected by ambient predation pressure due to the invasion history of an
      exotic predator.

PMID- 23001624
TI  - Interactions between environmental stressors: the influence of salinity on host
      parasite interactions between Daphnia magna and Pasteuria ramosa.
AB  - Interactions between environmental stressors play an important role in shaping
      the health of an organism. This is particularly true in terms of the prevalence
      and severity of infectious disease, as stressors in combination will not always
      act to simply decrease the immune function of a host, but may instead interact to
      compound or even oppose the influence of parasitism on the health of an organism.
      Here, we explore the impact of environmental stress on host-parasite interactions
      using the water flea Daphnia magna and it is obligate parasite Pasteuria ramosa.
      Utilising an ecologically relevant stressor, we focus on the combined effect of
      salinity and P. ramosa on the fecundity and survival of the host, as well as on
      patterns of infectivity and the proliferation of the parasite. We show that in
      the absence of the parasite, host fecundity and survival was highest in the low
      salinity treatments. Once a parasite was introduced into the environment,
      however, salinity and parasitism acted antagonistically to influence both host
      survival and fecundity, and these patterns of disease were unrelated to infection
      rates or parasite spore loads. By summarising the form of interactions found in
      the broader Daphnia literature, we highlight how the combined effect of stress
      and parasitism will vary with the type of stressor, the trait used to describe
      the health of Daphnia and the host-parasite combination under observation. Our
      results highlight how the context-dependent nature of interactions between stress
      and parasitism inevitably complicates the link between environmental factors and
      the prevalence and severity of disease.

PMID- 23001625
TI  - Duodenal villous hypertrophy and upregulation of claudin-15 protein expression in
      lactating rats.
AB  - In lactation, the intestinal absorption of nutrients and minerals, especially
      calcium, is markedly enhanced to supply precursors for milk production. Little is
      known regarding the mechanism of this lactation-induced intestinal
      hyperabsorption. However, it has been postulated to result from villous
      hypertrophy with enlarged absorptive area and the upregulation of the cation
      selective tight junction protein claudin-15, which could form calcium-permeable
      paracellular pores, thereby enhancing the paracellular calcium absorption. Here,
      we demonstrated in the duodenum of 21-day lactating rats that there were
      increases in the villous height, villous width and crypt depth, which together
      led to expansion of absorptive surface area. Quantitative real-time PCR further
      showed that the mRNA levels of claudin-10 and -15 were increased in the duodenal
      mucosal cells of lactating rats as compared to age-matched unmated control rats.
      However, immunohistochemical analysis revealed the lactation-induced upregulation
      of claudin-15, but not claudin-10 protein expression in the duodenal villous
      cells. The present results, therefore, corroborated the previous hypothesis that
      lactation induced intestinal absorption of calcium and perhaps other cation
      minerals, in part, by increasing villous absorptive area and claudin-15 protein
      expression.

PMID- 23001626
TI  - Serum ischemic modified albumin levels might not be a marker of oxidative stress
      in patients with hypothyroidism.
AB  - Overt hypothyroidism and subclinical hypothyroidism are thought to be associated
      with atherosclerosis and a chronic ischemic process. Ischemic modified albumin
      (IMA) is a novel marker of ischemia. We examined serum IMA levels in patients
      with subclinical and overt hypothyroidism. We recruited patients who presented to
      our clinic for thyroid disease control. We compared demographic data, fasting
      blood sugar, serum lipid levels, and the prevalence of metabolic syndrome by the
      presence of overt, subclinical, and no hypothyroidism. Cobalt binding to albumin
      capacity was analyzed using a rapid colorimetric technique and compared among the
      groups. We assessed 11 men and 74 women with a mean age of 39.9 +/- 12 years. Of
      these, 48 (56.5 %) were euthyroid, 24 (28.2 %) had subclinical hypothyroidism,
      and 13 (15.3 %) had overt hypothyroidism. The groups did not differ significantly
      in terms of age; body mass index; waist circumference; systolic and diastolic
      blood pressures; levels of fasting and nonfasting blood sugar, high- and low
      density lipoproteins, and triglycerides; and the presence of metabolic syndrome.
      Mean serum IMA level also did not differ significantly among the groups: 0.20 +/-
      0.08 absorbance units (ABSU) in the euthyroid participants, 0.18 +/- 0.08 ABSU in
      those with subclinical hypothyroidism, and 0.20 +/- 0.09 ABSU in those with overt
      hypothyroidism (P = 0.754). Mean IMA values did not differ significantly by sex,
      cigarette use, the presence of metabolic syndrome, or the presence of thyroid
      autoantibodies. Serum IMA levels did not differ among patients with overt or
      subclinical hypothyroidism in this case-control study.

PMID- 23001627
TI  - Levothyroxine replacement therapy with vitamin E supplementation prevents
      oxidative stress and cognitive deficit in experimental hypothyroidism.
AB  - Hypothyroidism has a variety of adverse effects on cognitive function. The
      treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid
      patients. Antioxidant vitamin E supplementation could be useful in disturbances
      which are associated with oxidative stress and could effectively slow the
      progression of Alzheimer disease. Thus, the purpose of this study was to evaluate
      oxidative stress status of the serum and hippocampus in hypothyroidism and to
      examine the effects of levothyroxine replacement therapy with vitamin E
      supplementation on cognitive deficit. Sprague-Dawley rats were randomly divided
      into five groups: control group, PTU group, PTU + Vit E group, PTU + L-T4 group,
      and PTU + L-T4 + Vit E group. Serum and hippocampus malondialdehyde (MDA) levels
      were determined using the thiobarbituric-acid reactive substances method. Serum
      and hippocampus superoxide dismutase (SOD) levels were determined by measuring
      its ability to inhibit the photoreduction of nitroblue tetrazolium. Learning and
      memory was assessed by Morris water maze test. In the present study, we found
      that the rats of PTU + Vit E group spent less time to find the platform on days
      2, 3, 4, and 5 than the PTU group. Moreover, the rats of PTU + L-T4 + Vit E group
      spent less time to find the platform on days 4 and 5 than the PTU + L-T4 group.
      The time spent in the target quadrants was measured in the probe test and no
      difference was observed in all groups. Oxidative damage has been observed in the
      serum and hippocampus of hypothyroidism rat. SOD levels of serum and hippocampus
      tissue were significantly increased and MDA levels were significantly decreased
      in the PTU + Vit E and PTU + L-T4 + Vit E groups than the PTU and PTU + L-T4
      groups. Therefore, these findings indicate that levothyroxine replacement therapy
      with vitamin E supplementation may ameliorate cognitive deficit in PTU-induced
      hypothyroidism through the decrease of oxidative stress status.

PMID- 23001628
TI  - Tenax TA extraction to understand the rate-limiting factors in methyl-beta
      cyclodextrin-enhanced bioremediation of PAH-contaminated soil.
AB  - The effectiveness of many bioremediation systems for PAH-contaminated soil may be
      constrained by low contaminant bioaccessibility due to limited aqueous solubility
      or large sorption capacity. Information on the extent to which PAHs can be
      readily biodegraded is of vital importance in the decision whether or not to
      remediate a contaminated soil. In the present study the rate-limiting factors in
      methyl-beta-cyclodextrin (MCD)-enhanced bioremediation of PAH-contaminated soil
      were evaluated. MCD amendment at 10 % (w/w) combined with inoculation with the
      PAH-degrading bacterium Paracoccus sp. strain HPD-2 produced maximum removal of
      total PAHs of up to 35 %. The desorption of PAHs from contaminated soil was
      determined before and after 32 weeks of bioremediation. 10 % (w/w) MCD amendment
      (M2) increased the Tenax extraction of total PAHs from 12 to 30 % and promoted
      degradation by up to 26 % compared to 6 % in the control. However, the percentage
      of Tenax extraction for total PAHs was much larger than that of degradation.
      Thus, in the control and M2 treatment it is likely that during the initial phase
      the bioaccessibility of PAHs is high and biodegradation rates may be limited by
      microbial processes. On the other hand, when the soil was inoculated with the PAH
      degrading bacterium (CKB and MB2), the slowly and very slowly desorbing fractions
      (F sl and F vl ) became larger and the rate constants of slow and very slow
      desorption (k sl and k vl ) became extremely small after bioremediation,
      suggesting that desorption is likely rate limiting during the second, slow phase
      of biotransformation. These results have practical implications for site risk
      assessment and cleanup strategies.

PMID- 23001629
TI  - Biological degradation and solubilisation of coal.
AB  - This review focuses on ligninolytic fungi, soil bacteria, plants and root
      exudates in the degradation and solubilisation of low grade and waste coal and
      the interaction between these mutualistic biocatalysts. Coal represents a
      considerable portion of the total global fossil fuel reserve and continued demand
      for, and supply of this resource generates vast quantities of spoil and low grade
      waste. Large scale bioremediation technologies for the beneficiation of waste
      coal have unfortunately not yet been realised despite the many discoveries of
      microorganisms capable of lignite, lignin, and humic acid breakdown. Even so,
      solubilisation and depolymerization of low grade coal appears to involve either
      ligninolytic enzyme action or the production of alkaline substances or both.
      While the precise mechanism of coal biosolubilisation is unclear, a model for the
      phyto-biodegradation of low rank coal by mutualistic interaction between
      ligninolytic microorganisms and higher plants is proposed. Based on accumulated
      evidence this model suggests that solubilisation and degradation of lignite and
      waste coals commences upon plant root exudate and ligninolytic microorganism
      interaction, which is mutualistic, and includes soil bacteria and both
      mycorrhizal and non-mycorrhizal fungi. It is envisaged that this model and its
      further elaboration will aid in the development of functional technologies for
      commercial bioremediation of coal mine spoils, contribute to soil formation, and
      the overall biogeochemistry of organic carbon in the global ecosystem.

PMID- 23001630
TI  - Perylene bisimide dimer aggregates: fundamental insights into self-assembly by
      NMR and UV/Vis spectroscopy.
AB  - A novel perylene bisimide (PBI) dye bearing one solubilizing dialkoxybenzyl and
      one bulky 2,5-di-tert-butylphenyl substituent was synthesized and its aggregation
      behavior was analyzed by NMR and UV/Vis spectroscopy in various
      chloroform/methylcyclohexane (MCH) solvent mixtures. In the presence of no less
      than 10 vol % chloroform, exclusive self-assembly of this PBI dye into pi-stacked
      dimers was unambiguously confirmed by means of both concentration-dependent (1) H
      NMR and UV/Vis spectroscopic experiments. Based on ROESY NMR, a well-defined pi
      stacked dimer structure was determined and further corroborated by molecular
      modeling studies. By varying the solvent composition of chloroform and MCH, the
      solvent effects on the Gibbs free energy of PBI dimerization were elucidated and
      showed a pronounced nonlinearity between lower and higher MCH contents. This
      observation could be related to a further growth process of dimers into larger
      aggregates that occurs in the absence of chloroform, which is required to solvate
      the aromatic pi surfaces. With the help of a single-crystal structure analysis
      for a related PBI dye, a structural model could be derived for the extended
      aggregates that are still composed of defined pi-pi-stacked PBI dimer entities.

PMID- 23001631
TI  - The cognitive and behavioural profile of amyotrophic lateral sclerosis:
      application of the consensus criteria.
AB  - OBJECTIVE: The study aims to assess the spectrum of cognitive and behavioural
      disorders in patients affected by Amyotrophic Lateral Sclerosis (ALS) according
      to the recent consensus criteria [9]. The study also intends to assess the impact
      of physical disability on cognitive and behavioural abnormalities. METHODS:
      Detailed neurological, neuropsychological and neurobehavioral evaluations were
      administered to 23 ALS patients, 11 Lower Motor Neuron Disease (LMND) patients
      and 39 healthy controls. Strong et al.'s criteria [9] were applied to diagnose
      the presence of cognitive/behavioural impairment. Clinical and neuropsychological
      scores were used for group comparisons and correlation analyses. RESULTS: In
      comparison with LMND and controls, a subgroup of ALS patients (~30%) manifested
      executive dysfunction, which was severe enough to classify them as cognitively
      impaired. Action naming difficulties and short-term memory deficits were also
      observed. Aspontaneity, disorganization and mental rigidity reached clinical
      relevance in 20% of ALS patients. A small percentage of ALS patients (13%) also
      had comorbid dementia. The cognitive or behavioural status was not related to the
      clinical features of ALS. CONCLUSION: The use of consensus criteria for cognitive
      and behavioural impairment and the comparison with the LMND group proved useful
      in defining the spectrum of non-motor manifestations of ALS.

PMID- 23001632
TI  - New perspectives in transcranial magnetic stimulation: epilepsy, consciousness
      and the perturbational approach.
AB  - Transcranial magnetic stimulation (TMS) evolved from a simple method to stimulate
      the motor cortex to an invaluable tool for multiple diagnostic, research, and
      therapeutic applications. A further development of this noninvasive brain
      stimulation technique is concomitant electroencephalographic (EEG) recording
      during TMS. The theoretical underpinnings and the technological innovation of TMS
      EEG co-registration have opened new ways to study brain excitability in
      neurological conditions previously investigated with conventional EEG alone. A
      further advance in TMS research applications is the perturbational approach:
      magnetic pulses can interfere not only with dynamic, often pathological rhythms
      in epilepsy or altered consciousness states, but also modulate physiological
      states such as sleep and sleep deprivation. So applied, TMS-EEG co-registration
      can reveal different neurophysiological and behavioral patterns in the awake
      state, sleep or sleep deprivation. In this review, we discuss the use of TMS and
      TMS-EEG co-registration in epilepsy, a still rather limited although promising
      area of study. 

PMID- 23001633
TI  - Back and neck pain due to working in a cold environment: a cross-sectional study
      of male construction workers.
AB  - OBJECTIVE: To study whether work in a cold environment increased the risk of
      musculoskeletal symptoms in the neck and low back among construction workers.
      METHODS: This cross-sectional study is based on a cohort of male workers in the
      Swedish construction industry that participated in regular health examinations
      through a nationwide occupational health service. The analysis is based on
      workers examined from 1971 to 1974, who answered a questionnaire including
      questions about neck and back pain. The cohort consists of 134,754 male workers,
      including 16,496 office workers and foremen. The health examinations of the
      workers were conducted in provinces covering Sweden from the south to the north,
      and temperature data were collected for the provinces. In the analyses, the
      results were adjusted for age, BMI and use of nicotine. RESULTS: The prevalence's
      of neck and low back pain were higher among manual construction workers than
      among foremen and office workers (24.3 vs. 8.6 % and 16.5 vs. 6.2 %,
      respectively); the corresponding adjusted ORs for low back and neck pain were
      1.59 (95 % CI 1.52-1.66) and 1.39 (95 % CI 1.30-1.49), respectively. Workers in
      the northern and central provinces had higher ORs for low back and neck pain
      compared to workers in the southern province. The test for trends showed an
      increased risk of developing low back and neck pain with decreased outdoor
      temperature. CONCLUSIONS: Outdoor work in a cold environment may increase the
      risk of low back and neck pain.

PMID- 23001634
TI  - MAPT1 gene rs1052553 variant is unrelated with the risk for restless legs
      syndrome.
AB  - Mutations in the microtubule-associated protein tau gene (MAPT)  can cause
      frontotemporal dementia with Parkinsonism linked to the chromosome 17, and are
      associated with the risk for progressive supranuclear palsy, Parkinson's disease,
      corticobasal degeneration, and multiple system atrophy. We tried to establish,
      whether MAPT H1 discriminating haplotype single nucleotide polymorphisms (SNP)
      (rs1052553) is associated with the risk for restless legs syndrome (RLS). We
      studied the allelic and genotype frequencies of the SNP rs1052553 in 205 patients
      with RLS and 324 healthy controls using TaqMan genotyping. rs1052553 genotype and
      allelic frequencies did not differ significantly between patients with RLS and
      controls, and were unrelated with the age at onset of RLS, gender, family history
      of RLS, and severity of RLS. The results of the present study suggest that the
      SNP rs1052553 is not related with the risk for RLS.

PMID- 23001635
TI  - Re: Comments on "A randomized trial of urodynamic testing before stress
      incontinence surgery" (N Engl J Med. 2012 May 24;366(21):1987-1997) From the
      Italian Society of Urodynamics.

PMID- 23001636
TI  - Macroscopic and microsurgical varicocelectomy: what's the intraoperative
      difference?
AB  - PURPOSE: Many authors reported that microsurgical varicocelectomy was among the
      best treatment modalities for varicocele. However, the difference in
      intraoperative anatomic detail between macroscopic and microsurgical varicocele
      repair in the same spermatic cord has not been critically discussed. METHODS:
      Between August 2010 and February 2011, 32 men with 42 sides' grade 2-3 varicocele
      were enrolled in this study. One surgeon firstly mimicked the modified open
      varicocelectomy by identifying, isolating, and marking the presumed internal
      spermatic veins, lymphatics, and arteries. Another surgeon then checked the same
      spermatic cord using operating microscope to investigate the number of missed
      veins, to be ligated lymphatics and arteries in the "imitative" open
      varicocelectomy. RESULTS: There were significant differences in the average
      number of internal spermatic arteries (1.67 vs. 0.91), internal spermatic veins
      (6.45 vs. 4.31), and lymphatics (2.93 vs. 1.17) between microscopic and
      macroscopic procedure (P < 0.001, P < 0.001, P < 0.001, respectively). Meanwhile,
      an average of 2.14 +/- 1.26 internal spermatic veins was missed; among them, 1.63
      +/- 1.32 internal spermatic veins adherent to the preserved testicular artery
      were overlooked. The number of 0.69 +/- 0.84 lymphatics and 0.74 +/- 0.74
      arteries were to be ligated in "macroscopic varicocelectomy." A number of 1.07 +/
      1.11 lymphatics were neither identified nor ligated. In addition, in 2 cases,
      the vasal vessels of the vas deferens were to be ligated at macroscopic
      procedure. CONCLUSIONS: Microsurgical varicocelectomy could preserve more
      internal spermatic arteries and lymphatic and ligate more veins which may
      interpret the superiority of microsurgical varicocele repair.

PMID- 23001637
TI  - Low-level laser therapy (808 nm) reduces inflammatory response and oxidative
      stress in rat tibialis anterior muscle after cryolesion.
AB  - BACKGROUND AND OBJECTIVE: Muscle regeneration is a complex phenomenon, involving
      coordinated activation of several cellular responses. During this process,
      oxidative stress and consequent tissue damage occur with a severity that may
      depend on the intensity and duration of the inflammatory response. Among the
      therapeutic approaches to attenuate inflammation and increase tissue repair, low
      level laser therapy (LLLT) may be a safe and effective clinical procedure. The
      aim of this study was to evaluate the effects of LLLT on oxidative/nitrative
      stress and inflammatory mediators produced during a cryolesion of the tibialis
      anterior (TA) muscle in rats. MATERIAL AND METHODS: Sixty Wistar rats were
      randomly divided into three groups (n = 20): control (BC), injured TA muscle
      without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region
      was irradiated daily for 4 consecutive days, starting immediately after the
      lesion using a AlGaAs laser (continuous wave, 808 nm, tip area of 0.00785 cm(2) ,
      power 30 mW, application time 47 seconds, fluence 180 J/cm(2) ; 3.8 mW/cm(2) ;
      and total energy 1.4 J). The animals were sacrificed on the fourth day after
      injury. RESULTS: LLLT reduced oxidative and nitrative stress in injured muscle,
      decreased lipid peroxidation, nitrotyrosine formation and NO production, probably
      due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene
      expression, and decreased the inflammatory response as measured by gene
      expression of NF-kbeta and COX-2 and by TNF-alpha and IL-1beta concentration.
      CONCLUSION: These results suggest that LLLT could be an effective therapeutic
      approach to modulate oxidative and nitrative stress and to reduce inflammation in
      injured muscle.

PMID- 23001640
TI  - D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of
      blood pressure in hypertensive patients.
AB  - AIM: The aim of this study is to assess whether the haemostatic markers D-dimer,
      factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping
      status in treated hypertensive patients; so, as easy available laboratory data
      can predict non-dipping pattern and help with the selection of the patients whom
      circadian blood pressure should be re-examined. PATIENTS AND METHODS: Forty
      treated hypertensive patients with essential hypertension were included in the
      study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all
      patients. Daytime and nocturnal average systolic, diastolic and mean blood
      pressures were calculated. Patients were characterised as "non-dippers" on the
      basis of a less than 10 % decline in nocturnal blood pressure (BP); either
      systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function,
      FVIII activity and VWF antigen as marker of endothelial dysfunction were measured
      on plasma. The predictive efficiency was analysed by receiver operating
      characteristic (ROC) curves. Youden index was used for the estimation of the cut
      off points and the associated values for sensitivity and 1-specificity. RESULTS:
      Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers
      as compared with dippers, irrespective of the classification used (BP index); all
      P < 0.05. The ROC curves indicated a good diagnostic efficiency for D-dimer
      (AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755)
      and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern
      (systolic, diastolic or mean) in the study population; all P < 0.05. Among the
      three haemostatic markers, D-dimer presents the most satisfactory sensitivity/1
      specificity for the differentiation of non-dippers, with a cut-off point >168
      ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for
      diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375).
      CONCLUSION: In conclusion, D-dimer has a good predictive value for non-dipping
      pattern and the decision for the 24-h ambulatory blood pressure re-monitoring
      among dippers could rely on its values.

PMID- 23001639
TI  - Peri-aortic fat tissue and malnutrition-inflammation
      atherosclerosis/calcification syndrome in end-stage renal disease patients.
AB  - PURPOSE: Thoracic peri-aortic fat tissue (PFT) is considered as a metabolically
      active organ in atherosclerosis. Malnutrition, inflammation and
      atherosclerosis/calcification (MIAC) are the most commonly encountered risk
      factors of cardiovascular disease in end-stage renal disease (ESRD) patients.
      Calcification of the aorta was found to be an important cardiovascular risk
      marker predicting future events, morbidity and mortality in this population. We
      aimed to investigate the relationship between PFT, MIAC syndrome and thoracic
      aortic calcification (TAC) in ESRD patients. METHODS: Seventy-nine ESRD patients
      receiving hemodialysis (HD) or peritoneal dialysis (PD) and 20 control subjects
      were enrolled in this cross-sectional study. PFT and TAC were assessed using a 64
      MDCT scanner. Patients with serum albumin <3.5 g/dL were defined as patients with
      malnutrition; those with serum C-reactive protein level >10 mg/L had
      inflammation, and those with coronary artery calcification score (CACS) >10 had
      atherosclerosis/calcification. RESULTS: TAC and PFT were significantly higher in
      ESRD patients compared with control subjects. There was a statistically
      significant relationship between PFT and TAC in ESRD patients (r = 0.458, p <
      0.0001). PFT was found to be significantly increased when the MIAC components
      increased. PFT was positively associated with age, BMI, uric acid, hemoglobin and
      CAC. The multivariate analysis revealed that age and uric acid were independent
      predictors of increased PFT. Twenty-four (30.4 %) patients had none, 30 (37.9 %)
      had one component, 17 (21.5 %) had two components, and 8 (10.2 %) had all MIAC
      components. PFT was highest among patients having all three components (28.6
      cm(3)) and lowest among those who do not have the MIAC syndrome (8.54 cm(3)). TAC
      was highest among patients having all three components (179.2 HU) and lowest
      among those who do not have the MIAC syndrome (0 HU). CONCLUSIONS: We found a
      relationship between PFT and MIAC syndrome in ESRD patients.

PMID- 23001641
TI  - Can mycoplasma contribute to formation of prostate cancer?
AB  - PURPOSE: To reveal the possible role of mycoplasmas in the etiopathogenesis of
      prostate cancer. METHODS: In the study, prostate biopsy was performed on 62
      patients with an abnormal digital rectal examination and/or elevated PSA. The
      patients' age was between 62 and 77 (mean 65.4 years) years. Thirty-one patients
      had adenocarcinoma of the prostate histopathologically (group 1). From these
      patients, the specimens were divided into two subgroups as specimens with
      malignant findings (group 1A) and specimens with benign findings (group 1B). The
      control group consisted of 31 patients with benign prostatic hyperplasia (group
      2). In the specimens, the presence of mycoplasma DNA was investigated by the
      polymerase chain reaction method. RESULTS: The mycoplasma DNA was found to be
      positive in 11 (35.4 %) patients in group 1A and in 4 (12.9 %) patients in group
      1B. There was no mycoplasma DNA in the patients in group 2. The differences
      between group 1A and group 1B, and between group 1A and group 2 were
      statistically significant (p values, respectively, 0.006 and 0.0001).
      CONCLUSIONS: Our data supported the thesis that mycoplasma infections play a role
      in the etiopathogenesis of the prostate cancer.

PMID- 23001638
TI  - Myocardial regeneration of the failing heart.
AB  - Human heart failure (HF) is one of the leading causes of morbidity and mortality
      worldwide. Currently, heart transplantation and implantation of mechanical
      devices represent the only available treatments for advanced HF. Two alternative
      strategies have emerged to treat patients with HF. One approach relies on
      transplantation of exogenous stem cells (SCs) of non-cardiac or cardiac origin to
      induce cardiac regeneration and improve ventricular function. Another
      complementary strategy relies on stimulation of the endogenous regenerative
      capacity of uninjured cardiac progenitor cells to rebuild cardiac muscle and
      restore ventricular function. Various SC types and delivery strategies have been
      examined in the experimental and clinical settings; however, neither the ideal
      cell type nor the cell delivery method for cardiac cell therapy has yet emerged.
      Although the use of bone marrow (BM)-derived cells, most frequently exploited in
      clinical trials, appears to be safe, the results are controversial. Two recent
      randomized trials have failed to document any beneficial effects of intracardiac
      delivery of autologous BM mononuclear cells on cardiac function of patients with
      HF. The remarkable discovery that various populations of cardiac progenitor cells
      (CPCs) are present in the adult human heart and that it possesses limited
      regeneration capacity has opened a new era in cardiac repair. Importantly, unlike
      BM-derived SCs, autologous CPCs from myocardial biopsies cultured and
      subsequently delivered by coronary injection to patients have given positive
      results. Although these data are promising, a better understanding of how to
      control proliferation and differentiation of CPCs, to enhance their recruitment
      and survival, is required before CPCs become clinically applicable therapeutics. 

PMID- 23001642
TI  - Design of a randomized controlled trial of a web-based intervention to reduce
      cardiovascular disease risk factors among remote reservation-dwelling American
      Indian adults with type 2 diabetes.
AB  - We describe a randomized controlled trial, the Lakota Oyate Wicozani Pi Kte
      (LOWPK) trial, which was designed to determine whether a Web-based diabetes and
      nutritional intervention can improve risk factors related to cardiovascular
      disease (CVD) among a group of remote reservation-dwelling adult American Indian
      men and women with type 2 diabetes who are at high risk for CVD. Enrollment on a
      rolling basis of 180 planned participants began during 2009; an average 18-month
      follow-up was completed by June 2011. The primary outcome variable is change in
      glycosylated hemoglobin level after an average 18-month follow-up period.
      Secondary outcome variables include changes in low-density lipoprotein
      cholesterol, systolic blood pressure, body mass index, and smoking status, as
      well as an evaluation of intervention cost-effectiveness. If effective, the LOWPK
      trial may serve as a guide for future chronic disease intervention trials in
      remote, technologically challenged settings.

PMID- 23001643
TI  - Nanoelectroablation of human pancreatic carcinoma in a murine xenograft model
      without recurrence.
AB  - We have identified an effective nanoelectroablation therapy for treating
      pancreatic carcinoma in a murine xenograft model. This therapy initiates
      apoptosis in a nonthermal manner by applying low energy electric pulses 100 ns
      long and 30 kV/cm in amplitude to the tumor. We first identified the minimum
      pulse number required for complete ablation by treating 30 tumors. We found that
      the minimum number of pulses required to ablate the tumor with a single treatment
      is between 250 and 500 pulses. We settled on a single application of either 500
      or 1,000 pulses to treat pancreatic carcinomas in 19 NIH-III mice. Seventeen of
      the 19 treated tumors exhibited complete regression without recurrence. Three
      mice died of unknown causes within 3 months after treatment but 16 lived for 270
      302 days at which time we sacrificed them for histological analysis. In the 17
      untreated controls, the tumor grew so large that we had to sacrifice all of them
      within 4 months.

PMID- 23001644
TI  - Measuring the longitudinal relaxation time of GABA in vivo at 3 Tesla.
AB  - PURPOSE: To measure the in vivo longitudinal relaxation time T1 of GABA at 3
      Tesla (T). MATERIALS AND METHODS: J-difference edited single-voxel MR
      spectroscopy was used to isolate gamma-aminobutyric acid (GABA) signals. An
      increased echo time (80 ms) acquisition was used, accommodating the longer, more
      selective editing pulses required for symmetric editing-based suppression of co
      edited macromolecular signal. Acquiring edited GABA measurements at a range of
      relaxation times in 10 healthy participants, a saturation-recovery equation was
      used to model the integrated data. RESULTS: The longitudinal relaxation time of
      GABA was measured as T(1,GABA) = 1.31 +/- 0.16 s. CONCLUSION: The method
      described has been successfully applied to measure the T1 of GABA in vivo at 3T.

PMID- 23001645
TI  - Enantiomeric specificity of biologically significant Cu(II) and Zn(II) chromone
      complexes towards DNA.
AB  - Novel chiral Schiff base ligands (R)/(S)-2-amino-3-(((1-hydroxypropan-2
      yl)imino)methyl)-4H-chromen-4-one (L(1) and L(2)) derived from 2-amino-3
      formylchromone and (R/S)-2-amino-1-propanol and their Cu(II)/Zn(II) complexes
      (R1, S1, R2, and S2) were synthesized. The complexes were characterized by
      elemental analysis, infrared (IR), hydrogen ((1) H) and carbon ((13)C) nuclear
      magnetic resonance (NMR), electrospray ionization-mass spectra (ESI-MS), and
      molar conductance measurements. The DNA binding studies of the complexes with
      calf thymus were carried out by employing different biophysical methods and
      molecular docking studies that revealed that complexes R1 and S1 prefers the
      guanine-cytosine-rich region, whereas R2 and prefers the adenine-thymine residues
      in the major groove of DNA. The relative trend in K(b) values followed the order
      R1>S1>R2>S2. This observation together with the findings of circular dichroic and
      fluorescence studies revealed maximal potential of (R)-enantiomeric form of
      complexes to bind DNA. Furthermore, the absorption studies with mononucleotides
      were also monitored to examine the base-specific interactions of the complexes
      that revealed a higher propensity of Cu(II) complexes for guanosine-5'
      monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to
      thymidine-5'-monophosphate disodium salt. The cleavage activity of R1 and R2 with
      pBR322 plasmid DNA was examined by gel electrophoresis that revealed that they
      are good DNA cleavage agents; nevertheless, R1 proved to show better DNA cleavage
      ability. Topoisomerase II inhibitory activity of complex R1 revealed that the
      complex inhibits topoisomerase II catalytic activity at a very low concentration
      (25 MUM). Furthermore, in vitro antitumor activity of complexes R1 and S1 were
      screened against human carcinoma cell lines of different histological origin.

PMID- 23001647
TI  - Homologous Alkalophilic and Acidophilic L-Arabinose isomerases reveal region
      specific contributions to the pH dependence of activity and stability.
AB  - To study the pH dependence of l-arabinose isomerase (AI) activity and stability,
      we compared homologous AIs with their chimeras. This study demonstrated that an
      ionizable amino acid near the catalytic site determines the optimal pH (pH(opt))
      for activity, whereas the N-terminal surface R residues play an important role in
      determining the pH(opt) for stability.

PMID- 23001646
TI  - Heterotrophic archaea contribute to carbon cycling in low-pH, suboxic biofilm
      communities.
AB  - Archaea are widely distributed and yet are most often not the most abundant
      members of microbial communities. Here, we document a transition from Bacteria-
      to Archaea-dominated communities in microbial biofilms sampled from the Richmond
      Mine acid mine drainage (AMD) system (~pH 1.0, ~38 degrees C) and in laboratory
      cultivated biofilms. This transition occurs when chemoautotrophic microbial
      communities that develop at the air-solution interface sink to the sediment
      solution interface and degrade under microaerobic and anaerobic conditions. The
      archaea identified in these sunken biofilms are from the class Thermoplasmata,
      and in some cases, the highly divergent ARMAN nanoarchaeal lineage. In several of
      the sunken biofilms, nanoarchaea comprise 10 to 25% of the community, based on
      fluorescent in situ hybridization and metagenomic analyses. Comparative community
      proteomic analyses show a persistence of bacterial proteins in sunken biofilms,
      but there is clear evidence for amino acid modifications due to acid hydrolysis.
      Given the low representation of bacterial cells in sunken biofilms based on
      microscopy, we infer that hydrolysis reflects proteins derived from lysed cells.
      For archaea, we detected ~2,400 distinct proteins, including a subset involved in
      proteolysis and peptide uptake. Laboratory cultivation experiments using complex
      carbon substrates demonstrated anaerobic enrichment of Ferroplasma and Aplasma
      coupled to the reduction of ferric iron. These findings indicate dominance of
      acidophilic archaea in degrading biofilms and suggest that they play roles in
      anaerobic nutrient cycling at low pH.

PMID- 23001648
TI  - Anaerobic benzene oxidation by Geobacter species.
AB  - The abundance of Geobacter species in contaminated aquifers in which benzene is
      anaerobically degraded has led to the suggestion that some Geobacter species
      might be capable of anaerobic benzene degradation, but this has never been
      documented. A strain of Geobacter, designated strain Ben, was isolated from
      sediments from the Fe(III)-reducing zone of a petroleum-contaminated aquifer in
      which there was significant capacity for anaerobic benzene oxidation. Strain Ben
      grew in a medium with benzene as the sole electron donor and Fe(III) oxide as the
      sole electron acceptor. Furthermore, additional evaluation of Geobacter
      metallireducens demonstrated that it could also grow in benzene-Fe(III) medium.
      In both strain Ben and G. metallireducens the stoichiometry of benzene metabolism
      and Fe(III) reduction was consistent with the oxidation of benzene to carbon
      dioxide with Fe(III) serving as the sole electron acceptor. With benzene as the
      electron donor, and Fe(III) oxide (strain Ben) or Fe(III) citrate (G.
      metallireducens) as the electron acceptor, the cell yields of strain Ben and G.
      metallireducens were 3.2 * 10(9) and 8.4 * 10(9) cells/mmol of Fe(III) reduced,
      respectively. Strain Ben also oxidized benzene with anthraquinone-2,6-disulfonate
      (AQDS) as the sole electron acceptor with cell yields of 5.9 * 10(9) cells/mmol
      of AQDS reduced. Strain Ben serves as model organism for the study of anaerobic
      benzene metabolism in petroleum-contaminated aquifers, and G. metallireducens is
      the first anaerobic benzene-degrading organism that can be genetically
      manipulated.

PMID- 23001649
TI  - Choline and N,N-dimethylethanolamine as direct substrates for methanogens.
AB  - Choline (N,N,N-trimethylethanolamine), which is widely distributed in membrane
      lipids and is a component of sediment biota, has been shown to be utilized
      anaerobically by mixed prokaryote cultures to produce methane but not by pure
      cultures of methanogens. Here, we show that five recently isolated
      Methanococcoides strains from a range of sediments (Aarhus Bay, Denmark; Severn
      Estuary mudflats at Portishead, United Kingdom; Darwin Mud Volcano, Gulf of
      Cadiz; Napoli mud volcano, eastern Mediterranean) can directly utilize choline
      for methanogenesis producing ethanolamine, which is not further metabolized. Di-
      and monomethylethanolamine are metabolic intermediates that temporarily
      accumulate. Consistent with this, dimethylethanolamine was shown to be another
      new growth substrate, but monomethylethanolamine was not. The specific methanogen
      inhibitor 2-bromoethanesulfonate (BES) inhibited methane production from choline.
      When choline and trimethylamine are provided together, diauxic growth occurs,
      with trimethylamine being utilized first, and then after a lag (~7 days) choline
      is metabolized. Three type strains of Methanococcoides (M. methylutens, M.
      burtonii, and M. alaskense), in contrast, did not utilize choline. However, two
      of them (M. methylutens and M. burtonii) did metabolize dimethylethanolamine.
      These results extend the known substrates that can be directly utilized by some
      methanogens, giving them the advantage that they would not be reliant on
      bacterial syntrophs for their substrate supply.

PMID- 23001650
TI  - Exposure to solute stress affects genome-wide expression but not the polycyclic
      aromatic hydrocarbon-degrading activity of Sphingomonas sp. strain LH128 in
      biofilms.
AB  - Members of the genus Sphingomonas are important catalysts for removal of
      polycyclic aromatic hydrocarbons (PAHs) in soil, but their activity can be
      affected by various stress factors. This study examines the physiological and
      genome-wide transcription response of the phenanthrene-degrading Sphingomonas sp.
      strain LH128 in biofilms to solute stress (invoked by 450 mM NaCl solution),
      either as an acute (4-h) or a chronic (3-day) exposure. The degree of membrane
      fatty acid saturation was increased as a response to chronic stress. Oxygen
      consumption in the biofilms and phenanthrene mineralization activities of biofilm
      cells were, however, not significantly affected after imposing either acute or
      chronic stress. This finding was in agreement with the transcriptomic data, since
      genes involved in PAH degradation were not differentially expressed in stressed
      conditions compared to nonstressed conditions. The transcriptomic data suggest
      that LH128 adapts to NaCl stress by (i) increasing the expression of genes coping
      with osmolytic and ionic stress such as biosynthesis of compatible solutes and
      regulation of ion homeostasis, (ii) increasing the expression of genes involved
      in general stress response, (iii) changing the expression of general and specific
      regulatory functions, and (iv) decreasing the expression of protein synthesis
      such as proteins involved in motility. Differences in gene expression between
      cells under acute and chronic stress suggest that LH128 goes through changes in
      genome-wide expression to fully adapt to NaCl stress, without significantly
      changing phenanthrene degrading activity.

PMID- 23001651
TI  - Seasonal variations of indoor microbial exposures and their relation to
      temperature, relative humidity, and air exchange rate.
AB  - Indoor microbial exposure has been related to adverse pulmonary health effects.
      Exposure assessment is not standardized, and various factors may affect the
      measured exposure. The aim of this study was to investigate the seasonal
      variation of selected microbial exposures and their associations with
      temperature, relative humidity, and air exchange rates in Danish homes. Airborne
      inhalable dust was sampled in five Danish homes throughout the four seasons of 1
      year (indoors, n = 127; outdoors, n = 37). Measurements included culturable fungi
      and bacteria, endotoxin, N-acetyl-beta-d-glucosaminidase, total inflammatory
      potential, particles (0.75 to 15 MUm), temperature, relative humidity, and air
      exchange rates. Significant seasonal variation was found for all indoor microbial
      exposures, excluding endotoxin. Indoor fungi peaked in summer (median, 235
      CFU/m(3)) and were lowest in winter (median, 26 CFU/m(3)). Indoor bacteria peaked
      in spring (median, 2,165 CFU/m(3)) and were lowest in summer (median, 240
      CFU/m(3)). Concentrations of fungi were predominately higher outdoors than
      indoors, whereas bacteria, endotoxin, and inhalable dust concentrations were
      highest indoors. Bacteria and endotoxin correlated with the mass of inhalable
      dust and number of particles. Temperature and air exchange rates were positively
      associated with fungi and N-acetyl-beta-d-glucosaminidase and negatively with
      bacteria and the total inflammatory potential. Although temperature, relative
      humidity, and air exchange rates were significantly associated with several
      indoor microbial exposures, they could not fully explain the observed seasonal
      variations when tested in a mixed statistical model. In conclusion, the season
      significantly affects indoor microbial exposures, which are influenced by
      temperature, relative humidity, and air exchange rates.

PMID- 23001652
TI  - Chemotactic behavior of pathogenic and nonpathogenic Leptospira species.
AB  - We have developed a capillary tube assay in combination with real-time PCR to
      quantitate the number of chemoattracted Leptospira cells. We identified Tween 80,
      glucose, sucrose, and pyruvate as attractants for Leptospira cells; amino acids
      and vitamin B(12) were found to be nonchemotactic or weakly chemotactic. This
      assay has the general applicability to further our understanding of leptospiral
      chemotaxis.

PMID- 23001653
TI  - Different antibiotic resistance and sporulation properties within multiclonal
      Clostridium difficile PCR ribotypes 078, 126, and 033 in a single calf farm.
AB  - Clostridium difficile strains were sampled periodically from 50 animals at a
      single veal calf farm over a period of 6 months. At arrival, 10% of animals were
      C. difficile positive, and the peak incidence was determined to occur at the age
      of 18 days (16%). The prevalence then decreased, and at slaughter, C. difficile
      could not be isolated. Six different PCR ribotypes were detected, and strains
      within a single PCR ribotype could be differentiated further by pulsed-field gel
      electrophoresis (PFGE). The PCR ribotype diversity was high up to the animal age
      of 18 days, but at later sampling points, PCR ribotype 078 and the highly related
      PCR ribotype 126 predominated. Resistance to tetracycline, doxycycline, and
      erythromycin was detected, while all strains were susceptible to amoxicillin and
      metronidazole. Multiple variations of the resistance gene tet(M) were present at
      the same sampling point, and these changed over time. We have shown that PCR
      ribotypes often associated with cattle (ribotypes 078, 126, and 033) were not
      clonal but differed in PFGE type, sporulation properties, antibiotic
      sensitivities, and tetracycline resistance determinants, suggesting that multiple
      strains of the same PCR ribotype infected the calves and that calves were likely
      to be infected prior to arrival at the farm. Importantly, strains isolated at
      later time points were more likely to be resistant to tetracycline and
      erythromycin and showed higher early sporulation efficiencies in vitro,
      suggesting that these two properties converge to promote the persistence of C.
      difficile in the environment or in hosts.

PMID- 23001654
TI  - Comparison of the levels of bacterial diversity in freshwater, intertidal
      wetland, and marine sediments by using millions of illumina tags.
AB  - Sediment, a special realm in aquatic environments, has high microbial diversity.
      While there are numerous reports about the microbial community in marine
      sediment, freshwater and intertidal sediment communities have been overlooked.
      The present study determined millions of Illumina reads for a comparison of
      bacterial communities in freshwater, intertidal wetland, and marine sediments
      along Pearl River, China, using a technically consistent approach. Our results
      show that both taxon richness and evenness were the highest in freshwater
      sediment, medium in intertidal sediment, and lowest in marine sediment. The high
      number of sequences allowed the determination of a wide variety of bacterial
      lineages in all sediments for reliable statistical analyses. Principal component
      analysis showed that the three types of communities could be well separated from
      phylum to operational taxonomy unit (OTU) levels, and the OTUs from abundant to
      rare showed satisfactory resolutions. Statistical analysis (LEfSe) demonstrated
      that the freshwater sediment was enriched with Acidobacteria, Nitrospira,
      Verrucomicrobia, Alphaproteobacteria, and Betaproteobacteria. The intertidal
      sediment had a unique community with diverse primary producers (such as
      Chloroflexi, Bacillariophyta, Gammaproteobacteria, and Epsilonproteobacteria) as
      well as saprophytic microbes (such as Actinomycetales, Bacteroidetes, and
      Firmicutes). The marine sediment had a higher abundance of Gammaproteobacteria
      and Deltaproteobacteria, which were mainly involved in sulfate reduction in
      anaerobic conditions. These results are helpful for a systematic understanding of
      bacterial communities in natural sediment environments.

PMID- 23001655
TI  - Methicillin-resistant Staphylococcus aureus phage plaque size enhancement using
      sublethal concentrations of antibiotics.
AB  - Phage therapy presents an alternative approach against the emerging methicillin
      resistant Staphylococcus aureus (MRSA) threat. Some of the problems encountered
      during isolation of MRSA phages include the high prevalence of enteric phages in
      natural sources, nonspecific absorption of viable phage, and the formation of
      pinpoint or tiny plaques. The phage isolated in this study, MR-5, also formed
      tiny plaques against its host S. aureus ATCC 43300 (MRSA), making its detection
      and enumeration difficult. An improved method of increasing the plaque size of
      MRSA phage by incorporating sublethal concentrations of three different classes
      of antibiotics (inhibitors of protein synthesis) in the classical double-layer
      agar (DLA) method was investigated. The beta-lactam and quinolone antibiotics
      commonly employed in earlier studies for increasing the plaque size did not show
      any significant effect on the plaque size of isolated MR-5 phage. Linezolid
      (oxazolidinone class), tetracycline, and ketolide antibiotics brought significant
      enhancements (3 times the original size) in the plaque size of MR-5 phage. Prior
      treatment with these antibiotics resulted in significant reductions in the time
      of adsorption and the latent period of MR-5 phage. To rule out whether the action
      of linezolid (which brought the maximum increase in plaque size) was specific for
      a single phage only, its effect on the plaque size of seven other S. aureus
      specific phages was also assessed. Significant enhancements in the plaque size of
      these phages were observed. These results indicate that this modification can
      therefore safely be incorporated in the traditional DLA overlay method to search
      for new MRSA-virulent phages.

PMID- 23001656
TI  - Two enzymes of a complete degradation pathway for linear alkylbenzenesulfonate
      (LAS) surfactants: 4-sulfoacetophenone Baeyer-Villiger monooxygenase and 4
      sulfophenylacetate esterase in Comamonas testosteroni KF-1.
AB  - Complete biodegradation of the surfactant linear alkylbenzenesulfonate (LAS) is
      accomplished by complex bacterial communities in two steps. First, all LAS
      congeners are degraded into about 50 sulfophenylcarboxylates (SPC), one of which
      is 3-(4-sulfophenyl)butyrate (3-C(4)-SPC). Second, these SPCs are mineralized. 3
      C(4)-SPC is mineralized by Comamonas testosteroni KF-1 in a process involving 4
      sulfoacetophenone (SAP) as a metabolite and an unknown inducible Baeyer-Villiger
      monooxygenase (BVMO) to yield 4-sulfophenyl acetate (SPAc) from SAP (SAPMO
      enzyme); hydrolysis of SPAc to 4-sulfophenol and acetate is catalyzed by an
      unknown inducible esterase (SPAc esterase). Transcriptional analysis showed that
      one of four candidate genes for BVMOs in the genome of strain KF-1, as well as an
      SPAc esterase candidate gene directly upstream, was inducibly transcribed during
      growth with 3-C(4)-SPC. The same genes were identified by enzyme purification and
      peptide fingerprinting-mass spectrometry when SAPMO was enriched and SPAc
      esterase purified to homogeneity by protein chromatography. Heterologously
      overproduced pure SAPMO converted SAP to SPAc and was active with phenylacetone
      and 4-hydroxyacetophenone but not with cyclohexanone and progesterone. SAPMO
      showed the highest sequence homology to the archetypal phenylacetone BVMO (57%),
      followed by steroid BVMO (55%) and 4-hydroxyacetophenone BVMO (30%). Finally, the
      two pure enzymes added sequentially, SAPMO with NADPH and SAP, and then SPAc
      esterase, catalyzed the conversion of SAP via SPAc to 4-sulfophenol and acetate
      in a 1:1:1:1 molar ratio. Hence, the first two enzymes of a complete LAS
      degradation pathway were identified, giving evidence for the recruitment of
      members of the very versatile type I BVMO and carboxylester hydrolase enzyme
      families for the utilization of a xenobiotic compound by bacteria.

PMID- 23001657
TI  - Role of rpoS in Escherichia coli O157:H7 strain H32 biofilm development and
      survival.
AB  - The protein RpoS is responsible for mediating cell survival during the stationary
      phase by conferring cell resistance to various stressors and has been linked to
      biofilm formation. In this study, the role of the rpoS gene in Escherichia coli
      O157:H7 biofilm formation and survival in water was investigated. Confocal
      scanning laser microscopy of biofilms established on coverslips revealed a
      nutrient-dependent role of rpoS in biofilm formation, where the biofilm biomass
      volume of the rpoS mutant was 2.4- to 7.5-fold the size of its rpoS(+) wild-type
      counterpart in minimal growth medium. The enhanced biofilm formation of the rpoS
      mutant did not, however, translate to increased survival in sterile double
      distilled water (ddH(2)O), filter-sterilized lake water, or unfiltered lake
      water. The rpoS mutant had an overall reduction of 3.10 and 5.30 log(10) in
      sterile ddH(2)O and filter-sterilized lake water, respectively, while only minor
      reductions of 0.53 and 0.61 log(10) in viable counts were observed for the wild
      type form in the two media over a 13-day period, respectively. However, the
      survival rates of the detached biofilm-derived rpoS(+) and rpoS mutant cells were
      comparable. Under the competitive stress conditions of unfiltered lake water, the
      advantage conferred by the presence of rpoS was lost, and both the wild-type and
      knockout forms displayed similar declines in viable counts. These results suggest
      that rpoS does have an influence on both biofilm formation and survival of E.
      coli O157:H7 and that the advantage conferred by rpoS is contingent on the
      environmental conditions.

PMID- 23001658
TI  - Genetic barcodes for improved environmental tracking of an anthrax simulant.
AB  - The development of realistic risk models that predict the dissemination,
      dispersion and persistence of potential biothreat agents have utilized
      nonpathogenic surrogate organisms such as Bacillus atrophaeus subsp. globigii or
      commercial products such as Bacillus thuringiensis subsp. kurstaki. Comparison of
      results from outdoor tests under different conditions requires the use of
      genetically identical strains; however, the requirement for isogenic strains
      limits the ability to compare other desirable properties, such as the behavior in
      the environment of the same strain prepared using different methods. Finally,
      current methods do not allow long-term studies of persistence or reaerosolization
      in test sites where simulants are heavily used or in areas where B. thuringiensis
      subsp. kurstaki is applied as a biopesticide. To create a set of genetically
      heterogeneous yet phenotypically indistinguishable strains so that variables
      intrinsic to simulations (e.g., sample preparation) can be varied and the strains
      can be tested under otherwise identical conditions, we have developed a strategy
      of introducing small genetic signatures ("barcodes") into neutral regions of the
      genome. The barcodes are stable over 300 generations and do not impact in vitro
      growth or sporulation. Each barcode contains common and specific tags that allow
      differentiation of marked strains from wild-type strains and from each other.
      Each tag is paired with specific real-time PCR assays that facilitate
      discrimination of barcoded strains from wild-type strains and from each other.
      These uniquely barcoded strains will be valuable tools for research into the
      environmental fate of released organisms by providing specific artificial
      detection signatures.

PMID- 23001659
TI  - Effect of pH on the electrophoretic mobility of spores of Bacillus anthracis and
      its surrogates in aqueous solutions.
AB  - The electrophoretic mobility (EPM) of endospores of Bacillus anthracis and
      surrogates was measured in aqueous solution across a broad pH range and several
      ionic strengths. EPM values trended around phylogenetic clustering based on the
      16S rRNA gene. Measurements reported here provide new insight for Bacillus
      anthracis surrogate selection and for attachment/detachment and transport
      studies.

PMID- 23001660
TI  - Preferential utilization of D-lactate by Shewanella oneidensis.
AB  - Shewanella oneidensis couples oxidation of lactate to respiration of many
      substrates. Here we report that llpR (L-lactate-positive regulator, SO_3460)
      encodes a positive regulator of L-lactate utilization distinct from previously
      studied regulators. We also demonstrate D-lactate inhibition of L-lactate
      utilization in S. oneidensis, resulting in preferential utilization of the D
      isomer.

PMID- 23001661
TI  - "Methanoplasmatales," Thermoplasmatales-related archaea in termite guts and other
      environments, are the seventh order of methanogens.
AB  - The Euryarchaeota comprise both methanogenic and nonmethanogenic orders and many
      lineages of uncultivated archaea with unknown properties. One of these deep
      branching lineages, distantly related to the Thermoplasmatales, has been
      discovered in various environments, including marine habitats, soil, and also the
      intestinal tracts of termites and mammals. By comparative phylogenetic analysis,
      we connected this lineage of 16S rRNA genes to a large clade of unknown mcrA gene
      sequences, a functional marker for methanogenesis, obtained from the same
      habitats. The identical topologies of 16S rRNA and mcrA gene trees and the
      perfect congruence of all branches, including several novel groups that we
      obtained from the guts of termites and cockroaches, strongly suggested that they
      stem from the same microorganisms. This was further corroborated by two highly
      enriched cultures of closely related methanogens from the guts of a higher
      termite (Cubitermes ugandensis) and a millipede (Anadenobolus sp.), which
      represented one of the arthropod-specific clusters in the respective trees.
      Numerous other pairs of habitat-specific sequence clusters were obtained from the
      guts of other termites and cockroaches but were also found in previously
      published data sets from the intestinal tracts of mammals (e.g., rumen cluster C)
      and other environments. Together with the recently described
      Methanomassiliicoccus luminyensis isolated from human feces, which falls into
      rice cluster III, the results of our study strongly support the idea that the
      entire clade of "uncultured Thermoplasmatales" in fact represents the seventh
      order of methanogenic archaea, for which the provisional name
      "Methanoplasmatales" is proposed.

PMID- 23001664
TI  - Impact of sorbic acid on germination and outgrowth heterogeneity of Bacillus
      cereus ATCC 14579 spores.
AB  - Population heterogeneity complicates the predictability of the outgrowth kinetics
      of individual spores. Flow cytometry sorting and monitoring of the germination
      and outgrowth of single dormant spores allowed the quantification of acid-induced
      spore population heterogeneity at pH 5.5 and in the presence of sorbic acid. This
      showed that germination efficiency was not a good predictor for heterogeneity in
      final outgrowth.

PMID- 23001662
TI  - Characterizing Pneumocystis in the lungs of bats: understanding Pneumocystis
      evolution and the spread of Pneumocystis organisms in mammal populations.
AB  - Bats belong to a wide variety of species and occupy diversified habitats, from
      cities to the countryside. Their different diets (i.e., nectarivore, frugivore,
      insectivore, hematophage) lead Chiroptera to colonize a range of ecological
      niches. These flying mammals exert an undisputable impact on both ecosystems and
      circulation of pathogens that they harbor. Pneumocystis species are recognized as
      major opportunistic fungal pathogens which cause life-threatening pneumonia in
      severely immunocompromised or weakened mammals. Pneumocystis consists of a
      heterogeneous group of highly adapted host-specific fungal parasites that
      colonize a wide range of mammalian hosts. In the present study, 216 lungs of 19
      bat species, sampled from diverse biotopes in the New and Old Worlds, were
      examined. Each bat species may be harboring a specific Pneumocystis species. We
      report 32.9% of Pneumocystis carriage in wild bats (41.9% in Microchiroptera).
      Ecological and behavioral factors (elevation, crowding, migration) seemed to
      influence the Pneumocystis carriage. This study suggests that Pneumocystis-host
      association may yield much information on Pneumocystis transmission, phylogeny,
      and biology in mammals. Moreover, the link between genetic variability of
      Pneumocystis isolated from populations of the same bat species and their
      geographic area could be exploited in terms of phylogeography.

PMID- 23001663
TI  - Oxygen response of the wine yeast Saccharomyces cerevisiae EC1118 grown under
      carbon-sufficient, nitrogen-limited enological conditions.
AB  - Discrete additions of oxygen play a critical role in alcoholic fermentation.
      However, few studies have quantitated the fate of dissolved oxygen and its impact
      on wine yeast cell physiology under enological conditions. We simulated the range
      of dissolved oxygen concentrations that occur after a pump-over during the
      winemaking process by sparging nitrogen-limited continuous cultures with oxygen
      nitrogen gaseous mixtures. When the dissolved oxygen concentration increased from
      1.2 to 2.7 MUM, yeast cells changed from a fully fermentative to a mixed
      respirofermentative metabolism. This transition is characterized by a switch in
      the operation of the tricarboxylic acid cycle (TCA) and an activation of NADH
      shuttling from the cytosol to mitochondria. Nevertheless, fermentative ethanol
      production remained the major cytosolic NADH sink under all oxygen conditions,
      suggesting that the limitation of mitochondrial NADH reoxidation is the major
      cause of the Crabtree effect. This is reinforced by the induction of several key
      respiratory genes by oxygen, despite the high sugar concentration, indicating
      that oxygen overrides glucose repression. Genes associated with other processes,
      such as proline uptake, cell wall remodeling, and oxidative stress, were also
      significantly affected by oxygen. The results of this study indicate that
      respiration is responsible for a substantial part of the oxygen response in yeast
      cells during alcoholic fermentation. This information will facilitate the
      development of temporal oxygen addition strategies to optimize yeast performance
      in industrial fermentations.

PMID- 23001665
TI  - Inactivation of Salmonella enterica by UV-C light alone and in combination with
      mild temperatures.
AB  - The aim of this investigation was to study the efficacy of the combined processes
      of UV light and mild temperatures for the inactivation of Salmonella enterica
      subsp. enterica and to explore the mechanism of inactivation. The doses to
      inactivate the 99.99% (4D) of the initial population ranged from 18.03
      (Salmonella enterica serovar Typhimurium STCC 878) to 12.75 J ml(-1) (Salmonella
      enterica serovar Enteritidis ATCC 13076). The pH and water activity of the
      treatment medium did not change the UV tolerance, but it decreased exponentially
      by increasing the absorption coefficient. An inactivating synergistic effect was
      observed by applying simultaneous UV light and heat treatment (UV-H). A less
      synergistic effect was observed by applying UV light first and heat subsequently.
      UV did not damage cell envelopes, but the number of injured cells was higher
      after a UV-H treatment than after heating. The synergistic effect observed by
      combining simultaneous UV and heat treatment opens the possibility to design
      combined treatments for pasteurization of liquid food with high UV absorptivity,
      such as fruit juices.

PMID- 23001666
TI  - Quantitative analysis of the modes of growth inhibition by weak organic acids in
      Saccharomyces cerevisiae.
AB  - Weak organic acids are naturally occurring compounds that are commercially used
      as preservatives in the food and beverage industries. They extend the shelf life
      of food products by inhibiting microbial growth. There are a number of theories
      that explain the antifungal properties of these weak acids, but the exact
      mechanism is still unknown. We set out to quantitatively determine the
      contributions of various mechanisms of antifungal activity of these weak acids,
      as well as the mechanisms that yeast uses to counteract their effects. We
      analyzed the effects of four weak organic acids differing in lipophilicity
      (sorbic, benzoic, propionic, and acetic acids) on growth and intracellular pH
      (pH(i)) in Saccharomyces cerevisiae. Although lipophilicity of the acids
      correlated with the rate of acidification of the cytosol, our data confirmed that
      not initial acidification, but rather the cell's ability to restore pH(i), was a
      determinant for growth inhibition. This pH(i) recovery in turn depended on the
      nature of the organic anion. We identified long-term acidification as the major
      cause of growth inhibition under acetic acid stress. Restoration of pH(i), and
      consequently growth rate, in the presence of this weak acid required the full
      activity of the plasma membrane ATPase Pma1p. Surprisingly, the proposed anion
      export pump Pdr12p was shown to play an important role in the ability of yeast
      cells to restore the pH(i) upon lipophilic (sorbic and benzoic) acid stress,
      probably through a charge interaction of anion and proton transport.

PMID- 23001667
TI  - Effects of iron and nitrogen limitation on sulfur isotope fractionation during
      microbial sulfate reduction.
AB  - Sulfate-reducing microbes utilize sulfate as an electron acceptor and produce
      sulfide that is depleted in heavy isotopes of sulfur relative to sulfate. Thus,
      the distribution of sulfur isotopes in sediments can trace microbial sulfate
      reduction (MSR), and it also has the potential to reflect the physiology of
      sulfate-reducing microbes. This study investigates the relationship between the
      availability of iron and reduced nitrogen and the magnitude of S-isotope
      fractionation during MSR by a marine sulfate-reducing bacterium, DMSS-1, a
      Desulfovibrio species, isolated from salt marsh in Cape Cod, MA. Submicromolar
      levels of iron increase sulfur isotope fractionation by about 50% relative to
      iron-replete cultures of DMSS-1. Iron-limited cultures also exhibit decreased
      cytochrome c-to-total protein ratios and cell-specific sulfate reduction rates
      (csSRR), implying changes in the electron transport chain that couples carbon and
      sulfur metabolisms. When DMSS-1 fixes nitrogen in ammonium-deficient medium, it
      also produces larger fractionation, but it occurs at faster csSRRs than in the
      ammonium-replete control cultures. The energy and reducing power required for
      nitrogen fixation may be responsible for the reverse trend between S-isotope
      fractionation and csSRR in this case. Iron deficiency and nitrogen fixation by
      sulfate-reducing microbes may lead to the large observed S-isotope effects in
      some euxinic basins and various anoxic sediments.

PMID- 23001668
TI  - Evolution of the capsular operon of Streptococcus iniae in response to
      vaccination.
AB  - Streptococcus iniae causes severe septicemia and meningitis in farmed fish and is
      also occasionally zoonotic. Vaccination against S. iniae is problematic, with
      frequent breakdown of protection in vaccinated fish. The major protective
      antigens in S. iniae are the polysaccharides of the capsule, which are essential
      for virulence. Capsular biosynthesis is driven and regulated by a 21-kb operon
      comprising up to 20 genes. In a long-term study, we have sequenced the capsular
      operon of strains that have been used in autogenous vaccines across Australia and
      compared it with the capsular operon sequences of strains subsequently isolated
      from infected vaccinated fish. Intriguingly, strains isolated from vaccinated
      fish that subsequently become infected have coding mutations that are confined to
      a limited number of genes in the cps operon, with the remainder of the genes in
      the operon remaining stable. Mutations in strains in diseased vaccinated fish
      occur in key genes in the capsular operon that are associated with polysaccharide
      configuration (cpsG) and with regulation of biosynthesis (cpsD and cpsE). This,
      along with high ratios of nonsynonymous to synonymous mutations within the cps
      genes, suggests that immune response directed predominantly against capsular
      polysaccharide may be driving evolution in a very specific set of genes in the
      operon. From these data, it may be possible to design a simple polyvalent vaccine
      with a greater operational life span than the current monovalent killed
      bacterins.

PMID- 23001669
TI  - Fate of Bacillus thuringiensis subsp. israelensis in the field: evidence for
      spore recycling and differential persistence of toxins in leaf litter.
AB  - Bacillus thuringiensis subsp. israelensis is a bioinsecticide increasingly used
      worldwide for mosquito control. Despite its apparent low level of persistence in
      the field due to the rapid loss of its insecticidal activity, an increasing
      number of studies suggested that the recycling of B. thuringiensis subsp.
      israelensis can occur under specific, unknown conditions. Decaying leaf litters
      sampled in mosquito breeding sites in the French Rhone-Alpes region several
      months after a treatment were shown to exhibit a high level of larval toxicity
      and contained large amounts of spores. In the present article, we show that the
      high concentration of toxins found in these litters is consistent with spore
      recycling in the field, which gave rise to the production of new crystal toxins.
      Furthermore, in these toxic leaf litter samples, Cry4Aa and Cry4Ba toxins became
      the major toxins instead of Cyt1Aa in the commercial mixture. In a microcosm
      experiment performed in the laboratory, we also demonstrated that the toxins,
      when added in their crystal form to nontoxic leaf litter, exhibited patterns of
      differential persistence consistent with the proportions of toxins observed in
      the field-collected toxic leaf litter samples (Cry4 > Cry11 > Cyt). These results
      give strong evidence that B. thuringiensis subsp. israelensis recycled in
      specific breeding sites containing leaf litters, and one would be justified in
      asking whether mosquitoes can become resistant when exposed to field-persistent
      B. thuringiensis subsp. israelensis for several generations.

PMID- 23001670
TI  - Detection and tracking of a novel genetically tagged biological simulant in the
      environment.
AB  - A variant of Bacillus thuringiensis subsp. kurstaki containing a single, stable
      copy of a uniquely amplifiable DNA oligomer integrated into the genome for
      tracking the fate of biological agents in the environment was developed. The use
      of genetically tagged spores overcomes the ambiguity of discerning the test
      material from pre-existing environmental microflora or from previously released
      background material. In this study, we demonstrate the utility of the genetically
      "barcoded" simulant in a controlled indoor setting and in an outdoor release. In
      an ambient breeze tunnel test, spores deposited on tiles were reaerosolized and
      detected by real-time PCR at distances of 30 m from the point of deposition. Real
      time PCR signals were inversely correlated with distance from the seeded tiles.
      An outdoor release of powdered spore simulant at Aberdeen Proving Ground,
      Edgewood, MD, was monitored from a distance by a light detection and ranging
      (LIDAR) laser. Over a 2-week period, an array of air sampling units collected
      samples were analyzed for the presence of viable spores and using barcode
      specific real-time PCR assays. Barcoded B. thuringiensis subsp. kurstaki spores
      were unambiguously identified on the day of the release, and viable material was
      recovered in a pattern consistent with the cloud track predicted by prevailing
      winds and by data tracks provided by the LIDAR system. Finally, the real-time PCR
      assays successfully differentiated barcoded B. thuringiensis subsp. kurstaki
      spores from wild-type spores under field conditions.

PMID- 23001671
TI  - Breaking the silence: protein stabilization uncovers silenced biosynthetic gene
      clusters in the fungus Aspergillus nidulans.
AB  - The genomes of filamentous fungi comprise numerous putative gene clusters coding
      for the biosynthesis of chemically and structurally diverse secondary metabolites
      (SMs), which are rarely expressed under laboratory conditions. Previous
      approaches to activate these genes were based primarily on artificially targeting
      the cellular protein synthesis apparatus. Here, we applied an alternative
      approach of genetically impairing the protein degradation apparatus of the model
      fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5
      deneddylase subunit of the COP9 signalosome. This defect in protein degradation
      results in the activation of a previously silenced gene cluster comprising a
      polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2
      oxopropyl)benzaldehyde (DHMBA). The csnE/CSN5 gene is highly conserved in fungi,
      and therefore, the deletion is a feasible approach for the identification of new
      SMs.

PMID- 23001672
TI  - Electrosynthesis of commodity chemicals by an autotrophic microbial community.
AB  - A microbial community originating from brewery waste produced methane, acetate,
      and hydrogen when selected on a granular graphite cathode poised at -590 mV
      versus the standard hydrogen electrode (SHE) with CO(2) as the only carbon
      source. This is the first report on the simultaneous electrosynthesis of these
      commodity chemicals and the first description of electroacetogenesis by a
      microbial community. Deep sequencing of the active community 16S rRNA revealed a
      dynamic microbial community composed of an invariant Archaea population of
      Methanobacterium spp. and a shifting Bacteria population. Acetobacterium spp.
      were the most abundant Bacteria on the cathode when acetogenesis dominated.
      Methane was generally the dominant product with rates increasing from <1 to 7 mM
      day(-1) (per cathode liquid volume) and was concomitantly produced with acetate
      and hydrogen. Acetogenesis increased to >4 mM day(-1) (accumulated to 28.5 mM
      over 12 days), and methanogenesis ceased following the addition of 2
      bromoethanesulfonic acid. Traces of hydrogen accumulated during initial selection
      and subsequently accelerated to >11 mM day(-1) (versus 0.045 mM day(-1) abiotic
      production). The hypothesis of electrosynthetic biocatalysis occurring at the
      microbe-electrode interface was supported by a catalytic wave (midpoint potential
      of -460 mV versus SHE) in cyclic voltammetry scans of the biocathode, the lack of
      redox active components in the medium, and the generation of comparatively high
      amounts of products (even after medium exchange). In addition, the volumetric
      production rates of these three commodity chemicals are marked improvements for
      electrosynthesis, advancing the process toward economic feasibility.

PMID- 23001673
TI  - Prevalence and diversity of viruses in the entomopathogenic fungus Beauveria
      bassiana.
AB  - Viruses have been discovered in numerous fungal species, but unlike most known
      animal or plant viruses, they are rarely associated with deleterious effects on
      their hosts. The knowledge about viruses among entomopathogenic fungi is very
      limited, although their existence is suspected because of the presence of virus
      like double-stranded RNA (dsRNA) in isolates of several species. Beauveria
      bassiana is one of the most-studied species of entomopathogenic fungi; it has a
      cosmopolitan distribution and is used as a biological control agent against
      invertebrates in agriculture. We analyzed a collection of 73 isolates obtained at
      different locations and from different habitats in Spain and Portugal, searching
      for dsRNA elements indicative of viral infections. The results revealed that the
      prevalence of viral infections is high; 54.8% of the isolates contained dsRNA
      elements with viral characteristics. The dsRNA electropherotypes of infected
      isolates indicated that virus diversity was high in the collection analyzed and
      that mixed virus infections occurred in fungal isolates. However, a hybridization
      experiment indicated that dsRNA bands that are similar in size do not always have
      similar sequences. Particular virus species or dsRNA profiles were not associated
      with locations or types of habitats, probably because of the ubiquity and
      efficient dispersion of this fungus as an airborne species. The sequence of one
      of the most common dsRNA elements corresponded to the 5.2-kbp genome of a
      previously undescribed member of the Totiviridae family, termed B. bassiana RNA
      virus 1 (BbRV1).

PMID- 23001674
TI  - Detection and Identification of Salmonella enterica, Escherichia coli, and
      Shigella spp. via PCR-electrospray ionization mass spectrometry: isolate testing
      and analysis of food samples.
AB  - An assay to identify the common food-borne pathogens Salmonella, Escherichia
      coli, Shigella, and Listeria monocytogenes was developed in collaboration with
      Ibis Biosciences (a division of Abbott Molecular) for the Plex-ID biosensor
      system, a platform that uses electrospray ionization mass spectroscopy (ESI-MS)
      to detect the base composition of short PCR amplicons. The new food-borne
      pathogen (FBP) plate has been experimentally designed using four gene segments
      for a total of eight amplicon targets. Initial work built a DNA base count
      database that contains more than 140 Salmonella enterica, 139 E. coli, 11
      Shigella, and 36 Listeria patterns and 18 other Enterobacteriaceae organisms.
      This assay was tested to determine the scope of the assay's ability to detect and
      differentiate the enteric pathogens and to improve the reference database
      associated with the assay. More than 800 bacterial isolates of S. enterica, E.
      coli, and Shigella species were analyzed. Overall, 100% of S. enterica, 99% of E.
      coli, and 73% of Shigella spp. were detected using this assay. The assay was also
      able to identify 30% of the S. enterica serovars to the serovar level. To further
      characterize the assay, spiked food matrices and food samples collected during
      regulatory field work were also studied. While analysis of preenrichment media
      was inconsistent, identification of S. enterica from selective enrichment media
      resulted in serovar-level identifications for 8 of 10 regulatory samples. The
      results of this study suggest that this high-throughput method may be useful in
      clinical and regulatory laboratories testing for these pathogens.

PMID- 23001676
TI  - Biotin-binding proteins in the defense of mushrooms against predators and
      parasites.
AB  - Tamavidins are fungal biotin-binding proteins (BBPs) displaying antifungal
      activity against phytopathogens. Here we show high toxicity of tamavidins toward
      nematodes, insects, and amoebae. As these organisms represent important phyla of
      fungal predators and parasites, we propose that BBPs are part of the chemical
      defense system of fungi.

PMID- 23001677
TI  - Identification and distribution of high-abundance proteins in the octopus spring
      microbial mat community.
AB  - A shotgun metaproteomics approach was employed to identify proteins in a hot
      spring microbial mat community. We identified 202 proteins encompassing 19 known
      functions from 12 known phyla. Importantly, we identified two key enzymes
      involved in the 3-hydroxypropionate CO(2) fixation pathway in uncultivated
      Roseiflexus spp., which are known photoheterotrophs.

PMID- 23001675
TI  - Phylogenetic analysis and polyphasic characterization of Clavibacter
      michiganensis strains isolated from tomato seeds reveal that nonpathogenic
      strains are distinct from C. michiganensis subsp. michiganensis.
AB  - The genus Clavibacter comprises one species and five subspecies of plant
      pathogenic bacteria, four of which are classified as quarantine organisms due to
      the high economic threat they pose. Clavibacter michiganensis subsp.
      michiganensis is one of the most important pathogens of tomato, but the
      recommended diagnostic tools are not satisfactory due to false-negative and/or 
      positive results. To provide a robust analysis of the genetic relatedness among a
      worldwide collection of C. michiganensis subsp. michiganensis strains, relatives
      (strains from the four other C. michiganensis subspecies), and nonpathogenic
      Clavibacter-like strains isolated from tomato, we performed multilocus sequence
      based analysis and typing (MLSA and MLST) based on six housekeeping genes (atpD,
      dnaK, gyrB, ppK, recA, and rpoB). We compared this "framework" with phenotypic
      and genotypic characteristics such as pathogenicity on tomato, reaction to two
      antisera by immunofluorescence and to five PCR identification tests, and the
      presence of four genes encoding the main C. michiganensis subsp. michiganensis
      pathogenicity determinants. We showed that C. michiganensis subsp. michiganensis
      is monophyletic and is distinct from its closest taxonomic neighbors. The
      nonpathogenic Clavibacter-like strains were identified as C. michiganensis using
      16S rRNA gene sequencing. These strains, while cross-reacting with C.
      michiganensis subsp. michiganensis identification tools, are phylogenetically
      distinct from the pathogenic strains but belong to the C. michiganensis clade. C.
      michiganensis subsp. michiganensis clonal complexes linked strains from highly
      diverse geographical origins and also strains isolated over long periods of time
      in the same location. This illustrates the importance of seed transmission in the
      worldwide dispersion of this pathogen and its survival and adaptation abilities
      in a new environment once introduced.

PMID- 23001678
TI  - Biosynthesis of cis,cis-muconic acid and its aromatic precursors, catechol and
      protocatechuic acid, from renewable feedstocks by Saccharomyces cerevisiae.
AB  - Adipic acid is a high-value compound used primarily as a precursor for the
      synthesis of nylon, coatings, and plastics. Today it is produced mainly in
      chemical processes from petrochemicals like benzene. Because of the strong
      environmental impact of the production processes and the dependence on fossil
      resources, biotechnological production processes would provide an interesting
      alternative. Here we describe the first engineered Saccharomyces cerevisiae
      strain expressing a heterologous biosynthetic pathway converting the intermediate
      3-dehydroshikimate of the aromatic amino acid biosynthesis pathway via
      protocatechuic acid and catechol into cis,cis-muconic acid, which can be
      chemically dehydrogenated to adipic acid. The pathway consists of three
      heterologous microbial enzymes, 3-dehydroshikimate dehydratase, protocatechuic
      acid decarboxylase composed of three different subunits, and catechol 1,2
      dioxygenase. For each heterologous reaction step, we analyzed several potential
      candidates for their expression and activity in yeast to compose a functional
      cis,cis-muconic acid synthesis pathway. Carbon flow into the heterologous pathway
      was optimized by increasing the flux through selected steps of the common
      aromatic amino acid biosynthesis pathway and by blocking the conversion of 3
      dehydroshikimate into shikimate. The recombinant yeast cells finally produced
      about 1.56 mg/liter cis,cis-muconic acid.

PMID- 23001679
TI  - Air-lift internal loop biofilm reactor for realized simultaneous nitrification
      and denitrification.
AB  - Simultaneous nitrification and denitrification (SND) was realized by means of a
      novel air-lift internal loop biofilm reactor, in which aeration was set in middle
      of the reactor. During operation, the aeration was adjusted to get appropriate
      dissolve oxygen (DO) in bulk solution and let aerobic and anoxic zone coexist in
      one reactor. When aeration was at 0.6 and 0.2 L/min, corresponding to DO of 5.8
      and 2.5 mg/L in bulk solution, ammonia nitrogen removal percentage reached about
      80 and 90 %, but total nitrogen removal percentage was lower than 25 %. While the
      aeration was reduced to 0.1 L/min, aerobic and anoxic zones existed
      simultaneously in one reactor to get 75 % of ammonia nitrogen and 50 % of total
      nitrogen removal percentage. Biofilms were, respectively, taken from aerobic and
      anoxic zone to verify their function of nitrification and denitrification in two
      flasks, in which ammonia nitrogen was transferred into nitrate completely by
      aerobic biofilm, and nitrate was removed more than 80 % by anoxic biofilm.
      Microelectrode was used to measure the DO distribution inside biofilms in anoxic
      zone corresponding to different aerations. When aeration was at 0.6 and 0.2
      L/min, DO inside biofilm was more than 1.5 mg/L, but the DO inside biofilm
      decreased to anoxic status with depth of biofilm increasing corresponding to
      aeration of 0.1 L/min. The experimental results indicated that SND could be
      realized because of simultaneous existence of aerobic and anoxic biofilms in one
      reactor.

PMID- 23001680
TI  - Human apo-lactoferrin as a physiological mimetic of hypoxia stabilizes hypoxia
      inducible factor-1 alpha.
AB  - Apo-form of human lactoferrin (LF) is a potent iron chelator, this feature being
      similar to the iron-binding properties of a synthetic chelator desferoxamine
      (DFO). The latter stabilizes the principal adaptive transcriptional hypoxia
      inducible factor-1 alpha (HIF-1alpha). Since DFO is known as a pharmacological
      mimetic of hypoxia it was decided to test whether apo-LF is able to perform as
      such. Mice either injected intraperitoneally or given per os apo-LF displayed HIF
      1alpha in liver, lungs, heart, brain, spleen and kidneys, as judged by results of
      Western blotting. Similar administration of iron-saturated LF (75 mg/kg) did not
      bring forth such effect. Synthesis of erythropoietin and ceruloplasmin became
      increased in the first case, which is explained by the respective genes being
      targets for HIF-1alpha. Apo-LF, but not Fe-LF, injected intraperitoneally to
      hypoxia low-resistant mice 24 h before animals were subjected to normobaric
      hypoxia with hypercapnia caused a significant increase of life-time by 40 %. The
      results obtained show that, like DFO, apo-LF performs as a normoxic mimetic of
      hypoxia, capable of stabilizing HIF-1alpha. Protective features of LF and DFO and
      their pharmacological properties involving HIF-1alpha are discussed.

PMID- 23001681
TI  - Systematic review and meta-analysis of duplex ultrasonography, contrast-enhanced
      ultrasonography or computed tomography for surveillance after endovascular
      aneurysm repair.
AB  - BACKGROUND: Previous analyses suggested that duplex ultrasonography (DUS)
      detected endoleaks after endovascular aneurysm repair (EVAR) with insufficient
      sensitivity; they did not specifically examine types 1 and 3 endoleak, which, if
      untreated, may lead to aneurysm-related death. In light of changes to clinical
      practice, the diagnostic accuracy of DUS and contrast-enhanced ultrasonography
      (CEUS) for types 1 and 3 endoleak required focused reappraisal. METHODS: Studies
      comparing DUS or CEUS with computed tomography (CT) for endoleak detection were
      identified. CT was taken as the standard in bivariable meta-analysis. RESULTS:
      Twenty-five studies (3975 paired scans) compared DUS with CT for all endoleaks.
      The pooled sensitivity was 0.74 (95 per cent confidence interval 0.62 to 0.83)
      and the pooled specificity was 0.94 (0.90 to 0.97). Thirteen studies (2650 paired
      scans) reported detection of types 1 and 3 endoleak by DUS; the pooled
      sensitivity of DUS was 0.83 (0.40 to 0.97) and the pooled specificity was 1.00
      (0.97 to 1.00). Eleven studies (961 paired scans) compared CEUS with CT for all
      endoleaks. The pooled sensitivity of CEUS was 0.96 (0.85 to 0.99) and the pooled
      specificity was 0.85 (0.76 to 0.92). Eight studies (887 paired scans) reported
      detection of types 1 and 3 endoleak by CEUS. The pooled sensitivity of CEUS was
      0.99 (0.25 to 1.00) and the pooled specificity was 1.00 (0.98 to 1.00).
      CONCLUSION: Both CEUS and DUS were specific for detection of types 1 and 3
      endoleak. Estimates of their sensitivity were uncertain but there was no evidence
      of a clinically important difference. DUS detects types 1 and 3 endoleak with
      sufficient accuracy for surveillance after EVAR.

PMID- 23001682
TI  - Uneven spatial distribution of surface EMG: what does it mean?
AB  - The aim of this work is to show how changes in surface electromyographic activity
      (sEMG) during a repetitive, non-constant force contraction can be detected and
      interpreted on the basis of the amplitude distribution provided by high-density
      sEMG techniques. Twelve healthy male subjects performed isometric shoulder
      elevations, repeating five times a force ramp profile up to 25 % of the maximal
      voluntary contraction (MVC). A 64-electrode matrix was used to detect sEMG from
      the trapezius muscle. The sEMG amplitude distribution was obtained for the force
      levels in the range 5-25 % MVC with steps of 5 % MVC. The effect of force level,
      subject, electrode position and ramp repetition on the sEMG amplitude
      distribution was tested. The sEMG amplitude was significantly smaller in the
      columns of the electrode grid over the tendons (repeated measures ANOVA, p <
      0.01). The barycentre of the distribution of sEMG amplitude was subject-specific
      (Kruskal-Wallis test, p < 0.01), and shifted caudally with the increase of force
      levels and cranially with the repetition of the motor task (both p < 0.01,
      repeated measures ANOVA). The results are discussed in terms of motor unit
      recruitment in different muscle sub-portions. It is concluded that the sEMG
      amplitude distribution obtained by multichannel techniques provides useful
      information in the study of muscle activity, and that changes in the spatial
      distribution of the recruited motor units during a force varying isometric
      contraction might partially explain the variability observed in the activation
      pattern of the upper trapezius muscle.

PMID- 23001683
TI  - Changes in surface EMG assessed by discrete wavelet transform during maximal
      isometric voluntary contractions following supramaximal cycling.
AB  - To better understand characteristics of neuromuscular fatigue in supramaximal
      cycling exercise, this study examined changes in surface electromyography (sEMG)
      frequency during maximal voluntary isometric contractions (MVC) following a 30-s
      Wingate anaerobic test (WAnT) using discrete wavelet transform (DWT). The changes
      in sEMG were also compared between DWT and mean frequency (MNF) obtained by fast
      Fourier transform (FFT). 17 healthy men performed a WAnT with a 7.5 % of body
      mass load. Knee extensor MVC torque was measured before and 1, 3, 6, 9, 12 and 15
      min following WAnT, and sEMG was recorded from vastus lateralis muscle during the
      torque measures. sEMG was analysed for (RMS), MNF by FFT and frequency domains of
      DWT (divided into six domains). MVC torque decreased 21-23 % at 3-15 min, RMS
      increased 26-34 % at 1-15 min, and MNF decreased 8-10 % from baseline (76.3 +/-
      3.2 Hz) at 1-3 min post-cycling (P < 0.05). The DWT frequency domains showed that
      the changes lasted longer than MNF such that the intensity increased at 12 and 15
      min for domain 2 (125-250 Hz), all time points for domain 3 (62.5-125 Hz), and 1
      6 min for domains 4 (31.2-62.5 Hz) and 5 (15.6-31.2 Hz). The magnitude of
      increase in the intensity at 1 min post-exercise (45-60 %) was largest for
      domains 3 and 5 (P < 0.05). A significant correlation was evident only between
      the magnitude of changes in the domain 5 and MNF (r = -0.56). It is concluded
      that DWT provides information on neuromuscular fatigue that is not detected by
      MNF derived from FFT.

PMID- 23001685
TI  - Celecoxib does not affect the release of hyaluronic acid in end stage
      osteoarthritic joints.
AB  - OBJECTIVES: Non-steroidal anti-inflammatory drugs play a major role in the
      management of osteoarthritis (OA). However, it remains unknown whether these
      drugs affect cartilage and synovial metabolism in osteoarthritic joints. The aim
      of this study was to evaluate the effects of a selective cyclooxygenase (COX)-2
      inhibitor, celecoxib, on synovial fluids and tissues in severely osteoarthritic
      knees. METHODS: Patients were randomized into three groups and medicated two
      weeks prior to total knee arthroplasty with celecoxib, diclofenac sodium, or no
      medication (control). We checked for the presence of matrix metalloproteinase-3
      (MMP-3), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      and hyaluronic acid (HA) in the synovial fluids of all three groups. RESULTS: MMP
      3 significantly decreased in the celecoxib-treated patients (p = 0.0031). On the
      other hand, there were no significant differences among the three groups in their
      TNF-alpha and IL-1beta levels. HA in the joint fluid was significantly increased
      in the diclofenac-treated group, while HA was not changed in the celecoxib
      treated patients. CONCLUSIONS: Our study suggests that celecoxib did not affect
      the level of HA in the joint fluid in the knee in severe OA, in contrast to the
      effect of the dual COX inhibitor.

PMID- 23001684
TI  - Natural selection on marine carnivores elaborated a diverse family of classical
      MHC class I genes exhibiting haplotypic gene content variation and allelic
      polymorphism.
AB  - Pinnipeds, marine carnivores, diverged from terrestrial carnivores ~45 million
      years ago, before their adaptation to marine environments. This lifestyle change
      exposed pinnipeds to different microbiota and pathogens, with probable impact on
      their MHC class I genes. Investigating this question, genomic sequences were
      determined for 71 MHC class I variants: 27 from harbor seal and 44 from gray
      seal. These variants form three MHC class I gene lineages, one comprising a
      pseudogene. The second, a candidate nonclassical MHC class I gene, comprises a
      nonpolymorphic transcribed gene related to dog DLA-79 and giant panda Aime-1906.
      The third is the diversity lineage, which includes 62 of the 71 seal MHC class I
      variants. All are transcribed, and they minimally represent six harbor and 12
      gray seal MHC class I genes. Besides species-specific differences in gene number,
      seal MHC class I haplotypes exhibit gene content variation and allelic
      polymorphism. Patterns of sequence variation, and of positions for positively
      selected sites, indicate the diversity lineage genes are the seals' classical MHC
      class I genes. Evidence that expansion of diversity lineage genes began before
      gray and harbor seals diverged is the presence in both species of two distinctive
      sublineages of diversity lineage genes. Pointing to further expansion following
      the divergence are the presence of species-specific genes and greater MHC class I
      diversity in gray seals than harbor seals. The elaboration of a complex variable
      family of classical MHC class I genes in pinnipeds contrasts with the single,
      highly polymorphic classical MHC class I gene of dog and giant panda, terrestrial
      carnivores.

PMID- 23001687
TI  - Functional roles of transient receptor potential melastatin 8 (TRPM8) channels in
      the cold stress-induced detrusor overactivity pathways in conscious rats.
AB  - AIMS: We determined if transient receptor potential melastatin 8 (TRPM8) channels
      are involved in the detrusor overactivity induced by menthol, or exposure to low
      temperature (LT). METHODS: Two days prior to cystometric investigation, the
      bladders of 10-week-old Sprague-Dawley rats were cannulated to measure bladder
      pressure. After a 20 min baseline cystometry period, the TRPM8 channel
      antagonist, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1
      carboxamide (BCTC), or vehicle, was administered through a jugular vein catheter
      (n = 6). A 90% menthol solution was sprayed onto bare leg skin once every 5 min
      for 20 min, and then cystometric measurements were repeated. After a 30-min
      recovery period, the rats were intravenously administered 0.1 umol/kg BCTC. Five
      minutes later, they were again sprayed and cystometry recorded. In separate
      experiments, cannulated rats were intravenously administered 0.001, 0.01, or 0.1
      umol/kg BCTC (n = 6 each dose). Five minutes later, they were exposed to LT (4 +/
      2 degrees C) for 20 min of cystometry. RESULTS: Menthol spray decreased voiding
      interval, micturition volume, and bladder capacity in the BCTC-free rats. However
      after BCTC administration, these effects were prevented. Exposure to LT elicited
      detrusor overactivity that caused decreased voiding interval, micturition volume,
      and bladder capacity. However, at 0.01 and 0.1 umol/kg, BCTC inhibited this cold
      stress-induced detrusor overactivity. CONCLUSIONS: Since the TRPM8 channel
      agonist, BCTC, inhibited detrusor overactivity in rats sprayed with the TRPM8
      channel agonist, menthol, and the drug also inhibited cold stress-induced
      detrusor overactivity, we conclude that TRPM8 channels mediate, at least
      partially, detrusor overactivity elicited by exposure to LT.

PMID- 23001688
TI  - Direct acyl substitution of carboxylic acids: a chemoselective O- to N-acyl
      migration in the traceless Staudinger ligation.
AB  - A chlorophosphite-modified, Staudinger-like acylation of azides involving a
      highly chemoselective, direct nucleophilic acyl substitution of carboxylic acids
      is described. The reaction provides the corresponding amides with analytical
      purity in 32-97% yield after a simple aqueous workup without the need for a pre
      activation step. The use of chlorophosphites as dual carboxylic acid-azide
      activating agents enables the formation of acyl C-N bonds in the presence of a
      wide range of nucleophilic and electrophilic functional groups, including amines,
      alcohols, amides, aldehydes, and ketones. The coupling of carboxylic acids and
      azides for the formation of alkyl amides, sulfonyl amides, lactams, and
      dipeptides is described.

PMID- 23001689
TI  - A community-based intervention to prevent obesity beginning at birth among
      American Indian children: study design and rationale for the PTOTS study.
AB  - Eating and physical activity behaviors associated with adult obesity have early
      antecedents, yet few studies have focused on obesity prevention interventions
      targeting very young children. Efforts to prevent obesity beginning at birth seem
      particularly important in populations at risk for early-onset obesity. National
      estimates indicate that American Indian (AI) children have higher rates of
      overweight and obesity than children of other races/ethnicities. The Prevention
      of Toddler Obesity and Teeth Health Study (PTOTS) is a community-partnered
      randomized controlled trial designed to prevent obesity beginning at birth in AI
      children. PTOTS was developed to test the effectiveness of a multi-component
      intervention designed to: promote breastfeeding, reduce sugar-sweetened beverage
      consumption, appropriately time the introduction of healthy solid foods, and
      counsel parents to reduce sedentary lifestyles in their children. A birth cohort
      of 577 children from five AI tribes is randomized by tribe to either the
      intervention (three tribes) or the comparison condition (two tribes). The
      strengths and weaknesses of PTOTS include a focus on a critical growth phase,
      placement in the community, and intervention at many levels, using a variety of
      approaches.

PMID- 23001690
TI  - The N-terminus of vaccinia virus host range protein C7L is essential for
      function.
AB  - Vaccinia virus (VACV), a member of the Poxviridae family of large double-stranded
      DNA viruses, is being used as a smallpox vaccine as well as an expression vector
      for immunization against other infectious diseases and cancer. The host range of
      wild type VACV is very broad among mammalian cells. C7L is a host range gene
      identified in VACV and is well conserved in mammalian poxviruses except for
      parapoxviruses and molluscum contagiosum virus. The molecular mechanisms by which
      the C7L gene exerts host range function are not well understood. The C7L protein
      does not have any known conserved domains or show sequence similarity to cellular
      proteins or viral proteins other than the C7L homologs in mammalian poxviruses.
      We generated recombinant vaccinia viruses carrying deletion mutants of the C7L
      gene using NYVAC as a parental strain and found that the N-terminus is essential
      for host range function of C7L, which is consistent with a previous report that
      showed that homology among C7L homologs are greater near the N-terminus than the
      C-terminus.

PMID- 23001692
TI  - Mycoplasma pneumoniae extract induces an IL-17-associated inflammatory reaction
      in murine lung: implication for mycoplasmal pneumonia.
AB  - Mycoplasma pneumoniae (Mp) may cause immune cell reactions as pivotal aspects of
      this clinically common respiratory pathogen. Our aim is to determine if Mp
      extract induces a cellular immune response associated with interleukin (IL)-17,
      leading to lung inflammation and lung injury. BALB/c mice were immunized with Mp
      extract intraperitoneally followed by its intratracheal administration, to mimic
      repeated Mp infection found in humans (repeated inoculation, RI group). Those
      with a single inoculation were compared as single inoculation group (SI group).
      Analysis of bronchoalveolar lavage fluid (BALF) demonstrated that keratinocyte
      derived cytokine, tumor necrosis factor-alpha, and IL-6 were produced and peaked
      on days 0.5 or 1, followed by IL-17 on day 2. Levels of these mediators in BALF
      were higher in RI group than SI group (P < 0.05). Further, significantly more
      neutrophils were recruited to the lungs of the RI group (P < 0.05). These
      observations suggest that IL-17 is involved in the prolonged induction of
      neutrophils in mice treated with Mp extract.

PMID- 23001693
TI  - Protective effects of polydeoxyribonucleotides on cartilage degradation in
      experimental cultures.
AB  - The capacity of cartilage self-regeneration is considered to be limited. Joint
      injuries often evolve in the development of chronic wounds on the cartilage
      surface. Such lesions are associated with articular cartilage degeneration and
      osteoarthritis. Re-establishing a correct micro/macro-environment into damaged
      joints could stop or prevent the degenerative processes. This study investigated
      the effect of polydeoxyribonucleotides (PDRNs) on cartilage degradation in vitro
      and on cartilage extracted cells. The activities of matrix metalloproteinases 2
      and 9 were measured in PDRN-treated cells and in controls at days 0 and 30 of
      culture. Human nasal cartilage explants were cultured, and the degree of
      proteoglycan degradation was assessed by measuring the amount of
      glycosaminoglycans released into the culture medium. The PDRN properties compared
      with controls were tested on cartilage tissues to evaluate deposition of
      extracellular matrix. Chondrocytes treated with PDRNs showed a physiological
      deposition of extracellular matrix (aggrecan and type II collagen: Western blot,
      IFA, fluorescence activated cell sorting, Alcian blue and safranin O staining).
      PDRNs were able to inhibit proteoglycan degradation in cartilage explants. The
      activities of matrix metalloproteinases 2 and 9 were reduced in all PDRN-treated
      samples. Our results indicate that PDRNs are suitable for a long-term cultivation
      of in vitro cartilage and have therapeutic effects on chondrocytes by protecting
      cartilage.

PMID- 23001694
TI  - Prevalence and correlates of exceeding the labeled maximum dose of acetaminophen
      among adults in a U.S.-based internet survey.
AB  - PURPOSE: Acetaminophen is a commonly used analgesic; excessive doses can lead to
      liver damage. We sought to determine the proportion of acetaminophen users
      exceeding the recommended maximum daily dose of 4 g and identify correlates of
      such behavior. METHODS: U.S. adults were recruited from an internet panel in
      summer 2010, oversampling past 30-day acetaminophen users. Among 47 738 starting
      the study, 5649 completed all phases; individuals with low education were
      underrepresented. Subjects completed a 7-day daily diary online, reporting intake
      of acetaminophen products selected from a comprehensive list; total daily dose
      was computed from product names. An exit survey elicited: attitudes/knowledge
      related to product ingredients, label reading, dosing behavior; demographics,
      medical history, general physical, and mental health status. Unconditional
      logistic regression identified variables independently associated with use
      exceeding 4 g. RESULTS: Among 3618 acetaminophen users, 163 took >4 g on >=1 day
      (4.5%); the median dose was 5.5 g; 26 took >8 g (0.7%). >4-g users were
      characterized by chronic pain, poor physical status, and heavy use of medical
      care. Knowledge of ingredients and recommended OTC doses for all products taken
      was inversely associated with >4-g use (multivariable odds ratios [ORs] = 0.5
      0.6), as was the attitude to start with the lowest dose (OR = 0.6). The attitude
      that users could choose their own dose was positively associated (OR = 1.3).
      CONCLUSIONS: The results estimate the proportion of acetaminophen users exceeding
      4 g in a group of U.S. adults, identify potentially modifiable attitudes and
      knowledge associated with such use, and characterize subpopulations at higher
      risk.

PMID- 23001695
TI  - Abstracts of the 63rd Irish Cardiac Society Annual Scientific Meeting. October 12
      13, 2012. Maynooth, County Kildare, Ireland.

PMID- 23001696
TI  - Complete genome sequence of arracacha mottle virus.
AB  - Arracacha mottle virus (AMoV) is the only potyvirus reported to infect arracacha
      (Arracacia xanthorrhiza) in Brazil. Here, the complete genome sequence of an
      isolate of AMoV was determined to be 9,630 nucleotides in length, excluding the
      3' poly-A tail, and encoding a polyprotein of 3,135 amino acids and a putative
      P3N-PIPO protein. Its genomic organization is typical of a member of the genus
      Potyvirus, containing all conserved motifs. Its full genome sequence shared 56.2
      % nucleotide identity with sunflower chlorotic mottle virus and verbena virus Y,
      the most closely related viruses.

PMID- 23001691
TI  - Determinants of inter-specific variation in basal metabolic rate.
AB  - Basal metabolic rate (BMR) is the rate of metabolism of a resting,
      postabsorptive, non-reproductive, adult bird or mammal, measured during the
      inactive circadian phase at a thermoneutral temperature. BMR is one of the most
      widely measured physiological traits, and data are available for over 1,200
      species. With data available for such a wide range of species, BMR is a benchmark
      measurement in ecological and evolutionary physiology, and is often used as a
      reference against which other levels of metabolism are compared. Implicit in such
      comparisons is the assumption that BMR is invariant for a given species and that
      it therefore represents a stable point of comparison. However, BMR shows
      substantial variation between individuals, populations and species. Investigation
      of the ultimate (evolutionary) explanations for these differences remains an
      active area of inquiry, and explanation of size-related trends remains a
      contentious area. Whereas explanations for the scaling of BMR are generally
      mechanistic and claim ties to the first principles of chemistry and physics,
      investigations of mass-independent variation typically take an evolutionary
      perspective and have demonstrated that BMR is ultimately linked with a range of
      extrinsic variables including diet, habitat temperature, and net primary
      productivity. Here we review explanations for size-related and mass-independent
      variation in the BMR of animals, and suggest ways that the various explanations
      can be evaluated and integrated.

PMID- 23001698
TI  - Analysis of the electronic circular dichroism spectrum of (-)
      [9](2,5)Pyridinophane.
AB  - The results of a combined experimental and theoretical study of the electronic
      circular dichroism spectrum of (-)-[9] (2,5)Pyridinophane are presented. The
      features observed in the measured spectrum in the 180-350 nm wavelength region
      are reproduced by a series of calculations carried out within a density
      functional time-dependent approach, coupled with a vibronic analysis allowing
      rationalizing unambiguously the chiral response of the molecule.

PMID- 23001697
TI  - Complete genome sequence analysis of Japanese encephalitis virus isolated from a
      horse in India.
AB  - The complete genome of the Japanese encephalitis virus (JEV) strain
      JEV/eq/India/H225/2009(H225), isolated from an infected horse in India, was
      sequenced and compared to previously published JEV genomes. H225 genome was
      10,977-nucleotides long, comprising a single ORF of 10,299-nucleotides, a 5'-UTR
      of 95 nucleotides and a 3'-UTR of 582 nucleotides. The H225 genome showed high
      levels of sequence identity with 47 fully sequenced JEV genomes, ranging from
      99.3 % to 75.5 % for nucleotides and 99.2 % to 91.5 % for amino acid sequences.
      Phylogenetic analysis of the full-length sequence indicated that the H225 strain
      belongs to genotype III and is closely related to the Indian JEV strain Vellore
      P20778. A comparison of amino acids associated with neurovirulence in the E
      proteins and non-structural proteins of known virulent and attenuated JEV strains
      suggested H225 to be a highly virulent strain. This is the first report of whole
      genome sequencing of a genotype III JEV genome isolated from equines.

PMID- 23001699
TI  - Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: A
      nested case-control study within the Korean Multicenter Cancer Cohort.
AB  - This study was conducted to evaluate the relevance of the soluble form of c-Met
      protein, a truncated form of the c-Met membrane receptor involved in the CagA
      pathway, as a potential biomarker for gastric cancer. Among 290 gastric cancer
      case-control sets selected from the Korean Multicenter Cancer Cohort, the plasma
      concentrations of soluble c-Met protein were measured with enzyme-linked
      immunosorbent assays. Using analysis of variance and covariance models with age,
      sex, smoking, Helicobacter pylori infection, and CagA seropositivity, the mean
      concentrations of soluble c-Met protein between cases and controls were compared.
      To evaluate the association between gastric cancer and a c-Met protein level,
      odds ratios and 95% confidence intervals were estimated using conditional
      logistic regression models. Interactions between CagA-related genes and the
      soluble c-Met protein concentration were also investigated. The overall median
      plasma concentration of soluble c-Met among cases was significantly lower than
      those of controls (1.390 vs. 1.610 ng/mL, p < 0.0001). Closer to the onset of
      gastric cancer, the soluble c-Met protein level decreased linearly in a time
      dependent manner (p for trend = 0.0002). The combined effects between the CagA
      related genes and the soluble c-Met protein concentration significantly
      intensified risks for gastric cancer. Restricted analyses including cases that
      had been diagnosed within 1 year after entering the cohort had a fair degree of
      ability (area under the receiver operating characteristic curve of 0.73-0.77) to
      discriminate gastric cancer cases from normal controls. Our findings demonstrate
      the potential of the soluble form of c-Met protein as a novel biomarker for
      gastric cancer. The beneficial effects of a high soluble c-Met concentration in
      human plasma are strongly supported.

PMID- 23001701
TI  - Coordinating properties of uridine 5'-monophosphate with selected Ln(3+) ions in
      ionic micellar media.
AB  - Coordinating properties of uridine 5'-monophosphate (UMP) towards trivalent La,
      Pr, Nd, Sm, Eu and Gd ions in presence of cationic and anionic micelles have been
      investigated by potentiometric pH-titration and spectroscopic methods. Stability
      constants of the 2:1 complexes have been determined and the change in free
      energy, enthalpy and entropy associated with the complexation are also
      calculated. Nd(III) complexes isolated from aqueous and aqueous-micellar media do
      not show any significant structural difference. Formation of Ln(III) complexes in
      all cases completes below pH 7.5 showing that UMP best interacts with Ln(3+) ions
      at the physiological pH range 7.3-7.5. The nucleobase is not involved in the
      complexation and the metal ion coordination of UMP is through the phosphate
      moiety only. Coordinating tendency of UMP with lanthanides, Nd(III) ion in
      particular, at different pH is also discussed. Luminescent properties of Eu(III)
      complex and its decay lifetime are also presented. This information may prove
      helpful regarding the use of lanthanides as biological probes for
      calcium/magnesium ions.

PMID- 23001702
TI  - Two-step synthesis of stable dioxadicarbaporphyrins from bis(3-indenyl)methane.

PMID- 23001703
TI  - Hepatitis C cure after 6 months of telaprevir-based therapy in an HIV-infected
      man.

PMID- 23001704
TI  - Lack of a clinically significant drug-drug interaction in healthy volunteers
      between the hepatitis C virus protease inhibitor boceprevir and the HIV integrase
      inhibitor raltegravir.
AB  - BACKGROUND: Patients coinfected with human immunodeficiency virus (HIV) and
      hepatitis C virus (HCV) are likely to use both HIV and HCV treatment. Drug-drug
      interactions have been demonstrated between boceprevir, an HCV protease
      inhibitor, and frequently prescribed antiretroviral drugs, such as efavirenz and
      boosted HIV protease inhibitors. Concomitant administration of boceprevir with
      these drugs should be avoided. This study was designed to investigate the absence
      of a drug-drug interaction between boceprevir and raltegravir, an HIV integrase
      inhibitor. METHODS: This was an open-label, randomized, 2-period, crossover phase
      1 trial in 24 healthy volunteers. All subjects were randomly assigned to receive
      boceprevir 800 mg every 8 hours for 9 days plus a single dose of raltegravir 400
      mg on day 10 followed by a washout period and a single dose of raltegravir 400 mg
      on day 38, or the same medication in reverse order. Blood samples for
      pharmacokinetics were collected and pharmacokinetic parameters were calculated.
      RESULTS: The geometric mean (GM) of raltegravir area under the concentration-time
      curve (AUC)(0-12h) and maximum plasma concentration (C(max)) for raltegravir +
      boceprevir vs raltegravir alone were 4.27 (95% confidence interval [CI], 3.22
      5.66) vs 4.04 (95% CI, 3.09-5.28) mg * hour/L and 1.06 (95% CI, .76-1.49) vs 0.93
      (95% CI, .70-1.23) mg/L, respectively. GM ratio estimates of raltegravir AUC(0
      12h) and C(max) for raltegravir + boceprevir vs raltegravir alone were 1.04 (90%
      CI, .88-1.22) and 1.11 (90% CI, .91-1.36), respectively. The GM of boceprevir
      AUC(0-8h), C(max), and C(8h) were 5.45 (95% CI, 5.11-5.81) mg * hour/L, 1.88 (95%
      CI, 1.72-2.06) mg/L, and 0.09 (95% CI, .07-.11) mg/L, respectively. These data
      are comparable to those from historical controls. CONCLUSIONS: Due to the absence
      of a clinically significant drug interaction, raltegravir can be recommended for
      combined HIV/HCV treatment including boceprevir. CLINICAL TRIALS REGISTRATION:
      NCT01288417.

PMID- 23001705
TI  - Biomarkers of parathyroid carcinoma.
AB  - The diagnosis of parathyroid carcinoma can be challenging, and adjuvant therapies
      such as radiotherapy and chemotherapy are not particularly beneficial in the
      management of this disease, creating a challenge when dealing with unresectable
      recurrent and metastatic malignancy. We investigated the expression profile of
      biomarkers that represent potential markers of malignancy or targets for novel
      therapies in this disease. We constructed a tissue microarray of parathyroid
      carcinomas from 10 patients as well as parathyroid adenomas from 25 patients and
      stained the slides for 34 proteins involved in angiogenesis (platelet-derived
      growth factor receptor (PDGFR)-alpha, PDGFR-beta, vascular endothelial growth
      factor receptor-2 (VEGFR-2), and epidermal growth factor receptor (EGFR)),
      inflammation (cyclooxygenase (COX)-1 and COX-2), cell adhesion (matrix
      metalloproteinase (MMP)-1, CD9, and keratin 7), cell cycle (Cdc2p34, cyclin D1,
      retinoblastoma (Rb), p27, p21, parafibromin, Bmi-1, 14-3-3sigma, and p53), and
      apoptosis (Bcl-2a, Mcl-1, Bcl-xL, and glutathione-S-transferase-isoenzyme pi (Gst
      pi)) along with some markers of the sonic hedgehog (Smo, SHH, Gli-1, Gli-2, Gli
      3, and patched), mTOR (AKT, mammalian target of rapamycin (mTOR), and Forkhead
      box O (FoxO)-1), and WNT (Wisp-1, Wisp-2, and beta-catenin) signal transduction
      pathways. Protein expression was determined using computerized image analysis
      software (Spectrum Plus(c), Aperio). Bcl-2a, parafibromin, Rb, and p27 were
      significantly decreased to variable degrees in all parathyroid carcinomas. COX
      1/2, CD9, MMP-1, FoxO-1, VEGFR-2, PDGFR-alpha/beta, Gst-pi, Gli-1, Gli-2, Gli-3,
      and patched were expressed in the majority of benign and malignant tumor cells.
      These results indicate that the use of a panel that includes Bcl-2a,
      parafibromin, Rb, and p27 may be helpful in the assessment of atypical
      parathyroid neoplasms. Although the majority of other markers studied are also
      expressed in both benign and malignant parathyroid neoplasms, we have identified
      several potentially important target proteins related to angiogenesis and cell
      proliferation along with COX-1/2, Gst-pi and members of sonic hedgehog pathway
      that may be therapeutic targets in parathyroid carcinoma. While these results are
      preliminary, a successful outcome of a clinical trial directed against these
      novel targets would provide much needed systemic adjuvant treatment for patients
      with metastatic parathyroid carcinoma.

PMID- 23001706
TI  - Neuropsychiatric symptoms in Alzheimer's disease and vascular dementia.
AB  - Neuropsychiatric symptoms (NPSs) have a large impact on the quality of life of
      patients with dementia. A few studies have compared neuropsychiatric disturbances
      between dementia subtypes, but the results were conflicting. In the present
      study, we investigated whether the prevalence of NPSs differs between Alzheimer's
      disease (AD) and vascular dementia (VaD). The merit of our study is that we used
      clinical as well as histopathological information to differentiate between
      dementia subtypes. This retrospective descriptive study comprised 80 brains
      obtained from donors to the Netherlands Brain Bank between 1984 and 2010. These
      donors were diagnosed postmortem with AD (n = 40) or VaD (n = 40). We assessed
      the presence of NPSs by reviewing the information found in the patients' medical
      files. The most prevalent symptom in the sample as a whole was agitation (45
      cases, 57.0%), followed by depression (33, 41.2%) and anxiety (28, 35.4%). Our
      study tried to contribute to the discussion by including, for the first time in
      the literature, a sample of AD and VaD patients with neuropathologically
      confirmed diagnoses. Since no significant differences were found between AD and
      VaD patients, we suggest that the prevalence of NPSs cannot be predicted from the
      diagnosis of AD or VaD.

PMID- 23001707
TI  - Apathy syndrome in Alzheimer's disease epidemiology: prevalence, incidence,
      persistence, and risk and mortality factors.
AB  - The objective of this paper was to assess the prevalence, incidence, persistence,
      and risk and mortality factors for Apathy Syndrome in Alzheimer's disease (ASAD)
      in a clinical sample. This was a cohort study of 491 patients with probable
      Alzheimer's disease (AD). The Cambridge Examination for Mental Disorders of the
      Elderly (CAMDEX), the Neuropsychiatric Inventory (NPI), the Rapid Disability
      Rating Scale (RDRS-2), and the Zarit Burden Interview (ZBI) were administered,
      and all patients were reevaluated after 12 months. Baseline ASAD diagnosis was
      made using specific diagnostic criteria. ASAD prevalence and incidence/year were
      21.0% and 10.6%, respectively. After one year, ASAD persisted in 61.2% of
      patients. At baseline, patients with ASAD scored lower on the CAMCOG and higher
      on the Blessed, RDRS-2, and ZBI. Antipsychotic use was the only risk factor for
      ASAD (RR = 3.159; 95% CI: 1.247-8.003). ASAD was related to an increased
      functional disability, but no relationship with cognitive impairment or increased
      caregiver burden was detected. Finally, ASAD was associated with an increased
      risk of mortality (HR = 1.987; 95% CI: 1.145-3.450; p = 0.014). ASAD suggests a
      more severe AD clinical profile, with poorer functional progression and increased
      mortality risk. Antipsychotic use seems to be the only risk factor for ASAD.

PMID- 23001708
TI  - Brain cholinergic markers and Tau phosphorylation are altered in experimental
      type 1 diabetes: normalization by electroacupuncture.
AB  - Diabetes often correlates with tau phosphorylation and the development of
      Alzheimer's disease. Both are associated with brain cholinergic dysfunction that
      could benefit from nerve growth factor (NGF)-based therapies. Electroacupuncture
      (EA) improves brain NGF availability and action. Here we assessed the variations
      of NGF and tau phosphorylation in the cortex and hippocampus, as well as the
      expression of choline acetyltransferase in the basal forebrain following diabetes
      induction and EA in adult rats. We found that EA counteracts diabetes-associated
      tau hyperphosphorylation and decreases in NGF and choline acetyltransferase,
      suggesting a possible beneficial effect of EA on brain cholinergic system in
      diabetes.

PMID- 23001709
TI  - Altered parietal-motor connections in Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is characterized by altered functional cortico-cortical
      connectivity likely due to loss of afferent and efferent connections between
      different cortical areas. Here we explored parieto-frontal functional
      connectivity in 15 AD patients and 12 healthy control subjects by means of
      bifocal transcranial magnetic stimulation (TMS). Conditioning stimuli were
      applied over the right posterior parietal cortex (PPC) at different intensities
      (90% and 110% of resting motor threshold, RMT). Motor evoked potentials (MEPs)
      were then recorded from the ipsilateral primary motor cortex at different
      interstimulus intervals (ISIs) ranging between 2 and 15 ms. Results showed that
      in healthy subjects, a conditioning TMS pulse applied over the ipsilateral PPC at
      90%, but not at 110%, of RMT intensity was able to increase the excitability of
      the right M1. This functional interaction peaked at ISI = 6 ms. Conversely, in AD
      patients the facilitatory pattern of parieto-motor connections was evident only
      when TMS was delivered at an intensity of 110% of RMT with a peak at ISI = 8 ms.
      Moreover in AD patients, treatment with cholinesterase inhibitors did not induce
      any significant modification in the strength of the connection. In subsequent
      analyses, we found that, in AD patients, the effects induced by PPC conditioning
      at 110% RMT correlated with neuropsychological measures of episodic memory and
      executive functions, implying that patients with better cognitive performance had
      less impaired connectivity. Our findings reveal that parieto-frontal cortico
      cortical functional connectivity is altered in AD patients, providing further
      evidence for a disconnection-based interpretation of AD symptoms.

PMID- 23001710
TI  - Rapid decline in episodic memory in healthy older adults with high amyloid-beta.
AB  - High levels of amyloid-beta (Abeta) have been associated with greater rates of
      decline in episodic memory over 18 months in healthy older adults. Serial
      assessments over shorter time intervals may facilitate earlier detection of Abeta
      related memory decline in healthy older adults. In forty-four healthy older
      adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Rate of
      Change Sub-Study, we compared rates of change in cognition over six months in
      healthy older adults with high and low levels of Abeta. High Abeta was associated
      with greater decline in episodic memory measures over 6 months in healthy older
      adults.

PMID- 23001711
TI  - Elevated MARK2-dependent phosphorylation of Tau in Alzheimer's disease.
AB  - The appearance of neurofibrillary tangles (NFT), one of the major hallmarks of
      Alzheimer's disease (AD), is most likely caused by inappropriate phosphorylation
      and/or dephosphorylation of tau, eventually leading to the accumulation of NFTs.
      Enhanced phosphorylation of tau on Ser(262) is detected early in the course of
      the disease and may have a role in the formation of tangles. Several kinases such
      as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium
      calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on
      Ser(262) in vitro. In this study, we took advantage of the in situ proximity
      ligation assay to investigate the role of MARK2, one of the four MARK isoforms,
      in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at
      Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau.
      Staurosporine, a protein kinase inhibitor, significantly reduced the interaction
      between MARK2 and tau, and also phosphorylation of tau at Ser(262). Furthermore,
      we observed elevated interactions between MARK2 and tau in post-mortem human AD
      brains, compared to samples from non-demented elderly controls. Our results from
      transfected cells demonstrate a specific interaction between MARK2 and tau, as
      well as MARK2-dependent phosphorylation of tau at Ser(262). Furthermore, the
      elevated interactions between MARK2 and tau in AD brain sections suggests that
      MARK2 may play an important role in early phosphorylation of tau in AD, possibly
      qualifying as a therapeutic target for intervention to prevent disease
      progression.

PMID- 23001712
TI  - Potential immunotargets for Alzheimer's disease treatment strategies.
AB  - Alzheimer's disease (AD) exerts a profound burden on public health worldwide. AD
      etiology is unknown, and research to understand its underlying pathology has
      produced agents for the management of symptoms, but not a cure for the disease.
      Most AD drugs were developed in response to research implicating fibrillar
      amyloid-beta (Abeta) in AD neuropathology but result in only modest short-term
      improvements in cognitive function, so there is agreement that additional targets
      need to be investigated. Evidence has implicated the immune system in AD and
      immunotherapy as a potential approach to AD treatment. Accumulation of microglia
      and astrocytes has been observed around Abeta deposits and several reports
      implicate inflammatory mediators in AD pathology. Importantly, Abeta deposition
      has been found in the brains of AD patients and in aged people without dementia,
      but signs of neuroinflammation are found only in AD patients and not in normal
      aged individuals. Animal models suggest a complex role for immunomodulators in
      AD, namely, these mechanisms are likely to promote the same pathogenic processes
      that gave rise to them. To date, clinical trials with anti-inflammatories and
      other immunoregulators have not been successful, but available data strongly
      favor immunomodulation as a promising disease intervention strategy. This article
      reviews data that implicate various immunomodulators in AD and considers their
      potential application in the development of novel AD therapeutics. Currently, a
      deeper understanding of nervous-immune interactions during normal aging and at
      all stages of AD is needed. Continued research in AD inflammatory and
      immunoregulatory processes will increase both our understanding of disease
      mechanisms and the likelihood of discovering new therapeutic targets for AD.

PMID- 23001713
TI  - CC chemokine receptor 5 polymorphism in Italian patients with giant cell
      arteritis.
AB  - OBJECTIVES: To evaluate the potential role of CC chemokine receptor 5
      (CCR5)Delta32 polymorphism in the susceptibility to giant cell arteritis (GCA) in
      a cohort of Italian patients. METHODS: 176 consecutive Italian patients with
      biopsy-proven GCA and 180 healthy age- and sex-matched blood donors were
      molecularly genotyped for the CCR5Delta32 polymorphism. RESULTS: No statistically
      significant difference in the Delta32CCR5 allele frequency between GCA patients
      (5.1 %) and controls (2.8 %) was observed (p = 0.109). Carriers of the
      CCR5Delta32 allele (Delta32/Delta32 + CCR5/Delta32) were similarly represented in
      the two groups. CONCLUSIONS: Our results do not support a role for the
      CCR5Delta32 polymorphism in determining susceptibility to GCA.

PMID- 23001715
TI  - Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as
      a screening method for the prevention of colorectal cancer.
AB  - BACKGROUND: Colorectal cancer is a significant cause of death. Removal of
      precancerous adenomas, and early detection and treatment of cancer, has been
      shown to reduce the risk of death. The aim of this review and meta-analysis was
      to determine whether flexible sigmoidoscopy (FS) is an effective population
      screening method for reducing mortality from colorectal cancer. METHODS: MEDLINE
      (1946 to December 2012) and Embase (1980-2012, week 15) were searched for
      randomized clinical trials in which FS was used to screen non-symptomatic adults
      from a general population, and FS was compared with either no screening or any
      other alternative screening methods. Meta-analysis was carried out using a random
      effects Mantel-Haenzsel model. RESULTS: Twenty-four papers met the inclusion
      criteria, reporting results from 14 trials. Uptake of FS was usually lower than
      that for stool-based tests, although FS was more effective at detecting advanced
      adenoma and carcinoma. FS reduced the incidence of colorectal cancer after
      screening, and long-term mortality from colorectal cancer, compared with no
      screening in a selected population. Compared with stool-based tests in a general
      population, FS was associated with fewer interval cancers. CONCLUSION: FS is
      efficacious at reducing colorectal cancer mortality compared with no screening.
      It is more effective at detecting advanced adenoma and carcinoma than stool-based
      tests. FS may be compromised by poorer uptake. Introduction of FS as a screening
      method should be done on a pilot basis in populations in which it is not
      currently used, and close attention should be paid to maximizing uptake. The
      relative risk of adverse events with FS compared with stool-based tests should be
      quantified, and its real-world effectiveness evaluated against the most effective
      stool-based tests.

PMID- 23001714
TI  - In young post-myocardial infarction male patients elevated plasminogen activator
      inhibitor-1 correlates with insulin resistance and endothelial dysfunction.
AB  - Classical and nonclassical risk factors contribute to the development of
      myocardial infarction (MI) in young patients. The aim of the present study was to
      find out whether insulin resistance and impaired fibrinolysis, with increased
      plasminogen activator inhibitor (PAI-1), are present in young male post-MI
      patients, and their relation to additional markers of cardiovascular risk such as
      endothelial dysfunction (ED) and intima-media thickness (IMT). Forty-one male
      patients (on average 44 years old) in the stable phase after MI were recruited,
      with 25 healthy males who did not differ from patients regarding age as controls.
      Body mass index (BMI) and waist-to-hip ratio were measured and insulin resistance
      was calculated. Several coagulation/fibrinolytic parameters and inflammation
      markers were measured. ED was estimated by ultrasound measurement of the flow
      mediated dilatation (FMD) of the brachial artery, and IMT was measured on the
      common carotid artery. BMI was increased in post-MI patients in comparison with
      healthy controls. Compared with the control group, in post-MI patients PAI-1
      antigen (13.8 +/- 10.6 vs 9.1 +/- 7.6 ng/ml, P = 0.042), PAI-1 activity (14.8 +/-
      10.8 vs 9.0 +/- 8.0 IU/ml, P = 0.015), and fibrinogen were significantly
      elevated. In patients increased PAI-1, antigen and activity were both
      significantly positively related to insulin resistance. We found an important
      negative relation between PAI-1 antigen and FMD (r = -0.32, P = 0.04) and between
      PAI-1 activity and FMD (r = -0.39, P = 0.01). Our results suggest that PAI-1 can
      be a link between obesity, insulin resistance, and MI in young patients. It is
      thus concluded that impaired fibrinolysis with increased PAI-1 may be an
      important nonclassical risk factor for MI, particularly in young males with
      increased BMI and insulin resistance. 

PMID- 23001716
TI  - Inter-observer agreement for spectral- and time-domain optical coherence
      tomography image grading: a prospective study.
AB  - The purpose of this study was to compare inter-observer agreement of StratusTM
      OCT versus SpectralisTM OCT image grading in patients with neovascular age
      related macular degeneration (AMD). Thirty eyes with neovascular AMD were
      examined with StratusTM OCT and SpectralisTM OCT. Four different scan protocols
      were used for imaging. Three observers graded the images for the presence of
      various pathologies. Inter-observer agreement between OCT models was assessed by
      calculating intra-class correlation coefficients (ICC). In StratusTM OCT highest
      interobserver agreement was found for subretinal fluid (ICC: 0.79), and in
      SpectralisTM OCT for intraretinal cysts (IRC) (ICC: 0.93). SpectralisTM OCT
      showed superior interobserver agreement for IRC and epiretinal membranes (ERM)
      (ICC(StratusTM): for IRC 0.61; for ERM 0.56; ICC(SpectralisTM): for IRC 0.93; for
      ERM 0.84). Increased image resolution of SpectralisTM OCT did improve the inter
      observer agreement for grading intraretinal cysts and epiretinal membranes but
      not for other retinal changes.

PMID- 23001717
TI  - A United States forensic sample for the Gudjonsson Suggestibility Scales.
AB  - The Gudjonsson Suggestibility Scales (GSS) is a valuable test to use as part of a
      comprehensive assessment of psychological and interrogative factors relevant to a
      defendant's vulnerability to giving a false or involuntary confession. One
      limitation of the test is that the manual only provides information for samples
      from Iceland and Great Britain. This report describes the results of 334
      individuals in the United States, who were administered the tests as part of an
      evaluation to assess confession-related issues in a forensic context (i.e.,
      capacity to waive Miranda rights or vulnerability in providing a false or
      involuntary confession). This forensic sample includes both juveniles and adults.
      Results are consistent with Gudjonsson's British and Icelandic samples, in which
      the Yield 1 score is more affected by intellectual and cognitive variables, but
      Shift and, to a lesser extent, Yield 2 scores are more related to emotional and
      personality characteristics.

PMID- 23001718
TI  - The impact of dietary long-chain polyunsaturated fatty acids on respiratory
      illness in infants and children.
AB  - Increasing evidence suggests that intake of long-chain polyunsaturated fatty
      acids (LCPUFA), especially omega-3 LCPUFA, improves respiratory health early in
      life. This review summarizes publications from 2009 through July 2012 that
      evaluated effects of fish, fish oil or LCPUFA intake during pregnancy, lactation,
      and early postnatal years on allergic and infectious respiratory illnesses.
      Studies during pregnancy found inconsistent effects in offspring: two showed no
      effects and three showed protective effects of omega-3 LCPUFA on respiratory
      illnesses or atopic dermatitis. Two studies found that infants fed breast milk
      with higher omega-3 LCPUFA had reduced allergic manifestations. Earlier
      introduction of fish improved respiratory health or reduced allergy in four
      studies. Three randomized controlled trials showed that providing LCPUFA during
      infancy or childhood reduced allergy and/or respiratory illness while one found
      no effect. Potential explanations for the variability among studies and possible
      mechanisms of action for LCPUFA in allergy and respiratory disease are discussed.

PMID- 23001719
TI  - Homophobic name-calling among secondary school students and its implications for
      mental health.
AB  - Although homophobic verbal victimization has been associated with negative mental
      health outcomes, little actually is known about its general prevalence and
      relationship to mental health among adolescents. In addition, the relationship of
      homophobic name-calling to mental health in gender non-conforming adolescents is
      not well understood. This study examined the relationship between homophobic
      verbal victimization and mental health in adolescents, accounting for their
      sexual orientation and level of gender non-conformity. Survey data was collected
      from 513 adolescents (ages 11-17) who attended eight schools in and around
      Amsterdam, the Netherlands; 56.7 % of the participating adolescents were female
      and 11.1 % reported same-sex attractions. As hypothesized, male adolescents and
      those with same-sex attractions were more likely to report victimization from
      homophobic name-calling than were their female and non-same-sex attracted peers.
      Contrary to expectations, homophobic name-calling was not independently
      associated with psychological distress after controlling for gender, sexual
      attractions, gender non-conformity, and other negative treatment by peers. The
      hypothesis that homophobic name-calling would be more strongly associated with
      psychological distress in male, same-sex attracted, and gender non-conforming
      adolescents was also not supported. The results suggest that same-sex attracted
      and gender non-conforming youth are particularly vulnerable to homophobic name
      calling, in the Netherlands as in other contexts, but also that other forms of
      peer victimization may be more strongly related to mental health.

PMID- 23001720
TI  - Virus nomenclature below the species level: a standardized nomenclature for
      natural variants of viruses assigned to the family Filoviridae.

PMID- 23001721
TI  - Molecular characterisation of rabies virus strains in the Republic of Macedonia.
AB  - Rabies, a worldwide zoonosis, remains a public-health concern despite oral
      wildlife vaccination in Europe. After a ten-year break, Macedonia reported eight
      rabies cases in 2011-2012. Two countries (Serbia and Bulgaria) bordering
      Macedonia are reporting cases in domestic and wild animals. This report describes
      the genetic characterisation of eight isolates from Macedonia compared with
      representative samples from neighbouring countries. All of the isolates tested
      belong to the Eastern European group, with a high degree of nucleotide sequence
      identity in the nucleoprotein gene. The close genetic relationship between
      isolates from the three bordering countries suggests that wildlife is responsible
      for rabies movements in the region.

PMID- 23001722
TI  - Epigenetic silencing of WNT5A in Epstein-Barr virus-associated gastric carcinoma.
AB  - Epstein-Barr virus (EBV) is responsible for the development of multiple tumors,
      including EBV-associated gastric carcinoma (EBVaGC), but little is known about
      its mechanisms in EBVaGC. WNT5A expression and promoter methylation were measured
      in 5 EBV-positive and 15 EBV-negative GC cell lines. The methylation status of 23
      EBV-positive and 25 EBV-negative paired tumor/normal tissue samples was also
      examined. EBV-positive GC had no or very low expression of WNT5A but a high level
      of methylation in the promoter region. In contrast, EBV-negative GC had higher
      WNT5A expression and a lower level of promoter methylation. The reduced WNT5A
      expression could be restored by treatment with Aza, a methyltransferase
      inhibitor. Increased expression of WNT5A in vitro inhibited beta-catentin
      expression in EBVaGC cells (SNU719). These results suggest that hypermethylation
      of WNT5A induced by EBV may contribute to the development of EBVaGC. Ectopic
      introduction of WNT5A may have preventive/therapeutic potential for tumors with
      silenced WNT5A.

PMID- 23001723
TI  - Derepression of c-Fos caused by microRNA-139 down-regulation contributes to the
      metastasis of human hepatocellular carcinoma.
AB  - This study investigates whether the anti-metastasis effect of microRNA-139 (miR
      139) on hepatocellular carcinoma (HCC) is mediated through regulating c-fos
      expression. The expression levels of miR-139 and c-fos in human HCC cell sublines
      with high (MHCC97H) and low (MHCC97L) spontaneous metastatic potentials were
      quantified using QPCR or Western blot. miR-139 mimics was transfected into
      MHCC97H cells to overexpress miR-139, and miR-139 inhibitor was transfected into
      MHCC97L cells to down-express miR-139. The effect of overexpression or down
      expression of miR-139 on c-fos expression of MHCC97H and MHCC97L cells was
      evaluated using QPCR and Western blot. The 3' untranslated region segments of FOS
      containing the miR-139 binding sites were amplified by PCR, and the luciferase
      activity in the transfected cells was assayed. In comparison with the expression
      level of miR-139 in MHCC97L cells, the expression level in MHCC97H cells was
      significantly decreased, whereas c-Fos was significantly up-regulated in MHCC97H.
      The overexpression of miR-139 significantly inhibited the expression of c-fos in
      MHCC97H cells, and the down-expression of miR-139 significantly promoted the
      expression of c-fos in MHCC97L cells. miR-139 suppressed the luciferase activity
      of the pGL-FOS by approximately 40% compared with the negative control. In vitro
      cell migration analysis demonstrated that depletion of c-fos or overexpression of
      miR-139 in MHCC97H cells reduced cell migration, whereas overexpression of c-fos
      or depletion of miR-139 in MHCC97L cells increased cell migration. Thus, we got
      the conclusion that miR-139 expression is down-regulated in human HCC cell
      sublines with high spontaneous metastatic potentials (MHCC97H). Derepression of c
      Fos caused by miR-139 down-regulation contributes to the metastasis of HCC.

PMID- 23001724
TI  - Efficient calculation of ROA tensors with analytical gradients and fragmentation.
AB  - We present the results of calculations of Raman optical activity spectra of
      sizable systems from optical tensors of the fragments, the tensors calculated by
      an analytic approach at the time-dependent Hartree-Fock level of theory. The
      analytic approach permits large basis sets which, together with the limited
      geometrical extent of the fragments, obviates the need for the use of London-type
      orbitals. The implementation of the analytical gradient approach is formulated in
      the atomic orbital basis by using the elements of the density matrix as
      variational parameters. This makes the approach directly applicable to linear
      scaling methods. We do not solve the response equations for the geometrical
      distortions of the nuclei but determine instead the second-order perturbed
      densities with respect to the electromagnetic field perturbations. The number of
      perturbed density matrices that needs to be determined is thus independent of the
      number of nuclei, making the approach applicable to fragments with many nuclei
      and with good quality basis sets. Compared to numerical differentiation schemes,
      the analytical approach is about 10 times faster even for moderately sized
      molecules.

PMID- 23001725
TI  - Experimental and DFT evidence for the fractional non-innocence of a beta
      diketonate ligand.
AB  - New compounds [Ru(pap)(2)(L)](ClO(4)), [Ru(pap)(L)(2)], and [Ru(acac)(2)(L)] (pap
      = 2-phenylazopyridine, L(-) = 9-oxidophenalenone, acac(-) = 2,4-pentanedionate)
      have been prepared and studied regarding their electron-transfer behavior, both
      experimentally and by using DFT calculations. [Ru(pap)(2)(L)](ClO(4)) and
      [Ru(acac)(2)(L)] were characterized by crystal-structure analysis.
      Spectroelectrochemistry (EPR, UV/Vis/NIR), in conjunction with cyclic
      voltammetry, showed a wide range of about 2 V for the potential of the Ru(III/II)
      couple, which was in agreement with the very different characteristics of the
      strongly pi-accepting pap ligand and the sigma-donating acac(-) ligand. At the
      rather high potential of +1.35 V versus SCE, the oxidation of L(-) into L(?)
      could be deduced from the near-IR absorption of [Ru(III)(pap)(L(?))(L(-))](2+).
      Other intense long-wavelength transitions, including LMCT (L(-) -> Ru(III)) and
      LL/CT (pap(?-) -> L(-)) processes, were confirmed by TD-DFT results. DFT
      calculations and EPR data for the paramagnetic intermediates allowed us to assess
      the spin densities, which revealed two cases with considerable contributions from
      L-radical-involving forms, that is, [Ru(III)(pap(0))(2)(L(-))](2+) <->
      [Ru(II)(pap(0))(2)(L(?))](2+) and [Ru(III)(pap(0))(L(-))(2)](+) <->
      [Ru(II)(pap(0))(L(?))(L(-))](+). Calculations of electrogenerated complex
      [Ru(II)(pap(?-))(pap(0))(L(-))] displayed considerable negative spin density (
      0.188) at the bridging metal.

PMID- 23001726
TI  - The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in
      human gastric cancer cells.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers
      of target genes and play critical roles during carcinogenesis. The selective
      cyclooxygenase-2 (COX-2) inhibitor celecoxib has been highlighted as a potential
      drug for treatment of gastrointestinal tumors. The aim of this study was to
      investigate the role of miRNAs in gastric carcinogenesis and the feasibility of a
      new therapeutic approach for gastric cancer. miRNA expression profiles were
      examined in 53 gastric tumors including gastric adenomas (atypical epithelia),
      early gastric cancers and advanced gastric cancers and in gastric cancer cells
      treated with celecoxib. miRNA microarray analysis revealed that miR-29c was
      significantly downregulated in gastric cancer tissues relative to nontumor
      gastric mucosae. miR-29c was significantly activated by celecoxib in gastric
      cancer cells. Downregulation of miR-29c was associated with progression of
      gastric cancer and was more prominent in advanced gastric cancers than in gastric
      adenomas and early gastric cancer. In addition, expression of the oncogene Mcl-1,
      a target of miR-29c, was significantly increased in gastric cancer tissues
      relative to nontumor gastric mucosae. Activation of miR-29c by celecoxib induced
      suppression of Mcl-1 and apoptosis in gastric cancer cells. These results suggest
      that downregulation of the tumor suppressor miR-29c plays critical roles in the
      progression of gastric cancer. Selective COX-2 inhibitors may have clinical
      promise for the treatment of gastric cancer via restoration of miR-29c.

PMID- 23001728
TI  - Equine pericardium as a biological covering for the treatment of diabetic foot
      wounds: a prospective study.
AB  - BACKGROUND: Diabetic foot wounds remain a significant health-care issue. Healing
      these wounds in a timely manner is of paramount importance because the duration
      of ulceration correlates with increased rates of infection and amputation,
      costing billions of dollars yearly. Collagen-based matrices have been used as
      wound covers and have been shown to improve and expedite healing. We present our
      experience with equine pericardium biomatrix for the treatment of neuropathic
      foot wounds. METHODS: Thirty-four patients with 37 diabetic foot wounds were
      evaluated at two institutions prospectively. All of the wounds were debrided, and
      equine pericardium biomatrix was applied. Secondary dressings were changed every
      48 to 72 hours until healed or for 12 weeks after application. Healing rate at 12
      weeks, time to wound closure, and complications were evaluated. RESULTS: Twenty
      two men and 12 women (mean age, 56.9 years) were treated and evaluated. Mean and
      median wound sizes at initial treatment were 715.8 and 440 mm(2), respectively.
      The overall wound healing rate by 12 weeks was 75.7% (n =28). Mean and median
      times to wound closure were 7.2 and 7.0 weeks, respectively. No device or
      procedure-related complications were reported. CONCLUSIONS: The use of equine
      pericardium as a temporary biological scaffold is safe and effective for the
      treatment of chronic neuropathic foot wounds.

PMID- 23001727
TI  - Extended Broca's area in the functional connectome of language in adults:
      combined cortical and subcortical single-subject analysis using fMRI and DTI
      tractography.
AB  - Traditional models of the human language circuitry encompass three cortical
      areas, Broca's, Geschwind's and Wernicke's, and their connectivity through white
      matter fascicles. The neural connectivity deep to these cortical areas remains
      poorly understood, as does the macroscopic functional organization of the cortico
      subcortical language circuitry. In an effort to expand current knowledge, we
      combined functional MRI (fMRI) and diffusion tensor imaging to explore subject
      specific structural and functional macroscopic connectivity, focusing on Broca's
      area. Fascicles were studied using diffusion tensor imaging fiber tracking seeded
      from volumes placed manually within the white matter. White matter fascicles and
      fMRI-derived clusters (antonym-generation task) of positive and negative blood
      oxygen-level-dependent (BOLD) signal were co-registered with 3-D renderings of
      the brain in 12 healthy subjects. Fascicles connecting BOLD-derived clusters were
      analyzed within specific cortical areas: Broca's, with the pars triangularis, the
      pars opercularis, and the pars orbitaris; Geschwind's and Wernicke's; the
      premotor cortex, the dorsal supplementary motor area, the middle temporal gyrus,
      the dorsal prefrontal cortex and the frontopolar region. We found a functional
      connectome divisible into three systems-anterior, superior and inferior-around
      the insula, more complex than previously thought, particularly with respect to a
      new extended Broca's area. The extended Broca's area involves two new fascicles:
      the operculo-premotor fascicle comprised of well-organized U-shaped fibers that
      connect the pars opercularis with the premotor region; and (2) the triangulo
      orbitaris system comprised of intermingled U-shaped fibers that connect the pars
      triangularis with the pars orbitaris. The findings enhance our understanding of
      language function.

PMID- 23001729
TI  - Meta-analysis of flexor tendon transfer for the correction of lesser toe
      deformities.
AB  - BACKGROUND: Transfer of the flexor digitorum longus tendon is one of the surgical
      techniques described to treat lesser toe deformities. A global analysis of the
      benefits of this procedure has not been presented in the literature to date. The
      aim of this meta-analysis was to evaluate the clinical benefit of transfer of the
      flexor digitorum longus tendon regarding patient satisfaction. METHODS: A
      reviewer formally trained in meta-analysis abstraction techniques searched
      several databases to identify relevant published studies. Initially, 203
      citations were identified and evaluated for relevance. Abstract screening
      produced 112 articles to be read in their entirety, of which 17 articles studying
      515 procedures with a mean +/- SD follow-up of 54.21 +/- 20.64 months met all of
      the inclusion criteria necessary for analysis. RESULTS: Overall crude patient
      satisfaction after flexor digitorum longus tendon transfer was 86.7% (95%
      confidence interval, 81.7%-90.5%). A low grade of heterogeneity across studies (Q
      = 24.458, I(2) =34.583, P = .080) and no influence of the individual studies on
      overall estimation were found. When adjusting for higher-quality prospective
      studies, overall patient satisfaction increased to 91.8%, although it did not
      reach statistical significance. Additional a priori sources of heterogeneity
      (age, sex, studies with <3 years of follow-up, percentage of patients lost to
      follow-up, and year of publication) were evaluated by subgroup analysis and meta
      regression, but no statistical significance was found. This adjustment also
      significantly decreased heterogeneity across studies (crude Q = 24.458, high
      quality studies Q = 1.504). CONCLUSIONS: Regarding patient satisfaction, this
      comprehensive analysis provides supportive evidence of the clinical benefit of
      flexor digitorum longus tendon transfer.

PMID- 23001730
TI  - Performance of the probe-to-bone test in a population suspected of having
      osteomyelitis of the foot in diabetes.
AB  - BACKGROUND: We investigated the validity of probe-to-bone testing in the
      diagnosis of osteomyelitis in a selected subgroup of patients clinically
      suspected of having diabetic foot osteomyelitis. METHODS: Between January 1,
      2007, and December 31, 2008, inpatients and outpatients with a diabetic foot
      ulcer were prospectively evaluated, and those having a clinical diagnosis of foot
      infection and at least one of the osteomyelitis clinical suspicion criteria were
      consecutively included in this study. RESULTS: Sixty-five patients met the
      inclusion criteria and were prospectively enrolled in the study. Forty-nine
      patients (75.4%) were hospitalized, and the remaining 16 (24.6%) were followed as
      outpatients. Osteomyelitis was diagnosed in 39 patients (60.0%). Probe-to-bone
      test results were positive in 30 patients (46.1%). The positive predictive value
      for the probe-to-bone test was fairly high (87%), but the negative predictive
      value was only 62%. The sensitivity and specificity of the test were 66% and 84%,
      respectively. White blood cell counts and mean C-reactive protein levels did not
      statistically significantly differ between groups. However, erythrocyte
      sedimentation rates greater than 70 mm/h reached statistical significance between
      groups. Wound area and depth were not found to be statistically significantly
      different between groups. CONCLUSIONS: Positive probe-to-bone test results and
      erythrocyte sedimentation rates greater than 70 mm/h provide some support for the
      diagnosis of diabetic foot osteomyelitis, but it is not strong; magnetic
      resonance imaging or bone biopsy will probably be required in cases of doubt.

PMID- 23001731
TI  - First metatarsophalangeal joint motion in Homo sapiens: theoretical association
      of two-axis kinematics and specific morphometrics.
AB  - BACKGROUND: The metatarsal head and proximal phalanx exhibit considerable
      asymmetry in their shape and geometry, but there is little documentation in the
      literature regarding the prevalence of structural characteristics that occur in a
      given population. Although there is a considerable volume of in vivo and in vitro
      experiments demonstrating first metatarsal inversion around its longitudinal axis
      with dorsiflexion, little is known regarding the applicability of specific
      morphometrics to these motions. METHODS: Nine distinctive osseous characteristics
      in the metatarsal head and phalanx were selected based on their location,
      geometry, and perceived functional relationship to previous studies describing
      metatarsal motion as inversion with dorsiflexion. The prevalences of the chosen
      characteristics were determined in a cohort of 21 randomly selected skeletal
      specimens, 19 of which were provided by the anatomical preparation office at the
      University of California, San Diego, and two of which were in the possession of
      one of us (M.D.). RESULTS: The frequency of occurrence of each selected
      morphological characteristic in this sample and the relevant summary statistics
      confirm a strong association between the selected features and a conceptual two
      axis kinematic model of the metatarsophalangeal joint. CONCLUSIONS: The selected
      morphometrics are consistent with inversion of the metatarsal around its
      longitudinal axis as it dorsiflexes.

PMID- 23001732
TI  - Anatomical origin of forefoot varus malalignment.
AB  - BACKGROUND: Forefoot varus malalignment is clinically defined as a
      nonweightbearing inversion of the metatarsal heads relative to a vertical
      bisection of the calcaneus in subtalar joint neutral. Although often targeted for
      treatment with foot orthoses, the etiology of forefoot varus malalignment has
      been debated and may involve an unalterable bony torsion of the talus. METHODS:
      Forty-nine feet from 25 cadavers underwent bilateral measurement of forefoot
      alignment using adapted clinical methods, followed by dissection and measurement
      of bony talar torsion. The relationship between forefoot alignment and talar
      torsion was determined using the Pearson correlation coefficient. RESULTS: Mean
      +/- SD forefoot alignment was -0.9 degrees  +/- 9.8 degrees  (valgus) and bony
      talar torsion was 32.8 degrees  +/- 5.3 degrees  valgus. There was no association
      between forefoot alignment and talar torsion (r = 0.18; 95% confidence interval, 
      0.11 to 0.44; P = .22). CONCLUSIONS: These findings may have implications for the
      treatment of forefoot varus since they suggest that the source of forefoot varus
      malalignment may be found in an alterable soft-tissue deformity rather than in an
      unalterable bony torsion of the talus.

PMID- 23001733
TI  - Partial or total calcanectomy as an alternative to below-the-knee amputation for
      limb salvage: a systematic review.
AB  - BACKGROUND: Below-the-knee amputations are regarded as definitive treatment for
      calcaneal osteomyelitis. They may be less than desirable in patients with a
      viable midfoot and forefoot. Partial and total calcanectomies have been reported
      as an alternative for limb salvage. However, the durability of the residual limb
      is questionable. METHODS: A systematic review was undertaken to identify material
      relating to the potential for limb salvage with partial or total calcanectomy in
      ambulatory patients with calcaneal osteomyelitis. Studies eligible for inclusion
      consecutively enrolled ambulatory patients older than 18 years who underwent
      partial or total calcanectomy without adjunctive free tissue transfer for the
      treatment of calcaneal osteomyelitis and had a mean follow-up of 12 months or
      longer. RESULTS: Sixteen studies involving 100 patients (76 partial and 28 total
      calcanectomies) met all of the inclusion criteria. Weighted mean follow-up was 33
      months. Minor complications with subsequent healing occurred in less than 24% of
      patients. Most major complications were related to residual soft-tissue infection
      and osteomyelitis. Approximately 10% of patients required a major lower-extremity
      amputation. Major complications and major lower-extremity amputations occurred
      more frequently after total calcanectomy and in patients with a diagnosis of
      diabetes. Eighty-five percent of patients maintained or improved their ambulatory
      status postoperatively. Only 3% of patients decreased their ambulatory status
      postoperatively, becoming unlimited household ambulators. CONCLUSIONS: This
      systematic review provides evidence that partial or total calcanectomy is a
      viable option for limb salvage in ambulatory patients with calcaneal
      osteomyelitis.

PMID- 23001734
TI  - Weightbearing and nonweightbearing ankle dorsiflexion range of motion: are we
      measuring the same thing?
AB  - BACKGROUND: Ankle dorsiflexion range of motion has been measured in weightbearing
      and nonweightbearing conditions. The different measurement conditions may
      contribute to inconsistent conclusions regarding the role of ankle dorsiflexion
      in several pathologic conditions. The purpose of this study was to examine the
      relationship between ankle dorsiflexion range of motion as measured in
      weightbearing and nonweightbearing conditions. METHODS: We compared ankle
      dorsiflexion range of motion as measured in a weightbearing versus a
      nonweightbearing position in 43 healthy volunteers. Measurements were taken
      separately by two examiners. RESULTS: Weightbearing and nonweightbearing ankle
      dorsiflexion measurements produced significantly different results (P < .0001).
      The two measurements correlated moderately (r = 0.6 and r = 0.64 for examiners 1
      and 2, respectively; P < .001). CONCLUSIONS: Weightbearing and nonweightbearing
      ankle dorsiflexion measurements produce significantly different results and only
      a moderate correlation, suggesting that these two measurements should not be used
      interchangeably as measures of ankle dorsiflexion range of motion.

PMID- 23001735
TI  - Assessment of partial first-ray resections and their tendency to progress to
      transmetatarsal amputations: a retrospective study.
AB  - BACKGROUND: Diabetic foot infections tend to lead to amputation. Partial first
      ray resections are used to help salvage the foot and maintain bipedal ambulation.
      Losing the first metatarsophalangeal joint has biomechanical consequences that
      lead to further foot deformities and result in more proximal amputations of the
      ipsilateral limb, such as a transmetatarsal amputation. METHODS: We reviewed 48
      patients (32 male and 16 female; mean age = 62.44) who underwent 50 partial first
      ray resections between April 1, 2003, and July 31, 2009. These partial first-ray
      resections were done at various levels of the first metatarsal. We hypothesize
      that partial first-ray resections that require further bone resection will lead
      to poor biomechanics that can result in further amputation. RESULTS: We found
      that out of 50 partial first-ray resections, 24 cases required further surgical
      intervention, 12 of which were a transmetatarsal amputation (TMA) (mean time
      between partial first-ray resection and TMA = 282.08 days). Forty-eight percent
      of patients did not require further surgical intervention and were considered a
      success. CONCLUSIONS: Partial first-ray resections are not highly successful. Our
      study found a higher success rate compared to a previous study done by Cohen et
      al in 1991. Partial first-ray amputations can be a good initial procedure to
      salvage the foot and prolong a patient's bipedal ambulatory status, thereby
      lowering the patient's morbidity and mortality.

PMID- 23001736
TI  - Pilomatrixoma: an infrequently encountered lesion on the lower extremity.
AB  - We discuss the clinical presentation and treatment of pilomatrixoma as it occurs
      in the lower extremity. Although pilomatrixoma is far more common on the head,
      neck, and upper extremity, it can be found on the lower extremity. Treatment is
      aimed primarily at excision if the lesion is symptomatic or suspicious for
      malignancy. The authors present a case of a 73-year-old male who presented to the
      diabetic foot center with this condition.

PMID- 23001737
TI  - Nephrogenic systemic fibrosis in the podiatric patient.
AB  - Nephrogenic systemic fibrosis (NSF) is a severely debilitating disease that was
      first described in the literature by Cowper and colleagues in 2000. It is
      pertinent to the field of podiatry because patients with NSF first manifest
      cutaneous symptoms in the lower extremity in the form of fibrosing lesions. To
      date, these lesions have been documented only in people with moderate to severe
      kidney failure. There is speculation that gadolinium, used as a contrast agent
      for imaging, might be the inciting factor that triggers a cascade of events that
      results in the inappropriate fibrosis both in the dermis and in deeper tissues.
      Nephrogenic systemic fibrosis has been shown to cause these lesions in the lungs,
      pleura, diaphragm, myocardium, pericardium, and dura mater, the presence of which
      are typically indicative of severe progression of NSF. In cases where the lesions
      are manifest in the periarticular tissue, joint contractures and restricted range
      of motion can often result. We provide a quick synopsis of NSF, and a short case
      study that describes the authors' experience with one of their patients who
      requested a surgical consult as a result of being wheelchair-bound due to NSF's
      sequelae.

PMID- 23001738
TI  - Incidental findings of massive heel spurs in a veteran with a variant of
      psoriatic arthritis.
AB  - A middle-aged man presented for left foot diabetic ulcer care. Pedal radiographs
      were negative for signs of osteomyelitis. However, asymptomatic incidental
      osseous findings demonstrated significant plantar and posterior calcaneal
      spurring possibly consistent with diffuse idiopathic skeletal hyperostosis
      (DISH). A differential of DISH, psoriatic arthritis, Reiter's, and ankylosing
      spondylitis was developed. Subsequent spinal imaging and laboratory work-up did
      not satisfy the diagnostic criteria for DISH. This case illustrates radiographic
      changes characteristic of multiple seronegative arthropathies. On initial
      presentation a diagnosis of DISH was most likely, but with further imaging
      studies a diagnosis of a variant of psoriatic arthritis may be more correct.

PMID- 23001739
TI  - Newly approved laser systems for onychomycosis.
AB  - Laser systems are a new treatment area for onychomycosis. As of January 2012, the
      US Food and Drug Administration (FDA) has approved four laser systems for the
      "temporary increase of clear nail in onychomycosis." The FDA has approved these
      devices on the basis of "substantial equivalence" to predicate devices with
      similar technical specifications and applications. Laser therapy appears to be a
      promising alternative to traditional pharmacotherapy, but these systems have been
      tested in only limited clinical trials; therefore, it is not possible to compare
      their efficacy to the oral and topical drugs currently used in the treatment of
      onychomycosis.

PMID- 23001740
TI  - A pH-based high-throughput assay for transketolase: fingerprinting of substrate
      tolerance and quantitative kinetics.
AB  - A pH-based high-throughput assay method has been developed for the rapid and
      reliable measurement of transketolase (TK) activity. The method is based on the
      decarboxylation of lithium hydroxypyruvate (HPA) as a hydroxyacetyl donor with an
      aldehyde acceptor, using phenol red as the pH indicator. Upon release of carbon
      dioxide from HPA, the pH increase in the reaction mixture can be determined
      photometrically by the color change of the pH indicator. At low buffer
      concentration (2 mM triethanolamine, pH 7.5), the method is highly sensitive and
      allows continuous monitoring, for quantitative determination of the kinetic
      parameters. By using this method, the substrate specificities of the TK enzymes
      from Escherichia coli and Saccharomyces cerevisiae, as well as two active-site
      modified variants of the E. coli TK (D469E, H26Y) were evaluated against a panel
      of substrate analogues; specific activities and kinetic constants could be
      rapidly determined. Substrate quality indicated by assay determination was
      substantiated with novel TK applications by using achiral 3-hydroxypropanal and 4
      hydroxybutanal for preparative synthesis of chiral deoxyketose-type products.
      Determination of ee for the latter could be performed by chiral GC analysis, with
      an unambiguous correlation of the absolute configuration from rotation data. This
      pH-based assay method is broadly applicable and allows rapid, sensitive, and
      reliable screening of the substrate tolerance of known TK enzymes and variants
      obtained from directed evolution.

PMID- 23001742
TI  - Iridoschisis associated with nanophthalmos and bullous keratopathy.
AB  - Iridoschisis is a rare condition in which the iris stroma splits into anterior
      and posterior layers. Iridoschisis is associated with anterior segment
      abnormalities including keratoconus, lens subluxation and angle-closure glaucoma.
      We describe the first case in which iridoschisis has occurred in association with
      nanophthalmos. We also report the rare complication of irido-corneal touch and
      subsequent corneal decompensation. Nanophthalmos and irido-corneal touch are
      sight-threatening associations of iridoschisis and should be excluded in all
      patients with this rare condition.

PMID- 23001741
TI  - Myconanotechnology in agriculture: a perspective.
AB  - Myconanotechnology is an emerging field, where fungi can be harnessed for the
      synthesis of nanomaterials or nanostructures with desirable shape and size.
      Though myconanotechnology is in its infancy, potential applications provide
      exciting waves of transformation in agriculture and fascinate microbiologists and
      other researchers to contribute in providing incremental solutions through green
      chemistry approaches for advancing food security. In this article, we provide a
      brief overview of the research efforts on the mycogenic synthesis of
      nanoparticles with particular emphasis on mechanisms and potential applications
      in agriculture and allied sectors.

PMID- 23001743
TI  - In vivo measurement of CBF using 17O NMR signal of metabolically produced H217O
      as a perfusion tracer.
AB  - The cerebral metabolic rate of oxygen of small animals can be reliably imaged
      using the in vivo (17) O magnetic resonance approach at high field. However, a
      separate measurement is required for imaging the cerebral blood flow in the same
      animal. In this study, we demonstrate that the (17) O NMR signal of metabolically
      produced H2 (17) O in the rat brain following an (17) O2 inhalation can serve as
      a perfusion tracer and its decay rate can be used to determine the absolute
      values of cerebral blood flow across a wide range of animal conditions. This
      finding suggests that the in vivo (17) O magnetic resonance approach is capable
      of imaging both cerebral metabolic rate of oxygen and cerebral blood flow
      simultaneously and noninvasively; and it provides new utilities for studying the
      cerebral oxygen metabolism and perfusion commonly associated with brain function
      and diseases.

PMID- 23001744
TI  - Evaluation of the catalytic performance of gas-evolving electrodes using local
      electrochemical noise measurements.
AB  - Characterization of gas evolution reactions at the electrode/electrolyte boundary
      is often difficult due to the dynamic behavior of interfacial processes.
      Electrochemical noise measurements determined by scanning electrochemical
      microscopy were used to characterize Cl(2)  evolution at gas-evolving electrodes
      (GEEs). Analysis of the electrochemical noise is a powerful method to evaluate
      the efficiency of the catalyst layer at a GEE. The high sensitivity of the
      developed measurement system enabled accurate monitoring of the current
      fluctuations caused by gas-bubble detachment from the electrode surface. Fourier
      transform analysis of the obtained current responses allows extraction of the
      characteristic frequency, which is the main parameter of the macrokinetics of
      GEEs. The characteristic frequency was used as part of a methodology to evaluate
      the catalyst performance and, in particular, to estimate the fraction of the
      catalyst layer that is active during the gas evolution reaction.

PMID- 23001745
TI  - Unprocessed red and processed meats and risk of coronary artery disease and type
      2 diabetes--an updated review of the evidence.
AB  - Growing evidence suggests that effects of red meat consumption on coronary heart
      disease (CHD) and type 2 diabetes could vary depending on processing. We reviewed
      the evidence for effects of unprocessed (fresh/frozen) red and processed (using
      sodium/other preservatives) meat consumption on CHD and diabetes. In meta
      analyses of prospective cohorts, higher risk of CHD is seen with processed meat
      consumption (RR per 50 g: 1.42, 95 %CI = 1.07-1.89), but a smaller increase or no
      risk is seen with unprocessed meat consumption. Differences in sodium content
      (~400 % higher in processed meat) appear to account for about two-thirds of this
      risk difference. In similar analyses, both unprocessed red and processed meat
      consumption are associated with incident diabetes, with higher risk per g of
      processed (RR per 50 g: 1.51, 95 %CI = 1.25-1.83) versus unprocessed (RR per 100
      g: 1.19, 95 % CI = 1.04-1.37) meats. Contents of heme iron and dietary
      cholesterol may partly account for these associations. The overall findings
      suggest that neither unprocessed red nor processed meat consumption is beneficial
      for cardiometabolic health, and that clinical and public health guidance should
      especially prioritize reducing processed meat consumption.

PMID- 23001746
TI  - Mechanisms of weight loss, diabetes control and changes in food choices after
      gastrointestinal surgery.
AB  - The long-term effects of lifestyle changes, diet and medical therapy on obesity
      are limited. Bariatric surgery is the most effective long-term treatment with the
      greatest chances for amelioration of obesity-associated complications, including
      type 2 diabetes mellitus (T2DM). There is increasing evidence in the literature
      that bariatric operations have a profound effect on human physiology, by reducing
      hunger, increasing satiety, paradoxically increasing energy expenditure, and even
      promoting healthy food preferences. Some of these operations improve glucose
      homeostasis in patients with T2DM independently of weight loss. Changes in the
      gut hormone levels of glucagon-like peptide 1, peptide YY and ghrelin have been
      proposed as some of the mediators implicated in changing physiology. The aim of
      this review is to critically explore the current knowledge on the putative
      mechanisms of the change in weight and improvement in T2DM glycaemic control
      after the most commonly performed bariatric operations.

PMID- 23001748
TI  - The Japanese version of the modified ACR preliminary diagnostic criteria for
      fibromyalgia and the fibromyalgia symptom scale: reliability and validity.
AB  - PURPOSE: The aim of this study is to investigate the reliability and validity of
      the Japanese version of the modified American College of Rheumatology (ACR)
      Preliminary Diagnostic Criteria for Fibromyalgia (mACR 2010-J) and the
      Fibromyalgia Symptom Scale (mFS-J). METHODS: According to the ACR 1990
      classification criteria, patients with chronic pain were divided into the
      fibromyalgia group and nonfibromyalgia group (rheumatoid arthritis and
      osteoarthritis). Patients in both groups were assessed using mACR 2010-J and mFS
      J. RESULTS: 294 of 462 (64 %) patients in the fibromyalgia group met mACR 2010-J,
      whereas 4 % (9/231) of the nonfibromyalgia group did, with sensitivity of 64 %,
      specificity of 96 %, positive predictive value of 97 %, negative predictive value
      of 56 %, and positive likelihood ratio of 16.3. Mean total scores on mFS-J
      significantly differentiated the fibromyalgia from the nonfibromyalgia group.
      According to the value of the Youden index, the best cutoff score for the mFS-J
      was 9/10. CONCLUSION: Our findings indicate that mACR 2010-J as a positive test
      and mFS-J as a quantification scale might be suitable for assessing fibromyalgia
      among Japanese chronic pain populations.

PMID- 23001747
TI  - Crystal structure of mouse RhoA:GTPgammaS complex in a centered lattice.
AB  - RhoA, a member of the Rho sub-family of small GTPases, plays a significant
      signaling role in cell morphogenesis, migration, neuronal development, cell
      division and adhesion. So far, 4 structures of RhoA:GDP/GTP analogs and 14
      structures of RhoA in complex with other proteins have been reported. All
      RhoA:GDP/GTP analog complexes have been crystallized in primitive lattices and
      RhoA is monomeric. This is the first time a RhoA:GTP analog complex has been
      crystallized as a dimer in a centered lattice. The present structure reveals
      structural differences in the switch-I (residues 28-42) and switch-II (residues
      61-66) regions, which play important roles in interactions with downstream
      targets to transduce signals, when compared to the previously reported
      structures.

PMID- 23001749
TI  - The capillaroscopic findings in idiopathic pernio: is it a microvascular disease?
AB  - OBJECTIVES: Pernio is a disorder that affects the unprotected skin regions of
      individuals who are exposed to nonfreezing, damp cold. We aimed to examine
      nailfold capillaries by video capillaroscopy and evaluate the vascular
      involvement in patients with idiopathic pernio. METHODS: Fifty-three patients
      with idiopathic pernio (male/female ratio 35:18, mean age 25 +/- 9 years) and 38
      age- and sex-matched healthy volunteers (male/female ratio 30:8, mean age 24 +/-
      4 years) were included in the study. Forty-seven of the 53 patients and all the
      healthy volunteers were evaluated by nailfold video capillaroscopy. RESULTS: In
      the patient group, the mean capillary diameter and the mean apical capillary
      diameter were 56 +/- 15 and 24 +/- 7 MUm, respectively. In the control group, the
      mean capillary diameter and the mean apical capillary diameter were 37 +/- 8 and
      15 +/- 4 MUm, respectively (both p < 0.001). Both of these differences were
      independent of the disease activity, smoking, and the number of pernio episodes.
      There were no architectural derangements, avascular areas, or hemorrhages.
      CONCLUSIONS: In the present study, increased nailfold capillary diameter and
      increased apical capillary diameter were found in patients with pernio regardless
      of the disease activity. These findings suggest organic damage of the
      microcirculation.

PMID- 23001750
TI  - Noncovalent immobilization of ionic-tagged box-Cu(OAc)2 complex and its
      application in asymmetric Henry reaction.
AB  - Immobilized Cu(OAc)(2)-bis(oxazolines) via hydrogen bonding by SBA-15 was applied
      to asymmetric Henry reaction, and good enantioselectivities were obtained (up to
      83% ee) between 2-methoxybenzaldehyde and CH(3)NO(2) in isopropyl alcohol
      (iPrOH). The catalyst could be reused seven times without any obvious loss in
      enantioselectivity. For the first time, this facile and clean immobilization
      method is applied to the use of bis(oxazolines) complexes.

PMID- 23001751
TI  - Anatomy of ovary and ovule in dandelions (Taraxacum, Asteraceae).
AB  - The genus Taraxacum Wigg. (Asteraceae) forms a polyploid complex within which
      there are strong links between the ploidy level and the mode of reproduction.
      Diploids are obligate sexual, whereas polyploids are usually apomictic. The paper
      reports on a comparative study of the ovary and especially the ovule anatomy in
      the diploid dandelion T. linearisquameum and the triploid T. gentile.
      Observations with light and electron microscopy revealed no essential differences
      in the anatomy of both the ovary and ovule in the examined species. Dandelion
      ovules are anatropous, unitegmic and tenuinucellate. In both sexual and apomictic
      species, a zonal differentiation of the integument is characteristic of the
      ovule. In the integumentary layers situated next to the endothelium, the cell
      walls are extremely thick and PAS positive. Data obtained from TEM indicate that
      these special walls have an open spongy structure and their cytoplasm shows
      evidence of gradual degeneration. Increased deposition of wall material in the
      integumentary cells surrounding the endothelium takes place especially around the
      chalazal pole of the embryo sac as well as around the central cell. In contrast,
      the integumentary cells surrounding the micropylar region have thin walls and
      exhibit a high metabolic activity. The role of the thick-walled integumentary
      layers in the dandelion ovule is discussed. We also consider whether this may be
      a feature of taxonomic importance.

PMID- 23001752
TI  - Randomized clinical trial on the influence of anaesthesia protocol on intestinal
      motility during laparoscopic surgery requiring small bowel anastomosis.
AB  - BACKGROUND: Hyperperistalsis of the small bowel during laparoscopic surgery may
      cause mucosal prolapse and reduce exposure, making laparoscopic suturing or
      stapling more demanding for the surgeon. Although it is commonly accepted that
      both opioids and volatile anaesthetics induce intestinal paralysis, intestinal
      hyperactivity during anaesthesia is not uncommon. This randomized trial
      investigated the effect of different volatile anaesthetics on intestinal motility
      and the impact on surgeon satisfaction. METHODS: Patients scheduled for
      laparoscopic gastric bypass surgery were randomized to receive sevoflurane or
      desflurane in a balanced anaesthetic regimen. After surgical exposure peristaltic
      waves were counted over 1 min in a segment of the jejunum. Following evaluation
      of intestinal motility, N-butylhyoscine, an antimuscarinic anticholinergic agent
      that relaxes bowel smooth muscle cells, could be administered if the surgeon
      judged the intestinal motility as disturbing. The endpoints were number of
      peristaltic waves and incidence of N-butylhyoscine administration, a surrogate
      for surgeon satisfaction. RESULTS: Twenty-two patients were randomized to each
      group. The groups were similar in age, sex and body mass index. There was a
      statistically significant difference in intestinal motility between the
      desflurane and sevoflurane groups: median (range) 7 (0-12) versus 1 (0-10) waves
      counted over 1 min respectively (P < 0.001). A higher proportion of patients in
      the desflurane group received N-butylhyoscine (10 of 22 versus 1 of 22 in the
      sevoflurane group; P = 0.004). CONCLUSION: Desflurane increased intestinal
      motility and decreased surgeon satisfaction compared with sevoflurane during
      laparoscopic gastric bypass surgery. A sevoflurane-based anaesthetic protocol can
      help to avoid disturbing hyperperistalsis. REGISTRATION NUMBER: B39620097060
      (http://www.clinicaltrials.be).

PMID- 23001753
TI  - Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer
      susceptibility in a Chinese Han population.
AB  - Centrosome aberrations have been suggested to cause chromosomal instability and
      aneuploidy, and eventually promote cancer development. The Centrobin and Nek2
      proteins interact with each other and both are involved in centrosome duplication
      and chromosome segregation. This study aimed to investigate whether genetic
      polymorphisms in these two genes may affect breast cancer susceptibility in
      Chinese Han population using a haplotype-based analysis. Five single nucleotide
      polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215
      cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free
      controls from Chinese Han population. The results showed that CATCG haplotype of
      centrobin was strongly associated with decreased breast cancer risk (adjusted OR
      = 0.14, 95 % CI = 0.09-0.22), which was mainly driven by the C allele of SNP
      rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the
      individual SNPs in Nek2 was associated with breast cancer risk. However,
      haplotype GTAT of Nek2 was associated with increased risk of breast cancer
      (adjusted OR = 1.56, 95 % CI = 1.18-2.06) and its risk was significantly elevated
      among women with both family history of cancer and a longer menarche-first full
      term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97
      14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and
      protective haplotype CATCG of centrobin were linked with decreased breast cancer
      risk, suggesting that the association between genetic variants of Nek2 and
      increased breast cancer risk was modified by genetic variants of centrobin. Our
      results indicate that genetic polymorphisms of centrobin and Nek2 are related to
      breast cancer susceptibility in Chinese Han women.

PMID- 23001754
TI  - Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of
      vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative
      platelet proteomics.
AB  - This phase 1 study evaluated the safety and tolerability of antiangiogenic
      therapy using vandetanib and metronomic cyclophosphamide and methotrexate in
      metastatic breast cancer. Eligible patients had metastatic breast cancer with 0-4
      prior chemotherapy regimens. All received cyclophosphamide 50 mg daily,
      methotrexate 2.5 mg days 1-2 weekly, and vandetanib daily in 3 dose-escalation
      cohorts: 100 mg (C1), 200 mg (C2), and 300 mg (C3). The primary endpoint was
      safety and tolerability; secondary endpoints included response rate and
      evaluation of platelet-associated proteins. Twenty three patients were treated
      and evaluable for toxicity. Common mild toxicities included nausea, vomiting,
      LFTs abnormalities, fatigue, and rash. Three episodes of dose-limiting toxicity
      occurred in C3. In all cohorts, 1/3 of patients required vandetanib dose
      reduction, and 22 % ended therapy for toxicity. Of the 20 response-evaluable
      patients, 10 % demonstrated partial response and 15 % stable disease >=24 weeks.
      Proteomic analyses demonstrated changes in platelet content of angiogenesis
      regulators, including vascular endothelial growth factor and platelet factor 4,
      with exposure to therapy. This regimen was tolerable at a maximum vandetanib dose
      of 200 mg; modest clinical activity was observed in this heavily pretreated
      population. Changes in the platelet proteome may serve as pharmacodynamic markers
      of angiogenesis inhibition. Metronomic chemotherapy is an attractive partner with
      biologics and deserves further study in metastatic breast cancer.

PMID- 23001755
TI  - gamma-Secretase inhibitor I induces apoptosis in chronic lymphocytic leukemia
      cells by proteasome inhibition, endoplasmic reticulum stress increase and notch
      down-regulation.
AB  - gamma-Secretase inhibitors (GSIs) have been proposed for combined therapies of
      malignancies with a dysregulated Notch signaling. GSI I (Z-Leu-Leu-Nle-CHO)
      induces apoptosis of some tumor cells by inhibiting proteasome and Notch
      activity. Alterations in these two cell survival regulators contribute to
      apoptosis resistance of chronic lymphocytic leukemia (CLL) cells. Here, we
      investigated the mechanisms whereby GSI I increases apoptosis of primary CLL
      cells. Time-course studies indicate that initial apoptotic events are inhibition
      of proteasome activity, concomitant with an increased endoplasmic reticulum (ER)
      stress apoptotic signaling, and a consistent Noxa protein up-regulation. These
      events precede, and some of them contribute to, mitochondrial alterations, which
      occur notwithstanding Mcl-1 accumulation induced by GSI I. In CLL cells, GSI I
      inhibits Notch1 and Notch2 activation only in the late apoptotic phases,
      suggesting that this event does not initiate CLL cell apoptosis. However, Notch
      inhibition may contribute to amplify GSI I-induced CLL cell apoptosis, given that
      Notch activation sustains the survival of these cells, as demonstrated by the
      evidence that both Notch1 and Notch2 down-regulation by small-interfering RNA
      accelerates spontaneous CLL cell apoptosis. Overall, our results show that GSI I
      triggers CLL cell apoptosis by inhibiting proteasome activity and enhancing ER
      stress, and amplifies it by blocking Notch activation. These findings suggest the
      potential relevance of simultaneously targeting these three important apoptosis
      regulators as a novel therapeutic strategy for CLL.

PMID- 23001756
TI  - Structural analysis of the pyroglutamate-modified isoform of the Alzheimer's
      disease-related amyloid-beta using NMR spectroscopy.
AB  - The aggregation of the Abeta plays a fundamental role in the pathology of AD.
      Recently, N-terminally modified Abeta species, pE-Abeta, have been described as
      major constituents of Abeta deposits in the brains of AD patients. pE-Abeta has
      an increased aggregation propensity and shows increased toxicity compared with
      Abeta1-40 and Abeta1-42. In the present work, high-resolution NMR spectroscopy
      was performed to study pE-Abeta3-40 in aqueous TFE-containing solution. Two
      dimensional TOCSY and NOESY experiments were performed. On the basis of NOE and
      chemical shift data, pE-Abeta3-40 was shown to contain two helical regions formed
      by residues 14-22 and 30-36. This is similar as previously described for Abeta1
      40. However, the secondary chemical shift data indicate decreased helical
      propensity in pE-Abeta3-40 when compared with Abeta1-40 under exactly the same
      conditions. This is in agreement with the observation that pE-Abeta3-40 shows a
      drastically increased tendency to form beta-sheet-rich structures under more
      physiologic conditions. Structural studies of pE-Abeta are crucial for better
      understanding the structural basis of amyloid fibril formation in the brain
      during development of AD, especially because an increasing number of reports
      indicate a decisive role of pE-Abeta for the pathogenesis of AD.

PMID- 23001757
TI  - A study on the evaluations of emission factors and uncertainty ranges for methane
      and nitrous oxide from combined-cycle power plant in Korea.
AB  - In this research, in order to develop technology/country-specific emission
      factors of methane (CH(4)) and nitrous oxide (N(2)O), a total of 585 samples from
      eight gas-fired turbine combined cycle (GTCC) power plants were measured and
      analyzed. The research found that the emission factor for CH(4) stood at "0.82
      kg/TJ", which was an 18 % lower than the emission factor for liquefied natural
      gas (LNG) GTCC "1 kg/TJ" presented by Intergovernmental Panel on Climate Change
      (IPCC). The result was 8 % up when compared with the emission factor of Japan
      which stands at "0.75 kg/TJ". The emission factor for N(2)O was "0.65 kg/TJ",
      which is significantly lower than "3 kg/TJ" of the emission factor for LNG GTCC
      presented by IPCC, but over six times higher than the default N(2)O emission
      factor of LNG. The evaluation of uncertainty was conducted based on the estimated
      non-CO(2) emission factors, and the ranges of uncertainty for CH(4) and N(2)O
      were between -12.96 and +13.89 %, and -11.43 and +12.86 %, respectively, which is
      significantly lower than uncertainties presented by IPCC. These differences
      proved that non-CO(2) emissions can change depending on combustion technologies;
      therefore, it is vital to establish country/technology-specific emission factors.

PMID- 23001758
TI  - Iophenoxic acid derivatives as markers of oral baits to wildlife. New tools for
      their detection in tissues of a game species and safety considerations for human
      exposure.
AB  - The bait-marker iophenoxic acid (IPA) and its derivatives are increasingly used
      for evaluating and optimizing the cost-effectiveness of baiting campaigns on
      wildlife, particularly on game species such as the wild boar. We aimed to
      determine whether concentrations of the three main IPA derivatives ethyl, methyl
      and propyl-IPA measured on thoracic liquid extracts (TLE) of hunted wild boars
      may be representative of two exposure doses, 40 and 200 mg, from 20 to 217 days
      after ingestion. Then we developed a method of detection of the three IPA
      derivatives by LC/ESI-MS-MS in muscle and liver to evaluate the suitability of
      these two other tissues for monitoring the marked bait consumption and for
      measuring available residues in the meat of marked animals. Three semi-captive
      wild boars received 40 mg of each IPA derivative, three received 200 mg, and
      three, as controls, did not receive IPA. Blood serum was sampled 20, 197 or 217
      days after IPA exposure according to animals and to the derivative. Wild boars
      were shot by gun after the different times of serum sampling times, and TLE,
      muscle and liver were sampled. Our results suggest that TLE is not a relevant
      tissue for quantitatively expressing IPA exposure. Due to interference, no
      analytical method was validated on TLE containing digestive material. On the
      other hand, quantifications in the muscle and particularly in the liver could
      discriminate wild boars that had ingested the two IPA doses from 20 days until 7
      months after exposure, especially for the two long term markers ethyl and propyl
      IPA. So IPA quantifications in the liver sampled on hunted animals appear to be a
      reliable tool for monitoring bait consumption in the field at a large scale.
      Nevertheless, whatever the ingested dose, ethyl- and propyl-IPA concentrations
      measured in the muscle and the liver of tested animals until 217 days after
      exposure, remained higher than 0.01 mg/kg, the Maximal Residue Limit (MRL) is
      recommended for molecules for which no toxicological data are available. Based on
      the range of IPA residues available in these two tissues, implications for humans
      consuming marked animals are discussed.

PMID- 23001759
TI  - Protozoa interaction with aquatic invertebrate: interest for watercourses
      biomonitoring.
AB  - Toxoplasma gondii, Cryptosporidium parvum, and Giardia duodenalis are human
      waterborne protozoa. These worldwide parasites had been detected in various
      watercourses as recreational, surface, drinking, river, and seawater. As of
      today, water protozoa detection was based on large water filtration and on sample
      concentration. Another tool like aquatic invertebrate parasitism could be used
      for sanitary and environmental biomonitoring. In fact, organisms like filter
      feeders could already filtrate and concentrate protozoa directly in their tissues
      in proportion to ambient concentration. So molluscan shellfish can be used as a
      bioindicator of protozoa contamination level in a site since they were sedentary.
      Nevertheless, only a few researches had focused on nonspecific parasitism like
      protozoa infection on aquatic invertebrates. Objectives of this review are
      twofold: Firstly, an overview of protozoa in worldwide water was presented.
      Secondly, current knowledge of protozoa parasitism on aquatic invertebrates was
      detailed and the lack of data of their biological impact was pointed out.

PMID- 23001760
TI  - Development of benzophenone-alkyne bifunctional sigma receptor ligands.
AB  - Sigma (sigma) receptors are unique non-opioid binding sites that are associated
      with a broad range of disease states. Sigma-2 receptors provide a promising
      target for diagnostic imaging and pharmacological interventions to curb tumor
      progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been
      shown to have sigma2 receptor-like binding properties, thus highlighting the need
      to understand the biological function of an 18 kDa protein that exhibits sigma2
      like photoaffinity labeling (denoted here as sigma2-18k) but the amino acid
      sequence of which is not known. In order to provide new tools for the study of
      the sigma2-18k protein, we have developed bifunctional sigma receptor ligands
      each bearing a benzophenone photo-crosslinking moiety and an alkyne group to
      which an azide-containing biotin affinity tag can be covalently attached through
      click chemistry after photo-crosslinking. Although several compounds showed
      favorable sigma2 binding properties, the highest affinity (2 nM) and the greatest
      potency in blocking photolabeling of sigma2-18k by a radioactive photoaffinity
      ligand was shown by compound 22. These benzophenone-alkyne sigma receptor ligands
      might therefore be amenable for studying the sigma2-18k protein through chemical
      biology approaches. To the best of our knowledge, these compounds represent the
      first reported benzophenone-containing clickable sigma receptor ligands, which
      might potentially have broad applications based on the "plugging in" of various
      tags.

PMID- 23001762
TI  - A new mussel-inspired polydopamine sensitizer for dye-sensitized solar cells:
      controlled synthesis and charge transfer.
AB  - The efficient electron injection by direct dye-to-TiO(2) charge transfer and
      strong adhesion of mussel-inspired synthetic polydopamine (PDA) dyes with TiO(2)
      electrode is demonstrated. Spontaneous self-polymerization of dopamine using dip
      coating (DC) and cyclic voltammetry (CV) in basic buffer solution were applied to
      TiO(2) layers under a nitrogen atmosphere, which offers a facile and reliable
      synthetic pathway to make the PDA dyes, PDA-DC and PDA-CV, with conformal surface
      and perform an efficient dye-to-TiO(2) charge transfer. Both synthetic methods
      led to excellent photovoltaic results and the PDA-DC dye exhibited larger current
      density and efficiency values than those in the PDA-CV dye. Under simulated AM
      1.5 G solar light (100 mW cm(-2)), a PDA-DC dye exhibited a short circuit current
      density of 5.50 mW cm(-2), corresponding to an overall power conversion
      efficiency of 1.2 %, which is almost 10 times that of the dopamine dye-sensitized
      solar cell. The PDA dyes showed strong adhesion with the nanocrystalline TiO(2)
      electrodes and the interface engineering of a dye-adsorbed TiO(2) surface through
      the control of the coating methods, reaction times and solution concentration
      maximized the overall conversion efficiency, resulting in a remarkably high
      efficiency.

PMID- 23001761
TI  - Maternal B vitamin status in pregnancy week 18 according to reported use of folic
      acid supplements.
AB  - SCOPE: Epidemiological studies on the association between pregnancy outcomes and
      use of periconceptional folic acid are often based on maternal reported intake.
      Use of folic acid during pregnancy is associated with a higher socioeconomic
      status known to have an impact on diet quality. We have studied plasma B vitamin
      status according to reported use of folic acid supplements during the
      periconceptional period in Norwegian women. METHODS AND RESULTS: Plasma levels of
      folate, cobalamin, pyridoxal 5'-phosphate (vitamin B6), riboflavin, and the
      metabolic markers total homocysteine, methylmalonic acid and 3-hydro-xykynurenine
      were measured in pregnancy week 18 and related to reported intake of folic acid
      from 4 weeks prior to conception throughout week 18 in 2911 women from the
      Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian
      Institute of Public Health. Being a folic acid user during the periconceptional
      period was associated with a better socioeconomic status, and a higher intake of
      several micronutrients, including vitamins, trace-metals, and omega 3 fatty
      acids. Folic acid users had a significantly better plasma B vitamin status.
      CONCLUSION: Epidemiological data based on maternal reported intake of folic acid
      supplements during pregnancy, should take into account the numerous nutritional
      implications, in addition to higher blood folate levels, of being a folic acid
      user.

PMID- 23001763
TI  - New genes expressed in human brains: implications for annotating evolving
      genomes.
AB  - New genes have frequently formed and spread to fixation in a wide variety of
      organisms, constituting abundant sets of lineage-specific genes. It was recently
      reported that an excess of primate-specific and human-specific genes were
      upregulated in the brains of fetuses and infants, and especially in the
      prefrontal cortex, which is involved in cognition. These findings reveal the
      prevalent addition of new genetic components to the transcriptome of the human
      brain. More generally, these findings suggest that genomes are continually
      evolving in both sequence and content, eroding the conservation endowed by common
      ancestry. Despite increasing recognition of the importance of new genes, we
      highlight here that these genes are still seriously under-characterized in
      functional studies and that new gene annotation is inconsistent in current
      practice. We propose an integrative approach to annotate new genes, taking
      advantage of functional and evolutionary genomic methods. We finally discuss how
      the refinement of new gene annotation will be important for the detection of
      evolutionary forces governing new gene origination.

PMID- 23001764
TI  - Fatalism and cardio-metabolic dysfunction in Mexican-American women.
AB  - BACKGROUND: Mexican-American women are disproportionately vulnerable to cardio
      metabolic dysfunction and related health conditions such as cardiovascular
      disease and diabetes. Research shows that low socioeconomic status contributes to
      this populations excess vulnerability to cardio-metabolic dysfunction, but little
      is known about the contribution of cultural factors to these associations.
      PURPOSE: The current study explored the association between fatalism and cardio
      metabolic dysfunction in a randomly selected community cohort of middle-aged
      Mexican-American women and examined whether fatalism could be conceptualized as a
      pathway linking socioeconomic status to cardio-metabolic dysfunction in this
      population. METHOD: Participants included 300 women (ages 40-65), recruited from
      San Diego communities located near the Mexican border, who completed a self
      administered survey battery and underwent a fasting clinical exam between the
      years 2006 and 2009. RESULTS: Linear regression analyses and mediation analyses
      utilizing bootstrapping procedures were performed to test study hypotheses. After
      controlling for age, menopausal status, and acculturation level, fatalism was
      associated with cardio-metabolic dysfunction. Although slightly attenuated, this
      relationship persisted after accounting for socioeconomic status. In addition,
      individuals of low socioeconomic status displayed more fatalistic beliefs and
      higher cardio-metabolic dysfunction after accounting for relevant covariates.
      Finally, the indirect effect of socioeconomic status on cardio-metabolic
      dysfunction via fatalism reached statistical significance. CONCLUSIONS: Fatalism
      may be an important independent risk factor for cardio-metabolic dysfunction in
      Mexican-American women as well as a mechanism linking socioeconomic status to
      cardio-metabolic health.

PMID- 23001765
TI  - Effects of recombinant human granulocyte colony-stimulating factor on central and
      peripheral T lymphocyte reconstitution after sublethal irradiation in mice.
AB  - Granulocyte colony-stimulating factor (G-CSF) is one of the most critical
      cytokines used for the treatment of acute radiation syndrome (ARS). In addition
      to the hematopoietic effects of G-CSF on the differentiation and proliferation of
      myeloid progenitor cells, G-CSF is also known to have immunomodulatory effects.
      The aim of the present study was to investigate whether G-CSF could accelerate
      central and peripheral T lymphocyte recovery after a sublethal dose of
      irradiation. Female BALB/c mice were subjected to 6 Gy of total body irradiation
      and then were treated with either 100 MUg/kg G-CSF or an equal volume of PBS once
      daily for 14 days. Percentages of thymocyte subpopulations including CD4 - CD8 -
      , CD4 + CD8 + , CD4 + CD8- and CD4 - CD8+ T cells, peripheral CD3 + , CD4+ and
      CD8+ cells were analyzed by flow cytometry. Recent thymic emigrants (RTEs) were
      assessed by real-time polymerase chain reaction (PCR) using primers specific to
      the 257-bp T cell receptor rearrangement excision circles (sjTRECs). The
      proliferative capacity of splenic mononuclear cells upon exposure to ConA was
      measured by using the Cell Count Kit-8 (CCK-8). G-CSF treatment promoted
      thymocyte regeneration, accelerated the recovery of CD4 + CD8+ cells and
      increased the frequency of thymocyte sjTRECs. These effects were more prominent
      at early time points (Day 28) after irradiation. G-CSF also increased the rate of
      recovery of peripheral CD3 + , CD4+ and CD8+ cells and shortened the period of
      severe lymphopenia following irradiation. G-CSF also increased the splenic
      mononuclear cell mitotic responsiveness to ConA more than control-treated cells.
      Our results show that G-CSF accelerates T cell recovery through both thymic
      dependent and thymic-independent pathways, which could be used to increase the
      rate of immune reconstitution after sublethal irradiation.

PMID- 23001766
TI  - Sex differences in the timing of identification among children and adults with
      autism spectrum disorders.
AB  - To examine differences by sex in the timing of identification of individuals with
      autism spectrum disorders (ASD), survey data were collected in the Netherlands
      from 2,275 males and females with autistic disorder, Asperger's syndrome and PDD
      NOS. Among participants < 18 years of age, females with Asperger's syndrome were
      identified later than males. Among participants >= 18 years of age, females with
      autistic disorder were identified later than males. In more recent years, girls
      with Asperger's syndrome are diagnosed later than boys, confirming earlier
      findings. In adults, the delayed timing of diagnosis in females with autistic
      disorder may be related to changing practices in diagnosis over time. Strategies
      for changing clinician behaviour to improve recognition of ASD in females are
      needed.

PMID- 23001767
TI  - Television, video game and social media use among children with ASD and typically
      developing siblings.
AB  - This study examined the nature of television, video game, and social media use in
      children (ages 8-18) with autism spectrum disorders (ASD, n = 202) compared to
      typically developing siblings (TD, n = 179), and relative to other activities.
      Parents completed measures assessing children's screen-based and other
      extracurricular activities. Children with ASD spent approximately 62% more time
      watching television and playing video games than in all non-screen activities
      combined. Compared with TD siblings, children with ASD spent more hours per day
      playing video games (2.4 vs. 1.6 for boys, and 1.8 vs. 0.8 for girls), and had
      higher levels of problematic video game use. In contrast, children with ASD spent
      little time using social media or socially interactive video games.

PMID- 23001768
TI  - Variation in socio-economic burden for caring of children with autism spectrum
      disorder in Oman: caregiver perspectives.
AB  - A cross-sectional study was conducted to investigate whether caregiver's
      variations in socioeconomic status (SES) has direct bearing on challenges of
      nurturing children with autism spectrum disorder (ASD) in Oman. A cadre of
      caregivers (n = 150) from two types of SES (low-income and middle-high income)
      were compared based on four domains: (1) accessing and perception of remedial
      services, (2) utilization and perception of psychiatric services, (3) constraints
      for being a caregiver of children with ASD and (4) financial expenses of taking
      care of children with ASD. There is little indication that any particular SES
      fare well on these domains. Factors to mitigate such predicaments are therefore
      imperative in order to improve quality of life for caregivers among children with
      ASD.

PMID- 23001769
TI  - Relationship between temperature, hematoma growth, and functional outcome after
      intracerebral hemorrhage.
AB  - BACKGROUND: Fever and hematoma growth are known to be independent predictors of
      poor outcome after intracerebral hemorrhage (ICH). We sought to assess the
      distribution of temperature at different stages in relation to hematoma growth
      and functional outcome at 90 days in a cohort of ICH patients. METHODS: Data of
      patients registered in the Virtual International Stroke Trials Archive--ICH were
      analyzed. Temperatures at baseline, 24, 48, 72, and 168 h were assessed in
      relation to the hematoma growth and functional outcome at 90 days. We calculated
      the daily linear variation of each subject's temperature by subtracting 37 
      degrees C from the maximal daily recorded temperature (delta-temperature). We
      used logistic regression and mixed-effects models to identify factors associated
      with hematoma growth, poor outcome, and temperature elevation after ICH. RESULTS:
      303 patients were included in the analysis. The average age was 66 +/- 12 years,
      200 (66 %) were males, median admission NIHSS was 13 [Interquartile range (IQR),
      9-18), median GCS was 15 (IQR, 14-15). Hematoma growth occurred in 22 % and poor
      functional outcome at 90-days occurred in 41 % of the patients. Cumulative delta
      temperature at 72 h was associated with hematoma growth; age, ICH score, hematoma
      growth, and cumulative delta-temperature at 168 h were associated with poor
      outcome at 90 days. Factors associated with fever in mixed-models were day after
      onset of ICH, hypertension, base hematoma volume, intraventricular-hemorrhage,
      pneumonia, and hematoma growth. CONCLUSIONS: There is a temporal and independent
      association between fever and hematoma growth. Fever after ICH is associated with
      poor outcome at 90 days. Future research is needed to study the mechanisms of
      this phenomenon and if early protocols of temperature modulation would be
      associated with improved outcomes after ICH.

PMID- 23001770
TI  - The effect of gastrointestinal surgery on insulin resistance and insulin
      secretion.
AB  - Diabesity is a term often used to indicate the association of type-2 diabetes
      mellitus (T2DM) with obesity; the prevalence of both conditions is rapidly
      increasing worldwide and has reached epidemic proportions. Insulin resistance
      represents the major determinant of T2DM, which becomes manifest once relative
      beta-cell failure ensues and insulin secretion is no longer sufficient to
      compensate for insulin resistance. In recent years, gastrointestinal surgery has
      emerged as the most effective option for the treatment of obesity and diabetes,
      with level-1 evidence of diabetes remission. Restrictive gastric operations such
      as gastric banding can improve insulin resistance in proportion to weight loss,
      while gastrointestinal bypass procedures, such as roux-en-y gastric-bypass (RYGB)
      and biliopancreatic diversion (BPD), can improve glucose homeostasis even before
      a significant weight loss is reached, suggesting weight-independent mechanisms of
      action. Studies comparing RYGB to BPD show that RYGB primarily enhances insulin
      secretion and reduces hepatic glucose output, whereas BPD rapidly improves
      glycemia primarily through the normalization of insulin sensitivity. Given the
      fact that BPD involves a significantly longer bypass of the proximal intestine
      than RYGB, these data suggest that the exclusion of a greater length of small
      bowel from the transit of food may cause broader and more profound influence on
      insulin sensitivity.

PMID- 23001772
TI  - [RoFo: prospects and challenges for the future].

PMID- 23001771
TI  - Magnetic resonance elastography of the brain using multishot spiral readouts with
      self-navigated motion correction.
AB  - Magnetic resonance elastography (MRE) has been introduced in clinical practice as
      a possible surrogate for mechanical palpation, but its application to study the
      human brain in vivo has been limited by low spatial resolution and the complexity
      of the inverse problem associated with biomechanical property estimation. Here,
      we report significant improvements in brain MRE data acquisition by reporting
      images with high spatial resolution and signal-to-noise ratio as quantified by
      octahedral shear strain metrics. Specifically, we have developed a sequence for
      brain MRE based on multishot, variable-density spiral imaging, and three
      dimensional displacement acquisition and implemented a correction scheme for any
      resulting phase errors. A Rayleigh damped model of brain tissue mechanics was
      adopted to represent the parenchyma and was integrated via a finite element-based
      iterative inversion algorithm. A multiresolution phantom study demonstrates the
      need for obtaining high-resolution MRE data when estimating focal mechanical
      properties. Measurements on three healthy volunteers demonstrate satisfactory
      resolution of gray and white matter, and mechanical heterogeneities correspond
      well with white matter histoarchitecture. Together, these advances enable MRE
      scans that result in high-fidelity, spatially resolved estimates of in vivo brain
      tissue mechanical properties, improving upon lower resolution MRE brain studies
      that only report volume averaged stiffness values.

PMID- 23001774
TI  - Administration of calcitonin promotes blastocyst implantation in mice by up
      regulating integrin beta3 expression in endometrial epithelial cells.
AB  - STUDY QUESTION: Does exogenous calcitonin improve the efficiency of implantation
      in mice by increasing uterine receptivity? SUMMARY ANSWER: The administration of
      calcitonin could improve the efficiency of implantation by increasing the
      expression of several receptivity-related genes in endometrial epithelial cells
      (EECs). WHAT IS KNOWN ALREADY: Calcitonin is one of the biomarkers of uterine
      receptivity, which is transiently produced in the uterine epithelia during the
      period of implantation both in humans and mouse. STUDY DESIGN, SIZE, DURATION:
      Hormone-replaced mice were used for in vivo experiments. To evaluate the effect
      of calcitonin on uterine receptivity, the expression of endometrial genes was
      analyzed 36 h after i.p. injection of 0.5 IU calcitonin in a treatment group
      versus saline in the control. To evaluate the effect of calcitonin on
      implantation efficiency in vivo, two groups received 0.5 IU or 2 IU calcitonin
      (i.p.) 24 h before embryo transfer, and a control group received saline (i.p.) (n
      = 18 mice per group). Implantation sites were counted 7 days after embryo
      transfer. The RL95-2 human endometrial carcinoma cell line was used to study the
      mechanisms underlying the effect of calcitonin on gene expression in the
      endometria. Using an in vitro model of endometrium-trophoblast interaction,
      established with RL95-2 cells and JAR (human choriocarcinoma cell line)
      trophoblast, endometrial receptivity was evaluated by comparing attachment and
      outgrowth of JAR spheroids in control and treatment groups.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Uterine receptivity in ovariectomized
      mice was induced by injection of estradiol and progesterone. Expression of eight
      genes in murine endometrium and RL95-2 cells was analyzed by real-time RT-PCR,
      western blot, immunohistochemical analysis, flow cytometry and enzyme-linked
      immunosorbent assay. We tested the effects of a protein kinase C inhibitor,
      matrigel and an antibody against integrin alphavbeta3 using RL95-2 cells and
      performed attachment and outgrowth assays using the in vitro model of endometrium
      trophoblast interaction. Implantation efficiency was evaluated by counting the
      implantation sites after embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE:
      Calcitonin up-regulated alphavbeta3 in RL95 cells, which in turn resulted in
      increased levels of the leukemia inhibitory factor (LIF) and heparin binding
      epidermal growth factor (HB-EGF) mRNA (both P < 0.01 versus control) and protein
      (both P < 0.05 versus control). The attachment and expansion of JAR spheroids was
      promoted by pretreatment of EECs with calcitonin (P < 0.05 versus control)
      together with significantly increased expression of alphavbeta3, LIF and HB-EGF.
      Moreover, the injection of calcitonin in the preimplantation phase increased the
      total number of implantation sites in treatment groups (55 in control versus 78
      and 85 in 0.5 and 2 IU groups, respectively). Compared with the control group
      (3.11 +/- 2.14), the average number of implantation sites in the 2 IU calcitonin
      treatment group increased (4.72 +/- 1.87, P = 0.022). LIMITATIONS, REASONS FOR
      CAUTION: Experiments were performed in mice and human cell lines but not in
      primary cultures of human endometrial cells. WIDER IMPLICATIONS OF THE FINDINGS:
      The findings presented here have important implications, in that calcitonin
      administration (currently used for treatment of hypercalcemia or osteoporosis)
      may have clinical benefits in assisted reproduction programs, by facilitating
      endometrial receptivity and embryo implantation. However, further studies are
      required to confirm these findings. STUDY FUNDING/COMPETING INTEREST(S): This
      work was supported by National Science Foundation of China (No. 81170619). There
      are no financial or commercial conflicts in this study.

PMID- 23001775
TI  - How common is adenomyosis? A prospective study of prevalence using transvaginal
      ultrasound in a gynaecology clinic.
AB  - STUDY QUESTION: What is the prevalence of adenomyosis in a population of women
      attending a general gynaecological clinic? SUMMARY ANSWER: Adenomyosis was
      present in 206 of 985 [20.9%; 95% confidence interval (CI): 18.5-23.6%] women
      included in the study. WHAT IS KNOWN ALREADY: Previous studies of occurrence of
      adenomyosis have been limited to women who underwent hysterectomy, which is
      likely to overestimate its prevalence compared with the general population of
      women. There are no large prospective studies on the prevalence of adenomyosis,
      either in the general population of women or in a general gynaecology clinic
      setting. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study
      set in the general gynaecology clinic of a university teaching hospital between
      January 2009 and January 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: There
      were 985 consecutive women who attended the clinic and underwent structured
      clinical and transvaginal ultrasound examination in accordance with the study
      protocol. Morphological features of adenomyosis were systematically recorded with
      the ultrasound scan to determine its prevalence and factors which may affect its
      occurrence. MAIN RESULTS AND THE ROLE OF CHANCE: Adenomyosis was present in
      206/985 [20.9% (95% CI: 18.5-23.6%)] women included in the study. Multivariate
      analysis showed that the prevalence of adenomyosis was significantly associated
      with women's age, gravidity and pelvic endometriosis (P< 0.001). In women who
      subsequently underwent hysterectomy, there was a good level of agreement between
      the ultrasound and histological diagnosis of adenomyosis [kappa = 0.62 (P =
      0.001), 95% CI (0.324, 0.912)]. LIMITATIONS, REASONS FOR CAUTION: Our estimate of
      prevalence of adenomyosis is likely to be higher than in the general population
      as we studied symptomatic women attending a gynaecology clinic. WIDER
      IMPLICATIONS OF THE FINDINGS: Better estimates of the prevalence of adenomyosis
      can improve our understanding of the burden of the disease, help to identify
      women at high risk of developing the condition and facilitate the development of
      preventative strategies and effective treatment. STUDY FUNDING/COMPETING
      INTEREST(S): The authors have no competing interests to declare. The study was
      not supported by an external grant.

PMID- 23001776
TI  - Semen quality is influenced by androgen receptor and aromatase gene synergism.
AB  - STUDY QUESTION: Does synergism between AR(CAG)(n) and CYP19(TTTA)(n)
      polymorphisms influence the quality of sperm? SUMMARY ANSWER: AR(CAG)(n) and
      CYP19(TTTA)(n) polymorphisms had a synergistic effect on sperm concentration and
      motility. WHAT IS KNOWN ALREADY: Androgens exert their action in the testicular
      tissue by binding to androgen receptor (AR), while their action is mediated by
      the aromatase P450 enzyme (CYP19). AR(CAG)(n) alleles are associated with sperm
      motility and CYP19(TTTA)(n) allelic variants have implications for sperm
      concentration and motility. STUDY DESIGN, SIZE, DURATION: Two hundred
      oligozoospermic and 250 normozoospermic men who presented for infertility
      investigation were examined during a period of 2 years. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Conventional semen analysis was performed. DNA was extracted
      from spermatozoa and both polymorphisms were genotyped by polymerase chain
      reaction. Serum hormone levels were determined. MAIN RESULTS AND THE ROLE OF
      CHANCE: Six combined genotypes were identified between the 18 AR(CAG)(n) alleles
      with 12-32 repeats and the 6 CYP19(TTTA)(n) alleles with 7-12 repeats. A gradual
      reduction in the sperm concentration (10(6)/ml) and motility (%) from long AR
      allele-non-CYP19(TTTA)(7) allele carriers to long AR allele-CYP19(TTTA)(7)
      homozygotes and from short AR allele-non-CYP19(TTTA)(7) carriers to short AR
      allele-CYP19(TTTA)(7) homozygotes was observed in normozoospermic men (means +/-
      SD; concentration: 93 +/- 53.1 versus 65 +/- 48.6 and 85 +/- 60.1 versus 37 +/-
      17.2l, P < 0.002; motility: 63 +/- 10.3 versus 55 +/- 14.5 and 52 +/- 19.6 versus
      41 +/- 13.7, P < 0.001, respectively). Similar associations were observed in
      oligozoospermic men (concentration: 10 +/- 4.2 versus 9 +/- 5.9 and 10 +/- 6.3
      versus 6 +/- 3.1, P < 0.03; motility: 47 +/- 17.1 versus 39 +/- 6.2 and 39 +/- 22
      versus 27 +/- 18.3, P < 0.003, respectively). The above associations of the
      combined genotypes with sperm concentration and motility were confirmed in the
      total study population (P < 0.006 and P < 0.001, respectively). LIMITATIONS,
      REASONS FOR CAUTION: Our study population was limited to Greek Caucasian adult
      males, residents of Northwest Greece. WIDER IMPLICATIONS OF THE FINDINGS: The
      confirmation of our findings in other populations would verify the significance
      of AR and CYP19 genes for spermatogenesis. STUDY FUNDING/COMPETING INTERESTS:
      This study did not receive any specific grant from any funding agency in the
      public, commercial or not-for-profit sector. The authors declare no conflicts of
      interest.

PMID- 23001777
TI  - Role of prostaglandin E2 in bacterial growth in women with endometriosis.
AB  - STUDY QUESTION: Can prostaglandin E(2) (PGE(2)) in menstrual and peritoneal fluid
      (PF) promote bacterial growth in women with endometriosis? SUMMARY ANSWER: PGE(2)
      promotes bacterial growth in women with endometriosis. WHAT IS KNOWN ALREADY:
      Menstrual blood of women with endometriosis is highly contaminated with
      Escherichia coli (E. coli) compared with that of non-endometriotic women: E. coli
      derived lipopolysaccharide (LPS) promotes the growth of endometriosis. STUDY
      DESIGN, SIZE AND DURATION: Case-controlled biological research with a prospective
      collection of body fluids and endometrial tissues from women with and without
      endometriosis with retrospective evaluation. PARTICIPANTS/MATERIALS, SETTING AND
      METHODS: PF and sera were collected from 58 women with endometriosis and 28 women
      without endometriosis in an academic research laboratory. Menstrual blood was
      collected from a proportion of these women. Macrophages (Mphi) from PF and
      stromal cells from eutopic endometria were isolated in primary culture. The
      exogenous effect of PGE(2) on the replication of E. coli was examined in a
      bacterial culture system. Levels of PGE(2) in different body fluids and in the
      culture media of Mphi and stromal cells were measured by ELISA. The effect of
      PGE(2) on the growth of peripheral blood lymphocytes (PBLs) was examined. MAIN
      RESULTS AND THE ROLE OF CHANCE: The PGE(2) level was 2-3 times higher in the
      menstrual fluid (MF) than in either sera or in PF. A significantly higher level
      of PGE(2) was found in the MF and PF of women with endometriosis than in control
      women (P < 0.05 for each). Exogenous treatment with PGE(2) dose dependently
      increased E. coli colony formation when compared with non-treated bacteria.
      PGE(2)-enriched MF was able to stimulate the growth of E. coli in a dilution
      dependent manner; this effect was more significantly enhanced in women with
      endometriosis than in control women (P < 0.05). PGE(2) levels in the culture
      media of LPS-treated Mphi/stromal cells were significantly higher in women with
      endometriosis than in non-endometriosis (P < 0.05 for each). Direct application
      of PGE(2) and culture media derived from endometrial Mphi or stromal cells
      significantly suppressed phytohemagglutinin-stimulated growth of PBLs.
      LIMITATIONS AND REASONS FOR CAUTION: Further studies are needed to examine the
      association between PGE(2)-stimulated growth of E. coli and endotoxin level and
      to investigate the possible occurrence of sub-clinical infection within vaginal
      cavity. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may provide some new
      insights to understand the physiopathology or pathogenesis of the mysterious
      disease endometriosis and may hold new therapeutic potential. STUDY
      FUNDING/COMPETING INTEREST(S): This work was supported by grants-in-aid for
      Scientific Research from the Ministry of Education, Sports, Culture, Science and
      Technology of Japan. There is no conflict of interest related to this study.
      TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 23001778
TI  - Long-term follow-up of laparoscopic electrocautery of the ovaries versus
      ovulation induction with recombinant FSH in clomiphene citrate-resistant women
      with polycystic ovary syndrome: an economic evaluation.
AB  - BACKGROUND: Laparoscopic electrocautery of the ovaries and ovulation induction
      with gonadotrophins are both second line treatments for women with clomiphene
      citrate-resistant polycystic ovary syndrome (PCOS). Long-term follow-up after
      electrocautery versus ovulation induction with gonadotrophins has demonstrated at
      least comparable chances for a first live born child with a reduced need for
      ovulation induction or assisted reproduction treatment and increased chances for
      a second live born child. In this study, we report on the long-term economic
      consequences of both treatment modalities. METHODS: Between February 1998 and
      October 2001, we performed a multi-centre randomized controlled trial (RCT)
      comparing a strategy of laparoscopic electrocautery of the ovaries, followed by
      clomiphene citrate and gonadotrophins when anovulation persisted, and a strategy
      of ovulation induction with gonadotrophins in women with clomiphene citrate
      resistant PCOS. Eight to twelve years after randomization we performed a follow
      up study on reproductive outcome in these women and the fertility treatments they
      had needed including data on direct medical costs of pregnancy and delivery.
      Clinical data included number of treatment cycles, live births, miscarriages,
      ectopic pregnancies and multiple pregnancies. We calculated mean costs per woman
      after randomization until the first live birth. Confidence intervals (CIs) were
      estimated by bootstrapping. RESULTS: We obtained data for an economic analysis on
      159 of the 168 randomized women (95%). In total, 71 of 83 women (86%) allocated
      to the electrocautery strategy and 69 of 85 women (81%) allocated to the
      gonadotrophin strategy had at least one live birth. Given the equivalence between
      the two treatment strategies in terms of a first live birth-the primary outcome
      measure-our analysis focused on the cost difference between the two strategies
      within a mean follow-up time of 8-12 years. The mean costs per first live birth
      after randomization were ?11 176 (95% CI: ?9689-?12 549) for the electrocautery
      group and ?14 423 (95% CI: ?12 239-?16 606) for the recombinant FSH group,
      resulting in significantly lower costs (P < 0.05) per first live birth for women
      allocated to the electrocautery group (mean difference ?3247; 95% CI: ?650
      ?5814). CONCLUSION: In women with clomiphene-resistant PCOS, laparoscopic
      electrocautery of the ovaries results in significantly lower costs per live birth
      than ovulation induction with gonadotrophins for an at least equal effectiveness.

PMID- 23001780
TI  - Feasibility of screening patients for emotional risk factors before in vitro
      fertilization in daily clinical practice: a process evaluation.
AB  - STUDY QUESTION: Is patient screening for emotional risk factors before starting
      IVF treatment feasible? SUMMARY ANSWER: Introduction of screening for emotional
      risk factors by a validated instrument (SCREENIVF) in couples treated by IVF or
      ICSI is feasible, indicated by a moderate to high and stable uptake rate, a high
      acceptance of the process of SCREENIVF, and a high acceptability of the presented
      risk profile by the patients. WHAT IS KNOWN ALREADY: SCREENIVF is a validated
      screening tool to identify women at risk for emotional maladjustment preceding
      the start of their IVF/ICSI treatment. STUDY DESIGN, SIZE AND DURATION: This was
      a prospective cohort study, including data of two cohorts of patients (304 and
      342 patients), with a duration of 3 months per cohort. For the first cohort, we
      sent a process evaluation to 210 patients and it was completed by 91 patients.
      PARTICIPANTS/MATERIALS, SETTING AND METHODS: All 304 patients (male and female)
      who started IVF/ICSI between 1 December 2009 and 28 February 2010 in our tertiary
      IVF clinic were eligible. The uptake rate of SCREENIVF was assessed as the
      response rate to the screening questionnaire. One year later, we re-assessed the
      uptake rate in 342 new patients to assess the stability of the uptake rate. A non
      responder assessment in patients who did not complete SCREENIVF was carried out.
      Finally, patients' characteristics and their experiences with SCREENIVF as well
      as their consequent actions were assessed by an additional process evaluation
      questionnaire sent some months later to 210 patients. MAIN RESULTS AND THE ROLE
      OF CHANCE: The uptake rate of SCREENIVF was 78-80%. One-third of the responders
      were found to be at risk for emotional maladjustment, which was comparable with
      previous studies using SCREENIVF. Of 27 non-responders to SCREENIVF, 41%
      explained non-response by 'no actual need for psychological help' and 19% forgot
      to complete the screening. The response rate to the process evaluation was 43% (n
      = 91). Of these, 90% found the screening was useful, and almost all patients were
      positive about the SCREENIVF questionnaire. Furthermore, 93% recognized
      themselves in the risk profile based on SCREENIVF. Of the patients at risk, 21%
      reported planning to seek professional help, but 46% of the at-risk patients
      experienced travelling distance as an obstacle to seek psychological help. We
      concluded that screening patients for emotional risk factors is feasible. In
      future, psychosocial care offered by the Internet may be promising in meeting the
      barrier of travelling distance. LIMITATIONS, REASONS FOR CAUTION: People were
      asked to fill in SCREENIVF for clinical purposes pretreatment. There might be a
      selection bias in the people who did not fill in SCREENIVF, which may be due to
      already existing psychological problems or language problems. The low response
      rate of the process evaluation questionnaire and the mono-centre evaluation may
      be confounders and may have influenced our analysis opportunities. WIDER
      IMPLICATIONS OF THE FINDINGS: The generalizability of this data is unknown with
      respect to other ethnic groups. Furthermore, more research is needed to evaluate
      psychosocial factors in male partners. Future research should also focus on the
      barriers and facilitators for help-seeking behaviour. STUDY FUNDING/COMPETING
      INTEREST(S): There was no funding for this study and no conflict of interest.

PMID- 23001779
TI  - Effect of maternal obesity on estrous cyclicity, embryo development and
      blastocyst gene expression in a mouse model.
AB  - STUDY QUESTION: Does maternal obesity affect estrous cyclicity, embryo
      development and blastocyst gene expression in mice? SUMMARY ANSWER: Maternal
      obesity alters estrous cyclicity and causes the down-regulation of two key
      metabolite receptors (Slc2a1 and Ldlr) in blastocysts recovered from diet-induced
      obese females, but embryo development is not affected. WHAT IS KNOWN ALREADY:
      Maternal obesity reduces fertility because of effects in the periconception
      period, but its negative influence is on estrous cyclicity, oocyte quality or
      embryo development. STUDY DESIGN, SIZE AND DURATION: This was a randomized study
      based on a mouse model for obesity. Twenty-one outbred NIH Swiss mice were used
      and obesity was induced by a diet high in fat administered for 12 weeks prior to
      breeding to control males. MATERIAL, SETTING AND METHODS: Females were fed either
      a control diet (C, n = 9) or a diet high in fat [diet-induced obesity (DiO), n =
      12] for 12 weeks, and were then co-housed with fertile males. Mice that failed to
      breed during 20 consecutive days were considered infertile. Control and diet
      induced obese females that demonstrated vaginal plugs were euthanized 3.5 days
      after mating, blood was sampled for glucose and hormone measurements, corpora
      lutea counted and embryos recovered; the relative mRNA abundance of 11 candidate
      genes was determined in blastocysts by qPCR. MAIN RESULTS AND THE ROLE OF CHANCE:
      Five DiO females failed to breed and displayed anovulatory ovaries (DiOI),
      whereas the other seven DiO females (DiOF) could breed, albeit over an extended
      period compared with controls. DiOF weighed significantly less than DiOI. Both
      groups had elevated serum insulin compared with C, although blood glucose level
      was only significantly higher than that in controls in the infertile DiOI group.
      Adiponectin was lower in the DiOI and leptin higher in both the DiOI and DiOF
      mice than in C. DiOF ovulated the same number of oocytes as C, and embryo
      development to blastocyst was normal. The expression of genes encoding metabolic
      hormone receptors (Insr, Igf1r, Igf2r, Adipor1, Adipor2 and Lepr) and key
      metabolic enzymes (Gapdh, Cpt1a and Sod2) did not differ between DiOF and C
      blastocysts, but that of metabolite receptors (Slc2a1 and Ldr) was down-regulated
      in DiOF. To limit the role of chance, the experiments were conducted in a defined
      laboratory setting with the proper controls, and the animals were randomly
      assigned to each experimental group. Moreover, a P-value of < 0.05 was chosen to
      determine whether the differences observed between the groups were statistically
      significant. LIMITATIONS AND REASONS FOR CAUTION: The results obtained may not
      fully extrapolate to humans. Also, as follicular activity was not monitored while
      breeding, so the extended breeding period for DiOF group might be explained by
      behavioral abnormalities occurring in normal cycling animals. WIDER IMPLICATIONS
      OF THE FINDINGS: DiO alters the estrous cycle in the mouse model and demonstrates
      a role of obesity in infertility. The data also suggest that in an outbred,
      genetically diverse population, such as the human, individual susceptibility to
      obesity and associated infertility induced by diet exists. The apparently normal
      development to blastocyst observed in fertile, obese females suggests that
      preimplantation embryos can resist potentially adverse outcomes caused by an
      oversupply of fatty acids and glucose under in vivo conditions. This metabolic
      plasticity may, in part, be due to an ability to down-regulate metabolite
      transporters, thereby preventing excessive nutrient uptake. STUDY
      FUNDING/COMPETING INTEREST(S): The research was supported by funds from the
      University of Missouri, grants from the National Institutes of Health and by a
      fellowship from the Lalor Foundation. There were no competing interests. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 23001781
TI  - Common variants in the sex hormone-binding globulin gene (SHBG) and polycystic
      ovary syndrome (PCOS) in Mediterranean women.
AB  - STUDY QUESTION: Is there an association between polycystic ovary syndrome (PCOS)
      and the sex hormone-binding globulin (SHBG) rs1799941, rs6257, rs6259 and
      rs727428 variants in a large series of Mediterranean women? SUMMARY ANSWER: The
      rs727428 and rs6259 variants are associated with PCOS in Mediterranean women.
      WHAT IS KNOWN ALREADY: The level of SHBG, the primary plasma transport protein
      for sex steroids, which regulates the bioavailability of these hormones to target
      tissues, is reduced in patients with PCOS. Single-nucleotide polymorphisms in the
      SHBG gene influence circulating SHBG levels in American patients with PCOS and
      may predict the development of type 2 diabetes. STUDY DESIGN, SIZE AND DURATION:
      This was a genetic case-control association study including 1004 premenopausal
      Mediterranean women. PARTICIPANTS/MATERIALS, SETTING AND METHODS: In an Academic
      setting, we genotyped a clinical cohort consisting of 281 patients with PCOS and
      142 women without any evidence of androgen excess, and a population-based cohort
      comprised of 581 unselected female blood donors from Spain and Italy. The latter
      included 31 patients with PCOS and 550 controls, of whom 298 had no evidence of
      any androgen excess disorder and were considered hyper-normal controls. MAIN
      RESULTS AND THE ROLE OF CHANCE: Mutant alleles of the rs727428 variant were more
      frequent in patients with PCOS compared with controls and with hyper-normal
      controls. This association was independent of obesity. Carrying mutant alleles of
      rs727428 was found to be associated with a 1.29 odds ratio (OR) for PCOS, whereas
      carrying mutant alleles of rs6259 associated with a 0.68 OR for PCOS. The
      rs1799941 and rs6257 variants were not associated with PCOS. None of the SHBG
      variants influenced serum SHBG concentrations. LIMITATIONS AND REASONS FOR
      CAUTION: The associations found here were relatively weak and, arising from a
      case-control study, do not necessarily indicate a causative role of the SHBG
      variants in the development of PCOS. Also, we studied different patients and
      controls from different sources, making some of the interpretations difficult.
      Finally, the rs1799941 variant was not in Hardy-Weinberg equilibrium in the small
      group of patients with PCOS recruited from the general population, yet this
      variant was not associated with PCOS. WIDER IMPLICATIONS OF THE FINDINGS: SHBG
      variants that influenced circulating SHBG levels in American patients with PCOS
      are also associated with this syndrome in Mediterranean women, pointing to SHBG
      as a candidate gene for PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was
      supported by grants PI080944 and PI110357 from Instituto de Investigacion Carlos
      III, Spanish Ministry of Economy and Competitiveness. CIBERDEM is also an
      initiative of Instituto de Investigacion Carlos III. The Authors have no
      competing interests to declare.

PMID- 23001782
TI  - Micro- and macroheterogeneity of N-glycosylation yields size and charge isoforms
      of human sex hormone binding globulin circulating in serum.
AB  - Human sex hormone binding globulin (hSHBG) is a serum glycoprotein central to the
      transport and targeted delivery of sex hormones to steroid-sensitive tissues.
      Several molecular mechanisms of action of hSHBG, including the function of its
      attached glycans remain unknown. Here, we perform a detailed site-specific
      characterization of the N- and O-linked glycosylation of serum-derived hSHBG. MS
      driven glycoproteomics and glycomics combined with exoglycosidase treatment were
      used in a bottom-up and top-down manner to determine glycosylation sites, site
      specific occupancies and monosaccharide compositions, detailed glycan structures,
      and the higher level arrangement of glycans on intact hSHBG. It was found that
      serum-derived hSHBG is N-glycosylated at Asn(351)  and Asn(367)  with average
      molar occupancies of 85.1 and 95.3%, respectively. Both sites are occupied by the
      same six sialylated and partly core fucosylated bi- and triantennary N-Glycoforms
      with lactosamine-type antennas of the form (+/-NeuAcalpha6)Galbeta4GlcNAc. N
      Glycoforms of Asn(367)  were slightly more branched and core fucosylated than
      Asn(351)  N-glycoforms due probably to a more surface-exposed glycosylation site.
      The N-terminal Thr(7)  was fully occupied by the two O-linked glycans
      NeuAcalpha3Galbeta3(NeuAcalpha6)GalNAc (where NeuAc is N-acetylneuraminic acid
      and GalNAc is N-acetylgalactosamine) and NeuAcalpha3Galbeta3GalNAc in a 1:6 molar
      ratio. Electrophoretic analysis of intact hSHBG revealed size and charge
      heterogeneity of the isoforms circulating in blood serum. Interestingly, the size
      and charge heterogeneity were shown to originate predominantly from differential
      Asn(351)  glycan occupancies and N-glycan sialylation that may modulate the hSHBG
      activity. To date, this work represents the most detailed structural map of the
      heterogeneous hSHBG glycosylation, which is a prerequisite for investigating the
      functional aspects of the hSHBG glycans.

PMID- 23001783
TI  - Practical and efficient iridium catalysis for benzannulation: an entry to
      isoindolines.
AB  - Iridium(III) catalysis provides a convenient and general method for the synthesis
      of isoindolines via [2+2+2] cycloaddition reactions of diynes and alkynes. The
      reaction proceeds smoothly in environmentally benign and non-distilled isopropyl
      alcohol, providing highly functionalized aromatic compounds in moderate to
      excellent yields.

PMID- 23001784
TI  - Active chiral fluids.
AB  - Active processes in biological systems often exhibit chiral asymmetries. Examples
      are the chirality of cytoskeletal filaments which interact with motor proteins,
      the chirality of the beat of cilia and flagella as well as the helical
      trajectories of many biological microswimmers. Here, we derive constitutive
      material equations for active fluids which account for the effects of active
      chiral processes. We identify active contributions to the antisymmetric part of
      the stress as well as active angular momentum fluxes. We discuss four types of
      elementary chiral motors and their effects on a surrounding fluid. We show that
      large-scale chiral flows can result from the collective behavior of such motors
      even in cases where isolated motors do not create a hydrodynamic far field.

PMID- 23001785
TI  - Instabilities in wormlike micelle systems. From shear-banding to elastic
      turbulence.
AB  - Shear-banding is ubiquitous in complex fluids. It is related to the organization
      of the flow into macroscopic bands bearing different viscosities and local shear
      rates and stacked along the velocity gradient direction. This flow-induced
      transition towards a heterogeneous flow state has been reported in a variety of
      systems, including wormlike micellar solutions, telechelic polymers, emulsions,
      clay suspensions, colloidal gels, star polymers, granular materials, or foams. In
      the past twenty years, shear-banding flows have been probed by various
      techniques, such as rheometry, velocimetry and flow birefringence. In wormlike
      micelle solutions, many of the data collected exhibit unexplained spatio-temporal
      fluctuations. Different candidates have been identified, the main ones being wall
      slip, interfacial instability between bands or bulk instability of one of the
      bands. In this review, we present experimental evidence for a purely elastic
      instability of the high shear rate band as the main origin for fluctuating shear
      banding flows.

PMID- 23001786
TI  - On the occurrence of polygon-shaped patterns in vibrated cylindrical granular
      beds.
AB  - We report experimental observations of polygon-shaped patterns formed in a
      vertically vibrated bed of circular cross-section. A phase map is determined,
      showing that the polygon pattern is established for Gamma = A(2pif)(2)/g is > or
      approximately equal to 10. The sensitivity of the polygon structure to bed
      parameters was tested by studying beds of different particle sizes and fill
      levels. It was hypothesized that the polygon pattern observed in cylindrical beds
      is the corresponding pattern to the formation of arches in square-shaped beds.
      The close relationship between these two patterns was demonstrated by two
      observations: i) the radii of the arches of a corresponding square bed and the
      inner radius of the cylindrical bed were found to be very similar and ii) the
      boundary lengths of the two patterns were in good agreement.

PMID- 23001787
TI  - Linking the DNA strand asymmetry to the spatio-temporal replication program. I.
      About the role of the replication fork polarity in genome evolution.
AB  - Two key cellular processes, namely transcription and replication, require the
      opening of the DNA double helix and act differently on the two DNA strands,
      generating different mutational patterns (mutational asymmetry) that may result,
      after long evolutionary time, in different nucleotide compositions on the two DNA
      strands (compositional asymmetry). We elaborate on the simplest model of neutral
      substitution rates that takes into account the strand asymmetries generated by
      the transcription and replication processes. Using perturbation theory, we then
      solve the time evolution of the DNA composition under strand-asymmetric
      substitution rates. In our minimal model, the compositional and substitutional
      asymmetries are predicted to decompose into a transcription- and a replication
      associated components. The transcription-associated asymmetry increases in
      magnitude with transcription rate and changes sign with gene orientation while
      the replication-associated asymmetry is proportional to the replication fork
      polarity. These results are confirmed experimentally in the human genome, using
      substitution rates obtained by aligning the human and chimpanzee genomes using
      macaca and orangutan as outgroups, and replication fork polarity determined in
      the HeLa cell line as estimated from the derivative of the mean replication
      timing. When further investigating the dynamics of compositional skew evolution,
      we show that it is not at equilibrium yet and that its evolution is an extremely
      slow process with characteristic time scales of several hundred Myrs.

PMID- 23001788
TI  - Water quality modelling of Lis River, Portugal.
AB  - The aim of the study was to predict the impact of flow conditions, discharges and
      tributaries on the water quality of Lis River using QUAL2Kw model. Calibration of
      the model was performed, based on data obtained in field surveys carried out in
      July 2004 and November 2006. Generally the model fitted quite well the
      experimental data. The results indicated a decrease of water quality in the
      downstream area of Lis River, after the confluence of Lena, Milagres and Amor
      tributaries, as a result of discharges of wastewaters containing degradable
      organics, nutrients and pathogenic organisms from cattle-raising wastewaters,
      domestic effluents and agricultural runoff. The water quality criteria were
      exceeded in these areas for dissolved oxygen, biochemical oxygen demand, total
      nitrogen and faecal coliforms. Water quality modelling in different scenarios
      showed that the impact of tributaries on the quality of Lis River water was quite
      negligible and mainly depends on discharges, which are responsible by an increase
      of almost 45, 13 and 44 % of ultimate carbonaceous biochemical oxygen demand
      (CBOD(u)), ammonium nitrogen and faecal coliforms, for winter simulation, and 23,
      33 and 36 % for summer simulation, respectively, when compared to the real case
      scenario.

PMID- 23001789
TI  - Rhizoremediation of oil-contaminated sites: a perspective on the Gulf War
      environmental catastrophe on the State of Kuwait.
AB  - The Gulf War brought about to the State of Kuwait some of the worst environmental
      pollution as a result of oil spill. Since 1995, research programs have been
      initiated to avoid further damage to the Kuwaiti desert and marine environment
      and to restore and rehabilitate the polluted land, water, and air ecosystems.
      During the following 15 years, different bioremediation methods both on
      laboratory and small field scales were tested and evaluated. The findings of
      these studies were implemented to establish a bio-park in which ornamental shrubs
      and trees were grown in bioremediated soil. This review will focus on Kuwait's
      experience in rhizoremediation and its positive impacts on oil-contaminated
      sites.

PMID- 23001790
TI  - Accumulation of heavy metals and antioxidant responses in Vicia faba plants grown
      on monometallic contaminated soil.
AB  - The purpose of this study was to explore the effects of soil contamination by
      selected metals (cadmium, copper, nickel, lead or zinc) on the antioxidant
      response of Vicia faba plants. The levels of the antioxidants: glutathione,
      proline, non-protein thiols, as well as guaiacol peroxidase and catalase
      activities were measured in the upper parts of plants. Additionally, the
      potential bioavailability of metals in the soil and their concentrations in V.
      faba plants were compared. Treatment with metal caused the problem of an
      elevation in its bioavailability in soil and its concentration in leaves and
      stems. The most serious problems seemed to be metal elevations in soil,
      especially Zn and Ni as well as in the aerial parts of V. faba plants. The
      antioxidant responses appeared to be metal specific. The elevation of guaiacol
      peroxidase activity in leaves and stems as well as the proline in leaves was the
      only more general reaction to metal exposure. Upon analysis of the effects of
      soil metal contamination on V. faba plants, we recommend the use of some
      measurements such as guaiacol peroxidase activity and proline level as useful
      tools in biological monitoring.

PMID- 23001791
TI  - Systematic review and meta-analysis of safety of laparoscopic versus open
      appendicectomy for suspected appendicitis in pregnancy.
AB  - BACKGROUND: Laparoscopic appendicectomy has gained wide acceptance as an
      alternative to open appendicectomy during pregnancy. However, data regarding the
      safety and optimal surgical approach to appendicitis in pregnancy are still
      controversial. METHODS: This was a systematic review and meta-analysis of studies
      comparing laparoscopic and open appendicectomy in pregnancy identified using
      PubMed and Scopus search engines from January 1990 to July 2011. Two reviewers
      independently extracted data on fetal loss, preterm delivery, wound infection,
      duration of operation, hospital stay, Apgar score and birth weight between
      laparoscopic and open appendicectomy groups. RESULTS: Eleven studies with a total
      of 3415 women (599 in laparoscopic and 2816 in open group) were included in the
      analysis. Fetal loss was statistically significantly worse in those who underwent
      laparoscopy compared with open appendicectomy; the pooled relative risk (RR) was
      1.91 (95 per cent confidence interval (c.i.) 1.31 to 2.77) without heterogeneity.
      The pooled RR for preterm labour was 1.44 (0.68 to 3.06), but this risk was not
      statistically significant. The mean difference in length of hospital stay was -
      0.49 (-1.76 to - 0.78) days, but this was not clinically significant. No
      significant difference was found for wound infection, birth weight, duration of
      operation or Apgar score. CONCLUSION: The available low-grade evidence suggests
      that laparoscopic appendicectomy in pregnant women might be associated with a
      greater risk of fetal loss.

PMID- 23001793
TI  - Stereoselective interaction between tetrahydropalmatine enantiomers and CYP
      enzymes in human liver microsomes.
AB  - Tetrahydropalmatine (THP), with one chiral center, is an alkaloid that possesses
      analgesic and many other pharmacological actives. The aim of the present study is
      to investigate stereoselective metabolism of THP enantiomers in human liver
      microsomes (HLM) and elucidate which cytochrome P450 (CYP) isoforms contribute to
      the stereoselective metabolism in HLM. Additionally, the inhibitions of THP
      enantiomers on activity of CYP enzymes are also investigated. The results
      demonstrated that (+)-THP was preferentially metabolized by HLM. Ketoconazole
      (inhibitor of CYP3A4/5) inhibited metabolism of (-)-THP or (+)-THP at same
      degree, whereas the inhibition of fluvoxamine (inhibitor of CYP1A2) on metabolism
      of (+)-THP was greater than that of (-)-THP; moreover, the metabolic rate of (+)
      THP was 5.3-fold of (-)-THP in recombinant human CYP1A2. Meanwhile, THP
      enantiomers did not show obvious inhibitory effect on the activity of various CYP
      isoforms (CYP1A2, 2A6, 2C8, 2C9, 2C19, 2E1, and 3A4/5), whereas (-)-THP, but not
      (+)-THP, significantly inhibited the activity of CYP2D6 with the Ki value of 6.42
      +/- 0.38 MUM. The results suggested that THP enantiomers were predominantly
      metabolized by CYP3A4/5 and CYP1A2 in HLM, and (+)-THP was preferentially
      metabolized by CYP1A2, whereas CYP3A4/5 contributed equally to metabolism of (-)
      THP or (+)-THP. Besides, the inhibition of CYP2D6 by (-)-THP may cause drug-drug
      interaction, which should be considered.

PMID- 23001792
TI  - Inhibition of PRC2 histone methyltransferase activity increases TRAIL-mediated
      apoptosis sensitivity in human colon cancer cells.
AB  - Colorectal cancer is ranked among the top leading causes of cancer death in
      industrialized populations. Polycomb group proteins, including Suz12 and Ezh2,
      are epigenetic regulatory proteins that act as transcriptional repressors of many
      differentiation-associated genes and are overexpressed in a large subset of
      colorectal cancers. Retinoic acid (RA) acts as a negative regulator of PcG
      actions in stem cells, but has shown limited therapeutic potential in some solid
      tumors, including colorectal cancer, in part because of retinoic acid receptor
      beta silencing. Through treatment with RA, Suz12 shRNA knockdown, or Ezh2
      pharmacological inhibition with 3-deazaneplanocin A (DZNep), we increased TRAIL
      mediated apoptosis in human colorectal cancer cell lines. This increased
      apoptosis in human colon cancer cells after RA or DZNep treatment was associated
      with a ~2.5-fold increase in TNFRSF10B (DR5) transcript levels and a 42%
      reduction in the H3K27me3 epigenetic mark at the TNFRSF10B promoter after DZNep
      addition. Taken together, our findings indicate that pharmacological inhibition
      of Polycomb repressive complex 2 histone methyltransferase activity may
      constitute a new epigenetic therapeutic strategy to overcome RA non
      responsiveness in a subset of colorectal tumors by increasing TRAIL-mediated
      apoptosis sensitivity.

PMID- 23001795
TI  - Investigation of cognitive abilities related to reading and spelling in Korean:
      readers with high, average, and low skill levels.
AB  - In this study, we investigated the characteristics of cognitive abilities as
      predictors of Korean reading and spelling ability, and the characteristics of the
      cognition of reading difficulty in Korean. In 103 Korean third-grade children, we
      tested ability to read and spell, nonverbal intelligence, vocabulary size,
      phonological cognitive processing, visual cognitive processing, and naming speed.
      Our results indicated that receptive vocabulary, phoneme awareness, and naming
      speed served as factors for predicting reading test score; receptive vocabulary
      served as a factor for predicting spelling test score. We found that low reading
      level groups had significantly slower performance on the naming speed task and
      lower scores on the receptive vocabulary test, as compared with the other groups
      (average and high reading-level groups). The present results have implications
      concerning useful tasks for screening for Korean poor readers.

PMID- 23001794
TI  - A tribute to Annemarie Weber (1923-2012).

PMID- 23001796
TI  - Synthesis of multiple-shell WO3 hollow spheres by a binary carbonaceous template
      route and their applications in visible-light photocatalysis.
AB  - Hollow go lightly: well-defined multiple-shell WO(3) hollow spheres were
      synthesized by a facile binary carbonaceous spheres template route. Compared with
      single-shell WO(3) hollow spheres, the unusual porous multiple-shell structure of
      the WO(3) hollow spheres proves to greatly enhance photocatalytic activity toward
      degradation of organic pollutants under visible-light irradiation.

PMID- 23001797
TI  - Orphan lung diseases.

PMID- 23001798
TI  - Idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a specific form of progressive, chronic
      fibrosing interstitial lung disease occurring primarily in older adults and
      limited to the lungs. The prognosis is dire, with half of all patients
      progressing to death from respiratory failure within 3 to 5 years from initial
      diagnosis. The pathogenesis of IPF is complex and incompletely understood, and
      the natural history of this disease is variable and unpredictable. There is no
      widely accepted treatment for IPF, except for lung transplantation. Nevertheless,
      these are important and exciting times for the diagnosis and management of
      patients with IPF. Novel diagnostic approaches (e.g., biomarker-based), improved
      prognostic models, and clinical trials of novel drug agents may alter disease
      management substantially over the next few years. For now, clinicians should
      practice comprehensive management, including symptom-based management, aggressive
      management of comorbidities, and patient education and support.

PMID- 23001799
TI  - Current status of idiopathic nonspecific interstitial pneumonia.
AB  - Pulmonary pathologists were aware of cases of idiopathic interstitial pneumonia
      (IIP) that morphologically did not fit Liebow's classification scheme. These
      cases were labeled as "cellular interstitial pneumonia" or "chronic interstitial
      pneumonia not otherwise specified." The term nonspecific interstitial pneumonia
      (NSIP) was first used in relation to a pattern of lung interstitial inflammation
      seen in association with human immunodeficiency virus (HIV) infection. In 1994
      NSIP was used to indicate a group of subacute or chronic interstitial pneumonias
      characterized morphologically by interstitial inflammation or fibrosis or both,
      with preservation of the lung architecture and the absence of typical findings
      for any of the other main categories of IIP (mainly usual interstitial pneumonia,
      desquamative interstitial pneumonia, and bronchiolitis obliterans organizing
      pneumonia). Although these patients presented with "nonspecific" lung histology
      (categorized as cellular and fibrotic variants), and with a broad spectrum of
      associated clinical conditions, such as connective tissue diseases (CTDs),
      environmental exposure, and previous acute lung injury, they showed some peculiar
      clinical aspects, including favorable response to corticosteroid treatment and
      overall good prognosis.The clinical and radiographic profiles were better defined
      in the last decade. The NSIP pattern is the histological background of a
      subacute/chronic interstitial pneumonitis that may be observed in many
      conditions, including CTD, drug-induced lung disease, hypersensitivity
      pneumonitis, slowly healing diffuse alveolar damage (DAD), relapsing organizing
      pneumonia, occupational exposure, immunodeficiency (mainly HIV infection), graft
      versus host disease (GVHD), familial pulmonary fibrosis, immunoglobulin G4 (IgG4)
      related sclerosing disease, with or without overlap features with Rosai-Dorfman
      disease, multicentric Castleman disease, and myelodysplastic syndrome. Rarely,
      NSIP is the histology recognized in patients with idiopathic interstitial
      pneumonitis, in whom efforts to find potential causative exposures are futile.
      This entity occurs mostly in middle-aged, never-smoker women, with a likely
      association with an autoimmune background. High-resolution computed tomographic
      (HRCT) scans typically demonstrate ground-glass attenuation with a bibasilar
      distribution, or in the fibrotic variant, ground-glass attenuation along with
      reticular lines and traction bronchiectasis. The prognosis is good compared with
      idiopathic pulmonary fibrosis (IPF), and therapeutic options include mainly
      corticosteroids and immunosuppressive agents. Recently a more precise definition
      of clinical profiles and radiographic findings of idiopathic NSIP allows
      consideration of less invasive diagnostic procedures (bronchoalveolar lavage,
      transbronchial lung biopsy). Better understanding of pathogenetic mechanisms
      might widen the therapeutic horizon giving a role to new therapeutic options in
      more severe cases.

PMID- 23001800
TI  - Lymphocytic interstitial pneumonia and other benign lymphoid disorders.
AB  - Nonneoplastic pulmonary lymphoid disorders consist of a complex spectrum of
      diseases for pathologists and pulmonologists alike. Advances in our understanding
      of these disorders in recent years have led to revisions in the classification
      scheme. This review summarizes the clinicoradiological and pathological features
      of several benign pulmonary lymphoid disorders as well as the current knowledge
      regarding their pathogenesis. The disorders discussed include lymphocytic
      interstitial pneumonitis, follicular bronchiolitis, nodular lymphoid hyperplasia,
      inflammatory pseudotumor, Castleman disease, immunoglobulin G4-related disease in
      the lung, and posttransplant lymphoproliferative disease.

PMID- 23001801
TI  - Cryptogenic organizing pneumonia.
AB  - Organizing pneumonia (OP) is a pathological pattern defined by the characteristic
      presence of buds of granulation tissue within the lumen of distal pulmonary
      airspaces consisting of fibroblasts and myofibroblasts intermixed with loose
      connective matrix. This pattern is the hallmark of a clinical pathological
      entity, namely cryptogenic organizing pneumonia (COP) when no cause or etiologic
      context is found. The process of intraalveolar organization results from a
      sequence of alveolar injury, alveolar deposition of fibrin, and colonization of
      fibrin with proliferating fibroblasts. A tremendous challenge for research is
      represented by the analysis of features that differentiate the reversible process
      of OP from that of fibroblastic foci driving irreversible fibrosis in usual
      interstitial pneumonia because they may determine the different outcomes of COP
      and idiopathic pulmonary fibrosis (IPF), respectively. Three main imaging
      patterns of COP have been described: (1) multiple patchy alveolar opacities
      (typical pattern), (2) solitary focal nodule or mass (focal pattern), and (3)
      diffuse infiltrative opacities, although several other uncommon patterns have
      been reported, especially the reversed halo sign (atoll sign). Definitive
      diagnosis is based on (1) a suggestive clinical radiological presentation, (2)
      the demonstration of the characteristic pathological pattern at lung
      histopathology, and (3) exclusion of possible causes. Transbronchial biopsies or
      a transthoracic biopsy may also contribute to the pathological diagnosis. Rapid
      clinical and imaging improvement is obtained with corticosteroid therapy. Because
      of the risk of misdiagnosing alternative conditions that may mimic OP, only
      typical cases may be managed without histopathological confirmation, and patients
      should be followed with particular attention paid to any clue of alternate
      diagnosis, especially in case of incomplete response to treatment. Patients and
      clinicians must be aware of frequent relapses after stopping corticosteroid
      treatment.

PMID- 23001802
TI  - Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse
      alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).
AB  - Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute
      lung injury characterized clinically by acute respiratory failure with bilateral
      lung infiltrates and histologically by diffuse alveolar damage (DAD), a
      combination of findings previously known as the Hamman-Rich syndrome. This review
      aims to clarify the diagnostic criteria of AIP, its relationship with DAD and
      acute respiratory distress syndrome (ARDS), key etiologies that need to be
      excluded before making the diagnosis, and the salient clinical features. Cases
      that meet clinical and pathologic criteria for AIP overlap substantially with
      those that fulfill clinical criteria for ARDS. The main differences between AIP
      and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of
      known etiologies. AIP should also be distinguished from "acute exacerbation of
      IPF," a condition in which acute lung injury (usually DAD) supervenes on
      underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis
      (IPF).

PMID- 23001803
TI  - Lymphangioleiomyomatosis: new concepts in pathogenesis, diagnosis, and treatment.
AB  - Lymphangioleiomyomatosis (LAM) is a slowly progressive lung disease that is
      associated with mutations in tuberous sclerosis complex genes, infiltration of
      the pulmonary parenchyma and lymphatics with neoplastic smooth muscle cells,
      extensive tissue remodeling and architectural distortion of the lung, and tumors
      of the chest and abdomen, including lymphangiomyomas and angiomyolipomas. LAM
      occurs in women in the general population and in patients of both genders with
      tuberous sclerosis. Overt clinical manifestations of LAM occur almost exclusively
      in females, however, and include progressive dyspnea on exertion, recurrent
      pneumothorax, and chylous effusions. The molecular basis of LAM has been
      extensively characterized over the past decade, resulting in the development of a
      targeted therapy. This article reviews emerging approaches to the diagnosis and
      treatment of LAM.

PMID- 23001804
TI  - Pulmonary alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the
      accumulation of surfactant lipids and protein in the alveolar spaces, with
      resultant impairment in gas exchange. The clinical course can be variable,
      ranging from spontaneous resolution to respiratory failure and death. PAP in all
      forms is caused by excessive accumulation of surfactant within the alveolar
      spaces. Autoimmune PAP accounts for the vast majority of cases in humans and is
      caused by autoantibodies to granulocyte-macrophage colony-stimulating factor (GM
      CSF), which results in impaired catabolism and clearance of surfactant lipids and
      proteins. Inherited or congenital forms of PAP are exceptionally rare and caused
      by mutations of genes encoding for surfactant proteins. Secondary forms of PAP
      are associated with diverse clinical disorders and are caused by reduced alveolar
      macrophage numbers or function with resultant reduced pulmonary clearance of
      surfactant. PAP is characterized by progressive exertional dyspnea and
      nonproductive cough with hypoxemia. Bilateral infiltrates are typically present
      on chest radiograph, and high-resolution computed tomography reveals diffuse
      ground-glass opacities and airspace consolidation with interlobular septal
      thickening in a characteristic "crazy paving" pattern. Although surgical lung
      biopsy will provide a definitive diagnosis, a combination of typical clinical and
      imaging features with periodic acid-Schiff (PAS)-positive material on
      bronchoalveolar lavage and transbronchial biopsies is usually sufficient. The
      standard of care for treatment of PAP remains whole lung lavage, but treatment is
      not required in all patients. Autoimmune PAP has also been successfully treated
      with GM-CSF, both inhaled and systemic, but the optimal dose, duration, and route
      of administration of GM-CSF have not been elucidated.

PMID- 23001805
TI  - Obliterative (constrictive) bronchiolitis.
AB  - Obliterative bronchiolitis (OB) (formerly termed bronchiolitis obliterans), is a
      rare fibrotic disorder involving terminal and respiratory bronchioles. The term
      constrictive bronchiolitis is synonymous with OB. Clinically, OB is characterized
      by progressive (often fatal) airflow obstruction, the absence of parenchymal
      infiltrates on chest radiographs, a mosaic pattern of perfusion on high
      resolution computed tomographic scan, poor responsiveness to therapy, and high
      mortality rates. Most cases of OB occur in the context of a specific risk factor.
      Currently, most cases of OB occur in lung transplant recipients with chronic
      allograft rejection or hematopoietic stem cell transplant (HSCT) recipients with
      graft versus host disease (GVHD). Other causes of OB include connective tissue
      disease (CTD) (particularly rheumatoid arthritis); lower respiratory tract
      infections; inhalation injury; exposure or inhalation of toxic fumes, metals,
      dusts, particulate matter, or pollutants; occupational exposures; drug reactions;
      consumption of uncooked leaves of Sauropus androgynus; chronic hypersensitivity
      pneumonia; diffuse neuroendocrine cell hyperplasia; miscellaneous. When no cause
      is identified, the term cryptogenic obliterative bronchiolitis is used. This
      review discusses the salient clinical, radiographic, and histological features of
      OB and presents a management approach.

PMID- 23001806
TI  - Diffuse lung diseases in cigarette smokers.
AB  - Cigarette smoking is a recognized causative agent or precipitant of specific
      diffuse lung diseases characterized by bronchiolar and interstitial lung
      inflammation. Respiratory bronchiolitis-associated interstitial lung disease and
      pulmonary Langerhans cell histiocytosis are now considered smoking-induced
      diffuse lung diseases. Desquamative interstitial pneumonia is also recognized as
      a smoking-induced interstitial pneumonia in most cases. These disorders affect
      relatively young adult smokers and may be progressive. Although distinguishable
      by histopathological and radiographic features, significant overlap occurs in
      many cases with chest radiography and lung histology showing overlapping features
      of smoking-related bronchiolar and interstitial lung injury. Cigarette smoking is
      also recognized as an important precipitant of many acute eosinophilic pneumonia
      cases. Smokers are at higher risk of developing fibrotic interstitial lung
      diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis
      associated interstitial lung disease. Certain smokers also develop combined
      emphysema and lung fibrosis. The avoidance of primary and second-hand cigarette
      smoke is a critical component of management for patients afflicted with these
      smoking-induced diffuse lung diseases. The role of corticosteroids and other
      immunosuppressive treatments in the management of smoking-related interstitial
      lung diseases remains poorly defined and should be reserved for individuals with
      progressive disease despite smoking cessation. Understanding mechanisms by which
      tobacco induces diffuse lung pathology is critical in the pursuit of novel
      therapeutic approaches for these diseases.

PMID- 23001807
TI  - Immunopathology, diagnosis, and management of hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease
      caused by a wide variety of organic particles and certain small-molecular weight
      chemical compounds that provoke an exaggerated immune response in susceptible
      individuals. The clinical manifestations are heterogeneous and have been
      classically described as acute, subacute and chronic. The chronic form has an
      insidious onset over a period of months or years, with progressive dyspnea and
      often evolves to fibrosis. The pathology is characterized by a bronchiolocentric
      interstitial mononuclear cell infiltration, nonnecrotizing poorly formed
      granulomas, cellular pneumonitis and variable degrees of fibrosis. However,
      morphological diagnosis of HP is complicated because the subacute/chronic forms
      may be difficult to distinguish from idiopathic pulmonary fibrosis/usual
      interstitial pneumonia and nonspecific interstitial pneumonia. In general,
      diagnosis of HP represents a challenge for clinicians that need to weigh a
      constellation of clinical, laboratory, radiographic and (when available)
      pathological evidence for each patient to assess the certainty of the diagnosis.
      The cornerstone of therapy is antigen avoidance. Although clinical trials are
      scanty, corticosteroids are usually indicated based upon expert opinion. In this
      review we summarize the current evidence regarding the diagnostic criteria and
      therapeutic strategies as well as the immunopathological mechanisms putatively
      implicated in the development of the disease.

PMID- 23001808
TI  - Update on eosinophilic lung diseases.
AB  - The eosinophilic lung diseases are a group of pulmonary disorders characterized
      by an increase in blood and/or lung eosinophils. These disorders can be primary
      pulmonary disorders or the secondary manifestation of other systemic or pulmonary
      conditions, infection, drug reaction, or malignancy. The approach to a patient
      with eosinophilic lung disease involves a thorough history and physical
      examination, review of exposures and appropriate testing, often including
      bronchoscopy or lung biopsy, to establish a specific etiology and determine
      therapy. Eosinophilic lung disease can be suspected based on either the finding
      of pulmonary disease with blood eosinophilia, pulmonary disease with
      bronchoalveolar lavage eosinophilia, or pulmonary disease with lung tissue
      eosinophilia on lung biopsy.

PMID- 23001809
TI  - Neurofibromatosis-associated diffuse lung disease: case report.
AB  - Since the initial report in 1963 several small case series described an
      association between neurofibromatosis (NF) and interstitial lung disease. To
      date, more than 60 cases of interstitial lung disease associated with NF have
      been reported, but relatively few reports included high-resolution computed
      tomographic (HRCT) scans. Typical findings on HRCT include upper lobe predominant
      cystic and bullous disease, ground-glass opacification, and basilar reticular
      abnormalities. We present the case of a 34-year-old male smoker with NF and HRCT
      findings of diffuse lung disease including bullous emphysema, thin-walled cysts,
      and diffuse ground glass. Although NF-associated diffuse lung disease (NF-DLD) is
      disputed as a clinical entity by some, the case presented here adds to the
      accumulating evidence that NF-DLD is a distinct manifestation of
      neurofibromatosis.

PMID- 23001810
TI  - Differential gene expression and methylation in the retinoid/PPARA pathway and of
      tumor suppressors may modify intestinal tumorigenesis induced by low folate in
      mice.
AB  - SCOPE: Inadequate folate intake increases risk for colorectal cancer. We
      previously showed that low-folate diets induced intestinal tumors in BALB/c mice,
      but not in C57BL/6 mice. We suggested that DNA damage, altered methylation, and
      reduced apoptosis could contribute to tumorigenesis in this model. METHODS AND
      RESULTS: To identify genes involved in tumorigenesis, we compared gene expression
      profiles in preneoplastic intestine of BALB/c and C57BL/6 mice-fed low folate. We
      identified 74 upregulated and 90 downregulated genes in BALB/c compared to
      C57BL/6 mice. We validated decreased expression of Bcmo1 and increased expression
      of Aldh1a, which would be expected to upregulate the peroxisome proliferator
      activated receptor alpha (PPARA) pathway, and confirmed the expected upregulation
      of several Ppara downstream genes. We verified, in BALB/c mice, reduced
      expression of Sprr2a, a gene that increases resistance to oxidative damage, and
      of two oncosuppressors (Bmp5 and Arntl). Low folate increased Ppara and Aldh1a1
      expression, and decreased Bcmo1, Sprr2a, and Bmp5 expression in BALB/c, compared
      to BALB/c on control diets. Bcmo1, Ppara, and Bmp5 showed differential DNA
      methylation related to strain, diet, and/or Mthfr genotype. CONCLUSION: Disturbed
      regulation of the retinoid/PPARA pathway, which influences oxidative damage, and
      altered expression of tumor suppressors may contribute to intestinal
      tumorigenesis induced by low-folate intake.

PMID- 23001811
TI  - Successful tracheal intubation with the McGrath((r)) MAC video laryngoscope after
      failure with the Pentax-AWSTM in a patient with cervical spine immobilization.

PMID- 23001812
TI  - A photosensitive liquid crystal studied by 14N NMR, 2H NMR, and DFT calculations.
AB  - An azobenzene derivative, namely diheptylazobenzene, showing the nematic and
      smectic A liquid crystalline phases, was investigated by means of a combined
      approach based on NMR and DFT calculations. (14)N NMR quadrupole- and chemical
      shift-perturbed spectra were acquired in the whole mesophasic range, providing
      both experimental quadrupolar splittings and chemical shift anisotropy values. On
      the same mesogen, deuterium labelled at the alpha-position of the hydrocarbon
      chain, (2)H NMR quadrupole-perturbed spectra were recorded. The analysis of these
      NMR data was performed with the help of ab initio calculations, in vacuo and by
      taking into account the effect of the anisotropic environment typical of liquid
      crystals, by using the IEF-PCM model. The geometry optimizations of the
      azomesogen in the trans and cis configurations were performed by DFT calculations
      employing the combination of B3LYP functional with the 6-311G(d) basis set. The
      analysis of experimental NMR data was performed by considering the trans
      configuration as the most populated one and the corresponding quadrupolar tensors
      and chemical shielding tensors were determined at the DFT level of theory. The
      main result of this work is the determination of a relatively high and
      temperature-dependent molecular biaxiality of the trans state of this azomesogen.

PMID- 23001813
TI  - Effects of erythropoietin on blood-brain barrier tight junctions in ischemia
      reperfusion rats.
AB  - Administration of recombinant human erythropoietin (rhEPO) protects neurons from
      injury after brain ischemia-reperfusion (I/R), which is in part mediated by
      ameliorating the blood-brain barrier (BBB) leakage. But the mechanism of rhEPO's
      protective effects on BBB remains unclear. This study aims to investigate the
      effects of rhEPO on BBB integrity and the expressions of tight junctions (TJs)
      associated proteins of zonula occluden-1 (ZO-1), occludin, and claudin-5 in
      cerebral I/R rats. These rats underwent 2 h of ischemia and then were reperfused
      for up to 3 and 72 h. Animals were randomly divided into five groups: sham
      operated group, I/R 3 h and I/R 72 h group (2 ml saline was injected
      intraperitoneally just before the onset of ischemia), rhEPO +I/R 3 h, and rhEPO
      +I/R 72 h group (5,000 U/kg rhEPO diluted in 2 ml saline solution was injected
      intraperitoneally just before the onset of ischemia). We verified that rhEPO
      could decrease the BBB leakage induced by I/R injury detected by Evans blue
      extravasation. 2, 3, 5-Triphenyltetrazolium chloride staining results showed that
      rhEPO decreased infarct volume after cerebral I/R. TJ integrity was partly
      restored by rhEPO observed by transmission electron microscopy. The mRNA and
      protein expression levels of ZO-1, occludin, and claudin-5 were significantly
      increased compared with I/R groups at the same reperfusion time point by reverse
      transcriptase-polymerase chain reaction and Western blot assays. The treatment of
      rhEPO induced the redistribution of ZO-1, occludin, and claudin-5 in cerebral
      microvessels observed by immunohistochemical staining. Compared with I/R groups,
      the mRNA level of tumor necrosis factor-alpha (TNF-alpha) in cerebral
      microvessels decreased markedly after rhEPO treatment, accompanied with reduced
      TNF-alpha protein level and nuclear factor-kB (NF-kB) p65 activation detected by
      enzyme-linked immunosorbent assay. These results suggested that the protective
      mechanism of rhEPO on BBB after cerebral I/R injury was associated with the
      upregulation of TJ-associated proteins. The downregulated TNF-alpha levels and NF
      kB activation induced by rhEPO might be involved in this process.

PMID- 23001814
TI  - Proteomic analysis of the mice hippocampus after preconditioning induced by N
      methyl-D-aspartate (NMDA).
AB  - Preconditioning induced by N-methyl-D-aspartate (NMDA) has been used as a
      therapeutic tool against later neuronal insults. NMDA preconditioning affords
      neuroprotection against convulsions and cellular damage induced by the NMDA
      receptor agonist, quinolinic acid (QA) with time-window dependence. This study
      aimed to evaluate the molecular alterations promoted by NMDA and to compare these
      alterations in different periods of time that are related to the presence or lack
      of neuroprotection. Putative mechanisms related to NMDA preconditioning were
      evaluated via a proteomic analysis by using a time-window study. After a
      subconvulsant and protective dose of NMDA administration mice, hippocampi were
      removed (1, 24 or 72 h) and total protein analyzed by 2DE gels and identified by
      MALDI-TOF. Differential protein expression among the time induction of NMDA
      preconditioning was observed. In the hippocampus of protected mice (24 h), four
      proteins: HSP70(B), aspartyl-tRNA synthetase, phosphatidylethanolamine binding
      protein and creatine kinase were found to be up-regulated. Two other proteins,
      HSP70(A) and V-type proton ATPase were found down-regulated. Proteomic analysis
      showed that the neuroprotection induced by NMDA preconditioning altered signaling
      pathways, cell energy maintenance and protein synthesis and processing. These
      events may occur in a sense to attenuate the excitotoxicity process during the
      activation of neuroprotection promoted by NMDA preconditioning.

PMID- 23001815
TI  - Advanced neuroimaging to guide acute stroke therapy.
AB  - Traditionally non-contrast CT has been considered the first choice imaging
      modality for acute stroke. Acute ischemic stroke patients presenting to the
      hospital within 3-hours from symptom onset and without any visible hemorrhages or
      large lesions on CT images are considered optimum reperfusion therapy candidates.
      However, non-contrast CT alone has been unable to identify best reperfusion
      therapy candidates outside this window. New advanced imaging techniques are now
      being used successfully for this purpose. Non-invasive CT or MR angiography
      images can be obtained during initial imaging evaluation for identification and
      characterization of vascular lesions, including occlusions, aneurysms, and
      malformations. Either CT-based perfusion imaging or MRI-based diffusion and
      perfusion imaging performed immediately upon arrival of a patient to the hospital
      helps estimate the extent of fixed core and penumbra in ischemic lesions.
      Patients having occlusive lesions with small fixed cores and large penumbra are
      preferred reperfusion therapy candidates.

PMID- 23001816
TI  - Independent component analysis tractography combined with a ball-stick model to
      isolate intravoxel crossing fibers of the corticospinal tracts in clinical
      diffusion MRI.
AB  - The independent component analysis (ICA) tractography method has improved the
      ability to isolate intravoxel crossing fibers; however, the accuracy of ICA is
      limited in cases with voxels in local clusters lacking sufficient numbers of
      fibers with the same orientations. To overcome this limitation, the ICA was
      combined with a ball-stick model (BSM) ["ICA+BSM"]. An ICA approach is applied to
      identify crossing fiber components in voxels of small cluster, which are
      maximally independent in orientation. The eigenvectors of these components are
      numerically optimized via the subsequent BSM procedure. Simulation studies for
      two or three crossing fibers demonstrate that ICA+BSM overcomes the limitation of
      the original ICA method by refining regional ICA solutions in diffusion
      measurement of a single voxel. It shows 2 degrees -5 degrees  of angular errors
      to isolate two or three fibers, providing a better recovery of simulated fibers
      compared with ICA alone. Human studies show that ICA+BSM achieves high anatomical
      correspondence of corticospinal tracts compared with postmortem corticospinal
      histology, yielding 92.2% true positive detection including both lateral and
      medial projections, compared with 84.1% for ICA alone. This study demonstrates
      that the intravoxel crossing fiber problem in clinical diffusion MRI may be
      sorted out more efficiently by combining ICA with BSM.

PMID- 23001817
TI  - Selective synthesis of 1-O-alkyl(poly)glycerol ethers by catalytic reductive
      alkylation of carboxylic acids with a recyclable catalytic system.
AB  - (Poly)glycerol monoethers were synthesized in good yield and selectivity by the
      catalytic reductive alkylation of glycerol, diglycerol, and triglycerol with
      readily available, cheap and/or bio-sourced carboxylic acids. The reaction was
      catalyzed by 1 mol % of Pd/C under 50 bar H(2) using an acid ion-exchange resin
      as a recyclable cocatalyst. The catalytic system was recycled several times, and
      a mechanism is proposed for this transformation.

PMID- 23001819
TI  - Respiratory illness hospitalizations among pregnant women during influenza
      season, 1998-2008.
AB  - To examine health care burden, pregnancy outcomes and impact of high risk medical
      conditions among pregnancy hospitalizations during influenza season. Length of
      stay, hospitalization charges, and delivery complications were compared between
      hospitalizations with and without respiratory illness and compared by presence of
      high risk medical conditions. Length of stay and hospital charges were
      significantly increased among respiratory illness hospitalizations versus non
      respiratory hospitalizations. Among respiratory illness hospitalization, the odds
      of intrauterine fetal demise were increased (adjusted odds ratio (aOR) 2.50, 95 %
      confidence interval (CI) 1.97-3.18). Among live births, there were higher odds of
      preterm delivery (aOR 3.82, 95 % CI 3.53-4.14), cesarean delivery (aOR 3.47, 95 %
      CI 3.22-3.74), and fetal distress (aOR 2.33, 95 % CI 2.15-2.52). The presence of
      high risk medical conditions did not impact pregnancy outcomes. Among pregnant
      women hospitalized during influenza season, those with respiratory illness were
      more likely than those without respiratory illness to have poor perinatal
      outcomes, regardless of the presence of high risk conditions. Efforts to minimize
      influenza morbidity, including universal vaccination and early antiviral therapy
      should be promoted among all pregnant women. 

PMID- 23001818
TI  - Activation of p38 MAP kinase and stress signalling in fibroblasts from the
      progeroid Rothmund-Thomson syndrome.
AB  - Rothmund-Thomson fibroblasts had replicative lifespans and growth rates within
      the range for normal fibroblasts; however, they show elevated levels of the
      stress-associated p38 MAP kinase, suggestive of stress during growth. Treatment
      with the p38 MAP kinase inhibitor SB203580 increased both lifespan and growth
      rate, as did reduction of oxidative stress using low oxygen in some strains. At
      replicative senescence p53, p21(WAF1) and p16(INK4A) levels were elevated, and
      abrogation of p53 using shRNA knockdown allowed the cells to bypass senescence.
      Ectopic expression of human telomerase allowed Rothmund-Thomson fibroblasts to
      bypass senescence. However, activated p38 was still present, and continuous
      growth for some telomerised clones required either a reduction in oxidative
      stress or SB203580 treatment. Overall, the evidence suggests that replicative
      senescence in Rothmund-Thomson cells resembles normal senescence in that it is
      telomere driven and p53 dependent. However, the lack of RECQL4 leads to enhanced
      levels of stress during cell growth that may lead to moderate levels of stress
      induced premature senescence. As replicative senescence is believed to underlie
      human ageing, a moderate level of stress-induced premature senescence and p38
      activity may play a role in the relatively mild ageing phenotype seen in Rothmund
      Thomson. 

PMID- 23001820
TI  - Preoperative cardiopulmonary exercise testing and risk of early mortality
      following abdominal aortic aneurysm repair.
AB  - BACKGROUND: Cardiopulmonary exercise testing (CPET) provides an objective
      assessment of functional capacity. The aim of this study was to assess whether
      preoperative CPET identifies patients at risk of early death following elective
      open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS:
      Prospective data were collected from a pilot study between September 2005 and
      February 2007, and from all patients who underwent CPET before elective AAA
      repair at two vascular centres between February 2007 and November 2011. Symptom
      limited, maximal CPET was performed on each patient. Univariable and
      multivariable analyses were used to identify risk factors for 30- and 90-day
      mortality. RESULTS: Some 415 patients underwent CPET before elective AAA repair.
      Anaerobic threshold (AT), peak oxygen consumption (peak V.O(2) ) and ventilatory
      equivalents for carbon dioxide were associated with 30- and 90-day mortality on
      univariable analysis. On multivariable analysis, open repair (odds ratio (OR)
      4.92, 95 per cent confidence interval 1.55 to 17.00; P = 0.008), AT below 10.2 ml
      per kg per min (OR 6.35, 1.84 to 29.80; P = 0.007), anaemia (OR 3.27, 1.04 to
      10.50; P = 0.041) and inducible cardiac ischaemia (OR 6.16, 1.48 to 23.07; P =
      0.008) were associated with 30-day mortality. Anaemia, inducible cardiac
      ischaemia and peak V.O(2) less than 15 ml per kg per min (OR 8.59, 2.33 to 55.75;
      P = 0.005) were associated with 90-day mortality on multivariable analysis.
      Patients with two or more subthreshold CPET values were at increased risk of both
      30- and 90-day mortality. CONCLUSION: An AT below 10.2 ml per kg per min, peak
      V.O(2) less than 15 ml per kg per min and at least two subthreshold CPET values
      identify patients at increased risk of early death following AAA repair.

PMID- 23001821
TI  - CPhos: a program to calculate and visualize evolutionarily conserved functional
      phosphorylation sites.
AB  - Profiling using high-throughput MS has discovered an overwhelming number of novel
      protein phosphorylation sites ("phosphosites"). However, the functional relevance
      of these sites is not always clear. In light of recent studies on the
      evolutionary mechanism of phosphorylation, we have developed CPhos, a Java
      program that can assess the conservation of phosphosites among species using an
      information theory-based approach. The degree of conservation established using
      CPhos can be used to assess the functional significance of phosphosites. CPhos
      has a user friendly graphical user interface and is available both as a web
      service and as a standalone Java application to assist phosphoproteomic
      researchers in analyzing and prioritizing lists of phosphosites for further
      experimental validation. CPhos can be accessed or downloaded at
      http://helixweb.nih.gov/CPhos/.

PMID- 23001822
TI  - Linker for activation of T-cell family member2 (LAT2) a lipid raft adaptor
      protein for AKT signaling, is an early mediator of alkylphospholipid anti
      leukemic activity.
AB  - Lipid rafts are highly ordered membrane domains rich in cholesterol and
      sphingolipids that provide a scaffold for signal transduction proteins; altered
      raft structure has also been implicated in cancer progression. We have shown that
      25 MUm 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC), an
      alkylphospholipid, targets high cholesterol domains in model membranes and
      induces apoptosis in leukemia cells but spares normal hematopoietic and
      epithelial cells under the same conditions. We performed a quantitative (SILAC)
      proteomic screening of ODPC targets in a lipid-raft-enriched fraction of leukemic
      cells to identify early events prior to the initiation of apoptosis. Six
      proteins, three with demonstrated palmitoylation sites, were reduced in
      abundance. One, the linker for activation of T-cell family member 2 (LAT2), is an
      adaptor protein associated with lipid rafts in its palmitoylated form and is
      specifically expressed in B lymphocytes and myeloid cells. Interestingly, LAT2 is
      not expressed in K562, a cell line more resistant to ODPC-induced apoptosis.
      There was an early loss of LAT2 in the lipid-raft-enriched fraction of NB4 cells
      within 3 h following treatment with 25 MUm ODPC. Subsequent degradation of LAT2
      by proteasomes was observed. Twenty-five MUm ODPC inhibited AKT activation via
      myeloid growth factors, and LAT2 knockdown in NB4 cells by shRNA reproduced this
      effect. LAT2 knockdown in NB4 cells also decreased cell proliferation and
      increased cell sensitivity to ODPC (7.5*), perifosine (3*), and arsenic trioxide
      (8.5*). Taken together, these data indicate that LAT2 is an early mediator of the
      anti-leukemic activity of alkylphospholipids and arsenic trioxide. Thus, LAT2 may
      be used as a target for the design of drugs for cancer therapy.

PMID- 23001823
TI  - Differential mechanisms of tumor progression in clones from a single
      heterogeneous human melanoma.
AB  - We used vertical growth phase (VGP) human VMM5 melanoma cells to ask whether the
      tumor microenvironment could induce matrix metalloproteinase-1 (MMP-1) in vivo,
      and whether this induction correlated with metastasis. We isolated two clones
      from parental VMM5 cells: a low MMP-1 producing clone (C4) and high producing
      clone (C9). When these clones were injected orthotopically (intradermally) into
      nude mice, both were equally tumorigenic and produced equivalent and abundant
      amounts of MMP-1. However, the tumors from the C4 clones displayed different
      growth kinetics and distinct profiles of gene expression from the C9 population.
      The C4 tumors, which had low MMP-1 levels in vitro, appeared to rely on growth
      factors and cytokines in the microenvironment to increase MMP-1 expression in
      vivo, while MMP-1 levels remained constant in the C9 tumors. C9 cells, but not C4
      cells, grew as spheres in culture and expressed higher levels of JARID 1B, a
      marker associated with melanoma initiating cells. We conclude that VMM5 melanoma
      cells exhibit striking intra-tumor heterogeneity, and that the tumorigenicity of
      these clones is driven by different molecular pathways. Our data suggest that
      there are multiple mechanisms for melanoma progression within a tumor, which may
      require different therapeutic strategies.

PMID- 23001824
TI  - Prenylated chalcone xanthohumol associates with histones in breast cancer cells-
      a novel target identified by a monoclonal antibody.
AB  - SCOPE: The intracellular fate of xanthohumol (XN) from hops is an underexplored
      field in the research for the molecular mechanisms causing its wide range of
      effects in chemoprevention and gene expression involved in hepatic metabolism.
      METHODS AND RESULTS: We aimed to elucidate possible targets for binding of XN in
      a human mammary carcinoma cell line (MCF-7/6), using a mAB. We investigated the
      overall solubility and stability of XN in growth medium and the cellular uptake
      and distribution of XN in MCF-7/6 cells using an optimized immunocytochemistry
      technique. After incubation of MCF-7/6 cells, with 10 MUM XN for 0.5 h up to 6 h,
      we observed primarily a granular nuclear staining, which intensified with
      increasing exposure times. Immunoprecipitation of cell lysates (treated with 10
      MUM XN for 2 h) revealed binding of XN to a fraction of proteins with a molecular
      weight below 20 kDa. Further analysis of the protein mixture via LC-MS/MS (Q-TOF)
      resulted in the identification of specific members of the histone family, i.e.
      histone H2A, H2B, and H4. The identity of histone H2A was confirmed using
      immunodetection with a specific anti-histone H2A antibody. CONCLUSION: In
      summary, we did successfully apply a mAB against XN in immunocytochemistry and
      precipitation with highly unexpected results.

PMID- 23001825
TI  - p-Type InP nanopillar photocathodes for efficient solar-driven hydrogen
      production.

PMID- 23001826
TI  - An unusual case of ascites.

PMID- 23001827
TI  - Expression and prognostic significance of apoptotic genes in oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity.
      Human cancers are characterized by an imbalance of regulatory mechanisms
      controlling different cellular pathways, including apoptosis. Apoptosis occurs in
      a wide variety of physiological processes, such as embryonic development, tissue
      homeostasis or immune defense, and its role is to remove harmful, damaged, or
      unwanted cells. Defective apoptosis represents an important causative factor in
      the development/progression of cancer, and the ability of tumor cells to evade
      apoptosis can play a significant role in their resistance to conventional
      anticancer treatment. We investigated the expression profile of genes involved in
      the apoptotic mechanism in 21 paired tissue samples (OSCC and adjacent normal
      oral mucosa) by cDNA macroarray, in order to identify differentially expressed
      genes in oral cancer compared to normal tissue. To validate the results obtained
      by cDNA macroarray, quantitative real-time PCR, Western blot, and
      immunohistochemical analyses were performed. Results obtained by cDNA macroarray
      analysis showed different expression levels of CRADD, FADD, ATM, APAF1, and TP63
      genes in OSCC compared to normal mucosa. Differential gene expression
      measurements (tumor vs. normal tissue) performed by real-time PCR showed an
      overexpression of FADD and a downregulation of ATM. Moreover, Western blot
      analysis confirmed that both CRADD and APAF-1 were decreased in OSCC compared to
      normal oral mucosa. As showed by immunohistochemistry, OSCC exhibited increased
      expression of p63 compared to normal tissue. Interestingly, a statistically
      significant positive correlation was found between p63 expression and the
      histological grade.

PMID- 23001829
TI  - Sangiovese and its offspring in southern Italy.
AB  - This paper demonstrates the importance of different approaches such as
      ampelography, historical researches, and molecular analysis to reveal direct
      parent-child relationship. The aim of this paper was to highlight the degree of
      relationship to five varieties spread in southern Italy, through ampelographic
      and molecular characterization: Sangiovese, Mantonico di Bianco, Gaglioppo di
      Ciro, Mantonicone, and Nerello Mascalese. Molecular characterization was carried
      out through 52 SSR molecular markers, showing that Sangiovese and Mantonico di
      Bianco are the parents of Gaglioppo di Ciro, Mantonicone, and Nerello Mascalese.
      Ampelographic description was performed using the method developed by the
      Organisation Internationale de la Vigne et du Vin. This analysis identifies three
      distinct groups: the first brings together Sangiovese and the two offspring
      Nerello Mascalese and Gaglioppo di Ciro, while Mantonico di Bianco and
      Mantonicone are positioned at a distance from the first and between them. Using
      molecular characterization, supported by the ampelographic one, we showed that
      Gaglioppo di Ciro, Mantonicone, and Nerello Mascalese, three varieties recovered
      in the southern regions of Italy, such as Calabria and Sicily, originated by the
      cross between a nationally spread grape variety as Sangiovese and a Calabria
      autochthonous vine as Mantonico di Bianco.

PMID- 23001830
TI  - Impacts of composition and post-treatment on the Bronsted acidity of steam
      treated faujasite: insights from FTIR spectroscopy.
AB  - A detailed FTIR study of the effects of steaming and acid leaching on protonated
      Y faujasite (FAU) and EMT zeolites is provided and the results are thoroughly
      analysed. In particular, emphasis is placed on the Bronsted acidic evolution and
      acidic strength measurements for a large series of as-modified zeolites using CO
      as a sensitive probe to distinguish various protonic sites. While an increase of
      acidity for framework OH groups is observed during the strengthening of
      dealumination for both FAU and EMT series, the steaming process also generates a
      large variety of additional Bronsted acidic groups. Regarding acidic strength,
      these heterogeneous OH groups are sensitive to post-treatments and their
      existence strongly depends on the initial composition of the zeolites. The
      presence of residual Na(+) cations in the starting materials induces dramatic
      Bronsted acidic changes after steaming. As a result, steamed zeolites that
      initially contain traces of sodium possess unusual acidic Bronsted groups with
      low acidity. This result contradicts the trend generally observed with framework
      OH groups, for which steaming results in an increase of Bronsted acidic strength.
      The study reveals that the situation is indeed more complex, as some compositions
      and post-treatments strongly influence the Bronsted acidity of as-steamed
      zeolites both in their nature and their corresponding acidic strength. By linking
      these IR-compiled features to the as-exposed modifications, a large acidity scale
      better suited to characterizing catalysts having Bronsted acidity expanding from
      lowest to highest strength is proposed.

PMID- 23001828
TI  - In vivo diffusion tensor MRI of the human heart: reproducibility of breath-hold
      and navigator-based approaches.
AB  - The aim of this study was to implement a quantitative in vivo cardiac diffusion
      tensor imaging (DTI) technique that was robust, reproducible, and feasible to
      perform in patients with cardiovascular disease. A stimulated-echo single-shot
      echo-planar imaging (EPI) sequence with zonal excitation and parallel imaging was
      implemented, together with a novel modification of the prospective navigator
      (NAV) technique combined with a biofeedback mechanism. Ten volunteers were
      scanned on two different days, each time with both multiple breath-hold (MBH) and
      NAV multislice protocols. Fractional anisotropy (FA), mean diffusivity (MD), and
      helix angle (HA) fiber maps were created. Comparison of initial and repeat scans
      showed good reproducibility for both MBH and NAV techniques for FA (P > 0.22), MD
      (P > 0.15), and HA (P > 0.28). Comparison of MBH and NAV FA (FAMBHday1 = 0.60 +/-
      0.04, FANAVday1 = 0.60 +/- 0.03, P = 0.57) and MD (MDMBHday1 = 0.8 +/- 0.2 * 10(
      3) mm(2) /s, MDNAVday1 = 0.9 +/- 0.2 * 10(-3) mm(2) /s, P = 0.07) values showed
      no significant differences, while HA values (HAMBHday1Endo = 22 +/- 10 degrees ,
      HAMBHday1Mid-Endo = 20 +/- 6 degrees , HAMBHday1Mid-Epi = -1 +/- 6 degrees ,
      HAMBHday1Epi = -17 +/- 6 degrees , HANAVday1Endo = 7 +/- 7 degrees , HANAVday1Mid
      Endo = 13 +/- 8 degrees , HANAVday1Mid-Epi = -2 +/- 7 degrees , HANAVday1Epi = 
      14 +/- 6 degrees ) were significantly different. The scan duration was 20% longer
      with the NAV approach. Currently, the MBH approach is the more robust in normal
      volunteers. While the NAV technique still requires resolution of some bulk motion
      sensitivity issues, these preliminary experiments show its potential for in vivo
      clinical cardiac diffusion tensor imaging and for delivering high-resolution in
      vivo 3D DTI tractography of the heart.

PMID- 23001832
TI  - Motivational interventions in the eating disorders: what is the evidence?
AB  - BACKGROUND: Eating disorder treatments are plagued by poor engagement and high
      drop-out. People who disengage from eating disorder treatment appear poorly
      motivated to change, and may benefit from adaptations of Motivational
      Interviewing (AMIs). OBJECTIVE: To investigate whether the use of interventions
      specifically designed to enhance motivation in the eating disorders is supported
      empirically. METHOD: Literature was reviewed for relevant studies. RESULTS: Eight
      studies have investigated the efficacy of AMIs. AMIs improve motivation to change
      bingeing and reduce actual bingeing behavior. There was little support for AMIs
      for compensatory or restrictive behaviors. There was mixed evidence that AMIs may
      improve motivation, but little to suggest they are more effective than other
      approaches. DISCUSSION: The widespread interest in using motivational approaches
      in the eating disorders is not strongly supported by the literature. The current
      evidence base does not support the widespread dissemination of motivation
      enhancing interventions in the eating disorders.

PMID- 23001833
TI  - Nodal recovery, dual pathway physiology, and concealed conduction determine
      complex AV dynamics in human atrial tachyarrhythmias.
AB  - The genesis of complex ventricular rhythms during atrial tachyarrhythmias in
      humans is not fully understood. To clarify the dynamics of atrioventricular (AV)
      conduction in response to a regular high-rate atrial activation, 29 episodes of
      spontaneous or pacing-induced atrial flutter (AFL), covering a wide range of
      atrial rates (cycle lengths from 145 to 270 ms), were analyzed in 10 patients. AV
      patterns were identified by applying firing sequence and surrogate data analysis
      to atrial and ventricular activation series, whereas modular simulation with a
      difference-equation AV node model was used to correlate the patterns with
      specific nodal properties. AV node response at high atrial rate was characterized
      by 1) AV patterns of decreasing conduction ratios at the shortening of atrial
      cycle length (from 236.3 +/- 32.4 to 172.6 +/- 17.8 ms) according to a Farey
      sequence ordering (conduction ratio from 0.34 +/- 0.12 to 0.23 +/- 0.06; P <
      0.01); 2) the appearance of high-order alternating Wenckebach rhythms, such as
      6:2, 10:2, and 12:2, associated with ventricular interval oscillations of large
      amplitude (407.7 +/- 150.4 ms); and 3) the deterioration of pattern stability at
      advanced levels of block, with the percentage of stable patterns decreasing from
      64.3 +/- 35.2% to 28.3 +/- 34.5% (P < 0.01). Simulations suggested these patterns
      to originate from the combined effect of nodal recovery, dual pathway physiology,
      and concealed conduction. These results indicate that intrinsic nodal properties
      may account for the wide spectrum of AV block patterns occurring during regular
      atrial tachyarrhythmias. The characterization of AV nodal function during
      different AFL forms constitutes an intermediate step toward the understanding of
      complex ventricular rhythms during atrial fibrillation.

PMID- 23001831
TI  - Gastric peptides and their regulation of hunger and satiety.
AB  - Ingestion of food affects the secretion of hormones from specialized endocrine
      cells scattered within the intestinal mucosa. Upon release, these hormones mostly
      decrease food intake by signaling information to the brain. Although
      enteroendocrine cells in the small intestine were thought to represent the
      predominant gut-brain regulators of food intake, recent advances also established
      a major role for gastric hormones in these regulatory pathways. First and
      foremost, the gastric endocrine X/A-like cell was in the focus of many studies
      due to the production of ghrelin, which is until now the only known orexigenic
      hormone that is peripherally produced and centrally acting. Although X/A-cells
      were initially thought to only release one hormone that stimulates food intake,
      this view has changed with the identification of additional peptide products also
      derived from this cell, namely desacyl ghrelin, obestatin, and nesfatin-1.
      Desacyl ghrelin may play a counter-regulatory role to the food intake stimulatory
      effect of ghrelin. The same property was suggested for obestatin; however, this
      hypothesis could not be confirmed in numerous subsequent studies. Moreover, the
      description of the stomach as the major source of the novel anorexigenic hormone
      nesfatin-1 derived from the NUCB2 gene further corroborated the assumption that
      the gastric X/A-like cell products are not only stimulant but also inhibitors of
      feeding, thereby acting as so far unique dual regulator of food intake located in
      a logistically important place where the gastrointestinal tract has initial
      contact with food.

PMID- 23001834
TI  - Comparison between adenosine and isoflurane for assessing the coronary flow
      reserve in mouse models of left ventricular pressure and volume overload.
AB  - Adenosine and high-concentration isoflurane are commonly used to induce hyperemia
      for assessment of coronary flow reserve (CFR) in mice, but high-concentration
      isoflurane may exacerbate cardiac dysfunction, leading to impaired CFR. However,
      there is no study be found comparing the effects of adenosine and isoflurane on
      CFR and corresponding cardiac function. High-resolution echocardiography and
      invasive hemodynamic assessment were performed in 20 mice 2 wk after transverse
      aortic constriction (TAC), aortic regurgitation (AR), and corresponding sham
      operation. CFR was calculated as the ratio of hyperemic to basal peak diastolic
      velocity (CFRpdv) or diastolic velocity-time integral (CFRdvti). In the sham
      operated mice, no differences were observed between the effects of adenosine and
      isoflurane on CFR, left ventricular systolic function (left ventricular ejection
      fraction and fractional shortening), left ventricular end-systolic pressure,
      maximal contraction and relaxation velocity (+dp/dt and -dp/dt), alteration of
      left ventricular pressure (DeltaLVP), or +/-dp/dt (Deltadp/dt). But adenosine
      derived results were significantly higher than isoflurane-derived ones in both
      the TAC and the AR groups. Moreover, CFRpdv or CFRdvti was positively correlated
      with both LVEF and LVFS. Compared with adenosine-derived CFR, isoflurane-derived
      CFR may be underestimated in the TAC and the AR mice, which is probably
      associated with suppressed cardiac function.

PMID- 23001836
TI  - Myocardial cell sheet therapy and cardiac function.
AB  - Heart failure (HF) is the leading cause of death in developed countries.
      Regenerative medicine has the potential to drastically improve treatment for
      advanced HF. Stem cell-based medicine has received attention as a promising
      candidate therapy over the past decade; however, it has not yet realized this
      potential in terms of reliability. The cell sheet is an innovative technology for
      constructing aligned graft cells, and several cell sources have been investigated
      for making a feasible cell sheet. The most representative thus far is skeletal
      myoblast, although such cells raise the issue of arrhythmogenicity. Regenerative
      cardiomyocytes (CMs) derived from pluripotent stem cells (PSCs), such as
      embryonic stem cells or induced PSCs, are the most promising, because a
      myocardial cell sheet (MCS) constructed with regenerative CMs can potentially
      enable contraction recovery and electromechanical coupling with host CMs. The
      functional outcomes of experimental MCS are reduction of ventricular wall stress
      and paracrine effects rather than contraction recovery. Several technical
      obstacles still hamper the clinical application of MCSs, with graft survival the
      most pivotal issue. Ischemia, apoptosis, inflammation, and immune response can
      all cause graft cell death, and a stable blood supply to the MCS is critical for
      successful engraftment. Ventricular tachycardia must also be considered in any
      myocardial cell therapy, and multiple layering of MCS (>3 layers) is necessary to
      reconstruct human myocardium. Innervation is also a potential issue. The future
      application of myocardial cell therapy with MCS for advanced HF depends on
      resolving these difficulties.

PMID- 23001837
TI  - Progression of myocardial remodeling and mechanical dysfunction in the
      spontaneously hypertensive rat.
AB  - The progression of hypertensive heart disease (HHD) to heart failure (HF) is
      associated with myocardial remodeling. Corresponding changes in three-dimensional
      organization of cardiac extracellular matrix have not been quantified or related
      fully to the development of HF. Spontaneously hypertensive rats (SHRs) and Wistar
      Kyoto controls were studied at 3, 12, 18, and 24 mo. Hemodynamic and
      morphological data, brain natriuretic peptide levels, and echocardiography
      demonstrate four distinct disease stages: systemic hypertension, diastolic
      dysfunction, early systolic failure, and decompensated HF. Passive left
      ventricular (LV) pressure-volume relationships were determined in vitro.
      Transmural specimens from the anterior LV free wall were imaged using extended
      volume confocal microscopy, and three-dimensional myocardial architecture was
      quantified. In SHRs, LV compliance was reduced at 12 mo and increased
      progressively thereafter. However, it was less than in controls for filling
      pressures <10 mmHg and not significantly different at >=10 mmHg. Myocyte cross
      section was enlarged, with increased variability from 12 mo, while collagen
      fraction increased progressively. Perimysial collagen fraction remained unchanged
      with age, although endomysial collagen increased from 12 mo. Perimysial collagen
      between adjacent muscle layers fused at 12 mo and continued to thicken
      subsequently, while muscle layers became more dispersed and disordered. We
      conclude that LV dilatation, which accompanies decompensated HF in this model of
      HHD, is not due to LV "softening." While perimysial (and endomysial) collagen
      networks are substantially remodeled, they are not dissolved, as has been
      proposed. We argue that progressive disruption of the laminar organization of LV
      myocardium may contribute to impaired systolic function in HHD.

PMID- 23001835
TI  - Histamine induces activation of protein kinase D that mediates tissue factor
      expression and activity in human aortic smooth muscle cells.
AB  - Histamine, an inflammatory mediator, has been shown to influence the pathogenesis
      of vascular wall cells. However, the molecular basis of its influence is not well
      understood. Our data reveal that histamine markedly induces protein kinase D
      (PKD) activation in human aortic smooth muscle cells. PKD belongs to a family of
      serine/threonine protein kinases, and its function in vascular disease is largely
      unknown. Our data show that histamine-induced PKD phosphorylation is dependent on
      the activation of histamine receptor 1 and protein kinase C (PKC). To determine
      the role of PKD in the histamine pathway, we employed a small-interfering RNA
      approach to downregulate PKD expression and found that PKD1 and PKD2 are key
      mediators for expression of tissue factor (TF), which is the key initiator of
      blood coagulation and is important for thrombosis. Our results show that PKD2
      predominantly mediates histamine-induced TF expression via the p38 mitogen
      activated protein kinase (MAPK) pathway, whereas PKD1 mediates histamine-induced
      TF expression through a p38 MAPK-independent pathway. We demonstrate that
      histamine induces TF expression via the PKC-dependent PKD activation. Our data
      provide the first evidence that PKD is a new component in histamine signaling in
      live cells and that PKD has a novel function in the histamine signaling pathway
      leading to gene expression, as evidenced by TF expression. Importantly, our data
      reveal a regulatory link from histamine to PKD and TF, providing new insights
      into the mechanisms of coagulation and the development of atherothrombosis.

PMID- 23001838
TI  - From alkyl aromatics to aromatic esters: efficient and selective C-H activation
      promoted by a bimetallic heterogeneous catalyst.
AB  - Oxidizing aromatics: We report an operationally simple and green catalytic
      oxidative esterification approach that selectively converts methyl aromatics to
      aromatic carboxylates utilizing a highly stable, active, and reusable
      heterogeneous bimetallic Au-Pd catalyst and molecular oxygen as benign oxidant
      without requiring any additives.

PMID- 23001839
TI  - Progress and challenges in improving surgical outcomes.

PMID- 23001840
TI  - Treg cells in giant cell arteritis: might they be another target for adjuvant
      treatment? Comment on the article by Samson et al. Reply.

PMID- 23001841
TI  - Altered maternal left ventricular contractility and function during normal
      pregnancy.
AB  - OBJECTIVES: To evaluate maternal left ventricular (LV) systolic and diastolic
      function during normal pregnancy by non-invasive measures of LV contractility
      incorporating loading conditions. METHODS: Sixty-five women were examined using
      echocardiography, including tissue Doppler and two-dimensional speckle tracking,
      and subclavian artery pulse trace recordings at gestational weeks 14-16, 22-24
      and 36, and at 6 months postpartum. RESULTS: The mean +/- SD age of the women was
      32.0 +/- 4.6 years. Cardiac output and LV end-diastolic volume were on average
      20% and 23% higher, respectively, during pregnancy, compared to that at 6 months
      postpartum (both, P < 0.01). LV ejection fraction, global peak systolic strain
      and rate-corrected LV velocity of circumferential fiber shortening (Vcfc) were
      11%, 6% and 6% lower, respectively, at 36 weeks' gestation compared to at 6
      months postpartum (all, P < 0.01). Afterload, measured as LV end-systolic wall
      stress (ESWS) increased by 10% between 14-16 and 36 weeks' gestation (P < 0.01).
      Analysis of the relationship between Vcfc and ESWS revealed that LV contractility
      was lower during pregnancy than at 6 months postpartum. Changes in diastolic
      function were demonstrated by 11% lower mitral early diastolic (E) wave velocity,
      8% lower tissue Doppler early diastolic velocity (e') and 13% higher left atrial
      area (all P < 0.01) during pregnancy. Tissue Doppler E/e' remained unaltered (P =
      0.78). CONCLUSIONS: During normal pregnancy, LV contractility is lower than it is
      at 6 months postpartum. This is associated with increased LV and left atrial
      area, whereas filling pressures are unchanged. These findings suggest that
      pregnancy exerts a larger load on the cardiovascular system than previously
      assumed.

PMID- 23001843
TI  - Picking up 30 CO2 molecules by a porous metal oxide capsule based on the same
      number of receptors.
AB  - 30 receptors in waiting position: In the porous (pentagon)(12)(linker)(30)-type
      molybdenum oxide capsule (see picture), the 30 positively charged linkers (five
      unsaturated shown for illustration in green, the others contain CO(3)(2-)
      ligands) can act as receptors for neutral and negatively charged ligands.
      Bubbling CO(2) into the solution containing the acetate-type capsules leads to
      the upload of CO(2) based on 30 coordinated CO(3)(2-) ligands.

PMID- 23001842
TI  - A new method for quantitative analysis of cell surface glycoproteome.
AB  - As the altered glycosylation expressions of cell surface proteins are associated
      with many diseases, glycoproteomics approach has been widely applied to
      characterization of surface glycosylation alteration. In general, the abundances
      of proteolytic glycopeptides derived from corresponding glycoproteins can be
      measured to determine the abundances of glycoproteins. However, this
      quantification strategy cannot distinguish whether the changes are results from
      changes of protein abundance or changes in glycosite occupancy. For the accurate
      and specific quantification of the cell surface glycosylation profile, we
      proposed a modified cell surface-capturing strategy where the glycopeptides were
      submitted to LC-MS/MS analysis directly for identification of glycoproteins and
      the non-glycopeptides were isotopically labelled for quantification of
      glycoproteins. This strategy was applied to comparatively analyze cell surface
      glycoproteins of two human cell lines, i.e. Chang Liver and HepG2 cells. Totally
      341 glycoproteins were identified with 82.4% specificity for cell membrane
      proteins and 33 glycoproteins were quantified with significant expression change
      between the two cell lines. The differential expressions of two selected proteins
      (EMMPRIN and BCAM) were validated by Western blotting. This method enables
      specific and accurate analysis of the cell surface glycoproteins and may have
      broad application in the field of biomarker and drug target discovery.

PMID- 23001844
TI  - Exogenous hydrogen sulfide attenuates diabetic myocardial injury through cardiac
      mitochondrial protection.
AB  - In the study, we investigated how exogenous H(2)S (hydrogen sulfide) influenced
      streptozotocin (STZ)-induced diabetic myocardial injury through cardiac
      mitochondrial protection and nitric oxide (NO) synthesis in intact rat hearts and
      primary neonatal rat cardiomyocytes. Diabetes was induced by STZ (50 mg/kg) and
      the daily administration of 100 MUM NaHS (sodium hydrosulfide, an H(2)S donor) in
      the diabetes + NaHS treatment group. At the end of 4, 8, and 12 weeks, the
      morphological alterations and functions of the hearts were observed using
      transmission electron microscopy and echocardiography system. The percentage of
      apoptotic cardiomyocytes, the mitochondrial membrane potential, the production of
      reactive oxygen species (ROS) and the level of NO were measured. The expressions
      of cystathionine-gamma-lyase (CSE), caspase-3 and -9, the mitochondrial NOX4 and
      cytochrome c were analyzed by western blotting. The results showed the cardiac
      function injured, morphological changes and the apoptotic rate increased in the
      diabetic rat hearts. In the primary neonatal rat cardiomyocytes of high glucose
      group, ROS production was increased markedly, whereas the expression of CSE and
      the level of NO was decreased. However, treatment with NaHS significantly
      reversed the diabetic rat hearts function, the morphological changes and
      decreased the levels of ROS and NO in the primary neonatal rat cardiomyocytes
      administrated with high glucose group. Furthermore, NaHS down-regulated the
      expression of mitochondrial NOX4 and caspase-3 and -9 and inhibited the release
      of cytochrome c from mitochondria in the primary neonatal rat cardiomyocytes. In
      conclusion, H(2)S is involved in the attenuation of diabetic myocardial injury
      through the protection of cardiac mitochondria.

PMID- 23001845
TI  - ATF4 and IRE1alpha inhibit DNA repair protein DNA-dependent protein kinase 1
      induced by heat shock.
AB  - With the increase of environment temperature, more and more attentions are payed
      to the effects of heat stress. Cells under heat shock either are adapted to the
      condition or are damaged and dead. In this paper, we found that heat shock
      induced endoplasmic reticulum (ER) stress. ATF4, PERK, and IRE1alpha were induced
      by heat shock of 45  degrees C in the transcriptional level. Under the stress of
      45  degrees C, PERK was phosphorylated and XBP1s was detected. The result
      indicated that heat shock could induce the ER stress. We found that heat shock of
      45  degrees C induced the dysregulation of HSP70 and DNA-PKcs, and downregulated
      the expression of PARP1 and XRCC1. Further results showed that after the
      knockdown of ATF4 or IRE1alpha, the expression of DNA-PKcs and XRCC1 were
      increased. It was indicated that ATF4 and IRE1alpha could inhibit the expression
      of DNA-PKcs and XRCC1 under the heat stress. Our results suggested that heat
      shock could activate ER stress. IRE1alpha and ATF4, as the important ER stress
      molecules, could inhibit the expression of DNA repair proteins DNA-PKcs, XRCC1,
      and HSP70 under heat shock. Downregulation of DNA repair proteins could aggravate
      the cell damage that may cause cell apoptosis. This may explain that heat shock
      could increase the lethality of chemotherapeutic drugs on tumor cells.

PMID- 23001846
TI  - HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway.
AB  - Chronic hepatitis B virus infection is the dominant global cause of
      hepatocellular carcinoma (HCC), especially hepatitis B virus-X (HBx) plays a
      major role in this process. HBx protein promotes cell cycle progression,
      inactivates negative growth regulators, and binds to and inhibits the expression
      of p53 tumor suppressor gene and other tumor suppressor genes and senescence
      related factors. However, the relationship between HBx and autophagy during the
      HCC development is poorly known. Previous studies found that autophagy functions
      as a survival mechanism in liver cancer cells. We suggest that autophagy plays a
      possible role in the pathogenesis of HBx-induced HCC. The present study showed
      that HBx transfection brought about an increase in the formation of
      autophagosomes and autolysosomes. Microtubule-associated protein light chain 3,
      Beclin 1, and lysosome-associated membrane protein 2a were up-regulated after HBx
      transfection. HBx-induced increase in the autophagic level was increased by mTOR
      inhibitor rapamycin and was blocked by treatment with the PI3K-Akt inhibitor
      LY294002. The same results can also be found in HepG2.2.15 cells. These results
      suggest that HBx activates the autophagic lysosome pathway in HepG-2 cells
      through the PI3K-Akt-mTOR pathway.

PMID- 23001848
TI  - Graphene: a reusable substrate for unprecedented adsorption of pesticides.
AB  - Unprecedented adsorption of chlorpyrifos (CP), endosulfan (ES), and malathion
      (ML) onto graphene oxide (GO) and reduced graphene oxide (RGO) from water is
      reported. The observed adsorption capacities of CP, ES, and ML are as high as
      ~1200, 1100, and 800 mg g(-1) , respectively. Adsorption is found to be
      insensitive to pH or background ions. The adsorbent is reusable and can be
      applied in the field with suitable modifications. A first-principles
      pseudopotential-based density functional analysis of graphene-water-pesticide
      interactions showed that the adsorption is mediated through water, while direct
      interactions between graphene and the pesticides is rather weak or unlikely.

PMID- 23001847
TI  - PI3 kinase/Akt/HIF-1alpha pathway is associated with hypoxia-induced epithelial
      mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis.
AB  - Migration and invasion of fibroblast-like synoviocytes (FLSs) are critical in the
      pathogenesis of rheumatoid arthritis (RA). Hypoxic conditions are present in RA
      joints, and hypoxia has been extensively studied in angiogenesis and
      inflammation. However, its effect on the migration and invasion of RA-FLSs
      remains unknown. In this study, we observed that RA-FLSs exposed to hypoxic
      conditions experienced epithelial-mesenchymal transition (EMT), with increased
      cell migration and invasion. We demonstrated that hypoxia-induced EMT was
      accompanied by increased hypoxia-inducible factor (HIF)-1alpha expression and
      activation of Akt. After knockdown or inhibition of HIF-1alpha in hypoxia by
      small interfering RNA or genistein (Gen) treatment, the EMT transformation and
      invasion ability of FLSs were regained. HIF-1alpha could be blocked by
      phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, indicating that HIF
      1alpha activation was regulated by the PI3K/Akt pathway. Administration of
      LY294002 (20 mg/kg, intra-peritoneally) twice weekly and Gen (25 mg/kg, by
      gavage) daily for 3 weeks from day 20 after primary immunization in a collagen
      induced arthritis rat model, markedly alleviated the clinical signs, radiology
      progression, synovial hyperplasia, and inflammatory cells infiltration of joints.
      Thus, results of this study suggest that activation of the PI3K/Akt/HIF-1alpha
      pathway plays a pivotal role in mediating hypoxia-induced EMT transformation and
      invasion of RA-FLSs under hypoxia.

PMID- 23001850
TI  - Sociocultural factors in the development of bulimia nervosa in a blind woman: a
      case report.
AB  - BACKGROUND: Although several cases of eating disorders in visually impaired women
      have been reported, there has been little research on the development of body
      image and disordered eating in the blind. Overall, it is argued that blind women
      are protected from developing body dissatisfaction because of having had little
      or no exposure to thin-ideal images, and that if they do develop an eating
      disorder, this would be linked to other risk factors. In the one reported case of
      bulimia nervosa in a blind woman, body image concerns were even absent. METHOD:
      We report a single case of bulimia nervosa in a 28-year-old congenitally blind
      woman whose presentation was typical, including body dissatisfaction and drive
      for thinness. DISCUSSION: The present case underscores the need to also consider
      an etiological role of perceived sociocultural pressure and thin-ideal
      internalization in promoting body dissatisfaction and eating disorders in
      visually impaired women.

PMID- 23001849
TI  - Inhibition of NF-kappaB activity by HIV-1 Vpr is dependent on Vpr binding
      protein.
AB  - Numerous studies have reported that Vpr alters NF-kappaB signaling in various
      cell types, however, the findings have been largely conflicting with reports of
      both stimulatory and inhibitory effects of Vpr. Our aim was to investigate the
      role of Vpr signaling in myeloid cells using an adenovirus based expression and
      indicator system. Our results show that Vpr is inhibitory to NF-kappaB, however,
      this effect is dependent on the particular manner of NF-kappaB stimulation.
      Consistent with this notion, we report that Vpr has inhibitory effects that are
      specific to the TNF-alpha pathway, but not affecting the LPS pathway, suggesting
      that differential targets of Vpr may exist for NF-kappaB regulation. Further, we
      identify VprBP as one possible cellular component of Vpr's regulation of
      IkappaBalpha in response to TNF-alpha stimulation. We did not identify such a
      role for HSP27, which instead seems to inhibit Vpr functions. Chronically HIV-1
      infected U1 cells with knockdown constructs for Vpr were unexpectedly less
      responsive to TNF-alpha mediated viral replication, perhaps suggesting that other
      HIV-1 components may antagonize these anti-NF-kappaB effects in infected cells.
      We hypothesize that Vpr may serve an important role in the context of viral
      infection and immune function in vivo, through its selective inhibition of NF
      kappaB pathways.

PMID- 23001851
TI  - Effects of curcumin on bleomycin-induced apoptosis in human malignant testicular
      germ cells.
AB  - Testicular cancer is the most common cancer among young men of reproductive age.
      Bleomycin is a frequently used drug for the treatment of several malignancies and
      is part of the chemotherapy protocols in testicular cancer. Bleomycin causes an
      increase in oxidative stress which has been shown to induce apoptosis in cancer
      cells. Curcumin (diferuloylmethane), an active component of the spice turmeric,
      has attracted interest because of its anti-inflammatory and chemopreventive
      activities. However, no study has been carried out so far to elucidate its
      interaction with bleomycin in testicular cancer cells. In this study, we
      investigated the effects of curcumin and bleomycin on apoptosis signalling
      pathways and compared the effects of bleomycin with H2O2 which directly produces
      reactive oxygen species. We measured apoptosis markers such as caspase-3, caspase
      8, and caspase-9 activities and Bcl-2, Bax, and Cyt-c levels in NCCIT cells
      incubated with curcumin (5 MUM), bleomycin (120 MUg/ml), bleomycin + curcumin,
      H2O2 (35 MUM), and H2O2 + curcumin for 72 h. Curcumin, bleomycin, and H2O2 caused
      apoptosis indicated as increases in caspase-3, caspase-8, and caspase-9
      activities and Bax and cytoplasmic Cyt-c levels and a decrease in Bcl-2 level.
      Concurrent use of curcumin with bleomycin decreased caspase activities and Bax
      and Cyt-c levels compared to their separate effects in NCCIT cells. Our findings
      suggest that concurrent use of curcumin during chemotherapy in testis cancer
      should be avoided due to the inhibitory effect of curcumin on bleomycin-induced
      apoptosis.

PMID- 23001852
TI  - Wideband MR elastography for viscoelasticity model identification.
AB  - The growing clinical use of MR elastography requires the development of new
      quantitative standards for measuring tissue stiffness. Here, we examine a soft
      tissue mimicking phantom material (Ecoflex) over a wide frequency range (200 Hz
      to 7.75 kHz). The recorded data are fit to a cohort of viscoelastic models of
      varying complexity (integer and fractional order). This was accomplished using
      multiple sample sizes by employing geometric focusing of the shear wave front to
      compensate for the changes in wavelength and attenuation over this broad range of
      frequencies. The simple axisymmetric geometry and shear wave front of this
      experiment allows us to calculate the frequency-dependent complex-valued shear
      modulus of the material. The data were fit to several common models of linear
      viscoelasticity, including those with fractional derivative operators, and we
      identified the best possible matches over both a limited frequency band (often
      used in clinical studies) and over the entire frequency span considered. In
      addition to demonstrating the superior capability of the fractional order
      viscoelastic models, this study highlights the advantages of measuring the
      complex-valued shear modulus over as wide a range of frequencies as possible.

PMID- 23001853
TI  - Involvement of annexin A8 in the properties of pancreatic cancer.
AB  - Although Annexin A8 (ANXA8), a member of a superfamily of calcium and
      phospholipid binding proteins, is physiologically expressed in a tissue-specific
      manner, recent microarray studies reported that ANXA8 was also ectopically
      expressed in pancreatic cancers. We investigated the molecular mechanism of
      expression of ANXA8 in cancer cells and its functional role in pancreatic cancer
      cells. ANXA8 was diversely expressed in human cancer cell lines. Expression was
      enhanced by treatment with 5-aza-dC and butyrate, and correlated with methylation
      status at CpG in the promoter-exon 1 region. Inhibition of ANXA8 using siRNA in
      BxPC-3 cells which express ANXA8 at a high level elevated caspase-3 and -7
      activities. In in vitro invasion assay, inhibition of ANXA8 using siRNA in BxPC-3
      reduced the numbers of migrating cells, and down-regulated HIF-1alpha mRNA
      transcription. Overexpression of ANXA8 increased the number of viable cells and
      BrdU incorporation in PANC-1 cells, which express ANXA8 at a low level.
      Expression of ANXA8 was induced under conditions of nutrient deprivation, and
      overexpression of ANXA8 showed resistance against serum starvation in PANC-1
      cells. In a promoter assay, co-transfection with the expression vector of ANXA8
      and the vector of a reporter gene containing the promoter of HIF-1alpha enhanced
      HIF-1alpha promoter activity. In contrast, this effect of ANXA8 was inhibited by
      administration of BAPTA-AM, an intracellular Ca2+ chelator. These results suggest
      that ectopic ANXA8 expression in cancer cells might involve an epigenetic
      mechanism. ANXA8 might play an important role in calcium fluctuation-mediated HIF
      1alpha transcriptional activation and cell viability.

PMID- 23001854
TI  - Site-directed mutations of the gatekeeping loop region affect the activity of
      Escherichia coli spermidine synthase.
AB  - Spermidine synthase catalyzes the production of spermidine from putrescine and
      decarboxylated S-adenosylmethionine (dcSAM), and plays a crucial role in cell
      proliferation and differentiation. The gatekeeping loop identified in the
      structure of spermidine synthase was predicted to contain residues important for
      substrate binding, but its correlation with enzyme catalysis has not been fully
      understood. In this study, recombinant Escherichia coli spermidine synthase
      (EcSPDS) was produced and its enzyme kinetics was characterized. Site-directed
      mutants of EcSPDS were obtained to demonstrate the importance of the amino acid
      residues in the gatekeeping loop. Substitution of Asp158 and Asp161 with alanine
      completely abolished EcSPDS activity, suggesting that these residues are
      absolutely required for substrate interaction. Reduction in enzyme activity was
      observed in the C159A, T160A, and P165Q variants, indicating that hydrophobic
      interactions contributed by Cys159, Thr160, and Pro165 are important for enzyme
      catalysis as well. On the other hand, replacement of Pro162 and Ile163 had no
      influence on EcSDPS activity. These results indicate that residues in the
      gatekeeping loop of spermidine synthase are indispensable for the catalytic
      reaction of EcSPDS. To the best of our knowledge, this is the first functional
      study on the gatekeeping loop of EcSPDS by site-directed mutagenesis.

PMID- 23001855
TI  - Build a two-way road for health industry: the current circumstance of
      translational medicine in China.

PMID- 23001856
TI  - Prism-based surface plasmon coupled emission imaging.
AB  - A prism-based surface plasmon coupled emission (SPCE) imaging apparatus with a
      reverse Kretschmann (RK) configuration was developed and applied to dye-doped
      polymer films. Highly polarized, directional and enhanced fluorescence images
      were obtained. The angular distribution of the SPCE images was in accordance with
      the validated theoretical calculation performed using Fresnel equation. Prism
      based SPCE imaging combined with microarray technology appears to be a promising
      platform for rapid and high-throughput analysis, especially for high-density
      arrays. We believe that prism-based SPCE imaging has potential applications in
      biochemical research.

PMID- 23001857
TI  - Endoscopic ultrasonographic assessment of gastric polyps and endoscopic mucosal
      resection.
AB  - Gastric polyps refer to a heterogeneous group of epithelial- and subepithelial
      based lesions that vary in histology and malignant potential. Although many
      gastric polyps have characteristic endoscopic appearances, their diagnosis,
      classification, and potential for malignant transformation are based on
      histologic evaluation. Therefore, all types of gastric polyps should be biopsied
      during the incident endoscopy. Mucosal-based polyps include fundic gland polyps,
      hyperplastic polyps, adenomatous polyps, and hamartomatous polyps. Inflammatory
      fibroid polyps may endoscopically appear similar to mucosal-based polyps but
      actually arise from the submucosa. Certain types of polyps are associated with
      genetic syndromes or potential precancerous conditions (gastric intestinal
      metaplasia and chronic atrophic gastritis). If dysplasia is present and the polyp
      is >=2 cm or symptomatic, the polyp should be endoscopically resected with the
      aim of en bloc resection. There are limited data on the use of adjunctive
      endoscopic ultrasound (EUS) in the evaluation of mucosal-based gastric polyps,
      and therefore, is not routinely employed in the management of these lesions. EUS
      is recommended for the evaluation of gastric subepithelial lesions.

PMID- 23001858
TI  - Frequency of surveillance scanning in pediatric Hodgkin disease can safely be
      reduced.

PMID- 23001860
TI  - Treg cells in giant cell arteritis: might they be another target for adjuvant
      treatment? Comment on the article by Samson et al.

PMID- 23001859
TI  - N-terminal protein processing: a comparative proteogenomic analysis.
AB  - N-terminal methionine excision (NME) and N-terminal acetylation (NTA) are two of
      the most common protein post-translational modifications. NME is a universally
      conserved activity and a highly specific mechanism across all life forms. NTA is
      very common in eukaryotes but occurs rarely in prokaryotes. By analyzing data
      sets from yeast, mammals and bacteria (including 112 million spectra from 57
      bacterial species), the largest comparative proteogenomics study to date, it is
      shown that previous assumptions/perceptions about the specificity and purposes of
      NME are not entirely correct. Although NME, through the universal enzymatic
      specificity of the methionine aminopeptidases, results in the removal of the
      initiator Met in proteins when the second residue is Gly, Ala, Ser, Cys, Thr,
      Pro, or Val, the comparative genomic analyses suggest that this specificity may
      vary modestly in some organisms. In addition, the functional role of NME may be
      primarily to expose Ala and Ser rather than all seven of these residues. Although
      any of this group provide "stabilizing" N termini in the N-end rule, and de facto
      leave the remaining 13 amino acid types that are classed as "destabilizing" (in
      higher eukaryotes) protected by the initiator Met, the conservation of NME
      substrate proteins through evolution suggests that the other five are not
      crucially important for proteins with these residues in the second position. They
      are apparently merely inconsequential players (their function is not affected by
      NME) that become exposed because their side chains are smaller or comparable to
      those of Ala and Ser. The importance of exposing mainly two amino acids at the N
      terminus, i.e. Ala and Ser, is unclear but may be related to NTA or other post
      translational modifications. In this regard, these analyses also reveal that NTA
      is more prevalent in some prokaryotes than previously appreciated.

PMID- 23001861
TI  - Protein interactomics based on direct molecular fishing on paramagnetic
      particles: experimental simulation and SPR validation.
AB  - We describe an experimental approach for direct molecular fishing of prey protein
      on the surface of two types of paramagnetic particles (PMP) having different size
      and composition. Human microsomal cytochrome b(5) (b(5)) and its known partner
      human cytochrome P450 3A5 (CYP3A5) were used as bait and prey proteins,
      respectively. For assessing the level of unspecific binding of background
      proteins, alpha-fetoprotein (aFP) was used. SPR measurements were applied for
      quantitative analysis of trapped proteins (CYP3A5 and aFP) after fishing on PMP.
      It was shown that the described approach of molecular fishing on micro-PMP
      provides enough prey proteins for LC-MS/MS identification and SPR validation, so
      this approach can be used for discovery of new protein-protein interactions in
      the framework of Human Proteome Project.

PMID- 23001862
TI  - Gold nanoprisms as optoacoustic signal nanoamplifiers for in vivo bioimaging of
      gastrointestinal cancers.
AB  - Early detection of cancer greatly increases the chances of a simpler and more
      effective treatment. Traditional imaging techniques are often limited by shallow
      penetration, low sensitivity, low specificity, poor spatial resolution or the use
      of ionizing radiation. Hybrid modalities, like optoacoustic imaging, an emerging
      molecular imaging modality, contribute to improving most of these limitations.
      However, this imaging method is hindered by relatively low signal contrast. Here,
      gold nanoprisms (AuNPrs) are used as signal amplifiers in multispectral
      optoacoustic tomography (MSOT) to visualize gastrointestinal cancer. PEGylated
      AuNPrs are successfully internalized by HT-29 gastrointestinal cancer cells in
      vitro. Moreover, the particles show good biocompatibility and exhibit a surface
      plasmon band centered at 830 nm, a suitable wavelength for optoacoustic imaging
      purposes. These findings extend well to an in vivo setting, in which mice are
      injected with PEGylated AuNPrs in order to visualize tumor angiogenesis in
      gastrointestinal cancer cells. Overall, both our in vitro and in vivo results
      show that PEGylated AuNPrs have the capacity to penetrate tumors and provide a
      high-resolution signal amplifier for optoacoustic imaging. The combination of
      PEGylated AuNPrs and MSOT represents a significant advance for the in vivo
      imaging of cancers.

PMID- 23001863
TI  - The effect of atypical antipsychotic medications in individuals with anorexia
      nervosa: a systematic review and meta-analysis.
AB  - OBJECTIVE: Given that atypical antipsychotic medications have been increasingly
      prescribed for improving weight gain in anorexia nervosa (AN), we conducted a
      systematic review and meta-analyses to estimate the influence of atypical
      antipsychotics on BMI, eating disorder, and psychiatric symptoms in individuals
      with AN. METHOD: Independent reviewers selected studies and extracted study
      characteristics, methodologic quality, and outcomes for the intention-to-treat
      group from randomized clinical trials comparing the effect of atypical
      antipsychotic use to placebo or an active control treatment on BMI. RESULTS:
      Compared with placebo, atypical antipsychotics were associated with a
      nonsignificant increase in BMI (weighted mean difference, WMD = 0.18, 95% CI: 
      0.36, 0.72; I(2) = 26%) and a nonsignificant effect on the drive for thinness and
      body dissatisfaction. Compared with placebo or active control, these medications
      led to an increase in anxiety and overall eating disorder symptoms. However,
      there was a significant reduction over placebo or active control on level of
      depression.

PMID- 23001864
TI  - Assessment of cortical bone with clinical and ultrashort echo time sequences.
AB  - We describe the use of ultrashort echo time (UTE) sequences and fast spin echo
      sequences to assess cortical bone using a clinical 3T scanner. Regular two- and
      three-dimensional UTE sequences were used to image both bound and free water in
      cortical bone. Adiabatic inversion recovery prepared UTE sequences were used to
      image water bound to the organic matrix. Two-dimensional fast spin echo sequences
      were used to image free water. Regular UTE sequences were used together with
      bicomponent analysis to measure T*2s and relative fractions of bound and free
      water components in cortical bone. Inversion recovery prepared UTE sequences were
      used to measure the T*2 of bound water. Saturation recovery UTE sequences were
      used to measure the T1 of bone water. Eight cadaveric human cortical bone samples
      and a lower leg specimen were studied. Preliminary results show two distinct
      components in UTE detected signal decay, a single component in inversion recovery
      prepared UTE detected signal decay, and a single component in saturation recovery
      UTE detected signal recovery. Regular UTE sequences appear to depict both bound
      and free water in cortical bone. Inversion recovery prepared UTE sequences appear
      to depict water bound to the organic matrix. Two-dimensional fast spin echo
      sequences appear to depict bone structure corresponding to free water in large
      pores.

PMID- 23001865
TI  - Evaluating WHO Healthy Cities in Europe: issues and perspectives.
AB  - In this introductory article, we situate the findings of the Phase IV evaluation
      effort of the WHO European Healthy Cities Network in its historic evolutionary
      development. We review each of the contributions to this supplement in terms of
      the theoretical and methodological frameworks applied. Although the findings of
      each are both relevant and generated with a scholarly rigor that is appropriate
      to the context in which the evaluation took place, we find that particularly
      these contextual factors have not contributed to optimum quality of research. Any
      drawbacks in individual contributions cannot be attributed to their analysts and
      authors but relate to the complicated and evolving nature of the project. These
      factors are also reviewed. 

PMID- 23001866
TI  - Label-free microscale thermophoresis discriminates sites and affinity of protein
      ligand binding.
AB  - Look, no label! Microscale thermophoresis makes use of the intrinsic fluorescence
      of proteins to quantify the binding affinities of ligands and discriminate
      between binding sites. This method is suitable for studying binding interactions
      of very small amounts of protein in solution. The binding of ligands to iGluR
      membrane receptors, small-molecule inhibitorss to kinase p38, aptamers to
      thrombin, and Ca(2+)  ions to synaptotagmin was quantified.

PMID- 23001868
TI  - Serum protein N-glycan alterations of diethylnitrosamine-induced hepatocellular
      carcinoma mice and their evolution after inhibition of the placental growth
      factor.
AB  - Placental growth factor (PlGF) inhibition produced promising results in reducing
      tumor burden in a diethylnitrosamine (DEN)-induced mouse model for hepatocellular
      carcinoma (HCC). The aim of this study was to non-invasively assess the improved
      histology by performing a serum glycomic analysis. To elucidate the molecular
      mechanism underlying the observed glycomic effects, we investigated the
      transcription and expression of E26 transformation-specific sequence 1 (Ets-1), a
      transcription factor essential for the glycomic and angiogenic changes in
      malignant transformation, including its different phosphorylated forms that
      result from activation of the MAP kinase and a Ca(2+)-dependent pathway. In
      addition, three Ets-1-dependent glycosyltransferase genes, Mgat4a, Mgat4b, and
      Mgat5, were also evaluated. HCC was induced in mice by weekly injections with DEN
      for 16, 20, 25, and 30 w. In the treatment study, mice were injected with DEN for
      25 w and subsequently treated with PlGF antibodies (5D11D4) for 5 w. Finally,
      PlGF-/- mice were injected with DEN for 20, 25, and 30 w. Serum N-glycans were
      analyzed with DNA sequencer-assisted fluorophore-assisted capillary
      electrophoresis and compared with histology. Maximum altered N-glycan phenotype
      was reached after 20 w of DEN-injections, i.e., when the first neoplastic lesions
      started to appear. 5D11D4-treatment improved the glycomic phenotype in that 7 of
      the 11 altered glycans tended to normalize. The PlGF-/- mice also showed a
      normalization trend, although not to the same extent of the treatment group.
      Number of Ets1, Mgat4a, Mgat4b, and Mgat5 transcripts increased considerably in
      DEN-injected mice, however, a non-significant decrease was observed after 5D11D4
      treatment. On the protein level, 5D11D4-treatment had a prominent effect on the
      MAP kinase pathway with a significant p38 activation, yet independent of Ets-1
      function.

PMID- 23001867
TI  - Construction and characterization of virus-like particles: a review.
AB  - Over the last three decades, virus-like particles (VLPs) have evolved to become a
      widely accepted technology, especially in the field of vaccinology. In fact, some
      VLP-based vaccines are currently used as commercial medical products, and other
      VLP-based products are at different stages of clinical study. Several remarkable
      advantages have been achieved in the development of VLPs as gene therapy tools
      and new nanomaterials. The analysis of published data reveals that at least 110
      VLPs have been constructed from viruses belonging to 35 different families. This
      review therefore discusses the main principles in the cloning of viral structural
      genes, the relevant host systems and the purification procedures that have been
      developed. In addition, the methods that are used to characterize the structural
      integrity, stability, and components, including the encapsidated nucleic acids,
      of newly synthesized VLPs are analyzed. Moreover, some of the modifications that
      are required to construct VLP-based carriers of viral origin with defined
      properties are discussed, and examples are provided.

PMID- 23001869
TI  - The JNK/c-Jun signaling axis contributes to the TDP-43-induced cell death.
AB  - Dysregulation of transactive response DNA-binding protein-43 (TDP-43) is closely
      linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).
      The contribution of the upregulation of TDP-43 expression to the pathogenesis has
      been strongly suggested by the observation that the level of TDP-43 expression is
      increased in both ALS and FTLD-U patients. We previously found that the low-grade
      (twice to five times more than the endogenous level) overexpression of TDP-43
      induces neuronal cell death through the upregulation of Bim and CHOP expression
      and the downregulation of Bcl-xL expression. In this study, we further show that
      the low-grade overexpression of TDP-43 increases the level of phosphorylated c
      Jun N-terminal kinase (JNK) and the co-incubation with a JNK inhibitor, the
      expression of a dominant-negative JNK, or the expression of a dominant-negative c
      Jun inhibited the TDP-43-induced death in NSC34 motor neuronal cells. These data
      together suggest that the JNK/c-Jun signaling axis contributes to the TDP-43
      induced cell death.

PMID- 23001870
TI  - PPARgamma antagonist GW9662 induces functional estrogen receptor in mouse mammary
      organ culture: potential translational significance.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      plays a central role in regulating metabolism, including interaction with the
      estrogen receptor-alpha (ERalpha). Significantly, PPARgamma activity can be
      modulated by small molecules to control cancer both in vitro and in vivo (Yin et
      al., Cancer Res 69:687-694, 2009). Here, we evaluated the effects of the
      PPARgamma agonist GW7845 and the PPARgamma antagonist GW9662 on DMBA-induced
      mammary alveolar lesions (MAL) in a mouse mammary organ culture. The results were
      as follows: (a) the incidence of MAL development was significantly inhibited by
      GW 7845 and GW 9662; (b) GW9662 but not GW7845, in the presence of estradiol,
      induced ER and PR expression in mammary glands and functional ERalpha in MAL; (c)
      while GW9662 inhibited expression of adipsin and ap2, GW 7845 enhanced expression
      of these PPARgamma-response genes; and (d) Tamoxifen caused significant
      inhibition of GW9662 treated MAL, suggesting that GW9662 sensitizes MAL to
      antiestrogen treatment, presumably through rendering functional ERalpha and
      induction of PR. The induction of ERalpha by GW9662, including newer analogs, may
      permit use of anti-ER strategies to inhibit breast cancer in ER- patients.

PMID- 23001871
TI  - Association of the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G
      polymorphisms with gastric cancer risk and survival in the Korean population.
AB  - We investigated whether four common microRNA polymorphisms (miR-146aC>G
      [rs2910164], miR-149T>C [rs2292832], miR-196a2T>C [rs11614913], and miR-499A>G
      [rs3746444]) are associated with the susceptibility and prognosis of gastric
      cancer in the Korean population. The four microRNA single-nucleotide
      polymorphisms (SNPs) were identified in a case-control study (461 patients; 447
      controls) by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) analysis in the Korean population. When patients were stratified into
      diffuse and intestinal-type gastric cancer groups, subjects with the miR-499AG
      and AG + GG genotypes had reduced adjusted odds ratios (AORs) for diffuse-type
      gastric cancer (AOR = 0.54 with 95% confidence interval [CI] = 0.31-0.97; AOR =
      0.57 with 95% CI = 0.33-0.97). In the stratified analyses for gastric cancer
      risk, the miR-146aGG and CG + GG genotypes were associated with increased risk of
      gastric cancers among the non-smokers, whereas the miR-149TC and TC + CC
      genotypes showed lower risk of gastric cancer in males. The miR-196a2CC genotype
      was associated with elevated gastric cancer risk among females. For gastric
      cancer prognosis, intestinal-type gastric cancer patients with miR-146aCG + GG
      genotypes had significantly higher survival rates (log-rank P = 0.030) than
      patients with the CC genotype, and patients with the miR-499AA genotype had
      significantly increased survival rates compared to patients with the AG + GG
      genotypes (log-rank P = 0.013). When miR-146aCG + GG and miR-499AA genotypes were
      combined, the survival rate of intestinal-type gastric cancer patients was
      elevated (log-rank P < 0.001). No association was found between gastric or
      diffuse-type cancer prognosis and other miRNAs. Our data demonstrate that
      specific miRNA SNPs are associated with gastric cancer susceptibility (miR
      499A>G) and prognosis (miR-146aC>G and miR-499A>G) in the Korean population
      depending on gastric cancer type.

PMID- 23001873
TI  - Immunohistochemical and fluorescence in situ hybridization studies on noninvasive
      and invasive extramammary Paget's disease.
AB  - To determine useful immunohistochemical markers for tumor cells in extramammary
      Paget's disease (EMPD), immunohistochemical (IHC) examinations in 17 patients
      with EMPD, including 4 patients with dermal invasion, were performed. Among the
      antibodies examined, cytokeratin 7 (CK7) and CK19 were strongly positive for both
      intraepidermal and dermally invasive tumor cells in all patients. CAM5.2 and
      mucin 1 (MUC1) were also good markers. Although IHC examination revealed positive
      for HER-2 in 4 EMPD patients with dermal invasion, 4 out of 13 noninvasive
      patients were IHC negative. Fluorescence in situ hybridization (FISH) study
      revealed negative results for HER-2 gene amplification in 8 IHC positive
      patients, including each 4 patients of both noninvasive and dermal invasive
      cases. Our results show that besides CK7, CK19 is another favorable marker of
      tumor cells of EMPD. Four patients with dermal invasion were strongly positive
      for HER-2, although negative results were obtained in the FISH study. Further
      investigations are required to confirm the results of the FISH study.

PMID- 23001872
TI  - Estrogen modulation of nitric oxide signaling in the airway.

PMID- 23001875
TI  - Striking a balance: autophagy, apoptosis, and necrosis in a normal and failing
      heart.
AB  - Despite the progress that has been made over the past two decades in
      cardiovascular research, heart failure remains a major cause of morbidity and
      mortality worldwide. Insight into the cellular and molecular mechanisms that
      underlie the heart failure in individuals with ischemic heart disease have
      identified defects in cellular processes that govern autophagy, apoptosis and
      necrosis as a prevailing underlying cause. Indeed, programmed cell death of
      cardiac cells by apoptosis or necrosis is believed to involve the intrinsic
      mitochondrial pathway and/or extrinsic death receptor pathway by certain Bcl-2
      family members as well as components of the TNFalpha signaling pathway. In this
      review, we discuss recent advances in the molecular signaling factors that govern
      cardiac cell fate under normal and disease conditions.

PMID- 23001876
TI  - Pubic arch angle in prolonged second stage of labor: clinical significance.
AB  - OBJECTIVE: To evaluate the clinical significance of the pubic arch angle (PAA)
      measured by transperineal ultrasound during prolonged second stage of labor.
      METHODS: We evaluated prospectively 62 women >= 37 weeks of gestation with
      failure to progress in the second stage of labor. Transperineal ultrasound
      (transverse plane) was used to measure the pubic arch angle. Correlations with
      fetomaternal characteristics, mode of delivery and perinatal outcome were
      evaluated. RESULTS: The mean PAA was 101.1 degrees  (+/- 13.1 degrees ; range, 80
      degrees -135 degrees ). We found a negative correlation with maternal age.
      Patients with an occipitotransverse fetal position had a significantly smaller
      angle compared with those with occipitoanterior positions (94.3 degrees  +/- 5.5
      degrees  vs. 103.2 degrees  +/- 14.8 degrees , P < 0.05), as did those with
      operative deliveries compared with those with spontaneous vaginal delivery (97.1
      degrees  +/- 11.5 degrees  vs. 110.1 degrees  +/- 14.0 degrees , P < 0.05). The
      prediction of operative delivery in prolonged second stage of labor by receiver
      operating characteristics curve using PAA alone yielded an area under the curve
      of 0.75. The predicted probability for operative delivery increased as PAA
      decreased, with an odds ratio of 0.933 for each decrease in angle of 1 degrees .
      CONCLUSION: Our study suggests a correlation between the PAA and mode of delivery
      in prolonged second stage of labor. This may be used as an adjunctive parameter
      when considering delivery mode.

PMID- 23001878
TI  - A spectroscopic and computational study of propofol dimers and their hydrated
      clusters.
AB  - Propofol (2,6-diisopropylphenol, PPF) homodimers and their complexes with one
      water molecule are analyzed by means of mass-resolved excitation spectroscopy.
      Using two-color resonance-enhanced multiphoton ionization (REMPI) the S(1)
      electronic spectra of these systems are obtained, avoiding fragmentation. Due to
      the large size of these species, the spectra present a large abundance of lines.
      Using UV/UV hole-burning spectroscopy, two isomers of PPF(2) are found and the
      existence of at least three isomers for propofol(2)(H(2)O)(1) (PPF(2)W(1)) is
      demonstrated. Comparison with the structures calculated at the M06-2X/6
      311++G(d,p) and M06-2X/6-31+G(d) levels of theory shows that the main driving
      forces in PPF(2) are several C-H...pi interactions accompanied by dipole-dipole
      interaction between the OH moieties. On the other hand, there is evidence for the
      formation of cyclic hydrogen-bond structures in the heterotrimers. A comparison
      of the results obtained herein with those of similar systems from previously
      published studies follows.

PMID- 23001877
TI  - Interleukin-13-producing CD8+ T cells mediate dermal fibrosis in patients with
      systemic sclerosis.
AB  - OBJECTIVE: Fibrosis is a major contributor to morbidity and mortality in systemic
      sclerosis (SSc). T cells are the predominant inflammatory infiltrate in affected
      tissue and are thought to produce cytokines that drive the synthesis of
      extracellular matrix (ECM) proteins by fibroblasts, resulting in excessive
      fibrosis. We have previously shown that aberrant interleukin-13 (IL-13)
      production by peripheral blood effector CD8+ T cells from SSc patients correlates
      with the extent of skin fibrosis. The present study was undertaken to investigate
      the role of IL-13 production by CD8+ T cells in dermal fibrosis, an early and
      specific manifestation of SSc. METHODS: ECM protein production by normal dermal
      fibroblasts cocultured with SSc CD8+ T cell supernatants was determined by
      quantitative polymerase chain reaction and Western blotting. Skin-homing receptor
      expression and IL-13 production by CD8+ T cells in the peripheral blood of SSc
      patients were measured by flow cytometry. IL-13+ and CD8+ cells in sclerotic skin
      were identified by immunohistochemistry. RESULTS: IL-13-producing circulating
      CD8+ T cells from patients with SSc expressed skin-homing receptors and induced a
      profibrotic phenotype in normal dermal fibroblasts, which was inhibited by an
      anti-IL-13 antibody. High numbers of CD8+ T cells and IL-13+ cells were found in
      the skin lesions of SSc patients, particularly during the early inflammatory
      phase of the disease. CONCLUSION: These findings show that IL-13-producing CD8+ T
      cells are directly involved in modulating dermal fibrosis in SSc. The
      demonstration that CD8+ T cells homing to the skin early in the course of SSc are
      associated with accumulation of IL-13 is an important mechanistic contribution to
      the understanding of the pathogenesis of dermal fibrosis in SSc and may represent
      a potential target for therapeutic intervention.

PMID- 23001879
TI  - Neuroimaging predictors of stroke outcome: implications for neurorehabilitation.
AB  - Advances in neuroimaging have greatly improved our understanding of stroke not
      only in the acute, but also in the subacute and chronic stages of recovery. More
      recently developed magnetic resonance techniques such as diffusion and perfusion
      weighted imaging, as well as more traditional magnetic resonance and computed
      tomography studies allow clinicians to more accurately diagnosis stroke subtypes,
      optimize treatment, and predict prognosis. Although not widely utilized for
      clinical use, functional neuroimaging techniques have also been shown to be
      useful in terms of predicting prognosis and advancing our understanding of
      reorganization and recovery following stroke. Thus, neuroimaging in stroke may
      also be utilized to monitor response to both medical treatment as well as
      physical rehabilitation. The following is a review of current research relevant
      to the field of neuroimaging of stroke. We begin with a discussion of structural
      imaging techniques with the goal of familiarizing the reader with recent
      developments in this area. Next, the discussion moves to functional imaging, its
      role in advancing our understanding of neuronal reorganization and functional
      recovery following stroke, and its usefulness at predicting recovery. Finally, a
      brief discussion regarding the future of neuroimaging and its implications for
      stroke and stroke recovery is presented.

PMID- 23001880
TI  - Identification and characterization of histatin 1 salivary complexes by using
      mass spectrometry.
AB  - With recent progress in the analysis of the salivary proteome, the number of
      salivary proteins identified has increased dramatically. However, the
      physiological functions of many of the newly discovered proteins remain unclear.
      Closely related to the study of a protein's function is the identification of its
      interaction partners. We investigated interactions among and functions of
      histatin 1 and the other proteins that are present in saliva by using high
      throughput mass spectrometric techniques. This led to the identification of 43
      proteins able to interact with histatin 1. In addition, we found that these
      protein-protein interactions protect complex partners from proteolysis and
      modulate their antifungal activity. Our data contribute significantly to
      characterization of the salivary interactome and to understanding the biology of
      salivary protein complexes.

PMID- 23001881
TI  - Improved long-term outcomes of patients with chronic myelogenous leukemia and a
      rising prevalence of disease.

PMID- 23001882
TI  - Coordination polymer coated mesoporous silica nanoparticles for pH-responsive
      drug release.
AB  - Coordination polymer coated mesoporous silica nanoparticles for drug delivery are
      successfully synthesized. The system ensures that drugs are stored in the
      mesopores under a physiological environment. Upon H(+)  stimulus in the endosomal
      and lysosomal compartments, the drugs are released into the intracellular
      organelles of cancer cells, effectively killing the cells.

PMID- 23001885
TI  - Automated online pretreatment and cleanup recycle coupled with high-performance
      liquid chromatography-mass spectrometry for determination of deca-bromodiphenyl
      ether in human serum.
AB  - Automated online SPE-HPLC-MS was established for the determination of deca
      bromodiphenyl ether in human serum. The online SPE with large volume injection
      was utilized to enhance the sensitivity. Online SPE with dilution line greatly
      decreased matrices effect, which enabled serum samples to be injected directly
      into pre-column. Washing line was designed for the system to solve the serious
      residual phenomenon and reduce the risk of sample wastage and contamination.
      Under the optimized conditions, the linear of the method was in the range 0.1-10
      ng/mL with the LOD of 0.026 ng/mL. The recoveries of serum samples spiked with
      deca-bromodiphenyl ether at 0.5 ng/mL was in the range from 83.30 to 102.7% with
      RSD in interday less than 8.67%. The satisfactory results demonstrated that the
      method of online sample pretreatment and cleanup recycle were reliable for human
      serum analysis.

PMID- 23001883
TI  - GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration.
AB  - GPR56, a member of the adhesion G protein-coupled receptor (GPCR) family, is
      integral to the development of the cortex, as mutations in GPR56 cause bilateral
      frontoparietal polymicrogyria (BFPP). BFPP is a cobblestone-like cortical
      malformation, characterized by overmigrating neurons and the formation of
      neuronal ectopias on the surface of the brain. Since its original cloning a
      decade ago, GPR56 has emerged from an orphaned and uncharacterized protein to an
      increasingly well-understood receptor, both in terms of its signaling and
      function. Collagen III is the ligand of GPR56 in the developing brain. Upon
      binding to collagen III, GPR56 activates RhoA via coupling to Galpha(12/13). This
      pathway appears to be particularly critical in the preplate neurons, which are
      the earliest born neurons in the cortex, as the expression pattern of GPR56 in
      these neurons mimics the anterior to posterior gradient of malformation
      associated with loss of GPR56 in both humans and mice. Further characterizing the
      role of GPR56 in the preplate will shed light on the mechanism of cortical
      development and patterning.

PMID- 23001884
TI  - Misfolded proteins recognition strategies of E3 ubiquitin ligases and
      neurodegenerative diseases.
AB  - Impairment in the clearance of misfolded proteins by functional proteins leads to
      various late-onset neurodegenerative diseases. Cell applies a strict quality
      control mechanism against malfunctioned proteins which may generate cellular
      proteoxicity. Under proteotoxic insults, cells immediately adopt two major
      approaches to either refold the misfolded proteinaceous species or degrade the
      unmanageable candidates. However, the main cellular proteostasis quality control
      mechanism is not clear. It is therefore important to understand the events and
      cellular pathways, which are implicated in the clearance of recalcitrant
      proteins. Ubiquitin proteasome system manages intracellular protein degradation.
      In this process, E3 ubiquitin ligase enzyme provides specificity for recognition
      of client proteins. In this review, we summarize various molecular approaches
      governed by E3 ubiquitin ligases in the degradation of aberrant proteins. A clear
      understanding of E3 ubiquitin ligases can offer a well tractable therapeutic
      approach against neurodegenerative diseases.

PMID- 23001886
TI  - Preparative isolation and purification of harpagoside and angroside C from the
      root of Scrophularia ningpoensis Hemsley by high-speed counter-current
      chromatography.
AB  - In this study, the bioactive component harpagoside and angroside C in the root of
      Scrophularia ningpoensis Hemsley was simultaneously separated by high-speed
      counter-current chromatography (HSCCC). A two-phase solvent system containing
      chloroform/n-butanol/methanol/water (4:1:3:2, v/v/v/v) was selected following
      consideration of the partition coefficient of the target compound. The crude
      extract (200 mg) was loaded onto a 280-mL HSCCC column and yielded 22 mg
      harpagoside and 31 mg angroside C with the purity of higher than 98 and 98.5%,
      respectively. It is feasible to isolate active compounds harpagoside and
      angroside C from S. ningpoensis using HSCCC.

PMID- 23001889
TI  - Development and pilot evaluation of Native CREST-a Cancer Research Experience and
      Student Training program for Navajo undergraduate students.
AB  - The Mayo Clinic Cancer Center and Dine College received funding for a 4-year
      collaborative P20 planning grant from the National Cancer Institute in 2006. The
      goal of the partnership was to increase Navajo undergraduates' interest in and
      commitment to biomedical coursework and careers, especially in cancer research.
      This paper describes the development, pilot testing, and evaluation of Native
      CREST (Cancer Research Experience and Student Training), a 10-week cancer
      research training program providing mentorship in a Mayo Clinic basic science or
      behavioral cancer research lab for Navajo undergraduate students. Seven Native
      American undergraduate students (five females, two males) were enrolled during
      the summers of 2008-2011. Students reported the program influenced their career
      goals and was valuable to their education and development. These efforts may
      increase the number of Native American career scientists developing and
      implementing cancer research, which will ultimately benefit the health of Native
      American people.

PMID- 23001890
TI  - Towards a new procreation ethic: the exemplary instance of cleft lip and palate.
AB  - The improvement of ultrasound scan techniques is enabling ever earlier prenatal
      diagnosis of developmental anomalies. In France, apart from cases where the
      mother's life is endangered, the detection of "particularly serious" conditions,
      and conditions that are "incurable at the time of diagnosis" are the only
      instances in which a therapeutic abortion can be performed, this applying up to
      the 9th month of pregnancy. Thus numerous conditions, despite the fact that they
      cause distress or pain or are socially disabling, do not qualify for therapeutic
      abortion, despite sometimes pressing demands from parents aware of the
      difficulties in store for their child and themselves, in a society that is not
      very favourable towards the integration and self-fulfilment of people with a
      disability. Cleft lip and palate (CLP), although it can be completely treated, is
      one of the conditions that considerably complicates the lives of child and
      parents. Nevertheless, the recent scope for making very early diagnosis of CLP,
      before the deadline for legal voluntary abortion, has not led to any wave of
      abortions. CLP in France has the benefit of a exceptional care plan, targeting
      both the health and the integration of the individuals affected. This article
      sets out, via the emblematic instance of CLP, to show how present fears of an
      emerging "domestic" or liberal eugenic trend could become redundant if disability
      is addressed politically and medically, so that individuals with a disability
      have the same social rights as any other citizen.

PMID- 23001891
TI  - Mesoporous metal and metal alloy particles synthesized by aerosol-assisted
      confined growth of nanocrystals.
AB  - From droplets to "spheres": A platform technology enables the rapid and
      continuous synthesis of mesoporous metal and metal alloy particles (see picture).
      The confined growth of nanocrystals in aerosol droplets leads to the formation of
      these particles with defined composition.

PMID- 23001892
TI  - Prediction of pouch of Douglas obliteration in women with suspected endometriosis
      using a new real-time dynamic transvaginal ultrasound technique: the sliding
      sign.
AB  - OBJECTIVE: To evaluate preoperative real-time dynamic transvaginal sonography
      (TVS) in the prediction of pouch of Douglas (POD) obliteration in women
      undergoing laparoscopy for suspected endometriosis. METHODS: This was a
      multicenter prospective observational study undertaken from January 2009 to
      November 2011. All women with symptoms suggestive of endometriosis who were
      scheduled for laparoscopy underwent detailed preoperative TVS, in particular to
      ascertain whether the POD was obliterated. POD obliteration was assessed using a
      real-time TVS technique called the 'sliding sign'. Preoperative TVS sliding sign
      findings were then compared to gold standard laparoscopic POD findings. RESULTS:
      One hundred consecutive women with preoperative TVS and laparoscopic outcomes
      were included in the final analysis. Mean age was 32.8 years and mean age at
      diagnosis of endometriosis was 27.4 years. At laparoscopy, 84/100 (84%) were
      found to have some form of endometriosis (73% peritoneal endometriosis, 35%
      ovarian endometrioma(s), 33% deep infiltrating endometriosis). At laparoscopy,
      30/100 (30%) had an obliterated POD and 19/30 (63.3%) of these women also had
      evidence of bowel endometriosis. The sonographic sliding sign technique had an
      accuracy of 93.0%, sensitivity of 83.3%, specificity of 97.1%, positive
      predictive value of 92.6%, negative predictive value of 93.2%, positive
      likelihood ratio of 29.2 and negative likelihood ratio of 0.17 in the prediction
      of POD obliteration (P = 1.8E-16). CONCLUSIONS: Preoperative real-time dynamic
      TVS evaluation using the sliding sign seems to establish with a high degree of
      certainty whether the POD is obliterated. Given the increased risk of deep
      infiltrating endometriosis in women with POD obliteration, the TVS sliding sign
      technique may also be useful in the identification of women who may be at a
      higher risk for bowel endometriosis.

PMID- 23001893
TI  - Joint modeling quality of life and survival using a terminal decline model in
      palliative care studies.
AB  - Palliative medicine is a relatively new specialty that focuses on preventing and
      relieving the suffering of patients facing life-threatening illness. For cancer
      patients, clinical trials have been carried out to compare concurrent palliative
      care with usual cancer care in terms of longitudinal measurements of quality of
      life (QOL) until death, and overall survival is usually treated as a secondary
      endpoint. It is known that QOL of patients with advanced cancer decreases as
      death approaches; however, in previous clinical trials, this association has
      generally not been taken into account when inferences about the effect of an
      intervention on QOL or survival have been made. We developed a new joint modeling
      approach, a terminal decline model, to study the trajectory of repeated
      measurements and survival in a recently completed palliative care study. This
      approach takes the association of survival and QOL into account by modeling QOL
      retrospectively from death. For those patients whose death times are censored,
      marginal likelihood is used to incorporate them into the analysis. Our approach
      has two submodels: a piecewise linear random intercept model with serial
      correlation and measurement error for the retrospective trajectory of QOL and a
      piecewise exponential model for the survival distribution. Maximum likelihood
      estimators of the parameters are obtained by maximizing the closed-form
      expression of log-likelihood function. An explicit expression of quality-adjusted
      life years can also be derived from our approach. We present a detailed data
      analysis of our previously reported palliative care randomized clinical trial.

PMID- 23001894
TI  - Localization of cytokinesis factors to the future cell division site by
      microtubule-dependent transport.
AB  - The mechanism by which spindle microtubules (MTs) determine the site of cell
      division in animal cells is still highly controversial. Putative cytokinesis
      "signals" have been proposed to be positioned by spindle MTs at equatorial
      cortical regions to increase cortical contractility and/or at polar regions to
      decrease contractility [Rappaport, 1986; von Dassow, 2009]. Given the relative
      paucity of MTs at the future division site, it has not been clear how MTs
      localize cytokinesis factors there. Here, we test cytokinesis models using
      computational and experimental approaches. We present a simple lattice-based
      model in which signal-kinesin complexes move by transient plus-end directed
      movements on MTs interspersed with occasions of uniform diffusion in the
      cytoplasm. In simulations, complexes distribute themselves initially at the
      spindle midzone and then move on astral MTs to accumulate with time at the
      equatorial cortex. Simulations accurately predict cleavage patterns of cells with
      different geometries and MT arrangements and elucidate several experimental
      observations that have defied easy explanation by previous models. We verify this
      model with experiments on indented sea urchin zygotes showing that cells often
      divide perpendicular to the spindle at sites distinct from the indentations.
      These studies support an equatorial stimulation model and provide a simple
      mechanism explaining how cytokinesis factors localize to the future division
      site.

PMID- 23001895
TI  - The role of diet in osteoporosis prevention and management.
AB  - Diet, a modifiable osteoporosis risk factor, plays an important role in the
      acquisition and maintenance of bone mass. The influence of diet on bone begins in
      childhood; even maternal diet can influence bone mass in the offspring. A good
      general nutritional status and adequate dietary protein, calcium, vitamin D,
      fruits, and vegetables have a positive influence on bone health, while a high
      caloric diet and heavy alcohol consumption have been associated with lower bone
      mass and higher rates of fracture. The evidence for a role of other minerals and
      vitamins in skeletal health is not as strong, but recent evidence suggests that
      vitamins C and K might also have an effect on bone.

PMID- 23001896
TI  - Cardiac allograft function during the first year after transplantation in
      rejection-free children and young adults.
AB  - BACKGROUND: Allograft dysfunction is a common finding early after heart
      transplant (HT). We sought to assess the recovery of left (LV) and right
      ventricular (RV) function during the first year after HT in children and young
      adults using pulsed-wave tissue Doppler imaging. METHODS AND RESULTS: We analyzed
      serially performed echocardiography in 44 pediatric HT recipients (median age:
      7.3 years at HT) who remained rejection-free during the first year post
      transplant. Age-based normative values for systolic (S'), early-diastolic (E'),
      and late-diastolic (A') velocities obtained using pulsed-wave tissue Doppler
      imaging in 380 healthy children were used to transform patient data into z
      scores. Pulsed-wave tissue Doppler imaging studies <=10 days post-HT demonstrated
      biventricular systolic and diastolic dysfunction with most prominent impairment
      in RV systolic function (S' z score -2.7+/-0.8), RV early-diastolic filling (E' z
      score -2.3+/-1.1), and LV early-diastolic filling (E' z score -2.3+/-1.1). LV
      systolic function (S' z score) and late-diastolic filling (A' z score) improved
      to normal in 11 to 30 days, LV early-diastolic filling (E' z score) in 4 to 6
      months, and RV early-diastolic filling in 6 to 9 months (P<0.001 for all on
      longitudinal analysis). However, RV systolic function (RV S' z score -1.2+/-1.1)
      remained impaired 1-year post-transplant. Analysis of serial cardiac
      catheterization studies showed that RV and LV filling pressures were elevated
      early post-HT and declined gradually during the first year post-transplant.
      CONCLUSIONS: Pediatric HT recipients have biventricular dysfunction using pulsed
      wave tissue Doppler imaging early after HT with most significant impairment in RV
      systolic function and RV and LV early-diastolic filling. Although other aspects
      of LV and RV function normalize in 6 to 9 months, RV systolic function remains
      abnormal 1 year-post-transplant.

PMID- 23001897
TI  - Analysis of procedural effects of percutaneous edge-to-edge mitral valve repair
      by 2D and 3D echocardiography.
AB  - BACKGROUND: Analysis of procedural effects in patients undergoing percutaneous
      mitral valve repair (PMVR) using the edge-to-edge technique is complex, and
      common methods to define mitral regurgitation severity based on 2-dimensional
      (2D) echocardiography are not validated for postprocedural double-orifice mitral
      valve. This study used 3D transesophageal echocardiography (TEE) to determine the
      functional and morphological effects of PMVR. METHODS AND RESULTS: In 39 high
      risk surgical patients with moderate to severe functional mitral valve
      regurgitation, 3D TEE with and without color Doppler as well as 2D transthoracic
      and TEE was performed before and after PMVR (MitraClip device). Mitral valve
      regurgitant volume by color Doppler 3D TEE was determined as the product of vena
      contracta areas defined by direct planimetry and velocity time integral using
      continuous-wave Doppler. Regurgitant volume was reduced from 84.1+/-38.3 mL
      preintervention to 35.6+/-25.6 mL postintervention. Patients in whom vena
      contracta area could be reduced >50% had a smaller preprocedural mitral annulus
      area compared with patients with <=50% reduction (11.9+/-3.9 versus 16.1+/-8.5
      cm(2), respectively; P=0.036) and tended to have a smaller mitral annulus
      circumference (13.0+/-2.0 versus 14.8+/-4.1 cm, respectively; P=0.112). At 6
      months follow-up, left atrial and left ventricular end-diastolic volumes were
      significantly more reduced in patients in whom regurgitant vena contracta area
      was reduced by >50% compared with those with less reduction (-11.4+/-5.2 versus 
      4.8+/-7.7%; P=0.005, and -11.0+/-7.2 versus -4.5+/-9.3%; P=0.028). The maximum
      diastolic mitral valve area decreased from 6.0+/-2.0 to 2.9+/-0.9 cm(2)
      (P<0.0001). CONCLUSIONS: Three dimensional TEE demonstrates significant reduction
      of regurgitant volume after PMVR. The unique visualization of the mitral valve by
      3D TEE allows improved understanding of the morphological and functional changes
      induced by PMVR.

PMID- 23001898
TI  - Investigating high-concentration monoclonal antibody powder suspension in
      nonaqueous suspension vehicles for subcutaneous injection.
AB  - Developing high-concentration monoclonal antibody (mAb) liquid formulations for
      subcutaneous (s.c.) administration is challenging because increased viscosity
      makes injection difficult. To overcome this obstacle, we investigated a
      nonaqueous powder suspension approach. Three IgG1 mAbs were spray dried and
      suspended at different concentrations in Miglyol(r) 840, benzyl benzoate, or
      ethyl lactate. Suspensions were characterized for viscosity, particle size, and
      syringeability; physical stability was visually inspected. Suspensions generally
      outperformed liquid solutions for injectability despite higher viscosity at the
      same mAb concentrations. Powder formulations and properties had little effect on
      viscosity or injectability. Ethyl lactate suspensions had lowest viscosity (<20
      cP) and lowest syringe injection glide force (<15 N) at mAb concentrations as
      high as 333 mg/mL (500 mg powder/mL). Inverse gas chromatography analysis
      indicated that the vehicle was the most important factor impacting suspension
      performance. Ethyl lactate rendered greater heat of sorption (suggesting strong
      particle-suspension vehicle interaction may reduce particle-particle self
      association, leading to low suspension viscosity and glide force) but lacked the
      physical suspension stability exhibited by the other vehicles. Specific mixtures
      of ethyl lactate and Miglyol(r) 840 improved overall performance in high mAb
      concentration suspensions. This study demonstrated the viability of high mAb
      concentration (>300 mg/mL) in suspension formulations for s.c. administration.

PMID- 23001899
TI  - Continuing professional development: issues raised by nurses and allied health
      professionals working in musculoskeletal settings.
AB  - BACKGROUND: Nurses and allied health professionals (AHPs) are required to
      evidence their engagement in continuing professional development (CPD) in order
      to retain their professional registration. Many challenges to CPD are reported,
      but little literature has explored pertinent CPD issues for clinicians with
      specialist roles or working in specialist services. No literature to date has
      explored the perceptions of CPD held by patients who receive these specialist
      services. METHODS: Three focus groups and two conference calls were conducted
      with nurses, physiotherapists, podiatrists and occupational therapists who work
      in musculoskeletal (MSK) services; managers of these services; and people who use
      MSK services. These focus groups aimed: to explore the CPD needs and issues for
      this group of clinicians; to explore the perceptions of CPD held by people who
      have MSK conditions; and to compare the above with current literature to discern
      any factors specific to MSK settings. The focus groups and conference calls were
      audio-recorded. The recordings were coded by the researchers using a priori and
      inductive coding. RESULTS: The main issues discussed were: funding and time for
      CPD, providing examples of ways to provide CPD in spite of the challenges faced;
      that CPD needs changed with level of experience; initiatives by clinical
      specialists to reduce professional isolation; and future trends in CPD, including
      concerns about succession planning. The views of people with MSK conditions
      demonstrated an emphasis on communication skills that was seldom raised by
      managers and clinicians. CONCLUSIONS: Sufficient time, funding and provision of
      study leave were key to facilitating CPD activity for nurses and AHPs working in
      MSK services. People with MSK conditions particularly valued health professionals
      who combined good listening and communication skills with an attempt to
      understand what it was like to live with their condition.

PMID- 23001900
TI  - The TTTT B lymphocyte stimulator promoter haplotype is associated with good
      response to rituximab therapy in seropositive rheumatoid arthritis resistant to
      tumor necrosis factor blockers.
AB  - OBJECTIVE: To investigate the polymorphisms in the promoter region of the B
      lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in
      rheumatoid arthritis (RA). METHODS: The study was first conducted in 152 Italian
      RA patients and then replicated in an additional 117 RA patients (73 Italian, 44
      British). The European League Against Rheumatism response criteria were used to
      evaluate the response rate at months 4 and 6 after the first cycle of RTX, by
      means of the Disease Activity Score in 28 joints using the erythrocyte
      sedimentation rate; patients were classified according to the best response shown
      between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase
      chain reaction followed by the analysis of the restriction fragments, BLyS
      promoter haplotypes were analyzed using the expectation-maximization algorithm,
      and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds
      ratios (ORs) were calculated with 95% confidence intervals (95% CIs). RESULTS:
      The TTTT BLyS promoter haplotype appeared to be significantly associated with
      response to RTX only in the subset of seropositive patients (those positive for
      rheumatoid factor and/or anti-cyclic citrullinated peptide). The replication
      study confirmed that this association was limited to seropositive RA patients in
      whom treatment with anti-tumor necrosis factor (anti-TNF) agents had previously
      failed. In the whole series of seropositive patients in whom anti-TNF agents had
      previously failed, patients carrying the TTTT BLyS promoter haplotype were more
      prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20
      of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus
      nonresponders, OR 14.4 [95% CI 1.77-117.39], P=0.0028). Furthermore, multivariate
      analysis selected the TTTT BLyS promoter haplotype as an independent marker of
      good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI
      1.7-152.5], P=0.01; for good responders versus moderate responders and
      nonresponders combined, OR 3.1 [95% CI 1.2-7.8], P=0.02). The relationship
      between BLyS polymorphisms and BLyS serum levels remained unclear. CONCLUSION:
      BLyS promoter genotyping may be suitable for identifying seropositive RA patients
      who may have a good response to RTX after anti-TNF agents have failed.

PMID- 23001901
TI  - Fixational saccadic eye movements are altered in anisometropic amblyopia.
AB  - PURPOSE: Amblyopia develops during a critical period in early visual development
      and is characterized by reduced visual sensory functions and structural
      reorganization of the brain. However, little is known about oculomotor functions
      in amblyopes despite the special role of eye movements in visual perception, task
      execution and fixation. Therefore, we studied the relationship of visual deficits
      in anisometropic amblyopia and fixational saccadic eye movements. METHODS: We
      recruited twenty-eight anisometropic amblyopes and twenty-eight age-matched
      control subjects. Using a high-speed eye-tracker, fixational eye-movements of
      both eyes were recorded. A computerized fixational saccadic component analysis of
      eye-movement waveforms was developed to quantify the parameters of fixational
      saccades (FSs) and a simulation model was developed to help explain the FS
      performances. RESULTS: Amblyopic eyes, but not control eyes, showed fewer FSs,
      but these had increased amplitudes, increased peak velocities, and longer inter
      saccadic intervals. The reduced FSs occurred mainly in the 0- to 0.6-degree
      amplitude range, and the probability of FSs with larger amplitudes and longer
      inter-saccadic intervals was significantly higher than in controls. A new
      simulation model analysis suggests that an excitatory-inhibitory activity
      imbalance in superior colliculus may explain these FSs changes. CONCLUSIONS: We
      propose that the abnormal visual processing and circuitry reorganization in
      anisometropic amblyopia has an impact on the fixational saccade generation. We
      see two possible interpretations: (i) altered FSs may be an attempt of the visual
      system to adapt to the deficit, trying to capture more information from a broader
      spatial domain of the visual world so as to enhance the contrast sensitivity to
      low spatial frequencies viewed by the amblyopic eye, or (ii) it may be the cause
      of amblyopia or a contributing factor to the original deficit that aggravates the
      early deprivation.

PMID- 23001902
TI  - High-resolution cerebral blood volume imaging in humans using the blood pool
      contrast agent ferumoxytol.
AB  - Cerebral blood volume maps are usually acquired using dynamic susceptibility
      contrast imaging which inherently limits the spatial resolution and signal to
      noise ratio of the images. In this study, we used ferumoxytol (AMAG
      Pharmaceuticals, Inc., Cambridge, MA), an FDA-approved compound, to obtain high
      resolution cerebral blood volume maps with a steady-state approach in seven
      healthy volunteers. R2* maps (0.8 * 0.8 * 1 mm(3)) were acquired before and after
      injection of ferumoxytol and an intraindividual normalization protocol was used
      to obtain quantitative values. The results show excellent contrast between white
      and gray matter as well as fine highly detailed vascular structures. An average
      blood volume of 4% was found in the brain of all volunteers, consistent with
      prior literature values. A linear relationship was found between ferumoxytol dose
      (mg/kg) and DeltaR2* (1/s) in gray (R(2) = 0.98) and white matter (R(2) = 0.98).
      A quadratic relationship was found in the sagittal sinus (R(2) = 0.98). The
      cerebral blood volume maps compare well with lower resolution dynamic
      susceptibility contrast-MRI and their use should improve the evaluation of small
      and heterogeneous lesions and facilitate intrapatient and interpatient
      comparisons.

PMID- 23001903
TI  - A new strategy for RNA isolation from eukaryotic cells using arginine affinity
      chromatography.
AB  - The relevance of RNA in many biological functions has been recognized, broadening
      the scope of RNA research activities, from basic to applied sciences, also aiming
      the translation to clinical fields. The preparation and purification of RNA is a
      critical step for further application, since the quality of the template is
      crucial to ensure reproducibility and biological relevance. Therefore, the
      establishment of new tools that allows the isolation of pure RNA with high
      quality is of particular importance. New chromatographic strategies for RNA
      purification were considered, exploiting affinity interactions between amino
      acids and nucleic acids. In the present study, a single arginine-affinity
      chromatography step was employed for the purification of RNA from a total
      eukaryotic nucleic acid extract, thus eliminating several steps compared with
      current RNA isolation procedures. The application of this process resulted in a
      high RNA recovery yield of 96 +/- 17% and the quality control analysis revealed a
      high integrity (28S:18S ratio = 1.96) in RNA preparations as well as a good
      purity, demonstrated by the scarce detection of proteins and the reduction on
      genomic DNA contamination to residual concentrations. Furthermore, the
      performance of the new RNA isolation method was tested regarding the
      applicability of the isolated RNA in modern molecular biology techniques. Hence,
      this new affinity approach will simplify the isolation and purification of RNA,
      which can bring great improvements in biomedical investigation.

PMID- 23001904
TI  - Social instability stress in adolescence increases anxiety and reduces social
      interactions in adulthood in male Long-Evans rats.
AB  - We investigated the effects of social instability stress (daily 1-hr isolation,
      change of cage partner, postnatal day 30-45) in adolescence in male rats on open
      field exploration and social behavior in adulthood. Social stressed rats had
      longer latencies to enter the center of an open field and then took longer to
      approach an object placed in the center of the field. When another rat was placed
      in the open field, stressed rats spent less time in social interaction than
      control rats, particularly when paired with another stressed, rather than a
      control, rat. The groups did not differ in social approach tests (when a stimulus
      rat was separated by wire mesh) nor in novel object exploration (when controlling
      for open field anxiety). The results suggest social stress in adolescence
      increases open field anxiety while maintaining exploratory behavior, and alters
      social interactions in adulthood.

PMID- 23001905
TI  - Capacity of endometrial thickness measurement to diagnose endometrial carcinoma
      in asymptomatic postmenopausal women: a systematic review and meta-analysis.
AB  - OBJECTIVES: Measurement of endometrial thickness is an important tool in the
      assessment of women with postmenopausal bleeding, but the role of endometrial
      thickness measurement by ultrasound in asymptomatic women is unclear. The aims of
      this study were to determine: (1) the normal endometrial thickness measured by
      ultrasonography, (2) the prevalence of serious endometrial pathology and (3) the
      sensitivity and specificity of endometrial thickness measurement by transvaginal
      ultrasonography (TVS) for diagnosing premalignant and malignant endometrial
      disease in asymptomatic postmenopausal women. METHODS: A MEDLINE and EMBASE
      search (from inception to January 2011) was performed. Articles reporting on
      endometrial thickness measurement in the diagnosis of endometrial carcinoma and
      atypical hyperplasia in asymptomatic postmenopausal women not using hormone
      replacement therapy (HRT) were selected. Endometrial thickness and the prevalence
      of endometrial (pre)malignancies were recorded. If possible, 2 * 2 tables were
      extracted. RESULTS: Thirty-two studies reporting on 11100 women were included.
      The estimated mean endometrial thickness was 2.9 mm (95% CI, 2.6-3.3 mm). The
      pooled estimated prevalences of endometrial carcinoma and atypical endometrial
      hyperplasia were 0.62% (95% CI, 0.42-0.82%) and 0.59% (95% CI, 0.22-0.96%),
      respectively. Summary estimates for sensitivity and specificity of TVS
      endometrial thickness measurement in the prediction of endometrial carcinoma were
      0.83 (95% CI, 0.19-1.00) and 0.72 (95% CI, 0.23-0.95) for a 5-mm cut-off and 0.33
      (95% CI, 0.04-0.85) and 0.94 (95% CI, 0.92-0.96) for a 6-mm cut-off. CONCLUSIONS:
      The results from this systematic review do not justify the use of endometrial
      thickness as a screening test for endometrial carcinoma and atypical endometrial
      hyperplasia in asymptomatic postmenopausal women not using HRT.

PMID- 23001906
TI  - Survey of the camel urinary proteome by shotgun proteomics using a multiple
      database search strategy.
AB  - We report the first survey of the dromedary camel urinary proteome. Proteins
      retained from ultrafiltration of urine were analysed by GeLC-MS/MS (SDS-PAGE
      followed by LC-MS/MS). In the absence of a complete camel genome sequence, the
      number of protein identifications was maximised by searching three primary
      sequence databases: Swiss-Prot, alpaca and camel EST. This search strategy
      enabled the identification of 1274 peptide sequences, of which 735 were found in
      at least two independent samples. Functional annotations for proteins identified
      from alpaca and camel EST sequences were mapped from basic local alignment search
      tool (protein) searches. These 735 peptides, which included many novel sequences
      found only in the camel EST database, were grouped to 147 protein descriptors.
      Gene ontology term analysis of human proteins with sequence similarity showed
      that camel urine may be particularly enriched in proteins from extracellular
      compartments and vesicles, and with functions that include carbohydrate-binding
      and peptidase inhibitor activities. If their biological functions are conserved
      between species, many of the camel urinary proteins could be involved in various
      stress and immune responses, and some may have antimicrobial activities.

PMID- 23001907
TI  - Serum level of HE4 is closely associated with pulmonary adenocarcinoma
      progression.
AB  - The human epididymis 4 (HE4) protein is expressed in the epididymis and
      respiratory tract. We previously reported that HE4 is also expressed in pulmonary
      adenocarcinoma. The purpose of this study was to investigate serum levels of HE4
      as a biological marker in pulmonary adenocarcinoma. As the trained set, 102
      patients with pulmonary adenocarcinoma who underwent surgery in our institute
      from 2008 to 2011 were evaluated. They were compared with 58 healthy controls and
      16 cases of benign lung disease. In the validation, we used 104 patients with
      pulmonary adenocarcinoma operated on between 2000 and 2007. Postoperative changes
      of serum HE4 levels were investigated in 35 patients. The level of HE4 was
      determined by enzyme immunometric assay and compared with clinicopathological
      factors. In the trained set, HE4 levels in sera in pulmonary adenocarcinoma were
      significantly higher than in healthy controls and benign lung disease. Receiver
      operating characteristic curve showed that HE4 was a good discriminator of
      pulmonary adenocarcinoma (cut-off point, 50.3 pM; area under curve, 0.825; 95 %
      confidence interval, 0.76-0.89, p < 0.001). In the validation set, serum HE4
      levels were significantly correlated with age, nodal status, and carcinoembryonic
      antigen. Furthermore, postoperative increase of HE4 serum levels showed a
      significant correlation with recurrence (p = 0.032). The 5-year overall survival
      rate was 52.6 % in the HE4-positive group compared with 97.1 % in the HE4
      negative group (p = 0.001). These data showed that HE4 expression in sera is
      associated with progression of pulmonary adenocarcinoma and a possible biomarker.

PMID- 23001908
TI  - Heterozygosity for TGF beta1 -509C/T Polymorphism is associated with risk for
      breast cancer in South Indian population.
AB  - Transformation growth factor beta1 is a multipotent cytokine that mediates the
      development, differentiation, and neoplasm of the mammary gland. TGF beta1 is
      known to exert both tumor suppressive and progressive effect at different stages
      of carcinogenesis. Several studies have shown the association of TGF beta1
      expression with breast cancer markers like estrogen receptor (ER), progesterone
      receptor (PR), and Her2/neu. TGF beta1 expression is known to be influenced by 
      509C/T promoter polymorphism. Hence, the present study is aimed to evaluate the
      possible role of TGF beta1 -509C/T promoter polymorphism in breast cancer and its
      association with ER, PR, and Her2 status based on case-control study in South
      Indian population from Andhra Pradesh. Our study revealed a significant increase
      of CT genotype in breast cancer patients compared to controls (CT vs. CC: chi (2)
      = 6.054, P = 0.014, OR 2.005, 95 % CI 1.182-3.403). However, there was no
      correlation between TGF beta1 -509C/T polymorphism and other factors like age at
      onset, ER, PR, Her2 status, etc. Further, CT genotype was found to be associated
      with increased risk in advanced stages of breast cancer (CC vs. CT: OR 2.315, 95
      % CI 1.143-4.688) and a border line significance with postmenopausal women (CT
      vs. CC: chi (2) = 3.128, P = 0.07, OR 2.095, 95 % CI 0.991-4.428).

PMID- 23001909
TI  - Multicompartment intracellular self-expanding nanogel for targeted delivery of
      drug cocktail.
AB  - A nano cocktail, NCPD, fabricated from a pH and redox dual responsive polymer
      shows a multicompartment structure. The NCPD nanogel is stable in physiological
      environments while intracellular spontaneous swelling and fast releasing its
      payload. NCPD displays much stronger synergism than its free drug counterpart,
      which suggests that NCPD could greatly attenuate the side effects of drug
      cocktails while boosting synergistic anticancer effects.

PMID- 23001910
TI  - Eu(2+) luminescence in SrCaP2 O7 pyrophosphate phosphor.
AB  - A series of Eu(2+) activated SrCaP2 O7 pyrophosphate phosphors were synthesized
      by the modified solid-state reaction method. The X-ray diffraction (XRD) and
      photoluminescence (PL) properties of these phosphors were investigated at room
      temperature. The excitation spectra indicate that these phosphors can be
      effectively excited by Hg-free excitation. The emission spectra exhibit strong
      blue performance, which is due to the 4f(6) 5d(1) ->4f(7) transition of Eu(2+) .
      The Fourier transform infrared spectrum at room temperature was investigated and
      surface morphology has been studied by scanning electron microscope. The prepared
      phosphor exhibited intense blue emission at the 427 nm owing to Eu(2+) ion by Hg
      free excitation at 330 nm, that is, solid-state lighting excitation. Hence, the
      availability of such a phosphor will significantly help in the growth of blue
      emitting solid-state lighting applications.

PMID- 23001911
TI  - Follicular lymphoma: 2012 update on diagnosis and management.
AB  - DISEASE OVERVIEW: Follicular lymphoma (FL) is generally an indolent B-cell
      lymphoproliferative disorder of transformed follicular center B cells. FL is
      characterized by diffuse lymphoadenopathy, involvement of bone marrow,
      splenomegaly, and less commonly other extranodal sites of involvement. In
      general, cytopenias can occur but constitutional symptoms of fever, night sweats,
      and weight loss are uncommon. DIAGNOSIS: Diagnosis is based on histology of
      preferably a biopsy of a lymph node. Immunohistochemical staining is positive in
      virtually all cases for cell surface CD19, CD20, CD10, and monoclonal
      immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The
      overwhelming majority of cases have the characteristic t(14;18) translocation
      involving the IgH/bcl-2 genes. RISK STRATIFICATION: The FL International
      Prognostic Index prognostic model for FL uses five independent predictors of
      inferior survival: age > 60 years, hemoglobin < 12 g/dL, serum lactate
      dehydrogenase > normal, Ann Arbor stage III/IV, number of involved nodal areas >
      4. The presence of 0, 1, 2, and >= 3 adverse factors defines low, intermediate,
      and high-risk disease with median 10-year survivals in the pre-rituximab era of
      ~71, 51, and 36 months, respectively. With the use of more modern therapies,
      specifically anti-CD20 monoclonal antibody, the outcome has improved. RISK
      ADAPTED THERAPY: Observation continues to be adequate for asymptomatic patients
      with low bulk disease and no cytopenias. For patients needing therapy, most
      patients are treated with chemotherapy plus rituximab, which has improved
      response rates, duration of response, and overall survival. Randomized studies
      have shown additional benefit for maintenance rituximab both following
      chemotherapy-rituximab and single-agent rituximab. Autologous stem cell
      transplantation (SCT) has not shown a survival benefit in first remission
      patients. SCT including both autologous and allogeneic SCT or experimental agent
      therapy is considered for recurrent disease.

PMID- 23001912
TI  - Development of a rapid multiplex PCR assay for identification of the three common
      Hemoglobin-Lepore variants (Boston-Washington, Baltimore, and Hollandia) and
      identification of a new Lepore variant.

PMID- 23001913
TI  - Multicomponent assembly of highly substituted indoles by dual palladium-catalyzed
      coupling reactions.
AB  - Highly substituted indoles were synthesized by a palladium-catalyzed reaction
      involving three independent components in a one-pot reaction. Two distinct
      palladium-catalyzed coupling reactions occur with a single catalytic system: a
      Buchwald-Hartwig reaction and an arene-alkene coupling. Quantum chemical
      computations provide insight into the mechanism of the latter coupling step.

PMID- 23001914
TI  - Effects of bleaching agents and Tooth Mousse(TM) on human enamel hardness.
AB  - OBJECTIVE: The aim of this laboratory study was to investigate the effect of
      three commercial bleaching agents and Tooth Mousse(TM) containing 10% w/w casein
      phosphopeptide-amorphous calcium phosphate on the hardness of tooth enamel.
      METHODS: Sixteen human enamel specimens were exposed to one of three commercial
      bleaching agents with or without subsequent exposure to Tooth Mousse(TM) .
      Nanoindentation was used to measure the hardness and reduced modulus before and
      after treatments. RESULTS: When bleaching materials were applied for a short
      period of time following the manufacturers' instructions, there was an increase
      in enamel hardness and reduced modulus for some bleaching groups, with no
      statistically significant difference from the baseline values. After extended
      bleaching periods a statistically significant decrease in enamel hardness and
      reduced modulus was found and after applying Tooth Mousse(TM) post-bleaching, the
      hardness and reduced modulus returned to close to baseline values. CONCLUSION:
      The application of bleaching agents for an extended period of time significantly
      decreases enamel hardness and the reduced modulus. The application of Tooth
      Mousse(TM) after bleaching was able to reestablish the baseline enamel hardness
      and reduced modulus, decreasing the adverse effects of bleaching enamel.

PMID- 23001915
TI  - Simultaneous determination of phenolic compounds and triterpenic acids in oregano
      growing wild in Greece by 31P NMR spectroscopy.
AB  - (31)P nuclear magnetic resonance (NMR) spectroscopy was used to detect and
      quantify simultaneously a large number of phenolic compounds and the two
      triterpenic acids, ursolic acid and oleanolic acid, extracted from two oregano
      species Origanum onites and Origanum vulgare ssp. Hirtum using two different
      organic solvents ethanol and ethyl acetate. This analytical method is based on
      the derivatization of the hydroxyl and carboxyl groups of these compounds with
      the phosphorous reagent 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxa phospholane and
      the identification of the phosphitylated compounds on the basis of the (31)P
      chemical shifts. Unambiguous assignment of the (31)P NMR chemical shifts of the
      dihydroxy- and polyhydroxy-phenols in oregano species as well as those of the
      triterpenic acids was achieved upon comparison with the chemical shifts of model
      compounds assigned by using two-dimensional NMR techniques. Furthermore, the
      integration of the appropriate signals of the hydroxyl derivatives in the
      corresponding (31)P NMR spectra and the use of the phosphitylated cyclohexanol as
      an internal standard allowed the quantification of these compounds. The validity
      of this technique for quantitative measurements was thoroughly examined.

PMID- 23001916
TI  - Conceptual underestimation of the total body clearance by the sum of clearances
      of individual organs in physiologically based pharmacokinetics.
AB  - It is commonly assumed for linear pharmacokinetics that the total body clearance
      (CL) is equal to the sum of clearances of individual elimination organs. This is
      not quite valid because, in general, the concentration of drug in arterial blood
      entering the elimination organ is not the same as the measured venous blood
      concentration that is used to calculate CL. Consideration of physiologically
      based pharmacokinetic model that differentiates between venous and arterial blood
      shows that CL exceeds the sum of clearances provided by individual organs.
      Assuming liver as the only elimination organ, it was found that the
      underestimation of CL by the sum of clearances of individual elimination organs
      would not exceed 35% for mammals. The underestimation of CL would be more
      pronounced for high extraction ratio drugs. Thus, for the case when in vivo
      measured CL considerably exceeds the in vitro predictions (assuming that they
      provide the organ clearances correctly), a possible reason for discrepancy could
      be the initial nonlinear phase of drug distribution and excretion. Probably, at
      this stage a substantial amount of drug is eliminated before distribution into
      the organs and tissues.

PMID- 23001918
TI  - Expression of the irisin precursor FNDC5 in skeletal muscle correlates with
      aerobic exercise performance in patients with heart failure.
AB  - BACKGROUND: Exercise-induced increase in peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha (PGC-1alpha) expression has been shown to
      increase the expression of the fibronectin type III domain containing 5 (FNDC5)
      gene and thereby its product, irisin, in mice. Given that exercise intolerance is
      a hallmark characteristic of heart failure (HF), and because PGC-1alpha and
      irisin promote exercise benefits in animals, we hypothesized that expression of
      these genes relates to aerobic performance in patients with HF. METHODS AND
      RESULTS: Systolic HF (left ventricular ejection fraction <=40%) patients
      underwent cardiopulmonary exercise testing to evaluate aerobic performance. High
      versus low aerobic performance was assessed using oxygen consumption (peak Vo(2)
      [>14 versus <=14 mL O(2).kg(-1).min(-1)]) and ventilatory efficiency (VE/Vco(2)
      slope [<34 versus >=34]). Muscle biopsies of the vastus lateralis and real-time
      polymerase chain reaction were used to quantify muscle gene expression. Twenty
      four patients were studied. FNDC5 (5.7+/-3.5 versus 3.1+/-1.2, P<0.05) and PGC
      1alpha (9.9+/-5.9 versus 4.5+/-1.9, P<0.01) gene expressions were greater in the
      high-peak Vo(2) group; correlation between FNDC5 and PGC-1alpha was significant
      (r=0.56, P<0.05) only in the high-peak Vo(2) group. Similarly, FNDC5 and PGC
      1alpha gene expression was greater in the high-performance group based on lower
      VE/Vco(2) slopes (5.8+/-3.6 versus 3.3+/-1.4, P<0.05 and 9.7+/-6 versus 5.3+/
      3.4, P<0.05); FNDC5 also correlated with PGC-1alpha (r=0.55, P<0.05) only in the
      low VE/Vco(2) slope group. CONCLUSIONS: This is the first study to show that
      FNDC5 expression relates to functional capacity in a human HF population. Lower
      FNDC5 expression may underlie reduced aerobic performance in HF patients.

PMID- 23001917
TI  - Brains, bones, and aging: psychotropic medications and bone health among older
      adults.
AB  - Psychotropic drugs are a crucial element of treatment for psychiatric disorders;
      however there is an established association between many classes of psychotropic
      medications and fracture risk among older adults, and growing evidence that some
      classes of medications may also impact bone mineral density (BMD). In this paper
      we review recent epidemiologic research on the association between psychotropic
      medications and osteoporosis, and discuss current controversies and unresolved
      issues surrounding this relationship. Key areas in need of focused inquiry
      include resolving whether the apparent association between psychotropic
      medications and BMD is due to confounding by indication, whether this
      relationship differs for men and women, and whether the implications of these
      medications for bone health vary over the life course. Clinical research to
      delineate the risk/benefit ratio of psychotropic medications for older adults,
      particularly those who are at high risk for fracture, is also needed to
      facilitate prescribing decisions between patients and physicians.

PMID- 23001919
TI  - Ethical considerations in targeted paediatric neurosurgery missions.
AB  - Within the context of global health development approaches, surgical missions to
      provide care for underserved populations remain the least studied interventions
      with regard to their methodology. Because of the unique logistical needs of
      delivering operative care, surgical missions are often described solely in terms
      of cases performed, with a paucity of discourse on medical ethics. Within
      surgery, subspecialties that serve patients on a non-elective basis should, it
      could be argued, create mission strategies that involve a didactic approach and
      the propagation of sustainable surgical care. The ethical considerations have yet
      to be described for paediatric neurosurgical outreach missions. We present here
      the perspectives of neurosurgeons who have participated in surgical outreach
      missions in Central America, South America, Eastern Europe and sub-Saharan Africa
      from the vantage point of both the visiting mission team and the host team that
      accommodates the mission efforts.

PMID- 23001920
TI  - A legal market in organs: the problem of exploitation.
AB  - The article considers the objection to a commercial market in living donor organs
      for transplantation on the ground that such a market would be exploitative of the
      vendors. It examines a key challenge to that objection, to the effect that
      denying poor people the option to sell an organ is to withhold from them the best
      that a bad situation has to offer. The article casts serious doubt on this
      attempt at justifying an organ market, and its philosophical underpinning.
      Drawing, in part, from the catalogued consequences of a thriving kidney market in
      some parts of India, it is argued that the justification relies on conditions
      which are extremely unlikely to obtain, even in a regulated donor market: that
      organ selling meaningfully improves the material situation of the organ vendor.
      Far from being axiomatic, both logic and the extant empirical evidence point
      towards the unlikelihood of such an upshot. Finally, the article considers a few
      conventional counter-arguments in favour of a permissive stance on organ sales. 

PMID- 23001921
TI  - Might stimulant drugs support moral agency in ADHD children?
AB  - Stimulants have been shown to be safe and effective for reduction of the symptoms
      of attention deficit hyperactivity disorder. Despite much debate, however, there
      has been little empirical evidence as to whether stimulants affect authenticity
      and moral agency in children. Singh presents evidence that stimulants do not
      undercut children's' sense of self and increase their experience of agency. These
      findings are consistent with laboratory evidence that stimulant drugs in
      therapeutic doses improve cognitive control over thought and behavior.

PMID- 23001922
TI  - Removal of endotoxins from plasmid DNA: analysis of aggregative interaction of
      mobile divalent metal cations with endotoxins and plasmid DNA.
AB  - Endotoxin lipopolysaccharide removal from plasmid DNA-based vaccine remains a
      very challenging task for bioprocess engineers. This paper examined the potential
      use and advantages of divalent cation (Zn(2+), Ca(2+), Mg(2+)) induced
      aggregation as a plasmid DNA purification method for lipopolysaccharide removal.
      Analysis of zeta potential, hydrodynamic size, percentage of aggregation; UV-Vis
      spectroscopy and electron microscopy were performed to determine the optimal
      cation for preferential aggregation of lipopolysaccharide over plasmid DNA. The
      results from the hydrodynamic size analysis showed that the addition of Zn(2+)
      resulted in the maximum theoretical number of lipopolysaccharide molecules per
      aggregate particle. Dynamic light scattering analysis showed that plasmid DNA
      aggregates formed a larger maximum hydrodynamic size when it was treated with
      Ca(2+) than the other two cations. The K(m) value for lipopolysaccharide-Zn(2+)
      was substantially low (0.28 M) and considerably large (>2 M) for plasmid DNA
      Zn(2+). Scatchard plots for plasmid DNA cations showed positive slopes indicating
      that there was a minimum concentration of plasmid DNA or cations before a
      significant aggregation occurred. This work concluded that Zn(2+) had the most
      preferential aggregative interaction with lipopolysaccharide compared to Mg(2+)
      and Ca(2+).

PMID- 23001923
TI  - Isolated pulmonary Langerhans cell histiocytosis.
AB  - Isolated pulmonary involvement in Langerhans Cell Histiocytosis (LCH) is rare in
      childhood. The authors report a 6-y- old boy presenting with recurrent
      pneumothorax, whose CT thorax showed diffuse pulmonary cystic lucencies
      bilaterally. Biopsy of the lesions confirmed pulmonary LCH with Cd1a and S 100
      positivity.

PMID- 23001924
TI  - Risk of malignancy in unilocular cysts: a study of 1148 adnexal masses classified
      as unilocular cysts at transvaginal ultrasound and review of the literature.
AB  - OBJECTIVES: The aim of this study was to estimate the rate of malignancy in
      adnexal lesions described as unilocular cysts at transvaginal ultrasound
      examination and to investigate if there are differences in clinical and
      ultrasound characteristics between benign and malignant unilocular cysts.
      METHODS: A total of 3511 patients with an adnexal mass underwent transvaginal
      ultrasound examination between 1999 and 2007. Sonologists used the International
      Ovarian Tumor Analysis terms and definitions to describe their ultrasound
      findings. Only masses operated on within 120  days after the ultrasound
      examination were included in the analysis and the histopathological diagnosis of
      the mass was used as the gold standard. RESULTS: Of the 3511 masses, 1148 (33%)
      were classified as unilocular cysts on ultrasound. Of these, 11 (0.96% (95% CI,
      0.48-1.71)) were malignant. The malignancy rate was lower in premenopausal than
      in postmenopausal women: 0.54% (5/931; 95% CI, 0.17-1.25) vs. 2.76% (6/217; 95%
      CI, 1.02-5.92); P = 0.009. More patients with malignant unilocular cysts had a
      personal history of breast cancer (18% vs. 2%; P = 0.02) or ovarian cancer (18%
      vs 0.6%; P = 0.003). Hemorrhagic cyst contents on ultrasound were more common in
      malignant than in benign unilocular cysts (18% vs. 2%; P = 0.03). In seven of the
      11 malignancies judged to be unilocular cysts at scan, papillary projections or
      other solid components were seen at macroscopic inspection of the surgical
      specimen. CONCLUSIONS: The malignancy rate in surgically removed adnexal lesions
      judged to be unilocular cysts at transvaginal scan is c 1%. Postmenopausal
      status, personal history of breast or ovarian cancer and hemorrhagic cyst
      contents on ultrasound increase the risk of malignancy. To avoid misclassifying
      adnexal lesions as unilocular cysts at scan, it is important to scrutinize
      unilocular cysts for the presence of solid components.

PMID- 23001925
TI  - The role of CCND1 alterations during the progression of cutaneous malignant
      melanoma.
AB  - It is well demonstrated that CCND1 amplification is a frequent event in the acral
      subtype of cutaneous malignant melanoma; however, its role in the other subtypes
      of the disease is still controversial. The objectives of this study were to
      evaluate genetic and expression alterations of CCND1 with a focus on primary
      cutaneous melanomas, to define BRAF and NRAS mutation status, and correlate the
      data with clinical-pathological parameters. CCND1 amplification was associated
      with ulceration and the localization of the metastasis. After correction for the
      mutation state of BRAF and NRAS genes, CCND1 amplification in samples without
      such mutations was associated with ulceration and sun exposure. The cyclin D1
      (CCND1) mRNA level decreased in lesions with multiple metastases and was
      correlated with both the mRNA levels and mutation state of BRAF and NRAS genes.
      Primary melanomas with BRAF(V600) or NRAS(Q61 ) mutations exhibited lower CCND1
      mRNA level. CCND1 protein expression was associated with Breslow thickness,
      metastasis formation, and shorter survival time. These observations suggest that
      CCND1 alterations are linked to melanoma progression and are modified by BRAF and
      NRAS mutations. Our data show that CCND1 amplification could have a prognostic
      relevance in cutaneous melanoma and highlight that altered CCND1 gene expression
      may influence the metastatic progression, survival, and the localization of
      metastases.

PMID- 23001926
TI  - Overexpression and cytoplasmic accumulation of Hepl is associated with
      clinicopathological parameters and poor prognosis in non-small cell lung cancer.
AB  - Hepl, first described in 2008, is the fourth member of the Crk-associated
      substrate (CAS) family and is specifically expressed in the lung. Compared to
      other CAS proteins, Hepl has a varying effect on cell migration in different cell
      types. We speculated that Hepl may play a role in lung cancer invasion and
      metastasis. We quantified the expression and subcellular localization of Hepl in
      143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues,
      and eight lung cancer cell lines using Western blotting, immunohistochemistry,
      and immunofluorescent staining. Expression of Hepl was correlated with the
      clinicopathological features of NSCLC. Hepl was overexpressed in 72.3 % (103/143)
      of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P =
      0.022). Overexpression of Hepl was associated with lymph node metastasis and high
      TNM stage (P = 0.005 and P = 0.045, respectively). Kaplan-Meier survival curves
      and the log-rank test indicated that overexpression of Hepl correlated with
      poorer overall survival in NSCLC (P < 0.001), and Cox regression analysis
      demonstrated that overexpression of Hepl was an independent prognostic factor in
      NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high
      metastatic potential lung cancer cell lines (H1299 and BE1), but not in low
      metastatic potential cell lines (LTE and A549). This study reveals that Hepl is
      overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC
      cells, and indicates that Hepl may play a role in the progression of lung cancer,
      including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful
      prognostic factor in lung cancer.

PMID- 23001927
TI  - Proteins linked to drought tolerance revealed by DIGE analysis of drought
      resistant and susceptible barley varieties.
AB  - Drought is a major threat to world agriculture. In order to identify proteins
      associated with plant drought tolerance, barley varieties bred in the UK (Golden
      Promise) and Iraq (Basrah) were compared. The variety Basrah showed physiological
      adaptations to drought when compared to Golden Promise, for example relative
      water content of roots and shoots after 1 week of drought was much higher for
      Basrah than for Golden Promise. DIGE analysis was carried out on proteins from
      roots and leaves under control and drought conditions. Twenty-four leaf and 45
      root proteins were identified by MALDI-TOF MS. The relative expression patterns
      of the identified proteins fell into a number of distinct classes. The variety
      Basrah is characterised by constitutive expression or higher drought-induced
      expression levels of proteins regulating ROS production and protein folding.
      Photosynthetic enzymes, by contrast, were downregulated in Basrah. Enzyme assays
      showed a good correlation between DIGE-derived protein abundance estimates and
      enzyme activity in extracts. Overall, this study shows that the enhanced drought
      tolerance of variety Basrah is driven by an enhanced regulation of ROS under
      drought.

PMID- 23001928
TI  - Influence of alkyl chain branching positions on the hole mobilities of polymer
      thin-film transistors.
AB  - Four polymers that contain alkyl chains branched at different positions on the
      polymer backbone are prepared. A polymer with 4-decyltetradecyl chains gives an
      impressive mobility of 3.62 cm(2)  V(-1)  s(-1) . This may arise from tighter
      polymer packing as well as stacking conformation change of the polymer backbone
      induced by the branching of the alkyl chains.

PMID- 23001929
TI  - Epilepsy characteristics and psychosocial factors associated with ketogenic diet
      success.
AB  - The ketogenic diet is an effective therapy for childhood epilepsy, but its
      important impacts on families could affect successful treatment. We assessed
      medical and psychosocial factors associated with successful ketogenic diet
      treatment. A total of 23 families of patients treated with ketogenic diet
      completed questionnaires (30% response), including inquiries about challenges to
      successful dietary treatments and validated family functioning scales. Of these,
      14 were considered successful (diet discontinued once the child was seizure-free
      or continued as clinically indicated). Family-identified challenges were food
      preparation time (n = 11) and that the diet was too restrictive (n = 9). Neither
      Medicaid insurance nor family functioning scale scores were significantly
      associated with successful treatment. Lower seizure frequency prior to ketogenic
      diet initiation (P = .02) and postdiet seizure improvement (P = .01) were
      associated with increased odds of success. Effective ketogenic diet treatment is
      dictated both by psychosocial and epilepsy-related influences. A focus on
      understanding the psychosocial issues may help to improve families' experiences
      and success with the ketogenic diet. 

PMID- 23001931
TI  - Hope is a virtue.
AB  - Understanding the meaning and importance of what constitutes hope when counseling
      members of a family and their child in a medical setting is a vital skill for
      physicians. The hope that the physicians must foster is that they will offer
      comfort and care, honesty and availability, and genuine expertise. Although there
      is no obligation to sustain harmful treatments to maintain false hopes, there is
      also no obligation to extinguish hope in parents and patients for the outcome of
      a disorder.

PMID- 23001930
TI  - Brainstem cavernoma hemorrhage during pregnancy in a 15-year-old: description of
      a unique neurosurgical approach.
AB  - Cavernous haemangiomas, or cavernous malformations, have been reported during
      pregnancy, most of which have been either supratentorial or spinal lesions. We
      encountered a 15-year old pregnant patient with a rapidly progressive and
      haemorrhagic brainstem cavernous haemangioma. The case presented here describes
      the history and findings of this patient, as well as the less-commonly utilized
      technique we used to access the floor of the fourth ventricle via occipital
      craniotomy for complete macroscopic resection of this lesion, resulting in the
      gradual return of most of her neurological deficits. 

PMID- 23001932
TI  - Heterobinuclear Zn-Ln (Ln = La, Nd, Eu, Gd, Tb, Er and Yb) complexes based on
      asymmetric Schiff-base ligand: synthesis, characterization and photophysical
      properties.
AB  - With a novel asymmetric Schiff-base zinc complex ZnL (H2 L = N-(3
      methoxysalicylidene)-N'-(5-bromo-3-methoxysalicylidene)phenylene-1,2-diamine),
      obtained from phenylene-1,2-diamine, 3-methoxysalicylaldehyde and 5-bromo-3
      methoxysalicylaldehyde, as the precursor, a series of heterobinuclear Zn-Ln
      complexes [ZnLnL(NO3 )3 (CH3 CN)] (Ln = La, 1; Ln = Nd, 2; Ln = Eu, 3; Ln = Gd,
      4; Ln = Tb, 5; Ln = Er, 6; Ln = Yb, 7) were synthesized by the further reaction
      with Ln(NO3 )3 .6H2 O, and characterized by Fourier transform-infrared, fast atom
      bombardment mass spectroscopy and elemental analysis. Photophysical studies of
      these complexes show that the strong and characteristic near-infrared
      luminescence of Nd(3+) , Yb(3+) and Er(3+) with emissive lifetimes in the
      microsecond range has been sensitized from the excited state of the asymmetric
      Schiff-base ligand due to effective intramolecular energy transfer; the other
      complexes do not show characteristic emission due to the energy gap between the
      chromophore and lanthanide ions.

PMID- 23001933
TI  - Effects of the peroxisome proliferator di(2-ethylhexyl)phthalate on cell turnover
      and peroxisome proliferation in primary chick embryo hepatocytes.
AB  - The peroxisome proliferator (PP) di(2-ethylhexyl)phthalate (DEHP) is widely used
      as a plasticizer and can contaminate air, water, and soil. As yet, no data have
      been published on its potential to induce changes in cell growth of nonmammalian
      hepatocytes. In the present study, the effects of DEHP on cell turnover and
      induction of peroxisome proliferation were evaluated in primary hepatocyte
      cultures from chick embryos. Cells were treated after attachment with 0, 25, 50,
      75, and 100 uM DEHP for up to 96 h. S-phase increased significantly (p < 0.01)
      from a background level of 5.5 +/- 0.1% in solvent-control hepatocytes to a
      maximum level of 7.1 +/- 0.1% in cells exposed for 48 h to 100 uM DEHP and
      decreased to near 6% by 96 h. Lower (p < 0.05) levels of induction were seen at
      50 and 75 uM DEHP. Spontaneous apoptosis showed a slight (p < 0.05) decrease in
      hepatocytes treated with >=75 uM dosages, as measured at 72 to 96 h. Induction of
      peroxisome proliferation was observed for cultures treated with >=75 uM dosages
      at 48 h onwards. The results of the present study indicate that avian species may
      be responsive to the effects of PPs and may thus be affected by the presence of
      DEHP in the environment, but that this species is less sensitive than rodents.

PMID- 23001934
TI  - Nano- and microsized cubic gel particles from cyclodextrin metal-organic
      frameworks.
AB  - Sweet cube o' mine: Bottom-up control of gel particles has been regarded as a
      great challenge. By employing internal cross-linking of cyclodextrin metal
      organic frameworks, cubic sugar gels were formed with sharp edges that reflect
      the shape of the crystals. This enabled the fabrication of shape- and size
      controlled polymer gels from porous crystals (see picture).

PMID- 23001935
TI  - Reversible pseudoathetosis induced by cervical myelopathy.

PMID- 23001936
TI  - Commentary for reversible pseudoathetosis induced by cervical myelopathy.

PMID- 23001937
TI  - Acute parkinsonism in Cryptococcus gattii meningoencephalitis: extensive lesions
      in basal ganglia.

PMID- 23001938
TI  - Cryosurgery of the oral and peri-oral region: a literature review of the
      mechanism, tissue response, and clinical applications.
AB  - Cryosurgery is a method of achieving lesion destruction by rapid freezing in
      situ. Application of cryosurgery in medicine widespread and its use within
      dentistry is also well documented, using both open and closed liquid nitrogen and
      carbon dioxide. The major advantages of oral cryosurgery include bloodless
      treatment, very low incidence of secondary infection, and a relative lack of
      scarring and pain. This review outlines knowledge on the mechanisms, tissue
      response, and current practices of cryosurgery in the oral and peri-oral region.
      More experimental studies are needed to better understand this important modality
      at cellular and molecular levels. Inconsistency in the current protocols used for
      the treatment of the oral lesions is evident. Additional studies are needed to
      define the treatment protocols for different types of oral lesions. Information
      on the cryogen type and dose and the delivery technique required would help to
      produce reproducible outcomes for the treatment of targeted lesions.

PMID- 23001939
TI  - Cognitive enhancement and neuroprotection by catechin-rich oil palm leaf extract
      supplement.
AB  - BACKGROUND: Catechin-rich oil palm (Elaeis guineensis) leaf extract (OPLE) has
      good cardiovascular and phytoestrogenic properties. The OPLE (0.5 g day(-1) ) was
      supplemented to young, healthy, adult human volunteers, and their cognitive
      learning abilities were compared to placebo-controlled groups (N = 15). Their
      short-term memories, spatial visualisations, processing speeds, and language
      skills, were assessed over 2 months by cognitive tests computer programs.
      RESULTS: Relative to the controls, volunteers taking OPLE had improved (P < 0.05)
      short-term memory, after 1 month of intervention which became highly significant
      (P < 0.005) after 2 months. The spatial visualisation ability and processing
      speed improved (P < 0.05) after 2 months consumption. The dietary OPLE showed
      neuroprotection in nitric oxide-deficient rats. The mechanisms involved systemic
      and cellular modulations that eventually enhance neuron survival. The longer the
      duration of OPLE consumption, the more significant was the enhancement, as shown
      for short-term memory. CONCLUSION: This is the first report on the cognitive
      enhancing effects of dietary OPLE in humans. The computer-assisted cognitive
      tests were simple, low in cost, errors and man hours, and hence are better than
      conventional cognitive test methods. In rats, the equivalent OPLE dose showed
      brain antioxidant enzymes modulating properties and neuroprotection under nitric
      oxide deficiency, with possibly neurogenesis in normal rats. This supported the
      effects in humans.

PMID- 23001940
TI  - Ionic liquid-based microwave-assisted extraction for the determination of
      flavonoid glycosides in pigeon pea leaves by high-performance liquid
      chromatography-diode array detector with pentafluorophenyl column.
AB  - In this study, an ionic liquid-based microwave-assisted extraction (ILMAE)
      followed by high-performance liquid chromatography-diode array detector with a
      pentafluorophenyl column for the extraction and quantification of eight flavonoid
      glycosides in pigeon pea leaves is described. Compared with conventional
      extraction methods, ILMAE is a more effective and environment friendly method for
      the extraction of nature compounds from herbal plants. Nine different types of
      ionic liquids with different cations and anions were investigated. The results
      suggested that varying the anion and cation had significant effects on the
      extraction of flavonoid glycosides, and 1.0 M 1-butyl-3-methylimidazolium bromide
      ([C4MIM]Br) solution was selected as solvent. In addition, the extraction
      procedures were also optimized using a series of single-factor experiments. The
      optimum parameters were obtained as follows: extraction temperature 60 degrees C,
      liquid-solid ratio 20:1 mL/g and extraction time 13 min. Moreover, an HPLC method
      using pentafluorophenyl column was established and validated. Good linearity was
      observed with the regression coefficients (r(2)) more than 0.999. The limit of
      detection (LODs) (S/N = 3) and limit of quantification (LOQs) (S/N = 10) for the
      components were less than 0.41 and 1.47 MUg/mL, respectively. The inter- and
      intraday precisions that were used to evaluate the reproducibility and relative
      standard deviation (RSD) values were less than 4.57%. The recoveries were between
      97.26 and 102.69%. The method was successfully used for the analysis of samples
      of pigeon pea leaves. In conclusion, the developed ILMAE-HPLC-diode array
      detector using pentafluorophenyl column method can be applied for quality control
      of pigeon pea leaves and related medicinal products.

PMID- 23001941
TI  - Estimated cardiac output and cardiovascular profile score in fetuses with high
      cardiac output lesions.
AB  - OBJECTIVE: High cardiac output lesions are associated with an increased risk of
      fetal death, largely as a result of cardiac failure and hydrops fetalis. The
      cardiovascular profile score (CVPS) has been used to characterize cardiovascular
      wellbeing, and has been linked to fetal outcomes in other conditions. We aimed to
      test the hypothesis that elevated combined cardiac output (CCO) in fetuses with
      high output lesions may be associated with worsening cardiovascular status, as
      evidenced by a lower CVPS. METHODS: A retrospective review was performed of
      fetuses with high cardiac output lesions that underwent echocardiography between
      July 2006 and November 2010. Diagnoses included sacrococcygeal teratoma,
      placental chorioangioma and vein of Galen aneurysm. Fetal echocardiographic
      evaluation included assessment of CVPS, as well as Doppler/two-dimensional
      estimation of CCO, indexed to estimated fetal weight (CCOi). The relationship
      between CCO and CVPS was assessed. RESULTS: A total of 35 fetuses were studied:
      27 had sacrococcygeal teratoma, seven had chorioangioma and one had vein of Galen
      aneurysm. There was a significant inverse relationship between mean logCCOi and
      CVPS (r2  = 0.48, P = 0.008). Of 31 patients with clinical outcome data, 10
      experienced either in-utero demise or intervention; 80% of these fetuses had a
      CVPS of < 8. CONCLUSIONS: There is an inverse relationship between CCO and CVPS
      in the fetus with high cardiac output lesions. As a measure of fetal
      cardiovascular wellbeing in this population, the CVPS may be a useful tool for
      stratifying risk and for selection for intervention in these fetuses.

PMID- 23001942
TI  - Persistence and changes in bioavailability of dieldrin, DDE, and heptachlor
      epoxide in earthworms over 45 years.
AB  - The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19
      ng/g) in earthworms from experimental plots after a single moderate application
      (9 kg/ha) 45 years earlier attests to the remarkable persistence of these
      compounds in soil and their continued uptake by soil organisms. Half-lives (with
      95 % confidence intervals) in earthworms, estimated from exponential decay
      equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1)
      years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not
      significantly different from those estimated after 20 years. Concentration
      factors (dry weight earthworm tissue/dry weight soil) were initially high and
      decreased mainly during the first 11 years after application. By the end of the
      study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8
      (heptachlor epoxide), respectively.

PMID- 23001943
TI  - 'Fishing' for alternatives to mountaintop mining in southern West Virginia.
AB  - Mountaintop removal mining (MTR) is a major industry in southern West Virginia
      with many detrimental effects for small to mid-sized streams, and interest in
      alternative, sustainable industries is on the rise. As a first step in a larger
      effort to assess the value of sport fisheries in southern West Virginia, we
      estimate the potential abundances of two popular sport fishes-smallmouth bass
      (Micropterus dolomieu) and brook trout (Salvelinus fontinalis)-in the Coal River
      Basin (CRB). A self-thinning model that incorporates net primary production and
      terrestrial insect subsidies is first used to predict potential densities of
      adult (age 1+) smallmouth bass and brook trout. Predicted densities (fish ha(-1))
      are then multiplied by the surface area of the CRB stream network (ha) to
      estimate regional abundance. Median predicted abundances of bass and trout are 38
      806 and 118 094 fish (total abundances with the CRB), respectively. However, when
      streams that intersect permitted MTR areas in the CRB are removed from the
      dataset, predicted abundances of bass and trout decrease by ~12-14 %. We conclude
      that significant potential exists in the CRB to capitalize on sport fisheries,
      but MTR may be undermining this potential.

PMID- 23001944
TI  - Drivers of forest cover dynamics in smallholder farming systems: the case of
      northwestern Vietnam.
AB  - The national-scale forest recovery of Vietnam started in the early 1990s and is
      associated with a shift from net deforestation to net reforestation. Large
      disparities in forest cover dynamics are, however, observed at the local scale.
      This study aims to unravel the mechanisms driving forest cover change for a
      mountainous region located in northwest Vietnam. Statistical analyses were used
      to explore the association between forest cover change and household
      characteristics. In Sa Pa district, deforestation rates are decreasing, but
      forest degradation continues at similar rates. Deforestation is not necessarily
      associated with impoverished ethnic communities or high levels of subsistence
      farming, and the largest forest cover dynamics are found in villages with the
      best socio-economic conditions. Our empirical study does not provide strong
      evidence of a dominant role of agriculture in forest cover dynamics. It shows
      that empirical studies on local-scale forest dynamics remain important to unravel
      the complexity of human-environment interactions.

PMID- 23001945
TI  - The energy for growing and maintaining cities.
AB  - Herein we develop a means to differentiate between the energy required to expand
      and the energy required to maintain the economies of cities. A nonlinear model is
      tested against historical data for two cities, Hong Kong and Singapore. A robust
      fit is obtained for Hong Kong, with energy for maintenance close to that for
      growth, while Singapore, with a weaker fit, is growth dominated. The findings
      suggest that decreases in either of the per unit maintenance or growth demands
      can simultaneously cause gross domestic product (GDP) and total energy use to
      increase. Furthermore, increasing maintenance demands can significantly limit
      growth in energy demand and GDP. Thus, the low maintenance demands for Hong Kong,
      and especially Singapore, imply that, all other things being equal, GDP and
      energy use of these cities will continue to grow, though Singapore's higher
      energy use for growth means it will require more energy than Hong Kong.

PMID- 23001946
TI  - 1H, 13C and 15N assignments of Sgt2 N-terminal dimerisation domain and its
      binding partner, Get5 Ubiquitin-like domain.
AB  - The first stage of the GET (guided entry of tail-anchored proteins) mechanism for
      tail-anchored (TA) membrane protein insertion is thought to occur when Sgt2
      (small, glutamine-rich, tetratricopeptide repeat-containing protein 2) binds TA
      proteins upon their release from the ribosome. It sorts them and passes the
      majority over to a complex of Get5 and Get4 for transmission along the GET
      pathway and delivery to their membrane destination. Sgt2 is a 38 kDa protein
      consisting of three domains. The N-terminal domain effects tight dimerisation of
      the protein and is also the site for binding with the ubiquitin-like (UBL) domain
      of Get5. Here we have expressed and purified uniformly-(15)N/(13)C-labelled N
      terminal Sgt2 (Sgt2_NT) and its binding partner, Get5 UBL domain (Get5_UBL) and
      assigned the backbone and side-chain resonances as a basis for structure solution
      of the individual components and, ultimately, the complex. This will provide
      detailed molecular insight into the early stages of the GET pathway. 

PMID- 23001947
TI  - Backbone resonance assignments of the homotetrameric (48 kD) copper sensor CsoR
      from Geobacillus thermodenitrificans in the apo- and Cu(I)-bound states: insights
      into copper-mediated allostery.
AB  - Prokaryotes are highly susceptible to exogenous copper and employ
      metalloregulatory proteins to control the intracellular concentration. CsoR
      (copper-sensitive operon repressor) is one such protein that represses
      transcription of a Cu(I)-effluxing ATPase in its apo form. Cu(I)-binding leads to
      transcriptional derepression and cellular copper resistance. Herein, we present
      substantially complete backbone (H(N), N, C', Calpha, Cbeta) resonance
      assignments of tetrameric (48 kD) Geobacillus thermodenitrificans (Gt) CsoR in
      its apo- and Cu(I)-saturated states. These data provide the first spectroscopic
      evidence that Cu(I)-binding induces an interruption in the long alpha2 helix of
      CsoR. 

PMID- 23001948
TI  - Polymorphonuclear neutrophils promote dyshesion of tumor cells and elastase
      mediated degradation of E-cadherin in pancreatic tumors.
AB  - Pancreatic ductal adenocarcinoma (PDAC) presenting with a micropapillary growth
      pattern is frequently associated with a prominent neutrophil infiltration into
      the tumor. The relevance of neutrophil infiltrates for tumor progression,
      however, is still debated. To gain insight into the role of polymorphonuclear
      neutrophils (PMNs) in PDAC, we assessed their effect on pancreatic tumor cells
      grown in vitro as monolayers. Time-lapse video microscopy showed a PMN-induced
      dyshesion of the tumor cells, and subsequent experiments revealed that this
      dyshesion was due to PMN elastase-mediated degradation of E-cadherin, an adhesion
      molecule that mediates the intercellular contact of the tumor cells. E-cadherin
      degradation by elastase or--(for comparison) down-modulation by specific siRNA,
      significantly increased the migratory capacity of the pancreatic tumor cells,
      leading to the hypothesis that PMNs could contribute to the invasive tumor
      growth. To address this issue, biopsies of patients with PDAC (n = 112) were
      analyzed. We found that E-cadherin expression correlated negatively with PMN
      infiltration, compatible with the notion that E-cadherin is cleaved by PMN
      derived elastase, which in turn could result in the dispersal of the tumor cells,
      enhanced migratory capacity and thus invasive tumor growth.

PMID- 23001949
TI  - Medicine, the media and political interests.
AB  - The news media is frequently criticised for failing to support the goals of
      government health campaigns. But is this necessarily the purpose of the media? We
      suggest that while the media has an important role in disseminating health
      messages, it is a mistake to assume that the media should serve the interests of
      government as it has its own professional ethics, norms, values, structures and
      roles that extend well beyond the interests of the health sector, and certainly
      beyond those of the government. While considerable attention has been given to
      the ways in which uncritical publication of industry perspectives by news media
      can negatively impact on public understandings of health and health behaviours,
      we would argue that it is equally important that journalists not become the
      'lapdogs' of government interests. Further, we suggest that the interests of
      public health may be served more by supporting the ongoing existence of an
      independent media than by seeking to overdetermine its purpose or scope.

PMID- 23001950
TI  - High performance ambipolar field-effect transistor of random network carbon
      nanotubes.
AB  - Ambipolar field-effect transistors of random network carbon nanotubes are
      fabricated from an enriched dispersion utilizing a conjugated polymer as the
      selective purifying medium. The devices exhibit high mobility values for both
      holes and electrons (3 cm(2) /V.s) with a high on/off ratio (10(6) ). The
      performance demonstrates the effectiveness of this process to purify
      semiconducting nanotubes and to remove the residual polymer.

PMID- 23001951
TI  - Secular changes in BMI and the associations between risk factors and BMI in
      children born 29 years apart.
AB  - What is already known about this subject Factors associated with children's body
      mass index (BMI) include parents' BMIs, birth weight, maternal smoking, sleep
      duration and television watching. Few studies have attempted to quantify either
      changes in the association between risk factors and BMI or the contribution of
      changes in the risk factors to increases in BMI over a generation. What this
      study adds The magnitude of the association between most risk factors and
      children's BMIs has not changed over a 29-year period. Increases in the
      population level of mothers' body mass index (BMI) explains ~20% of the increase
      in children's BMI whereas the smaller increase in fathers' BMI contributes only
      6%. Maternal smoking, despite the decrease in prevalence, contributes ~17%.
      OBJECTIVE: Using two cohorts born 29 years apart in Dunedin, New Zealand we aim
      to examine changes in risk factors and their associations with body mass index
      (BMI) at ages 3 and 7 years, and estimate their contribution to the secular
      changes in BMI at age 7 years. METHODS: Birth weight and anthropometric measures
      at ages 3, 5 and 7 years were obtained for 974 participants in the Dunedin
      Multidisciplinary Health and Development Study (DMHDS), born in 1972-1973, and
      241 in the Family Lifestyle, Activity, Movement and Eating Study (FLAME), born in
      2001-2002. Information about maternal age, education and smoking in pregnancy, as
      well as breastfeeding, children's television time and time in bed, was obtained
      by questionnaire. RESULTS: The increase in BMI over the 29-year period was 0.84
      (95% CI 0.61, 1.06) kg m(-2) at age 7. A 1-unit difference in the mother's BMI
      was associated with a 0.06 (0.03, 0.08) kg m(-2) difference in offspring in both
      studies; the 3.4 (2.8, 4.0) kg m(-2) increase in the mothers' BMIs accounts for a
      change of 0.19 kg m(-2) in the children's BMI. The much smaller generational
      increase in fathers' BMI (0.7 kg m(-2) ) correspondingly had a more limited
      effect on change in child BMI over time (0.06 kg m(-2) ). Although smoking in
      pregnancy decreased by 15% (8, 21) its association with BMI increased from 0.20 (
      0.01, 0.42) in the DMHDS cohort to 1.24 (0.76, 1.71) kg m(-2) in the FLAME
      cohort, contributing 0.18 kg m(-2) to the increase in children's BMI.
      CONCLUSIONS: Societal factors such as higher maternal BMI and smoking in
      pregnancy contribute most to the secular increase in BMI, with changes in
      behavioural factors, including sleep and television viewing, having little effect
      in this setting.

PMID- 23001952
TI  - Investigation of gold fluorides and noble gas complexes by matrix-isolation
      spectroscopy and quantum-chemical calculations.
AB  - Noble with a difference: Matrix-isolation experiments and quantum-chemical
      calculations have led to the characterization of two new compounds, namely first
      open-shell binary gold fluoride, AuF(2), and a NeAuF complex. Moreover, ArAuF,
      AuF(3), Au(2)F(6), and monomeric AuF(5) have been produced and identified under
      cryogenic conditions in neon and argon matrices.

PMID- 23001953
TI  - Body size and metabolic differences in Maine Coon cats with and without
      hypertrophic cardiomyopathy.
AB  - An interplay between growth, glucose regulation and hypertrophic cardiomyopathy
      (HCM) may exist, but has not been studied in detail. The purpose of this study
      was to characterize morphometric features, insulin-like growth factor-1 (IGF-1)
      and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition
      score (BCS), head length and width, and abdominal circumference were measured in
      Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for
      measurement of humerus length, and fourth and twelfth vertebrae length) were also
      performed. Blood was collected for biochemistry profile, DNA testing, insulin and
      IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and
      MYBPC-, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and
      MYBPC-, n = 30). There were no significant differences in any measured parameter
      between MYBPC+ and MYBPC- cats. Cats with HCM were significantly older (P
      <0.001), heavier (P = 0.006), more obese (P = 0.008), and had longer humeri (P =
      0.02) compared with the HCM- group. Cats with HCM also had higher serum glucose
      (P = 0.01), homeostasis model assessment (HOMA) and IGF-1 (P = 0.01)
      concentrations, were from smaller litters (P = 0.04), and were larger at 6 months
      (P = 0.02) and at 1 year of age (P = 0.03). Multivariate analysis revealed that
      age (P <0.001), BCS (P = 0.03) and HOMA (P = 0.047) remained significantly
      associated with HCM. These results support the hypothesis that early growth and
      nutrition, larger body size and obesity may be environmental modifiers of genetic
      predisposition to HCM. Further studies are warranted to evaluate the effects of
      early nutrition on the phenotypic expression of HCM.

PMID- 23001954
TI  - Simultaneous screening and determination of 18 illegal adulterants in herbal
      medicines and health foods for male sexual potency by ultra-fast liquid
      chromatography-electrospray ionization tandem mass spectrometry.
AB  - An ultra-fast liquid chromatography-electrospray ionization tandem mass
      spectrometry method was developed and validated to simultaneously screen,
      confirm, and determine 18 illegal adulterants in herbal medicines and health
      foods for male sexual potency. The separation was achieved on a Shim-Pack XR-ODS
      II column (2.0 * 100 mm, 2.2 MUm) with acetonitrile and aqueous solution (12
      mmol/L ammonium formate, 0.01% acetic acid) as mobile phase at a flow rate of 0.4
      mL/min with a gradient elution. The column temperature was maintained at 40
      degrees C and the run time was within 18 min. The 18 illegal adulterants were
      detected in electrospray ionization positive mode by multiple-reaction
      monitoring. All the calibration curves showed good linearity with correlation
      coefficient (r) higher than 0.996 within the tested concentration ranges. The
      extraction recoveries and relative recoveries were in the range of 79.5-114% and
      82.0-120%, respectively. The RSD of repeatability and intermediate precision was
      all less than 18% and the accuracy was in the range of 81.7-118%. The intra-day
      and inter-day stability was in the range of 86.8-110%. The validated method was
      successfully applied to screen, confirm, and determine 16 samples. Nine products
      were confirmed to contain illegal adulterants and the contents of adulterants
      were related to the therapeutic dosages.

PMID- 23001955
TI  - The influence of switching from haloperidol decanoate depot to risperidone long
      acting injection on the clinical symptoms and cognitive function in
      schizophrenia.
AB  - OBJECTIVE: This study was a comparative investigation of the effects on clinical
      symptoms and cognitive function of switching the treatment of schizophrenia
      patients from haloperidol decanoate depot to risperidone long-acting injection
      (RLAI) compared with a control group that continued receiving haloperidol
      decanoate depot. METHODS: This study was a 24-week, non-randomized, non-double
      blind, open-label trial. The subjects' clinical symptoms were assessed using the
      Positive and Negative Syndrome Scale, and their cognitive function was assessed
      using the Wisconsin Card Sorting Test: Keio Version to assess executive function
      and the St. Marianna University School of Medicine's Computerized Memory Test to
      assess memory and concentration at 0 and 24 weeks. RESULTS: The mean change from
      baseline in the number of categories achieved at the second stage of the
      Wisconsin Card Sorting Test: Keio Version was significantly greater in the RLAI
      group than in the control group. The mean changes from baseline in the individual
      St. Marianna University School of Medicine's Computerized Memory Tests were
      significantly greater in the RLAI group than in the control group. The RLAI group
      needed a lower dosage of biperiden compared with the control group, even though
      they had similar risperidone-equivalent daily dosages. CONCLUSION: The results of
      this study suggest the possibility that switching from haloperidol decanoate
      depot to RLAI may improve cognitive function including memory, executive
      function, motor processing function, and attention.

PMID- 23001957
TI  - Stimulation of bioluminescence in Noctiluca sp. using controlled temperature
      changes.
AB  - Bioluminescence induced by multifarious stimuli has long been observed and is
      remains under investigation because of its great complexity. In particular, the
      exact mechanism underlying bioluminescence is not yet fully understood. This work
      presents a new experimental method for studying Noctiluca sp. bioluminescence
      under temperature change stimulation. It is a study of Noctiluca sp.
      bioluminescence using controlled temperature changes in a tank. A characteristic
      of this experiment is the large volume of water used (1 m(3) in a tank of 2 * 1 *
      1 m). Temperature changes were controlled by two methods. In the first, a flask
      filled with hot water was introduced into the tank and in the second, a water
      heater was used in the tank. Temperature changes were recorded using sensors.
      Noctiluca sp. bioluminescence was recorded using a Canon 5D Mark II and this
      allowed the characteristics of Noctiluca sp. bioluminescence under temperature
      change stimulation to be monitored.

PMID- 23001956
TI  - Dexamethasone promotes tolerance in vivo by enriching CD11clo CD40lo tolerogenic
      macrophages.
AB  - We previously showed that antigen immunization in the presence of the
      immunosuppressant dexamethasone (a strategy we termed "suppressed immunization")
      could tolerize established recall responses of T cells. However, the mechanism by
      which dexamethasone acts as a tolerogenic adjuvant has remained unclear. In the
      present study, we show that dexamethasone enriches CD11c(lo) CD40(lo) 
      macrophages in a dose-dependent manner in the spleen and peripheral lymph nodes
      of mice by depleting all other CD11c(+) CD40(+)  cells including dendritic cells.
      The enriched macrophages display a distinct MHC class II (MHC II)(lo) CD86(hi) 
      phenotype. Upon activation by antigen in vivo, CD11c(lo) CD40(lo)  macrophages
      upregulate IL-10, a classic marker for tolerogenic antigen-presenting cells, and
      elicit a serum IL-10 response. When presenting antigen in vivo, these cells do
      not elicit recall responses from memory T cells, but rather stimulate the
      expansion of antigen-specific regulatory T cells. Moreover, the depletion of
      CD11c(lo) CD40(lo)  macrophages during suppressed immunization diminishes the
      tolerogenic efficacy of the treatment. These results indicate that dexamethasone
      acts as a tolerogenic adjuvant partly by enriching the CD11c(lo) CD40(lo) 
      tolerogenic macrophages.

PMID- 23001958
TI  - Angiotensin-converting enzyme (ACE)-inhibitory activity of boza, a traditional
      fermented beverage.
AB  - BACKGROUND: In this study the angiotensin-converting enzyme (ACE)-inhibitory
      activity of boza and protein fractions of boza separated according to molecular
      weight was determined. In addition, the effect of in vitro digestion on ACE
      inhibitory activity was investigated. RESULTS: The protein content, ACE
      inhibitory activity and IC(50) value of boza were 1.0896 +/- 0.08%, 76.76 +/-
      14.93% and 7.2 +/- 0.28 ug protein mL(-1) respectively. The protein hydrolysate
      was separated into three fractions according to molecular weight (MW), i.e. MW <
      5000 Da, 5000 < MW < 10 000 Da and 10 000 < MW < 20 000 Da. The lowest IC(50)
      value (0.268 +/- 0.07 ug protein mL(-1)) was found for the fraction with 5000 <
      MW < 10 000 Da (P < 0.05). After in vitro digestion the ACE-inhibitory activities
      of stomach and intestine dialysates were almost the same (P > 0.05). The IC(50)
      value of stomach digest was determined as 2.06 +/- 0.32 (ug protein mL(-1)).
      However, the IC(50) value of intestine digest could not be determined, because
      all dialysates with different protein concentrations displayed ACE-inhibitory
      activity greater than 50%. CONCLUSION: The findings indicate that boza, protein
      hydrolysate, fractionated hydrolysates and dialysates obtained after in vitro
      digestion contain bioactive compounds with different ACE-inhibitory activities.
      Based on these results, boza can be considered as a good source of ACE-inhibitory
      peptides.

PMID- 23001959
TI  - Dispersal of marine organisms and the grand challenges in biology: an
      introduction to the symposium.
AB  - Understanding dispersal and its complex variables is critical to understanding
      the ecology and evolution of life histories of species, but research on dispersal
      tends to reflect or emphasize particular disciplines, such as population
      genetics, functional morphology, evolutionary and developmental biology,
      physiology, and biophysics, or to emphasize a particular clade or functional
      group (e.g., fish, planktotrophs or lecithotrophs, pelagic or benthic organisms)
      in marine ecosystems. The symposium on "Dispersal of Marine Organisms" assembled
      an interdisciplinary group of outstanding young and established speakers to
      address dispersal in marine organisms in order to foster integration and cross
      talk among different disciplines and to identify gaps in our knowledge and
      suggest areas for future research.

PMID- 23001960
TI  - Optical design of transparent thin metal electrodes to enhance in-coupling and
      trapping of light in flexible polymer solar cells.
AB  - ITO-free polymer solar cells with efficiencies as high as 6.6% and 5.8% are
      fabricated on glass and polyethylene naphthalate (PEN) by using TeO(2) to enhance
      the in-coupling of light in an Ag-Ag microcavity. These cells exhibit higher
      performance, selective microcavity resonance as a function of the thickness of
      TeO(2) , and better bending stability than flexible devices made with ITO.

PMID- 23001961
TI  - Genetic analysis of sexual dimorphism of body weight in broilers.
AB  - Variation in sexual dimorphism (SD) is particularly marked in meat-type chickens.
      This paper investigates the genetic basis of SD in an important economic trait,
      i.e. body weight (BW) at 35 days of age, in broilers by applying quantitative
      genetic analysis. A large dataset comprising 203,323 BW records of a commercial
      line of broiler chicken was used. First, a bivariate approach was employed
      treating BW as a sex-specific trait. During this approach, seven bivariate models
      were applied and variances due to direct additive genetic, maternal genetic and
      maternal environmental effects were estimated via the restricted maximum
      likelihood method. The best-fitting model included direct additive genetic,
      maternal genetic and maternal environmental effects with a direct-maternal
      genetic covariance. Differences between male and female direct heritabilities
      were non-significant (0.28 vs. 0.29 for males and females, respectively),
      implying no need for sex-specific selection strategies. The direct-maternal
      genetic correlation was more strongly negative in males than in females (-0.72
      vs. -0.56), implying a more profound antagonism between direct additive and
      maternal genetic effects in this particular gender. The direct genetic
      correlation of BW between the two sexes was as high as 0.91, i.e. only slightly
      lower than unity. Second, variance components and genetic parameters of two
      measures of SD, i.e. the weight difference (Delta) and the weight ratio (R),
      between the genders were estimated. Direct heritabilities for both measures were
      significantly different to 0 but of low magnitude (0.04). Apart from the additive
      maternal covariance, no other random effects were found to be of importance for
      Delta and R. The results of the present study suggest that only minimal selection
      responses due to the selection of Delta and/or R and a small capacity for
      amplifying or reducing the BW differences between the sexes are to be expected in
      this specific population. Furthermore, selection pressure on BW is expected to
      amplify SD.

PMID- 23001962
TI  - Bridging environmental mixtures and toxic effects.
AB  - Biological Response Indicator Devices Gauging Environmental Stressors (BRIDGES)
      is a bioanalytical tool that combines passive sampling with the embryonic
      zebrafish developmental toxicity bioassay to provide a quantitative measure of
      the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs),
      which sequester and concentrate bioavailable organic contaminants from the
      environment, were deployed in the Willamette and Columbia Rivers within and
      outside of the Portland Harbor Superfund site in Portland, OR, USA. Six sampling
      events were conducted in the summer and fall of 2009 and 2010. Passive sampling
      device extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds
      and screened for 1,201 chemicals of concern using deconvolution-reporting
      software. The developmental toxicity of the extracts was analyzed using the
      embryonic zebrafish bioassay. The BRIDGES tool provided site-specific, temporally
      resolved information about environmental contaminant mixtures and their toxicity.
      Multivariate modeling approaches were applied to paired chemical and toxic
      effects data sets to help unravel chemistry-toxicity associations. Modeling
      elucidated spatial and temporal trends in PAH concentrations and the toxicity of
      the samples and identified a subset of PAH analytes that were the most highly
      correlated with observed toxicity. Although the present study highlights the
      complexity of discerning specific bioactive compounds in complex mixtures, it
      demonstrates methods for associating toxic effects with chemical characteristics
      of environmental samples.

PMID- 23001963
TI  - Is Ginkgo biloba a cognitive enhancer in healthy individuals? A meta-analysis.
AB  - OBJECTIVE: We conducted a meta-analysis to examine whether Ginkgo biloba (G.
      biloba) enhances cognitive function in healthy individuals. METHODS: Scopus,
      Medline, Google Scholar databases and recent qualitative reviews were searched
      for studies examining the effects of G. biloba on cognitive function in healthy
      individuals. We identified randomised controlled trials containing data on memory
      (K = 13), executive function (K = 7) and attention (K = 8) from which effect
      sizes could be derived. The analyses provided measures of memory, executive
      function and attention in 1132, 534 and 910 participants, respectively. RESULTS:
      Effect sizes were non-significant and close to zero for memory (d = -0.04: 95%CI 
      0.17 to 0.07), executive function (d = -0.05: 95%CI -0.17 to 0.05) and attention
      (d = -0.08: 95%CI -0.21 to 0.02). Meta-regressions showed that effect sizes were
      not related to participant age, duration of the trial, daily dose, total dose or
      sample size. CONCLUSIONS: We report that G. biloba had no ascertainable positive
      effects on a range of targeted cognitive functions in healthy individuals.

PMID- 23001964
TI  - The potential role of fatty liver in paediatric metabolic syndrome: a distinct
      phenotype with high metabolic risk?
AB  - BACKGROUND: The prevalence of obesity and its metabolic consequences has
      dramatically increased in the last two decades urging physicians to find a
      reliable definition for early detection, treatment and possibly prevention of
      metabolic syndrome (MS). MS could be diagnosed in adult patients in the presence
      of a large waist circumference and >=2 of the following features: high serum
      triglycerides, low serum high-density lipoprotein cholesterol, high blood
      pressure and high fasting glucose. The definition of MS in children is more
      problematic, and the potential role of its single components on metabolic risk
      remains largely undefined. Recent evidence strongly suggests not only a
      relationship between non-alcoholic fatty liver disease (NAFLD) and MS in obese
      children, adolescents and adults, but also the key role exerted by liver fat
      deposition in the pathogenesis of MS. CONCLUSION: We propose that NAFLD should be
      routinely checked in obese subjects because early lifestyle changes may be
      effective in reducing the overall risk of MS.

PMID- 23001965
TI  - Chemotherapy control by breath profile with application of SPME-GC/MS method.
AB  - Chemotherapy used as a treatment against lung cancer has influence on metabolic
      processes occurring in healthy cells. The changes of biochemical pathways
      proceeded inside cells might be observed in expired air. In the experiment,
      breath analysis was carried out before and after anticancer therapy. Expired air
      samples were collected from 22 patients with a biopsy confirmed lung cancer.
      Volatile organic compounds present in breath were analyzed by gas
      chromatography/mass spectrometry. For enrichment of analytes solid-phase
      microextraction technique was applied. Eight fibers covered by different sorbents
      were tested. Carboxen-polydimethylsiloxane fiber revealed the highest extraction
      efficiency in relation to analytes in breath. The data showed that cytostatic
      drugs increase the concentration of acetone and isoprene in the breath collected
      after chemotherapy. Volatile metabolites of administrated drugs were not
      identified in expired air.

PMID- 23001966
TI  - Structural differences between thermophilic and mesophilic membrane proteins.
AB  - The evolutionary adaptations of thermophilic water-soluble proteins required for
      maintaining stability at high temperature have been extensively investigated.
      Little is known about the adaptations in membrane proteins, however. Here, we
      compare many properties of mesophilic and thermophilic membrane protein
      structures, including side-chain burial, packing, hydrogen bonding, transmembrane
      kinks, loop lengths, hydrophobicity, and other sequence features. Most of these
      properties are quite similar between mesophiles and thermophiles although we
      observe a slight increase in side-chain burial and possibly a slight decrease in
      the frequency of transmembrane kinks in thermophilic membrane protein structures.
      The most striking difference is the increased hydrophobicity of thermophilic
      transmembrane helices, possibly reflecting more stringent hydrophobicity
      requirements for membrane partitioning at high temperature. In agreement with
      prior work examining transmembrane sequences, we find that thermophiles have an
      increase in small residues (Gly, Ala, Ser, and Val) and a strong suppression of
      Cys. We also find a relative dearth of most strongly polar residues (Asp, Asn,
      Glu, Gln, and Arg). These results suggest that in thermophiles, there is
      significant evolutionary pressure to offload destabilizing polar amino acids, to
      decrease the entropy cost of side chain burial, and to eliminate thermally
      sensitive amino acids.

PMID- 23001967
TI  - Darwin shines light on the evolution of bioluminescence.

PMID- 23001968
TI  - Photocontrol over cooperative porphyrin self-assembly with phenylazopyridine
      ligands.
AB  - The cooperative self-assembly of chiral zinc porphyrins is regulated by a
      photoresponsive phenylazopyridine ligand. Porphyrin stacks depolymerize into
      dimers upon axial ligation and the strength of the coordination is regulated by
      its photoinduced isomerization, which shows more than 95 % conversion ratio for
      both photostationary states.

PMID- 23001969
TI  - Improved charge transport and absorption coefficient in indacenodithieno[3,2
      b]thiophene-based ladder-type polymer leading to highly efficient polymer solar
      cells.
AB  - A novel ladder-type donor (IDTT) is developed by substituting the two outward
      thiophenes of the IDT donor with two thieno[3,2-b]thiophenes. The polymer derived
      from this donor possesses longer effective conjugation and better planarity,
      which improves electron delocalization along the polymer backbone and charge
      mobility. The polymer solar cell device using PIDTT-DFBT shows a high power
      conversion efficiency of 7.03% with a large open-circuit voltage of 0.95 V
      without using any additives or post-solvent/thermal annealing processes.

PMID- 23001970
TI  - Enhanced nebulization efficiency of electrospray mass spectrometry: improved
      sensitivity and detection limit.
AB  - A novel electrospray nebulizer has been designed, which includes an additional
      nebulization gas capillary inside the liquid capillary. This design offers
      significantly enhanced ionization efficiency compared with the classic nebulizer
      design and leads to improved sensitivity (by three to 10 times) and decreases the
      detection limit, on an average 10 times. We see these results as the first step
      in the design of ESI nebulizers offering improved sensitivity and higher
      robustness. Possible future developments would include optimization of the
      dimensions of the capillaries as well as testing the nebulizer for other matrices
      and analytes.

PMID- 23001971
TI  - Relationships between physiological indicators in blood, and their yield, as well
      as chemical composition of milk obtained from organic dairy cows.
AB  - BACKGROUND: The occurrence of metabolic overload in cows maintained in organic
      herds is very likely, because organic production promotes feeding with high
      roughage diets and discourages supplementation with concentrates supplementation.
      It has the potential to negatively affect milk quality. The aim of this study was
      to determine the influence of physiological indicators in blood, reflecting the
      energy metabolism and liver status of dairy cows kept in organic herds, on the
      content of bioactive components in milk and the influence of lactation stage and
      feeding season on changes in milk components. RESULTS: A significant positive
      correlation was found between beta-hydroxybutyric acid and the daily milk yield
      of lactating cows. beta-Hydroxybutyric acid was negatively correlated with
      lactation phase and polyunsaturated fatty acids as well as saturated fatty acids
      content in milk. A significant negative correlation was observed between average
      daily milk yield and alanine aminotransferase concentration in blood. A low level
      of production in organic farms had a positive impact on the content of conjugated
      linoleic acid (20% increase), vitamin A (21% increase) and vitamin E (11%
      increase). CONCLUSION: The study has shown significant correlations between
      metabolic profiles and milk yields, as well as milk composition. In addition,
      there is evidence that the intensity of the production system significantly
      influences the metabolic profile and chemical composition of cow's milk. It could
      even be concluded that the ecological system affects not only the quality of
      milk, but also the health of cows.

PMID- 23001972
TI  - Channeling drug discovery.

PMID- 23001975
TI  - Association of genetic variations in X-ray repair cross-complementing group 1 and
      Tourette syndrome.
AB  - BACKGROUND: X-ray repair cross-complementing group 1 (XRCC1) plays a central role
      in mammalian DNA repair process. The polymorphism rs25487 (Arg>Gln at codon 399)
      of this gene is common in Han Chinese population. OBJECTIVES: The objective of
      this study was to analyze the association between this functional SNP of XRCC1
      and Tourette syndrome (TS) in Han Taiwan Chinese population. METHODS: Genotyping
      was performed by using PCR-RFLP method on 73 TS patients and 158 normal controls.
      RESULTS: Our data indicated that genotype frequency of A/G polymorphism at codon
      399 of the patients differed from the controls (P = 0.026, OR: 2.22, 95% CI: 1.22
      4.03). The allele frequency analysis also showed significant differences with
      higher A allele frequency in patients (P = 0.015, OR: 1.70, 95% CI: 1.11-2.62).
      CONCLUSION: Our study indicates that the functional SNP at codon 399 of XRCC1 is
      associated with TS development.

PMID- 23001976
TI  - Mycobacterium wolinskyi infection confirmed by rpoB gene sequencing.
AB  - Identification of rapidly growing mycobacteria (RGM) is problematic because there
      are many taxonomic changes. 16S rRNA gene is commonly used to identify
      Mycobacterium species, but alternative gene targets have been introduced for more
      accurate identification. We report a rare case of a prosthetic knee infection due
      to Mycobacterium wolinskyi. The isolate was not identified by 16S rRNA gene
      sequencing alone and substantially confirmed by rpoB gene sequencing. The
      identification was delayed because our laboratory did not routinely identify RGM
      to the species level. Simultaneous sequencing of both 16S rRNA and rpoB genes
      will allow rapid and accurate identification of M. wolinskyi isolates.

PMID- 23001977
TI  - Development of a bioassay system for human growth hormone determination with
      close correlation to immunoassay.
AB  - Serum growth hormone (GH) level is measured largely through immunoassays in
      clinical practice. However, a few cases with bioinactive and immunoreactive GH
      have also been reported. We describe here a new bioassay system for GH
      determination using the BaF/GM cell line, which proliferates in a dose-dependent
      manner on hGH addition; cell proliferation was blocked by anti-hGH antibody. This
      bioassay had the lowest detection limit (~0.02 ng/ml) reported thus far and the
      highest specificity for GH. The bioassay results were compared with those of an
      immunoradiometric assay across 163 patient samples in various endocrine states. A
      close correlation (the ratio of bioactivity/immunoreactivity was 1.04 +/- 0.33,
      mean +/- SD) was observed between bioactivity and immunoreactivity in these
      samples. The newly developed system is a specific, sensitive, easy, and fast
      bioassay system for GH determination; we consider it useful for evaluating GH
      bioactivity in various endocrine states.

PMID- 23001978
TI  - Relationship of fat distribution with adipokines in patients with acquired
      immunodeficiency virus infection.
AB  - BACKGROUND: The aim was to examine the relationship of fat distributions with
      adipokines concentrations in HIV-infected patients. METHODS: This was a cross
      sectional analysis of 36 HIV (free of lipodystrophy) infected patients. Dual
      energy X-ray absorptiometry was used. RESULTS: In the multivariate analysis,
      basal adiponectin concentration was a dependent variable, whereas waist to hip
      ratio and abdominal fat mass were independent predictors in the model (F = 5.1; P
      < 0.05). Adiponectin concentration decreases by 5.541.2 MUg/ml (CI 95%: 8,071.9
      3,029.1) for each unit of waist to hip ratio and 561.9 ng/ml (CI 95%: 918.2
      213.4) for each kilogram of fat mass of abdominal area. In the multivariate
      analysis, basal leptin concentration was a dependent variable, whereas waist
      circumference remained an independent predictor in the model (F = 6.3; P < 0.05),
      with a direct correlation. Leptin concentration increases by 0.067 ng/ml (CI 95%:
      0.001-0.12) for each centimeter of waist circumference. CONCLUSIONS: Leptin and
      adiponectin are related with adiposity in HIV-infected patients.

PMID- 23001979
TI  - Clinical relevance of antibodies to cardiolipin in patients with chronic
      hepatitis C.
AB  - The significance of antibodies to cardiolipin (anti-CL) remains uncertain in
      patients with chronic hepatitis C (CH-C). The main purpose of this study was to
      elucidate the clinical characteristics of patients with CH-C seropositive for
      anti-CL. The prevalence of anti-CL and clinical parameters associated with anti
      CL in those patients were examined. Six of the 45 (13%) patients with CH-C had
      anti-CL. However, none of these six CH-C patients fulfilled the criteria for
      antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels
      in CH-C patients with anti-CL were significantly higher than those in CH-C
      patients without anti-CL. Serum triglyceride levels positively correlated with
      serum ApoB levels. CH-C patients with anti-CL had significantly more progressive
      hepatic fibrosis than those without anti-CL. The degree of 8-hydroxy 2'
      deoxyguanosine (8-OHdG) expression in the liver tissue was more severe in CH-C
      patients with anti-CL than in those without it. However, the emergence of anti-CL
      in CH-C patients was independent of insulin resistance, hepatic steatosis, and
      iron overload. These findings suggest that the emergence of anti-CL is associated
      with oxidative stress and that CH-C patients seropositive for anti-CL have
      clinical characteristics of hypertriglyceridemia, which derives from the
      facilitation of ApoB synthesis, and progressive hepatic fibrosis.

PMID- 23001980
TI  - A simple, rapid atmospheric pressure chemical ionization liquid chromatography
      tandem mass spectrometry method for the determination of 25-hydroxyvitamin D2 and
      D3.
AB  - Vitamin D plays a vital role not only in bone health but also in pathophysiology
      of many other body functions. In recent years, there has been significant
      increase in testing of 25-hydroxyvitamin D (25-OH vitamin D), a marker of vitamin
      D deficiency. The most commonly used methods for the measurement of 25-OH vitamin
      D are immunoassays and liquid chromatography tandem mass spectrometry (LC-MS-MS).
      Since immunoassays suffer from inaccuracies and interferences, LC-MS-MS is a
      preferred method. In LC-MS-MS methods, 25-OH vitamin D is extracted from serum or
      plasma by solid-phase or liquid-phase extraction. Because these extraction
      methods are time consuming, we developed an easy method that uses simple protein
      precipitation followed by injection of the supernatant to LC-MS-MS. Several mass
      to-charge (m/z) ratio transitions, including commonly used transitions based on
      water loss, were evaluated and several tube types were tested. The optimal
      transitions for 25-OH vitamin D2 and D3 were 395.5 > 269.5 and 383.4 > 257.3,
      respectively. The reportable range of the method was 1-100 ng/mL, and
      repeatability (within-run) and within-laboratory imprecision were <4% and <6%,
      respectively. The method agreed well with the solid-phase extraction methods.

PMID- 23001981
TI  - Measurement of urinary cystatin C with a particle-enhanced turbidimetric
      immunoassay on Architect ci8200.
AB  - BACKGROUND: Cystatin C is a low-molecular-weight protein that is freely filtered
      by the glomerulus and catabolized after reabsorption by the proximal tubular
      cells in healthy subjects. Urinary cystatin C is a potential biomarker for
      tubular damage including acute kidney injury (AKI) in the acute phase when
      patients are submitted to the intensive care unit. METHODS: The aim of this study
      was to perform a method validation of urinary analysis of cystatin C by particle
      enhanced turbidimetric immunoassay (PETIA) on a high-throughput chemical
      analyzer. Total assay time was 10 min. The antigen excess, linearity, lower limit
      of quantification (LoQ), recovery, assay precision, stability, and interference
      caused by hemoglobin were evaluated. RESULTS: The LoQ was calculated to 0.020
      mg/l with a coefficient of variation (CV) <= 10%. No hook effect was observed and
      the assay was linear over the studied interval less than 0.020-0.950 mg/l with a
      regression of R2 = 0.9994. The assay had a recovery between 93-100% and the assay
      precision had a total CV of less than 3.5%. Cystatin C was stable for 3 days in
      room temperature and 14 days in +4C. The assay did not show any major
      interference with hemoglobin at a hemoglobin concentration of 10 g/L. The
      reference interval for urine cystatin C was less than 0.166 mg/l. CONCLUSION: The
      urinary cystatin C PETIA showed good precision and performance characteristics
      including short test turnaround times that are necessary qualifications for a
      biomarker at a routine laboratory.

PMID- 23001982
TI  - Alterations of dendritic cell subsets and TH1/TH2 cytokines in the peripheral
      circulation of patients with superficial transitional cell carcinoma of the
      bladder.
AB  - BACKGROUND: Dendritic cells (DCs) and cytokines play an important role in the
      tumor growth and recurrence. METHODS: Sixty-six patients with superficial
      transitional cell carcinoma of the bladder (STCCB) and 38 healthy controls were
      studied to investigate the percentages of DC subsets, monocyte-derived DC (MoDC)
      function, and alterations of Th1 and Th2 cytokines. MoDCs were generated and
      three-color flow cytometry was used for determining the phenotype of MoDCs and DC
      subsets. The ability to stimulate autologous T cells was tested in mixed
      leukocyte reaction (MLR). The levels of various cytokines were measured using
      commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit.
      RESULTS: The myeloid DC (mDC) counts, MoDC surface molecular expression, and
      stimulatory capacity to T cells were impaired in STCCB patients than in controls.
      The percentage of mDC and the expression of CD80, CD83, and CD86 were lower in
      patients showing recurrence. The serum levels of IL-2 and IFN-gamma were found to
      be significantly lower while IL-4, IL-6, and IL-10 were significantly higher in
      STCCB patients than in controls. IL-6 was found to be significantly higher in
      recurrent patients. CONCLUSION: The impairment of mDC counts and MoDC function
      with imbalance of Th1/Th2 cytokines was closely associated with proliferation and
      recurrence of STCCB.

PMID- 23001983
TI  - Stability of electrolyte determinations on the Siemens Advia 1800 analyzer.
AB  - BACKGROUND: It is sometimes necessary for the laboratory to re-test samples for
      critical serum electrolyte levels. It is important to assure reproducibility of
      results when testing is performed on stored, refrigerated samples. We have tested
      the reproducibility of results for the critical electrolytes, Na, K, Cl and Ca,
      from ten randomly selected patients'sera over our maximum storage period of nine
      (9) days on the Siemens Advia 1800 analyzer. The ranges for each electrolyte were
      131-150 meq/L (Na), 3.4-5.2 meq/L (K), 101-123 meq/L (Cl) and 7.3-9.9 mg/dL (Ca).
      METHODS: We used ion-selective electrodes for Na, K and Cl and the ortho
      cresolphthalein dye method for Ca. RESULTS: We find that the reproducibility of
      determinations for all of these electrolytes was excellent, i.e. the coefficients
      of variation for each electrolyte determination for each patient were low.
      CONCLUSION: The methods of measurement for these electrolytes on the Advia 1800
      are reliable and reproducible.

PMID- 23001984
TI  - Routine determination of GFR in renal transplant recipients by HPLC
      quantification of plasma iohexol concentrations and comparison with estimated
      GFR.
AB  - Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable
      in renal transplant recipients (RTR) and should be replaced by iohexol plasma
      clearance measurement. However, this method has poor availability in health
      centers. The aim of our study was to develop a high-performance liquid
      chromatography (HPLC) method for plasma iohexol measurement in routine practice
      and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC
      method using UV detection. We evaluated sample storage conditions to provide
      recommendations for routine practice. Then, we compared GFRbased on plasma
      iohexol clearance (GFR-iohexol) to eGFR using modification of diet in renal
      disease, Cockcroft and Gault, and CDK-EPIequations in 40 RTR. The method was
      validated over a concentration range of 15-300 MUg/l. Excellent linearity (r >
      0.998), inter- and intraday precision (CV < 3.3%), and accuracy (>96.8%) were
      complied with ICH guidelines. We also demonstrated excellent samples stability (9
      days). Although eGFR methods are not references in RTR, we found a correct
      concordance between eGFR and GFR-iohexol in our population. To conclude, our
      method is simple, rapid, accurate, and reliable for routine clinical and research
      use especially in RTR.

PMID- 23001985
TI  - External evaluation of the Dimension Vista 1500(r) intelligent lab system.
AB  - BACKGROUND: Dimension Vista(r) analyzer combines four technologies (photometry,
      nephelometry, V-LYTE(r) integrated multisensor potentiometry, and LOCI(r)
      chemiluminescence) into one high-throughput system. METHODS: We assessed
      analytical performance of assays routinely performed in our emergency laboratory
      according to the VALTEC protocol, and practicability. RESULTS: Precision was good
      for most parameters. Analytical domain was large and suitable for undiluted
      analysis in most clinical settings encountered in our hospital. Data were
      comparable and correlated to our routine analyzers (Roche Modular DP(r), Abbott
      AXSYM(r), Siemens Dimension(r) RxL, and BN ProSpec(r)). Performance of
      nephelometric and LOCI modules was excellent. Functional sensitivity of high
      sensitivity C-reactive protein and cardiac troponin I were 0.165 mg/l and 0.03
      ng/ml, respectively (coefficient of variation; CV < 10%). The influence of
      interfering substances (i.e., hemoglobin, bilirubin, or lipids) was moderate, and
      Dimension Vista(r) specifically alerted for interference according to HIL
      (hemolysis, icterus, lipemia) indices. Good instrument performance and full
      functionality (no reagent or sample carryover in the conditions evaluated,
      effective sample-volume detection, and clot detection) were confirmed. Simulated
      routine testing demonstrated excellent practicability, throughput, ease of use of
      software and security. CONCLUSION: Performance and practicability of Dimension
      Vista(r) are highly suitable for both routine and emergency use. Since no volume
      detection and thus no warning is available on limited sample racks, pediatric
      samples require special caution to the Siemens protocol to be analyzed in secured
      conditions. Our experience in routine practice is also discussed, i.e., the
      impact of daily workload, "manual" steps resulting from dilutions and pediatric
      samples, maintenances, flex hydration on instrument's performance on throughput
      and turnaround time.

PMID- 23001986
TI  - Relation of leptin and adiponectin with cardiovascular risk factors, intact
      parathormone, and vitamin D levels in patients with primary hyperparathyroidism.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with high
      cardiovascular morbidity. The aim of the present study was to explore the
      relationship of leptin and adiponectin levels with cardiovascular risk factors
      and anthropometric parameters in patients with PHTP with and without metabolic
      syndrome (MS). METHODS: A total of 62 patients with PHPT were enrolled. Weight,
      blood pressure, basal glucose, insulin, total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides,
      insulin, HOMA-R, intact parathormone, vitamin D, calcium, leptin, and adiponectin
      levels were measured in fasting condition. RESULTS: Prevalence of MS with ATP III
      definition was 32.3% (20 patients; 15 females (75%) and 5 males (25%)) and 67.7%
      patients without MS (n = 42 patients; 35 females (83.3%) and 7 males (16.7%)). In
      the analysis with leptin as dependent variable, the weight and HOMA-R levels
      remained in the model (F = 9.2; P < 0.05), with an increase of 1.31 (CI 95%: 0.24
      2.31) ng/ml with each one unit of HOMA-R and an increase of 0.4 (CI 95%: 0.01
      0.84) ng/ml with each 1 kg of weight. In a second model with adiponectin as
      dependent variable, the HOMA-R and HDL-cholesterol levels remained in the model
      (F = 7.37; P < 0.05), with a decrease of -0.62 (CI 95%: 0.01-1.1) ng/ml with each
      one point of HOMA-R and an increase of 0.18 (CI 95%: 0.04-0.38) ng/ml with each 1
      mg/dl of HDL-cholesterol. In the multivariate, PTH I was not associated with
      other variables. CONCLUSION: There was a high prevalence of MS-32.3% of patients
      with PHPT presented an MS. Serum levels of leptin and adiponectin are not related
      with PTH I, vitamin D, and calcium levels in patients with PHPT.

PMID- 23001987
TI  - Increased MPV is not a significant predictor for preeclampsia during pregnancy.
AB  - BACKGROUND: Preeclampsia, defined as the presence of hypertension and
      proteinuria, is usually related with maternal and neonatal adverse effects.
      However, the exact predictor of preeclampsia is still lacking. Even though there
      are some conflicting data, mean platelet value or MPV, that is, platelet ratio
      with or without Doppler velocimetry was determined as highly sensitive markers
      for preeclampsia. We aimed to investigate the utility of MPV in prediction of
      preeclampsia. METHODS: Seventy-four preeclamptic pregnant women (21 in mild, 53
      in severe preeclampsia groups) were included in the study. To assess the
      difference of MPV between preeclamptic, normal pregnant, and healthy control
      rather than mild and severe preeclamptic pregnant women, we included in the
      analysis 31 healthy pregnant women and 35 healthy nonpregnant women. RESULTS:
      Mean age of the preeclamptic patients was 25.3 (17-38) years. Platelet levels
      were higher in mild preeclampsia (group 1) than severe preeclampsia (group 2),
      whereas alanine aminotransferase (AST), hemoglobin, and hematocrit level was
      higher in group 2. MPV levels were found to be similar in groups 1 and 2, MPV
      level increased from healthy control to preeclamptic women (P = 0.003).
      MPV:platelet ratio was similar according to the severity of preeclampsia (P =
      0.123). Doppler velocimetry did not add an additional benefit to predict
      preeclampsia or its severity. CONCLUSION: Our results showed that MPV level was
      higher in the pregnant than the control group. However, MPV did not differ both
      between mild and severe preeclampsia, and preeclampsia and non-preeclamptic
      pregnant women.

PMID- 23001989
TI  - WHO European Childhood Obesity Surveillance Initiative 2008: weight, height and
      body mass index in 6-9-year-old children.
AB  - What is already known about this subject Overweight and obesity prevalence
      estimates among children based on International Obesity Task Force definitions
      are substantially lower than estimates based on World Health Organization
      definitions. Presence of a north-south gradient with the highest level of
      overweight found in southern European countries. Intercountry comparisons of
      overweight and obesity in primary-school children in Europe based on measured
      data lack a similar data collection protocol. What this study adds Unique dataset
      on overweight and obesity based on measured weights and heights in 6-9-year-old
      children from 12 European countries using a harmonized surveillance methodology.
      Because of the use of a consistent data collection protocol, it is possible to
      perform valid multiple comparisons between countries. It demonstrates wide
      variations in overweight and obesity prevalence estimates among primary-school
      children between European countries and regions. BACKGROUND: Nutritional
      surveillance in school-age children, using measured weight and height, is not
      common in the European Region of the World Health Organization (WHO). The WHO
      Regional Office for Europe has therefore initiated the WHO European Childhood
      Obesity Surveillance Initiative. OBJECTIVE: To present the anthropometric results
      of data collected in 2007/2008 and to investigate whether there exist differences
      across countries and between the sexes. METHODS: Weight and height were measured
      in 6-9-year-old children in 12 countries. Prevalence of overweight, obesity,
      stunting, thinness and underweight as well as mean Z-scores of anthropometric
      indices of height, weight and body mass index were calculated. RESULTS: A total
      of 168 832 children were included in the analyses and a school participation rate
      of more than 95% was obtained in 8 out of 12 countries. Stunting, underweight and
      thinness were rarely prevalent. However, 19.3-49.0% of boys and 18.4-42.5% of
      girls were overweight (including obesity and based on the 2007 WHO growth
      reference).The prevalence of obesity ranged from 6.0 to 26.6% among boys and from
      4.6 to 17.3% among girls. Multi-country comparisons suggest the presence of a
      north-south gradient with the highest level of overweight found in southern
      European countries. CONCLUSIONS: Overweight among 6-9-year-old children is a
      serious public health concern and its variation across the European Region highly
      depends on the country. Comparable monitoring of child growth is possible across
      Europe and should be emphasized in national policies and implemented as part of
      action plans.

PMID- 23001991
TI  - 3,4,9,10-perylenetetracarboxylic acid/hemin nanocomposites act as redox probes
      and electrocatalysts for constructing a pseudobienzyme-channeling amplified
      electrochemical aptasensor.
AB  - A simple wet-chemical strategy for the synthesis of 3,4,9,10
      perylenetetracarboxylic acid (PTCA)/hemin nanocomposites through pi-pi
      interactions is demonstrated. Significantly, the hemin successfully conciliates
      PTCA redox activity with a pair of well-defined redox peaks and intrinsic
      peroxidase-like activity, which provides potential application of the PTCA self
      derived redox activity as redox probes. Additionally, PTCA/hemin nanocomposites
      exhibit a good membrane-forming property, which not only avoids the conventional
      fussy process for redox probe immobilization, but also reduces the participation
      of the membrane materials that act as a barrier of electron transfer. On the
      basis of these unique properties, a pseudobienzyme-channeling amplified
      electrochemical aptasensor is developed that is coupled with glucose oxidase
      (GOx) for thrombin detection by using PTCA/hemin nanocomposites as redox probes
      and electrocatalysts. With the addition of glucose to the electrolytic cell, the
      GOx on the aptasensor surface bioelectrocatalyzed the reduction of glucose to
      produce H(2)O(2), which in turn was electrocatalyzed by the PTCA/hemin
      nanocomposites. Cascade schemes, in which an enzyme is catalytically linked to
      another enzyme, can produce signal amplification and therefore increase the
      biosensor sensitivity. As a result, a linear relationship for thrombin from 0.005
      to 20 nM and a detection limit of 0.001 nM were obtained.

PMID- 23001988
TI  - Targeting Wnt pathways in disease.
AB  - Wnt-mediated signal transduction pathways have long been recognized for their
      roles in regulating embryonic development, and have more recently been linked to
      cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine
      function and bone metabolism in adults. Although therapies targeting Wnt
      signaling are attractive in theory, in practice it has been difficult to obtain
      specific therapeutics because many components of Wnt signaling pathways are also
      involved in other cellular processes, thereby reducing the specificity of
      candidate therapeutics. New technologies, and advances in understanding the
      mechanisms of Wnt signaling, have improved our understanding of the nuances of
      Wnt signaling and are leading to promising new strategies to target Wnt signaling
      pathways.

PMID- 23001990
TI  - Structural basis for proton conduction and inhibition by the influenza M2
      protein.
AB  - The influenza M2 protein forms an acid-activated and drug-sensitive proton
      channel in the virus envelope that is important for the virus lifecycle. The
      functional properties and high-resolution structures of this proton channel have
      been extensively studied to understand the mechanisms of proton conduction and
      drug inhibition. We review biochemical and electrophysiological studies of M2 and
      discuss how high-resolution structures have transformed our understanding of this
      proton channel. Comparison of structures obtained in different membrane-mimetic
      solvents and under different pH using X-ray crystallography, solution NMR, and
      solid-state NMR spectroscopy revealed how the M2 structure depends on the
      environment and showed that the pharmacologically relevant drug-binding site lies
      in the transmembrane (TM) pore. Competing models of proton conduction have been
      evaluated using biochemical experiments, high-resolution structural methods, and
      computational modeling. These results are converging to a model in which a
      histidine residue in the TM domain mediates proton relay with water, aided by
      microsecond conformational dynamics of the imidazole ring. These mechanistic
      insights are guiding the design of new inhibitors that target drug-resistant M2
      variants and may be relevant for other proton channels.

PMID- 23001992
TI  - Individual differences in spatial configuration learning predict the occurrence
      of intrusive memories.
AB  - The dual-representation model of posttraumatic stress disorder (PTSD; Brewin,
      Gregory, Lipton, & Burgess, Psychological Review, 117, 210-232 2010) argues that
      intrusions occur when people fail to construct context-based representations
      during adverse experiences. The present study tested a specific prediction
      flowing from this model. In particular, we investigated whether the efficiency of
      temporal-lobe-based spatial configuration learning would account for individual
      differences in intrusive experiences and physiological reactivity in the
      laboratory. Participants (N = 82) completed the contextual cuing paradigm, which
      assesses spatial configuration learning that is believed to depend on associative
      encoding in the parahippocampus. They were then shown a trauma film. Afterward,
      startle responses were quantified during presentation of trauma reminder pictures
      versus unrelated neutral and emotional pictures. PTSD symptoms were recorded in
      the week following participation. Better configuration learning performance was
      associated with fewer perceptual intrusions, r = -.33, p < .01, but was unrelated
      to physiological responses to trauma reminder images (ps > .46) and had no direct
      effect on intrusion-related distress and overall PTSD symptoms, rs > -.12, ps >
      .29. However, configuration learning performance tended to be associated with
      reduced physiological responses to unrelated negative images, r = -.20, p = .07.
      Thus, while spatial configuration learning appears to be unrelated to affective
      responding to trauma reminders, our overall findings support the idea that the
      context-based memory system helps to reduce intrusions.

PMID- 23001993
TI  - Feasibility of electroextraction as versatile sample preconcentration for fast
      and sensitive analysis of urine metabolites, demonstrated on acylcarnitines.
AB  - In this work, we demonstrate the applicability of electroextraction (EE) to urine
      metabolites. To investigate which urine metabolite classes are susceptible to EE,
      off-line EE experiments were carried out with a prototype device, in which urine
      metabolites were electroextracted from ethyl acetate into water. The obtained
      extracts were examined with direct infusion MS and the results demonstrated that
      several compound classes could be extracted, amongst which amino acids and
      acylcarnitines. Acylcarnitines were selected for evaluation of the performance of
      EE. For this, the EE setup was adapted to capillary EE (cEE) to be able to
      analyze large urine sample series, and it was coupled online to LC-MS. cEE-LC-MS
      of acylcarnitines was optimized and characterized. The recovery, linearity,
      repeatability, and detection limit of the cEE-LC-MS method was good to excellent.
      To demonstrate the versatility of EE for sample preparation in analytical
      procedures, extracts were injected into a CZE-MS system, resulting in detection
      of the acylcarnitines along with more than 100 presumed metabolite peaks. The
      results presented here indicate that EE can be used as a fast sample
      preconcentration technique of low abundant urine metabolites, in combination with
      both LC and CZE.

PMID- 23001994
TI  - Chiral aryl-copper(III) electrophiles: new opportunities in catalytic
      enantioselective arylations and domino processes.
AB  - "Chiral aryl cation" equivalents: The combination of diaryliodonium salts and
      catalytic amounts of chiral copper complexes provides facile access to "chiral
      aryl cation" synthons. These reagents offer new possibilities for asymmetric
      arylation reactions that initiate further domino processes.

PMID- 23001995
TI  - Derivatization of chiral carboxylic acids with (S)-anabasine for increasing
      detectability and enantiomeric separation in LC/ESI-MS/MS.
AB  - A simple and practical derivatization procedure for increasing the detectability
      and enantiomeric separation of chiral carboxylic acids in LC/ESI-MS/MS has been
      developed. (S)-Anabasine (ANA) was used as the derivatization reagent and rapidly
      reacted with carboxylic acids [3-hydroxypalmitic acid (3-OH-PA), 2-(beta
      carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman (gamma-CEHC), and etodolac] in the
      presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholium chloride. The
      resulting ANA-derivatives were highly responsive in ESI-MS operating in the
      positive-ion mode and gave characteristic product ions during MS/MS, which
      enabled sensitive detection using selected reaction monitoring; the detection
      responses of the ANA-derivatives were increased by 20-160-fold over those of the
      intact carboxylic acids and the limits of detection were in the low femtomole
      range (1.8-11 fmol on the column). The ANA-derivatization was also effective for
      the enatiomeric separation of the chiral carboxylic acids; the resolution was
      1.92, 1.75, and 2.03 for 3-OH-PA, gamma-CHEC, and etodolac, respectively. The
      derivatization procedure was successfully applied to a biological sample
      analysis; the derivatization followed by LC/ESI-MS/MS enabled the separation and
      detection of trace amounts of 3-OH-PA in neonatal dried blood spot and gamma-CEHC
      in human saliva with a simple pretreatment and small sample volume.

PMID- 23001996
TI  - BC(50): a generalized, unifying affinity descriptor.
AB  - Assessing binding affinities is an unavoidable step that we come across any time
      interactions between binding species are investigated. A quantitative evaluation
      of binding affinities relies on the determination of binding constants but,
      whilst the binding constant fully defines the affinity of a reagent for a ligand
      when only one complex species is formed, the same is not true when the
      interacting partners form more than one complex of different stoichiometry,
      because all complexes contribute to the overall binding affinity. Unfortunately,
      this situation is the rule rather than the exception in chemical systems, but a
      generally accepted solution for this issue has not yet been settled. In this
      Personal Account, we describe the evolution, from the initial idea to a fully
      developed stage, of a binding descriptor that has been developed with the aim of
      filling this gap, thereby providing scientists in all fields of chemistry with a
      unifying tool for the assessment of binding affinities based on the knowledge of
      the binding constants in systems that involve any number of complex species.

PMID- 23001997
TI  - Identification of a susceptibility locus in STAT4 for Behcet's disease in Han
      Chinese in a genome-wide association study.
AB  - OBJECTIVE: To identify susceptibility loci for Behcet's disease (BD) and
      elucidate their functional role. METHODS: A genome-wide association study (GWAS)
      and functional studies were conducted. A total of 149 patients and 951 controls
      were enrolled in the initial GWAS, and 554 patients and 1,159 controls were
      enrolled in the replication study. Real-time polymerase chain reaction,
      luciferase reporter assay, and enzyme-linked immunosorbent assay were performed.
      RESULTS: Our GWAS and replication studies identified a susceptibility locus
      around STAT4 (single-nucleotide polymorphisms [SNPs] rs7574070, rs7572482, and
      rs897200; P = 3.36 * 10(-7)  to 6.20 * 10(-9) ). Increased expression of STAT4
      was observed in individuals carrying the rs897200 risk genotype AA. Consistent
      with the idea that STAT4 regulates the production of interleukin-17 (IL-17) and
      interferon-gamma, IL17 messenger RNA and protein levels were increased in
      individuals carrying the rs897200 risk genotype AA. Interestingly, the risk
      allele A of rs897200 creates a putative transcription factor binding site. To
      test whether it directly affects STAT4 transcription, an in vitro luciferase
      reporter gene assay was performed. Higher transcription activity was observed in
      individuals carrying the risk allele A, suggesting that rs897200 is likely to
      directly affect STAT4 expression. Additionally, 2 SNPs, rs7574070 and rs7572482,
      which are tightly linked with rs897200, were cis-expression quantitative trait
      loci (eQTL) SNPs, suggesting that SNP rs897200 is an eQTL SNP. Most importantly,
      the clinical disease severity score was higher in individuals with the rs897200
      risk genotype AA. CONCLUSION: These findings strongly suggest that STAT4 is a
      novel locus underlying BD. We propose a model in which up-regulation of STAT4
      expression and subsequent STAT4-driven production of inflammatory cytokines, such
      as IL-17, constitute a potential pathway leading to BD.

PMID- 23001998
TI  - Mouse models of DNA polymerases.
AB  - In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of
      DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this
      contribution, which included the isolation and characterization of Escherichia
      coli DNA polymerase I. Now there are 15 known DNA polymerases in mammalian cells
      that belong to four different families. These DNA polymerases function in many
      different cellular processes including DNA replication, DNA repair, and damage
      tolerance. Several biochemical and cell biological studies have provoked a
      further investigation of DNA polymerase function using mouse models in which
      polymerase genes have been altered using gene-targeting techniques. The
      phenotypes of mice harboring mutant alleles reveal the prominent role of DNA
      polymerases in embryogenesis, prevention of premature aging, and cancer
      suppression.

PMID- 23001999
TI  - Parental perceptions of and concerns about child's body weight in eight European
      countries--the IDEFICS study.
AB  - OBJECTIVES: To evaluate parental perceptions of and concern about child's body
      weight and general health in children in a European cohort. DESIGN: Cross
      sectional multi-centre study in eight European countries. PARTICIPANTS: 16,220
      children, ages 2-9 years. METHODS: Parents completed a questionnaire regarding
      children's health and weight and concern about overweight and underweight.
      Objective children's weight categories from the International Obesity Task Force
      were used. Logistic regression models were utilized to identify predictors of
      accurate weight perception. RESULTS: Parental weight perception corresponded
      overall to children's mean body mass index (BMI) z-scores, with important
      exceptions. About one-third of the total indicated concern about underweight,
      paradoxically most often parents of children in the overweight or obesity
      categories. In 63%, parents of children in the overweight category marked 'proper
      weight'. The strongest predictor for accurate parental weight perception for
      children with overweight and obesity was BMI z-score (odds ratio [OR] = 7.2, 95%
      confidence interval [CI] 6.1-8.7). Compared to Southern Europe, ORs for accurate
      parental weight perception were 4.4 (95% CI 3.3-6.0) in Northern Europe and 3.4
      (95% CI 2.7-4.2) in Central Europe. CONCLUSION: Parents of children categorized
      as being overweight or obese systematically underestimated weight. Parents
      differed regionally regarding accurate weight perception and concern about
      overweight and underweight.

PMID- 23002000
TI  - Organocatalytic aza-Michael-Michael cascade reactions: a flexible approach to
      2,3,4-trisubstituted tetrahydroquinolines.
AB  - Cascading like dominos: An efficient and highly enantioselective synthesis of
      2,3,4-trisubstituted tetrahydroquinolines through cascade aza-Michael-Michael
      reactions was developed. Tetrahydroquinolines were obtained in excellent yields,
      high enantioselectivities, and good diastereoselectivities, and could be easily
      transformed into ring-fused tetrahydroquinolines (see scheme).

PMID- 23002001
TI  - Non-stoichiometric polycondensations and the synthesis of high molar mass
      polycondensates.
AB  - This report presents a general overview of non-stoichiometric step-growth
      polymerizations (polycondensations). Three kinds of non-stoichiometric
      polycondensations are defined and discussed for a(2)  + b(2)  monomer
      combinations. Depending on the kinetic scenario and on the experimental
      conditions, the excess of one monomer either strongly reduces or strongly
      enhances the average degree of polymerization (DP) relative to a stoichiometric
      polycondensation under identical conditions. As a result, telechelic oligomers or
      extremely high molar mass polymers (DPs > 1000) may be formed. Stoichiometric
      imbalance has in all cases the consequence that cyclization is largely suppressed
      in early stages of a polycondensation. Finally, non- stoichiometric "a(2)  + b(n)
      " polycondensations are discussed.

PMID- 23002002
TI  - Graphene from molecules.
AB  - Step by step: According to the molecular approach to the production of graphene,
      precursor molecules are cross-linked to form two-dimensional intermediates, and
      pyrolysis transforms the intermediates into graphene. This type of highly
      efficient synthesis of high-quality graphene is crucial to the development of
      innovative applications.

PMID- 23002003
TI  - A protocol for stripping and reprobing of Western blots originally developed with
      colorimetric substrate TMB.
AB  - Western blotting is a widely used analytical technique for detection of specific
      protein(s) in a given sample of tissue/cell homogenate or extract. Both
      chemiluminescence (CL) and colorimetric detections can be used for imaging
      Western blots. Colorimetric substrates offer background free, sensitive, and
      clean imaging results directly on the blotted membrane and provides more accurate
      profile with respect to prestained marker. However, blots stained with
      colorimetric substrates cannot be reused since no stripping protocols have been
      reported for such blots, thus limiting their reuse for detection of another
      protein. In the present study, for the first time, we report a novel method of
      stripping Western blots developed with the colorimetric substrate TMB for
      detection of a low-abundant protein and reprobing of these blots after stripping
      for detection of a more abundant protein through CL procedure. The stripping
      procedure utilizes a stripping buffer consisting of beta-mercaptoethanol, SDS,
      and Tris-HCl and a washing buffer consisting of PBS added with 0.1% Tween-20
      involves a series of steps and facilitates accurate detection of the second
      protein (i.e., more abundant protein) in the stripped blot through CL. The
      protocol is reproducible and facilitates saving of precious clinical samples, in
      addition to saving cost and time as compared to the existing procedures.

PMID- 23002004
TI  - Application of ionic liquid in liquid phase microextraction technology.
AB  - Ionic liquids (ILs) are novel nonmolecular solvents. Their unique properties,
      such as high thermal stability, tunable viscosity, negligible vapor pressure,
      nonflammability, and good solubility for inorganic and organic compounds, make
      them excellent candidates as extraction media for a range of microextraction
      techniques. Many physical properties of ILs can be varied, and the structural
      design can be tuned to impart the desired functionality and enhance the analyte
      extraction selectivity, efficiency, and sensitivity. This paper provides an
      overview of the applications of ILs in liquid phase microextraction technology,
      such as single-drop microextraction, hollow fiber based liquid phase
      microextraction, and dispersive liquid-liquid microextraction. The sensitivity,
      linear calibration range, and detection limits for a range of target analytes in
      the methods were analyzed to determine the advantages of ILs in liquid phase
      microextraction.

PMID- 23002005
TI  - Peritoneal sarcomatosis in pediatric malignancies.
AB  - Peritoneal sarcomatosis (PSC) is defined as peritoneal involvement of multiple
      sarcomatous tumors. Desmoplastic small round cell tumors (DSRCT) and
      rhabdomyosarcomas are the most common pediatric PSC cases. PSC has been treated
      with chemotherapy and mainly palliative surgery, but long-term outcome has been
      poor. New imaging technologies have improved the evaluation of disease extent and
      patterns of peritoneal dissemination, and cytoreductive surgery followed by
      hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated as a
      treatment option to prolong remission in pediatric patients. We will review the
      clinical characteristics, potential biologic mechanisms, radiographic
      characteristics, and potential therapies for pediatric PSC patients.

PMID- 23002007
TI  - Asymmetric formal [3+2] cycloaddition reaction of alpha-aryl isocyanoesters with
      N-aryl maleimides by bifunctional cinchona alkaloids-based squaramide/AgSbF6
      cooperative catalysis.
AB  - It is better to be cooperative: A highly diastereo- and enantioselective
      asymmetric [3+2] cycloaddition reaction of alpha-aryl isocyanoacetates with N
      aryl maleimides through cooperative catalysis of cinchona alkaloid-derived
      squaramide/AgSbF(6) was developed. A wide range of optically active, substituted
      1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c] pyrrole derivatives was obtained in high
      yields (up to 98%), high diastereoselectivities (>20:1 d.r.), and good to
      excellent enantioselectivities (up to 92% ee) under mild reaction conditions.

PMID- 23002006
TI  - Efficacy of B cell depletion therapy for murine joint arthritis flare is
      associated with increased lymphatic flow.
AB  - OBJECTIVE: B cell depletion therapy ameliorates rheumatoid arthritis by
      mechanisms that are incompletely understood. Arthritis flare in tumor necrosis
      factor (TNF)-transgenic mice is associated with efferent lymph node (LN)
      "collapse," triggered by B cell translocation into lymphatic spaces and decreased
      lymphatic drainage. The aim of this study was to examine whether the efficacy of
      B cell depletion therapy is associated with restoration of lymphatic drainage due
      to removal of obstructing nodal B cells. METHODS: We used contrast-enhanced
      magnetic resonance imaging, indocyanine green near-infrared imaging, and
      intravital immunofluorescence imaging to longitudinally assess synovitis,
      lymphatic flow, and cell migration in lymphatic vessels in TNF-transgenic mice.
      We conducted tests to determine whether the efficacy of B cell depletion therapy
      is associated with restoration of lymphatic draining and cell egress from
      arthritic joints. RESULTS: Unlike active lymphatics to normal and prearthritic
      knees, afferent lymphatic vessels to collapsed LNs in inflamed knees do not
      pulse. Intravital immunofluorescence imaging demonstrated that CD11b+
      monocyte/macrophages in lymphatic vessels afferent to expanding LNs travel at
      high velocity (mean+/-SD 186+/-37 MUm/second), while these cells are stationary
      in lymphatic vessels afferent to collapsed popliteal LNs. B cell depletion
      therapy for arthritis flares in TNF-transgenic mice significantly decreased knee
      synovium volume (by 50% from the baseline level) and significantly increased
      lymphatic clearance compared with placebo (P<0.05). This increased lymphatic
      drainage restored macrophage egress from inflamed joints without recovery of the
      lymphatic pulse. CONCLUSION: These results support a novel mechanism in which B
      cell depletion therapy for joint arthritis flares lessens inflammation by
      increasing lymphatic drainage and subsequent migration of cells and cytokines
      from the synovial space.

PMID- 23002009
TI  - Observation of multiphoton-induced fluorescence from graphene oxide nanoparticles
      and applications in in vivo functional bioimaging.
AB  - Lightening organelles: A femtosecond laser can excite multiphoton-induced
      luminescence of graphene oxide nanoparticles. The flow, distributions, and
      clearance of intravenously injected GO-PEG nanoparticles in the blood vessel of
      mice could be observed clearly by two-photon imaging. The 3D distribution of
      microinjected GO-PEG nanoparticles in a mice brain could also be reconstructed
      with two-photon microscopy.

PMID- 23002008
TI  - Activation of KCNN3/SK3/K(Ca)2.3 channels attenuates enhanced calcium influx and
      inflammatory cytokine production in activated microglia.
AB  - In neurons, small-conductance calcium-activated potassium (KCNN/SK/K(Ca)2)
      channels maintain calcium homeostasis after N-methyl-D-aspartate (NMDA) receptor
      activation, thereby preventing excitotoxic neuronal death. So far, little is
      known about the function of KCNN/SK/K(Ca)2 channels in non-neuronal cells, such
      as microglial cells. In this study, we addressed the question whether
      KCNN/SK/K(Ca)2 channels activation affected inflammatory responses of primary
      mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N
      cyclohexyl-N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA), a
      positive pharmacological activator of KCNN/SK/K(Ca)2 channels, significantly
      reduced LPS-stimulated activation of microglia in a concentration-dependent
      manner. The general KCNN/SK/K(Ca)2 channel blocker apamin reverted these effects
      of CyPPA on microglial proliferation. Since calcium plays a central role in
      microglial activation, we further addressed whether KCNN/SK/K(Ca)2 channel
      activation affected the changes of intracellular calcium levels, [Ca(2+)](i), in
      microglial cells. Our data show that LPS-induced elevation of [Ca(2+)](i) was
      attenuated following activation of KCNN2/3/K(Ca)2.2/K(Ca)2.3 channels by CyPPA.
      Furthermore, CyPPA reduced downstream events including tumor necrosis factor
      alpha and interleukin 6 cytokine production and nitric oxide release in activated
      microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/K(Ca)2
      channel subtypes to identify which particular channel subtype mediated the
      observed anti-inflammatory effects. Only inhibitory peptides targeting
      KCNN3/SK3/K(Ca)2.3 channels, but not KCNN2/SK2/K(Ca)2.2 channel inhibition,
      reversed the CyPPA-effects on LPS-induced microglial proliferation. These
      findings revealed that KCNN3/SK3/K(Ca)2.3 channels can modulate the LPS-induced
      inflammatory responses in microglial cells. Thus, KCNN3/SK3/K(Ca)2.3 channels may
      serve as a therapeutic target for reducing microglial activity and related
      inflammatory responses in the central nervous system.

PMID- 23002010
TI  - Laser beam measurement of abdominal sagittal diameter in obese children: a
      validation study.
AB  - OBJECTIVES: Sagittal diameter (SAD) has been reported to correlate to visceral
      fat and cardiovascular risk factors. SAD is measured with the individual lying
      down, halfway between the lower rib margin and the iliac crest; it represents the
      mid-height of the abdomen. The aim of this study was to validate SAD measured
      using a recently-developed laser beam device (SAD(LDB) ) against SAD measured
      using MRI (SAD(MRI)). METHODS: Of 48 obese children (25 boys, 23 girls) aged 9-11
      years on the waiting list for obesity treatment, 34 agreed to a baseline
      measurement, which was followed by repeated measurements 6 and 12 months later in
      31 and 22 children respectively. MRI was used to examine SAD(MRI) at 5 cm above
      (SAD(MRI,cra) ) and below (SAD(MRI,cau)) the mid plane of the L4-5 intervertebral
      disc. RESULTS: Each of the differences SAD(LBD) - SAD(MRI, cau) and SAD(LBD) -
      SAD(MRI,cra) was subjected to a repeated-measurements ANOVA; the visit did not
      have a statistically significant effect in either case (p = 0.19 and p = 0.72,
      respectively). The difference SAD(LBD) - SAD(MRI, cau) was 1.50 on average (p <
      0.0001; CI 1.26-1.74) while the corresponding figure for SAD(LBD) -SAD(MRI, cra)
      was 1.26 (p < 0.0001; CI 1.04-1.49). Regression of the difference on the mean
      gave slopes of -0.09 (p = 0.25) and -0.04 (p = 0.57) respectively. Prediction of
      SAD(MRI) from SAD(LDB) can be performed in different ways: by means of linear
      regression or by means of an additive correction. CONCLUSIONS: Thus, this laser
      device can be used instead of MRI to estimate SAD by using a simple correction.

PMID- 23002011
TI  - Profiling of erythropoietin products by capillary electrophoresis with native
      fluorescence detection.
AB  - The potential of CE with native fluorescence detection (Flu) for the profiling of
      the therapeutic protein erythropoietin (EPO) was studied. EPO is a highly
      heterogeneous glycoprotein comprising a large number of isoforms. CE was applied
      to induce separation among the various glycoforms. Native Flu of EPO provided
      high detection selectivity yielding good signal-to-noise ratios and stable
      baselines, particularly when compared to conventional UV absorbance detection. In
      order to enhance EPO isoform resolution, CE was performed using a capillary with
      a neutral coating in combination with a simple BGE of 2.0 M acetic acid (pH 2.1).
      CE-Flu analysis of the EPO biological reference preparation of the European
      Pharmacopeia resulted in a highly detailed glycoform profile. Migration time RSDs
      for selected EPO isoforms were less than 0.22% and 0.80% for intraday and
      interday repeatability, respectively. RSDs for relative peak intensity of the
      major EPO isoforms were less than 3%. The achieved resolution, migration time
      stability, and sensitivity allowed discrimination of different EPO products (EPO
      alpha and EPO-beta) based on the recorded glycoform pattern. The developed CE-Flu
      method is relatively straightforward, and shows potential for quality control in
      biopharmaceutical production.

PMID- 23002012
TI  - Tumors of the cervical sympathetic chain--diagnosis and management.
AB  - BACKGROUND: Tumors originating from the cervical sympathetic chain are uncommon
      but important entities in the differential diagnosis of parapharyngeal space
      masses. METHODS: We conducted a retrospective review of patients presenting with
      tumors of the cervical sympathetic chain. RESULTS: Twenty-four patients presented
      between 1994 and 2010. Presenting symptoms were dysphagia (n = 7.29%), neck mass
      (n = 7.29%), throat fullness (n = 4.17%), and Horner syndrome (n = 2.8%).
      Although radiologic images showed classic lateral displacement of the carotid
      arteries in 10 patients (42%), in 9 patients (38%) the radiologic findings
      demonstrated splaying of the carotid arteries similar to carotid body tumor, and
      in 5 patients (20%), the findings were indeterminate. Twenty-one patients
      underwent surgical removal of the tumors with pathology revealing 10
      paragangliomas, 10 schwannomas, and 1 neurofibroma. Horner (57%) and first-bite
      (33%) syndromes were the most common complications. CONCLUSIONS: Although
      anterolateral displacement of the carotids is suggestive of a sympathetic tumor,
      absence of these findings does not rule out this entity. To this end, we have
      included in this review a guide to preoperative radiologic diagnosis of
      parapharyngeal space lesions.

PMID- 23002013
TI  - Pelvic Ewing sarcoma mimicking sacroiliitis.

PMID- 23002016
TI  - Rapid screening and determination of 4-chloroamphetamine in saliva by paper spray
      mass spectrometry and capillary electrophoresis-mass spectrometry.
AB  - A novel drug-screening system, consisting of paper spray-MS (PS-MS) and a CE-ESI
      MS method was developed. This system can be easily switched either to PS-MS for
      rapidly screening samples or to the traditional CE-ESI-MS method for separation
      and to obtain detailed mass spectral information, while sharing the same mass
      spectrometer. In the former case, when a sharp (15 degrees -tip) chromatography
      paper was used, the optimized distance from the paper tip to the mass inlet was
      7.7 mm, whereas the optimized distance for the CE-ESI tip was ~13.5 mm. Using 4
      chloroamphetamine as a model compound, the LODs for PS-MS and CE-ESI-MS were
      determined to ~0.1 and 0.25 ppm, respectively. Comparisons of results obtained
      using PS-MS and CE-ESI-MS and the experimental conditions are described.

PMID- 23002014
TI  - The T-cell response to HIV.
AB  - HIV is a disease in which the original clinical observations of severe
      opportunistic infections gave the first clues regarding the underlying pathology,
      namely that HIV is essentially an infection of the immune system. HIV infects and
      deletes CD4(+) T cells that normally coordinate the adaptive T- and B-cell
      response to defend against intracellular pathogens. The immune defect is
      immediate and profound: At the time of acute infection with an AIDS virus,
      typically more than half of the gut-associated CD4(+) T cells are depleted,
      leaving a damaged immune system to contend with a life-long infection.

PMID- 23002017
TI  - Mechanism of the Pd-catalyzed decarboxylative allylation of alpha-imino esters:
      decarboxylation via free carboxylate ion.
AB  - The Pd-catalyzed decarboxylative allylation of alpha-(diphenylmethylene)imino
      esters (1) or allyl diphenylglycinate imines (2) is an efficient method to
      construct new C(sp(3))-C(sp(3)) bonds. The detailed mechanism of this reaction
      was studied by theoretical calculations [ONIOM(B3LYP/LANL2DZ+p:PM6)] combined
      with experimental observations. The overall catalytic cycle was found to consist
      of three steps: oxidative addition, decarboxylation, and reductive allylation.
      The oxidative addition of 1 to [(dba)Pd(PPh(3))(2)] (dba = dibenzylideneacetone)
      produces an allylpalladium cation and a carboxylate anion with a low activation
      barrier of +9.1 kcal mol(-1). The following rate-determining decarboxylation
      proceeds via a solvent-exposed alpha-imino carboxylate anion rather than an O
      ligated allylpalladium carboxylate with an activation barrier of +22.7 kcal mol(
      1). The 2-azaallyl anion generated by this decarboxylation attacks the face of
      the allyl ligand opposite to the Pd center in an outer-sphere process to produce
      major product 3, with a lower activation barrier than that of the minor product
      4. A positive linear Hammett correlation [rho = 1.10 for the PPh(3) ligand] with
      the observed regioselectivity (3 versus 4) supports an outer-sphere pathway for
      the allylation step. When Pd combined with the bis(diphenylphosphino)butane
      (dppb) ligand is employed as a catalyst, the decarboxylation still proceeds via
      the free carboxylate anion without direct assistance of the cationic Pd center.
      Consistent with experimental observations, electron-withdrawing substituents on 2
      were calculated to have lower activation barriers for decarboxylation and, thus,
      accelerate the overall reaction rates.

PMID- 23002015
TI  - Animal models of Alzheimer disease.
AB  - Significant insights into the function of genes associated with Alzheimer disease
      and related dementias have occurred through studying genetically modified
      animals. Although none of the existing models fully reproduces the complete
      spectrum of this insidious human disease, critical aspects of Alzheimer pathology
      and disease processes can be experimentally recapitulated. Genetically modified
      animal models have helped advance our understanding of the underlying mechanisms
      of disease and have proven to be invaluable in the preclinical evaluation of
      potential therapeutic interventions. Continuing refinement and evolution to yield
      the next generation of animal models will facilitate successes in producing
      greater translational concordance between preclinical studies and human clinical
      trials and eventually lead to the introduction of novel therapies into clinical
      practice.

PMID- 23002018
TI  - Characterization of pigments and ligands in a wall painting fragment from
      Liternum archaeological park (Italy).
AB  - Spectroscopic and MS techniques were used to characterize the pigments and the
      composition of polar and nonpolar binders of a stray wall painting fragment from
      Liternum (Italy) archaeological excavation. X-ray fluorescence and diffraction
      analysis of the decorations indicated mainly the presence of calcite, quartz,
      hematite, cinnabar, and cuprorivaite. Infrared spectroscopy, GC coupled to flame
      ionization detector, and MS analysis of the polar and nonpolar components
      extracted from paint layers from three different color regions revealed the
      presence of free amino acids, sugars, and fatty acids. Interestingly, LC-MS
      shotgun analysis of the red painting region showed the presence of alphaS1-casein
      of buffalo origin. Compared to our previous results from Pompeii's wall
      paintings, even though the Liternum painting mixture contained also binders of
      animal origin, the data strongly suggest that in both cases a tempera painting
      technique was utilized.

PMID- 23002020
TI  - Probing the selectivity of azomethine imine cycloaddition to single-walled carbon
      nanotubes by resonance Raman spectroscopy.
AB  - Selective covalent surface modification of single-walled carbon nanotubes (SWNTs)
      is of great importance to various carbon nanotube-based applications as it might
      offer an alternative method for enriching metallic and semiconducting nanotubes.
      Herein, we report on the surface modification of SWNTs through 1,3-dipolar
      cycloaddition of 3-phenyl-phthalazinium-1-olate, which is a stable and reactive
      azomethine imine. For this reaction, microwave heating was found to be more
      efficient than conventional and solvent-free heating. The sensitivity of
      cycloaddition to the molecular structure of SWNTs was probed using resonance
      Raman spectroscopy with three different laser excitations. Based on the obtained
      results, azomethine imine addition to the surface of nanotubes is selective for
      metallic and large-diameter semiconducting SWNTs. Thermogravimetric analysis
      coupled with mass spectrometry showed that fragments released at high
      temperatures corresponded to the phenylphthalazine group, thus confirming the
      covalent surface functionalization. Modified SWNTs were further characterized by
      X-ray photoelectron and UV/Vis-NIR spectroscopies.

PMID- 23002019
TI  - Initial testing (stage 1) of the phosphatidylinositol 3' kinase inhibitor,
      SAR245408 (XL147) by the pediatric preclinical testing program.
AB  - BACKGROUND: Activation of the PI3 kinase pathway occurs frequently in many adult
      cancers and is implicated in tumor cell proliferation, survival, and resistance
      to chemotherapy and radiotherapy. However, less is known regarding the relevance
      of this pathway in pediatric cancers. Here we have evaluated SAR245408, a novel
      small molecule PI3K inhibitor, against childhood cancer cell lines and
      xenografts. PROCEDURES: SAR245408 was tested against the PPTP in vitro cell line
      panel at concentrations from 10 to 100 uM and against the PPTP in vivo xenograft
      panels at a dose of 100 mg/kg administered orally daily * 14. RESULTS: In vitro
      SAR245408 demonstrated cytotoxic activity, with a median relative IC50 value of
      10.9 uM (range 2.7-24.5 uM). SAR245408 was well tolerated in vivo, and all 44
      tested xenograft models were evaluable for efficacy. SAR245408 induced
      significant differences in EFS distribution compared to control in 29 of 37 (79%)
      of solid tumor xenografts and in two of seven (29%) ALL xenografts. SAR245408
      induced tumor growth inhibition meeting criteria for intermediate EFS T/C
      activity (EFS T/C > 2) in 4 of 37 (11%) solid tumor xenografts. Intermediate EFS
      T/C activity was also observed for two of seven (29%) evaluable ALL xenografts.
      Objective responses were not observed for solid tumor or for ALL xenografts.
      CONCLUSIONS: Under the conditions evaluated in this study, SAR245408 achieved
      modest single-agent activity against most PPTP preclinical models. Further
      exploration of SAR245408 in combination with standard agents or with other
      signaling inhibitors could be considered.

PMID- 23002021
TI  - Eggshell-inspired biomineralization generates vaccines that do not require
      refrigeration.
AB  - We're not gonna bake it: In situ biomineralization creates an egg-like shell on
      vaccine particles to improve their thermostability. Different from the bare
      vaccine (squares), the biomineralized vaccine (red circles) can be stored at
      ambient temperature without refrigeration for up to a week and retain biological
      activity both in vitro (see graph), as well as in a mouse model.

PMID- 23002022
TI  - Development and validation of a new disease activity index as a numerical sum of
      four variables in patients with early arthritis.
AB  - OBJECTIVE: To describe the development and validation of a disease activity index
      in early arthritis that can be easily applied in daily practice and clinical
      research. METHODS: The Hospital Universitario La Princesa Index (HUPI) was
      developed after analysis of data from an early arthritis cohort (202 patients
      with 756 visits). It is the sum of 4 variables (graded 0-3): tender joint count,
      swollen joint count, patient global assessment, and acute-phase reactants
      (erythrocyte sedimentation rate [ESR] and/or C-reactive protein [CRP] level,
      depending on availability at the moment of evaluation). The score for each
      variable was based on its quartile distribution in the cohort. The HUPI was
      validated using the following properties: feasibility, internal consistency
      (Cronbach's alpha), convergent validity (Pearson's r coefficients with other
      activity measures), criterion validity (area under the receiver operating
      characteristic curve [AUC ROC] to detect minimal disease activity [MDA]), and
      sensitivity to change (AUC ROC) to detect change with the physician's and
      patient's assessment of disease activity. RESULTS: Internal consistency is
      reasonable (alpha = 0.63). The HUPI correlates well with activity measures such
      as the Disease Activity Score in 28 joints (DAS28; r = 0.89) and the Simplified
      Disease Activity Index (SDAI; r = 0.70), and correlates slightly worse with the
      functional index of the Health Assessment Questionnaire (r = 0.69). It
      discriminates MDA correctly (AUC 0.95), and its sensitivity to change is slightly
      superior (AUC 0.902) to that of the DAS28-ESR (AUC 0.864), the DAS28-CRP (AUC
      0.889), and the SDAI (AUC 0.791). CONCLUSION: The HUPI has face validity, is easy
      to calculate, is sensitive, and is a valid composite index for the assessment of
      disease activity in patients with early arthritis, both in clinical research and
      in routine care.

PMID- 23002023
TI  - Primary squamous cell carcinoma of the thyroid gland: a case report and review.
AB  - BACKGROUND: Primary squamous cell carcinoma (SCC) of the thyroid gland is a rare
      malignancy that presents with advanced disease and poor prognosis. METHODS: A 75
      year-old woman with a history of Hashimoto thyroiditis presented with 6 months of
      dysphagia and stridor. Imaging revealed a thyroid mass invading the larynx.
      Primary SCC of the thyroid was diagnosed by histopathologic and
      immunohistochemical evaluation. Total thyroidectomy, total laryngectomy,
      bilateral modified neck dissection, and adjuvant radiotherapy (RT) were
      performed. Radiologic follow-up at 21 months demonstrated no disease and total
      length of survival was 31 months. RESULTS: Despite an aggressive T4aN0M0 tumor,
      survival in this case was more than double the median survival rate previously
      reported. Concomitant Hashimoto thyroiditis is rare and histopathologic and
      immunohistochemical evaluation is imperative for an accurate diagnosis.
      CONCLUSION: The case and literature reported here support that a thorough
      diagnostic workup of primary SCC of the thyroid with aggressive locoregional
      surgery and adjuvant RT may improve the length of survival.

PMID- 23002024
TI  - Visual short-term memory always requires general attention.
AB  - The role of attention in visual memory remains controversial; while some evidence
      has suggested that memory for binding between features demands no more attention
      than does memory for the same features, other evidence has indicated cognitive
      costs or mnemonic benefits for explicitly attending to bindings. We attempted to
      reconcile these findings by examining how memory for binding, for features, and
      for features during binding is affected by a concurrent attention-demanding task.
      We demonstrated that performing a concurrent task impairs memory for as few as
      two visual objects, regardless of whether each object includes one or more
      features. We argue that this pattern of results reflects an essential role for
      domain-general attention in visual memory, regardless of the simplicity of the to
      be-remembered stimuli. We then discuss the implications of these findings for
      theories of visual working memory.

PMID- 23002025
TI  - Nutritional status of adolescents with hematological malignancies, bone tumors,
      and other solid tumors during the first year after diagnosis.

PMID- 23002026
TI  - Composite cryogel with immobilized concanavalin A for affinity chromatography of
      glycoproteins.
AB  - Composite cryogels containing porous adsorbent particles were prepared under
      cryogelation conditions. The composites with immobilized concanavalin A (Con A)
      were used for capturing glycoproteins. Adsorbent particles were introduced into
      the structure in order to improve the capacity and to facilitate the handling of
      the particles. The monolithic composite cryogels were produced from suspensions
      of polyvinyl alcohol particles and porous adsorbent particles and cross-linked
      under acidic conditions at sub-zero temperature. The cryogels were epoxy
      activated and Con A was immobilized as an affinity ligand. Binding and elution of
      horseradish peroxidase (HRP) was studied in batch experiment and in a
      chromatographic setup. Increasing adsorbent concentration in composite cryogels
      will increase ligand density, which therefore enhances the amount of bound HRP
      from 0.98 till 2.9 (milligram enzyme per milliliter of gel) in the
      chromatographic system. The material was evaluated in 10 cycles for binding and
      elution of HRP.

PMID- 23002027
TI  - An unusual cause of diffuse pulmonary infiltrates.

PMID- 23002028
TI  - Access to sultams by rhodium(III)-catalyzed directed C-H activation.
AB  - Director's cut: The pharmaceutically relevant sulfonamide group is shown to be a
      competent directing group for [Cp*Rh(OAc)(2)]-catalyzed C-H functionalizations.
      Reactions of the cyclometalated intermediate with internal alkynes provide access
      to a wide range of sultam derivatives. The reaction is high yielding and works
      best under aerobic conditions with catalytic amounts of CuOAc as an oxidation
      mediator. Cp* = C(5)Me(5).

PMID- 23002029
TI  - Surgical management of inverted papilloma: approaching a new standard for
      surgery.
AB  - BACKGROUND: Inverted papilloma surgery is currently performed primarily with an
      endoscopic approach, a technique that has a recurrence rate of 12%. However, a
      recent study reported a recurrence rate of 5% with a strategy based on
      subperiosteal dissection of the tumor, with limited indications for using an
      external approach. The aim of this work was to evaluate whether different teams
      using the same surgical concepts could reproduce the excellent results that were
      recently reported. METHODS: This study is a retrospective chart review of 71
      consecutive patients with inverted papilloma who were treated during the last 10
      years. RESULTS: In all, 80% of the patients were treated using a purely
      endoscopic approach. The mean follow-up period was 31.6 months. The recurrence
      rate was 3.3% for cases with at least a 12-month follow-up. CONCLUSIONS: This
      work confirms the results described in recent literature and further supports
      transnasal endoscopic surgery to manage inverted papilloma.

PMID- 23002030
TI  - Early cisplatin induced ototoxicity profile may predict the need for hearing
      support in children with medulloblastoma.
AB  - BACKGROUND: Cisplatin (CDDP) ototoxicity is a significant side effect of the
      current treatment of medulloblastoma (MB). Cumulative dose of CDDP and age are
      recognized risk factors for hearing loss, but inter-individual susceptibility
      limits our ability to identify patients at risk for hearing loss. We describe the
      kinetics of early audiometric changes during therapy and identify profiles
      associated with a higher risk of needing hearing aids. PROCEDURE: Serial
      audiometric evaluations were performed during and after completion of therapy in
      children with average risk (AR) and high-risk (HR) MB. Each audiogram was scored
      according to five grading systems. Variations of pure tone thresholds were
      analyzed at each frequency for each consecutive audiogram. CDDP dose
      modifications and hearing outcome were recorded. RESULTS: A total of 258
      audiograms from 35 patients (22 AR, 13 HR) were analyzed. Eighteen AR patients
      (81.3%) required dose reduction and the median cumulative dose of CDDP
      administered was 412.5 mg/m(2) (150-600), corresponding to 68% of the intended
      dose. Three HR patients (23.0%) required dose reduction. At a median follow-up of
      67 months (11-117), nine patients (25.7%) required hearing support: After two
      cycles of CDDP (150 mg/m(2) ), the average hearing loss at 8,000 Hz was twice
      higher in the group that eventually required hearing support. CONCLUSION: Early
      alteration of high-frequency thresholds may help identify individuals who will
      require hearing support. In the MB population, alternative strategies should be
      developed to limit the cumulative dose of CDDP to prevent significant
      ototoxicity.

PMID- 23002031
TI  - Efficient protocol for isolation and purification of different soyasaponins from
      soy hypocotyls.
AB  - Soyasaponins are naturally occurring triterpenoid glycosides associated with many
      biological activities. The aim of the present study was to develop an effective
      method for isolation and purification of differently glycosylated, acetylated,
      and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated
      soyasaponins from soy hypocotyls. Both gel filtration using Sephadex LH-20
      chromatography (Amersham Pharmacia Biotech AB; elution phase: methanol, flow
      rate: 3.0 mL/min, sample loading: 60 mg) and high-speed countercurrent
      chromatography (stationary phase: n-butanol-acetic acid (5.0%, v/v), mobile
      phase: water flow rate: 3.0 mL/min, sample loading: 100 mg) could effectively
      fractionate isoflavones and soyasaponins from the crude extract with yield of
      soyasaponin complexes 20.5 mg and 22.3 mg, respectively. After fractionation, the
      soyasaponin complexes could be purified further using preparative HPLC to
      separate individuals. A total of nine soyasaponins, triacetyl soyasaponin Ab
      (yield 1.55%, HPLC purity >98%), Aa (2.68%, >99%), Ab (18.53%, >98%), Ae (0.85%,
      >98%), Ba (0.63%, >91%), Af (1.12%, >85%), Bb (3.45%, >98%) and Be (0.59%,
      >76.8%) were obtained. DDMP-conjugated groups, alphag (2.06%, >85%), betag
      (7.59%, >85%), and gammag (0.29%, >85%) that were very labile even in mild
      conditions, were also collected. The method described here can be used as an
      effective protocol to separate different soyasaponins occurring in the original
      sample.

PMID- 23002032
TI  - Diastolic dysfunction in rheumatoid arthritis: a meta-analysis and systematic
      review.
AB  - OBJECTIVE: To determine if the prevalence of diastolic dysfunction is increased
      in rheumatoid arthritis (RA) patients. METHODS: We conducted a time- and language
      restricted literature search to identify studies conducted to compare
      echocardiographic parameters in patients with RA and controls. The mean
      difference for echocardiographic variables of interest was calculated using a
      random-effects model. A systematic review of the literature was performed.
      RESULTS: A total of 25 studies reporting on 5,836 subjects (1,614 with RA) were
      included. Results reflect mean differences, with positive values denoting higher
      values in RA patients. Patients with RA had larger mean left atrial dimension
      (mean difference 0.09 cm [95% confidence interval (95% CI) 0.01, 0.17]; P =
      0.02), higher left ventricular mass index (mean difference 6.2 gm/m(2) [95% CI
      1.08, 11.33]; P = 0.02), higher mean systolic pulmonary artery pressure (mean
      difference 5.87 mm Hg [95% CI 4.36, 7.38]; P < 0.00001), prolonged isovolumetric
      relaxation time (mean difference 9.67 msec [95% CI 5.78, 13.56]; P < 0.00001),
      and higher transmitral A wave velocity (mean difference 0.13 meters/second [95%
      CI 0.07, 0.18]; P < 0.00001) compared to controls. A subanalysis of 2,183
      subjects excluding 2 large unmatched studies showed the same results, with the
      exception that patients with RA had a lower mitral E/A ratio (mean difference 
      0.17 [95% CI -0.25, -0.09]; P < 0.00001), suggestive of diastolic dysfunction.
      There were no differences in left ventricular ejection fraction (%), transmitral
      E wave velocity (meters/second), and mitral deceleration time (msec). CONCLUSION:
      Patients with RA were more likely to have echocardiographic parameters of
      diastolic dysfunction, and have higher systolic pulmonary artery pressures and
      larger left atrial sizes.

PMID- 23002033
TI  - Comparison of MRS and DWI in the diagnosis of prostate cancer based on sextant
      analysis.
AB  - PURPOSE: To evaluate apparent diffusion coefficient (ADC) value, metabolic ratio
      ((Cho + Cr)/Cit) and the combination of the two in identifying prostate malignant
      regions. MATERIALS AND METHODS: Fifty-six consecutive patients with prostate
      biopsy results were retrospectively recruited in this study. Transrectal
      ultrasound-guided (TRUS) systemic prostate biopsies were used as a standard of
      reference. Mean ADC value and mean metabolic ratio (MMR) were calculated within
      each benign sextant region or malignant region. The efficiency of these two
      indices in prostate cancer (PCa) diagnosis is estimated in Fisher linear
      discriminant analysis (FLDA). The area under the receiver operating
      characteristic (ROC) curve was used to evaluate the distinguishing capacity of
      mean ADC, MMR, and the combination of the two in differentiating between
      noncancerous and cancerous cases. RESULTS: There were significant differences for
      mean ADC value and MMR between malignant and benign regions. Weights of mean ADC
      value obtained by FLDA were much higher than those of MMR. In differentiating
      malignant regions, both ADC alone and combined ADC and metabolic ratio performed
      significantly better than MMR alone. However, accuracy improvements were not
      significant by using combined ADC and MMR than ADC alone. CONCLUSION: DWI is more
      efficient than MR spectroscopic (MRS) in the detection of PCa in this study.
      Combined ADC and MMR performed significantly better than MMR alone in
      distinguishing malignant from benign region in prostate peripheral zone.

PMID- 23002034
TI  - Blunted response to a growth hormone stimulation test is associated with
      unfavorable cardiovascular risk factor profile in childhood cancer survivors.
AB  - BACKGROUND: Childhood cancer survivors (CCS) are at risk for growth hormone (GH)
      deficiency. CCS are also at increased risk for early mortality from
      cardiovascular (CV) disease, but the association between GH levels and CV risk
      remains poorly understood. The goal of this study was to examine the cross
      sectional association between stimulated GH levels and CV risk factors in CCS
      younger than 18 years. PROCEDURE: A total of 276 CCS (147 males, 14.4 +/- 2.6
      years) >=5 years after cancer diagnosis, and 208 sibling controls (112 males,
      13.6 +/- 2.4 years) participated in this cross-sectional study, which included
      anthropometry, body composition, and metabolic studies. Blunted response (BR) was
      defined as peak GH level <7 ug/L after clonidine and arginine. Insulin
      sensitivity (M(lbm) ) was measured by euglycemic hyperinsulinemic clamp.
      Statistical analyses used linear and logistic regression accounting for sibling
      clustering, adjusted for age, sex, Tanner stage, and adiposity. RESULTS: Thirty
      four (12%) CCS showed BR to GH stimulation. BR CCS were shorter and had a lower
      IGF-1 than controls; only 6 of 34 received cranial radiation therapy. CCS with
      normal stimulated GH response were similar to controls for CV risk factors.
      Conversely, BR CCS had greater adiposity, higher lipids, and lower M(lbm) than
      controls. Differences in lipids and M(lbm) between BR CCS and controls remained
      significant after adjustment for BMI or visceral fat. CONCLUSIONS: BR to GH
      stimulation is prevalent in CCS youth and is associated with an unfavorable CV
      risk factor profile. Further studies are needed to establish the mechanisms of
      these associations.

PMID- 23002035
TI  - Muscle-specific vascular endothelial growth factor deletion induces muscle
      capillary rarefaction creating muscle insulin resistance.
AB  - Muscle insulin resistance is associated with a reduction in vascular endothelial
      growth factor (VEGF) action and muscle capillary density. We tested the
      hypothesis that muscle capillary rarefaction critically contributes to the
      etiology of muscle insulin resistance in chow-fed mice with skeletal and cardiac
      muscle VEGF deletion (mVEGF(-/-)) and wild-type littermates (mVEGF(+/+)) on a
      C57BL/6 background. The mVEGF(-/-) mice had an ~60% and ~50% decrease in
      capillaries in skeletal and cardiac muscle, respectively. The mVEGF(-/-) mice had
      augmented fasting glucose turnover. Insulin-stimulated whole-body glucose
      disappearance was blunted in mVEGF(-/-) mice. The reduced peripheral glucose
      utilization during insulin stimulation was due to diminished in vivo cardiac and
      skeletal muscle insulin action and signaling. The decreased insulin-stimulated
      muscle glucose uptake was independent of defects in insulin action at the
      myocyte, suggesting that the impairment in insulin-stimulated muscle glucose
      uptake was due to poor muscle perfusion. The deletion of VEGF in cardiac muscle
      did not affect cardiac output. These studies emphasize the importance for novel
      therapeutic approaches that target the vasculature in the treatment of insulin
      resistant muscle.

PMID- 23002036
TI  - Resistin knockout mice exhibit impaired adipocyte glucose-dependent
      insulinotropic polypeptide receptor (GIPR) expression.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that
      also plays a regulatory role in fat metabolism. In 3T3-L1 cells, resistin was
      demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL)
      activity, involving activation of protein kinase B (PKB) and reduced
      phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase
      (AMPK). The current study was initiated to determine whether resistin has
      additional roles in GIP-regulated adipocyte functions. Analysis of primary
      adipocytes isolated from Retn(-/-), Retn(+/-), and Retn(+/+) mice found that GIP
      stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+)
      adipocytes, suggesting that GIP signaling and/or GIP responsiveness were
      compromised in Retn(+/-) and Retn(-/-) adipocytes. GIP receptor (GIPR) protein
      and mRNA were decreased in Retn(+/-) and Retn(-/-) adipocytes, but resistin
      treatment rescued LPL responsiveness to GIP. In addition, genes encoding tumor
      necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress
      activated protein kinase (SAPK)/Jun NH(2)-terminal kinase (JNK), were
      downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in
      Retn(-/-) mice. Chromatin immunoprecipitation assays were used to identify a 12-O
      tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for
      c-Jun-mediated transcriptional activation of Gipr. Blunted GIP responsiveness in
      Retn(+/-) and Retn(-/-) adipocytes was therefore largely due to the greatly
      reduced GIPR expression associated with decreased c-Jun-mediated transcriptional
      activation of Gipr.

PMID- 23002037
TI  - Corneal confocal microscopy detects early nerve regeneration in diabetic
      neuropathy after simultaneous pancreas and kidney transplantation.
AB  - Diabetic neuropathy is associated with increased morbidity and mortality. To
      date, limited data in subjects with impaired glucose tolerance and diabetes
      demonstrate nerve fiber repair after intervention. This may reflect a lack of
      efficacy of the interventions but may also reflect difficulty of the tests
      currently deployed to adequately assess nerve fiber repair, particularly in short
      term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive
      means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients
      undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed
      assessment of neurologic deficits, quantitative sensory testing (QST),
      electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6
      and 12 months after successful SPK. At baseline, diabetic patients had a
      significant neuropathy compared with control subjects. After successful SPK there
      was no significant change in neurologic impairment, neurophysiology, QST, corneal
      sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM
      demonstrated significant improvements in corneal nerve fiber density, branch
      density, and length at 12 months. Normalization of glycemia after SPK shows no
      significant improvement in neuropathy assessed by the neurologic deficits, QST,
      electrophysiology, and IENFD. However, CCM shows a significant improvement in
      nerve morphology, providing a novel noninvasive means to establish early nerve
      repair that is missed by currently advocated assessment techniques.

PMID- 23002038
TI  - Autoimmunoreactive IgGs from patients with postural orthostatic tachycardia
      syndrome.
AB  - PURPOSE: Autoantibodies are implicated in the pathogenesis of cardiovascular
      diseases and cardiac arrhythmias. In this pilot study, we tested the hypothesis
      that autoantibodies are present in patients with postural orthostatic tachycardia
      syndrome (POTS). EXPERIMENTAL DESIGN: Seven control subjects (6 F:1 M, average
      age 36.1 years) and ten patients with the diagnosis of POTS (7 F: 3 M, average
      age 35.1 years) provided informed consent and 30 mL of venous blood. Human heart
      membrane proteins were resolved by 2DE and immunoblotted against purified IgGs
      from controls and patients. RESULTS: Eighteen protein spots immunoreactive
      specifically against patient IgGs were detected and they were excised from gels,
      trypsin-digested, and analyzed by nanoLC-electrospray MS/MS. Forty unique
      proteins were identified and these include proteins that are associated with
      cardiac hypertrophy (mimecan, myozenin), cardiac remodeling (periostin),
      cardiomyopathy (desmin, desmoplakin), cell survival (laminin), structural
      integrity (filamin), chaperone proteins (crystalline, HSP70), mitochondrial
      enzymes, and channel proteins. Ingenuity Pathway Analysis showed multiple
      pathways were involved including those that regulate energy metabolism, redox,
      fibrosis, cardiac hypertrophy, and degeneration. CONCLUSIONS AND CLINICAL
      RELEVANCE: Autoantibodies are present in patients with POTS. These autoantibodies
      cross-react with a wide range of cardiac proteins and may induce alterations in
      cardiac function. Autoimmune pathogenetic mechanisms should be further explored
      in these patients.

PMID- 23002039
TI  - A phase-1 pharmacokinetic optimal dosing study of intraventricular topotecan for
      children with neoplastic meningitis: a Pediatric Brain Tumor Consortium study.
AB  - PURPOSE: We performed a phase-1 pharmacokinetic optimal dosing study of
      intraventricular topotecan (IT), administered daily 5*, to determine whether, the
      maximum tolerated dose of IT topotecan was also the pharmacokinetic optimal dose.
      PATIENTS AND METHODS: Patients received topotecan administered through an
      intraventricular access device (0.1 or 0.2 mg/dose), daily * 5 every other week
      2* (Induction); every 3 weeks * 2 (Consolidation); then every 4 weeks for up to
      11 courses (Maintenance). Ventricular CSF pharmacokinetic studies were performed
      on day 1, week 1 of induction, and in a subset of patients after a single
      intralumbar topotecan dose on day 1, week 3. RESULTS: Nineteen patients were
      enrolled. All were evaluable for toxicity and 18 were assessable for
      pharmacokinetics. Arachnoiditis requiring corticosteroid therapy occurred in or
      one of three patients at the 0.1 mg dose level and two of the initial three
      patients enrolled at the 0.2 mg dose level. All subsequent patients were
      therefore treated with concomitant dexamethasone. Pharmacokinetic evaluation
      after accrual of the first seven patients revealed that a topotecan lactone
      concentration >1 ng/ml for 8 hours was attained in all patients and thus, further
      dose escalation was not pursued. Results of simulation studies showed that at the
      dose levels evaluated, >99.9% of patients are expected to achieve CSF topotecan
      lactone concentrations >1 ng/ml for at least 8 hours. CONCLUSION:
      Intraventricular topotecan, 0.2 mg, administered daily for 5 days with
      concomitant dexamethasone is well tolerated and was defined to be the
      pharmacokinetic optimal dose in this trial.

PMID- 23002040
TI  - The thyrotropin receptor hinge region as a surrogate ligand: identification of
      loci contributing to the coupling of thyrotropin binding and receptor activation.
AB  - The TSH receptor (TSHR) hinge region, the least well understood component,
      bridges the leucine-rich repeat and transmembrane domains. We report data on
      clusters of hinge charged residues the mutation of which to Ala is compatible
      with cell surface expression and normal, or near normal, TSH binding affinity yet
      with a relative reduction in receptor activation. Mutation to Ala of E409 at the
      junction with the transmembrane domain was the most potent in uncoupling TSH
      binding and signal transduction (~22-fold less sensitive than the wild-type TSHR)
      and was unique among the residues studied in reducing both the amplitude and the
      sensitivity of the ligand-induced signal. Unexpectedly, a dual E409A/D410A
      mutation partially corrected the major suppressive effect of TSHR-E409A. The
      combined Ala substitution of a cluster of positively charged hinge residues
      (K287, K290, K291, R293; termed "K3R1") synergistically reduced sensitivity to
      TSH stimulation approximately 21-fold without altering the TSH binding affinity.
      Simultaneous Ala substitutions of a cluster of acidic hinge residues D392, E394,
      and D395 (termed "DE392-5A") partially uncoupled TSH binding from signal
      transduction (4.4-fold reduction in sensitivity), less than for E409A and K3R1A.
      Remarkably, the combination of the K3R1A and DE392-5A mutations was not additive
      but ameliorated the major uncoupling effect of K3R1A. This lack of additivity
      suggests that these two clusters contribute to a common signaling pathway. In
      summary, we identify several TSHR hinge residues involved in signal transmission.
      Our data support the concept that the hinge regions of the TSHR (and other
      glycoprotein hormone receptors) act as surrogate ligands for receptor activation.

PMID- 23002041
TI  - Distinguishing benign from malignant mesothelial cells in effusions by Glut-1,
      EMA, and Desmin expression: an evidence-based approach.
AB  - Distinguishing malignant mesothelioma (MM) from reactive mesothelial hyperplasia
      (RM) may be difficult in effusions. This study tested the hypothesis that
      immunocytochemistry (IC) in effusion cell blocks (CB) can distinguish MM from RM
      and that the results may be applied to individual specimens. External validation
      of a risk score (RS) model associating sensitivity and specificity was applied to
      an external set of MM and RM specimens from a separate institution. Forty three
      effusion cytology CBs of 25 confirmed malignant mesotheliomas were compared to
      CBs of 23 benign mesothelial effusions without inflammation and 13 reactive
      mesothelial proliferations associated with inflammation. Glut-1, EMA, and Desmin
      expression were evaluated by immunocytochemistry on CBs. Each antibody was
      compared using ROC values, where the area under the curve (AUC) was 0.90, 0.82,
      and 0.84 for Glut-1, EMA, and Desmin, respectively. Logistic regression (LR)
      analysis was applied to a combination of Glut-1 and EMA. A combined ROC curve was
      modeled for Glut-1 and EMA (AUC = 0.93). A RS = 2 * (Glut-1%) + 1 * (EMA%) was
      created from this ROC curve. When applied to an external set of MM and RM, the RS
      resulted in an ROC with AUC = 0.91. In conclusion, a RS derived from a LR of Glut
      1 and EMA IC greatly improves the distinction between MM from RM cells in
      individual effusions. The study illustrates principles of evidence-based
      pathology concerning internal and external test performance in the differential
      diagnosis of MM versus RM.

PMID- 23002042
TI  - Glatiramer acetate ameliorates inflammatory bowel disease in mice through the
      induction of Qa-1-restricted CD8+ regulatory cells.
AB  - Inflammatory bowel diseases (IBDs) are complex multifactorial immunological
      disorders characterized by dysregulated immune reactivity in the intestine. Here,
      we investigated the contribution of Qa-1-restricted CD8(+)  Treg cells in
      regulating experimental IBD in mice. We found that CD8(+)  T cells induced by T
      cell vaccination ameliorated the pathological manifestations of dextran sulfate
      sodium induced IBD when adoptively transferred into IBD mice. In addition, CD8(+)
      cell suppressive activity was induced by vaccination with glatiramer acetate
      (GA), an FDA-approved drug for multiple sclerosis (MS). We next showed that GA
      induced CD8(+)  Treg cells worked in a Qa-1-dependent manner and their
      suppressive activity depends on perforin-mediated cytotoxicity. Finally, we
      confirmed the role of CD4(+)  T cells in dextran sulfate sodium induced colitis
      progression, and clarified that GA-induced CD8(+)  T cells exerted their
      therapeutic effects on colitis by targeting pathogenic CD4(+)  T cells. Our
      results reveal a new regulatory role of Qa-1-restricted CD8(+)  Treg cells in IBD
      and suggest their induction by GA vaccination as a potential therapeutic approach
      to IBD.

PMID- 23002043
TI  - Reliability of ambulatory urodynamics in patients with spinal cord injuries.
AB  - OBJECTIVE: To determine the test-retest repeatability of the urodynamic
      parameters commonly utilized in ambulatory urodynamics (AM) for patients with
      neurogenic lower urinary tract dysfunction (NLUTD). METHODS: A test-retest
      repeatability study was performed on 64 consecutive patients with stable spinal
      cord injuries who underwent two AM studies 24 hr apart. RESULTS: The mean age was
      43.2 years, with 47 males and 17 females. A significant intraclass correlation
      coefficient (ICC) was found between the two studies with respect to the
      functional bladder capacity (FBC; 0.74), the maximum detrusor pressure during the
      involuntary detrusor contraction (P(detmaxIDC); 0.84), and the post-void residual
      (PVR; 0.76). Of note, the ICC of the end filling detrusor pressure (P(detfill))
      was not significant (0.25). The correlation with respect to the presence of
      involuntary detrusor contraction (IDC) was significant but low (kappa = 0.40).
      Based on the logistic regression analysis, the variables that influenced the
      concordance with respect to the presence of the IDC were P(detmaxIDC) (directly)
      and P(detmax) (inversely). The variable that that influenced the concordance with
      respect to P(detmaxIDC) was PVR (directly). The variable that influenced the
      concordance with respect to PVR was the FBC (directly). CONCLUSIONS: AM is
      reliable for the reproduction of the main urodynamic parameters investigated in
      patients with NLUTD, except for the end filling detrusor pressure, which was a
      non-reliable parameter. The concordance of AM can be improved primarily by taking
      into account the values of the maximum detrusor pressure during involuntary
      detrusor contraction (P(detmaxIDC)).

PMID- 23002044
TI  - Lactobacillus shenzhenensis sp. nov., isolated from a fermented dairy beverage.
AB  - Two Lactobacillus strains, designated LY-73(T) and LY-30B, were isolated from a
      dairy beverage, sold in Shenzhen market, China. The two isolates were Gram
      positive, non-spore-forming, non-motile, facultatively anaerobic rods that were
      heterofermentative and did not exhibit catalase activity. Sequencing of the 16S
      rRNA, pheS and rpoA genes revealed that the two isolates shared 99.5, 99.8 and
      99.9 % sequence similarity, which indicates that they belong to the same species.
      Phylogenetic analysis demonstrated clustering of the two isolates with the genus
      Lactobacillus. Strain LY-73(T) showed highest 16S rRNA gene sequence similarities
      with Lactobacillus harbinensis KACC 12409(T) (97.73%), Lactobacillus perolens DSM
      12744(T) (96.96 %) and Lactobacillus selangorensis DSM 13344(T) (93.10 %).
      Comparative analyses of their rpoA and pheS gene sequences indicated that the
      novel strains were significantly different from other Lactobacillus species. Low
      DNA-DNA reassociation values (50.5 %) were obtained between strain LY-73(T) and
      its phylogenetically closest neighbours. The G+C contents of the DNA of the two
      novel isolates were 56.1 and 56.5 mol%. Straight-chain unsaturated fatty acids
      C18 : 1omega9c (78.85 and 74.29 %) were the dominant components, and the cell
      wall peptidoglycan was of the l-Lys-d-Asp type. Based on phenotypic
      characteristics, and chemotaxonomic and genotypic data, the novel strains
      represent a novel species of the genus Lactobacillus, for which the name
      Lactobacillus shenzhenensis sp. nov. is proposed, with LY-73(T) ( = CCTCC M
      2011481(T) = KACC 16878(T)) as the type strain.

PMID- 23002045
TI  - Pseudomonas punonensis sp. nov., isolated from straw.
AB  - During a study of the 'tunta' (frozen-dry potato) production process in Peru, a
      bacterial strain, LMT03(T), was isolated from the straw grass in which the
      potatoes are dried. This strain was classified into the genus Pseudomonas on the
      basis of the 16S rRNA gene sequence analysis, and is most closely related to
      Pseudomonas argentinensis CH01(T) with 99.3 % identity in this gene and 96 %, 92
      % and 86 % identities in rpoB, rpoD and gyrB genes, respectively. Strain LMT03(T)
      has a single polar flagellum, like other related yellow-pigment-producing
      pseudomonads. The major quinone is Q-9. The major fatty acids are C18 : 1omega7c
      in summed feature 8 (40.82 %), C16 : 1omega6c/C16 : 1omega6c in summed feature 3
      (23.72 %) and C16 : 0 (15.20 %). The strain produces oxidase but it does not
      produce gelatinase, indole, urease, arginine dihydrolase or beta-galactosidase.
      Catalase production was very weak after 28 and 48 h incubation on nutrient agar
      medium. Nitrate reduction is negative. It does not hydrolyse aesculin. The DNA
      G+C content is 57.8 mol%. DNA-DNA hybridization results showed lower than 52 %
      relatedness with respect to the type strain of P. argentinensis, CH01(T). These
      results, together with other phenotypic characteristics, support the definition
      of a novel species within the genus Pseudomonas, for which the name Pseudomonas
      punonensis sp. nov. is proposed. The type strain is LMT03(T) ( = LMG 26839(T) =
      CECT 8089(T)).

PMID- 23002046
TI  - Flaviflexus huanghaiensis gen. nov., sp. nov., an actinobacterium of the family
      Actinomycetaceae.
AB  - Strain H5(T) was isolated from a sediment sample collected from the coastal area
      of Qingdao, China. The cells were Gram-stain-positive, non-motile, straight or
      curved rods. The temperature range for growth was 20-37  degrees C and the pH for
      growth ranged from 6.5 to 9.0, with optimum growth occurring in the temperature
      range 28-30  degrees C and pH range 7.5-8.0. Growth occurred in the presence of 0
      6% (w/v) NaCl (optimum, 0-2%). Strain H5(T) had MK-9, MK-9(H2) and MK-9(H4) as
      the major menaquinones and C18:1omega9c, C16:0, C14:0, C18:0 and C16:1omega9c as
      major fatty acids. The cell-wall peptidoglycan type was A5alpha l-Lys-l-Ala-l-Lys
      d-Glu. The major polar lipids were phosphatidylglycerol (PG), an unknown
      phospholipid (PL1) and two unknown phosphoglycolipids (PGL1, PGL2). An unknown
      phospholipid (PL2) and two unknown glycolipids (GL1, GL2) were present in
      moderate to minor amounts in the polar lipid profile. The genomic DNA G+C content
      was 61.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that
      strain H5(T) represents a novel lineage in the family Actinomycetaceae. On the
      basis of phenotypic, physiological and molecular characteristics, it is proposed
      that the novel isolate should be classified as a novel species in a new genus:
      Flaviflexus huanghaiensis gen. nov., sp. nov., with strain H5(T) ( = DSM 24315(T)
      =CICC 10486(T)) as the type strain of the type species.

PMID- 23002047
TI  - Aureicoccus marinus gen. nov., sp. nov., a member of the family
      Flavobacteriaceae, isolated from seawater.
AB  - A coccoid and amorphous-shaped, non-gliding, proteorhodopsin-containing, yellow
      bacterium, designated strain SG-18(T), was isolated from seawater in the western
      North Pacific Ocean near Japan. The strain was Gram-stain-negative, obligately
      aerobic, heterotrophic and oxidase-positive. It hydrolysed aesculin but not DNA,
      urea, gelatin or agar. Growth occurred in the presence of 1-5 % NaCl, with
      optimum growth at 2 % NaCl. The strain grew at 15-37  degrees C with an optimum
      temperature of 25-30  degrees C. The DNA G+C content of the genomic DNA of strain
      SG-18(T) was 47.0 mol% (HPLC). The predominant isoprenoid quinone was MK-6, and
      major cellular fatty acids were iso-C15 : 1 G, iso-C15 : 0, iso-C15 : 0 3-OH.
      Phylogenetic trees generated by using 16S rRNA gene sequences revealed that
      strain SG-18(T) belonged to the family Flavobacteriaceae and showed 92.7 %
      sequence similarity to the most closely related species, Croceitalea eckloniae
      DOKDO 025(T). On the basis of phenotypic and phylogenetic features, strain SG
      18(T) is classified as representing a novel species of a new genus within the
      family Flavobacteriaceae, for which the name Aureicoccus marinus gen. nov., sp.
      nov. is proposed. The type strain of the type species is SG-18(T) ( = NBRC
      108814(T) = KCTC 23967(T)).

PMID- 23002048
TI  - Luteolibacter yonseiensis sp. nov., isolated from activated sludge using algal
      metabolites.
AB  - A Gram-negative, rod-shaped, aerobic bacterial strain, designated EBTL01(T), was
      isolated from activated sludge by using metabolites of microalgae Ankistrodesmus
      gracilis SAG278-2. Phylogenetic analyses based on 16S rRNA gene sequence showed
      that strain EBTL01(T) belongs to the family Verrucomicrobiaceae, class
      Verrucomicrobiae, and is related most closely to Luteolibacter pohnpeiensis A4T
      83(T) (95.5 % sequence similarity) and Luteolibacter algae A5J-41-2(T) (95.2 %).
      The G+C content of the genomic DNA of strain EBTL01(T) was 56.3 mol% and the
      menaquinone MK-9 was detected as the predominant quinone. Major fatty acid
      components were iso-C14 : 0, C16 : 1omega7c and C16 : 0. The amino acids of the
      cell-wall peptidoglycan contained muramic acid and meso-diaminopimelic acid.
      These profile results supported the affiliation of strain EBTL01(T) to the genus
      Luteolibacter. On the other hand, based on chemotaxonomic properties and
      phenotypic characteristics, strain EBTL01(T) could be clearly differentiated from
      its phylogenetic neighbours. Therefore, strain EBTL01(T) represents a novel
      species of the genus Luteolibacter, for which the name Luteolibacter yonseiensis
      sp. nov. is proposed. The type strain is EBTL01(T) ( = KCTC 23678(T) = JCM
      18052(T)).

PMID- 23002049
TI  - Actinoallomurus acanthiterrae sp. nov., an actinomycete isolated from rhizosphere
      soil of the mangrove plant Acanthus ilicifolius.
AB  - A novel actinobacterium strain, 2614A723(T), was isolated from rhizosphere soil
      of mangrove plant Acanthus ilicifolius collected at Touyuan, Wenchang, Hainan
      province, China. A phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain 2614A723(T) formed a distinct phyletic line in the genus
      Actinoallomurus, the 16S rRNA gene tree sharing similarities of 98.35%, 98.07%
      and 97.86% with Actinoallomurus spadix NBRC 14099(T), Actinoallomurus purpureus
      TTN02-30(T) and Actinoallomurus luridus TT02-15(T), respectively. Strain
      2614A723(T) contained lysine and meso-diaminopimelic acid in the cell wall
      peptidoglycan and madurose, galactose and xylose in the whole-cell sugars. The
      predominant menaquinones were MK-9(H4) and MK-9(H6). The major polar
      phospholipids were phosphatidylglycerol and diphosphatidylglycerol. The
      predominant fatty acids were iso-C16 : 0 and anteiso-C17 : 0. These
      chemotaxonomic data confirmed the affiliation of strain 2614A723(T) to the genus
      Actinoallomurus. It is apparent from the combined phenotypic data, biochemical
      tests and DNA-DNA hybridization values that strain 2614A723(T) should be
      classified in the genus Actinoallomurus as a representative of a novel species.
      The name Actinoallomurus acanthiterrae sp. nov. is proposed with strain
      2614A723(T) ( = CCTCC AA 2012001(T) = DSM 45727(T)) as the type strain.

PMID- 23002050
TI  - Eilatimonas milleporae gen. nov., sp. nov., a marine bacterium isolated from the
      hydrocoral Millepora dichotoma.
AB  - A marine bacterial strain, designated MD2(T), was isolated from the damaged
      tissue of a hydrocoral, Millepora dichotoma, collected from the coral reef in the
      northern Red Sea, Gulf of Eilat, Israel. Strain MD2(T) was Gram-reaction
      negative, rod-shaped and motile, and formed small, creamy and opaque colonies, 1
      2 mm in diameter, after 3 days incubation on Marine agar at 30 degrees C. The
      novel strain grew well in nutrient broth at 1.5-6 % NaCl and at 20-37 degrees C.
      The major cellular fatty acids were iso-C17 : 1omega9c, iso-C17 : 0, C18 :
      1omega7c and C17 : 1omega6c. The polar lipids consisted of phosphatidylglycerol,
      phosphatidylethanolamine, an unidentified lipid, two unidentified phospholipids,
      two unidentified glycolipids and two unidentified aminolipids. Ubiquinone Q-10
      was the only respiratory lipoquinone. The DNA G+C content was 60.3 mol%. Analysis
      of the 16S rRNA gene sequence placed the organism in the alpha-subclass of the
      Proteobacteria with a sequence divergence of about 9 % from any species with a
      validly published name. The highest 16S rRNA gene sequence similarity
      (approximately 91 %) was notably with type strains of members of the genus
      Kordiimonas, Kordiimonas aestuarii 101-1(T), Kordiimonas lacus S3-22(T) and
      Kordiimonas gwangyangensis GW14-5(T). On the basis of genotypic, chemotaxonomic
      and phenotypic distinctness, strain MD2(T) represents a novel species in a new
      genus of the class Alphaproteobacteria, for which the name Eilatimonas milleporae
      gen. nov., sp. nov. is proposed. The type strain of the type species is MD2(T) (
      = LMG 26586(T) = DSM 25217(T)).

PMID- 23002051
TI  - Streptomyces chiangmaiensis sp. nov. and Streptomyces lannensis sp. nov.,
      isolated from the South-East Asian stingless bee (Tetragonilla collina).
AB  - Two novel actinomycetes, strains TA4-1(T) and TA4-8(T,) were isolated from the
      South-East Asian stingless bee (Tetragonilla collina Smith 1857), collected from
      Chiang Mai Province, Thailand. The morphological and chemotaxonomic properties of
      strains TA4-1(T) and TA4-8(T) were consistent with the genus Streptomyces, i.e.
      the formation of aerial mycelia bearing spiral spore chains, the presence of the
      ll-isomer of diaminopimelic acid in cell walls, iso- and anteiso-branched fatty
      acids with carbon chain lengths 14-17 atoms as the major fatty acids and MK-9(H8)
      as the predominant menaquinone plus minor amounts of MK-9(H6) and MK-9(H10).
      Analysis of 16S rRNA gene sequences showed that strains TA4-1(T) and TA4-8(T)
      exhibited 98.8 and 98.1% sequence similarity, respectively, with Streptomyces
      chromofuscus NRRL B-12175(T) and 98.9% sequence similarity with each other. This
      study suggested that strains TA4-1(T) and TA4-8(T) were distinct from previously
      described species of the genus Streptomyces. In addition, the low degrees of DNA
      DNA relatedness between the isolates and S. chromofuscus JCM 4354(T) warranted
      assigning strains TA4-1(T) and TA4-8(T) to two novel species. The names
      Streptomyces chiangmaiensis sp. nov. (type strain TA4-1(T)  = JCM 16577(T)  =
      TISTR 1981(T)) and Streptomyces lannensis sp. nov. (type strain TA4-8(T)  = JCM
      16578(T)  = TISTR 1982(T)) are proposed. The species names indicate the
      geographical locations where the stingless bees reside.

PMID- 23002052
TI  - Endobacter medicaginis gen. nov., sp. nov., isolated from alfalfa nodules in an
      acidic soil.
AB  - A bacterial strain designated M1MS02(T) was isolated from a surface-sterilized
      nodule of Medicago sativa in Zamora (Spain). The 16S rRNA gene sequence of this
      strain showed 96.5 and 96.2 % similarity, respectively, with respect to
      Gluconacetobacter liquefaciens IFO 12388(T) and Granulibacter bethesdensis
      CGDNIH1(T) from the family Acetobacteraceae. The novel isolate was a Gram-stain
      negative, non-sporulating, aerobic coccoid to rod-shaped bacterium that was
      motile by a subpolar flagellum. The major fatty acid was C18 : 1omega7c and the
      major ubiquinone was Q-10. The lipid profile consisted of diphosphatidylglycerol,
      phosphatidylethanolamine, two aminophospholipids, three aminolipids, four
      glycolipids, two phospholipids and one lipid. Strain M1MS02(T) was catalase
      positive and oxidase- and urease-negative. Acetate and lactate were not oxidized.
      Acetic acid was produced from ethanol in culture media supplemented with 2 %
      CaCO3. Ammonium sulphate was assimilated in glucose medium. The strain produced
      dihydroxyacetone from glycerol. Phylogenetic and phenotypic analyses commonly
      used to differentiate genera within the family Acetobacteraceae showed that
      strain M1MS02(T) should be classified as representing a novel species of a new
      genus within this family, for which the name Endobacter medicaginis gen. nov.,
      sp. nov. is proposed. The type strain of the type species is M1MS02(T) ( = LMG
      26838(T) = CECT 8088(T)). To our knowledge, this is the first report of a member
      of the Acetobacteraceae occurring as a legume nodule endophyte.

PMID- 23002053
TI  - Remarkable temporal stability of high-abundance human plasma proteins assessed by
      targeted mass spectrometry.
AB  - PURPOSE: To examine temporal fluctuations in selected plasma protein levels over
      a period of nearly 4 months and assess biological variation of these proteins
      across a healthy population cohort. EXPERIMENTAL DESIGN: Plasma was collected
      from ten healthy volunteers over two time-courses: (i) weekly for 4 weeks; (ii)
      bimonthly over 4 months and depleted of albumin and IgG. SRM MS was used to
      determine the relative quantitation of 31 plasma proteins commonly observed in
      biomarker studies over these time courses. Estimates of between-subject and
      within-subject biological variances determined by SRM were calculated for each
      protein. RESULTS: Replicate analysis demonstrated the high precision of SRM
      assays of plasma proteins. Statistical analysis indicated that none of the
      measured proteins exhibited significant temporal fluctuations over either time
      course. Overall, time-based intraindividual quantitative variation of plasma
      protein levels was considerably lower than biological variation occurring between
      individual volunteers. CONCLUSIONS AND CLINICAL RELEVANCE: This study is the
      first to show robust temporal stability of the plasma proteome in healthy
      individuals using SRM-based peptide quantitation. This is important as it
      provides a strong basis for reliable detection of disease/treatment-related
      changes of these plasma proteins and others using SRM.

PMID- 23002054
TI  - Effectiveness of pamidronate as treatment of symptomatic osteonecrosis occurring
      in children treated for acute lymphoblastic leukemia.
AB  - BACKGROUND: Osteonecrosis (ON) is a severe complication of acute lymphoblastic
      leukemia (ALL) treatments. Recent studies suggest that bisphosphonates might
      reduce pain and loss of motor function in patients with ON. We assessed the
      effects of pamidronate compared to standard care in patients with symptomatic ON
      (sON) and studied whether steroids might be continued after diagnosis of ON in
      some patients. METHODS: We evaluated 17 patients with sON as complication of
      primary ALL treatment between 2000 and 2008. Fourteen patients were treated with
      pamidronate. Mobility and pain control were monitored in all patients. Affected
      joints were classified by magnetic resonance imaging (MRI) at ON diagnosis and
      after 6-72 months. RESULTS: Out of 220 patients with ALL, 17 (7.7%) patients
      developed sON. The median age at ALL diagnosis was 11 years (range: 2.7-16.6
      years) and sON occurred a median of 13.4 months (range: 2.5-34 months) after ALL
      diagnosis. Affected joints were hip, knee and ankle. MRI scans showed 7 severe, 4
      moderate, and 6 mild ON lesions. Fourteen patients showed improvement in pain
      (77% of patients) and motor function (59% of patients), even though corticoids
      were reintroduced in 4 patients. MRI demonstrated improvement, stability or
      worsening in 6, 3, and 5 cases, respectively. CONCLUSIONS: Pamidronate seems to
      be effective in the management of pain and motor function recovery in sON.
      Further studies are needed to provide evidence as to whether bisphosphonates can
      be recommended for the treatment or the prevention of ON in childhood ALL
      patients.

PMID- 23002055
TI  - Inflammatory and regulatory T cells contribute to a unique immune
      microenvironment in tumor tissue of colorectal cancer patients.
AB  - Colorectal cancer is one of the five leading causes of cancer mortality
      worldwide. The mechanisms of pathogen clearance, inflammation and regulation by T
      cells in the healthy bowel are also important in controlling tumor growth. The
      majority of studies analyzing T cells and their relationship to colorectal tumor
      growth have focused on individual T cell markers or gene clusters and thus the
      complexity of the T cell response contributing to the growth of the tumor is not
      clear. We have studied the T cells in colorectal cancer patients and have defined
      a unique T cell signature for colorectal tumor tissue. Using a novel analytical
      flow cytometric approach in concert with confocal microscopy, we have shown that
      the tumor has a lower frequency of effector T cells (CD69+), but a higher
      frequency of both regulatory (CD25hi Foxp3+) and inflammatory T cells (IL-17+)
      compared with associated nontransformed bowel tissue. We have also identified
      minor populations of T cells expressing conventional markers of both inflammatory
      and regulatory T cells (CD4+IL-17+Foxp3+) in the tumor tissue. These cells may
      represent intermediate populations or they may dictate an inflammatory versus
      regulatory function in surrounding T cells. Together, these data describe an
      immune microenvironment in colorectal cancer unique to the tumor tissue and
      distinct from the surrounding healthy bowel tissue, and this distinct environment
      is reflected by a gradient of T cells expressing markers of multiple T cell
      populations. These findings may be used to improve diagnosis and prognosis of
      colorectal cancer patients.

PMID- 23002056
TI  - Evolution of midurethral and other mesh slings--a critical analysis.
AB  - We analyzed our original experimental studies on which the midurethral sling was
      based with reference to FDA mesh warnings. We concluded that: 1. Vascular/organ
      damage could be avoided by first penetrating the urogenital diaphragm. 2. A non
      stretch tape minimizes obstruction and urethral damage. 3. A non-obstructive
      musculoelastic mechanism closes the urethra. 4. The strength of neocollagen
      (>92.8 lbs/sq inch) indicates that little mesh is required for prolapse repair.
      5. Foreign body (mesh) reaction is different from infection and is related to
      volume implanted. 6. Urgency is potentially curable by repairing the suspensory
      ligaments. 7. "Minislings" are promising for incontinence and POP, but more
      development is required.

PMID- 23002057
TI  - Mathematical modelling of cytokine-mediated inflammation in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease preferentially
      affecting the joints and leading, if untreated, to progressive joint damage and
      disability. Cytokines, a group of small inducible proteins, which act as
      intercellular messengers, are key regulators of the inflammation that
      characterizes RA. They can be classified into pro-inflammatory and anti
      inflammatory groups. Numerous cytokines have been implicated in the regulation of
      RA with complex up and down regulatory interactions. This paper considers a two
      variable model for the interactions between pro-inflammatory and anti
      inflammatory cytokines, and demonstrates that mathematical modelling may be used
      to investigate the involvement of cytokines in the disease process. The model
      displays a range of possible behaviours, such as bistability and oscillations,
      which are strongly reminiscent of the behaviour of RA e.g. genetic susceptibility
      and remitting-relapsing disease. We also show that the dose regimen as well as
      the dose level are important factors in RA treatments. 

PMID- 23002058
TI  - Brush border myosin Ia inactivation in gastric but not endometrial tumors.
AB  - Brush border Myosin Ia (MYO1A) has been shown to be frequently mutated in
      colorectal tumors with microsatellite instability (MSI) and to have tumor
      suppressor activity in intestinal tumors. Here, we investigated the frequency of
      frameshift mutations in the A8 microsatellite in exon 28 of MYO1A in MSI gastric
      and endometrial tumors and found a high mutation rate in gastric (22/47; 46.8%)
      but not endometrial (3/48; 6.2%) tumors. Using a regression model, we show that
      MYO1A mutations are likely to confer a growth advantage to gastric, but not
      endometrial tumors. The mutant MYO1A(7A)  protein was shown to lose its membrane
      localization in gastric cancer cells and a cycloheximide-chase assay demonstrated
      that the mutant MYO1A(7A)  protein has reduced stability compared to the wild
      type MYO1A. Frequent MYO1A promoter hypermethylation was also found in gastric
      tumors. Promoter methylation negatively correlates with MYO1A mRNA expression in
      a series of 58 non-MSI gastric primary tumors (Pearson's r = -0.46; p = 0.0003)
      but not in a cohort of 54 non-MSI endometrial tumors and treatment of gastric
      cancer cells showing high MYO1A promoter methylation with the demethylating agent
      5-aza-2'-deoxycytidine, resulted in a significant increase of MYO1A mRNA levels.
      We found that normal gastric epithelial cells, but not normal endometrial cells,
      express high levels of MYO1A. Therefore, when considered together, our findings
      suggest that MYO1A has tumor suppressor activity in the normal gastric epithelium
      but not in the normal endometrium and inactivation of MYO1A either genetically or
      epigenetically may confer gastric epithelial cells a growth advantage.

PMID- 23002060
TI  - Pacemakers in the upper urinary tract.
AB  - BACKGROUND: Pacemakers in upper urinary tract (UUT) are still under study. AIM:
      We reviewed the role of some cells that seem to be involved in the propulsion of
      urinary bolus from UUT to the bladder. MATERIALS & METHODS: We focuses on
      evaluating studies on the mechanisms by which the UUT propels urine to the
      bladder via pacemaker cells. RESULTS: Electric active pacemaker cells generate
      pyeloureteric autorhythmicity driving adjacent smooth muscle cells (SMCs); it
      emphasizes the role of the interstitial cells of Cajal-like cells (ICC-LCs)
      localized in the UUT. Interstitial cells of Cajal (ICCs) are now thought to
      cooperate in conducting and amplifying pacemaker activity in the UUT. These cells
      produce electrical slow-wave potentials and determine the propagation of
      peristaltic activity. Identification of ICC-LCs is facilitated by use of c-kit
      antibodies. Contraction waves arising from the UUT and the propagation of these
      waves may require the direct involvement of ICC-LCs, as c-kit immunoreactivity
      appears developmentally at the same time as coordinated unidirectional
      peristaltic contraction. ICC-LCs observed in the UUT have morphological features
      similar to those of c-kitpositive ICCs in the gastrointestinal tract. In addition
      to gastrointestinal motility, ICCs may also play a significant role in the
      propagation, coordination, and modulation of ureteropelvic peristalsis.
      DISCUSSION: Alterations in ICC-LCs are closely associated with a variety of
      motility disorders and many congenital urological diseases of the UUT such as
      primary obstructive megaureter, congenital ureteropelvic junction obstruction,
      and vesicoureteral reflux. CONCLUSION: These observations open the way for
      further investigations of this cell type.

PMID- 23002059
TI  - Objective and subjective assessments of nasal obstruction in children and
      adolescents with allergic rhinitis.
AB  - OBJECTIVE: To correlate objective assessment of nasal obstruction, as measured by
      acoustic rhinometry (volume of the first 5 cm of the nasal cavity) and active
      anterior rhinomanometry (total nasal airway resistance), with its subjective
      evaluation (obstruction scores). METHOD: Thirty patients, aged 7 to 18 years,
      with persistent allergic rhinitis and thirty controls were enrolled. The
      obstruction score was reported for the whole nasal cavity and for each nostril
      separately. The three variables were measured at baseline and after induction of
      nasal obstruction. RESULTS: There were significant and negative correlations
      between resistance and nasal volume in all groups and scenarios, except for the
      most obstructed nostril, in the control group, post-obstruction. For the whole
      nasal cavity, there was no significant correlation between objective and
      subjective variables except between score and total nasal cavity volume in the
      control group, post-obstruction. Regarding the most obstructed nostril, we found
      a significant negative correlation between score and resistance and a significant
      positive correlation between score and volume for the total group at baseline.
      There were no clear differences in the correlation coefficients found in patients
      and controls. The correlation coefficients did not change after induction of
      nasal obstruction. CONCLUSIONS: Objective assessment of nasal obstruction did not
      correlate significantly with subjective evaluation for the nasal cavity as a
      whole, but there was a correlation for unilateral assessments. There was
      correlation between the objective evaluations. Allergic rhinitis and acute
      induction of nasal obstruction did not affect the correlation between objective
      and subjective assessments of nasal obstruction. Addition of an objective method
      for evaluation of nasal obstruction could be useful in the research setting; if
      no such method can be used, each nostril should be evaluated separately.

PMID- 23002061
TI  - The nucleolus and herpesviral usurpation.
AB  - The nucleolus is a distinct subnuclear compartment known as the site for ribosome
      biogenesis in eukaryotes. Consequently, the nucleolus is also proposed to
      function in cell-cycle control, stress sensing and senescence, as well as in
      viral infection. An increasing number of viral proteins have been found to
      localize to the nucleolus. In this article, we review the current understanding
      of the functions of the nucleolus, the molecular mechanism of cellular and viral
      protein targeting to the nucleolus and the functional roles of the nucleolus
      during viral infection with a specific focus on the herpesvirus family.

PMID- 23002062
TI  - A bumpy road to the diagnosis of a Kytococcus schroeteri shunt infection.
AB  - We report a ventriculoperitoneal shunt infection associated with Kytococcus
      schroeteri, a Gram-positive bacterium from the family Dermacoccaceae. While the
      biochemical identification systems do not reliably identify this potential
      pathogen, sequence-based identification is recommended to guide the antibiotic
      treatment of this intrinsically meticillin-resistant species, which is
      susceptible to vancomycin, gentamicin and/or rifampicin.

PMID- 23002063
TI  - A severe case of Aeromonas veronii biovar sobria travellers' diarrhoea
      characterized by Vibrio parahaemolyticus co-isolation.
AB  - We report a severe case of travellers' diarrhoea in a patient returning from
      Ecuador to Italy with the concomitant presence of Aeromonas veronii biovar sobria
      and Vibrio parahaemolyticus in their faeces. Based on diagnostic results,
      epidemiological information and the clinical outcome, we conclude that the real
      aetiological agent was A. veronii biovar sobria, while V. parahaemolyticus was
      only transient in the intestine of the patient.

PMID- 23002064
TI  - Evaluation of antimicrobial activity against Mycoplasma mycoides subsp. mycoides
      Small Colony using an in vitro dynamic dilution pharmacokinetic/pharmacodynamic
      model.
AB  - The objectives of this study were to assess the activity of oxytetracycline
      (OTC), danofloxacin and tulathromycin against Mycoplasma mycoides subsp. mycoides
      Small Colony, the causative agent of contagious bovine pleuropneumonia, in an in
      vitro dynamic concentration model and to determine the concentration and/or time
      dependence of such activity. Time-kill assays that simulated elimination of
      antimicrobials from the body were performed. Initial antimicrobial concentrations
      corresponded to various multiples of the MIC and cultures were diluted in a
      stepwise fashion with either drug-free or drug-containing artificial medium to
      mimic administration by single-release bolus or infusion, respectively. Where
      appropriate, data were fitted to sigmoidal E(max) models. OTC produced no change
      in mycoplasma titre from the initial inoculum size, regardless of the
      concentration or means of drug exposure. Both danofloxacin and tulathromycin
      resulted in a decrease in mycoplasma titre but neither was bactericidal (99.9 %
      kill) over 12 h. A greater antimycoplasmal effect, defined as the change in
      log(10) (c.f.u. ml(-1)) over 12 h, was achieved when danofloxacin was
      administered as a single-release bolus, suggesting concentration-dependent
      activity, whereas the antimycoplasmal effect of tulathromycin was comparable
      following administration by single-release bolus or infusion, owing to its long
      half-life.

PMID- 23002065
TI  - Fluconazole resistance in Candida glabrata is associated with increased bud
      formation and metallothionein production.
AB  - Virulence associated with fluconazole (FL) resistance in Candida glabrata is a
      global problem and has not been well characterized at the proteome level. In this
      study, a stable FL-resistant (MIC >256 ug ml(-1)) strain of C. glabrata was
      generated on agar containing FL. Eight phenotypic mutants were characterized by
      contour-clamped homogeneous electrophoretic field analysis and two-dimensional
      PAGE. The secondary derivatives of C. glabrata yielded four distinct genotypes
      with varying chromosomal profiles. Proteomic analysis performed by tandem mass
      spectrometry for two of the mutants, CG(L2) and CG(S3), demonstrated a total of
      25 differentially regulated proteins of which 13 were upregulated and 12 were
      downregulated or were similar compared with the parental isolate. The mRNA
      transcript levels of significantly (P<0.001) upregulated genes were determined by
      quantitative RT-PCR analysis, and their physiological relevance in terms of
      phenotypic expression of virulence attributes was verified by conventional
      laboratory methodologies. The data showed that the FL resistance (MIC >256 ug ml(
      1)) of CG(S3) was associated with significantly upregulated (P<0.001) mRNA
      transcript levels of several genes - ERG11, CDR1, CDR2, MFS, MTI, TPR, VPS and
      EFT2 - in addition to a number of other potentially virulent genes expressed
      differentially at a lower level. The results demonstrated accentuated phenotypic
      expression of bud formation of yeast and metallothionein production associated
      with FL resistance in C. glabrata, which may help the fungus to colonize the
      host.

PMID- 23002066
TI  - Haemolytic uraemic syndrome in India due to Shiga toxigenic Escherichia coli.
AB  - The emergence of Shiga toxigenic Escherichia coli (STEC) as a causative agent of
      diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome (HUS) in humans
      is a significant public health concern worldwide. Here we describe a case of HUS
      following dysentery due to STEC. Though STEC is not a major cause of diarrhoea in
      India, we recommend that STEC should be looked for in all cases of bloody
      diarrhoea. To our knowledge, this is the first case of HUS caused by STEC in
      India.

PMID- 23002067
TI  - Molecular typing and resistance mechanisms of imipenem-non-susceptible Klebsiella
      pneumoniae in Taiwan: results from the Taiwan surveillance of antibiotic
      resistance (TSAR) study, 2002-2009.
AB  - We investigated the molecular mechanisms and clonality of imipenem-non
      susceptible Klebsiella pneumoniae isolates collected during a Taiwan national
      surveillance programme, between 2002 and 2009. Genes for carbapenemases, plasmid
      borne ampC-type genes and extended-spectrum beta-lactamase (ESBL) genes were
      analysed by PCR. The major porin channels OmpK35 and OmpK36 were studied by SDS
      PAGE. Molecular typing was performed with pulsed-field gel electrophoresis (PFGE)
      and multi-locus sequence typing (MLST). Our study revealed that all 29 of the
      isolates tested were ESBL producers. Of the K. pneumoniae isolates collected in
      Taiwan from 2002 to 2009, most (84.6 %, 11/13) imipenem-resistant (MIC >2 mg l(
      1)) isolates carried the bla(IMP-8) gene. Isolates with an imipenem MIC of 2 mg
      l(-1) produced ESBLs with or without DHA-1 in combination with OmpK35/36 loss.
      PFGE analysis revealed that six small clusters of isolates were clonally related.
      The MLST grouping results were in concordance with the PFGE results. The
      predominant sequence types (ST) were ST11, ST48 and ST101. Two novel STs, ST1033
      and ST1034, were found. The dominant clone in Taiwan, ST11, has been reported
      worldwide to be associated with various resistance mechanisms.

PMID- 23002068
TI  - Regression models for censored serological data.
AB  - The impact was assessed of censored serological measurements on regression
      equations fitted to data from panels of sera tested by different laboratories,
      for the purpose of standardizing serosurvey results to common units. Several
      methods that adjust for censoring were compared, such as deletion, simple
      substitution, multiple imputation and censored regression. Simulations were
      generated from different scenarios for varying proportions of data censored. The
      scenarios were based on serological panel comparisons tested by different
      national laboratories and assays as part of the European Sero-Epidemiology
      Network 2 project. The results showed that the simple substitution and deletion
      methods worked reasonably well for low proportions of data censored (<20 %).
      However, in general, the censored regression method gave estimates closer to the
      truth than the other methods examined under different scenarios, such as types of
      equations used and violation of regression assumptions. Interval-censored
      regression produced the least biased estimates for assay data resulting from
      dilution series. Censored regression produced the least biased estimates in
      comparison with the other methods examined. Moreover, the results suggest using
      interval-censored regression methods for assay data resulting from dilution
      series.

PMID- 23002069
TI  - Non-rheumatic streptococcal myocarditis - warm hands, warm heart.
AB  - Acute myopericarditis in the developed world is ascribed predominantly to viral
      infections. Enteroviruses and adenoviruses are commonly implicated but are not
      routinely tested for, as the condition is self-limiting and has a good prognosis.
      However, we recently encountered two cases of acute myopericarditis associated
      with concomitant Streptococcus pyogenes [group A Streptococcus (GAS)]
      pharyngotonsillitis. A microbiological aetiology was pursued because of the
      severity of the upper respiratory tract infection and associated systemic illness
      rather than to explain the myopericarditis per se. We report these two cases and
      review the literature of this potentially under-recognized condition. In the
      absence of features of rheumatic fever, we hypothesize a toxin-mediated process
      as opposed to an immune-mediated one. We suggest that perhaps all patients with
      myopericarditis be assessed for GAS pharyngitis.

PMID- 23002070
TI  - Oral Candida colonization in HIV-positive women: associated factors and changes
      following antiretroviral therapy.
AB  - There is a paucity of information about the factors associated with oral
      colonization with Candida species and the changes associated with antiretroviral
      (ARV) therapy. This study investigated the role of ARV therapy and other factors
      in a study population. Relevant clinical and laboratory information was obtained
      and oral rinse specimens were tested for yeast identification. The findings were
      compared with previous data from the same clinic before ARV therapy was
      available. Of 197 patients, 117 (59.4 %) were colonized. Candida albicans was the
      dominant species (71 %) and Candida dubliniensis was the most frequent non
      albicans Candida. The colonized group had a higher rate of concurrent
      tuberculosis (TB) infection (77.4 % compared with 56 % in the non-colonized
      patients, P = 0.03) and a lower median CD4(+) count (346.5 cells mm(-3)) compared
      with the non-colonized group (418 cells mm(-3)). Participants not on ARV therapy
      and those having oral prosthesis were all colonized (P = 0.003 and P = 0.022,
      respectively). The oral Candida count was negatively correlated with the CD4(+)
      count in participants on ARV therapy (P = 0.006). Associated factors using
      logistic regression were dental caries (odds ratio = 1.30; 95 % confidence
      interval = 1.07-1.60] and diabetes mellitus (odds ratio = 5.52; 95 % confidence
      interval = 1.68-18.12). The colonization rate was higher (81.3 %) as well as the
      yeast count before ARV therapy was available, while the prevalence of C.
      dubliniensis was found to have increased from 6.3 to 11 %. Dental caries,
      diabetes mellitus, oral prostheses and TB infection were associated with oral
      colonization. The colonization rate, variety and yeast counts declined with ARV
      therapy.

PMID- 23002071
TI  - Maternal oral origin of Fusobacterium nucleatum in adverse pregnancy outcomes as
      determined using the 16S-23S rRNA gene intergenic transcribed spacer region.
AB  - Fusobacterium nucleatum, a common Gram-negative anaerobe prevalent in the oral
      cavity, possesses the ability to colonize the amniotic cavity and the fetus.
      However, F. nucleatum may also be part of the vaginal microbiota from where it
      could reach the amniotic tissues. Due to the heterogeneity of F. nucleatum,
      consisting of five subspecies, analysis at the subspecies/strain level is
      desirable to determine its precise origin. The aims of this study were: (i) to
      evaluate the use of the 16S-23S rRNA gene intergenic transcribed spacer (ITS)
      region as a tool to differentiate subspecies of F. nucleatum, and (ii) to design
      a simplified technique based on the ITS to determine the origin of F. nucleatum
      strains associated with adverse pregnancy outcomes. Amplified fragments of the
      16S-23S rRNA gene ITS region corresponding to the five subspecies of F. nucleatum
      were subjected to cloning and sequencing to characterize the different ribosomal
      operons of the subspecies. Distinctive length and sequence patterns with
      potential to be used for identification of the subspecies/strain were identified.
      These were used to evaluate the origin of F. nucleatum identified in neonatal
      gastric aspirates (swallowed amniotic fluid) by sequence comparisons with the
      respective oral and vaginal maternal samples. A simplified technique using a
      strain-specific primer in a more sensitive nested PCR was subsequently developed
      to analyse ten paired neonatal-maternal samples. Analysing the variable fragment
      of the ITS region allowed the identification of F. nucleatum subsp. polymorphum
      from an oral origin as potentially being involved in neonatal infections. Using a
      strain-specific primer, the F. nucleatum subsp. polymorphum strain was detected
      in both neonatal gastric aspirates and maternal oral samples in cases of preterm
      birth from mothers presenting with localized periodontal pockets. Interestingly,
      the same strain was not present in the vaginal sample of any case investigated.
      The 16S-23S rRNA gene ITS can be a useful tool to determine the origin of F.
      nucleatum. The results of this study strongly indicate that F. nucleatum subsp.
      polymorphum of oral origin could be involved with pregnancy complications.

PMID- 23002072
TI  - Harnessing the genome: development of a hierarchical typing scheme for meticillin
      resistant Staphylococcus aureus.
AB  - A major barrier to using genome sequencing in medical microbiology is the ability
      to interpret the data. New schemes that provide information about the importance
      of sequence variation in both clinical and public health settings are required.
      Meticillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial
      pathogen that is being observed with increasing frequency in community settings.
      Better tools are needed to improve our understanding of its transmissibility and
      micro-epidemiology in order to develop effective interventions. Using DNA
      microarray technology we identified a set of 20 binary targets whose presence or
      absence could be determined by PCR, producing a PCR binary typing scheme (PCR
      BT). This was combined with multi-locus sequence type-based, sequence nucleotide
      polymorphism typing to form a hierarchical typing scheme. When applied to a set
      of epidemiologically unrelated isolates, a high degree of concordance was
      observed with PFGE (98.8 %). The scheme was able to detect the presence or
      absence of an outbreak strain in eight out of nine outbreak investigations,
      demonstrating epidemiological concordance. PCR-BT was better than PFGE at
      distinguishing between outbreak strains, particularly where epidemic MRSA-15 was
      involved. The method developed here is a rapid, digital typing scheme for S.
      aureus for use in both micro- and macro-epidemiological investigations that has
      the advantage of being suitable for use in routine diagnostic laboratories. The
      targets are defined and therefore the types can be defined by any platform
      capable of detecting the sequences used, including whole genome sequencing.

PMID- 23002073
TI  - Street conflict mediation to prevent youth violence: conflict characteristics and
      outcomes.
AB  - BACKGROUND: Mediation of potentially violent conflicts is a key component of
      CeaseFire, an effective gun violence-prevention programme. OBJECTIVE: To describe
      conflicts mediated by outreach workers (OW) in Baltimore's CeaseFire replication,
      examine neighbourhood variation, and measure associations between conflict risk
      factors and successful nonviolent resolution. METHODS: A cross-sectional study
      was conducted using records for 158 conflicts mediated between 2007 and 2009.
      Involvement of youth, gangs, retaliation, weapons and other risk factors were
      described. Principal component analysis (PCA) was used for data-reduction
      purposes before the relationship between conflict risk components and mediation
      success was assessed with multivariate logistic regression. RESULTS: Most
      conflicts involved 2-3 individuals. Youth, persons with a history of violence,
      gang members and weapons were commonly present. OWs reported immediate,
      nonviolent resolution for 65% of mediated conflicts; an additional 23% were at
      least temporarily resolved without violence. PCA identified four dimensions of
      conflict risk: the risk-level of individuals involved; whether the incident was
      related to retaliation; the number of people involved; and shooting likelihood.
      However, these factors were not related to the OW's ability to resolve the
      conflict. Neighbourhoods with programme-associated reductions in homicides
      mediated more gang-related conflicts; neighbourhoods without programme-related
      homicide reductions encountered more retaliatory conflicts and more weapons.

PMID- 23002074
TI  - Use of patient reported outcome questionnaires in the urogynecologic literature.
AB  - AIMS: We aimed to describe the current use of patient reported outcome
      questionnaires (PROQ) in the urogynecologic literature. METHODS: All articles
      from 2009 in 11 journals were reviewed and included if PROQ were used. PROQ were
      assigned the grades of recommendation used by the International Consultation on
      Incontinence (ICI). Data were collected by two independent reviewers (differences
      resolved by consensus). Fisher and chi(2) tests were used for statistics.
      RESULTS: Of the 212 articles included, 126 used multiple PROQ. Seventy-two
      percent used at least one grade A PROQ and 42% exclusively used grade A PROQ.
      Articles about urinary incontinence (UI) were more likely to use grade A PROQ
      than those pertaining to interstitial cystitis or anal incontinence. Eighty-three
      articles used PROQ in non-English languages. These articles were as likely to use
      ICI grade A PROQ as those using English PROQ. When translated questionnaires are
      used, 41.5% of articles did not provide references for a validation of the
      translated version. Eighty-seven different PROQ were identified and used 422
      times. Of those, 75 were developed in English. Short versions were used more
      frequently. PROQ available online were used 9.4 times more frequently than those
      requiring payment. The more utilized PROQ were more often grade A than those
      rarely used (P < 0.001). CONCLUSIONS: Using multiple PROQ is common in the
      literature reviewed. 72.2% of articles used at least one PROQ with the highest
      ICI recommendation but only 42% used exclusively those. Short and easily
      available PROQ were used more often. Most PROQ are developed in English.

PMID- 23002075
TI  - Hypoxia-induced endothelial CX3CL1 triggers lung smooth muscle cell phenotypic
      switching and proliferative expansion.
AB  - Distal arterioles with limited smooth muscles help maintain the high blood flow
      and low pressure in the lung circulation. Chronic hypoxia induces lung distal
      vessel muscularization. However, the molecular events that trigger alveolar
      hypoxia-induced peripheral endothelium modulation of vessel wall smooth muscle
      cell (SMC) proliferation and filling of nonmuscular areas are unclear. Here, we
      investigated the role of CX3CL1/CX3CR1 system in endothelial-SMC cross talk in
      response to hypoxia. Human lung microvascular endothelial cells responded to
      alveolar oxygen deficiency by overproduction of the chemokine CX3CL1. The CX3CL1
      receptor CX3CR1 is expressed by SMCs that are adjacent to the distal endothelium.
      Hypoxic release of endothelial CX3CL1 induced SMC phenotypic switching from the
      contractile to the proliferative state. Inhibition of CX3CR1 prevented CX3CL1
      stimulation of SMC proliferation and monolayer expansion. Furthermore, CX3CR1
      deficiency attenuated spiral muscle expansion, distal vessel muscularization, and
      pressure elevation in response to hypoxia. Our findings indicate that the
      capillary endothelium relies on the CX3CL1-CX3CR1 axis to sense alveolar hypoxia
      and promote peripheral vessel muscularization. These results have clinical
      significance in the development of novel therapeutics that target mechanisms of
      distal arterial remodeling associated with pulmonary hypertension induced by
      oxygen deficiency that is present in people living at high altitudes and patients
      with obstructive lung diseases.

PMID- 23002076
TI  - Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix
      remodeling, and oxidative stress activation induced by chronic inflammation.
AB  - Several studies have demonstrated the importance of Rho-kinase in the modulation
      of smooth muscle contraction, airway hyperresponsiveness, and inflammation.
      However, the effects of repeated treatment with a specific inhibitor of this
      pathway have not been previously investigated. We evaluated the effects of
      repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on
      airway hyperresponsiveness, oxidative stress activation, extracellular matrix
      remodeling, eosinophilic inflammation, and cytokine expression in an animal model
      of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or
      saline exposures. The treatment with Y-27632 (1 mM) started at the fifth
      inhalation. Seventy-two hours after the seventh inhalation, the animals'
      pulmonary mechanics were evaluated, and exhaled nitric oxide (E(NO)) was
      collected. The lungs were removed, and histological analysis was performed using
      morphometry. Treatment with Y-27632 in sensitized animals reduced E(NO)
      concentrations, maximal responses of resistance, elastance of the respiratory
      system, eosinophil counts, collagen and elastic fiber contents, the numbers of
      cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase,
      matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming
      growth factor-beta, NF-kappaB, IFN-gamma, and 8-iso-prostaglandin F2alpha
      contents compared with the untreated group (P < 0.05). We observed positive
      correlations among the functional responses and inflammation, remodeling, and
      oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase
      pathway activation contributes to the potentiation of the hyperresponsiveness,
      inflammation, the extracellular matrix remodeling process, and oxidative stress
      activation. These results suggest that Rho-kinase inhibitors represent potential
      pharmacological tools for the control of asthma.

PMID- 23002077
TI  - Estrogen effects on human airway smooth muscle involve cAMP and protein kinase A.
AB  - Clinically observed differences in airway reactivity and asthma exacerbations in
      women at different life stages suggest a role for sex steroids in modulating
      airway function although their targets and mechanisms of action are still being
      explored. We have previously shown that clinically relevant concentrations of
      exogenous estrogen acutely decrease intracellular calcium ([Ca(2+)](i)) in human
      airway smooth muscle (ASM), thereby facilitating bronchodilation. In this study,
      we hypothesized that estrogens modulate cyclic nucleotide regulation, resulting
      in decreased [Ca(2+)](i) in human ASM. In Fura-2-loaded human ASM cells, 1 nM
      17beta-estradiol (E(2)) potentiated the inhibitory effect of the beta
      adrenoceptor (beta-AR) agonist isoproterenol (ISO; 100 nM) on histamine-mediated
      Ca(2+) entry. Inhibition of protein kinase A (PKA) activity (KT5720; 100 nM)
      attenuated E(2) effects on [Ca(2+)](i). Acute treatment with E(2) increased cAMP
      levels in ASM cells comparable to that of ISO (100 pM). In acetylcholine
      contracted airways from female guinea pigs or female humans, E(2) potentiated ISO
      induced relaxation. These novel data suggest that, in human ASM, physiologically
      relevant concentrations of estrogens act via estrogen receptors (ERs) and the
      cAMP pathway to nongenomically reduce [Ca(2+)](i), thus promoting
      bronchodilation. Activation of ERs may be a novel adjunct therapeutic avenue in
      reactive airway diseases in combination with established cAMP-activating
      therapies such as beta(2)-agonists.

PMID- 23002078
TI  - New methods for monitoring dynamic airway tissue oxygenation and perfusion in
      experimental and clinical transplantation.
AB  - A dual circulation, supplied by bronchial and pulmonary artery-derived vessels,
      normally perfuses the airways from the trachea to the terminal bronchioles. This
      vascular system has been highly conserved through mammalian evolution and is
      disrupted at the time of lung transplantation. In most transplant centers, this
      circulation is not restored. The Papworth Hospital Autopsy study has revealed
      that an additional attrition of periairway vessels is associated with the
      development of chronic rejection, otherwise known as the bronchiolitis obliterans
      syndrome (BOS). Experimental studies subsequently demonstrated that airway
      vessels are subject to alloimmune injury and that the loss of a functional
      microvascular system identifies allografts that cannot be rescued with
      immunosuppressive therapy. Therefore, surgical and medical strategies, which
      preserve the functionality of the existent vasculature in lung transplant
      patients, may conceivably limit the incidence of BOS. Given these unique anatomic
      and physiological considerations, there is an emerging rationale to better
      understand the perfusion and oxygenation status of airways in transplanted lungs.
      This article describes novel methodologies, some newly developed by our group,
      for assessing airway tissue oxygenation and perfusion in experimental and
      clinical transplantation.

PMID- 23002079
TI  - Limb abnormalities on trisomy 18: evidence for early diagnosis.
AB  - OBJECTIVE: To assess the frequency and types of limb abnormalities observed among
      patients with trisomy 18, or Edwards syndrome (ES). METHOD: The sample consisted
      of consecutive patients evaluated by a clinical genetics service in the period
      from 1975 to 2008. The results of the cytogenetic analysis, as well as the
      clinical data were retrieved from the medical records, with special attention to
      limb abnormalities findings. All the karyotype analysis was performed at the same
      laboratory. RESULTS: During the study period, 50 patients were identified, 33
      (66%) of them females, with ages at the first evaluation ranging from 1 day to 16
      years (median 14 days). The single lineage with free trisomy 18 was the most
      frequent chromosomal disorder (90%). Mosaicism was observed in 10% of the cases.
      Clenched fist with overlapping fingers was the predominant anomaly of the upper
      limbs (70%). Other common disorders included the single palmar crease (42%) and
      hypoplastic nails (36%). Radial abnormalities were found in 11 patients (22%). As
      for the lower limbs, hypoplastic nails were the most common abnormality (58%),
      followed by the rocker bottom foot with prominent calcaneus (50%). One patient
      had unilateral ectrodactyly as well. CONCLUSIONS: Despite the classical
      description, limb anomalies can be much variable in ES. Some patients may show
      unusual abnormalities, such as radial defects and ectrodactyly. These findings
      are extremely important for the clinical suspicion and early identification of
      patients with ES.

PMID- 23002081
TI  - Factors mediating the relationship between intimate partner violence and chronic
      pain in Chinese women.
AB  - There is increasing recognition that chronic pain is a problem affecting women
      survivors of intimate partner violence (IPV), and in Western literature evidence
      is emerging about significant factors mediating the relationship between IPV and
      chronic pain. However, little is known about the factors mediating IPV and
      chronic pain in Chinese women for whom prior research has shown that Chinese
      culture may influence their response to IPV. This study was conducted to assess
      the roles of posttraumatic stress disorder (PTSD) symptoms, depressive symptoms,
      and IPV-related injury on the relationship between IPV and chronic pain in
      Chinese women, using structural equation modelling (SEM). Data were collected
      from 308 Chinese women survivors of IPV recruited at community setting (n = 228)
      and at domestic violence shelters (n = 82). Results showed that only the
      relationship between psychological abuse severity and chronic pain severity was
      mediated by PTSD symptom severity (beta = .30, 95% CI = 0.14-0.45, p < .001).
      Furthermore, although depressive symptom severity was strongly correlated with
      PTSD symptom severity (beta = .69, 95% CI = 0.61-0.76, p < .001), it was not
      found to be mediating the relationship between any types of IPV and chronic pain.
      Similarly, IPV-related injury severity was not shown to have a significant
      mediating effect on the relationship between IPV and chronic pain. The findings
      affirm the importance of recognizing the complex interrelationships among IPV,
      mental health symptoms, and physical health problems as well as the need for
      considering PTSD symptoms when designing interventions for abused Chinese women
      with complaints of chronic pain.

PMID- 23002080
TI  - Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells
      via melatonin-regulation of GSK3beta.
AB  - Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer,
      but the underlying mechanisms are unknown. Employing a tissue-isolated human
      breast xenograft tumor nude rat model, we observed that glycogen synthase kinase
      3beta (GSK3beta), an enzyme critical in metabolism and cell
      proliferation/survival, exhibits a circadian rhythm of phosphorylation in human
      breast tumors. Exposure to light-at-night suppresses the nocturnal pineal
      melatonin synthesis, disrupting the circadian rhythm of GSK3beta phosphorylation.
      Melatonin activates GSK3beta by inhibiting the serine-threonine kinase Akt
      phosphorylation, inducing beta-catenin degradation and inhibiting epithelial-to
      mesenchymal transition, a fundamental process underlying cancer metastasis. Thus,
      chronic circadian disruption by light-at-night via occupational exposure or age
      related sleep disturbances may contribute to cancer incidence and the metastatic
      spread of breast cancer by inhibiting GSK3beta activity and driving epithelial-to
      mesenchymal transition in breast cancer patients.

PMID- 23002082
TI  - Adjuvant use of intravenous immunoglobulin in the treatment of neonatal sepsis: a
      systematic review with a meta-analysis.
AB  - OBJECTIVE: To evaluate whether intravenous immunoglobulin reduces mortality and
      length of hospital stay in the treatment of neonatal sepsis. SOURCES: The MEDLINE
      database was searched. The keywords were combined using the following search
      strategy: [(sepsis OR shock, septic OR infection) AND immunoglobulins,
      intravenous] AND infant, newborn. Only randomized clinical trials (RCTs) showing
      good methodological quality and assessing the effect of adjuvant intravenous
      immunoglobulin in the treatment of neonatal sepsis were selected for inclusion
      and data analysis. SUMMARY OF THE FINDINGS: Seven RCTs were selected. All of them
      evaluated the mortality rate, including 3,756 patients. The global effect of this
      outcome showed no statistically significant difference between the groups. Only
      five studies evaluated the mean length of hospital stay, including 3,672
      patients. Although there is a statistically significant reduction of 1.24 days in
      the length of hospital stay with the use of intravenous immunoglobulin, such
      difference is clinically irrelevant and its high cost does not warrant its
      routine use in medical practice. The data reported in the present review
      contradict the review by Ohlsson et al., which was updated in 2010 and showed
      significant benefit with the use of intravenous immunoglobulin on both outcomes.
      CONCLUSIONS: We concluded that the use of adjuvant intravenous immunoglobulin
      shows no benefit regarding mortality, whereas the reduction in the length of
      hospital stay is irrelevant.

PMID- 23002083
TI  - Impaired fasting glucose and risk of cardiovascular disease in Korean men and
      women: the Korean Heart Study.
AB  - OBJECTIVE: The relationship between impaired fasting glucose (IFG) and risk of
      cardiovascular disease (CVD) or ischemic heart disease (IHD) varies widely
      according to sex and ethnicity. We evaluated the relationship between IFG and CVD
      or IHD among Korean men and women. RESEARCH DESIGN AND METHODS: A total of
      408,022 individuals who underwent voluntary private health examinations in 17
      centers in South Korea were followed for 10 years. Data regarding CVD or IHD
      events were obtained from the Korean National Health Insurance database. IFG was
      categorized as grade 1 (fasting glucose 100-109 mg/dL) or grade 2 (110-125
      mg/dL). RESULTS: Incidence rates of CVD (per 100,000 person-years) were 2,203 for
      diabetes. Age-adjusted hazard ratios (HRs) for CVD were 1.17 (95% CI 1.13-1.20)
      for grade 1 IFG, 1.30 (1.24-1.35) for grade 2 IFG, and 1.81 (1.75-1.86) for
      diabetes. The increased risk for women was similar to that of men. Age-adjusted
      HRs for IHD and ischemic stroke were also significantly increased for men and
      women with IFG and diabetes. After multivariate adjustment of conventional risk
      factors (hypertension, dyslipidemia, smoking, obesity, and family history of
      CVD), the overall risk of CVD was greatly attenuated in all categories. However,
      the HRs for IHD and ischemic stroke remained significantly increased in men for
      grade 2 IFG but not in women. CONCLUSIONS: In Korea, grade 2 IFG is associated
      with increased risk of IHD and ischemic stroke, independent of other conventional
      risk factors, in men but not in women.

PMID- 23002084
TI  - Diabetes is an independent predictor for severe osteoarthritis: results from a
      longitudinal cohort study.
AB  - OBJECTIVE: To evaluate if type 2 diabetes is an independent risk predictor for
      severe osteoarthritis (OA). RESEARCH DESIGN AND METHODS: Population-based cohort
      study with an age- and sex-stratified random sample of 927 men and women aged 40
      80 years and followed over 20 years (1990-2010). RESULTS: Rates of arthroplasty
      (95% CI) were 17.7 (9.4-30.2) per 1,000 person-years in patients with type 2
      diabetes and 5.3 (4.1-6.6) per 1,000 person-years in those without (P < 0.001).
      Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard
      ratios (95% CI), 3.8 (2.1-6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1
      3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA.
      The probability of arthroplasty increased with disease duration of type 2
      diabetes and applied to men and women, as well as subgroups according to age and
      BMI. Our findings were corroborated in cross-sectional evaluation by more severe
      clinical symptoms of OA and structural joint changes in subjects with type 2
      diabetes compared with those without type 2 diabetes. CONCLUSIONS: Type 2
      diabetes predicts the development of severe OA independent of age and BMI. Our
      findings strengthen the concept of a strong metabolic component in the
      pathogenesis of OA.

PMID- 23002085
TI  - Depression as a predictor of weight regain among successful weight losers in the
      diabetes prevention program.
AB  - OBJECTIVE: To determine whether depression symptoms or antidepressant medication
      use predicts weight regain in overweight individuals with impaired glucose
      tolerance (IGT) who are successful with initial weight loss. RESEARCH DESIGN AND
      METHODS: A total of 1,442 participants who successfully lost at least 3% of their
      baseline body weight after 12 months of participation in the randomized
      controlled Diabetes Prevention Program (DPP) continued in their assigned
      treatment group (metformin, intensive lifestyle, or placebo) and were followed
      into the Diabetes Prevention Program Outcome Study (DPPOS). Weight regain was
      defined as a return to baseline DPP body weight. Participant weight and
      antidepressant medication use were assessed every 6 months. Depression symptoms
      (Beck Depression Inventory [BDI] score >=11) were assessed every 12 months.
      RESULTS: Only 2.7% of the overall cohort had moderate to severe depression
      symptoms at baseline; most of the participants with BDI score >=11 had only mild
      symptoms during the period of observation. In unadjusted analyses, both
      depression symptoms (hazard ratio 1.31 [95% CI 1.03-1.67], P = 0.03) and
      antidepressant medication use at either the previous visit (1.72 [1.37-2.15], P <
      0.0001) or cumulatively as percent of visits (1.005 [1.002-1.008], P = 0.0003)
      were predictors of subsequent weight regain. After adjustment for multiple
      covariates, antidepressant use remained a significant predictor of weight regain
      (P < 0.0001 for the previous study visit; P = 0.0005 for the cumulative measure),
      while depression symptoms did not. CONCLUSIONS: In individuals with IGT who do
      not have severe depression and who initially lose weight, antidepressant use may
      increase the risk of weight regain.

PMID- 23002086
TI  - The effects of free-living interval-walking training on glycemic control, body
      composition, and physical fitness in type 2 diabetic patients: a randomized,
      controlled trial.
AB  - OBJECTIVE: To evaluate the feasibility of free-living walking training in type 2
      diabetic patients and to investigate the effects of interval-walking training
      versus continuous-walking training upon physical fitness, body composition, and
      glycemic control. RESEARCH DESIGN AND METHODS: Subjects with type 2 diabetes were
      randomized to a control (n = 8), continuous-walking (n = 12), or interval-walking
      group (n = 12). Training groups were prescribed five sessions per week (60
      min/session) and were controlled with an accelerometer and a heart-rate monitor.
      Continuous walkers performed all training at moderate intensity, whereas interval
      walkers alternated 3-min repetitions at low and high intensity. Before and after
      the 4-month intervention, the following variables were measured: VO(2)max, body
      composition, and glycemic control (fasting glucose, HbA(1c), oral glucose
      tolerance test, and continuous glucose monitoring [CGM]). RESULTS: Training
      adherence was high (89 +/- 4%), and training energy expenditure and mean
      intensity were comparable. VO(2)max increased 16.1 +/- 3.7% in the interval
      walking group (P < 0.05), whereas no changes were observed in the continuous
      walking or control group. Body mass and adiposity (fat mass and visceral fat)
      decreased in the interval-walking group only (P < 0.05). Glycemic control
      (elevated mean CGM glucose levels and increased fasting insulin) worsened in the
      control group (P < 0.05), whereas mean (P = 0.05) and maximum (P < 0.05) CGM
      glucose levels decreased in the interval-walking group. The continuous walkers
      showed no changes in glycemic control. CONCLUSIONS: Free-living walking training
      is feasible in type 2 diabetic patients. Continuous walking offsets the
      deterioration in glycemia seen in the control group, and interval walking is
      superior to energy expenditure-matched continuous walking for improving physical
      fitness, body composition, and glycemic control.

PMID- 23002087
TI  - Arterial stiffness is inversely related to plasma adiponectin levels in young
      normotensive patients with type 1 diabetes.
AB  - OBJECTIVE This study investigated the association between arterial stiffness and
      plasma adiponectin in patients with type 1 diabetes.  RESEARCH DESIGN AND METHODS
      Participants were normotensive patients with type 1 diabetes who were up to age
      40 years. Subjects on statins with macrovascular disease or overt nephropathy
      were excluded. Large artery stiffness was assessed by measurement of carotid
      femoral pulse wave velocity (PWV), whereas plasma adiponectin was measured by
      radioimmunoassay.  RESULTS Data from 80 patients (age 27.1 +/- 6.1 years, BMI
      24.2 +/- 3.1 kg/m(2), HbA(1c) 7.5 +/- 1.6%, 39 men, adiponectin 13.9 +/- 6.7
      MUg/mL, and PWV 5.6 +/- 0.9 m/s) were analyzed. Log adiponectin inversely
      correlated with age-adjusted PWV (r = -0.291, P = 0.009) and waist circumference
      (r = -0.427, P < 0.001). In a fully adjusted model, age, expiration/inspiration
      index, and log adiponectin were independently associated with PWV, explaining
      39.6% of its variance.  CONCLUSIONS Arterial stiffness is inversely related to
      adiponectin concentration in young patients with type 1 diabetes without major
      complications.

PMID- 23002088
TI  - A single-nucleotide polymorphism rs4639966 in 11q23.3 is associated with clinical
      features of systemic lupus erythematosus in the Chinese population.
AB  - In our previous genome-wide association study (GWAS), we identified an
      association signal of the single-nucleotide polymorphism (SNP) rs4639966 (p =
      1.25 * 10(-16), odds ratio [OR] = 1.29) within 11q23.3. The aim of this study was
      to investigate its relationship with disease subphenotypes, including renal
      nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar
      rash, discoid rash, immunological disorder, oral ulcer, hematological disorder,
      neurological disorder, serositis, arthritis and vasculitis. In this study, we
      used 4199 cases and 8255 controls from our previous GWAS to explore the
      association between 11q23.3 with subphenotypes of systemic lupus erythematosus
      (SLE). Data were analyzed with PLINK 1.07 software. Significant associations were
      found for the SNP rs4639966 of 11q23.3 with SLE of age at diagnosis <20 years (OR
      = 1.18, p = 0.0049), malar rash (OR = 1.13, p = 0.01) and vasculitis (OR = 1.17,
      p = 0.02). The study suggested that 11q23.3 might not only play important roles
      in the development of SLE, but also contribute to the complex phenotypes of SLE.

PMID- 23002089
TI  - When did decapods invade hydrothermal vents? Clues from the Western Pacific and
      Indian Oceans.
AB  - Hydrothermal vents are typically located in midocean ridges and back-arc basins
      and are usually generated by the movement of tectonic plates. Life thrives in
      these environments despite the extreme conditions. In addition to
      chemoautotrophic bacteria, decapod crustaceans are dominant in many of the
      hydrothermal vents discovered to date. Contrary to the hypothesis that these
      species are remnants of relic fauna, increasing evidence supports the notion that
      hydrothermal vent decapods have diversified in more recent times with previous
      research attributing the origin of alvinocarid shrimps to the Miocene. This study
      investigated seven representative decapod species from four hydrothermal vents
      throughout the Western Pacific and Indian Oceans. A partitioned mix-model
      phylogenomic analysis of mitochondrial DNA produced a consistent phylogenetic
      topology of these vent-endemic species. Additionally, molecular dating analysis
      calibrated using multiple fossils suggested that both bythograeid crabs and
      alvinocarid shrimps originated in the late Mesozoic and early Cenozoic. Although
      of limited sampling, our estimates support the extinction/repopulation
      hypothesis, which postulates recent diversification times for most hydrothermal
      vent species due to their mass extinction by global deep-water anoxic/dysoxic
      events during the Late Cretaceous and Early Tertiary. The continental-derived
      property of the West Pacific province is compatible with the possibility that
      vent decapods diversified from ancestors from shallow-water regions such as cold
      seeps. Our results move us a step closer toward understanding the evolutionary
      origin of hydrothermal vent species and their distribution in the Western Pacific
      Indian Ocean Region.

PMID- 23002090
TI  - Improving phylogenetic inference with a semiempirical amino acid substitution
      model.
AB  - Amino acid substitution matrices describe the rates by which amino acids are
      replaced during evolution. In contrast to nucleotide or codon models, amino acid
      substitution matrices are in general parameterless and empirically estimated,
      probably because there is no obvious parametrization for amino acid
      substitutions. Principal component analysis has previously been used to improve
      codon substitution models by empirically finding the most relevant parameters.
      Here, we apply the same method to amino acid substitution matrices, leading to a
      semiempirical substitution model that can adjust the transition rates to the
      protein sequences under investigation. Our new model almost invariably achieves
      the best likelihood values in large-scale comparisons with established amino acid
      substitution models (JTT, WAG, and LG). In particular for longer alignments,
      these likelihood gains are considerably larger than what could be expected from
      simply having more parameters. The application of our model differs from that of
      mixture models (such as UL2 or UL3), as we optimize one rate matrix per
      alignment, whereas mixture models apply the variation per alignments site. This
      makes our model computationally more efficient, while the performance is
      comparable to that of UL3. Applied to the phylogenetic problem of the origin of
      placental mammals, our new model and the UL3 mixed model are the only ones of the
      tested models that cluster Afrotheria and Xenarthra into a clade called
      Atlantogenata, which would be in correspondence with recent findings using more
      sophisticated phylogenetic methods.

PMID- 23002091
TI  - Anti-IL-20 monoclonal antibody alleviates inflammation in oral cancer and
      suppresses tumor growth.
AB  - Interleukin-20 (IL-20) is a proinflammatory cytokine involved in rheumatoid
      arthritis, atherosclerosis, and osteoporosis. However, little is known about the
      role of IL-20 in oral cancer. We explored the function of IL-20 in the tumor
      progression of oral cancer. IL-20 expression levels in tumorous and nontumorous
      oral tissue specimens from 40 patients with four different stages oral cancer
      were analyzed with immunohistochemistry (IHC) staining and quantitative real-time
      PCR (qRT-PCR). Expression of IL-20 and its receptor subunits was higher in
      clinical oral tumor tissue than in nontumorous oral tissue. The role of IL-20 was
      examined in two oral cancer cell lines (OC-3 and OEC-M1). In vitro, IL-20
      promoted TNF-alpha, IL-1beta, MCP-1, CCR4, and CXCR4 and increased proliferation,
      migration, reactive oxygen species (ROS) production, and colony formation of oral
      cancer cells via activated STAT3 and AKT/JNK/ERK signals. To evaluate the
      therapeutic potential of anti-IL-20 monoclonal antibody 7E for treating oral
      cancer, an ex vivo tumor growth model was used. In vivo, 7E reduced tumor growth
      and inflammation in oral cancer cells. In conclusion, IL-20 promoted oral tumor
      growth, migration, and tumor-associated inflammation. Therefore, IL-20 may be a
      novel target for treating oral cancer, and anti-IL-20 monoclonal antibody 7E may
      be a feasible therapeutic.

PMID- 23002092
TI  - Exclusive bottle feeding of either formula or breast milk is associated with
      greater infant weight gain than exclusive breastfeeding, but findings may not
      reflect a causal effect of bottle feeding.

PMID- 23002093
TI  - High-intensity interventions promote smoking cessation among hospitalized
      patients.

PMID- 23002094
TI  - Targeting olfactomedin-like 3 inhibits tumor growth by impairing angiogenesis and
      pericyte coverage.
AB  - Antiangiogenic drugs have been used as anticancer agents to target tumor
      endothelial cells or pericytes. Because of limited efficacy of the current
      monotherapies, there is a strong demand for the dual targeting of endothelial
      cells and pericytes. Here, we identify Olfactomedin-like 3 (Olfml3) as a novel
      proangiogenic cue within the tumor microenvironment. Tumor-derived Olfml3 is
      produced by both tumor endothelial cells and accompanying pericytes and deposited
      in the perivascular compartment. Blockade of Olfml3 by anti-Olfml3 antibodies is
      highly effective in reducing tumor vascularization, pericyte coverage, and tumor
      growth. In vitro, Olfml3 targeting is sufficient to inhibit endothelioma cell
      migration and sprouting. Olfml3 alone or through binding to BMP4 enhances the
      canonical SMAD1/5/8 signaling pathway required for BMP4-induced angiogenesis.
      Therefore, Olfml3 blockade provides a novel strategy to control tumor growth by
      targeting two distinct cell types within the tumor microenvironment using a
      single molecule.

PMID- 23002095
TI  - Drop the language of disorder.

PMID- 23002096
TI  - Catheter-related complications in cancer patients on home parenteral nutrition: a
      prospective study of over 51,000 catheter days.
AB  - BACKGROUND: Although home parenteral nutrition (HPN) is often indicated in cancer
      patients, many physicians are concerned about the risks potentially associated
      with the use of central venous access devices (VADs) in these patients. The aim
      of this prospective study was to investigate the actual incidence of VAD-related
      complications in cancer patients on HPN. METHODS: All adult cancer patient
      candidates for VAD insertion and HPN were enrolled. The incidence of
      complications associated with 4 types of VADs (peripherally inserted central
      catheter [PICC], Hohn catheter, tunneled Groshong catheter, and port) was
      investigated, as well as the most significant risk factors. RESULTS: Two hundred
      eighty-nine VADs in 254 patients were studied, for a total of 51,308 catheter
      days. The incidence of catheter-related bloodstream infections (CRBSIs) was low
      (0.35/1000 catheter-days), particularly for PICCs (0/1000; P < .01 vs Hohn and
      tunneled catheters) and for ports (0.19/1000; P < .01 vs Hohn and P < .05 vs
      tunneled catheters). Mechanical complications were uncommon (0.8/1000), as was
      VAD-related venous thrombosis (0.06/1000). Ultrasound-guided venipuncture was
      associated with a decreased risk of CRBSI (P < .04) and thrombosis (P < .001).
      VAD securement using sutureless devices reduced the risk of CRBSI and dislocation
      (P < .001). Hohn catheters had no advantage over PICCs (higher complication rate
      and shorter dwell time; P < .001). CONCLUSIONS: In cancer patients, HPN can be
      safely carried out with a low incidence of complications. Also, VADs are not
      equal in terms of complication rates, and strict adherence to meticulous
      insertion policies may effectively reduce catheter-related complications.

PMID- 23002097
TI  - Regulatory T cells reduce acute lung injury fibroproliferation by decreasing
      fibrocyte recruitment.
AB  - Acute lung injury (ALI) causes significant morbidity and mortality.
      Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing
      fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are
      important in lung injury resolution. Their role in fibroproliferation is unknown.
      We sought to identify the role of Tregs in ALI fibroproliferation, using a murine
      model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice
      received intratracheal LPS. Fibroproliferation was characterized by histology and
      the measurement of lung collagen. Lung fibrocytes were measured by flow
      cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice
      received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of
      LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)
      CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the
      CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice
      demonstrated significant collagen deposition on Day 3 after LPS. WT mice
      exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent
      fibrosis. This fibrosis was mediated by the sustained epithelial expression of
      CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte
      recruitment. The adoptive transfer of Tregs resolved fibroproliferation by
      decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of
      the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and
      fibroproliferation. These results indicate a central role for Tregs in the
      resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the
      CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation
      may inform the design of new therapeutic tools for patients with ALI.

PMID- 23002098
TI  - Glutathione peroxidase-1 reduces influenza A virus-induced lung inflammation.
AB  - Oxidative stress caused by excessive reactive oxygen species production is
      implicated in influenza A virus-induced lung disease. Glutathione peroxidase
      (GPx)-1 is an antioxidant enzyme that may protect lungs from such damage. The
      objective of this study was to determine if GPx-1 protects the lung against
      influenza A virus-induced lung inflammation in vivo. Male wild-type (WT) or GPx
      1(-/-) mice were inoculated with HKx31 (H3N2, 1 * 10(4) plaque-forming units),
      and bronchoalveolar lavage fluid (BALF)/lung compartments were analyzed on Days 3
      and 7 after infection for inflammatory marker expression, histology, and viral
      titer. WT mice infected with HKx31 had significantly more BALF total cells,
      macrophages, neutrophils, and lymphocytes at Days 3 and 7 compared with naive WT
      animals (n = 5-8; P < 0.05). However, infected GPx-1(-/-) mice had significantly
      more BALF inflammation, which included more total cells, macrophages, and
      neutrophils, compared with WT mice, and this was abolished by treatment with the
      GPx mimetic ebselen. BALF inflammation persisted in GPx-1(-/-) mice on Day 10
      after infection, and GPx-1(-/-) mice had significantly more influenza-specific
      CD8(+) T cells in spleen compared with WT mice (n = 3-4; P < 0.05). Infected GPx
      1(-/-) mice had greater peribronchial and parenchymal inflammation than WT mice,
      and viral titer was significantly reduced in GPx-1(-/-) mice at Day 3 (n = 5; P <
      0.05). Gene expression analysis revealed that infected GPx-1(-/-) mice had higher
      whole lung TNF-alpha, macrophage inflammatory protein (MIP)-1alpha, MIP-2, KC,
      and matrix metalloproteinase (MMP)-12 mRNA compared with infected WT mice. GPx-1(
      /-) mice had more MIP-2 protein in BALF at Day 3 and more active MMP-9 protease
      in BALF at Days 3 and 7 than WT mice. These data indicate that GPx-1 reduces
      influenza A virus-induced lung inflammation.

PMID- 23002099
TI  - Intrapleural adenoviral delivery of human plasminogen activator inhibitor-1
      exacerbates tetracycline-induced pleural injury in rabbits.
AB  - Elevated concentrations of plasminogen activator inhibitor-1 (PAI-1) are
      associated with pleural injury, but its effects on pleural organization remain
      unclear. A method of adenovirus-mediated delivery of genes of interest (expressed
      under a cytomegalovirus promoter) to rabbit pleura was developed and used with
      lacZ and human (h) PAI-1. Histology, beta-galactosidase staining, Western
      blotting, enzymatic and immunohistochemical analyses of pleural fluids (PFs),
      lavages, and pleural mesothelial cells were used to evaluate the efficiency and
      effects of transduction. Transduction was selective and limited to the pleural
      mesothelial monolayer. The intrapleural expression of both genes was transient,
      with their peak expression at 4 to 5 days. On Day 5, hPAI-1 (40-80 and 200-400 nM
      of active and total hPAI-1 in lavages, respectively) caused no overt pleural
      injury, effusions, or fibrosis. The adenovirus-mediated delivery of hPAI-1 with
      subsequent tetracycline-induced pleural injury resulted in a significant
      exacerbation of the pleural fibrosis observed on Day 5 (P = 0.029 and P = 0.021
      versus vehicle and adenoviral control samples, respectively). Intrapleural
      fibrinolytic therapy (IPFT) with plasminogen activators was effective in both
      animals overexpressing hPAI-1 and control animals with tetracycline injury alone.
      An increase in intrapleural active PAI-1 (from 10-15 nM in control animals to 20
      40 nM in hPAI-1-overexpressing animals) resulted in the increased formation of
      PAI-1/plasminogen activator complexes in vivo. The decrease in intrapleural
      plasminogen-activating activity observed at 10 to 40 minutes after IPFT
      correlates linearly with the initial concentration of active PAI-1. Therefore,
      active PAI-1 in PFs affects the outcome of IPFT, and may be both a biomarker of
      pleural injury and a molecular target for its treatment.

PMID- 23002102
TI  - Atomoxetine reduces ADHD symptoms in children with autism spectrum disorder.

PMID- 23002100
TI  - Ozone enhances pulmonary innate immune response to a Toll-like receptor-2
      agonist.
AB  - Previous work demonstrated that pre-exposure to ozone primes innate immunity and
      increases Toll-like receptor-4 (TLR4)-mediated responses to subsequent
      stimulation with LPS. To explore the pulmonary innate immune response to ozone
      exposure further, we investigated the effects of ozone in combination with
      Pam3CYS, a synthetic TLR2/TLR1 agonist. Whole-lung lavage (WLL) and lung tissue
      were harvested from C57BL/6 mice after exposure to ozone or filtered air,
      followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the WLL, the
      surface expression of TLRs on macrophages, and lung RNA genomic expression
      profiles were examined. We demonstrated an increased WLL cell influx, increased
      IL-6 and chemokine KC (Cxcl1), and decreased macrophage inflammatory protein
      (MIP)-1alpha and TNF-alpha in response to Pam3CYS as a result of ozone pre
      exposure. We also observed the increased cell surface expression of TLR4, TLR2,
      and TLR1 on macrophages as a result of ozone alone or in combination with
      Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase
      in the expression of genes related to injury repair and the cell cycle as a
      result of ozone alone or in combination with Pam3CYS. Our results extend previous
      findings with ozone/LPS to other TLR ligands, and suggest that the ozone priming
      of innate immunity is a general mechanism. Gene expression profiling of lung
      tissue identified transcriptional networks and genes that contribute to the
      priming of innate immunity at the molecular level.

PMID- 23002101
TI  - Sex-specific perinatal nicotine-induced asthma in rat offspring.
AB  - Recently, we have suggested that down-regulation of homeostatic mesenchymal
      peroxisome proliferator-activated receptor gamma signaling after in utero
      nicotine exposure might contribute to asthma. Here, we have exploited an in vivo
      rat model of asthma to determine if the effects of perinatal nicotine exposure on
      offspring pulmonary function and mesenchymal markers of airway contractility in
      both tracheal and lung parenchymal tissue are sex specific, and whether the
      protection afforded by the peroxisome proliferator-activated receptor gamma
      agonist, rosiglitazone (RGZ), against the perinatal nicotine-induced effect on
      offspring lung is also sex specific. Pregnant rat dams received placebo,
      nicotine, or nicotine plus RGZ daily from Embryonic Day 6 until Postnatal Day 21,
      at which time lung resistance, compliance, tracheal contractility, and the
      expression of structural and functional mesenchymal markers of pulmonary
      contractility were determined. Compared with control animals, perinatal nicotine
      exposure caused a significant increase in airway resistance and a decrease in
      airway compliance after a methacholine challenge in both male and female
      offspring, with more pronounced changes in the males. In contrast to this, the
      effects of perinatal nicotine exposure on acetylcholine-induced tracheal
      constriction, along with the expression of its mesenchymal markers, were observed
      exclusively in the male offspring. Concomitant treatment with RGZ normalized the
      nicotine-induced alterations in pulmonary function in both sexes, as well as the
      male-specific effects on acetylcholine-induced tracheal constriction, along with
      the affected mesenchymal markers. These data suggest that perinatal nicotine
      exposure causes sex-specific perinatal cigarette smoke exposure-induced asthma,
      providing a powerful phenotypic model for unequivocally determining the
      underlying nature of the cell molecular mechanism for this disease.

PMID- 23002103
TI  - New synthetic prosthesis for peripheral nerve injuries: an experimental pilot
      study.
AB  - INTRODUCTION: Even the most modern technology has failed to induce satisfactory
      functional regeneration of traumatically severed peripheral nerves. Delayed
      neural regeneration and in consequence, slower neural conduction seriously limit
      muscle function in the area supplied by the injured nerve. This study aimed to
      compare a new nerve coaptation system involving an innovative prosthesis with the
      classical clinical method of sutured nerve coaptation. Besides the time and
      degree of nerve regeneration, the influence of electrostimulation was also
      tested. METHODS: The sciatic nerve was severed in 14 female Gottingen minipigs
      with an average weight of 40.4 kg. The animals were randomized into 2 groups: One
      group received the new prosthesis and the other underwent microsurgical
      coaptation. In each group, according to the randomization a part of the animals
      received postoperative electrostimulation. Postoperative monitoring and the
      stimulation schedule covered a period of 9 months, during which axonal budding
      was evaluated monthly. RESULTS: The data from the pilot study indicate that
      results with the nerve prosthesis were comparable with those of conventional
      coaptation. CONCLUSION: The results indicate that implantation of the nerve
      prosthesis allows for good and effective neural regeneration. This new and simple
      treatment option for peripheral nerve injuries can be performed in any hospital
      with surgical facilities as it does not involve the demanding microsurgical
      suture technique that can only be performed in specialized centers.

PMID- 23002104
TI  - The SWI/SNF KlSnf2 subunit controls the glucose signaling pathway to coordinate
      glycolysis and glucose transport in Kluyveromyces lactis.
AB  - In Kluyveromyces lactis, the expression of the major glucose permease gene RAG1
      is controlled by extracellular glucose through a signaling cascade similar to the
      Saccharomyces cerevisiae Snf3/Rgt2/Rgt1 pathway. We have identified a key
      component of the K. lactis glucose signaling pathway by characterizing a new
      mutation, rag20-1, which impairs the regulation of RAG1 and hexokinase RAG5 genes
      by glucose. Functional complementation of the rag20-1 mutation identified the
      KlSNF2 gene, which encodes a protein 59% identical to S. cerevisiae Snf2, the
      major subunit of the SWI/SNF chromatin remodeling complex. Reverse transcription
      quantitative PCR and chromatin immunoprecipitation analyses confirmed that the
      KlSnf2 protein binds to RAG1 and RAG5 promoters and promotes the recruitment of
      the basic helix-loop-helix Sck1 activator. Besides this transcriptional effect,
      KlSnf2 is also implicated in the glucose signaling pathway by controlling Sms1
      and KlRgt1 posttranscriptional modifications. When KlSnf2 is absent, Sms1 is not
      degraded in the presence of glucose, leading to constitutive RAG1 gene repression
      by KlRgt1. Our work points out the crucial role played by KlSnf2 in the
      regulation of glucose transport and metabolism in K. lactis, notably, by
      suggesting a link between chromatin remodeling and the glucose signaling pathway.

PMID- 23002105
TI  - Pseudohyphal growth of Cryptococcus neoformans is a reversible dimorphic
      transition in response to ammonium that requires Amt1 and Amt2 ammonium
      permeases.
AB  - Cryptococcus neoformans is a human-pathogenic basidiomycete that commonly infects
      HIV/AIDS patients to cause meningoencephalitis (7, 19). C. neoformans grows as a
      budding yeast during vegetative growth or as hyphae during sexual reproduction.
      Pseudohyphal growth of C. neoformans has been observed rarely during murine and
      human infections but frequently during coculture with amoeba; however, the
      genetics underlying pseudohyphal growth are largely unknown. Our studies found
      that C. neoformans displays pseudohyphal growth under nitrogen-limiting
      conditions, especially when a small amount of ammonium is available as a sole
      nitrogen source. Pseudohyphal growth was observed with Cryptococcus neoformans
      serotypes A and D and Cryptococcus gattii. C. neoformans pseudohyphae bud to
      produce yeast cells and normal smooth hemispherical colonies when transferred to
      complete media, indicating that pseudohyphal growth is a conditional
      developmental stage. Subsequent analysis revealed that two ammonium permeases
      encoded by the AMT1 and AMT2 genes are required for pseudohyphal growth. Both
      amt1 and amt2 mutants are capable of forming pseudohyphae; however, amt1 amt2
      double mutants do not form pseudohyphae. Interestingly, C. gattii pseudohypha
      formation is irreversible and involves a RAM pathway mutation that drives
      pseudohyphal development. We also found that pseudohyphal growth is related to
      the invasive growth into the medium. These results demonstrate that pseudohyphal
      growth is a common reversible growth pattern in C. neoformans but a mutational
      genetic event in C. gattii and provide new insights into understanding
      pseudohyphal growth of Cryptococcus.

PMID- 23002106
TI  - Differential involvement of beta-glucosidases from Hypocrea jecorina in rapid
      induction of cellulase genes by cellulose and cellobiose.
AB  - Appropriate perception of cellulose outside the cell by transforming it into an
      intracellular signal ensures the rapid production of cellulases by cellulolytic
      Hypocrea jecorina. The major extracellular beta-glucosidase BglI (CEL3a) has been
      shown to contribute to the efficient induction of cellulase genes. Multiple beta
      glucosidases belonging to glycosyl hydrolase (GH) family 3 and 1, however, exist
      in H. jecorina. Here we demonstrated that CEL1b, like CEL1a, was an intracellular
      beta-glucosidase displaying in vitro transglycosylation activity. We then found
      evidence that these two major intracellular beta-glucosidases were involved in
      the rapid induction of cellulase genes by insoluble cellulose. Deletion of cel1a
      and cel1b significantly compromised the efficient gene expression of the major
      cellulase gene, cbh1. Simultaneous absence of BglI, CEL1a, and CEL1b caused the
      induction of the cellulase gene by cellulose to further deteriorate. The
      induction defect, however, was not observed with cellobiose. The absence of the
      three beta-glucosidases, rather, facilitated the induced synthesis of cellulase
      on cellobiose. Furthermore, addition of cellobiose restored the productive
      induction on cellulose in the deletion strains. The results indicate that the
      three beta-glucosidases may not participate in transforming cellobiose beyond
      hydrolysis to provoke cellulase formation in H. jecorina. They may otherwise
      contribute to the accumulation of cellobiose from cellulose as inducing signals.

PMID- 23002107
TI  - The putative guanine nucleotide exchange factor RicA mediates upstream signaling
      for growth and development in Aspergillus.
AB  - Heterotrimeric G proteins (G proteins) govern growth, development, and secondary
      metabolism in various fungi. Here, we characterized ricA, which encodes a
      putative GDP/GTP exchange factor for G proteins in the model fungus Aspergillus
      nidulans and the opportunistic human pathogen Aspergillus fumigatus. In both
      species, ricA mRNA accumulates during vegetative growth and early developmental
      phases, but it is not present in spores. The deletion of ricA results in severely
      impaired colony growth and the total (for A. nidulans) or near (for A. fumigatus)
      absence of asexual sporulation (conidiation). The overexpression (OE) of the A.
      fumigatus ricA gene (AfricA) restores growth and conidiation in the DeltaAnricA
      mutant to some extent, indicating partial conservation of RicA function in
      Aspergillus. A series of double mutant analyses revealed that the removal of RgsA
      (an RGS protein of the GanB Galpha subunit), but not sfgA, flbA, rgsB, or rgsC,
      restored vegetative growth and conidiation in DeltaAnricA. Furthermore, we found
      that RicA can physically interact with GanB in yeast and in vitro. Moreover, the
      presence of two copies or OE of pkaA suppresses the profound defects caused by
      DeltaAnricA, indicating that RicA-mediated growth and developmental signaling is
      primarily through GanB and PkaA in A. nidulans. Despite the lack of conidiation,
      brlA and vosA mRNAs accumulated to normal levels in the DeltaricA mutant. In
      addition, mutants overexpressing fluG or brlA (OEfluG or OEbrlA) failed to
      restore development in the DeltaAnricA mutant. These findings suggest that the
      commencement of asexual development requires unknown RicA-mediated signaling
      input in A. nidulans.

PMID- 23002108
TI  - Sudden oak death: interactions of the exotic oomycete Phytophthora ramorum with
      naive North American hosts.
AB  - Ten years after a threatening and previously unknown disease of oaks and tanoaks
      appeared in coastal California, a significant amount of progress has been made
      toward the understanding of its causal agent Phytophthora ramorum and of the
      novel pathosystems associated with this exotic organism. However, a complete
      understanding of the ecology and epidemiology of this species still eludes us. In
      part, our inability to fully understand this organism is due to its phylogenetic,
      phylogeographic, phenotypic, and epidemiological complexities, all reviewed in
      this paper. Most lines of evidence suggest that the high degree of disease
      severity reported in California is not simply due to a generalized lack of
      resistance or tolerance in naive hosts but also to an innate ability of the
      pathogen to survive in unfavorable climatic conditions and to reproduce rapidly
      when conditions become once again favorable.

PMID- 23002109
TI  - Galectin-1 influences trophoblast immune evasion and emerges as a predictive
      factor for the outcome of pregnancy.
AB  - Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role
      in regulating the maternal immune response against placental alloantigens,
      contributing to pregnancy maintenance. Both decidua and placenta contribute to
      gal-1 expression and may be important for the maternal immune regulation. The
      expression of gal-1 within the placenta is considered relevant to cell-adhesion
      and invasion of trophoblasts, but the role of gal-1 in the immune evasion
      machinery exhibited by trophoblast cells remains to be elucidated. In this study,
      we analyzed gal-1 expression in preimplantation human embryos and first-trimester
      decidua-placenta specimens and serum gal-1 levels to investigate the
      physiological role played by this lectin during pregnancy. The effect on human
      leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of
      gal-1 was also determined in the human invasive, proliferative extravillous
      cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women,
      circulating gal-1 levels were significantly decreased in patients who
      subsequently suffered a miscarriage. Human embryos undergoing preimplantation
      development expressed gal-1 on the trophectoderm and inner cell mass.
      Furthermore, our in vitro experiments showed that exogenous gal-1 positively
      regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells,
      whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5
      and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal
      immune regulation by modulating HLA-G expression on trophoblast cells.
      Circulating gal-1 levels could serve as a predictive factor for pregnancy success
      in early human gestation.

PMID- 23002110
TI  - The maternal HLA-G 1597DeltaC null mutation is associated with increased risk of
      pre-eclampsia and reduced HLA-G expression during pregnancy in African-American
      women.
AB  - The non-classical major histocompatibility complex molecule, human leukocyte
      antigen (HLA)-G, is thought to contribute to maternal immune tolerance and
      successful placentation during pregnancy. Genetic polymorphisms in HLA-G are
      known to influence expression levels as well as the relative expression of
      individual protein isoforms. As diminished or aberrant HLA-G expression patterns
      may contribute to the development of certain pregnancy complications, we sought
      to investigate the association between functional HLA-G polymorphisms and the
      risk of pre-eclampsia (PE) in African-American women. The association between
      maternal and fetal genotype at six HLA-G polymorphisms and risk of PE was
      assessed in 372 pregnancies (314 normotensive; 58 pre-eclamptic). We observed an
      elevated risk of PE (P = 0.00027) in pregnancies where the mother carried the
      1597DeltaC allele, a null allele that abolishes expression of full-length HLA-G
      isoforms. Furthermore, the frequency of the maternal 1597DeltaC allele was
      highest in the subset of pre-eclamptic pregnancies that were delivered preterm,
      suggesting an association between the null allele and the severity of PE. We then
      replicated the association between higher maternal 1597DeltaC allele frequency
      and increased severity of PE (P = 0.038) in an independent sample of 533 African
      American women. Finally, to investigate the mechanistic basis of this
      association, we measured circulating soluble HLA-G (sHLA-G) concentrations in
      maternal serum collected during pregnancy in 51 healthy, normotensive African
      American control women and found significantly lower levels in women carrying the
      1597DeltaC allele (P = 0.012). These results demonstrate that maternal HLA-G
      genotype is significantly associated with risk of PE in African-American women
      and is predictive of circulating sHLA-G levels during pregnancy.

PMID- 23002111
TI  - Overcoming challenges to achieving meaningful use: insights from hospitals that
      successfully received Centers for Medicare and Medicaid Services payments in
      2011.
AB  - OBJECTIVE: In an effort to understand better the federal electronic health record
      (EHR) incentive programme's challenges, this study compared hospitals that did
      and did not receive meaningful use (MU) payments in the programme's first year
      based on the challenges they anticipated a year before. MATERIALS AND METHODS:
      This cross-sectional study used 2010 American Hospital Association survey data
      and 2011 Centers for Medicare and Medicaid Services data that identify hospitals
      receiving MU payments. Multivariate regression analysis assessed differences in
      2010 anticipated challenges to MU for hospitals that were successful in earning
      2011 MU payment compared to hospitals that intended to participate in the
      programme but were not yet successful. RESULTS: The study sample consisted of
      2475 hospitals, 313 of which received MU payments in 2011. Controlling for
      standard hospital characteristics, hospitals that reported the computerized
      provider order entry (CPOE) MU criterion as a primary challenge were 18% less
      likely to receive a 2011 MU payment compared to hospitals that reported other
      criteria as primary challenges. DISCUSSION: CPOE was the main challenge among
      hospitals that failed to achieve MU in the first year of the programme. In order
      to maximize the incentive programme's effectiveness, policymakers, healthcare
      organizations, and EHR vendors may benefit from increased attention to hospitals'
      challenges with CPOE. CONCLUSION: As the EHR incentive programme matures,
      policymakers and other stakeholders should consider strategies that maintain the
      critical elements of MU while adequately supporting hospitals that desire to
      become MU but are impeded by specific technological, cultural, and organizational
      adoption and use challenges.

PMID- 23002112
TI  - Longer duration of exclusive breastfeeding associated with reduced risk of
      childhood asthma up to age six.

PMID- 23002113
TI  - Gastrointestinal dysfunction in Chinese patients with fat-phobic and nonfat
      phobic anorexia nervosa.
AB  - Although gastrointestinal and other somatic symptoms are common in patients with
      anorexia nervosa (AN), and a growing cross-national literature indicates that not
      all anorexic patients exhibit the core diagnostic symptom of fat phobia, the
      relationship between somatic symptoms and anorexic illness remains unclear. Our
      objective was to evaluate gastrointestinal dysfunction (GD) in Chinese patients
      with fat phobic (FP) and nonfat phobic (NFP) anorexia nervosa. A total of 113 FP-
      and 28 NFP-AN outpatients underwent standardized clinical assessment and
      completed a new 8-item GD scale and other psychopathological measures. A majority
      (79.4%) of AN patients reported at least some gastrointestinal complaints on the
      GD scale (Cronbach's alpha = 0.78). FP-AN patients scored significantly higher
      than NFP-AN patients. The FP-AN with high GD group reported a higher level of
      specific and general psychopathology than the FP- and NFP-AN with low GD groups.
      Contrary to expectations, gastrointestinal symptoms were more common in FP-AN
      than NFP-AN patients. FP-AN with high GD was more severe than FP- and NFP-AN with
      low GD. The current fat phobic conceptualization of the anorexic illness may
      overlook its phenomenologic heterogeneity and reify a dichotomy that is
      inconsistent with patients' varied experience of food restriction.

PMID- 23002114
TI  - Response to cardiac resynchronization therapy in elderly patients (>=70 years)
      and octogenarians.
AB  - AIMS: Cardiac resynchronization therapy (CRT) leads to reverse ventricular
      remodelling, improved functional capacity, and better clinical outcome in
      patients with advanced chronic heart failure, reduced ejection fraction, and
      evidence of ventricular conduction delay, who are under optimal medical therapy.
      This study investigated whether these benefits can be extrapolated to older
      patients, typically not included in randomized clinical trials. METHODS AND
      RESULTS: Consecutive patients who received a CRT device between October 2008 and
      June 2011, including optimization afterwards in a dedicated clinic, were
      stratified into 3 pre-specified groups, according to age: <70 years (n = 76); 70
      79 years (n = 95); and >=80 years (n = 49). Left ventricular remodelling,
      functional capacity, heart failure hospitalization, and mortality data were
      assessed during follow-up. Reverse left ventricular remodelling and improvement
      in New York Heart Association functional class were similar in all groups at 6
      months after implantation. During mean follow-up of 20 months, 32 patients died
      and 66 were admitted for heart failure. Annualized mortality rates were
      significantly higher in elderly patients (6% vs. 8% vs. 15% in all groups,
      respectively; P < 0.001), but time to death or first heart failure admission was
      similar among age groups (P = 0.531). Progressive pump failure was the major
      cause of death (50%), with co-morbidity-related deaths also being frequent (41%).
      CONCLUSION: Reverse left ventricular remodelling and functional capacity
      improvement after CRT are sustained at advanced age. Moreover, time to all-cause
      mortality or heart failure admission was similar, irrespective of age, in a
      context of maximized optimization including optimal medical therapy.

PMID- 23002115
TI  - The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet alpha
      granule biogenesis.
AB  - Patients with platelet alpha or dense delta-granule defects have bleeding
      problems. Although several proteins are known to be required for delta-granule
      development, less is known about alpha-granule biogenesis. Our previous work
      showed that the BEACH protein NBEAL2 and the Sec1/Munc18 protein VPS33B are
      required for alpha-granule biogenesis. Using a yeast two-hybrid screen, mass
      spectrometry, coimmunoprecipitation, and bioinformatics studies, we identified
      VPS16B as a VPS33B-binding protein. Immunoblotting confirmed VPS16B expression in
      various human tissues and cells including megakaryocytes and platelets, and also
      in megakaryocytic Dami cells. Characterization of platelets from a patient with
      arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome containing
      mutations in C14orf133 encoding VPS16B revealed pale-appearing platelets in blood
      films and electron microscopy revealed a complete absence of alpha-granules,
      whereas delta-granules were observed. Soluble and membrane-bound alpha-granule
      proteins were reduced or undetectable, suggesting that both releasable and
      membrane-bound alpha-granule constituents were absent. Immunofluorescence
      microscopy of Dami cells stably expressing GFP-VPS16B revealed that similar to
      VPS33B, GFP-VPS16B colocalized with markers of the trans-Golgi network, late
      endosomes and alpha-granules. We conclude that VPS16B, similar to its binding
      partner VPS33B, is essential for megakaryocyte and platelet alpha-granule
      biogenesis.

PMID- 23002116
TI  - Evaluation of participants with suspected heritable platelet function disorders
      including recommendation and validation of a streamlined agonist panel.
AB  - Light transmission aggregometry (LTA) is used worldwide for the investigation of
      heritable platelet function disorders (PFDs), but interpretation of results is
      complicated by the feedback effects of ADP and thromboxane A(2) (TxA(2)) and by
      the overlap with the response of healthy volunteers. Over 5 years, we have
      performed lumi-aggregometry on 9 platelet agonists in 111 unrelated research
      participants with suspected PFDs and in 70 healthy volunteers. Abnormal LTA or
      ATP secretion test results were identified in 58% of participants. In 84% of
      these, the patterns of response were consistent with defects in Gi receptor
      signaling, the TxA(2) pathway, and dense granule secretion. Participants with
      defects in signaling to Gq-coupled receptor agonists and to collagen were also
      identified. Targeted genotyping identified 3 participants with function
      disrupting mutations in the P2Y(12) ADP and TxA(2) receptors. The results of the
      present study illustrate that detailed phenotypic analysis using LTA and ATP
      secretion is a powerful tool for the diagnosis of PFDs. Our data also enable
      subdivision at the level of platelet-signaling pathways and in some cases to
      individual receptors. We further demonstrate that most PFDs can be reliably
      diagnosed using a streamlined panel of key platelet agonists and specified
      concentrations suitable for testing in most clinical diagnostic laboratories.

PMID- 23002117
TI  - A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete
      remission.
AB  - IPH2101 is an anti-killer inhibitory receptor (anti-KIR) mAb that can block KIR
      mediated inhibition of natural killer (NK) cells to enhance cytotoxicity against
      acute myeloid leukemia blasts. We have conducted a phase 1 study of IPH2101 in
      elderly patients with acute myeloid leukemia in first complete remission.
      Patients received escalating doses (0.0003-3 mg/kg) of IPH2101 following a 3 + 3
      design. Safety, toxicity (primary end points), pharmacokinetics, outcome, and
      immunologic correlates were evaluated. Twenty-three patients (median age, 71
      years), were enrolled. Adverse events were mild and transient, consisting mainly
      of infusion syndrome and erythema. The maximum tolerated dose was not reached,
      although full KIR saturation (> 90%) was sustained for more than 2 weeks at 1 and
      3 mg/kg. There was a clear correlation between mAb exposure and KIR occupancy.
      Neither hematologic toxicity nor significant changes in the numbers and
      distribution of lymphocyte subsets, NK cell receptor expression, or in vitro
      cytotoxicity were seen. At the highest dose levels (0.3, 1, and 3 mg/kg),
      transient increases in TNF-alpha and MIP-1beta serum concentrations and NK cell
      CD69 expression were observed. Overall and relapse-free survival in the present
      study compared favorably to reports in comparable patient populations. We
      conclude that IPH2101 administration is safe and can block KIR for prolonged
      periods of time with limited side effects. Registered with the European Union
      Drug Regulating Authorities Clinical Trials (EUDRACT) as 2005-005298-31.

PMID- 23002118
TI  - Zinc-finger nuclease-mediated correction of alpha-thalassemia in iPS cells.
AB  - Induced pluripotent stem (iPS) cell technology holds vast promises for a cure to
      the hemoglobinopathies. Constructs and methods to safely insert therapeutic genes
      to correct the genetic defect need to be developed. Site-specific insertion is a
      very attractive method for gene therapy because the risks of insertional
      mutagenesis are eliminated provided that a "safe harbor" is identified, and
      because a single set of validated constructs can be used to correct a large
      variety of mutations simplifying eventual clinical use. We report here the
      correction of alpha-thalassemia major hydrops fetalis in transgene-free iPS cells
      using zinc finger-mediated insertion of a globin transgene in the AAVS1 site on
      human chromosome 19. Homozygous insertion of the best of the 4 constructs tested
      led to complete correction of globin chain imbalance in erythroid cells
      differentiated from the corrected iPS cells.

PMID- 23002120
TI  - Work effort, productivity, and compensation trends in members of the Society for
      Vascular Surgery.
AB  - OBJECTIVE: To survey the Society for Vascular Surgery (SVS) membership with
      regard to type of practice, employment status, work effort, and productivity
      criteria. METHODS: A survey questionnaire was developed to gather information
      about member demographics, academic versus private practice, employment status,
      time in practice, measures of work, and productivity criteria. RESULTS: Two
      thirds of members were in private practice, 24% were employed by hospitals/health
      systems and 21% were in solo practice. Only 50.3% said they or their group kept
      record of relative value units/work relative value units (RVUs/WRVUs). Of those
      tracking RVUs, significantly greater number of private practice VS reported
      annual RVUs >10,000 compared to academic VS (P < .01). Net collections were the
      most common measure of productivity (51%) followed by WRVUs (36%). CONCLUSIONS:
      With a changing environment and employment status of VS, tracking measures of
      productivity and proper benchmarking become vitally important. The SVS should
      consider positioning itself to collect, store, manage, and provide such
      information to assist members in practice transition.

PMID- 23002121
TI  - Impact of an assistant on the technical skills of the primary operator in
      superficial femoral artery angioplasty.
AB  - OBJECTIVE: To assess the impact of an assistant on the technical skills of the
      operator performing superficial femoral artery (SFA) angioplasty on the vascular
      intervention simulation trainer (VIST) simulator. METHODS: Eight experts
      performed 2 SFA angioplasties each on the VIST. Four experts had an assistant
      available. Experts' video recordings were blindly evaluated using global and
      procedural rating scales. RESULTS: Experts with assistants scored higher than the
      controls in the first: global rating scale (47.8 +/- 0.5 vs 33.5 +/- 5.1, P =
      .01); procedural rating scale (94.3 +/- 2.2 vs 89 +/- 2.5, P = .02) and the
      second procedure: global rating scale (47.8 +/- 0.5 vs 38 +/- 7, P = .03);
      procedural rating scale (95.3 +/- 0.5 vs 89.5 +/- 2.4, P = .02). CONCLUSIONS: The
      presence of an assistant had a positive influence on the technical skills of the
      operator performing SFA angioplasty on the VIST simulator.

PMID- 23002119
TI  - IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not
      UNC-93B-deficient patients.
AB  - We studied the distribution of peripheral B-cell subsets in patients deficient
      for key factors of the TLR-signaling pathways (MyD88, TIRAP/MAL, IL-1 receptor
      associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which
      signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their
      function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10)
      require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper
      localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that
      IgM(+)IgD(+)CD27(+) but not switched B cells were strongly reduced in MyD88-,
      IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be
      compensated with age. However, somatic hypermutation of Ig genes and heavy-chain
      CDR3 size distribution of IgM(+)IgD(+)CD27(+) B cells were not affected in these
      patients. In contrast, the numbers of IgM(+)IgD(+)CD27(+) B cells were normal in
      the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B-dependent TLRs,
      and notably TLR9, are dispensable for the presence of this subset in peripheral
      blood. Interestingly, TLR10 was found to be expressed at greater levels in
      IgM(+)IgD(+)CD27(+) compared with switched B cells in healthy patients. Hence, we
      propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the
      development and/or maintenance of IgM(+)IgD(+)CD27(+) B cells in humans.

PMID- 23002122
TI  - Genetic interactions of hypomorphic mutations in the m7G cap-binding pocket of
      yeast nuclear cap binding complex: an essential role for Cbc2 in meiosis via
      splicing of MER3 pre-mRNA.
AB  - Nuclear cap binding protein complex (CBC) is a heterodimer of a small subunit
      (Cbc2 in yeast) that binds the m(7)G cap and a large subunit (Sto1 in yeast) that
      interacts with karyopherins. In order to probe the role of cap recognition in
      yeast CBC function, we introduced alanine mutations (Y24A, F91A, D120A, D122A,
      R129A, and R133A) and N-terminal deletions (NDelta21 and NDelta42) in the cap
      binding pocket of Cbc2. These lesions had no effect on vegetative growth, but
      they ameliorated the cold-sensitivity of tgs1Delta cells that lack
      trimethylguanosine caps (a phenotype attributed to ectopic association of CBC
      with the m(7)G cap of the normally TMG-capped U1 snRNA), thereby attesting to
      their impact on cap binding in vivo. Further studies of the Cbc2-Y24A variant
      revealed synthetic lethality or sickness with null mutations of proteins involved
      in early steps of spliceosome assembly (Nam8, Mud1, Swt21, Mud2, Ist3, and Brr1)
      and with otherwise benign mutations of Msl5, the essential branchpoint binding
      protein. Whereas the effects of weakening CBC-cap interactions are buffered by
      other actors in the splicing pathway during mitotic growth, the NDelta42 allele
      causes a severe impediment to yeast sporulation and meiosis. RNA analysis
      revealed a selective defect in the splicing of MER3 and SAE3 transcripts in cbc2
      NDelta42 diploids during attempted sporulation. An intronless MER3 cDNA fully
      restored sporulation and spore viability in the cbc2-NDelta42 strain, signifying
      that MER3 splicing is a limiting transaction. These studies reveal a new level of
      splicing control during meiosis that is governed by nuclear CBC.

PMID- 23002123
TI  - Impact of base pair identity 5' to the spliceosomal branch site adenosine on
      branch site conformation.
AB  - The branch site helix from Saccharomyces cerevisiae with pseudouridine (psi)
      incorporated in a phylogenetically conserved position of U2 snRNA features an
      extrahelical branch site adenosine (A) that forms a base triple interaction with
      the minor groove edge of a widely conserved purine(U2 strand)-pyrimidine(intron
      strand) (R(U2)-Y(intron)) base pair two positions upstream. In these studies, NMR
      spectra of a duplex in which 2-aminopurine (2ap), a fluorescent analog of adenine
      lacking the proposed hydrogen bond donor, was substituted for the branch site A,
      indicated that the substitution does not alter the extrahelical position of the
      branch site residue; thus, it appears that a hydrogen bond between the adenine
      amino group and the R-Y pair is not obligatory for stabilization of the
      extrahelical conformation. In contrast, reversal of the orientation of A(U2)
      U(intron) to U(U2)-A(intron) resulted in an intrahelical position for the branch
      site A or 2ap. Fluorescence intensity of 2ap substituted for the branch site A
      with the original R(U2)-Y(intron) orientation (AU or GC) was high, consistent
      with an extrahelical position, whereas fluorescence in helices with the reversed
      R-Y orientation, or with a mismatched pair (A-U -> G*A or U*C), was markedly
      quenched, implying that the residue was stacked in the helix. The A 5' to the
      branch site residue was not extrahelical in any of the duplexes. These findings
      suggest that the R(U2)-Y(intron) base pair orientation in the psi-dependent
      branch site helix plays an important role in positioning the branch site A for
      recognition and/or function.

PMID- 23002124
TI  - U.S. Food and Drug Administration Approval: peginterferon-alfa-2b for the
      adjuvant treatment of patients with melanoma.
AB  - On March 29, 2011, the U.S. Food and Drug Administration approved peginterferon
      alfa-2b (PEG-IFN) (SylatronTM; Schering Corporation, Kenilworth, NJ) for the
      adjuvant treatment of melanoma patients with microscopic or gross nodal
      involvement following definitive surgical resection including complete
      lymphadenectomy. The approval was based on a single, open-label, multicenter
      trial enrolling 1,256 patients. After surgical resection, patients were
      randomized (1:1) to either PEG-IFN or observation for 5 years. PEG-IFN, 6 MUg/kg
      per week, was administered s.c. for eight doses, followed by 3 MUg/kg per week
      for up to 252 weeks. Stratification factors included microscopic or gross nodal
      involvement, number of positive nodes, Breslow thickness, ulceration, sex, and
      study center. Patients were assessed for recurrence by the investigators based on
      physical examination every 3 months for 2 years and every 6 months thereafter.
      The relapse-free survival (RFS) interval, the primary efficacy endpoint, was
      significantly longer in PEG-IFN-treated patients. The median RFS times were 34.8
      months and 25.5 months, respectively. There was no statistically significant
      difference in the overall survival time. The most common (>60%) grade 1-4 adverse
      reactions were fatigue, increased alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), pyrexia, headache, anorexia, myalgia, nausea, chills, and
      injection site reactions. The most common serious adverse reactions were fatigue,
      increased ALT and AST, and pyrexia. Thirty-three percent of patients receiving
      PEG-IFN discontinued treatment as a result of adverse reactions. Five deaths were
      reported within 30 days of the last treatment dose, two resulting from
      cardiovascular disease considered as possibly related to treatment.

PMID- 23002125
TI  - Pegylated interferon for the adjuvant treatment of melanoma: FDA approved, but
      what is its role?

PMID- 23002127
TI  - Patient power needs to be built on strong intellectual foundations: an essay by
      Nigel Crisp.

PMID- 23002126
TI  - A randomized feasibility study of docetaxel versus vinorelbine in advanced breast
      cancer.
AB  - BACKGROUND: Docetaxel and vinorelbine have demonstrated efficacy in the treatment
      of metastatic breast cancer (MBC). This prospective feasibility study compared
      the efficacy of these two treatments in MBC. METHODS: Patients with MBC
      progressing following anthracycline treatment were randomly assigned to either
      docetaxel (100 mg/m(2)day 1 q3W) or vinorelbine (25mg/m(2) day 1 q2W). Patients
      were eligible to cross over at progression. Objective response rates (ORR), time
      to progression (TTP) and overall survival (OS) were measured. RESULTS: 37
      patients were randomised. 2 patients were excluded due to protocol violations. Of
      35 remaining patients 17 received docetaxel and 18 received vinorelbine per
      protocol. ORR was 12.5% and 6.0% respectively for docetaxel and vinorelbine. The
      median time to progression was 10.4 weeks (range 6-14 weeks) in docetaxel arm and
      7.6 weeks (range 4-11 weeks) in vinorelbine arm (p = .82). The clinical benefit
      rate (defined as complete response, partial response plus stable disease) was 44%
      in the docetaxel arm and 12% in the vinorelbine arm. Based on intent to treat the
      median OS in the docetaxel arm was 34 weeks (95% CI, 20.7-48) and 21.2 weeks (95%
      CI, 17-25.4) in vinorelbine arm (p = .388). 16 patients crossed over, 5 from
      docetaxel to vinorelbine and 11 from vinorelbine to docetaxel. At cross over the
      ORR was 0% and 18% on cross over to vinorelbine and docetaxel respectively with a
      median TTP of 17.3 weeks (95% CI, 16.3-18.1) and 18.7 weeks (95% CI, 13.9-23.4)
      for those receiving vinorebine and docetaxel at cross over respectively.
      Vinorelbine however was much better tolerated with fewer grade 3-4 toxicity
      events (n = 4) than docetaxel (n = 27). DISCUSSION: While docetaxel resulted in a
      longer TTP and OS in this study it did not reach statistical significance. TTP
      duration for those patients who crossed over was similar, but overwhelmingly
      vinorelbine had fewer significant grade 3-4 toxicities than docetaxel. Only two
      previous randomized studies have compared the efficacy of single agent docetaxel
      and vinorelbine following prior anthracycline exposure, one in an unselected
      population [16], and the other, HERNATA, in HER2 positive disease with
      trastuzumab used in both arms [17]. The patients randomized in this study were
      relatively heavily pretreated with the majority having received 2-3 lines of
      prior treatment for their metastatic disease. The lower response rates with
      vinorelbine as compared to docetaxel in this study concur with results reported
      in other studies [16]. However, the numbers in both this study and the other
      unselected study [16] are small and need to be interpreted with caution. With
      regard to toxicity, in the present study, grade 3-4 hematological adverse events
      and infection were tenfold greater with docetaxel as compared with vinorelbine,
      consistent with results in HERNATA [17]. While others have reported a
      significantly higher number of overall grade 3-4 toxicities with vinorelbine
      [16], the fact that, as in HERNATA, discontinuations due to toxicities in that
      study [16] were significantly greater with docetaxel as compared to vinorelbine
      suggests either the toxicity data collected did not reflect the true toxicities
      on treatment or that docetaxel toxicities were in some way more severe or
      protracted leading to more numerous discontinuations [16]. Larger randomized
      studies are needed to determine (1) the efficacy of docetaxel versus vinorelbine
      in anthracycline pretreated disease and (2) the efficacy of vinorelbine after
      prior taxane exposure, and particularly how it may compares both with regard to
      efficacy and tolerability with other possible regimens that may utilized such as
      carboplatin-gemcitabine [20] or eribulin [21]. The longer as well as comparable
      TTP at cross over for both agents compared to that upfront suggests there may be
      enrichment at cross over of a group of patients who are not only fit for further
      treatment but are more likely to a derive continued benefit from additional
      treatment.

PMID- 23002128
TI  - How to move to a palliative approach to care for people with multimorbidity.

PMID- 23002129
TI  - Variations in collecting data on central line infections make comparison of
      hospitals impossible, say researchers.

PMID- 23002130
TI  - Number of NHS organisations in the red doubled last year, finds Audit Commission.

PMID- 23002131
TI  - One in three cases of cancer in patients over 70 are diagnosed at emergency
      admission.

PMID- 23002132
TI  - Opportunistic screening for familial hypercholesterolaemia via a community
      laboratory.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) is an inherited disorder
      characterized by increased serum low-density lipoprotein (LDL)-cholesterol
      concentrations and premature atherosclerotic cardiovascular disease. The majority
      of people with FH are currently undiagnosed. We sought to determine the ability
      of a community laboratory to screen for individuals with potential FH. METHODS:
      Serum LDL-cholesterol concentrations issued by a private community laboratory in
      Western Australia were reviewed over a one-year period (1 May 2010 to 31 April
      2011). We assessed the prevalence of possible FH based on LDL-cholesterol
      thresholds employed by the Make Early Diagnosis-Prevent Early Death (MED-PED),
      the Simon Broome Registry and the Dutch Lipid Clinic Network criteria. RESULTS:
      During this period, 84,823 people had 99,467 serum LDL-cholesterol measurements,
      with 91.8% requested by general practitioners. A secondary cause of
      hypercholesterolaemia was identified in 8.3% of subjects with an LDL-cholesterol
      >=5.0 mmol/L. The prevalence of FH based on an LDL-cholesterol >=6.5 mmol/L, the
      99.75th percentile, was 1:398 in this sample population; similarly, the MED-PED
      LDL-cholesterol criteria gave a prevalence of 1:482. CONCLUSIONS: The community
      laboratory is well placed to screen opportunistically for subjects with potential
      FH. This may be achieved using either the MED-PED criteria or a serum LDL
      cholesterol cut-off point of >=6.5 mmol/L, irrespective of age. Further
      investigation is required to determine the most effective method of identifying
      these individuals and, thereby, ensuring referral to a specialist lipid clinic.

PMID- 23002133
TI  - Reliability of plasma fibroblast growth factor 23 as risk biomarker in
      epidemiological studies measured over a four-month period.
AB  - BACKGROUND: Identified as a biomarker of altered calcium-phosphorus metabolism in
      chronic kidney disease, fibroblast growth factor 23 (FGF-23) can also be used as
      a biomarker of risk for cardiovascular disease in the general population.
      However, it is crucial to first evaluate the reproducibility (reliability) of
      plasma FGF-23 concentrations. METHODS: We assessed the reliability of plasma FGF
      23 concentrations using replicate blood samples taken four months apart of 207
      participants from the European Prospective Investigation into Cancer and
      Nutrition-Potsdam Study. RESULTS: Plasma FGF-23 concentrations at baseline
      (geometric mean: 24.7 RU/mL; 95% confidence interval [CI] in RU/mL: 21.8-27.9)
      were not significantly different from those measured four months later (geometric
      mean: 23.7 RU/mL; 95% CI in RU/mL: 20.6-27.1; P = 0.42). The intraclass
      correlation coefficients were 0.69 (95% CI: 0.62-0.76) for all; 0.64 (95% CI:
      0.50-0.75) for men and 0.73 (95% CI: 0.64-0.81) for women. CONCLUSIONS: Plasma
      FGF-23 concentrations showed good reliability over time. Our findings suggest
      that in epidemiological studies, a single plasma FGF-23 measurement may be
      sufficient to derive the relative risk in prospective cohort studies.

PMID- 23002136
TI  - LINE1 family member is negative regulator of HLA-G expression.
AB  - Class Ia molecules of human leucocyte antigen (HLA-A, -B and -C) are widely
      expressed and play a central role in the immune system by presenting peptides
      derived from the lumen of the endoplasmic reticulum. In contrast, class Ib
      molecules such as HLA-G serve novel functions. The distribution of HLA-G is
      mostly limited to foetal trophoblastic tissues and some tumour tissues. The
      mechanism required for the tissue-specific regulation of the HLA-G gene has not
      been well understood. Here, we investigated the genomic regulation of HLA-G by
      manipulating one copy of a genomic DNA fragment on a human artificial chromosome.
      We identified a potential negative regulator of gene expression in a sequence
      upstream of HLA-G that overlapped with the long interspersed element (LINE1);
      silencing of HLA-G involved a DNA secondary structure generated in LINE1. The
      presence of a LINE1 gene silencer may explain the limited expression of HLA-G
      compared with other class I genes.

PMID- 23002134
TI  - Histone H2A variants in nucleosomes and chromatin: more or less stable?
AB  - In eukaryotes, DNA is organized together with histones and non-histone proteins
      into a highly complex nucleoprotein structure called chromatin, with the
      nucleosome as its monomeric subunit. Various interconnected mechanisms regulate
      DNA accessibility, including replacement of canonical histones with specialized
      histone variants. Histone variant incorporation can lead to profound chromatin
      structure alterations thereby influencing a multitude of biological processes
      ranging from transcriptional regulation to genome stability. Among core histones,
      the H2A family exhibits highest sequence divergence, resulting in the largest
      number of variants known. Strikingly, H2A variants differ mostly in their C
      terminus, including the docking domain, strategically placed at the DNA
      entry/exit site and implicated in interactions with the (H3-H4)(2)-tetramer
      within the nucleosome and in the L1 loop, the interaction interface of H2A-H2B
      dimers. Moreover, the acidic patch, important for internucleosomal contacts and
      higher-order chromatin structure, is altered between different H2A variants.
      Consequently, H2A variant incorporation has the potential to strongly regulate
      DNA organization on several levels resulting in meaningful biological output.
      Here, we review experimental evidence pinpointing towards outstanding roles of
      these highly variable regions of H2A family members, docking domain, L1 loop and
      acidic patch, and close by discussing their influence on nucleosome and higher
      order chromatin structure and stability.

PMID- 23002137
TI  - Conformational transitions regulate the exposure of a DNA-binding domain in the
      RuvBL1-RuvBL2 complex.
AB  - RuvBL1 and RuvBL2, also known as Pontin and Reptin, are AAA+ proteins essential
      in small nucleolar ribonucloprotein biogenesis, chromatin remodelling, nonsense
      mediated messenger RNA decay and telomerase assembly, among other functions. They
      are homologous to prokaryotic RuvB, forming single- and double-hexameric rings;
      however, a DNA binding domain II (DII) is inserted within the AAA+ core. Despite
      their biological significance, questions remain regarding their structure. Here,
      we report cryo-electron microscopy structures of human double-ring RuvBL1-RuvBL2
      complexes at ~15 A resolution. Significantly, we resolve two coexisting
      conformations, compact and stretched, by image classification techniques.
      Movements in DII domains drive these conformational transitions, extending the
      complex and regulating the exposure of DNA binding regions. DII domains connect
      with the AAA+ core and bind nucleic acids, suggesting that these conformational
      changes could impact the regulation of RuvBL1-RuvBL2 containing complexes. These
      findings resolve some of the controversies in the structure of RuvBL1-RuvBL2 by
      revealing a mechanism that extends the complex by adjustments in DII.

PMID- 23002135
TI  - Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression
      of selected target genes.
AB  - Despite significant advances made in epigenetic research in recent decades, many
      questions remain unresolved, especially concerning cause and consequence of
      epigenetic marks with respect to gene expression modulation (GEM). Technologies
      allowing the targeting of epigenetic enzymes to predetermined DNA sequences are
      uniquely suited to answer such questions and could provide potent (bio)medical
      tools. Toward the goal of gene-specific GEM by overwriting epigenetic marks
      (Epigenetic Editing, EGE), instructive epigenetic marks need to be identified and
      their writers/erasers should then be fused to gene-specific DNA binding domains.
      The appropriate epigenetic mark(s) to change in order to efficiently modulate
      gene expression might have to be validated for any given chromatin context and
      should be (mitotically) stable. Various insights in such issues have been
      obtained by sequence-specific targeting of epigenetic enzymes, as is presented in
      this review. Features of such studies provide critical aspects for further
      improving EGE. An example of this is the direct effect of the edited mark versus
      the indirect effect of recruited secondary proteins by targeting epigenetic
      enzymes (or their domains). Proof-of-concept of expression modulation of an
      endogenous target gene is emerging from the few EGE studies reported. Apart from
      its promise in correcting disease-associated epi-mutations, EGE represents a
      powerful tool to address fundamental epigenetic questions.

PMID- 23002138
TI  - Reconstructing dynamic gene regulatory networks from sample-based transcriptional
      data.
AB  - The current method for reconstructing gene regulatory networks faces a dilemma
      concerning the study of bio-medical problems. On the one hand, static approaches
      assume that genes are expressed in a steady state and thus cannot exploit and
      describe the dynamic patterns of an evolving process. On the other hand,
      approaches that can describe the dynamical behaviours require time-course data,
      which are normally not available in many bio-medical studies. To overcome the
      limitations of both the static and dynamic approaches, we propose a dynamic
      cascaded method (DCM) to reconstruct dynamic gene networks from sample-based
      transcriptional data. Our method is based on the intra-stage steady-rate
      assumption and the continuity assumption, which can properly characterize the
      dynamic and continuous nature of gene transcription in a biological process. Our
      simulation study showed that compared with static approaches, the DCM not only
      can reconstruct dynamical network but also can significantly improve network
      inference performance. We further applied our method to reconstruct the dynamic
      gene networks of hepatocellular carcinoma (HCC) progression. The derived HCC
      networks were verified by functional analysis and network enrichment analysis.
      Furthermore, it was shown that the modularity and network rewiring in the HCC
      networks can clearly characterize the dynamic patterns of HCC progression.

PMID- 23002139
TI  - Along signal paths: an empirical gene set approach exploiting pathway topology.
AB  - Gene set analysis using biological pathways has become a widely used statistical
      approach for gene expression analysis. A biological pathway can be represented
      through a graph where genes and their interactions are, respectively, nodes and
      edges of the graph. From a biological point of view only some portions of a
      pathway are expected to be altered; however, few methods using pathway topology
      have been proposed and none of them tries to identify the signal paths, within a
      pathway, mostly involved in the biological problem. Here, we present a novel
      algorithm for pathway analysis clipper, that tries to fill in this gap. clipper
      implements a two-step empirical approach based on the exploitation of graph
      decomposition into a junction tree to reconstruct the most relevant signal path.
      In the first step clipper selects significant pathways according to statistical
      tests on the means and the concentration matrices of the graphs derived from
      pathway topologies. Then, it identifies within these pathways the signal paths
      having the greatest association with a specific phenotype. We test our approach
      on simulated and two real expression datasets. Our results demonstrate the
      efficacy of clipper in the identification of signal transduction paths totally
      coherent with the biological problem.

PMID- 23002140
TI  - Structural insight of a concentration-dependent mechanism by which YdiV inhibits
      Escherichia coli flagellum biogenesis and motility.
AB  - YdiV is a negative regulator of cell motility. It interacts with FlhD(4)C(2)
      complex, a product of flagellar master operon, which works as the transcription
      activator of all other flagellar operons. Here, we report the crystal structures
      of YdiV and YdiV(2)-FlhD(2) complex at 1.9 A and 2.9 A resolutions, respectively.
      Interestingly, YdiV formed multiple types of complexes with FlhD(4)C(2). YdiV(1)
      FlhD(4)C(2) and YdiV(2)-FlhD(4)C(2) still bound to DNA, while YdiV(3)-FlhD(4)C(2)
      and YdiV(4)-FlhD(4)C(2) did not. DNA bound FlhD(4)C(2) through wrapping around
      the FlhC subunit rather than the FlhD subunit. Structural analysis showed that
      only two peripheral FlhD subunits were accessible for YdiV binding, forming the
      YdiV(2)-FlhD(4)C(2) complex without affecting the integrity of ring-like
      structure. YdiV(2)-FlhD(2) structure and the negative staining electron
      microscopy reconstruction of YdiV(4)-FlhD(4)C(2) suggested that the third and
      fourth YdiV molecule bound to the FlhD(4)C(2) complex through squeezing into the
      ring-like structure of FlhD(4)C(2) between the two internal D subunits.
      Consequently, the ring-like structure opened up, and the complex lost DNA-binding
      ability. Thus, YdiV inhibits FlhD(4)C(2) only at relatively high concentrations.

PMID- 23002142
TI  - Baseline brain activity changes in patients with clinically isolated syndrome
      revealed by resting-state functional MRI.
AB  - BACKGROUND: A clinically isolated syndrome (CIS) is the first manifestation of
      multiple sclerosis (MS). Previous task-related functional MRI studies demonstrate
      functional reorganization in patients with CIS. PURPOSE: To assess baseline brain
      activity changes in patients with CIS by using the technique of regional
      amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI.
      MATERIAL AND METHODS: Resting-state fMRIs data acquired from 37 patients with CIS
      and 37 age- and sex-matched normal controls were compared to investigate ALFF
      differences. The relationships between ALFF in regions with significant group
      differences and the EDSS (Expanded Disability Status Scale), disease duration,
      and T2 lesion volume (T2LV) were further explored. RESULTS: Patients with CIS had
      significantly decreased ALFF in the right anterior cingulate cortex, right
      caudate, right lingual gyrus, and right cuneus (P < 0.05 corrected for multiple
      comparisons using Monte Carlo simulation) compared to normal controls, while no
      significantly increased ALFF were observed in CIS. No significant correlation was
      found between the EDSS, disease duration, T2LV, and ALFF in regions with
      significant group differences. CONCLUSION: In patients with CIS, resting-state
      fMRI demonstrates decreased activity in several brain regions. These results are
      in contrast to patients with established MS, in whom ALFF demonstrates several
      regions of increased activity. It is possible that this shift from decreased
      activity in CIS to increased activity in MS could reflect the dynamics of
      cortical reorganization.

PMID- 23002141
TI  - Manipulation of gene expression in zebrafish using caged circular morpholino
      oligomers.
AB  - Morpholino oligomers (MOs) have been widely used to knock down specific genes in
      zebrafish, but their constitutive activities limit their experimental
      applications for studying a gene with multiple functions or within a gene
      network. We report herein a new design and synthesis of caged circular MOs (caged
      cMOs) with two ends linked by a photocleavable moiety. These caged cMOs were
      successfully used to photomodulate beta-catenin-2 and no tail expression in
      zebrafish embryos.

PMID- 23002143
TI  - Measurement of transplanted pancreatic volume using computed tomography:
      reliability by intra- and inter-observer variability.
AB  - BACKGROUND: Unlike other solid organ transplants, pancreas allografts can undergo
      a substantial decrease in baseline volume after transplantation. This phenomenon
      has not been well characterized, as there are insufficient data on reliable and
      reproducible volume assessments. We hypothesized that characterization of
      pancreatic volume by means of computed tomography (CT) could be a useful method
      for clinical follow-up in pancreas transplant patients. PURPOSE: To evaluate the
      feasibility and reliability of pancreatic volume assessment using CT scan in
      transplanted patients. MATERIAL AND METHODS: CT examinations were performed on 21
      consecutive patients undergoing pancreas transplantation. Volume measurements
      were carried out by two observers tracing the pancreatic contours in all slices.
      The observers performed the measurements twice for each patient. Differences in
      volume measurement were used to evaluate intra- and inter-observer variability.
      RESULTS: The intra-observer variability for the pancreatic volume measurements of
      Observers 1 and 2 was found to be in almost perfect agreement, with an intraclass
      correlation coefficient (ICC) of 0.90 (0.77-0.96) and 0.99 (0.98-1.0),
      respectively. Regarding inter-observer validity, the ICCs for the first and
      second measurements were 0.90 (range, 0.77-0.96) and 0.95 (range, 0.85-0.98),
      respectively. CONCLUSION: CT volumetry is a reliable and reproducible method for
      measurement of transplanted pancreatic volume.

PMID- 23002144
TI  - Comparison of the diagnostic value of FDG-PET/CT and axillary ultrasound for the
      detection of lymph node metastases in breast cancer patients.
AB  - BACKGROUND: FDG-PET/CT is increasingly being used for breast cancer staging. Its
      diagnostic accuracy in comparison to ultrasound as the standard non-invasive
      imaging modality for the evaluation of axillary lymph nodes has yet not been
      evaluated. PURPOSE: To retrospectively compare the diagnostic value of full-dose,
      intravenously contrast-enhanced FDG-PET/CT and ultrasound for the detection of
      lymph node metastases in breast cancer patients. MATERIAL AND METHODS: Ninety
      patients (one patient with a bilateral carcinoma) (89 women, one man; mean age,
      55.5 +/- 16.6 years) suffering from primary breast cancer underwent whole-body
      FDG-PET/CT and axillary ultrasound. The ipsilateral axillary fossa (n = 91) was
      evaluated for metastatic spread. The sensitivity, specificity, the positive
      predictive value (PPV), negative predictive value (NPV), and accuracy of both
      methods were calculated. The sensitivity and accuracy were statistically compared
      using the McNemar Test (P <0.05). Analyses were made on a patient basis. The
      number of patients with extra-axillary locoregional lymph node metastases
      exclusively detected by FDG-PET/CT was evaluated. For axillary lymph node
      metastases histopathology served as the reference standard. RESULTS: The
      sensitivity, specificity, PPV, NPV, and accuracy of FDG-PET/CT for the detection
      of axillary lymph node metastases were 54%, 89%, 77%, 74%, and 75%, respectively.
      For ultrasound it was 38%, 78%, 54%, 65%, and 62%, respectively. FDG-PET/CT was
      significantly more accurate than ultrasound for the detection of axillary lymph
      node metastases (P = 0.019). There was no statistically significant difference
      between the sensitivity of both modalities (P = 0.0578). FDG-PET/CT detected
      extra-axillary locoregional lymph node metastases in seven patients (8%) that had
      not been detected by another imaging modality. CONCLUSION: Though more accurate
      compared to ultrasound for evaluating the axillary lymph node status FDG-PET/CT
      is only as sensitive as ultrasound when it comes to the detection of axillary
      lymph node metastases. Due to the low sensitivity FDG-PET/CT cannot act as a
      substitute for Sentinel lymph node biopsy. FDG-PET/CT is able to detect
      previously unknown locoregional extra-axillary lymph node metastases.

PMID- 23002145
TI  - Removal of a frameshift between the hsdM and hsdS genes of the EcoKI Type IA DNA
      restriction and modification system produces a new type of system and links the
      different families of Type I systems.
AB  - The EcoKI DNA methyltransferase is a trimeric protein comprised of two
      modification subunits (M) and one sequence specificity subunit (S). This enzyme
      forms the core of the EcoKI restriction/modification (RM) enzyme. The 3' end of
      the gene encoding the M subunit overlaps by 1 nt the start of the gene for the S
      subunit. Translation from the two different open reading frames is
      translationally coupled. Mutagenesis to remove the frameshift and fuse the two
      subunits together produces a functional RM enzyme in vivo with the same
      properties as the natural EcoKI system. The fusion protein can be purified and
      forms an active restriction enzyme upon addition of restriction subunits and of
      additional M subunit. The Type I RM systems are grouped into families, IA to IE,
      defined by complementation, hybridization and sequence similarity. The fusion
      protein forms an evolutionary intermediate form lying between the Type IA family
      of RM enzymes and the Type IB family of RM enzymes which have the frameshift
      located at a different part of the gene sequence.

PMID- 23002146
TI  - Rbg1-Tma46 dimer structure reveals new functional domains and their role in
      polysome recruitment.
AB  - Developmentally Regulated GTP-binding (DRG) proteins are highly conserved GTPases
      that associate with DRG Family Regulatory Proteins (DFRP). The resulting
      complexes have recently been shown to participate in eukaryotic translation. The
      structure of the Rbg1 GTPase, a yeast DRG protein, in complex with the C-terminal
      region of its DFRP partner, Tma46, was solved by X-ray diffraction. These data
      reveal that DRG proteins are multimodular factors with three additional domains,
      helix-turn-helix (HTH), S5D2L and TGS, packing against the GTPase platform.
      Surprisingly, the S5D2L domain is inserted in the middle of the GTPase sequence.
      In contrast, the region of Tma46 interacting with Rbg1 adopts an extended
      conformation typical of intrinsically unstructured proteins and contacts the
      GTPase and TGS domains. Functional analyses demonstrate that the various domains
      of Rbg1, as well as Tma46, modulate the GTPase activity of Rbg1 and contribute to
      the function of these proteins in vivo. Dissecting the role of the different
      domains revealed that the Rbg1 TGS domain is essential for the recruitment of
      this factor in polysomes, supporting further the implication of these conserved
      factors in translation.

PMID- 23002148
TI  - The Egyptian.

PMID- 23002147
TI  - Genome-wide activation of latent donor splice sites in stress and disease.
AB  - Sequences that conform to the 5' splice site (5'SS) consensus are highly abundant
      in mammalian introns. Most of these sequences are preceded by at least one in
      frame stop codon; thus, their use for splicing would result in pre-maturely
      terminated aberrant mRNAs. In normally grown cells, such intronic 5'SSs appear
      not to be selected for splicing. However, under heat shock conditions aberrant
      splicing involving such latent 5'SSs occurred in a number of specific gene
      transcripts. Using a splicing-sensitive microarray, we show here that stress
      induced (e.g. heat shock) activation of latent splicing is widespread across the
      human transcriptome, thus highlighting the possibility that latent splicing may
      underlie certain diseases. Consistent with this notion, our analyses of data from
      the Gene Expression Omnibus (GEO) revealed widespread activation of latent
      splicing in cells grown under hypoxia and in certain cancers such as breast
      cancer and gliomas. These changes were found in thousands of transcripts
      representing a wide variety of functional groups; among them are genes involved
      in cell proliferation and differentiation. The GEO analysis also revealed a set
      of gene transcripts in oligodendroglioma, in which the level of activation of
      latent splicing increased with the severity of the disease.

PMID- 23002149
TI  - US drug manufacturers set up joint testing group.

PMID- 23002150
TI  - Canadian surgeons are warned of legal suits after bariatric surgery.

PMID- 23002151
TI  - West Nile virus deaths mount in US amid new concerns over renal damage.

PMID- 23002152
TI  - Colonic explosions, chimpanzees' rear ends, and a source of green hair: this
      year's Ig Nobels.

PMID- 23002153
TI  - Retrospective study of patients with acute pancreatitis: is serum amylase still
      required?
AB  - OBJECTIVES: To assess the role of serum amylase and lipase in the diagnosis of
      acute pancreatitis. Secondary aims were to perform a cost analysis of these
      enzyme assays in patients admitted to the surgical admissions unit. DESIGN:
      Cohort study. SETTING: Secondary care. PARTICIPANTS: Patients admitted with
      pancreatitis to the acute surgical admissions unit from January to December 2010
      were included in the study. METHODS: Data collated included demographics,
      laboratory results and aetiology. The cost of measuring a single enzyme assay was
      L0.69 and both assays were L0.99. RESULTS: Of the 151 patients included, 117
      patients had acute pancreatitis with gallstones (n=51) as the most common cause.
      The majority of patients with acute pancreatitis had raised levels of both
      amylase and lipase. Raised lipase levels only were observed in additional 12% and
      23% of patients with gallstone-induced and alcohol-induced pancreatitis,
      respectively. Overall, raised lipase levels were seen in between 95% and 100% of
      patients depending on aetiology. Sensitivity and specificity of lipase in the
      diagnosis of acute pancreatitis was 96.6% and 99.4%, respectively. In contrast,
      the sensitivity and specificity of amylase in diagnosing acute pancreatitis were
      78.6% and 99.1%, respectively. Single lipase assay in all patients presenting
      with abdominal pain to the surgical admission unit would result in a potential
      saving of L893.70/year. CONCLUSIONS: Determining serum lipase level alone is
      sufficient to diagnose acute pancreatitis and substantial savings can be made if
      measured alone.

PMID- 23002154
TI  - Digital acrometastases as first sign of hepatocellular carcinoma.
AB  - Digital acrometastases as a primary presentation of hepatocellular carcinoma
      (HCC) is rare. A 66-year-old man with no history of malignancy presented to the
      plastic surgery department with two skin lesions, one on the bridge of his nose
      and one on distal phalanx of left little finger. A working diagnosis of cutaneous
      metastases was made. Immediately prior to admission for excision of these lesions
      he was admitted with right upper quadrant pain and a jaundiced discolouration of
      the skin. The lesions were excised as planned and histopathological examination
      revealed metastatic HCC. A subsequent magnetic resonance imaging showed a
      lobulated mass consistent with primary HCC.

PMID- 23002155
TI  - Non-stroke admissions to a hyperacute stroke unit.
AB  - A significant proportion of patients presenting to hyperacute stroke units (HSUs)
      are diagnosed with non-stroke (NS). This study aimed to assess the rate and
      diagnoses of NS patients admitted to a HSU and the implications for clinical
      service provision. Admissions to the HSU at the Southern General Hospital,
      Glasgow, were retrospectively assessed (March 2007-September 2007). NS patients
      were identified by two parallel ascertainment methods and NS diagnosis was
      confirmed by case-note and discharge letter review. Of 375 presentations, 116
      (31%) were due to NS. NS diagnosis was more likely for local referrals than from
      regional hospitals (41% versus 19%; P = 0.0002). Compared with stroke/transient
      ischaemic attack patients, NS patients were significantly younger, more likely to
      have an magnetic resonance imaging (MRI) scan and had a shorter length of
      hospital stay. Common NS diagnoses were migraine (22%), functional neurological
      disorder (14%), syncope (12%) and seizure (6%). NS patients who had an MRI scan
      were more likely to have a length of stay >=2 days (75% versus 53%; P = 0.03). NS
      makes up one-third of acute stroke-like presentations with a high frequency of
      neurological conditions. NS patients tend to be younger and require significant
      investigation. The increased use of MRI and neurological services has
      implications for providing a hyperacute stroke service.

PMID- 23002156
TI  - Mesenteric lipoma causing small bowel perforation: a case report and review of
      literature.
AB  - A lipoma of the small bowel mesentery is a rare pathological entity. It has been
      shown to rarely cause obstruction and volvulus of the small bowel. We report a
      case of a 72-year-old man who presented with lower abdominal pain and slightly
      raised inflammatory markers. Computerized tomography of the abdomen showed small
      bowel perforation and oedematous terminal ileum. At laparotomy the cause was
      found to be a mesenteric lipoma causing small bowel perforation. As far as the
      authors are aware, this presentation is not described in the English language
      literature.

PMID- 23002157
TI  - Estimating the potential of tissue donation in Scotland.
AB  - The Scottish National Blood Transfusion Service became the preferred provider of
      tissues in 2000. At that time, the only tissues procured were heart valves and
      some tendons from multiorgan donors. These sources and the range of tissues were
      not enough to provide for the clinical needs of Scottish patients. A systematic
      review was undertaken using the International Classification of Disease codes to
      assess what the potential pool of tissue donors would be by region, hospital and
      hospital department. Such data would enable us to focus our limited resources to
      maximize the yield of tissues to meet clinical demand. The data from this study
      were validated by a case-note audit in one hospital in Edinburgh. It was shown
      that the maximum tissue donor potential of approximately 48.5 per million
      population was in the central belt of Scotland in hospitals with large emergency
      medicine departments.

PMID- 23002158
TI  - Duration of L-dopa and dopamine agonist monotherapy in Parkinson's disease.
AB  - The expected duration of initial antiparkinson monotherapy before the need for
      supplementation is not clearly defined for routine practice. The aim of this
      study was to define the length of L-dopa (L-3, 4-dihydrophenylalanine) and
      dopamine agonist monotherapy. The duration of monotherapy and discontinuation
      rates were investigated in a natural observational setting by plotting Kaplan
      Meier survival curves. Out of 345 patients, 180 (52.2%) received L-dopa and 165
      (47.8%) received a dopamine agonist as initial monotherapy. Half of the patients
      starting L-dopa received supplementary therapy with- in 3.6 years (95% confidence
      interval, 3.2-4.6), significantly longer than for dopamine agonist monotherapy
      (half required a second agent at 2.3 years [2.0-2.9]; P = 0.00017).
      Discontinuation of L-dopa therapy was 1%. Dopamine agonists were stopped (due to
      side-effects like impulse control disorders [6%], somnolence [4%] and light
      headedness [3%]) in 20% over four years. The duration and tolerability of L-dopa
      and dopamine agonists as initial Parkinson's disease monotherapy are defined in
      this study; this may form part of the information exchange with patients.

PMID- 23002159
TI  - Anabolic steroids in patients undergoing total knee arthroplasty.
AB  - OBJECTIVES: To systematically review the evidence for using anabolic-androgenic
      steroids (AAS) to aid rehabilitation following total knee replacement (TKR).
      DESIGN: Systematic review of all clinical study designs. DATA SOURCES: MEDLINE,
      EMBASE, AMED, CINAHL and the Cochrane Library were searched from inception to
      August 2012. ELIGIBILITY CRITERIA: All clinical study designs without language or
      patient demographic limits. OUTCOME MEASURES: All functional, physiological and
      administrative outcomes as well as reporting of adverse events. RESULTS: Only two
      small randomised controlled trials satisfied the inclusion criteria.
      Statistically significant improvements were reported in the AAS group for
      quadriceps strength at 3 (p=0.02), 6 (p=0.01) and 12 (p=0.02) months, Functional
      Independence Measure score at 35 days (p=<0.05) and Knee Society Score at 6 weeks
      (p=0.02), 6 months (p=0.04) and 12 months (p=0.03). However, differences in
      hamstring strength, bone mineral density, sit-to-stand testing, walking speed,
      length of hospital stay and need for further inpatient rehabilitation did not
      reach statistical significance. There were no reported adverse events.
      CONCLUSIONS: There is insufficient evidence to recommend routine administration
      of AAS to patients undergoing TKR. However, pilot data suggest that AAS can be
      administered safely and may improve important postoperative outcome measures.
      This justifies a randomised trial sufficiently powered to identify between-group
      differences likely to be of clinical significance.

PMID- 23002160
TI  - Influence of FCGR3A genotype on the therapeutic response to rituximab in
      rheumatoid arthritis: an observational cohort study.
AB  - OBJECTIVES: To determine whether a polymorphism in the Fcgamma receptor type IIIA
      (FCGR3A-F158V), influencing immunoglobulin G binding affinity, relates to the
      therapeutic efficacy of rituximab in rheumatoid arthritis (RA) patients. DESIGN:
      Observational cohort study. SETTING: Three university hospital rheumatology units
      in Sweden. PARTICIPANTS: Patients with established RA (n=177; 145 females and 32
      males) who started rituximab (Mabthera) as part of routine care. PRIMARY OUTCOME
      MEASURES: Response to rituximab therapy in relation to FCGR3A genotype, including
      stratification for sex. RESULTS: The frequency of responders differed
      significantly across FCGR3A genotypes (p=0.017 in a 3*2 contingency table).
      Heterozygous patients showed the highest response rate at 83%, as compared with
      patients carrying 158FF (68%) or 158VV (56%) (p=0.028 and 0.016, respectively).
      Among 158VV patients, response rates differed between male and female patients
      (p=0.036), but not among 158FF or 158VF patients (p=0.72 and 0.46, respectively).
      CONCLUSIONS: Therapeutic efficacy of rituximab in RA patients is influenced by
      FCGR3A genotype, with the highest response rates found among heterozygous
      patients. This may suggest that different rituximab mechanisms of action in RA
      are optimally balanced in FCGR3A-158VF patients. Similar to the previously
      described associations with RA susceptibility and disease course, the impact of
      158VV on rituximab response may be influenced by sex.

PMID- 23002161
TI  - Preventing renal and cardiovascular risk by renal function assessment: insights
      from a cross-sectional study in low-income countries and the USA.
AB  - OBJECTIVE: To assess the prevalence of microalbuminuria and kidney dysfunction in
      low-income countries and in the USA. DESIGN: Cross-sectional study of screening
      programmes in five countries. SETTING: Screening programmes in Nepal, Bolivia,
      the USA (National Health and Nutrition Examination Survey (NHANES) 2005-2008)
      Bangladesh and Georgia. PARTICIPANTS: General population in Nepal (n=20 811),
      Bolivia (n=3436) and in the USA (n=4299) and high-risk subjects in Bangladesh
      (n=1518) and Georgia (n=1549). PRIMARY AND SECONDARY OUTCOME MEASURES: Estimated
      glomerular filtration rate (eGFR)<60ml/min/1.73 m(2) and microalbuminuria
      (defined as urinary albumin creatinine ratio values of 30-300 mg/g) were the main
      outcome measures. The cardiovascular (CV) risk was also evaluated on the basis of
      demographic, clinical and blood data. RESULTS: The prevalence of
      eGFR<60ml/min/1.73 m(2) was 19%, 3.2% and 7% in Nepal, Bolivia and the USA,
      respectively. In Nepal, 7% of subjects were microalbuminuric compared to 8.6% in
      the USA. The prevalence of participants with predicted 10-year CV disease (CVD)
      risk >=10% was 16.9%, 9.4% and 17% in Nepal, Bolivia and in the USA,
      respectively. In Bangladesh and Georgia, subjects with eGFR<60 ml/min/1.73 m(2)
      were 8.6% and 4.9%, whereas those with microalbuminuria were 45.4% and 56.5%,
      respectively. Predicted 10-year CVD risk >=10% was 25.4% and 25% in Bangladesh
      and Georgia, respectively. CONCLUSIONS: Renal abnormalities are common among low
      income countries and in the USA. Prevention programmes, particularly focused on
      those with renal abnormalities, should be established worldwide to prevent CVD
      and progression to end-stage renal disease.

PMID- 23002162
TI  - Low-copy nuclear primers and ycf1 primers in Cactaceae.
AB  - PREMISE OF THE STUDY: To increase the number of variable regions available for
      phylogenetic study in the Cactaceae, primers were developed for a portion of the
      plastid ycf1 gene and intron-spanning regions of two low-copy nuclear genes
      (isi1, nhx1). * METHODS AND RESULTS: Primers were tested on several families
      within Caryophyllales, focusing on the Cactaceae. Gel electrophoresis indicated
      positive amplification in most samples. Sequences of these three regions (isi1,
      nhx1, ycf1) from Harrisia exhibited variation similar to or greater than two
      plastid regions (atpB-rbcL intergenic spacer and rpl16 intron). * CONCLUSIONS:
      The isi, nhx, and ycf1 primers amplify phylogenetically useful information
      applicable to the Cactaceae and other families in the Caryophyllales.

PMID- 23002164
TI  - Variable length chloroplast markers for population genetic studies in Acmispon
      (Fabaceae).
AB  - PREMISE OF THE STUDY: To estimate genetic structure, chloroplast loci containing
      length-variable regions were developed for two legumes, Acmispon argophyllus and
      A. dendroideus. * METHODS AND RESULTS: Primers for 14 chloroplast loci containing
      repeat regions were developed from the chloroplast genome sequence of the legume
      Lotus japonicus and tested in Acmispon. Nine loci exhibited polymorphism in
      Acmispon, with up to six alleles per locus. Gene diversity ranged from 0 to 0.775
      in A. argophyllus and 0.142 to 0.766 in A. dendroideus. The primers also
      amplified in other Acmispon species. Sequencing of the fragments revealed
      discordance between fragment sizes and underlying sequence for three loci
      containing complex repeat regions. * CONCLUSIONS: Although genotypes were easily
      generated and sized, sequencing may be more informative of genetic variation in
      loci with complex repeat regions. These loci exhibit substantial variation and
      should be useful for understanding genetic structure associated with seed
      dispersal in Acmispon.

PMID- 23002165
TI  - Regulation of plant gravity sensing and signaling by the actin cytoskeleton.
AB  - Gravitropism is a process by which plant organs readjust their growth toward or
      away from the gravity vector when the plant is reoriented. The actin cytoskeleton
      has often been a significant component of models explaining gravitropism, but its
      role in this process has become somewhat controversial in light of reports
      showing that actin inhibitors enhance the gravitropic response. The work with
      inhibitors implies that actin might function as a negative regulator of
      gravitropism. In this article, possibilities for how such a role might be
      accomplished are presented. First, the organization of actin in statocytes is
      revisited in an attempt to rationalize how compressive forces exerted by
      statoliths on membranes can lead to enhanced gravity sensing. Second, recent
      genetic work in the model plant Arabidopsis thaliana is discussed, focusing on
      the potential involvement of the protein degradation machinery in actin-mediated
      control of statolith dynamics and on the intriguing possibility that an actin
      regulated, ligand-receptor mechanism for gravity signal transduction might
      operate in higher plants. Third, modifications in the trafficking of auxin efflux
      transporters are considered as possible mechanisms for the enhanced gravity
      responses observed in plant organs when the actin cytoskeleton is disrupted by
      chemical inhibitors. The various possibilities presented in this review emphasize
      the large amount of research that remains to be done before we can fully
      understand how the actin cytoskeleton modulates tropisms in higher plants.

PMID- 23002166
TI  - Electrocardiographic enigma of a classical disease: pellagra.
AB  - Pellagra is caused by a deficiency of niacin. It is endemic in Africa and Asia
      where the staple diet of the many refugees or displaced people is corn-based and,
      therefore, nicotinic acid-deficient. It is also frequently seen in developed
      countries among chronic alcoholics or, occasionally, those suffering from
      anorexia nervosa. The usual manifestations are diarrhoea, dementia and dermatitis
      (the 3Ds), which if left untreated may lead to death. Cardiac manifestations and
      electrocardiographic changes are rarely seen in those suffering from pellagra. We
      present a case of pellagra in an alcoholic who presented with the classical rash
      over the upper limbs along with electrocardiographic changes but without any
      cardiac symptoms, both of which resolved dramatically after he had been given
      niacin supplements.

PMID- 23002167
TI  - Efficacy of adding clonidine to intrathecal morphine in acute postoperative pain:
      meta-analysis.
AB  - BACKGROUND: Clonidine may be used along with intrathecal morphine for single-dose
      postoperative analgesia in adults. The efficacy of this is not clear. METHODS: A
      meta-analysis was performed for two endpoints of efficacy: the time to first
      postoperative analgesia request and the amount of systemic morphine used during
      the first 24 h after operation. A Bayesian inference supporting direct statements
      about the probability of the magnitude of an effect was also used. The frequency
      of the five adverse events (postoperative nausea or vomiting, sedation,
      respiratory depression, pruritus, and hypotension) was analysed. RESULTS:
      Clonidine increased the duration of analgesia by 1.63 h [95% confidence interval
      (CI): 0.93-2.33]. There is a 90% probability that clonidine increases the
      duration of postoperative analgesia by more than 75 min compared with morphine
      alone. Clonidine reduced the amount of postoperative morphine by a mean of 4.45
      mg (95% CI: 1.40-7.49 mg). There is a probability of 90% to obtain a decrease
      >2.3 mg but only 35% to obtain a decrease >5 mg. The incidence of hypotension was
      the only adverse event increased by clonidine (odds ratio 1.78; 95% CI: 1.02
      3.12). CONCLUSIONS: The addition of clonidine to intrathecal morphine extends the
      time to first analgesia and decreases the amount of morphine used. However, as
      the effects are small, and the results heavily influenced by a study in which
      intrathecal fentanyl was also given, this must be balanced with the increased
      frequency of hypotension.

PMID- 23002170
TI  - The effect of transcatheter arterial chemoembolization on hepatitis C viremia.

PMID- 23002163
TI  - Development and characterization of 59 polymorphic cDNA-SSR markers for the
      edible oil crop Sesamum indicum (Pedaliaceae).
AB  - PREMISE OF THE STUDY: Polymorphic simple sequence repeat markers from transcript
      sequences (cDNA-simple sequence repeat [SSR]) were developed for the edible oil
      crop Sesamum indicum to facilitate the genetic study of this species. * METHODS
      AND RESULTS: We found 7702 SSR loci in the 60960 unigenes, and 1550 primer pairs
      were designed and synthesized. In total, 59 primer pairs showed polymorphism
      within 36 individuals; the number of alleles per locus ranged from two to four,
      and the expected and observed heterozygosity ranged from 0.05 to 0.74 and 0 to
      0.30, respectively. * CONCLUSIONS: These polymorphic markers will greatly
      facilitate studies of the genetic structure of S. indicum populations as well as
      the identification and conservation of the species.

PMID- 23002171
TI  - In reply.

PMID- 23002168
TI  - FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan
      FGFR inhibitor.
AB  - Patient stratification biomarkers that enable the translation of cancer genetic
      knowledge into clinical use are essential for the successful and rapid
      development of emerging targeted anticancer therapeutics. Here, we describe the
      identification of patient stratification biomarkers for NVP-BGJ398, a novel and
      selective fibroblast growth factor receptor (FGFR) inhibitor. By intersecting
      genome-wide gene expression and genomic alteration data with cell line
      sensitivity data across an annotated collection of cancer cell lines called the
      Cancer Cell Line Encyclopedia, we show that genetic alterations for FGFR family
      members predict for sensitivity to NVP-BGJ398. For the first time, we report
      oncogenic FGFR1 amplification in osteosarcoma as a potential patient selection
      biomarker. Furthermore, we show that cancer cell lines harboring FGF19 copy
      number gain at the 11q13 amplicon are sensitive to NVP-BGJ398 only when
      concomitant expression of beta-klotho occurs. Thus, our findings provide the
      rationale for the clinical development of FGFR inhibitors in selected patients
      with cancer harboring tumors with the identified predictors of sensitivity.
      SIGNIFICANCE: The success of a personalized medicine approach using targeted
      therapies ultimately depends on being able to identify the patients who will
      benefit the most from any given drug. To this end, we have integrated the
      molecular profiles for more than 500 cancer cell lines with sensitivity data for
      the novel anticancer drug NVP-BGJ398 and showed that FGFR genetic alterations are
      the most significant predictors for sensitivity. This work has ultimately
      endorsed the incorporation of specific patient selection biomakers in the
      clinical trials for NVP-BGJ398.

PMID- 23002172
TI  - Patients' with obstructive sleep apnoea syndrome (OSAS) preferences and demand
      for treatment: a discrete choice experiment.
AB  - RATIONALE: Despite its high level of effectiveness, initial acceptance of
      continuous positive airway pressure (CPAP) and regular use in patients with
      obstructive sleep apneoa syndrome (OSAS) are still an issue. Alternatively, oral
      appliances (OAs) can be recommended. To improve patient engagement in their
      treatment, physicians are advised to take into account patient preferences and to
      share the therapeutic decision. We aimed to determine patients' preferences for
      OSAS treatment-related attributes, and to predict patients' demand for both CPAP
      and OAs. METHODS: A discrete choice experiment (DCE) was performed in 121 newly
      diagnosed patients consecutively recruited in a sleep unit. RESULTS: Regression
      parameters were the highest for impact on daily life and effectiveness ahead of
      side effects. In the French context, the demanding probabilities for CPAP and OAs
      were 60.2% and 36.2%, respectively. They were sensitive to the variation in the
      amount of out-of-pocket expenses for both CPAP and OAs. CONCLUSIONS: This first
      DCE in OSAS emphasises the importance to communicate with patients before the
      implementation of treatment.

PMID- 23002173
TI  - Respiratory syncytial virus infection of airway epithelial cells, in vivo and in
      vitro, supports pulmonary antibody responses by inducing expression of the B cell
      differentiation factor BAFF.
AB  - BACKGROUND: The mechanisms regulating antibody expression within the human lung
      during airway infection are largely unknown. In this study, our objectives were
      to determine if infection with respiratory syncytial virus (RSV) upregulates
      expression of the B cell differentiation factors A proliferation inducing ligand
      (APRIL) and B cell activating factor of the TNF family (BAFF), if this is a
      common feature of viral airway infection, and how this is regulated in human
      airway epithelial cells. METHODS: We measured BAFF and APRIL protein expression
      in bronchoalveolar lavage (BAL) fluid from infants with severe RSV disease, and
      healthy control children, and in nasopharyngeal aspirates from preschool children
      with other single respiratory viral infections. We also measured mRNA expression
      in bronchial brushings from RSV-infected infants, and in RSV-infected paediatric
      primary airway epithelial cell cultures (pAEC). Beas-2B cell cultures were used
      to examine mechanisms regulating BAFF expression. RESULTS: BAFF protein and mRNA
      were elevated (in marked contrast with APRIL) in BAL and bronchial brushings,
      respectively, from RSV-infected infants. BAFF protein was also found in upper
      airway secretions from children with human metapneumovirus, H1N1, bocavirus,
      rhinovirus, RSV and Mycoplasma pneumoniae infection. BAFF mRNA and protein were
      expressed following in vitro RSV infection of both pAEC and Beas-2B cultures,
      with mRNA expression peaking 12-h postinfection. BAFF induction was blocked by
      addition of a neutralising anti-interferon-beta antibody or palivizumab.
      CONCLUSIONS: BAFF, produced through an interferon-beta-dependent process, is a
      consistent feature of airway infection, and suggests a role for the airway
      epithelia in supporting protective antibody and B cell responses in the lung.

PMID- 23002174
TI  - Intracellular forms of menadione-dependent small-colony variants of methicillin
      resistant Staphylococcus aureus are hypersusceptible to beta-lactams in a THP-1
      cell model due to cooperation between vacuolar acidic pH and oxidant species.
AB  - OBJECTIVES: Phagocytosed methicillin-resistant Staphylococcus aureus (MRSA) are
      susceptible to beta-lactams because of an acid-induced conformational change of
      penicillin-binding protein (PBP) 2a within phagolysosomes. We have examined
      whether this mechanism applies to menD and hemB small-colony variants (SCVs) of
      the COL MRSA strain, using cloxacillin, meropenem, doripenem, and vancomycin as
      comparator. METHODS: Intracellularly, the change in cfu from post-phagocytosis
      inoculum was measured after 24 h of incubation with antibiotics combined or not
      with N-acetylcysteine (NAC; oxidant species scavenger); the relative potency
      (C(s)) was calculated from the Hill equation of concentration-response curves.
      Extracellularly, the effect of a pre-incubation with H(2)O(2) was determined on
      MICs and killing at pH 7.4 and 5.5. RESULTS: Intracellularly, the beta-lactam
      C(s) was similar for the COL strain and the hemB mutant and not modified or
      slightly decreased (2- to 16-fold) by NAC. In contrast, the C(s) was 100- to 900
      fold lower for the menD mutant, but similar to that for the COL strain when NAC
      was present. Extracellularly, beta-lactam MICs were markedly reduced at pH 5.5
      for the parental strain and the haemin-supplemented hemB mutant, with limited
      additional effect of pre-incubation with H(2)O(2). In contrast, MICs remained
      elevated at pH 5.5 for the menD mutant (supplemented with menadione sodium
      bisulphite or not), but were 7-10 dilutions lower after pre-incubation with
      H(2)O(2). Vancomycin MICs were unaltered in all conditions, with no marked effect
      of NAC on C(s). CONCLUSIONS: Cooperation between acidic pH and oxidant species
      confers high potency to beta-lactams against intracellular forms of menD SCVs of
      MRSA.

PMID- 23002175
TI  - Real-time PCR genotyping of Neisseria gonorrhoeae isolates using 14 informative
      single nucleotide polymorphisms on gonococcal housekeeping genes.
AB  - OBJECTIVES: Neisseria gonorrhoeae multilocus sequence typing (MLST) is a key tool
      used to investigate the macroepidemiology of gonococci exhibiting antimicrobial
      resistance (AMR). However, the utility of MLST is undermined by the high workload
      and cost associated with DNA sequencing of seven housekeeping genes. In this
      study, we investigated single nucleotide polymorphism (SNP)-based profiling as a
      means of circumventing these problems. METHODS: A total of 14 SNPs were selected
      following in silico analysis of available N. gonorrhoeae MLST sequence data. Real
      time PCR methods were developed for characterization of each SNP and applied to
      86 N. gonorrhoeae isolates exhibiting a range of ceftriaxone MICs. Twenty-one
      isolates had previously been characterized by MLST. The ability of the real-time
      PCR methods to generate SNP profiles and of the 14 SNP profiles to predict MLST
      types were assessed. RESULTS: In silico analysis of the 217 different MLST types
      available on the Neisseria web site showed 181 different 14 SNP profiles
      (Simpson's index of diversity = 0.998). When the real-time PCR methods were
      applied to the isolates, 29 different 14 SNP profiles were obtained for 83
      isolates. Predicted MLST types were consistent with those for the 21 isolates
      previously characterized by MLST. For 46 isolates with raised ceftriaxone MICs
      (>= 0.03 mg/L), there were 14 different 14 SNP profiles observed, with two
      profiles accounting for more than half of these isolates. CONCLUSIONS: The 14 SNP
      real-time PCR profiling approach is a simple and cost-effective alternative to N.
      gonorrhoeae MLST and could be used to complement current typing schemes in N.
      gonorrhoeae AMR investigations.

PMID- 23002176
TI  - What is a qualitative synthesis?

PMID- 23002178
TI  - Analysis of clothing and urine from Moscow theatre siege casualties reveals
      carfentanil and remifentanil use.
AB  - On October 26, 2002, Russian Special Forces deployed a chemical aerosol against
      Chechen terrorists to rescue hostages in the Dubrovka theatre. Its use confirmed
      Russian military interest in chemicals with effects on personnel and caused 125
      deaths through a combination of the aerosol and inadequate medical care. This
      study provides evidence from liquid chromatography-tandem mass spectrometry
      analysis of extracts of clothing from two British survivors, and urine from a
      third survivor, that the aerosol comprised a mixture of two anaesthetics-
      carfentanil and remifentanil--whose relative proportions this study was unable to
      identify. Carfentanil and remifentanil were found on a shirt sample and a
      metabolite called norcarfentanil was found in a urine sample. This metabolite
      probably originated from carfentanil.

PMID- 23002179
TI  - Brand placement on price boards after tobacco display bans: a point-of-sale audit
      in Melbourne, Australia.
AB  - OBJECTIVE: This study aims to explore how cigarette brands are arranged on boards
      listing tobacco products and/or prices following the 1 January 2011 ban on point
      of-sale tobacco displays in Victoria, Australia. METHODS: An audit undertaken in
      late 2011 gathered information on the prevalence and contents of tobacco product
      information displays ('price boards'). We examined how often all or most of the
      brands listed at the top of price boards were owned by the same tobacco company,
      and whether premium, mainstream and value brands were listed in prominent
      positions more frequently in different store types and socio-economic areas
      (SES). RESULTS: Of the 281 stores audited, 64% (179) had legible price boards. Of
      the 178 with factory-made products, 11% arranged brands alphabetically, 2% by
      price and 87% did so in some other way. In 65% of stores where brands were
      arranged in some other way, at least three of the top four positions were devoted
      to brands owned by the same tobacco company. Premium brands were given greater
      prominence than would be expected by market share. Neighbourhood SES was
      significantly related to the representation in the most prominent price board
      positions of brands from the most appropriate market segment. CONCLUSIONS: Price
      boards are being used to target brands to consumers. Jurisdictions should also
      prohibit price board display when they ban tobacco product display; prices might
      instead be itemised in alphabetical order on a list only viewable upon customer
      request.

PMID- 23002180
TI  - Second-hand smoke exposure and psychological distress in adolescents. A
      population-based study.
AB  - OBJECTIVES: To examine the association between duration and place of second-hand
      smoke (SHS) exposure and psychological distress in adolescents. METHODS: A cross
      sectional study conducted in 2008 and 2009 in a representative sample of 4th-year
      students of secondary education (mean age 15.7 years) in the region of Madrid,
      Spain. The 2215 students who were not smokers were selected for the analysis.
      Duration of SHS exposure within and outside the home was obtained by self-report.
      Psychological distress was defined as a score >= 3 points in the General Health
      Questionnaire (GHQ-12). The analyses were made using logistic regression adjusted
      for demographic variables, lifestyles and family characteristics. RESULTS: Among
      non-smoking adolescents, 27.8% (95% CI 25.5 to 30.0) were exposed to SHS in the
      home, and 33.6% (95% CI 31.3 to 36.0) outside the home. Compared with those with
      no SHS exposure in the home, the multivariate OR for psychological distress was
      1.23 (95% CI 0.92 to 1.64) in individuals with SHS exposure <1 h/day, 2.07 (95%
      CI 1.30 to 3.28) for exposure 1-3 h/day, and 2.24 (95% CI 1.45 to 3.47) for
      exposure >3 h/day (p for linear trend <0.001). No association was observed
      between SHS exposure outside the home and psychological distress. CONCLUSIONS: In
      non-smoking adolescents, duration of exposure to SHS in the home had a positive
      dose-response relationship with the frequency of psychological distress. However
      SHS exposure outside the home did not show an association with mental health.

PMID- 23002181
TI  - Using rate advancement periods for communicating the benefits of quitting smoking
      to older smokers.
AB  - BACKGROUND AND AIMS: Standard epidemiological measures of the risk of premature
      death from smoking might be unsuitable for risk communication in actual
      counselling situations. The rate advancement period (RAP) is an epidemiologic
      metric that could be useful for conveying information on the benefits of
      quitting. More effective risk communication could motivate older smokers to make
      an attempt at quitting. We provide empirical evidence on the impact of smoking,
      and the benefits of quitting on all-cause mortality and RAPs for people aged 60
      years and older in a large cohort of older adults. METHODS: Smoking information
      was obtained from 6545 participants aged 60-74 years of ESTHER, a population
      based German cohort. Cox proportional hazards regression was applied to estimate
      associations of smoking status, amount of smoking and time since smoking
      cessation with all-cause mortality. Premature mortality was quantified by RAPs.
      RESULTS: Current smokers had a 2.5-fold increased risk for all-cause mortality
      (adjusted HR: 2.53, 95% CI 2.10 to 3.03) and an RAP of 10.7 years when compared
      with never smokers. Strong dose-response relationships were seen with both
      current and life-time amount of smoking. Compared with current smokers,
      significant mortality reductions by 30%, 39% and 59%, and rate advancement
      reductions of 4.0, 5.6 and 10.0 years within <10 years, 10-19 years and >=20
      years after cessation were found for former smokers, respectively. CONCLUSIONS:
      Smoking remains a strong risk factor for premature mortality, and smoking
      cessation remains highly beneficial also at older ages.

PMID- 23002182
TI  - Obstetric complications as risk factors for schizophrenia spectrum psychoses in
      offspring of mothers with psychotic disorder.
AB  - BACKGROUND: Obstetric complications have predicted future development of
      schizophrenia in previous studies, but they are also more common in mothers with
      schizophrenia. The aims of this study were to compare the occurrence of obstetric
      complications in children of mothers with schizophrenia spectrum psychoses and
      control children, and to investigate whether obstetric complications predicted
      children's psychiatric morbidity. METHOD: The Helsinki High-Risk (HR) Study
      monitors females born between 1916 and 1948 and treated for schizophrenia
      spectrum disorders in Helsinki psychiatric hospitals, their offspring born
      between 1941 and 1977, and controls. We examined information on obstetric
      complications and neonatal health of 271 HR and 242 control offspring. We
      compared the frequency of obstetric complications and neonatal health problems in
      the HR group vs controls and in HR children who later developed psychotic
      disorders vs healthy HR children. A Cox regression model was used to assess
      whether problems in pregnancy or delivery predicted psychiatric morbidity within
      the HR group. RESULTS: Few differences between HR and control offspring were
      found in obstetric complications. Within the HR group, infections (hazard rate
      ratio [HRR] 3.73, 95% CI 1.27-11.01), hypertension during pregnancy (HRR 4.10,
      95% CI 1.15-14.58), and placental abnormalities (HRR 4.09, 95% CI 1.59-10.49)
      were associated with elevated risk of schizophrenia spectrum psychoses.
      CONCLUSIONS: Common medical problems during pregnancy were associated with
      increased risk of schizophrenia spectrum psychoses in offspring of mothers with
      schizophrenia spectrum psychoses. These results underline the role of the
      prenatal period in the development of schizophrenia and the importance of careful
      monitoring of pregnancies of mothers with psychotic disorder.

PMID- 23002183
TI  - Reduced expression of STOP/MAP6 in mice leads to cognitive deficits.
AB  - BACKGROUND: STOP/MAP6 null (KO) mice recapitulate behavioral abnormalities
      related to positive and negative symptoms and cognitive deficits of
      schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6
      proteins in heterozygous mice (only one allele expressed) would result in
      abnormal behavior related to those displayed by STOP null mice. METHODS: Using a
      comprehensive test battery, we investigated the behavioral phenotype of STOP
      heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals
      raised either in standard conditions (controls) or submitted to maternal
      deprivation. RESULTS: Control Het mice displayed prominent deficits in social
      interaction and learning, resembling KO mice. In contrast, they exhibited short
      lasting locomotor hyperreactivity to acute mild stress and no impaired locomotor
      response to amphetamine, much like WT mice. Additionally, perinatal stress
      deteriorated Het mouse phenotype by exacerbating alterations related to positive
      symptoms such as their locomotor reactivity to acute mild stress and
      psychostimulant challenge. CONCLUSION: Results show that the dosage of
      susceptibility genes modulates their putative phenotypic contribution and that
      STOP expression has a high penetrance on cognitive abilities. Hence, STOP Het
      mice might be useful to investigate cognitive defects related to those observed
      in mental diseases and ultimately might be a valuable experimental model to
      evaluate preventive treatments.

PMID- 23002184
TI  - Lung infiltrates in antiretroviral-naive HIV-infected children with chronic lung
      disease: value of non-bronchoscopic bronchoalveolar lavage in the detection of
      Candida albicans.
AB  - OBJECTIVE: To describe the etiology of lung infiltrates in HIV-infected
      antiretroviral-naive children with chronic persistent/recurrent lung disease in
      whom routine cultures were negative and were non-responders to World Health
      Organization standard antimicrobial therapy. METHOD: Non-bronchoscopic
      bronchoalveolar lavage (NBBAL) was performed on these non-responders. RESULTS:
      Fifty children were enrolled. Single isolates on NBBAL were seen in 28 cases,
      dual pathogens in 5 cases and no growth in 14 cases. Haemophilus influenzae (n =
      12), Candida albicans (n = 5) and Mycobacterium spp. other than tuberculosis (n =
      4) were the commonest pathogens seen. Eight cases with no growth had segmental or
      lobar collapse: in five cases, NBBAL was therapeutic and in two cases, a
      diagnosis of lymphoma was made on open lung biopsy. Thirty-two of the 38 cases
      (84%) had favorable outcomes on follow-up. CONCLUSION: Haemophilus influenzae, C.
      albicans and Mycobacterium spp. other than tuberculosis are important pathogens
      in children with HIV and HIV-associated chronic lung disease.

PMID- 23002185
TI  - Reply to Chen et al.

PMID- 23002186
TI  - Giant aneurysm of the non-coronary sinus of Valsalva.

PMID- 23002187
TI  - Competitive flow arising from varying degrees of coronary artery stenosis affects
      the blood flow and the production of nitric oxide and endothelin in the internal
      mammary artery graft.
AB  - OBJECTIVES: Internal mammary arteries graft failure in coronary artery bypass
      grafting (CABG) is mostly considered to be a result of competitive flow (CF) from
      the native coronary artery, which significantly limits future revascularization
      options. METHODS: With the left internal mammary artery (LIMA) anastomosed to the
      left anterior descending (LAD) coronary artery using an off-pump technique, CABG
      was performed on 15 Chinese swine. Then we produced varying degrees of stenosis
      in the proximal LAD coronary artery with an adjustable flow occluder, measured
      the mean flow of the LIMA and LAD coronary artery and detected the plasma
      concentrations of nitric oxide (NO) and endothelin (ET) in the LIMA graft.
      RESULTS: When stenosis of the proximal LAD artery was decreased, the CF of the
      native LAD coronary artery showed an increasing trend, while the mean flow of the
      LIMA revealed a decreasing trend. Distal LAD coronary artery flow remained nearly
      constant, despite the varying proximal LAD artery or LIMA flow rates. An
      oscillating flow pattern (retrograde/antegrade) was noted in the LIMA graft when
      the proximal LAD coronary artery was not fully occluded. The plasma concentration
      of ET in the LIMA graft was significantly higher than that before grafting (P <
      0.05), and the plasma concentration of NO was significantly lower (P < 0.05). The
      concentration of NO was positively related to the mean flow in the LIMA (r =
      0.872, P < 0.05). CONCLUSIONS: CF from the native LAD coronary artery can
      decrease the blood flow in the LIMA graft and even change the direction of the
      flow. These changes may impair the function of the LIMA graft and affect ET or NO
      production, which in turn may lead to early LIMA graft failure.

PMID- 23002188
TI  - Increased risk of acute kidney injury in patients undergoing tricuspid valve
      surgery.
AB  - OBJECTIVES: We aimed to determine which patients undergoing tricuspid valve (TV)
      surgery are at increased risk for acute kidney injury (AKI). METHODS: We reviewed
      951 patients [mean age 67 +/- 13 years, 573 (60%) female] having TV surgery
      between 2000 and 2007. Analysis focused on clinical outcome; AKI was defined by
      the consensus RIFLE criteria (risk, injury, failure). RESULTS: Surgical
      procedures included isolated TV surgery in 224 (24%) and TV surgery in
      conjunction with another cardiac operation in 727 (76%) patients. TV surgery
      involved redo surgery in 395 (42%). The incidence of postoperative AKI was 30% (n
      = 285), and 75 (7.9%) of these patients required renal replacement therapy. AKI
      stratified by increased RIFLE class was associated with worse postoperative
      outcomes (prolonged intubation, length of hospital stay and mortality; P < 0.001
      for each variable). For patients with AKI, odds ratio for mortality was 4.2 [95%
      confidence interval (CI) 3.2-5.4, P < 0.001; area under receiver operating curves
      0.85 (95% CI 0.80-0.91)], and 2.3 (95% CI 1.9-2.9, P < 0.001) for prolonged
      intubation for each increase in RIFLE class. Independent risk factors for AKI
      were older age, male gender, previous surgery, preoperative anaemia, length of
      cardiopulmonary bypass and TV replacement. Importantly, preoperative creatinine
      and pulmonary artery pressure were not independently associated with AKI.
      CONCLUSIONS: TV surgery carries a high incidence of postoperative AKI that is
      associated with adverse outcome. The use of the RIFLE criteria allows comparison
      with prior studies and is an important predictor of early mortality. The
      estimation of patient risk for AKI should be based on multivariable prediction.

PMID- 23002189
TI  - Vasoregulatory peptides pro-endothelin-1 and pro-adrenomedullin are associated
      with metabolic syndrome in the population-based KORA F4 study.
AB  - BACKGROUND: Metabolic alterations and endothelial dysfunction are interrelated
      processes in type 2 diabetes (T2D) and metabolic syndrome (MetS) that often
      develop in parallel. We assessed the association of vasoactive precursor peptides
      (VPPs) with MetS and T2D. DESIGN AND METHODS: Plasma levels of C-terminal pro
      endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM) were
      measured by novel sensitive assays in 1590 participants of the population-based
      KORA F4 study. The association of the VPPs with T2D, MetS defined by IDF
      criteria, the components of MetS, and insulin resistance (IR) was assessed in
      logistic regression models. RESULTS: Elevated levels of CT-proET-1 and MR-proADM
      were associated with T2D, MetS, and IR in age- and sex-adjusted models. After
      adjustment for age, sex, former vascular complications, lifestyle factors, high
      sensitive C-reactive protein, and serum creatinine, significant associations with
      MetS were found for MR-proADM (OR=5.94, 95% CI 3.78-9.33) and CT-proET-1
      (OR=5.18, 95% CI 3.48-7.71) (top quartile vs bottom quartile). CT-proET-1 and MR
      proADM were strongly associated with all components of MetS as defined by IDF
      criteria. After multivariable adjustment, association of CT-proET-1 and MR-proADM
      with pathological glucose tolerance and T2D disappeared and a borderline
      association with IR was found only for CT-proET-1 (OR=1.34, 95% CI 0.96-1.87).
      CONCLUSIONS: We here demonstrate for the first time that plasma levels of both MR
      proADM and CT-proET-1 levels are related to MetS and its components, thus
      suggesting that they possibly have a role as a surrogate biomarker for the
      disease and its complications.

PMID- 23002190
TI  - A pilot study of the feasibility of a vaginal washing cessation intervention
      among Kenyan female sex workers.
AB  - BACKGROUND: Intravaginal practices including vaginal washing have been associated
      with HIV-1 acquisition. This association may be mediated by mucosal disruption,
      changes in vaginal flora or genital tract inflammatory responses. Reducing
      vaginal washing could lower women's risk of HIV-1 acquisition. METHODS: 23 HIV-1
      seronegative women who reported current vaginal washing were recruited from a
      prospective cohort study of high-risk women in Mombasa, Kenya. A theoretical
      framework including information-motivation-behavioural skills and harm reduction
      was implemented to encourage participants to reduce or eliminate vaginal washing.
      At baseline and after 1 month, we evaluated vaginal epithelial lesions by
      colposcopy, vaginal microbiota by Nugent's criteria and vaginal cytokine milieu
      using ELISA on cervicovaginal lavage specimens. RESULTS: The most commonly
      reported vaginal washing substance was soap with water (N=14, 60.9%). The median
      frequency of vaginal washing was 7 (IQR 7-14) times per week. After 1 month, all
      participants reported cessation of vaginal washing (p=0.01). The probability of
      detecting cervicovaginal epithelial lesions was lower (OR 0.48; 95% CI 0.20 to
      1.16; p=0.10) and the likelihood of detecting Lactobacillus by culture was higher
      (OR 3.71, 95% CI 0.73 to 18.76, p=0.11) compared with baseline, although these
      results were not statistically significant. There was no change in the prevalence
      of bacterial vaginosis. Most cytokine levels were reduced, but these changes were
      not statistically significant. CONCLUSIONS: A theory-based intervention appeared
      to have a positive effect in reducing vaginal washing over 1 month. Larger
      studies with longer follow-up are important to further characterise the effects
      of vaginal washing cessation on biological markers.

PMID- 23002191
TI  - Prevalence of HIV and other sexually transmitted infections and factors
      associated with syphilis among female sex workers in Panama.
AB  - OBJECTIVES: Biological and behavioural surveillance of HIV and sexually
      transmitted infections (STIs) among populations at highest risk have been used to
      monitor trends in prevalence and in risk behaviours. Sex work in Panama is
      regulated through registration with the Social Hygiene Programme, Ministry of
      Health. We estimated prevalence of HIV and STIs, and factors associated with
      active syphilis among female sex workers (FSWs). METHODS: A cross-sectional study
      using venue-based, time-space sampling was conducted among FSWs in Panama from
      2009 to 2010. FSWs were interviewed about sociodemographic characteristics,
      sexual risk behaviour, health history and drug use using an anonymous structured
      questionnaire. Blood was collected for serological testing of HIV and other STIs.
      Factors associated with active syphilis were studied using logistic regression
      analysis. RESULTS: The overall HIV-1 prevalence of 0.7% varied by FSW category;
      1.6% in 379 unregistered, and 0.2% in 620 registered FSWs. Overall prevalence
      (and 95% CI) of STIs were: syphilis antibody, 3.8% (2.7% to 5.2%); herpes simplex
      virus type 2 antibody (anti-HSV-2), 74.2% (71.4% to 76.9%); hepatitis B surface
      antigen, 0.6% (0.2% to 1.3%); hepatitis B core antibody, 8.7% (7.0% to 10.6%);
      and hepatitis C antibody, 0.2% (0.0% to 0.7%). In multivariate analysis,
      registration (adjusted OR (AOR)=0.35; 95% CI 0.16 to 0.74), having a history of
      STI (AOR=2.37; 95% CI 1.01 to 5.58), forced sex (AOR=2.47; 95% CI 1.11 to 5.48),
      and anti-HSV-2 (AOR=10.05; 95% CI 1.36 to 74.38) were associated with active
      syphilis. CONCLUSIONS: Although HIV prevalence is low among FSWs in Panama,
      unregistered FSWs bear a higher burden of HIV and STIs than registered FSWs.
      Programmes aimed at overcoming obstacles to registration, and HIV, STI and harm
      reduction among unregistered FSWs is warranted to prevent HIV transmission, and
      to improve their sexual and reproductive health.

PMID- 23002192
TI  - Condom effectiveness against non-viral sexually transmitted infections: a
      prospective study using electronic daily diaries.
AB  - OBJECTIVES: To prospectively evaluate the protective value of consistent and
      correct use of latex condoms against the acquisition of Chlamydia trachomatis,
      Neisseria gonorrhoeae and Trichomonas vaginalis. METHODS: Patients (N=929)
      attending clinics that treat sexually transmitted infections (STIs) were
      prospectively followed for up to 6 months. Urine STI nucleic acid amplification
      testing was performed at baseline, 3 months and 6 months. Participants were
      instructed to respond to daily prompts from a handheld device by completing a
      report for each penile-vaginal sexual intercourse event. Generalised estimating
      equation models examined associations of consistent as well as consistent and
      correct condom use with STI incidence over 3-month intervals. RESULTS: Consistent
      condom use was not significantly associated with STI incidence (Estimated OR
      (EOR)=0.75; 95% CI (CI) 0.43 to 1.30; p=0.31). However, individuals who used
      condoms both correctly and consistently were estimated to have 59% lower odds of
      acquiring an STI (EOR=0.41; 95% CI  0.19 to 0.90; p=.026), compared to those who
      did not. CONCLUSIONS: The correct as well as the consistent use of condoms
      greatly reduces the odds of non-viral STI acquisition.

PMID- 23002193
TI  - Pregnant women's opinions on the acceptability of providing self-taken vaginal
      swabs for a study of infection and miscarriage.

PMID- 23002194
TI  - Otosyphilis: missed opportunities for early treatment?

PMID- 23002195
TI  - Efficacy and safety of implantable cardiac defibrillators for treatment of
      ventricular arrhythmias in patients with cardiac sarcoidosis.
AB  - AIMS: Implantable cardiac defibrillator (ICD) implantation is a class IIA
      recommendation for patients with cardiac sarcoidosis (CS). However, little is
      known about the efficacy and safety of ICDs in this population. The goal of this
      multicentre retrospective data review was to evaluate the efficacy and safety of
      ICDs in patients with CS. METHODS AND RESULTS: Electrophysiologists at academic
      medical centres were asked to identify consecutive patients with CS and an ICD.
      Clinical information, ICD therapy history, and device complications were
      collected for each patient. Data were collected on 235 patients from 13
      institutions, 64.7% male with mean age 55.6 +/- 11.1. Over a mean follow-up of
      4.2 +/- 4.0 years, 85 of 234 (36.2%) patients received an appropriate ICD therapy
      (shocks and/or anti-tachycardia pacing) and 67 of 226 (29.7%) received an
      appropriate shock. Fifty-seven of 235 patients (24.3%) received a total of 222
      inappropriate shocks. Forty-six adverse events occurred in 41 of 235 patients
      (17.4%). Patients who received appropriate ICD therapies were more likely to be
      male (73.8 vs. 59.6%, P = 0.0330), have a history of syncope (40.5 vs. 22.5%, P =
      0.0044), lower left ventricular ejection fraction (38.1 +/- 15.2 vs. 48.8 +/-
      14.7%, P <= 0.0001), ventricular pacing on baseline electrocardiogram (16.1 vs.
      2.1%, P = 0.0002), and a secondary prevention indication (60.7 vs. 24.5%, P <
      0.0001) compared with those who did not receive appropriate ICD therapies.
      CONCLUSION: Patients with CS and ICDs are at high risk for ventricular
      arrhythmias. This population also has high rates of inappropriate shocks and
      device complications.

PMID- 23002196
TI  - Epicardial catheter ablation for ventricular tachycardia in heparinized patients.
AB  - AIMS: In patients undergoing epicardial catheter ablation of ventricular
      tachycardia (VT), current guidelines recommend obtaining pericardial access prior
      to heparinization to minimize bleeding complications. Consequently, access is
      obtained before endocardial mapping (leading to unnecessary punctures) or during
      an additional procedure. We present our experience of obtaining pericardial
      access during the index procedure in heparinized patients. METHODS AND RESULTS:
      Patients undergoing catheter ablation of VT in whom pericardial access was
      performed after heparinization were included. Clinical and procedural data and
      complications were recorded. Electrocardiograms (ECGs) were analysed for
      published criteria suggesting an epicardial ablation target and compared with
      patients (matched for substrate) undergoing successful endocardial ablation.
      Seventeen patients (13 males, age 58 +/- 16 years, 8 (47%) ischaemic) were
      evaluated. Pericardial access was achieved in 16 (94%), including 2 patients with
      prior epicardial ablation. The mean activated clotting time was 273 +/- 36 s. No
      bleeding complications occurred. In three patients, inadvertent puncture of the
      right ventricle caused no adverse consequences. An epicardial ablation target was
      found in nine of which three (33%) had ECG criteria, suggesting an epicardial
      circuit. In comparison 5 of 17 patients undergoing successful endocardial
      ablation had at least one ECG criterion suggesting an epicardial ablation target.
      CONCLUSION: Obtaining pericardial access for epicardial catheter ablation for VT
      appears to be safe in heparinized patients. Electrocardiogram criteria suggesting
      an epicardial ablation target lack the sensitivity and specificity accurately to
      predict which patients might need epicardial ablation. Performing pericardial
      access in heparinized patients therefore may reduce unnecessary punctures and
      reduce the number of additional procedures in some patients.

PMID- 23002197
TI  - Imaging of an unusual case of a completely unroofed coronary sinus without
      persistent left superior vena cava.

PMID- 23002198
TI  - Isolated papillary muscle hypertrophy: a variant of hypertrophic cardiomyopathy?
      Do not miss a hypertrophic cardiomyopathy.

PMID- 23002199
TI  - Development of the questionnaire on palliative care for advanced dementia (qPAD).
AB  - The Questionnaire on Palliative Care for Advanced Dementia (qPAD) is a 2-part
      instrument that measures long-term care staff knowledge, and beliefs,
      perceptions, and attitudes about palliative and end-of-life care for persons with
      advanced dementia. Factor analyses of the Knowledge Test (coefficient alpha =
      .81) produced 3 factors: Anticipating Needs, Preventing Negative Outcomes, and
      Insight and Intuition (coefficient alpha = .75, .73, and .58, respectively),
      explaining 67% of the total variance. Factor analyses of the Attitude Scale
      (coefficient alpha = .83) produced 3 factors: Job Satisfaction, Perceptions and
      Beliefs, and Work Setting Support of Families (coefficient alpha = .90, .64, and
      .67, respectively), explaining 68% of the total variance. These initial findings
      hold promise for an instrument that measures both knowledge and attitudes of long
      term care staff in the care of persons with advanced dementia.

PMID- 23002200
TI  - Pulmonary vein isolation in a patient with dextrocardia.

PMID- 23002201
TI  - Return to play and future ACL injury risk after ACL reconstruction in soccer
      athletes from the Multicenter Orthopaedic Outcomes Network (MOON) group.
AB  - BACKGROUND: There is limited information on outcomes and return to play (RTP)
      after anterior cruciate ligament reconstruction (ACLR) in soccer athletes.
      PURPOSE: The purpose of this study was to (1) test the hypotheses that player
      sex, side of injury, and graft choice do not influence RTP and (2) define the
      risk for future ACL injury in soccer players after ACLR. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: Soccer players in a prospective cohort were
      contacted to determine RTP after ACLR. Information regarding if and when they
      returned to play, their current playing status, the primary reason they stopped
      playing soccer (if relevant), and incidence of subsequent ACL surgery was
      recorded. RESULTS: Initially, 72% of 100 soccer athletes (55 male, 45 female)
      with a mean age of 24.2 years at the time of ACLR returned to soccer. At average
      follow-up of 7.0 years, 36% were still playing, a significant decrease compared
      with initial RTP (P < .0001). Based on multivariate analysis, older athletes (P =
      .006) and females (P = .037) were less likely to return to play. Twelve soccer
      athletes had undergone further ACL surgery, including 9 on the contralateral knee
      and 3 on the ipsilateral knee. In a univariate analysis, females were more likely
      to have future ACL surgery (20% vs 5.5%, P = .03). Soccer athletes who underwent
      ACLR on their nondominant limb had a higher future rate of contralateral ACLR
      (16%) than soccer athletes who underwent ACLR on their dominant limb (3.5%) (P =
      .03). CONCLUSION: Younger and male soccer players are more likely to return to
      play after ACL reconstruction. Return to soccer after ACLR declines over time.
      ACLR on the nondominant limb potentially places the dominant limb at risk for
      future ACL injury.

PMID- 23002202
TI  - Arthroscopic rotator cuff repair using modified Mason-Allen medial row stitch:
      knotless versus knot-tying suture bridge technique.
AB  - BACKGROUND: When using a method of suture bridge technique, there may be a
      possibility of strangulation of the rotator cuff tendon at the medial row. The
      style of knots chosen to secure the medial row might conceivably be a factor to
      reduce this possibility. PURPOSE: To compare the clinical results and repair
      integrity of arthroscopic rotator cuff repair between a knotless and a
      conventional knot-tying suture bridge technique for patients with full-thickness
      rotator cuff tears and to evaluate retear patterns in the cases with structural
      failure after arthroscopic repair by magnetic resonance imaging (MRI). STUDY
      DESIGN: Cohort study; Level of evidence, 2. METHODS: After arthroscopic repair
      for medium-sized rotator cuff tears, 110 patients available for postoperative MRI
      evaluation at least 6 months were enrolled in this study. According to the repair
      technique, 51 shoulders were enrolled in a knotless suture bridge technique group
      (group A) and 59 shoulders in a conventional knot-tying suture bridge technique
      group (group B). The mean age at the time of the operation was 61.0 years (range,
      44-68 years) in group A and 57.6 years (range, 45-70 years) in group B. The mean
      follow-up period was 21.2 months (range, 12-34 months) and 22.1 months (range, 13
      32 months), respectively. RESULTS: The Constant score of group A increased from
      the preoperative mean of 65.2 points to 79.1 points at the last follow-up (P <
      .001). The corresponding figures for group B improved from 66.6 points to 76.3
      points (P < .001). The preoperative Shoulder Rating Scale of the University of
      California at Los Angeles (UCLA) score was 21.1 points in group A and 18.3 points
      in group B. The UCLA score at the last follow-up was 31.0 points in group A and
      27.9 points in group B (P < .001, P < .001). Retear rate was significantly lower
      in group A (5.9%) than group B (18.6%) (P < .001). In group B, retear occurred at
      the musculotendinous junction in 72.7%, but group A had no medial cuff failure.
      CONCLUSION: In arthroscopic suture bridge repair of full-thickness rotator cuff
      tears, clinical results of both a knotless and a conventional knot-tying group
      showed improvement without significant difference between the 2 groups. However,
      the knotless group had a significantly lower retear rate compared with the
      conventional knot-tying group. A knotless suture bridge technique could be a new
      supplementary repair technique to conventional technique.

PMID- 23002203
TI  - The growing arsenal of ATP-competitive and allosteric inhibitors of BCR-ABL.
AB  - The BCR-ABL fusion kinase is the driving mutation of chronic myelogenous
      leukemias and is also expressed in a subset of acute lymphoblastic leukemias.
      Recent advances in elucidating the structure, regulation, and signaling of BCR
      ABL have led to the identification of allosteric sites that are distant from the
      ATP-binding pocket and are critical for BCR-ABL-dependent oncogenic
      transformation. Here, we review the available data regarding the molecular
      mechanism of action and the specificity of ATP-competitive tyrosine kinase
      inhibitors targeting BCR-ABL. In addition, we discuss how targeting of allosteric
      sites could provide new opportunities to inhibit resistant BCR-ABL mutants,
      either alone or in combination with conventional ATP-competitive inhibitors.

PMID- 23002204
TI  - Cytomegalovirus infection leads to pleomorphic rhabdomyosarcomas in Trp53+/-
      mice.
AB  - Cytomegalovirus (CMV) has been detected in several human cancers, but it has not
      proven to be oncogenic. However, recent studies have suggested mechanisms through
      which cytomegalovirus may modulate the tumor environment, encouraging its study
      as a positive modifier of tumorigenesis. In this study, we investigated the
      effects of cytomegalovirus infection in Trp53 heterozygous mice. Animals were
      infected with murine cytomegalovirus (MCMV) after birth at 2 days (P2) or 4 weeks
      of age and then monitored for tumor formation. Mice injected at 2 days of age
      developed tumors at a high frequency (43%) by 9 months of age. In contrast, only
      3% of mock-infected or mice infected at 4 weeks developed tumors. The majority of
      tumors from P2 MCMV-infected mice were pleomorphic rhabdomyosarcomas (RMS)
      harboring MCMV DNA, RNA, and protein. An examination of clinical cases revealed
      that human RMS (embryonal, alveolar, and pleomorphic) harbored human
      cytomegalovirus IE1 and pp65 protein as well as viral RNA. Taken together, our
      findings offer support for the hypothesis that cytomegalovirus contributes to the
      development of pleomorphic RMS in the context of Trp53 mutation, a situation that
      occurs with high frequency in human RMS.

PMID- 23002205
TI  - Identification of FoxM1/Bub1b signaling pathway as a required component for
      growth and survival of rhabdomyosarcoma.
AB  - We identified Bub1b as an essential element for the growth and survival of
      rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short
      hairpin RNA (shRNA) library screen. Knockdown of Bub1b resulted in suppression of
      tumor growth in vivo, including the regression of established tumors. The
      mechanism by which this occurs is via postmitotic endoreduplication checkpoint
      and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation
      assay, we found that Bub1b is a direct transcriptional target of Forkhead Box M1
      (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A
      resulted in reduction of Bub1b expression and inhibition of cell growth and
      survival. These results show the important role of the Bub1b/FoxM1 pathway in RMS
      and provide potential therapeutic targets.

PMID- 23002206
TI  - Halofuginone inhibits the establishment and progression of melanoma bone
      metastases.
AB  - TGF-beta derived from bone fuels melanoma bone metastases by inducing tumor
      secretion of prometastatic factors that act on bone cells to change the skeletal
      microenvironment. Halofuginone is a plant alkaloid derivative that blocks TGF
      beta signaling with antiangiogenic and antiproliferative properties. Here, we
      show for the first time that halofuginone therapy decreases development and
      progression of bone metastasis caused by melanoma cells through the inhibition of
      TGF-beta signaling. Halofuginone treatment of human melanoma cells inhibited cell
      proliferation, phosphorylation of SMAD proteins in response to TGF-beta, and TGF
      beta-induced SMAD-driven transcription. In addition, halofuginone reduced
      expression of TGF-beta target genes that enhance bone metastases, including
      PTHrP, CTGF, CXCR4, and IL11. Also, cell apoptosis was increased in response to
      halofuginone. In nude mice inoculated with 1205 Lu melanoma cells, a preventive
      protocol with halofuginone inhibited bone metastasis. The beneficial effects of
      halofuginone treatment were comparable with those observed with other anti-TGF
      beta strategies, including systemic administration of SD208, a small-molecule
      inhibitor of TGF-beta receptor I kinase, or forced overexpression of Smad7, a
      negative regulator of TGF-beta signaling. Furthermore, mice with established bone
      metastases treated with halofuginone had significantly less osteolysis than mice
      receiving placebo assessed by radiography. Thus, halofuginone is also effective
      in reducing the progression of melanoma bone metastases. Moreover, halofuginone
      treatment reduced melanoma metastasis to the brain, showing the potential of this
      novel treatment against cancer metastasis.

PMID- 23002207
TI  - Induction of the stem-like cell regulator CD44 by Rho kinase inhibition
      contributes to the maintenance of colon cancer-initiating cells.
AB  - The difficulty in expanding cancer-initiating cells in vitro is one of major
      obstacles for their biochemical characterization. We found that Rho kinase (ROCK)
      inhibitors as well as blebbistatin, a myosin II inhibitor, greatly facilitated
      the establishment of spheroids from primary colon cancer. The spheroid cells
      expressed cancer stem cell markers, showed the ability to differentiate, and
      induced tumors in mice. The spheroids were composed of cells that express various
      levels of CD44, whereas CD44(high) cells were associated with increased sphere
      forming ability, expression of the activating form of beta-catenin, and elevated
      levels of glycolytic genes, CD44(-/low) cells showed increased levels of
      differentiation markers and apoptotic cells. The spheroid cells expressed variant
      forms of CD44 including v6, and the induction of the variants was associated with
      the activating phosphorylation of c-Met. As expected from the predicted
      hierarchy, CD44(high) cells differentiated into CD44(-/low) cells. Unexpectedly,
      a fraction of CD44(-/low) cells generated CD44(high) cells, and the ROCK
      inhibitor or blebbistatin primed the transition by inducing CD44 expression. We
      propose that the transition from CD44(-/low) to CD44(high) state helps to
      maintain a CD44(high) fraction and the tumorigenic diversity in colon cancer.

PMID- 23002208
TI  - Chemotherapeutic sensitivity of testicular germ cell tumors under hypoxic
      conditions is negatively regulated by SENP1-controlled sumoylation of OCT4.
AB  - Testicular germ cell tumors (TGCT) generally respond well to chemotherapy, but
      tumors that express low levels of the transcription factor OCT4 are associated
      with chemoresistance and poor prognosis. Hypoxia is known to induce drug
      resistance in TGCTs; however, the mechanistic basis for reduced expression of
      OCT4 and drug resistance is unclear. Here we show that hypoxia reduces OCT4
      levels and increases the resistance of embryonal carcinoma (EC) cells to
      cisplatin and bleomycin. Furthermore, we show that the loss of OCT4 expression
      under hypoxia can be triggered by sumoylation, which was regulated by SUMO1 and
      the SUMO1 peptidase SENP1. Under hypoxic conditions, overexpression of SUMO1gg
      (the active form of SUMO1) not only increased the level of sumoylated OCT4 (Su
      OCT4), but also decreased the stability of OCT4 protein. In addition,
      overexpression of SENP1 reduced the Su-OCT4 level induced by SUMO1gg
      overexpression, thereby maintaining OCT4 levels and enhancing chemosensitivity.
      Mechanistic investigations revealed that OCT4 sumoylation occurred at K123, as
      overexpression of an OCT4-K123R mutant effectively reduced the level of Su-OCT4
      under hypoxic conditions. Taken together, our results showed that hypoxia reduces
      OCT4 expression levels in ECs to increase drug resistance and that these effects
      could be countered to ablate the suppressive effects of hypoxia on
      chemosensitivity. Our findings also highlight SENP1 as a potential therapeutic
      target for drug resistant TGCTs.

PMID- 23002209
TI  - Microenvironmental regulation of epithelial-mesenchymal transitions in cancer.
AB  - The evolution of the cancer cell into a metastatic entity is the major cause of
      death in patients with cancer. Activation of the epithelial-to-mesenchymal
      transition (EMT) endows invasive and metastatic properties upon cancer cells that
      favor successful colonization of distal target organs. The observation that in
      many cancers distant metastases resemble the epithelial phenotype of primary
      tumors has led to speculation that the disseminated tumor cells recruited to the
      target organs undergo mesenchymal-to-epithelial transition (MET). However, the
      MET cascade has not been recapitulated in vivo, and the cellular and molecular
      regulators that promote MET remain unknown. In a recent report, using a model of
      spontaneous breast cancer, we have shown that bone marrow-derived myeloid
      progenitor cells in the premetastatic lung secrete the proteoglycan versican,
      which induces MET of metastatic tumor cells and accelerates metastases. This
      review summarizes recent progress in MET research, outlines a unique paracrine
      cross-talk between the microenvironment and the cancer cells, which promotes
      tumor outgrowth in the metastatic organ, and discusses opportunities for novel
      antimetastatic approaches for cancer therapy.

PMID- 23002210
TI  - Intratumor heterogeneity: evolution through space and time.
AB  - Recent technologic advances have permitted higher resolution and more rapid
      analysis of individual cancer genomes at the single-nucleotide level. Such
      advances have shown bewildering intertumor heterogeneity with limited somatic
      alterations shared between tumors of the same histopathologic subtype.
      Exacerbating such complexity, increasing evidence of intratumor genetic
      heterogeneity (ITH) is emerging, both within individual tumor biopsies and
      spatially separated between biopsies of the same tumor. Sequential analysis of
      tumors has also revealed evidence that ITH temporally evolves during the disease
      course. ITH has implications for predictive or prognostic biomarker strategies,
      where the tumor subclone that may ultimately influence therapeutic outcome may
      evade detection because of its absence or presence at low frequency at diagnosis
      or because of its regional separation from the tumor biopsy site. In this review,
      the implications of "trunk and branch" tumor evolution for drug discovery
      approaches and emerging evidence that low-frequency somatic events may drive
      tumor growth through paracrine signaling fostering a tumor ecologic niche are
      discussed. The concept of an "actionable mutation" is considered within a model
      of clonal dominance and heterogeneous tumor cell dependencies. Evidence that
      cancer therapeutics may augment ITH and the need to track the tumor subclonal
      architecture through treatment are defined as key research areas. Finally, if
      combination therapeutic approaches to limit the consequences of ITH prove
      challenging, identification of drivers or suppressors of ITH may provide
      attractive therapeutic targets to limit tumor evolutionary rates and adaptation.

PMID- 23002211
TI  - Adenylate kinase-4 is a marker of poor clinical outcomes that promotes metastasis
      of lung cancer by downregulating the transcription factor ATF3.
AB  - Biomarkers predicting metastatic capacity might assist the development of better
      therapeutic strategies for aggressive cancers such as lung cancer. In this study,
      we show that adenylate kinase-4 (AK4) is a progression-associated gene in human
      lung cancer that promotes metastasis. Analysis of published microarray data
      showed that AK4 was upregulated in lung adenocarcinoma compared with normal
      cells. High AK4 expression was associated with advanced stage, disease recurrence
      and poor prognosis. Loss of AK4 expression suppressed the invasive potential of
      lung cancer cell lines, whereas AK4 overexpression promoted invasion in vitro and
      in vivo. Mechanistically, the transcription factor ATF3 was identified as a
      pivotal regulatory target of AK4. Simultaneous reduction in AK4 and ATF3
      expression abolished the inhibitory effects of ATF3 on invasion. ATF3
      overexpression in AK4-overexpressing cells limits invasion activity. Furthermore,
      patients with high AK4 and low ATF3 expression showed unfavorable outcomes
      compared with patients with low AK4 and high ATF3 expression. Taken together, our
      findings indicated that AK4 promotes malignant progression and recurrence by
      promoting metastasis in an ATF3-dependent manner.

PMID- 23002213
TI  - Association of left ventricular diastolic function with systolic dyssynchrony: a
      population study.
AB  - AIMS: Left ventricular (LV) (dys)synchrony has an important impact on LV function
      and structure. Our study aimed to describe the distribution and determinants of
      LV mechanical delay indexes in the general population and to assess an
      association of different Doppler indexes reflecting LV diastolic function with LV
      mechanical delay indexes. METHODS AND RESULTS: In 200 subjects enrolled in a
      family-based population study (46.5% women; mean age, 57.9; 48% hypertensive), we
      performed echocardiography with tissue synchronization imaging (TSI) and two
      dimensional speckle tracking. We measured the maximum difference in time to peak
      systolic velocity between any 2 of 12 LV segments (Ts-max); the standard
      deviation of time to peak systolic velocity of 12 segments (Ts-sd); the
      difference in time to peak systolic velocity and strain between septal and
      lateral LV walls and the strain delay index in septal and lateral walls [septal
      and lateral (SDI)]. In univariable and multivariable regression analyses, TSI
      indexes and lateral SDI independently increased with age (P <= 0.027) and body
      mass index (P <= 0.010). Ts-max and Ts-sd also increased with female sex (P <=
      0.0002) and decreased with heart rate (P <= 0.0004). Septal SDI only increased
      with female sex (P < 0.0001). Among the Doppler indexes of LV diastolic function,
      only E/e' was significantly and positively associated with TSI indexes (P <=
      0.037) and lateral SDI (P = 0.0026), but not with septal SDI (P = 0.69). In
      participants with advanced stage of LV diastolic dysfunction, TSI indexes were
      prolonged compare with subjects with normal LV diastolic function (P <= 0.002).
      CONCLUSION: We demonstrated that in unselected subjects LV diastolic dysfunction
      was associated with mechanical LV dyssynchrony as assessed by echocardiography.

PMID- 23002214
TI  - Age, gender, blood pressure, and ventricular geometry influence normal 3D blood
      flow characteristics in the left heart.
AB  - AIMS: The aim of this study was to assess the effect of age, gender,
      physiological, and global cardiac function parameters on differences in normal 3D
      blood flow in the left ventricle (LV) and atrium (LA) using 4D flow magnetic
      resonance imaging (MRI). METHODS AND RESULTS: Four-dimensional flow MRI was
      acquired in healthy volunteers of two age and gender groups: <30 years (6 women,
      n = 12) and >50 years (6 women, n = 12). Systolic and early to mid-diastolic
      vortex flow (number of vortices, duration, area, peak velocity inside the vortex)
      in the LA and LV was assessed using intra-cardiac flow visualization based on 3D
      particle traces and velocity vector fields. A larger number of vortices in the LA
      were found in young compared with older individuals (number of diastolic
      vortices: 1.6 +/- 0.8 vs. 0.7 +/- 0.7, P = 0.01) with higher velocities (54 +/-
      12 cm/s vs. 41 +/- 11 cm/s in systole, 47 +/- 13 vs. 31 +/- 8 cm/s in diastole, P
      < 0.05). Vortices in the LV base were smaller in women compared with men (369 +/-
      133 vs. 543 +/- 176 mm(2), P = 0.009), while vortex size was increased in mid
      ventricular locations (maximum area: 546 +/- 321 vs. 293 +/- 174 mm(2), P <
      0.05). Correlation analysis revealed significant relationships (P = 0.005-0.048,
      correlation coefficients = 0.44-0.84) between LA and LV vortex characteristics
      (number, size, vortex velocities) and blood pressure as well as end-diastolic
      volume, LV length, and ejection fraction. CONCLUSIONS: Flow patterns in the left
      heart demonstrated differences related to age, gender, blood pressure, and
      ventricular geometry. The findings constitute a prerequisite for the
      understanding of the impact of cardiac disease on intra-cardiac haemodynamics.

PMID- 23002215
TI  - Non-invasive detection of tako-tsubo cardiomyopathy vs. acute anterior myocardial
      infarction by transthoracic Doppler echocardiography.
AB  - AIMS: Typical tako-tsubo cardiomyopathy (TTC) mimics acute anterior myocardial
      infarction (AMI) and the differential diagnosis is challenging before coronary
      angiography (CA) is performed; it demonstrates reduced or absent antegrade flow
      in the left anterior descending artery (LAD) in AMI, whereas there is no such
      flow limiting in TTC. At the acute phase, we tested the usefulness of the distal
      LAD flow visualization by transthoracic Doppler echocardiography (TDE) to
      distinguish between these two diseases. For this purpose, we prospectively
      enrolled 28 consecutive patients with TTC (75 +/- 10 years, 93% females) who were
      compared with 28 consecutive patients with AMI treated successfully by primary
      angioplasty (66 +/- 12 years, 79% females). All the patients underwent the
      assessment of the distal LAD flow just before CA, using colour and pulsed-wave
      TDE. In addition, the symmetric involvement of wall motion abnormalities (WMAs)
      based on the extent of the disease far beyond one coronary territory in TTC was
      searched by TDE. Non-invasive coronary flow reserve (CFR) by TDE, in the distal
      LAD, was also performed within 1 day after admission. RESULTS: Before CA, the
      distal LAD flow was visible in 38 of 56 cases (68%) in the whole population, in
      all cases with TTC and in 10 cases with AMI (36%). The sensitivity (Se) and
      specificity (Sp) of the LAD flow visualization for the diagnosis of TTC were 100
      and 64%, respectively, with a diagnostic accuracy of 82%. In comparison, the
      pattern of WMA yielded a Se of 75% and Sp of 86%, and a diagnostic accuracy of
      80%. With the combination of both tools, the Se and Sp to detect TTC were 75 and
      96% respectively, with a diagnostic accuracy of 86%. After CA, the acute CFR was
      less severely impaired in the TTC group when compared with the AMI group (2.2 +/-
      0.5 vs. 1.7 +/- 0.6, P < 0.01) despite a worse LV systolic dysfunction.
      CONCLUSION: Non-invasive evaluation of the distal LAD flow could be helpful to
      differentiate TTC from AMI, and its combination with the pattern of WMA improved
      slightly its diagnostic accuracy. Furthermore, the acute CFR is less severely
      impaired in TTC compared with AMI despite poorer LV systolic dysfunction,
      suggesting that other mechanisms than direct microcirculatory damage are also
      involved in the pathogenesis of WMAs in TTC.

PMID- 23002216
TI  - Dynamic localization of Tat protein transport machinery components in
      Streptomyces coelicolor.
AB  - The Tat pathway transports folded proteins across the bacterial cytoplasmic
      membrane and is a major route of protein export in the Streptomyces genus of
      bacteria. In this study, we have examined the localization of Tat components in
      the model organism Streptomyces coelicolor by constructing enhanced green
      fluorescent protein (eGFP) and mCherry fusions with the TatA, TatB, and TatC
      proteins. All three components colocalized dynamically in the vegetative hyphae,
      with foci of each tagged protein being prominent at the tips of emerging germ
      tubes and of the vegetative hyphae, suggesting that this may be a primary site of
      Tat secretion. Time-lapse imaging revealed that localization of the Tat
      components was highly dynamic during tip growth and again demonstrated a strong
      preference for apical sites in growing hyphae. During aerial hypha formation,
      TatA-eGFP and TatB-eGFP fusions relocalized to prespore compartments, indicating
      repositioning of Tat components during the Streptomyces life cycle.

PMID- 23002217
TI  - Inactivation of ribosomal protein genes in Bacillus subtilis reveals importance
      of each ribosomal protein for cell proliferation and cell differentiation.
AB  - Among the 57 genes that encode ribosomal proteins in the genome of Bacillus
      subtilis, a Gram-positive bacterium, 50 genes were targeted by systematic
      inactivation. Individual deletion mutants of 16 ribosomal proteins (L1, L9, L15,
      L22, L23, L28, L29, L32, L33.1, L33.2, L34, L35, L36, S6, S20, and S21) were
      obtained successfully. In conjunction with previous reports, 22 ribosomal
      proteins have been shown to be nonessential in B. subtilis, at least for cell
      proliferation. Although several mutants that harbored a deletion of a ribosomal
      protein gene did not show any significant differences in any of the phenotypes
      that were tested, various mutants showed a reduced growth rate and reduced levels
      of 70S ribosomes compared with the wild type. In addition, severe defects in the
      sporulation frequency of the DeltarplA (L1) mutant and the motility of the
      DeltarpsU (S21) mutant were observed. These data provide the first evidence in B.
      subtilis that L1 and S21 are required for the progression of cellular
      differentiation.

PMID- 23002218
TI  - Two protein lysine methyltransferases methylate outer membrane protein B from
      Rickettsia.
AB  - Rickettsia prowazekii, the etiologic agent of epidemic typhus, is a potential
      biological threat agent. Its outer membrane protein B (OmpB) is an immunodominant
      antigen and plays roles as protective envelope and as adhesins. The observation
      of the correlation between methylation of lysine residues in rickettsial OmpB and
      bacterial virulence has suggested the importance of an enzymatic system for the
      methylation of OmpB. However, no rickettsial lysine methyltransferase has been
      characterized. Bioinformatic analysis of genomic DNA sequences of Rickettsia
      identified putative lysine methyltransferases. The genes of the potential
      methyltransferases were synthesized, cloned, and expressed in Escherichia coli,
      and expressed proteins were purified by nickel-nitrilotriacetic acid (Ni-NTA)
      affinity chromatography. The methyltransferase activities of the purified
      proteins were analyzed by methyl incorporation of radioactively labeled S
      adenosylmethionine into recombinant fragments of OmpB. Two putative recombinant
      methyltransferases (rRP789 and rRP027-028) methylated recombinant OmpB fragments.
      The specific activity of rRP789 is 10- to 30-fold higher than that of rRP027-028.
      Western blot analysis using specific antibodies against trimethyl lysine showed
      that both rRP789 and rRP027-028 catalyzed trimethylation of recombinant OmpB
      fragments. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis
      showed that rRP789 catalyzed mono-, di-, and trimethylation of lysine, while
      rRP027-028 catalyzed exclusively trimethylation. To our knowledge, rRP789 and
      rRP027-028 are the first biochemically characterized lysine methyltransferases of
      outer membrane proteins from Gram-negative bacteria. The production and
      characterization of rickettsial lysine methyltransferases provide new tools to
      investigate the mechanism of methylation of OmpB, effects of methylation on the
      structure and function of OmpB, and development of methylated OmpB-based
      diagnostic assays and vaccine candidates.

PMID- 23002219
TI  - Mycobacterium tuberculosis CwsA interacts with CrgA and Wag31, and the CrgA-CwsA
      complex is involved in peptidoglycan synthesis and cell shape determination.
AB  - Bacterial cell division and cell wall synthesis are highly coordinated processes
      involving multiple proteins. Here, we show that Rv0008c, a novel small membrane
      protein from Mycobacterium tuberculosis, localizes to the poles and on membranes
      and shows an overall punctate localization throughout the cell. Furthermore,
      Rv0008c interacts with two proteins, CrgA and Wag31, implicated in peptidoglycan
      (PG) synthesis in mycobacteria. Deletion of the Rv0008c homolog in M. smegmatis,
      MSMEG_0023, caused bulged cell poles, formation of rounded cells, and defects in
      polar localization of Wag31 and cell wall synthesis, with cell wall synthesis
      measured by the incorporation of the [(14)C]N-acetylglucosamine cell wall
      precursor. The M. smegmatis MSMEG_0023 crgA double mutant strain showed severe
      defects in growth, viability, cell wall synthesis, cell shape, and the
      localization of the FtsZ, FtsI, and Wag31 proteins. The double mutant strain also
      exhibited increased autolytic activity in the presence of detergents. Because
      CrgA and Wag31 proteins interact with FtsI individually, we believe that
      regulated cell wall synthesis and cell shape maintenance require the concerted
      actions of the CrgA, Rv0008c, FtsI, and Wag31 proteins. We propose that,
      together, CrgA and Rv0008c, renamed CwsA for cell wall synthesis and cell shape
      protein A, play crucial roles in septal and polar PG synthesis and help
      coordinate these processes with the FtsZ-ring assembly in mycobacteria.

PMID- 23002220
TI  - Iron-regulated surface determinant (Isd) proteins of Staphylococcus lugdunensis.
AB  - Staphylococcus lugdunensis is the only coagulase-negative Staphylococcus species
      with a locus encoding iron-regulated surface determinant (Isd) proteins. In
      Staphylococcus aureus, the Isd proteins capture heme from hemoglobin and transfer
      it across the wall to a membrane-bound transporter, which delivers it into the
      cytoplasm, where heme oxygenases release iron. The Isd proteins of S. lugdunensis
      are expressed under iron-restricted conditions. We propose that S. lugdunensis
      IsdB and IsdC proteins perform the same functions as those of S. aureus. S.
      lugdunensis IsdB is the only hemoglobin receptor within the isd locus. It
      specifically binds human hemoglobin with a dissociation constant (K(d)) of 23 nM
      and transfers heme on IsdC. IsdB expression promotes bacterial growth in an iron
      limited medium containing human hemoglobin but not mouse hemoglobin. This
      correlates with weak binding of IsdB to mouse hemoglobin in vitro. Unlike IsdB
      and IsdC, the proteins IsdJ and IsdK are not sorted to the cell wall in S.
      lugdunensis. In contrast, IsdJ expressed in S. aureus and Lactococcus lactis is
      anchored to peptidoglycan, suggesting that S. lugdunensis sortases may differ in
      signal recognition or could be defective. IsdJ and IsdK are present in the
      culture supernatant, suggesting that they could acquire heme from the external
      milieu. The IsdA protein of S. aureus protects bacteria from bactericidal lipids
      due to its hydrophilic C-terminal domain. IsdJ has a similar region and protected
      S. aureus and L. lactis as efficiently as IsdA but, possibly due to its location,
      was less effective in its natural host.

PMID- 23002221
TI  - Fur activates expression of the 2-oxoglutarate oxidoreductase genes (oorDABC) in
      Helicobacter pylori.
AB  - Helicobacter pylori is a highly successful pathogen that colonizes the gastric
      mucosa of ~50% of the world's population. Within this colonization niche, the
      bacteria encounter large fluctuations in nutrient availability. As such, it is
      critical that this organism regulate expression of key metabolic enzymes so that
      they are present when environmental conditions are optimal for growth. One such
      enzyme is the 2-oxoglutarate (alpha-ketoglutarate) oxidoreductase (OOR), which
      catalyzes the conversion of alpha-ketoglutarate to succinyl coenzyme A (succinyl
      CoA) and CO(2). Previous studies from our group suggested that the genes that
      encode the OOR are activated by iron-bound Fur (Fe-Fur); microarray analysis
      showed that expression of oorD, oorA, and oorC was altered in a fur mutant strain
      of H. pylori. The goal of the present work was to more thoroughly characterize
      expression of the oorDABC genes in H. pylori as well as to define the role of Fe
      Fur in this process. Here we show that these four genes are cotranscribed as an
      operon and that expression of the operon is decreased in a fur mutant strain.
      Transcriptional start site mapping and promoter analysis revealed the presence of
      a canonical extended -10 element but a poorly conserved -35 element upstream of
      the +1. Additionally, we identified a conserved Fur binding sequence ~130 bp
      upstream of the transcriptional start site. Transcriptional analysis using
      promoter fusions revealed that this binding sequence was required for Fe-Fur
      mediated activation. Finally, fluorescence anisotropy assays indicate that Fe-Fur
      specifically bound this Fur box with a relatively high affinity (dissociation
      constant [K(d)] = 200 nM). These findings provide novel insight into the genetic
      regulation of a key metabolic enzyme and add to our understanding of the diverse
      roles Fur plays in gene regulation in H. pylori.

PMID- 23002222
TI  - Identification of proteins likely to be involved in morphogenesis, cell division,
      and signal transduction in Planctomycetes by comparative genomics.
AB  - Members of the Planctomycetes clade share many unusual features for bacteria.
      Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and
      FtsZ, they divide by polar budding, and they are capable of endocytosis.
      Planctomycete genomes have remained enigmatic, generally being quite large (up to
      9 Mb), and on average, 55% of their predicted proteins are of unknown function.
      Importantly, proteins related to the unusual traits of Planctomycetes remain
      largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in
      an effort to predict proteins that are likely to be involved in
      compartmentalization, cell division, and signal transduction. We used three
      complementary strategies. First, we defined the Planctomycetes core genome and
      subtracted genes of well-studied model organisms. Second, we analyzed the gene
      content and synteny of morphogenesis and cell division genes and combined both
      methods using a "guilt-by-association" approach. Third, we identified signal
      transduction systems as well as sigma factors. These analyses provide a
      manageable list of candidate genes for future genetic studies and provide
      evidence for complex signaling in the Planctomycetes akin to that observed for
      bacteria with complex life-styles, such as Myxococcus xanthus.

PMID- 23002223
TI  - Construction and characterization of a derivative of Neisseria gonorrhoeae strain
      MS11 devoid of all opa genes.
AB  - To better understand the role of Opa in gonococcal infections, we created and
      characterized a derivative of MS11 (MS11Deltaopa) that had the coding sequence
      for all 11 Opa proteins deleted. The MS11Deltaopa bacterium lost the ability to
      bind to purified lipooligosaccharide (LOS). While nonpiliated MS11Deltaopa and
      nonpiliated Opa-expressing MS11 cells grew at the same rate, nonpiliated
      MS11Deltaopa cells rarely formed clumps of more than four bacteria when grown in
      broth with vigorous shaking. Using flow cytometry analysis, we demonstrated that
      MS11Deltaopa produced a homogeneous population of bacteria that failed to bind
      monoclonal antibody (MAb) 4B12, a MAb specific for Opa. Opa-expressing MS11 cells
      consisted of two predominant populations, where ~85% bound MAb 4B12 to a
      significant level and the other population bound little if any MAb. Approximately
      90% of bacteria isolated from a phenotypically Opa-negative colony (a colony that
      does not refract light) failed to bind MAb 4B12; the remaining 10% bound MAb to
      various degrees. Piliated MS11Deltaopa cells formed dispersed microcolonies on
      ME180 cells which were visually distinct from those of piliated Opa-expressing
      MS11 cells. When Opa expression was reintroduced into MS11Deltaopa, the adherence
      ability of the strain recovered to wild-type levels. These data indicate that Opa
      contributes to both bacterium-bacterium and bacterium-host cell interactions.

PMID- 23002224
TI  - A MarR-Type regulator directly activates transcription from the Brucella abortus
      virB promoter by sharing a redundant role with HutC.
AB  - Type IV secretion systems (T4SS) are multiprotein structures that direct the
      translocation of specific molecules across the bacterial cell envelope. As in
      other bacteria, pathogenicity of the genus Brucella essentially depends on the
      integrity of the T4SS-encoding virB operon, whose expression is regulated by
      multiple transcription factors belonging to different families. Previously, we
      identified IHF and HutC, two direct regulators of the virB genes that were
      isolated from total protein extracts of Brucella. Here, we report the
      identification of MdrA, a third regulatory element that was isolated using the
      same screening procedure. This transcription factor, which belongs to the MarR
      family of transcriptional regulators, binds at two different sites of the virB
      promoter and regulates expression in a growth phase-dependent manner. Like other
      members of the MarR family, specific ligands were able to dissociate MdrA from
      DNA in vitro. Determination of the MdrA-binding sites by DNase I footprinting and
      analyses of protein-DNA complexes by electrophoresis mobility shift assays
      (EMSAs) showed that MdrA competes with IHF and HutC for the binding to the
      promoter because their target DNA sequences overlap. Unlike IHF, both MdrA and
      HutC bound to the promoter without inducing bending of DNA. Moreover, the two
      latter transcription factors activated virB expression to similar extents, and in
      doing so, they are functionally redundant. Taken together, our results show that
      MdrA is a regulatory element that directly modulates the activity of the virB
      promoter and is probably involved in coordinating gene expression in response to
      specific environmental signals.

PMID- 23002225
TI  - The structure of the PapD-PapGII pilin complex reveals an open and flexible P5
      pocket.
AB  - P pili are hairlike polymeric structures that mediate binding of uropathogenic
      Escherichia coli to the surface of the kidney via the PapG adhesin at their tips.
      PapG is composed of two domains: a lectin domain at the tip of the pilus followed
      by a pilin domain that comprises the initial polymerizing subunit of the 1,000
      plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin
      domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in
      which a beta strand of PapD temporarily completes the pilin domain's fold,
      preventing premature, nonproductive interactions with other pilin subunits and
      facilitating subunit folding. Chaperone-subunit complexes are delivered to the
      outer membrane usher where donor strand exchange (DSE) replaces PapD's donated
      beta strand with an amino-terminal extension on the next incoming pilin subunit.
      This occurs via a zip-in-zip-out mechanism that initiates at a relatively
      accessible hydrophobic space termed the P5 pocket on the terminally incorporated
      pilus subunit. Here, we solve the structure of PapD in complex with the pilin
      domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an
      immunoglobulin fold with a missing seventh strand, complemented in parallel by
      the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone
      pilin complexes indicated that the interactive surfaces are highly conserved.
      Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as
      molecular dynamics simulations revealed, switches between an open and a closed
      conformation due to the flexibility of the surrounding loops. Our study reveals
      the structural details of the DSE mechanism.

PMID- 23002226
TI  - Wall teichoic acids restrict access of bacteriophage endolysin Ply118, Ply511,
      and PlyP40 cell wall binding domains to the Listeria monocytogenes peptidoglycan.
AB  - The C-terminal cell wall binding domains (CBDs) of phage endolysins direct the
      enzymes to their binding ligands on the bacterial cell wall with high affinity
      and specificity. The Listeria monocytogenes Ply118, Ply511, and PlyP40 endolysins
      feature related CBDs which recognize the directly cross-linked peptidoglycan
      backbone structure of Listeria. However, decoration with fluorescently labeled
      CBDs primarily occurs at the poles and septal regions of the rod-shaped cells. To
      elucidate the potential role of secondary cell wall-associated carbohydrates such
      as the abundant wall teichoic acid (WTA) on this phenomenon, we investigated CBD
      binding using L. monocytogenes serovar 1/2 and 4 cells deficient in WTA. Mutants
      were obtained by deletion of two redundant tagO homologues, whose products
      catalyze synthesis of the WTA linkage unit. While inactivation of either tagO1
      (EGDe lmo0959) or tagO2 (EGDe lmo2519) alone did not affect WTA content, removal
      of both alleles following conditional complementation yielded WTA-deficient
      Listeria cells. Substitution of tagO from an isopropyl-beta-d
      thiogalactopyranoside-inducible single-copy integration vector restored the
      original phenotype. Although WTA-deficient cells are viable, they featured severe
      growth inhibition and an unusual coccoid morphology. In contrast to CBDs from
      other Listeria phage endolysins which directly utilize WTA as binding ligand, the
      data presented here show that WTAs are not required for attachment of CBD118,
      CBD511, and CBDP40. Instead, lack of the cell wall polymers enables unrestricted
      spatial access of CBDs to the cell wall surface, indicating that the abundant WTA
      can negatively regulate sidewall localization of the cell wall binding domains.

PMID- 23002227
TI  - Genetic and biochemical characterizations of enzymes involved in Streptococcus
      pneumoniae serotype 2 capsule synthesis demonstrate that Cps2T (WchF) catalyzes
      the committed step by addition of beta1-4 rhamnose, the second sugar residue in
      the repeat unit.
AB  - Five genes (cps2E, cps2T, cps2F, cps2G, and cps2I) are predicted to encode the
      glycosyltransferases responsible for synthesis of the Streptococcus pneumoniae
      serotype 2 capsule repeat unit, which is polymerized to yield a branched surface
      structure containing glucose-glucuronic acid linked to a glucose-rhamnose
      rhamnose-rhamnose backbone. Cps2E is the initiating glycosyltransferase, but
      experimental evidence supporting the functions of the remaining
      glycosyltransferases is lacking. To biochemically characterize the
      glycosyltransferases, the donor substrate dTDP-rhamnose was first synthesized
      using recombinant S. pneumoniae enzymes Cps2L, Cps2M, Cps2N, and Cps2O. In in
      vitro assays with each of the glycosyltransferases, only reaction mixtures
      containing recombinant Cps2T, dTDP-rhamnose, and the Cps2E product (undecaprenyl
      pyrophosphate glucose) generated a new product, which was consistent with lipid
      linked glucose-rhamnose. cps2T, cps2F, and cps2I deletion mutants produced no
      detectable capsule, but trace amounts of capsule were detectable in Deltacps2G
      mutants, suggesting that Cps2G adds a nonbackbone sugar. All Deltacps2F,
      Deltacps2G, and Deltacps2I mutants contained different secondary suppressor
      mutations in cps2E, indicating that the initial mutations were lethal in the
      absence of reduced repeat unit synthesis. Deltacps2T mutants did not contain
      secondary mutations affecting capsule synthesis. The requirement for secondary
      mutations in mutants lacking Cps2F, Cps2G, and Cps2I indicates that these
      activities occur downstream of the committed step in capsule synthesis and reveal
      that Cps2T catalyzes this step. Therefore, Cps2T is the beta1-4
      rhamnosyltransferase that adds the second sugar to the repeat unit and, as the
      committed step in type 2 repeat unit synthesis, is predicted to be an important
      point of capsule regulation.

PMID- 23002229
TI  - Cold shock genes cspA and cspB from Caulobacter crescentus are
      posttranscriptionally regulated and important for cold adaptation.
AB  - Cold shock proteins (CSPs) are nucleic acid binding chaperones, first described
      as being induced to solve the problem of mRNA stabilization after temperature
      downshift. Caulobacter crescentus has four CSPs: CspA and CspB, which are cold
      induced, and CspC and CspD, which are induced only in stationary phase. In this
      work we have determined that the synthesis of both CspA and CspB reaches the
      maximum levels early in the acclimation phase. The deletion of cspA causes a
      decrease in growth at low temperature, whereas the strain with a deletion of cspB
      has a very subtle and transient cold-related growth phenotype. The cspA cspB
      double mutant has a slightly more severe phenotype than that of the cspA mutant,
      suggesting that although CspA may be more important to cold adaptation than CspB,
      both proteins have a role in this process. Gene expression analyses were carried
      out using cspA and cspB regulatory fusions to the lacZ reporter gene and showed
      that both genes are regulated at the transcriptional and posttranscriptional
      levels. Deletion mapping of the long 5'-untranslated region (5'-UTR) of each gene
      identified a common region important for cold induction, probably via translation
      enhancement. In contrast to what was reported for other bacteria, these cold
      shock genes have no regulatory regions downstream from ATG that are important for
      cold induction. This work shows that the importance of CspA and CspB to C.
      crescentus cold adaptation, mechanisms of regulation, and pattern of expression
      during the acclimation phase apparently differs in many aspects from what has
      been described so far for other bacteria.

PMID- 23002228
TI  - Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin
      resistant, rpoB mutant Mycobacterium tuberculosis.
AB  - Multidrug-resistant tuberculosis has emerged as a major threat to tuberculosis
      control. Phylogenetically related rifampin-resistant actinomycetes with mutations
      mapping to clinically dominant Mycobacterium tuberculosis mutations in the rpoB
      gene show upregulation of gene networks encoding secondary metabolites. We
      compared the expressed proteomes and metabolomes of two fully drug-susceptible
      clinical strains of M. tuberculosis (wild type) to those of their respective
      rifampin-resistant, rpoB mutant progeny strains with confirmed rifampin
      monoresistance following antitubercular therapy. Each of these strains was also
      used to infect gamma interferon- and lipopolysaccharide-activated murine J774A.1
      macrophages to analyze transcriptional responses in a physiologically relevant
      model. Both rpoB mutants showed significant upregulation of the polyketide
      synthase genes ppsA-ppsE and drrA, which constitute an operon encoding
      multifunctional enzymes involved in the biosynthesis of phthiocerol
      dimycocerosate and other lipids in M. tuberculosis, but also of various secondary
      metabolites in related organisms, including antibiotics, such as erythromycin and
      rifamycins. ppsA (Rv2931), ppsB (Rv2932), and ppsC (Rv2933) were also found to be
      upregulated more than 10-fold in the Beijing rpoB mutant strain relative to its
      wild-type parent strain during infection of activated murine macrophages. In
      addition, metabolomics identified precursors of phthiocerol dimycocerosate, but
      not the intact molecule itself, in greater abundance in both rpoB mutant
      isolates. These data suggest that rpoB mutation in M. tuberculosis may trigger
      compensatory transcriptional changes in secondary metabolism genes analogous to
      those observed in related actinobacteria. These findings may assist in developing
      novel methods to diagnose and treat drug-resistant M. tuberculosis infections.

PMID- 23002230
TI  - Estimation of completeness of case ascertainment of Austrian cancer incidence
      data using the flow method.
AB  - BACKGROUND: The international comparability of data from population-based cancer
      registries depends strongly on the completeness of case ascertainment.
      Furthermore, Austrian observed incidence rates suggest that the completeness of
      case ascertainment differs between Austrian federal states. Completeness of case
      ascertainment is to be investigated on national and regional level. METHODS: We
      used the flow method to evaluate the completeness of the Austrian National Cancer
      Registry. This method is based on the logical flow of data in the registration
      system, and on the time distribution of various probabilities inherent in this
      flow. RESULTS: Overall completeness of the Austrian cancer incidence data 2005
      was 94.2% after a registration period of 5 years. The flow method found striking
      differences in completeness between the federal states, which are contrary to the
      time series analyses. CONCLUSION: Overall completeness of the Austrian National
      Cancer Registry is in concordance with estimates from international registries.
      The biggest part of the decrease of incidence rates in the past 2 published years
      seems to be a result of incompleteness. The importance of the registration date
      of a cancer case and the survival time on completeness estimation using the flow
      method has become apparent. Further investigation into the comparability of
      registration date between the federal states and into the quality of survival
      time estimates is recommended.

PMID- 23002231
TI  - Trends in self-reported BMI and prevalence of obesity 2002-10 in Stockholm
      County, Sweden.
AB  - BACKGROUND: Trends in obesity have been reported to level off in several Western
      countries. The aim of this study was to investigate trends in body mass index
      (BMI) and prevalence of obesity between 2002 and 2010 in Stockholm County,
      Sweden. METHODS: Three cross-sectional questionnaires from the Stockholm Health
      Surveys were used for this study. A total of 31 182, 34 707 and 30 767 men and
      women aged between 18 and 64 years completed the questionnaire regarding
      sociodemographic factors, health parameters, physical activity, smoking habits
      and anthropometry in 2002, 2006 and 2010, respectively (response rate: 62.5, 61.3
      and 55.6%, respectively). Linear regression was used to investigate changes in
      mean BMI. Relative risk regression models were used to investigate changes in
      prevalence of obesity, defined as BMI >= 30 kg/m(2). All analyses were stratified
      on age and further adjusted for smoking, education and socioeconomic position.
      RESULTS: Between 2002 and 2006, a stabilization was found in BMI and prevalence
      of obesity in both men and women. But from 2006 to 2010, BMI and prevalence of
      obesity had increased, also among the young. In 2010, the prevalence of obesity
      was 12.2% among men and 10.3% among women. CONCLUSION: After a period of
      stabilization in 2002-06, BMI and prevalence of obesity are increasing in
      Stockholm County, Sweden.

PMID- 23002232
TI  - Psychosocial health and gambling problems among men and women aged 16-24 years in
      the Swedish National Public Health Survey.
AB  - BACKGROUND: This study aimed to explore the association between psychosocial
      health, gambling and gambling problems in a nationally representative sample of
      Swedish youth aged 16-24 years. Another aim was to examine whether these
      associations were different between young men and women. METHODS: Data were from
      the cross-sectional Swedish National Public Health Survey in 2004-07. With a
      response rate of 60.1%, the sample consisted of 19 016 youth. Using a sex
      stratified multinomial logistic regression, we estimated associations between
      psychosocial health variables and gambling and gambling problems. RESULTS: Among
      males, we found that the higher the alcohol consumption, the higher the
      likelihood of gambling and gambling problems. Men with high alcohol consumption
      had an almost four times higher likelihood of gambling problems than men with no
      or low alcohol consumption (OR 3.94, 95% CI: 2.17-7.14). Moreover, young male
      victims of violence were more than twice as likely to have gambling problems than
      non-victims (OR 2.35, 95% CI: 1.39-3.99). Among young women, we found an inverse
      association between high alcohol consumption and gambling problems (OR 0.15, 95%
      CI: 0.05-0.44), opposite that of the young men. Furthermore, psychological
      distress (OR 6.15, 95% CI: 2.15-17.60) and suicidality (OR 2.88, 95% CI: 1.16
      7.17) were associated with higher probabilities of gambling problems among young
      women. CONCLUSION: Alcohol use, violence victimization and poor mental health are
      associated with gambling problems among Swedish youth, however, with important
      sex differences. Prevention of youth gambling should consider sex differences and
      psychosocial health in addition to gambling.

PMID- 23002233
TI  - Dual use of cigarettes and Swedish snuff (snus) among young adults in Northern
      Finland.
AB  - BACKGROUND: The sale of smokeless tobacco has been totally banned in Finland
      since the country joined the European Union in 1995. Adolescents have continued
      to use smokeless tobacco even after the sales ban. The objective was to describe
      dual use of Swedish snuff (snus) and cigarettes in young adults living in
      Northern Finland. METHODS: This study on male military recruits (n = 1151, mean
      age 19.4 years; response rate 80%) investigated association of snus use with self
      reported tobacco use, nicotine dependence and attempts to quit smoking. RESULTS:
      Overall, 15.6% (n = 179) reported daily snus use, and almost half of them were
      dual users who used both products, i.e. cigarettes and snus, daily. Daily smokers
      were often occasional snus users (66.3%), and those with dual use smoked equal
      number of cigarettes per day as daily smokers who were not snus users. In
      addition, dual snus use seemed to increase the dependence to cigarettes, although
      this trend did not reach statistical significance. Dual users tried to quit less
      likely than exclusive smokers. Very few snus users were 'switchers' (ex-smokers)
      [3.2% (n = 22) of all snus users]. CONCLUSIONS: Dual use of snus and cigarettes
      is common among young in Finland, despite the sales ban on snus. The role of snus
      in reducing cigarette smoking is unclear, but it is likely that snus use
      complicates the attempts to quit smoking.

PMID- 23002234
TI  - A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid
      biosynthetic pathway by isoxyl and thiacetazone.
AB  - Isoxyl (ISO) and thiacetazone (TAC), two prodrugs once used in the clinical
      treatment of tuberculosis, have long been thought to abolish Mycobacterium
      tuberculosis (M. tuberculosis) growth through the inhibition of mycolic acid
      biosynthesis, but their respective targets in this pathway have remained elusive.
      Here we show that treating M. tuberculosis with ISO or TAC results in both cases
      in the accumulation of 3-hydroxy C(18), C(20), and C(22) fatty acids, suggestive
      of an inhibition of the dehydratase step of the fatty-acid synthase type II
      elongation cycle. Consistently, overexpression of the essential hadABC genes
      encoding the (3R)-hydroxyacyl-acyl carrier protein dehydratases resulted in more
      than a 16- and 80-fold increase in the resistance of M. tuberculosis to ISO and
      TAC, respectively. A missense mutation in the hadA gene of spontaneous ISO- and
      TAC-resistant mutants was sufficient to confer upon M. tuberculosis high level
      resistance to both drugs. Other mutations found in hypersusceptible or resistant
      M. tuberculosis and Mycobacterium kansasii isolates mapped to hadC. Mutations
      affecting the non-essential mycolic acid methyltransferases MmaA4 and MmaA2 were
      also found in M. tuberculosis spontaneous ISO- and TAC-resistant mutants. That
      MmaA4, at least, participates in the activation of the two prodrugs as proposed
      earlier is not supported by our biochemical evidence. Instead and in light of the
      known interactions of both MmaA4 and MmaA2 with HadAB and HadBC, we propose that
      mutations affecting these enzymes may impact the binding of ISO and TAC to the
      dehydratases.

PMID- 23002235
TI  - Flow-sensitive K+-coupled ATP secretion modulates activity of the epithelial Na+
      channel in the distal nephron.
AB  - The epithelial Na(+) channel (ENaC) in the aldosterone-sensitive distal nephron
      (ASDN) is under tonic inhibition by a local purinergic signaling system
      responding to changes in dietary sodium intake. Normal BK(Ca) channel function is
      required for flow-sensitive ATP secretion in the ASDN. We tested here whether ATP
      secreted through connexin channels in a coupled manner with K(+) efflux through
      BK(Ca) channels is required for inhibitory purinergic regulation of ENaC in
      response to increases in sodium intake. Inhibition of connexin channels relieves
      purinergic inhibition of ENaC. Deletion of the BK-beta4 regulatory subunit, which
      is required for normal BK(Ca) channel function and flow-sensitive ATP secretion
      in the ASDN, suppresses increases in urinary ATP in response to increases in
      sodium intake. As a consequence, ENaC activity, particularly in the presence of
      high sodium intake, is inappropriately elevated in BK-beta4 null mice. ENaC in BK
      beta4 null mice, however, responds normally to exogenous ATP, indicating that
      increases in activity do not result from end-organ resistance but rather from
      lowered urinary ATP. Consistent with this, disruption of purinergic regulation
      increases ENaC activity in wild type but not BK-beta4 null mice. Consequently,
      sodium excretion is impaired in BK-beta4 null mice. These results demonstrate
      that the ATP secreted in the ASDN in a BK(Ca) channel-dependent manner is
      physiologically available for purinergic inhibition of ENaC in response to
      changes in sodium homeostasis. Impaired sodium excretion resulting form loss of
      normal purinergic regulation of ENaC in BK-beta4 null mice likely contributes to
      their elevated blood pressure.

PMID- 23002236
TI  - Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic
      activation of lysosomal proteases.
AB  - Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor
      progression. Emerging evidence suggests that pharmacological modulation of
      autophagy is a promising therapeutic strategy for cancer. However, few autophagy
      modulating compounds are currently approved for clinical use in humans. Matrine
      is a natural compound extracted from traditional Chinese medicine that is widely
      used for treatment of a variety of diseases without any obvious side effects.
      Recently, matrine has been reported to induce autophagy and autophagic cell death
      in cancer cells, although the underlying mechanisms have yet to be elucidated.
      Here, we systematically examined the autophagic events induced by matrine in
      SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells
      was verified by the conversion of microtubule-associated protein light chain 3 as
      well as confocal and transmission electron microscopy. Furthermore, we
      demonstrated that matrine blocked autophagic degradation by impairing the
      activities of lysosomal proteases. Moreover, confocal microscopy and gradient
      ultracentrifugation revealed that the trafficking processes and proteolytic
      activation of cathepsins were inhibited by matrine. Using a pH sensor probe, we
      found elevated pH values in endosomes/lysosomes in response to matrine treatment.
      Therefore, matrine seems to be a novel autophagy inhibitor that can modulate the
      maturation process of lysosomal proteases.

PMID- 23002238
TI  - HIV testing and counselling for migrant populations living in high-income
      countries: a systematic review.
AB  - BACKGROUND: The barriers to HIV testing and counselling that migrants encounter
      can jeopardize proactive HIV testing that relies on the fact that HIV testing
      must be linked to care. We analyse available evidence on HIV testing and
      counselling strategies targeting migrants and ethnic minorities in high-income
      countries. METHODS: Systematic literature review of the five main databases of
      articles in English from Europe, North America and Australia between 2005 and
      2009. RESULTS: Of 1034 abstracts, 37 articles were selected. Migrants, mainly
      from HIV-endemic countries, are at risk of HIV infection and its consequences.
      The HIV prevalence among migrants is higher than the general population's, and
      migrants have higher frequency of delayed HIV diagnosis. For migrants from
      countries with low HIV prevalence and for ethnic minorities, socio-economic
      vulnerability puts them at risk of acquiring HIV. Migrants have specific legal
      and administrative impediments to accessing HIV testing-in some countries,
      undocumented migrants are not entitled to health care-as well as cultural and
      linguistic barriers, racism and xenophobia. Migrants and ethnic minorities fear
      stigma from their communities, yet community acceptance is key for well-being.
      CONCLUSIONS: Migrants and ethnic minorities should be offered HIV testing, but
      the barriers highlighted in this review may deter programs from achieving the
      final goal, which is linking migrants and ethnic minorities to HIV clinical care
      under the public health perspective.

PMID- 23002239
TI  - Selection and mortality: a ten-year follow-up of income decile mortality in
      Norway.
AB  - BACKGROUND: There is universal agreement that higher mortality goes with lower
      income. Opinions differ on causality: the association may reflect the damaging
      effect of poverty on health and survival chances. Conversely, it may reflect
      selection/reverse causation: low income indicates health problems, and from
      health problems follow a higher risk of dying. METHODS: We studied all deaths in
      Norway (111,504) during the 10-year period 1994-2003 among persons aged 25-66
      years in 1993 (2,261,076). For each year, age-standardized mortality rates were
      calculated for each 1993 income decile for men and women separately. Income was
      calculated as family size-adjusted income after taxes but including cash welfare
      transfers. If the selection theory was correct, one would expect to see the
      excess mortality in the lower income fractiles decline as the bad risks, over
      represented among the poorer, died away. RESULTS: Large income decile variations
      in mortality remained at the end of the 10-year period: after 10 years, the age
      standardized mortality rate for men and women was still much higher in the lower
      income deciles. CONCLUSION: As the excess mortality in the poorer income deciles
      was not much reduced during the 10-year period, excess mortality among persons in
      bad health in the lower income deciles does not explain the income inequality in
      mortality in our data set.

PMID- 23002237
TI  - IkappaBKbeta and NFkappaB1, NSAID use and risk of colorectal cancer in the Colon
      Cancer Family Registry.
AB  - The NFkappaB-signaling pathway regulates cell proliferation and inflammation.
      Activation of the pathway is implicated in the etiology of colorectal cancer
      (CRC). NSAIDs may reduce CRC risk partially through a nuclear factor-kappa B
      (NFkappaB)-dependent pathway. In this study, we investigated associations between
      34 NFkappaB1 and 8 IkappaBKbeta tagSNPs and CRC risk and examined interactions
      with non-steroidal anti-inflammatory drug (NSAID) use. Using conditional logistic
      regression, we investigated these associations among 1584 incident CRC cases and
      2516 sibling controls from the Colon Cancer Family Registry. Three IkappaBKbeta
      SNPs were associated with a statistically significant lower colorectal or colon
      cancer risk: rs9694958 (A>G intron 5) (colorectal: OR(hzv) = 0.26(0.07-0.99),
      P(trend) = 0.048, P(adj) = 0.25), rs10958713 (A>C intron 19) (colon: OR(hzv) =
      0.62(0.42-0.92), P(trend) = 0.005, P(adj) = 0.03) and rs5029748 (C>A intron 2)
      (colon: OR(het) = 0.72(0.56-0.91), P(trend) = 0.01, P(adj) = 0.08). We replicated
      trends associated with NFkappaB1 and IkappaBKbeta variants identified in a
      previous study (rs4648110 (T>A intron 22), rs13117745 (G>A intron 5) and
      rs3747811 (T>A intron 1)). IkappaBKbeta's rs6474387 (C>T intron 20) and
      rs11986055 (A>C intron 2) showed substantially lower colon cancer risk among
      current NSAID users (P(interaction) = 0.01 and P(interaction) = 0.045,
      respectively), whereas NFkappaB1's rs230490 (G>A 5' (outside UTR)) and rs997476
      (C>A 3' (outside UTR)) showed higher CRC risk among current NSAID users
      (P(interaction) = 0.01 and P(interaction) = 0.03, respectively). These findings
      suggest that variants in NFkappaB1 and IkappaBKbeta are associated with CRC risk
      and NSAIDs may function partially through an NFkappaB-dependent pathway. The SNPs
      identified here should be considered for future functional studies and may be
      useful in designing a pharmacogenetic approach to preventive NSAID use.

PMID- 23002240
TI  - The mismatch between high effort and low reward in household and family work
      predicts impaired health among mothers.
AB  - BACKGROUND: So far, Siegrist's model of effort-reward imbalance (ERI) has been
      tested almost exclusively for paid employment. This article reports results on a
      newly developed questionnaire measuring ERI in unpaid household and family work.
      METHODS: Using data of a population-based sample of 3129 German mothers, logistic
      regression analyses were performed to test the following three main assumptions:
      (i) high effort combined with low reward in household and family work increases
      the risk of poor health; (ii) a high level of overcommitment may enhance the risk
      of poor health; and (iii) mothers reporting an extrinsic high ERI and a high
      level of overcommitment have an even higher risk of poor health. RESULTS: ERI was
      significantly related to self-rated health, somatic complaints and mental health.
      A high level of overcommitment increased the risk of poor health, whereas ERI and
      overcommitment combined was associated with the highest risk of poor health.
      Statistically significant synergy effects of combined exposure of ERI and
      overcommitment were found for 'anxiety'. CONCLUSIONS: With some limitations, all
      three assumptions underlying the ERI model were confirmed. Thus, we conclude that
      ERI is applicable to domestic work and may provide an explanatory framework to
      assess stress experiences in mothers.

PMID- 23002241
TI  - Psychosocial work factors and sickness absence in 31 countries in Europe.
AB  - BACKGROUND: The studies on the associations between psychosocial work factors and
      sickness absence have rarely included a large number of factors and European
      data. The objective was to examine the associations between a large set of
      psychosocial work factors following well-known and emergent concepts and sickness
      absence in Europe. METHODS: The study population consisted of 14,881 male and
      14,799 female workers in 31 countries from the 2005 European Working Conditions
      Survey. Psychosocial work factors included the following: decision latitude,
      psychological demands, social support, physical violence, sexual harassment,
      discrimination, bullying, long working hours, shift and night work, job
      insecurity, job promotion and work-life imbalance. Covariates were as follows:
      age, occupation, economic activity, employee/self-employed status and physical,
      chemical, biological and biomechanical exposures. Statistical analysis was
      performed using multilevel negative binomial hurdle models to study the
      occurrence and duration of sickness absence. RESULTS: In the models, including
      all psychosocial work factors together and adjustment for covariates, high
      psychological demands, discrimination, bullying, low-job promotion and work-life
      imbalance for both genders and physical violence for women were observed as risk
      factors of the occurrence of sickness absence. Bullying and shift work increased
      the duration of absence among women. Bullying had the strongest association with
      sickness absence. CONCLUSION: Various psychosocial work factors were found to be
      associated with sickness absence. A less conservative analysis exploring each
      factor separately provided a still higher number of risk factors. Preventive
      measures should take psychosocial work environment more comprehensively into
      account to reduce sickness absence and improve health at work at European level.

PMID- 23002242
TI  - FOXO1 impairs whereas statin protects endothelial function in diabetes through
      reciprocal regulation of Kruppel-like factor 2.
AB  - AIMS: Kruppel-like factor 2 (KLF2) is implicated as a key molecule maintaining
      endothelial function. This study was designed to evaluate the reciprocal
      regulation of KLF2 by the forkhead transcription factor FOXO1, and the 3-hydroxy
      3-methylglutaryl coenzyme A reductase inhibitor atorvastatin, in hyperglycaemic
      conditions. METHODS AND RESULTS: Exposure of human umbilical vein endothelial
      cells to 30 mM glucose activated FOXO1 and suppressed KLF2. These effects were
      reversed by FOXO1 small interfering RNA. Adenoviral transfection of
      constitutively active FOXO1 suppressed KLF2 expression. Interestingly,
      atorvastatin inhibited FOXO1 by increasing phosphorylation and also by inhibiting
      nuclear localization and replenished KLF2 in high-glucose conditions. This effect
      of atorvastatin was attenuated by mevalonate. Chromatin immunoprecipitation
      analysis demonstrated that glucose increased whereas atorvastatin decreased FOXO1
      binding to the promoter region of the KLF2 gene. In the vessels of Otsuka Long
      Evans Tokushima Fatty rats, animal models of type 2 diabetes, FOXO1 was activated
      and KLF2 was suppressed, and this was reversed by atorvastatin treatment. The
      arteries from Otsuka Long-Evans Tokushima Fatty rats showed impairment of
      endothelium-dependent vasodilatation, and both atorvastatin and KLF2 gene
      therapies restored it. CONCLUSIONS: Suppression of KLF2 by FOXO1 may be a
      plausible mechanism of diabetic endothelial dysfunction. High-glucose-induced,
      FOXO1-mediated KLF2 suppression was reversed by atorvastatin, suggesting that
      intensive statin treatment could be a therapeutic option in diabetic vascular
      dysfunction.

PMID- 23002243
TI  - The effect of exercise training on left ventricular relaxation and diastolic
      suction at rest and during orthostatic stress after bed rest.
AB  - A marked reduction in upright stroke volume (SV) contributes substantially to
      orthostatic intolerance after exposure to spaceflight or bed rest. It is unclear
      whether slowed left ventricular (LV) relaxation and diastolic suction contribute
      to the reduction in SV or whether these changes are influenced by exercise
      training while in bed. Twenty-seven healthy adults completed 5 weeks of -6 deg
      head-down bed rest (HDBR). During HDBR, nine subjects were sedentary (NOEX),
      while 18 performed near-daily rowing ergometry (EX). Left ventricular mass, SV,
      LV end-diastolic volume (LVEDV), pulmonary capillary wedge pressure and Doppler
      ultrasound indices of LV function were collected pre- and post-HDBR during supine
      rest (twice) and during reduced LV loading (lower body negative pressure; LBNP)
      and increased LV loading (saline infusion). Post-HDBR, LV mass increased in the
      EX group, but decreased in the NOEX group. The reduction in SV and LVEDV during
      supine rest and LBNP were greater with NOEX in comparison to EX after HDBR. Peak
      early mitral annular velocity, isovolumic relaxation time, early propagation
      velocity, a non-invasive index of early diastolic filling and ventricular
      diastolic suction, and peak global longitudinal early strain rate were slowed
      during supine rest after HDBR with NOEX; however, these variables were either
      unaltered or the reduction was less prominent with EX. Doppler ultrasound
      measures of early diastolic filling, ventricular relaxation and diastolic suction
      were not significantly affected during LV unloading by LBNP after HDBR in either
      group. All Doppler indices were restored to pre-HDBR levels in both groups during
      saline infusion to normalize LV filling pressure after HDBR. It is concluded that
      Doppler indices of dynamic LV filling were reduced in both groups after HDBR;
      however, these effects were more pronounced in the NOEX group. Irrespective of
      group, post-HDBR Doppler parameters were restored when LV filling pressure was
      increased to pre-HDBR levels during saline infusion. Therefore, the reduction in
      upright SV after HDBR is more influenced by changes in LV loading conditions,
      namely left atrial pressure in the setting of LV remodelling, rather than
      ventricular relaxation and diastolic suction.

PMID- 23002244
TI  - The glutamatergic system as a target for neuropathic pain relief.
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian CNS. The
      understanding of glutamatergic transmission in the nervous system has been
      greatly expanded with the discovery and investigation of the family of ionotropic
      and metabotropic glutamate receptors (mGluRs). Metabotropic glutamate receptors
      are localized at nerve terminals, postsynaptic sites and glial cells and thus,
      they can influence and modulate the action of glutamate at different levels in
      the synapse. Moreover, there is substantial evidence of glial participation in
      glutamate nociceptive processes and neuropathic pain. Metabotropic glutamate
      receptors have been shown to play a role in neuropathic pain, which is one of the
      most troublesome illnesses because the therapy is still not satisfactory.
      Recently, the development of selective mGluR ligands has provided important tools
      for further investigation of the role of mGluRs in the modulation of chronic pain
      processing. This paper presents a review of the literature of glutamate receptors
      in neuropathic pain and the role of glia in these effects. Specifically,
      pharmacological interventions aimed at inhibiting group I mGluRs and/or
      potentiating group II and III mGluR-mediated signalling is discussed. Moreover,
      we introduce data about the role of glutamate transporters. They are responsible
      for the level of glutamate in the synaptic cleft and thus regulate the effects of
      all three groups of mGluRs and, in consequence, the activity of this system in
      nociceptive transmission. Additionally, the question of how the modulation of the
      glutamatergic system influences the effectiveness of analgesic drugs used in
      neuropathic pain therapy is addressed.

PMID- 23002245
TI  - Surgical retrieval of transected umbilical catheter from preterm infant.

PMID- 23002246
TI  - Matrix-bound heparan sulfate is essential for the growth and pluripotency of
      human embryonic stem cells.
AB  - Human embryonic stem (hES) cell production of heparan sulfate influences cell
      fate and pluripotency. Human ES cells remain pluripotent in vitro through the
      action of growth factors signaling, and the activity of these factors depends on
      interaction with specific receptors and also with heparan sulfate. Here, we
      tested the hypothesis that matrix-associated heparan sulfate is enough to
      maintain hES cells under low fibroblast growth factor-2 concentration in the
      absence of live feeder cells. To pursue this goal, we compared hES cells cultured
      either on coated plates containing live murine embryonic fibroblasts (MEFs) or on
      a matrix derived from ethanol-fixed MEFs. hES cells were analyzed for the
      expression of pluripotency markers and the ability to form embryoid bodies. hES
      cells cultured either on live mouse fibroblasts or onto a matrix derived from
      fixed fibroblasts expressed similar levels of Oct-4, SOX-2, Nanog, TRA-1-60 and
      SSEA-4, and they were also able to form cavitated embryoid bodies. Heparan
      sulfate-depleted matrix lost the ability to support the adherence and growth of
      hES cells, confirming that this glycosaminoglycan, bound to the extracellular
      matrix, is enough for the growth and attachment of hES cells. Finally, we
      observed that the ethanol-fixed matrix decreases by 30% the levels of Neu5Gc in
      hES cells, indicating that this procedure reduces xeno-contamination. Our data
      suggest that matrix-bound heparan sulfate is required for the growth and
      pluripotency of hES cells and that ethanol-fixed MEFs may be used as a "live
      cell"-free substrate for stem cells.

PMID- 23002247
TI  - Gata6 is required for complete acinar differentiation and maintenance of the
      exocrine pancreas in adult mice.
AB  - OBJECTIVES: Previous studies have suggested an important role of the
      transcription factor Gata6 in endocrine pancreas, while GATA6 haploinsufficient
      inactivating mutations cause pancreatic agenesis in humans. We aimed to analyse
      the effects of Gata6 inactivation on pancreas development and function. DESIGN:
      We deleted Gata6 in all epithelial cells in the murine pancreas at the onset of
      its development. Acinar proliferation, apoptosis, differentiation and exocrine
      functions were assessed using reverse transcriptase quantitative PCR (RT-qPCR),
      chromatin immunoprecipitation, immunohistochemistry and enzyme assays. Adipocyte
      transdifferentiation was assessed using electron microscopy and genetic lineage
      tracing. RESULTS: Gata6 is expressed in all epithelial cells in the adult mouse
      pancreas but it is only essential for exocrine pancreas homeostasis: while
      dispensable for pancreatic development after e10.5, it is required for complete
      acinar differentiation, for establishment of polarity and for the maintenance of
      acinar cells in the adult. Gata6 regulates directly the promoter of genes coding
      for digestive enzymes and the transcription factors Rbpjl and Mist1. Upon
      pancreas-selective Gata6 inactivation, massive loss of acinar cells and fat
      replacement take place. This is accompanied by increased acinar apoptosis and
      proliferation, acinar-to-ductal metaplasia and adipocyte transdifferentiation. By
      contrast, the endocrine pancreas is spared. CONCLUSIONS: Our data show that Gata6
      is required for the complete differentiation of acinar cells through multiple
      transcriptional regulatory mechanisms. In addition, it is required for the
      maintenance of the adult acinar cell compartment. Our studies suggest that GATA6
      alterations may contribute to diseases of the human adult exocrine pancreas.

PMID- 23002248
TI  - Priority setting and implementation in a centralized health system: a case study
      of Kerman province in Iran.
AB  - The question of how priority setting processes work remains topical, contentious
      and political in every health system across the globe. It is particularly acute
      in the context of developing countries because of the mismatch between needs and
      resources, which is often compounded by an underdeveloped capacity for decision
      making and weak institutional infrastructures. Yet there is limited research into
      how the process of setting and implementing health priorities works in developing
      countries. This study aims to address this gap by examining how a national
      priority setting programme works in the centralized health system of Iran and
      what factors influence its implementation at the meso and micro levels. We used a
      qualitative case study approach, incorporating mixed methods: in-depth interviews
      at three levels and a textual analysis of policy documents. The data analysis
      showed that the process of priority setting is non-systematic, there is little
      transparency as to how specific priorities are decided, and the decisions made
      are separated from their implementation. This is due to the highly centralized
      system, whereby health priorities are set at the macro level without involving
      meso or micro local levels or any representative of the public. Furthermore, the
      two main benefit packages are decided by different bodies (Ministry of Health and
      Medical Education and Ministry of Welfare and Social Security) and there is no co
      ordination between them. The process is also heavily influenced by political
      pressure exerted by various groups, mostly medical professionals who attempt to
      control priority setting in accordance with their interests. Finally, there are
      many weaknesses in the implementation of priorities, resulting in a growing gap
      between rural and urban areas in terms of access to health services. 

PMID- 23002249
TI  - Preparing routine health information systems for immediate health responses to
      disasters.
AB  - During disaster times, we need specific information to rapidly plan a disaster
      response, especially in sudden-onset disasters. Due to the inadequate capacity of
      Routine Health Information Systems (RHIS), many developing countries face a lack
      of quality pre-disaster health-related data and efficient post-disaster data
      processes in the immediate aftermath of a disaster. Considering the significance
      of local capacity during the early stages of disaster response, RHIS at local,
      provincial/state and national levels need to be strengthened so that they provide
      relief personnel up-to-date information to plan, organize and monitor immediate
      relief activities. RHIS professionals should be aware of specific information
      needs in disaster response (according to the Sphere Project's Humanitarian
      Minimum Standards) and requirements in data processes to fulfil those information
      needs. Preparing RHIS for disasters can be guided by key RHIS-strengthening
      frameworks; and disaster preparedness must be incorporated into countries' RHIS.
      Mechanisms must be established in non-disaster times and maintained between RHIS
      and information systems of non-health sectors for exchanging disaster-related
      information and sharing technologies and cost. 

PMID- 23002250
TI  - 'Avoidable' mortality: a measure of health system performance in the Czech
      Republic and Slovakia between 1971 and 2008.
AB  - BACKGROUND Post-communist health care reforms and the break-up of Czechoslovakia
      have been studied from various perspectives, but little research has addressed
      the impact on health system performance. This paper investigates the quality and
      performance of the Slovak and Czech health systems before and after 1989,
      including the year of separation in 1993, using the concept of 'avoidable'
      mortality. METHODS Age-standardized mortality rates for mortality from
      'avoidable' and other (non-avoidable) causes have been calculated through
      indirect standardization to study national and regional trends between 1971 and
      2008. RESULTS The paper shows that 'avoidable' mortality in both countries has
      been continuously decreasing while mortality from other causes has remained
      unchanged or increased slightly. For some 'avoidable' conditions, mortality rates
      of the two countries converge while for others divergence can be observed, with
      either the Czech Republic or Slovakia performing better. CONCLUSION Declines in
      overall 'avoidable' mortality suggest improvements in the health system's
      performance and quality of care in both countries, compared with mortality from
      other causes where factors outside the control of the health care system may be
      stronger determinants. For conditions where 'avoidable' mortality rates stagnate
      or increase, more in-depth research should be carried out to identify problems in
      the delivery of timely and effective prevention and treatment, and to establish
      steps that would reduce the numbers of unnecessary deaths. 

PMID- 23002251
TI  - Forecasting burden of long-term disability from neonatal conditions: results from
      the Projahnmo I trial, Sylhet, Bangladesh.
AB  - INTRODUCTION: The burden of disease resulting from neonatal conditions is
      substantial in developing countries. From 2003 to 2005, the Projahnmo I programme
      delivered community-based interventions for maternal and newborn health in
      Sylhet, Bangladesh. This analysis quantifies burden of disability and
      incorporates non-fatal outcomes into cost-effectiveness analysis of interventions
      delivered in the Projahnmo I programme. METHODS: A decision tree model was
      created to predict disability resulting from preterm birth, neonatal meningitis
      and intrapartum-related hypoxia ('birth asphyxia'). Outcomes were defined as the
      years lost to disability (YLD) component of disability-adjusted life years
      (DALYs). Calculations were based on data from the Projahnmo I trial, supplemented
      with values from published literature and expert opinion where data were absent.
      RESULTS: 195 YLD per 1000 neonates [95% confidence interval (CI): 157-241] were
      predicted in the main calculation, sensitive to different DALY assumptions,
      disability weights and alternative model structures. The Projahnmo I home care
      intervention may have averted 2.0 (1.3-2.8) YLD per 1000 neonates. Compared with
      calculations based on reductions in mortality alone, the cost-effectiveness ratio
      decreased by only 0.6% from $105.23 to $104.62 ($65.15-$266.60) when YLD were
      included, with 0.6% more DALYs averted [total 338/1000 (95% CI: 131-542)].
      DISCUSSION: A significant burden of disability results from neonatal conditions
      in Sylhet, Bangladesh. Adding YLD has very little impact on recommendations based
      on cost-effectiveness, even at the margin of programme adoption. This model
      provides guidance for collecting data on disabilities in new settings.

PMID- 23002252
TI  - Social marketing: approach to cultural and contextual relevance in a community
      based physical activity intervention.
AB  - We report the social marketing strategies used for the design, recruitment and
      retention of participants in a community-based physical activity (PA)
      intervention, Madres para la Salud (Mothers for Health). The study example used
      to illustrate the use of social marketing is a 48-week prescribed walking
      program, Madres para la Salud (Mothers for Health), which tests a social support
      intervention to explore the effectiveness of a culturally specific program using
      'bouts' of PA to effect the changes in body fat, fat tissue inflammation and
      postpartum depression symptoms in sedentary Hispanic women. Using the guidelines
      from the National Benchmark Criteria, we developed intervention, recruitment and
      retention strategies that reflect efforts to draw on community values, traditions
      and customs in intervention design, through partnership with community members.
      Most of the women enrolled in Madres para la Salud were born in Mexico, largely
      never or unemployed and resided among the highest crime neighborhoods with poor
      access to resources. We developed recruitment and retention strategies that
      characterized social marketing strategies that employed a culturally relevant,
      consumer driven and problem-specific design. Cost and benefit of program
      participation, consumer-derived motivation and segmentation strategies considered
      the development transition of the young Latinas as well as cultural and
      neighborhood barriers that impacted retention are described. 

PMID- 23002253
TI  - Evaluation of the NICE mini-GRACE risk scores for acute myocardial infarction
      using the Myocardial Ischaemia National Audit Project (MINAP) 2003-2009: National
      Institute for Cardiovascular Outcomes Research (NICOR).
AB  - OBJECTIVE: To evaluate the performance of the National Institute for Health and
      Clinical Excellence (NICE) mini-Global Registry of Acute Coronary Events (GRACE)
      (MG) and adjusted mini-GRACE (AMG) risk scores. DESIGN: Retrospective
      observational study. SETTING: 215 acute hospitals in England and Wales. PATIENTS:
      137 084 patients discharged from hospital with a diagnosis of acute myocardial
      infarction (AMI) between 2003 and 2009, as recorded in the Myocardial Ischaemia
      National Audit Project (MINAP). MAIN OUTCOME MEASURES: Model performance indices
      of calibration accuracy, discriminative and explanatory performance, including
      net reclassification index (NRI) and integrated discrimination improvement.
      RESULTS: Of 495 263 index patients hospitalised with AMI, there were 53 196 ST
      elevation myocardial infarction and 83 888 non-ST elevation myocardial infarction
      (NSTEMI) (27.7%) cases with complete data for all AMG variables. For AMI, AMG
      calibration was better than MG calibration (Hosmer-Lemeshow goodness of fit test:
      p=0.33 vs p<0.05). MG and AMG predictive accuracy and discriminative ability were
      good (Brier score: 0.10 vs 0.09; C statistic: 0.82 and 0.84, respectively). The
      NRI of AMG over MG was 8.1% (p<0.05). Model performance was reduced in patients
      with NSTEMI, chronic heart failure, chronic renal failure and in patients aged
      >=85 years. CONCLUSIONS: The AMG and MG risk scores, utilised by NICE,
      demonstrated good performance across a range of indices using MINAP data, but
      performed less well in higher risk subgroups. Although indices were better for
      AMG, its application may be constrained by missing predictors.

PMID- 23002254
TI  - An ounce of prevention is worth a pound of cure...as well as a pound of cash.

PMID- 23002255
TI  - Regional anesthesia: then and now.

PMID- 23002257
TI  - Middle cerebral arterial blood flow velocity increases during laparoscopic
      cholecystectomy: retraction.

PMID- 23002258
TI  - The effects of dexamethasone on antiemetics in female patients undergoing
      gynecologic surgery: retraction.

PMID- 23002259
TI  - Lateral injection using a Whitacre needle with patients in the lateral decubitus
      position maintained for a prolonged time period produces symmetric sensory block.
AB  - BACKGROUND: The directional flow of injection through a Whitacre needle can be
      used to modify the level of sensory blockade. We hypothesized that injection of
      hyperbaric local anesthetic through a Whitacre needle with the bevel oriented
      laterally can produce a more symmetric sensory block. METHODS: Patients scheduled
      for lower limb surgery under spinal anesthesia with the patient in lateral
      decubitus position were randomized to receive 10 mg, 0.5% hyperbaric bupivacaine
      with the Whitacre needle orifice in 1 of 2 orientations, cephalad and lateral.
      The patient's position was maintained for 15 min after the injection, and sensory
      blocks were recorded. The primary outcome was the sensory levels between the
      dependent and nondependent side. The Wilcoxon-Mann-Whitney U-test odds was used
      to compare unpaired nonparametric data. For the paired samples, 95% confidence
      intervals (CI) of differences between group medians were calculated using the
      Hodges-Lehman estimator for the median difference in number of blocked segments.
      RESULTS: There was no significant difference in block level between dependent and
      nondependent sides in the lateral group. The Hodges-Lehmann point estimator was
      0.5% and 95% CI was 0-2.5, suggesting a more symmetric sensory block in patients
      in the lateral decubitus position maintained for a sufficient period of time. A
      significantly lower level of blockade was noticed on the nondependent side
      compared to the dependent side in the cephalad group. The Hodges-Lehmann point
      estimator was 2.5 segments and 95% CI was 0.5-5. CONCLUSIONS: Injection of 10 mg
      of 0.5% hyperbaric bupivacaine with the bevel of the Whitacre needle oriented
      laterally produces more symmetric sensory levels of blockade between the
      dependent and nondependent sides.

PMID- 23002260
TI  - The ulinastatin-induced effect on neuromuscular block caused by vecuronium:
      retraction.

PMID- 23002261
TI  - When similar is not alike: decreased sensory thresholds after intravenous
      infusion of remifentanil may not be remifentanil-induced hyperalgesia.

PMID- 23002262
TI  - Immediate and delayed remifentanil-induced hypersensitivity.

PMID- 23002263
TI  - Considering the importance of power calculations.

PMID- 23002264
TI  - High oxygen flow can create a powerful anterograde water stream when utilizing a
      bubble-over humidification system.

PMID- 23002265
TI  - Clear surgical drapes: a technique to facilitate the "natural cesarean delivery".

PMID- 23002266
TI  - Editor's note: notices of retraction.

PMID- 23002267
TI  - Minority cytotypes in European populations of the Gymnadenia conopsea complex
      (Orchidaceae) greatly increase intraspecific and intrapopulation diversity.
AB  - BACKGROUND AND AIMS: Patterns of ploidy variation among and within populations
      can provide valuable insights into the evolutionary mechanisms shaping the
      dynamics of plant systems showing ploidy diversity. Whereas data on majority
      ploidies are, by definition, often sufficiently extensive, much less is known
      about the incidence and evolutionary role of minority cytotypes. METHODS: Ploidy
      and proportions of endoreplicated genome were determined using DAPI (4',6
      diamidino-2-phenylindole) flow cytometry in 6150 Gymnadenia plants (fragrant
      orchids) collected from 141 populations in 17 European countries. All widely
      recognized European species, and several taxa of less certain taxonomic status
      were sampled within Gymnadenia conopsea sensu lato. KEY RESULTS: Most Gymnadenia
      populations were taxonomically and/or ploidy heterogeneous. Two majority (2x and
      4x) and three minority (3x, 5x and 6x) cytotypes were identified. Evolution
      largely proceeded at the diploid level, whereas tetraploids were much more
      geographically and taxonomically restricted. Although minority ploidies
      constituted <2 % of the individuals sampled, they were found in 35 % of
      populations across the entire area investigated. The amount of nuclear DNA,
      together with the level of progressively partial endoreplication, separated all
      Gymnadenia species currently widely recognized in Europe. CONCLUSIONS: Despite
      their low frequency, minority cytotypes substantially increase intraspecific and
      intrapopulation ploidy diversity estimates for fragrant orchids. The cytogenetic
      structure of Gymnadenia populations is remarkably dynamic and shaped by multiple
      evolutionary mechanisms, including both the ongoing production of unreduced
      gametes and heteroploid hybridization. Overall, it is likely that the level of
      ploidy heterogeneity experienced by most plant species/populations is currently
      underestimated; intensive sampling is necessary to obtain a holistic picture.

PMID- 23002268
TI  - Selection for low dormancy in annual ryegrass (Lolium rigidum) seeds results in
      high constitutive expression of a glucose-responsive alpha-amylase isoform.
AB  - BACKGROUND AND AIMS: alpha-Amylase in grass caryopses (seeds) is usually
      expressed upon commencement of germination and is rarely seen in dry, mature
      seeds. A heat-stable alpha-amylase activity was unexpectedly selected for
      expression in dry annual ryegrass (Lolium rigidum) seeds during targeted
      selection for low primary dormancy. The aim of this study was to characterize
      this constitutive activity biochemically and determine if its presence conferred
      insensitivity to the germination inhibitors abscisic acid and benzoxazolinone.
      METHODS: alpha-Amylase activity in developing, mature and germinating seeds from
      the selected (low-dormancy) and a field-collected (dormant) population was
      characterized by native activity PAGE. The response of seed germination and alpha
      amylase activity to abscisic acid and benzoxazolinone was assessed. Using an
      alginate affinity matrix, alpha-amylase was purified from dry and germinating
      seeds for analysis of its enzymatic properties. KEY RESULTS: The constitutive
      alpha-amylase activity appeared late during seed development and was mainly
      localized in the aleurone; in germinating seeds, this activity was responsive to
      both glucose and gibberellin. It migrated differently on native PAGE compared
      with the major activities in germinating seeds of the dormant population, but the
      enzymatic properties of alpha-amylase purified from the low-dormancy and dormant
      seeds were largely indistinguishable. Seed imbibition on benzoxazolinone had
      little effect on the low-dormancy seeds but greatly inhibited germination and
      alpha-amylase activity in the dormant population. CONCLUSIONS: The constitutive
      alpha-amylase activity in annual ryegrass seeds selected for low dormancy is
      electrophoretically different from that in germinating seeds and its presence
      confers insensitivity to benzoxazolinone. The concurrent selection of low
      dormancy and constitutive alpha-amylase activity may help to enhance seedling
      establishment under competitive conditions.

PMID- 23002269
TI  - Decrease of sexual organ reciprocity between heterostylous primrose species, with
      possible functional and evolutionary implications.
AB  - BACKGROUND AND AIMS: Heterostyly is a floral polymorphism that has fascinated
      evolutionary biologists since Darwin's seminal studies on primroses. The main
      morphological characteristic of heterostyly is the reciprocal placement of
      anthers and stigmas in two distinct (distyly) floral morphs. Variation in the
      degree of intermorph sexual reciprocity is relatively common and known to affect
      patterns of pollen transfer within species. However, the partitioning of sexual
      organ reciprocity within and between closely related species remains unknown.
      This study aimed at testing whether intermorph sexual reciprocity differs within
      vs. between primrose species that hybridize in nature and whether the positions
      of sexual organs are correlated with other floral traits. METHODS: Six floral
      traits were measured in both floral morphs of 15 allopatric populations of
      Primula elatior, P. veris and P. vulgaris, and anther-stigma reciprocity was
      estimated within and between species. A combination of univariate and
      multivariate approaches was used to test whether positions of reproductive organs
      were less reciprocal between than within species, to assess correlations between
      sexual organ positions and other corolla traits, and to quantify differences
      between morphs and species. KEY RESULTS: The three species were morphologically
      well differentiated in most floral traits, except that P. veris and P. vulgaris
      did not differ significantly in sexual organ positions. Overall, lower
      interspecific than intraspecific sexual organ reciprocity was detected. This
      decrease was marked between P. elatior and P. vulgaris, intermediate and variable
      between P. elatior and P. veris, but negligible between P. veris and P. vulgaris.
      CONCLUSIONS: Differences in anther and stigma heights between the analysed
      primrose species were of the same magnitude or larger than intraspecific
      differences that altered pollen flow within other heterostylous systems.
      Therefore, it is possible to suggest that considerable reductions of sexual organ
      reciprocity between species may lower interspecific pollen flow, with potential
      effects on reproductive isolation.

PMID- 23002270
TI  - The role of grasslands in food security and climate change.
AB  - BACKGROUND: Grasslands are a major part of the global ecosystem, covering 37 % of
      the earth's terrestrial area. For a variety of reasons, mostly related to
      overgrazing and the resulting problems of soil erosion and weed encroachment,
      many of the world's natural grasslands are in poor condition and showing signs of
      degradation. This review examines their contribution to global food supply and to
      combating climate change. SCOPE: Grasslands make a significant contribution to
      food security through providing part of the feed requirements of ruminants used
      for meat and milk production. Globally, this is more important in food energy
      terms than pig meat and poultry meat. Grasslands are considered to have the
      potential to play a key role in greenhouse gas mitigation, particularly in terms
      of global carbon storage and further carbon sequestration. It is estimated that
      grazing land management and pasture improvement (e.g. through managing grazing
      intensity, improved productivity, etc) have a global technical mitigation
      potential of almost 1.5 Gt CO(2) equivalent in 2030, with additional mitigation
      possible from restoration of degraded lands. Milk and meat production from
      grassland systems in temperate regions has similar emissions of carbon dioxide
      per kilogram of product as mixed farming systems in temperate regions, and, if
      carbon sinks in grasslands are taken into account, grassland-based production
      systems can be as efficient as high-input systems from a greenhouse gas
      perspective. CONCLUSIONS: Grasslands are important for global food supply,
      contributing to ruminant milk and meat production. Extra food will need to come
      from the world's existing agricultural land base (including grasslands) as the
      total area of agricultural land has remained static since 1991. Ruminants are
      efficient converters of grass into humanly edible energy and protein and
      grassland-based food production can produce food with a comparable carbon
      footprint as mixed systems. Grasslands are a very important store of carbon, and
      they are continuing to sequester carbon with considerable potential to increase
      this further. Grassland adaptation to climate change will be variable, with
      possible increases or decreases in productivity and increases or decreases in
      soil carbon stores.

PMID- 23002271
TI  - Unravelling genetics at the top: mountain islands or isolated belts?
AB  - BACKGROUND AND AIMS: In mountain plant populations, local adaptation has been
      described as one of the main responses to climate warming, allowing plants to
      persist under stressful conditions. This is especially the case for marginal
      populations at their lowest elevation, as they are highly vulnerable. Adequate
      levels of genetic diversity are required for selection to take place, while high
      levels of altitudinal gene flow are seen as a major limiting factor potentially
      precluding local adaptation processes. Thus, a compromise between genetic
      diversity and gene flow seems necessary to guarantee persistence under oncoming
      conditions. It is therefore critical to determine if gene flow occurs
      preferentially between mountains at similar altitudinal belts, promoting local
      adaptation at the lowest populations, or conversely along altitude within each
      mountain. METHODS: Microsatellite markers were used to unravel genetic diversity
      and population structure, inbreeding and gene flow of populations at two nearby
      altitudinal gradients of Silene ciliata, a Mediterranean high-mountain cushion
      plant. KEY RESULTS: Genetic diversity and inbreeding coefficients were similar in
      all populations. Substantial gene flow was found both along altitudinal gradients
      and horizontally within each elevation belt, although greater values were
      obtained along altitudinal gradients. Gene flow may be responsible for the
      homogeneous levels of genetic diversity found among populations. Bayesian cluster
      analyses also suggested that shifts along altitudinal gradients are the most
      plausible scenario. CONCLUSIONS: Past population shifts associated with
      glaciations and interglacial periods in temperate mountains may partially explain
      current distributions of genetic diversity and population structure. In spite of
      the predominance of gene flow along the altitudinal gradients, local genetic
      differentiation of one of the lower populations together with the detection of
      one outlier locus might support the existence of different selection forces at
      low altitudes.

PMID- 23002273
TI  - Evaluation of recommended REACH exposure modeling tools and near-field, far-field
      model in assessing occupational exposure to toluene from spray paint.
AB  - Predictive modeling is an available tool to assess worker exposures to a variety
      of chemicals in different industries and product-use scenarios. The European
      Chemical Agency (ECHA)'s guidelines for manufacturers to fulfill the European
      Union's legal requirements pursuant to the Registration, Evaluation,
      Authorization, and Restriction of Chemicals (REACH) initiative include
      recommendations for the use of modeling to predict worker exposures. ECHA
      recommends different models for different target populations (i.e. workers,
      consumers, environment) and routes of exposure (i.e. skin absorption, ingestion,
      inhalation), and presents them hierarchically, with Tier 1 models presented as
      the most simplistic, conservative models and Tier 2 models recommended for
      further intensive evaluation of substances or preparations. In order to assess
      these models for one exposure (product-use) scenario, a simulation of the
      scenario was completed in a controlled environment and the measured results were
      compared with the modeling outputs. The authors predicted, based on the design of
      the modeling tools, that all models would overestimate worker exposures under the
      simulated product-use scenario, with the lower-tiered model producing the most
      conservative estimate of exposure. In this study, a Tier 1 model and a Tier 2
      model were evaluated for comparison with the near-field, far-field (NF-FF)
      deterministic model and measured experimental results in a real-time worker
      inhalation exposure assessment. Modeling was conducted prior to actual air
      monitoring. The exposure scenario that was evaluated involved the application of
      a toluene-containing spray paint to a work surface. Air samples were collected to
      evaluate short-term (15-min) and long-term (240-min) exposures. Eight-hour time
      weighted averages (8-h TWAs) were calculated and compared with the modeling
      outputs from the recommended REACH modeling tools and the NF-FF model. A
      comparison of each of the modeling tools with measured experimental results was
      generated. The Tier 1 Targeted Risk Assessment tool overestimated the 8-h TWA
      airborne concentration of toluene in the spray scenario by a factor of 3.61. The
      higher tiered Advanced REACH Tool and NF-FF models showed greater concordance
      with experimental results, overestimating the TWA exposure by a factor of 2.92
      and 1.96, respectively. In conclusion, the Tier 1 and 2 exposure modeling tools
      performed as expected for the simulated exposure scenario, providing relatively
      accurate, though conservative, estimates according to the level of detail and
      precision accounted for in each model.

PMID- 23002272
TI  - Genetic differentiation for size at first reproduction through male versus female
      functions in the widespread Mediterranean tree Pinus pinaster.
AB  - BACKGROUND AND AIMS: The study of local adaptation in plant reproductive traits
      has received substantial attention in short-lived species, but studies conducted
      on forest trees are scarce. This lack of research on long-lived species
      represents an important gap in our knowledge, because inferences about selection
      on the reproduction and life history of short-lived species cannot necessarily be
      extrapolated to trees. This study considers whether the size for first
      reproduction is locally adapted across a broad geographical range of the
      Mediterranean conifer species Pinus pinaster. In particular, the study
      investigates whether this monoecious species varies genetically among populations
      in terms of whether individuals start to reproduce through their male function,
      their female function or both sexual functions simultaneously. Whether
      differences among populations could be attributed to local adaptation across a
      climatic gradient is then considered. METHODS: Male and female reproduction and
      growth were measured during early stages of sexual maturity of a P. pinaster
      common garden comprising 23 populations sampled across the species range.
      Generalized linear mixed models were used to assess genetic variability of early
      reproductive life-history traits. Environmental correlations with reproductive
      life-history traits were tested after controlling for neutral genetic structure
      provided by 12 nuclear simple sequence repeat markers. KEY RESULTS: Trees tended
      to reproduce first through their male function, at a size (height) that varied
      little among source populations. The transition to female reproduction was
      slower, showed higher levels of variability and was negatively correlated with
      vegetative growth traits. Several female reproductive traits were correlated with
      a gradient of growth conditions, even after accounting for neutral genetic
      structure, with populations from more unfavourable sites tending to commence
      female reproduction at a lower individual size. CONCLUSIONS: The study represents
      the first report of genetic variability among populations for differences in the
      threshold size for first reproduction between male and female sexual functions in
      a tree species. The relatively uniform size at which individuals begin
      reproducing through their male function probably represents the fact that pollen
      dispersal is also relatively invariant among sites. However, the genetic
      variability in the timing of female reproduction probably reflects environment
      dependent costs of cone production. The results also suggest that early sex
      allocation in this species might evolve under constraints that do not apply to
      other conifers.

PMID- 23002274
TI  - Using urinary biomarkers of polycyclic aromatic compound exposure to guide
      exposure-reduction strategies among asphalt paving workers.
AB  - INTRODUCTION: Paving workers are exposed to polycyclic aromatic compounds (PACs)
      while working with hot-mix asphalt (HMA). Further characterization of the source
      and route of these exposures is necessary to guide exposure-reduction strategies.
      METHODS: Personal air (n=144), hand-wash (n=144), and urine (n=480) samples were
      collected from 12 paving workers over 3 workdays during 4 workweeks. Urine
      samples were collected at preshift, postshift, and bedtime and analyzed for 10
      hydroxylated PACs (1-OH-pyrene; 1-, 2-, 3-, 4-OH-phenanthrene; 1-, 2-OH
      naphthalene; 2-, 3-, 9-OH-fluorene) by an immunochemical quantification of PACs
      (I-PACs). The air and hand-wash samples were analyzed for the parent compounds
      corresponding to the urinary analytes. Using a crossover study design, each of
      the 4 weeks represented a different exposure scenario: a baseline week (normal
      conditions), a dermal protection week (protective clothing), a powered air
      purifying respirator (PAPR) week, and a biodiesel substitution week (100%
      biodiesel provided to replace the diesel oil normally used by workers to clean
      tools and equipment). The urinary analytes were analyzed using linear mixed
      effects models. RESULTS: Postshift and bedtime concentrations were significantly
      higher than preshift concentrations for most urinary biomarkers. Compared with
      baseline, urinary analytes were reduced during the dermal protection (29% for 1
      OH-pyrene, 15% for I-PACs), the PAPR (24% for 1-OH-pyrene, 15% for I-PACs), and
      the biodiesel substitution (15% for 1-OH-pyrene) weeks. The effect of PACs in air
      was different by exposure scenario (biodiesel substitution>dermal protection>PAPR
      and baseline) and was still a significant predictor of most urinary analytes
      during the week of PAPR use, suggesting that PACs in air were dermally absorbed.
      The application temperature of HMA was positively associated with urinary
      measures, such that an increase from the lowest application temperature (121
      degrees C) to the highest (154 degrees C) was associated with a 72% increase in
      SigmaOH-fluorene and 1-OH-pyrene and an 82% increase in SigmaOH-phenanthrene.
      Though PACs in hand-wash samples were not predictors of urinary analytes, the
      effects observed during the PAPR scenario and the week of increased dermal
      protection provide evidence of dermal absorption. CONCLUSIONS: Our results
      provide evidence that PACs in air are dermally absorbed. Reducing the application
      temperature of asphalt mix appears to be a promising strategy for reducing PAC
      exposure among paving workers. Additional reductions may be achieved by requiring
      increased dermal coverage of workers and by substituting biodiesel for diesel oil
      as a cleaning agent.

PMID- 23002275
TI  - Quality of evidence must guide risk assessment of asbestos.
AB  - In 2011, we reported on the sensitivity of lung cancer potency estimates for
      asbestos to the quality of the exposure assessment component of underlying
      evidence. Both this meta-analysis and a separate reassessment of standards
      published by the Health Council of the Netherlands (Gezondheidsraad) have been
      commented on by Berman and Case. A criticism is that we used a truncated data
      set. We incrementally excluded poorer-quality studies to evaluate trends in meta
      analyzed lung cancer potency estimates (meta-K   (L) values). This was one of
      three analysis approaches we presented. The other two used the full set of
      studies: a meta-analysis stratified by covariates and dichotomized by poorer and
      better exposure assessment aspects; and a meta-regression modeling both asbestos
      fiber type and these covariates. They also state that our results are not robust
      to removal of one study. We disagree with this claim and present additional
      sensitivity analyses underpinning our earlier conclusion that inclusion of
      studies with higher-quality asbestos-exposure assessment yield higher meta
      estimates of the lung cancer risk per unit of exposure. We reiterate that potency
      differences for predominantly chrysotile- versus amphibole-asbestos-exposed
      cohorts are difficult to ascertain when meta-analyses are restricted to studies
      with fewer exposure assessment limitations. We strongly argue that the existence
      of any uncertainty related to potency issues should not hamper the development of
      appropriate evidence-based guidelines and stringent policies in order to protect
      the public from hazardous environmental and occupational exposures.

PMID- 23002276
TI  - Association between occupational exposure and control measures for antineoplastic
      drugs in a pharmacy of a hospital.
AB  - OBJECTIVES: To investigate the association between occupational contamination and
      exposure levels to antineoplastic drugs and the application of control measures
      in a hospital work environment. METHODS: Wipe samples of equipments were
      collected at a hospital in Osaka Prefecture, Japan, from 2007 to 2011. These
      samples were subjected to measurements of cyclophosphamide (CP), gemcitabine
      (GEM), platinum-containing drugs (Pt), and fluorouracil (5FU). Additionally, 24-h
      urine samples were collected from pharmacists who handled antineoplastic drugs,
      which were analyzed for CP and alpha-fluoro-beta-alanine (AFBA). The application
      of control measures was scored according to a checklist, which consisted of the
      following five items: safety equipment and maintenance, training and
      documentation, devices for safe handling, personal protective equipment, and
      emergency care. The aim was to obtain a score of 80%. RESULTS: The median CP,
      GEM, and 5FU concentrations of all wipe samples were significantly lower during
      the period when the mean score was >80% (attainment period) versus when the mean
      score was <=80% (nonattainment period; all P < 0.001, Mann-Whitney's U-test).
      Additionally, the median urinary CP and AFBA concentrations of pharmacists during
      the attainment period tended to be lower than that of those during the
      nonattainment period (P = 0.061 and 0.061, respectively, using Mann-Whitney's U
      test). CONCLUSIONS: Contamination and levels of exposure to antineoplastic drugs
      decreased with a score higher than 80%. The scores of the items on the checklist
      appeared to adequately reflect the condition of the control measures, as
      increases in all five items were associated with reductions in the contamination
      by and levels of exposure to all drugs.

PMID- 23002277
TI  - Measurement of endotoxins in bioaerosols at workplace: a critical review of
      literature and a standardization issue.
AB  - Endotoxins are lipopolysaccharides found in the outer membrane of most Gram
      negative bacteria and cyanobacteria. Worker exposure to endotoxins has been shown
      in a number of work situations and is associated with both respiratory and
      systemic pathologies. The lack of an occupational exposure limit is mainly due to
      the absence of a standard protocol at the international level for sampling and
      analyzing airborne endotoxins. The bibliographic review in this article takes an
      exhaustive look at the current knowledge on measuring airborne endotoxins. It
      shows that, despite several reference documents at the international level, the
      methods used to measure endotoxin exposure differ considerably from one
      laboratory to another. Standardization is necessary to reduce interlaboratory
      variability and, ultimately, to improve the use of interstudy data. The
      bibliographic review presents the current status of standardization for airborne
      endotoxin measurement methods in the workplace and summarizes areas for further
      research. This article is both a reference document for all operators wishing to
      use such methods and a working document to build international consensus around
      the measurement of airborne endotoxins.

PMID- 23002279
TI  - Hope: oncology's missing breakthrough.

PMID- 23002278
TI  - Risk factors for local and regional recurrence in patients with resected N0-N1
      non-small-cell lung cancer, with implications for patient selection for adjuvant
      radiation therapy.
AB  - BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local
      and regional failure in patients with completely resected non-small-cell lung
      cancer (NSCLC), and to assess surgical and pathological factors affecting this
      risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402
      consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection
      without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS:
      Local-regional recurrence was identified in 9% of patients, with local failure
      alone in 3% of patients, regional failure alone in 4% of patients, and both local
      and regional failure simultaneously in 2% of patients. Patients who had local
      failure were found to be at increased risk of mortality. By multivariate
      analyses, three variables were shown to be independently significant risk factors
      for local [surgical procedure (single/multiple wedges+segmentectomy versus
      lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural
      invasion] and regional (pathologic N1 stage, visceral pleural invasion, and
      lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION:
      Patients with N0-N1 disease have low rates of locoregional recurrence after
      surgical resection. However, several prognostic factors can be identified that
      increase this risk and identify patients who may benefit from adjuvant treatment.

PMID- 23002280
TI  - Prognostic value of metabolic tumor volume measured by 18F-FDG PET/CT in advanced
      stage squamous cell carcinoma of the larynx and hypopharynx.
AB  - BACKGROUND: Metabolic tumor volume (MTV) of (18)F-FDG PET/CT is a volumetric
      measurement of tumor cells with increased 18F-FDG uptake. We evaluated the
      prognostic value of MTV in patients with locoregionally advanced laryngeal and
      hypopharyngeal cancer. PATIENTS AND METHODS: We evaluated 81 patients with
      advanced-stage squamous cell carcinoma of the laryngohypopharynx who underwent
      18F-FDG PET/CT between January 2004 and September 2009. Clinicopathologic factors
      and MTV were analyzed for their association with locoregional control (LRC) and
      overall survival (OS). RESULTS: The 3-year LRC and OS for all patients were 70.9
      and 78.7%, respectively, with a median follow-up of 40.4 months (range 24.5
      90.1). In univariate analyses, MTV, primary site, and primary treatment strategy
      were associated with both LRC and OS (P<0.05). On multivariate analysis, MTV was
      an independent prognostic factor for both LRC [P=0.018; HR=3.141, 95% confidence
      interval (CI)=1.175-8.399] and OS (P=0.008; HR=3.758, 95% CI=1.415-9.982).
      Primary site was also a significant prognostic factor for LRC (P=0.047).
      CONCLUSION: Pretreatment MTV is an independent prognostic factor in patients with
      locoregionally advanced squamous cell carcinoma of the larynx and hypopharynx.

PMID- 23002281
TI  - Discordance in receptor status between primary and recurrent breast cancer has a
      prognostic impact: a single-institution analysis.
AB  - BACKGROUND: Tumor phenotype may change during breast cancer progression. This
      study evaluates the prognostic impact of receptor discordance between paired
      primaries and recurrences. PATIENTS AND METHODS: One hundred and thirty-nine
      patients underwent histological sampling of suspected breast cancer recurrence.
      All the pathology assessments [ER, PgR and human epidermal growth factor receptor
      2 (HER2)] on both primaries and confirmed recurrences were performed at the same
      laboratory. RESULTS: A breast cancer recurrence was confirmed in 119 cases. Rates
      of discordance were 13.4%, 39% and 11.8% for ER, PgR and HER2, respectively.
      Ninety-two patients maintained the same tumor phenotype [i.e. the same hormone
      receptors (HR) and HER2 status], whereas 27 (22.7%) changed during progression.
      The loss of HR positivity and the loss of HER2 positivity resulted in a worse
      post-recurrence survival (P=0.01 and P=0.008, respectively) and overall survival
      (OS; P=0.06 and P=0.0002, respectively), compared with the corresponding
      concordant-positive cases. Tumor phenotype discordance was associated with worse
      post-recurrence and OS (P=0.006 and P=0.002, respectively); those cases who
      turned into triple-negative experienced the poorest outcome, respect to the
      concordant group (P=0.001, OS). CONCLUSIONS: We demonstrated for the first time
      an impact on OS of phenotype discordance between primary breast cancer and
      relapse. Among discordant cases, receptor loss resulted in the main determinant
      of poorer outcome.

PMID- 23002282
TI  - A randomized phase II study evaluating the combination of carboplatin-based
      chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients
      with relapsed, platinum-sensitive ovarian cancer.
AB  - BACKGROUND: Pertuzumab, a humanized monoclonal antibody targeting human epidermal
      growth factor receptor (HER)-mediated signalling, has shown activity in ovarian
      cancer in preclinical models and in the clinic. This randomized phase II study
      evaluated efficacy and safety of pertuzumab in combination with carboplatin-based
      chemotherapy in patients with platinum-sensitive, recurrent advanced ovarian
      cancer. PATIENTS AND METHODS: Patients were randomized to receive six cycles of
      chemotherapy (carboplatin and either paclitaxel (Taxol) or gemcitabine) with or
      without pertuzumab. The primary end point was progression-free survival (PFS) as
      determined by Response Evaluation Criteria in Solid Tumors and/or by CA 125
      measurements. Secondary end points evaluated the response rate, safety profile,
      duration of response, time to progression and overall survival for both treatment
      arms. RESULTS: A total of 149 patients received either chemotherapy with
      pertuzumab (arm A, n=74) or chemotherapy alone (arm B, n=75). There was no
      significant difference either in median PFS or in the secondary end points
      between the two arms. No differences were seen in an exploratory biomarker
      analysis of HER3 mRNA expression between the two arms. Pertuzumab was well
      tolerated, with no increase in cardiac adverse events compared with chemotherapy
      alone. CONCLUSIONS: The addition of pertuzumab to carboplatin-based chemotherapy
      did not substantially prolong PFS in unselected patients with platinum-sensitive
      ovarian cancer.

PMID- 23002283
TI  - Abnormalities of serum-free light chain in patients with primary antibody
      deficiency in the absence of B lymphocyte clonality.
AB  - AIMS: A review of practice to determine whether serum-free light chain (SFLC)
      assays are helpful in detecting underlying clonal B-cell disorders or amyloidosis
      in patients with primary antibody deficiency (PAD) and recurrent infection.
      METHODS: SFLC were assayed by nephelometry (BN2 nephelometer, Siemens; FREELITE
      assay, Binding Site). We reviewed SFLC test results recorded in our regional
      laboratory over a 4-year time period; 20 adults with PAD were identified as
      having been tested on at least two occasions. RESULTS: Of 20 patients, 4 with PAD
      had abnormal serum-free kappa/lambda (K/L) ratios but no evidence of B-cell
      clonality. We also found extremely low levels of kappa and or lambda (below the
      limits of reliable detection) in 19/20 PAD cases (mostly common variable
      immunodeficiency), such that in many, ratios were not calculable. CONCLUSIONS:
      The data suggest that the abnormal ratios are generated by an inability to
      produce and/or secrete SFLCs, particularly kappa FLC. In this small initial
      study, we seek to highlight PAD cases where a suspicious K/L ratio, typically
      with very low absolute quantities of SFLCs, most likely points to B-cell
      dysfunction, rather than to B lymphocyte clonality.

PMID- 23002284
TI  - Immunohistochemistry in the era of personalised medicine.
AB  - BACKGROUND: Immunohistochemistry (IHC) plays a central role in the
      histopathological classification of diseases, including cancer. More recently,
      the importance of immunohistochemical staining is increasing. IHC usage in
      diagnostics is invaluable; however, the genetic and therapeutic significance of
      biomarker immunostaining has become equally relevant. CONTENT: In this article,
      we would like to analyse the three distinct roles of IHC and review their
      individual impacts on modern diagnostic pathology: (1) diagnostic IHC; (2)
      genetic IHC and (3) therapeutic IHC. SUMMARY: Thus, we will characterise the
      different analytical processes that are required in the three approaches to IHC
      usage stated above, as well as the clinical significance and overall importance
      in patient management. This will allow us to hypothesise on the most appropriate
      laboratory environment and detection methods for the future.

PMID- 23002285
TI  - Diagnostic and prognostic impact of desmocollins in human lung cancer.
AB  - OBJECTIVE: Desmosomes are intercellular junctions that confer strong cell-cell
      adhesion. Two main members of desmosomal cadherins, desmogleins (DSGs) and
      desmocollins (DSCs), are involved in carcinogenesis. However, their role in human
      lung cancer remained elusive. The aims of this study were to analyse the
      expression of DSCs and to evaluate their clinical application in lung cancer.
      METHODS: The expression of DSC1-3 mRNAs was analysed by RT-PCR. The methylation
      status of DSCs was analysed by demethylation tests and bisulphite sequencing.
      Protein expression of DSCs in primary lung cancer was evaluated by
      immunohistochemistry on tissue microarrays. RESULTS: DSC1-3 mRNAs were
      downregulated in lung cancer cells, and the expression was restored in four out
      of seven cell lines, respectively, after 5-aza-2'-deoxycytidine treatment. A
      heterogeneous methylation pattern was detected by bisulphite sequencing in exon 1
      of DSC2 and DSC3. In 199 patients with primary lung cancer, we found that lower
      protein expression of DSC1 was significantly linked to worse tumour
      differentiation (p=0.017), DSC3 proteins were more expressed in squamous cell
      carcinoma (SCC) compared with adenocarcinoma (ADC) (p<0.001), and reduced
      expression of DSC1 and DSC3 was significantly correlated with poor clinical
      outcome (p=0.045 and p=0.007, respectively). CONCLUSIONS: Our data suggest that
      downregulation of DSC1-3 may be explained by DNA methylation, DSC1 may be a
      marker for tumour differentiation, DSC3 has a potential diagnostic value in
      subclassification of non-small cell lung carcinoma into SCC and ADC, and
      furthermore, DSC1 and DSC3 may be prognostic markers for lung cancer.

PMID- 23002287
TI  - Survival and causes of death among released brown hares (Lepus europaeus Pallas,
      1778) in Central Poland.
AB  - We describe the results of our research on population dynamics among brown hares
      reared in enclosures and then released into suitable natural habitat. Radio
      tracking was used to follow the fate of 60 released brown hares over a 4-year
      period, extending between November 2005 and November 2009. The survival rate
      among these animals after 12 months was estimated to be 37 %, with 22 tagged
      individuals surviving beyond 1 year post-release. The highest (40 %) level of
      mortality characterised the first month after release, while a second period of
      enhanced mortality coincided with the breeding season (altogether accounting for
      a 20 % mortality rate). There was no significant relationship between body mass
      and mortality rate in the first month following release. A natural cause of death
      was predation by mammals, which accounted for some 31 % of all losses. Remaining
      causes were poaching (13 %), hits by vehicles (7 %) and unidentified causes (9
      %). However, in at least 40 % of cases, it was not possible to determine the date
      when a released animal died, to say nothing of the cause of death.

PMID- 23002286
TI  - Seasonal and photoperiodic effects on lipid droplet size and lipid peroxidation
      in the brown adipose tissue of bank voles (Myodes glareolus).
AB  - Seasonal changes in lipid droplet size and lipid peroxidation in the brown
      adipose tissue (BAT) of wild bank voles were examined. In addition, a role of
      photoperiod in these changes was studied; bank voles were held from the birth
      under long photoperiod (LP) for 12 weeks, and then half of them was transferred
      to short photoperiod (SP) for 6 weeks and another one remained under LP. In the
      wild bank voles the absolute BAT weight was seasonally constant, while the
      significant differences in the lipid droplet size were observed. The smallest
      lipid droplets (mean, 11 MUm(2)) were seen in winter; they increased by 30 % in
      spring and reached the highest size (24 MUm(2)) in summer. Lipid peroxidation in
      the BAT did not differ significantly between the seasons, although high
      intraseason variation of this process was noted. The laboratory experiment
      revealed that the size of lipid droplets was determined by photoperiod; SP
      induced 13-fold decrease, and continuous exposure to LP brought about a further
      2.5-fold increase in the size of lipid droplets. Conversely, a significant
      decrease in lipid peroxidation was seen in LP bank voles in comparison with the
      SP animals. The data indicate that short photoperiod is responsible for the small
      size of lipid droplets in the BAT of bank voles during winter, which may be a
      necessary requirement for high thermogenic capacity of the tissue. Photoperiod
      appears also to affect lipid peroxidation in the BAT of these animals.

PMID- 23002288
TI  - Alternative strategies in the acquisition of home ranges by male pine martens in
      a high-density population.
AB  - Two strategies of home range acquisition by male subadult pine martens (Martes
      martes) were described from a high-density population inhabiting Bialowieza
      National Park. Four mother-offspring pairs were identified by genetic parentage
      assignments. Four subadult males showed two different strategies of home range
      acquisition: dispersal and sedentary. The dispersing males used an area 4-10
      times larger than in sedentary subadult males. A sedentary subadult male used his
      natal area with his mother, and in the following mating season, this male left
      this area and established a home range that overlapped greatly with another
      unrelated female near the natal range. A similar high overlap between another
      subadult male and an unrelated adult female persisted for 3 years. After the
      death of this female, the male extended his range to overlap slightly with two to
      four other females. The sedentary strategy adopted by some subadult males may
      explain the great variation in spacing patterns of solitary mammals.

PMID- 23002289
TI  - Metal-enhanced intrinsic fluorescence of nucleic acids using platinum
      nanostructured substrates.
AB  - We investigated the feasibility of using platinum nanostructures to accomplish
      the metal-enhanced fluorescence (MEF) in the UV spectral region. We examine the
      possibility for detection of the intrinsic fluorescence from nucleotides and G
      quadruplex DNA on platinum nanoparticles. Guanosine monophosphate (GMP) showed
      significant increases (~20-fold) in fluorescence intensities in the presence of
      platinum nanostructures when compared to quartz controls. G-quadruplex DNA
      demonstrated ~5-fold increase in fluorescence intensity and higher photostability
      in the presence of Pt nanostructures. We performed finite element method
      simulations to explore how Pt nanoparticles interact with plane waves and
      conformed that the Pt nanostructures are promising for enhancing the fluorescence
      emission in the UV region.

PMID- 23002290
TI  - Sexual modernity in the works of Richard von Krafft-Ebing and Albert Moll.
AB  - The modern notion of sexuality took shape at the end of the nineteenth century,
      especially in the works of Richard von Krafft-Ebing and Albert Moll. This
      modernisation of sexuality was closely linked to the recognition of sexual
      diversity, as it was articulated in the medical-psychiatric understanding of
      what, at that time, was labelled as perversion. From around 1870, psychiatrists
      shifted the focus from immoral acts, a temporary deviation of the norm, to an
      innate morbid condition. In the late nineteenth century, several psychiatrists,
      collecting and publishing more and more case histories, classified and explained
      the wide range of deviant sexual behaviours they traced. The emergence of medical
      sexology meant that perversions could be diagnosed and discussed. Against this
      background both Krafft-Ebing and Moll articulated a new perspective, not only on
      perversion, but also on sexuality in general. Krafft-Ebing initiated and Moll
      elaborated a shift from a psychiatric perspective in which deviant sexuality was
      explained as a derived, episodic and more or less singular symptom of a more
      fundamental mental disorder, to a consideration of perversion as an integral part
      of a more general, autonomous and continuous sexual instinct. Before Sigmund
      Freud and others had expressed similar views, it was primarily through the
      writings of Krafft-Ebing and Moll that a new understanding of human sexuality
      emerged.

PMID- 23002291
TI  - Loss of innocence: Albert Moll, Sigmund Freud and the invention of childhood
      sexuality around 1900.
AB  - This paper analyses how, prior to the work of Sigmund Freud, an understanding of
      infant and childhood sexuality emerged during the nineteenth century. Key
      contributors to the debate were Albert Moll, Max Dessoir and others, as fin-de
      siecle artists and writers celebrated a sexualised image of the child. By the
      beginning of the twentieth century, most paediatricians, sexologists,
      psychologists, psychiatrists, psychoanalysts and pedagogues agreed that sexuality
      formed part of a child's 'normal' development. This paper argues that the main
      disagreements in discourses about childhood sexuality related to different
      interpretations of children's sexual experiences. On the one hand stood an
      explanation that argued for a homology between children's and adults' sexual
      experiences, on the other hand was an understanding that suggested that adults
      and children had distinct and different experiences. Whereas the homological
      interpretation was favoured by the majority of commentators, including Moll,
      Freud, and to some extent also by C.G. Jung, the heterological interpretation was
      supported by a minority, including childhood psychologist Charlotte Buhler.

PMID- 23002292
TI  - The sexologist Albert Moll--between Sigmund Freud and Magnus Hirschfeld.
AB  - Albert Moll was one of the most influential sexologists during the first three
      decades of the twentieth century. In contrast to his rivals Sigmund Freud and
      Magnus Hirschfeld, his achievements have not yet been recognised adequately. The
      author gives a comparative account of the work of these three protagonists. This
      shows that Moll formed some ideas which are regarded as psychoanalytical today
      before Freud, and that he, in contrast to Hirschfeld, was able to reflect
      critically on contemporary discourses, such as the debates on racial improvement
      through eugenics. As scientific theories, Freud's psychoanalysis represented the
      unconscious, fantasy, experience and latency, while Moll's sexology represented
      consciousness, ontological reality, behaviour and manifestation. Moll's major
      disagreement with Hirschfeld's sexology was his advocacy of apolitical and
      impartial science, whereas Hirschfeld's aim was to achieve sexual reforms
      politically. Added to these differences were strong personal animosities. Freud
      called Moll a 'beast' and 'pettifogger'; and Moll complained about Hirschfeld's
      'problematic' character. When Hirschfeld escaped the Nazi terror and went to
      Paris, Moll denounced him in order to prevent him rebuilding a new existence in
      exile.

PMID- 23002293
TI  - Sexual science and sexual forensics in 1920s Germany: Albert Moll as (S)expert.
AB  - Using court records involving the expert testimony of the Berlin sexologist
      Albert Moll, my article demonstrates that during the early 1920s a shift in the
      'epistemologies of justice' concerning the adjudication of sex crimes took place
      within German courtrooms. Namely, presiding judges considered a greater number of
      sexual acts as punishable, despite no change in the laws themselves. Central to
      my argument is the role of expert testimony in practice and its critical
      reception. By focusing upon the rhetorical strategies presented by attorneys,
      judges and expert witnesses (as well as defendants themselves and their
      relatives), it illustrates the functions of expert and tacit knowledge in court,
      which were often not mutually exclusive. Moll's stature also enabled him to
      translate his scientific-medical expertise into state support for his
      testimonies, as well as the rebuilding of an international community of
      sexological authorities. It was only under Moll's leadership that the First
      International Sexology Congress could take place in 1926, an event that marked
      the apex of his prestige.

PMID- 23002294
TI  - 'God's ethicist': Albert Moll and his medical ethics in theory and practice.
AB  - In 1902, Albert Moll, who at that time ran a private practice for nervous
      diseases in Berlin, published his comprehensive book on medical ethics, Arztliche
      Ethik. Based on the concept of a contractual relationship between doctor and
      client, it gave more room to the self-determination of patients than the
      contemporary, usually rather paternalistic, works of this genre. In the first
      part of the present paper this is illustrated by examining Moll's views and
      advice on matters such as truthfulness towards patients, euthanasia, and
      abortion. The second part of this article discusses how Moll engaged with the
      then publicly debated issues of experimentation on hospital patients and the
      'trade' of foreign private patients between agents and medical consultants. In
      both matters Moll collected evidence of unethical practices and tried to use it
      to bring about change without damaging his or the profession's reputation.
      However, with his tactical manoeuvres, Moll made no friends for himself among his
      colleagues or the authorities; his book on ethics also met with a generally cool
      response from the medical profession and seems to have been more appreciated by
      lawyers than by other doctors.

PMID- 23002295
TI  - Sexological deliberation and social engineering: Albert Moll and the
      sterilisation debate in late imperial and Weimar Germany.
AB  - The physician and sexologist Albert Moll, from Berlin, was one of the main
      protagonists within the German discourse on the opportunities and dangers of
      social engineering, by eugenic interventions into human life in general, as well
      as into reproductive hygiene and healthcare policy in particular. One of the main
      sexological topics that were discussed intensively during the late-Wilhelminian
      German Reich and the Weimar Republic was the question of the legalisation of
      voluntary and compulsory sterilisations on the basis of medical, social, eugenic,
      economic or criminological indications. As is clear from Moll's conservative
      principles of medical ethics, and his conviction that the genetic knowledge
      required for eugenically indicated sterilisations was not yet sufficiently
      elaborated, he had doubts and worries about colleagues who were exceedingly
      zealous about these surgical sterilisations--especially Gustav Boeters from
      Saxony.

PMID- 23002296
TI  - Policing epistemic deviance: Albert Von Schrenck-Notzing and Albert Moll(1).
AB  - Shortly after the death of Albert von Schrenck-Notzing (1862-1929), the doyen of
      early twentieth century German para psychology, his former colleague in hypnotism
      and sexology Albert Moll (1862-1939) published a treatise on the psychology and
      pathology of parapsychologists, with Schrenck-Notzing serving as a prototype of a
      scientist suffering from an 'occult complex'. Moll's analysis concluded that
      parapsychologists vouching for the reality of supernormal phenomena, such as
      telepathy, clairvoyance, telekinesis and materialisations, suffered from a morbid
      will to believe, which paralysed their critical faculties and made them cover
      obvious mediumistic fraud. Using Moll's treatment of Schrenck-Notzing as an
      historical case study of boundary disputes in science and medicine, this essay
      traces the career of Schrenck-Notzing as a researcher in hypnotism, sexology and
      parapsychology; discusses the relationship between Moll and Schrenck-Notzing; and
      problematises the pathologisation and defamation strategies of deviant
      epistemologies by authors such as Moll.

PMID- 23002297
TI  - 'Trick', 'manipulation' and 'farce': Albert Moll's critique of occultism.
AB  - In July 1925, the psychiatrist Albert Moll appeared before the district court in
      Berlin-Schoneberg charged with having defamed the medium Maria Vollhardt (alias
      Rudloff) in his 1924 book Der Spiritismus [Spiritism]. Supported by some of
      Berlin's most prominent occultists, the plaintiff--the medium's husband--argued
      that Moll's use of terms such as 'trick', 'manipulation' and 'farce' in reference
      to Vollhardt's phenomena had been libellous. In the three-part trial that
      followed, however, Moll's putative affront to the medium--of which he was
      eventually acquitted--was overshadowed, on the one hand, by a debate over the
      scientific status of parapsychology, and on the other, by the question of who-
      parapsychologists, occultists, psychiatrists or jurists--was entitled to claim
      epistemic authority over the occult. This paper will use the Rudloff-Moll trial
      as a means of examining Moll's critique of occultism, not only as it stood in the
      mid-1920s, but also as it had developed since the 1880s. It will also provide
      insight into the views of Germany's occultists and parapsychologists, who argued
      that their legitimate bid for scientific credibility was hindered by Dunkelmanner
      [obscurantists] such as Albert Moll.

PMID- 23002298
TI  - Albert Moll sources and bibliography.

PMID- 23002301
TI  - Open access and an additional publishing option.

PMID- 23002302
TI  - Asepsis and bacteriology: a realignment of surgery and laboratory science.
AB  - This paper examines the origins of aseptic surgery in the German-speaking
      countries. It interprets asepsis as the outcome of a mutual realignment of
      surgery and laboratory science. In that process, phenomena of surgical reality
      were being modelled and simplified in the bacteriological laboratory so that they
      could be subjected to control by the researcher's hands and eyes. Once control
      was achieved, it was being extended to surgical practice by recreating the
      relevant features of the controlled laboratory environment in the surgical work
      place. This strategy can be seen in the adoption of Robert Koch's bacteriology by
      German-speaking surgeons, and the resulting technical changes of surgery, leading
      to a set of beliefs and practices, which eventually came to be called 'asepsis'.

PMID- 23002303
TI  - 'Looking as little like patients as persons well could': hypnotism, medicine and
      the problem of the suggestible subject in late nineteenth-century Britain.
AB  - During the late nineteenth century, many British physicians rigorously
      experimented with hypnosis as a therapeutic practice. Despite mounting evidence
      attesting to its wide-ranging therapeutic uses publicised in the 1880s and 1890s,
      medical hypnosis remained highly controversial. After a decade and a half of
      extensive medical discussion and debate surrounding the adoption of hypnosis by
      mainstream medical professionals--including a thorough inquiry organised by the
      British Medical Association--it was decisively excluded from serious medical
      consideration by 1900. This essay examines the complex question of why hypnosis
      was excluded from professional medical practice by the end of the nineteenth
      century. Objections to its medical adoption rarely took issue with its supposed
      effectiveness in producing genuine therapeutic and anaesthetic results. Instead,
      critics' objections were centred upon a host of social and moral concerns
      regarding the patient's state of suggestibility and weakened 'will-power' while
      under the physician's hypnotic 'spell'. The problematic question of precisely how
      far hypnotic 'rapport' and suggestibility might depart from the Victorian liberal
      ideal of rational individual autonomy lay at the heart of these concerns. As this
      essay demonstrates, the hypnotism debate was characterised by a tension between
      physicians' attempts to balance their commitment to restore patients to health
      and pervasive middle-class concerns about the rapid and ongoing changes
      transforming British society at the turn of the century.

PMID- 23002304
TI  - Re-visiting 'Galen in Tibet'.
AB  - This paper readdresses the assertion found in much secondary literature that
      Greek medicine was adopted in Tibet in the seventh and eighth centuries. I
      discuss some of the traces of Galenic medical knowledge in early Tibetan
      medicine, and raise the question of why Tibetan medical histories who mention
      Galen give Galenic medicine a much more significant place than is evidenced in
      the Tibetan medical literature itself. I discuss some historiographical
      considerations and argue that the centrality given to Galenic medicine is more
      indicative of the period in which these sources are written than of the period
      which they presumably describe.

PMID- 23002305
TI  - Who was he? Reflections on China's first medical 'naturalist'.
AB  - This paper examines the reasons why Physician He (Yi-He, sixth century BCE) was
      regarded as a founder in the classical medical tradition of China. By most
      accounts, Physician He's importance owes much to his theoretical innovations. In
      contrast to earlier healers, Physician He purportedly framed the aetiology of
      illnesses solely in terms of natural causes, as opposed to attributing sickness
      to gods or demons. In this paper, I reread a famous episode in the Commentary by
      Zuo, which is often cited as evidence of the physician's naturalism. By paying
      close attention to the formal elements of the narrative as well as its larger
      discursive context, I argue that the standard reading of Physician He falls
      short. The episode provides little evidence of any secular challenge to religious
      conceptions of illness, and Physician He was, in fact, patterned after occult
      experts. A careful look moreover at the reception of Physician He in premodern
      histories of medicine reveals that the physician was extolled for his attunement
      to the will of the spirits as well as his powers of examination. Physician He's
      reputation as a naturalist furthermore represents a modern interpretation, one
      that reflects efforts to defend the indigenous medical tradition against its
      biomedical detractors.

PMID- 23002308
TI  - Ethnic and Gender Variation in Religious Involvement: Patterns of Expression in
      Young Adulthood.
AB  - This study used latent class analysis to empirically derive profiles of religious
      involvement among a sample of 808 young adults and describe ethnic and gender
      differences within such religious involvement patterns. Items on the Duke
      Religion Index were included as part of a larger longitudinal survey of
      emotional, physical, and behavioral health. The scale measured the
      organizational, nonorganizational, and intrinsic dimensions of religiosity
      (Koenig et al. 2001) in a sample of young adults at two waves of the study-age 27
      and age 30. At age 27, five religious profiles were distinguishable in the sample
      while at age 30 six profiles emerged. Ethnic differences were found for each of
      the religious profiles where religious involvement manifested in different ways.
      Religious profiles between ages 27 and 30 changed over time and were affected by
      gender and ethnicity.

PMID- 23002309
TI  - Multi-component synthesis of 2-amino-6-(alkyllthio)pyridine-3,5-dicarbonitriles
      using Zn(II) and Cd(II) metal-organic frameworks (MOFs) under solvent-free
      conditions.
AB  - Multi-component synthesis 2-amino-3,5-dicarbonitrile-6-thio-pyridines has been
      developed by using the reaction of aldehydes, malononitrile, and thiophenols in
      the presence of a Zn (II) or a Cd(II) metal-organic framework (MOF) as the
      heterogeneous catalyst. This protocol tolerates different functional groups on
      the substrates and does not require the use of any organic solvent. Moreover, the
      Zn(II) and Cd (II) MOF catalysts can be recovered and reused for a number of runs
      without loss of activity.

PMID- 23002310
TI  - Advanced Oxidation Processes in Triton X-100 and Wash-up Liquid Removal from
      Wastewater Using Modified TiO(2)/Al(2)O(3) Photocatalysts.
AB  - Photocatalytic methods were applied to remove the recalcitrant or toxic
      pollutants from the water. The two models of wastewater containing either non
      ionic surfactant Triton X-100 or commercially available wash-up liquid were
      tested in a self-constructed band reactor during the laboratory studies. The
      photocatalyst, being typed TiO(2), was supported by porous Al(2)O(3) and modified
      by the addition of Cu, Fe, Zn, Ni, Mo or Co. The photocatalysts were
      characterised by N(2) adsorption-desorption, XRF, XRD, SEM-EDX, Raman and UV-Vis
      spectroscopy. All catalysts were efficient in the photocatalytic oxidation of
      surfactants, and they enabled at least 85 % COD reduction. TiO(2)/Al(2)O(3)
      photocatalysts modified by the transition metals were efficient only for more
      complicated compositions of surfactants. The effect of H(2)O(2) (0.01 vol.%)
      addition was also examined and compared with a type of compound and catalyst used
      in this case a positive effect for Triton X-100 was only observed over the
      photocatalyst modified by Ni. When it comes to the wash-up liquid photoremoval,
      all studied photocatalysts seem to be slightly influenced by H(2)O(2) addition.
      It was also observed that it is not economically justified to conduct such
      treatment for more than 2 h.

PMID- 23002311
TI  - Effects of Different Factors on Water Flow and Solute Transport Investigated by
      Time Domain Reflectometry in Sandy Clay Loam Field Soil.
AB  - Factors affecting preferential flow and transport in the vadose zone need to be
      investigated by experiments and simulations to protect groundwater against
      surface applied chemicals. The objectives of this study were to investigate the
      effects of several factors (soil structure, initial soil water content (SWC), and
      application rate) and their interactions on the extent of preferential flow and
      transport in a sandy clay loam field soil using the time domain reflectometry
      (TDR) for measuring SWC and electrical conductivity (EC) in 12 treatments,
      modeling (by HYDRUS-1D and VS2DTI) the measured SWC and EC, and conducting
      statistical tests for comparing the means of the measured and modeled SWC and EC
      and solute transport parameters (pore water velocity and dispersion coefficient)
      obtained by inversely fitting in the CXTFIT program. The study results showed
      that the applied solution moved faster in the undisturbed, wet initial SWC, and
      higher application rate experimental conditions than in the disturbed, dry
      initial SWC, and lower application rate, respectively, based on the analysis of
      the changes in TDR measured SWC and EC with depth at 1, 2, 5, and 15 h of the
      experiments. However, the effects of interactive factors or treatments on water
      flow and solute transport were not clear enough. The modeling results showed that
      HYDRUS-1D was better than VS2DTI in the estimation of EC and especially SWC, but
      overall the models had relatively low performances in the simulations.
      Statistical test results also showed that the treatments had different flow and
      transport characteristics because they were divided into different groups in
      terms of the means of SWC and EC and solute transport parameters. These results
      suggest that similar experiments with more distinct interactions and modeling
      studies with different approaches need to be considered for better understanding
      the complex flow and transport processes in the vadose zone.

PMID- 23002313
TI  - Decolourization of Diazo Evans Blue by Two Strains of Pseudomonas fluorescens
      Isolated from Different Wastewater Treatment Plants.
AB  - The use of azo dyes is popular in different branches of industry. Discharge of
      colourants to surface water cause harmful environmental effects. The aim of the
      present study was evaluation of effectiveness of diazo Evans blue decolourization
      by two Pseudomonas strains and estimation of process byproducts toxicity. In
      static conditions, both tested strains removed more than 85 % of dye after 48 h
      and completely decolorized samples after 120 h. Agitation had negative impact on
      Evans blue removal (less than 70 % of dye removed after 120 h). Ecotoxicological
      effects were different for both studied strains beside comparable decolourization
      effectiveness. Increase of zootoxicity was noticed for strain Sz6 and decrease
      from IV to III class was noticed for strain SDz3. Optimization of process
      conditions for the most promising strain SDz3 should be deeply examined.

PMID- 23002312
TI  - The Phytotoxicity Changes of Sewage Sludge-Amended Soils.
AB  - The aim of the present study was the estimation of changes in the phytotoxicity
      of soils amended with sewage sludge with relation to Lepidium sativum, Sinapis
      alba and Sorghum saccharatum. The study was realised in the system of a plot
      experiment for a period of 29 months. Samples for analyses were taken at the
      beginning of the experiment, and then after 5, 17 and 29 months. Two kinds of
      sewage sludge, with varying properties, were added to a sandy soil (soil S) or a
      loamy soil (soil L) at the dose of 90 t/ha. The addition of sewage sludge to the
      soils at the start of the experiment caused a significant reduction of both seed
      germination capacity and root length of the test plants, the toxic effect being
      distinctly related to the test plant species. With the passage of time the
      negative effect of sewage sludge weakened, the extent of its reduction depending
      both of the kind of sewage sludge applied and on the type of soil. Phytotoxicity
      of the soils amended with the sewage sludges was significantly lower at the end
      of the experiment than at the beginning. The species of the plants grown on the
      soils also had a significant effect on their phytotoxicity. The greatest
      reduction of toxicity was observed in the soil on which no plants were grown
      (sandy soil) and in the soil under a culture of willow (loamy soil). Solid phase
      of sewage sludge-amended soils was characterised by higher toxicity than their
      extracts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11270-012-1248-8) contains supplementary material, which is
      available to authorized users.

PMID- 23002314
TI  - The Influence of Cadmium Stress on the Content of Mineral Nutrients and Metal
      Binding Proteins in Arabidopsis halleri.
AB  - We investigated the influence of cadmium stress on zinc hyperaccumulation,
      mineral nutrient uptake, and the content of metal-binding proteins in Arabidopsis
      halleri. The experiments were carried out using plants subjected to long-term
      cadmium exposure (40 days) in the concentrations of 45 and 225 MUM Cd(2+).
      Inductively coupled plasma-mass spectrometry, size exclusion chromatography
      coupled with plasma-mass spectrometry, and laser ablation inductively coupled
      plasma-mass spectrometry used for ablation of polyacylamide gels were employed to
      assess the content of investigated elements in plants as well as to identify
      metal-binding proteins. We found that A. halleri is able to translocate cadmium
      to the aerial parts in high amounts (translocation index >1). We showed that Zn
      content in plants decreased significantly with the increase of cadmium content in
      the growth medium. Different positive and negative correlations between Cd
      content and mineral nutrients were evidenced by our study. We identified more
      than ten low-molecular-weight (<100 kDa) Cd-binding proteins in Cd-treated
      plants. These proteins are unlikely to be phytochelatins or metallothioneins. We
      hypothesize that low-molecular-weight Cd-binding proteins can be involved in
      cadmium resistance in A. halleri. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11270-012-1292-4) contains supplementary
      material, which is available to authorized users.

PMID- 23002315
TI  - Conditional and Marginal Estimates in Case-Control Family Data - Extensions and
      Sensitivity Analyses.
AB  - This work considers two specific estimation techniques for the family specific
      proportional hazards model and for the population-averaged proportional hazards
      model. So far, these two estimation procedures were presented and studied under
      the gamma frailty distribution mainly because of its simple interpretation and
      mathematical tractability. Modifications of both procedures for other frailty
      distributions, such as inverse Gaussian, positive stable and a specific case of
      discrete distribution, are presented. By extensive simulations, it is shown that
      under the family specific proportional hazards model, the gamma frailty model
      appears to be robust to frailty distribution misspecification in both bias and
      efficiency loss in the marginal parameters. The population-averaged proportional
      hazards model, is found to be robust under the gamma frailty model
      misspecification only under moderate or weak dependency within cluster members.

PMID- 23002316
TI  - Articulatory gestures are individually selected in production.
AB  - Most models of speech planning and production incorporate a selection mechanism,
      whereby units are activated in parallel and chosen for execution sequentially.
      The lowest level units which can be selected are assumed to be segments, i.e.
      consonants and vowels. The features or articulatory gestures affiliated with
      segments are presumed to be automatically selected as a consequence of segmental
      selection. An alternative possibility is that articulatory gestures themselves
      are subject to a selection process; this predicts that there can be circumstances
      in which gestures affiliated with the same segment fail to co-occur. We conducted
      a stop-signal task in which subjects produced /pa/- or /ka/-initial monosyllables
      and disyllables in response to a go-signal; on 50% of trials subjects halted
      production as quickly as possible when given a stop-signal within +/-300 ms of
      the go-signal. Articulatory kinematics were recorded using a speech magnetometer.
      We found that vowel-affiliated gestures of glottal adduction, tongue body
      lowering, and bilabial opening did not necessarily co-occur in the context of
      halting speech. This finding indicates that gestures are selected individually,
      rather than as an automatic consequence of segmental selection.

PMID- 23002317
TI  - Density and Viscosity of Binary Mixtures of Thiocyanate Ionic Liquids + Water as
      a Function of Temperature.
AB  - Densities and viscosities have been determined for binary mixtures of the ionic
      liquids (ILs) 1-butyl-3-methylimidazolium thiocyanate [BMIM][SCN], or 1-butyl-4
      methylpyridinium thiocyanate [BMPy][SCN], or 1-butyl-1-methylpyrrolidinium
      thiocyanate [BMPYR][SCN], or 1-butyl-1-methylpiperidinium thiocyanate
      [BMPIP][SCN] with water over wide range of temperatures (298.15-348.15) K and
      ambient pressure. The thermal properties of [BMPy][SCN], i.e. glass transition
      temperature and the heat capacity at glass transition, have been measured using a
      differential scanning microcalorimetry, DSC. The decomposition of [BMPy][SCN] was
      detected. The density and viscosity correlations for these systems have been made
      using an empirical second-order polynomial and by the Vogel-Fulcher-Tammann
      equation, respectively. The concentration dependences have been described by
      polynomials. The excess molar volumes and deviations in viscosity have been
      calculated from the experimental values and were correlated by Redlich-Kister
      polynomial expansions. The variations of these parameters, with compositions of
      the mixtures and temperature, have been discussed in terms of molecular
      interactions. A qualitative analysis of the trend of properties with composition
      and temperature was performed. Further, the excess partial molar volumes,
      [Formula: see text] and [Formula: see text], were calculated and discussed. The
      isobaric expansivities (coefficient of thermal expansion), alpha, and the excess
      isobaric expansivities, alpha(E), were determined for four ILs and their mixtures
      with water. The results indicate that the interactions of thiocyanate ILs with
      water is not as strong as with alcohols, which is shown by the positive/slightly
      negative excess molar volumes in these binary systems. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s10953-012-9875-7)
      contains supplementary material, which is available to authorized users.

PMID- 23002318
TI  - Spoken verb processing in Spanish: An analysis using a new online resource.
AB  - Verbs are one of the basic building blocks of grammar, yet few studies have
      examined the grammatical, morphological, and phonological factors contributing to
      lexical access and production of Spanish verb inflection. This report describes
      an online data set that incorporates psycholinguistic dimensions for 50 of the
      most common early-acquired Spanish verbs. Using this data set, predictors of
      response time (RT) from stimulus onset and mean differences at offset are
      examined. Native Spanish speakers, randomly assigned to one of two tasks,
      listened to prerecorded verbs and either repeated the verb (single word
      shadowing) or produced its corresponding pronoun. Factors such as stimulus
      duration, number of syllables, syllable stress position, and specific levels of
      initial phoneme facilitated both shadowing of a verb and production of its
      pronoun. Higher frequency verbs facilitated faster verb repetition, whereas verbs
      with alternative pronouns increased RT to pronoun production. Mean differences at
      offset (stimulus duration is removed) indicated that listeners begin speaking
      earlier when the verb is longer and multisyllabic compared to shorter,
      monosyllabic words. These results highlight the association between
      psycholinguistic factors and RT measures of verb processing, in particular,
      features unique to languages like Spanish, such as alternative pronoun and tense.

PMID- 23002319
TI  - Does Discourse Congruence Influence Spoken Language Comprehension before Lexical
      Association? Evidence from Event-Related Potentials.
AB  - The goal of this study was to examine how lexical association and discourse
      congruence affect the time course of processing incoming words in spoken
      discourse. In an ERP norming study, we presented prime-target pairs in the
      absence of a sentence context to obtain a baseline measure of lexical priming. We
      observed a typical N400 effect when participants heard critical associated and
      unassociated target words in word pairs. In a subsequent experiment, we presented
      the same word pairs in spoken discourse contexts. Target words were always
      consistent with the local sentence context, but were congruent or not with the
      global discourse (e.g., "Luckily Ben had picked up some salt and pepper/basil",
      preceded by a context in which Ben was preparing marinara sauce (congruent) or
      dealing with an icy walkway (incongruent). ERP effects of global discourse
      congruence preceded those of local lexical association, suggesting an early
      influence of the global discourse representation on lexical processing, even in
      locally congruent contexts. Furthermore, effects of lexical association occurred
      earlier in the congruent than incongruent condition. These results differ from
      those that have been obtained in studies of reading, suggesting that the effects
      may be unique to spoken word recognition.

PMID- 23002320
TI  - Molecular Characterization of A(1) and A(2a) Adenosine Receptors.
AB  - Detailed amino acid sequence analyses of A(1) and A(2a) adenosine receptors were
      assembled by analogy to other G-protein-coupled receptors and correlated with
      pharmacological observations. Sites for phosphorylation, palmitoylation, and
      sodium binding have been proposed. Striatal A(2a) receptors from human and other
      species were photoaffinity-labeled using the selective, radioiodinated agonist
      PAPA-APEC. Selective chemical affinity labels for A(1) and A(2a) receptors have
      been introduced. For example, an isothiocyanate, p-DITC-APEC (100 nM),
      irreversibly diminished the B(max) for [(3)H]CGS 21680 (2-[4-[(2-carboxyethyl)
      phenyl] ethylamino]-5'-N-ethylcarboxamidoadenosine) binding in rabbit striatal
      membranes by 71% (K(d) unaffected), suggesting a direct modification of the
      ligand binding site. Novel trifunctional affinity labels have been designed.
      Rabbit and human A(2a) receptors were characterized using [(3)H]XAC binding in
      the presence of 50 or 25 nM CPX (8-cyclopentyl-l,3-dipropylxanthine),
      respectively. The inhibition of A(2) radioligand binding by the histidyl
      modifying reagent diethylpyrocarbonate suggested the involvement of His residues
      in interactions with adenosine agonists and antagonists. Properties of
      transiently expressed mutants of bovine A(1) receptors in which either His(251)
      or His(278) residues have been substituted with Leu suggest that both histidines
      are important in binding.

PMID- 23002321
TI  - The Aryl Hydrocarbon Receptor Influences Transplant Outcomes in Response to
      Environmental Signals.
AB  - The aryl hydrocarbon receptor (AHR) is a cytosolic transcription factor with
      numerous endogenous and xenobiotic ligands, most notably 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Recent data suggests that TCDD may induce
      regulatory T cells, while a second AHR ligand, FICZ, promotes Th17
      differentiation. The aim was to examine whether injection of recipient mice with
      either TCDD or FICZ altered skin allograft rejection in a fully mismatched model.
      TCDD or FICZ was given to recipient C57BL/6 mice intraperitoneally (IP). Twenty
      four hr later, donor skin was grafted from BALB/c mice. An additional dose of
      FICZ was given on day 3. Treatment with TCDD delayed graft rejection for more
      than 4 weeks while FICZ treatment accelerated rejection by 1 - 2 days. In vivo
      exposure with TCDD led to a rise in the frequency of FoxP3(+) CD4(+) T cells in
      the spleen, while FICZ increased IL-17 secretion by splenocytes from treated
      animals. Activation of the AHR receptor by different AHR ligands in vivo resulted
      in opposing effects on skin graft survival. AHR serves as a sensor to
      environmental signals, with effects on the acquired immune system that may alter
      outcomes after organ transplantation. This model will be useful to further
      delineate direct effects of the environment on the immune system and outcomes of
      organ transplantation.

PMID- 23002322
TI  - A new on-line resource for psycholinguistic studies.
AB  - Picture naming is a widely used technique in psycholinguistic studies. Here, we
      describe new on-line resources that our project has compiled and made available
      to researchers on the world wide web at http://crl.ucsd.edu/~aszekely/ipnp/. The
      website provides access to a wide range of picture stimuli and related norms in
      seven languages. Picture naming norms, including indices of name agreement and
      latency, for 520 black-and-white drawings of common objects and 275 concrete
      transitive and intransitive actions are presented. Norms for age-of-acquisition,
      word-frequency, familiarity, goodness-of-depiction, and visual complexity are
      included. An on-line database query system can be used to select a specific range
      of stimuli, based on parameters of interest for a wide range of studies on
      healthy and clinical populations, as well as studies of language development.

PMID- 23002323
TI  - Coping with stress, coping with violence: Links to mental health outcomes among
      at-risk youth.
AB  - Coping reactions to stressful events are important links between difficult
      experiences and the emergence of psychopathology. In this study we compared
      youths' negative coping with stress in general to their negative coping with
      violence in particular, and utilized a person-centered analytic approach to
      examine how patterns of coping relate to various mental health outcomes. We
      utilized survey interview measures to collect data from a sample of 131 youth
      (ages 11-14, 100% ethnic minority) residing in an economically distressed
      metropolitan area of the northeast. We observed significant relations between
      youths' tendencies to cope with stress and violence via externalized-internalized
      strategies (e.g., yelling to let off steam, crying) and their mental health
      symptoms. However, we generally did not observe relations between engagement in
      distancing coping strategies (e.g., making believe nothing happened) and any
      problematic outcomes. Negative coping does not appear be a monolithic construct
      uniformly associated with negative outcomes for youth. Distancing coping might
      represent an especially useful short-term coping response for youth living in
      socioeconomically distressed conditions from the standpoint of inhibiting symptom
      development.

PMID- 23002324
TI  - The Association between Preschool Children's Social Functioning and Their
      Emergent Academic Skills.
AB  - This study examined the relationship between social functioning and emergent
      academic development in a sample of 467 preschool children (M = 55.9 months old,
      SD = 3.8). Teachers reported on children's aggression, attention problems, and
      prosocial skills. Preliteracy, language, and early mathematics skills were
      assessed with standardized tests. Better social functioning was associated with
      stronger academic development. Attention problems were related to poorer academic
      development controlling for aggression and social skills, pointing to the
      importance of attention in these relations. Children's social skills were related
      to academic development controlling for attention and aggression problems,
      consistent with models suggesting that children's social strengths and
      difficulties are independently related to their academic development. Support was
      not found for the hypothesis that these relationships would be stronger in boys
      than in girls. Some relationships were stronger in African American than
      Caucasian children. Children's self-reported feelings about school moderated
      several relationships, consistent with the idea that positive feelings about
      school may be a protective factor against co-occurring academic and social
      problems.

PMID- 23002325
TI  - Composition-structure relationships in the Li-ion battery electrode material
      LiNi(0.5)Mn(1.5)O(4).
AB  - A study of the correlations between the stoichiometry, secondary phases and
      transition metal ordering of LiNi(0.5)Mn(1.5)O(4) was undertaken by
      characterizing samples synthesized at different temperatures. Insight into the
      composition of the samples was obtained by electron microscopy, neutron
      diffraction and X-ray absorption spectroscopy. In turn, analysis of cationic
      ordering was performed by combining neutron diffraction with Li MAS NMR
      spectroscopy. Under the conditions chosen for the synthesis, all samples
      systematically showed an excess of Mn, which was compensated by the formation of
      a secondary rock salt phase and not via the creation of oxygen vacancies. Local
      deviations from the ideal 3:1 Mn:Ni ordering were found, even for samples that
      show the superlattice ordering by diffraction, with different disordered schemes
      also being possible. The magnetic behavior of the samples was correlated with the
      deviations from this ideal ordering arrangement. The in-depth crystal-chemical
      knowledge generated was employed to evaluate the influence of these parameters on
      the electrochemical behavior of the materials.

PMID- 23002326
TI  - Protective function of silicon deposition in Saccharina japonica sporophytes
      (Phaeophyceae).
AB  - We investigated biogenic silica deposition in sporophytes of kelp, Saccharina
      japonica (Laminariaceae). Silicon content was measured in different sporophyte
      regions and there was a trend for the silicon content to increase longitudinally
      from the stipe-blade transition to apical regions. The transverse trend was for
      the content to be higher in the marginal region than in the medial region. The
      silicon content was also higher in the scar and sorus regions compared with the
      adjacent vegetative regions. High silicon content was detected in the margin of
      the disc and in the sorus region of cultured sporophyte discs. Moreover,
      rhodamine 123 staining suggested that silicon was deposited in the mouth of the
      marginal wound of the disc. Rhodamine 123 fluorescence was also detected in the
      paraphyses and mucilaginous caps of sori. These results suggest that silicon
      plays important roles in tissue protection and vegetative tissue wound healing.
      It is also suggested that silicon is required for the protection of reproductive
      tissues. We also discuss the physiological and ecological roles of biogenic
      silica deposition in kelp and its management in cultivated fields.

PMID- 23002327
TI  - Improving word reading speed: individual differences interact with a training
      focus on successes or failures.
AB  - The effect of two training procedures on the development of reading speed in poor
      readers is examined. One training concentrates on the words the children read
      correctly (successes), the other on the words they read incorrectly (failures).
      Children were either informed or not informed about the training focus. A
      randomized controlled trial was conducted with 79 poor readers. They repeatedly
      read regularly spelled Dutch consonant-vowel-consonant words, some children their
      successes, others their failures. The training used a computerized flashcards
      format. The exposure duration of the words was varied to maintain an accuracy
      rate at a constant level. Reading speed improved and transferred to untrained,
      orthographically more complex words. These transfer effects were characterized by
      an Aptitude-Treatment Interaction. Poor readers with a low initial reading level
      improved most in the training focused on successes. For poor readers with a high
      initial reading level, however, it appeared to be more profitable to practice
      with their failures. Informing students about the focus of the training
      positively affected training: The exposure duration needed for children informed
      about the focus of the training decreased more than for children who were not
      informed. This study suggests that neither of the two interventions is superior
      to the other in general. Rather, the improvement of general reading speed in a
      transparent orthography is closely related to both the children's initial reading
      level and the type of words they practice with: common and familiar words when
      training their successes and uncommon and less familiar words with training their
      failures.

PMID- 23002328
TI  - Veritas(r) bovine pericardium for immediate breast reconstruction: a xenograft
      alternative to acellular dermal matrix products.
AB  - BACKGROUND: The technical advantages in utilizing human acellular dermal matrix
      (ADM) products as pectoral extenders in immediate breast reconstruction with
      tissue expanders or implants are well documented in the medical literature. In
      this study, the authors examine a commonly used biologic xenograft product that
      has not yet been described in the medical literature for use in immediate breast
      reconstruction to determine whether a lower overall complication rate is
      identified compared to published data on ADM products.  METHODS: A retrospective
      multicenter medical record review of data on 54 subjects in 93 tissue
      expander/implant-based, consecutive, immediate breast reconstructions from three
      surgeons at different institutions was performed in which Veritas(r) bovine
      pericardium was used as the biologic graft material for the pectoral extender. 
      RESULTS: Over a 24-month period with an average of 11-month follow-up,
      complication rates using Veritas(r) in breast reconstruction for seroma formation
      (7.5 %), marginal skin flap necrosis (5.4 %) infection (6.5 %), and capsular
      contracture (0 %) were found to compare equally or favorably with statistically
      significant lower overall complications relative to one comparison study and
      lower rates of marginal skin flap necrosis relative to two comparison studies
      based upon previously published data from multisurgeon studies using ADM
      products.  CONCLUSIONS: Overall complications were found to be lower with
      Veritas(r) than ADM products in comparable multisurgeon studies, though this was
      found to be statistically significant in only one comparison study. Level of
      Evidence: Level II, theraputic study.

PMID- 23002329
TI  - Age variation and sexual dimorphism in the sixteen diagnostic clusters of risk
      factors for the metabolic syndrome.
AB  - OBJECTIVE: To document age- and sex-related differences in the 16 phenotypes of
      risk factors for the metabolic syndrome (MS) among adults in the Fels
      Longitudinal Study (FLS).  METHODS: Data on risk factors for the MS were analyzed
      in 471 white men and 503 white women in the FLS. We used the Cochran-Armitage
      test to compare age- and sex-related differences in the prevalence of the 16
      diagnostic clusters of positive risk factors.  RESULTS: Of the 974 subjects, 238
      were found to meet diagnostic criteria for 15 of a possible 16 phenotypes of the
      MS. The prevalence of the MS was four times greater in subjects older than 40
      years than in subjects 20-40 years old. Older subjects had more risk factors
      exceeding criterion values than younger subjects. Among those who met three-to
      five criteria for the MS, younger subjects were more likely to have dyslipidemia,
      less likely to have high blood pressure (HBP), and two times less likely to have
      impaired fasting plasma glucose (IFG) than subjects 40+ years old. Older men were
      more likely than older women to have HBP and IFG. . We found that if one of the
      five risk factors reaches a criterion value, the values for the other four risk
      factors move closer to their own diagnostic criterion values in apparent
      synchrony.  CONCLUSIONS: Subjects 40+ years old are four times likelier to have
      the MS than younger subjects, and older men are at higher risk than older women.
      The mean values for each of the five risk factors get progressively worse as the
      number of risk factors meeting diagnostic criteria increases. Therefore, when one
      factor is found to meet its diagnostic criterion, levels of the other four risk
      factors should be measured. The different phenotypic patterns that comprise the
      MS should prompt clinicians to target specific risk factors for prevention or
      treatment. Certain phenotypes were found more commonly in women and certain
      others more commonly in men. Similarly, certain phenotypes were found more
      commonly in older than in younger age groups. These age- and sex-specific
      phenotypes should help clinicians to identify subjects at highest risk for
      certain risk factors and to initiate specifically tailored preventive and
      therapeutic interventions. Our observations should also stimulate clinical
      investigators and epidemiologists to ascertain what factors determine the sex and
      age specificity of certain phenotypes of the MS.

PMID- 23002330
TI  - Biocompatible, pH-sensitive AB(2) Miktoarm Polymer-Based Polymersomes:
      Preparation, Characterization, and Acidic pH-Activated Nanostructural
      Transformation.
AB  - Motivated by the limitations of liposomal drug delivery systems, we designed a
      novel histidine-based AB(2)-miktoarm polymer (mPEG-b-(polyHis)(2)) equipped with
      a phospholipid-mimic structure, low cytotoxicity, and pH-sensitivity. Using "core
      first" click chemistry and ring-opening polymerization, mPEG(2kDa)-b
      (polyHis(29kDa))(2) was successfully synthesized with a narrow molecular weight
      distribution (1.14). In borate buffer (pH 9), the miktoarm polymer self-assembled
      to form a nano-sized polymersome with a hydrodynamic radius of 70.2 nm and a very
      narrow size polydispersity (0.05). At 4.2 umol/mg polymer, mPEG(2kDa)-b
      (polyHis(29kDa))(2) strongly buffered against acidification in the endolysosomal
      pH range and exhibited low cytotoxicity on a 5 d exposure. Below pH 7.4 the
      polymersome transitioned to cylindrical micelles, spherical micelles, and finally
      unimers as the pH was decreased. The pH-induced structural transition of
      mPEG(2kDa)-b-(polyHis(29kDa))(2) nanostructures may be caused by the increasing
      hydrophilic weight fraction of mPEG(2kDa)-b-(polyHis(29kDa))(2) and can help to
      disrupt the endosomal membrane through proton buffering and membrane fusion of
      mPEG(2kDa)-b-(polyHis(29kDa))(2). In addition, a hydrophilic model dye, 5(6)
      carboxyfluorescein encapsulated into the aqueous lumen of the polymersome showed
      a slow, sustained release at pH 7.4 but greatly accelerated release below pH 6.8,
      indicating a desirable pH sensitivity of the system in the range of endosomal pH.
      Therefore, this polymersome that is based on a biocompatible histidine-based
      miktoarm polymer and undergoes acid-induced transformations could serve as a drug
      delivery vehicle for chemical and biological drugs.

PMID- 23002331
TI  - MicroRNAs in inflammatory bowel disease--pathogenesis, diagnostics and
      therapeutics.
AB  - The pathogenesis of inflammatory bowel disease (IBD) is complex and largely
      unknown. Until recently, research has focused on the study of protein regulators
      in inflammation to reveal the cellular and molecular networks in the pathogenesis
      of IBD. However, in the last few years, new and promising insights have been
      generated from studies describing an association between an altered expression of
      a specific class of non-coding RNAs, called microRNAs (miRs or miRNAs) and IBD.
      The short (approximately 22 nucleotides), endogenous, single-stranded RNAs are
      evolutionary conserved in animals and plants, and regulate specific target mRNAs
      at the post-transcriptional level. MiRNAs are involved in several biological
      processes, including development, cell differentiation, proliferation and
      apoptosis. Furthermore, it is estimated that miRNAs may be responsible for
      regulating the expression of nearly one-third of the genes in the human genome.
      Thus, miRNA deregulation often results in an impaired cellular function, and a
      disturbance of downstream gene regulation and signaling cascades, suggesting
      their implication in disease etiology. Despite the identification of more than
      1900 mature human miRNAs, very little is known about their biological functions
      and functional targets. Recent studies have identified dysregulated miRNAs in
      tissue samples of IBD patients and have demonstrated similar differences in
      circulating miRNAs in the serum of IBD patients. Thus, there is great promise
      that miRNAs will aid in the early diagnosis of IBD, and in the development of
      personalized therapies. Here, we provide a short review of the current state-of
      the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics.

PMID- 23002332
TI  - Post-endoscopic retrograde cholangio-pancreatography pancreatitis: is time for a
      new preventive approach?
AB  - Acute pancreatitis is the most common serious complication of endoscopic
      retrograde cholangio-pancreatography (ERCP) and its incidence may exceed 25% in
      some high-risk patient subsets. In some patients, pancreatitis may follow a
      severe course with pancreatic necrosis, multiorgan failure, permanent disability
      and even death. Hence, approaches which minimize both the incidence and severity
      of post-ERCP pancreatitis are worth pursuing. Pancreatic stents have been used
      with some success in the prevention of post-ERCP, while so far pharmacological
      trials have yielded disappointing results. A recent multicenter, randomized,
      placebo-controlled, double-blind trial has shown that rectally administered
      indomethacin is effective in reducing the incidence of post-ERCP pancreatitis,
      the occurrence of episodes of moderate-to-severe pancreatitis and the length of
      hospital stay in high-risk patients. These results together with the
      demonstration that rectal administration of indomethacin is not associated with
      enhanced risk of bleeding strongly support the use of this drug in the
      prophylaxis of post-ERCP pancreatitis.

PMID- 23002333
TI  - Mirizzi syndrome: history, current knowledge and proposal of a simplified
      classification.
AB  - Chronic complications of symptomatic gallstone disease, such as Mirizzi syndrome,
      are rare in Western developed countries with an incidence of less than 1% a year.
      The importance and implications of this condition are related to their associated
      and potentially serious surgical complications such as bile duct injury, and to
      its modern management when encountered during laparoscopic cholecystectomy. The
      pathophysiological process leading to the subtypes of Mirizzi syndrome has been
      explained by means of a pressure ulcer caused by an impacted gallstone at the
      gallbladder infundibulum, leading to an inflammatory response causing first
      external obstruction of the bile duct, and eventually eroding into the bile duct
      and evolving to a cholecystocholedochal or cholecystohepatic fistula. This
      article reviews the life of Pablo Luis Mirizzi, describes the earlier and later
      descriptions of Mirizzi syndrome, discusses the pathophysiological process
      leading to the development of these uncommon fistulas, reviews the current
      diagnostic modalities and surgical approaches and finally proposes a simplified
      classification for Mirizzi syndrome intended to standardize the reports on this
      condition and to eventually develop a consensual surgical approach to this
      unexpected and seriously dangerous condition.

PMID- 23002334
TI  - Interactions between hepatic iron and lipid metabolism with possible relevance to
      steatohepatitis.
AB  - The liver is an important site for iron and lipid metabolism and the main site
      for the interactions between these two metabolic pathways. Although conflicting
      results have been obtained, most studies support the hypothesis that iron plays a
      role in hepatic lipogenesis. Iron is an integral part of some enzymes and
      transporters involved in lipid metabolism and, as such, may exert a direct effect
      on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid
      secretion. On the other hand, iron in its ferrous form may indirectly affect
      lipid metabolism through its ability to induce oxidative stress and inflammation,
      a hypothesis which is currently the focus of much research in the field of non
      alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). The
      present review will first discuss how iron might directly interact with the
      metabolism of hepatic lipids and then consider a new perspective on the way in
      which iron may have a role in the two hit hypothesis for the progression of NAFLD
      via ferroportin and the iron regulatory molecule hepcidin. The review concludes
      that iron has important interactions with lipid metabolism in the liver that can
      impact on the development of NAFLD/NASH. More defined studies are required to
      improve our understanding of these effects.

PMID- 23002336
TI  - Hepatitis B in pregnancy.
AB  - Chronic hepatitis B virus (HBV) infection affects about 350 million individuals
      worldwide. Management of HBV infection in pregnancy is difficult because of
      several peculiar and somewhat controversial aspects. The aim of the present
      review is to provide a tool that may help physicians to correctly manage HBV
      infection in pregnancy. This review focuses on (1) the effect of pregnancy on HBV
      infection and of HBV infection on pregnancy; (2) the potential viral transmission
      from mother to newborn despite at-birth prophylaxis with immunoglobulin and
      vaccine; (3) possible prevention of mother-to-child transmission through
      antiviral drugs, the type of antiviral drug to use considering their efficacy and
      potential teratogenic effect, and the timing of their administration and
      discontinuation; and (4) the evidence for the use of elective caesarean section
      vs vaginal delivery and the possibility of breastfeeding.

PMID- 23002335
TI  - Diagnostic endoscopic ultrasonography: assessment of safety and prevention of
      complications.
AB  - Endoscopic ultrasonography (EUS) has gained wide acceptance as an important,
      minimally invasive diagnostic tool in gastroenterology, pulmonology, visceral
      surgery and oncology. This review focuses on data regarding risks and
      complications of non-interventional diagnostic EUS and EUS-guided fine-needle
      biopsy (EUS-FNB). Measures to improve the safety of EUS und EUS-FNB will be
      discussed. Due to the specific mechanical properties of echoendoscopes in EUS,
      there is a low but noteworthy risk of perforation. To minimize this risk,
      endoscopists should be familiar with the specific features of their equipment and
      their patients' specific anatomical situations (e.g., tumor stenosis,
      diverticula). Most diagnostic EUS complications occur during EUS-FNB. Pain, acute
      pancreatitis, infection and bleeding are the primary adverse effects, occurring
      in 1% to 2% of patients. Only a few cases of needle tract seeding and peritoneal
      dissemination have been reported. The mortality associated with EUS and EUS-FNB
      is 0.02%. The risks associated with EUS-FNB are affected by endoscopist
      experience and target lesion. EUS-FNB of cystic lesions is associated with an
      increased risk of infection and hemorrhage. Peri-interventional antibiotics are
      recommended to prevent cyst infection. Adequate education and training, as well
      consideration of contraindications, are essential to minimize the risks of EUS
      and EUS-FNB. Restricting EUS-FNB only to patients in whom the cytopathological
      results may be expected to change the course of management is the best way of
      reducing the number of complications.

PMID- 23002337
TI  - Gastro protective properties of the novel prostone SPI-8811 against acid-injured
      porcine mucosa.
AB  - AIM: To evaluate the protective properties of novel prostone ClC-2 agonist SPI
      8811 in porcine model of gastric acid injury. METHODS: Porcine gastric mucosa was
      mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl
      Ringer's solution (pH = 1.5) with or without SP1-8811 (1 MUmol/L), cystic
      fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172, 10
      MUmol/L, apical) and ClC-2 inhibitor ZnCl2, 300 MUmol/L, apical), on the apical
      surface of tissues. Transepithelial resistance and mucosal-to-serosal 3H-mannitol
      fluxes were measured over a 90-min period. Tissues were analyzed by morph metric
      techniques, Immunofluorescence and by western blots. RESULTS: Compared with
      control tissues, acid exposure decreased transepithelial electrical resistance
      (TER) and increased 3H-mannitol flux. Pretreatment of gastric mucosa with SPI
      8811 was protective against acid-induced decreases in TER (TER, 50 Omega.cm2 vs
      100 Omega.cm2) and abolished increases in flux (3H-mannitol flux, 0.10
      MUmol/L.cm2 vs 0.04 MUmol/L.cm2). Evidence of histological damage in the presence
      of acid was markedly attenuated by SPI-0811. Immunofluorescence and western
      analysis for occludin revealed enhanced localization to the region of the tight
      junction (TJ) after treatment with SPI-8811. Pretreatment with the ClC-2
      inhibitor ZnCl2, but not the selective CFTR inhibitor 172, attenuated SPI-8811
      mediated mucosal protection, suggesting a role for ClC-2. Prostone may serve both
      protective and reparative roles in injured tissues. CONCLUSION: ClC-2 agonist SPI
      8811 stimulated enhancement of mucosal barrier function by protecting TJ protein
      occludin in porcine gastric mucosa and thus protected the gastric acid injury in
      porcine stomach.

PMID- 23002338
TI  - Expression of the P2X2 receptor in different classes of ileum myenteric neurons
      in the female obese ob/ob mouse.
AB  - AIM: To examine whether the ob/ob mouse model of obesity is accompanied by
      enteric nervous system abnormalities such as altered motility. METHODS: The study
      examined the distribution of the P2X2 receptor (P2X2R) in myenteric neurons of
      female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co
      expression of the P2X2R with neuronal nitric oxide synthase (nNOS), choline
      acetyltransferase (ChAT), and calretinin (CalR) in neurons of the small intestine
      myenteric plexus in ob/ob and control female mice. In these sections, we used
      scanning confocal microscopy to analyze the co-localization of these markers as
      well as the neuronal density (cm2) and area profile (MUm2) of P2X2R-positive
      neurons. In addition, enteric neurons were labeled using the nicotinamide adenine
      dinucleotide (NADH) diaphorase method and analyzed with light microscopy as an
      alternate means by which to analyze neuronal density and area. RESULTS: In the
      present study, we observed a 29.6% increase in the body weight of the ob/ob
      animals (OG) compared to the control group (CG). In addition, the average small
      intestine area was increased by approximately 29.6% in the OG compared to the CG.
      Immunoreactivity (IR) for the P2X2R, nNOS, ChAT and CalR was detectable in the
      myenteric plexus, as well as in the smooth muscle, in both groups. This IR
      appeared to be mainly cytoplasmic and was also associated with the cell membrane
      of the myenteric plexus neurons, where it outlined the neuronal cell bodies and
      their processes. P2X2R-IR was observed to co-localize 100% with that for nNOS,
      ChAT and CalR in neurons of both groups. In the ob/ob group, however, we observed
      that the neuronal density (neuron/cm2) of P2X2R-IR cells was increased by 62%
      compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and
      57%, respectively, compared to control mice. The neuronal density of CalR-IR
      neurons was not different between the groups. Morphometric studies further
      demonstrated that the cell body profile area (MUm2) of nNOS-IR, ChAT-IR and CalR
      IR neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to
      controls. Staining for NADH diaphorase activity is widely used to detect
      alterations in the enteric nervous system; however, our qualitative examination
      of NADH-diaphorase positive neurons in the myenteric ganglia revealed an overall
      similarity between the two groups. CONCLUSION: We demonstrate increases in P2X2R
      expression and alterations in nNOS, ChAT and CalR IR in ileal myenteric neurons
      of female ob/ob mice compared to wild-type controls.

PMID- 23002339
TI  - Emerging roles of the ribonucleotide reductase M2 in colorectal cancer and
      ultraviolet-induced DNA damage repair.
AB  - AIM: To investigate the roles of the ribonucleotide reductase M2 (RRM2) subunit
      in colorectal cancer (CRC) and ultraviolet (UV)-induced DNA damage repair.
      METHODS: Immunohistochemical staining of tissue microarray was performed to
      detect the expression of RRM2. Seven CRC cell lines were cultured and three human
      colon cancer cell lines, i.e., HCT116, SW480 and SW620, were used. Reverse
      transcription polymerase chain reaction and Western blotting were performed to
      determine the mRNA and protein expression levels of RRM2, respectively. Cell
      proliferation assay, cell cycle analysis were performed. Cell apoptosis was
      evaluated by double staining with fluorescein isothiocyanate-conjugated Annexin V
      and propidium iodide (PI) using Annexin V/PI apoptosis kit. The motility and
      invasion of CRC cells were assessed by the Transwell chamber assay. Cells were
      irradiated with a 254 nm UV-C lamp to detect the UV sensitivity after RRM2
      depletion. RESULTS: Immunohistochemical staining revealed elevated RRM2 levels in
      CRC tissues. RRM2 overexpression was positively correlated with invasion depth (P
      < 0.05), poorly differentiated type (P = 0.0051), and tumor node metastasis stage
      (P = 0.0015). The expression of RRM2 in HCT116 cells was downregulated after
      transfection, and HCT116 cell proliferation was obviously suppressed compared to
      control groups (P < 0.05). In the invasion test, the number of cells that passed
      through the chambers in the RRM2-siRNA group was 81 +/- 3, which was lower than
      that in the negative control (289 +/- 7) and blank control groups (301 +/- 7.2).
      These differences were statistically significant (P < 0.01). Our data suggest
      that RRM2 overexpression may be associated with CRC progression. RRM2 silencing
      by siRNA may inhibit the hyperplasia and invasiveness of CRC cells, suggesting
      that RRM2 may play an important role in the infiltration and metastasis of CRC,
      which is a potential therapeutic strategy in CRC. In addition, RRM2 depletion
      increased UV sensitivity. CONCLUSION: These findings suggest that RRM2 may be a
      facilitating factor in colorectal tumorigenesis and UV-induced DNA damage repair.

PMID- 23002340
TI  - Perforated midgut diverticulitis: revisited.
AB  - AIM: To study and provide data on the evolution of medical procedures and
      outcomes of patients suffering from perforated midgut diverticulitis. METHODS:
      Three data sources were used: the Medline and Google search engines were searched
      for case reports on one or more patients treated for perforated midgut
      diverticulitis (Meckel's diverticulitis excluded) that were published after 1995.
      The inclusion criterion was sufficient individual patient data in the article.
      Both indexed and non-indexed journals were used. Patients treated for perforated
      midgut diverticulitis at Vestfold Hospital were included in this group. Data on
      symptoms, laboratory and radiology results, treatment modalities, surgical
      access, procedures, complications and outcomes were collected. The Norwegian
      patient registry was searched to find patients operated upon for midgut
      diverticulitis from 1999 to 2007. The data collected were age, sex, mode of
      access, surgical procedure performed and number of patients per year. Historical
      controls were retrieved from an article published in 1995 containing pertinent
      individual patient data. Statistical analysis was done with SPSS software.
      RESULTS: Group I: 106 patients (48 men) were found. Mean age was 72.2 +/- 13.1
      years (mean +/- SD). Age or sex had no impact on outcomes (P = 0.057 and P =
      0.771, respectively). Preoperative assessment was plain radiography in 53.3% or
      computed tomography (CT) in 76.1%. Correct diagnosis was made in 77.1% with CT,
      5.6% without (P = 0.001). Duration of symptoms before hospitalization was 3.6 d
      (range: 1-35 d), but longer duration was not associated with poor outcome (P =
      0.748). Eighty-six point eight percent of patients underwent surgery, 92.4% of
      these through open access where 90.1% had bowel resection. Complications occurred
      in 19.2% of patients and 16.3% underwent reoperation. Distance from perforation
      to Treitz ligament was 41.7 +/- 28.1 cm. At surgery, no peritonitis was found in
      29.7% of patients, local peritonitis in 47.5%, and diffuse peritonitis in 22.8%.
      Peritonitis grade correlated with the reoperation rate (r = 0.43). Conservatively
      treated patients had similar hospital length of stay as operated patients (10.6
      +/- 8.3 d vs 10.7 +/- 7.9 d, respectively). Age correlated with hospital stay (r
      = 0.46). No difference in outcomes for operated or nonoperated patients was found
      (P = 0.814). Group II: 113 patients (57 men). Mean age 67.6 +/- 16.4 years
      (range: 21-96 years). Mean age for men was 61.3 +/- 16.2 years, and 74.7 +/- 12.5
      years for women (P = 0.001). Number of procedures per year was 11.2 +/- 0.9, and
      bowel resection was performed in 82.3% of patients. Group III: 47 patients (21
      men). Patient age was 65.4 +/- 14.4 years. Mean age for men was 61.5 +/- 17.3
      years and 65.3 +/- 14.4 years for women. Duration of symptoms before
      hospitalization was 6.9 d (range: 1-180 d). No patients had a preoperative
      diagnosis, 97.9% of patients underwent surgery, and 78.3% had multiple
      diverticula. Bowel resection was performed in 67.4% of patients, and suture
      closure in 32.6%. Mortality was 23.4%. There was no difference in length of
      history or its impact on survival between Groups I and III (P = 0.241 and P =
      0.198, respectively). Resection was more often performed in Group I (P = 0.01).
      Mortality was higher in Group III (P = 0.002). CONCLUSION: In cases with
      contained perforation, conservative treatment gives satisfactory results,
      laparoscopy with lavage and drainage can be attempted and continued with a
      conservative course.

PMID- 23002341
TI  - Primary biliary cirrhosis-specific autoantibodies in first degree relatives of
      Greek primary biliary cirrhosis patients.
AB  - AIM: To determine the prevalence and significance of primary biliary cirrhosis
      (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC
      patients. METHODS: The presence of antimitochondrial antibodies (AMA) and PBC
      specific antinuclear antibodies (ANA) were determined using indirect
      immunofluorescence assays, dot-blot assays, and molecularly based enzyme-linked
      immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44
      PBC patients. In order to specify our results, the same investigation was
      performed in 40 healthy controls and in a disease control group consisting of 40
      asymptomatic for liver-related symptoms FDRs of patients with other autoimmune
      liver diseases namely, autoimmune hepatitis-1 or primary sclerosing cholangitis
      (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal
      liver function tests) FDRs of PBC patients and none of the healthy controls. The
      prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH
      1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI): 12%-28.1%
      vs 2.5%, 95% CI: 0.1%-14.7%, P = 0.01; 18.8%, 95% CI: 12%-28.1% vs 0%, 95% CI: 0%
      10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only
      one FDR from a PSC patient. Multivariate analysis showed that having a proband
      with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:
      1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk
      factors, a positive past history for urinary tract infections (UTI) was also
      independently associated with AMA detection in FDRs of PBC patients (odds ratio:
      3.92, 95% CI: 1.25-12.35, P = 0.02). CONCLUSION: In FDRs of Greek PBC patients,
      AMA prevalence is significantly increased and independently associated with past
      UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.

PMID- 23002343
TI  - "Extended" radical cholecystectomy for gallbladder cancer: long-term outcomes,
      indications and limitations.
AB  - AIM: To delineate indications and limitations for "extended" radical
      cholecystectomy for gallbladder cancer: a procedure which was instituted in our
      department in 1982. METHODS: Of 145 patients who underwent a radical resection
      for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical
      cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder
      fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second
      echelon node groups). A retrospective analysis of the 52 patients was conducted
      including at least 5 years of follow up. Residual tumor status was judged as no
      residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2).
      Pathological findings were documented according to the American Joint Committee
      on Cancer Cancer Staging Manual (7th edition). RESULTS: The primary tumor was
      classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4
      in 1. Twenty-three patients had lymph node metastases; 11 had a single positive
      node, 4 had two positive nodes, and 8 had three or more positive nodes. None of
      the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with
      pT2 or more advanced tumors had nodal disease. One patient died during the
      hospital stay for definitive resection, giving an in-hospital mortality rate of
      2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5
      years and 53% at 10 years in all 52 patients. OS differed according to the pT
      classification (P < 0.001) and the nodal status (P = 0.010). All of 3 patients
      with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more
      than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection,
      distant metastasis, or extensive extrahepatic organ involvement died soon after
      resection. Of the remaining four pT3 patients who had localized hepatic spread
      through the gallbladder fossa and underwent an R0 resection, 2 survived for more
      than 5 years and another survived for 4 years and 2 mo. The only patient with pT4
      tumor died of disease soon after resection. Among 23 node-positive patients, 11
      survived for more than 5 years, and of these, 10 had a modest degree of nodal
      disease (one or two positive nodes). CONCLUSION: Extended radical cholecystectomy
      is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion,
      provided that the regional nodal disease is limited to a modest degree (up to two
      positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease
      appears to be beyond the scope of this radical procedure.

PMID- 23002342
TI  - Titanium dioxide induced inflammation in the small intestine.
AB  - AIM: To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO2)
      and microparticles (MPTiO2) on the inflammatory response in the small intestine
      of mice. METHODS: Bl 57/6 male mice received distilled water suspensions
      containing TiO2 (100 mg/kg body weight) as NPTiO2 (66 nm), or MPTiO2 (260 nm) by
      gavage for 10 d, once a day; the control group received only distilled water. At
      the end of the treatment the duodenum, jejunum and ileum were extracted for
      assessment of cytokines, inflammatory cells and titanium content. The cytokines
      interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor
      necrosis factor-alpha (TNF-alpha), intracellular interferon-gamma (IFN-gamma) and
      transforming growth factor-beta (TGF-beta) were evaluated by enzyme-linked
      immunosorbent assay in segments of jejunum and ileum (mucosa and underlying
      muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic
      cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin
      by immunohistochemistry. The titanium content was determined by inductively
      coupled plasma atomic emission spectrometry. RESULTS: We found increased levels
      of T CD4+ cells (cells/mm2) in duodenum: NP 1240 +/- 139.4, MP 1070 +/- 154.7 vs
      458 +/- 50.39 (P < 0.01); jejunum: NP 908.4 +/- 130.3, MP 813.8 +/- 103.8 vs
      526.6 +/- 61.43 (P < 0.05); and ileum: NP 818.60 +/- 123.0, MP 640.1 +/- 32.75 vs
      466.9 +/- 22.4 (P < 0.05). In comparison to the control group, the groups
      receiving TiO2 showed a statistically significant increase in the levels of the
      inflammatory cytokines IL-12, IL-4, IL-23, TNF-alpha, IFN-gamma and TGF-beta. The
      cytokine production was more pronounced in the ileum (mean +/- SE): IL-12: NP
      33.98 +/- 11.76, MP 74.11 +/- 25.65 vs 19.06 +/- 3.92 (P < 0.05); IL-4: NP 17.36
      +/- 9.96, MP 22.94 +/- 7.47 vs 2.19 +/- 0.65 (P < 0.05); IL-23: NP 157.20 +/-
      75.80, MP 134.50 +/- 38.31 vs 22.34 +/- 5.81 (P < 0.05); TNFalpha: NP 3.71 +/-
      1.33, MP 5.44 +/- 1.67 vs 0.99 +/- 019 (P < 0.05); IFNgamma: NP 15.85 +/- 9.99,
      MP 34.08 +/- 11.44 vs 2.81 +/- 0.69 (P < 0.05); and TGF-beta: NP 780.70 +/-
      318.50, MP 1409.00 +/- 502.20 vs 205.50 +/- 63.93 (P < 0.05). CONCLUSION: Our
      findings indicate that TiO2 particles induce a Th1-mediated inflammatory response
      in the small bowel in mice.

PMID- 23002344
TI  - Clinicopathologic significance of expression of nuclear factor-kappaB RelA and
      its target gene products in gastric cancer patients.
AB  - AIM: To assess the prognostic significance of nuclear factor-kappaB (NF-kappaB)
      and its target genes in gastric cancer. METHODS: The tumor tissues of 115
      patients with gastric cancer were immunohistochemically evaluated using
      monoclonal antibodies against NF-kappaB RelA. Preoperative serum levels of
      vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via
      enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A
      (SAA) were measured via immunotrubidimetry. RESULTS: Positive rate of NF-kappaB
      RelA was 42.6%. NF-kappaB RelA expression in tumor tissues was also related to
      serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related
      to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL
      6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated
      that immunostaining of NF-kappaB RelA, levels of IL-6, VEGF, SAA were
      significantly related with both disease free survival and overall survival (OS).
      Multivariate analysis verified that NF-kappaB RelA [hazard ratio (HR): 3.40, P =
      0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS.
      CONCLUSION: Increased expression of NF-kappaB RelA and high levels of serum SAA
      were associated with poor OS in gastric cancer patients.

PMID- 23002345
TI  - Prognosis of hepatocellular carcinoma expressing cytokeratin 19: comparison with
      other liver cancers.
AB  - AIM: To investigate whether expressing biliary phenotype predicted poor outcome
      after the surgical treatment in primary liver cancers. METHODS: Out of 204
      patients that underwent liver resection due to hepatocellular carcinoma (HCC),
      liver specimens of 70 patients with HCC were evaluated for biliary components by
      cytokeratin (CK) 19 immunostain (CK19- HCC and CK19+ HCC). CK19 positivity was
      defined as membranous and/or cytoplasmic expression in >= 5% of tumor cells with
      moderate or strong intensity. Patients with other primary liver cancers, such as
      combined HCC and cholangiocarcinoma (cHCC-CC), intrahepatic cholangiocarcinoma
      (ICC) who received curative liver resection, were also included in the study.
      Clinical characteristics of CK19- HCC and CK19+ HCC patients, including survival
      outcome after curative liver resection, were compared with that of cHCC-CC and
      ICC patients. RESULTS: The overall survival (OS) rate of CK19- HCC (n = 49) after
      the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the
      resection. OS rate of CK19+ HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC
      (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1
      and 5-year-OS rate was 50.2% and 14.3% after the curative resection. The OS rates
      of CK19+ HCC and cHCC-CC were significantly lower than that of CK19- HCC, but
      higher than the OS rate of ICC (P = 0.000). There was no statistically
      significant difference in OS rate between CK19+ HCC and cHCC-CC. The disease free
      survival (DFS) rate of CK19- HCC was 72.0% and 54.5% at 1 and 3 years after the
      surgical treatment. DFS rate of CK19+ HCC was 53.3%, 34.3% and DFS rate of cHCC
      CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year
      DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19- HCC
      was significantly higher than that of ICC (P = 0.017), but marginally higher than
      DFS rate of either CK19+ HCC or cHCC-CC (P = 0.097, P = 0.089, respectively).
      Predictors of outcome after the surgery of primary liver cancer were pathology of
      the resected mass, existence of microvascular invasion and accompanying satellite
      nodule. CONCLUSION: Primary liver cancers with biliary components tended to show
      poorer surgical outcome. This suggested that immuno-phenotype of liver cancers
      was as important as their morphological classification.

PMID- 23002346
TI  - Association of fucosyltransferase 2 gene variants with ulcerative colitis in Han
      and Uyghur patients in China.
AB  - AIM: To investigate the contribution of fucosyltransferase 2 (FUT2) variants to
      the genetic susceptibility and clinical heterogeneity of ulcerative colitis (UC)
      between Han and Uyghur patients in Xinjiang, China. METHODS: A total of 102 UC
      patients (53 Han patients including 22 men and 31 women, and 49 Uyghur patients
      including 25 men and 24 women; aged 48 +/- 16 years) and 310 age- and sex-matched
      healthy controls were enrolled from January 2010 to May 2011 in Xinjiang People's
      Hospital of China. UC was diagnosed based on the clinical, endoscopic and
      histological findings following Lennard-Jones criteria. Blood samples were
      collected and genomic DNA was extracted by the routine laboratory methods.
      Polymerase chain reaction-sequence-based typing method was used to identify FUT2
      variants rs281377, rs1047781, rs601338 and rs602662. Genotypic and allelic
      frequencies were documented and compared between the UC patients and the healthy
      controls. Genotypic frequencies were also compared between Han and Uyghur
      patients. Potential association of genetic variation and UC between Han and
      Uyghur patients was examined. RESULTS: rs281377 was found significantly
      associated with UC in the Han population as compared with the controls (P =
      0.011) while rs281377 was not associated with UC in the Uyghur population (P =
      0.06). TT homozygous rs281377 frequencies were higher in the UC groups than in
      the controls (88.7% vs 68.7% and 55.1% vs 50.3%). rs1047781 was specifically
      associated with UC in the Uyghur population (P = 0.001), but not associated with
      UC in the Han population (P = 0.13). TT homozygous rs1047781 frequencies were
      lower in the UC groups than in the controls (9.5% vs 11.8% and 4.0% vs 6.7%).
      rs601338 was statistically related to UC in both populations (Han, P = 0.025;
      Uyghur, P = 8.33 * 10(-5)). AA homozygous rs601338 frequencies were lower in the
      UC groups than in the controls (0% vs 1.8% and 12.2% vs 13.4%). No association
      was found between rs602662 and UC in both Han and the Uyghur populations. Allelic
      analysis showed that rs281377 allele was significantly associated with UC in the
      Han population as compared with the controls [P = 0.001, odd ratio (OR) = 0.26],
      however, it was not associated with UC in the Uyghur population (P = 0.603, OR =
      1.14), and rs1047781 allele was associated with UC in the Uyghur population (P =
      0.001, OR = 0.029) while it was not associated with UC in the Han population (P =
      0.074, OR = 0.62). Moreover, rs601338 was associated with UC in both Han (P =
      0.005, OR = 0.1) and Uyghur populations (P = 0.002, OR = 0.43). Meta analysis
      showed that rs1047781 and rs601338 conferred risk of UC as compared with the
      controls [P = 0.005, OR = 0.47; P = 0.0003, OR = 0.35; 95% confidence interval
      (CI) = 0.31-0.72 and 0.21-0.58], but rs281377 and rs602662 showed no
      statistically significant differences between patients with UC and controls (P =
      0.10, OR = 0.71; P = 0.68, OR = 0.09; 95% CI = 0.47-1.07 and 0.56-1.47).
      CONCLUSION: Functionally relevant FUT2 gene variants are associated with UC,
      suggesting that they play a potential role in the pathogenesis of UC and may
      contribute to the clinical heterogeneity of UC between Han and Uyghur patients.

PMID- 23002347
TI  - Emergency transcatheter arterial embolization for patients with acute massive
      duodenal ulcer hemorrhage.
AB  - AIM: To evaluate the efficacy and safety of emergency transcatheter arterial
      embolization (ETAE) for patients with acute massive duodenal ulcer hemorrhage.
      METHODS: Twenty-nine consecutive patients with acute massive bleeding of duodenal
      ulcer were admitted to our hospital from 2006 to 2011. Superselective angiography
      of the celiac and gastroduodenal arteries was performed to find out the bleeding
      sites before ETAE, then, embolotherapy was done with gelatin sponge particles or
      microstrips via a 5 French angiographic catheter or 3 French microcatheter. After
      ETAE, further superior mesenteric arteriography was undertaken in case collateral
      circulation supplied areas of the duodenal ulcer. Technical and clinical success
      rates were analyzed. Changes in the mucous membrane were observed using endoscopy
      following ETAE. RESULTS: Angiography showed active bleeding with extravasation of
      contrast medium in seven cases with a 24% positive rate of celiac artery
      bleeding, and in 19 cases with a 65.5% rate of gastroduodenal artery bleeding.
      There were no angiographic signs of bleeding in three patients who underwent
      endoscopy prior to ETAE. Twenty-six patients achieved immediate hemostasis and
      technical success rate reached 90%. No hemostasis was observed in 27 patients
      within 30 d after ETAE and clinical success rate was 93%. Recurrent hemorrhage
      occurred in two patients who drank a lot of wine who were treated by a second
      embolotherapy in the same way. Five patients underwent transient ischem with
      light abdominal pain under xiphoid, spontaneous restoration without special
      treatment. No mucous necrosis happened to 29 cases for ischem of gastroduodenal
      arteries embolized. CONCLUSION: ETAE is an effective and safe measure to control
      acute massive bleeding of duodenal ulcer.

PMID- 23002348
TI  - Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and
      confocal laser endomicroscopy.
AB  - AIM: To evaluate the diagnosis of different differentiated gastric
      intraepithelial neoplasia (IN) by magnification endoscopy combined with narrow
      band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS: Eligible
      patients with suspected gastric IN lesions previously diagnosed by endoscopy in
      secondary hospitals and scheduled for further diagnosis and treatment were
      recruited for this study. Excluded from the study were patients who had liver
      cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding,
      coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded
      were those who were pregnant, breastfeeding, were younger than 18 years old, or
      were unable to provide informed consent. All patients had all mucus and bile
      cleared from their stomachs. They then received upper GI endoscopy. When a
      mucosal lesion is found during observation with white-light imaging, the lesion
      is visualized using maximal magnification, employing gradual movement of the tip
      of the endoscope to bring the image into focus. Saved images are analyzed.
      Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were
      familiar with CLE, blinded to the related information about the lesions, and
      asked to classify each lesion as either a low grade dysplasia (LGD) or high grade
      dysplasia (HGD) according to given criteria. The results were compared with the
      final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists
      (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related
      information about the lesions and CLE images, and were asked to classify each
      lesion as a LGD or HGD according to the "microvascular pattern and surface
      pattern" classification system. The results were compared with the final
      histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low
      grade gastric IN and 26 pathology-proven high grade gastric IN that were detected
      with any of the modalities. CLE and ME-NBI enabled clear visualization of the
      vascular microsurface patterns and microvascular structures of the gastric
      mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI: 78%
      98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement
      between the histopathology and the in vivo CLE imaging was 0.755; between the
      histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial
      distribution used) indicated that the agreement was significant (P < 0.05). When
      patients were diagnosed by ME-NBI with CLE, the overall accuracy of the diagnosis
      was 86.21% (95% CI: 73%-96%), and the kappa coefficient of agreement was 0.713,
      according to McNemar's test (P < 0.05). CONCLUSION: Higher diagnostic accuracy,
      sensitivity and specificity of CLE over ME-NBI indicate the feasibility of these
      two techniques for the efficacious diagnostic classification of gastric IN.

PMID- 23002349
TI  - Hyperthermia inhibits hypoxia-induced epithelial-mesenchymal transition in HepG2
      hepatocellular carcinoma cells.
AB  - AIM: To investigate the effect of hyperthermia on hypoxia-induced epithelial
      mesenchymal transition (EMT) in HepG2 hepatocellular carcinoma (HCC) cells, and
      its mechanism. METHODS: Cells were treated with hyperthermia at 43  degrees C for
      0.5 h, followed by incubation under hypoxic or normoxic conditions for 72 h. Cell
      morphology was observed. Expressions of E-cadherin and vimentin were determined
      by immunofluorescence assay or Western blot. The protein and mRNA expressions of
      Snail were also determined by Western blot and reverse transcription-polymerase
      chain reaction. Cell migratory capacity was evaluated. RESULTS: Hypoxia induced
      EMT in HepG2 cells, which was evidenced by morphological, molecular and
      functional changes, including the formation of a spindle shape and the loss of
      cell contact. The expression of E-cadherin was decreased but the expression of
      vimentin was increased; also, the migratory capability was increased by 2.2 +/-
      0.20-fold as compared with normoxia. However, those effects were inhibited by
      hyperthermia pretreatment. Furthermore, protein synthesis and mRNA expression of
      Snail in the cells were enhanced by hypoxia as compared with normoxia, and also
      significantly inhibited by hyperthermia pretreatment. CONCLUSION: Hyperthermia
      may inhibit hypoxia-induced EMT in HepG2 HCC cells, and the mechanism may involve
      inhibition of induced expression of Snail.

PMID- 23002350
TI  - Angioedema associated with Crohn's disease: response to biologics.
AB  - A 46-year-old female patient with terminal ileum Crohn's disease and ankylosing
      spondylitis presented with recurrent angioedema and urticaria. Investigations
      ruled out hereditary angioedema, and environmental or food allergen triggers. She
      was diagnosed with chronic idiopathic urticaria with angioedema, and was treated
      with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and
      hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on
      infliximab infusions and within 2 treatments, she had complete resolution of the
      angioedema and urticaria, as well as of the bowel and arthritic symptoms.
      Unfortunately she developed allergic reactions to the infliximab and was switched
      to another anti-tumor necrosis factor (TNF)-alpha agent, adalimumab. Since then,
      she has had no further angioedema or urticaria, and her Crohn's disease has been
      quiescent. This is the first known case report of chronic idiopathic urticaria
      with angioedema coexistent with Crohn's disease that was successfully treated
      with anti-TNF-alpha agents.

PMID- 23002351
TI  - Catheter-directed thrombolysis in inflammatory bowel diseases: report of a case.
AB  - In patients with inflammatory bowel diseases (IBD) the prevalence of thrombosis
      is 6.2%, the average incidence of thromboembolism (TE) is 3.6 times higher
      compared to normal population. The TE is a common extraintestinal complication of
      IBD, squarely associated with the IBD activity. The application of anticoagulant
      and thrombolytic therapy in severe IBD is an unresolved issue. Herein we report
      the first case in literature of an active IBD patient with an upper limb acute
      arterial occlusion and successful catheter-directed thrombolysis (CDT). A 46-year
      old male patient is reported who had Crohn's disease for 10 years. His right hand
      suddenly became cold and painful. Angiography proved acute occlusion of the
      brachial and radial artery. Vascular surgery intervention was not applicable.
      Endoscopy showed extended, severe inflammation of the colon. Despite the severe
      endoscopic findings, frequent bloody stools and moderate anaemia, CDT with
      recombinant tissue plasminogen activator was performed. The control angiography
      proved improvement, the radial artery pulse appeared. No bleeding complication
      was observed. This case supports that CDT-after careful estimation of the
      bleeding risk-can be effective and safe in patients with severe or life
      threatening TE and active IBD.

PMID- 23002352
TI  - Development of perianal ulcer as a result of acute fulminant amoebic colitis.
AB  - We report a case of acute fulminant amoebic colitis that resulted in the
      development of a perianal ulcer in a 29-year-old Japanese homosexual man with
      acquired immunodeficiency syndrome (AIDS). The patient was admitted to our
      hospital with a persistent perianal abscess that was refractory to antibiotic
      therapy administered at another hospital. On admission, we observed a giant ulcer
      in the perianal region. At first, cytomegalovirus colitis was suspected by blood
      investigations. Ganciclovir therapy was initiated; however, the patient developed
      necrosis of the skin around the anus during therapy. We only performed end
      sigmoidostomy and necrotomy to avoid excessive surgical invasion.
      Histopathological examination of the surgical specimen revealed the presence of
      trophozoite amoebae, indicating a final diagnosis of acute fulminant amoebic
      colitis. The patient's postoperative course was favorable, and proctectomy of the
      residual rectum was performed 11 mo later. Amoebic colitis is one of the most
      severe complications affecting patients with AIDS. Particularly, acute fulminant
      amoebic colitis may result in a poor prognosis; therefore, staged surgical
      therapy as a less invasive procedure should be considered as one of the treatment
      options for these patients.

PMID- 23002353
TI  - A pedunculated polyp-shaped small-bowel lymphangioma causing gastrointestinal
      bleeding and treated by double-balloon enteroscopy.
AB  - We report a rare case of a small-bowel lymphangioma causing massive
      gastrointestinal (GI) bleeding that we successfully diagnosed and treated using
      double-balloon enteroscopy (DBE). An 81-year-old woman suffering from repeated GI
      bleeding of unknown origin underwent a capsule endoscopy at a previous hospital.
      She was suspected of having bleeding from the jejunum, and was referred to our
      department for diagnosis and treatment. An oral DBE revealed a 20 mm * 10 mm,
      regularly surfaced, white to yellowish, elongated, pedunculated jejunal polyp
      with small erosions at 10 cm distal to the ligament of Treiz. Since no other
      source of bleeding was identified by endoscopy in the deep jejunum, an endoscopic
      polypectomy (EP) was performed for this lesion. A subsequent histopathological
      examination of the resected polyp showed clusters of lymphatic vessels with
      marked cystic dilatation in the submucosa and the deep layer of the lamina
      propria mucosae. These characteristics are consistent with the typical features
      of small-bowel lymphangioma with erosions. Although clipping hemostasis was
      performed during EP, re-bleeding occurred. Finally, a complete hemostasis was
      achieved by performing an additional argon plasma coagulation.

PMID- 23002354
TI  - Biliary cysts: etiology, diagnosis and management.
AB  - Biliary cysts (BC) are rare dilatations of different parts of a biliary tract.
      They account for approximately 1% of all benign biliary diseases. BC occur the
      most frequently in Asian and female populations. They are an important problem
      for pediatricians, gastroenterologists, radiologists and surgeons. Clinical
      presentation and management depend on the BC type. Cholangiocarcinoma is the most
      serious and dangerous BC complication. The other complications associated with BC
      involve cholelithiasis and hepatolithiasis, cholangitis, acute and chronic
      pancreatitis, portal hypertension, liver fibrosis and secondary liver cirrhosis
      and spontaneous cyst perforation. Different BC classifications have been
      described in the literature. Todani classification dividing BC into five types is
      the most useful in clinical practice. The early diagnosis and proper treatment
      are very important, because BC are associated with a risk of carcinogenesis. A
      malignancy risk increases with the age. Radiological investigations
      (ultrasonography, computed tomography, endoscopic retrograde
      cholangiopancreatography and magnetic resonance cholangiopancreatography) play an
      important role in BC diagnostics. Currently, prenatal diagnosis using
      ultrasonography is possible. It allows to differentiate biliary disorders in
      fetals and to perform the early surgical treatment that improves results. In most
      patients, total cyst excision with Roux-Y hepaticojejunostomy is the treatment of
      choice. Surgical treatment of BC is associated with high success rate and low
      morbidity and mortality. The early treatment is associated with a lower number of
      complications. Patients following BC surgery require permanent and careful
      postoperative observation using laboratory and imaging investigations because of
      possibility of biliary anastomosis stricture and biliary cancer in tissue
      remnant.

PMID- 23002355
TI  - Quality of ulcer healing in gastrointestinal tract: its pathophysiology and
      clinical relevance.
AB  - In this paper, we review the concept of quality of ulcer healing (QOUH) in the
      gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic
      ulcer disease (PUD) has been a chronic disease with a cycle of repeated
      healing/remission and recurrence. The main etiological factor of PUD is
      Helicobacter pylori (H. pylori), which is also the cause of ulcer recurrence.
      However, H. pylori-negative ulcers are present in 12%-20% of patients; they also
      recur and are on occasion intractable. QOUH focuses on the fact that mucosal and
      submucosal structures within ulcer scars are incompletely regenerated. Within the
      scars of healed ulcers, regenerated tissue is immature and with distorted
      architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can
      be the basis for ulcer recurrence. Our studies have shown that persistence of
      macrophages in the regenerated area plays a key role in ulcer recurrence. Our
      studies in a rat model of ulcer recurrence have indicated that proinflammatory
      cytokines trigger activation of macrophages, which in turn produce increased
      amounts of cytokines and chemokines, which attract neutrophils to the regenerated
      area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting
      in ulcer recurrence. Another important factor in poor QOUH can be deficiency of
      endogenous prostaglandins and a deficiency and/or an imbalance of endogenous
      growth factors. Topically active mucosal protective and antiulcer drugs promote
      high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In
      addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel
      diseases including Crohn's disease and ulcerative colitis.

PMID- 23002356
TI  - Use of the tumor necrosis factor-blockers for Crohn's disease.
AB  - The use of anti-tumor necrosis factor-alpha therapy for inflammatory bowel
      disease represents the most important advance in the care of these patients since
      the publication of the National Co-operative Crohn's disease study thirty years
      ago. The recommendations of numerous consensus groups worldwide are now supported
      by a wealth of clinical trials and several meta-analyses. In general, it is
      suggested that tumor necrosis factor-alpha blockers (TNFBs) are indicated (1) for
      persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who
      have failed two or more causes of glucocorticosteroids and an acceptably long
      cause (8 wk to 12 wk) of an immune modulator such as azathioprine or
      methotrexate; (2) non-responsive perianal disease; and (3) severe UC not
      responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced
      and the patient is responsive, therapy given by the IV and SC rate must be
      continued. It remains open to definitive evidence if concomitant immune
      modulators are required with TNFB maintenance therapy, and when or if TNFB may be
      weaned and discontinued. The supportive evidence from a single study on the role
      of early versus later introduction of TNFB in the course of a patient's illness
      needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable
      as long as the patient is immunized and tested for tuberculosis and viral
      hepatitis before the initiation of TNFB, and as long as the long-term adverse
      effects on the development of lymphoma and other tumors do not prone to be
      problematic. Because the rates of benefits to TNFB are modest from a population
      perspective and the cost of therapy is very high, the ultimate application of use
      of TNFBs will likely be established by cost/benefit studies.

PMID- 23002357
TI  - Role for mycobacterial infection in pathogenesis of primary biliary cirrhosis?
AB  - Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease
      characterized by the immune-mediated destruction of biliary epithelial cells in
      small intrahepatic bile ducts. The disease is characterized by circulating
      antimitochondrial antibodies (AMAs) as well as disease-specific antinuclear
      antibodies, cholestatic liver function tests, and characteristic histological
      features, including granulomas. A variety of organisms are involved in granuloma
      formation, of which mycobacteria are the most commonly associated. This has led
      to the hypothesis that mycobacteria may be involved in the pathogenesis of PBC,
      along with other infectious agents. Additionally, AMAs are found in a subgroup of
      patients with mycobacterial infections, such as leprosy and pulmonary
      tuberculosis. Antibodies against species-specific mycobacterial proteins have
      been reported in patients with PBC, but it is not clear whether these antibodies
      are specific for the disease. In addition, data in support of the involvement of
      the role of molecular mimicry between mycobacterial and human mitochondrial
      antigens as triggers of cross-reactive immune responses leading to the loss of
      immunological tolerance, and the induction of pathological features have been
      published. Thus, antibodies against mycobacterial heat shock protein appear to
      cross-recognize AMA-specific autoantigens, but it is not clear whether these
      autoantibodies are mycobacterium-species-specific, and whether they are
      pathogenic or incidental. The view that mycobacteria are infectious triggers of
      PBC is intriguing, but the data provided so far are not conclusive.

PMID- 23002358
TI  - Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal
      adenocarcinogenesis in rats.
AB  - AIM: To evaluate the effects of indomethacin [dual cyclooxygenase (COX)-1/COX-2
      inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)-2-(5H)
      furanone (MF-tricyclic) (COX-2 selective inhibitor) in a rat experimental model
      of Barrett's esophagus and esophageal adenocarcinoma. METHODS: A total of 112
      surviving post-surgery rats were randomly divided into three groups: the control
      group (n = 48), which did not receive any treatment; the indomethacin group (n =
      32), which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor; and the MF
      tricyclic group (n = 32), which received 10 mg/kg per day of the selective COX-2
      inhibitor. Randomly selected rats were killed either 8 wk or 16 wk after surgery.
      The timing of the deaths was in accordance with a previous study performed in our
      group. Only rats that were killed at the times designated by the protocol were
      included in the study. We then assessed the histology and prostaglandin E2 (PGE2)
      expression levels in the rat esophagi. An additional group of eight animals that
      did not undergo esophagojejunostomy were included in order to obtain normal
      esophageal tissue as a control. RESULTS: Compared to a control group with no
      treatment (vehicle-treated rats), indomethacin treatment was associated with
      decreases in ulcerated esophageal mucosa (16% vs 35% and 14% vs 17%, 2 mo and 4
      mo after surgery, respectively; P = 0.021), length of intestinal metaplasia in
      continuity with anastomosis (2 +/- 1.17 mm vs 2.29 +/- 0.75 mm and 1.25 +/- 0.42
      mm vs 3.5 +/- 1.54 mm, 2 mo and 4 mo after surgery, respectively; P = 0.007),
      presence of intestinal metaplasia beyond anastomosis (20% vs 71.4% and 0% vs 60%,
      2 mo and 4 mo after surgery, respectively; P = 0.009), severity of dysplasia (0%
      vs 71.4% and 20% vs 85.7% high-grade dysplasia, 2 mo and 4 mo after surgery,
      respectively; P = 0.002), and adenocarcinoma incidence (0% vs 57.1% and 0% vs
      60%, 2 mo and 4 mo after surgery, respectively; P < 0.0001). Treatment with the
      selective COX-2 inhibitor, MF-tricyclic, did not prevent development of
      intestinal metaplasia or adenocarcinoma. In parallel, we observed a significant
      decrease in PGE2 levels in indomethacin-treated rats, but not in those treated
      with MF-tricyclic, at both 2 mo and 4 mo. Compared to control rats that did not
      undergo surgery (68 +/- 8 ng/g, P = 0.0022 Kruskal-Wallis test) there was a
      significant increase in PGE2 levels in the esophageal tissue of the rats that
      underwent surgery either 2 mo (1332 +/- 656 ng/g) or 4 mo (1121 +/- 1015 ng/g)
      after esophagojejunostomy. However, no differences were found when esophageal
      PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy. At both the 2-
      and 4-mo timepoints, we observed a significant decrease in PGE2 levels in
      indomethacin-treated rat esophagi compared to those in either the control or MF
      tricyclic groups (P = 0.049 and P = 0.017, respectively). No differences in PGE2
      levels were found when we compared levels in rats treated with MF-tricyclic to
      not-treated rats. CONCLUSION: In this rat model of gastrointestinal reflux,
      indomethacin was associated with a decrease in the severity of esophagitis and
      reduced development of esophageal intestinal metaplasia and adenocarcinoma.

PMID- 23002360
TI  - Clinical usefulness of adherence to gastro-esophageal reflux disease guideline by
      Spanish gastroenterologists.
AB  - AIM: To investigate usefulness of adherence to gastro-esophageal reflux disease
      (GERD) guideline established by the Spanish Association of Gastroenterology.
      METHODS: Prospective, observational and multicentre study of 301 patients with
      typical symptoms of GERD who should be managed in accordance with guidelines and
      were attended by gastroenterologists in daily practice. Patients (aged > 18
      years) were eligible for inclusion if they had typical symptoms of GERD
      (heartburn and/or acid regurgitation) as the major complaint in the presence or
      absence of accompanying atypical symptoms, such as dyspeptic symptoms and/or
      supraesophageal symptoms. Diagnostic and therapeutic decisions should be made
      based on specific recommendations of the Spanish clinical practice guideline for
      GERD which is a widely disseminated and well known instrument among Spanish in
      digestive disease specialists. RESULTS: Endoscopy was indicated in 123 (41%)
      patients: 50 with alarm symptoms, 32 with age > 50 years without alarm symptom.
      Seventy-two patients (58.5%) had esophagitis (grade A, 23, grade B, 28, grade C,
      18, grade D, 3). In the presence of alarm symptoms, endoscopy was indicated
      consistently with recommendations in 98% of cases. However, in the absence of
      alarm symptoms, endoscopy was indicated in 33% of patients > 50 years (not
      recommended by the guideline). Adherence for proton pump inhibitors (PPIs)
      therapy was 80%, but doses prescribed were lower (half) in 5% of cases and higher
      (double) in 15%. Adherence regarding duration of PPI therapy was 69%; duration
      was shorter than recommended in 1% (4 wk in esophagitis grades C-D) or longer in
      30% (8 wk in esophagitis grades A-B or in patients without endoscopy). Treatment
      response was higher when PPI doses were consistent with guidelines, although
      differences were not significant (95% vs 85%). CONCLUSION: GERD guideline
      compliance was quite good although endoscopy was over indicated in patients > 50
      years without alarm symptoms; PPIs were prescribed at higher doses and longer
      duration.

PMID- 23002359
TI  - Effect of tangweian jianji on upper gastrointestinal remodeling in streptozotocin
      induced diabetic rats.
AB  - AIM: To investigate the effect of Tangweian Jianji (TWAJJ) on the biomechanical
      and morphometrical remodeling of the upper gastrointestinal tract in diabetic
      rats. METHODS: Diabetes was induced in 27 rats by injecting streptozotocin (40
      mg/kg body weight), the animals were then divided into three groups (n = 9 in
      each group), i.e., diabetic control (DM); high dose (10 g/kg, T1) and low dose (5
      g/kg, T2). Another 10 rats acted as normal controls (Control). TWAJJ was
      administered by gavage once daily. Blood glucose and serum insulin levels were
      measured. Circumferential length, wall thickness and opening angle were measured
      from esophageal, duodenal, jejunal and ileal ring segments. The residual strain
      was calculated from the morphometric data. Step-wise distension was carried out
      on esophageal and jejunal segments. The obtained data on the length, diameter and
      pressure changes were then used to calculate the circumferential and longitudinal
      stresses and strains. Real-time reverse transcription polymerase chain reaction
      was used to detect the receptor of advanced glycation end-products (RAGE) mRNA
      level in jejunal tissues. RESULTS: At the end of the experiment, the blood
      glucose level was significantly higher and the serum insulin level was
      significantly lower in DM, T1 and T2 groups than in the control group (Glucose:
      30.23 +/- 0.41 mmol/L, 27.48 +/- 0.27 mmol/L and 27.84 +/- 0.29 mmol/L vs 5.05 +/
      0.04 mmol/L, P = 1.65 * 10(-16), P = 5.89 * 10(-19) and P = 1.63 * 10(-18),
      respectively; Insulin: 1.47 +/- 0.32 MUg/L, 2.66 +/- 0.44 MUg/L, 2.03 +/- 0.29
      MUg/L and 4.17 +/- 0.54 MUg/L, P = 0.0001, P = 0.029 and P = 0.025,
      respectively). However, these levels did not differ among the DM, T1 and T2
      groups. The wet weight per unit length, wall thickness and opening angle of
      esophageal and intestinal segments in the DM group were significantly higher than
      those in the control group (from P = 0.009 to P = 0.004). These parameters in the
      T1 group were significantly lower than those in the DM group (wet weight,
      duodenum: 0.147 +/- 0.003 g/cm vs 0.158 +/- 0.001 g/cm, P = 0.047; jejunum, 0.127
      +/- 0.003 g/cm vs 0.151 +/- 0.002 g/cm, P = 0.017; ileum, 0.127 +/- 0.004 g/cm vs
      0.139 +/- 0.003 g/cm, P = 0.046; wall thickness, esophagus: 0.84 +/- 0.03 mm vs
      0.94 +/- 0.02 mm, P = 0.014; duodenum: 1.27 +/- 0.06 mm vs 1.39 +/- 0.05 mm, P =
      0.031; jejunum: 1.19 +/- 0.07 mm vs 1.34 +/- 0.04 mm, P = 0.047; ileum: 1.09 +/-
      0.04 mm vs 1.15 +/- 0.03 mm, P = 0.049; opening angle, esophagus: 112.2 +/- 13.2
      vs 134.7 +/- 14.7, P = 0.027; duodenum: 105.9 +/- 12.3 vs 123.1 +/- 13.1, P =
      0.046; jejunum: 90.1 +/- 15.4 vs 115.5 +/- 13.3, P = 0.044; ileum: 112.9 +/- 13.4
      vs 136.1 +/- 17.1, P = 0.035). In the esophageal and jejunal segments, the inner
      residual stain was significantly smaller and the outer residual strain was larger
      in the DM group than in the control group (P = 0.022 and P = 0.035). T1 treatment
      significantly restored this biomechanical alteration (P = 0.011 and P = 0.019),
      but T2 treatment did not. Furthermore, the circumferential and longitudinal
      stiffness of the esophageal and jejunal wall increased in the DM group compared
      with those in the control group. T1, but not T2 treatment, significantly
      decreased the circumferential wall stiffness in the jejunal segment (P = 0.012)
      and longitudinal wall stiffness in the esophageal segment (P = 0.023). The mRNA
      level of RAGE was significantly decreased in the T1 group compared to that in the
      DM group (P = 0.0069). CONCLUSION: TWAJJ (high dose) treatment partly restored
      the morphometric and biomechanical remodeling of the upper gastrointestinal tract
      in diabetic rats.

PMID- 23002361
TI  - IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C.
AB  - AIM: To evaluate the effect of single nucleotide polymorphisms of interleukin
      (IL)-28B, rs12979860 on progression and treatment response in chronic hepatitis
      C. METHODS: Patients (n = 64; 37 men, 27 women; mean age, 44 +/- 12 years) with
      chronic hepatitis C, genotype 1, received treatment with peg-interferon plus
      ribavirin. Genotyping of rs12979860 was performed on peripheral blood DNA.
      Histopathological assessment of necroinflammatory grade and fibrosis stage were
      scored using the METAVIR system on a liver biopsy sample before treatment. Serum
      viral load, aminotransferase activity, and insulin level were measured. Insulin
      resistance index, body mass index, waist/hip ratio, percentage of body fat and
      fibrosis progression rate were calculated. Applied dose of interferon and
      ribavirin, platelet and neutrophil count and hemoglobin level were measured.
      RESULTS: A sustained virological response (SVR) was significantly associated with
      IL28B polymorphism (CC vs TT allele: odds ratio (OR), 25; CC vs CT allele: OR,
      5.4), inflammation activity (G < 1 vs G > 1: OR, 3.9), fibrosis (F < 1 vs F > 1:
      OR, 5.9), platelet count (> 200 * 10(9)/L vs < 200 * 10(9)/L: OR, 4.7; OR in
      patients with genotype CT: 12.8), fatty liver (absence vs presence of steatosis:
      OR, 4.8), insulin resistance index (< 2.5 vs > 2.5: OR, 3.9), and baseline HCV
      viral load (< 10(6) IU/mL vs > 10(6) IU/mL: OR, 3.0). There was no association
      with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or
      percentage body fat. There was borderline significance (P = 0.064) of increased
      fibrosis in patients with the TT allele, and no differences in the insulin
      resistance index between groups of patients with CC, CT and TT alleles (P =
      0.12). Spearman's rank correlation coefficient between insulin resistance and
      stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively
      (P < 0.001). Significant differences were found in the insulin resistance index
      (P = 0.01) between patients with and without steatosis. Patients with the CT
      allele and absence of a SVR had a higher incidence of requiring threshold dose
      reduction of interferon (P = 0.07). CONCLUSION: IL28B variation is the strongest
      host factor not related to insulin resistance that determines outcome of
      antiviral therapy. Baseline platelet count predicts the outcome of antiviral
      therapy in CT allele patients.

PMID- 23002362
TI  - Analysis of colonoscopic perforations at a local clinic and a tertiary hospital.
AB  - AIM: To define the clinical characteristics, and to assess the management of
      colonoscopic complications at a local clinic. METHODS: A retrospective review of
      the medical records was performed for the patients with iatrogenic colon
      perforations after endoscopy at a local clinic between April 2006 and December
      2010. Data obtained from a tertiary hospital in the same region were also
      analyzed. The underlying conditions, clinical presentations, perforation
      locations, treatment types (operative or conservative) and outcome data for
      patients at the local clinic and the tertiary hospital were compared. RESULTS: A
      total of 10  826 colonoscopies, and 2625 therapeutic procedures were performed at
      a local clinic and 32  148 colonoscopies, and 7787 therapeutic procedures were
      performed at the tertiary hospital. The clinic had no perforations during
      diagnostic colonoscopy and 8 (0.3%) perforations were determined to be related to
      therapeutic procedures. The perforation rates in each therapeutic procedure were
      0.06% (1/1609) in polypectomy, 0.2% (2/885) in endoscopic mucosal resection
      (EMR), and 3.8% (5/131) in endoscopic submucosal dissection (ESD). Perforation
      rates for ESD were significantly higher than those for polypectomy or EMR (P <
      0.01). All of these patients were treated conservatively. On the other hand,
      three (0.01%) perforation cases were observed among the 24  361 diagnostic
      procedures performed, and these cases were treated with surgery in a tertiary
      hospital. Six perforations occurred with therapeutic endoscopy (perforation rate,
      0.08%; 1 per 1298 procedures). Perforation rates for specific procedure types
      were 0.02% (1 per 5500) for polypectomy, 0.17% (1 per 561) for EMR, 2.3% (1 per
      43) for ESD in the tertiary hospital. There were no differences in the
      perforation rates for each therapeutic procedure between the clinic and the
      tertiary hospital. The incidence of iatrogenic perforation requiring surgical
      treatment was quite low in both the clinic and the tertiary hospital. No
      procedure-related mortalities occurred. Performing closure with endoscopic
      clipping reduced the C-reactive protein (CRP) titers. The mean maximum CRP titer
      was 2.9 +/- 1.6 mg/dL with clipping and 9.7 +/- 6.2 mg/dL without clipping,
      respectively (P < 0.05). An operation is indicated in the presence of a large
      perforation, and in the setting of generalized peritonitis or ongoing sepsis.
      Although we did not experience such case in the clinic, patients with large
      perforations should be immediately transferred to a tertiary hospital. Good
      relationships between local clinics and nearby tertiary hospitals should
      therefore be maintained. CONCLUSION: It was therefore found to be possible to
      perform endoscopic treatment at a local clinic when sufficient back up was
      available at a nearby tertiary hospital.

PMID- 23002363
TI  - High-risk esophageal varices in patients treated with locoregional therapy for
      hepatocellular carcinoma: assessment with liver computed tomography.
AB  - AIM: To assess the diagnostic performance of follow-up liver computed tomography
      (CT) for the detection of high-risk esophageal varices in patients treated with
      locoregional therapy for hepatocellular carcinoma (HCC). METHODS: We
      prospectively enrolled 100 patients with cirrhosis who underwent transcatheter
      arterial chemoembolization, radiofrequency ablation or both procedures for HCCs.
      All patients underwent upper endoscopy and subsequently liver CT. Three
      radiologists independently evaluated the presence of high-risk esophageal varices
      with transverse images alone and with three orthogonal multiplanar reformation
      (MPR) images, respectively. With endoscopic grading as the reference standard,
      diagnostic performance was assessed by using receiver operating characteristic
      (ROC) curve analysis. RESULTS: The diagnostic performances (areas under the ROC
      curve) of three observers with transverse images alone were 0.947 +/- 0.031,
      0.969 +/- 0.024, and 0.916 +/- 0.038, respectively. The mean sensitivity,
      specificity, positive predicative value (PPV), and negative predicative value
      (NPV) with transverse images alone were 90.1%, 86.39%, 70.9%, and 95.9%,
      respectively. The diagnostic performances, mean sensitivity, specificity, PPV,
      and NPV with three orthogonal MPR images (0.965 +/- 0.025, 0.959 +/- 0.027, 0.938
      +/- 0.033, 91.4%, 89.5%, 76.3%, and 96.6%, respectively) were not superior to
      corresponding values with transverse images alone (P > 0.05), except for the mean
      specificity (P = 0.039). CONCLUSION: Our results showed excellent diagnostic
      performance, sensitivity and NPV to detect high-risk esophageal varices on follow
      up liver CT after locoregional therapy for HCC.

PMID- 23002364
TI  - Pentoxifylline in hepatopulmonary syndrome.
AB  - AIM: To determine the effects of pentoxifylline (PTX) on clinical manifestations
      and evaluate arterial blood gas data in hepatopulmonary syndrome (HPS) in
      children. METHODS: In a pilot study of 10 children with chronic liver disease,
      who had HPS, 20 mg/kg/d PTX was administered for 3 mo. Clinical data and arterial
      blood gas parameters were evaluated at baseline, the end of the treatment period,
      and 3 mo after drug discontinuation. RESULTS: Six patients could tolerate PTX,
      while four patients experienced complications. Among patients who could tolerate
      PTX, there was a significant increase in arterial oxygen pressure (PaO(2)) (P =
      0.02) and oxygen saturation (SaO(2)) (P = 0.04) and alveolar-arterial oxygen
      gradient (P = 0.02) after 3 mo of treatment. Significant decreases in PaO(2) (P =
      0.02) and alveolar-arterial oxygen gradient (P = 0.02) were also seen after drug
      discontinuation. CONCLUSION: PTX may improve PaO(2), SaO(2) and alveolar-arterial
      oxygen gradient in the early stage of HPS.

PMID- 23002366
TI  - Endothelial precursor cells promote angiogenesis in hepatocellular carcinoma.
AB  - AIM: To investigate the role of bone marrow-derived endothelial progenitor cells
      (EPCs) in the angiogenesis of hepatocellular carcinoma (HCC). METHODS: The bone
      marrow of HCC mice was reconstructed by transplanting green fluorescent protein
      (GFP) + bone marrow cells. The concentration of circulating EPCs was determined
      by colony-forming assays and fluorescence-activated cell sorting. Serum and
      tissue levels of vascular endothelial growth factor (VEGF) and colony-stimulating
      factor (CSF) were quantified by enzyme-linked immunosorbent assay. The
      distribution of EPCs in tumor and tumor-free tissues was detected by
      immunohistochemistry and real-time polymerase chain reaction. The incorporation
      of EPCs into hepatic vessels was examined by immunofluorescence and
      immunohistochemistry. The proportion of EPCs in vessels was then calculated.
      RESULTS: The HCC model was successful established. The flow cytometry analysis
      showed the mean percentage of CD133CD34 and CD133VEGFR2 double positive cells in
      HCC mice was 0.45% +/- 0.16% and 0.20% +/- 0.09% respectively. These values are
      much higher than in the sham-operation group (0.11% +/- 0.13%, 0.05% +/- 0.11%, n
      = 9) at 14 d after modeling. At 21 d, the mean percentage of circulating
      CD133CD34 and CD133VEGFR2 cells is 0.23% +/- 0.19%, 0.25% +/- 0.15% in HCC model
      vs 0.05% +/- 0.04%, 0.12% +/- 0.11% in control. Compared to the transient
      increase observed in controls, the higher level of circulating EPCs were induced
      by HCC. In addition, the level of serum VEGF and CSF increased gradually in HCC,
      reaching its peak 14 d after modeling, then slowly decreased. Consecutive
      sections stained for the CD133 and CD34 antigens showed that the CD133+ and CD34+
      VEGFR2 cells were mostly recruited to HCC tissue and concentrated in tumor
      microvessels. Under fluorescence microscopy, the bone-marrow (BM)-derived cells
      labeled with GFP were concentrated in the same area. The relative levels of CD133
      and CD34 gene expression were elevated in tumors, around 5.0 and 3.8 times that
      of the tumor free area. In frozen liver sections from HCC mice, cells co
      expressing CD133 and VEGFR2 were identified by immunohistochemical staining using
      anti-CD133 and VEGFR2 antibodies. In tumor tissue, the double-positive cells were
      incorporated into vessel walls. In immunofluorescent staining. These CD31 and GFP
      double positive cells are direct evidence that tumor vascular endothelial cells
      (VECs) come partly from BM-derived EPCs. The proportion of GFP CD31 double
      positive VECs (out of all VECs) on day 21 was around 35.3% +/- 21.2%. This is
      much higher than the value recorded on day 7 group (17.1% +/- 8.9%). The
      expression of intercellular adhesion molecule 1, vascular adhesion molecule 1,
      and VEGF was higher in tumor areas than in tumor-free tissues. CONCLUSION:
      Mobilized EPCs were found to participate in tumor vasculogenesis of HCC.
      Inhibiting EPC mobilization or recruitment to tumor tissue may be an efficient
      strategy for treating HCC.

PMID- 23002365
TI  - Inducible nitric oxide synthetase genotype and Helicobacter pylori infection
      affect gastric cancer risk.
AB  - AIM: To investigate the association of the inducible nitric oxide synthetase
      (iNOS) C150T polymorphism with Helicobacter pylori (H. pylori) infection and
      gastric cancer (GC) risk in Iran. METHODS: In order to determine whether there
      was a correlation between iNOS genotype and GC in Iran, we conducted a case
      control study using samples from 329 individuals. For each sample, the C150T iNOS
      polymorphism was genotyped by polymerase chain reaction (PCR) and restriction
      digestion. Patients were grouped by cancer presence, demographic and behavior
      characteristics, and H. pylori infection status. Statistical tests were conducted
      to determine whether any behavioral factors or a particular iNOS genotype was
      associated with GC in the study population. RESULTS: In this population, we found
      that smoking, hot beverage consumption, a familial history of GC and H. pylori
      infection status were significantly associated with GC development (P = 0.015, P
      < 0.001, P = 0.0034, and P < 0.015, respectively). The distribution of the C150T
      iNOS genotypes among the two study groups was not statistically significant
      alone, but was impacted by H. pylori infection status. When compared to the non
      H. pylori infected group, cancer patients who had a heterozygous CT genotype and
      were also infected with H. pylori were 2.1 times more at risk of developing GC
      [odds ratio (OR) = 2.1, P = 0.03] while those with a homozygous TT genotype and
      infected with H. pylori were 5.0 times more at risk of developing GC (OR = 5.0, P
      = 0.029). In contrast, this association was not seen in patients in the control
      group. CONCLUSION: A CT or TT polymorphism at position 150 in the iNOS gene
      significantly increases the risk of GC and may be a marker for GC susceptibility.

PMID- 23002367
TI  - Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces
      severe liver damage in a rat model.
AB  - AIM: To investigate the correlation of hyperlipemia (HL) and acute cerebral
      ischemia/reperfusion (I/R) injury on liver damage and its mechanism. METHODS:
      Rats were divided into 4 groups: control, HL, I/R and HL+I/R. After the induction
      of HL via a high-fat diet for 18 wk, middle cerebral artery occlusion was
      followed by 24 h of reperfusion to capture I/R. Serum alanine transaminase (ALT)
      and aspartate aminotransferase (AST) were analyzed as part of liver function
      tests and liver damage was further assessed by histological examination.
      Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP
      nick-end labeling (TUNEL) assay. The expression of genes related to apoptosis
      (caspase-3, bcl-2) was assayed by immunohistochemistry and Western blotting.
      Serum tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and liver
      mitochondrial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px),
      malondialdehyde (MDA) and Ca(2+) levels were measured to determine inflammatory
      and oxidative/antioxidative status respectively. Microsomal hydroxylase activity
      of the cytochrome P450 2E1 (CYP2E1)-containing enzyme was measured with aniline
      as the substrate, and CYP2E1 expression in the liver tissue and microsome was
      determined by immunohistochemistry and Western blotting respectively. RESULTS: HL
      alone induced by high-fat diet for 18 wk resulted in liver damage, indicated by
      histopathological analysis, and a considerable increase in serum ALT (25.13 +/-
      16.90 vs 9.56 +/- 1.99, P < 0.01) and AST levels (18.01 +/- 10.00 vs 11.33 +/-
      4.17, P < 0.05) compared with control. Moreover, HL alone induced hepatocyte
      apoptosis, which was determined by increased TUNEL-positive cells (4.47 +/- 0.45
      vs 1.5 +/- 0.22, P < 0.01), higher caspase-3 and lower bcl-2 expression.
      Interestingly, compared with those in control, HL or I/R groups, massive
      increases of serum ALT (93.62 +/- 24.00 vs 9.56 +/- 1.99, 25.13 +/- 16.90 or
      12.93 +/- 6.14, P < 0.01) and AST (82.32 +/- 26.92 vs 11.33 +/- 4.17, 18.01 +/-
      10.00 or 14.00 +/- 6.19, P < 0.01) levels in HL+I/R group were observed
      suggesting severe liver damage, which was confirmed by liver histology. In
      addition, HL combined with I/R also caused significantly increased hepatocyte
      apoptosis, as evidenced by increased TUNEL-positive cells (6.20 +/- 0.29 vs 1.5
      +/- 0.22, 4.47 +/- 0.45 or 1.97 +/- 0.47, P < 0.01), elevated expression of
      caspase-3 and lower expression of bcl-2. Furthermore, when compared to HL or I/R
      alone, HL plus I/R enhanced serum TNF-alpha, IL-1, liver mitochondrial MDA and
      Ca(2+) levels, suppressed SOD and GSH-Px in liver mitochondria, and markedly up
      regulated the activity (11.76 +/- 2.36 vs 4.77 +/- 2.31 or 3.11 +/- 1.35, P <
      0.01) and expression (3.24 +/- 0.38 vs 1.98 +/- 0.88 or 1.72 +/- 0.58, P < 0.01)
      of CYP2E1 in liver. CONCLUSION: The coexistence of HL and acute cerebral I/R
      induces severe liver damage, suggesting that cerebral ischemic stroke would
      exaggerate the damage of liver caused by HL. This effect is possibly due to
      enhanced CYP2E1 induction which further promotes oxidative damage, inflammation
      and hepatocyte apoptosis.

PMID- 23002369
TI  - Cameron ulcers: an atypical source for a massive upper gastrointestinal bleed.
AB  - Cameron lesions represent linear gastric erosions and ulcers on the crests of
      mucosal folds in the distal neck of a hiatal hernia (HH). Such lesions may be
      found in upto 50% of endoscopies performed for another indication. Though
      typically asymptomatic, these may rarely present as acute, severe upper
      gastrointestinal bleed (GIB). The aim is to report a case of a non-anemic 87-year
      old female with history of HH and atrial fibrillation who presented with
      hematemesis and melena resulting in hypovolemic shock. Repeat
      esophagogastroduodenoscopy was required to identify multiple Cameron ulcers as
      the source. Endoscopy in a patient with HH should involve meticulous
      visualization of hernia neck and surrounding mucosa. Cameron ulcers should be
      considered in all patients with severe, acute GIB and especially in those with
      known HH with or without chronic anemia.

PMID- 23002368
TI  - Does gemcitabine-based combination therapy improve the prognosis of unresectable
      pancreatic cancer?
AB  - AIM: To assess whether gemcitabine-based combination therapy improves the
      prognosis of unresectable pancreatic cancer compared with gemcitabine treatment
      alone. METHODS: A quantitative up-to-date meta-analysis was undertaken to
      investigate the efficacy of gemcitabine-based combination treatment compared with
      gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.
      Inclusion was limited to high-quality randomized clinical trials. RESULTS: Twenty
      six studies were included in the present analysis, with a total of 8808 patients
      recruited. The studies were divided into four subgroups based on the different
      kinds of cytotoxic agents, including platinum, fluoropyrimidine, camptothecin and
      targeted agents. Patients treated with gemcitabine monotherapy had significantly
      lower objective response rate [risk ratio (RR), 0.72; 95% confidence interval
      (CI): 0.63-0.83; P < 0.001], and lower 1-year overall survival (RR, 0.90; 95%CI:
      0.82-0.99; P = 0.04). Gemcitabine monotherapy caused fewer complications,
      including fewer grade 3-4 toxicities: including vomiting (RR, 0.75; 95%CI: 0.62
      0.89; P = 0.001), diarrhea (RR, 0.66; 95%CI: 0.49-0.89; P = 0.006), neutropenia
      (RR, 0.88; 95%CI: 0.72-1.06; P = 0.18), anemia (RR, 0.96; 95%CI: 0.82-1.12; P =
      0.60), and thrombocytopenia (RR, 0.76; 95%CI: 0.60-0.97; P = 0.03) compared with
      gemcitabine combination therapies. CONCLUSION: Gemcitabine combination therapy
      provides a modest improvement of survival, but is associated with more toxicity
      compared with gemcitabine monotherapy.

PMID- 23002370
TI  - Metastases of esophageal carcinoma to skeletal muscle: single center experience.
AB  - Metastases of esophageal carcinoma to the skeletal muscle are rare, but the
      incidence may be increasing because of better diagnosis resulting from widespread
      use of positron emission tomography/computed tomography (PET/CT). A cohort of 205
      patients with esophageal carcinoma treated at our center who had PET/CT between
      2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle
      metastases. Four patients had skeletal muscle metastases of esophageal carcinoma,
      including two patients with squamous cell carcinoma. In another patient with
      squamous cell carcinoma of the esophagus and synchronous skeletal muscle
      metastases, muscle metastases were subsequently shown to be related to second
      primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were
      the first manifestation of systemic disease. In three patients palliation was
      obtained with the combination of external beam radiation therapy, systemic
      chemotherapy or surgical resection. Skeletal muscle metastases are a rare
      complication of esophageal carcinoma.

PMID- 23002371
TI  - Hepatic schwannoma: imaging findings on CT, MRI and contrast-enhanced
      ultrasonography.
AB  - A primary benign schwannoma of the liver is extremely rare and is difficult to
      preoperatively discriminate from a malignant tumor. We compared the imaging and
      pathological findings, and examined the possibility of preoperatively diagnosing
      a benign liver schwannoma. A 72-year-old woman was admitted to our hospital
      because of a 4.6-cm mass in the liver. A malignant tumor was suspected, and a
      right hepatectomy was performed. After this, the diagnosis of a primary benign
      schwannoma of the liver was made through pathological examination. Contrast
      enhanced ultrasonography (CEUS) with Sonazoid showed minute blood flows into the
      septum and solid areas of the tumor in the vascular phase; most likely due to
      increased arterial flow associated with infiltration of chronic inflammatory
      cells. In the postvascular phase, CEUS showed contrast defect of cystic areas and
      delayed enhancement of solid areas; most likely due to aggregation of
      siderophores. Because discriminating between a benign and malignant schwannoma of
      the liver is difficult, surgery is generally recommended. However, the two key
      findings from CEUS may be useful in discriminating ancient schwannoma by
      recognizing the hemorrhage involved in the secondary degeneration and aggregation
      of siderophores.

PMID- 23002372
TI  - Hypertension in response to IL-6 during pregnancy: role of AT1-receptor
      activation.
AB  - BACKGROUND: Increases in interleukin 6 (IL-6) and agonistic autoantibodies to the
      angiotensin II type 1 receptor (AT1-AA) are proposed to be important links
      between placental ischemia and hypertension in preeclampsia.  METHODS: The
      purpose of this study was to determine whether IL-6 (5 ng/day), infused into
      normal pregnant (NP) rats, increased mean arterial pressure (MAP) and AT1-AA. MAP
      was analyzed in the presence and absence of an angiotensin type 1 receptor (AT1R)
      antagonist, losartan, L.  RESULTS: MAP and AT1-AA increased from 102 +/- 2 to 118
      +/- 4 mmHg and 0.7 +/- 0.3 NP to 14.1 +/- 1.4 chronotropic units with chronic IL
      6 infusion. MAP responses to IL-6 were abolished in losartan pretreated rats (85
      +/- 4 in NP + L vs 85 +/- 3 mmHg in IL-6 + L).  CONCLUSION: These data indicate
      that IL-6 stimulates AT1-AA and that activation of the AT1R mediates IL-6 induced
      hypertension during pregnancy.

PMID- 23002373
TI  - Ablation procedures for rhythm control in patients with atrial fibrillation:
      clinical and cost-effectiveness analyses.

PMID- 23002374
TI  - Clopidogrel versus Other Antiplatelet Agents for Secondary Prevention of Vascular
      Events in Adults with Acute Coronary Syndrome or Peripheral Vascular Disease:
      Clinical and Cost-Effectiveness Analyses.

PMID- 23002375
TI  - Clopidogrel compared with other antiplatelet agents for secondary prevention of
      vascular events in adults undergoing percutaneous coronary intervention: clinical
      and cost-effectiveness analyses.

PMID- 23002376
TI  - 1.5 tesla magnetic resonance imaging scanners compared with 3.0 tesla magnetic
      resonance imaging scanners: systematic review of clinical effectiveness.

PMID- 23002377
TI  - Optimal therapy recommendation for the use of solvent/detergent-treated human
      plasma.

PMID- 23002378
TI  - Robot-assisted surgery compared with open surgery and laparoscopic surgery.

PMID- 23002379
TI  - Combination and high-dose atypical antipsychotic therapy in patients with
      schizophrenia: systematic review.

PMID- 23002380
TI  - Physical interventions to interrupt or reduce the spread of respiratory viruses -
      resource use implications: a systematic review.

PMID- 23002381
TI  - Pharmacologic-based strategies for smoking cessation: clinical and cost
      effectiveness analyses.

PMID- 23002382
TI  - Optimal warfarin management for the prevention of thromboembolic events in
      patients with atrial fibrillation: a systematic review of the clinical evidence.

PMID- 23002383
TI  - Management of Cancer Related Distress in Patients with a Hematological
      Malignancy.
AB  - Patients with hematologic malignancies often require urgent, aggressive, and
      lengthy chemotherapy treatment. These treatment regimens, divided into cycles,
      result in extended, often isolating periods of hospitalization where any direct
      clinical benefit for the patient, such as remission or "no evidence of disease"
      is not immediately declared. Consequently, this population is at a high risk of
      experiencing severe levels of cancer related distress. Cancer related distress is
      a complex psychosocial phenomenon that has consequences for patients, their
      families as well as the healthcare staff. Thus the importance of prevention,
      early recognition, treatment and management is unquestionable. Nurses have an
      important role to help identify and manage the presence of cancer related
      distress in these patients, as well as their family's. Nurses should work
      proactively in close partnership with an interdisciplinary team to effectively
      provide the necessary support for patients experiencing or who are at risk for
      high levels of cancer related distress. This case study and subsequent discussion
      illustrates the symptom management needs and challenges related to cancer related
      distress in the patient with a hematologic malignancy. Current evidence-based
      practice guidelines for the assessment and management of cancer related distress
      will be presented.

PMID- 23002384
TI  - A rapid genotyping assay for segregating human olfactory receptor pseudogenes.
AB  - Variation in odor perception between individuals is initiated by binding of
      "odorant" molecules to olfactory receptors (ORs) located in the nasal cavity. To
      determine the mechanism for variation in odor perception, identification of
      specific ligands for a large number of ORs is required. However, it has been
      difficult to identify specific ligands, and ligands have been identified for only
      2-3% of the hundreds of mammalian ORs. One way to increase the number of
      identified ligands is to take advantage of >60 human OR genes that are
      segregating as a result of a single nucleotide polymorphism, between a functional
      intact allele and a nonfunctional pseudogene allele. Potential ligands for these
      ORs can be identified by correlating odor perception of an individual with their
      genotype [intact/intact (I/I) vs. pseudogene/pseudogene (P/P)] for an OR gene.
      For this type of study, genotypes must be determined for a large number of
      individuals. We have developed a PCR-based assay to distinguish between the
      intact and pseudogene alleles of 49 segregating human OR genes and to determine
      an individual's genotype for these genes. To facilitate rapid determination of
      genotypes for a large number of individuals, the assay uses a small number of
      simple steps and equipment commonly found in most molecular biology and
      biochemistry laboratories. Although this assay was developed to distinguish
      between polymorphisms in OR genes, it can easily be adapted for use in
      distinguishing single nucleotide polymorphisms in any gene or chromosomal locus.

PMID- 23002385
TI  - Major extremity injuries associated with farmyard accidents.
AB  - BACKGROUND: The aim of the study is to analyze the major agricultural injuries
      related to the extremities. PATIENTS: We evaluated a 3-year period including 41
      patients. Data on age, sex, injury patterns, anatomical localizations, injury
      season, length of stay in the hospital, and infections were evaluated, and the
      patients were examined with SF-36 in the follow-up period. RESULTS: Hand was the
      most commonly injured part (n: 9) followed by the distal part of the lower limb
      (cruris) (n: 7) and foot (n: 7). Mean time between trauma and emergency
      department arrival was 115 minutes (60-360). Mean length of stay was 24 days (4
      150), and mean number of operations during hospitalization was 2.4 (1-30). Deep
      wound infection was seen in 8 patients. Seasonal distribution for accidents was
      even for spring and fall (27% each), high for summer (36%), and less for winter
      (10%). CONCLUSIONS: Distal parts of the elbow and knee were affected more
      frequently. Due to the high microbiological load and high incidence of crush-type
      injuries, repetitive debridements and long duration of hospital stay were needed.
      Attention should be paid in the harvesting times to the farmyard injuries. Due to
      the seasonal variation, more resources should be allocated to treat the
      increasing incidence of injury over the period from spring to fall.

PMID- 23002386
TI  - An evaluation of the responsiveness and discriminant validity of shoulder
      questionnaires among patients receiving surgical correction of shoulder
      instability.
AB  - Health-related quality-of-life (HRQL) measures must detect clinically important
      changes over time and between different patient subgroups. Forty-three patients
      (32 M, 13 F; mean age = 26.00 +/- 8.19 years) undergoing arthroscopic Bankart
      repair completed three validated shoulder questionnaires (Western Ontario
      Shoulder Instability index (WOSI), American Shoulder and Elbow Surgeons
      Standardized Shoulder Assessment form (ASES), Constant score) preoperatively, and
      at 6, 12, and 24 months postoperatively. Responsiveness and discriminant validity
      was assessed between those with a satisfactory outcome and those with (1) a major
      recurrence of instability, (2) a single episode of subluxation, (3) any
      postoperative episode of instability. Eight (20%) patients reported recurrent
      instability. Compared to baseline, the WOSI detected improvement at the 6- (P <
      0.001) and 12-month (P = 0.011) evaluations. The ASES showed improvement at 6
      months (P = 0.003), while the Constant score did not report significant
      improvement until 12 months postoperatively (P = 0.001). Only the WOSI detected
      differential shoulder function related to shoulder instability. Those
      experiencing even a single episode of subluxation reported a 10% drop in their
      WOSI score, attaining the previously established minimal clinically important
      difference (MCID). Those experiencing a frank dislocation or multiple episodes of
      subluxation reported a 20% decline. The WOSI allows better discrimination of the
      severity of postoperative instability symptoms following arthroscopic Bankart
      repair.

PMID- 23002387
TI  - Alfa-lipoic acid controls tumor growth and modulates hepatic redox state in
      Ehrlich-ascites-carcinoma-bearing mice.
AB  - The effect of oral supplementation of alpha-lipoic (LA) on growth of Ehrlich
      ascites carcinoma cells (EACs) and hepatic antioxidant state in mice was
      investigated. The results revealed that alpha-lipoic (LA) acid at 50 mg/kg body
      wt reduced the viability and volume of EAC cells and increased the survival of
      the treated animals. In addition, LA normalized oxidative stress in liver of mice
      bearing EAC cells evidenced by increasing the levels of total thiols,
      glutathione, glutathione-S-transferase, superoxide dismutase, and catalyse. On
      the other hand, significant decreases in the levels of malondialdehyde and
      protein carbonyl were demonstrated in liver indicating controlled oxidative
      stress in these animals. As a consequence, LA regulated liver enzymes, alkaline
      phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma
      glutamyl transferase. The data also indicated the efficiency of LA as cancer
      inhibitor and therapeutic influence. In conclusion, the present data suggest LA
      as a potential therapeutic complement in the treatment or prevention of different
      pathologies that may be related to an imbalance of the cellular oxidoreductive
      status associated with malignancy.

PMID- 23002388
TI  - Random amplified polymorphic markers as indicator for genetic conservation
      program in Iranian pheasant (Phasianus colchicus).
AB  - The objective of present study was identification of genetic similarity between
      wild Iran and captive Azerbaijan Pheasant using PCR-RAPD markers. For this
      purpose, in overall, 28 birds were taken for DNA extraction and subsequently 15
      arbitrary primers were applied for PCR-RAPD technique. After electrophoresis,
      five primers exhibited sufficient variability which yielded overall 65 distinct
      bands, 59 polymorphic bands, for detalis, range of number of bands per primer was
      10 to 14, and produced size varied between 200 to 1500 bp. Highest and lowest
      polymorphic primers were OPC5, OPC16 (100%) and OPC15 (81%), respectively. Result
      of genetic variation between two groups was accounted as nonsignificant (8.12%)
      of the overall variation. According to our expectation the wild Iranian birds
      showed higher genetic diversity value than the Azerbaijan captive birds. As
      general conclusion, two pheasant populations have almost same genetic origin and
      probably are subpopulations of one population. The data reported herein could
      open the opportunity to search for suitable conservation strategy to improve
      richness of Iran biodiversity and present study here was the first report that
      might have significant impact on the breeding and conservation program of Iranian
      pheasant gene pool. Analyses using more regions, more birds, and more DNA markers
      will be useful to confirm or to reject these findings.

PMID- 23002389
TI  - Predicting ion-nucleic acid interactions by energy landscape-guided sampling.
AB  - The recently developed Tightly Bound Ion (TBI) model offers improved predictions
      for ion effect in nucleic acid systems by accounting for ion correlation and
      fluctuation effects. However, further application of the model to larger systems
      is limited by the low computational efficiency of the model. Here, we develop a
      new computational efficient TBI model using free energy landscape-guided sampling
      method. The method leads to drastic reduction in the computer time by a factor of
      50 for RNAs of 50-100 nucleotides long. The improvement in the computational
      efficiency would be more significant for larger structures. To test the new
      method, we apply the model to predict the free energies and the number of bound
      ions for a series of RNA folding systems. The validity of this new model is
      supported by the nearly exact agreement with the results from the original TBI
      model and the agreement with the experimental data. The method may pave the way
      for further applications of the TBI model to treat a broad range of biologically
      significant systems such as tetraloop-receptor and riboswitches.

PMID- 23002390
TI  - Gene Signatures in Stage II Colon Cancer: A Clinical Review.
AB  - Understanding the biology of cancer is the key to understanding its behavior.
      Stage II colon cancers represent a unique treatment challenge for medical
      oncologists because they contain a very heterogeneous group of tumors with a wide
      range of recurrence risks after resection. Defining these differences in biology
      can help to explain differences in behavior. To this end, gene signatures have
      been developed to define various prognostic groups beyond the clinicopathologic
      features alone. Adjuvant chemotherapy for stage II colon cancers as a group has
      not shown survival advantage in clinical trials. Future research to develop gene
      signatures to predict a group that will benefit from adjuvant chemotherapy will
      be helpful in the clinical decision-making process. The purpose of this review is
      to present the prognostic gene signatures currently available for use, those in
      development, and their utility in stratifying recurrence risk in stage II colon
      cancer patients.

PMID- 23002392
TI  - Choroidal neovascular membrane formation and retinochoroidopathy in a patient
      with systemic langerhans cell histiocytosis: a case report and review of the
      literature.
AB  - We report a case of bilateral atrophic retinochoroidopathy with choroidal
      neovascular membrane (CNVM) formation in a patient with systemic Langerhans cell
      histiocytosis (LCH). A 35-year-old female, diagnosed with LCH at the age of 3,
      experienced an episode of acute vision loss in her right eye. Visual acuity was
      counting fingers. Dilated fundus exam and fluorescein angiography revealed the
      presence of CNVM along with bilateral widespread areas of chorioretinal atrophy.
      The patient underwent removal of CNVM with excellent postoperative visual acuity
      (20/25); however, indolent progression of her disease led to gradual
      deterioration of visual acuity (20/80 in the right eye and 20/320 in the left).
      This case shows that in contrast to previous reports, intraocular involvement of
      LCH does not need to be dramatic and clinically evident but it can acquire a
      chronic degenerative form. This report aims to raise awareness among
      ophthalmologists concerning the potential intraocular sequelae of LCH.

PMID- 23002391
TI  - Bioinformatics Tools for Mass Spectrometry-Based High-Throughput Quantitative
      Proteomics Platforms.
AB  - Determining global proteome changes is important for advancing a systems biology
      view of cellular processes and for discovering biomarkers. Liquid chromatography,
      coupled to mass spectrometry, has been widely used as a proteomics technique for
      discovering differentially expressed proteins in biological samples. However,
      although a large number of high-throughput studies have identified differentially
      regulated proteins, only a small fraction of these results have been reproduced
      and independently verified. The use of different approaches to data processing
      and analyses is among the factors which contribute to inconsistent conclusions.
      This perspective provides a comprehensive and critical overview of bioinformatics
      methods for commonly used mass spectrometry-based quantitative proteomics,
      employing both stable isotope labeling and label-free approaches. We evaluate the
      challenges associated with current quantitative proteomics techniques, placing
      particular emphasis on data analyses. The complexity of processing and
      interpreting proteomics datasets has become a central issue as sensitivity, mass
      resolution, mass accuracy and throughput of mass spectrometers have improved. A
      number of computer programs are available to address these challenges, and are
      reviewed here. We focus on approaches for signal processing, noise reduction, and
      methods for protein abundance estimation.

PMID- 23002393
TI  - Clinical data mining of phenotypic network in angina pectoris of coronary heart
      disease.
AB  - Coronary heart disease (CHD) is the leading causes of morbidity and mortality in
      China. The diagnosis of CHD in Traditional Chinese Medicine (TCM) was mainly
      based on experience in the past. In this paper, we proposed four MI-based
      association algorithms to analyze phenotype networks of CHD, and established
      scale of syndromes to automatically generate the diagnosis of patients based on
      their phenotypes. We also compared the change of core syndromes that CHD were
      combined with other diseases, and presented the different phenotype spectra.

PMID- 23002394
TI  - A Novel Technique for Micro-patterning Proteins and Cells on Polyacrylamide Gels.
AB  - Spatial patterning of proteins (extracellular matrix, ECM) for living cells on
      polyacrylamide (PA) hydrogels has been technically challenging due to the
      compliant nature of the hydrogels and their aqueous environment. Traditional
      micro-fabrication process is not applicable. Here we report a simple, novel and
      general method to pattern a variety of commonly used cell adhesion molecules,
      i.e. Fibronectin (FN), Laminin (LN) and Collagen I (CN), etc. on PA gels. The
      pattern is first printed on a hydrophilic glass using polydimethylsiloxane (PDMS)
      stamp and micro-contact printing (MUCP). Pre-polymerization solution is applied
      on the patterned glass and is then sandwiched by a functionalized glass slide,
      which covalently binds to the gel. The hydrophilic glass slide is then peeled off
      from the gel when the protein patterns detach from the glass, but remain intact
      with the gel. The pattern is thus transferred to the gel. The mechanism of
      pattern transfer is studied in light of interfacial mechanics. It is found that
      hydrophilic glass offers strong enough adhesion with ECM proteins such that a
      pattern can be printed, but weak enough adhesion such that they can be completely
      peeled off by the polymerized gel. This balance is essential for successful
      pattern transfer. As a demonstration, lines of FN, LN and CN with widths varying
      from 5-400 MUm are patterned on PA gels. Normal fibroblasts (MKF) are cultured on
      the gel surfaces. The cell attachment and proliferation are confined within these
      patterns. The method avoids the use of any toxic chemistry often used to pattern
      different proteins on gel surfaces.

PMID- 23002395
TI  - Non-affine deformations in polymer hydrogels.
AB  - Most theories of soft matter elasticity assume that the local strain in a sample
      after deformation is identical everywhere and equal to the macroscopic strain, or
      equivalently that the deformation is affine. We discuss the elasticity of
      hydrogels of crosslinked polymers with special attention to affine and non-affine
      theories of elasticity. Experimental procedures to measure non-affine
      deformations are also described. Entropic theories, which account for gel
      elasticity based on stretching out individual polymer chains, predict affine
      deformations. In contrast, simulations of network deformation that result in
      bending of the stiff constituent filaments generally predict non-affine behavior.
      Results from experiments show significant non-affine deformation in hydrogels
      even when they are formed by flexible polymers for which bending would appear to
      be negligible compared to stretching. However, this finding is not necessarily an
      experimental proof of the non-affine model for elasticity. We emphasize the
      insights gained from experiments using confocal rheoscope and show that, in
      addition to filament bending, sample micro-inhomogeneity can be a significant
      alternative source of non-affine deformation.

PMID- 23002396
TI  - Victimization and PTSD in A Rural Kenyan Youth Sample.
AB  - Within the last ten years, there has been a growing number of epidemiological
      studies, examining the effect of trauma exposure in children and adolescents.
      Although studies concerning Post-traumatic Stress Disorder (PTSD) have been
      conducted in a wide array of different cultural contexts [1], the knowledge on
      traumatization and development of PTSD is still limited [2]. Most studies
      conducted are clinical studies, which deal with subjects that have already been
      traumatized or affected by specific single events such as war [3], natural
      disasters [1], serious accidents [4] or physical/sexual abuse [5-7]. Though
      research indicates that adolescents are very vulnerable to the exposure of
      Potentially Traumatic Events (PTEs) [8], studies targeting non-clinical youth
      populations and the impact of their life experiences are very few. With the
      increasing ethnic diversity of populations worldwide, it is of particular
      interest to compare the prevalence of exposure and PTSD in children and
      adolescents of different ethnic backgrounds. When designing preventive
      interventions and treatment programs for youth suffering from PTSD it is crucial
      to understand the complex interaction of variables behind the disorder.
      Differences in prevalence of exposure, PTSD and demographic variables between
      ethnicities may reveal some important clues to the etiology of the disease.The
      present study replicated six previous non-clinical studies which were designed to
      provide epidemiological information about exposure to PTEs, and the prevalence of
      PTSD among adolescents (see Table 1). The six studies were conducted in different
      countries and were very similar in their research methods and samples. The
      studies have been conducted in four European countries: Denmark [9], Iceland,
      [10], Lithuania [11], and the Faroe Islands [2], as well as in two Asian
      countries: Israel [12], and India [13] of which the four first samples were
      nationally representative.

PMID- 23002397
TI  - A survey of pharmaceutical company representative interactions with doctors in
      Libya.
AB  - OBJECTIVES: To examine the frequency of pharmaceutical company representative
      (PCR) interactions with doctors in Libya and review possible associations between
      these interactions and the personal and practice setting characteristics of
      doctors. METHOD: An anonymous survey questionnaire was circulated to 1,000 Libyan
      doctors in selected public and private practice settings in Tripoli, Benghazi and
      Sebha. RESULTS: A questionnaire return rate of 61% (608 returned questionnaires)
      was achieved. Most respondents (94%) reported that they had been visited by PCRs
      at least 'once' in the last year. Fifty per cent of respondents met with PCRs at
      least once a month, and 20% at least once a week. The following characteristics
      were significantly associated with meeting with a representative more than once a
      week: age, gender (male > female), years of practice, being a specialist (other
      than an anaesthesiologist) or working in private practice. Ninety-one per cent of
      doctors reported that they had received at least one kind of relationship gift
      during the last year. Printed materials (79%), simple gifts (73%) and drug
      samples (69%) were the most common relationship products given to respondents.
      Reimbursements or sponsored items were reported by 33% of respondents. Physician
      specialists were more likely to receive drug samples or sponsored items than
      residents, general practitioners, anaesthesiologists or surgeons (P<0.01).
      Participants working in private practice alone or in both sectors were more
      likely to receive printed materials, simple gifts or free samples from PCRs than
      doctors working in the public sector (P<0.05). CONCLUSION: Libyan doctors are
      frequently visited by PCRs. Doctors, working in private practice or specialist
      practice, are especially targeted by promotional activities. An agreed code of
      conduct for pharmaceutical promotion in Libya between doctors and PCRs should be
      created.

PMID- 23002398
TI  - Microtubule Tip Tracking and Tip Structures at the Nanometer Scale Using Digital
      Fluorescence Microscopy.
AB  - Microtubules (MTs) are central to fundamental cellular processes including
      mitosis, polarization, and axon extension. A key issue is to understand how MT
      associated proteins and therapeutic drugs, such as the anticancer drug
      paclitaxel, control MT self-assembly. To facilitate this research, it would be
      helpful to have automated methods that track the tip of dynamically assembling
      MTs as observed via fluorescence microscopy. Through a combination of digital
      fluorescence imaging with MT modeling, model-convolution, and automated image
      analysis of live and fixed MTs, we developed a method for MT tip tracking that
      includes estimation of the measurement error. We found that the typical single
      frame tip tracking accuracy of GFP-tubulin labeled MTs in living LLC-PK1alpha
      cells imaged with a standard widefield epifluorescence digital microscope system
      is ~36 nm, the equivalent of ~4.5 tubulin dimer layers. However, if the MT tips
      are blunt, the tip tracking accuracy can be as accurate as ~15 nm (~2 dimer
      layers). By fitting a Gaussian survival function to the MT tip intensity
      profiles, we also established that MTs within living cells are not all blunt, but
      instead exhibit highly variable tapered tip structures with a protofilament
      length standard deviation of ~180 nm. More generally, the tip tracking method can
      be extended to track the tips of any individual fluorescently labeled filament,
      and can estimate filament tip structures both in vivo and in vitro with single
      frame accuracy on the nanoscale.

PMID- 23002399
TI  - Mechanical tension modulates local and global vesicle dynamics in neurons.
AB  - Growing experimental evidence suggests that mechanical tension plays a
      significant role in determining the growth, guidance, and function of neurons.
      Mechanical tension in axons contributes to neurotransmitter clustering at the
      Drosophila neuromuscular junction (NMJ) and is actively regulated by neurons both
      in vitro and in vivo. In this work, we applied mechanical strain on in vivo
      Drosophila neurons and in vitro Aplysia neurons and studied their vesicle
      dynamics by live-imaging. Our experiments show that mechanical stretch modulates
      the dynamics of vesicles in two different model systems: (1) The global
      accumulation of synaptic vesicles (SV) at the Drosophila NMJ and (2) the local
      motion of individual large dense core vesicles (LDCV) in Aplysia neurites.
      Specifically, a sustained stretch results in enhanced SV accumulation in the
      Drosophila NMJ. This increased SV accumulation occurs in the absence of
      extracellular Ca(2+), plateaus after approximately 50 min, and persists for at
      least 30 min after stretch is reduced. On the other hand, mechanical compression
      in Aplysia neurites immediately disrupts LDCV motion, leading to decreased range
      and processivity. This impairment of LDCV motion persists for at least 15 min
      after tension is restored. These results show that mechanical stretch modulates
      both local and global vesicle dynamics and strengthens the notion that tension
      serves a role in regulating neuronal function.

PMID- 23002400
TI  - Magnesium sulfate treatment improves outcome in patients with subarachnoid
      hemorrhage: a meta-analysis study.
AB  - OBJECTIVE: To elucidate the role of magnesium sulfate in patients with
      subarachnoid hemorrhagic (SAH) brain injury METHOD: Studies for the meta-analysis
      were identified from PubMed (1966 to 2009), Embase (1980 to 2009), and two
      Chinese journals (1989 to 2009). Paper selection was based on randomized
      controlled trials comparing magnesium sulfate to placebo treatment in patients
      with SAH. Two independent review authors extracted the data and assessed trial
      quality. Meta-analysis was performed using the Cochrane Review Manger software.
      RESULTS: Five trials involving 482 patients were included in the review.
      Magnesium sulfate reduced the risk of poor outcome and reduced the occurrence of
      delayed cerebral ischemia. In the treatment groups, relative risk for poor
      outcome was 0.73 (CI 0.57-0.93) and 0.66 (CI 0.47-0.92) for delayed cerebral
      ischemia. Case fatality assessment at three to six months did not show
      statistically significant data (RR 0.88; CI 0.61-1.29). CONCLUSION: Magnesium
      sulfate appears to be an effective treatment option in the management of SAH.
      Further clinical trials are needed before magnesium sulfate can become a routine
      treatment for SAH.

PMID- 23002401
TI  - Ferumoxytol-enhanced MRI to Image Inflammation within Human Brain Arteriovenous
      Malformations: A Pilot Investigation.
AB  - Inflammation cell infiltration and cytokine expression are seen in the vascular
      walls and intervening stroma of resected brain arteriovenous malformation (bAVM)
      specimens, even in unruptured and previously untreated lesions. Macrophages may
      play a critical role in bAVM progression to rupture, and could serve as a marker
      for rupture risk. We assessed feasibility of imaging macrophages within the bAVM
      nidus using ferumoxytol-enhanced MRI in four patients with already diagnosed
      bAVMs using iron-sensitive imaging (ISI; T2*-GE-MRI sequence). Patients were
      imaged at baseline and at either 1 day (n=2) or 5 days (n=2) after infusion of
      5mg/kg of ferumoxytol. Residual intravascular ferumoxytol obscured evaluation for
      uptake in bAVM vascular walls and stroma at the 1-day time point. The two cases
      imaged at 5 days showed less intravascular tracer but had signal loss in the
      nidal region consistent with ferumoxytol localization. One case underwent
      surgical resection; there was prominent vascular wall CD68 staining. Ferumoxytol
      enhanced-MRI for assessing bAVM inflammatory cell burden appears feasible and has
      the potential to be developed as a biomarker to study lesional inflammatory
      events. 

PMID- 23002402
TI  - Transcriptional and secretomic profiling of epidermal cells exposed to alpha
      particle radiation.
AB  - Alpha (alpha)-particle emitters are probable isotopes to be used in a terrorist
      attack. The development of biological assessment tools to identify those who have
      handled these difficult to detect materials would be an asset to our current
      forensic capacity. In this study, for the purposes of biomarker discovery, human
      keratinocytes were exposed to alpha-particle and X-radiation (0.98 Gy/h at 0,
      0.5, 1.0, 1.5 Gy) and assessed for differential gene and protein expression using
      microarray and Bio-Plex technology, respectively. Secretomic analysis of
      supernatants showed expression of two pro-inflammatory cytokines (IL-13 and PDGF
      bb) to be exclusively affected in alpha-particle exposed cells. The highest dose
      of alpha-particle radiation modulated a total of 67 transcripts (fold
      change>|1.5|, (False discovery rate) FDR<0.05) in exposed cells. Several genes
      which responded with high expression levels (>2 fold) included KIF20A, NEFM,
      C7orf10, HIST1H2BD, BMP6, and HIST1H2AC. Among the high expressing genes, five
      (CCNB2, BUB1, NEK2, CDC20, AURKA) were also differentially expressed at the
      medium (1.0 Gy) dose however, these genes were unmodulated following exposure to
      X-irradiation. Networks of these genes clustered around tumor protein-53 and
      transforming growth factor-beta signaling. This study has identified some
      potential gene /protein responses and networks that may be validated further to
      confirm their specificity and potential to be signature biomarkers of alpha
      particle exposure.

PMID- 23002403
TI  - Differences in Clinical Presentation and Findings between Idiopathic Dilated and
      Ischaemic Cardiomyopathy in an Unselected Population of Heart Failure Patients.
AB  - We explored the differences in epidemiologic, clinical, laboratory and
      echocardiographic characteristics between idiopathic dilated (IDCM) and ischaemic
      cardiomyopathy (ICM).Consecutive patients with stable chronic heart failure
      evaluated at a tertiary cardiac centre were enrolled. Clinical examination, blood
      tests and echocardiographic study were performed. A total of 76 patients (43
      IDCM, 33 ICM) were studied. IDCM patients were younger (p<0.001) and female
      gender was more prevalent (p=0.022). NYHA class and left ventricular ejection
      fraction were similar. IDCM patients had lower rates of dyslipidaemia (p<0.001)
      but smoked more than ICM patients (p=0.023) and had higher rates of family
      history of sudden cardiac death (p=0.048). Blood pressure was similar but resting
      heart rate was higher in IDCM patients (p=0.022). IDCM patients presented less
      frequently with peripheral oedema or ascites (p=0.046 and 0.020, respectively)
      and showed better right ventricular function on echocardiogram. QRS duration was
      similar between groups but only in IDCM patients there was a positive correlation
      between QRS duration and age (r=0.619, p<0.001). Cardiac output was similar but
      functional capacity assessed by the Duke Activity Status Index was better in IDCM
      (p=0.036). Despite these differences, IDCM and ICM patients received similar
      treatments. Patients with IDCM were younger, presented lower rates of right
      ventricular dysfunction and clinical right ventricular failure and had better
      functional capacity. Additional differences in clinical and laboratory findings
      exist pointing to a different patient population with diverse prognosis and
      potential need for individualized management.

PMID- 23002404
TI  - Weekend versus weekday, morning versus evening admission in relationship to
      mortality in acute coronary syndrome patients in 6 middle eastern countries:
      results from gulf race 2 registry.
AB  - We used prospective cohort data of patients with acute coronary syndrome (ACS) to
      compare their management on weekdays/mornings with weekends/nights, and the
      possible impact of this on 1-month and 1-year mortality. Analyses were evaluated
      using univariate and multivariate statistics. Of the 4,616 patients admitted to
      hospitals with ACS, 76% were on weekdays. There were no significant differences
      in 1-month (odds ratio (OR), 0.88; 95% CI: 0.68-1.14) and 1-year mortality (OR,
      0.88; 95% CI: 0.70-1.10), respectively, between weekday and weekend admissions.
      Similarly, there were no significant differences in 1-month (OR, 0.92; 95% CI:
      0.73-1.15) and 1-year mortality (OR, 0.98; 95% CI: 0.80-1.20), respectively,
      between nights and day admissions. In conclusion, apart from lower utilization of
      angiography (P < .001) at weekends, there were largely no significant
      discrepancies in the management and care of patients admitted with ACS on
      weekdays and during morning hours compared with patients admitted on weekends and
      night hours, and the overall 30-day and 1-year mortality was similar between both
      the cohorts.

PMID- 23002405
TI  - Differing Relations to Early Atherosclerosis between Vitamin C from Supplements
      vs. Food in the Los Angeles Atherosclerosis Study: A Prospective Cohort Study.
AB  - OBJECTIVE: To determine the relationship of vitamin c intake from supplements vs
      food on early atherosclerosis detected by carotid intima media thickness (IMT).
      BACKGROUND: Oxidative stress and endothelial dysfunction play a critical role in
      the pathogenesis of atherosclerosis. Dietary vitamin C appears to have anti
      oxidant properties and beneficial relations to endothelial function, yet vitamin
      C taken as a vitamin supplement does not appear to protect from cardiovascular
      events. The impact of vitamin c intake from supplements vs food on progression of
      atherosclerosis is unknown. METHODS: We examined 3-year progression of carotid
      IMT in a randomly sampled cohort of 573 healthy women and men aged 40-60 years.
      Progression of carotid IMT was determined bilaterally with B-mode ultrasound at 3
      examinations (1.5-year intervals). Intake of dietary vitamin C was measured by
      six, 24-hour recall interviews. Intake of vitamin C from vitamin supplements was
      measured by questionnaire in quartiles of supplement intake and no supplement.
      Vitamin C wasmeasured in plasma as ascorbic acid. RESULTS: Carotid IMT progressed
      10.0+/-16.5 MUm/year (mean+/-SD) among all those with follow-up (n=500; 87%). For
      those who took vitamin C supplements, carotid IMT progression increased with dose
      (p-trend=0.0009). Among persons in the highest quartile (857-5000 mg/day) of
      vitamin C supplement intake compared to those not consuming any vitamin C
      supplements, carotid IMT progression increased three-fold (20.3+/-2.6 versus
      7.6+/-1.8 MUm/year (mean+/-SD); p<0.001). The adverse association of vitamin C
      supplement intake with carotid IMT was two-fold greater in the upper tertile of
      serum cholesterol compared to the lower two tertiles (p=0.01). In contrast to the
      adverse association of vitamin C supplements, vitamin C intake from food had a
      weak protective relationship on carotid IMT progression (reduced progression 
      5.0+/-1.9 MUm/year; p=0.008). CONCLUSIONS: Vitamin C supplementation is
      associated with accelerated early atherosclerosis measured by carotid IMT
      compared to a protective association with vitamin C from food. Theadverse
      association of vitamin C supplementation may be greater in patients with higher
      serum cholesterol levels. The current results provide a potential mechanistic
      understanding for the observed differences between Vitamin C in supplements vs
      food in prior studies. Given these observations,vitamin C supplementation does
      not appear to be currently advisable for prevention or treatment of
      atherosclerosis.

PMID- 23002406
TI  - Fluoroquinolone resistance among gram-negative urinary tract pathogens: global
      smart program results, 2009-2010.
AB  - OBJECTIVES: To determine the rates of fluoroquinolone resistant (FQR) in gram
      negative bacilli urinary tract infections (UTIs) in a global population. METHODS:
      The Study for Monitoring Antimicrobial Resistance Trends (SMART) collected 1,116
      FQR gram-negative urinary pathogens from hospitalized patients in 33 countries
      during 2009-2010. Amikacin, ertapenem, and imipenem were the most active agents
      tested against FQR UTI pathogens, including extended-spectrum beta-lactamase
      producers. RESULTS: FQR rates vary widely country to country with a range of 6%
      to 75%. Regional FQR rates were 23.5% in North America, 29.4% in Europe, 33.2% in
      Asia, 38.7% in Latin America, and 25.5% in the South Pacific. CONCLUSIONS: These
      observations suggest that fluoroquinolones may no longer be effective as first
      line therapy for gram-negative UTI in hospitalized patients.

PMID- 23002407
TI  - At Odds: Concerns Raised by Using Odds Ratios for Continuous or Common
      Dichotomous Outcomes in Research on Physical Activity and Obesity.
AB  - PURPOSE: Research on obesity and the built environment has often featured
      logistic regression and the corresponding parameter, the odds ratio. Use of odds
      ratios for common outcomes such obesity may unnecessarily hinder the validity,
      interpretation, and communication of research findings.  METHODS: We identified
      three key issues raised by the use of odds ratios, illustrating them with data on
      walkability and body mass index from a study of 13,102 New York City residents. 
      RESULTS: First, dichotomization of continuous measures such as body mass index
      discards theoretically relevant information, reduces statistical power, and
      amplifies measurement error. Second, odds ratios are systematically higher
      (further from the null) than prevalence ratios; this inflation is trivial for
      rare outcomes, but substantial for common outcomes like obesity. Third, odds
      ratios can lead to incorrect conclusions during tests of interactions. The odds
      ratio in a particular subgroup might higher simply because the outcome is more
      common (and the odds ratio inflated) compared with other subgroups.  CONCLUSION:
      Our recommendations are to take full advantage of continuous outcome data when
      feasible and to use prevalence ratios in place of odds ratios for common
      dichotomous outcomes. When odds ratios must be used, authors should document
      outcome prevalence across exposure groups.

PMID- 23002408
TI  - Signal transduction pathways in chronic inflammatory rheumatic diseases.

PMID- 23002410
TI  - Rituximab (RTX) as an Alternative to TNF-Alpha Antagonists in Patients with
      Rheumatoid Arthritis and High Risk of Severe Infections: A Systematic Analysis of
      the Experience in One Center.
AB  - OBJECTIVES: The use of TNF-alpha antagonists may be associated with an increased
      rate of infections in risk populations of patients with RA. Our hypothesis was
      that in patients with a high risk of infection Rituximab (RTX) could be a safer
      alternative. METHODS: We analyzed the outcome of RA patients who received RTX
      instead of TNF-alpha antagonist because of a history of serious infections or
      frequent infectious events. All patients in a given time period were included in
      the retrospective analysis. RESULTS: 32 patients were identified according to the
      above criteria and followedup for a mean period of 16 +/- 8 months (range 6 - 36)
      during treatment with RTX. Only one patient was lost to follow-up. Sixteen
      patients were anti-TNF-naive and in the remaining patients the TNF-alpha
      antagonist was stopped due to infectious complications before starting RTX. RTX
      was combined with a disease modifying drug in 22 (69%) of the cases. Altogether 4
      severe infections occurred (9.5/100 patient years), mainly within the first year
      of treatment with RTX. Two patients suffered from pneumonia, 1 from a
      postoperative wound infection, 1 from an ear abscess and bacterial bronchitis.
      None of our patients with a previous history of bacterial infections of soft
      tissue, bacterial arthritis or osteomyelitis (n=9) developed recurrent infection.
      No relapse of a previously diagnosed tuberculosis (n=9) was seen. CONCLUSIONS: In
      this particular high risk population of RA patients, treatment with RTX seems to
      be an alternative to TNF-alpha-antagonist and has a relatively low rate of
      recurrent infection.

PMID- 23002409
TI  - Personality and fibromyalgia syndrome.
AB  - OBJECTIVES: We aimed to review how personality characteristics contribute to the
      onset, maintenance or modulation of fibromyalgia. METHOD: The databases Medline
      and PsychINFO were examined from 1967 to 2012 to identify studies that
      investigated associations between fibromyalgia and personality. Search terms
      included fibromyalgia and personality, trait psychology, characteristics and
      individual differences. RESULTS: Numerous studies indicate that patients with
      fibromyalgia experience psychological distress. Various instruments have been
      used to evaluate distress and related psychological domains, such as anxiety or
      depression, in fibromyalgia. In many cases, these same instruments have been used
      to study personality characteristics in fibromyalgia with a subsequent blurring
      of cause and effect between personality and psychological distress. In addition,
      the symptoms of fibromyalgia may change pre-illness personality characteristics
      themselves. These issues make it difficult to identify specific personality
      characteristics that might influence the fibromyalgia process. Despite this
      inherent problem with the methodologies used in the studies that make up this
      literature review, or perhaps because of it, we found no defined personality
      profile specific to fibromyalgia. However, many patients with fibromyalgia do
      show personality characteristics that facilitate psychological responses to
      stressful situations, such as catastrophising or poor coping techniques, and
      these in turn associate with mechanisms contributing to fibromyalgia. CONCLUSION:
      No specific fibromyalgia personality is defined but it is proposed that
      personality is an important filter that modulates a person's response to
      psychological stressors. Certain personalities may facilitate translation of
      these stressors to physiological responses driving the fibromyalgia mechanism.

PMID- 23002411
TI  - Synergistic Effect of TGF-beta1 And BMP-7 on Chondrogenesis and Extracellular
      Matrix Synthesis: An In Vitro Study.
AB  - INTRODUCTION: The purpose of the present study seeks to determine the signal
      timing of BMP-7 and TGF-beta1 from a novel chitosan based hydrogel system that
      may affect chondrocyte proliferation resulting in the presence of a synergism
      seen conspicuously in consecutive controlled delivery. METHODS: Four groups of
      cultured chondrocytes were seeded on a novel designed chitosan based hydrogel.
      The hydrogel was left empty (control) in one group and loaded with BMP-7, TGF
      beta1 and their combination in the other groups, respectively. Hydrogel structure
      was analyzed with scanning electron microscope. The release kinetics of Growth
      Factors (GFs) was determined with ELISA. Chondrocyte viability and toxicity after
      being tested with MTS and collagen type II synthesis, were quantified with
      western blotting. Canonical regression analysis was used for measuring
      statistical evaluation. RESULTS: Chitosan based hydrogel allowed controlled
      release of GFs in different time intervals for BMP-7 and TGF-beta1. Double peak
      concentration gradient was found to be present in the group loaded with both GFs.
      In this group, substantially higher chondrocyte growth and collagen synthesis
      were also detected. CONCLUSIONS: We concluded that, chitosan based hydrogel
      systems may be adjusted to release GFs consecutively during biodegradation at the
      layers of surface, which may increase the cell number and enhance collagen type
      II synthesis.

PMID- 23002412
TI  - Secondary Patellar Resurfacing after Primary Bicondylar Knee Arthroplasty did Not
      Meet Patients' Expectations.
AB  - Secondary patella resurfacing is a controversial procedure which is applied in
      patients with anterior knee pain after a bicondylar knee arthroplasty (with
      unresurfaced patella). A group of 46 patients were submitted to this procedure
      and their satisfaction, range of motion and pain improvement was evaluated. 52.2%
      of the patients were satisfied with the procedure, with an improvement in pain
      (Visual Analogue Scale) of 65% and an improvement in range of motion in 56,5%,
      with roundabout half of the patients having no resolution to their complaints.
      Whilst an improvement was not achieved in all patients, as it was initially
      hypothesised, this procedure should be considered when a revision knee
      arthroplasty is performed with an unresurfaced patella.

PMID- 23002413
TI  - Multifragmentary tibial pilon fractures: midterm results after osteosynthesis
      with external fixation and multiple lag screws.
AB  - Osteosynthesis of intraarticular tibial pilon fractures is preferably achieved
      using locking plates via a minimally invasive technique. If combined with severe
      soft tissue damage there is a high risk of wound-healing deficits after plate
      osteosynthesis. Thus our aim was to find an alternative method of treatment for
      those cases with combined soft tissue injuries.We report on five cases with
      comminuted fractures of the joint surface combined with critical soft tissue
      condition that were treated with lag screws and external fixation (AO) applied
      across the ankle joint. All five patients were followed up, undergoing clinical
      and radiological examination.Using this approach we achieved fracture healing of
      comminuted fractures without further complications. Clinical follow-up after an
      average of 55.6 (36-75) months revealed a mean AOFAS score of 81 (62-100).We
      therefore propose combined treatment using lag screws with external fixation as a
      practical treatment option for those fractures for which lag screws combined with
      a locking plate are not feasible or when there is a high risk of wound-healing
      deficits due to severe soft tissue damage.

PMID- 23002414
TI  - The incidence of retinal detachment after cataract surgery.
AB  - PURPOSE: To estimate the cumulative risk of retinal detachment (RD) after routine
      cataract surgery by phacoemulsification. SETTING: Department of Ophthalmology,
      Aarhus University Hospital, Denmark METHODS: Retrospective cohort study based on
      12.222 consecutive cataract surgeries in 7.856 patients using phacoemulsification
      over a 6 year period from 2000 to 2005. Cases with a diagnosis of RD were
      identified through the procedure-coding database at the Medical Registry of
      Aarhus University Hospital, which is based on Diagnosis Related Groups (DRG) and
      used to report to the Danish Patients Registry (LPR). For each case the age of
      the patient, gender, axial length, surgical complications, postoperative Nd:YAG
      capsulotomy and time interval between cataract surgery and RD were recorded.
      RESULTS: The mean follow-up time was 64.8 months (range 26.2-97.6 months). Forty
      eight (48) cases of RD were identified making an overall cumulative risk of
      0.39%. As compared to the normal incidence of RD reported in the Scandinavian
      literature, the relative risk of RD following cataract surgery was about 2.3
      times that of the natural incidence. As compared to the average cataract group,
      the group of RD following cataract surgery was characterized by a younger mean
      age (60.5 vs. 73.7 years), male gender (58.3% vs 34.8%), longer axial lengths
      (24.56 vs 23.25 mm) and a higher frequency of surgical complications (10.4% vs
      1.8%) (p<0.001) but not a higher frequency of Nd:YAG capsulotomy (p>0.05),
      CONCLUSIONS: The cumulative risk of RD after lens surgery was about 2.3 times the
      natural incidence but seems to be lower than that of older reports. SYNOPSIS:
      Retinal detachment following cataract surgery is associated with young age, male
      gender, long axial lengths and surgical complications. The cumulative risk of RD
      after lens surgery was about 2.3 times the natural.

PMID- 23002415
TI  - Clinical and molecular features associated with cystic visceral lesions in von
      hippel-lindau disease.
AB  - BACKGROUND: Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which
      occurs as a result of genetic mutations on chromosome 3p. Retinal capillary
      haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic
      phenotypic analyses, but cystic visceral lesions are less common and have been
      less frequently studied. The aim of this study was to perform genotypic and
      phenotypic analysis of a cohort of VHL patients that developed cystic visceral
      lesions to determine whether their genotype differs from that seen in other
      manifestations of VHL and whether the ocular manifestations differ. METHODS: This
      study reports a prospective case series of twenty-one patients identified from
      the Hammersmith Hospital Genetics Service database as having VHL mutations.
      Patients underwent regular ocular and systemic screening as well as genotypic
      analysis. The main outcome measures were the development of VHL lesions, either
      ocular or systemic. RESULTS: Cystic visceral lesions were detected in six of the
      21 patients from the clinic (29%). These included renal cysts in four patients,
      pancreatic cysts in three patients, and an epididymal cystadenoma in one patient.
      Renal cysts were not associated with any specific genotype. Pancreatic cysts
      appeared to occur in association with VHL gene deletions and all developed CNS
      haemangioblastomas. Only one patient developed ocular manifestations, which
      occurred in this patient in the form of two retinal capillary haemangiomas.
      CONCLUSIONS: VHL gene deletions appeared to be associated with pancreatic cysts
      and the development of CNS haemangioblastomas. Ocular manifestations are uncommon
      in this group of patients.

PMID- 23002416
TI  - Imaging Tests, Provocative Tests, Including Exercise Testing in Women with
      Suspected Coronary Artery Disease.
AB  - Evolving knowledge regarding sex differences in coronary heart disease has
      demonstrated that the prevalence, symptomatology, and pathophysiology of coronary
      atherosclerosis vary between genders. Women experience higher mortality rates and
      more adverse outcomes after acute myocardial infarction than men, despite a lower
      prevalence of obstructive coronary artery disease. Based on recent insights into
      the complex pathophysiology of coronary heart disease which includes a spectrum
      of obstructive coronary artery disease and dysfunction of the coronary
      microvasculature and endothelium, the term ischemic heart disease is a more
      accurate term for discussion of coronary atherosclerosis specific to women. In
      women, with clinical features and risk factors for ischemic heart disease, the
      detection and evaluation of ischemic heart disease is challenging due to the
      diverse pathogenic mechanisms of ischemic heart diseases in women. In this
      article, we discuss noninvasive imaging tests, provocative tests, including
      exercise testing in women with suspected ischemic heart disease.

PMID- 23002417
TI  - Maternal Obesity and the Fetal Origins of the Metabolic Syndrome.
AB  - Over recent decades there has been a rapid rise in metabolic disorders throughout
      the world. Whilst lifestyle and societal habits have contributed to the obesity
      epidemic, there is now increasing evidence that the early developmental
      environment of an infant can play a pivotal role in the 'programming' of an
      adverse physiological phenotype in later life. Clinical evidence highlights that
      maternal over-nutrition and/or obesity during pregnancy presents not only adverse
      effects on maternal health, but also persistent and deleterious effects in the
      developing child. Animal models are providing essential information into the
      underlying cellular and molecular mechanisms that contribute to this adverse
      phenotype. The use of this information will aid our understanding of the
      programming signals related to maternal and paternal over-nutrition and the
      improved healthcare for both mother and infant.

PMID- 23002418
TI  - Investigating Cognitive Pathways to Psychopathology: Predicting Depression and
      Posttraumatic Stress Disorder From Early Responses After Assault.
AB  - Depression and posttraumatic stress disorder (PTSD) are common after trauma, but
      it remains unclear what factors determine which disorder a trauma survivor will
      develop. A prospective longitudinal study of 222 assault survivors assessed
      candidate predictors derived from cognitive models of depression and PTSD at 2
      weeks posttrauma (N = 222), and depression and PTSD symptom severities (N = 183,
      82%) and diagnoses at 6 months (N = 205, 92%). Structural equation modeling
      showed that the depression and PTSD models predicted both depression and PTSD
      symptom severity, but that the disorder-specific models predicted the respective
      outcome best (43% for depression, 59% for PTSD symptom severity). Maintaining
      cognitive variables (hopelessness and self-devaluative thoughts in depression;
      cognitive responses to intrusive memories and persistent dissociation in PTSD)
      showed the clearest specific relationships with outcome. Model-derived variables
      predicted depression and PTSD diagnoses at 6 months over and above what could be
      predicted from initial diagnoses. Results support the role of cognitive factors
      in the development of depression and PTSD after trauma, and provide preliminary
      evidence for some specificity in maintaining cognitive mechanisms.

PMID- 23002419
TI  - From in Silico Discovery to intra-Cellular Activity: Targeting JNK-Protein
      Interactions with Small Molecules.
AB  - The JNK-JIP1 interaction represents an attractive target for the selective
      inhibition of JNK-mediated signaling. We report a virtual screening (VS)
      workflow, based on a combination of three-dimensional shape and electrostatic
      similarity to discover novel scaffolds for the development of non-ATP competitive
      inhibitors of JNK targeting the JNK-JIP interaction. Of 352 (0.13%) compounds
      selected from the NCI diversity set more than 22% registered as hits in a
      biochemical kinase assay. Several compounds discovered to inhibit JNK activity
      under standard kinase assay conditions also impeded JNK activity in HEK293 cells.
      These studies led to the discovery that the lignan (-)-zuonin A inhibits JNK
      protein interactions with a selectivity of 100-fold over ERK2 and p38 MAPKalpha.
      These results demonstrate the utility of a virtual screening protocol to identify
      novel scaffolds for highly selective, cell-permeable inhibitors of JNK-protein
      interactions.

PMID- 23002420
TI  - Nanopore-Based Sensors for Detecting Toxicity of a Carbon Nanotube to Proteins.
AB  - A carbon nanotube (CNT) can be toxic to a living cell by binding to proteins and
      then impairing their functionalities; however, an efficient screening method that
      examines binding capability of a CNT to protein molecules in vitro is still
      unavailable. Here, we show that a nanopore-based sensor can be used to
      investigate CNT-protein interactions. With proof-of-principle molecular dynamics
      simulations, we have measured ionic currents in a nanopore when threading a CNT
      protein complex through the pore, and demonstrated that CNT's binding capability,
      and thus potential nanotoxicity, can be inferred from current signals. We have
      then further investigated mechanics and energetics of CNT-protein interactions
      with the nanopore sensor. These findings indicate that solid-state nanopores have
      the potential to be ultra-sensitive and high-throughput sensors for nanotoxicity.

PMID- 23002421
TI  - Purification and characterization of a novel secondary fimbrial protein from
      Porphyromonas gulae.
AB  - BACKGROUND: Porphyromonas gulae are black-pigmented anaerobic bacteria isolated
      from the gingival sulcus of various animal hosts and are distinct from
      Porphyromonas gingivalis originating in humans. We previously reported the
      antigenic similarities of 41-kDa fimbriae between P. gulae ATCC 51700 and P.
      gingivalis ATCC 33277. In this study, to clarify the presence of another type of
      fimbriae of P. gulae, we have purified and characterized the secondary fimbrial
      protein from P. gulae ATCC 51700. METHODS: The secondary fimbrial protein was
      purified from P. gulae ATCC 51700 using an immunoaffinity column coupling with
      antibodies against the 41-kDa fimbrial protein. The expression of fimbriae on the
      cell surface of P. gulae ATCC 51700 was investigated by transmission electron
      microscopy. The N-terminal amino acid sequence was determined by an amino acid
      sequencer system. RESULTS: The molecular mass of this protein was approximately
      53-kDa, as estimated by SDS-PAGE. The polyclonal antibodies against the 53-kDa
      protein did not react with the 41-kDa fimbrial protein of P. gulae ATCC 51700.
      Immunogold electron microscopy revealed that anti-53-kDa fimbrial serum bound to
      fimbria on the cell surface of P. gulae ATCC 51700. The amino acid sequence of
      the N-terminal 15 residues of the 53-kDa fimbrial protein showed only 1 of 15
      residues identical to the 41-kDa fimbrial protein. CONCLUSION: The 53-kDa
      fimbriae are different in molecular weight and antigenicity from the 41-kDa
      fimbrial protein of P. gulae ATCC 51700. These results clearly suggest that the
      41-kDa and the 53-kDa fimbriae are distinct types of fimbriae expressed
      simultaneously by this organism.

PMID- 23002423
TI  - Large-area high-throughput synthesis of monolayer graphene sheet by Hot Filament
      Thermal Chemical Vapor Deposition.
AB  - We report hot filament thermal CVD (HFTCVD) as a new hybrid of hot filament and
      thermal CVD and demonstrate its feasibility by producing high quality large area
      strictly monolayer graphene films on Cu substrates. Gradient in gas composition
      and flow rate that arises due to smart placement of the substrate inside the Ta
      filament wound alumina tube accompanied by radical formation on Ta due to
      precracking coupled with substrate mediated physicochemical processes like
      diffusion, polymerization etc., led to graphene growth. We further confirmed our
      mechanistic hypothesis by depositing graphene on Ni and SiO(2)/Si substrates.
      HFTCVD can be further extended to dope graphene with various heteroatoms (H, N,
      and B, etc.,), combine with functional materials (diamond, carbon nanotubes
      etc.,) and can be extended to all other materials (Si, SiO(2), SiC etc.,) and
      processes (initiator polymerization, TFT processing) possible by HFCVD and
      thermal CVD.

PMID- 23002422
TI  - Large-scale identification of target proteins of a glycosyltransferase isozyme by
      Lectin-IGOT-LC/MS, an LC/MS-based glycoproteomic approach.
AB  - Model organisms containing deletion or mutation in a glycosyltransferase-gene
      exhibit various physiological abnormalities, suggesting that specific glycan
      motifs on certain proteins play important roles in vivo. Identification of the
      target proteins of glycosyltransferase isozymes is the key to understand the
      roles of glycans. Here, we demonstrated the proteome-scale identification of the
      target proteins specific for a glycosyltransferase isozyme, beta1,4
      galactosyltransferase-I (beta4GalT-I). Although beta4GalT-I is the most
      characterized glycosyltransferase, its distinctive contribution to beta1,4
      galactosylation has been hardly described so far. We identified a large number of
      candidates for the target proteins specific to beta4GalT-I by comparative
      analysis of beta4GalT-I-deleted and wild-type mice using the LC/MS-based
      technique with the isotope-coded glycosylation site-specific tagging (IGOT) of
      lectin-captured N-glycopeptides. Our approach to identify the target proteins in
      a proteome-scale offers common features and trends in the target proteins, which
      facilitate understanding of the mechanism that controls assembly of a particular
      glycan motif on specific proteins.

PMID- 23002424
TI  - Hierarchical nested wrinkles on silica-polymer hybrid films: stimuli-responsive
      micro periodic surface architectures.
AB  - Stimuli-response on hierarchically-structured surface wrinkles is required for
      advanced filtration, catalysis and sensing applications. Although conventional
      processes can form hierarchical surface wrinkles, incorporation of stimuli
      responsive features has not been achieved, limiting the potential multi-scale
      functionality of wrinkles. Here, we demonstrate a novel process that can
      fabricate stimuli-responsive surface hierarchical structures on silica-polymer
      hybrid films through precisely controlled UV-polymerization and sol-gel
      condensation. Starting from uniform hybrid films, UV excitation of the film
      surface triggers the formation of micrometre-scale wrinkles with dual
      periodicity. Hierarchical nested wrinkle (NW) structures with controllable
      periodic lengths at discrete size scales of < 10 um and > 23 um show a shape
      memory effect with changes in the surrounding humidity. Moreover, the individual
      responses of wrinkles with different periodicities can be controlled
      independently. As a proof-of-concept application, we demonstrate that the NW
      structures are an active size-selective adsorption/release surface for micrometre
      sized particles.

PMID- 23002425
TI  - PEG-labeled nucleotides and nanopore detection for single molecule DNA sequencing
      by synthesis.
AB  - We describe a novel single molecule nanopore-based sequencing by synthesis (Nano
      SBS) strategy that can accurately distinguish four bases by detecting 4 different
      sized tags released from 5'-phosphate-modified nucleotides. The basic principle
      is as follows. As each nucleotide is incorporated into the growing DNA strand
      during the polymerase reaction, its tag is released and enters a nanopore in
      release order. This produces a unique ionic current blockade signature due to the
      tag's distinct chemical structure, thereby determining DNA sequence
      electronically at single molecule level with single base resolution. As proof of
      principle, we attached four different length PEG-coumarin tags to the terminal
      phosphate of 2'-deoxyguanosine-5'-tetraphosphate. We demonstrate efficient,
      accurate incorporation of the nucleotide analogs during the polymerase reaction,
      and excellent discrimination among the four tags based on nanopore ionic
      currents. This approach coupled with polymerase attached to the nanopores in an
      array format should yield a single-molecule electronic Nano-SBS platform.

PMID- 23002426
TI  - A clinical approach to neuraxial morphine for the treatment of postoperative
      pain.
AB  - Opioids are considered a "gold standard" in clinical practice for the treatment
      of postoperative pain. The spinal administration of an opioid drug does not
      guarantee selective action and segmental analgesia in the spine. Evidence from
      experimental studies in animals indicates that bioavailability in the spinal cord
      biophase is negatively correlated with liposolubility, and is higher for
      hydrophilic opioids, such as morphine, than lipophilic opioids, such as fentanyl,
      sufentanil and alfentanil. Epidural morphine sulphate has proven analgesic
      efficacy and superiority over systemically administered morphine for improving
      postoperative pain. However, pain relief after a single epidural injection of
      morphine could last less than 24 hours. Techniques used to administered and
      prolong opioid epidural analgesia, can be costly and inconvenient. Moreover,
      complications can arise from indwelling epidural catheterization, particularly in
      patients receiving anticoagulants. Clinical trials have shown that epidural
      morphine in the form of extended-release liposome injections (EREM) gives good
      analgesia for a period of 48 hours, with no need for epidural catheterisation.
      Intrathecal morphine produces intense analgesia for up to 24 hours with a single
      shot, and clinical recommendation is to choose the minimum effective dose and do
      not exceed 300 MUg to prevent the delay respiratory depression.

PMID- 23002427
TI  - Phimosis in children.
AB  - Phimosis is nonretraction of prepuce. It is normally seen in younger children due
      to adhesions between prepuce and glans penis. It is termed pathologic when
      nonretractability is associated with local or urinary complaints attributed to
      the phimotic prepuce. Physicians still have the trouble to distinguish between
      these two types of phimosis. This ignorance leads to undue parental anxiety and
      wrong referrals to urologists. Circumcision was the mainstay of treatment for
      pathologic phimosis. With advent of newer effective and safe medical and
      conservative surgical techniques, circumcision is gradually getting outmoded.
      Parents and doctors should a be made aware of the noninvasive options for
      pathologic phimosis for better outcomes with minimal or no side-effects. Also
      differentiating features between physiologic and pathologic phimosis should be
      part of medical curriculum to minimise erroneous referrals for surgery.

PMID- 23002428
TI  - Antibody-Mediated Lung Transplant Rejection.
AB  - Antibody-mediated rejection after lung transplantation remains enigmatic.
      However, emerging evidence over the past several years suggests that humoral
      immunity plays an important role in allograft rejection. Indeed, the development
      of donor-specific antibodies after transplantation has been identified as an
      independent risk factor for acute cellular rejection and bronchiolitis obliterans
      syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in
      severe allograft dysfunction have been reported, and these demonstrate that
      antibodies can directly injure the allograft. However, the incidence and toll of
      antibody-mediated rejection are unknown because there is no widely accepted
      definition and some cases may be unrecognized. Clearly, humoral immunity has
      become an important area for research and clinical investigation.

PMID- 23002429
TI  - MDM2 and MDMX: Alone and together in regulation of p53.
AB  - p53, a critical tumor suppressor, is activated by various cellular stresses to
      prevent and repair damages that can lead to tumor development. In response to
      these stresses, p53 activation can cause very serious cellular effects including
      permanent cell cycle arrest and cell death. p53 must therefore be very tightly
      regulated to avoid unnecessary pathological effects. The homologs MDM2 and MDMX
      have been shown to be the major, essential negative regulators of p53. In normal
      cells, MDM2 and MDMX suppress p53 activity, but in the event of cellular stress,
      they themselves must be inhibited so that p53 may respond to the stress. MDM2 and
      MDMX are known to bind together, and play multifaceted, non-redundant roles in
      modulating p53 protein activity. Recently, evidence has emerged showing that MDM2
      and MDMX most effectively inhibit p53 as a complex, and possibly play non
      redundant roles because they must function as one to control p53. In this review,
      we give an overview of MDM2 and MDMX and discuss a few ways in which they are
      modified so that p53 may be activated. Lastly, we discuss the non-redundant roles
      of MDM2 and MDMX and how it is important to investigate the effect on the complex
      as a whole when investigating either protein.

PMID- 23002430
TI  - Small RNA and its application in andrology and urology.
AB  - Small non-coding RNAs such as small interfering RNA (siRNA), microRNA (miRNA) and
      piwi-interacting RNA (piRNA) exist in almost all kingdoms of organisms and have
      recently emerged as master regulators of gene expression to affect a diverse
      range of important biological processes. They exert their functions largely
      through two related but opposing mechanisms: RNA interference (RNAi) mediated by
      siRNA, miRNA and piRNA, and RNA activation (RNAa) mediated by small activating
      RNA (saRNA) and miRNA, leading to silencing and overexpression of target genes
      respectively. Dysregulation of these mechanisms have been implicated in a variety
      of human diseases including urological and andrological diseases. Importantly,
      both mechanisms can be readily harnessed for therapeutic purposes for a variety
      of diseases by using small RNA molecules as the "ribodrug". In this review, we
      highlight recent advances in the applications of small RNA as therapeutics for
      urological cancer, male infertile and erectile dysfunction.

PMID- 23002432
TI  - An epidemic of chronic kidney disease in Central America: an overview.

PMID- 23002431
TI  - Cholangiocarcinoma pathogenesis: Role of the tumor microenvironment.
AB  - Cholangiocarcinoma is a tumor that originates from the neoplastic transformation
      of the epithelial cells of the intrahepatic or extrahepatic bile ducts. This type
      of cancer is difficult to diagnose, extremely aggressive, and has very poor
      prognosis. It is also relatively resistant to chemotherapy and radiation therapy.
      Its pathogenesis is poorly understood, however it is known that the tumor
      microenvironment is a very important factor in the regulation of tumor
      angiogenesis, invasion, and metastasis. The current knowledge about the
      mechanisms by which these events are regulated as well as the role of the tumor
      microenvironment in the pathogenesis and classification of cholangiocarcinoma
      will be discussed.

PMID- 23002433
TI  - The role and status of evidence and innovation in the healthy towns programme in
      England: a qualitative stakeholder interview study.
AB  - BACKGROUND: In 2008, the Healthy Community Challenge Fund commissioned nine
      'healthy towns' in England to implement and evaluate community-based
      environmental interventions to prevent obesity. This paper examines the role of
      evidence in informing intervention development, innovation and the potential for
      programmes to contribute to the evidence base on the effectiveness of
      interventions that tackle population obesity. METHOD: Twenty qualitative
      interviews with local programme stakeholders and national policy actors were
      conducted. Interview transcripts were coded and thematically analysed. Initial
      analyses were guided by research questions regarding the nature and role of
      evidence in the development and implementation of the healthy towns programme and
      the capacity for evidence generation to inform future intervention design, policy
      and practice. FINDINGS: Stakeholders relied on local anecdotal and observational
      evidence to guide programme development. While the programme was considered an
      opportunity to trial new and innovative approaches, the requirement to predict
      likely health impacts and adopt evidence-based practice was viewed contradictory
      to this aim. Stakeholders believed there were missed opportunities to add to the
      existing empirical evidence base due to a lack of clarity and planning,
      particularly around timing, in local and national evaluations. CONCLUSIONS: A
      strong emphasis on relying on existing evidence-based practice and producing
      positive impacts and outcomes may have impeded the opportunity to implement truly
      innovative programmes because of fear of failure. Building more time for
      development, implementation and evaluation into future initiatives would maximise
      the use and generation of robust and relevant evidence for public health policy
      and practice.

PMID- 23002434
TI  - PIN2 is required for the adaptation of Arabidopsis roots to alkaline stress by
      modulating proton secretion.
AB  - Soil alkalinity is a widespread environmental problem that limits agricultural
      productivity. The hypothesis that an auxin-regulated proton secretion by plasma
      membrane H(+)-ATPase plays an important role in root adaption to alkaline stress
      was studied. It was found that alkaline stress increased auxin transport and PIN2
      (an auxin efflux transporter) abundance in the root tip of wild-type Arabidopsis
      plants (WT). Compared with WT roots, the pin2 mutant roots exhibited much reduced
      plasma membrane H(+)-ATPase activity, root elongation, auxin transport, and
      proton secretion under alkaline stress. More importantly, roots of the pks5
      mutant (PKS5, a protein kinase) lacking PIN2 (a pks5/pin2 double mutant) lost the
      previous higher proton-secretion capacity and higher elongation rate of primary
      roots under alkaline stress. By using Arabidopsis natural accessions with a high
      proton-secretion capacity, it was found that their PIN2 transcription abundance
      is positively related to the elongation rate of the primary root and proton
      secretion capacity under alkaline stress. Taken together, our results confirm
      that PIN2 is involved in the PKS5-mediated signalling cascade under alkaline
      stress and suggest that PIN2 is required for the adaptation of roots to alkaline
      stress by modulating proton secretion in the root tip to maintain primary root
      elongation.

PMID- 23002435
TI  - Exposure to ionizing radiation induces the migration of cutaneous dendritic cells
      by a CCR7-dependent mechanism.
AB  - In the event of a deliberate or accidental radiological emergency, the skin would
      likely receive substantial ionizing radiation (IR) poisoning, which could
      negatively impact cellular proliferation, communication, and immune regulation
      within the cutaneous microenvironment. Indeed, as we have previously shown, local
      IR exposure to the murine ear causes a reduction of two types of cutaneous
      dendritic cells (cDC), including interstitial dendritic cells of the dermis and
      Langerhans cells of the epidermis, in a dose- and time-dependent manner. These
      APCs are critical regulators of skin homeostasis, immunosurveillance, and the
      induction of T and B cell-mediated immunity, as previously demonstrated using
      conditional cDC knockout mice. To mimic a radiological emergency, we developed a
      murine model of sublethal total body irradiation (TBI). Our data would suggest
      that TBI results in the reduction of cDC from the murine ear that was not due to
      a systemic response to IR, as a loss was not observed in shielded ears. We
      further determined that this reduction was due, in part, to the upregulation of
      the chemoattractant CCL21 on lymphatic vessels as well as CCR7 expressed on cDC.
      Migration as a potential mechanism was confirmed using CCR7(-/-) mice in which
      cDC were not depleted following TBI. Finally, we demonstrated that the loss of
      cDC following TBI results in an impaired contact hypersensitivity response to
      hapten by using a modified contact hypersensitivity protocol. Taken together,
      these data suggest that IR exposure may result in diminished immunosurveillance
      in the skin, which could render the host more susceptible to pathogens.

PMID- 23002436
TI  - The TLR7/8 agonist CL097 primes N-formyl-methionyl-leucyl-phenylalanine
      stimulated NADPH oxidase activation in human neutrophils: critical role of
      p47phox phosphorylation and the proline isomerase Pin1.
AB  - Superoxide anion production by the neutrophil NADPH oxidase plays a key role in
      host defense; however, excessive superoxide production is believed to participate
      to inflammatory reactions. Neutrophils express several TLR that recognize a
      variety of microbial motifs or agonists. The interaction between TLR and their
      agonists is believed to help neutrophils to recognize and eliminate the pathogen.
      However, the effects of some TLR agonists on the NADPH oxidase activation and the
      mechanisms controlling these effects have not been elucidated. In this study, we
      show that the TLR7/8 agonist CL097 by itself did not induce NADPH oxidase
      activation in human neutrophils, but induced a dramatic increase of fMLF
      stimulated activation. Interestingly, CL097 induced cytochrome b558 translocation
      to the plasma membrane and the phosphorylation of the NADPH oxidase cytosolic
      component p47phox on Ser(345), Ser(328), and Ser(315). Phosphorylation of
      Ser(328) and Ser(315) was significantly increased in CL097-primed and fMLF
      stimulated neutrophils. Phosphorylation of Ser(345), Ser(328), and Ser(315) was
      decreased by inhibitors of p38 MAPK and the ERK1/2 pathway. Phosphorylation of
      Ser(328) was decreased by a protein kinase C inhibitor. Genistein, a broad-range
      protein tyrosine kinase inhibitor, inhibited the phosphorylation of these
      serines. Our results also show that CL097 induced proline isomerase 1 (Pin1)
      activation and that juglone, a Pin1 inhibitor, inhibited CL097-mediated priming
      of fMLF-induced p47phox phosphorylation and superoxide production. These results
      show that the TLR7/8 agonist CL097 induces hyperactivation of the NADPH oxidase
      by stimulating the phosphorylation of p47phox on selective sites in human
      neutrophils and suggest that p38 MAPK, ERK1/2, protein kinase C, and Pin1 control
      this process.

PMID- 23002437
TI  - Inducible renitence limits Listeria monocytogenes escape from vacuoles in
      macrophages.
AB  - Membranes of endolysosomal compartments in macrophages are often damaged by
      physical or chemical effects of particles ingested through phagocytosis or by
      toxins secreted by intracellular pathogens. This study identified a novel
      inducible activity in macrophages that increases resistance of phagosomes, late
      endosomes, and lysosomes to membrane damage. Pretreatment of murine macrophages
      with LPS, peptidoglycan, TNF-alpha, or IFN-gamma conferred protection against
      subsequent damage to intracellular membranes caused by photooxidative chemistries
      or by phagocytosis of ground silica or silica microspheres. Phagolysosome damage
      was partially dependent on reactive oxygen species but was independent of the
      phagocyte oxidase. IFN-gamma-stimulated macrophages from mice lacking the
      phagocyte oxidase inhibited escape from vacuoles by the intracellular pathogen
      Listeria monocytogenes, which suggested a role for this inducible renitence
      (resistance to pressure) in macrophage resistance to infection by pathogens that
      damage intracellular membranes. Renitence and inhibition of L. monocytogenes
      escape were partially attributable to heat shock protein-70. Thus, renitence is a
      novel, inducible activity of macrophages that maintains or restores the integrity
      of endolysosomal membranes.

PMID- 23002438
TI  - Cysteinyl leukotriene 2 receptor on dendritic cells negatively regulates ligand
      dependent allergic pulmonary inflammation.
AB  - Cysteinyl leukotrienes (cys-LTs) can mediate Th2 immunity to the house dust mite,
      Dermatophagoides farinae, via the type 1 receptor CysLT(1)R on dendritic cells
      (DCs). However, the role of the homologous type 2 receptor CysLT(2)R in Th2
      immunity is unknown. D. farinae sensitization and challenge of CysLT(2)R
      deficient mice showed a marked augmentation of eosinophilic pulmonary
      inflammation, serum IgE, and Th2 cytokines. Wild-type (WT) mice sensitized by
      adoptive transfer of D. farinae-pulsed CysLT(2)R-deficient bone marrow-derived
      DCs (BMDCs) also had a marked increase in D. farinae-elicited eosinophilic lung
      inflammation and Th2 cytokines in restimulated hilar nodes. This response was
      absent in mice sensitized with D. farinae-pulsed BMDCs lacking leukotriene C(4)
      synthase (LTC(4)S), CysLT(1)R, or both CysLT(2)R/LTC(4)S, suggesting that
      CysLT(2)R negatively regulates LTC(4)S- and CysLT(1)R-dependent DC-mediated
      sensitization. CysLT(2)R-deficient BMDCs had increased CysLT(1)R-dependent LTD(4)
      induced ERK phosphorylation, whereas N-methyl LTC(4) activation of CysLT(2)R on
      WT BMDCs reduced such signaling. Activation of endogenously expressed CysLT(1)R
      and CysLT(2)R occurred over an equimolar range of LTD(4) and N-methyl LTC(4),
      respectively. Although the baseline expression of cell surface CysLT(1)R was not
      increased on CysLT(2)R-deficient BMDCs, it was upregulated at 24 h by a pulse of
      D. farinae, compared with WT or CysLT(2)R/LTC(4)S-deficient BMDCs. Importantly,
      treatment with N-methyl LTC(4) reduced D. farinae-induced CysLT(1)R expression on
      WT BMDCs. Thus, CysLT(2)R negatively regulates the development of cys-LT
      dependent Th2 pulmonary inflammation by inhibiting both CysLT(1)R signaling and
      D. farinae-induced LTC(4)S-dependent cell surface expression of CysLT(1)R on DCs.
      Furthermore, these studies highlight how the biologic activity of cys-LTs can be
      tightly regulated by competition between these endogenously expressed receptors.

PMID- 23002439
TI  - Genetic depletion of complement receptors CD21/35 prevents terminal prion disease
      in a mouse model of chronic wasting disease.
AB  - The complement system has been shown to facilitate peripheral prion pathogenesis.
      Mice lacking complement receptors CD21/35 partially resist terminal prion disease
      when infected i.p. with mouse-adapted scrapie prions. Chronic wasting disease
      (CWD) is an emerging prion disease of captive and free-ranging cervid populations
      that, similar to scrapie, has been shown to involve the immune system, which
      probably contributes to their relatively facile horizontal and environmental
      transmission. In this study, we show that mice overexpressing the cervid prion
      protein and susceptible to CWD (Tg(cerPrP)5037 mice) but lack CD21/35 expression
      completely resist clinical CWD upon peripheral infection. CD21/35-deficient
      Tg5037 mice exhibit greatly impaired splenic prion accumulation and replication
      throughout disease, similar to CD21/35-deficient murine prion protein mice
      infected with mouse scrapie. TgA5037;CD21/35(-/-) mice exhibited little or no
      neuropathology and deposition of misfolded, protease-resistant prion protein
      associated with CWD. CD21/35 translocate to lipid rafts and mediates a strong
      germinal center response to prion infection that we propose provides the optimal
      environment for prion accumulation and replication. We further propose a
      potential role for CD21/35 in selecting prion quasi-species present in prion
      strains that may exhibit differential zoonotic potential compared with the
      parental strains.

PMID- 23002441
TI  - A20 and CYLD do not share significant overlapping functions during B cell
      development and activation.
AB  - The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are
      central negative regulators of NF-kappaB signaling. Both can act by removing
      nonproteolytic K63-linked polyubiquitin chains from an overlapping set of
      signaling molecules. In B cells, A20 deficiency results in hyperactivity, loss of
      immune homeostasis, inflammation, and autoimmunity. The reported consequences of
      CYLD deficiency are controversial, ranging from an absence of effects to dramatic
      B cell hyperplasia. These differences could be due to varying compensation for
      the loss of CYLD function by A20. Therefore, to explore potential overlapping
      physiological functions between A20 and CYLD, we generated and characterized
      A20/CYLD double-deficient B cells. Interestingly, the lack of both A20 and CYLD
      did not exacerbate the developmental defects and hyperresponsive activity of A20
      deficient B cells. In addition, the extent of B cell activation after in vitro
      stimulation with anti-CD40, LPS, and CpG was comparable in B cells lacking
      A20/CYLD and A20 alone. However, in response to BCR cross-linking, we observed
      small but reproducible additive effects of the lack of A20 and CYLD. Taken
      together, our results demonstrate that A20 and CYLD do not share significant
      functions during B cell development and activation.

PMID- 23002440
TI  - CD40/CD154 blockade inhibits dendritic cell expression of inflammatory cytokines
      but not costimulatory molecules.
AB  - Blockade of the CD40/CD154 pathway remains one of the most effective means of
      promoting graft survival following transplantation. However, the effects of
      CD40/CD154 antagonism on dendritic cell (DC) phenotype and functionality
      following transplantation remain incompletely understood. To dissect the effects
      of CD154/CD40 blockade on DC activation in vivo, we generated hematopoietic
      chimeras in mice that expressed a surrogate minor Ag (OVA). Adoptive transfer of
      OVA-specific CD4(+) and CD8(+) T cells led to chimerism rejection, which was
      inhibited by treatment with CD154 blockade. Surprisingly, CD154 antagonism did
      not alter the expression of MHC and costimulatory molecules on CD11c(+) DCs
      compared with untreated controls. However, DCs isolated from anti-CD154-treated
      animals exhibited a significant reduction in inflammatory cytokine secretion.
      Combined blockade of inflammatory cytokines IL-6 and IL-12p40 attenuated the
      expansion of Ag-specific CD4(+) and CD8(+) T cells and transiently inhibited the
      rejection of OVA-expressing cells. These results suggest that a major effect of
      CD154 antagonism in vivo is an impairment in the provision of signal three during
      donor-reactive T cell programming, as opposed to an impact on the provision of
      signal two. We conclude that therapies designed to target inflammatory cytokines
      during donor-reactive T cell activation may be beneficial in attenuating these
      responses and prolonging graft survival.

PMID- 23002442
TI  - A serpinB1 regulatory mechanism is essential for restricting neutrophil
      extracellular trap generation.
AB  - NETosis (neutrophil extracellular trap [NET] generation), a programmed death
      pathway initiated in mature neutrophils by pathogens and inflammatory mediators,
      can be a protective process that sequesters microbes and prevents spread of
      infection, but it can also be a pathological process that causes inflammation and
      serious tissue injury. Little is known about the regulatory mechanism.
      Previously, we demonstrated that serpinb1-deficient mice are highly susceptible
      to pulmonary bacterial and viral infections due to inflammation and tissue injury
      associated with increased neutrophilic death. In this study, we used in vitro and
      in vivo approaches to investigate whether SerpinB1 regulates NETosis. We found
      that serpinb1-deficient bone marrow and lung neutrophils are hypersusceptible to
      NETosis induced by multiple mediators in both an NADPH-dependent and -independent
      manner, indicating a deeply rooted regulatory role in NETosis. This role is
      further supported by increased nuclear expansion (representing chromatin
      decondensation) of PMA-treated serpinb1-deficient neutrophils compared with wild
      type, by migration of SerpinB1 from the cytoplasm to the nucleus of human
      neutrophils that is coincident with or preceding early conversion of lobulated
      (segmented) nuclei to delobulated (spherical) morphology, as well as by the
      finding that exogenous human recombinant SerpinB1 abrogates NET production.
      NETosis of serpinb1-deficient neutrophils is also increased in vivo during
      Pseudomonas aeruginosa lung infection. The findings identify a previously
      unrecognized regulatory mechanism involving SerpinB1 that restricts the
      production of NETs.

PMID- 23002444
TI  - Terra incognito: the ureter in urinary tract infection.

PMID- 23002443
TI  - Adipocyte-derived soluble factor(s) inhibits early stages of B lymphopoiesis.
AB  - B lymphopoiesis declines with age, and in rabbits this occurs by 8 wk of age. We
      found that CFU fibroblasts (CFU-Fs) in the bone marrow (BM) decrease 10-fold by a
      few weeks of age and that the CFU-Fs preferentially differentiate into adipocytes
      instead of osteoblasts. BM becomes filled with fat spaces during this time,
      making rabbit a unique model to study the effects of accelerated fat accumulation
      on B lymphopoiesis. We show that adipocytes of both rabbit and human secrete a
      soluble factor(s) that inhibits B lymphopoiesis, and we tested if this inhibition
      was due to effects on the BM stroma or hematopoietic progenitors. Pretreatment of
      BM mononuclear cells with adipocyte conditioned medium dramatically inhibited
      their differentiation into proB cells in cocultures with OP9 stromal cells. In
      contrast, pretreatment of OP9 stromal cells with adipocyte conditioned medium had
      no effect on B lymphopoiesis. Using human hematopoietic stem cells, we show that
      inhibition by the adipocyte-derived factor occurred at the common lymphoid
      progenitor to preproB cell stage. We propose that the age-related decline in B
      lymphopoiesis is due to a decrease in CFU-Fs, an increase in adipocytes, and an
      adipocyte-derived factor that blocks B lymphopoiesis at the common lymphoid
      progenitor to preproB cell stage.

PMID- 23002445
TI  - Elevated interleukin 8 and T-helper 1 and T-helper 17 cytokine levels prior to
      antiretroviral therapy in participants who developed immune reconstitution
      inflammatory syndrome during ACTG A5164.
AB  - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) reflects an
      aberrant immune response that can develop in human immunodeficiency virus
      infected patients initiating antiretroviral therapy (ART). Its pathogenesis
      remains unclear. METHODS: We performed a nested case-control study using
      specimens from ACTG A5164. We compared plasma biomarkers and T-cell subsets in 19
      IRIS and 39 control participants at study entry, ART initiation, and IRIS and
      used conditional logistic regression to develop IRIS predictive models. We
      evaluated the effect of corticosteroids on biomarker levels. RESULTS: Eleven and
      8 participants developed paradoxical and unmasking IRIS, respectively, none while
      still receiving corticosteroids. Compared to controls, cases displayed elevations
      at study entry in interleukin (IL) 8, T-helper (Th) 1 (IL-2, interferon [IFN]
      gamma, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that
      persisted through ART initiation and IRIS. In logistic regression, baseline
      higher IFN-gamma and TNF were strong predictors of IRIS. Participants who
      received corticosteroids and later developed IRIS had marked increases in IL-6,
      IL-8, and IFN-gamma at the time of IRIS. T-cell activation markers did not differ
      in cases and controls prior to ART but were increased in cases at the time of
      IRIS. CONCLUSIONS: Increased IL-8, Th1, and Th17 cytokine levels in IRIS patients
      precede ART initiation and could help identify patient populations at higher risk
      for IRIS.

PMID- 23002446
TI  - Capsular switching in group B Streptococcus CC17 hypervirulent clone: a future
      challenge for polysaccharide vaccine development.
AB  - BACKGROUND: The capsular polysaccharide (CPS) is an important virulence factor
      and a vaccine target of the major neonatal pathogen group B Streptococcus (GBS).
      Population studies revealed no strong correlation between CPS type and multilocus
      sequence typing (MLST) cluster, with the remarkable exception of the worldwide
      spread of hypervirulent GBS CC17, which were all until recently CPS type III.
      METHODS: A total of 965 GBS strains from invasive infection isolated in France
      were CPS typed and the presence of the CC17-specific surface protein encoding
      gene hvgA gene was investigated. Three hvgA-positive GBS strains screened were
      surprisingly CPS type IV and thus further characterized by MLST typing, pulsed
      field gel electrophoresis (PFGE), and whole genome sequencing. RESULTS: MLST and
      PFGE demonstrated a capsular switching from CPS type III to IV within the highly
      homogeneous GBS CC17. Sequence analysis revealed that this capsular switch was
      due to the exchange of a 35.5-kb DNA fragment containing the entire cps operon.
      CONCLUSIONS: This work shows that GBS CC17 hypervirulent strains have switched
      one of their main vaccine targets. Thus, continued surveillance of GBS population
      remains of the utmost importance during clinical trials of conjugate GBS
      vaccines.

PMID- 23002447
TI  - Escherichia coli-mediated impairment of ureteric contractility is uropathogenic
      E. coli specific.
AB  - BACKGROUND: Ureters are fundamental for keeping kidneys free from uropathogenic
      Escherichia coli (UPEC), but we have shown that 2 strains (J96 and 536) can
      subvert this role and reduce ureteric contractility. To determine whether this is
      (1) a widespread feature of UPEC, (2) exhibited only by UPEC, and (3) dependent
      upon type 1 fimbriae, we analyzed strains representing epidemiologically
      important multilocus sequence types ST131, ST73, and ST95 and non-UPEC E. coli.
      METHODS: Contractility and calcium transients in intact rat ureters were compared
      between strains. Mannose and fim mutants were used to investigate the role of
      type 1 fimbriae. RESULTS: Non-UPEC had no significant effect on contractility,
      with a mean decrease after 8 hours of 8.8%, compared with 8.8% in controls. UPEC
      effects on contractility were strain specific, with decreases from 9.47% to
      96.7%. Mannose inhibited the effects of the most potent strains (CFT073 and
      UTI89) but had variable effects among other UPEC strains. Mutation and
      complementation studies showed that the effects of the UTI89 cystitis isolate
      were fimH dependent. CONCLUSIONS: We find that (1) non-UPEC do not affect
      ureteric contractility, (2) impairment of contractility is a common feature of
      UPEC, and (3) the mechanism varies between strains, but for the most potent UPEC
      type 1 fimbriae are involved.

PMID- 23002449
TI  - A case of huge malignant peripheral nerve sheath tumor (MPNST) in the back.

PMID- 23002448
TI  - Increase in rates of hospitalization due to laboratory-confirmed influenza among
      children and adults during the 2009-10 influenza pandemic.
AB  - BACKGROUND: The Emerging Infections Programs (EIP) network has conducted
      population-based surveillance for hospitalizations due to laboratory-confirmed
      influenza among children since 2003, with the network expanding in 2005 to
      include adults. METHODS: From 15 April 2009 through 30 April 2010, the EIP
      conducted surveillance among 22.1 million people residing in 10 states. Incidence
      rates per 100 000 population were calculated using US Census Bureau data. Mean
      historic rates were calculated on the basis of previously published and
      unpublished EIP data. RESULTS: During the 2009 pandemic of influenza A virus
      subtype H1N1 infection, rates of hospitalizations due to laboratory-confirmed
      influenza were 202, 88, 49, 31, 27, 36, 28, and 27 episodes per 100 000 among
      persons aged <6 months, 6-23 months, 2-4 years, 5-17 years, 18-49 years, 50-64
      years, 65-74 years, and >=75 years, respectively. Comparative mean rates from
      previous influenza seasons during which EIP conducted surveillance were 153, 53,
      20, 6, 4, 8, 20, and 56 episodes per 100 000 among persons aged <6 months, 6-23
      months, 2-4 years, 5-17 years, 18-49 years, 50-64 years, 65-74 years, and >=75
      years, respectively. CONCLUSIONS: During the pandemic, rates of hospitalization
      due to laboratory-confirmed influenza among individuals aged 5-17 years and 18-49
      years increased 5-fold and 6-fold, respectively, compared with mean rates from
      previous influenza seasons. Hospitalization rates for other pediatric and adult
      age groups increased, compared with mean rates from previous influenza seasons,
      whereas the rate among individuals aged >=75 years decreased.

PMID- 23002450
TI  - Cancer mortality attributable to tobacco in Asia based on the WHO Global Report.

PMID- 23002451
TI  - Through the gaps.

PMID- 23002452
TI  - Extreme weather.

PMID- 23002453
TI  - Return to sender.

PMID- 23002454
TI  - [Abstracts of the 27th Congress of Physical Medicine and Rehabilitation. October
      8-10, 2012. Toulouse, France].

PMID- 23002455
TI  - Reflections: neurology and the humanities: the Wimshurst machine.

PMID- 23002457
TI  - Abstracts of the 82nd Annual Meeting of the American Thyroid Association.
      September 19-23, 2012. Quebec City, Quebec, Canada.

PMID- 23002456
TI  - Postdocs: A voice for the voiceless.

PMID- 23002459
TI  - Abstracts of the 26th Annual North American Cystic Fibrosis Conference. October
      11-13, 2012. Orlando, Florida, USA.

PMID- 23002458
TI  - Upper urinary tract urothelial cancers: where it is A:T.
AB  - Despite a ban on the use of plants of the Aristolochia genus in herbal medicine,
      as they contain known carcinogens, urothelial carcinoma attributable to the use
      of this plant seems to be more common than previously thought.

PMID- 23002460
TI  - [Developmental anatomy of anomalous structure and investigation of medicinal
      parts Sophora flavescens].
AB  - OBJECTIVE: To elucidate the composition structure of "annual rings" and the
      formation process of anomalous structures in Sophora flavescens, and further
      discuss the medicinal parts of S. flavescens. METHOD: Based on investigation on
      S. flavescens in its producing areas, the morphology of root systems was
      observed, and the developmental anatomy of roots was researched. RESULT: Creeping
      underground rhizomes of S. flavescen existed in some parts of the north place,
      there were many differences in appearance characters and microscopic features
      between these roots and rhizomes. Parenchyma cells in secondary xylem regained
      meristematic ability, became into anomalous cambia, and then developed into
      anomalous structures. "Annual rings" in transverse section of S. flavescens were
      not actually growth rings, they were made up of anomalous parenchyma girdle in
      secondary xylem and normal secondary structure. CONCLUSION: Roots are the
      medicinal parts of S. flavescens. This paper suggests that "annual rings" in the
      decoction pieces of S. flavescens should be called "annular structure".

PMID- 23002461
TI  - [Influences of physical, psychological and social adjustment status on the sleep
      quality of people between 18 na 55 years old in Suzhu city].

PMID- 23002462
TI  - [Analysis on the characteristics of alimentary canal cancer deaths in Guangdong
      province].

PMID- 23002463
TI  - [Analysis monitoring on data and quality evaluation of Japanese encephalitis
      laboratory network in Guizhou].

PMID- 23002464
TI  - [Epidemiological study on data involving 61 hospitalized cases with Huaiyangshan
      hemorrhagic fever in Wuhan].

PMID- 23002465
TI  - [Analysis of misdiagnosis for 1 cases suspected diphtheria].

PMID- 23002466
TI  - [Epidemiological investigation on college student' periostitis caused by fatigue
      in Anhui province].

PMID- 23002467
TI  - Diplopia after strabismus surgery.
AB  - The presence of diplopia is an undesirable result following strabismus surgery.
      There are a variety of scenarios where diplopia exists prior to strabismus
      surgery, and, after surgery, has either been alleviated or decreased to a
      magnitude amenable to prism correction. In other cases, the patient does not
      experience diplopia prior to the strabismus surgery, but there exists a definite
      risk of diplopia after the surgery. In the current review, I examine the
      literature to help determine the incidence of diplopia after strabismus surgery.

PMID- 23002468
TI  - Diplopia after glaucoma surgery.
AB  - The occurrence of strabismus and symptomatic diplopia following glaucoma surgery
      is becoming more common as the use of implanted setons increases. Understanding
      the factors contributing to the diplopia is critical to the development of
      treatment strategies to alleviate the patient's symptoms.

PMID- 23002469
TI  - Nonsurgical management of diplopia.
AB  - Diplopia is a potential undesirable outcome of nearly any ocular surgery. In some
      cases, the unexpected strabismus and diplopia resolve quickly without
      intervention, especially if due to swelling or minor insult from the surgical
      procedure. When double vision persists, effective treatment may be more elusive
      in patients in which the strabismus is the result of a restrictive process. The
      sudden onset of strabismus makes treatment more challenging. Frequently these
      patients will require surgical intervention. Where possible, patients may be
      managed with nonsurgical treatments until the time of surgery or indefinitely if
      successful and acceptable to the patient. Diplopia has been documented as a
      result of restrictive strabismus following vitreoretinal surgery, glaucoma
      surgery, orbital decompression surgery, strabismus surgery, orbital surgery,
      conjunctival surgery, cataract surgery, blepharoplasty, and others. The treatment
      of diplopia after ocular surgery is complicated by the incomitance and torsion
      that may be associated with restrictive strabismus as well as the variability of
      the deviation during healing. Nonsurgical treatment options include prisms or
      occlusion. Fresnel prisms are used primarily, but occasionally the prism is
      ground into the spectacles. Occlusion of the involved eye may be partial or
      complete, using a "pirate" patch, adhesive patch, Bangerter foil, tape, or
      related method.

PMID- 23002470
TI  - Diplopia following cosmetic surgery.
AB  - Cosmetic blepharoplasty is the most often performed procedure in plastic surgery
      and ophthalmic plastic surgery. Many complications have been reported including
      ectropion, exposure keratitis, hemorrhage, epiphora, infection, vision loss, and,
      very rarely, diplopia. Although uncommon, there have been several case reports
      and case series published evaluating possible causes of this problem, including
      aggressive excision of fat, wound-related inflammation, conjunctival edema, and
      temporary muscle disturbances. Although the inferior oblique muscle is most
      susceptible to injury, the inferior rectus and superior oblique muscles are also
      subject to trauma. When performing cosmetic blepharoplasties, surgeons should be
      cautious when dissecting fat pads and should do so under direct visualization.
      Meticulous cautery is also important to avoiding injury to the extraocular
      muscles. Fresnel prisms and Bangerter filters can be used to help alleviate
      diplopia in patients with small-angle strabismus. Surgical exploration and
      extraocular muscle surgery may be indicated in patients with diplopia that cannot
      be resolved with nonsurgical treatment.

PMID- 23002471
TI  - Diplopia secondary to orbital surgery.
AB  - Diplopia may occur following any type of ocular or pericocular surgery. The
      surgeries most frequently associated with postoperative diplopia include: repair
      of orbital fracture, endoscopic sinus surgery (from inadvertent orbital
      penetration), and orbital decompression for thyroid-related immune orbitopathy
      (TRIO). Postoperative diplopia after orbital tumor resection has been reported-
      e.g., after excision of fibrous dysplasia and osteoma. However, a recent case
      series suggests diplopia after orbital tumor resection is uncommon and transient.
      Surgical intervention for orbital trauma carries the highest risk of
      postoperative diplopia and will be the focus of this review. We will also present
      a case report of worsening diplopia following repair of orbital floor fracture to
      highlight potential motility issues that can arise when implants are employed to
      treat orbital floor fractures.

PMID- 23002472
TI  - Nonsurgical management of diplopia after orbital decompression surgery.
AB  - Orbital decompression is frequently performed in patients with thyroid eye
      disease. The indication for an orbital decompression in most patients is
      threatened visual loss from corneal exposure or optic neuropathy. One of the more
      common complications associated with orbital decompression is the development or
      worsening of diplopia. Often times, surgical intervention for strabismus is
      delayed after orbital decompression and in these cases, nonsurgical management of
      diplopia is invaluable to the patient. Nonsurgical management can include
      occlusion therapy, prism therapy, or even botulinum toxin injections into the
      extraocular muscles.

PMID- 23002473
TI  - Diplopia associated with refractive surgery.
AB  - When diplopia occurs after refractive surgery, a systematized approach to
      diagnosis and treatment is useful. First, determine if the problem is monocular
      or binocular. Monocular diplopia usually is caused by anterior segment
      complications and should be referred to an anterior segment surgeon. If the
      problem is binocular, determine if there is iatrogenic monovision. If monovision
      was created by the refractive surgery, determine if the double vision is due to
      fixation switch diplopia. If so, the monovision state needs to be reversed. If
      fixation switch is not the cause of the symptoms, try "optical rescue". If
      monovision is not present, check old refraction and motility records, and correct
      any residual refractive error. Strabismus may need to be treated with surgery,
      orthoptic exercises, or prisms.

PMID- 23002474
TI  - Nonsurgical management of diplopia after retinal surgery.
AB  - For those who manage strabismus in adults, the patient with diplopia following
      retinal surgery presents a challenge. Mechanical and sensory factors may combine
      to preclude single binocular vision, and neutralizing the patient's strabismus
      may not be sufficient to permit resolution of their diplopia. This paper reviews
      the issues involved and discusses some potential solutions.

PMID- 23002475
TI  - Surgical management of strabismus following vitreo-retinal surgery.
AB  - Motility disorders and strabismus after vitreo-retinal surgical intervention have
      multiple etiologic factors. The main focus here is strabismus following scleral
      buckling surgery. The preoperative evaluation of these patients must be inclusive
      for restrictions, redirected muscle forces, adherence syndromes, muscle weakness,
      and visual sensory disturbance. Restoration of binocular function is generally
      the goal of surgical intervention, but paramount to surgery is assessing the
      potential for binocular function. Surgical techniques for overcoming the barriers
      to fusion are discussed with clinical vignettes to illustrate the principal.
      Surgery, which is appropriately planned, based on theses principals can by highly
      successful in restoring visual functioning.

PMID- 23002476
TI  - ACAPN division news.

PMID- 23002477
TI  - [Impact of planning CT slice thickness on the accuracy of automatic target
      registration using the on-board cone-beam CT].
AB  - We have evaluated relationship between planning CT slice thickness and the
      accuracy of automatic target registration using cone-beam CT (CBCT). Planning CT
      images were acquired with reconstructed slice thickness of 1, 2, 3, 5, and 10mm
      for three different phantoms: Penta-Guide phantom, acrylic ball phantom, and
      pelvic phantom. After correctly placing the phantom at the isocenter using an in
      room laser, we purposely displaced it by moving the treatment couch and then
      obtained CBCT images. Registration between the planning CT and the CBCT was
      performed using automatic target registration software, and the registration
      errors were recorded for each planning CT data set with different slice
      thickness. The respective average and standard deviation of errors for 10 mm
      slice thickness CT in the lateral, longitudinal, and vertical directions (n=15
      data sets) were: 0.7 +/- 0.2mm, 0.8 +/- 0.2mm, and 0.2 +/- 0.2mm for the Penta
      Guide phantom; 0.5 +/- 0.4 mm, 0.6 +/- 0.3 mm, and 0.4 +/- 0.3 mm for the acrylic
      ball phantom; and 0.6 +/- 0.2 mm, 0.9 +/- 0.2 mm, and 0.2 +/- 0.2 mm for the
      pelvic phantom. We found that the mean registration errors were always less than
      1 mm regardless of the slice thickness tested. The results suggest that there is
      no obvious correlation between the planning CT slice thickness and the
      registration errors.

PMID- 23002478
TI  - [Usefulness of treatment evaluation of severe heart failure by ECG-gated
      myocardial SPECT].
AB  - Our purpose of study was to investigate the usefulness of treatment evaluation of
      severe heart failure by ECG-gated myocardial SPECT. We evaluated the cardiac
      function in the case of severe heart failure by gated SPECT and compared it with
      the cardiac function obtained by LVG, echocardiography, cardiac MRI, and BNP
      values. We investigated the correlation of EF, time lag of wall motion between
      the septal and lateral walls of the left ventricle for CRT and wall thickening
      (WT). We classified the LV into basal, middle and apical areas for comparison of
      WT. We investigated the effect of a perfusion defect score in these comparisons.
      The gated SPECT results were correlated with comparative subjects in EF. The
      results were correlated with MRI on the middle area of the LV in the comparison
      of WT. We thought it was possible that there was an effect from a perfusion
      defect score in a time lag comparison of wall motion. Treatment evaluation of
      severe heart failure by gated SPECT is useful, because it is able to obtain three
      dimensional cardiac function analysis, and it offers objectivity and reproducible
      quantitative evaluation. At the same time, perfusion SPECT is helpful for CRT and
      LV-plasty.

PMID- 23002479
TI  - [Evaluating photonuclear activation for clearance of decommissioned medical
      linear accelerators].
AB  - In a linear accelerator (linac) that operates at greater than an accelerating
      energy of 10 MV, neutrons are generated by a photonuclear reaction and the head
      section of the linac becomes radioactive. The purpose of this research is to
      obtain data for ensuring the safety of linac decommissioning and upgrading. The
      decommissioned linac investigated in this study was a Clinac 2100 C/D (Varian)
      installed in April 1999. Its total time of use was 2757.7 h (equivalent to
      496,386 Gy). The dosage for its last three months of use was 7213.67 Gy. After
      being allowed to sit for a 7-day cooling period, the apparatus was disassembled
      and the parts of the gantry head portion were removed. The ambient dose
      equivalent rates, H*(10), (microSv/h) from the removed parts were measured in
      air, at a location with low background, by using a gamma ray scintillation survey
      meter. The target was also analyzed with an HP-Ge semiconductor detector, in
      order to identify the nuclides responsible for the observed radiation. On day 7
      after the last use of the linac, the ambient dose equivalent rates, H*(10),
      (microSv/h) in air at the surface of all parts, except the target and the
      beryllium window, were within the limit of normal background radiation. The
      measured value (microSv/h) for the beryllium window decreased to within the
      background limit on day 10. The measured value (microSv/h) of the target
      decreased to about 1.5 times the background on day 19. At a distance of 10 cm,
      all the parts were within the background limit after the initial 7-day cooling
      period. In the analysis of the target with the HP-Ge semiconductor detector,
      peaks at 125, 333, 352, 356, 426, 511, 583, 609, 689, 811, 835, 911, 969, 1091,
      1099, 1120, 1173, 1238, 1292, 1333, 1461 and 1764keV were detected on day 23.
      Seven months after the linac was last used, peaks were detected at 352, 511, 583,
      609, 835, 911, 969, 1120, 1173, 1238, 1333, 1461 and 1764 keV. From these
      results, the natural radioactive nuclides can be assigned as 40K, 208Tl, 214Pb,
      214Bi and 228Ac; the short half-life nuclides can be assigned as 59Fe, 58Co, 185W
      and 196Au; and the long half-life nuclides can be assigned as 54Mn and 60Co.
      These results show that photonuclear activation of parts is important in regard
      to clearance. Currently, there are no regulations that specify criteria for
      evaluating radioactivation. Such criteria are needed to establish suitable
      protocols for the clearance of radioactivated materials.

PMID- 23002480
TI  - [Development of the image registration program for portal and DRR images in
      radiation therapy].
AB  - In this article, the authors propose an image registration program of portal
      images and digitally reconstructed radiography (DRR) images used as simulation
      images for external beam radiation therapy planning. First, the center of the
      radiation field in a portal image taken using a computed radiograhy cassette is
      matched to the center of the portal image. Then scale points projected on a DRR
      image and the portal image are deleted, and the portal image with the radiation
      field is extracted. Registration of the DRR and portal images is performed using
      mutual information as the registration criterion. It was found that the absolute
      displacement misregistrations in two directions (x, y) were 1.2 +/- 0.7mm and 0.5
      +/- 0.3 mm, respectively, and rotation disagreement about the z axis 0.3 +/- 0.3
      degrees. It was concluded the proposed method was applicable to image
      registration of portal and DRR images in radiation therapy.

PMID- 23002481
TI  - [Polymer gel dosimetry--the dose response for X-ray irradiation].
AB  - Polymer gel dosimetry has been considered a promising technique for clinical use,
      but this potential has not yet been fully realized in Japan. One reason may be
      because the commercialized gel detector, BANG gel, is expensive and it is only
      produced abroad. A second reason is the difficulty of controlling dose
      sensitivity of the gel so that it is stable under ordinary clinical conditions.
      In this work we introduce two types of gel detectors (MAG and PAG) which we
      produced in-house. First the method of fabrication of gel is presented in detail,
      then the dose responses of MAG and PAG for X-ray irradiation are evaluating for
      MRI and X-ray CT scanning. The MAG-type gel is useful in low contrast dosimetry
      because of the high sensitivity in its dose response (R2). The PAG-type gel is
      effective for dosimetry in multiple field irradiations because its dose response
      (CT value) has reproducibility independent of the different irradiation
      conditions. Finally, we summarize the potential for clinical use of polymer gel
      dosimetry with these gel detectors.

PMID- 23002482
TI  - [Correlation between required quality assurance equipment and radiation therapy
      institutional level].
AB  - Radiotherapy institutions carry out various types of treatments such as
      conventional radiation treatment, stereotactic radiotherapy (SRT), intensity
      modulated radiation therapy (IMRT) and image-guided radiotherapy (IGRT).
      According to the radiation treatment type, various kinds of quality assurance
      (QA) equipment are used to maintain the accurate dose delivery to a patient with
      accurate positioning. The aim of this report was to propose the QA equipment
      required at various institutional levels. The institution levels were categorized
      according to the radiation treatment cases. Institutions in the basic category
      used conventional radiotherapy techniques employing field sizes larger than 4 cm
      x 4 cm, or they had no full-time radiation oncologist. In addition to the basic
      level, five other categories were defined which were based on being able to carry
      out total body irradiation, three-dimensional conformal radiation therapy/SRT,
      IMRT, and IGRT. Minimum QA equipment requirements were proposed for each level.
      This proposal will facilitate the purchase of QA equipment for the installation
      or refurbishing of a linear accelerator.

PMID- 23002484
TI  - Sim for students: master the use of simulation in your classroom.

PMID- 23002483
TI  - Is EMS a game? Inefficiency can cost patient lives.

PMID- 23002485
TI  - Do no harm: it's important to not inflict unnecessary pain.

PMID- 23002486
TI  - Difficult airway: providers treat patient with multiple gunshot wounds.

PMID- 23002487
TI  - Richmond Ambulance Authority creates comprehensive culture of safety model.

PMID- 23002488
TI  - Stroke of the clock: 'time is brain' when treating stroke patients.

PMID- 23002489
TI  - EPI coasters: hang on to the bar.

PMID- 23002490
TI  - Improving team performance during the preprocedure time-out in pediatric
      interventional radiology.
AB  - BACKGROUND: The preprocedure time-out is a high-profile safety measure, and
      compliance is coming under increasing scrutiny. A checklist-based scoring system
      was developed to rigorously assess compliance, and a system of video monitoring
      and feedback was used to track performance and improve the time-out process in
      pediatric interventional radiology. METHODS: A time-out "script" containing a
      series of observable behaviors to be performed collectively by the physician,
      nurse, and technologist before each interventional procedure was used to create a
      checklist. A procedure room equipped with an audio/video recording system allowed
      capture of time-outs for later review. The reviewer scored one or two time-outs
      each week, and the results were posted to provide feedback. RESULTS: The process
      of continual feedback and modification led to substantial improvements in time
      out performance during a three-year period. Analysis of subscores revealed common
      failure modes that were subsequently addressed. The scoring checklist was also
      modified after analysis suggested redundant or unnecessary items. Gains were
      noted in the efficiency of the time-out protocol, which took more than 1 minute
      in the initial stages but soon shortened to 30-45 seconds as the team gained
      experience. Assessment of scoring consistency across three independent observers
      revealed 93% interobserver agreement and 95% intraobserver agreement.
      Clarification of the scoring criteria led to improved consistency (97% and 98%
      inter- and intraobserver agreement, respectively). CONCLUSIONS: The combination
      of a time-out checklist, recorded procedures, review, and feedback produced not
      only improvements in time-out performance but also improvements in the scoring
      system and time-out process.

PMID- 23002491
TI  - Volume-related differences in emergency department performance.
AB  - BACKGROUND: Emergency departments (EDs) are an important source of care for a
      large segment of the population of the United States. In 2009 there were more
      than 136 million visits to the ED each year, and more than half of hospital
      admissions begin in the ED. Measurement and monitoring of emergency department
      performance has been prompted by The Joint Commission's patient flow standards. A
      study was conducted to attempt to correlate ED volume and other operating
      characteristics with performance on metrics. METHODS: A retrospective analysis of
      the Emergency Department Benchmarking Alliance annual ED survey data for the most
      recent year for which data were available (2009) was performed to explore
      observed patterns in ED performance relative to size and operating
      characteristics. The survey was based on 14.6 million ED visits in 358 hospitals
      across the United States, with an ED size representation (sampling) approximating
      that of the Emergency Medicine Network (EM Net). RESULTS: Larger EDs (with higher
      annual volumes) had longer lengths of stay (p < .0001), higher left without being
      seen rates (p < .0001), and longer door-to-physician times (p < .0001), all
      suggesting poorer operational performance. Operating characteristics indicative
      of higher acuity were associated with worsened performance on metrics and lower
      acuity characteristics with improved performance. CONCLUSION: ED volume, which
      also correlates with many operating characteristics, is the strongest predictor
      of operational performance on metrics and can be used to categorize EDs for
      comparative analysis. Operating characteristics indicative of acuity also
      influence performance. The findings suggest that ED performance measures should
      take ED volume, acuity, and other characteristics into account and that these
      features have important implications for ED design, operations, and policy
      decisions.

PMID- 23002492
TI  - Discontinuation of antihyperglycemic therapy after acute myocardial infarction:
      medical necessity or medical error?
AB  - BACKGROUND: A national Medicare database indicated that one in eight older
      patients with diabetes was discharged off all antihyperglycemic therapy (AHT)
      following acute myocardial infarction (AMI). This practice was associated with
      increased one-year mortality, but the reasons for stopping AHT were not known. A
      study was conducted to determine whether such practice might be due to medical
      necessity (that is, a new contraindication) or oversight--in which case a quality
      improvement opportunity might exist. METHODS: Some 327 diabetic patients were
      identified who were hospitalized with AMI during a one-year period at an academic
      medical center and an affiliated community hospital. Detailed chart reviews were
      conducted on the 217 patients with AMI as a principal diagnosis who were admitted
      on AHT (insulin, 81). Twenty-five patients (11.5%) were discharged off AHT, 24
      (96%) of whom received some AHT in the hospital, mostly as insulin sliding scale.
      One patient's (4%) AHT was stopped because of a change in care goals, a second
      developed recurrent hypoglycemia, and a third had entirely normal in-hospital
      blood glucose after AHT discontinuation. The remaining 22 patients (88%) were
      categorized as being discharged off AHT without justification. The
      demographic/clinical characteristics of those discharged on versus off AHT were
      similar, except for better left ventricular ejection fraction (LVEF) in the
      latter. CONCLUSIONS: The percentage of diabetic patients discharged off AHT
      following AMI was nearly identical to that in a national database (approximately
      one out of eight). No clear reason for this practice could be found in nearly 90%
      of the cases, suggesting that it may often constitute a medical error for a
      growing population of diabetic patients with ischemic heart disease.

PMID- 23002494
TI  - Using an Objective Structured Clinical Examination to test adherence to Joint
      Commission National Patient Safety Goal--associated behaviors.
AB  - BACKGROUND: A study was conducted at a tertiary care academic medical center to
      assess a simulation-based, single-station Objective Structured Clinical
      Examination (OSCE) designed to evaluate intern trainees' familiarity with and
      adherence to behaviors associated with Joint Commission National Patient Safety
      Goals and The Joint Commission Universal Protocol for Preventing Wrong Site,
      Wrong Procedure, Wrong Person Surgery. METHOD: Subjects were interns, from all
      disciplines, completing basic skills training during intern orientation. The OSCE
      scenario was designed to assess 13 behaviors associated with four National
      Patient Safety Goals (1, 2, 3, and 7) from 2009 and 2010 and the Universal
      Protocol. Sessions were digitally recorded and independently reviewed by two
      observers, who scored behaviors using a standardized score sheet. Behaviors were
      assigned point values and tabulated for all trainees. Kappa coefficient was
      calculated to assess interrater reliability. RESULTS: One-hundred eleven (74.5%)
      of 149 interns completed the station. The average time to completion was 6.9
      minutes (standard deviation [SD] 1.8; range, 3.5-12.6). Interns scored an average
      of 9.5 points (SD, 4.7; range, 2-20; mode, 8) of 26. The interrater reliability
      for the two reviewers was 0.9. Interns most frequently requested chlorhexidine to
      sterilize the patient's skin (98.2% of interns demonstrated); identifying an
      unlabeled medication vial as inappropriate for use was the most frequently missed
      item (8.1% of interns demonstrated). CONCLUSIONS: Behaviors related to tenets of
      patient safety and quality care can be assessed using a simple to design and
      execute OSCE. Using simulation to test behaviors associated with the National
      Patient Safety Goals may be a desirable adjunct to traditional simple knowledge
      based tests.

PMID- 23002495
TI  - Improving presurgical pupil dilation for cataract surgery patients.
AB  - Insufficient pupil dilation, a common challenge in cataract surgery, may lead to
      surgical complications. After a quality improvement project was conducted, the
      proportion of patients with the desired pupil dilation of > or = 7 mm increased
      from 39.5% to 88.0% (Implementation phase) and then to 82.2% (Sustaining phase).

PMID- 23002493
TI  - Is it possible to identify risks for injurious falls in hospitalized patients?
AB  - BACKGROUND: Patient falls are among the most commonly reported adverse hospital
      events with more than one million occurring annually in the United States;
      approximately 10% result in serious injury. A retrospective study was conducted
      to determine predictors and outcomes of fall injuries among a cohort of adult
      hospitalized patients. METHODS: Data were obtained regarding patients who
      sustained an initial fall in hospital during a 26-month period from 16 adult
      general medical and surgical units in an urban university-affiliated community
      hospital. Data on intrinsic (individual) factors, extrinsic (environmental)
      factors, and situational activities were collected via nurse and patient
      interviews, patient examinations, and audits of incident reports and electronic
      health records. Fall injuries were classified as none/any for analyses.
      Unadjusted odds ratios [ORs] and 95% confidence intervals [CIs] for each of the
      variables of interest with fall injury were generated using logistic regressions.
      RESULTS: The 784 patients had a median age of 63.5 years (range, 20 to > 90
      years), 390 (50%) were women, and 526 (67%) were black. Some 228 (29%) fallers
      sustained injury; patients who were white (OR: 2.23; 95% CI: 1.62, 3.08), or were
      administered a selective serotonin reuptake inhibitor (OR: 1.04; 95% CI: 1.04,
      2.67), two antipsychotic agents (OR: 3.26; 95% CI: 1.20, 8.90), an opiate (OR:
      1.59; 95%; CI: 1.14, 2.20), or a diuretic non-antihypertensive agent (OR: 1.53;
      95% CI: 1.03, 2.26) were more likely to sustain an injury. Home-based wheelchair
      use was protective of fall injury (OR: 0.20; 95% CI: 0.05, 0.84). Seventy-nine
      percent of the patients had been designated as "high" fall risk within 24 hours
      before the fall. CONCLUSIONS: Few variables were able to distinguish patients who
      sustained injury after a hospital fall, further challenging clinicians' efforts
      to minimize hospital-related fall injury.

PMID- 23002496
TI  - Will continuous surveillance monitoring of vital signs provide cheaper, safer,
      and better hospital care for all?

PMID- 23002498
TI  - Patient's page. Oral cancer.

PMID- 23002499
TI  - Digital records at the College of Dentistry: a student's perspective.

PMID- 23002497
TI  - Developing a continuous monitoring infrastructure for detection of inpatient
      deterioration.
AB  - A physiologic database infrastructure, composed of a patient monitoring system
      and a data processing and storage system, enables the detection of deterioration
      in noncritical patients, thereby helping to prevent failure-to-rescue events.

PMID- 23002500
TI  - Faculty spotlight OU College of Dentistry Dr. Sharukh Khajotia.

PMID- 23002501
TI  - If you have patients who are public employees...

PMID- 23002502
TI  - Social media scoop--summer 2012.

PMID- 23002503
TI  - Oral cancer update 2012. Be ever vigilant in diagnosis and early detection.

PMID- 23002504
TI  - Comparing indirect fluorescent antibody assays to rapid diagnostic tests for the
      detection of influenza A(H1N1)pdm09.

PMID- 23002505
TI  - Is atypical pneumonia becoming...more typical? Molecular testing may help to
      answer that question, and enhance diagnosis and management of a challenging set
      of diseases.

PMID- 23002506
TI  - Breast cancer prognostic markers: where are we now?

PMID- 23002507
TI  - Gene expression profiling: a validated molecular complement to standard
      clinicopathologic evaluation in difficult-to-diagnose metastatic tumors.

PMID- 23002508
TI  - Blood gas: a brief anecdotal history by one who has been there.

PMID- 23002509
TI  - CLIA inspection deficiencies--what they mean and how to avoid them.

PMID- 23002510
TI  - Voice recognition technology vs. manual transcription: Is voice recognition
      technology superior to manual transcription for surgical pathology--in terms of
      return on investment? A formal study says the answer is no.

PMID- 23002511
TI  - IVD testing for CF patients: testing patients with cystic fibrosis for
      respiratory infections is crucial during flu season, and the use of agar-based
      systems is recommended.

PMID- 23002512
TI  - Shining a light on vitamin D testing.

PMID- 23002513
TI  - Prescription drug misuse: are we really making progress against this health
      epidemic?

PMID- 23002514
TI  - OSHA's stance on safety incentive programs.

PMID- 23002515
TI  - Welding fume exposures and controls.

PMID- 23002516
TI  - Stepping up the pace.

PMID- 23002517
TI  - New advances in global SDS management.

PMID- 23002518
TI  - Major changes in the OSHA HazCom Standard.

PMID- 23002519
TI  - Beyond ANSI: obtaining the best possible eye protection.

PMID- 23002520
TI  - Designing for workplace electrical safety.

PMID- 23002521
TI  - New standards change the landscape of walkway safety.

PMID- 23002522
TI  - Are you putting your employees at risk?

PMID- 23002523
TI  - Zero incident goals motivate risk-taking, not excellence.

PMID- 23002524
TI  - Classical leadership.

PMID- 23002526
TI  - The future of the insurance broker/advisor.

PMID- 23002525
TI  - Ways to trim college costs.

PMID- 23002527
TI  - Seven tips for landing an SBA loan.

PMID- 23002528
TI  - Dr. Norman Becker--a personal tribute.

PMID- 23002529
TI  - The art of case presentation.

PMID- 23002530
TI  - Increasing numbers of elderly are coming to your neighborhood.

PMID- 23002531
TI  - Ten under 10.

PMID- 23002532
TI  - American Heart Association updates CPR guidelines.

PMID- 23002533
TI  - To extract or not to extract, that is the question.

PMID- 23002534
TI  - A clinico-pathologic correlation. Oral melanocanthoma with concomitant epithelial
      mild-to-severe dysplasia.

PMID- 23002535
TI  - Oral ulceration with circumferential white rim: clinical significance.

PMID- 23002536
TI  - Sequence of events: caries to osteomyelitis.

PMID- 23002537
TI  - Continuing ED CRED.

PMID- 23002538
TI  - [Genotype I Japanese encephalitis virus is the main genotype in mosquito in
      Fujian province].
AB  - OBJECTIVE: To grasp the infection rate and genotypes of Japanese encephalitis
      virus (JEV) in mosquito in Fujian province. METHODS: Mosquito specimens in
      Sanming city, Jianyang city and Fuzhou city in Fujian province were collected in
      2010. RT-PCR was used to detect the JEV sequence from the mosquitoes by specific
      primers. The sequence splicing and the differentiation analysis for nucleotides,
      deduced amino acid sequence and phylogenetic tree were performed by the software
      of ATGC, Clustal X (1.83), MegAlign, GeneDoc 3.2 and Mega (4.0). RESULTS: Totally
      6987 mosquitoes were collected and main species was Culex tritaeniorhynchus and
      Anopheles sinensis. The infection rate of JEV in mosquitoes in Sanming, Jianyang
      and Fuzhou were 1.25%, 1.76% and 0.65%, respectively. One full genome in the
      positive specimens was sequenced. And further study showed that the positive JEV
      sequences belonged to genotype I. CONCLUSION: Genotype I Japanese encephalitis
      virus is the main genotype in mosquitos in Fujian province.

PMID- 23002539
TI  - [Molecular characteristics of the genome of G I of Japanese encephalitis virus
      isolated from the specimen collected from viral encephalitis case for the first
      time].
AB  - OBJECTIVE: To investigate the molecular basis of pathogenicity of Japanese
      encephalitis virus (JEV) by sequencing of complete nucleotide sequence and
      analyze the characteristics of full-length genome of genotype I Japanese
      encephalitis virus strains (GZ56) which was isolated from the first cerebrospinal
      fluid (CSF) of Japanese encephalitis patients. METHODS: The complete nucleotide
      sequence was obtained by RT-PCR and sequencing was performed directly.
      Bioinformatics was used to analyze the nucleic acid data, deduced amino acid
      sequence and phylogenetic trees. RESULTS: The result of sequence analysis showed
      that the genome of GZ56 strains had 10 965 nucleotides, which coded for a 3432
      amino acid polyprotein. Phyolngenetic analysis based on full-length genome showed
      that GZ56 strains and M-28 strains which were the first isolated from mosquitoes
      in Yunnan in 1977 were in the same evolutionary branch. GZ56 strains belongs to
      genotype I of Japanese encephalitis virus, the homology of genome ranged from
      96.2% to 98.6% in nucleotide and from 98.2% to 99.7% in amino acid sequences
      respectively when compared with selected genotype I of JEV strains in GenBank.
      There were 11 amino acid divergences in E protein when compared with the JEV
      inactivated P3 strain but they are not the key virulence sites. However, there
      were 14 amino acid divergences in E protein when compared with the JEV live
      attenuated vaccine SA14-14-2 strain and 8 amino acid divergences were the key
      virulence sites. CONCLUSION: This study indicated that the full length of genome
      GZ56 strains had no ignificant change. It can be hypothesized from genomic level
      that the currently available JEV vaccines(inactivated and live attenuated) can
      protect against GZ56 strains infection, meanwhile, the JEV live attenuated
      vaccine (SA14-14-2) formulation conferred higher levels of protection.

PMID- 23002540
TI  - [Gene optimization, protein expression, purification and characterization of the
      HDV antigen for diagnosis].
AB  - OBJECTIVE: To prepare HDAg with biological activities as a candidate of
      diagnostic reagent. METHODS: To synthesize HDV gene fragment after codon
      optimization. To construct a thio-fused recombinant plasmid based on M48
      expression vector. To express in E. coli induced by IPTG. To purify the protein
      by affinity chromatography followed by characterization in ELISA: RESULTS:
      Plasmid construction was verified by enzyme digestion. SDS-PAGE indicated the
      molecular weight of the protein was the same as we expectation. ELISA proved its
      affinity with HDV antibodies. CONCLUSION: HDAg was obtained successfully and it
      will pave the road to the research of HDV diagnostic reagent.

PMID- 23002541
TI  - [Relationship between mannose-binding protein gene polymorphisms and disease
      progression and HBV DNA in patients with chronic HBV infection].
AB  - OBJECTIVE: To determine the influences of Mannose binding protein (MBP) gene
      polymorphisms on HBV DNA loads and on the progression of liver disease in
      patients with chronic HBV infection. METHOD: The Codons on 54 MBP gene
      polymorphisms and HBV DNA loads in a cohort of 395 patients with chronic HBV
      infection, including 244 with chronic hepatitis B (CHB), 151 with liver cirrhosis
      (LC) and 88 normal controls were examined by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and fluorescent quantitative
      PCR (FQ-PCR). RESULT: The MBP genotype frequencies of GGC/GAC and alleles genetic
      frequencies of GAC in CHB group showed no significant differences comparing to
      the normal control group (P > 0.05). The MBP genotype frequencies of GGC/GAC and
      alleles genetic frequencies of GAC on CHB group (severe), compensation phase of
      LC group and decompensation phase of LC group were higher than those in the
      normal control group (P < 0.05), the genetic polymorphism of decompensation of LC
      was 36.5%, highest of all. The MBP genotype frequencies of GGC/GAC and alleles
      genetic frequencies of GAC of patients with chronic HBV infection were not
      changed with the differences of HBV-DNA loads. CONCLUSION: The codes on 54 MBP
      gene polymorphisms is not closely related to HBV DNA loads, but was associated
      with the progression of hepatitis B infection.

PMID- 23002542
TI  - [Cloning and eukaryotic expression of HIV-1B gp120 genes from a patient with AIDS
      dementia complex].
AB  - OBJECTIVE: To clone and express the HIV-1B gp120 genes isolated at different
      organizations from a patient died of AIDS dementia complex (ADC) in eukaryotic
      cells. METHODS: Using the genomic DNA isolated from peripheral lymphnodes,
      choroid plexus and occipital white matter from a patient died of ADC as the
      template, HIV-1B gp120 gene was amplified with PCR. After sequenced, HIV-1B gp120
      was inserted into pcDNA3.1 (+) and recombinant expressing vector gp120/pcDNA3.1
      (+) was constructed succeffuly confirming with sequencing. Then expressing vector
      was transfected into eukaryotic cells U87 using liposome transfection and
      expression of HIV-1B gp120 gene was assayed with indirect immunofluorescence.
      RESULTS: HIV-1B gp120 genes isolated from peripheral lymphnodes, choroid plexus
      and occipital white matter of the ADC patient were successfully cloned and
      recombinant expressing vector gp120/pcDNA3; 1 (+) could express envelope
      glycoprotein HIV-1B gp120 in U87 cells. CONCLUSION: All the HIV-1B gp120 gene
      isolated at the different organizations of the same ADC patient could express in
      U87 cells, which may supply a valuable basis for studying the neurotoxicity and
      neurotoxic mechanism of HIV-1 gp120 protein.

PMID- 23002543
TI  - [Characterization of hepatitis B virus antigen expression in vitro and in vivo
      transduced by different transfer plasmids carrying HBV infectious genome].
AB  - OBJECTIVE: To character HBV antigen expression in vitro and in vivo transduced by
      different transgenic plasmids carrying infectious genome of hepatitis B virus
      (HBV). METHODS: We constructed four different lentiviral transfer plasmids
      (carrying 1.3 full-length genome of HBV, by replacing the EGFP express box in pCS
      CG plasmid with HBV genome and with different structural element, named as pCS
      HBV1.3 (pCS-HBV1.3 X, pCS-HBV1.3 P, pCS-HBV1.3 N and pCS-HBV1.3 K). We detected
      the expression of HBsAg and HBeAg by ELISA in different time after transfected
      Huh 7 cells or hydrodynamic injection into C57 BL/6 mice with transfer plasmids
      pCS-HBV, respectively. RESULTS: We detected significant expression of HBsAg over
      5 days after transfected Huh 7 cells (in vitro) or hydrodynamic injection into
      C57 BL/6 mice (in vivo) with transfer plasmids pCS-HBV1.3 X, pCS-HBV1.3 P and pCS
      HBV1.3 K. The expression level and dynamics of HBsAg and HBeAg in the sera of
      mice is consistent with that of in the supernatant of Huh-7 cell. Furthermore,
      the expression of HBV antigens were modulated by the direction and position of
      HBV insert, also by some lentiviral vector cis-elements (cPPT and RRE).
      CONCLUSION: The optimal lentiviral transfer plasmids (pCS-HBV1.3 X, pCS-HBV1.3 P
      and pCS-HBV1.3 K) could be further used for establishment and application of HBV
      transgenic cell or animal model.

PMID- 23002544
TI  - [Molecular epidemiological and clinical feature of human metapneumovirus in
      children with acute lower respiratory tract infection in Changsha area from 2007
      to 2011].
AB  - OBJECTIVE: To understand the epidemiological characteristics of human
      metapneumovirus (hMPV) infection in children with acute lower respiratory tract
      infection (ALRTI) in Changsha area, China. METHODS: A total of 2613
      nasopharyngeal aspirate (NPA) specimens were collected from hospitalized children
      with ARTIs between September 2007 and February 2011 (a period of 3.5 years) in
      Changsha area, Hunan Province, China. Respiratory specimens were screened for
      hMPV M gene by reverse-transcription polymerase chain reaction (RT-PCR). All RT
      PCR positive' amplification products were confirmed by sequencing or analyzed and
      compared with those in GenBank known hMPV reference strain. RESULTS: hMPV was
      detected in 135 (5.2%) out of the 2613 children. The detected rate was
      significantly different between male and female (chi2 = 8.007, P = 0.003). The
      majority of the hMPV-positive patients (63.2%) were 0-1 year old infants. The
      majority of hMPV-positive patients were detected during spring season. Seasonal
      distribution showed that subtype A2b circulated predominantly in winter and
      spring, subtype B2 circulated predominantly in summer and spring. The most common
      genotype in 135 hMPV-positive patients were A and B in human subjects in
      Changsha. The predominant genotype of hMPV changed over the 3.5 year study period
      from genotype A2b to combined A2b and B2, and to B2. The 66 (48.9%) out of the
      135 hMPV-positive patients were found to be co-infected with other respiratory
      viruses, and human bocavirus (HBoV) was the most common additional respiratory
      virus. CONCLUSION: These data suggest that some cases of acute lower respiratory
      infection in young children in Changsha area are related to hMPV and the majority
      of children infected with hMPV were less than 1 years old, the detected rate of
      boys was higher than that of girls. It circulated predominantly in spring. The
      subtype A2b genetic lineage and the subtype B1 genetic lineage of hMPV were
      revealed alternately in human subjects in Changsha area and the hMPV exhibited
      high co-infection rate with other respiratory viruses.

PMID- 23002545
TI  - [Human enterovirus 71 (EV71) resisted type I interferon induced antiviral
      effect].
AB  - OBJECTIVE: To investigate human enterovirus 71 (EV71) resistance to type I
      interferon induced antiviral effect. METHODS: After type I interferons (alpha,
      beta) were incubated with HeLa cells, recombinant type I herpes simple virus (HSV
      1) with green fluorescent protein (GFP) was inoculated onto the HeLa cells. HSV-1
      proliferation was observed by GFP expression and PCR. After EV71 was inoculated
      onto HeLa cells incubated with the same quantity of interferon, proliferation of
      EV71 were detected by RT-PCR of 2A gene. RESULTS: Recombinant HSV-1 GFP
      expression and viral DNA replication obviously decreased in HeLa cells incubated
      with type I interferon (alpha, beta). However, EV71 effectively proliferated in
      the interferon irritated HeLa cell by RT-PCR. CONCLUSION: HeLa cell irritated by
      type I interferon (alpha, beta) produced antiviral substance that inhibits HSV-1
      proliferation. EV71 resisted the antiviral substance induced by type I interferon
      and could significantly replicate in the HeLa cells.

PMID- 23002546
TI  - [Effects of myxoma virus on gliomas of rats models in vivo].
AB  - OBJECTIVE: To explore the in vivo effects of myxoma virus (MV) on gliomas of rat
      model. Methods C6 glioma cells were implanted into the frontal lobe of SD rats
      using stereotactic methods to establish animal models of glioma. METHODS: C6
      glioma cells were implanted into the frontal lobe of SD rats using stereotactic
      methods to establish animal models of glioma. Models were divided into 4 groups
      randomly after tumor growth was affirmed, and MV, 5-FU, MV + 5-FU, and denatured
      myxoma virus (DV) were implanted into the tumors using stereotactic methods,
      bodyweight, tumor size, expression of glial fibrillary acidic protein (GFAP), Akt
      of each model were observed. RESULTS: The gliomas in all SD rats were established
      successfully. And tumor growth in MV, 5-FU, MV + 5-FU were significantly
      decreased as compared with DV group after injection, sizes of some tumors were
      lessened, and GFAP expression decreased in MV, 5-FU and MV +5-FU groups. The
      expression of PI3k, Akt and mTOR were decreased in MV and MV +5-FU groups.
      CONCLUSION: C6 glioma SD rat models could be established successfully using
      stereotactic methods. MV may enhance biological activity of chemotherapeutic
      drugs on tumor cells of animal models in vivo by regulating some genes of PI3K
      Akt-mTOR signal pathway.

PMID- 23002547
TI  - [Study on effects of kurarinol combined with glycyrrhizic acid on cellular
      immunity of patients with chronic hepatitis B].
AB  - OBJECTIVE: To explore effects of kurarinol combined with Diammonium
      Glycyrrhizinate on specific cellular immunity of patients with chronic hepatitis
      B (CHB). METHODS: Sixty-three CHB patients were randomly divided into two groups,
      32 cases in group of kurarinol combined with Diammonium Glycyrrhizinate group
      (combined therapy group) were treated with 600 mg kurarinol glucose injection
      intravenously, once a day for one month, then 200 mg kurarinol capsule was used
      orally, three times a day for two months. 150 mg Diammonium Glycyrrhizinate for
      Injection was added to 250 ml 10% glucose injection for intravenous drip, once a
      day for one month, then 150 mg Diammonium Glycyrrhizinate capsule was used
      orally, three times a day for two months; 31 case in kurarinol group (single drug
      group) only used kurarinol, methods and dosage were the same as those of
      treatment group. HBV specific CTL, T cell subgroups, change of Th1 and Th2 level,
      HBV-DNA and HBeAg negative rate of the two groups were compared. RESULTS: Three
      months after treatment, HBV specific CTL, CD4 + and Th1 of combined therapy group
      were higher than those before treatment, and higher than those of single drug
      group after treatment (P < 0.01). CONCLUSION: HBV-DNA and HBeAg negative rate
      between the two groups had no statistic significance (P > 0.05). CONCLUSION:
      Kurarinol combined with Diammonium Glycyrrhizinate can further increase HBV
      specific CTL, CD4+ and Th1 level of CHB patients.

PMID- 23002548
TI  - [A clinical study on leucogen tablets therapy efficacy during PEG-alpha
      interferon and alpha-interferon in chronic hepatitis B].
AB  - OBJECTIVE: To discuss the efficacy of Leucogen tablets treatment lessen the
      hematological reaction and raise the efficacy therapy of interferon in chronic
      hepatitis B treated with PEG-alpha interferon and alpha interferon. METHODS: A
      total of 395 patients with HBeAg-positive chronic hepatitis B (CHB) inpatients
      from January 2002 to February 2011. Group: All the patients were assigned to A or
      B according as during the treatment added Leucogen tablets or not. RESULTS: (1)
      All of 35.9% patients had neutrophil counts decrease under 1 x 10(9)/L, A group
      had 29.6%, B had 42.8% patients, P = 0.01; neutrophil counts < or = 0.75 x
      10(9)/L A group had 12.6% ,B group had 26.4%, P = 0.02; neutrophil counts < or =
      0. 5 x 10(9)/L A group had 4.8%, B group had 16.4%, P = 0.04. (2) A group had
      8.2% patients interferon-alpha dose decreased, all the patient finished the
      period of therapy. B group had 23.3% patients interferon-alpha dose decreased,
      2.1% of patients had paused. A group had 40.3% of patients interferon-alpha
      beyond conventional dose, B group had only 5.2%. (3) All of 9.8% patients had
      hematoblast decrease under 100 x 10(9)/L, A group had 8.7%, B had 11.1% patients;
      hematoblast < or = 80 x 10(9)/L A group had 5.3%, B group had 7.9%; hematoblast <
      or = 50 x 10(9)/L A group had 1.0%, B group had 2.6%. A group had the trend of
      reducing hematoblast decrease. (4) At the end of therapy A group had 67.4%
      patients HBVDNA < 100IU/ml, 54.3% e antigen negative, 40.7% e antigen conversed;
      B group had 53.9%, 41.2%, 26.9%, P was respectively 0.02, 0.01, 0.01. CONCLUSION:
      Leucogen tablets treatment and prevention interferon-alpha-related neutrophil
      counts hematological reaction in CHB treated with alpha-interferon, and had the
      trend of reducing interferon-alpha-related hematoblast decrease, farther improved
      the efficacy of alpha-interferon treatment CHB.

PMID- 23002550
TI  - [Prevalence and clinical characteristics of thyroid disease induced by chronic
      hepatitis B treated with polyethylene glycol (peg) interferon-alpha].
AB  - OBJECTIVE: To study the prevalence and clinical characteristics of thyroid
      disease induced by chronic hepatitis B treated with polyethylene glycol (peg)
      interferon-alpha. METHODS: Totally 210 patients with chronic hepatitis B were
      monitored for thyroid function and thyroid antibodies before application of
      polyethylene glycol (peg) interferon-alpha therapy and every 3 months during and
      after the treatment. RESULTS: After treatment with polyethylene glycol (peg)
      interferon-alpha, 6.7% (14/210) of patients had thyroid disease, in which 5.2%
      (11/210) had hyperthyroidism and 1.4% (3/210) had hypothyroidism. The proportion
      of the hyperthyroidism and hypothyroidism in women were 11.8% (6/51) and 3.9%
      (2/51), higher than 3.1% (5/159) and 0.6% (1/159) in male (P < 0.05). In women
      subjects, higher proportion of those who developed thyroid disease were positive
      for antibody against thyroid peroxidase (TPOAb) before treatment and positive for
      antibody against thyroid globulin (TgAb) during the treatment as compared with
      those who did not develop thyroid disease (P < 0.05). CONCLUSION: Patients with
      chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha
      therapy are prone to develop thyroid disease. Women positive for TPOAb and TgAb
      may be at increased risk for developing thyroid disease.

PMID- 23002549
TI  - [Efficacy of combination therapy with peginterferon alfa-2alpha and bicyclol in
      chronic hepatitis B with high ALT levels].
AB  - OBJECTIVE: To evaluate the effect of combination therapy with peginterferon alfa
      2a (Pegasys) +/- nucleos(t)ide analogues (NUC) and bicyclol in chronic hepatitis
      B with high ALT levels at baseline and during early treatment. METHODS: CHB
      patients were treated with PEG-IFNalpha-2a for a minimum of 48 weeks. All
      patients were followed up for 26 weeks post-treatment. Patients with HBV DNA > or
      = 1 x 10(8) copies/ml were combined with NUC (adefovir or entecavir) treatment.
      Patients with ALT > 500 U/L at baseline or ALT > 300 U/L after first injection of
      PEG-IFNalpha-2a received bicyclol treatment for 1-2 months (treatment group).
      Patients with 2 x ULN < ALT < 300 U/L and ALT < 300 U/L during treatment were
      enrolled into PEG-IFNalpha-2a +/- NUC antiviral monotherapy (control group).
      Responses defined as HBV DNA < 1 x 10(3) copies/ml, normal serum ALT, and
      HBeAg/HBsAg loss and seroconversion were analyzed at 26 weeks post-treatment.
      RESULTS: A total of 54 patients (44 HBeAg positive, 10 HBeAg negative) were
      divided into two groups according to combination of bicyclol: treatment group (n
      = 20)--those who received combinition therapy with PEG-IFNalpha-2a +/- NUC and
      bicyclol, and control group (n = 34)--those who were treated with PEG-IFNalpha-2a
      +/- NUC antiviral monotherapy. During the first month of treatment, ALT levels
      declined gradually in treatment group. At 26 weeks post-treatment, the rates of
      ALT normalization and HBV DNA below the limit of 1 x 10(3) copies/ml were similar
      in both groups. Six patients in treatment group achieved HBsAg seroconversion at
      26 weeks post-treatment, whereas so did 4 patients of control group (30% vs.
      11.8%, P = 0.044). CONCLUSION: Bicyclol could significantly relief elevation of
      ALT induced by the IFN treatment.

PMID- 23002551
TI  - [Involvement of dendritic cells frequency and function in outcomes of interferon
      alpha therapy for chronic hepatitis B patients].
AB  - OBJECTIVE: To elucidate the change in frequencies and functions of myeloid
      dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) before and after
      interferon-alpha therapy for chronic hepatitis B (CHB) patients, and its
      correlation with virological and biochemical data. METHODS: Thirty patients with
      HBeAg-positive CHB who underwent IFN-alpha therapy were examined. Frequencies and
      expression of CD86 of mDC and pDC of peripheral blood were measured at baseline
      and treatment week (TW) 12 by flow cytometry. According to biochemical and
      virological parameters, the 30 patients were divided into ALT normalized group,
      ALT non-normalized group and virological responder group, virological non
      responder group respectively. Statistical analysis of DC changes among different
      groups at baseline and TW12 was proceeded. RESULTS: (1) In the ALT normalized
      group, the pDC frequency at TW12 (0.25 +/- 0.14%) was higher than that at
      baseline (0.18 +/- 0.09%) (P = 0.023); in the ALT non-normalized group, the mDC
      frequency (0.58 +/- 0.34%) and its surface CD86 expression (61.80 +/- 22.52%)
      decreased significantly as compared with baseline (0.88 +/- 0.51%, 79.92 +/-
      25.94%, respectively), (P = 0.025, P = 0.036, respectively). (2) In the
      virological responder group, the CD86 expression on pDC at TW12 (46.86 +/-
      12.22%) was higher than that at baseline (29.42 +/- 15.16%) (P = 0.002); in the
      virological non-responder group, the mDC frequency (0.51 +/- 0.22%) and its
      surface CD86 expression (59.63 +/- 22.94% ) decreased significantly as compared
      with baseline (0.94 +/- 0.58%, 80.11 +/- 29.34%, respectively), (P = 0.006; P =
      0.049, respectively). CONCLUSION: In IFN-alpha therapy for CHB patients, the
      increments of pDC frequency and function were related to biochemical and viral
      response, and decreases of mDC frequency and function were related to non
      biochemical and non-viral response.

PMID- 23002552
TI  - [Determination of serum IL-23 and its significance in patients with severe
      chronic hepatitis B].
AB  - OBJECTIVE: To investigate the level of the serum IL-23 and its correlation with
      serum biochemical indices of liver function tests and HBV DNA load in patients
      with chronic severe hepatitis B. METHODS: Fifty patients with chronic severe
      hepatitis B (severe hepatitis group) and 18 healthy controls (control group) were
      enrolled in the study. The serum IL-23 expression level was detected by ELISA
      method. The correlation between IL-23 and ALT, AST, TBil, HBV DNA load was
      analyzed using Pearson's correlation analysis, respectively. RESULTS: Serum IL-23
      expression level in severe hepatitis group was significantly higher than that of
      control group (P < 0.05). Serum IL-23 level was positively correlated with serum
      ALT, AST, respectively (P < 0.05), but was not correlated with TBil and HBV DNA
      load, respectively (P > 0.05). CONCLUSION: Serum IL-23 expression level was
      increased in patients with chronic severe hepatitis B and was associated with the
      severe of inflammation. We, therefore, believe that IL-23 might be involved in
      the pathogenesis of chronic severe hepatitis B.

PMID- 23002554
TI  - [Prognostic analysis and establishment of a prognostic model for patients with
      liver failure with hepatorenal syndrome].
AB  - OBJECTIVE: To identify the factors that may influence the prognosis of patients
      with hepatorenal syndrome and try to establish a prognostic model. METHODS: Data
      of 126 patients with hepatorenal syndrome were analyzed and 56 indexes that might
      affect the prognosis were focused on, involving history, symptoms, signs and lab
      findings. Cox model and Kaplan-Meier survival analysis were used. RESULTS: Many
      factors were found to affect the prognosis independently, including hepatic
      encephalopathy (HE) and its degree, gastrointestinal bleeding (GIB), blood
      neutrophil count (N1) and serum creatinine (Cr). The prognosis model was
      established as the following equation where PI represents prognosis index: PI =
      0.711HE + 0.836GIB + 0.052N1 + 0.002Cr (GIB: no = 0, yes = 1; HE: no = 0, phase I
      = 1, phase II = 2, phase II = 3, phase IV = 4). When PI < 1, the average survival
      time was 42 days; when 1 < or = PI < or = 3, the average survival time was 15
      days; when PI > 3, the average survival time was 2 days. CONCLUSION: The results
      obtained from this study may help in estimation of diagnosis, analysis of illness
      state and evaluation of therapy in clinical work.

PMID- 23002553
TI  - [Prognostic value of brain natriuretic peptide in people with viral myocarditis].
AB  - OBJECTIVE: To explore the brain natriuretic peptide (BNP) on prognostic value in
      patients with viral myocarditis. METHODS: A total of 48 patients with viral
      myocarditis and 42 healthy people were enrolled and followed up for two years.
      The NYHA class and LVEF were recorded and the concentration of BNP were measured.
      RESULTS: The concentration of BNP were higher and EF were lower in patients with
      viral myocarditis (P < 0.01) than contrast people. Higher levels of plasma BNP
      were related to higher mortality. CONCLUSION: Levels of brain natriuretic peptide
      measured in the plasma could be a useful biochemical marker for the myocarditis,
      and high concentration of BNP may correlate with poor prognosis in patients with
      myocarditis.

PMID- 23002555
TI  - [The antiviral role of Toll-like receptor 3 in human lung epithelial cells
      infected with respiratory syncytial virus].
AB  - OBJECTIVE: In order to understand the production mechanism of interferon and
      provide a scientific basis for preventionand clinical therapy, the expression
      changes of Toll-like receptor (TLR3) mRNA and the role of TLR3 in human lung
      epithelial cells (A549 cells) infected with respiratory syncytial virus (RSV)
      were investigated in this study. METHODS: RSV infected A549 cells were treated
      with or without specific antibodies of TLR3 and collected at the selected
      timepoints after RSV infection (4, 8, 12, 16 and 24h). The expressions of TLR3,
      IFN-alpha, IFN-beta and RSV F mRNA were evaluated by RT-PCR. RESULT: It was found
      that RSV infection could markedly up-regulate the mRNA expression of TLR3, IFN
      alpha, IFN-beta and RSV F protein in a time-dependent manner as the 24h mRNA
      expressions of them were 4 times, 3 times, 3 times and 0.7 times more than the
      basic expression, respectively. Treatment of TLR3 specific antibodies, whereas,
      significantly down-regulated the activation of TLR3. The mRNA expression of IFN
      alpha and IFN-1beta also decreased accordingly and that of IFN-beta reduced more
      obviously than IFN-alpha, but that of RSV F protein rose significantly.
      CONCLUSION: Above data indicate that RSV infection could induce an apparent
      increase of antiviral genes of IFN-alpha and IFN-beta by activating TLR3 in human
      lung epithelial cells and the activated cells mediated Type I interferon is
      antiviral, which suggesting that TLR3 might play an important role in antiviral
      activity of RSV-infected human lung epithelial cells.

PMID- 23002556
TI  - [Prevalence and clinical characteristics of coronavirus NL63 infection in
      children hospitalized for acute lower respiratory tract infections in Changsha].
AB  - OBJECTIVE: The main objective of this study was to explore the prevalence and
      clinical characteristics of human coronavirus NL63 infection in hospitalized
      children with acute lower respiratory tract infection (ALRTI) in Changsha.
      METHODS: Nasopharyngeal aspirates (NPA) samples were collected from 1185
      hospitalized children with ALRTI at the People's Hospital of Hunan province,
      between September 2008 and October 2010. Reverse transcriptase polymerase chain
      reaction (RT-PCR) was employed to screen for coronavirus NL63, which is a 255 bp
      fragment of a part of N gene. All positive amplification products were confirmed
      by sequencing and compared with those in GenBank. RESULTS: The overall frequency
      of coronavirus NL63 infection was 0.8%, 6 (60%) out of the coronavirus NL63
      positive patients were detected in summer, 2 in autumn, 1 in spring and winter,
      respectively. The patients were from 2 months to two and a half years old. The
      clinical diagnosis was bronchopneumonia (60%), bronchiolitis (30%), and acute
      laryngotracheal bronchitis (10%). Four of the 10 cases had critical illness, 4
      cases had underlying diseases, and 7 cases had mixed infection with other
      viruses. The homogeneity of coronavirus NL63 with those published in the GenBank
      at nucleotide levels was 97%-100%. CONCLUSION: Coronavirus NL63 infection exists
      in hospitalized children with acute lower respiratory tract infection in
      Changsha. Coronavirus NL63 infections are common in children under 3 years of
      age. There is significant difference in the infection rate between the boys and
      the girls: the boys had higher rate than the girls. The peak of prevalence of the
      coronavirus NL63 was in summer. A single genetic lineage of coronavirus NL63 was
      revealed in human subjects in Changsha. Coronavirus NL63 may also be one of the
      lower respiratory pathogen in China.

PMID- 23002557
TI  - [Preparation and identification of a recombinant hepatitis C virus (HCV) based on
      sindbis virus vector].
AB  - OBJECTIVE: To construct the recombinant virus-like particles containing HCV
      envelope glycoprotein E1E2 based on sindbis virus vector. METHODS: The gene
      encoding HCV envelope glycoprotein E1E2 was cloned into sindbis virus vector to
      construct recombinant plasmids pBR-XJE1E2 and pVA-XJE1E2, and transfect them into
      BHK-21 cells to obtain recombinant virus-like particles. The expression of E1 and
      E2 protein were verified by Western Blot and indirect immunofluorescent assay
      (IFA). RESULTS: The results of restriction enzyme digestion, PCR and sequencing
      analysis showed that the recombinant plasmids were constructed successfully. And
      the results of RT-PCR, Western blotting and IFA detection showed that the
      transfect cells could package HCV-like particles of expressing structural
      proteins E1E2. CONCLUSION: The recombinant expression plasmids pBR-XJE1E2 and pVA
      XJE1E2 based on sindbis virus vector could package HCV-like particles in
      eukaryotic cell, which provides a foundation for further study of its in vivo
      animal immune response.

PMID- 23002558
TI  - [Primary establishment of an alphaLISA assay for detection of HAV IgM].
AB  - OBJECTIVE: To develop an AlphaLISA method for detection of antibody of Hepatitis
      A virus. METHODS: After hepatitis A virus antigen was concentrated and
      biotinylated, optimal biotinylated HAV antigen, donor bead, acceptor bead
      concentration have been explored and determined by both dot-blotting and
      AlphaLISA methods. 97 samples including 23 serums from patients HAV infected and
      70 serums from blood donors have been detected by new AlphaLISA method. RESULTS:
      The sensitivity and specificity for anti-HAV IgM were 78% and 98.5%, the positive
      and negative predictive value were 95% and 93%. CONCLUSION: A homogeneous and
      fast AlphaLISA assay for detection of HAV IgM has been established by preliminary
      verification on samples.

PMID- 23002559
TI  - [Establishment and application of TaqMan real-time RT-PCR for the detection of
      hepatitis A virus].
AB  - OBJECTIVE: To establish a specific TaqMan-based Real-time PCR assay for the
      detection of hepatitis A virus in serum samples. METHODS: According to the
      references, primers-probe sets which were located in 5'-NCR, the most
      conservative part of HAV genome were designed and therefore we established a
      TaqMan real-time RT-PCR assay with great performance of specificity, sensitivity
      and reproducibility. And then it was used in the detection of HAV RNA in serum
      from HAV patients. RESULTS: The HAV Real-time RT-PCR assay established in this
      study were able to detect HAV RNA and its detection limit ranged from
      0.1CCID50/reaction to 0.01CCID50/reaction. When the detection of a same sample
      was repeated for three times, coefficients of varistion (CV) of intra- and inter
      assay were calculated and they were all less than 2.0% and 2.6% respectively. Our
      data suggested that there were 5.18 x 10(2) - 4.93 x 10(7) RNA copies in 1 ml of
      the serum from acute HAV patients. CONCLUSION: The TaqMan-based Real-time PCR
      assay established in this study was specific and precise for the rapid detection
      of HAV RNA. It was applied successfully in the pathogen detection of clinical
      samples.

PMID- 23002560
TI  - [Acoustic radiation force impulse for evaluation of hepatic fibrosis and early
      stage cirrhosis].
AB  - OBJECTIVE: To investigate the value of acoustic radiation force impulse (ARFI) in
      evaluating the stage of hepatic fibrosis and early stage cirrhosis. METHODS:
      Sixty-six patients with viral hepatitis underwent liver biopsy and 33 normal
      subjects (S0) were selected to accept ARFI,the shear wave velocity of hepatic
      segments s5, s6, s7, s8 and size of liver were measured. The results of liver and
      spleen size and portal vein's diameter were also measured. RESULTS: The 66
      patients were divided into 3 groups: S1, S2-S3, S4. ARFI for 66 patients and 33
      normal subjects showed good image quality. There were statistically significant
      differences between S4 group and S0 group, S1 group, S2-S3 group for the shear
      wave velocity of hepatic segments s5, s6, s7, s8 (P < 0.05). Between S2-S3 group
      and SO group S1 group, the shear wave velocity of hepatic segments s5, s6, s7, s8
      also have statistically significant differences (P < 0.05), other parameters
      showed no significant difference (P > 0.05). Spleen size and the portal vein's
      diameter of S4 group were larger than those in other groups (P < 0.05).
      CONCLUSIONS: The invasive acoustic radiation force impulse could evaluate the
      stage of hepatic fibrosis and early stage cirrhosis in patients suffering from
      viral hepatitis. The measurement was feasible. It was suitable for clinical use.

PMID- 23002561
TI  - [Value of combined detection of GP73 and alpha-fetoprotein in diagonosis of
      hepatocellular carcinoma].
AB  - OBJECTIVE: To explore the diagnostic value of the measurement of serum Golgi
      protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC). METHODS:
      Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum GP73 in
      the 81 cases of HCC, 71 cases of chronic hepatitis or cirrhosis (CH/LC) and 65
      cases of healthy blood donors, and to evaluate the sensitivity and specificity in
      the diagnosis of HCC through the ROC curves. RESULTS: The average levels of serum
      GP73 in HCC, CH/LC and Normal groups were (152.67 +/- 33.59) ng/ml, (93.15 +/-
      20.02) ng/ml and (58.95 +/- 17.29) ng/ml(o) After calculating through the ROC
      curves, 120 ng/ml was set as the optimal cut-off point, GP73 has a sensitivity of
      77.80% and a specificity of 78.00%. CONCLUSIONS: GP73 as a serum marker in the
      diagnosis of HCC had a higher sensitivity than AFP, and the combined detection of
      GP73 and AFP could improve HCC diagnosis.

PMID- 23002562
TI  - [Detection of WU polyomavirus in children with low respiratory tract infections
      using real-time fluorescent quantitative PCR].
AB  - OBJECTIVE: Development and application of a real time fluorescent quantitative
      PCR (FQ-PCR) assay for detecting WU polyomavirus in children with low respiratory
      tract infections. METHODS: The VP2 gene of WU polyomavirus was selected as the
      detection target, from which the real time primers and probes were designed. The
      standard curve was established by using recombinant plasmid as template. And the
      FQ-PCR assay for specific detection of WU polyomavirus was established. The
      specificity, sensitivity and reproducibility of the method were evaluated.
      Furthermore, the clinical specimens from children with respiratory tract
      infections collected in Wenling First People's Hospital were quantitatively
      detected using this method. RESULTS: In this study, the FQ-PCR method was
      established to detect a specific fragment in VP2gene of WU polyomavirus. The
      standard curve coefficient R2 was 0.998. And this method can detect as low as 50
      copies recombinant plasmid. The clinical specimens of sputum and throat swab from
      children with respiratory tract infections were quantitatively detected using
      this method. 7 sputum specimens were detected as WU polyomavirus positive in 700
      sputum specimens, the positive ratio was 1.00%. No positive specimens were
      detected in 146 specimens of throat swabs and 846 blood samples from same patient
      population. CONCLUSION: The results indicated that the FQ-PCR assay method
      established in this study was specific, rapid and sensitive for detecting WU
      polyomavirus in children with lower respiratory tract infections. The sputum
      specimen is more suitable to be used for gene detection of WU polyomavirus than
      throat swab or blood.

PMID- 23002563
TI  - The role of the C-suite in the incorporation of evidence-based design in
      healthcare construction.

PMID- 23002564
TI  - How to help hospitals achieve their mission through good design.
AB  - In 2003, Princeton HealthCare System (PHCS) completed a strategic plan that
      called for replacing its 220-bed acute care hospital--a decision driven by the
      need to serve a growing and aging population and the demand for new programs,
      services, technologies, and clinical strategies. As hospitals nationwide
      undertake similar projects to replace aging facilities, they face many of the
      same challenges. Various factors must be considered when designing a new
      hospital. Two significant obstacles to great design exist: First, hospital
      executives understand the economic and clinical drivers that affect hospital care
      and financial performance but often lack an appreciation for how design decisions
      can impact these critical factors. Second, CEOs often delegate oversight to
      others in the organization. The CEO's direct participation is necessary to ensure
      that the project reflects the organization's values and strategic and operational
      objectives. Solutions to address this dilemma include increased use of evidence
      based design and strategies such as tying payment for design services to long
      term facility performance indicators. Effective partnerships among healthcare
      planners, facility designers, and hospital executives will result in a new
      facility whose design promotes improved clinical outcomes, greater patient
      satisfaction, and financial viability.

PMID- 23002565
TI  - Building the "fable hospital"--the CEO's perspective: an interview with Michael
      H. Covert, president and chief executive officer, Palomar Pomerado Health.
      Interview by David A Tam.
AB  - Hospital construction is a significant event in any health system. The financial
      implications are great, especially at a time of shrinking capital resources.
      Personnel are affected, as are the processes to perform their tasks. Often, new
      facilities are catalysts that change organizational culture; it has been clearly
      shown that new facilities have a positive impact on patient satisfaction scores.
      The members of the C-suite of a hospital/health system play important roles in
      construction projects. However, no one is more critical to the success of such
      major endeavors than the chief executive officer (CEO). The CEO sets the tone for
      the project, giving direction to the design and construction process that may
      have implications for the rest of the organization. Palomar Pomerado Health (PPH)
      is the largest public health district in California. In 2002, the PPH governing
      board authorized the creation of a new facility master plan for the district,
      which included the construction of a replacement facility for its tertiary care
      trauma center. The new Palomar Medical Center is slated to open in August 2012.
      HERD had the opportunity to speak with PPH CEO Michael H. Covert on the role of
      the CEO in the building of this "fable hospital".

PMID- 23002566
TI  - C-suite executives: leading the design process from vision to post-occupancy.

PMID- 23002567
TI  - Using data to drive emergency department design: a metasynthesis.
AB  - OBJECTIVE: There has been an uptick in the field of emergency department (ED)
      operations research and data gathering, both published and unpublished. This new
      information has implications for ED design. The specialty suffers from an
      inability to have these innovations reach frontline practitioners, let alone
      design professionals and architects. This paper is an attempt to synthesize for
      design professionals the growing data regarding ED operations. METHODS: The
      following sources were used to capture and summarize the research and data
      collections available regarding ED operations: the Emergency Department
      Benchmarking Alliance database; a literature search using both PubMed and Google
      Scholar search engines; and data presented at conferences and proceedings.
      RESULTS: Critical information that affects ED design strategies is summarized,
      organized, and presented. Data suggest an optimal size for ED functional units.
      The now-recognized arrival and census curves for the ED suggest a department that
      expands and contracts in response to changing census. Operational improvements
      have been dearly identified and are grouped into three categories: input,
      throughput, and outflow. Applications of this information are suggested.
      CONCLUSION: The sentinel premise of this meta-synthesis is that data derived from
      improvement work in the area of ED operations has applications for ED design. EDs
      can optimize their functioning by marrying good processes and operations to good
      design. This review paper is an attempt to bring this new information to the
      attention of the multidisciplinary team of architects, designers, and clinicians.

PMID- 23002568
TI  - Using clinical simulation centers to test design interventions: a pilot study of
      lighting and color modifications.
AB  - OBJECTIVE: The aim of this pilot study was to test design interventions such as
      lighting, color, and spatial color patterning on nurses' stress, alertness, and
      satisfaction, and to provide an example of how clinical simulation centers can be
      used to conduct research. BACKGROUND: The application of evidence-based design
      research in healthcare settings requires a transdisciplinary approach.
      Integrating approaches from multiple fields in real-life settings often proves
      time consuming and experimentally difficult. However, forums for collaboration
      such as clinical simulation centers may offer a solution. In these settings,
      identical operating and patient rooms are used to deliver simulated patient care
      scenarios using automated mannequins. METHODS: Two identical rooms were modified
      in the clinical simulation center. Nurses spent 30 minutes in each room
      performing simulated cardiac resuscitation. Subjective measures of nurses'
      stress, alertness, and satisfaction were collected and compared between settings
      and across time using matched-pair t-test analysis. RESULTS: Nurses reported
      feeling less stressed after exposure to the experimental room than nurses who
      were exposed to the control room (2.22, p = .03). Scores post-session indicated a
      significant reduction in stress and an increase in alertness after exposure to
      the experimental room as compared to the control room, with significance levels
      below .10. (Change in stress scores: 3.44, p = .069); (change in alertness
      scores: 3.6, p = .071). CONCLUSION: This study reinforces the use of validated
      survey tools to measure stress, alertness, and satisfaction. Results support
      human-centered design approaches by evaluating the effect on nurses in an
      experimental setting.

PMID- 23002569
TI  - The challenge of innovation and the high-performance team.
AB  - PURPOSE: This paper describes the use of a high-performance team model in the
      leadership of a healthcare construction project with a vision of fostering
      innovation in the design and building process. This model facilitated the
      effective implementation of = Lean principles and a joint governance model
      combining stakeholders under a shared vision. BACKGROUND: The healthcare facility
      discussed is a California healthcare district in San Diego. Because of state
      seismic safety legislation, the district elected to build a replacement hospital
      for its tertiary care trauma facility. The organization's leadership decided to
      pursue a course that demanded innovation in both the design and construction
      process. The owner, architects, construction manager, and trade contractors
      adopted a high-performance team model to meet this challenge. CONCLUSIONS AND
      RECOMMENDATIONS: The governance and leadership of a construction project should
      reflect the design and ultimate intent of the facility. The vision of building
      the most innovative hospital under constrained resources required the
      implementation of an innovative approach to leading the construction process.

PMID- 23002570
TI  - Development of the Content and Quality in Briefs Instrument (CQB-I).
AB  - OBJECTIVE: The Content and Quality in Briefs Instrument (CQB-I) was designed to
      develop a valid and reliable audit instrument to examine the content and quality
      of information in documents (briefs) created in the early stages of designing
      healthcare environments. BACKGROUND: The importance of effective briefing has
      been emphasized in many research studies during the past two decades. However,
      there is no developed instrument for auditing the content and quality of these
      documents. METHODS: The study had a methodological and developmental design based
      on an established methodology for instrument development and validation. The
      development process consisted of three main phases: (1) item generation and scale
      construction; (2) assessment of face and content validity, and (3) testing of the
      reliability. To obtain face and content validity, expert panels reviewed the COB
      I. Content validity was assessed using the Content Validity Index (I - CVI = item
      level, S - CVI = scale level). Reliability was tested by test-retest and inter
      rater reliability. RESULTS: CQB-I was found to have good content validity (I -
      CVI = 0.78 - 1.0 and S - CVI = 0.98). Inter-rater reliability was acceptable
      (Spearman's correlation = 0.62) and stability was considered high for both raters
      (83% and 88%, respectively).

PMID- 23002571
TI  - Innovation pilot study: acute care for elderly unit--promoting patient-centric
      care.
AB  - PURPOSE: Older patients, defined as age 65 years or older, comprise more than 40%
      of admissions to the acute care environment. These patients' needs are different;
      cognitive impairment, chronic health issues, caregiver burden, and maintenance of
      functional level present challenges to healthcare organizations when caring for
      this population on a general medical-surgical unit. BACKGROUND: A pilot project,
      the creation of a six-bed Acute Care for Elderly (ACE) unit situated within a 33
      bed medical-surgical unit, was established to meet the unique needs of this older
      patient population. CONCLUSIONS: Outcomes including falls, pressure ulcers,
      functional level (the latter as measured by the KATZ), and length of stay were
      examined and demonstrated marked improvement compared to similar patients outside
      the ACE unit. Older patients need individualized care planning by staff competent
      in elder care and a specialty unit to address their specific needs.

PMID- 23002572
TI  - A cottage model for eldercare.
AB  - OBJECTIVE: An overview of medical, cognitive, and affective changes experienced
      by geriatric long-term care residents during a migration from traditional
      healthcare delivery to a cottage-based model. BACKGROUND: New architectural
      models hold great promise for improving health and social outcomes for residents.
      New studies must explore the resident, family, and staff outcomes across
      transformations, as well as the business case for change. METHODS: A
      longitudinal, quasi-experimental design was employed, with an emphasis on
      regularly acquired institutional data, including the Minimum Data Set, as well as
      commonly available survey instruments including the MOSES, the 2005 NSWHN, and
      Castle's Job Satisfaction Questionnaire. Descriptive statistics, McNemar's Exact
      Test, repeated measures ANOVA, and t-tests were used as well as narratives from
      families, staff, and management. RESULTS: Staff perceived enhanced institutional
      respect (t(72) = 2.38, p = 0.02) and work environment, and families perceived
      more staff cooperation and a better bond between staff and residents. No changes
      were discerned in a resident's prevalence of pain (odds ratio 0.43, p = .34, 95%
      CI [0.07, 1.88]), mobility (odds ratio 0.50, p =.19, 95% CI [0.17, 1.32]), range
      of motion(odds ratio 0.57, p = .55, 95% CI [0.12, 2.25]), or depression and
      anxiety (odds ratio 2.33, p =.11,95% CI [0.84, 7.41]). A modest decline in
      residents' systolic (t(101) = 3.74, p < .001) and diastolic (t(101) = 2.870, p <
      .01) blood pressures was demonstrated. The rate at which a resident's Activities
      of Daily Living score declined was attenuated (t(57) = 3.37, p < .001).
      Operational costs remained constant across the move. CONCLUSIONS: Cottage
      settings were aesthetically appealing to residents, family, and staff. Modest
      improvements in health outcomes were observed, and operational costs remained
      stable.

PMID- 23002573
TI  - Making acuity-adaptable units work: lessons from the field.
AB  - OBJECTIVE: Because there have been no clear directions on how to implement acuity
      adaptable units (AAUs), this paper describes actual tactics and strategies that
      have worked in multiple institutions. BACKGROUND: AAUs have been used in
      hospitals for the past decade, but reports in the literature have indicated both
      successes and difficulties in meeting operational goals and objectives. Despite
      various views regarding acuity adaptability, there is little in the literature
      that suggests why it works in some hospitals and not in others. METHOD: As part
      of a larger construction project, this project team interviewed the leaders of
      six hospitals to determine what was associated with the successful implementation
      of AAUs. RESULTS: This paper reports on themes that emerged from these
      interviews, namely: choose the right specialty for medical centers; adopt the AAU
      model for the entire facility in community hospitals; bring in and train the
      right people; change culture through communication; and use acuity-adaptable unit
      clusters. DISCUSSION AND CONCLUSIONS: Main themes, predictable patient progress,
      and culture change are further discussed and key recommendations are described.

PMID- 23002574
TI  - The moral responsibility of leadership for design outcome.

PMID- 23002576
TI  - Designing and building a new hospital or a major renovation.

PMID- 23002575
TI  - Simulation and mock-up research methods to enhance design decision making.

PMID- 23002577
TI  - The current challenges facing the healthcare system are well documented.

PMID- 23002578
TI  - Science, expertise, and democracy.
AB  - The combination of government's significant involvement in science, science's
      significant effects on the public, and public ignorance (of both politics and
      science) raise important challenges for reconciling scientific expertise with
      democratic governance. Nevertheless, there have recently been a variety of
      encouraging efforts to make scientific activity more responsive to social values
      and to develop citizens' capacity to engage in more effective democratic
      governance of science. This essay introduces a special issue of the Kennedy
      Institute of Ethics Journal, "Science, Expertise, and Democracy," consisting of
      five papers that developed from the inaugural Three Rivers Philosophy conference
      held at the University of South Carolina in April 2011. The pieces range from a
      general analysis of the in-principle compatibility of scientific expertise and
      democracy to much more concrete studies of the intersection between scientific
      practices and democratic values in areas such as weight-of-evidence analysis,
      climate science, and studies of locally undesirable land uses.

PMID- 23002579
TI  - Relying on experts as we reason together.
AB  - In various contexts, it is thought to be important that we reason together. For
      instance, an attractive conception of democracy requires that citizens reach
      lawmaking decisions by reasoning with one another. Reasoning requires that
      reasoners survey the considerations that they take to be reasons, proceed by a
      coherent train of thought, and reach conclusions freely. De facto reliance on
      experts threatens the possibility of collective reasoning by making some reasons
      collectively unsurveyable, raising questions about the coherence of the resulting
      train of thought. De jure reliance on experts threatens the possibility of
      collective reasoning by seeming to make some conclusions irreversible. The paper
      argues that collective reasoning that relies on experts would nonetheless be
      possible if the unsurveyable reasons "mesh," if the expert considerations are at
      least in principle publicly recoverable, and if de jure authority of expert
      decision is always subject to appeal.

PMID- 23002580
TI  - Values and uncertainties in the predictions of global climate models.
AB  - Over the last several years, there has been an explosion of interest and
      attention devoted to the problem of Uncertainty Quantification (UQ) in climate
      science-that is, to giving quantitative estimates of the degree of uncertainty
      associated with the predictions of global and regional climate models. The
      technical challenges associated with this project are formidable, and so the
      statistical community has understandably devoted itself primarily to overcoming
      them. But even as these technical challenges are being met, a number of
      persistent conceptual difficulties remain. So why is UQ so important in climate
      science? UQ, I would like to argue, is first and foremost a tool for
      communicating knowledge from experts to policy makers in a way that is meant to
      be free from the influence of social and ethical values. But the standard ways of
      using probabilities to separate ethical and social values from scientific
      practice cannot be applied in a great deal of climate modeling, because the roles
      of values in creating the models cannot be discerned after the fact-the models
      are too complex and the result of too much distributed epistemic labor. I argue,
      therefore, that typical approaches for handling ethical/social values in science
      do not work well here.

PMID- 23002582
TI  - Environmental justice, values, and scientific expertise.
AB  - This essay compares two philosophical proposals concerning the relation between
      values and science, both of which reject the value-free ideal but nevertheless
      place restrictions on how values and science should interact. The first of these
      proposals relies on a distinction between the direct and indirect roles of
      values, while the second emphasizes instead a distinction between epistemic and
      nonepistemic values. We consider these two proposals in connection with a case
      study of disputed research on the topic of environmental justice and argue that
      the second proposal has several advantages over the first.

PMID- 23002581
TI  - Weighing complex evidence in a democratic society.
AB  - Weighing complex sets of evidence (i.e., from multiple disciplines and often
      divergent in implications) is increasingly central to properly informed decision
      making. Determining "where the weight of evidence lies" is essential both for
      making maximal use of available evidence and figuring out what to make of such
      evidence. Weighing evidence in this sense requires an approach that can handle a
      wide range of evidential sources (completeness), that can combine the evidence
      with rigor, and that can do so in a way other experts can assess and critique
      (transparency). But the democratic context in need of weight-of-evidence analysis
      also places additional constraints on the process, including communicability of
      the process to the general public, the need for an approach that can be used
      across a broad range of contexts (scope), and timeliness of process
      (practicality). I will compare qualitative and quantitative approaches with
      respect to both traditional epistemic criteria and criteria that arise from the
      democratic context, and argue that a qualitative explanatory approach can best
      meet the criteria and elucidate how to utilize the other approaches. This should
      not be surprising, as the approach I argue for is the one that most closely
      tracks general scientific reasoning.

PMID- 23002583
TI  - Climate science, character, and the "hard-won" consensus.
AB  - What makes a consensus among scientists credible and convincing? This paper
      introduces the notion of a "hard-won" consensus and uses examples from recent
      debates over climate change science to show that this heuristic standard for
      evaluating the quality of a consensus is widely shared. The extent to which a
      consensus is "hard won" can be understood to depend on the personal qualities of
      the participating experts; the article demonstrates the continuing utility of the
      norms of modern science introduced by Robert K. Merton by showing that
      individuals on both sides of the climate science debate rely intuitively on
      Mertonian ideas--interpreted in terms of character--to frame their arguments.

PMID- 23002584
TI  - [Isotopic composition and isotope tracing of sulfur in atmospheric precipitation
      at the head area of the Three Gorges Reservoir, China].
AB  - Rainwater samples were collected in the head area of the Three Gorges Reservoir
      from June 2009 to July 2010. The SO4(2-) content and the characteristics of
      sulfur isotopic composition were determined. The results showed that the
      concentrations of SO4(2-) ranged from 31.4-668. 1 micromol x L(-1) with a
      weighted average of 161.9 micromol x L(-1), whereas the variation of delta34S
      values for SO4(2-) ranged from -2.14 per hundred to 6.07 per hundred with an
      annual average of 2.06 per hundred +/- 1.97 per hundred. Significant seasonal
      variations were found in the SO4(2-) content, which were higher in winter and
      spring and lower in summer and autumn. The delta34S values for SO4(2-) measured
      in winter were much higher than those in the other seasons. Analysis of the
      delta34S values showed that the biogenic sulfur might have significant
      contribution to the acidity of rainwater, especially in summer and autumn.

PMID- 23002585
TI  - [Characterization and reconstruction of aerosol light scattering coefficient at
      Chengdu during biomass burning and dust storm period in spring].
AB  - Aerosol samples for PM2.5 were collected from 19 April to 17 May in 2009 at
      Chengdu. The concentrations of organic carbon, element carbon, water-solubility
      ions, crustal elements and levoglucosan of all particle samples were determined
      by thermal/ optical carbon analyzer,ion chromatography, X-ray fluorescence
      spectrometer and high performance anion exchange chromatography, respectively. In
      situ scattering coefficients (b(sp)) and meteorological parameters for this
      period were also conducted. Ambient scattering coefficients were reconstructed by
      IMPROVE formula and compared with measured scattering coefficients. The results
      showed that the average mass concentration of PM2.5 and measured b(sp) were 133.2
      microg x m(-3) and 530 Mm(-1), respectively. Levoglucosan and crustal elements
      were good traces for biomass burning and dust storm events, respectively. The
      calculated b'sp was 504 Mm(-1) during campaigning period. The major contributors
      to scattering coefficients included: (NH4)2SO4 (26%), NH4NO3 (15%), OM (53%), FS
      (4%) and CM (2%), respectively. The calculated b'sp was 575 Mm(-1) and the
      dominant species were FS (17%) and CM (21%) during dust storm period (DS). The
      calculated b'sp was 635 Mm(-1) and OM contributed 62% during biomass burning (BB)
      period.

PMID- 23002586
TI  - [Aerosol optical thickness of the atmospheric aerosol over Taihu Lake and its
      features: results of in-site measurements].
AB  - Based on the data measured in situ by an automatic sun tracking photometer (CE
      318), the aerosol optical thickness (AOT) and the corresponding Angstrom
      coefficient alpha of the atmospheric aerosol over Taihu Lake from November 2005
      to October 2010 were collected. The results showed that high values of AOT over
      Taihu Lake were measured in summer (June to July) whereas low values were
      detected in autumn and winter (October to January). However, the low and high
      values of a appeared in spring (March to April) and in autumn (September to
      November), respectively. The variations of AOT and a over Taihu Lake may be
      related to weather patterns in this region. Based on the frequency distribution,
      AOT (500 nm) had only one peak value, with a maximum frequency of 0.4-0.6 and a
      yearly average value of 0.80, accounting for 26% of the total sample. Calculated
      from the mean AOT (500 nm), the solar radiation reduction was reduced by at least
      50% by the atmospheric aerosol, resulting in more turbid atmosphere in this
      region and consequently heavy fog and haze. There were two peak values of the
      Angstrom coefficient alpha, with the maximum frequency ranging from 1.1-1.3 and
      1.3-1.5 and a yearly average value of 1.17, accounting for 30% of the total
      sample. Significant variations were also observed in the daily average values of
      AOT (500 nm) and a, indicating the coexistence of different types of aerosols
      over Taihu Lake. The mean value of AOT (500 nm) declined when a increased. To sum
      up, values of AOT (500 nm) over Taihu Lake changed greatly with time, and the
      aerosol should be classified as an urban-industrial aerosol.

PMID- 23002587
TI  - [Seasonal variations in the vertical distribution of aerosols during dry haze
      periods in regions around Shanghai].
AB  - Based on the onboard lidar data from CALIPSO satellite of National Aeronautics
      and Space Administration (NASA) from January 2007 to November 2010, the vertical
      distribution of optical and micro-physical properties of aerosols around Shanghai
      during the haze periods when relative humidity less than 80% were revealed by
      analyzing the parameters of 532 nm total attenuated backscatter coefficient,
      volume depolarization ratio and total attenuated color ratio. The results showed
      that during dry haze periods, the scattering ability of lower troposphere (0-2
      km) was the highest and the main constituents were regular aerosols. The
      scattering ability of the upper troposphere (8-10 km) was the lowest and the
      proportion of irregular aerosols was the highest among the five altitude layers.
      In addition, the scattering ability of the altitude range (2-8 km) was lower than
      that of the lower troposphere, and the scattering ability and irregularity of
      aerosols at different altitude levels within the range were close to each other.
      Fine particle aerosols were the dominant aerosols in altitude range of 0-10 km.
      To be noted, the proportion of fine particles decreased with increasing altitude
      within the altitude range of 2-8 km. The proportion of large and irregular
      aerosols were higher in spring, whereas the proportion of fine and regular
      aerosols were higher in summer. According to the analysis of a dry haze episode
      on May 7th, 2007, it was found that a mass of aerosols mainly distributed within
      the altitude range of 0-1.5 km and partially within the altitude range of 4.0-5.5
      km. The HYSPLIT model was applied to analyze the sources of aerosols in the
      episode, and the results indicated that the dry haze was mainly caused not only
      by local emissions but also by the dust aerosols transported from Mongolia, the
      northwest and north of China by the airflow.

PMID- 23002589
TI  - [Seasonal distribution of water-soluble inorganic ions in the atmospheric aerosol
      in Qingdao].
AB  - To collect comprehensive information on the characteristics and sources of water
      soluble ions in the atmospheric aerosol in Qingdao, samples of total suspended
      particles (TSP) were collected from January to December 2008, and the
      concentrations of the major water-soluble inorganic ions were analyzed using ion
      chromatography. The results showed that SO4(2-), NO3-, NH4+ and Cl- were the
      dominant water-soluble ions in TSP, the sum of the four accounting for 86.9% of
      water-soluble ions in mass concentration. TSP and water-soluble inorganic ions
      showed obvious seasonal variations and there were a variety of sources. The mass
      concentrations of Na+, NH4+, Ca2+, F- and Mg2+ were highest in winter and lowest
      in summer. The concentrations of K+ and PO4(3-) were highest in autumn and lowest
      in summer. NO3-, Cl- and SO4(2-) concentrations had the highest values in spring,
      winter, and spring, respectively. Different weather conditions had great
      influence on the concentrations of TSP and water-soluble ions. The mass
      concentrations of TSP were highest in dust weather followed by haze, smog, fog
      and sunny days. The average mass concentrations of Na+ , Mg2+, Ca2+, F- , Cl- and
      PO4(3-) were highest in smog days while the other ions in haze days.

PMID- 23002588
TI  - [Size distributions and diurnal variations in the concentrations of polycyclic
      aromatic hydrocarbons in winter in urban and suburban Nanjing, China].
AB  - The contamination status and distribution characteristics of particulate
      polycyclic aromatic hydrocarbons (PAHs) were investigated in aerosols of urban
      and suburban Nanjing. A total of 17 PAHs were analyzed in the aerosol samples
      collected in daytime and nighttime during January 1st to 10th, 2010 in Nanjing
      University (NU) and Nanjing University of Information Science & Technology
      (NUIST). The PAH concentrations at the urban and suburban sites were 41.36-220.35
      ng x m(-3) and 45.10-200.86 ng x m(-3), respectively, of which about 66%-67% was
      absorbed by fine particles (Dp < or = 2.1 microm). High levels of particulate
      PAHs were detected at both sampling sites with different diurnal variations. The
      higher total-PAH concentration occurred in the daytime at the urban site and in
      the nighttime at the suburban site. The change of prevailing wind direction and
      high-pressure weather system had significant impact on the variation of PAH
      concentrations, which were dominated by fine and coarse particles in urban and
      suburban regions, respectively. Difference in PAH size distributions was found
      for low weight molecular PAHs (LWM-PAH) and high weight molecular PAHs (HWM-PAH)
      in urban and suburban areas. The concentrations of 2-3 ring PAHs were higher at
      the suburban site than those at the urban site, whereas larger amounts of 4-6
      ring PAHs were found at the urban site than at the suburban site. The
      concentration peaks in coarse particle size of high-molecular-weight PAHs found
      in our study were larger than those in some of the previous studies, which might
      be due to the high carbon content in coarse particles in the atmosphere at our
      sites. Analysis of diagnostic ratios indicated that the PAHs particles at both
      two sites have the same sources, including combustion of coal and biomass,
      vehicular exhaust and suburban industrial emission.

PMID- 23002590
TI  - [Pollution characteristics of microbial aerosols generated from a municipal
      sewage treatment plant].
AB  - To characterize the pollution characteristics of microbial aerosols emitted from
      municipal sewage treatment plants, microbial aerosols were sampled with an
      Andersen 6-stage impactor at different treatment units of a Xi'an sewage
      treatment plant between June 2011 and July 2011. The plate-culture and colony
      counting methods were employed to determine the concentrations, particle size
      distributions and median diameters of the airborne bacteria, fungi and
      actinomycetes. The results showed that the highest concentrations of bacteria (7
      866 CFU x m(-3) +/- 960 CFU x m(-3)) and actinomycetes (2 139 CFU x m(-3) +/- 227
      CFU x m(-3)) were found in the sludge-dewatering house while the highest fungi
      concentration (2156 CFU x m(-3) +/- 119 CFU x m(-3)) in the oxidation ditch. The
      airborne bacteria, fungi and actinomycetes all showed a skewed distribution in
      particle size. The peaks of bacteria and fungi were in the size range of 2.1-3.3
      microm, whereas the peak of airborne actinomycetes was between 1. 1-2.1 microm in
      size. In general, the order of the median diameters of different microbial
      aerosols generated from the sewage treatment plant was airborne bacteria >
      airborne fungi > airborne actinomycetes. In addition, the spatial variation
      characteristics of microbial aerosols showed that the larger the particle size of
      the microorganism, the faster the reducing rate of the aerosol concentration. The
      variations in the reducing rate of concentration with particle sizes can be
      ordered as airborne bacteria > airborne fungi > airborne actinomycetes.

PMID- 23002591
TI  - [Estimation of the effect derived from wind erosion of soil and dust emission in
      Tianjin suburbs on the central district based on WEPS model].
AB  - Due to the lack of a prediction model for current wind erosion in China and the
      slow development for such models, this study aims to predict the wind erosion of
      soil and the dust emission and develop a prediction model for wind erosion in
      Tianjin by investigating the structure, parameter systems and the relationships
      among the parameter systems of the prediction models for wind erosion in typical
      areas, using the U.S. wind erosion prediction system (WEPS) as reference. Based
      on the remote sensing technique and the test data, a parameter system was
      established for the prediction model of wind erosion and dust emission, and a
      model was developed that was suitable for the prediction of wind erosion and dust
      emission in Tianjin. Tianjin was divided into 11 080 blocks with a resolution of
      1 x 1 km2, among which 7 778 dust emitting blocks were selected. The parameters
      of the blocks were localized, including longitude, latitude, elevation and
      direction, etc.. The database files of blocks were localized, including wind
      file, climate file, soil file and management file. The weps. run file was edited.
      Based on Microsoft Visualstudio 2008, secondary development was done using C + +
      language, and the dust fluxes of 7 778 blocks were estimated, including creep and
      saltation fluxes, suspension fluxes and PM10 fluxes. Based on the parameters of
      wind tunnel experiments in Inner Mongolia, the soil measurement data and climate
      data in suburbs of Tianjin, the wind erosion module, wind erosion fluxes, dust
      emission release modulus and dust release fluxes were calculated for the four
      seasons and the whole year in suburbs of Tianjin. In 2009, the total creep and
      saltation fluxes, suspension fluxes and PM10 fluxes in the suburbs of Tianjin
      were 2.54 x 10(6) t, 1.25 x 10(7) t and 9.04 x 10(5) t, respectively, among
      which, the parts pointing to the central district were 5.61 x 10(5) t, 2.89 x
      10(6) t and 2.03 x 10(5) t, respectively.

PMID- 23002592
TI  - [Variation of nutrient concentrations at the inshore coastal area of northern
      Jiangsu province and the occurrence of green tide caused by Enteromorpha
      prolifera].
AB  - Based on the investigation of the inshore coastal area of northern Jiangsu
      province with occurrence of green tide caused by Enteromorpha prolifera, which
      was performed in five voyages during March to June 2010, the variation of
      nutrient concentrations and its distribution characteristics were studied in this
      paper. The results showed that the concentrations of nutrients were relatively
      high in this region due to the terrestrial runoff and northern Jiangsu coastal
      current, which contributed to the outbreak of green tide. The highest
      concentrations of dissolved inorganic N (DIN), PO4(3-)-P and SiO3(2-)-Si were
      23.04, 0. 55 and 15.85 micromol x L(-1), respectively. In spring, due to the
      strong life activities of plankton and the intake of nutrients by green tide, the
      concentrations of NO(3-)-N, PO4(3-)-P, SiO3(2-)-Si and DIN all showed a tendency
      of decreasing from the first to the fifth voyage. Besides, the closer the N/P
      ratios in water and in the body of plankton, the faster the plankton grows. The
      N/P ratios measured in the fourth and fifth voyages were relatively favorable for
      the growth of Enteromorpha prolifera. The distribution characteristics of
      nutrients had a tendency of decreasing from inshore to offshore in all voyages.

PMID- 23002593
TI  - [Analysis on characteristics of red tide in Fujian coastal waters during the last
      10 years].
AB  - There were 161 red tide events collected during the last 10 years from 2001 to
      2010 in Fujian coastal waters. Comprehensive analysis was performed using
      statistical methods and the results indicated the following characteristics of
      the temporal and spatial distribution of red tide in Fujian coastal waters: (1)
      Outbreaks of red tide often occurred between April and September, and the peak
      period was in May and June. Most red tide events lasted for 2 to 4 days, and the
      affected area was below 50 square kilometers. The first outbreak of red tide
      tended to occur earlier in recent years, and the lasting time became longer. (2)
      There were 20 species of organisms causing the red tides in Fujian coastal
      waters, among which 10 species were Bacillariophyta, 9 species were Dinophyta and
      1 species was Protozoa. Prorocentrum donghaiense was the most frequent cause of
      red tides, followed by Noctiluca scintillans, Skeletonema costatum and
      Chaetoceros sp.. The species caused red tides obeyed the succession law and there
      were always new species involved. (2) In terms of spatial distribution, outbreaks
      of red tides mainly occurred in the coastal waters of Ningde, Fuzhou and Xiamen.
      The species causing red tides were Prorocentrum donghaiense and Noctiluca in the
      coastal waters in the north of Pingtan, Fujian Province, Skeletonema costatum and
      Chaetoceros in the coastal waters in the south of Pingtan, Fujian Province. The
      comprehensive analysis of the characteristics of red tides during the last 10
      years is expected to provide scientific and reasonable basis for the prevention,
      reduction and forecast of red tides in Fujian coastal waters.

PMID- 23002594
TI  - [Review on HSPF model for simulation of hydrology and water quality processes].
AB  - Hydrological Simulation Program-FORTRAN (HSPF), written in FORTRAN, is one ol the
      best semi-distributed hydrology and water quality models, which was first
      developed based on the Stanford Watershed Model. Many studies on HSPF model
      application were conducted. It can represent the contributions of sediment,
      nutrients, pesticides, conservatives and fecal coliforms from agricultural areas,
      continuously simulate water quantity and quality processes, as well as the
      effects of climate change and land use change on water quantity and quality. HSPF
      consists of three basic application components: PERLND (Pervious Land Segment)
      IMPLND (Impervious Land Segment), and RCHRES (free-flowing reach or mixed
      reservoirs). In general, HSPF has extensive application in the modeling of
      hydrology or water quality processes and the analysis of climate change and land
      use change. However, it has limited use in China. The main problems with HSPF
      include: (1) some algorithms and procedures still need to revise, (2) due to the
      high standard for input data, the accuracy of the model is limited by spatial and
      attribute data, (3) the model is only applicable for the simulation of well-mixed
      rivers, reservoirs and one-dimensional water bodies, it must be integrated with
      other models to solve more complex problems. At present, studies on HSPF model
      development are still undergoing, such as revision of model platform, extension
      of model function, method development for model calibration, and analysis of
      parameter sensitivity. With the accumulation of basic data and imorovement of
      data sharing, the HSPF model will be applied more extensively in China.

PMID- 23002595
TI  - [Parameter uncertainty analysis for urban rainfall runoff modelling].
AB  - An urban watershed in Xiamen was selected to perform the parameter uncertainty
      analysis for urban stormwater runoff modeling in terms of identification and
      sensitivity analysis based on storm water management model (SWMM) using Monte
      Carlo sampling and regionalized sensitivity analysis (RSA) algorithm. Results
      show that Dstore-Imperv, Dstore-Perv and Curve Number (CN) are the identifiable
      parameters with larger K-S values in hydrological and hydraulic module, and the
      rank of K-S values in hydrological and hydraulic module is Dstore-Imperv > CN >
      Dstore-Perv > N-Perv > conductivity > Con-Mann > N-Imperv. With regards to water
      quality module, the parameters in exponent washoff model including Coefficient
      and Exponent and the Max. Buildup parameter of saturation buildup model in three
      land cover types are the identifiable parameters with the larger K-S values. In
      comparison, the K-S value of rate constant in three landuse/cover types is
      smaller than that of Max. Buildup, Coefficient and Exponent.

PMID- 23002596
TI  - [Estimation of DOC concentrations using CDOM absorption coefficients: a case
      study in Taihu Lake].
AB  - Dissolved organic carbon (DOC) is the largest organic carbon stock in water
      ecosystems, which plays an important role in the carbon cycle in water.
      Chromophoric dissolved organic matter (CDOM), an important water color variation,
      is the colored fraction of DOC and its absorption controls the instruction of
      light under water. The available linkage between DOC concentration and CDOM
      absorptions enables the determination of DOC accumulations using remote sensing
      reflectance or radiance in lake waters. The present study explored the multi
      liner relationship between CDOM absorptions [a(g) (250) and a(g) (365)] and DOC
      concentrations in Taihu Lake, based on the available data in 4 cruises (201005,
      201101, 201103, 201105) (totally 183 sampling sites). Meanwhile, the results were
      validated with the data of the experiment carried out from August 29 to September
      2, 2011 in Taihu Lake (n = 27). Furthermore, a universal pattern of modeling from
      remote sensing was built for lake waters. The results demonstrated that this
      method provided more satisfying estimation of DOC concentrations in Taihu Lake.
      Except the data obtained in January 2011, the fitted results of which were not
      conductive to the winter dataset (201101) in Taihu Lake, due to the diverse
      sources and sinks of DOC and CDOM, the multi-liner relationship was robust for
      the data collected in the other three cruises (R2 = 0.64, RMSE = 14.31%, n =
      164), which was validated using the 201108 sampling dataset (R2 = 0.67, RMSE =
      10.58%, n = 27). In addition, the form of the statistic model is universal, to
      some extent, for other water areas, however, there is difference in the modeling
      coefficients. Further research should be focused on the parameterization using
      local data from different lakes, which provides effective methodology for the
      estimation of DOC concentrations in lakes and other water regions.

PMID- 23002597
TI  - [Weight parameters of water quality impact and risk grade determination of water
      environmental sensitive spots in Jiashan].
AB  - For the safety of the water environment in Jiashan county in Zhejiang Province,
      one-dimensional hydrodynamic and water quality models are established based on
      three large-scale monitoring of hydrology and water quality in Jiashan county,
      three water environmental sensitive spots including Hongqitang dam Chijia
      hydrological station and Luxie pond are selected to investigate weight parameters
      of water quality impact and risk grade determination. Results indicate as follows
      (1) Internal pollution impact in Jiashan areas was greater than the external, the
      average weight parameters of internal chemical oxygen demand (COD) pollution is
      55.3%, internal ammonia nitrogen (NH(4+)-N) is 67.4%, internal total phosphor
      (TP) is 63.1%. Non-point pollution impact in Jiashan areas was greater than point
      pollution impact, the average weight parameters of non-point COD pollutions is
      53.7%, non-point NH(4+)-N is 65.9%, non-point TP is 57.8%. (2) The risk of
      Hongqitang dam and Chijia hydrological station are in the middle risk. The risk
      of Luxie pond is also in the middle risk in August, and in April and December the
      risk of Luxie pond is low. The strategic decision will be suggested to guarantee
      water environment security and social and economic security in the study.

PMID- 23002598
TI  - [Diurnal variation and evaluation of water quality in different seasons of Panxi
      River in Chongqing].
AB  - Based on the investigation of water quality of Panxi River in different seasons,
      2010, we assessed the diurnal variation of water quality in different seasons and
      the characteristics of water quality changes within a day by using non-parametric
      test, analysis of variance and grey relationship analysis. The results showed
      that the differences were not significant for Zn and Cu (P > 0.05), but
      significant differences existed among the pH, EC, DO, COD, TP, TSS, BOD5, NO(3-)
      N, TN, NH(4+)-N, Pb and Cd contents. It showed that the minimum DO concentration
      occurred in winter, and the maximum of BOD5, COD and TOC concentrations occurred
      in winter, and the maximum NO(3-)-N concentration occurred in summer and the
      minimum TN, NH(4+)-N and TP concentrations occurred in summer. The diurnal
      variation of dissolved heavy metals showed relatively larger fluctuations in
      different seasons. The diurnal variation of different water quality parameters
      presented distinct patterns: diurnal variation of organic pollutants and
      nutrients showed the peak at 12:00 to 16:00 and dissolved heavy metals peaked at
      12:00. The results of grey relationship analysis for surface water indicated that
      the water quality in spring was in the II class at 06:00 and 08:00 and was
      inferior to theV class for the rest hours; and the water quality in summer was in
      the II class; and the water quality in autumn was inferior to the V class at
      06:00 and 16:00 and was in the II class for the rest hours; and the water quality
      in winter was in the II class at 08:00 and was inferior to the V class for the
      rest hours.

PMID- 23002599
TI  - [Responses of wetland water quality to influence the strengthness of urbanization
      in Nanjing, China].
AB  - 28 typical wetlands were selected to monitor the contaminants in water monthly,
      that influenced by urbanization in different scales. On the other hand, the land
      use types such as impervious area and forest area in the catchments of urban
      wetlands were analyzed by GIS and landscape ecology. And then the effects of
      urbanization index (UEI) was employed to reveal the relationship between
      urbanization level and water quality in Xianlin New City of Nanjing. Results
      indicated that: (1) the seasonal variations of water quality showed that water
      quality in summer was worse than those in other seasons, and the water quality in
      winter was good. However there were no significant differences between the spring
      and the autumn. (2) the relationship was significant between urbanization level
      and water quality, and the water quality tended to be getting worse when the
      urbanization level was getting higher. The concentrations of TP, TN, NH(4+)-N,
      and Chla were 0.27, 1.07, 0.15 and 17.94 mg x L(-1) respectively in the high
      urbanization (HU) level wetland while the concentrations were 0.12, 0.56, 0.12
      and 4.85 mg x L(-1) in the low urbanization (LW) level wetland. (3) there was a
      threshold between UEI and the water quality. On the whole, the water quality
      would get worse quickly when the value of UEI exceeded 2.2.

PMID- 23002600
TI  - [Studies on relationship of phytoplankton and water environmental factors in
      Shahu Lake].
AB  - Analysis approaches of correlation, multiple stepwise regression and canonical
      correspondence analysis were employed between phytoplankton and water
      environmental factors in ShaHu Lake based on the data from Apr. 2009 to Jan.
      2010. The results showed that the correlation between phytoplankton density,
      phytoplankton biomass, chlorophyll-a and water temperature (WT), total nitrogen
      (TN), total phosphorus (TP), potassium permanganate index,5 days biochemical
      oxygen demand (BOD5) was positive, and phytoplankton density, phytoplankton
      biomass, chlorophyll-a and Secchi-depth (SD) was negatively correlated. Followed
      by the importance of environmental factors which affected phytoplankton density
      in Shahu Lake ranged as follows: WT, potassium permanganate index, SD, BOD5, TP,
      TN. Those affected phytoplankton biomass ranged as follows: WT,TP, potassium
      permanganate index,SD,TN. Those affected on chlorophyll-a ranged as follows:
      potassium permanganate index, WT, SD, TP, TN, BOD5. CCA result showed that 16
      species of phytoplankton were divided into 3 groups which had the obvious
      seasonal distribution characteristics in Shahu Lake. SD, potassium permanganate
      index,WT, TN, TP were the main water environmental factors correlated with the
      distribution of phytoplankton community of Shahu Lake.

PMID- 23002601
TI  - [Influence on the spatial distribution of fish in Taizi River basin by
      environmental factors at multiple scales].
AB  - The deterioration of fish is influenced by various types of environmental
      factors. To develop protection plans that are more suitable, non-metric
      multidimensional scaling analysis (NMS) was used to investigate the influence of
      environmental factors at multiple scales on the spatial distribution of fish. The
      results of cluster analysis showed that there were three types of spatial
      distribution of fish, i.e. upstream timber and tributary headstream area,
      midstream hilly area, and downstream plain area. Results of NMS analysis
      indicated the significant correlations between spatial distribution of fish and
      environmental factors at multiple scales. Altitude, stream order and land use
      were three important factors influencing the fish distribution at the watershed
      scale. Combination of velocity and depth, habitat inhomogeneity and electrical
      conductivity significantly affected fish distribution at the reach scale, whereas
      the quality of bottom material showed significant influence at the microhabitat
      scale. Therefore, the effect of specific environmental factors at multiple scales
      should be taken into consideration in the basin fish conversation management.

PMID- 23002602
TI  - [Comparison and application of biological indices of macroinvertebrates in river
      health assessment].
AB  - The different biological indices usually result in different results in the river
      health assessment. It is imperative and valuable to identify the correlation
      among different indices and their applicability for assessing stream health. In
      this study, totally five biological indices were selected and compared in the
      investigation of macroinvertebrate communities in the Taizi river. The results
      showed significant correlations among the five indices. However, due to the
      difference in health rating criteria for each biological index, different results
      of health ratings were obtained when different indices were used. The responding
      sensitivities to disturbance caused by different types of human activities were
      studied for each index to determine their applicability in assessment of river
      health. The data indicated that the BI index had significant correlations with
      land use and dissolved oxygen and was a good indicator for these two types of
      disturbance. The FBI index could well reflect the acid and ammonia contamination
      of the investigated stream. Strong negative correlation was found between the
      ASPT index and several water quality parameters concerning oxygen consumption.
      The B-IBI index had a significant negative correlation with the total nitrogen
      concentration, being a good indicator for nitrogen contamination. Besides, the B
      IBI index was also significantly correlated to disturbance caused by other types
      of human activities and can be used as an indicator for both land use and aquatic
      pollution. To be concluded, the BI index and ASPT index can be individually used
      to assess the land use of a riverine and the impact of hydrochemical index on the
      ecosystems, whereas the B-IBI index could be a suitable indicator for evaluating
      the stream health correlated with various human activities.

PMID- 23002603
TI  - [Spatial and temporal distribution of total mercury (T-Hg) in different water
      bodies of Nam Co, Tibetan Plateau].
AB  - To investigate the tempo-spatial distribution of total mercury (T-Hg)
      concentration in water bodies in the Nam Co basin on the Tibetan Plateau,
      inflowing river water and surface lake water samples were collected from 2007 to
      2010. The T-Hg concentration and its relationship with precipitation and river
      runoff were analyzed. The results showed that the average T-Hg concentration was
      (1.09 +/- 0.73) ng x L(-1) and (2.87 +/- 2.59) ng x L(-1) for surface lake water
      and river water, respectively, both of which were significantly lower than those
      of Hg contaminated waters. T-Hg concentration in off-shore lake water was much
      higher during the monsoon season than in the non-monsoon season, and its level
      and spatial variation were significantly greater than those in central lake
      water. T-Hg concentration in river water showed significant seasonal variations
      with the highest values during the monsoon season and the lowest during the post
      monsoon season, which were in accordance with the variations of precipitation. A
      fixed point observation at Niyaqu River indicated that the temporal changes of
      the T-Hg concentrations in river water were in accordance with those of the
      runoff. The spatial distribution features of T-Hg concentrations in inflowing
      river water varied in different periods, possibly resulting from the differences
      in drainage areas, background mercury levels in soils, and water supplies for
      rivers at different locations of the Nam Co basin.

PMID- 23002604
TI  - [Temporal and spatial variations of major ions in Nam Co Lake water, Tibetan
      Plateau].
AB  - In order to investigate the temporal and spatial variations, sources, and major
      controlling factors of the major ions in Nam Co Lake water, inshore surface water
      samples were collected at a fixed site (30 degrees 47.27'N, 90 degrees 58.53'E,
      4718 m a. s. l.) from 2006 to 2010, at the vertical profiles in the center of the
      lake in August 2009, and at both the vertical profiles in the center of the lake
      and at the surface layers of different sites in the Nam Co Lake in October 2010.
      The results indicated that Na+ was the dominant cation and HCO3- was the dominant
      anion in the lake water. The concentrations of most ions were higher in monsoon
      seasons (June - September) and lower in non-monsoon seasons, especially when the
      lake was frozen (January -April). However, the Ca2+ concentration showed a
      reverse trend of seasonal variations, namely, higher values in the frozen period
      and lower in monsoon seasons. Analysis of water samples collected from the
      vertical profiles indicated that the concentrations of all ions except Ca2+
      increased with the depth in nonmonsoon seasons (e. g. October). The major ions in
      Nam Co Lake were mainly contributed by river input. There were a variety of
      factors that influenced the temporal and spatial variations of the major ions in
      the Nam Co Lake, such as evaporation, precipitation, pH values, etc., among
      which, evaporation was the most important controlling factor, causing the
      increasing Na+ concentration and decreasing Ca2+ concentration in the lake water.

PMID- 23002605
TI  - [Eutrophication control in local area by physic-ecological engineering].
AB  - An integrated physical and ecological engineering experiment for ecological
      remediation was performed at the Maixi River bay in Baihua Reservoir Guizhou
      Province, China. The results show that eutrophic parameters, such as total
      nitrogen, total phosphorus, chlorophyll a and chemical oxygen demand from the
      experimental site (enclosed water) were significantly lower than those of the
      reference site. The largest differences between the sites were 0.61 mg x L(-1),
      0.041 mg x L(-1), 23.06 microg x L(-1), 8.4 mg x L(-1) respectively; experimental
      site transparency was > 1.50 m which was significantly higher than that of the
      reference site. The eutrophic index of the experimental site was oligo-trophic
      and mid-trophic, while the control site was mid-trophic state and eutrophic
      state. Phytoplankton abundance was 2 125.5 x 10(4) cells x L(-1) in June, 2011 at
      the control site,but phytoplankton abundance was lower at the experimental site
      with 33 x 10(4) cells x L(-1). Cyanobacteria dominated phytoplankton biomass at
      both sites, however the experimental site consisted of a higher proportion of
      diatoms and dinoflagellates. After more than one year of operation, the
      ecological engineering technology effectively controlled the occurrence of algae
      blooms, changed phytoplankton community structure, and controlled the negative
      impacts of eutrophication. Integrating physical and ecological engineering
      technology could improve water quality for reservoirs on the Guizhou plateau.

PMID- 23002606
TI  - [Nitrogenous fluxes and its self-purification capacity in Lake Taihu].
AB  - The various forms of nitrogen in 25 rivers surrounding Lake Taihu as well as in
      some typical lake zones such as Meiliang Bay and East Lake Taihu were analyzed
      during the hydrological year of 2009-2010. Furthermore, the nitrogenous self
      purification capacity of Lake Taihu was studied in combined with the
      investigation of water flow, cyanobacteria salvages and aquatic product outputs.
      In the whole hydrological year, the inflow and outflow fluxes of total nitrogen
      (TN) were 7.00 x 10(4) t and 4.01 x 10(4) t, respectively. About 3.02 x 10(4) t
      and 0.20 x 10(4) t nitrogen in water body were removed by denitrification and
      sediment adsorption during this hydrological year, respectively, suggesting a
      strong nitrogen self-purification capacity of Lake Taihu. The potential
      denitrification is stronger in western Lake Taihu (e.g., Meiliang Bay) than that
      in eastern Lake Taihu (e.g., East Lake Taihu), and is stronger in summer than
      that in other seasons. Thus, the nitrogenous self-purification capacity plays an
      important role in nitrogenous transference and transformation in Lake Taihu.

PMID- 23002608
TI  - [Spatial distribution character of phosphorus fractions in surface sediment from
      Chaohu Lake].
AB  - Phosphorus fractions, organic matter and particle size of the surface sediment
      from Chaohu Lake were analyzed for spatial distribution and the risk of
      phosphorus release. The result showed that total phosphorus (TP) of surface
      sediment was 790 mg x kg(-1), which was 55% higher than that in 1980s, with 386
      mg x kg(-1) higher in western lake and 211 mg x kg(-1) higher in eastern lake.
      NaOH-Pi of sediment ranged from 55 to 648 mg x kg(-1), and occupied average 25%
      of TP. NaOH-Po of sediment ranged from 27 to 468 mg x kg(-1), and occupied
      average 17% of TP. NaOH-Pi and NaOH-Po in western lake were 331 mg x kg(-1) and
      225 mg x kg(-1), which were significantly higher than those in eastern lake. Ca-P
      and Res-P accounted for 18% and 40% of TP, and were equably distributed in the
      lake. TP, NaOH-Pi and NaOH-Po of sediment in the western lake increased
      intensively with the depth, while Ca-P and Res-P showed no significant change in
      the vertical profile in the lake. Profile of phosphorus fractions showed that
      NaOH-Pi and NaOH-Po were the dominant factions of the increasing phosphorus
      sedimentation in the western lake. Phosphorus of sediment in the western lake
      will release more easily to the water with higher organic matter and higher
      content of sandy silt.

PMID- 23002607
TI  - [Response of phosphorus components in sediments from eutrophic lake to external
      sulfate].
AB  - A six week experiment under indoor simulated condition was carried out to
      investigate the external sulfate transformation between the sediments and
      overlying water from Lake Nanhu in Wuhan, China, and the influence of sulfate on
      the phosphorus components was also studied. The results showed that the sulfate
      input increased the pH and lowered the Eh in the overlying water. The sulfate
      concentration in the overlying water decreased with time, and it was assumed that
      there existed an obvious transformation of sulfate to other forms of sulfur
      compounds according to the variation of sulfate concentration in the pore water.
      The sulfate reduction index increased with higher input content of sulfate. The
      amount of sulfate reducing bacteria (SRB) in the sediments achieved the peak
      value in the second week, and the SRB amounts of S500 and S1000 were much higher
      than that of the control. 31P-NMR was used to characterize the relative quantity
      of phosphorus compounds in the sediment extracts leached by NaOH-EDTA. The
      components of phosphorus in Nanhu Lake sediment were mainly orthophosphate,
      phosphate monoester, phosphodiester and pyrophosphate. The predominant one was
      orthophosphate (84.10%-95.54% of total phosphorus). The contents of other
      phosphorus components were followed: phosphate monoester > phosphodiester >
      pyrophosphate, and they increased due to the input of sulfate during the first
      four weeks, and decreased in the last two weeks. The external sulfate accelerated
      the release of orthophosphate from sediments to overlying water in a whole, and
      increased the contents of phosphate monoester, phosphodiester and pyrophosphate
      in sediments when the amounts of sulfate reducing bacteria were high.

PMID- 23002609
TI  - [Long-range transport potential of typical organic pollutants in Nanjing].
AB  - In this study, the long-range transport potentials (LRTP) of typical organic
      pollutants including p,p'-DDT, gamma-HCH, BaP and HCB in air and water of Nanjing
      were estimated using the TaPL3 model. The research results showed that the
      characteristic travel distances (CTD) of BaP and p,p'-DDT through air were
      relatively low, 198 km and 255 km, respectively, indicating relatively low LRTP
      and difficulty in pollution dispersion. In contrast, gamma-HCH and HCB tended to
      transport over longer distances through water and air, with CTD values of 91 558
      km and 19 056 km in water and 1 858 km and 21 104 km in air, respectively,
      indicating that the dispersion of pollution in air and water of the studied area
      was relatively easy. Furthermore, the stickiness of gamma-HCH and HCB in water
      was negative, and the values were -2.1 and -54.86, respectively, indicating that
      gamma-HCH and HCB tended to remain in the atmosphere. The mass fractions in air
      after they passed air and achieved the steady state were 0.551% and 2.2%,
      respectively, whereas the mass fractions in air after they passed water and
      achieved the steady state were 0. 149% and 1.05% , respectively, which were
      higher than those of p,p'-DDT and BaP.

PMID- 23002610
TI  - [Distribution of black carbon in the surface sediments of the East China Sea and
      their correlations with persistent organic pollutants].
AB  - Concentrations of black carbon (BC) were determined in the surface sediments from
      the inner continental shelf of the East China Sea (ECS). For comparison, the
      total organic carbon (TOC) contents, grain size distribution, concentrations of
      PAHs and DDTs in the sediments were also measured. Total concentration of BC
      ranged from 0.21 mg x g(-1) to 0.88 mg x g(-1), with the highest level in the
      depositional center of Yangtze-derived fine particles. Correlation was found to
      be insignificant between BC and TOC in the surface sediments, suggesting that
      they possibly came from different sources. The sediment particles showed
      significant spatial variations, whereas no significant spatial difference was
      found in BC content, indicating that the deposition process of BC was not
      controlled by particle size separation. In addition, a poor correlation between
      BC and PAHs or DDTs was reported in the estuarine-coastal sediments, probably due
      to the complicated hydrodynamic process and the heterogeneous sources of PAHs and
      DDTs.

PMID- 23002611
TI  - [Contamination characteristics of polycyclic aromatic hydrocarbons (PAHs) in
      surface water from Jialing River in Chongqing].
AB  - To understand the composition, sources and contamination characteristics of PAHs
      in surface water from Jialing River in Chongqing, water samples were collected
      from 8 different sections in August 2009 and the concentrations of the 16
      priority PAHs were determined using GC-MS. The results indicated that the
      concentration of Sigma PAHs (the total PAHs) in the water body ranged from 467.13
      to 987.97 ng x L(-1), with an average concentration of 702.91 ng x L(-1). PAHs
      concentrations in surface waters were positively correlated with the dissolved
      organic carbon content. The predominant PAHs in the water body were 2-3 ring
      PAHs, accounting for 68.90% of Sigma PAHs. The ratios of specific PAHs revealed
      that the main PAHs source in Cuntan was the combustion of wood and coal, the
      origin of PAHs in Caotianmen was mostly petrogenic; whereas the main PAHs source
      in other sampling sections of Jialing River in Chongqing was petroleum
      combustion. Compared with other areas in China, the PAHs contamination in Jialing
      River around Chongqing was at a relatively low level, however, the concentrations
      of BaP in the surface water of 5 sampling sites exceeded the environmental
      quality standards for surface water in China.

PMID- 23002612
TI  - [Levels, distribution and possible sources of polychlorinated biphenyls in river
      sediments from an electronic waste recycling area].
AB  - The concentrations of 144 polychlorinated biphenyls (PCBs) in the river sediments
      from Luqiao were analyzed by GC-muECD. The objectives of this study were to
      understand the contents, spatial distribution and possible sources of PCBs. The
      Sigma PCBs concentrations detected in the river sediments were in the range of
      1.66 to 5 930 ng x g(-1), with a mean of 763 ng x g(-1). Tri-CBs, tetra-CBs and
      penta-CBs were the primary PCB congeners in all samples, accounting for 2.63%
      57.6%, 10.4%-54.6% and 7.82%-46.1%, respectively. Octa-CBs and deca-CBs were the
      minor PCB congeners in all samples, with the percentages of 0-8.57% and 0-11.0%,
      respectively. The hierarchical cluster analysis (HCA) showed that 22 samples were
      mainly polluted by Ar1248, 9 samples were polluted by Ar1254, and 6 samples were
      contaminated by Ar1016, Ar1232 and Ar1242. The PCBs concentrations found in the
      present study were at an upper-middle level compared with those in other studies
      in the world. The PCBs pollution in the present area had a high ecological risk.

PMID- 23002613
TI  - [Assessment model for heavy metal pollution in sediment based on trapezoidal
      fuzzy numbers and case study].
AB  - Due to the practical shortcomings of the classical deterministic pollution
      assessment model, the theory of trapezoidal fuzzy numbers was introduced to the
      environmental assessment system. A fuzzy risk assessment model was built based on
      the geoaccumulation index and biotoxicity coefficients of heavy metals. Using the
      fuzzy pollution risk assessment model, the risk of heavy metal pollution was
      evaluated for the surface sediment of Dongting Lake. The results showed that the
      pollution risk in a descending order was Hg > Cd > Pb > Cu > Cr > Zn > As, with
      Hg,Cd and Pb being the priority pollutants in Dongting Lake. Both the intervals
      of possible values for the geoaccumulation indexes of heavy metals and their
      credible levels were calculated using this model. Compared with the results of
      the deterministic assessment model, the fuzzy pollution risk assessment model
      gave a better characetriztaion of the actual pollution status and spatial
      distribution difference of the heavy metals in the sediment of the studied region
      which is more objective and comprehensive.

PMID- 23002614
TI  - [Impact of coastal exploitation on the heavy metal contents in the sediment of
      Bohai Bay].
AB  - To explore the trend of the changes in ecological environment caused by
      reclamation and the situation of heavy metal pollution in Bohai Bay, the contents
      and spatial distribution of Cd, Pb, Cu and Zn in the surface sediments of Bohai
      Bay were collected in 2003 and 2011 and studied. The BCR three-stage sequential
      extraction procedure was applied to investigate the speciation and contents of
      four heavy metals (Cd, Pb, Cu and Zn) in the surface sediments of Bohai Bay in
      2011. The bioavailability of these four heavy metals was also determined
      preliminarily. Besides, the pollution level and potential ecological risk of
      these elements were evaluated using the potential ecological risk index and
      sediment enrichment factors. The results indicated that the contents of Cu, Cd
      and Pb in the surface sediments of Bohai Bay in 2011 were higher than those in
      2003, indicating an increased level of heavy metal pollution. The distribution of
      Cu, Zn and Cd showed essentially the same pattern, all with higher content in the
      central area of Bohai Bay. High content of Pb was found in the estuarine, the
      central and southern area of Bohai Bay. There were significant positive
      correlations among these four elements. The results indicated that these four
      elements probably had the same pollution source. Cu, Zn and Cd were mainly found
      in the residual fractions, whereas Pb was mainly found in the reducible
      fractions. The bioavailability of these four metals is listed here in descending
      order: Cd > Pb > Cu > Zn. The comprehensive assessment results showed that Cd was
      the primary element with high ecological risk while Cu, Zn, Pb were the minor
      ones with relatively low risk.

PMID- 23002615
TI  - [Spatial distribution and contamination evaluation of heavy metals in the
      intertidal surface sediments of Eastern Chongming].
AB  - Using the ArcGIS geostatistical analysis module, this work investigated the
      spatial distribution pattern of heavy metals (Cu, Pb, Zn, Cr, Cd) and their
      deposition fluxes in the intertidal surface sediments of Eastern Chongming based
      on the analysis of grain size, heavy metal concentrations and organic carbon
      content. The spatial interpolation (Kriging) was performed to estimate the
      deposition fluxes, and the contamination status of heavy metals was evaluated
      using geoaccumulation index and potential ecological risk index. The results
      showed that the average contents of Cu, Pb, Zn, Cr and Cd were 42, 27, 69, 71 and
      0.23 microg x g(-1), respectively, all of which exceeded the background value in
      the Shanghai tidal flat. The contents of heavy metals showed a landward as well
      as northward increasing trend due to the influences of sediment grain size and
      organic carbon content. The annual deposition of Cu, Pb, Zn, Cr and Cd in Eastern
      Chongming were 187, 121, 395, 312 and 1.04 t, respectively; the total deposition
      flux of these heavy metals was 11 g x (m2 x a)-1. Although the overall
      contamination level of heavy metals in Eastern Chongming was relatively low, Cd,
      Pb and Cu had a potential pollution threat to the sediment environment.

PMID- 23002616
TI  - [Speciation and vertical distribution of heavy metals in sediments of Baiyangdian
      Lake].
AB  - In order to find out the heavy metal concentrations and their potential
      ecological risks on sediments in Baiyangdian Lake, 0-14 cm surface sediments had
      been collected by the no-disturbance-gravity sampler at seven representative
      sampling points of Baiyangdian Lake. Optimized BCR sequential extraction
      procedure was used to carry out the analysis of heavy metal forms in the surface
      sediments. The heavy metal contents of different forms and in different depths
      were determined. The relationship between different forms of heavy metal and
      total organic carbon (TOC) in the sediments was analyzed. The geo-accumulation
      index (Igeo) was employed to evaluate the extent of heavy metal contamination.
      The results demonstrated that Co, Fe, Mn, Pb, Zn were mainly in residual form,
      acid soluble form, Fe-Mn oxide and organic matter bound forms respectively. The
      tendency of organic bound form of heavy metals and TOC of sediments was greater
      than the others. The concentration of Co, Pb, Zn decreased with the increase of
      sediment depth, with the maximal concentration was between 0-2 cm, while the
      concentration of Mn was the minimal between 6-8 cm and the maximal was at 14 cm.
      Baiyangdian sediments were not contaminated as a whole by Co, Mn, apart from
      medium pollution in the entrance of the Fuhe River. The other regions were
      lightly polluted by Zn and Pb.

PMID- 23002617
TI  - [AVS concentrations in Xinan Creek and the influencing factors].
AB  - Sediment and overlying water samples were collected at 10 sampling stations at
      Xinan Creek, a tidal river in Pearl River Delta, and analyzed for physical and
      chemical characteristics as well as microbial incicators, in order to reveal the
      main factors dominating the spatial distribution of acid volatile sulfide (AVS).
      The effects of Eh, SRB OC and TS on the spatial distribution of AVS were
      investigated and the impact of AVS on the toxicity of heavy metals in the studied
      area was evaluated. The results showed that the range of AVS was 0.207-41.453
      micromol x g(-1), with an average of 6.684 micromol x g(-1), which is relatively
      high compared to the results in other studies. The AVS value of the surface layer
      was higher than the bottom layer in 5 stations. The AVS values in both the
      surface layer and the bottom layer were highly variable, the coefficients of
      variation being 93.61% and 153.09% , respectively. The analytical results
      revealed that TS was the factor with the greatest impact on the spatial
      distribution of AVS, and the order was TS > OC > Eh > SRB. Potential ecological
      risk of heavy metals existed in 60% of the smpling stations based on the value of
      Sigma (SEM5-AVS), however, with the criterion of [Sigma(SEM5-AVS)]/foc, none of
      them had inacceptable ecological risk. Furthermore, in terms of single species of
      heavy metals, there was certain risk of toxic effect for all the five heavy
      metals (Cd, Ni, Cu, Zn and Pb). The above mentioned results will provide valuable
      data for the in-depth study of the formation mechanism of AVS and helpful
      reference for environmental impact assessment and scientific rehabilitation of
      heavy metals in polluted rivers.

PMID- 23002618
TI  - [Mechanism of NH(4+)-N removal in drinking water biofilter].
AB  - In order to explore the mechanism of NH(4+)-N removal in drinking water
      biofilter, water quality parameters, such as NH(4+)-N, NO(2-)-N, NO(3-)-N, total
      phosphorus, permanganate index, nitrogen gas, temperature and dissolved oxygen
      etc, were determined in the inflow and outflow of biofilter. Samples of granular
      activated carbon (GAC) at different height (0, 10, 20, 40, 60 cm) of the biofiter
      media were collected and analyzed for the bacterial community with molecular
      biology techniques. The bacterial diversity in the activated carbon biofilm
      sample was studied based on the phylogenetic analysis of sequences. The results
      showed that there were three stages according to the NH(4+)-N concentration in
      the influent. The "nitrogen loss" phenomenon (total inorganic nitrogen in the
      effluent was less than that in the influent) occurred at the first, second and
      third stages and the amount of nitrogen loss were 0.94, 0.32 and 0.15 mg x L(-1),
      respectively. The amount of nitrogen loss had a good positive correlation with
      the NH(4+)-N concentration in the influent, but not a linear relationship with
      the concentration of the permanganate index in the influent. The average
      concentrations of N2 increased gradually with the height of media in the
      biofilter, with values of 14.04 and 14.67 mg x L(-1) in the influent and the
      effluent, respectively. Based on the sequencing results, the ammonia-oxidizing
      bacteria (AOB) in the activated carbon biofilm were classified into three common
      genera: Nitrosococcus, Nitrosomonas and Nitrosospira. When the NH(4+)-N
      concentration in the influent was relatively high, the "nitrogen loss" phenomenon
      in biofilter was caused by the AOB.

PMID- 23002619
TI  - [Characterization and thermodynamic properties of Cu(II) imprinted chitosan
      crosslinked membrane].
AB  - A new type of Cu(II)-imprinted chitosan crosslinked membrane (IM Cu(II)-E-CTS)
      was prepared via molecular imprinting technology, chemical pre-crosslinking and
      crosslinking methods for treatment of wastewater containing low concentration of
      copper ion. IM Cu(II)-E-CTS was characterized by porosity, swelling ratio, amino
      group content, surface morphology, functional group and crystallinity. The
      thermodynamic properties of Cu (II) adsorption on the as-synthesized membrane at
      the low concentration (20-70 mg x L(-1)) were studied. It is found that porosity,
      swelling ratio and amino group contents of IM Cu(II)-E-CTS are 76.9%, 109% and
      4.26 mmol x g(-1), respectively. Compared to the pristine chitosan membrane
      (CTS), 44.0% lower swelling ratio, 528% higher of porosity, 16.5% lower of amino
      group content are found with IM(Cu) (II)-E-CTS. Compared to crosslinked chitosan
      membranes (E-CTS), 24.6% higher amino group content is found with IM(Cu) (II)-E
      CTS. Compared to CTS and E-CTS, the membrane morphology of IM Cu(II) E-CTS has
      undergone significant changes, and the internal structure became loose. Compared
      with CTS, molecular chain of IM Cu(II)-E-CTS is irregular and its crystallinity
      ability is lowered. IM Cu(II)-E-CTS adsorbs more Cu(II) than that of the other
      two metal cations [Ni(II) and Zn(II)]. The adsorption of copper ion on IM Cu(II)
      E-CTS for 20-70 mg x L(-1) of initial Cu(II) concentration follows the Freundlich
      adsorption isotherm (R2 > 0.99). The adsorption is a spontaneous, exothermic, and
      entropy-decreased process.

PMID- 23002620
TI  - [Studies on the degradation of paracetamol in sono-electrochemical oxidation].
AB  - A novel lead dioxide electrodes co-doped with rare earth and
      polytetrafluoroethylene (PTFE) were prepared by the electrode position method and
      applied as anodes in sono-electrochemical oxidation for pharmaceutical wastewater
      degradation. The results showed that the APAP removal and the mineralization
      efficiency reached an obvious increase, which meant that the catalytic efficiency
      showed a significant improvement in the use of rare-earth doped electrode. The
      effects of process factors showed that the condition of the electrode had the
      best degradation efficiency with doped with Ce2O3 under electrolyte concentration
      of 14.2 g x L(-1), 49.58 W x cm(-2), 50 Hz, pH = 3, 71.43 mA x cm(-2). The APAP
      of 500 mg x L(-1) removal rate reached 92.20% and its COD and TOC values declined
      to 79.95% and 58.04%, the current efficiency reached 45.83% after degradation
      process for 2.0 h. The intermediates were monitored by the methods of GC-MS,
      HPLC, and IC. The main intermediates of APAP were p-benzoquinone, benzoic acid,
      acetic acid, maleic acid, oxalic acid, formic acid etc, and the final products
      were carbon dioxide and water. The goal of completely degradation of pollutant
      was achieved and a possible degradation way was proposed.

PMID- 23002621
TI  - [Study on treatment of methylene blue wastewater by fly ash adsorption-Fenton and
      thermal regeneration].
AB  - The physicochemical properties of water-washed fly ash (FA) and acid modified fly
      ash (M-FA) were investigated. The adsorption of methylene blue by FA and M-FA
      were studied by batch experiments. Two methods, Fenton-drive oxidation
      regeneration and thermal regeneration, were used for regeneration of the used FA
      and M-FA. The result showed that the rate of adsorption process followed the
      second order kinetics and the adsorption followed Langmuir isotherms. The
      adsorption equilibrium time was 30 min, and the equilibrium adsorption capacity
      of FA and M-FA were 4.22 mg x g(-1) and 5.98 mg x g(-1) respectively. The
      adsorption capability of M-FA was higher than that of FA. In the range of pH 2
      12, the adsorption capacity of M-FA increased with the increase of pH, whereas
      the adsorption capacity of FA decreased slowly until the pH 8 and then increased.
      Electrostatic adsorption was the major factor on the adsorption capacity. Around
      61% and 55% percentage regeneration (PR) were obtained for FA and M-FA
      respectively when 78.4 mmol x L(-1) H2O2 and 0.72 mmol x L(-1) Fe2+ were used.
      When the condition of thermal regeneration was 400 degrees C and 2 h, a positive
      correlation can be found between the PRs of FA and regeneration times, the PRs
      were 102%, 104% and 107% in three cycles of adsorption-thermal regeneration
      process. However a negative correlation can be found between the PRs of M-FA and
      regeneration times, the PRs were 82%, 75% and 74% in three cycles of adsorption
      thermal regeneration process. The PR of FA was higher than that of M-FA, and
      thermal regeneration was superior to Fenton-drive regeneration.

PMID- 23002622
TI  - [Electricity generation performance of two-chamber microbial full cell in the
      treatment of simulated wastewater].
AB  - The start-up procedures, the degradation efficiency of organics at the anode and
      the removal efficiency of Cu2+ at the cathode of the cell were studied, based on
      which the performance of MFC (microbial fuel cell) in electricity generation and
      wastewater treatment was evaluated. A simple two-chamber microbial fuel cell was
      established with simulated molasses wastewater as substrate at the anode and
      simulated electroplating wastewater as an electron acceptor at the cathode. The
      results from a batch of experiments showed that the highest voltage output of
      417.00 mV was obtained at an external resistance of 800 Omega, and that the
      maximum power density of 44.17 mW x m(-2) was obtained with an internal
      resistance of 293 Omega based on the polarization curve. In addition, COD removal
      rate reached its highest value (47.31%) in the fifth cycle, and the maximum
      removal rate (59.76%) for Cu2+ was recorded in the fourth cycle. In summary, the
      application of MFC in the treatment of organic wastewater and electroplating
      wastewater is feasible.

PMID- 23002623
TI  - [Preparation and characterization of Zn/Cr-LDHs and their removal performances of
      reactive brilliant orange X-GN].
AB  - Zn/Cr-LDHs with cationic ratios of 1:1 to 1:5 were prepared using the co
      precipitation method. After preparation of the layered double hydroxides, 2:1
      Zn/Cr-LDHs were calcined at 300, 400 and 500 degrees C in a Muffle furnace for 2
      h. The obtained mixed oxides are also called calcined layered double hydroxides
      (Zn/Cr-LDO). Structures of the obtained materials were characterized by powder X
      ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, atomic
      absorption spectrometry and BET analysis. Experiments were then carried out to
      investigate the removal of reactive brilliant orange X-GN by 2:1 Zn/Cr-LDHs and
      Zn/Cr-LDO under ultraviolet light and in dark conditions. The results showed that
      the removal capacity of 2:1 Zn/Cr-LDHs was not affected by ultraviolet light.
      Under the irradiation of ultraviolet light, the removal rate of reactive
      brilliant orange X-GN by Zn/Cr-LDO was twice as high as that in dark conditions,
      which demonstrated its photocatalysis property and its removal of reactive
      brilliant orange X-GN by the combined action of absorption and photocatalysis.

PMID- 23002624
TI  - [Transport processes of low-level radioactive liquid effluent of nuclear power
      station in closed water body].
AB  - The transport processes of low-level radioactive liquid effluent of Xianning
      nuclear power station in the closed water body Fushui Reservoir are simulated
      using the EFDC model. Six nuclides concentration distribution with different half
      lives in the reservoir are analyzed under the condition of 97% guarantee rate
      incoming water and four-running nuclear power units. The results show that the
      nuclides concentration distribution is mainly affected by the flow field of the
      reservoir and the concentration is decided by the half-lives of nuclide and the
      volume of incoming water. In addition, the influence region is enlarged as
      increasing of half-life and tends to be stable when the half-life is longer than
      5 years. Moreover, the waste water discharged from the outlet of the nuclear
      power plant has no effect on the water-intake for the outlet located at the
      upstream of the water-intake and the flow field flows to the dam of the
      reservoir.

PMID- 23002625
TI  - [Analysis of carbon balance and study on mechanism in anoxic-oxic-settling
      anaerobic sludge reduction process].
AB  - In order to deeply explore the mechanism of sludge reduction in OSA system,
      carbon balance was performed in an anoxic-oxic-settling-anaerobic (A + OSA)
      system and a reference AO system to investigate effects of inserting a sludge
      holding tank in sludge cycle line on the sludge reduction process. Meanwhile,
      carbon mass change in each reaction unit was identified in terms of solid, liquid
      and gas phases. The causes of excess sludge reduction in A + OSA system were
      deduced. The carbon balance results show that when the hydraulic retention time
      in the sludge holding tank is 7.14 h, carbon percent in solid phase of the sludge
      reduction system is nearly 50% higher than that of the reference system,
      supporting the consequence that sludge reduction rate of 49.98% had been
      achieved. The insertion of a sludge holding tank in the sludge return circuit can
      be effective in sludge reduction. Carbon changes in each unit reveal that the
      amount of carbon consumed for biosynthesis in the anoxic and oxic tanks (main
      reaction zone) of the sludge reduction system is higher than in that of the
      reference system. Sludge decay is observed in the sludge holding tank.
      Furthermore, CH4 released from the sludge holding tank is significantly higher
      than that from the main reaction zone. The DGGE profiles show that there are
      hydrolytic-fermentative bacteria in the sludge holding tank related to sludge
      decay. The excess sludge reduction in the A + OSA system could be a result of the
      combination of sludge decay in the sludge holding tank and sludge compensatory
      growth in the main reaction cell.

PMID- 23002626
TI  - [Effect of mixed carbon sources in the granulation process of EBPR system].
AB  - Activated sludge highly enriched of phosphorus accumulating organisms (PAOs) were
      seeded, and cultivated with mixed carbon sources of different propionate to
      acetate ratios, to obtain granule-based enhanced biological phosphorus removal
      (EBPR) system. The results showed that the granule growth rate was obviously
      increased as the proportion of propionate in the mixed carbon sources increased.
      After operating for 90 d, the volume average particle diameters of the mature
      granules were 550.64 microm, 599.41 microm, 642.38 microm, 680.99 microm and
      745.08 microm, and the sludge volume indexes (SVI) of the mature granules were 30
      mL x g(-1), 40 mL x g(-1), 50 mL x g(-1), 60 mL x g(-1) and 75 mL x g(-1), in the
      treatment of 0%, 25%, 50%, 75% and 100% propionate in mixed carbon sources,
      respectively. The phosphorus (P) removal performances of granule-based EBPR
      system cultivated with different carbon sources showed significant differences
      under the same P-loading. It was about 0.78 mg x g(-1), 2.29 mg x g(-1), 2.96 mg
      x g(-1), 3.23 mg x g(-1) and 3.77 mg x g(-1) of net P removed in the treatment of
      0%, 25%, 50%, 75% and 100% propionate in mixed carbon sources, respectively,
      which resulted in the phosphorus removal efficiencies were 31.5%, 56.5%, 77.4%,
      85.9% and 97.0%, respectively.

PMID- 23002627
TI  - [Biocatalyst of redox mediators on the denitrification by Paracoccus versutus
      strain GW1].
AB  - The quinone respiration process of Paracoccus versutus strain GW1 was
      characterized and the effects of the four redox mediators on the denitrification
      process were studied. The experiment results suggested that quinones were
      utilized by Paracoccus versutus strain GW1 as electron acceptors in the
      respiratory chain and reduced to hydroquinone. Batch experiments were carried out
      to investigate the biocatalyst effect of redox mediators as catalyst on the
      denitrification process at 35 degrees C. All four redox mediators tested were
      able to enhance the nitrate removal efficiency and the denitrification efficiency
      by 1.14-1.63 fold and 1.12-2.02 fold, respectively. The accelerating effect from
      high to low was AQDS > 1,5-AQDS > AQS > alpha-AQS. In the presence of redox
      mediators, the stabilized ORP values in the nitrate decomposition process were
      reduced by 33-75 mV. The pH variations in denitrification with redox mediators
      showed similar tendency to that of the conventional nitrate removal process. In
      the concentration range of 0-0.32 mmol x L(-1), AQDS had the best accelerating
      effect and a linear correlation was found for the denitrification rate K and the
      AQDS concentration cAQDS. This study indicated that the application of redox
      mediators significantly improved the denitrification process by enhancing the
      decomposition rate.

PMID- 23002628
TI  - [Isolation of a high hydrogen-producing mutant TB34 generated by transposon
      insertion and analysis of hydrogen production].
AB  - To increase the hydrogen-producing capacity of Pantoea agglomerans BH18, isolated
      from mangrove sludge, we constructed a stable transposon mutagenesis library of
      this strain. A Tn7-based transposon was randomly inserted into the genomic DNA.
      Mutants were screened by kanamycin resistance and identified by amplification of
      the inserted transposon sequences. A mutant strain TB34 was isolated, whose
      hydrogen production capacity was significantly improved compared to the wild type
      strain. In seawater-containing medium supplemented with 10 g x L(-1) glucose and
      had an initial pH of 7.0, the hydrogen yield (H2/glucose) of the mutant strain
      was (2.04 +/- 0.04) mol x mol(-1), which was 43% higher than that of the wild
      type strain. The mutant TB34 showed steady hydrogen production capacity for five
      consecutive passages. Different carbon sources were tested in the hydrogen
      production by the mutant TB34 and the results showed that both the mutant strain
      TB34 and the wild type strain BH18 were able to produce hydrogen on sucrose,
      glucose and fructose. However, different from the wild type strain, the mutant
      strain TB34 was also able to produce hydrogen using xylose as substrate, with a
      hydrogen yield (H2/xylose) of (1.34 +/- 0.09) mol x mol(-1), indicating a broader
      substrate spectrum in the mutant.

PMID- 23002629
TI  - [Condition optimization for degradation of chlorophenols using laccase from
      Amillariella mellea].
AB  - Crude laccase extracted from the Amillariella mellea fermentation broth was
      directly used to catalyze the degradation of 2,4-chlorophenol (2,4-DCP) and 2
      chlorophenol (2-CP). The effects of reaction time, pH, temperature, chlorophenol
      concentration, and laccase dosage on the removal efficiency of chlorophenols were
      investigated. Optimal catalytic conditions for the degradation of chlorophenols
      were obtained and the degradation kinetics were analyzed. The results indicated
      that the crude laccase from Amillariella mellea was able to effectively degrade
      2,4-DCP and 2-CP, with higher catalytic ability towards 2,4-DCP degradation. For
      2,4-DCP degradation, the optimal temperature was 40 degrees C, the optimal
      substrate concentration was 75 mg x L(-1), the optimal enzyme dosage was 0. 1 U x
      mL(-1), and the optimal pH was 6.5. Under these conditions, the maximum
      degradation rate of 2,4-DCP reached > 97% after 10 h. For 2-DCP degradation, the
      optimal temperature was 50 degrees C, the optimal substrate concentration was 100
      mg x L(-1), the optimal enzyme dosage was 0.1 U x mL(-1), and the optimal pH was
      6. Under these conditions, the maximum degradation rate of 2-CP was over 93%
      after 10 h. The reaction process of laccase-catalyzed 2,4-DCP and 2-CP
      degradation obeyed the first-order kinetics equation. The laccase from
      Amillariella mellea was able to effectively degrade chlorophenols, indicating its
      potential application value in phenolic pollutant control and environmental
      protection.

PMID- 23002630
TI  - [Characterization of CH4, N2O emission and selection of rice cultivars in double
      cropping rice fields].
AB  - Methane and nitrous oxide emission fluxes of rice cultivars in the double
      cropping rice fields were measured by static chamber-gas chromatography in field
      experiments. The results showed a single-peak pattern in seasonal variations of
      methane emission and a double-peak pattern in variations of nitrous oxide
      emission for the early season rice, and a single-peak pattern in variations of
      both methane and nitrous oxide emission for the late season rice. There was
      significant difference among the rice cultivars in the average emission fluxes of
      methane and nitrous oxide during the whole growing season. The ranges for the
      methane and nitrous oxide average emission fluxes were 0.58 mg x (m2 x h)(-1) and
      5.89 microg x (m2 x h)(-1) for the early-season rice cultivars, and 4.06 mg x (m2
      x h)(-1) and 5.70 microg (m2 x h)(-1) for the late-season rice, respectively. The
      ranges of GWP (global warming potential) contributed by the amount of greenhouse
      gases emission and GWP per unit yield of rice cultivars were 2.92 kg x hm(-2) and
      0.097 kg x kg(-1) for the early-season rice cultivars, and 2 256 kg x hm(-2) and
      0.28 kg x kg(-1) for the late-season rice cultivars, respectively. The GWP and
      GWP per unit yield of rice types were sorted in a descending order: traditional
      rice > the super hybrid rice > the hybrid rice. For the early season rice, the
      methane and nitrous oxide emission fluxes of the blank region without rice were
      27.1%-31.8% and 33.6%-88.3% of those measured for the region with rice planted,
      respectively, whereas the corresponding percentages for the late season rice were
      23.8%-28.8% and 38.6%-45.3%, respectively. Based on these results, Luliangyou No.
      819, Jinyou No. 402 and Xiangzaoxian No. 24 were selected as suitable early
      season rice cultivars, whereas Yueyou No. 9113 and Xiangwanxian No. 12 should be
      chosen for late-season rice planting.

PMID- 23002631
TI  - [Short-term effects of exogenous nitrogen on CH4 and N2O effluxes from Cyperus
      malaccensis marsh in the Min River estuary].
AB  - Using static chamber-GC techniques, the short-term effects of nitrogen input on
      the emission fluxes of CH4 and N2O from a Cyperus malaccensis wetland were
      determined. The results showed that the emission of CH4 was increased by high
      nitrogen input at all sampling times, whereas the low nitrogen input exhibited
      different variation characteristics at different time points. Compared to the
      control treatment, the CH4 emission flux in the two nitrogen input treatments
      (N1, N2) was increased by -44.35%-1 057.35% and 7.15%-667.37%, respectively. The
      input of exogenous nitrogen had positive priming effect on N2O emission flux
      within 24 hours, increased by up to 171.60 folds and 177.79 folds, respectively.
      After 8 days, the priming effect by the nitrogen input weakened or disappeared.
      There was no significant effect of nitrogen input on the Ec, pH and Eh of soil at
      different depths in the salt marsh during the experiment. In the control
      treatment, the CH4 emission flux was negatively correlated solely with Eh of soil
      at 5 cm depth, whereas in the N1 treatment, it was negatively correlated solely
      with soil temperature at 10 cm depth. In the N2 treatment, there was negative
      correlation between the CH4 emission flux and Ec of soil at 5cm depth, pH of soil
      at 0, 5 cm depths, and Eh of soil at 0, 5, 10 cm depths. However, no significant
      correlation between the N2O emission flux and the environmental variables in the
      wetland was found. This study indicated that the temporal variability should be
      taken into consideration when examining the effects of nitrogen input on the
      emission of greenhouse gases in the wetlands.

PMID- 23002632
TI  - [Temporal-spatial variations of total nitrogen in the degraded grassland of Three
      River Headwaters region in Qinghai Province].
AB  - Based on the data of the second soil survey and field sampling in 2009 and 2010,
      temporal-spatial variations of total nitrogen (TN) in the degraded grassland 0-10
      cm, 10-20 cm and 30-50 cm beneath the surface soil at the Three-River Headwaters
      region in Qinghai Province for a 30-year period (1980-2010) were evaluated using
      geostatistics and geographic information system (GIS). After exclusion of the
      outliers, the results showed a downward trend from the surface to the bottom in
      the mean TN values measured in the samples collected during the two periods. For
      the same soil layers, the average TN contents and the coefficient of variation in
      1980 were higher than those in 2010. The TN contents of the two periods showed a
      log-normal distribution. Semivariograms analysis of the experiments indicated
      that the nugget effect in the same soil layer was lower in 2010 than in 1980;
      suggesting that the spatial distribution autocorrelation of TN in the Three-River
      Headwaters region in Qinghai Province was strengthened and structural factors
      played a more and more important role on the spatial distribution of TN. The
      results of ordinary kriging showed that there were regional differences in
      variations of the total nitrogen content. There were significant decreases in the
      southern, central and eastern regions, while the increase mainly occurred in the
      western areas.

PMID- 23002633
TI  - [Temporal variations of clay content in eroded sediment under different rainfall
      condition].
AB  - Erosion and sediment characteristics were measured using simulated rainfall on
      two cultivated soils from the Loess Plateau, China. The size distribution of
      eroded sediment (non-dispersed) was compared with equivalent measurements of the
      same samples after chemical and mechanical dispersion(dispersed) to investigate
      the aggregation ratio (AR) and enrichment ratio (ER). Results show that clay
      content is increasing with the length and rainfall intensity. The loessial soil
      increased by 8.77% and 2.43%, but the Lou soil increased by only 2.76% and 0.4%.
      With the increase of slope, the clay content of the two loess reduced by 4.91%
      and 3.93%, respectively. AR values were less than 1 and ER values were greater
      than 1. These indicated that relatively slight clay dispersion occurred and that
      most of the clay in the sediments was in the form of aggregates. The results will
      improve understanding of erosion and sedimentation processes, which in turn will
      improve erosion modeling. Knowledge of temporal variations of clay in sediment
      can also provide the basis for understanding and modeling the transfer of
      nutrients on hillslope.

PMID- 23002634
TI  - [Effects of soil properties on the stabilization process of cadmium in Cd alone
      and Cd-Pb contaminated soils].
AB  - In order to clarify the effects of soil properties on the stabilization process
      of the cadmium (Cd) added, 11 different soils were collected and incubated under
      a moisture content of 65%-70% at 25 degrees C. The changes of available Cd
      contents with incubation time (in 360 days) in Cd and Cd-Pb contaminated
      treatments were determined. The stabilization process was simulated using dynamic
      equations. The results showed that after 1.0 mg x kg(-1) Cd or 500 mg x kg(-1) Pb
      + 1.0 mg x kg(-1) Cd were added into the soil, the available Cd content decreased
      rapidly during the first 15 days, and then the decreasing rate slowed down, with
      an equilibrium content reached after 60 days' incubation. In Cd-Pb contaminated
      soils, the presence of Pb increased the content of available Cd. The
      stabilization process of Cd could be well described by the second-order equation
      and the first order exponential decay; meanwhile, dynamic parameters including
      equilibrium content and stabilization velocity were used to characterize the
      stabilization process of Cd. These two key dynamic parameters were significantly
      affected by soil properties. Correlation analysis and stepwise regression
      suggested that high pH and high cation exchange capacity (CEC) significantly
      retarded the availability of Cd. High pH had the paramount effect on the
      equilibrium content. The stabilization velocity of Cd was influenced by the soil
      texture. It took shorter time for Cd to get stabilized in sandy soil than in the
      clay.

PMID- 23002635
TI  - [In-situ remediation of polychlorinated biphenyls polluted soil by ecological
      controlling measures: a field trial].
AB  - A field experiment was conducted to study the remediation of agricultural soils
      polluted with polychlorinated biphenyls (PCBs) by several ecological controlling
      measures. After sequential stages of liming, plowing, planting alfalfa and paddy,
      a significant part of PCBs was removed from the soil, with an average removal
      rate of 86.9%. The treatment also decreased the toxic equivalency of dioxin-like
      PCBs in soil. Analysis of PCB congener composition showed that at stages of
      liming, plowing and alfalfa planting, the low-chlorinated biphenyls were removed;
      whereas at the stage of paddy planting, the high-chlorinated biphenyls were
      degraded. The ecological controlling measures had little influence on the
      microbial communities in soil. The results suggest that ecological control
      techniques could be widely applied in the remediation of agricultural soils with
      PCBs contamination.

PMID- 23002636
TI  - [Characterization comparison of polycyclic aromatic hydrocarbon uptake by roots
      of different crops].
AB  - It is important to investigate the differences in polycyclic aromatic hydrocarbon
      (PAH) uptake by roots of different crops for selecting and breeding less or
      excess uptake species of PAHs by genetic engineering, and further yielding safe
      production and phytoremediating the soil or water contaminated with PAHs.
      Hydroponic experiments were performed to study characterization comparison of
      phenanthrene (a representative of PAHs) uptake by soybean, wheat and carrot
      roots. Soybean, carrot and wheat roots can take up phenanthrene from Hoagland
      nutrient solution and the phenanthrene absorbed by roots increases with
      incubation time. The uptake process consists of two sequential phases: a fast
      accumulation process followed by a slow one. The capability to take up
      phenanthrene for the three crops can be arranged as soybean > carrot > wheat. The
      relationship between the phenanthrene absorbed and time fits Elovich equation
      well. Uptake rate constants for soybean, carrot and wheat roots are 4.31, 4.10
      and 2.84 mg x (kg x h)(-1), respectively. Concentration-dependent uptake of
      phenanthrene by roots of soybean, carrot and wheat can be described with
      Michaelis-Menten equation and the Km values for soybean, carrot and wheat are
      0.117, 0.124 and 0.540 mg x L(-1). Hydroponic solution pH increases due to
      phenanthrene uptake and the trend in pH increase significantly correlates with
      those in uptake rate constant and Km value. In addition, the orders of uptake
      rate constant, Km value and pH increase for soybean, carrot and wheat are the
      same as that of uptake capability. Therefore, it is concluded that uptake rate
      constant, Km value and pH increase can be employed as indicators for the
      capability to take up PAHs by crop roots, and uptake rate constant and Km value
      are better indicators than pH increase because of less affecting factors.

PMID- 23002637
TI  - [Characteristics and mechanism of sodium removal by the synergistic action of
      flue gas and waste solid].
AB  - The carbon dioxide (CO2) in flue gas was used to remove the sodium in the red mud
      (RM) , a kind of alkaline solid waste generated during alumina production. The
      reaction characteristics and mechanism of sodium removal by the synergistic
      action of CO2 and RM were studied with different medium pH, reaction time and
      temperature. It was demonstrated that the remove of sodium by RM was actually the
      result of the synergistic action of sodium-based solid waste in RM with the CO2
      H2O and OH(-)-CO2 systems. The sodium removal efficiency was correlated with pH,
      reaction temperature and time. The characteristics of RM before and after sodium
      removal were analyzed using X-ray diffractometer (XRD) and scanning electron
      microscope (SEM), and the results showed that the alkaline materials in the red
      mud reacted with CO2 and the sodium content in solid phases decreased
      significantly after reaction. The sodium removal efficiency could reach up to 70%
      with scientific procedure. The results of this research will offer an efficient
      way for low-cost sodium removal.

PMID- 23002638
TI  - [Decomposition model of energy-related carbon emissions in tertiary industry for
      China].
AB  - Tertiary industry has been developed in recent years. And it is very important to
      find the factors influenced the energy-related carbon emissions in tertiary
      industry. A decomposition model of energy-related carbon emissions for China is
      set up by adopting logarithmic mean weight Divisia method based on the identity
      of carbon emissions. The model is adopted to analyze the influence of energy
      structure, energy efficiency, tertiary industry structure and economic output to
      energy-related carbon emissions in China from 2000 to 2009. Results show that the
      contribution rate of economic output and energy structure to energy-related
      carbon emissions increases year by year. Either is the contribution rate of
      energy efficiency or the tertiary industry restraining to energy-related carbon
      emissions. However, the restrain effect is weakening.

PMID- 23002639
TI  - [Molecular etiology analysis among students with profound hearing loss in a
      special education school in Yangzhou].
AB  - OBJECTIVE: To study molecular epidemiological basis of non-syndromic hearing loss
      in Yangzhou area. METHOD: The selected objects were 90 severe non-syndrome
      deafness students in special education schools in Yangzhou city, Jiangsu
      province. The deafness gene chip diagnostic kit was used for screening the nine
      hot spots mutations in four common deafness-related genes in Medical Testing
      Center of Northern Jiangsu People's Hospital. These nine hot spots gene mutations
      included GJB2 (35 delG, 176 del16, 235 delC and 299 delAT) GJB3 (538C > T),
      SLC26A4 (IVS7-2A > G, 2168A > G) and mtDNA 12S rRNA (A > G,1494C > T) mutation
      detection by line. RESULT: In 90 patients, 64 patients were found to carry
      deafness mutations by using gene chip diagnostic kit (the rate of mutation was
      71.7%) GJB2 gene mutation in 40 cases (44.4%)which included 235 delC homozygous
      in 20 (22.2%) cases, 235 delC single heterozygous mutation in 4 cases (4.4%)and
      235 delC and 299 delAT compound heterozygous mutations in 2 case (2.2%)
      separately. 299 delAT single heterozygous mutation in 2 case (2.2%), 299 delAT
      simple mutation in 2 case (2.2%). 176 del16 heterozygous mutations in 2 case, 176
      del16 homozygous mutation in 2 case (2.2%). 176 del16 heterozygous mutations, and
      235 del C heterozygous mutation in 6 cases (6.7%). SLC26A4 gene mutations in 22
      cases (24.4%),which included IVS7-2A > G homozygous in 2 (2.22%) cases, IVS7-2A >
      G and 2168A > G compound heterozygous mutations in 2 cases (2.2%), IVS7-2A > G
      single heterozygous mutation in 18 cases (20.2%), and mtDNA 12S rRNA A > G
      mutation in 2 cases (2.2%), GJB3 mutations were not detected. CONCLUSION: The
      deafness gene diagnostic techniques is worth applying for screening and
      diagnosis.

PMID- 23002640
TI  - [Epidemiological studies on mtDNA 12S rRNA A1555G mutation of 10 non syndromic
      hearing loss families in Yunnan province].
AB  - OBJECTIVE: To investigate the meaning of the mutation screening, prevalence,
      inheritance and the intervention or the prevention for the specific drugs in 10
      families with non-syndrome hearing loss in Yunnan Province, China. METHOD: To do
      a questionnaire about the cases of ten families with non-syndrome hearing loss
      and to draw a detailed matriarchal family tree detailed. Following that, the
      A1555G mutation-positive individuals were detected and confirmed using DNA
      extracting, PCR amplification and sequencing for family volunteer. RESULT: There
      are 96 members have attended the blood collection in these ten families. Thirty
      six of them had the normal hearing and 60 of them had the sensory neural hearing
      loss. However, 4 out of those had no A1555G point mutation, and 92 had A1555G
      point mutation (95.8%). While 7 of those were Heterogeneity, the rest were all
      homogeneous mutation. There were also 73 patients who had amino glycoside
      antibiotic medication history. However all the rest cases had a history of amino
      glycoside antibiotic medication were not clear yet. CONCLUSION: The proportion of
      patients with drug-induced deafness is high in Yunnan province and the mutation
      rate of mitochondrial DNA A1555G is also high. It is worthy to do DNA 12SrRNA
      A1555G mutation screening for drug intervention and prevention.

PMID- 23002641
TI  - [PCR-GeneScan technique for detection of the GJB2 235 delC and mtDNA A1555G
      mutations for hereditary hearing loss].
AB  - OBJECTIVE: To develop a molecular genetic assay to detect the GJB2 235 delC and
      mtDNA A1555G mutations simultaneously based on fluorescent labeled multiplex PCR
      and automatic DNA fragment analyzing techniques. METHOD: One hundred and twenty
      samples were pooled in our experiment to test the feasibility of new method. The
      PCRs were performed and the size fragment of PCR products were analyzed on ABI
      3100 Genetic Analyzer. Data analysis were taken using the software package of
      GeneScan and GeneMarker. RESULT: Seventeen samples of DNA with 235 delC and 17
      samples with A1555G were tested using this protocol. A false-positive sample
      without GJB2 235 delC mutation was tested. CONCLUSION: This assay can detect both
      mutations in pooled DNA tests and will be a useful tool for newborn screening and
      carrier screening for the hereditary hearing loss in Chinese population.

PMID- 23002642
TI  - [A literature review of epidemiological studies on mutation hot spots of Chinese
      population with non-syndromic hearing loss].
AB  - OBJECTIVE: To identify the regional mutation hot spots characteristics, and then
      to establish a regional genetic screening programs. METHOD: Molecular
      epidemiological literatures about Chinese deafness gene GJB2, SLC26A4,
      mitochondrial DNA mutations from 2006 to the first half of 2011 were retrieved in
      Wanfang and Pubmed literature database. The primary data of these studies
      including the number of samples, demographic characteristics, mutation
      frequencies and so on,were analyzed statically. RESULT: Of 46 papers, 42 were
      included in this study. The patients all had non-syndromic sensorineural hearing
      loss and lived in 20 regions of China. A total of 18094 were counted and the
      average mutation frequencies were approximately 42.0%. The mutation frequencies
      of 235 delC were 16.34%, 299-300 delAT were 4.75% in GJB2 gene and IVS7-2A > G
      were 12.60%, 2168A > G were 2.32% in SLC26A4 gene and the mutation frequencies of
      1555A > G, 1494C > T in mtDNA were 5.21%, 1.11% respectively. The statistical
      discrepancy was significant among mutation frequencies in different regions by
      chi2-test (P < 0.05). CONCLUSION: Molecular epidemiological statistics show that
      the 6 locus are the mutation hot spots in Chinese people with non-syndromic
      hearing loss and can be used for genetic screening according to the specific
      regional mutation characteristics.

PMID- 23002643
TI  - [Effect of age at cochlear implantation on auditory performance at the early
      stage after surgery in infants].
AB  - OBJECTIVE: To evaluate the auditory performance of infants with cochlear implants
      at the early stage after surgery, summarize the development of auditory ability,
      investigate the effect of age at cochlear implantation on auditory performance
      within the first year after surgery and provide a reference for their
      habilitation program. METHOD: A total of 272 infants with prelingually profound
      hearing loss participated in this study, ranging in age at cochlear implantation
      from 18 to 36 months. The mean age was 21 months with a standard deviation of 7
      months. Infants with cochlear implants were divided into three groups according
      to their age at implantation. Infants in group A were implanted under 18 months
      of age. Infants in group B were implanted between 18 and 24 months of age.
      Infants in group C were implanted between 25 and 36 months of age. Categories of
      auditory performance (CAP) was used to evaluate the auditory performance, which
      rates auditory abilities in eight categories for a scale of 0 to 7. RESULT: The
      mean scores of CAP for all infants at each interval were significantly different
      after implantation. Significant differences were observed in mean scores of CAP
      among these three groups in 1 and 3 months after switch-on. However there were no
      significant differences in pre-operation, 6, 9 and 12 months after switch-on.
      CONCLUSION: There is a significant improvement in auditory performance of infants
      with prelingually profound hearing loss within the first year after cochlear
      implantation. The age at cochlear implantation has no critical influence on the
      development of auditory capabilities at the early stage after surgery. CAP is a
      practical tool which can be used in clinic in China.

PMID- 23002644
TI  - [Plain X-ray for locations of intracochlear electrode arrays during cochlear
      implantation].
AB  - OBJECTIVE: To evaluate the position and shape of inserted electrode arrays by
      plain X-ray during cochlear implantation. METHOD: Cochlear view of implanted
      electrode arrays by plain X-ray were observed during operation in 54 patients
      received cochlear implant. RESULT: The image in cochlear view could provide the
      information about position and shape of inserted electrode arrays. The spiral
      shape electrode arrays without distortion and folding were found in 52 cases. The
      complete insertion of intracochlear electrode in these patients were confirmed by
      surgery. Of 54 cases, the other 2 cases showed improper position and C-shape of
      intracochlear electrodes, one was partial insertion and the other was bending
      inside the cochlea. The bending electrode array was reinserted immediately during
      operation. CONCLUSION: Routine plain X-ray after inserted electrode during
      operation was a best way of knowing the shape and depth of the electrode array,
      especial for the difficult cochlear implantation, and also could avoided
      anesthetization again.

PMID- 23002645
TI  - [CT and MRI study in severe sensorineural hearing loss in children].
AB  - OBJECTIVE: To investigate the value of CT and MRI in diagnosing the children with
      sensorineural hearing loss. METHOD: Ninety-six cases suspected as severe
      sensorineural hearing loss were examined by CT/MRI system and 3D reconstruction.
      RESULT: Of 96 cases, 15 cases were found malformation these malformation included
      Michel, cochlear hypoplasia, commun cavity, Mondini, inner canal straitness,
      cochlear nerve undeveloped and vestibular aqueduct enlargements. CONCLUSION:
      There are 15.63% inner ear malformation occurred in sensorineural hearing loss
      children. CT and MRI of inner ear have a great clinical value in diagnosing
      children sensorineural hearing loss by learning the anatomy.

PMID- 23002646
TI  - [Cultivation and identification of follicular papilla cells from back skin of
      actual rat in vitro].
AB  - OBJECTIVE: To establish more efficient method to isolate of dermal papilla cells
      (DPCs) from back skin of SD rats, and then to study the growth ability and
      characteristics of SD rat dermal papilla cells in vitro. METHOD: DPCs were
      separated from back skin of SD rats according to the modified method of two-step
      enzymatic digestion. The DPCs morphological observation under inverted
      microscope, the growth kinetics by cells number, the cell cycle analysis by flow
      cytometry analysis and determine the surface epitopes by immunohistochemical
      staining and flow cytometry analysis. RESULT: Cultured DPCs were similar to
      fibroblasts in appearance, but generally and periodically exhibited an
      aggregative growth pattern. The growth kinetics showed that the number of DPCs
      presented progressive increase in a logarithm mode in the first 3 days and
      entered into plateau after 9 days, P1, P3, P5 multiplication time was 68 h, 52 h
      and 36 h, respectively. The flow cytometrical analysis showed that DPCs of P1,
      P3, P5 G0/G1 stage were (90.21 +/- 5.13)%, (81.23 +/- 1.85)% and (75.16 +/-
      5.32)%, respectively. G0/G1 stage cells became less following passage subculture
      and elongation of culture time, but most of the DPCs stayed resting stage still.
      The cultivated dermal papilla cells expression of alpha-smooth muscle and CD44 on
      cell surface was positive, CK and CD34 were negative. CONCLUSION: DPCs can be
      separated by the modified method of two-step enzymatic digestion successfully.
      The cultivated dermal papilla cells vitro show the feature of stem cells and has
      important potentially as a new seed cell source for cell engineering.

PMID- 23002647
TI  - [Clinical research of T tube implantation on children with chronic otitis media].
AB  - OBJECTIVE: To study the appropriate time to take out T tube, long-term effect and
      adverse consequence of children with chronic otitis media subjected to
      adenoidectomy and tonsillectomy plus tympanostomy. METHOD: One hundred and
      eighteen children with 226 ears operated were analyzed and summarized. RESULT: T
      tubes taken out at 1, 3, 6 and 12 month were 6, 102, 88 and 23 ears,
      respectively, and T-tubes were not taken out in 7 ears. CONCLUSION: At present,
      the treatment is curable and reliable with fewer complications. The appropriate
      time to take out the T-tube should be 3 months after the operation.

PMID- 23002648
TI  - [Clinical study of 300 patients with subjective tinnitus from collegian].
AB  - OBJECTIVE: To explore the clinical and psychoacoustic characteristics of tinnitus
      patients from university students. METHOD: The study included 300 tinnitus
      patients. All patients were interviewed by the same investigator and using the
      same questionnaire. Data were collected and analyzed. RESULT: Hearing loss was
      seen in 54.3% of the patients. There was no correlation between tinnitus severity
      and tinnitus loudness (P > 0.05). There was a significant relationship between
      high-pitched tinnitus and high-frequency SNHL (P < 0.01). In 86.0% of these
      patients, tinnitus had produced an adverse effect on their psychology and daily
      life. CONCLUSION: There is a significant relationship between high-pitched
      tinnitus and high-frequency SNHL. Tinnitus has an impact on the life of patients
      from the university students.

PMID- 23002649
TI  - [Clinical study of 26 patients with osteoma in the external].
AB  - OBJECTIVE: To summarize the experience of diagnosis and treatment on osteoma in
      the external auditory canal. METHOD: Retrospective study were undertaken in 26
      patients with osteoma in the external auditory canal operated in author's unit.
      RESULT: Osteomas were removed through interauricular approach in all patients and
      confirmed by histopathological examination. The hearing of 22 patients with
      conductive hearing loss became normal after operation. The air conduction hearing
      threshold in 2 patients with mixed hearing loss improved average 15 dB and 20 dB
      respectively after operation. The follow up was more than 1 year, and no
      recurrence or complications had occurred. CONCLUSION: Osteoma in the external
      auditory canal is an uncommon benign lesion. The method of choice in diagnosis is
      temporal bone CT scan. Osteoma must be distinguished from exostosis in the
      external auditory canal. Osteoma is confirmed by pathological diagnosis and
      surgery is the only method for treatment.

PMID- 23002650
TI  - [Treatment and prognosis analysis on 229 cases of sudden deafness].

PMID- 23002651
TI  - [Clinical significance of fistula washing in treatment of congenital preauricular
      fistula].

PMID- 23002652
TI  - [One cases of esophageal cervical spondylosis with pharyngeal foreign body
      sensation].
AB  - The patient was treated as pharyngeal foreign body sensation for six months.
      Laryngeal endoscopy: one about 1 cm x 2 cm x 2 cm, hard, smooth bulge in
      hypopharyngeal wall at the plane of epiglottis valley. The cervical MRI showed
      that the C3-C4 disc herniation and degeneration of the C3-C4 vertebrae. Cervical
      CT showed the C3-C4 disc osteophyte formation and forward bulge. After orthopedic
      consultation, the patient was diagnosed as esophageal cervical spondylosis. C3-C4
      diskectomy and vertebral interbody bone grafted with plate fixation were
      undertaken. At postoperational day 2, the pharyngeal foreign body sensation
      disappeared.

PMID- 23002653
TI  - [A case of clivus chordoma with first appearance of sudden deafness].
AB  - The patient was hospitalized for sudden hearing impairment for one day. PHYSICAL
      EXAMINATION: the blood pressure was 150/90 mm Hg, the tympanic membranes in both
      ears were complete and otopiesis. Audiogram showed total deafness in the right
      ear and slight sensorineural deafness at speech frequency and 80 db for high tone
      air conduction and 70 db for bone conduction at high frequency in left ear.
      Tympanogram showed "A" type in both ears and the ipsilateral and contralateral
      acoustic reflex in both ears were not induced. BAEP showed that the V wave
      threshold on the right was not induced and it was 50 dbnHL on the left. CT showed
      a limited low density area in the clivus. MRI showed a space-occupying lesion
      behind the basilar clivus and ahead of brain stem. Pathological examination
      showed CK(+), EMA(+), S-100(+) according to immunohistochemistry, which was in
      accordance with chondroid chordoma. DIAGNOSIS: chondroid chordoma of clivus.

PMID- 23002654
TI  - [Development of study on NMDA receptor with auditory plasticity and learning
      memory].
AB  - Neural plasticity is one of the most important research area of developmental
      neurobiology. NMDA(N-Methyl-D-aspartate) receptor is one of the glutamate
      receptors in nervous system, which palys an important role in many biological and
      pathological changes, such as development of neural network, neural plasticity,
      learning and memory, degeneration of the neurons and so on. The studies on NMDA
      receptor with auditory plasticity and learning and memory were reviewed in order
      to make early intervention for hearing impaired children and provide a
      theoretical basis.

PMID- 23002655
TI  - Getting to the health system we need.

PMID- 23002656
TI  - Before you answer the phone, read this.

PMID- 23002657
TI  - Memory maker: Clinical management of early and midstage dementia.

PMID- 23002658
TI  - Pairing up: shared decision making in cancer screening.

PMID- 23002659
TI  - UTIs in nursing home residents: better diagnosis would reduce antibiotic overuse.

PMID- 23002660
TI  - Medication adherence: what is the prescriber's responsibility?

PMID- 23002661
TI  - Postherpetic neuralgia: treatment strategies for pain control.

PMID- 23002662
TI  - Static renal scintigraphy with 99mTc-DMSA for the assessment of renal damage
      after therapy for acute lymphoblastic leukemia in children.
AB  - INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may adversely
      affect kidney function. The aim of the present study was to determine whether
      99mTc-DMSA static renal scintigraphy can be used to disclose kidney damage at the
      end of therapy for ALL in children. MATERIAL AND METHODS: The study group
      consisted of 48 ALL patients aged 6.6-22.9 years, with a mean time of continuous
      complete remission of 51 months. Static renal scintigraphy with 99mTc-DMSA was
      performed in all patients. RESULTS: Minor scars in the renal cortex were
      diagnosed with scintigraphy in 6 (13%) patients. A significant correlation was
      found between renal scarring and a history of urinary tract infection.
      CONCLUSIONS: No clinically significant kidney damage was found after completion
      of treatment of ALL. Static renal scintigraphy may be a valuable noninvasive
      method for visualization of renal cortex pathology.

PMID- 23002663
TI  - [Some aspects of molecular bases of keloid formation].
AB  - Keloid scarring, also known as keloid disease, is a benign, locally aggressive
      fibroproliferative scar overgrowth that expands with involvement of adjacent
      healthy skin. The pathogenesis of keloid disease has not been fully elucidated.
      In recent years, many reports have been published that unequivocally reveal
      genetic predispositions to keloid formation. Basing on the available literature,
      the authors present the most recent research on some aspects of molecular bases
      of keloid scarring.

PMID- 23002664
TI  - [Latent chronic kidney disease in the material of the Department of Vascular
      Surgery, Pomeranian Medical University in Szczecin. An important clinical
      problem].
AB  - INTRODUCTION: The percentage of patients with diagnosed chronic renal failure is
      many times smaller than the percentage of the latent disease. The rate of
      cardiovascular complications in latent kidney disease is significantly higher.
      The aim of this work was to determine the percentage of patients with renal
      failure among patients with peripheral atherosclerosis treated at our Department
      and to study rate (GFR) below the influence of reduced glomerular filtration rate
      (GFR) below 60 mL/min/1.73 m2 on the risk of early complications after vascular
      surgery. MATERIAL AND METHODS: A retrospective analysis of 1096 patients was
      done. 652 patients were operated, 321 underwent endovascular procedures,
      including angiography, antiglobulin test (PTA), and fibrinolysis, and 123 were
      conservatively treated. There were no significant differences between these
      groups as regards biochemical parameters prior to treatment. RESULTS:
      Approximately 2% of patients presented with chronic renal failure at admission.
      However, GFR in more than 30% (370) of them was lower than 60 mL/min/1.73 m2. The
      incidence of myocardial infarction and pneumonia was more than three-fold greater
      in patients with reduced GFR (1.89 vs. 0.55, p = 0.042; 4.59 vs. 1.38, p =
      0.0017, respectively). The incidence of gastrointestinal bleeding increased more
      than 18 times (3.78 vs. 0.28, p = 0.00002) and the incidence of stroke increased
      six times (2.43 vs. 0.41, p = 0.0032) in these patients. CONCLUSIONS: Latent
      renal failure is present in more than one-third of patients treated for
      peripheral atherosclerosis. GFR below 60 mL/min/1.73 m2 is associated with a
      higher risk of cardiovascular complications and postoperative gastrointestinal
      bleeding. Glomerular filtration rate should be routinely calculated at admission
      to hospital.

PMID- 23002665
TI  - [Quality of life in patients with idiopathic scoliosis treated operatively with
      the Cotrel-Dubousset method].
AB  - INTRODUCTION: Idiopathic scoliosis is a pathology which affects the individual's
      functioning in the widely understood physical, psychic, and social aspects. The
      aim of this study was to assess the dynamics of indicators of the quality of life
      and to search for correlations between the subjectively reported quality of life,
      radiographic findings, and some sociodemographic parameters. MATERIAL AND
      METHODS: The study was done in two independent groups of patients treated
      operatively at the Department of Pediatric Orthopaedic Surgery, Pomeranian
      Medical University in Szczecin. One group comprised 35 patients who were examined
      12 months after surgery. The other group comprised 52 patients who were examined
      after at least two years from surgery. The study tools included a personal data
      questionnaire, a clinical assessment form, and the SRS-22 Scoliosis Research
      Society's standardized tool for the measurement of dependent variables. RESULTS:
      Physical activity was perceived as deteriorating in proportion to the time
      passing from surgery and this finding was highly statistically significant. Pain
      was greater after 2 or more years from surgery. Mental health deteriorated in
      proportion to the time from surgery. No statistically significant differences as
      to the body image and satisfaction with treatment scores were noted. CONCLUSIONS:
      1. Deterioration of physical activity, mental health, and greater pain was
      reported by patients with socioeconomic problems and patients living in villages
      and small towns. 2. No correlation between the general quality of life and the
      degree of scoliosis in the thoracic or lumbar segment of the spine was found.

PMID- 23002666
TI  - [Analysis of the clinical picture and serologic profile in patients with
      dermatomyositis and polymyositis coexisting with neoplastic disease].
AB  - INTRODUCTION: There is much evidence on associations of dermatomyositis (DM) and
      polymyositis (PM) with malignant neoplasms. The prevalence of malignancies in
      patients with DM/PM is estimated at 6 to 60%. This study was undertaken to
      analyze the clinical and serologic picture of DM and PM coexisting with
      neoplastic disease. MATERIAL AND METHODS: We studied 61 patients (37 with PM, 16
      with DM, and 8 with the overlap syndrome - OVS). Diagnostic imaging, endoscopy,
      electromyography, histopathology of skin and muscle biopsies, echocardiography,
      and biochemical tests were done in all patients. The profile of antinuclear
      antibodies (ANA), myositis-specific autoantibodies (MSA), and myositis-associated
      autoantibodies was determined as well. Correlations of neoplastic disease with
      clinical, laboratory, and serologic parameters in patients with DM or PM were
      studied with logistic regression analysis. RESULTS: Neoplastic disease was
      diagnosed in eight patients (five with DM, two with PM, and one with OVS).
      Neoplastic disease was the cause of death in five patients. The mean time from
      diagnosis of DM/PM to diagnosis of tumor was 2.44 +/- 2.5 years. The most
      frequent clinical symptoms in patients with coexisting neoplastic disease were:
      dysphagia (8), myalgia (8), fever (7), skin lesions (5), pruritus (4), joint
      pain/effusion (4), and resistance to treatment (4). ANA were detected in six
      patients. None of the patients with a neoplasm tested MSA-positive; other
      antibodies were found in some patients. Risk factors for neoplastic disease
      included anemia at the time of diagnosis (OR: 16.75; 95% CI: 1.81-154.60; p =
      0.013) and dysphagia (OR: 5.08; 95% CI: 1.23-243.90; p = 0.031). CONCLUSION:
      Dysphagia and anemia at onset of the disease in a patient with idiopathic
      inflammatory myopathy are symptoms which suggest the risk of a tumor.

PMID- 23002667
TI  - [Diagnostic difficulties in gastrocolic fistulas as a complication of surgical
      management of peptic ulcer: case report].
AB  - A gastrointestinal fistula is a late complication of peptic ulcer disease and
      forms when gastric resection is inadequate or vagotomy is incomplete or not
      performed. Such cases are extremely rare and are occasionally reported in the
      literature. We present a patient with a gastrocolic fistula which developed 7
      years after partial gastrectomy due to pyloric stenosis as a sequella of peptic
      ulcer. Nonspecific clinical symptoms and ambiguous radiographic findings delayed
      the diagnosis of gastrocolic fistula. The patient was operated; "en bloc"
      resection of the fistula with partial resection of the transverse colon and
      stomach supplemented with truncal vagotomy was done. The possible cause of
      recurrence of peptic ulcer in this patient was that vagotomy was not done during
      the first surgical intervention. Thus, the gastrocolic fistula became a late
      complication of the recurrence of peptic ulcer. Diagnostic difficulties in
      gastrocolic fistulas are presented and surgical management of this complication
      is discussed.

PMID- 23002668
TI  - [New methods in physiotherapy. The Halliwick concept as a form of rehabilitation
      in water].
AB  - The Halliwick concept is not only a method teaching swimming to disabled
      patients; it is a holistic approach to therapy in water. The concept encompasses
      all areas of human life and has an impact on the physical, mental, and social
      development. The disabled persons have an opportunity to move unassisted in water
      and to swim. The logical pattern of the 10-point program provides the basis for
      exercises in water. By mastering subsequent points the participant becomes
      independent and skilled to actively participate in the exercises.

PMID- 23002669
TI  - [Attitudes of adults towards homosexuality and knowledge of sexually transmitted
      diseases: part one].
AB  - INTRODUCTION: This doctoral dissertation is the first scientific article in
      Poland with an in-depth analysis of subjective attitudes of members of various
      social groups towards persons with a homosexual orientation. The dissertation
      includes definitions of terms related to homosexuality, as well as changing
      opinions on gays and lesbians over the centuries from antiquity till modern
      times. Special attention is devoted to the biological background of human and
      animal homosexuality. Opinions of various experts are presented and the fate of
      homosexuals throughout history is discussed together with examples of persecution
      on one side and growing tolerance on the other. The aim of this study was to (a)
      investigate the attitudes of adults representing various social groups towards
      homosexuality; (b) evaluate the knowledge of respondents concerning biological
      and social aspects of homosexuality; (c) determine the degree of tolerance and
      acceptance of gays and lesbians. MATERIAL AND METHODS: The study was done in 2255
      respondents - students of various university faculties, as well as in teachers,
      servicemen, and cadets of the Military Academy. The study tool was a 24-item
      anonymous questionnaire. RESULTS: 1. Knowledge of problems relating to
      homosexuality differed among various social groups. Knowledge was highest among
      students of cultural studies and teachers. 2. The level of tolerance and
      acceptance towards homosexuals continues to rise, particularly among students of
      the humanities. 3. The type and field of studies has an impact on the shaping of
      attitudes of students towards the homosexually-oriented population. The highest
      level of acceptance was found among students of cultural studies and philosophy.
      Students of the military academy and physical education revealed animosity and
      negative attitudes. 4. Biological factors - gender and environmental factors -
      parents' social class - have an impact on the shaping of attitudes towards
      homosexuality. Males and respondents of peasant descent do not accept
      homosexuality. More positive attitudes are evolving among respondents of worker
      descent, possibly because of their migration to cities.

PMID- 23002670
TI  - [Attitudes of adults towards homosexuality and knowledge of sexually transmitted
      diseases: part two].
AB  - INTRODUCTION: This article based on the doctoral thesis focuses on sexually
      transmitted diseases (STD), their etiopathogenesis, symptomatology, history, and
      classification depending on groups of pathogens. The aim of this work was to
      examine the actual knowledge on STD and principles of condom use in the context
      of STD, including HIV/AIDS. MATERIAL AND METHODS: The study was done in 2255
      respondents - students of various university faculties, as well as in teachers,
      servicemen, and cadets of the Military Academy. The study tool was a 24-item
      anonymous questionnaire. RESULTS: 1. Unsatisfactory level of sex and health
      education contributes to lack of knowledge about STD. Many respondents did not
      understand the difference between HIV and AIDS and even more had an extremely low
      level of knowledge about the main sexually transmitted diseases (only 63% of
      respondents heard about gonorrhea and 58% about syphilis). 2. More than 90% of
      respondents did now know about sexually transmitted diseases like genital warts,
      venereal ulcer, chlamydioses, pubic lice, trichomoniasis, viral hepatitis, and
      genital herpes. 85% knew nothing about mycoses. 3. The majority of respondents
      knew the principles of condom use (approximately 30% did not, more than 5% would
      place the condom over the penis and scrotum).

PMID- 23002671
TI  - [The effect of lead and cadmium on the lipid profile and psychosocial functioning
      of children with developmental disorders].
AB  - INTRODUCTION: Impulsiveness, hyperactivity, and attention deficit are the most
      frequent neurocognitive disorders of childhood. Leaving aside the putative role
      of environmental and nutritive factors, the etiology and pathogenesis of these
      disorders remains unknown. The aim of this study was to examine the relationship
      between the concentration of lead, cadmium, and polyunsaturated fatty acids, and
      functioning of the child with developmental disorders. MATERIAL AND METHODS: The
      study enrolled 78 children with behavioral disorders. The mean age of the
      children was eight years. Standardized tools were used: Manfred Cierpka Family
      Assessment Measures, Children's Health Questionnaire Parent Form-28, and ADHD
      Rating Scale-IV. Concentrations of lead and cadmium in venous blood, lipid
      profile, and the percentage of some omega-3 and omega-6 fatty acids in the
      erythrocyte membrane were measured. RESULTS: A correlation between higher levels
      of lead in blood of the child and impulsive and hyperactive behaviors at home was
      observed. Concentrations of cadmium correlated with increased incidence of
      attention deficit at school. Analysis of the health profile revealed that lead
      and cadmium correlate with some of the elements that make up the image of a
      properly functioning child. Reduced levels of AA and EPA positively correlated
      with the incidence of hyperactive and impulsive behaviors. Reduced levels of GLA
      impaired the acceptance of norms and values. Levels of EPA and DHA had an impact
      on the overall state of health of the child, as well as on physical activity and
      feeling of loneliness. CONCLUSIONS: 1. Developmental disorders at school and
      difficulties in functioning at home may be the consequence of dysfunctions caused
      by lead and cadmium. 2. Deficiencies of AA, GLA, DHA, and EPA fatty acids or a
      disorder of their metabolism affect the behavior of the child in the form of
      hyperactivity, impulsiveness, and attention deficit.

PMID- 23002672
TI  - [Principles and methods of rehabilitation of patients with occupational voice
      disorders].
AB  - During recent years, voice disorders continued to hold the first position on the
      list of occupational diseases in Poland. Teachers constitute the largest group of
      persons whose profession is associated with a strong vocal effort. In 2003, 1100
      new cases of voice disorders were diagnosed (approx. 25% of all occupational
      diseases), reflecting the poor health status of persons with a voice-dependent
      profession (Data of the Institute of Occupational Medicine in Lodz). Due to
      specific conditions of work in the education sector, voice emission deteriorates
      after several or more years as teacher. The situation differs in singers, who
      rarely suffer from voice disorders thanks to special properties of their voice
      organ, as well as to many years of training and perfecting of voice emission
      techniques.

PMID- 23002673
TI  - [Association of the polymorphism of MUC7 gene encoding the low-molecular-weight
      mucin MG2 with susceptibility to caries].
AB  - INTRODUCTION: The aim of this study was to search for an association of the
      polymorphism of MUC7 gene encoding the low-molecular-weight mucin MG2 with
      susceptibility to caries. MATERIAL AND METHODS: The study enrolled 158 students
      (age 20-21 years) of the first and second year at the Faculty of Dentistry of the
      Pomeranian Medical University in Szczecin. The group included 77% females and 23%
      males. The DMF index was used to assess dental status. Oral hygiene was examined
      with the Approximal Plaque Index (API). The condition ofgingiva was reflected by
      the Gingival Bleeding Index (GBI). Isolation of DNA for the analysis of SNP
      polymorphism of the MUC7 gene was carried out with the Sherlock AX kit. Genotypes
      of the MUC7 gene were identified with PCR-RLFP. CONCLUSIONS: Statistical analysis
      showed that the MUC7*6/*6 genotype increased the probability of dental caries.
      Moreover, the MUC7*6/*6 genotype correlated positively with oral hygiene,
      predisposing to a higher value of the oral hygiene index. The present study did
      not disclose an association between MUC7*5/*6 and MUC7*6/*6 genotypes and GBI.

PMID- 23002674
TI  - Experience and attitudes of paramedics with regard to first aid in dental
      avulsion.
AB  - INTRODUCTION: The objective of this study was to assess the experience and
      attitudes of paramedics with regard to first aid in dental avulsion. MATERIAL AND
      METHODS: An anonymous, voluntary, 11-item survey was conducted in three randomly
      selected emergency medical service (EMS) stations in the Province of Podlasie. We
      analyzed what the respondents know about procedures in dental avulsion. We were
      also interested in the impact of professional and personal experience on the
      ability to take proper action in the case of avulsed/injured teeth. The use of
      teeth protectors during intubation was another aspect of our study. Data were
      statistically analyzed with the chi2 test. RESULTS: The study revealed that
      paramedics in EMS stations are not trained to provide first aid in dental
      avulsion. Avulsed teeth were usually not taken from the scene of the accident. We
      also found that previous experience with dental avulsion did not necessarily help
      to undertake proper action. However, we found that more than 95% of the
      respondents would act properly when not on duty. Paramedics do not use any teeth
      protectors to avoid accidental tooth injuries during intubation. CONCLUSION: We
      found that paramedics in the Province of Podlasie, Poland, need specialist
      training courses introducing them to principles of first aid in dental avulsion.
      Ambulances should carry equipment for the transport of avulsed teeth.

PMID- 23002675
TI  - Ozone in dentistry: microbiological effects of gas action depending on the method
      and the time of application using the ozonytron device. Experimental study.
AB  - INTRODUCTION: Bactericidal, virucidal, and fungicidal activity of ozone is
      generally known and has been exploited for years in industry and medicine. Ozone
      therapy became an inherent element of the treatment of infection in such fields
      as surgery, dermatology, cosmetics, and dentistry. Ozone is a gas, so it
      penetrates very well even into such tissues and spaces that are not easily
      accessible. Thanks to the property of deep penetration and long ozone presence in
      tissues after treatment, a long-lasting bactericidal effect is achieved. The
      action of oxygen radicals is, however, not neutral for the human organism,
      therefore the use of an appropriate procedure and therapy algorithms is
      essential. MATERIAL AND METHODS: We decided to confirm the effect of
      antibacterial activity of ozone applied by means of the Ozonytron device (made by
      Biozonix) on model strains of Streptococcus salivarius, pneumonia, pyogenes, and
      agalactiae, Enterococcus faecalis, Staphylococcus aureus and epidermidis, using
      two application patterns developed by us. RESULTS: We found a statistically
      significant difference in the size of zones of inhibited bacterial growth on all
      media depending on the time of action of ozone. In the present paper, the
      bactericidal activity of ozone in relation to bacterial strains that are most
      frequently isolated from the oral cavity was confirmed. What is more, two models
      of application of the gas on the infected medium were compared. CONCLUSION:
      Research on the use of ozone in combatting bacteria typical for dental diseases
      has shown that the gas has an oxidizing effect on these bacteria and is
      bactericidal.

PMID- 23002676
TI  - [The condition of teeth and periodotium in the elderly from social care centers
      and family-run care homes in the province of West Pomerania].
AB  - BACKGROUND: The aim of this study was to determine the impact of the environment
      on the health status of teeth and periodontium in the elderly. MATERIAL AND
      METHODS: The study group consisted of 226 patients, including 106 residents of
      two Social Care Centers in Gryfice and 120 residents of family-run care homes in
      or near Szczecin. The age of participants ranged from 55 to 101 years. There were
      110 males and 116 females in the group. Clinical examination of teeth was
      performed during one visit under natural lighting conditions, using a mirror and
      a dental probe according to criteria of the World Health Organization.
      CONCLUSIONS: 1. The health status of teeth and periodontium was poor in patients
      older than 55 years in both groups and was worse among residents of Social Care
      Centers. 2. Residents of Social Care Centers had more missing teeth or requiring
      extraction than residents of family-run care homes.

PMID- 23002677
TI  - ACS Futures Committee takes a good, hard look at the year 2025.

PMID- 23002678
TI  - The Bulletin of the American College of Surgeons: keeping fellows informed for
      nearly 100 years.

PMID- 23002679
TI  - The near-death of a president, and the birth of a career: an interview with Dr.
      Napolitano.

PMID- 23002680
TI  - The ACS and the ABCs of how quality measures are established and implemented.

PMID- 23002681
TI  - Capt. Brad Cooper provides an update on Joining Forces initiative.

PMID- 23002682
TI  - Modifications to ordering and certifying rules for physicians.

PMID- 23002683
TI  - Governors' Committee on Physician Competency and Health.

PMID- 23002685
TI  - Flu vaccination standards set for ASCs and OBSs.

PMID- 23002684
TI  - Announcing the surgical standards manual project: a call for volunteers.

PMID- 23002686
TI  - [Pseudomonas folliculitis outbreaks associated with swimming pools or whirlpools
      in two guest-room sites in the northern region of Israel].
AB  - In summer 2010-2011 two outbreaks of Pseudomonas foliculitis occurred among
      bathers who used the swimming pools or whirlpools in two guest-room sites. The
      source of the infection was traced to the swimming pools or whirlpools, which had
      not been chlorinated and monitored routinely. Of 40 bathers, 25 (62.5%) developed
      Pseudomonas folliculitis 2-4 days after exposure. Typically the rash began as a
      pruritic erythematous papule on the buttocks, axilla, and extremities, with
      fever, adenopathy and otitis externa. In the culture of the pustules and
      bacterial examination grew Pseudomonas aeroginosa. Pseudomonas folliculitis was
      first described by McCausland and Cox in 1975. To the best of our knowledge, this
      is the first description of outbreaks in swimming pools or whirlpools in guest
      room sites in Israel. This article describes the epidemiological and
      environmental health investigation of the two outbreaks. With the rising
      popularity of swimming pools and whirlpools in guest-room sites, physicians in
      the community and the emergency rooms may encounter this disease. We urge their
      real time report to the public health offices, in charge of the epidemiological
      inquires, aiming to prevent the occurrence of new cases or improper treatment of
      similar cases.

PMID- 23002687
TI  - [Multiple chronic conditions and morbidity burden: challenges and considerations
      for an organizational strategy].
AB  - Technological advances combined with the aging of the population bring about an
      increasingly growing number of patients with chronic conditions and multi
      morbidity. Multi-morbidity, the co-occurrence of chronic and/or non-chronic
      conditions in an individual, is the norm among elderly patients, and is becoming
      increasingly common among younger adults. The Israeli health system, like other
      systems worldwide, is faced with the challenges posed by the increase in complex
      multi-morbidity, in an era of growing fiscal constraints, a situation that can
      induce financial and organizational crises. To effectively cope with such
      circumstances, a paradigm shift is needed. Health systems need to focus on
      overall morbidity burden and multi-morbidity (rather than the prevailing one
      disease at a time approach) and on better care integration. The Israeli health
      system entails many of the essential elements for addressing the challenges of
      integrated care, including universal health coverage and advanced health
      information technology systems. Yet, like other health systems, there is a need
      for care management support mechanisms that are more effectively tailored to meet
      the needs of the highly multimorbid patients. This review outlines the
      organizational approach required to better align care for the main customers of
      health care in the 21st century: patients with multi-morbidity. We focus on four
      domains: assessment of morbidity burden according to measures that account for
      the interaction and synergism amongst conditions; integration across the care
      continuum; enhancement of primary care and self-management support approaches;
      and provision of uniquely tailored care management solutions for the highest risk
      multi-morbid patients.

PMID- 23002688
TI  - [Arrhythmic storm in a patient with Brugada syndrome--an unusual case].
AB  - Brugada syndrome is characterized by episodes of near sudden death or syncope.
      The heart is normal on physical, angiographic and echocardiographic examination.
      The characteristic ECG abnormalities consist of ST-segment elevation in leads V1
      V3 and pseudo right bundle branch block. The ECG changes can be transient,
      causing the diagnosis to be missed. Provocative testing with Flecainide or other
      sodium channel blocking drugs can be used to unmask the ECG abnormalities. This
      is a case study of a young male who had been diagnosed as suffering from Brugada
      syndrome and had a defibrillator implanted five years ago. This time the patient
      was admitted because of syncope and documented an arrhythmic storm (seven
      episodes of ventricular fibrillation, treated with the implanted defibrillator).
      The episode occurred following extreme anger and an "exciting event", evoking
      sympathetic activity. The issue of a different form of autonomic modulation:
      involving sodium channels' activity in the heart (sympathetic rather than vagal)
      is raised.

PMID- 23002689
TI  - [Ectopic pregnancy as a presenting symptom for lung cancer].
AB  - This article describes a rare presentation of squamous cell carcinoma of the
      lung, mimicking an ectopic pregnancy secreting beta-hCG protein in a 47 year old
      female smoker, who was treated with Methotrexate and subsequently curettage,
      tubectomy and right ovariectomy, because of suspected hydatidiform mole. This
      document presents a rare and chaotic case of lung cancer and reviews the
      differential diagnosis of an increased level of the beta-hCG marker and the
      therapeutic approach to these cases.

PMID- 23002690
TI  - [Apnea after general anesthesia for revision of uterus in parturient with K
      variant of the butyrylcholinesterase enzyme (BChE)].
AB  - A 30 years old parturient was admitted to the operating theatre for revision of
      uterus after spontaneous labor because of hemorrhage. She underwent general
      anesthesia induced by rapid sequence induction (RSI) technique. Apnea for 45
      minutes was observed after succinylcholine administration. Biochemistry
      laboratory tests from the operation day showed very low butyrylcholinesterase
      activity, and a repeated test after one month showed normal enzyme activity and
      inhibitors within the normal range. Genetic tests revealed heterozygosity for the
      K variant of BChE. This may explain the increased sensitivity to succinylcholine
      during pregnancy.

PMID- 23002691
TI  - [Etiology of severe pulmonary hypertension--possible role of metabolic syndrome].
AB  - BACKGROUND: In clinical practice the association between obesity and pulmonary
      hypertension (PH) is not rare. AIM: The aim of this study was to examine the
      prevalence of obesity and metabolic syndrome in patients with severe PH,
      especially cases without significant cardiac, pulmonary or vascular causes.
      METHODS: We retrospectively anaLyzed the records of 91 patients with severe PH in
      order to establish its causes. RESULTS: A total of 64% of the patients were
      women. The women were older than the men, 76.5 years vs 74.0. The BMI of the
      women was higher than the men, 37.0 vs 30.07. The most common causes of severe PH
      seen in an internal medicine ward are: severe heart failure (45.1%), chronic lung
      disease (16.5%) or a combination of both (12.1%). Overall, 11% of our study
      patients were morbidly obese without significant cardiac, pulmonary or vascular
      causes of PH. This group was characterized by high incidence of diabetes
      meLLitus, arterial hypertension, hyperlipidemia, atrial fibrillation and left
      ventricular (LV) diastolic dysfunction. CONCLUSION: Our results point to a
      possible association between metabolic syndrome and PH.

PMID- 23002692
TI  - [Surgical site infections: what about the children?].
AB  - Surgical site infections (SSIs) are uniformly defined for adults and children as
      infections that develop within 30 days after an operation and are classified as
      being either incisional or organ/space in the operated area. SSI rates among
      children are similar to adults, but are higher among neonates. SSIs represent a
      significant burden in terms of patient morbidity and mortality, length of
      hospitalization and cost to the health services. The difficulty in treatment and
      prevention of SSIs usually results from the variety of pathogens causing the
      infection. There are a multitude of risk factors influencing the development of
      SSIs that may be related to patient characteristics, such as younger age, and/or
      the surgical procedure, such as duration of surgery, wound class, and surgical
      technique. The prognostic scores which, to the best of our knowledge, have been
      developed and validated for adults, are yet to be adopted for children.
      Prevention of SSIs requires addressing the causes at each phase of patient
      treatment, uniformly for both adults and children. Guidelines for the prevention
      of SSIs have been developed; however, they are not specifically related to the
      pediatric patients and are not fully supported by evidence. For instance,
      management of prophylactic antibiotics is a standard for adults, but there is no
      clear agreement for children, and use of antibiotic prophylactics varies between
      medical centers. In summary, a systematic registry of SSIs among children in
      Israel is required along side of rigorous investigation of the risk factors and
      prevention program development.

PMID- 23002693
TI  - [Hypersensitivity reaction to radio contrast media: diagnosis, prevention and
      treatment].
AB  - More than 70 million radiographic examinations with radio contrast media are
      performed worldwide each year. The incidence of adverse reactions to radio
      contrast media is 5-13%. Adverse reactions include hypersensitivity reactions,
      chemotoxic reactions and renal toxicity. Hypersensitivity reactions to radio
      contrast media range from mild pruritus to life-threatening emergency. The
      differential diagnosis between hypersensitivity reaction to radio contrast media
      and chemotoxic reaction is challenging. The incidence of chemotoxic reactions is
      mainly affected by the chemical structure of the radio contrast media and the
      rate of infusion. The incidence of hypersensitivity radio contrast media reaction
      is affected by age and by the presence of asthma and other atopic diseases. The
      diagnosis of hypersensitivity reaction to radio contrast media is based on
      clinical manifestations. The additional value of laboratory tests is limited and
      questionable. In case of hypersensitivity radio contrast reaction, the infusion
      should be stopped immediately, airways should be protected and fluids, oxygen and
      drugs should be given. Prophylactic treatment before its administration may
      prevent hypersensitivity reactions to radio contrast media.

PMID- 23002694
TI  - [Anti mullerian hormone (AMH)--is it a new reliable marker of the ovarian
      reserve? Its role in predicting the ovarian response in assisted reproductive
      technology (ART)].
AB  - Anti-Mullerian hormone (AMH) is predominantly known for its important role in the
      differentiation of the male and female sexual system during the early embryonic
      period. Recently, many animal and human researches have been studying the role of
      the AMH in the postnatal ovarian function. In the female, AMH is produced by the
      granulosa cells of early developing follicles. It plays a major role in the
      folliculogenesis and seems to be able to inhibit the initiation of the growth of
      primordial follicles and FSH-induced follicles. As AMH is expressed throughout
      the folliculogenesis, from the primary follicular stage to the antral stage, the
      serum levels of AMH may represent both the quantity and the quality of ovarian
      follicles. Thus, the AMH levels may be useful as a new potential marker of the
      ovarian reserve. As compared to other ovarian reserve tests, the AMH has unique
      characteristics which make it a favorable marker. The measurement of AMH levels
      may be useful in the prediction of poor response and cycle cancellation as well
      as hyper-response and the ovarian hyperstimulation syndrome in assisted
      reproductive technology (ART). We assume that the measurement of AMH Levels may
      play a role in the individualization of treatment strategies among patients who
      are treated by ART. However, the AMH cannot predict the qualitative ovarian
      response in ART. In men, the AMH was not found to have satisfactory clinical
      utility as a single marker of spermatogenesis.

PMID- 23002696
TI  - [Bergen-Belsen liberation 15th April 1945--personal and professional
      reflections].
AB  - The Holocaust is presently part of the universal human identity in the 21st
      century, as well as a component of Jewish and Israeli identity. Contemplating the
      role of medicine in the Holocaust is crucial for health professionals' identity
      formation. This paper narrates the story of the Bergen-Belsen concentration camp,
      the events preceding its liberation and the months that followed in universal,
      Jewish, medical and personal dimensions. A British book (After Daybreak by
      S.Shepard, Shocken Books, 2005) addresses the Bergen-Belsen Liberation on 15.4.45
      and focuses on the medical relief operation mounted by the British. It tells the
      story, among others, of 96 volunteer medical students flown in from London to
      assist in the survivors' care. I have also heard the tales of Bergen-Belsen in
      those days from my late father who was there and was fortunately Liberated by the
      same British soldiers. My mother too stayed in Bergen-Belsen and left two months
      prior to liberation. By the end of May 1945 the British soldiers had left, the
      camp was transformed into a refugee camp, and it became a transit camp for
      preparation for Aliya and immigration. In 1948 my mother's younger sisters spent
      time there on their way to joining a kibbutz in Palestine. This is how I found
      myself caught in the duality of seeing, in my mind's eye, the picture portrayed
      by the book, the gaze of the camp's liberators and healers, as well as imagining
      myself in the shoes of my family members in the same place and time. This article
      conveys the dual gaze: the medicaL, that the health professionals present on the
      one hand, and the personal outlook--on the other hand.

PMID- 23002695
TI  - [Pharmacotherapy for conduct disorder in children and adolescents].
AB  - RATIONALE: Conduct disorder (CD) is a common disorder which is typified by a
      variety of behavioral problems and aggression. Treating CD is a challenge in the
      field of child and adolescent psychiatry. The use of drugs for this indication is
      broad despite the lack of systematic knowledge on this subject. OBJECTIVES: This
      paper aims to review research data available on the efficacy of the different
      medication classes and agents for CD and to specify the considerations that
      should be taken accordingly. MATERIALS AND METHODS: Trials on the pharmacotherapy
      of CD in children and adolescents are reviewed from the PubMed database (dated
      from 1980 until today). RESULTS: Trials of antipsychotics, lithium, anti
      epileptics, stimulants, alfa-2 agonists and beta-blockers were found. The use of
      typical antipsychotics is accompanied by major side-effects. Research on
      risperidone, the most investigated agent, shows it to be effective. Limited
      research with positive results is also available on quetiapine, olanzapine and
      aripiprazole. Trials of lithium yield contradictory results. Few trials with
      valproate suggest it to be effective for this indication. There is evidence
      showing the efficacy of stimulants but substance abuse is a potential risk in
      this population. The results for other agents are very few. CONCLUSIONS: There
      are few well controlled studies of the pharmacotherapy of conduct disorder in
      children and adolescents. The most proven efficacy is for the atypical
      antipsychotics. Valproate or lithium may be possible second or third
      alternatives, based on some supporting evidence. When Attention
      Deficit/Hyperactivity Disorder is diagnosed, stimulant use should be considered.
      Given the adverse effects profile of these agents on the one hand, and the
      developmental risks of avoiding medication on the other hand, a risk-benefit
      analysis should be conducted for each patient and adverse effects should be
      monitored carefully. More research is needed to broaden and deepen the knowledge
      on this subject.

PMID- 23002697
TI  - Grafting control of mainstay terpyridine self-assembled monolayers for the
      preparation of planar silicon surfaces with variable catalytic loadings.
AB  - Monolayers of terpyridine-derivatized silanes were self-assembled, with
      accurately controlled grafting densities, on single-crystal silicon surfaces.
      Complexation of the resulting terpyridine monolayers with Pd(OAc)(2) afforded a
      series of catalytic surfaces covering a full range of Pd loadings (0.14-0.85
      nmol.cm(-2)) in the aim to explore their impact on catalysis methodically. X-ray
      reflectivity (XRR), X-ray photoelectron spectroscopy (XPS), and inductively
      coupled plasma mass spectrometry (ICP-MS) were combined to afford a precise
      picture of the grafting density, chemical composition, and catalyst loadings of
      the surfaces investigated here. We report that the control of the terpyridine
      density and thus the control of catalytic loadings can be achieved through a fine
      modification of silanization concentrations, which affords surfaces with tunable
      catalytic activity.

PMID- 23002698
TI  - Cannabis use vulnerability among socially anxious users: cannabis craving during
      a social interaction.
AB  - Socially anxious individuals appear especially vulnerable to cannabis-related
      problems. However, the nature of the social anxiety-cannabis relation remains
      unclear. The present study examined the timing and specificity of cannabis
      craving in response to a social anxiety induction task among 82 (71% female)
      cannabis users randomly assigned to either a social interaction or reading task.
      Participants completed ratings of substance (cannabis, alcohol, cigarette)
      craving at baseline (prior to being informed of task assignment), before, during,
      and after task. The Time * Condition interaction was significant such that
      cannabis craving increased from before to during the task among participants in
      the social interaction condition, but not among those in the reading condition.
      This effect was specific to cannabis craving and was not observed for craving for
      alcohol or cigarettes. Data suggest that increases in state social anxiety may
      play a role in cannabis use behaviors.

PMID- 23002700
TI  - Editorial: the biopsychosocial model.

PMID- 23002699
TI  - Acute tubular necrosis and renal failure in patients with glomerular disease.
AB  - Renal failure is common in patients with glomerular disease. Although renal
      failure may result from the glomerular lesion itself, it is also observed in
      patients with minimal glomerular alterations. Degenerative changes and necrosis
      of the tubular epithelium are common findings in kidney biopsies from these
      patients. The aim of this work is to examine the association between acute
      tubular necrosis (ATN) and renal failure in patients with glomerulopathy and to
      estimate the relationship between the degree of ATN and renal failure in these
      patients. Data on age, sex, presence of nephrotic syndrome, and renal failure
      were recorded for 149 patients, who underwent a renal biopsy for the diagnosis of
      glomerulopathy. The biopsies were reviewed, and ATN, when present, was classified
      as one of four grades depending on its intensity. The mean age of the patients
      was 21 +/- 16 years. Eighty patients (54%) were male, 43 (42%) had renal failure,
      104 (72%) had nephrotic syndrome, and 66 (45%) had minimal change disease or
      focal segmental glomerulosclerosis. ATN was present in 115 (77%) patients. The
      frequency of renal failure was directly correlated with the intensity of ATN
      [odds ratio (OR) of 26.0 for patients with grade 2 lesions and OR of 45.5 for
      patients with grade 3 lesions]. ATN is a common finding in the biopsies of
      patients with glomerulopathy. The severity of ATN is directly associated with the
      frequency of renal failure in these patients.

PMID- 23002701
TI  - The need for a new medical model: a challenge for biomedicine.

PMID- 23002702
TI  - The effects of intimate partner violence on women and child survivors: an
      attachment perspective.
AB  - Approximately 25% of women in the United States report having experienced
      intimate partner violence (IPV) in an adult relationship with a male partner. For
      affected women, IPV has been shown to increase the risk of psychopathology such
      as depression, anxiety, and symptoms of posttraumatic stress. Further, studies
      suggest that the risk of IPV (victimization or perpetration) may be carried
      intergenerationally, and children exposed to IPV are at a greater risk of both
      attachment insecurity and internalizing/externalizing problems. The authors
      employ an attachment perspective to describe how insecure/non-balanced working
      models of the relational self and others may be evoked by, elicit, or exacerbate
      maladaptive outcomes following experiences of IPV for mothers and their children.
      This article draws on both rich theory and empirical evidence in a discussion of
      attachment patterns in violent relationships, psychopathological outcomes for
      exposed women, disruptions in the caregiving relationship that may confer risk to
      children of exposed mothers, and the biological, social, and attachment risk
      factors for children exposed to IPV. A clinical case example is presented and
      discussed in the context of attachment theory.

PMID- 23002703
TI  - Countertransference in the general hospital setting: implications for clinical
      supervision.
AB  - Psychiatry residents completing their consultation-liaison (CL) rotations are
      implicitly expected to recognize and consider countertransference reactions when
      offering clinical recommendations. Residents often lack formal guidance in this
      role, as there exists limited examination of clinical scenarios from a
      psychodynamic perspective. The authors present a historical review of the
      literature on countertransference with the medically ill and describe a clinical
      vignette illustrating the vicissitudes of liaison work. The case involves a
      psychotic patient with mental retardation and acute renal failure. Through
      refusal of care and a tumultuous clinical course, this patient elicited various
      countertransferential reactions from the primary care and CL teams, in turn
      adversely impacting treatment. The case illustrates how clinicians' failure to
      collaborate led to hospital administrators having to take on the liaison role.
      (1) A review of literature corroborates the importance of CL psychiatrists'
      assistance in the management of countertransference. At the same time, it is
      notable for a paucity of guidance in teaching these skills to psychiatry
      trainees. The psychiatry resident-in-training faces challenges and shortcomings
      in the management of countertransference. Formal training in this aspect of
      psychiatric consultation is lacking, as evidenced by extant publications. The
      authors propose future directions for research and teaching, with emphasis on
      clarifying the liaison component of CL psychiatry and advocating for
      establishment of psychodynamic psychotherapy training guidelines in the general
      hospital setting.

PMID- 23002704
TI  - The challenge of treating (and supervising) patients with borderline pathology in
      a residents' clinic.
AB  - Outpatients with borderline personality disorder (BPD) comprise up to 20% of
      psychiatry clinics, to which they are usually referred for treatment, not of
      their Axis II pathology but for comorbid Axis I conditions. The complex and
      intense transference and countertransference dynamics that patients with even
      "secondary" BPD evoke in psychotherapy treatments require careful handling and
      supervision. Cases can quickly lose focus, with resultant morbidity for both
      patient and treater alike. Little literature exists to guide supervision of
      psychiatry trainees treating outpatients with BPD and Axis I illness. We describe
      a case of a young woman with BPD with a comorbid major depressive episode (MDE)
      who was treated by a third-year psychiatry resident with a mixture of supportive
      and dynamic psychotherapy and medication management. The treatment rapidly became
      chaotic, with escalating levels of patient acting out and resident
      dissatisfaction. We outline suggestions for supervision of resident treatment of
      patients with comorbid or primary BPD, including importance of careful intake
      assessment and treatment formulation, the establishment of a clear-cut frame
      and/or treatment contract, and the need for contextualizing expectable
      transference and countertransference reactions. Last, we discuss the pros and
      cons of mixing psychotherapy techniques within the same treatment.

PMID- 23002705
TI  - The cost of chronic stress in childhood: understanding and applying the concept
      of allostatic load.
AB  - This article explores the concept of allostatic load and its utility as an
      integrative framework for thinking about the impact of chronic stress on children
      and adolescents. Allostatic load refers to the failure or exhaustion of normal
      physiologic processes that occurs in response to severe, frequent, or chronic
      stressors. This persistent physiologic dysregulation may lead to secondary health
      problems such as immunosuppression, obesity, atherosclerosis, and hypertension.
      Allostatic load can be measured and followed as a composite index of a group of
      physiologic parameters which fall outside of a normal range. Although research
      regarding allostatic load in children is limited, this article explores relevant
      studies and identifies ways in which the concept of allostatic load can be used
      to broaden approaches to assessment, case formulation, and treatment in children.
      The concept of allostatic load may be of particular interest to psychodynamic
      psychiatrists in recognizing the ways in which chronic stress and adverse
      childhood experiences lead not only to negative psychological sequelae but also
      to long-term health consequences including the possibility of premature death. It
      underscores the importance of monitoring patients' physical as well as
      psychological health and thinking about the complex interrelations between the
      two.

PMID- 23002706
TI  - Toward a definition of "hypersexuality" in children and adolescents.
AB  - Recent psychiatric literature has used the term "hypersexuality" to denote
      pathologically increased sexual behavior in children and adolescents. Various
      patterns of increased sexuality have been described in youth, including sexuality
      that is excessive, developmentally precocious, compulsive, aggressive, or
      otherwise socially inappropriate. Such "hypersexual" behavior in children and
      adolescents is associated with a variety of factors. Social factors include
      sexual abuse, physical abuse, life stress, and impaired family relationships.
      Psychiatric factors include emotional and behavioral problems in general,
      posttraumatic stress disorder and dissociative symptoms in particular, and
      possibly bipolar disorder. Despite the importance of increased sexual behavior in
      youth as a possible sign of these problems, there is currently no uniform
      definition in psychiatric literature of the term "hypersexuality" applied to
      children and adolescents. The usefulness of this term depends upon the degree to
      which it can be defined, measured, and distinguished from non-pathological
      juvenile sexual behavior. Research instruments are described that may be useful
      in measuring levels of sexual behavior in children and adolescents. Elements of a
      definition of juvenile hypersexuality are proposed based upon current knowledge
      about children and adolescents' sexuality in both normal development and a
      variety of conditions in which it is increased. Care is warranted in
      distinguishing between normal and abnormal sexual behavior in youth because of
      the variety of factors that can affect its measurement.

PMID- 23002707
TI  - Psychotherapy and pharmacotherapy: a contemporary perspective.
AB  - A contemporary perspective on psychotherapy and pharmacotherapy views both
      treatments as somatic in nature. Abandoning Cartesian dualism frees the clinician
      to consider therapeutic options based on the best available evidence rather than
      falsely dichotomizing approaches as biological or psychological. Evidence-based
      medicine is a helpful though limited paradigm upon which to base treatment
      decisions. Instead, clinicians should strive for an evidence-informed approach
      that is patient centered. This approach is illustrated in relation to depressive
      illness where moderators of outcome are examined (illness severity, history of
      trauma, personality disorders, patient preference) that will influence clinical
      recommendations on combining treatment. Psychotherapy is increasingly proving to
      be a valuable therapeutic modality across the severity spectrum, a finding at
      odds with current treatment practices.

PMID- 23002708
TI  - Evidence base for the molecular underpinnings of psychodynamic psychotherapy.

PMID- 23002710
TI  - Optogenetic investigation of neuropsychiatric diseases.
AB  - Optogenetic technology, also known as optogenetics, is a novel multidisciplinary
      field in biotechnology that integrates genetic engineering, electrophysiology,
      and optical and electronic engineering. This recently developed technology has
      evolved rapidly and generated considerable excitement in neuroscience research.
      This technology successfully solves the severe problem of achieving both high
      temporal and spatial precision within intact neural tissues of animals that
      electrical stimulation and pharmacological methods cannot achieve. It allows
      neurons to express light-sensitive genes that enable the identification,
      dissection, and manipulation of specific neural populations and their connections
      in the tissues and organs of awake animals with unprecedented spatial and
      temporal precision. Light-sensitive genes chiefly including the genetically
      targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR)
      cause intracellular ion flow during optical illumination. Subsequently, the
      neurons undergo a series of changes resulting from membrane depolarization or
      hyperpolarization. To date, there are many published research articles and
      reviews that describe this new technology; however, few of the reports concern
      its application to neuropsychiatric diseases. In this review, we summarize the
      most recent optogenetic research in these diseases, including Parkinson's disease
      (PD), epilepsy, schizophrenia, anxiety, fear, reward behaviors, and sleep
      disorders. We propose that novel optogenetics technology creates excellent
      opportunities for innovative treatment strategies of neuropsychiatric diseases.

PMID- 23002711
TI  - Ambulatory blood pressure monitoring: killing the elephant to get its hair? No
      more, please!

PMID- 23002712
TI  - Direct stereospecific amination of alkyl and aryl pinacol boronates.
AB  - The direct amination of alkyl and aryl pinacol boronates is accomplished with
      lithiated methoxyamine. This reaction directly provides aliphatic and aromatic
      amines, stereospecifically, and without preactivation of the boronate substrate.

PMID- 23002713
TI  - Monitoring of a simulated CO(2) leakage in a shallow aquifer using stable carbon
      isotopes.
AB  - Artificial carbon dioxide leakage into a shallow aquifer was monitored using
      stable carbon isotope measurements at a field site near the town of Wittstock,
      Brandenburg, Germany. Approximately 400 000 L of CO(2) were injected into a
      shallow aquifer at 18 m depth over 10 days. The (13)C/ (12)C ratios of the CO(2)
      were measured in both groundwater and soil gas samples to monitor the
      distribution of the injected CO(2) plume and to evaluate the feasibility and
      reliability of this approach to detect potential CO(2) leakage, for example from
      carbon capture and storage (CCS) sites. The isotopic composition of the injected
      CO(2) (delta(13)C -30.5 0/00) was differentiable from the background CO(2)
      (delta(13)C -21.9 0/00) and the artificial CO(2) plume was monitored over a
      period spanning more than 204 days. The results demonstrate that this stable
      isotope monitoring approach can be used to identify CO(2) sources and detect
      potential CO(2) migration from CCS sites into overlying shallow aquifers or even
      into the upper subsurface. A significant difference between the isotope ratios of
      the natural background and the injected CO(2) is required for this monitoring
      approach to be effective.

PMID- 23002714
TI  - Mobility stress test approach to predicting frailty, disability, and mortality in
      high-functioning older adults.
AB  - OBJECTIVES: To examine the validity of the Walking While Talking Test (WWT), a
      mobility stress test, to predict frailty, disability, and death in high
      functioning older adults. DESIGN: Prospective cohort study. SETTING: Community
      sample. PARTICIPANTS: Six hundred thirty-one community-residing adults aged 70
      and older participating in the Einstein Aging Study (mean follow-up 32 months).
      High-functioning status at baseline was defined as absence of disability and
      dementia and normal walking speeds. MEASUREMENTS: Hazard ratios (HRs) for
      frailty, disability, and all-cause mortality. Frailty was defined as presence of
      three out of the following five attributes: weight loss, weakness, exhaustion,
      low physical activity, and slow gait. The predictive validity of the WWT was also
      compared with that of the Short Physical Performance Battery (SPPB) for study
      outcomes. RESULTS: Two hundred eighteen participants developed frailty, 88
      developed disability, and 49 died. Each 10-cm/s decrease in WWT speed was
      associated with greater risk of frailty (HR = 1.12, 95% confidence interval (CI)
      = 1.06-1.18), disability (HR = 1.13, 95% CI = 1.03-1.23), and mortality (HR =
      1.13, 95% CI = 1.01-1.27). Most associations remained robust even after
      accounting for potential confounders and gait speed. Comparisons of HRs and model
      fit suggest that the WWT may better predict frailty whereas SPPB may better
      predict disability. CONCLUSION: Mobility stress tests such as the WWT are robust
      predictors of risk of frailty, disability, and mortality in high-functioning
      older adults.

PMID- 23002715
TI  - Neovascularized myxoma-causing abnormal blood flow in the left atrium diagnosed
      by transesophageal echocardiography.
AB  - Myxomas are the most common primary cardiac tumor, and neovascularization of
      cardiac myxoma has been shown in previous case reports. However, it is seldom
      reported that abnormal blood flow spurted from a neovascularized myxoma into the
      cardiac chamber. In this unusual case report, we present a left atrial myxoma in
      a 44-year-old woman with atypical angina. Transesophageal echocardiography (TEE)
      revealed several small blood streams spurting from the surface of massively
      vascularized myxoma into the left atrium. Coronary angiography showed a feeding
      artery which arose from the right coronary artery and supplied the left atrial
      myxoma, with no evidence of coronary artery stenosis. This case demonstrated that
      TTE might be helpful for confirming the neovascularization of myxoma in the left
      atrium and finding the abnormal blood flow that spurts from the neovascularized
      myxoma. We speculate that the abnormal blood flow spurting from the
      neovascularized myxoma into the left atrium may have caused a coronary steal
      phenomenon thus resulting in myocardial ischemia.

PMID- 23002718
TI  - Prospective evaluation of a 5 * 4 Gy prescription for palliation of canine nasal
      tumors.
AB  - We evaluated the efficacy of palliative radiation therapy using 5 * 4 Gy given
      daily in 18 dogs with nasal tumors. Dogs with malignant nasal tumors were
      evaluated for response rate, response duration, and survival. Seventy-eight
      percent of the dogs achieved complete resolution of clinical signs, and 16.5% had
      partial resolution of their signs. Overall median response duration for all dogs
      was 178 days after one course of radiation therapy. Six dogs received a second
      course of therapy when their disease progressed using the same daily 5 * 4 Gy
      scheme, and all six responded for a median time of 129.5 days for an overall
      median survival time in these six dogs of 309 days. Based on these results, a
      radiation prescription of 5 * 4 Gy appears to be useful palliatively in dogs with
      a malignant nasal tumor.

PMID- 23002720
TI  - Oral xylose isomerase decreases breath hydrogen excretion and improves
      gastrointestinal symptoms in fructose malabsorption - a double-blind, placebo
      controlled study.
AB  - BACKGROUND: Incomplete resorption of fructose results in increased colonic
      hydrogen production and is a frequent cause of abdominal symptoms. The only
      treatment available is diet. AIM: To study whether orally administered xylose
      isomerase (XI), an enzyme that catalyses the reversible isomerisation of glucose
      and fructose, can decrease breath hydrogen excretion in patients with fructose
      malabsorption. METHODS: Patients received 25 g fructose in 100 mL water together
      with either placebo or XI capsules. Primary endpoint was the reduction in breath
      hydrogen excretion, as assessed by the area under the breath hydrogen curve over
      4 h (AUC). A secondary endpoint was the reduction in abdominal pain, bloating and
      nausea assessed on a visual analogue scale (VAS, range: 0-10). A P value <0.05
      was considered statistically significant. RESULTS: Sixty-five patients in whom
      fructose malabsorption had been diagnosed by positive breath hydrogen test within
      the previous year, were included in the study [15 males, 50 females; mean age
      43.3 (s.d. = 14.4), range: 21-73 years]. The median AUC was 885 ppm/240 min in
      the XI group compared to 2071 ppm/240 min in the placebo group (P = 0.00). Median
      scores for abdominal pain (0.7 vs. 1.3) and nausea (0.2 vs. 0.6), but not for
      bloating (P = 0.053), were significantly improved after XI (P = 0.009 and P =
      0.005) as compared with placebo. CONCLUSIONS: Oral administration of xylose
      isomerase significantly decreased breath hydrogen excretion after ingestion of a
      watery fructose solution. Nausea and abdominal pain were significantly improved
      by xylose isomerase.

PMID- 23002719
TI  - Trajectories of internalizing problems in war-affected Sierra Leonean youth:
      examining conflict and postconflict factors.
AB  - Three waves of data from a prospective longitudinal study in Sierra Leone were
      used to examine internalizing trajectories in 529 war-affected youth (ages 10-17
      at baseline; 25% female). Latent class growth analyses identified 4 trajectories:
      A large majority of youth maintained lower levels of internalizing problems
      (41.4%) or significantly improved over time (47.6%) despite very limited access
      to care, but smaller proportions continued to report severe difficulties 6 years
      postwar (4.5%) or their symptoms worsened (6.4%). Continued internalizing
      problems were associated with loss of a caregiver, family abuse and neglect, and
      community stigma. Despite the comparative resilience of most war-affected youth
      in the face of extreme adversity, there remains a compelling need for
      interventions that address family- and community-level stressors.

PMID- 23002722
TI  - Making good choices about publishing in the journal jungle.

PMID- 23002721
TI  - Railway-controller-perceived mental work load, cognitive failure and risky
      commuting.
AB  - This questionnaire study tests cognitive failures as a mediator of the potential
      influence of mental work demands and conscientiousness on risky commuting.
      Participants were 104 railway-controllers (19% female). Failure of memory,
      attention regulation and action execution were assessed with the Workplace
      Cognitive Failure (WCF) scale. Mental work demands were measured by the
      Instrument for Stress-Oriented Task Analysis (ISTA). A structural equation model
      testing WCF as the mediator of (1) the relationship between mental work demands
      and risky commuting (p < 0.05) and (2) the link between conscientiousness and
      risky commuting (p < 0.05) fitted well with empirical data. In railway
      controllers frequent interruptions, time pressure, and high concentration demands
      are likely to increase cognitive load and thereby boost WCF during work and also
      during commuting, thereby reducing commuting safety. The results underline the
      need for work redesign to improve commuting safety. PRACTITIONER SUMMARY:
      Commuting accidents occur frequently and at high cost. This study shows that
      mental work demands of railway staff are related to cognitive failure and risky
      commuting behaviour such as failing to give way and overlooking stop signs.
      Primary prevention of commuting accidents should include reduction of mental
      workload.

PMID- 23002723
TI  - Intermolecular pi-electron perturbations generate extrinsic visible contributions
      to eumelanin black chromophore in model polymers with interrupted interring
      conjugation.
AB  - The key structural factors underlying the unique black chromophore of eumelanin
      biopolymers have so far defied elucidation. Capitalizing on the ability of 1%
      polyvinylalcohol (PVA) to prevent pigment precipitation during melanogenesis in
      vitro, we have investigated the visible chromophore properties of soluble
      eumelanin-like polymers produced by biomimetic oxidation of 5,6-dihydroxyindole
      (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in 1% PVA-containing
      buffer at pH 7. Upon dilution DHI-eumelanin solutions exhibited almost linear
      visible absorbance changes, whereas DHICA-eumelanin displayed a remarkable
      deviation from linearity in simple buffer, but not in PVA-containing buffer. It
      is suggested that in DHICA polymers, exhibiting repeated interruptions of
      interring conjugation due to lack of planar conformations, the black chromophore
      is not due to an overlap of static entities defined intrinsically by the
      conjugation length across the carbon frame, but results largely from aggregation
      related intermolecular perturbations of the pi-electron systems which are
      extrinsic in character.

PMID- 23002725
TI  - Macroscopic quantum self-trapping in dynamical tunneling.
AB  - It is well known that increasing the nonlinearity due to repulsive atomic
      interactions in a double-well Bose-Einstein condensate suppresses quantum
      tunneling between the two sites. Here we find analogous behavior in the dynamical
      tunneling of a Bose-Einstein condensate between period-one resonances in a single
      driven potential well. For small nonlinearities we find unhindered tunneling
      between the resonances, but with an increasing period as compared to the
      noninteracting system. For nonlinearities above a critical value we generally
      observe that the tunneling shuts down. However, for certain regimes of modulation
      parameters we find that dynamical tunneling reemerges for large enough
      nonlinearities, an effect not present in spatial double-well tunneling. We
      develop a two-mode model in good agreement with full numerical simulations over a
      wide range of parameters, which allows the suppression of tunneling to be
      attributed to macroscopic quantum self-trapping.

PMID- 23002724
TI  - MU-Opioid receptor desensitization: homologous or heterologous?
AB  - There is considerable controversy over whether MU-opioid receptor (MOPr)
      desensitization is homologous or heterologous and over the mechanisms underlying
      such desensitization. In different cell types MOPr desensitization has been
      reported to involve receptor phosphorylation by various kinases, including G
      protein-coupled receptor kinases (GRKs), second messenger and other kinases as
      well as perturbation of the MOPr effector pathway by GRK sequestration of G
      protein betagamma subunits or ion channel modulation. Here we report that in
      brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (5-8
      weeks old) rapid MOPr desensitization induced by the high-efficacy opioid
      peptides methionine enkephalin and DAMGO was homologous and not heterologous to
      alpha(2)-adrenoceptors and somatostatin SST(2) receptors. Given that these
      receptors all couple through G proteins to the same set of G-protein inwardly
      rectifying (GIRK) channels it is unlikely therefore that in mature neurons MOPr
      desensitization involves G protein betagamma subunit sequestration or ion channel
      modulation. In contrast, in slices from immature animals (less than postnatal day
      20), MOPr desensitization was observed to be heterologous and could be downstream
      of the receptor. Heterologous MOPr desensitization was not dependent on protein
      kinase C or c-Jun N-terminal kinase activity, but the change from heterologous to
      homologous desensitization with age was correlated with a decrease in the
      expression levels of GRK2 in the LC and other brain regions. The observation that
      the mechanisms underlying MOPr desensitization change with neuronal development
      is important when extrapolating to the mature brain results obtained from
      experiments on expression systems, cell lines and immature neuronal preparations.

PMID- 23002726
TI  - Bosonic Josephson junction controlled by a single trapped ion.
AB  - We theoretically investigate the properties of a double-well bosonic Josephson
      junction coupled to a single trapped ion. We find that the coupling between the
      wells can be controlled by the internal state of the ion, which can be used for
      studying mesoscopic entanglement between the two systems and to measure their
      interaction with high precision. As a particular example we consider a single
      ^{87}Rb atom and a small Bose-Einstein condensate controlled by a single 171Yb+
      ion. We calculate interwell coupling rates reaching hundreds of Hz, while the
      state dependence amounts to tens of Hz for plausible values of the currently
      unknown s-wave scattering length between the atom and the ion. The analysis shows
      that it is possible to induce either the self-trapping or the tunneling regime,
      depending on the internal state of the ion. This enables the generation of large
      scale ion-atomic wave packet entanglement within current technology.

PMID- 23002727
TI  - Controlling fast transport of cold trapped ions.
AB  - We realize fast transport of ions in a segmented microstructured Paul trap. The
      ion is shuttled over a distance of more than 10(4) times its ground state wave
      function size during only five motional cycles of the trap (280 MUm in 3.6 MUs).
      Starting from a ground-state-cooled ion, we find an optimized transport such that
      the energy increase is as low as 0.10+/-0.01 motional quanta. In addition, we
      demonstrate that quantum information stored in a spin-motion entangled state is
      preserved throughout the transport. Shuttling operations are concatenated, as a
      proof-of-principle for the shuttling-based architecture to scalable ion trap
      quantum computing.

PMID- 23002728
TI  - Coherent diabatic ion transport and separation in a multizone trap array.
AB  - We investigate the dynamics of single and multiple ions during transport between
      and separation into spatially distinct locations in a multizone linear Paul trap.
      A single 9Be+ ion in a ~2 MHz harmonic well was transported 370 MUm in 8 MUs,
      corresponding to 16 periods of oscillation, with a gain of 0.1 motional quanta.
      Similar results were achieved for the transport of two ions. We also separated
      chains of up to 9 ions from one potential well to two distinct potential wells.
      With two ions this was accomplished in 55 MUs, with excitations of approximately
      two quanta for each ion. Fast transport and separation can significantly reduce
      the time overhead in certain architectures for scalable quantum information
      processing with trapped ions.

PMID- 23002729
TI  - Using separable Bell-diagonal states to distribute entanglement.
AB  - One of the many bizarre features of entanglement is that Alice, by sending a
      qubit to Bob in a separable state, can generate some entanglement between herself
      and Bob. This protocol is stripped down to the bare essentials to better
      elucidate the key properties of the initial resource state that enable this
      entanglement distribution. The necessary and sufficient conditions under which
      the correlations of a Bell-diagonal state serve as a useful resource are proven,
      giving upper and lower bounds on the entanglement that can be distributed when
      those conditions are met.

PMID- 23002730
TI  - Resource efficient source of multiphoton polarization entanglement.
AB  - Current photon entangling schemes require resources that grow with the photon
      number. We present a new approach that generates quantum entanglement between
      many photons, using only a single source of entangled photon pairs. The different
      spatial modes, one for each photon as required by other schemes, are replaced by
      different time slots of only two spatial modes. States of any number of photons
      are generated with the same setup, solving the scalability problem caused by the
      previous need for extra resources. Consequently, entangled photon states of
      larger numbers than before are practically realizable.

PMID- 23002731
TI  - Efficient measurement of quantum gate error by interleaved randomized
      benchmarking.
AB  - We describe a scalable experimental protocol for estimating the average error of
      individual quantum computational gates. This protocol consists of interleaving
      random Clifford gates between the gate of interest and provides an estimate as
      well as theoretical bounds for the average error of the gate under test, so long
      as the average noise variation over all Clifford gates is small. This technique
      takes into account both state preparation and measurement errors and is scalable
      in the number of qubits. We apply this protocol to a superconducting qubit system
      and find a bounded average error of 0.003 [0,0.016] for the single-qubit gates
      X(pi/2) and Y(pi/2). These bounded values provide better estimates of the average
      error than those extracted via quantum process tomography.

PMID- 23002732
TI  - Improved tests of local position invariance using 87Rb and 133Cs fountains.
AB  - We report tests of local position invariance based on measurements of the ratio
      of the ground state hyperfine frequencies of 133Cs and 87Rb in laser-cooled
      atomic fountain clocks. Measurements extending over 14 years set a stringent
      limit to a possible variation with time of this ratio: d ln(nu(Rb)/nu(Cs))/dt=(
      1.39+/-0.91)*10(-16) yr(-1). This improves by a factor of 7.7 over our previous
      report [H. Marion et al., Phys. Rev. Lett. 90, 150801 (2003)]. Our measurements
      also set the first limit to a fractional variation of the Rb/Cs frequency ratio
      with gravitational potential at the level of c(2)d ln(nu(Rb)/nu(Cs))/dU=(0.11+/
      1.04)*10(-6), providing a new stringent differential redshift test. The above
      limits equivalently apply to the fractional variation of the quantity alpha(
      0.49)(g(Rb)/g(Cs)), which involves the fine-structure constant alpha and the
      ratio of the nuclear g-factors of the two alkalis. The link with variations of
      the light quark mass is also presented together with a global analysis combining
      other available highly accurate clock comparisons.

PMID- 23002733
TI  - Minimagnetospheres above the lunar surface and the formation of lunar swirls.
AB  - In this paper we present in situ satellite data, theory, and laboratory
      validation that show how small-scale collisionless shocks and minimagnetospheres
      can form on the electron inertial scale length. The resulting retardation and
      deflection of the solar wind ions could be responsible for the unusual "lunar
      swirl" patterns seen on the surface of the Moon.

PMID- 23002734
TI  - Schwarzschild black holes can wear scalar wigs.
AB  - We study the evolution of a massive scalar field surrounding a Schwarzschild
      black hole and find configurations that can survive for arbitrarily long times,
      provided the black hole or the scalar field mass is small enough. In particular,
      both ultralight scalar field dark matter around supermassive black holes and
      axionlike scalar fields around primordial black holes can survive for
      cosmological times. Moreover, these results are quite generic in the sense that
      fairly arbitrary initial data evolve, at late times, as a combination of those
      long-lived configurations.

PMID- 23002735
TI  - Gravitational waves from color-magnetic "mountains" in neutron stars.
AB  - Neutron stars may harbor the true ground state of matter in the form of strange
      quark matter. If present, this type of matter is expected to be a color
      superconductor, a consequence of quark pairing with respect to the color and
      flavor degrees of freedom. The stellar magnetic field threading the quark core
      becomes a color-magnetic admixture and, in the event that superconductivity is of
      type II, leads to the formation of color-magnetic vortices. In this Letter, we
      show that the volume-averaged color-magnetic vortex tension force should
      naturally lead to a significant degree of nonaxisymmetry in systems such as radio
      pulsars. We show that gravitational radiation from such color-magnetic
      "mountains" in young pulsars, such as the Crab and Vela, could be observable by
      the future Einstein Telescope, thus, becoming a probe of paired quark matter in
      neutron stars. The detectability threshold can be pushed up toward the
      sensitivity level of Advanced LIGO if we invoke an interior magnetic field about
      a factor ten stronger than the surface polar field.

PMID- 23002736
TI  - Observing the dynamics of supermassive black hole binaries with pulsar timing
      arrays.
AB  - Pulsar timing arrays are a prime tool to study unexplored astrophysical regimes
      with gravitational waves. Here, we show that the detection of gravitational
      radiation from individually resolvable supermassive black hole binary systems can
      yield direct information about the masses and spins of the black holes, provided
      that the gravitational-wave-induced timing fluctuations both at the pulsar and at
      Earth are detected. This in turn provides a map of the nonlinear dynamics of the
      gravitational field and a new avenue to tackle open problems in astrophysics
      connected to the formation and evolution of supermassive black holes. We discuss
      the potential, the challenges, and the limitations of these observations.

PMID- 23002737
TI  - AdS/QCD holographic wave function for the rho meson and diffractive rho meson
      electroproduction.
AB  - We show that anti-de Sitter/quantum chromodynamics generates predictions for the
      rate of diffractive rho-meson electroproduction that are in agreement with data
      collected at the Hadron Electron Ring Accelerator electron-proton collider.

PMID- 23002738
TI  - Maximal R-symmetry violating amplitudes in type IIb superstring theory.
AB  - On-shell superspace techniques are used to quantify R-symmetry violation in type
      IIB superstring theory amplitudes in a flat background in 10 dimensions. This
      shows the existence of a particularly simple class of nonvanishing amplitudes in
      this theory, which violate R symmetry maximally. General properties of the class
      and some of its extensions are established that at string tree level are shown to
      determine the first three nontrivial effective field theory contributions to all
      multiplicity. This leads to a natural conjecture for the exact analytic part of
      the first two of these.

PMID- 23002741
TI  - Charm production in association with an electroweak gauge boson at the LHC.
AB  - The production of charm quark jets in association with electroweak gauge bosons
      at the LHC can be used as a tool to constrain quark parton distribution functions
      (PDFs). Motivated by recent measurements at the Tevatron and LHC, we calculate
      cross sections for W/Z+c, comparing these to W/Z+jet, for various PDF sets. The
      cross-section differences can be understood in terms of the different underlying
      PDFs, with the strange quark distribution being particularly important for W+c
      production. We suggest measurements of appropriately defined ratios and comment
      on how these measurements at the LHC can be used to extract information on the
      strange and charm content of the proton at high Q(2) scales.

PMID- 23002740
TI  - Observation of the etab(2S) Meson in Upsilon(2S)->gammaetab(2S), etab(2S)->
      hadrons and confirmation of the etab(1S) meson.
AB  - The data for 9.3 million Upsilon(2S) and 20.9 million Upsilon(1S) taken with the
      CLEO III detector have been used to study the radiative population of states
      identified by their decay into 26 different exclusive hadronic final states. In
      the Upsilon(2S) decays, an enhancement is observed at a ~5sigma level at a mass
      of 9974.6+/-2.3(stat)+/-2.1(syst) MeV. It is attributed to eta(b)(2S) and
      corresponds to the Upsilon(2S) hyperfine splitting of 48.7+/-2.3(stat)+/
      2.1(syst) MeV. In the Upsilon(1S) decays, the identification of eta(b)(1S) is
      confirmed at a ~3sigma level with M[eta(b)(1S)] in agreement with its known
      value.

PMID- 23002743
TI  - Probing the longitudinal momentum spread of the electron wave packet at the
      tunnel exit.
AB  - We present an ellipticity-resolved study of momentum distributions arising from
      strong-field ionization of helium. The influence of the ion potential on the
      departing electron is considered within a semiclassical model consisting of an
      initial tunneling step and subsequent classical propagation. We find that the
      momentum distribution can be explained by including the longitudinal momentum
      spread of the electron at the exit from the tunnel. Our combined experimental and
      theoretical study provides an estimate of this momentum spread.

PMID- 23002744
TI  - Controllable binding of polar molecules and metastability of one-dimensional
      gases with attractive dipole forces.
AB  - We explore one-dimensional samples of ultracold polar molecules with attractive
      dipole-dipole interactions and show the existence of a repulsive barrier caused
      by a strong quadrupole interaction between molecules. This barrier can stabilize
      a gas of ultracold KRb molecules and even lead to long-range wells supporting
      bound states between the molecules. The properties of these wells can be
      controlled by external electric fields, allowing the formation of long
      polymerlike chains of KRb and studies of quantum phase transitions by varying the
      effective interaction between molecules. We discuss the generalization of those
      results to other systems.

PMID- 23002742
TI  - Attosecond control of orbital parity mix interferences and the relative phase of
      even and odd harmonics in an attosecond pulse train.
AB  - We experimentally demonstrate that atomic orbital parity mix interferences can be
      temporally controlled on an attosecond time scale. Electron wave packets are
      formed by ionizing argon gas with a comb of odd and even high-order harmonics, in
      the presence of a weak infrared field. Consequently, a mix of energy-degenerate
      even and odd parity states is fed in the continuum by one- and two-photon
      transitions. These interfere, leading to an asymmetric electron emission along
      the polarization vector. The direction of the emission can be controlled by
      varying the time delay between the comb and infrared field pulses. We show that
      such asymmetric emission provides information on the relative phase of
      consecutive odd and even order harmonics in the attosecond pulse train.

PMID- 23002745
TI  - Observation of Raman optical activity by heterodyne-detected polarization
      resolved coherent anti-Stokes Raman scattering.
AB  - We report the first observation of Raman optical activity (ROA) by coherent anti
      Stokes Raman scattering. Thanks to the more freedom of polarization
      configurations in coherent anti-Stokes Raman scattering than in spontaneous Raman
      spectroscopy, the contrast ratio of the chiral signal to the achiral background
      has been improved markedly. For (-)-beta-pinene, it is 2 orders of magnitude
      better than that in the reported spontaneous ROA measurement. This is also the
      first measurement of ROA signal using a pulsed laser source.

PMID- 23002746
TI  - Metamaterials controlled with light.
AB  - We suggest and verify experimentally the concept of functional metamaterials
      whose properties are remotely controlled by illuminating the metamaterial with a
      pattern of visible light. In such metamaterials arbitrary gradients of the
      effective material parameters can be achieved simply by adjusting the profile of
      illumination. We fabricate such light-tunable microwave metamaterials and
      demonstrate their unique functionalities for reflection, shaping, and focusing of
      electromagnetic waves.

PMID- 23002747
TI  - Increasing quantum degeneracy by heating a superfluid.
AB  - We consider a uniform superfluid confined in two compartments connected by a
      superleak and initially held at equal temperatures. If one of the two
      compartments is heated, a fraction of the superfluid will flow through the
      superleak. We show that, under certain thermodynamic conditions, the atoms flow
      from the hotter to the colder compartment, contrary to what happens in the
      fountain effect observed in superfluid helium. This flow causes quantum
      degeneracy to increase in the colder compartment. In superfluid helium, this
      novel thermomechanical effect takes place in the phonon regime of very low
      temperatures. In dilute quantum gases, it occurs at all temperatures below T(c).
      The increase in quantum degeneracy reachable through the adiabatic displacement
      of the wall separating the two compartments is also discussed.

PMID- 23002748
TI  - Size-differentiated lateral migration of bubbles in Couette flow of two
      dimensional foam.
AB  - We report experiments on lateral migration of bubbles in a two-dimensional foam
      sheared in a narrow-gap Couette device. A larger bubble in an otherwise
      monodisperse bubble raft migrates toward the center of the gap as long as the
      bubble size ratio and the shear rate are each above a threshold. The migration
      speed is roughly two orders of magnitude higher than that of a single bubble, and
      increases with the shear rate and the size ratio. The bubble also deforms much
      more than an isolated one at the same shear rate. Modifying the Chan-Leal
      solution for the migration of a single submerged bubble or drop, we derive a
      formula that successfully predicts all the migration trajectories recorded in the
      experiment. The threshold for migration corresponds to the wall repulsion force
      overcoming the capillary force in the two-dimensional foam. The size
      differentiated bubble migration provides an explanation for previously observed
      size segregation in sheared three-dimensional polydisperse foams.

PMID- 23002749
TI  - Novel vortex generator and mode converter for electron beams.
AB  - A mode converter for electron vortex beams is described. Numerical simulations,
      confirmed by experiment, show that the converter transforms a vortex beam with a
      topological charge m=+/-1 into beams closely resembling Hermite-Gaussian HG(10)
      and HG(01) modes. The converter can be used as a mode discriminator or filter for
      electron vortex beams. Combining the converter with a phase plate turns a plane
      wave into modes with topological charge m=+/-1. This combination serves as a
      generator of electron vortex beams of high brilliance.

PMID- 23002750
TI  - Observation of strong oscillations of areal mass in an unsupported shock wave.
AB  - An experimental study of hydrodynamic perturbation evolution in a strong
      unsupported shock wave, which is immediately followed by an expansion wave, is
      reported. A planar solid plastic target rippled on the front side is irradiated
      with a 350-450 ps long laser pulse. The perturbation evolution in the target is
      observed using face-on monochromatic x-ray radiography during and for up to 4 ns
      after the laser pulse. The theoretically predicted large oscillations of the
      areal mass in the target are observed for the first time. Multiple phase
      reversals of the areal mass modulation are detected.

PMID- 23002751
TI  - Observation of the avalanche of runaway electrons in air in a strong electric
      field.
AB  - The generation of an avalanche of runaway electrons is demonstrated for the first
      time in a laboratory experiment. Two flows of runaway electrons are formed
      sequentially in an extended air discharge gap at the stage of delay of a pulsed
      breakdown. The first, picosecond, runaway electron flow is emitted in the cathode
      region where the field is enhanced. Being accelerated in the gap, this beam
      generates electrons due to impact ionization. These secondary electrons form a
      delayed avalanche of runaway electrons if the field is strong enough. The
      properties of the avalanche correspond to the existing notions about the runaway
      breakdown in air. The measured current of the avalanche exceeds up to an order
      the current of the initiating electron beam.

PMID- 23002752
TI  - Seed laser chirping for enhanced backward Raman amplification in plasmas.
AB  - Backward Raman compression in plasma enables pulse compression to intensities not
      available using material gratings. Mediating the compression with higher density
      plasma generally produces shorter and therefore more intense output pulses.
      However, very high density plasma, even if sufficiently tenuous to be transparent
      to the laser, also produces group velocity dispersion of the amplified pulse,
      deleteriously affecting the interaction. What is shown here is that, by chirping
      the seed pulse, the group velocity dispersion may in fact be used advantageously,
      achieving the maximum intensities over the shortest distances while minimizing
      unwanted effects.

PMID- 23002753
TI  - Ultracold fermionic Feshbach molecules of 23Na40K.
AB  - We report on the formation of ultracold weakly bound Feshbach molecules of
      23Na40K, the first fermionic molecule that is chemically stable in its absolute
      ground state. The lifetime of the nearly degenerate molecular gas exceeds 100 ms
      in the vicinity of the Feshbach resonance. The measured dependence of the
      molecular binding energy on the magnetic field demonstrates the open-channel
      character of the molecules over a wide field range and implies significant
      singlet admixture. This will enable efficient transfer into the singlet
      vibrational ground state, resulting in a stable molecular Fermi gas with strong
      dipolar interactions.

PMID- 23002754
TI  - Bose-Hubbard models with synthetic spin-orbit coupling: Mott insulators, spin
      textures, and superfluidity.
AB  - Motivated by the experimental realization of synthetic spin-orbit coupling for
      ultracold atoms, we investigate the phase diagram of the Bose-Hubbard model in a
      non-Abelian gauge field in two dimensions. Using a strong coupling expansion in
      the combined presence of spin-orbit coupling and tunable interactions, we find a
      variety of interesting magnetic Hamiltonians in the Mott insulator (MI), which
      support magnetic textures such as spin spirals and vortex and Skyrmion crystals.
      An inhomogeneous mean-field treatment shows that the superfluid (SF) phases
      inherit these exotic magnetic orders from the MI and display, in addition,
      unusual modulated current patterns. We present a slave-boson theory which gives
      insight into such intertwined spin-charge orders in the SF, and discuss
      signatures of these orders in Bragg scattering, in situ microscopy, and dynamic
      quench experiments.

PMID- 23002755
TI  - Exotic quantum spin models in spin-orbit-coupled Mott insulators.
AB  - We study cold atoms in an optical lattice with synthetic spin-orbit coupling in
      the Mott-insulator regime. We calculate the parameters of the corresponding tight
      binding model using Peierls substitution and "localized Wannier states method"
      and derive the low-energy spin Hamiltonian for bosons and fermions. The spin
      Hamiltonian is a combination of Heisenberg model, quantum compass model and
      Dzyaloshinskii-Moriya interactions and it has a rich classical phase diagram with
      collinear, spiral and vortex phases. We discuss the state of the art of
      experiments to realize and detect magnetic orderings in strongly correlated
      optical lattices.

PMID- 23002756
TI  - Localized phase structures growing out of quantum fluctuations in a quench of
      tunnel-coupled atomic condensates.
AB  - We investigate the relative phase between two weakly interacting 1D condensates
      of bosonic atoms after suddenly switching on the tunnel coupling. The following
      phase dynamics is governed by the quantum sine-Gordon equation. In the
      semiclassical limit of weak interactions, we observe the parametric amplification
      of quantum fluctuations leading to the formation of breathers with a finite
      lifetime. The typical lifetime and density of these "quasibreathers" are derived
      employing exact solutions of the classical sine-Gordon equation. Both depend on
      the initial relative phase between the condensates, which is considered as a
      tunable parameter.

PMID- 23002757
TI  - Crystallization during bending of a Pd-based metallic glass detected by x-ray
      microscopy.
AB  - Without the availability of slip systems and dislocation glide as in crystalline
      materials, metallic glasses resist irreversible deformation to elastic strains of
      2% or more before undergoing heterogeneous plastic flow via the formation of
      shear bands. Observation of crystallite formation under compressive load was
      previously obtained by transmission electron microscopy. In this Letter, we
      present results of nondestructive x-ray diffraction microprofiling of the section
      of a bent glassy Pd40Cu30Ni10P20 ribbon in transmission using a synchrotron
      microbeam. Crystallization was clearly detected but only on the compression side
      of the neutral fiber. The experimental results and crystal nucleation frequency
      analysis are consistent with massive nucleation in shear bands forming under
      compressive stress but mainly for metallic glasses that show a large supercooled
      liquid temperature range DeltaT=T(x)-T(g) between glass transition at T(g) and
      crystallization at T(x). The phenomenon is sensitively dependent on the volume
      change that accompanies crystallization in the supercooled liquid temperature
      range where the much larger liquid-state thermal expansion coefficient
      significantly increases the specific volume difference between the liquid and
      crystalline states. The results are also consistent with the many reports of
      extensive strain to fracture of metallic glasses under compressive load but not
      under tension.

PMID- 23002758
TI  - Monolithic growth of ultrathin Ge nanowires on Si(001).
AB  - Self-assembled Ge wires with a height of only 3 unit cells and a length of up to
      2 micrometers were grown on Si(001) by means of a catalyst-free method based on
      molecular beam epitaxy. The wires grow horizontally along either the [100] or the
      [010] direction. On atomically flat surfaces, they exhibit a highly uniform,
      triangular cross section. A simple thermodynamic model accounts for the existence
      of a preferential base width for longitudinal expansion, in quantitative
      agreement with the experimental findings. Despite the absence of intentional
      doping, the first transistor-type devices made from single wires show low
      resistive electrical contacts and single-hole transport at sub-Kelvin
      temperatures. In view of their exceptionally small and self-defined cross
      section, these Ge wires hold promise for the realization of hole systems with
      exotic properties and provide a new development route for silicon-based
      nanoelectronics.

PMID- 23002759
TI  - Dynamical instability in Boolean networks as a percolation problem.
AB  - Boolean networks, widely used to model gene regulation, exhibit a phase
      transition between regimes in which small perturbations either die out or grow
      exponentially. We show and numerically verify that this phase transition in the
      dynamics can be mapped onto a static percolation problem which predicts the long
      time average Hamming distance between perturbed and unperturbed orbits.

PMID- 23002760
TI  - Microstructure map for self-organized phase separation during film deposition.
AB  - Drastically different two-phase microstructures have been reported for alloy
      epitaxial films, including self-organized nanoscale concentration modulations of
      vertical and lateral stripes. To understand the disparity of these
      microstructures, we study their formation mechanisms via spinodal decomposition
      during film deposition with the aid of computer simulations. Based on the
      simulation results, a microstructure map is established that describes
      relationships among the morphology of self-organized two-phase microstructure,
      initial alloy composition, and deposition rate relative to the phase separation
      kinetics in the film. Depending on the deposition rate relative to the kinetics
      of spinodal decomposition in the film, both laterally and vertically modulated
      microstructures could be obtained.

PMID- 23002762
TI  - Insulator-metal transition in highly compressed NiO.
AB  - The insulator-metal transition was observed experimentally in nickel monoxide
      (NiO) at very high pressures of ~240 GPa. The sample resistance becomes
      measurable at about 130 GPa and decreases substantially with the pressure
      increase to ~240 GPa. A sharp drop in resistance by about 3 orders of magnitude
      has been observed at ~240 GPa with a concomitant change of the resistance type
      from semiconducting to metallic. This is the first experimental observation of an
      insulator-metal transition in NiO, which was anticipated by Mott decades ago.
      From simple multielectron consideration, the metallic phase of NiO forms when the
      effective Hubbard energy U(eff) is almost equal to the estimated full bandwidth
      2W.

PMID- 23002761
TI  - Three-dimensional electron realm in VSe2 by soft-x-ray photoelectron
      spectroscopy: origin of charge-density waves.
AB  - The resolution of angle-resolved photoelectron spectroscopy (ARPES) in three
      dimensional (3D) momentum k is fundamentally limited by ill defined surface
      perpendicular wave vector k(perpendicular) associated with the finite
      photoelectron mean free path. Pushing ARPES into the soft-x-ray energy region
      sharpens the k(perpendicular) definition, allowing accurate electronic structure
      investigations in 3D materials. We apply soft-x-ray ARPES to explore the 3D
      electron realm in a paradigm transition metal dichalcogenide VSe2. Essential to
      break through the dramatic loss of the valence band photoexcitation cross section
      at soft-x-ray energies is the advanced photon flux performance of our synchrotron
      instrumentation. By virtue of the sharp 3D momentum definition, the soft-x-ray
      ARPES experimental band structure and Fermi surface of VSe2 show a textbook
      clarity. We identify pronounced 3D warping of the Fermi surface and show that its
      concomitant nesting acts as the precursor for the exotic 3D charge-density waves
      in VSe2. Our results demonstrate the immense potential of soft-x-ray ARPES to
      explore details of 3D electronic structure.

PMID- 23002763
TI  - Kondo destruction and valence fluctuations in an Anderson model.
AB  - Unconventional quantum criticality in heavy-fermion systems has been extensively
      analyzed in terms of a critical destruction of the Kondo effect. Motivated by a
      recent demonstration of quantum criticality in a mixed-valent heavy-fermion
      system, beta-YbAlB(4), we study a particle-hole-asymmetric Anderson impurity
      model with a pseudogapped density of states. We demonstrate Kondo destruction at
      a mixed-valent quantum critical point, where a collapsing Kondo energy scale is
      accompanied by a singular charge-fluctuation spectrum. Both spin and charge
      responses scale with energy over temperature (omega/T) and magnetic field over
      temperature (H/T). Implications for unconventional quantum criticality in mixed
      valence heavy fermions are discussed.

PMID- 23002764
TI  - Breakdown of the Korringa law of nuclear spin relaxation in metallic GaAs.
AB  - We present nuclear spin relaxation measurements in GaAs epilayers using a new
      pump-probe technique in all-electrical, lateral spin-valve devices. The measured
      T(1) times agree very well with NMR data available for T>1 K. However, the
      nuclear spin relaxation rate clearly deviates from the well-established Korringa
      law expected in metallic samples and follows a sublinear temperature dependence
      T(1)(-1) is proportional to T(0.6) for 0.1 K<=T<=10 K. Further, we investigate
      nuclear spin inhomogeneities.

PMID- 23002765
TI  - Symmetry-driven novel Kondo effect in a molecule.
AB  - The Kondo effect caused by the adsorption of iron phthalocyanine (FePc) on
      Au(111) was investigated by the combination of density functional theory and a
      numerical renormalization group calculation with scanning tunneling microscopy.
      We found that a novel Kondo effect is realized for a single FePc molecule on
      Au(111) by tuning the symmetry of the ligand field through the local coordination
      to the substrate. For FePc in the on top configuration where fourfold symmetry
      around the Fe(2+) ion is held, the orbital degrees of freedom survive, resulting
      in the spin+orbital SU(4) Kondo effect. In contrast, the reduced symmetry in the
      bridge configuration freezes the orbital degrees of freedom, leading to the spin
      SU(2) Kondo effect. These results provide a novel example to manipulate the many
      body phenomena by tuning the local symmetry.

PMID- 23002766
TI  - Universal heat conduction in the iron arsenide superconductor KFe2As2: evidence
      of a d-wave state.
AB  - The thermal conductivity kappa of the iron arsenide superconductor KFe2As2 was
      measured down to 50 mK for a heat current parallel and perpendicular to the
      tetragonal c axis. A residual linear term at T->0, kappa(0)/T is observed for
      both current directions, confirming the presence of nodes in the superconducting
      gap. Our value of kappa(0)/T in the plane is equal to that reported by Dong et
      al. [Phys. Rev. Lett. 104, 087005 (2010)] for a sample whose residual resistivity
      rho(0) was 10 times larger. This independence of kappa(0)/T on impurity
      scattering is the signature of universal heat transport, a property of
      superconducting states with symmetry-imposed line nodes. This argues against an s
      wave state with accidental nodes. It favors instead a d-wave state, an assignment
      consistent with five additional properties: the magnitude of the critical
      scattering rate Gamma(c) for suppressing T(c) to zero; the magnitude of
      kappa(0)/T, and its dependence on current direction and on magnetic field; the
      temperature dependence of kappa(T).

PMID- 23002767
TI  - Scanning tunneling spectroscopy of superconducting LiFeAs single crystals:
      evidence for two nodeless energy gaps and coupling to a bosonic mode.
AB  - The superconducting compound LiFeAs is studied by scanning tunneling microscopy
      and spectroscopy. A gap map of the unreconstructed surface indicates a high
      degree of homogeneity in this system. Spectra at 2 K show two nodeless
      superconducting gaps with Delta(1)=5.3+/-0.1 meV and Delta(2)=2.5+/-0.2 meV. The
      gaps close as the temperature is increased to the bulk T(c), indicating that the
      surface accurately represents the bulk. A dip-hump structure is observed below
      T(c) with an energy scale consistent with a magnetic resonance recently reported
      by inelastic neutron scattering.

PMID- 23002768
TI  - Drastic suppression of noise-induced errors in underdamped long Josephson
      junctions.
AB  - The fluctuational propagation of solitons (magnetic fluxons) in long Josephson
      junctions is studied both numerically and analytically. It is demonstrated that
      operation in conditions where solitons are subjected to Lorentz contraction for a
      significant part of the junctions length leads to drastic suppression of thermal
      jitter at the output junction end. Specifically, for large-to-critical damping
      and small values of bias current, the physically obvious dependence of the jitter
      versus length sigma~?L is confirmed, while for small damping starting from the
      experimentally relevant alpha=0.1 and below, strong deviation from sigma~?L is
      observed, up to nearly complete independence of the jitter versus length, which
      is supported by the obtained theory.

PMID- 23002769
TI  - Observation of Andreev bound states at spin-active interfaces.
AB  - We report on high-resolution differential conductance experiments on nanoscale
      superconductor-ferromagnet tunnel junctions with ultrathin oxide tunnel barriers.
      We observe subgap conductance features that are symmetric with respect to bias
      and shift according to the Zeeman energy with an applied magnetic field. These
      features can be explained by resonant transport via Andreev bound states induced
      by spin-active scattering at the interface. From the energy and Zeeman shift of
      the bound states, both the magnitude and sign of the spin-dependent interfacial
      phase shifts between spin-up and spin-down electrons can be determined. These
      results contribute to the microscopic insight into the triplet proximity effect
      at spin-active interfaces.

PMID- 23002770
TI  - Perpendicular magnetization and generic realization of the Ising model in
      artificial spin ice.
AB  - We have studied frustrated kagome arrays and unfrustrated honeycomb arrays of
      magnetostatically interacting single-domain ferromagnetic islands with
      magnetization normal to the plane. The measured pairwise spin correlations of
      both lattices can be reproduced by models based solely on nearest-neighbor
      correlations. The kagome array has qualitatively different magnetostatics but
      identical lattice topology to previously studied artificial spin ice systems
      composed of in-plane moments. The two systems show striking similarities in the
      development of moment pair correlations, demonstrating a universality in
      artificial spin ice behavior independent of specific realization in a particular
      material system.

PMID- 23002771
TI  - Magnonic domain wall heat conductance in ferromagnetic wires.
AB  - We present a theoretical study of magnon-mediated heat transport in electrically
      insulating ferromagnetic wires containing a domain wall (DW). In the regime of
      validity of continuum micromagnetism, a DW is found to have no effect on the heat
      conductance. However, spin waves are found to be reflected by DWs with widths of
      a few lattice spacings, which is associated with emergence of an additional spin
      wave bound state. The resulting DW heat conductance should be significant for
      thin films of yttrium iron garnet with sharply defined magnetic domains.

PMID- 23002772
TI  - Relaxation time of terahertz magnons excited at ferromagnetic surfaces.
AB  - The temporal and spatial properties of terahertz magnons excited at ferromagnetic
      fcc Co(100) and bcc Fe(110) surfaces are investigated experimentally. The magnon
      lifetime is found to be a few tens of femtoseconds at low wave vectors, which
      reduces significantly as the wave vector approaches the Brillouin zone boundary.
      Surprisingly, the lifetime is very similar in both systems, in spite of the fact
      that the excitation energy in the Co(100) film is by a factor of two larger than
      in the Fe(110) film. The magnon wave packets propagate only a few nanometers
      within their lifetime. In addition to the fact that our results describe the
      damping mechanism in ultrafast time scales, they may provide a way to predict the
      ultimate time scale of magnetic switching in nanostructures.

PMID- 23002773
TI  - Attosecond time-resolved photoemission from core and valence states of magnesium.
AB  - We report on laser-assisted attosecond photoemission from single-crystalline
      magnesium. In strong contrast to the previously investigated transition metal
      tungsten, photoelectron wave packets originating from the localized core level
      and delocalized valence-band states are launched simultaneously from the solid
      within the experimental uncertainty of 20 as. This phenomenon is shown to be
      compatible with a heuristic model based on free-particle-like propagation of the
      electron wave packets generated inside the crystal by the attosecond excitation
      pulse and their subsequent interaction with the assisting laser field at the
      metal-vacuum interface.

PMID- 23002774
TI  - Proposed nonlinear resonance laser technique for manipulating nanoparticles.
AB  - We propose nonlinear resonant laser manipulation, a technique that drastically
      enhances the number of degrees of freedom when manipulating nano-objects.
      Considering the high laser intensity required to trap single molecules, we
      calculate the radiation force exerted on a molecule in a focused laser beam by
      solving the density matrix equations using the nonperturbative method. The
      results coherently elucidate certain recently reported puzzling phenomena that
      contradict the conventional understanding of laser trapping. Further, we
      demonstrate unconventional forms of laser manipulations using "stimulated recoil
      force" and "subwavelength laser manipulation."

PMID- 23002775
TI  - Geometry-controlled interface localization-delocalization transition in block
      copolymers.
AB  - Lamellar copolymers confined into a film of thickness D by two stripe-patterned
      surfaces, which are rotated against each other by a twist angle alpha, form
      lamellar domains that register and align with the respective chemical surface
      patterns. The two domains of thickness x and D-x are separated by an interface
      that resembles a twist grain boundary. At small twist angles alpha or strong
      selectivity of the surface patterns, this interface fluctuates around the middle
      of the film, x~D/2, while the interface is localized at one of the surfaces, x~0
      or x~D, in the opposite limit. These two morphologies are separated by an
      interface localization-delocalization transition (ILDT) that can be controlled by
      the twist angle alpha. For thin films, we find a second-order ILDT while the ILDT
      is first-order for large D values. A phenomenological interface Hamiltonian is
      used to relate the findings to the ILDT of symmetric mixtures, and the
      predictions are confirmed by molecular simulation.

PMID- 23002776
TI  - Mutational pathway determines whether drug gradients accelerate evolution of drug
      resistant cells.
AB  - Drug gradients are believed to play an important role in the evolution of
      bacteria resistant to antibiotics and tumors resistant to anticancer drugs. We
      use a statistical physics model to study the evolution of a population of
      malignant cells exposed to drug gradients, where drug resistance emerges via a
      mutational pathway involving multiple mutations. We show that a nonuniform drug
      distribution has the potential to accelerate the emergence of resistance when the
      mutational pathway involves a long sequence of mutants with increasing
      resistance, but if the pathway is short or crosses a fitness valley, the
      evolution of resistance may actually be slowed down by drug gradients. These
      predictions can be verified experimentally, and may help to improve strategies
      for combating the emergence of resistance.

PMID- 23002777
TI  - Plasmonic complex fluids of nematiclike and helicoidal self-assemblies of gold
      nanorods with a negative order parameter.
AB  - We describe a soft matter system of self-organized oblate micelles and plasmonic
      gold nanorods that exhibit a negative orientational order parameter. Because of
      anisotropic surface anchoring interactions, colloidal gold nanorods tend to align
      perpendicular to the director describing the average orientation of normals to
      the discoidal micelles. Helicoidal structures of highly concentrated nanorods
      with a negative order parameter are realized by adding a chiral additive and are
      further controlled by means of confinement and mechanical stress. Polarization
      sensitive absorption, scattering, and two-photon luminescence are used to
      characterize orientations and spatial distributions of nanorods. Self-alignment
      and effective-medium optical properties of these hybrid inorganic-organic complex
      fluids match predictions of a simple model based on anisotropic surface anchoring
      interactions of nanorods with the structured host medium.

PMID- 23002778
TI  - Dynamic crossover scaling in polymer solutions.
AB  - The crossover region in the phase diagram of polymer solutions, in the regime
      above the overlap concentration, is explored by Brownian dynamics simulations to
      map out the universal crossover scaling functions for the gyration radius and the
      single-chain diffusion constant. Scaling considerations, our simulation results,
      and recently reported data on the polymer contribution to the viscosity obtained
      from rheological measurements on DNA systems support the assumption that there
      are simple relations between these functions, such that they can be inferred from
      one another.

PMID- 23002779
TI  - First passage time for random walks in heterogeneous networks.
AB  - The first passage time (FPT) for random walks is a key indicator of how fast
      information diffuses in a given system. Despite the role of FPT as a fundamental
      feature in transport phenomena, its behavior, particularly in heterogeneous
      networks, is not yet fully understood. Here, we study, both analytically and
      numerically, the scaling behavior of the FPT distribution to a given target node,
      averaged over all starting nodes. We find that random walks arrive quickly at a
      local hub, and therefore, the FPT distribution shows a crossover with respect to
      time from fast decay behavior (induced from the attractive effect to the hub) to
      slow decay behavior (caused by the exploring of the entire system). Moreover, the
      mean FPT is independent of the degree of the target node in the case of compact
      exploration. These theoretical results justify the necessity of using a random
      jump protocol (empirically used in search engines) and provide guidelines for
      designing an effective network to make information quickly accessible.

PMID- 23002781
TI  - Dispersions of non-covalently functionalized graphene with minimal stabilizer.
AB  - We demonstrate that functionalized pyrene derivatives effectively stabilize
      single- and few-layer graphene flakes in aqueous dispersions. The
      graphene/stabilizer yield obtained by this method is exceptionally high relative
      to conventional nanomaterial stabilizers such as surfactants or polymers. The
      mechanism of stabilization by pyrene derivatives is investigated by studying the
      effects of various parameters on dispersed graphene concentration and stability;
      these parameters include stabilizer concentration, initial graphite
      concentration, solution pH, and type and number of functional groups and
      counterions. The effectiveness of the pyrene derivatives is pH-tunable, as
      measured by zeta potential, and is also a function of the number of functional
      groups, the electronegativity of the functional group, the counterion, the
      relative polarity between stabilizer and solvent, and the distance from the
      functional group to the basal plane. Even if the dispersion is destabilized by
      extreme pH or lyophilization, the graphene does not aggregate because the
      stabilizer remains adsorbed on the surface. These dispersions also show promise
      for applications in graphene/polymer nanocomposites (examined in this paper),
      organic solar cells, conductive films, and inkjet-printed electronic devices.

PMID- 23002782
TI  - Nontargeted metabolomics approach for age differentiation and structure
      interpretation of age-dependent key constituents in hairy roots of Panax ginseng.
AB  - The age of the ginseng plant has been considered as an important criterion to
      determine the quality of this species. For age differentiation and structure
      interpretation of age-dependent key constituents of Panax ginseng, hairy root
      (fine root) extracts aged from four to six years were analyzed using a
      nontargeted approach with ultraperformance liquid chromatography/quadrupole time
      of-flight mass spectrometry (UPLC-QTOFMS). Various classification methods were
      used to determine an optimal method to best describe ginseng age by selecting
      influential metabolites of different ages. Through the metabolite selection
      process, several age-dependent key constituents having the potential to be
      biomarkers were determined, and their structures were identified according to
      tandem mass spectrometry and accurate mass spectrometry by comparing them with an
      in-house ginsenoside library and with literature data. This proposed method
      applied to the hairy roots of P. ginseng showed an improved efficiency of age
      differentiation when compared to previous results on the main roots and increases
      the possibility of the identification of key metabolites that can be used as
      biomarker candidates for quality assurance in ginseng.

PMID- 23002780
TI  - Effects of glaucoma on Chrna6 expression in the retina.
AB  - PURPOSE: Recent advances in technology now provide tools capable of tracking
      genome-wide expression changes occurring in progressive pathological processes.
      The present experiments were carried out to determine if acetylcholine receptor
      alpha 6 subunit (Chrna6) is a reliable retinal ganglion cell (RGC) marker in
      adult mouse eyes and if Chrna6 expression can be used to track progressive loss
      of RGCs, such as is observed in the DBA/2J glaucoma model. METHODS: Data sets
      derived from the BXD strains were used to extract gene expression signatures for
      RGCs. Pooled retinas from DBA/2J or C57BL/6J cases at 1-3 months, 12 months, and
      16-17 months were prepared for gene-array and RT-PCR analysis. Globes were fixed
      in paraformaldehyde and sectioned for immunofluorescence with antibodies against
      Chrna6. RESULTS: Chrna6 has a cellular expression signature for RGCs with high
      correlation to Thy1 (r = 0.65), a recognized RGC marker. Immunofluorescence
      experiments confirm that in the young and adult mouse retina, Chrna6 is
      preferentially expressed by RGCs. We further show that C3H/HeJ retinas, which
      lack photoreceptors, also express Chrna6 in the RGC layer. Gene expression array
      analyses, confirmed by RT-PCR, show progressive loss of Chrna6 expression in
      retinas of the DBA/2J glaucomatous mouse retinas. CONCLUSIONS: Quantitative trait
      locus analysis provides support for Chrna6 as a RGC marker. Chrna6 expression
      decreases with death of RGCs in glaucomatous DBA/2J mice and after optic nerve
      crush injury, further supporting Chrna6 as a reliable RGC marker. High expression
      of RGC Chrna6 in the absence of photoreceptors is suggestive that Chrna6
      expression by RGCs is independent of photoreceptor-derived stimuli.

PMID- 23002783
TI  - Novel hybrid laparoscopic sacrocolpopexy for pelvic organ prolapse with a severe
      paravaginal defect.
AB  - Abdominal sacrocolpopexy is the gold standard for treating pelvic organ prolapse
      (POP) because of safety and durable good results. More recently laparoscopic
      sacrocolpopexy (LSC), a less invasive approach, has become popular. Although
      these surgeries are versatile and can treat almost all patients with POP, these
      techniques have shortcomings. Specifically, reinforcement of lateral vaginal
      defects are not very strong, thus patients with POP and a severe paravaginal
      defect are not good candidates for abdominal or laparoscopic sacrocolpopexy. To
      overcome this problem, we developed a novel type of LSC, which can reinforce
      severe paravaginal defects by using a reversed T-shaped anterior mesh combining
      the advantage of transvaginal mesh surgery. We refer to this novel surgery as
      'hybrid LSC'. Thus far, eight patients have successfully undergone this surgery.
      Hybrid LSC is a simple and secure method, and is an alternative treatment for POP
      with a severe paravaginal defect.

PMID- 23002784
TI  - The influence of therapist variance on the dependability of therapists' alliance
      scores: a brief comment on "The dependability of alliance assessments: the
      alliance-outcome correlation is larger than you think" (Crits-Christoph et al.,
      2011).
AB  - OBJECTIVE: Crits-Christoph, Connolly Gibbons, Hamilton, Ring-Kurtz, and Gallop
      (2011) used generalizability theory to critique the measurement of the
      therapeutic alliance in psychotherapy research, showing that the dependability of
      alliance scores may be quite low, which in turn can lead to attenuated alliance
      outcome correlation estimates. METHOD AND RESULTS: Two extensions to Crits
      Christoph et al.'s critique are presented that can greatly influence
      dependability of therapist scores and are particularly relevant to researchers
      wishing to study process-outcome correlations at the therapist level.
      Specifically, the authors show how the intraclass correlation and the number of
      therapists affect both the magnitude and precision of generalizability
      coefficients. CONCLUSIONS: The authors note that attending to issues raised in
      this article and Crits-Christoph et al. (2011) in future process-outcome research
      will improve the accuracy of the conclusions about process-outcome correlations.

PMID- 23002785
TI  - Acute pancreatitis in chronic kidney disease--a common but often misunderstood
      combination.
AB  - The occurrence of pancreatitis has been reported among chronic kidney disease
      (CKD) patients, especially those who are on peritoneal dialysis. It contributes
      to an increased morbidity and mortality in patients who are already suffering
      from renal failure. The diagnosis of acute pancreatitis is also modified by the
      loss of renal function with altered levels of pancreatic enzyme estimation and
      the contribution of pancreatic damage due to uremia and dialysis. We describe two
      cases of CKD who presented with acute pancreatitis and also briefly review the
      literature.

PMID- 23002786
TI  - Expert judgments about RD&D and the future of nuclear energy.
AB  - Probabilistic estimates of the cost and performance of future nuclear energy
      systems under different scenarios of government research, development, and
      demonstration (RD&D) spending were obtained from 30 U.S. and 30 European nuclear
      technology experts. We used a novel elicitation approach which combined
      individual and group elicitation. With no change from current RD&D funding
      levels, experts on average expected current (Gen. III/III+) designs to be
      somewhat more expensive in 2030 than they were in 2010, and they expected the
      next generation of designs (Gen. IV) to be more expensive still as of 2030.
      Projected costs of proposed small modular reactors (SMRs) were similar to those
      of Gen. IV systems. The experts almost unanimously recommended large increases in
      government support for nuclear RD&D (generally 2-3 times current spending). The
      majority expected that such RD&D would have only a modest effect on cost, but
      would improve performance in other areas, such as safety, waste management, and
      uranium resource utilization. The U.S. and E.U. experts were in relative
      agreement regarding how government RD&D funds should be allocated, placing
      particular focus on very high temperature reactors, sodium-cooled fast reactors,
      fuels and materials, and fuel cycle technologies.

PMID- 23002787
TI  - Flying blind: the experience of online interprofessional facilitation.
AB  - The role of the facilitator is known to be important in fostering productive
      interprofessional education (IPE) in the face-to-face (F2F) environment. Online
      learning can help surmount some of the logistical challenges in IPE by bringing
      together diverse professionals in multiple geographical locations. Best practices
      in F2F IPE facilitation are beginning to emerge, but there is scant literature
      examining IPE facilitation online. What little research exists has focused on the
      asynchronous environment and suggests that the skill sets of online and F2F
      facilitators have considerable overlap, but there are further demands in the
      online setting. This qualitative study sought to examine online synchronous IPE
      facilitation through the self-reported experiences of seven trained facilitators
      during a 12-week online course. Data collected through focus groups and targeted
      interviews were analyzed by the research team using constant comparison
      techniques. Four major themes were revealed: technology as a dynamic force,
      reduction in non-verbal cues, evolution of the online IPE group process over time
      and the importance of co-facilitation. The foundations of IPE facilitation were
      seen to carry over to the online setting. This study has implications for the
      training of IPE facilitators and for the design of online IPE learning
      experiences. 

PMID- 23002788
TI  - Not left to chance: introducing an undergraduate interprofessional education
      curriculum.
AB  - Teaching diverse health profession students to work in teams, communicate,
      understand each other's roles and responsibilities, and effectively collaborate
      is imperative for creating a practice-ready workforce. This short report
      introduces an innovative undergraduate interprofessional curriculum for students
      enrolled in the baccalaureate majors of applied exercise science, athletic
      training, dental hygiene, nursing and pre-occupational therapy. The process of
      designing this program of study, guided by the method of appreciative inquiry, is
      highlighted. The format and learning activities created for this novel curriculum
      are described. Congruence for this endeavor is explored through alignment with
      the recent national Interprofessional Education Collaborative expert panel
      report. Preparing graduates to fulfill the dual identity of discipline-specific
      clinician and interprofessional team member is an essential curricular
      consideration for contemporary health profession education.

PMID- 23002789
TI  - Silver(I)-catalyzed deprotection of p-methoxybenzyl ethers: a mild and
      chemoselective method.
AB  - The p-methoxybenzyl protecting group (PMB) on various alcohols and an acid was
      efficiently and selectively cleaved by the action of a catalytic amount of
      silver(I) hexafluoroantimonate combined with 0.5 equiv of 1,3,5-trimethoxybenzene
      in dichloromethane at 40  degrees C.

PMID- 23002790
TI  - Co-occupant's exposure to exhaled pollutants with two types of personalized
      ventilation strategies under mixing and displacement ventilation systems.
AB  - Personalized ventilation (PV) system in conjunction with total ventilation system
      can provide cleaner inhaled air for the user. Concerns still exist about whether
      the normally protecting PV device, on the other hand, facilitates the dispersion
      of infectious agents generated by its user. In this article, two types of PV
      systems with upward supplied fresh air, namely a chair-based PV and one kind of
      desk-mounted PV systems, when combined with mixing ventilation (MV) and
      displacement ventilation (DV) systems, are investigated using simulation method
      with regard to their impacts on co-occupant's exposure to the exhaled droplet
      nuclei generated by the infected PV user. Simulation results of tracer gas and
      particles with aerodynamic diameter of 1, 5, and 10 MUm from exhaled air show
      that, when only the infected person uses a PV, the different PV air supplying
      directions present very different impacts on the co-occupant's intake under DV,
      while no apparent differences can be observed under MV. The findings demonstrate
      that better inhaled air quality can always be achieved under DV when the adopted
      PV system can deliver conditioned fresh air in the same direction with the mainly
      upward airflow patterns of DV.

PMID- 23002791
TI  - The role of angiotensin II on sodium appetite after a low-sodium diet.
AB  - The present study aimed to investigate the role of angiotensin II (Ang II) on
      sodium appetite in rats subjected to a normal or a low-sodium diet (1% or > 0.1%
      NaCl) for 4 days. During sodium restriction, a reduction in water intake, urinary
      volume and sodium excretion was observed. After a low-sodium diet, we observed
      decreased plasma protein concentrations and haematocrit associated with a slight
      reduction in arterial pressure, without any significant changes in heart rate,
      natraemia, corticotrophin-releasing hormone mRNA expression in the
      paraventricular nucleus and corticosterone levels. After providing hypertonic
      saline, there was an increase in saline intake followed by a small increase in
      water intake, resulting in an enhanced saline intake ratio and the recovery of
      arterial pressure. Sodium deprivation increased plasma but not brain Ang I and II
      concentrations. A low-sodium diet increased kidney renin and liver
      angiotensinogen mRNA levels but not lung angiotensin-converting enzyme mRNA
      expression. Moreover, Ang II type 1a receptor mRNA expression was increased in
      the subfornical organ and the dorsal raphe nucleus and decreased in the medial
      preoptic nuclei, without changes in the paraventricular nucleus and the nucleus
      of solitary tract after a low-sodium diet. Blockade of AT(1)  receptors or brain
      Ang II synthesis led to a reduction in sodium intake after a low-sodium diet.
      Intracerebroventricular injection of Ang II led to a similar increase in sodium
      and water intake in the control and low-sodium diet groups. In conclusion, the
      results of the present study suggest that Ang II is involved in the increased
      sodium appetite after a low-sodium diet.

PMID- 23002792
TI  - Effect of forced transitions on the most functionally impaired nursing home
      residents.
AB  - OBJECTIVES: To examine the hospitalization rate and mortality associated with
      forced mass transfer of nursing home (NH) residents with the highest levels of
      functional impairment. DESIGN: Retrospective cohort study. SETTING: One hundred
      nineteen Texas and Louisiana NHs identified as being at risk for evacuation for
      Hurricane Gustav. PARTICIPANTS: Six thousand four hundred sixty-four long-stay
      residents residing in at-risk NHs for at least three consecutive months before
      landfall of Hurricane Gustav. MEASUREMENTS: Using Medicare claims and
      instrumental variable analysis, the mortality (death at 30 and 90 days) and
      hospitalization rates (at 30 and 90 days) of the most functionally impaired long
      stay residents who were evacuated for Hurricane Gustav were compared with those
      of the most functionally impaired residents who did not evacuate. RESULTS: The
      effect of evacuation was associated with 8% more hospitalizations by 30 and 90
      days for the most functionally impaired residents. Evacuation was not
      significantly related to mortality. CONCLUSION: The most functionally impaired NH
      residents experience more hospitalizations but not mortality as a consequence of
      forced mass transfer. With the inevitability of NH evacuations for many different
      reasons, harm mitigation strategies focused on the most impaired residents are
      needed.

PMID- 23002793
TI  - Testing for homogeneity of multivariate dispersions using dissimilarity measures.
AB  - Testing homogeneity of dispersions may be of its own scientific interest as well
      as an important auxiliary step verifying assumptions of a main analysis. The
      problem is that many biological and ecological data are highly skewed and zero
      inflated. Also the number of variables often exceeds the sample size. Thus data
      analysts often do not rely on parametric assumptions, but use a particular
      dissimilarity measure to calculate a matrix of pairwise differences. This matrix
      is then the basis for further statistical inference. Anderson (2006) proposed a
      distance-based test of homogeneity of multivariate dispersions for a one-way
      ANOVA design, for which a matrix of pairwise dissimilarities can be taken as an
      input. The key idea, like in Levene's test, is to replace each observation with
      its distance to an estimated group center. In this paper we suggest an
      alternative approach that is based on the means of within-group distances and
      does not require group centre calculations to obtain the test statistic. We show
      that this approach can have theoretical as well as practical advantages. A
      permutation procedure that gives type I error close to the prescribed value even
      in small samples is described.

PMID- 23002794
TI  - Dynamic migration of a mobile plaque from the brachiocephalic artery detected by
      ultrasonography.

PMID- 23002795
TI  - Association between pre-eclampsia and inherited thrombophilias.
AB  - OBJECTIVE: The aim was to determine whether inherited thrombophilia increases the
      risk of pre-eclampsia (PE) or interferes with its clinical course. MATERIAL AND
      METHODS: We included 50 patients with severe PE and 50 healthy pregnant women.
      Patients were evaluated for inherited thrombophilia. RESULTS: Fourteen patients
      in the study group was factor V Leiden (FVL) carrier while it was 12% in the
      control group. In women with PE, FVL and other inherited thrombophilic factors
      were not more prevalent than in the controls. CONCLUSION: The present study
      failed to demonstrate an association between the inherited thrombophilias and PE.

PMID- 23002796
TI  - Should college campuses become tobacco free without an enforcement plan?
AB  - Tobacco-free campuses are a great public health initiative. Healthy People 2020
      and Healthy Campus 2020 address tobacco use and young adults including college
      students. Sources indicate that of the more than 6,000 colleges and universities
      in the United States, less than 800 are either smoke free or tobacco free. An
      increasing number of college campus policy makers in the United States are
      implementing smoke-free or tobacco-free policies, including procedures for
      violators of these policies. However, without a clearly defined and actionable
      enforcement component, these policies serve little purpose. This has become a
      policy enforcement issue that campus leaders should address. Should colleges and
      universities become tobacco free, if enforcement is not implemented? College and
      university administrators should demonstrate leadership by having violators of
      tobacco-free campus policies held to the same standard as those who violate other
      policies.

PMID- 23002797
TI  - Measuring compliance with tobacco-free campus policy.
AB  - OBJECTIVE: The purpose is to describe psychometric testing and feasibility of the
      Tobacco-Free Compliance Assessment Tool (TF-CAT) to measure tobacco-free policy
      compliance at a public university and medical center. The aims are to (1)
      investigate concurrent validity by comparing the number of cigarette butts in
      areas covered by the policy with those on adjacent sidewalks; (2) evaluate the
      interrater reliability of the TF-CAT; and (3) describe the feasibility of using
      the TF-CAT. METHODS: Phase I was a pilot study on the health care campus. Phase
      II was baseline of an intervention study on the main campus. Cigarette butts and
      smokers were counted in hot spots. Validity was assessed using Mann-Whitney U and
      Geographical Information System Analysis methods. RESULTS: There was some support
      for the validity and high interrater reliability. Data collectors spent 1 hour
      per week for 8 weeks during Phase I, and 31 hours in 1 week during Phase II.
      CONCLUSION: TF-CAT is a feasible, time-intensive method to measure tobacco-free
      policy compliance.

PMID- 23002798
TI  - Changes in smoking prevalence, attitudes, and beliefs over 4 years following a
      campus-wide anti-tobacco intervention.
AB  - OBJECTIVE: The current study examined the effectiveness of an institutional
      intervention aimed at decreasing prevalence of tobacco use and exposure to smoke
      on campus over a 4-year period. PARTICIPANTS: Participants were undergraduate
      students (N = 4,947) enrolled at a large Midwestern university between 2007 and
      2010. METHODS: In 2008, tobacco use was banned on campus. Additionally, campus
      wide tobacco cessation services and information were provided to all students. A
      self-report measure assessing demographics, smoking prevalence, attitudes, and
      smoke exposure was administered at baseline and at 3 time points over the
      following 3 years. RESULTS: The percentage of more frequent smokers and less
      frequent smokers decreased across assessment points. The program appeared to be
      less effective for female smokers than male smokers. Further, a significant
      change in attitudes and secondhand smoke exposure was observed. CONCLUSIONS: It
      appears that a campus-wide tobacco ban is a well-accepted and effective
      prevention method for smoking. This study lends considerable support for efforts
      towards smoke-free campuses.

PMID- 23002799
TI  - Assessment of college and university campus tobacco-free policies in North
      Carolina.
AB  - OBJECTIVE: To develop a reliable and efficient method for assessing prevalence
      and strength of college/university tobacco-related policies. PARTICIPANTS: North
      Carolina (NC) public universities, community colleges, and private
      colleges/universities (N = 110). METHODS: A census of policies using campus
      handbooks and Web sites was conducted in March 2011. RESULTS: The rating tool is
      reliable and valid. Ninety-nine percent of NC college/university campuses are
      smoke-free in all indoor areas. The majority (94/110 [85%]) of colleges and
      universities regulate smoking and/or tobacco in some or all outdoor areas. Less
      than 20% of campuses had restrictions for industry marketing, promotion, and
      sales. CONCLUSIONS: Clean indoor air policies are present at all but 1 NC
      college/university campus, and a growing number have enacted broad outdoor limits
      to protect students, faculty, and staff from secondhand smoke. Policy census
      approaches across all other states would quantify the national tobacco-free
      college campus policy environment and facilitate adoption of tobacco-free campus
      policies.

PMID- 23002801
TI  - Waterpipe smoking among students in one US university: predictors of an intention
      to quit.
AB  - OBJECTIVE: To examine the intention to quit waterpipe smoking among college
      students. PARTICIPANTS: A total of 276 University of Houston students identified
      through an online survey administered in February 2011. Participants indicated
      they had smoked a waterpipe in the month prior to the survey. METHODS: Cross
      sectional study. Questions included demographics, tobacco use, perceived risk of
      waterpipe smoking, and social acceptability. Multivariate logistic regression was
      used to determine predictors of an intention to quit. RESULTS: Most of the sample
      participants (n = 227; 83%) reported that they had no intention to quit. Students
      believing that waterpipe smoking was harmful were more likely to have an
      intention to quit (odd ratio [OR] = 2.38, 95% confidence interval [CI; 1.05,
      5.36]). Those who smoked for more than 60 minutes were less likely to have a
      desire to quit (OR = 0.29, 95% CI [0.12, 0.73]). CONCLUSIONS: The low level of a
      desire to quit demonstrated underscores the urgent need to develop interventions
      that educate users about expected harms of continued use.

PMID- 23002800
TI  - A multiyear survey of waterpipe and cigarette smoking on a US university campus.
AB  - OBJECTIVES: To examine the prevalence and characteristics of dual users of
      cigarettes and waterpipes by comparing them with individuals who use either
      product exclusively. PARTICIPANTS: Cross-sections of undergraduate students at a
      public university recruited each spring semester from 2006 to 2011 (total N =
      2,998). METHODS: Participants completed an Internet survey that assessed
      demographics, tobacco use, perceptions, and norms concerning various tobacco
      products. Individuals who reported exclusive cigarette, exclusive waterpipe, and
      dual (waterpipe + cigarette) use were examined. RESULTS: Across years, 22%
      reported exclusive cigarette, 6.1% exclusive waterpipe, and 9.3% dual cigarette
      and waterpipe use. Dual users differed in demographics and social influences from
      their exclusive counterparts. CONCLUSIONS: Findings suggest that dual waterpipe
      and cigarette use was more prevalent than exclusive waterpipe use, and dual users
      may differ from individuals who use either product alone. These results warrant
      the inclusion of waterpipe-specific content in state and national surveys as well
      as tobacco prevention and intervention efforts.

PMID- 23002802
TI  - Using the photovoice method to advocate for change to a campus smoking policy.
AB  - OBJECTIVE: The authors used the photovoice method as a strategy for empowering
      students to advocate for change of a campus smoking policy. PARTICIPANTS:
      Participants included 49 college students and 160 photo-exhibit attendees during
      spring 2011. METHODS: Students were trained in the use of the photovoice method
      and a public exhibit was used to educate the campus community and advocate for
      change. RESULTS: The photovoice initiative resulted in an effective platform for
      students to successfully advocate for the relocation of ashtrays that were in
      violation of the policy and for the elicitation of future advocacy targets.
      CONCLUSIONS: The photovoice project provided a platform for students to have
      their views heard by campus community members and policymakers. The project
      served as a useful tool for grassroots student advocacy. Those interested in
      addressing campus health policy issues may want to consider conducting a
      photovoice project similar to the one described in this article.

PMID- 23002804
TI  - Meta-analysis: effect of preoperative infliximab use on early postoperative
      complications in patients with ulcerative colitis undergoing abdominal surgery.
AB  - BACKGROUND: Infliximab is widely used in severe and refractory ulcerative colitis
      (UC). The results of clinical studies are inconsistent on whether preoperative
      infliximab use increases early postoperative complications in UC patients. AIM:
      To determine the clinical safety and efficacy of preoperative infliximab
      treatment in UC patients with regard to short-term outcomes following abdominal
      surgery. METHODS: PubMed, Embase databases were searched for controlled
      observational studies comparing postsurgical morbidity in UC patients receiving
      infliximab preoperatively with those not on infliximab. The primary endpoint was
      total complication rate. Secondary endpoints included the rate of infectious and
      non-infectious complications. We calculated pooled odds ratios (ORs) with 95%
      confidence intervals (CIs) as summary measures. RESULTS: A total of 13 studies
      involving 2933 patients were included in our meta-analysis. There was no
      significant association between infliximab therapy preoperatively and total (OR =
      1.09, 95% CI: 0.87-1.37, P = 0.47), infectious (OR = 1.10, 95% CI: 0.51-2.38, P =
      0.81) and non-infectious (OR = 1.10, 95% CI: 0.76-1.59, P = 0.61) postoperative
      complications respectively. Infliximab might be a protective factor against
      infection for the use within 12 weeks prior to surgery (OR = 0.43, 95% CI: 0.22
      0.83, P = 0.01). No publication bias was found. CONCLUSION: Preoperative
      infliximab use does not increase the risk of early postoperative complications in
      patients with ulcerative colitis undergoing abdominal surgery.

PMID- 23002805
TI  - Radically enhanced molecular switches.
AB  - The mechanism governing the redox-stimulated switching behavior of a tristable
      [2]rotaxane consisting of a cyclobis(paraquat-p-phenylene) (CBPQT(4+)) ring
      encircling a dumbbell, containing tetrathiafulvalene (TTF) and 1,5
      dioxynaphthalene (DNP) recognition units which are separated from each other
      along a polyether chain carrying 2,6-diisopropylphenyl stoppers by a 4,4'
      bipyridinium (BIPY(2+)) unit, is described. The BIPY(2+) unit acts to increase
      the lifetime of the metastable state coconformation (MSCC) significantly by
      restricting the shuttling motion of the CBPQT(4+) ring to such an extent that the
      MSCC can be isolated in the solid state and is stable for weeks on end. As
      controls, the redox-induced mechanism of switching of two bistable [2]rotaxanes
      and one bistable [2]catenane composed of CBPQT(4+) rings encircling dumbbells or
      macrocyclic polyethers, respectively, that contain a BIPY(2+) unit with either a
      TTF or DNP unit, is investigated. Variable scan-rate cyclic voltammetry and
      digital simulations of the tristable and bistable [2]rotaxanes and [2]catenane
      reveal a mechanism which involves a bisradical state coconformation (BRCC) in
      which only one of the BIPY(*+) units in the CBPQT(2(*+)) ring is oxidized to the
      BIPY(2+) dication. This observation of the BRCC was further confirmed by
      theoretical calculations as well as by X-ray crystallography of the [2]catenane
      in its bisradical tetracationic redox state. It is evident that the incorporation
      of a kinetic barrier between the donor recognition units in the tristable
      [2]rotaxane can prolong the lifetime and stability of the MSCC, an observation
      which augurs well for the development of nonvolatile molecular flash memory
      devices.

PMID- 23002806
TI  - Improved transfer of graphene for gated Schottky-junction, vertical, organic,
      field-effect transistors.
AB  - An improved process for graphene transfer was used to demonstrate high
      performance graphene enabled vertical organic field effect transistors (G-VFETs).
      The process reduces disorder and eliminates the polymeric residue that typically
      plagues transferred films. The method also allows for purposely creating pores in
      the graphene of a controlled areal density. Transconductance observed in G-VFETs
      fabricated with a continuous (pore-free) graphene source electrode is attributed
      to modulation of the contact barrier height between the graphene and organic
      semiconductor due to a gate field induced Fermi level shift in the low density of
      electronic-states graphene electrode. Pores introduced in the graphene source
      electrode are shown to boost the G-VFET performance, which scales with the areal
      pore density taking advantage of both barrier height lowering and tunnel barrier
      thinning. Devices with areal pore densities of 20% exhibit on/off ratios and
      output current densities exceeding 10(6) and 200 mA/cm(2), respectively, at drain
      voltages below 5 V.

PMID- 23002808
TI  - Twenty-four-hour patterns in occurrence and pathophysiology of acute
      cardiovascular events and ischemic heart disease.
AB  - The scientific literature clearly establishes the occurrence of cardiovascular
      (CV) accidents and myocardial ischemic episodes is unevenly distributed during
      the 24 h. Such temporal patterns result from corresponding temporal variation in
      pathophysiologic mechanisms and cyclic environmental triggers that elicit the
      onset of clinical events. Moreover, both the pharmacokinetics and
      pharmacodynamics of many, though not all, CV medications have been shown to be
      influenced by the circadian time of their administration, even though further
      studies are necessary to better clarify the mechanisms of such influence on
      different drug classes, drug molecules, and pharmaceutical preparations. Twenty
      four-hour rhythmic organization of CV functions is such that defense mechanisms
      against acute events are incapable of providing the same degree of protection
      during the day and night. Instead, temporal gates of excessive susceptibility
      exist, particularly in the morning and to a lesser extent evening (in diurnally
      active persons), to aggressive mechanisms through which overt clinical
      manifestations may be triggered. When peak levels of critical physiologic
      variables, such as blood pressure (BP), heart rate (HR), rate pressure product
      (systolic BP * HR, surrogate measure of myocardial oxygen demand), sympathetic
      activation, and plasma levels of endogenous vasoconstricting substances, are
      aligned together at the same circadian time, the risk of acute events becomes
      significantly elevated such that even relatively minor and usually harmless
      physical and mental stress and environmental phenomena can precipitate dramatic
      life-threatening clinical manifestations. Hence, the delivery of CV medications
      needs to be synchronized in time, i.e., circadian time, in proportion to need as
      determined by established temporal patterns in risk of CV events, and in a manner
      that averts or minimizes undesired side effects.

PMID- 23002807
TI  - Comparison of risk factors for gestational hypertension and preeclampsia in
      Japanese singleton pregnancies.
AB  - AIM: To demonstrate the difference between risk factors for gestational
      hypertension (GH) and preeclampsia (PE). MATERIAL AND METHODS: Using data from
      women with no essential hypertension and with singleton births between 2001 and
      2005 delivering after 22 weeks of gestation at 125 centers in Japan (Japan
      Perinatal Registry Network) (n =241 292), we compared risk factors for GH and PE.
      Odds ratios were calculated using multivariate logistic regression analyses.
      RESULTS: Of 241 292 women, 2808 (1.2%) developed GH and 6423 (2.7%) developed PE.
      Thirty-five years or older, primiparity, diabetes mellitus, and renal disease
      increased the risk of both hypertensive conditions. Forty years or older was a
      risk factor only for GH, while primiparity, female baby, and renal disease were
      risk factors only for PE. Early-onset was a common risk factor for small-for
      gestational-age (SGA) in GH and PE, but in late-onset only PE was a risk factor
      for SGA. The main population of SGA infants was composed of PE cases because PE
      accounted for 83.3% of early-onset type before 32 weeks. Girl preponderance in
      the PE women was observed (sex ratio: boys/girls=0.904), while slight boy
      preponderance was seen in normotensive women (1.06) and GH (1.02). CONCLUSION:
      Preeclampsia is associated with lower fetal sex ratio (girl preponderance)
      compared to GH or normotensive. Presence of hypertension is a risk factor for SGA
      in early-onset GH and PE, and hypertension and proteinuria are risk factors for
      SGA in late-onset group.

PMID- 23002809
TI  - A longitudinal study of school belonging and academic motivation across high
      school.
AB  - This longitudinal study examined how school belonging changes over the years of
      high school, and how it is associated with academic achievement and motivation.
      Students from Latin American, Asian, and European backgrounds participated (N =
      572; age span = 13.94-19.15 years). In ninth grade, girls' school belonging was
      higher than boys'. Over the course of high school, however, girls' school
      belonging declined, whereas boys' remained stable. Within-person longitudinal
      analyses indicated that years in which students had higher school belonging were
      also years in which they felt that school was more enjoyable and more useful,
      above and beyond their actual level of achievement. Results highlight the
      importance of belonging for maintaining students' academic engagement during the
      teenage years.

PMID- 23002810
TI  - Sulfidization of Au(111) from thioacetic acid: an experimental and theoretical
      study.
AB  - We have studied the adsorption of thioacetic acid (TAAH) on Au(111) from solution
      deposition. The close proximity of the SH groups to CO groups makes this molecule
      very attractive for exploring the effect of the functional group on the stability
      of the S-C and S-Au bonds. Although thioacetic acid was supposed to decompose
      slowly in water by hydrolysis supplying hydrogen sulfide, this behavior is not
      expected in nonpolar solvents such as toluene or hexane. Therefore, we have used
      these solvents for TAAH self-assembly on the Au(111) surface. The
      characterization of the adsorbates has been done by electrochemical techniques, X
      ray photoelectron spectroscopy (XPS), and scanning tunneling microscopy (STM). We
      have found that even in nonpolar solvents thioacetic acid decomposes to S. The
      results have been discussed on the basis that the adsorbed species suffer a
      cleavage on the Au surface, leaving the S attached to it. The dissociation is a
      spontaneous process that reaches the final state very fast once it is
      energetically favorable, as can be interpreted from DFT calculations. The
      thioacetic acid adsorption reveals the strong effect that produces a functional
      group and the key role of the S-H bond cleavage in the self-assembly process.

PMID- 23002812
TI  - Collaboration among nurse practitioners and registered nurses in outpatient
      oncology settings in Canada.
AB  - AIM: This article is a report on a case study that described and analysed the
      collaborative process among nurse practitioners and registered nurses in oncology
      outpatient settings to understand and improve collaborative practice among
      nurses. BACKGROUND: Changes in the health system have created new models of care
      delivery, such as collaborative nursing teams. This has resulted in the increased
      opportunity for enhanced collaboration among nurse practitioners and registered
      nurses. The study was guided by Corser's Model of Collaborative Nurse-Physician
      Interactions (1998). DESIGN: Embedded single case design with multiple units of
      analysis. METHODS: Qualitative data were collected in 2010 using direct
      participant observations and individual and joint (nurse dyads) interviews in
      four outpatient oncology settings at one hospital in Ontario, Canada. FINDINGS:
      Thematic analysis revealed four themes: (1) Together Time Fosters Collaboration;
      (2) Basic Skills: The Brickworks of Collaboration; (3) Road Blocks: Obstacles to
      Collaboration; and (4) Nurses' Attitudes towards their Collaborative Work.
      CONCLUSION: Collaboration is a complex process that does not occur spontaneously.
      Collaboration requires nurses to not only work together but also spend time
      socially interacting away from the clinical setting. While nurses possess the
      conceptual knowledge of the meaning of collaboration, findings from this study
      showed that nurses struggle to understand how to collaborate in the practice
      setting. Strategies for improving nurse-nurse practitioner collaboration should
      include: the support and promotion of collaborative practice among nurses by
      hospital leadership and the development of institutional and organizational
      education programmes that would focus on creating innovative opportunities for
      nurses to learn about intraprofessional collaboration in the practice setting.

PMID- 23002813
TI  - Sharp tunneling peaks in a parametric oscillator: quantum resonances missing in
      the rotating wave approximation.
AB  - We describe a new mechanism of tunneling between period-two vibrational states of
      a weakly nonlinear, parametrically modulated oscillator. The tunneling results
      from resonant transitions induced by the fast oscillating terms conventionally
      disregarded in the rotating wave approximation (RWA). The tunneling amplitude
      displays resonant peaks as a function of the modulation frequency; near the
      maxima it is exponentially larger than the RWA tunneling amplitude.

PMID- 23002811
TI  - Exercise training-enhanced, endothelium-dependent dilation mediated by altered
      regulation of BK(Ca) channels in collateral-dependent porcine coronary
      arterioles.
AB  - OBJECTIVE: Test the hypothesis that exercise training increases the contribution
      of BK(Ca) channels to endothelium-mediated dilation in coronary arterioles from
      collateral-dependent myocardial regions of chronically occluded pig hearts and
      may function downstream of H2O2. METHODS: An ameroid constrictor was placed
      around the proximal left circumflex coronary artery to induce gradual occlusion
      in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly
      assigned to sedentary or exercise training (treadmill; 14 week) regimens.
      RESULTS: Exercise training significantly enhanced bradykinin-mediated dilation in
      collateral-dependent arterioles (~125 MUm diameter) compared with sedentary pigs.
      The BK(Ca) -channel blocker, iberiotoxin alone or in combination with the H2O2
      scavenger, polyethylene glycol catalase, reversed exercise training-enhanced
      dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K+
      currents (i.e., BK(Ca)-channel currents) were not different between smooth muscle
      cells of nonoccluded and collateral-dependent arterioles of sedentary and
      exercise trained groups. CONCLUSIONS: These data provide evidence that BK(Ca)
      channel activity contributes to exercise training-enhanced endothelium-dependent
      dilation in collateral-dependent coronary arterioles despite no change in smooth
      muscle BK(Ca)-channel current. Taken together, our findings suggest that a
      component of the bradykinin signaling pathway, which stimulates BK(Ca) channels,
      is enhanced by exercise training in collateral-dependent arterioles and suggest a
      potential role for H2O2 as the mediator.

PMID- 23002814
TI  - Disentanglement versus decoherence of two qubits in thermal noise.
AB  - We show that the influence of thermal noise, simulated by a 2D ferromagnetic
      Ising spin lattice on a pair of noninteracting, initially entangled qubits,
      represented by quantum spins, leads to unexpected evolution of quantum
      correlations. The high temperature noise leads to ultraslow decay of the quantum
      correlations. Decreasing the noise temperature we observe a decrease of the
      characteristic decay time scale. When the noise originates from a critical state,
      a revival of the quantum correlations is observed. This revival becomes
      oscillatory with a slowly decaying amplitude when the temperature is decreased
      below the critical region, leading to persistence of the quantum correlations.

PMID- 23002815
TI  - Deriving quantum theory from its local structure and reversibility.
AB  - We investigate the class of physical theories with the same local structure as
      quantum theory but potentially different global structure. It has previously been
      shown that any bipartite correlations generated by such a theory can be simulated
      in quantum theory but that this does not hold for tripartite correlations. Here
      we explore whether imposing an additional constraint on this space of theories
      that of dynamical reversibility-will allow us to recover the global quantum
      structure. In the particular case in which the local systems are identical
      qubits, we show that any theory admitting at least one continuous reversible
      interaction must be identical to quantum theory.

PMID- 23002816
TI  - PT-symmetric quantum Liouvillean dynamics.
AB  - We discuss a combination of unitary and antiunitary symmetry of quantum
      Liouvillean dynamics, in the context of open quantum systems, which implies a D2
      symmetry of the complex Liouvillean spectrum. For sufficiently weak system-bath
      coupling, it implies a uniform decay rate for all coherences, i.e., off-diagonal
      elements of the system's density matrix taken in the eigenbasis of the
      Hamiltonian. As an example, we discuss symmetrically boundary driven open XXZ
      spin 1/2 chains.

PMID- 23002818
TI  - Diffuse Galactic gamma rays from shock-accelerated cosmic rays.
AB  - A shock-accelerated particle flux is proportional to p(-s), where p is the
      particle momentum, follows from simple theoretical considerations of cosmic-ray
      acceleration at nonrelativistic shocks followed by rigidity-dependent escape into
      the Galactic halo. A flux of shock-accelerated cosmic-ray protons with s~2.8
      provides an adequate fit to the Fermi Large Area Telescope gamma-ray emission
      spectra of high-latitude and molecular cloud gas when uncertainties in nuclear
      production models are considered. A break in the spectrum of cosmic-ray protons
      claimed by Neronov, Semikoz, and Taylor [Phys. Rev. Lett. 108, 051105 (2012)]
      when fitting the gamma-ray spectra of high-latitude molecular clouds is a
      consequence of using a cosmic-ray proton flux described by a power law in kinetic
      energy.

PMID- 23002817
TI  - Quantum bath refrigeration towards absolute zero: challenging the unattainability
      principle.
AB  - A minimal model of a quantum refrigerator, i.e., a periodically phase-flipped two
      level system permanently coupled to a finite-capacity bath (cold bath) and an
      infinite heat dump (hot bath), is introduced and used to investigate the cooling
      of the cold bath towards absolute zero (T=0). Remarkably, the temperature scaling
      of the cold-bath cooling rate reveals that it does not vanish as T->0 for certain
      realistic quantized baths, e.g., phonons in strongly disordered media (fractons)
      or quantized spin waves in ferromagnets (magnons). This result challenges
      Nernst's third-law formulation known as the unattainability principle.

PMID- 23002819
TI  - Hawking radiation and nonequilibrium quantum critical current noise.
AB  - The dynamical scaling of quantum critical systems in thermal equilibrium may be
      inherited in the driven steady state, leading to universal out-of-equilibrium
      behavior. This attractive notion has been demonstrated in just a few cases. We
      demonstrate how holography-a mapping between the quantum critical system and a
      gravity dual-provides an illuminating perspective and new results. Nontrivial out
      of-equilibrium universality is particularly apparent in current noise, which is
      dual to Hawking radiation in the gravitational system. We calculate this in a two
      dimensional system driven by a strong in-plane electric field and deduce a
      universal scaling function interpolating between previously established
      equilibrium and far-from-equilibrium current noise. Since this applies at all
      fields, out-of-equilibrium experiments no longer require very high fields for
      comparison with theory.

PMID- 23002820
TI  - Emergent 3-manifolds from four dimensional superconformal indices.
AB  - We show that the smooth geometry of a hyperbolic 3-manifold emerges from a
      classical spin system defined on a 2D discrete lattice, and moreover, show that
      the process of this "dimensional oxidation" is equivalent with the dimensional
      reduction of a supersymmetric gauge theory from 4D to 3D. More concretely, we
      propose an equality between (1) the 4D superconformal index of a 4D N=1
      superconformal quiver gauge theory described by a bipartite graph on T(2) and (2)
      the partition function of a classical integrable spin chain on T(2). The 2D spin
      system is lifted to a hyperbolic 3-manifold after the dimensional reduction and
      using the Higgs mechanism in the 4D gauge theory.

PMID- 23002821
TI  - Anomalous chiral Fermi surfaces.
AB  - We provide a geometrical argument for the emergence of a Wess-Zumino-Witten (WZW)
      term in a Fermi surface threaded by a Berry curvature. In the presence of
      external fields, the gauged WZW term yields a chiral (triangle) anomaly for the
      fermionic current at the edge of the Fermi surface. The fermion number is
      conserved, though, since Berry curvatures always occur in pairs with opposite
      (monopole) charge. The anomalous vector and axial currents for a fermionic fluid
      at low temperature threaded by pairs of Berry curvatures are discussed. The
      leading temperature correction to the chiral vortical effect in a slowly rotating
      Fermi surface threaded by a Berry curvature may be tied to the gravitational
      anomaly.

PMID- 23002822
TI  - Neutrino mass hierarchy and octant determination with atmospheric neutrinos.
AB  - The recent discovery by the Daya-Bay and RENO experiments, that theta(13) is
      nonzero and relatively large, significantly impacts existing experiments and the
      planning of future facilities. In many scenarios, the nonzero value of theta(13)
      implies that theta(23) is likely to be different from pi/4. Additionally, large
      detectors will be sensitive to matter effects on the oscillations of atmospheric
      neutrinos, making it possible to determine the neutrino mass hierarchy and the
      octant of theta(23). We show that a 50 kT magnetized liquid argon neutrino
      detector can ascertain the mass hierarchy with a significance larger than 4sigma
      with moderate exposure times, and the octant at the level of 2-3sigma with
      greater exposure.

PMID- 23002823
TI  - Extracting B->K* form factors from data.
AB  - We extract ratios of B->K* form factors at low hadronic recoil from recent data
      on B->K*MU(+)MU(-) decays in a model independent way. The presented method will
      improve in the future with further (angular) studies in semileptonic rare B
      decays and advance our understanding of form factors, which are important inputs
      in precision tests of the standard model.

PMID- 23002824
TI  - B-L violating proton decay modes and new baryogenesis scenario in SO(10).
AB  - We show that grand unified theories based on SO(10) generate quite naturally
      baryon number violating dimension seven operators that violate B-L, and lead to
      novel nucleon decay modes such as n->e(-)K(+), e(-)pi(+) and p->nupi(+). We find
      that in two-step breaking schemes of nonsupersymmetric SO(10), the partial
      lifetimes for these modes can be within reach of experiments. The interactions
      responsible for these decay modes also provide a new way to understand the origin
      of matter in the Universe via the decays of grand unified theory (GUT) scale
      scalar bosons of SO(10). Their (B-L)-violating nature guarantees that the GUT
      scale induced baryon asymmetry is not washed out by the electroweak sphaleron
      interactions. In minimal SO(10) models this asymmetry is closely tied to the
      masses of quarks, leptons and the neutrinos.

PMID- 23002825
TI  - Precision jet substructure from boosted event shapes.
AB  - Jet substructure has emerged as a critical tool for LHC searches, but studies so
      far have relied heavily on shower Monte Carlo simulations, which formally
      approximate QCD at the leading-log level. We demonstrate that systematic higher
      order QCD computations of jet substructure can be carried out by boosting global
      event shapes by a large momentum Q and accounting for effects due to finite jet
      size, initial-state radiation (ISR), and the underlying event (UE) as 1/Q
      corrections. In particular, we compute the 2-subjettiness substructure
      distribution for boosted Z->qq[over -] events at the LHC at next-to-next-to-next
      to-leading-log order. The calculation is greatly simplified by recycling known
      results for the thrust distribution in e(+)e(-) collisions. The 2-subjettiness
      distribution quickly saturates, becoming Q independent for Q > or approximately
      equal to 400 GeV. Crucially, the effects of jet contamination from ISR/UE can be
      subtracted out analytically at large Q without knowing their detailed form.
      Amusingly, the Q=infinity and Q=0 distributions are related by a scaling by e up
      to next-to-leading-log order.

PMID- 23002826
TI  - Constraining the nuclear equation of state at subsaturation densities.
AB  - Only one-third of the nucleons in 208Pb occupy the saturation density area.
      Consequently, nuclear observables related to the average properties of nuclei,
      such as masses or radii, constrain the equation of state not at the saturation
      density but rather around the so-called crossing density, localized close to the
      mean value of the density of nuclei: rho is approximately equal to 0.11 fm(-3).
      This provides an explanation for the empirical fact that several equation of
      state quantities calculated with various functionals cross at a density
      significantly lower than the saturation one. The third derivative M of the energy
      per unit of volume at the crossing density is constrained by the giant monopole
      resonance measurements in an isotopic chain rather than the incompressibility at
      saturation density. The giant monopole resonance measurements provide M=1100+/-70
      MeV (6% uncertainty), whose extrapolation gives K(infinity)=230+/-40 MeV (17%
      uncertainty).

PMID- 23002827
TI  - Self-consistent calculations of the electric giant dipole resonances in light and
      heavy nuclei.
AB  - While bulk properties of stable nuclei are successfully reproduced by mean-field
      theories employing effective interactions, the dependence of the centroid energy
      of the electric giant dipole resonance on the nucleon number A is not. This
      problem is cured by considering many-particle correlations beyond mean-field
      theory, which we do within the quasiparticle time blocking approximation. The
      electric giant dipole resonances in 16O, 40Ca, and 208Pb are calculated using two
      new Skyrme interactions.

PMID- 23002828
TI  - Unveiling the intruder deformed 02(+) state in 34Si.
AB  - The 02(+) state in 34Si has been populated at the GANIL-LISE3 facility through
      the beta decay of a newly discovered 1(+) isomer in 34Al of 26(1) ms half-life.
      The simultaneous detection of e(+)e(-) pairs allowed the determination of the
      excitation energy E(02(+))=2719(3)  keV and the half-life T(1/2)=19.4(7) ns, from
      which an electric monopole strength of rho(2)(E0)=13.0(0.9)*10(-3) was deduced.
      The 2(1)(+) state is observed to decay both to the 0(1)(+) ground state and to
      the newly observed 0(2)(+) state [via a 607(2) keV transition] with a ratio
      R(2(1)(+)->0(1)(+)/2(1)(+)->0(2)(+))=1380(717). Gathering all information, a weak
      mixing with the 0(1)(+) and a large deformation parameter of beta=0.29(4) are
      found for the 0(2)(+) state, in good agreement with shell model calculations
      using a new SDPF-U-MIX interaction allowing np-nh excitations across the N=20
      shell gap.

PMID- 23002829
TI  - Coulomb energy difference as a probe of isospin-symmetry breaking in the upper f
      p-shell nuclei.
AB  - The anomaly in Coulomb energy differences (CEDs) between the isospin T=1 states
      in the odd-odd N=Z nucleus 70Br and the analogue states in its even-even partner
      70Se has remained a puzzle. This is a direct manifestation of isospin-symmetry
      breaking in effective nuclear interactions. Here, we perform large-scale shell
      model calculations for nuclei with A=66 to 78 using the new filter
      diagonalization method based on the Sakurai-Sugiura algorithm. The calculations
      reproduce well the experimental CED. The observed negative CED for A=70 are
      accounted for by the cross-shell neutron excitations from the fp shell to the
      g(9/2) intruder orbit with the enhanced electromagnetic spin-orbit contribution
      at this special nucleon number.

PMID- 23002830
TI  - Low yield of near-zero-momentum electrons and partial atomic stabilization in
      strong-field tunneling ionization.
AB  - We measure photoelectron angular distributions of single ionization of krypton
      and xenon atoms by laser pulses at 1320 nm, 0.2-1.0*10(14) W/cm(2), and observe
      that the yield of near-zero-momentum electrons in the strong-field tunneling
      ionization regime is significantly suppressed. Semiclassical simulations indicate
      that this local ionization suppression effect can be attributed to a fraction of
      the tunneled electrons that are released in a certain window of the initial field
      phase and transverse velocity are ejected into Rydberg elliptical orbits with a
      frequency much smaller than that of the laser; i.e., the corresponding atoms are
      stabilized. These electrons with high-lying atomic orbits are thus prevented from
      ionization, resulting in the substantially reduced near-zero-momentum electron
      yield. The refined transition between the Rydberg states of the stabilized atoms
      has implication on the THz radiation from gas targets in strong laser fields.

PMID- 23002831
TI  - Sub-binomial light.
AB  - The click statistics from on-off detector systems is quite different from the
      counting statistics of the more traditional detectors. This necessitates the
      introduction of new parameters to characterize the nonclassicality of fields from
      measurements using on-off detectors. To properly replace the Mandel Q(M)
      parameter, we introduce a parameter Q(B). A negative value represents a sub
      binomial statistics. This is possible only for quantum fields, even for super
      Poisson light. It eliminates the problems encountered in discerning
      nonclassicality using Mandel's Q(M) for on-off data.

PMID- 23002832
TI  - Experimental realization of light with time-separated correlations by rephasing
      amplified spontaneous emission.
AB  - Amplified spontaneous emission is a common noise source in active optical
      systems, it is generally seen as being an incoherent process. Here we excite an
      ensemble of rare earth ion dopants in a solid with a pi pulse, resulting in
      amplified spontaneous emission. The application of a second pi pulse leads to a
      coherent echo of the amplified spontaneous emission that is correlated in both
      amplitude and phase. For small optical thicknesses, we see evidence that the
      amplified spontaneous emission and its echo are entangled.

PMID- 23002833
TI  - Demonstration of photon-echo rephasing of spontaneous emission.
AB  - In this paper we report the first demonstration of "rephased amplified
      spontaneous emission" (RASE) with photon-counting detection. This protocol
      provides an all-in-one photon-pair source and quantum-memory that has
      applications as a quantum repeater node. The RASE protocol is temporally
      multimode, and in this demonstration the photon echo was generated in a way that
      is spatially multimode and includes intermediate storage between two potentially
      long-lived spin states. A correlation between spontaneous emission and its photon
      echo was observed, using an ensemble of Pr(3+) ions doped into a Y2SiO5 crystal.
      Alterations that would allow for the measurement of nonclassical correlations are
      identified. These should generally apply for future experiments in rare-earth ion
      crystals, which are promising systems for implementing highly-multiplexed quantum
      repeater operations.

PMID- 23002834
TI  - Observing superradiant decay of excited-state helium atoms inside helium plasma.
AB  - Using femtosecond transient absorption spectroscopy on excited-state helium atoms
      in a plasma created through optical field ionization, we measured the decay of
      2(3)S-2(3)P excitation with sub-ps temporal resolution. The population evolution
      shows that initial decay is significantly faster than the electron-atom
      collisions and three orders of magnitude faster than the single atom spontaneous
      decay rate. This indicates on superradiant coherent behavior of the atomic system
      inside the plasma.

PMID- 23002835
TI  - Blue self-frequency shift of slow solitons and radiation locking in a line-defect
      waveguide.
AB  - We investigate experimentally resonant radiation processes driven by slow
      solitons in a dispersion-engineered photonic crystal waveguide in a regime
      virtually free of dissipative nonlinear processes (two-photon absorption and
      Raman scattering). Strong (30% energy conversion) Cherenkov-like radiation
      accompanied by the blue self-frequency shift of the soliton is observed close to
      the zero dispersion point, and is explained in terms of the soliton-radiation
      locking of the velocity.

PMID- 23002836
TI  - Wide-field vibrational phase imaging.
AB  - We propose and implement a wide-field microscopy method to retrieve the real and
      imaginary part of a field emitted by coherent and resonant molecular scatterers.
      The technique is based on wave-front sensing and does not require the use of any
      reference beam. We exemplify its ability in wide-field coherent anti-Stokes Raman
      scattering imaging and retrieve the complex anti-Stokes field while spectrally
      scanning a molecular vibrational resonance. This approach gives access to the
      background-free Raman spectrum of the targeted molecular bond.

PMID- 23002837
TI  - Optical gap solitons and truncated nonlinear Bloch waves in temporal lattices.
AB  - We experimentally demonstrate the formation and stable propagation of various
      types of discrete temporal solitons in an optical fiber system. Pulses
      interacting with a time-periodic potential and defocusing nonlinearity are shown
      to form gap solitons and nonlinear truncated Bloch waves. Multi-pulse solitons
      with defects, as well as novel structures composed of a strong soliton riding on
      a weaker truncated nonlinear Bloch wave are shown to propagate over up to eleven
      coupling lengths. The nonlinear dynamics of all pulse structures is monitored
      over the full propagation distance which provides detailed insight into the
      soliton dynamics.

PMID- 23002838
TI  - Cosine-Gauss plasmon beam: a localized long-range nondiffracting surface wave.
AB  - A new surface wave is introduced, the cosine-Gauss beam, which does not diffract
      while it propagates in a straight line and tightly bound to the metallic surface
      for distances up to 80 MUm. The generation of this highly localized wave is shown
      to be straightforward and highly controllable, with varying degrees of transverse
      confinement and directionality, by fabricating a plasmon launcher consisting of
      intersecting metallic gratings. Cosine-Gauss beams have potential for
      applications in plasmonics, notably for efficient coupling to nanophotonic
      devices, opening up new design possibilities for next-generation optical
      interconnects.

PMID- 23002839
TI  - Gyroscopic destabilization of molecular rotation and quantum bifurcation observed
      in the structure of the nu23 fundamental of dimethylsulfoxyde.
AB  - Following the first successful high-resolution study of the "perpendicular" band
      of dimethylsulfoxyde at 324 cm(-1), associated with the nu23 bending vibration,
      we discovered a sequence of fourfold degenerate clusters of rotational levels at
      high angular momenta J>40. This unusual system of localized states corresponds to
      classical rotations about a pair of "tilted" axes, which become stationary at
      high J, after the principal axis of inertia A loses stability and bifurcates for
      J~27.

PMID- 23002840
TI  - Invariant beta ensembles and the Gauss-Wigner crossover.
AB  - We define a new diffusive matrix model converging toward the beta-Dyson Brownian
      motion for all beta is an element of [0,2] that provides an explicit construction
      of beta ensembles of random matrices that is invariant under the orthogonal or
      unitary group. For small values of beta, our process allows one to interpolate
      smoothly between the Gaussian distribution and the Wigner semicircle. The
      interpolating limit distributions form a one parameter family that can be
      explicitly computed. This also allows us to compute the finite-size corrections
      to the semicircle.

PMID- 23002841
TI  - Electrically tunable partial coalescence of oppositely charged drops.
AB  - We report the existence of a critical ionic conductivity below which oppositely
      charged drops only partially coalesce. The extent of coalescence between
      dissimilarly sized water drops in oil can be tuned from complete coalescence at
      low electric field strengths to complete noncoalescence at high field strengths,
      thus providing external control over the daughter droplet size. Strikingly, the
      size and charge of the daughter droplet are both independent of the ionic
      conductivity. We present evidence suggesting the charge transfer is instead
      strongly influenced by convection associated with the capillary-driven
      penetration of a vortex into the larger drop, and we demonstrate that the size of
      the daughter droplet is consistent with a scaling model based on a balance
      between capillary-driven inertia and electrostatic repulsion.

PMID- 23002842
TI  - Knudsen layer reduction of fusion reactivity.
AB  - Knudsen layer losses of tail fuel ions can significantly reduce the fusion
      reactivity of multi-keV DT in capsules with small fuel rhor; sizable yield
      reduction can result for small inertial confinement fusion (ICF) capsules. This
      effect is most pronounced when the distance from a burning DT gas region to a
      nonreacting or cold wall is comparable to the mean free path of reacting fuel
      ions. A simplified asymptotic theory of Knudsen layer tail depletion is presented
      and a nonlocal reduced fusion reactivity model is obtained. Application of the
      model in simulations of ICF capsule implosion experiments gives calculated yields
      and ion temperatures that are in much closer agreement with observations than are
      the results of "nominal" or mixed simulations omitting the model.

PMID- 23002843
TI  - Spin-orbit coupled degenerate Fermi gases.
AB  - In this Letter, we report the first experimental realization and investigation of
      a spin-orbit coupled Fermi gas. Both spin dephasing in spin dynamics and momentum
      distribution asymmetry of the equilibrium state are observed as hallmarks of spin
      orbit coupling in a Fermi gas. The single particle dispersion is mapped out by
      using momentum-resolved radio-frequency spectroscopy. From momentum distribution
      and momentum-resolved radio-frequency spectroscopy, we observe the change of
      fermion population in different helicity branches consistent with a finite
      temperature calculation, which indicates that a Lifshitz transition of the Fermi
      surface topology change can be found by further cooling the system.

PMID- 23002844
TI  - Spin-injection spectroscopy of a spin-orbit coupled Fermi gas.
AB  - The coupling of the spin of electrons to their motional state lies at the heart
      of recently discovered topological phases of matter. Here we create and detect
      spin-orbit coupling in an atomic Fermi gas, a highly controllable form of quantum
      degenerate matter. We directly reveal the spin-orbit gap via spin-injection
      spectroscopy, which characterizes the energy-momentum dispersion and spin
      composition of the quantum states. For energies within the spin-orbit gap, the
      system acts as a spin diode. We also create a spin-orbit coupled lattice and
      probe its spinful band structure, which features additional spin gaps and a fully
      gapped spectrum. In the presence of s-wave interactions, such systems should
      display induced p-wave pairing, topological superfluidity, and Majorana edge
      states.

PMID- 23002845
TI  - Relationship between equilibrium fluctuations and shear-coupled motion of grain
      boundaries.
AB  - We derive general analytical expressions relating the equilibrium fluctuations of
      a grain boundary to key parameters governing its motion coupled to shear
      deformation. We validate these expressions by molecular dynamics simulations for
      symmetrical tilt boundaries and demonstrate how they can be used to extract the
      misorientation dependence of the grain-boundary mobility. The results shed light
      on fundamental relationships between equilibrium and nonequilibrium grain
      boundary properties and provide new means to predict those properties.

PMID- 23002846
TI  - Pulsed ion beam measurement of the time constant of dynamic annealing in Si.
AB  - Under ion irradiation, all crystalline materials display some degree of dynamic
      annealing when defects experience evolution after the thermalization of collision
      cascades. The exact time scales of such defect relaxation processes are, however,
      unknown even for Si at room temperature. Here, we use a pulsed ion-beam method to
      measure a characteristic time constant of dominant dynamic annealing processes of
      about 6 ms in Si bombarded at room temperature with 500 keV Ar ions.

PMID- 23002847
TI  - Europium-IV: an incommensurately modulated crystal structure in the lanthanides.
AB  - High-resolution x-ray powder-diffraction experiments were performed on europium
      metal at high pressure up to 50 GPa. At variance with previous reports, the hcp
      phase of Eu was observed to be stable not only to 18 GPa, but to 31.5 GPa. At
      31.5(5) GPa, europium transforms to a phase (Eu-IV) with an incommensurately
      modulated monoclinic crystal structure with superspace group C2/c(q(1)0q(3))00.
      This new phase was observed to be stable to ~37.0 GPa, where another phase
      transition was observed. Eu-IV is the first phase in the lanthanide elements with
      an incommensurate crystal structure.

PMID- 23002848
TI  - Adsorbate transport on graphene by electromigration.
AB  - Chemical functionalization of graphene holds promise for various applications
      ranging from nanoelectronics to catalysis, drug delivery, and nanoassembly. In
      many applications it is important to be able to transport adsorbates on graphene
      in real time. We propose to use electromigration to drive the adsorbate transport
      across the graphene sheet. To assess the efficiency of electromigration, we
      develop a tight-binding model of electromigration of an adsorbate on graphene and
      obtain simple analytical expressions for different contributions to the
      electromigration force. Using experimentally accessible parameters of realistic
      graphene-based devices as well as electronic structure theory calculations to
      parametrize the developed model, we argue that electromigration on graphene can
      be efficient. As an example, we show that the drift velocity of atomic oxygen
      covalently bound to graphene can reach ~1 cm/s.

PMID- 23002849
TI  - Complete topology of cells, grains, and bubbles in three-dimensional
      microstructures.
AB  - We introduce a general, efficient method to completely describe the topology of
      individual grains, bubbles, and cells in three-dimensional polycrystals, foams,
      and other multicellular microstructures. This approach is applied to a pair of
      three-dimensional microstructures that are often regarded as close analogues in
      the literature: one resulting from normal grain growth (mean curvature flow) and
      another resulting from a random Poisson-Voronoi tessellation of space. Grain
      growth strongly favors particular grain topologies, compared with the Poisson
      Voronoi model. Moreover, the frequencies of highly symmetric grains are orders of
      magnitude higher in the grain growth microstructure than they are in the Poisson
      Voronoi one. Grain topology statistics provide a strong, robust differentiator of
      different cellular microstructures and provide hints to the processes that drive
      different classes of microstructure evolution.

PMID- 23002850
TI  - Electrostatic potentials at Cu(In,Ga)Se2 grain boundaries: experiment and
      simulations.
AB  - In the present Letter, we report on a combined ab initio density functional
      theory calculation, multislice simulation, and electron holography study,
      performed on a Sigma9 grain boundary (GB) in a CuGaSe2 bicrystal, which exhibits
      a lower symmetry compared with highly symmetric Sigma3 GBs. We find an
      electrostatic potential well at the Sigma9 GB of 0.8 V in depth and 1.3 nm in
      width, which in comparison with results from Sigma3 and random GBs exhibits the
      trend of increasing potential-well depths with lower symmetry. The presence of
      this potential well at the Sigma9 GB can be explained conclusively by a reduced
      density of atoms at the GB. Considering experimental limitations in resolution,
      we demonstrate quantitative agreement of experiment and theory.

PMID- 23002851
TI  - Statistics of dislocation slip avalanches in nanosized single crystals show tuned
      critical behavior predicted by a simple mean field model.
AB  - We show that slowly sheared metallic nanocrystals deform via discrete strain
      bursts (slips), whose size distributions follow power laws with stress-dependent
      cutoffs. We show for the first time that plasticity reflects tuned criticality,
      by collapsing the stress-dependent slip-size distributions onto a predicted
      scaling function. Both power-law exponents and scaling function agree with mean
      field theory predictions. Our study of 7 materials and 2 crystal structures, at
      various deformation rates, stresses, and crystal sizes down to 75 nm, attests to
      the universal characteristics of plasticity.

PMID- 23002852
TI  - Correlation between beta relaxation and self-diffusion of the smallest
      constituting atoms in metallic glasses.
AB  - In multicomponent metallic glasses, we demonstrate that diffusion and secondary
      (beta) relaxation are closely related. The diffusion motion of the smallest
      constituting atoms takes place within the temperature and time regimes where the
      beta relaxations are activated, and, in particular, the two processes have
      similar activation energies. We suggest cooperative stringlike atomic motion
      plays an important role in both processes. This finding provides additional
      insights into the structural origin of the beta relaxations as well as the
      mechanisms of diffusions in metallic glasses.

PMID- 23002853
TI  - Fluctuations and criticality of a granular solid-liquid-like phase transition.
AB  - We present an experimental study of density and order fluctuations in the
      vicinity of the solid-liquid-like transition that occurs in a vibrated quasi-two
      dimensional granular system. The two-dimensional projected static and dynamic
      correlation functions are studied. We show that density fluctuations,
      characterized through the structure factor, increase in size and intensity as the
      transition is approached, but they do not change significantly at the transition
      itself. The dense, metastable clusters, which present square symmetry, also
      increase their local order in the vicinity of the transition. This is
      characterized through the bond-orientational order parameter Q4, which in Fourier
      space shows an Ornstein-Zernike-like behavior. Depending on the filling density
      and vertical height, the transition can be of first- or second-order type. In the
      latter case, the associated correlation length xi4, the relaxation time tau4, the
      zero k limit of Q4 fluctuations (static susceptibility), the pair correlation
      function of Q4, and the amplitude of the order parameter obey critical power
      laws, with saturations due to finite size effects. Their respective critical
      exponents are nu(perpendicular))=1, nu(parallel)=2, gamma=1, eta=0.67, and
      beta=1/2, whereas the dynamical critical exponent
      z=nu(parallel)/nu(perpendicular)=2. These results are consistent with model C of
      dynamical critical phenomena, valid for a nonconserved critical order parameter
      (bond-orientation order) coupled to a conserved field (density).

PMID- 23002854
TI  - Homogeneous crystal nucleation near a metastable fluid-fluid phase transition.
AB  - Several scenarios exist for the protein crystallization and aggregation in
      solutions near a metastable fluid-fluid phase separation below the solubility
      line. Based on computations, it was proposed that the fluid-fluid critical point
      enhances the crystallization rate by many orders of magnitude, while, based on
      experiments, it was proposed that the fluid-fluid spinodal controls the
      crystallization rate. Using molecular dynamic simulations for an isotropic model
      with sticky interaction, we show that neither of these scenarios adequately
      describes the crystallization mechanism near a metastable fluid-fluid phase
      separation. We find that the emergence of the high-density fluid inside the
      spinodal drastically enhances the crystal nucleation in the subcritical region
      following Ostwald's rule of stages.

PMID- 23002855
TI  - Soft-sphere packings at finite pressure but unstable to shear.
AB  - When are athermal soft-sphere packings jammed? Any experimentally relevant
      definition must, at the very least, require a jammed packing to resist shear. We
      demonstrate that widely used (numerical) protocols, in which particles are
      compressed together, can and do produce packings that are unstable to shear-and
      that the probability of generating such packings reaches one near jamming. We
      introduce a new protocol which, by allowing the system to explore different box
      shapes as it equilibrates, generates truly jammed packings with strictly positive
      shear moduli G. For these packings, the scaling of the average of G is consistent
      with earlier results, while the probability distribution P(G) exhibits novel and
      rich scalings.

PMID- 23002856
TI  - Finite-size scaling at the jamming transition.
AB  - We present an analysis of finite-size effects in jammed packings of N soft,
      frictionless spheres at zero temperature. There is a 1/N correction to the
      discrete jump in the contact number at the transition so that jammed packings
      exist only above isostaticity. As a result, the canonical power-law scalings of
      the contact number and elastic moduli break down at low pressure. These
      quantities exhibit scaling collapse with a nontrivial scaling function,
      demonstrating that the jamming transition can be considered a phase transition.
      Scaling is achieved as a function of N in both two and three dimensions,
      indicating an upper critical dimension of 2.

PMID- 23002857
TI  - Adam-Gibbs relation for glass-forming liquids in two, three, and four dimensions.
AB  - The Adam-Gibbs relation between relaxation times and the configurational entropy
      has been tested extensively for glass formers using experimental data and
      computer simulation results. Although the form of the relation contains no
      dependence on the spatial dimensionality in the original formulation, subsequent
      derivations of the Adam-Gibbs relation allow for such a possibility. We test the
      Adam-Gibbs relation in two, three, and four spatial dimensions using computer
      simulations of model glass formers. We find that the relation is valid in three
      and four dimensions. But in two dimensions, the relation does not hold, and
      interestingly, no single alternate relation describes the results for the
      different model systems we study.

PMID- 23002858
TI  - Thermal conductivity and large isotope effect in GaN from first principles.
AB  - We present atomistic first principles results for the lattice thermal
      conductivity of GaN and compare them to those for GaP, GaAs, and GaSb. In GaN we
      find a large increase to the thermal conductivity with isotopic enrichment, ~65%
      at room temperature. We show that both the high thermal conductivity and its
      enhancement with isotopic enrichment in GaN arise from the weak coupling of heat
      carrying acoustic phonons with optic phonons. This weak scattering results from
      stiff atomic bonds and the large Ga to N mass ratio, which give phonons high
      frequencies and also a pronounced energy gap between acoustic and optic phonons
      compared to other materials. Rigorous understanding of these features in GaN
      gives important insights into the interplay between intrinsic phonon-phonon
      scattering and isotopic scattering in a range of materials.

PMID- 23002859
TI  - Cooperative mercury motion in the ionic conductor Cu2HgI4.
AB  - We present the observation of glasslike dynamic correlations of mobile mercury
      ions in the ionic conductor Cu2HgI4, detected in both NMR and nonlinear
      conductivity experiments. The results show that dynamic cooperativity appears in
      systems seemingly unrelated to glassy and soft arrested materials. A simple
      kinetic two-component model is proposed, which seems to provide a good
      description of the cooperative ionic dynamics.

PMID- 23002860
TI  - Coarsening scenarios in unstable crystal growth.
AB  - Crystal surfaces may undergo thermodynamical as well as kinetic, out-of
      equilibrium instabilities. We consider the case of mound and pyramid formation, a
      common phenomenon in crystal growth and a long-standing problem in the field of
      pattern formation and coarsening dynamics. We are finally able to attack the
      problem analytically and get rigorous results. Three dynamical scenarios are
      possible: perpetual coarsening, interrupted coarsening, and no coarsening. In the
      perpetual coarsening scenario, mound size increases in time as L~t(n), where the
      coarsening exponent is n=1/3 when faceting occurs, otherwise n=1/4.

PMID- 23002861
TI  - Long-range, photon-mediated exciton hybridization in an all-organic, one
      dimensional photonic crystal.
AB  - We demonstrate an all-organic, one-dimensional photonic crystal tuned to the
      regime of strong exciton-photon coupling. The structure consists of a high index
      of refraction light-absorbing active layer periodically distributed in a low
      index of refraction nonabsorbing background medium. The strongly coupled state in
      this structure is shared between multiple active layers separated by distances
      longer than the wavelength of light in the structure. In order to investigate the
      potential for long-range energy transfer, photon-mediated exciton hybridization
      is demonstrated between multiple absorbing species spatially separated in the
      photonic crystal.

PMID- 23002862
TI  - Unconventional Hall effect in pnictides from interband interactions.
AB  - We calculate the Hall transport in a multiband system with a dominant interband
      interaction between carriers having electron and hole character. We show that
      this situation gives rise to an unconventional scenario, beyond the Boltzmann
      theory, where the quasiparticle currents dressed by vertex corrections acquire
      the character of the majority carriers. This leads to a larger (positive or
      negative) Hall coefficient than what may be expected on the basis of the carrier
      balance, with a marked temperature dependence. Our results explain the puzzling
      measurements in pnictides and provide a more general framework for transport
      properties in multiband materials.

PMID- 23002863
TI  - Interacting one-dimensional fermionic symmetry-protected topological phases.
AB  - In free fermion systems with given symmetry and dimension, the possible
      topological phases are labeled by elements of only three types of Abelian groups,
      0, Z2, or Z. For example, noninteracting one-dimensional fermionic
      superconducting phases with S(z) spin rotation and time-reversal symmetries are
      classified by Z. We show that with weak interactions, this classification reduces
      to Z4. Using group cohomology, one can additionally show that there are only four
      distinct phases for such one-dimensional superconductors even with strong
      interactions. Comparing their projective representations, we find that all these
      four symmetry-protected topological phases can be realized with free fermions.
      Further, we show that one-dimensional fermionic superconducting phases with Z(n)
      discrete S(z) spin rotation and time-reversal symmetries are classified by Z4
      when n is even and Z2 when n is odd; again, all these strongly interacting
      topological phases can be realized by noninteracting fermions. Our approach can
      be applied to systems with other symmetries to see which one-dimensional
      topological phases can be realized with free fermions.

PMID- 23002864
TI  - Flat-band ferromagnetism as a Pauli-correlated percolation problem.
AB  - We investigate the location and nature of the para-ferro transition of
      interacting electrons in dispersionless bands using the example of the Hubbard
      model on the Tasaki lattice. This case can be analyzed as a geometric site
      percolation problem where different configurations appear with nontrivial
      weights. We provide a complete exact solution for the one-dimensional case and
      develop a numerical algorithm for the two-dimensional case. In two dimensions the
      paramagnetic phase persists beyond the uncorrelated percolation point, and the
      grand-canonical transition is via a first-order jump to an unsaturated
      ferromagnetic phase.

PMID- 23002865
TI  - Critical behavior of a strongly interacting 2D electron system.
AB  - With decreasing density n(s) the thermopower S of a low-disorder two-dimensional
      electron system in silicon is found to exhibit a sharp increase by more than an
      order of magnitude tending to a divergence at a finite disorder-independent
      density n(t) consistent with the critical form (-T/S) is proportional to (n(s)
      n(t))(x) with x=1.0+/-0.1 (T is the temperature). Our results provide clear
      evidence for an interaction-induced transition to a new phase at low density in a
      strongly interacting 2D electron system.

PMID- 23002866
TI  - Limit cycle and anomalous capacitance in the Kondo insulator SmB6.
AB  - We report a frequency coding limit cycle and anomalous capacitance in the Kondo
      insulator SmB6 at low temperatures where the insulating gap becomes fully opened.
      The limit cycle appears to be associated with local activity and autocatalytic
      temporal pattern formation, as occurs in biological systems. The measured
      anomalous capacitance may indicate surface and bulk separation, suggesting the
      formation of a surface conducting state. The biological analogy suggests lossless
      information transport and complex information coding, and the surface state with
      a superconductor would provide a possible venue for quantum computing resources
      without decoherence.

PMID- 23002867
TI  - Current-induced switching of perpendicularly magnetized magnetic layers using
      spin torque from the spin Hall effect.
AB  - We show that in a perpendicularly magnetized Pt/Co bilayer the spin-Hall effect
      (SHE) in Pt can produce a spin torque strong enough to efficiently rotate and
      switch the Co magnetization. We calculate the phase diagram of switching driven
      by this torque, finding quantitative agreement with experiments. When optimized,
      the SHE torque can enable memory and logic devices with similar critical currents
      and improved reliability compared to conventional spin-torque switching. We
      suggest that the SHE torque also affects current-driven magnetic domain wall
      motion in Pt/ferromagnet bilayers.

PMID- 23002868
TI  - Magnon mediated electric current drag across a ferromagnetic insulator layer.
AB  - In a semiconductor heterostructure, the Coulomb interaction is responsible for
      the electric current drag between two 2D electron gases across an electron
      impenetrable insulator. For two metallic layers separated by a ferromagnetic
      insulator (FI) layer, the electric current drag can be mediated by a
      nonequilibrium magnon current of the FI. We determine the drag current by using
      the semiclassical Boltzmann approach with proper boundary conditions of electrons
      and magnons at the metal-FI interface.

PMID- 23002869
TI  - Universal conductance fluctuations in Dirac materials in the presence of long
      range disorder.
AB  - We study quantum transport in Dirac materials with a single fermionic Dirac cone
      (strong topological insulators and graphene in the absence of intervalley
      coupling) in the presence of non-Gaussian long-range disorder. We show, by
      directly calculating numerically the conductance fluctuations, that in the limit
      of very large system size and disorder strength, quantum transport becomes
      universal. However, a systematic deviation away from universality is obtained for
      realistic system parameters. By comparing our results to existing experimental
      data on 1/f noise, we suggest that many of the graphene samples studied to date
      are in a nonuniversal crossover regime of conductance fluctuations.

PMID- 23002870
TI  - Topological insulating in GeTe/Sb2Te3 phase-change superlattice.
AB  - GeTe/Sb2Te3 superlattice phase-change memory devices demonstrated greatly
      improved performance over that of Ge2Sb2Te5, a prototype record media for phase
      change random access memory. In this work, we show that this type of GeTe/Sb2Te3
      superlattice exhibits topological insulating behavior on the basis of ab initio
      calculations. The analysis of the band structures and parities as well as Z2
      topological invariants unravels the topological insulating nature in these
      artificial materials. Furthermore, the topological insulating character remains
      in the GeTe/Sb2Te3 superlattice under small compressive strains, whereas it is
      not observed as more Sb2Te3 building blocks introduced in the superlattice. The
      present results show that multifunctional data storages may be achieved in the
      GeTe/Sb2Te3 superlattice. Such kinds of artificial materials can be used in phase
      change random access memory, spintronics, and quantum computing.

PMID- 23002871
TI  - Giant ambipolar Rashba effect in the semiconductor BiTeI.
AB  - We observe a giant spin-orbit splitting in the bulk and surface states of the
      noncentrosymmetric semiconductor BiTeI. We show that the Fermi level can be
      placed in the valence or in the conduction band by controlling the surface
      termination. In both cases, it intersects spin-polarized bands, in the
      corresponding surface depletion and accumulation layers. The momentum splitting
      of these bands is not affected by adsorbate-induced changes in the surface
      potential. These findings demonstrate that two properties crucial for enabling
      semiconductor-based spin electronics-a large, robust spin splitting and ambipolar
      conduction-are present in this material.

PMID- 23002872
TI  - Nonunitary triplet pairing in the centrosymmetric superconductor LaNiGa2.
AB  - Muon spin rotation and relaxation experiments on the centrosymmetric
      intermetallic superconductor LaNiGa2 are reported. The appearance of spontaneous
      magnetic fields coincides with the onset of superconductivity, implying that the
      superconducting state breaks time reversal symmetry, similarly to
      noncentrosymmetric LaNiC2. Only four triplet states are compatible with this
      observation, all of which are nonunitary triplets. This suggests that LaNiGa2 is
      the centrosymmetric analogue of LaNiC2. We argue that these materials are
      representatives of a new family of paramagnetic nonunitary superconductors.

PMID- 23002873
TI  - Giant phonon softening and enhancement of superconductivity by phosphorus doping
      of BaNi2As2.
AB  - The effects of phosphorus doping on the structural and superconducting phase
      transitions of BaNi2(As(1-x)P(x))2 were studied. The specific heat, resistivity,
      and magnetic susceptibility were measured. The results revealed an abrupt
      increase in the superconducting transition temperature (T(c)) from 0.6 K in the
      triclinic phase (space group P1-) with less phosphorus (x<=0.067) to 3.3 K in the
      tetragonal phase (space group I4/mmm) with more phosphorus (x>=0.067). Our data
      analysis suggests that a doping-induced softening related to an in-plane Ni and
      As(P) phonon mode is responsible for the enhanced superconductivity in the
      tetragonal phase.

PMID- 23002874
TI  - Lifetime of gapped excitations in a collinear quantum antiferromagnet.
AB  - We demonstrate that local modulations of magnetic couplings have a profound
      effect on the temperature dependence of the relaxation rate of optical magnons in
      a wide class of antiferromagnets in which gapped excitations coexist with
      acoustic spin waves. In a two-dimensional collinear antiferromagnet with an easy
      plane anisotropy, the disorder-induced relaxation rate of the gapped mode,
      Gamma(imp)~Gamma(0)+A(TlnT)2, greatly exceeds the magnon-magnon damping, Gamma(m
      m)~BT5, negligible at low temperatures. We measure the lifetime of gapped magnons
      in a prototype XY antiferromagnet BaNi2(PO4)2 using a high-resolution neutron
      resonance spin-echo technique and find experimental data in close accord with the
      theoretical prediction. Similarly strong effects of disorder in the three
      dimensional case and in noncollinear antiferromagnets are discussed.

PMID- 23002875
TI  - Surface roughness dominated pinning mechanism of magnetic vortices in soft
      ferromagnetic films.
AB  - Although pinning of domain walls in ferromagnets is ubiquitous, the absence of an
      appropriate characterization tool has limited the ability to correlate the
      physical and magnetic microstructures of ferromagnetic films with specific
      pinning mechanisms. Here, we show that the pinning of a magnetic vortex, the
      simplest possible domain structure in soft ferromagnets, is strongly correlated
      with surface roughness, and we make a quantitative comparison of the pinning
      energy and spatial range in films of various thickness. The results demonstrate
      that thickness fluctuations on the lateral length scale of the vortex core
      diameter, i.e., an effective roughness at a specific length scale, provides the
      dominant pinning mechanism. We argue that this mechanism will be important in
      virtually any soft ferromagnetic film.

PMID- 23002876
TI  - Spiral-spin-driven ferroelectricity in a multiferroic delafossite AgFeO2.
AB  - We have performed dielectric measurements and neutron diffraction experiments on
      the delafossite AgFeO2. A ferroelectric polarization P is approximately equal to
      300 MUC/m2 was observed in a powder sample, below 9 K. The neutron diffraction
      experiment demonstrated successive magnetostructural phase transitions at
      T(N1)=15 K and T(N2)=9 K. The magnetic structure for 9 K<=T<=15 K is a spin
      density wave with a temperature dependent incommensurate modulation k=(-1, q,
      1/2), q is approximately equal to 0.384. Below 9 K, the magnetic structure turns
      into elliptical cycloid with the incommensurate propagation vector k=(
      1/2,q,1/2), q is approximately equal to 0.2026 Based on the deduced magnetic
      point-group symmetry m1' of the low-temperature polar phase, we conclude that the
      ferroelectric polarization in AgFeO2 is perpendicular to the monoclinic b axis
      and is driven by the inverse Dzyaloshinskii-Moriya effect with two orthogonal
      components p1 is proportional to r(ij)*(S(i)*S(j)) and p2 is proportional to
      S(i)*S(j).

PMID- 23002877
TI  - Core-core dynamics in spin vortex pairs.
AB  - We investigate nanopillars in which two thin ferromagnetic particles are
      separated by a nanometer thin nonmagnetic spacer and can be set into stable spin
      vortex-pair configurations. We find that the previously unexplored limit of
      strong vortex core-core coupling can dominate the spin dynamics in the system. We
      observe experimentally and explain analytically and numerically how the 0.2 GHz
      gyrational resonance modes of the individual vortices are transformed into a 2
      GHz collective rotational resonance mode in the configurations where the two
      cores form a bound pair.

PMID- 23002878
TI  - Vindication of Yb2Ti2O7 as a model exchange quantum spin ice.
AB  - We use numerical linked-cluster expansions to compute the specific heat C(T) and
      entropy S(T) of a quantum spin ice Hamiltonian for Yb2Ti2O7 using anisotropic
      exchange interactions, recently determined from inelastic neutron scattering
      measurements, and find good agreement with experimental calorimetric data. This
      vindicates Yb2Ti2O7 as a model quantum spin ice. We find that in the perturbative
      weak quantum regime, such a system has a ferrimagnetic ordered ground state, with
      two peaks in C(T): a Schottky anomaly signaling the paramagnetic to spin ice
      crossover, followed at a lower temperature by a sharp peak accompanying a first
      order phase transition to the ordered state. We suggest that the two C(T)
      features observed in Yb2Ti2O7 are associated with the same physics. Spin
      excitations in this regime consist of weakly confined spinon-antispinon pairs. We
      anticipate that the conventional ground state with exotic quantum dynamics will
      prove a prevalent characteristic of many real quantum spin ice materials.

PMID- 23002879
TI  - Geometrical frustration in the spin liquid beta'-Me3EtSb[Pd(dmit)2]2 and the
      valence-bond solid Me3EtP[Pd(dmit)2]2.
AB  - We show that the electronic structures of the title compounds predicted by
      density functional theory are well described by tight binding models. We
      determine the frustration ratio, J'/J, of the Heisenberg model on the anisotropic
      triangular lattice, which describes the spin degrees of freedom in the Mott
      insulating phase for a range of Pd(dmit)2 salts. All of the antiferromagnetic
      materials studied have J'/J is < or approximately equal to 0.5 or J'/J > or
      approximately equal to 0.9, and all salts with 0.5 < or approximately equal to
      J'/J < or approximately equal to 0.9 are known, experimentally, to be charge
      ordered valence-bond solids or spin liquids.

PMID- 23002880
TI  - Measurement of the four-point susceptibility of an out-of-equilibrium colloidal
      solution of nanoparticles using time-resolved light scattering.
AB  - The spatial fluctuations of the dynamics of a colloidal system composed of
      nanoparticles are probed by a novel experimental setup, which combines homodyne
      and heterodyne dynamic light scattering focused onto a micron-sized volume via a
      microscope objective. The technique is used to measure the four-point
      susceptibility of an aging colloidal suspension, revealing a breakdown of the
      Gaussian approximation for the correlation function of the scattered
      electromagnetic field. The deviation from the Gaussian approximation increases
      with waiting time as the system evolves toward an arrested phase, signaling the
      gradual emergence of higher-order nontrivial dynamic correlations.

PMID- 23002881
TI  - Fano resonances in the midinfrared spectra of single-walled carbon nanotubes.
AB  - This work revisits the physics giving rise to the carbon nanotube phonon bands in
      the midinfrared. Our measurements of doped and undoped samples of single-walled
      carbon nanotubes in Fourier transform infrared spectroscopy show that the phonon
      bands exhibit an asymmetric line shape and that their effective cross section is
      enhanced upon doping. We relate these observations to electron-phonon coupling
      or, more specifically, to a Fano resonance phenomenon. We note that the dopant
      induced intraband (not interband) continuum couples strongly to the phonon modes,
      and that defects created on the sidewall are scattering centers that increase the
      spectral amplitude of the resonance.

PMID- 23002882
TI  - Relaxation dynamics of photoexcited excitons in rubrene single crystals using
      femtosecond absorption spectroscopy.
AB  - The relaxation dynamics of an exciton in rubrene was investigated by femtosecond
      absorption spectroscopy. Exciton relaxation to a self-trapped state occurs via
      the coherent oscillation with 78 cm(-1) due to a coupled mode of molecular
      deformations with phenyl-side-group motions and molecular displacements. From the
      temperature dependence of the decay time of excitons, the energy necessary for an
      exciton to escape from a self-trapped state is evaluated to be ~35 meV (~400 K).
      As a result, a self-trapped exciton is stable at low temperatures. At room
      temperature, excitons can escape from a self-trapped state and, subsequently,
      they are dissociated to charged species. The exciton dissociation mechanism is
      discussed on the basis of the results.

PMID- 23002883
TI  - Optimum photoluminescence excitation and recharging cycle of single nitrogen
      vacancy centers in ultrapure diamond.
AB  - Important features in the spectral and temporal photoluminescence excitation of
      single nitrogen-vacancy (NV) centers in diamond are reported at conditions
      relevant for quantum applications. Bidirectional switching occurs between the
      neutral (NV(0)) and negatively charged (NV(-)) states. Luminescence of NV(-) is
      most efficiently triggered at a wavelength of 575 nm which ensures optimum
      excitation and recharging of NV(0). The dark state of NV(-) is identified as
      NV(0). A narrow resonance is observed in the excitation spectra at 521 nm, which
      mediates efficient conversion to NV(0).

PMID- 23002884
TI  - Superlens in the time domain.
AB  - It has been predicted theoretically and demonstrated experimentally that a planar
      slab supporting surface plasmons or surface phonon polaritons can behave as a
      super lens. However, the resolution is limited by the losses of the slab. In this
      Letter, we point out that the resolution limit imposed by losses can be overcome
      by using time-dependent illumination.

PMID- 23002885
TI  - Spin polarization of photoelectrons from topological insulators.
AB  - We show that the degree of spin polarization of photoelectrons from the surface
      states of topological insulators is 100% if fully polarized light is used as in
      typical photoemission measurements, and, hence, can be significantly higher than
      that of the initial state. Further, the spin orientation of these photoelectrons
      in general can also be very different from that of the initial surface state and
      is controlled by the photon polarization. A rich set of predicted phenomena have
      recently been confirmed by spin- and angle-resolved photoemission experiments.

PMID- 23002886
TI  - Individual atomic-scale magnets interacting with spin-polarized field-emitted
      electrons.
AB  - We resonantly inject spin-polarized field-emitted electrons in thermally
      switching nanomagnets. A detailed lifetime analysis as a function of the spin
      polarized emission current reveals that considerable Joule heating is generated,
      and spin-transfer torque results in a directed switching. A trend of higher
      switching efficiency per electron is observed with an increasing emission
      current, probably due to the excitation of Stoner modes. On a quasistable
      nanomagnet, a spin-polarized emission current in the low nA regime already
      triggers magnetization reversal, thereby demonstrating the high impact of hot
      electron spins onto atomic-scale magnets.

PMID- 23002887
TI  - Structural heterogeneity and diffuse scattering in morphotropic lead zirconate
      titanate single crystals.
AB  - Complementary diffuse and inelastic synchrotron x-ray scattering measurements of
      lead zirconate-titanate single crystals with composition near the morphotropic
      phase boundary (x=0.475) are reported. In the temperature range 293 K<T<400 K a
      highly anisotropic quasielastic diffuse scattering is observed. Above 400 K this
      scattering disappears. Its main features can be reproduced by the model of
      inhomogeneous lattice deformations caused by inclusions of a tetragonal phase
      into a rhombohedral or monoclinic phase. This observation supports the idea that
      PZT at its morphotropic phase boundary is essentially structurally inhomogeneous.

PMID- 23002888
TI  - Continuous theory of active matter systems with metric-free interactions.
AB  - We derive a hydrodynamic description of metric-free active matter: starting from
      self-propelled particles aligning with neighbors defined by "topological" rules,
      not metric zones-a situation advocated recently to be relevant for bird flocks,
      fish schools, and crowds-we use a kinetic approach to obtain well-controlled
      nonlinear field equations. We show that the density-independent collision rate
      per particle characteristic of topological interactions suppresses the linear
      instability of the homogeneous ordered phase and the nonlinear density
      segregation generically present near threshold in metric models, in agreement
      with microscopic simulations.

PMID- 23002889
TI  - Prominent effect of soil network heterogeneity on microbial invasion.
AB  - Using a network representation for real soil samples and mathematical models for
      microbial spread, we show that the structural heterogeneity of the soil habitat
      may have a very significant influence on the size of microbial invasions of the
      soil pore space. In particular, neglecting the soil structural heterogeneity may
      lead to a substantial underestimation of microbial invasion. Such effects are
      explained in terms of a crucial interplay between heterogeneity in microbial
      spread and heterogeneity in the topology of soil networks. The main influence of
      network topology on invasion is linked to the existence of long channels in soil
      networks that may act as bridges for transmission of microorganisms between
      distant parts of soil.

PMID- 23002890
TI  - Stationary vortex loops induced by filament interaction and local pinning in a
      chemical reaction-diffusion system.
AB  - Scroll rings are three-dimensional excitation waves rotating around one
      dimensional filament loops. In experiments with the Belousov-Zhabotinsky reaction
      we show that the collapse of these loops can be stopped by local pinning to only
      two unexcitable heterogeneities. The resulting vortices rotate around stationary
      but curved filaments. The absence of filament motion can be explained by
      repulsive interaction that counteracts the expected curvature-induced motion. The
      shape and key dependencies of the stationary filaments are well described by a
      curvature-flow model with additive interaction velocities that rapidly decrease
      with filament distance.

PMID- 23002891
TI  - Simulations of free-solution electrophoresis of polyelectrolytes with a finite
      Debye length using the Debye-Huckel approximation.
AB  - We introduce a mesoscale simulation method based on multiparticle collision
      dynamics (MPCD) for the electrohydrodynamics of polyelectrolytes with finite
      Debye lengths. By applying the Debye-Huckel approximation to assign an effective
      charge to MPCD particles near charged monomers, our simulations are able to
      reproduce the rapid rise in the electrophoretic mobility with respect to the
      degree of polymerization for the shortest polymer lengths followed by a small
      decrease for longer polymers due to charge condensation. Moreover, these
      simulations demonstrate the importance of a finite Debye length in accurately
      determining the mobility of uniformly charged polyelectrolytes and net neutral
      polyampholytes.

PMID- 23002892
TI  - Concept of a single temperature for highly nonequilibrium laser-induced hydrogen
      desorption from a ruthenium surface.
AB  - Laser-induced condensed phase reactions are often interpreted as nonequilibrium
      phenomena that go beyond conventional thermodynamics. Here, we show by Langevin
      dynamics and for the example of femtosecond-laser desorption of hydrogen from a
      ruthenium surface that light adsorbates thermalize rapidly due to ultrafast
      energy redistribution after laser excitation. Despite the complex reaction
      mechanism involving hot electrons in the surface region, all desorption product
      properties are characterized by equilibrium distributions associated with a
      single, unique temperature. This represents an example of ultrahot chemistry on
      the subpicosecond time scale.

PMID- 23002893
TI  - Rotational diffusion of spherical colloids close to a wall.
AB  - There is currently no experimental technique available to probe spatially
      resolved rotational diffusion of nanoparticles in the vicinity of a wall. We
      present the first experimental study of rotational diffusion of small spherical
      colloids, using dynamic evanescent wave scattering. A setup is used where the
      wave vector components parallel and perpendicular to the wall can be varied
      independently, and an expression is derived for the first cumulant of the
      intensity correlation function in VH evanescent wave geometry for optically
      anisotropic spheres. The experimental results are in agreement with theoretical
      predictions that take particle-wall hydrodynamic interactions into account.

PMID- 23002894
TI  - Stochastic dynamical model of a growing citation network based on a self-exciting
      point process.
AB  - We put under experimental scrutiny the preferential attachment model that is
      commonly accepted as a generating mechanism of the scale-free complex networks.
      To this end we chose a citation network of physics papers and traced the citation
      history of 40,195 papers published in one year. Contrary to common belief, we
      find that the citation dynamics of the individual papers follows the superlinear
      preferential attachment, with the exponent alpha=1.25-1.3. Moreover, we show that
      the citation process cannot be described as a memoryless Markov chain since there
      is a substantial correlation between the present and recent citation rates of a
      paper. Based on our findings we construct a stochastic growth model of the
      citation network, perform numerical simulations based on this model and achieve
      an excellent agreement with the measured citation distributions.

PMID- 23002897
TI  - Self-pollination and parthenocarpic ability in developing ovaries of self
      incompatible Clementine mandarins (Citrus clementina).
AB  - This study aimed to determine if self-pollination is needed to trigger
      facultative parthenocarpy in self-incompatible Clementine mandarins (Citrus
      clementina Hort. ex Tan.). 'Marisol' and 'Clemenules' mandarins were selected,
      and self-pollinated and un-pollinated flowers from both cultivars were used for
      comparison. These mandarins are always seedless after self-pollination and show
      high and low ability to develop substantial parthenocarpic fruits, respectively.
      The time-course for pollen grain germination, tube growth and ovule abortion was
      analyzed as well as that for carbohydrates, active gibberellins (GA1 and GA4 ),
      auxin (IAA) and abscisic acid (ABA) content in the ovary. 'Clemenules' showed
      higher pollen grain germination, but pollen tube development was arrested in the
      upper style 9 days after pollination in both cultivars. Self-pollination did not
      stimulate parthenocarpy, whereas both un-pollinated and self-pollinated ovaries
      set fruit regardless of the cultivar. On the other hand, 'Marisol' un-pollinated
      flowers showed greater parthenocarpic ovary growth than 'Clemenules' un
      pollinated flowers, i.e. higher ovule abortion rate (+21%), higher fruit set
      (+44%) and higher fruit weight (+50%). Further, the greater parthenocarpic
      ability of 'Marisol' paralleled higher levels of GA1 in the ovary (+34% at
      anthesis). 'Marisol' ovary also showed higher hexoses and starch mobilization,
      but lower ABA levels (-64% at anthesis). Self-pollination did not modify
      carbohydrates or GA content in the ovary compared to un-pollination. Results
      indicate that parthenocarpy in the Clementine mandarin is pollination-independent
      with its ability to set depending on the ovary hormone levels. These findings
      suggest that parthenocarpy in fertile self-incompatible mandarins is
      constitutively regulated.

PMID- 23002739
TI  - Search for tb resonances in proton-proton collisions at ?s=7 TeV with the ATLAS
      detector.
AB  - This Letter presents a search for tb resonances in 1.04 fb(-1) of LHC proton
      proton collision data collected by the ATLAS detector at a center-of-mass energy
      of 7 TeV. Events with a lepton, missing transverse momentum, and two jets are
      selected and the invariant mass of the corresponding final state is
      reconstructed. The search exploits the shape of the tb invariant mass
      distribution compared to the expected standard model backgrounds. The model of a
      right-handed W(R)' with standard model-like couplings is chosen as the benchmark
      model for this search. No statistically significant excess of events is observed
      in the data, and upper limits on the cross section times the branching ratio of
      W(R)' resonances at 95% C.L. lie in the range of 6.1-1.0 pb for W(R)' masses
      ranging from 0.5 to 2.0 TeV. These limits are translated into a lower bound on
      the allowed right-handed W(R)' mass, giving m(W(R)'))>1.13 TeV at 95% C.L.

PMID- 23002898
TI  - Prevalence of protein-energy wasting and its various types in Iranian
      hemodialysis patients: a new classification.
AB  - BACKGROUND: This study was designed to determine the prevalence of protein-energy
      wasting (PEW) and its various types in hemodialysis (HD) patients in Tehran,
      Iran. METHODS: For this cross-sectional study, 291 HD patients were randomly
      selected. The nutritional status of the patients was determined by subjective
      global assessment (SGA) and their dietary intakes were assessed using a 4-day
      dietary recall. In addition, serum high-sensitive C-reactive protein (hs-CRP) was
      measured. RESULTS: The prevalence of mild-to-moderate and severe PEW based on SGA
      was 60.5% and 1% in Tehran HD patients, respectively. The prevalence of various
      types of PEW in HD patients was 20.5% type I (inadequate energy or protein intake
      without inflammation), 65.5% type IIa (inadequate energy or protein intake with
      inflammation), and 14% type IIb (adequate energy and protein intake with
      inflammation). Of the total HD patients with no PEW based on SGA, about 3.5% had
      type 0 normal nutritional status (adequate energy and protein intake without
      inflammation), 34% had type I normal nutritional status (inadequate energy or
      protein intake without inflammation), 55.5% had type IIa normal nutritional
      status (inadequate energy or protein intake with inflammation), and 7% had type
      IIb normal nutritional status (adequate energy and protein intake with
      inflammation). CONCLUSION: PEW in Tehran HD patients is considerably prevalent
      and PEW type IIa is the most common type. In addition, HD patients with no PEW
      based on SGA should also be paid attention because they may be in the early
      stages of inadequate intake of energy and/or protein and inflammation.

PMID- 23002899
TI  - Social inclusion and people with intellectual disability and challenging
      behaviour: a systematic review.
AB  - BACKGROUND: Social inclusion is central to disability policies internationally.
      The high risk of social exclusion for people with intellectual disability is
      compounded for those with challenging behaviour. METHOD: A systematic literature
      review examined how social inclusion of people with intellectual disability and
      challenging behaviour has been researched and operationalised in the empirical
      literature, and aimed to determine what evidence exists about the extent of
      social inclusion by people with intellectual disability and challenging
      behaviour. RESULTS: A thematic analysis of the 14 papers identified that social
      inclusion has been poorly defined and measured, and that the little research that
      has occurred in respect of people with challenging behaviour has demonstrated
      their potential to be socially included. CONCLUSIONS: Clearer conceptualisation
      of inclusion, and greater understanding of practices that support social
      inclusion and system level mechanisms, which ensure goals around inclusion gain
      prominence in funding and support plans, may address the neglect of this critical
      quality-of-life domain for people with challenging behaviour.

PMID- 23002903
TI  - Recurrent pseudotumor of the urinary bladder managed by revision hip
      arthroplasty.

PMID- 23002900
TI  - Superhydrophilic thin-film composite forward osmosis membranes for organic
      fouling control: fouling behavior and antifouling mechanisms.
AB  - This study investigates the fouling behavior and fouling resistance of
      superhydrophilic thin-film composite forward osmosis membranes functionalized
      with surface-tailored nanoparticles. Fouling experiments in both forward osmosis
      and reverse osmosis modes are performed with three model organic foulants:
      alginate, bovine serum albumin, and Suwannee river natural organic matter. A
      solution comprising monovalent and divalent salts is employed to simulate the
      solution chemistry of typical wastewater effluents. Reduced fouling is
      consistently observed for the superhydrophilic membranes compared to control thin
      film composite polyamide membranes, in both reverse and forward osmosis modes.
      The fouling resistance and cleaning efficiency of the functionalized membranes is
      particularly outstanding in forward osmosis mode where the driving force for
      water flux is an osmotic pressure difference. To understand the mechanism of
      fouling, the intermolecular interactions between the foulants and the membrane
      surface are analyzed by direct force measurement using atomic force microscopy.
      Lower adhesion forces are observed for the superhydrophilic membranes compared to
      the control thin-film composite polyamide membranes. The magnitude and
      distribution of adhesion forces for the different membrane surfaces suggest that
      the antifouling properties of the superhydrophilic membranes originate from the
      barrier provided by the tightly bound hydration layer at their surface, as well
      as from the neutralization of the native carboxyl groups of thin-film composite
      polyamide membranes.

PMID- 23002901
TI  - Decline in physical function and risk of elder abuse reported to social services
      in a community-dwelling population of older adults.
AB  - OBJECTIVES: To examine the longitudinal association between decline in physical
      function and risk of elder abuse. DESIGN: Prospective population-based study.
      SETTING: Geographically defined community in Chicago. PARTICIPANTS: One hundred
      forty-three Chicago Health and Aging Project (CHAP) participants who had elder
      abuse reported to a social services agency from 1993 to 2010 were identified.
      PARTICIPANTS: The primary independent variable was objectively assessed physical
      function using decline in physical performance testing (tandem stand, measured
      walk, and chair stand). Secondary independent variables were assessed using
      decline in self-reported Katz, Nagi, and Rosow-Breslau scale scores. Dependent
      variables were reported and confirmed elder abuse and specific subtypes of elder
      abuse (physical, psychological, caregiver neglect, and financial exploitation).
      Logistic regression models were used to assess the association between decline in
      physical function measures and risk of elder abuse. RESULTS: After adjusting for
      potential confounders, decline in physical performance testing (odds ratio (OR) =
      1.13, 95% confidence interval (CI) = 1.06-1.19), Katz impairment (OR = 1.29, 95%
      CI = 1.15-1.45), Nagi impairment (OR = 1.30, 95% CI = 1.13-1.49), and Rosow
      Breslau impairment (OR = 1.42, 95% CI = 1.15-1.74) was associated with greater
      risk for elder abuse. The lowest tertile of physical performance testing (OR =
      4.92, 95% CI = 1.39-17.46) and the highest tertiles of Katz impairment (OR =
      3.99, 95% CI = 2.18-7.31), Nagi impairment (2.37, 95% CI = 1.08-5.23), and Rosow
      Breslau impairment (OR = 2.85, 95% CI = 1.39-5.84) were associated with greater
      risk of elder abuse. CONCLUSION: Decline in objectively assessed physical
      function and self-reported physical function are associated with greater risk for
      elder abuse.

PMID- 23002902
TI  - Bioassay-guided investigation of the Tanzanian plant Pyrenacantha kaurabassana
      for potential anti-HIV-active compounds.
AB  - Two new anti-HIV xanthones, 6,7,11-trihydroxy-10-methoxy-9-(7-methoxy-3-methyl-1
      oxoisochroman-5-yl)-2-methyl-12-oxo-12H-benzo[b]xanthene-4-carboxylic acid (1)
      and 6,7-dihydroxy-10,11-dimethoxy-9-(7-methoxy-3-methyl-1-oxoisochroman-5-yl)-2
      methyl-12-oxo-12H-benzo[b]xanthene-4-carboxylic acid (2), and a new
      hexadecahydrochrysen-3-ol (3) were isolated from the tubers of Pyrenacantha
      kaurabassana. Compounds 1 and 2 showed moderate anti-HIV activity when tested in
      the deCIPhR assay on HIV virus type NL4-3, with IC50 values of 21 and 2 MUg/mL,
      respectively.

PMID- 23002904
TI  - Heterodimers reveal that two arabinose molecules are required for the normal
      arabinose response of AraC.
AB  - AraC protein, which regulates expression of the l-arabinose operon in Escherichia
      coli, is a dimer whose DNA binding affinity for pairs of DNA half-sites is
      controlled by arabinose. Here we have addressed the question of whether the
      arabinose response of AraC requires the binding of one or two molecules of
      arabinose. This was accomplished by measuring the DNA dissociation rates of wild
      type AraC and heterodimeric AraC constructs in which one subunit is capable of
      binding arabinose and the other subunit does not bind arabinose. Solutions
      consisting entirely of heterodimers were formed by spontaneous subunit exchange
      between two different homodimers, with heterodimers being trapped by the
      formation of an intersubunit disulfide bond between cysteine residues
      strategically positioned within the dimerization interface. We found that the
      normal arabinose response of AraC requires the binding of two arabinose
      molecules. These results provide additional constraints on mechanistic models for
      the action of AraC.

PMID- 23002905
TI  - Synthesis of polyfunctionalized quinolines via the sequence of propargyl-allenyl
      isomerization and aza-electrocyclization.
AB  - Quinoline derivatives are important heterocyclic compounds because of their
      natural occurrence and applications in pharmaceutical fields. In this paper, a
      sequence of propargyl-allenyl isomerization and aza-electrocyclization for the
      synthesis of polyfunctionalized quinolines are described.

PMID- 23002906
TI  - Bayesian hypothesis testing in two-arm trials with dichotomous outcomes.
AB  - This article is motivated by an interest in comparing inferences made when using
      a Bayesian or frequentist statistical approach. The article addresses the study
      of one-sided superiority and noninferiority Bayesian tests. These tests are
      stated in terms of the posterior probability that the null hypothesis is true for
      the binomial distribution and in terms of one-sided credible limits. We restrict
      our considerations to conjugate beta priors with integer parameters. Under this
      assumption, the posterior probabilities of tested hypotheses can be transformed
      into the frequentist probabilities of Bernoulli trials with an adjusted number of
      events and population sizes. The method resembles a standard frequentist problem
      formulation. By using an appropriate choice of prior parameters, the posterior
      probabilities of the null hypothesis can be made smaller or larger than the p
      values of frequentist tests.

PMID- 23002907
TI  - Practical implications of choice of test in National Institute for Health and
      Clinical Excellence (NICE) guidance for the prevention of Type 2 diabetes.

PMID- 23002908
TI  - Evaluation of fibrosis in precision-cut tissue slices.
AB  - 1.In this review, the use of precision-cut tissue slices (PCTS) of the liver,
      kidney, lung and intestine in fibrosis research are evaluated and future
      possibilities are discussed. 2.In vivo models or techniques that are applicabless
      to be investigated in PCTS are discussed. 3.It is concluded that the early onset
      of fibrosis can be induced successfully in PCTS prepared from human and
      experimental animals. 4.Moreover, precision-cut slices of fibrotic tissue are
      effective in gaining new knowledge of the mechanisms of fibrosis and of the mode
      of action of potential antifibrotic drugs. 5.Both healthy and fibrotic human
      tissue slices will pave the way for the testing of novel therapeutic drugs to
      treat patients with fibrosis avoiding interspecies extrapolation.

PMID- 23002909
TI  - Evaluation of a mitochondrial disease criteria scoring system on mitochondrial
      encephalomyopathy in Chinese patients.
AB  - Due to the complicated clinical features of mitochondrial encephalomyopathy,
      simplified mitochondrial disease criteria (MDC) have recently been established in
      Europe. This study evaluated the sensitivity and specificity of this scoring
      system in Chinese patients. Seventy-eight patients with suspected mitochondrial
      encephalomyopathy were recruited to be scored by the simplified MDC and were
      further classified into "possible" (2-4), "probable" (5-7), or "definite"
      categories (>=8). Significant differences were observed between the total scores
      in the mitochondrial encephalomyopathy group and the other myopathy group. In the
      mitochondrial encephalomyopathy group, 73.5% of patients had a score above 8,
      whereas in the other myopathy group, the "definite" percentage was only 3.2%,
      suggesting the proposed MDC scoring system has a high sensitivity for diagnosis
      of mitochondrial encephalomyopathy in China. Moreover, there were significant
      differences in the clinical scores and imaging portions of the MDC, suggesting
      that the simplified MDC may distinguish mitochondrial disorder from other
      multisystem disorders to aid in early diagnosis prior to a muscle biopsy.

PMID- 23002911
TI  - Resistant invasive aspergillosis in an autosomal recessive chronic granulomatous
      disease.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency
      characterized by severe bacterial and fungal infections. Invasive aspergillosis
      and other rare mold diseases are the leading causes of mortality. We report one
      case of CGD revealed by retropharyngeal abscess. On evolution, the patient
      developed an invasive aspergillosis resistant to treatment.

PMID- 23002910
TI  - Identification of effective strategies to promote language in deaf children with
      cochlear implants.
AB  - Parental involvement and communication are essential for language development in
      young children. However, hearing parents of deaf children face challenges in
      providing language input to their children. This study utilized the largest
      national sample of deaf children receiving cochlear implants, with the aim of
      identifying effective facilitative language techniques. Ninety-three deaf
      children (<= 2 years) were assessed at 6 implant centers prior to and for 3 years
      following implantation. All parent-child interactions were videotaped,
      transcribed, and coded at each assessment. Analyses using bivariate latent
      difference score modeling indicated that higher versus lower level strategies
      predicted growth in expressive language and word types predicted growth in
      receptive language over time. These effective, higher level strategies could be
      used in early intervention programs.

PMID- 23002912
TI  - Alcohol intake induces diminished ovarian reserve in childbearing age women.
AB  - AIM: To investigate the adverse effects of alcohol on ovarian reserve in women of
      childbearing age. MATERIAL AND METHODS: Twenty bar hostesses between the ages of
      18 and 29 with moderate alcohol consumption for over 3 years and 16 healthy women
      between the ages of 18 and 28 with alcohol consumption under a healthy standard
      were recruited. Their ovarian reserve was evaluated by measuring menstrual cycle
      day three (CD3) serum follicle stimulating hormone (FSH), luteinizing hormone
      (LH), estradiol (E2), prolactin (PRL) and testosterone (TST) levels, and by
      transvaginal B-ultrasound examination of uterine size, ovarian size and number of
      antral follicles. RESULTS: Moderate consumption of alcohol significantly
      increased serum FSH level (P=0.001), but had no effect on serum LH, E2, PRL and
      TST levels. Moderate alcohol consumption significantly decreased ovarian volume
      (P=0.000) and number of ovarian antral follicles (P=0.015), but had no effect on
      uterus size. Moderate alcohol consumption significantly increased the occurrence
      of menstrual flow abnormalities (P=0.001 and P=0.036, respectively), but had no
      effect on menstrual cycle. The amount of alcohol consumed positively correlated
      with FSH, and negatively correlated with ovarian volume and number of antral
      follicles in women with moderate alcohol consumption. CONCLUSION: Long-term
      moderate alcohol consumption may lead to diminished ovarian reserve.

PMID- 23002913
TI  - Field evaluations of disposable sticky lures for surveillance of Aedes aegypti
      (Stegomyia aegypti) and Culex quinquefasciatus in Jakarta.
AB  - From December 1997 to April 1998, disposable sticky lures (1608 lure days) were
      trialled in homes in north Jakarta, Indonesia as surveillance tools for Aedes
      aegypti (Stegomyia aegypti) (Diptera: Culicidae) and Culex quinquefasciatus
      (Diptera: Culicidae), referenced to indoor resting adult collections (92 * 10
      min). The lures collected 89.4% of the total of 1339 Ae. aegypti and 92.1% of the
      total of 1272 Cx. quinquefasciatus collected by all methods. Because there were
      no significant differences with respect to numbers collected in bedrooms, living
      rooms and kitchens, bedrooms were selected for subsequent trials for reasons of
      convenience. The main trials involved a replicated complete block design with L
      lysine and sodium carbonate. Lures without attractant or with four different
      dilutions of L-lysine collected 3.4-8.5 times more Ae. aegypti and 4.2-8.1 times
      more Cx. quinquefasciatus than were collected by mouth aspirator. Lures with or
      without dilutions of sodium carbonate collected 2.7-5.0 times more Ae. aegypti
      and 1.8-4.2 times more Cx. quinquefasciatus than aspirator collections. The
      precision associated with catches of sticky lures was better than that for
      aspirator collections. Although olfactants generally improved the numbers of
      mosquitoes collected, the differences in catch between lures with and without
      attractants were usually non-significant. Any deficit in catch may be offset by
      increasing the surveillance period to >=30 days to detect all four dengue
      serotypes from infected mosquitoes. 

PMID- 23002914
TI  - The prevalence of platybasia in patients with velopharyngeal incompetence.
AB  - Objectives : To estimate the prevalence of platybasia in patients with
      velopharyngeal incompetence (VPI) and its relation with palatal anomalies and
      syndromes. Design and Settings : Retrospective case analysis. Setting : A
      university-affiliated hospital. Patients : The VPI patients (n = 366) included
      five groups with either cleft lip and palate (CLP), cleft palate (CP) only,
      submucous cleft palate (SMCP), occult submucous cleft palate (OSMCP), or non-CP.
      The control group (n = 126) comprised healthy, normal-speech individuals. Outcome
      Measures : The cranial-base angle was measured by lateral cephalometric
      radiography. The prevalence of platybasia (defined as cranial base angle >= 137
      degrees ) was estimated and the patient's syndromes were recorded. Results : The
      prevalence of platybasia was significantly higher in the VPI group (28.7%) than
      in the normal controls (2.4%) (P < .001). A significant difference (P < .01) was
      found in the prevalence of platybasia among the five VPI groups: 16.7%, 20.3%,
      28.8%, 33.7%, and 40.3% for CLP, CP only, SMCP, OSMCP, and non-CP, respectively.
      No significant difference was found between the cranial-base angle of VPI
      patients and of controls and between the cranial-base angle of the five VPI
      groups. The VPI nonplatybasic patients had a significantly smaller cranial-base
      angle than normal controls (P < .01). Platybasia was the highest among patients
      with velocardiofacial syndrome (50%), followed by those with Pierre Robin
      syndrome (27.3%). Conclusions : Platybasia, which may cause enlargement of the
      nasopharyngeal space and difficulties in achieving velopharyngeal closure, can be
      found in high numbers of VPI patients with or without CP. This supports the
      belief that velopharyngeal anomaly may be part of a more complex craniofacial
      anomaly influenced by the cranial-base flexure. 

PMID- 23002915
TI  - Molecular mechanism of surface-assisted epitaxial self-assembly of amyloid-like
      peptides.
AB  - A surprising "upright" fibrilar conformation (with a height of ~2.6 nm) was
      observed with in situ atomic force microscopy (AFM) for an amyloid-like peptide
      (NH(2)-VGGAVVAV-COHN(2)) on mica surface, which is very different from its "flat"
      conformation (with a much smaller height of ~0.9 nm) on the HOPG surface. Our all
      atom molecular dynamics (MD) simulations reveal that it is the strong
      electrostatic interactions between the N-terminus of the peptide and the mica
      surface that result in an upright conformation and a highly ordered beta-stranded
      structure on mica, with a height of 2.5 +/- 0.1 nm, consistent with the AFM
      experiment. Similarly, our MD simulations show that the same peptides adopt a
      flat conformation on HOPG surfaces due to the favorable hydrophobic interactions
      with HOPG. Our simulations also indicate that epitaxial patterns found in mica
      are preferentially controlled by anisotropic binding sites commensurate with the
      inherent crystallographic unit cell of the basal substrate.

PMID- 23002916
TI  - Dipper and non-dipper blood pressure 24-hour patterns: circadian rhythm-dependent
      physiologic and pathophysiologic mechanisms.
AB  - Neuroendocrine mechanisms are major determinants of the normal 24-h blood
      pressure (BP) pattern. At the central level, integration of the major driving
      factors of this temporal variability is mediated by circadian rhythms of
      monoaminergic systems in conjunction with those of the hypothalamic-pituitary
      adrenal, hypothalamic-pituitary-thyroid, opioid, renin-angiotensin-aldosterone,
      plus endothelial systems and specific vasoactive peptides. Humoral secretions are
      typically episodic, coupled either to sleep and/or the circadian endogenous
      (suprachiasmatic nucleus) central pacemaker clock, but exhibiting also weekly,
      monthly, seasonal, and annual periodicities. Sleep induction and arousal are
      influenced also by many hormones and chemical substances that exhibit 24-h
      variation, e.g., arginine vasopressin, vasoactive intestinal peptide, melatonin,
      somatotropin, insulin, steroids, serotonin, corticotropin-releasing factor,
      adrenocorticotropic hormone, thyrotropin-releasing hormone, endogenous opioids,
      and prostaglandin E2, all with established effects on the cardiovascular system.
      As a consequence, physical, mental, and pathologic stimuli that activate or
      inhibit neuroendocrine effectors of biological rhythmicity may also interfere
      with, or modify, the temporal BP structure. Moreover, immediate adjustment to
      exogenous components/environment demands by BP rhythms is modulated by the
      circadian-time-dependent responsiveness of biological oscillators and their
      neuroendocrine effectors. This knowledge contributes to a better understanding of
      the pathophysiology of abnormalities of the 24-h BP pattern and level and their
      correction through circadian rhythm-based chronotherapeutic strategies.

PMID- 23002917
TI  - Determination of the concentration of potential efflux pump inhibitors,
      pheophorbide a and pyropheophorbide a, in the feces of animals by fluorescence
      spectroscopy.
AB  - Efflux pumps are vital bacterial components, and research has demonstrated that
      some plant compounds such as pheophorbide a (php) possess efflux pump inhibitor
      (EPI) activity. This study determined the quantity of php present in feces as an
      indicator of EPI activity. Feces were collected from different species of animals
      fed a variety of feeds. The chlorophyll metabolites php and pyropheophorbide a
      (pyp) were determined using fluorescense spectroscopy. The average concentrations
      [MUg/g dry matter (DM) feces] of pyp/php in feces were as follows: guinea pig,
      180; goat, 150; rabbit, 150; dairy cow, 120; feedlot cattle, 60; rat, <1; pig,
      <1; chicken, <1. These data indicate that animals consuming "green" diets will
      excrete feces with concentrations of php/pyp that exceed levels demonstrated to
      be inhibitory to bacterial efflux pumps (0.5 MUg/mL). The natural presence EPIs
      in the gastrointestinal tract may modulate the activity of microbial efflux pumps
      and exert selection pressure upon resident microbial populations.

PMID- 23002918
TI  - Hormone therapy use and breast cancer incidence by histological subtypes in
      Sweden and Norway.
AB  - Mammography screening and postmenopausal hormone therapy (HT) both influence
      breast cancer incidence. While breast cancer incidence increased by around 50%
      during the introduction of screening, a smaller decline in incidence has been
      reported in several countries after 2002 when the sales of HT started to decline.
      Data suggest that HT increases the risk of the second most common type of breast
      cancer, invasive lobular carcinoma (ILC) but not the most common, invasive ductal
      carcinoma (IDC). Breast cancer incidences stratified on histological subtypes
      were obtained from the national cancer registries. HT sales data from drug
      consumption statistics and information on the county-level introduction of
      mammography screening were combined, and breast cancer incidence trends were
      estimated using Poisson regression models, focusing on the period after 2002.
      From 2002 to 2007 the annual decrease in breast cancer incidence rates for women
      aged 50-69 was 1.5% (95% CI -2.3% to -0.7%) in Sweden and 0.8% (95% CI -2.8% to
      1.2%) in the part of Norway not confounded by prevalence screening. Most of the
      decline was in the rates of ILC which dropped by 4.7% (95% CI -6.6% to -2.7%) and
      7.0% (95% CI -12.8% to -0.9%) per year, respectively. The rates of IDC were
      stable in this period. Breast cancer incidence has declined in Sweden and Norway
      since 2002, but the reduction is moderate compared with the large increase that
      occurred during the introduction of mammography screening. Declining rates of
      ILC, but not of IDC, support the hypothesis that the drop in breast cancer
      incidence is associated with reduced HT use.

PMID- 23002919
TI  - Smoking initiation and personal characteristics of secondary students in Hong
      Kong.
AB  - AIM: To explore the relationship between personal characteristics and smoking
      initiation among adolescents in Hong Kong. BACKGROUND: Adolescents have been
      initiating cigarette smoking at an increasing rate in recent years. Preventing
      tobacco use among young children has become one of the most effective strategies
      to reduce the harmful effects of tobacco use. DESIGN: A cross-sectional study.
      METHODS: Secondary students were recruited by convenience sampling from schools
      in the New Territories of Hong Kong in 2010. Questionnaires were used to collect
      information relating to their demographic and personal characteristics, including
      behavioural control, coping styles, sociability, locus of control,
      rebelliousness, self-esteem, emotional distress, and intention to smoke. RESULTS:
      A total of 644 secondary students were recruited. The prevalence of having ever
      tried smoking was 19.4% and that of regular smoking was 3.9% among these
      students. The results of this study show that secondary students who were living
      in public housing and had lower behavioural control and higher smoking intention
      were more likely to have tried smoking or to be regular smokers, indicating that
      these factors contribute to smoking initiation among secondary students.
      CONCLUSIONS: The personal characteristics of secondary students do play a role in
      smoking initiation. Parents and school personnel should work together to help
      young people to improve their self-esteem and behavioural control and to overcome
      their rebelliousness. The causes of smoking intention should also be explored to
      stop young people from picking up their first cigarette.

PMID- 23002920
TI  - Surface coatings shape the protein corona of SPIONs with relevance to their
      application in vivo.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) have proved their use in many
      biomedical applications, such as drug delivery, hyperthermia, and MRI (magnetic
      resonance imaging) contrast agents. Due to their instability in fluids, several
      surface coatings have been used to both stabilize and tune the properties of
      these nanoparticles (NPs) according to their applications. These coatings will
      strongly modify their surface properties and influence their interaction with the
      environment proteins in a relevant biological medium with a clear impact on their
      function. It is well-accepted that a protein corona is immediately formed when
      nanoparticles come in contact with a biological milieu, and the emergent bionano
      interface represents the biological identity of the particles. Here, we
      investigate how a different coating on the same magnetic core can influence the
      protein corona composition and structure with clear relevance to application of
      these NPs in medicine. In particular, we have studied the structure and
      composition of the protein corona-SPION complexes of magnetite nanoparticles
      stabilized with citric acid, poly(acrylic acid), or double layer oleic acid by a
      range of approaches, including dynamic light scattering, nanoparticle tracking
      analysis, differential centrifugal sedimentation, infrared spectroscopy, 1-D SDS
      gel electrophoresis, and mass spectroscopy.

PMID- 23002921
TI  - Older adults have greater difficulty imagining future rather than atemporal
      experiences.
AB  - Episodic future thinking refers to mentally traveling forward in time to
      preexperience an event, and emerging research suggests that this is more
      difficult for older adults. The current study was designed to better understand
      the effect of aging on separate component processes of age differences in
      episodic future thinking. Young (n = 24) and older (n = 25) adults were asked to
      construct a) atemporal scenarios, b) future scenarios, and c) a narrative that
      involved navigation. Each of these conditions assesses the capacity to construct
      and describe a scene, but only the future scenario requires a subjective sense of
      self in time (autonoetic consciousness). The composite measure of performance
      showed that relative to young adults, older adults have substantially reduced
      capacity for all three types of construction, suggesting that age-related
      difficulty imagining future episodic events may reflect a more general cognitive
      decline with age. In addition, older adults were worse at imagining future
      experiences than atemporal experiences, indicating limited capacity for
      autonoetic consciousness. Further, this difference between imagining atemporal
      and future experiences was not as evident among younger adults. These deficits in
      episodic future thinking have implications for the daily lives of older adults in
      terms of anticipating and planning for the future.

PMID- 23002922
TI  - Challenges of developing communicative interaction in individuals with congenital
      profound intellectual and multiple disabilities.
AB  - BACKGROUND: Physiological responses have been used in individuals with acquired
      disability to enable communicative interaction without motor movement. This study
      explored four autonomic nervous system (ANS) signals-electrodermal activity, skin
      temperature, cardiac patterns and respiratory patterns-to enable interaction with
      individuals born with profound intellectual and multiple disabilities (PIMD).
      METHOD: A series of case studies were conducted to teach a 15-year-old individual
      with PIMD to voluntarily control his ANS signals for the purposes of
      communicative interaction. Training was carried out according to an alternating
      treatment single-subject research design. RESULTS: Training was unsuccessful;
      however, ANS signal patterns revealed issues unique to people with PIMD: profound
      intrasubject variability, discrepancy between physiological responses and
      caregiver perspectives, and the participant's lack of contingency awareness.
      CONCLUSIONS: These three priority areas unique to people with congenital PIMD
      must be addressed before ANS signals can be used to enable communicative
      interaction with this population.

PMID- 23002924
TI  - Cytotoxic iridoids from the roots of Patrinia scabra.
AB  - Six new iridoid glucosides, patriridosides D-I (1-6), and one new iridoid,
      scabrol A (7), along with 12 known non-glycosidic and glycosidic iridoids (8-19),
      have been isolated from an ethanolic extract of the roots of Patrinia scabra. The
      cytotoxic activity of the isolated compounds against human cervical carcinoma
      HeLa cells and gastric carcinoma MNK-45 cells was evaluated using the MTT assay.
      Compounds 1, 4-6, 8, and 18 showed cytotoxic activities against the MNK-45 cell
      line with respective IC50 values of 15.6, 8.7, 9.4, 30.9, 23.8, and 11.2 MUM,
      while only compound 10 showed cytotoxicity against the HeLa cell line, with an
      IC50 value of 24.5 MUM.

PMID- 23002925
TI  - Antifibrotic effects of pirfenidone in rat proximal tubular epithelial cells.
AB  - OBJECTIVE: Renal fibrosis is a common cause of renal dysfunction with chronic
      kidney disease. We previously investigated the renoprotective effects of the
      antifibrotic agent pirfenidone in a rat model of subtotal nephrectomy. Here, we
      further evaluated the antifibrotic effects of pirfenidone in rat proximal tubular
      epithelial cells. METHODS: NRK52E cells were incubated in a medium containing
      either transforming growth factor (TGF)-beta1 (3 ng/mL) or platelet-derived
      growth factor (PDGF)-BB (5 Ang/mL) or both, with or without pirfenidone (0.1-1
      mmol/L), for 24 h to assess mRNA expression, for 48 h to assess protein
      production, and for 1 h or various time (5-120 min) to assess phosphorylation of
      signal kinase. RESULTS: TGF-beta1, a key mediator in renal fibrosis, induced
      increases in the mRNA expression of various profibrotic factors and extracellular
      matrix, including plasminogen activator inhibitor type 1 (PAI-1), fibronectin,
      type 1 collagen, and connective tissue growth factor (CTGF)-increases which
      pirfenidone significantly inhibited. Specifically, pirfenidone potently inhibited
      TGF-beta1-induced increases in the mRNA expression and protein secretion of PAI
      1, an effect mediated, at least in part, via the mitogen-activated protein kinase
      kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Further, PDGF
      BB, which has been implicated in renal interstitial fibrosis, potently activated
      PAI-1 expression under TGF-beta1 stimulation, and pirfenidone significantly
      inhibited TGF-beta1- and PDGF-BB-induced increases in PAI-1 expression.
      CONCLUSIONS: Taken together, these results suggest that TGF-beta1 closely
      correlates with renal fibrosis in cooperation with several fibrosis-promoting
      molecules, such as PAI-1 and PDGF, in rat proximal tubular epithelial cells, and
      pirfenidone inhibits TGF-beta1-induced fibrosis cascade and will therefore likely
      exert antifibrotic effects under pathological conditions.

PMID- 23002926
TI  - Elevated 1-h plasma glucose following 75-g oral glucose load is a predictor of
      arterial stiffness in subjects with normal glucose tolerance.
AB  - AIMS: The study aimed to investigate arterial stiffness in subjects with normal
      glucose tolerance. METHODS: BMI, systolic blood pressure, fasting plasma glucose,
      lipid variables, ankle-brachial pressure index and brachial-ankle pulse wave
      velocity were measured in 2059 subjects from Takasaki city, located approximately
      100 km north of Tokyo in Japan. Following a 75-g oral glucose tolerance test,
      only subjects with normal glucose tolerance were selected. RESULTS: One-hour post
      challenge plasma glucose levels were correlated with brachial-ankle pulse wave
      velocity values (r = 0.340, P < 0.0001). When subjects with normal glucose
      tolerance were divided into three groups-group 1 (1-h plasma glucose < 8.56
      mmol/l, n = 1595), group 2 (1-h plasma glucose >= 8.56 and < 10.17 mmol/l, n =
      334) and group 3 (1-h plasma glucose >= 10.17 mmol/l, n = 130)-the brachial-ankle
      pulse wave velocity of group 3 (1473 +/- 322 cm/s) was significantly higher than
      that of group 2 (1355 +/- 252 cm/s) and brachial-ankle pulse wave velocity of
      group 2 was also significantly higher than that of group 1 (1275 +/- 212 cm/s).
      CONCLUSIONS: We have identified that, in normal glucose tolerance, arterial
      stiffness is advanced in subjects with higher 1-h post-challenge plasma glucose
      in spite of the normal range for BMI, systolic blood pressure, fasting plasma
      glucose and lipid variables. Higher 1-h plasma glucose level is a risk factor for
      arterial stiffness in normal glucose tolerance.

PMID- 23002927
TI  - Effects of lanthanoid cations on the first electronic transition of liquid water
      studied using attenuated total reflection far-ultraviolet spectroscopy: ligand
      field splitting of lanthanoid hydrates in aqueous solutions.
AB  - The effects of the lanthanoid cations (Ln(3+)) on the first electronic transition
      (A <- X) of liquid water were studied from the attenuated total reflection far
      ultraviolet (ATR-FUV) spectra of trivalent Ln(3+) electrolyte solutions (1 M),
      except Pm(3+). The A <- X transition energies of the Ln(3+) electrolyte solutions
      show a distinct tetrad in their dependence on the number of 4f electrons of the
      Ln(3+) cations. For the half occupation period of the 4f electrons, the A <- X
      transition energies decrease from La(3+) (4f(0), 8.0375 eV) to Nd(3+) (4f(3),
      8.0277 eV) and increase from Sm(3+) (4f(5), 8.0279 eV) to Gd(3+) (4f(7), 8.0374
      eV). For the complete occupation period, there are two local minima at Dy(3+)
      (4f(9), 8.0349 eV) and Yb(3+) (4f(13), 8.0355 eV). The A <- X transition energies
      of the tetrad nodes (La(3+), Gd(3+), Ho(3+) (4f(10)), and Lu(3+) (4f(14)))
      increase slightly, as the nuclear charge increases in accordance with the
      hydration energies of the Ln(3+) cations. The energy difference (DeltaE) between
      the A <- X transition energies and the line between La(3+) and Lu(3+) is largest
      at Nd(3+) (80.5 cm(-1)) for the half occupation period and at Dy(3+) (26.1 cm(
      1)) and Yb(3+) (24.5 cm(-1)) for the complete occupation period. The order of
      magnitude of DeltaE is comparable to the ligand field splitting (LFS) of the
      ground state multiplets of Ln(3+) complexes. The observed tetrad trend of the A <
      X transition energies of the Ln(3+) electrolyte solutions across the 4f period
      reflects the hydration energies of the Ln(3+) cations and the LFS induced by
      water ligands.

PMID- 23002928
TI  - The role of failure modes and effects analysis in showing the benefits of
      automation in the blood bank.
AB  - BACKGROUND: Failure modes and effects analysis (FMEA) is a risk management tool
      used by the manufacturing industry but now being applied in laboratories. STUDY
      DESIGN AND METHODS: Teams from six South Korean blood banks used this tool to map
      their manual and automated blood grouping processes and determine the risk
      priority numbers (RPNs) as a total measure of error risk. RESULTS: The RPNs
      determined by each of the teams consistently showed that the use of automation
      dramatically reduced the RPN compared to manual processes. In addition, FMEA
      showed where the major risks occur in each of the manual processes and where
      attention should be prioritized to improve the process. Despite no previous
      experience with FMEA, the teams found the technique relatively easy to use and
      the subjectivity associated with assigning risk numbers did not affect the
      validity of the data. CONCLUSION: FMEA should become a routine technique for
      improving processes in laboratories.

PMID- 23002930
TI  - A selective, sensitive, colorimetric, and fluorescence probe for relay
      recognition of fluoride and Cu(II) ions with "off-on-off" switching in ethanol
      water solution.
AB  - Anion to cation relay recognition was designed and realized for the first time
      with sequence specificity (F(-)->Cu(2+)) via a fluorescence "off-on-off"
      mechanism. Probe 1 was a highly selective, sensitive, and turn-on chemodosimeter
      for F(-) through a specific cyclization reaction triggered by the strong affinity
      of fluoride toward silicon with a significant change of fluorescence color in
      both ethanol and ethanol-water (1:1, v/v) solution. Fluorescence enhancement
      factors were dramatic: 833-fold in ethanol and 164-fold in ethanol-water (1:1,
      v/v) solution, respectively. The in situ system generated from the sensing of F(
      ) showed good relay recognition ability for Cu(2+) via fast fluorescence
      quenching by the formation of a 1:1 complex in ethanol-water (1:1, v/v) solution.
      The isolated pure compound 2 also exhibited high selectivity toward Cu(2+) in PBS
      buffer (pH = 7.0) solution. The origin of this sequence specificity of
      fluorescence recognition was disclosed through the crystal or optimized
      structures and DFT calculations of corresponding compounds.

PMID- 23002931
TI  - Improving brain signaling in aging: Could berries be the answer?

PMID- 23002929
TI  - Reining in polyoma virus associated nephropathy: design and characterization of a
      template mimicking BK viral coat protein cellular binding.
AB  - The BK polyoma virus is a leading cause of chronic post kidney transplantation
      rejection. One target for therapeutic intervention is the initial association of
      the BK virus with the host cell. We hypothesize that the rate of BKV infection
      can be curbed by competitively preventing viral binding to cells. The X-ray
      structures of homologous viruses complexed with N-terminal glycoproteins suggest
      that the BC and HI loops of the viral coat are determinant for binding and
      thereby infection of the host cell. The large size of the viral coat precludes it
      from common biophysical and small molecule screening studies. Hence, we sought to
      develop a smaller protein template incorporating the identified binding loops of
      the BK viral coat in a manner that adequately mimics the binding characteristics
      of the BK virus coat protein to cells. Such a mimic may serve as a tool for the
      identification of inhibitors of BK viral progression. Herein, we report the
      design and characterization of a reduced-size and soluble template derived from a
      four-helix protein-TM1526 of Thermatoga maritima archaea bacteria-which maintains
      the topological display of the BC and HI loops as found in the viral coat
      protein, VP1, of BKV. We demonstrate that the GT1b and GD1b sialogangliosides,
      which bind to the VP1 of BKV, also associate with our BKV template. Employing a
      GFP-tagged template, we show host cell association that is dose dependent and
      that can be reduced by neuraminidase treatment. These data demonstrate that the
      BKV template mimics the host cell binding observed for the wild-type virus coat
      protein VP1.

PMID- 23002933
TI  - New therapeutic advances in CNS injury and repair.
AB  - The 9th Global College of Neuroprotection and Neuroregeneration annual meeting
      was held in cooperation with the 5th International Association of
      Neurorestoratology and the 4th International Spinal Cord Injury Treatment and
      Trial Symposium in the beautiful city of Xi'an, Shaanxi Province, China, between
      4 and 7 May 2012. This trilateral conference was held in the pleasing ambience of
      the Sofitel Hotel Complex in Renmin Square, Xi'an. Top Chinese government
      dignitaries including the National Deputy Health Minister, Vice Governor of
      Shaanxi Province, Vice President of Xi'an Jiaotong University and Party Secretary
      of the Medical Association inaugurated the congress. More than 1000 delegates
      from across the world, including approximately 600 medical researchers from
      China, participated in this meeting. The theme of this meeting was
      'neurorestoration and neurorepair' using stem cell treatment, antibodies and
      pharmacotherapy, as well as nanomedicine and neurorehabilitation. Preclinical and
      clinical research was presented and discussed. Use of nanomedicine to enhance
      neurorepair or diagnosis of neurological diseases in clinical situations was the
      new attraction in this trilateral meeting. More than 50 leading experts in
      neuroprotection and neurorestoratology presented their cutting edge research in
      the area. New features included the Youth Forum in which 12 young scientists
      presented their innovative results, and more than 30 platform presentations were
      included. Thus, the trilateral conference of the Global College of
      Neuroprotection and Neuroregeneration, the International Association of
      Neurorestoratology and the International Spinal Cord Injury Treatment and Trial
      Symposium was extremely successful from both the scientific and social
      perspectives.

PMID- 23002934
TI  - Statin use and lipid profile in relation to safety and functional outcome after
      thrombolysis in ischemic stroke.
AB  - Statins are widely used in the primary and secondary prevention of cardiovascular
      disease and prevent first and recurrent ischemic strokes mainly because of their
      lipid-lowering effect. However, they also have pleiotropic effects and might be
      neuroprotective in acute ischemic stroke. Improved functional outcome in patients
      with acute ischemic stroke treated with intravenous thrombolysis tissue
      plasminogen activator has been proposed, but not confirmed by other studies.
      Furthermore, some studies showed an increased risk of symptomatic intracranial
      hemorrhage in statin users. The article being evaluated presents a large
      observational cohort of acute ischemic stroke patients treated with intravenous
      tissue plasminogen activator and showed no association between statin use or
      lipid profiles and functional outcome or risk of symptomatic intracranial
      hemorrhage. The results of this article are discussed in the context of previous
      published studies.

PMID- 23002935
TI  - Combined assessment of midbrain hyperechogenicity, hyposmia and motor asymmetry
      improves diagnostic accuracy in early Parkinson's disease.
AB  - The differential diagnosis of Parkinsonian syndromes can be challenging,
      particularly in early disease stages, when overlapping clinical signs and
      symptoms may lead to erroneous classification. However, an early differentiation
      between Parkinson's disease (PD) and other diseases causing Parkinsonism is
      crucial for prognostic and therapeutic reasons and is essential for clinical
      research. In a recent study, Busse et al. investigated the diagnostic utility of
      a set of tests to improve diagnostic differentiation between PD, essential tremor
      and other Parkinsonian disorders. The authors studied a total of 632 patients
      divided into a retrospective (n = 517) and a prospective (n = 115) group.
      Diagnostic anchors were based on clinical criteria. Combining midbrain
      hyperechogenicity, hyposmia and motor asymmetry increased specificity and
      positive predictive value for diagnosis of PD up to 98% at the expense of
      sensitivity, whereas two features provided 91% sensitivity with 77% specificity.
      The results of this study further support the diagnostic utility of transcranial
      sonography in diagnosing PD.

PMID- 23002936
TI  - New approaches to bedside monitoring in stroke.
AB  - Stroke is a common, potentially devastating disease with potential high morbidity
      and mortality. Recognition at the onset of acute ischemic stroke is pivotal to
      changing outcomes such as intravenous thrombolysis. Stroke monitoring is a
      burgeoning field with various methods described and newer devices that aid in
      detecting acute or worsening ischemia that can lead to improved bedside and
      intensive care unit management. This article describes various methods of bedside
      stroke monitoring including newer techniques of intracranial pressure monitoring
      using the pressure reactivity index and compensatory reserve index to detect
      changes in autoregulatory states, noninvasive intracranial pressure monitoring,
      quantitative EEG with alpha-delta ratio, transcranial Doppler, methods of
      arteriovenous brain oxygen monitoring such as jugular venous oxygen and near
      infrared spectroscopy, invasive brain oxygen probes such as LicoxTM (brain tissue
      O2), cerebral blood flow probe (CBF HemedexTM) and cerebral microdialysis.

PMID- 23002937
TI  - Role for cytotoxic chemotherapy in patients with recurrent glioblastoma
      progressing on bevacizumab: a retrospective case series.
AB  - One hundred patients, aged 36-84 years (median 62 years) with recurrent
      glioblastoma (GBM), were treated previously with surgery, concurrent radiotherapy
      and temozolomide and postradiotherapy temozolomide followed by single-agent
      bevacizumab (BEV) at either first (60 patients) or second recurrence (40
      patients). Patients were then treated following progression on BEV only with BEV
      and carboplatin (75 patients), cyclophosphamide (15 patients) or BCNU (ten
      patients; BEV+). Three hundred and sixteen treatment cycles (median: 2; range: 1
      9) were administered of BEV+. There were 74 grade 3 adverse events in 29 patients
      (29%) and 20 grade 4 adverse events in ten patients (10%). Following 2 months of
      BEV+, 60 patients (60%) demonstrated progressive disease and discontinued
      therapy. Forty patients (40%) had neuroradiographic stable disease. Survival
      ranged from 1 to 12 months (median: 4 months). Median and 6-month progression
      free survival was 2.5 months and 5%, respectively. BEV plus a cytotoxic
      chemotherapy demonstrated limited efficacy in BEV-refractory GBM and emphasizes
      an unmet need in neuro-oncology in adults with BEV-refractory GBM.

PMID- 23002938
TI  - The intolerance of uncertainty construct in the context of anxiety disorders:
      theoretical and practical perspectives.
AB  - Modern anxiety disorder models implicitly include intolerance of uncertainty (IU)
      as a critical component for the development and maintenance of these pervasive
      social and economic concerns. IU represents, at its core, fear of the unknown - a
      long-recognized, deep-seated fear identified in normative and pathological
      samples. Indeed, the intrinsic nature of IU can be argued as evolutionarily
      supported, a notion buttressed by initial biophysiological evidence from
      uncertainty-related research. Originally thought to be specific to generalized
      anxiety disorder, recent research has clearly demonstrated that IU is a broad
      transdiagnostic dispositional risk factor for the development and maintenance of
      clinically significant anxiety. The available evidence suggests that theorists,
      researchers and clinicians may benefit from explicitly incorporating IU into
      models, research designs, case conceptualizations and as a treatment target.

PMID- 23002939
TI  - Stroke rehabilitation using noninvasive cortical stimulation: motor deficit.
AB  - Noninvasive cortical stimulation (NICS) has been used during the acute, postacute
      and chronic poststroke phases to improve motor recovery in stroke patients having
      upper- and/or lower-limb paresis. This paper reviews the rationale for using the
      different NICS modalities to promote motor stroke rehabilitation. The changes in
      cortical excitability after stroke and the possible mechanisms of action of
      cortical stimulation in this context are outlined. A number of open and placebo
      controlled trials have investigated the clinical effect of repetitive
      transcranial magnetic stimulation (rTMS) or transcranial direct current
      stimulation (tDCS) of the primary motor cortex in patients with motor stroke.
      These studies attempted to improve motor performance by increasing cortical
      excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal
      tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via
      low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the
      inhibition exerted by the unaffected hemisphere on the affected hemisphere and to
      then restore a normal balance of interhemispheric inhibition. All these NICS
      techniques administered alone or in combination with various methods of
      neurorehabilitation were found to be safe and equally effective at the short term
      on various aspects of poststroke motor abilities. However, the long-term effect
      of NICS on motor stroke needs to be further evaluated before considering the use
      of such a technique in the daily routine management of stroke.

PMID- 23002940
TI  - Stroke rehabilitation using noninvasive cortical stimulation: aphasia.
AB  - Poststroke aphasia results from the lesion of cortical areas involved in the
      motor production of speech (Broca's aphasia) or in the semantic aspects of
      language comprehension (Wernicke's aphasia). Such lesions produce an important
      reorganization of speech/language-specific brain networks due to an imbalance
      between cortical facilitation and inhibition. In fact, functional recovery is
      associated with changes in the excitability of the damaged neural structures and
      their connections. Two main mechanisms are involved in poststroke aphasia
      recovery: the recruitment of perilesional regions of the left hemisphere in case
      of small lesion and the acquisition of language processing ability in homotopic
      areas of the nondominant right hemisphere when left hemispheric language
      abilities are permanently lost. There is some evidence that noninvasive cortical
      stimulation, especially when combined with language therapy or other therapeutic
      approaches, can promote aphasia recovery. Cortical stimulation was mainly used to
      either increase perilesional excitability or reduce contralesional activity based
      on the concept of reciprocal inhibition and maladaptive plasticity. However,
      recent studies also showed some positive effects of the reinforcement of neural
      activities in the contralateral right hemisphere, based on the potential
      compensatory role of the nondominant hemisphere in stroke recovery.

PMID- 23002941
TI  - Stroke rehabilitation using noninvasive cortical stimulation: hemispatial
      neglect.
AB  - The rehabilitation of neuropsychological sequels of cerebral stroke such as
      hemispatial neglect by noninvasive cortical stimulation (NICS) attracts
      increasing attention from the scientific community. The NICS techniques include
      primarily repetitive transcranial magnetic stimulation (rTMS) and transcranial
      direct current stimulation (tDCS). They are based on the concept of either
      reactivating a hypoactive cortical region affected by the stroke (the right
      hemisphere in case of neglect) or reducing cortical hyperactivity of the
      corresponding cortical region in the contralateral hemisphere (the left
      hemisphere). In the studies published to date on the topic of neglect
      rehabilitation, rTMS was used to inhibit the left parietal cortex and tDCS to
      either activate the right or inhibit the left parietal cortex. Sham-controlled
      NICS studies assessed short-term effects, whereas long-term effects were only
      assessed in noncontrolled rTMS studies. Further controlled studies of large
      series of patients are necessary to determine the best parameters of stimulation
      (including the optimal cortical target location) according to each subtype of
      neglect presentation and to the time course of stroke recovery. To date, even if
      there are serious therapeutic perspectives based on imaging data and experimental
      studies, the evidence is not compelling enough to recommend any particular NICS
      protocol to treat this disabling condition in clinical practice.

PMID- 23002942
TI  - Issues and controversies surrounding the diagnosis and treatment of social
      anxiety disorder.
AB  - Although much has been learned about social anxiety disorder (SAD) in recent
      decades, many questions and controversies surrounding its diagnosis and treatment
      have remained. Similar to the state of affairs with other psychiatric disorders,
      no clear pathophysiology has been identified for SAD, and the question of where
      to draw the line between shyness, SAD and even avoidant personality disorder
      continues to be debated. Much of the evidence to date suggests that among persons
      with SAD, it is under-recognized and undertreated; however, other researchers
      contend that it may be overdiagnosed in some individuals. Questions also remain
      as to how best treat these individuals, such as with pharmacotherapy,
      psychotherapy or a combination of the two. The aim of this review is to provide
      an overview of the controversies related to the diagnosis and treatment of SAD.
      In addition, suggestions for future research are provided that could perhaps
      clarify these remaining questions, such as maximizing treatment efficacy by
      targeting broader outcomes such as quality of life and addressing common
      comorbidities that occur with SAD.

PMID- 23002946
TI  - Did she jump because she was the big sister or because the trampoline was safe?
      Causal inference and the development of social attribution.
AB  - Children rely on both evidence and prior knowledge to make physical causal
      inferences; this study explores whether they make attributions about others'
      behavior in the same manner. A total of one hundred and fifty-nine 4- and 6-year
      olds saw 2 dolls interacting with 2 activities, and explained the dolls' actions.
      In the person condition, each doll acted consistently across activities, but
      differently from each other. In the situation condition, the two dolls acted
      differently for each activity, but both performed the same actions. Both age
      groups provided more "person" explanations (citing features of the doll) in the
      person condition than in the situation condition. In addition, 6-year-olds showed
      an overall bias toward "person" explanations. As in physical causal inference,
      social causal inference combines covariational evidence and prior knowledge.

PMID- 23002944
TI  - Post-traumatic stress disorder as a comorbidity: impact on disease outcomes.
AB  - Post-traumatic stress disorder (PTSD) is associated with many psychiatric and
      nonpsychiatric comorbidities. Growing evidence suggests that PTSD as a
      comorbidity may impair drug adherence, quality of life and sleep quality, as well
      as increase rehospitalization rates, disease relapses, intensity of symptoms,
      morbidity and mortality. The aim of this article is to examine the literature
      regarding the effects of PTSD comorbidity on physical and mental health.

PMID- 23002947
TI  - Does feeding tube insertion and its timing improve survival?
AB  - OBJECTIVES: To examine survival with and without a percutaneous endoscopic
      gastrostomy (PEG) feeding tube using rigorous methods to account for selection
      bias and to examine whether the timing of feeding tube insertion affected
      survival. DESIGN: Prospective cohort study. SETTING: All U.S. nursing homes
      (NHs). PARTICIPANTS: Thirty-six thousand four hundred ninety-two NH residents
      with advanced cognitive impairment from dementia and new problems eating studied
      between 1999 and 2007. MEASUREMENTS: Survival after development of the need for
      eating assistance and feeding tube insertion. RESULTS: Of the 36,492 NH residents
      (88.4% white, mean age 84.9, 87.4% with one feeding tube risk factor), 1,957
      (5.4%) had a feeding tube inserted within 1 year of developing eating problems.
      After multivariate analysis correcting for selection bias with propensity score
      weights, no difference was found in survival between the two groups (adjusted
      hazard ratio (AHR) = 1.03, 95% confidence interval (CI) = 0.94-1.13). In
      residents who were tube-fed, the timing of PEG tube insertion relative to the
      onset of eating problems was not associated with survival after feeding tube
      insertion (AHR = 1.01, 95% CI = 0.86-1.20, persons with a PEG tube inserted
      within 1 month of developing an eating problem versus later (4 months)
      insertion). CONCLUSION: Neither insertion of PEG tubes nor timing of insertion
      affect survival.

PMID- 23002943
TI  - Exploring exercise as an avenue for the treatment of anxiety disorders.
AB  - Anxiety disorders constitute a significant public health problem. Current gold
      standard treatments are limited in their effectiveness, prompting the
      consideration of alternative approaches. In this review, we examine the evidence
      for exercise as an intervention for anxiety disorders. This evidence comes from
      population studies, studies of nonclinical anxiety reduction, as well as a
      limited number of studies of clinically anxious individuals. All of these studies
      provide converging evidence for consistent beneficial effects of exercise on
      anxiety, and are consistent with a variety of accounts of the mechanism of
      anxiety reduction with exercise. Further study of clinical populations is
      encouraged, as are studies of the mechanism of change of exercise interventions,
      which have the potential to help refine exercise intervention strategies.
      Likewise, studies that identify moderators of treatment efficacy will assist
      clinicians in deciding how and for whom to prescribe exercise.

PMID- 23002949
TI  - Identification of the narrow lumen of the ureter using a Fogarty catheter during
      laparoscopic pyeloplasty.
AB  - It is difficult to identify the narrow sites of the ureter from the outside while
      carrying out laparoscopic pyeloplasty in patients with ureteropelvic junction
      obstruction. We developed and named a new method, the Fogarty test, to identify
      the narrow sites of the ureter using a Fogarty catheter. A 4- to 5-Fr Fogarty
      catheter was inserted through an incision in the pelvis to the proximal ureter,
      inflated with air and withdrawn gently to determine resistance. The narrow lumen
      of the ureter was identified under direct vision and spatulated by laparoscopic
      scissors. This procedure was carried out repeatedly until the ureter was fully
      spatulated. By using the Fogarty test, we can visualize the narrow position and
      length of the ureter under direct vision, and confirm whether it is fully
      spatulated or not. This technique is very simple and easy to carry out. We
      believe it is useful for sufficient spatulation of intrinsic ureteral stricture,
      especially in patients where multiple narrow sites exist.

PMID- 23002948
TI  - Modeling seroadaptation and sexual behavior among HIV+ study participants with a
      simultaneously multilevel and multivariate longitudinal count model.
AB  - Longitudinal behavioral intervention trials to reduce HIV transmission risk
      collect complex multilevel and multivariate data longitudinally for each subject
      with important correlation structures across time, level, and variables.
      Accurately assessing the effects of these trials are critical for determining
      which interventions are effective. Both numbers of partners and numbers of sex
      acts with each partner are reported at each time point. Sex acts with each
      partner are further differentiated into protected and unprotected acts with
      correspondingly differing risks of HIV/STD transmission. These trials generally
      also have eligibility criteria limiting enrollment to participants with some
      minimal level of risky sexual behavior tied directly to the outcome of interest.
      The combination of these factors makes it difficult to quantify sexual behaviors
      and the effects of intervention. We propose a multivariate multilevel count model
      that simultaneously models the number of partners, acts within partners, and
      accounts for recruitment eligibility. Our methods are useful in the evaluation of
      intervention trials and provide a more accurate and complete model for sexual
      behavior. We illustrate the contributions of our model by examining seroadaptive
      behavior defined as risk reducing behavior that depends on the serostatus of the
      partner. Several forms of seroadaptive risk reducing behavior are quantified and
      distinguished from nonseroadaptive risk reducing behavior.

PMID- 23002950
TI  - Spontaneous cessation and recurrence of massive uterine bleeding can occur in
      uterine artery pseudoaneurysm after laparoscopically assisted myomectomy.
AB  - A uterine artery pseudoaneurysm (UAP) is a rare but life-threatening complication
      that can occur after gynecologic surgery. Herein, we present a case of a 38-year
      old woman who presented with massive uterine bleeding one month after a
      laparoscopically assisted myomectomy. Although the bleeding ceased spontaneously,
      a massive hemorrhage reoccurred three weeks thereafter, and a ruptured perfusion
      sac at the right uterine artery was identified by computed tomography angiography
      and ultrasonography. The patient was treated with transfemoral catheter
      embolization of the right uterine artery, and complete resolution of the UAP was
      successfully obtained. Our case suggests that a UAP may be a cause of unexplained
      repetitive metrorrhagia after myomectomy.

PMID- 23002951
TI  - Post-sleep inertia performance benefits of longer naps in simulated nightwork and
      extended operations.
AB  - Operational settings involving shiftwork or extended operations require periods
      of prolonged wakefulness, which in conjunction with sleep loss and circadian
      factors, can have a negative impact on performance, alertness, and workplace
      safety. Napping has been shown to improve performance and alertness after periods
      of prolonged wakefulness and sleep loss. Longer naps may not only result in
      longer-lasting benefits but also increase the risk of sleep inertia immediately
      upon waking. The time course of performance after naps of differing durations is
      thus an important consideration in weighing the benefits and risks of napping in
      workplace settings. The objective of this study was to evaluate the effectiveness
      of nap opportunities of 20, 40, or 60 min for maintaining alertness and
      performance 1.5-6 h post-nap in simulated nightwork (P1) or extended operations
      (P2). Each protocol included 12 participants in a within-subjects design in a
      controlled laboratory environment. After a baseline 8 h time-in-bed, healthy
      young males (P1 mean age 25.1 yr; P2 mean age 23.2 yr) underwent either ~ 20 h
      (P1) or ~ 30 h (P2) of sleep deprivation on four separate occasions, followed by
      nap opportunities of 0, 20, 40, and 60 min. Sleep on the baseline night and
      during the naps was recorded polysomnographically. During the nap opportunities,
      sleep onset latency was short and sleep efficiency was high. A greater proportion
      of slow-wave sleep (SWS) was obtained in nap opportunities of 40 and 60 min
      compared with 20 min. Rapid eye movement (REM) sleep occurred infrequently. A
      subjective sleepiness rating (Karolinska Sleepiness Scale, KSS), 2-Back Working
      Memory Task (WMT), and Psychomotor Vigilance Task (PVT) were completed 1.5, 2,
      2.5, 3, 4, 5, and 6 h post-nap. The slowest 10% of PVT responses were
      significantly faster after 40 and 60 min naps compared with a 20 min (P1) or no
      (P2) nap. There were significantly fewer PVT lapses after 40 and 60 min naps
      compared with no nap (P2), and after 60 min naps compared with 20 min naps (P1).
      Participants felt significantly less sleepy and made more correct responses and
      fewer omissions on the WMT after 60 min naps compared with no nap (P2).
      Subjective sleepiness and WMT performance were not related to the amount of nap
      time spent in SWS. However, PVT response speed was significantly slower when time
      in SWS was <10 min compared with 20-29.9 min. In conclusion, in operationally
      relevant scenarios, nap opportunities of 40 and 60 min show more prolonged
      benefits 1.5-6 h post-nap, than a 20 min or no nap opportunity. Benefits were
      more apparent when the homeostatic pressure for sleep was high and post-nap
      performance testing occurred across the afternoon (P2). For sustained improvement
      in cognitive performance, naps of 40-60 min are recommended.

PMID- 23002952
TI  - Investigation of developmental toxicity and teratogenicity of antiemetics on rat
      embryos cultured in vitro.
AB  - In this study, we aimed to investigate and compare the direct toxic and
      teratogenic effects of dimenhydrinate, metoclopramide and trimethobenzamide HCl,
      antiemetic drugs on embryonic growth and development in cultured rat embryos.
      Embryos were explanted on day 9.5 of gestation and cultured. Whole rat serum was
      used as a culture medium for the control group while different concentrations of
      dimenhydrinate (2.5-20 MUg/ml), metoclopramide (10-50 MUg/ml) and
      trimethobenzamide HCl (25-100 MUg/ml) were added to serum for the experimental
      groups. Effects of antiemetics on embryonic developmental parameters were
      compared, and embryos were evaluated for the presence of any malformations. Also,
      the total DNA was extracted from the cells to determine the fragmentation of
      nuclear DNA of embryonic cells. Compared with the control embryos, the
      antiemetics significantly decreased all growth and developmental parameters dose
      dependently. There was no difference regarding the fragmentation of nuclear DNA
      of the all used agents and controls. Amongst the agents, trimethobenzamide HCl
      was found to have more toxic and teratogenic potential, and metoclopramide
      appears to be the least toxic antiemetic and therefore could be more safely used
      and might be preferred for the treatment of nausea and vomiting in pregnancy.

PMID- 23002953
TI  - Impact of tamoxifen on amount of fibroglandular tissue, background parenchymal
      enhancement, and cysts on breast magnetic resonance imaging.
AB  - The objective of this study was to evaluate the impact of tamoxifen treatment on
      amount of fibroglandular tissue (FGT), background parenchymal enhancement (BPE),
      and cysts on breast MRI. Retrospective search identified 96 women with breast
      cancer who had a breast MRI both before and during adjuvant tamoxifen therapy
      between 2002 and 2008. After exclusion of all irradiated breasts, 88 women were
      eligible. Two readers blinded to tamoxifen treatment status independently rated
      level of BPE, amount of FGT, and cysts using a 4-point categorical scale: BPE-
      Minimal, Mild, Moderate, Marked; FGT--Fatty, Scattered, Heterogeneously Dense
      (HD), Dense; Cysts--Minimal, Mild, Moderate, Marked. A consensus interpretation
      was reached in cases of disagreement. During tamoxifen, there was a significant
      shift from higher to lower degree BPE, cysts, and FGT compared with before
      tamoxifen. BPE, cysts and FGT decreased in 68% (60/88), 38% (33/88), and 40%
      (35/88) of women during tamoxifen (p<0.001 for all measures). After the exclusion
      of all cases with minimal BPE, cysts, or FGT on the pre-tamoxifen MRI, the
      percentage of women demonstrating a decrease in these factors increased to 81%
      (60/74), 77% (33/43), and 41% (35/86), respectively. Exclusion of patients
      treated with chemotherapy did not substantially change these results. The
      percentage of women with decreases in FGT and cysts increased with greater
      duration on tamoxifen, whereas decreases in BPE were detected early in treatment
      (<90 days) and did not change substantially with longer duration on tamoxifen. A
      significant association exists between treatment with tamoxifen and decreases in
      BPE, cysts, and FGT on breast MRI.

PMID- 23002954
TI  - Multiple host feeding in Glossina palpalis gambiensis and Glossina tachinoides in
      southeast Mali.
AB  - Changes in agricultural practices and the resulting extinction of wildlife have
      led to the reduction or disappearance of savannah tsetse species. Riparian tsetse
      such as Glossina palpalis gambiensis Vanderplank 1949 and Glossina tachinoides
      Westwood 1850 (Diptera: Glossinidae) continue to persist in peridomestic sites,
      transmitting trypanosomiasis. At present, little is known about interspecies
      differences in feeding behaviour in these two species in southeast Mali, or of
      the phenomenon of multiple bloodmeals. To study these topics, 279 samples of G.
      p. gambiensis and G. tachinoides containing host DNA, caught in the Sikasso
      region between November 2008 and April 2009, were analysed by applying host
      species-specific primers and sequencing. Human accounted for > 66% of G. p.
      gambiensis bloodmeals, whereas G. tachinoides contained in equal parts DNA of
      human, cattle or both, showing a significantly higher proportion of multiple host
      use. Further, the trypanosome infection rate was found to be three-fold higher in
      G. tachinoides. Logistic regression analysis revealed double-feeding and
      infection to be independent of one another, but showed infection to be correlated
      with engorgement in G. p. gambiensis and female sex in G. tachinoides. Enhanced
      host-seeking activities paired with the high trypanosome infection rate found in
      G. tachinoides would indicate that this species has a higher vectorial capacity
      than G. p. gambiensis.

PMID- 23002955
TI  - Potential negative effects of perspective-taking efforts in the context of close
      relationships: increased bias and reduced satisfaction.
AB  - Three experiments demonstrated that trying to appreciate a close other's unique
      point of view (imagine-other perspective taking) increases the extent to which
      individuals overestimate their own transparency to the close other, that is, how
      many of their values, preferences, traits, and feelings are readily apparent to
      him or her. Trying to be objective and pay careful attention to cues from a close
      other, which inhibits perspective taking, instead had the opposite effect.
      Mediation analyses suggested that increased focus on the self as an object of
      evaluation contributed to the positive effect of imagine-other perspective taking
      on perceived transparency, and decreased focus on the self as an object of
      evaluation contributed to the negative effect of trying to be objective on these
      judgments. These effects on perceived transparency had important implications for
      relationship well-being: Enhanced perceived transparency of negative feelings
      prompted by imagine-other perspective taking during a back-and-forth exchange
      with a romantic partner led to systematic discrepancies between individuals' own
      and their partner's experience of the exchange and reduced relationship
      satisfaction; trying to be objective instead reduced perceived transparency and
      thereby increased satisfaction. Notably, initial closeness with another person
      enhanced rather than tempered the egocentric effects of perspective taking. Taken
      together, these results suggest that positive motivations to nurture a close
      relationship and be sensitive to a loved one might sometimes be better channeled
      toward paying closer attention to his or her behavior than toward perspective
      taking.

PMID- 23002957
TI  - Retraction. Visual perspective influences the use of metacognitive information in
      temporal comparisons.

PMID- 23002956
TI  - Inventing racist roads not taken: the licensing effect of immoral counterfactual
      behaviors.
AB  - Six experiments examined how people strategically use thoughts of foregone
      misdeeds to regulate their moral behavior. We tested 2 hypotheses: 1st, that
      people will feel licensed to act in morally dubious ways when they can point to
      immoral alternatives to their prior behavior, and 2nd, that people made to feel
      insecure about their morality will exaggerate the extent to which such
      alternatives existed. Supporting the 1st hypothesis, when White participants
      could point to racist alternatives to their past actions, they felt they had
      obtained more evidence of their own virtue (Study 1), they expressed less racial
      sensitivity (Study 2), and they were more likely to express preferences about
      employment and allocating money that favored Whites at the expense of Blacks
      (Study 3). Supporting the 2nd hypothesis, White participants whose security in
      their identity as nonracists had been threatened remembered a prior task as
      having afforded more racist alternatives to their behavior than did those who
      were not threatened. This distortion of the past involved overestimating the
      number of Black individuals they had encountered on the prior task (Study 4) and
      exaggerating how stereotypically Black specific individuals had looked (Studies 5
      and 6). We discuss implications for moral behavior, the motivated rewriting of
      one's moral history, and how the life unlived can liberate people to lead the
      life they want.

PMID- 23002958
TI  - A review of recent patents on the protozoan parasite HSP90 as a drug target.
AB  - Diseases caused by protozoan parasites are still an important health problem.
      These parasites can cause a wide spectrum of diseases, some of which are severe
      and have high morbidity or mortality if untreated. Since they are still
      uncontrolled, it is important to find novel drug targets and develop new
      therapies to decrease their remarkable social and economic impact on human
      societies. In the past years, human HSP90 has become an interesting drug target
      that has led to a large number of investigations both at state organizations and
      pharmaceutical companies, followed by clinical trials. The finding that HSP90 has
      important biological roles in some protozoan parasites like Plasmodium spp,
      Toxoplasma gondii and trypanosomatids has allowed the expansion of the results
      obtained in human cancer to these infections. This review summarizes the latest
      important findings showing protozoan HSP90 as a drug target and presents three
      patents targeting T. gondii, P. falciparum and trypanosomatids HSP90. 

PMID- 23002959
TI  - Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver
      fibrosis.
AB  - Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the
      therapy of diseases. Exosomes excreted from MSCs can reduce myocardial
      ischemia/reperfusion damage and protect against acute tubular injury. However,
      whether MSC-derived exosomes can relieve liver fibrosis and its mechanism remain
      unknown. Previous work showed that human umbilical cord-MSCs (hucMSCs)
      transplanted into acutely injured and fibrotic livers could restore liver
      function and improve liver fibrosis. In this study, it was found that
      transplantation of exosomes derived from hucMSC (hucMSC-Ex) reduced the surface
      fibrous capsules and got their textures soft, alleviated hepatic inflammation and
      collagen deposition in carbon tetrachloride (CCl4)-induced fibrotic liver. hucMSC
      Ex also significantly recovered serum aspartate aminotransferase (AST) activity,
      decreased collagen type I and III, transforming growth factor (TGF)-beta1 and
      phosphorylation Smad2 expression in vivo. In further experiments, we found that
      epithelial-to-mesenchymal transition (EMT)-associated markers E-cadherin-positive
      cells increased and N-cadherin- and vimentin-positive cells decreased after
      hucMSC-Ex transplantation. Furthermore, the human liver cell line HL7702
      underwent typical EMT after induction with recombinant human TGF-beta1, and then
      hucMSC-Ex treatment reversed spindle-shaped and EMT-associated markers expression
      in vitro. Taken together, these results suggest that hucMSC-Ex could ameliorate
      CCl4-induced liver fibrosis by inhibiting EMT and protecting hepatocytes. This
      provides a novel approach for the treatment of fibrotic liver disease.

PMID- 23002960
TI  - Systemic inflammation associated with severe intestinal injury in extremely low
      gestational age newborns.
AB  - To define the role of systemic inflammation in infants with intestinal
      perforation (IP) and necrotizing enterocolitis (NEC), we measured 25 blood
      protein concentrations on days 1, 7 and 14 in 939 infants born before 28 weeks'
      gestation. On days 7 and 14, infants with NEC had elevated levels of C-reactive
      protein (CRP), serum amyloid A (SAA), IL-6 and IL-8. Infants with IP had elevated
      levels of CRP and insulin growth factor binding protein-1 on day 7 and elevated
      CRP, SAA, TNF-receptor-2 and matrix metalloproteinase-9 levels on day 14. A
      better understanding of systemic inflammation might help prevent and treat these
      disorders.

PMID- 23002961
TI  - Development and validation of a medium-throughput electrophysiological assay for
      KCNQ2/3 channel openers using QPatch HT.
AB  - The KCNQ2/3 channel has emerged as a drug target for a number of neurological
      disorders including pain and epilepsy. Known KCNQ2/3 openers have effects on two
      distinct biophysical properties of the channel: (1) a hyperpolarizing shift in
      the voltage dependence of channel activation (V(1/2)), and (2) an increase in
      channel open probability or peak whole-cell current. The current high-throughput
      screening assays for KCNQ2/3 openers measure changes of channel activity at sub
      peak conductances and the output measure is a combination of effects on V(1/2)
      shift and peak current. Here, we describe a medium-throughput
      electrophysiological assay for screening KCNQ2/3 openers using the QPatch HT
      platform. We employed a double-pulse protocol that measures the shift in V(1/2)
      and the change in current amplitude at peak conductance voltage. Retigabine along
      with novel KCNQ2/3 openers were evaluated in this assay. Three classes of KCNQ2/3
      openers were identified based on the hyperpolarizing shift in V(1/2) and the
      change in peak current. All three classes of compounds caused a hyperpolarizing
      shift in V(1/2), but they were differentiated by their respective effects on peak
      current amplitude (increase, decrease, or only modestly affecting peak current
      amplitude). KCNQ2/3 blockers were also identified with this assay. These
      compounds blocked currents without affecting voltage-dependent activation. In
      summary, we have developed a medium-throughput assay that can reliably detect
      changes in the biophysical properties of the KCNQ2/3 channel, V(1/2), and peak
      current amplitude, and therefore may serve as a reliable assay to evaluate
      KCNQ2/3 openers and blockers.

PMID- 23002962
TI  - Prior publication: extended abstracts, proceedings articles, preprint servers,
      and the like.

PMID- 23002964
TI  - Improving influenza vaccines.

PMID- 23002965
TI  - Influenza vaccines and immunopathology.

PMID- 23002966
TI  - The role of vaccines and vaccination in high pathogenicity avian influenza
      control and eradication.

PMID- 23002967
TI  - Reproducibility of assays for influenza vaccine immunogenicity determination:
      progress towards consistency.

PMID- 23002969
TI  - Pneumococcal 13-valent conjugate vaccine for the prevention of invasive
      pneumococcal disease in children and adults.
AB  - Pneumococcal disease remains a global problem despite the availability of
      effective conjugate vaccines. The 13-valent pneumococcal conjugate vaccine
      (PCV13) extends the valency of PCV7 by including six additional serotypes highly
      associated with invasive pneumococcal disease (IPD). Comparisons between PCV13
      and PCV7 or the pneumococcal polysaccharide vaccine have established
      noninferiority of PCV13 for both safety and immunogenicity profiles for use in
      children and adults, respectively. At the end of 2011, PCV13 had been approved
      and launched in 104 countries worldwide, with 54 including the vaccine in their
      pediatric national immunization program. Surveillance data from early adopters of
      PCV13 has indicated reductions are occurring in both overall IPD and IPD caused
      by the six non-PCV7 serotypes; early reports of serotype replacement in carriage
      are also emerging. While serotype replacement for PCV7 was observed to varying
      degrees for both carriage and disease, the extent to which this will occur for
      PCV13 is yet to be determined.

PMID- 23002970
TI  - Usefulness of influenza vaccination during pregnancy to mothers and young
      infants.
AB  - As pregnant women are at increased risk of influenza infection and influenza
      related complications, immunization with inactivated influenza vaccine during the
      influenza season is recommended. Vaccination during pregnancy is considered to
      provide benefits for both the mothers and their young infants. In 2009, the novel
      influenza A (H1N1) virus was reported worldwide to be the cause of a widespread
      outbreak of acute febrile respiratory illness. The efficacy and efficiency of
      monovalent vaccine against 2009 H1N1 influenza virus during pregnancy has already
      been confirmed in several studies. This article provides further useful
      information regarding the persistence of maternal antibodies and the
      transplacental transfer of antibodies following vaccination by comparison with
      natural influenza infection.

PMID- 23002971
TI  - Perspectives on replication-incompetent nasal influenza virus vaccines.
AB  - Influenza is an emerging as well as resurging contagious disease with a worldwide
      impact on public health. Although broad administration of the licensed influenza
      virus (IFV) vaccines has mitigated the disease in many countries over the years,
      there are intrinsic problems associated with them. The study under evaluation
      reports that a novel PB2-knockout nonreplicating nasal IFV vaccine has been
      generated with the capacity to confer protection of mice against live IFV
      challenges. Moreover, an exogenous gene expressed from the bioengineered PB2
      knockout IFV could elicit an immune response against the exogenous protein,
      showing its potential to deliver transgenes as a vector. The risk-benefit ratio
      of this new influenza vaccine vector is discussed.

PMID- 23002972
TI  - Safety of seasonal influenza and influenza A (H1N1) 2009 monovalent vaccines in
      pregnancy.
AB  - Inactivated influenza vaccines have been given to pregnant women since 1964.
      Since 2004, the Advisory Committee on Immunization Practices has recommended that
      pregnant women receive trivalent inactivated influenza vaccine at any time during
      pregnancy. Studies conducted before 2009 did not identify any safety concerns
      after trivalent inactivated influenza vaccine in mothers or their infants. During
      the 2009-2010 influenza A (H1N1) influenza vaccination program, several
      monitoring systems were established or enhanced to assess whether adverse events
      were associated with H1N1 2009 monovalent vaccines (2009 H1N1 influenza
      vaccines). Data from these systems did not identify any safety concerns in
      pregnant women who received 2009 H1N1 influenza vaccines or their infants.
      Although live attenuated influenza vaccines are not recommended in pregnant
      women, a small number of studies have not shown any safety concern among pregnant
      women or their infants who were inadvertently exposed to these vaccines. This
      review summarizes US and international safety data for influenza vaccines in
      pregnant women with an emphasis on 2009 H1N1 influenza vaccines.

PMID- 23002973
TI  - Universal influenza vaccine: the holy grail?
AB  - Influenza vaccines have been available since the 1950s and have seen increasingly
      wide use as public health authorities expanded recommendations. Recent events
      including shortages and avian influenza outbreaks have renewed interest in
      influenza vaccines, particularly improved vaccines.

PMID- 23002974
TI  - Clinical, scientific and ethnographic studies of influenza in quarantine.
AB  - From the time of the Spanish influenza pandemic in 1918 to the present seclusion
      of volunteers in quarantine units, either modified hotels, Phase I units or
      specially constructed clinics, have been key in investigating new vaccines and
      antivirals. Carefully selected healthy, young volunteers undergo a 10-12-day
      sojourn under intense medical supervision. Clinical sampling includes nasal and
      throat washes for virus recovery, blood for clinical chemistry, analysis of B-
      and T-cell response and, more recently, analysis of human genes responding to
      infection. The authors' studies are resulting in new developments of universal
      influenza vaccines that could stimulate and prime CD4 and CD8 cells to shared
      epitopes in all influenza A viruses. Ethnographic study has noted an absence of
      quarantine stress in the volunteers for the first time.

PMID- 23002975
TI  - PATH Influenza Vaccine Project: accelerating the development of new influenza
      vaccines for low-resource countries.
AB  - The 2009 influenza A/H1N1 pandemic demonstrated that a pandemic influenza virus
      has the potential to spread more rapidly in today's highly interconnected world
      than in the past. While pandemic morbidity and mortality are likely to be
      greatest in low-resource countries, manufacturing capacity and access to
      influenza vaccines predominantly exist in countries with greater resources and
      infrastructure. Even with recently expanded manufacturing capacity, the number of
      doses available within a 6-month timeframe would be inadequate to fully immunize
      the global population if the decision to implement a global vaccination program
      were made today. Improved, affordable vaccines are needed to limit the
      consequences of a global influenza outbreak and protect low-resource populations.
      PATH's Influenza Vaccine Project is supporting a range of activities in
      collaboration with private- and public-sector partners to advance the development
      of promising influenza vaccines that can be accessible and affordable for people
      in low-resource countries.

PMID- 23002976
TI  - Influenza vaccines: T-cell responses deserve more attention.
AB  - Currently licensed influenza vaccines rely predominantly on the induction of
      strain-matched hemagglutination inhibition antibody responses. These vaccines
      have a proven record of safety and efficacy in preventing influenza-induced
      illness and complications. However, they do not confer protection to all
      vaccinated individuals, and the protection they afford is short-lived,
      particularly in older adults. Hemagglutination inhibition titers induced by these
      vaccines are considered correlates of protection, but recent data demonstrate
      that this is not always the case. It is clear that better insight is needed into
      the immune responses that correlate with protection against human influenza.
      Influenza vaccines that can induce cross-reactive cellular immune responses
      (CD4(+) and/or CD8(+) T-cell responses) might correct some of the shortcomings of
      currently used influenza vaccines. In the future, the use of infection-permissive
      and disease-modifying vaccines that allow for the induction of cross-reactive T
      cell responses may become a valuable complement to the administration of
      trivalent inactivated influenza vaccines.

PMID- 23002977
TI  - Pediatric influenza vaccination: understanding the T-cell response.
AB  - Influenza A virus-specific T cells are highly cross-reactive and contribute to
      heterosubtypic immunity, which may afford protection against novel pandemic
      strains of influenza virus. However, the magnitude and nature of virus-specific T
      cell responses induced by natural infections and/or vaccination in young children
      is poorly understood. Host factors, such as the development of the immune system
      during childhood and environmental factors such as exposure rates to influenza
      viruses and interference by vaccination contribute to shaping the magnitude and
      specificity of the T-cell response. Here, the authors review several of these
      factors, including the differences between T-cell responses of young children and
      adults, the age-dependent frequency of virus-specific T cells and the impact of
      annual childhood influenza vaccination. In addition, the authors summarize all
      currently available studies in which influenza vaccine-induced T-cell responses
      were evaluated. The authors discuss these findings in the light of developing
      vaccines and vaccination strategies aiming at the induction of protective
      immunity to seasonal and pandemic influenza viruses of antigenically distinct
      subtypes.

PMID- 23002978
TI  - Assessing the safety of influenza vaccination in specific populations: children
      and the elderly.
AB  - Comprehensive monitoring of the safety of influenza vaccines remains a public
      health priority, particularly as immunization coverage increases across different
      age groups at the global level. In this review, the authors provide state-of-the
      art knowledge on the safety of influenza immunization among children and the
      elderly. The authors review the safety information in each group separately for
      inactivated and live attenuated influenza vaccines. Adverse events of special
      concern including febrile seizure, narcolepsy, asthma and Guillain-Barre syndrome
      are covered under specific considerations. The authors discuss the current status
      of the field, particularly the use of new technologies for influenza vaccines and
      their potential safety profile.

PMID- 23002981
TI  - Vaccination against influenza: role and limitations in pandemic intervention
      plans.
AB  - Influenza pandemics occur periodically and the subtype of the next pandemic
      strain cannot be predicted. Vaccination remains a critical intervention during
      pandemics, but current production technology requires several months to develop
      sufficient vaccine to meet anticipated worldwide need. Candidate prepandemic
      vaccines for use in population priming or rapid deployment during an epidemic are
      in development but are subtype specific and logistical obstacles to timely
      distribution exist. Intensive research is underway to identify a universal
      vaccine, providing protection against all known influenza strains based on shared
      epitopes. Vaccine access is expected to be limited during early response to a
      pandemic, necessitating ethical vaccine distribution plans for within-country and
      global allocation. Mass vaccination plans must be in place prior to an event to
      ensure appropriate infrastructures are in place. Carefully crafted education
      campaigns regarding pandemic vaccine safety and efficacy should aid in maximizing
      pandemic vaccine uptake during a future event.

PMID- 23002979
TI  - Understanding the immune response to seasonal influenza vaccination in older
      adults: a systems biology approach.
AB  - Annual vaccination against seasonal influenza is recommended to decrease disease
      related mortality and morbidity. However, one population that responds
      suboptimally to influenza vaccine is adults over the age of 65 years. The natural
      aging process is associated with a complex deterioration of multiple components
      of the host immune system. Research into this phenomenon, known as
      immunosenescence, has shown that aging alters both the innate and adaptive
      branches of the immune system. The intricate mechanisms involved in immune
      response to influenza vaccine, and how these responses are altered with age, have
      led us to adopt a more encompassing systems biology approach to understand
      exactly why the response to vaccination diminishes with age. Here, the authors
      review what changes occur with immunosenescence, and some immunogenetic factors
      that influence response, and outline the systems biology approach to understand
      the immune response to seasonal influenza vaccination in older adults.

PMID- 23002983
TI  - Killing the bill online? Pathways to young people's protest engagement via social
      media.
AB  - In spring 2011, thousands of Wisconsin residents protested a controversial bill
      spearheaded by Governor Scott Walker. Protest engagement via social media was
      popular, especially among young people. The current study examines the
      relationship between young people's informational and expressive uses of four
      social media-Facebook, YouTube, Twitter, and Blogs-and their offline protest
      engagement. Survey results reveal that although college students used these
      social media to obtain information about the budget repair bill protests, only
      expressive uses related to offline protest engagement. We move research forward
      by examining the implications of multiple uses of political social media
      surrounding a compelling case study.

PMID- 23002984
TI  - The German version of the internet addiction test: a validation study.
AB  - Reports about excessive Internet use, possibly amounting to an addiction, have
      increased. Progress with research and treatment of this phenomenon requires valid
      standardized assessment instruments. A frequently used questionnaire is the
      Internet Addiction Test (IAT) by Kimberly Young. The 20-item questionnaire is
      well established in a number of languages, but a German validation was lacking so
      far. An online (ON) sample (n=1,041, age 24.2+/-7.2 years, 46.7 percent men)
      completed an Internet version of the IAT and a student sample (offline [OF]
      sample, n=841, age: 23.5+/-3.0 years, 46.8 percent men) filled in a paper/pencil
      version. The participants also answered questions regarding their Internet use
      habits. A further sample of 108 students (21.5+/-2.0 years, 25.7 percent men)
      completed the questionnaire twice to determine the 14-day retest reliability. The
      internal consistencies were alpha=0.91 (ON) and alpha=0.89 (OF). Item-whole
      correlations ranged from r=0.23 to r=0.65 (ON) and from r=0.30 to r=0.64 (OF).
      Two-week retest reliability was r(tt)=0.83. Factor analyses with Varimax rotation
      yielded the same two factors in both samples, which explained 46.7 percent (ON)
      and 42.0 percent (OF) of the variance. The IAT score correlated with the time
      spent in the Internet in a typical week (ON: r=0.44; OF: r=0.38). The German
      version of the IAT was shown to have good psychometric properties and a stable
      two-factorial structure. Correlations with online time were in line with those
      reported for the IAT in other languages.

PMID- 23002980
TI  - Virus-like particles as universal influenza vaccines.
AB  - Current influenza vaccines are primarily targeted to induce immunity to the
      influenza virus strain-specific hemagglutinin antigen and are not effective in
      controlling outbreaks of new pandemic viruses. An approach for developing
      universal vaccines is to present highly conserved antigenic epitopes in an
      immunogenic conformation such as virus-like particles (VLPs) together with an
      adjuvant to enhance the vaccine immunogenicity. In this review, the authors focus
      on conserved antigenic targets and molecular adjuvants that were presented in
      VLPs. Conserved antigenic targets that include the hemagglutinin stalk domain,
      the external domain of influenza M2 and neuraminidase are discussed in addition
      to molecular adjuvants that are engineered to be incorporated into VLPs in a
      membrane-anchored form.

PMID- 23002985
TI  - Are digital games perceived as fun or danger? Supporting and suppressing
      different game-related concepts.
AB  - Violent digital game play has repeatedly been discussed to be strongly related to
      aggression and emotional instability. Thus, digital game players have to defend
      against these prejudices through emphasizing positive game-related concepts such
      as achievement, social interaction, and immersion. We experimentally investigated
      which positive- and negative-concept players and nonplayers activate when being
      primed with digital games. Participants were either exposed to violent or
      nonviolent game content and were required to work on a lexical decision task.
      Results showed that response latencies for the concept aggression and emotional
      instability were faster than for neutral concepts (not associated with digital
      games), but slower than for the positive concepts sociality and competition. Both
      players and nonplayers felt the need to defend against prejudices and emphasized
      positive concepts. Neither their own gaming experience nor the game content
      influenced the results. Being a part of the net generation is sufficient to
      suppress negative game-related concepts and to support positive game-related
      concepts to protect digital games as common leisure activity among peers.

PMID- 23002986
TI  - The relationship between Internet addiction and depression among migrant children
      and left-behind children in China.
AB  - With greater Internet availability, the pathological use of the Internet has
      become an emerging mental health issue among adolescents in China. The objective
      of this study was to examine the associations between Internet addiction and
      depression in migrant children (MC) and left-behind children (LBC). The present
      study was conducted using a cross-sectional design with 3,254 participants (8-17
      years old), which included 1143 LBC, 574 MC, and 1287 nonleft-behind rural
      children (RC) from 12 schools. Young's 8-item Internet Addiction Scale was used
      to assess Internet dependency. The Children's Depression Inventory-Short Form was
      used to measure child depression. The results showed that the prevalence of
      depression was 10.9 percent among RC, 19.7 percent among MC, and 14.3 percent
      among LBC. The prevalence of Internet addiction was 3.7 percent among RC, and was
      6.4 percent among MC and 3.2 percent among LBC. Depression was effected by the
      interaction between types of children and Internet addiction. LBC with Internet
      addiction (odds ratio [OR], 2.780; 95 percent confidence interval [CI], 1.237
      6.248), MC with Internet addiction (OR, 2.922; 95 percent CI, 1.116-7.652), and
      MC with no Internet addiction (OR, 2.735; 95 percent CI, 1.974-3.789) had higher
      risks of depression than that for RC with no-Internet addiction. The results
      indicated that Internet addiction might be associated with an increased risk of
      depression in LBC, and migration was an important risk factor for child
      depression.

PMID- 23002987
TI  - Developing a web site for human immunodeficiency virus prevention in a middle
      income country: a pilot study from Thailand.
AB  - The Internet has often been used to reach men who have sex with men (MSMs) in
      developed countries. However, its use has not been as widespread in middle income
      countries because of a perceived lack of access to the web by residents of these
      countries. However, over half of the Internet users in the world now live in
      middle income countries. This article describes the development of web-based
      human immunodeficiency virus (HIV) prevention program that can serve as a model
      for middle income countries. Thai nursing faculty worked with MSMs to create and
      evaluate a Web site that provided HIV prevention messages directed toward MSMs.
      The steps for creating the site are described. Forty-one MSMs used the site and
      provided feedback to the site developers. The group was young (median=19 years),
      low income (median income was ~170 US$ per month). The users demonstrated that
      they had access to the Internet and that they could utilize the site. They also
      reported moderate-to-high levels of satisfaction with site design, content, ease
      of use, information obtained, and benefits obtained from using the site. A
      previous article in the Thai language also showed that they reduced risk
      behaviors. They also made many useful suggestions for improving the content of
      the site. In conclusion, the study showed that the combination of nurses and MSMs
      from a middle income country could develop a usable HIV prevention Web site that
      instructed and changed behavior.

PMID- 23002988
TI  - Cyberbullying among primary school students in Turkey: self-reported prevalence
      and associations with home and school life.
AB  - The current study examined the self-reported prevalence and nature of
      cyberbullying and victimization among second, third, and fourth grade students
      (N=372) and explored associated features of home and school life. Of the children
      in the current sample, 27 percent had been victims of cyberbullying, 18 percent
      had been aggressors, and 15 percent had been both cyberbullies and victims. Boys
      were significantly more likely to carry out cyberbullying than girls.
      Cyberbullying exposure (as both a bully and a victim) was significantly
      associated with low levels of self-reported school satisfaction (bullies odds
      ratio [OR]: 2.45; victims OR: 2.10; p<0.05) and achievement (bullies OR: 3.85;
      victims OR: 3.47, p<0.05). Paternal unemployment was also associated with a three
      fold increase in the likelihood of being a cyberbully. Increased awareness and
      regulation is now required within schools and within the home to tackle this
      escalating problem.

PMID- 23002989
TI  - The validity of administrative data to classify patients with spinal column and
      cord injuries.
AB  - International Classification of Diseases (ICD) codes are used to document patient
      morbidity in administrative databases. Although administrative data are used for
      research purposes, the validity of the data to accurately describe clinical
      diagnostic information is uncertain. We compared the clinical diagnoses for
      spinal cord and column injuries from a longitudinal patient registry, the Rick
      Hansen Spinal Cord Injury Registry (RHSCIR), to the ICD-10 spinal injury codes
      from the Discharge Abstract Database (DAD) at one institution. There were 603
      RHSCIR participants with data describing the spinal cord injury, and 341 had data
      on the spinal column injury. The validity of DAD data to describe spinal injuries
      was evaluated using the sensitivity and positive predictive values of specific
      ICD-10 codes; 5.3% of the spinal column injuries and 10.9% of the spinal cord
      injuries documented in RHSCIR were missed in data from the DAD using ICD-10
      codes. The most problematic spinal column ICD-10 code was the dislocation of the
      cervical vertebra (S13.1); only 14.0% of the dislocations of the cervical
      vertebrae in RHSCIR were correctly coded in the DAD. The most problematic spinal
      cord injury ICD-10 code was the incomplete lesion of the lumbar spinal cord
      (S34.1X); 66.7% of incomplete lesions of the lumbar spinal cord in RHSCIR were
      correctly coded in the DAD. The validity of DAD data to code spinal injuries is
      variable, and cannot be reliably used to classify all types of spinal injuries.
      Patient registries, such as RHSCIR, should be used if accurate detailed
      diagnostic data are required.

PMID- 23002990
TI  - Copper-catalyzed synthesis of trisubstituted isoxazoles via a cascade cyclization
      migration process.
AB  - An atom-economical, catalytic, and regioselective synthesis of 3,4,5
      trisubstituted isoxazoles has been successfully developed. Treatment of O
      arylmethyl alkynyl oxime ethers with 5 mol % of Cu(OTf)(2) in chlorobenzene at
      reflux gave 4-arylmethylisoxazoles in good to excellent yields via the sequential
      intramolecular addition of the oxime moiety to the alkyne with subsequent 1,3
      migration of the arylmethyl group.

PMID- 23002991
TI  - Environmentally friendly lycopene purification from tomato peel waste: enzymatic
      assisted aqueous extraction.
AB  - The antioxidant and anticancer properties of lycopene make it an ideal component
      for daily food supplements. For this reason this study investigated the
      possibility of extracting lycopene from tomato waste peels using a green
      chemistry protocol devoid of organic solvent. Cells are lysed thanks to a
      combination of pH changes and hydrolytic enzyme treatments. The lycopene
      containing chromoplasts are then precipitated by lowering the pH and isolated
      through a centrifugation step. At this stage the lycopene content of the isolated
      chromoplasts shows a 10-fold increase (3-5% w/w, dry basis) with respect to
      untreated tomato peels. A further improvement in lycopene concentration is
      obtained by a second enzymatic treatment using a protease cocktail. This
      catalytic step eliminates unwanted proteins, bound to the chromoplasts, but not
      essential for their stability. The final product shows a lycopene content around
      8-10% (w/w, dry basis), which represents a 30-fold increase with respect to the
      lycopene concentration of the untreated peels.

PMID- 23002994
TI  - Methane to methanol conversion induced by thorium oxide through the CH3Th(O)H
      intermediate in solid argon.
AB  - Reactions of ThO molecules and CH(4) have been investigated in solid argon near 4
      K. The CH(3)Th(O)H molecule is produced when the sample is exposed to UV
      irradiation. Identification of this new intermediate is substantiated by
      observation of the Th?O and Th-H stretching vibrational modes with isotopic
      substitution via matrix infrared spectroscopy, and the assignments are supported
      by electronic structure frequency calculations. Methanol absorptions increase
      together with formation of the CH(3)Th(O)H molecule, suggesting a methane to
      methanol conversion induced by thorium oxide proceeding through the CH(3)Th(O)H
      intermediate. The formation of CH(3)Th(O)H from ThO + CH(4) is exothermic
      (DeltaH(rxn) = -11 kcal/mol) with an energy barrier of 30 kcal/mol at the
      CCSD(T)//B3LYP level. Decomposition of this intermediate to form methanol
      involves spin crossing, and the overall reaction from the intermediate is
      endothermic by 127 kcal/mol. There is no activation energy for the reaction of
      thorium atoms with methanol to give CH(3)Th(O)H, as observed in separate
      experiments with Th and CH(3)OH.

PMID- 23002995
TI  - Identifying risk and preventing progression to Type 2 diabetes in vulnerable and
      disadvantaged adults: a pragmatic review.
AB  - AIM: To identify effective approaches to recognize diabetes risk and prevent
      progression to Type 2 diabetes in vulnerable groups, whose diabetes risk may be
      difficult to identify or manage. METHODS: UK-based interventions that assess
      diabetes risk and/or target known risk factors were identified through four main
      sources: submissions to two calls for evidence by the National Institute for
      Health and Clinical Excellence; local practice examples collected via a targeted
      email questionnaire; selected electronic databases; and a focused search of
      relevant websites. No restriction was placed on the study type or evaluation
      methods used. Key themes and sub-themes on outcomes, as well as facilitators and
      barriers to successful delivery, are reported. RESULTS: Twenty-four interventions
      met all inclusion criteria: 15 included a risk identification element and 14
      included preventative activities. A range of risk identification tools were used
      to improve diagnosis of unmet diabetes-related health needs and raise awareness
      of diabetes risk factors. All preventative interventions focused on lifestyle
      change. No interventions monitored blood glucose as an outcome and only one
      reported improvements in baseline risk scores. Facilitators included tailored and
      flexible programme design, outreach delivery in familiar locations and effective
      inter-agency working. Barriers included literacy and language difficulties,
      transient participant populations, low prioritization of diabetes prevention and
      cost. CONCLUSIONS: It is possible to engage successfully with high-risk adults in
      vulnerable groups to achieve positive health outcomes relevant to the prevention
      of diabetes. However, more robust evidence on longer-term outcomes is required to
      ensure that programmes are targeted and delivered appropriately.

PMID- 23002992
TI  - Comparative study of enzyme activity and heme reactivity in Drosophila
      melanogaster and Homo sapiens cystathionine beta-synthases.
AB  - Cystathionine beta-synthase (CBS) is the first and rate-limiting enzyme in the
      transsulfuration pathway, which is critical for the synthesis of cysteine from
      methionine in eukaryotes. CBS uses coenzyme pyridoxal 5'-phosphate (PLP) for
      catalysis, and S-adenosylmethionine regulates the activity of human CBS, but not
      yeast CBS. Human and fruit fly CBS contain heme; however, the role for heme is
      not clear. This paper reports biochemical and spectroscopic characterization of
      CBS from fruit fly Drosophila melanogaster (DmCBS) and the CO/NO gas binding
      reactions of DmCBS and human CBS. Like CBS enzymes from lower organisms (e.g.,
      yeast), DmCBS is intrinsically highly active and is not regulated by AdoMet. The
      DmCBS heme coordination environment, the reactivity, and the accompanying effects
      on enzyme activity are similar to those of human CBS. The DmCBS heme bears
      histidine and cysteine axial ligands, and the enzyme becomes inactive when the
      cysteine ligand is replaced. The Fe(II) heme in DmCBS is less stable than that in
      human CBS, undergoing more facile reoxidation and ligand exchange. In both CBS
      proteins, the overall stability of the protein is correlated with the heme
      oxidation state. Human and DmCBS Fe(II) hemes react relatively slowly with CO and
      NO, and the rate of the CO binding reaction is faster at low pH than at high pH.
      Together, the results suggest that heme incorporation and AdoMet regulation in
      CBS are not correlated, possibly providing two independent means for regulating
      the enzyme.

PMID- 23002997
TI  - Correlational selection on pro- and anti-inflammatory effectors.
AB  - Parasites impose a permanent threat for hosts. As a consequence, immune defenses
      are important for host fitness. However, the immune response can also produce
      self-damage and impair host fitness if not properly regulated. Effectors that up-
      and downregulate the immune response should, therefore, evolve in concert, and be
      under the action of correlational selection. To address this issue, we assessed
      the shape of the selection operating on pro- and anti-inflammatory effectors
      following an inflammatory challenge in laboratory mice.We found that selection
      acts on the combination of these two traits as individuals that produced large
      amount of pro-inflammatory cytokines could achieve relatively high fitness
      (survival) only if also producing a large amount of anti-inflammatory effectors.
      To our knowledge, this is the first study providing evidence for correlational
      selection on immunity.

PMID- 23002996
TI  - Antibody levels correlate with detection of Trypanosoma cruzi DNA by sensitive
      polymerase chain reaction assays in seropositive blood donors and possible
      resolution of infection over time.
AB  - BACKGROUND: The clinical significance of anti-Trypanosoma cruzi low-level
      reactive samples is incompletely understood. Polymerase chain reaction (PCR)
      positive rates and antibody levels among seropositive blood donors in three
      countries are described. STUDY DESIGN AND METHODS: Follow-up samples were
      collected from T. cruzi-seropositive donors from 2008 through 2010 in the United
      States (n = 195) and Honduras (n = 58). Also 143 samples from Brazil in 1996 to
      2002, originally positive by three serologic assays, were available and paired
      with contemporary follow-up samples from these donors. All samples were retested
      with Ortho enzyme-linked immunosorbent assay (ELISA). PCR assays were performed
      on coded sample panels by two laboratories (Blood Systems Research Institute
      [BSRI] and American Red Cross Holland Laboratory [ARC]) that amplified
      kinetoplast minicircle DNA sequences of T. cruzi. RESULTS: PCR testing at BSRI
      yielded slightly higher overall sensitivity and specificity (33 and 98%) compared
      with those at the ARC (28 and 94%). Among seropositive donors, PCR-positive rates
      varied by country (p < 0.0001) for the BSRI laboratory: Brazil (57%), Honduras
      (32%), and the United States (14%). ELISA signal-to-cutoff ratios (S/CO) were
      significantly higher for PCR-positive compared to PCR-negative donors (p < 0.05
      for all comparisons). Additionally, PCR-negative Brazilian donors exhibited
      greater frequencies of antibody decline over time versus PCR-positive donors (p =
      0.003). CONCLUSION: For all three countries, persistent DNA positivity correlated
      with higher ELISA S/CO values, suggesting that high-level seroreactivity reflects
      chronic parasitemia. Significant S/CO declines in 10% of the PCR-negative
      Brazilian donors may indicate seroreversion after parasite clearance in the
      absence of treatment.

PMID- 23002998
TI  - Editorial comment from Dr Vazquez-Alonso and Dr Puche-Sanz to impact of
      hyponatremia on survival of patients with metastatic renal cell carcinoma treated
      with molecular targeted therapy.

PMID- 23002999
TI  - Intrauterine diagnosis and treatment of fetal goitrous hypothyroidism.
AB  - We present two cases of fetal hypothyroidism with goiter which were successfully
      diagnosed and treated in utero. In both cases, ultrasonographic examination
      demonstrated a bilobed solid anterior neck mass with increased vascularity
      compatible with enlarged thyroid gland. Fetal blood sampling revealed
      hypothyroidism. Intra-amniotic injection of L-thyroxin caused a reduction in
      thyroid gland size and enabled vaginal delivery without complication. In the
      first case, maternal thyroid hormone levels and autoantibodies were normal and
      the neonate had hypothyroidism suggesting the diagnosis of dyshormonogenesis. In
      the second case, the fetus had transient hypothyroidism, which resolved
      spontaneously after delivery. Maternal thyroid function tests and autoantibodies
      were normal and both the mother and neonate had normal urinary iodine, excluding
      the diagnosis of iodine deficiency or excess. Thus, we believe that
      transplacental transfer of undetermined factors might be a cause of transient
      congenital hypothyroidism. Also, we reviewed the literature and described
      controversial issues regarding the management of fetal goiter.

PMID- 23003000
TI  - Effect of exposure to evidence-based pharmacotherapy on outcomes after acute
      myocardial infarction in older adults.
AB  - OBJECTIVES: To assess the effect of exposure to evidence-based medication after
      hospital discharge for Medicare beneficiaries with acute myocardial infarction
      (AMI). DESIGN: A discrete-time hazard model was used to estimate time to outcome
      associated with exposure to four drug classes (angiotensin-converting enzyme
      inhibitors (ACEIs)/angiotensin-II receptor blockers (ARBs), beta-blockers (BBs),
      statins, and clopidogrel) used for post-AMI secondary prevention of
      cardiovascular events and mortality. SETTING: Medicare administrative data for a
      5% random sample of beneficiaries. PARTICIPANTS: Medicare beneficiaries (N =
      9,538) hospitalized for an AMI between April 1, 2006, and December 31, 2007, who
      survived for at least 30 days after discharge. The cohort was followed until
      death or December 31, 2008. MEASUREMENTS: Time-varying exposure was measured as
      proportion of days covered (PDC) for each quarter during the follow-up period.
      PDC was classified into five categories (0-0.2, 0.2-0.4, 0.4-0.6, 0.6-0.8, 0.8
      1.0). Outcomes were mortality and a composite outcome of death or post-AMI
      hospitalization. RESULTS: Over a median follow-up of 18 months, mean PDC rates
      ranged from 0.37 (clopidogrel) to 0.50 (statins). When comparing the highest
      versus lowest categories of exposure, the hazard of the composite outcome was
      significantly lower for all drug classes except BBs (statins, adjusted hazard
      ratio (aHR) = 0.71, ACEIs/ARBs, aHR = 0.81, clopidogrel, aHR = 0.85, BBs, aHR =
      0.93). All four drug classes were significantly associated with reductions in
      mortality; the magnitude of effect for the mortality outcome was largest for
      statins and smallest for BBs. Age modified the effect of statins on mortality.
      CONCLUSION: Use of evidence-based medications for secondary prevention after AMI
      is suboptimal in the Medicare population, and low exposure rates are associated
      with significantly higher risk for subsequent hospitalization and death.

PMID- 23003002
TI  - Actigraphic analysis of the sleep-wake cycle and physical activity level in
      patients with stroke: implications for clinical practice.
AB  - Several structures of the central nervous system are essential in the sleep-wake
      regulation process. This study aimed to identify which actigraphic parameters of
      the sleep-wake cycle (SWC) are compromised after stroke and determine whether low
      level physical activity can influence the expression of sleep-cycle temporal
      variation, in order to discuss the implications for the clinical practice of
      patient rehabilitation. The study assessed 22 patients (55 +/- 12 years) and 24
      healthy individuals (57 +/- 11 years), of both sexes. The instruments used were
      the International Physical Activity Questionnaire (IPAQ) and Actigraphy. Data
      were analyzed by the student t, Mann-Whitney, and Spearman's correlation tests.
      Patients' activity level was about 28% lower than that of healthy subjects.
      Furthermore, we recorded around 10% more activity in the sleep phase compared to
      the controls, indicating that patients suffer from fragmented sleep (p < .001).
      According to IPAQ classification, we observed that healthy individuals were
      classified more predominantly as active (66.7%) and patients as irregularly
      active B (72.8%). A significant correlation was found between IPAQ and total
      activity (R= -.25; p= .007) and sleep latency (R= .27; p= .0006). In conclusion,
      the results obtained show a decrease in activity intensity in the SWC and
      significant sleep alterations related to greater duration, latency, and
      fragmentation. It is suggested that, in addition to motor impairments, sleep
      disorder complaints should be given priority during clinical diagnosis of
      patients with stroke.

PMID- 23003001
TI  - Paracrine proangiopoietic effects of human umbilical cord blood-derived purified
      CD133+ cells--implications for stem cell therapies in regenerative medicine.
AB  - CD133+ cells purified from hematopoietic tissues are enriched mostly for
      hematopoietic stem/progenitor cells, but also contain some endothelial progenitor
      cells and very small embryonic-like stem cells. CD133+ cells, which are akin to
      CD34+ cells, are a potential source of stem cells in regenerative medicine.
      However, the lack of convincing donor-derived chimerism in the damaged organs of
      patients treated with these cells suggests that the improvement in function
      involves mechanisms other than a direct contribution to the damaged tissues. We
      hypothesized that CD133+ cells secrete several paracrine factors that play a
      major role in the positive effects observed after treatment and tested
      supernatants derived from these cells for the presence of such factors. We
      observed that CD133+ cells and CD133+ cell-derived microvesicles (MVs) express
      mRNAs for several antiapoptotic and proangiopoietic factors, including kit
      ligand, insulin growth factor-1, vascular endothelial growth factor, basic
      fibroblast growth factor, and interleukin-8. These factors were also detected in
      a CD133+ cell-derived conditioned medium (CM). More important, the CD133+ cell
      derived CM and MVs chemoattracted endothelial cells and display proangiopoietic
      activity both in vitro and in vivo assays. This observation should be taken into
      consideration when evaluating clinical outcomes from purified CD133+ cell
      therapies in regenerative medicine.

PMID- 23003003
TI  - Corrected confidence bands for functional data using principal components.
AB  - Functional principal components (FPC) analysis is widely used to decompose and
      express functional observations. Curve estimates implicitly condition on basis
      functions and other quantities derived from FPC decompositions; however these
      objects are unknown in practice. In this article, we propose a method for
      obtaining correct curve estimates by accounting for uncertainty in FPC
      decompositions. Additionally, pointwise and simultaneous confidence intervals
      that account for both model- and decomposition-based variability are constructed.
      Standard mixed model representations of functional expansions are used to
      construct curve estimates and variances conditional on a specific decomposition.
      Iterated expectation and variance formulas combine model-based conditional
      estimates across the distribution of decompositions. A bootstrap procedure is
      implemented to understand the uncertainty in principal component decomposition
      quantities. Our method compares favorably to competing approaches in simulation
      studies that include both densely and sparsely observed functions. We apply our
      method to sparse observations of CD4 cell counts and to dense white-matter tract
      profiles. Code for the analyses and simulations is publicly available, and our
      method is implemented in the R package refund on CRAN.

PMID- 23003004
TI  - Long-term outcome of breast cancer patients with one to two nodes involved -
      application of nodal ratio.
AB  - Nodal ratio (NR) is defined as the number of involved nodes to the number of
      nodes examined. There is limited information on the application of NR on
      population data. Previous reports in breast cancer generally analyzed one to
      three positive axillary nodes as a single group. This study investigates whether
      one to three positive axillary nodes is a homogeneous group in prognosis by
      comparing one to two positive nodes to three positive nodes. The population-based
      registry of a Canadian province from 1981 through 1995 was searched. As the
      reliability of nodal assessment depends on the number of nodes sampled, we also
      studied the subgroup of patients with greater than or equal to eight nodes
      dissected. Of a total of 5,996 breast cancer patients, 1187 had one to three
      positive axillary nodes. The 263 patients with three positive nodes compared to
      the 924 patients with one to two nodes fared worse with a significantly reduced
      cause-specific survival (CSS) and overall survival (OS). Patients with one to two
      positive nodes had similar CSS (p=0.31) and OS (p=0.63). Among those with greater
      than or equal to eight nodes dissected, there were 677 patients with one to two
      positive nodes. CSS and OS were not significantly different between one versus
      two positive nodes (p=0.16 and 0.34, respectively), but with NR, the
      corresponding p values were 0.0068 and 0.08, respectively. The cutoff value of NR
      0.15 was found to be most useful and confirmed by the validation dataset. NR is
      able to segregate patients better than the absolute number of positive nodes used
      in the current staging system. NR should be incorporated into the staging system.

PMID- 23003005
TI  - Development of an immunosensor assay for detection of haptoglobin in mastitic
      milk.
AB  - BACKGROUND: Detection of subclinical mastitis in dairy cows is important, as it
      represents a major economic challenge for the dairy industry worldwide owing to
      propagation of mastitis-causing pathogens and to long-term reduction in milk
      yield and quality. Haptoglobin (Hp) is one of the most sensitive acute phase
      proteins in milk during udder inflammation and as an indicator of mastitis.
      OBJECTIVES: The aim of this study was to develop a rapid and sensitive
      immunosensor assay for measuring Hp concentration in mastitic milk. METHODS: The
      immunosensor was constructed by immobilizing anti-bovine Hp antibody on a gold
      electrode through gold nanoparticles fabricated on self-assembled L-cysteine
      layers. The immunosensor assay was used to measure Hp concentration in 20 milk
      samples positive for bacteria with a somatic cell count > 5 * 10(5) cells/mL from
      cows without clinical signs of mastitis. Results were compared with those
      obtained using a commercial ELISA kit. RESULTS: Reproducibility of Hp measurement
      and stability after storage for 20 days were good for the immunosensor assay.
      Measurement of Hp was linear over a range of 15-100 mg/L, with a limit of
      detection of 0.63 mg/L. Agreement between results obtained with the immunosensor
      and ELISA methods was satisfactory as analyzed using the Wilcoxon signed-rank
      test (Z = -1.739, P = .073). CONCLUSION: An immunosensor assay for measuring Hp
      in milk provided rapid results and was easy to perform, facilitating its
      potential use in the field for the diagnosis of subclinical mastitis once a
      cutoff value for Hp concentration is established.

PMID- 23003007
TI  - CDX2 highlights mucinous epithelium in hepatoblastoma with teratoid components.
AB  - Originally only considered as a maker for intestinal differentiation, CDX2 was
      later found to be expressing in other tumors outside of gastrointestinal (GI)
      tract. We report an interesting phenomenon that CDX2 also highlighted the
      teratoid component in hepatoblastoma-its mucinous epithelium. It is speculated
      that CDX2 can be a good marker for mucinous differentiation with morphological
      intestinal characteristics in general.

PMID- 23003006
TI  - Biopharmaceutical characterization of decursin and their derivatives for drug
      discovery.
AB  - Angelica gigas Nakai and its components are known to have neuroprotective,
      antiplatelet, and anticancer activities. The present study evaluated the in vitro
      and in vivo biopharmaceutical characterization of Angelica gigas component
      substances, including decursin (the main substance), decursinol angelate
      (decursin isomer), JH714 (ether form of decursin) and epoxide decursin (epoxide
      form of decursin). Decursin, decursinol angelate and JH714 exhibited acceptable
      metabolic stability (>50%) in liver microsomes from human and higher bound
      fraction (>90%) in human plasma operating ultrafiltration. Decursin and
      decursinol angelate in CYP1A2 and CYP2C19 indicated less than 50% CYP activity,
      suggesting inhibition of the CYP isoforms using Vivid(r) CYP screening kit. JH714
      only showed an apparent permeability coefficient of <10 * 10-6 cm/s in MDCK
      cells, suggesting that it is poorly absorbed. Blood brain barrier permeability
      was examined after oral administration to male Sprague-Dawley (SD) rats, and
      pharmacokinetic studies were performed after oral and intravenous administration
      of 10 mg/kg compounds. Decursin, decursinol angelate and JH714 showed ratios of
      compound concentration in brain with respect to plasma (Cbrain/Cplasma) of >1.5,
      suggesting good brain/plasma ratio at 0.5, 1, 3, and 5 h. In contrast,
      Cbrain/Cplasma was <0.5 for epoxide decursin. For all test compounds, >1.5% of
      the dose remained in GI tract after 8 h, and the excretion rate in urine was
      <0.5% which suggests that gastro intestinal tract may be major site of
      disposition following oral administration. Finally, these results may be useful
      for the design of dosage regimens of decursin and its derivatives.

PMID- 23003008
TI  - Imidazoline derivatives: a patent review (2006--present).
AB  - INTRODUCTION: Recent decades have witnessed the growing interest in the
      development of imidazoline derivatives in drug discovery due to increased
      knowledge in pathogenesis of many diseases. Imidazoline structure has been one of
      the most sought-after scaffolds employed in developing various agents with
      different kinds of pharmacological activities. During 2006 - 2012, imidazoline
      structures have been found in numerous patented compounds for the treatment of
      neurodegenerative diseases and cancer. AREAS COVERED: This paper provides a
      general review of patented imidazoline derivatives from 2006 to 2012. Information
      from articles published in international peer-reviewed journals has also been
      included to give a more exhaustive overview. EXPERT OPINION: With the uncovering
      of the molecular mechanisms related to neurodegenerative diseases and cancer, the
      use of classical and novel imidazoline structures has been more frequently noted
      in recent (2006 - 2012) patented agents for the treatment of neurodegenerative
      diseases and cancer instead of agents for the treatment of cardiovascular disease
      noticed earlier.

PMID- 23003009
TI  - Separation of bioactive peptides by membrane processes: technologies and devices.
AB  - Although many patents reported bioactive peptides with numerous demonstrated
      bioactivities and potential applications, there exist some limitations to the
      production of large quantities to satisfy the growing market demands. Indeed,
      considering that most functional peptides are present in complex matrices
      containing a large number of hydrolyzed protein fractions, their separation and
      purification are required. Some advances have been made in the use of
      conventional pressure-driven processes for the continuous production and
      separation of peptides, however, most of these patented technologies are not
      scalable and demonstrate a low selectivity when separating similar sized
      biomolecules. To improve the separation efficiency, the use of an external
      electric field during pressure-driven filtration was proposed and patented.
      However, whatever the claims, the pressure gradient brings about the accumulation
      of peptides at the nearby membrane surface and affects the membrane transport
      selectivity. To overcome these drawbacks, a recent patent proposed the
      simultaneous fractionation of acidic and basic peptides, using a conventional
      electrodialysis cell, in which some ion exchange membranes are replaced by
      ultrafiltration ones. The perspectives in the field of peptide separation will be
      the development of new membrane materials and new equipments such as microfluidic
      devices to improve selectivity and yield of production. 

PMID- 23003010
TI  - On epistasis: a methodological review for detecting gene-gene interactions
      underlying various types of phenotypic traits.
AB  - Genome-wide association study (GWAS) has become a commonly adopted approach for
      revealing the genetic architecture of complex diseases, with respect to
      uncovering the unknown genetic variants involved in the disease, their variations
      in the population and the magnitude of their effects. Though a substantial number
      of disease-susceptibility variants have been identified, the genetic architecture
      of complex diseases has remained elusive. It is unclear how many genetic variants
      in the human genome are associated with diseases, and how the genetic variants
      interact with one another to cause diseases. This challenge is partly due to the
      pervasive gene-gene interactions that underlie complex human diseases. Whereas a
      number of statistical methods have been developed for detecting gene-gene
      interactions, they are designed for various purposes, such as a particular study
      design, the order of the interactions being examined, and the measurement of
      disease phenotypes. This paper provides a survey of the currently available
      statistical methods and patents from the perspective of their application to
      various types of phenotypic traits. We also discuss the strength of each method
      as well as the biological interpretation of results.

PMID- 23003011
TI  - Higher order Pancharatnam-Berry phase and the angular momentum of light.
AB  - The first experimental demonstration of a new Pancharatnam-Berry phase for light
      beams with spatially inhomogeneous, or vector, states of polarization referred to
      as the higher-order Pancharatnam-Berry phase is presented. This new geometric
      phase is proportional to light's total angular momentum, a sum of spin and higher
      dimensional orbital angular momentum, sharply contrasting the well-known
      Pancharatnam-Berry phase associated with the plane wave state of polarization of
      a spatially homogeneous light beam. The higher-order Pancharatnam-Berry phase is
      directly related to the rotational symmetry of a vortex-bearing electromagnetic
      field, associated with the rotational frequency shift of a light beam, and has
      implications in quantum information science as well as other physical systems
      such as electron vortex beams.

PMID- 23003012
TI  - Superactivation of multipartite unlockable bound entanglement.
AB  - The superactivation of multipartite bound entanglement (BE) is a special protocol
      proposed by Shor et al. in 2003, which can distill Einstein-Podolsky-Rosen (EPR)
      entanglement states between two subsystems of two multipartite BE states. Here we
      present the first experimental realization of the superactivation of the BE
      state, in which two copies of the four-partite unlockable BE state in a
      continuous-variable regime are used. Coupling two thermal states with Gaussian
      noises into two submodes of an EPR entangled state on two 50-50 beam splitters
      respectively, the four output optical modes form a four-partite unlocklable BE
      state. Using two EPR entangled states, we experimentally produce two BE states
      first. Then through a superactivation operation involving measurements and
      feedback on the two BE states, an EPR entangled state is distilled out between
      two designated parties of the two four-partite BE states. The experiment
      demonstrates the superadditivity of quantum entanglement as the individual BE
      state cannot be distilled, only two BE states together can be distilled.

PMID- 23003013
TI  - Quantum simulation of interacting fermion lattice models in trapped ions.
AB  - We propose a method of simulating efficiently many-body interacting fermion
      lattice models in trapped ions, including highly nonlinear interactions in
      arbitrary spatial dimensions and for arbitrarily distant couplings. We map
      products of fermionic operators onto nonlocal spin operators and decompose the
      resulting dynamics in efficient steps with Trotter methods, yielding an overall
      protocol that employs only polynomial resources. The proposed scheme can be
      relevant in a variety of fields such as condensed-matter or high-energy physics,
      where quantum simulations may solve problems intractable for classical computers.

PMID- 23003014
TI  - Quantum storage of heralded polarization qubits in birefringent and
      anisotropically absorbing materials.
AB  - Storage of quantum information encoded into heralded single photons is an
      essential constituent of long-distance quantum communication based on quantum
      repeaters and of optical quantum information processing. The storage of photonic
      polarization qubits is, however, difficult because many materials are
      birefringent and have polarization-dependent absorption. Here we present a simple
      scheme that eliminates these polarization effects, and we demonstrate it by
      storing heralded polarization qubits into a solid-state quantum memory. The
      quantum memory is implemented with a biaxial yttrium orthosilicate (Y2SiO5)
      crystal doped with rare-earth ions. Heralded single photons generated from a
      filtered spontaneous parametric down-conversion source are stored, and quantum
      state tomography of the retrieved polarization state reveals an average fidelity
      of 97.5+/-0.4%, which is significantly higher than what is achievable with a
      measure-and-prepare strategy.

PMID- 23003015
TI  - Quantum storage of a photonic polarization qubit in a solid.
AB  - We report on the quantum storage and retrieval of photonic polarization quantum
      bits onto and out of a solid state storage device. The qubits are implemented
      with weak coherent states at the single photon level, and are stored for a
      predetermined time of 500 ns in a praseodymium doped crystal with a storage and
      retrieval efficiency of 10%, using the atomic frequency comb scheme. We
      characterize the storage by using quantum state tomography, and find that the
      average conditional fidelity of the retrieved qubits exceeds 95% for a mean
      photon number MU=0.4. This is significantly higher than a classical benchmark,
      taking into account the poissonian statistics and finite memory efficiency, which
      proves that our crystal functions as a quantum storage device for polarization
      qubits. These results extend the storage capabilities of solid state quantum
      light matter interfaces to polarization encoding, which is widely used in quantum
      information science.

PMID- 23003016
TI  - Realization of reliable solid-state quantum memory for photonic polarization
      qubit.
AB  - Faithfully storing an unknown quantum light state is essential to advanced
      quantum communication and distributed quantum computation applications. The
      required quantum memory must have high fidelity to improve the performance of a
      quantum network. Here we report the reversible transfer of photonic polarization
      states into collective atomic excitation in a compact solid-state device. The
      quantum memory is based on an atomic frequency comb (AFC) in rare-earth ion-doped
      crystals. We obtain up to 0.999 process fidelity for the storage and retrieval
      process of single-photon-level coherent pulse. This reliable quantum memory is a
      crucial step toward quantum networks based on solid-state devices.

PMID- 23003017
TI  - Strong coupling of spin qubits to a transmission line resonator.
AB  - We propose a mechanism for coupling spin qubits formed in double quantum dots to
      a superconducting transmission line resonator. Coupling the resonator to the gate
      controlling the interdot tunneling creates a spin qubit-resonator interaction
      with a strength of tens of MHz. This mechanism allows operating the system at a
      symmetry point where decoherence due to charge noise is minimized. The
      transmission line can serve as the shuttle, allowing for fast two-qubit
      operations including the generation of qubit-qubit entanglement and the
      implementation of a controlled-phase gate.

PMID- 23003018
TI  - Crooks relation in optical spectra: universality in work distributions for weak
      local quenches.
AB  - We show that work distributions and nonequilibrium work fluctuation theorems can
      be measured in optical spectra for a wide class of quantum systems. We consider
      systems where the absorption or emission of a photon corresponds to the sudden
      switch on or off of a local perturbation. For the particular case of a weak local
      perturbation, the Crooks relation establishes a universal relation in absorption
      as well as in emission spectra. Because of a direct relation between the spectra
      and work distribution functions this is equivalent to universal relations in work
      distributions for weak local quenches. As two concrete examples we treat the x
      ray edge problem and the Kondo exciton.

PMID- 23003019
TI  - Thermodynamic metrics and optimal paths.
AB  - A fundamental problem in modern thermodynamics is how a molecular-scale machine
      performs useful work, while operating away from thermal equilibrium without
      excessive dissipation. To this end, we derive a friction tensor that induces a
      Riemannian manifold on the space of thermodynamic states. Within the linear
      response regime, this metric structure controls the dissipation of finite-time
      transformations, and bestows optimal protocols with many useful properties. We
      discuss the connection to the existing thermodynamic length formalism, and
      demonstrate the utility of this metric by solving for optimal control parameter
      protocols in a simple nonequilibrium model.

PMID- 23003020
TI  - Exact solution for the stationary Kardar-Parisi-Zhang equation.
AB  - We obtain the first exact solution for the stationary one-dimensional Kardar
      Parisi-Zhang equation. A formula for the distribution of the height is given in
      terms of a Fredholm determinant, which is valid for any finite time t. The
      expression is explicit and compact enough so that it can be evaluated
      numerically. Furthermore, by extending the same scheme, we find an exact formula
      for the stationary two-point correlation function.

PMID- 23003021
TI  - Generating matter inhomogeneities in general relativity.
AB  - In this Letter we discuss a natural general relativistic mechanism that causes
      inhomogeneities and hence generates matter perturbations in the early Universe.
      We concentrate on spikes, both incomplete spikes and recurring spikes, that
      naturally occur in the initial oscillatory regime of general cosmological models.
      In particular, we explicitly show that spikes occurring in a class of G2 models
      lead to inhomogeneities that, due to gravitational instability, leave small
      residual imprints on matter in the form of matter perturbations. The residual
      matter overdensities from recurring spikes are not local but form on surfaces. We
      discuss the potential physical consequences of the residual matter imprints and
      their possible effect on the subsequent formation of large-scale structure.

PMID- 23003022
TI  - Self-consistent orbital evolution of a particle around a Schwarzschild black
      hole.
AB  - The motion of a charged particle is influenced by the self-force arising from the
      particle's interaction with its own field. In a curved spacetime, this self-force
      depends on the entire past history of the particle and is difficult to evaluate.
      As a result, all existing self-force evaluations in curved spacetime are for
      particles moving along a fixed trajectory. Here, for the first time, we overcome
      this long-standing limitation and present fully self-consistent orbits and
      waveforms of a scalar charged particle around a Schwarzschild black hole.

PMID- 23003023
TI  - Limits on self-interacting dark matter from neutron stars.
AB  - We impose new severe constraints on the self-interactions of fermionic asymmetric
      dark matter based on observations of nearby old neutron stars. Weakly interacting
      massive particle (WIMP) self-interactions mediated by Yukawa-type interactions
      can lower significantly the number of WIMPs necessary for gravitational collapse
      of the WIMP population accumulated in a neutron star. Even nearby neutron stars
      located at regions of low dark matter density can accrete a sufficient number of
      WIMPs that can potentially collapse, form a mini black hole, and destroy the host
      star. Based on this, we derive constraints on the WIMP self-interactions which in
      some cases are by several orders of magnitude stricter than the ones from the
      bullet cluster.

PMID- 23003024
TI  - Standard model false vacuum inflation: correlating the tensor-to-scalar ratio to
      the top quark and Higgs boson masses.
AB  - For a narrow band of values of the top quark and Higgs boson masses, the standard
      model Higgs potential develops a false minimum at energies of about 10(16)  GeV,
      where primordial inflation could have started in a cold metastable state. A
      graceful exit to a radiation-dominated era is provided, e.g., by scalar-tensor
      gravity models. We pointed out that if inflation happened in this false minimum,
      the Higgs boson mass has to be in the range 126.0+/-3.5  GeV, where ATLAS and CMS
      subsequently reported excesses of events. Here we show that for these values of
      the Higgs boson mass, the inflationary gravitational wave background has be
      discovered with a tensor-to-scalar ratio at hand of future experiments. We
      suggest that combining cosmological observations with measurements of the top
      quark and Higgs boson masses represent a further test of the hypothesis that the
      standard model false minimum was the source of inflation in the universe.

PMID- 23003025
TI  - Strong coupling isotropization of non-abelian plasmas simplified.
AB  - We study the isotropization of a homogeneous, strongly coupled, non-abelian
      plasma by means of its gravity dual. We compare the time evolution of a large
      number of initially anisotropic states as determined, on the one hand, by the
      full nonlinear Einstein's equations and, on the other, by the Einstein's
      equations linearized around the final equilibrium state. The linear approximation
      works remarkably well even for states that exhibit large anisotropies. For
      example, it predicts with a 20% accuracy the isotropization time, which is of the
      order of t(iso)?1/T, with T the final equilibrium temperature. We comment on
      possible extensions to less symmetric situations.

PMID- 23003027
TI  - Observation of reactor electron antineutrinos disappearance in the RENO
      experiment.
AB  - The RENO experiment has observed the disappearance of reactor electron
      antineutrinos, consistent with neutrino oscillations, with a significance of 4.9
      standard deviations. Antineutrinos from six 2.8  GW(th) reactors at the Yonggwang
      Nuclear Power Plant in Korea, are detected by two identical detectors located at
      294 and 1383 m, respectively, from the reactor array center. In the 229 d data
      taking period between 11 August 2011 and 26 March 2012, the far (near) detector
      observed 17102 (154088) electron antineutrino candidate events with a background
      fraction of 5.5% (2.7%). The ratio of observed to expected numbers of
      antineutrinos in the far detector is 0.920+/-0.009(stat)+/-0.014(syst). From this
      deficit, we determine sin(2)2theta(13)=0.113+/-0.013(stat)+/-0.019(syst) based on
      a rate-only analysis.

PMID- 23003026
TI  - Improved measurement of muon antineutrino disappearance in MINOS.
AB  - We report an improved measurement of nu(MU) disappearance over a distance of 735
      km using the MINOS detectors and the Fermilab Main Injector neutrino beam in a
      nu(MU)-enhanced configuration. From a total exposure of 2.95*10(20) protons on
      target, of which 42% have not been previously analyzed, we make the most precise
      measurement of Deltam2=[2.62(-0.28)(+0.31)(stat)+/-0.09(syst)]*10(-3)  eV2 and
      constrain the nu(MU) mixing angle sin2(2theta)>0.75 (90% C.L.). These values are
      in agreement with Deltam2 and sin2(2theta) measured for nu(MU), removing the
      tension reported in [P. Adamson et al. (MINOS), Phys. Rev. Lett. 107, 021801
      (2011).].

PMID- 23003029
TI  - Halo nucleus 11Be: a spectroscopic study via neutron transfer.
AB  - The best examples of halo nuclei, exotic systems with a diffuse nuclear cloud
      surrounding a tightly bound core, are found in the light, neutron-rich region,
      where the halo neutrons experience only weak binding and a weak, or no, potential
      barrier. Modern direct-reaction measurement techniques provide powerful probes of
      the structure of exotic nuclei. Despite more than four decades of these studies
      on the benchmark one-neutron halo nucleus 11Be, the spectroscopic factors for the
      two bound states remain poorly constrained. In the present work, the 10Be(d,p)
      reaction has been used in inverse kinematics at four beam energies to study the
      structure of 11Be. The spectroscopic factors extracted using the adiabatic model
      were found to be consistent across the four measurements and were largely
      insensitive to the optical potential used. The extracted spectroscopic factor for
      a neutron in an nlj=2s(1/2) state coupled to the ground state of 10Be is 0.71(5).
      For the first excited state at 0.32 MeV, a spectroscopic factor of 0.62(4) is
      found for the halo neutron in a 1p(1/2) state.

PMID- 23003030
TI  - Making the best of mixed-field orientation of polar molecules: a recipe for
      achieving adiabatic dynamics in an electrostatic field combined with laser
      pulses.
AB  - We have experimentally and theoretically investigated the mixed-field orientation
      of rotational-state-selected OCS molecules and achieved strong degrees of
      alignment and orientation. The applied moderately intense nanosecond laser pulses
      are long enough to adiabatically align molecules. However, in combination with a
      weak dc electric field, the same laser pulses result in nonadiabatic dynamics of
      the mixed-field orientation. These observations are fully explained by
      calculations employing both adiabatic and nonadiabatic (time-dependent) models.

PMID- 23003031
TI  - Attosecond-resolved evolution of a laser-dressed helium atom: interfering
      excitation paths and quantum phases.
AB  - Using high-order harmonic attosecond pulse trains, we investigate the
      photoionization dynamics and transient electronic structure of a helium atom in
      the presence of moderately strong (~10(12)  W cm(-2)) femtosecond laser pulses.
      We observe quantum interferences between photoexcitation paths from the ground
      state to different laser-dressed Floquet state components. As the intensity ramps
      on femtosecond time scales, we observe switching between ionization channels
      mediated by different atomic resonances. Using precision measurements of ion
      yields and photoelectron distributions, the quantum phase difference between
      interfering paths is extracted for each ionization channel and compared with
      simulations. Our results elucidate photoionization mechanisms in strong fields
      and open the doors for photoabsorption or photoionization control schemes.

PMID- 23003032
TI  - Anomalous nuclear quantum effects in ice.
AB  - One striking anomaly of water ice has been largely neglected and never explained.
      Replacing hydrogen (1H) by deuterium (2H) causes ice to expand, whereas the
      normal isotope effect is volume contraction with increased mass. Furthermore, the
      anomaly increases with temperature T, even though a normal isotope shift should
      decrease with T and vanish when T is high enough to use classical nuclear
      motions. In this study, we show that these effects are very well described by ab
      initio density-functional theory. Our theoretical modeling explains these
      anomalies, and allows us to predict and to experimentally confirm a counter
      effect, namely, that replacement of 16O by 18O causes a normal lattice
      contraction.

PMID- 23003033
TI  - Attosecond probe of valence-electron wave packets by subcycle sculpted laser
      fields.
AB  - We experimentally and theoretically demonstrate a self-referenced wave-function
      retrieval of a valence-electron wave packet during its creation by strong-field
      ionization with a sculpted laser field. Key is the control over interferences
      arising at different time scales. Our work shows that the measurement of subcycle
      electron wave-packet interference patterns can serve as a tool to retrieve the
      structure and dynamics of the valence-electron cloud in atoms on a sub-10-as time
      scale.

PMID- 23003034
TI  - Nonstoichiometric intensities in core photoelectron spectroscopy.
AB  - X-ray photoemission spectroscopy is used in a great variety of research fields;
      one observable is the sample's stoichiometry. The stoichiometry can be deduced
      based on the expectation that the ionization cross sections for innershell
      orbitals are independent of the molecular composition. Here we used chlorine
      substituted ethanes in the gas phase to investigate the apparent carbon
      stoichiometry. We observe a nonstoichiometric ratio for a wide range of photon
      energies, the ratio exhibits x-ray-absorption fine structure spectroscopy (EXAFS)
      like oscillations and hundreds of eV above the C1s ionization approaches a value
      far from 1. These effects can be accounted for by considering the scattering of
      the outgoing photoelectron, which we model by multiple-scattering EXAFS
      calculations, and by considering the effects of losses due to monopole shakeup
      and shakeoff and to intramolecular inelastic scattering processes.

PMID- 23003028
TI  - First measurement of chiral dynamics in pi- gamma -> pi- pi- pi+.
AB  - The COMPASS Collaboration at CERN has investigated the pi- gamma -> pi- pi- pi+
      reaction at center-of-momentum energy below five pion masses, sqrt[s]<5m(pi),
      embedded in the Primakoff reaction of 190 GeV pions impinging on a lead target.
      Exchange of quasireal photons is selected by isolating the sharp Coulomb peak
      observed at smallest momentum transfers, t'<0.001  GeV2/c2. Using partial-wave
      analysis techniques, the scattering intensity of Coulomb production described in
      terms of chiral dynamics and its dependence on the 3pi-invariant mass
      m(3pi)=sqrt[s] were extracted. The absolute cross section was determined in seven
      bins of sqrt[s] with an overall precision of 20%. At leading order, the result is
      found to be in good agreement with the prediction of chiral perturbation theory
      over the whole energy range investigated.

PMID- 23003035
TI  - Dipole-interaction-mediated laser cooling of polar molecules to ultracold
      temperatures.
AB  - We present a method to design a finite decay rate for excited rotational states
      in polar molecules. The setup is based on a hybrid system of polar molecules with
      atoms driven into a Rydberg state. The atoms and molecules are coupled via the
      strong dipolar exchange interaction between two rotation levels of the polar
      molecule and two Rydberg states. Such a controllable decay rate opens the way to
      optically pump the hyperfine levels of polar molecules and it enables the
      application of conventional laser cooling techniques for cooling polar molecules
      into quantum degeneracy.

PMID- 23003036
TI  - Atomic Rydberg reservoirs for polar molecules.
AB  - We discuss laser-dressed dipolar and van der Waals interactions between atoms and
      polar molecules, so that a cold atomic gas with laser admixed Rydberg levels acts
      as a designed reservoir for both elastic and inelastic collisional processes. The
      elastic scattering channel is characterized by large elastic scattering cross
      sections and repulsive shields to protect from close encounter collisions. In
      addition, we discuss a dissipative (inelastic) collision where a spontaneously
      emitted photon carries away (kinetic) energy of the collision partners, thus
      providing a significant energy loss in a single collision. This leads to the
      scenario of rapid thermalization and cooling of a molecule in the mK down to the
      MUK regime by cold atoms.

PMID- 23003037
TI  - Two-dimensional double-quantum spectra reveal collective resonances in an atomic
      vapor.
AB  - We report the observation of double-quantum coherence signals in a gas of
      potassium atoms at twice the frequency of the one-quantum coherences. Since a
      single atom does not have a state at the corresponding energy, this observation
      must be attributed to a collective resonance involving multiple atoms. These
      resonances are induced by weak interatomic dipole-dipole interactions, which
      means that the atoms cannot be treated in isolation, even at a low density of
      10(12)  cm(-3).

PMID- 23003038
TI  - Tailoring of keV-ion beams by image charge when transmitting through rhombic and
      rectangular shaped nanocapillaries.
AB  - We report on an unexpected effect of tailoring transmission profiles of Ne(7+)
      ions through nanocapillaries of rhombic and rectangular cross sections in mica.
      We find that capillaries of rhombic cross sections produce rectangular shaped ion
      transmission profiles and, vice versa, that capillaries of rectangular geometry
      give a rhombic beam shape. This shaping effect only occurs for transmitted ions
      and is absent for the small fraction of neutralized particles. The experimental
      findings and simulations of the projectile trajectories give clear evidence that
      the observed effect is due to the image forces experienced by the transmitting
      ions. This novel beam shaping mechanism suggests applications for the guiding,
      focusing, and shaping of ion beams.

PMID- 23003039
TI  - Trouble with the Lorentz law of force: incompatibility with special relativity
      and momentum conservation.
AB  - The Lorentz law of force is the fifth pillar of classical electrodynamics, the
      other four being Maxwell's macroscopic equations. The Lorentz law is the
      universal expression of the force exerted by electromagnetic fields on a volume
      containing a distribution of electrical charges and currents. If electric and
      magnetic dipoles also happen to be present in a material medium, they are
      traditionally treated by expressing the corresponding polarization and
      magnetization distributions in terms of bound-charge and bound-current densities,
      which are subsequently added to free-charge and free-current densities,
      respectively. In this way, Maxwell's macroscopic equations are reduced to his
      microscopic equations, and the Lorentz law is expected to provide a precise
      expression of the electromagnetic force density on material bodies at all points
      in space and time. This Letter presents incontrovertible theoretical evidence of
      the incompatibility of the Lorentz law with the fundamental tenets of special
      relativity. We argue that the Lorentz law must be abandoned in favor of a more
      general expression of the electromagnetic force density, such as the one
      discovered by Einstein and Laub in 1908. Not only is the Einstein-Laub formula
      consistent with special relativity, it also solves the long-standing problem of
      "hidden momentum" in classical electrodynamics.

PMID- 23003040
TI  - Experimental verification of displacement-current conduits in metamaterials
      inspired optical circuitry.
AB  - Electric displacement current is present in capacitors and optical waveguides;
      however, unlike the conduction current in metallic wires, it is not confined.
      Analogous to the contrast in conductivity between a metallic wire and the
      surrounding air, displacement-current wires based on near-zero permittivity media
      contain a large contrast in effective permittivity. As a variation on this idea,
      in this Letter, we demonstrate at microwave frequencies two displacement-current
      cables based on effectively negative and effectively positive permittivity
      metastructures. Our experimental results clearly show cablelike behaviors that
      allow bending of the structure while still confining and maintaining the
      primarily longitudinal forward and reverse effective displacement currents within
      each conduit. The results presented here experimentally verify the notion of
      displacement-current wires and cables in metatronics as metamaterial-inspired
      circuitry.

PMID- 23003041
TI  - Quasi-phase-matching high-harmonic radiation using chirped THz pulses.
AB  - High-order harmonic generation in the presence of a chirped THz pulse is
      investigated numerically with a complete 3D nonadiabatic model. The assisting THz
      pulse illuminates the high-order harmonic generation gas cell laterally inducing
      quasi-phase-matching. We demonstrate that it is possible to compensate the phase
      mismatch during propagation and extend the macroscopic cutoff of a propagated
      strong IR pulse to the single-dipole cutoff. We obtain 2 orders of magnitude
      increase in the harmonic efficiency of cutoff harmonics (~170  eV) using a THz
      pulse of constant wavelength, and a further factor of 3 enhancement when a
      chirped THz pulse is used.

PMID- 23003042
TI  - Loss-induced omnidirectional bending to the normal in epsilon-near-zero
      metamaterials.
AB  - Contrary to conventional wisdom that light bends away from the normal when it
      passes from high to low refractive index media, here we demonstrate an exotic
      phenomenon that the direction of electromagnetic power can bend toward the normal
      when light is incident from an arbitrary high refractive index medium (or air) to
      a epsilon-near-zero (ENZ) metamaterial. Moreover, the direction of the
      transmission is close to the normal for all angles of incidence. This anti
      Snell's law refraction results from the interplay between ENZ and material loss.
      The loss can increase the transmission at the air-ENZ interface and collimate the
      beam inside the ENZ medium. Furthermore, in an ideal loss configuration, the
      propagation loss in anisotropic ENZ materials can approach zero when the material
      loss goes to infinity.

PMID- 23003043
TI  - Hyperbolic chaos of Turing patterns.
AB  - We consider time evolution of Turing patterns in an extended system governed by
      an equation of the Swift-Hohenberg type, where due to an external periodic
      parameter modulation longwave and shortwave patterns with length scales related
      as 1:3 emerge in succession. We show theoretically and demonstrate numerically
      that the spatial phases of the patterns, being observed stroboscopically, are
      governed by an expanding circle map, so that the corresponding chaos of Turing
      patterns is hyperbolic, associated with a strange attractor of the Smale-Williams
      solenoid type. This chaos is shown to be robust with respect to variations of
      parameters and boundary conditions.

PMID- 23003044
TI  - Graphical notation reveals topological stability criteria for collective dynamics
      in complex networks.
AB  - We propose a graphical notation by which certain spectral properties of complex
      systems can be rewritten concisely and interpreted topologically. Applying this
      notation to analyze the stability of a class of networks of coupled dynamical
      units, we reveal stability criteria on all scales. In particular, we show that in
      systems such as the Kuramoto model the Coates graph of the Jacobian matrix must
      contain a spanning tree of positive elements for the system to be locally stable.

PMID- 23003045
TI  - Mechanical evidence of the orbital angular momentum to energy ratio of vortex
      beams.
AB  - We measure, in a single experiment, both the radiation pressure and the torque
      due to a wide variety of propagating acoustic vortex beams. The results validate,
      for the first time directly, the theoretically predicted ratio of the orbital
      angular momentum to linear momentum in a propagating beam. We experimentally
      determine this ratio using simultaneous measurements of both the levitation force
      and the torque on an acoustic absorber exerted by a broad range of helical
      ultrasonic beams produced by a 1000-element matrix transducer array. In general,
      beams with helical phase fronts have been shown to contain orbital angular
      momentum as the result of the azimuthal component of the Poynting vector around
      the propagation axis. Theory predicts that for both optical and acoustic helical
      beams the ratio of the angular momentum current of the beam to the power should
      be given by the ratio of the beam's topological charge to its angular frequency.
      This direct experimental observation that the ratio of the torque to power does
      convincingly match the expected value (given by the topological charge to angular
      frequency ratio of the beam) is a fundamental result.

PMID- 23003046
TI  - Incompressible wave motion of compressible fluids.
AB  - We consider linear waves in compressible fluids in a uniform potential field,
      such as a gravity field, and demonstrate that a particular type of wave motion,
      in which pressure remains constant in each fluid parcel, is supported by
      inhomogeneous fluids occupying bounded or unbounded domains. We present
      elementary, exact solutions of linearized hydrodynamics equations, which describe
      the new type of waves in the coupled ocean-atmosphere system. The solutions
      provide an extension of surface gravity waves in an incompressible fluid half
      space with a free boundary to waves in compressible, three-dimensionally
      inhomogeneous, rotating fluids.

PMID- 23003047
TI  - Spontaneous breaking of the spatial homogeneity symmetry in wave turbulence.
AB  - We report a surprising new result for wave turbulence which may have broader
      ramifications for general turbulence theories. Spatial homogeneity, the symmetry
      property that all statistical moments are functions only of the relative geometry
      of any configuration of points, can be spontaneously broken by the instability of
      the finite flux Kolmogorov-Zakharov spectrum in certain (usually one dimensional)
      situations. As a result, the nature of the statistical attractor changes
      dramatically, from a sea of resonantly interacting dispersive waves to an
      ensemble of coherent radiating pulses.

PMID- 23003048
TI  - Large charge extraction from metallic multifilamentary Nb3Sn photocathode.
AB  - The current density limit for photoemission from metals was measured in an rf
      photogun to be below 10(9)  A/m2. We have achieved 1.6*10(11)  A/m2 by photofield
      emission from a new type of photocathode made from a metallic-composite,
      multifilamentary Nb3Sn wire driven by a 266 nm picosecond laser pulse and a 2 ns,
      50 kV accelerating voltage. This cathode has a micrometer arrayed structure with
      tens of thousands of Nb/Nb3Sn filaments embedded in a bronze matrix. Our
      measurements revealed the existence of a new electron emission regime at high
      laser fluence (100  mJ/cm2). We have extracted stably, and without any surface
      ablation, up to 4800 pC of charge. This corresponds to 0.9% quantum efficiency,
      100 times larger than what is measured from conventional metallic photocathodes.
      The unexpected large and stable charge extraction cannot be explained by the 3
      step model. Thanks to the small emitting area, the measured emittance (0.6 
      mm.mrad) is low in spite of the high current density and space charge effects.
      This cathode will be of benefit for many applications based on short and bright
      electron bunches.

PMID- 23003049
TI  - High-power gamma-ray flash generation in ultraintense laser-plasma interactions.
AB  - When high-intensity laser interaction with matter enters the regime of dominated
      radiation reaction, the radiation losses open the way for producing short pulse
      high-power gamma-ray flashes. The gamma-ray pulse duration and divergence are
      determined by the laser pulse amplitude and by the plasma target density scale
      length. On the basis of theoretical analysis and particle-in-cell simulations
      with the radiation friction force incorporated, optimal conditions for generating
      a gamma-ray flash with a tailored overcritical density target are found.

PMID- 23003050
TI  - Experiment in planar geometry for shock ignition studies.
AB  - The capacity to launch a strong shock wave in a compressed target in the presence
      of large preplasma has been investigated experimentally and numerically in a
      planar geometry. The experiment was performed on the LULI 2000 laser facility
      using one laser beam to compress the target and a second to launch the strong
      shock simulating the intensity spike in the shock ignition scheme. Thanks to a
      large set of diagnostics, it has been possible to compare accurately experimental
      results with 2D numerical simulations. A good agreement has been observed even if
      a more detailed study of the laser-plasma interaction for the spike is necessary
      in order to confirm that this scheme is a possible alternative for inertial
      confinement fusion.

PMID- 23003051
TI  - Mitigating laser imprint in direct-drive inertial confinement fusion implosions
      with high-Z dopants.
AB  - Nonuniformities seeded by both long- and short-wavelength laser perturbations can
      grow via Rayleigh-Taylor (RT) instability in direct-drive inertial confinement
      fusion, leading to performance reduction in low-adiabat implosions. To mitigate
      the effect of laser imprinting on target performance, spherical RT experiments
      have been performed on OMEGA using Si- or Ge-doped plastic targets in a cone-in
      shell configuration. Compared to a pure plastic target, radiation preheating from
      these high-Z dopants (Si/Ge) increases the ablation velocity and the standoff
      distance between the ablation front and laser-deposition region, thereby reducing
      both the imprinting efficiency and the RT growth rate. Experiments showed a
      factor of 2-3 reduction in the laser-imprinting efficiency and a reduced RT
      growth rate, leading to significant (3-5 times) reduction in the sigma(rms) of
      shell rhoR modulation for Si- or Ge-doped targets. These features are reproduced
      by radiation-hydrodynamics simulations using the two-dimensional hydrocode DRACO.

PMID- 23003052
TI  - Kelvin-Helmholtz turbulence associated with collisionless shocks in laser
      produced plasmas.
AB  - We report the experimental results of a turbulent electric field driven by Kelvin
      Helmholtz instability associated with laser produced collisionless shock waves.
      By irradiating an aluminum double plane target with a high-power laser,
      counterstreaming plasma flows are generated. As the consequence of the two plasma
      interactions, two shock waves and the contact surface are excited. The shock
      electric field and transverse modulation of the contact surface are observed by
      proton radiography. Performing hydrodynamic simulations, we reproduce the time
      evolutions of the reverse shocks and the transverse modulation driven by Kelvin
      Helmholtz instability.

PMID- 23003053
TI  - Bose gases near unitarity.
AB  - We study the properties of strongly interacting Bose gases at the density and
      temperature regime when the three-body recombination rate is substantially
      reduced. In this regime, one can have a Bose gas with all particles in scattering
      states (i.e., the "upper branch") with little loss even at unitarity over the
      duration of the experiment. We show that because of bosonic enhancement, pair
      formation is shifted to the atomic side of the original resonance (where
      scattering length a(s)<0), opposite to the fermionic case. In a trap, a repulsive
      Bose gas remains mechanically stable when brought across resonance to the atomic
      side until it reaches a critical scattering length a(s)*<0. For a(s)<a(s)*, the
      density consists of a core of upper branch bosons surrounded by an outer layer of
      equilibrium branch. The conditions of low three-body recombination require that
      the particle number N<1.024(T/omega)(5/2) in a harmonic trap with frequency
      omega.

PMID- 23003054
TI  - Distinct configurations of antisite defects in ordered metal phosphates:
      comparison between LiMnPO4 and LiFePO4.
AB  - By using a combination of aberration-corrected high-angle annular dark-field
      scanning transmission electron microscopy, ab initio density-functional theory
      calculations, and neutron powder diffraction techniques, We have found completely
      different configurations of the antisite exchange defects in LiMnPO4 and LiFePO4,
      with a random distribution of the exchange pairs without aggregation in the
      former and with zigzag-type clustering behavior preferred in the latter.
      Recalling the compositional analogy and identical crystal structure of the two
      metal phosphates, such unexpectedly distinct arrangement of the same type of
      point defects is a notable structural aspect.

PMID- 23003055
TI  - Influence of the narrow {111} planes on axial and planar ion channeling.
AB  - We report channeling patterns where clearly resolved effects of the narrow {111}
      planes are observed in axial and planar alignments for 2 MeV protons passing
      through a 55 nm [001] silicon membrane. At certain axes, such as <213> and <314>,
      the offset in atomic rows forming the narrow {111} planes results in shielding
      from the large potential at the wide {111} planes, producing a region of shallow,
      asymmetric potential from which axial channeling patterns have no plane of
      symmetry. At small tilts from such axes, different behavior is observed from the
      wide and narrow {111} planes. At planar alignment, distinctive channeling effects
      due to the narrow planes are observed. As a consequence of the shallow potential
      well at the narrow planes, incident protons suffer dechanneled trajectories which
      are excluded from channeling within the wide planes, resulting in an anomalously
      large scattered beam at {111} alignment.

PMID- 23003056
TI  - Evidence of correlation between catalyst particles and the single-wall carbon
      nanotube diameter: a first step towards chirality control.
AB  - Controlling the structure of single-wall carbon nanotubes during their synthesis
      by chemical vapor deposition remains a challenging issue. Here, using a specific
      synthesis protocol and ex situ transmission electron microscopy, we perform a
      statistical analysis of the structure of the tubes and of the catalyst particles
      from which they grow. We discriminate two nucleation modes, corresponding to
      different nanotube-particle junctions, that occur independently of the particle
      size. With the support of tight binding calculations, we show that a direct
      control of the nanotube diameter by the particle can only be achieved under
      growth conditions close to thermodynamic equilibrium.

PMID- 23003057
TI  - Role of antisite disorder on preamorphization swelling in titanate pyrochlores.
AB  - Ion irradiation experiments and atomistic simulations were used to demonstrate
      that irradiation-induced lattice swelling in a complex oxide, Lu2Ti2O7, is due
      initially to the formation of cation antisite defects. X-ray diffraction revealed
      that cation antisite formation correlates directly with lattice swelling and
      indicates that the volume per antisite pair is approximately 12  A3. First
      principles calculations revealed that lattice swelling is best explained by
      cation antisite defects. Temperature accelerated dynamics simulations indicate
      that cation Frenkel defects are metastable and decay to form antisite defects.

PMID- 23003058
TI  - Nanoscale structure and structural relaxation in Zr50Cu45Al5 bulk metallic glass.
AB  - Hybrid reverse Monte Carlo simulations of the structure of Zr50Cu45Al5 bulk
      metallic glass incorporating medium-range structure from fluctuation electron
      microscopy data and short-range structure from an embedded atom potential produce
      structures with significant fractions of icosahedral- and crystal-like atomic
      clusters. Similar clusters group together into nanometer-scale regions, and
      relaxation transforms crystal-like clusters into icosahedral clusters. A model
      refined against only the potential does not agree with the fluctuation microscopy
      data and contains few crystal-like clusters.

PMID- 23003059
TI  - Te-centric view of the phase change mechanism in Ge-Sb-Te alloys.
AB  - The short-range structure of amorphous and fcc Ge1Sb2Te4 and Ge2Sb2Te5 phase
      change alloys is investigated using 125Te NMR spectroscopy. Both amorphous and
      fcc structures consist solely of heteropolar Ge/Sb-Te bonds that may enable rapid
      displacive phase transformation without the need for extensive atomic
      rearrangement. The vacancy distribution is random in microcrystalline fcc phases
      while significant clustering is observed in their nanocrystalline counterparts
      that may result in the formation of tetrahedrally coordinated Ge atoms in the
      latter. This structural commonality may further facilitate the kinetics of
      transformation between amorphous and nanocrystalline fcc phases, a situation
      relevant for high-density memory storage.

PMID- 23003060
TI  - Ordered arrays of size-selected oxide nanoparticles.
AB  - A bottom-up approach to produce a long-range ordered superlattice of monodisperse
      and isomorphic metal-oxide nanoparticles (NP) supported onto an oxide substrate
      is demonstrated. The synthetic strategy consists of self-assembling metallic NP
      on an ultrathin nanopatterned aluminum oxide template followed by a morphology
      conserving oxidation process, and is exemplified in the case of Ni, but is
      generally applicable to a wide range of metallic systems. Both fully oxidized and
      core-shell metal-metal-oxide particles are synthesized, up to 3-4 nm in diameter,
      and characterized via spectroscopic and theoretical tools. This opens up a new
      avenue for probing unit and ensemble effects on the properties of oxide materials
      in the nanoscale regime.

PMID- 23003061
TI  - Atomic mechanism of flow in simple liquids under shear.
AB  - Atomic correlations in a simple liquid in steady-state flow under shear stress
      are studied by molecular dynamics simulation. The local atomic level strain is
      determined through the anisotropic pair-density function. The atomic level strain
      has a limited spatial extension whose range is dependent on the strain rate and
      extrapolates to zero at the critical strain rate. A failure event is identified
      with altering the local topology of atomic connectivity by exchanging bonds among
      neighboring atoms.

PMID- 23003062
TI  - Toughening and asymmetry in peeling of heterogeneous adhesives.
AB  - The effective adhesive properties of heterogeneous thin films are characterized
      through a combined experimental and theoretical investigation. By bridging
      scales, we show how variations of elastic or adhesive properties at the
      microscale can significantly affect the effective peeling behavior of the
      adhesive at the macroscale. Our study reveals three elementary mechanisms in
      heterogeneous systems involving front propagation: (i) patterning the elastic
      bending stiffness of the film produces fluctuations of the driving force
      resulting in dramatically enhanced resistance to peeling; (ii) optimized
      arrangements of pinning sites with large adhesion energy are shown to control the
      effective system resistance, allowing the design of highly anisotropic and
      asymmetric adhesives; (iii) heterogeneities of both types result in front motion
      instabilities producing sudden energy releases that increase the overall adhesion
      energy. These findings open potentially new avenues for the design of thin films
      with improved adhesion properties, and motivate new investigations of other
      phenomena involving front propagation.

PMID- 23003063
TI  - Accurate measurement of electron beam induced displacement cross sections for
      single-layer graphene.
AB  - We present an accurate measurement and a quantitative analysis of electron-beam
      induced displacements of carbon atoms in single-layer graphene. We directly
      measure the atomic displacement ("knock-on") cross section by counting the lost
      atoms as a function of the electron-beam energy and applied dose. Further, we
      separate knock-on damage (originating from the collision of the beam electrons
      with the nucleus of the target atom) from other radiation damage mechanisms
      (e.g., ionization damage or chemical etching) by the comparison of ordinary (12C)
      and heavy (13C) graphene. Our analysis shows that a static lattice approximation
      is not sufficient to describe knock-on damage in this material, while a very good
      agreement between calculated and experimental cross sections is obtained if
      lattice vibrations are taken into account.

PMID- 23003064
TI  - Dielectric breakdown in spin-polarized Mott insulator.
AB  - Nonlinear response of a Mott insulator to external electric field, corresponding
      to dielectric breakdown phenomenon, is studied within of a one-dimensional half
      filled Hubbard model. It is shown that in the limit of nearly spin-polarized
      insulator the decay rate of the ground state into excited holon-doublon pair can
      be evaluated numerically as well to high accuracy analytically. Results show that
      the threshold field depends on the charge gap as F(th)?Delta(3/2). Numerical
      results on small systems indicate on the persistence of a similar mechanism for
      the breakdown for decreasing magnetization down to unpolarized system.

PMID- 23003065
TI  - General relationship between the entanglement spectrum and the edge state
      spectrum of topological quantum states.
AB  - We consider (2+1)-dimensional topological quantum states which possess edge
      states described by a chiral (1+1)-dimensional conformal field theory, such as,
      e.g., a general quantum Hall state. We demonstrate that for such states the
      reduced density matrix of a finite spatial region of the gapped topological state
      is a thermal density matrix of the chiral edge state conformal field theory which
      would appear at the spatial boundary of that region. We obtain this result by
      applying a physical instantaneous cut to the gapped system and by viewing the
      cutting process as a sudden "quantum quench" into a conformal field theory, using
      the tools of boundary conformal field theory. We thus provide a demonstration of
      the observation made by Li and Haldane about the relationship between the
      entanglement spectrum and the spectrum of a physical edge state.

PMID- 23003066
TI  - Quantum oscillations from nodal bilayer magnetic breakdown in the underdoped high
      temperature superconductor YBa2Cu3O(6+x).
AB  - We report quantum oscillations in underdoped YBa2Cu3O6.56 over a significantly
      large range in magnetic field extending from ~24 to 101 T, enabling three well
      spaced low frequencies at ~440+/-10, 532+/-2, and 620+/-10  T to be clearly
      resolved. We show that a small nodal bilayer coupling that splits a nodal pocket
      into bonding and antibonding orbits yields a sequence of frequencies, F0-DeltaF,
      F0, and F0+DeltaF and accompanying beat pattern similar to that observed
      experimentally, on invoking magnetic breakdown tunneling at the nodes. The
      relative amplitudes of the multiple frequencies observed experimentally in
      quantum oscillation measurements are shown to be reproduced using a value of
      nodal bilayer gap quantitatively consistent with that measured in photoemission
      experiments in the underdoped regime.

PMID- 23003067
TI  - Microscopic origin of universal quasilinear band structures of transparent
      conducting oxides.
AB  - A tight-binding-based microscopic theory is developed that accounts for
      quasilinear conduction bands appearing commonly in transparent conducting oxides.
      It is found that the interaction between oxygen p and metal s orbtials plays a
      critical role in determining the band structure around the conduction-band
      minimum. Under certain types of short-range orders, the tight-binding model
      universally leads to a dispersion relation which corresponds to that of the
      massive Dirac particle. The impact of the graphenelike band structure is
      demonstrated by evaluating the electron mobility of highly doped n-type ZnO.

PMID- 23003068
TI  - Observations of Co4+ in a higher spin state and the increase in the Seebeck
      coefficient of thermoelectric Ca3Co4O9.
AB  - Ca3Co4O9 has a unique structure that leads to exceptionally high thermoelectric
      transport. Here we report the achievement of a 27% increase in the room
      temperature in-plane Seebeck coefficient of Ca3Co4O9 thin films. We combine
      aberration-corrected Z-contrast imaging, atomic-column resolved electron energy
      loss spectroscopy, and density-functional calculations to show that the increase
      is caused by stacking faults with Co4+-ions in a higher spin state compared to
      that of bulk Ca3Co4O9. The higher Seebeck coefficient makes the Ca3Co4O9 system
      suitable for many high temperature waste-heat-recovery applications.

PMID- 23003069
TI  - Storage of classical information in quantum spins.
AB  - Digital magnetic recording is based on the storage of a bit of information in the
      orientation of a magnetic system with two stable ground states. Here we address
      two fundamental problems that arise when this is done on a quantized spin:
      quantum spin tunneling and backaction of the readout process. We show that
      fundamental differences exist between integer and semi-integer spins when it
      comes to both reading and recording classical information in a quantized spin.
      Our findings imply fundamental limits to the miniaturization of magnetic bits and
      are relevant to recent experiments where a spin-polarized scanning tunneling
      microscope reads and records a classical bit in the spin orientation of a single
      magnetic atom.

PMID- 23003070
TI  - Direct observation of interband spin-orbit coupling in a two-dimensional electron
      system.
AB  - We report the direct observation of interband spin-orbit (SO) coupling in a two
      dimensional (2D) surface electron system, in addition to the anticipated Rashba
      spin splitting. Using angle-resolved photoemission experiments and first
      principles calculations on Bi-Ag-Au heterostructures, we show that the effect
      strongly modifies the dispersion as well as the orbital and spin character of the
      2D electronic states, thus giving rise to considerable deviations from the Rashba
      model. The strength of the interband SO coupling is tuned by the thickness of the
      thin film structures.

PMID- 23003071
TI  - Coupled spin and valley physics in monolayers of MoS2 and other group-VI
      dichalcogenides.
AB  - We show that inversion symmetry breaking together with spin-orbit coupling leads
      to coupled spin and valley physics in monolayers of MoS2 and other group-VI
      dichalcogenides, making possible controls of spin and valley in these 2D
      materials. The spin-valley coupling at the valence-band edges suppresses spin and
      valley relaxation, as flip of each index alone is forbidden by the valley
      contrasting spin splitting. Valley Hall and spin Hall effects coexist in both
      electron-doped and hole-doped systems. Optical interband transitions have
      frequency-dependent polarization selection rules which allow selective
      photoexcitation of carriers with various combination of valley and spin indices.
      Photoinduced spin Hall and valley Hall effects can generate long lived spin and
      valley accumulations on sample boundaries. The physics discussed here provides a
      route towards the integration of valleytronics and spintronics in multivalley
      materials with strong spin-orbit coupling and inversion symmetry breaking.

PMID- 23003072
TI  - Electron quantum optics: partitioning electrons one by one.
AB  - We have realized a quantum optics like Hanbury Brown-Twiss (HBT) experiment by
      partitioning, on an electronic beam splitter, single elementary electronic
      excitations produced one by one by an on-demand emitter. We show that the
      measurement of the output currents correlations in the HBT geometry provides a
      direct counting, at the single charge level, of the elementary excitations
      (electron-hole pairs) generated by the emitter at each cycle. We observe the
      antibunching of low energy excitations emitted by the source with thermal
      excitations of the Fermi sea already present in the input leads of the splitter,
      which suppresses their contribution to the partition noise. This effect is used
      to probe the energy distribution of the emitted wave packets.

PMID- 23003073
TI  - Electric-field-induced Majorana fermions in armchair carbon nanotubes.
AB  - We consider theoretically an armchair carbon nanotube (CNT) in the presence of an
      electric field and in contact with an s-wave superconductor. We show that the
      proximity effect opens up superconducting gaps in the CNT of different strengths
      for the exterior and interior branches of the two Dirac points. For strong
      proximity induced superconductivity the interior gap can be of the p-wave type,
      while the exterior gap can be tuned by the electric field to be of the s-wave
      type. Such a setup supports a single Majorana bound state at each end of the CNT.
      In the case of a weak proximity induced superconductivity, the gaps in both
      branches are of the p-wave type. However, the temperature can be chosen in such a
      way that the smallest gap is effectively closed. Using renormalization group
      techniques we show that the Majorana bound states exist even after taking into
      account electron-electron interactions.

PMID- 23003075
TI  - Connection of edge states to bulk topological invariance in a quantum spin Hall
      state.
AB  - We propose a topological understanding of general characteristics of edge states
      in a quantum spin Hall phase without considering any symmetries. It follows from
      the requirement of gauge invariance that either the energy gap or the gap in the
      spectrum of the projected spin operator needs to close on the sample edges. Based
      upon the Kane-Mele model with a uniform Zeeman field and a smooth confining
      potential near the sample boundaries, we demonstrate the existence of gapless
      edge states in the absence of time-reversal symmetry and their robust properties
      against impurities. These gapless edge states are protected by the band topology
      alone, rather than any symmetries.

PMID- 23003074
TI  - Enhancement of the nu = 5/2 fractional quantum Hall state in a small in-plane
      magnetic field.
AB  - Using a 50-nm-width ultraclean GaAs/AlGaAs quantum well, we have studied the
      Landau level filling factor nu=5/2 fractional quantum Hall effect in a
      perpendicular magnetic field B~1.7  T and determined its dependence on tilted
      magnetic fields. Contrary to all previous results, the 5/2 resistance minimum and
      the Hall plateau are found to strengthen continuously under an increasing tilt
      angle 0<theta<25 degrees  (corresponding to an in-plane magnetic field 0<B(?)<0.8
      T). In the same range of theta, the activation gaps of both the 7/3 and the 8/3
      states are found to increase with tilt. The 5/2 state transforms into a
      compressible Fermi liquid upon tilt angle theta>60 degrees , and the composite
      fermion series [2+p/(2p+/-1), p=1,2] can be identified. Based on our results, we
      discuss the relevance of a Skyrmion spin texture at nu=5/2 associated with small
      Zeeman energy in wide quantum wells, as proposed by Wojs et al. [Phys. Rev. Lett.
      104, 086801 (2010)].

PMID- 23003076
TI  - Impact of small-angle scattering on ballistic transport in quantum dots.
AB  - Disorder increasingly affects performance as electronic devices are reduced in
      size. The ionized dopants used to populate a device with electrons are
      particularly problematic, leading to unpredictable changes in the behavior of
      devices such as quantum dots each time they are cooled for use. We show that a
      quantum dot can be used as a highly sensitive probe of changes in disorder
      potential and that, by removing the ionized dopants and populating the dot
      electrostatically, its electronic properties become reproducible with high
      fidelity after thermal cycling to room temperature. Our work demonstrates that
      the disorder potential has a significant, perhaps even dominant, influence on the
      electron dynamics, with important implications for "ballistic" transport in
      quantum dots.

PMID- 23003077
TI  - Pressure-driven quantum criticality in iron-selenide superconductors.
AB  - We report a finding of a pressure-induced quantum critical transition in
      K0.8Fe(x)Se2 (x = 1.7 and 1.78) superconductors through in situ high-pressure
      electrical transport and x-ray diffraction measurements in diamond anvil cells.
      Transitions from metallic Fermi liquid behavior to non-Fermi liquid behavior and
      from antiferromagnetism to paramagnetism are found in the pressure range of 9.2
      10.3 GPa, in which superconductivity tends to disappear. The change around the
      quantum critical point from the coexisting antiferromagnetism state and the Fermi
      liquid behavior to the paramagnetism state and the non-Fermi liquid behavior in
      the iron-selenide superconductors demonstrates a unique mechanism for their
      quantum critical transition.

PMID- 23003078
TI  - Long-range proximity effect for opposite-spin pairs in superconductor-ferromagnet
      heterostructures under nonequilibrium quasiparticle distribution.
AB  - By now it is known that in a singlet superconductor-ferromagnet (S-F) structure
      the superconducting correlations carried by opposite-spin pairs penetrate into
      the ferromagnet over a short distance of the order of magnetic coherence length.
      The long-range proximity effect (LRPE), taking place on the length scale of the
      normal metal coherence length, can only be maintained by equal-spin pairs, which
      can be generated by magnetic inhomogeneities in the system. In this Letter, we
      have predicted a new type of LRPE, which can take place in S-F heterostructures
      under nonequilibrium conditions. The superconducting correlations in the F region
      are generated by opposite-spin Cooper pairs and equal-spin pairs are not
      involved. The possibility for an opposite-spin pair to penetrate into the
      ferromagnet over a large distance is provided by creation of the proper
      nonequilibrium quasiparticle distribution there. This leads to a sharp increase
      (up to a few orders of magnitude) of the critical Josephson current through a S-F
      S junction at some values of the voltage controlling the nonequilibrium
      distribution in the F interlayer.

PMID- 23003079
TI  - Magnetic proximity effect in YBa2Cu3O7/La(2/3)Ca(1/3)MnO3 and
      YBa2Cu3O7/LaMnO(3+delta) superlattices.
AB  - Using neutron reflectometry and resonant x-ray techniques we studied the magnetic
      proximity effect (MPE) in superlattices composed of superconducting YBa2Cu3O7 and
      ferromagnetic-metallic La0.67Ca0.33MnO3 or ferromagnetic-insulating
      LaMnO(3+delta). We find that the MPE strongly depends on the electronic state of
      the manganite layers, being pronounced for the ferromagnetic-metallic
      La0.67Ca0.33MnO3 and almost absent for ferromagnetic-insulating LaMnO(3+delta).
      We also detail the change of the magnetic depth profile due to the MPE and
      provide evidence for its intrinsic nature.

PMID- 23003080
TI  - Origin of the high Neel temperature in SrTcO3.
AB  - We investigate the origin of the high Neel temperature recently found in Tc4+
      perovskites. The electronic structure in the magnetic state of SrTcO3 and its 3d
      analogue SrMnO3 is calculated within a framework combining band-structure and
      many-body methods. In agreement with experiment, for SrTcO3 a smaller magnetic
      moment and 4 times larger Neel temperature are found. We show that this is
      because the Tc compound lies on the verge of the itinerant-to-localized
      transition, while the Mn compound lies deeper into the localized side. For SrTcO3
      we predict that the Neel temperature depends weakly on applied pressure, in clear
      violation of Bloch's rule, signaling the complete breakdown of the localized
      picture.

PMID- 23003081
TI  - Voltage-induced ferromagnetic resonance in magnetic tunnel junctions.
AB  - We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB magnetic
      tunnel junctions (MTJs) by the combined action of voltage-controlled magnetic
      anisotropy (VCMA) and spin transfer torque (ST). Our measurements reveal that GHz
      frequency VCMA torque and ST in low-resistance MTJs have similar magnitudes, and
      thus that both torques are equally important for understanding high-frequency
      voltage-driven magnetization dynamics in MTJs. As an example, we show that VCMA
      can increase the sensitivity of an MTJ-based microwave signal detector to the
      sensitivity level of semiconductor Schottky diodes.

PMID- 23003082
TI  - Information transfer by vector spin chirality in finite magnetic chains.
AB  - Vector spin chirality is one of the fundamental characteristics of complex
      magnets. For a one-dimensional spin-spiral state it can be interpreted as the
      handedness, or rotational sense of the spiral. Here, using spin-polarized
      scanning tunneling microscopy, we demonstrate the occurrence of an atomic-scale
      spin spiral in finite individual bi-atomic Fe chains on the (5*1)-Ir(001)
      surface. We show that the broken inversion symmetry at the surface promotes one
      direction of the vector spin chirality, leading to a unique rotational sense of
      the spiral in all chains. Correspondingly, changes in the spin direction of one
      chain end can be probed tens of nanometers away, suggesting a new way of
      transmitting information about the state of magnetic objects on the nanoscale.

PMID- 23003083
TI  - Magnon lifetimes on the Fe(110) surface: the role of spin-orbit coupling.
AB  - We provide direct experimental evidence which demonstrates that, in the presence
      of a large spin-orbit coupling, the lifetime, amplitude, group, and phase
      velocity of the magnons propagating along two opposite (but crystallographically
      equivalent) directions perpendicular to the magnetization are different. A real
      time and space representation reveals that magnons with the same energy
      (eigenfrequency) propagate differently along two opposite directions. Our
      findings can inspire ideas for designing new spintronic devices.

PMID- 23003084
TI  - Switching magnetization by 180 degrees  with an electric field.
AB  - Magnetoelectric coupling allows for manipulating the magnetization by an external
      electric field or the electrical polarization by an external magnetic field.
      Here, we propose a mechanism to electrically induce 180 degrees  magnetization
      switching combining two effects: the magnetoelectric coupling at a multiferroic
      interface and magnetic interlayer exchange coupling. By means of first-principles
      methods, we investigate a ferroelectric layer in contact with a Fe/Au/Fe
      trilayer. The calculations show that the interface magnetism is strongly coupled
      to the ferroelectric layer. Furthermore, under certain conditions a reversal of
      polarization causes a sign reversal of the interlayer exchange coupling which is
      results in a 180 degrees  switching of the free layer magnetization. We argue
      that this magnetoelectric coupling mechanism is very robust and can find
      applications in magnetic data storage.

PMID- 23003085
TI  - First-principles prediction of metal-free magnetism and intrinsic half
      metallicity in graphitic carbon nitride.
AB  - Transition metal-free magnetism and half-metallicity recently has been the
      subject of intense research activity due to its potential in spintronics
      application. Here we, for the first time, demonstrate via density functional
      theory that the most recently experimentally realized graphitic carbon nitride (g
      C4N3) displays a ferromagnetic ground state. Furthermore, this novel material is
      predicted to possess an intrinsic half-metallicity never reported to date. Our
      results highlight a new promising material toward realistic metal-free
      spintronics application.

PMID- 23003086
TI  - Vertical cavity surface emitting terahertz laser.
AB  - Vertical cavity surface emitting terahertz lasers can be realized in conventional
      semiconductor microcavities with embedded quantum wells in the strong coupling
      regime. The cavity is to be pumped optically at half the frequency of the 2p
      exciton state. Once a threshold population of 2p excitons is achieved, a
      stimulated terahertz transition populates the lower exciton-polariton branch, and
      the cavity starts emitting laser light both in the optical and terahertz ranges.
      The lasing threshold is sensitive to the statistics of photons of the pumping
      light.

PMID- 23003087
TI  - Electrical control of interdot electron tunneling in a double InGaAs quantum-dot
      nanostructure.
AB  - We employ ultrafast pump-probe spectroscopy to directly monitor electron
      tunneling between discrete orbital states in a pair of spatially separated
      quantum dots. Immediately after excitation, several peaks are observed in the
      pump-probe spectrum due to Coulomb interactions between the photogenerated charge
      carriers. By tuning the relative energy of the orbital states in the two dots and
      monitoring the temporal evolution of the pump-probe spectra the electron and hole
      tunneling times are separately measured and resonant tunneling between the two
      dots is shown to be mediated both by elastic and inelastic processes. Ultrafast
      (<5  ps) interdot tunneling is shown to occur over a surprisingly wide bandwidth,
      up to ~8  meV, reflecting the spectrum of exciton-acoustic phonon coupling in the
      system.

PMID- 23003088
TI  - Dynamic nuclear spin polarization in the resonant laser excitation of an InGaAs
      quantum dot.
AB  - Resonant optical excitation of lowest-energy excitonic transitions in self
      assembled quantum dots leads to nuclear spin polarization that is qualitatively
      different from the well-known optical orientation phenomena. By carrying out a
      comprehensive set of experiments, we demonstrate that nuclear spin polarization
      manifests itself in quantum dots subjected to finite external magnetic field as
      locking of the higher energy Zeeman transition to the driving laser field, as
      well as the avoidance of the resonance condition for the lower energy Zeeman
      branch. We interpret our findings on the basis of dynamic nuclear spin
      polarization originating from noncollinear hyperfine interaction and find
      excellent agreement between experiment and theory. Our results provide evidence
      for the significance of noncollinear hyperfine processes not only for nuclear
      spin diffusion and decay, but also for buildup dynamics of nuclear spin
      polarization in a coupled electron-nuclear spin system.

PMID- 23003089
TI  - Temperature- and magnetic-field-dependent longitudinal spin relaxation in
      nitrogen-vacancy ensembles in diamond.
AB  - We present an experimental study of the longitudinal electron-spin relaxation
      time (T1) of negatively charged nitrogen-vacancy (NV) ensembles in diamond. T1
      was studied as a function of temperature from 5 to 475 K and magnetic field from
      0 to 630 G for several samples with various NV and nitrogen concentrations. Our
      studies reveal three processes responsible for T1 relaxation. Above room
      temperature, a two-phonon Raman process dominates; below room temperature, we
      observe an Orbach-type process with an activation energy of 73(4) meV, which
      closely matches the local vibrational modes of the NV center. At yet lower
      temperatures, sample dependent cross-relaxation processes dominate, resulting in
      temperature independent values of T1 from milliseconds to minutes. The value of
      T1 in this limit depends sensitively on the magnetic field and can be tuned by
      more than 1 order of magnitude.

PMID- 23003090
TI  - Nonadditivity of fluctuation-induced forces in fluidized granular media.
AB  - We investigate the effective long-range interactions between intruder particles
      immersed in a randomly driven granular fluid. The effective Casimir-like force
      between two intruders, induced by the fluctuations of the hydrodynamic fields,
      can change its sign when varying the control parameters: the volume fraction, the
      distance between the intruders, and the restitution coefficient. More
      interestingly, by inserting more intruders, we verify that the fluctuation
      induced interaction is not pairwise additive. The simulation results are
      qualitatively consistent with the theoretical predictions based on mode coupling
      calculations. These results shed new light on the underlying mechanisms of
      collective behaviors in fluidized granular media.

PMID- 23003092
TI  - Stripe formation in bacterial systems with density-suppressed motility.
AB  - Engineered bacteria in which motility is reduced by local cell density generate
      periodic stripes of high and low density when spotted on agar plates. We study
      theoretically the origin and mechanism of this process in a kinetic model that
      includes growth and density-suppressed motility of the cells. The spreading of a
      region of immotile cells into an initially cell-free region is analyzed. From the
      calculated front profile we provide an analytic ansatz to determine the phase
      boundary between the stripe and the no-stripe phases. The influence of various
      parameters on the phase boundary is discussed.

PMID- 23003091
TI  - Scaling of traction forces with the size of cohesive cell colonies.
AB  - To understand how the mechanical properties of tissues emerge from interactions
      of multiple cells, we measure traction stresses of cohesive colonies of 1-27
      cells adherent to soft substrates. We find that traction stresses are generally
      localized at the periphery of the colony and the total traction force scales with
      the colony radius. For large colony sizes, the scaling appears to approach
      linear, suggesting the emergence of an apparent surface tension of the order of
      10(-3)  N/m. A simple model of the cell colony as a contractile elastic medium
      coupled to the substrate captures the spatial distribution of traction forces and
      the scaling of traction forces with the colony size.

PMID- 23003093
TI  - Propagation of 2D pressure pulses in lipid monolayers and its possible
      implications for biology.
AB  - The existence and propagation of acoustic pressure pulses on lipid monolayers at
      the air-water interface are directly observed by simple mechanical detection. The
      pulses are excited by small amounts of solvents added to the monolayer.
      Controlling the state of the lipid interface, we show that the pulses propagate
      at velocities c following the lateral compressibility kappa. This is manifested
      by a pronounced minimum in c (~0.3  m/s) within the transition regime. The role
      of interface density pulses in biology is discussed, in particular, in the
      context of communicating localized alterations in protein function (signaling)
      and nerve pulse propagation.

PMID- 23003094
TI  - Vibration-induced liquefaction of granular suspensions.
AB  - We investigate the mechanical behavior of granular suspensions subjected to
      coupled vibrations and shear. At high shear stress, whatever the mechanical
      vibration energy and bead size, the system behaves like a homogeneous suspension
      of hard spheres. At low shear stress, in addition to a dependence on bead size,
      vibration energy drastically influences the viscosity of the material that can
      decrease by more than 2 orders of magnitude. All experiments can be rationalized
      by introducing a hydrodynamical Peclet number defined as the ratio between the
      lubrication stress induced by vibrations and granular pressure. The behavior of
      vibrated wet and dry granular materials can then be unified by assimilating the
      hookean stress in dry media to the lubrication stress in suspensions.

PMID- 23003095
TI  - Bubble production mechanism in a microfluidic foam generator.
AB  - We present the design and characterization of a microfluidic bubble generator
      that has the potential of producing monodisperse bubbles in 256 production
      channels that can operate in parallel. For a single production channel we
      demonstrate a production rate of up to 4 kHz with a coefficient of variation of
      less than 1%. We observe a two-stage bubble production mechanism: initially the
      gas spreads onto a shallow terrace, and then overflows into a larger foam
      collection channel; pinning of the liquid-gas meniscus is observed at the terrace
      edge, the result being an asymmetric pinch-off. A semiempirical physical model
      predicts the scaling of bubble size with fluid viscosity and gas pressure from
      measurements of the pinned meniscus width.

PMID- 23003096
TI  - Solutal convection in confined geometries: enhancement of colloidal transport.
AB  - We evidence experimentally and theoretically that natural convection driven by
      solutal density differences in a molecular binary mixture can boost the transport
      of colloids. We demonstrate that such buoyancy-driven flows have a negligible
      influence on the gradients that generate them, for moderate Rayleigh numbers in a
      confined geometry. These flows therefore do not homogenize the binary mixture but
      can disperse very efficiently large solutes. We illustrate the relevance of such
      effects thanks to several original experiments: drying of confined droplets,
      microfluidic evaporation, and interdiffusion in microfluidic flows.

PMID- 23003097
TI  - Optimal filling of shapes.
AB  - We present filling as a type of spatial subdivision problem similar to covering
      and packing. Filling addresses the optimal placement of overlapping objects lying
      entirely inside an arbitrary shape so as to cover the most interior volume. In n
      dimensional space, if the objects are polydisperse n-balls, we show that
      solutions correspond to sets of maximal n-balls. For polygons, we provide a
      heuristic for finding solutions of maximal disks. We consider the properties of
      ideal distributions of N disks as N->infinity. We note an analogy with energy
      landscapes.

PMID- 23003098
TI  - Comment on "Are there traps in quantum control landscapes?".

PMID- 23003100
TI  - Comment on "Effect of current sheets on the solar wind magnetic field power
      spectrum from the ulysses observation: from Kraichnan to Kolmogorov scaling".

PMID- 23003102
TI  - A mutational mimic analysis of histone H3 post-translational modifications:
      specific sites influence the conformational state of H3/H4, causing either
      positive or negative supercoiling of DNA.
AB  - Histone H3 has specific sites of post-translational modifications that serve as
      epigenetic signals to cellular machinery to direct various processes. Mutational
      mimics of these modifications (glutamine for acetylation, methionine and leucine
      for methylation, and glutamic acid for phosphorylation) were constructed at the
      relevant sites of the major histone variant, H3.2, and their effects on the
      conformational equilibrium of the H3/H4 tetramer at physiological ionic strength
      were determined when bound to or free of DNA. The deposition vehicle used for
      this analysis was NAP1, nucleosome assembly protein 1. Acetylation mimics in the
      N-terminus preferentially stabilized the left-handed conformer (DNA negatively
      supercoiled), and mutations within the globular region preferred the right-handed
      conformer (DNA positively supercoiled). The methylation mimics in the N-terminus
      tended to maintain characteristics similar to those of wild-type H3/H4; i.e., the
      conformational equilibrium maintains similar levels of both left- and right
      handed conformers. Phosphorylation mimics facilitated a mixed effect, i.e., when
      at serines, the left-handed conformer, and at threonines, a mixture of both
      conformers. When double mutations were present, the conformational equilibrium
      was shifted dramatically, either leftward or rightward depending on the specific
      sites. In contrast, these mutations tended not to affect the direction and extent
      of supercoiling for variants H3.1 and H3.3. Variant H3.3 promoted only the left
      handed conformer, and H3.1 tended to maintain both conformers. Additional
      experiments indicate the importance of a propagation mechanism for ensuring the
      formation of a particular superhelical state over an extended region of the DNA.
      The potential relevance of these results to the maintenance of epigenetic
      information on a gene is discussed.

PMID- 23003103
TI  - A nationwide evidence-based study of factors associated with hospitalisations due
      to unintentional poisoning and poisoning mortality in Taiwan.
AB  - The aim of this study was to explore the epidemiologic characteristics of
      unintentional poisoning cases and the factors associated with inpatient
      mortality. Data were retrieved from the National Health Insurance database from
      2005 to 2007. Patients with diagnosis classifications of ICD-9-CM E850-E869
      (unintentional poisoning) were selected. SPSS 18.0 software was used for the
      analysis. In Taiwan between 2005 and 2007, a total of 11,523 patients were
      hospitalised due to unintentional poisoning, with a hospitalisation rate of 16.83
      per 100,000, of which 60.1% and 39.9% were attributable to drug poisoning and
      solid, liquid and gas substance poisoning, respectively. The hospitalisation rate
      in men was higher than that of women. The age group of 45-64 had the highest
      hospitalisation rate of 52.85 per 100,000. The inpatient mortality rate increased
      with the presence of the following factors: age of 65 or older, surgery or
      procedure, a higher Charlson Comorbidity Index (CCI), short length of hospital
      stays, acute respiratory failure, alcohol poisoning, pesticide poisoning and a
      higher-level hospital visited. Methanol, herbicides and organophosphorus
      pesticide intoxications are associated with higher mortality rates. Therefore,
      when caring for patients poisoned by the above agents, healthcare professionals
      should look out for their clinical development to ensure quality of care and to
      reduce mortality. 

PMID- 23003104
TI  - Plant uptake of pharmaceutical chemicals detected in recycled organic manure and
      reclaimed wastewater.
AB  - Land application of recycled manure produced from biosolids and reclaimed
      wastewater can transfer pharmaceutical chemicals to terrestrial environments,
      giving rise to potential accumulation of these residues in edible plants. In this
      study, the potential for plant uptake of 13 pharmaceutical chemicals, and the
      relation between the accumulation features within the plant and the
      physicochemical properties were examined by exposing pea and cucumber to an
      aqueous solution containing pharmaceutical chemicals. Ten of 13 compounds tested
      were detected in plant leaves and stems. Comparison of the plant uptake
      characteristics and the octanol-water partition coefficient of pharmaceutical
      chemicals showed that compounds with an intermediate polarity such as
      carbamazepine and crotamiton could be easily transported to plant shoots.
      Moreover, these results suggest the possibility of highly hydrophilic
      pharmaceutical chemicals such as trimethoprim and sulfonamides to be accumulated
      in plant roots owing to their low permeability in root cell membranes.

PMID- 23003105
TI  - Transporter targeted gatifloxacin prodrugs: synthesis, permeability, and topical
      ocular delivery.
AB  - In this work, we aim to design and synthesize prodrugs of gatifloxacin targeting
      organic cation transporter (OCT), monocarboxylate transporter (MCT), and ATB (0,
      +) transporters and to identify a prodrug with enhanced delivery to the back of
      the eye. Dimethylamino-propyl, carboxy-propyl, and amino-propyl(2-methyl)
      derivatives of gatifloxacin (GFX), DMAP-GFX, CP-GFX, and APM-GFX, were designed
      and synthesized to target OCT, MCT, and ATB (0, +) transporters, respectively. An
      LC-MS method was developed to analyze drug and prodrug levels in various studies.
      Solubility and log D (pH 7.4) were measured for prodrugs and the parent drug. The
      permeability of the prodrugs was determined in the cornea, conjunctiva, and
      sclera-choroid-retinal pigment epitheluim (SCRPE) and compared with gatifloxacin
      using an Ussing chamber assembly. Permeability mechanisms were elucidated by
      determining the transport in the presence of transporter specific inhibitors. 1
      Methyl-4-phenylpyridinium iodide (MPP+), nicotinic acid sodium salt, and alpha
      methyl-DL-tryptophan were used to inhibit OCT, MCT, and ATB (0, +) transporters,
      respectively. A prodrug selected based on in vitro studies was administered as an
      eye drop to pigmented rabbits, and the delivery to various eye tissues including
      vitreous humor was compared with gatifloxacin dosing. DMAP-GFX exhibited 12.8
      fold greater solubility than GFX. All prodrugs were more lipophilic, with the
      measured log D (pH 7.4) values ranging from 0.05 to 1.04, when compared to GFX
      (log D: -1.15). DMAP-GFX showed 1.4-, 1.8-, and 1.9-fold improvement in
      permeability across the cornea, conjunctiva, and SCRPE when compared to GFX.
      Moreover, it exhibited reduced permeability in the presence of MPP+ (competitive
      inhibitor of OCT), indicating OCT-mediated transport. CP-GFX showed 1.2-, 2.3-,
      and 2.5-fold improvement in permeability across the cornea, conjunctiva, and
      SCRPE, respectively. In the presence of nicotinic acid (competitive inhibitor of
      MCT), the permeability of CP-GFX was reduced across the conjunctiva. However, the
      cornea and SCRPE permeability of CP-GFX was not affected by nicotinic acid. APM
      GFX did not show any improvement in permeability when compared to GFX across the
      cornea, conjunctiva, and SCRPE. Based on solubility and permeability, DMAP-GFX
      was selected for in vivo studies. DMAP-GFX showed 3.6- and 1.95-fold higher
      levels in vitreous humor and CRPE compared to that of GFX at 1 h after topical
      dosing. In vivo conversion of DMAP-GFX prodrug to GFX was quantified in tissues
      isolated at 1 h after dosing. The parent drug-to-prodrug ratio was 8, 70, 24, 21,
      29, 13, 55, and 60% in the cornea, conjunctiva, iris-ciliary body, aqueous humor,
      sclera, CRPE, retina, and vitreous humor, respectively. In conclusion, DMAP-GFX
      prodrug enhanced solubility, log D, as well as OCT mediated delivery of
      gatifloxacin to the back of the eye.

PMID- 23003106
TI  - The impact of calcineurin inhibitors on insulin sensitivity and insulin
      secretion: a randomized crossover trial in uraemic patients.
AB  - AIMS: The calcineurin inhibitors cyclosporine and tacrolimus are implicated in
      post-transplant complications such as new-onset diabetes after transplantation.
      The relative contribution of each calcineurin inhibitor to new-onset diabetes
      after transplantation remains unclear. We sought to compare the impact of
      cyclosporine and tacrolimus on glucose metabolism in humans. METHODS: Eight
      haemodialysis patients received 8-10 days of oral treatment followed by 5-h
      infusions with cyclosporine, tacrolimus and saline in a randomized, investigator
      blind, crossover study. Glucose metabolism and beta-cell function was
      investigated through: a hyperinsulinaemic-euglycaemic clamp, an intravenous
      glucose tolerance test and insulin concentration time series. RESULTS:
      Cyclosporine and tacrolimus decreased insulin sensitivity by 22% (P = 0.02) and
      13% (P = 0.048), respectively. The acute insulin response and pulsatile insulin
      secretion were not significantly affected by the drugs. CONCLUSION: In
      conclusion, 8-10 days of treatment with cyclosporine and tacrolimus impairs
      insulin sensitivity to a similar degree in haemodialysis patients, while acute
      insulin responses and pulsatile insulin secretion remain unaffected.

PMID- 23003107
TI  - Potential contaminant pathways from hydraulically fractured shale aquifers.

PMID- 23003108
TI  - One-dimensional uranyl-2,2'-bipyridine coordination polymer with cation-cation
      interactions: (UO2)2(2,2'-bpy)(CH3CO2)(O)(OH).
AB  - A uranyl-2,2'-bipyridine coordination polymer, (UO(2))(2)(2,2'
      bpy)(CH(3)CO(2))(O)(OH) (1; 2,2'-bpy = 2,2'-bipyridine) has been synthesized
      hydrothermally at 165  degrees C and characterized via single-crystal X-ray
      diffraction and UV-vis-near-IR, fluorescence, and IR spectroscopies. The
      structure consists of two uranyl pentagonal bipyramids that are linked through
      cation-cation interactions (CCIs) to form chains that are truncated in the second
      and third dimensions by 2,2'-bpy. These chains of uranyl polyhedra consist of a
      rare case of CCIs through the edge-sharing polyhedral connection mode instead of
      the more common corner-sharing connection mode. 1 is the first uranium(VI)
      compound reported that contains CCIs in which the structural unit is one
      dimensional, although lower-dimensional structural units with CCIs are known for
      pentavalent actinides.

PMID- 23003109
TI  - Synthesis of phenol derivatives from cyclohex-2-enones bearing an alkyne through
      Lewis acid-catalyzed enolization and intramolecular Alder-Rickert reaction.
AB  - A cationic rhodium(I) complex- or In(OTf)(3)-catalyzed synthesis of phenol
      derivatives from cyclohex-2-enone having an ethoxycarbonyl-substituted alkyne has
      been achieved. This reaction proceeds via enolization and an intramolecular Alder
      Rickert reaction.

PMID- 23003110
TI  - Plasmakinetic bipolar versus monopolar transurethral resection of non-muscle
      invasive bladder cancer: a single center randomized controlled trial.
AB  - OBJECTIVES: To compare the safety and the efficacy of plasmakinetic bipolar
      resectoscope versus conventional monopolar in the transurethral resection of
      primary non-muscle invasive bladder cancer. METHODS: From January 2007 to
      December 2009, 132 patients underwent endoscopic resection for primary non-muscle
      invasive bladder cancer. They were randomly assigned to two groups: 67 patients
      underwent a transurethral resection of the bladder with bipolar plasmakinetic
      energy transurethral resection of the bladder and 65 were treated with
      conventional monopolar transurethral resection. RESULTS: The mean operative time
      was 27 min for bipolar plasmakinetic energy transurethral resection of the
      bladder and 31 min for monopolar transurethral resection of the bladder. No
      significant differences in the mean change of hemoglobin and serum sodium level
      were observed. Mean catheterization time was 1.3 days and 2.3 days for bipolar
      plasmakinetic energy transurethral resection of the bladder and monopolar
      transurethral resection of the bladder, respectively. The mean hospital stay was
      shorter in the bipolar plasmakinetic energy transurethral resection of the
      bladder. Bladder perforation was reported in two cases for the monopolar
      transurethral resection of the bladder group and obturator nerve reflex occurred
      in a single case for both procedures. None of the patients experienced
      transurethral resection syndrome. The median time of bladder tumor recurrence
      after initial transurethral resection of the bladder was 12.4 months and 11.9
      months for bipolar plasmakinetic energy transurethral resection of the bladder
      and monopolar transurethral resection of the bladder, respectively. No
      significant differences in the overall recurrence-free survival rate were
      observed comparing the two procedures. CONCLUSIONS: Plasmakinetic bipolar
      transurethral resection represents a safe and effective procedure in the
      management of non-muscle invasive bladder cancer.

PMID- 23003111
TI  - Immunogenic characterization of outer membrane porins OmpC and OmpF of porcine
      extraintestinal pathogenic Escherichia coli.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) is an important pathogen that
      can cause systemic infections in a broad spectrum of mammals and birds. To date,
      commercial vaccines against ExPEC infections in pigs are rare and antibiotic
      resistance has become a serious clinical problem. Identification of protective
      antigens is helpful for developing potentially effective vaccines. In this study,
      two outer membrane porins, OmpC and OmpF, of porcine ExPEC were cloned and
      expressed to investigate their immunogenicity. Intraperitoneal immunization of
      mice with the purified recombinant proteins OmpC and OmpF stimulated strong
      immunoglobulin G (IgG) antibody responses. Both IgG1 and IgG2a subclasses were
      induced, with a predominance of IgG1 production. After challenge with 2.5 * 10(7)
      CFU (5 * LD50 ) of the highly virulent ExPEC strain PCN033, 62.5% and 87.5%
      protection was observed in mice immunized with OmpC and OmpF, respectively. In
      addition, both anti-OmpC and anti-OmpF sera can mediate complement-dependent
      opsonophagocytosis. Phylogenetic analysis showed that the ompC gene was
      ubiquitously present in all E. coli strains, whereas the ompF gene was mutated in
      certain strains. Furthermore, the selection analysis indicated that gene ompC may
      be subject to strong immune pressure. Our results demonstrated that OmpC is a
      promising vaccine target against ExPEC infections in swine.

PMID- 23003112
TI  - Medical abortion service in rural areas of Henan Province, China: a provider
      survey.
AB  - AIM: The aim of this study was to explore the knowledge, attitudes and practices
      on medical abortion of abortion service providers in rural areas of China.
      MATERIAL AND METHODS: A cross-sectional study via self-administered questionnaire
      was conducted among 362 abortion service providers from family planning service
      centers (FPSC) and hospitals in rural areas of Henan Province, China, between
      November 2009 and May 2010. RESULTS: Most of the providers were female (99.4%)
      and obstetricians/gynecologists (63.3%). The knowledge score achieved ranged from
      9.4 to 78.1 points, with both the median and the mode of 56.3 points. Of the
      52.2% (189/362) of providers having a preference on abortion method, 30.2%
      (57/189) preferred medical abortion, while 69.8% (132/189) preferred surgical
      abortion. In total, 50.7% (174/343) of the providers indicated the provision of
      medical abortion should be expanded, with the three biggest challenges in its
      further expansion being increased complications/failures, poor client
      knowledge/awareness, and problems with drug/equipment supplies. Of all the
      providers, 81.7% and 92.2% reported they had experience in providing medical
      abortion and surgical abortion, respectively. Medical abortion providers were
      mainly experienced in misoprostol with oral (81.8%)/vaginal (79.6%) prostaglandin
      (misoprostol/gemeprost). CONCLUSION: Knowledge on medical abortion of providers
      working in rural China was at a moderate level. Providers preferred surgical
      abortion to medical abortion. Providers have more experience in providing
      surgical abortion than medical abortion. Efforts should be made to overcome the
      perceived challenges in future expansion of medical abortion.

PMID- 23003113
TI  - Serum 25-hydroxyvitamin d levels and C-reactive protein in persons with human
      immunodeficiency virus infection.
AB  - Human immunodeficiency virus (HIV) infection has frequently been associated with
      vitamin D deficiency as well as chronic inflammatory response. We tested the
      hypothesis of an independent relationship between serum concentrations of 25
      hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (CRP) in a
      cohort of HIV-positive people. A cross-sectional survey was conducted among 316
      HIV-positive people (181 men and 135 women) aged 16 to 60 years residing in the
      Kathmandu Valley, Nepal. Serum high-sensitivity CRP concentrations and serum
      25(OH)D levels were measured by the latex agglutination nephelometry method and
      the competitive protein-binding assay, respectively. The relationship between
      serum CRP concentrations and 25(OH)D serum level was assessed using multiple
      logistic regression analysis with adjustment of potential cardiovascular and HIV
      related factors. The proportions of participants with 25(OH)D serum levels <20
      ng/ml, 20-30 ng/ml, and >=30 ng/ml were 83.2%, 15.5%, and 1.3%, respectively. The
      mean 25(OH)D serum levels in men and women were 15.3 ng/ml and 14.4 ng/ml,
      respectively. Participants with a 25(OH)D serum level of <20 ng/ml had a 3.2-fold
      higher odds of high CRP (>3 mg/liter) compared to those with a 25(OH)D serum
      level of >=20 ng/ml (p=0.005). Men and women with a 25(OH)D serum level of <20
      ng/ml had 3.2- and 2.7-fold higher odds of high CRP (>3 mg/liter), respectively,
      compared to those with a 25(OH)D serum level of >=20 ng/ml. The relationships
      remained significant only in men (p =0.02) but not in women (p=0.28). The risk of
      having a high level of inflammation (CRP>3 mg/liter) may be high among HIV
      positive men and women with a 25(OH)D serum level of <20 ng/ml.

PMID- 23003114
TI  - Intimate partner violence and substance use among Hawai'i youth: an analysis of
      recent data from the Hawai'i Youth Risk Behavior Survey.
AB  - OBJECTIVE: This study explored the relationship between adolescent substance use
      and intimate partner violence (IPV). METHOD: A secondary data analysis was
      conducted using the statewide Hawai'i Youth Risk Behavior Survey data for the
      years 2005, 2007, and 2009. Public school students (n = 4,364) attending medium
      to large school districts in Hawai'i participated. Prevalence estimates and
      regression models of covariates were calculated. RESULTS: Results indicated that
      IPV victimization and substance use are prevalent among Hawai'i youth. Odds ratio
      calculations indicated that substance use (specifically multiple drug use) is
      associated with an increased likelihood of reporting IPV victimization.
      CONCLUSIONS: Curricula and programming to prevent drug use among Hawai'i youth
      must incorporate IPV prevention, and vice versa.

PMID- 23003115
TI  - Cognitive behavioral therapy for depression in older people: a meta-analysis and
      meta-regression of randomized controlled trials.
AB  - OBJECTIVES: To review the effectiveness of cognitive behavioral therapy (CBT) for
      depression in older people, together with factors associated with its efficacy.
      DESIGN: Online literature databases and registers were searched for randomized
      controlled trials (RCTs) of CBT for depression in older people. Random-effects
      meta-analysis and meta-regression were conducted. SETTING: Studies involving
      participants from the community and inpatient and outpatient clinical settings
      were included in the meta-analysis. PARTICIPANTS: Older people with major or
      minor depression, dysthymia, or depressive symptoms. MEASUREMENTS: Evidence-based
      outcome measures of depression. RESULTS: Four hundred eighty-five studies were
      identified, of which 23 were included. At the end of the intervention, CBT was
      significantly more effective at reducing depressive symptoms (irrespective of
      whether rated by clinicians or participants) than treatment as usual (TAU) or
      being on a waiting list but not than active controls. The same pattern of results
      was found for 6-month follow-up. At all other time-points, pooled effect sizes in
      favor of CBT were nonsignificant. Clinician-rated outcome measures resulted in
      larger effect sizes in favor of CBT than self-rated measures. No significant
      differences in efficacy were found between CBT and other treatment
      (pharmacotherapy and other psychotherapies). Meta-regression analyses revealed
      four factors that predicted effect sizes for comparisons between CBT and control
      conditions, including whether concurrent pharmacotherapy was allowed. CONCLUSION:
      CBT for depression in older people is more effective than waiting list or TAU,
      but greater efficacy than active controls or other treatment has not been
      demonstrated. More high-quality RCTs comparing CBT with active controls need to
      be conducted before firm conclusions can be drawn about the efficacy of CBT for
      depression in older people. Other treatment approaches that could be contrasted
      with or augment CBT (e.g., pharmacotherapy) also need to be explored further.

PMID- 23003116
TI  - Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow
      up study.
AB  - OBJECTIVE: We investigated the risk of dementia in patients with type 2 diabetes
      with or without prior hypoglycaemic episodes. SUBJECTS AND SETTING: One million
      subjects randomly selected from the National Health Insurance Research Database,
      Taiwan. RESULTS: A total of 15 404 diabetic subjects without prior dementia and a
      mean age of 64.2 years were enrolled in the study. About 2% (n = 289) of
      participants had at least one episode of hypoglycaemia in a 3-year period; these
      subjects were older and more likely to be women and also had higher rates of
      insulin use and comorbidities compared to those without hypoglycaemia. During a
      total of 7 years of follow-up (mean and median follow-up, 3.8 and 4.8 years,
      respectively), 1106 patients with diabetes (7.2%) developed dementia. The
      incidence rate of dementia was higher in diabetic subjects with [29.9 per 1000
      person-years (95% CI 22.1-39.2)] compared to those without [11.1 per 1000 person
      years (95% CI 10.3-11.8)] hypoglycaemic episodes. The crude rate ratio (RR) and
      age- and gender-adjusted RR values for dementia were 2.76 (95% CI 2.06-3.70, P <
      0.001) and 1.60 (95% CI 1.19-2.14, P = 0.002), respectively, in diabetic subjects
      with hypoglycaemia compared to those without hypoglycaemia. Results of Cox
      proportional hazards analysis revealed that hypoglycaemia, older age, female
      gender and insulin use were independent predictors of dementia. CONCLUSION: Adult
      diabetic patients with prior hypoglycaemia had a significantly increased risk of
      dementia. The influence of hypoglycaemic episodes on brain function warrants
      further investigation.

PMID- 23003117
TI  - Standardized Beck Depression Inventory-II scores for male veterans coping with
      chronic pain.
AB  - The Beck Depression Inventory II (BDI-II) has been suspected of overestimating
      the level of depression in individuals that endure chronic pain. Using a sample
      (N = 345) of male military veterans with chronic pain enrolled in an outpatient
      treatment program, a factor analysis on the BDI-II revealed a "Somatic
      Complaints" factor along with 2 other factors we labeled "Negative Rumination"
      and "Mood." Standardized scores were provided for each BDI-II factor score, Total
      score, and Total minus Somatic score. The internal consistency reliabilities
      (Gilmer-Feldt and alpha coefficients) for all scores were found to be clinically
      acceptable. Item-Total score correlations found that all of the BDI-II items were
      good discriminators (r > .30). We conclude that the normative data provided in
      this study should help control for somatic responding by male chronic pain
      veterans on the BDI-II. We highly recommend that clinicians and researchers use
      the norm-referenced method when interpreting BDI-II scores from individuals
      suffering from chronic pain.

PMID- 23003118
TI  - Hematologic and plasma biochemical reference intervals for health monitoring of
      wild Australian tree frogs.
AB  - BACKGROUND: Few hematologic and biochemical reference intervals for wild
      amphibians have been established. Reference values would aid in early detection
      of emerging infectious diseases, which are a significant problem for amphibian
      conservation efforts. OBJECTIVE: We aimed to establish reference intervals for a
      wide range of hematologic and plasma biochemistry variables for 2 species of
      Australian tree frogs, describe morphologic features of leukocytes, and analyze
      the effects of season, year, and parasite status on blood values. METHODS: Blood
      specimens were collected from reference populations of wild adult Australian tree
      frogs, Litoria caerulea and L infrafrenata, for analysis of hematologic (manual)
      variables, plasma biochemical (automated) analytes, and plasma and serum proteins
      using automated methods, refractometry, and electrophoresis. RESULTS: Inter- and
      intraspecies differences were found in L caerulea (n = 80) and L infrafrenata (n
      = 66) frogs for hematologic and biochemical variables. Intraspecies differences
      were largely associated with seasonal variations. In the dry season, both species
      had higher WBC counts, with higher lymphocyte counts in L caerulea and higher
      neutrophil counts in L infrafrenata, and uric acid concentrations. In the wet
      season, both species had higher glucose and potassium concentrations, L caerulea
      frogs had higher neutrophil counts, and L infrafrenata frogs had higher total
      protein, phosphorus, and sodium concentrations, AST activity, PCV, hemoglobin
      concentration, and RBC, thrombocyte, and basophil counts. Hemogregarines were
      identified in 19% of blood samples from L infrafrenata frogs; multiple
      hematologic and biochemical variables were altered in infected frogs.
      CONCLUSIONS: Wide interspecies and seasonal variations highlight the need to
      establish species- and season-specific reference intervals for amphibians.
      Hematologic and plasma biochemical reference values should be useful in assessing
      the health status and in detecting emerging diseases in wild amphibians.

PMID- 23003119
TI  - Enhanced hole injection in phosphorescent organic light-emitting diodes by
      thermally evaporating a thin indium trichloride layer.
AB  - An ultrathin layer of indium trichloride (InCl(3)) is thermally evaporated on the
      indium tin oxide (ITO) anode to enhance the hole injection in simplified
      phosphorescent organic light-emitting diodes (PHOLEDs). Comparing with the device
      with ultraviolet (UV)-ozone treatment, the device modified by InCl(3) exhibits a
      maximum current efficiency of 82.2 cd/A measured at about 2000 cd/cm(2) and 36%
      improvement in power efficiency measured at 20 mA/cm(2). More importantly, more
      than three times improvement in half lifetime estimated at an initial luminance
      of 1000 cd/cm(2) is achieved. The investigations using ultraviolet photoelectron
      spectroscopy, X-ray photoelectron spectroscopy, and the bias- and temperature
      dependent current density-voltage characteristics in the related hole-dominated
      devices have revealed that the improved device performance is mainly attributed
      to the enhanced hole injection resulting from the lowered hole injection barrier
      height in the InCl(3)-modified devices.

PMID- 23003120
TI  - The brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, and
      induced nitric oxide synthase expressions after low-level laser therapy in an
      axonotmesis experimental model.
AB  - BACKGROUND DATA: A robust body of evidence has shown that low-level laser therapy
      (LLLT) improves peripheral nerve regeneration. However, the biochemical
      background triggered in this process is not yet fully understood. OBJECTIVE: The
      purpose of this study was to evaluate the mRNA expression of neurotrophic factors
      (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and
      neurotrophin-3, [NT-3]) and also an inflammatory marker (induced nitric oxide
      synthase [iNOS]) in an axonotmesis experimental model after low-level laser
      therapy. METHODS: Thirty-six adult male Wistar rats (250-350 g) were subjected to
      right sciatic nerve crush injury, and 24 h later, the animals in the three
      different experimental groups (n=18) were irradiated on a daily basis with helium
      neon laser (collimated HeNe laser, continuous emission, wavelength: 632.8 nm,
      power density: 0.5 mW/cm(2), irradiation time: 20 sec, energy density: 10
      J/cm(2)) during 7, 14, and 21 consecutive days, respectively. The control group
      (n=18) underwent the same procedures, but with the equipment turned off. At the
      end of the experiments, animals were killed with an overdose of anesthesia to
      remove samples from the sciatic nerve lesion epicenter to determine the mRNA
      expression of BDNF, NGF, NT-3 and iNOS enzyme. RESULTS: Comparisons between
      groups showed that HeNe laser increased the mRNA expression of both BDNF and NGF
      factors after 14 days of LLLT, with peak expression at the 21st day. Increase in
      NT-3 mRNA expression was not observed. In addition, HeNe laser produced iNOS
      expression reduction, which played an important role in the inflammatory process.
      CONCLUSIONS: The reported data could have a relevant practical value because LLLT
      is a noninvasive procedure, and have revealed significant increase in
      neurotrophic factor expressions and inflammatory process reduction, opening the
      possibility of using LLLT as an important aid to nerve regeneration process.

PMID- 23003121
TI  - Effects of 405 nm diode laser on titanium oxide bleaching activation.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of a 405 nm
      diode laser on bleaching reaction of H(2)O(2) and VL-TiO(2) on methylene blue
      (MB) dye. BACKGROUND DATA: Visible light activating titanium dioxide
      photocatalyst (VL-TiO(2)) may improve efficacy of hydrogen peroxide (H(2)O(2))
      bleaching agents used in dentistry while contributing to their safety by lowering
      the required concentration of peroxide. METHODS: The experimental solution was
      prepared with H(2)O(2), VL-TiO(2), MB, and pure water. The final concentration of
      H(2)O(2) was 3.5% and that of MB was 10 ppm. The experimental solution of 3 mL in
      a quartz cell was irradiated by a 405 nm diode laser with various powers, duty
      cycles, and pulse durations for 7 min. RESULTS: In all irradiation conditions,
      the increase in laser irradiation time gradually decreased the MB concentration.
      Irradiation by higher output power showed more reduction of MB concentration.
      Pulse durations as short as 5 ms with duty cycle reduced to 25% did not affect
      the degree of the reduction in MB concentration compared with continuous wave
      irradiation at the same average output power. CONCLUSIONS: It was concluded that
      using 405 nm diode laser, the bleaching effects of VL-TiO(2) depended upon the
      irradiation time and the average output power, regardless of pulse duration or
      duty cycle.

PMID- 23003122
TI  - Bactericidal effects of Nd:YAG laser irradiation and sodium hypochlorite solution
      on Enterococcus faecalis biofilm.
AB  - OBJECTIVE: The aim of this study was to evaluate the bactericidal effects of
      Nd:YAG laser on biofilm of Enterococcus faecalis. BACKGROUND DATA: It is
      difficult to eliminate bacterial biofilms with routine endodontic preparation
      techniques. It might be possible to eliminate biofilms remaining in the root
      canals of teeth with lasers. MATERIALS AND METHODS: The root canals of 60
      extracted teeth were prepared and E. faecalis biofilms were formed within the
      root canals. Then the teeth were randomly divided into four groups of 15. Group 1
      samples did not undergo any interventions, to serve as controls. Group 2 samples
      underwent a 3-W laser beam for 10 sec. The root canals in group 3 were irrigated
      with 1% sodium hypochlorite for 15 min and then irradiated with a 3-W laser beam
      for 10 sec. The root canals in group 4 were irrigated with 1% sodium hypochlorite
      for 15 min. Dentin chips were collected from the root canal walls and weighed.
      Then the chips were used to prepare a suspension. The classic colony-forming unit
      (CFU) counting technique was used to determine remaining bacterial counts.
      RESULTS: The bacterial counts in groups 2 and 4 had decreased to 54% and 2.39% of
      the control group, respectively. In group 3 no bacterial growth was observed.
      There were no significant differences between groups 1 and 2 (p>0.05).
      CONCLUSIONS: Based on the results of the present study, the effect of Nd:YAG
      laser beam on E. faecalis biofilm is less than that of sodium hypochlorite
      solution. A combination of laser and sodium hypochlorite results in complete
      elimination of E. faecalis biofilm.

PMID- 23003123
TI  - Photodynamic therapy (PDT) may provide effective palliation in the treatment of
      primary tracheal carcinoma: a small case series.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of photodynamic
      therapy (PDT) in primary tracheal carcinomas. METHODS: Data were obtained from
      patients treated with Photofrin((r)) PDT for primary tracheal carcinoma at the
      Ohio State University. Demographic data as well as survival and response were
      collected. RESULTS: Ten patients 47-79 years of age with primary tracheal
      carcinoma (three adenoid cystic, seven squamous histology) were treated with PDT.
      Treatment was part of curative-intent therapy in three patients, one of whom
      underwent surgery. The other seven patients received palliative PDT. Five
      patients received sequential radiation and two received concurrent chemotherapy.
      All 10 patients had improvement in obstructive symptoms within 1 month. Eight
      patients had objective response by bronchoscopy, and one patient had stable
      disease. Treatment was well tolerated. One patient developed a tracheal stricture
      that was successfully treated with stent placement. CONCLUSIONS: PDT is safe and
      provides effective palliation of obstructive symptoms in patients with primary
      tracheal carcinoma. PDT has a potential role in both the curative and the
      palliative setting.

PMID- 23003124
TI  - Diurnal blood pressure variations are associated with changes in distal-proximal
      skin temperature gradient.
AB  - It is generally assumed that skin vascular resistance contributes only to a small
      extent to total peripheral resistance and hence to blood pressure (BP). However,
      little is known about the impact of skin blood flow (SBF) changes on the diurnal
      variations of BP under ambulatory conditions. The main aim of the study was to
      determine whether diurnal patterns of distal SBF are related to mean arterial BP
      (MAP). Twenty-four-hour ambulatory measurements of BP, heart rate (HR) and distal
      (mean of hands and feet) as well as proximal (mean of sternum and infraclavicular
      region) skin temperatures were carried out in 51 patients (men/women = 18/33)
      during a 2-d eye hospital investigation. The standardized ambulatory protocol
      allowed measurements with minimal interference from uncontrolled parameters and,
      hence, some conclusive interpretations. The distal minus proximal skin
      temperature gradient (DPG) provided a measure for distal SBF. Individual cross
      correlation analyses revealed that the diurnal pattern of MAP was nearly a mirror
      image of DPG and hence of distal SBF. Scheduled lunch and dinner induced an
      increase in DPG and a decline in MAP, while HR increased. Low daytime DPG (i.e.
      low distal SBF) levels significantly predicted sleep-induced BP dipping (r = 
      .436, p = .0014). Preliminary path analysis suggested that outdoor air
      temperature and atmospheric pressure may act on MAP via changed distal SBF.
      Changes in distal SBF may contribute to diurnal variation in MAP, including sleep
      induced BP dipping and changes related to food intake. This finding might have an
      impact on individual cardiovascular risk prediction with respect to diurnal,
      seasonal and weather variations; however, the underlying mechanisms remain to be
      discovered.

PMID- 23003125
TI  - Prevalence and clinical significance of low-avidity HPA-1a antibodies in women
      exposed to HPA-1a during pregnancy.
AB  - BACKGROUND: Recent studies suggest that HPA-1a-specific, low-avidity maternal
      antibodies not detectable by conventional methods can cause neonatal alloimmune
      thrombocytopenia (NAIT). We performed studies to further define the incidence and
      clinical significance of this type of antibody. STUDY DESIGN AND METHODS: Surface
      plasmon resonance analysis was used to detect low-avidity antibodies in HPA-1a
      negative, "antibody-negative" mothers of suspected NAIT cases. The ability of
      antibodies detected to promote immune destruction of human platelets (PLTs) was
      examined in a newly developed NOD/SCID mouse model. RESULTS: Among 3478 suspected
      cases of NAIT, 677 HPA-1a-negative mothers were identified. HPA-1a-specific
      antibodies were detected by conventional antibody testing in 616 cases (91%). Low
      avidity HPA-1a-specific antibodies were identified in 18 of the remaining 61
      cases (9%). Clinical follow-up on 13 cases showed that eight were referred
      because of suspected NAIT and five because the mother's sister had previously had
      an infant with NAIT. Only six infants born to the 13 sensitized mothers had
      clinically significant thrombocytopenia at birth. Three of four low-avidity
      antibodies tested in the mouse caused accelerated clearance of HPA-1a/a but not
      HPA-1b/b PLTs. Only 3 of 12 mothers with low-avidity HPA-1a antibodies were
      positive for HLA-DRB3*0101. CONCLUSIONS: The findings confirm previous reports
      that low-avidity HPA-1a antibodies can cause NAIT but show that the presence of
      such an antibody does not predict that an infant will be affected. The low
      incidence of HLA-DRB3*0101 in this cohort (p < 0.0001) suggests that women
      negative for DRB3*0101 may be predisposed to produce low-avidity HPA-1a
      antibodies.

PMID- 23003127
TI  - All entangled quantum states are nonlocal.
AB  - Departing from the usual paradigm of local operations and classical communication
      adopted in entanglement theory, we study here the interconversion of quantum
      states by means of local operations and shared randomness. A set of necessary and
      sufficient conditions for the existence of such a transformation between two
      given quantum states is given in terms of the payoff they yield in a suitable
      class of nonlocal games. It is shown that, as a consequence of our result, such a
      class of nonlocal games is able to witness quantum entanglement, however weak,
      and reveal nonlocality in any entangled quantum state. An example illustrating
      this fact is provided.

PMID- 23003128
TI  - Tuning a spin bath through the quantum-classical transition.
AB  - We study decoherence of a single nitrogen-vacancy (NV) center induced by the 13C
      nuclear spin bath of diamond. By comparing Hahn-Echo experiments on single and
      double-quantum transitions of the NV triplet ground state we demonstrate that
      this bath can be tuned into two different regimes. At low magnetic fields, the
      nuclei behave as a quantum bath which causes decoherence by entangling with the
      NV central spin. At high magnetic fields, the bath behaves as a source of
      classical magnetic field noise, which creates decoherence by imprinting a random
      phase on the NV central spin.

PMID- 23003129
TI  - Time asymmetry of probabilities versus relativistic causal structure: an arrow of
      time.
AB  - There is an incompatibility between the symmetries of causal structure in
      relativity theory and the signaling abilities of probabilistic devices with
      inputs and outputs: while time reversal in relativity will not introduce the
      ability to signal between spacelike separated regions, this is not the case for
      probabilistic devices with spacelike separated input-output pairs. We explicitly
      describe a nonsignaling device which becomes a perfect signaling device under
      time reversal, where time reversal can be conceptualized as playing backwards a
      videotape of an agent manipulating the device. This leads to an arrow of time
      that is identifiable when studying the correlations of events for spacelike
      separated regions. Somewhat surprisingly, although the time reversal of Popescu
      Rohrlich boxes also allows agents to signal, it does not yield a perfect
      signaling device. Finally, we realize time reversal using postselection, which
      could to lead experimental implementation.

PMID- 23003130
TI  - Solving condensed-matter ground-state problems by semidefinite relaxations.
AB  - We present a generic approach to the condensed-matter ground-state problem which
      is complementary to variational techniques and works directly in the
      thermodynamic limit. Relaxing the ground-state problem, we obtain semidefinite
      programs (SDP). These can be solved efficiently, yielding strict lower bounds to
      the ground-state energy and approximations to the few-particle Green's functions.
      As the method is applicable for all particle statistics, it represents, in
      particular, a novel route for the study of strongly correlated fermionic and
      frustrated spin systems in D>1 spatial dimensions. It is demonstrated for the XXZ
      model and the Hubbard model of spinless fermions. The results are compared
      against exact solutions, quantum Monte Carlo calculations, and Anderson bounds,
      showing the competitiveness of the SDP method.

PMID- 23003131
TI  - Experimental fully contextual correlations.
AB  - Quantum correlations are contextual yet, in general, nothing prevents the
      existence of even more contextual correlations. We identify and test a
      noncontextuality inequality in which the quantum violation cannot be improved by
      any hypothetical postquantum theory, and use it to experimentally obtain
      correlations in which the fraction of noncontextual correlations is less than
      0.06. Our correlations are experimentally generated from the results of
      sequential compatible tests on a four-state quantum system encoded in the
      polarization and path of a single photon.

PMID- 23003132
TI  - One-shot classical-quantum capacity and hypothesis testing.
AB  - The one-shot classical capacity of a quantum channel quantifies the amount of
      classical information that can be transmitted through a single use of the channel
      such that the error probability is below a certain threshold. In this work, we
      show that this capacity is well approximated by a relative-entropy-type measure
      defined via hypothesis testing. Combined with a quantum version of Stein's lemma,
      our results give a conceptually simple proof of the well-known Holevo-Schumacher
      Westmoreland theorem for the capacity of memoryless channels. More generally, we
      obtain tight capacity formulas for arbitrary (not necessarily memoryless)
      channels.

PMID- 23003133
TI  - Blind quantum computing with weak coherent pulses.
AB  - The universal blind quantum computation (UBQC) protocol [A. Broadbent, J.
      Fitzsimons, and E. Kashefi, in Proceedings of the 50th Annual IEEE Symposiumon
      Foundations of Computer Science (IEEE Computer Society, Los Alamitos, CA, USA,
      2009), pp. 517-526.] allows a client to perform quantum computation on a remote
      server. In an ideal setting, perfect privacy is guaranteed if the client is
      capable of producing specific, randomly chosen single qubit states. While from a
      theoretical point of view, this may constitute the lowest possible quantum
      requirement, from a pragmatic point of view, generation of such states to be sent
      along long distances can never be achieved perfectly. We introduce the concept of
      epsilon blindness for UBQC, in analogy to the concept of epsilon security
      developed for other cryptographic protocols, allowing us to characterize the
      robustness and security properties of the protocol under possible imperfections.
      We also present a remote blind single qubit preparation protocol with weak
      coherent pulses for the client to prepare, in a delegated fashion, quantum states
      arbitrarily close to perfect random single qubit states. This allows us to
      efficiently achieve epsilon-blind UBQC for any epsilon>0, even if the channel
      between the client and the server is arbitrarily lossy.

PMID- 23003134
TI  - Number of relevant directions in principal component analysis and Wishart random
      matrices.
AB  - We compute analytically, for large N, the probability P(N+,N) that a N*N Wishart
      random matrix has N+ eigenvalues exceeding a threshold Nzeta, including its large
      deviation tails. This probability plays a benchmark role when performing the
      principal component analysis of a large empirical data set. We find that
      P(N+,N)~exp[-betaN2psizeta(N+/N)], where beta is the Dyson index of the ensemble
      and psizeta(kappa) is a rate function that we compute explicitly in the full
      range 0<=kappa<=1 and for any zeta. The rate function psizeta(kappa) displays a
      quadratic behavior modulated by a logarithmic singularity close to its minimum
      kappa?(zeta). This is shown to be a consequence of a phase transition in an
      associated Coulomb gas problem. The variance Delta(N) of the number of relevant
      components is also shown to grow universally (independent of zeta) as
      Delta(N)~(betapi2)-1 lnN for large N.

PMID- 23003135
TI  - Probing the equation of state of nuclear matter via neutron star
      asteroseismology.
AB  - We general-relativistically calculate the frequency of fundamental torsional
      oscillations of neutron star crusts, where we focus on the crystalline properties
      obtained from macroscopic nuclear models in a way that is dependent on the
      equation of state of nuclear matter. We find that the calculated frequency is
      sensitive to the density dependence of the symmetry energy, but almost
      independent of the incompressibility of symmetric nuclear matter. By identifying
      the lowest-frequency quasiperiodic oscillation in giant flares observed from soft
      gamma-ray repeaters as the fundamental torsional mode and allowing for the
      dependence of the calculated frequency on stellar models, we provide a lower
      limit of the density derivative of the symmetry energy as L?50  MeV.

PMID- 23003136
TI  - Absence of three-loop four-point ultraviolet divergences in N=4 supergravity.
AB  - We compute the coefficient of the potential three-loop four-point ultraviolet
      divergence in pure N=4 supergravity and show that it vanishes, contrary to
      expectations from symmetry arguments. The recently uncovered duality between
      color and kinematics is used to greatly streamline the calculation. We comment on
      all-loop cancellations hinting at further surprises awaiting discovery at higher
      loops.

PMID- 23003137
TI  - Final analysis and results of the Phase II SIMPLE dark matter search.
AB  - We report the final results of the Phase II SIMPLE measurements, comprising two
      run stages of 15 superheated droplet detectors each, with the second stage
      including an improved neutron shielding. The analyses include a refined signal
      analysis, and revised nucleation efficiency based on a reanalysis of previously
      reported monochromatic neutron irradiations. The combined results yield a contour
      minimum of sigmap=5.7*10(-3)  pb at 35  GeV/c2 in the spin-dependent sector of
      weakly interacting massive particle (WIMP) proton interactions, the most
      restrictive to date for MW}<=60  GeV/c2 from a direct search experiment and
      overlapping, for the first time, with results previously obtained only
      indirectly. In the spin-independent sector, a minimum of 4.7*10(-6)  pb at 35 
      GeV/c2 is achieved, with the exclusion contour challenging a significant part of
      the light mass WIMP region of current interest.

PMID- 23003139
TI  - Characteristics of thermalization of boost-invariant plasma from holography.
AB  - We report on the approach toward the hydrodynamic regime of boost-invariant N=4
      super Yang-Mills plasma at strong coupling starting from various far-from
      equilibrium states at tau=0. The results are obtained through a numerical
      solution of Einstein's equations for the dual geometries, as described in detail
      in the companion article [M. P. Heller, R. A. Janik, and P. Witaszczyk,
      arXiv:1203.0755]. Despite the very rich far-from-equilibrium evolution, we find
      surprising regularities in the form of clear correlations between initial entropy
      and total produced entropy, as well as between initial entropy and the
      temperature at thermalization, understood as the transition to a hydrodynamic
      description. For 29 different initial conditions that we consider, hydrodynamics
      turns out to be definitely applicable for proper times larger than 0.7 in units
      of inverse temperature at thermalization. We observe a sizable anisotropy in the
      energy-momentum tensor at thermalization, which is nevertheless entirely due to
      hydrodynamic effects. This suggests that effective thermalization in heavy-ion
      collisions may occur significantly earlier than true thermalization.

PMID- 23003143
TI  - Improved limit on direct alpha decay of the Hoyle state.
AB  - The current evaluation of the triple-alpha reaction rate assumes that the alpha
      decay of the 7.65 MeV, 0+ state in 12C, commonly known as the Hoyle state,
      proceeds sequentially via the ground state of 8Be. This assumption is challenged
      by the recent identification of two direct alpha-decay branches with a combined
      branching ratio of 17(5)%. If correct, this would imply a corresponding reduction
      in the triple-alpha reaction rate with important astrophysical consequences. We
      have used the 11B(3He,d) reaction to populate the Hoyle state and measured the
      decay to three alpha particles in complete kinematics. We find no evidence for
      direct alpha-decay branches, and hence our data do not support a revision of the
      triple-alpha reaction rate. We obtain an upper limit of 5*10(-3) on the direct
      alpha decay of the Hoyle state at 95% C.L., which is 1 order of magnitude better
      than a previous upper limit.

PMID- 23003144
TI  - Structure of 10He low-lying states uncovered by correlations.
AB  - The 0+ ground state of the 10He nucleus produced in the 3H(8He,p)10He reaction
      was found at about 2.1+/-0.2  MeV (Gamma~2  MeV) above the three-body ^{8}He+n+n
      breakup threshold. Angular correlations observed for ^{10}He decay products show
      prominent interference patterns allowing us to draw conclusions about the
      structure of low-energy excited states. We interpret the observed correlations as
      a coherent superposition of a broad 1- state having a maximum at energy 4-6 MeV
      and a 2+ state above 6 MeV, setting both on top of the 0+ state "tail." This
      anomalous level ordering indicates that the breakdown of the N=8 shell known in
      12Be thus extends also to the ^{10}He system.

PMID- 23003145
TI  - Role of the ionic potential in high harmonic generation.
AB  - Recollision processes provide direct insight into the structure and dynamics of
      electronic wave functions. However, the strength of the process sets its basic
      limitations--the interaction couples numerous degrees of freedom. In this Letter
      we decouple the basic steps of the process and resolve the role of the ionic
      potential which is at the heart of a broad range of strong field phenomena.
      Specifically, we measure high harmonic generation from argon atoms. By
      manipulating the polarization of the laser field we resolve the vectorial
      properties of the interaction. Our study shows that the ionic core plays a
      significant role in all steps of the interaction. In particular, Coulomb focusing
      induces an angular deflection of the electrons before recombination. A complete
      spatiospectral analysis reveals the influence of the potential on the
      spatiotemporal properties of the emitted light.

PMID- 23003146
TI  - Chemical reactions of atomic lithium and molecular calcium monohydride at 1 K.
AB  - Using cryogenic helium buffer-gas cooling, we have prepared dense samples of
      atomic lithium and molecular calcium monohydride at temperatures as low as 1 K.
      We have measured the Li+CaH->LiH+Ca chemical reaction, observed in both the
      accelerated disappearance of CaH in the presence of high densities of lithium and
      in the appearance of the LiH molecule.

PMID- 23003147
TI  - Collective modes of coupled phase oscillators with delayed coupling.
AB  - We study the effects of delayed coupling on timing and pattern formation in
      spatially extended systems of dynamic oscillators. Starting from a discrete
      lattice of coupled oscillators, we derive a generic continuum theory for
      collective modes of long wavelengths. We use this approach to study spatial phase
      profiles of cellular oscillators in the segmentation clock, a dynamic patterning
      system of vertebrate embryos. Collective wave patterns result from the interplay
      of coupling delays and moving boundary conditions. We show that the phase
      profiles of collective modes depend on coupling delays.

PMID- 23003148
TI  - Spatial pinning control.
AB  - In this Letter, we introduce the concept of spatial pinning control for a network
      of mobile chaotic agents. In a planar space, N agents move as random walkers and
      interact according to a time-varying r-disk proximity graph. A control input is
      applied only to those agents which enter a given area, called control region. The
      control is effective in driving all the agents to a reference evolution and has
      better performance than pinning control on a fixed set of agents. We derive
      analytical conditions on the relative size of the control region and the agent
      density for the global convergence of the system to the reference evolution and
      study the system under different regimes inherited by the velocity.

PMID- 23003149
TI  - Air entrainment by contact lines of a solid plate plunged into a viscous fluid.
AB  - The entrainment of air by advancing contact lines is studied by plunging a solid
      plate into a very viscous liquid. Above a threshold velocity, we observe the
      formation of an extended air film, typically 10 microns thick, which subsequently
      decays into air bubbles. Exploring a large range of viscous liquids, we find an
      unexpectedly weak dependence of entrainment speed on liquid viscosity, pointing
      towards a crucial role of the flow inside the air film. This induces a striking
      asymmetry between wetting and dewetting: while the breakup of the air film
      strongly resembles the dewetting of a liquid film, the wetting speeds are larger
      by orders of magnitude.

PMID- 23003150
TI  - Electrostatic response of a two-component plasma with Coulomb collisions.
AB  - A rigorous procedure is proposed for finding a solution to kinetic equations with
      the Landau electron-electron, electron-ion, ion-electron, and ion-ion collision
      integrals in fully ionized plasma. The linear plasma response to the perturbation
      in the electrostatic field is described in terms of plasma dielectric
      permittivity. Solutions of the dispersion relation for electron plasma waves, ion
      acoustic waves, and entropy modes are found in the entire range of frequencies,
      wave vectors, and particle collisionality. Several fits are obtained to enable
      practical applications of these results.

PMID- 23003151
TI  - Experimental realization of plaquette resonating valence-bond states with
      ultracold atoms in optical superlattices.
AB  - The concept of valence-bond resonance plays a fundamental role in the theory of
      the chemical bond and is believed to lie at the heart of many-body quantum
      physical phenomena. Here we show direct experimental evidence of a time-resolved
      valence-bond quantum resonance with ultracold bosonic atoms in an optical
      lattice. By means of a superlattice structure we create a three-dimensional array
      of independent four-site plaquettes, which we can fully control and manipulate in
      parallel. Moreover, we show how small-scale plaquette resonating valence-bond
      (RVB) states with s- and d-wave symmetry can be created and characterized. We
      anticipate our findings to open the path towards the creation and analysis of
      many-body RVB states in ultracold atomic gases.

PMID- 23003138
TI  - First evidence of direct CP violation in charmless two-body decays of Bs0 mesons.
AB  - Using a data sample corresponding to an integrated luminosity of 0.35  fb-1
      collected by LHCb in 2011, we report the first evidence of CP violation in the
      decays of Bs0} mesons to K+/-pi? pairs, ACP(Bs0->Kpi)=0.27+/-0.08(stat)+/
      0.02(syst), with a significance of 3.3sigma. Furthermore, we report the most
      precise measurement of CP violation in the decays of B0 mesons to K+/-pi? pairs,
      ACP(B0->Kpi)=-0.088+/-0.011(stat)+/-0.008(syst), with a significance exceeding
      6sigma.

PMID- 23003152
TI  - Formation of NaCl-type monodeuteride LaD by the disproportionation reaction of
      LaD2.
AB  - Previous x-ray diffraction measurements revealed the pressure-induced
      decomposition of an fcc LaH2.3 into H-rich and H-poor fcc phases around 11 GPa.
      The present neutron diffraction measurements on LaD2 confirm the formation of
      NaCl-type LaD as a counterpart of the D-rich LaD2+delta by disproportionation.
      First-principles enthalpy and lattice dynamic calculations demonstrate that the
      NaCl-type LaH is stabilized at high pressures and can be recovered at ambient
      conditions. Finding the NaCl-type LaH will pave the way for investigations on the
      site-dependent nature of hydrogen-metal interactions.

PMID- 23003153
TI  - Mechanical annealing of metallic electrodes at the atomic scale.
AB  - The process of creating an atomically defined and robust metallic tip is
      described and quantified using measurements of contact conductance between gold
      electrodes and numerical simulations. Our experiments show how the same
      conductance behavior can be obtained for hundreds of cycles of formation and
      rupture of the nanocontact by limiting the indentation depth between the two
      electrodes up to a conductance value of approximately 5G0 in the case of gold.
      This phenomenon is rationalized using molecular dynamics simulations together
      with density functional theory transport calculations which show how, after
      repeated indentations (mechanical annealing), the two metallic electrodes are
      shaped into tips of reproducible structure. These results provide a crucial
      insight into fundamental aspects relevant to nanotribology or scanning probe
      microscopies.

PMID- 23003154
TI  - Observation of microscale superlubricity in graphite.
AB  - Upon shearing a microscale lithographically defined graphite mesa, the sheared
      section retracts spontaneously to minimize interface energy. Here, we demonstrate
      a sixfold symmetry of the self-retraction and provide a first experimental
      estimate of the frictional force involved, as direct evidence that the self
      retraction is due to superlubricity, where ultralow friction occurs between
      incommensurate surfaces. The effect is remarkable because it occurs reproducibly
      under ambient conditions and over a contact area of up to 10*10  MUm2, more than
      7 orders of magnitude larger than previous scanning-probe-based studies of
      superlubricity in graphite. By analyzing the sheared interface, we show how the
      grain structure of highly oriented pyrolitic graphite determines the probability
      of self-retraction. Our results demonstrate that such self-retraction provides a
      novel probe of superlubricity, and the robustness of the phenomenon opens the way
      for practical applications of superlubricity in micromechanical systems.

PMID- 23003155
TI  - Evolution of fractal structures in dislocation ensembles during plastic
      deformation.
AB  - Based on the irreversible thermodynamics approach to dislocation plasticity of
      metals, a simple description of the dislocation density evolution and strain
      hardening was suggested. An analytical expression for the fractal dimension (FD)
      of a cellular (or tangled) dislocation structure evolving in the course of
      plastic deformation was obtained on the basis of the dislocation model proposed.
      This makes it possible to trace the variation of FD of the dislocation cell
      structure with strain by just measuring the macroscopic stress-strain curve. The
      FD behavior predicted in this way showed good agreement with the experimentally
      measured FD evolution at different stages of deformation of a Ni single crystal
      and a Cu polycrystal. One new result following from the present model is that the
      FD of the bulk dislocation structure in a deforming metal peaks at a certain
      strain close to the onset of necking. The significance of fractal analysis as an
      informative index to follow the spatial evolution of dislocation structures
      approaching the critical state is highlighted.

PMID- 23003156
TI  - Novel structural motifs in low energy phases of LiAlH4.
AB  - We identify a class of novel low energy phases of the hydrogen storage material
      LiAlH4 by using the ab initio minima hopping crystal structure prediction method.
      These phases are, unlike previous predictions and known structures of similar
      materials, characterized by polymeric networks consisting of Al atoms interlinked
      with H atoms. The most stable structure is a layered ionic crystal with P21/c
      symmetry, and it has lower free energy than the previously reported structure
      over a wide range of temperatures. Furthermore, we carry out x-ray diffraction,
      phonon, and GW band-structure analysis in order to characterize this phase. Its
      experimental synthesis would have profound implications for the study of
      dehydrogenation and rehydrogenation processes and the stability problem of LiAlH4
      for hydrogen storage applications.

PMID- 23003141
TI  - Search for a dark matter candidate produced in association with a single top
      quark in pp collisions at ?[s]=1.96  TeV.
AB  - We report a new search for dark matter in a data sample of an integrated
      luminosity of 7.7  fb-1 of Tevatron pp[over -] collisions at ?[s]=1.96  TeV,
      collected by the CDF II detector. We search for production of a dark-matter
      candidate, D, in association with a single top quark. We consider the hadronic
      decay mode of the top quark exclusively, yielding a final state of three jets
      with missing transverse energy. The data are consistent with the standard model;
      we thus set 95% confidence level upper limits on the cross section of the process
      pp[over -]->t+D as a function of the mass of the dark-matter candidate. The
      limits are approximately 0.5 pb for a dark-matter particle with mass in the range
      of 0-150  GeV/c2.

PMID- 23003157
TI  - Frustration of the isotropic-columnar phase transition of colloidal hard
      platelets by a transient cubatic phase.
AB  - Using simulations and theory, we show that the cubatic phase is metastable for
      three model hard platelets. The locally favored structures of perpendicular
      particle stacks in the fluid prevent the formation of the columnar phase through
      geometric frustration resulting in vitrification. Also, we find a direct link
      between structure and dynamic heterogeneities in the cooperative rotation of
      particle stacks, which is crucial for the devitrification process. Finally, we
      show that the lifetime of the glassy cubatic phase can be tuned by surprisingly
      small differences in particle shape.

PMID- 23003158
TI  - X-ray reflectivity at polarized liquid-Hg-aqueous-electrolyte interface:
      challenging macroscopic approaches for ion-specificity issues.
AB  - We report Angstrom-resolved x-ray reflectivity analysis of externally polarized
      liquid-Hg surface in contact with molar LiCl, LiBr, and MgSO4 aqueous
      electrolytes. Interpretation of reflectivity curves demonstrates a dependence of
      Hg-surface layering on both applied potential and ion nature. It further
      highlights how interfacial polarization degree impacts electron density profiles
      at a molecular scale. These profiles indicate accumulation of anions and cations
      at the Hg surface. Upon decrease of the potential from the point of zero charge,
      anions are gradually expelled from the Hg surface. The study challenges
      traditional thermodynamic approaches for deriving countercharge composition at
      the Hg-electrolyte-solution interface from macroscopic Hg-surface tension data.
      It further dismisses the long-standing approximation that assimilates the Hg
      surface to a smooth, perfect chemically inert conductor with a uniformly smeared
      out surface charge density.

PMID- 23003142
TI  - Directed flow of identified particles in Au+Au collisions at ?[SNN]=200  GeV at
      RHIC.
AB  - STAR's measurements of directed flow (v1) around midrapidity for pi+/-, K+/-,
      KS0, p, and p[over -] in Au+Au collisions at ?[sNN]=200  GeV are presented. A
      negative v1(y) slope is observed for most of produced particles (pi+/-, K+/-,
      KS0, and p[over -]). In 5%-30% central collisions, a sizable difference is
      present between the v1(y) slope of protons and antiprotons, with the former being
      consistent with zero within errors. The v1 excitation function is presented.
      Comparisons to model calculations (RQMD, UrQMD, AMPT, QGSM with parton
      recombination, and a hydrodynamics model with a tilted source) are made. For
      those models which have calculations of v1 for both pions and protons, none of
      them can describe v1(y) for pions and protons simultaneously. The hydrodynamics
      model with a tilted source as currently implemented cannot explain the centrality
      dependence of the difference between the v1(y) slopes of protons and antiprotons.

PMID- 23003159
TI  - Inhomogeneous relaxation of a molecular layer on an insulator due to compressive
      stress.
AB  - We discuss the inhomogeneous stress relaxation of a monolayer of
      hexahydroxytriphenylene (HHTP) which adopts the rare line-on-line (LOL)
      coincidence on KCl(001) and forms moire patterns. The fact that the hexagonal
      HHTP layer is uniaxially compressed along the LOL makes this system an ideal
      candidate to discuss the influence of inhomogeneous stress relaxation. Our work
      is a combination of noncontact atomic force microscopy experiments, density
      functional theory and potential energy calculations, and a thorough
      interpretation by means of the Frenkel-Kontorova model. We show that the
      assumption of a homogeneous molecular layer is not valid for this organic
      inorganic heteroepitaxial system since the best calculated energy configuration
      correlates with the experimental data only if inhomogeneous relaxations of the
      layer are taken into account.

PMID- 23003140
TI  - Measurement of Bs0->Ds(*)+Ds(*)- branching ratios.
AB  - The decays Bs0->Ds(*)+Ds(*)- are reconstructed in a data sample corresponding to
      an integrated luminosity of 6.8  fb-1 collected by the CDF II detector at the
      Tevatron pp[over -] collider. All decay modes are observed with a significance of
      more than 10sigma, and we measure the Bs0 production rate times Bs0->Ds(*)+Ds(*)-
      branching ratios relative to the normalization mode B0->Ds+D-to be 0.183+/
      0.021+/-0.017 for Bs0->Ds+Ds-, 0.424+/-0.046+/-0.035 for Bs0->Ds*+/-Ds^?, 0.654+/
      0.072+/-0.065 for Bs0->Ds*+Ds*-, and 1.261+/-0.095+/-0.112 for the inclusive
      decay Bs0->Ds(*)+Ds(*)-, where the uncertainties are statistical and systematic.
      These results are the most precise single measurements to date and provide
      important constraints for indirect searches for nonstandard model physics in Bs0
      mixing.

PMID- 23003160
TI  - Dynamic stabilization of the optical resonances of single nitrogen-vacancy
      centers in diamond.
AB  - We report electrical tuning by the Stark effect of the excited-state structure of
      single nitrogen-vacancy (NV) centers located ?100  nm from the diamond surface.
      The zero-phonon line (ZPL) emission frequency is controllably varied over a range
      of 300 GHz. Using high-resolution emission spectroscopy, we observe electrical
      tuning of the strengths of both cycling and spin-altering transitions. Under
      resonant excitation, we apply dynamic feedback to stabilize the ZPL frequency.
      The transition is locked over several minutes and drifts of the peak position on
      timescales ?100  ms are reduced to a fraction of the single-scan linewidth, with
      standard deviation as low as 16 MHz (obtained for an NV in bulk, ultrapure
      diamond). These techniques should improve the entanglement success probability in
      quantum communications protocols.

PMID- 23003161
TI  - STM imaging of impurity resonances on Bi2Se3.
AB  - In this Letter we present detailed study of the density of states near defects in
      Bi2Se3. In particular, we present data on the commonly found triangular defects
      in this system. While we do not find any measurable quasiparticle scattering
      interference effects, we do find localized resonances, which can be well fitted
      by theory [R. R. Biswas and A. V. Balatsky, Phys. Rev. B 81, 233405(R) (2010)]
      once the potential is taken to be extended to properly account for the observed
      defects. The data together with the fits confirm that while the local density of
      states around the Dirac point of the electronic spectrum at the surface is
      significantly disrupted near the impurity by the creation of low-energy resonance
      state, the Dirac point is not locally destroyed. We discuss our results in terms
      of the expected protected surface state of topological insulators.

PMID- 23003162
TI  - Experimental evidence of cubic Rashba effect in an inversion-symmetric oxide.
AB  - We present evidence of cubic Rashba spin splitting in a quasi-two-dimensional
      electron gas formed at a surface of (001) SrTiO3 single crystal from the weak
      localization or antilocalization (WAL) analysis of the low-temperature
      magnetoresistance. Our WAL data were well fitted by the model assuming mj=+/-3/2
      for the spin-split pair, in which 2pi rotation of the electron wave vector k? in
      the kx-ky plane accompanies 6pi rotation of the spin quantization axis. This
      finding pertains to the p symmetry of the t2g electronic band derived from d
      electrons in SrTiO3, which provides insights into the surface electronic state of
      (001) SrTiO3.

PMID- 23003163
TI  - Complex spin texture in the pure and Mn-doped topological insulator Bi2Te3.
AB  - Topological insulators are characterized by the presence of spin-momentum-locked
      surface states with Dirac points that span the fundamental bulk band gap. We show
      by first-principles calculations that the surface state of the insulator Bi2Te3
      survives upon moderate Mn doping of the surface layers. The spin texture of both
      undoped and Mn-doped Bi2Te3 is much more complicated than commonly believed,
      showing layer-dependent spin reversal and spin vortices.

PMID- 23003164
TI  - Effective control of the charge and magnetic states of transition-metal atoms on
      single-layer boron nitride.
AB  - Developing approaches to effectively control the charge and magnetic states is
      critical to the use of magnetic nanostructures in quantum information devices but
      is still challenging. Here we suggest that the magnetic and charge states of
      transition-metal (TM) doped single-layer boron-nitride (SLBN) systems can be
      easily controlled by the (internal) defect engineering and (external) electric
      fields (Eext). The relative positions and symmetries of the in-gap levels induced
      by defect engineering and the TM d-orbital energy levels effectively determine
      the charge states and magnetic properties of the TM/SLBN system. Remarkably, the
      application of an Eext can easily control the size of the crystal field splitting
      of the TM d orbitals and thus, leading to the spin crossover in TM/SLBN, which
      could be used as Eext-driven nonvolatile memory devices. Our conclusion obtained
      from TM/SLBN is valid generally in other TM adsorbed layered semiconductors.

PMID- 23003165
TI  - Experimental verification of PbBi2Te4 as a 3D topological insulator.
AB  - The experimental evidence is presented of the topological insulator state in
      PbBi2Te4. A single surface Dirac cone is observed by angle-resolved photoemission
      spectroscopy with synchrotron radiation. Topological invariants Z2 are calculated
      from the ab initio band structure to be 1;(111). The observed two-dimensional
      isoenergy contours in the bulk energy gap are found to be the largest among the
      known three-dimensional topological insulators. This opens a pathway to achieving
      a sufficiently large spin current density in future spintronic devices.

PMID- 23003166
TI  - Probing fractional topological insulators with magnetic edge perturbations.
AB  - We discuss detection strategies for fractional topological insulators (FTIs)
      realizing time-reversal invariant analogues of fractional quantum Hall systems in
      the Laughlin universality class. Focusing on transport measurements, we study the
      effect of magnetic perturbations on the edge modes. We find that the modes show
      unexpected robustness against magnetic backscattering for moderate couplings and
      edge interactions, allowing for various phase transitions signaling the FTI
      phase. We also describe protocols for extracting the universal integer m
      characterizing the phase and the edge interaction parameter from the conductance
      of setups with magnets and a quantum point contact.

PMID- 23003167
TI  - Local gating of an Ir(111) surface resonance by graphene islands.
AB  - The influence of graphene islands on the electronic structure of the Ir(111)
      surface is investigated. Scanning tunneling spectroscopy (STS) indicates the
      presence of a two-dimensional electron gas with a binding energy of -160  meV and
      an effective mass of -0.18me underneath single-layer graphene on the Ir(111)
      surface. Density functional calculations reveal that the STS features are
      predominantly due to a holelike surface resonance of the Ir(111) substrate.
      Nanometer-sized graphene islands act as local gates, which shift and confine the
      surface resonance.

PMID- 23003168
TI  - Statistics of reflection eigenvalues in chaotic cavities with nonideal leads.
AB  - The scattering matrix approach is employed to determine a joint probability
      density function of reflection eigenvalues for chaotic cavities coupled to the
      outside world through both ballistic and tunnel point contacts. Derived under
      assumption of broken time-reversal symmetry, this result is further utilized to
      (i) calculate the density and correlation functions of reflection eigenvalues,
      and (ii) analyze fluctuations properties of the Landauer conductance for the
      illustrative example of asymmetric chaotic cavity. Further extensions of the
      theory are pinpointed.

PMID- 23003169
TI  - Kondo effect of magnetic impurities in nanotubes.
AB  - Transition metal impurities will yield zero-bias anomalies in the conductance of
      well contacted metallic carbon nanotubes, but Kondo temperatures and geometry
      dependences have not been anticipated so far. Applying the density functional
      plus numerical renormalization group approach of Lucignano et al. to Co and Fe
      impurities in (4,4) and (8,8) nanotubes, we discover a huge difference of
      behavior between outside versus inside adsorption of the impurity. The predicted
      Kondo temperatures and zero-bias anomalies, tiny outside the nanotube, turn large
      and strongly radius dependent inside, owing to a change of symmetry of the
      magnetic orbital. Observation of this Kondo effect should open the way to a host
      of future experiments.

PMID- 23003170
TI  - Elliot-Yafet mechanism in graphene.
AB  - The differences between spin relaxation in graphene and in other materials are
      discussed. For relaxation by scattering processes, the Elliot-Yafet mechanism,
      the relation between the spin and the momentum scattering times, acquires a
      dependence on the carrier density, which is independent of the scattering
      mechanism and the relation between mobility and carrier concentration. This
      dependence puts severe restrictions on the origin of the spin relaxation in
      graphene. The density dependence of the spin relaxation allows us to distinguish
      between ordinary impurities and defects which modify locally the spin-orbit
      interaction.

PMID- 23003171
TI  - Fractional quantum Hall states of photons in an array of dissipative coupled
      cavities.
AB  - We report a theoretical study of the collective optical response of a two
      dimensional array of nonlinear cavities in the impenetrable photon regime under a
      strong artificial magnetic field. Taking advantage of the nonequilibrium nature
      of the photon gas, we propose an experimentally viable all-optical scheme to
      generate and detect strongly correlated photon states which are optical analogs
      of the Laughlin states of fractional quantum Hall physics.

PMID- 23003172
TI  - Nonlinear hydrodynamics and fractionally quantized solitons at the fractional
      quantum Hall edge.
AB  - We argue that the dynamics of fractional quantum Hall (FQH) edge states is
      essentially nonlinear and that it features fractionally quantized solitons with
      charges -nue propagating along the edge. The observation of solitons would be
      direct evidence of fractional charges. We show that the nonlinear dynamics of the
      Laughlin's FQH state is governed by the quantum Benjamin-Ono equation. Nonlinear
      dynamics of gapless edge states is determined by gapped modes in the bulk of FQH
      liquid and is traced to the double boundary layer "overshoot" of FQH states. The
      dipole moment of the layer eta=1-nu/4pi is obtained in paper. Quantum
      hydrodynamics of FQH liquid is outlined.

PMID- 23003173
TI  - Spin-orbit-induced strong coupling of a single spin to a nanomechanical
      resonator.
AB  - We theoretically investigate the deflection-induced coupling of an electron spin
      to vibrational motion due to spin-orbit coupling in suspended carbon nanotube
      quantum dots. Our estimates indicate that, with current capabilities, a quantum
      dot with an odd number of electrons can serve as a realization of the Jaynes
      Cummings model of quantum electrodynamics in the strong-coupling regime. A
      quantized flexural mode of the suspended tube plays the role of the optical mode
      and we identify two distinct two-level subspaces, at small and large magnetic
      field, which can be used as qubits in this setup. The strong intrinsic spin
      mechanical coupling allows for detection, as well as manipulation of the spin
      qubit, and may yield enhanced performance of nanotubes in sensing applications.

PMID- 23003174
TI  - Detection of a large valley-orbit splitting in silicon with two-donor
      spectroscopy.
AB  - We measure a large valley-orbit splitting for shallow isolated phosphorus donors
      in a silicon gated nanowire. This splitting is close to the bulk value and well
      above previous reports in silicon nanostructures. It was determined using a
      double dopant transport spectroscopy which eliminates artifacts induced by the
      environment. Quantitative simulations taking into account the position of the
      donors with respect to the Si/SiO2 interface and electric field in the wire show
      that the values found are consistent with the device geometry.

PMID- 23003175
TI  - Critical velocity of a mobile impurity in one-dimensional quantum liquids.
AB  - We study the notion of superfluid critical velocity in one spatial dimension. It
      is shown that, for heavy impurities with mass M exceeding a critical mass Mc, the
      dispersion develops periodic metastable branches resulting in dramatic changes of
      dynamics in the presence of an external driving force. In contrast to smooth
      Bloch oscillations for M<Mc, a heavy impurity climbs metastable branches until it
      reaches a branch termination point or undergoes a random tunneling event, both
      leading to an abrupt change in velocity and an energy loss. This is predicted to
      lead to a nonanalytic dependence of the impurity drift velocity on small forces.

PMID- 23003176
TI  - Two-band superconductors: hidden criticality deep in the superconducting state.
AB  - We show that two-band superconductors harbor hidden criticality deep in the
      superconducting state, stemming from the critical temperature of the weaker band
      taken as an independent system. For sufficiently small interband coupling gamma
      the coherence length of the weaker band exhibits a remarkable deviation from the
      conventional monotonic increase with temperature, namely, a pronounced peak close
      to the hidden critical point. The magnitude of the peak scales as ?gamma-MU, with
      the Landau critical exponent MU=1/3, the same as found for the mean-field
      critical behavior with respect to the source field in ferromagnets and
      ferroelectrics. Here reported hidden criticality of multiband superconductors can
      be experimentally observed by, e.g., imaging of the variations of the vortex core
      in a broader temperature range. Similar effects are expected for the
      superconducting multilayers.

PMID- 23003177
TI  - Do transition-metal substitutions dope carriers in iron-based superconductors?
AB  - We investigate the currently debated issue concerning whether transition-metal
      substitutions dope carriers in iron-based superconductors. From first-principles
      calculations of the configuration-averaged spectral function of BaFe2As2 with
      disordered Co or Zn substitutions of Fe, important doping effects are found
      beyond merely changing the carrier density. While the chemical potential shifts
      suggest doping of a large amount of carriers, a reduction of the coherent carrier
      density is found due to the loss of spectral weight. Therefore, none of the
      change in the Fermi surface, density of states, or charge distribution can be
      solely used for counting doped coherent carriers, let alone presenting the full
      effects of the disordered substitutions. Our study highlights the necessity of
      including disorder effects in the studies of doped materials in general.

PMID- 23003178
TI  - Superfluid density and phase relaxation in superconductors with strong disorder.
AB  - We consider the attractive Hubbard model with on-site disorder as a prototype of
      a disordered superconductor. We solve the Bogoliubov-de Gennes equations on two
      dimensional finite clusters at zero temperature and evaluate the electromagnetic
      response to a vector potential. We find that the standard decoupling between
      transverse and longitudinal response does not apply in the presence of disorder.
      Moreover, the superfluid density is strongly reduced by the relaxation of the
      phase of the order parameter already at mean-field level when disorder is large.
      We also find that the anharmonicity of the phase fluctuations is strongly
      enhanced by disorder. Beyond mean field, this provides an enhancement of quantum
      fluctuations inducing a zero-temperature transition to a nonsuperconducting phase
      of disordered preformed pairs. Finally, the connection of our findings with the
      glassy physics for extreme dirty superconductors is discussed.

PMID- 23003179
TI  - In-plane magnetic field anisotropy of the Fulde-Ferrell-Larkin-Ovchinnikov state
      in layered superconductors.
AB  - There is strong experimental evidence of the Fulde-Ferrell-Larkin-Ovchinnikov
      (FFLO) state formation in layered organic superconductors in a parallel magnetic
      field. We study theoretically the interplay between the orbital effect and the
      FFLO modulation in this case and demonstrate that the in-plane critical field
      anisotropy drastically changes at the transition to the FFLO state. The very
      peculiar angular dependence of the superconducting onset temperature which is
      predicted may serve for unambiguous identification of the FFLO modulation. The
      obtained results permit us to suggest the modulated phase stabilization as the
      origin of the magnetic-field angle dependence of the onset of superconductivity
      experimentally observed in (TMTSF)2ClO4 organic conductors.

PMID- 23003180
TI  - Fractionalization of itinerant anyons in one-dimensional chains.
AB  - We construct models of interacting itinerant non-Abelian anyons moving along one
      dimensional chains, focusing, in particular, on itinerant Ising anyon chains, and
      derive effective anyonic t-J models for the low-energy sectors. Solving these
      models by exact diagonalization, we find a fractionalization of the anyons into
      charge and (non-Abelian) anyonic degrees of freedom--a generalization of spin
      charge separation of electrons which occurs in Luttinger liquids. A detailed
      description of the excitation spectrum by combining spectra for charge and
      anyonic sectors requires a subtle coupling between charge and anyonic excitations
      at the microscopic level (which we also find to be present in Luttinger liquids),
      despite the macroscopic fractionalization.

PMID- 23003181
TI  - Magnetic adatom induced Skyrmion-like spin texture in surface electron waves.
AB  - When a foreign atom is placed on a surface of a metal, the surrounding sea of
      electrons responds by screening the additional charge leading to oscillations or
      ripples. On surfaces, those electrons are sometimes confined to two-dimensional
      surface states, whose spin-degeneracy is lifted due to the Rashba effect arising
      from the spin-orbit interaction of electrons and the inversion asymmetric
      environment. It is believed that at least for a single adatom scanning tunneling
      microscopy measurements are insensitive to the Rashba splitting; i.e., no
      signatures in the charge oscillations will be observed. Resting on scattering
      theory, we demonstrate that, if magnetic, one single adatom is enough to
      visualize the presence of the Rashba effect in terms of an induced spin
      magnetization of the surrounding electrons exhibiting a twisted spin texture
      described as superposition of two Skyrmionic waves of opposite chirality.

PMID- 23003182
TI  - Decoherence and mode hopping in a magnetic tunnel junction based spin torque
      oscillator.
AB  - We discuss the coherence of magnetic oscillations in a magnetic tunnel junction
      based spin torque oscillator as a function of the external field angle. Time
      frequency analysis shows mode hopping between distinct oscillator modes, which
      arises from linear and nonlinear couplings in the Landau-Lifshitz-Gilbert
      equation, analogous to mode hopping observed in semiconductor ring lasers. These
      couplings and, therefore, mode hopping are minimized near the current threshold
      for the antiparallel alignment of free-layer with reference layer magnetization.
      Away from the antiparallel alignment, mode hopping limits oscillator coherence.

PMID- 23003183
TI  - Kagome antiferromagnet: a chiral topological spin liquid?
AB  - Inspired by the recent discovery of a new instability towards a chiral phase of
      the classical Heisenberg model on the kagome lattice, we propose a specific
      chiral spin liquid that reconciles different, well-established results concerning
      both the classical and quantum models. This proposal is analyzed in an extended
      mean-field Schwinger boson framework encompassing time reversal symmetry breaking
      phases, which allows both a classical and a quantum phase description. At low
      temperatures, we find that quantum fluctuations favor this chiral phase, which is
      stable against small perturbations of second- and third-neighbor interactions.
      For spin-1/2, this phase may be, beyond the mean field, a chiral gapped spin
      liquid. Such a phase is consistent with the density matrix renormalization group
      results of Yan et al. [Science 332, 1173 (2011)]. Mysterious features of the low
      lying excitations of exact diagonalization spectra also find an explanation in
      this framework. Moreover, thermal fluctuations compete with quantum ones and
      induce a transition from this flux phase to a planar zero flux phase at a nonzero
      value of the renormalized temperature (T/S2), reconciling these results with
      those obtained for the classical system.

PMID- 23003184
TI  - Effect of interface-induced exchange fields on cuprate-manganite spin switches.
AB  - We examine the anomalous inverse spin switch behavior in
      La0.7Ca0.3MnO3(LCMO)/YBa2Cu3O7-delta (YBCO)/LCMO trilayers by combined transport
      studies and polarized neutron reflectometry. Measuring magnetization profiles and
      magnetoresistance in an in-plane rotating magnetic field, we prove that, contrary
      to many accepted theoretical scenarios, the relative orientation between the two
      LCMO's magnetizations is not sufficient to determine the magnetoresistance.
      Rather the field dependence of magnetoresistance is explained by the interplay
      between the applied magnetic field and the (exponential tail of the) induced
      exchange field in YBCO, the latter originating from the electronic reconstruction
      at the LCMO/YBCO interfaces.

PMID- 23003185
TI  - Chemical pressure effects on pyrochlore spin ice.
AB  - A comparison among the two sets of studied pyrochlore spin ices, Ho2Sn2O7,
      Ho2Ti2O7, and Ho2Ge2O7 with Ho3+ spins and Dy2Sn2O7, Dy2Ti2O7, and Dy2Ge2O7 with
      Dy3+ spins, shows that the application of chemical pressure through each set
      drives the system toward the antiferromagnetic phase boundary from the spin ice
      region, which agrees with the prediction of the "dipolar spin ice" model of den
      Hertog and Gingras. Among all the studied pyrochlore spin ices, Dy2Ge2O7 has the
      smallest ratio of Jnn/Dnn=-0.73.

PMID- 23003186
TI  - Solvation and evolution dynamics of an excess electron in supercritical CO2.
AB  - We present an ab initio molecular dynamics simulation of the dynamics of an
      excess electron solvated in supercritical CO2. The excess electron can exist in
      three types of states: CO2-core localized, dual-core localized, and diffuse
      states. All these states undergo continuous state conversions via a combination
      of long lasting breathing oscillations and core switching, as also characterized
      by highly cooperative oscillations of the excess electron volume and vertical
      detachment energy. All of these oscillations exhibit a strong correlation with
      the electron-impacted bending vibration of the core CO2, and the core-switching
      is controlled by thermal fluctuations.

PMID- 23003187
TI  - Ab initio molecular dynamics study of dissociation of water under an electric
      field.
AB  - The behavior of liquid water under an electric field is a crucial phenomenon in
      science and engineering. However, its detailed description at a microscopic level
      is difficult to achieve experimentally. Here we report on the first ab initio
      molecular-dynamics study on water under an electric field. We observe that the
      hydrogen-bond length and the molecular orientation are significantly modified at
      low-to-moderate field intensities. Fields beyond a threshold of about 0.35  V/A
      are able to dissociate molecules and sustain an ionic current via a series of
      correlated proton jumps. Upon applying even more intense fields (~1.0  V/A), a
      15%-20% fraction of molecules are instantaneously dissociated and the resulting
      ionic flow yields a conductance of about 7.8  Omega-1 cm-1, in good agreement
      with experimental values. This result paves the way to quantum-accurate
      microscopic studies of the effect of electric fields on aqueous solutions and,
      thus, to massive applications of ab initio molecular dynamics in neurobiology,
      electrochemistry, and hydrogen economy.

PMID- 23003188
TI  - Confinement-induced transition of topological defects in smectic liquid crystals:
      from a point to a line and pearls.
AB  - We report a study on the confinement-induced transition of the topological
      defects of liquid crystals (LCs) using smectic-A LCs confined in prolate
      spheroids with homeotropic anchoring. Upon increasing the aspect ratio of a LC
      droplet, dispersed in a stretched elastomer film, the topological defect
      undergoes a transition from a point to a line of which the length is a function
      of the aspect ratio. Additionally, when the size of a droplet is larger than a
      certain value, the defect has a pearl-necklace-like texture. We propose a simple
      model to understand the formation of these defects in terms of the misorientation
      and undulation instability of the smectic layers.

PMID- 23003189
TI  - Extrinsic curvature effects on nematic shells.
AB  - When nematic liquid crystals are constrained to a curved surface, the geometry
      induces distortions in the molecular orientation. The mechanisms of the
      geometrical frustration involve the intrinsic as well as the extrinsic geometry
      of the underlying substrate. We show that the nematic elastic energy promotes the
      alignment of the flux lines of the nematic director towards geodesics and/or
      lines of curvature of the surface. As a consequence, the influence of the
      curvature can be tuned through the Frank elastic moduli. To illustrate this
      effect, we consider the simple case of nematics lying on a cylindrical shell. By
      combining the curvature effects with external magnetic fields, the molecular
      alignment can be reoriented or switched between two stable configurations. This
      enables the manipulation of nematic alignment for the design of new materials and
      technological devices.

PMID- 23003190
TI  - Entangled granular media.
AB  - We study the geometrically induced cohesion of ensembles of granular "u
      particles" that mechanically entangle through particle interpenetration. We vary
      the length-to-width ratio l/w of the u particles and form them into freestanding
      vertical columns. In a laboratory experiment, we monitor the response of the
      columns to sinusoidal vibration (with peak acceleration Gamma). Column collapse
      occurs in a characteristic time tau which follows the relation
      tau?exp(Gamma/Delta). Delta resembles an activation energy and is maximal at
      intermediate l/w. A simulation reveals that optimal strength results from
      competition between packing and entanglement.

PMID- 23003191
TI  - Distinct transport regimes for two elastically coupled molecular motors.
AB  - Cooperative cargo transport by two molecular motors involves an elastic motor
      motor coupling, which can reduce the motors' velocity and/or enhance their
      unbinding from the filament. We show theoretically that these interference
      effects lead, in general, to four distinct transport regimes. In addition to a
      weak coupling regime, kinesin and dynein motors are found to exhibit a strong
      coupling and an enhanced unbinding regime, whereas myosin motors are predicted to
      attain a reduced velocity regime. All of these regimes, which we derive by
      explicit calculations and general time scale arguments, can be explored
      experimentally by varying the elastic coupling strength.

PMID- 23003192
TI  - Universal critical dynamics in high resolution neuronal avalanche data.
AB  - The tasks of neural computation are remarkably diverse. To function optimally,
      neuronal networks have been hypothesized to operate near a nonequilibrium
      critical point. However, experimental evidence for critical dynamics has been
      inconclusive. Here, we show that the dynamics of cultured cortical networks are
      critical. We analyze neuronal network data collected at the individual neuron
      level using the framework of nonequilibrium phase transitions. Among the most
      striking predictions confirmed is that the mean temporal profiles of avalanches
      of widely varying durations are quantitatively described by a single universal
      scaling function. We also show that the data have three additional features
      predicted by critical phenomena: approximate power law distributions of avalanche
      sizes and durations, samples in subcritical and supercritical phases, and scaling
      laws between anomalous exponents.

PMID- 23003193
TI  - Adaptation to optimal cell growth through self-organized criticality.
AB  - A simple cell model consisting of a catalytic reaction network is studied to show
      that cellular states are self-organized in a critical state for achieving optimal
      growth; we consider the catalytic network dynamics over a wide range of
      environmental conditions, through the spontaneous regulation of nutrient
      transport into the cell. Furthermore, we find that the adaptability of cellular
      growth to reach a critical state depends only on the extent of environmental
      changes, while all chemical species in the cell exhibit correlated partial
      adaptation. These results are in remarkable agreement with the recent
      experimental observations of the present cells.

PMID- 23003194
TI  - Controlling the folding and substrate-binding of proteins using polymer brushes.
AB  - The extent of coupling between the folding of a protein and its binding to a
      substrate varies from protein to protein. Some proteins have highly structured
      native states in solution, while others are natively disordered and only fold
      fully upon binding. In this Letter, we use Monte Carlo simulations to investigate
      how disordered polymer chains grafted around a binding site affect the folding
      and binding of three model proteins. The protein that approaches the substrate
      fully folded is more hindered during the binding process than those whose folding
      and binding are cooperative. The polymer chains act as localized crowding agents
      and can select correctly folded and bound configurations in favor of
      nonspecifically adsorbed states. The free energy change for forming all
      intraprotein and protein-substrate contacts can depend nonmonotonically on the
      polymer length.

PMID- 23003195
TI  - Competition for shortest paths on sparse graphs.
AB  - Optimal paths connecting randomly selected network nodes and fixed routers are
      studied analytically in the presence of a nonlinear overlap cost that penalizes
      congestion. Routing becomes more difficult as the number of selected nodes
      increases and exhibits ergodicity breaking in the case of multiple routers. The
      ground state of such systems reveals nonmonotonic complex behaviors in average
      path length and algorithmic convergence, depending on the network topology, and
      densities of communicating nodes and routers. A distributed linearly scalable
      routing algorithm is also devised.

PMID- 23003196
TI  - Patients' intentions to inform relatives about Type 2 diabetes risk: the role of
      worry in the process of family risk disclosure.
AB  - AIMS: Patients with Type 2 diabetes may play a role as intermediary between
      medical professionals and at-risk relatives to promote diabetes prevention in
      their family. This study aimed to further our understanding of factors that
      influence the decisional process of familial risk disclosure in patients with
      diabetes. METHODS: In a cross-sectional study, patients with Type 2 diabetes (n =
      546) filled in a questionnaire assessing family risk perception, worry, personal
      beliefs regarding diabetes prevention, diabetes-related family communication,
      intention and perceived ability to inform relatives about familial risk of
      diabetes. Data were analysed using hierarchical logistic regression and multiple
      mediation analyses. RESULTS: Sixty per cent of the patients were willing to
      inform their relatives about familial diabetes risk; 61% reported high family
      risk perception and 41% had positive control beliefs with regard to preventive
      options in relatives. A majority (69%) did not express serious concern about
      relatives developing diabetes. Worry about relatives, knowing what to tell, whom
      to notify, and communication about diabetes in general appeared to facilitate
      family risk disclosure. Unexpectedly, high family risk perception in itself did
      not significantly increase patients' intentions to inform relatives; rather, risk
      perception appeared to exert an indirect effect through worry and beliefs about
      diabetes prevention. CONCLUSIONS: Worry in patients with diabetes appears to be a
      key factor in the process of family risk disclosure. When professionals guide
      their patients in this process, they should not only provide risk information,
      but also address worries and emphasize opportunities for diabetes prevention.

PMID- 23003197
TI  - Primary acinic cell carcinoma of the breast: a rare lesion with good prognosis.

PMID- 23003198
TI  - A rationally designed six-residue swap generates comparability in the aggregation
      behavior of alpha-synuclein and beta-synuclein.
AB  - The aggregation process of alpha-synuclein, a protein closely associated with
      Parkinson's disease, is highly sensitive to sequence variations. It is therefore
      of great importance to understand the factors that define the aggregation
      propensity of specific mutational variants as well as their toxic behavior in the
      cellular environment. In this context, we investigated the extent to which the
      aggregation behavior of alpha-synuclein can be altered to resemble that of beta
      synuclein, an aggregation-resistant homologue of alpha-synuclein not associated
      with disease, by swapping residues between the two proteins. Because of the vast
      number of possible swaps, we have applied a rational design procedure to single
      out a mutational variant, called alpha2beta, in which two short stretches of the
      sequence in the NAC region have been replaced in alpha-synuclein from beta
      synuclein. We find not only  that the aggregation rate of alpha2beta is close to
      that of beta-synuclein, being much lower than that of alpha-synuclein, but also
      that alpha2beta effectively changes the cellular toxicity of alpha-synuclein to a
      value similar to that of beta-synuclein upon exposure of SH-SY5Y cells to
      preformed oligomers. Remarkably, control experiments on the corresponding
      mutational variant of beta-synuclein, called beta2alpha, confirmed that the
      mutations that we have identified also shift the aggregation behavior of this
      protein toward that of alpha-synuclein. These results demonstrate that it is
      becoming possible to control in quantitative detail the sequence code that
      defines the aggregation behavior and toxicity of alpha-synuclein.

PMID- 23003199
TI  - Me-Si bond cleavage of anionic bis(trimethylsilyl)amide in scorpionate-anchored
      rare earth metal complexes.
AB  - A novel Tp(Me2)-supported (Tp(Me2) = tri(3,5-dimethylpyrazolyl)borate) rare earth
      metal complex promoted Me-Si cleavage of the bis(trimethylsilyl) amide ligand
      ([(Me(3)Si)(2)N](-)) was observed. Reaction of Tp(Me2)LnCl(2) with 2 equiv of
      K[(RN)(2)CN(SiMe(3))(2)] (KGua) gave the methylamidinate complexes
      Tp(Me2)Ln[(RN)(2)CMe][N(SiMe(3))(2)] (R = isopropyl, Ln = Y (1(Y)), Er (1(Er)); R
      = cyclohexyl, Ln = Y (2(Y))) in moderate yields. In contrast, Tp(Me2)YCl(2)(THF)
      reacted with 1 equiv of KGua to afford a C-N cleavage product
      Tp(Me2)Y(Cl)N(SiMe(3))(2)(THF) (4), indicating that this guanidinate ligand is
      not stable in the yttrium complex with the Tp(Me2) ligand, and a carbodiimide
      deinsertion takes place easily. The mechanism for the formation of complexes 1
      and 2 was also studied by controlling the substrate stoichiometry and the
      reaction sequence and revealed that the bis(trimethylsilyl)amine anion
      N(SiMe(3))(2)(-) can undergo two routes of gamma-methyl deprotonation and Si-Me
      cleavage for its functionalizations. All these new complexes were characterized
      by elemental analysis and spectroscopic methods, and their solid-state structures
      were also confirmed by single-crystal X-ray diffraction.

PMID- 23003201
TI  - Preparation and characterization of enteric microparticles by coacervation.
AB  - The aim of this study was to produce cinnarizine loaded Eudragit((r)) L100-55
      microparticles by coacervation technique in order to achieve pH responsive drug
      release using hydroxypropyl methycellulose (HPMC) as stabilizer. The effect of
      enteric polymer: HPMC ratio on properties of microparticles was investigated with
      regard to particle size distribution, morphology, yield, encapsulation
      efficiency, in vitro drug release profiles and interaction between cinnarizine
      and Eudragit((r)) L100-55. High drug encapsulation efficiency was seen in all
      microparticles. Particle diameter increased when the enteric polymer content was
      higher relative to HPMC. In vitro dissolution studies demonstrated that the drug
      release from the microparticles was dependent upon enteric polymer: HPMC ratio
      and particle size distribution. At the ratio of at least 3.75:1 of enteric
      polymer: HPMC, drug release was suppressed most significantly in low pH
      (hydrochloric acid as medium) while rapid drug release was observed in pH 7.4.

PMID- 23003200
TI  - Bicarbonate-dependent, carbonate radical anion-driven tocopherol-mediated human
      LDL peroxidation: an in vitro and in vivo study.
AB  - We have here investigated possible occurrence of bicarbonate-dependent, carbonate
      radical anion (CO(3)(*-))-driven tocopherol-mediated human LDL peroxidation (TMP)
      in vitro and in vivo. CO(3)(*-), generated in vitro by the
      SOD1/H(2)O(2)/bicarbonate system, readily promoted TMP, which was dependent on
      alpha-tocopherol and bicarbonate concentrations, and was inhibited by the CO(3)(*
      ) scavenger ethanol; moreover, TMP induced in vitro by the
      SOD1/H(2)O(2)/bicarbonate system occurred in the presence of alpha-tocopherol
      that typically underwent slow oxidative consumption. In the in vivo clinical
      setting, we showed that, compared to controls, hypertensive patients with
      diuretic-induced metabolic alkalosis and heightened blood bicarbonate
      concentration had lipid hydroperoxide burden and decreased alpha-tocopherol
      content in the LDL fraction, with direct significant correlation between the LDL
      levels of alpha-tocopherol and those of lipid hydroperoxides; remarkably, after
      resolution of metabolic alkalosis, together with normalization of blood
      bicarbonate concentration, the LDL content of lipid hydroperoxides was decreased
      and that of alpha-tocopherol augmented significantly. These findings suggest
      bicarbonate-dependent, CO(3)(*-)-driven LDL TMP in vivo. In conclusion, the
      present study highlights the occurrence of bicarbonate-dependent, CO(3)(*-)
      driven human LDL TMP, the role of which in pathological conditions such as
      atherosclerosis warrants, however, further investigation.

PMID- 23003202
TI  - Lapatinib and 17AAG reduce 89Zr-trastuzumab-F(ab')2 uptake in SKBR3 tumor
      xenografts.
AB  - Human epidermal growth factor receptor-2 (HER2) directed therapy potentially can
      be improved by insight in drug effects on HER2 expression. This study evaluates
      the effects of the EGFR/HER2 tyrosine kinase inhibitor lapatinib, the heat shock
      protein-90 inhibitor 17AAG, and their combination, on HER2 expression with in
      vivo HER2-PET imaging. Lapatinib and 17AAG effects on EGFR and HER2 membrane
      expression were determined in vitro using flow cytometry of human SKBR3 tumor
      cells. Effect of lapatinib on HER2 internalization was studied in vitro by (89)Zr
      trastuzumab-F(ab')(2) internalization. For in vivo evaluation, (89)Zr-trastuzumab
      F(ab')(2) MUPET imaging was performed two times with a 7 day interval. Lapatinib
      was administered for 6 days, starting 1 day after the baseline scan. 17AAG was
      given 1 day before the second (89)Zr-trastuzumab-F(ab')(2) injection. Imaging
      data were compared with ex vivo biodistribution analysis and HER2
      immunohistochemical staining. 17AAG treatment lowered EGFR expression by 41% (P =
      0.016) and HER2 by 76% (P = 0.022). EGFR/HER2 downregulation by 17AAG was
      inhibited by lapatinib pretreatment. Lapatinib reduced internalization of (89)Zr
      trastuzumab-F(ab')(2) with 25% (P = 0.0022). (89)Zr-trastuzumab-F(ab')(2) tumor
      to blood ratio was lowered 32% by lapatinib (P = 0.00004), 34% by 17AAG (P =
      0.0022) and even 53% by the combination (P = 0.011). Lapatinib inhibits HER2
      internalization and 17AAG lowers HER2 membrane expression. Both drugs reduce
      (89)Zr-trastuzumab-F(ab')(2) tumor uptake. Based on our findings, supported by
      previous preclinical data indicating the antitumor potency of lapatinib in
      combination with HSP90 inhibition, combination of these drugs deserves further
      investigation.

PMID- 23003204
TI  - Advances in catheter ablation: atrial fibrillation ablation in patients with
      mitral mechanical prosthetic valve.
AB  - Atrial fibrillation (AF) is common in patients with mitral valve replacement
      (MVR). Treatment of AF in these subjects is challenging, as the arrhythmia is
      often refractory to antiarrhythmic drug therapy. Radiofrequency catheter ablation
      (RFCA) is usually avoided or delayed in patients with MVR due to the higher
      perceived risks and difficulty of left atrial catheter manipulation in the
      presence of a mechanical valve. Over the last few years, several investigators
      have reported the feasibility and safety of RFCA of AF in patients with MVR. Five
      case-control studies have evaluated the feasibility and safety of RFCA of AF or
      perimitral flutter (PMFL) in patients with MVR. Overall, a total of 178 patients
      with MVR have been included (21 undergoing ablation of only PMFL), and have been
      compared with a matched control group of 285 patients. Total procedural duration
      (weighted mean difference [WMD] = +24.5 min, 95% confidence interval [CI] +10.2
      min to +38.8 min, P = 0.001), and fluoroscopy time (WMD = +13.5 min, 95% CI +3.7
      min to +23.4 min, P = 0.007) were longer in the MVR group. After a mean follow-up
      of 11.5 +/- 8.6 months, 64 (36%) patients in the MVR group experienced recurrence
      of AF/PMFL, as compared to 73 (26%) patients in the control group, accounting for
      a trend toward an increased rate of recurrences in patients with MVR (odds ratio
      [OR] = 1.66, 95% CI 0.99 to 2.78, P = 0.053). Periprocedural complications
      occurred in 10 (5.6%) patients in the MVR group, and in 8 (2.8%) patients in the
      control group (OR = 2.01, 95% CI 0.56 to 7.15, P = 0.28). In conclusion, a
      quantitative analysis of the available evidence supports a trend toward a worse
      arrhythmia-free survival and a higher absolute rate of periprocedural
      complications in patients with MVR undergoing RFCA of AF or PMFL, as compared to
      a matched control group without mitral valve disease. These data would encourage
      the adoption of RFCA of AF in MVR patients mostly by more experienced
      Institutions.

PMID- 23003203
TI  - Sleep apnea and atrial fibrillation; 2012 update.
AB  - Atrial fibrillation (AF) and obstructive sleep apnea (OSA) are very prevalent
      diseases in modern society. Recent years have seen the emergence of a wide body
      of literature suggesting an important association between these two diseases.
      This review will provide a summary of this evidence as it currently exists.
      First, it will review the literature suggesting an association between AF and OSA
      by highlighting the prevalence of AF in OSA, the correlation of AF prevalence
      with OSA severity and the trend towards increased AF recurrence in patients with
      OSA after treatment for AF. Second, it will identify the possible
      pathophysiologic mechanisms for this association. In doing so, it will discuss
      the investigated effects of intrathoracic pressure changes, autonomic instability
      and atrial remodeling. Finally, it will review the evidence of the effect of
      treatment of OSA on AF, highlighting the role of continuous positive airway
      pressure (CPAP) in the treatment of OSA and its impact on AF prevalence and
      recurrence.

PMID- 23003205
TI  - Strain-dependent effects of inoculation of Lactobacillus plantarum subsp.
      plantarum on fermentation quality of paddy rice (Oryza sativa L. subsp. japonica)
      silage.
AB  - Paddy rice has been of particular interest as a forage crop in Japan. In this
      study, the isolated strains TO1000, TO1001, TO1002, and TO1003 were characterized
      by phenotypic and genotypic approaches. These strains were identified as
      Lactobacillus plantarum subsp. plantarum by species-specific PCR. Phenotypic
      characteristics varied among different strains of the same subspecies, and the
      strains represented unique and diverse phenotypes related to fermentation
      factors, such as carbohydrate assimilation and range of pH and temperature
      allowing growth. PCR analysis revealed that the patterns of presence/absence of
      known plantaricin genes differed in a strain-specific manner. Using these strains
      as inoculants for preparation of whole crop paddy rice silage, fermentation
      quality was significantly improved, as shown by lower pH, higher lactic acid
      content, and inhibition of the growth of undesirable microorganisms such as
      molds, coliform bacteria, and clostridia, after 30 and 60 days of storage, with
      effectiveness differing from strain to strain. These observations suggest that
      suitable candidates for bacterial inoculants in silage preparation should be
      screened at the strain level. Strain TO1002 may be useful for producing silage
      inoculants for the production of well-preserved whole crop paddy rice silage.

PMID- 23003206
TI  - Oncological and functional outcomes after radical nephrectomy for renal cell
      carcinoma: a comprehensive analysis of prognostic factors.
AB  - OBJECTIVES: To investigate mortality rates and to comprehensively analyze
      prognostic indicators after radical nephrectomy for renal cell carcinoma.
      METHODS: Data were collected from 147 patients who underwent potentially curative
      radical nephrectomy for renal cell carcinoma. The following data were analyzed:
      tumor pathology, patient demographics and clinical parameters, such as pre- and
      postoperative estimated glomerular filtration rate, as well as the cause of
      death. Cause-specific survival rates were calculated including deaths caused by
      renal cell carcinoma and cardiovascular disease. A Cox proportional hazard model
      was used for statistical analysis. RESULTS: A univariate analysis showed that age
      at surgery (>=70 years), postoperative estimated glomerular filtration rate (<45
      mL/min/1.73 m(2)), pathological high T stage, grade and venous invasion were
      significant poor prognostic indicators. The multivariate analysis provided
      evidence that pathological venous invasion was a significant poor prognostic
      indicator, whereas age at surgery (>=70 years), pre- (<65 mL/min/1.73 m(2)) or
      postoperative (<45 mL/min/1.73 m(2)) estimated glomerular filtration rate and
      pathological high grade were significant poor prognostic indicators in T1 tumor
      cases. CONCLUSIONS: Post-radical nephrectomy renal function insufficiency can
      lead to a poor prognostic outcome, especially in patients with T1 renal cell
      carcinoma. Physicians should consider a comprehensive follow up focusing on
      possible causes of death, including those related to both renal cell carcinoma
      and cardiovascular disease events after radical nephrectomy.

PMID- 23003207
TI  - Surreptitious antiretroviral use as an explanation for apparent elite HIV
      control.

PMID- 23003208
TI  - What is the 'dark figure' of child homicide and how can it be addressed in
      Australia?
AB  - Child injury, regardless of intent, is a major public health issue in Australia
      and elsewhere. Child protection and injury prevention policies and practices are
      implemented in most countries in an attempt to manage and reduce the incidence of
      both intentional and unintentional injuries. While these systems are thought to
      assist in improving protection from violence, injury and neglect, one of the
      major limitations in understanding the effectiveness of child protection policy
      in Australia is a lack of reliable national data on child abuse and neglect. As a
      result there is a lack of an appropriate evidence base on which to guide the
      development of effective policies. A particular area where official figures may
      under-represent the true prevalence of child deaths is those which result from
      homicide. This article provides a review of the recent literature on child
      homicide, abuse and neglect, with the overall aim of understanding more fully the
      reasons for the possible under-representation of child homicides and provides
      recommendations to address this problem in Australia. Improvements in methods of
      identifying at risk children in addition to systematic investigations of child
      deaths to understand the risk factors and underlying contributing factors are
      required. 

PMID- 23003209
TI  - Effective salvage of acute massive uterine bleeding using intrauterine balloon
      tamponade in a uterine adenomyosis patient on dienogest.
AB  - We present the case of a 37-year-old nulliparous woman in whom acute massive
      uterine bleeding during dienogest therapy was successfully treated using
      intrauterine balloon tamponade. Abnormal uterine bleeding and several cases of
      profuse bleeding causing severe anemia in association with dienogest therapy have
      been reported, but this is the first reported case involving hypovolemic shock.
      While successful control of postpartum hemorrhage with intrauterine balloon
      tamponade has been well described, applications for non-obstetric bleeding,
      particularly in the presence of underlying diseases, such as adenomyosis, have
      only rarely been reported. This procedure can be easily, promptly, and safely
      implemented without analgesia, anesthesia, or laparotomy; it can be used with a
      minimally dilated external cervical os or narrow uterine cavity; and it can
      preserve fertility.

PMID- 23003210
TI  - Development of an agricultural biotechnology crop product: testing from discovery
      to commercialization.
AB  - "Genetically modified" (GM) or "biotech" crops have been the most rapidly adopted
      agricultural technology in recent years. The development of a GM crop encompasses
      trait identification, gene isolation, plant cell transformation, plant
      regeneration, efficacy evaluation, commercial event identification, safety
      evaluation, and finally commercial authorization. This is a lengthy, complex, and
      resource-intensive process. Crops produced through biotechnology are the most
      highly studied food or food component consumed. Before commercialization, these
      products are shown to be as safe as conventional crops with respect to feed,
      food, and the environment. This paper describes this global process and the
      various analytical tests that must accompany the product during the course of
      development, throughout its market life, and beyond.

PMID- 23003211
TI  - A comparison of the pelvic angle applied using lateral table tilt or a pelvic
      wedge at elective caesarean section.
AB  - Lateral table tilt or a pelvic wedge are commonly used to reduce inferior vena
      cava compression during obstetric anaesthesia in the supine position. Direct
      measurement of pelvic angle allows individual assessment of the effectiveness of
      these manoeuvres in achieving a tilted position. We observed routine practice
      during caesarean section after random allocation to one or other of these
      methods. The anaesthetist managing the case was asked to position the women after
      induction of spinal anaesthesia using either left table tilt or a wedge under the
      right hip. We then measured pelvic angle in all women, and the table angle in
      women who had table tilt. The mean (SD [range]) pelvic angle was 20.2 degrees 
      (8.1 degrees  [9 degrees -37 degrees ]) in 18 women with table tilt and 21.0
      degrees  (7.5 degrees  [10 degrees -36 degrees ]) in 17 women with a wedge. The
      mean (SD [range]) table angle was 12.4 degrees  (3.1 degrees  [8 degrees -21
      degrees ]) in the women with table tilt. There was a significant difference
      between table angle and pelvic angle in the women with table tilt (p = 0.0003),
      but no significant difference in pelvic angle between the table tilt and wedge
      groups. Measurement of table angle does not represent pelvic position adequately
      in the majority of women. However, this study showed that lateral table tilt and
      a pelvic wedge were equally effective in producing tilt of the pelvis.

PMID- 23003213
TI  - Effect of surfactant and solvent on spin-lattice relaxation dynamics of magnetic
      nanocrystals.
AB  - The effect of varying the surfactant and solvent medium on the dynamics of spin
      lattice relaxation in photoexcited Fe3O4 nanocrystals has been investigated by
      measuring the time-dependent magnetization employing pump-probe transient Faraday
      rotation technique. The variation of the surfactants having surface-binding
      functional groups modified not only the static magnetization but also the
      dynamics of the recovery of the magnetization occurring via spin-lattice
      relaxation in the photoexcited Fe3O4 nanocrystals. The variation of the polarity
      and size of the solvent molecules can also influence the spin-lattice relaxation
      dynamics. However, the effect is limited to the nanocrystals having sufficiently
      permeable surfactant layer, where the small solvent molecules (e.g., water) can
      access the surface and dynamically modify the ligand field on the surface.

PMID- 23003212
TI  - The circadian clock machinery during early development of Senegalese sole (Solea
      senegalensis): effects of constant light and dark conditions.
AB  - Circadian rhythms are established very early during vertebrate development. In
      fish, environmental cues can influence the initiation and synchronization of
      different rhythmic processes. Previous studies in zebrafish and rainbow trout
      have shown that circadian oscillation of clock genes represents one of the
      earliest detectable rhythms in the developing embryo, suggesting their
      significance in regulating the coordination of developmental processes. In this
      study, we analyzed the daily expression of the core clock components Per1, Per2,
      Per3, and Clock during the first several days of Senegalese sole development (0-4
      d post fertilization or dpf) under different lighting regimes, with the aim of
      addressing when the molecular clock first emerges in this species and how it is
      affected by different photoperiods. Rhythmic expression of the above genes was
      detected from 0 to 1 dpf, being markedly affected in the next few days by both
      constant light (LL) and dark (DD) conditions. A gradual entrainment of the clock
      machinery was observed only under light-dark (LD) cycles, and robust rhythms with
      increased amplitudes were established by 4 dpf for all clock genes currently
      studied. Our results show the existence of an embryonic molecular clock from the
      1st d of development in Senegalese sole and emphasize the significance of cycling
      LD conditions when raising embryos and early larvae.

PMID- 23003214
TI  - Bulk superconductivity in bismuth oxysulfide Bi4O4S3.
AB  - A very recent report on the observation of superconductivity in Bi(4)O(4)S(3)
      [Mizuguchi, Y.; http://arxiv.org/abs/1207.3145] could potentially reignite the
      search for superconductivity in a broad range of layered sulfides. We report here
      the synthesis of Bi(4)O(4)S(3) at 500  degrees C by a vacuum encapsulation
      technique and its basic characterizations. The as-synthesized Bi(4)O(4)S(3) was
      contaminated with small amounts of Bi(2)S(3) and Bi impurities. The majority
      phase was found to be tetragonal (space group I4/mmm) with lattice parameters a =
      3.9697(2) A and c = 41.3520(1) A. Both AC and DC magnetization measurements
      confirmed that Bi(4)O(4)S(3) is a bulk superconductor with a superconducting
      transition temperature (T(c)) of 4.4 K. Isothermal magnetization (M-H)
      measurements indicated closed loops with clear signatures of flux pinning and
      irreversible behavior. The lower critical field (H(c1)) at 2 K for the new
      superconductor was found to be ~15 Oe. Magnetotransport measurements showed a
      broadening of the resistivity (rho) and a decrease in T(c) (rho = 0) with
      increasing magnetic field. The extrapolated upper critical field H(c2)(0) was ~31
      kOe with a corresponding Ginzburg-Landau coherence length of ~100 A . In the
      normal state, the rho ~ T(2) dependence was not indicated. Hall resistivity data
      showed a nonlinear magnetic field dependence. Our magnetization and electrical
      transport measurements substantiate the appearance of bulk superconductivity in
      as-synthesized Bi(4)O(4)S(3). On the other hand, Bi heat-treated at the same
      temperature is not superconducting, thus excluding the possibility of impurity
      driven superconductivity in the newly discovered superconductor Bi(4)O(4)S(3).

PMID- 23003215
TI  - Social host policies and underage drinking parties.
AB  - Social host policies focused on underage drinking parties are implemented to
      reduce social availability of alcohol and high-risk drinking by adolescents in
      private locations. We examined the policies' relationship with drinking location,
      peer-group drinking size, heavy episodic drinking, and nonviolent consequences.
      Cross-sectional data from 11,205, 14-20-year olds, were analyzed using multilevel
      modeling. Policies were not associated with drinking location, decreased heavy
      episodic drinking, or nonviolent consequences. However, adolescents from
      communities with a preexisting policy had lower odds of drinking in large peer
      groups compared to those from communities without a policy at baseline.
      Additional research is needed to examine their effectiveness. The study's
      limitations are noted.

PMID- 23003216
TI  - Phast4Windows: a 3D graphical user interface for the reactive-transport simulator
      PHAST.
AB  - Phast4Windows is a Windows(r) program for developing and running groundwater-flow
      and reactive-transport models with the PHAST simulator. This graphical user
      interface allows definition of grid-independent spatial distributions of model
      properties-the porous media properties, the initial head and chemistry
      conditions, boundary conditions, and locations of wells, rivers, drains, and
      accounting zones-and other parameters necessary for a simulation. Spatial data
      can be defined without reference to a grid by drawing, by point-by-point
      definitions, or by importing files, including ArcInfo(r) shape and raster files.
      All definitions can be inspected, edited, deleted, moved, copied, and switched
      from hidden to visible through the data tree of the interface. Model features are
      visualized in the main panel of the interface, so that it is possible to zoom,
      pan, and rotate features in three dimensions (3D). PHAST simulates single phase,
      constant density, saturated groundwater flow under confined or unconfined
      conditions. Reactions among multiple solutes include mineral equilibria, cation
      exchange, surface complexation, solid solutions, and general kinetic reactions.
      The interface can be used to develop and run simple or complex models, and is
      ideal for use in the classroom, for analysis of laboratory column experiments,
      and for development of field-scale simulations of geochemical processes and
      contaminant transport. 

PMID- 23003217
TI  - Effects of weighting schemes on the identification of wildlife corridors
      generated with least-cost methods.
AB  - The importance of movement corridors for maintaining connectivity within
      metapopulations of wild animals is a cornerstone of conservation. One common
      approach for determining corridor locations is least-cost corridor (LCC)
      modeling, which uses algorithms within a geographic information system to search
      for routes with the lowest cumulative resistance between target locations on a
      landscape. However, the presentation of multiple LCCs that connect multiple
      locations generally assumes all corridors contribute equally to connectivity,
      regardless of the likelihood that animals will use them. Thus, LCCs may
      overemphasize seldom-used longer routes and underemphasize more frequently used
      shorter routes. We hypothesize that, depending on conservation objectives and
      available biological information, weighting individual corridors on the basis of
      species-specific movement, dispersal, or gene flow data may better identify
      effective corridors. We tested whether locations of key connectivity areas,
      defined as the highest 75th and 90th percentile cumulative weighted value of
      approximately 155,000 corridors, shift under different weighting scenarios. In
      addition, we quantified the amount and location of private land that intersect
      key connectivity areas under each weighting scheme. Some areas that appeared well
      connected when analyzed with unweighted corridors exhibited much less
      connectivity compared with weighting schemes that discount corridors with large
      effective distances. Furthermore, the amount and location of key connectivity
      areas that intersected private land varied among weighting schemes. We believe
      biological assumptions and conservation objectives should be explicitly
      incorporated to weight corridors when assessing landscape connectivity. These
      results are highly relevant to conservation planning because on the basis of
      recent interest by government agencies and nongovernmental organizations in
      maintaining and enhancing wildlife corridors, connectivity will likely be an
      important criterion for prioritization of land purchases and swaps.

PMID- 23003218
TI  - Care priorities- Registered Nurses' clinical daily work in municipal elderly care
      settings.
AB  - Common in Swedish elderly home care is that Registered Nurses work independently,
      and lead the care team without being a part of it. People involved in the care of
      the patient can be social services, physician, Registered Nurse (RN), nurses in
      inpatient care and family. In according to current model for nursing
      documentation RNs interventions is described as participation,
      information/education, support, environment, general care, training,
      observation/surveillance, special care drug administration and coordination. Time
      pressure is perceived as high, but the nurses have the opportunity to influence
      their daily work situation and make priorities. The purpose of this study was to
      investigate how RNs prioritise interventions in municipal elderly care settings.
      A quantitative descriptive method was used for the study. Data were collected
      during the months of April and October 2004 - 2008, using a web-based form. The
      nurses filled in patient's type of housing, performed interventions, and if the
      interventions were delegated. Interventions were described as keywords and were
      attributed a certain amount of time, calculated in previous time studies. The
      inclusion criteria were: all patients 80 years of age and older, in a
      municipality in south-western Sweden, who received some form of health care from
      a RN, or performed by non-certified staff by delegation. Results indicate that
      differences in priority could be observed, depending on the patient's gender, or
      whether the patient was living in independent or sheltered housing. Drug
      administration was prioritised for female patients, while coordination became a
      priority for patients living in ordinary housing. Support received the highest
      priority, regardless if the patient lived in ordinary or sheltered housing.
      However, it is not entirely clear what support signifies in municipal health care
      settings, and this issue would therefore require further investigation.

PMID- 23003219
TI  - Is handedness related to anxiety? New answers to an old question.
AB  - Is handedness related to anxiety? Two separable dimensions of handedness have
      been considered in previous studies: Direction of the preferred hand (left or
      right) and the consistency with which the preferred hand is used over the
      nonpreferred hand (consistent or inconsistent). Findings have included (1) left
      handedness being associated with greater anxiety than right-handedness, (2)
      consistent-handedness being associated with greater anxiety than inconsistent
      handedness and (3) neither dimension being associated with anxiety. Here, we
      administered measures of trait anxiety, state anxiety and worry to individuals
      classified as consistent-left, inconsistent-left, inconsistent-right or
      consistent-right. Neither direction nor consistency had a main effect on any
      measure. However, there was a direction by consistency interaction in trait and
      state anxiety measured on the State/Trait Anxiety Inventory. Among right-handers,
      inconsistent individuals reported less anxiety than consistent individuals. Among
      left-handers, consistency was unrelated to anxiety. In consequence of this
      pattern, inconsistent right-handers were less anxious than inconsistent left
      handers. Hence, supporting prior studies, left-handedness was associated with
      greater anxiety than right-handedness (but only among inconsistent individuals)
      and consistency was associated with greater anxiety than inconsistency (but only
      among right-handers). These findings advance our understanding of handedness
      consistency as an important individual difference factor in personality and
      cognition. 

PMID- 23003220
TI  - Prevalence and extent of subclinical atherosclerosis in patients with psoriasis.
AB  - OBJECTIVE: Patients with psoriasis are prone to premature atherosclerosis and
      increased risk of cardiovascular disease events. However, the prevalence and
      extent of atherosclerosis in patients with psoriasis are unknown. DESIGN: A cross
      sectional study. SETTING AND SUBJECTS: The prevalence and extent of coronary and
      carotid atherosclerosis were compared in 70 patients with psoriasis (46 +/- 9
      years, 71% male) without known cardiovascular disease or joint involvement and 51
      age- and gender-matched healthy control subjects (45 +/- 7 years, 71% male).
      Systemic inflammation was assessed by the level of high-sensitivity C-reactive
      protein (hs-CRP). Coronary atherosclerosis was determined by the coronary
      calcification score (CCS) measured by multi-detector computed tomography. Carotid
      atherosclerosis was assessed by high-resolution ultrasound-derived carotid intima
      media thickness (cIMT). RESULTS: Patients with psoriasis had a higher prevalence
      of coronary atherosclerosis (CCS > 0; 28.6% vs. 3.9%, P < 0.01), and a higher
      degree of coronary atherosclerosis estimated by the mean CCS (67.4 +/- 349.2 vs.
      0.5 +/- 3.0, P < 0.05) compared with controls. Similarly, cIMT was significantly
      greater in patients with psoriasis than in control subjects (0.73 +/- 0.11 mm vs.
      0.67 +/- 0.08 mm, P < 0.01). Multiple logistic regression revealed that psoriasis
      [odd ratio (OR): 10.54, 95% confidence interval (CI) 1.89-58.67, P < 0.01] and
      serum total cholesterol level (OR 2.10, 95% CI 1.01-4.37) were associated with
      the presence of coronary atherosclerosis (CCS > 0). By contrast, only age was
      independently associated with increased cIMT. Amongst participants with no
      traditional cardiovascular disease risk factors, hs-CRP level was higher in
      patients with psoriasis than in controls. CONCLUSION: The present results
      demonstrate early-onset, diffuse arterial atherosclerosis in coronary and carotid
      arteries in patients with psoriasis, but not in age- and gender-matched control
      subjects. Low-grade inflammation could explain the presence of premature
      atherosclerosis in patients with psoriasis.

PMID- 23003221
TI  - Bose-Einstein condensation of erbium.
AB  - We report on the achievement of Bose-Einstein condensation of erbium atoms and on
      the observation of magnetic Feshbach resonances at low magnetic fields. By means
      of evaporative cooling in an optical dipole trap, we produce pure condensates of
      168Er, containing up to 7*10(4) atoms. Feshbach spectroscopy reveals an
      extraordinary rich loss spectrum with six loss resonances already in a narrow
      magnetic-field range up to 3 G. Finally, we demonstrate the application of a low
      field Feshbach resonance to produce a tunable dipolar Bose-Einstein condensate
      and we observe its characteristic d-wave collapse.

PMID- 23003222
TI  - Nonlocal memory effects in the dynamics of open quantum systems.
AB  - We explore the possibility to generate nonlocal dynamical maps of an open quantum
      system through local system-environment interactions. Employing a generic
      decoherence process induced by a local interaction Hamiltonian, we show that
      initial correlations in a composite environment can lead to nonlocal open system
      dynamics which exhibit strong memory effects, although the local dynamics is
      Markovian. In a model of two entangled photons interacting with two dephasing
      environments, we find a direct connection between the degree of memory effects
      and the amount of correlation in the initial environmental state. The results
      demonstrate that, contrary to conventional wisdom, enlarging an open system can
      change the dynamics from Markovian to non-Markovian.

PMID- 23003223
TI  - Macroscopic tunneling of a membrane in an optomechanical double-well potential.
AB  - The macroscopic tunneling of an optomechanical membrane is considered. A cavity
      mode which couples quadratically to the membranes position can create highly
      tunable adiabatic double-well potentials, which together with the high Q factors
      of such membranes render the observation of macroscopic tunneling possible. A
      suitable, pulsed measurement scheme using a linearly coupled mode of the cavity
      for the verification of the effect is studied.

PMID- 23003224
TI  - Sub-Heisenberg estimation strategies are ineffective.
AB  - In interferometry, sub-Heisenberg strategies claim to achieve a phase estimation
      error smaller than the inverse of the mean number of photons employed (Heisenberg
      bound). Here we show that one can achieve a comparable precision without
      performing any measurement, just using the large prior information that sub
      Heisenberg strategies require. For uniform prior (i.e., no prior information), we
      prove that these strategies cannot achieve more than a fixed gain of about 1.73
      over Heisenberg-limited interferometry. Analogous results hold for arbitrary
      single-mode prior distributions. These results extend also beyond interferometry:
      the effective error in estimating any parameter is lower bounded by a quantity
      proportional to the inverse expectation value (above a ground state) of the
      generator of translations of the parameter.

PMID- 23003225
TI  - Uncertainty relations from simple entropic properties.
AB  - Uncertainty relations provide constraints on how well the outcomes of
      incompatible measurements can be predicted, and as well as being fundamental to
      our understanding of quantum theory, they have practical applications such as for
      cryptography and witnessing entanglement. Here we shed new light on the entropic
      form of these relations, showing that they follow from a few simple properties,
      including the data-processing inequality. We prove these relations without
      relying on the exact expression for the entropy, and hence show that a single
      technique applies to several entropic quantities, including the von Neumann
      entropy, min- and max-entropies, and the Renyi entropies.

PMID- 23003226
TI  - Association of Efimov trimers from a three-atom continuum.
AB  - We develop an experimental technique for rf association of Efimov trimers from a
      three-atom continuum. We apply it to probe the lowest accessible Efimov energy
      level in bosonic lithium in the region where strong deviations from the universal
      behavior are expected, and provide a quantitative study of this effect. The
      position of the Efimov resonance at the atom-dimer threshold, measured using a
      different experimental technique, concurs with the rf association results.

PMID- 23003227
TI  - Nonlocality of symmetric states.
AB  - In this Letter we study the nonlocal properties of permutation symmetric states
      of n qubits. We show that all these states are nonlocal, via an extended version
      of the Hardy paradox and associated inequalities. Natural extensions of both the
      paradoxes and the inequalities are developed which relate different entanglement
      classes to different nonlocal features. Belonging to a given entanglement class
      will guarantee the violation of associated Bell inequalities which see the
      persistence of correlations to subsets of players, whereas there are states
      outside that class which do not violate.

PMID- 23003228
TI  - Holographic storage of biphoton entanglement.
AB  - Coherent and reversible storage of multiphoton entanglement with a multimode
      quantum memory is essential for scalable all-optical quantum information
      processing. Although a single photon has been successfully stored in different
      quantum systems, storage of multiphoton entanglement remains challenging because
      of the critical requirement for coherent control of the photonic entanglement
      source, multimode quantum memory, and quantum interface between them. Here we
      demonstrate a coherent and reversible storage of biphoton Bell-type entanglement
      with a holographic multimode atomic-ensemble-based quantum memory. The retrieved
      biphoton entanglement violates the Bell inequality for 1 MUs storage time and a
      memory-process fidelity of 98% is demonstrated by quantum state tomography.

PMID- 23003229
TI  - Stochastic energetics for non-Gaussian processes.
AB  - By introducing a new stochastic integral, we investigate the energetics of
      classical stochastic systems driven by non-Gaussian white noises. In particular,
      we introduce a decomposition of the total energy difference into the work and the
      heat for each trajectory, and derive a formula to calculate the heat from
      experimental data on the dynamics. We apply our formulation and results to a
      Langevin system driven by a Poisson noise.

PMID- 23003230
TI  - Efficiency of isothermal molecular machines at maximum power.
AB  - We derive upper and lower bounds for the efficiency of an isothermal molecular
      machine operating at maximum power. The upper bound is reached when the activated
      state is close to the fueling or reactant state (Eyring-like), while the lower
      bound is reached when the activated state is close to the product state (Kramers
      like).

PMID- 23003231
TI  - Geometric heat flux for classical thermal transport in interacting open systems.
AB  - We study classical heat conduction in a dissipative open system composed of
      interacting oscillators. By exactly solving a twisted Fokker-Planck equation
      which describes the full counting statistics of heat flux flowing through the
      system, we identify the geometric-phase-like effect and examine its impact on the
      classical heat transport. We find that the nonlinear interaction as well as the
      closely related temperature dependence of system parameters are crucial in
      manifesting the geometric-phase contribution of heat flux. Finally, we propose an
      electronic experiment based on RC circuits to verify our theoretical predictions.

PMID- 23003232
TI  - Fluctuation theorems for an asymmetric rotor in a granular gas.
AB  - We investigate the validity of fluctuation theorems for an asymmetric rotor
      experiment in a granular gas. A first state, with a Gaussian distribution of the
      angular velocity, is found to be well described by a first order Langevin
      equation. We show that fluctuation theorems are valid for the injected work and
      for the total entropy production. In a second state, the angular velocity
      distribution is double peaked due to a spontaneous symmetry breaking: A
      convection roll develops in the granular gas, which strongly couples to the
      rotor. Surprisingly, in this case, similar symmetry relations hold, which lead to
      a good prediction for the height ratio of the two peaks.

PMID- 23003233
TI  - Quantum isoperiodic stable structures and directed transport.
AB  - It has been recently found that the so-called isoperiodic stable structures
      (ISSs) have a fundamental role in the classical current behavior of dissipative
      ratchets [Phys. Rev. Lett. 106, 234101 (2011).]. Here I analyze their quantum
      counterparts, the quantum ISSs (QISSs), which have a fundamental role in the
      quantum current behavior. QISSs have the simple attractor shape of those ISSs
      which settle down in short times. However, in the majority of the cases they are
      strongly different from the ISSs, looking approximately the same as the quantum
      chaotic attractors that are at their vicinity in parameter space. By adding
      thermal fluctuations of the size of h(eff) to the ISSs I am able to obtain very
      good approximations to the QISSs. I conjecture that in general, quantum chaotic
      attractors could be well approximated by means of just the classical information
      of a neighboring ISS plus thermal fluctuations. I expect to find this behavior in
      quantum dissipative systems in general.

PMID- 23003234
TI  - Cavity-enhanced parity-nonconserving optical rotation in metastable Xe and Hg.
AB  - We propose the measurement of cavity-enhanced parity-nonconserving (PNC) optical
      rotation in several transitions of metastable Xe and Hg, including Xe
      (2P(3/2)(o))6s(2)[3/2](2)(o)->(2P(1/2)(o))6s(2)[1/2](1)(o) and Hg 6s6p (3)P(2)(o)
      >6s6p (1)P(1)(o), with calculated amplitude ratios of E(1)(PNC)/M1=11*10(-8) and
      10*10(-8), respectively. We demonstrate the use of a high-finesse bow-tie cavity
      with counterpropagating beams and a longitudinal magnetic field, which allows the
      absolute measurement of chiral optical rotation, with a path length enhancement
      of about 10(4), necessary for PNC measurement from available column densities of
      10(14) cm(-2) for metastable Xe or Hg. Rapid PNC-signal reversal, allowing robust
      background subtraction, is achieved by shifting the cavity resonance to an
      opposite polarization mode or by inverting the magnetic field. The precise
      measurement of isotope and nuclear-spin dependent E(1)(PNC) amplitudes provides a
      sensitive low-energy test of the standard model.

PMID- 23003235
TI  - Comparison of atom interferometers and light interferometers as space-based
      gravitational wave detectors.
AB  - We consider a class of proposed gravitational-wave detectors based on multiple
      atomic interferometers separated by large baselines and referenced by common
      laser systems. We compute the sensitivity limits of these detectors due to
      intrinsic phase noise of the light sources, noninertial motion of the light
      sources, and atomic shot noise and compare them to sensitivity limits for
      traditional light interferometers. We find that atom interferometers and light
      interferometers are limited in a nearly identical way by intrinsic phase noise
      and that both require similar mitigation strategies (e.g., multiple-arm
      instruments) to reach interesting sensitivities. The sensitivity limit from
      motion of the light sources is slightly different and, in principle, favors the
      atom interferometers in the low-frequency limit, although the limit in both cases
      is severe.

PMID- 23003236
TI  - Common solution to the cosmic ray anisotropy and gradient problems.
AB  - Multichannel cosmic ray spectra and the large scale cosmic ray anisotropy can
      hardly be made compatible in the framework of conventional isotropic and
      homogeneous propagation models. These models also have problems explaining the
      longitude distribution and the radial emissivity gradient of the gamma-ray
      Galactic interstellar emission. We argue here that accounting for a physically
      motivated correlation between the cosmic ray escape time and the spatially
      dependent magnetic turbulence power can naturally solve both problems. Indeed, by
      exploiting this correlation we find propagation models that fit a wide set of
      cosmic ray spectra, and consistently reproduce the cosmic ray anisotropy in the
      energy range 10(2)-10(4) GeV and the gamma-ray longitude distribution recently
      measured by Fermi-LAT.

PMID- 23003237
TI  - Lensing of 21-cm fluctuations by primordial gravitational waves.
AB  - Weak-gravitational-lensing distortions to the intensity pattern of 21-cm
      radiation from the dark ages can be decomposed geometrically into curl and curl
      free components. Lensing by primordial gravitational waves induces a curl
      component, while the contribution from lensing by density fluctuations is
      strongly suppressed. Angular fluctuations in the 21-cm background extend to very
      small angular scales, and measurements at different frequencies probe different
      shells in redshift space. There is thus a huge trove of information with which to
      reconstruct the curl component of the lensing field, allowing tensor-to-scalar
      ratios conceivably as small as r~10(-9)-far smaller than those currently
      accessible-to be probed.

PMID- 23003238
TI  - Helical superconducting black holes.
AB  - We construct novel static, asymptotically five-dimensional anti-de Sitter black
      hole solutions with Bianchi type-VII(0) symmetry that are holographically dual to
      superconducting phases in four spacetime dimensions with a helical p-wave order.
      We calculate the precise temperature dependence of the pitch of the helical
      order. At zero temperature the black holes have a vanishing entropy and approach
      domain wall solutions that reveal homogenous, nonisotropic dual ground states
      with an emergent scaling symmetry.

PMID- 23003239
TI  - Search for low-mass dark-sector Higgs bosons.
AB  - Recent astrophysical and terrestrial experiments have motivated the proposal of a
      dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We
      present a search for a dark Higgs boson using 516 fb(-1) of data collected with
      the BABAR detector. We do not observe a significant signal and we set 90%
      confidence level upper limits on the product of the standard model-dark-sector
      mixing angle and the dark-sector coupling constant.

PMID- 23003241
TI  - Evidence for the charmless annihilation decay mode B(s)(0)->pi(+)pi(-).
AB  - We search for annihilation decay modes of neutral b mesons into pairs of
      charmless charged hadrons with the upgraded Collider Detector at the Fermilab
      Tevatron. Using a data sample corresponding to 6 fb(-1) of integrated luminosity,
      we obtain the first evidence for the B(s)(0)->pi(+)pi(-) decay, with a
      significance of 3.7sigma, and a measured branching ratio B(B(s)(0)->pi(+)pi(
      ))=(0.57+/-0.15(stat)+/-0.10(syst))*10(-6). A search for the B(0)->K(+)K(-) mode
      in the same sample yields a significance of 2.0sigma, and a central value
      estimate B(B(0)->K(+)K(-))=(0.23+/-0.10(stat)+/-0.10(syst))*10(-6).

PMID- 23003242
TI  - Search for dark matter in events with one jet and missing transverse energy in pp
      collisions at ?s=1.96 TeV.
AB  - We present the results of a search for dark matter production in the monojet
      signature. We analyze a sample of Tevatron pp[over -] collisions at ?s=1.96 TeV
      corresponding to an integrated luminosity of 6.7 fb(-1) recorded by the CDF II
      detector. In events with large missing transverse energy and one energetic jet,
      we find good agreement between the standard model prediction and the observed
      data. We set 90% confidence level upper limits on the dark matter production
      rate. The limits are translated into bounds on nucleon-dark matter scattering
      rates which are competitive with current direct detection bounds on spin
      independent interaction below a dark matter candidate mass of 5 GeV/c(2), and on
      spin-dependent interactions up to masses of 200 GeV/c(2).

PMID- 23003246
TI  - Elucidation of the anomalous A=9 isospin quartet behavior.
AB  - Recent high-precision mass measurements of 9Li and 9Be, performed with the TITAN
      Penning trap at the TRIUMF ISAC facility, are analyzed in light of state-of-the
      art shell model calculations. We find an explanation for the anomalous isobaric
      mass multiplet equation behavior for the two A=9 quartets. The presence of a
      cubic d=6.3(17) keV term for the J(pi)=3/2(-) quartet and the vanishing cubic
      term for the excited J(pi)=1/2(-) multiplet depend upon the presence of a nearby
      T=1/2 state in 9B and 9Be that induces isospin mixing. This is contrary to
      previous hypotheses involving purely Coulomb and charge-dependent effects. T=1/2
      states have been observed near the calculated energy, above the T=3/2 state.
      However, an experimental confirmation of their J(pi) is needed.

PMID- 23003250
TI  - Nonadiabatic forces in ion-solid interactions: the initial stages of radiation
      damage.
AB  - The Born-Oppenheimer approximation is the keystone for molecular dynamics
      simulations of radiation damage processes; however, actual materials response
      involves nonadiabatic energy exchange between nuclei and electrons. In this work,
      time dependent density functional theory is used to calculate the electronic
      excitations produced by energetic protons in Al. We study the influence of these
      electronic excitations on the interatomic forces and find that they differ
      substantially from the adiabatic case, revealing a nontrivial connection between
      electronic and nuclear stopping that is absent in the adiabatic case. These
      results unveil new effects in the early stages of radiation damage cascades.

PMID- 23003249
TI  - Spectroscopy and thermometry of drumhead modes in a mesoscopic trapped-ion
      crystal using entanglement.
AB  - We demonstrate spectroscopy and thermometry of individual motional modes in a
      mesoscopic 2D ion array using entanglement-induced decoherence as a method of
      transduction. Our system is a ~400 MUm-diameter planar crystal of several hundred
      9Be(+) ions exhibiting complex drumhead modes in the confining potential of a
      Penning trap. Exploiting precise control over the 9Be(+) valence electron spins,
      we apply a homogeneous spin-dependent optical dipole force to excite arbitrary
      transverse modes with an effective wavelength approaching the interparticle
      spacing (~20 MUm). Center-of-mass displacements below 1 nm are detected via the
      entanglement of spin and motional degrees of freedom.

PMID- 23003245
TI  - Identifying the charge carriers of the quark-gluon plasma.
AB  - Charge correlations in lattice gauge calculations suggest that up, down, and
      strange charges move independently in the quark-gluon plasma, and that the
      density of such charges is similar to what is expected from simple thermal
      arguments. Here, we show how specific elements of the charge-charge correlation
      matrix in the quark-gluon plasma survive hadronization and become manifest in
      final-state charge-charge correlation measurements.

PMID- 23003243
TI  - Search for a heavy particle decaying to a top quark and a light quark in pp -
      collisions at ?s=1.96 TeV.
AB  - We present a search for a new heavy particle X produced in association with a top
      quark, pp[over -]->t(X->t[over -]q) or pp[over -]->t[over -](X[over -]->tq[over 
      ]), where q stands for up quarks and down quarks. Such a particle may explain the
      recent anomalous measurements of top-quark forward-backward asymmetry. If the
      light-flavor quark (q) is reconstructed as a jet (j), this gives a t[over -]+j or
      t+j resonance in tt[over -]+jet events, a previously unexplored experimental
      signature. In a sample of events with exactly one lepton, missing transverse
      momentum and at least five jets, corresponding to an integrated luminosity of 8.7
      fb(-1) collected by the CDF II detector, we find the data to be consistent with
      the standard model. We set cross-section upper limits on the production (pp[over 
      ]->Xt or X[over -]t[over -]) at 95% confidence level from 0.61 pb to 0.02 pb for
      X masses ranging from 200 GeV/c(2) to 800 GeV/c(2), respectively.

PMID- 23003247
TI  - Variational two-particle density matrix calculation for the Hubbard model below
      half filling using spin-adapted lifting conditions.
AB  - The variational determination of the two-particle density matrix is an
      interesting, but not yet fully explored technique that allows us to obtain ground
      state properties of a quantum many-body system without reference to an N-particle
      wave function. The one-dimensional fermionic Hubbard model has been studied
      before with this method, using standard two- and three-index conditions on the
      density matrix [J. R. Hammond et al., Phys. Rev. A 73, 062505 (2006)], while a
      more recent study explored so-called subsystem constraints [N. Shenvi et al.,
      Phys. Rev. Lett. 105, 213003 (2010)]. These studies reported good results even
      with only standard two-index conditions, but have always been limited to the half
      filled lattice. In this Letter, we establish the fact that the two-index approach
      fails for other fillings. In this case, a subset of three-index conditions is
      absolutely needed to describe the correct physics in the strong-repulsion limit.
      We show that applying lifting conditions [J. R. Hammond et al., Phys. Rev. A 71,
      062503 (2005)] is the most economical way to achieve this, while still avoiding
      the computationally much heavier three-index conditions. A further extension to
      spin-adapted lifting conditions leads to increased accuracy in the intermediate
      repulsion regime. At the same time, we establish the feasibility of such studies
      to the more complicated phase diagram in two-dimensional Hubbard models.

PMID- 23003251
TI  - New class of three-body states.
AB  - We calculate the three-body spectrum for identical bosons interacting via
      attractive 1/r(2) potentials. We find an infinite number of three-body states
      even when the pair interactions are too weak to support any two-body states.
      These new states thus share this surprising scenario with the Efimov effect, but
      are not themselves Efimov states. Our effect occurs for both identical bosons and
      identical fermions, and it persists in the presence of two-body bound states.

PMID- 23003248
TI  - Validity of factorization of the high-energy photoelectron yield in above
      threshold ionization of an atom by a short laser pulse.
AB  - An analytic description for the yield, P(p), of high-energy electrons ionized
      from an atom by a short (few-cycle) laser pulse is obtained quantum mechanically.
      Factorization of P(p) in terms of an electron wave packet and the cross section
      for elastic electron scattering (EES) is shown to occur only for an ultrashort
      pulse, while in general P(p) involves interference of EES amplitudes with laser
      field-dependent momenta. The analytic predictions agree well with accurate
      numerical results.

PMID- 23003252
TI  - Ultrafast tunable optical delay line based on indirect photonic transitions.
AB  - We introduce the concept of an indirect photonic transition and demonstrate its
      use in a dynamic delay line to alter the group velocity of an optical pulse.
      Operating on an ultrafast time scale, we show continuously tunable delays of up
      to 20 ps, using a slow light photonic crystal waveguide only 300 MUm in length.
      Our approach is flexible, in that individual pulses in a pulse stream can be
      controlled independently, which we demonstrate by operating on pulses separated
      by just 30 ps. The two-step indirect transition is demonstrated here with a 30%
      conversion efficiency.

PMID- 23003253
TI  - Direct generation of polarization-entangled photon pairs in a poled fiber.
AB  - We experimentally demonstrate the direct generation of polarization-entangled
      photon pairs in an optical fiber at room temperature by exploiting type-II phase
      matched spontaneous parametric down-conversion. A second-order nonlinearity is
      artificially induced in the 17-cm-long weakly birefringent step-index fiber
      through the process of thermal poling, and quasi-phase-matching allows for the
      generation of entangled photons in the 1.5-micron telecom band when the fiber is
      pumped at 775 nm. A greater-than 80:1 coincidence-to-accidental ratio is
      achieved, limited mainly by multiphoton pair generation. Without the need to
      subtract accidentals or to compensate for walk-off, the raw two-photon
      interference visibility is found to be better than 95%, and violation of Bell's
      inequality is observed by more than 18 standard deviations. This makes for a
      truly alignment-free, plug-and-play source of polarization-entangled photon
      pairs.

PMID- 23003254
TI  - Spatial Power Combination for Omnidirectional Radiation via Anisotropic
      Metamaterials.
AB  - We present an efficient approach to realize the spatial power combination for
      omnidirectional radiation via metamaterials in the two-dimensional case. We
      propose a radially anisotropic zero-index metamaterial which can always produce
      ominidirectional radiation, independent of the number and position of the sources
      inside the metamaterial. When the radial component of the permeability tensor is
      approaching zero and the wave impedance is equal to that of free space, waves
      emitted from all sources inside the metamaterial are transformed into perfectly
      cylindrical waves without any reflection, and powers from different sources can
      be combined together to enhance the omnidirectional radiation. We have designed
      and fabricated such a radially anisotropic metamaterial, and both numerical and
      experimental results demonstrate the spatial power combination with high
      efficiency. The proposed idea can be extended to the three-dimensional case to
      generate perfectly coherent isotropic radiation in nature, which does not exist
      now. Metamaterial is a unique approach to obtain such a high-efficiency spatial
      power combination for omnidirectional radiation and isotropic radiation.

PMID- 23003255
TI  - Adler synchronization of spatial laser solitons pinned by defects.
AB  - Defects due to growth fluctuations in broad-area semiconductor lasers induce
      pinning and frequency shifts of spatial laser solitons. The effects of defects on
      the interaction of two solitons are considered in lasers with frequency-selective
      feedback both theoretically and experimentally. We demonstrate frequency and
      phase synchronization of paired laser solitons as their detuning is varied. In
      both theory and experiment the locking behavior is well described by the Adler
      model for the synchronization of coupled oscillators.

PMID- 23003256
TI  - Diodelike asymmetric transmission of linearly polarized waves using
      magnetoelectric coupling and electromagnetic wave tunneling.
AB  - An asymmetric, reciprocal, diffraction-free transmission of linearly polarized
      waves in a new diodelike, three-layer, ultrathin, chiral structure is studied
      theoretically and experimentally. The exploited physical mechanism is based on
      the maximization of the cross-polarized transmission in one direction due to the
      polarization selectivity dictated by the peculiar eigenstate combination, which
      is efficiently controlled by the electromagnetic tunneling through the metallic
      subwavelength mesh sandwiched between these layers. Simulation and microwave
      experiment results demonstrate a nearly total intensity transmission at normal
      incidence in one direction and a small intensity transmission in the opposite
      direction.

PMID- 23003257
TI  - Nonlinear modes in finite-dimensional PT-symmetric systems.
AB  - By rearrangements of waveguide arrays with gain and losses one can simulate
      transformations among parity-time (PT-) symmetric systems not affecting their
      pure real linear spectra. Subject to such transformations, however, the nonlinear
      properties of the systems undergo significant changes. On an example of an array
      of four waveguides described by the discrete nonlinear Schrodinger equation with
      dissipation and gain, we show that the equivalence of the underlying linear
      spectra does not imply similarity of the structure or stability of the nonlinear
      modes in the arrays. Even the existence of one-parametric families of nonlinear
      modes is not guaranteed by the PT symmetry of a newly obtained system. In
      addition, the stability is not directly related to the PT symmetry: stable
      nonlinear modes exist even when the spectrum of the linear array is not purely
      real. We use a graph representation of PT-symmetric networks allowing for a
      simple illustration of linearly equivalent networks and indicating their possible
      experimental design.

PMID- 23003258
TI  - Role of magnetic induction currents in nanoslit excitation of surface plasmon
      polaritons.
AB  - We present a method for exciting surface plasmon polaritons (SPPs) caused by a
      magnetic field component perpendicular to the direction of slit. The excitation
      mechanism is based on the spatially oscillating induced current along the edges
      of the slit under obliquely incident electromagnetic waves. Our finding
      distinguishes itself from previous mechanisms based on transverse electric fields
      and unveils the missing point of the SPP-excitation problem in a nanoslit. The
      use of a magnetic field for SPP excitation can be highly efficient and even
      comparable to that with an electric field, so that their composition can lead to
      selective unidirectional excitation.

PMID- 23003259
TI  - Controlling synchronization in large laser networks.
AB  - Synchronization in large laser networks with both homogeneous and heterogeneous
      coupling delay times is examined. The number of synchronized clusters of lasers
      is established to equal the greatest common divisor of network loops. We
      experimentally demonstrate up to 16 multicluster phase synchronization scenarios
      within unidirectional coupled laser networks, whereby synchronization in
      heterogeneous networks is deduced by mapping to an equivalent homogeneous
      network. The synchronization in large laser networks is controlled by means of
      tunable coupling and self-coupling.

PMID- 23003260
TI  - Topological changes in periodicity hubs of dissipative systems.
AB  - We reveal the existence of a new codimension-1 curve that involves a topological
      change in the structure of the chaotic invariant sets (attractors and saddles) in
      generic three-dimensional dissipative systems with Shilnikov saddle foci. This
      curve is related to the spiral-like structures of periodicity hubs that appear in
      the biparameter phase plane. We show how this curve configures the spiral
      structure (via the doubly superstable points) originated by the existence of
      Shilnikov homoclinics and how it separates two regions with different kinds of
      chaotic attractors or chaotic saddles. Inside each region, the topological
      structure is the same for both chaotic attractors and saddles.

PMID- 23003261
TI  - Stress wave anisotropy in centered square highly nonlinear granular systems.
AB  - Highly ordered, close packed granular systems present a nonlinear dynamic
      behavior stemming from the Hertzian contact interaction between particles. We
      investigated the propagation of elastic stress waves in an uncompressed, centered
      square array of spherical and cylindrical particles. We show, via experiments and
      numerical simulations, that systematic variations of the mass and stiffness
      ratios of the spherical and cylindrical particles lead to large variations in the
      characteristics of the propagating stress wave fronts traveling through the
      system. The ability to control the stress wave front properties in these granular
      systems may allow for the development of new wave-tailoring materials including
      systems capable of redirecting impact energy.

PMID- 23003262
TI  - Enhancement of mechanical Q factors by optical trapping.
AB  - The quality factor of a mechanical resonator is an important figure of merit for
      various sensing applications and for observing quantum behavior. Here, we
      demonstrate a technique to push the quality factor of a micromechanical resonator
      beyond conventional material and fabrication limits by using an optical field to
      stiffen or trap a particular motional mode. Optical forces increase the
      oscillation frequency by storing most of the mechanical energy in a nearly
      lossless optical potential, thereby strongly diluting the effect of material
      dissipation. By placing a 130 nm thick SiO2 pendulum in an optical standing wave,
      we achieve an increase in the pendulum center-of-mass frequency from 6.2 to 145
      kHz. The corresponding quality factor increases 50-fold from its intrinsic value
      to a final value of Q=5.8(1.1)*10(5), representing more than an order of
      magnitude improvement over the conventional limits of SiO2 for this geometry. Our
      technique may enable new opportunities for mechanical sensing and facilitate
      observations of quantum behavior in this class of mechanical systems.

PMID- 23003263
TI  - Heat flux manipulation with engineered thermal materials.
AB  - Utilizing a multilayered composite approach, we have designed and constructed a
      new class of artificial materials for thermal conduction. We show that an
      engineered material can be utilized to control the diffusive heat flow in ways
      inconceivable with naturally occurring materials. By shielding, concentrating,
      and inverting heat current, we experimentally demonstrate the unique potential
      and the utility of guiding heat flux.

PMID- 23003264
TI  - Prescribed pattern transformation in swelling gel tubes by elastic instability.
AB  - We present a study on swelling-induced circumferential buckling of tubular shaped
      gels. Inhomogeneous stress develops as the gel swells under mechanical
      constraints, which gives rise to spontaneous buckling instability without an
      external force. Full control over the postbuckling pattern is experimentally
      demonstrated. A simple analytical model is developed using elastic energy to
      predict stability and postbuckling patterns upon swelling. Analysis reveals that
      the height to diameter ratio is the most critical design parameter to determine
      the buckling pattern, which agrees well with experimental and numerical results.

PMID- 23003265
TI  - Stochastic and deterministic vector chromatography of suspended particles in one
      dimensional periodic potentials.
AB  - We present a comprehensive description of vector chromatography (VC) that
      includes deterministic and stochastic transport in one-dimensional periodic free
      energy landscapes, with both energetic and entropic contributions, and identifies
      the parameters governing the deflection angle. We also investigate the dependence
      of the deflection angle on the shape of the free-energy landscape by varying the
      width of the linear transitions in an otherwise dichotomous potential. Finally,
      we present experimental results obtained in a microfluidic system in which
      gravity drives the suspended particles and, in combination with a bottom surface
      patterned with shallow rectangular grooves, creates a periodic landscape of
      (potential) energy barriers. The experiments validate the model and demonstrate
      that a simple, passive microdevice can lead to VC of colloidal particles based on
      both size and density. More generally, other fields, e.g., electric,
      dielectrophoretic, or magnetic, can play or enhance the role of gravity,
      potentially leading to a versatile technique.

PMID- 23003266
TI  - Edge state in pipe flow experiments.
AB  - Recent numerical studies suggest that in pipe and related shear flows, the region
      of phase space separating laminar from turbulent motion is organized by a chaotic
      attractor, called an edge state, which mediates the transition process. We here
      confirm the existence of the edge state in laboratory experiments. We observe
      that it governs the dynamics during the decay of turbulence underlining its
      potential relevance for turbulence control. In addition we unveil two unstable
      traveling wave solutions underlying the experimental flow fields. This
      observation corroborates earlier suggestions that unstable solutions organize
      turbulence and its stability border.

PMID- 23003267
TI  - Universal dissipation scaling for nonequilibrium turbulence.
AB  - It is experimentally shown that the nonclassical high Reynolds number energy
      dissipation behavior, C(epsilon)=epsilonL/u(3)=f(Re(M))/Re(L), observed during
      the decay of fractal square grid-generated turbulence (where Re(M) is a global
      inlet Reynolds number and Re(L) is a local turbulence Reynolds number) is also
      manifested in decaying turbulence originating from various regular grids. For
      sufficiently high values of the global Reynolds numbers Re(M), f(Re(M))~Re(M).

PMID- 23003268
TI  - Separation of chiral particles in micro- or nanofluidic channels.
AB  - We propose a method to separate enantiomers in microfluidic or nanofluidic
      channels. It requires flow profiles that break chiral symmetry and have regions
      with high local shear. Such profiles can be generated in channels confined by
      walls with different hydrodynamic boundary conditions (e.g., slip lengths).
      Because of a nonlinear hydrodynamic effect, particles with different chirality
      migrate at different speeds and can be separated. The mechanism is demonstrated
      by computer simulations. We investigate the influence of thermal fluctuations
      (i.e., the Peclet number) and show that the effect disappears in the linear
      response regime. The details of the microscopic flow are important and determine
      which volume forces are necessary to achieve separation.

PMID- 23003269
TI  - Scaling and statistics in three-dimensional compressible turbulence.
AB  - The scaling and statistical properties of three-dimensional compressible
      turbulence are studied using high-resolution numerical simulations and a
      heuristic model. The two-point statistics of the solenoidal component of the
      velocity field are found to be not significantly different from those of
      incompressible turbulence, while the scaling exponents of the velocity structure
      function for the compressive component become saturated at high orders. Both the
      simulated flow and the heuristic model reveal the presence of a power-law tail in
      the probability density function of negative velocity divergence (high
      compression regime). The power-law exponent is different from that in Burgers
      turbulence, and this difference is shown to have a major contribution from the
      pressure effect, which is absent in the Burgers turbulence.

PMID- 23003270
TI  - Plasmoid ejection and secondary current sheet generation from magnetic
      reconnection in laser-plasma interaction.
AB  - Reconnection of the self-generated magnetic fields in laser-plasma interaction
      was first investigated experimentally by Nilson et al. [Phys. Rev. Lett. 97,
      255001 (2006)] by shining two laser pulses a distance apart on a solid target
      layer. An elongated current sheet (CS) was observed in the plasma between the two
      laser spots. In order to more closely model magnetotail reconnection, here two
      side-by-side thin target layers, instead of a single one, are used. It is found
      that at one end of the elongated CS a fanlike electron outflow region including
      three well-collimated electron jets appears. The (>1 MeV) tail of the jet energy
      distribution exhibits a power-law scaling. The enhanced electron acceleration is
      attributed to the intense inductive electric field in the narrow electron
      dominated reconnection region, as well as additional acceleration as they are
      trapped inside the rapidly moving plasmoid formed in and ejected from the CS. The
      ejection also induces a secondary CS.

PMID- 23003271
TI  - Effect of drift waves on plasma blob dynamics.
AB  - Most of the work to date on plasma blobs found in the edge region of magnetic
      confinement devices is limited to 2D theory and simulations which ignore the
      variation of blob parameters along the magnetic field line. However, if the 2D
      convective rate of blobs is on the order of the growth rate of unstable drift
      waves, then drift wave turbulence can drastically alter the dynamics of blobs
      from that predicted by 2D theory. The density gradients in the drift plane that
      characterize the blob are mostly depleted during the nonlinear stage of drift
      waves resulting in a much more diffuse blob with a greatly reduced radial
      velocity. Sheath connected plasma blobs driven by effective gravity forces are
      considered in this Letter and it is found that the effects of resistive drift
      waves occur at earlier stages in the 2D motion for smaller blobs and in systems
      with a smaller effective gravity force. These conclusions are supported
      numerically by a direct comparison of 2D and 3D seeded blob simulations.

PMID- 23003272
TI  - Driving sudden current and voltage in expanding and compressing plasma.
AB  - A magnetized plasma preseeded with an initially undamped Langmuir wave is shown
      to transition suddenly to a collisionless damping regime upon expansion of the
      plasma perpendicular to the background magnetic field. The resulting anisotropic
      fast-particle distribution then leads to an electrical current and dc voltage
      induction. The current drive efficiency of this effect in nonstationary plasmas
      is shown to depend on the rate of expansion of the plasma, the time-varying
      collisionality, and the plasma L/R time. Subsequent recompression of the plasma
      enhances this current drive effect by reducing further the collision rate of the
      current-carrying electrons.

PMID- 23003275
TI  - Quantum degenerate dipolar Fermi gas.
AB  - We report the first quantum degenerate dipolar Fermi gas, the realization of
      which opens a new frontier for exploring strongly correlated physics and, in
      particular, quantum liquid crystalline phases. A quantum degenerate Fermi gas of
      the most magnetic atom 161Dy is produced by laser cooling to 10 MUK before
      sympathetically cooling with ultracold, bosonic 162Dy. The temperature of the
      spin-polarized 161Dy is a factor T/T(F)=0.2 below the Fermi temperature T(F)=300
      nK. The cotrapped 162Dy concomitantly cools to approximately T(c) for Bose
      Einstein condensation, thus realizing a novel, nearly quantum degenerate dipolar
      Bose-Fermi gas mixture. Additionally, we achieve the forced evaporative cooling
      of spin-polarized 161Dy without 162Dy to T/T(F)=0.7. That such a low temperature
      ratio is achieved may be a first signature of universal dipolar scattering.

PMID- 23003273
TI  - Precision shock tuning on the national ignition facility.
AB  - Ignition implosions on the National Ignition Facility [J. D. Lindl et al., Phys.
      Plasmas 11, 339 (2004)] are underway with the goal of compressing deuterium
      tritium fuel to a sufficiently high areal density (rhoR) to sustain a self
      propagating burn wave required for fusion power gain greater than unity. These
      implosions are driven with a very carefully tailored sequence of four shock waves
      that must be timed to very high precision to keep the fuel entropy and adiabat
      low and rhoR high. The first series of precision tuning experiments on the
      National Ignition Facility, which use optical diagnostics to directly measure the
      strength and timing of all four shocks inside a hohlraum-driven, cryogenic liquid
      deuterium-filled capsule interior have now been performed. The results of these
      experiments are presented demonstrating a significant decrease in adiabat over
      previously untuned implosions. The impact of the improved shock timing is
      confirmed in related deuterium-tritium layered capsule implosions, which show the
      highest fuel compression (rhoR~1.0 g/cm(2)) measured to date, exceeding the
      previous record [V. Goncharov et al., Phys. Rev. Lett. 104, 165001 (2010)] by
      more than a factor of 3. The experiments also clearly reveal an issue with the
      4th shock velocity, which is observed to be 20% slower than predictions from
      numerical simulation.

PMID- 23003276
TI  - Preparation and spectroscopy of a metastable Mott-insulator state with attractive
      interactions.
AB  - We prepare and study a metastable attractive Mott-insulator state formed with
      bosonic atoms in a three-dimensional optical lattice. Starting from a Mott
      insulator with Cs atoms at weak repulsive interactions, we use a magnetic
      Feshbach resonance to tune the interactions to large attractive values and
      produce a metastable state pinned by attractive interactions with a lifetime on
      the order of 10 s. We probe the (de)excitation spectrum via lattice modulation
      spectroscopy, measuring the interaction dependence of two- and three-body bound
      state energies. As a result of increased on-site three-body loss we observe
      resonance broadening and suppression of tunneling processes that produce three
      body occupation.

PMID- 23003277
TI  - p-Type conductivity in N-doped ZnO: the role of the N(Zn)-V(O) complex.
AB  - Although nitrogen-doped zinc oxide has been fabricated as a light-emitting diode,
      the origin of its p-type conductivity remains mysterious. Here, by analyzing the
      surface reaction pathway of N in ZnO with first-principles density functional
      theory calculations, we demonstrate that the origin of p-type conductivity of N
      doped ZnO can originate from the defect complexes of N(Zn)-V(O) and N(O)-V(Zn).
      Favored by the Zn-polar growth, the shallow acceptor of N(O)-V(Zn) actually
      evolves from the double-donor state of N(Zn)-V(O). While N(Zn)-V(O) is
      metastable, the p-doping mechanism of N(Zn)-V(O)->N(O)-V(Zn) in ZnO will be free
      from the spontaneous compensation from the intrinsic donors. The results may
      offer clearer strategies for doping ZnO p-type more efficiently with N.

PMID- 23003274
TI  - Assembly of high-areal-density deuterium-tritium fuel from indirectly driven
      cryogenic implosions.
AB  - The National Ignition Facility has been used to compress deuterium-tritium to an
      average areal density of ~1.0+/-0.1 g cm(-2), which is 67% of the ignition
      requirement. These conditions were obtained using 192 laser beams with total
      energy of 1-1.6 MJ and peak power up to 420 TW to create a hohlraum drive with a
      shaped power profile, peaking at a soft x-ray radiation temperature of 275-300
      eV. This pulse delivered a series of shocks that compressed a capsule containing
      cryogenic deuterium-tritium to a radius of 25-35 MUm. Neutron images of the
      implosion were used to estimate a fuel density of 500-800 g cm(-3).

PMID- 23003278
TI  - BaTiO3(001)-(2*1): surface structure and spin density.
AB  - Using surface x-ray diffraction and ab initio calculations we present a model of
      the BaTiO3(001)-(2*1) surface structure, which has not been considered so far.
      While the crystal is terminated by two TiO2 layers similarly to SrTiO3(001)
      (2*1), we find that one out of two surface layer Ti-atoms resides in a tetragonal
      pyramidal oxygen environment. This peculiar geometry leads to a metallic and
      magnetic surface involving local magnetic moments up to 2MU(B) in magnitude
      located at surface Ti and O atoms. Our results are important for the
      understanding of the intrinsic surface metallicity of insulating oxides in
      general.

PMID- 23003279
TI  - Prediction and hydrogen acceleration of ordering in iron-vanadium alloys.
AB  - Ab initio calculations of binary metallic systems often predict ordered compounds
      in contrast to empirical reports of solid solutions or disordered phases. These
      discrepancies are usually attributed to slow kinetics that retains metastable
      structures at low temperatures. The Fe-V system is an example of this phenomenon,
      in which we predict two ordered stable ground states, Fe3V and FeV3, whereas a
      disordered sigma phase is reported. We propose to overcome this difficulty by
      hydrogen absorption, which facilitates metal atom mobility through vacancy
      formation and separation between the two elements due to their opposite
      affinities towards it, thus accelerating transformation kinetics. Hydrogen also
      increases the relative stability of the ordered structures compared with that of
      the sigma phase without affecting the shape of the phase diagram. The hydrogen
      induced formation of the ordered structures is expressed by a reversible decrease
      of the electrical resistivity with increasing hydrogen pressure. Such behavior
      has not been reported before in thin H absorbing films. Formation of the ordered
      structures is further substantiated by the kinetics of the resistivity changes
      upon variation of the hydrogen pressure, where two stages are distinguished: a
      fast initial stage and a much slower subsequent process in which the resistivity
      changes direction, associated with hydrogen dissolution and phase transformation,
      respectively.

PMID- 23003280
TI  - Boiling crisis as a critical phenomenon.
AB  - We present the first experimental study of intermittency and avalanche
      distribution during a boiling crisis. To understand the emergence of power law
      statistics we propose a simple spin model capturing the measured critical
      exponent. The model suggests that behind the critical heat flux is a percolation
      phenomenon involving drying-rewetting competition close to the hot surface.

PMID- 23003281
TI  - Microscopic origin of the reduced thermal conductivity of silicon nanowires.
AB  - We designed nanowires with a tailored surface structure and composition and with
      specific core defects to investigate the microscopic origin of the reduced
      thermal conductivity of Si at the nanoscale. We considered a diameter (15 nm)
      comparable to that of systems fabricated in recent experiments and we computed
      the thermal conductivity using equilibrium molecular dynamics simulations. We
      found that the presence of a native oxide surface layer may account for a tenfold
      to ~30-fold decrease in conductivity, with respect to bulk Si, depending on the
      level of roughness. However it is only the combination of core defects and
      surface ripples that enables a decrease close to 2 orders of magnitude, similar
      to that reported experimentally.

PMID- 23003282
TI  - Uncovering molecular mechanisms of electrowetting and saturation with
      simulations.
AB  - Molecular dynamics simulations are used to explore the physical mechanisms of
      electrowetting and the limits of continuum theories. Nanoscale drops exhibit the
      same behavior seen in macroscopic experiments: The contact angle theta follows
      continuum theory at low voltages and then saturates. Saturation limits
      applications of electrowetting and its origin is of great interest. In the
      simulations, saturation occurs when ions are pulled from the drop by large local
      fields. Saturation can be controlled by changing temperature, screening, or the
      energy binding ions to the fluid. We show a local force balance equation for
      theta remains valid even after saturation and that the interface approaches the
      equilibrium contact angle within a few nanometers of the solid.

PMID- 23003283
TI  - Formation of a novel ordered Ni3Al surface structure by codeposition on
      NiAl(110).
AB  - The formation of a new type of ordered 2D Ni3Al overlayer by low-temperature
      codeposition on NiAl(110) is demonstrated by kinetic Monte Carlo simulation of a
      multisite atomistic lattice-gas model with a precise treatment of surface
      diffusion kinetics. Simultaneous codeposition with 3:1 Ni:Al yields poor ordering
      at 300 K but well-ordered structures by ~500 K. Sequential codeposition of Ni
      then Al yields unmixed core-ring nanostructures at 300 K but strong intermixing
      and ordering by ~500 K.

PMID- 23003284
TI  - Ordered array of single adatoms with remarkable thermal stability: Au/Fe3O4(001).
AB  - Gold deposited on the Fe3O4(001) surface at room temperature was studied using
      scanning tunneling microscopy (STM) and x-ray photoelectron spectroscopy (XPS).
      This surface forms a (?2 * ?2)R45 degrees  reconstruction, where pairs of Fe and
      neighboring O ions are slightly displaced laterally producing undulating rows
      with "narrow" and "wide" hollow sites. At low coverages, single Au adatoms adsorb
      exclusively at the narrow sites, with no significant sintering up to annealing
      temperatures of 400  degrees C. We propose the strong site preference to be
      related to charge and orbital ordering within the first subsurface layer of
      Fe3O4(001)-(?2 * ?2)R45 degrees . Because of its high thermal stability, this
      could prove an ideal model system for probing the chemical reactivity of single
      atomic species.

PMID- 23003285
TI  - Strong coupling superconductivity, pseudogap, and Mott transition.
AB  - An intricate interplay between superconductivity, pseudogap, and Mott transition,
      either bandwidth driven or doping driven, occurs in materials. Layered organic
      conductors and cuprates offer two prime examples. We provide a unified
      perspective of this interplay in the two-dimensional Hubbard model within
      cellular dynamical mean-field theory on a 2*2 plaquette and using the continuous
      time quantum Monte Carlo method as impurity solver. Both at half filling and at
      finite doping, the metallic normal state close to the Mott insulator is unstable
      to d-wave superconductivity. Superconductivity can destroy the first-order
      transition that separates the pseudogap phase from the overdoped metal, yet that
      normal state transition leaves its marks on the dynamic properties of the
      superconducting phase. For example, as a function of doping one finds a rapid
      change in the particle-hole asymmetry of the superconducting density of states.
      In the doped Mott insulator, the dynamical mean-field superconducting transition
      temperature T(c)(d) does not scale with the order parameter when there is a
      normal-state pseudogap. T(c)(d) corresponds to the local pair formation
      temperature observed in tunneling experiments and is distinct from the pseudogap
      temperature.

PMID- 23003286
TI  - Vibron quasibound state in the noncentrosymmetric tetragonal heavy-fermion
      compound CeCuAl3.
AB  - We have investigated the noncentrosymmetric tetragonal heavy-fermion
      antiferromagnetic compound CeCuAl3 (T(N)=2.5 K) using inelastic neutron
      scattering (INS). Our INS results unequivocally reveal the presence of three
      magnetic excitations centered at 1.3, 9.8, and 20.5 meV. These spectral features
      cannot be explained within the framework of crystal-electric-field models and
      recourse to Kramers' theorem for a 4f(1) Ce(3+) ion. To overcome these
      interpretational difficulties, we have generalized the vibron model of Thalmeier
      and Fulde for cubic CeAl(2) to tetragonal point-group symmetry with the
      theoretically calculated vibron form-factor. This extension provides a
      satisfactory explanation for the position and intensity of the three observed
      magnetic excitations in CeCuAl3, as well as their dependence on momentum transfer
      and temperature. On the basis of our analysis, we attribute the observed series
      of magnetic excitations to the existence of a vibron quasibound state.

PMID- 23003287
TI  - Magnon-mediated interactions between fermions depend strongly on the lattice
      structure.
AB  - We propose two new methods to calculate exactly the spectrum of two spin-1/2
      charge carriers moving in a ferromagnetic background, at zero temperature. We
      find that if the spins are located on a different sublattice than that on which
      the fermions move, magnon-mediated effective interactions are very strong and can
      bind the fermions into low-energy bipolarons with triplet character. This never
      happens in models where spins and charge carriers share the same lattice, whether
      they are in the same band or in different bands. This proves that effective one
      lattice models do not describe correctly the low-energy part of the two-carrier
      spectrum of a two-sublattice model, even though they may describe the low-energy
      single-carrier spectrum appropriately.

PMID- 23003288
TI  - Electronic structure of spatially aligned graphene nanoribbons on Au(788).
AB  - We report on a bottom-up approach of the selective and precise growth of
      subnanometer wide straight and chevron-type armchair nanoribbons (GNRs) on a
      stepped Au(788) surface using different specific molecular precursors. This
      process creates spatially well-aligned GNRs, as characterized by STM. High
      resolution direct and inverse photoemission spectroscopy of occupied and
      unoccupied states allows the determination of the energetic position and momentum
      dispersion of electronic states revealing the existence of band gaps of several
      electron volts for straight 7-armchair, 13-armchair, and chevron-type GNRs in the
      electronic structure.

PMID- 23003289
TI  - Non-Abelian gauge potentials in graphene bilayers.
AB  - We study the effect of spatial modulations in the interlayer hopping of graphene
      bilayers, such as those that arise upon shearing or twisting. We show that their
      single-particle physics, characterized by charge accumulation and recurrent
      formation of zero-energy bands as the pattern period L increases, is governed by
      a non-Abelian gauge potential arising in the low-energy electronic theory due to
      the coupling between layers. We show that such gauge-type couplings give rise to
      a potential that, for certain discrete values of L, spatially confines states at
      zero energy in particular regions of the moire patterns. We also draw the
      connection between the recurrence of the flat zero-energy bands and the non
      Abelian character of the potential.

PMID- 23003290
TI  - Quantized Hall effect and Shubnikov-de Haas oscillations in highly doped Bi2Se3:
      evidence for layered transport of bulk carriers.
AB  - Bi2Se3 is an important semiconductor thermoelectric material and a prototype
      topological insulator. Here we report observation of Shubnikov-de Hass
      oscillations accompanied by quantized Hall resistances (R(xy)) in highly doped n
      type Bi2Se3 with bulk carrier concentrations of few 10(19) cm(-3). Measurements
      under tilted magnetic fields show that the magnetotransport is 2D-like, where
      only the c-axis component of the magnetic field controls the Landau level
      formation. The quantized step size in 1/R(xy) is found to scale with the sample
      thickness, and average ~e(2)/h per quintuple layer. We show that the observed
      magnetotransport features do not come from the sample surface, but arise from the
      bulk of the sample acting as many parallel 2D electron systems to give a
      multilayered quantum Hall effect. In addition to revealing a new electronic
      property of Bi2Se3, our finding also has important implications for electronic
      transport studies of topological insulator materials.

PMID- 23003291
TI  - Spin transition in the nu=8/3 fractional quantum Hall effect.
AB  - We present here the results from a density dependent study of the activation
      energy gaps of the fractional quantum Hall effect states at Landau level fillings
      nu=8/3 and 7/3 in a series of high quality quantum wells. In the density range
      from 0.5*10(11) to 3*10(11) cm(-2), the 7/3 energy gap increases monotonically
      with increasing density, supporting its ground state being spin polarized. For
      the 8/3 state, however, its energy gap first decreases with increasing density,
      almost vanishes at n~0.8*10(11) cm(-2), and then turns around and increases with
      increasing density, clearly demonstrating a spin transition.

PMID- 23003292
TI  - Dynamical aspects of strong pinning of magnetic vortices in type-II
      superconductors.
AB  - We determine the current-voltage characteristic of type-II superconductors in the
      presence of strong pinning centers. Focusing on a small density of defects, we
      derive a generic form for the characteristic with a linear flux-flow branch
      shifted by the critical current (excess-current characteristic). The details near
      onset, a hysteretic jump (for kappa>>1) or a smooth velocity turn-on (kappa->1),
      depend on the Labusch parameter kappa characterizing the pinning centers. Pushing
      the single-pin analysis into the weak pinning domain, we reproduce the collective
      pinning results for the critical current.

PMID- 23003293
TI  - Giant resistance change across the phase transition in spin-crossover molecules.
AB  - The electronic origin of a large resistance change in nanoscale junctions
      incorporating spin-crossover molecules is demonstrated theoretically by using a
      combination of density functional theory and the nonequilibrium Green's function
      method for quantum transport. At the spin-crossover phase transition, there is a
      drastic change in the electronic gap between the frontier molecular orbitals. As
      a consequence, when the molecule is incorporated in a two-terminal device, the
      current increases by up to 4 orders of magnitude in response to the spin change.
      This is equivalent to a magnetoresistance effect in excess of 3000%. Since the
      typical phase transition critical temperature for spin-crossover compounds can be
      extended to well above room temperature, spin-crossover molecules appear as the
      ideal candidate for implementing spin devices at the molecular level.

PMID- 23003294
TI  - Prediction of giant spin motive force due to Rashba spin-orbit coupling.
AB  - Magnetization dynamics in a ferromagnet can induce a spin-dependent electric
      field through a spin motive force. Spin current generated by the spin-dependent
      electric field can in turn modify the magnetization dynamics through spin
      transfer torque. While this feedback effect is usually weak and thus ignored, we
      predict that in Rashba spin-orbit coupling systems with a large Rashba parameter
      alpha(R), the coupling generates the spin-dependent electric field [+/
      (alpha(R)m(e)/eh)(z[over ^]*?m/?t)], which can be large enough to modify the
      magnetization dynamics significantly. This effect should be relevant for device
      applications based on ultrathin magnetic layers with strong Rashba spin-orbit
      coupling.

PMID- 23003295
TI  - Magnetic Coulomb fields of monopoles in spin ice and their signatures in the
      internal field distribution.
AB  - Fractionalization-the breaking up of an apparently indivisible microscopic degree
      of freedom-is one of the most counterintuitive phenomena in many-body physics.
      Here we study its most fundamental manifestation in spin ice, the only known
      fractionalized magnetic compound in 3D: we directly visualize the 1/r(2) magnetic
      Coulomb field of monopoles that emerge as the atomic magnetic dipoles
      fractionalize. We analyze the internal magnetic field distribution, relevant for
      local experimental probes. In particular, we present new zero-field NMR
      measurements that exhibit excellent agreement with the calculated line shapes,
      noting that this experimental technique can in principle measure directly the
      monopole density in spin ice. The distribution of field strengths is captured by
      a simple analytical form that exhibits a low density of low-field sites-in
      apparent disagreement with reported muon spin rotation results.
      Counterintuitively, the density of low-field locations decreases as the local
      ferromagnetic correlations imposed by the ice rules weaken.

PMID- 23003296
TI  - Spin-wave excitation in magnetic insulators by spin-transfer torque.
AB  - We study the excitation of spin waves in magnetic insulators by the current
      induced spin-transfer torque. We predict preferential excitation of surface spin
      waves induced by an easy-axis surface anisotropy with critical current inversely
      proportional to the penetration depth and surface anisotropy. The surface modes
      strongly reduce the critical current and enhance the excitation power of the
      current-induced magnetization dynamics.

PMID- 23003297
TI  - Charge order at the frontier between the molecular and solid states in
      Ba3NaRu2O9.
AB  - We show that the valence electrons of Ba3NaRu2O9, which has a quasimolecular
      structure, completely crystallize below 210 K. Using an extended Hubbard model,
      we show that the charge ordering instability results from long-range Coulomb
      interactions. However, orbital ordering, metal-metal bonding, and formation of a
      partial spin gap enforce the magnitude of the charge separation. The striped
      charge order and frustrated hcp lattice of Ru2O9 dimers lead to competition with
      a quasidegenerate charge-melted phase under photoexcitation at low temperature.
      Our results establish a broad class of simple metal oxides as models for emergent
      phenomena at the border between the molecular and solid states.

PMID- 23003298
TI  - Antiferromagnetic S=1/2 spin chain driven by p-orbital ordering in CsO2.
AB  - We demonstrate, using a combination of experiment and density functional theory,
      that orbital ordering drives the formation of a one-dimensional (1D) S=1/2
      antiferromagnetic spin chain in the 3D rocksalt structure of cesium superoxide
      (CsO2). The magnetic superoxide anion (O2(-)) exhibits degeneracy of its 2p
      derived molecular orbitals, which is lifted by a structural distortion on
      cooling. A spin chain is then formed by zigzag ordering of the half-filled
      superoxide orbitals, promoting a superexchange pathway mediated by the p(z)
      orbitals of Cs(+) along only one crystal direction. This scenario is analogous to
      the 3d-orbital-driven spin chain found in the perovskite KCuF3 and is the first
      example of an inorganic quantum spin system with unpaired p electrons.

PMID- 23003299
TI  - Coexisting order and disorder hidden in a quasi-two-dimensional frustrated
      magnet.
AB  - Frustrated magnetic interactions in a quasi-two-dimensional [111] slab of
      pyrochlore lattice were studied. For uniform nearest neighbor (NN) interactions,
      we show that the complex magnetic problem can be mapped onto a model with two
      independent degrees of freedom, tricolor and binary sign. This provides a
      systematic way to construct the complex classical spin ground states with
      collinear and coplanar bipyramid spins. We also identify "partial but extended"
      zero-energy excitations amongst the ground states. For nonuniform NN
      interactions, the coplanar ground state can be obtained from the collinear
      bipyramid spin state by collectively rotating two spins of each tetrahedron with
      an angle alpha in an opposite direction. The latter model with alpha~30 degrees 
      fits the experimental neutron data from SrCr(9p)Ga(12-9p)O(19) well.

PMID- 23003300
TI  - Phonon energy gaps in the charged incommensurate planes of the spin-ladder
      Sr14Cu24O41 compound by Raman and infrared spectroscopy.
AB  - The terahertz (THz) excitations in the quantum spin-ladder system Sr14Cu24O41
      have been determined along the c axis using THz time-domain, Raman, and infrared
      spectroscopy. Low-frequency infrared and Raman active modes are observed above
      and below the charge-ordering temperature T(co) is approximately equal to 200 K
      over a narrow interval approximately equal to 1-2 meV approximately equal to 8-16
      cm(-1)). A new infrared mode at approximately equal to 1 meV develops below
      approximately equal to 100 K. The temperature dependence of these modes shows
      that they are coupled to the charge- and spin-density-wave correlations in this
      system. These low-energy features are conjectured to originate in the gapped
      sliding motion of the chain and ladder subsystems, which are both incommensurate
      and charged.

PMID- 23003301
TI  - Ultrafast transitions from solid to liquid and plasma states of graphite induced
      by x-ray free-electron laser pulses.
AB  - We used photon pulses from an x-ray free-electron laser to study ultrafast x-ray
      induced transitions of graphite from solid to liquid and plasma states. This was
      accomplished by isochoric heating of graphite samples and simultaneous probing
      via Bragg and diffuse scattering at high time resolution. We observe that
      disintegration of the crystal lattice and ion heating of up to 5 eV occur within
      tens of femtoseconds. The threshold fluence for Bragg-peak degradation is smaller
      and the ion-heating rate is faster than current x-ray-matter interaction models
      predict.

PMID- 23003302
TI  - Enhancing the nonlinear optical response using multifrequency gold-nanowire
      antennas.
AB  - We introduce and experimentally demonstrate the concept of multifrequency optical
      antennas that are designed for controlling the nonlinear response of materials.
      These antennas consist of two arms of different lengths, each resonant with one
      of the incoming frequencies. They are embedded in a nonlinear medium (indium tin
      oxide) that acts as a receiver. Because the two arms have different spectral
      resonances, tuning of the antenna gap size has minimal effect on the linear
      optical properties. However, it strongly affects the nonlinear response. Thus, by
      employing antenna elements with different spectral resonances, we provide a
      strategy to decouple the nonlinear response of nanomaterials from their linear
      optical properties.

PMID- 23003303
TI  - Full-field near-field optical microscope for cell imaging.
AB  - We report a new full-field fluorescence microscopy method for imaging live cell
      membranes based on supercritical near-field emission. This technique consists of
      extracting the self-interference between undercritical and supercritical light by
      simple image subtraction. In the objective back focal plane, this is equivalent
      to adding a virtual mask blocking the subcritical emission. We show that this
      virtual mask is radically different from a real physical mask, enabling a 100 nm
      axial confinement and enhancing the image sensitivity without damaging the
      lateral resolution. This technique is easy to implement and simultaneously
      provides images of the inner parts of the cell and its membrane with standard
      illumination light.

PMID- 23003304
TI  - Spin-selective transport of electrons in DNA double helix.
AB  - The experiment that the high spin selectivity and the length-dependent spin
      polarization are observed in double-stranded DNA [Science 331, 894 (2011)], is
      elucidated by considering the combination of the spin-orbit coupling, the
      environment-induced dephasing, and the helical symmetry. We show that the spin
      polarization in double-stranded DNA is significant even in the case of weak spin
      orbit coupling, while no spin polarization appears in single-stranded DNA.
      Furthermore, the underlying physical mechanism and the parameter dependence of
      the spin polarization are studied.

PMID- 23003305
TI  - Characterizing concentrated, multiply scattering, and actively driven fluorescent
      systems with confocal differential dynamic microscopy.
AB  - We introduce confocal differential dynamic microscopy (ConDDM), a new technique
      yielding information comparable to that given by light scattering but in dense,
      opaque, fluorescent samples of micron-sized objects that cannot be probed easily
      with other existing techniques. We measure the correct wave vector q-dependent
      structure and hydrodynamic factors of concentrated hard-sphere-like colloids. We
      characterize concentrated swimming bacteria, observing ballistic motion in the
      bulk and a new compressed-exponential scaling of dynamics, and determine the
      velocity distribution; by contrast, near the coverslip, dynamics scale
      differently, suggesting that bacterial motion near surfaces fundamentally differs
      from that of freely swimming organisms.

PMID- 23003306
TI  - Nonlinear dynamics of a microswimmer in Poiseuille flow.
AB  - We study the three-dimensional dynamics of a spherical microswimmer in
      cylindrical Poiseuille flow which can be mapped onto a Hamiltonian system.
      Swinging and tumbling trajectories are identified. In 2D they are equivalent to
      oscillating and circling solutions of a mathematical pendulum. Hydrodynamic
      interactions between the swimmer and confining channel walls lead to dissipative
      dynamics and result in stable trajectories, different for pullers and pushers. We
      demonstrate this behavior in the dipole approximation of the swimmer and with
      simulations using the method of multiparticle collision dynamics.

PMID- 23003307
TI  - Cellular dewetting: opening of macroapertures in endothelial cells.
AB  - Pathogenic bacteria can cross from blood vessels to host tissues by opening
      transendothelial cell macroapertures (TEMs). To induce TEM opening, bacteria
      intoxicate endothelial cells with proteins that disrupt the contractile
      cytoskeletal network. Cell membrane tension is no longer resisted by contractile
      fibers, leading to the opening of TEMs. Here we model the opening of TEMs as a
      new form of dewetting. While liquid dewetting is irreversible, we show that
      cellular dewetting is transient. Our model predicts the minimum radius for hole
      nucleation, the maximum TEM size, and the dynamics of TEM opening, in good
      agreement with experimental data. The physical model is then coupled with
      biological experimental data to reveal that the protein missing in metastasis
      (MIM) controls the line tension at the rim of the TEM and opposes its opening.

PMID- 23003308
TI  - What phasons look like: particle trajectories in a quasicrystalline potential.
AB  - Among the distinctive features of quasicrystals-structures with long-range order
      but without periodicity-are phasons. Phasons are hydrodynamic modes that, like
      phonons, do not cost free energy in the long-wavelength limit. For light-induced
      colloidal quasicrystals, we analyze the collective rearrangements of the colloids
      that occur when the phasonic displacement of the light field is changed. The
      colloidal model system is employed to study the link between the continuous
      description of phasonic modes in quasicrystals and collective phasonic flips of
      atoms. We introduce characteristic areas of reduced phononic and phasonic
      displacements and use them to predict individual colloidal trajectories. In
      principle, our method can be employed with all quasicrystalline systems in order
      to derive collective rearrangements of particles from the continuous description
      of phasons.

PMID- 23003310
TI  - Small-world network spectra in mean-field theory.
AB  - Collective dynamics on small-world networks emerge in a broad range of systems
      with their spectra characterizing fundamental asymptotic features. Here we derive
      analytic mean-field predictions for the spectra of small-world models that
      systematically interpolate between regular and random topologies by varying their
      randomness. These theoretical predictions agree well with the actual spectra
      (obtained by numerical diagonalization) for undirected and directed networks and
      from fully regular to strongly random topologies. These results may provide
      analytical insights to empirically found features of dynamics on small-world
      networks from various research fields, including biology, physics, engineering,
      and social science.

PMID- 23003309
TI  - Noise-induced Forster resonant energy transfer between orthogonal dipoles in
      photoexcited molecules.
AB  - We show that Forster resonance energy transfer (FRET) in an orthogonally arranged
      donor-acceptor pair can be induced by environmental noise, although direct
      transfer is prohibited. Environmental fluctuations break the strict orthogonal
      dipole arrangement and cause effective fluctuating excitonic interactions. Using
      a scaling argument, we show that interaction fluctuations are coupled to those of
      the energy levels and are strong enough to induce large FRET rates. This
      mechanism also explains the temperature dependence observed in a recent
      experiment on a perylene bisimide dyad and predicts a modified distance
      dependence as compared to standard Forster theory.

PMID- 23003311
TI  - No need for conspiracy: self-organized cartel formation in a modified trust game.
AB  - We investigate the dynamics of a trust game on a mixed population, where
      individuals with the role of buyers are forced to play against a predetermined
      number of sellers whom they choose dynamically. Agents with the role of sellers
      are also allowed to adapt the level of value for money of their products, based
      on payoff. The dynamics undergoes a transition at a specific value of the
      strategy update rate, above which an emergent cartel organization is observed,
      where sellers have similar values of below-optimal value for money. This cartel
      organization is not due to an explicit collusion among agents; instead, it arises
      spontaneously from the maximization of the individual payoffs. This dynamics is
      marked by large fluctuations and a high degree of unpredictability for most of
      the parameter space and serves as a plausible qualitative explanation for
      observed elevated levels and fluctuations of certain commodity prices.

PMID- 23003312
TI  - Controlling complex networks: how much energy is needed?
AB  - The outstanding problem of controlling complex networks is relevant to many areas
      of science and engineering, and has the potential to generate technological
      breakthroughs as well. We address the physically important issue of the energy
      required for achieving control by deriving and validating scaling laws for the
      lower and upper energy bounds. These bounds represent a reasonable estimate of
      the energy cost associated with control, and provide a step forward from the
      current research on controllability toward ultimate control of complex networked
      dynamical systems.

PMID- 23003313
TI  - Comment on "Mechanism of void nucleation and growth in bcc Fe: atomistic
      simulations at experimental time scales".

PMID- 23003315
TI  - Comment on "Spin-canting-induced improper ferroelectricity and spontaneous
      magnetization reversal in SmFeO3".

PMID- 23003317
TI  - Comment on "Uncovering the complex behavior of hydrogen in Cu2O".

PMID- 23003319
TI  - Use of high resolution mass spectrometry for analysis of polymeric excipients in
      drug delivery formulations.
AB  - Two polymeric excipients, typically used in enabling drug delivery approaches,
      are Gelucire 44/14 (a product of Gattefosse s.a, St Priest, France) and
      polysorbate 80; these are known to improve solubility of poorly water-soluble
      drugs and, hence, increase their effective bioavailability. In addition to the
      use of Gelucire 44/14 and polysorbate 80 as excipients in drugs, they are also
      widely used as cosmetic and food additives. In general, complex structures and
      compositions of drug excipients impact performance of the formulation in vivo and
      consequently affect drug absorption. Therefore, a comparison between excipients
      from different suppliers and batches to batch would provide an indication of the
      impact on drug product performance and also the study of the effectiveness of the
      system and any problems associated with the formulation. In this study, high
      resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS)
      is used to compare two different batches of Gelucire 44/14 and polysorbate 80.
      With the high resolving power of FTICR MS, it was possible to differentiate
      between batches of excipients from differences in the identified components. The
      improved resolution offered by FTICR MS allowed assignment of four polymeric
      series differences in the two batches of polysorbate 80 and the presence of one
      compound and three polymeric series differences in the two batches of Gelucire
      44/14. The increase in the number of components assigned in the excipients batch
      using FTICR-MS, compared to the numbers previously assigned by lower resolution
      TOF MS, underlines the importance of high resolution techniques in analysis of
      highly complex mixtures.

PMID- 23003320
TI  - A comparison of human immunodeficiency virus, hepatitis C virus, hepatitis B
      virus, and human T-lymphotropic virus marker rates for directed versus volunteer
      blood donations to the American Red Cross during 2005 to 2010.
AB  - BACKGROUND: At most US blood centers, patients may still opt to choose specific
      donors to give blood for their anticipated transfusion needs. However, there is
      little evidence of improved safety with directed donation when compared to
      volunteer donation. STUDY DESIGN AND METHODS: The percentage of directed
      donations made to the American Red Cross (ARC) from 1995 to 2010 was determined.
      Infectious disease marker rates for human immunodeficiency virus (HIV), hepatitis
      C virus (HCV), hepatitis B virus (HBV), and human T-lymphotropic virus (HTLV)
      were calculated for volunteer and directed donations made from 2005 to 2010. Odds
      ratios (ORs) were calculated to compare marker-positive rates of directed
      donations to volunteer donations. RESULTS: The percentage of donations from
      directed donors declined from 1.6% in 1995 to 0.12% in 2010. From 2005 to 2010,
      the ARC collected 38,894,782 volunteer and 69,869 directed donations. Rates of
      HIV, HCV, HBV, and HTLV for volunteer donations were 2.9, 32.2, 12.4, and 2.5 per
      100,000 donations, respectively; for directed, the rates were 7.2, 93.0, 40.1,
      and 18.6 per 100,000. After demographics and first-time or repeat status were
      adjusted for, corresponding ORs of viral marker positivity in directed versus
      volunteer donations were not significant for HIV, HBV, or HTLV and significant
      for HCV (OR, 0.7; 95% confidence interval, 0.50-0.90). CONCLUSIONS: Directed
      donations have declined by 92% at the ARC since 1995, but have higher viral
      marker rates than volunteer donations. The difference can be explained in part by
      the effects of first-time or repeat status of the donors. Patients considering
      directed donation should be appropriately counseled about the potential risks.

PMID- 23003321
TI  - Systematic review: symptom assessment using patient-reported outcomes in
      gastroesophageal reflux disease and dyspepsia.
AB  - OBJECTIVE: The importance of symptom assessment using patient-reported outcomes
      (PROs) is becoming increasingly recognized in the management of upper
      gastrointestinal (GI) disease. The authors aimed to review systematically the
      methodological aspects of PRO instrument development and use in the GERD or
      dyspepsia literature, and to assess these instruments' properties in light of the
      Food and Drug Administration's (FDA) guidance. MATERIAL AND METHODS: Systematic
      PubMed and Embase searches (using terms based on the FDA guidance) identified
      studies that reported methodological aspects in developing or using PRO
      instruments for GERD or dyspepsia symptom measurement. RESULTS: Ten studies were
      identified (six systematically and four from citation lists). Studies reported
      the development or use of a relevant PRO instrument, with a focus on
      methodological aspects that the FDA guidance describes as important for patient
      understanding. Studies demonstrated heterogeneity of recall periods, symptoms and
      response options. Two studies demonstrated that a lack of consistent vocabulary
      may contribute to discrepancy in symptom reporting between investigators and
      patients. Two studies indicated that symptoms must be described in a manner that
      is relevant to patients. One study described the development of a PRO instrument
      separately in two languages, acknowledging linguistic and cultural differences
      between populations. One study demonstrated changes in symptom severity based on
      the recall period. CONCLUSIONS: There is considerable heterogeneity in the
      methodology used to develop PRO instruments for upper GI disease. Adherence to
      best practices in PRO development and validation may improve the quality and
      utility of these measures, leading to improved communication in clinical
      practice.

PMID- 23003322
TI  - A simple technique to perform manual dermabrasion with sandpaper.

PMID- 23003324
TI  - Role of hydrogen-bonding in the formation of polar achiral and nonpolar chiral
      vanadium selenite frameworks.
AB  - A series of organically templated vanadium selenites have been prepared under
      mild hydrothermal conditions. Single crystals were grown from mixtures of
      VOSO(4), SeO(2), and either 1,4-dimethylpiperazine, 2,5-dimethylpiperazine, or 2
      methylpiperazine in H(2)O. Each compound contains one-dimensional
      [VO(SeO(3))(HSeO(3))](n)(n-) secondary building units, which connect to form
      three-dimensional frameworks in the presence of 2,5-dimethylpiperazine or 2
      methylpiperazine. Differences in composition and both intra-secondary building
      unit and organic-inorganic hydrogen-bonding between compounds dictate the
      dimensionality of the resulting inorganic structures. [1,4
      dimethylpiperazineH(2)][VO(SeO(3))(HSeO(3))](2) contains one-dimensional
      [VO(SeO(3))(HSeO(3))](n)(n-) chains, while [2,5
      dimethylpiperazineH(2)][VO(SeO(3))(HSeO(3))](2).2H(2)O contains a three
      dimensional [VO(SeO(3))(HSeO(3))](n)(n-) framework. The use of racemic 2
      methylpiperazine also results in a compound containing a three-dimensional
      [VO(SeO(3))(HSeO(3))](n)(n-) framework, crystallizing in the noncentrosymmetric
      polar, achiral space group Pca2(1) (no. 29), while analogous reactions containing
      either (R)-2-methylpiperazine or (S)-2-methylpiperazine result in
      noncentrosymmetric, nonpolar chiral frameworks that crystallize in P2(1)2(1)2
      (no. 18). The formation of these noncentrosymmetric framework materials is
      dictated by the structure, symmetry, and hydrogen-bonding properties of the [2
      methylpiperazineH(2)](2+) cations.

PMID- 23003323
TI  - Spectroscopic and functional characterization of iron-sulfur cluster-bound forms
      of Azotobacter vinelandii (Nif)IscA.
AB  - The mechanism of [4Fe-4S] cluster assembly on A-type Fe-S cluster assembly
      proteins, in general, and the specific role of (Nif)IscA in the maturation of
      nitrogen fixation proteins are currently unknown. To address these questions, in
      vitro spectroscopic studies (UV-visible absorption/CD, resonance Raman and
      Mossbauer) have been used to investigate the mechanism of [4Fe-4S] cluster
      assembly on Azotobacter vinelandii(Nif)IscA, and the ability of (Nif)IscA to
      accept clusters from NifU and to donate clusters to the apo form of the
      nitrogenase Fe-protein. The results show that (Nif)IscA can rapidly and
      reversibly cycle between forms containing one [2Fe-2S](2+) and one [4Fe-4S](2+)
      cluster per homodimer via DTT-induced two-electron reductive coupling of two [2Fe
      2S](2+) clusters and O(2)-induced [4Fe-4S](2+) oxidative cleavage. This unique
      type of cluster interconversion in response to cellular redox status and oxygen
      levels is likely to be important for the specific role of A-type proteins in the
      maturation of [4Fe-4S] cluster-containing proteins under aerobic growth or
      oxidative stress conditions. Only the [4Fe-4S](2+)-(Nif)IscA was competent for
      rapid activation of apo-nitrogenase Fe protein under anaerobic conditions. Apo
      (Nif)IscA was shown to accept clusters from [4Fe-4S] cluster-bound NifU via rapid
      intact cluster transfer, indicating a potential role as a cluster carrier for
      delivery of clusters assembled on NifU. Overall the results support the proposal
      that A-type proteins can function as carrier proteins for clusters assembled on U
      type proteins and suggest that they are likely to supply [2Fe-2S] clusters rather
      than [4Fe-4S] for the maturation of [4Fe-4S] cluster-containing proteins under
      aerobic or oxidative stress growth conditions.

PMID- 23003325
TI  - Posterior predictive checks can and should be Bayesian: comment on Gelman and
      Shalizi, 'Philosophy and the practice of Bayesian statistics'.
AB  - Bayesian inference is conditional on the space of models assumed by the analyst.
      The posterior distribution indicates only which of the available parameter values
      are less bad than the others, without indicating whether the best available
      parameter values really fit the data well. A posterior predictive check is
      important to assess whether the posterior predictions of the least bad parameters
      are discrepant from the actual data in systematic ways. Gelman and Shalizi
      (2012a) assert that the posterior predictive check, whether done qualitatively or
      quantitatively, is non-Bayesian. I suggest that the qualitative posterior
      predictive check might be Bayesian, and the quantitative posterior predictive
      check should be Bayesian. In particular, I show that the 'Bayesian p-value', from
      which an analyst attempts to reject a model without recourse to an alternative
      model, is ambiguous and inconclusive. Instead, the posterior predictive check,
      whether qualitative or quantitative, should be consummated with Bayesian
      estimation of an expanded model. The conclusion agrees with Gelman and Shalizi
      regarding the importance of the posterior predictive check for breaking out of an
      initially assumed space of models. Philosophically, the conclusion allows the
      liberation to be completely Bayesian instead of relying on a non-Bayesian deus ex
      machina. Practically, the conclusion cautions against use of the Bayesian p-value
      in favour of direct model expansion and Bayesian evaluation.

PMID- 23003326
TI  - Reversing the polarity of bipolar stimulation in deep brain stimulation for
      essential tremor: a theoretical explanation for a useful clinical intervention.
AB  - The quadripolar electrodes used for deep brain stimulation are designed to give
      flexibility in contact configuration, optimize therapeutic effect, and minimize
      side-effects. A patient with essential tremor did not tolerate a bipolar setting
      due to the emergence of a pulling sensation in her face. However, when the
      polarity of the contacts was reversed, a 70% higher voltage was tolerated. Using
      an electric field model, we predicted that this effect was due to the proximity
      of the topmost contact to the internal capsule. Post-operative imaging supported
      this prediction. These results demonstrate how a multi-disciplinary approach
      allows us to optimize parameter settings. 

PMID- 23003327
TI  - Efficient inhibition of intraperitoneal ovarian cancer growth in nude mice by
      liposomal delivery of short hairpin RNA against STAT3.
AB  - AIM: Signal transducer and activator of transcription 3 (STAT3) plays an
      important role in the tumor formation, prognosis and chemoresistance of ovarian
      cancer. Our goal was to investigate the effect of silencing STAT3 on ovarian
      cancer cell apoptosis, proliferation, angiogenesis and expression of key targets
      in vitro and in vivo. METHODS: The ovarian cancer cell lines A2780CP and A2780s
      were used. STAT3 was knocked down by the plasmid-based short hairpin RNA (shRNA)
      expression system. In vitro, a colony formation assay and Hoechst staining were
      used to examine cell proliferation and apoptosis. The expression level of STAT3
      and apoptosis-related proteins were determined by Western blot. The A2780CP
      intraperitoneal model was used to evaluate the effect of shSTAT3 on tumor growth
      in mice. Proliferation, apoptosis, and angiogenesis in tumor tissues were
      measured by proliferating cell nuclear antigen, TUNEL and CD31 immunostaining,
      respectively. RESULTS: Treatment with shSTAT3 resulted in apoptosis and
      inhibition of cell proliferation in vitro. Western blot analysis demonstrated
      that shSTAT3 induced the expression of cleaved caspase-3 and reduced the
      expression of survivin, Bcl-2 and vascular endothelial growth factor. In vivo,
      the tumor weight was reduced to 13.46% of 5% glucose by shSTAT3/lipoplexes (P <
      0.01), accompanied with apoptosis induction (P < 0.01), proliferation inhibition
      (P < 0.01) and angiogenesis inhibition (P < 0.01). CONCLUSIONS: We find that
      treatment with shSTAT3 inhibits tumor growth in vitro and in vivo by inducing
      apoptosis and inhibiting cell proliferation. This work should provide the
      scientific foundation for future investigation of shSTAT3 as a strategy for
      ovarian cancer gene therapy and the combination of gene therapy with
      chemotherapy.

PMID- 23003328
TI  - Excitonic coupling in linear and trefoil trimer perylenediimide molecules probed
      by single-molecule spectroscopy.
AB  - Perylenediimide (PDI) molecules are promising building blocks for photophysical
      studies of electronic interactions within multichromophore arrays. Such PDI
      arrays are important materials for  fabrication of molecular nanodevices such as
      organic light-emitting diodes, organic semiconductors, and biosensors because of
      their high photostability, chemical and physical inertness, electron affinity,
      and high tinctorial strength over the entire visible spectrum. In this work, PDIs
      have been organized into linear (L3) and trefoil (T3) trimer molecules and
      investigated by single-molecule fluorescence microscopy to probe the relationship
      between molecular structures and interchromophoric electronic interactions. We 
      found a broad distribution of coupling strengths in both L3 and T3 and hence
      strong/weak coupling between PDI units by monitoring spectral peak shifts in
      single-molecule fluorescence spectra upon sequential photobleaching of each
      constituent chromophore. In addition, we  used a wide-field defocused imaging
      technique to resolve heterogeneities in molecular structures of L3 and T3
      embedded in a PMMA polymer matrix. A systematic comparison between the two sets
      of experimental results allowed us to infer the correlation between
      intermolecular interactions and molecular structures. Our results show  control
      of the PDI intermolecular interactions using suitable multichromophoric
      structures.

PMID- 23003330
TI  - Editorial Comment from Dr Mohta to circumcision with a novel disposable device in
      Chinese children: a randomized controlled trial.

PMID- 23003329
TI  - Evaluation of a novel continuous glucose monitoring-based method for mealtime
      insulin dosing--the iBolus--in subjects with type 1 diabetes using continuous
      subcutaneous insulin infusion therapy: a randomized controlled trial.
AB  - OBJECTIVE: Prandial insulin dosing is an empirical practice associated frequently
      with poor reproducibility in postprandial glucose response. Based on continuous
      glucose monitoring (CGM), a method for prandial insulin administration (iBolus)
      is presented and evaluated for people with type 1 diabetes using CSII therapy.
      SUBJECTS AND METHODS: An individual patient's model for a 5-h postprandial period
      was obtained from 6-day ambulatory CGM and used for iBolus calculation in 12
      patients with type 1 diabetes. In a double-blind, crossover study each patient
      underwent four meal tests with 40 g or 100 g of carbohydrates (CHOs), both on two
      occasions. For each meal, the iBolus or the traditional bolus (tBolus) was given
      before mealtime (t(0)) in a randomized order. We measured the postprandial
      glycemic response as the area under the curve of plasma glucose (AUC-PG(0-5h))
      and variability as the individual coefficient of variation (CV) of AUC-PG(0-5h).
      The contribution of the insulin-to-CHO ratio, CHO, plasma glucose at t(0)
      (PG(t0)), and insulin dose to AUC-PG(0-5h) and its CV was also investigated.
      RESULTS: AUC-PG(0-5h) was similar with either bolus for 40-g (iBolus vs. tBolus,
      585.5+/-127.5 vs. 689.2+/-180.7 mg/dL.h) or 100-g (752.1+/-237.7 vs. 760.0+/
      263.2 mg/dL.h) CHO meals. A multiple regression analysis revealed a significant
      model only for the tBolus, with PG(t0) being the best predictor of AUC-PG(0-5h)
      explaining approximately 50% of the glycemic response. Observed variability was
      greater with the iBolus (CV, 16.7+/-15.3% vs. 10.1+/-12.5%) but independent of
      the factors studied. CONCLUSIONS: A CGM-based algorithm for calculation of
      prandial insulin is feasible, although it does not reduce unpredictability of
      individual glycemic responses. Causes of variability need to be identified and
      analyzed for further optimization of postprandial glycemic control.

PMID- 23003331
TI  - Evaluation of strain-specific primers for identification of Lactobacillus
      rhamnosus GG.
AB  - Lactobacillus rhamnosus strain GG (ATCC 53103) is one of the most widely studied
      and commercialized probiotic strains, and thus strain-specific identification for
      the strain is highly valuable. In this study, two published PCR-based
      identification methods for strain GG, a transposase gene-targeting system and a
      phage-related gene-targeting system, were evaluated. The former produced
      amplicons from eight of the 41 strains tested and the phage-related system from
      five of the tested strains, including the strain GG. Fingerprinting analysis
      indicated that the strains LMG 18025, LMG 18030, and LMG 18038, which had an
      amplicon by the former system but none by the latter, were genetically
      distinguishable from L. rhamnosus GG at strain level. Strains LMG 23320, LMG
      23325, LMG 23534, and LMG 25859 showed profiles very similar to that of the
      strain GG, suggesting that these strains might be identical to GG or derivative
      strains of it. The results here indicated that the phage-related gene-targeting
      system is a good tool for accurate identification of L. rhamnosus GG. This system
      would be able to detect both the original L. rhamnosus GG and its derivative
      strains.

PMID- 23003332
TI  - Combined polymorphisms in oxidative stress genes predict coronary artery disease
      and oxidative stress in coronary angiography patients.
AB  - Oxidative stress has been implicated in all stages of atherosclerosis, but how
      inherited variations in oxidative stress genes influence the severity of
      cardiovascular disease is not known. We tested associations between polymorphisms
      in candidate oxidative stress genes, plasma oxidative stress biomarkers, and
      cardiovascular mortality in an angiography cohort. Single nucleotide
      polymorphisms (SNPs) across 15 genes were selected by linkage disequilibrium
      tagging. Genotyping was performed using customized arrayed primer extension micro
      arrays, with automated genotype calling methods. Effects of SNPs and haplotypes
      on plasma oxidative stress and coronary artery disease (CAD) were estimated using
      a stochastic estimation maximization algorithm. Proportionate hazards analyses
      were used to determine effects of single and combined genetic markers on
      cardiovascular mortality risk, and on the following oxidative stress biomarkers:
      myeloperoxidase (MPO), nitrotyrosine, oxidized low-density lipoprotein, and
      antioxidant capacity. Oxidative stress gene SNPs associated with CAD were
      combined into an oxidative stress risk allele score, which predicted disease
      presence (1.5-fold risk increase per allele, P < 0.001). Combined risk alleles
      were also associated with elevated plasma MPO (P < 0.003), an oxidative stress
      biomarker that predicts cardiovascular mortality. Genetic markers that represent
      lifetime oxidative stress burden may implicate specific oxidative stress pathways
      in the pathogenesis of atherosclerosis, and offer therapeutic opportunities.

PMID- 23003333
TI  - Chelation-controlled addition of organozincs to alpha-chloro aldimines.
AB  - Nucleophilic additions to alpha-chiral alpha-halo carbonyl derivatives are well
      known to generate Cornforth-Evans products via a nonchelation pathway. What was
      unprecedented before this report is C-X bonds reversing the diastereoselectivity
      through coordination to metals during C-C bond-forming reactions (chelation
      control). Herein we describe chelation control involving C-X bonds in highly
      diastereoselective additions of organozinc reagents to a variety of alpha-chloro
      aldimines. The unique ability of alkylzinc halide Lewis acids to coordinate to
      the Cl, N, and O of alpha-chloro sulfonyl imine substrates is supported by
      computational studies.

PMID- 23003334
TI  - Season-dependent postembryonic maturation of the diurnal rhythm of melatonin
      biosynthesis in the chicken pineal gland.
AB  - Previously, we have demonstrated that the timing of the nocturnal peak of
      activity of the pineal arylalkylamine-N-acetyltransferase - a key enzyme in the
      melatonin biosynthesis pathway - in 3-wk-old chickens kept from the day of hatch
      under controlled laboratory conditions (L:D 12:12) varies depending on the season
      of hatch (summer vs. winter). The present study was undertaken to answer the
      following questions: (1) are season-related differences seen in the level of
      transcription of genes encoding enzymes of the melatonin biosynthesis pathway?
      (2) Does the pineal content of the main precursor (serotonin) and the final
      product (melatonin) exhibit age- and season-related changes? (3) At which step in
      postembryonic development are these season-related variations in pineal gland
      function most pronounced? Male Hy-line chickens hatched in the summer or winter,
      from eggs laid by hens held on L:D 16:8, were kept from the day of hatch under
      L:D 12:12 conditions. At the age of 2, 9, or 16 d, chickens were sacrificed every
      2 h over a 24-h period and their pineal glands, isolated under dim red light,
      were processed for the measurement of (i) the level of Aanat and Asmt
      (acetylserotonin O-methyltransferase) mRNAs encoding the two last enzymes
      involved in melatonin biosynthesis, (ii) the activity of these enzymes, and (iii)
      the pineal content of serotonin and melatonin. Circadian rhythmicity of all the
      measured parameters was evaluated by the cosinor method. The levels of Aanat
      mRNA, AANAT enzymatic activity, and the pineal melatonin content changed during
      postembryonic development in a manner that was dependent on the season of hatch.
      Furthermore, the diurnal profile of Asmt mRNA was elevated during the light
      phase. In "winter" birds, the pattern and amplitude of the diurnal rhythm of
      accumulation of this transcript did not change with age, while in "summer" birds
      it increased in an age-related way. In contrast, the enzymatic activity of
      hydroxyindole-O-methyltransferase (HIOMT; encoded by the Asmt gene) did not
      change rhythmically, although it increased with age in a season-related way. In
      "winter" chickens, the pineal serotonin content was low, regardless of age, and
      did not change rhythmically, whereas in "summer" individuals the serotonin rhythm
      was already well established by day 2, with the amplitude increasing with age.
      These results confirm the existence of a "seasonal memory" operating within the
      chicken pineal gland, although the mechanism(s) underlying this phenomenon have
      yet to be characterized.

PMID- 23003335
TI  - p16(INK4a) /Ki-67 dual labelling as a marker for the presence of high-grade
      cancer cells or disease progression in urinary cytopathology.
AB  - OBJECTIVE: Overexpression of p16(INK4a) independent of the presence of E6-E7
      oncoproteins of high-risk papillomaviruses has been identified in bladder
      carcinoma in situ lesions with or without concurrent papillary or invasive high
      grade (HG) urothelial carcinoma. As p16(INK4a) and Ki-67 co-expression clearly
      indicates deregulation of the cell cycle, the aim of this study was to
      investigate the frequency of p16(INK4a) /Ki-67 dual labelling in urinary cytology
      samples. METHODS: Immunolabelling was performed in demounted, destained
      Papanicolaou slides after ThinPrep((r)) processing. A total of 84 urinary
      cytology samples (18 negative, 10 low grade, 19 atypical urothelial cells and 37
      high grade) were analysed for p16(INK4a) /Ki-67 co-expression. We assessed
      underlying urothelial malignancy with cystoscopy, histopathology and follow-up
      data in every case. RESULTS: Compared with raw histopathological results, p16
      (INK4a) /Ki-67 dual labelling was observed in 48 out of 55 (87.3%) HG lesions and
      in 11 out of 29 (37.9%) negative, papillary urothelial neoplasia of low malignant
      potential or low-grade carcinomas (P = 0.05). All cases with high-grade/malignant
      cytology were dual labelled. Sixteen out of 17 (94.1%) carcinoma in situ cases
      and eight out of 14 (57.1%) cases with atypical urothelial cells matching with HG
      lesions were dual labelled. Extended follow-up allowed three cases of progression
      to be diagnosed in dual-labelled cases with negative/low-grade cytology results
      after a 9- to 11-months delay. CONCLUSIONS: The data show that p16(INK4a) /Ki-67
      co-expression allows most HG cancer cells to be detected initially and in the
      follow-up period. Additional studies are needed in order to determine whether
      dual labelling can be used as a triage tool for atypical urothelial cells in the
      urine.

PMID- 23003336
TI  - Electronic detection of Drechslera sp. fungi in charentais melon ( Cucumis melo
      Naudin) using carbon-nanostructure-based sensors.
AB  - The development of chemical sensor technology in recent years has stimulated an
      interest regarding the use of characteristic volatiles and odors as a rapid and
      early indication of deterioration in fruit quality. The fungal infestation by 
      Drechslera  sp. in melons is a severe problem, and we demonstrate that electronic
      sensors based on carbon nanostructures are able to detect the presence of these
      fungi in melon. The responses of sensor conductance G and capacitance C at 27 kHz
      were measured and used to calculate their DeltaG and DeltaC variation over the
      full melon ripening process under shelf conditions with proliferation of 
      Drechslera  sp. fungi. The sensor response showed that these fungi can be
      electronically identified in charentais melon, constituting an effective and
      cheap test procedure to differentiate between infected and uninfected melon.

PMID- 23003337
TI  - Molecular mobility as an effective predictor of the physical stability of
      amorphous trehalose.
AB  - Amorphous trehalose was prepared by different methods, viz., freeze-drying, spray
      drying and dehydration of trehalose dihydrate. The different molecular
      relaxations were characterized by dynamic dielectric spectroscopy. The
      preparation method significantly affected the structural relaxation time and its
      temperature dependence in the glassy region. The order of activation energy for
      alpha-relaxation was spray-dried > freeze-dried > dehydrated. However, the
      secondary relaxation times remained essentially unaffected by the preparation
      method. Isothermal crystallization kinetics was studied at several temperatures
      above the glass transition temperature (T(g)). A linear correlation was observed
      between the crystallization time (inverse of crystallization rate constant) and
      the average alpha-relaxation time, suggesting a similar molecular origin for
      these two processes. There was also strong coupling of the crystallization onset
      time with global molecular mobility in the supercooled liquid region, enabling
      the development of predictive models. The observed experimental onset times were
      in excellent agreement with the predicted values at temperatures around and below
      T(g).

PMID- 23003338
TI  - Nursing power as viewed by nursing professionals.
AB  - BACKGROUND:   The concept of nursing power has not been extensively reported in
      the nursing literature. Power is an extremely abstract concept, making it
      difficult to define and study. However, when defined as the capacity to achieve
      goals, power becomes a significant resource in nursing. AIMS:   The aim of this
      study was to describe how nursing professionals perceive the level of nursing
      group power in public healthcare organizations. Additionally, the connections
      between the background variables and nursing group power were analysed. METHODS: 
      The participants in the study consisted of 289 Finnish nurses working in the
      specialist healthcare sector in Finland. The Sieloff-King Assessment of Group
      Outcome Attainment within Organizations(c) (SKAGOAO) instrument was utilized to
      assess the level of nursing group power within the selected organizations.
      FINDINGS:   According to the present study, nursing professionals rated the
      outcome attainment (mean, 1.93), as well as goals/outcome competency (mean,
      2.24), as very good. The position of nursing (mean, 2.55) as part of the
      healthcare service system was considered fairly respected. The role of nursing
      (mean, 2.54) was also considered to be at a good level. As regards to the
      actualization of power or outcome attainment capacity, respondents gave the
      lowest ratings to controlling the effects of environmental forces (mean, 2.75),
      resources (mean, 3.48), communication competency (mean, 3.00) and group
      supervisor's outcome attainment competency (mean, 2.87). Age, education, type of
      employment and work experience had an impact on how nursing group power was
      perceived. CONCLUSIONS:   The results of the present study indicated that the
      nurses perceived the lowest levels of group power in relation to the subscales of
      controlling the effects of environmental forces, resources, communication
      competency and group supervisor's outcome attainment competency.

PMID- 23003339
TI  - Affinity maturation of antiHER2 monoclonal antibody MIL5 using an epitope
      specific synthetic phage library by computational design.
AB  - Increased affinities mainly equal to improved biological efficacy in many cases.
      By now, display methods including phage library are widely exploited to obtain
      higher affinity antibodies. Traditional library methods mainly focus on
      complementary determining region mutagenesis, in which extensive screening of
      variant combinations as well as large library capacity is required to find higher
      affinity clones. In this study, based on the modeling 3D complex structure of
      antigen (HER2)-antibody (MIL5) complex, the key residues of contact surface were
      predicted and identified to guide the synthetic phage library design. Then,
      epitope-specific site-directed mutagenesis phage library comprised of MIL5_scFv
      mutants was constructed, from which a higher affinity single chain antibody
      (M5scFv_ph) was screened out. Following experimental results showed that the
      novel antibody M5scFv_ph retained superimposed epitope to the parent antibody
      MIL5_scFv, and possessed similar tumor growth inhibitory activity in vivo on
      ovarian carcinoma xenografts.

PMID- 23003340
TI  - Comparison of health care utilization: United States versus Canada.
AB  - OBJECTIVE: To compare health care utilization between Canadian and U.S.
      residents. DATA SOURCES: Nationally representative 2007 surveys from the Medical
      Expenditure Panel Survey for the United States and the Canadian Community Health
      Survey for Canada. STUDY DESIGN: We use descriptive and multivariate methods to
      examine differences in health care utilization rates for visits to medical
      providers, nurses, chiropractors, specialists, dentists, and overnight hospital
      stays, usual source of care, Pap smear tests, and mammograms. PRINCIPAL FINDINGS:
      The poor and less educated were more likely to utilize health care in Canada than
      in the United States. The differences were especially pronounced for having a
      usual source of care and for visits to providers, specialists, and dentists.
      Health care use for residents with high incomes and higher levels of education
      were not markedly different between the two countries and often higher for U.S
      residents. Foreign-born residents were more likely to use health care in Canada
      than in the United States. The descriptive results were confirmed in multivariate
      regressions. CONCLUSIONS: Given the magnitude of our results, the health
      insurance structure in Canada might have played an important role in improving
      access to care for subpopulations examined in this study.

PMID- 23003341
TI  - Do children recall the birth of a younger sibling? Implications for the study of
      childhood amnesia.
AB  - To establish the parameters of childhood amnesia, researchers often ask adults to
      recall events for which the exact date is known. One event of this kind is the
      birth of a sibling, but is this an event that children are likely to understand
      and encode at the time that it occurs? Here, we report the first examination of
      age-related changes in the content and accuracy of 2- to 5-year-old children's
      accounts of the recent birth of a sibling. The interview procedure we used was
      identical to that used in a prior study with adults, so we had the opportunity to
      compare children's recall with that of adults who were matched on age at the time
      of the birth. For both children and adults, the amount of information reported
      and the number of questions answered increased as a function of age at the time
      of the birth. Relative to children, adults reported more information and answered
      more questions. These findings suggest that the failure of adults to recall the
      birth of a younger sibling that occurred when they were very young may be due
      primarily to a failure to effectively encode the event in the first place.

PMID- 23003342
TI  - Development, in vitro and in vivo evaluation of novel injectable smart gels of
      azithromycin for chronic periodontitis.
AB  - Periodontitis is an inflammatory condition affecting teeth resulting in
      progressive destruction of periodontal ligaments, resorption of alveolar bone and
      loss of teeth. Treatment of periodontitis includes surgical and non surgical
      management. Systemic antibiotics are also used for the treatment of
      periodontitis. The aim of this research was to formulate smart gel system of
      azithromycin (AZT) and to evaluate in vitro and in vivo for non-surgical
      treatment of chronic periodontitis. Azithromycin dihydrate, used systemically in
      the treatment of periodontitis, was formulated into smart gels using
      biodegradable, thermosensitive polymer Pluronic(r) F-127 (PF-127) and Hydroxy
      Ethyl Cellulose (HEC) as copolymer. The prepared smart gels were evaluated for
      sterility, content uniformity, gelation temperature and time, syringeability,
      rheological behavior, in vitro diffusion and in vivo efficacy in human patients.
      The prepared smart gels were clear and transparent, sterile, thermoresponsive and
      injectable. Viscosity of gels increased with increase in concentration of
      polymer/co-polymer and also with temperature. They gelled in short response time
      below the body temperature. In vitro release studies showed controlled drug
      release which was influenced significantly by the properties and concentration of
      PF-127 and HEC. In vivo efficacy studies showed a significant improvement (p
      <0.001) in clinical parameters such as gingival index, probing pocket depth,
      clinical attachment level, bleeding index and plaque index. The developed
      azithromycin smart gel system is a novel approach for the treatment of chronic
      periodontitis since it reduces the dose and side effects, bypasses the usual
      surgical procedures and improves patient compliance.

PMID- 23003343
TI  - Specificity of the E1-E2-E3 enzymatic cascade for ubiquitin C-terminal sequences
      identified by phage display.
AB  - Ubiquitin (UB) is a protein modifier that regulates many essential cellular
      processes. To initiate protein modification by UB, the E1 enzyme activates the C
      terminal carboxylate of UB to launch its transfer through the E1-E2-E3 cascade
      onto target proteins. In this study, we used phage display to profile the
      specificity of the two human E1 enzymes, Ube1 and Uba6, toward the C-terminal
      sequence of UB ending with (71)LRLRGG(76). Phage selection revealed that while
      Arg72 of UB is absolutely required for E1 recognition, UB residues at positions
      71, 73, and 74 can be replaced with bulky aromatic side chains, and Gly75 of UB
      can be changed to Ser, Asp, and Asn for efficient E1 activation. We have thus
      found that the E1 enzymes have substantial promiscuity regarding the UB C
      terminal sequence. The UB variants from phage selection can also be transferred
      from E1 to E2 enzymes; however, they are blocked from further transfer to the E3
      enzymes. This suggests that the C-terminal sequence of UB is important for its
      discharge from E2 and subsequent transfer to E3. In addition, we observed that
      the Leu73Phe and Leu73Tyr single mutants of UB are resistant to cleavage by
      deubiquitinating enzymes (DUBs), although they can be assembled by the E1-E2-E3
      cascade into poly-UB chains, thus indicating differences in UB C-terminal
      specificities between the E1 and DUBs. Consequently these UB mutants may provide
      stability to UB polymers attached to cellular proteins and facilitate the
      elucidation of the biological signals encoded in the UB chains.

PMID- 23003344
TI  - Unexplored diversity and conservation potential of neotropical hot caves.
AB  - The term hot cave is used to describe some subterranean chambers in the
      Neotropics that are characterized by constantly high ambient temperatures
      generated by the body heat of high densities of certain bat species. Many of
      these species have limited geographic ranges, and some occur only in the hot-cave
      environment. In addition to the bats, the stable microclimate and abundant bat
      guano provides refuge and food for a high diversity of invertebrates. Hot caves
      have so far been described in the Caribbean and in a few isolated locations from
      Mexico to Brazil, although there is some evidence that similar caves may be
      present throughout the tropics. The existing literature suggests these poorly
      known ecosystems, with their unique combination of geomorphology and bat
      generated microclimate, are particularly sensitive to disturbance and face
      multiple threats from urbanization, agricultural development, mining, and
      tourism.

PMID- 23003345
TI  - A reporting guideline for clinical platelet transfusion studies from the BEST
      Collaborative.
AB  - BACKGROUND: A systematic review of randomized controlled trials and observational
      studies assessing platelet (PLT) transfusion therapy identified gaps in the
      descriptions of trial design, variables of the PLT products transfused, and
      outcomes. We aimed to systematically develop a reporting guideline to aid in
      designing, reporting, and critiquing PLT trials. STUDY DESIGN AND METHODS: With
      the use of expert opinion, a preliminary checklist of 23 items was created. The
      Delphi method, an iterative forecasting method, was used to achieve consensus
      among experts to systematically improve upon the preliminary checklist. Items
      were ranked for inclusion using a 7-point Likert scale from "definitely should
      not" to "very important to" include. Criteria were established a priori based on
      the mean score: at least 5.5 accept, 2.6 to 5.4 intermediate, and not more than
      2.5 eliminate. Intermediate items were edited and sent out in subsequent rounds
      for review. Three rounds were undertaken to determine the final checklist.
      RESULTS: Initially 33 experts participated, decreasing to 25 by the third round.
      The preliminary checklist consisted of 23 items spread over four sections:
      methods and intervention, PLT-specific outcomes, PLT-specific results, and PLT
      specific adverse events. After three rounds of the Delphi method, the checklist
      was expanded and refined to include 30 items. The final checklist was further
      enhanced by adding an explanatory guide. CONCLUSION: Use of the Delphi method was
      successful in finding consensus on items to include in reports of a clinical PLT
      transfusion study. The final checklist and explanatory guide will be useful for
      authors and editors to improve the reporting of PLT transfusion trials.

PMID- 23003346
TI  - Hemodynamic changes at the saphenofemoral junction during the application of a
      below-knee graduated compression stocking.
AB  - BACKGROUND: It is strongly recommended that patients wear compression after foam
      sclerotherapy, but pulling up a stocking may inadvertently flush foam into the
      femoral vein, which may increase the risk of systemic side effects and reduce
      great saphenous vein (GSV) occlusion rates. OBJECTIVE: The hypothesis was that a
      stocking pull-up maneuver would increase flow in the GSV. The aim was to quantify
      this using duplex ultrasound. METHODS AND MATERIALS: Twelve consecutive patients
      with primary varicose veins were studied. A below-knee 23- to 32-mmHg graduated
      elastic compression stocking was placed over the foot, leaving a cuff of
      redundant stocking around the ankle. Duplex ultrasound over the saphenofemoral
      junction was used to measure peak velocity (PV) and volume flow (VF) before and
      while the stocking was being pulled up. RESULTS: The pull-up maneuver caused a
      median 17.7 times increase in PV (interquartile range (IQR) 14.2-23.9), from 7.6
      cm/seconds (IQR 6.4-9.8 cm/seconds) to 150.5 cm/seconds (IQR 110-187 cm/seconds)
      and a 9.4 times increase in VF (IQR 7.7-10.3), from 50.9 mL/minutes (IQR 33.8
      78.9 mL/minutes) to 458.7 mL/minutes (IQR 292.1-593 mL/minutes) (p = .002).
      CONCLUSION: A stocking causes significant hemodynamic changes within the GSV.
      These forces could be avoided by the partial application of a stocking to knee
      level before foam injection. Further work may establish the implication of these
      findings in patients treated with foam sclerotherapy.

PMID- 23003560
TI  - The utility of post-concussion neuropsychological data in identifying cognitive
      change following sports-related MTBI in the absence of baseline data.
AB  - Neuropsychological tests have become commonplace in the assessment of sports
      related concussion. Typically, post-injury test data are compared to pre-injury
      "baselines." Baseline testing can be expensive and logistically challenging, yet
      the usefulness of neuropsychological baseline testing has not been tested
      empirically. This paper examines the extent to which baseline testing is useful
      for detecting neurocognitive deficits following sports concussion in a college
      age population. A total of 223 collegiate athletes from multiple sports who
      sustained concussions and had both baseline and post-injury testing using
      Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) were included
      in the study. Reliable change (RC) in scores was determined by two approaches,
      the Jacobson and Truax (JT) and the Gulliksen-Lord-Novick (GLN) methods. The 90%
      confidence interval was used for both. Classification using these methods was
      compared to standard normative methods that compared post-concussion performance
      to baseline population means. Agreement between reliable change and normative
      methods was examined using Cohen's Kappa scores to determine whether post-injury
      scores alone could identify reliable cognitive decline. Mean time from concussion
      to post-injury testing was 3.40 days. The percentage of athletes who declined
      when using the JT method was similar to the percentage that would be expected to
      decline due to chance alone. Although the GLN and JT methods demonstrated
      moderate to substantial agreement, the GLN method consistently identified more
      cognitively compromised athletes than the JT method. Post-injury scores alone
      identified a significant majority of athletes with a reliable decline on ImPACT.
      Although preliminary and in need of replication across age groups and
      instruments, these findings suggest that the majority of collegiate athletes who
      experience clinically meaningful post-concussion cognitive decline can be
      identified without baseline data.

PMID- 23003561
TI  - Observation on the ion association equilibria in NaNO3 droplets using micro-Raman
      spectroscopy.
AB  - Ion association ratios as a function of concentration were estimated in single
      NaNO(3) droplets (5-60 MUm) on a polytetrafluoroethylene (PTFE) substrate with
      molar water-to-solute ratios (WSRs) of 0.8-28 and bulk NaNO(3) solutions with
      WSRs of 35-200 by combining micro-Raman spectroscopy and component band analysis.
      Concentrations of the NaNO(3) droplets were accurately controlled by adjusting
      relative humidity (RH) in a sample chamber. As the WSRs decreased from 200 to
      0.8, symmetric stretching band (nu(1)-NO(3)(-)) was observed to shift from 1047
      to 1058 cm(-1) along with a change in full width at half-maximum (fwhm) from ~10
      to ~16 cm(-1), indicative of formation of ion pairs with different structures.
      Through the component band analysis of the nu(1)-NO(3)(-) band, five bands
      centered at 1040.0, 1042.9, 1048.5, 1053.5, and 1057.0 cm(-1) were identified and
      assigned to coupled wagging modes of water molecules hydrated with nitrate ions,
      free hydrated nitrate anions, solvent-shared ion pairs (SIPs), contact ion pairs
      (CIPs), and the complex ion aggregates (CIAs), respectively. There were large
      amounts of SIPs and CIPs in dilute NaNO(3) solution even at an extremely low
      concentration (WSR ~ 200), and each accounted for 50% and 20% of total nitrate
      species, respectively. This finding is in good agreement with earlier reported
      observations. In the dilute solutions (45 < WSR < 200), there is the same amount
      of free hydrated ions transformed into SIPs as that of SIPs transformed into
      CIPs. As a result, the overall amount of SIPs remained unchanged over the
      concentration range. With a decrease in WSR from 45 to 0.8, the amounts of SIPs
      and free solvated NO(3)(-) ions kept decreasing, whereas the amount of CIPs rose
      to a maximum at WSR = 7 and then fell with a further decreasing WSR. Formation of
      CIAs started at WSR ~ 45, and its amount continuously increased as the WSR is
      further reduced to 0.8. The effect of temperature on ion association structure in
      the NaNO(3) droplets was also studied in the present work. An increase in
      temperature promoted formation of both CIPs and CIAs, and the latter was more
      pronounced. At 80  degrees C, the most concentrated NaNO(3) droplets had a WSR
      approximately equal to 0.12 and were in amorphous state with cations and anions
      aggregated in a complicated manner, highly similar to ionic liquid.

PMID- 23003562
TI  - Umbilical cord presentation after use of a trans-cervical balloon catheter.
AB  - AIM: To examine the incidence of umbilical cord presentation, including cord
      prolapse (UCP) and cord descent (UCD), after the use of a trans-cervical balloon
      catheter (TCBC), such as a Foley catheter and a metreurynter, for the induction
      of labor (IOL). METHODS: A retrospective medical chart review was conducted,
      focusing on the occurrence of UCP and UCD in 800 women who underwent IOL with a
      TCBC at five hospitals during the study period (2008-2009 for two hospitals and
      2006-2009 for three hospitals). The five hospitals had a total of 8245 deliveries
      during the study period. UCP and UCD were defined as the descent of the umbilical
      cord in advance of the presenting fetal part in the presence and absence of
      rupture of fetal membranes, respectively. RESULTS: The frequency of IOL using a
      TCBC with 70-250 mL of saline varied among the five hospitals from 4.9% to 18.8%
      (mean +/- SD, 10.7 +/- 5.0%). UCP and UCD occurred in two and four women,
      respectively, with the frequency of cord presentation varying among the hospitals
      from 0.0% to 1.8% (mean +/- SD, 0.9 +/- 0.9%); the cord presentation was
      significantly more likely to occur when 180-250 mL of saline was used, compared
      with when 70-150 mL of saline was used (8.2% [5/61] vs 0.15% [1/662], P <
      0.0001). A change in the presenting fetal body part also occurred in 0.5% (4/800)
      of the women. CONCLUSION: The use of a TCBC with 180-250 mL of saline increases
      the risk of cord presentation.

PMID- 23003564
TI  - In vitro assessment of epithelial electrical resistance in human esophageal and
      jejunal mucosae and in Caco-2 cell layers.
AB  - OBJECTIVE: There is a need for a technique allowing studies of human mucosal
      specimens collected during different clinical conditions. This study elucidates
      if square wave pulse analysis discriminates between epithelial and transmural
      electrical resistance and if there is an association with transepithelial
      permeability of molecular probes. METHODS: Mucosae from esophagus (surgical
      resections: n = 14; endoscopic biopsies: n = 15) and jejunum (n = 12) and Caco-2
      cell monolayers were investigated in Ussing chambers. Transmural and epithelial
      electrical resistance were recorded by the use of standardized current pulses.
      Permeability was assessed using two fluorescein-labeled probes (weight 376 and
      4000 Da). RESULTS: Baseline epithelial electrical resistance was higher in
      esophageal mucosa (~280 Omega*cm(2)), than in jejunal (~10 Omega*cm(2)) and Caco
      2 cells (~140 Omega*cm(2)). The subepithelial contribution to the transmural
      resistance was higher in jejunal preparations (+88%) and Caco-2 cells (+75%),
      than in esophageal (+30%). During hypoxia the subepithelial resistance was
      unchanged, whereas the epithelial resistance decreased significantly in jejunal
      mucosa and Caco-2 cells. These findings coincided with increased transepithelial
      probe permeability and signs of disturbed morphology. Esophageal epithelia were
      resistant to hypoxia. However, exposure to deoxycholic acid and trypsin abolished
      the esophageal epithelial resistance and increased probe permeability. Endoscopic
      esophageal biopsies from patients with erosive reflux disease exhibited
      significantly lower epithelial resistance and higher current than healthy
      subjects. CONCLUSION: Square wave pulse analysis in Ussing chambers is suitable
      for assessment of epithelial electrical resistance that can reflect
      transepithelial permeability of molecular probes with known size. Moreover, the
      technique discriminated between healthy and reflux-diseased esophageal mucosal
      biopsies.

PMID- 23003563
TI  - Spectroscopic and functional characterization of iron-bound forms of Azotobacter
      vinelandii (Nif)IscA.
AB  - The ability of Azotobacter vinelandii(Nif)IscA to bind Fe has been investigated
      to assess the role of Fe-bound forms in NIF-specific Fe-S cluster biogenesis.
      (Nif)IscA is shown to bind one Fe(III) or one Fe(II) per homodimer and the
      spectroscopic and redox properties of both the Fe(III)- and Fe(II)-bound forms
      have been characterized using the UV-visible absorption, circular dichroism, and
      variable-temperature magnetic circular dichroism, electron paramagnetic
      resonance, Mossbauer and resonance Raman spectroscopies. The results reveal a
      rhombic intermediate-spin (S = 3/2) Fe(III) center (E/D = 0.33, D = 3.5 +/- 1.5
      cm(-1)) that is most likely 5-coordinate with two or three cysteinate ligands and
      a rhombic high spin (S = 2) Fe(II) center (E/D = 0.28, D = 7.6 cm(-1)) with
      properties similar to reduced rubredoxins or rubredoxin variants with three
      cysteinate and one or two oxygenic ligands. Iron-bound (Nif)IscA undergoes
      reversible redox cycling between the Fe(III)/Fe(II) forms with a midpoint
      potential of +36 +/- 15 mV at pH 7.8 (versus NHE). l-Cysteine is effective in
      mediating release of free Fe(II) from both the Fe(II)- and Fe(III)-bound forms of
      (Nif)IscA. Fe(III)-bound (Nif)IscA was also shown to be a competent iron source
      for in vitro NifS-mediated [2Fe-2S] cluster assembly on the N-terminal domain of
      NifU, but the reaction occurs via cysteine-mediated release of free Fe(II) rather
      than direct iron transfer. The proposed roles of A-type proteins in storing Fe
      under aerobic growth conditions and serving as iron donors for cluster assembly
      on U-type scaffold proteins or maturation of biological [4Fe-4S] centers are
      discussed in light of these results.

PMID- 23003565
TI  - Single quantum dot based nanosensor for renin assay.
AB  - Evaluation of plasma renin activity is essential to the assessment of renin
      related diseases such as hypertension, congestive heart failure, and cancers.
      Here, we develop a single quantum dot (QD) based nanosensor for sensitive
      detection of renin activity. This single-QD-based nanosensor consists of a
      streptavidin-coated QD and multiple biotinylated and Cy5-labeled peptide
      substrates, which form a QD/substrate/Cy5 complex where fluorescence resonance
      energy transfer (FRET) occurs with the QD as the donor and Cy5 as the acceptor.
      The presence of renin leads to the cleavage of the substrate and the separation
      of Cy5 from the QD and consequently the decrease of FRET efficiency and the
      reduction of Cy5 counts. Through the measurement of Cy5 counts by total internal
      reflection fluorescence (TIRF) microscopy, the renin activity can be
      quantitatively evaluated at the single-molecule level. This single-QD-based
      nanosensor can measure not only the renin concentration, but also the enzymatic
      velocity and the Michaelis-Menten kinetic parameters, and has significant
      advantages of simplicity, low cost with minimum sample consumption, and high
      sensitivity with a detection limit of 25 pM. This single-QD-based nanosensor
      might be further applied to monitor a variety of important enzymatic biomarkers
      such as kinases and endonuleases.

PMID- 23003566
TI  - Reactivity of the anionic diphosphorus complex [Mo2Cp2(MU-PCy2)(CO)2(MU
      kappa2:kappa2-P2)]- toward ER3X electrophiles (E = C to Pb): insights into the
      multisite donor ability and dynamics of the P2 ligand.
AB  - The Li(+) salt of the unsaturated anion [Mo(2)Cp(2)(MU-PCy(2))(MU-CO)(2)](-)
      reacted with P(4) in tetrahydrofuran at room temperature to give the title
      complex. This fluxional anion reacted with MeI and ClCH(2)Ph to give the
      diphosphenyl complexes [Mo(2)Cp(2)(MU-kappa(2):kappa(2)-P(2)CH(2)R)(MU
      PCy(2))(CO)(2)] (R = H, Ph), with the incoming electrophile being attached at the
      basal P atom of the Mo(2)P(2) tetrahedron via the lone electron pair (P-P-CH(3) =
      122.8(1)(o)). In contrast, reactions with ClER(3) (ER(3) = GePh(3), SnPh(3),
      PbMe(3), PbPh(3)) gave neutral complexes [Mo(2)Cp(2)(MU-kappa(2):kappa(2)
      P(2)ER(3))(MU-PCy(2))(CO)(2)] having the incoming electrophile attached at the
      basal P atom but defining an acute P-P-E angle close to 90 degrees  with
      elongated P-P lengths of ca. 2.20 A. These complexes undergo an easy fluxional
      process involving an exchange of the ER(3) group between the P atoms that could
      be properly modeled through DFT calculations, and some of them displayed minor
      isomers in solution. Their structure could be rationalized as derived from the
      interaction of the electrophile with high-energy orbitals of the anion having
      both sigma(Mo-P) and pi(P-P) bonding character. Reaction with BrSiMe(3) gave
      instead the agostic phosphenyl complex [Mo(2)Cp(2)(MU-kappa(2):kappa(1),eta(2)
      HP(2))(MU-PCy(2))(CO)(2)], formally derived from the attachment of a proton to a
      basal Mo-P edge of the anion (computed length 2.810 A) and displaying an
      unusually low P-H coupling of 4 Hz. A similar structure, with the agostic H atom
      replaced with SnH(3), was found to be a satisfactory model for the minor isomer
      of the tin compound and represents a third and unprecedented coordination mode of
      the diphosphorus ligand. The agostic complex undergoes a fluxional process
      involving the intermediacy of the nonagostic isomer [Mo(2)Cp(2)(MU
      kappa(2):kappa(2)-P(2)H)(MU-PCy(2))(CO)(2)], which was computed to display a
      geometry comparable to the major isomers of the ER(3) compounds (P-P = 2.183 A; P
      P-H = 81.7 degrees ).

PMID- 23003567
TI  - Twice daily melatonin peaks in Siberian but not Syrian hamsters under 24 h
      light:dark:light:dark cycles.
AB  - The daily pattern of blood-borne melatonin varies seasonally under the control of
      a multi-oscillator circadian pacemaker. Here we examine patterns of melatonin
      secretion and locomotor activity in Siberian and Syrian hamsters entrained to
      bimodal LDLD8:4:8:4 and LD20:4 lighting schedules that facilitate novel temporal
      arrangements of component circadian oscillators. Under LDLD, both species
      robustly bifurcated wheel-running activity in distinct day scotophase (DS) and
      night scotophase (NS) bouts. Siberian hamsters displayed significant melatonin
      increases during each scotophase in LDLD, and in the single daily scotophase of
      LD20:4. The bimodal melatonin secretion pattern persisted in acutely extended 16
      h scotophases. Syrian hamsters, in contrast, showed no significant increases in
      plasma melatonin during either scotophase of LDLD8:4:8:4 or in LD20:4. In this
      species, detectable levels were observed only when the DS of LDLD was acutely
      extended to yield 16 h of darkness. Established species differences in the phase
      lag of nocturnal melatonin secretion relative to activity onset may underlie the
      above contrast: In non-bifurcated entrainment to 24 h LD cycles, Siberian
      hamsters show increased melatonin secretion within ~ 2 h after activity onset,
      whereas in Syrian hamsters, detectable melatonin secretion phase lags activity
      onset and the L/D transition by at least 4 h. The present results provide new
      evidence indicating multi-oscillator regulation of the waveform of melatonin
      secretion, specifically, the circadian control of the onset, offset and duration
      of nocturnal secretion.

PMID- 23003568
TI  - GuideToPharmacology.org--an update.

PMID- 23003571
TI  - Histological and fine needle aspiration cytological features of Hashimoto
      thyroditis-associated 'angiomatoid' papillary thyroid carcinoma.

PMID- 23003570
TI  - Pigmented-MDCK (P-MDCK) cell line with tunable melanin expression: an in vitro
      model for the outer blood-retinal barrier.
AB  - Retinal pigment epithelium, which forms the outer blood-retinal barrier, is a
      critical barrier for transport of drugs to the retina. The purpose of this study
      was to develop a pigmented MDCK (P-MDCK) cell line as a rapidly established in
      vitro model for the outer blood-retinal barrier to assess the influence of
      melanin pigment on solute permeability. A melanin synthesizing P-MDCK cell line
      was developed by lentiviral transduction of human tyrosinase and p-protein genes
      in MDCK (NBL-2) cells. Melanin content, tyrosinase activity (conversion of L-dopa
      to dopachrome), and transepithelial electrical resistance (TEER) were measured.
      Expression of tyrosinase protein and p-protein in P-MDCK cells was confirmed by
      confocal microscopy. Effect of l-tyrosine (0 to 2 mM) in culture medium on
      melanin synthesis in P-MDCK cells was evaluated. Cell uptake and transepithelial
      transport of pigment-binding chloroquine (Log D = 1.59) and a negative control
      salicylic acid (Log D = -1.14) were investigated. P-MDCK cells expressed
      tyrosinase and p-protein. Tyrosinase activity was 4.5-fold higher in P-MDCK cells
      compared to wild type MDCK cells. The transepithelial electrical resistance
      stabilized by day 4 in both cell types, with the TEER being 958 +/- 33 and 964 +/
      58 Omega.cm(2) for P-MDCK and wild type cells, respectively. Melanin content in
      P-MDCK cells depended on the concentration of l-tyrosine in culture medium, and
      increased from 3 to 54 MUg/mg protein with an increase in l-tyrosine content from
      0 to 2 mM. When the cells were grown in 2 mM l-tyrosine, uptake of chloroquine
      was 2.3-fold higher and the transepithelial transport was 2.2-fold lower in P
      MDCK cells when compared to wild type MDCK cells. No significant difference was
      observed for both cell uptake and transport of salicylic acid. We developed a P
      MDCK cell line with tunable melanin synthesis as a rapidly developing surrogate
      for retinal pigment epithelium.

PMID- 23003572
TI  - Molecular characterization of a novel arylesterase from the wine-associated
      acetic acid bacterium Gluconobacter oxidans 621H.
AB  - An arylesterase from the wine-making acetic acid bacterium, Gluconobacter
      oxidans, was cloned and expressed into Escherichia coli. The soluble 76.8 kDa
      dimeric enzyme obtained, Est0881, was purified in only two steps with a 3.1-fold
      purification, 43% recovery, and a specific activity of 214 U/mg for the
      hydrolysis of p-nitrophenyl acetate. The optimum pH and temperature were 7.0 and
      40  degrees C, respectively. The substrate specificity of this arylesterase was
      higher toward short chain p-nitrophenyl esters (C(2) to C(4)) and also toward
      aromatic esters, such as phenyl acetate. The deduced amino acid sequence shares
      high identity with esterases of the HSL family. The inhibition results obtained
      showed that the enzyme was a serine esterase, belonging to the A-esterases
      (arylesterases) and contains a catalytic triad composed of Ser163, Asp263, and
      His293 in the active site. Est0881 retained significant activity under conditions
      simulating those of wine-making (75% activity at 20% ethanol), making it a
      promising biocatalyst for modulating the final aroma of wine.

PMID- 23003573
TI  - DNA methylation of the filaggrin gene adds to the risk of eczema associated with
      loss-of-function variants.
AB  - BACKGROUND: Loss-of-function variants within the filaggrin gene (FLG) are
      associated with a dysfunctional skin barrier that contributes to the development
      of eczema. Epigenetic modifications, such as DNA methylation, are genetic
      regulatory mechanisms that modulate gene expression without changing the DNA
      sequence. OBJECTIVES: To investigate whether genetic variants and adjacent
      differential DNA methylation within the FLG gene synergistically act on the
      development of eczema. METHODS: A subsample (n = 245, only females aged 18 years)
      of the Isle of Wight birth cohort participants (n = 1456) had available
      information for FLG variants R501X, 2282del4 and S3247X and DNA methylation
      levels for 10 CpG sites within the FLG gene. Log-binomial regression was used to
      estimate the risk ratios (RRs) of eczema associated with FLG variants at
      different methylation levels. RESULTS: The period prevalence of eczema was 15.2%
      at age 18 years and 9.0% of participants were carriers (heterozygous) of FLG
      variants. Of the 10 CpG sites spanning the genomic region of FLG, methylation
      levels of CpG site 'cg07548383' showed a significant interaction with FLG
      sequence variants on the risk for eczema. At 86% methylation level, filaggrin
      haploinsufficient individuals had a 5.48-fold increased risk of eczema when
      compared to those with wild type FLG genotype (P-value = 0.0008). CONCLUSIONS:
      Our novel results indicated that the association between FLG loss-of-function
      variants and eczema is modulated by DNA methylation. Simultaneously assessing the
      joint effect of genetic and epigenetic factors within the FLG gene further
      highlights the importance of this genomic region for eczema manifestation.

PMID- 23003574
TI  - Approaches to reduce urinary tract injury during management of placenta accreta,
      increta, and percreta: a systematic review.
AB  - OBJECTIVE: A systematic review of the literature was conducted to answer the
      following question: are there enhancements to standard peripartum hysterectomy
      technique that minimize unintentional urinary tract (UT) injury in pregnancies
      complicated by invasive placental attachment (INPLAT)? METHODS: A PubMed search
      of English language articles on INPLAT published by June 2010 was conducted. Data
      regarding the following parameters was required for inclusion in the quantitative
      analysis of the review's objective: (1) type of INPLAT, (2) details pertaining to
      medical and surgical management of INPLAT, and (3) complications, if any,
      associated with management. An attempt was made to identify approaches that may
      lower the risk of unintentional UT injury. RESULTS: Most cases (285 of 292) were
      managed by hysterectomy. There were 83 (29%) cases of unintentional UT injury.
      Antenatal diagnosis of INPLAT lowered the rate of UT injury (39% vs. 63%; P =
      0.04). Information regarding surgical technique or medical management was
      available for 90 cases; 14 of these underwent a standard hysterectomy technique.
      Methotrexate treatment and 11 modifications of the surgical technique were
      associated with 16% unintentional UT injury rate as opposed to 57% for standard
      hysterectomy (P = 0.002). The use of ureteral stents reduced risk of urologic
      injury (P = 0.01). Multiple logistic regression analysis identified antenatal
      diagnosis as the significant predictor of an intact UT. CONCLUSIONS: Antenatal
      diagnosis of INPLAT is paramount to minimize UT injury. Utilization of management
      modifications identified in this review may reduce urologic injury due to INPLAT.

PMID- 23003575
TI  - Being perceived as a 'visitor' in the nursing staff's working arena--the
      involvement of relatives in daily caring activities in nursing homes in an urban
      community in Sweden.
AB  - BACKGROUND: It is both complex and difficult for relatives when a loved one moves
      into a nursing home and many relatives are not prepared for the realities these
      new situations entail. Little attention has been paid to scrutinising the
      involvement of relatives in patient care, particularly in relation to the
      structures and routines of nursing homes or to the staff's reasoning concerning
      their involvement. AIM: To describe, from a gender perspective, how nursing
      staff's routines and reasoning act to condition the involvement of relatives in
      nursing homes. METHODS: Focused ethnographic fieldwork was conducted in a medium
      sized urban community in central Sweden in three different nursing homes.
      RESULTS: The nursing staff assigns a certain code of conduct to all relatives
      they perceived as 'visitors' in their working arena. This code of conduct was
      related to the routines and subcultures existing among the nursing staff and
      stemmed from a division of labour; the underlying concept of 'visitor'
      predetermined the potential for relatives' involvement. This involvement is
      explicitly related to the general gendered characteristics that exist in the
      nursing staff's perception of the relatives. DISCUSSION: The study's limitations
      are primarily concerned with shortcomings associated with a research presence
      during the fieldwork. The discussion focuses on the dimensions of power
      structures observed in the nursing home routines and the staff's reasoning based
      on their gendered assumptions. We argue that it is important to develop
      mechanisms that provide opportunities for nursing staff in elderly care to
      reflect on these structures without downplaying the excellent care they provide.
      We stress the importance of further exploring these issues concerning relatives
      and their involvement in nursing homes to facilitate the transition from informal
      caregiver to 'visitor'.

PMID- 23003577
TI  - Supra- and nanocrystallinity: specific properties related to crystal growth
      mechanisms and nanocrystallinity.
AB  - The natural arrangement of atoms or nanocrystals either in well-defined
      assemblies or in a disordered fashion induces changes in their physical
      properties. For example, diamond and graphite show marked differences in their
      physical properties though both are composed of carbon atoms. Natural colloidal
      crystals have existed on earth for billions of years. Very interestingly, these
      colloidal crystals are made of a fixed number of polyhedral magnetite particles
      uniform in size. Hence, opals formed of assemblies of silicate particles in the
      micrometer size range exhibit interesting intrinsic optical properties. A
      colorless opal is composed of disordered particles, but changes in size
      segregation within the self-ordered silica particles can lead to distinct color
      changes and patterning.  In this Account, we rationalize two simultaneous
      supracrystal growth processes that occur under saturated conditions, which form
      both well-defined 3D superlattices at the air-liquid interface and precipitated
      3D assemblies with well-defined shapes. The growth processes of these colloidal
      crystals, called super- or supracrystals, markedly change the mechanical
      properties of these assemblies and induce the crystallinity segregation of
      nanocrystals. Therefore, single domain nanocrystals are the primary basis in the
      formation of these supracrystals, while multiply twinned particles (MTPs) and
      polycrystals remain dispersed within the colloidal suspension. Nanoindentation
      measurements show a drop in the Young's moduli for interfacial supracrystals in
      comparison with the precipitated supracrystals. In addition, the value of the
      Young's modulus changes markedly with the supracrystal growth mechanism. Using
      scanning tunneling microscopy/spectroscopy, we successfully imaged very thick
      supracrystals (from 200 nm up to a few micrometers) with remarkable conductance
      homogeneity and showed electronic fingerprints of isolated nanocrystals. This
      discovery of nanocrystal fingerprints within supracrystals could lead to
      promising applications in nanotechnology.

PMID- 23003576
TI  - In vitro and in vivo properties differ among liquid intravenous immunoglobulin
      preparations.
AB  - OBJECTIVE: To compare in vitro and in vivo biological and biochemical properties
      of five liquid intravenous immunoglobulin (IVIg) preparations licensed for
      therapeutic use in Europe. METHODS: ClairYg((r)) was compared in a blinded manner
      to four other liquid IVIg preparations licensed in Europe (Octagam((r)) ,
      Kiovig((r)) , Gamunex((r)) , Privigen((r)) ). Three batches of each preparation
      were tested, except for the IgG repertoires and the animal model. RESULTS: Levels
      of anti-A and anti-B antibodies were lower in ClairYg((r)) (0.11/0.11) relative
      to a positive EDQM standard and Octagam((r)) (0.11/0.08) than in other
      preparations (0.33-0.69/0.42-0.46). IgG in ClairYg((r)) recognized 365 and 416
      protein spots in HEp-2 cell and Escherichia coli protein extracts vs. 230-330 and
      402-842 protein spots, respectively, for IgG in other preparations. IgA content
      (301 vs. 165-820 ng/mg of IgG), Factor XI and Factor XII antigen (0.46 vs. 0.85
      2.40 mU/mg of IgG and 7.8 vs. 20.0-46.2 lU/mg of IgG) C1q binding (0.42 vs. 0.67
      1.89 arbitrary units) and C5a uptake (0.41 vs. 0.45-0.66% of activation) were
      lower in ClairYg((r)) than in other preparations. Finally, intravenous infusion
      of ClairYg((r)) , Gamunex((r)) and Privigen((r)) had no major effect on arterial
      blood pressure in spontaneously hypertensive rats. CONCLUSIONS: Our results
      evidence some differences in the biological and biochemical properties among
      licensed liquid IVIg preparations.

PMID- 23003578
TI  - Edge states and topological phases in one-dimensional optical superlattices.
AB  - We show that one-dimensional quasiperiodic optical lattice systems can exhibit
      edge states and topological phases which are generally believed to appear in two
      dimensional systems. When the Fermi energy lies in gaps, the Fermi system on the
      optical superlattice is a topological insulator characterized by a nonzero
      topological invariant. The topological nature can be revealed by observing the
      density profile of a trapped fermion system, which displays plateaus with their
      positions uniquely determined by the ration of wavelengths of the bichromatic
      optical lattice. The butterflylike spectrum of the superlattice system can be
      also determined from the finite-temperature density profiles of the trapped
      fermion system. This finding opens an alternative avenue to study the topological
      phases and Hofstadter-like spectrum in one-dimensional optical lattices.

PMID- 23003569
TI  - Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential
      therapeutic strategies.
AB  - Traumatic brain injury (TBI) is a major health and socioeconomic problem
      throughout the world. It is a complicated pathological process that consists of
      primary insults and a secondary insult characterized by a set of biochemical
      cascades. The imbalance between a higher energy demand for repair of cell damage
      and decreased energy production led by mitochondrial dysfunction aggravates cell
      damage. At the cellular level, the main cause of the secondary deleterious
      cascades is cell damage that is centred in the mitochondria. Excitotoxicity,
      Ca(2+)  overload, reactive oxygen species (ROS), Bcl-2 family, caspases and
      apoptosis inducing factor (AIF) are the main participants in mitochondria-centred
      cell damage following TBI. Some preclinical and clinical results of mitochondria
      targeted therapy show promise. Mitochondria- targeted multipotential therapeutic
      strategies offer new hope for the successful treatment of TBI and other acute
      brain injuries.

PMID- 23003579
TI  - Are dynamical quantum jumps detector dependent?
AB  - Dynamical quantum jumps were initially conceived by Bohr as objective events
      associated with the emission of a light quantum by an atom. Since the early 1990s
      they have come to be understood as being associated rather with the detection of
      a photon by a measurement device, and that different detection schemes result in
      different types of jumps (or diffusion). Here we propose experimental tests to
      rigorously prove the detector dependence of the stochastic evolution of an
      individual atom. The tests involve no special preparation of the atom or field,
      and the required efficiency can be as low as eta~58%.

PMID- 23003580
TI  - Toward global quantum communication: beam wandering preserves nonclassicality.
AB  - Tap-proof long-distance quantum communication requires a deep understanding of
      the strong losses in transmission channels. Here we provide a rigorous treatment
      of the effects of beam wandering, one of the leading disturbances in atmospheric
      channels, on the quantum properties of light. From first principles we derive the
      probability distribution of the beam transmissivity, with the aim to completely
      characterize the quantum state of light. It turns out that beam wandering may
      preserve nonclassical effects, such as entanglement, quadrature and photon number
      squeezing, much better than a standard attenuating channel of the same losses.

PMID- 23003581
TI  - Designer spin pseudomolecule implemented with trapped ions in a magnetic
      gradient.
AB  - We report on the experimental investigation of an individual pseudomolecule using
      trapped ions with adjustable magnetically induced J-type coupling between spin
      states. Resonances of individual spins are well separated and are addressed with
      high fidelity. Quantum gates are carried out using microwave radiation in the
      presence of thermal excitation of the pseudomolecule's vibrations. Demonstrating
      controlled-NOT gates between non-nearest neighbors serves as a proof-of-principle
      of a quantum bus employing a spin chain. Combining advantageous features of
      nuclear magnetic resonance experiments and trapped ions, respectively, opens up a
      new avenue toward scalable quantum information processing.

PMID- 23003582
TI  - Role of hidden slow degrees of freedom in the fluctuation theorem.
AB  - The validity of the fluctuation theorem for entropy production as deduced from
      the observation of trajectories implicitly requires that all slow degrees of
      freedom are accessible. We experimentally investigate the role of hidden slow
      degrees of freedom in a system of two magnetically coupled driven colloidal
      particles. The apparent entropy production based on the observation of just one
      particle obeys a fluctuation theorem-like symmetry with a slope of 1 in the short
      time limit. For longer times, we find a constant slope, but different from 1. We
      present theoretical arguments for a generic linear behavior both for small and
      large apparent entropy production but not necessarily throughout. By fine-tuning
      experimental parameters, such an intermediate nonlinear behavior can indeed be
      recovered in our system as well.

PMID- 23003583
TI  - Detecting chameleon dark energy via an electrostatic analogy.
AB  - The late-time accelerated expansion of the Universe could be caused by a scalar
      field that is screened on small scales, as in the case of chameleon or symmetron
      scenarios. We present an analogy between such scalar fields and electrostatics,
      which allows calculation of the field profile for general extended bodies.
      Interestingly, the field demonstrates a "lightning rod" effect, where it becomes
      enhanced near the ends of a pointed or elongated object. Drawing from this
      correspondence, we show that nonspherical test bodies immersed in a background
      field will experience a net torque caused by the scalar field. This effect, with
      no counterpart in the gravitational case, can be potentially tested in future
      experiments.

PMID- 23003584
TI  - High energy neutrinos from the Fermi bubbles.
AB  - Recently the Fermi-LAT data have revealed two gamma-ray emitting bubble-shaped
      structures at the Galactic center. If the observed gamma rays have hadronic
      origin (collisions of accelerated protons), the bubbles must emit high energy
      neutrinos as well. This new, Galactic, neutrino flux should trace the gamma-ray
      emission in spectrum and spatial extent. Its highest energy part, above 20-50
      TeV, is observable at a kilometer-scale detector in the northern hemisphere, such
      as the planned KM3NeT, while interesting constraints on it could be obtained by
      the IceCube Neutrino Observatory at the South Pole. The detection or exclusion of
      neutrinos from the Fermi bubbles will discriminate between hadronic and leptonic
      models, thus bringing unique information on the still mysterious origin of these
      objects and on the time scale of their formation.

PMID- 23003585
TI  - Electroweak beautygenesis: from b->s CP violation to the cosmic baryon asymmetry.
AB  - We address the possibility that CP violation in B(s)-B(s) mixing may help explain
      the origin of the cosmic baryon asymmetry. We propose a new baryogenesis
      mechanism--"electroweak beautygenesis"--explicitly showing that these two CP
      violating phenomena can be sourced by a common CP phase. As an illustration, we
      work in the two-Higgs-doublet model. Because the relevant CP phase is flavor off
      diagonal, this mechanism is less severely constrained by null results of electric
      dipole moment searches than other scenarios. We show how measurements of flavor
      observables by the D0, CDF, and LHCb collaborations test this scenario.

PMID- 23003586
TI  - Vector boson mass generation without new fields.
AB  - Previously a model of only vector fields with a local U(1)?SU(2) symmetry was
      introduced for which one finds a massless U(1) photon and a massive SU(2) vector
      boson in the lattice regularization. Here it is shown that quantization of its
      classical continuum action leads to perturbative renormalization difficulties.
      But, nonperturbative Monte Carlo calculations favor the existence of a quantum
      continuum limit.

PMID- 23003587
TI  - Strangeness contribution to the proton spin from lattice QCD.
AB  - We compute the strangeness and light-quark contributions Deltas, Deltau, and
      Deltad to the proton spin in n(f)=2 lattice QCD at a pion mass of about 285 MeV
      and at a lattice spacing a~0.073 fm, using the nonperturbatively improved
      Sheikholeslami-Wohlert Wilson action. We carry out the renormalization of these
      matrix elements, which involves mixing between contributions from different quark
      flavors. Our main result is the small negative value Deltas(MS)(?(7.4) GeV)=
      0.020(10)(4) of the strangeness contribution to the nucleon spin. The second
      error is an estimate of the uncertainty, due to the missing extrapolation to the
      physical point.

PMID- 23003589
TI  - Complete O(alphas4) QCD corrections to hadronic Z decays.
AB  - Corrections of order alpha(s)(4) for the axial singlet contributions for the
      decay rate of the Z boson into hadrons are evaluated in the limit of the heavy
      top quark mass. Combined with recently finished O(alpha(s)(4)) calculations of
      the nonsinglet corrections, the new results directly lead us to the first
      complete O(alpha(s)(4)) prediction for the total hadronic decay rate of the Z
      boson. The new O(alpha(s)(4)) term in Z-decay rate leads to a significant
      stabilization of the perturbative series, to a reduction of the theory
      uncertainty in the strong coupling constant alpha(s), as extracted from these
      measurements, and to a small shift of the central value.

PMID- 23003240
TI  - Search for production of resonant states in the photon-jet mass distribution
      using pp collisions at ?s=7 TeV collected by the ATLAS detector.
AB  - This Letter describes a model-independent search for the production of new
      resonant states in photon+jet events in 2.11 fb(-1) of proton-proton collisions
      at ?s=7 TeV. We compare the photon+jet mass distribution to a background model
      derived from data and find consistency with the background-only hypothesis. Given
      the lack of evidence for a signal, we set 95% credibility level limits on generic
      Gaussian-shaped signals and on a benchmark excited-quark (q*) model, excluding 2
      TeV Gaussian resonances with cross section times branching fraction times
      acceptance times efficiency near 5 fb and excluding q* masses below 2.46 TeV,
      respectively.

PMID- 23003591
TI  - Ionization suppression of diatomic molecules in an intense midinfrared laser
      field.
AB  - Diatomic molecules (e.g., O(2)) in an intense laser field exhibit a peculiar
      suppressed ionization behavior compared to their companion atoms. Several
      physical models have been proposed to account for this suppression, while no
      consensus has been achieved. In this Letter, we aim to clarify the underlying
      mechanisms behind this molecular ionization suppression. Experimental data
      recorded at midinfrared laser wavelength and its comparison with that at near
      infrared wavelength revealed a peculiar wavelength and intensity dependence of
      the suppressed ionization of O(2) with respect to its companion atom of Xe, while
      N(2) behaves like a structureless atom. It is found that the S-matrix theory
      calculation can reproduce well the experimental observations and unambiguously
      identifies the significant role of two-center interference effect in the
      ionization suppression of O(2).

PMID- 23003590
TI  - Hindered proton collectivity in 16(28)S12: possible magic number at Z=16.
AB  - The reduced transition probability B(E2;0(gs)(+)->2(1)(+)) for (28)S was obtained
      experimentally using Coulomb excitation at 53 MeV/nucleon. The resultant B(E2)
      value 181(31) e(2)fm(4) is smaller than the expectation based on empirical B(E2)
      systematics. The double ratio |M(n)/M(p)|/(N/Z) of the 0(gs)(+)->2(1)(+)
      transition in (28)S was determined to be 1.9(2) by evaluating the M(n) value from
      the known B(E2) value of the mirror nucleus (28)Mg, showing the hindrance of
      proton collectivity relative to that of neutrons. These results indicate the
      emergence of the magic number Z=16 in the |T(z)|=2 nucleus (28)S.

PMID- 23003593
TI  - Fractional quantum Hall physics in Jaynes-Cummings-Hubbard lattices.
AB  - Jaynes-Cummings-Hubbard arrays provide unique opportunities for quantum emulation
      as they exhibit convenient state preparation and measurement, as well as in situ
      tuning of parameters. We show how to realize strongly correlated states of light
      in Jaynes-Cummings-Hubbard arrays under the introduction of an effective magnetic
      field. The effective field is realized by dynamic tuning of the cavity
      resonances. We demonstrate the existence of Laughlin-like fractional quantum Hall
      states by computing topological invariants, phase transitions between
      topologically distinct states, and Laughlin wave function overlap.

PMID- 23003596
TI  - Ubiquity of optical activity in planar metamaterial scatterers.
AB  - Recently it was discovered that periodic lattices of metamaterial scatterers show
      optical activity, even if the scatterers or lattice show no 2D or 3D chirality,
      if the illumination breaks symmetry. We demonstrate that such "pseudochirality"
      is intrinsic to any single planar metamaterial scatterer and in fact has a well
      defined value at a universal bound. We argue that in any circuit model, a nonzero
      electric and magnetic polarizability derived from a single resonance
      automatically imply strong bi-anisotropy, i.e., magnetoelectric cross
      polarizability at the universal bound set by energy conservation. We confirm our
      claim by extracting polarizability tensors and cross sections for handed
      excitation from transmission measurements on near-infrared split ring arrays, and
      electrodynamic simulations for diverse metamaterial scatterers.

PMID- 23003594
TI  - Nonlinear Cherenkov radiation in an anomalous dispersive medium.
AB  - By using ultrathin nonlinear media, the phase velocity of nonlinear polarization
      waves can be continuously adjusted. We realized nonlinear Cherenkov radiation
      (NCR) in an anomalous dispersion medium experimentally, which breaks the minimum
      speed limit of NCR. This modified nonlinear Cherenkov radiation has two new
      special states with respect to its prior, i.e., the degenerate state and extreme
      state. Also, periodically arranged ultrathin nonlinear media can enhance NCR and
      realize the nonlinear Smith-Purcell effect.

PMID- 23003592
TI  - Interference carpets in above-threshold ionization: from the Coulomb-free to the
      Coulomb-dominated regime.
AB  - The velocity map recorded in above-threshold ionization of xenon at 800 nm
      exhibits a distinct carpetlike pattern of maxima and minima for emission in the
      direction approximately perpendicular to the laser polarization. The pattern is
      well reproduced by a numerical solution of the time-dependent Schrodinger
      equation. In terms of the simple-man model and the strong-field approximation, it
      is explained by the constructive and destructive interference of the contribution
      of the long and the short orbit. Strictly perpendicular emission is caused by
      ionization at the two peaks of the laser field per cycle, which results in a
      2homega separation of the above-threshold ionization rings.

PMID- 23003595
TI  - Method for single-shot coherent diffractive imaging of magnetic domains.
AB  - In preparation for real space studies of magnetic domains in a pump-probe setup
      at free-electron laser sources, it is necessary to develop an imaging method
      compatible with the linearly polarized radiation available at these sources. We
      present results from a prototype experiment performed at the synchrotron source
      BESSY II, using a modification of existing phase retrieval techniques. Our
      results show that it is possible to image magnetic domains in real space using
      linear polarized light, and we introduce the concept of a reliability map of our
      reconstructions using Gabor transforms.

PMID- 23003597
TI  - Laser-rate-equation description of optomechanical oscillators.
AB  - We develop a set of laser rate equations that accurately describes mechanical
      amplification in optomechanical oscillators driven by photothermal or radiation
      pressure forces. In the process we introduce a set of parameters describing gain,
      stored energy, slope efficiency, and saturation power of the mechanical laser. We
      identify the three-phonon parametric interactions as a microscopic mechanism
      enabling self-oscillation. Our theory shows remarkable agreement with our
      experimental data, demonstrating that optomechanical self-oscillation is
      essentially a "phonon lasing" process in which an optical pump generates coherent
      acoustic phonons.

PMID- 23003598
TI  - Localized spoof plasmons arise while texturing closed surfaces.
AB  - We demonstrate that textured closed surfaces, i.e., particles made of perfect
      electric conductors (PECs), are able to support localized electromagnetic
      resonances with properties resembling those of localized surface plasmons (LSPs)
      in the optical regime. Because of their similar behavior, we name these types of
      resonances as spoof LSPs. As a way of example, we show the existence of spoof
      LSPs in periodically textured PEC cylinders and the almost perfect analogy to
      optical plasmonics. We also present a metamaterial approach that captures the
      basic ingredients of their electromagnetic response.

PMID- 23003588
TI  - Measurements of the mass and width of the eta(c) using the decay psi(3686)
      >gammaeta(c).
AB  - The mass and width of the lowest-lying S-wave spin singlet charmonium state, the
      eta(c), are measured using a data sample of 1.06*10(8) psi(3686) decays collected
      with the BESIII detector at the BEPCII storage ring. We use a model that
      incorporates full interference between the signal reaction, psi(3686)
      >gammaeta(c), and a nonresonant radiative background to describe the line shape
      of the eta(c) successfully. We measure the eta(c) mass to be 2984.3+/-0.6+/-0.6
      MeV/c(2) and the total width to be 32.0+/-1.2+/-1.0 MeV, where the first errors
      are statistical and the second are systematic.

PMID- 23003599
TI  - Partial nonlinear reciprocity breaking through ultrafast dynamics in a random
      photonic medium.
AB  - We demonstrate that ultrafast nonlinear dynamics gives rise to reciprocity
      breaking in a random photonic medium. Reciprocity breaking is observed via the
      suppression of coherent backscattering, a manifestation of weak localization of
      light. The effect is observed in a pump-probe configuration where the pump
      induces an ultrafast step change of the refractive index during the dwell time of
      the probe light in the material. The dynamical suppression of coherent
      backscattering is reproduced well by a multiple scattering Monte Carlo
      simulation. Ultrafast reciprocity breaking provides a distinct mechanism in
      nonlinear optical media, which opens up avenues for the active manipulation of
      mesoscopic transport, random lasers, and photon localization.

PMID- 23003600
TI  - All-optical control of an individual resonance in a silicon microresonator.
AB  - We experimentally demonstrate selective control of the Q and transmission of an
      individual resonance of an optical microcavity by optically controlling its
      intracavity loss via inverse Raman scattering. A strongly overcoupled resonance
      is brought into critical coupling with continuous tuning of the on-resonance
      transmission by >9 dB and reduction of the intrinsic Q factor by more than a
      factor of five. Adjacent resonances experience minimal disturbance and can be
      selectively controlled by tuning the control beam to the appropriate control
      resonance. These dynamics are analogous to Zeno effects observed in decoherence
      driven atomic ensembles and two-level systems.

PMID- 23003601
TI  - Coalescence preference depends on size inequality.
AB  - During bubble or droplet coalescence, there is a puzzling tendency for the
      coalesced bubble or droplet to be preferentially placed closer to the larger of
      its two parents. We confirm that this preference is a function of parent size
      ratio by directly visualizing coalescing air bubbles on an oil-water interface
      and coalescing water droplets immersed in oil. We find that the final position of
      the coalesced sphere is controlled by surface energy release and is related to
      the parent size ratio by a power-law relationship. 

PMID- 23003244
TI  - Observation of spin correlation in tt- events from pp collisions at ?s=7 TeV
      using the ATLAS detector.
AB  - A measurement of spin correlation in tt[over -] production is reported using data
      collected with the ATLAS detector at the LHC, corresponding to an integrated
      luminosity of 2.1 fb(-1). Candidate events are selected in the dilepton topology
      with large missing transverse energy and at least two jets. The difference in
      azimuthal angle between the two charged leptons in the laboratory frame is used
      to extract the correlation between the top and antitop quark spins. In the
      helicity basis the measured degree of correlation corresponds to
      A(helicity)=0.40(-0.08)(+0.09), in agreement with the next-to-leading-order
      standard model prediction. The hypothesis of zero spin correlation is excluded at
      5.1 standard deviations.

PMID- 23003602
TI  - Turbulence effect on cloud radiation.
AB  - The effect of turbulent clustering of water droplets on radiative transfer is
      investigated by means of both a three-dimensional direct numerical simulation of
      particle-laden homogeneous isotropic turbulence and a radiative transfer
      simulation based on a Monte Carlo photon tracing method. The results show that
      turbulent clustering causes the formation of void regions of droplets and hence
      increases the direct transmittance. This effect decreases as the turbulent
      Reynolds number increases and is estimated to be negligibly small under the
      conditions in real clouds.

PMID- 23003603
TI  - Ultimate regime of high Rayleigh number convection in a porous medium.
AB  - Well-resolved direct numerical simulations of 2D Rayleigh-Benard convection in a
      porous medium are presented for Rayleigh numbers Ra<=4*10(4) which reveal that,
      contrary to previous indications, the linear classical scaling for the Nusselt
      number, Nu~Ra, is attained asymptotically. The flow dynamics are analyzed, and
      the interior of the vigorously convecting system is shown to be increasingly well
      described as Ra->infinity by a simple columnar "heat-exchanger" model with a
      single horizontal wave number k and a linear background temperature field. The
      numerical results are approximately fitted by k~Ra(0.4).

PMID- 23003604
TI  - Multicavity x-ray Fabry-Perot resonance with ultrahigh resolution and contrast.
AB  - Realization of x-ray Fabry-Perot (FP) resonance in back-Bragg-reflection crystal
      cavities has been proposed and explored for many years, but to date no
      satisfactory performance has been achieved. Here we show that single-cavity
      crystal resonators intrinsically have limited finesse and efficiency. To break
      this limit, we demonstrate that monolithic multicavity resonators with equal
      width cavities and specific plate thickness ratios can generate ultrahigh
      resolution FP resonance with high efficiency, steep peak tails, and ultrahigh
      contrast simultaneously. The resonance mechanism is similar to that of
      sequentially cascaded single-cavity resonators. The ultranarrow-bandwidth FP
      resonance is anticipated to have various applications, including modern ultrahigh
      resolution or precision x-ray monochromatization, spectroscopy, coherence
      purification, coherent diffraction, phase contrast imaging, etc.

PMID- 23003605
TI  - Instantaneous normal mode analysis of melting of finite dust clusters.
AB  - The experimental melting transition of finite two-dimensional dust clusters in a
      dusty plasma is analyzed using the method of instantaneous normal modes. In the
      experiment, dust clusters are heated in a thermodynamic equilibrium from a solid
      to a liquid state using a four-axis laser manipulation system. The fluid
      properties of the dust cluster, such as the diffusion constant, are measured from
      the instantaneous normal mode analysis. Thereby, the phase transition of these
      finite clusters is approached from the liquid phase. From the diffusion
      constants, unique melting temperatures have been assigned to dust clusters of
      various sizes that very well reflect their dynamical stability properties.

PMID- 23003607
TI  - Runaway positrons in fusion plasmas.
AB  - Runaway positrons can be produced in the presence of runaway electron avalanches
      in magnetized plasmas. In this Letter, we determine the positron distribution,
      the fraction of runaway positrons, and the parametric dependences of their
      synchrotron radiation spectrum. We show that the maximum production occurs around
      gamma(e)?30, where gamma(e) is the Lorentz factor of the fast electrons. For an
      avalanching positron distribution typical of tokamak plasmas, the maximum of the
      synchrotron radiation spectrum should be around a micron. The radiated power and
      spectrum shape are sensitive to the plasma parameters. Apart from its intrinsic
      interest, detection of radiation from positrons could be a diagnostic tool to
      understand the properties of the medium they propagate through.

PMID- 23003608
TI  - Diffusion in ionic mixtures across coupling regimes.
AB  - Molecular dynamics simulations are used to investigate the diffusion properties
      of one-component plasmas and binary ionic mixtures from the weakly to the
      strongly coupled regimes. A physically motivated model for the diffusivities is
      proposed that reproduces the simulation data and gives insight into the nature of
      ionic motions and interactions in plasmas across the coupling regimes. The model
      extends the widely used Chapman-Spitzer theory from the weakly to the moderately
      coupled regime. In the strongly coupled regime, diffusion is modeled in terms of
      thermally activated jumps between equilibrium positions separated by an energy
      barrier. The basic ideas discussed are applicable to the study of other transport
      coefficients.

PMID- 23003606
TI  - Rayleigh-Taylor instability of an ultrathin foil accelerated by the radiation
      pressure of an intense laser.
AB  - We report experimental evidence for a Rayleigh-Taylor-like instability driven by
      radiation pressure of an ultraintense (10(21) W/cm(2)) laser pulse. The
      instability is witnessed by the highly modulated profile of the accelerated
      proton beam produced when the laser irradiates a 5 nm diamondlike carbon (90% C,
      10% H) target. Clear anticorrelation between bubblelike modulations of the proton
      beam and transmitted laser profile further demonstrate the role of the radiation
      pressure in modulating the foil. Measurements of the modulation wavelength, and
      of the acceleration from Doppler-broadening of back-reflected light, agree
      quantitatively with particle-in-cell simulations performed for our experimental
      parameters and which confirm the existence of this instability.

PMID- 23003609
TI  - First resolved observations of the demagnetized electron-diffusion region of an
      astrophysical magnetic-reconnection site.
AB  - Spatially resolved, diagnostic signatures across the X-line and electron
      diffusion region (EDR) by the Polar spacecraft are reported at Earth's
      magnetopause. The X-line traversal has a local electron's skin depth scale.
      First, resolved EDR profiles are presented with peak electron thermal Mach
      numbers >1.5, anisotropy >7, calibrated electron agyrotropy >1, and misordered
      expansion parameters indicative of demagnetization and strong (150 eV) increases
      in electron temperature. The amplitude and phase of these profiles correlate well
      with a guide geometry kinetic simulation of collisionless magnetic reconnection.
      Such high resolution diagnosis has been made possible by data processing
      techniques that afford an 11-fold reduction in the aliasing time for the electron
      moments.

PMID- 23003610
TI  - Quantum tricriticality and phase transitions in spin-orbit coupled Bose-Einstein
      condensates.
AB  - We consider a spin-orbit coupled configuration of spin-1/2 interacting bosons
      with equal Rashba and Dresselhaus couplings. The phase diagram of the system at
      T=0 is discussed with special emphasis on the role of the interaction treated in
      the mean-field approximation. For a critical value of the density and of the
      Raman coupling we predict the occurrence of a characteristic tricritical point
      separating the spin mixed, the phase separated, and the zero momentum states of
      the Bose gas. The corresponding quantum phases are investigated analyzing the
      momentum distribution, the longitudinal and transverse spin polarization, and the
      emergence of density fringes. The effect of harmonic trapping as well as the role
      of the breaking of spin symmetry in the interaction Hamiltonian are also
      discussed.

PMID- 23003611
TI  - Expansion of 1D polarized superfluids: the Fulde-Ferrell-Larkin-Ovchinnikov state
      reveals itself.
AB  - We study the expansion dynamics of a one-dimensional polarized Fermi gas after
      its sudden release from confinement using both the mean-field Bogoliubov-de
      Gennes and the numerically unbiased time-evolving block decimation methods. Our
      results show that experimentally observable spin density modulations, directly
      related to the presence of a Fulde-Ferrell-Larkin-Ovchinnikov state, develop
      during the expansion of the cloud. Our work therefore provides a robust
      theoretical proposal for the detection of this long-sought state.

PMID- 23003612
TI  - Peierls substitution in an engineered lattice potential.
AB  - Artificial gauge fields open the possibility to realize quantum many-body systems
      with ultracold atoms, by engineering Hamiltonians usually associated with
      electronic systems. In the presence of a periodic potential, artificial gauge
      fields may bring ultracold atoms closer to the quantum Hall regime. Here, we
      describe a one-dimensional lattice derived purely from effective Zeeman shifts
      resulting from a combination of Raman coupling and radio-frequency magnetic
      fields. In this lattice, the tunneling matrix element is generally complex. We
      control both the amplitude and the phase of this tunneling parameter,
      experimentally realizing the Peierls substitution for ultracold neutral atoms.

PMID- 23003613
TI  - Tunable gauge potential for neutral and spinless particles in driven optical
      lattices.
AB  - We present a universal method to create a tunable, artificial vector gauge
      potential for neutral particles trapped in an optical lattice. The necessary
      Peierls phase of the hopping parameters between neighboring lattice sites is
      generated by applying a suitable periodic inertial force such that the method
      does not rely on any internal structure of the particles. We experimentally
      demonstrate the realization of such artificial potentials, which generate ground
      state superfluids at arbitrary nonzero quasimomentum. We furthermore investigate
      possible implementations of this scheme to create tunable magnetic fluxes, going
      towards model systems for strong-field physics.

PMID- 23003614
TI  - Anomalous behavior of solid 4He in porous Vycor glass.
AB  - The low temperature properties of solid (4)He contained in porous Vycor glass
      have been investigated utilizing a two-mode compound torsional oscillator. At low
      temperatures, we find period-shift signals for the solid similar to those
      reported by Kim and Chan [Nature (London) 427, 225 (2004)], which were taken at
      the time as evidence for a supersolid helium phase. The supersolid is expected to
      have properties analogous to those of a conventional superfluid, where the
      superfluid behavior is independent of frequency and the ratio of the superfluid
      signals observed at two different mode periods will depend only on the ratio of
      the sensitivities of the mode periods to mass loading. In the case of helium
      studies in Vycor, one can compare the period-shift signals seen for a
      conventional superfluid film with signals obtained for a supersolid within the
      same Vycor sample. We find, contrary to our own expectations, that the signals
      observed for the solid display a marked period dependence not seen in the case of
      the superfluid film. This surprising result suggests that the low temperature
      response of solid (4)He in Vycor is more complex than previously assumed and
      cannot be thought of as a simple superfluid.

PMID- 23003615
TI  - Direct observation of quantum phonon fluctuations in a one-dimensional Bose gas.
AB  - We report the first direct observation of collective quantum fluctuations in a
      continuous field. Shot-to-shot atom number fluctuations in small subvolumes of a
      weakly interacting, ultracold atomic 1D cloud are studied using in situ
      absorption imaging and statistical analysis of the density profiles. In the cloud
      centers, well in the quantum quasicondensate regime, the ratio of chemical
      potential to thermal energy is MU/k(B)T?4, and, owing to high resolution, up to
      20% of the microscopically observed fluctuations are quantum phonons. Within a
      nonlocal analysis at variable observation length, we observe a clear deviation
      from a classical field prediction, which reveals the emergence of dominant
      quantum fluctuations at short length scales, as the thermodynamic limit breaks
      down.

PMID- 23003616
TI  - Knudsen-to-hydrodynamic crossover in liquid 3He in a high-porosity aerogel.
AB  - We present a combined experimental and theoretical study of the drag force acting
      on a high porosity aerogel immersed in liquid (3)He and its effect on sound
      propagation. The drag force is characterized by the Knudsen number, which is
      defined as the ratio of the quasiparticle mean free path to the radius of an
      aerogel strand. Evidence of the Knudsen-hydrodynamic crossover is clearly
      demonstrated by a drastic change in the temperature dependence of ultrasound
      attenuation in 98% porosity aerogel. Our theoretical analysis shows that the
      frictional sound damping caused by the drag force is governed by distinct laws in
      the two regimes, providing excellent agreement with the experimental observation.

PMID- 23003617
TI  - Laser heating control with polarized light in isolated multiwalled carbon
      nanotubes.
AB  - We propose a novel method of laser heating control only through change in
      polarization of the incident light, keeping its power density constant. The idea
      combines an antenna effect found in isolated multiwalled carbon nanotubes and the
      possibility of their heating by light illumination. To observe this we used the
      Raman spectroscopy technique, where the heating manifests itself in a pronounced
      downshift of the Raman G and 2D lines as a function of the polarization angle.
      Our method can be useful in field electron emission devices or in selective
      nanotubes heating and destruction. It can also be extended to other one
      dimensional nano-objects, if only certain conditions are fulfilled.

PMID- 23003618
TI  - Damage-cluster distributions and size effect on strength in compressive failure.
AB  - We investigate compressive failure of heterogeneous materials on the basis of a
      continuous progressive-damage model. The model explicitly accounts for tensile
      and shear local damage and reproduces the main features of compressive failure of
      brittle materials like rocks or ice. We show that the size distribution of damage
      clusters, as well as the evolution of an order parameter--the size of the largest
      damage cluster--argue for a critical interpretation of fracture. The compressive
      failure strength follows a normal distribution with a very small size effect on
      the mean strength, in good agreement with experiments.

PMID- 23003619
TI  - Apparent inverse Gibbs-Thomson effect in dealloyed nanoporous nanoparticles.
AB  - The Gibbs-Thomson effect (the reduction of local chemical potential due to
      nanoscale curvature) predicts that nanoparticles of radius r dissolve at lower
      electrochemical potentials than bulk materials, decreasing as 1/r. However, we
      show here that if the particle is an alloy--susceptible to selective dissolution
      (dealloying) and nanoporosity evolution--then complete selective electrochemical
      dissolution and porosity evolution require a higher electrochemical potential
      than the comparable bulk planar material, increasing empirically as 1/r. This is
      a kinetic effect, which we demonstrate via kinetic Monte Carlo simulation. Our
      model shows that in the initial stages of dissolution, the less noble particle
      component is easily stripped from the nanoparticle surface, but owing to an
      increased mobility of the more noble atoms, the surface of the particle quickly
      passivates. At a fixed electrochemical potential, porosity and complete
      dealloying can only evolve if fluctuations in the surface passivation layer are
      sufficiently long-lived to allow dissolution from percolating networks of the
      less-noble component that penetrate through the bulk of the particle.

PMID- 23003620
TI  - Electronic stopping power in gold: the role of d electrons and the H/He anomaly.
AB  - The electronic stopping power of H and He moving through gold is obtained to high
      accuracy using time-evolving density-functional theory, thereby bringing usual
      first principles accuracies into this kind of strongly coupled, continuum
      nonadiabatic processes in condensed matter. The two key unexplained features of
      what observed experimentally have been reproduced and understood: (i) The
      nonlinear behavior of stopping power versus velocity is a gradual crossover as
      excitations tail into the d-electron spectrum; and (ii) the low-velocity H/He
      anomaly (the relative stopping powers are contrary to established theory) is
      explained by the substantial involvement of the d electrons in the screening of
      the projectile even at the lowest velocities where the energy loss is generated
      by s-like electron-hole pair formation only.

PMID- 23003621
TI  - Structural and electronic properties of T graphene: a two-dimensional carbon
      allotrope with tetrarings.
AB  - T graphene, a two-dimensional carbon allotrope with tetrarings, is investigated
      by first-principles calculations. We demonstrate that buckled T graphene has
      Dirac-like fermions and a high Fermi velocity similar to graphene even though it
      has nonequivalent bonds and possesses no hexagonal honeycomb structure. New
      features of the linear dispersions that are different from graphene are revealed.
      pi and pi* bands and the two comprising sublattices are the key factors for the
      emergence of Dirac-like fermions. T graphene and its two types of nanoribbon are
      expected to possess additional properties over graphene due to its different band
      structure.

PMID- 23003622
TI  - Growing point-to-set length scale correlates with growing relaxation times in
      model supercooled liquids.
AB  - It has been demonstrated recently that supercooled liquids sharing simple
      structural features (e.g. pair distribution functions) may exhibit strikingly
      distinct dynamical behavior. Here we show that a more subtle structural feature
      correlates with relaxation times in three simulated systems that have nearly
      identical radial distribution functions but starkly different dynamical behavior.
      In particular, for the first time we determine the thermodynamic "point-to-set"
      length scale in several canonical model systems and demonstrate the quantitative
      connection between this length scale and the growth of relaxation times. Our
      results provide clues necessary for distinguishing competing theories of the
      glass transition.

PMID- 23003623
TI  - Systematic improvement of classical nucleation theory.
AB  - We reconsider the applicability of classical nucleation theory (CNT) to the
      calculation of the free energy of solid cluster formation in a liquid and its use
      to the evaluation of interface free energies from nucleation barriers. Using two
      different freezing transitions (hard spheres and NaCl) as test cases, we first
      observe that the interface-free-energy estimates based on CNT are generally in
      error. As successive refinements of nucleation-barrier theory, we consider
      corrections due to a nonsharp solid-liquid interface and to a nonspherical
      cluster shape. Extensive calculations for the Ising model show that corrections
      due to a nonsharp and thermally fluctuating interface account for the barrier
      shape with excellent accuracy. The experimental solid nucleation rates that are
      measured in colloids are better accounted for by these non-CNT terms, whose
      effect appears to be crucial in the interpretation of data and in the extraction
      of the interface tension from them.

PMID- 23003624
TI  - Relaxation time of high-density amorphous ice.
AB  - Amorphous water plays a fundamental role in astrophysics, cryoelectron
      microscopy, hydration of matter, and our understanding of anomalous liquid water
      properties. Yet, the characteristics of the relaxation processes taking place in
      high-density amorphous ice (HDA) are unknown. We here reveal that the relaxation
      processes in HDA at 110-135 K at 0.1-0.2 GPa are of collective and global nature,
      resembling the alpha relaxation in glassy material. Measured relaxation times
      suggest liquid-like relaxation characteristics in the vicinity of the
      crystallization temperature at 145 K. By carefully relaxing pressurized HDA for
      several hours at 135 K, we produce a state that is closer to the ideal glass
      state than all HDA states discussed so far in literature.

PMID- 23003625
TI  - Tension and stiffness of the hard sphere crystal-fluid interface.
AB  - A combination of fundamental measure density functional theory and Monte Carlo
      computer simulation is used to determine the orientation-resolved interfacial
      tension and stiffness for the equilibrium hard-sphere crystal-fluid interface.
      Microscopic density functional theory is in quantitative agreement with
      simulations and predicts a tension of 0.66k(B)T/sigma(2) with a small anisotropy
      of about 0.025k(B)T and stiffnesses with, e.g., 0.53k(B)T/sigma(2) for the (001)
      orientation and 1.03k(B)T/sigma(2) for the (111) orientation. Here k(B)T is
      denoting the thermal energy and sigma the hard-sphere diameter. We compare our
      results with existing experimental findings.

PMID- 23003626
TI  - Patterning of heteroepitaxial overlayers from nano to micron scales.
AB  - Thin heteroepitaxial overlayers have been proposed as templates to generate
      stable, self-organized nanostructures at large length scales, with a variety of
      important technological applications. However, modeling strain-driven self
      organization is a formidable challenge due to different length scales involved.
      In this Letter, we present a method for predicting the patterning of ultrathin
      films on micron length scales with atomic resolution. We make quantitative
      predictions for the type of superstructures (stripes, honeycomb, triangular) and
      length scale of pattern formation of two metal-metal systems, Cu on Ru(0001) and
      Cu on Pd(111). Our findings are in excellent agreement with previous experiments
      and call for future experimental investigations of such systems.

PMID- 23003627
TI  - Asymmetric transport efficiencies of positive and negative ion defects in
      amorphous ice.
AB  - Hydronium (H(3)O(+)) ions at an ice surface penetrate into its interior over a
      substantially longer distance than hydroxide (OH(-)) ions. The observation was
      made by conducting reactive ion scattering and infrared spectroscopic
      measurements for the acid-base reaction between surface H(3)O(+) (or OH(-)) and
      NH(3) (or NH(4)(+)) trapped inside an amorphous ice film at low temperature (<100
      K). The study reveals very different transport efficiencies of positive and
      negative ion defects in ice. This difference is explained by the occurrence of an
      efficient proton-relay channel for H(3)O(+), which does not exist for OH(-).

PMID- 23003628
TI  - How things get stuck: kinetics, elastohydrodynamics, and soft adhesion.
AB  - We consider the sticking of a fluid-immersed colloidal particle with a substrate
      coated by polymeric tethers, a model for soft, wet adhesion in many natural and
      artificial systems. Our theory accounts for the kinetics of binding, the
      elasticity of the tethers, and the hydrodynamics of fluid drainage between the
      colloid and the substrate, characterized by three dimensionless parameters: the
      ratio of the viscous drainage time to the kinetics of binding, the ratio of
      elastic to thermal energies, and the size of the particle relative to the height
      of the polymer brush. For typical experimental parameters and discrete families
      of tethers, we find that adhesion proceeds via punctuated steps, where rapid
      transitions to increasingly bound states are separated by slow aging transients,
      consistent with recent observations. Our results also suggest that the bound
      particle is susceptible to fluctuation-driven instabilities parallel to the
      substrate.

PMID- 23003629
TI  - Atomically abrupt liquid-oxide interface stabilized by self-regulated interfacial
      defects: the case of Al/Al2O3 interfaces.
AB  - The atomic and electronic structures of the liquid Al/(0001) alpha-Al(2)O(3)
      interfaces are investigated by first-principles molecular dynamics simulations.
      Surprisingly, the formed liquid-solid interface is always atomically abrupt and
      is characterized by a transitional Al layer that contains a fixed concentration
      of Al vacancies (~10 at.%). We find that the self-regulation of the defect
      density in the metal layer is due to the fact that the formation energy of the Al
      vacancies is readjusted in a way that opposes changes in the defect density. The
      negative-feedback effect stabilizes the defected transitional layer and maintains
      the atomic abruptness at the interface. The proposed mechanism is generally
      applicable to other liquid-metal/metal-oxide systems, and thus of significant
      importance in understanding the interface structures at high temperature.

PMID- 23003630
TI  - Accessing surface Brillouin zone and band structure of picene single crystals.
AB  - We have experimentally revealed the band structure and the surface Brillouin zone
      of insulating picene single crystals (SCs), the mother organic system for a
      recently discovered aromatic superconductor, with ultraviolet photoelectron
      spectroscopy (UPS) and low-energy electron diffraction with a laser for
      photoconduction. A hole effective mass of 2.24m(0) and the hole mobility
      MU(h)>=9.0 cm(2)/V s (298 K) were deduced in the Gamma-Y direction. We have
      further shown that some picene SCs did not show charging during UPS even without
      the laser, which indicates that pristine UPS works for high-quality organic SCs.

PMID- 23003631
TI  - Room temperature coherent spin alignment of silicon vacancies in 4H- and 6H-SiC.
AB  - We report the realization of the optically induced inverse population of the
      ground-state spin sublevels of the silicon vacancies (V(Si)) in silicon carbide
      (SiC) at room temperature. The data show that the probed silicon vacancy spin
      ensemble can be prepared in a coherent superposition of the spin states. Rabi
      nutations persist for more than 80 MUs. Two opposite schemes of the optical
      alignment of the populations between the ground-state spin sublevels of the
      silicon vacancy upon illumination with unpolarized light are realized in 4H- and
      6H-SiC at room temperature. These altogether make the silicon vacancy in SiC a
      very favorable defect for spintronics, quantum information processing, and
      magnetometry.

PMID- 23003632
TI  - How to find out the density of states in disordered organic semiconductors.
AB  - We suggest a recipe on how to determine the density of states (DOS) in disordered
      organic semiconductors from the measured dependence of the charge carrier
      mobility on the concentration of carriers n. The recipe is based on a theory for
      the concentration-dependent mobility. As an example, we apply our theoretical
      results to experimental data obtained on two polymers and show that from the
      class of trial DOS functions g(epsilon)?exp{-(epsilon/sigma)(p)}, only those with
      p>1.8 can explain the experimental results. In particular, we claim that the
      concentration-independent mobility at low n evidences that the DOS cannot be
      purely exponential, which is in contrast to numerous recent assumptions in the
      literature.

PMID- 23003633
TI  - Theoretical design of a shallow donor in diamond by lithium-nitrogen codoping.
AB  - We propose a new substitutional impurity complex in diamond composed of a lithium
      atom that is tetrahedrally coordinated by four nitrogen atoms (LiN(4)). Density
      functional calculations are consistent with the hydrogenic impurity model, both
      supporting the prediction that this complex is a shallow donor with an activation
      energy of 0.27+/-0.06 eV. Three paths to the experimental realization of the
      LiN(4) complex in diamond are proposed and theoretically analyzed.

PMID- 23003634
TI  - Subterahertz acoustical pumping of electronic charge in a resonant tunneling
      device.
AB  - We demonstrate that controlled subnanosecond bursts of electronic charge can be
      transferred through a resonant tunneling diode by successive picosecond acoustic
      pulses. The effect exploits the nonlinear current-voltage characteristics of the
      device and its asymmetric response to the compressive and tensile components of
      the strain pulse. This acoustoelectronic pump opens new possibilities for the
      control of quantum phenomena in nanostructures.

PMID- 23003635
TI  - Evidence for spin-flip scattering and local moments in dilute fluorinated
      graphene.
AB  - The issue of whether local magnetic moments can be formed by introducing adatoms
      into graphene is of intense research interest because it opens the window to
      fundamental studies of magnetism in graphene, as well as of its potential
      spintronics applications. To investigate this question, we measure, by exploiting
      the well-established weak localization physics, the phase coherence length L(Phi)
      in dilute fluorinated graphene. L(Phi) reveals an unusual saturation below ~10 K,
      which cannot be explained by nonmagnetic origins. The corresponding phase
      breaking rate increases with decreasing carrier density and increases with
      increasing fluorine density. These results provide strong evidence for spin-flip
      scattering and point to the existence of an adatom-induced local magnetic moment
      in fluorinated graphene. Our results will stimulate further investigations of
      magnetism and spintronics applications in adatom-engineered graphene.

PMID- 23003636
TI  - Upstream neutral modes in the fractional quantum Hall effect regime: heat waves
      or coherent dipoles.
AB  - Counterpropagating (upstream) chiral neutral edge modes, which were predicted to
      be present in hole-conjugate states, were observed recently in a variety of
      fractional quantum Hall states (nu=2/3, nu=3/5, nu=8/3, and nu=5/2), by measuring
      the charge noise that resulted after partitioning the neutral mode by a
      constriction (denoted, as N->C). Particularly noticeable was the observation of
      such modes in the nu=5/2 fractional state--as it sheds light on the non-Abelian
      nature of the state's wave function. Yet, the nature of these unique, upstream,
      chargeless modes and the microscopic process in which they generate shot noise,
      are not understood. Here, we study the ubiquitous nu=2/3 state and report of two
      main observations: First, the nature of the neutral modes was tested by
      "colliding" two modes, emanating from two opposing sources, in a narrow
      constriction. The resultant charge noise was consistent with local heating of the
      partitioned quasiparticles. Second, partitioning of a downstream charge mode by a
      constriction gave birth to a dual process, namely, the appearance of an upstream
      neutral mode (C->N). In other words, splitting "hole conjugated" type
      quasiparticles will lead to an energy loss and decoherence, with energy carried
      away by neutral modes.

PMID- 23003637
TI  - Quantum interference between three two-spin states in a double quantum dot.
AB  - Qubits based on the singlet (S) and the triplet (T(0), T(+)) states in double
      quantum dots have been demonstrated in separate experiments. It has been recently
      proposed theoretically that under certain conditions a quantum interference could
      occur from the interplay between these two qubit species. Here we report
      experiments and modeling that confirm these theoretical predictions and identify
      the conditions under which this interference occurs. Density matrix calculations
      show that the interference pattern manifests primarily via the occupation of the
      common singlet state. The S/T(0) qubit is found to have a much longer coherence
      time as compared to the S/T(+) qubit.

PMID- 23003638
TI  - Tailoring light-matter interaction with a nanoscale plasmon resonator.
AB  - We propose and demonstrate a new approach for achieving enhanced light-matter
      interactions with quantum emitters. Our approach makes use of a plasmon resonator
      composed of defect-free, highly crystalline silver nanowires surrounded by
      patterned dielectric distributed Bragg reflectors. These resonators have an
      effective mode volume (V(eff)) 2 orders of magnitude below the diffraction limit
      and a quality factor (Q) approaching 100, enabling enhancement of spontaneous
      emission rates by a factor exceeding 75 at the cavity resonance. We also show
      that these resonators can be used to convert a broadband quantum emitter to a
      narrow-band single-photon source with color-selective emission enhancement.

PMID- 23003639
TI  - Nonlocal transport near charge neutrality point in a two-dimensional electron
      hole system.
AB  - Nonlocal resistance is studied in a two-dimensional system with a simultaneous
      presence of electrons and holes in a 20 nm HgTe quantum well. A large nonlocal
      electric response is found near the charge neutrality point in the presence of a
      perpendicular magnetic field. We attribute the observed nonlocality to the edge
      state transport via counterpropagating chiral modes similar to the quantum spin
      Hall effect at a zero magnetic field and graphene near a Landau filling factor
      nu=0.

PMID- 23003640
TI  - Optoelectronic properties in monolayers of hybridized graphene and hexagonal
      boron nitride.
AB  - We explain the nature of the electronic energy gap and optical absorption
      spectrum of carbon-boron-nitride (CBN) monolayers using density functional
      theory, GW and Bethe-Salpeter calculations. The band structure and the optical
      absorption are regulated by the C domain size rather than the composition (as
      customary for bulk semiconductor alloys). The C and BN quasiparticle states lie
      at separate energy for C and BN, with little mixing for energies near the band
      edge where states are chiefly C in character. The resulting optical absorption
      spectra show two distinct peaks whose energy and relative intensity vary with
      composition in agreement with the experiment. The monolayers present strongly
      bound excitons localized within the C domains, with binding energies of the order
      of 0.5-1.5 eV dependent on the C domain size. The optoelectronic properties
      result from the overall monolayer band structure, and cannot be understood as a
      superposition of the properties of bulklike C and BN domains.

PMID- 23003641
TI  - Understanding the Josephson current through a Kondo-correlated quantum dot.
AB  - We study the Josephson current 0-pi transition of a quantum dot tuned to the
      Kondo regime. The physics can be quantitatively captured by the numerically exact
      continuous time quantum Monte Carlo method applied to the single-impurity
      Anderson model with Bardeen-Cooper-Schrieffer superconducting leads. For a
      comparison to an experiment, the tunnel couplings are determined by fitting the
      normal-state linear conductance. Excellent agreement for the dependence of the
      critical Josephson current on the level energy is achieved. For increased tunnel
      couplings the Kondo scale becomes comparable to the superconducting gap, and the
      regime of the strongest competition between superconductivity and Kondo
      correlations is reached; we predict the gate voltage dependence of the critical
      current in this regime.

PMID- 23003642
TI  - Evidence of a spin resonance mode in the iron-based superconductor
      Ba(0.6)K(0.4)Fe2As2 from scanning tunneling spectroscopy.
AB  - We used high-resolution scanning tunneling spectroscopy to study the hole-doped
      iron pnictide superconductor Ba(0.6)K(0.4)Fe(2)As(2) (T(c)=38 K). Features of a
      bosonic excitation (mode) are observed in the measured quasiparticle density of
      states. The bosonic features are intimately associated with the superconducting
      order parameter and have a mode energy of ~14 meV, similar to the spin resonance
      measured by inelastic neutron scattering. These results indicate a strong
      electron-spin excitation coupling in iron pnictide superconductors, similar to
      that in high-T(c) copper oxide superconductors.

PMID- 23003643
TI  - Feedback effect on high-energy magnetic fluctuations in the model high
      temperature superconductor HgBa2CuO(4+delta) observed by electronic Raman
      scattering.
AB  - We use electronic Raman scattering to study the model single-layer cuprate
      superconductor HgBa(2)CuO(4+delta). In an overdoped sample, we observe a
      pronounced amplitude enhancement of a high-energy peak related to two-magnon
      excitations in insulating cuprates upon cooling below the critical temperature
      T(c). This effect is accompanied by the appearance of the superconducting gap and
      a pairing peak above the gap in the Raman spectrum, and it can be understood as a
      hitherto-undetected feedback effect on the high-energy magnetic fluctuations due
      to the Cooper pairing interaction. This implies a direct involvement of the high
      energy magnetic fluctuations in the pairing mechanism. All of these effects occur
      already above T(c) in two underdoped samples, demonstrating a related feedback
      mechanism associated with the pseudogap.

PMID- 23003644
TI  - Boundary-locality and perturbative structure of entanglement spectra in gapped
      systems.
AB  - The entanglement between two parts of a many-body system can be characterized in
      detail by the entanglement spectrum. Focusing on gapped phases of several one
      dimensional systems, we show how this spectrum is dominated by contributions from
      the boundary between the parts. This contradicts the view of an "entanglement
      Hamiltonian" as a bulk entity. The boundary-local nature of the entanglement
      spectrum is clarified through its hierarchical level structure, through the
      combination of two single-boundary spectra to form a two-boundary spectrum, and
      finally through consideration of dominant eigenfunctions of the entanglement
      Hamiltonian. We show consequences of boundary-locality for perturbative
      calculations of the entanglement spectrum.

PMID- 23003645
TI  - Enhanced transmission through squeezed modes in a self-cladding magnonic
      waveguide.
AB  - We study spin-wave propagation in 360-nm wide Ni(80)Fe(20) nanowires using all
      electrical spin-wave spectroscopy. Creating a zigzag-like magnetization state, we
      find enhanced spin-wave transmission compared to the states of more homogeneous
      magnetization. Micromagnetic simulations show that the spin waves propagate in
      narrow channels, which in particular, are remotely positioned from the edges. The
      internal channels reflect field-controlled self-cladding. Interestingly, rotation
      of the magnetic field at a specific value is found to vary the propagation
      velocity without changing the eigenfrequency. This opens the perspective of the
      velocity modulation transistor following a concept known from semiconductor
      electronics.

PMID- 23003646
TI  - Symmetry of orbital order in Fe3O4 studied by Fe L(2,3) resonant x-ray
      diffraction.
AB  - We studied the symmetry of the Fe 3d wave function in magnetite below the Verwey
      temperature T(V) with resonant soft-x-ray diffraction. Although the lattice
      structure of the low-temperature phase of Fe(3)O(4) is well described by the
      pseudo-orthorhombic Pmca with a slight monoclinic P2/c distortion, we find that
      the 3d wave function does not reflect the Pmca symmetry, and its distortion
      toward monoclinic symmetry is by far larger than that of the lattice. The result
      supports a scenario in which the Verwey transition involves the ordering of t(2g)
      orbitals with complex-number coefficients.

PMID- 23003647
TI  - Itinerant half-metal spin-density-wave state on the hexagonal lattice.
AB  - We consider electrons on a honeycomb or triangular lattice doped to the saddle
      point of the band structure. We assume the system parameters are such that spin
      density wave (SDW) order emerges below a temperature T(N) and investigate the
      nature of the SDW phase. We argue that at T<=T(N), the system develops a uniaxial
      SDW phase whose ordering pattern breaks O(3)*Z(4) symmetry and corresponds to an
      eight-site unit cell with nonuniform spin moments on different sites. This state
      is a half-metal--it preserves the full original Fermi surface, but has gapless
      charged excitations in one spin branch only. It allows for electrical control of
      spin currents and is desirable for nanoscience.

PMID- 23003648
TI  - Space dependent Fermi velocity in strained graphene.
AB  - We investigate some apparent discrepancies between two different models for
      curved graphene: the one based on tight-binding and elasticity theory, and the
      covariant approach based on quantum field theory in curved space. We demonstrate
      that strained or corrugated samples will have a space-dependent Fermi velocity in
      either approach that can affect the interpretation of local probe experiments in
      graphene. We also generalize the tight-binding approach to general inhomogeneous
      strain and find a gauge field proportional to the derivative of the strain tensor
      that has the same form as the one obtained in the covariant approach.

PMID- 23003649
TI  - Finite-temperature dynamical density matrix renormalization group and the Drude
      weight of spin-1/2 chains.
AB  - We propose an easily implemented approach to study time-dependent correlation
      functions of one-dimensional systems at finite-temperature T using the density
      matrix renormalization group. The entanglement growth inherent to any time
      dependent calculation is significantly reduced if the auxiliary degrees of
      freedom which purify the statistical operator are time evolved with the physical
      Hamiltonian but reversed time. We exploit this to investigate the long-time
      behavior of current correlation functions of the XXZ spin-1/2 Heisenberg chain.
      This allows a direct extraction of the Drude weight D at intermediate to large T.
      We find that D is nonzero--and thus transport is dissipationless--everywhere in
      the gapless phase. At low temperatures we establish an upper bound to D by
      comparing with bosonization.

PMID- 23003650
TI  - Possible Fermi liquid in the lightly doped Kitaev spin liquid.
AB  - We study the lightly doped Kitaev spin liquid (LDKSL) and find it to be the Fermi
      liquid. The LDKSL satisfies the two key properties of the standard Landau Fermi
      liquid: the low-energy quasiparticles are well defined and the Fermi sea has the
      quantized volume determined by Luttinger's theorem. These features can be
      observed in angle-resolved photoemission spectroscopy measurements. Meanwhile,
      the LDKSL has the topological Kitaev spin liquid surrounding the Fermi sea. So
      the LDKSL violates the Wiedemann-Franz law and has a large Wilson ratio. These
      results have the potential experimental verifiability in iridates upon doping.

PMID- 23003651
TI  - Domain wall dynamics under nonlocal spin-transfer torque.
AB  - We study spin-diffusion effects within a continuously variable magnetization
      distribution, integrating with micromagnetics the diffusive model of Zhang and Li
      [Phys. Rev. Lett. 93, 127204 (2004)]. Current-driven wall motion is, in the
      steady velocity regime, shown to be adequately described by an effective nonlocal
      nonadiabatic parameter. This parameter is found to be 20% larger than its local
      counterpart for a vortex wall in a NiFe nanostrip and hardly modified for a
      transverse wall. This may account for the yet unexplained experimental evidence
      that vortex walls move more easily under current when compared with transverse
      walls. It is shown that this effective parameter can be derived from the domain
      wall structure at rest.

PMID- 23003652
TI  - Multiple exciton generation by a single photon in single-walled carbon nanotubes.
AB  - Multiple-exciton generation in single-walled carbon nanotubes is investigated
      theoretically. We show that multiple excitons can be directly generated by a
      single photon through resonant coupling with multiexciton states. Further, the
      theoretically predicted threshold energy for this process is consistent with
      recent experimental results. Our calculations clarify the elementary processes of
      multiple-exciton generation in single-walled carbon nanotubes.

PMID- 23003653
TI  - Low-photon-number optical switching with a single quantum dot coupled to a
      photonic crystal cavity.
AB  - We demonstrate fast nonlinear optical switching between two laser pulses with as
      few as 140 photons of pulse energy by utilizing strong coupling between a single
      quantum dot (QD) and a photonic crystal cavity. The cavity-QD coupling is
      modified by a detuned pump pulse, resulting in a modulation of the scattered and
      transmitted amplitude of a time synchronized probe pulse that is resonant with
      the QD. The temporal switching response is measured to be as fast as 120 ps,
      demonstrating the ability to perform optical switching on picosecond timescales.

PMID- 23003654
TI  - Dielectric constant of ionic solutions: a field-theory approach.
AB  - We study the variation of the dielectric response of a dielectric liquid (e.g.
      water) when a salt is added to the solution. Employing field-theoretical methods,
      we expand the Gibbs free energy to first order in a loop expansion and calculate
      self-consistently the dielectric constant. We predict analytically the dielectric
      decrement which depends on the ionic strength in a complex way. Furthermore, a
      qualitative description of the hydration shell is found and is characterized by a
      single length scale. Our prediction fits rather well a large range of
      concentrations for different salts using only one fit parameter related to the
      size of ions and dipoles.

PMID- 23003655
TI  - Fluctuation-preserving coarse graining for biochemical systems.
AB  - Finite stochastic Markov models play a major role in modeling biological systems.
      Such models are a coarse-grained description of the underlying microscopic
      dynamics and can be considered mesoscopic. The level of coarse-graining is to a
      certain extent arbitrary since it depends on the resolution of accommodating
      measurements. Here we present a systematic way to simplify such stochastic
      descriptions which preserves both the meso-micro and the meso-macro connections.
      The former is achieved by demanding locality, the latter by considering cycles on
      the network of states. Our method preserves fluctuations of observables much
      better than naive approaches.

PMID- 23003656
TI  - Optimal heterogeneity for coding in spiking neural networks.
AB  - The effect of cellular heterogeneity on the coding properties of neural
      populations is studied analytically and numerically. We find that heterogeneity
      decreases the threshold for synchronization, and its strength is nonlinearly
      related to the network mean firing rate. In addition, conditions are shown under
      which heterogeneity optimizes network information transmission for either
      temporal or rate coding, with high input frequencies leading to different effects
      for each coding strategy. The results are shown to be robust for more realistic
      conditions.

PMID- 23003657
TI  - Transition path from two apposed membranes to a stalk obtained by a combination
      of particle simulations and string method.
AB  - The formation of an hourglass-shaped passage (stalk) connecting two apposed
      membranes is an essential initial step in membrane fusion. The most probable
      transition path from two separate membranes to a stalk, i.e., the minimum free
      energy path (MFEP), is constructed using a combination of particle simulations
      and string method. For the reversible transition path in the coarse-grained
      membrane model, a collective order parameter, m, can be identified as the local
      difference of hydrophilic and hydrophobic densities. In particle simulations, the
      free energy F[m] as a functional of m is not readily available. This difficulty
      is overcome by an equation-free approach, where the morphology and the excess
      free energy along the MFEP are obtained by an on-the-fly string method. The
      transition state is confirmed by diagonalization of order-parameter fluctuations
      and by the probability of reaching either stalk or bilayer morphology from
      different positions along the MFEP.

PMID- 23003658
TI  - Emergence of spiral wave activity in a mechanically heterogeneous reaction
      diffusion-mechanics system.
AB  - We perform a numerical study of emergent spiral wave activity in a two
      dimensional reaction-diffusion-mechanics medium with a regional inhomogeneity in
      active and passive mechanical properties. We find that self-sustaining spiral
      wave activity emerges for a wide range of mechanical parameters of the
      inhomogeneity via five mechanisms. We classify these mechanisms, relate them to
      parameters of the inhomogeneity, and discuss how these results can be applied to
      understand the onset of cardiac arrhythmias due to regional mechanical
      heterogeneity.

PMID- 23003659
TI  - Mobility of a semiflexible chain confined in a nanochannel.
AB  - The classic results of de Gennes and Odijk describe the mobility of a
      semiflexible chain confined in a nanochannel only in the limits of very weak and
      very strong confinement, respectively. Using Monte Carlo sampling of the Kirkwood
      diffusivity with full hydrodynamic interactions, we show that the mobility of a
      semiflexible chain exhibits a broad plateau as a function of extension before
      transitioning to an Odijk regime, and that the width of the plateau depends on
      the anisotropy of the monomers. For the particular case of DNA in a high ionic
      strength buffer, which has highly anisotropic monomers, we predict that this
      Rouse-like behavior will be observed over most of the measurable chain extensions
      seen in experiments.

PMID- 23003660
TI  - Generalized hydrodynamic treatment of the interplay between restricted transport
      and catalytic reactions in nanoporous materials.
AB  - Behavior of catalytic reactions in narrow pores is controlled by a delicate
      interplay between fluctuations in adsorption-desorption at pore openings,
      restricted diffusion, and reaction. This behavior is captured by a generalized
      hydrodynamic formulation of appropriate reaction-diffusion equations (RDE). These
      RDE incorporate an unconventional description of chemical diffusion in mixed
      component quasi-single-file systems based on a refined picture of tracer
      diffusion for finite-length pores. The RDE elucidate the nonexponential decay of
      the steady-state reactant concentration into the pore and the non-mean-field
      scaling of the reactant penetration depth.

PMID- 23003661
TI  - Orientational order and alignment of elongated particles induced by shear.
AB  - Shear induced alignment of elongated particles is studied experimentally and
      numerically. We show that shear alignment of ensembles of macroscopic particles
      is comparable even on a quantitative level to simple molecular systems, despite
      the completely different types of particle interactions. We demonstrate that for
      dry elongated grains the preferred orientation forms a small angle with the
      streamlines, independent of shear rate across three decades. For a given particle
      shape, this angle decreases with increasing aspect ratio of the particles. The
      shear-induced alignment results in a considerable reduction of the effective
      friction of the granular material.

PMID- 23003662
TI  - Influence of particle shape on bending rigidity of colloidal monolayer membranes
      and particle deposition during droplet evaporation in confined geometries.
AB  - We investigate the influence of particle shape on the bending rigidity of
      colloidal monolayer membranes (CMMs) and on evaporative processes associated with
      these membranes. Aqueous suspensions of colloidal particles are confined between
      glass plates and allowed to evaporate. Confinement creates ribbonlike air-water
      interfaces and facilitates measurement and characterization of CMM geometry
      during drying. Interestingly, interfacial buckling events occur during
      evaporation. Extension of the description of buckled elastic membranes to our
      quasi-2D geometry enables the determination of the ratio of CMM bending rigidity
      to its Young's modulus. Bending rigidity increases with increasing particle
      anisotropy, and particle deposition during evaporation is strongly affected by
      membrane elastic properties. During drying, spheres are deposited
      heterogeneously, but ellipsoids are not. Apparently, increased bending rigidity
      reduces contact line bending and pinning and induces uniform deposition of
      ellipsoids. Surprisingly, suspensions of spheres doped with a small number of
      ellipsoids are also deposited uniformly.

PMID- 23003663
TI  - Topological measure locating the effective crossover between segregation and
      integration in a modular network.
AB  - We introduce an easily computable topological measure which locates the effective
      crossover between segregation and integration in a modular network. Segregation
      corresponds to the degree of network modularity, while integration is expressed
      in terms of the algebraic connectivity of an associated hypergraph. The rigorous
      treatment of the simplified case of cliques of equal size that are gradually
      rewired until they become completely merged, allows us to show that this
      topological crossover can be made to coincide with a dynamical crossover from
      cluster to global synchronization of a system of coupled phase oscillators. The
      dynamical crossover is signaled by a peak in the product of the measures of
      intracluster and global synchronization, which we propose as a dynamical measure
      of complexity. This quantity is much easier to compute than the entropy (of the
      average frequencies of the oscillators), and displays a behavior which closely
      mimics that of the dynamical complexity index based on the latter. The proposed
      topological measure simultaneously provides information on the dynamical
      behavior, sheds light on the interplay between modularity and total integration,
      and shows how this affects the capability of the network to perform both local
      and distributed dynamical tasks.

PMID- 23003664
TI  - Cascading failures in interdependent lattice networks: the critical role of the
      length of dependency links.
AB  - We study the cascading failures in a system composed of two interdependent square
      lattice networks A and B placed on the same Cartesian plane, where each node in
      network A depends on a node in network B randomly chosen within a certain
      distance r from the corresponding node in network A and vice versa. Our results
      suggest that percolation for small r below r(max)~8 (lattice units) is a second
      order transition, and for larger r is a first-order transition. For r<r(max), the
      critical threshold increases linearly with r from 0.593 at r=0 and reaches a
      maximum, 0.738 for r=r(max), and then gradually decreases to 0.683 for
      r=infinity. Our analytical considerations are in good agreement with simulations.
      Our study suggests that interdependent infrastructures embedded in Euclidean
      space become most vulnerable when the distance between interdependent nodes is in
      the intermediate range, which is much smaller than the size of the system.

PMID- 23003665
TI  - Balance between excitation and inhibition controls the temporal organization of
      neuronal avalanches.
AB  - Neuronal avalanches, measured in vitro and in vivo, exhibit a robust critical
      behavior. Their temporal organization hides the presence of correlations. Here we
      present experimental measurements of the waiting time distribution between
      successive avalanches in the rat cortex in vitro. This exhibits a nonmonotonic
      behavior not usually found in other natural processes. Numerical simulations
      provide evidence that this behavior is a consequence of the alternation between
      states of high and low activity, named up and down states, leading to a balance
      between excitation and inhibition controlled by a single parameter. During these
      periods, both the single neuron state and the network excitability level, keeping
      memory of past activity, are tuned by homeostatic mechanisms.

PMID- 23003666
TI  - Associations of forest cover, fragment area, and connectivity with neotropical
      understory bird species richness and abundance.
AB  - Theoretical and empirical studies demonstrate that the total amount of forest and
      the size and connectivity of fragments have nonlinear effects on species
      survival. We tested how habitat amount and configuration affect understory bird
      species richness and abundance. We used mist nets (almost 34,000 net hours) to
      sample birds in 53 Atlantic Forest fragments in southeastern Brazil. Fragments
      were distributed among 3 10,800-ha landscapes. The remaining forest in these
      landscapes was below (10% forest cover), similar to (30%), and above (50%) the
      theoretical fragmentation threshold (approximately 30%) below which the effects
      of fragmentation should be intensified. Species-richness estimates were
      significantly higher (F= 3715, p = 0.00) where 50% of the forest remained, which
      suggests a species occurrence threshold of 30-50% forest, which is higher than
      usually occurs (<30%). Relations between forest cover and species richness
      differed depending on species sensitivity to forest conversion and fragmentation.
      For less sensitive species, species richness decreased as forest cover increased,
      whereas for highly sensitive species the opposite occurred. For sensitive
      species, species richness and the amount of forest cover were positively related,
      particularly when forest cover was 30-50%. Fragment size and connectivity were
      related to species richness and abundance in all landscapes, not just below the
      30% threshold. Where 10% of the forest remained, fragment size was more related
      to species richness and abundance than connectivity. However, the relation
      between connectivity and species richness and abundance was stronger where 30% of
      the landscape was forested. Where 50% of the landscape was forested, fragment
      size and connectivity were both related to species richness and abundance. Our
      results demonstrated a rapid loss of species at relatively high levels of forest
      cover (30-50%). Highly sensitive species were 3-4 times more common above the 30
      50% threshold than below it; however, our results do not support a unique
      fragmentation threshold.

PMID- 23003667
TI  - How many sections are required to clear a tumor? Results from a web-based survey
      of margin thresholds in Mohs micrographic surgery.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) offers an unparalleled cure rate for
      cutaneous malignancy. Its success hinges on achieving reliably negative
      histologic margins. When assessing margins, Mohs surgeons generally examine
      multiple histologic sections per Mohs stage. In some cases, the most-peripheral
      section or sections are clear, but tumor is identified in deeper sections within
      the same tissue block. OBJECTIVE: To explore approaches to margin analysis in
      these scenarios. METHODS: A web-based survey was administered to members of the
      American College of Mohs Surgery investigating their standard practice when
      definitively tumor-free section(s) are examined during a Mohs stage before
      finding cancer in a deep section. Factors influencing the decision were explored.
      RESULTS: The number of clear sections required to declare margin negativity and
      terminate MMS (margin threshold) varied widely among respondents; 25% were
      comfortable with one clear section, whereas 19% would obtain an additional layer
      with eight clear sections. Margin thresholds depended on tumor type but were
      independent of surgeon experience. CONCLUSION: Although no consensus emerged, a
      majority of respondents would not take an additional layer with four clear
      sections if resecting basal cell carcinoma. Prospective outcomes data are needed
      to standardize management of this important oncologic issue.

PMID- 23003668
TI  - Effectiveness of an electronic cognitive aid in patients with acquired brain
      injury: a multicentre randomised parallel-group study.
AB  - The objective of the study was to examine the effectiveness of a customised
      personal digital assistant (PDA) as a cognitive aid for people with acquired
      brain injury, using a randomised parallel-group study. The participants were 34
      patients with acquired brain injury in a cognitive rehabilitation setting. The
      experimental group used a customised PDA, while the control group received care
      as-usual (paper-and-pencil aids). Measurements were conducted at baseline (T0),
      after 8 hours of training (T1), after 16 hours of training (T2), and at 5-month
      follow-up (T3). The main outcome was the attainment of individualised goals. Both
      groups showed a significant increase in goal attainment (GAS) (p < .001). There
      were no significant differences between the groups at T1 or T2 on any of the
      other outcome measures. It was concluded that the customised PDA was as effective
      as paper-and-pencil aids, and may therefore serve as a useful alternative when
      choosing the optimal rehabilitation strategy for a patient.

PMID- 23003669
TI  - Which states enroll their Medicaid-eligible, citizen children with immigrant
      parents?
AB  - OBJECTIVE: To identify which states achieve comparable enrollment rates for
      Medicaid-eligible, citizen children with immigrant and nonimmigrant parents. DATA
      SOURCE: A total of 810,345 Medicaid-eligible, citizen children drawn from the
      2008-2010 American Community Survey. STUDY DESIGN: This study estimates a state
      fixed-effects probit model of uninsured status for Medicaid-eligible, citizen
      children. State and immigrant family interaction variables test whether citizen
      children in immigrant families have a higher probability of remaining uninsured
      compared to children in nonimmigrant families. Simulations predict the uninsured
      rates for Medicaid eligible children in immigrant and nonimmigrant families and
      rank states by the differences between the two groups. PRINCIPAL FINDINGS: While
      some states have insignificant and near zero differences in predicted uninsured
      rates, many states have enrollment disparities reaching 20 percent points between
      citizen children with immigrant and nonimmigrant parents. CONCLUSIONS: Many
      states have large differences in enrollment rates between their Medicaid
      eligible, citizen children with immigrant and nonimmigrant parents. Addressing
      these enrollment disparities could improve the health status of citizen children
      in immigrant families and earn Children's Health Insurance Program
      Reauthorization Act bonus payments for many states.

PMID- 23003670
TI  - Application of three-dimensional culture conditions to human embryonic stem cell
      derived definitive endoderm cells enhances hepatocyte differentiation and
      functionality.
AB  - Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs)
      provide an unlimited source for the generation of human hepatocytes, owing to
      their indefinite self-renewal and pluripotent properties. Both hESC-/iPSC-derived
      hepatocytes hold great promise in treating liver diseases as potential candidates
      for cell replacement therapies or as an in vitro platform to conduct new drug
      trials. It has been previously demonstrated that the initiation of hESC
      differentiation in monolayer cultures increases the generation of definitive
      endoderm (DE) and subsequently of hepatocyte differentiation. However, monolayer
      culture may hinder the maturation of hESC-derived hepatocytes, since such two
      dimensional (2D) conditions do not accurately reflect the complex nature of three
      dimensional (3D) hepatocyte specification in vivo. Here, we report the sequential
      application of 2D and 3D culture systems to differentiate hESCs to hepatocytes.
      Human ESCs were initially differentiated in a monolayer culture to DE cells,
      which were then inoculated into Algimatrix scaffolds. Treatments of hESC-DE cells
      with a ROCK inhibitor before and after inoculation dramatically enhanced their
      survival and the formation of spheroids, which are distinct from HepG2 carcinoma
      cells. In comparison with monolayer culture alone, sequential 2D and 3D cultures
      significantly improved hepatocyte differentiation and function. Our results
      demonstrate that hESC-DE cells can be incorporated into Algimatrix 3D culture
      systems to enhance hepatocyte differentiation and function.

PMID- 23003671
TI  - Fibrin-loaded porous poly(ethylene glycol) hydrogels as scaffold materials for
      vascularized tissue formation.
AB  - Vascular network formation within biomaterial scaffolds is essential for the
      generation of properly functioning engineered tissues. In this study, a method is
      described for generating composite hydrogels in which porous poly(ethylene
      glycol) (PEG) hydrogels serve as scaffolds for mechanical and structural support,
      and fibrin is loaded within the pores to induce vascularized tissue formation.
      Porous PEG hydrogels were generated by a salt leaching technique with 100-150-MUm
      pore size and thrombin (Tb) preloaded within the scaffold. Fibrinogen (Fg) was
      loaded into pores with varying concentrations and polymerized into fibrin due to
      the presence of Tb, with loading efficiencies ranging from 79.9% to 82.4%. Fibrin
      was distributed throughout the entire porous hydrogels, lasted for greater than
      20 days, and increased hydrogel mechanical stiffness. A rodent subcutaneous
      implant model was used to evaluate the influence of fibrin loading on in vivo
      response. At weeks 1, 2, and 3, all hydrogels had significant tissue invasion,
      but no difference in the depth of invasion was found with the Fg concentration.
      Hydrogels with fibrin loading induced more vascularization, with a significantly
      higher vascular density at 20 mg/mL (week 1) and 40 mg/mL (weeks 2 and 3) Fg
      concentration compared to hydrogels without fibrin. In conclusion, we have
      developed a composite hydrogel that supports rapid vascularized tissue ingrowth,
      and thus holds great potential for tissue engineering applications.

PMID- 23003672
TI  - Vitamin D levels and other factors related to bone mineral density during
      pregnancy.
AB  - BACKGROUND: Multiple factors appear to affect bone mineral density (BMD) during
      pregnancy. AIMS: The aim of this study was to determine the relationships between
      BMD of the os calcaneus as measured by quantitative ultrasound (QUS) and levels
      of vitamin D3, parathyroid hormone (PTH), albumin (Alb), calcium (Ca), phosphorus
      (P) and alkaline phosphatase (ALP) in a group of Chinese women. METHODS: Multiple
      parameters, including density of the os calcaneus, were recorded for a group of
      130 women in early (mean gestation, 16.09 +/- 2.65 weeks) and late (mean
      gestation, 32.01 +/- 3.45 weeks) stages of pregnancy; 139 nonpregnant women
      served as controls. RESULTS: Bone mineral density was lower in pregnant women
      than in controls at both early and late stages of pregnancy. Levels of Ca, P and
      ALP were significantly negatively correlated with BMD over the course of
      pregnancy. Levels of D3, PTH and Alb showed a falling trend from early to late
      pregnancy as with QUS BMD of the os calcaneus, but the correlations were not
      statistically significant. CONCLUSIONS: Many factors are correlated with BMD. We
      suggest that levels of Ca and ALP should be included in the routine examination
      of pregnant women.

PMID- 23003674
TI  - Physical origin underlying the entropy loss upon hydrophobic hydration.
AB  - The hydrophobic effect (HE) is commonly associated with the demixing of oil and
      water at ambient conditions and plays the leading role in determining the
      structure and stability of biomolecular assembly in aqueous solutions. On the
      molecular scale HE has an entropic origin. It is believed that hydrophobic
      particles induce order in the surrounding water by reducing the volume of
      configuration space available for hydrogen bonding. Here we show with computer
      simulation results that this traditional picture, based on average structural
      features of hydration water, configurational properties of single water
      molecules, and up to pairwise correlations, is not correct. Analyzing collective
      fluctuations in water clusters we are able to provide a fundamentally new picture
      of HE based on pronounced many-body correlations affecting the switching of
      hydrogen bonds (HBs) between molecules. These correlations emerge as a nonlocal
      compensation of reduced fluctuations of local electrostatic fields in the
      presence of an apolar solute. We propose an alternative view which may also be
      formulated as a maximization principle: The electrostatic noise acting on water
      molecules is maximized under the constraint that each water molecule on average
      maintains as many HBs as possible. In the presence of the solute the maximized
      electrostatic noise is a result of nonlocal fluctuations in the labile HB network
      giving rise to strong correlations among at least up to four water molecules.

PMID- 23003673
TI  - Production of recombineering substrates with standard-size PCR primers.
AB  - Recombineering is a powerful method for DNA manipulation. It has advantages over
      restriction endonuclease-based methods and is usually rapid. Typically,
      recombineering uses long PCR primers (c. 65 bases), each of which contains a
      small region of target homology (c. 45 bases). We have developed a simple, albeit
      somewhat less rapid, strategy to create recombineering substrates that can use
      primers of <= 35 bases for all steps. The regions of homology can be several
      hundred base pairs in length to (1) increase the chance of obtaining the desired
      clone and/or (2) allow coliphage-based recombineering in some non-Escherichia
      coli bacteria. The method uses cloning techniques to construct a template for the
      generation of the recombineering substrate. Because the template is made from
      cloned DNA segments, the segments (including those for the homology regions) can
      be readily changed. During construction of the template plasmid, potential
      background transformants arising from the vector without insert are significantly
      reduced by cloning each segment with two restriction endonucleases that produce
      noncompatible ends. We have used this method to change the bla gene of pACYC177
      to aadA, to add the MCS-lacZalpha region from pBBR1MCS to IncQ plasmid vectors,
      and to make an oriT(IncP) -aacC1 cassette and add it to a plasmid.

PMID- 23003675
TI  - Autophagic subpopulation sorting by sedimentation field-flow fractionation.
AB  - The development of hypoxic areas often takes place in solid tumors and leads
      cells to undergo adaptive signalization like autophagy. This process is
      responsible for misfolded or aggregated proteins and nonfunctional organelle
      recycling, allowing cells to maintain their energetic status. However, it could
      constitute a double-edged pathway leading to both survival and cell death. So, in
      response to stress such as hypoxia, autophagic and apoptotic cells are often
      mixed. To specifically study and characterize autophagic cells and the process,
      we needed to develop a method able to (1) isolate autophagic subpopulation and
      (2) respect apoptotic and autophagic status. Sedimentation field-flow
      fractionation (SdFFF) was first used to monitor physical parameter changes due to
      the hypoxia mimetic CoCl(2) in the p53 mutated SKNBE2(c) human neuroblastoma cell
      line. Second, we showed that "hyperlayer" elution is able to prepare autophagic
      enriched populations, fraction (F3), overexpressing autophagic markers (i.e., LC3
      II accumulation and punctiform organization of autophagosomes as well as
      cathepsin B overactivity). Conversely, the first eluted fraction exhibited
      apoptotic markers (caspase-3 activity and Bax increased expression). For the
      first time, SdFFF was employed as an analytical tool in order to discriminate
      apoptotic and autophagic cells, thus providing an enriched autophagic fraction
      consecutively to a hypoxic stress.

PMID- 23003677
TI  - Novel blue-emitting Na(x)Ca(1-x)Al(2-x)Si(2+x)O8:Eu2+ (x = 0.34) phosphor with
      high luminescent efficiency for UV-pumped light-emitting diodes.
AB  - A novel blue-emitting phosphor, Na(0.34)Ca(0.66)Al(1.66)Si(2.34)O(8):Eu(2+)
      (NCASO:Eu(2+)), was prepared by a wet chemical synthesis method based on the
      hydrolysis of tetraorthosiliate (TEOS) and confirmed the formation of
      NCASO:Eu(2+) from Rietveld analysis. Photoluminescence (PL) results showed that
      the phosphor can be efficiently excited by UV light from 250 to 420 nm, and
      emitted bright broad blue emission, which has maximum intensity at around 445 nm.
      Under 365 nm excitation, the PL emission intensity area of optimized NCASO:Eu(2+)
      was found to be 99.72% of that of a commercial BaMgAl(10)O(17):Eu(2+)
      (BAM:Eu(2+)) phosphor. Moreover, the optical absorbance, internal quantum
      efficiency, and external quantum efficiency of NCASO:Eu(2+) were calculated to be
      112%, 94%, and 105% of that of the commercial BAM:Eu(2+) phosphor, respectively.
      The WLEDs were fabricated using the blue NCASO:Eu(2+) phosphor, a green-emitting
      beta-SiAlON:Eu(2+), and a red-emitting CaAlSiN(3):Eu(2+) phosphors with a near-UV
      chip. The WLED device exhibited an excellent color-rendering index R(a) of 94 at
      a correlated color temperature of 5956 K with CIE coordinates of x = 0.323, y =
      0.335. These results suggest that NCASO:Eu(2+) is a promising blue-emitting
      phosphor for UV LED applications.

PMID- 23003676
TI  - Fall scenarios In causing older women's hip fractures.
AB  - OBJECTIVE: Falls and fall-related injuries among older women constitute a major
      public health problem with huge costs for the society and personal suffering. The
      aim of this study was to describe and illustrate how a number of circumstances,
      conceptualized as a scenario, that were related to the individual, the
      environment, and the ongoing occupation contributed to a fall that led to a hip
      fracture among women. The sample included 48 women over 55 years old. METHODS:
      Interviews were conducted during home visits and the analysis provided a
      descriptive picture of circumstances in the shape of a scenario related to the
      risk of falling. A number of scenarios were developed based on the data and named
      to provide an understanding of the interplay between the individual, the
      environment, and the ongoing occupation at the time of the fall. RESULTS: By
      applying the concept of a scenario, occupational therapists can increase the
      awareness of fall risks among older people, and are relevant also for interior
      designers, architects, and town planners to consider when designing the local
      environment as well as furniture and other objects.

PMID- 23003678
TI  - Use of complementary and alternative medicine in patients with inflammatory bowel
      disease: results of a cross-sectional study in Norway.
AB  - OBJECTIVE: To determine the proportion of complementary and alternative medicine
      (CAM) use in patients with inflammatory bowel disease (IBD) and to identify
      demographic and clinical factors that are associated with CAM use. MATERIAL AND
      METHODS: In this cross-sectional study design, patients with confirmed diagnosis
      of ulcerative colitis (UC) or Crohn's disease (CD), and >=18 years old, attending
      outpatient clinics at 14 hospitals in Norway were eligible to complete
      questionnaires including demographics, clinical variables, and the International
      CAM Questionnaire (I-CAM-Q). RESULTS: Of 460 patients included in the study, 430
      had evaluable questionnaires (response rate 93%). Forty-nine percent (95% CI: 44
      54) had used some type of CAM within the past 12 months. CAM services were
      utilized by 27% (95% CI: 23-31) of the patients, 21% (95% CI: 16-23) reported use
      of CAM products, and 28% (95% CI: 23-31) used CAM self-help practices. The most
      common pattern of CAM use was to combine CAM services and CAM products.
      Significantly, more UC patients (56%) than CD patients (44%) reported CAM use, p
      = 0.03. In UC, only the presence of at least one comorbid condition was directly
      related to CAM use. In CD, being a woman, being aged 31-50 years, having a higher
      education level, and experiencing adverse drug reactions from IBD medication were
      factors independently associated with the use of CAM. CONCLUSION: Use of CAM was
      common among IBD patients attending outpatient clinics. Both demographic and
      clinical factors were associated to CAM use, but the factors differed in their
      significance for UC and CD.

PMID- 23003679
TI  - Association of breastfeeding and exposure to maternal smoking during pregnancy
      with children's general health status later in childhood.
AB  - BACKGROUND: Maternal smoking during pregnancy is associated with a variety of
      risks on fetal health, whereas breastfeeding may protect infants from infections
      in the early postpartum period. Little has been reported regarding their
      associations with children's general health later in childhood. SUBJECTS AND
      METHODS: Parent-rated children's general health status was investigated among
      14,836 children and adolescents 3-17 years old who participated in the German
      Health Interview and Examination Survey for Children and Adolescents (KiGGS) in
      2003-2006. Data on breastfeeding and maternal smoking during pregnancy were
      collected by parent-administered questionnaires. SPSS complex samples logistic
      regression was used to estimate odds ratios (ORs) and 95% confidence intervals
      (95% CIs). RESULTS: Exclusive breastfeeding and non-exposure to maternal smoking
      during pregnancy were associated with better health status overall among all
      children in the KiGGS (both p<0.001). After adjusting for potential confounding
      factors including other prior and current exposures, exclusive breastfeeding over
      6 months remained significant overall among all children (OR 1.21, 95% CI 1.05
      1.38) and in the age groups 7-10 years (OR 1.27, 95% CI 1.01-1.60) and 11-17
      years (OR 1.23, 95% CI 1.01-1.50), while non-exposure to maternal smoking during
      pregnancy remained significant in the age group 11-17 years only (OR 1.49, 95% CI
      1.06-2.10). CONCLUSIONS: Exclusive breastfeeding and non-exposure to maternal
      smoking during pregnancy may be associated with better children's general health
      status later in childhood, particularly when children reach adolescence. Further
      studies are required to elucidate these possible and biologically plausible
      associations. Health professionals should take opportunities to promote
      breastfeeding and cessation of smoking among (expectant) mothers for a healthy
      future of their children.

PMID- 23003680
TI  - Interactions of microbicide nanoparticles with a simulated vaginal fluid.
AB  - The interaction with cervicovaginal mucus presents the potential to impact the
      performance of drug nanocarriers. These systems must migrate through this
      biological fluid in order to deliver their drug payload to the underlying mucosal
      surface. We studied the ability of dapivirine-loaded polycaprolactone (PCL)-based
      nanoparticles (NPs) to interact with a simulated vaginal fluid (SVF)
      incorporating mucin. Different surface modifiers were used to produce NPs with
      either negative (poloxamer 338 NF and sodium lauryl sulfate) or positive
      (cetyltrimethylammonium bromide) surface charge. Studies were performed using the
      mucin particle method, rheological measurements, and real-time multiple particle
      tracking. Results showed that SVF presented rheological properties similar to
      those of human cervicovaginal mucus. Analysis of NP transport indicated mild
      interactions with mucin and low adhesive potential. In general, negatively
      charged NPs underwent subdiffusive transport in SVF, i.e., hindered as compared
      to their diffusion in water, but faster than for positively charged NPs. These
      differences were increased when the pH of SVF was changed from 4.2 to 7.0.
      Diffusivity was 50- and 172-fold lower in SVF at pH 4.2 than in water for
      negatively charged and positively charged NPs, respectively. At pH 7.0, this
      decrease was around 20- and 385-fold, respectively. The estimated times required
      to cross a layer of SVF were equal to or lower than 1.7 h for negatively charged
      NPs, while for positively charged NPs these values were equal to or higher than 7
      h. Overall, our results suggest that negatively charged PCL NPs may be suitable
      to be used as carriers in order to deliver dapivirine and potentially other
      antiretroviral drugs to the cervicovaginal mucosal lining. Also, they further
      reinforce the importance in characterizing the interactions of nanosystems with
      mucus fluids or surrogates when considering mucosal drug delivery.

PMID- 23003681
TI  - Evaluation of sexual function in patients presenting with Behcet's disease with
      or without depression.
AB  - AIM: Sexual dysfunction has been found in many disorders that are chronic or
      disabling. The aim of this study was to evaluate the sexual satisfaction levels,
      sexual function and their relationship with the mental state in a group of
      patients being followed-up with a diagnosis of Behcet's disease (BD). METHOD: A
      total of 50 BD patients and 50 control-group subjects were administered the
      Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS),
      Golombok Rust Sexual Satisfaction Scale (GRISS) and Arizona Sexual Experiences
      Scale (ASEX). RESULTS: The ASEX, GRISS total, HDRS and HARS scores were
      significantly higher in the patient group than the control subjects (P = 0.0001,
      P = 0.007, P = 0.0001, P = 0.0001 respectively). Sexual dissatisfaction was seen
      in 40 (80%) of the patient-group and 16 (32%) of the control-group subjects
      according to the GRISS (P = 0.0001). Female study participants had higher mean
      scores than the control subjects for the ASEX, GRISS total scores and the GRISS
      satisfaction, avoidance, vaginismus and orgasm subscale scores (P = 0.0001, P =
      0.002, P = 0.02, P = 0.001, P = 0.006, P = 0.03 respectively). Male study
      participants had different mean scores for the controls regarding the ASEX scores
      and the GRISS impotence, premature ejaculation, satisfaction and frequency
      subscale scores (P = 0.01, P = 0.01, P = 0.0001, P = 0.03, P = 0.007
      respectively). DISCUSSION: The negative effect of the disorder on the biological
      and functional status and daily living activities in BD patients also influences
      the patients' sexual experiences and satisfaction. The negative effects of
      chronic diseases such as BD should therefore be defined and the disorder
      evaluated from a wide perspective during the treatment process.

PMID- 23003682
TI  - Determination of maslinic acid, a pentacyclic triterpene from olives, in rat
      plasma by high-performance liquid chromatography.
AB  - Maslinic acid, a pentacyclic triterpene from olives, has been reported to exert
      beneficial effects on health, including anticarcinogenic activity. Despite its
      importance, little is known about its bioavailability in both humans and animals.
      A fundamental step for this evaluation consisted of measuring this compound in
      blood. Therefore, a simple high-performance liquid chromatography (HPLC) method
      with diode array detection has been developed. Maslinic acid contained in plasma
      was extracted twice using ethyl acetate. After centrifugation, the organic
      fraction was evaporated to dryness and the residue was reconstituted with
      methanol/water (75:25, v/v) and analyzed by HPLC. The method was validated by
      obtaining a linear correlation (r(2) = 0.999) and an average recovery of 99%.
      Precision expressed as the coefficient of variation ranged from 1.23 to 9.06%.
      The oral administration of maslinic acid (50 mg/kg) to rats and its subsequent
      detection in plasma showed that the method is suitable for absorption,
      distribution, and metabolism studies.

PMID- 23003913
TI  - Bone-to-implant contact around immediately loaded direct laser metal-forming
      transitional implants in human posterior maxilla.
AB  - OBJECTIVE: Direct laser metal forming (DLMF) is a procedure in which a high-power
      laser beam is directed onto a metal powder bed and programmed to fuse particles
      according to a computer-aided design file, generating a thin metal layer. This
      histologic study evaluated the bone-to-implant contact (BIC%) around immediately
      loaded DLMF transitional implants retrieved after 2 months from posterior human
      maxillae. METHODS: Twelve totally edentulous individuals (mean age, 66.14 +/-
      2.11 years) received DLMF transitional implants divided in twelve immediately
      loaded (IL) and twelve unloaded (UI) implants. These transitional implants were
      placed between conventional implants to support the interim complete maxillary
      denture during the healing period. After 8 weeks, the transitional implants and
      the surrounding tissue were removed and prepared for histomorphometric analysis.
      RESULTS: Mature woven preexisting bone lined by newly formed bone in early stages
      of maturation were found around all retrieved implants. Histometric evaluation
      indicated that the mean BIC% was 45.20 +/- 7.68% and 34.10 +/- 7.85% for IL and
      UI, respectively (P <0.05). CONCLUSION: The present data obtained in humans
      showed that, although both IL and UI presented good BIC%, IL DLMF implants had a
      higher BIC% in the posterior maxilla.

PMID- 23003912
TI  - Mast cells in periodontal disease of individuals with and without HIV undergoing
      highly active antiretroviral therapy.
AB  - BACKGROUND: Mast cells appear to be associated with human periodontal disease.
      However, to the best of our knowledge, no studies have evaluated the presence of
      mast cells in individuals with human immunodeficiency virus (HIV) undergoing
      highly active antiretroviral therapy (HAART). METHODS: Gingival samples were
      obtained from 50 individuals with and without HIV who presented with chronic
      gingivitis and periodontitis. Immunohistochemical staining was performed to
      identify c-kit and tryptase mast cells. Inflammatory infiltrate was evaluated and
      quantified in the specimens of gingival tissue. In the inflammatory infiltrate
      subjacent to the pocket epithelium, the densities of the mast cells were
      calculated. These results were compared between the groups with and without HIV.
      Correlations could be drawn between the densities of c-kit and tryptase mast
      cells and the density of inflammatory infiltrate, cluster of differentiation 4
      (CD4)-positive and CD8(+) T-lymphocyte levels, and viral loads. RESULTS: Although
      the individuals with HIV had higher densities of c-kit or tryptase mast cells
      than those without HIV, both groups presented with chronic gingivitis or
      periodontitis, and no statistically significant differences could be observed.
      Both strong and negative correlations could be observed among the inflammatory
      infiltrate, c-kit, and tryptase in individuals both with and without HIV.
      Concerning the chronic gingivitis of the individuals with HIV, both strong and
      positive correlations could be observed between the density of c-kit and CD8(+) T
      lymphocyte levels. CONCLUSIONS: Individuals with HIV undergoing HAART, compared
      with individuals without HIV, had no statistically significant differences in
      mast cell densities in gingival tissue.

PMID- 23003914
TI  - Aggressive periodontitis defined by recursive partitioning analysis of
      immunologic factors.
AB  - BACKGROUND: The present study aims to extend recent findings of a non-linear
      model of the progression of periodontitis supporting the notion that aggressive
      periodontitis (AgP) and chronic periodontitis (CP) are distinct clinical
      entities. This approach is based on the implementation of recursive partitioning
      analysis (RPA) to evaluate a series of immunologic parameters acting as
      predictors of AgP and CP. METHODS: RPA was applied to three population samples,
      that were retrieved from previous studies, using 17 immunologic parameters. The
      mean values of the parameters in control subjects were used as the cut-off
      points. Leave-one-out cross-validation (LOOCV) prediction errors were estimated
      in the proposed models, as well as the Kullback-Leibler divergence (DKL) of the
      distribution of positive results in AgP compared to CP and negative results in CP
      compared to AgP. RESULTS: Seven classification trees were derived showing that
      the relationship of interleukin (IL)-4, IL-1, IL-2 has the highest potential to
      rule out or rule in AgP. On the other hand, immunoglobulin (Ig)A, IgM used to
      rule out AgP and cluster of differentiation 4 (CD4)/CD8, CD20 used to rule in AgP
      showed the least LOOCV cost. Penalizing DKL with LOOCV cost promotes the IL-4, IL
      1, IL-2 model for ruling out AgP, whereas the single CD4/CD8 ratio with a lowered
      discrimination cut-off point was used to rule in AgP. CONCLUSIONS: Although a
      test is unlikely to have both high sensitivity and high specificity, the use of
      immunologic parameters in the right model can efficiently complement a clinical
      examination for ruling out or ruling in AgP.

PMID- 23003915
TI  - Doxycycline-loaded beta-tricalcium phosphate release following EDTA root surface
      etching improved the clinical outcomes in chronic periodontitis: an in vivo
      study.
AB  - BACKGROUND: The main objective of the present study is to quantify doxycycline
      (DOX) release from beta-tricalcium phosphate (beta-TCP) after EDTA root surface
      treatment. METHODS: Thirty systemically healthy patients with >=1 paired
      contralateral interproximal intrabony defect >=4 mm deep along with an
      interproximal probing depth >=6 mm and clinical attachment level >=4 mm were
      randomized into two groups. Group 1 (G1) consisted of sites treated with open
      flap debridement followed by placement of DOX blended with beta-TCP (DOX-beta
      TCP), whereas group 2 (G2) sites were treated with flap surgery followed by the
      placement of DOX blended with beta-TCP after EDTA etching of the exposed root
      surfaces (DOX-beta-TCP + EDTA). Samples of gingival crevicular fluid (GCF) were
      obtained 1, 3, 7, 14, and 21 days after surgery. Quantitative measurements of DOX
      were taken with high-performance liquid chromatography. Clinical evaluation and
      follow-up for 6 months were performed. RESULTS: At 21 days, the DOX-beta-TCP +
      EDTA-treated group showed a 194.7 ug/mL value. The DOX-beta-TCP + EDTA-treated
      group retained more DOX during the periods of 3, 7, 10, 14, and 21 days than the
      DOX-beta-TCP-treated group. Six months after therapy, DOX-beta-TCP + EDTA-treated
      sites showed more significant clinical improvements compared to DOX-beta-TCP
      treated sites (P <= 0.05). CONCLUSIONS: EDTA root surface etching enhances DOX
      availability in the GCF following its release from beta-TCP as a drug carrier.

PMID- 23003916
TI  - Enhancing guided tissue regeneration of periodontal defects by using a novel
      perforated barrier membrane.
AB  - BACKGROUND: The present study was designed to determine whether exclusion of the
      gingival connective tissue (CT) and periosteum with contained stem cells has a
      positive or negative effect on periodontal regeneration by comparing the use of a
      novel modified perforated collagen membrane with a traditional cell occlusive
      barrier membrane. METHODS: Twenty non-smoking patients with severe chronic
      periodontitis were included in the study. Single deep intrabony defects from each
      of the patients were randomly divided into two groups, as follows: occlusive
      bovine collagen membranes (OM control group, 10 sites) and modified perforated
      bovine collagen membranes (MPM test group, 10 sites). Plaque index, gingival
      index, probing depth (PD), clinical attachment level (CAL), defect base level
      (DBL), and crestal bone level (CBL) were measured at baseline and were reassessed
      at 6 and 9 months after therapy to evaluate the quantitative changes in the
      defect. RESULTS: At 6- and 9-month observation periods, the MPM-treated sites
      showed a statistically significant improvement in PD reduction and CAL gain
      compared with the OM control group. DBL was significantly reduced with no
      significant difference between the two groups at 6- and 9-month observation
      periods. CBL was significantly higher in the MPM group when compared with that of
      the OM group at both observation periods. The postoperative differences between
      the two groups were 2 and 1.7 mm at 6 and 9 months, respectively, in favor of the
      MPM-treated sites. CONCLUSIONS: The present study demonstrated enhanced clinical
      outcomes when using novel MPMs compared to OMs in guided tissue regeneration
      procedures. These results may be affected by the penetration of gingival CT
      contained stem cells and periosteal cells and their differentiation into
      components of the attachment apparatus.

PMID- 23003917
TI  - Initial periodontal treatment for prevention of chronic obstructive pulmonary
      disease exacerbations.
AB  - BACKGROUND: Infective exacerbations in patients with chronic obstructive
      pulmonary disease (COPD) are associated with increased mortality. Therefore,
      effective management of COPD should include prevention and reduction of
      exacerbations. The oral cavity is an important reservoir for the respiratory
      pathogens and these pathogens can be aspirated into the lower respiratory tract,
      increasing the risk of respiratory infection. Periodontal therapy may reduce
      these pathogens colonized on the surfaces of teeth and thus may reduce the
      frequency of COPD exacerbations. The authors aim to assess the effect of initial
      periodontal therapy on exacerbation frequency in COPD patients. METHODS: The
      authors conducted a prospective, controlled group trial of initial periodontal
      treatment in 40 patients with COPD with chronic periodontitis (CP) and a history
      of >=1 infective exacerbation in the previous year. Number of exacerbations in
      the previous year was recorded. Patients were divided into two groups; the test
      group (n = 20) included patients who had initial periodontal treatment, and the
      control group (n = 20) included patients who did not have periodontal therapy.
      Number of exacerbations during the following 12 months was noted. Periodontal
      parameters were measured at baseline and 6 and 12 months. RESULTS: The test group
      showed a significant reduction in the exacerbation frequency during the follow-up
      period (P = 0.01). Although median exacerbations declined from 3 to 2 in the test
      group, they increased from 2 to 3 in the control group. CONCLUSION: Initial
      periodontal therapy in patients with COPD with CP may decrease the exacerbation
      frequency.

PMID- 23003918
TI  - Induction of toll-like receptor expression by Porphyromonas gingivalis.
AB  - BACKGROUND: Toll-like receptors (TLRs) play pivotal roles in host immune
      responses and have been suggested to be involved in the development of many
      infectious diseases. In this study, the mRNA expression levels of TLR2, TLR4, and
      TLR9 and their relationship with periodontopathic bacteria in periodontal tissue
      are examined. Furthermore, the mechanism of TLR induction by Porphyromonas
      gingivalis is investigated in human gingival fibroblasts (HGFs). METHODS:
      Gingival tissue and subgingival plaque samples were collected from 19 patients
      with chronic periodontitis (CP) and 16 control individuals without periodontitis.
      Gene expression levels in the tissues and in HGFs were analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR). The numbers of periodontopathic
      bacteria were determined by quantitative real-time PCR. RESULTS: The expression
      levels of TLR2 and TLR9 were significantly higher in the tissues of patients with
      CP compared to the tissues of control individuals. The mRNA levels of TLR2 and
      TLR9, but not TLR4, were positively correlated with the number of P. gingivalis
      in subgingival plaque. P. gingivalis sonicated extract, P. gingivalis
      lipopolysaccharide, P. gingivalis DNA, and tumor necrosis factor-alpha(TNF-alpha)
      could significantly upregulate the mRNA expression of TLR2 in HGFs. Furthermore,
      P. gingivalis-mediated TLR2 expression was suppressed by TNF-alpha antibody.
      CONCLUSIONS: This study suggests that P. gingivalis infection induces TLR2 and
      TLR9 upregulation in patients with CP. P. gingivalis-induced TLR2 expression in
      HGFs is partially dependent on TNF-alpha and may lead to sensitization of HGFs to
      bacterial components encountered in the periodontal microenvironment.

PMID- 23003919
TI  - Comparative studies on microvascular endothelial cells isolated from periodontal
      tissue.
AB  - BACKGROUND: Most available periodontal studies regarding the endothelial cell
      (EC) were investigated by using human umbilical vein endothelial cells (HUVECs);
      however, ECs can display remarkable heterogeneity in vascular beds of different
      origins. The aim of the present study, therefore, is to characterize
      microvascular ECs isolated from periodontal tissue and investigate their growth
      and gene expression compared to HUVECs (macrovascular). METHODS: Periodontal
      ligament ECs (PDL-ECs) and gingiva ECs (G-ECs) were isolated by coupling to
      monoclonal anti-CD31 antibody magnetic beads. Both PDL-ECs and G-ECs were
      characterized to definitively demonstrate that the culture represented pure ECs.
      Their growth was determined by resazurin reduction assay. Interleukin (IL)-8,
      intercellular adhesion molecule 1 (ICAM-1), and E-selectin gene expression were
      determined by real-time quantitative reverse-transcription polymerase chain
      reaction after treatment with Escherichia coli lipopolysaccharide (LPS). RESULTS:
      PDL-ECs and G-ECs revealed specific EC characteristics but formed tube-like
      structures and had slower growth rates than HUVECs. After E. coli LPS treatment,
      PDL-ECs and G-ECs showed similar dose-dependently increased levels of IL-8, ICAM
      1, and E-selectin mRNA expression; however, their expressions were in contrast to
      HUVECs. PDL-ECs and G-ECs showed obviously increased ICAM-1 mRNA expression,
      whereas HUVECs showed markedly increased E-selectin mRNA expression after
      treatment with 0.1 MUg/mL E. coli LPS. CONCLUSIONS: ECs isolated from periodontal
      tissue show different growth and gene expression from those of HUVECs. Thus,
      these microvascular ECs appear to be a more valuable in vitro model system than
      HUVECs (macrovascular) to further study pathogenesis and angiogenesis of
      periodontal disease.

PMID- 23003920
TI  - Comparison of surgical stripping; erbium-doped:yttrium, aluminum, and garnet
      laser; and carbon dioxide laser techniques for gingival depigmentation: a
      clinical and histologic study.
AB  - BACKGROUND: Gingival melanin depigmentation procedures are commonly associated
      with recurrence of pigmentation, which starts with migration of melanocytes from
      the adjacent free gingiva. The extent and rate of recurrence varies according to
      the treatment modalities used and duration of follow-up. The aim of this study is
      to compare the surgical stripping; carbon dioxide (CO2); and erbium
      doped:yttrium, aluminum, and garnet (Er:YAG) laser techniques for gingival
      depigmentation and to evaluate their effect on histologic changes in melanocyte
      activity and clinical repigmentation. METHODS: In this study, 140 sites from 35
      patients with bilateral melanin hyperpigmentation were treated with surgical
      stripping (two sites per patient), "epithelial-peel" (CO2 laser, 2 to 4 W,
      continuous wave),and "brushstroke" (Er:YAG laser, 180 mJ, 10 Hz, long pulse)
      techniques. Surgical microscope monitoring was performed intraoperatively.
      Patient preference and perception of pain, change in Dummett oral pigmentation
      index (DOPI), Hedin index, and change in area of pigmentation from baseline to 6
      months postoperatively were recorded. Twenty samples each from the three
      treatment modalities were selected for histologic analysis using hematoxylin and
      eosin and dihydroxyphenylalanine oxidase special stains. RESULTS: At the 6-month
      postoperative visit, 15 of 70 (21.4%) and three of 20 (15%) of the surgical
      treated; 10 of 35 (28.6%) and six of 20 (30%) of the Er:YAG-laser-treated; and
      eight of 35 (22.8%) and four of 20 (20%) of the CO2-laser-treated sites showed
      clinical and histologic repigmentation, respectively. Paired t test, analysis of
      variance, and chi(2) tests were used for statistical analyses. P values for
      comparison of microscopic evaluation, change in DOPI, Hedin index, and area of
      pigmentation were 0.001, which were statistically significant. Comparison for
      patient preference and pain indices gave statistically significant values for
      Er:YAG laser depigmentation (P = 0.001). CONCLUSIONS: Clinical repigmentation
      after gingival depigmentation is an outcome of histologic changes in the
      melanocyte activity and density of the melanin pigments. Surgical stripping for
      gingival depigmentation remains the gold standard; however, Er:YAG laser and CO2
      lasers can be effectively used but with distinct differences.

PMID- 23003921
TI  - CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic
      syndrome characteristics and monounsaturated fat intake.
AB  - The circadian clock system instructs 24-h rhythmicity on gene expression in
      essentially all cells, including adipocytes, and epigenetic mechanisms may
      participate in this regulation. The aim of this research was to investigate the
      influence of obesity and metabolic syndrome (MetS) features in clock gene
      methylation and the involvement of these epigenetic modifications in the
      outcomes. Sixty normal-weight, overweight and obese women followed a 16-weeks
      weight reduction program. DNA methylation levels at different CpG sites of CLOCK,
      BMAL1 and PER2 genes were analyzed by Sequenom's MassARRAY in white blood cells
      obtained before the treatment. Statistical differences between normal-weight and
      overweight + obese subjects were found in the methylation status of different CpG
      sites of CLOCK (CpGs 1, 5-6, 8 and 11-14) and, with lower statistical
      significance, in BMAL1 (CpGs 6-7, 8, 15 and 16-17). The methylation pattern of
      different CpG sites of the three genes showed significant associations with
      anthropometric parameters such as body mass index and adiposity, and with a MetS
      score. Moreover, the baseline methylation levels of CLOCK CpG 1 and PER2 CpGs 2-3
      and 25 correlated with the magnitude of weight loss. Interestingly, the
      percentage of methylation of CLOCK CpGs 1 and 8 showed associations with the
      intake of monounsaturated and polyunsaturated fatty acids. This study
      demonstrates for the first time an association between methylation status of CpG
      sites located in clock genes (CLOCK, BMAL1 and PER2) with obesity, MetS and
      weight loss. Moreover, the methylation status of different CpG sites in CLOCK and
      PER2 could be used as biomarkers of weight-loss success, particularly CLOCK CPGs
      5-6.

PMID- 23003923
TI  - The biologically effective dose in inhalation nanotoxicology.
AB  - In all branches of toxicology, the biologically effective dose (BED) is the
      fraction of the total dose of a toxin that actually drives any toxic effect.
      Knowledge of the BED has a number of applications including in building structure
      activity relationships, the selection of metrics, the design of safe particles,
      and the determination of when a nanoparticle (NP) can be considered to be "new"
      for regulatory purposes. In particle toxicology, we define the BED as "the entity
      within any dose of particles in tissue that drives a critical pathophysiogically
      relevant form of toxicity (e.g., oxidative stress, inflammation, genotoxicity, or
      proliferation) or a process that leads to it." In conventional chemical
      toxicology, researchers generally use the mass as the metric to describe dose
      (such as mass per unit tissue or cells in culture) because of its convenience.
      Concentration, calculated from mass, may also figure in any description of dose.
      In the case of a nanoparticle dose, researchers use either the mass or the
      surface area. The mass of nanoparticles is not the only driver of their activity:
      the surfaces of insoluble particles interact with biological systems, and soluble
      nanoparticles can release factors that interact with these systems. Nanoparticle
      shape can modify activity. In this Account, we describe the current knowledge of
      the BED as it pertains to different NP types. Soluble toxins released by NPs
      represent one potential indicator of BED for wholly or partially soluble NPs
      composed of copper or zinc. Rapid dissolution of these NPs into their toxic ions
      in the acidic environment of the macrophage phagolysosome causes those ions to
      accumulate, which leads to lysosome destabilization and inflammation. In
      contrast, soluble NPs that release low toxicity ions, such as magnesium oxide
      NPs, are not inflammogenic. For insoluble NPs, zeta potential can serve as a BED
      measurement because the exposure of the particle surface to the acidic milieu of
      the phagolysosome and interactions with the lysosomal membrane can compromise the
      integrity of the NPs. Researchers have explored oxidative potential of NPs most
      extensively as an indicator of the BED: the ability of an NP to cause oxidative
      stress in cells is a key factor in determining cell toxicity, inflammogenicity,
      and oxidative DNA adduct formation. Finally we discuss BEDs for high aspect ratio
      nanoparticles because long fibers or nanoplatelets can cause inflammation and
      further effects. These consequences arise from the paradoxically small
      aerodynamic diameter of fibers or thin platelets. As a result, these NPs can
      deposit beyond the ciliated airways where their extended dimensions prevent them
      from being fully phagocytosed by macrophages, leading to frustrated phagocytosis.
      Although knowledge is accumulating on the BED for NPs, many questions and
      challenges remain in understanding and utilizing this important nanotoxicological
      parameter.

PMID- 23003924
TI  - Ziv-Zakai error bounds for quantum parameter estimation.
AB  - I propose quantum versions of the Ziv-Zakai bounds as alternatives to the widely
      used quantum Cramer-Rao bounds for quantum parameter estimation. From a simple
      form of the proposed bounds, I derive both a Heisenberg error limit that scales
      with the average energy and a limit similar to the quantum Cramer-Rao bound that
      scales with the energy variance. These results are further illustrated by
      applying the bound to a few examples of optical phase estimation, which show that
      a quantum Ziv-Zakai bound can be much higher and thus tighter than a quantum
      Cramer-Rao bound for states with highly non-gaussian photon-number statistics in
      certain regimes and also stay close to the latter where the latter is expected to
      be tight.

PMID- 23003925
TI  - Observation of the intrinsic Abraham force in time-varying magnetic and electric
      fields.
AB  - The Abraham force exerted by a time-dependent electromagnetic field on neutral,
      polarizable matter has two contributions. The one induced by a time-varying
      magnetic field and a static electric field is reported here for the first time.
      We discuss our results in the context of the radiative momentum in matter. Our
      observations are consistent with Abraham's and Nelson's versions for radiative
      momentum.

PMID- 23003922
TI  - RNA interference-mediated phosphodiesterase 4D splice variants knock-down in the
      prefrontal cortex produces antidepressant-like and cognition-enhancing effects.
AB  - BACKGROUND AND PURPOSE: Phosphodiesterase 4 (PDE4) inhibitors produce potent
      antidepressant-like and cognition-enhancing effects. However, their clinical
      utility is limited by the major side effect of emesis, which appears to be PDE4
      isoform-specific. Although PDE4D subtype plays the pivotal role in these
      therapeutic profiles, it is also the primary subtype responsible for emesis.
      Therefore, the aim of present research was to investigate whether long-form PDE4D
      variants mediate antidepressant-like and cognition-enhancing effects, but are
      irrespective with emesis. EXPERIMENTAL APPROACH: In mice microinfused with
      lentiviral vectors that contained shRNA-mir hairpin structure targeting long-form
      PDE4Ds into bilateral prefrontal cortices, the tail-suspension and forced-swim
      tests were used to measure antidepressant-like effects; novel object recognition
      and Morris water-maze tasks were used to determine cognition-enhancing effects.
      The emetic potential was assessed by alpha2 adrenergic receptor-mediated
      anaesthesia, a surrogate measure of emesis. Intracellular cAMP signalling was
      analysed by time-resolved FRET immunoassay and Western-blot. Dendritic complexity
      was assessed by Golgi staining. KEY RESULTS: Microinfusions of lentiviral PDE4D
      shRNA down-regulated PDE4D4 and PDE4D5, and imitated the antidepressant-like and
      cognition-enhancing effects of the prototypical PDE4 inhibitor rolipram. The
      behavioural effects were related to dendritic complexity and mediated by the
      increased cAMP signalling. In addition, these effects were not enhanced in the
      presence of rolipram. Finally, while rolipram shortened the duration of combined
      anaesthesia, RNA interference-mediated PDE4D knock-down in the prefrontal cortex
      did not. CONCLUSION AND IMPLICATIONS: These data suggest that long-form PDE4Ds,
      at least PDE4D4 and PDE4D5, may be the promising targets for the development of
      PDE4 variant-selective inhibitors as the new pharmacotherapies for depressive
      disorders and neurodegenerative diseases involving memory deficits.

PMID- 23003926
TI  - Spontaneous emission by rotating objects: a scattering approach.
AB  - We study the quantum electrodynamics vacuum in the presence of a body rotating
      along its axis of symmetry and show that the object spontaneously emits energy if
      it is lossy. The radiated power is expressed as a general trace formula solely in
      terms of the scattering matrix, making an explicit connection to the conjecture
      of Zel'dovich [JETP Lett. 14, 180 (1971)] on rotating objects. We further show
      that a rotating body drags along nearby objects while making them spin parallel
      to its own rotation axis.

PMID- 23003927
TI  - Force-free gravitational redshift: proposed gravitational Aharonov-Bohm
      experiment.
AB  - We propose a feasible laboratory interferometry experiment with matter waves in a
      gravitational potential caused by a pair of artificial field-generating masses.
      It will demonstrate that the presence of these masses (and, for moving atoms,
      time dilation) induces a phase shift, even if it does not cause any classical
      force. The phase shift is identical to that produced by the gravitational
      redshift (or time dilation) of clocks ticking at the atom's Compton frequency. In
      analogy to the Aharonov-Bohm effect in electromagnetism, the quantum mechanical
      phase is a function of the gravitational potential and not the classical forces.

PMID- 23003928
TI  - Observing quantum oscillation of ground states in single molecular magnet.
AB  - Single molecular magnets (SMMs) are among the potential systems for quantum
      memory and quantum information processing. Quantum coherence and oscillation are
      critical for these applications. The ground-state quantum coherence and Rabi
      oscillations of the SMM V15 ([V15(IV)As6(III)O42(H2O)]6-) have been studied in
      this context. We have affirmatively measured at 2.4 K the Rabi quantum
      oscillations and coherence time T2 for the ground states of the V15 ion of
      collective spin S=1/2, in addition to confirming the previously reported results
      for the S=3/2 excited states. The oscillations of S=3/2 and S=1/2 states are of
      different frequencies, and so can be separately selected for purposive
      manipulations. T2 of 188+/-4  ns (S=3/2) and 149+/-10  ns (S=1/2) are much less
      than T1~12  MUs and are further extendible via various approaches for qubit
      implementations.

PMID- 23003930
TI  - Discrete Fourier-based correlations for entanglement detection.
AB  - We introduce two forms of correlations on two d-level (qudit) systems for
      entanglement detection. The correlations can be measured via experimentally
      tractable two local measurement settings and their separable bounds are
      determined by discrete Fourier-based uncertainty relations. They are useful to
      estimate lower bounds of the Schmidt number in order to clarify generation of a
      genuine qudit entanglement. We also present inseparable conditions for multiqudit
      systems associated with the qudit stabilizer formalism as another role of the
      correlations on the inseparability problem.

PMID- 23003929
TI  - Quantifying tripartite entanglement of three-qubit generalized Werner states.
AB  - Multipartite entanglement is a key concept in quantum mechanics for which,
      despite the experimental progress in entangling three or more quantum devices,
      there is still no general quantitative theory that exists. In order to
      characterize the robustness of multipartite entanglement, one often employs
      generalized Werner states, that is, mixtures of a Greenberger-Horne-Zeilinger
      (GHZ) state and the completely unpolarized state. While two-qubit Werner states
      have been instrumental for various important advancements in quantum information,
      as of now there is no quantitative account for such states of more than two
      qubits. By using the GHZ symmetry introduced recently, we find exact results for
      tripartite entanglement in three-qubit generalized Werner states and, moreover,
      the entire family of full-rank mixed states that share the same symmetries.

PMID- 23003931
TI  - Quasilocality and efficient simulation of markovian quantum dynamics.
AB  - We consider open many-body systems governed by a time-dependent quantum master
      equation with short-range interactions. With a generalized Lieb-Robinson bound,
      we show that the evolution in this very generic framework is quasilocal; i.e.,
      the evolution of observables can be approximated by implementing the dynamics
      only in a vicinity of the observables' support. The precision increases
      exponentially with the diameter of the considered subsystem. Hence, time
      evolution can be simulated on classical computers with a cost that is independent
      of the system size. Providing error bounds for Trotter decompositions, we
      conclude that the simulation on a quantum computer is additionally efficient in
      time. For experiments and simulations in the Schrodinger picture, our result can
      be used to rigorously bound finite-size effects.

PMID- 23003932
TI  - Asymptotic dynamics of coined quantum walks on percolation graphs.
AB  - Quantum walks obey unitary dynamics: they form closed quantum systems. The system
      becomes open if the walk suffers from imperfections represented as missing links
      on the underlying basic graph structure, described by dynamical percolation.
      Openness of the system's dynamics creates decoherence, leading to strong mixing.
      We present a method to analytically solve the asymptotic dynamics of coined,
      percolated quantum walks for a general graph structure. For the case of a circle
      and a linear graph we derive the explicit form of the asymptotic states. We find
      that a rich variety of asymptotic evolutions occur: not only the fully mixed
      state, but other stationary states; stable periodic and quasiperiodic
      oscillations can emerge, depending on the coin operator, the initial state, and
      the topology of the underlying graph.

PMID- 23003933
TI  - Adiabatic quantum algorithm for search engine ranking.
AB  - We propose an adiabatic quantum algorithm for generating a quantum pure state
      encoding of the PageRank vector, the most widely used tool in ranking the
      relative importance of internet pages. We present extensive numerical simulations
      which provide evidence that this algorithm can prepare the quantum PageRank state
      in a time which, on average, scales polylogarithmically in the number of web
      pages. We argue that the main topological feature of the underlying web graph
      allowing for such a scaling is the out-degree distribution. The top-ranked log(n)
      entries of the quantum PageRank state can then be estimated with a polynomial
      quantum speed-up. Moreover, the quantum PageRank state can be used in "q
      sampling" protocols for testing properties of distributions, which require
      exponentially fewer measurements than all classical schemes designed for the same
      task. This can be used to decide whether to run a classical update of the
      PageRank.

PMID- 23003935
TI  - Constraints on measurement-based quantum computation in effective cluster states.
AB  - The aim of this work is to study the physical properties of a one-way quantum
      computer in an effective low-energy cluster state. We calculate the optimal
      working conditions as a function of the temperature and of the system parameters.
      The central result of our work is that any effective cluster state implemented in
      a perturbative framework is fragile against special kinds of external
      perturbations. Qualitative aspects of our work are important for any
      implementation of effective low-energy models containing strong multisite
      interactions.

PMID- 23003934
TI  - Detecting incapacity of a quantum channel.
AB  - Using unreliable or noisy components for reliable communication requires error
      correction. But which noise processes can support information transmission, and
      which are too destructive? For classical systems any channel whose output depends
      on its input has the capacity for communication, but the situation is
      substantially more complicated in the quantum setting. We find a generic test for
      incapacity based on any suitable forbidden transformation--a protocol for
      communication with a channel passing our test would also allow one to implement
      the associated forbidden transformation. Our approach includes both known quantum
      incapacity tests--positive partial transposition and antidegradability (no
      cloning)--as special cases, putting them both on the same footing.

PMID- 23003936
TI  - Measurements of quasiparticle tunneling dynamics in a band-gap-engineered
      transmon qubit.
AB  - We have engineered the band gap profile of transmon qubits by combining oxygen
      doped Al for tunnel junction electrodes and clean Al as quasiparticle traps to
      investigate energy relaxation due to quasiparticle tunneling. The relaxation time
      T1 of the qubits is shown to be insensitive to this band gap engineering.
      Operating at relatively low-E(J)/E(C) makes the transmon transition frequency
      distinctly dependent on the charge parity, allowing us to detect the
      quasiparticles tunneling across the qubit junction. Quasiparticle kinetics have
      been studied by monitoring the frequency switching due to even-odd parity change
      in real time. It shows the switching time is faster than 10  MUs, indicating
      quasiparticle-induced relaxation has to be reduced to achieve T1 much longer than
      100  MUs.

PMID- 23003937
TI  - Anomalous spatial diffusion and multifractality in optical lattices.
AB  - The transport of cold atoms in shallow optical lattices is characterized by slow,
      nonstationary momentum relaxation. We develop a projector operator method able to
      derive, in this case, a generalized Smoluchowski equation for the position
      variable. We show that this explicitly non-markovian equation can be written as a
      systematic expansion involving higher-order derivatives. We use the latter to
      compute arbitrary moments of the spatial distribution and analyze their
      multifractal properties.

PMID- 23003938
TI  - Theory of fractional Levy kinetics for cold atoms diffusing in optical lattices.
AB  - Recently, anomalous superdiffusion of ultracold 87Rb atoms in an optical lattice
      has been observed along with a fat-tailed, Levy type, spatial distribution. The
      anomalous exponents were found to depend on the depth of the optical potential.
      We find, within the framework of the semiclassical theory of Sisyphus cooling,
      three distinct phases of the dynamics as the optical potential depth is lowered:
      normal diffusion; Levy diffusion; and x~t(3/2) scaling, the latter related to
      Obukhov's model (1959) of turbulence. The process can be formulated as a Levy
      walk, with strong correlations between the length and duration of the excursions.
      We derive a fractional diffusion equation describing the atomic cloud, and the
      corresponding anomalous diffusion coefficient.

PMID- 23003939
TI  - Neutrino emission from gamma-ray burst fireballs, revised.
AB  - We review the neutrino flux from gamma-ray bursts, which is estimated from gamma
      ray observations and used for the interpretation of recent IceCube data, from a
      particle physics perspective. We numerically calculate the neutrino flux for the
      same astrophysical assumptions as the analytical fireball neutrino model,
      including the dominant pion and kaon production modes, flavor mixing, and
      magnetic field effects on the secondary muons, pions, and kaons. We demonstrate
      that taking into account the full energy dependencies of all spectra, the
      normalization of the expected neutrino flux reduces by about one order of
      magnitude and the spectrum shifts to higher energies, where we can pin down the
      exact origin of the discrepancies by the recomputation of the analytical models.
      We also reproduce the IceCube-40 analysis for exactly the same bursts and same
      assumptions and illustrate the impact of uncertainties. We conclude that the
      baryonic loading of the fireballs, which is an important control parameter for
      the emission of cosmic rays, can be constrained significantly with the full-scale
      experiment after about ten years.

PMID- 23003940
TI  - Instability in the dense supernova neutrino gas with flavor-dependent angular
      distributions.
AB  - The usual description of self-induced flavor conversions for neutrinos (nu's) in
      supernovae is based on the simplified assumption that all the nu's of the
      different species are emitted "half-isotropically" by a common neutrinosphere, in
      analogy to a blackbody emission. However, realistic supernova simulations show
      that nu angular distributions at decoupling are far from being half-isotropic
      and, above all, are flavor dependent. We show that flavor-dependent angular
      distributions may lead to crossing points in the angular spectra of different nu
      species (where F(nu(e))=F(nu(x)) and F(nu(e))=F(nu(x))) around which a new
      multiangle instability can develop. To characterize this effect, we carry out a
      linearized flavor stability analysis for different supernova neutrino angular
      distributions. We find that this instability can shift the onset of the flavor
      conversions toward low radii and produce a smearing of the splitting features
      found with trivial nu emission models. As a result the spectral differences among
      nu's of different flavors could be strongly reduced.

PMID- 23003941
TI  - Bounds on spectral dispersion from Fermi-detected gamma ray bursts.
AB  - Data from four Fermi-detected gamma-ray bursts (GRBs) are used to set limits on
      spectral dispersion of electromagnetic radiation across the Universe. The
      analysis focuses on photons recorded above 1 GeV for Fermi-detected GRB 080916C,
      GRB 090510A, GRB 090902B, and GRB 090926A because these high-energy photons yield
      the tightest bounds on light dispersion. It is shown that significant photon
      bunches in GRB 090510A, possibly classic GRB pulses, are remarkably brief, an
      order of magnitude shorter in duration than any previously claimed temporal
      feature in this energy range. Although conceivably a>3sigma fluctuation, when
      taken at face value, these pulses lead to an order of magnitude tightening of
      prior limits on photon dispersion. Bound of Deltac/c<6.94*10(-21) is thus
      obtained. Given generic dispersion relations where the time delay is proportional
      to the photon energy to the first or second power, the most stringent limits on
      the dispersion strengths were k1<1.61*10(-5)  sec Gpc(-1) GeV(-1) and k2<3.57*10(
      7)  sec Gpc(-1) GeV(-2), respectively. Such limits constrain dispersive effects
      created, for example, by the spacetime foam of quantum gravity. In the context of
      quantum gravity, our bounds set M1c(2) greater than 525 times the Planck mass,
      suggesting that spacetime is smooth at energies near and slightly above the
      Planck mass.

PMID- 23003942
TI  - Revising the multipole moments of numerical spacetimes and its consequences.
AB  - Identifying the relativistic multipole moments of a spacetime of an astrophysical
      object that has been constructed numerically is of major interest, both because
      the multipole moments are intimately related to the internal structure of the
      object, and because the construction of a suitable analytic metric that mimics a
      numerical metric should be based on the multipole moments of the latter one in
      order to yield a reliable representation. In this Letter, we show that there has
      been a widespread delusion in the way the multipole moments of a numerical metric
      are read from the asymptotic expansion of the metric functions. We show how one
      should read correctly the first few multipole moments (starting from the
      quadrupole mass moment) and how these corrected moments improve the efficiency of
      describing the metric functions with analytic metrics that have already been used
      in the literature, as well as other consequences of using the correct moments.

PMID- 23003943
TI  - Cosmic microwave background trispectrum and primordial magnetic field limits.
AB  - Primordial magnetic fields will generate non-gaussian signals in the cosmic
      microwave background (CMB) as magnetic stresses and the temperature anisotropy
      they induce depend quadratically on the magnetic field. We compute a new measure
      of magnetic non-gaussianity, the CMB trispectrum, on large angular scales,
      sourced via the Sachs-Wolfe effect. The trispectra induced by magnetic energy
      density and by magnetic scalar anisotropic stress are found to have typical
      magnitudes of approximately a few times 10(-29) and 10(-19), respectively.
      Observational limits on CMB non-gaussianity from WMAP data allow us to
      conservatively set upper limits of a nG, and plausibly sub-nG, on the present
      value of the primordial cosmic magnetic field. This represents the tightest limit
      so far on the strength of primordial magnetic fields, on Mpc scales, and is
      better than limits from the CMB bispectrum and all modes in the CMB power
      spectrum. Thus, the CMB trispectrum is a new and more sensitive probe of
      primordial magnetic fields on large scales.

PMID- 23003944
TI  - Using quasars as standard clocks for measuring cosmological redshift.
AB  - We report hitherto unnoticed patterns in quasar light curves. We characterize
      segments of the quasar's light curves with the slopes of the straight lines fit
      through them. These slopes appear to be directly related to the quasars'
      redshifts. Alternatively, using only global shifts in time and flux, we are able
      to find significant overlaps between the light curves of different pairs of
      quasars by fitting the ratio of their redshifts. We are then able to reliably
      determine the redshift of one quasar from another. This implies that one can use
      quasars as standard clocks, as we explicitly demonstrate by constructing two
      independent methods of finding the redshift of a quasar from its light curve.

PMID- 23003945
TI  - New relations for three-dimensional supersymmetric scattering amplitudes.
AB  - We provide evidence for a duality between color and kinematics in three
      dimensional supersymmetric Chern-Simons matter theories. We show that the six
      point amplitude in the maximally supersymmetric N=8 theory can be arranged so
      that the kinematic factors satisfy the fundamental identity of three-algebras. We
      further show that the four- and six-point N=8 amplitudes can be squared into the
      amplitudes of N=16 three-dimensional supergravity, thus providing evidence for a
      hidden three-algebra structure in the dynamics of the supergravity.

PMID- 23003946
TI  - Quantum electron star.
AB  - We construct and probe a holographic description of a state of matter that
      results from coupling a Fermi liquid to a relativistic conformal field theory
      (CFT). The bulk solution is described by a quantum gas of fermions supported from
      collapse into the gravitational well of anti-de Sitter space by their own
      electrostatic repulsion. A physical interpretation of our result is that, in the
      probe limit studied here, the Landau quasiparticles survive this coupling to a
      CFT.

PMID- 23003949
TI  - Electromagnetic self-energy contribution to M(p)-M(n) and the isovector nucleon
      magnetic polarizability.
AB  - We update the determination of the isovector nucleon electromagnetic self-energy,
      valid to leading order in QED. A technical oversight in the literature concerning
      the elastic contribution to Cottingham's formula is corrected, and modern
      knowledge of the structure functions is used to precisely determine the inelastic
      contribution. We find deltaM(p-n)(gamma) = 1.30(03)(47)   MeV. The largest
      uncertainty arises from a subtraction term required in the dispersive analysis,
      which can be related to the isovector magnetic polarizability. With plausible
      model assumptions, we can combine our calculation with additional input from
      lattice QCD to constrain this polarizability as: beta(p-n) = -0.87(85)*10(-4) 
      fm3.

PMID- 23003950
TI  - Metallodielectric hybrid antennas for ultrastrong enhancement of spontaneous
      emission.
AB  - We devise new optical antennas that reduce the excited-state radiative lifetimes
      of emitters to the order of 100 fs while maintaining quantum efficiencies of
      about 80% at a broadband operation. Here, we combine metallic nanoparticles with
      planar dielectric structures and exploit design strategies from plasmonic
      nanoantennas and concepts from cavity quantum electrodynamics to maximize the
      local density of states and minimize the nonradiative losses incurred by the
      metallic constituents. The proposed metallodielectric hybrid antennas promise an
      important impact on various fundamental and applied research fields, including
      photophysics, ultrafast plasmonics, bright single-photon sources, and Raman
      spectroscopy.

PMID- 23003951
TI  - Imaging polyatomic molecules in three dimensions using molecular frame
      photoelectron angular distributions.
AB  - We demonstrate a method for determining the full three-dimensional molecular
      frame photoelectron angular distribution in polyatomic molecules using methane as
      a prototype. Simultaneous double Auger decay and subsequent dissociation allow
      measurement of the initial momentum vectors of the ionic fragments and the
      photoelectron in coincidence, allowing full orientation by observing a three-ion
      decay pathway, (H+, H+, CH2(+)). We find the striking result that at low
      photoelectron energies the molecule is effectively imaged by the focusing of
      photoelectrons along bond directions.

PMID- 23003948
TI  - Observation of new resonant structures in gammagamma -> omegaphi, phiphi, and
      omegaomega.
AB  - The processes gammagamma -> omegaphi, phiphi, and omegaomega are measured using
      an 870  fb(-1) data sample collected with the Belle detector at the KEKB
      asymmetric-energy e+ e- collider. Production of vector meson pairs is clearly
      observed and their cross sections are measured for masses that range from
      threshold to 4.0 GeV. In addition to signals from well established spin-zero and
      spin-two charmonium states, there are resonant structures below charmonium
      threshold, which have not been previously observed. We report a spin-parity
      analysis for the new structures and determine the products of the eta(c),
      chi(c0), and chi(c2) two-photon decay widths and branching fractions to omegaphi,
      phiphi, and omegaomega.

PMID- 23003952
TI  - Triple Compton effect: a photon splitting into three upon collision with a free
      electron.
AB  - The process in which a photon splits into three after the collision with a free
      electron (triple Compton effect) is the most basic process for the generation of
      a high-energy multiparticle entangled state composed out of elementary quanta.
      The cross section of the process is evaluated in two experimentally realizable
      situations, one employing gamma photons and stationary electrons, and the other
      using keV photons and GeV electrons of an x-ray free electron laser. For the
      first case, our calculation is in agreement with the only available measurement
      of the differential cross section for the process under study. Our estimates
      indicate that the process should be readily measurable also in the second case.
      We quantify the polarization entanglement in the final state by a recently
      proposed multiparticle entanglement measure.

PMID- 23003953
TI  - Size-dependent ultrafast ionization dynamics of nanoscale samples in intense
      femtosecond x-ray free-electron-laser pulses.
AB  - All matter exposed to intense femtosecond x-ray pulses from the Linac Coherent
      Light Source free-electron laser is strongly ionized on time scales competing
      with the inner-shell vacancy lifetimes. We show that for nanoscale objects the
      environment, i.e., nanoparticle size, is an important parameter for the time
      dependent ionization dynamics. The Auger lifetimes of large Ar clusters are found
      to be increased compared to small clusters and isolated atoms, due to
      delocalization of the valence electrons in the x-ray-induced nanoplasma. As a
      consequence, large nanometer-sized samples absorb intense femtosecond x-ray
      pulses less efficiently than small ones.

PMID- 23003954
TI  - Breakdown of the classical description of a local system.
AB  - We provide a straightforward demonstration of a fundamental difference between
      classical and quantum mechanics for a single local system: namely, the absence of
      a joint probability distribution of the position x and momentum p. Elaborating on
      a recently reported criterion by Bednorz and Belzig [Phys. Rev. A 83, 052113
      (2011)] we derive a simple criterion that must be fulfilled for any joint
      probability distribution in classical physics. We demonstrate the violation of
      this criterion using the homodyne measurement of a single photon state, thus
      proving a straightforward signature of the breakdown of a classical description
      of the underlying state. Most importantly, the criterion used does not rely on
      quantum mechanics and can thus be used to demonstrate nonclassicality of systems
      not immediately apparent to exhibit quantum behavior. The criterion is directly
      applicable to any system described by the continuous canonical variables x and p,
      such as a mechanical or an electrical oscillator and a collective spin of a large
      ensemble.

PMID- 23003955
TI  - Phase estimation via quantum interferometry for noisy detectors.
AB  - The sensitivity in optical interferometry is strongly affected by losses during
      the signal propagation or at the detection stage. The optimal quantum states of
      the probing signals in the presence of loss were recently found. However, in many
      cases of practical interest, their associated accuracy is worse than the one
      obtainable without employing quantum resources (e.g., entanglement and squeezing)
      but neglecting the detector's loss. Here, we detail an experiment that can reach
      the latter even in the presence of imperfect detectors: it employs a phase
      sensitive amplification of the signals after the phase sensing, before the
      detection. We experimentally demonstrated the feasibility of a phase estimation
      experiment able to reach its optimal working regime. Since our method uses
      coherent states as input signals, it is a practical technique that can be used
      for high-sensitivity interferometry and, in contrast to the optimal strategies,
      does not require one to have an exact characterization of the loss beforehand.

PMID- 23003956
TI  - Nonequilibrium dynamics of coupled qubit-cavity arrays.
AB  - We study the coherence and fluorescence properties of the coherently pumped and
      dissipative Jaynes-Cummings-Hubbard model describing polaritons in a coupled
      cavity array. At weak hopping we find strong signatures of photon blockade
      similar to single-cavity systems. At strong hopping the state of the photons in
      the array depends on its size. While the photon blockade persists in a dimer
      consisting of two coupled cavities, a coherent state forms on an extended
      lattice, which can be described in terms of a semiclassical model.

PMID- 23003957
TI  - Dissipative rogue waves generated by chaotic pulse bunching in a mode-locked
      laser.
AB  - Rare events of extremely high optical intensity are experimentally recorded at
      the output of a mode-locked fiber laser that operates in a strongly dissipative
      regime of chaotic multiple-pulse generation. The probability distribution of
      these intensity fluctuations, which highly depend on the cavity parameters,
      features a long-tailed distribution. Recorded intensity fluctuations result from
      the ceaseless relative motion and nonlinear interaction of pulses within a
      temporally localized multisoliton phase.

PMID- 23003958
TI  - Twisting light by nonlinear photonic crystals.
AB  - We report the observation of nonlinear interactions in quadratic nonlinear
      crystals having a geometrically twisted susceptibility pattern. The quasi-angular
      momentum of these crystals is imprinted on the interacting photons during the
      nonlinear process so that the total angular momentum is conserved. These crystals
      affect three basic physical quantities of the output photons: energy,
      translational momentum, and angular momentum. Here we study the case of second
      order harmonic vortex beams, generated from a gaussian pump beam. These crystals
      can be used to produce multidimensional entanglement of photons by angular
      momentum states or for shaping the vortex's structure and polarization.

PMID- 23003959
TI  - Delay coupled oscillators for frequency tuning of solid-state terahertz sources.
AB  - We present a solid-state tunable terahertz source that exploits the theory of
      coupled oscillators to simultaneously achieve high output power and frequency
      tuning. Our proposed structure effectively generates and combines high power
      harmonics from multiple synchronized solid-state oscillators in a loop
      configuration. We study the dynamics of the system, find the stable modes, and
      show how the structure can dynamically select a desired coupling mode. Using this
      method, we fabricated 0.29 and 0.32 THz tunable sources with peak output powers
      of 0.76 and 0.5 mW both in a standard 65 nm bulk complementary metal-oxide
      semiconductor technology. This power level is around 10,000 times larger than the
      state of the art which demonstrates that the proposed concept achieves
      significantly higher output power for a given solid-state process.

PMID- 23003960
TI  - Tuning near field radiative heat flux through surface excitations with a metal
      insulator transition.
AB  - The control of heat flow is a formidable challenge due to lack of good thermal
      insulators. Promising new opportunities for heat flow control were recently
      theoretically discovered for radiative heat flow in near field, where large heat
      flow contrasts may be achieved by tuning electronic excitations on surfaces. Here
      we show experimentally that the phase transition of VO2 entails a change of
      surface polariton states that significantly affects radiative heat transfer in
      near field. In all cases the Derjaguin approximation correctly predicted
      radiative heat transfer in near field, but it underestimated the far field limit.
      Our results indicate that heat flow contrasts can be realized in near field that
      can be larger than those obtained in far field.

PMID- 23003961
TI  - Bistability between equatorial and axial dipoles during magnetic field reversals.
AB  - Numerical simulations of the geodynamo in the presence of heterogeneous heating
      are presented. We study the dynamics and the structure of the magnetic field when
      the equatorial symmetry of the flow is broken. If the symmetry breaking is
      sufficiently strong, the m=0 axial dipolar field is replaced by a hemispherical
      magnetic field, dominated by an oscillating m=1 magnetic field. Moreover, for
      moderate symmetry breaking, a bistability between the axial and the equatorial
      dipole is observed. In this bistable regime, the axial magnetic field exhibits
      chaotic switches of its polarity, involving the equatorial dipole during the
      transition period. This new scenario for magnetic field reversals is discussed
      within the framework of Earth's dynamo.

PMID- 23003962
TI  - General cause of sheath instability identified for low collisionality plasmas in
      devices with secondary electron emission.
AB  - A condition for sheath instability due to secondary electron emission (SEE) is
      derived for low collisionality plasmas. When the SEE coefficient of the electrons
      bordering the depleted loss cone in energy space exceeds unity, the sheath
      potential is unstable to a negative perturbation. This result explains three
      different instability phenomena observed in Hall thruster simulations including a
      newly found state with spontaneous ~20  MHz oscillations. When instabilities
      occur, the SEE propagating between the walls becomes the dominant contribution to
      the particle flux, energy loss and axial transport.

PMID- 23003963
TI  - Origin of magnetic stochasticity and transport in plasma microturbulence.
AB  - Nonlinear excitation of linearly stable microtearing modes--with zonal modes
      acting as a catalyst--is shown to be responsible for the near-ubiquitous magnetic
      stochasticity and associated electromagnetic electron heat transport in
      electromagnetic gyrokinetic simulations of plasma microturbulence.

PMID- 23003964
TI  - Few-cycle driven relativistically oscillating plasma mirrors: a source of intense
      isolated attosecond pulses.
AB  - The conditions required for the production of isolated attosecond pulses from
      relativistically oscillating mirrors (ROM) are investigated numerically and
      experimentally. In simulations, carrier-envelope-phase-stabilized three-cycle
      pulses are found to be sufficient to produce isolated attosecond pulses, while
      two-cycle pulses will predominantly lead to isolated attosecond pulses even in
      the absence of carrier-envelope stabilization. Using a state-of-the-art laser
      system delivering three-cycle pulses at multiple-terawatt level, we have
      generated higher harmonics up to 70 eV photon energy via the ROM mechanism. The
      observed spectra are in agreement with theoretical expectations and highlight the
      potential of few-cycle-driven ROM harmonics for intense isolated attosecond pulse
      generation for performing extreme ultraviolet-pump extreme ultraviolet-probe
      experiments.

PMID- 23003965
TI  - Weibel-instability-mediated collisionless shocks in the laboratory with
      ultraintense lasers.
AB  - The formation of nonrelativistic collisionless shocks in the laboratory with
      ultrahigh intensity lasers is studied via ab initio multidimensional particle-in
      cell simulations. The microphysics behind shock formation and dissipation and the
      detailed shock structure are analyzed, illustrating that the Weibel instability
      plays a crucial role in the generation of strong subequipartition magnetic fields
      that isotropize the incoming flow and lead to the formation of a collisionless
      shock, similar to what occurs in astrophysical scenarios. The possibility of
      generating such collisionless shocks in the laboratory opens the way to the
      direct study of the physics associated with astrophysical shocks.

PMID- 23003947
TI  - Strong constraints on the rare decays B(s)(0) -> MU+ MU- and B0 -> MU+ MU-.
AB  - A search for B(s)(0) -> MU+ MU- and B0 -> MU+ MU decays is performed using 1.0 
      fb(-1) of pp collision data collected at sqrt[s] = 7  TeV with the LHCb
      experiment at the Large Hadron Collider. For both decays, the number of observed
      events is consistent with expectation from background and standard model signal
      predictions. Upper limits on the branching fractions are determined to be
      B(B(s)(0) -> MU+ MU-) < 4.5(3.8)*10(-9) and B(B0 -> MU+ MU-) < 1.0(0.81)*10(-9)
      at 95% (90%) confidence level.

PMID- 23003966
TI  - Macroscopic transport of mega-ampere electron currents in aligned carbon-nanotube
      arrays.
AB  - We demonstrate that aligned carbon-nanotube arrays are efficient transporters of
      laser-generated mega-ampere electron currents over distances as large as a
      millimeter. A direct polarimetric measurement of the temporal and the spatial
      evolution of the megagauss magnetic fields (as high as 120 MG) at the target rear
      at an intensity of (10(18)-10(19))  W/cm2 was corroborated by the rear-side hot
      electron spectra. Simulations show that such high magnetic flux densities can
      only be generated by a very well collimated fast electron bunch.

PMID- 23003967
TI  - Synthetic 3D spin-orbit coupling.
AB  - We describe a method for creating a three-dimensional analogue to Rashba spin
      orbit coupling in systems of ultracold atoms. This laser induced coupling uses
      Raman transitions to link four internal atomic states with a tetrahedral
      geometry, and gives rise to a Dirac point that is robust against environmental
      perturbations. We present an exact result showing that such a spin-orbit coupling
      in a fermionic system always gives rise to a molecular bound state.

PMID- 23003968
TI  - Polaron-to-polaron transitions in the radio-frequency spectrum of a quasi-two
      dimensional Fermi gas.
AB  - We measure radio-frequency spectra for a two-component mixture of a 6Li atomic
      Fermi gas in a quasi-two-dimensional regime with the Fermi energy comparable to
      the energy level spacing in the tightly confining potential. Near the Feshbach
      resonance, we find that the observed resonances do not correspond to transitions
      between confinement-induced dimers. The spectral shifts can be fit by assuming
      transitions between noninteracting polaron states in two dimensions.

PMID- 23003969
TI  - Helicity in ropes of chiral nanotubes: calculations and observation.
AB  - Even though isolated defect-free single-wall carbon nanotubes are straight,
      bundles of chiral single-wall carbon nanotubes are often helical according to our
      observations using high-resolution electron microscopy. The driving force for the
      formation of such helices is the energy gain associated with the optimum
      orientational alignment of neighboring nanotubes. Our total energy calculations
      allow us to analyze the torsional and bending stress components in helical
      nanotube ropes and specify under which conditions straight nanotube bundles gain
      energy upon forming a helix.

PMID- 23003970
TI  - van der Waals bonding in layered compounds from advanced density-functional first
      principles calculations.
AB  - Although the precise microscopic knowledge of van der Waals interactions is
      crucial for understanding bonding in weakly bonded layered compounds, very little
      quantitative information on the strength of interlayer interaction in these
      materials is available, either from experiments or simulations. Here, using many
      body perturbation and advanced density-functional theory techniques, we calculate
      the interlayer binding and exfoliation energies for a large number of layered
      compounds and show that, independent of the electronic structure of the material,
      the energies for most systems are around 20  meV/A2. This universality explains
      the successful exfoliation of a wide class of layered materials to produce two
      dimensional systems, and furthers our understanding the properties of layered
      compounds in general.

PMID- 23003971
TI  - Quantum simulation of the cooperative Jahn-Teller transition in 1D ion crystals.
AB  - The Jahn-Teller effect explains distortions and nondegenerate energy levels in
      molecular and solid-state physics via a coupling of effective spins to collective
      bosons. Here we propose and theoretically analyze the quantum simulation of a
      many-body Jahn-Teller model with linear ion crystals subjected to magnetic field
      gradients. We show that the system undergoes a quantum magnetic structural phase
      transition which leads to a reordering of particle positions and the formation of
      a spin-phonon quasicondensate in mesoscopic ion chains.

PMID- 23003972
TI  - Athermal phase separation of self-propelled particles with no alignment.
AB  - We study numerically and analytically a model of self-propelled polar disks on a
      substrate in two dimensions. The particles interact via isotropic repulsive
      forces and are subject to rotational noise, but there is no aligning interaction.
      As a result, the system does not exhibit an ordered state. The isotropic fluid
      phase separates well below close packing and exhibits the large number
      fluctuations and clustering found ubiquitously in active systems. Our work shows
      that this behavior is a generic property of systems that are driven out of
      equilibrium locally, as for instance by self-propulsion.

PMID- 23003973
TI  - Stress-induced variations in the stiffness of micro- and nanocantilever beams.
AB  - The effect of surface stress on the stiffness of cantilever beams remains an
      outstanding problem in the physical sciences. While numerous experimental studies
      report significant stiffness change due to surface stress, theoretical
      predictions are unable to rigorously and quantitatively reconcile these
      observations. In this Letter, we present the first controlled measurements of
      stress-induced change in cantilever stiffness with commensurate theoretical
      quantification. Simultaneous measurements are also performed on equivalent
      clamped-clamped beams. All experimental results are quantitatively and accurately
      predicted using elasticity theory. We also present conclusive experimental
      evidence for invalidity of the long-standing and unphysical axial force model,
      which has been widely applied to interpret measurements using cantilever beams.
      Our findings will be of value in the development of micro- and nanoscale resonant
      mechanical sensors.

PMID- 23003975
TI  - Packing defects into ordered structures: strands on TiO2.
AB  - We have studied vicinal TiO2(110) surfaces by high-resolution scanning tunneling
      microscopy and density functional theory calculations. On TiO2 surfaces
      characterized by a high density of <111> steps, scanning tunneling microscopy
      reveals a high density of oxygen-deficient strandlike adstructures. With the help
      of density functional theory calculations we develop a complete structural model
      for the entire strand and demonstrate these adstructures to be more stable than
      an equivalent amount of bulk defects such as Ti interstitials. We argue that
      strands can form particularly easy on stepped surfaces because building material
      is available at step sites. The strands on TiO2(110) represent point defects that
      are densely packed into ordered adstructures.

PMID- 23003974
TI  - Interfacial effects on nanoconfined diffusive mass transport regimes.
AB  - A hierarchical multiscale modeling approach, incorporating molecular dynamics and
      finite element techniques, is used to study parametrically diffusion regimes
      through nanoconfined fluid. Novel parameters that determine the character of the
      diffusion regime and diffusion kinetics within the nanoscale confined fluids is
      established by exploring diffusion where the interface effects at the solid
      surface are important. New diffusion transport characteristics are established
      when nanochannel confining dimension approaches 3-4 sizes of diffusing molecules,
      which also marks peripheries of the non-fickian transport regime.

PMID- 23003976
TI  - Effect of surface motion on the rotational quadrupole alignment parameter of D2
      reacting on Cu(111).
AB  - Ab initio molecular dynamics (AIMD) calculations using the specific reaction
      parameter approach to density functional theory are presented for the reaction of
      D2 on Cu(111) at high surface temperature (T(s)=925  K). The focus is on the
      dependence of reaction on the alignment of the molecule's angular momentum
      relative to the surface. For the two rovibrational states for which measured
      energy resolved rotational quadrupole alignment parameters are available, and for
      the energies for which statistically accurate rotational quadrupole alignment
      parameters could be computed, statistically significant results of our AIMD
      calculations are that, on average, (i) including the effect of the experimental
      surface temperature (925 K) in the AIMD simulations leads to decreased rotational
      quadrupole alignment parameters, and (ii) including this effect leads to
      increased agreement with experiment.

PMID- 23003977
TI  - Anomalous in-plane electronic scattering in charge ordered Na0.41CoO2.0.6H2O.
AB  - We report electronic transport measurements on high quality floating zone grown
      Na(x)CoO2 and Na0.41CoO2.0.6H2O single crystals. We find an in-plane electronic
      scattering minimum near 11 K and a clear charge ordering at approximately 50 K.
      The electronic and magnetic properties in hydrated and nonhydrated Na0.41CoO2
      samples are similar at higher temperature, but evolve in markedly different ways
      below ~50  K, where a strong ferromagnetic tendency is observed in the hydrated
      sample. Model calculations show the relationship of this tendency to the
      structure of the Fermi surface. The results, particularly the clear differences
      between the hydrated and nonhydrated material show a substantially enhanced
      ferromagnetic tendency upon hydration. Implications for superconductivity are
      discussed.

PMID- 23003978
TI  - Accurate and efficient method for many-body van der Waals interactions.
AB  - An efficient method is developed for the microscopic description of the frequency
      dependent polarizability of finite-gap molecules and solids. This is achieved by
      combining the Tkatchenko-Scheffler van der Waals (vdW) method [Phys. Rev. Lett.
      102, 073005 (2009)] with the self-consistent screening equation of classical
      electrodynamics. This leads to a seamless description of polarization and
      depolarization for the polarizability tensor of molecules and solids. The
      screened long-range many-body vdW energy is obtained from the solution of the
      Schrodinger equation for a system of coupled oscillators. We show that the
      screening and the many-body vdW energy play a significant role even for rather
      small molecules, becoming crucial for an accurate treatment of conformational
      energies for biomolecules and binding of molecular crystals. The computational
      cost of the developed theory is negligible compared to the underlying electronic
      structure calculation.

PMID- 23003979
TI  - Pressure effect on the structural transition and suppression of the high-spin
      state in the triple-layer T'-La4Ni3O8.
AB  - We report a comprehensive high-pressure study on the triple-layer T'-La4Ni3O8
      with a suite of experimental probes, including structure determination, magnetic,
      and transport properties up to 50 GPa. Consistent with a recent ab inito
      calculation, application of hydrostatic pressure suppresses an insulator-metal
      spin-state transition at P(c)~6  GPa. However, a low-spin metallic phase does not
      emerge after the high-spin state is suppressed to the lowest temperature. For
      P>20  GPa, the ambient T' structure transforms gradually to a T(?)-type
      structure, which involves a structural reconstruction from fluorite La-O2-La
      blocks under low pressures to rock-salt LaO-LaO blocks under high pressures.
      Absence of the metallic phase under pressure has been discussed in terms of local
      displacements of O2- ions in the fluorite block under pressure before a global
      T(?) phase is established.

PMID- 23003980
TI  - Spin transistor action from hidden Onsager reciprocity.
AB  - We investigate generic Hamiltonians for confined electrons with weak
      inhomogeneous spin-orbit coupling. Using a local gauge transformation we show how
      the SU(2) Hamiltonian structure reduces to a U(1)*U(1) structure for spinless
      fermions in a fictitious orbital magnetic field, to leading order in the spin
      orbit strength. Using an Onsager relation, we further show how the resulting spin
      conductance vanishes in a two-terminal setup, and how it is turned on by either
      weakly breaking time-reversal symmetry or opening additional transport terminals,
      thus allowing one to switch the generated spin current on or off. We numerically
      check our theory for mesoscopic cavities as well as Aharonov-Bohm rings.

PMID- 23003981
TI  - Strong coupling superconductivity at 8.4 K in an antiperovskite phosphide SrPt3P.
AB  - We report the discovery of a family of ternary platinum phosphides APt3P (A = Ca,
      Sr, and La), which crystallize in an antiperovskite-based structure closely
      related to that of the heavy fermion superconductor CePt3Si. All three phosphides
      showed superconductivity at low temperatures and the highest critical temperature
      T(c) = 8.4  K was observed for SrPt3P. The analysis of specific heat C(T) for
      SrPt3P shows clear evidence for very strong coupling s-wave superconductivity
      with a large ratio between superconducting gap Delta0 and T(c), 2Delta0/k(B)T(c)
      ~ 5, and the presence of low-energy phonons. The presence of multiple Fermi
      surface pockets was inferred from the nonlinear magnetic field dependence of Hall
      resistivity, which we argue might play a role in realizing the strong coupling of
      charge carriers with the low-lying phonons.

PMID- 23003982
TI  - NMR study in the iron-selenide Rb0.74Fe1.6Se2: determination of the
      superconducting phase as iron vacancy-free Rb0.3Fe2Se2.
AB  - 77Se and 87Rb nuclear magnetic resonance (NMR) experiments on Rb0.74Fe1.6Se2
      reveal clearly distinct spectra originating from a majority antiferromagnetic
      (AF) and a minority metallic-superconducting (SC) phase. The very narrow NMR line
      of the SC phase evidences the absence of Fe vacancies and any trace of AF order.
      The Rb content of the SC phase is deduced from intensity measurements identifying
      Rb(0.3(1))Fe2Se2 as the actual composition of the SC fraction. The resulting
      estimate of 0.15  electrons/Fe brings this class of superconductors 245 family
      closer to the other Fe-based superconductor families.

PMID- 23003983
TI  - Electric field control of the magnetic chiralities in ferroaxial multiferroic
      RbFe(MoO4)2.
AB  - The coupling of magnetic chiralities to the ferroelectric polarization in
      multiferroic RbFe(MoO4)2 is investigated by neutron spherical polarimetry.
      Because of the axiality of the crystal structure below T(c)=190   K, helicity and
      triangular chirality are symmetric-exchange coupled, explaining the onset of the
      ferroelectricity in this proper-screw magnetic structure--a mechanism that can be
      generalized to other systems with ferroaxial distortions in the crystal
      structure. With an applied electric field, we demonstrate control of the
      chiralities in both structural domains simultaneously.

PMID- 23003984
TI  - Imaging the first-order magnetic transition in La0.35Pr0.275Ca0.375MnO3.
AB  - The nature of the ferromagnetic, charge, orbital, and antiferromagnetic order in
      La0.35Pr0.275Ca0.375MnO3 on the nano- and microscale was investigated by
      photoemission electron microscopy (PEEM) and resonant elastic soft x-ray
      scattering (RSXS). The structure of the ferromagnetic domains around the Curie
      temperature T(C) indicates that they nucleate under a high degree of lattice
      strain, which is brought about by the charge, orbital, and antiferromagnetic
      order. The combined temperature-dependent PEEM and RSXS measurements suggest that
      the lattice distortions associated with charge and orbital order are glassy in
      nature and that phase separation is driven by the interplay between it and the
      more itinerant charge carriers associated with ferromagnetic metallic order, even
      well below T(C).

PMID- 23003985
TI  - Origin of bulk uniaxial anisotropy in zinc-blende dilute magnetic semiconductors.
AB  - It is demonstrated that the nearest-neighbor Mn pair on the GaAs (001) surface
      has a lower energy for the [110] direction compared to the [110] case. According
      to the group theory and Luttinger's method of invariants, this specific Mn
      distribution results in bulk uniaxial in-plane and out-of-plane anisotropies. The
      sign and magnitude of the corresponding anisotropy energies determined by a
      perturbation method and ab initio computations are consistent with experimental
      results.

PMID- 23003986
TI  - Long-wavelength helimagnetic order and skyrmion lattice phase in Cu2OSeO3.
AB  - We report a long-wavelength helimagnetic superstructure in bulk samples of the
      ferrimagnetic insulator Cu2OSeO3. The magnetic phase diagram associated with the
      helimagnetic modulation inferred from small-angle neutron scattering and
      magnetization measurements includes a skyrmion lattice phase and is strongly
      reminiscent of MnSi, FeGe, and Fe(1-x)Co(x)Si, i.e., binary isostructural
      siblings of Cu2OSeO3 that order helimagnetically. The temperature dependence of
      the specific heat of Cu2OSeO3 is characteristic of nearly critical spin
      fluctuations at the helimagnetic transition. This provides putative evidence for
      effective spin currents as the origin of enhancements of the magnetodielectric
      response instead of atomic displacements considered so far.

PMID- 23003987
TI  - Theory of Raman scattering in one-dimensional quantum spin-1/2 antiferromagnets.
AB  - We study theoretically the Raman-scattering spectra in the one-dimensional (1D)
      quantum spin-1/2 antiferromagnets. The analysis reveals that their low-energy
      dynamics is exquisitely sensitive to various perturbations to the Heisenberg
      chain with nearest-neighbor exchange interactions, such as magnetic anisotropy,
      longer-range exchange interactions, and bond dimerization. These weak
      interactions are mainly responsible for the Raman scattering and give rise to
      different types of spectra as functions of frequency, temperature, and external
      field. In contrast to the Raman spectra in higher dimensions in which the two
      magnon process is dominant, those in 1D antiferromagnets provide much richer
      information on these perturbations.

PMID- 23003988
TI  - Electronic ferroelectricity in a molecular crystal with large polarization
      directing antiparallel to ionic displacement.
AB  - Ferroelectric polarization of 6.3  MUC cm(-2) is induced by the neutral-to-ionic
      transition, upon which nonpolar molecules of electron donor tetrathiafulvalene
      (TTF) and acceptor p-chloranil (CA) are incompletely ionized to +/-0.60e and
      dimerized along the molecular stacking chain. We find that the ferroelectric
      properties are governed by intermolecular charge transfer rather than simple
      displacement of static point charge on molecules. The observed polarization and
      poling effect on the absolute structural configuration can be interpreted in
      terms of electronic ferroelectricity, which not only exhibits antiparallel
      polarity to the ionic displacement but also enhances the polarization more than
      20 times that of the point-charge model.

PMID- 23003989
TI  - Field emission of electrons generated by the near field of strongly coupled
      plasmons.
AB  - Field emission of electrons is generated solely by the ultrastrong near-field of
      strongly coupled plasmons without the help of a noticeable dc field. Strongly
      coupled plasmons are excited at Au nanoparticles in subnanometer distance to a Au
      film by femtosecond laser pulses. Field-emitted electrons from individual
      nanoparticles are detected by means of photoelectron emission microscopy and
      spectroscopy. The dependence of total electron yield and kinetic energy on the
      laser power proves that field emission is the underlying emission process. We
      derive a dynamic version of the Fowler-Nordheim equation that yields perfect
      agreement with the experiment.

PMID- 23003990
TI  - Spatial structures and giant number fluctuations in models of active matter.
AB  - The large scale fluctuations of the ordered state in active matter systems are
      usually characterized by studying the "giant number fluctuations" of particles in
      any finite volume, as compared to the expectations from the central limit
      theorem. However, in ordering systems, the fluctuations in density ordering are
      often captured through their structure functions deviating from Porod's law. In
      this Letter we study the relationship between giant number fluctuations and
      structure functions for different models of active matter as well as other
      nonequilibrium systems. A unified picture emerges, with different models falling
      in four distinct classes depending on the nature of their structure functions.
      For one class, we show that experimentalists may find Porod's law violation, by
      measuring subleading corrections to the number fluctuations.

PMID- 23003991
TI  - Scaling laws for the slip velocity in dense granular flows.
AB  - In this Letter, the two-dimensional dense flow of polygonal particles on an
      incline with a flat frictional inferior boundary is analyzed by means of contact
      dynamics discrete element simulations, in order to develop boundary conditions
      for continuum models of dense granular flows. We show the evidence that the
      global slip phenomenon deviates significantly from simple sliding: a finite slip
      velocity is generally found for shear forces lower than the sliding threshold for
      particle-wall contacts. We determined simple scaling laws for the dependence of
      the slip velocity on shear rate, normal and shear stresses, and material
      parameters. The importance of a correct determination of the slip at the base of
      the incline, which is crucial for the calculation of flow rates, is discussed in
      relation to natural flows.

PMID- 23003992
TI  - Photoelectron dynamics in x-ray free-electron-laser diffractive imaging of
      biological samples.
AB  - X-ray free electron lasers hold the promise of enabling atomic-resolution
      diffractive imaging of single biological molecules. We develop a hybrid continuum
      particle model to describe the x-ray induced damage and find that the
      photoelectron dynamics and electrostatic confinement strongly affect the time
      scale of the damage processes. These phenomena are not fully captured in
      hydrodynamic modeling approaches.

PMID- 23003993
TI  - Surface hydration amplifies single-well protein atom diffusion propagating into
      the macromolecular core.
AB  - The effect of surface hydration water on internal protein motion is of
      fundamental interest in molecular biophysics. Here, by decomposing the picosecond
      to nanosecond atomic motion in molecular dynamics simulations of lysozyme at
      different hydration levels into three components--localized single-well
      diffusion, methyl group rotation, and nonmethyl jumps--we show that the effect of
      surface hydration is mainly to increase the volume of the localized single-well
      diffusion. These diffusive motions are coupled in such a way that the hydration
      effect propagates from the protein surface into the dry core.

PMID- 23003994
TI  - Cholesterol mediates membrane curvature during fusion events.
AB  - Biomembranes undergo extensive shape changes as they perform vital cellular
      functions. The mechanisms by which lipids and proteins control membrane curvature
      remain unclear. We use x-ray reflectivity, grazing incidence x-ray diffraction,
      and epifluorescence microscopy to study binding of HIV-1 glycoprotein gp41's
      membrane-bending domain to DPPC/cholesterol monolayers of various compositions at
      the air-liquid interface. The results offer a new insight into how membrane
      curvature could be regulated by cholesterol during fusion of the viral lipid
      envelope and the host cell membranes.

PMID- 23003995
TI  - Thermal, autonomous replicator made from transfer RNA.
AB  - Evolving systems rely on the storage and replication of genetic information. Here
      we present an autonomous, purely thermally driven replication mechanism. A pool
      of hairpin molecules, derived from transfer RNA replicates the succession of a
      two-letter code. Energy is first stored thermally in metastable hairpins.
      Thereafter, energy is released by a highly specific and exponential replication
      with a duplication time of 30 s, which is much faster than the tendency to
      produce false positives in the absence of template. Our experiments propose a
      physical rather than a chemical scenario for the autonomous replication of
      protein encoding information in a disequilibrium setting.

PMID- 23003996
TI  - Universal protein fluctuations in populations of microorganisms.
AB  - The copy number of any protein fluctuates among cells in a population;
      characterizing and understanding these fluctuations is a fundamental problem in
      biophysics. We show here that protein distributions measured under a broad range
      of biological realizations collapse to a single non-gaussian curve under scaling
      by the first two moments. Moreover, in all experiments the variance is found to
      depend quadratically on the mean, showing that a single degree of freedom
      determines the entire distribution. Our results imply that protein fluctuations
      do not reflect any specific molecular or cellular mechanism, and suggest that
      some buffering process masks these details and induces universality.

PMID- 23003997
TI  - Emergence of spontaneous twist and curvature in non-euclidean rods: application
      to Erodium plant cells.
AB  - We present a limiting model for thin non-euclidean elastic rods. Originating from
      the three-dimensional (3D) reference metric of the rod, which is determined by
      its internal material structure, we derive a 1D reduced rod theory. Specifically,
      we show how the spontaneous twist and curvature of a rod emerge from the
      reference metric derivatives. Thus, the model allows calculating the
      unconstrained equilibrium configuration of a thin rod directly from its internal
      structure. The model is applied to the study of cells from members of the
      Geraniaceae plant family and their configurational response to dehydration. We
      show how the geometrical arrangement of cellulose fibrils on the cell walls
      determines the helical shapes of isolated cells.

PMID- 23003999
TI  - Fluctuations in symmetric diblock copolymers: testing theories old and new.
AB  - Computer simulations are used to study composition fluctuations in disordered
      diblock copolymer melts over a range of values of the chain length N, and test
      several theories for the structure factor S(q). Specifically, we test the random
      phase approximation (RPA), which is based on a self-consistent field treatment of
      fluctuations, the Fredrickson-Helfand theory, which was designed to describe
      fluctuations near the order-disorder transition, and the relatively new
      renormalized one-loop (ROL) theory. The results confirm claims that the RPA is
      exact in the limit N->infinity and that the ROL theory yields the dominant
      corrections to the RPA within a systematic expansion in powers of N(-1/2), and
      show that the ROL theory is much more accurate than either older theory.

PMID- 23003998
TI  - Contractile units in disordered actomyosin bundles arise from F-actin buckling.
AB  - Bundles of filaments and motors are central to contractility in cells. The
      classic example is striated muscle, where actomyosin contractility is mediated by
      highly organized sarcomeres which act as fundamental contractile units. However,
      many contractile bundles in vivo and in vitro lack sarcomeric organization. Here
      we propose a model for how contractility can arise in bundles without sarcomeric
      organization and validate its predictions with experiments on a reconstituted
      system. In the model, internal stresses in frustrated arrangements of motors with
      diverse velocities cause filaments to buckle, leading to overall shortening. We
      describe the onset of buckling in the presence of stochastic motor head
      detachment and predict that buckling-induced contraction occurs in an
      intermediate range of motor densities. We then calculate the size of the
      "contractile units" associated with this process. Consistent with these results,
      our reconstituted actomyosin bundles show contraction at relatively high motor
      density, and we observe buckling at the predicted length scale.

PMID- 23004000
TI  - Hydrodynamic-driven stability analysis of morphological patterns on stalactites
      and implications for cave paleoflow reconstructions.
AB  - A novel hydrodynamic-driven stability analysis is presented for surface patterns
      on speleothems, i.e., secondary sedimentary cave deposits, by coupling fluid
      dynamics to the geochemistry of calcite precipitation or dissolution. Falling
      film theory provides the solution for the flow-field and depth perturbations, the
      latter being crucial to triggering patterns known as crenulations. In a wide
      range of Reynolds numbers, the model provides the dominant wavelengths and
      pattern celerities, in fair agreement with field data. The analysis of the phase
      velocity of ridges on speleothems has a potential as a proxy of past film flow
      rates, thus suggesting a new support for paleoclimate analyses.

PMID- 23004001
TI  - Comment on "New structural picture of the Ge2Sb2Te5 phase-change alloy".

PMID- 23004003
TI  - Comment on "New structural picture of the Ge2Sb2Te5 phase-change alloy".

PMID- 23004004
TI  - Engineering islets for improved performance by optimized reaggregation in a
      micromold.
AB  - Isolated islets can provide a source of tissue for research, transplantation, and
      drug discovery to develop therapies for diabetes. Empirical modeling of islet
      diffusion barriers demonstrated that only the outermost layers of cells were
      exposed to glucose and sufficient oxygen levels, resulting in core cell death.
      Islets under a diameter of 100 MUm exhibited a lower diffusion barrier, superior
      survival rates, and improved functional properties. Utilizing these observations,
      we engineered optimal islets by dispersing them into single cells and
      reaggregating them over several days in a micromold. These custom-designed
      micromolds contained conical-shaped recesses that enhanced reaggregation of cells
      into a defined geometry. The engineered islets, or Kanslets, were all under 100
      MUm in diameter, and had the same general cellular composition as native islets.
      Kanslets continued to produce new insulin molecules and had microvilli on the
      islet surface, much like native islets. The engineered islets had a statistically
      higher viability (percent of live cells), and increased glucose diffusion
      compared to native islets. In addition, they remained responsive to varying
      glucose levels by secreting insulin. When transplanted into diabetic rats,
      engineered islets performed reduced random blood glucose to normal levels within
      48 h. Optimally, engineering islets may be a suitable alternative to utilizing
      native, isolated islet tissue for a variety of applications. Reaggregating tissue
      in an optimized manner using our engineered micromold approach has immense impact
      for three-dimensional tissue production and its subsequent use in research, drug
      discovery, and the clinic.

PMID- 23004005
TI  - Peironimev-Plus(r) in the treatment of chronic inflammation of tunica albuginea
      (Peyronie's disease). results of a controlled study.
AB  - Peyronie's Disease (PD) is a connective tissue disorder involving the growth of
      fibrous plaques in penile corpora cavernosa (tunica albuginea). The conservative
      treatment is indicated in the development stage of PD for at least one year after
      diagnosis and in case of penile pain. This study was conducted to demonstrate the
      possible effectiveness of the new substances of Peironimev-plus(r). Sixty four
      patients (age: 29-65 years, mean: 52.57 +/- 9.06) diagnosed with PD were enrolled
      in a medical treatment. All patients underwent the following diagnostic tests:
      penile ultrasound, photographic documentation of penile curvature, IIEF
      questionnaire (erectile function score), pain evaluation with Visual Analogue
      pain Scale (VAS). The patients were divided into two treatment groups with
      different combinations of drugs: A = Peironimev-plus/oral/one tablet-daily +
      Verapamil injection (peri-lesional) 10 mg/every two weeks + Verapamil
      iontophoresis/5 mg/three times a week - for 6 months; B = Verapamil injection
      (peri-lesional) 10 mg/every two weeks + Verapamil iontophoresis/5 mg/three times
      a week - for 6 months. Intergroup analysis revealed statistically significant
      differences: in group A the effective plaque size reduction was -30.8% while in
      the group B the reduction was -18.0% (p=0.000). In group A the improvement of
      curvature occurred in 85.1% of the cases while in group B this occurred only in
      53.5% (p=0.024), moreover the mean curvature decrease was respectively - 8.7
      degrees  and - 4.6 degrees  (p=0.002). IIEF score was significantly improved in
      group A patients with erectile dysfunction (p=0.02). Our results suggest that
      Peironimev-plus is an effective drug in treating PD and it may help to prevent
      the progression of PD.

PMID- 23004006
TI  - Chronic spontaneous urticaria: epidemiological characteristics focusing on the
      histocompatibility profile and presence of antibodies.
AB  - BACKGROUND: Understanding the etiopathogenesis of chronic spontaneous urticaria
      (CSU) remains a challenge. The clinical and laboratory characteristics relating
      to its histocompatibility profile and autoimmunity are constant research topics.
      OBJECTIVES: To analyze the clinical and laboratory characteristics of patients
      with CSU by means of a cross-sectional study, focusing on the histocompatibility
      profile, presence of antinuclear antibodies (ANA) and presence of
      antithyroperoxidase antibodies (anti-TPO). MATERIALS & METHODS: Sixty-seven
      adults with CSU were analyzed. The autologous serum skin test (ASST), ANA and
      anti-TPO were performed in all cases and MHC classes I and II (loci A, B and DR)
      were evaluated in 49 patients. RESULTS: The factors that worsened urticaria
      included use of non-steroid anti-inflammatory drugs, emotional stress and
      physical stimuli, reported by 27%, 16% and 15% of these patients, respectively.
      The ASST test was positive in 49 patients (73%) and anti-TPO and ANA were present
      in 15 (22.4%) and 7 (10.5%), respectively. The OR (with 95% CI) for the
      association between ANA and anti-TPO was 5.94 (1.16-30.42), and thus
      statistically significant. There was a favorable association (with statistical
      significance) between HLA B*50 and patients with CSU, with OR (95% CI) of 2.96
      (1.17- 7.48). CONCLUSION: A significant favorable association was found between
      these patients and HLA B*50, and between the presence of anti-TPO and ANA. The
      greater prevalence of HLA B*50 in these patients and the association between ANA
      and anti-TPO reinforce the possibility that an immunogenic mechanism may be the
      triggering factor for CSU.

PMID- 23004008
TI  - Health-related quality of life of patients with severe heart failure. A cross
      sectional multicentre study.
AB  - BACKGROUND: Heart failure is a serious chronic syndrome that is accompanied by
      significant physical and psychological burdens, resulting in poor quality of
      life. AIM: To assess the quality of life of patients with severe heart failure
      and its correlation with patient demographic, socio-economic and clinical
      characteristics. METHOD: We studied 199 patients with heart failure who were
      hospitalized in the Cardiology Department of three general hospitals of Greece
      during a 1-year period. Demographic and socio-economic data were obtained using a
      short questionnaire, while clinical data were obtained from medical record
      review. The assessment of the patients' quality of life was performed using
      Minnesota Life with Heart Failure Questionnaire (MLWHFQ). FINDINGS: The mean
      MLWHFQ score was 62.7 (+/-20.3). Significantly lower quality of life was found in
      patients with diabetes mellitus (Coefficient beta (beta)=11.4; 95% Confidence
      Interval (CI), 5.2-17.5), hypertension (beta=10.3; CI, 1.4-19.1), chronic renal
      failure (beta=13.9; CI, 5.9-21.9), chronic respiratory failure (beta=11.2; CI,
      4.7-17.7), cancer (beta=12.3; CI, 2.3-22.4), psychiatric disease (beta=10.5; CI,
      0.6-20.4) and those patients who were classified in New York Heart Association
      class IV (beta=10.6, CI=4.1-17.0). CONCLUSIONS: The average score of the MLWHFQ
      was high, and this reflects the poor quality of life of patients. Higher scores
      in specific patient groups show the negative influence of these factors in
      quality of life. The holistic care of patients with heart failure by a
      multidisciplinary team of healthcare professionals could improve their quality of
      life.

PMID- 23004009
TI  - Dinoprostone vaginal pessary for induction of labour: safety of use for up to 24
      h.
AB  - BACKGROUND: Cervidil((r)) (dinoprostone) intravaginal pessaries are used for
      induction of labour and maintain serum prostaglandin levels for up to 24 h. The
      Therapeutic Goods Administration approves Cervidil((r)) for 12-h use. However,
      twenty-four-hour use of Cervidil((r)) is supported in Europe, New Zealand,
      America and some Australian hospitals. AIM: To assess the safety of Cervidil((r))
      use for up to 24 h for induction of labour in nulliparous women. METHODS: A
      retrospective cohort study of 269 consecutive women receiving Cervidil((r)) at
      the Royal Brisbane and Women's Hospital (RBWH) between July 2007 and December
      2008 was performed. The primary outcome measures were frequency of, and time to,
      uterine tachysystole with or without fetal heart rate (FHR) changes. Secondary
      outcome measures included frequency of maternal (intrapartum temperature,
      postpartum haemorrhage) and neonatal (low Apgars, resuscitation, nursery
      admission) morbidity. Morbidity outcomes of those who received Cervidil((r)) for
      less than or equal to 12 h were compared with those who received Cervidil((r))
      for more than 12 h. RESULTS: Uterine tachysystole occurred in 9.3% of patients
      receiving Cervidil((r)) , with a mean time to tachysystole of 10 h. The majority
      of cases (68%) occurred within 12 h of use. There was no increase in maternal or
      neonatal morbidity for those who received Cervidil((r)) for longer than 12 h.
      CONCLUSION: Twenty-four-hour use of Cervidil((r)) is likely as safe as 12-h use
      for induction of labour in nulliparous women.

PMID- 23004010
TI  - Sustainable occupational responses to climate change through lifestyle choices.
AB  - Abstract   Occupational therapists and occupational scientists are increasingly
      aware of the relationship between occupation and global climate change, with some
      working to raise awareness of the issues and others proposing that an
      occupational perspective can make a valuable contribution to understanding and
      addressing the issues. In this discussion paper the United Nations Global Survey
      on Sustainable Lifestyles ( 1 ), which reports young adults' beliefs about
      everyday occupations that have a substantial impact on the environment (food,
      housekeeping, and transportation) is introduced. The authors argue that the
      survey findings are a valuable resource for occupational therapists who are
      concerned about global climate change and work with young adults (age 18-35),
      providing valuable insights into their concerns and preferences in relation to
      sustainability. To illustrate the insights contained in the reports, findings
      from four countries are presented: New Zealand and Sweden, the authors' countries
      of origin, and the Philippines and Lebanon which have people living in New
      Zealand and Sweden. Application to individual and community-based interventions
      to promote more sustainable lifestyles is suggested, along with studies to
      examine the perspectives of young adults with a disability, as their concerns and
      sustainability preferences might differ due to the barriers that limit their
      participation in educational and vocational occupations.

PMID- 23004011
TI  - A highly compliant protein native state with a spontaneous-like mechanical
      unfolding pathway.
AB  - The mechanical properties of proteins and their force-induced structural changes
      play key roles in many biological processes. Previous studies have shown that
      natively folded proteins are brittle under tension, unfolding after small
      mechanical deformations, while partially folded intermediate states, such as
      molten globules, are compliant and can deform elastically a great amount before
      crossing the transition state barrier. Moreover, under tension proteins appear to
      unfold through a different sequence of events than during spontaneous unfolding.
      Here, we describe the response to force of the four-alpha-helix acyl-CoA binding
      protein (ACBP) in the low-force regime using optical tweezers and ratcheted
      molecular dynamics simulations. The results of our studies reveal an
      unprecedented mechanical behavior of a natively folded protein. ACBP displays an
      atypical compliance along two nearly orthogonal pulling axes, with transition
      states located almost halfway between the unfolded and folded states.
      Surprisingly, the deformability of ACBP is greater than that observed for the
      highly pliant molten globule intermediate states. Furthermore, when manipulated
      from the N- and C-termini, ACBP unfolds by populating a transition state that
      resembles that observed during chemical denaturation, both for structure and
      position along the reaction coordinate. Our data provide the first experimental
      evidence of a spontaneous-like mechanical unfolding pathway of a protein. The
      mechanical behavior of ACBP is discussed in terms of topology and helix
      propensity.

PMID- 23004012
TI  - Graftula: a composite access consisting of a graft used to repair a dysfunctional
      hemodialysis fistula.
AB  - Nonmaturing or dysfunctional hemodialysis fistulas are often repaired with
      interposition grafts placed either within the fistula (fistula-to-fistula
      configuration), or connected to another vein (fistula-to-vein configuration). The
      goal of this study was to compare the survival and usefulness of the composite
      accesses thus created, which we call "graftulas," with upperarm grafts. This was
      a retrospective study wherein we determined the survival and thrombosis rates of
      graftulas (n=24) and upper arm grafts (n=31) placed 1/1/07 through 12/31/09 and
      followed through 11/30/10. Graftulas resembled grafts as most (96%) were
      successfully cannulated in 65 +/- 43 days. Survival of graftulas was also similar
      to grafts (58%, 47%, and 32% vs. 56%, 47%, and 39% at 1, 2, and 3 years
      respectively, p=0.60). However, graftulas had a lower thrombosis rate than grafts
      (0.5 vs. 1.2 per patient year, p=0.04), and in the fistula-to-fistula
      configuration, a 2-year thrombosis-free survival of 78%. Total survival of the
      access site (fistula+graftula) was 92%, 73%, and 42% at 1, 3, and 5 years,
      respectively. Graftulas possess certain beneficial properties of fistulas and
      grafts that allows for continued use of the original access site.

PMID- 23004013
TI  - Neurosurgical input at pre-natal counselling for parents of babies with Spina
      bifida.
AB  - Prenatal counselling can be helpful to parents in making a decision with regard
      to continuation of the pregnancy or to help prepare for the birth and the future
      life of a child with Spina bifida. We aimed to assess the effectiveness of our
      specialist neuro counselling sessions and to highlight areas that could be
      improved upon. This was in the form of a questionnaire given to parents, who had
      been through the counselling and continued with their pregnancy. The areas
      highlighted for improvement were more explicit information about urinary
      catheterisation, the need for admission to the special care baby unit (SCBU) and
      the need for an information leaflet on Spina bifida.

PMID- 23004014
TI  - Habitat complexity does not promote coexistence in a size-structured intraguild
      predation system.
AB  - Size-dependent interactions and habitat complexity have been identified as
      important factors affecting the persistence of intraguild predation (IGP)
      systems. Habitat complexity has been suggested to promote intraguild (IG) prey
      and intraguild predator coexistence through weakening trophic interactions
      particularly the predation link. Here, we experimentally investigate the effects
      of habitat complexity on coexistence and invasion success of differently sized IG
      predators in a size-structured IGP system consisting of the IG-predator Poecilia
      reticulata and a resident Heterandria formosa IG-prey population. The experiments
      included medium-long and long-term invasion experiments, predator-prey
      experiments and competition experiments to elucidate the mechanisms underlying
      the effect of prey refuges. Habitat complexity did not promote the coexistence of
      IG-predator and IG-prey, although the predation link was substantially weakened.
      However, the presence of habitat structure affected the invasion success of large
      IG-predators negatively and the invasion success of small IG-predators
      positively. The effect of refuges on size-dependent invasion success could be
      related to a major decrease in the IG-predator's capture rate and a shift in the
      size distribution of IG-predator juveniles. In summary, habitat complexity had
      two main effects: (i) the predation link was diminished, resulting in a more
      competition driven system and (ii) the overall competitive abilities of the two
      species were equalized, but coexistence was not promoted. Our results suggest
      that in a size-structured IGP system, individual level mechanisms may gain in
      importance over species level mechanisms in the presence of habitat complexity.

PMID- 23004015
TI  - Why there is a wide difference in the clinical and mycological results in
      different onychomycosis clinical studies.

PMID- 23004016
TI  - Environmental and centrifugal factors influencing the visco-elastic properties of
      oral biofilms in vitro.
AB  - Centrifugal compaction causes changes in the surface properties of bacterial
      cells. It has been shown previously that the surface properties of planktonic
      cells change with increasing centrifugal compaction. This study aimed to analyze
      the influences of centrifugal compaction and environmental conditions on the
      visco-elastic properties of oral biofilms. Biofilms were grown out of a layer of
      initially adhering streptococci, actinomyces or a combination of these. Different
      uni-axial deformations were induced on the biofilms and the load relaxations were
      measured over time. Linear-Regression-Analysis demonstrated that both the
      centrifugation coefficient for streptococci and induced deformation influenced
      the percentage relaxation. Centrifugal compaction significantly influenced
      relaxation only upon compression of the outermost 20% of the biofilm (p < 0.05),
      whereas biofilm composition became influential when 50% deformation was induced,
      invoking re-arrangement of the bacteria in deeper biofilm structures. In summary,
      the effects of centrifugal compaction of initially adhering, centrifuged bacteria
      extend to the visco-elastic properties of biofilms, indicating that the initial
      bacterial layer influences the structure of the entire biofilm.

PMID- 23004017
TI  - Effect of bacterial biofilms formed on fouling-release coatings from natural
      seawater and Cobetia marina, on the adhesion of two marine algae.
AB  - Previous studies have shown that bacterial biofilms formed from natural seawater
      (NSW) enhance the settlement of spores of the green alga Ulva linza, while single
      species biofilms may enhance or reduce settlement, or have no effect at all.
      However, the effect of biofilms on the adhesion strength of algae, and how that
      may be influenced by coating/surface properties, is not known. In this study, the
      effect of biofilms formed from natural seawater and the marine bacterium Cobetia
      marina, on the settlement and the adhesion strength of spores and sporelings of
      the macroalga U. linza and the diatom Navicula incerta, was evaluated on
      Intersleek((r)) 700, Intersleek((r)) 900, poly(dimethylsiloxane) and glass. The
      settlement and adhesion strength of these algae were strongly influenced by
      biofilms and their nature. Biofilms formed from NSW enhanced the settlement
      (attachment) of both algae on all the surfaces while the effect of biofilms
      formed from C. marina varied with the coating type. The adhesion strength of
      spores and sporelings of U. linza and diatoms was reduced on all the surfaces
      biofilmed with C. marina, while adhesion strength on biofilms formed from NSW was
      dependent on the alga (and on its stage of development in the case of U. linza),
      and coating type. The results illustrate the complexity of the relationships
      between fouling algae and bacterial biofilms and suggest the need for caution to
      avoid over-generalisation.

PMID- 23004018
TI  - Effect of adsorbed fibronectin on the differential adhesion of osteoblast-like
      cells and Staphylococcus aureus with and without fibronectin-binding proteins.
AB  - The influence of fibronectin (Fn) coated surfaces patterned with poly(ethylene
      glycol) microgels having inter-gel spacings between 0.5 and 3.0 MUm on the
      adhesion of Staphylococcus aureus strains with and without Fn-binding proteins
      and cellular adhesion/spreading was investigated. Quantitative force measurements
      between a S. aureus cell and a patterned surface showed that the adhesion force
      between the bacterium and the patterned surface increased substantially after Fn
      adsorption, regardless of the strain used, but decreased with decreasing inter
      gel spacing. In flow-chamber experiments, the Fn-binding strain adhered at a
      higher rate after Fn adsorption than the strain lacking Fn-binding proteins. In
      both cases, the adhesion rates decreased with decreasing inter-gel spacing.
      Osteoblast-like cells could bind to patterned surfaces despite the microgels, and
      adsorbed Fn substantially amplified this effect. Even under highly non-adhesive
      conditions associated with closely spaced microgels, adsorbed Fn preserves a
      window of inter-gel spacing around 1 MUm where the adhesion of staphylococcal
      cells is hindered while cells can still adhere and spread.

PMID- 23004019
TI  - A novel approach combining the Calgary Biofilm Device and Phenotype MicroArray
      for the characterization of the chemical sensitivity of bacterial biofilms.
AB  - A rapid method for screening the metabolic susceptibility of biofilms to toxic
      compounds was developed by combining the Calgary Biofilm Device (MBEC device) and
      Phenotype MicroArray (PM) technology. The method was developed using Pseudomonas
      alcaliphila 34, a Cr(VI)-hyper-resistant bacterium, as the test organism. P.
      alcaliphila produced a robust biofilm after incubation for 16 h, reaching the
      maximum value after incubation for 24 h (9.4 * 10(6) +/- 3.3 * 10(6) CFU peg(
      1)). In order to detect the metabolic activity of cells in the biofilm, dye E
      (5*) and menadione sodium bisulphate (100 MUM) were selected for redox detection
      chemistry, because they produced a high colorimetric yield in response to
      bacterial metabolism (340.4 +/- 6.9 Omnilog Arbitrary Units). This combined
      approach, which avoids the limitations of traditional plate counts, was validated
      by testing the susceptibility of P. alcaliphila biofilm to 22 toxic compounds.
      For each compound the concentration level that significantly lowered the
      metabolic activity of the biofilm was identified. Chemical sensitivity analysis
      of the planktonic culture was also performed, allowing comparison of the
      metabolic susceptibility patterns of biofilm and planktonic cultures.

PMID- 23004020
TI  - Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8
      monoclonal antibody.
AB  - Gangliosides are glycosphingolipids found on the cell surface. They act as
      recognition molecules or signal modulators and regulate cell proliferation and
      differentiation. N-glycolylneuraminic acid (NeuGc)-containing gangliosides have
      been detected in some neoplasms in humans, although they are usually absent in
      normal human tissues. Our aim was to evaluate the presence of NeuGc-containing
      gangliosides including GM3 (NeuGc) and assess their relationship with the
      prognosis of non-small-cell lung cancer (NSCLC). NeuGc-containing ganglioside
      expression in NSCLC tissues was analyzed immunohistochemically using the mouse
      monoclonal antibody GMR8, which is specific for gangliosides with NeuGc alpha
      2,3Gal-terminal structures. On the basis of NeuGc-containing ganglioside
      expression, we performed survival analysis. We also investigated the differences
      in the effects of GM3 (N-acetylneuraminic acid [NeuAc]) and GM3 (NeuGc) on
      inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase in A431
      cells. As a result, the presence of NeuGc-containing gangliosides was evident in
      86 of 93 (93.5%) NSCLC samples. The NSCLC patients with high NeuGc-containing
      ganglioside expression had a low overall survival rate and a significantly low
      progression-free survival rate. In the in vitro study, the inhibitory effect of
      GM3 on EGFR tyrosine kinase in A431 cells after exposure to GM3 (NeuGc) was lower
      than that after exposure to GM3 (NeuAc). In conclusion, NeuGc-containing
      gangliosides including GM3 (NeuGc) are widely expressed in NSCLC, and NeuGc
      containing ganglioside expression is associated with patient survival. The
      difference in the effects of GM3 (NeuGc) and GM3 (NeuAc) on the inhibition of
      EGFR tyrosine kinase might contribute to improvement in the prognosis of NSCLC
      patients.

PMID- 23004021
TI  - Metallic Yb2AuGe3: an ordered superstructure in the AlB2-type family with mixed
      valent Yb and a high-temperature phase transition.
AB  - The intermetallic compound Yb(2)AuGe(3) was synthesized from indium flux.
      Yb(2)AuGe(3) crystallizes in the orthorhombic Ca(2)AgSi(3)-type structure which
      is an ordered superstructure of the AlB(2) structure type. The structure was
      refined in the Fmmm space group with lattice parameters a = 8.5124(17) A, b =
      14.730(3) A, c = 8.4995(17) A. Temperature-dependent powder X-ray diffraction
      studies show that Yb(2)AuGe(3) undergoes a phase transition from orthorhombic to
      hexagonal upon heating above 773 K. The compound shows weak paramagnetism that
      derives from a combination of Curie and Pauli paramagnetism with a magnetic
      moment value of 0.33(2) MU(B)/Yb atom. Magnetic ordering was not observed down to
      2 K.  Yb(2)AuGe(3) is metallic, and at low temperature the resistivity varies as
      T(2), indicating possible Fermi liquid behavior. Heat capacity measurements
      suggest that Yb(2)AuGe(3) is possibly a moderate heavy fermion system.

PMID- 23004022
TI  - Improving the comprehensiveness and sensitivity of sheathless capillary
      electrophoresis-tandem mass spectrometry for proteomic analysis.
AB  - We describe a solid phase microextraction (SPME), multistep elution, transient
      isotachophoresis (tITP) capillary electrophoresis-tandem mass spectrometry (CE
      MS/MS) procedure which employs a high sensitivity porous electrospray ionization
      (ESI) sprayer for the proteomic analysis of a moderately complex protein mixture.
      In order to improve comprehensiveness and sensitivity over a previously reported
      proteomic application of the ESI sprayer, we evaluated preconcentration with SPME
      and multistep elution prior to tITP stacking and CE separation. To maximize
      separation efficiency, we primarily employed electrokinetic methods for elution
      and separation after loading the sample by application of pressure. Conditions
      were developed for optimum simultaneous electrokinetic elution and sample
      stacking using a tryptic digest of 16 proteins to maximize peptide
      identifications and minimize band broadening. We performed comparative proteomic
      analysis of a dilution series using CE and nanoflow liquid chromatography (nLC).
      We found complementary peptide and protein identifications with larger quantities
      (100 ng) of a Pyrococcus furiosus tryptic digest, but with mass-limited amounts
      (5 ng) CE was 3 times more effective at identifying proteins. We attribute these
      gains in sensitivity to lower noise levels with the porous CE sprayer,
      illustrated by better signal-to-noise ratios of peptide precursor ions and
      associated higher XCorr values of identified peptides when compared directly to
      nLC. From comparative analysis of SPME-tITP-CE with direct injection CE, the SPME
      tITP process improved comprehensiveness and sensitivity.

PMID- 23004023
TI  - Constituents of Hondurian propolis with inhibitory effects on Saccharomyces
      cerevisiae multidrug resistance protein Pdr5p.
AB  - Chemical investigation of a propolis sample collected in Honduras has led to the
      isolation of the new (E,Z)-cinnamyl cinnamate (2) together with 14 known
      compounds: 6 cinnamic ester derivatives, 2 flavanones, 1 chalcone, 2 triterpenes,
      and 3 aromatic acids. Structural determination was accomplished by spectroscopic
      analysis, particularly two-dimensional (2D) nuclear magnetic resonance (NMR) and
      electrospray ionization-tandem mass spectrometry (ESI-MS/MS) techniques.
      Futhermore, we checked the ability of the propolis extract and the most
      representative compounds of each class (1, 5, 8, and 10) to inhibit the activity
      of Pdr5p, a protein responsible for a multidrug resistance phenotype in yeast.
      The present study appears to be the first report on Honduras propolis. Isolated
      cinnamic ester derivatives indicated the possible relation between Honduras
      propolis and the genus  Liquidambar .

PMID- 23004025
TI  - Factors impacting the departure rates of female and male junior medical school
      faculty: evidence from a longitudinal analysis.
AB  - BACKGROUND: High rates of attrition have been documented nationally in assistant
      professor faculty of U.S. medical schools. Our objective was to investigate the
      association of individual level risk factors, track of academic appointment, and
      use of institutional leave policies with departure in junior faculty of a
      research-intensive school of medicine. METHODS: Participants included 901 faculty
      newly hired as assistant professors from July 1, 1999, through December 30, 2007,
      at the Perelman School of Medicine at the University of Pennsylvania. The faculty
      affairs database was used to determine demographics, hiring date, track of
      appointment, track changes, time to departure, and use of work-life policies for
      an extension of the probationary period for mandatory review, reduction in
      duties, and leave of absence. RESULTS: Over one quarter (26.7%) of faculty
      departed during follow-up. Faculty appointed on the clinician educator or
      research tracks were at increased risk of departure compared to the tenure track
      (hazard ratio [HR] 1.87, confidence interval, [CI] 1.28-2.71; HR 4.50, CI 2.91
      6.96; respectively). Women appointed on the clinician educator track were at
      increased risk of departure compared to men (HR 1.46, CI 1.04-2.05). Faculty who
      took an extension of the probationary period were at decreased risk of departure
      (HR 0.36, CI 0.25-0.52). CONCLUSIONS: At this institution, junior faculty on the
      tenure track were least likely to depart before their mandatory review compared
      to faculty on the clinician educator or research tracks. Female assistant
      professors on the clinician educator track are of significant risk for departure.
      Taking advantage of the work-life policy for an extension of the probationary
      period protects against attrition.

PMID- 23004024
TI  - In vivo pharmacological interactions between a type II positive allosteric
      modulator of alpha7 nicotinic ACh receptors and nicotinic agonists in a murine
      tonic pain model.
AB  - BACKGROUND AND PURPOSE: The alpha7 nicotinic ACh receptor subtype is abundantly
      expressed in the CNS and in the periphery. Recent evidence suggests that alpha7
      nicotinic ACh receptor (nAChR) subtypes, which can be activated by an endogenous
      cholinergic tone comprising ACh and the alpha7 agonist choline, play an important
      role in chronic pain and inflammation. In this study, we evaluated whether type
      II alpha7 positive allosteric modulator PNU-120596 induces antinociception on its
      own and in combination with choline in the formalin pain model. EXPERIMENTAL
      APPROACH: We assessed the effects of PNU-120596 and choline and the nature of
      their interactions in the formalin test using an isobolographic analysis. In
      addition, we evaluated the interaction of PNU-120596 with PHA-54613, an exogenous
      selective alpha7 nAChR agonist, in the formalin test. Finally, we assessed the
      interaction between PNU-120596 and nicotine using acute thermal pain, locomotor
      activity, body temperature and convulsing activity tests in mice. KEY RESULTS: We
      found that PNU-120596 dose-dependently attenuated nociceptive behaviour in the
      formalin test after systemic administration in mice. In addition, mixtures of PNU
      120596 and choline synergistically reduced formalin-induced pain. PNU-120596
      enhanced the effects of nicotine and alpha7 agonist PHA-543613 in the same test.
      In contrast, PNU-120596 failed to enhance nicotine-induced convulsions,
      hypomotility and antinociception in acute pain models. Surprisingly, it enhanced
      nicotine-induced hypothermia via activation of alpha7 nAChRs. CONCLUSIONS AND
      IMPLICATIONS: Our results demonstrate that type II alpha7 positive allosteric
      modulators produce antinociceptive effects in the formalin test through a
      synergistic interaction with the endogenous alpha7 agonist choline.

PMID- 23004027
TI  - Masking effect of modern technology on annual rhythms: variation in births and
      deaths in a single family history over five centuries.

PMID- 23004028
TI  - Self-efficacy and health status improve after a wellness program in persons with
      multiple sclerosis.
AB  - PURPOSE: To determine if an intensive wellness program for persons with MS
      results in improved self-efficacy, quality of life (QOL), or physical activity
      outcomes. METHODS: 129 subjects participated in one of seven 4-day
      interdisciplinary educational wellness programs throughout the United States.
      This intervention was based on the philosophy that health management is important
      to disease management. The program consisted of psychological and physiological
      evaluations, lectures and workshops. Before the intervention and after at 1, 3
      and 6 months, self-efficacy (MS Self-Efficacy Scale, MSSE, control), health
      related QOL (SF-36) and physical activity (Physical Activity Scale for Persons
      with Physical Disabilities, PASAID) was assessed. RESULTS: Improvements were
      noted at 1, 3 and 6 months post-intervention. Those present at 6 months included,
      MSSE, role physical, vitality and mental health scales of the SF-36. PASAID did
      not change. Improvements were independent of disability (EDSS). CONCLUSION: A 4
      day multidisciplinary educational wellness program can result in improvement in
      self-efficacy and health-related QOL in persons with MS and can be stable up to
      at least 6 months. Improvements do not depend on degree of disability.

PMID- 23004029
TI  - Anaphylaxis in an emergency setting - elicitors, therapy and incidence of severe
      allergic reactions.
AB  - BACKGROUND: Anaphylaxis is a severe potentially life-threatening hypersensitivity
      reaction with an estimated lifetime prevalence of 0.5-2.0%. The prevalence and
      incidence of anaphylactic reactions in Germany are unknown. We therefore assessed
      anaphylactic patients seen by emergency physicians in the Berlin area covering 4
      million people. METHODS: A standardised questionnaire was filled from 2008 to
      2010 by the emergency physicians. RESULTS: A total of 333 cases of anaphylaxis
      were reported. 295 of these met the inclusion criteria for severity and were
      analysed. 13.9% (n = 41) were reactions with respiratory symptoms, 25.4% (n = 75)
      with cardiovascular, and in 60.7% (n = 179) of cases, respiratory and
      cardiovascular symptoms were reported. Two reactions were fatal. The most common
      elicitors were food products (32.2%), drugs (29.2%) and insect venom (19.3%). The
      most frequently given drugs were corticoids and antihistamines, but not
      adrenaline. For 2008, the calculated incidence was 4.5 per 100 000. CONCLUSIONS:
      Our data show that food products are frequent elicitors of severe allergic
      reactions in the general population including children and adults. It unravels a
      strong underuse of adrenaline by emergency physicians, not reflecting treatment
      protocols according to the current guidelines. As data obtained from allergists
      reveal a different rank order of elicitors, this study suggests that food
      allergic adult patients may present a risk population and should receive more
      attention by allergists.

PMID- 23004222
TI  - Photophysical probes for multiple-redox and multiple-excited-state interactions
      in molecular aggregates.
AB  - Photosynthesis takes place through a highly efficient series of energy, electron,
      and proton transfers initiated by absorption of one or more photons within the
      visible region of the solar spectrum. Because of the presence of multiple
      chromophores needed for effective light harvesting, extinction coefficients must
      be very high. The absorbing multiunit array is held within a rigidly arranged
      structure that facilitates each electron hop. A fully artificial, yet biomimetic,
      alternative to photosynthesis that produces fuels directly and efficiently from
      sunlight and simple low molecular weight molecules would change the world.
      Achieving this goal requires a detailed understanding of the mechanisms of the
      key steps of the complex chemical and photochemical processes taking place in
      natural photosynthesis. One of these mechanisms relies on light harvesting to
      initiate multiple-step sequences to obtain combustible molecules suitable for
      burning. In particular, we are devising and testing photophysical models with
      characteristics that facilitate multiple electron transfers within a single
      aggregate and are directly relevant to light harvesting. We focus on structural
      features that promote photoinduced electron transfer at high dye densities,
      placed for optimal solar utilization and catalysis. The reaction producing oxygen
      is further complicated by the need for four electrons to complete the sequence,
      even though the first initiation step is presumably absorption of a single
      photon. Therefore we explore steps that accumulate charge or have the potential
      to do so. We also emphasize the synthesis of model systems that probe the
      complexity of individual steps. This Account examines the factors that influence
      the efficiency of electron redistribution in multiple-dye, multiple-excited
      state, and multiple-redox equivalent arrays. Such knowledge will allow us to
      optimize the efficiency of electron migration and may contribute to a better
      understanding of multiple-equivalent light harvesting events by which
      photosynthetic energy storage takes place.

PMID- 23004223
TI  - Design of chimeric expression elements that confer high-level gene activity in
      chromoplasts.
AB  - Non-green plastids, such as chromoplasts, generally have much lower activity of
      gene expression than chloroplasts in photosynthetically active tissues.
      Suppression of plastid genes in non-green tissues occurs through a complex
      interplay of transcriptional and translational control, with the contribution of
      regulation of transcript abundance versus translational activity being highly
      variable between genes. Here, we have investigated whether the low expression of
      the plastid genome in chromoplasts results from inherent limitations in gene
      expression capacity, or can be overcome by designing appropriate combinations of
      promoters and translation initiation signals in the 5' untranslated region (5'
      UTR). We constructed chimeric expression elements that combine promoters and 5'
      UTRs from plastid genes, which are suppressed during chloroplast-to-chromoplast
      conversion in Solanum lycopersicum (tomato) fruit ripening, either just at the
      translational level or just at the level of mRNA accumulation. These chimeric
      expression elements were introduced into the tomato plastid genome by stable
      chloroplast transformation. We report the identification of promoter-UTR
      combinations that confer high-level gene expression in chromoplasts of ripe
      tomato fruits, resulting in the accumulation of reporter protein GFP to up to 1%
      of total cellular protein. Our work demonstrates that non-green plastids are
      capable of expressing genes to high levels. Moreover, the chimeric cis-elements
      for chromoplasts developed here are widely applicable in basic and applied
      research using transplastomic methods.

PMID- 23004224
TI  - Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts
      undergoing field castration.
AB  - REASONS FOR PERFORMING THE STUDY: The use of alfaxalone and medetomidine
      administered as an i.v. infusion to maintain anaesthesia has not previously been
      reported in the horse. OBJECTIVES: To investigate the use of alfaxalone in
      hydroxpropyl-beta-cyclodextrin (Alfaxan) and medetomidine infusion as a field
      anaesthetic for short-term surgical procedures in the horse. HYPOTHESIS:
      Alfaxalone-medetomidine anaesthesia is suitable for short-term field anaesthesia
      in horses. METHODS: Eleven healthy colts underwent 45 min of anaesthesia with an
      i.v. infusion of alfaxalone (2 mg/kg bwt/h) and medetomidine (5 MUg/kg bwt/h) for
      routine field castration. Horses were premedicated with i.v. acepromazine (0.03
      mg/kg bwt), medetomidine (7 MUg/kg bwt) and guaiphenesin (35 mg/kg bwt) before
      i.v. induction with alfaxalone (1 mg/kg bwt). Colts were intubated with an
      endotracheal tube and 100% oxygen insufflated at 10 l/min. The physiological
      variables monitored included pulse rate, respiratory rate, direct arterial blood
      pressure, arterial blood gases and the quality of the inductions and recoveries
      were scored. RESULTS: Overall, the anaesthetic period and surgical conditions
      were acceptable and the quality of the anaesthetic inductions and recoveries was
      good to excellent. All colts stood on their first attempt (mean +/- s.d.) 37 +/-
      13.5 min after the infusion was stopped. During anaesthesia, cardiopulmonary
      data, presented as range of mean values at each time point were: heart rate: 45
      47 beats/min; mean blood pressure: 104-112 mmHg; respiratory rate: 8 breaths/min;
      PaO2 : 117-172 mmHg; PaCO2 : 50-56 mmHg and pH 7.34-7.37. CONCLUSIONS AND
      POTENTIAL RELEVANCE: The co-administration of alfaxalone and medetomidine as an
      i.v. infusion after anaesthetic induction with alfaxalone was suitable for short
      term field anaesthesia in the horse.

PMID- 23004225
TI  - Comparison of success rate of ultrasound-guided sciatic and femoral nerve block
      and neurostimulation in children with arthrogryposis multiplex congenita: a
      randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVES: Arthrogryposis multiplex congenital is hallmarked with
      immobile joints and muscle fibrosis. The main objective of this study was to
      compare the success rate of ultrasound-guided sciatic and femoral nerve blocks
      with nerve stimulations in children diagnosed with distal arthrogryposis
      multiplex congenita. METHOD: Sixty children aged 8 months to 2 years posted for
      foot surgery were randomly assigned to group NS and group US of 30 each. Under
      general anesthesia, femoro-sciatic block was performed with nerve stimulator
      guidance in group NS and ultrasound guidance in group US. RESULTS: Group NS: 23
      of 30 (76.7%) children showed ankle movement with sciatic neurostimulation. In 7
      (23.6%), distal motor response could not be elicited and the block was abandoned.
      Out of 23 children who could be given femoral block, in 12 (52%) patients
      quadriceps contractions were not elicited and fascia iliaca block was given. All
      23 blocks were successful. CHIPPS score at 1, 4, 6, 8, and 10 h was 1.05 +/-
      0.90, 1.82 +/- 1.18, 3.36 +/- 1.65, 2.23 +/- 2.02, and 1.18 +/- 1.14,
      respectively. Group US: In 29 of 30 patients (96.6%), sciatic nerve was
      visualized with ultrasonography. All 29 children received femoral block, and they
      were successful. The odds of success in group US were 8.9 (95% confidence
      interval [1.0, 77.9]) as compared with NS group. The difference in success rate
      was statistically significant (P = 0.026). The analgesic duration difference in
      the US and NS groups was a mean 7.62 +/- 0.57 h in group NS and 8.60 +/- 0.66 h
      in group US (statistically significant [P < 0.001]). CHIPPS score at 1, 4, 6, 8,
      and 10 h was 0.79 +/- 0.96, 1.61 +/- 0.92, 2.96 +/- 1.04, 2.36 +/- 2.54, and 1.14
      +/- 1.01, respectively. The difference between the CHIPPS score was not
      statistically significant. CONCLUSION: Ultrasonography significantly increases
      the success rate of sciatic and femoral block in arthrogryposis.

PMID- 23004226
TI  - In this issue--October 2012.

PMID- 23004227
TI  - Behavioural responses of lambs to plastic clips as an alternative procedure to
      mulesing.
AB  - OBJECTIVE: Compare the effects on the behaviour of lambs of applying occlusive
      plastic clips, as an alternative procedure to surgical mulesing, with tail
      docking, surgical mulesing and a control treatment. PROCEDURE: We allocated 48 6
      7-week-old Merino lambs to four treatment groups: plastic clips (Clip); surgical
      mulesing (Mules); tail docking with a rubber ring (Tail ring); no treatment
      (Control). For each posture and behaviour observed on each of the 4 days post
      treatment, a Dunnett's multiple comparison test was used to simultaneously
      compare the Clip treatment with each of the comparator treatments (Control, Tail
      ring and Mules treatments). RESULTS: Most of the significant differences (P <
      0.05) detected between the comparator treatments occurred on day 1. For four of
      these measurements, the Clip treatment differed (P < 0.01) from the Mules
      treatment, but from not the Control and Tail ring treatments: the Clip lambs
      spent less time standing immobile not interacting with ground, hay or feeder,
      less time standing immobile head down not interacting with ground, hay or feeder,
      more time walking and more time interacting with ground, hay or feeder.
      CONCLUSION: These behavioural results, together with previous behavioural and
      physiological research, indicate that the effect on lamb welfare of applying
      occlusive clips is less than that of surgical mulesing.

PMID- 23004228
TI  - Coronavirus infection in intensively managed cattle with respiratory disease.
AB  - BACKGROUND: A detailed laboratory investigation identified bovine coronavirus
      (BCoV) as the aetiological agent in an outbreak of respiratory disease at a semi
      intensive beef cattle feedlot in south-east Australia. The outbreak caused 30%
      morbidity in the resident population and also affected two cohorts of cattle that
      were newly introduced to the property. METHODS: At slaughter, pulmonary
      consolidation and inflammatory lesions in the trachea were identified in 15 of 49
      animals. Pasteurella multocida or Histophilus somni was cultured from 3 of 7
      animals with lesions. Histopathological examination revealed multifocal non
      suppurative bronchointerstitial pneumonia with formation of epithelial syncytial
      cells, sometimes associated with suppurative bronchopneumonia. RESULTS: BCoV was
      detected in nasal swabs and pulmonary lesions using real-time reverse
      transcriptase-polymerase chain reaction (qRT-PCR) assay and virus isolation.
      There was serological evidence of previous exposure to bovine viral diarrhoea
      virus, bovine respiratory syncytial virus and bovine parainfluenza virus type 3,
      but not to bovine herpesvirus type 1. None of these viral pathogens or Mycoplasma
      bovis was identified by qRT-PCR. CONCLUSION: This is believed to be the first
      report of BCoV in association with bovine respiratory disease complex in
      Australia.

PMID- 23004229
TI  - Feasibility of infrared spectroscopy with pattern recognition techniques to
      identify a subpopulation of mares at risk of producing foals diagnosed with
      failure of transfer of passive immunity.
AB  - OBJECTIVE: To assess the feasibility of a serum-based test using infrared
      spectroscopy to identify a subpopulation of mares at risk of producing foals
      susceptible to failure of passive transfer of immunity (FPT) because of mare
      associated factors. MATERIALS AND METHODS: Serum was collected from post
      parturient mares (n = 126) and their foals at 24-72 h of age. A radial
      immunodiffusion IgG test was used to determine each foal's serum IgG
      concentration. Infrared absorbance spectra of dam sera were collected in the wave
      number range of 400-4000 cm(-1). Following data preprocessing, pattern
      recognition techniques were used to identify spectroscopic information capable of
      distinguishing between mares with FPT foals and those with normal foals. The
      sensitivity and specificity of infrared spectroscopy to detect risk-positive
      mares were calculated. RESULTS: Five wave number regions were identified as
      optimal for distinguishing between the two groups of mares: 740.9-785.2 cm(-1),
      796.8-816.0 cm(-1), 970.4-993.5 cm(-1), 1371.6-1406.3 cm(-1) and 1632.0-1659.0
      cm(-1). Based upon the infrared spectroscopic information within these
      discriminatory subregions, the spectra provided the risk status of the mares with
      a classification success rate of 81.0%. The sensitivity of the classification
      system was 85.7% and specificity was 80.0%. CONCLUSION: This preliminary study
      demonstrates that infrared spectra of dam serum have the potential to provide the
      basis for a new periparturient screening method for a subpopulation of mares at
      risk of having a foal susceptible to FPT. Further development may provide an
      economic and rapid technique for the pre-parturient assessment of mares.

PMID- 23004230
TI  - Pyogranulomatous lesion causing neurological signs localised to the sacral region
      in a horse.
AB  - This case report describes neurological signs associated with a pyogranulomatous
      lesion within the sacral vertebral canal of a horse. The clinical findings
      included urinary overflow incontinence and reduced anal, perianal and tail tone.
      The horse failed to respond to medical management and a guarded prognosis for
      return to athletic performance initiated the decision for euthanasia.

PMID- 23004231
TI  - Ken Ferguson: 1921-2011: leader in animal science.

PMID- 23004232
TI  - Clinical evaluation of alfaxalone as an anaesthetic induction agent in cats less
      than 12 weeks of age.
AB  - OBJECTIVE: To assess the clinical suitability of alfaxalone as an anaesthetic
      induction and maintenance agent for kittens aged less than 12 weeks. MATERIALS
      AND METHODS: The study group comprised 34 kittens aged less than 12 weeks that
      were presented for surgical desexing. They were aged by dentition, examined and
      weighed prior to premedication with acepromazine, atropine and morphine. At 20-30
      min after premedication, animals were anaesthetised with intravenous alfaxalone
      administered to effect, using a target maximum expected dose of 5 mg/kg. All cats
      were intubated: 25 were maintained with isoflurane in oxygen administered with a
      non-rebreathing circuit and 8 were maintained by supplemental intravenous
      administration of alfaxalone. Subjective measures of anaesthetic quality and
      vital signs were recorded from enrolment to recovery. Cats receiving supplemental
      alfaxalone for maintenance were evaluated for time to first supplemental dose and
      the total dose of supplemental alfaxalone (mg/kg/h). Descriptive and comparative
      statistics were used to analyse and present collected data. RESULTS: The mean (+/
      SD) dose of alfaxalone for induction was 4.7 +/- 0.5 mg/kg body weight.
      Subjective measures of anaesthetic quality indicated acceptable induction,
      maintenance and recovery standards. Measured cardiovascular and respiratory
      parameters were well maintained. CONCLUSION: Alfaxalone in 2-hydroxypropyl-beta
      cyclodextrin (Alfaxan(r)) is a suitable injectable anaesthetic induction agent
      for juvenile cats aged less than 12 weeks requiring anaesthesia. Maintenance of
      anaesthesia with supplemental doses of alfaxalone may be a suitable alternative
      in kittens when the use of inhalant anaesthetic maintenance is not feasible.

PMID- 23004233
TI  - Hypotension and pruritus induced by neuraxial anaesthesia in a cat.
AB  - Although preventive epidural morphine administration with bupivacaine is
      effective in producing long-lasting analgesia, neuraxial anaesthesia can cause
      cardiovascular depression and pruritus. This report presents the development and
      treatment of hypotension and pruritus after intrathecal morphine and bupivacaine
      administration in a 3-year-old female spayed Domestic Short-hair cat presented
      for surgical repair of a torn right cranial cruciate ligament. Opioid-induced
      pruritus is not usually considered a frequently occurring complication, but may
      be easily misinterpreted as being dysphoria in recovery. It can be treated by
      administration of ondansetron, with human patients usually responding within 30
      min after treatment.

PMID- 23004235
TI  - Vet Ed revamped!

PMID- 23004234
TI  - Prevalence of koala retrovirus in geographically diverse populations in
      Australia.
AB  - OBJECTIVE: To determine the prevalence of koala retrovirus (KoRV) in selected
      koala populations and to estimate proviral copy number in a subset of koalas.
      METHODS: Blood or tissue samples from 708 koalas in Queensland, New South Wales,
      Victoria and South Australia were tested for KoRV pol provirus gene using
      standard polymerase chain reaction (PCR), nested PCR and real-time PCR (qPCR).
      RESULTS: Prevalence of KoRV provirus-positive koalas was 100% in four regions of
      Queensland and New South Wales, 72.2% in mainland Victoria, 26.6% on four
      Victorian islands and 14.8% on Kangaroo Island, South Australia. Estimated
      proviral copy number per cell in four groups of koalas from Queensland and
      Victoria showed marked variation, ranging from a mean of 165 copies per cell in
      the Queensland group to 1.29 * 10(-4)  copies per cell in one group of Victorian
      koalas. CONCLUSIONS: The higher prevalence of KoRV-positive koalas in the north
      of Australia and high proviral loads in Queensland koalas may indicate KoRV
      entered and became endogenous in the north and is spreading southwards. It is
      also possible there are genetic differences between koalas in northern and
      southern Australia that affect susceptibility to KoRV infection or
      endogenisation, or that environmental factors affecting transmission in northern
      states are absent or uncommon in southern regions. Although further studies are
      required, the finding of proviral copy numbers orders of magnitude lower than
      what would be expected for the presence of a single copy in every cell for many
      Victorian animals suggests that KoRV is not endogenous in these animals and
      likely reflects ongoing exogenous infection.

PMID- 23004236
TI  - Radiographic evaluation of marginal bone levels around dental implants with
      different designs after 1 year.
AB  - OBJECTIVE: The aim of this study was to use intra-oral radiographs to evaluate
      changes in marginal bone levels around three different implant designs after 1
      year. MATERIALS AND METHODS: Three implant designs; two with a straight and one
      with a conical design, were placed adjacent to each other in the partially
      edentulous areas of 25 patients. The patients received 46 implants with a
      straight design (All fit SSO and SPI-element) and 29 implants with a conical
      design (SPI-contact). Two-way repeated analysis of variance (ANOVA) was used to
      evaluate the marginal bone changes in each group at 12 months follow-up (p <
      0.05). RESULTS: None of the implants had failed by the end of this study. After
      12 months, significant differences were noted in the amount of alveolar bone loss
      recorded between the All fit SSO and SPI implants (p < 0.05). Mean crestal bone
      loss was 0.88 +/- 0.43 mm for the All fit, 0.61 +/- 0.34 mm for the SPI contact
      and 0.54 +/- 0.27 mm for the SPI element implants. CONCLUSIONS: The results of
      this study demonstrate that straight (cylindrical) implants with shorter high
      polish surface displayed less bone resorption.

PMID- 23004237
TI  - Hermeneutic reading of classic texts.
AB  - The purpose of this article is to broaden the understandinfg of the hermeneutic
      reading of classic texts. The aim is to show how the choice of a specific
      scientific tradition in conjunction with a methodological approach creates the
      foundation that clarifies the actual realization of the reading. This hermeneutic
      reading of classic texts is inspired by Gadamer's notion that it is the
      researcher's own research tradition and a clearly formulated theoretical
      fundamental order that shape the researcher's attitude towards texts and create
      the starting point that guides all reading, uncovering and interpretation. The
      researcher's ethical position originates in a will to openness towards what is
      different in the text and which constantly sets the researcher's preunderstanding
      and research tradition in movement. It is the researcher's attitude towards the
      text that allows the text to address, touch and arouse wonder. Through a
      flexible, lingering and repeated reading of classic texts, what is different
      emerges with a timeless value. The reading of classic texts is an act that may
      rediscover and create understanding for essential dimensions and of human beings'
      reality on a deeper level. The hermeneutic reading of classic texts thus brings
      to light constantly new possibilities of uncovering for a new envisioning and
      interpretation for a new understanding of the essential concepts and phenomena
      within caring science. 

PMID- 23004238
TI  - Studies toward the unique pederin family member psymberin: full structure
      elucidation, two alternative total syntheses, and analogs.
AB  - Two synthetic approaches to psymberin have been accomplished. A highly convergent
      first generation synthesis led to the complete stereochemical assignment and
      demonstrated that psymberin and irciniastatin A are identical compounds. This
      synthesis featured a diastereoselective aldol coupling between the aryl fragment
      and a central tetrahydropyran core and a novel one-pot procedure to convert an
      amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal
      reminiscent of psymberin. The highlights of the second generation synthesis
      include an efficient iridium-catalyzed enantioselective bisallylation of
      neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction
      sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were
      achieved in 17-18 steps (longest linear sequence, ~14-15 isolations) from 3
      fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps
      each. This convergent approach allowed for the preparation of sufficient amounts
      of psymberin (~ 0.5 g) for follow-up biological studies. Meanwhile, our highly
      flexible strategy enabled the design and synthesis of multiple analogs, including
      a psymberin-pederin hybrid, termed psympederin, that proved crucial to a
      comprehensive understanding of the chemical biology of psymberin and related
      compounds that will be described in a subsequent manuscript.

PMID- 23004239
TI  - Thermal pure quantum states at finite temperature.
AB  - An equilibrium state can be represented by a pure quantum state, which we call a
      thermal pure quantum (TPQ) state. We propose a new TPQ state and a simple method
      of obtaining it. A single realization of the TPQ state suffices for calculating
      all statistical-mechanical properties, including correlation functions and
      genuine thermodynamic variables, of a quantum system at finite temperature.

PMID- 23004240
TI  - Quantum geometric phase in Majorana's stellar representation: mapping onto a many
      body Aharonov-Bohm phase.
AB  - The (Berry-Aharonov-Anandan) geometric phase acquired during a cyclic quantum
      evolution of finite-dimensional quantum systems is studied. It is shown that a
      pure quantum state in a (2J+1)-dimensional Hilbert space (or, equivalently, of a
      spin-J system) can be mapped onto the partition function of a gas of independent
      Dirac strings moving on a sphere and subject to the Coulomb repulsion of 2J fixed
      test charges (the Majorana stars) characterizing the quantum state. The geometric
      phase may be viewed as the Aharonov-Bohm phase acquired by the Majorana stars as
      they move through the gas of Dirac strings. Expressions for the geometric
      connection and curvature, for the metric tensor, as well as for the multipole
      moments (dipole, quadrupole, etc.), are given in terms of the Majorana stars.
      Finally, the geometric formulation of the quantum dynamics is presented and its
      application to systems with exotic ordering such as spin nematics is outlined.

PMID- 23004241
TI  - Measurable quantum geometric phase from a rotating single spin.
AB  - We demonstrate that the internal magnetic states of a single nitrogen-vacancy
      defect, within a rotating diamond crystal, acquire geometric phases. The
      geometric phase shift is manifest as a relative phase between components of a
      superposition of magnetic substates. We demonstrate that under reasonable
      experimental conditions a phase shift of up to four radians could be measured.
      Such a measurement of the accumulation of a geometric phase, due to macroscopic
      rotation, would be the first for a single atom-scale quantum system.

PMID- 23004242
TI  - Correlations and pair formation in a repulsively interacting Fermi gas.
AB  - A degenerate Fermi gas is rapidly quenched into the regime of strong effective
      repulsion near a Feshbach resonance. The spin fluctuations are monitored using
      speckle imaging and, contrary to several theoretical predictions, the samples
      remain in the paramagnetic phase for an arbitrarily large scattering length. Over
      a wide range of interaction strengths a rapid decay into bound pairs is observed
      over times on the order of 10h/E(F), preventing the study of equilibrium phases
      of strongly repulsive fermions. Our work suggests that a Fermi gas with strong
      short-range repulsive interactions does not undergo a ferromagnetic phase
      transition.

PMID- 23004243
TI  - Role reversal in a Bose-condensed optomechanical system.
AB  - We analyze the optomechanicslike properties of a Bose-Einstein condensate (BEC)
      trapped inside an optical resonator and driven by both a classical and a
      quantized light field. We find that this system exhibits the nature of role
      reversal between the matter-wave field and the quantized light field. As a
      result, the matter-wave field now plays the role of the quantized light field,
      and the quantized light field behaves like a movable mirror, in contrast to the
      familiar situation in BEC-based cavity optomechanics [Brennecke et al., Science
      322, 235 (2008); Murch et al., Nature Phys. 4, 561 (2008)]. We demonstrate that
      this system can lead to the creation of a variety of nonclassical matter-wave
      fields, in particular, cat states, and discuss several possible protocols to
      measure their Wigner function.

PMID- 23004244
TI  - Enhanced subthreshold e+ e- production in short laser pulses.
AB  - The emission of e+ e- pairs off a probe photon propagating through a polarized
      short-pulsed electromagnetic (e.g., laser) wave field is analyzed. A significant
      increase of the total cross section of pair production in the subthreshold region
      is found for decreasing laser pulse duration even in the case of moderate laser
      pulse intensities.

PMID- 23004245
TI  - Experimental Schmidt decomposition and state independent entanglement detection.
AB  - We introduce an experimental procedure for the detection of quantum entanglement
      of an unknown quantum state with a small number of measurements. The method
      requires neither a priori knowledge of the state nor a shared reference frame
      between the observers and can thus be regarded as a perfectly state-independent
      entanglement witness. The scheme starts with local measurements, possibly
      supplemented with suitable filtering, which essentially establishes the Schmidt
      decomposition for pure states. Alternatively we develop a decision tree that
      reveals entanglement within few steps. These methods are illustrated and verified
      experimentally for various entangled states of two and three qubits.

PMID- 23004246
TI  - Black-box superconducting circuit quantization.
AB  - We present a semiclassical method for determining the effective low-energy
      quantum Hamiltonian of weakly anharmonic superconducting circuits containing
      mesoscopic Josephson junctions coupled to electromagnetic environments made of an
      arbitrary combination of distributed and lumped elements. A convenient basis,
      capturing the multimode physics, is given by the quantized eigenmodes of the
      linearized circuit and is fully determined by a classical linear response
      function. The method is used to calculate numerically the low-energy spectrum of
      a 3D transmon system, and quantitative agreement with measurements is found.

PMID- 23004247
TI  - Optimal correlations in many-body quantum systems.
AB  - Information and correlations in a quantum system are closely related through the
      process of measurement. We explore such relation in a many-body quantum setting,
      effectively bridging between quantum metrology and condensed matter physics. To
      this aim we adopt the information-theory view of correlations and study the
      amount of correlations after certain classes of positive-operator-valued
      measurements are locally performed. As many-body systems, we consider a one
      dimensional array of interacting two-level systems (a spin chain) at zero
      temperature, where quantum effects are most pronounced. We demonstrate how the
      optimal strategy to extract the correlations depends on the quantum phase through
      a subtle interplay between local interactions and coherence.

PMID- 23004248
TI  - Increasing entanglement monotones by separable operations.
AB  - Quantum entanglement is fundamentally related to the operational setting of local
      quantum operations and classical communication (LOCC). A more general class of
      operations known as separable operations (SEP) is often employed to approximate
      LOCC, but the exact difference between LOCC and SEP is unknown. In this letter,
      we compare the two classes in performing particular tripartite to bipartite
      entanglement conversions and report a gap as large as 12.5% between SEP and LOCC,
      which is the first known appreciable gap between the classes. Our results rely on
      constructing a computable entanglement monotone with a clear operational meaning
      that, unlike all other such monotones previously studied, is not monotonic under
      SEP. Finally, we prove the curious fact that convergent sequences of LOCC
      protocols need not be LOCC feasible in the limit.

PMID- 23004249
TI  - Symmetry-protected phases for measurement-based quantum computation.
AB  - Ground states of spin lattices can serve as a resource for measurement-based
      quantum computation. Ideally, the ability to perform quantum gates via
      measurements on such states would be insensitive to small variations in the
      Hamiltonian. Here, we describe a class of symmetry-protected topological orders
      in one-dimensional systems, any one of which ensures the perfect operation of the
      identity gate. As a result, measurement-based quantum gates can be a robust
      property of an entire phase in a quantum spin lattice, when protected by an
      appropriate symmetry.

PMID- 23004251
TI  - Faster diffusion across an irregular boundary.
AB  - We investigate how the shape of a heat source may enhance global heat transfer at
      short time. An experiment is described that allows us to obtain a direct
      visualization of heat propagation from a prefractal radiator. We show, both
      experimentally and numerically, that irregularly shaped passive coolers rapidly
      dissipate at short times, but their efficiency decreases with time. The de Gennes
      scaling argument is shown to be only a large scale approximation, which is not
      sufficient to describe adequately the temperature distribution close to the
      irregular frontier. This work shows that radiators with irregular surfaces permit
      increased cooling of pulsed heat sources.

PMID- 23004250
TI  - Partial synchronization of stochastic oscillators through hydrodynamic coupling.
AB  - Holographic optical tweezers are used to construct a static bistable optical
      potential energy landscape where a brownian particle experiences restoring forces
      from two nearby optical traps and undergoes thermally activated transitions
      between the two energy minima. Hydrodynamic coupling between two such systems
      results in their partial synchronization. This is interpreted as an emergence of
      higher mobility pathways, along which it is easier to overcome barriers to
      structural rearrangement.

PMID- 23004252
TI  - Fluctuation relation for heat.
AB  - We present a fluctuation relation for heat dissipation in a nonequilibrium
      system. A nonequilibrium work is known to obey the fluctuation theorem in any
      time interval t. Heat, which differs from work by an energy change, is shown to
      satisfy a modified fluctuation relation. Modification is brought about by the
      correlation between heat and energy change during nonequilibrium processes whose
      effect may not be negligible even in the t->infinity limit. The fluctuation
      relation is derived for overdamped Langevin equation systems, and tested in a
      linear diffusion system.

PMID- 23004253
TI  - Support for the thermal origin of the pioneer anomaly.
AB  - We investigate the possibility that the anomalous acceleration of the Pioneer 10
      and 11 spacecraft is due to the recoil force associated with an anisotropic
      emission of thermal radiation off the vehicles. To this end, relying on the
      project and spacecraft design documentation, we constructed a comprehensive
      finite-element thermal model of the two spacecraft. Then, we numerically solve
      thermal conduction and radiation equations using the actual flight telemetry as
      boundary conditions. We use the results of this model to evaluate the effect of
      the thermal recoil force on the Pioneer 10 spacecraft at various heliocentric
      distances. We found that the magnitude, temporal behavior, and direction of the
      resulting thermal acceleration are all similar to the properties of the observed
      anomaly. As a novel element of our investigation, we develop a parametrized model
      for the thermal recoil force and estimate the coefficients of this model
      independently from navigational Doppler data. We find no statistically
      significant difference between the two estimates and conclude that, once the
      thermal recoil force is properly accounted for, no anomalous acceleration
      remains.

PMID- 23004254
TI  - Particle acceleration in turbulence and weakly stochastic reconnection.
AB  - In this Letter we analyze the energy distribution evolution of test particles
      injected in three dimensional (3D) magnetohydrodynamic (MHD) simulations of
      different magnetic reconnection configurations. When considering a single Sweet
      Parker topology, the particles accelerate predominantly through a first-order
      Fermi process, as predicted in  and demonstrated numerically in . When turbulence
      is included within the current sheet, the acceleration rate is highly enhanced,
      because reconnection becomes fast and independent of resistivity  and allows the
      formation of a thick volume filled with multiple simultaneously reconnecting
      magnetic fluxes. Charged particles trapped within this volume suffer several head
      on scatterings with the contracting magnetic fluctuations, which significantly
      increase the acceleration rate and results in a first-order Fermi process. For
      comparison, we also tested acceleration in MHD turbulence, where particles suffer
      collisions with approaching and receding magnetic irregularities, resulting in a
      reduced acceleration rate. We argue that the dominant acceleration mechanism
      approaches a second order Fermi process in this case.

PMID- 23004255
TI  - Robust constraint on cosmic textures from the cosmic microwave background.
AB  - Fluctuations in the cosmic microwave background (CMB) contain information which
      has been pivotal in establishing the current cosmological model. These data can
      also be used to test well-motivated additions to this model, such as cosmic
      textures. Textures are a type of topological defect that can be produced during a
      cosmological phase transition in the early Universe, and which leave
      characteristic hot and cold spots in the CMB. We apply bayesian methods to carry
      out a rigorous test of the texture hypothesis, using full-sky data from the
      Wilkinson Microwave Anisotropy Probe. We conclude that current data do not
      warrant augmenting the standard cosmological model with textures. We rule out at
      95% confidence models that predict more than 6 detectable cosmic textures on the
      full sky.

PMID- 23004256
TI  - Oscillons after inflation.
AB  - Oscillons are massive, long-lived, localized excitations of a scalar field. We
      show that in a class of well-motivated single-field models, inflation is followed
      by self resonance, leading to copious oscillon generation and a lengthy period of
      oscillon domination. These models are characterized by an inflaton potential
      which has a quadratic minimum and is shallower than quadratic away from the
      minimum. This set includes both string monodromy models and a class of
      supergravity inspired scenarios and is in good agreement with the current central
      values of the concordance cosmology parameters. We assume that the inflaton is
      weakly coupled to other fields so as not to quickly drain energy from the
      oscillons or prevent them from forming. An oscillon-dominated universe has a
      greatly enhanced primordial power spectrum on very small scales relative to that
      seen with a quadratic potential, possibly leading to novel gravitational effects
      in the early Universe.

PMID- 23004257
TI  - Gauge symmetries in spin-foam gravity: the case for "cellular quantization".
AB  - The spin-foam approach to quantum gravity rests on a quantization of BF theory
      using 2-complexes and group representations. We explain why, in dimension three
      and higher, this spin-foam quantization must be amended to be made consistent
      with the gauge symmetries of discrete BF theory. We discuss a suitable
      generalization, called "cellular quantization," which (1) is finite, (2) produces
      a topological invariant, (3) matches with the properties of the continuum BF
      theory, and (4) corresponds to its loop quantization. These results significantly
      clarify the foundations--and limitations--of the spin-foam formalism and open the
      path to understanding, in a discrete setting, the symmetry-breaking which reduces
      BF theory to gravity.

PMID- 23004258
TI  - Locally critical resistivities from umklapp scattering.
AB  - Efficient momentum relaxation through umklapp scattering, leading to a power law
      in temperature dc resistivity, requires a significant low energy spectral weight
      at finite momentum. One way to achieve this is via a Fermi surface structure,
      leading to the well-known relaxation rate Gamma~T2. We observe that local
      criticality, in which energies scale but momenta do not, provides a distinct
      route to efficient umklapp scattering. We show that umklapp scattering by an
      ionic lattice in a locally critical theory leads to Gamma~T(2Delta(k(L))). Here
      Delta(k(L))>=0 is the dimension of the (irrelevant or marginal) charge density
      operator J(t)(omega,k(L)) in the locally critical theory, at the lattice momentum
      k(L). We illustrate this result with an explicit computation in locally critical
      theories described holographically via Einstein-Maxwell theory in Anti-de Sitter
      spacetime. We furthermore show that scattering by random impurities in these
      locally critical theories gives a universal Gamma~(log(1/T))(-1).

PMID- 23004262
TI  - Compelling evidence of renormalons in QCD from high order perturbative
      expansions.
AB  - We compute the static self-energy of SU(3) gauge theory in four spacetime
      dimensions to order alpha20 in the strong coupling constant alpha. We employ
      lattice regularization to enable a numerical simulation within the framework of
      stochastic perturbation theory. We find perfect agreement with the factorial
      growth of high order coefficients predicted by the conjectured renormalon picture
      based on the operator product expansion.

PMID- 23004261
TI  - Z0-tagged jet event asymmetry in heavy-ion collisions at the CERN large hadron
      collider.
AB  - Tagged jet measurements provide a promising experimental channel to quantify the
      similarities and differences in the mechanisms of jet production in proton-proton
      and nucleus-nucleus collisions. We present the first calculation of the
      transverse momentum asymmetry of Z0/gamma*-tagged jet events in sqrt[s]=2.76  TeV
      reactions at the LHC. Our results combine the O(G(F)alpha(s)2) perturbative cross
      sections with the radiative and collisional processes that modify parton showers
      in the presence of dense strongly interacting matter. We find that a strong
      asymmetry is generated in central lead-lead reactions that has little sensitivity
      to the fluctuations of the underlying soft hadronic background. We present
      theoretical model predictions for its shape and magnitude.

PMID- 23004263
TI  - Calculation of transverse-momentum-dependent evolution for Sivers transverse
      single spin asymmetry measurements.
AB  - The Sivers transverse single spin asymmetry (TSSA) is calculated and compared at
      different scales using the transverse-momentum-dependent (TMD) evolution
      equations applied to previously existing extractions. We apply the Collins-Soper
      Sterman (CSS) formalism, using the version recently developed by Collins. Our
      calculations rely on the universality properties of TMD functions that follow
      from the TMD-factorization theorem. Accordingly, the nonperturbative input is
      fixed by earlier experimental measurements, including both polarized semi
      inclusive deep inelastic scattering (SIDIS) and unpolarized Drell-Yan (DY)
      scattering. It is shown that recent preliminary COMPASS measurements are
      consistent with the suppression prescribed by TMD evolution.

PMID- 23004259
TI  - Determination of the sign of the decay width difference in the B(s)(0) system.
AB  - The interference between the K+ K- S-wave and P-wave amplitudes in B(s)(0) ->
      J/psiK+ K- decays with the K+ K- pairs in the region around the phi(1020)
      resonance is used to determine the variation of the difference of the strong
      phase between these amplitudes as a function of K+ K- invariant mass. Combined
      with the results from our CP asymmetry measurement in B(s)(0) -> J/psiphi decays,
      we conclude that the B(s)(0) mass eigenstate that is almost CP = +1 is lighter
      and decays faster than the mass eigenstate that is almost CP = -1. This
      determines the sign of the decay width difference DeltaGamma(s) = Gamma(L) -
      Gamma(H) to be positive. Our result also resolves the ambiguity in the past
      measurements of the CP violating phase phi(s) to be close to zero rather than pi.
      These conclusions are in agreement with the standard model expectations.

PMID- 23004264
TI  - J/psi polarization at hadron colliders in nonrelativistic QCD.
AB  - With nonrelativistic QCD factorization, we present a full next-to-leading order
      computation of the polarization observable for J/psi production at hadron
      colliders including all important Fock states, i.e., 3S(1)([1,8]), 1S(0)([8]),
      and 3P(J)([8]). We find the 3P(J)([8]) channel contributes a positive
      longitudinal component and a negative transverse component, so the J/psi
      polarization puzzle may be understood as the transverse components canceling
      between the 3S(1)([8]) and 3P(J)([8]) channels, which results in mainly the
      unpolarized (even slightly longitudinally polarized) J/psi. This may give a
      possible solution to the long-standing J/psi polarization puzzle. Predictions for
      J/psi polarization at the LHC are also presented.

PMID- 23004265
TI  - Continuum effects and three-nucleon forces in neutron-rich oxygen isotopes.
AB  - We employ interactions from chiral effective field theory and compute binding
      energies, excited states, and radii for isotopes of oxygen with the coupled
      cluster method. Our calculation includes the effects of three-nucleon forces and
      of the particle continuum, both of which are important for the description of
      neutron-rich isotopes in the vicinity of the nucleus 24O. Our main results are
      the placement of the neutron drip line at 24O, the assignment of spins, parities
      and resonance widths for several low-lying states of the drip line nucleus, and
      an efficient approximation that incorporates the effects of three-body
      interactions.

PMID- 23004266
TI  - Measurement of the 18Ne(alpha,p0) 21Na reaction cross section in the burning
      energy region for x-ray bursts.
AB  - The 18Ne(alpha,p) 21Na reaction provides one of the main HCNO-breakout routes
      into the rp process in x-ray bursts. The 18Ne(alpha,p0) 21Na reaction cross
      section has been determined for the first time in the Gamow energy region for
      peak temperatures T~2  GK by measuring its time-reversal reaction 21Na(p,alpha)
      18Ne in inverse kinematics. The astrophysical rate for ground-state to ground
      state transitions was found to be a factor of 2 lower than Hauser-Feshbach
      theoretical predictions. Our reduced rate will affect the physical conditions
      under which breakout from the HCNO cycles occurs via the 18Ne(alpha,p) 21Na
      reaction.

PMID- 23004267
TI  - Liquid-state nuclear spin comagnetometers.
AB  - We discuss nuclear spin comagnetometers based on ultralow-field nuclear magnetic
      resonance in mixtures of miscible solvents, each rich in a different nuclear
      spin. In one version thereof, Larmor precession of protons and 19F nuclei in a
      mixture of thermally polarized pentane and hexafluorobenzene is monitored via a
      sensitive alkali-vapor magnetometer. We realize transverse relaxation times in
      excess of 20 s and suppression of magnetic field fluctuations by a factor of
      3400. We estimate it should be possible to achieve single-shot sensitivity of
      about 5*10(-9)  Hz, or about 5*10(-11)  Hz in ~1 day of integration. In a second
      version, spin precession of protons and 129Xe nuclei in a mixture of pentane and
      hyperpolarized liquid xenon is monitored using superconducting quantum
      interference devices. Application to spin-gravity experiments, electric dipole
      moment experiments, and sensitive gyroscopes is discussed.

PMID- 23004269
TI  - Manipulating the annihilation dynamics of positronium via collective radiation.
AB  - A method is investigated to manipulate the annihilation dynamics of a dense gas
      of positronium atoms employing superradiance and subradiance regimes of the
      cooperative spontaneous emission of the system. The corresponding annihilation
      dynamics is explored in two setups with regard to its fundamental novel
      properties and controlled by the gas density and by the intensity of a driving
      strong resonant laser field. In particular, the method allows us to increase the
      annihilation lifetime of an ensemble of positronium atoms by trapping the atoms
      in the excited state via collective radiative effects in the resonant laser
      field. In the second setup, the effect is enhanced by employing a cavity field.
      The maximum lifetime increase is by a factor of about 200 for para-positronium
      and by a factor of about 100 for ortho-positronium.

PMID- 23004268
TI  - First measurement of pure electron shakeoff in the beta decay of trapped 6He+
      ions.
AB  - The electron shakeoff probability of 6Li2+ ions resulting from the beta- decay of
      6He+ ions has been measured with high precision using a specially designed recoil
      ion spectrometer. This is the first measurement of a pure electron shakeoff
      following nuclear beta decay, not affected by multielectron processes such as
      Auger cascades. In this ideal textbook case for the application of the sudden
      approximation, the experimental ionization probability was found to be
      P(so)(exp)=0.02339(36) in perfect agreement with simple quantum mechanical
      calculations.

PMID- 23004270
TI  - Trans-spectral orbital angular momentum transfer via four-wave mixing in Rb
      vapor.
AB  - We report the transfer of phase structure and, in particular, of orbital angular
      momentum from near-infrared pump light to blue light generated in a four-wave
      mixing process in 85Rb vapor. The intensity and phase profile of the two pump
      lasers at 780 and 776 nm, shaped by a spatial light modulator, influences the
      phase and intensity profile of light at 420 nm, which is generated in a
      subsequent coherent cascade. In particular, we observe that the phase profile
      associated with orbital angular momentum is transferred entirely from the pump
      light to the blue. Pumping with more complicated light profiles results in the
      excitation of spatial modes in the blue that depend strongly on phase matching,
      thus demonstrating the parametric nature of the mode transfer. These results have
      implications on the inscription and storage of phase information in atomic gases.

PMID- 23004271
TI  - Field locked to a Fock state by quantum feedback with single photon corrections.
AB  - Fock states with photon numbers n up to 7 are prepared on demand in a microwave
      superconducting cavity by a quantum feedback procedure that reverses decoherence
      induced quantum jumps. Circular Rydberg atoms are used as quantum nondemolition
      sensors or as single-photon emitter or absorber actuators. The quantum nature of
      these actuators matches the correction of single-photon quantum jumps due to
      relaxation. The flexibility of this method is suited to the generation of
      arbitrary sequences of Fock states.

PMID- 23004272
TI  - Waveguiding at the edge of a three-dimensional photonic crystal.
AB  - We find that electromagnetic waves can be guided at the edge of a three
      dimensional photonic crystal in air. When the waveguide is defined by the
      intersection of two surface planes, the edge modes are associated with the
      corresponding surface bands. A simple cell counting approach is presented to
      describe the periodic evolution of the system with interesting interplays among
      edge, surface, and bulk states.

PMID- 23004273
TI  - Channeling chaotic rays into waveguides for efficient collection of microcavity
      emission.
AB  - We demonstrate a robust and generic mechanism, which we term "chaos-assisted
      channeling," to achieve unidirectional output from wave-chaotic microcavities
      with long-lived resonances. It utilizes the coexistence of regular and chaotic
      ray dynamics in most deformed microcavities. Long-lived resonances are formed by
      total internal reflection on classical periodic orbits, and their leakage into
      the chaotic region of the phase space is efficiently channeled into an attached
      waveguide without additional loss. We explain this behavior using a ray dynamics
      analysis which is confirmed via numerical simulations and experimental
      demonstration.

PMID- 23004274
TI  - Photonic nonlinear transient computing with multiple-delay wavelength dynamics.
AB  - We report on the experimental demonstration of a hybrid optoelectronic
      neuromorphic computer based on a complex nonlinear wavelength dynamics including
      multiple delayed feedbacks with randomly defined weights. This neuromorphic
      approach is based on a new paradigm of a brain-inspired computational unit,
      intrinsically differing from Turing machines. This recent paradigm consists in
      expanding the input information to be processed into a higher dimensional phase
      space, through the nonlinear transient response of a complex dynamics excited by
      the input information. The computed output is then extracted via a linear
      separation of the transient trajectory in the complex phase space. The hyperplane
      separation is derived from a learning phase consisting of the resolution of a
      regression problem. The processing capability originates from the nonlinear
      transient, resulting in nonlinear transient computing. The computational
      performance is successfully evaluated on a standard benchmark test, namely, a
      spoken digit recognition task.

PMID- 23004275
TI  - Self-affine elastic contacts: percolation and leakage.
AB  - We study fluid flow at the interfaces between elastic solids with randomly rough,
      self-affine surfaces. We show by numerical simulation that elastic deformation
      lowers the relative contact area at which contact patches percolate in comparison
      to traditional approaches to seals. Elastic deformation also suppresses leakage
      through contacts even far away from the percolation threshold. Reliable estimates
      for leakage can be obtained by combining Persson's contact mechanics theory with
      a slightly modified version of Bruggeman's effective-medium solution of the
      Reynolds equation.

PMID- 23004276
TI  - Experimental evidence for a transient Tayler instability in a cylindrical liquid
      metal column.
AB  - In the current-driven, kink-type Tayler instability (TI) a sufficiently strong
      azimuthal magnetic field becomes unstable against nonaxisymmetric perturbations.
      The TI has been discussed as a possible ingredient of the solar dynamo mechanism
      and a source of the helical structures in cosmic jets. It is also considered as a
      size-limiting factor for liquid metal batteries. We report on a liquid metal TI
      experiment using a cylindrical column of the eutectic alloy GaInSn to which
      electrical currents of up to 8 kA are applied. We present results of external
      magnetic field measurements that indicate the transient occurrence of the TI in
      good agreement with numerical predictions. The interference of TI with the
      competing large-scale convection, resulting from Joule heating, is also
      discussed.

PMID- 23004277
TI  - Covariant statistical mechanics and the stress-energy tensor.
AB  - After recapitulating the covariant formalism of equilibrium statistical mechanics
      in special relativity and extending it to the case of a nonvanishing spin tensor,
      we show that the relativistic stress-energy tensor at thermodynamical equilibrium
      can be obtained from a functional derivative of the partition function with
      respect to the inverse temperature four-vector beta. For usual thermodynamical
      equilibrium, the stress-energy tensor turns out to be the derivative of the
      relativistic thermodynamic potential current with respect to the four-vector
      beta, i.e., T(MUnu)=-?Phi(MU)/?beta(nu). This formula establishes a relation
      between the stress-energy tensor and the entropy current at equilibrium, possibly
      extendable to nonequilibrium hydrodynamics.

PMID- 23004278
TI  - Energy constrained transport maximization across a fluid interface.
AB  - With enhancing mixing in micro- or nanofluidic applications in mind, the problem
      of maximizing fluid transport across a fluid interface subject to an available
      energy budget is examined. The optimum cross-interface perturbing velocity is
      obtained explicitly in the time-periodic instance using an Euler-Lagrange
      constrained optimization approach. Numerical investigations which calculate
      transferred lobe areas and cross-interface flux are used to verify that the
      predicted strategy achieves optimum transport. Explicit active protocols for
      achieving this optimal transport are suggested.

PMID- 23004279
TI  - Dielectric wakefield acceleration of a relativistic electron beam in a slab
      symmetric dielectric lined waveguide.
AB  - We report first evidence of wakefield acceleration of a relativistic electron
      beam in a dielectric-lined slab-symmetric structure. The high energy tail of a
      ~60  MeV electron beam was accelerated by ~150  keV in a 2 cm-long, slab
      symmetric SiO2 waveguide, with the acceleration or deceleration clearly visible
      due to the use of a beam with a bifurcated longitudinal distribution that serves
      to approximate a driver-witness beam pair. This split-bunch distribution is
      verified by longitudinal reconstruction analysis of the emitted coherent
      transition radiation. The dielectric waveguide structure is further characterized
      by spectral analysis of the emitted coherent Cherenkov radiation at THz
      frequencies, from a single electron bunch, and from a relativistic bunch train
      with spacing selectively tuned to the second longitudinal mode (TM02). Start-to
      end simulation results reproduce aspects of the electron beam bifurcation
      dynamics, emitted THz radiation properties, and the observation of acceleration
      in the dielectric-lined, slab-symmetric waveguide.

PMID- 23004280
TI  - Frequency-resolved nonlinear turbulent energy transfer into zonal flows in
      strongly heated L-mode plasmas in the HL-2A tokamak.
AB  - The absolute rate of nonlinear energy transfer among broadband turbulence, low
      frequency zonal flows (ZFs) and geodesic acoustic modes (GAMs) was measured for
      the first time in fusion-grade plasmas using two independent methods across a
      range of heating powers. The results show that turbulent kinetic energy from
      intermediate frequencies (20-80 kHz) was transferred into ZFs and GAMs, as well
      as into fluctuations at higher frequencies (>80  kHz). As the heating power was
      increased, the energy transfer from turbulence into GAMs and the GAM amplitudes
      increased, peaked and then decreased, while the energy transfer into the ZFs and
      the ZFs themselves increased monotonically with heating power. Thus there exists
      a competition between ZFs and GAMs for the transfer of turbulent energy, and the
      transfer into ZFs becomes dominant as the heating power is increased. The
      poloidal-radial Reynolds stress and the mean radial electric field profiles were
      also measured at different heating powers and found to be consistent with the
      energy transfer measurement. The results suggest that ZFs play an important role
      in the low-to-high (L-H) plasma confinement transition.

PMID- 23004281
TI  - Resilience of quasi-isodynamic stellarators against trapped-particle
      instabilities.
AB  - It is shown that in perfectly quasi-isodynamic stellarators, trapped particles
      with a bounce frequency much higher than the frequency of the instability are
      stabilizing in the electrostatic and collisionless limit. The collisionless
      trapped-particle instability is therefore stable as well as the ordinary electron
      density-gradient-driven trapped-electron mode. This result follows from the
      energy balance of electrostatic instabilities and is thus independent of all
      other details of the magnetic geometry.

PMID- 23004282
TI  - Pedestal structure model.
AB  - Predictions are developed for gradients and profiles of the electron density and
      temperature in tokamak H-mode pedestals that are in transport quasiequilibrium.
      They are based on assuming paleoclassical processes provide the irreducible
      minimum radial plasma transport and dominate in the steep gradient regions of
      pedestals. The predictions agree (within a factor of about two) with properties
      of a number of pedestal experimental results.

PMID- 23004283
TI  - Self-organized bursts of coherent stimulated Raman scattering and hot electron
      transport in speckled laser plasma media.
AB  - Nonlinear electron trapping physics governs the onset and saturation of
      stimulated Raman scattering (SRS) in laser beams with many speckles. Hot
      electrons from intense speckles, produced during SRS daughter electron-plasma
      wave bowing and filamentation, seed and enhance the growth of SRS in neighboring
      speckles by reducing Landau damping. Trapping-induced nonlinearity and speckle
      interaction through transport of hot electrons and back- and sidescattered SRS
      waves enable the system of speckles to self-organize and exhibit coherent, sub-ps
      SRS bursts with more than 100% instantaneous reflectivity, consistent with a SRS
      transverse coherence width much larger than a speckle width.

PMID- 23004284
TI  - Nanoplasma dynamics of single large xenon clusters irradiated with superintense x
      ray pulses from the linac coherent light source free-electron laser.
AB  - The plasma dynamics of single mesoscopic Xe particles irradiated with intense
      femtosecond x-ray pulses exceeding 10(16)  W/cm2 from the Linac Coherent Light
      Source free-electron laser are investigated. Simultaneous recording of
      diffraction patterns and ion spectra allows eliminating the influence of the
      laser focal volume intensity and particle size distribution. The data show that
      for clusters illuminated with intense x-ray pulses, highly charged ionization
      fragments in a narrow distribution are created and that the nanoplasma
      recombination is efficiently suppressed.

PMID- 23004285
TI  - Pair density waves and vortices in an elongated spin-1/2 Fermi gas.
AB  - We study the vortex structures of a (pseudo)spin-1/2 Fermi gas experiencing a
      uniform effective magnetic field in an anisotropic trap that interpolates between
      quasi-one dimensional (1D) and quasi-two dimensional (2D). At a fixed chemical
      potential, reducing the anisotropy (or equivalently increasing the attractive
      interactions or increasing the magnetic field) leads to instabilities towards
      pair density waves and vortex lattices. Reducing the chemical potential
      stabilizes the system. We calculate the phase diagram and explore the density and
      pair density. The structures are similar to those predicted for superfluid Bose
      gases. We further calculate the paired fraction, showing how it depends on the
      chemical potential and anisotropy.

PMID- 23004286
TI  - Short-time spin dynamics in strongly correlated few-fermion systems.
AB  - The nonequilibrium spin dynamics of a one-dimensional system of repulsively
      interacting fermions is studied by means of density-matrix renormalization group
      simulations. We focus on the short-time decay of the oscillation amplitudes of
      the centers of mass of spin-up and spin-down fermions. Because of many body
      effects, the decay is found to evolve from quadratic to linear in time, and
      eventually back to quadratic as the strength of the interaction increases. The
      characteristic rate of the decay increases linearly with the strength of
      repulsion in the weak-coupling regime, while it is inversely proportional to it
      in the strong-coupling regime. Our predictions can be tested in experiments on
      tunable ultracold few-fermion systems in one-dimensional traps.

PMID- 23004287
TI  - Inhomogeneous spin diffusion in traps with cold atoms.
AB  - The spin diffusion and damped oscillations are studied in the collision of two
      spin polarized clouds of cold atoms with resonant interactions. The strong
      density dependence of the diffusion coefficient leads to inhomogeneous spin
      diffusion that changes from central to surface spin flow as the temperature
      increases. The inhomogeneity and the smaller finite trap size significantly
      reduce the spin diffusion rate at low temperatures. The resulting spin diffusion
      rates and spin drag at longer time scales are compatible with measurements at low
      to high temperatures for resonant attractive interactions but are incompatible
      with a metastable ferromagnetic phase. This does not exclude that the colliding
      clouds can evolve into a repulsive initial state which subsequently decays during
      the bounce and the initial damped oscillations.

PMID- 23004288
TI  - Experimental evidence for epitaxial silicene on diboride thin films.
AB  - As the Si counterpart of graphene, silicene may be defined as an at least
      partially sp2-hybridized, atom-thick honeycomb layer of Si that possesses pi
      electronic bands. Here we show that two-dimensional, epitaxial silicene forms
      through surface segregation on zirconium diboride thin films grown on Si wafers.
      A particular buckling of silicene induced by the epitaxial relationship with the
      diboride surface leads to a direct pi-electronic band gap at the Gamma point.
      These results demonstrate that the buckling and thus the electronic properties of
      silicene are modified by epitaxial strain.

PMID- 23004289
TI  - Determination of the ground-state atomic structures of size-selected au
      nanoclusters by electron-beam-induced transformation.
AB  - The equilibrium ground state atomic structures of nanoparticles are critical to
      understanding the relationship between their structure and functionality, e.g.,
      in catalysis, and are the standard output of first principles and semiempirical
      theoretical treatments. We demonstrate a method of obtaining a stable population
      of the structural isomers of supported Au clusters from a metastable initial
      array via electron beam irradiation. Statistical investigation of size-selected
      Au clusters containing 923+/-23 atoms via aberration-corrected scanning
      transmission electron microscopy shows that virtually all of the icosahedral (Ih)
      clusters undergo structural transformations into decahedral (Dh) (primarily) or
      fcc isomers while Dh and FCC clusters generally retain their atomic structures
      after electron irradiation of each cluster individually for up to 400 s at a dose
      of 2.4*10(4)  e-/angstrom2/frame. Intermediate phases are often observed in the
      image series (videos) before the appearance of the new stable isomers, the
      relative structural populations of which can be controlled via the electron beam
      dose. The comprehensive results reported here should provide a valuable
      experimental reference for testing or refining potential models and for kinetic
      or dynamical treatments of the atomic configurations.

PMID- 23004290
TI  - Melt-growth dynamics in CdTe crystals.
AB  - We use a new, quantum-mechanics-based bond-order potential (BOP) to reveal melt
      growth dynamics and fine scale defect formation mechanisms in CdTe crystals.
      Previous molecular dynamics simulations of semiconductors have shown
      qualitatively incorrect behavior due to the lack of an interatomic potential
      capable of predicting both crystalline growth and property trends of many
      transitional structures encountered during the melt->crystal transformation.
      Here, we demonstrate successful molecular dynamics simulations of melt growth in
      CdTe using a BOP that significantly improves over other potentials on property
      trends of different phases. Our simulations result in a detailed understanding of
      defect formation during the melt growth process. Equally important, we show that
      the new BOP enables defect formation mechanisms to be studied at a scale level
      comparable to empirical molecular dynamics simulation methods with a fidelity
      level approaching quantum-mechanical methods.

PMID- 23004291
TI  - Nonequilibrium cluster diffusion during growth and evaporation in two dimensions.
AB  - The diffusion of growing or evaporating two-dimensional clusters is investigated.
      At equilibrium, it is well known that the mean square displacement (MSD) of the
      cluster center of mass is linear in time. In nonequilibrium conditions, we find
      that the MSD exhibits a nonlinear time dependence, leading to three regimes: (i)
      during curvature-driven evaporation, the MSD shows a square-root singularity
      close to the collapse time; (ii) in slow growth or evaporation, the dynamics is
      in the Edwards-Wilkinson universality class, and the MSD shows a logarithmic
      behavior; (iii) far from equilibrium, the dynamics belongs to the Kardar-Parisi
      Zhang universality class and the MSD shows a power-law behavior with a
      characteristic exponent 1/3. These results agree with kinetic Monte Carlo
      simulations, and can be generalized to other universality classes.

PMID- 23004292
TI  - Efficient defect healing in catalytic carbon nanotube growth.
AB  - The energetics of topological defects (TDs) in carbon nanotubes (CNTs) and their
      kinetic healing during the catalytic growth are explored theoretically. Our study
      indicates that, with the assistance of a metal catalyst, TDs formed during the
      addition of C atoms can be efficiently healed at the CNT-catalyst interface.
      Theoretically, a TD-free CNT wall with 10(8)-10(11) carbon atoms is achievable,
      and, as a consequence, the growth of perfect CNTs up to 0.1-100 cm long is
      possible since the linear density of a CNT is ~100 carbon atoms per nanometer. In
      addition, the calculation shows that, among catalysts most often used, Fe has the
      highest efficiency for defect healing.

PMID- 23004293
TI  - Capillary emptying and short-range wetting.
AB  - We consider a liquid trapped in a narrow horizontal capillary, under the
      influence of gravity. As the slit is widened, the meniscus, separating the
      capillary liquid from gas, deforms and develops a long tongue extending along the
      bottom wall. As a critical slit width is approached, the length of the tongue
      diverges continuously, leading to the emptying of the capillary. We show that the
      critical singularities characterizing emptying are the same as those at short
      ranged wetting transitions, but at a scale set by the capillary length rather
      than the bulk correlation length. These meso- or macroscopic versions of both
      complete and critical wetting are observable in the laboratory and are studied
      here using a colloid-polymer mixture.

PMID- 23004294
TI  - Improvement of scanning tunneling microscopy resolution with H-sensitized tips.
AB  - Recent scanning tunneling hydrogen microscopy (STHM) experiments on PTCDA
      (perylene-3,4,9,10-tetracarboxylic-3,4,9,10-dianhydride)/Au(111) have shown
      unprecedented intramolecular and intermolecular spatial resolution. The origin of
      this resolution is studied using an accurate STHM theoretical simulation
      technique that includes a detailed description of the electronic structure of
      both the tip and sample. Our results show that H2 molecules are dissociated on
      the Au tip; the adsorbed H atoms change the density of states at the Fermi level
      (E(F)) of the tip, increasing its p-orbital character and reducing the s-orbital
      contribution. Also, due to the interaction with the H-decorated tip, E(F) is
      shifted to the middle of the PTCDA lowest unoccupied molecular orbital peak,
      increasing dramatically the density of states of the sample at E(F). These
      effects give rise to the enhanced STHM resolution.

PMID- 23004295
TI  - Raman spectroscopy study of rotated double-layer graphene: misorientation-angle
      dependence of electronic structure.
AB  - We present a systematic Raman study of unconventionally stacked double-layer
      graphene, and find that the spectrum strongly depends on the relative rotation
      angle between layers. Rotation-dependent trends in the position, width and
      intensity of graphene 2D and G peaks are experimentally established and accounted
      for theoretically. Our theoretical analysis reveals that changes in electronic
      band structure due to the interlayer interaction, such as rotational-angle
      dependent Van Hove singularities, are responsible for the observed spectral
      features. Our combined experimental and theoretical study provides a deeper
      understanding of the electronic band structure of rotated double-layer graphene,
      and leads to a practical way to identify and analyze rotation angles of
      misoriented double-layer graphene.

PMID- 23004296
TI  - Origin of doping in quasi-free-standing graphene on silicon carbide.
AB  - We explain the robust p-type doping observed for quasi-free-standing graphene on
      hexagonal silicon carbide by the spontaneous polarization of the substrate. This
      mechanism is based on a bulk property of SiC, unavoidable for any hexagonal
      polytype of the material and independent of any details of the interface
      formation. We show that sign and magnitude of the polarization are in perfect
      agreement with the doping level observed in the graphene layer. With this
      mechanism, models based on hypothetical acceptor-type defects as they are
      discussed so far are obsolete. The n-type doping of epitaxial graphene is
      explained conventionally by donorlike states associated with the buffer layer and
      its interface to the substrate that overcompensate the polarization doping.

PMID- 23004297
TI  - Kondo screening and magnetism at interfaces.
AB  - The nature of magnetic order and transport properties near surfaces is a topic of
      great current interest. Here we model metal-insulator interfaces with a
      multilayer system governed by a tight-binding Hamiltonian in which the
      interaction is nonzero on one set of adjacent planes and zero on another. As the
      interface hybridization is tuned, magnetic and metallic properties undergo an
      evolution that reflects the competition between antiferromagnetism and (Kondo)
      singlet formation in a scenario similar to that occurring in heavy-fermion
      materials. For a few-layer system at intermediate hybridization, a Kondo
      insulating phase results, where magnetic order and conductivity are suppressed in
      all layers. As more insulating layers are added, magnetic order is restored in
      all correlated layers except that at the interface. Residual signs of Kondo
      physics are however evident in the bulk as a substantial reduction of the order
      parameter in the 2 to 3 layers immediately adjacent to the interfacial one. We
      find no signature of long-range magnetic order in the metallic layers.

PMID- 23004298
TI  - Kondo metal and ferrimagnetic insulator on the triangular kagome lattice.
AB  - We obtain the rich phase diagrams in the Hubbard model on the triangular kagome
      lattice as a function of interaction, temperature, and asymmetry by combining the
      cellular dynamical mean-field theory with the continuous time quantum Monte Carlo
      method. The phase diagrams show the asymmetry separates the critical points in
      the Mott transition of two sublattices on the triangular kagome lattice and
      produces two novel phases called plaquette insulator with a clearly visible gap
      and a gapless Kondo metal. When the Coulomb interaction is stronger than the
      critical value U(c), a short range paramagnetic insulating state, which is a
      candidate for the short rang resonating valence-bond spin liquid, emerges before
      the ferrimagnetic order is formed independent of asymmetry. Furthermore, we
      discuss how to measure these phases in future experiments.

PMID- 23004299
TI  - Observation of the hybridization gap and Fano resonance in the Kondo lattice
      URu2Si2.
AB  - The nature of the second-order phase transition that occurs in URu2Si2 at 17.5 K
      remains puzzling despite intensive research. A key question emerging in the field
      is whether a hybridization gap between the renormalized bands can be identified
      as the "hidden" order parameter. We report on the measurement of a hybridization
      gap in URu2Si2 employing a spectroscopic technique based on quasiparticle
      scattering. The differential conductance exhibits an asymmetric double-peak
      structure, a clear signature for a Fano resonance in a Kondo lattice. The
      hybridization gap opens well above 17.5 K, indicating that it is not the hidden
      order parameter. Our results put stringent constraints on the origin of the
      hidden order transition in URu2Si2 and demonstrate that quasiparticle scattering
      spectroscopy can probe the band renormalizations in a Kondo lattice via detection
      of a novel type of Fano resonance.

PMID- 23004300
TI  - Floating electron states in covalent semiconductors.
AB  - We report first-principles electronic-structure calculations that clarify the
      floating nature of electron states in covalent semiconductors. It is found that
      wave functions of several conduction- and valence-band states, including the
      conduction-band minima, do not distribute near atomic sites, as was taken for
      granted, but float in interstitial channels in most semiconductors. The
      directions and shapes of the interstitial channels depend on the crystal symmetry
      so that mysterious variation of the energy gaps in SiC polymorphs is naturally
      explained by considering the floating nature.

PMID- 23004301
TI  - Electronic pumping of quasiequilibrium Bose-Einstein-condensed magnons.
AB  - We theoretically investigate spin transfer between a system of quasiequilibrated
      Bose-Einstein-condensed magnons in an insulator in direct contact with a
      conductor. While charge transfer is prohibited across the interface, spin
      transport arises from the exchange coupling between insulator and conductor
      spins. In a normal insulator phase, spin transport is governed solely by the
      presence of thermal and spin-diffusive gradients; the presence of Bose-Einstein
      condensation (BEC), meanwhile, gives rise to a temperature-independent condensate
      spin current. Depending on the thermodynamic bias of the system, spin may flow in
      either direction across the interface, engendering the possibility of a dynamical
      phase transition of magnons. We discuss the experimental feasibility of observing
      a BEC steady state (fomented by a spin Seebeck effect), which is contrasted to
      the more familiar spin-transfer-induced classical instabilities.

PMID- 23004302
TI  - Theory of spin relaxation in two-electron lateral coupled quantum dots.
AB  - A global quantitative picture of the phonon-induced two-electron spin relaxation
      in GaAs double quantum dots is presented using highly accurate numerics. Wide
      regimes of interdot coupling, magnetic field magnitude and orientation, and
      detuning are explored in the presence of a nuclear bath. Most important, the
      giant magnetic anisotropy of the singlet-triplet relaxation can be controlled by
      detuning switching the principal anisotropy axes: a protected state becomes
      unprotected upon detuning and vice versa. It is also established that nuclear
      spins can dominate spin relaxation for unpolarized triplets even at high magnetic
      fields, contrary to common belief.

PMID- 23004303
TI  - Fluctuation relations for spintronics.
AB  - Fluctuation relations are derived in systems where the spin degree of freedom and
      magnetic interactions play a crucial role. The form of the nonequilibrium
      fluctuation theorems relies on the assumption of a local balance condition. We
      demonstrate that in some cases the presence of magnetic interactions violates
      this condition. Nevertheless, fluctuation relations can be obtained from the
      microreversibility principle sustained only at equilibrium as a symmetry of the
      cumulant generating function for spin currents. We illustrate the spintronic
      fluctuation relations for a quantum dot coupled to partially polarized helical
      edge states.

PMID- 23004304
TI  - Simultaneous control of ionic and electronic conductivity in materials: thallium
      bromide case study.
AB  - Achieving simultaneous control of ionic and electronic conductivity in materials
      is one of the great challenges in solid state ionics. Since these properties are
      intertwined, optimizing one often results in degrading the other. In this Letter,
      we propose a method to limit ionic current without impacting the electronic
      properties of a general class of materials, based on codoping with oppositely
      charged ions. We describe a set of analyses, based on parameter-free quantum
      mechanical simulations, to assess the efficacy of the approach and determine
      optimal dopants. For illustration, we discuss the case of thallium bromide, a
      wide band gap ionic crystal whose promise as a room-temperature radiation
      detector has been hampered by ionic migration. We find that acceptors and donors
      bind strongly with the charged vacancies that mediate ionic transport, forming
      neutral complexes that render them immobile. Analysis of carrier recombination
      and scattering by the complexes allows the identification of specific dopants
      that do not degrade electronic transport in the crystal.

PMID- 23004305
TI  - Direct observation of photoinduced bound charge-pair states at an organic
      inorganic semiconductor interface.
AB  - It is generally considered that photoinduced charge transfer at the organic
      inorganic interfaces in hybrid photovoltaic devices immediately results in a pair
      of free charge carriers. We extend a novel interface-selective ultrafast "optical
      pump-push photocurrent probe" technique to study hybrid photovoltaic systems and
      observe bound electron-hole pair states at the organic-inorganic interface formed
      between electron-accepting zinc oxide and electron-donating conjugated polymers.
      We estimate that ~50% of photogenerated charges stay bound and later recombine,
      thus hindering the photovoltaic performance of polymer/ZnO cells. We further
      demonstrate that interface modification with a fullerene derivative decreases the
      fraction of bound charges to ~25%, which substantially improves the device
      efficiency.

PMID- 23004306
TI  - Imaging fractional incompressible stripes in integer quantum Hall systems.
AB  - Transport experiments provide conflicting evidence on the possible existence of
      fractional order within integer quantum Hall systems. In fact, integer edge
      states sometimes behave as monolithic objects with no inner structure, while
      other experiments clearly highlight the role of fractional substructures.
      Recently developed low-temperature scanning probe techniques offer today an
      opportunity for a deeper-than-ever investigation of spatial features of such edge
      systems. Here we use scanning-gate microscopy and demonstrate that fractional
      features were unambiguously observed in every integer quantum Hall constriction
      studied. We present also an experimental estimate of the width of the fractional
      incompressible stripes corresponding to filling factors 1/3, 2/5, 3/5, and 2/3.
      Our results compare well with predictions of the edge-reconstruction theory.

PMID- 23004307
TI  - Ideal two-dimensional electron systems with a giant Rashba-type spin splitting in
      real materials: surfaces of bismuth tellurohalides.
AB  - Spintronics is aimed at actively controlling and manipulating the spin degrees of
      freedom in semiconductor devices. A promising way to achieve this goal is to make
      use of the tunable Rashba effect that relies on the spin-orbit interaction in a
      two-dimensional electron system immersed in an inversion-asymmetric environment.
      The spin-orbit-induced spin splitting of the two-dimensional electron state
      provides a basis for many theoretically proposed spintronic devices. However, the
      lack of semiconductors with large Rashba effect hinders realization of these
      devices in actual practice. Here we report on a giant Rashba-type spin splitting
      in two-dimensional electron systems that reside at tellurium-terminated surfaces
      of bismuth tellurohalides. Among these semiconductors, BiTeCl stands out for its
      isotropic metallic surface-state band with the Gamma-point energy lying deep
      inside the bulk band gap. The giant spin splitting of this band ensures a
      substantial spin asymmetry of the inelastic mean free path of quasiparticles with
      different spin orientations.

PMID- 23004308
TI  - Electron-electron interactions in artificial graphene.
AB  - Recent advances in the creation and modulation of graphenelike systems are
      introducing a science of "designer Dirac materials". In its original definition,
      artificial graphene is a man-made nanostructure that consists of identical
      potential wells (quantum dots) arranged in an adjustable honeycomb lattice in the
      two-dimensional electron gas. As our ability to control the quality of artificial
      graphene samples improves, so grows the need for an accurate theory of its
      electronic properties, including the effects of electron-electron interactions.
      Here we determine those effects on the band structure and on the emergence of
      Dirac points.

PMID- 23004309
TI  - Modeling flux noise in SQUIDs due to hyperfine interactions.
AB  - Recent experiments implicate spins on the surface of metals as the source of flux
      noise in superconducting quantum interference devices and indicate that these
      spins are able to relax without conserving total magnetization. We present a
      model of 1/f flux noise in which electron spins on the surface of metals can
      relax via hyperfine interactions. Our results indicate that flux noise would be
      significantly reduced in superconducting materials where the most abundant
      isotopes do not have nuclear moments, such as zinc and lead.

PMID- 23004310
TI  - Coexistence and competition of the short-range incommensurate antiferromagnetic
      order with the superconducting state of BaFe(2-x)Ni(x)As2.
AB  - Superconductivity in the iron pnictides develops near antiferromagnetism, and the
      antiferromagnetic (AF) phase appears to overlap with the superconducting phase in
      some materials such as BaFe(2-x)T(x)As2 (where T=Co or Ni). Here we use neutron
      scattering to demonstrate that genuine long-range AF order and superconductivity
      do not coexist in BaFe(2-x)Ni(x)As2 near optimal superconductivity. In addition,
      we find a first-order-like AF-to-superconductivity phase transition with no
      evidence for a magnetic quantum critical point. Instead, the data reveal that
      incommensurate short-range AF order coexists and competes with superconductivity,
      where the AF spin correlation length is comparable to the superconducting
      coherence length.

PMID- 23004311
TI  - Interpocket pairing and gap symmetry in Fe-based superconductors with only
      electron pockets.
AB  - We analyze the pairing symmetry in Fe-based superconductors AFe2Se2 (A=K, Rb, Cs)
      which contain only electron pockets. We argue that the pairing condensate in such
      systems contains not only intrapocket component but also interpocket component,
      made of fermions belonging to different electron pockets. We analyze the
      interplay between intrapocket and interpocket pairing, depending on the
      ellipticity of electron pockets and the strength of their hybridization. We show
      that with increasing hybridization, the system undergoes a transition from a d
      wave state to an s+- state, in which the gap changes sign between hybridized
      pockets. This s+- state has the full gap and at the same time supports spin
      resonance, in agreement with the data. Near the boundary between d and s+-
      states, we found a long-sought s+id state which breaks time-reversal symmetry.

PMID- 23004312
TI  - Two-dimensional superconducting phase in LaTiO3/SrTiO3 heterostructures induced
      by high-mobility carrier doping.
AB  - In this Letter, we show that a superconducting two-dimensional electron gas is
      formed at the LaTiO3/SrTiO3 interface whose transition temperature can be
      modulated by a back-gate voltage. The gas consists of two types of carriers: a
      majority of low-mobility carriers always present, and a few high-mobility ones
      that can be injected by electrostatic doping. The calculation of the electron
      spatial distribution in the confinement potential shows that the high-mobility
      electrons responsible for superconductivity set at the edge of the gas whose
      extension can be tuned by the field effect.

PMID- 23004313
TI  - Domain-wall dynamics in translationally nonivariant nanowires: theory and
      applications.
AB  - We generalize domain-wall dynamics to the case of translationally noninvariant
      ferromagnetic nanowires. The obtained equations of motion make the description of
      the domain-wall propagation more realistic by accounting for the variations along
      the wire, such as disorder or change in the wire shape. We show that the
      effective equations of motion are very general and do not depend on the model
      details. As an example of their use, we consider an hourglass-shaped nanostrip in
      detail. A transverse domain wall is trapped in the middle and has two stable
      magnetization directions. We study the switching between the two directions by
      short current pulses. We obtain the exact time dependence of the current pulses
      required to switch the magnetization with the minimal Ohmic losses per switching.
      Furthermore, we find how the Ohmic losses per switching depend on the switching
      time for the optimal current pulse. As a result, we show that as a magnetic
      memory device this nanodevice may be 10(5) times more energy efficient than the
      best modern devices.

PMID- 23004314
TI  - Direct observation of massless domain wall dynamics in nanostripes with
      perpendicular magnetic anisotropy.
AB  - Domain wall motion induced by nanosecond current pulses in nanostripes with
      perpendicular magnetic anisotropy (Pt/Co/AlO(x)) is shown to exhibit negligible
      inertia. Time-resolved magnetic microscopy during current pulses reveals that the
      domain walls start moving, with a constant speed, as soon as the current reaches
      a constant amplitude, and no or little motion takes place after the end of the
      pulse. The very low "mass" of these domain walls is attributed to the combination
      of their narrow width and high damping parameter alpha. Such a small inertia
      should allow accurate control of domain wall motion by tuning the duration and
      amplitude of the current pulses.

PMID- 23004315
TI  - Spin textures in strongly coupled electron spin and magnetic or nuclear spin
      systems in quantum dots.
AB  - Controlling electron spins strongly coupled to magnetic and nuclear spins in
      solid state systems is an important challenge in the field of spintronics and
      quantum computation. We show here that electron droplets with no net spin in
      semiconductor quantum dots strongly coupled with magnetic ion or nuclear spin
      systems break down at low temperature and form a nontrivial antiferromagnetic
      spatially ordered spin texture of magnetopolarons. The spatially ordered combined
      electron-magnetic ion spin texture, associated with spontaneous symmetry breaking
      in the parity of electronic charge and spin densities and magnetization of
      magnetic ions, emerges from an ab initio density functional approach to the
      electronic system coupled with mean-field approximation for the magnetic or
      nuclear spin system. The predicted phase diagram determines the critical
      temperature as a function of coupling strength and identifies possible phases of
      the strongly coupled spin system. The prediction may arrest fluctuations in the
      spin system and open the way to control, manipulate, and prepare magnetic and
      nuclear spin ensembles in semiconductor nanostructures.

PMID- 23004316
TI  - Noncollinear magnetism and spin-orbit coupling in 5d pyrochlore oxide Cd2Os2O7.
AB  - We investigate the electronic and magnetic properties of the pyrochlore oxide
      Cd2Os2O7 using the density-functional theory plus on-site repulsion (U) method,
      and depict the ground-state phase diagram with respect to U. We conclude that the
      all-in-all-out noncollinear magnetic order is stable in a wide range of U. We
      also show that the easy-axis anisotropy arising from the spin-orbit coupling
      plays a significant role in stabilizing the all-in-all-out magnetic order. A
      pseudogap was observed near the transition between the antiferromagnetic metallic
      and insulating phases. Finally, we discuss possible origins of the peculiar low
      temperature (T) properties observed in experiments.

PMID- 23004317
TI  - Tetrahedral magnetic order and the metal-insulator transition in the pyrochlore
      lattice of Cd2Os2O7.
AB  - Cd2Os2O7 shows a peculiar metal-insulator transition at 227 K with magnetic
      ordering in a frustrated pyrochlore lattice, but its magnetic structure in the
      ordered state and the transition origin are yet uncovered. We observed a
      commensurate magnetic peak by resonant x-ray scattering in a high-quality single
      crystal. X-ray diffraction and Raman scattering experiments confirmed that the
      transition is not accompanied with any spatial symmetry breaking. We propose a
      noncollinear all-in-all-out spin arrangement on the tetrahedral network made of
      Os atoms. Based on this we suggest that the transition is not caused by the
      Slater mechanism as believed earlier but by an alternative mechanism related to
      the formation of the specific tetrahedral magnetic order on the pyrochlore
      lattice in the presence of strong spin-orbit interactions.

PMID- 23004318
TI  - Exact spin liquid ground states of the quantum dimer model on the square and
      honeycomb lattices.
AB  - We study a generalized quantum hard-core dimer model on the square and honeycomb
      lattices, allowing for first and second neighbor dimers. At generalized Rokhsar
      Kivelson points, the exact ground states can be constructed, and ground-state
      correlation functions can be equated to those of interacting (1+1)-dimensional
      Grassmann fields. When the concentration of second neighbor dimers is small, the
      ground-state correlations are shown to be short ranged corresponding to a (gaped)
      spin liquid phase. On a 2-torus, the ground states exhibit fourfold topological
      degeneracy. On a finite cylinder we have found a dramatic even-odd effect
      depending on the circumference and propose that this can be used as a numerical
      diagnostic of gapped spin-liquid phases, more generally.

PMID- 23004319
TI  - THz switching of antiferromagnets and ferrimagnets.
AB  - Using analytical calculations as well as computer simulations, we show that
      antiferromagnets can be switched on a time scale of picoseconds using THz laser
      pulses only. This all-optically triggered switching mechanism rests on the
      coordinated dynamics of the two interacting sublattices with an inertial
      character. We calculate the resonance frequencies in the nonlinear regime, the
      orbits, and estimate the field strength required for switching analytically.
      Furthermore, we demonstrate that ferrimagnets can be switched similarly at their
      compensation point.

PMID- 23004320
TI  - Mechanisms of enhanced orbital dia- and paramagnetism: application to the Rashba
      semiconductor BiTeI.
AB  - We study the magnetic susceptibility of a layered semiconductor BiTeI with giant
      Rashba spin splitting both theoretically and experimentally to explore its
      orbital magnetism. Apart from the core contributions, a large temperature
      dependent diamagnetic susceptibility is observed when the Fermi energy E(F) is
      near the crossing point of the Rashba spin-split conduction bands at the time
      reversal symmetry point A. On the other hand, when E(F) is below this band
      crossing, the susceptibility turns to be paramagnetic. These features are
      consistent with first-principles calculations, which also predict an enhanced
      orbital magnetic susceptibility with both positive and negative signs as a
      function of E(F) due to band (anti)crossings. Based on these observations, we
      propose two mechanisms for the enhanced paramagnetic orbital susceptibility.

PMID- 23004321
TI  - Hourglass dispersion in overdoped single-layered manganites.
AB  - The incommensurate stripelike magnetic ordering in two single-layered manganites,
      Nd0.33Sr1.67MnO4 and Pr0.33Ca1.67MnO4, is found to exhibit an hourglasslike
      excitation spectrum very similar to that seen in various cuprates
      superconductors, but only for sufficiently short correlation lengths. Several
      characteristic features of an hourglass dispersion can be identified: enhancement
      of intensity at the merging of the incommensurate branches, rotation of the
      intensity maxima with higher energy transfer, and suppression of the outward
      dispersing branches at low energy. The correlation length of the magnetic
      ordering and the large ratio of intra- to interstripe couplings are identified as
      the decisive parameters causing the hourglass shape of the spectrum.

PMID- 23004322
TI  - Quantum strings in quantum spin ice.
AB  - We study quantum spin ice in an external magnetic field applied along a <100>
      direction. When quantum spin fluctuations are weak, elementary excitations are
      quantum strings with monopoles at their ends manifested as multiple spin wave
      branches in the dynamical structure factor. Strong quantum fluctuations make the
      string tension negative and give rise to the deconfinement of monopoles. We
      discuss our results in the light of recent neutron scattering experiments in
      Yb2Ti2O7.

PMID- 23004323
TI  - Magnetoelectric coupling in single crystal Cu2OSeO3 studied by a novel electron
      spin resonance technique.
AB  - The magnetoelectric (ME) coupling on spin-wave resonances in single-crystal
      Cu2OSeO3 was studied by a novel technique using electron spin resonance combined
      with electric field modulation. An external electric field E induces a magnetic
      field component MU0H(i)=gammaE along the applied magnetic field H with
      gamma=0.7(1)  MUT/(V/mm) at 10 K. The ME coupling strength gamma is found to be
      temperature dependent and highly anisotropic. gamma(T) nearly follows that of the
      spin susceptibility J(M)(T) and rapidly decreases above the Curie temperature
      T(c). The ratio gamma/J(M) monotonically decreases with increasing temperature
      without an anomaly at T(c).

PMID- 23004324
TI  - Two-dimensional Heisenberg behavior of J(eff)=1/2 isospins in the paramagnetic
      state of the spin-orbital Mott insulator Sr2IrO4.
AB  - The dynamical correlations of J(eff)=1/2 isospins in the paramagnetic state of
      spin-orbital Mott insulator Sr2IrO4 were revealed by resonant magnetic x-ray
      diffuse scattering. We found a two-dimensional antiferromagnetic fluctuation with
      a large in-plane correlation length exceeding 100 lattice spacings at even 20 K
      above the magnetic ordering temperature. In marked contrast to the naive
      expectation of the strong magnetic anisotropy associated with an enhanced spin
      orbit coupling, we discovered an isotropic isospin correlation that is well
      described by the two-dimensional S=1/2 quantum Heisenberg model. The estimated
      antiferromagnetic coupling constant as large as J~0.1  eV that is comparable to
      the small Mott gap (<0.5  eV) points out the weak and marginal Mott character of
      this spin-orbital entangled system.

PMID- 23004325
TI  - Gd-based single-ion magnets with tunable magnetic anisotropy: molecular design of
      spin qubits.
AB  - We report ac susceptibility and continuous wave and pulsed EPR experiments
      performed on GdW10 and GdW30 polyoxometalate clusters, in which a Gd3+ ion is
      coordinated to different polyoxometalate moieties. Despite the isotropic
      character of gadolinium as a free ion, these molecules show slow magnetic
      relaxation at very low temperatures, characteristic of single molecule magnets.
      For T?200  mK, the spin-lattice relaxation becomes dominated by pure quantum
      tunneling events, with rates that agree quantitatively with those predicted by
      the Prokof'ev and Stamp model [Phys. Rev. Lett. 80, 5794 (1998)]. The sign of the
      magnetic anisotropy, the energy level splittings, and the tunneling rates
      strongly depend on the molecular structure. We argue that GdW30 molecules are
      also promising spin qubits with a coherence figure of merit Q(M)?50.

PMID- 23004326
TI  - Electric dipolar Kondo effect emerging from a vibrating magnetic ion.
AB  - When a magnetic ion vibrates in a metal, it inevitably introduces a new channel
      of hybridization with conduction electrons, and in general, the vibrating ion
      induces an electric dipole moment. In such a situation, we find that magnetic and
      nonmagnetic Kondo effects alternatively occur due to the screening of the spin
      moment and electric dipole moment of the vibrating ion. In particular, the
      electric dipolar two-channel Kondo effect is found to occur for a weak Coulomb
      interaction. We also show that a magnetically robust heavy-electron state appears
      near the fixed point of the electric dipolar two-channel Kondo effect. We believe
      that the vibrating magnetic ion opens a new door in Kondo physics.

PMID- 23004327
TI  - Orbital disorder induced by charge fluctuations in vanadium spinels.
AB  - Motivated by recent experiments on vanadium spinels, AV2O4, that show an
      increasing degree of electronic delocalization for smaller cation sizes, we study
      the evolution of orbital ordering (OO) between the strong and intermediate
      coupling regimes of a multiorbital Hubbard Hamiltonian. The underlying magnetic
      ordering of the Mott insulating state leads to a rapid suppression of OO due to
      enhanced charge fluctuations along ferromagnetic bonds. Orbital double occupancy
      is rather low at the transition point indicating that the system is in the
      crossover region between strong and intermediate-coupling regimes when the
      orbital degrees of freedom become disordered.

PMID- 23004328
TI  - Resonating valence bond wave functions and classical interacting dimer models.
AB  - We relate properties of nearest-neighbor resonating valence-bond (NNRVB) wave
      functions for SU(g) spin systems on two-dimensional bipartite lattices to those
      of fully packed interacting classical dimer models on the same lattice. The
      interaction energy can be expressed as a sum of n-body potentials V(n), which are
      recursively determined from the NNRVB wave function on finite subgraphs of the
      original lattice. The magnitude of the n-body interaction V(n) (n>1) is of order
      O(g(-(n-1))) for small g(-1). The leading term is a two-body nearest-neighbor
      interaction V2(g) favoring two parallel dimers on elementary plaquettes. For
      SU(2) spins, using our calculated value of V2(g=2), we find that the long
      distance behavior of the bond-energy correlation function is dominated by an
      oscillatory term that decays as 1/|r|alpha with alpha~1.22. This result is in
      remarkable quantitative agreement with earlier direct numerical studies of the
      corresponding wave function, which give alpha~1.20.

PMID- 23004329
TI  - Resonant excitation of graphene k-phonon and intra-landau-level excitons in
      magneto-optical spectroscopy [corrected].
AB  - Precise infrared magnetotransmission experiments have been performed in magnetic
      fields up to 32 T on a series of multilayer epitaxial graphene samples. We
      observe changes in the spectral features and broadening of the main cyclotron
      transition when the incoming photon energy is in resonance with the lowest Landau
      level separation and the energy of a K point optical phonon. We have developed a
      theory that explains and quantitatively reproduces the frequency and magnetic
      field dependence of the phenomenon as the absorption of a photon together with
      the simultaneous creation of an intervalley, intra-Landau-level exciton, and a K
      phonon.

PMID- 23004330
TI  - Broken local symmetry in paraelectric BaTiO3 proved by second harmonic
      generation.
AB  - Precursor dynamics of a cubic to tetragonal ferroelectric phase transition in
      BaTiO3 is studied by the accurate measurement of the second harmonic generation
      (SHG) integral intensities. A finite signal holds for the SHG integrated
      intensity above the ferroelectric Curie temperature T(c)=403  K. Above the Burn's
      temperature T(d)~580  K, the power law with the exponent gamma=1 shows normal SHG
      nature originating from the hyper-Raman scattering by dynamical polar
      excitations, while, below T(d), a SHG signal from polar nanoregions becomes
      dominant with the larger exponent gamma=2. Such a crossover of the power law
      exponent near T(d) is discussed on the basis of the effective Hamiltonian method
      and Monte Carlo simulation.

PMID- 23004331
TI  - Orientational order of carbon nanotube guests in a nematic host suspension of
      colloidal viral rods.
AB  - In order to investigate the coupling between the degrees of alignment of
      elongated particles in binary nematic dispersions, surfactant stabilized single
      wall carbon nanotubes (CNTs) have been added to nematic suspensions of colloidal
      rodlike viruses in aqueous solution. We have independently measured the
      orientational order parameter of both components of the guest-host system by
      means of polarized Raman spectroscopy and by optical birefringence, respectively.
      Our system allows us therefore to probe the regime where the guest particles
      (CNTs) are shorter and thinner than the fd virus host particles. We show that the
      degree of order of the CNTs is systematically smaller than that of the fd virus
      particles for the whole nematic range. These measurements are in good agreement
      with predictions of an Onsager-type second-viral theory, which explicitly
      includes the flexibility of the virus particles, and the polydispersity of the
      CNTs.

PMID- 23004332
TI  - Gelation via ion exchange in discotic suspensions.
AB  - The phase behavior of charged disk suspensions displays a strong dependence on
      ionic strengths, as the interplay between excluded volume and electrostatic
      interactions determines the formation of glasses, gels, and liquid crystal
      states. The various ions in natural soil or brine, however, could present
      additional effects, especially considering that most platelet structures bear a
      momentous ion-exchange capacity. Here we observed how ion exchange modulates and
      controls the interaction between individual disks and leads to unconventional
      phase transitions from isotropic gel to nematic gel and finally to nematic liquid
      crystals.

PMID- 23004333
TI  - Spatiotemporal evolution of thin liquid films during impact of water bubbles on
      glass on a micrometer to nanometer scale.
AB  - Collisions between millimeter-size bubbles in water against a glass plate are
      studied using high-speed video. Bubble trajectory and shape are tracked
      simultaneously with laser interferometry between the glass and bubble surfaces
      that monitors spatial-temporal evolution of the trapped water film. Initial
      bubble bounces and the final attachment of the bubble to the surface have been
      quantified. While the global Reynolds number is large (~10(2)), the film Reynolds
      number remains small and permits analysis with lubrication theory with
      tangentially immobile boundary condition at the air-water interface. Accurate
      predictions of dimple formation and subsequent film drainage are obtained.

PMID- 23004334
TI  - Flow rate of particles through apertures obtained from self-similar density and
      velocity profiles.
AB  - "Beverloo's law" is considered as the standard expression to estimate the flow
      rate of particles through apertures. This relation was obtained by simple
      dimensional analysis and includes empirical parameters whose physical meaning is
      poorly justified. In this Letter, we study the density and velocity profiles in
      the flow of particles through an aperture. We find that, for the whole range of
      apertures studied, both profiles are self-similar. Hence, by means of the
      functionality obtained for them the mass flow rate is calculated. The comparison
      of this expression with the Beverloo's one reveals some differences which are
      crucial to understanding the mechanism that governs the flow of particles through
      orifices.

PMID- 23004335
TI  - Shaken granular lasers.
AB  - Granular materials have been studied for decades, driven by industrial and
      technological applications. These very simple systems, composed of agglomerations
      of mesoscopic particles, are characterized, in specific regimes, by a large
      number of metastable states and an extreme sensitivity (e.g., in sound
      transmission) to the arrangement of grains; they are not substantially affected
      by thermal phenomena, but can be controlled by mechanical solicitations. Laser
      emission from shaken granular matter is so far unexplored. Here we provide
      experimental evidence that laser emission can be affected and controlled by the
      status of the motion of the granular material; we also find that competitive
      random lasers can be observed. We hence demonstrate the potentialities of gravity
      affected moving disordered materials for optical applications, and open the road
      to a variety of novel interdisciplinary investigations, involving modern
      statistical mechanics and disordered photonics.

PMID- 23004336
TI  - Pattern formation in self-propelled particles with density-dependent motility.
AB  - We study the behavior of interacting self-propelled particles, whose self
      propulsion speed decreases with their local density. By combining direct
      simulations of the microscopic model with an analysis of the hydrodynamic
      equations obtained by explicitly coarse graining the model, we show that
      interactions lead generically to the formation of a host of patterns, including
      moving clumps, active lanes, and asters. This general mechanism could explain
      many of the patterns seen in recent experiments and simulations.

PMID- 23004337
TI  - Growth laws and self-similar growth regimes of coarsening two-dimensional foams:
      transition from dry to wet limits.
AB  - We study the topology and geometry of two-dimensional coarsening foam with an
      arbitrary liquid fraction. To interpolate between the dry limit described by von
      Neumann's law and the wet limit described by Marqusee's equation, the relevant
      bubble characteristics are the Plateau border radius and a new variable: the
      effective number of sides. We propose an equation for the individual bubble
      growth rate as the weighted sum of the growth through bubble-bubble interfaces
      and through bubble-Plateau border interfaces. The resulting prediction is
      successfully tested, without an adjustable parameter, using extensive
      bidimensional Potts model simulations. The simulations also show that a self
      similar growth regime is observed at any liquid fraction, and they also determine
      how the average size growth exponent, side number distribution, and relative size
      distribution interpolate between the extreme limits. Applications include
      concentrated emulsions, grains in polycrystals, and other domains with coarsening
      that is driven by curvature.

PMID- 23004338
TI  - Comment on "Ordering of small particles in one-dimensional coherent structures by
      time-periodic flows".

PMID- 23004340
TI  - P2Y purinoceptors as potential emerging therapeutical target in vascular disease.
AB  - In the last two decades a tremendous development has been noticed in our
      understanding of the purinergic system, consisting of heterogeneously expressed
      purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate,
      uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert
      multiple effects on the vascular system: they regulate the relaxation and
      constriction of arterial blood vessels, lead to proliferation and migration in
      endothelial cells and vascular smooth muscle cells, and mediate potent
      proinflammatory responses or phenotypic cell changes. This review focuses on the
      P2 purinoceptor subtype P2Y and its pleiotropic effects in the vascular wall
      under physiological and pathophysiological condition. Various experimental and
      clinical studies provide evidence that pharmacological targeting of P2Y might be
      effective in reducing vascular alterations under disease conditions.

PMID- 23004341
TI  - Genotyping SSR length variants by isothermal DNA amplification.
AB  - Loop-mediated isothermal DNA amplification (LAMP) is an alternative method for
      the amplification of DNA sequences. It has been applied primarily for the
      detection of specific targets. We demonstrate the novel use of LAMP to amplify
      SSR alleles in a set of rice varieties and show the results to be consistent with
      analysis performed by PCR. Furthermore, we test the sensitivity of the assay and
      show it to amplify from near single copy target.

PMID- 23004342
TI  - The relationship between oxidative stress, smoking and the clinical severity of
      psoriasis.
AB  - BACKGROUND: Recent studies suggested that increased oxidant products and
      decreased antioxidant system functions may be involved in the pathogenesis of
      psoriasis. In this study, we investigated total oxidative status, Paraoxonase
      (PON)1/arylesterase enzyme activities and severity of the disease in smoker and
      non-smoker psoriatic patients. METHODS: Fifty-four patients with plaque type
      psoriasis (28 smokers and 26 non-smokers) and 62 healthy volunteers (16 smokers
      and 46 non-smokers) were enrolled in the study. Serum total oxidant status (TOS),
      total antioxidant capacity (TAC) and arylesterase levels were measured, and
      oxidative stress index (OSI) was calculated in all participants. RESULTS:
      Psoriasis Area and Severity Index scores were significantly higher in smoker
      patients than in non-smoker patients (P = 0.014). Both smoker and non-smoker
      patients had significantly increased TOS levels and OSI values and decreased TAC
      levels than healthy subjects (all P values = 0.000). The TAC and TOS levels, OSI
      values and arylesterase activities were similar between smoker and non-smoker
      patients. The levels of triglyceride (TG), total cholesterol (TC), low-density
      lipoprotein (LDL) and high-density lipoprotein (HDL) were not significantly
      different between smoker and non-smoker psoriasis patients. When compared with
      non-smoking controls, only smoking psoriasis patients had significantly higher TG
      (P = 0.005), lower HDL (P = 0.022) and lower arylesterase levels (P = 0.015).
      There were no significant correlations with Psoriasis Area and Severity Index
      (PASI) scores and TAC, TOS, OSI, TG, TC, HDL and LDL levels in all psoriasis
      patients. CONCLUSIONS: Oxidative stress is increased in psoriasis patients
      regardless of their smoking status. The decreased arylesterase activity in smoker
      psoriasis patients suggested that smoking may be a considerable risk factor that
      increases the severity of psoriasis by increasing oxidative stress in these
      patients.

PMID- 23004343
TI  - Blood pressure and blood volume: acute and chronic considerations in
      hemodialysis.
AB  - Hypertension is highly prevalent yet poorly controlled in the majority of
      dialysis patients and represents a significant burden of disease, with rates of
      morbidity and mortality greater than those in the general population. In
      dialysis, blood volume plays a critical role in the pathogenesis of hypertension,
      with expansion of extracellular volume increasingly recognized as an independent
      risk factor for morbidity and mortality. Within the current paradigm of dialysis
      prescription the majority of patients remain chronically volume expanded.
      However, management of blood pressure and volume state is difficult for
      clinicians with a paucity of randomized evidence adding to the complexity of
      nonlinear morbidity and mortality associations. With dialysis itself as a
      significant cardiac stressor, control of volume state is critical to minimize
      intradialytic hemodynamic instability, aid in preservation of cardiac anatomy and
      prevent progression to cardiovascular morbidity and mortality. This review
      explores the relationship of blood volume to blood pressure and potential targets
      for management in this at risk population.

PMID- 23004344
TI  - Central blood pressure is an independent predictor of future hypertension in
      young to middle-aged stage 1 hypertensives.
AB  - AIM: The aim of the present study was to evaluate the association of central
      blood pressure (BP) with organ damage and risk of future hypertension in a cohort
      of young to middle-aged patients. METHODS: We studied 305 subjects screened for
      stage 1 hypertension to determine which subjects developed hypertension needing
      therapy according to current guidelines. Central BP was obtained from radial
      artery tonometry. Organ damage was the presence of left ventricular hypertrophy
      and/or microalbuminuria. RESULTS: In a multiple logistic regression including
      ambulatory 24-h BP, central mean BP was associated with presence of end-organ
      damage (p = 0.003). In the subjects divided according to whether their central
      mean BP was above or below the median, subjects with high central mean BP
      presented an earlier impairment of arterial distensibility and developed
      sustained hypertension more frequently compared with those with low central mean
      BP (p < 0.001). In logistic analyses, central mean BP was an independent
      predictor of future hypertension (p < 0.001) and remained associated with outcome
      when 24-h BP was included in the same model (p = 0.006). CONCLUSIONS: In young to
      middle-aged subjects in the early stage of hypertension, central mean BP is a
      useful adjunct to brachial BPs to better define the individual risk profile.

PMID- 23004345
TI  - Design and development of a field applicable gold nanosensor for the detection of
      luteinizing hormone.
AB  - In this paper, we describe a novel strategy for the fabrication of a nanosensor
      for detecting luteinizing hormone (LH) of sheep using a gold nanoparticle-peptide
      conjugate. A new peptide sequence "CDHPPLPDILFL" (leutinizing hormone peptide,
      LHP) has been identified, using BLAST and Clustal W analysis, to detect antibody
      of LH (sheep). LHP has been synthesized and characterized, and their affinity
      toward anti-LH was established using enzyme linked immunosorbant assay (ELISA)
      technique. The thiol group in LHP directly binds with gold nanoparticles (AuNPs)
      to yield AuNP-LHP construct. Detailed physicochemical analysis of AuNP-LHP
      construct was determined using various analytical techniques. Nanosensor using
      gold nanoparticle peptide conjugate was developed on the basis of competitive
      binding of AuNP-LHP and LH toward anti-LH. Nitrocellulose membrane, precoated
      with anti-LH, was soaked in the mixture of AuNP-LHP and sample of analysis (LH).
      In the absence of LH (sheep), anti-LH coated on the membrane binds with AuNP-LHP,
      leading to a distinctive red color, while in the presence of LH, no color
      appeared in the membrane due to the interaction of anti-LH with LH thereby
      preventing the binding of AuNP-LHP with membrane bound anti-LH. The sensor assay
      developed in this study can detect LH (sheep) up to a minimal concentration of
      ~50 ppm with a high degree of reproducibility and selectivity. The gold
      nanoparticle-peptide based nanosensor would be a simple, portable, effective, and
      low cost technique for infield applications.

PMID- 23004346
TI  - Cyclam-based polymeric copper chelators for gene delivery and potential PET
      imaging.
AB  - A series of reducible polycationic copper chelators (RPCs) based on 1,4,8,11
      tetraazacyclotetradecane (cyclam) were synthesized by Michael addition. Molecular
      weight of the polycations was controlled by reaction stoichiometry and reaction
      conditions, resulting in polymers with molecular weights ranging from 4400 to 13
      800. The cyclam moieties in the polycations retained their ability to form
      complexes with Cu(II). The presence of disulfide bonds in the polycations
      resulted in substantially lower cytotoxicity than control 25 kDa
      poly(ethyleneimine). RPC as well as their complexes with Cu(II) exhibited high
      transfection activity in vitro. The reported polycationic Cu(II) chelates
      represent promising nucleic acid delivery vectors with potential for future
      theranostic applications.

PMID- 23004347
TI  - Long-term results of concurrent chemoradiotherapy using cisplatin and vinorelbine
      for stage III non-small-cell lung cancer.
AB  - Concurrent chemoradiotherapy is the standard treatment for unresectable stage III
      non-small cell lung cancer (NSCLC). The long-term feasibility and efficacy of
      vinorelbine and cisplatin with concurrent thoracic radiotherapy were
      investigated. Eighteen patients received cisplatin (80 mg/m(2)) on day 1 and
      vinorelbine (20 mg/m(2) in level 1, and 25 mg/m(2) in level 2) on days 1 and 8
      every 4 weeks for four cycles in a phase I trial. Ninety-three patients received
      the same chemotherapy regimen except for the fixed vinorelbine (20 mg/m(2))
      dosage and consolidation therapy with docetaxel (60 mg/m(2), every 3 weeks). The
      thoracic radiotherapy consisted of a single dose of 2 Gy once daily to a total
      dose of 60 Gy. A total of 111 patients were analyzed in the present study:
      male/female, 91/20; median age, 60 years; stage IIIA/IIIB, 50/61; and
      squamous/non-squamous histology, 26/85. The 3-, 5-, and 7-year overall survival
      rates (95% CI) were 43.2% (33.9-52.2), 25.2% (17.6-33.5), and 23.2% (15.8-31.4),
      respectively. The median progression-free survival and median survival time (95%
      CI) were 13.5 (10.1-16.7) months and 30.0 (24.3-38.8) months, respectively. Four
      patients (4%) experienced Grade 5 pulmonary toxicities from 4.4 to 9.4 months
      after the start of treatment. In conclusion, approximately 15% of patients with
      unresectable stage III NSCLC could be cured with chemoradiotherapy without severe
      late toxicities after 10 months of follow-up. Although based on the data from
      highly selected population participated in phase I and phase II trial, this
      analysis would strengthen and confirm the previous reports concerning concurrent
      chemoradiotherapy with third generation cytotoxic agents.

PMID- 23004348
TI  - An experimental study of the gas-phase reactions of NO3 radicals with a series of
      unsaturated aldehydes: trans-2-hexenal, trans-2-heptenal, and trans-2-octenal.
AB  - Rate constants for the gas-phase reactions of the NO(3) radical with a series of
      unsaturated aldehydes, trans-2-hexenal, trans-2-heptenal, and trans-2-octenal,
      have been measured using absolute rate method at 294 +/- 3 K and atmospheric
      pressure. This work was performed to clarify discrepancies found in the
      literature and thus led to a clearer view of the effect of the increasing carbon
      chain length on the reactivity of trans-2-alkenals. The rate constants were
      determined to be (4.7 +/- 1.5) * 10(-15), (5.3 +/- 1.6) * 10(-15), and (5.6 +/-
      2.3) * 10(-15) cm(3) molecule(-1) s(-1) for trans-2-hexenal, trans-2-heptenal,
      and trans-2-octenal, respectively. These results clearly indicate that the carbon
      chain lengthening of the trans-2-alkenals does not significantly affect the rate
      constant. In addition, the mechanism for the reaction of NO(3) with these
      unsaturated aldehydes was also investigated. Unsaturated peroxynitrate-type
      compounds that are exclusively formed through the abstraction channel were
      observed as the main products.

PMID- 23004349
TI  - Circadian typology: a comprehensive review.
AB  - The interest in the systematic study of the circadian typology (CT) is relatively
      recent and has developed rapidly in the two last decades. All the existing data
      suggest that this individual difference affects our biological and psychological
      functioning, not only in health, but also in disease. In the present study, we
      review the current literature concerning the psychometric properties and validity
      of CT measures as well as individual, environmental and genetic factors that
      influence the CT. We present a brief overview of the biological markers that are
      used to define differences between CT groups (sleep-wake cycle, body temperature,
      cortisol and melatonin), and we assess the implications for CT and adjustment to
      shiftwork and jet lag. We also review the differences between CT in terms of
      cognitive abilities, personality traits and the incidence of psychiatric
      disorders. When necessary, we have emphasized the methodological limitations that
      exist today and suggested some future avenues of work in order to overcome these.
      This is a new field of interest to professionals in many different areas
      (research, labor, academic and clinical), and this review provides a state of the
      art discussion to allow professionals to integrate chronobiological aspects of
      human behavior into their daily practice.

PMID- 23004350
TI  - Stable Cu(I) complexes with thioamidoguanidine possessing halide-bridge
      structure.
AB  - Treatment of an aryl-sec-alkyl unsymmetrical thiourea (Tu) with Cu(II)X(2) (X =
      I, Br) transform the thiourea (Tu) into a thioamidoguanidino (Tag) moiety with
      concomitant reduction of Cu(II) to Cu(I), which forms a [Cu(2)(I)(MU(2)
      X)(2)Tag(2)] (X = I (for A) and X = Br (for B)) complex. Meanwhile, the treatment
      of same unsymmetrical thiourea (Tu) with Cu(I)X (X = Br) forms a stable cluster
      with a [Cu(I)(3)(MU(2)-S)(4)Tu(4)X(3)] core (C). Single crystal X-ray diffraction
      revealed that compounds A and B exhibit 1D chain with a Cu(2)(MU(2)-X)(2) core,
      whereas compound C is a Cu(I)(3)S(4)Br(3) cluster. Compound A is centrosymmetric
      due to the trans orientation of two Tag units whereas compound B is ascentric due
      to the cis orientation of two Tag units. In compound A, the Cu(2)I(2) core is
      perfectly rhomboidal where the iodine atoms are trans oriented. However in
      compound B, the Cu(2)Br(2) core is not perfectly rhomboidal (bowl shaped) and the
      bromine atoms are cis oriented. It is interesting to note that although the Tag
      moiety in compounds A and B contain two morpholine-O atoms; only one of the
      morpholine-O atoms (O2) is involved in the generation of three-dimensional
      network. The Cu(I)(3)S(4)Br(3) cluster in compound C contains one tri- and two
      tetra-coordinated Cu(I) centers. The Cu(I) cluster in C contains a Cu(2)(MU(2)
      S)(2) rhomboidal plane exhibiting a chair and a boat form containing the
      Cu(I)(3)S(3) unit. In compounds A and B, the two Cu(I) centers are MU(2)-X
      bridged and have a MU(1)-S linkage, whereas in compound C the linkages are
      opposite having four MU(2)-S bridges and three MU(1)-Br linkages.

PMID- 23004352
TI  - Incidence and survival patterns of cutaneous T-cell lymphomas in the United
      States.
AB  - Using the United States Surveillance, Epidemiology and End Results (SEER) 17
      dataset, we examined incidence and survival patterns for patients with cutaneous
      T-cell lymphomas (CTCLs) diagnosed following institution of the World Health
      Organization-European Organisation for Research and Treatment of Cancer (WHO
      EORTC) classification. From 2005 to 2008, 2273 cases of CTCL were diagnosed. The
      age-adjusted incidence rate per 100,000 person-years for mycosis fungoides (MF)
      was 0.55 and for Sezary syndrome (SS) was 0.01. Incidence was higher among males
      (MF/SS male-to-female incidence rate ratio [IRR] 1.57) and black patients (MF
      black-to-white IRR 1.55). Black patients with CTCL were diagnosed at a younger
      age and black patients with MF/SS presented with advanced stage and had worse
      survival than white patients. In multiple-variable Cox-regression models, age >
      60 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.97-7.70), black race
      (HR 2.09, 95% CI 1.29-3.37) and advanced stage (HR 6.06, 95% CI 3.66-10.05)
      predicted worse survival for patients with MF/SS. Additional research identifying
      reasons for these differences are necessary to better understand these diseases
      and for new strategies in the treatment of CTCL.

PMID- 23004351
TI  - Evidence-based control of canine rabies: a critical review of population density
      reduction.
AB  - Control measures for canine rabies include vaccination and reducing population
      density through culling or sterilization. Despite the evidence that culling fails
      to control canine rabies, efforts to reduce canine population density continue in
      many parts of the world. The rationale for reducing population density is that
      rabies transmission is density-dependent, with disease incidence increasing
      directly with host density. This may be based, in part, on an incomplete
      interpretation of historical field data for wildlife, with important implications
      for disease control in dog populations. Here, we examine historical and more
      recent field data, in the context of host ecology and epidemic theory, to
      understand better the role of density in rabies transmission and the reasons why
      culling fails to control rabies. We conclude that the relationship between host
      density, disease incidence and other factors is complex and may differ between
      species. This highlights the difficulties of interpreting field data and the
      constraints of extrapolations between species, particularly in terms of control
      policies. We also propose that the complex interactions between dogs and people
      may render culling of free-roaming dogs ineffective irrespective of the
      relationship between host density and disease incidence. We conclude that
      vaccination is the most effective means to control rabies in all species.

PMID- 23004353
TI  - Enhancement of viniferin production in Vitis vinifera L. cv. Alphonse Lavallee
      Cell suspensions by low-energy ultrasound alone and in combination with methyl
      jasmonate.
AB  - This study examined for the first time the effect of low-energy ultrasound (US),
      used alone or in combination with methyl jasmonate (MeJA), on viniferin
      production in cell cultures of Vitis vinifera L. cv Alphonse Lavallee. Cell
      suspensions were exposed for 2 min to US (power 30, 60, and 90 mW cm(-3)). The
      highest viniferin production was obtained at 30 mW cm(-3). When sonication was
      performed twice, the effect on viniferin production was negligible, whereas
      triple sonication slightly increased production. US treatment at 30 mW cm(-3) for
      5 min decreased viniferin production and induced cellular death. The combined use
      of MeJA and US (2 min) increased the production of delta-viniferin, the dominant
      stilbene, more than each elicitor used alone. These results suggest that low
      energy US, alone and in combination with MeJA, can act as a physical elicitor to
      stimulate viniferin production in V. vinifera cell cultures.

PMID- 23004354
TI  - Microwave and continuous flow technologies in drug discovery.
AB  - INTRODUCTION: Microwave and continuous flow microreactors have become mainstream
      heating sources in contemporary pharmaceutical company laboratories. Such
      technologies will continue to benefit from design and engineering improvements,
      and now play a key role in the drug discovery process. AREAS COVERED: The authors
      review the applications of flow- and microwave-mediated heating in library,
      combinatorial, solid-phase, metal-assisted, and protein chemistries.
      Additionally, the authors provide a description of the combination of microwave
      and continuous flow platforms, with applications in the preparation of
      radiopharmaceuticals and in drug candidate development. Literature reviewed is
      chiefly 2000 - 2012, plus key citations from earlier reports. EXPERT OPINION:
      With the advent of microwave irradiation, reactions that normally took days to
      complete can now be performed in a matter of minutes. Coupled with the
      introduction of continuous flow microreactors, pharmaceutical companies have an
      easy way to improve the greenness and efficiency of many synthetic operations.
      The combined force of these technologies offers the potential to revolutionize
      discovery and manufacturing processes.

PMID- 23004356
TI  - Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting
      the function of dendritic cells through the nuclear farnesoid X receptor.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid
      with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic
      degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is
      unknown whether UDCA would also modulate eosinophilic inflammation outside the
      gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in
      asthma. The working mechanism for its immunomodulatory effect is unknown.
      METHODS: The immunosuppressive features of UDCA were studied in vivo, in mice, in
      an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the
      mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T
      cells, and dendritic cell (DCs). DC function was studied in greater detail,
      focussing on migration and T-cell stimulatory strength in vivo and interaction
      with T cells in vitro as measured by time-lapse image analysis. Finally, we
      studied the capacity of UDCA to influence DC/T cell interaction. RESULTS:
      Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol
      challenge significantly reduced eosinophilic airway inflammation compared with
      control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic
      acid strongly promoted interleukin (IL)-12 production and enhanced the migration
      in DCs. The time of interaction between DCs and T cells was sharply reduced in
      vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine
      production. Ursodeoxycholic acid-treated DCs have less capacity than saline
      treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice.
      CONCLUSION: Ursodeoxycholic acid has the potency to suppress eosinophilic
      inflammation outside the GI tract. This potential comprises to alter critical
      function of DCs, in essence, the effect of UDCA on DCs through the modulation of
      the DC/T cell interaction.

PMID- 23004355
TI  - Silibinin inhibits VEGF secretion and age-related macular degeneration in a
      hypoxia-dependent manner through the PI-3 kinase/Akt/mTOR pathway.
AB  - BACKGROUND AND PURPOSE: Hypoxia-mediated neovascularization plays an important
      role in age-related macular degeneration (AMD). There are few animal models or
      effective treatments for AMD. Here, we investigated the effects of the flavonoid
      silibinin on hypoxia-induced angiogenesis in a rat AMD model. EXPERIMENTAL
      APPROACH: Retinal pigmented epithelial (RPE) cells were subjected to hypoxia in
      vitro and the effects of silibinin on activation of key hypoxia-induced pathways
      were examined by elucidating the hypoxia-inducible factor-1 alpha (HIF-1alpha)
      protein level by Western blot. A rat model of AMD was developed by intravitreal
      injection of VEGF in Brown Norway rats, with or without concomitant exposure of
      animals to hypoxia. Animals were treated with oral silibinin starting at day 7
      post-VEGF injection and AMD changes were followed by fluorescein angiography on
      days 14 and 28 post-injection. KEY RESULTS: Silibinin pretreatment of RPE cells
      increased proline hydroxylase-2 expression, inhibited HIF-1alpha subunit
      accumulation, and inhibited VEGF secretion. Silibinin-induced HIF-1alpha and VEGF
      down-regulation required suppression of hypoxia-induced phosphatidylinositol 3
      kinase/Akt/mammalian target of rapamycin (mTOR) pathway. In the rat model of AMD,
      silibinin administration prevented VEGF- and VEGF plus hypoxia-induced retinal
      oedema and neovascularization. CONCLUSION AND IMPLICATIONS: The effects of
      silibinin, both in vitro and in vivo, support its potential as a therapeutic for
      the prevention of neovascular AMD.

PMID- 23004357
TI  - Use of systemic corticosteroids in management of a large congenital haemangioma
      of the scalp.
AB  - Congenital haemangiomas are rare and are estimated to have a combined incidence
      of less than 3% of all infantile haemangiomas. They are fully grown at birth,
      having undergone their proliferative phase in utero. Congenital hemangiomas can
      present at birth or in some cases can be detected antenatally on imaging. In the
      majority of patients no therapeutic intervention is required. Congenital
      hemangiomas also differ from infantile hemangiomas by staining negatively with
      GLUT1 antibody. They fall into two major subtypes: rapidly involuting congenital
      hemangiomas (RICHs) and noninvoluting congenital hemangiomas (NICHs). Here we
      describe a case of RICH detected antenatally on ultrasound imaging. This lesion
      caused significant complications in the postnatal period due to the bulk of the
      lesion and the presence of incipient ulceration with the risk of possible
      catastrophic hemorrhage. A therapeutic trial of oral corticosteroid was commenced
      in an effort to accelerate involution due to the significant risk associated with
      other possible treatment modalities such as embolization or surgical
      intervention.

PMID- 23004358
TI  - The ammonium/nitrate ratio is an input signal in the temperature-modulated, SNC1
      mediated and EDS1-dependent autoimmunity of nudt6-2 nudt7.
AB  - AtNUDT7 was reported to be a negative regulator of EDS1-mediated immunity in
      Arabidopsis. However, the underlying molecular and genetic mechanism of the
      AtNUDT7-regulated defense pathway remains elusive. Here we report that AtNUDT7
      and its closest paralog AtNUDT6 function as novel negative regulators of SNC1, a
      TIR-NB-LRR-type R gene. SNC1 is upregulated at transcriptional and possibly post
      transcriptional levels in nudt6-2 nudt7. The nudt6-2 nudt7 double mutant exhibits
      autoimmune phenotypes that are modulated by temperature and fully dependent on
      EDS1. The nudt6-2 nudt7 mutation causes EDS1 nuclear accumulation shortly after
      the establishment of autoimmunity caused by the temperature shift. We found that
      a low ammonium/nitrate ratio in growth media leads to a higher level of nitrite
      dependent nitric oxide (NO) production in nudt6-2 nudt7, and NO acts in a
      positive feedback loop with EDS1 to promote the autoimmunity. The low
      ammonium/nitrate ratio also enhances autoimmunity in snc1-1 and cpr1, two other
      autoimmune mutants in Arabidopsis. Our study indicates that Arabidopsis senses
      the ammonium/nitrate ratio as an input signal to determine the amplitude of the
      EDS1-mediated defense response, probably through the modulation of NO production.

PMID- 23004359
TI  - Structure and dynamics of cardiotoxins.
AB  - Cytotoxins (or cardiotoxins; CTs) are toxins from cobra venom characterized by
      the three-finger (TF) fold. CTs are on average 60-residue-long peptides,
      possessing as many as 4 disulfide bonds. The elements of antiparallel beta
      structure take origin from the hydrophobic core formed by the disulfides. The
      beta-strands adopt the shape of the three loops, giving the name of the fold.
      While neurotoxins (NTs) - also TF proteins from snake venom - exert their effect
      through specific interactions with protein receptors, no specific protein target
      has been found for CTs. Unlike NTs, CTs are amphiphilic and cytotoxic against a
      variety of cells, including cancer ones. Thus, the hypothesis that the activity
      of CTs is caused by their interactions with lipid membranes is currently central.
      To understand molecular basis behind variations in toxicities of CTs highly
      homologous in their sequences, detailed knowledge of their structure and dynamics
      is required. The present review summarizes experimental and computational data on
      the spatial organization of CTs and their dynamics in various environments
      (aqueous solution, membranous milieus).

PMID- 23004360
TI  - Solution NMR study of the transmembrane domain of single-span membrane proteins:
      opportunities and strategies.
AB  - Membrane proteins play important roles in signal transduction across the cell
      membrane. Structural information for the membrane proteins is still limited due
      to many technical challenges. Membrane proteins containing a single alpha-
      helical transmembrane (TM) domain are very important in several pathways.
      Solution NMR spectroscopy is an important tool for the study of the structure of
      the TM domain of these types of proteins due to their small size. In this review,
      we summarize the importance of some single-span membrane proteins in signal
      transduction and the importance of understanding the structure of the TM domain.
      We discussed the current progress in the structural study of these types of
      proteins using solution NMR spectroscopy. We summarize the structures solved
      during last several years. The structures of the regulatory domain of the ion
      channels such as KCNE1, integrin and viral proteins such as the M2 channel are
      described. The binding interface of single TM-TM domains is discussed based on
      NMR structural studies. Strategies including sample preparation, detergent
      screening, and structural determination of single-span membrane protein are
      summarized. We also discuss the potential application of NMR spectroscopy to drug
      discovery of proteins with a single-span TM domain.

PMID- 23004361
TI  - Clinical experience with intraoperative jugular venous oximetry during pediatric
      intracranial neurosurgery.
AB  - AIM: To report our institutional experience with intraoperative jugular venous
      oximetry during pediatric intracranial surgery to guide anesthetic care.
      BACKGROUND: The utility of intraoperative jugular venous oximetry in adults
      undergoing intracranial surgery is well known. However, there is a little
      information on its' application in children during intracranial surgery. METHODS:
      After IRB approval, we examined patient, equipment, placement, and sampling
      characteristics for jugular bulb catheters in children aged <18 years who were
      monitored with jugular oximetry during elective intracranial surgery between 2006
      and 2010. We also determined the prevalence of intraoperative cerebral
      desaturation (SjvO(2) < 55%), its causes, and the interventions based on jugular
      oximetry values. RESULTS: Data from 19 children (10 males and nine females), aged
      12 +/- 1 years (range 7-17) who underwent craniotomy for arteriovenous
      malformation (AVM) resection (68%), tumor removal (21%), or aneurysm clipping
      (11%), were reviewed. We analyzed 88 coincident SjvO(2), PaCO(2), and mean
      arterial pressure data points. Eleven (58%) patients experienced at least one
      episode of cerebral desaturation. There were 25 (28%) episodes of cerebral
      desaturation, six of which we attributed to relative hypotension, four to
      hypocarbia, and 15 to a combination of both. There were no intraoperative or
      immediate postoperative (first 24 h) complications because of jugular oximetry.
      CONCLUSION: Findings from this series indicate that (i) intraoperative jugular
      venous oximetry in children is feasible in experienced hands, (ii) cerebral
      desaturation detected by jugular oximetry is common during pediatric intracranial
      procedures, and (iii) monitoring jugular venous saturation can impact anesthetic
      interventions to optimize cerebral physiology.

PMID- 23004362
TI  - Influence of a proximal margin elevation technique on marginal adaptation of
      ceramic inlays.
AB  - PURPOSE: Evaluating the effect of a proximal margin elevation technique on
      marginal adaptation of ceramic inlays. METHODS: Class II MOD-cavities were
      prepared in 40 human molars and randomly distributed to four groups (n = 10). In
      group EN (positive control) proximal margins were located in enamel, 1 mm above
      the cementoenamel junction, while 2 mm below in groups DE-1In, DE-2In and DE. The
      groups DE-1In, DE-2In and DE simulated subgingival location of the cervical
      margin. In group DE-1In one 3 mm and in group DE-2In two 1.5 mm composite layers
      (Tetric) were placed for margin elevation of the proximal cavities using Syntac
      classic as an adhesive. The proximal cavities of group DE remained untreated and
      served as a negative control. In all groups, ceramic inlays (Cerec 3D) were
      adhesively inserted. Replicas were taken before and after thermomechanical
      loading (1.200.000 cycles, 50/5 degrees C, max. load 49 N). Marginal integrity
      (tooth-composite, composite-inlay) was evaluated with scanning electron
      microscopy (200*). Percentage of continuous margin (% of total proximal margin
      length) was compared between groups before and after cycling using ANOVA and
      Scheffe post-hoc test. RESULTS: After thermomechanical loading, no significant
      differences were observed between the different groups with respect to the
      interface composite-inlay and tooth-composite with margins in dentin. The
      interface tooth-composite in enamel of group EN was significantly better compared
      to group DE-2In, which was not different to the negative control group DE and DE
      1In. CONCLUSION: Margin elevation technique by placement of a composite filling
      in the proximal box before insertion of a ceramic inlay results in marginal
      integrities not different from margins of ceramic inlays placed in dentin.

PMID- 23004562
TI  - Explicit spectral response of the geometrical isomers of a bio-active pyrazoline
      derivative encapsulated in beta-cyclodextrin nanocavity: a photophysical and
      quantum chemical analysis.
AB  - The existence of two geometrical isomers (cis- and trans-) of a biologically
      significant pyrazoline derivative [5-(-1'-(4-bromo-phenyl)-3a',7a'-hexahydro-1'H
      indazol-3'-yl)-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile] (PZ) has been
      established using a combined theoretical and experimental investigation.
      Solvatochromic analysis of PZ revealed the existence of said cis- and trans-
      isomers. The unique solvatochromic response of the PZ isomers and their
      preferential encapsulation within beta-cyclodextrin (beta-CD) nanocavity clearly
      shows the difference in the behavioral nature of the isomers of PZ in homogeneous
      and heterogeneous medium. Solvent polarity, time-resolved study, and anisotropy
      results also reinforce in favor of the existence of the isomers. To evaluate the
      actual orientation of cis and trans-PZ, the ground and excited state geometry of
      these isomers were optimized by the DFT/LanL2DZ and CIS/LanL2DZ methods,
      respectively. The experimentally observed results and the theoretically
      calculated results are found to be in close agreement.

PMID- 23004563
TI  - Quantitative structural characterization of local N-glycan microheterogeneity in
      therapeutic antibodies by energy-resolved oxonium ion monitoring.
AB  - Site-specific characterization of glycoform heterogeneity currently requires
      glycan structure assignment and glycopeptide quantification in two independent
      experiments. We present here a new method combining multiple reaction monitoring
      mass spectrometry with energy-resolved structural analysis, which we termed
      "energy-resolved oxonium ion monitoring". We demonstrated that monitoring the
      yields of oligosaccharide-derived fragment ions (oxonium ions) over a wide range
      of collision induced dissociation (CID) energy applied to a glycopeptide
      precursor exhibits a glycan structure-unique fragmentation pattern. In the
      analysis of purified immunoglobulin glycopeptides, the energy-resolved oxonium
      ion profile was shown to clearly distinguish between isomeric glycopeptides.
      Moreover, limit of detection (LOD) of glycopeptide detection was 30 attomole
      injection, and quantitative dynamic range spanned 4 orders magnitude. Therefore,
      both quantification of glycopeptides and assignment of their glycan structures
      were achieved by a simple analysis procedure. We assessed the utility of this
      method for characterizing site-specific N-glycan microheterogeneity on
      therapeutic antibodies, including validation of lot-to-lot glycoform variability.
      A significant change in the degree of terminal galactosylation was observed in
      different production lots of trastuzumab and bevacizumab. Cetuximab Fab
      glycosylation, previously known to cause anaphylaxis, was also analyzed, and
      several causative antigens including Lewis X motifs were quantitatively detected.
      The data suggests that energy-resolved oxonium ion monitoring could fulfill the
      regulatory requirement on the routine quality control analysis of forthcoming
      biosimilar therapeutics.

PMID- 23004564
TI  - Cyclization cascades initiated by 1,6-conjugate addition.
AB  - Dienyl diketones containing tethered acetates selectively undergo two different
      1,6-conjugate addition-initiated cyclization cascades. One is a 1,6-conjugate
      addition/cyclization sequence with incorporation of the nucleophile, and the
      other is catalyzed by DABCO and is thought to proceed via a cyclic acetoxonium
      intermediate. The reaction behavior of substrates lacking the tethered acetate
      was also studied. The scope of both types of cyclization cascades, the role of
      the amine additive, and the factors controlling reactivity and selectivity in the
      two different reaction pathways is discussed.

PMID- 23004565
TI  - Quality of recipient-caregiver relationship and psychological distress are
      correlates of self-care agency after lung transplantation.
AB  - Self-care behaviors are crucial for following the complex regimen after lung
      transplantation, yet little is known about recipients' levels of self-care agency
      (the capability and willingness to engage in self-care behaviors) and its
      correlates. We examined levels of self-care agency and recipient characteristics
      (socio-demographics, psychological distress, quality of relationship with primary
      lay caregiver, and health locus of control) in 111 recipients. Based on Perceived
      Self-Care Agency scores, recipients were assigned to either the low- or high-self
      care agency comparison group. Characteristics were compared between groups to
      identify characteristics likely to be associated with lower-self-care agency.
      Mean (SD) score for self-care agency (scale range, 53-265) was 223.02 (22.46).
      Recipients with lowest-self-care agency scores reported significantly poorer
      quality of caregiver relationships (p < 0.001) and greater psychological distress
      (p < 0.001). After controlling for psychological distress, the quality of the
      recipient-caregiver relationship remained significantly associated with self-care
      agency. Every one-point decrease in the quality of caregiver relationship
      increased the risk of low-self-care agency by 12%. Recipients with poorer
      caregiver relationships and greater psychological distress may need additional
      support to perform the self-care behaviors expected after lung transplantation.

PMID- 23004566
TI  - Development of NMR spectroscopic methods for dynamic detection of acetylcholine
      synthesis by choline acetyltransferase in hippocampal tissue.
AB  - Choline acetyltransferase (ChAT) is the key enzyme for acetylcholine (ACh)
      synthesis and constitutes a reliable marker for the integrity of cholinergic
      neurons. Cortical ChAT activity is decreased in the brain of patients suffering
      from Alzheimer's and Parkinson's diseases. The standard method used to measure
      the activity of ChAT enzyme relies on a very sensitive radiometric assay, but can
      only be performed on post-mortem tissue samples. Here, we demonstrate the
      possibility to monitor ACh synthesis in rat brain homogenates in real time using
      NMR spectroscopy. First, the experimental conditions of the radiometric assay
      were carefully adjusted to produce maximum ACh levels. This was important for
      translating the assay to NMR, which has a low intrinsic sensitivity. We then used
      (15) N-choline and a pulse sequence designed to filter proton polarization by
      nitrogen coupling before (1) H-NMR detection. ACh signal was resolved from
      choline signal and therefore it was possible to monitor ChAT-mediated ACh
      synthesis selectively over time. We propose that the present approach using a
      labeled precursor to monitor the enzymatic synthesis of ACh in rat brain
      homogenates through real-time NMR represents a useful tool to detect
      neurotransmitter synthesis. This method may be adapted to assess the state of the
      cholinergic system in the brain in vivo in a non-invasive manner using NMR
      spectroscopic techniques.

PMID- 23004567
TI  - Proteomic changes in the rat brain induced by homogenous irradiation and by the
      bystander effect resulting from high energy synchrotron X-ray microbeams.
AB  - PURPOSE: To further evaluate the use of microbeam irradiation (MBI) as a
      potential means of non-invasive brain tumor treatment by investigating the
      induction of a bystander effect in non-irradiated tissue. METHODS: Adult rats
      were irradiated with 35 or 350 Gy at the European Synchotron Research Facility
      (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam
      delivered to the right brain hemisphere only. The proteome of the frontal lobes
      were then analyzed using two-dimensional electrophoresis (2-DE) and mass
      spectrometry. RESULTS: HI resulted in proteomic responses indicative of
      tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI),
      and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect
      proteomic changes were indicative of reactive oxygen species mediated apoptosis;
      reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein
      (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also
      associated with neurodegeneration. However the bystander effect also increased
      heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of
      the neurological disorders characterized by the bystander effect proteome
      changes. CONCLUSIONS: These results indicate that the collective interaction of
      these MBI-induced bystander effect proteins and their mediation by HSP 71, may
      confer a protective effect which now warrants additional experimental attention.

PMID- 23004568
TI  - Activity assessment has little impact on caries parameters reduction in
      epidemiological surveys with preschool children.
AB  - OBJECTIVES: This study aimed to evaluate the magnitude of the reduction in caries
      parameters after inclusion of dental caries activity assessment, in an
      epidemiological survey of preschool children, involving cavitated and
      noncavitated caries lesions. METHODS: The survey was carried out in Santa Maria,
      Brazil, during the National Children's Vaccination Day, and 639 children aged
      between 12 months and 59 months were included. Fifteen examiners assessed the
      children based on the International Caries Detection and Assessment System
      (ICDAS) and additional lesion activity assessment criteria. The mean of decayed
      surfaces (d-s), the mean of decayed teeth (d-t), caries prevalence, and 95%
      confidence intervals were calculated, initially by classifying all lesions using
      the various thresholds defined by the ICDAS. Caries activity status was then
      evaluated, and inactive lesions were classified as sound in a secondary analysis;
      subsequently, the same caries parameters, at the same thresholds, were
      recalculated. The reduction in caries parameters and the number of children
      requiring assessment to change their classification from decayed to sound (number
      needed to be assessed) were also calculated. RESULTS: The majority of lesions
      were classified as active, mainly at cavitated thresholds. When activity was
      considered, values of all caries parameters decreased. This decrease was more
      evident at noncavitated thresholds. The number of children requiring assessment
      to change their classification from decayed to sound was <20 considering all
      lesions, but this value increased to approximately 100 when we included only
      cavitated lesions. CONCLUSIONS: The inclusion of activity assessment in caries
      epidemiological surveys has little impact on the d-s, d-t and prevalence of
      dental caries considering both noncavitated and cavitated lesions.

PMID- 23004569
TI  - A note on two-sample tests for comparing intra-individual genetic sequence
      diversity between populations.
AB  - Gilbert, Rossini, and Shankarappa (2005, Biometrics 61, 106-117) present four U
      statistic based tests to compare genetic diversity between different samples. The
      proposed tests improved upon previously used methods by accounting for the
      correlations in the data. We find, however, that the same correlations introduce
      an unacceptable bias in the sample estimators used for the variance and
      covariance of the inter-sequence genetic distances for modest sample sizes. Here,
      we compute unbiased estimators for these and test the resulting improvement using
      simulated data. We also show that, contrary to the claims in Gilbert et al., it
      is not always possible to apply the Welch-Satterthwaite approximate t-test, and
      we provide explicit formulas for the degrees of freedom to be used when, on the
      other hand, such approximation is indeed possible.

PMID- 23004570
TI  - When the circadian clock becomes a ticking time bomb.

PMID- 23004571
TI  - Noncovalent interactions in peri-substituted chalconium acenaphthene and
      naphthalene salts: a combined experimental, crystallographic, computational, and
      solid-state NMR study.
AB  - Twelve related monocation chalconium salts [{Nap(EPh)(E'Ph)Me}(+){CF(3)SO(3)}(-)]
      2-4, [{Acenap(Br)(EPh)Me}{CF(3)SO(3)}(-)] 5-7, and
      [{Acenap(EPh)(E'Ph)Me}(+){CF(3)SO(3)}(-)] 8-13 have been prepared and
      structurally characterized. For their synthesis naphthalene compounds
      [Nap(EPh)(E'Ph)] (Nap = naphthalene-1,8-diyl; E/E' = S, Se, Te) N2-N4 and
      associated acenaphthene derivatives [Acenap(X)(EPh)]/[Acenap(EPh)(E'Ph)] (Acenap
      = acenaphthene-5,6-diyl; E/E' = S, Se, Te; X = Br) A5-A13 were independently
      treated with a single molar equivalent of methyl trifluoromethanesulfonate
      (MeOTf). In addition, reaction of bis-tellurium compound A10 with 2 equiv of
      MeOTf afforded the doubly methylated dication salt
      [{Acenap(TePhMe)(2)}(2+){(CF(3)SO(3))(2)}(2-)}] 14. The distortion of the rigid
      naphthalene and acenaphthene backbone away from ideal was investigated in each
      case and correlated in general with the steric bulk of the interacting atoms
      located at the proximal peri positions. Naturally, introduction of the ethane
      linker in acenaphthene compounds increased the splay of the bay region compared
      with equivalent naphthalene derivatives resulting in greater peri distances. The
      conformation of the aromatic rings and subsequent location of p-type lone pairs
      has a significant impact on the geometry of the peri region, with anomalies in
      peri separations correlated to the ability of the frontier orbitals to take part
      in attractive or repulsive interactions. In all but one of the monocations a
      quasi-linear three-body C(Me)-E...Z (E = Te, Se, S; Z = Br/E) fragment provides
      an attractive component for the E...Z interaction. Density functional studies
      confirmed these interactions and suggested the onset of formation of three
      center, four-electron bonding under appropriate geometric conditions, becoming
      more prevalent as heavier congeners are introduced along the series. The
      increasingly large J values for Se-Se, Te-Se, and Te-Te coupling observed in the
      (77)Se and (125)Te NMR spectra for 1, 3, 4, 9, 10, and 13 give further evidence
      for the existence of a weakly attractive through-space interaction.

PMID- 23004572
TI  - Use of surface properties to control the growth and differentiation of mouse
      fetal liver stem/progenitor cell colonies.
AB  - Multilayers of poly-l-lysine/poly-l-glutamic acid (PLL/PLGA) were constructed by
      layer-by-layer deposition on an end-tethered cationic PLL brush film serving as
      an initial layer. Increasing the number of coupling layers increased the
      thickness and the hydration of the films, and decreased the films' shear modulus
      and serum adsorption. These films were used to culture primary mouse fetal liver
      cells. Fetal liver stem/progenitor cells (FLSPCs) were isolated and maintained on
      the PLGA-terminal PLL/PLGA surfaces, forming colonies with clear boundaries that
      were partially attached to the surface, with cross-sectional areas of ~500 to
      ~2500 MUm(2) after 2 days culture. Long-term studies showed that the cluster size
      of colonies slowly expanded and was correlated with the surface properties. For
      example, on the thicker films with shear modulus, G, less than 5 kPa, FLSPCs
      cluster size was constrained within a small distribution with less than 4000
      MUm(2) of projected area, whereas on the thinner films with G > 30 kPa, clusters
      were expanded and widely distributed, with projected areas over 4000 um(2).
      Immunostaining studies suggested that clusters with a small size maintained the
      self-renewal characteristics of stem cells, while the expanded clusters were
      clearly the results of spontaneous differentiation, exhibiting hepatocyte-like
      properties. On PLL-terminal t-(PLL/PLGA) films, which are less favorable for stem
      cell cultures than PLGA-terminal t-(PLL/PLGA) films, the cluster size
      distribution was also correlated with the film thickness, with more clusters of
      small size preserved on the thicker films. We observed that a soft, hydrated,
      serum-free surface could restrict the FLSPC expansion, resulting in self
      maintenance of FLSPC colonies.

PMID- 23004573
TI  - Cerebral blood flow, sympathetic nerve activity and stroke risk in obstructive
      sleep apnoea. Is there a direct link?
AB  - Obstructive sleep apnoea (OSA) is significantly associated with the risk of
      stroke, and this association is independent of other risk factors, including
      hypertension, atrial fibrillation and diabetes mellitus. Therefore, additional
      pathogenic mechanisms may exist, which contribute to the increased risk of
      stroke. OSA is characterized by prolonged sympathetic overactivity; however the
      role of the sympathetic nervous system in regulating cerebral circulation remains
      a matter of controversy. Converging data indicate that brain perfusion is
      significantly distorted in OSA, with reported decreases in cerebral blood flow as
      well as intermittent surges in blood pressure and cerebral blood flow velocity.
      Based on recent research, there is accumulating evidence that sympathetic nerve
      activity is an important element in brain protection against excessive increases
      in perfusion pressure during blood pressure surges and flow during rapid eye
      movement sleep. The aim of this article was to review: (i) the current
      physiological knowledge related to the role of the sympathetic system in the
      regulation of cerebral blood flow, (ii) how the influence of the sympathetic
      system on cerebral vessels is affected by apnoea (increased PaCO(2)) and (iii)
      the potential significance of the pathological sympathetic system/PaCO(2)
      interplay in OSA. Sympathetic system seems to be at least partially involved in
      pathogenesis of distorted haemodynamics and stroke in OSA patients. However,
      there are still several open questions that need to be addressed before the
      effective therapeutic strategies can be implemented.

PMID- 23004574
TI  - Insights from Pim1 structure for anti-cancer drug design.
AB  - INTRODUCTION: Pim1 is a unique, constitutively active serine/threonine kinase,
      and is a potent oncogene overexpressed in a range of hematologic malignancies and
      solid cancers. It functions as a signaling regulator in cell proliferation and
      survival pathways through substrate phosphorylation. More than 400 small
      molecular Pim1 inhibitors with IC(50)/Ki < 10 MUM have been registered in the
      ChEMBL. However, no drug targeting Pim1 has been launched at this present time.
      AREAS COVERED: The authors provide a review of Pim1 inhibitors from the viewpoint
      of the structural analysis of the Pim1-inhibitor complexes. PDB data and PubMed
      literature searches were performed. The inhibitors have been classified and
      summarized by their interactions with Pim1 residues, to facilitate desirable
      inhibitor design. EXPERT OPINION: To obtain a potent and selective Pim1 inhibitor
      as a lead compound, the authors propose the development of compounds which
      simultaneously interact with both the ATP binding site (Lys67, Glu121 and Phe49)
      and substrate binding residues (Asp128, Asp131 and Glu171). The development of
      Pim1 inhibitors could lead to new therapeutic options for a number of
      hematological malignancies and prostate cancer in the future.

PMID- 23004575
TI  - Alternative route to strong interaction: narrow Feshbach resonance.
AB  - We show that a narrow resonance produces strong interaction effects far beyond
      its width on the side of the resonance where the bound state has not been formed.
      This is due to a resonance structure of its phase shift, which shifts the phase
      of a large number of scattering states by pi before the bound state emerges. As a
      result, the magnitude of the interaction energy when approaching the resonance on
      the "upper" and "lower" branch from different side of the resonance is highly
      asymmetric, unlike their counterpart in wide resonances. Measurements of these
      effects are experimentally feasible.

PMID- 23004260
TI  - Search for gluinos in events with two same-sign leptons, jets, and missing
      transverse momentum with the ATLAS detector in pp collisions at sqrt[s]=7  TeV.
AB  - A search is presented for gluinos decaying via the supersymmetric partner of the
      top quark using events with two same-sign leptons, jets, and missing transverse
      momentum. The analysis is performed with 2.05  fb(-1) of integrated luminosity
      from pp collisions at sqrt[s]=7  TeV collected by the ATLAS detector at the LHC.
      No excess beyond the standard model expectation is observed, and exclusion limits
      are derived for simplified models where the gluino decays via the supersymmetric
      partner of the top quark and in the minimal supergravity and constrained minimal
      supersymmetric standard model framework. In those scenarios, gluino masses below
      550 GeV are excluded at 95% C.L. within the parameter space considered,
      significantly extending the coverage with respect to existing limits. Depending
      on the model parameters, gluino masses up to 750 GeV can also be excluded at 95%
      C.L.

PMID- 23004576
TI  - Nucleation in finite topological systems during continuous metastable quantum
      phase transitions.
AB  - Finite topological quantum systems can undergo continuous metastable quantum
      phase transitions to change their topological nature. Here we show how to
      nucleate the transition between ring currents and dark soliton states in a
      toroidally trapped Bose-Einstein condensate. An adiabatic passage to wind and
      unwind its phase is achieved by explicit global breaking of the rotational
      symmetry. This could be realized with current experimental technology.

PMID- 23004577
TI  - Quantum cost for sending entanglement.
AB  - Establishing quantum entanglement between two distant parties is an essential
      step of many protocols in quantum information processing. One possibility for
      providing long-distance entanglement is to create an entangled composite state
      within a lab and then physically send one subsystem to a distant lab. However, is
      this the "cheapest" way? Here, we investigate the minimal "cost" that is
      necessary for establishing a certain amount of entanglement between two distant
      parties. We prove that this cost is intrinsically quantum, and is specified by
      quantum correlations. Our results provide an optimal protocol for entanglement
      distribution and show that quantum correlations are the essential resource for
      this task.

PMID- 23004578
TI  - Optimal unambiguous discrimination of pure quantum states.
AB  - A complete geometric view is presented for the optimal unambiguous discrimination
      among N > 2 pure states. A single intuitive picture contains all aspects of the
      problem: linear independence of the states, positivity of the detection
      operators, and a graphic method for finding and classifying the optimal
      solutions. The method is illustrated on the example of three states. We show that
      the problem depends on the phases of the complex inner products only through an
      invariant combination, the Berry phase phi, and present complete analytical
      results for phi = 0 and phi = pi. The optimal solution exhibits full
      permutational symmetry and is single valued for a large range of parameters.
      However, for phi = 0 it can be bivalued: beyond a critical value of the
      parameters a second, less symmetric solution becomes optimal. The bifurcation is
      analogous to a second-order symmetry-breaking phase transition. We conclude with
      a discussion of the unambiguous discrimination of N > 3 states.

PMID- 23004581
TI  - Critical conditions for core-collapse supernovae.
AB  - The explosion of a core-collapse supernova can be approximated by the breakdown
      of steady-state solutions for accretion onto a proto-neutron star (PNS). We
      analytically show that as the neutrino luminosity exceeds a critical value L(c),
      the neutrinosphere pressure exceeds the hydrostatic limit even for an optimal
      shock radius R. This yields L(c) [proportionally] M(2)T(2) (with logarithmic
      corrections) and R [proportionally] M/T, in agreement with numerical results,
      where M and T are the PNS mass and neutrino temperature, respectively. The near
      critical flow can be approximated as a ballistic shell on top of an isothermal
      layer.

PMID- 23004579
TI  - Logarithmic oscillators: ideal Hamiltonian thermostats.
AB  - A logarithmic oscillator (in short, log-oscillator) behaves like an ideal
      thermostat because of its infinite heat capacity: When it weakly couples to
      another system, time averages of the system observables agree with ensemble
      averages from a Gibbs distribution with a temperature T that is given by the
      strength of the logarithmic potential. The resulting equations of motion are
      Hamiltonian and may be implemented not only in a computer but also with real
      world experiments, e.g., with cold atoms.

PMID- 23004580
TI  - Single temperature for Monte Carlo optimization on complex landscapes.
AB  - We propose a new strategy for Monte Carlo (MC) optimization on rugged
      multidimensional landscapes. The strategy is based on querying the statistical
      properties of the landscape in order to find the temperature at which the mean
      first passage time across the current region of the landscape is minimized. Thus,
      in contrast to other algorithms such as simulated annealing, we explicitly match
      the temperature schedule to the statistics of landscape irregularities. In cases
      where these statistics are approximately the same over the entire landscape or
      where nonlocal moves couple distant parts of the landscape, a single-temperature
      MC scheme outperforms any other MC algorithm with the same move set. We also find
      that in strongly anisotropic Coulomb spin glass and traveling salesman problems,
      the only relevant statistics (which we use to assign a single MC temperature) are
      those of irregularities in low-energy funnels. Our results may explain why
      protein folding is efficient at constant temperature.

PMID- 23004582
TI  - Clustering fossils from the early universe.
AB  - Many inflationary theories introduce new scalar, vector, or tensor degrees of
      freedom that may then affect the generation of primordial density perturbations.
      Here we show how to search a galaxy (or 21-cm) survey for the imprint of
      primordial scalar, vector, and tensor fields. These new fields induce local
      departures to an otherwise statistically isotropic two-point correlation
      function, or equivalently, nontrivial four-point correlation functions (or
      trispectra, in Fourier space), that can be decomposed into scalar, vector, and
      tensor components. We write down the optimal estimators for these various
      components and show how the sensitivity to these modes depends on the galaxy
      survey parameters. New probes of parity-violating early-Universe physics are also
      presented.

PMID- 23004583
TI  - Fermi surfaces in maximal gauged supergravity.
AB  - We obtain fermion fluctuation equations around extremal charged black hole
      geometries in maximal gauged supergravity in four and five dimensions, and we
      demonstrate that their solutions display Fermi surface singularities for the dual
      conformal field theories at finite chemical potential. The four-dimensional case
      is a massless charged fermion, while in five dimensions we find a massive charged
      fermion with a Pauli coupling. In both cases, the corresponding scaling exponent
      is less than one half, leading to non-Fermi liquid behavior with no stable
      quasiparticles, although some excitations have widths more than 10 times smaller
      than their excitation energy. In the five-dimensional case, both the Fermi
      momentum and the scaling exponent appear to have simple values, and a Luttinger
      calculation suggests that the gauginos may carry most of the charge of the black
      hole.

PMID- 23004584
TI  - Unified description of Nambu-Goldstone bosons without Lorentz invariance.
AB  - Using the effective Lagrangian approach, we clarify general issues about Nambu
      Goldstone bosons without Lorentz invariance. We show how to count their number
      and study their dispersion relations. Their number is less than the number of
      broken generators when some of them form canonically conjugate pairs. The pairing
      occurs when the generators have a nonzero expectation value of their commutator.
      For non-semi-simple algebras, central extensions are possible. The underlying
      geometry of the coset space in general is partially symplectic.

PMID- 23004587
TI  - How well do we know the neutron structure function?
AB  - We present a detailed analysis of the uncertainty in the neutron F(2n) structure
      function extracted from inclusive deuteron and proton deep-inelastic scattering
      data. The analysis includes experimental uncertainties as well as uncertainties
      associated with the deuteron wave function, nuclear smearing, and nucleon off
      shell corrections. Correctly accounting for the Q(2) dependence of the data and
      calculations and restricting the nuclear corrections to microscopic models of the
      deuteron, we find a significantly smaller uncertainty in the extracted
      F(2n)/F(2p) ratio than in previous analyses. In addition to yielding an improved
      extraction of the neutron structure function, this analysis also provides an
      important baseline that can be compared to future, model-independent extractions
      of neutron structure to examine nuclear medium effects in the deuteron.

PMID- 23004590
TI  - Directed flow at midrapidity in sqrt[S(NN)] = 2.76 TeV Pb + Pb collisions.
AB  - We analyze published data from the ALICE Collaboration in order to obtain the
      first extraction of the recently proposed rapidity-even directed flow observable
      v(1). An accounting of the correlation due to the conservation of transverse
      momentum restores the factorization seen by ALICE in all other Fourier harmonics
      and thus indicates that the remaining correlation gives a reliable measurement of
      directed flow. We then carry out the first viscous hydrodynamic calculation of
      directed flow, and show that it is less sensitive to viscosity than higher
      harmonics. This allows for a direct extraction of the dipole asymmetry of the
      initial state, providing a strict constraint on the nonequilibrium dynamics of
      the early-time system. A prediction is then made for v(1) in Au-Au collisions at
      RHIC.

PMID- 23004591
TI  - Nonsudden limits of heavy-ion induced knockout reactions.
AB  - We report on the single neutron and proton removal reactions from unstable nuclei
      with large asymmetry DeltaS = S(n)-S(p) at incident energies below 80
      MeV/nucleon. Strong nonsudden effects are observed in the case of deeply-bound
      nucleon removal. The corresponding parallel momentum distributions exhibit an
      abrupt cutoff at high momentum that corresponds to an energy threshold occurring
      when the incident energy per particle is of comparable magnitude to the nucleon
      separation energy. A large low-momentum tail is related to both dissipative
      processes and the dynamics of the nucleon removal process. New limits for the
      applicability of the sudden and eikonal approximations in nucleon knockout are
      given.

PMID- 23004589
TI  - Fluctuating glasma initial conditions and flow in heavy ion collisions.
AB  - We compute initial conditions in heavy ion collisions within the color glass
      condensate framework by combining the impact parameter dependent saturation model
      with the classical Yang-Mills description of initial Glasma fields. In addition
      to fluctuations of nucleon positions, this impact parameter dependent Glasma
      description includes quantum fluctuations of color charges on the length scale
      determined by the inverse nuclear saturation scale Q(s). The model naturally
      produces initial energy fluctuations that are described by a negative binomial
      distribution. The ratio of triangularity to eccentricity epsilon(3)/epsilon(2) is
      close to that in a model tuned to reproduce experimental flow data. We compare
      transverse momentum spectra and v(2,3,4)(p(T)) of pions from different models of
      initial conditions using relativistic viscous hydrodynamic evolution.

PMID- 23004592
TI  - Dynamic interference of photoelectrons produced by high-frequency laser pulses.
AB  - The ionization of an atom by a high-frequency intense laser pulse, where the
      energy of a single photon is sufficient to ionize the system, is investigated
      from first principles. It is shown that as a consequence of an ac Stark effect in
      the continuum, the energy of the photoelectron follows the envelope of the laser
      pulse. This is demonstrated to result in strong dynamic interference of the
      photoelectrons of the same kinetic energy emitted at different times. Numerically
      exact computations on the hydrogen atom demonstrate that the dynamic interference
      spectacularly modifies the photoionization process and is prominently manifested
      in the photoelectron spectrum by the appearance of a distinct multipeak pattern.
      The general theory is well approximated by explicit analytical expressions that
      allow for a transparent understanding of the discovered phenomena and for making
      predictions on the dependence of the measured spectrum on the pulse.

PMID- 23004593
TI  - Finding density functionals with machine learning.
AB  - Machine learning is used to approximate density functionals. For the model
      problem of the kinetic energy of noninteracting fermions in 1D, mean absolute
      errors below 1 kcal/mol on test densities similar to the training set are reached
      with fewer than 100 training densities. A predictor identifies if a test density
      is within the interpolation region. Via principal component analysis, a projected
      functional derivative finds highly accurate self-consistent densities. The
      challenges for application of our method to real electronic structure problems
      are discussed.

PMID- 23004594
TI  - Evidence for chirped Auger-electron emission.
AB  - Auger decay carries valuable information about the electronic structure and
      dynamics of atoms, molecules, and solids. Here we furnish evidence that under
      certain conditions Auger electrons are subject to an energetic chirp. The effect
      is disclosed in time-resolved streaking experiments on the Xe NOO and Kr MNN
      Auger decay using extreme-ultraviolet pulses from the free-electron laser in
      Hamburg as well as from a high-order harmonic laser source. The origin of this
      effect is found to be an exchange of energy between the Auger electron and an
      earlier emitted correlated photoelectron. The observed time-dependent spectral
      modulations are understood within an analytical model and confirmed by extensive
      computer simulations.

PMID- 23004595
TI  - Two-photon cooperative absorption in colliding cold Na atoms.
AB  - Two-photon cooperative absorption is common in solid-state physics. In a sample
      of trapped cold atoms, this effect may open up new possibilities for the study of
      nonlinear effects. The experiment described herein starts with two colliding Na
      atoms in the S hyperfine ground state. The pair absorb two photons, resulting in
      both a P(1/2) and a P(3/2) atom. This excitation is observed by ionization using
      an external light source. A simple model that considers only dipole-dipole
      interactions between the atoms allows us to understand the basic features
      observed in the experimental results. Both the pair of generated atoms and the
      photons originating from their decay are correlated and may have interesting
      applications that remain to be explored.

PMID- 23004596
TI  - Improved electronic excitation energies from shape-corrected semilocal Kohn-Sham
      potentials.
AB  - We propose a general method for obtaining accurate valence and Rydberg excitation
      energies from standard density-functional approximations in adiabatic linear
      response time-dependent density-functional theory. The method consists in
      modeling the sum of Hartree (Coulomb) and exchange-correlation potentials,
      v(HXC)(r), by the Hartree-exchange-correlation potential of the corresponding
      partially ionized system in which a fraction of electron charge (delta = 0.15 to
      0.30, depending on the functional) is removed from the highest occupied Kohn-Sham
      orbital level. The model potential is less repulsive and closer to exact in
      valence and near asymptotic regions, so it yields more accurate Kohn-Sham
      orbitals and orbital eigenvalues. By applying this scheme to conventional local,
      semilocal, and hybrid density-functional approximations, we improve their
      accuracy for Rydberg excitations by almost an order of magnitude without
      sacrificing the already good performance for valence transitions.

PMID- 23004598
TI  - Direct observation of the hyperfine transition of ground-state positronium.
AB  - We report the first direct measurement of the hyperfine transition of the ground
      state positronium. The hyperfine structure between ortho-positronium and para
      positronium is about 203 GHz. We develop a new optical system to accumulate about
      10 kW power using a gyrotron, a mode converter, and a Fabry-Perot cavity. The
      hyperfine transition has been observed with a significance of 5.4 standard
      deviations. The transition probability is measured to be A = 3.1(-1.2)(+1.6) *
      10(-8) s(-1) for the first time, which is in good agreement with the theoretical
      value of 3.37 * 10(-8) s(-1).

PMID- 23004597
TI  - Transient X-ray fragmentation: probing a prototypical photoinduced ring opening.
AB  - We report the first study of UV-induced photoisomerization probed via core
      ionization by an x-ray laser. We investigated x-ray ionization and fragmentation
      of the cyclohexadiene-hexatriene system at 850 eV during the ring opening. We
      find that the ion-fragmentation patterns evolve over a picosecond, reflecting a
      change in the state of excitation and the molecular geometry: the average kinetic
      energy per ion fragment and H(+)-ion count increase as the ring opens and the
      molecule elongates. We discuss new opportunities for molecular photophysics
      created by optical pump x-ray probe experiments.

PMID- 23004599
TI  - Persistent molecular superfluid response in doped para-hydrogen clusters.
AB  - Direct observation of superfluid response in para-hydrogen (p-H(2)) remains a
      challenge because of the need for a probe that would not induce localization and
      a resultant reduction in superfluid fraction. Earlier work [H. Li, R. J. Le Roy,
      P.-N. Roy, and A. R. W. McKellar, Phys. Rev. Lett. 105, 133401 (2010)] has shown
      that carbon dioxide can probe the effective inertia of p-H(2) although larger
      clusters show a lower superfluid response due to localization. It is shown here
      that the lighter carbon monoxide probe molecule allows one to measure the
      effective inertia of p-H(2) clusters while maintaining a maximum superfluid
      response with respect to dopant rotation. Microwave spectroscopy and a
      theoretical analysis based on Feynman path-integral simulations are used to
      support this conclusion.

PMID- 23004600
TI  - Ancilla-assisted calibration of a measuring apparatus.
AB  - A quantum measurement can be described by a set of matrices, one for each
      possible outcome, which represents the positive operator-valued measure (POVM) of
      the sensor. Efficient protocols of POVM extraction for arbitrary sensors are
      required. We present the first experimental POVM reconstruction that takes
      explicit advantage of a quantum resource, i.e., nonclassical correlations with an
      ancillary state. A POVM of a photon-number-resolving detector is reconstructed by
      using strong quantum correlations of twin beams generated by parametric down
      conversion. Our reconstruction method is more statistically robust than POVM
      reconstruction methods that use classical input states.

PMID- 23004601
TI  - Negative-frequency resonant radiation.
AB  - Optical solitons or solitonlike states shed light to blueshifted frequencies
      through a resonant emission process. We predict a mechanism by which a second
      propagating mode is generated. This mode, called negative resonant radiation,
      originates from the coupling of the soliton mode to the negative-frequency branch
      of the dispersion relation. Measurements in both bulk media and photonic-crystal
      fibers confirm our predictions.

PMID- 23004602
TI  - Local chirality of optical resonances in ultrasmall resonators.
AB  - In wavelength-scale cavities with chiral-symmetric geometry, wave optical effects
      can introduce local chirality, that is, a spatial separation of the clockwise and
      counterclockwise propagating resonant modes. We show that this local chirality
      results in unidirectional lasing emission in the far field. In the presence of a
      waveguide, the local chirality also allows for directional evanescent coupling of
      the lasing modes, and the output direction can be varied by selecting the
      coupling position along the cavity boundary. Our results demonstrate that the
      local chirality of optical resonances can be utilized to control the output
      directionality and enhance the collection efficiency of emission from ultrasmall
      resonators.

PMID- 23004603
TI  - Ultrafast polarization shaping with Fano plasmonic crystals.
AB  - Femtosecond-scale polarization state shaping is experimentally found in optical
      response of a plasmonic nanograting by means of time-resolved Stokes polarimetry.
      Simultaneous measurements of the Stokes parameters as a function of time reveal a
      remarkable alteration of the polarization state inside a single femtosecond pulse
      reflected from a plasmonic crystal due to the excitation of time-delayed
      polarization-sensitive surface plasmons with a highly birefringent Fano-type
      spectral profile. Time-dependent depolarization, indicating the sub-130
      femtosecond polarization change inside the pulse, is experimentally found and
      described within an analytical model which predicts the fivefold enhancement of
      the polarization conversion effect with the use of a narrower time gate.

PMID- 23004604
TI  - Detection of the ultranarrow temporal correlation of twin beams via sum-frequency
      generation.
AB  - We demonstrate the ultranarrow temporal correlation (6 fs full width half
      maximum) of twin beams generated by parametric down-conversion by using its
      reverse process, i.e., sum-frequency generation. The result relies on an
      achromatic imaging of a huge bandwidth of twin beams and on a careful control of
      their spatial degrees of freedom. The detrimental effects of spatial filtering
      and imperfect imaging are shown, along with the theoretical model used to
      describe the results.

PMID- 23004605
TI  - Taylor-Couette instability in anisotropic clay suspensions measured using small
      angle X-ray scattering.
AB  - In this Letter, we propose an original and novel experimental method to
      characterize both the onset and morphology of Taylor-Couette instability
      occurring in a non-Newtonian cylindrical Couette flow. Using synchrotron-based
      rheological small angle x-ray scattering experiments, we jointly investigate the
      shear-thinning behavior of natural swelling clays suspensions and the associated
      anisotropy developing in such media. Combined with a linear stability analysis
      for power law fluids, a destabilizing effect is shown both numerically and
      experimentally and the vortices morphology is found to be dependent on the fluid
      index. Still, the strong destabilizing effect and large vortex size can not be
      assigned to shear-thinning only, which clearly evidences the impact of medium
      anisotropy on Taylor-Couette instability.

PMID- 23004606
TI  - Absence of Debye sheaths due to secondary electron emission.
AB  - A bounded plasma where the hot electrons impacting the walls produce more than
      one secondary on average is studied via particle-in-cell simulation. It is found
      that no classical Debye sheath or space-charge-limited sheath exists. Ions are
      not drawn to the walls and electrons are not repelled. Hence the unconfined
      plasma electrons travel unobstructed to the walls, causing extreme particle and
      energy fluxes. Each wall has a positive charge, forming a small potential barrier
      or "inverse sheath" that pulls some secondaries back to the wall to maintain the
      zero current condition.

PMID- 23004607
TI  - Oscillation spectrum of a magnetized strongly coupled one-component plasma.
AB  - A first-principles study of the collective oscillation spectrum of a strongly
      correlated one-component plasma in a strong magnetic field is presented. The
      spectrum consists of six fundamental modes that are found to be in good agreement
      with results from the quasilocalized charge approximation. At high frequencies,
      additional modes are observed that include Bernstein-type oscillations and their
      transverse counterparts, which are of importance for the high-frequency optical
      and transport properties of these plasmas.

PMID- 23004608
TI  - Observation of lobes near the X point in resonant magnetic perturbation
      experiments on MAST.
AB  - The application of nonaxisymmetric resonant magnetic perturbations (RMPs) with a
      toroidal mode number n = 6 in the MAST tokamak produces a significant reduction
      in plasma energy loss associated with type-I edge localized modes (ELMs), the
      first such observation with n > 3. During the ELM mitigated stage clear lobe
      structures are observed in visible-light imaging of the X-point region. These
      lobes or manifold structures, that were predicted previously, have been observed
      for the first time in a range of discharges and their appearance is correlated
      with the effect of RMPs on the plasma; i.e., they only appear above a threshold
      when a density pump out is observed or when the ELM frequency is increased. They
      appear to be correlated with the RMPs penetrating the plasma and may be important
      in explaining why the ELM frequency increases. The number and location of the
      structures observed can be well described using vacuum modeling. Differences in
      radial extent and poloidal width from vacuum modeling are likely to be due to a
      combination of transport effects and plasma screening.

PMID- 23004586
TI  - First observation of the decay B(c)+ -> J/psipi(+) pi- pi+.
AB  - The decay B(c)(+) -> J/psipi(+) pi(-) pi(+) is observed for the first time, using
      0.8 fb(-1) of pp collisions at sqrt[s] = 7 TeV collected by the LHCb experiment.
      The ratio of branching fractions B(B(c)(+) -> J/psipi(+) pi(-) pi(+))/B(B(c)(+)
      >J/psipi^{+}) is measured to be 2.41 +/- 0.30 +/- 0.33, where the first
      uncertainty is statistical and the second is systematic. The result is in
      agreement with theoretical predictions.

PMID- 23004609
TI  - Waveform-controlled terahertz radiation from the air filament produced by few
      cycle laser pulses.
AB  - Waveform-controlled terahertz (THz) radiation is of great importance due to its
      potential application in THz sensing and coherent control of quantum systems. We
      demonstrated a novel scheme to generate waveform-controlled THz radiation from
      air plasma produced when carrier-envelope-phase (CEP) stabilized few-cycle laser
      pulses undergo filamentation in ambient air. We launched CEP-stabilized 10 fs
      long (~1.7 optical cycles) laser pulses at 1.8 MUm into air and found that the
      generated THz waveform can be controlled by varying the filament length and the
      CEP of driving laser pulses. Calculations using the photocurrent model and
      including the propagation effects well reproduce the experimental results, and
      the origins of various phase shifts in the filament are elucidated.

PMID- 23004610
TI  - Secondary magnetic islands generated by the Kelvin-Helmholtz instability in a
      reconnecting current sheet.
AB  - Magnetic islands or flux ropes produced by magnetic reconnection have been
      observed on the magnetopause, in the magnetotail, and in coronal current sheets.
      Particle-in-cell simulations of magnetic reconnection with a guide field produce
      elongated electron current layers that spontaneously produce secondary islands.
      Here, we explore the seed mechanism that gives birth to these islands. The most
      commonly suggested theory for island formation is the tearing instability. We
      demonstrate that in our simulations these structures typically start out, not as
      magnetic islands, but as electron flow vortices within the electron current
      sheet. When some of these vortices first form, they do not coincide with closed
      magnetic field lines, as would be the case if they were islands. Only after they
      have grown larger than the electron skin depth do they couple to the magnetic
      field and seed the growth of finite-sized islands. The streaming of electrons
      along the magnetic separatrix produces the flow shear necessary to drive an
      electron Kelvin-Helmholtz instability and produce the initial vortices. The
      conditions under which this instability is the dominant mechanism for seeding
      magnetic islands are explored.

PMID- 23004611
TI  - First measurements of Rayleigh-Taylor-induced magnetic fields in laser-produced
      plasmas.
AB  - The first experimental demonstration of Rayleigh-Taylor-induced magnetic fields
      due to the Biermann battery effect has been made. Experiments with laser
      irradiated plastic foils were performed to investigate these illusive fields
      using a monoenergetic proton radiography system. Path-integrated B field strength
      measurements were inferred from radiographs and found to increase from 10 to 100
      T MUm during the linear growth phase for 120 MUm perturbations. Proton fluence
      modulations were corrected for Coulomb scattering using measured areal density
      profiles from x-ray radiographs.

PMID- 23004612
TI  - Experimental observation of electron-temperature-gradient turbulence in a
      laboratory plasma.
AB  - We report the observation of electron-temperature-gradient (ETG) driven
      turbulence in the laboratory plasma of a large volume plasma device. The removal
      of unutilized primary ionizing and nonthermal electrons from uniform density
      plasma and the imposition and control of the gradient in the electron temperature
      (T[Symbol: see text] T(e)) are all achieved by placing a large (2 m diameter)
      magnetic electron energy filter in the middle of the device. In the dressed
      plasma, the observed ETG turbulence in the lower hybrid range of frequencies nu =
      (1-80 kHz) is characterized by a broadband with a power law. The mean wave number
      k perpendicular rho(e) = (0.1-0.2) satisfies the condition k perpendicular rho(e)
      <= 1, where rho(e) is the electron Larmor radius.

PMID- 23004614
TI  - Superfluid state of repulsively interacting three-component fermionic atoms in
      optical lattices.
AB  - We investigate the superfluid state of repulsively interacting three-component
      (color) fermionic atoms in optical lattices. When the anisotropy of the three
      repulsive interactions is strong, atoms of two of the three colors form Cooper
      pairs and atoms of the third color remain a Fermi liquid. An effective attractive
      interaction is induced by density fluctuations of the third-color atoms. This
      superfluid state is stable against changes in filling close to half filling. We
      determine the phase diagrams in terms of temperature, filling, and the anisotropy
      of the repulsive interactions.

PMID- 23004613
TI  - Field reversed configuration confinement enhancement through edge biasing and
      neutral beam injection.
AB  - Field reversed configurations (FRCs) with high confinement are obtained in the C
      2 device by combining plasma gun edge biasing and neutral beam injection. The
      plasma gun creates an inward radial electric field that counters the usual FRC
      spin-up. The n = 2 rotational instability is stabilized without applying
      quadrupole magnetic fields. The FRCs are nearly axisymmetric, which enables fast
      ion confinement. The plasma gun also produces E * B shear in the FRC edge layer,
      which may explain the observed improved particle transport. The FRC confinement
      times are improved by factors 2 to 4, and the plasma lifetimes are extended from
      1 to up to 4 ms.

PMID- 23004615
TI  - Dipolar gases in coupled one-dimensional lattices.
AB  - We consider dipolar bosons in two tubes of one-dimensional lattices, where the
      dipoles are aligned to be maximally repulsive and the particle filling fraction
      is the same in each tube. In the classical limit of zero intersite hopping, the
      particles arrange themselves into an ordered crystal for any rational filling
      fraction, forming a complete devil's staircase like in the single tube case.
      Turning on hopping within each tube then gives rise to a competition between the
      crystalline Mott phases and a liquid of defects or solitons. However, for the two
      tube case, we find that solitons from different tubes can bind into pairs for
      certain topologies of the filling fraction. This provides an intriguing example
      of pairing that is purely driven by correlations close to a Mott insulator.

PMID- 23004616
TI  - Detecting chiral edge states in the Hofstadter optical lattice.
AB  - We propose a realistic scheme to detect topological edge states in an optical
      lattice subjected to a synthetic magnetic field, based on a generalization of
      Bragg spectroscopy sensitive to angular momentum. We demonstrate that using a
      well-designed laser probe, the Bragg spectra provide an unambiguous signature of
      the topological edge states that establishes their chiral nature. This signature
      is present for a variety of boundaries, from a hard wall to a smooth harmonic
      potential added on top of the optical lattice. Experimentally, the Bragg signal
      should be very weak. To make it detectable, we introduce a "shelving method,"
      based on Raman transitions, which transfers angular momentum and changes the
      internal atomic state simultaneously. This scheme allows us to detect the weak
      signal from the selected edge states on a dark background, and drastically
      improves the detectivity. It also leads to the possibility to directly visualize
      the topological edge states, using in situ imaging, offering a unique and
      instructive view on topological insulating phases.

PMID- 23004618
TI  - Stability and strength of transition-metal tetraborides and triborides.
AB  - Using density functional theory, we show that the long-believed transition-metal
      tetraborides (TB(4)) of tungsten and molybdenum are in fact triborides (TB(3)).
      This finding is supported by thermodynamic, mechanical, and phonon instabilities
      of TB(4), and it challenges the previously proposed origin of superhardness of
      these compounds and the predictability of the generally used hardness model.
      Theoretical calculations for the newly identified stable TB(3) structure
      correctly reproduce their structural and mechanical properties, as well as the
      experimental x-ray diffraction pattern. However, the relatively low shear moduli
      and strengths suggest that TB(3) cannot be intrinsically stronger than c-BN. The
      origin of the lattice instability of TB(3) under large shear strain that occurs
      at the atomic level during plastic deformation can be attributed to valence
      charge depletion between boron and metal atoms, which enables easy sliding of
      boron layers between the metal ones.

PMID- 23004617
TI  - Disentangling neighbors and extended range density oscillations in monatomic
      amorphous semiconductors.
AB  - High energy x-ray diffraction measurements of pure amorphous Ge were made and its
      radial distribution function (RDF) was determined at high resolution, revealing
      new information on the atomic structure of amorphous semiconductors. Fine
      structure in the second peak in the RDF provides evidence that a fraction of
      third neighbors are closer than some second neighbors; taking this into account
      leads to a narrow distribution of tetrahedral bond angles, (8.5 +/- 0.1) degrees
      . A small peak which appears near 5 A upon thermal annealing shows that some
      ordering in the dihedral bond-angle distribution takes place during structural
      relaxation. Extended range order is detected (in both a-Ge and a-Si) which
      persists to beyond 20 A, and both the periodicity and its decay length increase
      upon thermal annealing. Previously, the effect of structural relaxation was only
      detected at intermediate range, involving reduced tetrahedral bond-angle
      distortions. These results enhance our understanding of the atomic order in
      continuous random networks and place significantly more stringent requirements on
      computer models intending to describe these networks, or their alternatives which
      attempt to describe the structure in terms of an arrangement of paracrystals.

PMID- 23004619
TI  - Giant optical nonlinearity of graphene in a strong magnetic field.
AB  - We calculate the nonlinear optical response of graphene in strong magnetic and
      optical fields, using a quantum-mechanical density-matrix formalism. We show that
      graphene in a magnetic field possesses a giant mid- or far-infrared optical
      nonlinearity, perhaps the highest among known materials. The high nonlinearity
      originates from unique electronic properties and selection rules near the Dirac
      point. As a result, even one monolayer of graphene gives rise to an appreciable
      nonlinear frequency conversion efficiency for incident infrared radiation.

PMID- 23004620
TI  - Creep in colloidal glasses.
AB  - We investigate the nonlinear response to shear stress of a colloidal hard-sphere
      glass, identifying several regimes depending on time, sample age, and the
      magnitude of applied stress. This emphasizes a connection between stress-imposed
      deformation of soft and hard matter, in particular, colloidal and metallic
      systems. A generalized Maxwell model rationalizes logarithmic creep for long
      times and low stresses. We identify diverging time scales approaching a critical
      yield stress. At intermediate times, strong aging effects are seen, which we link
      to a stress overshoot seen in stress-strain curves.

PMID- 23004621
TI  - Metastable crystalline AuGe catalysts formed during isothermal germanium nanowire
      growth.
AB  - We observe the formation of metastable AuGe phases without quenching, during
      strictly isothermal nucleation and growth of Ge nanowires, using video-rate
      lattice-resolved environmental transmission electron microscopy. We explain the
      unexpected formation of these phases through a novel pathway involving changes in
      composition rather than temperature. The metastable catalyst has important
      implications for nanowire growth, and more broadly, the isothermal process
      provides both a new approach to growing and studying metastable phases, and a new
      perspective on their formation.

PMID- 23004622
TI  - Generalized scaling theory for critical phenomena including essential
      singularities and infinite dimensionality.
AB  - We propose a generic scaling theory for critical phenomena that includes power
      law and essential singularities in finite and infinite dimensional systems. In
      addition, we clarify its validity by analyzing the Potts model in a simple
      hierarchical network, where a saddle-node bifurcation of the renormalization
      group fixed point governs the essential singularity.

PMID- 23004623
TI  - Experimental validation of the interfacial form of the Wiedemann-Franz law.
AB  - The thermal conductivity of four Pd/Ir metal multilayers of total thickness 390
      nm with 40, 80, 120, and 200 Pd/Ir interfaces are measured at temperatures
      between 78 and 295 K using time-domain thermoreflectance. The thermal interface
      conductance G of the Pd/Ir interface is derived from the differences in thermal
      conductivity between the multilayers. A comparison of G to previously reported
      data for the electronic specific resistance of the Pd/Ir interface at 4 K
      supports the validity of the interfacial form of the Wiedemann-Franz law. The
      Lorenz number deduced from this comparison is within 10% of the Sommerfeld value
      at all temperatures, well within the experimental uncertainties of ~ 20%.

PMID- 23004624
TI  - Anomalous potential dependence in homoepitaxial Cu(001) electrodeposition: an in
      situ surface x-ray diffraction study.
AB  - Homoepitaxial Cu electrodeposition on Cu(001) in chloride-containing electrolyte
      was studied by time-resolved in situ surface x-ray diffraction at growth rates up
      to 38 ML/ min. With increasing Cu electrode potential, transitions from step-flow
      to layer-by-layer and then to multilayer growth are observed. This potential
      dependence is opposite to that expected theoretically and found experimentally
      for the Au(001) homoepitaxial electrodeposition [K. Krug et al., Phys. Rev. Lett.
      96, 246101 (2006)]. The anomalous behavior is rationalized by a decisive
      influence of the ordered c(2 * 2)-Cl adlayer on the surface energy landscape,
      specifically on the effective change in dipole moment during adatom diffusion.

PMID- 23004625
TI  - Self-limiting evolution of seeded quantum wires and dots on patterned substrates.
AB  - Extensive experimental data and an accompanying theoretical model are presented
      for the self-limiting profiles and Ga segregation on patterned GaAs(111)B
      substrates during metalorganic vapor-phase epitaxy of Al(x)Ga(1-x)As. Self
      limiting widths and segregation of Ga produce quantum dots along the base of
      pyramidal recesses bounded by (111)A planes and quantum wires along the vertical
      axis of the template, respectively. Coupled reaction-diffusion equations for
      precursor and adatom kinetics reproduce the measured concentration and
      temperature dependence of the self-limiting width and segregation. Our model can
      be extended to other patterned systems, providing a new paradigm for predicting
      the morphology of surface nanostructures and inferring their quantum optical
      properties.

PMID- 23004626
TI  - Molecular fingerprints in the electronic properties of crystalline organic
      semiconductors: from experiment to theory.
AB  - By comparing photoemission spectroscopy with a nonperturbative dynamical mean
      field theory extension to many-body ab initio calculations, we show in the
      prominent case of pentacene crystals that an excellent agreement with experiment
      for the bandwidth, dispersion, and lifetime of the hole carrier bands can be
      achieved in organic semiconductors, provided that one properly accounts for the
      coupling to molecular vibrational modes and the presence of disorder. Our
      findings rationalize the growing experimental evidence that even the best band
      structure theories based on a many-body treatment of electronic interactions
      cannot reproduce the experimental photoemission data in this important class of
      materials.

PMID- 23004627
TI  - Vanadium dioxide: a Peierls-Mott insulator stable against disorder.
AB  - Vanadium dioxide undergoes a first order metal-insulator transition at 340 K. In
      this Letter, we develop and carry out state-of-the-art linear scaling density
      functional theory calculations refined with nonlocal dynamical mean-field theory.
      We identify a complex mechanism, a Peierls-assisted orbital selection Mott
      instability, which is responsible for the insulating M(1) phase, and which
      furthermore survives a moderate degree of disorder.

PMID- 23004628
TI  - Range-separated approach to the RPA correlation applied to the van der Waals Bond
      and to diffusion of defects.
AB  - The random-phase approximation (RPA) is a promising approximation to the exchange
      correlation energy of density functional theory, since it contains the van der
      Waals (vdW) interaction and yields a potential with the correct band gap.
      However, its calculation is computationally very demanding. We apply a range
      separation concept to RPA and demonstrate how it drastically speeds up the
      calculations without loss of accuracy. The scheme is then successfully applied to
      a layered system subjected to weak vdW attraction and is used to address the
      controversy of the self-diffusion in silicon. We calculate the formation and
      migration energies of self-interstitials and vacancies taking into account atomic
      relaxations. The obtained activation energies deviate significantly from the
      earlier calculations and challenge some of the experimental interpretations: the
      diffusion of vacancies and interstitials has almost the same activation energy.

PMID- 23004629
TI  - Strong quantum interference in strongly disordered bosonic insulators.
AB  - We study the variable-range hopping of bosons in an array of sites with short
      range interactions and a large characteristic coordination number. The latter
      leads to strong quantum interference phenomena yet allows for their analytical
      study. We develop a functional renormalization-group scheme that repeatedly
      eliminates high-energy sites properly renormalizing the tunneling between the low
      energy ones. Using this approach we determine the temperature and magnetic field
      dependence of the hopping conductivity and find a large positive
      magnetoresistance. With increasing magnetic field the behavior of the
      conductivity crossovers from the Mott's law to an activational behavior with the
      activation gap proportional to the magnetic field.

PMID- 23004630
TI  - Piezoresistance in silicon at uniaxial compressive stresses up to 3 GPa.
AB  - The room-temperature longitudinal piezoresistance of n-type and p-type
      crystalline silicon along selected crystal axes is investigated under uniaxial
      compressive stresses up to 3 GPa. While the conductance (G) of n-type silicon
      eventually saturates at ~ 45% of its zero-stress value (G(0)) in accordance with
      the charge transfer model, in p-type material G/G(0) increases above a predicted
      limit of ~ 4.5 without any significant saturation, even at 3 GPa. Calculation of
      G/G(0) using ab initio density functional theory reveals that neither G nor the
      mobility, when properly averaged over the hole distribution, saturate at stresses
      lower than 3 GPa. The lack of saturation has important consequences for strained
      silicon technologies.

PMID- 23004631
TI  - Quantum coherence engineering in the integer quantum Hall regime.
AB  - We present an experiment where the quantum coherence in the edge states of the
      integer quantum Hall regime is tuned with a decoupling gate. The coherence length
      is determined by measuring the visibility of quantum interferences in a Mach
      Zehnder interferometer as a function of temperature, in the quantum Hall regime
      at a filling factor 2. The temperature dependence of the coherence length can be
      varied by a factor of 2. The strengthening of the phase coherence at finite
      temperature is shown to arise from a reduction of the coupling between
      copropagating edge states. This opens the way for a strong improvement of the
      phase coherence of quantum Hall systems. The decoupling gate also allows us to
      investigate how interedge state coupling influences the quantum interferences'
      dependence on the injection bias. We find that the finite bias visibility can be
      decomposed into two contributions: a Gaussian envelope which is surprisingly
      insensitive to the coupling, and a beating component which, on the contrary, is
      strongly affected by the coupling.

PMID- 23004632
TI  - Coulomb oscillations in antidots in the integer and fractional quantum Hall
      regimes.
AB  - We report measurements of resistance oscillations in micron-scale antidots in
      both the integer and fractional quantum Hall regimes. In the integer regime, we
      conclude that oscillations are of the Coulomb type from the scaling of magnetic
      field period with the number of edges bound to the antidot. Based on both gate
      voltage and field periods, we find at filling factor nu = 2 a tunneling charge of
      e and two charged edges. Generalizing this picture to the fractional regime, we
      find (again, based on field and gate-voltage periods) at nu = 2/3 a tunneling
      charge of (2/3)e and a single charged edge.

PMID- 23004633
TI  - Fabry-Perot interferometry with fractional charges.
AB  - Resistance oscillations in electronic Fabry-Perot interferometers near fractional
      quantum Hall (FQH) filling factors 1/3, 2/3, 4/3, and 5/3 in the constrictions
      are compared to those near integer quantum Hall (IQH) filling factors in the same
      devices and at the same gate voltages. Two-dimensional plots of resistance versus
      gate voltage and magnetic field indicate that all oscillations are Coulomb
      dominated. A charging-model analysis of gate-voltage periods yields an effective
      tunneling charge e* ~ e/3 for all FQH states and e* ~ e for IQH states.
      Temperature decay of the oscillations appears exponential, qualitatively
      consistent with a recent prediction, and the surprising filling-factor dependence
      of the associated energy scale may shed light on edge structure.

PMID- 23004634
TI  - Dephasing by a zero-temperature detector and the Friedel sum rule.
AB  - Detecting the passage of an interfering particle through one of the
      interferometer's arms, known as "which path" measurement, gives rise to
      interference visibility degradation (dephasing). Here, we consider a detector at
      equilibrium. At finite temperature, dephasing is caused by thermal fluctuations
      of the detector. More interestingly, in the zero-temperature limit, equilibrium
      quantum fluctuations of the detector give rise to dephasing of the out-of
      equilibrium interferometer. This dephasing is a manifestation of an orthogonality
      catastrophe, which differs qualitatively from Anderson's. Its magnitude is
      directly related to the Friedel sum rule.

PMID- 23004635
TI  - Evaluation of ranks of real space and particle entanglement spectra for large
      systems.
AB  - We devise a way to calculate the dimensions of symmetry sectors appearing in the
      particle entanglement spectrum (PES) and real space entanglement spectrum (RSES)
      of multiparticle systems from their real space wave functions. We first note that
      these ranks in the entanglement spectra equal the dimensions of spaces of wave
      functions with a number of particles fixed. This also yields equality of the
      multiplicities in the PES and the RSES. Our technique allows numerical
      calculations for much larger systems than were previously feasible. For somewhat
      smaller systems, we can find approximate entanglement energies as well as
      multiplicities. We illustrate the method with results on the RSES and PES
      multiplicities for integer quantum Hall states, Laughlin and Jain composite
      fermion states, and for the Moore-Read state at filling nu = 5/2 for system sizes
      up to 70 particles.

PMID- 23004636
TI  - Model wave functions for the collective modes and the magnetoroton theory of the
      fractional quantum Hall effect.
AB  - We construct model wave functions for the collective modes of fractional quantum
      Hall systems. The wave functions are expressed in terms of symmetric polynomials
      characterized by a root partition that defines a "squeezed" basis, and show
      excellent agreement with exact diagonalization results for finite systems. In the
      long wavelength limit, we prove that the model wave functions are identical to
      those predicted by the single-mode approximation, leading to intriguing
      interpretations of the collective modes from the perspective of the ground-state
      guiding-center metric.

PMID- 23004637
TI  - Coherent phonon coupling to individual Bloch states in photoexcited bismuth.
AB  - We investigate the temporal evolution of the electronic states at the bismuth
      (111) surface by means of time- and angle-resolved photoelectron spectroscopy.
      The binding energy of bulklike bands oscillates with the frequency of the A(1g)
      phonon mode, whereas surface states are insensitive to the coherent displacement
      of the lattice. A strong dependence of the oscillation amplitude on the
      electronic wave vector is correctly reproduced by ab initio calculations of
      electron-phonon coupling. Besides these oscillations, all the electronic states
      also display a photoinduced shift towards higher binding energy whose dynamics
      follows the evolution of the electronic temperature.

PMID- 23004638
TI  - Fractional quantum Hall effect of lattice bosons near commensurate flux.
AB  - We study interacting bosons on a lattice in a magnetic field. When the number of
      flux quanta per plaquette is close to a rational fraction, the low-energy physics
      is mapped to a multispecies continuum model: bosons in the lowest Landau level
      where each boson is given an internal degree of freedom, or pseudospin. We find
      that the interaction potential between the bosons involves terms that do not
      conserve pseudospin, corresponding to umklapp processes, which in some cases can
      also be seen as BCS-type pairing terms. We argue that in experimentally realistic
      regimes for bosonic atoms in optical lattices with synthetic magnetic fields,
      these terms are crucial for determining the nature of allowed ground states. In
      particular, we show numerically that certain paired wave functions related to the
      Moore-Read Pfaffian state are stabilized by these terms, whereas certain other
      wave functions can be destabilized when umklapp processes become strong.

PMID- 23004639
TI  - Tolerance of topological surface states towards magnetic moments: Fe on Bi2Se3.
AB  - We study the effect of Fe impurities deposited on the surface of the topological
      insulator Bi(2)Se(3) by means of core-level and angle-resolved photoelectron
      spectroscopy. The topological surface state reveals surface electron doping when
      the Fe is deposited at room temperature and hole doping with increased linearity
      when deposited at low temperature (~8 K). We show that in both cases the surface
      state remains intact and gapless, in contradiction to current belief. Our results
      suggest that the surface state can very well exist at functional interfaces with
      ferromagnets in future devices.

PMID- 23004640
TI  - In-plane magnetic anisotropy of Fe atoms on Bi2Se3(111).
AB  - The robustness of the gapless topological surface state hosted by a 3D
      topological insulator against perturbations of magnetic origin has been the focus
      of recent investigations. We present a comprehensive study of the magnetic
      properties of Fe impurities on the prototypical 3D topological insulator
      Bi(2)Se(3) using local low-temperature scanning tunneling spectroscopy and
      integral x-ray magnetic circular dichroism techniques. Single Fe adatoms on the
      Bi(2)Se(3) surface, in the coverage range ~ 1% of a monolayer, are heavily
      relaxed into the surface and exhibit a magnetic easy axis within the surface
      plane, contrary to what was assumed in recent investigations on the supposed
      opening of a gap. Using ab initio approaches, we demonstrate that an in-plane
      easy axis arises from the combination of the crystal field and dynamic
      hybridization effects.

PMID- 23004641
TI  - ac Josephson effect in finite-length nanowire junctions with Majorana modes.
AB  - It has been predicted that superconducting junctions made with topological
      nanowires hosting Majorana bound states (MBS) exhibit an anomalous 4pi-periodic
      Josephson effect. Finding an experimental setup with these unconventional
      properties poses, however, a serious challenge: for finite-length wires, the
      equilibrium supercurrents are always 2pi periodic as anticrossings of states with
      the same fermionic parity are possible. We show, however, that the anomaly
      survives in the transient regime of the ac Josephson effect. Transients are,
      moreover, protected against decay by quasiparticle poisoning as a consequence of
      the quantum Zeno effect, which fixes the parity of Majorana qubits. The resulting
      long-lived ac Josephson transients may be effectively used to detect MBS.

PMID- 23004642
TI  - Field-induced p-wave superconducting state of mesoscopic systems.
AB  - By using Bogoliubov-de Gennes equations, we study superconducting (SC) states in
      a quasi-two-dimensional system of radius R. It is shown that no vortices exist in
      s-wave SC samples with R < R(c) ~ xi(0), the T = 0 coherence length. We predict
      that chiral p-wave states exhibit superconductivity for R < R(c) only in the
      presence of a vortex with opposite chirality. This induced SC phase is a
      consequence of nonzero chirality of the pairing order parameter and implies the
      presence of chiral edge currents. Our study may be applied to sharply probing the
      pairing symmetry of unconventional superconductors.

PMID- 23004643
TI  - Superconductor-insulator quantum phase transition in disordered FeSe thin films.
AB  - The evolution of two-dimensional electronic transport with increasing disorder in
      epitaxial FeSe thin films is studied. Disorder is generated by reducing the film
      thickness. The extreme sensitivity of the films to disorder results in a
      superconductor-insulator transition. The finite-size scaling analysis in the
      critical regime based on the Bose-glass model strongly supports the idea of a
      continuous quantum phase transition. The obtained value for the critical-exponent
      product of approximately 7/3 suggests that the transition is governed by quantum
      percolation. Finite-size scaling with the same critical-exponent product is also
      substantiated when the superconductor-insulator transition is tuned with an
      applied magnetic field.

PMID- 23004644
TI  - Quantum-fluctuation effects in the transport properties of ultrathin films of
      disordered superconductors above the paramagnetic limit.
AB  - We study the transport in ultrathin disordered film near the quantum critical
      point induced by the Zeeman field. We calculate corrections to the normal state
      conductivity due to quantum pairing fluctuations. The fluctuation-induced
      transport is mediated by virtual rather than real quasiparticle excitations. We
      find that at zero temperature, where the corrections come from purely quantum
      fluctuations, the Aslamazov-Larkin paraconductivity term, the Maki-Thompson
      interference contribution, and the density of states effects are all of the same
      order. The total correction leads to the negative magnetoresistance. This result
      is in qualitative agreement with the recent transport observations in the
      parallel magnetic field of the homogeneously disordered amorphous films and
      superconducting two-dimensional electron gas realized at the oxide interfaces.

PMID- 23004646
TI  - Quasiparticle dynamics and phonon softening in FeSe superconductors.
AB  - Quasiparticle dynamics of FeSe single crystals revealed by dual-color transient
      reflectivity measurements (DeltaR/R) provides unprecedented information on Fe
      based superconductors. The amplitude of the fast component in DeltaR/R clearly
      gives a competing scenario between spin fluctuations and superconductivity.
      Together with the transport measurements, the relaxation time analysis further
      exhibits anomalous changes at 90 and 230 K. The former manifests a structure
      phase transition as well as the associated phonon softening. The latter suggests
      a previously overlooked phase transition or crossover in FeSe. The electron
      phonon coupling constant lambda is found to be 0.16, identical to the value of
      theoretical calculations. Such a small lambda demonstrates an unconventional
      origin of superconductivity in FeSe.

PMID- 23004645
TI  - Bulk electronic structure of superconducting LaRu2P2 single crystals measured by
      soft-X-ray angle-resolved photoemission spectroscopy.
AB  - We present a soft x-ray angle-resolved photoemission spectroscopy (SX-ARPES)
      study of the stoichiometric pnictide superconductor LaRu(2)P(2). The observed
      electronic structure is in good agreement with density functional theory (DFT)
      calculations. However, it is significantly different from its counterpart in high
      temperature superconducting Fe pnictides. In particular, the bandwidth
      renormalization present in the Fe pnictides (~2-3) is negligible in LaRu(2)P(2)
      even though the mass enhancement is similar in both systems. Our results suggest
      that the superconductivity in LaRu(2) P(2) has a different origin with respect to
      the iron pnictides. Finally, we demonstrate that the increased probing depth of
      SX-ARPES, compared to the widely used ultraviolet ARPES, is essential in
      determining the bulk electronic structure in the experiment.

PMID- 23004647
TI  - Kondo physics in a rare earth ion with well localized 4f electrons.
AB  - Dilute Nd in simple cubic LaB(6) shows electrical resistance and specific heat
      features at low temperature consistent with a Kondo scale of T(K) </~ 0.3 K. Nd
      has a well-localized 4f(3) J = 9/2 Hund's rule configuration which is not
      anticipated to be Kondo coupled to the conduction electrons in LaB(6). We
      conjecture that the unexpected Kondo effect arises via participation of 4f
      quadrupolar degrees of freedom of the Nd crystal-field, ground-state quartet.

PMID- 23004648
TI  - Control of ferromagnetic relaxation in magnetic thin films through thermally
      induced interfacial spin transfer.
AB  - Relaxation control in magnetic thin films via thermally induced interfacial spin
      transfers was demonstrated for the first time. The experiments used a trilayered
      structure that consisted of an yttrium iron garnet (YIG) thin film grown on a
      gadolinium gallium garnet substrate and capped with a nanometer-thick Pt layer.
      As a temperature gradient is applied across the thickness of the structure, there
      exists a spin angular momentum transfer across the YIG/Pt interface. This spin
      transfer results in a torque on YIG magnetic moments. The torque can either speed
      up or slow down the relaxation in the YIG film, depending on the sign of the
      temperature gradient with respect to the trilayered structure.

PMID- 23004649
TI  - Spin-stretching modes in anisotropic magnets: spin-wave excitations in the
      multiferroic Ba2CoGe2O7.
AB  - We studied spin excitations in the magnetically ordered phase of the
      noncentrosymmetric Ba(2)CoGe(2)O(7) in high magnetic fields up to 33 T. In the
      electron spin resonance and far infrared absorption spectra we found several spin
      excitations beyond the two conventional magnon modes expected for such a two
      sublattice antiferromagnet. We show that a multiboson spin-wave theory describes
      these unconventional modes, including spin-stretching modes, characterized by an
      oscillating magnetic dipole and quadrupole moment. The lack of inversion symmetry
      allows each mode to become electric dipole active. We expect that the spin
      stretching modes can be generally observed in inelastic neutron scattering and
      light absorption experiments in a broad class of ordered S > 1/2 spin systems
      with strong single-ion anisotropy and/or noncentrosymmetric lattice structure.

PMID- 23004650
TI  - First order metamagnetic transition in Ho2Ti2O7 observed by vibrating coil
      magnetometry at Milli-Kelvin temperatures.
AB  - We report vibrating coil magnetometry of the spin-ice system Ho(2)Ti(2)O(7) down
      to ~0.04 K for magnetic fields up to 5 T applied parallel to the [111] axis.
      History-dependent behavior emerges below T(0)(*) ~ 0.6 K near zero magnetic
      field, in common with other spin-ice compounds. In large magnetic fields, we
      observe a magnetization plateau followed by a hysteretic metamagnetic transition.
      The temperature dependence of the coercive fields as well as the susceptibility
      calculated from the magnetization identify the metamagnetic transition as a line
      of first order transitions terminating in a critical end point at T(m)(*) 0.37
      ~/= K, B(m) ~/= 1.5 T. The metamagnetic transition in Ho(2)Ti(2)O(7) is strongly
      reminiscent of that observed in Dy(2)Ti(2)O(7), suggestive of a general feature
      of the spin ices.

PMID- 23004651
TI  - Partial disorder in an Ising-spin Kondo lattice model on a triangular lattice.
AB  - A phase diagram of an Ising-spin Kondo lattice model on a triangular lattice near
      1/3 filling is investigated by Monte Carlo simulation. We identify a partially
      disordered phase with the coexistence of magnetic order and paramagnetic moments,
      which was unstable in two-dimensional Ising models with localized spins only. The
      partial disorder emerges in the competing regime between a two-sublattice stripe
      phase and three-sublattice ferrimagnetic phase, at finite temperatures above an
      electronic phase separation. The peculiar magnetic structure accompanies a charge
      order and develops a gap in the electronic structure. The results manifest a
      crucial role of the nonperturbative interplay between spin and charge degrees of
      freedom in stabilizing the partial disorder.

PMID- 23004652
TI  - Laughlin spin-liquid states on lattices obtained from conformal field theory.
AB  - We propose a set of spin system wave functions that is very similar to lattice
      versions of the Laughlin states. The wave functions are conformal blocks of
      conformal field theories and for a filling factor of nu = 1/2 we provide a parent
      Hamiltonian, which is valid for any even number of spins and is at the same time
      a 2D generalization of the Haldane-Shastry model. We also demonstrate that the
      Kalmeyer-Laughlin state is reproduced as a particular case of this model.
      Finally, we discuss various properties of the spin states and point out several
      analogies to known results for the Laughlin states.

PMID- 23004653
TI  - Storage-recovery phenomenon in magnonic crystal.
AB  - The phenomenon of coherent wave trapping and restoration is demonstrated
      experimentally in a magnonic crystal. Unlike the conventional scheme used in
      photonics, the trapping occurs not due to the deceleration of the incident wave
      when it enters the periodic structure but due to excitation of the quasinormal
      modes of the artificial crystal. This excitation occurs at the group velocity
      minima of the decelerated wave in narrow frequency regions near the edges of the
      band gaps of the crystal. The restoration of the traveling wave is implemented by
      means of phase-sensitive parametric amplification of the stored mode.

PMID- 23004654
TI  - Electronic structure changes across the metamagnetic transition in FeRh via hard
      X-ray photoemission.
AB  - Stoichiometric FeRh undergoes a temperature-induced antiferromagnetic (AFM) to
      ferromagnetic (FM) transition at ~350 K. In this Letter, changes in the
      electronic structure accompanying this transition are investigated in epitaxial
      FeRh thin films via bulk-sensitive valence-band and core-level hard x-ray
      photoelectron spectroscopy with a photon energy of 5.95 keV. Clear differences
      between the AFM and FM states are observed across the entire valence-band
      spectrum and these are well reproduced using density-functional theory. Changes
      in the 2p core levels of Fe are also observed and interpreted using Anderson
      impurity model calculations. These results indicate that significant electronic
      structure changes over the entire valence-band region are involved in this AFM-FM
      transition.

PMID- 23004655
TI  - Magnetically driven metal-insulator transition in NaOsO3.
AB  - The metal-insulator transition (MIT) is one of the most dramatic manifestations
      of electron correlations in materials. Various mechanisms producing MITs have
      been extensively considered, including the Mott (electron localization via
      Coulomb repulsion), Anderson (localization via disorder), and Peierls
      (localization via distortion of a periodic one-dimensional lattice) mechanisms.
      One additional route to a MIT proposed by Slater, in which long-range magnetic
      order in a three dimensional system drives the MIT, has received relatively
      little attention. Using neutron and x-ray scattering we show that the MIT in
      NaOsO(3) is coincident with the onset of long-range commensurate three
      dimensional magnetic order. While candidate materials have been suggested, our
      experimental methodology allows the first definitive demonstration of the long
      predicted Slater MIT.

PMID- 23004656
TI  - Ultrafast time-resolved faraday rotation in EuO thin films.
AB  - We have investigated the ultrafast spin dynamics in EuO thin films by time
      resolved Faraday rotation spectroscopy. The photoinduced magnetization is found
      to be increased in a transient manner, accompanied with subsequent
      demagnetization. The dynamical magnetization enhancement showed a maximum
      slightly below the Curie temperature with prolonged tails toward both lower and
      higher temperatures and dominates the demagnetization counterpart at 55 K. The
      magnetization enhancement component decays in ~1 ns. The realization of the
      transient collective ordering is attributable to the enhancement of the f-d
      exchange interaction.

PMID- 23004657
TI  - Finite-temperature properties of Ba(Zr,Ti)O3 relaxors from first principles.
AB  - A first-principles-based technique is developed to investigate the properties of
      Ba(Zr,Ti)O(3) relaxor ferroelectrics as a function of temperature. The use of
      this scheme provides answers to important, unresolved and/or controversial
      questions such as the following. What do the different critical temperatures
      usually found in relaxors correspond to? Do polar nanoregions really exist in
      relaxors? If yes, do they only form inside chemically ordered regions? Is it
      necessary that antiferroelectricity develop in order for the relaxor behavior to
      occur? Are random fields and random strains really the mechanisms responsible for
      relaxor behavior? If not, what are these mechanisms? These ab initio based
      calculations also lead to deep microscopic insight into relaxors.

PMID- 23004658
TI  - Photoisomerization-controlled phase segregation in a submicron confined
      azonematic liquid crystal.
AB  - Deuteron nuclear magnetic resonance is used to study the phase segregation
      behavior of photoisomerizable liquid crystal diheptylazobenzene (7AB) confined
      into cylindrical pores of Anopore membranes. It is demonstrated that the
      concentration of both components in a binary trans-7AB and cis-7AB mixture can be
      controlled dynamically using UV-illumination stimulated trans-to-cis
      photoisomerization and thermally induced cis-to-trans backisomerization. The so
      far elusive temperature-concentration phase diagram of such system is determined
      by comparative analysis of the behavior in bulk, thin-planar, and Anopore
      confining geometry.

PMID- 23004659
TI  - Proposal for manipulating functional interface properties of composite organic
      semiconductors with addition of designed macromolecules.
AB  - The arrangement of the electronic levels in an interface between organic
      semiconductors is crucial for the operation of devices such as solar cells and
      light emitting diodes. With the addition of designed macromolecules, we show that
      it is possible to control the relative position of the highest occupied molecular
      orbital and lowest unoccupied molecular orbital levels, and consequently improve
      the performance. The designed macromolecules consist of two end segments, each
      compatible with one of the interface components, and a central segment which adds
      functionality to the interface. The tails control the position and the
      orientation of the functional units. When the central functional unit is an
      electric dipole, an electrostatic field is created due to the orientation of the
      dipoles, which shifts the electronic levels in a controlled way. We develop a
      theoretical framework, based on self-consistent field theory, to study the
      concentration and the orientation of the central functional units. We find that
      the levels can shift by as much as several tenths of an eV.

PMID- 23004660
TI  - Phenomenological theory of isotropic-genesis nematic elastomers.
AB  - We consider the impact of the elastomer network on the nematic structure and
      fluctuations in isotropic-genesis nematic elastomers, via a phenomenological
      model that underscores the role of network compliance. The model contains a
      network-mediated nonlocal interaction as well as a new kind of random field that
      reflects the memory of the nematic order present at network formation and also
      encodes local anisotropy due to localized nematogenic polymers. This model
      enables us to predict regimes of short-ranged oscillatory spatial correlations
      (thermal and glassy) in the nematic alignment.

PMID- 23004661
TI  - Granular fingering in fluid injection into dense granular media in a Hele-Shaw
      cell.
AB  - We study experimentally spontaneous pattern formation in a dry dense granular
      medium invaded by an aqueous glycerin solution in a radial Hele-Shaw cell. By
      varying the invading fluid viscosity via the weight concentration of glycerin,
      and by adjusting the normalized injection velocity via the injection rate and the
      gap size of the cell, we observe four distinct fluid-grain displacement regimes:
      (i) a simple radial flow regime, (ii) an infiltration-dominated regime, (iii) a
      grain displacement-dominated regime, and (iv) a viscous fingering-dominated
      regime. We argue that these displacement regimes emerge as a result of
      competition among the various energy dissipation mechanisms and can be classified
      based on the characteristic times involved in the injection process.

PMID- 23004662
TI  - Asymmetry and stability of shape kinematics in microswimmers' motion.
AB  - Many swimming microorganisms governed by low Reynolds number hydrodynamics
      utilize flagellar undulations for self-propulsion. Most of the existing
      theoretical models assume that the shape kinematics is directly controlled, while
      in reality, eukaryotes actuate internal bending moments along their flagellum.
      Under this control, the shape is dynamically evolving and periodic gaits may
      become unstable. This Letter addresses the problem by revisiting Purcell's three
      link swimmer model where joint torques are controlled, and the geometric
      symmetries underlying the dynamics of the swimmer are analyzed. It is found that
      one has to break the front-back symmetry of the swimmer's structure and/or
      actuation profile in order to induce stable shape kinematics. The results may
      explain why most of the flagellated eukaryotes swim with their head forward.

PMID- 23004663
TI  - Nonlinearity, fluctuations, and response in sensory systems.
AB  - The statistics of fluctuations in biological sensing pathways and its relation to
      the response to environmental stimuli is investigated. We focus on bacterial
      chemotaxis, where detailed experiments and reliable models are available. We
      consider allosteric models of receptors' activity and derive analytically their
      steady-state probability distribution and correlation times. By using fluctuation
      relations, we then relate appropriate steady-state correlations to the response
      of the system to step and ramp stimuli of arbitrary amplitudes. We show that the
      combined effect of nonlinearity and fluctuations generically yields a complex
      nonlinear response at the single sensing unit and at the whole-cell level. Such
      responses display a nonexponential decay with a broad range of time scales. Slow,
      ineffective responses are associated to signaling units locked into poorly
      performing states. However, the nonlinear response reduces to a nearly
      exponential one for an appropriate range of the kinetic parameters. This provides
      a systematic explanation for the relation between fluctuation and response
      observed in recent experiments.

PMID- 23004664
TI  - Length regulation of active biopolymers by molecular motors.
AB  - For biopolymers like cytoskeletal actin filaments and microtubules, assembly and
      disassembly are inherently dissipative processes. Molecular motors can affect the
      rates of subunit removal at filament ends. We introduce a driven lattice-gas
      model to study the effects of motor-induced depolymerization on the length of
      active biopolymers and find that increasing motor activity sharpens unimodal
      steady-state length distributions. Furthermore, for sufficiently fast moving
      motors, the relative width of the length distribution is determined only by the
      attachment rate of motors. Our results show how established molecular processes
      can be used to robustly regulate the size of cytoskeletal structures like mitotic
      spindles.

PMID- 23004665
TI  - Microtubule length regulation by molecular motors.
AB  - Length regulation of microtubules (MTs) is essential for many cellular processes.
      Molecular motors like kinesin-8, which move along MTs and also act as
      depolymerases, are known as key players in MT dynamics. However, the regulatory
      mechanisms of length control remain elusive. Here, we investigate a stochastic
      model accounting for the interplay between polymerization kinetics and motor
      induced depolymerization. We determine the dependence of MT length and variance
      on rate constants and motor concentration. Moreover, our analyses reveal how
      collective phenomena lead to a well-defined MT length.

PMID- 23004666
TI  - Dynamics of melting and recrystallization in a polymeric micellar crystal
      subjected to large amplitude oscillatory shear flow.
AB  - Shear-induced structural transitions of a micellar cubic phase during large
      amplitude oscillatory shear flow is studied with time-resolved oscillatory
      rheological small angle neutron scattering. This technique allows us to resolve
      the structural changes within a cycle of oscillation. By applying a strain rate
      near the critical melting shear rate, melting and recrystallization occurs in a
      cyclic mode. The maximum degree of order is observed when the shear stress
      reaches a plateau value during the large amplitude oscillatory shear cycle,
      whereas melting is maximized at the strain rate wave peaks. This structural
      evolution confirms the cyclic mechanism of sticking and sliding of 2D hexagonal
      close-packed layers [I. W. Hamley et al., Phys. Rev. E 58, 7620 (1998)].

PMID- 23004667
TI  - Escaping the curse of dimensionality in estimating multivariate transfer entropy.
AB  - Multivariate transfer entropy (TE) is a model-free approach to detect causalities
      in multivariate time series. It is able to distinguish direct from indirect
      causality and common drivers without assuming any underlying model. But despite
      these advantages it has mostly been applied in a bivariate setting as it is hard
      to estimate reliably in high dimensions since its definition involves infinite
      vectors. To overcome this limitation, we propose to embed TE into the framework
      of graphical models and present a formula that decomposes TE into a sum of finite
      dimensional contributions that we call decomposed transfer entropy. Graphical
      models further provide a richer picture because they also yield the causal
      coupling delays. To estimate the graphical model we suggest an iterative
      algorithm, a modified version of the PC-algorithm with a very low estimation
      dimension. We present an appropriate significance test and demonstrate the
      method's performance using examples of nonlinear stochastic delay-differential
      equations and observational climate data (sea level pressure).

PMID- 23004668
TI  - Comment on "First results of the phase II SIMPLE dark matter search".

PMID- 23004670
TI  - Comment on "Stability of the bulk phase of layered ZnO".

PMID- 23004672
TI  - Comment on "Oxygen as a site specific probe of the structure of water and oxide
      materials".

PMID- 23004674
TI  - Comment on "2D atomic mapping of oxidation states in transition metal oxides by
      scanning transmission electron microscopy and electron energy-loss spectroscopy".

PMID- 23004588
TI  - Observation of a new Xib baryon.
AB  - The observation of a new b baryon via its strong decay into Xi(b)(-) pi(+) (plus
      charge conjugates) is reported. The measurement uses a data sample of pp
      collisions at sqrt[s] = 7 TeV collected by the CMS experiment at the LHC,
      corresponding to an integrated luminosity of 5.3 fb(-1). The known Xi(b)(-)
      baryon is reconstructed via the decay chain Xi(b)(-) -> J/psiXi(-) -> MU(+) MU(-)
      Lambda(0) pi(-), with Lambda(0) -> ppi(-). A peak is observed in the distribution
      of the difference between the mass of the Xi(b)(-) pi(+) system and the sum of
      the masses of the Xi(b)(-) and pi(+), with a significance exceeding 5 standard
      deviations. The mass difference of the peak is 14.84 +/- 0.74(stat) +/-
      0.28(syst) MeV. The new state most likely corresponds to the J(P) = 3/2(+)
      companion of the Xi(b).

PMID- 23004676
TI  - Laparoscopic-assisted versus open surgery for colorectal cancer: short- and long
      term outcomes comparison.
AB  - BACKGROUND: Despite the theoretical advantages of laparoscopic surgery, it is
      still not considered the standard treatment for colorectal cancer patients
      because of criticism concerning oncologic stability. This study aimed at
      examining the short- and long-term follow-up results of laparoscopic surgery
      versus open surgery for colorectal cancer and at investigating clinical outcomes,
      oncologic safety, and any potential advantages of laparoscopic colorectal cancer
      resection. SUBJECTS AND METHODS: We retrospectively analyzed a database
      containing the information about patients who underwent surgery for stage I-III
      colorectal cancer from January 2004 to January 2012 at our institution. RESULTS:
      The patients who underwent the laparoscopic-assisted procedure showed a
      significantly faster recovery than those who underwent open surgery, namely, less
      time to first passing flatus (P=.041), time of first bowel motion (P=.04), time
      to resume normal diet (P=.043), and time to walk independently (P=.031).
      Laparoscopic colorectal surgery caused less pain for patients, leading to lower
      need of analgesic (P=.002) and less hospital recovery time (P=.034), compared
      with patients who underwent open surgery. No differences were found in 3- and 5
      year overall and disease-free survival rates. CONCLUSIONS: Our results suggested
      that the laparoscopic approach was as safe as the open alternative. Laparoscopic
      assisted surgery has been shown to be a favorable surgical option with better
      short-term outcomes and similar long-term oncological control compared with open
      resection.

PMID- 23004679
TI  - Loss of caveolin-1 from bronchial epithelial cells and monocytes in human
      subjects with asthma.
AB  - BACKGROUND: Caveolin-1 has emerged as a critical regulator of signaling pathways
      involved in lung fibrosis and inflammation. METHODS: Therefore, we investigated
      whether caveolin-1 is deficient in asthmatic patients and in a murine model of
      asthma. RESULTS: Immunohistochemical analyses of endobronchial biopsies showed a
      remarkable loss of caveolin-1 in the lungs of asthmatic patients compared with
      controls. This loss was most evident in bronchial epithelial cells and associated
      with an increase in the expression of extracellular matrix proteins: collagen I,
      tenascin, and periostin. Cultured primary bronchial epithelial cells of
      asthmatics had lower caveolin-1 expression compared with control cells. In
      addition, caveolin-1 expression was significantly decreased in peripheral blood
      monocytes from asthma patients. The loss of caveolin-1 was also observed in a
      mouse model for asthma (mice sensitized and challenged with aspergillus
      fumigatus). CONCLUSIONS: To our knowledge, this is the first demonstration that
      the regulatory protein caveolin-1 is reduced in patients with asthma.

PMID- 23004681
TI  - Treatment of primary follicular mucinosis with imiquimod 5% cream.
AB  - Follicular mucinosis can develop as a primary form or associated with other
      benign or malignant skin conditions. We present a case of primary follicular
      mucinosis in which complete clinical remission was achieved after treatment with
      topical imiquimod 5%. Primary follicular mucinosis (PFM), also called idiopathic
      alopecia mucinosa, is considered a distinct entity, the clinical course of which
      is usually benign, but its pathogenesis remains unclear. There is no standard
      treatment for PFM, and a wide variety of therapies have been described. There are
      no previous reports of treatment of PFM with imiquimod. 

PMID- 23004678
TI  - Comparative proteomic study for profiling differentially expressed proteins
      between Chinese left- and right-sided colon cancers.
AB  - The aim of the present study is to profile differentially expressed protein
      markers between left-sided colon cancer (LSCC) and right-sided colon cancer
      (RSCC). Fresh tumor tissue samples from LSCC (n = 7) and RSCC (n = 7) groups were
      analyzed by two-dimensional electrophoresis coupled with MALDI-TOF-MS, followed
      by Western blotting. In 50 paraffin embedded samples from each group, levels of
      four differentially expressed proteins (identified by proteomics analysis) were
      measured by tissue microarray with immunohistochemistry staining to compare the
      different protein markers between LSCC and RSCC. Sixteen proteins were found to
      be differentially expressed between LSCC and RSCC. Ten proteins including HSP-60
      and PDIA1 were identified to be highly expressed in LSCC (P < 0.01 or P < 0.05),
      while the expression of six proteins including EEF1D and HSP-27 were higher in
      RSCC (P < 0.01 or P < 0.05). Virtually all of the indentified proteins were
      involved in cellular energy metabolism, protein folding/unfolding, and/or
      oxidative stress. Human colon tumors at various locations have different
      proteomic biomarkers. Differentially expressed proteins associated with energy
      metabolism, protein folding/unfolding and oxidative stress contribute to
      different tumorigenesis, tumor progression, and prognosis between left- and right
      sided colon cancer.

PMID- 23004680
TI  - Arthritis as an important determinant for psoriatic patients to develop severe
      vascular events in Taiwan: a nation-wide study.
AB  - BACKGROUND: Psoriasis is an important systemic inflammatory disease that often
      leads to severe vascular diseases. This study was launched to determine if joint
      involvement affects incidence of vascular comorbidities in psoriatic patients. In
      addition, potential vasculo-protective effects of methotrexate in psoriatic
      patients were also evaluated. METHOD: A population-based retrospective cohort
      study was conducted using the Taiwanese National Health Insurance database
      spanning from 1996 to 2006. Accordingly, 7648 and 284 psoriatic patients without
      or with arthritis, respectively, were identified. To ensure the temporal
      relationship between different events, those with date of first diagnosis
      psoriasis during the year of 1996 were excluded from subsequent analyses. In
      addition, those with diagnosis of cerebrovascular or cardiovascular diseases
      prior to onset of psoriasis were also excluded from relevant subsequent analyses.
      RESULT: Taking psoriatic patients without arthritis as the referent group, the
      hazard ratio for incident cerebrovascular disease was 1.82 (95% CI = 1.17-2.82)
      for psoriatic patient with arthritis. In addition, psoriatic patients without
      arthritis who had methotrexate treatment showed reduced risks for incident
      cerebrovascular disease as compared with those with no arthritis and had received
      no methotrexate/retinoid treatment. Similar analyses were performed on
      cardiovascular diseases, and equivalent results were obtained. CONCLUSION: Our
      study indicated that arthritis is a potential determinant for psoriatic patients
      in terms of incident vascular comorbidities. In addition, methotrexate treatment
      may be associated with reduced risks for development of severe vascular diseases
      in psoriatic patients without arthritis. Further studies should focus on the
      clinical complications associated with psoriatic patients with or without
      arthritis.

PMID- 23004682
TI  - Ranking of dental and somatic pain sensations among paediatric dental patients.
AB  - BACKGROUND: Children suffer from somatic and dental pain, which may interfere
      with their everyday life. Pain self-report tools are available for children.
      Research is needed to better understand the perception of dental pain in
      comparison with pain in other organs. AIM: To investigate relations between the
      perceptions of dental and somatic pain complaints among school-age children.
      DESIGN: One hundred and two children, aged 7-17 years (mean age, 11.5 +/- 2.65
      years), completed questioners regarding their somatic and dental: 1. Memory pain
      rank (MPR) and 2. Wong-Baker FACES Pain Rating Scale (FRS). RESULTS: Children
      reported increased dental pain after school in both scales (P = 0.015 in MPR). In
      both MPR and FRS, the pattern of pain ranking was similar: Abdominal pain was
      scored highest (2.75 +/- 1.4 and 1.56 +/- 1.63, respectively), followed by
      headache, ear, dental and TMJ (Temporomandibular joint). CONCLUSION: There was a
      strong correlation between pain perception and current pain scores in every
      organ. Somatic pain, namely head, abdomen and ears, was ranked significantly
      higher than dental and TMJ pain. School-aged children rank current pain and pain
      experience significantly lower while they are pre-occupied (school time) in
      comparison with times when they are less busy (after school time).

PMID- 23004677
TI  - Protective effect of nectandrin B, a potent AMPK activator on neointima
      formation: inhibition of Pin1 expression through AMPK activation.
AB  - BACKGROUND AND PURPOSE: Neointima is considered a critical event in the
      development of vascular occlusive disease. Nectandrin B from nutmeg functions as
      a potent AMP-activated protein kinase (AMPK) activators. The present study
      addressed whether nectandrin B inhibits intimal hyperplasia in guide wire-injured
      arteries and examined its molecular mechanism. EXPERIMENTAL APPROACH: Neointima
      was induced by guide wire injury in mouse femoral arteries. Cell proliferation
      and mechanism studies were performed in rat vascular smooth muscle cells (VSMC)
      culture model. KEY RESULTS: Nectandrin B increased AMPK activity in VSMC.
      Nectandrin B inhibited the cell proliferation induced by PDGF and DNA synthesis.
      Moreover, treatment of nectandrin B suppressed neointima formation in femoral
      artery after guide wire injury. We have recently shown that Pin1 plays a critical
      role in VSMC proliferation and neointima formation. Nectandrin B potently blocked
      PDGF-induced Pin1 and cyclin D1 expression and nectandrin B's anti-proliferation
      effect was diminished in Pin1 overexpressed VSMC. PDGF-induced phosphorylation of
      ERK and Akt was marginally affected by nectandrin B. However, nectandrin B
      increased the levels of p53 and its downstream target p21 and, also reversibly
      decreased the expression of E2F1 and phosphorylated Rb in PDGF-treated VSMC. AMPK
      inhibition by dominant mutant form of adenovirus rescued nectandrin B-mediated
      down-regulation of Pin1 and E2F1. CONCLUSIONS AND IMPLICATIONS: Nectandrin B
      inhibited VSMC proliferation and neointima formation via inhibition of E2F1
      dependent Pin1 gene transcription, which is mediated through the activation of an
      AMPK/p53-triggered pathway.

PMID- 23004683
TI  - Gold nanoparticles as electronic bridges for laccase-based biocathodes.
AB  - Direct electron transfer (DET) reactions between redox enzymes and electrodes can
      be maximized by oriented immobilization of the enzyme molecules onto an
      electroactive surface modified with functionalized gold nanoparticles (AuNPs).
      Here, we present such strategy for obtaining a DET-based laccase (Lc) cathode for
      O(2) electroreduction at low overpotentials. The stable nanostructured enzymatic
      electrode is based on the step-by-step covalent attachment of AuNPs and Lc
      molecules to porous graphite electrodes using the diazonium salt reduction
      strategy. Oriented immobilization of the enzyme molecules on adequately
      functionalized AuNPs allows establishing very fast DET with the electrode via
      their Cu T1 site. The measured electrocatalytic waves of O(2) reduction can be
      deconvoluted into two contributions. The one at lower overpotentials corresponds
      to immobilized Lc molecules that are efficiently wired by the AuNPs with a
      heterogeneous electron transfer rate constant k(0) ? 400 s(-1).

PMID- 23004684
TI  - Reduction of lipid-laden macrophage index after laparoscopic Nissen
      fundoplication in cystic fibrosis patients after lung transplantation.
AB  - BACKGROUND: Lipid-laden macrophage (LLM) index could be potentially useful in
      assessing gastroesophageal (GE) reflux and aspiration after lung transplantation
      (LT) in patients with cystic fibrosis (CF). METHODS: A retrospective review of CF
      patients undergoing LT and/or laparoscopic Nissen fundoplication (LNF) from
      January 1, 2009, to December 31, 2011, was performed. RESULTS: Seventeen CF
      patients (nine women), mean (+/- SD) age 27.9 +/- 7.5 yr, underwent LT with mean
      (+/- SD) pre-transplant FEV(1) of 20.9 +/- 5.0% predicted. Seventy percentage
      (12/17) of patients underwent LNF without complications within 1-2 wk of LT.
      After LT, but prior to antireflux surgery, there was no significant difference in
      the mean (+/- SD) baseline LLM index (154 +/- 41 vs. 146 +/- 51, p = NS) between
      patients who were to undergo LNF and patients who did not. After LNF, a
      significant reduction in the mean (+/- SD) LLM index occurred following the
      procedure (154 +/- 41-74 +/- 54, p < 0.0001) while each patient reported
      resolution of symptoms of GE reflux, whereas 40% (2/5) undergoing only medical
      treatment reported resolution of symptoms. CONCLUSIONS: Significant reduction in
      the LLM index occurred after LNF in CF patients after LT that correlated with
      resolution of clinical symptoms of GE reflux.

PMID- 23004685
TI  - Novel West Nile virus lineage 1a full genome sequences from human cases of
      infection in north-eastern Italy, 2011.
AB  - During 2008-2009, several human cases of WNV disease caused by an endemic lineage
      1a strain were reported in areas surrounding the Po river in north-eastern Italy.
      Since 2010, cases have been recorded in nearby northern areas, where, in 2011,
      both lineage 1a and 2 were detected. We describe here two new WNV complete genome
      sequences from human cases of WNV infection occurring in 2011 in the Veneto
      Region. Phylogenetic analysis showed that both genome sequences belonged to
      lineage 1a and were related to WNV strains of the Western Mediterranean subtype.
      The novel WNV genomes had high nucleotide and amino acid sequence divergence from
      each other and from the WNV strain circulating in Italy in 2008-2009. The
      presence of different WNV strains in a relatively small geographical area is a
      novel finding with unpredictable impact on human disease that requires further
      investigation.

PMID- 23004686
TI  - The predictive validity of the RSI QuickScan questionnaire with respect to arm,
      shoulder and neck symptoms in computer workers.
AB  - The aim of this study was to determine whether results from the RSI QuickScan
      questionnaire on risk factors for arm, shoulder and neck symptoms can predict
      future arm, neck and shoulder symptoms in a population of computer workers. For
      this prospective cohort study, with a follow-up of 24 months, 3383 workers who
      regularly worked with a computer were approached. Generalised estimating
      equations (GEE) with 6, 12, 18 and 24 months time lags were used to determine
      whether high exposure was related to symptoms at follow-up. The results showed
      that high scores on 9 out of 13 scales, including previous symptoms, were
      significantly related to arm, shoulder and neck symptoms at follow-up. These
      results provide support for the predictive validity of the RSI QuickScan
      questionnaire. PRACTITIONER SUMMARY: The results showed that high scores on 9 out
      of 13 scales, including previous symptoms, were significantly related to arm,
      shoulder and neck symptoms at follow-up. The RSI QuickScan questionnaire may be
      recommended as a tool in the identification of computer workers who should be
      targeted with interventions aimed at prevention of future symptoms.

PMID- 23004688
TI  - Geometric microcanonical thermodynamics for systems with first integrals.
AB  - In the general case of a many-body Hamiltonian system described by an autonomous
      Hamiltonian H and with K >= 0 independent conserved quantities, we derive the
      microcanonical thermodynamics. Using simple approach, based on differential
      geometry, we derive the microcanonical entropy and the derivatives of the entropy
      with respect to the conserved quantities. In such a way, we show that all the
      thermodynamical quantities, such as the temperature, the chemical potential, and
      the specific heat, are measured as a microcanonical average of the appropriate
      microscopic dynamical functions that we have explicitly derived. Our method
      applies also in the case of nonseparable Hamiltonians, where the usual definition
      of kinetic temperature, derived by the virial theorem, does not apply.

PMID- 23004687
TI  - Microfluidic device for the selective chemical stimulation of neurons and
      characterization of peptide release with mass spectrometry.
AB  - Neuropeptides are synthesized in and released from neurons and are involved in a
      wide range of physiological processes, including temperature homeostasis,
      learning, memory, and disease. When working with sparse neuronal networks, the
      ability to collect and characterize small sample volumes is important as neurons
      often release only a small proportion of their mass-limited content. Microfluidic
      systems are well suited for the study of neuropeptides. They offer the ability to
      control and manipulate the extracellular environment and small sample volumes,
      thereby reducing the dilution of peptides following release. We present an
      approach for the culture and stimulation of a neuronal network within a
      microfluidic device, subsequent collection of the released peptides, and their
      detection via mass spectrometry. The system employs microvalve-controlled
      stimulation channels to selectively stimulate a low-density neuronal culture,
      allowing us to determine the temporal onset of peptide release. Released peptides
      from the well-characterized, peptidergic bag cell neurons of Aplysia californica
      were collected and their temporal pattern of release was characterized with
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We
      show a robust difference in the timing of release for chemical solutions
      containing elevated K(+) (7 +/- 3 min), when compared to insulin (19 +/- 7 min)
      (p < 0.000 01).

PMID- 23004689
TI  - Quantum quenches in disordered systems: approach to thermal equilibrium without a
      typical relaxation time.
AB  - We study spectral properties and the dynamics after a quench of one-dimensional
      spinless fermions with short-range interactions and long-range random hopping. We
      show that a sufficiently fast decay of the hopping term promotes localization
      effects at finite temperature, which prevents thermalization even if the
      classical motion is chaotic. For slower decays, we find that thermalization does
      occur. However, within this model, the latter regime falls in an unexpected
      universality class, namely, observables exhibit a power-law (as opposed to an
      exponential) approach to their thermal expectation values.

PMID- 23004690
TI  - Upper critical dimension of the Kardar-Parisi-Zhang equation.
AB  - Numerical results for the directed polymer model in 1+4 dimensions in various
      types of disorder are presented. The results are obtained for a system size that
      is considerably larger than considered previously. For the extreme "strong"
      disorder case (min-max system), associated with the directed percolation model,
      the expected value of the meandering exponent, zeta=0.5, is clearly revealed,
      with very weak finite size effects. For the "weak disorder" case, associated with
      the Kardar-Parisi-Zhang equation, finite size effects are stronger, but the value
      of zeta is clearly seen in the vicinity of 0.57. In systems with strong disorder
      it is expected that the system will cross over sharply from min-max behavior at
      short chains to weak disorder behavior at long chains. Our numerical results
      agree with that expectation. To complete the picture we obtain the energy
      fluctuation exponent omega for weak disorder, and we find that the value of omega
      is in the vicinity of 0.14. Thus, the meandering exponent and the energy
      fluctuation exponent obey the strong coupling scaling relation 2xi-omega=1. Our
      results indicate that 1+4 is not the upper critical dimension in the weak
      disorder case, and thus 4+1 does not seem to be the upper critical dimension for
      the Kardar-Parisi-Zhang equation.

PMID- 23004691
TI  - Normal and anomalous diffusion in random potential landscapes.
AB  - A relation between the effective diffusion coefficient in a lattice with random
      site energies and random transition rates and the macroscopic conductivity in a
      random resistor network allows for elucidating possible sources of anomalous
      diffusion in random potential models. We show that subdiffusion is only possible
      either if the mean Boltzmann factor in the corresponding potential diverges or if
      the percolation concentration in the system is equal to unity (or both), and that
      superdiffusion is impossible in our system under any condition. We show also
      other useful applications of this relation.

PMID- 23004692
TI  - Validity of projected Gross-Pitaevskii simulation: comparison with quantum Monte
      Carlo.
AB  - We examine the validity of the projected Gross-Pitaevskii simulation by taking
      the two-dimensional homogeneous bosonic system as an example. The long-distance
      behaviors of the correlation function and equilibrium temperatures show good
      agreement with those of the quantum Monte Carlo calculations below temperatures
      near the Kosterlitz-Thouless transition. We find that in the projected Gross
      Pitaevskii description, one needs to estimate the optimal wave-number cutoff in
      temperature. In the well-described region, the projected Gross-Pitaevskii
      equation presents reliable predictions for the long-wave bosonic components.

PMID- 23004693
TI  - Nonlinear elastic model for faceting of vesicles with soft grain boundaries.
AB  - We use an elastic model to explore faceting of solid-wall vesicles with elastic
      heterogeneities. We show that faceting occurs in regions where the vesicle wall
      is softer, such as areas of reduced wall thicknesses or concentrated in
      crystalline defects. The elastic heterogeneities are modeled as a second
      component with reduced elastic parameters. Using simulated annealing Monte Carlo
      simulations we obtain the vesicle shape by optimizing the distributions of facets
      and boundaries. Our model allows us to reduce the effects of the residual stress
      generated by crystalline defects, and reveals a robust faceting mechanism into
      polyhedra other than the icosahedron.

PMID- 23004694
TI  - Dimensional crossover in fluids under nanometer-scale confinement.
AB  - Several earlier studies have shown signatures of crossover in various static and
      dynamics properties of a confined fluid when the confining dimension decreases to
      about a nanometer. The density fluctuations govern the majority of such
      properties of a fluid. Here, we illustrate the crossover in density fluctuation
      in a confined fluid, to provide a generic understanding of confinement-induced
      crossover of fluid properties, using computer simulations. The crossover can be
      understood as a manifestation of changes in the long-wavelength behavior of
      fluctuation in density due to geometrical constraints. We further show that the
      confining potential significantly affects the crossover behavior.

PMID- 23004695
TI  - Nucleation and growth of droplets in vapor-liquid transitions.
AB  - Results for the kinetics of vapor-liquid transitions, following temperature
      quenches with different densities, are presented from molecular dynamics
      simulations of a Lennard-Jones system. For a critical density, bicontinuous
      liquid and vapor domains are observed which grow with time, obeying the
      predictions for the hydrodynamic mechanism. On the other hand, for quenches with
      density significantly below the critical one, phase separation progresses via
      nucleation and growth of liquid droplets. In the latter case, the Brownian
      diffusion and collision mechanism for the droplet growth is confirmed. We also
      discuss the possibility of interdroplet interaction leading to a different
      amplitude in the growth law. Arguments for faster growth, observed at early
      times, are also provided.

PMID- 23004696
TI  - Conformal smectics and their many metrics.
AB  - We establish that equally spaced smectic configurations enjoy an infinite
      dimensional conformal symmetry and show that there is a natural map between them
      and null hypersurfaces in maximally symmetric spacetimes. By choosing the
      appropriate conformal factor it is possible to restore additional symmetries of
      focal structures only found before for smectics on flat substrates.

PMID- 23004697
TI  - Persistence of a Brownian particle in a time-dependent potential.
AB  - We investigate the persistence probability of a Brownian particle in a harmonic
      potential, which decays to zero at long times, leading to an unbounded motion of
      the Brownian particle. We consider two functional forms for the decay of the
      confinement, an exponential decay and an algebraic decay. Analytical calculations
      and numerical simulations show that for the case of the exponential relaxation,
      the dynamics of Brownian particle at short and long times are independent of the
      parameters of the relaxation. On the contrary, for the algebraic decay of the
      confinement, the dynamics at long times is determined by the exponent of the
      decay. Finally, using the two-time correlation function for the position of the
      Brownian particle, we construct the persistence probability for the Brownian
      walker in such a scenario.

PMID- 23004698
TI  - Escape rate for a quantum particle moving in a time-periodic rapidly oscillating
      potential: a time-independent approach.
AB  - We explore, in the quantum regime, the stochastic dynamics of a time-periodic,
      rapidly oscillating potential (having a characteristic frequency of omega) within
      the framework of a time-dependent system-reservoir Hamiltonian. We invoke the
      idea of a quantum gauge transformation in light of the standard Floquet theorem
      in an attempt to construct a Langevin equation (bearing a time-independent
      effective potential) by employing a systematic perturbative expansion in powers
      of omega^{-1} using the natural time-scale separation. The time-independent
      effective potential (corrected to omega^{-2} in leading order) that acts on the
      slow motion of the driven particle can be employed for trapping. We proceed
      further to evaluate the rate of escape of the driven particle from the metastable
      state in the high-temperature limit. We also envisage a resonance phenomena, a
      true hallmark of the system-reservoir quantization. This development would thus
      serve as a model template to investigate the trapping mechanism, as well as an
      appropriate analog to understand the dynamics of a fluctuation-induced escape
      process from the trap.

PMID- 23004699
TI  - Correlated continuous-time random walks in external force fields.
AB  - We study the anomalous diffusion of a particle in an external force field whose
      motion is governed by nonrenewal continuous time random walks with correlated
      waiting times. In this model the current waiting time T_{i} is equal to the
      previous waiting time T_{i-1} plus a small increment. Based on the associated
      coupled Langevin equations the force field is systematically introduced. We show
      that in a confining potential the relaxation dynamics follows power-law or
      stretched exponential pattern, depending on the model parameters. The process
      obeys a generalized Einstein-Stokes-Smoluchowski relation and observes the second
      Einstein relation. The stationary solution is of Boltzmann-Gibbs form. The case
      of an harmonic potential is discussed in some detail. We also show that the
      process exhibits aging and ergodicity breaking.

PMID- 23004700
TI  - Avalanche frontiers in the dissipative Abelian sandpile model and off-critical
      Schramm-Loewner evolution.
AB  - Avalanche frontiers in Abelian sandpile model (ASM) are random simple curves
      whose continuum limit is known to be a Schramm-Loewner evolution with diffusivity
      parameter kappa=2. In this paper we consider the dissipative ASM and study the
      statistics of the avalanche and wave frontiers for various rates of dissipation.
      We examine the scaling behavior of a number of functions, such as the correlation
      length, the exponent of distribution function of loop lengths, and the gyration
      radius defined for waves and avalanches. We find that they do scale with the rate
      of dissipation. Two significant length scales are observed. For length scales
      much smaller than the correlation length, these curves show properties close to
      the critical curves, and the corresponding diffusivity parameter is nearly the
      same as the critical limit. We interpret this as the ultraviolet limit where
      kappa=2 corresponding to c=-2. For length scales much larger than the correlation
      length, we find that the avalanche frontiers tend to self-avoiding walk, and the
      corresponding driving function is proportional to the Brownian motion with the
      diffusivity parameter kappa=8/3 corresponding to a field theory with c=0. We
      interpret this to be the infrared limit of the theory or at least a crossover.

PMID- 23004701
TI  - Kinetic equations governing Smoluchowski dynamics in equilibrium.
AB  - We continue our study of the statistical properties of particles in equilibrium
      obeying Smoluchowski dynamics. We show that the system is governed by a kinetic
      equation of the memory function form and that the memory function is given by one
      of the self-energies available via perturbation theory as introduced in previous
      work. We determine the memory function explicitly to second order in an expansion
      in a pseudopotential. The method we use allows for a straightforward computation
      of corrections via a formal expansion and we therefore view it as an improvement
      over the conventional mode-coupling theory (MCT) formalism where it is not clear
      how to make systematic corrections. In addition, the formalism we have introduced
      is flexible enough to allow for a wide array of different approximation schemes,
      including density expansions. The convergence criteria for our formal series are
      not worked out here, but the second-order equation that we derive is promising in
      the sense that it leads to analytic and numerical results consistent with
      expectations from computer simulations of the hard-sphere system in addition to
      replicating the desired features from conventional MCT (e.g., a two-step decay).
      These particular solutions will be discussed in forthcoming work.

PMID- 23004702
TI  - Flaw strength distributions and statistical parameters for ceramic fibers: the
      normal distribution.
AB  - The present paper investigates large sets of ceramic fibre failure strengths (500
      to 1000 data) produced using tensile tests on tows that contained either 500 or
      1000 filaments. The probability density function was determined through acoustic
      emission monitoring which allowed detection and counting of filament fractures.
      The statistical distribution of filament strengths was described using the normal
      distribution. The Weibull equation was then fitted to this normal distribution
      for estimation of statistical parameters. A perfect agreement between both
      distributions was obtained, and a quite negligible scatter in statistical
      parameters was observed, as opposed to the wide variability that is reported in
      the literature. Thus it was concluded that flaw strengths are distributed
      normally and that the statistical parameters that were derived are the true ones.
      In a second step, the conventional method of estimation of Weibull parameters was
      applied to these sets of data and, then, to subsets selected randomly. The
      influence of other factors involved in the conventional method of determination
      of statistical parameters is discussed. It is demonstrated that selection of
      specimens, sample size, and method of construction of so-called Weibull plots are
      responsible for statistical parameters variability.

PMID- 23004703
TI  - Work fluctuations for Bose particles in grand canonical initial states.
AB  - We consider bosons in a harmonic trap and investigate the fluctuations of the
      work performed by an adiabatic change of the trap curvature. Depending on the
      reservoir conditions such as temperature and chemical potential that provide the
      initial equilibrium state, the exponentiated work average (EWA) defined in the
      context of the Crooks relation and the Jarzynski equality may diverge if the trap
      becomes wider. We investigate how the probability distribution function (PDF) of
      the work signals this divergence. It is shown that at low temperatures the PDF is
      highly asymmetric with a steep fall-off at one side and an exponential tail at
      the other side. For high temperatures it is closer to a symmetric distribution
      approaching a Gaussian form. These properties of the work PDF are discussed in
      relation to the convergence of the EWA and to the existence of the hypothetical
      equilibrium state to which those thermodynamic potential changes refer that enter
      both the Crooks relation and the Jarzynski equality.

PMID- 23004704
TI  - Phase transition in the Jarzynski estimator of free energy differences.
AB  - The transition between a regime in which thermodynamic relations apply only to
      ensembles of small systems coupled to a large environment and a regime in which
      they can be used to characterize individual macroscopic systems is analyzed in
      terms of the change in behavior of the Jarzynski estimator of equilibrium free
      energy differences from nonequilibrium work measurements. Given a fixed number of
      measurements, the Jarzynski estimator is unbiased for sufficiently small systems.
      In these systems the directionality of time is poorly defined and the
      configurations that dominate the empirical average, but which are in fact typical
      of the reverse process, are sufficiently well sampled. As the system size
      increases the arrow of time becomes better defined. The dominant atypical
      fluctuations become rare and eventually cannot be sampled with the limited
      resources that are available. Asymptotically, only typical work values are
      measured. The Jarzynski estimator becomes maximally biased and approaches the
      exponential of minus the average work, which is the result that is expected from
      standard macroscopic thermodynamics. In the proper scaling limit, this regime
      change has been recently described in terms of a phase transition in variants of
      the random energy model. In this paper this correspondence is further
      demonstrated in two examples of physical interest: the sudden compression of an
      ideal gas and adiabatic quasistatic volume changes in a dilute real gas.

PMID- 23004705
TI  - Conditional pair distributions in many-body systems: exact results for Poisson
      ensembles.
AB  - We introduce a conditional pair distribution function (CPDF) which characterizes
      the probability density of finding an object (e.g., a particle in a fluid) to
      within a certain distance of each other, with each of these two having a nearest
      neighbor to a fixed but otherwise arbitrary distance. This function describes
      special four-body configurations, but also contains contributions due to the so
      called mutual nearest neighbor (two-body) and shared neighbor (three-body)
      configurations. The CPDF is introduced to improve a Helmholtz free energy method
      based on space partitions. We derive exact expressions of the CPDF and various
      associated quantities for randomly distributed, noninteracting points at
      Euclidean spaces of one, two, and three dimensions. Results may be of interest in
      many diverse scientific fields, from fluid physics to social and biological
      sciences.

PMID- 23004706
TI  - Directed transport of confined Brownian particles with torque.
AB  - We investigate the influence of an additional torque on the motion of Brownian
      particles confined in a channel geometry with varying width. The particles are
      driven by random fluctuations modeled by an Ornstein-Uhlenbeck process with given
      correlation time tau_{c}. The latter causes persistent motion and is implemented
      as (i) thermal noise in equilibrium and (ii) noisy propulsion in nonequilibrium.
      In the nonthermal process a directed transport emerges; its properties are
      studied in detail with respect to the correlation time, the torque, and the
      channel geometry. Eventually, the transport mechanism is traced back to a
      persistent sliding of particles along the even boundaries in contrast to
      scattered motion at uneven or rough ones.

PMID- 23004707
TI  - Interfacial territory covered by surface-mediated diffusion.
AB  - We consider a minimal model of heterogeneous catalysis in which a molecule
      performs surface-mediated diffusion inside a confining domain whose boundary
      contains catalytic sites. We explicitly take into account the combination of
      surface and bulk diffusion, and we obtain exact results for the mean and variance
      of the territory covered on the boundary by the particle before its exit in the
      case of a two-dimensional spherical domain. Depending on the relative positions
      of the entrance and exit points, very different behaviors with respect to the
      mean adsorption time of the molecule on the surface are found. We also determine
      both exact lower and upper bounds and an approximate expression of the
      probability of reacting with catalytic sites before exiting the domain. These
      results provide a quantitative measure of the efficiency of an idealized
      catalyst.

PMID- 23004708
TI  - Quantum annealing with antiferromagnetic fluctuations.
AB  - We introduce antiferromagnetic quantum fluctuations into quantum annealing in
      addition to the conventional transverse-field term. We apply this method to the
      infinite-range ferromagnetic p-spin model, for which the conventional quantum
      annealing has been shown to have difficulties in finding the ground state
      efficiently due to a first-order transition. We study the phase diagram of this
      system both analytically and numerically. Using the static approximation, we find
      that there exists a quantum path to reach the final ground state from the trivial
      initial state that avoids first-order transitions for intermediate values of p.
      We also study numerically the energy gap between the ground state and the first
      excited state and find evidence for intermediate values of p for which the time
      complexity scales polynomially with the system size at a second-order transition
      point along the quantum path that avoids first-order transitions. These results
      suggest that quantum annealing would be able to solve this problem with
      intermediate values of p efficiently, in contrast to the case with only simple
      transverse-field fluctuations.

PMID- 23004709
TI  - Entropy production in full phase space for continuous stochastic dynamics.
AB  - Total entropy production and its three constituent components are described both
      as fluctuating trajectory-dependent quantities and as averaged contributions in
      the context of the continuous Markovian dynamics, described by stochastic
      differential equations with multiplicative noise, of systems with both odd and
      even coordinates with respect to time reversal, such as dynamics in full phase
      space. Two of these constituent quantities obey integral fluctuation theorems and
      are thus rigorously positive in the mean due to Jensen's inequality. The third,
      however, is not and furthermore cannot be uniquely associated with
      irreversibility arising from relaxation, nor with the breakage of detailed
      balance brought about by nonequilibrium constraints. The properties of the
      various contributions to total entropy production are explored through the
      consideration of two examples: steady-state heat conduction due to a temperature
      gradient, and transitions between stationary states of drift diffusion on a ring,
      both in the context of the full phase space dynamics of a single Brownian
      particle.

PMID- 23004710
TI  - Short time cycles of purely quantum refrigerators.
AB  - Four stroke Otto refrigerator cycles with no classical analog are studied.
      Extremely short cycle times with respect to the internal timescale of the working
      medium characterize these refrigerators. Therefore, these cycles are termed
      sudden. The sudden cycles are characterized by the stable limit cycle, which is
      the invariant of the global cycle propagator. During their operation the states
      of the working medium possess significant coherence which is not erased in the
      equilibration segments due to the very short time allocated. This characteristic
      is reflected in a difference between the energy entropy and the Von Neumann
      entropy of the working medium. A classification scheme for sudden refrigerators
      is developed allowing simple approximations for the cooling power and coefficient
      of performance.

PMID- 23004711
TI  - Work relation and the second law of thermodynamics in nonequilibrium steady
      states.
AB  - We extend Jarzynski's work relation and the second law of thermodynamics to a
      heat conducting system, which is operated by an external agent. These extensions
      contain a nonequilibrium contribution expressed as the violation of the (linear)
      response relation caused by the operation. We find that a natural extension of
      the minimum work principle involves information about the time-reversed
      operation, and is far from straightforward. Our work relation may be tested
      experimentally especially when the temperature gradient is small.

PMID- 23004712
TI  - Onset of synchronization in complex networks of noisy oscillators.
AB  - We study networks of noisy phase oscillators whose nodes are characterized by
      random degrees counting the number of their connections. Both these degrees and
      the natural frequencies of the oscillators are distributed according to a given
      probability density. Replacing the randomly connected network by an all-to-all
      coupled network with weighted edges allows us to formulate the dynamics of a
      single oscillator coupled to the mean field and to derive the corresponding
      Fokker-Planck equation. From the latter we calculate the critical coupling
      strength for the onset of synchronization as a function of the noise intensity,
      the frequency distribution, and the first two moments of the degree distribution.
      Our approach is applied to a dense small-world network model, for which we
      calculate the degree distribution. Numerical simulations prove the validity of
      the replacement. We also test the applicability to more sparsely connected
      networks and formulate homogeneity and absence of correlations in the degree
      distribution as limiting factors of our approach.

PMID- 23004713
TI  - Virtual qubits, virtual temperatures, and the foundations of thermodynamics.
AB  - We argue that thermal machines can be understood from the perspective of "virtual
      qubits" at "virtual temperatures": The relevant way to view the two heat baths
      which drive a thermal machine is as a composite system. Virtual qubits are two
      level subsystems of this composite, and their virtual temperatures can take on
      any value, positive or negative. Thermal machines act upon an external system by
      placing it in thermal contact with a well-selected range of virtual qubits and
      temperatures. We demonstrate these claims by studying the smallest thermal
      machines. We show further that this perspective provides a powerful way to view
      thermodynamics, by analyzing a number of phenomena. This includes approaching
      Carnot efficiency (where we find that all machines do so essentially by becoming
      equivalent to the smallest thermal machines), entropy production in irreversible
      machines, and a way to view work in terms of negative temperature and population
      inversion. Moreover we introduce the idea of "genuine" thermal machines and are
      led to considering the concept of "strength" of work.

PMID- 23004714
TI  - Explosive percolation on the Bethe lattice.
AB  - Based on self-consistent equations of the order parameter Pinfinity and the mean
      cluster size S, we develop a self-consistent simulation method for arbitrary
      percolation on the Bethe lattice (infinite homogeneous Cayley tree). By applying
      the self-consistent simulation to well-known percolation models, random bond
      percolation, and bootstrap percolation, we obtain prototype functions for
      continuous and discontinuous phase transitions. By comparing key functions
      obtained from self-consistent simulations for Achlioptas models with a product
      rule and a sum rule to the prototype functions, we show that the percolation
      transition of Achlioptas models on the Bethe lattice is continuous regardless of
      details of growth rules.

PMID- 23004715
TI  - Dynamical scaling behavior of the one-dimensional conserved directed-percolation
      universality class.
AB  - We investigate the dynamical scaling behavior of the static diffusive epidemic
      process and a fixed-energy Manna sandpile model, undergoing nonequilibrium
      absorbing phase transitions in one dimension. These models belong to the so
      called conserved directed-percolation or Manna universality class characterized
      by the conservation of the total particle number, activity coupled to a
      nondiffusive conserved field and infinitely many absorbing states. We measure the
      dynamical exponents of these models in one dimension by using the critical
      spreading simulation of a localized activity in absorbing configurations. In the
      spreading simulations, boundaries are never touched, so the results are free from
      the finite-size effects. In contrast to the scattered results for the different
      models from the previous finite-size scaling analyses, we obtain consistent
      estimates of the dynamical exponents for both models.

PMID- 23004716
TI  - Strongly anisotropic nonequilibrium phase transition in Ising models with
      friction.
AB  - The nonequilibrium phase transition in driven two-dimensional Ising models with
      two different geometries is investigated using Monte Carlo methods as well as
      analytical calculations. The models show dissipation through fluctuation induced
      friction near the critical point. We first consider high driving velocities and
      demonstrate that both systems are in the same universality class and undergo a
      strongly anisotropic nonequilibrium phase transition, with anisotropy exponent
      theta=3. Within a field theoretical ansatz the simulation results are confirmed.
      The crossover from Ising to mean field behavior in dependency of system size and
      driving velocity is analyzed using crossover scaling. It turns out that for all
      finite velocities the phase transition becomes strongly anisotropic in the
      thermodynamic limit.

PMID- 23004717
TI  - Behavior of a single element in a finite stochastic array.
AB  - We describe statistical properties of a single element in a nonlinear stochastic
      array with a finite number of elements with mean-field-like (global) coupling.
      Desai and Zwanzig [J. Stat. Phys. 19, 1 (1978)] made use of a self-consistent
      dynamic mean-field ansatz to derive, in the infinite-size limit, a nonlinear
      Fokker-Planck equation (NLFPE) for the single-particle distribution function. In
      this work we explore the reliability of this approximation to describe a finite
      system with a small number of elements. We carry out a numerical analysis of the
      NLFPE as well as numerical simulations of the full set of Langevin equations
      governing the dynamics of the coupled elements. We find that for parameter values
      such that the NLFPE has a single stationary solution, it provides a reliable
      asymptotic approximation to the time evolution and stationary properties of a
      finite system of even modest size. In contrast, for parameter values such that
      the NLFPE has two stable stationary coexisting solutions, the NLFPE leads to
      results that are greatly at variance with those obtained from the numerical
      simulations of the Langevin equations for small systems.

PMID- 23004718
TI  - Phase transitions in trajectories of a superconducting single-electron transistor
      coupled to a resonator.
AB  - Recent progress in the study of dynamical phase transitions has been made with a
      large-deviation approach to study trajectories of stochastic jumps using a
      thermodynamic formalism. We study this method applied to an open quantum system
      consisting of a superconducting single-electron transistor, near the Josephson
      quasiparticle resonance, coupled to a resonator. We find that the dynamical
      behavior shown in rare trajectories can be rich even when the mean dynamical
      activity is small, and thus the formalism gives insights into the form of
      fluctuations. The structure of the dynamical phase diagram found from the quantum
      jump trajectories of the resonator is studied, and we see that sharp transitions
      in the dynamical activity may be related to the appearance and disappearance of
      bistabilities in the state of the resonator as system parameters are changed. We
      also demonstrate that for a fast resonator, the trajectories of quasiparticles
      are similar to the resonator trajectories.

PMID- 23004719
TI  - Nonequilibrium phase transitions and stationary-state solutions of a three
      dimensional random-field Ising model under a time-dependent periodic external
      field.
AB  - Nonequilibrium behavior and dynamic phase-transition properties of a kinetic
      Ising model under the influence of periodically oscillating random fields have
      been analyzed within the framework of effective-field theory based on a
      decoupling approximation. A dynamic equation of motion has been solved for a
      simple-cubic lattice (q=6) by utilizing a Glauber-type stochastic process.
      Amplitude of the sinusoidally oscillating magnetic field is randomly distributed
      on the lattice sites according to bimodal and trimodal distribution functions.
      For a bimodal type of amplitude distribution, it is found in the high-frequency
      regime that the dynamic phase diagrams of the system in the temperature versus
      field amplitude plane resemble the corresponding phase diagrams of the pure
      kinetic Ising model. Our numerical results indicate that for a bimodal
      distribution, both in the low- and high-frequency regimes, the dynamic phase
      diagrams always exhibit a coexistence region in which the stationary state (ferro
      or para) of the system is completely dependent on the initial conditions, whereas
      for a trimodal distribution, the coexistence region disappears depending on the
      values of the system parameters.

PMID- 23004720
TI  - Superaging correlation function and ergodicity breaking for Brownian motion in
      logarithmic potentials.
AB  - We consider an overdamped Brownian particle moving in a confining asymptotically
      logarithmic potential, which supports a normalized Boltzmann equilibrium density.
      We derive analytical expressions for the two-time correlation function and the
      fluctuations of the time-averaged position of the particle for large but finite
      times. We characterize the occurrence of aging and nonergodic behavior as a
      function of the depth of the potential, and we support our predictions with
      extensive Langevin simulations. While the Boltzmann measure is used to obtain
      stationary correlation functions, we show how the non-normalizable infinite
      covariant density is related to the superaging behavior.

PMID- 23004721
TI  - Temporal disorder in up-down symmetric systems.
AB  - The effect of temporal disorder on systems with up-down Z_{2} symmetry is
      studied. In particular, we analyze two well-known families of phase transitions
      the Ising and the generalized voter universality classes-and scrutinize the
      consequences of placing them under fluctuating global conditions. We observe that
      variability of the control parameter induces in both classes "temporal Griffiths
      phases" (TGPs). These recently uncovered phases are analogous to standard
      Griffiths phases appearing in systems with quenched spatial disorder, but where
      the roles of space and time are exchanged. TGPs are characterized by broad
      regions in parameter space in which (i) mean first-passage times scale
      algebraically with system size, and (ii) the system response (e.g.,
      susceptibility) diverges. Our results confirm that TGPs are quite robust and
      ubiquitous in the presence of temporal disorder. Possible applications of our
      results to examples in ecology are discussed.

PMID- 23004722
TI  - Scaling exponents for a monkey on a tree: fractal dimensions of randomly branched
      polymers.
AB  - We study asymptotic properties of diffusion and other transport processes
      (including self-avoiding walks and electrical conduction) on large, randomly
      branched polymers using renormalized dynamical field theory. We focus on the
      swollen phase and the collapse transition, where loops in the polymers are
      irrelevant. Here the asymptotic statistics of the polymers is that of lattice
      trees, and diffusion on them is reminiscent of the climbing of a monkey on a
      tree. We calculate a set of universal scaling exponents including the diffusion
      exponent and the fractal dimension of the minimal path to two-loop order and,
      where available, compare them to numerical results.

PMID- 23004723
TI  - Statistical description of the collective motion of nanoparticles.
AB  - A synergetic model allowing the description of a Brownian motion of active
      nanoparticles within the framework of the Lorenz three-parameter system is
      developed. The fluctuation's influence on the transition between different motion
      regimes is investigated. A diagram of possible motion modes of an active
      nanoparticle group and the corresponding stationary values of velocity are
      analyzed.

PMID- 23004724
TI  - Upper transition point for percolation on the enhanced binary tree: a sharpened
      lower bound.
AB  - Hyperbolic structures are obtained by tiling a hyperbolic surface with negative
      Gaussian curvature. These structures generally exhibit two percolation
      transitions: a system-wide connection can be established at a certain occupation
      probability p = pc1, and there emerges a unique giant cluster at pc2 > pc1. There
      have been debates about locating the upper transition point of a prototypical
      hyperbolic structure called the enhanced binary tree (EBT), which is constructed
      by adding loops to a binary tree. This work presents its lower bound as pc2 ?
      0.55 by using phenomenological renormalization-group methods and discusses some
      solvable models related to the EBT.

PMID- 23004725
TI  - Wigner separability entropy and complexity of quantum dynamics.
AB  - We propose the Wigner separability entropy as a measure of complexity of a
      quantum state. This quantity measures the number of terms that effectively
      contribute to the Schmidt decomposition of the Wigner function with respect to a
      chosen phase-space decomposition. We prove that the Wigner separability entropy
      is equal to the operator space entanglement entropy, measuring entanglement in
      the space of operators, and, for pure states, twice the entropy of entanglement.
      The quantum to classical correspondence between the Wigner separability entropy
      and the separability entropy of the classical phase-space Liouville density is
      illustrated by means of numerical simulations of chaotic maps. In this way, the
      separability entropy emerges as an extremely broad complexity quantifier in both
      the classical and quantum realms.

PMID- 23004726
TI  - Resonant response in nonequilibrium steady states.
AB  - The time-dependent probability density function of the order parameter of a
      system evolving toward a stationary state exhibits an oscillatory behavior if the
      eigenvalues of the corresponding evolution operator are complex. The frequencies
      omegan, with which the system reaches its stationary state, correspond to the
      imaginary part of such eigenvalues. If the system (at the stationary state) is
      further driven by a small and oscillating perturbation with a given frequency
      omega, we formally prove that the linear response to the probability density
      function is enhanced when omega=omegan for n?N. We prove that the occurrence of
      this phenomenon is characteristic of systems that are in a nonequilibrium
      stationary state. In particular, we obtain an explicit formula for the frequency
      dependent mobility in terms of the relaxation to the stationary state of the
      (unperturbed) probability current. We test all these predictions by means of
      numerical simulations considering an ensemble of noninteracting overdamped
      particles on a tilted periodic potential.

PMID- 23004727
TI  - Fractional Brownian motors and stochastic resonance.
AB  - We study fluctuating tilt Brownian ratchets based on fractional subdiffusion in
      sticky viscoelastic media characterized by a power law memory kernel. Unlike the
      normal diffusion case, the rectification effect vanishes in the adiabatically
      slow modulation limit and optimizes in a driving frequency range. It is shown
      also that the anomalous rectification effect is maximal (stochastic resonance
      effect) at optimal temperature and can be of surprisingly good quality. Moreover,
      subdiffusive current can flow in the counterintuitive direction upon a change of
      temperature or driving frequency. The dependence of anomalous transport on load
      exhibits a remarkably simple universality.

PMID- 23004728
TI  - Transition by breaking of analyticity in the ground state of Josephson junction
      arrays as a static signature of the vortex jamming transition.
AB  - We investigate the ground state of the irrationally frustrated Josephson junction
      array with a controlling anisotropy parameter lambda that is the ratio of the
      longitudinal Josephson coupling to the transverse one. We find that the ground
      state has one-dimensional periodicity whose reciprocal lattice vector depends on
      lambda and is incommensurate with the substrate lattice. Approaching the
      isotropic point lambda=1, the so-called hull function of the ground state
      exhibits analyticity breaking similar to the Aubry transition in the Frenkel
      Kontorova model. We find a scaling law for the harmonic spectrum of the hull
      functions, which suggests the existence of a characteristic length scale
      diverging at the isotropic point. This critical behavior is directly connected to
      the jamming transition previously observed in the current-voltage characteristics
      by a numerical simulation. On top of the ground state there is a gapless
      continuous band of metastable states, which exhibit the same critical behavior as
      the ground state.

PMID- 23004729
TI  - Information metric from a linear sigma model.
AB  - The idea that a space-time metric emerges as a Fisher-Rao "information metric" of
      instanton moduli space has been examined in several field theories, such as the
      Yang-Mills theories and nonlinear sigma models. In this paper, we report that the
      flat Euclidean or Minkowskian metric, rather than an anti-de Sitter metric that
      generically emerges from instanton moduli spaces, can be obtained as the Fisher
      Rao metric from a nontrivial solution of the massive Klein-Gordon field (a linear
      sigma model). This realization of the flat space from the simple field theory
      would be useful to investigate the ideas that relate the space-time geometry with
      the information geometry.

PMID- 23004730
TI  - Detection of diffusion anisotropy due to particle asymmetry from single-particle
      tracking of Brownian motion by the large-deviation principle.
AB  - We show that the diffusion anisotropy due to the asymmetry of the particle can be
      extracted from the trajectory data without the information of the particle
      orientation. The subject of analysis is typical in single-particle tracking (SPT)
      experiments, and the analysis is based on the large-deviation principle in
      mathematics. We consider the model system of Langevin equations in two dimensions
      where a particle diffusion shows anisotropy depending on a single parameter
      defined by the two diffusion coefficients in the perpendicular directions of the
      frame fixed to the particle. We show how the large-deviation quantities depend on
      this parameter so that it can be used for the detection of the diffusion
      anisotropy. We also illustrate how the discreteness of the sampling interval in
      the SPT and the finiteness of the number of samples influence the results of the
      analysis.

PMID- 23004731
TI  - Two-dimensional XXZ-Ising model with quartic interactions.
AB  - In this work we study a two-dimensional XXZ-Ising spin-1/2 model with quartic
      interactions. The model is composed of a two-dimensional lattice of edge-sharing
      unitary cells, where each cell consists of two triangular prisms, converging in a
      basal plane with four Ising spin-1/2 (open circles); the apical positions are
      also occupied by four Heisenberg spin-1/2 (solid circles). Interaction of the
      base plane containing the multispin Ising interaction has the parameter J_{4},
      and the other pairwise interactions have parameter J. For the proposed model we
      construct the phase diagram at zero temperature and give all possible spin
      configurations. In addition, we investigate two regions where the model can be
      solved exactly, the free fermion condition (FFC) and the symmetrical eight-vertex
      condition (SEVC). For this purpose we perform a straightforward mapping for a
      zero-field eight-vertex model. The necessary conditions for the equivalence are
      analyzed for all ranges of the interaction parameters. Unfortunately, the present
      model does not satisfy the FFC unless the trivial case; however, it was possible
      to give a region where the model can be solved approximately. We study the SEVC
      and verify that this condition is always satisfied. We also explore and discuss
      the critical conditions giving the region where these critical points are
      relevant.

PMID- 23004585
TI  - Search for a light Higgs boson decaying to long-lived weakly interacting
      particles in proton-proton collisions at sqrt[s] = 7 TeV with the ATLAS detector.
AB  - A search for the decay of a light Higgs boson (120-140 GeV) to a pair of weakly
      interacting, long-lived particles in 1.94 fb(-1) of proton-proton collisions at
      sqrt[s] = 7 TeV recorded in 2011 by the ATLAS detector is presented. The search
      strategy requires that both long-lived particles decay inside the muon
      spectrometer. No excess of events is observed above the expected background and
      limits on the Higgs boson production times branching ratio to weakly interacting,
      long-lived particles are derived as a function of the particle proper decay
      length.

PMID- 23004732
TI  - Predictability of the coherent-noise model and its applications.
AB  - We study the threshold distribution function of the coherent-noise model for the
      case of infinite number of agents. This function is piecewise constant with a
      finite number of steps n. The latter exhibits a 1/f behavior as a function of the
      order of occurrence of an avalanche and hence versus natural time. An analytic
      expression of the expectation value E(S) for the size S of the next avalanche is
      obtained and used for the prediction of the next avalanche. Apart from E(S), the
      number of steps n can also serve for this purpose. This enables the construction
      of a similar prediction scheme which can be applied to real earthquake aftershock
      data.

PMID- 23004733
TI  - Surface-directed spinodal decomposition: a molecular dynamics study.
AB  - We use molecular dynamics simulations to study surface-directed spinodal
      decomposition in unstable binary AB fluid mixtures at wetting surfaces. The
      thickness of the wetting layer R1 grows with time t as a power law (R1~ttheta).
      We find that hydrodynamic effects result in a crossover of the growth exponent
      from theta?1/3 to 1. We also present results for the layerwise correlation
      functions and domain length scales.

PMID- 23004735
TI  - Estimation of the entropy based on its polynomial representation.
AB  - Estimating entropy from empirical samples of finite size is of central importance
      for information theory as well as the analysis of complex statistical systems.
      Yet, this delicate task is marred by intrinsic statistical bias. Here we
      decompose the entropy function into a polynomial approximation function and a
      remainder function. The approximation function is based on a Taylor expansion of
      the logarithm. Given n observations, we give an unbiased, linear estimate of the
      first n power series terms based on counting sets of k coincidences. For the
      remainder function we use nonlinear Bayesian estimation with a nearly flat prior
      distribution on the entropy that was developed by Nemenman, Shafee, and Bialek.
      Our simulations show that the combined entropy estimator has reduced bias in
      comparison to other available estimators.

PMID- 23004737
TI  - Crossing on hyperbolic lattices.
AB  - We divide the circular boundary of a hyperbolic lattice into four equal intervals
      and study the probability of a percolation crossing between an opposite pair as a
      function of the bond occupation probability p. We consider the {7,3}
      (heptagonal), enhanced or extended binary tree (EBT), the EBT-dual, and the {5,5}
      (pentagonal) lattices. We find that the crossing probability increases gradually
      from 0 to 1 as p increases from the lower p_{l} to the upper p_{u} critical
      values. We find bounds and estimates for the values of p_{l} and p_{u} for these
      lattices and identify the self-duality point p corresponding to where the
      crossing probability equals 1/2. Comparison is made with recent numerical and
      theoretical results.

PMID- 23004738
TI  - Full-counting statistics of heat transport in harmonic junctions: transient,
      steady states, and fluctuation theorems.
AB  - We study the statistics of heat transferred in a given time interval t_{M},
      through a finite harmonic chain, called the center, which is connected to two
      heat baths, the left (L) and the right (R), that are maintained at two
      temperatures. The center atoms are driven by external time-dependent forces. We
      calculate the cumulant generating function (CGF) for the heat transferred out of
      the left lead, Q_{L}, based on the two-time quantum measurement concept and using
      the nonequilibrium Green's function method. The CGF can be concisely expressed in
      terms of Green's functions of the center and an argument-shifted self-energy of
      the lead. The expression of the CGF is valid in both transient and steady-state
      regimes. We consider three initial conditions for the density operator and show
      numerically, for a one-atom junction, how their transient behaviors differ from
      each other but, finally, approach the same steady state, independent of the
      initial distributions. We also derive the CGF for the joint probability
      distribution P(Q_{L},Q_{R}), and discuss the correlations between Q_{L} and
      Q_{R}. We calculate the CGF for total entropy production in the reservoirs. In
      the steady state we explicitly show that the CGFs obey steady-state fluctuation
      theorems. We obtain classical results by taking h->0. We also apply our method to
      the counting of the electron number and electron energy, for which the associated
      self-energy is obtained from the usual lead self-energy by multiplying a phase
      and shifting the contour time, respectively.

PMID- 23004736
TI  - Microstructural degeneracy associated with a two-point correlation function and
      its information content.
AB  - A two-point correlation function provides a crucial yet an incomplete
      characterization of a microstructure because distinctly different microstructures
      may have the same correlation function. In an earlier Letter [Gommes, Jiao, and
      Torquato, Phys. Rev. Lett. 108, 080601 (2012)], we addressed the microstructural
      degeneracy question: What is the number of microstructures compatible with a
      specified correlation function? We computed this degeneracy, i.e.,
      configurational entropy, in the framework of reconstruction methods, which
      enabled us to map the problem to the determination of ground-state degeneracies.
      Here, we provide a more comprehensive presentation of the methodology and
      analyses, as well as additional results. Since the configuration space of a
      reconstruction problem is a hypercube on which a Hamming distance is defined, we
      can calculate analytically the energy profile of any reconstruction problem,
      corresponding to the average energy of all microstructures at a given Hamming
      distance from a ground state. The steepness of the energy profile is a measure of
      the roughness of the energy landscape associated with the reconstruction problem,
      which can be used as a proxy for the ground-state degeneracy. The relationship
      between this roughness metric and the ground-state degeneracy is calibrated using
      a Monte Carlo algorithm for determining the ground-state degeneracy of a variety
      of microstructures, including realizations of hard disks and Poisson point
      processes at various densities as well as those with known degeneracies (e.g.,
      single disks of various sizes and a particular crystalline microstructure). We
      show that our results can be expressed in terms of the information content of the
      two-point correlation functions. From this perspective, the a priori condition
      for a reconstruction to be accurate is that the information content, expressed in
      bits, should be comparable to the number of pixels in the unknown microstructure.
      We provide a formula to calculate the information content of any two-point
      correlation function, which makes our results broadly applicable to any field in
      which correlation functions are employed.

PMID- 23004739
TI  - Widom line and noise-power spectral analysis of a supercritical fluid.
AB  - We have performed extensive molecular dynamics simulations to study noise-power
      spectra of density and potential energy fluctuations of a Lennard-Jones model of
      a fluid in the supercritical region. Emanating from the liquid-vapor critical
      point, there is a locus of isobaric specific heat maxima, called the Widom line,
      which is often regarded as an extension of the liquid-vapor coexistence line. Our
      simulation results show that the noise-power spectrum of the density fluctuations
      on the Widom line of the liquid-vapor transition exhibits three distinct
      1/f^{gamma} behaviors with exponents gamma=0, 1.2, and 2, depending on the
      frequency f. We find that the intermediate frequency region with an exponent
      gamma~ 1 appears as the temperature approaches the Widom temperature from above
      or below. On the other hand, we do not find three distinct regions of 1/f^{gamma}
      in the power spectrum of the potential energy fluctuations on the Widom line.
      Furthermore, we find that the power spectra of both the density and potential
      energy fluctuations at low frequency have a maximum on the Widom line, suggesting
      that the noise power can provide an alternative signature of the Widom line.

PMID- 23004734
TI  - Scaling theory for the quasideterministic limit of continuous bifurcations.
AB  - Deterministic rate equations are widely used in the study of stochastic,
      interacting particles systems. This approach assumes that the inherent noise,
      associated with the discreteness of the elementary constituents, may be neglected
      when the number of particles N is large. Accordingly, it fails close to the
      extinction transition, when the amplitude of stochastic fluctuations is
      comparable with the size of the population. Here we present a general scaling
      theory of the transition regime for spatially extended systems. We demonstrate
      this through a detailed study of two fundamental models for out-of-equilibrium
      phase transitions: the Susceptible-Infected-Susceptible (SIS) that belongs to the
      directed percolation equivalence class and the Susceptible-Infected-Recovered
      (SIR) model belonging to the dynamic percolation class. Implementing the Ginzburg
      criteria we show that the width of the fluctuation-dominated region scales like
      N^{-kappa}, where N is the number of individuals per site and kappa=2/(d_{u}-d),
      d_{u} is the upper critical dimension. Other exponents that control the approach
      to the deterministic limit are shown to be calculable once kappa is known. The
      theory is extended to include the corrections to the front velocity above the
      transition. It is supported by the results of extensive numerical simulations for
      systems of various dimensionalities.

PMID- 23004740
TI  - Nanoscale simple-fluid behavior under steady shear.
AB  - In this study, we use two nonequilibrium molecular dynamics algorithms, boundary
      driven shear and homogeneous shear, to explore the rheology and flow properties
      of a simple fluid undergoing steady simple shear. The two distinct algorithms are
      designed to elucidate the influences of nanoscale confinement. The results of
      rheological material functions, i.e., viscosity and normal pressure differences,
      show consistent Newtonian behaviors at low shear rates from both systems. The
      comparison validates that confinements of the order of 10 nm are not strong
      enough to deviate the simple fluid behaviors from the continuum hydrodynamics.
      The non-Newtonian phenomena of the simple fluid are further investigated by the
      homogeneous shear simulations with much higher shear rates. We observe the
      "string phase" at high shear rates by applying both profile-biased and profile
      unbiased thermostats. Contrary to other findings where the string phase is found
      to be an artifact of the thermostats, we perform a thorough analysis of the fluid
      microstructures formed due to shear, which shows that it is possible to have a
      string phase and second shear thinning for dense simple fluids.

PMID- 23004741
TI  - Structure and phase behavior of two-Yukawa fluids with competing interactions in
      planar slit pores.
AB  - A density functional perturbation theory, which is based both on the modified
      fundamental-measure theory and on the first-order mean-spherical approximation
      for long-range attractive and repulsive interactions, has been developed for
      studying the structure and phase behaviors of a competing system restricted to
      slit pores. The hysteresis loop for the adsorption and desorption curves
      indicates that the system exhibits vapor-cluster and cluster-liquid transitions
      which depend on the pair potential parameters and the slit width (H). The
      periodic spacing (D) of the cluster is commensurate with the periodicity of
      modulation in the particle density distribution and more closely related to the
      vapor-cluster and cluster-liquid phase transitions of the system. For the cluster
      phase, we find the transition from a single liquidlike slab to a multi-liquidlike
      slab with increasing the slit width. The multi-liquidlike slab is formed
      depending on the periodicity of modulation by finite-size artifacts. The cluster
      related phase transitions, such as the vapor-cluster or cluster-liquid
      transitions occur for H>D, while for H<D the system only exhibits the vapor
      liquid transition. At a low amplitude, the vapor-liquid transition disappears and
      the cluster-liquid transition only occurs for H<D. The coexistence curves for the
      confined phase diagram are contained within the corresponding bulk liquid-vapor
      coexistence curve. For a wide slit pore (H>D), the system exhibits two
      tricritical points, joined to one another by the line of second-order transition.
      The results support the conclusion that the confinement effect plays an important
      role in determining the equilibrium phase transition.

PMID- 23004742
TI  - Nonexponential relaxation in a simple liquid metal.
AB  - A hallmark of the changes in dynamics towards the glass transition is the
      stretched exponential structural relaxation. Quasielastic neutron scattering
      results on liquid rubidium demonstrate such a nonexponential relaxation process
      in a simple liquid metal above the melting point. The nonexponential decay is an
      indication of non-Markovian dynamics and points to the collective character of
      the relaxation process. Describing the relaxation dynamics by a two-step process,
      the long lasting part of the decay process is in remarkable quantitative
      agreement with predictions from mode coupling theory. The feedback mechanism of
      the slowing down process in the theoretical description suggests that this
      contribution is at the origin of the structural arrest. With rising temperature
      the intermediate scattering function transforms into a simple exponential decay
      at a temperature range which indicates the end of the highly viscous solidlike
      behavior in the liquid.

PMID- 23004743
TI  - Combining molecular dynamics simulation and transition state theory to evaluate
      solid-liquid interfacial friction in carbon nanotube membranes.
AB  - A molecular dynamics (MD) methodology based on Eyring theory of reaction rates is
      proposed for investigating solid-liquid interfacial properties crucial to the
      development of many nanotechnology applications. The method involves the
      calculation of activation energy required for the flow process directly from the
      MD trajectory information. We have applied this methodology to study the behavior
      of water in hydrophobic confinement in carbon nanotubes (CNTs) and also between
      graphene sheets. In the case of confined water molecules in CNTs and between
      graphene sheets the degree of confinement and curvature effects were found to
      have more influence on the solid-liquid interfacial friction, with almost
      negligible friction below a certain characteristic dimension in both the cases.
      This behavior of confined and unconfined water molecules is explained on the
      basis of molecular interactions and subsequent changes in the activation energy.
      Analysis based on this method also revealed that a finite amount of friction does
      exist at the channel entry and exit region. This could limit the flow of liquid
      molecules through the nanochannels and hence needs to be taken into account in
      the design of nanofluidic devices.

PMID- 23004744
TI  - Universal reference state in a driven homogeneous granular gas.
AB  - We study the dynamics of a homogeneous granular gas heated by a stochastic
      thermostat, in the low density limit. It is found that, before reaching the
      stationary regime, the system quickly "forgets" the initial condition and then
      evolves through a universal state that does not only depend on the dimensionless
      velocity, but also on the instantaneous temperature, suitably renormalized by its
      steady state value. We find excellent agreement between the theoretical
      predictions at the Boltzmann equation level for the one-particle distribution
      function and the direct Monte Carlo simulations. We conclude that at variance
      with the homogeneous cooling phenomenology, the velocity statistics should not be
      envisioned as a single-parameter, but as a two-parameter scaling form, keeping
      track of the distance to stationarity.

PMID- 23004745
TI  - Probing the shear-band formation in granular media with sound waves.
AB  - We investigate the mechanical responses of dense granular materials, using a
      direct shear box combined with simultaneous acoustic measurements. Measured shear
      wave speeds evidence the structural change of the material under shear, from the
      jammed state to the flowing state. There is a clear acoustic signature when the
      shear band is formed. Subjected to cyclic shear, both shear stress and wave speed
      show the strong hysteretic dependence on the shear strain, likely associated with
      the geometry change in the packing structure. Moreover, the correlation function
      of configuration-specific multiply scattered waves reveals an intermittent
      behavior before the failure of material.

PMID- 23004746
TI  - Microscopic dissipation in a cohesionless granular jet impact.
AB  - Sufficiently fine granular systems appear to exhibit continuum properties, though
      the precise continuum limit obtained can be vastly different depending on the
      particular system. In the present paper the continuum limit of an unconfined,
      dense granular flow is investigated. To do this a two-dimensional dense
      cohesionless granular jet impinging upon a target is used as a test system. This
      is simulated via a time-step-driven hard-sphere method and apply a mean-field
      theoretical approach to connect the macroscopic flow with the microscopic
      material parameters of the grains. It is observed that the flow separates into a
      cone with an interior cone angle determined by the conservation of momentum and
      the dissipation of energy. From the cone angle a dimensionless quantity A-B that
      characterizes the flow is extracted. This quantity is found to depend both on
      whether or not a dead zone, i.e., a stationary region near the target, is present
      and on the value of the coefficient of dynamic friction. A theory is presented
      for the scaling of A-B with the coefficient of friction that suggests that
      dissipation is primarily a perturbative effect in this flow rather than the
      source of qualitatively different behavior.

PMID- 23004747
TI  - Expression for the granular elastic energy.
AB  - Granular solid hydrodynamics (GSH) is a broad-ranged continual mechanical
      description of granular media capable of accounting for static stress
      distributions, yield phenomena, propagation and damping of elastic waves, the
      critical state, shear band, and fast dense flow. An important input of GSH is an
      expression for the elastic energy needed to deform the grains. The original
      expression, though useful and simple, has some drawbacks. Therefore a slightly
      more complicated expression is proposed here that eliminates three of them: (1)
      The maximal angle at which an inclined layer of grains remains stable is
      increased from 26^{?} to the more realistic value of 30^{?}. (2) Depending on
      direction and polarization, transverse elastic waves are known to propagate at
      slightly different velocities. The old expression neglects these differences, the
      new one successfully reproduces them. (3) Most importantly, the old expression
      contains only the Drucker-Prager yield surface. The new one contains in addition
      those named after Coulomb, Lade-Duncan, and Matsuoka-Nakai-realizing each, and
      interpolating between them, by shifting a single scalar parameter.

PMID- 23004748
TI  - Dense packings of spheres in cylinders: simulations.
AB  - We study the optimal packing of hard spheres in an infinitely long cylinder,
      using simulated annealing, and compare our results with the analogous problem of
      packing disks on the unrolled surface of a cylinder. The densest structures are
      described and tabulated in detail up to D/d=2.873 (ratio of cylinder and sphere
      diameters). This extends previous computations into the range of structures which
      include internal spheres that are not in contact with the cylinder.

PMID- 23004749
TI  - Evolution of the primary pulse in one-dimensional granular crystals subject to on
      site perturbations: analytical study.
AB  - The propagation of the primary pulse through an uncompressed granular chain
      subject to external on-site perturbation is studied. An analytical procedure
      predicting the evolution of the primary pulse is devised for the general form of
      the on-site perturbation applied on the chain. The validity of the analytical
      model is confirmed with several specific granular setups, such as chains mounted
      on the nonlinear elastic foundation, chains perturbed by the dissipative forces,
      as well as randomly perturbed chains. An additional interesting finding made in
      the present paper corresponds to the chains subject to a special type of
      perturbation, including the terms leading to dissipation and those acting as an
      energy source. In the paper, it is shown that an application of such a
      perturbation may lead to the formation of stable stationary primary pulses
      propagating with constant amplitudes and acting as attractors for the initially
      unperturbed Nesterenko solitary waves. Interestingly enough, the developed
      analytical procedure provides an extremely close estimation for the amplitudes of
      these stationary primary pulses as well as predicts zones of their stability. In
      conclusion, we would like to stress that the developed analytical model has
      demonstrated spectacular agreement with the results of the direct numerical
      simulations, and this is for various configurations considered in the current
      paper.

PMID- 23004750
TI  - Strong interlocking of nonconvex particles in random packings.
AB  - We present a numerical study of random packings made of nonconvex grains. These
      particles are built by the agglomeration of overlapping spheres in order to
      control their sphericity phi. The contact number C is found to be much larger
      than the coordination number Z, providing a significant difference with convex
      grains. The packing properties are found to be highly dependent on the
      morphological parameters of the grains : packing fractions as low as 0.3 have
      been reached. More importantly, the way nonconvex grains develop multiple
      contacts, i.e., interlocking, is found to be a relevant effect in such packings.
      Interlocking provides more stability to loose packings.

PMID- 23004751
TI  - Collapse of granular-liquid mixtures over rigid, inclined beds.
AB  - This work deals with the propagation of granular-liquid waves over rigid beds,
      originated by the sudden removal of a sluice gate in a rectangular, inclined
      flume. In particular, we experimentally investigate the role of the initial
      volume ratio of granular material-monodispersed plastic cylinders-to water, the
      flume width, and the bed roughness on the time evolution of the granular front.
      Due to the presence of the interstitial liquid, we observed previously unreported
      types of collapse: (i) discontinuous flows, where the granular material stops
      after an initial spreading, and then flows again when the liquid, initially
      slower than the particles, reaches the front and remobilizes it; (ii) flows
      evolving into uniformly progressive waves at an angle of inclination of the flume
      well below the angle of repose of the dry granular material. We also noticed an
      unusual influence of the lateral confinement on the wave propagation. Indeed, the
      constant front velocity in the uniformly progressive state decreases when the
      channel width increases. We claim that the latter observation and the presence of
      discontinuous flows, strongly support the idea that only two-phase, stratified
      mathematical models can predict the behavior of unsteady, granular-liquid
      mixtures at high concentration, such as debris flows.

PMID- 23004752
TI  - Relation between self-organized criticality and grain aspect ratio in granular
      piles.
AB  - We investigate experimentally whether self-organized criticality (SOC) occurs in
      granular piles composed of different grains, namely, rice, lentils, quinoa, and
      mung beans. These four grains were selected to have different aspect ratios, from
      oblong to oblate. As a function of aspect ratio, we determined the growth (beta)
      and roughness (alpha) exponents, the avalanche fractal dimension (D), the
      avalanche size distribution exponent (tau), the critical angle (gamma), and its
      fluctuation. At superficial inspection, three types of grains seem to have power
      law-distributed avalanches with a well-defined tau. However, only rice is truly
      SOC if we take three criteria into account: a power-law-shaped avalanche size
      distribution, finite size scaling, and a universal scaling relation relating
      characteristic exponents. We study SOC as a spatiotemporal fractal; in
      particular, we study the spatial structure of criticality from local observation
      of the slope angle. From the fluctuation of the slope angle we conclude that
      greater fluctuation (and thus bigger avalanches) happen in piles consisting of
      grains with larger aspect ratio.

PMID- 23004753
TI  - How does an ice block assembly melt?
AB  - The melting of an assembly of ice blocks contained in a vertical cylinder and
      under an unidirectional load was investigated. The total volume occupied by the
      ice blocks and the volume of ice were simultaneously measured which allowed one
      to determine the volume fraction of the ice in the cylinder. While the ice volume
      continuously decreases, sudden breakdowns of the total volume were observed.
      Large reorganizations of the whole assembly occur. However, the maximal volume
      fraction found just after a large reorganization decreased with time. In
      addition, the modifications of the pile structure were investigated using an x
      ray tomography imaging before and after one collapse. As the packing is better
      ordered along the walls, we suggest that the motion of the piston is governed by
      the layer of ice blocks located along the container wall. This layer was modeled
      by a two-dimensional assembly of disks. The model supports the idea that the
      geometrical frustrations explain the dynamics of the successive reorganization
      due to the shrinkage of the grains. Finally, numerical simulations allow one to
      conclude that the dynamics of the melting of the ice blocks is governed (i) by
      the confinement effect which induces defects in the packing and (ii) by the low
      friction between the ice blocks.

PMID- 23004754
TI  - X-ray microtomography study of the compaction process of rods under tapping.
AB  - We present an x-ray microtomography study of the compaction process of
      cylindrical rods under tapping. The process is monitored by measuring the
      evolution of the orientational order parameter, local, and overall packing
      densities as a function of the tapping number for different tapping intensities.
      The slow relaxation dynamics of the orientational order parameter can be well
      fitted with a stretched-exponential law with stretching exponents ranging from
      0.9 to 1.6. The corresponding relaxation time versus tapping intensity follows an
      Arrhenius behavior which is reminiscent of the slow dynamics in thermal glassy
      systems. We also investigated the boundary effect on the ordering process and
      found that boundary rods order faster than interior ones. In searching for the
      underlying mechanism of the slow dynamics, we estimated the initial random
      velocities of the rods under tapping and found that the ordering process is
      compatible with a diffusion mechanism. The average coordination number as a
      function of the tapping number at different tapping intensities has also been
      measured, which spans a range from 6 to 8.

PMID- 23004755
TI  - Statics and dynamics of Yukawa cluster crystals on ordered substrates.
AB  - We examine the statics and dynamics of particles with repulsive Yukawa
      interactions in the presence of a two-dimensional triangular substrate for
      fillings of up to 12 particles per potential minimum. We term the ordered states
      Yukawa cluster crystals and show that they are distinct from the colloidal
      molecular crystal states found at low fillings. As a function of substrate and
      interaction strength at fixed particle density we find a series of novel
      crystalline states that we characterize using the structure factor. For fillings
      greater than four, shell and ring structures form at each potential minimum and
      can exhibit sample-wide orientational order. A disordered state can appear
      between ordered states as the substrate strength varies. Under an external drive,
      the onsets of different orderings produce clear changes in the critical depinning
      force, including a peak effect phenomenon that has generally only previously been
      observed in systems with random substrates. We also find a rich variety of
      dynamic ordering transitions that can be observed via changes in the structure
      factor and features in the velocity-force curves. The dynamical states encompass
      a variety of moving structures including one-dimensional stripes, smectic
      ordering, polycrystalline states, triangular lattices, and symmetry locking
      states. Despite the complexity of the system, we identify several generic
      features of the dynamical phase transitions which we map out in a series of phase
      diagrams. Our results have implications for the structure and depinning of
      colloids on periodic substrates, vortices in superconductors and Bose-Einstein
      condensates, Wigner crystals, and dusty plasmas.

PMID- 23004756
TI  - Pressure and density scaling for colloid-polymer systems in the protein limit.
AB  - Grand canonical Monte Carlo and histogram reweighting techniques are used to
      study the fluid-phase behavior of an athermal system of colloids and nonadsorbing
      polymers on a fine lattice in the "protein limit," where polymer dimensions
      exceed those of the colloids. The main parameters are the chains' radius of
      gyration, R_{g}, the diameter of the colloids, sigma_{c}, and the monomer
      diameter, sigma_{s}. The phase behavior is controlled by the macroscopic size
      ratio, q_{r}=2R_{g}/sigma_{c}, and the microscopic size ratio,
      d=sigma_{s}/sigma_{c}. The latter ratio is found to play a significant role in
      determining the critical monomer concentration for q_{r}?4 and the critical
      colloid density for all chain lengths. However, the critical (osmotic) pressure
      is independent of the microscopic size ratio at all macroscopic size ratios
      studied. Quantitative agreement is observed between our simulation results and
      experimental data. We scale our results based on the polymer correlation length,
      which has previously been suggested to universally collapse these binodals
      [Bolhuis et al., Phys. Rev. Lett. 90, 068304 (2003); Fleer and Tuinier, Phys.
      Rev. E 76, 041802 (2007)]. While the density binodals exhibit universal
      characteristics along the low-colloid-density branch, such features are not
      present in the corresponding high-density phase. However, pressure binodals do
      collapse nicely under such a scaling, even far from the critical point, which
      allows us to produce a binodal curve whose shape is independent of either size
      ratio.

PMID- 23004757
TI  - Structure of finite sphere packings via exact enumeration: implications for
      colloidal crystal nucleation.
AB  - We analyze the geometric structure and mechanical stability of a complete set of
      isostatic and hyperstatic sphere packings obtained via exact enumeration. The
      number of nonisomorphic isostatic packings grows exponentially with the number of
      spheres N, and their diversity of structure and symmetry increases with
      increasing N and decreases with increasing hyperstaticity H=N_{c}-N_{ISO}, where
      N_{c} is the number of pair contacts and N_{ISO}=3N-6. Maximally contacting
      packings are in general neither the densest nor the most symmetric. Analyses of
      local structure show that the fraction f of nuclei with order compatible with the
      bulk (rhcp) crystal decreases sharply with increasing N due to a high propensity
      for stacking faults, five- and near-fivefold symmetric structures, and other
      motifs that preclude rhcp order. While f increases with increasing H, a
      significant fraction of hyperstatic nuclei for N as small as 11 retain non-rhcp
      structure. Classical theories of nucleation that consider only spherical nuclei,
      or only nuclei with the same ordering as the bulk crystal, cannot capture such
      effects. Our results provide an explanation for the failure of classical
      nucleation theory for hard-sphere systems of N?10 particles; we argue that in
      this size regime, it is essential to consider nuclei of unconstrained geometry.
      Our results are also applicable to understanding kinetic arrest and jamming in
      systems that interact via hard-core-like repulsive and short-ranged attractive
      interactions.

PMID- 23004758
TI  - Bilayer crystals of charged magnetic dipoles: structure and phonon spectrum.
AB  - We study the structure and phonon spectrum of a two-dimensional bilayer system of
      classical charged dipoles oriented perpendicular to the plane of the layers for
      equal density in each layer. This system can be tuned through six different
      crystalline phases by changing the interlayer separation or the charge and/or
      dipole moment of the particle. The presence of the charge on the dipole particles
      is responsible for the nucleation of five staggered phases and a disordered phase
      which are not found in the magnetic dipole bilayer system. These extra phases are
      a consequence of the competition between the repulsive Coulomb and the attractive
      dipole interlayer interaction. We present the phase diagram and determine the
      order of the phase transitions. The phonon spectrum of the system was calculated
      within the harmonic approximation, and a nonmonotonic behavior of the phonon
      spectrum is found as a function of the effective strength of the interparticle
      interaction. The stability of the different phases is determined.

PMID- 23004759
TI  - Role of the electrostatic depletion attraction on the structure of charged
      liposome-polymer mixtures.
AB  - The effect of adding charged nonadsorbing polymers to electrostatically
      structured suspensions of charged liposomes has been experimentally studied by
      means of light scattering techniques. The static structure factor of the mixtures
      is analyzed using two polymers of different sizes. As the polymer concentration
      increases, the main peak of the structure factor decreases and shows an important
      shift to larger values of the scattering vector. Such displacement is the
      consequence of the electrostatic-enhanced depletion attraction induced by the
      polymers that counteracts the electrostatic repulsion. For the shorter polymer,
      the system remains stable for all studied polymer concentrations. However, for
      the long polymer chains, the effective attraction induced at the highest polymer
      density studied is strong enough to destabilize the mixture. In this case, the
      aggregation of the liposomes leads to clusters of nearly linear morphology. The
      PRISM theory is employed to calculate the effective pair potential between
      liposomes. The theoretical predictions are able to support the experimental
      observations, and provide an explanation of the interplay between the
      electrostatic repulsive interaction and the depletion attraction. In particular,
      they show that the depletion attraction is especially long ranged, and is
      dominated by electrostatic effects rather than entropic.

PMID- 23004760
TI  - Yield behavior of colloidal aggregates due to combined tensile-bending loads.
AB  - In this contribution, the yield behavior of a strongly flocculated colloidal
      structure subjected to a tensile-bending load is micromechanically modeled. The
      yielding of a cluster is assumed to be triggered by the failure of one bond
      (critical bond) and accompanied by massive breakage of further bonds. Thus,
      identifying the position of the critical bond and evaluating its yield force are
      the main goals of this study. Interparticle bonds are considered as flexible
      nanoscale bridges which fail when the force applied on them reaches a critical
      value. The yield of the critical bonds can result from both tensile and bending
      stresses. By means of the yield stresses in the critical bonds, the yield force
      of the whole cluster can be calculated.

PMID- 23004761
TI  - Metastable-state dynamics of a liquid: a free-energy landscape study.
AB  - Using the time dependence of density fluctuations in a supercooled liquid
      obtained from the solutions of the equations of nonlinear fluctuating
      hydrodynamics (NFH), the evolution of the system in the free energy landscape is
      studied. A crossover from a continuous fluid type dynamics to that of hopping
      between different free energy minima is observed as the liquid is increasingly
      supercooled. We demonstrate that our results are also in agreement with
      equilibrium density functional analysis of the same system. The density field
      obtained in the numerical solution of the NFH equations are further analyzed to
      introduce complimentary density of voids in the supercooled liquid state and its
      static and dynamic correlations are computed. The nature of the relaxation of
      vacancy correlations are observed to be similar to that of the density
      fluctuations.

PMID- 23004762
TI  - Nonlinear response theory for Markov processes: simple models for glassy
      relaxation.
AB  - The theory of nonlinear response for Markov processes obeying a master equation
      is formulated in terms of time-dependent perturbation theory for the Green's
      functions and general expressions for the response functions up to third order in
      the external field are given. The nonlinear response is calculated for a model of
      dipole reorientations in an asymmetric double well potential, a standard model in
      the field of dielectric spectroscopy. The static nonlinear response is finite
      with the exception of a certain temperature T_{0} determined by the value of the
      asymmetry. In a narrow temperature range around T_{0}, the modulus of the
      frequency-dependent cubic response shows a peak at a frequency on the order of
      the relaxation rate and it vanishes for both low frequencies and high
      frequencies. At temperatures at which the static response is finite (lower and
      higher than T_{0}), the modulus is found to decay monotonously from the static
      limit to zero at high frequencies. In addition, results of calculations for a
      trap model with a Gaussian density of states are presented. In this case, the
      cubic response depends on the specific dynamical variable considered and also on
      the way the external field is coupled to the kinetics of the model. In
      particular, a set of different dynamical variables that gives rise to identical
      shapes of the linear susceptibility and only to different temperature
      dependencies of the relaxation times is considered. It is found that the
      frequency dependence of the nonlinear response functions, however, strongly
      depends on the particular choice of the variables. The results are discussed in
      the context of recent theoretical and experimental findings regarding the
      nonlinear response of supercooled liquids and glasses.

PMID- 23004763
TI  - Fragile-to-strong crossover coupled to the liquid-liquid transition in
      hydrophobic solutions.
AB  - Using discrete molecular dynamics simulations we study the relation between the
      thermodynamic and diffusive behaviors of a primitive model of aqueous solutions
      of hydrophobic solutes consisting of hard spheres in the Jagla particles solvent,
      close to the liquid-liquid critical point of the solvent. We find that the
      fragile-to-strong dynamic transition in the diffusive behavior is always coupled
      to the low-density-high-density liquid transition. Above the liquid-liquid
      critical pressure, the diffusivity crossover occurs at the Widom line, the line
      along which the thermodynamic response functions show maxima. Below the liquid
      liquid critical pressure, the diffusivity crossover occurs when the limit of
      mechanical stability lines are crossed, as indicated by the hysteresis observed
      when going from high to low temperature and vice versa. These findings show that
      the strong connection between dynamics and thermodynamics found in bulk water
      persists in hydrophobic solutions for concentrations from low to moderate,
      indicating that experiments measuring the relaxation time in aqueous solutions
      represent a viable route for solving the open questions in the field of
      supercooled water.

PMID- 23004764
TI  - Dynamical critical exponents for the mean-field Potts glass.
AB  - In this paper we study the critical behavior of the fully connected p-color Potts
      spin glass at the dynamical transition. In the framework of mode coupling theory
      (MCT), the time autocorrelation function displays a two-step relaxation, with two
      exponents governing the approach to the plateau and the exit from it. Exploiting
      a relation between static and equilibrium dynamics which has been recently
      introduced, we are able to compute the critical slowing down exponents at the
      dynamical transition with arbitrary precision and for any value of the number of
      colors p. When available, we compare our exact results with numerical
      simulations. In addition, we present a detailed study of the dynamical transition
      in the large p limit, showing that the system is not equivalent to a random
      energy model.

PMID- 23004765
TI  - Effects of transducer size on impedance spectroscopy measurements.
AB  - The response to an electric field of electrolytic solutions, gels, liquid
      crystals, and other soft materials is described by the drift-diffusion and
      Poisson equations. Existing models, used for the interpretation of experimental
      data, usually consider the system as one dimensional (1D), which is valid only
      for an infinite electrode size. Here we solve numerically the model equations in
      2D, considering a circular electrode with a finite radius, and discuss the limit
      of validity of the 1D approximation.

PMID- 23004766
TI  - Dynamics and energetics of hydrophobically confined water.
AB  - The effects of water confined in regions between self-assembling entities is
      relevant to numerous contexts such as macromolecular association, protein
      folding, protein-ligand association, and nanomaterials self-assembly. Thus
      assessing the impact of confined water, and the ability of current modeling
      techniques to capture the salient features of confined water is important and
      timely. We present molecular dynamics simulation results investigating the effect
      of confined water on qualitative features of potentials of mean force describing
      the free energetics of self-assembly of large planar hydrophobic plates. We
      consider several common explicit water models including the TIP3P, TIP4P, SPC/E,
      TIP4P-FQ, and SWM4-NDP, the latter two being polarizable models. Examination of
      the free energies for filling and unfilling the volume confined between the two
      plates (both in the context of average number of confined water molecules and
      "depth" of occupancy) suggests TIP4P-FQ water molecules generally occupy the
      confined volume at separation distances larger than observed for other models
      under the same conditions. The connection between this tendency of TIP4P-FQ water
      and the lack of a pronounced barrier in the potential of mean force for plate
      plate association in TIP4P-FQ water is explored by artificially, but
      systematically, populating the confined volume with TIP4P-FQ water at low plate
      plate separation distances. When the critical separation distance [denoting the
      crossover from an unoccupied (dry) confined interior to a filled (wet) interior]
      for TIP4P-FQ is reduced by 0.5 A using this approach, a barrier is observed; we
      rationalize this effect based on increased resistant forces introduced by
      confined water molecules at these low separations. We also consider the dynamics
      of water molecules in the confined region between the hydrophobes. We find that
      the TIP4P-FQ water model exhibits nonbulklike dynamics, with enhanced lateral
      diffusion relative to bulk. This is consistent with the reduced intermolecular
      water-water interaction indicated by a decreased molecular dipole moment in the
      interplate region. Analysis of velocity autocorrelation functions and associated
      power spectra indicate that the interplate region for TIP4P-FQ at a plate
      separation of 14.4 A approaches characteristics of the pure water liquid-vapor
      interface. This is in stark contrast to the other water models (including the
      polarizable SWM4-NDP model).

PMID- 23004767
TI  - Shear-transformation-zone theory of viscosity, diffusion, and stretched
      exponential relaxation in amorphous solids.
AB  - The shear-transformation-zone (STZ) theory has been remarkably successful in
      accounting for broadly peaked, frequency-dependent, viscoelastic responses of
      amorphous systems near their glass temperatures T_{g}. This success is based on
      the theory's first-principles prediction of a wide range of internal STZ
      transition rates. Here, I show that the STZ rate distribution causes the
      Newtonian viscosity to be strongly temperature dependent; and I propose that it
      is this temperature dependence, rather than any heterogeneity-induced enhancement
      of diffusion, that is at least in part responsible for Stokes-Einstein violations
      near T_{g}. I also show that stretched-exponential relaxation of density
      fluctuations emerges naturally from the same distribution of STZ transition rates
      that predicts the viscoelastic behavior. To be consistent with observations of
      Fickian diffusion near T_{g}, however, an STZ-based diffusion theory somehow must
      include the cascades of correlated displacement events that are seen in low
      temperature numerical simulations.

PMID- 23004768
TI  - Redefining electrical double layer thickness in narrow confinements: effect of
      solvent polarization.
AB  - In this paper we delineate the consequences of field-dependent solvent
      polarization in the electric double layer (EDL) electrostatic potential
      distribution, and the effective EDL thickness in narrow nanofluidic confinements
      with thick (or overlapping) EDLs. The EDL, formed at the interface between a
      charged substrate and an electrolyte solution, induces a large electric field
      spanning across few nanometer distances from the interface. As a result, a polar
      solvent like water gets polarized, making its relative permittivity a function of
      the EDL electric field. This affects the overall EDL electrostatic potential
      distribution and most importantly, leads to a significant reduction of the
      effective EDL thickness, with the extent of the reduction being dictated by the
      value of field independent EDL thickness, strength of the solvent polarization,
      and the substrate-liquid interfacial electrostatic potential. Such a finding will
      necessitate redefining the classical EDL thickness, which will be of overwhelming
      significance in nanofluidic transport.

PMID- 23004769
TI  - Structure and polarization properties of water: molecular dynamics with a
      nonadditive intermolecular potential.
AB  - The temperature and density dependence of the structure and polarization
      properties of bulk water were systematically investigated using the ab initio
      MCYna potential [Li et al., J. Chem. Phys. 127, 154509 (2007)], which includes
      nonadditive contributions to intermolecular interactions. Molecular dynamics
      simulations were conducted for isochores of 1, 0.8, and 0.6 g/cm^{3} and
      temperatures from 278 to 750 K. Special attention was paid to the structural
      change of water in the range from the normal boiling point to supercritical
      temperatures. At temperatures below the normal boiling temperature, water
      exhibits a tetrahedral structure along the 0.8 and 0.6 g/cm^{3} isochores. A
      significant collapse of the hydrogen bonding network was observed at temperatures
      of 450, 550, and 650 K. The MCYna potential was able to successfully reproduce
      the experimental dielectric constant. The dielectric constant and average dipole
      moments decrease with increasing temperature and decreasing density due to
      weakened polarization. A comparison is also made with SPC-based models.

PMID- 23004770
TI  - Droplet motion in one-component fluids on solid substrates with wettability
      gradients.
AB  - Droplet motion on solid substrates has been widely studied not only because of
      its importance in fundamental research but also because of its promising
      potentials in droplet-based devices developed for various applications in
      chemistry, biology, and industry. In this paper, we investigate the motion of an
      evaporating droplet in one-component fluids on a solid substrate with a
      wettability gradient. As is well known, there are two major difficulties in the
      continuum description of fluid flows and heat fluxes near the contact line of
      droplets on solid substrates, namely, the hydrodynamic (stress) singularity and
      thermal singularity. To model the droplet motion, we use the dynamic van der
      Waals theory [Phys. Rev. E 75, 036304 (2007)] for the hydrodynamic equations in
      the bulk region, supplemented with the boundary conditions at the fluid-solid
      interface. In this continuum hydrodynamic model, various physical processes
      involved in the droplet motion can be taken into account simultaneously, e.g.,
      phase transitions (evaporation or condensation), capillary flows, fluid velocity
      slip, and substrate cooling or heating. Due to the use of the phase field method
      (diffuse interface method), the hydrodynamic and thermal singularities are
      resolved automatically. Furthermore, in the dynamic van der Waals theory, the
      evaporation or condensation rate at the liquid-gas interface is an outcome of the
      calculation rather than a prerequisite as in most of the other models proposed
      for evaporating droplets. Numerical results show that the droplet migrates in the
      direction of increasing wettability on the solid substrates. The migration
      velocity of the droplet is found to be proportional to the wettability gradients
      as predicted by Brochard [Langmuir 5, 432 (1989)]. The proportionality
      coefficient is found to be linearly dependent on the ratio of slip length to
      initial droplet radius. These results indicate that the steady migration of the
      droplets results from the balance between the (conservative) driving force due to
      the wettability gradient and the (dissipative) viscous drag force. In addition,
      we study the motion of droplets on cooled or heated solid substrates with
      wettability gradients. The fast temperature variations from the solid to the
      fluid can be accurately described in the present approach. It is observed that
      accompanying the droplet migration, the contact lines move through phase
      transition and boundary velocity slip with their relative contributions mostly
      determined by the slip length. The results presented in this paper may lead to a
      more complete understanding of the droplet motion driven by wettability gradients
      with a detailed picture of the fluid flows and phase transitions in the vicinity
      of the moving contact line.

PMID- 23004771
TI  - Surface-tension-induced flattening of a nearly plane elastic solid.
AB  - We report direct measurement of surface deformation in soft solids due to their
      surface tension. Gel replicas of poly(dimethysiloxane) masters with rippled
      surfaces are found to have amplitudes that decrease with decreasing gel modulus.
      Surface undulations of a thin elastomeric film are attenuated when it is oxidized
      by brief exposure to oxygen plasma. Surface deformation in both cases is modeled
      successfully as driven by surface tension and resisted by elasticity. Our results
      show that surface tension of soft solids drives significant deformation, and that
      the latter can be used to determine the former.

PMID- 23004772
TI  - Complete wetting of elastically responsive substrates.
AB  - We analyze theoretically complete wetting of a substrate supporting an array of
      parallel, vertical plates which can tilt elastically. The adsorbed liquid tilts
      the plates, inducing clustering, and thus modifies the substrate geometry. In
      turn, this change in geometry alters the wetting properties of the substrate and,
      consequently, the adsorption of liquid. This geometry-wetting feedback loop leads
      to stepped adsorption isotherms with each step corresponding to an abrupt change
      in the substrate geometry. We discuss how this can be used for constructing
      substrates with tunable wetting and adsorption properties.

PMID- 23004773
TI  - Phase behavior of two-component lipid membranes: theory and experiments.
AB  - The structure of the ripple phase of phospholipid membranes remains poorly
      understood in spite of a large number of theoretical studies, with many
      experimentally established structural features of this phase unaccounted for. In
      this article we present a phenomenological theory of phase transitions in single-
      and two-component achiral lipid membranes in terms of two coupled order
      parameters: a scalar order parameter describing lipid chain melting, and a vector
      order parameter describing the tilt of the hydrocarbon chains below the chain
      melting transition. This model reproduces all the salient structural features of
      the ripple phase, providing a unified description of the phase diagram and
      microstructure. In addition, it predicts a variant of this phase that does not
      seem to have been experimentally observed. Using this model we have calculated
      generic phase diagrams of two-component membranes. We have also determined the
      phase diagram of a two-component lipid membrane from x-ray diffraction studies on
      aligned multilayers. This phase diagram is found to be in good agreement with
      that calculated from the model.

PMID- 23004774
TI  - Effect of intralayer inhomogeneity on helical superstructures of liquid crystals.
AB  - A mechanism to form distorted helical structures in ferroelectric liquid crystals
      is presented. It is shown that the deformation of helical interlayer structures
      of thin smectic systems can be considered as a direct consequence of the surface
      induced spatial inhomogeneity in the distribution of the azimuthal molecular
      orientation within smectic layers. The intralayer azimuthal nonuniformity
      occurring in helical phases is argued to generate a local depolarizing electric
      field of the strength varying not only in smectic layers but also between the
      layers. The resulting modulation of the depolarization level in the direction of
      helical axes is shown to lead to a distortion of helices. Using a simple model,
      including the depolarization interaction, it is demonstrated that the degree of
      the helix deformation strongly varies as parameters of the model are changed. It
      is also shown that strong deformations of extremely short helices, found for
      appropriate values of the parameters, reflect nonuniformity of helicoidal
      superstructures of respective smectic subphases in real liquid crystalline
      systems.

PMID- 23004775
TI  - Photoinduced anchoring on a chalcogenide surface.
AB  - We present basic characteristics and a model of photoinduced anchoring of liquid
      crystals (LCs) on a chalcogenide surface. It was found that characteristics of
      the alignment strongly depend on the LC material for the same chalcogenide glass.
      The photoalignment is partially reversible and can be controlled by changing the
      light polarization direction. We propose a model in which the existence of
      dichroic units on the chalcogenide surface and competition between two mechanisms
      of the photoalignment is suggested. The first mechanism is related to the light
      induced anisotropy on the chalcogenide surface and results in an easy orientation
      axes of a LC parallel to the polarization of the incident light. The second
      mechanism is attributed to an energy transfer from the dichroic units after the
      light absorption to the LC molecules adsorbed on the chalcogenide surface. The
      transferred energy causes polarization-sensitive desorption of the LC molecules
      from the chalcogenide surface and the light-induced easy orientation axis of a LC
      perpendicular to the incident light polarization. The competition between these
      mechanisms leads to the observed change of the direction of the easy axis with
      the exposure.

PMID- 23004776
TI  - Complex interplay of nonlinear processes in dielectric elastomers.
AB  - A combination of experiment and theory shows that dielectric elastomers exhibit
      complex interplay of nonlinear processes. Membranes of a dielectric elastomer are
      prepared in various states of prestretches by using rigid clamps and mechanical
      forces. Upon actuation by voltage, some membranes form wrinkles followed by snap
      through instability, others form wrinkles without the snap-through instability,
      and still others fail by local instability without forming wrinkles. Membranes
      surviving these nonlinear processes are found to attain a constant dielectric
      strength, independent of the state of prestretches. Giant voltage-induced stretch
      of 3.6 is attained.

PMID- 23004777
TI  - Structural behavior of a polymer chain inside an attractive sphere.
AB  - We analyze the structural behavior of a single polymer chain inside an attractive
      sphere. Our model is composed of a coarse-grained polymer and an attractive
      sphere potential. By means of extensive multicanonical Monte Carlo simulations,
      it is shown that the system exhibits a rich phase diagram ranging from highly
      ordered compact to extended random coil structures and from desorbed to partially
      or even completely adsorbed conformations. These findings are identified with
      different structural observables.

PMID- 23004778
TI  - Unifying model of driven polymer translocation.
AB  - We present a Brownian dynamics model of driven polymer translocation, in which
      nonequilibrium memory effects arising from tension propagation (TP) along the cis
      side subchain are incorporated as a time-dependent friction. To solve the
      effective friction, we develop a finite chain length TP formalism, based on the
      idea suggested by Sakaue [Phys. Rev. E 76, 021803 (2007)]. We validate the model
      by numerical comparisons with high-accuracy molecular dynamics simulations,
      showing excellent agreement in a wide range of parameters. Our results show that
      the dynamics of driven translocation is dominated by the nonequilibrium TP along
      the cis side subchain. Furthermore, by solving the model for chain lengths up to
      10^{10} monomers, we show that the chain lengths probed by experiments and
      simulations are typically orders of magnitude below the asymptotic limit. This
      explains both the considerable scatter in the observed scaling of translocation
      time with respect to chain length, and some of the shortcomings of present
      theories. Our study shows that for a quantitative theory of polymer
      translocation, explicit consideration of finite chain length effects is required.

PMID- 23004779
TI  - Shape of adsorbed supercoiled plasmids: an equilibrium description.
AB  - Inspired by recent atomic force microscope (AFM) images of plasmids deposited on
      oppositely charged supported lipid bilayers from salt free solution, we propose a
      model for strongly adsorbed supercoiled cyclic stiff polyelectrolytes. We discuss
      how the excess linking number Lk of the deposited cycle is shared between writhe
      Wr and twist Tw at equilibrium and obtain the typical number of self-crossings in
      the deposited cycle as a function of surface charge density. The number of
      crossings at equilibrium is simply determined by the crossing penalty which is a
      local quantity and by the excess linking number. The number of crossings is well
      defined despite versatile plasmid shapes. For moderate numbers of crossings the
      loops are rather small and localized along the primary cycle, as expected from
      entropic loops. In the regime of many crossings, the cycle takes the shape of a
      regular flat ply ruled by local stiffness. The model allows for a
      semiquantitative comparison with the AFM images of deposited plasmids which are
      strongly charged.

PMID- 23004780
TI  - Mode-coupling approach to polymer diffusion in an unentangled melt. I. The effect
      of density fluctuations.
AB  - We quantitatively assess the effect of density fluctuation modes on the dynamics
      of a tagged polymer in an unentangled melt. To this end, we develop a density
      based mode-coupling theory (dMCT) using the Mori-Zwanzig approach and projecting
      the fluctuating force onto pair-density fluctuation modes. The effect of
      dynamical density fluctuations on the center-of-mass (c.m.) dynamics is also
      analyzed based on a perturbative approach and we show that dMCT and perturbation
      techniques yield identical results. The c.m. velocity autocorrelation function
      (c.m. VAF) exhibits a slow power law relaxation in the time range between the
      monomer time t_{1} and the Rouse relaxation time t_{N}. We obtain an analytical
      expression for the c.m. VAF in terms of molecular parameters. In particular, the
      c.m. VAF scales as -N^{-1}t^{-5/4} (where N is the number of monomer units per
      chain) in the relevant time regime. The results are qualitatively accounted for
      by the dynamical correlation hole effect. The predicted -t^{-5/4} dependence of
      the c.m. VAF is supported by data of non-momentum-conserving computer
      simulations. However, the comparison shows that the theory significantly
      underestimates the amplitude of the effect. This issue is discussed and an
      alternative approach is addressed in the second part of this series [Farago et
      al., Phys. Rev. E 85, 051807 (2012), the following paper].

PMID- 23004781
TI  - Mode-coupling approach to polymer diffusion in an unentangled melt. II. The
      effect of viscoelastic hydrodynamic interactions.
AB  - A mode-coupling theory (MCT) version (called hMCT thereafter) of a recently
      presented theory [Farago, Meyer, and Semenov, Phys. Rev. Lett. 107, 178301
      (2011)] is developed to describe the diffusional properties of a tagged polymer
      in a melt. The hMCT accounts for the effect of viscoelastic hydrodynamic
      interactions (VHIs), that is, a physical mechanism distinct from the density
      based MCT (dMCT) described in the first paper of this series. The two versions of
      the MCT yield two different contributions to the asymptotic behavior of the
      center-of-mass velocity autocorrelation function (c.m. VAF). We show that in most
      cases the VHI mechanism is dominant; for long chains and prediffusive times it
      yields a negative tail ?-N^{-1/2}t^{-3/2} for the c.m. VAF. The case of non
      momentum-conserving dynamics (Langevin or Monte Carlo) is discussed as well. It
      generally displays a distinctive behavior with two successive relaxation stages:
      first -N^{-1}t^{-5/4} (as in the dMCT approach), then -N^{-1/2}t^{-3/2}. Both the
      amplitude and the duration of the first t^{-5/4} stage crucially depend on the
      Langevin friction parameter gamma. All results are also relevant for the early
      time regime of entangled melts. These slow relaxations of the c.m. VAF, thus
      account for the anomalous subdiffusive regime of the c.m. mean square
      displacement widely observed in numerical and experimental works.

PMID- 23004782
TI  - Collective dynamics of model microorganisms with chemotactic signaling.
AB  - Various microorganisms use chemotaxis for signaling among individuals-a common
      strategy for communication that is responsible for the formation of
      microcolonies. We model the microorganisms as autochemotactic active random
      walkers and describe them by an appropriate Langevin dynamics. It consists of
      rotational diffusion of the walker's velocity direction and a deterministic
      torque that aligns the velocity direction along the gradient of a self-generated
      chemical field. To account for finite size, each microorganism is treated as a
      soft disk. Its velocity is modified when it overlaps with other walkers according
      to a linear force-velocity relation and a harmonic repulsion force. We analyze
      two-walker collisions by presenting typical trajectories and by determining a
      state diagram that distinguishes between free walker, metastable, and bounded
      cluster states. We mention an analogy to Kramer's escape problem. Finally, we
      investigate relevant properties of many-walker systems and describe
      characteristics of cluster formation in unbounded geometry and in confinement.

PMID- 23004783
TI  - Sensitivity of global network dynamics to local parameters versus motif structure
      in a cortexlike neuronal model.
AB  - In the field of network dynamics it has been suggested that statistical
      information of motifs, small subnetworks, can help in understanding global
      activity of the entire network. We present a counterexample where the relation
      between the stable synchronized activity modes and network connectivity was
      studied using the Hodgkin-Huxley brain dynamics model. Simulations indicate that
      small motifs of three nodes exhibit different synchronization modes depending on
      their local parameters such as delays, synaptic strength, and external drives.
      Thus the activity of a complex network composed of interconnected motifs cannot
      be extracted from the activity mode of each individual motif and is governed by
      local parameters. Finally, we exemplify how local dynamics ultimately enriches
      the ability of a network to generate diverse modes with a given motif structure.

PMID- 23004784
TI  - Extinction in neutrally stable stochastic Lotka-Volterra models.
AB  - Populations of competing biological species exhibit a fascinating interplay
      between the nonlinear dynamics of evolutionary selection forces and random
      fluctuations arising from the stochastic nature of the interactions. The
      processes leading to extinction of species, whose understanding is a key
      component in the study of evolution and biodiversity, are influenced by both of
      these factors. Here, we investigate a class of stochastic population dynamics
      models based on generalized Lotka-Volterra systems. In the case of neutral
      stability of the underlying deterministic model, the impact of intrinsic noise on
      the survival of species is dramatic: It destroys coexistence of interacting
      species on a time scale proportional to the population size. We introduce a new
      method based on stochastic averaging which allows one to understand this
      extinction process quantitatively by reduction to a lower-dimensional effective
      dynamics. This is performed analytically for two highly symmetrical models and
      can be generalized numerically to more complex situations. The extinction
      probability distributions and other quantities of interest we obtain show
      excellent agreement with simulations.

PMID- 23004785
TI  - Reversibility of red blood cell deformation.
AB  - The ability of cells to undergo reversible shape changes is often crucial to
      their survival. For red blood cells (RBCs), irreversible alteration of the cell
      shape and flexibility often causes anemia. Here we show theoretically that RBCs
      may react irreversibly to mechanical perturbations because of tensile stress in
      their cytoskeleton. The transient polymerization of protein fibers inside the
      cell seen in sickle cell anemia or a transient external force can trigger the
      formation of a cytoskeleton-free membrane protrusion of MUm dimensions. The
      complex relaxation kinetics of the cell shape is shown to be responsible for
      selecting the final state once the perturbation is removed, thereby controlling
      the reversibility of the deformation. In some case, tubular protrusion are
      expected to relax via a peculiar "pearling instability."

PMID- 23004786
TI  - Non-Gaussianity in single-particle tracking: use of kurtosis to learn the
      characteristics of a cage-type potential.
AB  - Nonlinear interaction of membrane proteins with cytoskeleton and membrane leads
      to non-Gaussian structure of their displacement probability distribution. We
      propose a statistical analysis technique for learning the characteristics of the
      nonlinear potential from the time dependence of the cumulants of the displacement
      distribution. The efficiency of the approach is demonstrated on the analysis of
      the kurtosis of the displacement distribution of the particle traveling on a
      membrane in a cage-type potential. Results of numerical simulations are supported
      by analytical predictions. We show that the approach allows robust identification
      of some characteristics of the potential for the much lower temporal resolution
      compared with the mean-square displacement analysis and we demonstrate robustness
      to experimental errors in determining the particle positions.

PMID- 23004787
TI  - Curvature sorting of proteins on a cylindrical lipid membrane tether connected to
      a reservoir.
AB  - Membrane curvature of a biological cell is actively involved in various
      fundamental cell biological functions. It has been discovered that membrane
      curvature and binding of peripheral membrane proteins follow a symbiotic
      relationship. The exact mechanism behind this interplay of protein binding and
      membrane curvature has not yet been properly understood. To improve understanding
      of the mechanism, we study curvature sorting of proteins in a model system
      consisting of a tether pulled from a giant unilamellar vesicle using mechanical
      thermodynamic models. The concentration of proteins bound to the membrane changes
      significantly due to curvature. This has also been observed in experiments by
      other researchers. We also find that there is a phase transition based on protein
      concentration and we discuss the coexistence of phases and stability of
      solutions. Furthermore, when sorting is favorable, the increase in protein
      concentration stabilizes the tether in the sense that less pulling force is
      required to maintain the tether. A similar mechanism may be in place, when motor
      proteins pull tethers from donor membranes.

PMID- 23004788
TI  - Modeling ion channel dynamics through reflected stochastic differential
      equations.
AB  - Ion channels are membrane proteins that open and close at random and play a vital
      role in the electrical dynamics of excitable cells. The stochastic nature of the
      conformational changes these proteins undergo can be significant, however current
      stochastic modeling methodologies limit the ability to study such systems.
      Discrete-state Markov chain models are seen as the "gold standard," but are
      computationally intensive, restricting investigation of stochastic effects to the
      single-cell level. Continuous stochastic methods that use stochastic differential
      equations (SDEs) to model the system are more efficient but can lead to
      simulations that have no biological meaning. In this paper we show that modeling
      the behavior of ion channel dynamics by a reflected SDE ensures biologically
      realistic simulations, and we argue that this model follows from the continuous
      approximation of the discrete-state Markov chain model. Open channel and action
      potential statistics from simulations of ion channel dynamics using the reflected
      SDE are compared with those of a discrete-state Markov chain method. Results show
      that the reflected SDE simulations are in good agreement with the discrete-state
      approach. The reflected SDE model therefore provides a computationally efficient
      method to simulate ion channel dynamics while preserving the distributional
      properties of the discrete-state Markov chain model and also ensuring
      biologically realistic solutions. This framework could easily be extended to
      other biochemical reaction networks.

PMID- 23004789
TI  - Spin dephasing in a magnetic dipole field.
AB  - Transverse relaxation by dephasing in an inhomogeneous field is a general
      mechanism in physics, for example, in semiconductor physics, muon spectroscopy,
      or nuclear magnetic resonance. In magnetic resonance imaging the transverse
      relaxation provides information on the properties of several biological tissues.
      Since the dipole field is the most important part of the multipole expansion of
      the local inhomogeneous field, dephasing in a dipole field is highly important in
      relaxation theory. However, there have been no analytical solutions which
      describe the dephasing in a magnetic dipole field. In this work we give a
      complete analytical solution for the dephasing in a magnetic dipole field which
      is valid over the whole dynamic range.

PMID- 23004790
TI  - Organization and evolution of synthetic idiotypic networks.
AB  - We introduce a class of weighted graphs whose properties are meant to mimic the
      topological features of idiotypic networks, namely, the interaction networks
      involving the B core of the immune system. Each node is endowed with a bit string
      representing the idiotypic specificity of the corresponding B cell, and the
      proper distance between any couple of bit strings provides the coupling strength
      between the two nodes. We show that a biased distribution of the entries in bit
      strings can yield fringes in the (weighted) degree distribution, small-world
      features, and scaling laws, in agreement with experimental findings. We also
      investigate the role of aging, thought of as a progressive increase in the degree
      of bias in bit strings, and we show that it can possibly induce mild percolation
      phenomena, which are investigated too.

PMID- 23004792
TI  - Phase lag in epidemics on a network of cities.
AB  - We study the synchronization and phase lag of fluctuations in the number of
      infected individuals in a network of cities between which individuals commute.
      The frequency and amplitude of these oscillations is known to be very well
      captured by the van Kampen system-size expansion, and we use this approximation
      to compute the complex coherence function that describes their correlation. We
      find that, if the infection rate differs from city to city and the coupling
      between them is not too strong, these oscillations are synchronized with a well
      defined phase lag between cities. The analytic description of the effect is shown
      to be in good agreement with the results of stochastic simulations for realistic
      population sizes.

PMID- 23004791
TI  - Extrusion of small vesicles through nanochannels: a model for experiments and
      molecular dynamics simulations.
AB  - We propose a model that predicts the final sizes of lipid bilayer vesicles
      produced by pressure extrusion through nanochannels and we conduct large-scale
      coarse-grained molecular dynamics simulations of the phenomenon. We show that, to
      a first approximation independent of pressure, vesicle size can be predicted by a
      simple geometrical argument that considers an invariable inner vesicle volume
      enclosed by a finitely extensible lipid bilayer. The pressure dependence is then
      incorporated in our model by arguing that the effective channel radius decreases
      with increasing pressure due to a thickening of the lubrication layer between the
      vesicles and the channel wall. We fit our model to the experimental data of Patty
      and Frisken [Biophys. J. 85, 996 (2003)]. We predict that at high pressure,
      vesicle size significantly depends on channel length and, therefore, flow rate.
      The CGMD simulations reproduce the physical principles of the model. They also
      show the build-up of the stress in the vesicle, and typical rupture scenarios as
      the pressure gradient is increased.

PMID- 23004793
TI  - Competition between Na+ and Rb+ in the minor groove of DNA.
AB  - The competition between Na+ and Rb+ ions in the minor groove of a synthetic B-DNA
      dodecamer d (CGCGAATTCGCG) is studied using molecular dynamics simulations as the
      ratio of these two ions changing from 9:1 to 1:9 with the DNA merged into the
      solvent of water molecule at 298 K. When the concentration of Rb+ ions increases,
      from minority to majority, Na+ ions are gradually released from the A tract, and
      the binding sites in the minor groove are occupied by Rb+ ions, extending from
      the A tract to the whole minor groove. Comparing Na+ with Rb+ ions, the
      conformation of the minor groove is influenced strongly by Na+ ions.

PMID- 23004795
TI  - High-energy deformation of filaments with internal structure and localized torque
      induced melting of DNA.
AB  - We develop a continuum elastic approach to examining the bending mechanics of
      semiflexible filaments with a local internal degree of freedom that couples to
      the bending modulus. We apply this model to study the nonlinear mechanics of a
      double-stranded DNA oligomer (shorter than its thermal persistence length) whose
      free ends are linked by a single-stranded DNA chain. This construct, studied by
      H. Qu and G. Zocchi [Europhys. Lett. 94, 18003 (2011)], displays nonlinear strain
      softening associated with the local melting of the double-stranded DNA under
      applied torque and serves as a model system with which to study the nonlinear
      elasticity of DNA under large energy deformations. We show that one can account
      quantitatively for the observed bending mechanics using an augmented wormlike
      chain model, the helix-coil wormlike chain. We also predict that the highly bent
      and partially molten dsDNA should exhibit particularly large end-to-end
      fluctuations associated with the fluctuation of the length of the molten region,
      and propose appropriate experimental tests. We suggest that the augmented
      wormlike chain model discussed here is a useful analytic approach to the
      nonlinear mechanics of DNA or other biopolymer systems.

PMID- 23004794
TI  - Effects of intrinsic stochasticity on delayed reaction-diffusion patterning
      systems.
AB  - Cellular gene expression is a complex process involving many steps, including the
      transcription of DNA and translation of mRNA; hence the synthesis of proteins
      requires a considerable amount of time, from ten minutes to several hours. Since
      diffusion-driven instability has been observed to be sensitive to perturbations
      in kinetic delays, the application of Turing patterning mechanisms to the problem
      of producing spatially heterogeneous differential gene expression has been
      questioned. In deterministic systems a small delay in the reactions can cause a
      large increase in the time it takes a system to pattern. Recently, it has been
      observed that in undelayed systems intrinsic stochasticity can cause pattern
      initiation to occur earlier than in the analogous deterministic simulations. Here
      we are interested in adding both stochasticity and delays to Turing systems in
      order to assess whether stochasticity can reduce the patterning time scale in
      delayed Turing systems. As analytical insights to this problem are difficult to
      attain and often limited in their use, we focus on stochastically simulating
      delayed systems. We consider four different Turing systems and two different
      forms of delay. Our results are mixed and lead to the conclusion that, although
      the sensitivity to delays in the Turing mechanism is not completely removed by
      the addition of intrinsic noise, the effects of the delays are clearly
      ameliorated in certain specific cases.

PMID- 23004796
TI  - Reconstruction of phase maps from the configuration of phase singularities in two
      dimensional manifolds.
AB  - Phase singularity analysis provides a quantitative description of spiral wave
      patterns observed in chemical or biological excitable media. The configuration of
      phase singularities (locations and directions of rotation) is easily derived from
      phase maps in two-dimensional manifolds. The question arises whether one can
      construct a phase map with a given configuration of phase singularities. The
      existence of such a phase map is guaranteed provided that the phase singularity
      configuration satisfies a certain constraint associated with the topology of the
      supporting medium. This paper presents a constructive mathematical approach to
      numerically solve this problem in the plane and on the sphere as well as in more
      general geometries relevant to atrial anatomy including holes and a septal wall.
      This tool can notably be used to create initial conditions with a controllable
      spiral wave configuration for cardiac propagation models and thus help in the
      design of computer experiments in atrial electrophysiology.

PMID- 23004797
TI  - Topology and energy transport in networks of interacting photosynthetic
      complexes.
AB  - We address the role of topology in the energy transport process that occurs in
      networks of photosynthetic complexes. We take inspiration from light-harvesting
      networks present in purple bacteria and simulate an incoherent dissipative energy
      transport process on more general and abstract networks, considering both regular
      structures (Cayley trees and hyperbranched fractals) and randomly generated ones.
      We focus on the the two primary light-harvesting complexes of purple bacteria,
      i.e., the LH1 and LH2, and we use network-theoretical centrality measures in
      order to select different LH1 arrangements. We show that different choices cause
      significant differences in the transport efficiencies, and that for regular
      networks, centrality measures allow us to identify arrangements that ensure
      transport efficiencies which are better than those obtained with a random
      disposition of the complexes. The optimal arrangements strongly depend on the
      dissipative nature of the dynamics and on the topological properties of the
      networks considered, and depending on the latter, they are achieved by using
      global versus local centrality measures. For randomly generated networks, a
      random arrangement of the complexes already provides efficient transport, and
      this suggests the process is strong with respect to limited amount of control in
      the structure design and to the disorder inherent in the construction of randomly
      assembled structures. Finally, we compare the networks considered with the real
      biological networks and find that the latter have in general better performances,
      due to their higher connectivity, but the former with optimal arrangements can
      mimic the real networks' behavior for a specific range of transport parameters.
      These results show that the use of network-theoretical concepts can be crucial
      for the characterization and design of efficient artificial energy transport
      networks.

PMID- 23004798
TI  - Strongly nonlinear waves in capillary electrophoresis.
AB  - In capillary electrophoresis, sample ions migrate along a microcapillary filled
      with a background electrolyte under the influence of an applied electric field.
      If the sample concentration is sufficiently high, the electrical conductivity in
      the sample zone could differ significantly from the background. Under such
      conditions, the local migration velocity of sample ions becomes concentration
      dependent, resulting in a nonlinear wave that exhibits shocklike features. If the
      nonlinearity is weak, the sample concentration profile, under certain simplifying
      assumptions, can be shown to obey Burgers' equation [Ghosal and Chen, Bull. Math.
      Biol. 72, 2047 (2010)], which has an exact analytical solution for arbitrary
      initial condition. In this paper, we use a numerical method to study the problem
      in the more general case where the sample concentration is not small in
      comparison to the concentration of background ions. In the case of low
      concentrations, the numerical results agree with the weakly nonlinear theory
      presented earlier, but at high concentrations, the wave evolves in a way that is
      qualitatively different.

PMID- 23004799
TI  - Macroscopic loop formation in circular DNA denaturation.
AB  - The statistical mechanics of DNA denaturation under fixed linking number is
      qualitatively different from that of unconstrained DNA. Quantitatively different
      melting scenarios are reached from two alternative assumptions, namely, that the
      denatured loops are formed at the expense of (i) overtwist or (ii) supercoils.
      Recent work has shown that the supercoiling mechanism results in a picture
      similar to Bose-Einstein condensation where a macroscopic loop appears at T{c}
      and grows steadily with temperature, while the nature of the denatured phase for
      the overtwisting case has not been studied. By extending an earlier result, we
      show here that a macroscopic loop appears in the overtwisting scenario as well.
      We calculate its size as a function of temperature and show that the fraction of
      the total sum of microscopic loops decreases above T{c}, with a cusp at the
      critical point.

PMID- 23004800
TI  - Cortical free-association dynamics: distinct phases of a latching network.
AB  - A Potts associative memory network has been proposed as a simplified model of
      macroscopic cortical dynamics, in which each Potts unit stands for a patch of
      cortex, which can be activated in one of S local attractor states. The internal
      neuronal dynamics of the patch is not described by the model, rather it is
      subsumed into an effective description in terms of graded Potts units, with
      adaptation effects both specific to each attractor state and generic to the
      patch. If each unit, or patch, receives effective (tensor) connections from C
      other units, the network has been shown to be able to store a large number p of
      global patterns, or network attractors, each with a fraction a of the units
      active, where the critical load p_{c} scales roughly like p_{c}~CS^{2}/aln(1/a)
      (if the patterns are randomly correlated). Interestingly, after retrieving an
      externally cued attractor, the network can continue jumping, or latching, from
      attractor to attractor, driven by adaptation effects. The occurrence and duration
      of latching dynamics is found through simulations to depend critically on the
      strength of local attractor states, expressed in the Potts model by a parameter
      w. Here we describe with simulations and then analytically the boundaries between
      distinct phases of no latching, of transient and sustained latching, deriving a
      phase diagram in the plane w-T, where T parametrizes thermal noise effects.
      Implications for real cortical dynamics are briefly reviewed in the conclusions.

PMID- 23004801
TI  - Models of membrane electrostatics.
AB  - Formulas are derived for the electrostatic potential of a charge in or near a
      membrane modeled as one or more dielectric slabs lying between two semi-infinite
      dielectrics. One can use these formulas in Monte Carlo codes to compute the
      distribution of ions near cell membranes more accurately than by using Poisson
      Boltzmann theory or its linearized version. Here I use them to discuss the
      electric field of a uniformly charged membrane, the image charges of an ion, the
      distribution of salt ions near a charged membrane, the energy of a zwitterion
      near a lipid slab, and the effect of including the phosphate head groups as thin
      layers of high electric permittivity.

PMID- 23004802
TI  - Mean-field descriptions of collective migration with strong adhesion.
AB  - Random walk models based on an exclusion process with contact effects are often
      used to represent collective migration where individual agents are affected by
      agent-to-agent adhesion. Traditional mean-field representations of these
      processes take the form of a nonlinear diffusion equation which, for strong
      adhesion, does not predict the averaged discrete behavior. We propose an
      alternative suite of mean-field representations, showing that collective
      migration with strong adhesion can be accurately represented using a moment
      closure approach.

PMID- 23004803
TI  - Active particles forced by an asymmetric dichotomous angle drive.
AB  - We analyze the dynamics of particles in two dimensions with constant speed and a
      stochastic switching angle dynamics defined by a correlated dichotomous Markov
      process (telegraph noise) plus Gaussian white noise. We study various cases of
      the asymptotic diffusional motion of the particle which is characterized by the
      effective diffusion coefficient. Expressions for this coefficient are derived and
      discussed in dependence on the correlation time and the intensity of the noise.
      The situation with a given mean curvature is of special interest since a
      nonmonotonic behavior of the effective diffusion coefficient as a function of the
      noise intensity and correlation time is found. A time scale matching condition
      for maximal diffusion is formulated.

PMID- 23004804
TI  - Particle velocity distribution in saltation transport.
AB  - We report on wind-tunnel measurements of particle velocity distribution in
      aeolian transport. By performing extended statistics, we show that for saltation
      occurring over an erodible bed the vertical lift-off velocity distributions
      deviate significantly from a Gaussian law and exhibit a long tail accurately
      described by a lognormal law. In contrast, saltation over a rigid bed produces
      Gaussian velocity distributions. These results strongly suggest that the
      deviation from Gaussian distributions is a consequence of the splash process
      which is exclusively present in saltation transport over an erodible bed. We
      further suggest that the non-Gaussian statistics is intimately related to the
      statistical properties of a single splash event which produces ejection of
      particles with lift-off velocities distributed according to a lognormal law. This
      lognormal behavior can be simply inferred from the propagation process of the
      impact energy through the granular bed which can be viewed as the analog of a
      fragmentation process. These findings emphasize the crucial role of the splash
      process in saltation transport.

PMID- 23004805
TI  - Role of hydrogen bonds and molecular structure in relaxation dynamics of pentiol
      isomers.
AB  - Although the presence of hydrogen bonds determines most properties of associated
      materials, their role in relaxation dynamics of liquids remains unclear. Very
      recently Nakanishi and Nozaki [M. Nakanishi and R. Nozaki, Phys. Rev. E 84,
      011503 (2011)] proposed a simplified model for the description of the molecular
      dynamics of H-bonding network and tested its validity for several polyols. The
      authors concluded that relaxation dynamics is controlled mainly by the number of
      hydroxyl groups, whereas the role of molecular architecture can be neglected.
      This conclusion, as demonstrated herein, fails in the case of pentiols. When we
      take into account the role of molecular architecture for development of H-bonded
      structures, it is still possible to satisfactorily describe molecular dynamics in
      polyols with the use of the Nakanishi and Nozaki model.

PMID- 23004806
TI  - Comment on "effect of polydispersity on the ordering transition of adsorbed self
      assembled rigid rods".
AB  - The critical behavior of self-assembled rigid rods on a square lattice was
      recently reinvestigated by Almarza et al. [Phys. Rev. E 82, 061117 (2010)]. Based
      on the Binder cumulants and the value of the critical exponent of the correlation
      length, the authors found that the isotropic-nematic phase transition occurring
      in the system is in the two-dimensional Ising universality class. This conclusion
      contrasts with that of a previous study [Lopez et al., Phys. Rev. E 80, 040105(R)
      (2009)] which indicates that the transition at intermediate density belongs to
      the q=1 Potts universality class. Almarza et al. attributed the discrepancy to
      the use of the density as the control parameter by Lopez et al. The present work
      shows that this suggestion is not sufficient, and that the discrepancy arises
      solely from the use of different statistical ensembles. Finally, the necessity of
      making corrections to the scaling functions in the canonical ensemble is
      discussed.

PMID- 23004808
TI  - Comment on "transient-state fluctuationlike relation for the driving force on a
      biomolecule".
AB  - Two analytically tractable systems, Brownian particles in (i) moving harmonic
      oscillator or (ii) with a time-dependent natural frequency, obey a force
      fluctuation theorem similar to that proposed by Ponmurugan and Vemparala [Phys.
      Rev. E 84, 060101(R) (2011)]. Many of their results can be explained by using the
      former case as a model.

PMID- 23004809
TI  - Dynamic pattern formation and collisions in networks of excitable elements.
AB  - Spatially extended, excitable systems with resting, activated, and refractory
      states, and emergent localized propagating patterns, are widespread in nature.
      Here a unique type of three-state excitable network model is shown to generate
      such dynamic patterns with rich collective dynamics. It is shown that symmetry
      breaking leads to the formation of dynamical patterns, leading to a change from
      local subdiffusive wandering to directed superdiffusive propagation. Furthermore,
      the model yields a rich repertoire of collision dynamics between localized
      propagating patterns and between propagating patterns and the refractory wakes of
      others. This work is particularly motivated by recent experimental studies of
      neural systems that exhibit localized propagating patterns, exemplifying a far
      wider class of excitable systems.

PMID- 23004810
TI  - Dynamic fracture in irregularly structured systems.
AB  - Although commonly used materials are composed of irregular microstructures, most
      existing numerical methods for fracture dynamics are developed via regular
      discretizations. In the present Rapid Communication we investigate the dynamic
      fracture numerically by irregular domain discretizations. To explore the
      relationship between microscopic crack branching and the macroscopic instability
      of fracture dynamics, we simulate detailed diagrams for the crack branching and
      also calculate the crack speeds by varying the parameters of crack-tip cohesion.
      In particular, an equation to describe the relation between the crack speed and
      the fracture energy is proposed based on the simulation results. The present
      results indicate that the irregularities of mesoscopic structure contribute to
      the intrinsic instabilities of dynamic fracture and eventually to the crack
      speed. And the single-crack continuum theory should be at least carefully
      modified to describe the dynamic fracture governed by the complex branching and
      fluctuations.

PMID- 23004811
TI  - Swarming of self-propelled camphor boats.
AB  - When an ensemble of self-propelled camphor boats move in a one-dimensional
      channel, they exhibit a variety of collective behaviors. Under certain
      conditions, the boats tend to cluster together and move in a relatively tight
      formation. This type of behavior, referred to as clustering or swarming here, is
      one of three types recently observed in experiment. Similar clustering behavior
      is also reproduced in simulations based on a simple theoretical model. Here we
      examine this model to determine the clustering mechanism and the conditions under
      which clustering occurs. We also propose a method of quantifying the behavior
      that may be used in future experimental work.

PMID- 23004812
TI  - Electromagnetic oscillations in a driven nonlinear resonator: a description of
      complex nonlinear dynamics.
AB  - Many intriguing properties of driven nonlinear resonators, including the
      appearance of chaos, are very important for understanding the universal features
      of nonlinear dynamical systems and can have great practical significance. We
      consider a cylindrical cavity resonator driven by an alternating voltage and
      filled with a nonlinear nondispersive medium. It is assumed that the medium lacks
      a center of inversion and the dependence of the electric displacement on the
      electric field can be approximated by an exponential function. We show that the
      Maxwell equations are integrated exactly in this case and the field components in
      the cavity are represented in terms of implicit functions of special form. The
      driven electromagnetic oscillations in the cavity are found to display very
      interesting temporal behavior and their Fourier spectra contain singular
      continuous components. This is a demonstration of the existence of a singular
      continuous (fractal) spectrum in an exactly integrable system.

PMID- 23004813
TI  - Initial spreading of low-viscosity drops on partially wetting surfaces.
AB  - Liquid drops start spreading directly after coming into contact with a partially
      wetting substrate. Although this phenomenon involves a three-phase contact line,
      the spreading motion is very fast. We study the initial spreading dynamics of low
      viscosity drops using two complementary methods: molecular dynamics simulations
      and high-speed imaging. We access previously unexplored length and time scales
      and provide a detailed picture on how the initial contact between the liquid drop
      and the solid is established. Both methods unambiguously point toward a spreading
      regime that is independent of wettability, with the contact radius growing as the
      square root of time.

PMID- 23004814
TI  - Electrokinetic instability in microchannels.
AB  - The effect of geometric confinement on electroconvective instability due to
      nonequilibrium electro-osmotic slip at the interface of an electrolytic fluid and
      charge-selective solid is studied. It is shown that the topology of the marginal
      stability curves and the behavior of the critical parameters depend strongly on
      both channel geometry and dimensionless Debye length at low voltages for
      sufficiently deep channels, corresponding to the Rubinstein-Zaltzman instability
      mechanism, but that stability is governed almost entirely by channel depth for
      narrow channels at higher voltages. For shallow channels, it is shown that above
      a transition threshold, determined by both channel depth and Debye length, the
      low-voltage instability is completely suppressed.

PMID- 23004815
TI  - Particle-based model for skiing traffic.
AB  - We develop and investigate a particle-based model for ski slope traffic. Skiers
      are modeled as particles with a mass that are exposed to social and physical
      forces, which define the riding behavior of skiers during their descents on ski
      slopes. We also report position and speed data of 21 skiers recorded with GPS
      equipped cell phones on two ski slopes. A comparison of these data with the
      trajectories resulting from computer simulations of our model shows a good
      correspondence. A study of the relationship among the density, speed, and flow of
      skiers reveals that congestion does not occur even with arrival rates of skiers
      exceeding the maximum ski lift capacity. In a sensitivity analysis, we identify
      the kinetic friction coefficient of skis on snow, the skier mass, the range of
      repelling social forces, and the arrival rate of skiers as the crucial parameters
      influencing the simulation results. Our model allows for the prediction of speed
      zones and skier densities on ski slopes, which is important in the prevention of
      skiing accidents.

PMID- 23004816
TI  - Bidirectional sorting of flocking particles in the presence of asymmetric
      barriers.
AB  - We demonstrate numerically bidirectional sorting of flocking particles
      interacting with an array of V-shaped asymmetric barriers. Each particle aligns
      with the average swimming direction of its neighbors according to the Vicsek
      model and experiences additional steric interactions as well as repulsion from
      the fixed barriers. We show that particles preferentially localize to one side of
      the barrier array over time and that the direction of this rectification can be
      reversed by adjusting the particle-particle exclusion radius or the noise term in
      the equations of motion. These results provide a conceptual basis for isolation
      and sorting of single-cell and multicellular organisms that move collectively
      according to flocking-type interaction rules.

PMID- 23004817
TI  - Dynamical model for competing opinions.
AB  - We propose an opinion model based on agents located at the vertices of a regular
      lattice. Each agent has an independent opinion (among an arbitrary, but fixed,
      number of choices) and its own degree of conviction. The latter changes every
      time two agents which have different opinions interact with each other. The
      dynamics leads to size distributions of clusters (made up of agents which have
      the same opinion and are located at contiguous spatial positions) which follow a
      power law, as long as the range of the interaction between the agents is not too
      short; i.e., the system self-organizes into a critical state. Short range
      interactions lead to an exponential cutoff in the size distribution and to
      spatial correlations which cause agents which have the same opinion to be closely
      grouped. When the diversity of opinions is restricted to two, a nonconsensus
      dynamic is observed, with unequal population fractions, whereas consensus is
      reached if the agents are also allowed to interact with those located far from
      them. The individual agents' convictions, the preestablished interaction range,
      and the locality of the interaction between a pair of agents (their neighborhood
      has no effect on the interaction) are the main characteristics which distinguish
      our model from previous ones.

PMID- 23004818
TI  - Directionally asymmetric self-assembly of cadmium sulfide nanotubes using porous
      alumina nanoreactors: need for chemohydrodynamic instability at the nanoscale.
AB  - We explore nanoscale hydrodynamical effects on synthesis and self-assembly of
      cadmium sulfide nanotubes oriented along one direction. These nanotubes are
      synthesized by horizontal capillary flow of two different chemical reagents from
      opposite directions through nanochannels of porous anodic alumina which are used
      primarily as nanoreactors. We show that uneven flow of different chemical
      precursors is responsible for directionally asymmetric growth of these nanotubes.
      On the basis of structural observations using scanning electron microscopy, we
      argue that chemohydrodynamic convective interfacial instability of multicomponent
      liquid-liquid reactive interface is necessary for sustained nucleation of these
      CdS nanotubes at the edges of these porous nanochannels over several hours.
      However, our estimates clearly suggest that classical hydrodynamics cannot
      account for the occurrence of such instabilities at these small length scales.
      Therefore, we present a case which necessitates further investigation and
      understanding of chemohydrodynamic fluid flow through nanoconfined channels in
      order to explain the occurrence of such interfacial instabilities at nanometer
      length scales.

PMID- 23004819
TI  - Evaluation of attractors and basins of asynchronous random Boolean networks.
AB  - We present an algebraic approach for determining the attractors and their basins
      of random Boolean networks under an asynchronous stochastic update based on the
      recently developed matrix semitensor product theory, which allows for converting
      the logical dynamics of a Boolean network into a standard iterative dynamics. In
      this setting, all attractors and basins are specified by the network transition
      matrices. We then devise procedures that can find all attractors and their basins
      exactly. We also discuss the issue of overlapping basins in asynchronous random
      Boolean networks, and we propose methods to compute the weight of each attractor
      and the basin entropy of the systems.

PMID- 23004820
TI  - Epidemic spreading in weighted networks: an edge-based mean-field solution.
AB  - Weight distribution greatly impacts the epidemic spreading taking place on top of
      networks. This paper presents a study of a susceptible-infected-susceptible model
      on regular random networks with different kinds of weight distributions.
      Simulation results show that the more homogeneous weight distribution leads to
      higher epidemic prevalence, which, unfortunately, could not be captured by the
      traditional mean-field approximation. This paper gives an edge-based mean-field
      solution for general weight distribution, which can quantitatively reproduce the
      simulation results. This method could be applied to characterize the
      nonequilibrium steady states of dynamical processes on weighted networks.

PMID- 23004821
TI  - Ranking and clustering of nodes in networks with smart teleportation.
AB  - Random teleportation is a necessary evil for ranking and clustering directed
      networks based on random walks. Teleportation enables ergodic solutions, but the
      solutions must necessarily depend on the exact implementation and parametrization
      of the teleportation. For example, in the commonly used PageRank algorithm, the
      teleportation rate must trade off a heavily biased solution with a uniform
      solution. Here we show that teleportation to links rather than nodes enables a
      much smoother trade-off and effectively more robust results. We also show that,
      by not recording the teleportation steps of the random walker, we can further
      reduce the effect of teleportation with dramatic effects on clustering.

PMID- 23004822
TI  - Quantifying reflexivity in financial markets: toward a prediction of flash
      crashes.
AB  - We introduce a measure of activity of financial markets that provides a direct
      access to their level of endogeneity. This measure quantifies how much of price
      changes is due to endogenous feedback processes, as opposed to exogenous news.
      For this, we calibrate the self-excited conditional Poisson Hawkes model, which
      combines in a natural and parsimonious way exogenous influences with self-excited
      dynamics, to the E-mini S&P 500 futures contracts traded in the Chicago
      Mercantile Exchange from 1998 to 2010. We find that the level of endogeneity has
      increased significantly from 1998 to 2010, with only 70% in 1998 to less than 30%
      since 2007 of the price changes resulting from some revealed exogenous
      information. Analogous to nuclear plant safety measures concerned with avoiding
      "criticality," our measure provides a direct quantification of the distance of
      the financial market from a critical state defined precisely as the limit of
      diverging trading activity in the absence of any external driving.

PMID- 23004823
TI  - Community structure and scale-free collections of Erdos-Renyi graphs.
AB  - Community structure plays a significant role in the analysis of social networks
      and similar graphs, yet this structure is little understood and not well captured
      by most models. We formally define a community to be a subgraph that is
      internally highly connected and has no deeper substructure. We use tools of
      combinatorics to show that any such community must contain a dense Erdos-Renyi
      (ER) subgraph. Based on mathematical arguments, we hypothesize that any graph
      with a heavy-tailed degree distribution and community structure must contain a
      scale-free collection of dense ER subgraphs. These theoretical observations
      corroborate well with empirical evidence. From this, we propose the Block Two
      Level Erdos-Renyi (BTER) model, and demonstrate that it accurately captures the
      observable properties of many real-world social networks.

PMID- 23004824
TI  - Common community structure in time-varying networks.
AB  - In this report we introduce the concept of common community structure in time
      varying networks. We propose a novel optimization algorithm to rapidly detect
      common community structure in such networks. Both theoretical and numerical
      results show that the proposed method not only can resolve detailed common
      communities, but also can effectively identify the dynamical phenomena in time
      varying networks.

PMID- 23004825
TI  - Second-order mean-field susceptible-infected-susceptible epidemic threshold.
AB  - Given the adjacency matrix A of a network, we present a second-order mean-field
      expansion that improves on the first-order N-intertwined susceptible-infected
      susceptible (SIS) epidemic model. Unexpectedly, we found that, in contrast to
      first-order, second-order mean-field theory is not always possible: the network
      size N should be large enough. Under the assumption of large N, we show that the
      crucial and characterizing quantity, the SIS epidemic threshold tau(c), obeys an
      eigenvalue equation, more complex than the one in the first-order N-intertwined
      model. However, the resulting epidemic threshold is more accurate: tau(c)((2)) =
      tau(c)((1)) + O(tau(c)((1))/N), where the first-order epidemic threshold is
      tau(c)((1)) = 1/lambda(1)(A) and where lambda(1)(A) is the spectral radius of the
      adjacency matrix A.

PMID- 23004826
TI  - Finding missing edges in networks based on their community structure.
AB  - Many edge prediction methods have been proposed, based on various local or global
      properties of the structure of an incomplete network. Community structure is
      another significant feature of networks: Vertices in a community are more densely
      connected than average. It is often true that vertices in the same community have
      "similar" properties, which suggests that missing edges are more likely to be
      found within communities than elsewhere. We use this insight to propose a
      strategy for edge prediction that combines existing edge prediction methods with
      community detection. We show that this method gives better prediction accuracy
      than existing edge prediction methods alone.

PMID- 23004827
TI  - Statistical mechanics of the international trade network.
AB  - Analyzing real data on international trade covering the time interval 1950-2000,
      we show that in each year over the analyzed period the network is a typical
      representative of the ensemble of maximally random weighted networks, whose
      directed connections (bilateral trade volumes) are only characterized by the
      product of the trading countries' GDPs. It means that time evolution of this
      network may be considered as a continuous sequence of equilibrium states, i.e., a
      quasistatic process. This, in turn, allows one to apply the linear response
      theory to make (and also verify) simple predictions about the network. In
      particular, we show that bilateral trade fulfills a fluctuation-response theorem,
      which states that the average relative change in imports (exports) between two
      countries is a sum of the relative changes in their GDPs. Yearly changes in trade
      volumes prove that the theorem is valid.

PMID- 23004828
TI  - Stochastic synchronization in blinking networks of chaotic maps.
AB  - In this paper we analyze stochastic synchronization of coupled chaotic maps over
      blinking networks composed of a pristine static network and stochastic on-off
      couplings between any pair of nodes. We focus on mean square linear stability of
      the synchronized state by analyzing the time evolution of the second moment of
      the variation transverse to the synchronization manifold. By projecting the
      variational equations on the eigenvectors of a higher order state matrix
      describing this variational dynamics, we establish a necessary and sufficient
      condition for stochastic synchronization based on the largest Lyapunov exponent
      of the map and the spectral radius of such matrix. This condition is further
      simplified by computing closed-form results for the spectral properties of the
      moments of the graph Laplacian associated to the intermittent coupling and using
      classical eigenvalue bounds. We illustrate the main results through simulations
      on synchronization of chaotic Henon maps.

PMID- 23004829
TI  - Random walks on temporal networks.
AB  - Many natural and artificial networks evolve in time. Nodes and connections appear
      and disappear at various time scales, and their dynamics has profound
      consequences for any processes in which they are involved. The first empirical
      analysis of the temporal patterns characterizing dynamic networks are still
      recent, so that many questions remain open. Here, we study how random walks, as a
      paradigm of dynamical processes, unfold on temporally evolving networks. To this
      aim, we use empirical dynamical networks of contacts between individuals, and
      characterize the fundamental quantities that impact any general process taking
      place upon them. Furthermore, we introduce different randomizing strategies that
      allow us to single out the role of the different properties of the empirical
      networks. We show that the random walk exploration is slower on temporal networks
      than it is on the aggregate projected network, even when the time is properly
      rescaled. In particular, we point out that a fundamental role is played by the
      temporal correlations between consecutive contacts present in the data. Finally,
      we address the consequences of the intrinsically limited duration of many real
      world dynamical networks. Considering the fundamental prototypical role of the
      random walk process, we believe that these results could help to shed light on
      the behavior of more complex dynamics on temporally evolving networks.

PMID- 23004830
TI  - Information spreading and development of cultural centers.
AB  - The historical interplay between societies is governed by many factors, including
      in particular the spreading of languages, religion, and other symbolic traits.
      Cultural development, in turn, is coupled to the emergence and maintenance of
      information spreading. Strong centralized cultures exist due to attention from
      their members, whose faithfulness in turn relies on the supply of information.
      Here we discuss a culture evolution model on a planar geometry that takes into
      account aspects of the feedback between information spreading and its
      maintenance. Features of the model are highlighted by comparing it to cultural
      spreading in ancient and medieval Europe, where it suggests in particular that
      long-lived centers should be located in geographically remote regions.

PMID- 23004831
TI  - Evolution of global cooperation driven by risks.
AB  - Globalization facilitates our communication with each other, while it magnifies
      problems such as overharvesting of natural resources and human-induced climate
      change. Thus people all over the world are involved in a global social dilemma
      which calls for worldwide cooperation to reduce the risks of these extreme events
      and disasters. A collective target (threshold) is required to prevent such
      events. Everyone may lose their wealth once their total individual contributions
      fail to reach the threshold. To this end, we establish a model of threshold
      public goods games in a group-structured population and investigate its
      evolutionary process. We study multilevel public goods games with defectors,
      local cooperators, and global cooperators and are primarily concerned with how
      the global cooperative behavior evolves. We find that, compared with the standard
      public goods games, the strategy of global cooperation accounts for a bigger
      proportion in the stationary distribution of threshold public goods games. On the
      other hand, the fixation time of the global cooperation strategy is greatly
      shortened with increase of the probability of disaster striking. Therefore,
      global risks induced by the threshold can effectively promote global cooperation
      in environmental investment and the reduction of greenhouse gas emissions.

PMID- 23004832
TI  - Foreign exchange market data analysis reveals statistical features that predict
      price movement acceleration.
AB  - Increasingly accessible financial data allow researchers to infer market-dynamics
      based laws and to propose models that are able to reproduce them. In recent
      years, several stylized facts have been uncovered. Here we perform an extensive
      analysis of foreign exchange data that leads to the unveiling of a statistical
      financial law. First, our findings show that, on average, volatility increases
      more when the price exceeds the highest (or lowest) value, i.e., breaks the
      resistance line. We call this the breaking-acceleration effect. Second, our
      results show that the probability P(T) to break the resistance line in the past
      time T follows power law in both real data and theoretically simulated data.
      However, the probability calculated using real data is rather lower than the one
      obtained using a traditional Black-Scholes (BS) model. Taken together, the
      present analysis characterizes a different stylized fact of financial markets and
      shows that the market exceeds a past (historical) extreme price fewer times than
      expected by the BS model (the resistance effect). However, when the market does,
      we predict that the average volatility at that time point will be much higher.
      These findings indicate that any Markovian model does not faithfully capture the
      market dynamics.

PMID- 23004833
TI  - Subgraph fluctuations in random graphs.
AB  - The pattern of over- and under-representations of three-node subgraphs has become
      a standard method of characterizing complex networks and evaluating how this
      intermediate level of organization contributes to network function. Understanding
      statistical properties of subgraph counts in random graphs, their fluctuations,
      and their interdependences with other topological attributes is an important
      prerequisite for such investigations. Here we introduce a formalism for
      predicting subgraph fluctuations induced by perturbations of unidirectional and
      bidirectional edge densities. On this basis we predict the over- and under
      representation of subgraphs arising from a density mismatch between a network and
      the corresponding pool of randomized graphs serving as a null model. Such
      mismatches occur, for example, in modular and hierarchical graphs.

PMID- 23004834
TI  - Extreme events and event size fluctuations in biased random walks on networks.
AB  - Random walk on discrete lattice models is important to understand various types
      of transport processes. The extreme events, defined as exceedences of the flux of
      walkers above a prescribed threshold, have been studied recently in the context
      of complex networks. This was motivated by the occurrence of rare events such as
      traffic jams, floods, and power blackouts which take place on networks. In this
      work, we study extreme events in a generalized random walk model in which the
      walk is preferentially biased by the network topology. The walkers preferentially
      choose to hop toward the hubs or small degree nodes. In this setting, we show
      that extremely large fluctuations in event sizes are possible on small degree
      nodes when the walkers are biased toward the hubs. In particular, we obtain the
      distribution of event sizes on the network. Further, the probability for the
      occurrence of extreme events on any node in the network depends on its
      "generalized strength," a measure of the ability of a node to attract walkers.
      The generalized strength is a function of the degree of the node and that of its
      nearest neighbors. We obtain analytical and simulation results for the
      probability of occurrence of extreme events on the nodes of a network using a
      generalized random walk model. The result reveals that the nodes with a larger
      value of generalized strength, on average, display lower probability for the
      occurrence of extreme events compared to the nodes with lower values of
      generalized strength.

PMID- 23004835
TI  - Structure of S-shaped growth in innovation diffusion.
AB  - A basic question on innovation diffusion is why the growth curve of the adopter
      population in a large society is often S shaped. From macroscopic, microscopic,
      and mesoscopic viewpoints, the growth of the adopter population is observed as
      the growth curve, individual adoptions, and differences among individual
      adoptions, respectively. The S shape can be explained if an empirical model of
      the growth curve can be deduced from models of microscopic and mesoscopic
      structures. However, even the structure of growth curve has not been revealed yet
      because long-term extrapolations by proposed models of S-shaped curves are
      unstable and it has been very difficult to predict the long-term growth and final
      adopter population. This paper studies the S-shaped growth from the viewpoint of
      social regularities. Simple methods to analyze power laws enable us to extract
      the structure of the growth curve directly from the growth data of recent basic
      telecommunication services. This empirical model of growth curve is singular at
      the inflection point and a logarithmic function of time after this point, which
      explains the unstable extrapolations obtained using previously proposed models
      and the difficulty in predicting the final adopter population. Because the
      empirical S curve can be expressed in terms of two power laws of the regularity
      found in social performances of individuals, we propose the hypothesis that the S
      shape represents the heterogeneity of the adopter population, and the
      heterogeneity parameter is distributed under the regularity in social
      performances of individuals. This hypothesis is so powerful as to yield models of
      microscopic and mesoscopic structures. In the microscopic model, each potential
      adopter adopts the innovation when the information accumulated by the learning
      about the innovation exceeds a threshold. The accumulation rate of information is
      heterogeneous among the adopter population, whereas the threshold is a constant,
      which is the opposite of previously proposed models. In the mesoscopic model,
      flows of innovation information incoming to individuals are organized as
      dimorphic and partially clustered. These microscopic and mesoscopic models yield
      the empirical model of the S curve and explain the S shape as representing the
      regularities of information flows generated through a social self-organization.
      To demonstrate the validity and importance of the hypothesis, the models of three
      level structures are applied to reveal the mechanism determining and
      differentiating diffusion speeds. The empirical model of S curves implies that
      the coefficient of variation of the flow rates determines the diffusion speed for
      later adopters. Based on this property, a model describing the inside of
      information flow clusters can be given, which provides a formula interconnecting
      the diffusion speed, cluster populations, and a network topological parameter of
      the flow clusters. For two recent basic telecommunication services in Japan, the
      formula represents the variety of speeds in different areas and enables us to
      explain speed gaps between urban and rural areas and between the two services.
      Furthermore, the formula provides a method to estimate the final adopter
      population.

PMID- 23004836
TI  - Entropy of stochastic blockmodel ensembles.
AB  - Stochastic blockmodels are generative network models where the vertices are
      separated into discrete groups, and the probability of an edge existing between
      two vertices is determined solely by their group membership. In this paper, we
      derive expressions for the entropy of stochastic blockmodel ensembles. We
      consider several ensemble variants, including the traditional model as well as
      the newly introduced degree-corrected version [Karrer et al., Phys. Rev. E 83,
      016107 (2011)], which imposes a degree sequence on the vertices, in addition to
      the block structure. The imposed degree sequence is implemented both as "soft"
      constraints, where only the expected degrees are imposed, and as "hard"
      constraints, where they are required to be the same on all samples of the
      ensemble. We also consider generalizations to multigraphs and directed graphs. We
      illustrate one of many applications of this measure by directly deriving a log
      likelihood function from the entropy expression, and using it to infer latent
      block structure in observed data. Due to the general nature of the ensembles
      considered, the method works well for ensembles with intrinsic degree
      correlations (i.e., with entropic origin) as well as extrinsic degree
      correlations, which go beyond the block structure.

PMID- 23004837
TI  - Ghost resonance in the chaotic Chua's circuit.
AB  - We experimentally investigate the ghost resonance phenomenon in the electronic
      circuit of Chua operating in the chaotic regime. The circuit can be stimulated to
      jump between two single-scroll attractors by an external periodic signal with an
      amplitude above an intrinsic threshold. For subthreshold signals, jumps between
      the chaotic attractors can be promoted by a superposed white noise. We show that
      the circuit output can exhibit a well-defined ghost resonance signature, i.e., a
      resonance on a frequency that is absent in a multicomponent input signal, when
      the amplitudes of the input components are properly related. Further, we show
      that ghost resonance can be induced by the Chua's circuit's own chaotic dynamics
      when it is driven by a suprathreshold multicomponent signal without the need of
      an external noise source.

PMID- 23004838
TI  - Improvements to surrogate data methods for nonstationary time series.
AB  - The method of surrogate data has been extensively applied to hypothesis testing
      of system linearity, when only one realization of the system, a time series, is
      known. Normally, surrogate data should preserve the linear stochastic structure
      and the amplitude distribution of the original series. Classical surrogate data
      methods (such as random permutation, amplitude adjusted Fourier transform, or
      iterative amplitude adjusted Fourier transform) are successful at preserving one
      or both of these features in stationary cases. However, they always produce
      stationary surrogates, hence existing nonstationarity could be interpreted as
      dynamic nonlinearity. Certain modifications have been proposed that additionally
      preserve some nonstationarity, at the expense of reproducing a great deal of
      nonlinearity. However, even those methods generally fail to preserve the trend
      (i.e., global nonstationarity in the mean) of the original series. This is the
      case of time series with unit roots in their autoregressive structure.
      Additionally, those methods, based on Fourier transform, either need first and
      last values in the original series to match, or they need to select a piece of
      the original series with matching ends. These conditions are often inapplicable
      and the resulting surrogates are adversely affected by the well-known artefact
      problem. In this study, we propose a simple technique that, applied within
      existing Fourier-transform-based methods, generates surrogate data that jointly
      preserve the aforementioned characteristics of the original series, including
      (even strong) trends. Moreover, our technique avoids the negative effects of end
      mismatch. Several artificial and real, stationary and nonstationary, linear and
      nonlinear time series are examined, in order to demonstrate the advantages of the
      methods. Corresponding surrogate data are produced with the classical and with
      the proposed methods, and the results are compared.

PMID- 23004839
TI  - Trace formula for chaotic dielectric resonators tested with microwave
      experiments.
AB  - We measured the resonance spectra of two stadium-shaped dielectric microwave
      resonators and tested a semiclassical trace formula for chaotic dielectric
      resonators proposed by Bogomolny et al. [Phys. Rev. E 78, 056202 (2008)]. We
      found good qualitative agreement between the experimental data and the
      predictions of the trace formula. Deviations could be attributed to missing
      resonances in the measured spectra in accordance with previous experiments [Phys.
      Rev. E 81, 066215 (2010)]. The investigation of the numerical length spectrum
      showed good qualitative and reasonable quantitative agreement with the trace
      formula. It demonstrated, however, the need for higher-order corrections of the
      trace formula. The application of a curvature correction to the Fresnel
      reflection coefficients entering the trace formula yielded better agreement, but
      deviations remained, indicating the necessity of further investigations.

PMID- 23004840
TI  - On-off intermittency in an optically injected semiconductor laser.
AB  - We report on the observation of on-off intermittency in an optically injected
      dual-mode semiconductor laser. It is shown that quasi-single-mode chaotic
      dynamics of the injected mode are accompanied by intermittent and irregular
      bursts of the intensity of the uninjected mode. We define a threshold intensity
      of the uninjected mode to distinguish laminar and bursting states of the system.
      For small values of the threshold parameter we observe excellent agreement with
      the predictions of theory for the distribution of the laminar phase durations.
      For larger values of the threshold parameter, a gap appears in the distribution
      of laminar phase durations. Numerical simulations demonstrate that this gap is a
      consequence of the fact that in this case the on states of the system define
      large intensity spikes, which can belong either to the same or to distinct bursts
      away from the single-mode manifold.

PMID- 23004841
TI  - Characterizing topological transitions in a Turing-pattern-forming reaction
      diffusion system.
AB  - Turing structures appear naturally and they are demonstrated under different
      spatial configurations such as stripes and spots as well as mixed states. The
      traditional tool to characterize these patterns is the Fourier transformation,
      which accounts for the spatial wavelength, but it fails to discriminate among
      different spatial configurations or mixed states. In this paper, we propose a
      parameter that clearly differentiates the different spatial configurations. As an
      application, we considered the transitions induced by an external forcing in a
      reaction-diffusion system although the results are straightforwardly extended to
      different problems with similar topologies. The method was also successfully
      tested on a temporally evolving pattern.

PMID- 23004842
TI  - Design of oscillator networks with enhanced synchronization tolerance against
      noise.
AB  - Can synchronization properties of a network of identical oscillators in the
      presence of noise be improved through appropriate rewiring of its connections?
      What are the optimal network architectures for a given total number of
      connections? We address these questions by running the optimization process,
      using the stochastic Markov Chain Monte Carlo method with replica exchange, to
      design networks of phase oscillators with increased tolerance against noise. As
      we find, the synchronization of a network, characterized by the Kuramoto order
      parameter, can be increased up to 40%, as compared to that of the randomly
      generated networks, when the optimization is applied. Large ensembles of
      optimized networks are obtained, and their statistical properties are
      investigated.

PMID- 23004843
TI  - Persistent fluctuations in synchronization rate in globally coupled oscillators
      with periodic external forcing.
AB  - A system of phase oscillators with repulsive global coupling and periodic
      external forcing undergoing asynchronous rotation is considered. The
      synchronization rate of the system can exhibit persistent fluctuations depending
      on parameters and initial phase distributions, and the amplitude of the
      fluctuations scales with the system size for uniformly random initial phase
      distributions. Using the Watanabe-Strogatz transformation that reduces the
      original system to low-dimensional macroscopic equations, we show that the
      fluctuations are collective dynamics of the system corresponding to low
      dimensional trajectories of the reduced equations. It is argued that the
      amplitude of the fluctuations is determined by the inhomogeneity of the initial
      phase distribution, resulting in system-size scaling for the random case.

PMID- 23004844
TI  - Phase response theory extended to nonoscillatory network components.
AB  - New tools for analysis of oscillatory networks using phase response theory (PRT)
      under the assumption of pulsatile coupling have been developed steadily since the
      1980s, but none have yet allowed for analysis of mixed systems containing
      nonoscillatory elements. This caveat has excluded the application of PRT to most
      real systems, which are often mixed. We show that a recently developed tool, the
      functional phase resetting curve (fPRC), provides a serendipitous benefit: it
      allows incorporation of nonoscillatory elements into systems of oscillators where
      PRT can be applied. We validate this method in a model system of neural
      oscillators and a biological system, the pyloric network of crustacean decapods.

PMID- 23004845
TI  - Spectral and correlation properties of rings of delay-coupled elements: comparing
      linear and nonlinear systems.
AB  - The dynamical properties of delay-coupled systems are currently of great
      interest. So far the analysis has concentrated primarily on identical
      synchronization properties. Here we study the dynamics of rings of delay-coupled
      nodes, a topology that cannot show identical synchronization, and compare its
      properties to those of linear stochastic maps. We find that, in the long delay
      limit, the correlation functions and spectra of delay-coupled rings of nonlinear
      systems obey the same scaling laws as linear systems, indicating that important
      properties of the emerging solution result from network topology.

PMID- 23004846
TI  - Mean-field behavior in coupled oscillators with attractive and repulsive
      interactions.
AB  - We consider a variant of the Kuramoto model of coupled oscillators in which both
      attractive and repulsive pairwise interactions are allowed. The sign of the
      coupling is assumed to be a characteristic of a given oscillator. Specifically,
      some oscillators repel all the others, thus favoring an antiphase relationship
      with them. Other oscillators attract all the others, thus favoring an in-phase
      relationship. The Ott-Antonsen ansatz is used to derive the exact low-dimensional
      dynamics governing the system's long-term macroscopic behavior. The resulting
      analytical predictions agree with simulations of the full system. We explore the
      effects of changing various parameters, such as the width of the distribution of
      natural frequencies and the relative strengths and proportions of the positive
      and negative interactions. For the particular model studied here we find,
      unexpectedly, that the mixed interactions produce no new effects. The system
      exhibits conventional mean-field behavior and displays a second-order phase
      transition like that found in the original Kuramoto model. In contrast to our
      recent study of a different model with mixed interactions [Phys. Rev. Lett. 106,
      054102 (2011)], the pi state and traveling-wave state do not appear for the
      coupling type considered here.

PMID- 23004847
TI  - Effects of spatial frequency distributions on amplitude death in an array of
      coupled Landau-Stuart oscillators.
AB  - The influences of spatial frequency distributions on complete amplitude death are
      explored by studying an array of diffusively coupled oscillators. We found that
      with all possible sets of spatial frequency distributions, the two critical
      coupling strengths epsilon(c1) (lower-bounded value) and epsilon(c2) (upper
      bounded value) needed to get complete amplitude death exhibit a universal power
      law and a log-normal distribution respectively, which has long tails in both
      cases. This is significant for dynamics control, since large variations of
      epsilon(c1) and epsilon(c2) are possible for some spatial arrangements. Moreover,
      we explore optimal spatial distributions with the smallest (largest) epsilon(c1)
      or epsilon(c2).

PMID- 23004848
TI  - Scaling properties of discontinuous maps.
AB  - We study the scaling properties of discontinuous maps by analyzing the average
      value of the squared action variable I(2). We focus our study on two dynamical
      regimes separated by the critical value K(c) of the control parameter K: the slow
      diffusion (K < K(c)) and the quasilinear diffusion (K > K(c)) regimes. We found
      that the scaling of I(2) for discontinuous maps when K ? K(c) and K ? K(c) obeys
      the same scaling laws, in the appropriate limits, as Chirikov's standard map in
      the regimes of weak and strong nonlinearity, respectively. However, due to the
      absence of Kolmogorov-Arnold-Moser tori, we observed in both regimes that I(2) ?
      nK(beta) for n ? 1 (n being the nth iteration of the map) with beta ~ 5/2 when K
      ? K(c) and beta ~ 2 for K ? K(c).

PMID- 23004849
TI  - Quasiattractors in coupled maps and coupled dielectric cavities.
AB  - We study the origin of attracting phenomena in the ray dynamics of coupled
      optical microcavities. To this end we investigate a combined map that is composed
      of standard and linear map, and a selection rule that defines when which map has
      to be used. We find that this system shows attracting dynamics, leading exactly
      to a quasiattractor, due to collapse of phase space. For coupled dielectric
      disks, we derive the corresponding mapping based on a ray model with
      deterministic selection rule and study the quasiattractor obtained from it. We
      also discuss a generalized Poincare surface of section at dielectric interfaces.

PMID- 23004850
TI  - Bifurcation threshold of the delayed van der Pol oscillator under stochastic
      modulation.
AB  - We obtain the location of the Hopf bifurcation threshold for a modified van der
      Pol oscillator, parametrically driven by a stochastic source and including
      delayed feedback in both position and velocity. We introduce a multiple scale
      expansion near threshold, and we solve the resulting Fokker-Planck equation
      associated with the evolution at the slowest time scale. The analytical results
      are compared with a direct numerical integration of the model equation. Delay
      modifies the Hopf frequency at threshold and leads to a stochastic bifurcation
      that is shifted relative to the deterministic limit by an amount that depends on
      the delay time, the amplitude of the feedback terms, and the intensity of the
      noise. Interestingly, stochasticity generally increases the region of stability
      of the limit cycle.

PMID- 23004851
TI  - Statistical modeling approach for detecting generalized synchronization.
AB  - Detecting nonlinear correlations between time series presents a hard problem for
      data analysis. We present a generative statistical modeling method for detecting
      nonlinear generalized synchronization. Truncated Volterra series are used to
      approximate functional interactions. The Volterra kernels are modeled as linear
      combinations of basis splines, whose coefficients are estimated via l(1) and l(2)
      regularized maximum likelihood regression. The regularization manages the high
      number of kernel coefficients and allows feature selection strategies yielding
      sparse models. The method's performance is evaluated on different coupled chaotic
      systems in various synchronization regimes and analytical results for detecting m
      : n phase synchrony are presented. Experimental applicability is demonstrated by
      detecting nonlinear interactions between neuronal local field potentials recorded
      in different parts of macaque visual cortex.

PMID- 23004852
TI  - Anticipated synchronization and the predict-prevent control method in the
      FitzHugh-Nagumo model system.
AB  - We study the synchronization region of two unidirectionally coupled FitzHugh
      Nagumo systems, in a master-slave configuration, under the influence of external
      forcing terms. In the particular region where the slave anticipates the dynamics
      of the master system, we observe that the synchronization is robust to the
      different types of forcings. We then use the predict-prevent control method to
      suppress unwanted pulses in the master system by using the information of the
      slave output. We find that this method is more efficient than the direct control
      method based on the master dynamics. Finally, we observe that a perfect matching
      between the parameters of the master and the slave is not necessary for the
      control to be efficient. Moreover, this parameter mismatch can, in some cases,
      improve the control.

PMID- 23004853
TI  - Extreme events in multivariate deterministic systems.
AB  - The probabilistic properties of extreme values in multivariate deterministic
      dynamical systems are analyzed. It is shown that owing to the intertwining of
      unstable and stable modes the effect of dynamical complexity on the extremes
      tends to be masked, in the sense that the cumulative probability distribution of
      typical variables is differentiable and its associated probability density is
      continuous. Still, there exist combinations of variables probing the dominant
      unstable modes displaying singular behavior in the form of nondifferentiability
      of the cumulative distributions of extremes on certain sets of phase space
      points. Analytic evaluations and extensive numerical simulations are carried out
      for characteristic examples of Kolmogorov-type systems, for low-dimensional
      chaotic flows, and for spatially extended systems.

PMID- 23004854
TI  - Pattern formation via intermittence from microscopic deterministic dynamics.
AB  - We propose a one-dimensional lattice model, inspired by population dynamics
      interaction. The model combines a variable coupling range with the Allee effect.
      The system is capable of exhibiting pattern formation that is similar to what
      occurs in similar continuous models for population dynamics. However, the
      formation features are quite different; in this case the pattern emerges from a
      disorder state via intermittence. We analytically estimated the selected
      wavelength of the formed pattern and numerically studied fluctuations around the
      mean wavelength. We also comment on the relationship between intermittence and
      the edge of chaos as well as sensitivity to initial conditions. Next, we present
      an analytical prediction of the influence of the world size on the intermittent
      regime which is in good agreement with the numerical observations. Moreover, the
      last calculation provided us an alternative way to compute the pattern
      wavelength. Finally, we discuss the continuous limit of our lattice model.

PMID- 23004855
TI  - Localization properties of covariant Lyapunov vectors for quasi-one-dimensional
      hard disks.
AB  - The Lyapunov exponent spectrum and covariant Lyapunov vectors are studied for a
      quasi-one-dimensional system of hard disks as a function of density and system
      size. We characterize the system using the angle distributions between covariant
      vectors and the localization properties of both Gram-Schmidt and covariant
      vectors. At low density there is a kinetic regime that has simple scaling
      properties for the Lyapunov exponents and the average localization for part of
      the spectrum. This regime shows strong localization in a proportion of the first
      Gram-Schmidt and covariant vectors and this can be understood as highly localized
      configurations dominating the vector. The distribution of angles between
      neighboring covariant vectors has characteristic shapes depending upon the
      difference in vector number, which vary over the continuous region of the
      spectrum. At dense gas- or liquid-like densities the behavior of the covariant
      vectors are quite different. The possibility of tangencies between different
      components of the unstable manifold and between the stable and unstable manifolds
      is explored but it appears that exact tangencies do not occur for a generic
      chaotic trajectory.

PMID- 23004856
TI  - Forecasting synchronizability of complex networks from data.
AB  - Given a complex networked system whose topology and dynamical equations are
      unknown, is it possible to foresee that a certain type of collective dynamics can
      potentially emerge in the system, provided that only time-series measurements are
      available? We address this question by focusing on a commonly studied type of
      collective dynamics, namely, synchronization in coupled dynamical networks. We
      demonstrate that, using the compressive-sensing paradigm, even when the coupling
      strength is not uniform so that the network is effectively weighted, the full
      topology, the coupling weights, and the nodal dynamical equations can all be
      uncovered accurately. The reconstruction accuracy and data requirement are
      systematically analyzed, in a process that includes a validation of the
      reconstructed eigenvalue spectrum of the underlying coupling matrix. A master
      stability function (MSF), the fundamental quantity determining the network
      synchronizability, can then be calculated based on the reconstructed dynamical
      system, the accuracy of which can be assessed as well. With the coupling matrix
      and MSF fully uncovered, the emergence of synchronous dynamics in the network can
      be anticipated and controlled. To forecast the collective dynamics on complex
      networks is an extremely challenging problem with significant applications in
      many disciplines, and our work represents an initial step in this important area.

PMID- 23004857
TI  - Unidirectional motion of a water nanodroplet subjected to a surface energy
      gradient.
AB  - We perform molecular dynamics simulations to demonstrate that when a nanodroplet
      is confined inside a carbon nanotube (CNT), unidirectional motion can be created
      by a nonzero surface energy gradient. It is found that the water nanodroplet
      moves along the direction of increasing surface energy. The transportation
      efficiency of the water nanodroplet is found to be dependent on the surface
      energy gradient; environmental temperature; and the flexibility, diameter, and
      defectiveness of the CNT. It is shown that higher surface energy gradient, the
      smaller diameter of the CNT, and fewer defects promote higher transportation
      efficiency. However, when the temperature is too high or too low, the water
      transport across the CNT is impeded. Except for the initial stage at the
      relatively low environmental temperature, higher flexibility of the CNT wall
      reduces the transportation efficiency. It is also found that the hydrogen bonds
      of water molecules play a role in the dynamic acceleration process with a
      wavelike feature. The present work provides insight for the development of CNT
      devices for applications such as drug delivery, nanopumps, chemical process
      control, and molecular medicine.

PMID- 23004858
TI  - Electrokinetically induced alterations in dynamic response of viscoelastic fluids
      in narrow confinements.
AB  - We investigate a dynamical interplay between interfacial electrokinetics and a
      combined dissipative and elastic behavior of flow through narrow confinements, in
      analogy with spatiotemporal hydrodynamics of porous media. In particular, we
      investigate the effects of streaming potential on the pertinent dynamic
      responses, by choosing a Maxwell fluid model for representing the consequent
      electro-hydrodynamic characteristics. We transform the pertinent governing
      equation to the frequency domain, so that a dynamic generalization of Darcy's law
      in the presence of streaming potential effects can be effectively realized. We
      show that the frequencies corresponding to local maxima in the dynamic
      permeability also correspond to local maxima in the induced streaming potential.
      We also bring out the effects of Stern layer conductivity on the dynamic
      permeability. Our analytical estimates do reveal that serious overestimations in
      the commonly portrayed notion of massive amplifications of dynamic permeability
      at resonating frequencies may be possible, if interactions between spontaneous
      electrochemical interfacial phenomena and pulsating pressure-gradient-driven
      viscoelastic transport are trivially ignored.

PMID- 23004859
TI  - Collapse of a nanoscopic void triggered by a spherically symmetric traveling
      sound wave.
AB  - Molecular-dynamics simulations of the Lennard-Jones fluid (up to 10(7) atoms) are
      used to analyze the collapse of a nanoscopic bubble. The collapse is triggered by
      a traveling sound wave that forms a shock wave at the interface. The peak
      temperature T(max) in the focal point of the collapse is approximately
      SigmaR(0)(a), where Sigma is the surface density of energy injected at the
      boundary of the container of radius R(0) and alpha ~ 0.4-0.45. For Sigma = 1.6
      J/m(2) and R(0) = 51 nm, the shock wave velocity, which is proportional to
      ?Sigma, reaches 3400 m/s (4 times the speed of sound in the liquid); the pressure
      at the interface, which is proportional to Sigma, reaches 10 GPa; and T(max)
      reaches 40,000 K. The Rayleigh-Plesset equation together with the time of the
      collapse can be used to estimate the pressure at the front of the shock wave.

PMID- 23004860
TI  - Phase transitions and marginal ensemble equivalence for freely evolving flows on
      a rotating sphere.
AB  - The large-scale circulation of planetary atmospheres such as that of the Earth is
      traditionally thought of in a dynamical framework. Here we apply the statistical
      mechanics theory of turbulent flows to a simplified model of the global
      atmosphere, the quasigeostrophic model, leading to nontrivial equilibria.
      Depending on a few global parameters, the structure of the flow may be either a
      solid-body rotation (zonal flow) or a dipole. A second-order phase transition
      occurs between these two phases, with associated spontaneous symmetry breaking in
      the dipole phase. This model allows us to go beyond the general theory of
      marginal ensemble equivalence through the notion of Goldstone modes.

PMID- 23004861
TI  - Characteristic spatial scale of vesicle pair interactions in a plane linear flow.
AB  - We report the experimental studies on interaction of two vesicles trapped in a
      microfluidic four-roll mill, where a plane linear flow is realized. We found that
      the dynamics of a vesicle in tank-treading motion is significantly altered by the
      presence of another vesicle at separation distances up to 3.2-3.7 times of the
      vesicle effective radius. This result is supported by measurement of a single
      vesicle back-reaction on the velocity field. Thus the experiment provides the
      upper bound for the volume fraction phi = 0.08-0.13 of noninteracting vesicle
      suspensions.

PMID- 23004862
TI  - Localized modulation of rotating waves in Taylor-Couette flow.
AB  - We report the results of an experimental study on the multiplicity of states in
      Taylor-Couette flow as a result of axial localization of azimuthally rotating
      waves. Localized states have been found to appear hysteretically from time
      dependent Taylor-Couette flow at Reynolds numbers significantly above the onset
      of wavy Taylor vortices. These localized states have the shape of a modulated
      rotating wave and differ significantly from global modulated wavy Taylor vortex
      states in their spatial characteristics. Axial localization of rotating waves is
      accompanied with a significant increase in size of the underlying pair of Taylor
      vortices. Our work reveals that localization provides a mechanism for the
      appearance of multiple time-dependent states in Taylor-Couette flow.

PMID- 23004863
TI  - Three-dimensional numerical simulation of vesicle dynamics using a front-tracking
      method.
AB  - Three-dimensional numerical simulation using the front-tracking method is
      presented on the dynamics of a vesicle in a linear shear flow. The focus here is
      to elucidate the parametric dependence and the self-similarity of the vesicle
      dynamics, quantification of vesicle deformation, and the analysis of shape
      dynamics. A detailed comparison of the numerical results is made with various
      theoretical models and experiments. It is found that the applicability of the
      theoretical models is limited despite some general agreement with the simulations
      and experiments. The deviations between the perturbative results and the
      simulation results occur even in the absence of thermal noise. Specifically, we
      find that the vesicle dynamics does not follow a self-similar behavior in a two
      parameter phase space, as proposed in a theoretical model. Rather, the dynamics
      is governed by three controlling parameters, namely, the excess area, viscosity
      ratio, and dimensionless shear rate. Additionally, we find that a linear scaling
      of the tank-treading angle, as proposed in the theoretical model, is possible
      only for nearly spherical vesicles. The breakdown of the scaling occurs at higher
      values of the excess area even in the absence of thermal noise. We find that the
      vesicle deformation saturates at large shear rates, and the asymptotic
      deformation matches well with a theoretical prediction for nearly spherical
      vesicles. The dependence of the critical viscosity ratio associated with the
      onset of unsteady dynamics on the vesicle excess area is in excellent agreement
      with the experimental observation. We show that near the transition between the
      tank-treading and tumbling dynamics, both the vacillating-breathing-like motion
      characterized by a smooth ellipsoidal shape and the trembling-like motion
      characterized by a highly deformed shape are possible. For the trembling-like
      motion, the shape is highly three-dimensional with concavities and lobes, and the
      vesicle deforms more in the vorticity direction than in the shear plane. A
      Fourier spectral analysis of the vesicle shape shows the presence of the odd
      harmonics and higher order modes beyond fourth order.

PMID- 23004864
TI  - Emergence of a limit cycle for swimming microorganisms in a vortical flow of a
      viscoelastic fluid.
AB  - We propose that the rheological properties of background fluid play an important
      role in the interaction of microorganisms with the flow field. The viscoelastic
      induced migration of microorganisms in a vortical flow leads to the emergence of
      a limit cycle. The shape and formation rate of patterns depend on motility,
      vorticity strength, and rheological properties of the background fluid. Given the
      inherent viscoelasticity of exopolysaccharides secreted by microorganisms, our
      results can suggest new mechanisms leading to the vital behavior of
      microorganisms such as bacterial aggregation and biofilm formation.

PMID- 23004865
TI  - Thermal and second-law analysis of a micro- or nanocavity using direct-simulation
      Monte Carlo.
AB  - In this study the direct-simulation Monte Carlo (DSMC) method is utilized to
      investigate thermal characteristics of micro- or nanocavity flow. The rarefied
      cavity flow shows unconventional behaviors which cannot be predicted by the
      Fourier law, the constitutive relation for the continuum heat transfer. Our
      analysis in this study confirms some recent observations and shows that the
      gaseous flow near the top-left corner of the cavity is in a strong nonequilibrium
      state even within the early slip regime, Kn=0.005. As we obtained slip velocity
      and temperature jump on the driven lid of the cavity, we reported meaningful
      discrepancies between the direct and macroscopic sampling of rarefied flow
      properties in the DSMC method due to existence of nonequilibrium effects in the
      corners of cavity. The existence of unconventional nonequilibrium heat transfer
      mechanisms in the middle of slip regime, Kn=0.05, results in the appearance of
      cold-to-hot heat transfer in the microcavity. In the current study we demonstrate
      that existence of such unconventional heat transfer is strongly dependent on the
      Reynolds number and it vanishes in the large values of the lid velocity. As we
      compared DSMC solution with the results of regularized 13 moments (R13)
      equations, we showed that the thermal characteristic of the microcavity obtained
      by the R13 method coincides with the DSMC prediction. Our investigation also
      includes the analysis of molecular entropy in the microcavity to explain the heat
      transfer mechanism with the aid of the second law of thermodynamics. To this aim,
      we obtained the two-dimensional velocity distribution functions to report the
      molecular-based entropy distribution, and show that the cold-to-hot heat transfer
      in the cavity is well in accordance with the second law of thermodynamics and
      takes place in the direction of increasing entropy. At the end we introduce the
      entropy density for the rarefied flow and show that it can accurately illustrate
      departure from the equilibrium state.

PMID- 23004866
TI  - Magnetic control of Leidenfrost drops.
AB  - We show how a magnetic field can influence the motion of a paramagnetic drop made
      of liquid oxygen in a Leidenfrost state on solids at room temperature. It is
      demonstrated that the trajectory can be modified in both direction and velocity
      and that the results can be interpreted in terms of classical mechanics as long
      as the drop does not get too close to the magnet. We study the deviation and
      report that it can easily overcome 180? and even diverge under certain
      conditions, leading to situations where a drop gets captured. In the vicinity of
      the magnet, another type of trapping is observed, due to the deformation of the
      drop in this region, which leads to a strong energy dissipation. Conversely,
      drops can be accelerated by moving magnets (slingshot effect).

PMID- 23004867
TI  - Regimes of chemical reaction waves initiated by nonuniform initial conditions for
      detailed chemical reaction models.
AB  - Regimes of chemical reaction wave propagation initiated by initial temperature
      nonuniformity in gaseous mixtures, whose chemistry is governed by chain-branching
      kinetics, are studied using a multispecies transport model and a detailed
      chemical model. Possible regimes of reaction wave propagation are identified for
      stoichiometric hydrogen-oxygen and hydrogen-air mixtures in a wide range of
      initial pressures and temperature levels, depending on the initial non-uniformity
      steepness. The limits of the regimes of reaction wave propagation depend upon the
      values of the spontaneous wave speed and the characteristic velocities of the
      problem. It is shown that one-step kinetics cannot reproduce either quantitative
      neither qualitative features of the ignition process in real gaseous mixtures
      because the difference between the induction time and the time when the
      exothermic reaction begins significantly affects the ignition, evolution, and
      coupling of the spontaneous reaction wave and the pressure wave, especially at
      lower temperatures. We show that all the regimes initiated by the temperature
      gradient occur for much shallower temperature gradients than predicted by a one
      step model. The difference is very large for lower initial pressures and for
      slowly reacting mixtures. In this way the paper provides an answer to questions,
      important in practice, about the ignition energy, its distribution, and the scale
      of the initial nonuniformity required for ignition in one or another regime of
      combustion wave propagation.

PMID- 23004868
TI  - Nanoelectromechanical devices in a fluidic environment.
AB  - We present a comprehensive study of nanoelectromechanical systems in pressurized
      fluids. Resonant responses and quality factors are monitored in five different
      gases and one liquid, in pressures ranging from vacuum to 20 MPa, in order to
      evaluate theoretical models of device-fluid interactions at the nanoscale. The
      traditional Newell picture of microresonator damping in different pressure
      regimes is found to be inadequate in describing nanoresonators in general.
      Damping at intermediate pressure ranges is better physically characterized by a
      Weissenberg number (which compares oscillation frequencies with fluid relaxation
      rates) than a Knudsen number (which compares mean free paths with device widths)
      and most adequately described by the Yakhot and Colosqui model. At high-pressure
      ranges, two models are found to give good agreement with data: the
      phenomenological model of vibrating spheres and the Sader and Bhiladvala model
      for the viscous regime. The latter is also successful in explicitly predicting
      pressure-dependent behavior of the viscous mass load and damping. We observe
      significant increases in damping due to the squeezed film (SF) of gas between the
      device and substrate as well as due to undercut (an unavoidable artifact of the
      standard fabrication technique); correcting the shape of the devices with a
      focused ion beam allows us to differentiate these two factors. Application of the
      SF model accounts well for additional damping at high pressures while only
      qualitatively agreeing at lower pressures. The extensive data collected allow
      additional insight into fundamental processes underlying fluid damping at the
      nanoscale, particularly in the intermediate- and high-pressure regimes.

PMID- 23004869
TI  - Map of fluid flow in fractal porous medium into fractal continuum flow.
AB  - This paper is devoted to fractal continuum hydrodynamics and its application to
      model fluid flows in fractally permeable reservoirs. Hydrodynamics of fractal
      continuum flow is developed on the basis of a self-consistent model of fractal
      continuum employing vector local fractional differential operators allied with
      the Hausdorff derivative. The generalized forms of Green-Gauss and Kelvin-Stokes
      theorems for fractional calculus are proved. The Hausdorff material derivative is
      defined and the form of Reynolds transport theorem for fractal continuum flow is
      obtained. The fundamental conservation laws for a fractal continuum flow are
      established. The Stokes law and the analog of Darcy's law for fractal continuum
      flow are suggested. The pressure-transient equation accounting the fractal metric
      of fractal continuum flow is derived. The generalization of the pressure
      transient equation accounting the fractal topology of fractal continuum flow is
      proposed. The mapping of fluid flow in a fractally permeable medium into a
      fractal continuum flow is discussed. It is stated that the spectral dimension of
      the fractal continuum flow d(s) is equal to its mass fractal dimension D, even
      when the spectral dimension of the fractally porous or fissured medium is less
      than D. A comparison of the fractal continuum flow approach with other models of
      fluid flow in fractally permeable media and the experimental field data for
      reservoir tests are provided.

PMID- 23004870
TI  - Inverse energy cascade and turbulent transport in a quasi-two-dimensional
      magnetized electrolyte system: an experimental study.
AB  - We present an experimental study of the inverse energy cascade, spectral
      condensation, and turbulent particle transport in an electromagnetically driven
      thin layer of NaCl electrolyte. The presence of the bottom friction provides an
      energy sink at large scales for the turbulent flow. This energy sink crucially
      contributes to the balance of the forcing and dissipation which makes the inverse
      cascade steady. The present work provides an estimation of the linear dissipation
      rate on an experimental basis. We also show how the dissipation rate affects the
      characteristic features of the velocity spectrum and the dynamics of the spectral
      condensation. A quantitative study of the turbulent diffusion shows a significant
      decrease of the radial transport during the spectral condensation process.

PMID- 23004871
TI  - Flow over a traveling wavy foil with a passively flapping flat plate.
AB  - Flow over a traveling wavy foil with a passively flapping flat plate has been
      investigated using a multiblock lattice Boltzmann equation and the immersed
      boundary method. The foil undergoes prescribed undulations in the lateral
      direction and the rigid flat plate has passive motion determined by the fluid
      structure interaction. This simplified model is used to study the effect of the
      fish caudal fin and its flexibility on the locomotion of swimming animals. The
      flexibility of the caudal fin is modeled by a torsion spring acting about the
      pivot at the conjuncture of the wavy foil and the flat plate. The study reveals
      that the passively oscillating flat plate contributes half of the propulsive
      force. The flexibility, represented by the nondimensional natural frequency F,
      plays a very important role in the movement and propulsive force generation of
      the whole body. When the plate is too flexible, the drag force is observed. As
      the flat plate becomes more rigid, the propulsive force that is generated when
      the undulation is confined to last part of the wavy foil becomes larger. The
      steady movement occurs at F=5. These results are consistent with the observations
      of some swimming animals in nature.

PMID- 23004872
TI  - Vortex filament model and multifractal conjecture.
AB  - We develop a theory of turbulence based on the inviscid Navier-Stokes equation.
      We get a simple but exact stochastic solution (vortex filament model) which
      allows us to obtain a power law for velocity structure functions in the inertial
      range. Combining the model with the multifractal conjecture, we calculate the
      scaling exponents without using the extended self-similarity approach. The
      results obtained are shown to be in very good agreement with numerical
      simulations and experimental data. The role of more general stochastic solutions
      of the Navier-Stokes equation is discussed.

PMID- 23004873
TI  - Recombination and enhanced metastable repopulation in the argon afterglow.
AB  - The power-off phase of pulsed low-pressure plasmas (the so-called afterglow) in
      noble gases is a rich field for both fundamental and application oriented
      research. The physics of these plasmas is complex and involves various processes:
      Initially, electrons cool rapidly to temperatures close to the gas temperature by
      evaporative cooling. At sufficiently high plasma densities the low kinetic
      electron energy strongly enhances three-body recombination into Rydberg states.
      Finally, subsequent collisional-radiative decay leads to emission of radiation
      and populates the metastable states of the atoms. The various steps are
      investigated experimentally and are compared to analytical models. This allows us
      to follow all steps throughout in a single experiment involving diagnostics of
      electron density, metastable density, and emission. Excellent agreement with the
      models is achieved. The mechanisms included are: (i) for electrons, balance
      between evaporative cooling and Coulomb collisions with ions leading to
      thermalization; (ii) consistent combination of re-ionization and microfield
      reduction of the ionization energy in the recombination rate; (iii) adiabatic
      balance of recombination and collisional and radiative de-excitation; and (iv)
      radiative population and diffusional and pooling collisional loss of metastable
      levels. Although the experiment is carried out in argon, the underlying physics
      is generally applicable for the afterglow of high-density low-pressure discharges
      in atomic gases.

PMID- 23004874
TI  - Density functional theory for the ground state of spherically confined dusty
      plasma.
AB  - The spatial structure of dusty plasma confined in a spherical microcavity has
      been investigated by use of the density functional theory for classical fluids,
      in which all particles undergo an isotropic harmonic potential and the
      interparticle interaction is described by the hard-core Yukawa potential. The
      fundamental measure theory of Rosenfeld and its modified versions have been used
      in the energy functional to incorporate hard-core interactions between particles.
      Based on the variational principle, the equilibrium density profile can be
      obtained by use of an iteration calculation with the average density of particles
      as an input. In terms of density profiles presented under various conditions, the
      roles of the trapped parameter, coupling parameter, screening parameter, and the
      average number density of particles are discussed, and significant influences of
      these factors on the structure of confined dusty plasma are found.

PMID- 23004875
TI  - Time-dependent ionization models designed for intense and short laser pulse
      propagation in dielectric materials.
AB  - When an intense and short laser pulse propagates in a dielectric material,
      significant production of conduction electrons through multiphoton absorption
      (MPA) may occur. In addition to the laser intensity, the MPA process depends
      mainly on the laser frequency spectrum which may evolve significantly during the
      course of laser propagation in the material. Simple models for MPA accounting for
      possible time-dependent evolution of the laser frequency spectrum (as harmonic
      generation, chirping or broadening) are addressed. The first model is based on
      Bloch-Volkov states whereas the second approach relies on the density matrix
      formalism which has been adapted for the present study. Both models are well
      adapted for their introduction in a propagation code and are shown to correctly
      account for the MPA process whatever the characteristics of the laser frequency
      spectrum. The reliability of these approaches has been studied in two cases of
      practical interest. First, in the case where a second harmonic is present within
      the fundamental pulse, calculations show that the ionization rate may be
      significantly enhanced. Second, in the case of a chirped pulse, models are shown
      to correctly account for possible change in the multiphoton order during the
      course of interaction.

PMID- 23004876
TI  - Modeling of microwave-induced plasma in argon at atmospheric pressure.
AB  - A two-dimensional model of microwave-induced plasma (field frequency 2.45 GHz) in
      argon at atmospheric pressure is presented. The model describes in a self
      consistent manner the gas flow and heat transfer, the in-coupling of the
      microwave energy into the plasma, and the reaction kinetics relevant to high
      pressure argon plasma including the contribution of molecular ion species. The
      model provides the gas and electron temperature distributions, the electron, ion,
      and excited state number densities, and the power deposited into the plasma for
      given gas flow rate and temperature at the inlet, and input power of the incoming
      TEM microwave. For flow rate and absorbed microwave power typical for analytical
      applications (200-400 ml/min and 20 W), the plasma is far from thermodynamic
      equilibrium. The gas temperature reaches values above 2000 K in the plasma
      region, while the electron temperature is about 1 eV. The electron density
      reaches a maximum value of about 4 * 10(21) m(-3). The balance of the charged
      particles is essentially controlled by the kinetics of the molecular ions. For
      temperatures above 1200 K, quasineutrality of the plasma is provided by the
      atomic ions, and below 1200 K the molecular ion density exceeds the atomic ion
      density and a contraction of the discharge is observed. Comparison with
      experimental data is presented which demonstrates good quantitative and
      qualitative agreement.

PMID- 23004877
TI  - Self-confinement of finite dust clusters in isotropic plasmas.
AB  - Finite two-dimensional dust clusters are systems of a small number of charged
      grains. The self-confinement of dust clusters in isotropic plasmas is studied
      using the particle-in-cell method. The energetically favorable configurations of
      grains in plasma are found that are due to the kinetic effects of plasma ions and
      electrons. The self-confinement phenomenon is attributed to the change in the
      plasma composition within a dust cluster resulting in grain attraction mediated
      by plasma ions. This is a self-consistent state of a dust cluster in which
      grain's repulsion is compensated by the reduced charge and floating potential on
      grains, overlapped ion clouds, and depleted electrons within a cluster. The
      common potential well is formed trapping dust clusters in the confined state.
      These results provide both valuable insights and a different perspective to the
      classical view on the formation of boundary-free dust clusters in isotropic
      plasmas.

PMID- 23004878
TI  - Binding energy levels of a slowly moving ion in quantum plasmas.
AB  - Electrostatic potential of a slowly moving ion in quantum plasmas is studied.
      This potential is composed of the Debye-Huckel potential and the wake potential.
      The near-field-wake potential is found. The binding energy levels of one-electron
      bound states of the ion are calculated by use of the Ritz variation method. The
      trial wave function contains three variational parameters. The presence of the
      wake field splits the binding energy levels. This effect is analogous to the
      Zeeman effect. The removal of the degeneracy of binding energy levels is
      influenced by the speed of ion and the number density of electrons. Compared with
      binding energy levels of a free ion, some binding energy levels of a moving ion
      in quantum plasmas are "pushed up."

PMID- 23004879
TI  - Comparative merits of the memory function and dynamic local-field correction of
      the classical one-component plasma.
AB  - The complementarity of the liquid and plasma descriptions of the classical one
      component plasma is explored by studying wave number and frequency dependent
      dynamical quantities: the dynamical structure factor (DSF) and the dynamic local
      field correction (LFC). Accurate molecular dynamics (MD) simulations are used to
      validate and test models of the DSF and LFC. Our simulations, which span the
      entire fluid regime (Gamma=0.1-175), show that the DSF is very well represented
      by a simple and well known memory function model of generalized hydrodynamics. On
      the other hand, the LFC, which we have computed using MD for the first time, is
      not well described by existing models.

PMID- 23004880
TI  - Beyond the Child-Langmuir limit.
AB  - This article presents a new formulation of the solution for fully nonlinear and
      unsteady planar flow of an electron beam in a diode. Using characteristic
      variables (i.e., variables that follow particle paths) the solution is expressed
      through an exact analytic, but implicit, formula for any choice of incoming
      velocity v(0), electric field E(0), and current J(0). For steady solutions, this
      approach clarifies the origin of the maximal current J(max), derived by Child and
      Langmuir for v(0) = 0 and by Jaffe for v(0) > 0. The implicit formulation is used
      to find (1) unsteady solutions having constant incoming flux J(0) > J(max), which
      leads to formation of a virtual cathode, and (2) time-periodic solutions whose
      average flux exceeds the adiabatic average of J(max).

PMID- 23004881
TI  - Photoelectric Franck-Hertz experiment and its kinetic analysis by Monte Carlo
      simulation.
AB  - The electrical characteristics of a photoelectric Franck-Hertz cell are measured
      in argon gas over a wide range of pressure, covering conditions where elastic
      collisions play an important role, as well as conditions where ionization becomes
      significant. Photoelectron pulses are induced by the fourth harmonic UV light of
      a diode-pumped Nd:YAG laser. The electron kinetics, which is far more complex
      compared to the naive picture of the Franck-Hertz experiment, is analyzed via
      Monte Carlo simulation. The computations provide the electrical characteristics
      of the cell, the energy and velocity distribution functions, and the transport
      parameters of the electrons, as well as the rate coefficients of different
      elementary processes. A good agreement is obtained between the cell's measured
      and calculated electrical characteristics, the peculiarities of which are
      understood by the simulation studies.

PMID- 23004882
TI  - Dynamical-systems approach to relativistic nonlinear wave-particle interaction in
      collisionless plasmas.
AB  - In this report, we present a dynamical systems approach to study the exact
      nonlinear wave-particle interaction in relativistic regime. We give particular
      attention to the effect of wave obliquity on the dynamics of the orbits by
      studying the specific cases of parallel (theta = 0) and perpendicular (theta = 
      pi/2) propagations in comparison to the general case of oblique propagation theta
      =]-pi/2,0[. We found that the fixed points of the system correspond to Landau
      resonance and that the dynamics can evolve from trapping to surfatron
      acceleration for propagation angles obeying a Hopf bifurcations condition.
      Cyclotron-resonant particles are also studied by the construction of a pseudo
      potential structure in the Lorentz factor gamma. We derived a condition for which
      Arnold diffusion results in relativistic stochastic acceleration. Hence, two
      general conclusions are drawn: (1) The propagation angle theta can significantly
      alter the dynamics of the orbits at both Landau and cyclotron-resonances. (2)
      Considering the short-time scales upon which the particles are accelerated, these
      two mechanisms for Landau and cyclotron resonant orbits could become potential
      candidates for problems of particle energization in collisionless space and
      cosmic plasmas.

PMID- 23004883
TI  - Relativistic Klein-Gordon-Maxwell multistream model for quantum plasmas.
AB  - A multistream model for spinless electrons in a relativistic quantum plasma is
      introduced by means of a suitable fluidlike version of the Klein-Gordon-Maxwell
      system. The one- and two-stream cases are treated in detail. A new linear
      instability condition for two-stream quantum plasmas is obtained, generalizing
      the previously known nonrelativistic results. In both the one- and two-stream
      cases, steady-state solutions reduce the model to a set of coupled nonlinear
      ordinary differential equations, which can be numerically solved, yielding a
      manifold of nonlinear periodic and soliton structures. The validity conditions
      for the applicability of the model are addressed.

PMID- 23004884
TI  - Phase-space contraction and attractors for ultrarelativistic electrons.
AB  - Ultrashort-pulse laser intensities can reach 10(22) W/cm(2). In this case the
      electron motion becomes ultrarelativistic and significant bremsstrahlung occurs.
      The radiation causes a dissipative effect, which is called a radiation reaction.
      It has been shown in the literature that the radiation reaction force causes
      phase-space contraction when the motion of electrons in a laser field is
      considered. The effect of the radiation reaction force is smaller for electron
      propagation in the direction of a propagating plane wave compared to
      counterpropagation. In the case of two colliding laser beams with sufficiently
      large amplitudes, stochastic heating is an important process that will be
      influenced by the radiation reaction. It is shown here that the radiation
      reaction causes attractors and in certain parameter regimes electron motion
      converges to regular attractors. This causes a significant reduction of
      stochastic heating. The forms of the attractors are presented. The results
      confirm the general prediction of phase-space contraction and provide
      quantitative results for the speed of contraction as well as the type of
      attracted motion.

PMID- 23004885
TI  - Dust ion-acoustic solitary waves in a dusty plasma with nonextensive electrons.
AB  - The dust-modified ion-acoustic waves of Shukla and Silin are revisited within the
      theoretical framework of the Tsallis statistical mechanics. Nonextensivity may
      originate from correlation or long-range plasma interactions. Interestingly, we
      find that owing to electron nonextensivity, dust ion-acoustic (DIA) solitary
      waves may exhibit either compression or rarefaction. Our analysis is then
      extended to include self-consistent dust charge fluctuation. In this connection,
      the correct nonextensive electron charging current is rederived. The Korteweg-de
      Vries equation, as well as the Korteweg-de Vries-Burgers equation, is obtained,
      making use of the reductive perturbation method. The DIA waves are then analyzed
      for parameters corresponding to space dusty plasma situations.

PMID- 23004886
TI  - Instabilities for a relativistic electron beam interacting with a laser
      irradiated plasma.
AB  - The effects of a radiation field (RF) on the unstable modes developed in a
      relativistic electron beam-plasma interaction are investigated assuming that
      omega(0) > omega(p), where omega(0) is the frequency of the RF and omega(p) is
      the plasma frequency. These unstable modes are parametrically coupled to each
      other due to the RF and are a mix between two-stream and parametric
      instabilities. The dispersion equations are derived by the linearization of the
      kinetic equations for a beam-plasma system as well as the Maxwell equations. In
      order to highlight the effect of the radiation field we present a comparison of
      our analytical and numerical results obtained for nonzero RF with those for
      vanishing RF. Assuming that the drift velocity u(b) of the beam is parallel to
      the wave vector k of the excitations two particular transversal and parallel
      configurations of the polarization vector E(0) of the RF with respect to k are
      considered in detail. It is shown that in both geometries resonant and
      nonresonant couplings between different modes are possible. The largest growth
      rates are expected at the transversal configuration when E(0) is perpendicular to
      k. In this case it is demonstrated that, in general, the spectrum of the unstable
      modes in the omega-k plane is split into two distinct domains with long and short
      wavelengths, where the unstable modes are mainly sensitive to the beam or the RF
      parameters, respectively. In the parallel configuration, E(0)?k, and at short
      wavelengths the growth rates of the unstable modes are sensitive to both beam and
      RF parameters remaining insensitive to the RF at long wavelengths.

PMID- 23004887
TI  - Electron refluxing and K-shell line emission from Ti foils irradiated with
      subpicosecond laser pulses at 527 nm.
AB  - We present data on emission of K-shell radiation from Ti foils irradiated with
      subpicosecond pulses of second harmonic radiation (527 nm) from the TARANIS laser
      system at intensities of up to 10(18) W cm(-2). The data are used to demonstrate
      that a resonance absorption type mechanism is responsible for absorption of the
      laser light and to estimate fast electron temperatures of 30-60 keV that are in
      broad agreement with expectation from models of absorption for a steep density
      gradient. Data taken with resin-backed targets are used to demonstrate clear
      evidence of electron refluxing even at the modest fast electron temperatures
      inferred.

PMID- 23004888
TI  - Thermal effects on the propagation of large-amplitude electromagnetic waves in
      magnetized relativistic electron-positron plasma.
AB  - The propagation of circularly polarized electromagnetic waves along a constant
      background magnetic field in an electron-positron plasma is calculated by means
      of both a fluid and a kinetic theory treatment. In the fluid theory, relativistic
      effects are included in the particle motion, the wave field, and in the thermal
      motion by means of a function f, which depends only on the plasma temperature. In
      this work we analyze the consistency of the fluid results with those obtained
      from a kinetic treatment, based on the relativistic Vlasov equation. The
      corresponding kinetic dispersion relation is numerically studied for various
      temperatures, and results are compared with the fluid treatment. Analytic
      expressions for the Alfven velocity are obtained for the fluid and kinetic
      models, and it is shown that, in the kinetic treatment, the Alfven branch is
      suppressed for large temperatures.

PMID- 23004889
TI  - Stability of nonlinear normal modes in the Fermi-Pasta-Ulam beta chain in the
      thermodynamic limit.
AB  - All possible symmetry-determined nonlinear normal modes (also called simple
      periodic orbits, one-mode solutions, etc.) in both hard and soft Fermi-Pasta-Ulam
      beta chains are discussed. A general method for studying their stability in the
      thermodynamic limit as well as its application for each of the above nonlinear
      normal modes are presented.

PMID- 23004890
TI  - Electromagnetic forces on a discrete spherical invisibility cloak under time
      harmonic illumination.
AB  - We study electromagnetic forces and torques on a discrete spherical invisibility
      cloak under time-harmonic illumination. We consider the influence of material
      absorption and losses, and we show that while the impact of absorption on the
      optical force remains confined to frequencies near the absorption peak, its
      impact on the electromagnetic torque experienced by the cloak is spectrally
      broader and follows the spectrum of the absorption cross section of the cloak. We
      also investigate the mechanical shielding of a test particle within the cloak. We
      find that even an imperfect cloak can reduce the radiation pressure on the
      particle significantly; however, under certain conditions the force on the
      particle can be stronger than it would be in the absence of the cloak.

PMID- 23004891
TI  - Vortex solitons in defocusing media with spatially inhomogeneous nonlinearity.
AB  - The analytical two- and three-dimensional vortex solitons with arbitrary values
      of vorticity are constructed in the cubic defocusing media with spatially
      inhomogeneous nonlinearity. The values of the nonlinearity coefficients are zero
      near the center and increase rapidly toward the periphery. In addition to the
      analytical ones, a number of vortex solitons are found numerically. It is shown
      that analytical vortex solitons are stable. Also, the stability region of the
      numerically constructed vortex solitons are given.

PMID- 23004892
TI  - Interaction forces among two-dimensional bright solitons and many-soliton
      molecules.
AB  - We consider two-dimensional bright matter-wave solitons in two-dimensional Bose
      Einstein condensates. From the asymptotic form of their wave function, we derive
      an analytic expression for the force of interaction between solitons in the large
      separation limit, which turns out to decay with solitons separation Delta as
      F(Delta)?exp(-Delta)/?Delta. Simulating the dynamics of two solitons using the
      relevant Gross-Pitaevskii equation, we obtain the force of the interaction for
      the full range of Delta, which turns out to be of molecular type. We show that
      many-soliton molecules can exist as a result of such a molecular-type of
      interaction. These include string-shaped, ring-shaped, or regular-lattice-shaped
      soliton molecules. By calculating their binding energy, we investigate the
      stability of these structures. Contrary to one-dimensional soliton molecules,
      which have no binding energy, two-dimensional molecules of a lattice of solitons
      with alternating phases are robust and have a negative binding energy. Lattices
      of size larger than 2 * 2 solitons have many discrete equilibrium values of the
      separation between two neighboring solitons.

PMID- 23004893
TI  - Temporally and spatially resolved imaging of laser-nucleated bubble cloud
      sonoluminescence.
AB  - Imaging techniques have been used to capture the temporal and spatial evolution
      of light emissions from collapsing bubble clouds at high static pressures.
      Emission events lasting up to 70 ns with peak diameters nearing 1 mm have been
      observed. Observations of the cloud evolution before and after emission events
      have been made. Photomultiplier tube monitoring has been employed in conjunction
      with imaging to study the temporal characteristics of light emission.

PMID- 23004894
TI  - Electrical dark compacton generator: theory and simulations.
AB  - A modified Colpitts oscillator (MCO) associated with a nonlinear transmission
      line (NLTL) with intersite nonlinearity is introduced as a self-sustained
      generator of a train of modulated dark signals with compact shape. Equations of
      state describing the dynamics of the MCO part are derived and the stationary
      state is obtained. Using the Routh-Hurwitz criterion, the result of a stability
      analysis indicates the existence of a limit cycle in certain parameter regimes
      and there the oscillation of the circuit delivers pulselike electrical signals.
      The train of generated signals is then transformed into a train of compact
      modulated dark voltage solitons by the NLTL. The exactness of this analytical
      analysis is confirmed by numerical simulations performed on the circuit
      equations. Finally, simulations show the capacity of this circuit to work as a
      generator of compactlike dark voltage solitons. The performance of the generator,
      namely, the pulse width and the repetition rate, is controlled by the magnitude
      of the characteristic parameters of the electronic components of the device.

PMID- 23004895
TI  - Explicit solutions from eigenfunction symmetry of the Korteweg-de Vries equation.
AB  - In nonlinear science, it is very difficult to find exact interaction solutions
      among solitons and other kinds of complicated waves such as cnoidal waves and
      Painleve waves. Actually, even if for the most well-known prototypical models
      such as the Kortewet-de Vries (KdV) equation and the Kadomtsev-Petviashvili (KP)
      equation, this kind of problem has not yet been solved. In this paper, the
      explicit analytic interaction solutions between solitary waves and cnoidal waves
      are obtained through the localization procedure of nonlocal symmetries which are
      related to Darboux transformation for the well-known KdV equation. The same
      approach also yields some other types of interaction solutions among different
      types of solutions such as solitary waves, rational solutions, Bessel function
      solutions, and/or general Painleve II solutions.

PMID- 23004896
TI  - Matter-wave solutions in Bose-Einstein condensates with harmonic and Gaussian
      potentials.
AB  - We study exact matter-wave solutions of the quasi-one-dimensional Gross
      Pitaevskii (GP) equation with the space- and/or time-modulated potential and
      nonlinearity and the time-dependent gain or loss term in Bose-Einstein
      condensates. In particular, based on the similarity transformation and symbolic
      analysis, we report several families of exact solutions of the quasi-one
      dimensional GP equation in the combination of the harmonic and Gaussian
      potentials, in which some physically relevant solutions are described. The
      stability of the obtained matter-wave solutions is addressed numerically such
      that some stable solutions are found. Moreover, we also analyze the parameter
      regimes for the stable solutions. These results may raise the possibility of
      relative experiments and potential applications.

PMID- 23004897
TI  - Thin-film flows with moving contact lines: An approach to reducing computing
      time.
AB  - A numerical method to reduce the computing times of thin-film flows with moving
      contact lines is presented. The flows of a film and a droplet are calculated in a
      frame that moves with a nonconstant velocity U(t). The criterion employed to
      define this velocity is to reduce the maximum height change in the flow's most
      critical zone. The efficiency of the algorithm in reducing the CPU time is tested
      in gravity-driven flows, where the computing time is reduced by up to a factor of
      13 depending on the parameters of the problem.

PMID- 23004898
TI  - Modularity optimization by conformational space annealing.
AB  - We propose a modularity optimization method, Mod-CSA, based on stochastic global
      optimization algorithm, conformational space annealing (CSA). Our method
      outperforms simulated annealing in terms of both efficiency and accuracy, finding
      higher modularity partitions with less computational resources required. The high
      modularity values found by our method are higher than, or equal to, the largest
      values previously reported. In addition, the method can be combined with other
      heuristic methods, and implemented in parallel fashion, allowing it to be
      applicable to large graphs with more than 10,000 nodes.

PMID- 23004899
TI  - Transitions between imperfectly ordered crystalline structures: a phase switch
      Monte Carlo study.
AB  - A model for two-dimensional colloids confined laterally by "structured
      boundaries" (i.e., ones that impose a periodicity along the slit) is studied by
      Monte Carlo simulations. When the distance D between the confining walls is
      reduced at constant particle number from an initial value D(0), for which a
      crystalline structure commensurate with the imposed periodicity fits, to smaller
      values, a succession of phase transitions to imperfectly ordered structures
      occur. These structures have a reduced number of rows parallel to the boundaries
      (from n to n-1 to n-2, etc.) and are accompanied by an almost periodic strain
      pattern, due to "soliton staircases" along the boundaries. Since standard
      simulation studies of such transitions are hampered by huge hysteresis effects,
      we apply the phase switch Monte Carlo method to estimate the free energy
      difference between the structures as a function of the misfit between D and D(0),
      thereby locating where the transitions occur in equilibrium. For comparison, we
      also obtain this free energy difference from a thermodynamic integration method:
      The results agree, but the effort required to obtain the same accuracy as
      provided by phase switch Monte Carlo would be at least three orders of magnitude
      larger. We also show for a situation where several "candidate structures" exist
      for a phase, that phase switch Monte Carlo can clearly distinguish the metastable
      structures from the stable one. Finally, applying the method in the conjugate
      statistical ensemble (where the normal pressure conjugate to D is taken as an
      independent control variable), we show that the standard equivalence between the
      conjugate ensembles of statistical mechanics is violated.

PMID- 23004900
TI  - Evaluation of the physical annealing strategy for simulated annealing: a function
      based analysis in the landscape paradigm.
AB  - The effectiveness of the actual annealing strategy in finite-time optimization by
      simulated annealing (SA) is analyzed by focusing on the search function of the
      relaxation dynamics observed in the multimodal landscape of the cost function.
      The rate-cycling experiment, which was introduced in the previous study [M.
      Hasegawa, Phys. Rev. E 83, 036708 (2011)] to examine the role of the relaxation
      dynamics in optimization, and the temperature-cycling experiment, which was
      developed for a laboratory experiment on relaxation-related phenomena, are
      conducted on two types of random traveling salesman problems (TSPs). In each
      experiment, the SA search starting from a quenched solution is performed
      systematically under a nonmonotonic temperature control used in the actual heat
      treatment of metals and glasses. The results show that, as in the previous
      monotonic cooling from a random solution, the optimizing ability is enhanced by
      allocating a lot of time to the search performed near an effective intermediate
      temperature irrespective of the annealing technique. In this productive phase,
      the relaxation dynamics successfully function as an optimizer and the relevant
      characteristics analogous to the stabilization phenomenon and the acceleration of
      relaxation, which are observed in glass-forming materials, play favorable roles
      in the present optimization. This nonmonotonic approach also has the advantage of
      a wider operation range of the effective relaxation dynamics, and in conclusion,
      the actual annealing strategy is useful and more workable than the conventional
      slow-cooling strategy, at least for the present TSPs. Further discussion is given
      of an illuminating aspect of computational physics analysis in the optimization
      algorithm research.

PMID- 23004901
TI  - Control-volume representation of molecular dynamics.
AB  - A molecular dynamics (MD) parallel to the control volume (CV) formulation of
      fluid mechanics is developed by integrating the formulas of Irving and Kirkwood
      [J. Chem. Phys. 18, 817 (1950)] over a finite cubic volume of molecular
      dimensions. The Lagrangian molecular system is expressed in terms of an Eulerian
      CV, which yields an equivalent to Reynolds' transport theorem for the discrete
      system. This approach casts the dynamics of the molecular system into a form that
      can be readily compared to the continuum equations. The MD equations of motion
      are reinterpreted in terms of a Lagrangian-to-control-volume (LCV) conversion
      function theta(i) for each molecule i. The LCV function and its spatial
      derivatives are used to express fluxes and relevant forces across the control
      surfaces. The relationship between the local pressures computed using the volume
      average [Lutsko, J. Appl. Phys. 64, 1152 (1988)] techniques and the method of
      planes [Todd et al., Phys. Rev. E 52, 1627 (1995)] emerges naturally from the
      treatment. Numerical experiments using the MD CV method are reported for
      equilibrium and nonequilibrium (start-up Couette flow) model liquids, which
      demonstrate the advantages of the formulation. The CV formulation of the MD is
      shown to be exactly conservative and is, therefore, ideally suited to obtain
      macroscopic properties from a discrete system.

PMID- 23004902
TI  - Compressed sensing for phase retrieval.
AB  - To date there are several iterative techniques that enjoy moderate success when
      reconstructing phase information, where only intensity measurements are made.
      There remains, however, a number of cases in which conventional approaches are
      unsuccessful. In the last decade, the theory of compressed sensing has emerged
      and provides a route to solving convex optimisation problems exactly via l(1)
      norm minimization. Here the application of compressed sensing to phase retrieval
      in a nonconvex setting is reported. An algorithm is presented that applies
      reweighted l(1)-norm minimization to yield accurate reconstruction where
      conventional methods fail.

PMID- 23004903
TI  - Simulation of static critical phenomena in nonideal fluids with the lattice
      Boltzmann method.
AB  - A fluctuating nonideal fluid at its critical point is simulated with the lattice
      Boltzmann method. It is demonstrated that the method, employing a Ginzburg-Landau
      free energy functional, correctly reproduces the static critical behavior
      associated with the Ising universality class. A finite-size scaling analysis is
      applied to determine the critical exponents related to the order parameter,
      compressibility and specific heat. A particular focus is put on finite-size
      effects and issues related to the global conservation of the order parameter.

PMID- 23004904
TI  - Improving the efficiency of extended ensemble simulations: the accelerated weight
      histogram method.
AB  - We propose a method for efficient simulations in extended ensembles, useful,
      e.g., for the study of problems with complex energy landscapes and for free
      energy calculations. The main difficulty in such simulations is the estimation of
      the a priori unknown weight parameters needed to produce flat histograms. The
      method combines several complementary techniques, namely, a Gibbs sampler for the
      parameter moves, a reweighting procedure to optimize data use, and a Bayesian
      update allowing for systematic refinement of the free energy estimate. In a
      certain limit the scheme reduces to the 1/t algorithm of B. E. Belardinelli and
      V. D. Pereyra [Phys. Rev. E 75, 046701 (2007)]. The performance of the method is
      studied on the two-dimensional Ising model, where comparison with the exact free
      energy is possible, and on an Ising spin glass.

PMID- 23004905
TI  - Finding stable minima using a nudged-elastic-band-based optimization scheme.
AB  - Optimization is essential in many scientific and economical areas, but it is
      often too complex to be tackled by simple straightforward calculations or by
      trial and error. Two well-known methods to find low-lying minima in such complex
      systems are simulated annealing and the genetic algorithm. In these methods
      artificial fluctuations control the probability of the system to overcome a local
      minimum having a certain depth. Here we present a complementary scheme that is
      based on the nudged-elastic-band method ordinarily used to find saddle points and
      we apply the scheme to find the most stable isomers of the phosphorus P(4), P(8)
      molecules and the corresponding molecules of As(n), Sb(n), and Bi(n) (n = 4,8) in
      the framework of the density functional theory. In the case of n = 8 we have
      found stable and metastable configurations, some of which are new and have
      similar energies. As a by-product we obtained an upper bound for the energy
      barriers between these configurations.

PMID- 23004906
TI  - Mie scattering by soft core-shell particles and its applications to ellipsometric
      light scattering.
AB  - Through the use of Mie theory generalized to multiple spheres, the derivatives of
      the scattering matrix elements and ellipsometric scattering variables are found
      as a function of shell thickness and nonconcentricity for core-shell particles.
      In particular, for the case of a core-shell sphere system where the centers are
      not concentric, the derivatives are taken with respect to the line segment
      describing the distance between spherical centers. The derivatives of the
      scattering matrix elements can be used to calculate the changes in ellipsometric
      light scattering, allowing for sensitivity and precision in quantitative models
      of fluctuations in core-shell systems. Computed results giving model contrast for
      a variety of sizes and fluctuation modes are used to design and guide novel light
      scattering experiments currently underway.

PMID- 23004907
TI  - Recognition of stable distribution with Levy index alpha close to 2.
AB  - We address the problem of recognizing alpha-stable Levy distribution with Levy
      index close to 2 from experimental data. We are interested in the case when the
      sample size of available data is not large, thus the power law asymptotics of the
      distribution is not clearly detectable, and the shape of the empirical
      probability density function is close to a Gaussian. We propose a testing
      procedure combining a simple visual test based on empirical fourth moment with
      the Anderson-Darling and Jarque-Bera statistical tests and we check the
      efficiency of the method on simulated data. Furthermore, we apply our method to
      the analysis of turbulent plasma density and potential fluctuations measured in
      the stellarator-type fusion device and demonstrate that the phenomenon of the L-H
      transition from low confinement, L mode, to a high confinement, H mode, which
      occurs in this device is accompanied by the transition from Levy to Gaussian
      fluctuation statistics.

PMID- 23004908
TI  - Wave-packet spreading dynamics under a noninstantaneous nonlinearity: self
      trapping, defocusing, and focusing.
AB  - Special localized wave modes show up in several physical scenarios including BEC
      in optical lattices, nonlinear photonic crystals, and systems with strong
      electron-phonon interaction. These result from an underlying nonlinear
      contribution to the wave equation that is usually assumed to be instantaneous.
      Here we demonstrate that the relaxation process of the nonlinearity has a
      profound impact in the wave-packet dynamics and in the formation of localized
      modes. We illustrate this phenomenology by considering the one-electron wave
      packet spreading in a C60 buckball structure whose dynamics is governed by a
      discrete nonlinear Schrodinger equation with a Debye relaxation of the
      nonlinearity. We report the full phase diagram related to the spacial extension
      of the asymptotic wave packet and unveil a complex wave-packet dynamical
      behavior.

PMID- 23004909
TI  - Mobius transformations and electronic transport properties of large disorderless
      networks.
AB  - We show that the key transport states, insulating and conducting, of large
      regular networks of scatterers can be described generically by negative and zero
      Lyapunov exponents, respectively, of Mobius maps that relate the scattering
      matrix of systems with successive sizes. The conductive phase is represented by
      weakly chaotic attractors that have been linked with anomalous transport and
      ergodicity breaking. Our conclusions, verified for serial as well as parallel
      stub and ring structures, reveal that mesoscopic behavior results from a drastic
      reduction of degrees of freedom.

PMID- 23004910
TI  - Delay-induced synchrony in complex networks with conjugate coupling.
AB  - We demonstrate stable synchronous chaos in a delay coupled network of time
      continuous dynamical system using the framework of master stability formalism
      (MSF). It is further shown that conjugate coupling, i.e., coupling using
      dissimilar variables, can substitute delay coupling of similar variables in
      retrieving delay-induced phenomena. By exploiting the MSF, we show that delayed
      conjugate coupling in an arbitrary network is capable of both inducing
      synchronization where there is no synchronization at all and enhancing
      synchronization to a large parameter space, which even the conjugate coupling
      without delay is incapable of. The above results are demonstrated using the
      paradigmatic Rossler system and Hindmarsh-Rose neuron.

PMID- 23004911
TI  - Amplitude death with mean-field diffusion.
AB  - We study the dynamics of nonlinear oscillators under mean-field diffusive
      coupling. We observe that this form of coupling leads to amplitude death via a
      synchronization transition in the parameter space of the coupling strength and
      mean-field control parameter. A general criterion for amplitude death for any
      given dynamical system with mean-field diffusion is obtained, and these dynamical
      transitions are characterized using various indices such as average phase
      difference, Lyapunov exponents, and average amplitude. This behavior is analyzed
      in the parameter plane by numerical studies of specific cases of the Landau
      Stuart limit-cycle oscillator, and Rossler, Lorenz, FitzHugh-Nagumo excitable,
      and Chua systems.

PMID- 23004912
TI  - Matter-wave solitons with the minimum number of particles in two-dimensional
      quasiperiodic potentials.
AB  - We report results of systematic numerical studies of two-dimensional matter-wave
      soliton families supported by an external potential, in a vicinity of the
      junction between stable and unstable branches of the families, where the norm of
      the solution attains a minimum, facilitating the creation of the soliton. The
      model is based on the Gross-Pitaevskii equation for the self-attractive
      condensate loaded into a quasiperiodic (QP) optical lattice (OL). The same model
      applies to spatial optical solitons in QP photonic crystals. Dynamical properties
      and stability of the solitons are analyzed with respect to variations of the
      depth and wave number of the OL. In particular, it is found that the single-peak
      solitons are stable or not in exact accordance with the Vakhitov-Kolokolov (VK)
      criterion, while double-peak solitons, which are found if the OL wave number is
      small enough, are always unstable against splitting.

PMID- 23004913
TI  - Vibrational spectra of water solutions of azoles from QM/MM calculations: effects
      of solvation.
AB  - Using microsolvation models and mixed quantum/classical ab initio molecular
      dynamics simulations, we investigate the vibrational properties of two azoles in
      water solution: pyrazole and oxazole. The effects of the water-azole hydrogen
      bonding are rationalized by an extensive comparison between structural parameters
      and harmonic frequencies obtained by microsolvation models. Following the
      effective normal-mode analysis introduced by Martinez et al. [Martinez et al., J.
      Chem. Phys. 2006, 125, 144106], we identify the vibrational frequencies of the
      solutes using the decomposition of the vibrational density of states of the gas
      phase and solution dynamics. The calculated shifts from gas phase to solution are
      fairly in agreement with the available experimental data.

PMID- 23004914
TI  - Synthesis and magnetic properties of a new family of macrocyclic M(II)3Ln(III)
      complexes: insights into the effect of subtle chemical modification on single
      molecule magnet behavior.
AB  - Thirteen tetranuclear mixed-metal complexes of the hexaimine macrocycle (L(Pr))(6
      ) have been prepared in a one-pot 3:1:3:3 reaction of copper(II) acetate hydrate,
      the appropriate lanthanide(III) nitrate hydrate, 1,4-diformyl-2,3
      dihydroxybenzene (1), and 1,3-diaminopropane. The resulting family of copper(II)
      lanthanide(III) macrocyclic complexes has the general formula
      Cu(II)(3)Ln(III)(L(Pr))(NO(3))(3).solvents (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Dy,
      Tb, Ho, Er, Tm, or Yb). X-ray crystal structure determinations carried out on
      [Cu(3)Ce(L(Pr))(NO(3))(3)(MeOH)(3)] and [Cu(3)Dy(L(Pr))(NO(3))(3)(MeOH)(3)]
      confirmed that the large Ln(III) ion is bound in the central O(6) site and the
      three square pyramidal Cu(II) ions in the outer N(2)O(2) sites (apical donor
      either nitrate anion or methanol molecule) of the Schiff base macrocycle. Only
      the structurally characterized Cu(3)Tb complex, reported earlier, is a single
      molecule magnet (SMM): the other 12 complexes do not exhibit an out-of-phase ac
      susceptibility signal or hysteresis of magnetization in a dc field. Ab initio
      calculations allowed us to rationalize the observed magnetic properties,
      including the significant impact of subtle chemical modification on SMM behavior.
      Broken-symmetry density functional theory (BS-DFT) calculations show there is a
      subtle structural balance as to whether the Cu...Cu exchange coupling is ferro-
      or antiferromagnetic. Of the family of 13 magnetically characterized tetranuclear
      Cu(II)(3)Ln(III) macrocyclic complexes prepared, only the Tb(III) complex is an
      SMM: the theoretical reasons for this are discussed.

PMID- 23004915
TI  - Molecular insights into glycogen alpha-particle formation.
AB  - Glycogen, a hyperbranched complex glucose polymer, is an intracellular glucose
      store that provides energy for cellular functions, with liver glycogen involved
      in blood-glucose regulation. Liver glycogen comprises complex alpha particles
      made up of smaller beta particles. The recent discovery that these alpha
      particles are smaller and fewer in diabetic, compared with healthy, mice
      highlights the need to elucidate the nature of alpha-particle formation; this
      paper tests various possibilities for binding within alpha particles. Acid
      hydrolysis effects, examined using dynamic light scattering and size exclusion
      chromatography, showed that the binding is not simple alpha-(1->4) or alpha-(1
      >6) glycosidic linkages. There was no significant change in alpha particle size
      after the addition of various reagents, which disrupt disulfide, protein, and
      hydrogen bonds and hydrophobic interactions. The results are consistent with
      proteinaceous binding between beta particles in alpha particles, with the
      inability of protease to break apart particles being attributed to steric
      hindrance.

PMID- 23004916
TI  - Different patterns of statin use in patients with acute myocardial infarction.
AB  - BACKGROUND/OBJECTIVE: Statins have well-established cardiovascular benefits, and
      recent evidence suggests that discontinuing statin therapy after acute myocardial
      infarction (AMI) is harmful. Our objective was to assess the association between
      statin discontinuation post-AMI and 1-year all-cause mortality in a real world
      setting. METHODS: Data on survivors of AMI between 2000 and 2007 were extracted
      from the hospital discharge summary database of Quebec and the provincial
      physician and drug claims database. Statin prescription filling was used to
      establish cohort groups. Previous statin use was defined as having filled a
      statin prescription in the 90 days pre-AMI, while post-AMI statin use was filling
      a prescription between discharge from hospital post-AMI and 90 days post
      discharge. AMI patients who survived 90 days (n=48,229) were divided into 4
      groups: i) non-users (n=11,657), did not receive statins pre- or post- AMI
      (reference group), ii) starters (n=22,452), received statins only post-AMI, iii)
      stoppers (n=488), received statins pre- but not post-AMI, and, iv) users
      (n=13,632), received statins pre- and post-AMI. Cox proportional hazards models
      were used to calculate hazard ratios (HR). RESULTS: Compared with non-users,
      stoppers had increased 1-year all-cause mortality (adjusted HR 1.36; 95% CI 1.08-
      1.70, P=0.008). Starters (HR 0.65; 95% CI 0.59-0.71, P<0.0001) and users (HR
      0.81; 95% CI 0.74-0.88, P<0.0001) had lower mortality than non-users. CONCLUSION:
      Discontinuation of statins in survivors of AMI was associated with an increase in
      1-year all-cause mortality. Physicians should use caution when discontinuing
      statins post-AMI.

PMID- 23004917
TI  - What goes around comes around: revisiting the hypothesized vicious cycle of
      dental fear and avoidance.
AB  - OBJECTIVES: A vicious cycle is believed to operate in the maintenance of dental
      fear, whereby greater dental fear leads to the delay or avoidance of dental
      visiting, deteriorated oral health and problem-oriented treatment, which then
      serves to reinforce the fear. The current study sought to uncover the existence
      of this vicious cycle pattern and to investigate the role of both dental fear and
      avoidance in terms of their hypothesized effect on treatment needs and visiting
      for problems. METHODS: Study participants were 1036 (response rate = 71.6%)
      dentate Australians (aged 15+) from all Australian states and territories.
      RESULTS: Dental fear was associated with avoidance, treatment need and problem
      oriented visiting. For people with moderate to high dental fear, 38.5% fit the
      hypothesized vicious cycle pattern of avoiding dental visiting because of fear,
      having treatment need and visiting for a problem. This compared with only 0.9% of
      people with no dental fear. Avoiding going to the dentist was an important
      predictor of treatment need and problem-oriented visiting independent of dental
      fear. Dental fear was a statistically significant predictor of treatment need and
      problem-oriented visiting and also acted as an effect modifier on avoidance
      because of fear. CONCLUSION: The results support the premises underlying the
      vicious cycle model of dental fear maintenance. Dental fear appears to act as a
      determinant of avoiding or delaying dental visit, which has flow-on effects in
      terms of greater treatment need and problem-oriented visiting.

PMID- 23004919
TI  - Identification of multitarget activity ridges in high-dimensional bioactivity
      spaces.
AB  - An activity cliff is defined as a pair of structurally similar compounds that
      have a large difference in potency against a given target. The activity cliff
      concept has recently been extended in different ways, including the introduction
      of the activity ridge data structure. An activity ridge consists of two subsets
      of highly and weakly potent structurally analogous compounds that form all
      possible pairwise activity cliffs between them. As such, the activity ridge data
      structure is rich in structure-activity relationship (SAR) information and
      attractive for SAR analysis. Activity ridges have been detected in various
      compound data sets. Analogously to single-target activity cliffs, activity rides
      have thus far only been investigated for individual targets. In this study, we
      have asked the question whether multitarget activity ridges might also exist. The
      analysis has been complicated by the limited availability of suitable compound
      profiling data sets in the public domain. However, in a high-dimensional kinase
      inhibitor data set recently released by Abbott Laboratories, multitarget activity
      ridges involving up to 43 different inhibitors and 26 kinase targets were
      identified. Given the inherently complex architecture of multitarget activity
      ridges, a new representation format was designed for these ridges based on a
      scaffold-target matrix. Furthermore, a scoring scheme was developed to identify
      compounds that were most variably distributed across a multitarget ridge and
      displayed target differentiation potential. Taken together, our results indicate
      that multitarget activity ridges represent an attractive data structure for SAR
      exploration of high-dimensional activity spaces.

PMID- 23004920
TI  - Radiation-induced human endogenous retrovirus (HERV)-R env gene expression by
      epigenetic control.
AB  - It is commonly accepted that ionizing radiation induces genomic instability by
      changes in genomic structure, epigenetic regulation and gene expression. Human
      endogenous retroviruses (HERV)-R also are often differentially expressed between
      normal and disease tissues under unstable genomic conditions and are implicated
      in the pathogenesis of several human diseases. To understand the influence of
      ionizing radiation on HERV-R expression, we performed quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) analyses using gamma-irradiated
      normal human cells. Compared to nonirradiated cells, HERV-R expression was up
      regulated in gamma-irradiated cells. The regulatory mechanism of HERV-R
      expression in irradiated cells was investigated by methylation analyses of HERV-R
      5'LTRs and treatment with garcinol. These data indicated that the up-regulated
      transcription of HERV-R may be regulated by radiation-induced epigenetic changes
      induced by histone modification, and thus could be of great importance for
      understanding the relationship between radiation-induced biological effects and
      transposable elements.

PMID- 23004921
TI  - The effect of transcutaneous electrical nerve stimulation on blood pressure.

PMID- 23004922
TI  - Chronotherapy with low-dose aspirin for prevention of complications in pregnancy.
AB  - Preeclampsia and gestational hypertension are major contributors to perinatal
      morbidity and mortality. Several studies aimed to test the effects of low-dose
      aspirin (ASA) in the prevention of preeclampsia concluded that the beneficial
      effects of such treatment outweigh adverse ones. Such benefits have not been
      fully corroborated by larger randomized trials usually carried out in low-risk
      women, testing a dose of 60 mg/d ASA presumably ingested in the morning, and
      including women randomized as late as at 26-32 wks of gestation. The authors
      conducted a prospective, randomized, double-blind, placebo-controlled,
      chronotherapy trial on 350 high-risk pregnant women (183 nulliparous), 30.7 +/-
      5.3 (mean +/- SD) yrs of age, and 13.5 +/- 1.4 wks of gestation at the time of
      recruitment. Women were randomly assigned to one of six groups, defined according
      to treatment (placebo or ASA, 100 mg/d) and time of treatment: upon awakening, 8
      h after awakening, or at bedtime. Intervention started at 12-16 wks of gestation
      and continued until delivery. Blood pressure (BP) was measured by ambulatory
      monitoring (ABPM) for 48-h at baseline, every 4 wks until the 7th month of
      gestation, every 2 wks thereafter until delivery, and at puerperium. The effects
      of ASA on ambulatory BP were markedly dependent on administration time: there was
      no effect on BP, compared with placebo, when ASA was ingested upon awakening, but
      the BP reduction was highly statistically significant when low-dose ASA was
      ingested 8 h after awakening and, to a greater extent, at bedtime (p < .001). At
      puerperium, 6-8 wks after discontinuation of treatment, there was no
      statistically significant difference in 24-h BP means between the groups of women
      who ingested ASA at different circadian times. Women ingesting low-dose ASA,
      compared with placebo, evidenced a significantly lower hazard ratio (HR) of
      serious adverse outcomes, a composite of preeclampsia, preterm delivery,
      intrauterine growth retardation (IUGR), and stillbirth (.35, 95% confidence
      interval [CI]: .22-.56; p < .001). The HR of individual outcome variables, i.e.,
      preeclampsia, preterm delivery, IUGR, and gestational hypertension, were also
      significantly lower with ASA versus placebo (p always < .041). There were small
      and nonsignificant differences in outcomes between placebo and low-dose ASA
      ingested upon awakening. These four groups combined showed highly significant
      greater event rate of serious adverse outcomes than women ingesting ASA either in
      the evening or at bedtime (HR: .19, 95% CI: .10-.39; p < .001). There was no
      increased risk of hemorrhage, either before or after delivery, with low-dose ASA
      relative to placebo (HR: .57, 95% CI: .25-1.33; p = .194). Results indicate that
      (i) 100 mg/d ASA should be the recommended minimum dose for prevention of
      complications in pregnancy; (ii) ingestion of low-dose ASA should start at <=16
      wks of gestation; and (iii) low-dose ASA ingested at bedtime, but not upon
      awakening, significantly regulates ambulatory BP and reduces the incidence of
      preeclampsia, gestational hypertension, preterm delivery, and IUGR. ABPM
      evaluation at the first trimester of pregnancy provides sensitive endpoints for
      identification of women at high risk for preeclampsia who might benefit most from
      the cost-effective preventive intervention with timed low-dose ASA.

PMID- 23004924
TI  - The impact of the economic downturn and health care reform on treatment decisions
      for haemophilia A: patient, caregiver and health care provider perspectives.
AB  - Little is known about the impact of the recent US economic downturn and health
      care reform on patient, caregiver and health care provider (HCP) decision-making
      for haemophilia A. To explore the impact of the recent economic downturn and
      perceived impact of health care reform on haemophilia A treatment decisions from
      patient, caregiver and HCP perspectives. Patients/caregivers and HCPs completed a
      self-administered survey in 2011. Survey participants were asked about
      demographics, the impact of the recent economic downturn and health care reform
      provisions on their treatment decisions. Seventy three of the 134 (54%)
      patients/caregivers and 39 of 48 (81%) HCPs indicated that the economic downturn
      negatively impacted haemophilia care. Seventy of the 73 negatively impacted
      patients made financially related treatment modifications, including
      delaying/cancelling routine health care visit, skipping doses and/or skipping
      filling prescription. Treatment modifications made by HCPs included delaying
      elective surgery, switching from higher to lower priced product, switching from
      recombinant to plasma-derived products and delaying prophylaxis. Health care
      reform was generally perceived as positive. Due to the elimination of lifetime
      caps, 30 of 134 patients (22%) and 28 of 48 HCPs (58%) indicated that they will
      make treatment modifications by initiating prophylaxis or scheduling routine
      appointment/surgery sooner. Both patients/caregivers and HCPs reported that the
      economic downturn had a negative impact on haemophilia A treatment. Suboptimal
      treatment modifications were made due to the economic downturn. Health care
      reform, especially the elimination of lifetime caps, was perceived as positive
      for haemophilia A treatment and as a potential avenue for contributing to more
      optimal treatment behaviours.

PMID- 23004925
TI  - Cutaneous leukocytoclastic vasculitis due to Salmonella enteritidis in a child
      with interleukin-12 receptor beta-1 deficiency.
AB  - Defects in the interleukin 12 (IL-12)/interferon gamma (IFN-gamma) pathway result
      in Mendelian susceptibility to mycobacterial disease (MSMD). IL-12 receptor beta
      1 (IL-12Rbeta1) deficiency, the most common form of MSMD, is associated with
      weakly virulent mycobacteria and salmonella. Infections in patients with this
      deficiency are extraintestinal, or septicemic, recurrent infections with
      nontyphoid salmonellae. Here we report a case of an IL-12Rbeta1 deficiency with
      cutaneous leukocytoclastic vasculitis due to Salmonella enteritidis. 

PMID- 23004926
TI  - Efficacy and safety of methantheline bromide (Vagantin((r)) ) in axillary and
      palmar hyperhidrosis: results from a multicenter, randomized, placebo-controlled
      trial.
AB  - BACKGROUND: Focal hyperhidrosis can severely affect quality of life. So far,
      knowledge on the effect of systemic therapy of focal hyperhidrosis is limited.
      OBJECTIVE: To assess the efficacy and safety of methantheline bromide (MB) in the
      treatment of axillary and palmar-axillary hyperhidrosis. METHODS: A multicenter
      controlled randomized double-blind clinical trial was conducted in patients with
      axillary or palmar-axillary hyperhidrosis defined by a sweat production >50 mg/5
      min. Patients received 3 * 50 mg MB daily or placebo over a period of 28 +/- 1
      days. Main outcome criterion was the reduction of sweat as measured by gravimetry
      on day 28 +/- 1. Quality of life was assessed by Dermatology Life Quality Index
      (DLQI) and Hyperhidrosis Disease Severity Score (HDSS). RESULTS: A total of 339
      patients were randomly assigned to receive MB or placebo. On day 28 +/- 1, the
      mean axillary sweat production was 99 mg for MB and 130 mg for placebo compared
      with 168 mg and 161 mg respectively at baseline (P = 0.004). Patient's HDSS score
      decreased in the MB group from 3.2 to 2.4 compared with 3.2 to 2.7 for placebo (P
      = 0.002). Similar results could be obtained for the DLQI with 9.7 for MB and 12.2
      for placebo, which decreased from 16.4 or 17 respectively (P = 0.003).
      Tolerability was good for both groups. The most frequent adverse event was dry
      mouth. CONCLUSION: Fifty milligrams methantheline bromide three times a day is an
      effective and safe treatment of axillary hyperhidrosis.

PMID- 23004927
TI  - Immediate renal transplantation after radical prostatectomy for low-risk prostate
      cancer.
AB  - INTRODUCTION: For most cancers, a two- to five-yr period with no evidence of
      disease must be demonstrated before organ transplantation. The natural history of
      prostate cancer is unique both because of extensive pre-treatment screening and
      the ease of post-treatment monitoring for recurrence. Using available predictive
      models for prostate cancer recurrence, we examine whether current evidence
      supports a prolonged waiting period after radical prostatectomy and before renal
      transplantation. MATERIALS AND METHODS: A MedLine search was conducted to
      identify five series (published between 2000 and 2011), which examined
      biochemical recurrence (BCR) after prostatectomy for low-risk prostate cancer.
      The likelihood of BCR at one, two, and five yr after radical prostatectomy was
      identified for each series. RESULTS: Each of the analyzed series demonstrated
      that the likelihood of BCR after radical prostatectomy for low-risk prostate
      cancer was identical at one, two, and five yr and did not exceed 5%. CONCLUSIONS:
      The likelihood of BCR does not increase during the first five yr after radical
      prostatectomy for low-risk prostate cancer. Additionally, the risk of recurrence
      approaches zero during this period. Therefore, current evidence does not support
      the mandated waiting period of five yr before organ transplantation.

PMID- 23004928
TI  - The contributions of human factors and ergonomics to a sustainable minerals
      industry.
AB  - This article describes examples of the application of human factors research and
      development work to a sustainable minerals industry. It begins by outlining human
      related aspects of the minerals industry and the key human factors work
      previously undertaken in this domain. The focus then switches to sustainability
      in the minerals industry. Sustainability principles are introduced and
      illustrations provided of how human factors research and development work fits
      within such a framework. Three case studies of human factors in the minerals
      industry research are presented and the sustainability implications in each case
      study are highlighted. Finally, future trends related to human factors work in a
      sustainable minerals industry are addressed, in particular the opportunities and
      possible adverse consequences that increasing deployment of mining automation
      might bring. PRACTITIONER SUMMARY: Minerals industries are a major global
      activity with significant sustainability implications. Aspects of sustainability
      in mining are examined using three case studies. These illustrate the
      contribution of human factors/ergonomics in reducing risks; developing emergency
      response management systems; and the value of participatory ergonomics in
      improving the design of mining equipment.

PMID- 23004929
TI  - Preclinical antitumor activity of thiarabine in human leukemia and lymphoma
      xenograft models.
AB  - Thiarabine was evaluated for antitumor activity in seven human leukemia,
      lymphoma, and myeloma xenograft models to explore the activity in hematological
      malignancies. Thiarabine was active against all of the human leukemia and
      lymphoma lines tested, being curative against HL-60 leukemia and AS283 lymphoma
      and effecting tumor regressions in CCRF-CEM, MOLT-4, and K-562 leukemia and RL
      lymphoma models, but did not exhibit any appreciable activity against RPMI-8226
      myeloma. For the leukemia/lymphoma models, thiarabine was more efficacious than
      ara-C/palmO-ara-C (four models), clofarabine (three models), fludarabine
      monophosphate (five models), cladribine (four models), and gemcitabine (six
      models). Thiarabine warrants future clinical trials with leukemias/lymphomas.

PMID- 23004930
TI  - Synthesis and properties of DNA containing cyclonucleosides.
AB  - Here, we present efficient syntheses of the R and S diastereomers of 8,5'-cyclo
      2'-deoxyadenosine and 6,5'-cyclo-2'-deoxyuridine. We incorporated these
      interesting nucleosides into DNA to study how the cyclo linkage affects the
      stability of duplex formation.

PMID- 23004931
TI  - Study and synthesis of biologically active phenothiazines, their sulfones, and
      ribofuranosides.
AB  - The present article describes the synthesis of new 10H-phenothiazines using the
      Smiles rearrangement. These synthesized phenothiazines on oxidation with 30%
      hydrogen peroxide in glacial acetic acid yield sulfones, and when treated with
      sugar give ribofuranosides. These compounds are evaluated for their anthelmintic
      and antimicrobial activities. The structural assignment of the synthesized
      compounds is made on the basis of elemental analysis and spectroscopic data.

PMID- 23004932
TI  - Preclinical combination therapy of clofarabine plus radiation.
AB  - Clofarabine, an approved anticancer drug, was evaluated in combination with
      radiation in six subcutaneously implanted human tumor xenograft models.
      Clofarabine had no effect on the growth of SF-295 glioblastoma, which was not
      enhanced by radiation. There was no difference between clofarabine with and
      without radiation in the DU-145 prostate model. The combined effect on NCI-H460
      lung tumors appeared to be additive. SR475 head and neck, PANC-1 pancreatic, and
      HCT-116 colon tumors were radiomodified by clofarabine. The radiomodifying
      capacity of clofarabine was superior to that for gemcitabine in two models (PANC
      1 and HCT-116) and was comparable in the other four models.

PMID- 23004933
TI  - An ab initio investigation of fluorobromo carbene.
AB  - Fluorobromo carbene, an important halogenated carbene in the stratospheric ozone
      depletion, has long been received considerable interest. However, the energy,
      structure, and dynamics of even the lowest excited states have not been well
      understood. In this paper, we performed a detail ab initio study on CFBr using
      complete active space second-order perturbation (CASPT2) and multireference
      configuration interaction (MRCI) method. We investigated the effect of basis set
      on the CASPT2 results of the ground X(1)A' state and the first excited singlet
      A(1)A" state. The potential energy surface (PES) of the A(1)A" state along C-Br
      bond distance was carefully examined at CASPT2/cc-pV5Z level, by optimizing C-F
      bond and F-C-Br angle at every C-Br bond length in contrast to fix them at the
      equilibrium values. On the basis of the PES, a reliable barrier height of the
      A(1)A" state was obtained from CASPT2 and MRCI+Q calculations with different
      basis sets, considering the scalar relativistic effect, spin-orbit coupling, and
      core-valence correlation. Finally, we carried out the first theoretical study on
      higher excited state with energy up to 7 eV. The present calculated results were
      compared with previous experimental and theoretical results where available. Our
      results will add some understanding and shed more light on the structure and
      dynamics of electronic states of CFBr radical.

PMID- 23004934
TI  - Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine
      phenotype and predicts the development and severity of infant allergic disease.
AB  - BACKGROUND: Previous studies have demonstrated that reduced T-cell protein kinase
      C zeta (PKCzeta) expression is associated with allergy development in infants
      born to atopic mothers. This study examined whether this relationship extends to
      a general population and addressed the basis for the association. METHODS: A flow
      cytometry assay was developed for the measurement of T-cell PKCzeta levels in
      PBMC, cord blood mononuclear cell and whole blood. Cord blood T-cell PKCzeta
      levels were measured in 135 neonates, and allergic disease was evaluated by skin
      prick test and clinical examination at 12 months of age. RESULTS: Allergic
      children (particularly those with eczema) had significantly lower neonatal T-cell
      PKCzeta expression than nonallergic children (P < 0.001). PKCzeta levels
      predicted allergic disease with optimal specificity of 86% and sensitivity of
      54%. The sensitivity was increased in the children of allergic mothers, who had
      significantly lower PKC levels than the children of nonallergic mothers. Cord
      blood PKCzeta levels did not affect T-cell maturation in culture as assessed by
      CD45RA/RO expression, but low PKCzeta expression was associated with reduced
      capacity for IFNgamma production by matured T cells. Low cord blood PKC
      expression was further associated with increased IL-13 responses at 6 months.
      CONCLUSIONS: The findings suggest a potential role for the use of PKCzeta levels
      in cord blood T cells as a presymptomatic test to predict allergy risk in
      children, particularly offspring of allergic mothers, and that the basis of this
      relationship is related to cytokine patterns in mature T cells.

PMID- 23004936
TI  - Spin-transfer pathways in paramagnetic lithium transition-metal phosphates from
      combined broadband isotropic solid-state MAS NMR spectroscopy and DFT
      calculations.
AB  - Substituted lithium transition-metal (TM) phosphate LiFe(x)Mn(1-x)PO(4) materials
      with olivine-type structures are among the most promising next generation lithium
      ion battery cathodes. However, a complete atomic-level description of the
      structure of such phases is not yet available. Here, a combined experimental and
      theoretical approach to the detailed assignment of the (31)P NMR spectra of the
      LiFe(x)Mn(1-x)PO(4) (x = 0, 0.25, 0.5, 0.75, 1) pure and mixed TM phosphates is
      developed and applied. Key to the present work is the development of a new NMR
      experiment enabling the characterization of complex paramagnetic materials via
      the complete separation of the individual isotropic chemical shifts, along with
      solid-state hybrid DFT calculations providing the separate hyperfine
      contributions of all distinct Mn-O-P and Fe-O-P bond pathways. The NMR
      experiment, referred to as aMAT, makes use of short high-powered adiabatic pulses
      (SHAPs), which can achieve 100% inversion over a range of isotropic shifts on the
      order of 1 MHz and with anisotropies greater than 100 kHz. In addition to
      complete spectral assignments of the mixed phases, the present study provides a
      detailed insight into the differences in electronic structure driving the
      variations in hyperfine parameters across the range of materials. A simple model
      delimiting the effects of distortions due to Mn/Fe substitution is also proposed
      and applied. The combined approach has clear future applications to TM-bearing
      battery cathode phases in particular and for the understanding of complex
      paramagnetic phases in general.

PMID- 23004935
TI  - Luteolin prevents solar radiation-induced matrix metalloproteinase-1 activation
      in human fibroblasts: a role for p38 mitogen-activated protein kinase and
      interleukin-20 released from keratinocytes.
AB  - Human skin is continuously exposed to solar radiation, which can result in
      photoaging, a process involving both dermal and, to a lesser extent, epidermal
      structures. Previously, we have shown that the flavonoid luteolin protects the
      epidermis from ultraviolet (UV)-induced damage by a combination of UV-absorbing,
      antioxidant, and antiinflammatory properties. The aim of the present study was to
      determine direct and indirect effects of luteolin on dermal fibroblasts as major
      targets of photoaging. Stimulation of fibroblasts with UVA light or the
      proinflammatory cytokine interleukin-20 (IL-20) is associated with wrinkled skin,
      increased IL-6 secretion, matrix metalloproteinase (MMP-1) expression, and
      hyaluronidase activity. All of these targets were inhibited by luteolin via
      interference with the p38 mitogen-activated protein kinase (MAPK) pathway. Next,
      we assessed the role of conditioned supernatants from keratinocytes irradiated
      with solar-simulated radiation (SSR) on nonirradiated dermal fibroblasts. In
      keratinocytes, luteolin inhibited SSR-induced production of IL-20, also via
      interference with the p38 MAPK pathway. Similarly, keratinocyte supernatant
      induced IL-6 and MMP-1 expression in fibroblasts was reduced by pretreatment of
      keratinocytes with luteolin. Finally, these results were confirmed ex vivo on
      skin explants treated with luteolin before UV irradiation. Our results suggest
      that SSR-mediated production of soluble factors in keratinocytes is modulated by
      luteolin and may attenuate photoaging in dermal fibroblasts.

PMID- 23004937
TI  - Imaging and monitoring sleep and its disorders: local sleep, circadian rhythms
      and variability.

PMID- 23004939
TI  - Violation of the Cauchy-Schwarz inequality with matter waves.
AB  - The Cauchy-Schwarz (CS) inequality-one of the most widely used and important
      inequalities in mathematics-can be formulated as an upper bound to the strength
      of correlations between classically fluctuating quantities. Quantum-mechanical
      correlations can, however, exceed classical bounds. Here we realize four-wave
      mixing of atomic matter waves using colliding Bose-Einstein condensates, and
      demonstrate the violation of a multimode CS inequality for atom number
      correlations in opposite zones of the collision halo. The correlated atoms have
      large spatial separations and therefore open new opportunities for extending
      fundamental quantum-nonlocality tests to ensembles of massive particles.

PMID- 23004938
TI  - Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer
      and anti-angiogenic activities.
AB  - BACKGROUND AND PURPOSE: Drugs targeting microtubules are commonly used for cancer
      treatment. However, the potency of microtubule inhibitors used clinically is
      limited by the emergence of resistance. We thus designed a strategy to find new
      cell-permeable microtubule-targeting agents. EXPERIMENTAL APPROACH: Using a cell
      based assay designed to probe for microtubule polymerization status, we screened
      a chemical library and identified two azaindole derivatives, CM01 and CM02, as
      cell-permeable microtubule-depolymerizing agents. The mechanism of the anti
      tumour effects of these two compounds was further investigated both in vivo and
      in vitro. KEY RESULTS: CM01 and CM02 induced G2/M cell cycle arrest and exerted
      potent cytostatic effects on several cancer cell lines including multidrug
      resistant (MDR) cell lines. In vitro experiments revealed that the azaindole
      derivatives inhibited tubulin polymerization and competed with colchicines for
      this effect, strongly indicating that tubulin is the cellular target of these
      azaindole derivatives. In vivo experiments, using a chicken chorioallantoic
      xenograft tumour assay, established that these compounds exert a potent anti
      tumour effect. Furthermore, an assay probing the growth of vessels out of
      endothelial cell spheroids showed that CM01 and CM02 exert anti-angiogenic
      activities. CONCLUSIONS AND IMPLICATIONS: CM01 and CM02 are reversible
      microtubule-depolymerizing agents that exert potent cytostatic effects on human
      cancer cells of diverse origins, including MDR cells. They were also shown to
      inhibit angiogenesis and tumour growth in chorioallantoic breast cancer
      xenografts. Hence, these azaindole derivatives are attractive candidates for
      further preclinical investigations.

PMID- 23004940
TI  - Universal equation of state of a unitary fermionic gas.
AB  - It is suggested that for a Fermi gas at unitarity, the two-body bond plays a
      special role. We propose an equation of state using an ansatz relating the
      interaction part of the l-body cluster to its two-body counterpart. This allows a
      parameter-free comparison with the recently measured equation of state by the ENS
      group. The agreement between the two over a range of fugacity (z<5 for a
      homogeneous gas, and z<10 for the trapped gas) leads us to perform the
      calculations of more sensitive quantities measured recently by the MIT group.

PMID- 23004941
TI  - Nonclassicality criteria from phase-space representations and information
      theoretical constraints are maximally inequivalent.
AB  - We consider two celebrated criteria for defining the nonclassicality of bipartite
      bosonic quantum systems, the first stemming from information theoretic concepts
      and the second from physical constraints on the quantum phase space.
      Consequently, two sets of allegedly classical states are singled out: (i) the set
      C composed of the so-called classical-classical (CC) states-separable states that
      are locally distinguishable and do not possess quantum discord; (ii) the set P of
      states endowed with a positive P representation (P-classical states)-mixtures of
      Glauber coherent states that, e.g., fail to show negativity of their Wigner
      function. By showing that C and P are almost disjoint, we prove that the two
      defining criteria are maximally inequivalent. Thus, the notions of classicality
      that they put forward are radically different. In particular, generic CC states
      show quantumness in their P representation, and vice versa, almost all P
      classical states have positive quantum discord and, hence, are not CC. This
      inequivalence is further elucidated considering different applications of P
      classical and CC states. Our results suggest that there are other quantum
      correlations in nature than those revealed by entanglement and quantum discord.

PMID- 23004943
TI  - Quantum measurement bounds beyond the uncertainty relations.
AB  - In quantum mechanics, the Heisenberg uncertainty relations and the Cramer-Rao
      inequalities typically limit the precision in the estimation of a parameter
      through the standard deviation of a conjugate observable. Here we extend these
      relations by giving a bound to the precision of a parameter in terms of the
      expectation value of the conjugate observable. This has both foundational and
      practical consequences: in quantum optics it resolves a controversy over which is
      the ultimate precision in interferometry.

PMID- 23004942
TI  - Implications of the Pusey-Barrett-Rudolph quantum no-go theorem.
AB  - Pusey, Barrett, and Rudolph introduce a new no-go theorem for hidden-variables
      models of quantum theory. We make precise the class of models targeted and
      construct equivalent models that evade the theorem. The theorem requires
      assumptions for models of composite systems, which we examine, determining
      compactness as the weakest assumption needed. On that basis, we demonstrate
      results of the Bell-Kochen-Specker theorem. Given compactness and the relevant
      class of models, the theorem can be seen as showing that some measurements on
      composite systems must have built-in inefficiencies, complicating its testing.

PMID- 23004944
TI  - Quantum measurement occurrence is undecidable.
AB  - In this work, we show that very natural, apparently simple problems in quantum
      measurement theory can be undecidable even if their classical analogues are
      decidable. Undecidability hence appears as a genuine quantum property here.
      Formally, an undecidable problem is a decision problem for which one cannot
      construct a single algorithm that will always provide a correct answer in finite
      time. The problem we consider is to determine whether sequentially used identical
      Stern-Gerlach-type measurement devices, giving rise to a tree of possible
      outcomes, have outcomes that never occur. Finally, we point out implications for
      measurement-based quantum computing and studies of quantum many-body models and
      suggest that a plethora of problems may indeed be undecidable.

PMID- 23004945
TI  - Multipartite entanglement verification resistant against dishonest parties.
AB  - Future quantum information networks will consist of quantum and classical agents,
      who have the ability to communicate in a variety of ways with trusted and
      untrusted parties and securely delegate computational tasks to untrusted large
      scale quantum computing servers. Multipartite quantum entanglement is a
      fundamental resource for such a network and, hence, it is imperative to study the
      possibility of verifying a multipartite entanglement source in a way that is
      efficient and provides strong guarantees even in the presence of multiple
      dishonest parties. In this Letter, we show how an agent of a quantum network can
      perform a distributed verification of a source creating multipartite Greenberger
      Horne-Zeilinger (GHZ) states with minimal resources, which is, nevertheless,
      resistant against any number of dishonest parties. Moreover, we provide a tight
      tradeoff between the level of security and the distance between the state
      produced by the source and the ideal GHZ state. Last, by adding the resource of a
      trusted common random source, we can further provide security guarantees for all
      honest parties in the quantum network simultaneously.

PMID- 23004946
TI  - Randomized benchmarking of multiqubit gates.
AB  - We describe an extension of single-qubit gate randomized benchmarking that
      measures the error of multiqubit gates in a quantum information processor. This
      platform-independent protocol evaluates the performance of Clifford unitaries,
      which form a basis of fault-tolerant quantum computing. We implemented the
      benchmarking protocol with trapped ions and found an error per random two-qubit
      Clifford unitary of 0.162+/-0.008, thus setting the first benchmark for such
      unitaries. By implementing a second set of sequences with an extra two-qubit
      phase gate inserted after each step, we extracted an error per phase gate of
      0.069+/-0.017. We conducted these experiments with transported, sympathetically
      cooled ions in a multizone Paul trap-a system that can in principle be scaled to
      larger numbers of ions.

PMID- 23004947
TI  - From Majorana fermions to topological order.
AB  - We consider a system consisting of a 2D network of links between Majorana
      fermions on superconducting islands. We show that the fermionic Hamiltonian
      modeling this system is topologically ordered in a region of parameter space: we
      show that Kitaev's toric code emerges in fourth-order perturbation theory. By
      using a Jordan-Wigner transformation we can map the model onto a family of signed
      2D Ising models in a transverse field where the signs, ferromagnetic or
      antiferromagnetic, are determined by additional gauge bits. Our mapping allows an
      understanding of the nonperturbative regime and the phase transition to a
      nontopological phase. We discuss the physics behind a possible implementation of
      this model and argue how it can be used for topological quantum computation by
      adiabatic changes in the Hamiltonian.

PMID- 23004948
TI  - Observation of quantum interference as a function of Berry's phase in a complex
      Hadamard optical network.
AB  - Emerging models of quantum computation driven by multiphoton quantum
      interference, while not universal, may offer an exponential advantage over
      classical computers for certain problems. Implementing these circuits via
      geometric phase gates could mitigate requirements for error correction to achieve
      fault tolerance while retaining their relative physical simplicity. We report an
      experiment in which a geometric phase is embedded in an optical network with no
      closed loops, enabling quantum interference between two photons as a function of
      the phase.

PMID- 23004949
TI  - Experimental Monte Carlo quantum process certification.
AB  - Experimental implementations of quantum information processing have now reached a
      level of sophistication where quantum process tomography is impractical. The
      number of experimental settings as well as the computational cost of the data
      postprocessing now translates to days of effort to characterize even experiments
      with as few as 8 qubits. Recently a more practical approach to determine the
      fidelity of an experimental quantum process has been proposed, where the
      experimental data are compared directly with an ideal process using Monte Carlo
      sampling. Here, we present an experimental implementation of this scheme in a
      circuit quantum electrodynamics setup to determine the fidelity of 2-qubit gates,
      such as the CPHASE and the CNOT gate, and 3-qubit gates, such as the Toffoli gate
      and two sequential CPHASE gates.

PMID- 23004950
TI  - Nonequilibrium Kondo model: crossover from weak to strong coupling.
AB  - We analyze the nonequilibrium Kondo model at finite voltage and temperature by
      using a new formulation of the real-time renormalization group method with the
      Laplace variable as the flow parameter. We evaluate the energy-dependent spin
      relaxation rate and nonlinear conductance, and derive an approximate form for the
      universal line shape for the latter in the whole crossover regime from weak to
      strong coupling. The results are shown to agree well with exact methods in
      equilibrium, Fermi-liquid theory, weak-coupling expansions, and recent
      experiments. For the transient spin dynamics we find a universal exponential
      decay in the long-time limit along with a truncation-dependent pre-exponential
      power law. For multichannel models a pure power-law decay typical for non-Fermi
      liquid behavior is predicted.

PMID- 23004951
TI  - Oscillating test of the isotropic shift of the speed of light.
AB  - In this Letter, we present an improved constraint on possible isotropic
      variations of the speed of light. Within the framework of the standard model
      extension, we provide a limit on the isotropic, scalar parameter kappa(tr) of 3+/
      11*10({-10), an improvement by a factor of 6 over previous constraints. This was
      primarily achieved by modulating the orientation of the experimental apparatus
      with respect to the velocity of Earth. This orientation modulation shifts the
      signal for Lorentz invariance to higher frequencies, and we have taken advantage
      of the higher stability of the resonator at shorter time scales, together with
      better rejection of systematic effects, to provide a new constraint.

PMID- 23004952
TI  - Filamentary diffusion of cosmic rays on small scales.
AB  - We investigate the diffusion of cosmic rays (CRs) close to their sources.
      Propagating individual CRs in purely isotropic turbulent magnetic fields with
      maximal scale of spatial variations l(max), we find that CRs diffuse
      anisotropically at distances r <=/~ l(max) from their sources. As a result, the
      CR densities around the sources are strongly irregular and show filamentary
      structures. We determine the transition time t(*) to standard diffusion as t(*) ~
      10(4) yr(l(max)/150 pc)(beta)(E/PeV)(-gamma)(B(rms)/4 MUG)(gamma), with beta =/~
      2 and gamma=0.25-0.5 for a turbulent field with a Kolmogorov power spectrum. We
      calculate the photon emission due to CR interactions with gas and the resulting
      irregular source images.

PMID- 23004953
TI  - Intermittency and local heating in the solar wind.
AB  - Evidence for nonuniform heating in the solar wind plasma near current sheets
      dynamically generated by magnetohydrodynamic (MHD) turbulence is obtained using
      measurements from the ACE spacecraft. These coherent structures only constitute
      19% of the data, but contribute 50% of the total plasma internal energy.
      Intermittent heating manifests as elevations in proton temperature near current
      sheets, resulting in regional heating and temperature enhancements extending over
      several hours. The number density of non-Gaussian structures is found to be
      proportional to the mean proton temperature and solar wind speed. These results
      suggest magnetofluid turbulence drives intermittent dissipation through a
      hierarchy of coherent structures, which collectively could be a significant
      source of coronal and solar wind heating.

PMID- 23004954
TI  - Kinetic signatures and intermittent turbulence in the solar wind plasma.
AB  - A connection between kinetic processes and intermittent turbulence is observed in
      the solar wind plasma using measurements from the Wind spacecraft at 1 A.U. In
      particular, kinetic effects such as temperature anisotropy and plasma heating are
      concentrated near coherent structures, such as current sheets, which are
      nonuniformly distributed in space. Furthermore, these coherent structures are
      preferentially found in plasma unstable to the mirror and firehose instabilities.
      The inhomogeneous heating in these regions, which is present in both the magnetic
      field parallel and perpendicular temperature components, results in protons at
      least 3-4 times hotter than under typical stable plasma conditions. These results
      offer a new understanding of kinetic processes in a turbulent regime, where
      linear Vlasov theory is not sufficient to explain the inhomogeneous plasma
      dynamics operating near non-Gaussian structures.

PMID- 23004955
TI  - Neutrino scattering and flavor transformation in supernovae.
AB  - We argue that the small fraction of neutrinos that undergo direction-changing
      scattering outside of the neutrinosphere could have significant influence on
      neutrino flavor transformation in core-collapse supernova environments. We show
      that the standard treatment for collective neutrino flavor transformation is
      adequate at late times but could be inadequate in early epochs of core-collapse
      supernovae, where the potentials that govern neutrino flavor evolution are
      affected by the scattered neutrinos. Taking account of this effect, and the way
      it couples to entropy and composition, will require a new approach in neutrino
      flavor transformation modeling.

PMID- 23004956
TI  - Decoherence and loss of entanglement in acoustic black holes.
AB  - We study the process of decoherence in acoustic black holes. We focus on the ion
      trap model proposed by Horstmann et al. [Phys. Rev. Lett. 104, 250403 (2010)],
      but the formalism is general to any experimental implementation. For that
      particular setup, we compute the decoherence time for the experimental parameters
      that they proposed. We find that a quantum to classical transition occurs during
      the measurement, and we propose improved parameters to avoid such a feature. We
      also study the entanglement between the Hawking-pair phonons for an acoustic
      black hole while in contact with a reservoir, through the quantum correlations,
      showing that they remain strongly correlated for small enough times and
      temperatures.

PMID- 23004957
TI  - Natural inflation on a steep potential with classical non-Abelian gauge fields.
AB  - We propose a model for inflation consisting of an axionic scalar field coupled to
      a set of three non-Abelian gauge fields. Our model's novel requirement is that
      the gauge fields begin inflation with a rotationally invariant vacuum expectation
      value (VEV) that is preserved through identification of SU(2) gauge invariance
      with rotations in three dimensions. The gauge VEV interacts with the background
      value of the axion, leading to an attractor solution that exhibits slow roll
      inflation even when the axion decay constant has a natural value (<M(Pl)).
      Assuming a sinusoidal potential for the axion, we find that inflation continues
      until the axionic potential vanishes. The speed at which the axion moves along
      its potential is modulated by its interactions with the gauge VEV, rather than
      being determined by the slope of its bare potential. For sub-Planckian axion
      decay constants vanishingly small tensor to scalar ratios are predicted, a direct
      consequence of the Lyth bound. The parameter that controls the interaction
      strength between the axion and the gauge fields requires a technically natural
      tuning of O(100).

PMID- 23004958
TI  - Relating direct CP violation in D decays and the forward-backward asymmetry in
      tt[over -] production.
AB  - The CDF and LHCb experiments have recently provided two intriguing hints for new
      physics: a large forward-backward asymmetry in tt[over -] production and a direct
      CP asymmetry in D decays of order of a percent. In both cases, flavor
      nonuniversal interactions are required in the up sector, raising the possibility
      that the two effects come from one and the same new physics source. We show that
      a minimal model, with an extra scalar doublet, previously suggested to explain
      the top data, gives-without any modifications or additions-a contribution to CP
      violation in charm decays that is of the right size.

PMID- 23004959
TI  - Geometric action for nongeometric fluxes.
AB  - We give a geometrical interpretation of the nongeometric Q and R fluxes. To this
      end, we consider double field theory in a formulation that is related to the
      conventional one by a field redefinition taking the form of a T duality
      inversion. The R flux is a tensor under diffeomorphisms and satisfies a
      nontrivial Bianchi identity. The Q flux can be viewed as part of a connection
      that covariantizes the winding derivatives with respect to diffeomorphisms. We
      give a higher-dimensional action with a kinetic term for the R flux and a "dual"
      Einstein-Hilbert term containing the connection Q.

PMID- 23004961
TI  - Classical limit of the three-point function of n=4 supersymmetric Yang-Mills
      theory from integrability.
AB  - We give an analytic expression for the correlation function of three large
      classical nonprotected operators in N=4 super-Yang-Mills theory at weak coupling.
      We restrict ourselves to operators belonging to an su(2) sector of the theory. In
      order to carry out the calculation, we derive, by unveiling a hidden
      factorization property, the thermodynamical limit of Slavnov's determinant.

PMID- 23004962
TI  - Total width of 125 GeV Higgs boson.
AB  - By using the LHC and Tevatron measurements of the cross sections to various decay
      channels relative to the standard model Higgs boson, the total width of the
      putative 125 GeV Higgs boson is determined as 6.1(-2.9)(+7.7) MeV. We describe a
      way to estimate the branching fraction for the Higgs-boson decay to dark matter.
      We also discuss a no-go theorem for the gammagamma signal of the Higgs boson at
      the LHC.

PMID- 23004960
TI  - Search for violation of Lorentz invariance in top quark pair production and
      decay.
AB  - Using data collected with the D0 detector at the Fermilab Tevatron Collider,
      corresponding to 5.3 fb(-1) of integrated luminosity, we search for violation of
      Lorentz invariance by examining the tt[over -] production cross section in
      lepton+jets final states. We quantify this violation using the standard-model
      extension framework, which predicts a dependence of the tt[over -] production
      cross section on sidereal time as the orientation of the detector changes with
      the rotation of the Earth. Within this framework, we measure components of the
      matrices (c(Q))(MUnu33) and (c(U))(MUnu33) containing coefficients used to
      parametrize violation of Lorentz invariance in the top quark sector. Within
      uncertainties, these coefficients are found to be consistent with zero.

PMID- 23004968
TI  - Total nucleon-nucleon cross section at large N(c).
AB  - It is shown that at sufficiently large N(c) for incident momenta which are much
      larger than the QCD scale, the total nucleon-nucleon cross section is independent
      of incident momentum and given by sigma(total)=2pilog(2)(N(c))/(m(pi)(2)). This
      result is valid in the extreme large N(c) regime of log(N(c))>>1 and has
      corrections of relative order log(log(N(c)))/log(N(c)). A possible connection of
      this result to the Froissart-Martin bound is discussed.

PMID- 23004967
TI  - Strong running coupling at tau and Z(0) mass scales from lattice QCD.
AB  - This Letter reports on the first computation, from data obtained in lattice QCD
      with u, d, s, and c quarks in the sea, of the running strong coupling via the
      ghost-gluon coupling renormalized in the momentum-subtraction Taylor scheme. We
      provide readers with estimates of alpha(MS[over -])(m(tau)(2)) and alpha(MS[over 
      ])(m(Z)(2)) in very good agreement with experimental results. Including a
      dynamical c quark makes the needed running of alpha(MS[over -]) safer.

PMID- 23004970
TI  - Key resonances in the 30P(p,gamma)31S gateway reaction for the production of
      heavy elements in ONe novae.
AB  - Material emitted as ejecta from ONe novae outbursts is observed to be rich in
      elements as heavy as Ca. The bottleneck for the synthesis of elements beyond
      sulphur is the (30)P(p,gamma)(31)S reaction. Its reaction rate is, however, not
      well determined due to uncertainties in the properties of key resonances in the
      burning regime. In the present study, gamma-ray transitions are reported for the
      first time from all key states in (31)S relevant for the (30)P(p,gamma)(31)S
      reaction. The spins and parity of these resonances have been deduced, and
      energies have been measured with the highest precision to date. The uncertainty
      in the estimated (30)P(p,gamma)(31)S reaction rate has been drastically reduced.
      The rate using this new information is typically higher than previous estimates
      based on earlier experimental data, implying a higher flux of material processed
      to high-Z elements in novae, but it is in good agreement with predictions using
      the Hauser-Feshbach approach at higher burning temperatures.

PMID- 23004966
TI  - Azimuthal collimation of long range rapidity correlations by strong color fields
      in high multiplicity hadron-hadron collisions.
AB  - The azimuthal collimation of dihadrons with large rapidity separations in high
      multiplicity p+p collisions at the LHC is described in the color glass condensate
      (CGC) effective theory [A. Dumitru, K. Dusling, F. Gelis, J. Jalilian-Marian, T.
      Lappi, and R. Venugopalan, Phys. Lett. B 697, 21 (2011).] by N(c)(2) suppressed
      multiladder QCD diagrams that are enhanced alpha(S)(-8) due to gluon saturation
      in hadron wave functions. We show that quantitative computations in the CGC
      framework are in good agreement with data from the CMS experiment on per trigger
      dihadron yields and predict further systematics of these yields with varying
      trigger p(T) and charged hadron multiplicity. Radial flow generated by
      rescattering is strongly limited by the structure of the p+p dihadron
      correlations. In contrast, radial flow explains the systematics of identical
      measurements in heavy ion collisions.

PMID- 23004971
TI  - Identification of the beta+ isovector spin monopole resonance via the 208Pb and
      90Zr(t,3He) reactions at 300 MeV/u.
AB  - The double-differential cross sections for the (208)Pb and (90)Zr(t,(3)He)
      reactions at 300 MeV/u have been measured at the RI Beam Factory at RIKEN. This
      was the first physics experiment with the SHARAQ magnetic spectrometer. The
      combined analysis of the present (t,(3)He) data and previous (n,p) data provides
      the clearest identification for the beta(+) isovector spin monopole resonance
      both in the (208)Tl and (90)Y nuclei, and puts the observations of this giant
      resonance on a firm foundation. The measured distributions of the (t,(3)He)
      monopole cross sections were well reproduced by the distorted-wave Born
      approximation calculation, where the target transition density was calculated
      with the self-consistent Hartree-Fock plus random-phase approximation using the
      T43 Skyrme interaction. A major part of the expected beta(+) isovector spin
      monopole strength was found in the measured cross section spectra.

PMID- 23004973
TI  - Structure of fermionic density matrices: complete N-representability conditions.
AB  - We present a constructive solution to the N-representability problem: a full
      characterization of the conditions for constraining the two-electron reduced
      density matrix to represent an N-electron density matrix. Previously known
      conditions, while rigorous, were incomplete. Here, we derive a hierarchy of
      constraints built upon (i) the bipolar theorem and (ii) tensor decompositions of
      model Hamiltonians. Existing conditions D, Q, G, T1, and T2, known classical
      conditions, and new conditions appear naturally. Subsets of the conditions are
      amenable to polynomial-time computations of strongly correlated systems.

PMID- 23004972
TI  - Origin of the three-body parameter universality in Efimov physics.
AB  - In recent years extensive theoretical and experimental studies of universal few
      body physics have advanced our understanding of universal Efimov physics. Whereas
      theory had been the driving force behind our understanding of Efimov physics for
      decades, recent experiments have contributed an unexpected discovery.
      Specifically, measurements have found that the so-called three-body parameter
      determining several properties of the system is universal, even though
      fundamental assumptions in the theory of the Efimov effect suggest that it should
      be a variable property that depends on the precise details of the short-range two
      and three-body interactions. The present Letter resolves this apparent
      contradiction by elucidating previously unanticipated implications of the two
      body interactions. Our study shows that the three-body parameter universality
      emerges because a universal effective barrier in the three-body potentials
      prevents the three particles from simultaneously getting close together. Our
      results also show limitations on this universality, as it is more likely to occur
      for neutral atoms but less likely to extend to light nuclei.

PMID- 23004969
TI  - Separation of pygmy dipole and M1 resonances in 90Zr by a high-resolution
      inelastic proton scattering near 0 degrees .
AB  - A high-resolution measurement of inelastic proton scattering off (90)Zr near 0
      degrees  was performed at 295 MeV with a focus on a pronounced strength
      previously reported in the low-energy tail of giant dipole resonance. A forest of
      fine structure was observed in the excitation energy region 7-12 MeV. A multipole
      decomposition analysis of the angular distribution for the forest was carried out
      using the ECIS95 distorted-wave Born approximation code with the Hartree-Fock
      plus random-phase approximation model of E1 and M1 transition densities and
      inclusion of E1 Coulomb excitation. The analysis separated pygmy dipole and M1
      resonances in the forest at E(PDR)=9.15+/-0.18 MeV with Gamma(PDR)=2.91+/-0.64
      MeV and at E(M1)=9.53+/-0.06 MeV with Gamma(M1)=2.70+/-0.17 MeV in the Lorentzian
      function, respectively. The B(E1)? value for pygmy dipole resonance over 7-11 MeV
      is 0.75+/-0.08 e(2)fm(2), which corresponds to 2.1+/-0.2% of the Thomas-Reiche
      Kuhn sum rule.

PMID- 23004974
TI  - Attosecond time-resolved imaging of molecular structure by photoelectron
      holography.
AB  - Dynamic imaging of the molecular structure of H(2)(+) is investigated by
      attosecond photoelectron holography. The interference between direct (reference)
      and backward rescattered (signal) photoelectrons in attosecond photoelectron
      holography reveals the birth time of both channels and the spatial information of
      molecular structure. This is confirmed by simulations with a semiclassical model
      and numerical solutions of the corresponding time-dependent Schrodinger equation,
      suggesting an attosecond time-resolved way of imaging molecular structure
      obtained from laser induced rescattering of ionized electrons. It is shown that
      both short and long rescattered electron trajectories can be imaged from the
      momentum distribution.

PMID- 23004975
TI  - Testing parity with atomic radiative capture of MU(-).
AB  - The next generation of "intensity frontier" facilities will bring a significant
      increase in the intensity of subrelativistic beams of MU(-). We show that the use
      of these beams in combination with thin targets of Z~30 elements opens up the
      possibility of testing parity-violating interactions of muons with nuclei via
      direct radiative capture of muons into atomic 2S orbitals. Since atomic capture
      preserves longitudinal muon polarization, the measurements of the gamma ray
      angular asymmetry in the single photon 2S(1/2)-1S(1/2) transition will offer a
      direct test of parity. We calculate the probability of atomic radiative capture
      taking into account the finite size of the nucleus to show that this process can
      dominate over the usual muonic atom cascade and that the as-yet unobserved single
      photon 2S(1/2)-1S(1/2) transition in muonic atoms can be detected in this way
      using current muon facilities.

PMID- 23004976
TI  - Generation of nonclassical microwave states using an artificial atom in 1D open
      space.
AB  - We have embedded an artificial atom, a superconducting transmon qubit, in a 1D
      open space and investigated the scattering properties of an incident microwave
      coherent state. By studying the statistics of the reflected and transmitted
      fields, we demonstrate that the scattered states can be nonclassical. In
      particular, by measuring the second-order correlation function, g((2)), we show
      photon antibunching in the reflected field and superbunching in the transmitted
      field. We also compare the elastically and inelastically scattered fields using
      both phase-sensitive and phase-insensitive measurements.

PMID- 23004977
TI  - Multipulse addressing of a Raman quantum memory: configurable beam splitting and
      efficient readout.
AB  - Quantum memories are vital to the scalability of photonic quantum information
      processing (PQIP), since the storage of photons enables repeat-until-success
      strategies. On the other hand, the key element of all PQIP architectures is the
      beam splitter, which allows us to coherently couple optical modes. Here, we show
      how to combine these crucial functionalities by addressing a Raman quantum memory
      with multiple control pulses. The result is a coherent optical storage device
      with an extremely large time bandwidth product, that functions as an array of
      dynamically configurable beam splitters, and that can be read out with
      arbitrarily high efficiency. Networks of such devices would allow fully scalable
      PQIP, with applications in quantum computation, long distance quantum
      communications and quantum metrology.

PMID- 23004978
TI  - Investigation of molecular and protein crystals by three photon polarization
      resolved microscopy.
AB  - We implement three photon fluorescence polarization resolved microscopy to
      optically investigate molecular and protein crystals. The availability of UV
      transitions using IR pulses allows analyses without fluorescence staining.
      Polarization resolved studies indicate that high-order symmetry structures can be
      revealed and that strong fluorescent energy transfer occurs between molecules. We
      show how this permits identification of a monocrystalline nature for a sample at
      the subwavelength resolution scale.

PMID- 23004979
TI  - Spectral dynamics of spatially incoherent modulation instability.
AB  - To date, all experiments in nonlinear statistical optics have relied on beams
      whose transverse spatial statistics were Gaussian. Here, we present a new
      technique to generalize these studies by using a spatial light modulator to
      create spatially incoherent beams with arbitrary spectral distributions. As a
      specific example of the new dynamics possible, we consider the spatial modulation
      instability of a partially coherent beam. We show that, for statistical beams of
      uniform intensity and equal correlation length, the underlying spectral shape
      determines the threshold and visibility of intensity modulations as well as the
      spectral profile of the growing sidebands. We demonstrate the behavior using
      statistical light, but the results will hold for any wave-kinetic system, such as
      plasma, ultracold gases, and turbulent acoustic waves.

PMID- 23004980
TI  - Vortex induced rotation dynamics of optical patterns.
AB  - We demonstrate that modulation instability leading to optical pattern formation
      can arise by using nonconventional counterpropagating beams carrying an orbital
      angular momentum (optical vortices). Such a vortex beam is injected into a
      nonlinear single feedback system. We evidence different complex patterns with
      peculiar phase singularities and rotating dynamics. We prove that the dynamics is
      induced by the vortex angular momentum and the rotation velocity depends
      nonlinearly on both the vortex topological charge and the intensity of the input
      beam.

PMID- 23004981
TI  - Intense superradiant x rays from a compact source using a nanocathode array and
      emittance exchange.
AB  - A novel method of producing intense short wavelength radiation from relativistic
      electrons is described. The electrons are periodically bunched at the wavelength
      of interest enabling in-phase superradiant emission that is far more intense than
      from unbunched electrons. The periodic bunching is achieved in steps beginning
      with an array of beamlets emitted from a nanoengineered field emission array. The
      beamlets are then manipulated and converted to a longitudinal density modulation
      via a transverse-to-longitudinal emittance exchange. Periodic bunching at short
      wavelength is shown to be possible, and the partially coherent x-ray properties
      produced by inverse Compton scattering from an intense laser are estimated. The
      proposed method increases the efficiency of x-ray production by several orders of
      magnitude, potentially enabling compact x-ray sources to produce brilliance and
      flux similar to major synchrotron facilities.

PMID- 23004982
TI  - Nonlinear plasmonic cloaks to realize giant all-optical scattering switching.
AB  - Here we extend the reach of Fano resonant coupling by combining this concept with
      cloaking and plasmonic resonances in a single nonlinear nanoparticle, in order to
      realize giant all-optical scattering nanoswitches controlled by moderate pumping
      intensities. We show that a core-shell nonlinear plasmonic particle may be
      designed to abruptly switch from being completely cloaked to being strongly
      resonant, with up to a 40 dB cross-sectional difference. Self-tunable optical
      cloaks and resonant scatterers are envisioned for use as efficient all-optical
      switches and nanomemories.

PMID- 23004983
TI  - Long-range interaction and synchronization of oscillating dissipative solitons.
AB  - We study the interaction of well-separated oscillating localized structures
      (oscillons). We show that oscillons emit weakly decaying dispersive waves, which
      lead to the formation of bound states due to harmonic synchronization. We also
      show that in optical applications the Andronov-Hopf bifurcation of stationary
      localized structures leads to a drastic increase in their interaction strength.

PMID- 23004984
TI  - Semiclassical approach to long time propagation in quantum chaos: predicting
      scars.
AB  - We present two powerful semiclassical formulas for quantum systems with
      classically chaotic dynamics, one of them being the Fourier transform of the
      other. The first formula evaluates the autocorrelation function of a state
      constructed in the neighborhood of a short periodic orbit, where the propagation
      for times greater than the Ehrenfest time is computed through the contribution of
      homoclinic orbits. The second formula evaluates the square of the overlap of the
      proposed state with the eigenstates of the system, providing valuable information
      about the scarring phenomenon. Both expressions are successfully verified in the
      Bunimovich stadium billiard.

PMID- 23004985
TI  - Passive phase noise cancellation scheme.
AB  - We introduce a new method for reducing phase noise in oscillators, thereby
      improving their frequency precision. The noise reduction is realized by a passive
      device consisting of a pair of coupled nonlinear resonating elements that are
      driven parametrically by the output of a conventional oscillator at a frequency
      close to the sum of the linear mode frequencies. Above the threshold for
      parametric instability, the coupled resonators exhibit self-oscillations which
      arise as a response to the parametric driving, rather than by application of
      active feedback. We find operating points of the device for which this periodic
      signal is immune to frequency noise in the driving oscillator, providing a way to
      clean its phase noise. We present results for the effect of thermal noise to
      advance a broader understanding of the overall noise sensitivity and the
      fundamental operating limits.

PMID- 23004986
TI  - Hydrodynamic interaction between a spherical particle and an elastic surface: a
      gentle probe for soft thin Films.
AB  - We study the hydrodynamic interaction between a sphere and an elastic surface at
      a nanoscale with a dynamic surface force apparatus. We show that the interplay
      between viscous forces and elastic deformations leads to very rich scaling
      properties of the force response, providing a unique signature of the surface
      elastic behavior. These properties are illustrated on three different examples: a
      thick elastomer, a thin elastomer film, and a layer of micrometric bubbles. We
      show that this fluid probing allows one to measure the Young's modulus of
      surfaces and soft thin layers at distance, without any direct solid-solid
      contact.

PMID- 23004987
TI  - Obstructed breakup of slender drops in a microfluidic T junction.
AB  - In this Letter we present a theoretical analysis of the droplet breakup with
      "permanent obstruction" in a microfluidic T junction [M.-C. Jullien et al., Phys.
      Fluids 21, 072001 (2009)]. The proposed theory is based on a simple geometric
      construction for the interface shape combined with Tanner's law for the local
      contact angle. The resulting scaling of the droplet deformation with time and
      capillary number is in excellent agreement with the results of direct numerical
      simulations and prior experiments. More rigorous analysis based on the
      lubrication approximation reveals a self-similar behavior analogous to the
      classical problem of a droplet spreading over a preexisting liquid film.

PMID- 23004988
TI  - Level splitting at macroscopic scale.
AB  - A walker is a classical self-propelled wave particle association moving on a
      fluid interface. Two walkers can interact via their waves and form orbiting bound
      states with quantized diameters. Here we probe the behavior of these bound states
      when setting the underlying bath in rotation. We show that the bound states are
      driven by the wave interaction between the walkers and we observe a level
      splitting at macroscopic scale induced by the rotation. Using the analogy between
      Coriolis and Lorentz forces, we show that this effect is the classical equivalent
      to Zeeman splitting of atomic energy levels.

PMID- 23004989
TI  - Capillary fracturing in granular media.
AB  - We study the displacement of immiscible fluids in deformable, noncohesive
      granular media. Experimentally, we inject air into a thin bed of water-saturated
      glass beads and observe the invasion morphology. The control parameters are the
      injection rate, the bead size, and the confining stress. We identify three
      invasion regimes: capillary fingering, viscous fingering, and "capillary
      fracturing," where capillary forces overcome frictional resistance and induce the
      opening of conduits. We derive two dimensionless numbers that govern the
      transition among the different regimes: a modified capillary number and a
      fracturing number. The experiments and analysis predict the emergence of
      fracturing in fine-grained media under low confining stress, a phenomenon that
      likely plays a fundamental role in many natural processes such as primary oil
      migration, methane venting from lake sediments, and the formation of desiccation
      cracks.

PMID- 23004990
TI  - Exploring the origins of turbulence in multiphase flow using compressed sensing
      MRI.
AB  - Ultrafast magnetic resonance imaging, employing spiral reciprocal space sampling
      and compressed sensing image reconstruction, is used to acquire velocity maps of
      the liquid phase in gas-liquid multiphase flows. Velocity maps were acquired at a
      rate of 188 frames per second. The method enables quantitative characterization
      of the wake dynamics of single bubbles and bubble swarms. To illustrate this, we
      use the new technique to demonstrate the role of bubble wake vorticity in driving
      bubble secondary motions, and in governing the structure of turbulence in
      multiphase flows.

PMID- 23004991
TI  - von Karman vortex street within an impacting drop.
AB  - The splashing of a drop impacting onto a liquid pool produces a range of
      different sized microdroplets. At high impact velocities, the most significant
      source of these droplets is a thin liquid jet emerging at the start of the impact
      from the neck that connects the drop to the pool. We use ultrahigh-speed video
      imaging in combination with high-resolution numerical simulations to show how
      this ejecta gives way to irregular splashing. At higher Reynolds numbers, its
      base becomes unstable, shedding vortex rings into the liquid from the free
      surface in an axisymmetric von Karman vortex street, thus breaking the ejecta
      sheet as it forms.

PMID- 23004992
TI  - Polarization transfer of bremsstrahlung arising from spin-polarized electrons.
AB  - We report on a study of the polarization transfer between transversely polarized
      incident electrons and the emitted x rays for electron-atom bremsstrahlung. By
      means of Compton polarimetry we performed for the first time an energy
      differential measurement of the complete properties of bremsstrahlung emission
      related to linear polarization, i.e., the degree of linear polarization as well
      as the orientation of the polarization axis. For the high-energy end of the
      bremsstrahlung continuum the experimental results for both observables show a
      high sensitivity on the initial electron spin polarization and prove that the
      polarization orientation is virtually independent of the photon energy.

PMID- 23004993
TI  - Stochastic modeling of intermittent scrape-off layer plasma fluctuations.
AB  - Single-point measurements of fluctuations in the scrape-off layer of magnetized
      plasmas are generally found to be dominated by large-amplitude bursts which are
      associated with radial motion of bloblike structures. A stochastic model for
      these fluctuations is presented, with the plasma density given by a random
      sequence of bursts with a fixed wave form. When the burst events occur in
      accordance to a Poisson process, this model predicts a parabolic relation between
      the skewness and kurtosis moments of the plasma fluctuations. In the case of an
      exponential wave form and exponentially distributed burst amplitudes, the
      probability density function for the fluctuation amplitudes is shown to be a
      Gamma distribution with the scale parameter given by the average burst amplitude,
      and the shape parameter given by the ratio of the burst duration and waiting
      times.

PMID- 23004994
TI  - Supersolid vortex crystals in Rydberg-dressed Bose-Einstein condensates.
AB  - We study rotating quasi-two-dimensional Bose-Einstein condensates, in which atoms
      are dressed to a highly excited Rydberg state. This leads to weak effective
      interactions that induce a transition to a mesoscopic supersolid state.
      Considering slow rotation, we determine its superfluidity using quantum Monte
      Carlo simulations as well as mean field calculations. For rapid rotation, the
      latter reveal an interesting competition between the supersolid crystal structure
      and the rotation-induced vortex lattice that gives rise to new phases, including
      arrays of mesoscopic vortex crystals.

PMID- 23004995
TI  - Surface modes of coherent spinodal decomposition.
AB  - We use linear stability theory and numerical simulations to show that spontaneous
      phase separation in elastically coherent solids is fundamentally altered by the
      presence of free surfaces. Because of misfit stress relaxation near surfaces,
      phase separation is mediated by unique surface modes of spinodal decomposition
      that have faster kinetics than bulk modes and are unstable even when spinodal
      decomposition is suppressed in the bulk. Consequently, in the presence of free
      surfaces, the limit of metastability of supersaturated solid solutions of
      crystalline materials is shifted from the coherent to chemical spinodal.

PMID- 23004996
TI  - Experimental observations of dynamic critical phenomena in a lipid membrane.
AB  - Near a critical point, the time scale of thermally induced fluctuations diverges
      in a manner determined by the dynamic universality class. Experiments have
      verified predicted three-dimensional dynamic critical exponents in many systems,
      but similar experiments in two dimensions have been lacking for the case of
      conserved order parameter. Here we analyze the time-dependent correlation
      functions of a quasi-two-dimensional lipid bilayer in water to show that its
      critical dynamics agree with a recently predicted universality class. In
      particular, the effective dynamic exponent z(eff) crosses over from ~2 to ~3 as
      the correlation length of fluctuations exceeds a hydrodynamic length set by the
      membrane and bulk viscosities.

PMID- 23004997
TI  - Full counting statistics for orbital-degenerate impurity Anderson model with
      Hund's rule exchange coupling.
AB  - We study nonequilibrium current fluctuations through a quantum dot, which
      includes a ferromagnetic Hund's rule coupling J, in the low-energy Fermi liquid
      regime using the renormalized perturbation theory. The resulting cumulant for the
      current distribution in the particle-hole symmetric case shows that spin-triplet
      and spin-singlet pairs of quasiparticles are formed in the current due to the
      Hund's rule coupling, and these pairs enhance the current fluctuations. In the
      fully screened higher-spin Kondo limit, the Fano factor takes a value
      F(b)=(9M+6)/(5M+4) determined by the orbital degeneracy M. We also investigate
      the crossover between the small and large J limits in the two-orbital case M=2,
      using the numerical renormalization group approach.

PMID- 23004998
TI  - Zero modes and charged Skyrmions in graphene bilayer.
AB  - We show that the electric charge of the Skyrmion in the vector order parameters
      that characterize the quantum anomalous spin Hall state and the layer
      antiferromagnet in a graphene bilayer is four and zero, respectively. The result
      is based on the demonstration that a vortex configuration in two broken symmetry
      states in bilayer graphene with the quadratic band crossing has the number of
      zero modes doubled relative to the single layer. The doubling can be understood
      as a result of Kramers's theorem implied by the "pseudo time reversal" symmetry
      of the vortex Hamiltonian. Disordering the quantum anomalous spin Hall state by
      Skyrmion condensation should produce a superconductor of an elementary charge 4e.

PMID- 23004999
TI  - Crossover from Coulomb blockade to quantum Hall effect in suspended graphene
      nanoribbons.
AB  - Suspended graphene nanoribbons formed during current annealing of suspended
      graphene flakes have been investigated experimentally. Transport measurements
      show the opening of a transport gap around charge neutrality due to the formation
      of "Coulomb islands", coexisting with quantum Hall conductance plateaus appearing
      at moderate values of the magnetic field B. Upon increasing B, the transport gap
      is rapidly suppressed, and is taken over by a much larger energy gap due to
      electronic correlations. Our observations show that suspended nanoribbons allow
      the investigation of phenomena that could not so far be accessed in ribbons on
      SiO(2) substrates.

PMID- 23005000
TI  - Theory of space charge limited currents.
AB  - Space-charge-limited currents are important in energy devices such as solar cells
      and light-emitting diodes, but the available theory from the 1950s finds it
      necessary to postulate defect states that are distributed in energy in order to
      match data. Here, we show that this postulate is not warranted. Instead, we
      demonstrate that dopants and the concomitant Frenkel effect, which have been
      neglected, control the shape of measured current-voltage characteristics. We also
      account for the observed peak in the noise power. The new theory can anchor
      efforts to develop experimental techniques to measure deep-trap levels.

PMID- 23005001
TI  - Fractional topological phases and broken time-reversal symmetry in strained
      graphene.
AB  - We show that strained or deformed honeycomb lattices are promising platforms to
      realize fractional topological quantum states in the absence of any magnetic
      field. The strain-induced pseudomagnetic fields are oppositely oriented in the
      two valleys and can be as large as 60-300 T as reported in recent experiments.
      For strained graphene at neutrality, a spin- or a valley-polarized state is
      predicted depending on the value of the on-site Coulomb interaction. At
      fractional filling, the unscreened Coulomb interaction leads to a valley
      polarized fractional quantum Hall liquid which spontaneously breaks time-reversal
      symmetry. Motivated by artificial graphene systems, we consider tuning the short
      range part of interactions and demonstrate that exotic valley symmetric states,
      including a valley fractional topological insulator and a spin triplet
      superconductor, can be stabilized by such interaction engineering.

PMID- 23005002
TI  - Multi-Weyl topological semimetals stabilized by point group symmetry.
AB  - We perform a complete classification of two-band k.p theories at band crossing
      points in 3D semimetals with n-fold rotation symmetry and broken time-reversal
      symmetry. Using this classification, we show the existence of new 3D topological
      semimetals characterized by C(4,6)-protected double-Weyl nodes with quadratic in
      plane (along k(x,y)) dispersion or C(6)-protected triple-Weyl nodes with cubic in
      plane dispersion. We apply this theory to the 3D ferromagnet HgCr(2)Se(4) and
      confirm it is a double-Weyl metal protected by C(4) symmetry. Furthermore, if the
      direction of the ferromagnetism is shifted away from the [001] axis to the [111]
      axis, the double-Weyl node splits into four single Weyl nodes, as dictated by the
      point group S(6) of that phase. Finally, we discuss experimentally relevant
      effects including the splitting of multi-Weyl nodes by applying a C(n) breaking
      strain and the surface Fermi arcs in these new semimetals.

PMID- 23005003
TI  - Conductance-driven change of the Kondo effect in a single cobalt atom.
AB  - A low-temperature scanning tunneling microscope is employed to build a junction
      comprising a Co atom bridging a copper-coated tip and a Cu(100) surface. An
      Abrikosov-Suhl-Kondo resonance is evidenced in the differential conductance and
      its width is shown to vary exponentially with the ballistic conductance for all
      tips employed. Using a theoretical description based on the Anderson model, we
      show that the Kondo effect and the total conductance are related through the
      atomic relaxations affecting the environment of the Co atom.

PMID- 23005004
TI  - Manipulation of electronic transport in the Bi(111) surface state.
AB  - We demonstrate the controlled manipulation of the 2D-electronic transport in the
      surface state of Bi(111) through the deposition of small amounts of Bi to
      generate adatoms and 2D islands as additional scatterers. The corresponding
      increase in resistance is recorded in situ and in real time. Model calculations
      based on mean-field nucleation theory reveal a constant scattering efficiency of
      adatoms and of small 2D Bi islands, independent of their size. This finding is
      supported by a detailed scanning tunneling microscopy and spectroscopy study at 5
      K which shows a highly anisotropic scattering pattern surrounding each surface
      protrusion.

PMID- 23005005
TI  - Topological phase transition in layered GaS and GaSe.
AB  - By fully relativistic first principles calculations, we predict that appropriate
      strain engineering of layered GaX (X=S, Se) leads to a new class of three
      dimensional topological insulators with an excitation gap of up to 135 meV. Our
      results provide a new perspective on the formation of three-dimensional
      topological insulators. Band inversion can be induced by strain only, without
      considering any spin-orbit coupling. The latter, however, is indispensable for
      the formation of local band gaps at the crossing points of the inverted bands.
      Our study indicates that three-dimensional topological insulators can also be
      realized in materials which comprise light elements only.

PMID- 23005006
TI  - Room temperature giant and linear magnetoresistance in topological insulator
      Bi2Te3 nanosheets.
AB  - Topological insulators, a new class of condensed matter having bulk insulating
      states and gapless metallic surface states, have demonstrated fascinating quantum
      effects. However, the potential practical applications of the topological
      insulators are still under exploration worldwide. We demonstrate that nanosheets
      of a Bi(2)Te(3) topological insulator several quintuple layers thick display
      giant and linear magnetoresistance. The giant and linear magnetoresistance
      achieved is as high as over 600% at room temperature, with a trend towards
      further increase at higher temperatures, as well as being weakly temperature
      dependent and linear with the field, without any sign of saturation at measured
      fields up to 13 T. Furthermore, we observed a magnetic field induced gap below 10
      K. The observation of giant and linear magnetoresistance paves the way for 3D
      topological insulators to be useful for practical applications in
      magnetoelectronic sensors such as disk reading heads, mechatronics, and other
      multifunctional electromagnetic applications.

PMID- 23005007
TI  - Theory of a continuous stripe melting transition in a two-dimensional metal: a
      possible application to cuprate superconductors.
AB  - We construct a theory of continuous stripe melting quantum phase transitions in
      two-dimensional metals and the associated Fermi surface reconstruction. Such
      phase transitions are strongly coupled but yet theoretically tractable in
      situations where the stripe ordering is destroyed by proliferating doubled
      dislocations of the charge stripe order. The resulting non-Landau quantum
      critical point has strong stripe fluctuations which we show decouple dynamically
      from the Fermi surface even though static stripe ordering reconstructs the Fermi
      surface. We discuss connections to various stripe phenomena in the cuprates. We
      point out several puzzling aspects of old experimental results [G. Aeppli et al.,
      Science 278, 1432 (1997)] on singular stripe fluctuations in the cuprates, and
      provide a possible explanation within our theory. These results may thus have
      been the first observation of non-Landau quantum criticality in an experiment.

PMID- 23005008
TI  - Gap opening and orbital modification of superconducting FeSe above the structural
      distortion.
AB  - We utilize steady-state and transient optical spectroscopies to examine the
      responses of nonthermal quasiparticles with respect to orbital modifications in
      normal-state iron-chalcogenide superconductors. The dynamics shows the emergence
      of gaplike quasiparticles (associated with a ~36 meV energy gap) with a
      coincident transfer of the optical spectral weight in the visible range, at
      temperatures above the structural distortion. Our observations suggest that
      opening of the high-temperature gap and the lattice symmetry breaking are
      possibly driven by short-range orbital and/or charge orders, implicating a close
      correlation between electronic nematicity and precursor order in iron-based
      superconductors.

PMID- 23005009
TI  - Temperature dependence of the electronic structure and Fermi-surface
      reconstruction of Eu(1-x)Gd(x)O through the ferromagnetic metal-insulator
      transition.
AB  - We present angle-resolved photoemission spectroscopy of Eu(1-x)Gd(x)O through the
      ferromagnetic metal-insulator transition. In the ferromagnetic phase, we observe
      Fermi surface pockets at the Brillouin zone boundary, consistent with density
      functional theory, which predicts a half-metal. Upon warming into the
      paramagnetic state, our results reveal a strong momentum-dependent evolution of
      the electronic structure, where the metallic states at the zone boundary are
      replaced by pseudogapped states at the Brillouin zone center due to the absence
      of magnetic long-range order of the Eu 4f moments.

PMID- 23005010
TI  - Extended Skyrmion phase in epitaxial FeGe(111) thin films.
AB  - The Skyrmion state in epitaxial B20 FeGe(111) thin films, determined by the
      topological Hall effect, is greatly extended in the phase diagram to cover all
      temperatures up to the Curie temperature T(C)~271 K and over a wide magnetic
      field range that includes a zero magnetic field. The properties of the Skyrmion
      phase can be controlled and manipulated by the film thickness, which has a strong
      effect on the stabilization of Skyrmions.

PMID- 23005011
TI  - Tuning the optical gap of nanometer-size diamond cages by sulfurization: a time
      dependent density functional study.
AB  - The optical gap of nanometer sized diamond cages, i.e., diamondoids, lies in the
      ultraviolet spectral region. Here we show by hybrid functional based time
      dependent density-functional calculations that, by varying the number of C=S
      double bonds at the surface of diamondoids, the absorption onset can be tuned
      toward the infrared spectral region. Our finding has an important implication for
      in vivo biological applications where toxic and unstable dye molecules may be
      substituted by the luminescent sulfurized diamondoids.

PMID- 23005012
TI  - Terahertz excitation of a coherent lambda-type three-level system of exciton
      polariton modes in a quantum-well microcavity.
AB  - Interactions of few-cycle terahertz pulses with the induced optical polarization
      in a quantum-well microcavity reveal that the lower and higher exciton-polariton
      modes together with the optically forbidden 2p-exciton state form a unique Lambda
      type three-level system. Pronounced nonlinearities are observed via time-resolved
      strong-terahertz and weak-optical excitation spectroscopy and explained with a
      fully microscopic theory. The results show that the terahertz pulses strongly
      couple the exciton-polariton states to the 2p-exciton state while no resonant
      transition between the two polariton levels is observed.

PMID- 23005013
TI  - Femtosecond single-shot imaging of nanoscale ferromagnetic order in Co/Pd
      multilayers using resonant x-ray holography.
AB  - We present the first single-shot images of ferromagnetic, nanoscale spin order
      taken with femtosecond x-ray pulses. X-ray-induced electron and spin dynamics can
      be outrun with pulses shorter than 80 fs in the investigated fluence regime, and
      no permanent aftereffects in the samples are observed below a fluence of 25
      mJ/cm(2). Employing resonant spatially muliplexed x-ray holography results in a
      low imaging threshold of 5 mJ/cm(2). Our results open new ways to combine
      ultrafast laser spectroscopy with sequential snapshot imaging on a single sample,
      generating a movie of excited state dynamics.

PMID- 23005014
TI  - Triplets contribute to both an increase and loss in fluorescent yield in organic
      light emitting diodes.
AB  - Nonradiative triplets in fluorescent organic light emitting diodes (OLEDs) can
      lead to increased efficiency through triplet-triplet annihilation, or to
      decreased efficiency due to singlet-triplet annihilation. We study the tradeoff
      between the two processes from the electroluminescence transients of an OLED
      comprising a tetraphenyldibenzoperiflanthene (DBP) doped rubrene emissive layer,
      whose emission spectrum peaks at a wavelength of 610 nm. The electroluminescent
      transients in the current density range, 4 mA/cm(2)<J<57 A/cm(2), are modeled
      based on singlet and triplet density dynamics. Our analysis shows that triplets
      positively contribute to the OLED efficiency at J<2.2 A/cm(2), while decreasing
      the efficiency at higher J. The high OLED peak external quantum efficiency of
      6.7% and rapid efficiency roll-off with J are quantitatively explained by the
      tradeoff between triplet-triplet and singlet-triplet annihilation. The model
      suggests optimal materials properties needed for achieving high efficiency at
      high brightness in fluorescent OLEDs.

PMID- 23005015
TI  - Slow hopping and spin dephasing of Coulombically bound polaron pairs in an
      organic semiconductor at room temperature.
AB  - Polaron pairs are intermediate electronic states that are integral to the
      optoelectronic conversion process in organic semiconductors. Here, we report on
      electrically detected spin echoes arising from direct quantum control of polaron
      pair spins in an organic light-emitting diode at room temperature. This approach
      reveals phase coherence on a microsecond time scale, and offers a direct way to
      probe charge recombination and dissociation processes in organic devices,
      revealing temperature-independent intermolecular carrier hopping on slow time
      scales. In addition, the long spin phase coherence time at room temperature is of
      potential interest for developing quantum-enhanced sensors and information
      processing systems which operate at room temperature.

PMID- 23005016
TI  - Size-topology relations in packings of grains, emulsions, foams, and biological
      cells.
AB  - Particulate packings in 3D are used to study the effects of compression and
      polydispersity on the geometry of the tiling in these systems. We find that the
      dependence of the neighbor number on cell size is quasilinear in the monodisperse
      case and becomes nonlinear above a threshold polydispersity, independent of the
      method of creation of the tiling. These size-topology relations can be described
      by a simple analytical theory, which quantifies the effects of positional
      disorder in the monodisperse case and those of size disorder in the polydisperse
      case and is applicable in two and three dimensions. The theory thus gives a
      unifying framework for a wide range of amorphous systems, ranging from biological
      tissues, foams, and bidisperse disks to compressed emulsions and granular matter.

PMID- 23005017
TI  - Inferring where and when replication initiates from genome-wide replication
      timing data.
AB  - Based on an analogy between DNA replication and one dimensional nucleation-and
      growth processes, various attempts to infer the local initiation rate I(x,t) of
      DNA replication origins from replication timing data have been developed in the
      framework of phase transition kinetics theories. These works have all used curve
      fit strategies to estimate I(x,t) from genome-wide replication timing data. Here,
      we show how to invert analytically the Kolmogorov-Johnson-Mehl-Avrami model and
      extract I(x,t) directly. Tests on both simulated and experimental budding-yeast
      data confirm the location and firing-time distribution of replication origins.

PMID- 23005018
TI  - Quantitative prediction of the phase diagram of DNA-functionalized nanosized
      colloids.
AB  - We present a coarse-grained model of DNA-functionalized colloids that is
      computationally tractable. Importantly, the model parameters are solely based on
      experimental data. Using this highly simplified model, we can predict the phase
      behavior of DNA-functionalized nanocolloids without assuming pairwise additivity
      of the intercolloidal interactions. Our simulations show that, for nanocolloids,
      the assumption of pairwise additivity leads to substantial errors in the estimate
      of the free energy of the crystal phase. We compare our results with available
      experimental data and find that the simulations predict the correct structure of
      the solid phase and yield a very good estimate of the melting temperature.
      Current experimental estimates for the contour length and persistence length of
      single-stranded (ss) DNA sequences are subject to relatively large uncertainties.
      Using the best available estimates, we obtain predictions for the crystal lattice
      constants that are off by a few percent: this indicates that more accurate
      experimental data on ssDNA are needed to exploit the full power of our coarse
      grained approach.

PMID- 23005019
TI  - Precise orientation of a single C60 molecule on the tip of a scanning probe
      microscope.
AB  - We show that the precise orientation of a C(60) molecule which terminates the tip
      of a scanning probe microscope can be determined with atomic precision from
      submolecular contrast images of the fullerene cage. A comparison of experimental
      scanning tunneling microscopy data with images simulated using computationally
      inexpensive Huckel theory provides a robust method of identifying molecular
      rotation and tilt at the end of the probe microscope tip. Noncontact atomic force
      microscopy resolves the atoms of the C(60) cage closest to the surface for a
      range of molecular orientations at tip-sample separations where the molecule
      substrate interaction potential is weakly attractive. Measurements of the C(60)
      C(60) pair potential acquired using a fullerene-terminated tip are in excellent
      agreement with theoretical predictions based on a pairwise summation of the van
      der Waals interactions between C atoms in each cage, i.e., the Girifalco
      potential [L. Girifalco, J. Phys. Chem. 95, 5370 (1991)].

PMID- 23005020
TI  - Dynamic clustering in active colloidal suspensions with chemical signaling.
AB  - In this Letter, we explore experimentally the phase behavior of a dense active
      suspension of self-propelled colloids. In addition to a solidlike and gaslike
      phase observed for high and low densities, a novel cluster phase is reported at
      intermediate densities. This takes the form of a stationary assembly of dense
      aggregates-resulting from a permanent dynamical merging and separation of active
      colloids-whose average size grows with activity as a linear function of the self
      propelling velocity. While different possible scenarios can be considered to
      account for these observations-such as a generic velocity weakening instability
      recently put forward-we show that the experimental results are reproduced
      mathematically by a chemotactic aggregation mechanism, originally introduced to
      account for bacterial aggregation and accounting here for diffusiophoretic
      chemical interaction between colloidal swimmers.

PMID- 23005021
TI  - Structural relaxations of thin polymer films.
AB  - Time-dependent changes of thermodynamic properties due to structural relaxations
      and physical aging occur in all glasses. We show that the physical aging of thin
      supported films of star-shaped macromolecules, with f arms of length N(arm),
      exhibits average aging dynamics that are sensitive to f and N(arm). Regions of
      the films in proximity to interfaces age at substantially different rates than
      the interior of the film; this is also true of linear chain systems. This
      behavior may be reconciled in terms of a universal picture that accounts only for
      changes in the local T(g) of the films.

PMID- 23005022
TI  - Spontaneous helicity of a polymer with side loops confined to a cylinder.
AB  - Inspired by recent experiments on the spatial organization of bacterial
      chromosomes, we consider a type of "bottle-brush" polymer consisting of a
      flexible backbone chain, to which flexible side loops are connected. We show that
      such a model with an open linear backbone spontaneously adopts a helical
      structure with a well-defined pitch when confined to small cylindrical volume.
      This helicity persists over a range of sizes and aspect ratios of the cylinder,
      provided the packing fraction of the chain is suitably large. We analyze these
      results in terms of the interplay between the effective stiffness and actual
      intrachain packing effects caused by the side loops in response to the
      confinement.

PMID- 23005023
TI  - Size limit for particle-stabilized emulsion droplets under gravity.
AB  - We demonstrate that emulsion droplets stabilized by interfacial particles become
      unstable beyond a size threshold set by gravity. This holds not only for colloids
      but also for supracolloidal glass beads, using which we directly observe the
      ejection of particles near the droplet base. The number of particles acting
      together in these ejection events decreases with time until a stable acornlike
      configuration is reached. Stability occurs when the weight of all remaining
      particles is less than the interfacial binding force of one particle. We also
      show the importance of the curvature of the droplet surface in promoting particle
      ejection.

PMID- 23005024
TI  - How to capture active particles.
AB  - In many applications, it is important to catch collections of autonomously
      navigating microbes and man-made microswimmers in a controlled way. Using
      computer simulation of a two-dimensional system of self-propelled rods we show
      that a static chevron-shaped wall represents an excellent trapping device for
      self-motile particles. Its catching efficiency can be controlled by varying the
      apex angle of the trap which defines the sharpness of the cusp. Upon decreasing
      the angle we find a sequence of three emergent states: no trapping at wide angles
      followed by a sharp transition towards complete trapping at medium angles and a
      crossover to partial trapping at small cusp angles. A generic trapping "phase
      diagram" maps out the conditions at which the capture of active particles at a
      given density is rendered optimal.

PMID- 23005025
TI  - Comment on "Low-power laser deformation of an air-liquid interface".

PMID- 23005027
TI  - Comment on "Dislocations jam at any density".

PMID- 23005029
TI  - The application of graphene oxide in drug delivery.
AB  - INTRODUCTION: As a shining star in material science, graphene oxide (GO) and its
      derivatives possess potential applications in a variety of areas. Among them, the
      application of GO to drug delivery has attracted ever-increasing interest in the
      past few years. AREAS COVERED: In this article, the authors summarize the latest
      progress of utilizing GO in the field of drug delivery. In particular, the
      functionalization of GO, cytotoxicity of GO and its derivatives, in vitro and in
      vivo drug delivery and the comparison with carbon nanotube-based delivery systems
      are discussed. Future perspectives and possible challenges in this emerging field
      are briefly described. EXPERT OPINION: GO and its derivatives are highly
      attractive for the application to drug delivery due to their exceptional
      physiochemical properties and unique planar structure in spite of some existing
      challenges, such as the reproducibly smart functionalization of GO and the
      investigation of its long-term toxicology.

PMID- 23005030
TI  - Bayesian inference for the causal effect of mediation.
AB  - We propose a nonparametric Bayesian approach to estimate the natural direct and
      indirect effects through a mediator in the setting of a continuous mediator and a
      binary response. Several conditional independence assumptions are introduced
      (with corresponding sensitivity parameters) to make these effects identifiable
      from the observed data. We suggest strategies for eliciting sensitivity
      parameters and conduct simulations to assess violations to the assumptions. This
      approach is used to assess mediation in a recent weight management clinical
      trial.

PMID- 23005031
TI  - Unfolding of cytochrome C upon interaction with azobenzene-modified copolymers.
AB  - Hydrophilic or amphiphilic macromolecules are common organic matrices used to
      encapsulate and protect fragile drugs such as proteins. Polymer cargoes are in
      addition designed for remote control of protein delivery, upon imparting the
      macromolecules with stimuli-responsive properties, such as light-triggered
      polarity switches. The effect of interaction between polymers and proteins on the
      stability of the proteins is, however, rarely investigated. Here we studied the
      unfolding/folding equilibrium of cytochrome c (cyt c) under its oxidized or
      reduced forms, in the presence of various amphiphilic copolymers (by circular
      dichroism and intrinsic fluorescence measurements). As models of stimuli
      responsive amphiphilic chains, we considered poly(acrylic acid) derivatives,
      modified to contain hydrophobic, light-responsive azobenzene moieties. These
      copolymers are, thus, capable to develop both ionic (under their sodium forms at
      pH > 8) and hydrophobic associations with the basic protein cyt c (isoelectric
      point of 10.0). In aqueous buffer upon increasing urea concentrations, cyt c
      underwent unfolding, at [urea] of 9-10 M, which was analyzed under the framework
      of the equilibrium between two states (native-unfolded). In the presence of
      polymers, the native folding of cyt c was preserved at low concentrations of urea
      (typically <4M). However, the presence of polymers facilitated unfolding, which
      occurred at urea concentrations lowered by 2-4 M as compared to unfolding in the
      absence of polymers (polymer/cyt c ratio of 1:1 g/g). The predominant
      contribution of coulombic interactions was shown by both the lack of significant
      impact of the amount of (neutral) azobenzene moieties in the copolymers and the
      disappearance of destabilization at ionic strength higher than 150 mM. In
      addition, stability was similar to that of an isolated cyt c, in the presence of
      a neutral chain bearing acryloyl(oligoethyleneoxide) units instead of the ionized
      sodium acrylate moieties. DSC measurements showed that in the presence of
      polymers, cyt c is thermally unfolded in aqueous buffer at temperatures lowered
      by >20  degrees C as compared to thermal unfolding in the absence of polymers.
      Upon exposure to UV light, properties of the polymers chains were perturbed in
      situ, upon cis/trans isomerization of the azobenzene groups. In polymers
      displaying a photoresponsive polarity and hydrophobicity switch (conventional
      azobenzene), the stability of cyt c was not affected by the exposure to light. In
      contrast, when photoionization occurred (using an hydroxyl-azobenzene whose pK(a)
      can be photoshifted), unfolding was initiated upon exposure to light. Altogether,
      these results show that coulombic binding is a predominant driving force that
      facilitates unfolding in water/urea solutions. In regard to the design of light
      responsive systems for protein handling and control of folding, we conclude that
      remote control of the coulombic interaction upon photoionization of chromophores
      can be more efficient than the more conventional photomodulation of polarity.

PMID- 23005032
TI  - Coexistence of plant and algal energy dissipation mechanisms in the moss
      Physcomitrella patens.
AB  - Although light is the source of energy for photosynthetic organisms, it causes
      oxidative stress when in excess. Plants and algae prevent reactive oxygen species
      (ROS) formation by activation of nonphotochemical quenching (NPQ), which
      dissipates excess excitation energy as heat. Although NPQ is found in both algae
      and plants, these organisms rely on two different proteins for its activation,
      Light harvesting complex stress-related (LHCSR) and Photosystem II subunit S
      (PSBS). In the moss Physcomitrella patens, both proteins are present and active.
      Several P. patens lines depleted in or over-expressing PSBS and/or LHCSR at
      various levels were generated by exploiting the ability of Physcomitrella to
      undergo homologous recombination. The analysis of the transgenic lines showed
      that either protein is sufficient, alone, for NPQ activation independently of the
      other, supporting the idea that they rely on different activation mechanisms.
      Modulation of PSBS and/or LHCSR contents was found to be correlated with NPQ
      amplitude, indicating that plants and algae can directly modulate their ability
      to dissipate energy simply by altering the accumulation level of one or both of
      these proteins. The availability of a large range of P. patens genotypes
      differing in PSBS and LHCSR content allowed comparison of their activation
      mechanisms and discussion of implications for the evolution of photoprotection
      during land colonization.

PMID- 23005033
TI  - Facilitating energy savings with programmable thermostats: evaluation and
      guidelines for the thermostat user interface.
AB  - Thermostats control heating and cooling in homes - representing a major part of
      domestic energy use - yet, poor ergonomics of these devices has thwarted efforts
      to reduce energy consumption. Theoretically, programmable thermostats can reduce
      energy by 5-15%, but in practice little to no savings compared to manual
      thermostats are found. Several studies have found that programmable thermostats
      are not installed properly, are generally misunderstood and have poor usability.
      After conducting a usability study of programmable thermostats, we reviewed
      several guidelines from ergonomics, general device usability, computer-human
      interfaces and building control sources. We analysed the characteristics of
      thermostats that enabled or hindered successfully completing tasks and in a
      timely manner. Subjects had higher success rates with thermostat displays with
      positive examples of guidelines, such as visibility of possible actions,
      consistency and standards, and feedback. We suggested other guidelines that
      seemed missing, such as navigation cues, clear hierarchy and simple decision
      paths. PRACTITIONER SUMMARY: Our evaluation of a usability test of five
      residential programmable thermostats led to the development of a comprehensive
      set of specific guidelines for thermostat design including visibility of possible
      actions, consistency, standards, simple decision paths and clear hierarchy.
      Improving the usability of thermostats may facilitate energy savings.

PMID- 23005034
TI  - A convergent, unified approach to functionalized fluoro- and trifluoromethyl
      alkenes.
AB  - A modular, convergent, and operationally simple route to trifluoromethyl alkenes
      and vinyl fluorides involving a unique carbon-oxygen bond homolysis is reported.
      Highly functionalized trifluoromethyl alkenes and vinyl fluorides were obtained
      in good yields and good selectivity.

PMID- 23005035
TI  - Stereoselective synthesis of conjugated fluoro enynes.
AB  - Metalation-electrophilic fluorination of TMS- and TIPS-protected 1,3-benzothiazol
      2-yl (BT) propargyl sulfones gave corresponding BT fluoropropargyl sulfones,
      Julia-Kocienski reagents for the synthesis of fluoro enynes. Both reagents
      reacted with aldehydes under mild DBU- or LHMDS-mediated conditions, giving high
      yields of conjugated fluoro enynes with E-stereoselectivity. In comparison to DBU
      mediated reactions, stereoselectivity was higher in low-temperature LHMDS
      mediated reactions. Two ketones were shown to react as well, using LHMDS as base.
      In situ removal of the TMS group gave terminal conjugated 2-fluoro 1,3-enynes.
      Synthetic utility of the fluoro enynes was demonstrated by conversion to internal
      alkynes and to stereoisomeric fluoro dienes via Sonogashira and Heck couplings.

PMID- 23005036
TI  - Aluminum oxide nanoparticles as carriers and adjuvants for eliciting antibodies
      from non-immunogenic haptens.
AB  - Functionalized nanomaterials have applications yet to be discovered, especially
      in the biological field and, in particular, the in vivo production of antibodies.
      In this paper, we show that aluminum oxide nanoparticles that are covalently
      coupled to haptens (small molecular mass compounds) activate the immune system,
      eliciting antibodies (polyclonal and monoclonal) specific for the herbicide
      atrazine, the antibiotic sulfasalazine, and the vitamin biotin in mice and
      rabbits. The particles play the role of carrier and adjuvant, with the immune
      response being dependent on size and crystallinity. The affinity constants of the
      antibodies are similar to those reached with traditional immunization strategies
      based on the use of carrier proteins. This approach has not been previously
      described, being of scientific and practical interest, as it can lead to
      immunogens safer than the conventional ones, potentially applicable to human
      vaccination. In addition, the useful advantages of this technique include the
      stability of the metallic particles, the synthesis of immunogens in organic
      media, the versatility of particle derivatization, the ease of purification, the
      full chemical characterization of immunogens, the lack of a requirement for an
      adjuvant, the reduction of the cross reactivity, and the low cost of materials.
      Also, the analytical performances of the immunoassays developed using these
      antibodies are comparable to those obtained by the standard protocols. Analytical
      applications of the developed ELISAs were fully demonstrated. Characterization
      (IgG nature, affinity constants, etc.) of the immunoreagents were also fully
      assessed.

PMID- 23005037
TI  - Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N
      glycosylation.
AB  - Degradation of the basement membrane by MMPs (matrix metalloproteinases) is one
      of the most critical steps in tumour progression. CD147 is a tumour-associated
      antigen that plays a key regulatory role for MMP activities. In the present
      study, mass spectrum analysis demonstrated that the purified native CD147 from
      human lung cancer tissue was N-glycosylated and contained a series of high
      mannose and complex-type N-linked glycan structures. Moreover, native
      glycosylated CD147 existed exclusively as oligomers in solution and directly
      stimulated MMP production more efficiently than non-glycosylated prokaryotic
      CD147. The glycosylation site mutation results indicated that, among three N
      glycan attachment sites, the N152Q mutants were retained in the endoplasmic
      reticulum and unfolded protein response signalling was activated. This improper
      intracellular accumulation impaired its MMP-inducing activity. Increased beta1,6
      branching of N-glycans as a result of overexpression of GnT-V (N
      acetylglucosaminyltransferase V) plays an important role in tumour metastasis. In
      the present study, we identified CD147 as a target protein of GnT-V and found
      that overexpression of GnT-V resulted in an elevated level of CD147 at the plasma
      membrane and in cell-conditioned medium, thereby increasing the induction of
      MMPs. The present study reveals the important role of N-glycosylation of CD147 in
      its biological function and implied that targeting aberrant beta1,6-branching of
      N-glycans on CD147 would be valuable for the development of novel therapeutic
      modalities against carcinoma.

PMID- 23005038
TI  - Distribution of fluconazole-resistant Candida bloodstream isolates among
      hospitals and inpatient services in Israel.
AB  - The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is
      known about susceptibility patterns in different nosocomial settings. We
      prospectively analysed Candida bloodstream isolates in 18 medical centres in
      Israel (six tertiary-care and 12 community hospitals). The study included 444
      episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole
      resistant). Institutional FRC bloodstream infection rates correlated with annual
      inpatient days, and were strongly associated with the presence and activity of
      haematology/oncology services. Infection with Candida krusei and fluconazole
      resistant Candida glabrata occurred exclusively in hospitals with >600 beds.
      These findings suggest that empirical antifungal strategies should be tailored to
      the nosocomial setting. 

PMID- 23005039
TI  - Melatonin treatment effects on adolescent students' sleep timing and sleepiness
      in a placebo-controlled crossover study.
AB  - During the last few decades, the incidence of sleep-onset insomnia, due to delay
      of circadian phase, has increased substantially among adolescents all over the
      world. We wanted to investigate whether a small dose of melatonin given daily,
      administered in the afternoon, could advance the sleep timing in teenagers.
      Twenty-one students, aged 14-19 yrs, with sleep-onset difficulties during school
      weeks were recruited. The study was a randomized, double blind, placebo (PL)
      controlled crossover trial, lasting 5 wks. During the first 6 d in wks 2 and 4,
      the students received either PL or melatonin (1 mg) capsules between 16:30 and
      18:00 h. During the first 6 d of wk 5, all students received melatonin. Wks 1 and
      3 were capsule-free. In the last evening of each week and the following morning,
      the students produced saliva samples at home for later melatonin analysis. The
      samples were produced the same time each week, as late as possible in the evening
      and as early as possible in the morning. Both the student and one parent received
      automatic mobile text messages 15 min before saliva sampling times and capsule
      intake at agreed times. Diaries with registration of presumed sleep, subjective
      sleepiness during the day (Karolinska Sleepiness Scale, KSS) and times for
      capsule intake and saliva samplings were completed each day. Primary analysis
      over 5 wks gave significant results for melatonin, sleep and KSS. Post hoc
      analysis showed that reported sleep-onset times were advanced after melatonin
      school weeks compared with PL school weeks (p < .005) and that sleep length was
      longer (p < .05). After the last melatonin school week, the students fell asleep
      68 min earlier and slept 62 min longer each night compared with the baseline
      week. Morning melatonin values in saliva diminished compared with PL (p < .001)
      and evening values increased (p < .001), indicating a possible sleep phase
      advance. Compared with PL school weeks, the students reported less wake up (p <
      .05), less school daytime sleepiness (p < .05) and increased evening sleepiness
      (p < .005) during melatonin weeks. We conclude that a small dose of melatonin
      given daily, administered in the afternoon, could advance the sleep timing and
      make the students more alert during school days even if they continued their
      often irregular sleep habits during weekends.

PMID- 23005041
TI  - Physician preferences for medication attributes for the prophylactic treatment of
      patients with severe haemophilia A with inhibitors to factor VIII.
AB  - Prophylaxis may be beneficial for patients with severe haemophilia A who have
      developed inhibitors to factor VIII. The aim of this study was to determine
      physicians' preferences for medication attributes in the prophylactic treatment
      of this patient population. Haematologists from Europe (EU) and the United States
      (US) participated in a discrete choice exercise to explore their preferences for
      medication attributes (efficacy, cost, scientific evidence, dosing frequency and
      administration time) associated with prophylaxis for severe haemophilia A in
      patients with inhibitors to factor VIII. Physicians' preferences for medication
      attributes were assessed through completion of 25 trade-off tasks that included a
      choice between two hypothetical medications each comprised of one randomized
      level of each medication attribute. Participants also completed a
      sociodemographic questionnaire. Data were analysed using a random effects logit
      model. Participants (N = 36: US = 19; EU = 17) were 80.6% men, had a mean of 19.8
      years (SD +/- 8.1) [range 6-35] of practice experience. The physicians treated an
      average of 5.7 (+/- 5.5) patients with severe haemophilia A and inhibitors per
      month and reported treating 36.2% of these patients prophylactically. The most
      important medication attributes for prophylactic treatment were efficacy
      [Relative Importance (RI) = 35.0%] and scientific evidence (RI = 34.1%), whereas
      treatment cost (12.0%), dosing frequency (10.8%) and administration time (8.2%)
      were less important. Results were similar across the EU and US. Efficacy and
      scientific evidence are the primary considerations for physicians' choice of
      prophylactic medications for use in this patient population.

PMID- 23005040
TI  - Aberrant promoter methylation of Dab2 gene in myelodysplastic syndrome.
AB  - OBJECTIVES: Human Disabled-2 (Dab2), a putative tumor suppressor gene, is
      frequently down-regulated in human tumors. This study aims to explore the
      association between Dab2 methylation status and expression in newly diagnosed
      myelodysplastic syndrome (MDS) patients and patients who received 5-aza-2'
      deoxycytidine (decitabine) treatment, so as to determine the effect of Dab2 in
      the pathogenesis of MDS. METHODS: Methylation-specific polymerase chain reaction
      and bisulfite sequencing were used to detect the methylation status of Dab2 gene.
      Dab2 expression was investigated by using fluorescence quantitation RT-PCR (FQRT
      PCR) and western blot analysis. RESULTS: Hypermethylation of Dab2 gene was
      present in 50.6% of patients with MDS and was significantly correlated with the
      down-regulation of Dab2 mRNA and protein expression. There was a significant
      difference in methylation frequency between refractory anemia/refractory anemia
      with ringed sideroblasts/MDS associated with isolated del (5q) (RA/RARS/5q-)
      group (33.3%) and refractory anemia with excess blasts-1/-2 (RAEB-1/RAEB-2) group
      (73.3%). Significant difference was also observed between refractory cytopenia
      with multiline dysplasia group (37.8%) and RAEB-1/RAEB-2 group. In addition,
      higher frequency of hypermethylation was observed in intermediate-2-/high-risk
      group, compared to low-risk/intermediate-1-risk group (75.0% vs. 40.0%).
      Demethylating agent 5-aza-2'-deoxycytidine treatment could partly reverse
      hypermethylation and, hence, restore the expression of Dab2 gene. CONCLUSIONS:
      The Dab2 gene is inactivated in MDS in part by DNA methylation, and the
      suppression of Dab2 expression by DNA methylation may play a role in the
      development of MDS.

PMID- 23005042
TI  - Thermalization of interacting fermions and delocalization in Fock space.
AB  - We investigate the onset of "eigenstate thermalization" and the crossover to
      ergodicity in a system of one-dimensional fermions with increasing interaction.
      We analyze the fluctuations in the expectation values of most relevant few-body
      operators with respect to eigenstates. It turns out that these are intimately
      related to the inverse participation ratio of eigenstates displayed in the
      operator eigenbasis. Based on this observation, we find good evidence that
      eigenstate thermalization should set in even for vanishingly small perturbations
      in the thermodynamic limit.

PMID- 23005043
TI  - Normal heat conduction in one-dimensional momentum conserving lattices with
      asymmetric interactions.
AB  - We study heat conduction behavior of one-dimensional lattices with asymmetric,
      momentum conserving interparticle interactions. We find that with a certain
      degree of interaction asymmetry, the heat conductivity measured in nonequilibrium
      stationary states converges in the thermodynamical limit. Our analysis suggests
      that the mass gradient resulting from asymmetric interactions may provide a
      phonon scattering mechanism in addition to that caused by nonlinear interactions.

PMID- 23005044
TI  - Compact waves in microscopic nonlinear diffusion.
AB  - We analyze the spread of a localized peak of energy into vacuum for nonlinear
      diffusive processes. In contrast with standard diffusion, the nonlinearity
      results in a compact wave with a sharp front separating the perturbed region from
      vacuum. In d spatial dimensions, the front advances as t^{1/(2+da)} according to
      hydrodynamics, with a the nonlinearity exponent. We show that fluctuations in the
      front position grow as ~t^{MU}eta, where MU<1/2+da is an exponent that we measure
      and eta is a random variable whose distribution we characterize. Fluctuating
      corrections to hydrodynamic profiles give rise to an excess penetration into
      vacuum, revealing scaling behaviors and robust features. We also examine the
      discharge of a nonlinear rarefaction wave into vacuum. Our results suggest the
      existence of universal scaling behaviors at the fluctuating level in nonlinear
      diffusion.

PMID- 23005045
TI  - Effects of phase disorder on transport of globally coupled Brownian motors.
AB  - The transport of N globally coupled Brownian motors driven by a periodic force
      with phase disorder is investigated. An approximate theoretical analysis of the
      model is presented. The effects of the phase disorder and the driving strength of
      the periodic force on the transport of the coupled Brownian motors are discussed
      both theoretically and numerically. It is found that the increase of the
      periodical driving force decreases the average velocity, while the coupled
      particles may benefit from the phase disorder to enhance collective transport.

PMID- 23004964
TI  - Search for dark matter and large extra dimensions in pp collisions yielding a
      photon and missing transverse energy.
AB  - Results are presented from a search for new physics in the final state containing
      a photon (gamma) and missing transverse energy (E[combininb /](T)). The data
      correspond to an integrated luminosity of 5.0 fb(-1) collected in pp collisions
      at ?[s]=7 TeV by the CMS experiment. The observed event yield agrees with
      standard-model expectations for the gamma+E[combininb /](T) events. Using models
      for the production of dark-matter particles (chi), we set 90% confidence level
      (C.L.) upper limits of 13.6-15.4 fb on chi production in the gamma+E[combininb
      /](T) state. These provide the most sensitive upper limits for spin-dependent chi
      nucleon scattering for chi masses (M(chi)) between 1 and 100 GeV. For spin
      independent contributions, the present limits are extended to M(chi)<3.5 GeV. For
      models with 3-6 large extra dimensions, our data exclude extra-dimensional Planck
      scales between 1.64 and 1.73 TeV at 95% C.L.

PMID- 23005046
TI  - First-principles derivation of static avalanche-size distributions.
AB  - We study the energy minimization problem for an elastic interface in a random
      potential plus a quadratic well. As the position of the well is varied, the
      ground state undergoes jumps, called shocks or static avalanches. We introduce an
      efficient and systematic method to compute the statistics of avalanche sizes and
      manifold displacements. The tree-level calculation, i.e., mean-field limit, is
      obtained by solving a saddle-point equation. Graphically, it can be interpreted
      as the sum of all tree graphs. The 1-loop corrections are computed using results
      from the functional renormalization group. At the upper critical dimension the
      shock statistics is described by the Brownian force model (BFM), the static
      version of the so-called Alessandro-Beatrice-Bertotti-Montorsi (ABBM) model in
      the nonequilibrium context of depinning. This model can itself be treated exactly
      in any dimension and its shock statistics is that of a Levy process. Contact is
      made with classical results in probability theory on the Burgers equation with
      Brownian initial conditions. In particular we obtain a functional extension of an
      evolution equation introduced by Carraro and Duchon, which recursively constructs
      the tree diagrams in the field theory.

PMID- 23005047
TI  - Energy-landscape analysis of the two-dimensional nearest-neighbor phi4 model.
AB  - The stationary points of the potential energy function of the phi4 model on a two
      dimensional square lattice with nearest-neighbor interactions are studied by
      means of two numerical methods: a numerical homotopy continuation method and a
      globally convergent Newton-Raphson method. We analyze the properties of the
      stationary points, in particular with respect to a number of quantities that have
      been conjectured to display signatures of the thermodynamic phase transition of
      the model. Although no such signatures are found for the nearest-neighbor phi4
      model, our study illustrates the strengths and weaknesses of the numerical
      methods employed.

PMID- 23005048
TI  - Computational study of a multistep height model.
AB  - An equilibrium random surface multistep height model proposed in [Abraham and
      Newman, EPL 86, 16002 (2009)] is studied using a variant of the worm algorithm.
      In one limit, the model reduces to the two-dimensional Ising model in the height
      representation. When the Ising model constraint of single height steps is
      relaxed, the critical temperature and critical exponents are continuously varying
      functions of the parameter controlling height steps larger than one. Numerical
      estimates of the critical exponents can be mapped via a single parameter, the
      Coulomb gas coupling, to the exponents of the O(n) loop model on the honeycomb
      lattice with n <= 1.

PMID- 23005049
TI  - Caloric curve of star clusters.
AB  - Self-gravitating systems, such as globular clusters or elliptical galaxies, are
      the prototypes of many-body systems with long-range interactions, and should be
      the natural arena in which to test theoretical predictions on the statistical
      behavior of long-range-interacting systems. Systems of classical self-gravitating
      particles can be studied with the standard tools of equilibrium statistical
      mechanics, provided the potential is regularized at small length scales and the
      system is confined in a box. The confinement condition looks rather unphysical in
      general, so that it is natural to ask whether what we learn with these studies is
      relevant to real self-gravitating systems. In order to provide an answer to this
      question, we consider a basic, simple, yet effective model of globular clusters:
      the King model. This model describes a self-consistently confined system, without
      the need of any external box, but the stationary state is a nonthermal one. In
      particular, we consider the King model with a short-distance cutoff on the
      interactions, and we discuss how such a cutoff affects the caloric curve, i.e.,
      the relation between temperature and energy. We find that the cutoff stabilizes a
      low-energy phase, which is absent in the King model without cutoff; the caloric
      curve of the model with cutoff turns out to be very similar to that of previously
      studied confined and regularized models, but for the absence of a high-energy
      gaslike phase. We briefly discuss the possible phenomenological as well as
      theoretical implications of these results.

PMID- 23005050
TI  - Universality aspects of the d = 3 random-bond Blume-Capel model.
AB  - The effects of bond randomness on the universality aspects of the simple cubic
      lattice ferromagnetic Blume-Capel model are discussed. The system is studied
      numerically in both its first- and second-order phase transition regimes by a
      comprehensive finite-size scaling analysis. We find that our data for the second
      order phase transition, emerging under random bonds from the second-order regime
      of the pure model, are compatible with the universality class of the 3d random
      Ising model. Furthermore, we find evidence that the second-order transition
      emerging under bond randomness from the first-order regime of the pure model
      belongs to a new and distinctive universality class. The first finding reinforces
      the scenario of a single universality class for the 3d Ising model with the three
      well-known types of quenched uncorrelated disorder (bond randomness, site and
      bond dilution). The second amounts to a strong violation of the universality
      principle of critical phenomena. For this case of the ex-first-order 3d Blume
      Capel model, we find sharp differences from the critical behaviors, emerging
      under randomness, in the cases of the ex-first-order transitions of the
      corresponding weak and strong first-order transitions in the 3d three-state and
      four-state Potts models.

PMID- 23005051
TI  - General expression for entropy production in transport processes based on the
      thermomass model.
AB  - The entropy production in classical irreversible thermodynamics is expressed as a
      bilinear form of generalized (driving) forces and conjugated (driven) fluxes,
      which suffers from the arbitrary decomposition of the forces and the fluxes, and
      the possible negative entropy production in non-Fourier heat conduction problems
      (heat waves). This paper presents a general form of the entropy production for
      heat conduction based on the thermomass model, which is the product of the
      friction force and the drift velocity of the thermomass divided by the
      temperature; it holds true for both Fourier and non-Fourier heat conduction. Then
      a generalization of the entropy production is given for other kinds of linear and
      nonlinear transport processes. The general expression for entropy production is
      consistent with that given by extended irreversible thermodynamics, where the
      system entropy depends not only on the classical variables, but also on the
      dissipative fluxes, for example, the heat flux in heat conduction problems.

PMID- 23005052
TI  - Ordered packing of elastic wires in a sphere.
AB  - In this paper we study the ordered packing of wires in a sphere. We propose an
      analytical model and compare the model predictions with the results of our
      experiments and simulations for the maximum packing fraction, the number of
      formed coils, the fractal dimension, and bending energy. We show that the
      relative system size [i.e., the ratio of the wire radius to the sphere radius
      (a/R)] is the most important control parameter for the maximum packing fraction.
      We find that the number of coils obeys a power-law relation of the form
      N~(R/a){1.5} and the fractal dimension of the structures is 2.5, independent of
      the system size. Our theoretical results are in good agreement with the
      experimental data and the predictions of the numerical simulations.

PMID- 23005053
TI  - Supersymmetric extension of the quantum spherical model.
AB  - In this work, we present a supersymmetric extension of the quantum spherical
      model, both in components and also in the superspace formalisms. We find the
      solution for short- and long-range interactions through the imaginary time
      formalism path integral approach. The existence of critical points (classical and
      quantum) is analyzed and the corresponding critical dimensions are determined.

PMID- 23005054
TI  - Continuous percolation phase transitions of random networks under a generalized
      Achlioptas process.
AB  - Using finite-size scaling, we have investigated the percolation phase transitions
      of evolving random networks under a generalized Achlioptas process (GAP). During
      this GAP, the edge with a minimum product of two connecting cluster sizes is
      taken with a probability p from two randomly chosen edges. This model becomes the
      Erdos-Renyi network at p=0.5 and the random network under the Achlioptas process
      at p=1. Using both the fixed point of the size ratio s{2}/s{1} and the straight
      line of lns{1}, where s{1} and s{2} are the reduced sizes of the largest and the
      second-largest cluster, we demonstrate that the phase transitions of this model
      are continuous for 0.5 <= p <= 1. From the slopes of lns{1} and ln(s{2}/s{1})' at
      the critical point, we get critical exponents beta and nu of the phase
      transitions. At 0.5 <= p <= 0.8, it is found that beta, nu, and s{2}/s{1} at
      critical point are unchanged and the phase transitions belong to the same
      universality class. When p >= 0.9, beta, nu, and s{2}/s{1} at critical point vary
      with p and the universality class of phase transitions depends on p.

PMID- 23005055
TI  - Single-file diffusion of particles in a box: transient behaviors.
AB  - We consider a finite number of particles with soft-core interactions, subjected
      to thermal fluctuations and confined in a box with excluded mutual passage. Using
      numerical simulations, we focus on the influence of the longitudinal confinement
      on the transient behavior of the longitudinal mean squared displacement. We
      exhibit several power laws for its time evolution according to the confinement
      range and to the rank of the particle in the file. We model the fluctuations of
      the particles as those of a chain of springs and point masses in a thermal bath.
      Our main conclusion is that actual system dynamics can be described in terms of
      the normal oscillation modes of this chain. Moreover, we obtain complete
      expressions for the physical observables, in excellent agreement with our
      simulations. The correct power laws for the time dependency of the mean squared
      displacement in the various regimes are recovered, and analytical expressions of
      the prefactors according to the relevant parameters are given.

PMID- 23005056
TI  - Heat current limiter and constant heat current source.
AB  - Current limiters and constant current sources, which play important roles in
      electronic circuits, have been built up for many decades. Their thermal
      counterparts, heat current limiters and constant heat current sources, are still
      not available yet. By combining two typical nonlinear lattices, the Frenkel
      Kontorova (FK) lattice and a coupled rotator lattice, together, we present by
      numerical simulation a model that displays complete negative differential thermal
      resistance (NDTR). Namely, in a wide regime, the heat current that flows through
      this model is always a decreasing function of the temperature drop applied to it,
      no matter whether the change in the temperature drop is due to a change in the
      high or the low temperature. We show that, upon being properly set up, a complete
      NDTR can work as either a heat current limiter or a constant heat current source.

PMID- 23005057
TI  - Superconductor-insulator transition on annealed complex networks.
AB  - Cuprates show multiphase and multiscale complexity that has hindered physicists
      search for the mechanism of high T{c} for many years. Recently the interest has
      been addressed to a possible optimum inhomogeneity of dopants, defects, and
      interstitials, and the structural scale invariance of dopants detected by
      scanning micro-x-ray diffraction has been reported to promote the critical
      temperature. In order to shed light on critical phenomena on granular materials,
      here we propose a stylized model capturing the essential characteristics of the
      superconducting-insulator transition of a highly dynamical, heterogeneous
      granular material: the random transverse Ising model (RTIM) on annealed complex
      network. We show that when the networks encode for high heterogeneity of the
      expected degrees described by a power-law distribution, the critical temperature
      for the onset of the superconducting phase diverges to infinity as the power-law
      exponent gamma of the expected degree distribution is less than 3, i.e., gamma<3.
      Moreover we investigate the case in which the critical state of the electronic
      background is triggered by an external parameter g that determines an exponential
      cutoff in the power-law expected degree distribution characterized by an exponent
      gamma. We find that for g=g{c} the critical temperature for the superconducting
      insulator transition has a maximum if gamma>3 and diverges if gamma<3.

PMID- 23005058
TI  - Power spectrum of mass and activity fluctuations in a sandpile.
AB  - We consider a directed Abelian sandpile on a strip of size 2*n, driven by adding
      a grain randomly at the left boundary after every T timesteps. We establish the
      exact equivalence of the problem of mass fluctuations in the steady state and the
      number of zeros in the ternary-base representation of the position of a random
      walker on a ring of size 3^{n}. We find that while the fluctuations of mass have
      a power spectrum that varies as 1/f for frequencies in the range 3^{-2n}?f?1/T,
      the activity fluctuations in the same frequency range have a power spectrum that
      is linear in f.

PMID- 23005059
TI  - Linear response theory in the Vlasov equation for homogeneous and for
      inhomogeneous quasistationary states.
AB  - Response to small external forces is investigated in quasistationary states of
      Hamiltonian systems having long-range interactions. Quasistationary states are
      recognized as stable stationary solutions to the Vlasov equation, and, hence, the
      linear response theory to the Vlasov equation is proposed for spatially one
      dimensional systems with periodic boundary condition. The proposed theory is
      applicable both to homogeneous and to inhomogeneous quasistationary states and is
      demonstrated in the Hamiltonian mean-field model. In the homogeneous case
      magnetic susceptibility is explicitly obtained, and the Curie-Weiss like law is
      suggested in a high-energy region. The linear response is also computed in the
      inhomogeneous case, and resonance absorption is investigated to extract
      nonequilibrium dynamics in the unforced system. Theoretical predictions are
      examined by direct numerical simulations of the Vlasov equation.

PMID- 23005060
TI  - Distribution of velocities and acceleration for a particle in Brownian correlated
      disorder: inertial case.
AB  - We study the motion of an elastic object driven in a disordered environment in
      presence of both dissipation and inertia. We consider random forces with the
      statistics of random walks and reduce the problem to a single degree of freedom.
      It is the extension of the mean-field Alessandro-Beatrice- Bertotti-Montorsi
      (ABBM) model in presence of an inertial mass m. While the ABBM model can be
      solved exactly, its extension to inertia exhibits complicated history dependence
      due to oscillations and backward motion. The characteristic scales for avalanche
      motion are studied from numerics and qualitative arguments. To make analytical
      progress, we consider two variants which coincide with the original model
      whenever the particle moves only forward. Using a combination of analytical and
      numerical methods together with simulations, we characterize the distributions of
      instantaneous acceleration and velocity, and compare them in these three models.
      We show that for large driving velocity, all three models share the same large
      deviation function for positive velocities, which is obtained analytically for
      small and large m, as well as for m=6/25. The effect of small additional thermal
      and quantum fluctuations can be treated within an approximate method.

PMID- 23005061
TI  - Percolation in random sequential adsorption of extended objects on a triangular
      lattice.
AB  - The percolation aspect of random sequential adsorption of extended objects on a
      triangular lattice is studied by means of Monte Carlo simulations. The depositing
      objects are formed by self-avoiding lattice steps on the lattice. Jamming
      coverage theta{jam}, percolation threshold theta{p}, and their ratio
      theta{p}/theta{jam} are determined for objects of various shapes and sizes. We
      find that the percolation threshold theta{p} may decrease or increase with the
      object size, depending on the local geometry of the objects. We demonstrate that
      for various objects of the same length, the threshold theta{p} of more compact
      shapes exceeds the theta{p} of elongated ones. In addition, we study polydisperse
      mixtures in which the size of line segments making up the mixture gradually
      increases with the number of components. It is found that the percolation
      threshold decreases, while the jamming coverage increases, with the number of
      components in the mixture.

PMID- 23005062
TI  - Surface scaling properties of decagonal quasicrystals under nonequilibrium
      vertical growth.
AB  - Restricted solid-on-solid (RSOS) growth models are studied on two different
      decagonal quasicrystal lattices, namely the Penrose tiling lattice and the random
      tiling lattice. There exist two types of growth blocks-fat and skinny tiles-which
      may have different sticking probabilities. We found that the RSOS growths on both
      lattices belong to the Kardar-Parisi-Zhang universality class when they have the
      same sticking probabilities in spite of the lack of periodicity in the
      substrates. However, when they have tile-type dependent sticking probabilities,
      the RSOS models on two lattices may produce different scaling behaviors. Growth
      on Penrose tiling shows that the roughness exponent is around 0.4 while that on
      random tiling is around 0.49. Our observation may provide an effective way to
      investigate the bulk structures of decagonal quasicrystals.

PMID- 23005063
TI  - Spectral fluctuation and 1/falpha noise in the energy level statistics of
      interacting trapped bosons.
AB  - It has been recently shown numerically that the transition from integrability to
      chaos in quantum systems and the corresponding spectral fluctuations are
      characterized by 1/f^{alpha} noise with 1<=alpha<=2. The system of interacting
      trapped bosons is inhomogeneous and complex. The presence of an external harmonic
      trap makes it more interesting as, in the atomic trap, the bosons occupy partly
      degenerate single-particle states. Earlier theoretical and experimental results
      show that at zero temperature the low-lying levels are of a collective nature and
      high-lying excitations are of a single-particle nature. We observe that for few
      bosons, the P(s) distribution shows the Shnirelman peak, which exhibits a large
      number of quasidegenerate states. For a large number of bosons the low-lying
      levels are strongly affected by the interatomic interaction, and the
      corresponding level fluctuation shows a transition to a Wigner distribution with
      an increase in particle number. It does not follow Gaussian orthogonal ensemble
      random matrix predictions. For high-lying levels we observe the uncorrelated
      Poisson distribution. Thus it may be a very realistic system to prove that
      1/f^{alpha} noise is ubiquitous in nature.

PMID- 23005064
TI  - Hierarchical maximum entropy principle for generalized superstatistical systems
      and Bose-Einstein condensation of light.
AB  - A principle of hierarchical entropy maximization is proposed for generalized
      superstatistical systems, which are characterized by the existence of three
      levels of dynamics. If a generalized superstatistical system comprises a set of
      superstatistical subsystems, each made up of a set of cells, then the Boltzmann
      Gibbs-Shannon entropy should be maximized first for each cell, second for each
      subsystem, and finally for the whole system. Hierarchical entropy maximization
      naturally reflects the sufficient time-scale separation between different
      dynamical levels and allows one to find the distribution of both the intensive
      parameter and the control parameter for the corresponding superstatistics. The
      hierarchical maximum entropy principle is applied to fluctuations of the photon
      Bose-Einstein condensate in a dye microcavity. This principle provides an
      alternative to the master equation approach recently applied to this problem. The
      possibility of constructing generalized superstatistics based on a statistics
      different from the Boltzmann-Gibbs statistics is pointed out.

PMID- 23005065
TI  - Evolution of optimal Levy-flight strategies in human mental searches.
AB  - Recent analysis of empirical data [Radicchi, Baronchelli, and Amaral, PloS ONE 7,
      e029910 (2012)] showed that humans adopt Levy-flight strategies when exploring
      the bid space in online auctions. A game theoretical model proved that the
      observed Levy exponents are nearly optimal, being close to the exponent value
      that guarantees the maximal economical return to players. Here, we rationalize
      these findings by adopting an evolutionary perspective. We show that a simple
      evolutionary process is able to account for the empirical measurements with the
      only assumption that the reproductive fitness of the players is proportional to
      their search ability. Contrary to previous modeling, our approach describes the
      emergence of the observed exponent without resorting to any strong assumptions on
      the initial searching strategies. Our results generalize earlier research, and
      open novel questions in cognitive, behavioral, and evolutionary sciences.

PMID- 23005066
TI  - Effect of particle polydispersity on the irreversible adsorption of fine
      particles on patterned substrates.
AB  - We performed extensive Monte Carlo simulations of the irreversible adsorption of
      polydispersed disks inside the cells of a patterned substrate. The model captures
      relevant features of the irreversible adsorption of spherical colloidal particles
      on patterned substrates. The pattern consists of (equal) square cells, where
      adsorption can take place, centered at the vertices of a square lattice. Two
      independent, dimensionless parameters are required to control the geometry of the
      pattern, namely, the cell size and cell-cell distance, measured in terms of the
      average particle diameter. However, to describe the phase diagram, two additional
      dimensionless parameters, i.e., the minimum and maximum particle radii, are also
      required. We find that the transition between any two adjacent regions of the
      phase diagram solely depends on the largest and smallest particle sizes, but not
      on the shape of the distribution function of the radii. We consider size
      dispersions up to 20% of the average radius using a physically motivated,
      truncated, Gaussian-size distribution, and focus on the regime where adsorbing
      particles do not interact with those previously adsorbed on neighboring cells to
      characterize the jammed state structure. The study generalizes previous exact
      relations on monodisperse particles to account for size dispersion. Due to the
      presence of the pattern, the coverage shows a nonmonotonic dependence on the cell
      size. The pattern also affects the radius of adsorbed particles, where one
      observes preferential adsorption of smaller radii, particularly at high
      polydispersity.

PMID- 23005067
TI  - Geometrical frustration of an extended Hubbard diamond chain in the quasiatomic
      limit.
AB  - We study the geometrical frustration of an extended Hubbard model on a diamond
      chain, where vertical lines correspond to the hopping and repulsive Coulomb
      interaction terms between sites while the remaining lines represent only the
      Coulomb repulsion term. The phase diagrams at zero temperature show quite curious
      phases: five types of frustrated states and four types of nonfrustrated states,
      ordered antiferromagnetically. Although a decoration transformation was derived
      for spin-coupling systems, this approach can be applied to electron-coupling
      systems. Thus the extended Hubbard model can be mapped onto another effective
      extended Hubbard model in the atomic limit with additional three- and four-body
      couplings. This effective model is solved exactly using the transfer-matrix
      method. In addition, using the exact solution of this model, we discuss several
      thermodynamic properties away from the half-filled band, such as chemical
      potential behavior, electronic density, and entropy, for which we study
      geometrical frustration. Consequently, we investigate the specific heat as well.

PMID- 23005068
TI  - Zon-Cohen singularity and negative inverse temperature in a trapped-particle
      limit.
AB  - We study a Brownian particle on a moving periodic potential. We focus on the
      statistical properties of the work done by the potential and the heat dissipated
      by the particle. When the period and the depth of the potential are both large,
      by using a boundary layer analysis, we calculate a cumulant generating function
      and a biased distribution function. The result allows us to understand a Zon
      Cohen singularity for an extended fluctuation theorem from a viewpoint of rare
      trajectories characterized by a negative inverse temperature of the biased
      distribution function.

PMID- 23005069
TI  - Resonance dynamics evoked via noise recycling procedure.
AB  - We study the effect of noise recycling on nonequilibrium escape dynamics in a
      bistable system. For small noise, the non-Markovian problem is reduced to a two
      state model with the master equation depending on not only the current state but
      also the earlier state, based on which we are able to derive the analytical
      formulas for the switching rate, the autocorrelation function, and the power
      spectrum density (PSD). Both the theoretical and the numerical results show that,
      with modulating the time delay in noise recycling, a monotonic PSD may switch to
      a nonmonotonic one; the amplitude of PSD at resonance frequency exhibits a
      pronounced maximum at a certain noise level, declaring the onset of stochastic
      resonance (SR) in the absence of a weak periodic signal. Further, we also
      demonstrate that the linear response to the external periodic force displays a
      maximum at a certain level of time delay, displaying the signature of SR.

PMID- 23005070
TI  - Quantum refrigerators and the third law of thermodynamics.
AB  - The rate of temperature decrease of a cooled quantum bath is studied as its
      temperature is reduced to absolute zero. The third law of thermodynamics is then
      quantified dynamically by evaluating the characteristic exponent zeta of the
      cooling process dT(t)/dt~-T^{zeta} when approaching absolute zero, T->0. A
      continuous model of a quantum refrigerator is employed consisting of a working
      medium composed either by two coupled harmonic oscillators or two coupled two
      level systems. The refrigerator is a nonlinear device merging three currents from
      three heat baths: a cold bath to be cooled, a hot bath as an entropy sink, and a
      driving bath which is the source of cooling power. A heat-driven refrigerator
      (absorption refrigerator) is compared to a power-driven refrigerator. When
      optimized, both cases lead to the same exponent zeta, showing a lack of
      dependence on the form of the working medium and the characteristics of the
      drivers. The characteristic exponent is therefore determined by the properties of
      the cold reservoir and its interaction with the system. Two generic heat bath
      models are considered: a bath composed of harmonic oscillators and a bath
      composed of ideal Bose/Fermi gas. The restrictions on the interaction Hamiltonian
      imposed by the third law are discussed. In the Appendices, the theory of
      periodically driven open systems and its implication for thermodynamics are
      outlined.

PMID- 23005071
TI  - Nonequilibrium and information: the role of cross correlations.
AB  - We discuss the relevance of information contained in cross correlations among
      different degrees of freedom, which is crucial in nonequilibrium systems. In
      particular we consider a stochastic system where two degrees of freedom X{1} and
      X{2}-in contact with two different thermostats-are coupled together. The
      production of entropy and the violation of equilibrium fluctuation-dissipation
      theorem (FDT) are both related to the cross correlation between X{1} and X{2}.
      Information about such cross correlation may be lost when single-variable reduced
      models for X_{1} are considered. Two different procedures are typically applied:
      (a) one totally ignores the coupling with X{2}; and (b) one models the effect of
      X{2} as an average memory effect, obtaining a generalized Langevin equation. In
      case (a) discrepancies between the system and the model appear both in entropy
      production and linear response; the latter can be exploited to define effective
      temperatures, but those are meaningful only when time scales are well separated.
      In case (b) linear response of the model well reproduces that of the system;
      however the loss of information is reflected in a loss of entropy production.
      When only linear forces are present, such a reduction is dramatic and makes the
      average entropy production vanish, posing problems in interpreting FDT
      violations.

PMID- 23005072
TI  - Universal anomalous diffusion of weakly damped particles.
AB  - We show that anomalous diffusion arises in two different models for the motion of
      randomly forced and weakly damped particles: one is a generalization of the
      Ornstein-Uhlenbeck process with a random force, which depends on position as well
      as time, the other is a generalization of the Chandrasekhar-Rosenbluth model of
      stellar dynamics, encompassing non-Coulombic potentials. We show that both models
      exhibit anomalous diffusion of position x and momentum p with the same exponents:
      (x{2})~C{x}t{2} and (p{2})~C{p}t{2/5}. We are able to determine the prefactors
      C{x}, C{p} analytically.

PMID- 23005073
TI  - Analytical description of the quantum-mesoscopic-classical transition in systems
      with quasidiscrete environments.
AB  - We investigate the dynamic properties of inhomogeneous nanomaterials, which
      appear in analytical descriptions typically as a series of delta functions with
      corresponding Gibbs weights. We focus on observables relevant for transport
      theories of Josephson junction arrays and granular systems near the
      superconductor-insulator transition. Furthermore, our description applies to the
      theory of tunnel junctions exchanging energy with a "bath," the latter having a
      discrete spectrum. Using the matrix theta-function formalism, we find an
      analytical expression for the transport characteristics capturing the complete
      temperature-driven transition from the quantum to the classical regime.

PMID- 23005074
TI  - Wigner surmise for mixed symmetry classes in random matrix theory.
AB  - We consider the nearest-neighbor spacing distributions of mixed random matrix
      ensembles interpolating between different symmetry classes or between integrable
      and nonintegrable systems. We derive analytical formulas for the spacing
      distributions of 2*2 or 4*4 matrices and show numerically that they provide very
      good approximations for those of random matrices with large dimension. This
      generalizes the Wigner surmise, which is valid for pure ensembles that are
      recovered as limits of the mixed ensembles. We show how the coupling parameters
      of small and large matrices must be matched depending on the local eigenvalue
      density.

PMID- 23005075
TI  - Density of zeros of the ferromagnetic Ising model on a family of fractals.
AB  - We studied distribution of zeros of the partition function of the ferromagnetic
      Ising model near the Yang-Lee edge on a family of Sierpinski gasket lattices
      whose members are labeled by an integer b (2 <= b<infinity). The obtained exact
      results on the first seven members of this family show that, for b >= 4,
      associated correlation length diverges more slowly than any power law when
      distance deltah from the edge tends to zero,
      xi_{YL}~exp[ln(b)sqrt[|ln(deltah)|/ln(lambda{0})]], lambda{0} being a decreasing
      function of b. We suggest a possible scenario for the emergence of the usual
      power-law behavior in the limit of very large b when fractal lattices become
      almost compact.

PMID- 23005076
TI  - Dimer motion on a periodic substrate: spontaneous symmetry breaking and absolute
      negative mobility.
AB  - We consider two coupled particles moving along a periodic substrate potential
      with negligible inertia effects (overdamped limit). Even when the particles are
      identical and the substrate spatially symmetric, a sinusoidal external driving of
      appropriate amplitude and frequency may lead to spontaneous symmetry breaking in
      the form of a permanent directed motion of the dimer. Thermal noise restores
      ergodicity and thus zero net velocity, but entails arbitrarily fast diffusion of
      the dimer for sufficiently weak noise. Moreover, upon application of a static
      bias force, the dimer exhibits a motion opposite to that force (absolute negative
      mobility). The key requirement for all these effects is a nonconvex interaction
      potential of the two particles.

PMID- 23005077
TI  - Abelian Manna model in three dimensions and below.
AB  - The Abelian Manna model of self-organized criticality is studied on various three
      dimensional and fractal lattices. The exponents for avalanche size, duration, and
      area distribution of the model are obtained by using a high-accuracy moment
      analysis. Together with earlier results on lower-dimensional lattices, the
      present results reinforce the notion of universality below the upper critical
      dimension and allow us to determine the coefficients of an epsilon expansion. By
      rescaling the critical exponents by the lattice dimension and incorporating the
      random walker dimension, a remarkable relation is observed, satisfied by both
      regular and fractal lattices.

PMID- 23005078
TI  - Temperature-difference-driven mass transfer through the vapor from a cold to a
      warm liquid.
AB  - Irreversible thermodynamics provides interface conditions that yield temperature
      and chemical potential jumps at phase boundaries. The interfacial jumps allow
      unexpected transport phenomena, such as the inverted temperature profile [Pao,
      Phys. Fluids 14, 306 (1971)] and mass transfer from a cold to a warm liquid
      driven by a temperature difference across the vapor phase [Mills and Phillips,
      Chem. Phys. Lett. 372, 615 (2002)]. Careful evaluation of the thermodynamic laws
      has shown [Bedeaux et al., Physica A 169, 263 (1990)] that the inverted
      temperature profile is observed for processes with a high heat of vaporization.
      In this paper, we show that cold to warm mass transfer through the vapor from a
      cold to a warm liquid is only possible when the heat of evaporation is
      sufficiently small. A necessary criterium for the size of the mass transfer
      coefficient is given.

PMID- 23005079
TI  - Theory of molecular crowding in Brownian hard-sphere liquids.
AB  - We derive an analytical pair potential of mean force for Brownian molecules in
      the liquid state. Our approach accounts for many-particle correlations of
      crowding particles of the liquid and for diffusive transport across the spatially
      modulated local density of crowders in the dense environment. Focusing on the
      limit of equal-size particles, we show that this diffusive transport leads to
      additional density- and structure-dependent terms in the interaction potential
      and to a much stronger attraction (by a factor of ~4 at average volume fraction
      of crowders phi{0}=0.25) than in the standard depletion interaction where the
      diffusive effects are neglected. As an illustration of the theory, we use it to
      study the size of a polymer chain in a solution of inert crowders. Even in the
      case of an athermal background solvent, when a classical chain should be fully
      swollen, we find a sharp coil-globule transition of the ideal chain collapsing at
      a critical value of the crowder volume fraction phi{c}~0.145.

PMID- 23005080
TI  - Shock propagation in granular flow subjected to an external impact.
AB  - We analyze a recent experiment [Boudet, Cassagne, and Kellay, Phys. Rev. Lett.
      103, 224501 (2009)] in which the shock created by the impact of a steel ball on a
      flowing monolayer of glass beads is studied quantitatively. We argue that radial
      momentum is conserved in the process and hence show that in two dimensions the
      shock radius increases in time t as a power law t{1/3}. This is confirmed in
      event driven simulations of an inelastic hard sphere system. The experimental
      data are compared with the theoretical prediction and are shown to compare well
      at intermediate times. At long times the experimental data exhibit a crossover to
      a different scaling behavior. We attribute this to the problem becoming
      effectively three dimensional due to the accumulation of particles at the shock
      front and propose a simple hard sphere model that incorporates this effect.
      Simulations of this model capture the crossover seen in the experimental data.

PMID- 23005081
TI  - Separation patterns between Brazilian nut and reversed Brazilian nut of a binary
      granular system.
AB  - This paper studies the segregation behavior of binary granular particles with
      diameters at approximately 10:1 in a vertically vibrated container. An array of
      transitional separation patterns between reversed Brazilian nut (RBN) and
      Brazilian nut (BN) separations are observed, with their geometrical features
      carefully measured. The binary particle system develops into either a stable
      separation pattern when f and Gamma are relatively low or an oscillating pattern
      when f and Gamma are relatively high. We regard these patterns as different
      phases, in which the stable patterns can be divided into phases of RBN, RBN
      transitional (RBNT), BNT, and BN. A phase parameter lambda between-1 and 1 is
      defined to describe the separation patterns based on the mass center height
      difference in large and small particles. By drawing f-Gamma-lambda phase
      diagrams, the system's tendency toward BN separation was found to increase with f
      and decrease with Gamma. Furthermore, the range of the tendency toward BN
      separation expands when the size of small particles rises. As the total mass of
      the small particles increases, the system's tendency toward RBN separation is
      enhanced. Abnormal points are also observed in the stable phase regions, and the
      oscillating phase shifts among the four stable phases with time. These stable
      phases can be explained via an analysis of the distribution of the dissipation
      energy, whereas the mechanism of the oscillating phase remains to be discovered.

PMID- 23005082
TI  - Critical flow and clustering in a model of granular transport: the interplay
      between drift and antidiffusion.
AB  - We study the transport of granular matter through a staircaselike array of K
      vertically vibrated compartments. Given a constant inflow rate Q<Q{cr}(K) into
      the top compartment, a continuous particle flow establishes itself along the
      entire length of the system. However, as soon as Q grows beyond the critical
      value Q{cr}(K) the particles form a cluster and the flow comes to a halt.
      Interestingly, this clustering is preceded by a subcritical warning signal: for Q
      values just below Q{cr}(K) the density profile along the conveyor belt
      spontaneously develops a pattern in which the compartments are alternatingly
      densely and sparsely populated. In a previous paper [Kanellopoulos and van der
      Weele, Int. J. Bifurcation Chaos 21, 2305 (2011)] this pattern was shown to be
      the result of a period-doubling bifurcation. The present paper aims at
      unravelling the physical mechanism that lies at the basis of the pattern
      formation. To this end we study the continuum version of the same system,
      replacing the compartment number k=1,...,K by a continuous variable x. The
      dynamics of the system is now described (instead of by K coupled ordinary
      differential equations) by a single partial differential equation of the Fokker
      Planck type, with a drift and a diffusive term that both depend on the density.
      The drift term turns out to be responsible for the subcritical density
      oscillations, thereby paving the way for the eventual clustering which sets in
      when the diffusion coefficient becomes negative. The observed sequence of events
      in the granular transport system is thus explained as an interplay between drift
      and (anti)diffusion.

PMID- 23005083
TI  - Computer simulations of the collapse of columns formed by elongated grains.
AB  - A numerical investigation of the collapse of granular columns has been conducted.
      In particular, we address the effect of the grain shape on the properties of the
      collapse. We show that the final runout and height of the deposits scale as a
      power law of the initial aspect ratio of the column, a, independently of the
      elongation of the grains used. We describe this process in terms of an energy
      balance, and construct an "inertial number" that can be used to describe the flow
      in terms of a recently proposed granular rheology. We argue that an effective
      friction that results from this dimensionless quantity explains why the shape of
      the grains is irrelevant for the final properties of the collapse.

PMID- 23005084
TI  - Constraints and vibrations in static packings of ellipsoidal particles.
AB  - We numerically investigate the mechanical properties of static packings of
      frictionless ellipsoidal particles in two and three dimensions over a range of
      aspect ratio and compression Deltaphi. While amorphous packings of spherical
      particles at jamming onset (Deltaphi=0) are isostatic and possess the minimum
      contact number z_{iso} required for them to be collectively jammed, amorphous
      packings of ellipsoidal particles generally possess fewer contacts than expected
      for collective jamming (z<z_{iso}) from naive counting arguments, which assume
      that all contacts give rise to linearly independent constraints on interparticle
      separations. To understand this behavior, we decompose the dynamical matrix M=H-S
      for static packings of ellipsoidal particles into two important components: the
      stiffness H and stress S matrices. We find that the stiffness matrix possesses
      2N(z_{iso}-z) eigenmodes e[over ]_{0} with zero eigenvalues even at finite
      compression, where N is the number of particles. In addition, these modes e[over
      ]_{0} are nearly eigenvectors of the dynamical matrix with eigenvalues that scale
      as Deltaphi, and thus finite compression stabilizes packings of ellipsoidal
      particles. At jamming onset, the harmonic response of static packings of
      ellipsoidal particles vanishes, and the total potential energy scales as
      delta^{4} for perturbations by amplitude delta along these "quartic" modes,
      e[over ]_{0}. These findings illustrate the significant differences between
      static packings of spherical and ellipsoidal particles.

PMID- 23005085
TI  - Deformation field in indentation of a granular ensemble.
AB  - An experimental study has been made of the flow field in indentation of a model
      granular material. A granular ensemble composed of spherical sand particles with
      average size of 0.4 mm is indented with a flat ended punch under plane-strain
      conditions. The region around the indenter is imaged in situ using a high-speed
      charge-coupled device (CCD) imaging system. By applying a hybrid image analysis
      technique to image sequences of the indentation, flow parameters such as
      velocity, velocity gradient, and strain rate are measured at high resolution. The
      measurements have enabled characterization of the main features of the flow such
      as dead material zones, velocity jumps, localization of deformation, and regions
      of highly rotational flow resembling vortices. Implications for validation of
      theoretical analyses and applications are discussed.

PMID- 23005086
TI  - Calculations of the structure of basin volumes for mechanically stable packings.
AB  - Experimental and computational model systems composed of frictionless particles
      in a fixed geometry have a finite number of distinct mechanically stable (MS)
      packings. The frequency of occurrence for each MS packing is highly variable and
      depends strongly on preparation protocol. Despite intense work, it is extremely
      difficult to predict a priori the MS packing probabilities. We describe a novel
      computational method for calculating the volume and other geometrical properties
      of the "basin of attraction" for each MS packing. The basin of attraction for an
      MS packing contains all initial conditions in configuration space that map to
      that MS packing using a given preparation protocol. We find that the basin is a
      highly complex structure. For a compressive-quench-from-zero-density protocol, we
      show the existence of a small core volume of the basin around each MS packing for
      which all points map to that MS packing. However, in contrast to previous studies
      for supercooled liquids, glasses, and over-compressed jammed systems, we find
      that the MS packing probabilities are very weakly correlated with this core
      volume. Instead, MS packing probabilities obtained from compression protocols
      that use initially dilute configurations and do not allow particle overlaps
      (i.e., those relevant to granular media) are determined by complex geometric
      features of the basin of attraction that are distant from the MS packing. In
      particular, we find that the shape of the average basin profile function S(l),
      which gives the probability for a point on a hyperspherical shell a distance l
      from a given MS packing to map back to that packing, can be described by a Gamma
      distribution with a peak that increases as the system size increases and as the
      quench rate decreases. We find a simple model which predicts S(l) for the extreme
      cases of very slow and fast quench rates.

PMID- 23005087
TI  - Nonequilibrium thermodynamics in sheared hard-sphere materials.
AB  - We combine the shear-transformation-zone (STZ) theory of amorphous plasticity
      with Edwards' statistical theory of granular materials to describe shear flow in
      a disordered system of thermalized hard spheres. The equations of motion for this
      system are developed within a statistical thermodynamic framework analogous to
      that which has been used in the analysis of molecular glasses. For hard spheres,
      the system volume V replaces the internal energy U as a function of entropy S in
      conventional statistical mechanics. In place of the effective temperature, the
      compactivity X=?V/?S characterizes the internal state of disorder. We derive the
      STZ equations of motion for a granular material accordingly, and predict the
      strain rate as a function of the ratio of the shear stress to the pressure for
      different values of a dimensionless, temperature-like variable near a jamming
      transition. We use a simplified version of our theory to interpret numerical
      simulations by Haxton, Schmiedeberg, and Liu, and in this way are able to obtain
      useful insights about internal rate factors and relations between jamming and
      glass transitions.

PMID- 23004965
TI  - Search for supersymmetry in events with three leptons and missing transverse
      momentum in ?[s]=7 TeV pp collisions with the ATLAS detector.
AB  - A search for the weak production of charginos and neutralinos decaying to a final
      state with three leptons (electrons or muons) and missing transverse momentum is
      presented. The analysis uses 2.06 fb(-1) of ?[s]=7 TeV proton-proton collision
      data delivered by the Large Hadron Collider and recorded with the ATLAS detector.
      Observations are consistent with standard model expectations in two signal
      regions that are either depleted or enriched in Z-boson decays. Upper limits at
      95% confidence level are set in R-parity conserving phenomenological minimal
      supersymmetric and simplified models. For the simplified models, degenerate
      lightest chargino and next-to-lightest neutralino masses up to 300 GeV are
      excluded for mass differences from the lightest neutralino up to 300 GeV.

PMID- 23005088
TI  - Flow-induced agitations create a granular fluid: effective viscosity and
      fluctuations.
AB  - We fluidize a granular medium with localized stirring in a split-bottom shear
      cell. We probe the mechanical response of quiescent regions far from the main
      flow by observing the vertical motion of cylindrical probes rising, sinking, and
      floating in the grains. First, we find that the probe motion suggests that the
      granular material behaves in a liquid-like manner: high-density probes sink and
      low-density probes float at the depth given by Archimedes' law. Second, we
      observe that the drag force on moving probes scales linearly with their velocity,
      which allows us to define an effective viscosity for the system. This effective
      viscosity is inversely proportional to the rotation rate of the disk which drives
      the split bottom flow. Moreover, the apparent viscosity depends on radius and
      mass of the probe: despite the linear dependence of the drag forces on sinking
      speed of the probe, the granular medium is not simply Newtonian, but exhibits a
      more complex rheology. The decrease of viscosity with filling height of the cell,
      combined with the poor correlation between local strain rate and viscosity,
      suggests that the fluid-like character of the material is set by agitations
      generated in the stirred region: the relation between applied stress and observed
      strain rate in one location depends on the strain rate in another location. We
      probe the nature of the granular fluctuations that we believe mediates these
      nonlocal interactions by characterizing the small and random up and down motion
      that the probe experiences. These Gaussian fluctuations exhibit a mix of
      diffusive and subdiffusive behavior at short times and saturate at a value of
      roughly 1/10th of a grain diameter longer times, consistent with the picture of a
      random walker in a potential well. The product of crossover time and effective
      viscosity is constant, evidencing a direct link between fluctuations and
      viscosity.

PMID- 23005089
TI  - Fluctuation-dissipation relations for motions of center of mass in driven
      granular fluids under gravity.
AB  - We investigated the validity of fluctuation-dissipation relations in the
      nonequilibrium stationary state of fluidized granular media under gravity by two
      independent approaches, based on theory and numerical simulations. A
      phenomenological Langevin-type theory describing the fluctuation of center of
      mass height, which was originally constructed for a one-dimensional granular gas
      on a vibrating bottom plate, was generalized to any dimensionality, even for the
      case in which the vibrating bottom plate is replaced by a thermal wall. The
      theory predicts a fluctuation-dissipation relation known to be satisfied at
      equilibrium, with a modification that replaces the equilibrium temperature by an
      effective temperature defined by the center of mass kinetic energy. To test the
      validity of the fluctuation-dissipation relation, we performed extensive and
      accurate event-driven molecular dynamics simulations for the model system with a
      thermal wall at the bottom. The power spectrum and response function of the
      center of mass height were measured and closely compared with theoretical
      predictions. It is shown that the fluctuation-dissipation relation for the
      granular system is satisfied, especially in the high-frequency (short time)
      region, for a wide range of system parameters. Finally, we describe the
      relationship between systematic deviations in the low-frequency (long time)
      region and the time scales of the driven granular system.

PMID- 23004963
TI  - Search for pair production of a heavy up-type quark decaying to a W boson and a b
      quark in the lepton + jets channel with the ATLAS detector.
AB  - A search is presented for production of a heavy up-type quark (t') together with
      its antiparticle, assuming subsequent decay to a W boson and a b quark, t't[over 
      ]'->W(+)bW(-)b[over -]. The search is based on 1.04 fb(-1) of proton-proton
      collisions at ?[s]=7 TeV collected by the ATLAS detector at the CERN Large Hadron
      Collider. Data are analyzed in the lepton+jets final state, characterized by a
      high transverse momentum isolated electron or muon, high missing transverse
      momentum, and at least three jets. No significant excess of events above the
      background expectation is observed. A 95% C.L. lower limit of 404 GeV is set for
      the mass of the t' quark.

PMID- 23005091
TI  - Hydrodynamically induced rhythmic motion of optically driven colloidal particles
      on a ring.
AB  - We experimentally study the motion of optically driven colloidal particles on a
      circular path by varying their number N. Although an identical driving force is
      applied to each particle, their equally spaced configuration is hydrodynamically
      unstable, and a doublet configuration is spontaneously formed. In small-N
      systems, the angular difference between neighboring particles exhibits
      oscillatory or nonoscillatory behavior. The number of oscillatory modes that
      appear depends on the maximum number of doublets that the system can contain.
      Frequent switching between different modes was observed with increasing N. The
      characteristic frequencies of the oscillatory modes are discussed theoretically
      by linear stability analysis of the equations that govern the motion of
      hydrodynamically coupled particles. The evaluated frequencies of the slowest
      modes exhibit reasonably good agreement with those of the mainly observed modes
      in experiments. The relationship between the characteristic frequencies and
      specific configurations is confirmed experimentally by setting a specific initial
      configuration for the particles. An increase in N also enhances the mean angular
      velocity of the particles owing to the reduced effective viscosity in large-N
      systems.

PMID- 23005095
TI  - Langevin dynamics simulations of a two-dimensional colloidal crystal under
      confinement and shear.
AB  - Langevin dynamics simulations are used to study the effect of shear on a two
      dimensional colloidal crystal (with implicit solvent) confined by structured
      parallel walls. When walls are sheared very slowly, only two or three crystalline
      layers next to the walls move along with them, while the inner layers of the
      crystal are only slightly tilted. At higher shear velocities, this inner part of
      the crystal breaks into several pieces with different orientations. The velocity
      profile across the slit is reminiscent of shear banding in flowing soft
      materials, where liquid and solid regions coexist; the difference, however, is
      that in the latter case the solid regions are glassy while here they are
      crystalline. At even higher shear velocities, the effect of the shearing becomes
      smaller again. Also the effective temperature near the walls (deduced from the
      velocity distributions of the particles) decreases again when the wall velocity
      gets very large. When the walls are placed closer together, thereby introducing
      an incommensurability between the periodicity of the confined crystal and the
      walls, a structure containing a soliton staircase arises in simulations without
      shear. Introducing shear increases the disorder in these systems until no
      solitons are visible anymore. Instead, similar structures like in the case
      without mismatch result. At high shear rates, configurations where the
      incommensurability of the crystalline structure is compensated by the creation of
      holes become relevant.

PMID- 23005094
TI  - Random versus sequential pathway of molecular self-assembly.
AB  - Two important assumptions are often made in the analysis of molecular self
      assembly at equilibrium, viz., that sequential is preferred to random aggregation
      and that the equilibrium constants at each stage of aggregation are equal, though
      both assumptions have not been justified strictly. In the present work we show
      that molecular self-assembly leading to formation of linear polymers and
      proceeding in a random manner appears to be less entropically favored than
      sequential aggregation, which provides a physical background for assuming
      sequential aggregation when studying molecular self-assembly in solution. Exact
      equations for analysis of experimental data for molecular assembly proceeding in
      a sequential manner were derived by taking strict account of the profile of the
      equilibrium constant, which provides a physically more correct approach than that
      using the conventional indefinite equilibrium constant (EK) model.

PMID- 23005097
TI  - Modeling the structure of liquids and crystals using one- and two-component
      modified phase-field crystal models.
AB  - A modified phase-field crystal model in which the free energy may be minimized by
      an order parameter profile having isolated bumps is investigated. The phase
      diagram is calculated in one and two dimensions and we locate the regions where
      modulated and uniform phases are formed and also regions where localized states
      are formed. We investigate the effectiveness of the phase-field crystal model for
      describing fluids and crystals with defects. We further consider a two-component
      model and elucidate how the structure transforms from hexagonal crystalline
      ordering to square ordering as the concentration changes. Our conclusion contains
      a discussion of possible interpretations of the order parameter field.

PMID- 23005092
TI  - Packings of monodisperse emulsions in flat microfluidic channels.
AB  - In the lateral confinement of a flat microfluidic channel, monodisperse emulsion
      droplets spontaneously self-organize in a variety of topologically different
      packings. The explicit construction of mechanically equilibrated arrangements of
      effectively two-dimensional congruent droplet shapes reveals the existence of
      multiple mechanical equilibria depending on channel width W, droplet area A{d},
      and volume fraction phi of the dispersed phase. The corresponding boundaries of
      local or global stability are summarized in a packing diagram for congruent
      droplet shapes in terms of the dimensionless channel width w=W/sqrt[A_{d}] and
      phi. In agreement with experimental results, an increasingly strong hysteresis of
      the transition between single-row and two-row packings is observed during changes
      of w above a threshold volume fraction of phi?0.813.

PMID- 23005090
TI  - Deformation of Platonic foam cells: effect on growth rate.
AB  - The diffusive growth rate of a polyhedral cell in dry three-dimensional foams
      depends on details of shape beyond cell topology, in contrast to the situation in
      two dimensions, where, by von Neumann's law, the growth rate depends only on the
      number of cell edges. We analyze the dependence of the instantaneous growth rate
      on the shape of single foam cells surrounded by uniform pressure; this is
      accomplished by supporting the cell with films connected to a wire frame and
      inducing cell distortions by deforming the wire frame. We consider three foam
      cells with a very simple topology; these are the Platonic foam cells, which
      satisfy Plateau's laws and are based on the trivalent Platonic solids
      (tetrahedron, cube, and dodecahedron). The Surface Evolver is used to model cell
      deformations induced through extension, compression, shear, and torsion of the
      wire frames. The growth rate depends on the deformation mode and frame size and
      can increase or decrease with increasing cell distortion. The cells have negative
      growth rates, in general, but dodecahedral cells subjected to torsion in small
      wire frames can have positive growth rates. The deformation of cubic cells is
      demonstrated experimentally.

PMID- 23005093
TI  - Structure of colloidosomes with tunable particle density: simulation versus
      experiment.
AB  - Colloidosomes are created in the laboratory from a Pickering emulsion of water
      droplets in oil. The colloidosomes have approximately the same diameter and by
      choosing (hairy) particles of different diameters it is possible to control the
      particle density on the droplets. The experiment is performed at room
      temperature. The radial distribution function of the assembly of (primary)
      particles on the water droplet is measured in the laboratory and in a computer
      experiment of a fluid model of particles with pairwise interactions on the
      surface of a sphere.

PMID- 23005096
TI  - Connectivity percolation in suspensions of hard platelets.
AB  - We present a study on connectivity percolation in suspensions of hard platelets
      by means of Monte Carlo simulation. We interpret our results using a contact
      volume argument based on an effective single-particle cell model. It is commonly
      assumed that the percolation threshold of anisotropic objects scales as their
      inverse aspect ratio. While this rule has been shown to hold for rodlike
      particles, we find that for hard platelike particles the percolation threshold is
      nonmonotonic in the aspect ratio. It exhibits a shallow minimum at intermediate
      aspect ratios and then saturates to a constant value. This effect is caused by
      the isotropic-nematic transition preempting the percolation transition. Hence the
      common strategy to use highly anisotropic, conductive particles as fillers in
      composite materials in order to produce conduction at low filler concentration is
      expected to fail for platelike fillers such as graphene and graphite
      nanoplatelets.

PMID- 23005098
TI  - Relaxation mechanisms in glassy dynamics: the Arrhenius and fragile regimes.
AB  - Generic glass formers exhibit at least two characteristic changes in their
      relaxation behavior, first to an Arrhenius-type relaxation at some characteristic
      temperature and then at a lower characteristic temperature to a super-Arrhenius
      (fragile) behavior. We address these transitions by studying the statistics of
      free energy barriers for different systems at different temperatures and space
      dimensions. We present a clear evidence for changes in the dynamical behavior at
      the transition to Arrhenius and then to a super-Arrhenius behavior. A simple
      model is presented, based on the idea of competition between single-particle and
      cooperative dynamics. We argue that Arrhenius behavior can take place as long as
      there is enough free volume for the completion of a simple T1 relaxation process.
      Once free volume is absent one needs a cooperative mechanism to "collect" enough
      free volume. We show that this model captures all the qualitative behavior
      observed in simulations throughout the considered temperature range.

PMID- 23005101
TI  - Space-time correlated two-particle hopping in glassy fluids: structural
      relaxation, irreversibility, decoupling, and facilitation.
AB  - The microscopic nonlinear Langevin equation (NLE) theory of correlated two
      particle dynamics in dense fluids of spherical particles is extended to construct
      a predictive model of multiple correlated hopping and recaging events of a pair
      of tagged particles as a function of their initial separation. Modest coarse
      graining over the liquid structural disorder allows contact to be made with
      various definitions of irreversible particle motion within the context of a
      multistate Markov model. The correlated space-time hopping process that underlies
      structural relaxation can also be analyzed in the context of kinetically
      constrained models. The dependence of microscopically defined mean persistence
      and exchange times, their distributions, and relaxation-diffusion decoupling on
      hard-sphere fluid volume fraction is derived from a model in which irreversible
      jumps serve as the nucleating persistence event. For a subset of questions, the
      predictions of the two-particle theory are compared with results from the earlier
      single-particle NLE approach.

PMID- 23005102
TI  - Simple solvable energy-landscape model that shows a thermodynamic phase
      transition and a glass transition.
AB  - When a liquid melt is cooled, a glass or phase transition can be obtained
      depending on the cooling rate. Yet, this behavior has not been clearly captured
      in energy-landscape models. Here, a model is provided in which two key
      ingredients are considered in the landscape, metastable states and their
      multiplicity. Metastable states are considered as in two level system models.
      However, their multiplicity and topology allows a phase transition in the
      thermodynamic limit for slow cooling, while a transition to the glass is obtained
      for fast cooling. By solving the corresponding master equation, the minimal speed
      of cooling required to produce the glass is obtained as a function of the
      distribution of metastable states.

PMID- 23005099
TI  - Manifestations of dynamical facilitation in glassy materials.
AB  - By characterizing the dynamics of idealized lattice models with a tunable kinetic
      constraint, we explore the different ways in which dynamical facilitation
      manifests itself within the local dynamics of glassy materials. Dynamical
      facilitation is characterized both by a mobility transfer function, the
      propensity for highly mobile regions to arise near regions that were previously
      mobile, and by a facilitation volume, the effect of an initial dynamical event on
      subsequent dynamics within a region surrounding it. Sustained bursts of dynamical
      activity-avalanches-are shown to occur in kinetically constrained models, but,
      contrary to recent claims, we find that the decreasing spatiotemporal extent of
      avalanches with increased supercooling previously observed in granular
      experiments does not imply diminishing facilitation. Viewed within the context of
      existing simulation and experimental evidence, our findings show that dynamical
      facilitation plays a significant role in the dynamics of systems investigated
      over the range of state points accessible to molecular simulations and granular
      experiments.

PMID- 23005103
TI  - Wetting transition in the two-dimensional Blume-Capel model: a Monte Carlo study.
AB  - The wetting transition of the Blume-Capel model is studied by a finite-size
      scaling analysis of L*M lattices where competing boundary fields +/-H_{1} act on
      the first or last row of the L rows in the strip, respectively. We show that
      using the appropriate anisotropic version of finite-size scaling, critical
      wetting in d=2 is equivalent to a "bulk" critical phenomenon with exponents
      alpha=-1, beta=0, and gamma=3. These concepts are also verified for the Ising
      model. For the Blume-Capel model, it is found that the field strength H_{1c}(T)
      where critical wetting occurs goes to zero when the bulk second-order transition
      is approached, while H_{1c}(T) stays nonzero in the region where in the bulk a
      first-order transition from the ordered phase, with nonzero spontaneous
      magnetization, to the disordered phase occurs. Interfaces between coexisting
      phases then show interfacial enrichment of a layer of the disordered phase which
      exhibits in the second-order case a finite thickness only. A tentative discussion
      of the scaling behavior of the wetting phase diagram near the tricritical point
      is also given.

PMID- 23005100
TI  - Analytical model for three-dimensional Mercedes-Benz water molecules.
AB  - We developed a statistical model which describes the thermal and volumetric
      properties of water-like molecules. A molecule is presented as a three
      dimensional sphere with four hydrogen-bonding arms. Each water molecule interacts
      with its neighboring waters through a van der Waals interaction and an
      orientation-dependent hydrogen-bonding interaction. This model, which is largely
      analytical, is a variant of a model developed before for a two-dimensional
      Mercedes-Benz model of water. We explored properties such as molar volume,
      density, heat capacity, thermal expansion coefficient, and isothermal
      compressibility as a function of temperature and pressure. We found that the
      volumetric and thermal properties follow the same trends with temperature as in
      real water and are in good general agreement with Monte Carlo simulations,
      including the density anomaly, the minimum in the isothermal compressibility, and
      the decreased number of hydrogen bonds upon increasing the temperature.

PMID- 23005104
TI  - Multiscale deformation of a liquid surface in interaction with a nanoprobe.
AB  - The interaction between a nanoprobe and a liquid surface is studied. The surface
      deformation depends on physical and geometric parameters, which are depicted by
      employing three dimensionless parameters: Bond number B_{o}, modified Hamaker
      number H_{a}, and dimensionless separation distance D. The evolution of the
      deformation is described by a strongly nonlinear partial differential equation,
      which is solved by means of numerical methods. The dynamic analysis of the liquid
      profile points out the existence of a critical distance D_{min}, below which the
      irreversible wetting process of the nanoprobe happens. For D >= D_{min}, the
      numerical results show the existence of two deformation profiles, one stable and
      another unstable from the energetic point of view. Different deformation length
      scales, characterizing the stable liquid equilibrium interface, define the near-
      and the far-field deformation zones, where self-similar profiles are found.
      Finally, our results allow us to provide simple relationships between the
      parameters, which leads to determine the optimal conditions when performing
      atomic force microscope measurements over liquids.

PMID- 23005105
TI  - Thermal singularity and droplet motion in one-component fluids on solid
      substrates with thermal gradients.
AB  - Using a continuum model capable of describing the one-component liquid-gas
      hydrodynamics down to the contact line scale, we carry out numerical simulation
      and physical analysis for the droplet motion driven by thermal singularity. For
      liquid droplets in one-component fluids on heated or cooled substrates, the
      liquid-gas interface is nearly isothermal. Consequently, a thermal singularity
      occurs at the contact line and the Marangoni effect due to temperature gradient
      is suppressed. Through evaporation or condensation in the vicinity of the contact
      line, the thermal singularity makes the contact angle increase with the
      increasing substrate temperature. This effect on the contact angle can be used to
      move the droplets on substrates with thermal gradients. Our numerical results for
      this kind of droplet motion are explained by a simple fluid dynamical model at
      the droplet length scale. Since the mechanism for droplet motion is based on the
      change of contact angle, a separation of length scales is exhibited through a
      comparison between the droplet motion induced by a wettability gradient and that
      by a thermal gradient. It is shown that the flow field at the droplet length
      scale is independent of the statics or dynamics at the contact line scale.

PMID- 23005106
TI  - Evaporation of picoliter droplets on surfaces with a range of wettabilities and
      thermal conductivities.
AB  - The evaporation of picoliter water and ethanol droplets generated by drop-on
      demand inkjet printing was investigated on substrates with apparent contact
      angles between 10^{?} and 135^{?} and thermal conductivities between 0.25 and 149
      Wm^{-1}K^{-1}. Drying times were calculated from a diffusion-limited model for
      droplets with both pinned and moving contact lines as a function of droplet
      diameter and apparent contact angle. Droplets with a moving contact line take
      longer to dry on hydrophilic substrates than pinned droplets. The difference in
      drying times between evaporative modes vanishes at large apparent contact angles.
      Hence similar drying times are obtained for both modes on hydrophobic substrates.
      The predicted drying times for glass and silicon substrates were in good
      quantitative agreement with experimental data, suggesting that thermal effects
      are negligible for substrates of these base materials. However, on a PTFE
      substrate which has a lower thermal conductivity more relevant to inkjet
      printing, evaporative cooling reduces the evaporation rate causing drying times
      to be underpredicted by isothermal models.

PMID- 23005107
TI  - Coarsening of elastically stressed, strongly anisotropic driven thin films.
AB  - A diffuse interface model is developed to investigate the growth and coarsening
      in driven thin films under the influence of strong surface energy anisotropy,
      misfit strain, mass deposition, and diffusion. Two high-order regularizations are
      used to remove the ill-posedness introduced by the strong anisotropy: a Willmore
      (or bending energy) regularization and a simplified linear regularization. For
      similar effective growth rates and regularization strengths, the two
      regularizations undergo similar dynamics and coarsening, as peaks (antikinks) and
      valleys (kinks) of the corrugated surface are removed as the film grows.
      Competition among the influence of elastic strains, surface energy anisotropy and
      the rate of deposition lead to a change in the coarsening events compared to that
      observed in unstressed thin films. As the rate of deposition is increased, the
      primary coarsening events change from a combination of both antikink-ternary and
      binary events at low deposition rates, to binary events at moderate rates, and
      finally to kink-ternary events at high rates. The kink-ternary events are the
      only coarsening events observed in growing unstressed films at all deposition
      rates. Accordingly, the coarsening dynamics of two-dimensional (2D) stressed
      films is much faster than for unstressed films at low deposition rates. In
      addition, deep grooves may form in the film due to the Asaro-Tiller-Grinfeld
      instability and may lead to the breakup of the film into islands. At higher
      deposition rates, the evolution of stressed films is found to become limited by
      the surface energy anisotropy and the regularizations, which inhibits groove
      formation. The corresponding coarsening events and rates then tend toward those
      observed in unstressed films. Preliminary results of 3D thin films indicate that
      coarsening processes in elastically stressed films are also much faster than
      their unstressed counterparts at low deposition rates. In three dimensions,
      however, the coarsening events are also found to involve saddles.

PMID- 23005108
TI  - Surface free energies for nematic shells.
AB  - We propose a continuum model to describe the molecular alignment in thin nematic
      shells. By contrast with previous accounts, the two-dimensional free energy,
      aimed at describing the physics of thin films of nematics deposited on curved
      substrates, is not postulated, but it is deduced from the conventional three
      dimensional theories of nematic liquid crystals. Both the director and the order
      tensor theories are taken into account. The so-obtained surface energies exhibit
      extra terms compared to earlier models. These terms reflect the coupling of the
      shell extrinsic curvature with the nematic order parameters. As expected, the
      shape of the shell plays a key role in the equilibrium configurations of nematics
      coating it.

PMID- 23005109
TI  - Multistability in planar liquid crystal wells.
AB  - A planar bistable liquid crystal device, reported in Tsakonas et al. [Appl. Phys.
      Lett. 90, 111913 (2007)], is modeled within the Landau-de Gennes theory for
      nematic liquid crystals. This planar device consists of an array of square
      micrometer-sized wells. We obtain six different classes of equilibrium profiles
      and these profiles are classified as diagonal or rotated solutions. In the strong
      anchoring case, we propose a Dirichlet boundary condition that mimics the
      experimentally imposed tangent boundary conditions. In the weak anchoring case,
      we present a suitable surface energy and study the multiplicity of solutions as a
      function of the anchoring strength. We find that diagonal solutions exist for all
      values of the anchoring strength W >= 0, while rotated solutions only exist for W
      >= W_{c}>0, where W_{c} is a critical anchoring strength that has been computed
      numerically. We propose a dynamic model for the switching mechanisms based on
      only dielectric effects. For sufficiently strong external electric fields, we
      numerically demonstrate diagonal-to-rotated and rotated-to-diagonal switching by
      allowing for variable anchoring strength across the domain boundary.

PMID- 23005110
TI  - Orientational order parameters of a de Vries-type ferroelectric liquid crystal
      obtained by polarized Raman spectroscopy and x-ray diffraction.
AB  - The orientational order parameters (P{2}) and (P{4}) of the ferroelectric, de
      Vries-type liquid crystal 9HL have been determined in the SmA and SmC phases by
      means of polarized Raman spectroscopy, and in the SmA phase using x-ray
      diffraction. Quantum density functional theory predicts Raman spectra for 9HL
      that are in good agreement with the observations and indicates that the strong
      Raman band probed in the experiment corresponds to the uniaxial, coupled
      vibration of the three phenyl rings along the molecular long axis. The magnitudes
      of the orientational order parameters obtained in the Raman and x-ray experiments
      differ dramatically from each other, a discrepancy that is resolved by
      considering that the two techniques probe the orientational distributions of
      different molecular axes. We have developed a systematic procedure in which we
      calculate the angle between these axes and rescale the orientational order
      parameters obtained from x-ray scattering with results that are then in good
      agreement with the Raman data. At least in the case of 9HL, the results obtained
      by both techniques support a "sugar loaf" orientational distribution in the SmA
      phase with no qualitative difference to conventional smectics A. The role of
      individual molecular fragments in promoting de Vries-type behavior is considered.

PMID- 23005112
TI  - Surface and bulk contributions to nematic order reconstruction.
AB  - Nematic molecules confined in an asymmetric pi cell and subjected to strong
      electric fields exhibit textural distortions involving nematic order variations,
      described by the Landau-de Gennes Q-tensor theory. We investigated the evolution
      of order variations as function of the applied electric pulse amplitude and of
      the nematic surface pretilt anchoring angles by implementing a Q-tensor model
      with a moving mesh finite element method. The proposed technique is able to
      clearly distinguish the bulk and the surface order reconstruction which occur in
      the cell.

PMID- 23005111
TI  - Dielectric technique to measure the twist elastic constant of liquid crystals:
      the case of a bent-core material.
AB  - The effect of director pretilt on the twist magnetic Freedericksz transition of
      nematics was investigated in a planar cell. The director configuration was
      calculated as a function of magnetic inductance. The dielectric and optical
      response of the nematic liquid crystal was numerically modeled. A dielectric
      measurement method for determining the elastic constant K_{22} is presented. The
      influence of the conditions for the Mauguin effect is discussed. The theoretical
      predictions were confirmed by our experiments. Experimental data for all elastic
      constants of a bent-core nematic material are presented and discussed.

PMID- 23005113
TI  - Isotropic and nematic phases of the hard spheroid fluid: a virial approach.
AB  - We use a high level virial expansion to investigate the properties of the
      isotropic and nematic phases of the hard spheroid fluid. We use the Monte Carlo
      techniques described previously to calculate the virial coefficients up to
      seventh order and we represent the dependence of these coefficients on particle
      orientations via a spherical harmonic expansion. The expansion coefficients are
      determined using Lebedev quadrature which carries out the angular integration
      required exactly. For fairly spherical spheroids (1/3<a/b<3, where a and b are
      the semiaxes of the spheroid) the virial expansion appears to be convergent in
      both the isotropic and nematic phases up to high density. For more aspherical
      particles, the predictions varied in a more erratic fashion upon increasing the
      number of virials. The use of a finite angular basis set to represent the
      orientationally dependent virial coefficients could be a contributory cause to
      this.

PMID- 23005114
TI  - Structural origin of enhanced translational diffusion in two-dimensional hard
      ellipse fluids.
AB  - The static correlations and diffusive dynamics of hard ellipses are investigated
      in the isotropic and nematic phases by Monte Carlo simulation. In particular, an
      enhancement of the translational diffusion with respect to the rotational
      diffusion is observed at an onset concentration phi_{on} within the isotropic
      phase, which is explained in terms of the formation of unstable nematic-like
      regions with a mean lifetime that exceeds the characteristic time of diffusion at
      phi_{on}. The relevance to the onset of spatially heterogeneous dynamics in
      supercooled glass-forming liquids is discussed.

PMID- 23005115
TI  - Aspect ratio and polydispersity dependence of isotropic-nematic transition in
      discotic suspensions.
AB  - We demonstrate the strong dependency of the isotropic-nematic (I-N) transition of
      discotic suspensions on the aspect ratio (xi = thickness/diameter) via control of
      the sizes of pristine ZrP crystals and subsequent exfoliation to monolayers. The
      size fractionation of the I-N transition facilitates the analysis of the effect
      of polydispersity. A systematic variation in the aspect ratio in the low aspect
      ratio region (0.001 < xi < 0.01) showed that the I-N transition volume fraction
      increases with the aspect ratio in agreement with computer simulations. It was
      found that the transition volume fractions scale with aspect ratio phi_{I,N} =
      mxi^{1.36+/-0.07}, where the prefactor m strongly depends on size polydispersity
      for phi_{N} but does not depend on size polydispersity for phi_{I} with phi_{I}
      and phi_{N} being the volume fractions of the isotropic and the nematic phases on
      the cloud curves, respectively.

PMID- 23005116
TI  - Enhanced Landau-de Gennes potential for nematic liquid crystals from a systematic
      coarse-graining procedure.
AB  - The macroscopic theory of nematics is conveniently described in terms of the
      phenomenological Landau-de Gennes free energy. Here we show how such an effective
      free energy can be obtained explicitly from a microscopic model via the help of a
      systematic coarse-graining procedure. We test our approach for the two- and three
      dimensional Lebwohl-Lasher model of nematics. The effective free energy that we
      obtain is consistent with the phenomenological Landau-de Gennes form for weak
      orientational ordering and the Maier-Saupe theory of the isotropic-nematic
      transition. For strong orientational ordering, however, the effective free energy
      increases rapidly and diverges logarithmically near the fully oriented state. The
      explicit form for the regularized Landau-de Gennes potential proposed here
      restricts the order parameter to physical admissible values and reproduces our
      numerical data accurately.

PMID- 23005117
TI  - Solution of the Onsager model for the structure of rigid rods confined on a
      spherical surface.
AB  - We consider a free energy, within the framework of the Onsager approximation, for
      a spatially and orientationally inhomogeneous distribution of hard rods confined
      on a spherical surface. These rods interact with each other though the excluded
      volume interaction, forming a textured nematic structure on the spherical surface
      at high surface coverage. Our numerical solution to the model shows that the
      splay state, where on average rods line up in parallel to the longitudes on the
      spherical surface, is the only stable state. Other types of textures that have
      recently been suggested were also tested and all yield higher free energy than
      that of a ground splay state. We also provide a study of the disorder-splay
      transition, which is shown to have first-order characteristics.

PMID- 23005118
TI  - Separation of long linear polymers in gel electrophoresis with alternating
      electric fields: a theoretical study using the necklace model.
AB  - The necklace model, which mimics the reptation of a chain of N beads in a square
      lattice, is used to study the drift velocity of charged linear polymers in gels
      under an applied electric field that periodically changes its direction. The
      characteristics of the model allow us to determine the effects of the alternating
      electric field on the chains' dynamics. We explain why chains of different N can
      be made to move in opposite directions with a nonuniform electric field with
      certain values of intensity and frequency. The key point is that, when
      alternating electric fields are applied, longer chains spend more time out of the
      steady-state regime than lower chains. Numerical results are obtained by means of
      Monte Carlo simulations and they are qualitatively in agreement with experiments
      of DNA migration in gel electrophoresis.

PMID- 23005119
TI  - Asymmetry-symmetry transition of double-sided adhesive tapes.
AB  - We report on the debonding process of a double-sided adhesive tape sandwiched
      between two glass plates. When the glass plates are separated from each other at
      a constant rate, a highly asymmetric extension of top and bottom adhesive layers
      and bending of the inner film are observed first. As the separation proceeds, the
      elongation of both layers becomes symmetric, and the inner film becomes flat
      again. When this happens, there appears a local maximum in the force-displacement
      curve. We explain this asymmetry-symmetry transition and discuss the role of the
      bimodal force-displacement relation of each adhesive layer. We also discuss the
      effect of the inner film thickness and the separation rate on the debonding
      behavior, which causes undesirable early detachment of the double-sided adhesive
      tape in a certain condition.

PMID- 23005120
TI  - Process time distribution of driven polymer transport.
AB  - We discuss the temporal distribution of dynamic processes in driven polymer
      transport inherent to flexible chains due to stochastic tension propagation. The
      stochasticity originates from the disordered initial configuration of an
      equilibrium polymer coil, which results in random paths for tension propagation.
      We consider the process time for when translocation occurs across a fixed pore
      and when stretching occurs by pulling the chain end. A scaling argument for the
      mean and standard deviation of the process time is provided using the two-phase
      picture for stochastic propagation. The two cases are found to differ remarkably.
      The process time distribution of the translocation exhibits substantial spreading
      even in the long-chain limit, unlike that found for the dynamics of polymer
      stretching. In addition, the process time distribution in the driven
      translocation is shown to have a characteristic asymmetric shape.

PMID- 23005121
TI  - Applying the Kelvin probe to biological tissues: theoretical and computational
      analyses.
AB  - The Kelvin probe measures surface electrical potential without making physical
      contact with the specimen. It relies on capacitive coupling between an
      oscillating metal tip that is normal to a specimen's surface. Kelvin probes have
      been increasingly used to study surface and electrical properties of metals and
      semiconductors and are capable of detecting material surface potentials with
      submillivolt resolution at a micrometer spatial scale. Its capability for
      measuring electrical potential without being confounded by electrode-specimen
      contact makes extending its use towards biological materials particularly
      appealing. However, the theoretical basis for applying the Kelvin probe to
      dielectric or partially conductive materials such as biological tissue has not
      been evaluated and remains unclear. This study develops the theoretical basis
      underlying Kelvin probe measurements in five theoretical materials: highly
      conductive, conductive dielectric with rapid charge relaxation, conductive
      dielectric with slow charge relaxation, perfect dielectric, and tissue with a
      bulk serial resistance. These theoretically derived equations are then
      computationally analyzed using parameters from both theoretical specimens and
      actual biomaterials-including wet skin, dry skin, cerebrospinal fluid, and
      tendon. Based on these analyses, a Kelvin probe performs in two distinct ways
      depending on the charge relaxation rates of the sample: The specimen is treated
      either as a perfect dielectric or as highly conductive material. Because of their
      rapid relaxation rate and increased permittivity biomaterials behave similarly to
      highly conductive materials, such as metal, when evaluated by the Kelvin probe.
      These results indicate that the Kelvin probe can be readily applied to studying
      the surface potential of biological tissue.

PMID- 23005122
TI  - Using noise to determine cardiac restitution with memory.
AB  - Variation in cardiac pacing cycles, as seen, for example, in heart rate
      variability, has been observed for decades. Contemporarily, various mathematical
      models have been constructed to investigate the electrical activity of paced
      cardiac cells. Yet there has not been a study of these cardiac models when there
      is variation in the pacing cycles such as noise. We present a method that uses
      the stochasticity of pacing cycles to determine approximate models of the
      dynamics of cardiac cells, and use these models to detect bifurcations to
      alternans.

PMID- 23005123
TI  - Dynamical self-regulation in self-propelled particle flows.
AB  - We study a continuum model of overdamped self-propelled particles with aligning
      interactions in two dimensions. Combining analytical theory and computations, we
      map out the phase diagram for the parameter space covered by the model. We find
      that the system self-organizes into two robust structures in different regions of
      parameter space: solitary waves composed of ordered swarms moving through a low
      density disordered background, and stationary radially symmetric asters. The self
      regulating nature of the flow yields phase separation, ubiquitous in this class
      of systems, and controls the formation of solitary waves. Self-propulsion and the
      associated active convection play a crucial role in aster formation.

PMID- 23005124
TI  - Effects of cooperative ion-channel interactions on the dynamics of excitable
      membranes.
AB  - Cooperative interactions between ion channels are known to exist, but have so far
      received relatively little attention in the study of excitable membranes. Based
      on bifurcation analysis and stochastic simulations of an extended Morris-Lecar
      model, we show that cooperativity and anticooperativity can modify the range of
      sustained firing and cell-intrinsic noise, induce multistability, and account for
      a number of experimental observations, including prolongation of action-potential
      duration. We hypothesize that channel interactions could be an efficient
      mechanism to regulate the activity of neurons or cardiac muscle cells.

PMID- 23005125
TI  - Complex synchronous behavior in interneuronal networks with delayed inhibitory
      and fast electrical synapses.
AB  - Networks of fast-spiking interneurons are crucial for the generation of neural
      oscillations in the brain. Here we study the synchronous behavior of
      interneuronal networks that are coupled by delayed inhibitory and fast electrical
      synapses. We find that both coupling modes play a crucial role by the
      synchronization of the network. In addition, delayed inhibitory synapses affect
      the emerging oscillatory patterns. By increasing the inhibitory synaptic delay,
      we observe a transition from regular to mixed oscillatory patterns at a critical
      value. We also examine how the unreliability of inhibitory synapses influences
      the emergence of synchronization and the oscillatory patterns. We find that low
      levels of reliability tend to destroy synchronization and, moreover, that
      interneuronal networks with long inhibitory synaptic delays require a minimal
      level of reliability for the mixed oscillatory pattern to be maintained.

PMID- 23005126
TI  - Controlling activation site density by low-energy far-field stimulation in
      cardiac tissue.
AB  - Tachycardia and fibrillation are potentially fatal arrhythmias associated with
      the formation of rotating spiral waves in the heart. Presently, the termination
      of these types of arrhythmia is achieved by use of antitachycardia pacing or
      cardioversion. However, these techniques have serious drawbacks, in that they
      either have limited application or produce undesirable side effects. Low-energy
      far-field stimulation has recently been proposed as a superior therapy. This
      proposed therapeutic method would exploit the phenomenon in which the application
      of low-energy far-field shocks induces a large number of activation sites
      ("virtual electrodes") in tissue. It has been found that the formation of such
      sites can lead to the termination of undesired states in the heart and the
      restoration of normal beating. In this study we investigate a particular aspect
      of this method. Here we seek to determine how the activation site density depends
      on the applied electric field through in vitro experiments carried out on
      neonatal rat cardiac tissue cultures. The results indicate that the activation
      site density increases exponentially as a function of the intracellular
      conductivity and the level of cell isotropy. Additionally, we report numerical
      results obtained from bidomain simulations of the Beeler-Reuter model that are
      quantitatively consistent with our experimental results. Also, we derive an
      intuitive analytical framework that describes the activation site density and
      provides useful information for determining the ratio of longitudinal to
      transverse conductivity in a cardiac tissue culture. The results obtained here
      should be useful in the development of an actual therapeutic method based on low
      energy far-field pacing. In addition, they provide a deeper understanding of the
      intrinsic properties of cardiac cells.

PMID- 23005127
TI  - Blinking fluorescence of single donor-acceptor pairs: important role of "dark''
      states in resonance energy transfer via singlet levels.
AB  - The influence of triplet levels on Forster resonance energy transfer via singlet
      levels in donor-acceptor (D-A) pairs is studied. Four types of D-A pair are
      considered: (i) two-level donor and two-level acceptor, (ii) three-level donor
      and two-level acceptor, (iii) two-level donor and three-level acceptor, and (iv)
      three-level donor and three-level acceptor. If singlet-triplet transitions in a
      three-level acceptor molecule are ineffective, the energy transfer efficiency
      E=I_{A}/(I_{A}+I_{D}), where I_{D} and I_{A} are the average intensities of donor
      and acceptor fluorescence, can be described by the simple theoretical equation
      E(F)=FT_{D}/(1+FT_{D}). Here F is the rate of energy transfer, and T_{D} is the
      donor fluorescence lifetime. In accordance with the last equation, 100% of the
      donor electronic energy can be transferred to an acceptor molecule at FT_{D}?1.
      However, if singlet-triplet transitions in a three-level acceptor molecule are
      effective, the energy transfer efficiency is described by another theoretical
      equation, E(F)=F[over -](F)T_{D}/[1+F[over -](F)T_{D}]. Here F[over -](F) is a
      function of F depending on singlet-triplet transitions in both donor and acceptor
      molecules. Expressions for the functions F[over -](F) are derived. In this case
      the energy transfer efficiency will be far from 100% even at FT_{D}?1. The
      character of the intensity fluctuations of donor and acceptor fluorescence
      indicates which of the two equations for E(F) should be used to find the value of
      the rate F. Therefore, random time instants of photon emission in both donor and
      acceptor fluorescence are calculated by the Monte Carlo method for all four types
      of D-A pair. Theoretical expressions for start-stop correlators (waiting time
      distributions) in donor and acceptor fluorescence are derived. The probabilities
      w_{N}^{D}(t) and w_{N}^{A}(t) of finding N photons of donor and acceptor
      fluorescence in the time interval t are calculated for various values of the
      energy transfer rate F and for all four types of D-A pair. Comparison of the
      calculated D and A fluorescence trajectories with those measured by Weiss and co
      workers proves the important role of triplet levels in energy transfer via
      singlet levels.

PMID- 23005128
TI  - Generalized index for spatial data sets as a measure of complete spatial
      randomness.
AB  - Spatial data sets, generated from a wide range of physical systems can be
      analyzed by counting the number of objects in a set of bins. Previous work has
      been limited to equal-sized bins, which are inappropriate for some domains (e.g.,
      circular). We consider a nonequal size bin configuration whereby overlapping or
      nonoverlapping bins cover the domain. A generalized index, defined in terms of a
      variance between bin counts, is developed to indicate whether or not a spatial
      data set, generated from exclusion or nonexclusion processes, is at the complete
      spatial randomness (CSR) state. Limiting values of the index are determined.
      Using examples, we investigate trends in the generalized index as a function of
      density and compare the results with those using equal size bins. The smallest
      bin size must be much larger than the mean size of the objects. We can determine
      whether a spatial data set is at the CSR state or not by comparing the values of
      a generalized index for different bin configurations-the values will be
      approximately the same if the data is at the CSR state, while the values will
      differ if the data set is not at the CSR state. In general, the generalized index
      is lower than the limiting value of the index, since objects do not have access
      to the entire region due to blocking by other objects. These methods are applied
      to two applications: (i) spatial data sets generated from a cellular automata
      model of cell aggregation in the enteric nervous system and (ii) a known plant
      data distribution.

PMID- 23005129
TI  - Protein loops, solitons, and side-chain visualization with applications to the
      left-handed helix region.
AB  - Folded proteins have a modular assembly. They are constructed from regular
      secondary structures like alpha helices and beta strands that are joined together
      by loops. Here we develop a visualization technique that is adapted to describe
      this modular structure. In complement to the widely employed Ramachandran plot
      that is based on toroidal geometry, our approach utilizes the geometry of a two
      sphere. Unlike the more conventional approaches that describe only a given
      peptide unit, ours is capable of describing the entire backbone environment
      including the neighboring peptide units. It maps the positions of each atom to
      the surface of the two-sphere exactly how these atoms are seen by an observer who
      is located at the position of the central C_{alpha} atom. At each level of side
      chain atoms we observe a strong correlation between the positioning of the atom
      and the underlying local secondary structure with very little if any variation
      between the different amino acids. As a concrete example we analyze the left
      handed helix region of nonglycyl amino acids. This region corresponds to an
      isolated and highly localized residue independent sector in the direction of the
      C_{beta} carbons on the two-sphere. We show that the residue independent
      localization extends to C_{gamma} and C_{delta} carbons and to side-chain oxygen
      and nitrogen atoms in the case of asparagine and aspartic acid. When we extend
      the analysis to the side-chain atoms of the neighboring residues, we observe that
      left-handed beta turns display a regular and largely amino acid independent
      structure that can extend to seven consecutive residues. This collective pattern
      is due to the presence of a backbone soliton. We show how one can use our
      visualization techniques to analyze and classify the different solitons in terms
      of selection rules that we describe in detail.

PMID- 23005130
TI  - Pulling or compressing a vesicle by force: solution to the bending energy model.
AB  - The shape transformation induced by pulling or compressing a vesicle along the
      symmetric axis is discussed in light of the numerical solution to the bending
      energy model with fixed enclosing volume and surface area. A complete phase
      diagram in terms of the external force and reduced vesicle volume is
      investigated. Some experimental observations are explained by the solution.

PMID- 23005131
TI  - Multistability in a neuron model with extracellular potassium dynamics.
AB  - Experiments show a primary role of extracellular potassium concentrations in
      neuronal hyperexcitability and in the generation of epileptiform bursting and
      depolarization blocks without synaptic mechanisms. We adopt a physiologically
      relevant hippocampal CA1 neuron model in a zero-calcium condition to better
      understand the function of extracellular potassium in neuronal seizurelike
      activities. The model neuron is surrounded by interstitial space in which
      potassium ions are able to accumulate. Potassium currents, Na{+}-K{+} pumps,
      glial buffering, and ion diffusion are regulatory mechanisms of extracellular
      potassium. We also consider a reduced model with a fixed potassium concentration.
      The bifurcation structure and spiking frequency of the two models are studied. We
      show that, besides hyperexcitability and bursting pattern modulation, the
      potassium dynamics can induce not only bistability but also tristability of
      different firing patterns. Our results reveal the emergence of the complex
      behavior of multistability due to the dynamical [K{+}]{o} modulation on neuronal
      activities.

PMID- 23005132
TI  - Main transition in the Pink membrane model: finite-size scaling and the influence
      of surface roughness.
AB  - We consider the main transition in single-component membranes using computer
      simulations of the Pink model [D. A. Pink et al., Biochemistry 19, 349 (1980)].
      We first show that the accepted parameters of the Pink model yield a main
      transition temperature that is systematically below experimental values. This
      resolves an issue that was first pointed out by Corvera and co-workers [Phys.
      Rev. E 47, 696 (1993)]. In order to yield the correct transition temperature, the
      strength of the van der Waals coupling in the Pink model must be increased; by
      using finite-size scaling, a set of optimal values is proposed. We also provide
      finite-size scaling evidence that the Pink model belongs to the universality
      class of the two-dimensional Ising model. This finding holds irrespective of the
      number of conformational states. Finally, we address the main transition in the
      presence of quenched disorder, which may arise in situations where the membrane
      is deposited on a rough support. In this case, we observe a stable multidomain
      structure of gel and fluid domains, and the absence of a sharp transition in the
      thermodynamic limit.

PMID- 23005133
TI  - Stochastic single-gene autoregulation.
AB  - A detailed stochastic model of single-gene autoregulation is established and its
      solutions are explored when mRNA dynamics is fast compared with protein dynamics
      and in the opposite regime. The model includes all the sources of randomness that
      are intrinsic to the autoregulation process and it considers both transcriptional
      and post-transcriptional regulation. The time-scale separation allows the
      derivation of analytic expressions for the equilibrium distributions of protein
      and mRNA. These distributions are generally well described in the continuous
      approximation, which is used to discuss the qualitative features of the protein
      equilibrium distributions as a function of the biological parameters in the fast
      mRNA regime. The performance of the time-scale approximation is assessed by
      comparison with simulations of the full stochastic system, and a good
      quantitative agreement is found for a wide range of parameter values. We show
      that either unimodal or bimodal equilibrium protein distributions can arise, and
      we discuss the autoregulation mechanisms associated with bimodality.

PMID- 23005134
TI  - General aspects of hydrodynamic interactions between three-sphere low-Reynolds
      number swimmers.
AB  - We investigate hydrodynamic interactions between two three-sphere swimmers
      analytically and numerically. Hydrodynamic forces exerted on the swimmers as well
      as the translational and angular velocities of them are obtained in the far field
      regime. We demonstrate that the active term of the translational velocity is
      along the intrinsic direction of swimming (n) and has no component along the
      direction of relative positions of swimmers (r[over ]) as reported in previous
      papers. Using numerical simulations we investigate the long-time swimming paths
      of swimmers in two general situations of swimming in the same and opposite
      directions. The former reveals four swimming states for symmetric swimmers
      attractive, repulsive, parallel, and oscillatory-and only three swimming states
      for asymmetric swimmers-attractive, repulsive, and contracting-oscillatory,
      confirming that the expanding-oscillatory state reported in previous papers is
      not stable. The latter shows that there are rotative bound states in hydrodynamic
      scattering of the swimmers.

PMID- 23005135
TI  - Stochastic modeling of regulation of gene expression by multiple small RNAs.
AB  - A wealth of new research has highlighted the critical roles of small noncoding
      RNAs (sRNAs) in diverse processes, such as quorum sensing and cellular responses
      to stress. The pathways controlling these processes often have a central motif
      composed of a master regulator protein whose expression is controlled by multiple
      sRNAs. However, the stochastic gene expression of a single target gene regulated
      by multiple sRNAs is currently not well understood. To address this issue, we
      analyze a stochastic model of regulation of gene expression by multiple sRNAs.
      For this model, we derive exact analytic results for the regulated protein
      distribution, including compact expressions for its mean and variance. The
      derived results provide insights into the roles of multiple sRNAs in fine-tuning
      the noise in gene expression. In particular, we show that, in contrast to
      regulation by a single sRNA, multiple sRNAs provide a mechanism for independently
      controlling the mean and variance of the regulated protein distribution.

PMID- 23005138
TI  - Phase space approach for modeling of epileptic dynamics.
AB  - Epileptic electroencephalography recordings can be described in terms of four
      prototypic wave forms: fast sinusoidal oscillations, large slow waves, fast
      spiking, and spike waves. On the macroscopic level, these wave forms have been
      modeled by different mechanistic models which share canonical features. Here we
      derive a minimal model of excitatory and inhibitory processes with features
      common to all previous models. We can infer that at least three interacting
      processes are required to support the prototypic epileptic dynamics. Based on a
      separation of time scales we analyze the model in terms of interacting manifolds
      in phase space. This allows qualitative reverse engineering of all epileptic wave
      forms and transitions between them. We propose this method as a complement to
      traditional approaches to modeling epileptiform rhythms.

PMID- 23005137
TI  - Bistable collective behavior of polymers tethered in a nanopore.
AB  - Polymer-coated pores play a crucial role in nucleo-cytoplasmic transport and in a
      number of biomimetic and nanotechnological applications. Here we present Monte
      Carlo and Density Functional Theory approaches to identify different collective
      phases of end-grafted polymers in a nanopore and to study their relative
      stability as a function of intermolecular interactions. Over a range of system
      parameters that is relevant for nuclear pore complexes, we observe two distinct
      phases: one with the bulk of the polymers condensed at the wall of the pore, and
      the other with the polymers condensed along its central axis. The relative
      stability of these two phases depends on the interpolymer interactions. The
      existence the two phases suggests a mechanism in which marginal changes in these
      interactions, possibly induced by nuclear transport receptors, cause the pore to
      transform between open and closed configurations, which will influence transport
      through the pore.

PMID- 23005136
TI  - Optimal diffusion coefficient estimation in single-particle tracking.
AB  - Single-particle tracking is increasingly used to extract quantitative parameters
      on single molecules and their environment, while advances in spatial and temporal
      resolution of tracking techniques inspire new questions and avenues of
      investigation. Correspondingly, sophisticated analytical methods are constantly
      developed to obtain more refined information from measured trajectories. Here we
      point out some fundamental limitations of these approaches due to the finite
      length of trajectories, the presence of localization error, and motion blur,
      focusing on the simplest motion regime of free diffusion in an isotropic medium
      (Brownian motion). We show that two recently proposed algorithms approach the
      theoretical limit of diffusion coefficient uncertainty. We discuss the practical
      performance of the algorithms as well as some important implications of these
      results for single-particle tracking.

PMID- 23005139
TI  - Population density approach for discrete mRNA distributions in generalized
      switching models for stochastic gene expression.
AB  - We present a generalization of a population density approach for modeling and
      analysis of stochastic gene expression. In the model, the gene of interest
      fluctuates stochastically between an inactive state, in which transcription
      cannot occur, and an active state, in which discrete transcription events occur;
      and the individual mRNA molecules are degraded stochastically in an independent
      manner. This sort of model in simplest form with exponential dwell times has been
      used to explain experimental estimates of the discrete distribution of random
      mRNA copy number. In our generalization, the random dwell times in the inactive
      and active states, T_{0} and T_{1}, respectively, are independent random
      variables drawn from any specified distributions. Consequently, the probability
      per unit time of switching out of a state depends on the time since entering that
      state. Our method exploits a connection between the fully discrete random process
      and a related continuous process. We present numerical methods for computing
      steady-state mRNA distributions and an analytical derivation of the mRNA
      autocovariance function. We find that empirical estimates of the steady-state
      mRNA probability mass function from Monte Carlo simulations of laboratory data do
      not allow one to distinguish between underlying models with exponential and
      nonexponential dwell times in some relevant parameter regimes. However, in these
      parameter regimes and where the autocovariance function has negative lobes, the
      autocovariance function disambiguates the two types of models. Our results
      strongly suggest that temporal data beyond the autocovariance function is
      required in general to characterize gene switching.

PMID- 23005140
TI  - Stochastic description of single nucleosome repositioning by ACF remodelers.
AB  - Chromatin remodeling plays a crucial role in the activation or repression of
      transcription of eukaryotic genes. The chromatin remodeler ACF acts as a dimeric,
      processive motor to evenly space nucleosomes, favoring repression of gene
      transcription. Single-molecule experiments have established that ACF moves the
      nucleosome more efficiently towards the longer flanking DNA than towards the
      shorter flanking DNA, thereby centering an initially ill-positioned nucleosome on
      DNA substrates. In this paper we present a one-motor model with nucleosomal
      repositioning rates dependent on the DNA flanking length. The corresponding
      master equation is solved analytically with experimentally relevant parameter
      values. The velocity profile and the effective diffusion constant for nucleosome
      sliding, computed from the probability distributions, are in accordance with
      available experimental data. In order to address the observed kinetic pauses in
      experimental Forster Resonance Energy Transfer profiles, we extend the master
      equation to account for transitions between explicit motor states, i.e.,
      adenosine triphosphate (ATP) loading and ATP hydrolysis in both ACF motors. The
      results of this extended two-motor model are compared to the previous effective
      one-motor model and allow insights into the role of the synchronization of the
      two motors acting on the nucleosome.

PMID- 23005141
TI  - Contributions to membrane-embedded-protein diffusion beyond hydrodynamic
      theories.
AB  - The diffusion coefficients of proteins embedded in a lipid membrane are
      traditionally described by the hydrodynamic Saffman-Delbruck theory, which
      predicts a weak dependence of the diffusion coefficient on protein radius, D~lnR.
      Recent experiments have observed a stronger dependence, D~1/R. This has led to
      speculation that the primary sources of drag on the protein are not hydrodynamic,
      but originate in coupling to other fields, such as lipid chain stretching or
      tilt. We discuss a generic model of a protein coupled to a nonconserved scalar
      order parameter (e.g., chain stretching), and show that earlier results may not
      be as universal as previously believed. In particular, we note that the drag
      depends on the way the protein-order parameter coupling is imposed. In this
      model, D~1/R can be obtained if the protein is much larger than the order
      parameter correlation length. However, if we modify the model to include
      advection of the order parameter, which is a more appropriate assumption for a
      fluid membrane, we find that the entrainment of the order parameter by the
      protein's motion significantly changes the scaling of the diffusion coefficient.
      For parameters appropriate to protein diffusion, the Saffman-Delbruck-like
      scaling is restored, but with an effective radius for the protein that depends on
      the order parameter's correlation length. This qualitative difference suggests
      that hydrodynamic effects cannot be neglected in the computation of drag on a
      protein interacting with the membrane.

PMID- 23005142
TI  - Vesicle dynamics under weak flows: application to large excess area.
AB  - Dynamics of a vesicle under simple shear flow is studied in the limit of small
      capillary number. A perturbative approach is used to derive the equation of
      vesicle dynamics. The expansions are shown to converge for significantly deflated
      vesicles (with excess area from the sphere as high as 2). In particular, we
      provide an explicit analytical expression for the tank-treading to tumbling
      bifurcation point. This expression is valid for excess areas up to 2.5. The
      results are compared with full 3D numerical simulations. The proposed method can
      be used for analytical or numerical solution of vesicle dynamics under weak flow
      of general form.

PMID- 23005144
TI  - Clonal selection prevents tragedy of the commons when neighbors compete in a rock
      paper-scissors game.
AB  - The rock-paper-scissors game is a model example of the ongoing cyclic turnover
      typical of many ecosystems, ranging from the terrestrial and aquatic to the
      microbial. Here we explore the evolution of a rock-paper-scissors system where
      three species compete for space. The species are allowed to mutate and change the
      speed by which they invade one another. In the case when all species have similar
      mutation rates, we observe a perpetual arms race where no single species
      prevails. When only two species mutate, their aggressions increase indefinitely
      until the ecosystem collapses and only the nonmutating species survives. Finally
      we show that when only one species mutates, group selection removes individual
      predators with the fastest growth rates, causing the growth rate of the species
      to stabilize. We explain this group selection quantitatively.

PMID- 23005143
TI  - Effective-medium theory of elastic waves in random networks of rods.
AB  - We formulate an effective medium (mean field) theory of a material consisting of
      randomly distributed nodes connected by straight slender rods, hinged at the
      nodes. Defining wavelength-dependent effective elastic moduli, we calculate both
      the static moduli and the dispersion relations of ultrasonic longitudinal and
      transverse elastic waves. At finite wave vector k the waves are dispersive, with
      phase and group velocities decreasing with increasing wave vector. These results
      are directly applicable to networks with empty pore space. They also describe the
      solid matrix in two-component (Biot) theories of fluid-filled porous media. We
      suggest the possibility of low density materials with higher ratios of stiffness
      and strength to density than those of foams, aerogels, or trabecular bone.

PMID- 23005145
TI  - Distribution of counterions and interaction between two similarly charged
      dielectric slabs: roles of charge discreteness and dielectric inhomogeneity.
AB  - The distribution of counterions and the electrostatic interaction between two
      similarly charged dielectric slabs is studied in the strong coupling limit.
      Dielectric inhomogeneities and discreteness of charge on the slabs have been
      taken into account. It is found that the amount of dielectric constant difference
      between the slabs and the environment, and the discreteness of charge on the
      slabs have opposing effects on the equilibrium distribution of the counterions.
      At small interslab separations, increasing the amount of dielectric constant
      difference increases the tendency of the counterions toward the middle of the
      intersurface space between the slabs and the discreteness of charge pushes them
      to the surfaces of the slabs. In the limit of point charges, independent of the
      strength of dielectric inhomogeneity, counterions distribute near the surfaces of
      the slabs. The interaction between the slabs is attractive at low temperatures
      and its strength increases with the dielectric constant difference. At room
      temperature, the slabs may completely attract each other, reach to an equilibrium
      separation, or have two equilibrium separations with a barrier in between,
      depending on the system parameters.

PMID- 23005146
TI  - Network-of-queues approach to B-cell-receptor affinity discrimination.
AB  - The immune system is one of the most complex signal processing machineries in
      biology. The adaptive immune system, consisting of B and T lymphocytes, is
      activated in response to a large spectrum of pathogen antigens. B cells recognize
      and bind the antigen through B-cell receptors (BCRs) and this is fundamental for
      B-cell activation. However, the system response is dependent on BCR-antigen
      affinity values that span several orders of magnitude. Moreover, the ability of
      the BCR to discriminate between affinities at the high end (e.g., 10^{9}M^{-1}
      10^{10}M^{-1}) challenges the formulation of a mathematical model able to
      robustly separate these affinity-dependent responses. Queuing theory enables the
      analysis of many related processes, such as those resulting from the
      stochasticity of protein binding and unbinding events. Here we define a network
      of queues, consisting of BCR early signaling states and transition rates related
      to the propensity of molecular aggregates to form or disassemble. By considering
      the family of marginal distributions of BCRs in a given signaling state, we
      report a significant separation (measured as Jensen-Shannon divergence) that
      arises from a broad spectrum of antigen affinities.

PMID- 23005147
TI  - Molecular spiders on a plane.
AB  - Synthetic biomolecular spiders with "legs" made of single-stranded segments of
      DNA can move on a surface covered by single-stranded segments of DNA called
      substrates when the substrate DNA is complementary to the leg DNA. If the motion
      of a spider does not affect the substrates, the spider behaves asymptotically as
      a random walk. We study the diffusion coefficient and the number of visited sites
      for spiders moving on the square lattice with a substrate in each lattice site.
      The spider's legs hop to nearest-neighbor sites with the constraint that the
      distance between any two legs cannot exceed a maximal span. We establish analytic
      results for bipedal spiders, and investigate multileg spiders numerically. In
      experimental realizations legs usually convert substrates into products (visited
      sites). The binding of legs to products is weaker, so the hopping rate from the
      substrates is smaller. This makes the problem non-Markovian and we investigate it
      numerically. We demonstrate the emergence of a counterintuitive behavior-the more
      spiders are slowed down on unvisited sites, the more motile they become.

PMID- 23005148
TI  - Critical points of the O(n) loop model on the martini and the 3-12 lattices.
AB  - We derive the critical line of the O(n) loop model on the martini lattice as a
      function of the loop weight n basing on the critical points on the honeycomb
      lattice conjectured by Nienhuis [Phys. Rev. Lett. 49, 1062 (1982)]. In the limit
      n->0 we prove the connective constant MU=1.7505645579? of self-avoiding walks on
      the martini lattice. A finite-size scaling analysis based on transfer matrix
      calculations is also performed. The numerical results coincide with the
      theoretical predictions with a very high accuracy. Using similar numerical
      methods, we also study the O(n) loop model on the 3-12 lattice. We obtain
      similarly precise agreement with the critical points given by Batchelor [J. Stat.
      Phys. 92, 1203 (1998)].

PMID- 23005149
TI  - Avoiding dark states in open quantum systems by tailored initializations.
AB  - We study the transport of excitations on a network of three coupled two-level
      systems that are subjected to an environment that induces incoherent hopping
      between the nodes. The two end nodes are coupled to a source while the central
      node is coupled to a drain. A common feature of these networks is the existence
      of a dark state that blocks the transport to the drain. Here we propose a means
      to avoid this state by a suitable initialization of the system, induced by a
      source that is common to both coupled nodes.

PMID- 23005150
TI  - Nonequilibrium phase transitions and violent relaxation in the Hamiltonian mean
      field model.
AB  - We discuss the nature of nonequilibrium phase transitions in the Hamiltonian mean
      field model using detailed numerical simulations of the Vlasov equation and
      molecular dynamics. Starting from fixed magnetization water bag initial
      distributions and varying the energy, the states obtained after a violent
      relaxation undergo a phase transition from magnetized to nonmagnetized states
      when going from lower to higher energies. The phase transitions are either first
      order or are composed of a cascade of phase reentrances. This result is at
      variance with most previous results in the literature mainly based on the Lynden
      Bell theory of violent relaxation. The latter is a rough approximation and,
      consequently, is not suited for an accurate description of nonequilibrium phase
      transition in long-range interacting systems.

PMID- 23005151
TI  - Computational evidence of two driving mechanisms for overcharging in an electric
      double layer near the point of zero charge.
AB  - We have adopted an ensemble Monte Carlo simulation method to systematically
      verify two physical driving mechanisms responsible for overcharging which refers
      to the adsorption of an effective charge onto a like-charged planar surface
      around the point of zero charge within the primitive model of mixed electrolytes
      with varying salt concentrations. One is electrostatic in character dominated by
      dielectric images and the other is purely entropic in origin by ionic size
      asymmetry effects, of which the former has never been reported both theoretically
      and experimentally and the latter could be interpreted satisfactorily in terms of
      available theoretical approaches. The electrostatically driven mechanism is found
      to critically depend on the ionic sizes while the entropically driven mechanism
      occurs with almost the same efficiency in a relative wide range of surface charge
      density. Depending on the delicate interplay between charge and steric
      correlations, the two distinct driving mechanisms may cooperatively give rise to
      a more pronounced overcharging process.

PMID- 23005152
TI  - Selective adsorption of lattice peptides on patterned surfaces.
AB  - To study the adsorption of individual peptides in implicit solvent, we propose a
      version of the Wang-Landau Monte Carlo algorithm that uses a single surface, with
      no need for a confining wall or grafting. Our "wall-free" method is both more
      efficient than the traditional ones and free of additional assumptions or
      approximations. We illustrate it by simulating an HP-model lattice peptide on
      planar surfaces with a variety of patterns of adsorption sites, discovering a
      temperature-induced switch of surface selection which is due to a balance of
      energetic and entropic effects.

PMID- 23005153
TI  - Detecting hidden nodes in complex networks from time series.
AB  - We develop a general method to detect hidden nodes in complex networks, using
      only time series from nodes that are accessible to external observation. Our
      method is based on compressive sensing and we formulate a general framework
      encompassing continuous- and discrete-time and the evolutionary-game type of
      dynamical systems as well. For concrete demonstration, we present an example of
      detecting hidden nodes from an experimental social network. Our paradigm for
      detecting hidden nodes is expected to find applications in a variety of fields
      where identifying hidden or black-boxed objects based on a limited amount of data
      is of interest.

PMID- 23005154
TI  - Anomalous scaling and large-scale anisotropy in magnetohydrodynamic turbulence:
      two-loop renormalization-group analysis of the Kazantsev-Kraichnan kinematic
      model.
AB  - The field theoretic renormalization group and operator product expansion are
      applied to the Kazantsev-Kraichnan kinematic model for the magnetohydrodynamic
      turbulence. The anomalous scaling emerges as a consequence of the existence of
      certain composite fields ("operators") with negative dimensions. The anomalous
      exponents for the correlation functions of arbitrary order are calculated in the
      two-loop approximation (second order of the renormalization-group expansion),
      including the anisotropic sectors. The anomalous scaling and the hierarchy of
      anisotropic contributions become stronger due to those second-order
      contributions.

PMID- 23005155
TI  - Relativistic x-ray free-electron lasers in the quantum regime.
AB  - We present a nonlinear theory for relativistic x-ray free-electron lasers in the
      quantum regime, using a collective Klein-Gordon (KG) equation (for relativistic
      electrons), which is coupled with the Maxwell-Poisson equations for the
      electromagnetic and electrostatic fields. In our model, an intense
      electromagnetic wave is used as a wiggler which interacts with a relativistic
      electron beam to produce coherent tunable radiation. The KG-Maxwell-Poisson model
      is used to derive a general nonlinear dispersion relation for parametric
      instabilities in three space dimensions, including an arbitrarily large amplitude
      electromagnetic wiggler field. The nonlinear dispersion relation reveals the
      importance of quantum recoil effects and oblique scattering of the radiation that
      can be tuned by varying the beam energy.

PMID- 23005156
TI  - Time-varying priority queuing models for human dynamics.
AB  - Queuing models provide insight into the temporal inhomogeneity of human dynamics,
      characterized by the broad distribution of waiting times of individuals
      performing tasks. We theoretically study the queuing model of an agent trying to
      execute a task of interest, the priority of which may vary with time due to the
      agent's "state of mind." However, its execution is disrupted by other tasks of
      random priorities. By considering the priority of the task of interest either
      decreasing or increasing algebraically in time, we analytically obtain and
      numerically confirm the bimodal and unimodal waiting time distributions with
      power-law decaying tails, respectively. These results are also compared to the
      updating time distribution of papers in arXiv.org and the processing time
      distribution of papers in Physical Review journals. Our analysis helps to
      understand human task execution in a more realistic scenario.

PMID- 23005157
TI  - Chasing and escaping by three groups of species.
AB  - We study group chasing and escaping between three species. In our model, one
      species acts as a group of chasers for another species and acts as a group of
      targets for the third species. When a particle is caught by a target, the
      particle becomes a new chaser. Although the ratio of three species is changed,
      the total number of particles is conserved. When particles move randomly, the
      numbers of the three species change periodically but no species seems to become
      extinct. If particles escape from the nearest chaser and chase the nearest
      target, the extinction of a species occurs. The extinction induces that of the
      second species and finally only one species survives.

PMID- 23005158
TI  - Range-limited centrality measures in complex networks.
AB  - Here we present a range-limited approach to centrality measures in both
      nonweighted and weighted directed complex networks. We introduce an efficient
      method that generates for every node and every edge its betweenness centrality
      based on shortest paths of lengths not longer than l=1,...,L in the case of
      nonweighted networks, and for weighted networks the corresponding quantities
      based on minimum weight paths with path weights not larger than w(l)=lDelta,
      l=1,2...,L=R/Delta. These measures provide a systematic description on the
      positioning importance of a node (edge) with respect to its network neighborhoods
      one step out, two steps out, etc., up to and including the whole network. They
      are more informative than traditional centrality measures, as network transport
      typically happens on all length scales, from transport to nearest neighbors to
      the farthest reaches of the network. We show that range-limited centralities obey
      universal scaling laws for large nonweighted networks. As the computation of
      traditional centrality measures is costly, this scaling behavior can be exploited
      to efficiently estimate centralities of nodes and edges for all ranges, including
      the traditional ones. The scaling behavior can also be exploited to show that the
      ranking top list of nodes (edges) based on their range-limited centralities
      quickly freezes as a function of the range, and hence the diameter-range top list
      can be efficiently predicted. We also show how to estimate the typical largest
      node-to-node distance for a network of N nodes, exploiting the afore-mentioned
      scaling behavior. These observations were made on model networks and on a large
      social network inferred from cell-phone trace logs (~5.5*10(6) nodes and
      ~2.7*10(7) edges). Finally, we apply these concepts to efficiently detect the
      vulnerability backbone of a network (defined as the smallest percolating cluster
      of the highest betweenness nodes and edges) and illustrate the importance of
      weight-based centrality measures in weighted networks in detecting such
      backbones.

PMID- 23005159
TI  - Expectation-driven migration promotes cooperation by group interactions.
AB  - "Voting with feet" describes the prominent social phenomenon that people tend to
      move away from deteriorating neighborhoods and search for and join prosperous
      groups. To quantify the role this kind of expectation-driven migration plays in
      the evolution of cooperation, here we study a simple yet effective model of
      cooperation based on spatial public goods games. The population structure is
      characterized by a square lattice with some nodes being left empty. Individuals
      have expectations toward their current habitats. Dissatisfied players, whose
      expectation is not met after interacting with all directly connected neighbors,
      tend to abstain from the groups of low quality by moving away and explore the
      physical niches of avail. How fast interaction happens relatively to selection is
      regulated by the time-scale ratio of game interaction to natural selection. Under
      strong selection, simulation results show that cooperation is greatly improved
      for either low, moderate, or high expectations compared to whenever the
      expectation-driven migration is absent. Further explorations reveal that neither
      too high nor too low but rather a combination of moderate expectations and rapid
      interaction establishes cooperation for a moderate public goods enhancement
      factor. There exists an optimal interval of expectation level most favoring the
      evolution of cooperation as the required time-scale ratio is minimized.

PMID- 23005160
TI  - Error and attack vulnerability of temporal networks.
AB  - The study of real-world communication systems via complex network models has
      greatly expanded our understanding on how information flows, even in completely
      decentralized architectures such as mobile wireless networks. Nonetheless, static
      network models cannot capture the time-varying aspects and, therefore, various
      temporal metrics have been introduced. In this paper, we investigate the
      robustness of time-varying networks under various failures and intelligent
      attacks. We adopt a methodology to evaluate the impact of such events on the
      network connectivity by employing temporal metrics in order to select and remove
      nodes based on how critical they are considered for the network. We also define
      the temporal robustness range, a new metric that quantifies the disruption caused
      by an attack strategy to a given temporal network. Our results show that in real
      world networks, where some nodes are more dominant than others, temporal
      connectivity is significantly more affected by intelligent attacks than by random
      failures. Moreover, different intelligent attack strategies have a similar effect
      on the robustness: even small subsets of highly connected nodes act as a
      bottleneck in the temporal information flow, becoming critical weak points of the
      entire system. Additionally, the same nodes are the most important across a range
      of different importance metrics, expressing the correlation between highly
      connected nodes and those that trigger most of the changes in the optimal
      information spreading. Contrarily, we show that in randomly generated networks,
      where all the nodes have similar properties, random errors and intelligent
      attacks exhibit similar behavior. These conclusions may help us in design of more
      robust systems and fault-tolerant network architectures.

PMID- 23005161
TI  - Model reduction for agent-based social simulation: coarse-graining a civil
      violence model.
AB  - Agent-based modeling (ABM) constitutes a powerful computational tool for the
      exploration of phenomena involving emergent dynamic behavior in the social
      sciences. This paper demonstrates a computer-assisted approach that bridges the
      significant gap between the single-agent microscopic level and the macroscopic
      (coarse-grained population) level, where fundamental questions must be rationally
      answered and policies guiding the emergent dynamics devised. Our approach will be
      illustrated through an agent-based model of civil violence. This spatiotemporally
      varying ABM incorporates interactions between a heterogeneous population of
      citizens [active (insurgent), inactive, or jailed] and a population of police
      officers. Detailed simulations exhibit an equilibrium punctuated by periods of
      social upheavals. We show how to effectively reduce the agent-based dynamics to a
      stochastic model with only two coarse-grained degrees of freedom: the number of
      jailed citizens and the number of active ones. The coarse-grained model captures
      the ABM dynamics while drastically reducing the computation time (by a factor of
      approximately 20).

PMID- 23005162
TI  - Quantifying the complexity of random Boolean networks.
AB  - We study two measures of the complexity of heterogeneous extended systems, taking
      random Boolean networks as prototypical cases. A measure defined by Shalizi et
      al. for cellular automata, based on a criterion for optimal statistical
      prediction [Shalizi et al., Phys. Rev. Lett. 93, 118701 (2004)], does not
      distinguish between the spatial inhomogeneity of the ordered phase and the
      dynamical inhomogeneity of the disordered phase. A modification in which
      complexities of individual nodes are calculated yields vanishing complexity
      values for networks in the ordered and critical regimes and for highly disordered
      networks, peaking somewhere in the disordered regime. Individual nodes with high
      complexity are the ones that pass the most information from the past to the
      future, a quantity that depends in a nontrivial way on both the Boolean function
      of a given node and its location within the network.

PMID- 23005163
TI  - Universal relation between skewness and kurtosis in complex dynamics.
AB  - We identify an important correlation between skewness and kurtosis for a broad
      class of complex dynamic systems and present a specific analysis of earthquake
      and financial time series. Two regimes of non-Gaussianity can be identified: a
      parabolic one, which is common in various fields of physics, and a power law one,
      with exponent 4/3, which at the moment appears to be specific of earthquakes and
      financial markets. For this property we propose a model and an interpretation in
      terms of very rare events dominating the statistics independently on the nature
      of the events considered. The predicted scaling relation between skewness and
      kurtosis matches very well the experimental pattern of the second regime.
      Regarding price fluctuations, this situation characterizes a universal stylized
      fact.

PMID- 23005164
TI  - Epidemics on interconnected networks.
AB  - Populations are seldom completely isolated from their environment. Individuals in
      a particular geographic or social region may be considered a distinct network due
      to strong local ties but will also interact with individuals in other networks.
      We study the susceptible-infected-recovered process on interconnected network
      systems and find two distinct regimes. In strongly coupled network systems,
      epidemics occur simultaneously across the entire system at a critical infection
      strength beta(c), below which the disease does not spread. In contrast, in weakly
      coupled network systems, a mixed phase exists below beta(c) of the coupled
      network system, where an epidemic occurs in one network but does not spread to
      the coupled network. We derive an expression for the network and disease
      parameters that allow this mixed phase and verify it numerically. Public health
      implications of communities comprising these two classes of network systems are
      also mentioned.

PMID- 23005165
TI  - Features and heterogeneities in growing network models.
AB  - Many complex networks from the World Wide Web to biological networks grow taking
      into account the heterogeneous features of the nodes. The feature of a node might
      be a discrete quantity such as a classification of a URL document such as
      personal page, thematic website, news, blog, search engine, social network, etc.,
      or the classification of a gene in a functional module. Moreover the feature of a
      node can be a continuous variable such as the position of a node in the embedding
      space. In order to account for these properties, in this paper we provide a
      generalization of growing network models with preferential attachment that
      includes the effect of heterogeneous features of the nodes. The main effect of
      heterogeneity is the emergence of an "effective fitness" for each class of nodes,
      determining the rate at which nodes acquire new links. The degree distribution
      exhibits a multiscaling behavior analogous to the the fitness model. This
      property is robust with respect to variations in the model, as long as links are
      assigned through effective preferential attachment. Beyond the degree
      distribution, in this paper we give a full characterization of the other relevant
      properties of the model. We evaluate the clustering coefficient and show that it
      disappears for large network size, a property shared with the Barabasi-Albert
      model. Negative degree correlations are also present in this class of models,
      along with nontrivial mixing patterns among features. We therefore conclude that
      both small clustering coefficients and disassortative mixing are outcomes of the
      preferential attachment mechanism in general growing networks.

PMID- 23005166
TI  - Spread of infectious diseases in directed and modular metapopulation networks.
AB  - We consider epidemics in metapopulations on different network topologies. Recent
      work on epidemics on networks has focused on epidemics of humans. In this work we
      present a model for epidemics on directed networks, which are found, for example,
      in the livestock trade. We show that the direction of edges and the modular
      structure of networks have an impact on the outbreak size and the time of the
      outbreak peak. In some circumstances, the outbreak size in directed networks can
      even be larger than in undirected systems. The results presented here could be
      useful for decision-making processes in directed modular systems.

PMID- 23005167
TI  - Analytical models for well-mixed populations of cooperators and defectors under
      limiting resources.
AB  - In the study of the evolution of cooperation, resource limitations are usually
      assumed just to provide a finite population size. Recently, however, agent-based
      models have pointed out that resource limitation may modify the original
      structure of the interactions and allow for the survival of unconditional
      cooperators in well-mixed populations. Here, we present analytical simplified
      versions of two types of agent-based models recently published: one in which the
      limiting resource constrains the ability of reproduction of individuals but not
      their survival, and a second one where the limiting resource is necessary for
      both reproduction and survival. One finds that the analytical models display,
      with a few differences, the same qualitative behavior of the more complex agent
      based models. In addition, the analytical models allow us to expand the study and
      identify the dimensionless parameters governing the final fate of the system,
      such as coexistence of cooperators and defectors, or dominance of defectors or of
      cooperators. We provide a detailed analysis of the occurring phase transitions as
      these parameters are varied.

PMID- 23005168
TI  - Opinion group formation and dynamics: structures that last from nonlasting
      entities.
AB  - We extend simple opinion models to obtain stable but continuously evolving
      communities. Our scope is to meet a challenge raised by sociologists of
      generating "structures that last from nonlasting entities." We achieve this by
      introducing two kinds of noise on a standard opinion model. First, agents may
      interact with other agents even if their opinion difference is large. Second,
      agents randomly change their opinion at a constant rate. We show that for a large
      range of control parameters, our model yields stable and fluctuating polarized
      states, where the composition and mean opinion of the emerging groups is
      fluctuating over time.

PMID- 23005169
TI  - Community identification in networks with unbalanced structure.
AB  - Community (module) structure is a common and important property of many types of
      networks, such as social networks and biological networks. Several classes of
      algorithms have been proposed for community structure detection and
      identification, including clustering techniques, modularity optimization, and
      other methods. Among these methods, the modularity optimization method has
      attracted a great deal of attention and much related research has been published.
      However, the existing modularity optimization method does not perform well in the
      presence of unbalanced community structures. In this paper, we introduce a metric
      to characterize the community structure better than other metrics in this
      situation, and we propose a method to infer the number of communities, which may
      solve the resolution limit problem. We then develop an algorithm for community
      structure identification based on eigendecompositions, and we give both simulated
      and real data examples to illustrate the better performance of our approach.

PMID- 23005170
TI  - Nonperturbative model for wrinkling in highly bendable sheets.
AB  - The wrinkled geometry of thin films is known to vary appreciably as the applied
      stresses exceed their buckling threshold. Here we derive and analyze a minimal,
      nonperturbative set of equations that captures the continuous evolution of radial
      wrinkles in the simplest axisymmetric geometry from threshold to the far-from
      threshold limit, where the compressive stress collapses. This description of the
      growth of wrinkles is different from the traditional post-buckling approach and
      is expected to be valid for highly bendable sheets. Numerical analysis of our
      model predicts two surprising results. First, the number of wrinkles scales
      anomalously with the thickness of the sheet and the exerted load, in apparent
      contradiction with previous predictions. Second, there exists an invariant
      quantity that characterizes the mutual variation of the amplitude and number of
      wrinkles from threshold to the far-from-threshold regime.

PMID- 23005171
TI  - Eigenvalue spectra of asymmetric random matrices for multicomponent neural
      networks.
AB  - This paper focuses on large neural networks whose synaptic connectivity matrices
      are randomly chosen from certain random matrix ensembles. The dynamics of these
      networks can be characterized by the eigenvalue spectra of their connectivity
      matrices. In reality, neurons in a network do not necessarily behave in a similar
      way, but may belong to several different categories. The first study of the
      spectra of two-component neural networks was carried out by Rajan and Abbott
      [Phys. Rev. Lett. 97, 188104 (2006)]. In their model, neurons are either
      "excitatory" or "inhibitory," and strengths of synapses from different types of
      neurons have Gaussian distributions with different means and variances. A
      surprising finding by Rajan and Abbott is that the eigenvalue spectra of these
      types of random synaptic matrices do not depend on the mean values of their
      elements. In this paper we prove that this is true even for a much more general
      type of random neural network, where there is a finite number of types of neurons
      and their synaptic strengths have correlated distributions. Furthermore, using
      the diagrammatic techniques, we calculate the explicit formula for the spectra of
      synaptic matrices of multicomponent neural networks.

PMID- 23005172
TI  - Fragmentation transitions in multistate voter models.
AB  - Adaptive models of opinion formation among humans can display a fragmentation
      transition, where a social network breaks into disconnected components. Here we
      investigate this transition in a class of models with arbitrary number of
      opinions. In contrast to previous work we do not assume that opinions are
      equidistant or arranged on a one-dimensional conceptual axis. Our investigation
      reveals detailed analytical results on fragmentations in a three-opinion model,
      which are confirmed by agent-based simulations. Furthermore, we show that in
      certain models the number of opinions can be reduced without affecting the
      fragmentation points.

PMID- 23005173
TI  - Communities and bottlenecks: trees and treelike networks have high modularity.
AB  - Much effort has gone into understanding the modular nature of complex networks.
      Communities, also known as clusters or modules, are typically considered to be
      densely interconnected groups of nodes that are only sparsely connected to other
      groups in the network. Discovering high quality communities is a difficult and
      important problem in a number of areas. The most popular approach is the
      objective function known as modularity, used both to discover communities and to
      measure their strength. To understand the modular structure of networks it is
      then crucial to know how such functions evaluate different topologies, what
      features they account for, and what implicit assumptions they may make. We show
      that trees and treelike networks can have unexpectedly and often arbitrarily high
      values of modularity. This is surprising since trees are maximally sparse
      connected graphs and are not typically considered to possess modular structure,
      yet the nonlocal null model used by modularity assigns low probabilities, and
      thus high significance, to the densities of these sparse tree communities. We
      further study the practical performance of popular methods on model trees and on
      a genealogical data set and find that the discovered communities also have very
      high modularity, often approaching its maximum value. Statistical tests reveal
      the communities in trees to be significant, in contrast with known results for
      partitions of sparse, random graphs.

PMID- 23005174
TI  - Existence and significance of communities in the World Trade Web.
AB  - The World Trade Web (WTW), which models the international transactions among
      countries, is a fundamental tool for studying the economics of trade flows, their
      evolution over time, and their implications for a number of phenomena, including
      the propagation of economic shocks among countries. In this respect, the possible
      existence of communities is a key point, because it would imply that countries
      are organized in groups of preferential partners. In this paper, we use four
      approaches to analyze communities in the WTW between 1962 and 2008, based,
      respectively, on modularity optimization, cluster analysis, stability functions,
      and persistence probabilities. Overall, the four methods agree in finding no
      evidence of significant partitions. A few weak communities emerge from the
      analysis, but they do not represent secluded groups of countries, as
      intercommunity linkages are also strong, supporting the view of a truly
      globalized trading system.

PMID- 23005175
TI  - Self-similar solutions to a density-dependent reaction-diffusion model.
AB  - In this paper, we investigated a density-dependent reaction-diffusion equation,
      u(t)=(u(m))(xx)+u-u(m). This equation is known as the extension of the Fisher or
      Kolmogoroff-Petrovsky-Piscounoff equation, which is widely used in population
      dynamics, combustion theory, and plasma physics. By employing a suitable
      transformation, this equation was mapped to the anomalous diffusion equation
      where the nonlinear reaction term was eliminated. Due to its simpler form, some
      exact self-similar solutions with compact support have been obtained. The
      solutions, evolving from an initial state, converge to the usual traveling wave
      at a certain transition time. Hence, the connection between the self-similar
      solution and the traveling wave solution is quite clear from these results.
      Moreover, the solutions were found in a manner that propagates either to the
      right or to the left. Furthermore, the two solutions form a symmetric solution,
      expanding in both directions. Applications to spatiotemporal pattern formation in
      biological populations is discussed.

PMID- 23005176
TI  - Analysis of power-law exponents by maximum-likelihood maps.
AB  - Maximum-likelihood exponent maps have been studied as a technique to increase the
      understanding and improve the fit of power-law exponents to experimental and
      numerical simulation data, especially when they exhibit both upper and lower
      cutoffs. The use of the technique is tested by analyzing seismological data,
      acoustic emission data, and avalanches in numerical simulations of the three
      dimensional random field Ising model. In the different examples we discuss the
      nature of the deviations observed in the exponent maps and some relevant
      conclusions are drawn for the physics behind each phenomenon.

PMID- 23005177
TI  - Complex networks in the Euclidean space of communicability distances.
AB  - We study the properties of complex networks embedded in a Euclidean space of
      communicability distances. The communicability distance between two nodes is
      defined as the difference between the weighted sum of walks self-returning to the
      nodes and the weighted sum of walks going from one node to the other. We give
      some indications that the communicability distance identifies the least crowded
      routes in networks where simultaneous submission of packages is taking place. We
      define an index Q based on communicability and shortest path distances, which
      allows reinterpreting the "small-world" phenomenon as the region of minimum Q in
      the Watts-Strogatz model. It also allows the classification and analysis of
      networks with different efficiency of spatial uses. Consequently, the
      communicability distance displays unique features for the analysis of complex
      networks in different scenarios.

PMID- 23005178
TI  - Locating privileged spreaders on an online social network.
AB  - Social media have provided plentiful evidence of their capacity for information
      diffusion. Fads and rumors but also social unrest and riots travel fast and
      affect large fractions of the population participating in online social networks
      (OSNs). This has spurred much research regarding the mechanisms that underlie
      social contagion, and also who (if any) can unleash system-wide information
      dissemination. Access to real data, both regarding topology--the network of
      friendships--and dynamics--the actual way in which OSNs users interact, is
      crucial to decipher how the former facilitates the latter's success, understood
      as efficiency in information spreading. With the quantitative analysis that stems
      from complex network theory, we discuss who (and why) has privileged spreading
      capabilities when it comes to information diffusion. This is done considering the
      evolution of an episode of political protest which took place in Spain, spanning
      one month in 2011.

PMID- 23005179
TI  - Detecting correlations among functional-sequence motifs.
AB  - Sequence motifs are words of nucleotides in DNA with biological functions, e.g.,
      gene regulation. Identification of such words proceeds through rejection of
      Markov models on the expected motif frequency along the genome. Additional
      biological information can be extracted from the correlation structure among
      patterns of motif occurrences. In this paper a log-linear multivariate intensity
      Poisson model is estimated via expectation maximization on a set of motifs along
      the genome of E. coli K12. The proposed approach allows for excitatory as well as
      inhibitory interactions among motifs and between motifs and other genomic
      features like gene occurrences. Our findings confirm previous stylized facts
      about such types of interactions and shed new light on genome-maintenance
      functions of some particular motifs. We expect these methods to be applicable to
      a wider set of genomic features.

PMID- 23005180
TI  - Rare-region effects in the contact process on networks.
AB  - Networks and dynamical processes occurring on them have become a paradigmatic
      representation of complex systems. Studying the role of quenched disorder, both
      intrinsic to nodes and topological, is a key challenge. With this in mind, here
      we analyze the contact process (i.e., the simplest model for propagation
      phenomena) with node-dependent infection rates (i.e., intrinsic quenched
      disorder) on complex networks. We find Griffiths phases and other rare-region
      effects, leading rather generically to anomalously slow (algebraic, logarithmic,
      etc.) relaxation, on Erdos-Renyi networks. We predict similar effects to exist
      for other topologies as long as a nonvanishing percolation threshold exists. More
      strikingly, we find that Griffiths phases can also emerge--even with constant
      epidemic rates--as a consequence of mere topological heterogeneity. In
      particular, we find Griffiths phases in finite-dimensional networks as, for
      instance, a family of generalized small-world networks. These results have a
      broad spectrum of implications for propagation phenomena and other dynamical
      processes on networks, and are relevant for the analysis of both models and
      empirical data.

PMID- 23005181
TI  - Analytical approach to the model of scientific revolutions.
AB  - The model of scientific paradigms spreading throughout a community of agents with
      memory is analyzed using the master equation. The case of two competing ideas is
      considered for various networks of interactions, including agents placed at Erdos
      Renyi graphs or complete graphs. The pace of adopting a new idea by the community
      is analyzed, along with the distribution of periods after which a new idea
      replaces the old one. The approach is extended for the chain topology to the more
      general case when more than two ideas compete. Our analytical results agree with
      the numerical simulations.

PMID- 23005182
TI  - Measures of centrality based on the spectrum of the Laplacian.
AB  - We introduce a family of new centralities, the k-spectral centralities. k
      spectral centrality is a measurement of importance with respect to the
      deformation of the graph Laplacian associated with the graph. Due to this
      connection, k-spectral centralities have various interpretations in terms of
      spectrally determined information. We explore this centrality in the context of
      several examples. While for sparse unweighted networks 1-spectral centrality
      behaves similarly to other standard centralities, for dense weighted networks
      they show different properties. In summary, the k-spectral centralities provide a
      novel and useful measurement of relevance (for single network elements as well as
      whole subnetworks) distinct from other known measures.

PMID- 23005183
TI  - Quantitative analysis of pedestrian counterflow in a cellular automaton model.
AB  - Pedestrian dynamics exhibits various collective phenomena. Here, we study
      bidirectional pedestrian flow in a floor field cellular automaton model. Under
      certain conditions, lane formation is observed. Although it has often been
      studied qualitatively, e.g., as a test for the realism of a model, there are
      almost no quantitative results, either empirically or theoretically. As basis for
      a quantitative analysis, we introduce an order parameter which is adopted from
      the analysis of colloidal suspensions. This allows us to determine a phase
      diagram for the system where four different states (free flow, disorder, lanes,
      gridlock) can be distinguished. Although the number of lanes formed is
      fluctuating, lanes are characterized by a typical density. It is found that the
      basic floor field model overestimates the tendency towards a gridlock compared to
      experimental bounds. Therefore, an anticipation mechanism is introduced which
      reduces the jamming probability.

PMID- 23005184
TI  - Time-dependent wave selection for information processing in excitable media.
AB  - We demonstrate an improved technique for implementing logic circuits in light
      sensitive chemical excitable media. The technique makes use of the constant-speed
      propagation of waves along defined channels in an excitable medium based on the
      Belousov-Zhabotinsky reaction, along with the mutual annihilation of colliding
      waves. What distinguishes this work from previous work in this area is that
      regions where channels meet at a junction can periodically alternate between
      permitting the propagation of waves and blocking them. These valvelike areas are
      used to select waves based on the length of time that it takes waves to propagate
      from one valve to another. In an experimental implementation, the channels that
      make up the circuit layout are projected by a digital projector connected to a
      computer. Excitable channels are projected as dark areas and unexcitable regions
      as light areas. Valves alternate between dark and light: Every valve has the same
      period and phase, with a 50% duty cycle. This scheme can be used to make logic
      gates based on combinations of or and and-not operations, with few geometrical
      constraints. Because there are few geometrical constraints, compact circuits can
      be implemented. Experimental results from an implementation of a four-bit input,
      two-bit output integer square root circuit are given.

PMID- 23005185
TI  - Enhancing network robustness against malicious attacks.
AB  - In a recent work [Schneider et al., Proc. Natl. Acad. Sci. USA 108, 3838 (2011)],
      the authors proposed a simple measure for network robustness under malicious
      attacks on nodes. Using a greedy algorithm, they found that the optimal structure
      with respect to this quantity is an onion structure in which high-degree nodes
      form a core surrounded by rings of nodes with decreasing degree. However, in real
      networks the failure can also occur in links such as dysfunctional power cables
      and blocked airlines. Accordingly, complementary to the node-robustness
      measurement (R(n)), we propose a link-robustness index (R(l)). We show that
      solely enhancing R(n) cannot guarantee the improvement of R(l). Moreover, the
      structure of an R(l)-optimized network is found to be entirely different from
      that of an onion network. In order to design robust networks that are resistant
      to a more realistic attack condition, we propose a hybrid greedy algorithm that
      takes both the R(n) and R(l) into account. We validate the robustness of our
      generated networks against malicious attacks mixed with both nodes and links
      failure. Finally, some economical constraints for swapping the links in real
      networks are considered, and significant improvement in both aspects of
      robustness is still achieved.

PMID- 23005186
TI  - Statistical properties of avalanches in networks.
AB  - We characterize the distributions of size and duration of avalanches propagating
      in complex networks. By an avalanche we mean the sequence of events initiated by
      the externally stimulated excitation of a network node, which may, with some
      probability, then stimulate subsequent excitations of the nodes to which it is
      connected, resulting in a cascade of excitations. This type of process is
      relevant to a wide variety of situations, including neuroscience, cascading
      failures on electrical power grids, and epidemiology. We find that the statistics
      of avalanches can be characterized in terms of the largest eigenvalue and
      corresponding eigenvector of an appropriate adjacency matrix that encodes the
      structure of the network. By using mean-field analyses, previous studies of
      avalanches in networks have not considered the effect of network structure on the
      distribution of size and duration of avalanches. Our results apply to individual
      networks (rather than network ensembles) and provide expressions for the
      distributions of size and duration of avalanches starting at particular nodes in
      the network. These findings might find application in the analysis of branching
      processes in networks, such as cascading power grid failures and critical brain
      dynamics. In particular, our results show that some experimental signatures of
      critical brain dynamics (i.e., power-law distributions of size and duration of
      neuronal avalanches) are robust to complex underlying network topologies.

PMID- 23005187
TI  - Regulation of Turing patterns in a spatially extended chlorine-iodine-malonic
      acid system with a local concentration-dependent diffusivity.
AB  - A chlorine-iodine-malonic-acid Turing system involving a local concentration
      dependent diffusivity (LCDD) has fundamental significance for physical, chemical,
      and biological systems with inhomogeneous medium. We investigated such a system
      by both numerical computation and mathematical analysis. Our research reveals
      that a variable local diffusivity has an evident effect on regulating the Turing
      patterns for different modes. An intrinsic square-root law is given by lambda ~
      (c(1)+c(2)k)(1/2), which relates the pattern wavelength (lambda) with the LCDD
      coefficient (k). This law indicates that the system pattern has the properties of
      an equivalent Turing pattern. The current study confirms that, for the Turing
      system with LCDD, the system pattern form retains the basic characteristics of a
      traditional Turing pattern in a wide range of LCDD coefficients.

PMID- 23005188
TI  - Impact of generalized benefit functions on the evolution of cooperation in
      spatial public goods games with continuous strategies.
AB  - Cooperation and defection may be considered to be two extreme responses to a
      social dilemma. Yet the reality is much less clear-cut. Between the two extremes
      lies an interval of ambivalent choices, which may be captured theoretically by
      means of continuous strategies defining the extent of the contributions of each
      individual player to the common pool. If strategies are chosen from the unit
      interval, where 0 corresponds to pure defection and 1 corresponds to the maximal
      contribution, the question is what is the characteristic level of individual
      investments to the common pool that emerges if the evolution is guided by
      different benefit functions. Here we consider the steepness and the threshold as
      two parameters defining an array of generalized benefit functions, and we show
      that in a structured population there exist intermediate values of both at which
      the collective contributions are maximal. However, as the cost-to-benefit ratio
      of cooperation increases, the characteristic threshold decreases while the
      corresponding steepness increases. Our observations remain valid if more complex
      sigmoid functions are used, thus reenforcing the importance of carefully adjusted
      benefits for high levels of public cooperation.

PMID- 23005189
TI  - Robustness of a network formed by n interdependent networks with a one-to-one
      correspondence of dependent nodes.
AB  - Many real-world networks interact with and depend upon other networks. We develop
      an analytical framework for studying a network formed by n fully interdependent
      randomly connected networks, each composed of the same number of nodes N. The
      dependency links connecting nodes from different networks establish a unique one
      to-one correspondence between the nodes of one network and the nodes of the other
      network. We study the dynamics of the cascades of failures in such a network of
      networks (NON) caused by a random initial attack on one of the networks, after
      which a fraction p of its nodes survives. We find for the fully interdependent
      loopless NON that the final state of the NON does not depend on the dynamics of
      the cascades but is determined by a uniquely defined mutual giant component of
      the NON, which generalizes both the giant component of regular percolation of a
      single network (n=1) and the recently studied case of the mutual giant component
      of two interdependent networks (n=2). We also find that the mutual giant
      component does not depend on the topology of the NON and express it in terms of
      generating functions of the degree distributions of the network. Our results show
      that, for any n>=2 there exists a critical p=p(c)>0 below which the mutual giant
      component abruptly collapses from a finite nonzero value for p>=p(c) to zero for
      p<p(c), as in a first-order phase transition. This behavior holds even for scale
      free networks where p(c)=0 for n=1. We show that, if at least one of the networks
      in the NON has isolated or singly connected nodes, the NON completely
      disintegrates for sufficiently large n even if p=1. In contrast, in the absence
      of such nodes, the NON survives for any n for sufficiently large p. We illustrate
      this behavior by comparing two exactly solvable examples of NONs composed of
      Erdos-Renyi (ER) and random regular (RR) networks. We find that the robustness of
      n coupled RR networks of degree k is dramatically higher compared to the n
      coupled ER networks of the same average degree k[over -]=k. While for ER NONs
      there exists a critical minimum average degree k[over -]=k[over -](min)~lnn below
      which the system collapses, for RR NONs k(min)=2 for any n (i.e., for any k>2, a
      RR NON is stable for any n with p(c)<1). This results arises from the critical
      role played by singly connected nodes which exist in an ER NON and enhance the
      cascading failures, but do not exist in a RR NON.

PMID- 23005190
TI  - One-dimensional lattice of oscillators coupled through power-law interactions:
      continuum limit and dynamics of spatial Fourier modes.
AB  - We study synchronization in a system of phase-only oscillators residing on the
      sites of a one-dimensional periodic lattice. The oscillators interact with a
      strength that decays as a power law of the separation along the lattice length
      and is normalized by a size-dependent constant. The exponent alpha of the power
      law is taken in the range 0<=alpha<1. The oscillator frequency distribution is
      symmetric about its mean (taken to be zero) and is nonincreasing on [0,infinity).
      In the continuum limit, the local density of oscillators evolves in time
      following the continuity equation that expresses the conservation of the number
      of oscillators of each frequency under the dynamics. This equation admits as a
      stationary solution the unsynchronized state uniform both in phase and over the
      space of the lattice. We perform a linear stability analysis of this state to
      show that when it is unstable, different spatial Fourier modes of fluctuations
      have different stability thresholds beyond which they grow exponentially in time
      with rates that depend on the Fourier modes. However, numerical simulations show
      that at long times all the nonzero Fourier modes decay in time, while only the
      zero Fourier mode (i.e., the "mean-field" mode) grows in time, thereby dominating
      the instability process and driving the system to a synchronized state. Our
      theoretical analysis is supported by extensive numerical simulations.

PMID- 23005191
TI  - Width of the chaotic layer: maxima due to marginal resonances.
AB  - Modern theoretical methods for estimating the width of the chaotic layer in the
      presence of prominent marginal resonances are considered in the perturbed
      pendulum model of nonlinear resonance. The fields of applicability of these
      methods are explicitly and precisely formulated. The comparative accuracy is
      investigated in massive and long-run numerical experiments. It is shown that the
      methods are naturally subdivided in classes applicable for adiabatic and
      nonadiabatic cases of perturbation. It is explicitly shown that the pendulum
      approximation of marginal resonance works well in the nonadiabatic case. In this
      case, the role of marginal resonances in determining the total layer width is
      demonstrated to diminish with increasing main parameter lambda (equal to the
      ratio of the perturbation frequency to the frequency of small-amplitude phase
      oscillations on the resonance). Solely the "bending effect" is important in
      determining the total amplitude of the energy deviations of the near-separatrix
      motion at lambda?7. In the adiabatic case, it is demonstrated that the
      geometrical form of the separatrix cell can be described analytically quite
      easily by means of using a specific representation of the separatrix map. It is
      shown that the nonadiabatic (and, to some extent, intermediary) case is most
      actual, in comparison with the adiabatic one, for the physical or technical
      applications that concern the energy jumps in the near-separatrix chaotic motion.

PMID- 23005192
TI  - Synchronization of many nanomechanical resonators coupled via a common cavity
      field.
AB  - Using amplitude equations, we show that groups of identical nanomechanical
      resonators, interacting with a common mode of a cavity microwave field,
      synchronize to form a single mechanical mode which couples to the cavity with a
      strength dependent on the squared sum of the individual mechanical-microwave
      couplings. Classically this system is dominated by periodic behavior which, when
      analyzed using amplitude equations, can be shown to exhibit multistability. In
      contrast, groups of sufficiently dissimilar nanomechanical oscillators may lose
      synchronization and oscillate out of phase at significantly higher amplitudes.
      Further, the method by which synchronization is lost resembles that for large
      amplitude forcing which is not of the Kuramoto form.

PMID- 23005193
TI  - Transient features of quantum open maps.
AB  - We study families of open chaotic maps that classically share the same asymptotic
      properties--forward and backward trapped sets, repeller dimensions, and escape
      rate--but differ in their short time behavior. When these maps are quantized we
      find that the fine details of the distribution of resonances and the
      corresponding eigenfunctions are sensitive to the initial shape and size of the
      openings. We study phase space localization of the resonances with respect to the
      repeller and find strong delocalization effects when the area of the openings is
      smaller than h.

PMID- 23005194
TI  - Delayed double ionization as a signature of Hamiltonian chaos.
AB  - We analyze the dynamical processes behind delayed double ionization of atoms
      subjected to strong laser pulses. Using reduced models, we show that these
      processes are a signature of Hamiltonian chaos which results from the competition
      between the laser field and the Coulomb attraction to the nucleus. In particular,
      we exhibit the paramount role of the unstable manifold of selected periodic
      orbits which lead to a delay in these double ionizations. Among delayed double
      ionizations, we consider the case of recollision excitation with subsequent
      ionization (RESI) and, as a hallmark of this mechanism, we predict oscillations
      in the ratio of RESI to double ionization yields versus laser intensity. We
      discuss the significance of the dimensionality of the reduced models for the
      analysis of the dynamical processes behind delayed double ionization.

PMID- 23005195
TI  - Generation of polygonal soliton clusters and fundamental solitons in dissipative
      systems by necklace-ring beams with radial-azimuthal phase modulation.
AB  - We demonstrate that, in a two-dimensional dissipative medium described by the
      cubic-quintic (CQ) complex Ginzburg-Landau (CGL) equation with the viscous
      (spectral-filtering) term, necklace rings carrying a mixed radial-azimuthal phase
      modulation can evolve into polygonal or quasipolygonal stable soliton clusters,
      and into stable fundamental solitons. The outcome of the evolution is controlled
      by the depth and azimuthal anharmonicity of the phase-modulation profile, or by
      the radius and number of "beads" in the initial necklace ring. Threshold
      characteristics of the evolution of the patterns are identified and explained.
      Parameter regions for the formation of the stable polygonal and quasipolygonal
      soliton clusters, and of stable fundamental solitons, are identified. The model
      with the CQ terms replaced by the full saturable nonlinearity produces
      essentially the same set of basic dynamical scenarios; hence this set is a
      universal one for the CGL models.

PMID- 23005196
TI  - Impulse-induced optimum control of escape from a metastable state by periodic
      secondary excitations.
AB  - We characterize the role of the impulse transmitted (time integral over a half
      period) by resonant secondary excitations at controlling (suppressing and
      enhancing) escape from a potential well, which is induced by periodic primary
      excitations. By using the universal model of a dissipative Helmholtz oscillator,
      we demonstrate numerically that optimum control of escape occurs when the impulse
      transmitted by the chaos-controlling excitations is maximum while keeping their
      amplitude and period fixed. These findings are in complete agreement with
      analytical predictions from two independent methods: Melnikov analysis and energy
      based analysis. Additional numerical results corresponding to other alternative
      escape-controlling excitations demonstrate the generality of the essential role
      of the excitation's impulse.

PMID- 23005197
TI  - Synchronous patterns in complex systems.
AB  - When a complex network is slightly desynchronized, a few of the network nodes
      will be escaping from the uniform synchronization background frequently with a
      random fashion, leading to the intermittent network synchronization. Here, based
      on the eigenvectors of the network coupling matrix, we propose a new method which
      is able to figure out the unstable nodes in the general case of desynchronized
      complex networks. Moreover, with this method, we are also able to regulate the
      seemingly random network dynamics into stable and visible synchronous patterns.
      The efficiency of this method is verified by a variety of network models,
      including varying the network structures, the node local dynamics, and the
      desynchronization types. Our studies show that, even for the complex network
      systems, synchronous patterns can still be identified and characterized.

PMID- 23005198
TI  - Frequency structure of the nonlinear instability of a dragged viscous thread.
AB  - A thread of viscous fluid falling onto a moving surface exhibits a spectacular
      variety of types of motion as the surface speed and nozzle height are varied. For
      modest nozzle heights, four clear regimes are observed. For large surface speed,
      the thread is dragged into a stretched centenary configuration which is confined
      to a plane. As the surface speed is lowered, the thread exhibits a supercritical
      bifurcation to a meandering state. At very low surface speeds, the state
      resembles the usual coiling motion of a viscous thread falling on a stationary
      surface. In between the meandering and coiling regimes, a window containing a
      novel multifrequency state, previously called "figures of eight," is found. Using
      an improved visualization technique and a fully automated apparatus, we made
      detailed measurements of the longitudinal and transverse motion of the thread in
      all these states. We found that the multifrequency state is characterized by a
      complex pattern of motion whose main frequencies are locked in a 3:2 ratio. This
      state appears and disappears with finite amplitude at sharp bifurcations without
      measurable hysteresis.

PMID- 23005199
TI  - Biased diffusion inside regular islands under random symplectic perturbations.
AB  - We study the random concatenation of slightly different two-dimensional
      Hamiltonian maps with a mixed phase space. We consider a regular island whose
      fixed point is identical for all maps. Trajectories of the concatenated maps near
      this fixed point are no longer confined to invariant tori. We derive a stochastic
      model for the distance from the fixed point, which turns out to be a biased
      random walk with multiplicative noise. We give an analytical prediction of the
      survival probability of trajectories inside the regular island, which
      asymptotically is the product of a power law and an exponential. We confirm these
      results numerically for the parametrically perturbed standard map.

PMID- 23005200
TI  - Anomalous coalescence in sheared two-dimensional foam.
AB  - We report an experimental study on shearing a monolayer of monodisperse bubbles
      floating on liquid in a narrow-gap Couette device. The bubbles in such a "bubble
      raft" coalesce only if the shear rate exceeds a threshold value. This is in
      contrast to the conventional wisdom that bubbles and drops coalesce for gentler
      collisions, at shear rates below a critical value. Furthermore, the threshold
      shear rate increases with the bubble size and the viscosity of the suspending
      liquid, contravening reasoning based on capillary number. Through visualization
      and scaling arguments, we investigate several plausible mechanisms for the
      anomalous coalescence. None explains all aspects of the observations. The most
      promising model is one based on inertial forces that compress the bubbles
      radially inward and accelerate film drainage.

PMID- 23005201
TI  - Time-dependent Poiseuille flow of a viscous compressible fluid confined between
      two planar walls with dynamic partial slip boundary condition.
AB  - Time-dependent Poiseuille flow of a viscous compressible fluid confined between
      two planar walls is studied for a partial slip boundary condition with frequency
      dependent slip length. After an initial uniform impulse parallel to the walls,
      the flow pattern quickly becomes nearly parabolic. For a narrow gap, a dynamic
      slip length can lead to damped oscillations of total fluid momentum.

PMID- 23005202
TI  - Analytical approximations for the collapse of an empty spherical bubble.
AB  - The Rayleigh equation 3/2R+RR+prho(-1)=0 with initial conditions R(0)=R(0),
      R(0)=0 models the collapse of an empty spherical bubble of radius R(T) in an
      ideal, infinite liquid with far-field pressure p and density rho. The solution
      for r=R/R(0) as a function of time t=T/T(c), where R(T(c))=0, is independent of
      R(0), p, and rho. While no closed-form expression for r(t) is known, we find that
      r(0)(t)=(1-t(2))(2/5) approximates r(t) with an error below 1%. A systematic
      development in orders of t(2) further yields the 0.001% approximation
      r(*)(t)=r(0)(t)[1-a(1)Li(2.21)(t(2))], where a(1)~-0.01832099 is a constant and
      Li is the polylogarithm. The usefulness of these approximations is demonstrated
      by comparison to high-precision cavitation data obtained in microgravity.

PMID- 23005203
TI  - Low-Reynolds-number swimmer utilizing surface traveling waves: analytical and
      experimental study.
AB  - Microscale slender swimmers are frequently encountered in nature and are now used
      in microrobotic applications. The swimming mechanism examined in this paper is
      based on small transverse axisymmetric traveling wave deformations of a
      cylindrical long shell. The thin-shelled device is assumed to be inextensible at
      the middle surface and extensible at the surface wetted by the fluid. Assuming
      low-Reynolds-number hydrodynamics, an analytical solution is derived for waves of
      small amplitudes compared with the cylinder diameter. We show that swimming
      velocity increases with beta(1) (the ratio of cylinder radius to wavelength) and
      that swimming velocity is linearly dependent on wave propagation velocity,
      increasing to leading order with the square of the ratio of wave amplitude to
      wavelength beta(2) and decreasing with the wall thickness. A fourth-order
      correction in beta(2) was also calculated and was found to have a negative effect
      on the swimming velocity. The results for a shell of negligible-wall thickness
      were compared with Taylor's solution for an inextensible two-dimensional flat
      membrane undergoing a waving motion and Felderhof's results [Phys. Fluids 22,
      113604 (2010)] for an unbounded flow field and negligible-wall thickness. We show
      that Taylor's analytic solution is a particular limiting case of the present
      solution, assuming zero wall thickness and infinite values of beta(1). The
      present mechanism was also compared with Taylor's well known solutions of waving
      planar and helical circular tails. We show that the present approach yields
      higher velocities as beta(1) increases, whereas, the opposite occurs for waving
      tails. Indeed, in the region where beta(1)>15, the present approach yields
      velocities nearly as fast as Taylor's helical waving tail while consuming less
      power and with a design that is considerably more compact. In this regime, the
      axisymmetric swimmer is twice as fast as Taylor's planar-tail swimmer for an
      additional investment of only one-third of the power. Experiments were conducted
      using a macroscale autonomous model immersed in highly viscous silicone fluid. We
      outlined how the proposed mechanism was realized to propel an elongated, yet
      finite, swimmer. Measured data demonstrate the effects of wave velocity and
      wavelength on swimming speed, showing good agreement with analytical results.

PMID- 23005204
TI  - Instabilities in a horizontal liquid layer in cocurrent gas flow with an
      evaporating interface.
AB  - The problem of a two-layer system consisting of a horizontal liquid layer in
      contact with its own vapor is considered. The liquid layer is bounded by a rigid
      wall from below, and phase change can occur at the interface. The flow of the
      vapor phase is driven by a constant pressure gradient in the streamwise
      direction. We have taken into account the effects of buoyancy, thermocapillarity,
      evaporation, and the dynamics of the vapor phase. A full linear stability
      analysis is performed using a Chebyshev spectral method. The influences of
      evaporation effect and the interfacial shear on the Rayleigh instability and the
      Marangoni instability have been studied. The results show that both the
      evaporation and the interfacial shear play important roles in the stability of
      the system.

PMID- 23005205
TI  - Onset of convective instabilities in under-ice melt ponds.
AB  - The onset of double-diffusive natural convection in under-ice melt ponds is
      investigated through a linear stability analysis. The three-layer configuration
      is composed by a fluid layer (melt pond) overlying a saturated porous medium (ice
      matrix), which in turn overlies another fluid layer (under-ice melt pond). Water
      density inversion is taken into account by adopting a density profile with a
      quadratic temperature dependence and a linear concentration dependence. We show
      that the key parameter affecting stability is the depth of the ice matrix, while
      the depths of the upper and lower fluid layers play a marginal role. A Hopf
      bifurcation is observed in the whole range of parameters studied, and the size of
      the convection cells depends on ice permeability. The influence of the external
      temperature gradient is investigated by means of the definition of an extra
      thermal parameter accounting for the relative position of the density maximum. It
      is shown that convection is favored by larger temperature gradients, which occur
      during Arctic summer.

PMID- 23005206
TI  - Shock velocity increase due to a heterogeneity produced by a two-gas layer.
AB  - Shock tube experiments are performed in order to study shock propagation along a
      two-gas layer in a confined geometry and to compare it to the case of a
      homogeneous density equivalent mixture. The analysis of the homogeneous case
      gives values for the adiabatic coefficient and density of the mixture of both
      gases, while the comparison between heterogeneous and homogeneous media with the
      same averaged density shows modifications of the shock front shape and velocity.
      In the two-gas layer, the shock propagates faster than in the homogeneous medium.
      The shock front is curved with a triple point which appears close to the shock
      tube wall, in the slow medium, while it stays planar during its whole propagation
      in the homogeneous mixture. A correlation is found between the angle of curvature
      and the shock velocity increase. It is confirmed by two-dimensional Eulerian
      numerical calculations. Experiments and calculations exhibit very good agreement
      on all the measurements when molecular diffusion is taken into account in the
      numerical calculations. A sustained irregular refraction pattern of the shock
      front at the diffuse interface of both gases is obtained experimentally and
      confirmed by the calculations.

PMID- 23005207
TI  - Laminar-turbulent cycles in inclined lock-exchange flows.
AB  - We consider strongly confined, stably stratified shear flows generated as a lock
      exchange in a tube inclined at an angle of theta=45(?). This paper focuses on a
      transitional regime, in which the flow alternates between two distinct states:
      laminar, parallel shear flow and intense transverse motion characteristic of
      turbulence. Laminar-turbulent cycles were captured at Atwood numbers At=(rho(2)
      rho(1))/(rho(1)+rho(2)) ranging from 2.45*10(-3) to 4.0*10(-3), where
      (rho(1),rho(2)) are the initial densities of the two fluids, with multiple cycles
      observed at At=2.55*10(-3). The evolution of the density and velocity fields in
      these flows was measured simultaneously using laser-induced fluorescence and
      particle image velocimetry. During each laminar-turbulent cycle, the axial
      velocity exhibits a distinctive ramp-cliff pattern, indicating that the flow
      accelerates as it relaminarizes, then decelerates rapidly as the Kelvin-Helmholtz
      billows break down. Within the range of experimental conditions, transverse
      stratification does not directly determine the onset of instability. Instead, the
      data suggest that a necessary criterion for the onset of instability is for the
      local Reynolds number to exceed 2200, with only a weak dependence on the
      Richardson number.

PMID- 23005208
TI  - Nonlinear dynamic behavior of microscopic bubbles near a rigid wall.
AB  - The nonlinear dynamic behavior of microscopic bubbles near a rigid wall is
      investigated. Oscillations are driven by the ultrasonic pressure field that
      arises in various biomedical applications such as ultrasound imaging or targeted
      drug delivery. It is known that, when bubbles approach a blood-vessel wall, their
      linear dynamic response is modified. This modification may be very useful for
      real-time detection of bubbles that have found targets; in future therapeutic
      technologies, it may be useful for controlled release of medical agents
      encapsulating microbubbles. In this paper, the nonlinear response of microbubbles
      near a wall is studied. The Keller-Miksis-Parlitz equation is adopted, but
      modified to account for the presence of a rigid wall. This base model describes
      the time evolution of the bubble surface, which is assumed to remain spherical,
      and accounts for the effect of acoustic radiation losses owing to liquid
      compressibility in the momentum conservation. Two situations are considered: the
      base case of an isolated bubble in an unbounded medium, and a bubble near a rigid
      wall. In the latter case, the wall influence is modeled by including a
      symmetrically oscillating image bubble. The bubble dynamics is traced using a
      numerical solution of the model equation. Subsequently, Floquet theory is used to
      accurately detect the bifurcation point where bubble oscillations stop following
      the driving ultrasound frequency and undergo period-changing bifurcations. Of
      particular interest is the detection of the subcritical period-tripling and 
      quadrupling transition. The parametric bifurcation maps are obtained as functions
      of nondimensional parameters representing the bubble radius, the frequency and
      pressure amplitude of the driving ultrasound field, and the distance from the
      wall. It is shown that the presence of the wall generally stabilises the bubble
      dynamics, so that much larger values of the pressure amplitude are needed to
      generate nonlinear responses. Thus, a clinical protocol in which selected
      nonlinear harmonics are examined under varying insonation amplitudes may be
      useful in detecting microbubble proximity to walls.

PMID- 23005209
TI  - Hydrodynamic drag-force measurement and slip length on microstructured surfaces.
AB  - In this paper, a drainage experiment of water between a borosilicate sphere and a
      microstructured surface constituted by regularly spaced pillars is presented. The
      microstructured surface has two parts: on one part the liquid forms a Cassie
      interface and on the second it forms a Wenzel interface. The measured
      hydrodynamic drag force is larger on the Cassie part compared to the Wenzel part.
      Furthermore, for the Cassie part, from the hydrodynamic drag force measurements
      on a pillar and between pillars the corresponding local slip lengths have been
      extracted. The area average slip length on the surface is in agreement with the
      value expected by Philip's equation.

PMID- 23005210
TI  - Decay of capillary wave turbulence.
AB  - We report on the observation of freely decaying capillary wave turbulence on the
      surface of a fluid. The capillary wave turbulence spectrum decay is found to be
      self-similar in time with the same power law exponent as the one found in the
      stationary regime, in agreement with weak turbulence predictions. The amplitude
      of all Fourier modes are found to decrease exponentially with time at the same
      damping rate. The longest wavelengths involved in the system are shown to be
      damped by a viscous surface boundary layer. These long waves play the role of an
      energy source during the decay that sustains nonlinear interactions to keep
      capillary waves in a wave turbulent state.

PMID- 23005211
TI  - Structure of drying fronts in three-dimensional porous media.
AB  - Evaporation in a three-dimensional (3D) porous medium, a sand column saturated by
      water, was studied using synchrotron x-ray tomography. Three-dimensional images
      of the medium with a resolution of 7 MUm were obtained during the evaporation.
      The entire column was scanned seven times, resulting in nearly 10(4) 2D cross
      sections and illustrating the spatial distribution of air, liquid, and solid
      phases at the pore scale. The results were analyzed in order to gain new insights
      and better understanding of the characteristics of the drying front that was
      formed when the liquid-filled pores were invaded by air, as well as the structure
      of the liquid phase as it was dried. The analysis indicates that the liquid phase
      has a self-similar fractal structure, with its fractal dimension D(f) in all the
      cross sections being a function of the water content or saturation. In addition,
      D(f) for the 3D liquid structure, as well as its density correlation function,
      were computed using the 3D images. A crossover length scale xi was identified
      that separates the fractal regime from the compact geometry. For length scales
      r>xi, the density correlation function approaches asymptotically the water
      content of the porous medium. The drying front is shown to be rough and multi
      affine, rather than self-affine. Its properties were also computed using the 3D
      images. The roughness characteristics agree with those for imbibition in porous
      media, but not with those of fracture surfaces and crack lines.

PMID- 23005212
TI  - Examination of the four-fifths law for longitudinal third-order moments in
      incompressible magnetohydrodynamic turbulence in a periodic box.
AB  - The four-fifths law for third-order longitudinal moments is examined, using
      direct numerical simulation (DNS) data on three-dimensional (3D) forced
      incompressible magnetohydrodynamic (MHD) turbulence without a uniformly imposed
      magnetic field in a periodic box. The magnetic Prandtl number is set to one, and
      the number of grid points is 512(3). A generalized Karman-Howarth-Kolmogorov
      equation for second-order velocity moments in isotropic MHD turbulence is
      extended to anisotropic MHD turbulence by means of a spherical average over the
      direction of r. Here, r is a separation vector. The viscous, forcing, anisotropic
      and nonstationary terms in the generalized equation are quantified. It is found
      that the influence of the anisotropic terms on the four-fifths law is negligible
      at small scales, compared to that of the viscous term. However, the influence of
      the directional anisotropy, which is measured by the departure of the third-order
      moments in a particular direction of r from the spherically averaged ones, on the
      four-fifths law is suggested to be substantial, at least in the case studied
      here.

PMID- 23005213
TI  - Influence of an inhomogeneous internal magnetic field on the flow dynamics of a
      ferrofluid between differentially rotating cylinders.
AB  - The influence of a magnetic field on the dynamics of the flow of a ferrofluid in
      the gap between two concentric, independently rotating cylinders is investigated
      numerically. The Navier-Stokes equations are solved using a hybrid finite
      difference and Galerkin method. We show that the frequently used assumption that
      the internal magnetic field within a ferrofluid is equal to the external applied
      field is only a leading-order approximation. By accounting for the ferrofluid's
      magnetic susceptibility, we show that a uniform externally imposed magnetic field
      is modified by the presence of the ferrofluid within the annulus. The
      modification to the magnetic field has an r(-2) radial dependence and a magnitude
      that scales with the susceptibility. For ferrofluids typically used in laboratory
      experiments of the type simulated in this paper, the modification to the imposed
      magnetic field can be substantial. This has significant consequences on the
      structure and stability of the basic states, as well as on the bifurcating
      solutions.

PMID- 23005214
TI  - Role of large-scale velocity fluctuations in a two-vortex kinematic dynamo.
AB  - This paper presents an analysis of the Dudley-James two-vortex flow, which
      inspired several laboratory-scale liquid-metal experiments, in order to better
      demonstrate its relation to astrophysical dynamos. A coordinate transformation
      splits the flow into components that are axisymmetric and nonaxisymmetric
      relative to the induced magnetic dipole moment. The reformulation gives the flow
      the same dynamo ingredients as are present in more complicated convection-driven
      dynamo simulations. These ingredients are currents driven by the mean flow and
      currents driven by correlations between fluctuations in the flow and fluctuations
      in the magnetic field. The simple model allows us to isolate the dynamics of the
      growing eigenvector and trace them back to individual three-wave couplings
      between the magnetic field and the flow. This simple model demonstrates the
      necessity of poloidal advection in sustaining the dynamo and points to the effect
      of large-scale flow fluctuations in exciting a dynamo magnetic field.

PMID- 23005215
TI  - Transport in fractal media: an effective scale-invariant approach.
AB  - In this paper an advective-dispersion equation with scale-dependent coefficients
      is proposed for describing transport through fractals. This equation is obtained
      by imposing scale invariance and assuming that the porosity, the dispersion
      coefficient, and the velocity follow fractional power laws on the scale. The
      model incorporates the empirically found trends in highly heterogeneous media,
      regarding the dependence of the dispersivity on the scale and the dispersion
      coefficient on the velocity. We conclude that the presence of nontrivial fractal
      parameters produces anomalous dispersion, as expected, and that the presence of
      convective processes induces a reescalation in the concentration and shifts the
      tracer velocity to different values with respect to the nonfractal case.

PMID- 23005216
TI  - Renormalization and universality of blowup in hydrodynamic flows.
AB  - We consider self-similar solutions describing intermittent bursts in shell models
      of turbulence and study their relationship with blowup phenomena in continuous
      hydrodynamic models. First, we show that these solutions are very close to self
      similar solution for the Fourier transformed inviscid Burgers equation
      corresponding to shock formation from smooth initial data. Then, the result is
      generalized to hyperbolic conservation laws in one space dimension describing
      compressible flows. It is shown that the renormalized wave profile tends to a
      universal function, which is independent both of initial conditions and of a
      specific form of the conservation law. This phenomenon can be viewed as a new
      manifestation of the renormalization group theory. Finally, we discuss
      possibilities for application of the developed theory for detecting and
      describing a blowup in incompressible flows.

PMID- 23005217
TI  - Nonmodal stability in Hagen-Poiseuille flow of a shear thinning fluid.
AB  - Linear stability in Hagen-Poiseuille flow of a shear-thinning fluid is
      considered. The non-Newtonian viscosity is described by the Carreau rheological
      law. The effects of shear thinning on the stability are investigated using the
      energy method and the nonmodal stability theory. The energy analysis shows that
      the nonaxisymmetric disturbance with the azimuthal wave number m=1 has the lowest
      critical energy Reynolds number for both the Newtonian and shear-thinning cases.
      With the increase of shear thinning, the critical energy Reynolds number
      decreases for both the axisymmetric and nonaxisymmetric cases. For the nonmodal
      stability, we focus on two problems: response to external excitations and
      response to initial conditions. The former is studied by examining the epsilon
      pseudospectrum, and the latter by examining the energy growth function G(t). For
      both Newtonian and shear-thinning fluids, it is found that there can be a rather
      large transient growth even though the linear operator of the Hagen-Poiseuille
      flow has no unstable eigenvalue. For the problem of response to external
      excitations, the optimal response is achieved by disturbance with m=1 for both
      the Newtonian and non-Newtonian cases. For the problem of response to initial
      conditions, the optimal disturbance is in the form of streamwise uniform streaks.
      Being different from the Newtonian case, the azimuthal wave number of the optimal
      disturbance may be greater than 1 for strongly shear-thinning cases.

PMID- 23005218
TI  - Band gaps and localization of surface water waves over large-scale sand waves
      with random fluctuations.
AB  - Band structure and wave localization are investigated for sea surface water waves
      over large-scale sand wave topography. Sand wave height, sand wave width, water
      depth, and water width between adjacent sand waves have significant impact on
      band gaps. Random fluctuations of sand wave height, sand wave width, and water
      depth induce water wave localization. However, random water width produces a
      perfect transmission tunnel of water waves at a certain frequency so that
      localization does not occur no matter how large a disorder level is applied.
      Together with theoretical results, the field experimental observations in the
      Taiwan Bank suggest band gap and wave localization as the physical mechanism of
      sea surface water wave propagating over natural large-scale sand waves.

PMID- 23005219
TI  - Observability of periodic lines in three-dimensional lid-driven cylindrical
      cavity flows.
AB  - This study employs three-dimensional particle-tracking velocimetry (3D-PTV) for
      experimental investigation of the existence and properties of periodic lines in
      3D lid-driven time-periodic flows inside a cylindrical cavity. These periodic
      lines, consisting of material points that periodically return to their initial
      position, play a central role in the transport properties of laminar flows, yet
      their existence has so far been demonstrated only in numerical simulations. The
      formation and characteristics of periodic lines are inextricably linked with
      spatiotemporal symmetries of the flow. 3D-PTV measurements determined that
      relevant symmetries, identified with previous symmetry analyses, are satisfied
      within experimental error bounds. These measurements subsequently isolated
      periodic lines in the designated symmetry planes, thus offering first
      experimental evidence of their physical existence and their fundamental reliance
      on symmetries. Experimental periodic lines are topologically equivalent to those
      in simulated flows with identical symmetries and exhibit the same response to
      changes in forcing conditions. The laboratory experiments by these observations
      bridge the gap from theoretical and numerical predictions on periodic lines to
      real 3D flows.

PMID- 23005220
TI  - Tunable heat transfer with smart nanofluids.
AB  - Strongly thermophilic nanofluids are able to transfer either small or large
      quantities of heat when subjected to a stable temperature difference. We
      investigate the bistability diagram of the heat transferred by this class of
      nanofluids. We show that bistability can be exploited to obtain a controlled
      switching between a conductive and a convective regime of heat transfer, so as to
      achieve a controlled modulation of the heat flux.

PMID- 23005221
TI  - Anomalous diffusion in confined turbulent convection.
AB  - Turbulent convection in quasi-one-dimensional geometry is studied by means of
      high-resolution direct numerical simulations within the framework of Rayleigh
      Taylor turbulence. Geometrical confinement has dramatic effects on the dynamics
      of the turbulent flow, inducing a transition from superdiffusive to subdiffusive
      evolution of the mixing layer and arresting the growth of kinetic energy. A
      nonlinear diffusion model is shown to reproduce accurately the above
      phenomenology. The model is used to predict, without free parameters, the
      spatiotemporal evolution of the heat flux profile and the dependence of the
      Nusselt number on the Rayleigh number.

PMID- 23005222
TI  - Bounds for the number of degrees of freedom of incompressible magnetohydrodynamic
      turbulence in two and three dimensions.
AB  - We study incompressible magnetohydrodynamic turbulence in both two and three
      dimensions, with an emphasis on the number of degrees of freedom N. This number
      is estimated in terms of the magnetic Prandtl number Pr, kinetic Reynolds number
      Re, and magnetic Reynolds number Rm. Here Re and Rm are dynamic in nature,
      defined in terms of the kinetic and magnetic energy dissipation rates (or
      averages of the velocity and magnetic field gradients), viscosity and magnetic
      diffusivity, and the system size. It is found that for the two-dimensional case,
      N satisfies N<=PrRe(3/2)+Rm(3/2) for Pr>1 and N<=Re(3/2)+Pr(-1)Rm(3/2) for Pr<=1.
      In three dimensions, on the other hand, N satisfies N<=(PrRe(3/2)+Rm(3/2))(3/2)
      for Pr>1 and N<=(Re(3/2)+Pr(-1)Rm(3/2))(3/2) for Pr<=1. In the limit Pr->0,
      Re(3/2) dominates Pr(-1)Rm(3/2), and the present estimate for N appropriately
      reduces to Re(9/4) as in the case of usual Navier-Stokes turbulence. For Pr~1,
      our results imply the classical spectral scaling of the energy inertial range and
      dissipation wave number (in the form of upper bounds). These bounds are
      consistent with the existing predictions in the literature for turbulence with or
      without Alfven wave effects. We discuss the possibility of solution regularity,
      with an emphasis on the two-dimensional case in the absence of either one or both
      of the dissipation terms.

PMID- 23005223
TI  - Cutoff wave number for shear waves and Maxwell relaxation time in Yukawa liquids.
AB  - Because liquids cannot resist shear except over very short distances comparable
      to the atomic spacing, shear sound waves (i.e., transverse phonons) propagate
      only for very short wavelengths. A measure of this limit is the cutoff wave
      number k(c), which is sometimes called the critical wave number. Previously k(c)
      was determined in molecular dynamics (MD) simulations by obtaining the dispersion
      relation. Another approach is developed in this paper by identifying the wave
      number at the onset of a negative peak in the transverse current correlation
      function. This method is demonstrated using a three-dimensional MD simulation of
      a Yukawa fluid, which mimics dusty plasmas. In general, k(c) is an indicator of
      conditions where elastic and dissipative effects are approximately balanced.
      Additionally, the crossover frequency for the real and imaginary terms of the
      complex viscosity of a dusty plasma is obtained; this crossover frequency
      corresponds to the Maxwell relaxation time.

PMID- 23005224
TI  - Frequency-dependent shear viscosity of a liquid two-dimensional dusty plasma.
AB  - The viscoelasticity of a two-dimensional (2D) liquid stronglycoupled dusty plasma
      is studied experimentally, without macroscopic shear. Positions and velocities of
      the dust particles, measured by video microscopy, are used as the inputs to the
      generalized Green-Kubo relation to obtain the complex viscosity eta(omega). The
      real part of eta(omega) (which corresponds to dissipation) diminishes gradually
      with frequency, while the imaginary part (which corresponds to elasticity) is
      peaked at a frequency below the 2D dusty plasma frequency. The viscoelastic
      approximation is found to accurately describe the 2D experimental results for
      eta(omega), yielding the Maxwell relaxation time tau(M)=0.10 s. Results for
      eta(omega) are compared to 2D molecular dynamics Yukawa simulations and to a
      previous experiment that was performed using an oscillating macroscopic shear.

PMID- 23005225
TI  - Collective vibration of discharge current filaments in a self-organized pattern
      within a dielectric barrier discharge.
AB  - We report on the collective vibration of discharge current filaments in a self
      organized superlattice pattern within an air-argon dielectric barrier discharge
      system. The period of collective vibration decreases as the air content
      increases. An antisymmetric normal vibration mode of discharge current filaments
      is observed. The measurements of the spatiotemporal behavior of the superlattice
      pattern show that the discharge of the vibrating dot (filament) is asynchronous
      with that of its eight neighboring dots, including four big dots and four small
      dots. The forces exerted on the vibrating dot are analyzed, and a motion equation
      is set up in each half cycle of the applied voltage. It is found that the motion
      of the small dot is not an ideal vibration but is a vibration with fluctuating
      amplitude, which is in good agreement with experiments.

PMID- 23005226
TI  - Direct molecular dynamics simulation of liquid-solid phase equilibria for two
      component plasmas.
AB  - We determine the liquid-solid phase diagram for carbon-oxygen and oxygen-selenium
      plasma mixtures using two-phase molecular dynamics simulations. We identify
      liquid, solid, and interface regions using a bond angle metric. To study finite
      size effects, we perform 27,648- and 55,296-ion simulations. To help monitor
      nonequilibrium effects, we calculate diffusion constants D(i). For the carbon
      oxygen system we find that D(O) for oxygen ions in the solid is much smaller than
      D(C) for carbon ions and that both diffusion constants are 80 or more times
      smaller than diffusion constants in the liquid phase. There is excellent
      agreement between our carbon-oxygen phase diagram and that predicted by Medin and
      Cumming. This suggests that errors from finite-size and nonequilibrium effects
      are small and that the carbon-oxygen phase diagram is now accurately known. The
      oxygen-selenium system is a simple two-component model for more complex rapid
      proton capture nucleosynthesis ash compositions for an accreting neutron star.
      Diffusion of oxygen, in a predominantly selenium crystal, is remarkably fast,
      comparable to diffusion in the liquid phase. We find a somewhat lower melting
      temperature for the oxygen-selenium system than that predicted by Medin and
      Cumming. This is probably because of electron screening effects.

PMID- 23005227
TI  - Not much helicity is needed to drive large-scale dynamos.
AB  - Understanding the in situ amplification of large-scale magnetic fields in
      turbulent astrophysical rotators has been a core subject of dynamo theory. When
      turbulent velocities are helical, large-scale dynamos that substantially amplify
      fields on scales that exceed the turbulent forcing scale arise, but the minimum
      sufficient fractional kinetic helicity f(h,C) has not been previously well
      quantified. Using direct numerical simulations for a simple helical dynamo, we
      show that f(h,C) decreases as the ratio of forcing to large-scale wave numbers
      k(F)/k(min) increases. From the condition that a large-scale helical dynamo must
      overcome the back reaction from any nonhelical field on the large scales, we
      develop a theory that can explain the simulations. For k(F)/k(min)>=8 we find
      f(h,C)?3%, implying that very small helicity fractions strongly influence
      magnetic spectra for even moderate-scale separation.

PMID- 23005228
TI  - Fluid-solid phase transitions in three-dimensional complex plasmas under
      microgravity conditions.
AB  - Phase behavior of large three-dimensional (3D) complex plasma systems under
      microgravity conditions onboard the International Space Station is investigated.
      The neutral gas pressure is used as a control parameter to trigger phase changes.
      Detailed analysis of structural properties and evaluation of three different
      melting-freezing indicators reveal that complex plasmas can exhibit melting by
      increasing the gas pressure. Theoretical estimates of complex plasma parameters
      allow us to identify main factors responsible for the observed behavior. The
      location of phase states of the investigated systems on a relevant equilibrium
      phase diagram is estimated. Important differences between the melting process of
      3D complex plasmas under microgravity conditions and that of flat 2D complex
      plasma crystals in ground based experiments are discussed.

PMID- 23005229
TI  - Shear flow instability in a strongly coupled dusty plasma.
AB  - Linear stability analysis of strongly coupled incompressible dusty plasma in
      presence of shear flow has been carried out using the generalized hydrodynamical
      (GH) model. With the proper Galilean invariant GH model, a nonlocal eigenvalue
      analysis has been done using different velocity profiles. It is shown that the
      effect of elasticity enhances the growth rate of shear flow driven Kelvin-
      Helmholtz (KH) instability. The interplay between viscosity and elasticity not
      only enhances the growth rate but the spatial domain of the instability is also
      widened. The growth rate in various parameter space and the corresponding
      eigenfunctions are presented.

PMID- 23005230
TI  - Intergrain forces in low-Mach-number plasma wakes.
AB  - Large-scale particle-in-cell calculations of the plasma wake interactions of two
      negatively charged grains smaller than the Debye length are carried out using the
      coptic code over a wide range of subsonic plasma flow velocities. In plasmas with
      the temperature ratio T(e)/T(i)=100, it is found that a single grain's
      oscillatory wake disappears for flow Mach numbers M less than approximately 0.3,
      which is the parameter regime where Landau damping is expected to be strong.
      Neutral collisions suppress potential oscillations above M=0.3, but not the
      trailing attractive potential peak caused by ion focusing. The transverse (grain
      aligning) force on a downstream particle in the wake of another is obtained
      rigorously from the code in three-dimensional simulations. It shows general
      agreement with the force that would be deduced from the single-grain wake
      potential gradient. Except for relatively large grains in the nonlinear
      collisional regime, the grain-aligning force is very small for slow flow.

PMID- 23005231
TI  - Second-order nonlinear Schrodinger equation breather solutions in the degenerate
      and rogue wave limits.
AB  - We present an explicit analytic form for the two-breather solution of the
      nonlinear Schrodinger equation with imaginary eigenvalues. It describes various
      nonlinear combinations of Akhmediev breathers and Kuznetsov-Ma solitons. The
      degenerate case, when the two eigenvalues coincide, is quite involved. The
      standard inverse scattering technique does not generally provide an answer to
      this scenario. We show here that the solution can still be found as a special
      limit of the general second-order expression and appears as a mixture of
      polynomials with trigonometric and hyperbolic functions. A further restriction of
      this particular case, where the two eigenvalues are equal to i, produces the
      second-order rogue wave with two free parameters considered as differential
      shifts. The illustrations reveal a precarious dependence of wave profile on the
      degenerate eigenvalues and differential shifts. Thus we establish a hierarchy of
      second-order solutions, revealing the interrelated nature of the general case,
      the rogue wave, and the degenerate breathers.

PMID- 23005232
TI  - Simple waves in Hertzian chains.
AB  - The discrete system of equations for a chain consisting of a large number of
      spheres interacting via the Hertz force of index 3/2 in strain is examined in the
      very long wavelength limit, yielding an effective medium description. The
      resulting continuum second-order equation of motion possesses a subset of simple
      waves obeying a first-order equation of reduced index 5/4. These simple waves
      appear not to have examined before. For a given initial strain, the simple wave
      solution prescribes initial sphere centroid velocities. Together the initial
      strain and velocities are used in the second-order discrete system. Results for
      shock wave development compare very well between the second-order discrete system
      (minus physically valid oscillations) and the reduced first-order equation. A
      second-order simulation of colliding waves examines the ability of waves to pass
      through each other, with a phase advance accruing during the collision process.
      An arbitrary initial condition is shown to evolve toward a universal similarity
      solution proportional to (x/t)(4). A closed-form solution is given including the
      complete history of the waveform, shock location, and amplitude.

PMID- 23005233
TI  - Homogenization of Maxwell's equations in periodic composites: boundary effects
      and dispersion relations.
AB  - We consider the problem of homogenizing the Maxwell equations for periodic
      composites. The analysis is based on Bloch-Floquet theory. We calculate
      explicitly the reflection coefficient for a half space and derive and implement a
      computationally efficient continued-fraction expansion for the effective
      permittivity. Our results are illustrated by numerical computations for the case
      of two-dimensional systems. The homogenization theory of this paper is designed
      to predict various physically measurable quantities rather than to simply
      approximate certain coefficients in a partial differential equation.

PMID- 23005234
TI  - Nonlinear absorption due to linear loss and magnetic permeability in
      metamaterials.
AB  - We predict theoretically that linear magnetic permeability induces nonlinear
      absorption (NA) of an electric field in lossy metamaterials (MMs) with Kerr-type
      nonlinear polarization even when the imaginary part of the nonlinear polarization
      is absent. The nonlinear magnetic susceptibility, if it exists and although it
      may be real, enhances or reduces the NA of the electric field, depending on the
      relative values of the electric and magnetic losses. In particular, it is shown
      that the NA effect can be tuned by the figure of merit (FOM) of the MM:
      generally, MMs with a better FOM have a weaker NA effect. Moreover, the nonlinear
      coefficient can also be enhanced greatly due to the combined effect of the linear
      losses and the nonlinear magnetization of MMs. The control of the tunable NA and
      nonlinear coefficients by the structural parameters of MMs is also discussed.

PMID- 23005235
TI  - Elasticity of mechanical oscillators in nonequilibrium steady states:
      experimental, numerical, and theoretical results.
AB  - We study experimentally, numerically, and theoretically the elastic response of
      mechanical resonators along which the temperature is not uniform, as a
      consequence of the onset of steady-state thermal gradients. Two experimental
      setups and designs are employed, both using low-loss materials. In both cases, we
      monitor the resonance frequencies of specific modes of vibration, as they vary
      along with variations of temperatures and of temperature differences. In one
      case, we consider the first longitudinal mode of vibration of an aluminum alloy
      resonator; in the other case, we consider the antisymmetric torsion modes of a
      silicon resonator. By defining the average temperature as the volume-weighted
      mean of the temperatures of the respective elastic sections, we find out that the
      elastic response of an object depends solely on it, regardless of whether a
      thermal gradient exists and, up to 10% imbalance, regardless of its magnitude.
      The numerical model employs a chain of anharmonic oscillators, with first- and
      second-neighbor interactions and temperature profiles satisfying Fourier's Law to
      a good degree. Its analysis confirms, for the most part, the experimental
      findings and it is explained theoretically from a statistical mechanics
      perspective with a loose notion of local equilibrium.

PMID- 23005236
TI  - Mixed convolved action.
AB  - A stationary principle is developed for dynamical systems by formulating the
      concept of mixed convolved action, which is written in terms of displacement and
      force variables, using temporal convolutions and fractional derivatives. The
      classical canonical single-degree-of-freedom dynamical system is considered as an
      initial application. With this new formulation, a single real scalar functional
      provides the governing differential equations, along with all the pertinent
      initial conditions, as the Euler-Lagrange equations emanating from the
      stationarity of the mixed convolved action. Both conservative and non
      conservative processes can be considered within a common framework, thus
      resolving a long-standing limitation of variational approaches for dynamical
      systems. Several results in fractional calculus also are developed.

PMID- 23005237
TI  - Numerical convergence of the self-diffusion coefficient and viscosity obtained
      with Thomas-Fermi-Dirac molecular dynamics.
AB  - Computations of the self-diffusion coefficient and viscosity in warm dense matter
      are presented with an emphasis on obtaining numerical convergence and a careful
      evaluation of the standard deviation. The transport coefficients are computed
      with the Green-Kubo relation and orbital-free molecular dynamics at the Thomas
      Fermi-Dirac level. The numerical parameters are varied until the Green-Kubo
      integral is equal to a constant in the t->+infinity limit; the transport
      coefficients are deduced from this constant and not by extrapolation of the Green
      Kubo integral. The latter method, which gives rise to an unknown error, is tested
      for the computation of viscosity; it appears that it should be used with caution.
      In the large domain of coupling constant considered, both the self-diffusion
      coefficient and viscosity turn out to be well approximated by simple analytical
      laws using a single effective atomic number calculated in the average-atom model.

PMID- 23005238
TI  - Free-energy calculation via mean-force dynamics using a logarithmic energy
      landscape.
AB  - A method for free-energy calculation based on mean-force dynamics (fictitious
      dynamics on a potential of mean force) is presented. The method utilizes a
      logarithmic form of free energy to enhance crossing barriers on a free-energy
      landscape, which results in efficient sampling of "rare" events. Invoking a
      conserved quantity in mean-force dynamics, free energy can be estimated on-the
      fly without postprocessing. This means that an estimate of the free-energy
      profile can be locally made in contrast to the other methods based on mean-force
      dynamics such as metadynamics. The method is benchmarked against conventional
      methods and its high efficiency is demonstrated in the free-energy calculation
      for a glycine dipeptide molecule.

PMID- 23005239
TI  - Optimization of a Brownian-dynamics algorithm for semidilute polymer solutions.
AB  - Simulating the static and dynamic properties of semidilute polymer solutions with
      Brownian dynamics (BD) requires the computation of a large system of polymer
      chains coupled to one another through excluded-volume and hydrodynamic
      interactions. In the presence of periodic boundary conditions, long-ranged
      hydrodynamic interactions are frequently summed with the Ewald summation
      technique. By performing detailed simulations that shed light on the influence of
      several tuning parameters involved both in the Ewald summation method, and in the
      efficient treatment of Brownian forces, we develop a BD algorithm in which the
      computational cost scales as O(N(1.8)), where N is the number of monomers in the
      simulation box. We show that Beenakker's original implementation of the Ewald
      sum, which is only valid for systems without bead overlap, can be modified so
      that theta solutions can be simulated by switching off excluded-volume
      interactions. A comparison of the predictions of the radius of gyration, the end
      to-end vector, and the self-diffusion coefficient by BD, at a range of
      concentrations, with the hybrid lattice Boltzmann-molecular dynamics (LB-MD)
      method shows excellent agreement between the two methods. In contrast to the
      situation for dilute solutions, the LB-MD method is shown to be significantly
      more computationally efficient than the current implementation of BD for
      simulating semidilute solutions. We argue, however, that further optimizations
      should be possible.

PMID- 23005240
TI  - Direct numerical simulation of dispersed particles in a compressible fluid.
AB  - We present a direct numerical simulation method for investigating the dynamics of
      dispersed particles in a compressible solvent fluid. The validity of the
      simulation is examined by calculating the velocity relaxation of an impulsively
      forced spherical particle with a known analytical solution. The simulation also
      gives information about the fluid motion, which provides some insight into the
      particle motion. Fluctuations are also introduced by random stress, and the
      validity of this case is examined by comparing the calculation results with the
      fluctuation-dissipation theorem.

PMID- 23005241
TI  - Modified unified kinetic scheme for all flow regimes.
AB  - A modified unified kinetic scheme for the prediction of fluid flow behaviors in
      all flow regimes is described. The time evolution of macrovariables at the cell
      interface is calculated with the idea that both free transport and collision
      mechanisms should be considered. The time evolution of macrovariables is obtained
      through the conservation constraints. The time evolution of local Maxwellian
      distribution is obtained directly through the one-to-one mapping from the
      evolution of macrovariables. These improvements provide more physical realities
      in flow behaviors and more accurate numerical results in all flow regimes
      especially in the complex transition flow regime. In addition, the improvement
      steps introduce no extra computational complexity.

PMID- 23005242
TI  - Direct calculation of the lattice Green function with arbitrary interactions for
      general crystals.
AB  - Efficient computation of lattice defect geometries such as point defects,
      dislocations, disconnections, grain boundaries, interfaces, and free surfaces
      requires accurate coupling of displacements near the defect to the long-range
      elastic strain. Flexible boundary condition methods embed a defect in infinite
      harmonic bulk through the lattice Green function. We demonstrate an efficient and
      accurate calculation of the lattice Green function from the force-constant matrix
      for general crystals with an arbitrary basis by extending a method for Bravais
      lattices. New terms appear due to the presence of optical modes and the possible
      loss of inversion symmetry. By separately treating poles and discontinuities in
      reciprocal space, numerical accuracy is controlled at all distances. We compute
      the lattice Green function for a two-dimensional model with broken symmetry to
      elucidate the role of different coupling terms. The algorithm is generally
      applicable in two and three dimensions to crystals with arbitrary number of atoms
      in the unit cell, symmetry, and interactions.

PMID- 23005243
TI  - Generalized Metropolis dynamics with a generalized master equation: an approach
      for time-independent and time-dependent Monte Carlo simulations of generalized
      spin systems.
AB  - The extension of Boltzmann-Gibbs thermostatistics, proposed by Tsallis,
      introduces an additional parameter q to the inverse temperature beta. Here, we
      show that a previously introduced generalized Metropolis dynamics to evolve spin
      models is not local and does not obey the detailed energy balance. In this
      dynamics, locality is only retrieved for q=1, which corresponds to the standard
      Metropolis algorithm. Nonlocality implies very time-consuming computer
      calculations, since the energy of the whole system must be reevaluated when a
      single spin is flipped. To circumvent this costly calculation, we propose a
      generalized master equation, which gives rise to a local generalized Metropolis
      dynamics that obeys the detailed energy balance. To compare the different
      critical values obtained with other generalized dynamics, we perform Monte Carlo
      simulations in equilibrium for the Ising model. By using short-time
      nonequilibrium numerical simulations, we also calculate for this model the
      critical temperature and the static and dynamical critical exponents as functions
      of q. Even for q?1, we show that suitable time-evolving power laws can be found
      for each initial condition. Our numerical experiments corroborate the literature
      results when we use nonlocal dynamics, showing that short-time parameter
      determination works also in this case. However, the dynamics governed by the new
      master equation leads to different results for critical temperatures and also the
      critical exponents affecting universality classes. We further propose a simple
      algorithm to optimize modeling the time evolution with a power law, considering
      in a log-log plot two successive refinements.

PMID- 23005244
TI  - Discrete differential geometry: the nonplanar quadrilateral mesh.
AB  - We consider the problem of constructing a discrete differential geometry defined
      on nonplanar quadrilateral meshes. Physical models on discrete nonflat spaces are
      of inherent interest, as well as being used in applications such as computation
      for electromagnetism, fluid mechanics, and image analysis. However, the majority
      of analysis has focused on triangulated meshes. We consider two approaches:
      discretizing the tensor calculus, and a discrete mesh version of differential
      forms. While these two approaches are equivalent in the continuum, we show that
      this is not true in the discrete case. Nevertheless, we show that it is possible
      to construct mesh versions of the Levi-Civita connection (and hence the tensorial
      covariant derivative and the associated covariant exterior derivative), the
      torsion, and the curvature. We show how discrete analogs of the usual vector
      integral theorems are constructed in such a way that the appropriate conservation
      laws hold exactly on the mesh, rather than only as approximations to the
      continuum limit. We demonstrate the success of our method by constructing a mesh
      version of classical electromagnetism and discuss how our formalism could be used
      to deal with other physical models, such as fluids.

PMID- 23005245
TI  - Reconstruction of three-dimensional porous media using a single thin section.
AB  - The purpose of any reconstruction method is to generate realizations of two- or
      multiphase disordered media that honor limited data for them, with the hope that
      the realizations provide accurate predictions for those properties of the media
      for which there are no data available, or their measurement is difficult. An
      important example of such stochastic systems is porous media for which the
      reconstruction technique must accurately represent their morphology--the
      connectivity and geometry--as well as their flow and transport properties. Many
      of the current reconstruction methods are based on low-order statistical
      descriptors that fail to provide accurate information on the properties of
      heterogeneous porous media. On the other hand, due to the availability of high
      resolution two-dimensional (2D) images of thin sections of a porous medium, and
      at the same time, the high cost, computational difficulties, and even
      unavailability of complete 3D images, the problem of reconstructing porous media
      from 2D thin sections remains an outstanding unsolved problem. We present a
      method based on multiple-point statistics in which a single 2D thin section of a
      porous medium, represented by a digitized image, is used to reconstruct the 3D
      porous medium to which the thin section belongs. The method utilizes a 1D raster
      path for inspecting the digitized image, and combines it with a cross-correlation
      function, a grid splitting technique for deciding the resolution of the
      computational grid used in the reconstruction, and the Shannon entropy as a
      measure of the heterogeneity of the porous sample, in order to reconstruct the 3D
      medium. It also utilizes an adaptive technique for identifying the locations and
      optimal number of hard (quantitative) data points that one can use in the
      reconstruction process. The method is tested on high resolution images for Berea
      sandstone and a carbonate rock sample, and the results are compared with the
      data. To make the comparison quantitative, two sets of statistical tests
      consisting of the autocorrelation function, histogram matching of the local
      coordination numbers, the pore and throat size distributions, multiple-points
      connectivity, and single- and two-phase flow permeabilities are used. The
      comparison indicates that the proposed method reproduces the long-range
      connectivity of the porous media, with the computed properties being in good
      agreement with the data for both porous samples. The computational efficiency of
      the method is also demonstrated.

PMID- 23005246
TI  - Velocity-enhanced cooperation of moving agents playing public goods games.
AB  - In this paper we study the evolutionary dynamics of the public goods game in a
      population of mobile agents embedded in a two-dimensional space. In this
      framework, the backbone of interactions between agents changes in time, allowing
      us to study the impact that mobility has on the emergence of cooperation in
      structured populations. Our results point out that a low degree of mobility
      enhances cooperation in the system. In addition, we study the impact of the size
      of the groups in which games are played on cooperation. Again we find a rise and
      fall of cooperation related to the percolation point of the instant interaction
      networks created by the set of mobile agents.

PMID- 23005247
TI  - Addendum to "Two-fluid confined flow in a cylinder driven by a rotating endwall".
AB  - In a recent paper [Phys. Rev. E 85, 016308 (2012)], we reported on numerical
      simulations of swirling two-phase flows in which for cases where the viscosity of
      the upper fluid is sufficiently smaller than that of the lower fluid, a small
      region of reversed flow is present on the interface. In this Brief Report, we
      show that the reported reversed flow is grid converged and comment further on its
      physical origin.

PMID- 23005248
TI  - Acoustic vector solitons.
AB  - A theory of an acoustic vector soliton of self-induced transparency is
      constructed. By using the perturbative reduction method the magnetic Bloch
      equations and the equation of motion for the displacement field for the small
      area pulse are reduced to a system of two coupled nonlinear Schrodinger
      equations. The shape of an acoustic vector soliton with the sum and difference of
      the frequencies is presented. Explicit analytical expressions for the parameters
      of an acoustic vector soliton are obtained as well as simulations of an acoustic
      vector soliton presented with realistic parameters which can be reached in
      experiments. It is shown that the vector soliton in the special case can be
      reduced to the breather solution, and these nonlinear waves have different
      profiles.

PMID- 23005249
TI  - State-space-split method for some generalized Fokker-Planck-Kolmogorov equations
      in high dimensions.
AB  - The state-space-split method for solving the Fokker-Planck-Kolmogorov equations
      in high dimensions is extended to solving the generalized Fokker-Planck
      Kolmogorov equations in high dimensions for stochastic dynamical systems with a
      polynomial type of nonlinearity and excited by Poissonian white noise. The
      probabilistic solution of the motion of the stretched Euler-Bernoulli beam with
      cubic nonlinearity and excited by uniformly distributed Poissonian white noise is
      analyzed with the presented solution procedure. The numerical analysis shows that
      the results obtained with the state-space-split method together with the
      exponential polynomial closure method are close to those obtained with the Monte
      Carlo simulation when the relative value of the basic system relaxation time and
      the mean arrival time of the Poissonian impulse is in some limited range.

PMID- 23005250
TI  - Protein flexibility in virtual screening: the BACE-1 case study.
AB  - Simulating protein flexibility is a major issue in the docking-based drug-design
      process for which a single methodological solution does not exist. In our search
      of new anti-Alzheimer ligands, we were faced with the challenge of including
      receptor plasticity in a virtual screening campaign aimed at finding new beta
      secretase inhibitors. To this aim, we incorporated protein flexibility in our
      simulations by using an ensemble of static X-ray enzyme structures to screen the
      National Cancer Institute database. A unified description of the protein motion
      was also generated by computing and combining a set of grid maps using an energy
      weighting scheme. Such a description was used in an energy-weighted virtual
      screening experiment on the same molecular database. Assessment of the enrichment
      factors from these two virtual screening approaches demonstrated comparable
      predictive powers, with the energy-weighted method being faster than the ensemble
      method. The in vitro evaluation demonstrated that out of the 32 tested ligands,
      17 featured the predicted enzyme inhibiting property. Such an impressive success
      rate (53.1%) demonstrates the enhanced power of the two methodologies and
      suggests that energy-weighted virtual screening is a more than valid alternative
      to ensemble virtual screening given its reduced computational demands and
      comparable performance.

PMID- 23005251
TI  - The complete mitochondrial genome of the Bristletail Songmachilis xinxiangensis
      (Archaeognatha: Machilidae).
AB  - This study determined the complete mitochondrial genome of the bristletail
      Songmachilis xinxiangensis (Machilidae: Machilinae). It is a circular molecule of
      15,473 bp long, and contains 37 genes typically found in other insects, with 13
      protein-coding genes, 2 ribosomal RNA subunits genes, and 22 tRNA genes. The
      mitochondrial genome arrangement of S. xinxiangensis was similar to Pedetontus
      silvestrii (Machilidae: Petrobiinae) and Nesomachilis australica
      (Meinertellidae), but different from Trigoniophthalmus alternatus (Machilidae:
      Machilinae) in position of tRNA(Ala) and Petrobius brevistylis (Machilidae:
      Petrobiinae) in the position of tRNA(Tyr). The A+T content of total nucleotide
      and control region is 73.6% and 86%, respectively.

PMID- 23005253
TI  - The moderating role of dental expectancies on the relationship between cognitive
      vulnerability and dental fear in children and adolescents.
AB  - OBJECTIVE: Recently, cognitive approaches have been successfully applied to the
      understanding of child dental anxiety. Our study aimed to analyze the interplay
      between cognitive variables and their associations with dental fear. In
      particular, we proposed that the observed relationship between dental treatment
      related cognitive vulnerability (i.e., uncontrollability, unpredictability,
      dangerousness, and disgustingness appraisals) and dental fear is moderated by the
      expectancies of the probability and aversiveness of negative events during dental
      treatments. METHODS: A questionnaire survey was conducted with data obtained from
      179 participants (8-18 years, 55.9% female) who attended 12 randomly selected
      educational establishments in Madrid (Spain). RESULTS: Dental fear was associated
      with an irregular pattern of dental visits. As expected, cognitive vulnerability
      was strongly linked to dental anxiety. For those children who expected a lower
      likelihood of negative dental events or appraised them in a less aversive way,
      the relationship between cognitive vulnerability and fear was attenuated.
      CONCLUSIONS: As dental fear and oral health are connected, the prevention and
      reduction of dental fear among children and adolescents might be a worthwhile
      target for public health interventions. Our study sheds some light on how this
      could be achieved, that is, by modifying the children's vulnerability appraisals
      as well as their fearful dental expectancies.

PMID- 23005254
TI  - Pentoxifylline and cyclosporine in the treatment of febrile ulceronecrotic Mucha
      Habermann disease.
AB  - We describe two pediatric cases of febrile ulceronecrotic Mucha-Habermann disease
      (FUMHD) with response to pentoxifylline and cyclosporine therapies. Based on our
      review of the literature, we are presenting the first case of FUMHD treated with
      pentoxifylline and the third case of FUMHD successfully treated with
      cyclosporine. These agents may be of therapeutic benefit in the treatment of
      FUMHD, in part by suppressing tumor necrosis factor-alpha, which we believe may
      mediate the disease process. 

PMID- 23005255
TI  - Reactivity control in iron(III) amino triphenolate complexes: comparison of
      monomeric and dimeric complexes.
AB  - Iron(III) amino triphenolate complexes with different substituents in the ortho
      position of the phenolate moiety (R = H, Me, tBu, or Ph) have been synthesized by
      the reaction of iron(III) chloride and the sodium salt (Na(3)L(R)) of the
      requisite ligand. The complexes have been shown to be of either monomeric
      ([FeL(R)(THF)]) or dimeric ([FeL(R)](2)) nature by a combination of X-ray
      diffraction, (1)H NMR, solution magnetic susceptibility, and cyclic voltammetry
      studies. These analytical studies have shown that the monomeric and dimeric
      [FeL(R)] complexes behave distinctively, and that the dimer stability is a
      function of the ortho-positioned groups. Both the dimeric as well as monomeric
      complexes were tested as catalysts for the catalytic cycloaddition of carbon
      dioxide to oxiranes, and the data show that the monomeric complexes are able to
      mediate this conversion with significantly higher activities than the dimeric
      complexes. This difference in reactivity is controlled by the substitution
      pattern on the ligand L(R), and is in line with the catalytic requisite of
      binding of the epoxide substrate by the iron(III) center.

PMID- 23005256
TI  - Predictions for cholesterol interaction sites on the A2A adenosine receptor.
AB  - Molecular dynamics simulations of the A(2A) adenosine receptor totaling 1.4 MUs
      show clear evidence for specific sites mediating interactions between adenosine
      bound A(2A) and cholesterol. The strongest evidence is for three binding sites.
      Two are in the extracellular leaflet, with one site interacting with helices VII
      and I, and the other with helices II and III. One site is located in the
      intracellular leaflet, interacting with helices III and IV. One of our three
      predicted binding sites is confirmed by a just-published high-resolution
      structure of A(2A) cocrystallized with an antagonist.

PMID- 23005257
TI  - Obesity lowers the threshold of allergic sensitization and augments airway
      eosinophilia in a mouse model of asthma.
AB  - BACKGROUND: Clinical and epidemiological studies show a close association between
      obesity and the risk of asthma development. The underlying cause-effect
      relationship between metabolism, innate and adaptive immunity, and inflammation
      remains to be elucidated. METHODS: We developed an animal model to study the
      interaction between metabolic abnormalities and experimentally induced asthma.
      Obesity-susceptible AKR mice were fed with high-fat diet (HFD) or normal low-fat
      diet (LFD) and subjected to a protocol of ovalbumin (OVA) sensitization and
      airway allergen challenges followed by assessment of inflammation and lung
      function. RESULTS: AKR mice developed obesity and a prestage of metabolic
      syndrome following HFD. This phenotype was associated with an increase in
      proinflammatory macrophages (CD11b+/CD11c+) together with higher serum levels of
      interleukin 6. Obese mice showed increased susceptibility to allergic
      sensitization as compared to LFD animals. Anti-ovalbumin IgE antibody titers
      correlated positively and anti-OVA IgG2a antibodies titers correlated negatively
      with body weight. Airway eosinophilia showed a positive correlation with body
      weight, whereas mucus production did not change with obesity. CONCLUSIONS: This
      obesity model demonstrates that HFD-induced obesity lowers the sensitization
      threshold in a model of asthma. This finding helps to understand why,
      particularly during childhood, obesity is a risk factor for the development of
      allergic asthma.

PMID- 23005258
TI  - Examining discriminant validity issues of the Sport Motivation Scale-6.
AB  - The current study was conducted to re-assess the factor structure of the 24-item
      Sport Motivation Scale-6 (SMS-6; Mallett, Kawabata, Newcombe, Otero-Forero, &
      Jackson, 2007) with an independent sample. A total of 437 participants completed
      the SMS-6, and their responses were examined with confirmatory factor analysis
      and recent exploratory structural equation modelling (Asparouhov & Muthen, 2009).
      A six-factor confirmatory-factor-analysis model did not fit to the sample data
      adequately. Through examination of the corresponding exploratory-structural
      equation-modelling solution, it was found that two items loaded on non-target
      factors poorly. This result was replicated by a published data set (Mallett,
      Kawabata, Newcombe, et al., 2007). The modified confirmatory-factor-analysis
      model with these two items removed fit to the present study's data satisfactorily
      and all six factors were adequately diferentiated. These results generally
      validate the SMS-6 responses. Furthermore, this study demonstrated the usefulness
      of a comparison of confirmatory-factor-analysis and exploratory-structural
      equation-modelling solutions for an accurate interpretation of individual
      parameters.

PMID- 23005259
TI  - Long sleep duration and cause-specific mortality according to physical function
      and self-rated health: the Ohsaki Cohort Study.
AB  - Although several studies have examined the association between sleep duration and
      all-cause or cause-specific mortality, it is unclear whether long sleep duration
      might merely reflect decreased physical strength and poorer health status. We
      therefore examined the association between sleep duration and all-cause and cause
      specific mortality, and conducted stratified analysis based on physical function
      and self-rated health. This study used prospective data from the Ohsaki Cohort
      Study, conducted in Miyagi Prefecture, in northern Japan. This study population
      comprised 49 256 subjects aged 40-79 years at the baseline survey. We estimated
      hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cause
      specific mortality according to the five categories of sleep duration (<=6, 7, 8,
      9, >=10 h day(-1) ), treating 7 h as the reference group, employing Cox's
      proportional hazard regression analysis. We found that long sleep duration was
      associated with mortality. The HRs (95% CIs) of subjects who slept more than 10 h
      were 1.37 (1.27-1.47), 1.49 (1.30-1.71) and 1.53 (1.36-1.73) for mortality due to
      all causes, total cardiovascular disease and other causes of death mortality,
      respectively. The association between long sleep duration and stroke mortality
      was especially marked among subjects with limited physical function and poorer
      health status. However, we did not observe such a trend for mortality due to all
      causes, total cardiovascular disease, ischaemic heart disease, cancer or other
      causes of death. We conclude that, with the exception of stroke mortality, the
      association between long sleep duration and mortality is not modified by physical
      function or health status.

PMID- 23005261
TI  - Retraction.
AB  - Optical properties of substituted piperidine containing natural quinolizidine
      alkaloids--theoretical versus experimental study. Bojidarka Ivanova and Michael
      Spiteller, Natural Product Research, DOI: 10.1080/14786419.2012.676546 (2012).
      This article has been retracted at the request of the Publisher in consultation
      with the Editor due to concerns and issues relating to the authorship of the
      article.

PMID- 23005262
TI  - Retraction.
AB  - Substituted Iboga-alkaloids and their model receptor interactions--theoretical
      and experimental studies. Bojidarka Ivanova and Michael Spiteller, Natural
      Product Research, DOI: 10.1080/14786419.2012.704375 (2012). This article has been
      retracted at the request of the Publisher in consultation with the Editor due to
      concerns and issues relating to the authorship of the article.

PMID- 23005264
TI  - Bivariate marker measurements and ROC analysis.
AB  - This article considers receiver operating characteristic (ROC) analysis for
      bivariate marker measurements. The research interest is to extend tools and rules
      from univariate marker to bivariate marker setting for evaluating predictive
      accuracy of markers using a tree-based classification rule. Using an and-or
      classifier, an ROC function together with a weighted ROC function (WROC) and
      their conjugate counterparts are proposed for examining the performance of
      bivariate markers. The proposed functions evaluate the performance of and-or
      classifiers among all possible combinations of marker values, and are ideal
      measures for understanding the predictability of biomarkers in target population.
      Specific features of ROC and WROC functions and other related statistics are
      discussed in comparison with those familiar properties for univariate marker.
      Nonparametric methods are developed for estimating ROC-related functions
      (partial) area under curve and concordance probability. With emphasis on average
      performance of markers, the proposed procedures and inferential results are
      useful for evaluating marker predictability based on a single or bivariate marker
      (or test) measurements with different choices of markers, and for evaluating
      different and-or combinations in classifiers. The inferential results developed
      in this article also extend to multivariate markers with a sequence of
      arbitrarily combined and-or classifier.

PMID- 23005265
TI  - Classical simulation of entanglement swapping with bounded communication.
AB  - Entanglement appears under two different forms in quantum theory, namely, as a
      property of states of joint systems and as a property of measurement eigenstates
      in joint measurements. By combining these two aspects of entanglement, it is
      possible to generate nonlocality between particles that never interacted, using
      the protocol of entanglement swapping. We show that even in the more constraining
      bilocal scenario where distant sources of particles are assumed to be
      independent, i.e., to share no prior randomness, entanglement swapping can be
      simulated classically with bounded communication, using only 9 bits in total. Our
      result thus provides an upper bound on the nonlocality of the entanglement
      swapping process.

PMID- 23005263
TI  - Effects of rho-Da1a a peptidic alpha(1) (A) -adrenoceptor antagonist in human
      isolated prostatic adenoma and anaesthetized rats.
AB  - BACKGROUND AND PURPOSE: rho-Da1a, a 65 amino-acid peptide, has subnanomolar
      affinity and high selectivity for the human alpha(1) (A) -adrenoceptor subtype.
      The purpose of this study was to characterize the pharmacological effects of rho
      Da1a on prostatic function, both in vivo and in vitro. EXPERIMENTAL APPROACH: rho
      Da1a was tested as an antagonist of adrenaline-induced effects on COS cells
      transfected with the human alpha(1) (A) -adrenoceptor as well as on human
      isolated prostatic adenoma obtained from patients suffering from benign prostatic
      hyperplasia. Moreover, we compared the effects of rho-Da1a and tamsulosin on
      phenylephrine (PHE)-induced increases in intra-urethral (IUP) and arterial
      pressures (AP) in anaesthetized rats, following i.v. or p.o. administration. KEY
      RESULTS: On COS cells expressing human alpha(1) (A) -adrenoceptors and on human
      prostatic strips, rho-Da1a inhibited adrenaline- and noradrenaline-induced
      effects. In anaesthetized rats, rho-Da1a and tamsulosin administered i.v. 30 min
      before PHE significantly antagonized the effects of PHE on IUP. The pK(B)  values
      for tamsulosin and rho-Da1a for this effect were similar. With regards to AP, rho
      Da1a only reduced the effect of PHE on AP at the lowest dose tested (10 MUg.kg(
      1) ), whereas tamsulosin significantly reduced PHE effects at doses between 10
      and 150 MUg.kg(-1) . CONCLUSIONS AND IMPLICATIONS: rho-Da1a exhibited a relevant
      effect on IUP and a small effect on AP. In contrast, tamsulosin antagonized the
      effects of PHE on both IUP and AP. We conclude that rho-Da1a is more uroselective
      than tamsulosin. rho-Da1a is the most selective peptidic antagonist for alpha(1A)
      -adenoceptors identified to date and could be a new treatment for various
      urological diseases.

PMID- 23005266
TI  - Intensity-dependent electron mass shift in a laser field: existence,
      universality, and detection.
AB  - The electron mass shift in a laser field has long remained an elusive concept. We
      show that the mass shift can exist in pulses but that it is neither unique nor
      universal: it can be reduced by pulse shaping. We show also that the detection of
      mass shift effects in laser-particle scattering experiments is feasible with
      current technology, even allowing for the transverse structure of realistic
      beams.

PMID- 23005267
TI  - Multiple Schrodinger pictures and dynamics in shortcuts to adiabaticity.
AB  - A Schrodinger equation may be unitarily transformed into dynamical equations in
      different interaction pictures which describe a common physical process, i.e.,
      the same underlying interactions and dynamics. In contrast to this standard
      scenario, other relations are also possible, such as a common interaction-picture
      dynamical equation corresponding to several Schrodinger equations that represent
      different physical processes. This may enable us to design alternative and
      feasible experimental routes for operations that are a priori difficult or
      impossible to perform. The power of this concept is exemplified by engineering
      Hamiltonians that improve the performance or make realizable several shortcuts to
      adiabaticity.

PMID- 23005268
TI  - Violation of Heisenberg's measurement-disturbance relationship by weak
      measurements.
AB  - While there is a rigorously proven relationship about uncertainties intrinsic to
      any quantum system, often referred to as "Heisenberg's uncertainty principle,"
      Heisenberg originally formulated his ideas in terms of a relationship between the
      precision of a measurement and the disturbance it must create. Although this
      latter relationship is not rigorously proven, it is commonly believed (and
      taught) as an aspect of the broader uncertainty principle. Here, we
      experimentally observe a violation of Heisenberg's "measurement-disturbance
      relationship", using weak measurements to characterize a quantum system before
      and after it interacts with a measurement apparatus. Our experiment implements a
      2010 proposal of Lund and Wiseman to confirm a revised measurement-disturbance
      relationship derived by Ozawa in 2003. Its results have broad implications for
      the foundations of quantum mechanics and for practical issues in quantum
      measurement.

PMID- 23005269
TI  - Quantum splines.
AB  - A quantum spline is a smooth curve parametrized by time in the space of unitary
      transformations, whose associated orbit on the space of pure states traverses a
      designated set of quantum states at designated times, such that the trace norm of
      the time rate of change of the associated Hamiltonian is minimized. The solution
      to the quantum spline problem is obtained, and is applied in an example that
      illustrates quantum control of coherent states. An efficient numerical scheme for
      computing quantum splines is discussed and implemented in the examples.

PMID- 23005270
TI  - Continuous variable quantum key distribution: finite-key analysis of composable
      security against coherent attacks.
AB  - We provide a security analysis for continuous variable quantum key distribution
      protocols based on the transmission of two-mode squeezed vacuum states measured
      via homodyne detection. We employ a version of the entropic uncertainty relation
      for smooth entropies to give a lower bound on the number of secret bits which can
      be extracted from a finite number of runs of the protocol. This bound is valid
      under general coherent attacks, and gives rise to keys which are composably
      secure. For comparison, we also give a lower bound valid under the assumption of
      collective attacks. For both scenarios, we find positive key rates using
      experimental parameters reachable today.

PMID- 23005271
TI  - Experimental implementation of encoded logical qubit operations in a perfect
      quantum error correcting code.
AB  - Large-scale universal quantum computing requires the implementation of quantum
      error correction (QEC). While the implementation of QEC has already been
      demonstrated for quantum memories, reliable quantum computing requires also the
      application of nontrivial logical gate operations to the encoded qubits. Here, we
      present examples of such operations by implementing, in addition to the identity
      operation, the NOT and the Hadamard gate to a logical qubit encoded in a five
      qubit system that allows correction of arbitrary single-qubit errors. We perform
      quantum process tomography of the encoded gate operations, demonstrate the
      successful correction of all possible single-qubit errors, and measure the
      fidelity of the encoded logical gate operations.

PMID- 23005272
TI  - Bayesian estimation of free energies from equilibrium simulations.
AB  - Free energy calculations are an important tool in statistical physics and
      biomolecular simulation. This Letter outlines a Bayesian method to estimate free
      energies from equilibrium Monte Carlo simulations. A Gibbs sampler is developed
      that allows efficient sampling of free energies and the density of states. The
      Gibbs sampling output can be used to estimate expected free energy differences
      and their uncertainties. The probabilistic formulation offers a unifying
      framework for existing methods such as the weighted histogram analysis method and
      the multistate Bennett acceptance ratio; both are shown to be approximate
      versions of the full probabilistic treatment.

PMID- 23005273
TI  - Multistability with a metastable mixed state.
AB  - Complex dynamical systems often show multiple metastable states. In
      macroevolution, such behavior is suggested by punctuated equilibrium and discrete
      geological epochs. In molecular biology, bistability is found in epigenetics and
      in the many mutually exclusive states that a human cell can take. Sociopolitical
      systems can be single-party regimes or a pluralism of balancing political
      fractions. To introduce multistability, we suggest a model system of D mutually
      exclusive microstates that battle for dominance in a large system. Assuming one
      common intermediate state, we obtain D+1 metastable macrostates for the system,
      one of which is a self-reinforced mixture of all D+1 microstates. Robustness of
      this metastable mixed state increases with diversity D.

PMID- 23005274
TI  - Chiral particle separation by a nonchiral microlattice.
AB  - We conceived a model experiment for a continuous separation strategy of chiral
      molecules (enantiomers) without the need of any chiral selector structure or
      derivatization agents: Microparticles that only differ by their chirality are
      shown to migrate along different directions when driven by a steady fluid flow
      through a square lattice of cylindrical posts. In accordance with our numerical
      predictions, the transport directions of the enantiomers depend very sensitively
      on the orientation of the lattice relative to the fluid flow.

PMID- 23005275
TI  - Efficient first-principles calculation of the quantum kinetic energy and momentum
      distribution of nuclei.
AB  - Light nuclei at room temperature and below exhibit a kinetic energy which
      significantly deviates from the predictions of classical statistical mechanics.
      This quantum kinetic energy is responsible for a wide variety of isotope effects
      of interest in fields ranging from chemistry to climatology. It also furnishes
      the second moment of the nuclear momentum distribution, which contains subtle
      information about the chemical environment and has recently become accessible to
      deep inelastic neutron scattering experiments. Here, we show how, by combining
      imaginary time path integral dynamics with a carefully designed generalized
      Langevin equation, it is possible to dramatically reduce the expense of computing
      the quantum kinetic energy. We also introduce a transient anisotropic Gaussian
      approximation to the nuclear momentum distribution which can be calculated with
      negligible additional effort. As an example, we evaluate the structural
      properties, the quantum kinetic energy, and the nuclear momentum distribution for
      a first-principles simulation of liquid water.

PMID- 23005276
TI  - Seismic probes of solar interior magnetic structure.
AB  - Sun spots are prominent manifestations of solar magnetoconvection, and imaging
      their subsurface structure is an outstanding problem of wide physical importance.
      Travel times of seismic waves that propagate through these structures are
      typically used as inputs to inversions. Despite the presence of strongly
      anisotropic magnetic waveguides, these measurements have always been interpreted
      in terms of changes to isotropic wave speeds and flow-advection-related Doppler
      shifts. Here, we employ partial-differential-equation-constrained optimization to
      determine the appropriate parametrization of the structural properties of the
      magnetic interior. Seven different wave speeds fully characterize helioseismic
      wave propagation: the isotropic sound speed, a Doppler-shifting flow-advection
      velocity, and an anisotropic magnetic velocity. The structure of magnetic media
      is sensed by magnetoacoustic slow and fast modes and Alfven waves, each of which
      propagates at a different wave speed. We show that even in the case of weak
      magnetic fields, significant errors may be incurred if these anisotropies are not
      accounted for in inversions. Translation invariance is demonstrably lost. These
      developments render plausible the accurate seismic imaging of magnetoconvection
      in the Sun.

PMID- 23005277
TI  - Towards hydrodynamics without an entropy current.
AB  - We present a generating functional which describes the equilibrium thermodynamic
      response of a relativistic system to external sources. A variational principle
      gives rise to constraints on the response parameters of relativistic
      hydrodynamics without making use of an entropy current. Our method reproduces and
      extends results available in the literature. It also provides a technique for
      efficiently computing n-point zero-frequency correlation functions within the
      hydrodynamic derivative expansion without the need to explicitly solve the
      equations of hydrodynamics.

PMID- 23005278
TI  - Measuring Higgs couplings from LHC data.
AB  - Following recent ATLAS and CMS publications we interpret the results of their
      Higgs searches in terms of standard model operators. For a Higgs boson mass of
      125 GeV we determine several Higgs couplings from published 2011 data and
      extrapolate the results towards different scenarios of LHC running. Even though
      our analysis is limited by low statistics we already derive meaningful
      constraints on modified Higgs sectors.

PMID- 23005281
TI  - Threshold region for Higgs boson production in gluon fusion.
AB  - We provide a quantitative determination of the effective partonic kinematics for
      Higgs boson production in gluon fusion in terms of the collider energy at the
      LHC. We use the result to assess, as a function of the Higgs boson mass, whether
      the large m(t) approximation is adequate and Sudakov resummation advantageous. We
      argue that our results hold to all perturbative orders. Based on our results, we
      conclude that the full inclusion of finite top mass corrections is likely to be
      important for accurate phenomenology for a light Higgs boson with m(H)~125 GeV at
      the LHC with ?s=14 TeV.

PMID- 23005280
TI  - Well-established nucleon resonances revisited by double-polarization
      measurements.
AB  - The first measurement is reported of the double-polarization observable G in the
      photoproduction of neutral pions off protons, covering the photon energy range
      from 620 to 1120 MeV and the full solid angle. G describes the correlation
      between the photon polarization plane and the scattering plane for protons
      polarized along the direction of the incoming photon. The observable is highly
      sensitive to contributions from baryon resonances. The new results are compared
      to the predictions from SAID, MAID, and BnGa partial wave analyses. In spite of
      the long-lasting efforts to understand gammap->ppi(0) as the simplest
      photoproduction reaction, surprisingly large differences between the new data and
      the latest predictions are observed which are traced to different contributions
      of the N(1535) resonance with spin parity J(P)=1/2(-) and N(1520) with J(P)=3/2(
      ). In the third resonance region, where N(1680) with J(P)=5/2(+) production
      dominates, the new data are reasonably close to the predictions.

PMID- 23005282
TI  - Lambda-to-kaon ratio enhancement in heavy ion collisions at several TeV.
AB  - We introduced recently a new theoretical scheme which accounts for
      hydrodynamically expanding bulk matter, jets, and the interaction between the
      two. Important for the particle production at intermediate values of transverse
      momentum (p(t)) are jet hadrons produced inside the fluid. They pick up quarks
      and antiquarks (or diquarks) from the thermal matter rather than creating them
      via the Schwinger mechanism-the usual mechanism of hadron production from string
      fragmentation. These hadrons carry plasma properties (flavor, flow) but also the
      large momentum of the transversely moving string segment connecting quark and
      antiquark (or diquark). They therefore show up at quite large values of p(t), not
      polluted by soft particle production. We will show that this mechanism leads to a
      pronounced peak in the Lambda-to-kaon ratio at intermediate p(t). The effect
      increases substantially with centrality, which reflects the increasing transverse
      size with centrality.

PMID- 23005283
TI  - Mass measurements of the neutron-deficient 41Ti, 45Cr, 49Fe, and 53Ni nuclides:
      first test of the isobaric multiplet mass equation in f p-shell nuclei.
AB  - Isochronous mass spectrometry has been applied to neutron-deficient 58Ni
      projectile fragments at the HIRFL-CSR facility in Lanzhou, China. Masses of a
      series of short-lived T(z)=-3/2 nuclides including 41Ti, 45Cr, 49Fe, and 53Ni
      have been measured with a precision of 20-40 keV. The new data enable us to test
      for the first time the isobaric multiplet mass equation (IMME) in fp-shell
      nuclei. We observe that the IMME is inconsistent with the generally accepted
      quadratic form for the A=53, T=3/2 quartet. We perform full space shell model
      calculations and compare them with the new experimental results.

PMID- 23005284
TI  - 100-fold reduction of electric-field noise in an ion trap cleaned with in situ
      argon-ion-beam bombardment.
AB  - Motional heating of trapped atomic ions is a major obstacle to their use as
      quantum bits in a scalable quantum computer. The detailed physical origin of this
      heating is not well understood, but experimental evidence suggests that it is
      caused by electric-field noise emanating from the surface of the trap electrodes.
      In this study, we have investigated the role of adsorbates on the electrodes by
      identifying contaminant overlayers, implementing an in situ argon-ion-beam
      cleaning treatment, and measuring ion heating rates before and after treating the
      trap electrodes' surfaces. We find a 100-fold reduction in heating rate after
      treatment. The experiments described here are sensitive to low levels of electric
      field noise in the MHz frequency range. Therefore, this approach could become a
      useful tool in surface science that complements established techniques.

PMID- 23005285
TI  - Anisotropy-induced Feshbach resonances in a quantum dipolar gas of highly
      magnetic atoms.
AB  - We explore the anisotropic nature of Feshbach resonances in the collision between
      ultracold highly magnetic submerged-shell dysprosium atoms in their energetically
      lowest magnetic sublevel, which can only occur due to couplings to rotating bound
      states. This is in contrast to well-studied alkali-metal atom collisions, where
      broadest (strongest) Feshbach resonances are hyperfine induced and due to
      rotationless bound states. Our first-principle coupled-channel calculation of the
      collisions between these spin-polarized bosonic dysprosium atoms reveals a strong
      interplay between the anisotropies in the dispersion and magnetic dipole-dipole
      interaction. The former anisotropy is absent in alkali-metal and chromium
      collisions. We show that both types of anisotropy significantly affect the
      Feshbach spectrum as a function of an external magnetic field. Effects of the
      electrostatic quadrupole-quadrupole interaction are small. Over a 20 mT magnetic
      field range, we predict about 10 Feshbach resonances and show that the resonance
      locations depend on the dysprosium isotope.

PMID- 23005286
TI  - Why three-body physics does not solve the proton-radius puzzle.
AB  - The possible involvement of weakly bound three-body systems in the muonic
      hydrogen spectroscopy experiment, which could resolve the current discrepancy
      between determinations of the proton radius, is investigated. Using variational
      calculations with complex coordinate rotation, we show that in the pMUe ion,
      which was recently proposed as a possible candidate, the pMU core fails to bind
      the outer electron tightly enough to explain the discrepancy. It is also shown
      that the ppMU molecular ion cannot play any role in the observed line.

PMID- 23005287
TI  - Reversal of photon-scattering errors in atomic qubits.
AB  - Spontaneous photon scattering by an atomic qubit is a notable example of
      environment-induced error and is a fundamental limit to the fidelity of quantum
      operations. In the scattering process, the qubit loses its distinctive and
      coherent character owing to its entanglement with the photon. Using a single
      trapped ion, we show that by utilizing the information carried by the photon, we
      are able to coherently reverse this process and correct for the scattering error.
      We further used quantum process tomography to characterize the photon-scattering
      error and its correction scheme and demonstrate a correction fidelity greater
      than 85% whenever a photon was measured.

PMID- 23005279
TI  - Evidence for an excess of B->D*tau(-)nu(tau) decays.
AB  - Based on the full BABAR data sample, we report improved measurements of the
      ratios R(D(*))=B(B[over -]->D(*)tau(-)nu[over -](tau))/B(B[over -]->D(*)l(l)(
      )nu[over -](l)), where l is either e or MU. These ratios are sensitive to new
      physics contributions in the form of a charged Higgs boson. We measure
      R(D)=0.440+/-0.058+/-0.042 and R(D(*))=0.332+/-0.024+/-0.018, which exceed the
      standard model expectations by 2.0sigma and 2.7sigma, respectively. Taken
      together, our results disagree with these expectations at the 3.4sigma level.
      This excess cannot be explained by a charged Higgs boson in the type II two-Higgs
      doublet model.

PMID- 23005288
TI  - Sub-Rayleigh lithography using high flux loss-resistant entangled states of
      light.
AB  - Quantum lithography achieves phase superresolution using fragile, experimentally
      challenging entangled states of light. We propose a scalable scheme for creating
      features narrower than classically achievable with reduced use of quantum
      resources and, consequently, enhanced resistance to loss. The scheme is an
      implementation of interferometric lithography using a mixture of a spontaneous
      parametric down-converted entangled state with intense classical coherent light.
      We measure coincidences of up to four photons mimicking multiphoton absorption.
      The results show a narrowing of the interference fringes of up to 30% with
      respect to the best analogous classical scheme using only 10% of the nonclassical
      light required for creating NOON states.

PMID- 23005289
TI  - Subkelvin parametric feedback cooling of a laser-trapped nanoparticle.
AB  - We optically trap a single nanoparticle in high vacuum and cool its three spatial
      degrees of freedom by means of active parametric feedback. Using a single laser
      beam for both trapping and cooling we demonstrate a temperature compression ratio
      of four orders of magnitude. The absence of a clamping mechanism provides robust
      decoupling from the heat bath and eliminates the requirement of cryogenic
      precooling. The small size and mass of the nanoparticle yield high resonance
      frequencies and high quality factors along with low recoil heating, which are
      essential conditions for ground state cooling and for low decoherence. The
      trapping and cooling scheme presented here opens new routes for testing quantum
      mechanics with mesoscopic objects and for ultrasensitive metrology and sensing.

PMID- 23005290
TI  - Generalized exact dynamic localization in curved coupled optical waveguide
      arrays.
AB  - We observed exact dynamic localization in its general case in strongly coupled
      curved waveguide arrays with periodic, nonsquare-wave curvatures. We achieved a
      six times change in the dynamic localization bandwidth by changing a design
      parameter in our deviated-square-wave curvature. By analyzing the relation
      between the bandwidth and curvature profile, we offer a general method to control
      the localization bandwidth.

PMID- 23005291
TI  - Origin of the pinning of drifting monostable patterns.
AB  - Under drift forces, a monostable pattern propagates. However, examples of
      nonpropagative dynamics have been observed. We show that the origin of this
      pinning effect comes from the coupling between the slow scale of the envelope to
      the fast scale of the modulation of the underlying pattern. We evidence that this
      effect stems from spatial inhomogeneities in the system. Experiments and numerics
      on drifting pattern-forming systems subjected to inhomogeneous spatial pumping or
      boundary conditions confirm this origin of pinning dynamics.

PMID- 23005292
TI  - Hyperbolic metamaterials as an analog of a blackbody in the near field.
AB  - We study the near-field heat exchange between hyperbolic materials and
      demonstrate that these media are able to support broadband frustrated modes which
      transport heat by photon tunneling with a high efficiency close to the
      theoretical limit. We predict that hyperbolic materials can be designed to be
      perfect thermal emitters at nanoscale and derive an upper limit for the heat flux
      due to hyperbolic modes.

PMID- 23005293
TI  - Relevance of uncorrelated Lorentzian pulses for the interpretation of turbulence
      in the edge of magnetically confined toroidal plasmas.
AB  - Recently, it has been proposed that the turbulent fluctuations measured in a
      linear plasma device could be described as a superposition of uncorrelated
      Lorentzian pulses with a narrow distribution of durations, which would provide an
      explanation for the reported quasiexponential power spectra. Here, we study the
      applicability of this proposal to edge fluctuations in toroidal magnetic
      confinement fusion plasmas. For the purpose of this analysis, we introduce a
      novel wavelet-based pulse-detection technique that offers important advantages
      over existing techniques. This technique allows for extracting the properties of
      individual pulses from the experimental time series, and for quantifying the
      distribution of pulse duration and energy as well as temporal correlations. We
      apply the wavelet technique to edge turbulent fluctuation data from the W7-AS
      stellarator and the JET tokamak, and find that the pulses detected in the data do
      not have a narrow distribution of durations and are not uncorrelated. Instead,
      the distributions are of the power-law type, exhibiting temporal correlations
      over scales much longer than the typical pulse duration. These results suggest
      that turbulence in open and closed field line systems may be distinct, and cast
      doubts on the proposed ubiquity of exponential power spectra in this context.

PMID- 23005294
TI  - Condensation dynamics in a quantum-quenched Bose gas.
AB  - By quenching the strength of interactions in a partially condensed Bose gas, we
      create a "supersaturated" vapor which has more thermal atoms than it can contain
      in equilibrium. Subsequently, the number of condensed atoms (N(0)) grows even
      though the temperature (T) rises and the total atom number decays. We show that
      the nonequilibrium evolution of the system is isoenergetic and, for small initial
      N(0), observe a clear separation between T and N(0) dynamics, thus explicitly
      demonstrating the theoretically expected "two-step" picture of condensate growth.
      For increasing initial N(0) values, we observe a crossover to classical
      relaxation dynamics. The size of the observed quench-induced effects can be
      explained using a simple equation of state for an interacting harmonically
      trapped atomic gas.

PMID- 23005295
TI  - Searching for Majorana fermions in 2D spin-orbit coupled Fermi superfluids at
      finite temperature.
AB  - Recent experimental breakthroughs in realizing spin-orbit (SO) coupling for cold
      atoms have spurred considerable interest in the physics of two-dimensional SO
      coupled Fermi superfluids, especially topological Majorana fermions (MFs) which
      were predicted to exist at zero temperature. However, it is well known that long
      range superfluid order is destroyed in two dimensions by phase fluctuations at
      finite temperature, and the relevant physics is the BKTs transition. In this
      Letter, we examine finite temperature effects on SO coupled Fermi gases and show
      that finite temperature is indeed necessary for the observation of MFs. Majorana
      fermions are topologically protected by a quasiparticle energy gap which is found
      to be much larger than the temperature. The restrictions to the parameter region
      for the observation of MFs have been obtained.

PMID- 23005296
TI  - Emergence of Majorana and Dirac particles in ultracold fermions via tunable
      interactions, spin-orbit effects, and Zeeman fields.
AB  - We discuss the emergence of rings of zero-energy excitations in momentum space
      for superfluid phases of ultracold fermions when spin-orbit effects, Zeeman
      fields, and interactions are varied. We show that phases containing rings of
      nodes possess nontrivial topological invariants, and that phase transitions
      between distinct topological phases belong to the Lifshitz class. Upon crossing
      phase boundaries, existing massless Dirac fermions in the gapless phase
      annihilate to produce bulk zero-mode Majorana fermions at phase boundaries, and
      then become massive Dirac fermions in the gapped phase. We characterize these
      tunable topological phase transitions via several spectroscopic properties,
      including excitation spectrum, spectral function, and momentum distribution.

PMID- 23005297
TI  - Ultrathin carbon nanotube with single, double, and triple bonds.
AB  - A metastable carbon nanotube with single, double, and triple bonds has been
      predicted from ab initio simulation. It results from the relaxation of an ideal
      carbon nanotube with chirality (2,1), without any potential barrier between the
      ideal nanotube and the new structure. Ten-membered carbon rings are formed by
      breaking carbon bonds between adjacent hexagons; eight-membered rings, already
      present in the ideal structure, become the smallest rings. This structure is
      stable in molecular dynamics simulations at temperatures up to 1000 K. Raman,
      infrared, and optical absorption spectra are simulated to allow its
      identification in the laboratory. The structure can be described as a double
      helical chain with alternating single, double, and triple bonds, where the chains
      are bridged by single bonds.

PMID- 23005298
TI  - Atomic-scale mechanisms of the glass-forming ability in metallic glasses.
AB  - The issue, composition dependence of glass-forming ability (GFA) in metallic
      glasses (MG), has been investigated by systematic experimental measurements
      coupled with theoretical calculations in Cu-Zr and Ni-Nb alloy systems. It is
      found that the atomic-level packing efficiency strongly relates to their GFA. The
      best GFA is located at the largest difference in the packing efficiency of the
      solute-centered clusters between the glassy and crystal alloys in both MG
      systems. This work provides an understanding of GFA from atomic level and will
      shed light on the development of new MGs with larger critical sizes.

PMID- 23005299
TI  - Confinement of anomalous liquids in nanoporous matrices.
AB  - Using molecular dynamics simulations, we investigate the effects of different
      nanoconfinements on complex liquids-e.g., colloids or protein solutions-with
      density anomalies and a liquid-liquid phase transition (LLPT). In all the
      confinements, we find a strong depletion effect with a large increase in liquid
      density near the confining surface. If the nanoconfinement is modeled by an
      ordered matrix of nanoparticles, we find that the anomalies are preserved. On the
      contrary, if the confinement is modeled by a disordered matrix of nanoparticles,
      we find a drastically different phase diagram: the LLPT shifts to lower pressures
      and temperatures, and the anomalies become weaker, as the disorder increases. We
      find that the density heterogeneities induced by the disordered matrix are
      responsible for the weakening of the LLPT and the disappearance of the anomalies.

PMID- 23005300
TI  - Distribution of maximum velocities in avalanches near the depinning transition.
AB  - We report exact predictions for universal scaling exponents and scaling functions
      associated with the distribution of the maximum collective avalanche propagation
      velocities v(m) in the mean field theory of the interface depinning transition.
      We derive the extreme value distribution P(v(m)|T) for the maximum velocities in
      avalanches of fixed duration T and verify the results by numerical simulation
      near the critical point. We find that the tail of the distribution of maximum
      velocity for an arbitrary avalanche duration, v(m), scales as P(v(m))~v(m)(-2)
      for large v(m). These results account for the observed power-law distribution of
      the maximum amplitudes in acoustic emission experiments of crystal plasticity and
      are also broadly applicable to other systems in the mean-field interface
      depinning universality class, ranging from magnets to earthquakes.

PMID- 23005301
TI  - Avalanches in strained amorphous solids: does inertia destroy critical behavior?
AB  - Simulations are used to determine the effect of inertia on athermal shear of
      amorphous two-dimensional solids. In the quasistatic limit, shear occurs through
      a series of rapid avalanches. The distribution of avalanches is analyzed using
      finite-size scaling with thousands to millions of disks. Inertia takes the system
      to a new underdamped universality class rather than driving the system away from
      criticality as previously thought. Scaling exponents are determined for the
      underdamped and overdamped limits and a critical damping that separates the two
      regimes. Systems are in the overdamped universality class even when most
      vibrational modes are underdamped.

PMID- 23005302
TI  - Shear flow of non-Brownian suspensions close to jamming.
AB  - The dynamical mechanisms controlling the rheology of dense suspensions close to
      jamming are investigated numerically, using simplified models for the relevant
      dissipative forces. We show that the velocity fluctuations control the
      dissipation rate and therefore the effective viscosity of the suspension. These
      fluctuations are similar in quasi-static simulations and for finite strain rate
      calculations with various damping schemes. We conclude that the statistical
      properties of grain trajectories-in particular the critical exponent of velocity
      fluctuations with respect to volume fraction phi-only weakly depend on the
      dissipation mechanism. Rather they are determined by steric effects, which are
      the main driving forces in the quasistatic simulations. The critical exponent of
      the suspension viscosity with respect to phi can then be deduced, and is
      consistent with experimental data.

PMID- 23005303
TI  - Mesoscale folding, instability, and disruption of laminar flow in metal surfaces.
AB  - Using in situ imaging, we report surface fold formation and fluidlike flow
      instabilities in sliding of annealed copper. We demonstrate using simulations
      that folding is principally driven by grain-induced plastic instability. The
      phenomenon shows remarkable similarities with Kelvin-Helmholtz-type flow
      instabilities in fluids. While such instabilities have been conjectured to exist
      in sliding interfaces at the nanoscale, we find vortices and folding in metals at
      the mesoscale. The occurrence of folds impacts many applications, including
      surface generation processes and tribology.

PMID- 23005304
TI  - Crystalline-vitreous interface in two dimensional silica.
AB  - The interface between a crystalline and a vitreous phase of a thin metal
      supported silica film was studied by low temperature scanning tunneling
      microscopy. The locally resolved evolution of Si-Si nearest neighbor distances
      and characteristic angles was evaluated across the border. Furthermore, we
      investigated the behavior of the ring size distribution close to the crystalline
      vitreous transition. The crystalline order was found to decay gradually within
      about 1.6 nm into the vitreous state.

PMID- 23005305
TI  - Evidence for Family-Meakin dynamical scaling in island growth and coalescence
      during vapor phase deposition.
AB  - Using real-time grazing-incidence small-angle x-ray scattering, we find that the
      processes of island formation and coalescence during the room-temperature vapor
      phase deposition of aluminum lead to dynamical scaling of the evolving surface
      morphology. The scaling is quantitatively consistent with the self-similarity
      predicted by the Family-Meakin model, which was developed to describe liquid
      droplet deposition, growth, and coalescence. The Family-Meakin model assumes only
      that atomic diffusion over the substrate between islands or droplets is
      negligible and that diffusion between impinging islands or droplets is sufficient
      to give complete coalescence. Therefore the dynamical scaling morphology
      evolution identified here may be common in the initial stages of those solid film
      growth processes which proceed by island formation and growth.

PMID- 23005306
TI  - Quantitative model of heterogeneous nucleation and growth of SiGe quantum dot
      molecules.
AB  - Using a multiscale approach combining continuum model with first-principles
      calculation, we develop a quantitative theoretical model for heterogeneous
      nucleation and the growth of a quantum dot molecule-a few islands "strain bonded"
      by a pit in heteroepitaxy of thin films, in contrast to homogeneous nucleation
      and growth of isolated strain islands on the surface. We show that the critical
      size and energy barrier for island nucleation next to a pit is substantially
      reduced with the increasing pit size, but the reduction approaches an upper bound
      of ~85% and ~72% for the size and barrier, respectively. Our model also predicts
      a self-limiting effect on island growth, resulting from an intriguing interplay
      between island-pit attraction and island-island repulsion, that drives the island
      size to increase linearly with the pit size, which explains a long-standing
      puzzle of experimental observation.

PMID- 23005307
TI  - Two-particle response in cluster dynamical mean-field theory: formalism and
      application to the Raman response of high-temperature superconductors.
AB  - A method is presented for the unbiased numerical computation of two-particle
      response functions of correlated electron materials via a solution of the
      dynamical mean-field equations in the presence of a perturbing field. The power
      of the method is demonstrated via a computation of the Raman B(1g) and B(2g)
      scattering intensities of the two-dimensional Hubbard model in parameter regimes
      believed to be relevant to high-temperature superconductivity. The theory
      reproduces the "two-magnon" peak characteristic of the Raman intensity of
      insulating parent compounds of high-T(c) copper oxide superconductors, and shows
      how it evolves to a quasiparticle response, as carriers are added. The method can
      be applied in any situation where a solution of equilibrium dynamical mean-field
      equations is feasible.

PMID- 23005308
TI  - Topological States and adiabatic pumping in quasicrystals.
AB  - The unrelated discoveries of quasicrystals and topological insulators have in
      turn challenged prevailing paradigms in condensed-matter physics. We find a
      surprising connection between quasicrystals and topological phases of matter: (i)
      quasicrystals exhibit nontrivial topological properties and (ii) these properties
      are attributed to dimensions higher than that of the quasicrystal. Specifically,
      we show, both theoretically and experimentally, that one-dimensional
      quasicrystals are assigned two-dimensional Chern numbers and, respectively,
      exhibit topologically protected boundary states equivalent to the edge states of
      a two-dimensional quantum Hall system. We harness the topological nature of these
      states to adiabatically pump light across the quasicrystal. We generalize our
      results to higher-dimensional systems and other topological indices. Hence,
      quasicrystals offer a new platform for the study of topological phases while
      their topology may better explain their surface properties.

PMID- 23005309
TI  - Relaxation in driven integer quantum Hall edge states.
AB  - A highly nonthermal electron distribution is generated when quantum Hall edge
      states originating from sources at different potentials meet at a quantum point
      contact. The relaxation of this distribution to a stationary form as a function
      of distance downstream from the contact has been observed in recent experiments
      [C. Altimiras et al., Phys. Rev. Lett. 105, 056803 (2010)]. Here we present an
      exact treatment of a minimal model for the system at filling factor nu=2, with
      results that account well for the observations.

PMID- 23005310
TI  - Andreev bound states in a one-dimensional topological superconductor.
AB  - We study the charge character of the Andreev bound states (ABSs) in one
      dimensional topological superconductors with spatial inversion symmetry (SIS)
      breaking. Despite the absence of the SIS, we show a hidden symmetry for the
      Bogoliubov-de Gennes equations around Fermi points in addition to the particle
      hole symmetry. This hidden symmetry protects that the charge of the ABSs is
      solely dependent on the corresponding Fermi velocities. On the other hand, if the
      SIS is present, the ABSs are charge neutral, similar to Majorana fermions. We
      also propose that the charge of the ABSs can be experimentally measured in the
      tunneling transport spectroscopy from the resonant differential tunneling
      conductance.

PMID- 23005311
TI  - Role of interchain coupling in the metallic state of conducting polymers.
AB  - We investigated the charge dynamics of the conductivity enhancement from 2 to
      1000 S/cm in poly(3, 4-ethylenedioxythiophene):poly(styrenesulfonate) as induced
      by structural changes through the addition of a polar solvent and the following
      solvent bath treatment. Our results indicate that the addition of a polar solvent
      selectively enhanced the pi-pi coupling of the polymer chains, resulting in the
      reduction of disorder and tremendously increasing the charge carrier mobility,
      which yielded an insulator-to-metal transition. In contrast, the following
      solvent bath treatment selectively enhanced the intergrain coupling, which did
      not affect the disorder or the mobility but increased the charge carrier density.
      Therefore, we demonstrate that the conduction-character defining disorder in this
      conducting polymer system is determined by the extent of interchain coupling.

PMID- 23005312
TI  - Unidirectional thermal effects in current-induced domain wall motion.
AB  - We report experimental evidence of thermal effects on the displacement of vortex
      walls in NiFe nanostrips. With the use of nanosecond current pulses, a
      unidirectional motion of the magnetic domain walls towards the hotter part of the
      nanostrips is observed, in addition to current-induced domain wall motion. By
      tuning the heat dissipation in the samples and modeling the heat diffusion, we
      conclude that this unidirectional motion can only be explained by the presence of
      a temperature profile along the nanostrip. A quantitative analysis of the
      experiments shows that, on top of the classical thermodynamic pressure on the
      domain wall, another force, probably the magnonic spin Seebeck effect, is
      displacing the domain walls.

PMID- 23005313
TI  - Disorder-assisted electron-phonon scattering and cooling pathways in graphene.
AB  - We predict that graphene is a unique system where disorder-assisted scattering
      (supercollisions) dominates electron-lattice cooling over a wide range of
      temperatures, up to room temperature. This is so because for momentum-conserving
      electron-phonon scattering the energy transfer per collision is severely
      constrained due to a small Fermi surface size. The characteristic T(3)
      temperature dependence and power-law cooling dynamics provide clear experimental
      signatures of this new cooling mechanism. The cooling rate can be changed by
      orders of magnitude by varying the amount of disorder providing means for a
      variety of new applications that rely on hot-carrier transport.

PMID- 23005314
TI  - Crossover from spin accumulation into interface states to spin injection in the
      germanium conduction band.
AB  - Electrical spin injection into semiconductors paves the way for exploring new
      phenomena in the area of spin physics and new generations of spintronic devices.
      However the exact role of interface states in the spin injection mechanism from a
      magnetic tunnel junction into a semiconductor is still under debate. In this
      Letter, we demonstrate a clear transition from spin accumulation into interface
      states to spin injection in the conduction band of n-Ge. We observe spin signal
      amplification at low temperature due to spin accumulation into interface states
      followed by a clear transition towards spin injection in the conduction band from
      200 K up to room temperature. In this regime, the spin signal is reduced to a
      value compatible with the spin diffusion model. More interestingly, the
      observation in this regime of inverse spin Hall effect in germanium generated by
      spin pumping and the modulation of the spin signal by a gate voltage clearly
      demonstrate spin accumulation in the germanium conduction band.

PMID- 23005315
TI  - Gapped bilayer graphene: a tunable strongly correlated band insulator.
AB  - We introduce the notion of the strongly correlated band insulator (SCI), where
      the lowest energy excitations are collective modes (excitons) rather than the
      single particles. We construct controllable 1/N expansion for SCI to describe
      their observable properties. A remarkable example of the SCI is bilayer graphene
      which is shown to be tunable between the SCI and usual weak coupling regime.

PMID- 23005316
TI  - Hanbury Brown-Twiss interference of anyons.
AB  - We present a study of a Hanbury Brown-Twiss interferometer realized with anyons.
      Such a device can directly probe entanglement and fractional statistics of
      initially uncorrelated particles. We calculate Hanbury Brown-Twiss cross
      correlations of Abelian Laughlin anyons. The correlations we calculate exhibit
      partial bunching similar to bosons, indicating a substantial statistical
      transmutation from the underlying electronic degrees of freedom. We also find
      qualitative differences between the anyonic signal and the corresponding bosonic
      or fermionic signals, indicating that anyons cannot be simply thought of as
      intermediate between bosons and fermions.

PMID- 23005317
TI  - Unconventional vortex states in nanoscale superconductors due to shape-induced
      resonances in the inhomogeneous cooper-pair condensate.
AB  - Vortex matter in mesoscopic superconductors is known to be strongly affected by
      the geometry of the sample. Here we show that in nanoscale superconductors with
      coherence length comparable to the Fermi wavelength the shape resonances of the
      order parameter results in an additional contribution to the quantum topological
      confinement-leading to unconventional vortex configurations. Our Bogoliubov-de
      Gennes calculations in a square geometry reveal a plethora of asymmetric, giant
      multivortex, and vortex-antivortex structures, stable over a wide range of
      parameters and which are very different from those predicted by the Ginzburg
      Landau theory. These unconventional states are relevant for high-T(c) nanograins,
      confined Bose-Einstein condensates, and graphene flakes with proximity-induced
      superconductivity.

PMID- 23005318
TI  - Experimental evidence of a phi Josephson junction.
AB  - We demonstrate experimentally the existence of Josephson junctions having a
      doubly degenerate ground state with an average Josephson phase psi=+/-phi. The
      value of phi can be chosen by design in the interval 0<phi<pi. The junctions used
      in our experiments are fabricated as 0-pi Josephson junctions of moderate
      normalized length with asymmetric 0 and pi regions. We show that (a) these phi
      Josephson junctions have two critical currents, corresponding to the escape of
      the phase psi from -phi and +phi states, (b) the phase psi can be set to a
      particular state by tuning an external magnetic field, or (c) by using a proper
      bias current sweep sequence. The experimental observations are in agreement with
      previous theoretical predictions.

PMID- 23005319
TI  - Strongly disordered TiN and NbTiN s-wave superconductors probed by microwave
      electrodynamics.
AB  - We probe the effects of strong disorder (2.4<k(F)l<8.6) on superconductivity in
      thin films of niobium titanium nitride and titanium nitride by measuring the
      microwave electrodynamics in coplanar waveguide resonators. We find a gradual
      evolution of the electromagnetic response with disorder, deviating from BCS
      theory, for both materials. This result can be understood as due to changes in
      the quasiparticle density of states, induced by the short elastic scattering
      length. The observations are consistent with a model using an effective pair
      breaker, dependent on the level of disorder.

PMID- 23005320
TI  - Spin-orbit-mediated manipulation of heavy-hole spin qubits in gated semiconductor
      nanodevices.
AB  - A novel spintronic nanodevice is proposed that is able to manipulate the single
      heavy-hole spin state in a coherent manner. It can act as a single quantum logic
      gate. The heavy-hole spin transformations are realized by transporting the hole
      around closed loops defined by metal gates deposited on top of the nanodevice.
      The device exploits Dresselhaus spin-orbit interaction, which translates the
      spatial motion of the hole into a rotation of the spin. The proposed quantum gate
      operates on subnanosecond time scales and requires only the application of a weak
      static voltage which allows for addressing heavy-hole spin qubits individually.
      Our results are supported by quantum mechanical time-dependent calculations
      within the four-band Luttinger-Kohn model.

PMID- 23005321
TI  - Incommensurate sinusoidal oxygen modulations in layered manganites La(1
      x)Sr(1+x)MnO4 (x>=0.5).
AB  - We have studied the incommensurate-ordered phase in overdoped La0.4Sr1.6MnO4 by
      resonant x-ray diffraction at the Mn K edge. Weak resonant superlattice (h+/-0.2
      h+/-0.2 0) and (h+/-0.4 h+/-0.4 0) reflections of the tetragonal structure were
      found below ~240 K. The energy, azimuth angle, and polarization dependencies of
      the resonant scattering have revealed sinusoidal modulations of the oxygen
      motions that are transverse and longitudinal to the tetragonal [110] direction.
      This result discards (Mn(3+),Mn(4+))-like stripe-type order but point to a charge
      density-modulation picture.

PMID- 23005322
TI  - Strong Dzyaloshinskii-Moriya interaction and origin of ferroelectricity in
      Cu2OSeO3.
AB  - By performing density functional calculations, we investigate the origin of the
      Skyrmion state and ferroelectricity in Cu2OSeO3. We find that the Dzyaloshinskii
      Moriya interactions between the two different kinds of Cu ions are extremely
      strong and induce the helical ground state and the Skyrmion state in the absence
      and presence of a magnetic field, respectively. On the basis of the general model
      for the spin-order induced polarization, we propose that the ferroelectric
      polarization of Cu2OSeO3 in the collinear ferrimagnetic state arises from an
      unusual mechanism, i.e., the single-spin-site contribution due to the spin-orbit
      coupling.

PMID- 23005323
TI  - Transport magnetic proximity effects in platinum.
AB  - Platinum (Pt) metal, being nonmagnetic and with a strong spin-orbit coupling
      interaction, has been central in detecting the pure spin current and establishing
      most of the recent spin-based phenomena. Magnetotransport measurements, both
      electrical and thermal, conclusively show strong ferromagnetic characteristics in
      thin Pt films on the ferromagnetic insulator due to the magnetic proximity
      effects. The pure spin current phenomena measured by Pt, including the inverse
      spin Hall and the spin Seebeck effects, are thus contaminated and not exclusively
      established.

PMID- 23005324
TI  - Coherent two-electron spin qubits in an optically active pair of coupled InGaAs
      quantum dots.
AB  - In semiconductors, the T2* coherence time of a single confined spin is limited
      either by the fluctuating magnetic environment (via the hyperfine interaction),
      or by charge fluctuations (via the spin-orbit interaction). We demonstrate that
      both limitations can be overcome simultaneously by using two exchange-coupled
      electron spins that realize a single decoherence-avoiding qubit. Using coherent
      population trapping, we generate a coherent superposition of the singlet and
      triplet states of an optically active quantum dot molecule, and show that the
      corresponding T2* may exceed 200 ns.

PMID- 23005325
TI  - Metal-insulator transition and orbital reconstruction in Mott-type quantum wells
      made of NdNiO3.
AB  - The metal-insulator transition and the underlying electronic and orbital
      structure in e(g)(1) quantum wells based on NdNiO3 were investigated by dc
      transport and resonant soft x-ray absorption spectroscopy. By comparing quantum
      wells of the same dimension but with two different confinement structures, we
      explicitly demonstrate that the quantum well boundary condition of correlated
      electrons is critical to selecting the many-body ground state. In particular, the
      long-range orderings and the metal-insulator transition are found to be strongly
      enhanced under quantum confinement by sandwiching NdNiO(3) with the wide-gap
      dielectric LaAlO(3), while they are suppressed when one of the interfaces is
      replaced by a surface (interface with vacuum). Resonant spectroscopy reveals that
      the reduced charge fluctuations in the sandwich structure are supported by the
      enhanced propensity to charge ordering due to the suppressed e(g) orbital
      splitting when interfaced with the confining LaAlO3 layer.

PMID- 23005326
TI  - Microscopic origin of large negative magnetoelectric coupling in
      Sr(1/2)Ba(1/2)MnO3.
AB  - With a combined ab initio density functional and model Hamiltonian approach we
      establish that in the recently discovered multiferroic phase of the manganite
      Sr(1/2)Ba(1/2)MnO3 the polar distortion of Mn and O ions is stabilized via
      enhanced in-plane Mn-O hybridizations. The magnetic superexchange interaction is
      very sensitive to the polar bond-bending distortion, and we find that this
      dependence directly causes a strong magnetoelectric coupling. This novel
      mechanism for multiferroicity is consistent with the experimentally observed
      reduced ferroelectric polarization upon the onset of magnetic ordering.

PMID- 23005327
TI  - Creation and destruction of morphotropic phase boundaries through electrical
      poling: a case study of lead-free (Bi(1/2)Na(1/2))TiO3-BaTiO3 piezoelectrics.
AB  - We report the first direct evidence that the morphotropic phase boundary in
      ferroelectric materials, along with the associated strong piezoelectricity, can
      be created, destroyed, or even replaced by another morphotropic phase boundary
      through phase transitions during electrical poling. The real-time evolution of
      crystal structure and domain morphology during the poling-induced phase
      transitions in (Bi(1/2)Na(1/2))TiO3}BaTiO3 is observed with in situ transmission
      electron microscopy. These observations elucidate the microstructural origin of
      the macroscopic piezoelectricity's dependence on the poling field and previously
      unexplained strain behaviors. This study demonstrates that the ferroelectric-to
      ferroelectric transitions during the poling process can completely alter the
      morphotropic phase boundaries and, hence, must be comprehensively investigated
      when interpreting the microscopic mechanism of macroscopic piezoelectric
      behaviors.

PMID- 23005328
TI  - Anomalous dielectric behavior of nanoconfined electrolytic solutions.
AB  - We report an anomalous dielectric effect of electrolytes under cylindrical
      nanoconfinement. In bulk phase, the decrease in the water dielectric constant
      (epsilon) with increasing salt concentration is well known, and is due to
      dielectric saturation. From molecular dynamic simulations of confined water and
      NaCl solutions, we show a dielectric anisotropy and an unexpected increase in
      epsilon(perpendicular) of NaCl solutions with respect to the confined pure liquid
      until a critical concentration is reached. We infer that this striking dielectric
      behavior results from the interplay between the effect of confinement and that of
      ions on the water hydrogen bonding network.

PMID- 23005329
TI  - Direct observation of smectic layers in thermotropic liquid crystals.
AB  - We demonstrate subnanometer resolution cryo-TEM imaging of smectic layers in the
      smectic and nematic phases of two bent-core liquid crystals. Our results show
      perfect periodicity over several hundred layers in the smectic phase and also
      provide the first direct evidence of smectic clusters on length scales of 30-50
      nm in a nematic liquid crystal. The results are corroborated with small angle x
      ray scattering measurements. The observation of smectic clusters in the nematic
      phase is of special interest in bent-core liquid crystals, where the smectic
      clusters are stable over wide temperature ranges, in contrast to the well-known
      pretransitional "cybotactic" clusters that appear only in the vicinity of a bulk
      smectic phase. The means to characterize and manipulate this nanoscale molecular
      order could open up completely new liquid crystal-based technologies.

PMID- 23005330
TI  - Herschel-Bulkley shearing rheology near the athermal jamming transition.
AB  - We consider the rheology of soft-core frictionless disks in two dimensions in the
      neighborhood of the athermal jamming transition. From numerical simulations of
      bidisperse, overdamped particles, we argue that the divergence of the viscosity
      below jamming is characteristic of the hard-core limit, independent of the
      particular soft-core interaction. We develop a mapping from soft-core to hard
      core particles that recovers all the critical behavior found in earlier scaling
      analyses. Using this mapping we derive a relation that gives the exponent of the
      nonlinear Herschel-Bulkley rheology above jamming in terms of the exponent of the
      diverging viscosity below jamming.

PMID- 23005331
TI  - Contractile stresses in cohesive cell layers on finite-thickness substrates.
AB  - Using a minimal model of cells or cohesive cell layers as continuum active
      elastic media, we examine the effect of substrate thickness and stiffness on
      traction forces exerted by strongly adhering cells. We obtain a simple expression
      for the length scale controlling the spatial variation of stresses in terms of
      cell and substrate parameters that describes the crossover between the thin and
      thick substrate limits. Our model is an important step towards a unified
      theoretical description of the dependence of traction forces on cell or colony
      size, acto-myosin contractility, substrate depth and stiffness, and strength of
      focal adhesions and makes experimentally testable predictions.

PMID- 23005332
TI  - Mechanism of margination in confined flows of blood and other multicomponent
      suspensions.
AB  - Flowing blood displays a phenomenon called margination, in which leukocytes and
      platelets are preferentially found near blood vessel walls, while erythrocytes
      are depleted from these regions. Here margination is investigated using direct
      hydrodynamic simulations of a binary suspension of stiff (s) and floppy (f)
      capsules, as well as a stochastic model that incorporates the key particle
      transport mechanisms in suspensions-wall-induced hydrodynamic migration and shear
      induced pair collisions. The stochastic model allows the relative importance of
      these two mechanisms to be directly evaluated and thereby indicates that
      margination, at least in the dilute case, is largely due to the differential
      dynamics of homogeneous (e.g. s-s) and heterogeneous (s-f) collisions.

PMID- 23005333
TI  - Control parameter description of eukaryotic chemotaxis.
AB  - The chemotaxis of eukaryotic cells depends both on the average concentration of
      the chemoattractant and on the steepness of its gradient. For the social amoeba
      Dictyostelium discoideum, we test quantitatively the prediction by Ueda and
      Shibata [Biophys. J. 93, 11 (2007)] that the efficacy of chemotaxis depends on a
      single control parameter only, namely, the signal-to-noise ratio (SNR),
      determined by the stochastic fluctuations of (i) the binding of the
      chemoattractant molecule to the transmembrane receptor and (ii) the intracellular
      activation of the effector of the signaling cascade. For SNR < or approximately
      equal to 1, the theory captures the experimental findings well, while for larger
      SNR noise sources further downstream in the signaling pathway need to be taken
      into account.

PMID- 23005334
TI  - Current-induced membrane discharge.
AB  - Possible mechanisms for overlimiting current (OLC) through aqueous ion-exchange
      membranes (exceeding diffusion limitation) have been debated for half a century.
      Flows consistent with electro-osmotic instability have recently been observed in
      microfluidic experiments, but the existing theory neglects chemical effects and
      remains to be quantitatively tested. Here, we show that charge regulation and
      water self-ionization can lead to OLC by "current-induced membrane discharge"
      (CIMD), even in the absence of fluid flow, in ion-exchange membranes much thicker
      than the local Debye screening length. Salt depletion leads to a large electric
      field resulting in a local pH shift within the membrane with the effect that the
      membrane discharges and loses its ion selectivity. Since salt co-ions, H(+) ions,
      and OH(-) ions contribute to OLC, CIMD interferes with electrodialysis (salt
      counterion removal) but could be exploited for current-assisted ion exchange and
      pH control. CIMD also suppresses the extended space charge that leads to electro
      osmotic instability, so it should be reconsidered in both models and experiments
      on OLC.

PMID- 23005335
TI  - Computation of the mean first-encounter time between the ends of a polymer chain.
AB  - Using a novel theoretical approach, we study the mean first-encounter time (MFET)
      between the two ends of a polymer. Previous approaches used various
      simplifications that reduced the complexity of the problem, leading, however, to
      incompatible results. We construct here for the first time a general theory that
      allows us to compute the MFET. The method is based on estimating the mean time
      for a Brownian particle to reach a narrow domain in the polymer configuration
      space. In dimension two and three, we find that the MFET depends mainly on the
      first eigenvalue of the associated Fokker-Planck operator and provide precise
      estimates that are confirmed by Brownian simulations. Interestingly, although
      many time scales are involved in the encounter process, its distribution can be
      well approximated by a single exponential, which has several consequences for
      modeling chromosome dynamics in the nucleus. Another application of our result is
      computing the mean time for a DNA molecule to form a closed loop (when its two
      ends meet for the first time).

PMID- 23005336
TI  - Confinement induced splay-to-bend transition of colloidal rods.
AB  - We study the nematic phase of rodlike f d-virus particles confined to channels
      with wedge-structured walls. Using laser scanning confocal microscopy we observe
      a splay-to-bend transition at the single particle level as a function of the
      wedge opening angle. Lattice Boltzmann simulations reveal the underlying origin
      of the transition and its dependence on nematic elasticity and wedge geometry.
      Our combined work provides a simple method to estimate the splay-to-bend
      elasticity ratios of the virus and offers a way to control the position of
      defects through the confining boundary conditions.

PMID- 23005337
TI  - Potential of sivelestat in protection against severe acute pancreatitis
      associated lung injury in rats.
AB  - The incidence of acute pancreatitis has been rising worldwide in the past few
      decades. Despite extensive research efforts, the population-based mortality from
      acute pancreatitis remains high. Since dysfunction of multiple vital organs, most
      importantly the lungs, is the major cause of early death in acute pancreatitis
      patients, developing effective strategies to manage lung injury has become one of
      the focuses of recent research efforts aiming at improving the outcome of
      patients with acute pancreatitis. In this study, we attempted to create a rat
      model of acute pancreatitis through intraductal infusion of taurocholate and to
      evaluate the potential of sivelestat, a synthetic neutrophil elastase inhibitor,
      in protection against acute pancreatitis-associated lung injury using this rat
      model. The results demonstrated that: (1) 5% sodium taurocholate successfully
      induced histopathologic and biochemical abnormalities in the circulation, lung
      and pancreas characteristic of human acute pancreatitis, including an increase in
      amylase concentration and a decrease in partial arterial oxygen pressure (PaO2)
      in the blood, increases in activities of myeloperoxidase (MPO) (a lung injury
      marker) and neutrophil elastase (a quantitative indicator of neutrophil
      infiltration), and levels of malondialdehyde (an indicator of lipid peroxidation)
      and tumor necrosis factor-alpha (a major inflammatory mediator) in the lung; (2)
      intravenous administration of sivelestat effectively attenuated the taurocholate
      induced abnormalities in all parameters analyzed except for serum amylase
      concentration. Our findings have validated the taurocholate model of acute
      pancreatitis and demonstrated great therapeutic potential for sivelestat in
      managing acute pancreatitis-associated lung injury.

PMID- 23005338
TI  - Stress induces a functional asymmetry in an emotional attention task.
AB  - Anxiety is associated with an attentional bias towards angry faces. This effect
      is most pronounced when the face is presented in the left visual hemifield
      (LVHF), suggestive of a right hemisphere involvement. Little is known about the
      modulation of this attentional bias in situations of acute stress. In the current
      study 38 male participants were randomly allocated to a stress (Trier Social
      Stress Test; TSST) or a non-stressful control condition. Afterwards they
      performed an emotional dot-probe paradigm. Stress induced negative affect and a
      rise in salivary cortisol. Stress caused a pattern of functional asymmetry in the
      short stimulus onset asynchrony (SOA) interval, which was absent in the control
      group. Stressed participants responded faster to angry faces presented to the
      LVHF, but responded faster to happy faces presented to the right VHF. This could
      suggest that stress influences interhemispheric transfer of information that is
      relevant for emotion processing.

PMID- 23005339
TI  - Ergonomics in the development and implementation of organisational strategy for
      sustainability.
AB  - This is the first phase of an ergonomics study of sustainability in a rail
      organisation, particularly environmental sustainability. The main emphasis has
      been on the use of a qualitative approach to carry out in-depth consultation with
      those in influential and policy setting roles in the organisation, collecting and
      analysing perceptions on sustainability policy and related business processes.
      The study identified factors affecting implementation of policy on sustainability
      and these have been developed to produce a list of requirements for implementing
      the policy. The findings are valuable in understanding the range of attitudes,
      aspirations and perceived constraints, from the perspective of those in senior
      roles in the company, and development of a sustainability strategy for a rail
      infrastructure owner. There is need for wider consultation, both within the
      organisation and externally, to validate and refine the understanding of barriers
      to the implementation of the policy. The role of ergonomics in supporting the
      work on sustainability is discussed. PRACTITIONER SUMMARY: The study collects in
      depth views from senior managers on the challenges of implementing a policy on
      sustainability in a rail organisation. Outputs include a list of factors
      affecting implementation of policy and requirements for better implementation of
      policy in this area. Potential contributions of ergonomics to sustainability in
      organisational contexts are discussed.

PMID- 23005340
TI  - Hydrogen bonding directed intermolecular Cope-type hydroamination of alkenes.
AB  - Intermolecular hydroamination of unactivated alkenes represents a significant
      synthetic challenge. An efficient Cope-type hydroamination is achieved under mild
      conditions for reactions of N-alkylhydroxylamines with allylic amines, using
      hydrogen bonding to achieve increased reactivity and high regioselectivity. This
      approach provides a number of highly functionalized vicinal diamine motifs as
      Markovnikov addition products.

PMID- 23005341
TI  - The small heat-shock protein alphaB-crystallin uses different mechanisms of
      chaperone action to prevent the amorphous versus fibrillar aggregation of alpha
      lactalbumin.
AB  - Stress conditions can destabilize proteins, promoting them to unfold and adopt
      intermediately folded states. Partially folded protein intermediates are unstable
      and prone to aggregation down off-folding pathways leading to the formation of
      either amorphous or amyloid fibril aggregates. The sHsp (small heat-shock
      protein) alphaB-crystallin acts as a molecular chaperone to prevent both
      amorphous and fibrillar protein aggregation; however, the precise molecular
      mechanisms behind its chaperone action are incompletely understood. To
      investigate whether the chaperone activity of alphaB-crystallin is dependent upon
      the form of aggregation (amorphous compared with fibrillar), bovine alpha
      lactalbumin was developed as a model target protein that could be induced to
      aggregate down either off-folding pathway using comparable buffer conditions.
      Thus when alpha-lactalbumin was reduced it aggregated amorphously, whereas a
      reduced and carboxymethylated form aggregated to form amyloid fibrils. Using this
      model, alphaB-crystallin was shown to be a more efficient chaperone against
      amorphously aggregating alpha-lactalbumin than when it aggregated to form
      fibrils. Moreover, alphaB-crystallin forms high molecular mass complexes with
      alpha-lactalbumin to prevent its amorphous aggregation, but prevents fibril
      formation via weak transient interactions. Thus, the conformational stability of
      the protein intermediate, which is a precursor to aggregation, plays a critical
      role in modulating the chaperone mechanism of alphaB-crystallin.

PMID- 23005342
TI  - Update 1 of: macrolactonizations in the total synthesis of natural products.

PMID- 23005344
TI  - Efficient fluorescence "turn-on" sensing of dissolved oxygen by electrochemical
      switching.
AB  - We report on a novel method for sensing oxygen that is based on the use of a
      perylene diimide dye (1) which is electrochemically reduced to its nonfluorescent
      dianion form (1(2-)). In the presence of oxygen, the dianion is oxidized to its
      initial form via an electron-transfer reaction with oxygen upon which
      fluorescence is recovered. As a result, the fluorescence intensity of the dianion
      solution increases upon the addition of oxygen gas. Results demonstrate that high
      sensitivity is obtained, and the emission intensity shows a linear correlation
      with oxygen content (0.0-4.0% v/v) at ambient barometric pressure. In addition,
      using electrochemical reduction, oxygen determination becomes regenerative, and
      no significant degradation is observed over several turnovers. The limit of
      detection is 0.4% oxygen in argon gas.

PMID- 23005343
TI  - Climate change alters stoichiometry of phosphorus and nitrogen in a semiarid
      grassland.
AB  - Nitrogen (N) and phosphorus (P) are essential nutrients for primary producers and
      decomposers in terrestrial ecosystems. Although climate change affects
      terrestrial N cycling with important feedbacks to plant productivity and carbon
      sequestration, the impacts of climate change on the relative availability of N
      with respect to P remain highly uncertain. In a semiarid grassland in Wyoming,
      USA, we studied the effects of atmospheric CO(2) enrichment (to 600 ppmv) and
      warming (1.5/3.0 degrees C above ambient temperature during the day/night) on
      plant, microbial and available soil pools of N and P. Elevated CO(2) increased P
      availability to plants and microbes relative to that of N, whereas warming
      reduced P availability relative to N. Across years and treatments, plant N : P
      ratios varied between 5 and 18 and were inversely related to soil moisture. Our
      results indicate that soil moisture is important in controlling P supply from
      inorganic sources, causing reduced P relative to N availability during dry
      periods. Both wetter soil conditions under elevated CO(2) and drier conditions
      with warming can further alter N : P. Although warming may alleviate N
      constraints under elevated CO(2) , warming and drought can exacerbate P
      constraints on plant growth and microbial activity in this semiarid grassland.

PMID- 23005345
TI  - Day zero quantitative mRNA analysis as a prognostic marker in pulmonary
      tuberculosis category II patients on treatment.
AB  - Mycobacterium tuberculosis m-RNA quantitation in sputum of pulmonary tuberculosis
      patients before starting supervised treatment was evaluated as a surrogate for
      response. Sputum specimens were collected from 50 patients (DOTS category II
      treatment; 303 specimens, day 0 to fourth month) and 16 controls (non-tubercular
      lung disorders). Microscopy, reverse-transcriptase PCR and DNA-PCR were compared
      with culture using the BACTEC 460 system. TaqMan real-time RT-PCR quantitated the
      mRNA levels. RT-PCR (sensitivity, 10 organisms/mL) and culture results were
      concordant. mRNA declined with time and correlated with culture clearance. Thirty
      nine (78%) patients were smear, culture and RT-PCR negative at 2 months of
      treatment. Day 0 mRNA levels had statistically significant correlation with time
      to culture conversion and drug resistance (p 0.041). Of seven patients with
      sensitive isolates but high m-RNA levels, four presented with re-infection/mixed
      infection later, while three presented with relapse (ninth to twentieth month).
      The control group specimens were negative for the above tests. M. tuberculosis
      mRNA in the sputum is a useful prognostic marker and its quantitation an early
      and reliable indicator for monitoring response, prediction of culture conversion,
      drug resistance, re-infection and relapse. mRNA quantitation may prove to be of
      great value for evaluating the response to new drugs under trial.

PMID- 23005346
TI  - Menstrual bleeding patterns and prevalence of bleeding disorders in a
      multidisciplinary adolescent haematology clinic.
AB  - Heavy menstrual bleeding (HMB) is a frequent complaint in adolescence. Although
      HMB is often caused by immaturity of the hypothalamic-pituitary-ovarian axis,
      bleeding disorders are another common yet often unidentified cause. The aim of
      this study was to examine the bleeding patterns and prevalence of inherited
      bleeding disorders among females referred for HMB to a multidisciplinary
      adolescent haematology clinic. We retrospectively reviewed the first 105 patients
      (ages 8-18 years) referred to this specialty clinic from February 2009 to
      December 2011. Using menstrual bleeding questionnaires and medical records, data
      were extracted regarding demographics, bleeding patterns, frequency and types of
      bleeding disorders identified, and prescribed interventions. Sixty-two per cent
      of patients were diagnosed with a bleeding disorder, including platelet storage
      pool deficiency (36%), von Willebrand's disease (9%), other platelet function
      defect (8%), Ehlers-Danlos syndrome (7%) and combined bleeding disorders (2%).
      Comparison of the bleeding profiles for females with and without a bleeding
      disorder revealed only three factors that were significantly different, including
      the reported regularity of patients' periods (P = 0.02), description of period
      flow (P = 0.04) and number of days of each period that the bleeding was described
      as 'heavy' (P = 0.007). Bleeding disorders are prevalent in adolescent females
      presenting to a specialty clinic. Specifically, a relatively high proportion of
      adolescents were diagnosed with platelet storage pool deficiency. In our small
      population, menstrual bleeding profiles, as examined by a standardized
      questionnaire, could not identify females with an underlying bleeding disorder,
      demonstrating the important role of haemostasis testing in the evaluation of
      adolescents with HMB.

PMID- 23005347
TI  - Testing of 'executive function'.

PMID- 23005350
TI  - Thermal rectification in graded materials.
AB  - In order to identify the basic conditions for thermal rectification we
      investigate a simple model with nonuniform, graded mass distribution. The
      existence of thermal rectification is theoretically predicted and numerically
      confirmed, suggesting that thermal rectification is a typical occurrence in
      graded systems, which are likely to be natural candidates for the actual
      fabrication of thermal diodes. In view of practical implications, the dependence
      of rectification on the asymmetry and system's size is studied.

PMID- 23005351
TI  - Weak and strong typicality in quantum systems.
AB  - We study the properties of mixed states obtained from eigenstates of many-body
      lattice Hamiltonians after tracing out part of the lattice. Two scenarios emerge
      for generic systems: (i) The diagonal entropy becomes equivalent to the
      thermodynamic entropy when a few sites are traced out (weak typicality); and (ii)
      the von Neumann (entanglement) entropy becomes equivalent to the thermodynamic
      entropy when a large fraction of the lattice is traced out (strong typicality).
      Remarkably, the results for few-body observables obtained with the reduced,
      diagonal, and canonical density matrices are very similar to each other, no
      matter which fraction of the lattice is traced out. Hence, for all physical
      quantities studied here, the results in the diagonal ensemble match the thermal
      predictions.

PMID- 23005348
TI  - Imaging metastasis using an integrin-targeting chain-shaped nanoparticle.
AB  - While the enhanced permeability and retention effect may promote the preferential
      accumulation of nanoparticles into well-vascularized primary tumors, it is
      ineffective in the case of metastases hidden within a large population of normal
      cells. Due to their small size, high dispersion to organs, and low
      vascularization, metastatic tumors are less accessible to targeted nanoparticles.
      To tackle these challenges, we designed a nanoparticle for vascular targeting
      based on an alpha(v)beta(3) integrin-targeted nanochain particle composed of four
      iron oxide nanospheres chemically linked in a linear assembly. The chain-shaped
      nanoparticles enabled enhanced "sensing" of the tumor-associated remodeling of
      the vascular bed, offering increased likelihood of specific recognition of
      metastatic tumors. Compared to spherical nanoparticles, the chain-shaped
      nanoparticles resulted in superior targeting of alpha(v)beta(3) integrin due to
      geometrically enhanced multivalent docking. We performed multimodal in vivo
      imaging (fluorescence molecular tomography and magnetic resonance imaging) in a
      non-invasive and quantitative manner, which showed that the nanoparticles
      targeted metastases in the liver and lungs with high specificity in a highly
      aggressive breast tumor model in mice.

PMID- 23005352
TI  - Derivation of quantum work equalities using a quantum Feynman-Kac formula.
AB  - On the basis of a quantum mechanical analog of the famous Feynman-Kac formula, we
      present a method to derive nonequilibrium work equalities for isolated quantum
      systems, which include the Jarzynski equality and Bochkov-Kuzovlev equality.
      Compared with other methods in the literature, our method shows a higher
      similarity in form to the method deriving the fluctuation relations in the
      classical systems.

PMID- 23005353
TI  - Branching-rate expansion around annihilating random walks.
AB  - We present some exact results for branching and annihilating random walks. We
      compute the nonuniversal threshold value of the annihilation rate for having a
      phase transition in the simplest reaction-diffusion system belonging to the
      directed percolation universality class. Also, we show that the accepted scenario
      for the appearance of a phase transition in the parity conserving universality
      class must be improved. In order to obtain these results we perform an expansion
      in the branching rate around pure annihilation, a theory without branching. This
      expansion is possible because we manage to solve pure annihilation exactly in any
      dimension.

PMID- 23005354
TI  - Phase transition in the countdown problem.
AB  - We present a combinatorial decision problem, inspired by the celebrated quiz show
      called Countdown, that involves the computation of a given target number T from a
      set of k randomly chosen integers along with a set of arithmetic operations. We
      find that the probability of winning the game evidences a threshold phenomenon
      that can be understood in the terms of an algorithmic phase transition as a
      function of the set size k. Numerical simulations show that such probability
      sharply transitions from zero to one at some critical value of the control
      parameter, hence separating the algorithm's parameter space in different phases.
      We also find that the system is maximally efficient close to the critical point.
      We derive analytical expressions that match the numerical results for finite size
      and permit us to extrapolate the behavior in the thermodynamic limit.

PMID- 23005355
TI  - Noise-induced metastability in biochemical networks.
AB  - Intracellular biochemical reactions exhibit a rich dynamical phenomenology which
      cannot be explained within the framework of mean-field rate equations and
      additive noise. Here, we show that the presence of metastable states and
      radically different time scales are general features of a broad class of
      autocatalytic reaction networks, and that this fact may be exploited to gain
      analytical results. The latter point is demonstrated by a treatment of the
      paradigmatic Togashi-Kaneko reaction, which has resisted theoretical analysis for
      the last decade.

PMID- 23005356
TI  - Stokes-Einstein diffusion of colloids in nematics.
AB  - We report the experimental observation of anisotropic diffusion of polystyrene
      particles immersed in a lyotropic liquid crystal with two different anchoring
      conditions. Diffusion is shown to obey the Stokes-Einstein law for particle
      diameters ranging from 190 nm up to 2 MUm. In the case of prolate micelles, the
      beads diffuse four times faster along the director than in perpendicular
      directions, D||/D[Symbol: see text] ~ 4. In the theory part we present a
      perturbative approach to the Leslie-Ericksen equations and relate the diffusion
      coefficients to the Miesovicz viscosity parameters eta(i). We provide explicit
      formulas for the cases of uniform director field and planar anchoring conditions
      which are then discussed in view of the data. As a general rule, we find that the
      inequalities eta(b) <eta(a) <eta(c), satisfied by various liquid crystals of
      rodlike molecules, imply D||>D[Symbol: see text].

PMID- 23005357
TI  - Simple nonlinear equation for structural relaxation in glasses.
AB  - A wide range of glassy and disordered materials exhibit complex, nonexponential,
      structural relaxation (aging). We propose a simple nonlinear rate equation delta
      = a[1-exp(b delta)], where delta is the normalized deviation of a macroscopic
      variable from its equilibrium value, to describe glassy relaxation. Analysis of
      extensive experimental data shows that this equation quantitatively captures
      structural relaxation, where a and b are both temperature- and, more importantly,
      history-dependent parameters. This analysis explicitly demonstrates that
      structural relaxation cannot be accurately described by a single nonequilibrium
      variable. Relaxation rates extracted from the data imply the existence of
      cooperative rearrangements on a supermolecular scale.

PMID- 23005358
TI  - Critical behavior in an electric-field-induced anchoring transition in a liquid
      crystal.
AB  - We report an anchoring transition of a liquid crystal under the influence of an
      electric field (E field) in the vicinity of a first-order anchoring transition
      (ATr) temperature showing bistable homeotropic (H) and planar (P) states. By
      means of polarizing microscopy combined with retardation and switching and
      dielectric measurements, three important observations were made: (1) The
      anchoring transition from H to P driven by an E field is first order with a
      threshold E-field strength, which decreases with increasing temperature; (2) the
      thickness of the H layer that is to be converted to the P orientation increases
      toward ATr temperature T(ATr); and (3) the temperature dependence of both
      parameters is well described by a power law.

PMID- 23005359
TI  - Block copolymer films with free interfaces: ordering by nanopatterned substrates.
AB  - We study block copolymers (BCPs) on patterned substrates, where the top polymer
      film surface is not constrained but is free and can adapt its shape self
      consistently. In particular, we investigate the combined effect of free interface
      undulations with wetting of the BCP film as induced by nanopatterned substrates.
      Under wetting conditions and for a finite volume of BCP material, we find
      equilibrium droplets composed of coexisting perpendicular and parallel lamellar
      domains. The self-assembly of BCPs on topographic patterned substrates is also
      investigated and it is found that the free interface induces mixed morphologies
      of parallel and perpendicular domains coupled with a nonflat free interface. Our
      study has some interesting consequences for experimental setups of graphoepitaxy
      and nanoimprint lithography.

PMID- 23005360
TI  - Processivity and collectivity of biomolecular motors extracting membrane
      nanotubes.
AB  - Biomolecular motors can pull and viscously drag membranes. The resulting
      elongations include cell protrusions, tether networks, and sensorial tentacles.
      Here we focus on the extraction of a single tube from a vesicle. Via a force
      balance coupled to binding kinetics, we analytically determine the phase diagram
      of tube formation as function of the motor processivity, the surface viscosity of
      the membrane eta'(m), and the density of motors on the vesicle rho. Three
      tubulation mechanisms are identified: (i) tip pulling, due to the accumulation of
      motors at the leading edge of the membrane, (ii) viscous drag, emergent from the
      translation of motors along the tube, and (iii) hybrid extraction, such that tip
      pulling and viscous drag are equally important. For experimental values of
      eta'(m) and rho, we find that the growth of bionanotubes tends to be driven by
      viscous forces, whereas artificial membranes are dominated by tip pulling.

PMID- 23005361
TI  - Effect of thermal noise on vesicles and capsules in shear flow.
AB  - We add thermal noise consistently to reduced models of undeformable vesicles and
      capsules in shear flow and derive analytically the corresponding stochastic
      equations of motion. We calculate the steady-state probability distribution
      function and construct the corresponding phase diagrams for the different
      dynamical regimes. For fluid vesicles, we predict that at small shear rates
      thermal fluctuations induce a tumbling motion for any viscosity contrast. For
      elastic capsules, due to thermal mixing, an intermittent regime appears in
      regions where deterministic models predict only pure tank treading or tumbling.

PMID- 23005362
TI  - Levy flights on the half line.
AB  - We study the probability distribution function (PDF) of the position of a Levy
      flight of index 0 < alpha < 2 in the presence of an absorbing wall at the origin.
      The solution of the associated fractional Fokker-Planck equation can be
      constructed using a perturbation scheme around the Brownian solution
      (corresponding to alpha = 2) as an expansion in epsilon = 2-alpha. We obtain an
      explicit analytical solution, exact at the first order in epsilon, which allows
      us to conjecture the precise asymptotic behavior of this PDF, including the first
      subleading corrections, for any alpha. Careful numerical simulations, as well as
      an exact computation for alpha = 1, confirm our conjecture.

PMID- 23005363
TI  - Organizing principles for dense packings of nonspherical hard particles: not all
      shapes are created equal.
AB  - We have recently devised organizing principles to obtain maximally dense packings
      of the Platonic and Archimedean solids and certain smoothly shaped convex
      nonspherical particles [Torquato and Jiao, Phys. Rev. E 81, 041310 (2010)]. Here
      we generalize them in order to guide one to ascertain the densest packings of
      other convex nonspherical particles as well as concave shapes. Our generalized
      organizing principles are explicitly stated as four distinct propositions. All of
      our organizing principles are applied to and tested against the most
      comprehensive set of both convex and concave particle shapes examined to date,
      including Catalan solids, prisms, antiprisms, cylinders, dimers of spheres, and
      various concave polyhedra. We demonstrate that all of the densest known packings
      associated with this wide spectrum of nonspherical particles are consistent with
      our propositions. Among other applications, our general organizing principles
      enable us to construct analytically the densest known packings of certain convex
      nonspherical particles, including spherocylinders, "lens-shaped" particles,
      square pyramids, and rhombic pyramids. Moreover, we show how to apply these
      principles to infer the high-density equilibrium crystalline phases of hard
      convex and concave particles. We also discuss the unique packing attributes of
      maximally random jammed packings of nonspherical particles.

PMID- 23005364
TI  - Stripe-tetragonal phase transition in the two-dimensional Ising model with dipole
      interactions: partition function zeros approach.
AB  - We have performed multicanonical simulations to study the critical behavior of
      the two-dimensional Ising model with dipole interactions. This study concerns the
      thermodynamic phase transitions in the range of the interaction delta where the
      phase characterized by striped configurations of width h = 1 is observed.
      Controversial results obtained from local update algorithms have been reported
      for this region, including the claimed existence of a second-order phase
      transition line that becomes first order above a tricritical point located
      somewhere between delta = 0.85 and 1. Our analysis relies on the complex
      partition function zeros obtained with high statistics from multicanonical
      simulations. Finite size scaling relations for the leading partition function
      zeros yield critical exponents nu that are clearly consistent with a single
      second-order phase transition line, thus excluding such a tricritical point in
      that region of the phase diagram. This conclusion is further supported by
      analysis of the specific heat and susceptibility of the orientational order
      parameter.

PMID- 23005365
TI  - Yang-Lee edge singularities from extended activity expansions of the dimer
      density for bipartite lattices of dimensionality 2 <= d <= 7.
AB  - We have extended, in most cases through 24th order, the series expansions of the
      dimer density in powers of the activity in the case of bipartite [(hyper)-simple
      cubic and (hyper)-body-centered-cubic] lattices of dimensionalities 2 <= d <= 7.
      A numerical analysis of these data yields estimates of the exponents
      characterizing the Yang-Lee edge singularities for lattice ferromagnetic spin
      models as d varies between the lower and the upper critical dimensionalities. Our
      results are consistent with, but more extensive and sometimes more accurate than,
      those obtained from the existing dimer series or from the estimates of related
      exponents for lattice animals, branched polymers, and fluids. We mention also
      that it is possible to obtain estimates of the dimer constants from our series
      for the various lattices.

PMID- 23005366
TI  - Phase transitions in the q-voter model with two types of stochastic driving.
AB  - We study a nonlinear q-voter model with stochastic driving on a complete graph.
      We investigate two types of stochasticity that, using the language of social
      sciences, can be interpreted as different kinds of nonconformity. From a social
      point of view, it is very important to distinguish between two types
      nonconformity, so-called anticonformity and independence. A majority of work has
      suggested that these social differences may be completely irrelevant in terms of
      microscopic modeling that uses tools of statistical physics and that both types
      of nonconformity play the role of so-called social temperature. In this paper we
      clarify the concept of social temperature and show that different types of noise
      may lead to qualitatively different emergent properties. In particular, we show
      that in the model with anticonformity the critical value of noise increases with
      parameter q, whereas in the model with independence the critical value of noise
      decreases with q. Moreover, in the model with anticonformity the phase transition
      is continuous for any value of q, whereas in the model with independence the
      transition is continuous for q <= 5 and discontinuous for q>5.

PMID- 23005367
TI  - Anisotropic anomalous diffusion modulated by log-periodic oscillations.
AB  - We introduce finite ramified self-affine substrates in two dimensions with a set
      of appropriate hopping rates between nearest-neighbor sites where the diffusion
      of a single random walk presents an anomalous anisotropic behavior modulated by
      log-periodic oscillations. The anisotropy is revealed by two different random
      walk exponents nu(x) and nu(y) in the x and y directions, respectively. The
      values of these exponents as well as the periods of the oscillations are obtained
      analytically and confirmed by Monte Carlo simulations.

PMID- 23005368
TI  - Scaling of seismic memory with earthquake size.
AB  - It has been observed that discrete earthquake events possess memory, i.e., that
      events occurring in a particular location are dependent on the history of that
      location. We conduct an analysis to see whether continuous real-time data also
      display a similar memory and, if so, whether such autocorrelations depend on the
      size of earthquakes within close spatiotemporal proximity. We analyze the seismic
      wave form database recorded by 64 stations in Japan, including the 2011 "Great
      East Japan Earthquake," one of the five most powerful earthquakes ever recorded,
      which resulted in a tsunami and devastating nuclear accidents. We explore the
      question of seismic memory through use of mean conditional intervals and
      detrended fluctuation analysis (DFA). We find that the wave form sign series show
      power-law anticorrelations while the interval series show power-law correlations.
      We find size dependence in earthquake autocorrelations: as the earthquake size
      increases, both of these correlation behaviors strengthen. We also find that the
      DFA scaling exponent alpha has no dependence on the earthquake hypocenter depth
      or epicentral distance.

PMID- 23005369
TI  - Nonequilibrium discrete nonlinear Schrodinger equation.
AB  - We study nonequilibrium steady states of the one-dimensional discrete nonlinear
      Schrodinger equation. This system can be regarded as a minimal model for the
      stationary transport of bosonic particles such as photons in layered media or
      cold atoms in deep optical traps. Due to the presence of two conserved
      quantities, namely, energy and norm (or number of particles), the model displays
      coupled transport in the sense of linear irreversible thermodynamics. Monte Carlo
      thermostats are implemented to impose a given temperature and chemical potential
      at the chain ends. As a result, we find that the Onsager coefficients are finite
      in the thermodynamic limit, i.e., transport is normal. Depending on the position
      in the parameter space, the "Seebeck coefficient" may be either positive or
      negative. For large differences between the thermostat parameters, density and
      temperature profiles may display an unusual nonmonotonic shape. This is due to
      the strong dependence of the Onsager coefficients on the state variables.

PMID- 23005370
TI  - Generalized fluctuation relation for power-law distributions.
AB  - Strong violations of existing fluctuation theorems may arise in nonequilibrium
      steady states characterized by distributions with power-law tails. The ratio of
      the probabilities of positive and negative fluctuations of equal magnitude
      behaves in an anomalous nonmonotonic way [H. Touchette and E. G. D. Cohen, Phys.
      Rev. E 76, 020101(R) (2007)]. Here, we propose an alternative definition of
      fluctuation relation (FR) symmetry that, in the power-law regime, is
      characterized by a monotonic linear behavior. The proposal is consistent with a
      large deviationlike principle. As an example, we study the fluctuations of the
      work done on a dragged particle immersed in a complex environment able to induce
      power-law tails. When the environment is characterized by spatiotemporal
      temperature fluctuations, distributions arising in nonextensive statistical
      mechanics define the work statistics. In that situation, we find that the FR
      symmetry is solely defined by the average bath temperature. The case of a dragged
      particle subjected to a Levy noise is also analyzed in detail.

PMID- 23005371
TI  - Thermally driven Casimir ratchet-oscillator system.
AB  - We study a fluctuation-driven ratchet-oscillator system that consists of two
      ratchet pinions in contact with thermal baths at different temperatures. Coupling
      between noncontact parts of the system is mediated by the Casimir force through a
      thin corrugated plate. Due to mutual rectification, the two ratchets achieve
      directed average motion in opposite directions. We numerically probe the average
      velocity, the Peclet number, and the thermal efficiency of the system as
      functions of the effective temperatures of the thermal baths and other important
      dimensionless control parameters. It is found that optimal parameter values exist
      which maximize the directed transport rate but with very low efficiency. We
      expect that the obtained results will help in the design of noncontact mechanical
      devices in the future.

PMID- 23005372
TI  - Straightforward quantum-mechanical derivation of the Crooks fluctuation theorem
      and the Jarzynski equality.
AB  - We obtain the Crooks and the Jarzynski nonequilibrium fluctuation relations using
      a direct quantum-mechanical approach for a finite system that is either isolated
      or coupled not too strongly to a heat bath. These results were hitherto derived
      mostly in the classical limit. The two main ingredients in the picture are the
      time-reversal symmetry and the application of the first law to the case where an
      agent performs work on the system. No further assumptions regarding stochastic or
      Markovian behavior are necessary, neither a master equation or a classical phase
      space picture are required. The simplicity and the generality of these
      nonequilibrium relations are demonstrated, giving very simple insights into the
      physics.

PMID- 23005373
TI  - Evaluating transport in irregular pore networks.
AB  - A general approach for investigating transport phenomena in porous media is
      presented. This approach has the capacity to represent various kinds of
      irregularity in porous media without the need for excessive detail or
      computational effort. The overall method combines a generalized effective medium
      approximation (EMA) with a macroscopic continuum model in order to derive a
      transport equation with explicit analytical expressions for the transport
      coefficients. The proposed form of the EMA is an anisotropic and heterogeneous
      extension of Kirkpatrick's EMA [Rev. Mod. Phys. 45, 574 (1973)] which allows the
      overall model to account for microscopic alterations in connectivity (with the
      locations of the pores and the orientation and length of the throat) as well as
      macroscopic variations in transport properties. A comparison to numerical results
      for randomly generated networks with different properties is given, indicating
      the potential for this methodology to handle cases that would pose significant
      difficulties to many other analytical models.

PMID- 23005374
TI  - Conditional imitation might promote cooperation under high temptations to defect.
AB  - In this paper we introduce a conditional imitation rule into an evolutionary
      game, in which the imitation probabilities of individuals are determined by a
      function of payoff difference and two crucial parameters MU and sigma. The
      parameter MU characterizes the most adequate goal for individuals and the
      parameter sigma characterizes the tolerance of individuals. By using the pair
      approximation method and numerical simulations, we find an anomalous cooperation
      enhancement in which the cooperation level shows a nonmonotonic variation with
      the increase of temptation. The parameter MU affects the regime of the payoff
      parameter which supports the anomalous cooperation enhancement, whereas the
      parameter sigma plays a decisive role on the appearance of the nonmonotonic
      variation of the cooperation level. Furthermore, to give explicit implications
      for the parameters MU and sigma we present an alterative form of the conditional
      imitation rule based on the benefit and the cost incurred to individuals during
      strategy updates. In this way, we also provide a phenomenological interpretation
      for the nonmonotonic behavior of cooperation with the increase of temptation. The
      results give a clue that a higher cooperation level could be obtained under
      adverse environments for cooperation by applying the conditional imitation rule,
      which is possible to be manipulated in real life. More generally, the results in
      this work might point out an efficient way to maintain cooperation in the risky
      environments to cooperators.

PMID- 23005375
TI  - Extraction of stochastic dynamics from time series.
AB  - We present a method for the reconstruction of the dynamics of processes with
      discrete time. The time series from such a system is described by a stochastic
      recurrence equation, the continuous form of which is known as the Langevin
      equation. The deterministic f and stochastic g components of the stochastic
      equation are directly extracted from the measurement data with the assumption
      that the noise has finite moments and has a zero mean and a unit variance. No
      other information about the noise distribution is needed. This is contrary to the
      usual Langevin description, in which the additional assumption that the noise is
      Gaussian (delta-correlated) distributed as necessary. We test the method using
      one dimensional deterministic systems (the tent and logistic maps) with Gaussian
      and with Gumbel noise. In addition, results for human heart rate variability are
      presented as an example of the application of our method to real data. The
      differences between cardiological cases can be observed in the properties of the
      deterministic part f and of the reconstructed noise distribution.

PMID- 23005376
TI  - Statistical description of small quantum systems beyond the weak-coupling limit.
AB  - An explicit expression is derived for the statistical description of small
      quantum systems, which are relatively weakly and directly coupled to only small
      parts of their environments. The derived expression has a canonical form, but is
      given by a renormalized self-Hamiltonian of the studied system, which
      appropriately takes into account the influence of the system-environment
      interaction. In the case that the system has a narrow spectrum and the
      environment is sufficiently large, the modification to the self-Hamiltonian
      usually has a mean-field feature, given by an environmental average of the
      interaction Hamiltonian. In other cases, the modification may be beyond the mean
      field approximation.

PMID- 23005377
TI  - Encoding universal computation in the ground states of Ising lattices.
AB  - We characterize the set of ground states that can be synthesized by classical two
      body Ising Hamiltonians. We then construct simple Ising planar blocks that
      simulate efficiently a universal set of logic gates and connections, and hence
      any Boolean function. We therefore provide a new method of encoding universal
      computation in the ground states of Ising lattices and a simpler alternative
      demonstration of the known fact that finding the ground state of a finite Ising
      spin glass model is NP complete. We relate this with our previous result about
      emergent properties in infinite lattices.

PMID- 23005378
TI  - Corrections to scaling for watersheds, optimal path cracks, and bridge lines.
AB  - We study the corrections to scaling for the mass of the watershed, the bridge
      line, and the optimal path crack in two and three dimensions (2D and 3D). We
      disclose that these models have numerically equivalent fractal dimensions and
      leading correction-to-scaling exponents. We conjecture all three models to
      possess the same fractal dimension, namely, d(f) =1.2168 +/- 0.0005 in 2D and
      d(f) = 2.487 +/- 0.003 in 3D, and the same exponent of the leading correction,
      Omega = 0.9 +/- 0.1 and Omega=1.0 +/- 0.1, respectively. The close relations
      between watersheds, optimal path cracks in the strong disorder limit, and bridge
      lines are further supported by either heuristic or exact arguments.

PMID- 23005379
TI  - Agglomerative percolation on bipartite networks: nonuniversal behavior due to
      spontaneous symmetry breaking at the percolation threshold.
AB  - Ordinary bond percolation (OP) can be viewed as a process where clusters grow by
      joining them pairwise, adding links chosen randomly one by one from a set of
      predefined virtual links. In contrast, in agglomerative percolation (AP) clusters
      grow by choosing randomly a target cluster and joining it with all its neighbors,
      as defined by the same set of virtual links. Previous studies showed that AP is
      in different universality classes from OP for several types of (virtual) networks
      (linear chains, trees, Erdos-Renyi networks), but most surprising were the
      results for two-dimensional (2D) lattices: While AP on the triangular lattice was
      found to be in the OP universality class, it behaved completely differently on
      the square lattice. In the present paper we explain this striking violation of
      universality by invoking bipartivity. While the square lattice is a bipartite
      graph, the triangular lattice is not. In conformity with this we show that AP on
      the honeycomb and simple cubic (3D) lattices--both of which are bipartite--are
      also not in the OP universality classes. More precisely, we claim that this
      violation of universality is basically due to a Z(2) symmetry that is
      spontaneously broken at the percolation threshold. We also discuss AP on
      bipartite random networks and suitable generalizations of AP on k-partite graphs.

PMID- 23005380
TI  - Record statistics for multiple random walks.
AB  - We study the statistics of the number of records R(n,N) for N identical and
      independent symmetric discrete-time random walks of n steps in one dimension, all
      starting at the origin at step 0. At each time step, each walker jumps by a
      random length drawn independently from a symmetric and continuous distribution.
      We consider two cases: (I) when the variance sigma(2) of the jump distribution is
      finite and (II) when sigma(2) is divergent as in the case of Levy flights with
      index 0<MU<2. In both cases we find that the mean record number R(n,N) grows
      universally as ~alpha(N) sqrt[n] for large n, but with a very different behavior
      of the amplitude alpha(N) for N>1 in the two cases. We find that for large N,
      alpha(N) ~ 2sqrt[lnN] independently of sigma(2) in case I. In contrast, in case
      II, the amplitude approaches to an N-independent constant for large N, alpha(N) ~
      4/sqrt[pi], independently of 0<MU<2. For finite sigma(2) we argue-and this is
      confirmed by our numerical simulations-that the full distribution of
      (R(n,N)/sqrt[n]-2sqrt[lnN])sqrt[lnN] converges to a Gumbel law as n -> infinity
      and N -> infinity. In case II, our numerical simulations indicate that the
      distribution of R(n,N)/sqrt[n] converges, for n -> infinity and N -> infinity, to
      a universal nontrivial distribution independently of MU. We discuss the
      applications of our results to the study of the record statistics of 366 daily
      stock prices from the Standard & Poor's 500 index.

PMID- 23005381
TI  - Smart random walkers: the cost of knowing the path.
AB  - In this work we study the problem of targeting signals in networks using entropy
      information measurements to quantify the cost of targeting. We introduce a
      penalization rule that imposes a restriction on the long paths and therefore
      focuses the signal to the target. By this scheme we go continuously from fully
      random walkers to walkers biased to the target. We found that the optimal degree
      of penalization is mainly determined by the topology of the network. By analyzing
      several examples, we have found that a small amount of penalization reduces
      considerably the typical walk length, and from this we conclude that a network
      can be efficiently navigated with restricted information.

PMID- 23005382
TI  - Symbiotic two-species contact process.
AB  - We study a contact process (CP) with two species that interact in a symbiotic
      manner. In our model, each site of a lattice may be vacant or host individuals of
      species A and/or B; multiple occupancy by the same species is prohibited.
      Symbiosis is represented by a reduced death rate MU<1 for individuals at sites
      with both species present. Otherwise, the dynamics is that of the basic CP, with
      creation (at vacant neighbor sites) at rate lambda and death of (isolated)
      individuals at a rate of unity. Mean-field theory and Monte Carlo simulation show
      that the critical creation rate lambda(c)(MU) is a decreasing function of MU,
      even though a single-species population must go extinct for lambda<lambda(c) (1),
      the critical point of the basic CP. Extensive simulations yield results for
      critical behavior that are compatible with the directed percolation (DP)
      universality class, but with unusually strong corrections to scaling. A field
      theoretic argument supports the conclusion of DP critical behavior. We obtain
      similar results for a CP with creation at second-neighbor sites and enhanced
      survival at first neighbors in the form of an annihilation rate that decreases
      with the number of occupied first neighbors.

PMID- 23005383
TI  - Canonical formulation of quantum dissipation and noise in a generalized spin
      bath.
AB  - The quantum dynamics of a particle coupled to the dissipative degrees of freedom
      of a generalized spin bath in the presence of an external force field is
      presented. Based on Holstein-Primakoff transformation, which sets up a mapping
      between boson and spin operators, we show that the spin-1/2 bath and the harmonic
      bath can be realized as two special limits of the generalized bath. In the large
      spin limit, the Hamiltonian reduces to well-known Zwanzig Hamiltonian. Making use
      of spin coherent states and canonical thermal distributions of the associated c
      numbers, we derive and explore the quantum Langevin equation and the properties
      of the spin and harmonic baths in the context of quantum dissipation of the
      system.

PMID- 23005384
TI  - Anomalous critical behavior in the polymer collapse transition of three
      dimensional lattice trails.
AB  - Trails (bond-avoiding walks) provide an alternative lattice model of polymers to
      self-avoiding walks, and adding self-interaction at multiply visited sites gives
      a model of polymer collapse. Recently a two-dimensional model (triangular
      lattice) where doubly and triply visited sites are given different weights was
      shown to display a rich phase diagram with first- and second-order collapse
      separated by a multicritical point. A kinetic growth process of trails (KGTs) was
      conjectured to map precisely to this multicritical point. Two types of low
      temperature phases, a globule phase and a maximally dense phase, were
      encountered. Here we investigate the collapse properties of a similar extended
      model of interacting lattice trails on the simple cubic lattice with separate
      weights for doubly and triply visited sites. Again we find first- and second
      order collapse transitions dependent on the relative sizes of the doubly and
      triply visited energies. However, we find no evidence of a low-temperature
      maximally dense phase with only the globular phase in existence. Intriguingly,
      when the ratio of the energies is precisely that which separates the first-order
      from the second-order regions anomalous finite-size scaling appears. At the
      finite-size location of the rounded transition clear evidence exists for a first
      order transition that persists in the thermodynamic limit. This location moves as
      the length increases, with its limit apparently at the point that maps to a KGT.
      However, if one fixes the temperature to sit at exactly this KGT point, then only
      a critical point can be deduced from the data. The resolution of this apparent
      contradiction lies in the breaking of crossover scaling and the difference in the
      shift and transition width (crossover) exponents.

PMID- 23005385
TI  - Spatial pattern formation in external noise: theory and simulation.
AB  - Spatial pattern formation in fluctuating media is researched analytically from
      the point of view of the order parameters concept. A reaction-diffusion system
      with external noise is considered as a model of such media. Stochastic equations
      for unstable mode amplitudes (order parameters), the dispersion equation for
      averaged amplitudes of unstable modes, and the Fokker-Planck equation for the
      order parameters are obtained. The theory developed makes it possible to analyze
      different noise-induced effects including the variation of boundaries of ordering
      and disordering phase transitions depending on the parameters of external noise.

PMID- 23005386
TI  - Dynamics of the chemical master equation, a strip of chains of equations in d
      dimensional space.
AB  - We investigate the multichain version of the chemical master equation, when there
      are transitions between different states inside the long chains, as well as
      transitions between (a few) different chains. In the discrete version, such a
      model can describe the connected diffusion processes with jumps between different
      types. We apply the Hamilton-Jacobi equation to solve some aspects of the model.
      We derive exact (in the limit of infinite number of particles) results for the
      dynamic of the maximum of the distribution and the variance of distribution.

PMID- 23005387
TI  - Two-scale renormalization-group classification of diffusive processes.
AB  - Renormalization-group operators are used to classify stochastic processes on two
      time scales. Repeated application of one operator is associated with the long
      time behavior of the process while the other is associated with the short-time
      behavior of the process. This approach is shown to be robust even in the presence
      of nonstationary increments and infinite second moments. Fixed points of the
      operators can be used for further subclassification of processes when appropriate
      limits exist. Several processes are classified using the renormalization-group
      scheme. The processes to be classified include advection-diffusion in an ergodic
      velocity field, and a model of diffusion in the human bronchial tree.

PMID- 23005388
TI  - Coefficient of performance at maximum figure of merit and its bounds for low
      dissipation Carnot-like refrigerators.
AB  - The figure of merit for refrigerators performing finite-time Carnot-like cycles
      between two reservoirs at temperature T(h) and T(c) (<T(h)) is optimized. It is
      found that the coefficient of performance at maximum figure of merit is bounded
      between 0 and (sqrt[9+8epsilon(c)] - 3)/2 for the low-dissipation refrigerators,
      where epsilon(c) = T(c)/(T(h) - T(c)) is the Carnot coefficient of performance
      for reversible refrigerators. These bounds can be reached for extremely
      asymmetric low-dissipation cases when the ratio between the dissipation constants
      of the processes in contact with the cold and hot reservoirs approaches to zero
      or infinity, respectively. The observed coefficients of performance for real
      refrigerators are located in the region between the lower and upper bounds, which
      is in good agreement with our theoretical estimation.

PMID- 23005389
TI  - Discontinuous percolation transitions in epidemic processes, surface depinning in
      random media, and Hamiltonian random graphs.
AB  - Discontinuous percolation transitions and the associated tricritical points are
      manifest in a wide range of both equilibrium and nonequilibrium cooperative
      phenomena. To demonstrate this, we present and relate the continuous and first
      order behaviors in two different classes of models: The first are generalized
      epidemic processes that describe in their spatially embedded version--either on
      or off a regular lattice--compact or fractal cluster growth in random media at
      zero temperature. A random graph version of these processes is mapped onto a
      model previously proposed for complex social contagion. We compute detailed phase
      diagrams and compare our numerical results at the tricritical point in d = 3 with
      field theory predictions of Janssen et al. [Phys. Rev. E 70, 026114 (2004)]. The
      second class consists of exponential ("Hamiltonian," i.e., formally equilibrium)
      random graph models and includes the Strauss and the two-star model, where
      "chemical potentials" control the densities of links, triangles, or two-stars.
      When the chemical potentials in either graph model are O(logN), the percolation
      transition can coincide with a first-order phase transition in the density of
      links, making the former also discontinuous. Hysteresis loops can then be of
      mixed order, with second-order behavior for decreasing link fugacity, and a jump
      (first order) when it increases.

PMID- 23005390
TI  - Achlioptas processes are not always self-averaging.
AB  - We consider a class of percolation models, called Achlioptas processes, discussed
      in Science 323, 1453 (2009) and Science 333, 322 (2011). For these, the evolution
      of the order parameter (the rescaled size of the largest connected component) has
      been the main focus of research in recent years. We show that, in striking
      contrast to "classical" models, self-averaging is not a universal feature of
      these new percolation models: there are natural Achlioptas processes whose order
      parameter has random fluctuations that do not disappear in the thermodynamic
      limit.

PMID- 23005391
TI  - Dephasing by a continuous-time random walk process.
AB  - Stochastic treatments of magnetic resonance spectroscopy and optical spectroscopy
      require evaluations of functions such as (exp(i ?(0)(t) Q(s)ds)), where t is
      time, Q(s) is the value of a stochastic process at time s, and the angular
      brackets denote ensemble averaging. This paper gives an exact evaluation of these
      functions for the case where Q is a continuous-time random walk process. The
      continuous-time random walk describes an environment that undergoes slow steplike
      changes in time. It also has a well-defined Gaussian limit and so allows for non
      Gaussian and Gaussian stochastic dynamics to be studied within a single
      framework. We apply the results to extract qubit-lattice interaction parameters
      from dephasing data of P-doped Si semiconductors (data collected elsewhere) and
      to calculate the two-dimensional spectrum of a three-level harmonic oscillator
      undergoing random frequency modulations.

PMID- 23005392
TI  - Synchronization of globally coupled two-state stochastic oscillators with a state
      dependent refractory period.
AB  - We present a model of identical coupled two-state stochastic units, each of which
      in isolation is governed by a fixed refractory period. The nonlinear coupling
      between units directly affects the refractory period, which now depends on the
      global state of the system and can therefore itself become time dependent. At
      weak coupling the array settles into a quiescent stationary state. Increasing
      coupling strength leads to a saddle node bifurcation, beyond which the quiescent
      state coexists with a stable limit cycle of nonlinear coherent oscillations. We
      explicitly determine the critical coupling constant for this transition.

PMID- 23005393
TI  - Double stochastic resonance in the mean-field q-state clock model.
AB  - A magnetic system with a phase transition at temperature T(c) may exhibit double
      resonance peaks under a periodic external magnetic field because the time scale
      matches the external frequency at two different temperatures, one above T(c) and
      the other below T(c). We study the double-resonance phenomena for the mean-field
      q-state clock model based on the heat-bath-type master equation. We find double
      peaks as observed in the kinetic Ising case (q = 2) for all q >= 4, but for the
      three-state clock model (q = 3), the existence of double peaks is possible only
      above a certain external frequency since it undergoes a discontinuous phase
      transition.

PMID- 23005394
TI  - Stochastic resonance in multistable systems: the role of dimensionality.
AB  - The theory of stochastic resonance in multistable systems is extended to account
      for both direct transitions between all stable states present and indirect ones
      involving intermediate states. It is shown that to satisfy these requirements the
      dynamics needs to be embedded in phase spaces of dimension equal to at least two.
      Under well defined conditions, the conjunction of the presence of intermediate
      states and the multidimensional character of the process leads to an enhancement
      of the response of the system to an external periodic forcing.

PMID- 23005395
TI  - Stochastic dynamics of the prisoner's dilemma with cooperation facilitators.
AB  - In the framework of the paradigmatic prisoner's dilemma game, we investigate the
      evolutionary dynamics of social dilemmas in the presence of "cooperation
      facilitators." In our model, cooperators and defectors interact as in the
      classical prisoner's dilemma, where selection favors defection. However, here the
      presence of a small number of cooperation facilitators enhances the fitness
      (reproductive potential) of cooperators, while it does not alter that of
      defectors. In a finite population of size N, the dynamics of the prisoner's
      dilemma with facilitators is characterized by the probability that cooperation
      takes over (fixation probability) by the mean times to reach the absorbing
      states. These quantities are computed exactly using Fokker-Planck equations. Our
      findings, corroborated by stochastic simulations, demonstrate that the influence
      of facilitators crucially depends on the difference between their density z and
      the game's cost-to-benefit ratio r. When z > r, the fixation of cooperators is
      likely in a large population and, under weak selection pressure, invasion and
      replacement of defection by cooperation is favored by selection if b(z - r)(1 -
      z) > N(-1), where 0<b <= 1 is the cooperation payoff benefit. When z < r, the
      fixation probability of cooperators is exponentially enhanced by the presence of
      facilitators but defection is the dominating strategy.

PMID- 23005396
TI  - Detection of a long-range correlation with an adaptive detrending method.
AB  - We propose a methodology of estimating the scaling exponent for a long-range
      correlation in a nonstationary time series from the perspective of the regression
      analysis. By an adaptive degree determination of a regression polynomial, the
      proposed methodology is designed to properly remove various types of trends
      embedded in the nonstationary signal so that the scaling exponent can be
      estimated without artificial crossovers. To show the validity of the proposed
      methodology, we applied it to the detrended fluctuation analysis and tested it
      out against correlated data superimposed by various types of trends. It turned
      out that, unlike the conventional technique, our approach was capable of
      eliminating artificial crossovers. We also discuss the statistical
      characteristics of the proposed method with regard to the estimation of the
      scaling exponent.

PMID- 23005397
TI  - Thermal and athermal three-dimensional swarms of self-propelled particles.
AB  - Swarms of self-propelled particles exhibit complex behavior that can arise from
      simple models, with large changes in swarm behavior resulting from small changes
      in model parameters. We investigate the steady-state swarms formed by self
      propelled Morse particles in three dimensions using molecular dynamics
      simulations optimized for graphics processing units. We find a variety of swarms
      of different overall shape assemble spontaneously and that for certain Morse
      potential parameters at most two competing structures are observed. We report a
      rich "phase diagram" of athermal swarm structures observed across a broad range
      of interaction parameters. Unlike the structures formed in equilibrium self
      assembly, we find that the probability of forming a self-propelled swarm can be
      biased by the choice of initial conditions. We investigate how thermal noise
      influences swarm formation and demonstrate ways it can be exploited to
      reconfigure one swarm into another. Our findings validate and extend previous
      observations of self-propelled Morse swarms and highlight open questions for
      predictive theories of nonequilibrium self-assembly.

PMID- 23005398
TI  - Demographic noise and piecewise deterministic Markov processes.
AB  - We explore a class of hybrid (piecewise deterministic) systems characterized by a
      large number of individuals inhabiting an environment whose state is described by
      a set of continuous variables. We use analytical and numerical methods from
      nonequilibrium statistical mechanics to study the influence that intrinsic noise
      has on the qualitative behavior of the system. We discuss the application of
      these concepts to the case of semiarid ecosystems. Using a system-size expansion
      we calculate the power spectrum of the fluctuations in the system. This predicts
      the existence of noise-induced oscillations.

PMID- 23005399
TI  - Fermionic oscillator in a fermionic bath.
AB  - The quantum dissipation of a fermionic oscillator in an environment of fermionic
      oscillators is considered. Since fermions anticommute, their eigenvalues are
      anticommuting numbers. Based on an expansion of the reduced density operator in
      terms of fermionic coherent states which make use of these anticommuting numbers
      or Grassmann variables, a Fokker-Planck equation for the associated
      quasiprobability distribution function is derived. The density operator approach
      to fermionic fields as introduced by Cahill and Glauber [Phys. Rev. A 59, 1538
      (1999)] thus can be extended to the nonequilibrium domain.

PMID- 23005400
TI  - High-temperature expansions of the higher susceptibilities for the Ising model in
      general dimension d.
AB  - The high-temperature expansion coefficients of the ordinary and the higher
      susceptibilities of the spin-1/2 nearest-neighbor Ising model are calculated
      exactly up to the 20th order for the general d-dimensional (hyper)simple-cubical
      lattices. These series are analyzed to study the dependence of critical
      parameters on the lattice dimensionality. Using the general d expression of the
      ordinary susceptibility, we have more than doubled the length of the existing
      series expansion of the critical temperature in powers of 1/d.

PMID- 23005401
TI  - Monte Carlo study of the triangular Blume-Capel model under bond randomness.
AB  - The effects of bond randomness on the universality aspects of a two-dimensional
      (d = 2) Blume-Capel model embedded in the triangular lattice are discussed. The
      system is studied numerically in both its first- and second-order phase
      transition regimes by a comprehensive finite-size scaling analysis for a
      particularly suitable value of the disorder strength. We find that our data for
      the second-order phase transition, emerging under random bonds from the second
      order regime of the pure model, are compatible with the universality class of the
      two-dimensional (2D) random Ising model. Furthermore, we find evidence that, the
      second-order transition emerging under bond randomness from the first-order
      regime of the pure model, belongs again to the same universality class. Although
      the first finding reinforces the scenario of strong universality in the 2D Ising
      model with quenched disorder, the second is in difference from the critical
      behavior, emerging under randomness, in the cases of the ex-first-order
      transitions of the Potts model. Finally, our results verify previous
      renormalization-group calculations on the Blume-Capel model with disorder in the
      crystal-field coupling.

PMID- 23005402
TI  - Generalized Caroli formula for the transmission coefficient with lead-lead
      coupling.
AB  - We present a generalized transmission coefficient formula for the lead-junction
      lead system, in which interaction between the leads has been taken into account.
      Based on this formula, the Caroli formula could be easily recovered and a
      transmission coefficient formula for interface problem in the ballistic system
      can be obtained. The condition of validity for the formula is carefully explored.
      We mainly focus on heat transport. However, the corresponding electrical
      transport could be similarly dealt with. Also, an illustrative example is given
      to clarify the precise meaning of the quantities used in the formula, such as the
      concept of the reduced interacting matrix in different situations. In addition,
      an explicit transmission coefficient formula for a general one-dimensional
      interface setup is obtained based on the derived interface formula.

PMID- 23005403
TI  - From closed to open one-dimensional Anderson model: transport versus spectral
      statistics.
AB  - Using the phenomenological expression for the level spacing distribution with
      only one parameter 0 <= beta <= infinity covering all regimes of chaos and
      complexity in a quantum system, we show that transport properties of the one
      dimensional Anderson model of finite size can be expressed in terms of this
      parameter. Specifically, we demonstrate a strictly linear relation between beta
      and the normalized localization length for the whole transition from strongly
      localized to extended states. This result allows one to describe all transport
      properties in the open system entirely in terms of the parameter beta and the
      strength of the coupling to the continuum. For nonperfect coupling, our data show
      a quite unusual interplay between the degree of internal chaos defined by beta
      and the degree of openness of the model. The results can be experimentally tested
      in single-mode waveguides with either bulk or surface disorder.

PMID- 23005404
TI  - Negative thermophoresis of nanoparticles in the free molecular regime.
AB  - Negative thermophoresis is a phenomenon of particle transport induced by a
      temperature gradient, by which small particles migrate from low to high
      temperatures. In gas media, it depends strongly on the gas-particle interaction
      and temperature. In this paper, we show that negative thermophoresis is possible
      in the free molecular regime and a theoretical criterion is derived. On the basis
      of a general gas-particle interaction potential, an empirical necessary condition
      for negative thermophoresis that the potential parameters should satisfy is also
      obtained. Finally, the temperature ranges for the occurrence of negative
      thermophoresis are determined for a series of gas-particle interaction
      parameters.

PMID- 23005405
TI  - Shear flow of dense granular materials near smooth walls. I. Shear localization
      and constitutive laws in the boundary region.
AB  - We report on a numerical study of the shear flow of a simple two-dimensional
      model of a granular material under controlled normal stress between two parallel
      smooth frictional walls moving with opposite velocities +/- V. Discrete
      simulations, which are carried out with the contact dynamics method in dense
      assemblies of disks, reveal that, unlike rough walls made of strands of
      particles, smooth ones can lead to shear strain localization in the boundary
      layer. Specifically, we observe, for decreasing V, first a fluidlike regime (A),
      in which the whole granular layer is sheared, with a homogeneous strain rate
      except near the walls, then (B) a symmetric velocity profile with a solid block
      in the middle and strain localized near the walls, and finally (C) a state with
      broken symmetry in which the shear rate is confined to one boundary layer, while
      the bulk of the material moves together with the opposite wall. Both transitions
      are independent of system size and occur for specific values of V. Transient
      times are discussed. We show that the first transition, between regimes A and B,
      can be deduced from constitutive laws identified for the bulk material and the
      boundary layer, while the second one could be associated with an instability in
      the behavior of the boundary layer. The boundary zone constitutive law, however,
      is observed to depend on the state of the bulk material nearby.

PMID- 23005406
TI  - Shear flow of dense granular materials near smooth walls. II. Block formation and
      suppression of slip by rolling friction.
AB  - The role of rotational degrees of freedom and of microscopic contact properties
      at smooth walls in two dimensional planar shear has been investigated by contact
      dynamics simulations of round hard frictional particles. Our default system setup
      consists of smooth frictional walls, giving rise to slip. We show that there
      exists a critical microscopic friction coefficient at the walls, above which they
      are able to shear the granular medium. We observe distinctive features at this
      critical point, which to our knowledge have not been reported before. Activating
      rolling friction at smooth walls reduces slip, leading to similar shear behavior
      as for rough walls (with particles glued on their surface). Our simulations with
      rough walls are in agreement with previous results, provided the roughness is
      strong enough. In the limit of small roughness amplitude, however, the
      distinctive features of shearing with smooth walls are confirmed.

PMID- 23005407
TI  - Coefficient of restitution for wet particles.
AB  - The influence of a liquid film on the coefficient of restitution (COR) is
      investigated experimentally by tracing freely falling particles bouncing on a wet
      surface. The dependence of the COR on the impact velocity and various properties
      of the particle and liquid is presented and discussed in terms of dimensionless
      numbers that characterize the interplay between inertial, viscous, and surface
      forces. In the Reynolds number regime where lubrication theory does not apply,
      the ratio of the film thickness to the particle size is found to be a crucial
      parameter determining the COR.

PMID- 23005408
TI  - Parameters and scalings for dry and immersed granular flowing layers in rotating
      tumblers.
AB  - The scaling properties of the continuous flowing layer in a quasi-2D circular
      tumbler half filled with a granular material are studied experimentally in the
      presence of three different interstitial fluids (air, water, and glycerine). In
      the dry case, the dimensionless flowing layer thickness delta(0)/d scales with
      the dimensionless flow rate Q(dry)(*) = Q/(dsqrt[gd]), where Q is the flow rate,
      d is the particle diameter, and g is the acceleration due to gravity, in
      agreement with previous studies. However, unlike previous studies, we show that
      the exponent for the power-law relation between the two depends on the range of
      Q(dry)(*) Meanwhile, the angle of repose increases linearly with Q(dry)(*). In
      the immersed case, the interstitial fluid changes the relevant time scales, which
      can be accommodated by considering the fluid properties. The result is that there
      are two different expressions for the dimensionless flow rate in the immersed
      flow; one corresponding to a free fall regime for a large Stokes number, and one
      corresponding to a viscous regime at small Stokes number. On this basis, a single
      dimensionless flow rate that incorporates both buoyancy and viscous friction is
      proposed. The effect of side walls is also investigated. For dry flows and those
      immersed in water, the thickness of the flowing layer decreases while the slope
      of the free surface increases as the gap separating the walls becomes smaller.
      For immersed granular flows with glycerine as the interstitial fluid, however,
      the ratio of the thickness of the flowing layer to the bead diameter is
      independent of the distance the between the side walls because viscous effects
      dominate.

PMID- 23005409
TI  - Edwards thermodynamics of the jamming transition for frictionless packings:
      ergodicity test and role of angoricity and compactivity.
AB  - This paper illustrates how the tools of equilibrium statistical mechanics can
      help to describe a far-from-equilibrium problem: the jamming transition in
      frictionless granular materials. Edwards ideas consist of proposing a statistical
      ensemble of volume and stress fluctuations through the thermodynamic notion of
      entropy, compactivity, X, and angoricity, A (two temperature-like variables). We
      find that Edwards thermodynamics is able to describe the jamming transition (J
      point) in frictionless packings. Using the ensemble formalism we elucidate the
      following: (i) We test the combined volume-stress ensemble by comparing the
      statistical properties of jammed configurations obtained by dynamics with those
      averaged over the ensemble of minima in the potential energy landscape as a test
      of ergodicity. Agreement between both methods supports the idea of ergodicity and
      "thermalization" at a given angoricity and compactivity. (ii) A microcanonical
      ensemble analysis supports the maximum entropy principle for grains. (iii) The
      intensive variables A and X describe the approach to jamming through a series of
      scaling relations as A -> 0+ and X -> 0-. Due to the force-strain coupling in the
      interparticle forces, the jamming transition is probed thermodynamically by a
      "jamming temperature" T(J) composed of contributions from A and X. (iv) The
      thermodynamic framework reveals the order of the jamming phase transition by
      showing the absence of critical fluctuations at jamming in static observables
      like pressure and volume, and we discuss other critical scenarios for the jamming
      transition. (v) Finally, we elaborate on a comparison with relevant studies by
      Gao, Blawzdziewicz, and O'Hern [Phys. Rev. E 74, 061304 (2006)], showing a
      breakdown of equiprobability of microstates obtained via fast quenches. A network
      analysis of the energy landscape reveals the origin of the inhomogeneities in the
      uneven distribution of the areas of the basins. Such inhomogeneities are also
      found in other out-of-equilibrium systems like Lennard-Jones glasses and their
      existence does not preclude the use of statistical mechanics for jammed systems.

PMID- 23005410
TI  - Transition dynamics and magic-number-like behavior of frictional granular
      clusters.
AB  - Force chains, the primary load-bearing structures in dense granular materials,
      rearrange in response to applied stresses and strains. These self-organized grain
      columns rely on contacts from weakly stressed grains for lateral support to
      maintain and find new stable states. However, the dynamics associated with the
      regulation of the topology of contacts and strong versus weak forces through such
      contacts remains unclear. This study of local self-organization of frictional
      particles in a deforming dense granular material exploits a transition matrix to
      quantify preferred conformations and the most likely conformational transitions.
      It reveals that favored cluster conformations reside in distinct stability
      states, reminiscent of "magic numbers" for molecular clusters. To support axial
      loads, force chains typically reside in more stable states of the stability
      landscape, preferring stabilizing trusslike, three-cycle contact triangular
      topologies with neighboring grains. The most likely conformational transitions
      during force chain failure by buckling correspond to rearrangements among, or
      loss of, contacts which break the three-cycle topology.

PMID- 23005411
TI  - Energy transport velocity in bidispersed magnetic colloids.
AB  - Study of energy transport velocity of light is an effective background for slow,
      fast, and diffuse light and exhibits the photonic property of the material. We
      report a theoretical analysis of magnetic field dependent resonant behavior in
      forward-backward anisotropy factor, light diffusion constant, and energy
      transport velocity for bidispersed magnetic colloids. A bidispersed magnetic
      colloid is composed of micrometer size magnetic spheres dispersed in a magnetic
      nanofluid consisting of magnetic nanoparticles in a nonmagnetic liquid carrier.
      Magnetic Mie resonances and reduction in energy transport velocity accounts for
      the possible delay (longer dwell time) by field dependent resonant light
      transport. This resonant behavior of light in bidispersed magnetic colloids
      suggests a novel magnetophotonic material.

PMID- 23005412
TI  - Nonequilibrium condensation and coarsening of field-driven dipolar colloids.
AB  - In colloidal suspensions, self-organization processes can be easily fueled by
      external fields. Here we consider monolayers of particles with permanent dipole
      moments that are driven by rotating external fields. In recent experiments, it
      has been shown that the particles in such systems self-organize into two
      dimensional clusters. Here we report results from a computer simulation study of
      these pattern forming systems. Specifically, we employ Langevin dynamics
      simulations, Brownian dynamics simulations that include hydrodynamic
      interactions, and Wang-Landau Monte Carlo simulations of soft spheres interacting
      via dipolar potentials. We investigate at which field strengths and frequencies
      clusters form and explore the influence of hydrodynamic interactions. We also
      examine the phase behavior of the equilibrium system resulting from a time
      average of the colloidal interactions in the rotating field. In this way we
      demonstrate that the clustering described in the driven system arises from a
      first-order phase transition between a vapor and a condensed phase.

PMID- 23005413
TI  - Brownian dynamics and dynamic Monte Carlo simulations of isotropic and liquid
      crystal phases of anisotropic colloidal particles: a comparative study.
AB  - We report on the diffusion of purely repulsive and freely rotating colloidal rods
      in the isotropic, nematic, and smectic liquid crystal phases to probe the
      agreement between Brownian and Monte Carlo dynamics under the most general
      conditions. By properly rescaling the Monte Carlo time step, being related to any
      elementary move via the corresponding self-diffusion coefficient, with the
      acceptance rate of simultaneous trial displacements and rotations, we demonstrate
      the existence of a unique Monte Carlo time scale that allows for a direct
      comparison between Monte Carlo and Brownian dynamics simulations. To estimate the
      validity of our theoretical approach, we compare the mean square displacement of
      rods, their orientational autocorrelation function, and the self-intermediate
      scattering function, as obtained from Brownian dynamics and Monte Carlo
      simulations. The agreement between the results of these two approaches, even
      under the condition of heterogeneous dynamics generally observed in liquid
      crystalline phases, is excellent.

PMID- 23005414
TI  - Haloing in bimodal magnetic colloids: the role of field-induced phase separation.
AB  - If a suspension of magnetic micrometer-sized and nanosized particles is subjected
      to a homogeneous magnetic field, the nanoparticles are attracted to the
      microparticles and form thick anisotropic halos (clouds) around them. Such clouds
      can hinder the approach of microparticles and result in effective repulsion
      between them [M. T. Lopez-Lopez, A. Yu. Zubarev, and G. Bossis, Soft Matter 6,
      4346 (2010)]. In this paper, we present detailed experimental and theoretical
      studies of nanoparticle concentration profiles and of the equilibrium shapes of
      nanoparticle clouds around a single magnetized microsphere, taking into account
      interactions between nanoparticles. We show that at a strong enough magnetic
      field, the ensemble of nanoparticles experiences a gas-liquid phase transition
      such that a dense liquid phase is condensed around the magnetic poles of a
      microsphere while a dilute gas phase occupies the rest of the suspension volume.
      Nanoparticle accumulation around a microsphere is governed by two dimensionless
      parameters--the initial nanoparticle concentration (phi(0)) and the magnetic-to
      thermal energy ratio (alpha)--and the three accumulation regimes are mapped onto
      a alpha-phi(0) phase diagram. Our local thermodynamic equilibrium approach gives
      a semiquantitative agreement with the experiments on the equilibrium shapes of
      nanoparticle clouds. The results of this work could be useful for the development
      of the bimodal magnetorheological fluids and of the magnetic separation
      technologies used in bioanalysis and water purification systems.

PMID- 23005415
TI  - Spinodal fractionation in a polydisperse square-well fluid.
AB  - Using kinetic Monte Carlo simulation, we model gas-liquid spinodal decomposition
      in a size-polydisperse square well fluid, representing a "near-monodisperse"
      colloidal dispersion. We find that fractionation (demixing) of particle sizes
      between the phases begins asserting itself shortly after the onset of phase
      ordering. Strikingly, the direction of size fractionation can be reversed by a
      seemingly trivial choice between two interparticle potentials which, in the
      monodisperse case, are identical--we rationalize this in terms of a perturbative,
      equilibrium theory of polydispersity. Furthermore, our quantitative results show
      that kinetic Monte Carlo simulation can provide detailed insight into the role of
      fractionation in real colloidal systems.

PMID- 23005416
TI  - Asymptotic analysis of mode-coupling theory of active nonlinear microrheology.
AB  - We discuss a schematic model of mode-coupling theory for force-driven active
      nonlinear microrheology, where a single probe particle is pulled by a constant
      external force through a dense host medium. The model exhibits both a glass
      transition for the host and a force-induced delocalization transition, where an
      initially localized probe inside the glassy host attains a nonvanishing steady
      state velocity by locally melting the glass. Asymptotic expressions for the
      transient density correlation functions of the schematic model are derived, valid
      close to the transition points. There appear several nontrivial time scales
      relevant for the decay laws of the correlators. For the nonlinear friction
      coefficient of the probe, the asymptotic expressions cause various regimes of
      power-law variation with the external force, and two-parameter scaling laws.

PMID- 23005417
TI  - Attracted diffusion-limited aggregation.
AB  - In this paper we present results of extensive Monte Carlo simulations of
      diffusion-limited aggregation (DLA) with a seed placed on an attractive plane as
      a simple model in connection with the electrical double layers. We compute the
      fractal dimension of the aggregated patterns as a function of the attraction
      strength alpha. For the patterns grown in both two and three dimensions, the
      fractal dimension shows a significant dependence on the attraction strength for
      small values of alpha and approaches that of the ordinary two-dimensional (2D)
      DLA in the limit of large alpha. For the nonattracting case with alpha = 1, our
      results in three dimensions reproduce the patterns of 3D ordinary DLA, while in
      two dimensions our model leads to the formation of a compact cluster with
      dimension 2. For intermediate alpha, the 3D clusters have a quasi-2D structure
      with a fractal dimension very close to that of the ordinary 2D DLA. This allows
      one to control the morphology of a growing cluster by tuning a single external
      parameter alpha.

PMID- 23005418
TI  - Hydrodynamic interaction between two vesicles in a linear shear flow: asymptotic
      study.
AB  - Interactions between two vesicles in an imposed linear shear flow are studied
      theoretically, in the limit of almost spherical vesicles, with a large
      intervesicle distance, in a strong flow, with a large inner to outer viscosity
      ratio. This allows to derive a system of ordinary equations describing the
      dynamics of the two vesicles. We provide an analytic expression for the
      interaction law. We find that when the vesicles are in the same shear plane, the
      hydrodynamic interaction leads to a repulsion. When they are not, the interaction
      may turn into attraction instead. The interaction law is discussed and analyzed
      as a function of relevant parameters.

PMID- 23005419
TI  - Splinelike interpolation in particle tracking microrheology.
AB  - Converting time dependent creep compliance to frequency dependent complex shear
      modulus is an important step in analyzing the results of particle tracking
      microrheology. Fitting a function to the whole time range and transforming it to
      calculate the shear modulus is one way of solving this problem. However, the
      creep compliance of many samples, such as gels of biopolymers, shows different
      trends under different time regimes. Fitting in these regimes segmentwise results
      in a function which usually cannot be transformed in a closed analytical form. In
      general, unlike for beta and cubic splines, also the continuity of the first
      derivative cannot be ensured. In this paper, we present a method for using
      segmentwise fitting and numerical conversion, discussing interpolation for
      improving the transition between the fitted ranges, and propose a dynamic
      sampling technique to control the accuracy of the resultant complex shear
      modulus.

PMID- 23005420
TI  - Glass dynamics at high strain rates.
AB  - We present a shear-transformation-zone (STZ) theoretical analysis of molecular
      dynamics simulations of a rapidly sheared metallic glass. These simulations are
      especially revealing because, although they are limited to high strain rates,
      they span temperatures ranging from well below to well above the glass
      transition. With one important discrepancy, the simplified STZ theory used here
      reproduces the simulation data, including the way in which those data can be made
      to collapse approximately onto simple curves by a scaling transformation. The STZ
      analysis implies that the system's behavior at high strain rates is controlled
      primarily by effective-temperature thermodynamics, as opposed to system-specific
      details of the molecular interactions. The discrepancy between theory and
      simulations occurs at the lower strain rates for temperatures near the glass
      transition. We argue that this discrepancy can be resolved by the same
      multispecies generalization of STZ theory that has been proposed recently for
      understanding frequency-dependent viscoelastic responses, Stokes-Einstein
      violations, and stretched-exponential relaxation in equilibrated glassy
      materials.

PMID- 23005421
TI  - Isoviscosity lines and the liquid-glass transition in simple liquids.
AB  - This article presents the study of the generic behavior of viscosity of liquids
      based on some simple theoretical models, the soft-spheres and Lennard-Jones
      systems. The use of these simple models allows us to investigate in detail the
      viscosity behavior in a wide range of temperatures and pressures including the
      high-temperature-high-pressure limits. Based on the simulation results, we
      discuss the shape of isoviscosity lines and analyze the glass transition at high
      temperatures and high pressures. Despite the fact that the viscosity drastically
      increases in the limit of high temperatures and high pressures along the melting
      line, the relaxation time rapidly decreases in this region, and the system
      becomes further from the glass transition.

PMID- 23005422
TI  - Glassy dynamics in a confined monatomic fluid.
AB  - Molecular dynamic simulations of a strongly inhomogeneous system reveals that a
      single-component soft-sphere fluid can behave as a fragile glass former due to
      confinement. The self-intermediate scattering function, F(s)(k,t), of a Lennard
      Jones fluid confined in slit-shaped pores, which can accommodate two to four
      fluid layers, exhibits a two-step relaxation at moderate temperatures. The mean
      squared displacement data are found to follow time-temperature superposition and
      both the self-diffusivity and late alpha relaxation times exhibit power-law
      divergences as the fluid is cooled. The system possesses a crossover temperature
      and follows the scalings of mode coupling theory for the glass transition. The
      temperature dependence of the self-diffusivity can be expressed using the Vogel
      Fulcher-Tammann equation, and estimates of the fragility index of the system
      indicates a fragile glass former. At lower temperatures, signatures of additional
      relaxation processes are observed in the various dynamical quantities with a
      three-step relaxation observed in the F(s)(k,t).

PMID- 23005423
TI  - Seebeck effect in electrolytes.
AB  - We study Seebeck effect in liquid electrolytes, starting from its simple neutral
      analog--thermodiffusion (so-called Ludwig-Soret or Soret effect). It is observed
      that when two or more subsystems of mobile particles are subjected to the
      temperature gradient, various types of them respond to it differently. In the
      case when these fractions, with different mobility parameters (Soret
      coefficients), are oppositely charged (a case typical for electrolytes), the
      nonhomogeneous internal electric field is generated. The latter field prevents
      these fractions from space separation and determines the intensity of the
      appearing Seebeck effect.

PMID- 23005424
TI  - Many-particle surface diffusion coefficients near first-order phase transitions
      at low temperatures.
AB  - We analyze the chemical and jump surface diffusion coefficients, D(c) and D(J),
      near a first-order phase transition at which two phases coexist and the surface
      coverage, theta, jumps between single-phase values theta(-)(*) and theta(+)(*).
      Contrary to other studies, we consider temperatures that are sufficiently
      subcritical. Using the local equilibrium approximation, we obtain approximate
      analytical formulas for the dependences of D(c) and D(J) on the coverage and
      system size, N, near such a transition. In the two-phase regime, when theta
      ranges between theta-* and theta+*, the diffusion coefficients behave as the sums
      of two hyperbolas, D(c) ~ A-/N|theta-theta(-)(*)| + A+/N|theta-theta(+)(*)| and
      D(J) ~ A(-)|theta-theta(+)(*)|/theta+A(+)|theta-theta(-)(*)|/theta. This behavior
      rapidly changes as the system goes from the two-phase regime to either of the
      single-phase regimes (when theta goes below theta(-)(*) or above theta(+)(*)).
      The crossover behavior of D(c)(theta) and D(J)(theta) between the two-phase and
      single-phase regimes is described by rather complex formulas involving the
      Lambert function. We consider a lattice-gas model on a triangular lattice to
      illustrate these general results, applying them to four specific examples of
      transitions exhibited by the model.

PMID- 23005425
TI  - Spectral properties of thermal fluctuations on simple liquid surfaces below shot
      noise levels.
AB  - We study the spectral properties of thermal fluctuations on simple liquid
      surfaces, sometimes called ripplons. Analytical properties of the spectral
      function are investigated and are shown to be composed of regions with simple
      analytic behavior with respect to the frequency or the wave number. The derived
      expressions are compared to spectral measurements performed orders of magnitude
      below shot-noise levels, which is achieved using a novel noise reduction method.
      The agreement between the theory of thermal surface fluctuations and the
      experiment is found to be excellent, elucidating the spectral properties of the
      surface fluctuations. The measurement method requires relatively only a small
      sample both spatially (few MUm) and temporally (~20 s). The method also requires
      relatively weak light power (~0.5 mW) so that it has a broad range of
      applicability, including local measurements, investigations of time-dependent
      phenomena, and noninvasive measurements.

PMID- 23005426
TI  - Wenzel and Cassie-Baxter states of an electrolytic drop on charged surfaces.
AB  - In this paper, we provide a theory for the Wenzel and the Cassie-Baxter states of
      an electrolyte drop on charged surfaces. An electric double layer (EDL) develops
      when the electrolyte drop comes in contact with the charged surface. Therefore,
      the EDL free energy affects these states by triggering a hydrophilicity-inducing
      tendency. Consequently, an originally hydrophilic condition leads to a
      superhydrophilic Wenzel state, and an originally hydrophobic condition leads to a
      less hydrophobic Wenzel state. For the Cassie-Baxter state, this gives rise to
      the most remarkable situation of a hydrophilic (as compared to the original)
      Cassie-Baxter state.

PMID- 23005427
TI  - Numerical computations of faceted pattern formation in snow crystal growth.
AB  - Faceted growth of snow crystals leads to a rich diversity of forms with
      remarkable sixfold symmetry. Snow crystal structures result from diffusion
      limited crystal growth in the presence of anisotropic surface energy and
      anisotropic attachment kinetics. It is by now well understood that the
      morphological stability of ice crystals strongly depends on supersaturation,
      crystal size, and temperature. Until very recently it was very difficult to
      perform numerical simulations of this highly anisotropic crystal growth. In
      particular, obtaining facet growth in combination with dendritic branching is a
      challenging task. We present numerical simulations of snow crystal growth in two
      and three spacial dimensions using a computational method recently introduced by
      the present authors. We present both qualitative and quantitative computations.
      In particular, a linear relationship between tip velocity and supersaturation is
      observed. In our computations, surface energy effects, although small, have a
      pronounced effect on crystal growth. We compute solid plates, solid prisms,
      hollow columns, needles, dendrites, capped columns, and scrolls on plates.
      Although all these forms appear in nature, it is a significant challenge to
      reproduce them with the help of numerical simulations for a continuum model.

PMID- 23005428
TI  - Multiple interfaces in diffusional phase transitions in binary mesogen-nonmesogen
      mixtures undergoing metastable phase separations.
AB  - Theory and simulations of simultaneous chemical demixing and phase ordering are
      performed for a mixed order parameter system with an isotropic-isotropic (I-I)
      phase separation that is metastable with respect to an isotropic-nematic (I-N)
      phase-ordering transition. Under certain conditions, the disordered phase
      transforms into an ordered phase via the motion of a double front containing a
      metastable phase produced by I-I demixing, a thermodynamically driven mechanism
      not previously reported. Different kinetic regimes are found depending on the
      location of the initial conditions in the thermodynamic phase diagram and the
      ratio between diffusional and nematic phase-ordering mobilities. For a
      diffusional process, depending if the temperature is above or below the critical
      codissolution point, an inflection point or a phase separation takes place in the
      depletion layer. This phase separation leads to the formation of a second
      interface where the separation of the two metastable isotropic phases grows
      monotonically with time. The observed deviations from the typical Fickian
      concentration profiles are associated with strong positive deviations of the
      mixture from ideality due to couplings between concentration and nematic
      ordering. Although systems of interest include liquid-crystalline nanocomposites,
      this mechanism may apply to any mixture that can undergo an order-disorder
      transition and demix.

PMID- 23005429
TI  - Molecular shape and the energetics of chemisorption: from simple to complex
      energy landscapes.
AB  - We enumerate all local minima of the energy landscape for model rigid adsorbates
      characterized by three or four equivalent binding sites (e.g., thiol groups) on a
      close-packed (111) surface of a face-centered-cubic crystal. We show that the
      number of energy minima increases linearly with molecular size with a rate of
      increase that depends on the degree of registry between the molecule shape and
      the surface structure. The sparseness of energy minima and the large variations
      in the center-of-mass positions of these minima vs molecular size for molecules
      that are incommensurate with the surface suggests a strong coupling in these
      molecules between surface mobility and shape or size fluctuations resulting from
      molecular vibrations. We also find that the variation in the binding energy with
      respect to molecular size decreases more rapidly with molecular size for
      molecules with a higher degree of registry with the surface. This indicates that
      surface adsorption should be better able to distinguish molecules by size if the
      molecules are incommensurate with the surface.

PMID- 23005430
TI  - Droplet spreading and pinning on heterogeneous substrates.
AB  - The contact angle of a fluid droplet on an heterogeneous surface is analyzed
      using the statistical dynamics of the spreading contact line. The statistical
      properties of the final droplet radius and contact angle are obtained through
      applications of depinning transitions of contact lines with nonlocal elasticity
      and features of pinning-depinning dynamics. Such properties not only depend on
      disorder strength and surface details, but also on the droplet volume and
      disorder correlation length. Deviations from Wenzel or Cassie-Baxter behavior are
      particularly apparent in the case of small droplet volumes and small contact
      angles.

PMID- 23005431
TI  - Director fluctuations in nematic liquid crystals induced by an ultrasonic wave.
AB  - The director-density coupling theory was formulated with two parameters (u(1) and
      u(2)) to explain the acousto-optic effect in nematic liquid crystals. The
      assumption that the director is not able to accompany rapid oscillations of the
      sound wave, so that it actually couples to the time-averaged interaction, renders
      it effectively a u(1)-independent theory. In this paper, we investigate a route
      in which the time average is postponed to the end of the calculation. This
      approach allows us to derive measurable quantities that depend on both u(1) and
      u(2).

PMID- 23005432
TI  - Splay and bend disclinations in multidomain vertical-alignment liquid-crystal
      cells.
AB  - We investigated the domain boundary formations in multidomain vertical-alignment
      nematic liquid-crystal (VA LC) cells. There are two types of domain boundaries in
      multidomain VA cells, splay and bend type domains, the boundaries of which are
      dominated by the splay and bend deformations, respectively. Each type could be
      achieved by either the single-4-domain pair or the 2-2-domain pair of two
      substrates and have four different domain arrangements. We demonstrated that the
      disclination width of the splay type domain is about 50% wider than that of the
      bend type domain even when the splay and bend elastic constants are the same. The
      difference is so large that it cannot be compensated for by adjusting the elastic
      constants of the LCs within realistic material parameter ranges. The mechanism of
      the phenomenon was investigated by disassembling the elastic deformation strains
      into each component and analyzing them individually. The large difference was
      revealed to arise from the different twist deformation strains near the surface,
      which is significantly larger in the bend type than in the splay type. We also
      suggest an asymmetric pretilt structure, which dramatically reduces the domain
      boundary width. However, simple adoption of a large pretilt angle is not
      effective for reducing the width. The experimental results obtained in real LC
      display panels qualitatively agree well with the simulation results.

PMID- 23005433
TI  - Nematic wetting and filling of crenellated surfaces.
AB  - We investigate nematic wetting and filling transitions of crenellated surfaces
      (rectangular gratings) by numerical minimization of the Landau-de Gennes free
      energy as a function of the anchoring strength, for a wide range of the surface
      geometrical parameters: depth, width, and separation of the crenels. We have
      found a rich phase behavior that depends in detail on the combination of the
      surface parameters. By comparison to simple fluids, which undergo a continuous
      filling or unbending transition, where the surface changes from a dry to a filled
      state, followed by a wetting or unbinding transition, where the thickness of the
      adsorbed fluid becomes macroscopic and the interface unbinds from the surface,
      nematics at crenellated surfaces reveal an intriguingly rich behavior: in shallow
      crenels only wetting is observed, while in deep crenels, only filling transitions
      occur; for intermediate surface geometrical parameters, a new class of filled
      states is found, characterized by bent isotropic-nematic interfaces, which
      persist for surfaces structured on large scales, compared to the nematic
      correlation length. The global phase diagram displays two wet and four filled
      states, all separated by first-order transitions. For crenels in the intermediate
      regime re-entrant filling transitions driven by the anchoring strength are
      observed.

PMID- 23005434
TI  - Tetrahedratic mesophases, chiral order, and helical domains induced by
      quadrupolar and octupolar interactions.
AB  - We present an exhaustive account of phases and phase transitions that can be
      stabilized in the recently introduced generalized Lebwohl-Lasher model with
      quadrupolar and octupolar microscopic interactions [L. Longa, G. Pajak, and T.
      Wydro, Phys. Rev. E 79, 040701(R) (2009)]. A complete mean-field analysis of the
      model, along with Monte Carlo simulations allows us to identify four distinct
      classes of the phase diagrams with a number of multicritical points where, in
      addition to the standard uniaxial and biaxial nematic phases, the other nematic
      like phases are stabilized. These involve, among the others, tetrahedratic (T),
      nematic tetrahedratic (N(T)), and chiral nematic tetrahedratic (N(T)(*)) phases
      of global T(d), D(2d), and D(2) symmetry, respectively. Molecular order
      parameters and correlation functions in these phases are determined. We conclude
      with generalizations of the model that give a simple molecular interpretation of
      macroscopic regions with opposite optical activity (ambidextrous chirality),
      observed, e.g., in bent-core systems. An estimate of the helical pitch in the
      N(T)(*) phase is also given.

PMID- 23005435
TI  - Density of photon states in dye-doped chiral nematic liquid crystal cells in the
      presence of losses and gain.
AB  - We calculate the density of photon states (DOS) of the normal modes in dye-doped
      chiral nematic liquid crystal (LC) cells in the presence of various loss
      mechanisms. Losses and gain are incorporated into the transmission
      characteristics through the introduction of a small imaginary part in the
      dielectric constant perpendicular and along the director, for which we assume no
      frequency dispersion. Theoretical results are presented on the DOS in the region
      of the photonic band gap for a range of values of the loss coefficient and
      different values of the optical anisotropy. The obtained values of the DOS at the
      photonic band gap edges predict a reversal of the dominant modes in the
      structure. Our results are found to be in good agreement with the experimentally
      obtained excitation thresholds in chiral nematic LC lasers. The behavior of the
      DOS is also discussed for amplifying LC cells providing additional insight to the
      lasing mechanism of these structures.

PMID- 23005436
TI  - Photoinduced reordering in thin azo-dye films and light-induced reorientation
      dynamics of the nematic liquid-crystal easy axis.
AB  - We theoretically study the kinetics of photoinduced reordering triggered by
      linearly polarized (LP) reorienting light in thin azo-dye films that were
      initially illuminated with LP ultraviolet pumping beam. The process of reordering
      is treated as a rotational diffusion of molecules in the light intensity
      dependent mean-field potential. The two-dimensional diffusion model which is
      based on the free energy rotational Fokker-Planck equation and describes the
      regime of in-plane reorientation is generalized to analyze the dynamics of the
      azo-dye order parameter tensor at varying polarization azimuth of the reorienting
      light. It is found that, in the photosteady state, the intensity of LP
      reorienting light determines the scalar order parameter (the largest eigenvalue
      of the order parameter tensor), whereas the steady state orientation of the
      corresponding eigenvector (the in-plane principal axis) depends solely on the
      polarization azimuth. We show that, under certain conditions, reorientation takes
      place only if the reorienting light intensity exceeds its critical value. Such
      threshold behavior is predicted to occur in the bistability region provided that
      the initial principal axis lies in the polarization plane of reorienting light.
      The model is used to interpret the experimental data on the light-induced
      azimuthal gliding of the liquid-crystal easy axis on photoaligned azo-dye
      substrates.

PMID- 23005437
TI  - Breaking the rules for topological defects: smectic order on conical substrates.
AB  - Ordered phases on curved substrates experience a complex interplay of ordering
      and intrinsic curvature, commonly producing frustration and singularities. This
      is an especially important issue in crystals as ever-smaller scale materials are
      grown on real surfaces; eventually, surface imperfections are on the same scale
      as the lattice constant. Here, we gain insights into this general problem by
      studying two-dimensional smectic order on substrates with highly localized
      intrinsic curvature, constructed from cones and their intersections with planes.
      In doing so we take advantage of fully tractable "paper and tape" constructions,
      allowing us to understand, in detail, the induced cusps and singularities.

PMID- 23005438
TI  - Light scattering from liquid crystal director fluctuations in steady magnetic
      fields up to 25 tesla.
AB  - We report on homodyne dynamic light scattering measurements of orientational
      fluctuation modes in both calamitic and bent-core nematic liquid crystals,
      carried out in the new split-helix resistive magnet at the National High Magnetic
      Field Laboratory. The relaxation rate and inverse scattered intensity of director
      fluctuations exhibit a linear dependence on field-squared up to 25 tesla, which
      is consistent with strictly lowest order coupling of the tensor order parameter Q
      to field (Q(alphabeta)B(alpha)B(beta)) in the nematic free energy. However, we
      also observe evidence of field dependence of certain nematic material parameters,
      an effect which may be expected from the mean field scaling of these quantities
      with the magnitude of Q and the predicted variation of Q with field.

PMID- 23005439
TI  - Nematic liquid crystals on spherical surfaces: control of defect configurations
      by temperature, density, and rod shape.
AB  - Recent experiments have shown that defect conformations in spherical nematic
      liquid crystals can be controlled through variations of temperature, shell
      thickness, and other environmental parameters. These modifications can be
      understood as a result of the induced changes in the effective elastic constants
      of the system. To characterize the relation between defect conformations and
      elastic anisotropy, we carry out Monte Carlo simulations of a nematic on a
      spherical surface. As the anisotropy is increased, the defects flow from a
      tetrahedral arrangement to two coalescing pairs and then to a great circle
      configuration. We also analyze this flow using a variational method based on
      harmonic configurations.

PMID- 23005440
TI  - Rheological properties of a reentrant nematic liquid crystal.
AB  - We report experimental studies on small angle light scattering (SALS), and
      rheodielectric and electrorheological properties of a binary mixture of octyloxy
      cyanobiphenyl and hexyloxy cyanobiphenyl liquid crystals. The mixture exhibits
      nematic (N) to smectic-A (SmA) phase transitions, and then again to a reentrant
      nematic (N(R)) phase transition. Rapid shear thinning in the quenched samples in
      the low shear rate region in the N and SmA phases observed from SALS experiments
      is attributed to the realignment of the director within the domains. The domains
      are elongated along the shear direction at higher shear rates. The temperature
      variation of the effective viscosity and static dielectric constant reveals the
      changes in the director orientation across N-SmA-N(R) phase transitions. At a
      steady shear rate the effective viscosity increases with the electric field in
      all the phases and saturates at much higher fields. It also exhibits two
      anomalous peaks across N-SmA-N(R) phase transitions beyond a particular field.
      The shear modulus of the SmA phase in an intermediate field is significantly
      larger than that measured at both low and high fields. This enhanced
      viscoelasticity of the SmA phase is argued to originate from the increased
      dislocation density.

PMID- 23005441
TI  - Surface topography and rotational symmetry breaking.
AB  - The surface electroclinic effect, which is a rotation of the molecular director
      in the substrate plane proportional to an electric field E applied normal to the
      substrate, requires both a chiral environment and C(2) (or lower) rotational
      symmetry about E. The two symmetries typically are created in tandem by
      manipulating the surface topography, a process that conflates their effects. Here
      we use a pair of rubbed polymer-coated substrates in a twist geometry to obtain
      our main result, viz., that the strengths of two symmetries, in this case the rub
      induced breaking of C(infinity) rotational symmetry and chiral symmetry, can be
      separated and quantified. Experimentally we observe that the strength of the
      reduced rotational symmetry arising from the rub-induced scratches, which is
      proportional to the electroclinic response, scales linearly with the induced
      topographical rms roughness and increases with increasing rubbing strength of the
      polymer. Our results also suggest that the azimuthal anchoring strength
      coefficient is relatively insensitive to the strength of the rubbing.

PMID- 23005442
TI  - Solution parameters for the fabrication of thinner silicone fibers by
      electrospinning.
AB  - Silicone fibers were synthesized by electrospinning, where 17 solvents with
      different chemical properties (boiling point, conductivity, viscosity, dielectric
      constant, and solubility parameter) were used to dissolve the silicone polymer
      for the formation of fibers through electrospinning. Previous reports on the
      miniaturization of fibers of polymers dissolved in a solvent suggested that the
      low viscosity and the high conductivity of the polymer solution were the key
      parameters to form thinner fibers when using a single solvent. Here we have found
      a powerful way to search for good solvents to reduce the fiber diameters as well
      as to dissolve the polymers. By considering different types of solvents, it was
      found that the solubility parameters conclusively determined the smallest fiber
      diameters of the silicone polymers. The solubility parameter of the silicone
      polymer should be lower than those of the solvents to make thinner fibers. The
      results have revealed the strong relationship between the diameters of the fibers
      and the solubility parameters of the solvents, and they indicate that the
      solubility parameter could be a good indicative parameter in selecting solvents
      during the fabrication of thinner fibers by electrospinning, especially for
      siloxane polymers.

PMID- 23005443
TI  - Exact partition function zeros of a polymer on a simple cubic lattice.
AB  - We study conformational transitions of a polymer on a simple-cubic lattice by
      calculating the zeros of the exact partition function, up to chain length 24. In
      the complex temperature plane, two loci of the partition function zeros are found
      for longer chains, suggesting the existence of both the coil-globule collapse
      transition and the melting-freezing transition. The locus corresponding to coil
      globule transition clearly approaches the real axis as the chain length
      increases, and the transition temperature could be estimated by finite-size
      scaling. The form of the logarithmic correction to the scaling of the partition
      function zeros could also be obtained. The other locus does not show clear
      scaling behavior, but a supplementary analysis of the specific heat reveals a
      first-order-like pseudotransition.

PMID- 23005444
TI  - Propagation of tension along a polymer chain.
AB  - We study the propagation of tension caused by an external force along a long
      polymeric molecule in two different settings, namely along a free polymer in
      three-dimensional (3D) space being pulled from one end, and along a prestretched
      circular polymer, confined in a narrow circular tube. We show that in both cases,
      the tension propagation is governed by a diffusion equation, and in particular,
      the tension front propagates as t(1/2) along the contour of the chain. The
      results are confirmed numerically, and by molecular dynamics simulations in the
      case of the 3D polymer. We also compare our results with the previously suggested
      ones for the translocation setting, and discuss why tension propagation is slower
      in that case.

PMID- 23005445
TI  - Dragging a polymer in a viscous fluid: steady state and transient.
AB  - We study the conformation and dynamics of a single polymer chain that is pulled
      by a constant force applied at its one end with the other end free. Such a
      situation is relevant to the growing technology of manipulating individual
      macromolecules, which offers a paradigm research for probing far-from-equilibrium
      responses of long flexible biological polymers. We first analyze the Rouse model
      for the Gaussian chains for which the exact analytical results can be obtained.
      More realistic features such as the finite extensibility, the excluded volume,
      and the hydrodynamic interactions are taken into account with the help of the
      scaling argument, which leads to various nontrivial predictions such as the force
      dependent friction constants. We elucidate (i) generalized dynamical equations of
      state describing extension and friction laws in steady-state and (ii) the tension
      propagation laws in the transient process. We point out that the time evolutions
      of the dynamic friction in the transient process crucially depend on the
      experimental protocol, i.e., either constant force or constant velocity ensemble.
      These predictions could be verified in experiments using giant DNAs and
      chromosomes.

PMID- 23005446
TI  - Collective dynamics of self-propelled particles with variable speed.
AB  - Understanding the organization of collective motion in biological systems is an
      ongoing challenge. In this paper we consider a minimal model of self-propelled
      particles with variable speed. Inspired by experimental data from schooling fish,
      we introduce a power-law dependency of the speed of each particle on the degree
      of polarization order in its neighborhood. We derive analytically a coarse
      grained continuous approximation for this model and find that, while the specific
      variable speed rule used does not change the details of the ordering transition
      leading to collective motion, it induces an inverse power-law correlation between
      the speed or the local polarization order and the local density. Using numerical
      simulations, we verify the range of validity of this continuous description and
      explore regimes beyond it. We discover, in disordered states close to the
      transition, a phase-segregated regime where most particles cluster into almost
      static groups surrounded by isolated high-speed particles. We argue that the
      mechanism responsible for this regime could be present in a wide range of
      collective motion dynamics.

PMID- 23005447
TI  - Microtubules interacting with a boundary: mean length and mean first-passage
      times.
AB  - I formulate a dynamical model for microtubules interacting with a catastrophe
      inducing boundary. In this model microtubules are either waiting to be nucleated,
      actively growing or shrinking, or stalled at the boundary. I first determine the
      steady-state occupation of these various states and the resultant length
      distribution. Next, I formulate the problem of the mean first-passage time to
      reach the boundary in terms of an appropriate set of splitting probabilities and
      conditional mean first-passage times and solve explicitly for these quantities
      using a differential equation approach. As an application, I revisit a recently
      proposed search-and-capture model for the interaction between microtubules and
      target chromosomes [M. Gopalakrishnan and B. S. Govindan, Bull. Math. Biol. 73,
      2483 (2011)]. I show how my approach leads to a direct and compact solution of
      this problem.

PMID- 23005448
TI  - Controlling the formation of a monolayer of cytochrome P450 reductase onto Au
      surfaces.
AB  - The conditions necessary for the formation of a monolayer and a bilayer of a
      mutated form (P499C) of human cytochrome P450 reductase on a Au(110)/electrolyte
      interface have been determined using a quartz crystal microbalance with
      dissipation, atomic force microscopy, and reflection anisotropy spectroscopy
      (RAS). The molecules adsorb through a Au-S linkage and, for the monolayer, adopt
      an ordered structure on the Au(110) substrate in which the optical axes of the
      dipoles contributing to the RAS signal are aligned roughly along the optical axes
      of the Au(110) substrate. Differences between the absorption spectrum of the
      molecules in a solution and the RAS profile of the adsorbed monolayer are
      attributed to surface order in the orientation of dipoles that contribute in the
      low energy region of the spectrum, a roughly vertical orientation on the surface
      of the long axes of the isoalloxazine rings and the lack of any preferred
      orientation in the molecular structure of the dipoles in the aromatic amino
      acids. Our studies establish an important proof of principle for immobilizing
      large biological macromolecules to gold surfaces. This opens up detailed studies
      of the dynamics of biological macromolecules by RAS, which have general
      applications in studies of biological redox chemistry that are coupled to protein
      dynamics.

PMID- 23005449
TI  - Migration of adhesive glioma cells: front propagation and fingering.
AB  - We investigate the migration of glioma cells as a front propagation phenomenon
      both theoretically (by using both discrete lattice modeling and a continuum
      approach) and experimentally. For small effective strength of cell-cell adhesion
      q, the front velocity does not depend on q. When q exceeds a critical threshold,
      a fingeringlike front propagation is observed due to cluster formation in the
      invasive zone. We show that the experiments correspond to the transient regime,
      before the regime of front propagation is established. We performed an additional
      experiment on cell migration. A detailed comparison with experimental
      observations showed that the theory correctly predicts the maximal migration
      distance but underestimates the migration of the main mass of cells.

PMID- 23005450
TI  - Stretching DNA to quantify nonspecific protein binding.
AB  - Nonspecific binding of regulatory proteins to DNA can be an important mechanism
      for target search and storage. This seems to be the case for the lambda repressor
      protein (CI), which maintains lysogeny after infection of E. coli. CI binds
      specifically at two distant regions along the viral genome and induces the
      formation of a repressive DNA loop. However, single-molecule imaging as well as
      thermodynamic and kinetic measurements of CI-mediated looping show that CI also
      binds to DNA nonspecifically and that this mode of binding may play an important
      role in maintaining lysogeny. This paper presents a robust phenomenological
      approach using a recently developed method based on the partition function, which
      allows calculation of the number of proteins bound nonspecific to DNA from
      measurements of the DNA extension as a function of applied force. This approach
      was used to analyze several cycles of extension and relaxation of lambda DNA
      performed at several CI concentrations to measure the dissociation constant for
      nonspecific binding of CI (~100 nM), and to obtain a measurement of the induced
      DNA compaction (~10%) by CI.

PMID- 23005451
TI  - Force fluctuations impact kinetics of biomolecular systems.
AB  - A wide array of biological processes occur at rates that vary significantly with
      force. Instantaneous molecular forces fluctuate due to thermal noise and active
      processes, leading to concomitant fluctuations in biomolecular rate constants. We
      demonstrate that such fluctuations have a dramatic effect on the transition
      kinetics of force-dependent processes. As an illustrative, biologically relevant
      example, we model the pausing of eukaryotic RNA polymerase as it transcribes
      nucleosomal DNA. Incorporating force fluctuations in the model yields
      qualitatively different predictions for the pausing time scales when compared to
      behavior under the average force alone. We use our model to illustrate the broad
      range of behaviors that can arise in biomolecular processes that are susceptible
      to force fluctuations. The fluctuation time scale, which varies significantly for
      in vivo biomolecular processes, yields very different results for overall rates
      and dramatically alters the force regime of relevance to the transition. Our
      results emphasize the importance of transient high-force behavior for determining
      kinetics in the fluctuating environment of a living cell.

PMID- 23005452
TI  - Formation of antiwaves in gap-junction-coupled chains of neurons.
AB  - Using network models consisting of gap-junction-coupled Wang-Buszaki neurons, we
      demonstrate that it is possible to obtain not only synchronous activity between
      neurons but also a variety of constant phase shifts between 0 and pi. We call
      these phase shifts intermediate stable phase-locked states. These phase shifts
      can produce a large variety of wavelike activity patterns in one-dimensional
      chains and two-dimensional arrays of neurons, which can be studied by reducing
      the system of equations to a phase model. The 2pi periodic coupling functions of
      these models are characterized by prominent higher order terms in their Fourier
      expansion, which can be varied by changing model parameters. We study how the
      relative contribution of the odd and even terms affects what solutions are
      possible, the basin of attraction of those solutions, and their stability. These
      models may be applicable to the spinal central pattern generators of the dogfish
      and also to the developing neocortex of the neonatal rat.

PMID- 23005453
TI  - Constraints on the synchronization of entorhinal cortex stellate cells.
AB  - Synchronized oscillations of large numbers of central neurons are believed to be
      important for a wide variety of cognitive functions, including long-term memory
      recall and spatial navigation. It is therefore plausible that evolution has
      optimized the biophysical properties of central neurons in some way for
      synchronized oscillations to occur. Here, we use computational models to
      investigate the relationships between the presumably genetically determined
      parameters of stellate cells in layer II of the entorhinal cortex and the ability
      of coupled populations of these cells to synchronize their intrinsic
      oscillations: in particular, we calculate the time it takes circuits of two or
      three cells with initially randomly distributed phases to synchronize their
      oscillations to within one action potential width, and the metabolic energy they
      consume in doing so. For recurrent circuit topologies, we find that parameters
      giving low intrinsic firing frequencies close to those actually observed are
      strongly advantageous for both synchronization time and metabolic energy
      consumption.

PMID- 23005454
TI  - Non-normal amplification in random balanced neuronal networks.
AB  - In dynamical models of cortical networks, the recurrent connectivity can amplify
      the input given to the network in two distinct ways. One is induced by the
      presence of near-critical eigenvalues in the connectivity matrix W, producing
      large but slow activity fluctuations along the corresponding eigenvectors
      (dynamical slowing). The other relies on W not being normal, which allows the
      network activity to make large but fast excursions along specific directions.
      Here we investigate the trade-off between non-normal amplification and dynamical
      slowing in the spontaneous activity of large random neuronal networks composed of
      excitatory and inhibitory neurons. We use a Schur decomposition of W to separate
      the two amplification mechanisms. Assuming linear stochastic dynamics, we derive
      an exact expression for the expected amount of purely non-normal amplification.
      We find that amplification is very limited if dynamical slowing must be kept
      weak. We conclude that, to achieve strong transient amplification with little
      slowing, the connectivity must be structured. We show that unidirectional
      connections between neurons of the same type together with reciprocal connections
      between neurons of different types, allow for amplification already in the fast
      dynamical regime. Finally, our results also shed light on the differences between
      balanced networks in which inhibition exactly cancels excitation and those where
      inhibition dominates.

PMID- 23005455
TI  - Voltage sensing in ion channels: mesoscale simulations of biological devices.
AB  - Electrical signaling via voltage-gated ion channels depends upon the function of
      a voltage sensor (VS), identified with the S1-S4 domain in voltage-gated K(+)
      channels. Here we investigate some energetic aspects of the sliding-helix model
      of the VS using simulations based on VS charges, linear dielectrics, and whole
      body motion. Model electrostatics in voltage-clamped boundary conditions are
      solved using a boundary element method. The statistical mechanical consequences
      of the electrostatic configurational energy are computed to gain insight into the
      sliding-helix mechanism and to predict experimentally measured ensemble
      properties such as gating charge displaced by an applied voltage. Those
      consequences and ensemble properties are investigated for two alternate S4
      configurations, alpha and 3(10) helical. Both forms of VS are found to have an
      inherent electrostatic stability. Maximal charge displacement is limited by
      geometry, specifically the range of movement where S4 charges and countercharges
      overlap in the region of weak dielectric. Charge displacement responds more
      steeply to voltage in the alpha-helical than in the 3(10)-helical sensor. This
      difference is due to differences on the order of 0.1 eV in the landscapes of
      electrostatic energy. As a step toward integrating these VS models into a full
      channel model, we include a hypothetical external load in the Hamiltonian of the
      system and analyze the energetic input-output relation of the VS.

PMID- 23005456
TI  - Lattice animal model of chromosome organization.
AB  - Polymer models tied together by constraints of looping and confinement have been
      used to explain many of the observed organizational characteristics of interphase
      chromosomes. Here we introduce a simple lattice animal representation of
      interphase chromosomes that combines the features of looping and confinement
      constraints into a single framework. We show through Monte Carlo simulations that
      this model qualitatively captures both the leveling off in the spatial distance
      between genomic markers observed in fluorescent in situ hybridization experiments
      and the inverse decay in the looping probability as a function of genomic
      separation observed in chromosome conformation capture experiments. The model
      also suggests that the collapsed state of chromosomes and their segregation into
      territories with distinct looping activities might be a natural consequence of
      confinement.

PMID- 23005457
TI  - Comparison of three-dimensional poisson solution methods for particle-based
      simulation and inhomogeneous dielectrics.
AB  - Particle-based simulation represents a powerful approach to modeling physical
      systems in electronics, molecular biology, and chemical physics. Accounting for
      the interactions occurring among charged particles requires an accurate and
      efficient solution of Poisson's equation. For a system of discrete charges with
      inhomogeneous dielectrics, i.e., a system with discontinuities in the
      permittivity, the boundary element method (BEM) is frequently adopted. It
      provides the solution of Poisson's equation, accounting for polarization effects
      due to the discontinuity in the permittivity by computing the induced charges at
      the dielectric boundaries. In this framework, the total electrostatic potential
      is then found by superimposing the elemental contributions from both source and
      induced charges. In this paper, we present a comparison between two BEMs to solve
      a boundary-integral formulation of Poisson's equation, with emphasis on the BEMs'
      suitability for particle-based simulations in terms of solution accuracy and
      computation speed. The two approaches are the collocation and qualocation
      methods. Collocation is implemented following the induced-charge computation
      method of D. Boda et al. [J. Chem. Phys. 125, 034901 (2006)]. The qualocation
      method is described by J. Tausch et al. [IEEE Transactions on Computer-Aided
      Design of Integrated Circuits and Systems 20, 1398 (2001)]. These approaches are
      studied using both flat and curved surface elements to discretize the dielectric
      boundary, using two challenging test cases: a dielectric sphere embedded in a
      different dielectric medium and a toy model of an ion channel. Earlier
      comparisons of the two BEM approaches did not address curved surface elements or
      semiatomistic models of ion channels. Our results support the earlier findings
      that for flat-element calculations, qualocation is always significantly more
      accurate than collocation. On the other hand, when the dielectric boundary is
      discretized with curved surface elements, the two methods are essentially
      equivalent; i.e., they have comparable accuracies for the same number of
      elements. We find that ions in water--charges embedded in a high-dielectric
      medium--are harder to compute accurately than charges in a low-dielectric medium.

PMID- 23005458
TI  - Error correction during DNA replication.
AB  - DNA polymerase (DNAP) is a dual-purpose enzyme that plays two opposite roles in
      two different situations during DNA replication. It plays its a normal role as a
      polymerase catalyzing the elongation of a new DNA molecule by adding a monomer.
      However, it can switch to the role of an exonuclease and shorten the same DNA by
      cleavage of the last incorporated monomer from the nascent DNA. Just as
      misincorporated nucleotides can escape exonuclease causing a replication error,
      the correct nucleotide may get sacrificed unnecessarily by erroneous cleavage.
      The interplay of polymerase and exonuclease activities of a DNAP is explored here
      by developing a minimal stochastic kinetic model of DNA replication. Exact
      analytical expressions are derived for a few key statistical distributions; these
      characterize the temporal patterns in the mechanical stepping and the chemical
      (cleavage) reaction. The Michaelis-Menten-like analytical expression derived for
      the average rates of these two processes not only demonstrate the effects of
      their coupling, but are also utilized to measure the extent of replication error
      and erroneous cleavage.

PMID- 23005459
TI  - Torque transfer coefficient in DNA under torsional stress.
AB  - In recent years, significant progress in understanding the properties of
      supercoiled DNA has been obtained due to nanotechniques that made stretching and
      twisting of single molecules possible. Quantitative interpretation of such
      experiments requires accurate knowledge of torques inside manipulated DNA. This
      paper argues that it is not possible to transfer the entire magnitudes of
      external torques to the twisting stress of the double helix, and that a reducing
      torque transfer coefficient (TTC < 1) should always be assumed. This assertion
      agrees with simple physical intuition and is supported by the results of all-atom
      molecular dynamics (MD) simulations. According to MD, the TTCs around 0.8 are
      observed in nearly optimal conditions. Reaching higher values requires special
      efforts and it should be difficult in practice. The TTC can be partially
      responsible for the persistent discrepancies between the twisting rigidity of DNA
      measured by different methods.

PMID- 23005460
TI  - Efficient estimation of energy transfer efficiency in light-harvesting complexes.
AB  - The fundamental physical mechanisms of energy transfer in photosynthetic
      complexes is not yet fully understood. In particular, the degree of efficiency or
      sensitivity of these systems for energy transfer is not known given their
      realistic with surrounding photonic and phononic environments. One major problem
      in studying light-harvesting complexes has been the lack of an efficient method
      for simulation of their dynamics in biological environments. To this end, here we
      revisit the second order time-convolution (TC2) master equation and examine its
      reliability beyond extreme Markovian and perturbative limits. In particular, we
      present a derivation of TC2 without making the usual weak system-bath coupling
      assumption. Using this equation, we explore the long-time behavior of exciton
      dynamics of Fenna-Matthews-Olson (FMO) portein complex. Moreover, we introduce a
      constructive error analysis to estimate the accuracy of TC2 equation in
      calculating energy transfer efficiency, exhibiting reliable performance for
      system-bath interactions with weak and intermediate memory and strength.
      Furthermore, we numerically show that energy transfer efficiency is optimal and
      robust for the FMO protein complex of green sulfur bacteria with respect to
      variations in reorganization energy and bath correlation time scales.

PMID- 23005461
TI  - Swarming behavior of gradient-responsive Brownian particles in a porous medium.
AB  - Active targeting by Brownian particles in a fluid-filled porous environment is
      investigated by computer simulation. The random motion of the particles is
      enhanced by diffusiophoresis with respect to concentration gradients of chemical
      signals released by the particles in the proximity of a target. The mathematical
      model, based on a combination of the Brownian dynamics method and a diffusion
      problem is formulated in terms of key parameters that include the particle
      diffusiophoretic mobility and the signaling threshold (the distance from the
      target at which the particles release their chemical signals). The results
      demonstrate that even a relatively simple chemical signaling scheme can lead to a
      complex collective behavior of the particles and can be a very efficient way of
      guiding a swarm of Brownian particles towards a target, similarly to the way
      colonies of living cells communicate via secondary messengers.

PMID- 23005462
TI  - Anisotropic spherical head model and its application to imaging electric activity
      of the brain.
AB  - This study reports on a solution to Poisson's equation describing an electric
      potential and field generated by a dipolar current source positioned inside a set
      of concentric spherical shells characterized by a homogeneous anisotropic
      conductivity inside each shell. Formulas giving a unique continuation of
      potentials and fields between the shells are derived. The formulas are applied to
      a spherical model of the human head to show that (i) real human skulls comprising
      isotropic compact and cancellous bone layers can be closely approximated by a
      single shell with radial-tangential conductivity anisotropy ~1:2 and radial
      conductivity equal to 1/30 of the brain/scalp conductivity; (ii) errors due to
      the spherical approximation of the head shape are of the same magnitude as errors
      due to poorly known electrical properties of the modeled head tissues; (iii)
      commonly used electroencephalography (EEG) average reference contributes 15% of
      the signal (on the average) and, therefore, makes EEG measurements significantly
      nonlocal; and (iv) the surface Laplacian of EEG measurements closely approximates
      electric currents at the skull-scalp interface, providing a parameter-free (up to
      a constant factor) deblurring and dereferencing of EEG data. These results can be
      useful for localization of sources underlying electric activity of the brain.

PMID- 23005463
TI  - Measuring chromosome conformation with degenerate labels.
AB  - Although DNA conformation plays an integral role in all genetic processes from
      transcription to chromosome segregation, there is as yet no tractable method for
      capturing the in vivo conformation of a chromosome at high resolution. Labeling
      and fluorescently imaging thousands of loci along the chromosome would readily
      yield a conformation if each locus could be uniquely distinguished in the image,
      but this would unrealistically require thousands of distinguishable labels and a
      tedious experimental process. Here we present a computational method for
      extracting conformations when the total number of labels far exceeds the number
      of distinguishable labels. We evaluate our technique using simulated
      conformations with lengths ranging from 10 to 100 kilobases, and discuss the
      prospects for an experiment.

PMID- 23005464
TI  - Stochastic fluctuations of the transmission rate in the susceptible-infected
      susceptible epidemic model.
AB  - We analyze the dynamics of the susceptible-infected-susceptible epidemic model
      when the transmission rate displays Gaussian white noise fluctuations around its
      mean value. We obtain analytic expressions for the final size distribution of
      infectives and the mean infected number of individuals. The model displays a
      variety of noise-induced transitions as a function of the basic reproductive rate
      and the noise intensity. We derive a threshold criterion for epidemic invasion in
      the presence of external noise and determine the mean epidemic duration and the
      mean epidemic extinction time.

PMID- 23005465
TI  - Phenotypic plasticity stimulated by cooperation fosters pattern diversity of
      bacterial colonies.
AB  - Colonies of flagellated bacteria on agar plates are known to take on diverse
      morphologies. A diffusion-reaction model is proposed for bacterial-colony pattern
      formation on a surface due to time scale separation between the slow mass
      migration of bacteria from the point of inoculation, and the fast, but localized,
      dynamics of bacterial phenotypic plasticity stimulated by public-goods
      cooperation and phenotypic switching. By considering two switchable phenotypes in
      the population, the model generates pattern diversity typifying those reported by
      experimental studies.

PMID- 23005466
TI  - Effective driving force applied on DNA inside a solid-state nanopore.
AB  - A detailed understanding of the origin of the electrophoretic force on DNA
      molecules in a solid-state nanopore is important for the development of nanopore
      based sequencing technologies. Because of the discrepancies between recent
      attempts to predict this force and both direct and indirect experimental
      measurements, this topic has been the focus of much recent discussion. We show
      that the force is predictable to very good accuracy if all of the experimental
      conditions are accounted for properly. To resolve this issue, we compare the
      calculation efficiency and accuracy of numerical solutions of Poisson-Boltzmann
      and Poisson-Nernst-Planck descriptions of electrolyte behavior in the nanopore in
      the presence of DNA molecules. Two geometries--axially symmetric and cross
      sectional--are compared and shown to be compatible. Numerical solutions are
      carried out on a sufficiently fine mesh to evaluate the viscous drag force acting
      on DNA inside a silicon nitride nanopore. By assuming the DNA is immobilized in
      the axial center of the nanopore, the calculation result of this viscous drag
      force is found to be rather larger than the experimental result. Because the
      viscous drag force decreases if DNA is closer to the surface of the nanopore,
      however, the relevant effective driving force is the average over all possible
      positions of the DNA in the nanopore. When this positional uncertainty is taken
      into account, the effective driving force acting on DNA inside the nanopore is
      found to agree very well with the experimental results.

PMID- 23005467
TI  - Growth of stochastic resonance in neuronal ensembles with the input signal
      intensity.
AB  - The presence of noise can improve the response of certain nonlinear systems to
      input signals through the effects of stochastic resonance (SR). The optimal noise
      intensity for SR is proportional to the signal frequency if the signal is
      periodic, but proportional to the signal intensity if the signal is aperiodic.
      Here, we demonstrate using linear response theory that the optimal noise
      intensity for SR is necessarily dependent on the signal intensity even if the
      signal is periodic. We also demonstrate that the SR curves grow according to the
      signal intensity from a bell-shaped curve to a plateau, resulting in the
      emergence of SR without tuning. In particular, we present a theoretical analysis
      indicating that the SR peak shifts with the signal intensity due to the scaling
      of the stationary neuronal firings. The growth of SR may serve as a useful design
      principle for many noise-exploiting applications.

PMID- 23005468
TI  - Model selection for athermal cross-linked fiber networks.
AB  - Athermal random fiber networks are usually modeled by representing each fiber as
      a truss, a Euler-Bernoulli or a Timoshenko beam, and, in the case of cross-linked
      networks, each cross-link as a pinned, rotating, or welded joint. In this work we
      study the effect of these various modeling options on the dependence of the
      overall network stiffness on system parameters. We conclude that Timoshenko beams
      can be used for the entire range of density and beam stiffness parameters, while
      the Euler-Bernoulli model can be used only at relatively low network densities.
      In the high density-high bending stiffness range, strain energy is stored
      predominantly in the axial and shear deformation modes, while in the other
      extreme range of parameters, the energy is stored in the bending mode. The effect
      of the model size on the network stiffness is also discussed.

PMID- 23005469
TI  - Multifractal dynamics of turbulent flows in swimming bacterial suspensions.
AB  - We experimentally investigate the self-propelled two-dimensional turbulent flows
      of Escherichia coli suspensions in thin liquid films at two different cell
      concentrations. It is found that the flow has fluctuating vortices with a broad
      range of scales and intensities through the nonlinear interaction of the swimming
      bacteria. Increasing cell concentration increases the total propelling power and
      the nonlinear interaction. It causes the generation of vortices with larger
      scale, lower frequency, and higher intensity. It also widens the histograms of
      the flow velocity and the velocity increment between two spatially separated
      points with more stretched non-Gaussian tails. From the scaling analysis of the
      structure function S(q)(r) of the qth moment of the velocity increment between
      two points with spatial separation r, nonlinear relations between the scaling
      exponent zeta(q) of S(q)(r) and q are found for both cell concentrations, which
      manifests the multifractal dynamics. The multifractality can be enhanced by
      increasing cell concentration.

PMID- 23005470
TI  - Effect of synaptic plasticity on the structure and dynamics of disordered
      networks of coupled neurons.
AB  - In an all-to-all network of integrate-and-fire neurons in which there is a
      disorder in the intrinsic oscillatory frequencies of the neurons, we show that
      through spike-timing-dependent plasticity the synapses which have the high
      frequency neurons as presynaptic tend to be potentiated while the links
      originated from the low-frequency neurons are weakened. The emergent effective
      flow of directed connections introduces the high-frequency neurons as the more
      influential elements in the network and facilitates synchronization by decreasing
      the synaptic cost for onset of synchronization.

PMID- 23005471
TI  - Intrinsic mean-square displacements in proteins.
AB  - The thermal mean-square displacement (MSD) of hydrogen in proteins and its
      associated hydration water is measured by neutron scattering experiments and used
      an indicator of protein function. The observed MSD as currently determined
      depends on the energy resolution width of the neutron scattering instrument
      employed. We propose a method for obtaining the intrinsic MSD of H in the
      proteins, one that is independent of the instrument resolution width. The
      intrinsic MSD is defined as the infinite time value of (r(2)) that appears in the
      Debye-Waller factor. The method consists of fitting a model to the resolution
      broadened elastic incoherent structure factor or to the resolution dependent MSD.
      The model contains the intrinsic MSD, the instrument resolution width, and a rate
      constant characterizing the motions of H in the protein. The method is
      illustrated by obtaining the intrinsic MSD (r(2)) of heparan sulphate (HS-0.4),
      ribonuclease A, and staphysloccal nuclase (SNase) from data in the literature.

PMID- 23005472
TI  - Tactic direction determined by the interaction between oscillatory chemical waves
      and rheological deformation in an amoeba.
AB  - The survival of an organism can depend upon the direction in which it decides to
      move in response to changes in external conditions. Here we propose a
      physicochemical mechanism of the decision process for migration direction in the
      case of a giant amoebalike Physarum plasmodium. The tactical movement response
      could be changed by reversal of the phase wave of the rhythmic contractions that
      occur in any part of the plasmodium body when local stimulation is applied and
      the frequency of the rhythmic contractions is locally modulated in the stimulated
      region. The proposed model describes a physicochemical mechanism of coupling
      between the local modulation of frequency and the global transport of
      protoplasmic mass. The decision process is clarified from a rheological point of
      view.

PMID- 23005473
TI  - Emergence of diversity in a model ecosystem.
AB  - The biological requirements for an ecosystem to develop and maintain species
      diversity are in general unknown. Here we consider a model ecosystem of sessile
      and mutually excluding organisms competing for space [Mathiesen et al. Phys. Rev.
      Lett. 107, 188101 (2011)]. Competition is controlled by an interaction network
      with fixed links chosen by a Bernoulli process. New species are introduced in the
      system at a predefined rate. In the limit of small introduction rates, the system
      becomes bistable and can undergo a phase transition from a state of low diversity
      to high diversity. We suggest that isolated patches of metapopulations formed by
      the collapse of cyclic relations are essential for the transition to the state of
      high diversity.

PMID- 23005474
TI  - Randomly evolving idiotypic networks: structural properties and architecture.
AB  - We consider a minimalistic dynamic model of the idiotypic network of B
      lymphocytes. A network node represents a population of B lymphocytes of the same
      specificity (idiotype), which is encoded by a bit string. The links of the
      network connect nodes with complementary and nearly complementary bit strings,
      allowing for a few mismatches. A node is occupied if a lymphocyte clone of the
      corresponding idiotype exists; otherwise it is empty. There is a continuous
      influx of new B lymphocytes of random idiotype from the bone marrow. B
      lymphocytes are stimulated by cross-linking their receptors with complementary
      structures. If there are too many complementary structures, steric hindrance
      prevents cross-linking. Stimulated cells proliferate and secrete antibodies of
      the same idiotype as their receptors; unstimulated lymphocytes die. Depending on
      few parameters, the autonomous system evolves randomly towards patterns of highly
      organized architecture, where the nodes can be classified into groups according
      to their statistical properties. We observe and describe analytically the
      building principles of these patterns, which make it possible to calculate number
      and size of the node groups and the number of links between them. The
      architecture of all patterns observed so far in simulations can be explained this
      way. A tool for real-time pattern identification is proposed.

PMID- 23005475
TI  - Randomly evolving idiotypic networks: modular mean field theory.
AB  - We develop a modular mean field theory for a minimalistic model of the idiotypic
      network. The model comprises the random influx of new idiotypes and a
      deterministic selection. It describes the evolution of the idiotypic network
      towards complex modular architectures, the building principles of which are
      known. The nodes of the network can be classified into groups of nodes, the
      modules, which share statistical properties. Each node experiences only the mean
      influence of the groups to which it is linked. Given the size of the groups and
      linking between them the statistical properties such as mean occupation, mean
      lifetime, and mean number of occupied neighbors are calculated for a variety of
      patterns and compared with simulations. For a pattern which consists of pairs of
      occupied nodes correlations are taken into account.

PMID- 23005476
TI  - Shape dynamics, lipid hydrodynamics, and the complex viscoelasticity of bilayer
      membranes [corrected].
AB  - Biological membranes are continuously brought out of equilibrium, as they shape
      organelles, package and transport cargo, or respond to external actions. Even the
      dynamics of plain lipid membranes in experimental model systems are very complex
      due to the tight interplay between the bilayer architecture, the shape dynamics,
      and the rearrangement of the lipid molecules. We formulate and numerically
      implement a continuum model of the shape dynamics and lipid hydrodynamics, which
      describes the bilayer by its midsurface and by a lipid density field for each
      monolayer. The viscoelastic response of bilayers is determined by the stretching
      and curvature elasticity, and by the inter-monolayer friction and the membrane
      interfacial shear viscosity. While the bilayer equilibria are well understood
      theoretically, dynamical calculations have relied on simplified continuum
      approaches of uncertain transferability, or on molecular simulations reaching
      very limited length and time scales. Our approach incorporates the main physics,
      is fully nonlinear, does not assume predefined shapes, and can access a wide
      range of time and length scales. We validate it with the well understood tether
      extension. We investigate the tubular lipid transport between cells, the dynamics
      of bud absorption by a planar membrane, and the fate of a localized lipid density
      asymmetry in vesicles. These axisymmetric examples bear biological relevance and
      highlight the diversity of dynamical regimes that bilayers can experience.

PMID- 23005477
TI  - Thermal phase transitions for Dicke-type models in the ultrastrong-coupling
      limit.
AB  - We consider the Dicke model in the ultrastrong-coupling limit to investigate
      thermal phase transitions and their precursors at finite particle numbers N for
      bosonic and fermionic systems. We derive partition functions with degeneracy
      factors that account for the number of configurations and derive explicit
      expressions for the Landau free energy. This allows us to discuss the difference
      between the original Dicke (fermionic) and the bosonic case. We find a crossover
      between these two cases that shows up, for example, in the specific heat.

PMID- 23005478
TI  - Traveling glycolytic waves induced by a temperature gradient and determination of
      diffusivities for dense media.
AB  - Here we consider the spatially extended model incorporating the temperature
      dependent autocatalytic coefficient into the Merkin-Needham-Scott version of the
      Selkov system and show that this model with temperature gradient quite reasonably
      explains the experimentally detected traveling glycolytic nonstationary waves,
      which can be attributed as kinematic ones. Additionally, we analyze the influence
      of possibly incorporating diffusion terms into the equations. It is shown that
      the value of diffusivity influences the timetable for the birth of new wave and
      their further evolution. This result could be used as a method for the
      determination of diffusivity.

PMID- 23005479
TI  - Comment on "Frequency-dependent dispersion in porous media".
AB  - In a recent paper, Valdes-Parada and Alvarez-Ramirez [Phys. Rev. E 84, 031201
      (2011)] used the technique of volume averaging to derive a "frequency-dependent"
      dispersion tensor, D(gamma)(*), the goal of which is to describe solute transport
      in porous media undergoing periodic processes. We describe two issues related to
      this dispersion tensor. First, we demonstrate that the definition of D(gamma)(*)
      is erroneous and derive a corrected version, D(gamma)(*c). With this
      modification, the approach of Valdes-Parada and Alvarez-Ramirez becomes strictly
      equivalent to the one devised by Moyne [Adv. Water Res. 20, 63 (1997)]. Second,
      we show that the term "frequency-dependent dispersion" is misleading because
      D(gamma)(*) and D(gamma)(*c) do not depend on the process operating frequency,
      chi. The study carried out by Valdes-Parada and Alvarez-Ramirez represents a
      spectral analysis of the relaxation of D(gamma)(*) towards its steady-state,
      independent of any periodic operation or excitation.

PMID- 23005481
TI  - Assortative and modular networks are shaped by adaptive synchronization
      processes.
AB  - Modular organization and degree-degree correlations are ubiquitous in the
      connectivity structure of biological, technological, and social interacting
      systems. So far most studies have concentrated on unveiling both features in real
      world networks, but a model that succeeds in generating them simultaneously is
      needed. We consider a network of interacting phase oscillators, and an adaptation
      mechanism for the coupling that promotes the connection strengths between those
      elements that are dynamically correlated. We show that, under these
      circumstances, the dynamical organization of the oscillators shapes the topology
      of the graph in such a way that modularity and assortativity features emerge
      spontaneously and simultaneously. In turn, we prove that such an emergent
      structure is associated with an asymptotic arrangement of the collective
      dynamical state of the network into cluster synchronization.

PMID- 23005482
TI  - Self-similar breakup of near-inviscid liquids.
AB  - The final stages of pinchoff and breakup of dripping droplets of near-inviscid
      Newtonian fluids are studied experimentally for pure water and ethanol. High
      speed imaging and image analysis are used to determine the angle and the minimum
      neck size of the cone-shaped extrema of the ligaments attached to dripping
      droplets in the final microseconds before pinchoff. The angle is shown to
      steadily approach the value of 18.0 +/- 0.4 degrees , independently of the
      initial flow conditions or the type of breakup. The filament thins and necks
      following a tau(2/3) law in terms of the time remaining until pinchoff,
      regardless of the initial conditions. The observed behavior confirms theoretical
      predictions.

PMID- 23005483
TI  - Origin of Lorentzian pulses in deterministic chaos.
AB  - Pulses having a temporal Lorentzian shape arise naturally from topological
      changes in flow trajectories or phase-space orbits associated with deterministic
      chaos. The pulses can appear as random intermittent events in the time series of
      observable quantities, and they are the cause of exponential frequency power
      spectra previously observed in magnetically confined plasmas and various
      nonlinear systems.

PMID- 23005484
TI  - Nonlocal effect of plasma resonances on the electron energy-distribution function
      in microwave plasma columns.
AB  - Spatially resolved trace rare gases optical emission spectroscopy was used to
      analyze the electron energy-distribution function (EEDF) in low-pressure argon
      plasma columns sustained by surface waves. At frequencies >1 GHz, in the
      microwave-sustained region, the EEDF departs from a Maxwellian, characterized by
      a depletion of low-energy electrons and a high-energy tail, whereas in the field
      free zone, the EEDF is Maxwellian. Abnormal behavior of the EEDF results from the
      acceleration of low-energy electrons due to the conversion of surface waves into
      volume plasmons at the resonance point where the plasma frequency equals the wave
      frequency and their absorption by either collisional or Landau damping.

PMID- 23005485
TI  - Enhanced response of regular networks to local signals in the presence of a fast
      impurity.
AB  - We consider an array of inductively coupled Josephson junctions with a fast
      impurity (a junction with a smaller value of the critical current) and study the
      consequences of imposing a small amplitude periodic signal at some point in the
      array. We find that when the external signal is imposed at the impurity, the
      response of the array is boosted and a small amplitude signal can be detected
      throughout the array. When the signal is imposed elsewhere, minor effects are
      seen on the dynamics of the array. The same results have also been seen in the
      presence of a single fast-spiking neuron in a chain of diffusively coupled
      FitzHugh-Nagumo neurons.

PMID- 23005486
TI  - Explosive synchronization enhanced by time-delayed coupling.
AB  - This paper deals with the emergence of explosive synchronization in scale-free
      networks by considering the Kuramoto model of coupled phase oscillators. The
      natural frequencies of oscillators are assumed to be correlated with their
      degrees, and a time delay is included in the system. This assumption allows
      enhancing the explosive transition to reach a synchronous state. We provide an
      analytical treatment developed in a star graph, which reproduces results obtained
      in scale-free networks. Our findings have important implications in understanding
      the synchronization of complex networks since the time delay is present in most
      real-world complex systems due to the finite speed of the signal transmission
      over a distance.

PMID- 23005487
TI  - Thermodynamic analysis of low-temperature carbon dioxide and sulfur dioxide
      capture from coal-burning power plants.
AB  - We discuss the possibility of capturing carbon dioxide from the flue gas of a
      coal-fired electrical power plant by cryogenically desublimating the carbon
      dioxide and then preparing it for transport in a pipeline to a sequestration
      site. Various other means have been proposed to accomplish the same goal. The
      problem discussed here is to estimate the "energy penalty" or "parasitic energy
      loss,' defined as the fraction of electrical output that will be needed to
      provide the refrigeration and that will then not be deliverable. We compute the
      energy loss (7.9-9.2% at 1 atm) based on perfect Carnot efficiency and estimate
      the achievable parasitic energy loss (22-26% at 1 atm) by incorporating the
      published coefficient of performance values for appropriately sized refrigeration
      or liquefaction cycles at the relevant temperatures. The analyses at 1 atm
      represent a starting point for future analyses using elevated pressures.

PMID- 23005488
TI  - Relationship between clustering coefficient and the success of cooperation in
      networks.
AB  - In recent years the prisoner's dilemma has become a paradigm for the study of the
      emergence of cooperation in spatially structured populations. Such a structure is
      usually assumed to be given by a graph. In general, the success of cooperative
      strategies is associated with the possibility of forming globular clusters, which
      in turn depends on a feature of the network that is measured by its clustering
      coefficient. In this work we study the dependence of the success of cooperation
      on this coefficient for regular networks. Additionally, for both stochastic and
      deterministic dynamics we show that there is a strong dependence on the initial
      composition of the population. This hints at the existence of several different
      mechanisms that could promote or hinder cluster expansion. We have studied in
      detail some of these mechanisms by concentrating on completely ordered networks
      (large clustering coefficient) or completely random networks (vanishing
      clustering coefficient).

PMID- 23005489
TI  - Bayesian inference for a wave-front model of the neolithization of Europe.
AB  - We consider a wave-front model for the spread of neolithic culture across Europe,
      and use Bayesian inference techniques to provide estimates for the parameters
      within this model, as constrained by radiocarbon data from southern and western
      Europe. Our wave-front model allows for both an isotropic background spread
      (incorporating the effects of local geography) and a localized anisotropic spread
      associated with major waterways. We introduce an innovative numerical scheme to
      track the wave front, and use Gaussian process emulators to further increase the
      efficiency of our model, thereby making Markov chain Monte Carlo methods
      practical. We allow for uncertainty in the fit of our model, and discuss the
      inferred distribution of the parameter specifying this uncertainty, along with
      the distributions of the parameters of our wave-front model. We subsequently use
      predictive distributions, taking account of parameter uncertainty, to identify
      radiocarbon sites which do not agree well with our model. These sites may warrant
      further archaeological study or motivate refinements to the model.

PMID- 23005490
TI  - Oscillatory instability in slow crack propagation in rubber under large
      deformation.
AB  - We performed experiments to investigate slow fracture in thin rubber films under
      uniaxial tension using high-viscosity oils. In this system we observed an
      oscillating instability in slowly propagating cracks for small applied strains.
      The transition between oscillatory and straight patterns occurred near the
      characteristic strain at which rubber exhibits a nonlinear stress-strain
      relation. This suggests that nonlinear elasticity plays an important role in the
      formation of the observed pattern. This was confirmed by numerical simulation for
      neo-Hookean and linear elasticity models.

PMID- 23005491
TI  - Algorithm for parametric community detection in networks.
AB  - Modularity maximization is extensively used to detect communities in complex
      networks. It has been shown, however, that this method suffers from a resolution
      limit: Small communities may be undetectable in the presence of larger ones even
      if they are very dense. To alleviate this defect, various modifications of the
      modularity function have been proposed as well as multiresolution methods. In
      this paper we systematically study a simple model (proposed by Pons and Latapy
      [Theor. Comput. Sci. 412, 892 (2011)] and similar to the parametric model of
      Reichardt and Bornholdt [Phys. Rev. E 74, 016110 (2006)]) with a single parameter
      alpha that balances the fraction of within community edges and the expected
      fraction of edges according to the configuration model. An exact algorithm is
      proposed to find optimal solutions for all values of alpha as well as the
      corresponding successive intervals of alpha values for which they are optimal.
      This algorithm relies upon a routine for exact modularity maximization and is
      limited to moderate size instances. An agglomerative hierarchical heuristic is
      therefore proposed to address parametric modularity detection in large networks.
      At each iteration the smallest value of alpha for which it is worthwhile to merge
      two communities of the current partition is found. Then merging is performed and
      the data are updated accordingly. An implementation is proposed with the same
      time and space complexity as the well-known Clauset-Newman-Moore (CNM) heuristic
      [Phys. Rev. E 70, 066111 (2004)]. Experimental results on artificial and real
      world problems show that (i) communities are detected by both exact and heuristic
      methods for all values of the parameter alpha; (ii) the dendrogram summarizing
      the results of the heuristic method provides a useful tool for substantive
      analysis, as illustrated particularly on a Les Miserables data set; (iii) the
      difference between the parametric modularity values given by the exact method and
      those given by the heuristic is moderate; (iv) the heuristic version of the
      proposed parametric method, viewed as a modularity maximization tool, gives
      better results than the CNM heuristic for large instances.

PMID- 23005492
TI  - Drift instability in the motion of a fluid droplet with a chemically reactive
      surface driven by Marangoni flow.
AB  - We theoretically derive the amplitude equations for a self-propelled droplet
      driven by Marangoni flow. As advective flow driven by surface tension gradient is
      enhanced, the stationary state becomes unstable and the droplet starts to move.
      The velocity of the droplet is determined from a cubic nonlinear term in the
      amplitude equations. The obtained critical point and the characteristic velocity
      are well supported by numerical simulations.

PMID- 23005493
TI  - Potts model based on a Markov process computation solves the community structure
      problem effectively.
AB  - The Potts model is a powerful tool to uncover community structure in complex
      networks. Here, we propose a framework to reveal the optimal number of
      communities and stability of network structure by quantitatively analyzing the
      dynamics of the Potts model. Specifically we model the community structure
      detection Potts procedure by a Markov process, which has a clear mathematical
      explanation. Then we show that the local uniform behavior of spin values across
      multiple timescales in the representation of the Markov variables could naturally
      reveal the network's hierarchical community structure. In addition, critical
      topological information regarding multivariate spin configuration could also be
      inferred from the spectral signatures of the Markov process. Finally an algorithm
      is developed to determine fuzzy communities based on the optimal number of
      communities and the stability across multiple timescales. The effectiveness and
      efficiency of our algorithm are theoretically analyzed as well as experimentally
      validated.

PMID- 23005494
TI  - Solid-on-solid single-block dynamics under mechanical vibration.
AB  - The suppression of friction between sliding objects, modulated or enhanced by
      mechanical vibrations, is well established. However, the precise conditions of
      occurrence of these phenomena are not well understood. Here we address these
      questions focusing on a simple spring-block model, which is relevant to
      investigate friction both at the atomistic as well as the macroscopic scale. This
      allows us to investigate the influence on friction of the properties of the
      external drive, of the geometry of the surfaces over which the block moves, and
      of the confining force. Via numerical simulations and a theoretical study of the
      equations of motion, we identify the conditions under which friction is
      suppressed and/or recovered, and we evidence the critical role played by surface
      modulations and by the properties of the confining force.

PMID- 23005495
TI  - Detecting alternative graph clusterings.
AB  - The problem of graph clustering or community detection has enjoyed a lot of
      attention in complex networks literature. A quality function, modularity,
      quantifies the strength of clustering and on maximization yields sensible
      partitions. However, in most real world networks, there are an exponentially
      large number of near-optimal partitions with some being very different from each
      other. Therefore, picking an optimal clustering among the alternatives does not
      provide complete information about network topology. To tackle this problem, we
      propose a graph perturbation scheme which can be used to identify an ensemble of
      near-optimal and diverse clusterings. We establish analytical properties of
      modularity function under the perturbation which ensures diversity. Our approach
      is algorithm independent and therefore can leverage any of the existing
      modularity maximizing algorithms. We numerically show that our methodology can
      systematically identify very different partitions on several existing data sets.
      The knowledge of diverse partitions sheds more light into the topological
      organization and helps gain a more complete understanding of the underlying
      complex network.

PMID- 23005496
TI  - Detecting the solution space of vertex cover by mutual determinations and
      backbones.
AB  - To solve the combinatorial optimization problems, especially the minimal Vertex
      cover problem with high efficiency, is a significant task in theoretical computer
      science and many other subjects. Aiming at detecting the solution space of Vertex
      cover, a new structure named mutual-determination is defined and discovered for
      Vertex-cover on general graphs, which results in the emergence of strong
      correlations among the unfrozen nodes. Based on the backbones and mutual
      determinations with node ranks by leaf removal, we propose a Mutual-determination
      and Backbone Evolution Algorithm to achieve the reduced solution graph, which
      provides a graphical expression of the solution space of Vertex-cover. By this
      algorithm, the whole solution space and detailed structures such as backbones can
      be obtained strictly when there is no leaf-removal core on the given graph.
      Compared with the current algorithms, the Mutual-determination and Backbone
      Evolution Algorithm performs as well as the replica symmetry one in a certain
      interval but has a small gap higher than the replica symmetric breaking one and
      has a relatively small error for the exact results. The algorithm with the mutual
      determination provides a new viewpoint to solve Vertex-cover and understand the
      organizations of the solution spaces, and the reduced solution graph gives an
      alternative way to catch detailed information of the ground/steady states.

PMID- 23005497
TI  - Scaling laws for impact fragmentation of spherical solids.
AB  - We investigate the impact fragmentation of spherical solid bodies made of
      heterogeneous brittle materials by means of a discrete element model. Computer
      simulations are carried out for four different system sizes varying the impact
      velocity in a broad range. We perform a finite size scaling analysis to determine
      the critical exponents of the damage-fragmentation phase transition and deduce
      scaling relations in terms of radius R and impact velocity v(0). The scaling
      analysis demonstrates that the exponent of the power law distributed fragment
      mass does not depend on the impact velocity; the apparent change of the exponent
      predicted by recent simulations can be attributed to the shifting cutoff and to
      the existence of unbreakable discrete units. Our calculations reveal that the
      characteristic time scale of the breakup process has a power law dependence on
      the impact speed and on the distance from the critical speed in the damaged and
      fragmented states, respectively. The total amount of damage is found to have a
      similar behavior, which is substantially different from the logarithmic
      dependence on the impact velocity observed in two dimensions.

PMID- 23005498
TI  - Electric-field-induced crack patterns: experiments and simulation.
AB  - We report a study of crack patterns formed in laponite gel drying in an electric
      field. The sample dries in a circular petri dish and the field is radial, acting
      inward or outward. A system of radial cracks forms in the setup with the center
      terminal positive, while predominantly cross-radial cracks form when the center
      is at a negative potential. The laponite accumulates near the negative terminal
      making the layer thicker at this end. A spring model on a square lattice is used
      to simulate the desiccation crack formation, with an additional radial force
      acting due to the electric field. With the radial force acting outward, radial
      cracks form and for the reversed field cross-radial cracks form. This conforms to
      the observation that laponite platelets become effectively positive due to
      overcharging and are attracted towards the negative terminal.

PMID- 23005499
TI  - Nonconservative kinetic exchange model of opinion dynamics with randomness and
      bounded confidence.
AB  - The concept of a bounded confidence level is incorporated in a nonconservative
      kinetic exchange model of opinion dynamics model where opinions have continuous
      values ?[-1,1]. The characteristics of the unrestricted model, which has one
      parameter lambda representing conviction, undergo drastic changes with the
      introduction of bounded confidence parametrized by delta. Three distinct regions
      are identified in the phase diagram in the delta-lambda plane and the evidences
      of a first order phase transition for delta >= 0.3 are presented. A neutral state
      with all opinions equal to zero occurs for lambda <= lambda(c1) ? 2/3,
      independent of delta, while for lambda(c(1)) <= lambda <= lambda(c(2))(delta), an
      ordered region is seen to exist where opinions of only one sign prevail. At
      lambda(c(2))(delta), a transition to a disordered state is observed, where
      individual opinions of both signs coexist and move closer to the extreme values
      (+/-1) as lambda is increased. For confidence level delta < 0.3, the ordered
      phase exists for a narrow range of lambda only. The line delta = 0 is apparently
      a line of discontinuity, and this limit is discussed in some detail.

PMID- 23005500
TI  - Epidemics in networks with nodal self-infection and the epidemic threshold.
AB  - Since the Susceptible-Infected-Susceptible (SIS) epidemic threshold is not
      precisely defined in spite of its practical importance, the classical SIS
      epidemic process has been generalized to the epsilon-SIS model, where a node
      possesses a self-infection rate epsilon, in addition to a link infection rate
      beta and a curing rate delta. The exact Markov equations are derived, from which
      the steady state can be computed. The major advantage of the epsilon-SIS model is
      that its steady state is different from the absorbing (or overall-healthy state)
      and approximates, for a certain range of small epsilon > 0, the in reality
      observed phase transition, also called the "metastable" state, that is
      characterized by the epidemic threshold. The exact steady-state analysis for the
      complete graph illustrates the effect of small epsilon and the quality of the
      first-order mean-field approximation, the N-intertwined model, proposed earlier.
      Apart from duality principles, often used in the mathematical literature, we
      present an exact recursion relation for the Markov infinitesimal generator.

PMID- 23005501
TI  - Analysis of interface conversion processes of ballistic and diffusive motion in
      driven superlattices.
AB  - We explore the nonequilibrium dynamics of noninteracting classical particles in a
      one-dimensional driven superlattice which is composed of domains exposed to
      different time-dependent forces. It is shown how the combination of directed
      transport and conversion processes from diffusive to ballistic motion causes
      strong correlations between velocity and phase for particles passing through a
      superlattice. A detailed understanding of the underlying mechanism allows us to
      tune the resulting velocity distributions at distinguished points in the
      superlattice by means of local variations of the applied driving force. As an
      intriguing application we present a scheme how initially diffusive particles can
      be transformed into a monoenergetic pulsed particle beam whose parameters such as
      its energy can be varied.

PMID- 23005502
TI  - Cluster and group synchronization in delay-coupled networks.
AB  - We investigate the stability of synchronized states in delay-coupled networks
      where synchronization takes place in groups of different local dynamics or in
      cluster states in networks with identical local dynamics. Using a master
      stability approach, we find that the master stability function shows a discrete
      rotational symmetry depending on the number of groups. The coupling matrices that
      permit solutions on group or cluster synchronization manifolds show a very
      similar symmetry in their eigenvalue spectrum, which helps to simplify the
      evaluation of the master stability function. Our theory allows for the
      characterization of stability of different patterns of synchronized dynamics in
      networks with multiple delay times, multiple coupling functions, but also with
      multiple kinds of local dynamics in the networks' nodes. We illustrate our
      results by calculating stability in the example of delay-coupled semiconductor
      lasers and in a model for neuronal spiking dynamics.

PMID- 23005503
TI  - Pulsed chaos synchronization in networks with adaptive couplings.
AB  - Networks of chaotic units with static couplings can synchronize to a common
      chaotic trajectory. The effect of dynamic adaptive couplings on the cooperative
      behavior of chaotic networks is investigated. The couplings adjust to the
      activities of its two units by two competing mechanisms: An exponential decrease
      of the coupling strength is compensated for by an increase due to desynchronized
      activity. This mechanism prevents the network from reaching a steady state.
      Numerical simulations of a coupled map lattice show chaotic trajectories of
      desynchronized units interrupted by pulses of mutually synchronized clusters.
      These pulses occur on all scales, sometimes extending to the entire network.
      Clusters of synchronized units can be triggered by a small group of synchronized
      units.

PMID- 23005504
TI  - Dynamics of strain bifurcations in a magnetostrictive ribbon.
AB  - We develop a coupled nonlinear oscillator model involving magnetization and
      strain to explain several experimentally observed dynamical features exhibited by
      forced magnetostrictive ribbon. Here we show that the model recovers the observed
      period-doubling route to chaos as function of the dc field for a fixed ac field
      and quasiperiodic route to chaos as a function of the ac field, keeping the dc
      field constant. The model also predicts induced and suppressed chaos under the
      influence of an additional small-amplitude near-resonant ac field. Our analysis
      suggests rich dynamics in coupled order-parameter systems such as
      magnetomartensitic and magnetoelectric materials.

PMID- 23005505
TI  - Chaotic phase synchronization in bursting-neuron models driven by a weak periodic
      force.
AB  - We investigate the entrainment of a neuron model exhibiting a chaotic spiking
      bursting behavior in response to a weak periodic force. This model exhibits two
      types of oscillations with different characteristic time scales, namely, long and
      short time scales. Several types of phase synchronization are observed, such as
      1:1 phase locking between a single spike and one period of the force and 1:l
      phase locking between the period of slow oscillation underlying bursts and l
      periods of the force. Moreover, spiking-bursting oscillations with chaotic firing
      patterns can be synchronized with the periodic force. Such a type of phase
      synchronization is detected from the position of a set of points on a unit
      circle, which is determined by the phase of the periodic force at each spiking
      time. We show that this detection method is effective for a system with multiple
      time scales. Owing to the existence of both the short and the long time scales,
      two characteristic phenomena are found around the transition point to chaotic
      phase synchronization. One phenomenon shows that the average time interval
      between successive phase slips exhibits a power-law scaling against the driving
      force strength and that the scaling exponent has an unsmooth dependence on the
      changes in the driving force strength. The other phenomenon shows that Kuramoto's
      order parameter before the transition exhibits stepwise behavior as a function of
      the driving force strength, contrary to the smooth transition in a model with a
      single time scale.

PMID- 23005506
TI  - Directed transport in a classical lattice with a high-frequency driving.
AB  - We analyze the dynamics of a classical particle in a spatially periodic potential
      under the influence of a periodic in time uniform force. It was shown by S. Flach
      and coworkers [Phys. Rev. Lett. 84, 2358 (2000)] that despite zero average force,
      directed transport is possible in the system. Asymptotic description of this
      phenomenon for the case of slow driving was developed by X. Leoncini and
      coworkers [Phys. Rev. E 79, 026213 (2009)]. Here we consider the case of fast
      driving using the canonical perturbation theory. An asymptotic formula is derived
      for the average drift velocity as a function of the system parameters and the
      driving law. We show that directed transport arises in an effective Hamiltonian
      that does not possess chaotic dynamics, thereby clarifying the relation between
      chaos and transport in the system. Sufficient conditions for transport are
      derived.

PMID- 23005507
TI  - Wave systems with direct processes and localized losses or gains: the nonunitary
      Poisson kernel.
AB  - We study the scattering of waves in systems with losses or gains simulated by
      imaginary potentials. This is done for a complex delta potential that corresponds
      to a spatially localized absorption or amplification. In the Argand plane the
      scattering matrix moves on a circle C centered on the real axis, but not at the
      origin, that is tangent to the unit circle. From the numerical simulations it is
      concluded that the distribution of the scattering matrix, when measured from the
      center of the circle C, agrees with the nonunitary Poisson kernel. This result is
      also obtained analytically by extending the analyticity condition, of unitary
      scattering matrices, to the no-unitary ones. We use this nonunitary Poisson
      kernel to obtain the distribution of nonunitary scattering matrices when measured
      from the origin of the Argand plane. The obtained marginal distributions have
      excellent agreement with the numerical results.

PMID- 23005508
TI  - Electric-field-sustained spiral waves in subexcitable media.
AB  - We present numerical evidence that, in the presence of a suitable electric field,
      an isolated broken plane wave retracting originally in subexcitable media can
      propagate continuously and eventually evolve into a rotating spiral. Simulations
      for the FitzHugh-Nagumo, the Barkley, and the Oregonator models are carried out
      and the same electric-field-sustained spiral phenomena are observed.
      Semianalytical results in the framework of a kinematic theory are quantitatively
      consistent with the numerical results.

PMID- 23005509
TI  - Vibrational resonance induced by transition of phase-locking modes in excitable
      systems.
AB  - We study the occurrence of vibrational resonance as well as the underlying
      mechanism in excitable systems. The single vibration resonance and vibration bi
      resonance are observed when tuning the amplitude and frequency of high-frequency
      force simultaneously. Furthermore, by virtue of the phase diagram of low
      frequency-signal-free FitzHugh-Nagumo model, it is found that each maxima of
      response measure is located exactly at the transition boundary of phase patterns.
      Therefore, it is the transition between different phase-locking modes that
      induces vibrational resonance in the excitable systems. Finally, this mechanism
      is verified in the Hodgkin-Huxley neural model. Our results provide insights into
      the transmission of weak signals in nonlinear systems, which are valuable in
      engineering for potential applications.

PMID- 23005510
TI  - Tunneling phenomena in the open elliptic quantum billiard.
AB  - The study of open quantum billiards has gained popularity in the last decades,
      including different common and uncommon geometries such as the circular and
      stadium billiards. We present an extensive analysis of the elliptic quantum
      billiard with hyperbolic channels. We concentrate on the tunneling through an
      elliptic resonator-like structure. We analyze three different variations of the
      system: the first configuration has horizontal channels, then we study the system
      with vertical leads, and finally we displace both channels by the same angle to
      gain a more general perspective. We observed a very unusual phase distribution in
      the resonator cavity when there is no tunneling through the system.

PMID- 23005512
TI  - Transition to complete synchronization and global intermittent synchronization in
      an array of time-delay systems.
AB  - We report the nature of transitions from the nonsynchronous to a complete
      synchronization (CS) state in arrays of time-delay systems, where the systems are
      coupled with instantaneous diffusive coupling. We demonstrate that the transition
      to CS occurs distinctly for different coupling configurations. In particular, for
      unidirectional coupling, locally (microscopically) synchronization transition
      occurs in a very narrow range of coupling strength but for a global one
      (macroscopically) it occurs sequentially in a broad range of coupling strength
      preceded by an intermittent synchronization. On the other hand, in the case of
      mutual coupling, a very large value of coupling strength is required for local
      synchronization and, consequently, all the local subsystems synchronize
      immediately for the same value of the coupling strength and, hence, globally,
      synchronization also occurs in a narrow range of the coupling strength. In the
      transition regime, we observe a type of synchronization transition where long
      intervals of high-quality synchronization which are interrupted at irregular
      times by intermittent chaotic bursts simultaneously in all the systems and which
      we designate as global intermittent synchronization. We also relate our
      synchronization transition results to the above specific types using unstable
      periodic orbit theory. The above studies are carried out in a well-known
      piecewise linear time-delay system.

PMID- 23005511
TI  - Phase synchronization of bursting neurons in clustered small-world networks.
AB  - We investigate the collective dynamics of bursting neurons on clustered networks.
      The clustered network model is composed of subnetworks, each of them presenting
      the so-called small-world property. This model can also be regarded as a network
      of networks. In each subnetwork a neuron is connected to other ones with regular
      as well as random connections, the latter with a given intracluster probability.
      Moreover, in a given subnetwork each neuron has an intercluster probability to be
      connected to the other subnetworks. The local neuron dynamics has two time scales
      (fast and slow) and is modeled by a two-dimensional map. In such small-world
      network the neuron parameters are chosen to be slightly different such that, if
      the coupling strength is large enough, there may be synchronization of the
      bursting (slow) activity. We give bounds for the critical coupling strength to
      obtain global burst synchronization in terms of the network structure, that is,
      the probabilities of intracluster and intercluster connections. We find that, as
      the heterogeneity in the network is reduced, the network global synchronizability
      is improved. We show that the transitions to global synchrony may be abrupt or
      smooth depending on the intercluster probability.

PMID- 23005513
TI  - Parameter estimation through ignorance.
AB  - Dynamical modeling lies at the heart of our understanding of physical systems.
      Its role in science is deeper than mere operational forecasting, in that it
      allows us to evaluate the adequacy of the mathematical structure of our models.
      Despite the importance of model parameters, there is no general method of
      parameter estimation outside linear systems. A relatively simple method of
      parameter estimation for nonlinear systems is introduced, based on variations in
      the accuracy of probability forecasts. It is illustrated on the logistic map, the
      Henon map, and the 12-dimensional Lorenz96 flow, and its ability to outperform
      linear least squares in these systems is explored at various noise levels and
      sampling rates. As expected, it is more effective when the forecast error
      distributions are non-Gaussian. The method selects parameter values by minimizing
      a proper, local skill score for continuous probability forecasts as a function of
      the parameter values. This approach is easier to implement in practice than
      alternative nonlinear methods based on the geometry of attractors or the ability
      of the model to shadow the observations. Direct measures of inadequacy in the
      model, the "implied ignorance," and the information deficit are introduced.

PMID- 23005514
TI  - Quantum signatures of an oscillatory instability in the Bose-Hubbard trimer.
AB  - We study the Bose-Hubbard model for three sites in a symmetric, triangular
      configuration and search for quantum signatures of the classical regime of
      oscillatory instabilities, known to appear through Hamiltonian Hopf bifurcations
      for the "single-depleted-well" family of stationary states in the discrete
      nonlinear Schrodinger equation. In the regimes of classical stability, single
      quantum eigenstates with properties analogous to those of the classical
      stationary states can be identified already for rather small particle numbers. On
      the other hand, in the instability regime the interaction with other eigenstates
      through avoided crossings leads to strong mixing, and no single eigenstate with
      classical-like properties can be seen. We compare the quantum dynamics resulting
      from initial conditions taken as perturbed quantum eigenstates and SU(3) coherent
      states, respectively, in a quantum-semiclassical transitional regime of 10-100
      particles. While the perturbed quantum eigenstates do not show a classical-like
      behavior in the instability regime, a coherent state behaves analogously to a
      perturbed classical stationary state, and exhibits initially resonant
      oscillations with oscillation frequencies well described by classical internal
      mode oscillations.

PMID- 23005515
TI  - Finding weak directional coupling in multiscale time series.
AB  - We propose a method to identify the direction of interactions between the
      components of a coupled system from observed data. This method tries to identify
      the direction of coupling for various severe conditions including for nonlinear
      dynamics, small sample size, weak coupling strength, noisy and multiscale data,
      and multistructure systems. Thus, it appears to be a promising method for real
      world problems encountered in a variety of disciplines, such as physics,
      economics, and biology.

PMID- 23005516
TI  - Anomalous transport induced by nonhyperbolicity.
AB  - In this paper we study how deterministic features presented by a system can be
      used to perform direct transport in a quasisymmetric potential and weak
      dissipative system. We show that the presence of nonhyperbolic regions around
      acceleration areas of the phase space plays an important role in the acceleration
      of particles giving rise to direct transport in the system. Such an effect can be
      observed for a large interval of the weak asymmetric potential parameter allowing
      the possibility to obtain useful work from unbiased nonequilibrium fluctuation in
      real systems even in a presence of a quasisymmetric potential.

PMID- 23005517
TI  - Controlling chaos in wave-particle interactions.
AB  - We analyze the behavior of a relativistic particle moving under the influence of
      a uniform magnetic field and a stationary electrostatic wave. We work with a set
      of pulsed waves that allows us to obtain an exact map for the system. We also use
      a method of control for near-integrable Hamiltonians that consists of the
      addition of a small and simple control term to the system. This control term
      creates invariant tori in phase space that prevent chaos from spreading to large
      regions, making the controlled dynamics more regular. We show numerically that
      the control term just slightly modifies the system but is able to drastically
      reduce chaos with a low additional cost of energy. Moreover, we discuss how the
      control of chaos and the consequent recovery of regular trajectories in phase
      space are useful to improve regular particle acceleration.

PMID- 23005518
TI  - Hopf bifurcation to square-wave switching in mutually coupled semiconductor
      lasers.
AB  - Using advanced continuation techniques for dynamical systems, we elucidate the
      bifurcations leading to asymptotically stable square-wave pulsing and
      polarization mode switching in semiconductor lasers with mutual time-delayed and
      polarization rotating coupling. We find that the increase of coupling strength
      leads to a cascade of Hopf bifurcations on a mixed-mode steady state up to a
      transcritical bifurcation on a so-called pure-mode steady state where both lasers
      emit with the injected polarization state. From these successive Hopf
      bifurcations emerge time-periodic solutions that have a period close to the laser
      relaxation oscillation for weak coupling but a period close to twice the time
      delay for large coupling strength. The wave form of the time-periodic solutions
      also evolves from harmonic pulsing up to square-wave pulsing as has been observed
      recently in experiments.

PMID- 23005519
TI  - Thermomagnetic convective flows in a vertical layer of ferrocolloid: perturbation
      energy analysis and experimental study.
AB  - Flow patterns arising in a vertical differentially heated layer of nonconducting
      ferromagnetic fluid placed in an external uniform transverse magnetic field are
      studied experimentally and discussed from the point of view of the perturbation
      energy balance. A quantitative criterion for detecting the parametric point where
      the dominant role in generating a flow instability is transferred between the
      thermogravitational and thermomagnetic mechanisms is suggested, based on the
      disturbance energy balance analysis. A comprehensive experimental study of
      various flow patterns is undertaken, and the existence is demonstrated of oblique
      thermomagnetic waves theoretically predicted by Suslov [Phys. Fluids 20, 084101
      (2008)] and superposed onto the stationary magnetoconvective pattern known
      previously. It is found that the wave number of the detected convection patterns
      depends sensitively on the temperature difference across the layer and on the
      applied magnetic field. In unsteady regimes its value varies periodically by a
      factor of almost 2, indicating the appearance of two different competing wave
      modes. The wave numbers and spatial orientation of the observed dominant flow
      patterns are found to be in good agreement with theoretical predictions.

PMID- 23005520
TI  - Analytical modeling for heat transfer in sheared flows of nanofluids.
AB  - We developed a model for the enhancement of the heat flux by spherical and
      elongated nanoparticles in sheared laminar flows of nanofluids. Besides the heat
      flux carried by the nanoparticles, the model accounts for the contribution of
      their rotation to the heat flux inside and outside the particles. The rotation of
      the nanoparticles has a twofold effect: it induces a fluid advection around the
      particle and it strongly influences the statistical distribution of particle
      orientations. These dynamical effects, which were not included in existing
      thermal models, are responsible for changing the thermal properties of flowing
      fluids as compared to quiescent fluids. The proposed model is strongly supported
      by extensive numerical simulations, demonstrating a potential increase of the
      heat flux far beyond the Maxwell-Garnett limit for the spherical nanoparticles.
      The road ahead, which should lead toward robust predictive models of heat flux
      enhancement, is discussed.

PMID- 23005521
TI  - Coarsening dynamics of dewetting nanodroplets on chemically patterned substrates.
AB  - Mesoscopic hydrodynamic equations are solved to investigate coarsening dynamics
      of two interacting nanodroplets on chemically patterned substrates. The effects
      of different parameters such as the surface chemical pattern, the slip length,
      the profile of the disjoining pressure, the size of the droplets, and the contact
      angles on the coarsening are studied. Our results reveal that the presence of a
      chemical heterogeneity can enhance or weaken the coarsening dynamics depending on
      the pattern type and positions of the droplets on the substrate. Also increasing
      the contact angles to values larger than a critical value may qualitatively
      change the coarsening process, and the profile of the disjoining pressure and the
      slippage can appreciably modify the coarsening rate.

PMID- 23005522
TI  - Propulsive performance of a body with a traveling-wave surface.
AB  - A body with a traveling-wave surface (TWS) is investigated by solving the
      incompressible Navier-Stokes equation numerically to understand the mechanisms of
      a novel propulsive strategy. In this study, a virtual model of a foil with a
      flexible surface which performs a traveling-wave movement is used as a free
      swimming body. Based on the simulations by varying the traveling-wave Reynolds
      number and the amplitude and wave number of the TWS, some propulsive properties
      including the forward speed, the swimming efficiency, and the flow field are
      analyzed in detail. It is found that the mean forward velocity increases with the
      traveling-wave Reynolds number, the amplitude, and the wave number of the TWS. A
      weak wake behind the free swimming body is identified and the propulsive
      mechanisms are discussed. Moreover, the TWS is a "quiet" propulsive approach,
      which is an advantage when preying. The results obtained in this study provide a
      novel propulsion concept, which may also lead to an important design capability
      for underwater vehicles.

PMID- 23005523
TI  - Vacuum formation behind the expansion wave in a piston motion problem.
AB  - Long time behavior of one-dimensional gas motion caused by pulling a piston with
      a high speed is numerically studied on the basis of the kinetic theory of gases.
      It is clarified that (i) if the piston speed is lower than a critical speed, the
      state of the gas time-asymptotically approaches the local equilibrium that
      corresponds to the isentropic solution in the conventional gas dynamics, namely,
      an expansion wave followed by a uniform state, and (ii) otherwise, there appears
      a highly nonequilibrium region with a very low pressure behind the expansion
      tail. In the latter case, the components of temperature parallel and
      perpendicular to the flow direction become highly different, and the density
      tends to vanish as time goes on, forming a vacuum region behind the tail at the
      infinite time.

PMID- 23005524
TI  - Anomalous dynamics of capillary rise in porous media.
AB  - The anomalous dynamics of capillary rise in a porous medium discovered
      experimentally more than a decade ago [T. Delker et al., Phys. Rev. Lett. 76,
      2902 (1996)] is described. The developed theory is based on considering the
      principal modes of motion of the menisci that collectively form the wetting front
      on the Darcy scale. These modes, which include (i) dynamic wetting mode, (ii)
      threshold mode, and (iii) interface depinning process, are incorporated into the
      boundary conditions for the bulk equations formulated in the regular framework of
      continuum mechanics of porous media, thus allowing one to consider a general case
      of three-dimensional flows. The developed theory makes it possible to describe
      all regimes observed in the experiment, with the time spanning more than four
      orders of magnitude, and highlights the dominant physical mechanisms at different
      stages of the process.

PMID- 23005525
TI  - Fluid mechanics in fluids at rest.
AB  - Using readily available experimental thermophoretic particle-velocity data it is
      shown, contrary to current teachings, that for the case of compressible flows
      independent dye- and particle-tracer velocity measurements of the local fluid
      velocity at a point in a flowing fluid do not generally result in the same fluid
      velocity measure. Rather, tracer-velocity equality holds only for incompressible
      flows. For compressible fluids, each type of tracer is shown to monitor a
      fundamentally different fluid velocity, with (i) a dye (or any other such
      molecular-tagging scheme) measuring the fluid's mass velocity v appearing in the
      continuity equation and (ii) a small, physicochemically and thermally inert,
      macroscopic (i.e., non-Brownian), solid particle measuring the fluid's volume
      velocity v(v). The term "compressibility" as used here includes not only pressure
      effects on density, but also temperature effects thereon. (For example, owing to
      a liquid's generally nonzero isobaric coefficient of thermal expansion,
      nonisothermal liquid flows are to be regarded as compressible despite the general
      perception of liquids as being incompressible.) Recognition of the fact that two
      independent fluid velocities, mass- and volume-based, are formally required to
      model continuum fluid behavior impacts on the foundations of contemporary
      (monovelocity) fluid mechanics. Included therein are the Navier-Stokes-Fourier
      equations, which are now seen to apply only to incompressible fluids (a fact well
      known, empirically, to experimental gas kineticists). The findings of a
      difference in tracer velocities heralds the introduction into fluid mechanics of
      a general bipartite theory of fluid mechanics, bivelocity hydrodynamics [Brenner,
      Int. J. Eng. Sci. 54, 67 (2012)], differing from conventional hydrodynamics in
      situations entailing compressible flows and reducing to conventional
      hydrodynamics when the flow is incompressible, while being applicable to both
      liquids and gases.

PMID- 23005526
TI  - Optimal energy-utilization ratio for long-distance cruising of a model fish.
AB  - The efficiency of total energy utilization and its optimization for long-distance
      migration of fish have attracted much attention in the past. This paper presents
      theoretical and computational research, clarifying the above well-known classic
      questions. Here, we specify the energy-utilization ratio (f(eta)) as a scale of
      cruising efficiency, which consists of the swimming speed over the sum of the
      standard metabolic rate and the energy consumption rate of muscle activities per
      unit mass. Theoretical formulation of the function f(eta) is made and it is shown
      that based on a basic dimensional analysis, the main dimensionless parameters for
      our simplified model are the Reynolds number (Re) and the dimensionless quantity
      of the standard metabolic rate per unit mass (R(pm)). The swimming speed and the
      hydrodynamic power output in various conditions can be computed by solving the
      coupled Navier-Stokes equations and the fish locomotion dynamic equations. Again,
      the energy consumption rate of muscle activities can be estimated by the quotient
      of dividing the hydrodynamic power by the muscle efficiency studied by previous
      researchers. The present results show the following: (1) When the value of f(eta)
      attains a maximum, the dimensionless parameter R(pm) keeps almost constant for
      the same fish species in different sizes. (2) In the above cases, the tail beat
      period is an exponential function of the fish body length when cruising is
      optimal, e.g., the optimal tail beat period of Sockeye salmon is approximately
      proportional to the body length to the power of 0.78. Again, the larger fish's
      ability of long-distance cruising is more excellent than that of smaller fish.
      (3) The optimal swimming speed we obtained is consistent with previous
      researchers' estimations.

PMID- 23005527
TI  - Vortex merger and topological changes in two-dimensional turbulence.
AB  - On the basis of the critical point analysis, we study the reconnection process of
      vorticity contours associated with coherent vortices in two-dimensional
      turbulence. After checking topological integrity by the Euler index theorem, we
      make use of the critical points and their connectivity (so-called surface
      networks) to characterize topological changes of vorticity contours. We quantify
      vortex merger by computing the number of centers and saddles of the vorticity
      field systematically. Surface networks are topological graphs consisting of the
      critical points and edges connecting them. They can tell in particular which
      vortices are going to merge in near future. Moreover, we show how this method can
      remarkably distinguish the dynamics of the vorticity field in the Navier-Stokes
      equations and that of the Charney-Hasegawa-Mima equation. The relationship
      between the number of the critical points and hyperpalinstrophy is discussed by
      deriving the so-called generalized Rice theorem in the spirit of S. Goto and J.
      C. Vassilicos [Phys. Fluids 21, 035104-1 (2009)]. The Okubo-Weiss' conditional
      sampling is used to compare reconnection in elliptic and hyperbolic regions. A
      comparison has been made between topological changes of the vorticity and that of
      a passive scalar. A study in inviscid flows with different resolutions is also
      given.

PMID- 23005528
TI  - Simulations of the kinematic dynamo onset of spherical Couette flows with smooth
      and rough boundaries.
AB  - We study numerically the dynamo transition of an incompressible electrically
      conducting fluid filling the gap between two concentric spheres. In a first
      series of simulations, the fluid is driven by the rotation of a smooth inner
      sphere through no-slip boundary conditions, whereas the outer sphere is
      stationary. In a second series a volume force intended to simulate a rough
      surface drives the fluid next to the inner sphere within a layer of thickness one
      tenth of the gap width. We investigate the effect of the boundary layer thickness
      on the dynamo threshold in the turbulent regime. The simulations show that the
      boundary forcing simulating the rough surface lowers the necessary rotation rate,
      which may help to improve spherical dynamo experiments.

PMID- 23005529
TI  - Experimental study of spatiotemporally localized surface gravity water waves.
AB  - We present experimental results on the study of spatiotemporally localized
      surface wave events on deep water that can be modeled using the Peregrine
      breather solution of the nonlinear Schrodinger equation. These are often
      considered as prototypes of oceanic rogue waves that can focus wave energy into a
      single wave packet. For small steepness values of the carrier gravity waves the
      Peregrine breathers are relatively wide, thus providing an excellent agreement
      between the theory and experimental results. For larger steepnesses the focusing
      leads to temporally and spatially shorter events. Nevertheless, agreement between
      measurements and the Peregrine breather theory remains reasonably good, with
      discrepancies of modulation gradients and spatiotemporal symmetries being
      tolerable. Lifetimes and travel distances of the spatiotemporally localized wave
      events determined from the experiment are in good agreement with the theory.

PMID- 23005530
TI  - Instabilities in the Rayleigh-Benard-Eckart problem.
AB  - This study is a linear stability analysis of the flows induced by ultrasound
      acoustic waves (Eckart streaming) within an infinite horizontal fluid layer
      heated from below. We first investigate the dependence of the instability
      threshold on the normalized acoustic beam width H(b) for an isothermal fluid
      layer. The critical curve, given by the critical values of the acoustic streaming
      parameter, A(c), has a minimum for a beam width H(b) ~ 0.32. This curve, which
      corresponds to the onset of oscillatory instabilities, compares well with that
      obtained for a two-dimensional cavity of large aspect ratio [A(x) =
      (length/height) = 10]. For a fluid layer heated from below subject to acoustic
      waves (the Rayleigh-Benard-Eckart problem), the influence of the acoustic
      streaming parameter A on the stability threshold is investigated for various
      values of the beam width H(b) and different Prandtl numbers Pr. It is shown that,
      for not too small values of the Prandtl number (Pr > Pr(l)), the acoustic
      streaming delays the appearance of the instabilities in some range of the
      acoustic streaming parameter A. The critical curves display two behaviors. For
      small or moderate values of A, the critical Rayleigh number Ra(c) increases with
      A up to a maximum. Then, when A is further increased, Ra(c) undergoes a decrease
      and eventually goes to 0 at A = A(c), i.e., at the critical value of the
      isothermal case. Large beam widths and large Prandtl numbers give a better
      stabilizing effect. In contrast, for Prandtl numbers below the limiting value
      Pr(l) (which depends on H(b)), stabilization cannot be obtained. The
      instabilities in the Rayleigh-Benard-Eckart problem are oscillatory and
      correspond to right- or left-traveling waves, depending on the parameter values.
      Finally, energy analyses of the instabilities at threshold have indicated that
      the change of the thresholds can be connected to the modifications induced by the
      streaming flow on the critical perturbations.

PMID- 23005531
TI  - Breakdown of chiral symmetry during saturation of the Tayler instability.
AB  - We study spontaneous breakdown of chiral symmetry during the nonlinear evolution
      of the Tayler instability. We start with an initial steady state of zero
      helicity. Within linearized perturbation calculations, helical perturbations of
      this initial state have the same growth rate for either sign of helicity. Direct
      numerical simulations (DNS) of the fully nonlinear equations, however, show that
      an infinitesimal excess of one sign of helicity in the initial perturbation gives
      rise to a saturated helical state. We further show that this symmetry breaking
      can be described by weakly nonlinear finite-amplitude equations with undetermined
      coefficients which can be deduced solely from symmetry consideration. By fitting
      solutions of the amplitude equations to data from DNS, we further determine the
      coefficients of the amplitude equations.

PMID- 23005532
TI  - Role of surface shape on boundary slip and velocity defect.
AB  - Although many gas-phase microfluidic devices contain curved surfaces, relatively
      little research has been conducted on the degree of slip over nonplanar surfaces.
      The present study demonstrates the influence of the surface shape (i.e.,
      convex/concave) on the velocity slip and formation of the Knudsen layer. In
      addition, the study reveals that there is a simple relationship between the shear
      stress exerted on the surface and the velocity defect in the Knudsen layer.

PMID- 23005533
TI  - Nonperturbative renormalization group study of the stochastic Navier-Stokes
      equation.
AB  - We study the renormalization group flow of the average action of the stochastic
      Navier-Stokes equation with power-law forcing. Using Galilean invariance, we
      introduce a nonperturbative approximation adapted to the zero-frequency sector of
      the theory in the parametric range of the Holder exponent 4-2epsilon of the
      forcing where real-space local interactions are relevant. In any spatial
      dimension d, we observe the convergence of the resulting renormalization group
      flow to a unique fixed point which yields a kinetic energy spectrum scaling in
      agreement with canonical dimension analysis. Kolmogorov's -5/3 law is, thus,
      recovered for epsilon = 2 as also predicted by perturbative renormalization. At
      variance with the perturbative prediction, the -5/3 law emerges in the presence
      of a saturation in the epsilon dependence of the scaling dimension of the eddy
      diffusivity at epsilon = 3/2 when, according to perturbative renormalization, the
      velocity field becomes infrared relevant.

PMID- 23005534
TI  - Temperature and intensity of sonoluminescence radiation in sulfuric acid.
AB  - The spectral radiation of sonoluminescence (SL) from sulfuric acid doped with
      various Xe concentrations has been studied in a hydrochemical simulation,
      including radiation effects of both continuum and line emissions. The simulation
      considers the same temperature for both continuum and line parts of the SL
      spectrum and gives results in agreement with the experiment. Also, it can
      properly show period-doubling dynamics for a 50 torr bubble. For most of the
      allowable driving pressures, it is shown that both the temperature and the
      intensity of SL for a 4 torr bubble are greater than those of a 50 torr bubble.
      However, for the range of pressures near the maximum driving conditions of the 50
      torr bubble, the SL intensity of this bubble can be up to three orders of
      magnitude greater than the 4 torr bubble. This case, which is in agreement with
      the experiment, is obtained when the light-emitting region of the 50 torr bubble
      is about three orders of magnitude greater than the 4 torr bubble.

PMID- 23005535
TI  - Horizontal flow and capillarity-driven redistribution in porous media.
AB  - A recent macroscopic mixture theory for two-phase immiscible displacement in
      porous media has introduced percolating and nonpercolating phases. Quasi-analytic
      solutions are computed and compared to the traditional theory. The solutions
      illustrate physical insights and effects due to spatiotemporal changes of
      nonpercolating phases, and they highlight the differences from traditional
      theory. Two initial and boundary value problems are solved in one spatial
      dimension. In the first problem a fluid is displaced by another fluid in a
      horizontal homogeneous porous medium. The displacing fluid is injected with a
      flow rate that keeps the saturation constant at the injection point. In the
      second problem a horizontal homogeneous porous medium is considered which is
      divided into two subdomains with different but constant initial saturations.
      Capillary forces lead to a redistribution of the fluids. Errors in the literature
      are reported and corrected.

PMID- 23005536
TI  - Ion-conserving Poisson-Boltzmann theory.
AB  - It is well known that the Poisson-Nernst-Planck (PNP) theory and the classical
      Gouy-Chapman theory are inconsistent at a high applied voltage. For solving this
      problem, we propose an ion-conserving Poisson-Boltzmann theory, which shows
      remarkable agreement with the numerical PNP solutions, even at a high applied
      voltage. In other words, we have found the exact analytical solutions for steady
      PNP equations; we believe that this finding greatly contributes to understanding
      surface science between solids and liquids.

PMID- 23005537
TI  - Role of rough surface topography on gas slip flow in microchannels.
AB  - We conduct a lattice Boltzmann simulation of gas slip flow in microchannels
      incorporating rough surface effects as characterized by fractal geometry with a
      focus on gas-solid interaction. The gas slip flow in rough microchannels, which
      is characterized by Poiseuille number and mass flow rate, is evaluated and
      compared with smooth microchannels. The effects of roughness height, surface
      fractal dimension, and Knudsen number on slip behavior of gas flow in
      microchannels are all investigated and discussed. The results indicate that the
      presence of surface roughness reduces boundary slip for gas flow in microchannels
      with respect to a smooth surface. The gas flows at the valleys of rough walls are
      no-slip while velocity slips are observed over the top of rough walls. We find
      that the gas flow behavior in rough microchannels is insensitive to the surface
      topography irregularity (unlike the liquid flow in rough microchannels) but is
      influenced by the statistical height of rough surface and rarefaction effects. In
      particular, decrease in roughness height or increase in Knudsen number can lead
      to large wall slip for gas flow in microchannels.

PMID- 23005538
TI  - Upscaling energy concentration in multifrequency single-bubble sonoluminescence
      with strongly degassed sulfuric acid.
AB  - Single-bubble sonoluminescence (SBSL) was explored under a variety of
      multifrequency excitations. In particular, biharmonic excitation was used to
      produce SBSL for unprecedented low dissolved noble gas concentrations in a
      sulfuric acid solution. Reducing the amount of dissolved noble gas makes it
      possible to reach higher acoustic pressures on the SL bubble, which otherwise are
      not attainable because of the Bjerknes instability. By using biharmonic
      excitation, we were able to experimentally trap and to spatially stabilize SL
      bubbles for xenon pressure overhead as low as 1 mbar. As a result, we have access
      to regions in phase space where the plasma temperatures are higher than the ones
      reached before for bubbles driven at ~30 kHz.

PMID- 23005539
TI  - Spatially uniform microflows induced by thermoviscous expansion along a traveling
      temperature wave: analogies with electro-osmotic transport.
AB  - We discover that thermoviscous expansion along a traveling wave in a microfluidic
      channel may be capable of generating a spatially uniform flow profile in a time
      averaged sense. We further delineate that the resultant complex flow
      characteristics, realized by virtue of an intricate interplay between thermal
      compression-expansion waves and temperature-dependent viscosity variations and
      controlled by an external heating, may be remarkably characterized by a unique
      thermal penetration depth scale (analogous to Debye length in electro-osmosis)
      and a velocity scale (analogous to the Helmholtz Smulochowski velocity in electro
      osmosis) that in turn depends on the considerations of "thin" and "thick"
      microchannel limits, as dictated by the thermal penetration depth as compared to
      the lateral extent of the microfluidic channel. We show that, when the thermal
      penetration depth is small as compared to the channel height, a uniform velocity
      profile is generated in the channel in a time-averaged sense. The velocity scale
      characterizing this uniform flow may be represented by a function of the thermal
      diffusivity, volumetric expansion coefficient and thermal viscosity coefficient
      of the fluid, characteristic amplitude and speed of the thermal wave, as well as
      the channel height. Results from the present study are expected to provide
      valuable insights towards arresting hydrodynamic dispersion in microchannels by
      nonelectrochemical means, following a pH-independent route.

PMID- 23005540
TI  - Hot spots in density fingering of exothermic autocatalytic chemical fronts.
AB  - Measurements of two-dimensional (2D) temperature fields are performed by an
      interferometric method during density fingering of the autocatalytic chlorite
      tetrathionate reaction in a Hele-Shaw cell. These measures confirm that, because
      of heat losses through the glass walls of the reactor, the temperature profile
      across the front is a pulse rather than a front. Moreover, the full 2D
      temperature field shows the presence in the reactive zone of hot spots where the
      temperature exceeds the maximum temperature measured in a stable planar front. We
      investigate here experimentally the increase of temperature in the hot spots when
      the composition of the reactants is varied to increase the exothermicity of the
      reaction. We back up these experimental observations by nonlinear simulations of
      a reaction-diffusion-convection model which show that the maximum temperature
      reached in the system depends on the intensity of convection.

PMID- 23005541
TI  - Thermalization and free decay in surface quasigeostrophic flows.
AB  - We derive statistical equilibrium solutions of the truncated inviscid surface
      quasigeostrophic (SQG) equations, and verify the validity of these solutions at
      late times in numerical simulations. The results indicate the pseudoenstrophy
      thermalizes while the pseudoenergy can condense at the gravest modes, in
      agreement with previous indications of a direct cascade of pseudoenstrophy and an
      inverse cascade of pseudoenergy in forced-dissipative SQG systems. At early
      times, the truncated inviscid SQG simulations show a behavior reminiscent of
      forced-dissipative SQG turbulence, and we identify spectral scaling laws for the
      pseudoenergy and pseudoenstrophy spectra. More importantly, a comparison between
      viscous and inviscid simulations allows us to identify free-decay laws for the
      pseudoenstrophy in SQG turbulence at very large Reynolds number.

PMID- 23005542
TI  - Ferrohydrodynamic evaluation of rotational viscosity and relaxation in certain
      ferrofluids.
AB  - A significant effect of aggregation dynamics for aqueous ferrofluid (AF) and
      kerosene based ferrofluid (KF) using magnetic field dependent capillary viscosity
      and magneto-optical relaxation measurements is studied. For better comparison
      parameters of AF and KF are kept similar. Ferrohydrodynamic equations of chain
      forming ferrofluids, dilute ferrofluids, and Brownian dynamic simulations are
      compared. It is observed that the rotational viscosity of AF is larger than that
      of KF due to field induced aggregates in it and strong dipolar interactions. It
      is also observed that at Omegatau ~ 0.04 both AF and KF viscosity becomes almost
      similar, suggesting similar behavior at that shear rate. The magneto-optical
      relaxation in AF exhibits nonexponential behavior when relaxed from higher
      magnetic field and follows irreversible thermodynamics, whereas for KF the
      relaxation is exponential and follows the effective field method. This
      discrepancy is explained based on aggregation dynamics of magnetic particles.
      Results are well described by the corresponding theoretical models.

PMID- 23005543
TI  - Enhanced and reduced heat transport in turbulent thermal convection with polymer
      additives.
AB  - We present an experimental study of turbulent Rayleigh-Benard convection with
      polymer additives made in two convection cells, one with a smooth top and bottom
      plates and the other with a rough top and bottom plates. For the cell with smooth
      plates, a reduction of the measured Nusselt number (Nu) was observed.
      Furthermore, the amount of Nu reduction increases with increasing polymer
      concentration (c), reaching ~12% for c = 120 ppm and an apparent leveling off
      thereafter. For the cell with rough plates, however, an enhancement (~4%) of Nu
      was observed when the polymer concentration is greater than 120 ppm. This
      increase in Nu is corroborated by an increased large-scale circulation (LSC)
      velocity in the same cell when polymers are added. In contrast, the LSC velocity
      in the smooth cell is found to be essentially the same with and without polymers.
      It is further found that in the smooth cell the rms values of the global Nu,
      sigma(Nu), and that of the local temperature, sigma(T), both exhibit similar
      dependence on c as Nu itself. In contrast, sigma(Nu) and sigma(T) in the rough
      cell are found to be essentially independent of c.

PMID- 23005544
TI  - Nonviscous motion of a slow particle in a dust crystal under microgravity
      conditions.
AB  - Subsonic motion of a large particle moving through the bulk of a dust crystal
      formed by negatively charged small particles is investigated using the PK-3 Plus
      laboratory onboard the International Space Station. Tracing the particle
      trajectories shows that the large particle moves almost freely through the bulk
      of the plasma crystal, while dust particles move along characteristic alpha
      shaped pathways near the large particle. In the hydrodynamic approximation, we
      develop a theory of nonviscous dust particle motion about a large particle and
      calculate particle trajectories. Good agreement with experiment validates our
      approach.

PMID- 23005545
TI  - Magnetic moment nonconservation in magnetohydrodynamic turbulence models.
AB  - The fundamental assumptions of the adiabatic theory do not apply in the presence
      of sharp field gradients or in the presence of well-developed magnetohydrodynamic
      turbulence. For this reason, in such conditions the magnetic moment MU is no
      longer expected to be constant. This can influence particle acceleration and have
      considerable implications in many astrophysical problems. Starting with the
      resonant interaction between ions and a single parallel propagating
      electromagnetic wave, we derive expressions for the magnetic moment trapping
      width DeltaMU (defined as the half peak-to-peak difference in the particle
      magnetic moments) and the bounce frequency omega(b). We perform test-particle
      simulations to investigate magnetic moment behavior when resonance overlapping
      occurs and during the interaction of a ring-beam particle distribution with a
      broadband slab spectrum. We find that the changes of magnetic moment and changes
      of pitch angle are related when the level of magnetic fluctuations is low,
      deltaB/B(0) = (10(-3),10(-2)), where B(0) is the constant and uniform background
      magnetic field. Stochasticity arises for intermediate fluctuation values and its
      effect on pitch angle is the isotropization of the distribution function
      f(alpha). This is a transient regime during which magnetic moment distribution
      f(MU) exhibits a characteristic one-sided long tail and starts to be influenced
      by the onset of spatial parallel diffusion, i.e., the variance <(Deltaz)(2)>
      grows linearly in time as in normal diffusion. With strong fluctuations f(alpha)
      becomes completely isotropic, spatial diffusion sets in, and the f(MU) behavior
      is closely related to the sampling of the varying magnetic field associated with
      that spatial diffusion.

PMID- 23005546
TI  - Stimulated scattering of electromagnetic waves carrying orbital angular momentum
      in quantum plasmas.
AB  - We investigate stimulated scattering instabilities of coherent circularly
      polarized electromagnetic (CPEM) waves carrying orbital angular momentum (OAM) in
      dense quantum plasmas with degenerate electrons and nondegenerate ions. For this
      purpose, we employ the coupled equations for the CPEM wave vector potential and
      the driven (by the ponderomotive force of the CPEM waves) equations for the
      electron and ion plasma oscillations. The electrons are significantly affected by
      the quantum forces (viz., the quantum statistical pressure, the quantum Bohm
      potential, as well as the electron exchange and electron correlations due to
      electron spin), which are included in the framework of the quantum hydrodynamical
      description of the electrons. Furthermore, our investigation of the stimulated
      Brillouin instability of coherent CPEM waves uses the generalized ion momentum
      equation that includes strong ion coupling effects. The nonlinear equations for
      the coupled CPEM and quantum plasma waves are then analyzed to obtain nonlinear
      dispersion relations which exhibit stimulated Raman, stimulated Brillouin, and
      modulational instabilities of CPEM waves carrying OAM. The present results are
      useful for understanding the origin of scattered light off low-frequency density
      fluctuations in high-energy density plasmas where quantum effects are eminent.

PMID- 23005547
TI  - Dimensional transitions in small Yukawa clusters.
AB  - We provide a detailed analysis of structural transitions leading to rapid changes
      in the dimensionality of small Yukawa clusters. These transformations are induced
      by variations in the shape of confinement as well as the screening strength. We
      show that even in the most primitive systems composed of only a few strongly
      interacting particles, the order parameter exhibits a power-law behavior in the
      vicinity of the critical point of the continuous transition. The critical
      exponent gamma = 1/2 is found to be universal in all studied cases, which is
      consistent with the general theory of continuous phase transitions.

PMID- 23005548
TI  - Transient slowing down relaxation dynamics of the supercooled dusty plasma liquid
      after quenching.
AB  - The spatiotemporal evolutions of microstructure and motion in the transient
      relaxation toward the steady supercooled liquid state after quenching a dusty
      plasma Wigner liquid, formed by charged dust particles suspended in a low
      pressure discharge, are experimentally investigated through direct optical
      microscopy. It is found that the quenched liquid slowly evolves to a colder state
      with more heterogeneities in structure and motion. Hopping particles and defects
      appear in the form of clusters with multiscale cluster size distributions. Via
      the structure rearrangement induced by the reduced thermal agitation from the
      cold thermal bath after quenching, the temporarily stored strain energy can be
      cascaded through the network to different newly distorted regions and dissipated
      after transferring to nonlinearly coupled motions with different scales. It leads
      to the observed self-similar multiscale slowing down relaxation with power law
      increases of structural order and structural relaxation time, the similar power
      law decreases of particle motions at different time scales, and the stronger and
      slower fluctuations with increasing waiting time toward the new steady state.

PMID- 23005549
TI  - Electron-ion energy partition when a charged particle slows in a plasma: results.
AB  - This paper concerns plasmas in which the electrons and ions may have different
      temperatures. This is a case that must be examined because nuclear fusion
      processes, such as those that appear in ICF capsules, have ions whose temperature
      runs away from the electron temperature. A fast charged particle traversing a
      plasma--such as the alpha particle created in deuterium-tritium fusion--loses its
      energy to both the electrons and the ions in the plasma. In this paper, we
      present and discuss the results for the energy partition, the fractions E(e)/E(0)
      and E(I)/E(0) of the initial energy E(0) of this projectile particle that are
      deposited into the electrons and ions when it has slowed to its minimum energy
      distribution. The calculations, performed in the following paper [Brown, Preston,
      and Singleton Jr., Phys. Rev. E 86, 016407 (2012)], use a well-defined Fokker
      Planck equation for the phase-space distribution of the charged projectiles in a
      weakly to moderately coupled plasma. The Fokker-Planck equation holds to first
      subleading order in the dimensionless plasma coupling constant, which translates
      to computing to order n ln n (leading) and n (subleading) in the plasma density
      n. We present an examination of the energy partition for the general case, in
      which the temperatures of the ions and electrons in the background plasma are not
      equal. The energy partitions for a background plasma in thermal equilibrium have
      been previously computed, but the order n terms have not been calculated, only
      estimated. Our Fokker-Planck formulation provides an unambiguous, precise
      definition of the energy fractions.

PMID- 23005550
TI  - Electron-ion energy partition when a charged particle slows in a plasma: theory.
AB  - The preceding paper [Brown, Preston, and Singleton Jr., Phys. Rev. E 86, 016406
      (2012)] presented precise results for the partition of the initial energy E(0) of
      a fast particle into the ions and electrons--E(I)/E(0) and E(e)/E(0)--when the
      fast particle slows in a plasma whose ion and electron temperatures may differ.
      As emphasized in that paper, this is an important problem because nuclear fusion
      reactions, such as those that occur in an inertial confinement fusion capsule,
      involve ion temperatures that run away from the electron temperatures. As also
      noted in the preceding paper, a precise evaluation entails the use of a well
      defined Fokker-Planck equation for the phase-space evolution of initially fast
      projectile particles. When the plasma has differing ion and electron
      temperatures, the projectiles must slow into a "schizophrenic" final ensemble of
      particles that has neither the electron nor the ion temperature. This is not a
      simple Maxwell-Boltzmann distribution since the electrons are not in thermal
      equilibrium with the ions. Thus, detailed calculations are required for the
      solution of the problem. These we provide here for a weakly to moderately coupled
      plasma. The Fokker-Planck equation holds to first subleading order in the
      dimensionless plasma coupling constant, which translates to computing to order n
      ln n (leading) and n (subleading) in the plasma density n. The energy partitions
      for a background plasma in thermal equilibrium have been previously computed, but
      the order n terms have not been calculated, only estimated. The "schizophrenic"
      final ensemble of slowed particles gives a new mechanism to bring the electron
      and ion temperatures together. The rate at which this new mechanism brings the
      electrons and ions in the plasma into thermal equilibrium will be computed.

PMID- 23005551
TI  - Breaking of upper hybrid oscillations in the presence of an inhomogeneous
      magnetic field.
AB  - We present space-time evolution of large-amplitude upper hybrid modes in a cold
      homogeneous plasma in the presence of an inhomogeneous magnetic field. Using the
      method of Lagrange variables, an exact space-time-dependent solution is obtained
      in parametric form. It is found that the magnetic field inhomogeneity causes
      various nonlinearly excited modes to couple, resulting in phase mixing and
      eventual breaking of the initially excited mode. The occurrence of wave breaking
      is seen by the appearance of spikes in the density profile. These results will be
      of relevance to laboratory and space plasma situations in which the external
      magnetic field is inhomogeneous.

PMID- 23005552
TI  - Effects of nonthermal ions and polarization force on dust-acoustic waves in a
      density-varying dusty plasma.
AB  - A rigorous theoretical investigation has been made of the effects of nonthermal
      ions and polarization force (which arises due to the dust density inhomogeneity)
      on the propagation of dust-acoustic (DA) waves in a density-varying unmagnetized
      dusty plasma (consisting of nonthermal ions, Maxwellian electrons, and negatively
      charged mobile dust) by the normal mode analysis. It has been shown that the
      dispersion properties of the DA waves are significantly modified by the presence
      of nonthermal ions and polarization force. It has been also found that the phase
      speed of the DA waves, as well as the dust density perturbation, increases
      (decreases) with the increase of nonthermal ions (polarization force), and that
      the potential associated with the DA waves decreases with the increase of the
      equilibrium dust number density. The implications of our results in the specific
      situation of space environments (dust-ion plasma situation) are also briefly
      discussed.

PMID- 23005553
TI  - Residual Bernstein-Greene-Kruskal-like waves after one-dimensional electron wave
      breaking in a cold plasma.
AB  - A one-dimensional particle in cell simulation of large amplitude plasma
      oscillations is carried out to explore the physics beyond wave breaking in a cold
      homogeneous unmagnetized plasma. It is shown that after wave breaking, all energy
      of the plasma oscillation does not end up as random kinetic energy of particles,
      but some fraction, which is decided by Coffey's wave breaking limit in warm
      plasma, always remains with two oppositely propagating coherent Bernstein-Greene
      Kruskal like modes with supporting trapped particle distributions. The randomized
      energy distribution of untrapped particles is found to be characteristically non
      Maxwellian with a preponderance of energetic particles.

PMID- 23005554
TI  - Flow shear stabilization of rotating plasmas due to the Coriolis effect.
AB  - A radially decreasing toroidal rotation frequency can have a stabilizing effect
      on nonaxisymmetric magnetohydrodynamic (MHD) instabilities. We show that this is
      a consequence of the Coriolis effect that induces a restoring pressure gradient
      force when plasma is perturbed radially. In a rotating cylindrical plasma, this
      Coriolis-pressure effect is canceled by the centrifugal effect responsible for
      the magnetorotational instability. In a magnetically confined toroidal plasma, a
      large aspect ratio expansion shows that only half of the effect is canceled. This
      analytical result is confirmed by numerical computations. When the plasma rotates
      faster toroidally in the core than near the edge, the effect can contribute to
      the formation of transport barriers by stabilizing MHD instabilities.

PMID- 23005555
TI  - Negative-order Korteweg-de Vries equations.
AB  - In this paper, based on the regular Korteweg-de Vries (KdV) system, we study
      negative-order KdV (NKdV) equations, particularly their Hamiltonian structures,
      Lax pairs, conservation laws, and explicit multisoliton and multikink wave
      solutions thorough bilinear Backlund transformations. The NKdV equations studied
      in our paper are differential and actually derived from the first member in the
      negative-order KdV hierarchy. The NKdV equations are not only gauge equivalent to
      the Camassa-Holm equation through reciprocal transformations but also closely
      related to the Ermakov-Pinney systems and the Kupershmidt deformation. The bi
      Hamiltonian structures and a Darboux transformation of the NKdV equations are
      constructed with the aid of trace identity and their Lax pairs, respectively. The
      single and double kink wave and bell soliton solutions are given in an explicit
      formula through the Darboux transformation. The one-kink wave solution is
      expressed in the form of tanh while the one-bell soliton is in the form of sech,
      and both forms are very standard. The collisions of two-kink wave and two-bell
      soliton solutions are analyzed in detail, and this singular interaction differs
      from the regular KdV equation. Multidimensional binary Bell polynomials are
      employed to find bilinear formulation and Backlund transformations, which produce
      N-soliton solutions. A direct and unifying scheme is proposed for explicitly
      building up quasiperiodic wave solutions of the NKdV equations. Furthermore, the
      relations between quasiperiodic wave solutions and soliton solutions are clearly
      described. Finally, we show the quasiperiodic wave solution convergent to the
      soliton solution under some limit conditions.

PMID- 23005556
TI  - Mathieu function solutions for photoacoustic waves in sinusoidal one-dimensional
      structures.
AB  - The photoacoustic effect for a one-dimensional structure, the sound speed of
      which varies sinusoidally in space, is shown to be governed by an inhomogeneous
      Mathieu equation with the forcing term dependent on the spatial and temporal
      properties of the exciting optical radiation. New orthogonality relations,
      traveling wave Mathieu functions, and solutions to the inhomogeneous Mathieu
      equation are found, which are used to determine the character of photoacoustic
      waves in infinite and finite length phononic structures. Floquet solutions to the
      Mathieu equation give the positions of the band gaps, the damping of the acoustic
      waves within the band gaps, and the dispersion relation for photoacoustic waves.
      The solutions to the Mathieu equation give the photoacoustic response of the
      structure, show the space equivalent of subharmonic generation and acoustic
      confinement when waves are excited within band gaps.

PMID- 23005557
TI  - Matrix algorithm for solving Schrodinger equations with position-dependent mass
      or complex optical potentials.
AB  - We represent low dimensional quantum mechanical Hamiltonians by moderately sized
      finite matrices that reproduce the lowest O(10) bound-state energies and wave
      functions to machine precision. The method extends also to Hamiltonians that are
      neither Hermitian nor PT symmetric and thus allows one to investigate whether or
      not the spectra in such cases are still real. Furthermore, the approach is
      especially useful for problems in which a position-dependent mass is adopted, for
      example in effective-mass models in solid-state physics or in the approximate
      treatment of coupled nuclear motion in molecular physics or quantum chemistry.
      The performance of the algorithm is demonstrated by considering the inversion
      motion of different isotopes of ammonia molecules within a position-dependent
      mass model and some other examples of one- and two-dimensional Hamiltonians that
      allow for the comparison to analytical or numerical results in the literature.

PMID- 23005558
TI  - Scarring of Dirac fermions in chaotic billiards.
AB  - Scarring in quantum systems with classical chaotic dynamics is one of the most
      remarkable phenomena in modern physics. Previous works were concerned mostly with
      nonrelativistic quantum systems described by the Schrodinger equation. The
      question remains outstanding of whether truly relativistic quantum particles that
      obey the Dirac equation can scar. A significant challenge is the lack of a
      general method for solving the Dirac equation in closed domains of arbitrary
      shape. In this paper, we develop a numerical framework for obtaining complete
      eigensolutions of massless fermions in general two-dimensional confining
      geometries. The key ingredients of our method are the proper handling of the
      boundary conditions and an efficient discretization scheme that casts the
      original equation in a matrix representation. The method is validated by (1)
      comparing the numerical solutions to analytic results for a geometrically simple
      confinement and (2) verifying that the calculated energy level-spacing statistics
      of integrable and chaotic geometries agree with the known results. Solutions of
      the Dirac equation in a number of representative chaotic geometries establish
      firmly the existence of scarring of Dirac fermions.

PMID- 23005559
TI  - Grand-canonical Monte Carlo method for Donnan equilibria.
AB  - We present a method that enables the direct simulation of Donnan equilibria. The
      method is based on a grand-canonical Monte Carlo scheme that properly accounts
      for the unequal partitioning of small ions on the two sides of a semipermeable
      membrane, and can be used to determine the Donnan electrochemical potential,
      osmotic pressure, and other system properties. Positive and negative ions are
      considered separately in the grand-canonical moves. This violates instantaneous
      charge neutrality, which is usually considered a prerequisite for simulations
      using the Ewald sum to compute the long-range charge-charge interactions. In this
      work, we show that if the system is neutral only in an average sense, it is still
      possible to get reliable results in grand-canonical simulations of electrolytes
      performed with Ewald summation of electrostatic interactions. We compare our
      Donnan method with a theory that accounts for differential partitioning of the
      salt, and find excellent agreement for the electrochemical potential, the osmotic
      pressure, and the salt concentrations on the two sides. We also compare our
      method with experimental results for a system of charged colloids confined by a
      semipermeable membrane and to a constant-NVT simulation method, which does not
      account for salt partitioning. Our results for the Donnan potential are much
      closer to the experimental results than the constant-NVT method, highlighting the
      important effect of salt partitioning on the Donnan potential.

PMID- 23005560
TI  - Method to solve integral equations of the first kind with an approximate input.
AB  - Techniques are proposed for solving integral equations of the first kind with an
      input known not precisely. The requirement that the solution sought for includes
      a given number of maxima and minima is imposed. It is shown that when the
      deviation of the approximate input from the true one is sufficiently small and
      some additional conditions are fulfilled the method leads to an approximate
      solution that is necessarily close to the true solution. No regularization is
      required in the present approach. Requirements on features of the solution at
      integration limits are also imposed. The problem is treated with the help of an
      ansatz proposed for the derivative of the solution. The ansatz is the most
      general one compatible with the above mentioned requirements. The techniques are
      tested with exactly solvable examples. Inversions of the Lorentz, Stieltjes, and
      Laplace integral transforms are performed, and very satisfactory results are
      obtained. The method is useful, in particular, for the calculation of quantum
      mechanical reaction amplitudes and inclusive spectra of perturbation-induced
      reactions in the framework of the integral transform approach.

PMID- 23005562
TI  - Radiative or neutron transport modeling using a lattice Boltzmann equation
      framework.
AB  - In this paper, the lattice Boltzmann equation (LBE)-based framework is used to
      obtain the solution for the linear radiative or neutron transport equation. The
      LBE framework is devised for the integrodifferential forms of these equations
      which arise due to the inclusion of the scattering terms. The interparticle
      collisions are neglected, hence omitting the nonlinear collision term.
      Furthermore, typical representative examples for one-dimensional or two
      dimensional geometries and inclusion or exclusion of the scattering term
      (isotropic and anisotropic) in the Boltzmann transport equation are illustrated
      to prove the validity of the method. It has been shown that the solution from the
      LBE methodology is equivalent to the well-known P(n) and S(n) methods. This
      suggests that the LBE can potentially provide a more convenient and easy approach
      to solve the physical problems of neutron and radiation transport.

PMID- 23005561
TI  - Effect of the forcing term in the multiple-relaxation-time lattice Boltzmann
      equation on the shear stress or the strain rate tensor.
AB  - In this work, the effect of the forcing term (or external force) in the multiple
      relaxation-time lattice Boltzmann equation (MRTLBE) on the shear stress or the
      strain rate tensor is studied theoretically and numerically. Through a Chapman
      Enskog analysis and numerical simulations, we show that the shear stress (or the
      strain rate tensor) derived from the MRTLBE is second-order accurate in space. We
      then examine the influence of the forcing term on the shear stress or the strain
      rate tensor, and demonstrate that the forcing term effect must be included when
      the shear stress or the strain rate tensor is computed with the nonequilibrium
      part of the distribution function.

PMID- 23005563
TI  - Box-covering algorithm for fractal dimension of complex networks.
AB  - The self-similarity of complex networks is typically investigated through
      computational algorithms, the primary task of which is to cover the structure
      with a minimal number of boxes. Here we introduce a box-covering algorithm that
      outperforms previous ones in most cases. For the two benchmark cases tested,
      namely, the E. coli and the World Wide Web (WWW) networks, our results show that
      the improvement can be rather substantial, reaching up to 15% in the case of the
      WWW network.

PMID- 23005564
TI  - High-order thermal lattice Boltzmann models derived by means of Gauss quadrature
      in the spherical coordinate system.
AB  - We use the spherical coordinate system in the momentum space and an appropriate
      discretization procedure to derive a hierarchy of lattice Boltzmann (LB) models
      with variable temperature. The separation of the integrals in the momentum space
      into angular and radial parts allows us to compute the moments of the equilibrium
      distribution function by means of Gauss-Legendre and Gauss-Laguerre quadratures,
      as well as to find the elements of the discrete momentum set for each LB model in
      the hierarchy. The capability of the high-order models in this hierarchy to
      capture specific effects in microfluidics is investigated through a computer
      simulation of Couette flow by using the Shakhov collision term to get the right
      value of the Prandtl number.

PMID- 23005565
TI  - Forcing scheme in pseudopotential lattice Boltzmann model for multiphase flows.
AB  - The pseudopotential lattice Boltzmann (LB) model is a widely used multiphase
      model in the LB community. In this model, an interaction force, which is usually
      implemented via a forcing scheme, is employed to mimic the molecular interactions
      that cause phase segregation. The forcing scheme is therefore expected to play an
      important role in the pseudoepotential LB model. In this paper, we aim to address
      some key issues about forcing schemes in the pseudopotential LB model. First,
      theoretical and numerical analyses will be made for Shan-Chen's forcing scheme
      [Shan and Chen, Phys. Rev. E 47, 1815 (1993)] and the exact-difference-method
      forcing scheme [Kupershtokh et al., Comput. Math. Appl. 58, 965 (2009)]. The
      nature of these two schemes and their recovered macroscopic equations will be
      shown. Second, through a theoretical analysis, we will reveal the physics behind
      the phenomenon that different forcing schemes exhibit different performances in
      the pseudopotential LB model. Moreover, based on the analysis, we will present an
      improved forcing scheme and numerically demonstrate that the improved scheme can
      be treated as an alternative approach to achieving thermodynamic consistency in
      the pseudopotential LB model.

PMID- 23005566
TI  - Self-learning metabasin escape algorithm for supercooled liquids.
AB  - A generic history-penalized metabasin escape algorithm that contains no
      predetermined parameters is presented in this work. The spatial location and
      volume of imposed penalty functions in the configurational space are determined
      in self-learning processes as the 3N-dimensional potential energy surface is
      sampled. The computational efficiency is demonstrated using a binary Lennard
      Jones liquid supercooled below the glass transition temperature, which shows an
      O(10(3)) reduction in the quadratic scaling coefficient of the overall
      computational cost as compared to the previous algorithm implementation.
      Furthermore, the metabasin sizes of supercooled liquids are obtained as a natural
      consequence of determining the self-learned penalty function width distributions.
      In the case of a bulk binary Lennard-Jones liquid at a fixed density of 1.2,
      typical metabasins are found to contain about 148 particles while having a
      correlation length of 3.09 when the system temperature drops below the glass
      transition temperature.

PMID- 23005567
TI  - Broadband computation of the scattering coefficients of infinite arbitrary
      cylinders.
AB  - We employ a time-domain method to compute the near field on a contour enclosing
      infinitely long cylinders of arbitrary cross section and constitution. We
      therefore recover the cylindrical Hankel coefficients of the expansion of the
      field outside the circumscribed circle of the structure. The recovered
      coefficients enable the wideband analysis of complex systems, e.g., the
      determination of the radar cross section becomes straightforward. The
      prescription for constructing such a numerical tool is provided in great detail.
      The method is validated by computing the scattering coefficients for a
      homogeneous circular cylinder illuminated by a plane wave, a problem for which an
      analytical solution exists. Finally, some radiation properties of an optical
      antenna are examined by employing the proposed technique.

PMID- 23005568
TI  - Microscale boundary conditions of the lattice Boltzmann equation method for
      simulating microtube flows.
AB  - The lattice Boltzmann equation (LBE) method has been shown to be a promising tool
      for microscale gas flows. However, few works focus on the microtube flows, and
      there still are some fundamental problems for the LBE to such flows. In this
      paper, a recently proposed axisymmetric LBE with three kinetic boundary
      conditions, i.e., the combination of bounceback and specular reflection scheme,
      the combination of the Maxwell and specular-reflection scheme, and the
      combination of the Maxwell and bounceback scheme, have been investigated in
      detail. By analyzing the micro-Hagen-Poiseuille flow, we observed the discrete
      boundary condition effect and provided a revised boundary scheme to overcome such
      effect near the slip flow regime. Some numerical tests for the micro-Hagen
      Poiseuille have been carried out to validate the analysis, and the numerical
      results of the revised boundary schemes agree well with the analytic solutions
      which confirmed our theoretical analysis. In addition, we also applied the
      revised combination of the Maxwell and bounceback scheme to microtube flow with
      sudden expansion and contraction, the numerical results of the pressure
      distribution and normalized slip velocity agree well with the theoretical ones.

PMID- 23005569
TI  - Modulational instability of a modified Gross-Pitaevskii equation with higher
      order nonlinearity.
AB  - We consider the modulational instability (MI) of Bose-Einstein condensate (BEC)
      described by a modified Gross-Pitaevskii (GP) equation with higher-order
      nonlinearity both analytically and numerically. A new explicit time-dependent
      criterion for exciting the MI is obtained. It is shown that the higher-order term
      can either suppress or enhance the MI, which is interesting for control of the
      system instability. Importantly, we predict that with the help of the higher
      order nonlinearity, the MI can also take place in a BEC with repulsively contact
      interactions. The analytical results are confirmed by direct numerical
      simulations.

PMID- 23005570
TI  - Addendum to "Event-chain Monte Carlo algorithms for hard-sphere systems".
AB  - We extend the event-chain Monte Carlo algorithm from hard-sphere interactions to
      general potentials. This event-driven Monte Carlo algorithm is nonlocal and
      rejection free and allows for the breaking of detailed balance. The algorithm
      uses a discretized potential, but its running speed is asymptotically independent
      of the discretization. We apply the algorithm to two-dimensional soft spheres and
      discuss its possible implementation directly in the continuum limit.

PMID- 23005571
TI  - Mesenchymal stem cells derived from inflamed periodontal ligaments exhibit
      impaired immunomodulation.
AB  - AIM: The purpose of this study was to investigate the immunomodulatory properties
      of periodontal ligament stem cells derived from inflamed periodontal ligament
      tissues. MATERIAL AND METHODS: Periodontal ligament stem cells were identified
      and isolated from healthy or inflamed periodontal ligament tissues. Peripheral
      blood mononuclear cells were cocultured with inflamed or healthy periodontal
      ligament stem cells, and T-lymphocyte proliferation was determined by incubation
      with carboxyfluorescein succinimidyl ester. T-helper cells (Th1/Th2, Th17) and
      regulatory T cells were analysed by flow cytometry. Cytokine profiles in
      supernatants were tested with a cytometric bead array. RESULTS: Compared to
      healthy cells, inflamed periodontal ligament stem cells showed significantly
      diminished inhibition of T-cell proliferation. In cocultures, stimulated
      peripheral blood mononuclear cells showed significantly less induction of
      CD4+CD25+FOXP3+ regulatory T cells and IL-10 secretion in the presence of
      inflamed compared with healthy periodontal ligament stem cells. Furthermore,
      suppression of Th17 differentiation and IL-17 production by inflamed periodontal
      ligament stem cells was significantly lesser than by healthy cells. CONCLUSION:
      This study demonstrated that inflamed periodontal ligament stem cells had
      markedly dysfunctional immunomodulatory properties; this may contribute to an
      imbalanced immune response, acceleration of osteoclastogenesis and inflammatory
      alveolar bone loss in periodontitis.

PMID- 23005572
TI  - Lack of effect of propranolol in the treatment of lymphangioma in two children.
AB  - Vascular lesions such as hemangiomas and lymphangiomas can cause significant
      mortality and morbidity, as well as amblyopia when located in the orbit. Oral
      propranolol can regress infantile hemangioma during infancy and up to 23 months
      of age, but its effect on lymphangioma has not been demonstrated. We present two
      cases of lymphatic malformations treated with oral propranolol. Patient 1 is a 2
      year-old boy with macrocystic bilateral cervical lymphangioma extending to the
      pharynx and larynx and microcystic lymphangioma of the tongue. The patient was
      started on propranolol 2 mg/kg/day starting at 17 months of age, and after 3
      months only a very slight decrease in tongue volume was noted. Patient 2 is a 3.5
      year-old boy with magnetic resonance imaging evidence of right facial complex
      lymphangioma with venous malformation. The patient was placed on oral propranolol
      2 mg/kg/day. After 3 months of treatment, no change in the lesion was noted
      except for a transient decrease in the size of the conjunctival telangiectasia.
      Propranolol 2 mg/kg/day was not effective in treating lymphatic malformations in
      two children, both older than 17 months at the time of treatment.

PMID- 23005573
TI  - Complete mitochondrial genome of the Kikuchi's minnow Aphyocypris kikuchii
      (Teleostei, Cyprinidae).
AB  - We have sequenced the complete mitochondrial genome of the Kikuchi's minnow,
      Aphyocypris kikuchii (Oshima 1919), which is an endemic species to Taiwan. The
      complete mitochondrial genome is 16,601 bp in size, containing 37 genes coding
      for 13 proteins, 2 rRNAs, 22 tRNAs, and 1 control region. It has the typical
      vertebrate mitochondrial gene arrangement. The sequence information could play an
      important role in resolving the conflict on its current taxonomic position and
      preservation of genetic resources for helping conservation of the endangered
      species.

PMID- 23005576
TI  - The relative age effect in European professional soccer: did ten years of
      research make any difference?
AB  - The relative age effect (RAE) refers to an asymmetry in the birth-date
      distribution favouring players born early in the selection year and
      discriminating against participants born later in the year. While the RAE effect
      was initially reported in sport more than two decades ago, there have been few
      attempts to examine whether player selection strategies have changed over time in
      light of our improved understanding of the phenomenon. We compared the birth-date
      distributions of professional soccer players in ten European countries over a 10
      year period involving the 2000-2001 and 2010-2011 competitive seasons,
      respectively. Chi-square goodness-of-fit tests were used to compare differences
      between the observed and expected birth-date distributions across selection
      years. Generally, results indicated no change in the RAE over the past 10 years
      in professional soccer, emphasizing the robust nature of this phenomenon. We
      propose a change in the structure of youth involvement in soccer to reduce the
      impact of the RAE on talent identification and selection.

PMID- 23005574
TI  - Treating alcoholism reduces financial burden on care-givers and increases quality
      adjusted life years.
AB  - AIMS: The study assessed the alcoholism-related financial burden borne by
      informal care-givers and relatives of German alcoholic patients. DESIGN: By using
      an exploratory approach, care-giver burden was assessed both prior to and 12
      months after detoxification and withdrawal. Quality-of-life data for care-givers
      collected during follow-up were used to calculate the number of quality-adjusted
      life years (QALYs) gained by alcoholics' family members while their relatives are
      undergoing treatment. PARTICIPANTS: Forty-eight informal care-givers and
      relatives of alcoholic patients. SETTING: In-patient and out-patient departments
      of three psychiatric university hospitals in Germany. MEASUREMENTS: Expenditures
      of families related directly to the addiction disorder of alcoholic patients,
      quality of life of care-givers, relapses of patients. FINDINGS: Families'
      expenditures related directly to their addicted member's alcoholism decreased
      from an average of ?676.44 per month (or 20.2% of the total pre-tax family
      income) at baseline to an average of ?145.40 per month at 12 months after the
      beginning of treatment. The average time spent caring for the affected family
      member was reduced from 32.3 hours per month to 8.2 hours per month (P = 0.0109),
      and quality-of-life total scores increased from 60.6 to 68.0. The total gain in
      QALYs for family members was 0.108. When weighed against the average cost of the
      alcoholism treatment, the cost of one QALY for care-giving family members was
      ?20,398 on average. CONCLUSIONS: Among the families of German alcoholics who
      receive detoxification, there is a substantial reduction in family expenditures,
      time spent caring and an increase in quality of life at 1 year. These are
      important but often neglected additional measures of the burden on family members
      and also treatment benefits.

PMID- 23005577
TI  - Polymer-incarcerated chiral Rh/Ag nanoparticles for asymmetric 1,4-addition
      reactions of arylboronic acids to enones: remarkable effects of bimetallic
      structure on activity and metal leaching.
AB  - Robust and highly active bimetallic Rh nanoparticle (NP) catalysts, PI/CB Rh/Ag,
      have been developed and applied to the asymmetric 1,4-addition of arylboronic
      acids to enones without leaching of the metals. We found that the structures of
      the bimetallic Rh/Ag catalysts and chiral ligands strongly affect their catalytic
      activity and the amount of metal leaching. PI/CB Rh/Ag could be recycled several
      times by simple operations while keeping high yields and excellent
      enantioselectivities. To show the versatility of the PI/CB Rh/Ag catalyst, a one
      pot, oxidation-asymmetric 1,4-addition reaction of an allyl alcohol and an
      arylboronic acid was demonstrated by combining the PI/CB Rh/Ag catalyst with
      PI/CB Au as an aerobic oxidation catalyst.

PMID- 23005578
TI  - Na3Cd3B(PO4)4: a new noncentrosymmetric borophosphate with zero-dimensional anion
      units.
AB  - A new noncentrosymmetric borophosphate, Na(3)Cd(3)B(PO(4))(4), has been
      successfully synthesized by conventional solid state reaction for the first time.
      It crystallizes in the orthorhombic space group Pmc2(1) with unit cell parameters
      of a = 13.6854(3) A, b = 5.3346(11) A, c = 18.2169(4) A, and Z = 4.
      Na(3)Cd(3)B(PO(4))(4) features zero-dimensional [B(PO(4))(4)](9-) anion units
      with Cd(2+) and Na(+)/Cd(2+) cations located around them, in which the BO(4)
      tetrahedron is surrounded by four PO(4) tetrahedra by sharing the vertexes of O
      atoms. Second harmonic generation (SHG) measurements show that
      Na(3)Cd(3)B(PO(4))(4) exhibits a SHG response 1.1 times larger than that of
      KH(2)PO(4) (KDP) and is phase matchable.

PMID- 23005579
TI  - The effect of implementation intentions on physical activity among obese older
      adults: a randomised control study.
AB  - OBJECTIVES: Physical activity is a key factor for healthy ageing and obesity
      management. The aim of this study was to test the effect of implementation
      intentions (IIs) on physical activity and body weight among inactive obese older
      adults. DESIGN AND MEASURES: At baseline, 101 obese (classes I and II) older
      adults were randomised to an experimental or a control condition. IIs were
      delivered in the experimental condition in addition to the common intervention
      activities. Physical activity (primary outcome) was assessed by means of
      pedometers. The effect of IIs on body weight (secondary outcome) was also
      evaluated. RESULTS: No main effects for IIs were observed for all outcomes (ps >
      0.21). A significant time * condition interaction was observed for the number of
      steps per day (p = 0.01). At the 6-month follow-up, the improvement in physical
      activity was greater among participants in the experimental condition (d = 0.59).
      None of the measured cognitions moderated or mediated IIs. CONCLUSION: RESULTS
      suggest that IIs could be appropriate to favour the maintenance of physical
      activity among inactive obese older adults. However, this technique seems to have
      limited impacts over and above common intervention activities on weight loss.

PMID- 23005580
TI  - The relation of moral emotion attributions to prosocial and antisocial behavior:
      a meta-analysis.
AB  - This meta-analytic review of 42 studies covering 8,009 participants (ages 4-20)
      examines the relation of moral emotion attributions to prosocial and antisocial
      behavior. A significant association is found between moral emotion attributions
      and prosocial and antisocial behaviors (d = .26, 95% CI [.15, .38]; d = .39, 95%
      CI [.29, .49]). Effect sizes differ considerably across studies and this
      heterogeneity is attributed to moderator variables. Specifically, effect sizes
      for predicted antisocial behavior are larger for self-attributed moral emotions
      than for emotions attributed to hypothetical story characters. Effect sizes for
      prosocial and antisocial behaviors are associated with several other study
      characteristics. Results are discussed with respect to the potential significance
      of moral emotion attributions for the social behavior of children and
      adolescents.

PMID- 23005581
TI  - Prevalence of condom use and associated factors among Chinese female
      undergraduate students in Wuhan, China.
AB  - With the increasing prevalence of premarital sex among college students in China,
      our aim was to examine prevalence and determinants of condom use among sexually
      active female undergraduates at 16 university campuses in Wuhan. Questionnaires
      were distributed to 5076 unmarried female undergraduates, recruited using
      randomized cluster sampling by type of university and student major and grade,
      and anonymously completed questionnaires were received from 4769 (94% of
      enrollees). The complex samples logistic regression was used to examine factors
      associated with condom use, yielding odds ratios and 95% confidence intervals. Of
      4769 female students, 863 (18.1%) reported ever having sexual intercourse. Of
      these, 19.8% used a condom in their first sexual encounter, and these students
      were more likely to age 20 or older at first intercourse, and less likely to live
      in countryside during middle school period, and majoring in the arts. Fully 30%
      of those having intercourse reported never or seldom or sometimes using condoms
      in the past 12 months. Students using condoms consistently in the past 12 months
      were more likely majoring in science and technology, to believe that condoms are
      the safest way to prevent STD and unwanted pregnancy, and to have used a condom
      at first intercourse; they were less likely to live in countryside during middle
      school period, and to report multiple sexual partners since initiating sexual
      behavior. These results suggested that a larger subset of Chinese female
      undergraduates is engaged in unprotected, premarital sex, and interventions
      provided for them should stress the importance of delaying sexual initiation,
      using condoms from the very first sexual encounter, and consistently using
      condoms after initiating sex.

PMID- 23005582
TI  - A general class of semiparametric transformation frailty models for
      nonproportional hazards survival data.
AB  - We propose a semiparametrically efficient estimation of a broad class of
      transformation regression models for nonproportional hazards data. Classical
      transformation models are to be viewed from a frailty model paradigm, and the
      proposed method provides a unified approach that is valid for both continuous and
      discrete frailty models. The proposed models are shown to be flexible enough to
      model long-term follow-up survival data when the treatment effect diminishes over
      time, a case for which the PH or proportional odds assumption is violated, or a
      situation in which a substantial proportion of patients remains cured after
      treatment. Estimation of the link parameter in frailty distribution, considered
      to be unknown and possibly dependent on a time-independent covariates, is
      automatically included in the proposed methods. The observed information matrix
      is computed to evaluate the variances of all the parameter estimates. Our
      likelihood-based approach provides a natural way to construct simple statistics
      for testing the PH and proportional odds assumptions for usual survival data or
      testing the short- and long-term effects for survival data with a cure fraction.
      Simulation studies demonstrate that the proposed inference procedures perform
      well in realistic settings. Applications to two medical studies are provided.

PMID- 23005583
TI  - Emotional expression and vocabulary learning in adults and children.
AB  - A great deal of what we know about the world has not been learned via first-hand
      observation but thanks to others' testimony. A crucial issue is to know which
      kind of cues people use to evaluate information provided by others. In this
      context, recent studies in adults and children underline that informants' facial
      expressions could play an essential role. To test the importance of the other's
      emotions in vocabulary learning, we used two avatars expressing happiness, anger
      or neutral emotions when proposing different verbal labels for an unknown object.
      Experiment 1 revealed that adult participants were significantly more likely than
      chance to choose the label suggested by the avatar displaying a happy face over
      the label suggested by the avatar displaying an angry face. Experiment 2 extended
      these results by showing that both adults and children as young as 3 years old
      showed this effect. These data suggest that decision making concerning newly
      acquired information depends on informant's expressions of emotions, a finding
      that is consistent with the idea that behavioural intents have facial signatures
      that can be used to detect another's intention to cooperate.

PMID- 23005584
TI  - Underwater movement times with ongoing visual control.
AB  - Arm movements made in a water environment take longer to perform than in an air
      environment due to the drag forces experienced by the arm. Movement times for
      ballistic underwater movements have been accurately modelled by Hoffmann and Gan
      ( 1988 ). The present work models the movement time for movements that require
      ongoing visual control. In these movements, the 'distance-covering' phase is
      carried out at high speeds and will be affected by the fluid characteristics,
      while the 'homing-in' phase, where speeds are low, is less affected. An
      experiment is reported that models these effects and which indicates that a
      ballistic component needs to be added to the standard Fitts model in order to
      account for the drag forces in the distance-covering phase of the movement.
      PRACTITIONER SUMMARY: Many tasks, such as maintenance and salvage work, require
      work to be done underwater. Times for performing underwater tasks are generally
      longer than on land. This article is one step in modelling the difference in task
      times for land and underwater movements.

PMID- 23005585
TI  - The concept of social justice for our psychiatric nursing practice.

PMID- 23005586
TI  - Caregiver burden in bipolar hypomania and mania: a systematic review.
AB  - PURPOSE:   Bipolar mania is characterized by marked impairment in social,
      occupational, or other important areas of functioning. One should expect to see
      an equally severe burden in informal caregivers. The literature was reviewed in
      order to provide a foundation upon which to build nursing interventions.
      CONCLUSIONS:   Several characteristics of bipolar mania-patient aggressiveness,
      lack of insight, and financial problems-were identified as severe burdens to
      caregivers. Professionals might not have a total view of the extent of the burden
      in caregivers. This review could not link the patients' mania or hypomania to
      factors that were described in other literature on caregiver burden related to
      bipolar disorder, regardless of the type of episode. PRACTICE IMPLICATIONS:  
      There is a need for further research in this area to make more explicit the
      burden on caregivers during times of mania or hypomania.

PMID- 23005587
TI  - Which nontraditional outcomes should be measured in healthcare decision-making in
      schizophrenia? A systematic review.
AB  - PURPOSE:   This article aims to define the utility of nontraditional outcomes
      (NTOs) in healthcare decision-making in schizophrenia. DESIGN AND METHODS:   A
      systematic review of studies published between January 1, 1996, and December 31,
      2008, was performed. A 10-point evidence-based utility index (UI) was used to
      assess the utility of NTOs: high (UI: 7.5-10), medium (UI: >= 5 to <7.5), and low
      (UI: <5) utility. FINDINGS:   Of 736 citations identified, 94 met inclusion
      criteria. One hundred ninety-four NTOs were identified (patient reported outcomes
      [38.7%] and economic outcomes [61.3%]). Of these, 68 (35.1%) were appropriate for
      decision making. PRACTICE IMPLICATIONS:   Numerous NTOs with low utility in
      schizophrenia are being used for healthcare policy and clinical care by policy
      makers, managers, and healthcare professionals. Medium and low utility NTOs
      should be used with caution.

PMID- 23005588
TI  - Nursing care of the adoption triad.
AB  - PURPOSE: This study describes the practice settings and interventions of nurses
      who care for members of the adoption triad (AT; birth parents, adoptive parents,
      child). DESIGN AND METHODS: A 28-item, descriptive, cross-sectional survey was
      used. FINDINGS: Ninety-seven (97) nurses provided complete (65) or partial (32)
      responses. Most frequently reported practice settings were labor, delivery or
      postpartum unit, and pediatrics. Assessed needs varied by AT members. However,
      interventions for all members of the triad included emotional support and
      therapeutic communication. PRACTICE IMPLICATIONS: The unique placement of
      advanced practice nurses in various clinical settings allows for contact with
      members of the AT in vulnerable and crisis periods.

PMID- 23005589
TI  - Effectiveness of antenatal emotional self-management training program in
      prevention of postnatal depression in Chinese women.
AB  - PURPOSE: This study aimed to study the effectiveness of an emotional self
      management training program to antenatal women in the prevention of postnatal
      depression. DESIGN AND METHODS: The sample comprised 240 women who were at 32
      weeks antenatal. They were randomly assigned into the intervention group and the
      control group. FINDINGS: On completion of the program, the intervention group
      reported significantly lower mean Patient Health Questionnaire-9 and Edinburgh
      Postnatal Depression Scale scores than the control group. Fewer participants from
      the intervention group were diagnosed as having postnatal depression using the
      Structured Clinical Interview for DSM-IV. PRACTICE IMPLICATIONS: An antenatal
      emotional self-management training that may lower the risk of developing
      postnatal depression among Chinese women is recommended.

PMID- 23005590
TI  - Understanding content and process: guidelines for group leaders.
AB  - PURPOSE: To discuss basic concepts of group therapy as a treatment modality.
      CONCLUSIONS: The psychiatric nurse group leader uses concepts of content and
      process at his/her disposal as powerful tools of change, adaptation, and
      recovery. PRACTICE IMPLICATIONS: Group therapy is a common modality in treating
      mental disorders that is both evidence based and cost-effective. Group therapy is
      practiced in inpatient, outpatient, partial hospitalization, and residential
      treatment facilities. Because of their understanding of the bio-psycho-social
      origin of mental illness, psychiatric nurses are uniquely prepared to assist in
      many roles as facilitators of change.

PMID- 23005591
TI  - Cancer genomics and pathology: all together now.
AB  - Cancer develops from a single cell with stepwise accumulation of genomic
      alterations. Recent innovative sequencing technologies have made it possible to
      sequence the full cancer genome. Cancer genome sequencing has been productive and
      helpful in the discovery of novel cancer genes. It also has revealed previously
      unknown but intriguing features of the cancer genome such as chromothripsis and
      kataegis. However, careful comparison of these studies has suggested that
      analyses of most tumors still seem to be incomplete, and histopathological
      diagnosis/classification will be essential for refining these data. Based on the
      improvement of technology and the completion of the cancer gene catalog, genetic
      diagnosis, such as examination of all potentially druggable mutations, of
      individual cancers will be performed routinely together with histological
      diagnosis. Pathologists will play a central role in both interpreting these patho
      molecular diagnoses for oncologists, and the process of decision-making necessary
      for individualized medicine.

PMID- 23005592
TI  - Diabetic mastopathy, a clinicopathological correlation of 34 cases.
AB  - Diabetic mastopathy (DM) is an unusual fibrous disease of the breast. We report
      34 cases with clinicopathological correlation and follow-ups. Patients mean age
      was 57 years and 24 had histories of diabetes mellitus. The DM presented as a
      palpable breast mass in 85.3% of the cases clinically. Image findings were often
      as an irregular hypoechoic mass (44.4%) on ultrasound and negative or non
      specific density (67.6%) on mammogram. Histologically, we found that the majority
      of DM occurred in the upper outer/central part of the breast (76%) and the size
      ranged from 0.5 to 3.7 cm. All cases showed lymphocytic lobulitis and vasculitis,
      keloidal fibrosis, lobular atrophy and varying degree of epithelioid fibroblasts.
      Examining the surrounding normal tissue of the excision specimens revealed that
      the margins of DM were often poorly circumscribed and irregularly demarcated from
      the sounding breast tissue. Vascular calcifications were identified in 10 of 24
      excisional specimens, suggesting a hypothesis that vascular damage and
      scar/wounding healing process could contribute to the pathogenesis of DM. Twenty
      one cases had repeated procedures for uncertain descriptive diagnosis. This is
      the largest study of diabetic mastopathy to date with clinical and imagining
      correlation. Recognition of this benign entity is important to better
      understanding the pathogenesis and to avoid unnecessary procedures.

PMID- 23005593
TI  - The characteristic expression of B7-H3 and B7-H4 in liver biopsies from patients
      with HBV-related acute-on-chronic liver failure.
AB  - Hepatitis B virus (HBV) is a major public health problem, and HBV-related acute
      on-chronic liver failure (HBV-ACLF) has an extremely poor prognosis due to a lack
      of effective treatments. B7-H3 and B7-H4 are two novel members of the B7
      superfamily that are actively involved in regulating the pathogenesis of
      infectious diseases. However, the intrahepatic expression of both members in HBV
      ACLF patients has yet to be described. In this study, we analyzed the expression
      of B7-H3 and B7-H4 in HBV-ACLF biopsies by immunohistochemistry. Our results
      showed that both members were observed in all HBV-ACLF samples, and their
      expression was chiefly observed on infiltrating inflammatory cells and the
      damaged bile ducts. Immunofluorescence double staining showed that B7-H4 was
      expressed chiefly on CD3(+)  T cells, CD68(+)  macrophages, CK-18(+)  bile ducts,
      and CD31(+)  endothelial cells, while B7-H3 was found on all cell types detected.
      The expression of the programmed death (PD)-1 ligands, PD-L1 and PD-L2, was also
      detected in these liver tissues and they were found to be co-expressed with B7-H3
      and B7-H4. These results suggest that the B7-family signaling is most likely to
      affect the pathogenesis of this disease, and a clear understanding of their
      functional roles may further elucidate the disease process.

PMID- 23005594
TI  - Expression of macrophage-derived chemokine (CCL22) in atherosclerosis and
      regulation by histamine via the H2 receptor.
AB  - Macrophage-derived chemokine (CCL22) is a member of the CC-family of chemokines
      and is synthesized by monocyte-derived macrophages and dendritic cells (DCs). In
      this study, we investigate the relationship between monocytes/macrophages and
      histamine in atherosclerosis and discover that histamine levels regulate various
      immunologically important molecules and influences atherosclerotic progression.
      Immunohistochemical analysis of human atherosclerotic lesions revealed that
      macrophages and DCs express CCL22. The human acute monocytic leukemia cell line
      (THP-1) adhered to culture plates and morphologically changed to macrophage-like
      cells when treated with tetradecanoylphorbol-13-acetate (TPA). Macrophage-like
      cells derived from THP-1 cells and cultivated peripheral blood mononuclear cells
      (PBMCs) show similar expression of CCL22. Gene expression of CCL22 was also
      detected in THP-1 cells treated with histamine and the expression of the protein
      produced by the CCL22 gene is similar in PBMCs and THP-1 cells. In addition, the
      histamine H2 receptor mediated these reactions. Our results suggest that CCL22
      expression in monocytes is regulated by histamine, and that CCL22 is involved
      centrally in the development of human atherosclerotic lesions. In conclusion,
      CCL22 is a marker that is a characteristic of the monocytes/ macrophages
      migrating into atherosclerotic lesions and histamine plays a role in regulating
      its expression.

PMID- 23005595
TI  - High expression of ALDH1 and SOX2 diffuse staining pattern of oral squamous cell
      carcinomas correlates to lymph node metastasis.
AB  - One of the major factors involved in the prognosis of oral squamous cell
      carcinoma (OSCC) patients is metastasis. Recent progress in cancer stem-like
      cell/cancer-initiating cell (CSC/CIC) research indicates that CSCs are related to
      metastasis. Aldehyde dehydrogenase 1 - (ALDH1) and SRY-related HMG-box gene 2
      (SOX2) have recently been shown to be putative CSC markers for several human
      malignancies. The aim of this study was to determine the association of ALDH1 and
      SOX2 expression in oral squamous cell carcinoma (OSCC) with lymph node
      metastasis. Immunohistochemical staining of ALDH1, SOX2 and Ki67 was performed in
      80 OSCC tissues. High expression rates of ALDH1 (2%-40%) were found to be related
      to lymph node metastasis (P = 0.0017). Interestingly, we found that SOX2 staining
      could be classified into two patterns: (i) peripheral staining pattern; and (ii)
      diffuse staining pattern. The diffuse staining pattern showed a significant
      correlation with lymph node metastasis (P < 0.001). No correlation was found
      between Ki67 staining and lymph node metastasis (P = 0.4724). The ALDH1 positive
      staining rates in metastatic lymph nodes were higher than that in corresponding
      primary OSCC tissues. These results indicate that high expression rates of ALDH1
      and SOX2 diffuse staining patterns might be novel prediction markers for OSCC
      lymph node metastasis.

PMID- 23005596
TI  - Clinicopathological analysis of a composite lymphoma containing both T- and B
      cell lymphomas.
AB  - Composite lymphomas (CLs) have been reported in 1-4.7% of all lymphomas, however,
      CLs containing both T- and B-cell lymphomas (CTBLs) are very rare. Here, we
      examined the clinical and pathological features of 29 CTBLs. These CTBLs included
      21 patients with angioimmunoblastic T-cell lymphoma (AITL) and diffuse large B
      cell lymphoma (DLBCL), two with adult T-cell leukemia/lymphoma and DLBCL, one
      with AITL and Follicular lymphoma, one with Lennert lymphoma and DLBCL, one with
      subcutaneous panniculitis-like T-cell lymphoma and DLBCL, one with peripheral T
      cell lymphoma (PTCL) and DLBCL, one with cutaneous T-cell lymphoma and DLBCL, and
      one with PTCL and chronic lymphocytic leukemia. Eighteen of 27 patients (67%)
      were shown to be Epstein-Barr virus (EBV)-encoded RNA-positive in their B-cell
      lymphoma component. T-cell and B-cell clonality were confirmed by flow cytometry,
      Southern blot analysis, and/or polymerase chain reaction (PCR). Using Southern
      blot analysis, clonal immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)
      rearrangements were detected in 11 of 21 and 15 of 24 cases, respectively. Using
      PCR analysis, clonal IgH and TCR rearrangements were detected in 7 of 8 and 7 of
      7 Southern blot-negative cases, respectively. Our results suggested that PCR
      analysis was useful in diagnosing CTBL.

PMID- 23005597
TI  - Multiple carcinoid tumors of the rectum: report of two cases suggesting the
      origin of carcinoid tumors.
AB  - Two cases of multiple carcinoid tumors of the rectum with numerous micronests of
      carcinoid tumors are reported. The patients were 51- and 58-year-old males. Many
      carcinoid tumors and numerous carcinoid micronests were found in the resected
      rectum; the total number of carcinoid tumors, groups of micronests, and solitary
      micronests was 69 in the first case and 62 in the second case. The micronests,
      consisting of a few to many endocrine cells, were observed in the lamina propria,
      muscularis mucosa, and/or submucosa. Micronests increased in number, gathered and
      formed carcinoid tumors, which were up to 8 mm in diameter. It was found that a
      nest of the carcinoid tumors in the lamina propria showed continuity with the
      endocrine cells of a crypt in the different carcinoid tumors in both cases. The
      carcinoid tumor and micronest infiltrated the nerves and ganglions in the
      muscularis mucosa and submucosa. Nests of the carcinoid tumors and micronests
      were surrounded by S-100-positive cells. Lymph node metastases of the carcinoid
      tumor were found in both cases. Rectal carcinoid tumors may originate from
      endocrine cells of the crypts, and multiple carcinoid tumors may occur
      heterogeneously.

PMID- 23005598
TI  - Plexiform perineurioma of the lip: a case report and review of literature.
AB  - We describe a plexiform perineurioma, which is an extremely rare variant of soft
      tissue perineurioma. A 43-year-old Japanese man presented with a painless, well
      demarcated, elastic, soft tumor measuring 2.0 * 1.9 cm on the upper lip that had
      persisted for three years. Microscopically, a plexiform tumor composed of
      minimally atypical spindle cells with wavy nuclei was located in the lamina
      propria of the oral mucosa. Tumor cells were concentrically arranged around small
      vessels and aligned in parallel with delicate collagen fibers on a fibromyxoid
      background in the hypocellular area. Tumor cells were immunohistochemically
      positive for EMA, GLUT-1, claudin-1, and CD34 and negative for S-100 protein. The
      histopathological and immunohistochemical profiles of the excised tumor indicated
      a diagnosis of plexiform perineurioma. The patient has remained free of
      recurrence for sixteen months. Intraoral soft tissue perineurioma is rare and two
      of the four reported plexiform perineuriomas, including that described herein,
      notably involved the intraoral area. According to previous reports, plexiform
      perineuriomas largely develop in middle-aged women without a history of type 1 or
      type 2 neurofibromatosis. The clinical courses of all reported plexiform
      perineuriomas have been benign.

PMID- 23005599
TI  - Case reports of primary pulmonary adenocarcinoma with pleural spread: so-called
      pseudomesotheliomatous adenocarcinoma.
AB  - We report two autopsy cases of primary pulmonary adenocarcinoma associated with
      unusual pleural spread. Both patients had confirmed history of asbestos exposure.
      In the first patient the tumor was localized in one pulmonary lobe with marked
      infiltration into pleura, chest wall and diaphragm. In the second patient the
      entire right lung was covered by irregularly thickened tumor. Both tumors were
      mainly located in the extrapulmonary area and the intrapulmonary portions
      represented only minor components. Histologically, tumor cells demonstrated
      glandular and papillary growth patterns associated with focal hobnail-like
      features. Immunohistochemical evaluation revealed diffuse and marked
      immunoreactivity of TTF-1, CEA, CD15 and MOC31 in both cases, while calretinin,
      CK5/6, vimentin, thrombomodulin and HBME-1 were broadly positive in one case. D2
      40 was not detected in either case. Examination using electron microscopy
      revealed the presence of sparse and short microvilli in tumor cells. All of the
      above findings are consistent with adenocarcinoma of the lung. Primary
      adenocarcinoma with a characteristic pleural extention grossly resembling
      malignant mesothelioma has been previously reported in the literature as
      pseudomesotheliomatous adenocarcinoma. This is the first report of
      pseudomesotheliomatous adenocarcinoma displaying variable immunoprofile with a
      diagnosis using electron microscopical examination. Additionally, we performed
      quantitative analysis of asbestos bodies in pseudomesotheliomatous
      adenocarcinoma.

PMID- 23005600
TI  - Gastric nodular lesion caused by IgG4-related disease.

PMID- 23005601
TI  - Local field effects in the energy transfer between a chromophore and a carbon
      nanotube: a single-nanocompound investigation.
AB  - Energy transfer in noncovalently bound porphyrin/carbon nanotube compounds is
      investigated at the single-nanocompound scale. Excitation spectroscopy of the
      luminescence of the nanotube shows two resonances arising from intrinsic
      excitation of the nanotube and from energy transfer from the porphyrin.
      Polarization diagrams show that both resonances are highly anisotropic, with a
      preferred direction along the tube axis. The energy transfer is thus strongly
      anisotropic despite the almost isotropic absorption of porphyrins. We account for
      this result by local field effects induced by the large optical polarizability of
      nanotubes. We show that the local field correction extends over several
      nanometers outside the nanotubes and drives the overall optical response of
      functionalized nanotubes.

PMID- 23005602
TI  - Shiftwork and higher pancreatic secretion: early detection of an intermediate
      state of insulin resistance?
AB  - Previous studies have suggested that shiftwork can affect the prevalence of
      metabolic syndrome. This is thought to be related to disturbance of lipid
      parameters rather than their effects on glucose metabolism. Several complex
      mechanisms are suspected to be involved and notably insulin resistance, though
      the available data are limited. The objective of the present study was to provide
      further evidence for the effects of shiftwork on glucose and lipid metabolism
      with a specific focus on insulin resistance. A cross-sectional study has
      recruited 97 shiftworkers (SWs) (three shifts, 8 h) and 95 strictly day workers
      (DWs) from the same plant for 2001-2002. Several indices of insulin sensitivity
      or resistance were calculated, based on formulas of the homeostasis model
      assessment for insulin resistance (HOMA-IR), the Revised-Quicki, McAuley and
      Disse indices. The HOMA-beta-cell index was used as a reflection of pancreatic
      secretion. Characteristics of the occupation, habitual diet and lifestyles were
      recorded. Logistic regression analysis in which pancreatic function or insulin
      sensitivity was the dependent variable was used to compare alternative models.
      RESULTS: SWs were characterized as having significantly higher triglycerides and
      free fatty acids and normal but lower blood glucose. The risk of a high beta-cell
      activity was increased almost three-fold in SWs. By adjusting for many
      confounding factors, SWs had significantly lower insulin sensitivity according to
      several indices, whereas HOMA-IR was not meaningfully different between shift and
      DWs. Lower insulin sensitivity and a compensatory pancreas response to maintain a
      normal glucose tolerance may suggest an intermediate state before development of
      frank insulin resistance in SWs. Early detection of these moderate alterations of
      the insulin/glucose balance could be important in the prevention of diabetes.

PMID- 23005603
TI  - Enantioselective route to ketones and lactones from exocyclic allylic alcohols
      via metal and enzyme catalysis.
AB  - A general and efficient route for the synthesis of enantiomerically pure alpha
      substituted ketones and the corresponding lactones has been developed. Ruthenium-
      and enzyme-catalyzed dynamic kinetic resolution (DKR) with a subsequent Cu
      catalyzed alpha-allylic substitution are the key steps of the route. The alpha
      substituted ketones were obtained in high yields and with excellent enantiomeric
      excess. The methodology was applied to the synthesis of a naturally occurring
      caprolactone, (R)-10-methyl-6-undecanolide, via a subsequent Baeyer-Villiger
      oxidation.

PMID- 23005604
TI  - Vacuum instability and pair production in an optical setting.
AB  - In the Dirac-sea picture, the physics of pair production and instability of the
      quantum electrodynamics vacuum in presence of an oscillating electric field
      resembles the phenomenon of interband transition of light waves in photonic
      superlattices induced by a geometric curvature. We realize a binary wave guide
      superlattice with a curved optical axis mimicking dynamical pair production
      induced by two counterpropagating ultrastrong laser pulses. Our optical analogue
      enables visualization of formation of electron-positron pair in physical space as
      splitting of a wave packet, originally representing an electron in the Dirac sea.

PMID- 23005605
TI  - Epistemic view of quantum states and communication complexity of quantum
      channels.
AB  - The communication complexity of a quantum channel is the minimal amount of
      classical communication required for classically simulating a process of state
      preparation, transmission through the channel and subsequent measurement. It
      establishes a limit on the power of quantum communication in terms of classical
      resources. We show that classical simulations employing a finite amount of
      communication can be derived from a special class of hidden variable theories
      where quantum states represent statistical knowledge about the classical state
      and not an element of reality. This special class has attracted strong interest
      very recently. The communication cost of each derived simulation is given by the
      mutual information between the quantum state and the classical state of the
      parent hidden variable theory. Finally, we find that the communication complexity
      for single qubits is smaller than 1.28 bits. The previous known upper bound was
      1.85 bits.

PMID- 23005606
TI  - Quantum coherence and sensitivity of avian magnetoreception.
AB  - Migratory birds and other species have the ability to navigate by sensing the
      geomagnetic field. Recent experiments indicate that the essential process in the
      navigation takes place in the bird's eye and uses chemical reaction involving
      molecular ions with unpaired electron spins (radical pair). Sensing is achieved
      via geomagnetic-dependent dynamics of the spins of the unpaired electrons. Here
      we utilize the results of two behavioral experiments conducted on European robins
      to argue that the average lifetime of the radical pair is of the order of a
      microsecond and therefore agrees with experimental estimations of this parameter
      for cryptochrome--a pigment believed to form the radical pairs. We also find a
      reasonable parameter regime where the sensitivity of the avian compass is
      enhanced by environmental noise, showing that long coherence time is not required
      for navigation and may even spoil it.

PMID- 23005607
TI  - Criticality and strong intermittency in the Lorentz channel.
AB  - We demonstrate the emergence of criticality due to power-law cross correlations
      in an ensemble of noninteracting particles propagating in an infinite Lorentz
      channel. The origin of these interparticle long-range correlations is the
      intermittent dynamics associated with the ballistic corridors in the single
      particle phase space. This behavior persists dynamically, even in the presence of
      external driving, provided that the billiard's horizon becomes infinite at
      certain times. For the driven system, we show that Fermi acceleration permits the
      synchronization of the particle motion with the periodic appearance of the
      ballistic corridors. The particle ensemble then acquires characteristics of self
      organization as the weight of the phase space regions leading to critical
      behavior increases with time.

PMID- 23005608
TI  - Long-time behavior of the momentum distribution during the sudden expansion of a
      spin-imbalanced Fermi gas in one dimension.
AB  - We study the sudden expansion of spin-imbalanced ultracold lattice fermions with
      attractive interactions in one dimension after turning off the longitudinal
      confining potential. We show that the momentum distribution functions of majority
      and minority fermions quickly approach stationary values due to a quantum
      distillation mechanism that results in a spatial separation of pairs and majority
      fermions. As a consequence, Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) correlations
      are lost during the expansion. Furthermore, we argue that the shape of the
      stationary momentum distribution functions can be understood by relating them to
      the integrals of motion in this integrable quantum system. We discuss our results
      in the context of proposals to observe FFLO correlations, related to recent
      experiments by Liao et al., Nature (London) 467, 567 (2010).

PMID- 23005609
TI  - Spectroscopy of the Schwarzschild black hole at arbitrary frequencies.
AB  - Linear field perturbations of a black hole are described by the Green function of
      the wave equation that they obey. After Fourier decomposing the Green function,
      its two natural contributions are given by poles (quasinormal modes) and a
      largely unexplored branch cut in the complex frequency plane. We present new
      analytic methods for calculating the branch cut on a Schwarzschild black hole for
      arbitrary values of the frequency. The branch cut yields a power-law tail decay
      for late times in the response of a black hole to an initial perturbation. We
      determine explicitly the first three orders in the power-law and show that the
      branch cut also yields a new logarithmic behavior T(-2l-5)lnT for late times.
      Before the tail sets in, the quasinormal modes dominate the black hole response.
      For electromagnetic perturbations, the quasinormal mode frequencies approach the
      branch cut at large overtone index n. We determine these frequencies up to n(
      5/2) and, formally, to arbitrary order. Highly damped quasinormal modes are of
      particular interest in that they have been linked to quantum properties of black
      holes.

PMID- 23005610
TI  - Density of states in gauge theories.
AB  - The density of states is calculated for the SU(2), SU(3), and a compact U(1)
      lattice gauge theories using a modified version of the Wang-Landau algorithm. We
      find that the density of states of the SU(2) gauge theory can be reliably
      calculated over a range of 120,000 orders of magnitude for lattice sizes as big
      as 20(4). We demonstrate the potential of the algorithm by reproducing the SU(2)
      average action, its specific heat, and the critical couplings of the weak first
      order transition in U(1).

PMID- 23005611
TI  - Long-range magnetic fields in the ground state of the Standard Model plasma.
AB  - In thermal equilibrium the ground state of the plasma of Standard Model particles
      is determined by temperature and exactly conserved combinations of baryon and
      lepton numbers. We show that at nonzero values of the global charges a
      translation invariant and homogeneous state of the plasma becomes unstable and
      the system transits into a new equilibrium state, containing a large-scale
      magnetic field. The origin of this effect is the parity-breaking character of
      weak interactions and chiral anomaly. This situation could occur in the early
      Universe and may play an important role in its subsequent evolution.

PMID- 23005612
TI  - Measurement of the difference in CP-violating asymmetries in D(0)->K(+)K(-) and
      D(0)->pi(+)pi(-) decays at CDF.
AB  - We report a measurement of the difference (DeltaA(CP)) between time-integrated CP
      violating asymmetries in D(0)->K(+)K(-) and D(0)->pi(+)pi(-) decays reconstructed
      in the full data set of proton-antiproton collisions collected by the Collider
      Detector at Fermilab, corresponding to 9.7  fb(-1) of integrated luminosity. The
      strong decay D(*+)->D(0)pi(+) is used to identify the charm meson at production
      as D(0) or D[over -](0). We measure DeltaA(CP)=[-0.62+/-0.21(stat)+/
      0.10(syst)]%, which differs from zero by 2.7 Gaussian standard deviations. This
      result supports similar evidence for CP violation in charm-quark decays obtained
      in proton-proton collisions.

PMID- 23005614
TI  - Search for the standard model Higgs boson decaying to a bb pair in events with
      two oppositely charged leptons using the full CDF data set.
AB  - We present a search for the standard model Higgs boson produced in association
      with a Z boson in data collected with the CDF II detector at the Tevatron,
      corresponding to an integrated luminosity of 9.45  fb(-1). In events consistent
      with the decay of the Higgs boson to a bottom-quark pair and the Z boson to
      electron or muon pairs, we set 95% credibility level upper limits on the ZH
      production cross section times the H->bb branching ratio as a function of Higgs
      boson mass. At a Higgs boson mass of 125  GeV/c(2), we observe (expect) a limit
      of 7.1 (3.9) times the standard model value.

PMID- 23005619
TI  - Complete tenth-order QED contribution to the muon g-2.
AB  - We report the result of our calculation of the complete tenth-order QED terms of
      the muon g-2. Our result is a(MU)((10))=753.29 (1.04) in units of (alpha/pi)(5),
      which is about 4.5 s.d. larger than the leading-logarithmic estimate 663(20). We
      also improve the precision of the eighth-order QED term of a(MU), obtaining
      a(MU)((8))=130.8794 (63) in units of (alpha/pi)(4). The new QED contribution is
      a(MU)(QED)=116,584,718,951 (80)*10(-14), which does not resolve the existing
      discrepancy between the standard-model prediction and measurement of a(MU).

PMID- 23005613
TI  - Combined search for the standard model Higgs boson decaying to a bb pair using
      the full CDF data set.
AB  - We combine the results of searches for the standard model (SM) Higgs boson based
      on the full CDF Run II data set obtained from sqrt[s]=1.96  TeV pp collisions at
      the Fermilab Tevatron corresponding to an integrated luminosity of 9.45  fb(-1).
      The searches are conducted for Higgs bosons that are produced in association with
      a W or Z boson, have masses in the range 90-150  GeV/c(2), and decay into bb
      pairs. An excess of data is present that is inconsistent with the background
      prediction at the level of 2.5 standard deviations (the most significant local
      excess is 2.7 standard deviations).

PMID- 23005618
TI  - Tenth-order QED contribution to the electron g-2 and an improved value of the
      fine structure constant.
AB  - This letter presents the complete QED contribution to the electron g-2 up to the
      tenth order. With the help of the automatic code generator, we evaluate all
      12,672 diagrams of the tenth-order diagrams and obtain 9.16 (58)(alpha/pi)(5). We
      also improve the eighth-order contribution obtaining -1.9097 (20)(alpha/pi)(4),
      which includes the mass-dependent contributions. These results lead to
      a(e)(theory)=1,159,652,181.78(77)*10(-12). The improved value of the fine
      structure constant alpha(-1)=137.035999173 (35) [0.25 ppb] is also derived from
      the theory and measurement of a(e).

PMID- 23005615
TI  - Search for the standard model Higgs boson decaying to a bb pair in events with
      one charged lepton and large missing transverse energy using the full CDF data
      set.
AB  - We present a search for the standard model Higgs boson produced in association
      with a W boson in sqrt[s]=1.96  TeV pp collision data collected with the CDF II
      detector at the Tevatron corresponding to an integrated luminosity of 9.45  fb(
      1). In events consistent with the decay of the Higgs boson to a bottom-quark pair
      and the W boson to an electron or muon and a neutrino, we set 95% credibility
      level upper limits on the WH production cross section times the H->bb branching
      ratio as a function of Higgs boson mass. At a Higgs boson mass of 125  GeV/c(2),
      we observe (expect) a limit of 4.9 (2.8) times the standard model value.

PMID- 23005620
TI  - Measurement of exclusive pi(0) electroproduction structure functions and their
      relationship to transverse generalized parton distributions.
AB  - Exclusive pi(0) electroproduction at a beam energy of 5.75 GeV has been measured
      with the Jefferson Lab CLAS spectrometer. Differential cross sections were
      measured at more than 1800 kinematic values in Q(2), x(B), t, and phi(pi), in the
      Q(2) range from 1.0 to 4.6  GeV(2), -t up to 2  GeV(2), and x(B) from 0.1 to
      0.58. Structure functions sigma(T)+epsilonsigma(L), sigma(TT), and sigma(LT) were
      extracted as functions of t for each of 17 combinations of Q(2) and x(B). The
      data were compared directly with two handbag-based calculations including both
      longitudinal and transversity generalized parton distributions (GPDs). Inclusion
      of only longitudinal GPDs very strongly underestimates sigma(T)+epsilonsigma(L)
      and fails to account for sigma(TT) and sigma(LT), while inclusion of transversity
      GPDs brings the calculations into substantially better agreement with the data.
      There is very strong sensitivity to the relative contributions of nucleon
      helicity-flip and helicity nonflip processes. The results confirm that exclusive
      pi(0) electroproduction offers direct experimental access to the transversity
      GPDs.

PMID- 23005623
TI  - Mechanisms of two-color laser-induced field-free molecular orientation.
AB  - Two mechanisms of two-color (omega+2omega) laser-induced field-free molecular
      orientation, based on the hyperpolarizability and ionization depletion, are
      explored and compared. The CO molecule is used as a computational example. While
      the hyperpolarizability mechanism generates small amounts of orientation at
      intensities below the ionization threshold, ionization depletion quickly becomes
      the dominant mechanism as soon as ionizing intensities are reached. Only the
      ionization mechanism leads to substantial orientation (e.g., on the order of
      <costheta> ?0.1). For intensities typical of laser-induced molecular alignment
      and orientation experiments, the two mechanisms lead to robust, characteristic
      timings of the field-free orientation wave-packet revivals relative to the
      alignment revivals and the revival time. The revival timings can be used to
      detect the active orientation mechanism experimentally.

PMID- 23005616
TI  - Search for the standard model Higgs boson decaying to a bb pair in events with no
      charged leptons and large missing transverse energy using the full CDF data set.
AB  - We report on a search for the standard model Higgs boson produced in association
      with a vector boson in the full data set of proton-antiproton collisions at
      sqrt[s]=1.96  TeV recorded by the CDF II detector at the Tevatron, corresponding
      to an integrated luminosity of 9.45  fb(-1). We consider events having no
      identified charged lepton, a transverse energy imbalance, and two or three jets,
      of which at least one is consistent with originating from the decay of a b quark.
      We place 95% credibility level upper limits on the production cross section times
      standard model branching fraction for several mass hypotheses between 90 and 150 
      GeV/c(2). For a Higgs boson mass of 125  GeV/c(2), the observed (expected) limit
      is 6.7 (3.6) times the standard model prediction.

PMID- 23005622
TI  - New half-lives of r-process Zn and Ga isotopes measured with electromagnetic
      separation.
AB  - The beta decays of neutron-rich nuclei near the doubly magic (78)Ni were studied
      at the Holifield Radioactive Ion Beam Facility using an electromagnetic isobar
      separator. The half-lives of (82)Zn (228+/-10  ms), (83)Zn (117+/-20  ms), and
      (85)Ga (93+/-7  ms) were determined for the first time. These half-lives were
      found to be very different from the predictions of the global model used in
      astrophysical simulations. A new calculation was developed using the density
      functional model, which properly reproduced the new experimental values. The
      robustness of the new model in the (78)Ni region allowed us to extrapolate data
      for more neutron-rich isotopes. The revised analysis of the rapid neutron capture
      process in low entropy environments with our new set of measured and calculated
      half-lives shows a significant redistribution of predicted isobaric abundances
      strengthening the yield of A>140 nuclei.

PMID- 23005624
TI  - Comparisons of positron and electron binding to molecules.
AB  - Positron binding to molecules is compared to the analogous electron-molecule
      bound states. For both, the bound lepton density is diffuse and remains outside
      the valence shell. Positron binding energies are found to be one to two orders of
      magnitude larger than those of the negative ions due to two effects: the
      orientation of the molecular dipole moment allows the positron to approach it
      more closely and, for positrons, lepton correlations (e.g., via dipole
      polarizability) contribute more strongly.

PMID- 23005625
TI  - Ion-lithium collision dynamics studied with a laser-cooled in-ring target.
AB  - We present a novel experimental tool allowing for kinematically complete studies
      of break-up processes of laser-cooled atoms. This apparatus, the 'MOTReMi,' is a
      combination of a magneto-optical trap (MOT) and a reaction microscope (ReMi).
      Operated in an ion-storage ring, the new setup enables us to study the dynamics
      in swift ion-atom collisions on an unprecedented level of precision and detail.
      In the inaugural experiment on collisions with 1.5  MeV/amu O(8+)-Li the pure
      ionization of the valence electron as well as the ionization-excitation of the
      lithium target was investigated.

PMID- 23005626
TI  - Measurement of photon statistics with live photoreceptor cells.
AB  - We analyzed the electrophysiological response of an isolated rod photoreceptor of
      Xenopus laevis under stimulation by coherent and pseudothermal light sources.
      Using the suction-electrode technique for single cell recordings and a fiber
      optics setup for light delivery allowed measurements of the major statistical
      characteristics of the rod response. The results indicate differences in average
      responses of rod cells to coherent and pseudothermal light of the same intensity
      and also differences in signal-to-noise ratios and second-order intensity
      correlation functions. These findings should be relevant for interdisciplinary
      studies seeking applications of quantum optics in biology.

PMID- 23005627
TI  - Observation of orbital angular momentum sidebands due to optical reflection.
AB  - We investigate how the orbital angular momentum of a paraxial light beam is
      affected upon reflection at a planar interface. Theoretically, the unavoidable
      angular spread of the beam leads to orbital angular momentum sidebands, which are
      found to be already significant for a modest beam spread (0.05). In analogy to
      the polarization Fresnel coefficients, we develop an analytical theory based upon
      spatial Fresnel coefficients; this allows a straightforward prediction of the
      strength of the sidebands. We confirm this by experiment and numerical
      simulation.

PMID- 23005629
TI  - Plasma-induced asymmetric self-phase modulation and modulational instability in
      gas-filled hollow-core photonic crystal fibers.
AB  - We study theoretically the propagation of relatively long pulses with ionizing
      intensities in a hollow-core photonic crystal fiber filled with a Raman-inactive
      noble gas. Because of photoionization, an extremely asymmetric self-phase
      modulation and a new kind of "universal" plasma-induced modulational instability
      appear in both normal and anomalous dispersion regions. We also show that it is
      possible to spontaneously generate a plasma-induced continuum of blueshifting
      solitons, opening up new possibilities for pushing supercontinuum generation
      towards shorter and shorter wavelengths.

PMID- 23005628
TI  - Oriented rotational wave-packet dynamics studies via high harmonic generation.
AB  - We produce oriented rotational wave packets in CO and measure their
      characteristics via high harmonic generation. The wave packet is created using an
      intense, femtosecond laser pulse and its second harmonic. A delayed 800 nm pulse
      probes the wave packet, generating even-order high harmonics that arise from the
      broken symmetry induced by the orientation dynamics. The even-order harmonic
      radiation that we measure appears on a zero background, enabling us to accurately
      follow the temporal evolution of the wave packet. Our measurements reveal that,
      for the conditions optimum for harmonic generation, the orientation is produced
      by preferential ionization which depletes the sample of molecules of one
      orientation.

PMID- 23005630
TI  - Nanocavity linewidth narrowing and group delay enhancement by slow light
      propagation and nonlinear effects.
AB  - Slow light induced by coherent population oscillations and cavity dispersive
      nonlinear response are combined achieving 2 orders of magnitude enhancement of
      the group delay and an equivalent decreasing of the spectral linewidth of a L3
      two-dimensional photonic crystal nanocavity.

PMID- 23005631
TI  - High field optical nonlinearity and the Kramers-Kronig relations.
AB  - The nonlinear optical response to high fields is absolutely measured for the
      noble gas atoms He, Ne, Ar, Kr, and Xe. We find that the response is quadratic in
      the laser field magnitude up to the ionization threshold of each gas. Its size
      and quadratic dependence are well predicted by a Kramers-Kronig analysis
      employing known ionization probabilities, and the results are consistent with
      calculations using the time-dependent Schrodinger equation.

PMID- 23005632
TI  - Observation and optical tailoring of photonic lattice filaments.
AB  - We demonstrate, for the first time, that photonic lattices support a new type of
      laser filaments, called lattice filaments (LF). The LF attributes (length, width,
      and intensity) can be tailored by both varying the photonic lattice properties
      and also dynamically through the interaction between filaments. This opens the
      way for extensive all-optical control of the nonlinear propagation of intense
      ultrafast wave packets. Our approach is generic and applicable to all transparent
      media, with potential strong impact on various photonic applications.

PMID- 23005633
TI  - Geometric mechanics of curved crease origami.
AB  - Folding a sheet of paper along a curve can lead to structures seen in decorative
      art and utilitarian packing boxes. Here we present a theory for the simplest such
      structure: an annular circular strip that is folded along a central circular
      curve to form a three-dimensional buckled structure driven by geometrical
      frustration. We quantify this shape in terms of the radius of the circle, the
      dihedral angle of the fold, and the mechanical properties of the sheet of paper
      and the fold itself. When the sheet is isometrically deformed everywhere except
      along the fold itself, stiff folds result in creases with constant curvature and
      oscillatory torsion. However, relatively softer folds inherit the broken symmetry
      of the buckled shape with oscillatory curvature and torsion. Our asymptotic
      analysis of the isometrically deformed state is corroborated by numerical
      simulations that allow us to generalize our analysis to study structures with
      multiple curved creases.

PMID- 23005634
TI  - Nonlinear geometric effects in mechanical bistable morphing structures.
AB  - Bistable structures associated with nonlinear deformation behavior, exemplified
      by the Venus flytrap and slap bracelet, can switch between different functional
      shapes upon actuation. Despite numerous efforts in modeling such large
      deformation behavior of shells, the roles of mechanical and nonlinear geometric
      effects on bistability remain elusive. We demonstrate, through both theoretical
      analysis and tabletop experiments, that two dimensionless parameters control
      bistability. Our work classifies the conditions for bistability, and extends the
      large deformation theory of plates and shells.

PMID- 23005635
TI  - Logarithmic temperature profiles in turbulent Rayleigh-Benard convection.
AB  - We report results for the temperature profiles of turbulent Rayleigh-Benard
      convection (RBC) in the interior of a cylindrical sample of aspect ratio
      Gamma=D/L=0.50 (D and L are the diameter and height, respectively). Both in the
      classical and in the ultimate state of RBC we find that the temperature varies as
      A*ln(z/L)+B, where z is the distance from the bottom or top plate. In the
      classical state, the coefficient A decreases in the radial direction as the
      distance from the side wall increases. For the ultimate state, the radial
      dependence of A has not yet been determined. These findings are based on
      experimental measurements over the Rayleigh-number range 4*10(12)?Ra?10(15) for a
      Prandtl number Pr?0.8 and on direct numerical simulation at Ra=2*10(12),
      2*10(11), and 2*10(10), all for Pr=0.7.

PMID- 23005636
TI  - Oscillon dynamics and rogue wave generation in Faraday surface ripples.
AB  - We report new experimental results which suggest that the generation of extreme
      wave events in the Faraday surface ripples is related to the increase in the
      horizontal mobility of oscillating solitons (oscillons). The analysis of the
      oscillon trajectories in a horizontal plane shows that at higher vertical
      acceleration, oscillons move chaotically, merge and form enclosed areas on the
      water surface. The probability of the formation of such craters, which precede
      large wave events, increases with the increase in horizontal mobility.

PMID- 23005637
TI  - Magnetic field generation by the Rayleigh-Taylor instability in laser-driven
      planar plastic targets.
AB  - Magnetic fields generated by the Rayleigh-Taylor instability were measured in
      laser-accelerated planar foils using ultrafast proton radiography. Thin plastic
      foils were irradiated with ~4-kJ, 2.5-ns laser pulses focused to an intensity of
      ~10(14)  W/cm(2) on the OMEGA EP Laser System. Target modulations were seeded by
      laser nonuniformities and amplified during target acceleration by the Rayleigh
      Taylor instability. The experimental data show the hydrodynamic evolution of the
      target and MG-level magnetic fields generated in the broken foil. The
      experimental data are in good agreement with predictions from 2-D
      magnetohydrodynamic simulations.

PMID- 23005638
TI  - Electron emission at locked phases from the laser-driven surface plasma wave.
AB  - By irradiating a flat Al target with femtosecond laser pulses at moderate
      intensities of ~10(17)  W/cm(2), we obtained stable collimated quasimonoenergetic
      electrons in the specular direction but deviated somewhat toward the target
      normal. An associated local minimum located on the other side of the specular
      direction seems to indicate that the peak actually results from the deflection of
      the collimated electrons from their initial ejection direction. We have proposed
      a two-step model in which some laser-accelerated electrons are able to leave the
      plasma in a narrow phase-locked window of the moving wave interference pattern,
      and are then steered toward the target normal by the ponderomotive force of the
      interference field. The periodic repetition of the electron emission leads to a
      pulse train of collimated quasimonoenergetic electrons with subcycle duration.

PMID- 23005639
TI  - Fast-particle-driven Alfvenic modes in a reversed field pinch.
AB  - Alfvenic modes are observed due to neutral beam injection for the first time in a
      reversed field pinch plasma. Modeling of the beam deposition and slowing down
      shows that the velocity and radial localization are high. This allows instability
      drive from inverse Landau damping of a bump-on-tail in the parallel distribution
      function or from free energy in the fast ion density gradient. Mode switching
      from a lower frequency toroidal mode number n=5 mode that scales with beam
      injection velocity to a higher frequency n=4 mode with Alfvenic scaling is
      observed.

PMID- 23005640
TI  - Demonstration of anisotropic fluid closure capturing the kinetic structure of
      magnetic reconnection.
AB  - Collisionless magnetic reconnection in high-temperature plasmas has been widely
      studied through fluid-based models. Here, we present results of fluid simulation
      implementing new equations of state for guide-field reconnection. The new fluid
      closure accurately accounts for the anisotropic electron pressure that builds in
      the reconnection region due to electric and magnetic trapping of electrons. In
      contrast to previous fluid models, our fluid simulation reproduces the detailed
      reconnection region as observed in fully kinetic simulations. We hereby
      demonstrate that the new fluid closure self-consistently captures all the physics
      relevant to the structure of the reconnection region, providing a gateway to a
      renewed and deeper theoretical understanding of reconnection in weakly
      collisional regimes.

PMID- 23005641
TI  - Collective dipole oscillations of a spin-orbit coupled Bose-Einstein condensate.
AB  - In this Letter, we present an experimental study of the collective dipole
      oscillation of a spin-orbit coupled Bose-Einstein condensate in a harmonic trap.
      The dynamics of the center-of-mass dipole oscillation is studied in a broad
      parameter region as a function of spin-orbit coupling parameters as well as the
      oscillation amplitude. The anharmonic properties beyond the effective-mass
      approximation are revealed, such as the amplitude-dependent frequency and finite
      oscillation frequency at a place with a divergent effective mass. These
      anharmonic behaviors agree quantitatively with variational wave-function
      calculations. Moreover, we experimentally demonstrate a unique feature of the
      spin-orbit coupled system predicted by a sum-rule approach, stating that spin
      polarization susceptibility--a static physical quantity--can be measured via the
      dynamics of dipole oscillation. The divergence of polarization susceptibility is
      observed at the quantum phase transition that separates the magnetic nonzero
      momentum condensate from the nonmagnetic zero-momentum phase. The good agreement
      between the experimental and theoretical results provides a benchmark for
      recently developed theoretical approaches.

PMID- 23005642
TI  - Creation of ultracold Sr(2) molecules in the electronic ground state.
AB  - We report on the creation of ultracold (84)Sr(2) molecules in the electronic
      ground state. The molecules are formed from atom pairs on sites of an optical
      lattice using stimulated Raman adiabatic passage (STIRAP). We achieve a transfer
      efficiency of 30% and obtain 4*10(4) molecules with full control over the
      external and internal quantum state. STIRAP is performed near the narrow (1)S(0)
      (3)P(1) intercombination transition, using a vibrational level of the 1(0(u)(+))
      potential as an intermediate state. In preparation of our molecule association
      scheme, we have determined the binding energies of the last vibrational levels of
      the 1(0(u)(+)), 1(1(u)) excited-state and the X (1)Sigma(g)(+) ground-state
      potentials. Our work overcomes the previous limitation of STIRAP schemes to
      systems with magnetic Feshbach resonances, thereby establishing a route that is
      applicable to many systems beyond alkali-metal dimers.

PMID- 23005643
TI  - Optical production of stable ultracold (88)Sr(2) molecules.
AB  - We have produced large samples of stable ultracold (88)Sr(2) molecules in the
      electronic ground state in an optical lattice. The fast, all-optical method of
      molecule creation involves a near-intercombination-line photoassociation pulse
      followed by spontaneous emission with a near-unity Franck-Condon factor. The
      detection uses excitation to a weakly bound electronically excited vibrational
      level corresponding to a very large dimer and yields a high-Q molecular vibronic
      resonance. This is the first of two steps needed to create deeply bound (88)Sr(2)
      for frequency metrology and ultracold chemistry.

PMID- 23005644
TI  - Quench dynamics of the interacting Bose gas in one dimension.
AB  - We obtain an exact expression for the time evolution of the interacting Bose gas
      following a quench from a generic initial state using the Yudson representation
      for integrable systems. We study the time evolution of the density and noise
      correlation for a small number of bosons and their asymptotic behavior for any
      number. We show that for any value of the coupling, as long as it is repulsive,
      the system asymptotes towards a strongly repulsive gas, while for any value of an
      attractive coupling the long time behavior is dominated by the maximal bound
      state. This occurs independently of the initial state and can be viewed as an
      emerging "dynamic universality."

PMID- 23005645
TI  - Nucleation and growth in shock-induced phase transitions and how they determine
      wave profile features.
AB  - Wave profile measurement and interpretation play a central role in shock physics
      research. We propose an approach to revealing the direct link between the wave
      profile and nucleation and growth process in shock-induced phase transition.
      Through phase field simulations, we show for the first time that it is possible
      to explain experimentally measured wave profiles directly from the viewpoint of
      nucleation and growth, and constrain from such profiles real nucleation and
      growth scenarios that are otherwise impossible to study.

PMID- 23005646
TI  - How do glassy domains grow?
AB  - We construct equations for the growth kinetics of structural glass within mode
      coupling theory, through a nonstationary variant of the three-density correlator
      defined by G. Biroli et al. [Phys. Rev. Lett. 97, 195701 (2006)]. We solve a
      schematic form of the resulting equations to obtain the coarsening of the three
      point correlator chi(3)(t,t(w)) as a function of waiting time t(w). For a quench
      into the glass, we find that chi(3) attains a peak value ~t(w)(0.5) at t
      t(w)~t(w)(0.8), providing a theoretical basis for the numerical observations of
      Parisi [J. Phys. Chem. B 103, 4128 (1999)] and Kob and Barrat [Phys. Rev. Lett.
      78, 4581 (1997)]. The aging is not "simple": the t(w) dependence cannot be
      attributed to an evolving effective temperature.

PMID- 23005647
TI  - Assisted finite-rate adiabatic passage across a quantum critical point: exact
      solution for the quantum Ising model.
AB  - The dynamics of a quantum phase transition is inextricably woven with the
      formation of excitations, as a result of critical slowing down in the
      neighborhood of the critical point. We design a transitionless quantum driving
      through a quantum critical point, allowing one to access the ground state of the
      broken-symmetry phase by a finite-rate quench of the control parameter. The
      method is illustrated in the one-dimensional quantum Ising model in a transverse
      field. Driving through the critical point is assisted by an auxiliary
      Hamiltonian, for which the interplay between the range of the interaction and the
      modes where excitations are suppressed is elucidated.

PMID- 23005648
TI  - Superfunctionalities in nanodispersive precipitation-hardened alloys.
AB  - Although nanodispersive precipitation-hardened alloys have been intensively
      studied over decades as important structural materials, the possibility that
      these alloys may have superfunctional properties has been completely overlooked.
      As shown in this Letter, they may have giant low-hysteretic strain responses to
      external stimuli if the nanosized single-domain precipitates can switch their
      orientation variants under applied fields. We demonstrate that the misfit
      generated coherency stress can significantly reduce the variant switching
      barriers and may drastically decrease or even eliminate the hysteresis of the
      strain super responses to external stress and/or magnetic fields. These alloys
      can thus be functionalized as shape memory, superelastic, and/or
      supermagnetostrictive materials. The conditions of such functionalization are
      established by the interpretation-transparent analytical calculations, and
      confirmed by computer prototyping. In particular, the obtained results pave the
      way for the engineering of rare-earth free alloys with excellent
      magnetomechanical and good mechanical properties.

PMID- 23005649
TI  - Slow processes in supercooled o-terphenyl: relaxation and decoupling.
AB  - We mapped the relaxation times of inter- and intramolecular correlations in o
      terphenyl by a quasielastic scattering method using nuclear resonant scattering
      of synchrotron radiation. From the obtained map, we found that the slow beta
      process is decoupled from the alpha process at 278 K, and this temperature is
      clearly below the previous decoupling temperature of 290 K, at which the alpha
      relaxation dynamics changes. Then, it was also concluded that sufficient
      solidlike condition achieved by further cooling from 290 K is required to
      decouple the slow beta process from the alpha process and, due to the difference
      of the length scales between the alpha and the slow beta processes, these two
      averaged relaxation times <tau> are concluded not to cross as an extrapolation
      assumed so far. Furthermore, evidence of the restricted dynamics of the slow beta
      process could be obtained as an anomalous momentum transfer (q) dependence of
      <tau>(<tau> ?q(-2.9)) at 265 K, observed at q values of 18-48  nm(-1).

PMID- 23005650
TI  - Evaporation of droplets on superhydrophobic surfaces: surface roughness and small
      droplet size effects.
AB  - Evaporation of a sessile droplet is a complex, nonequilibrium phenomenon.
      Although evaporating droplets upon superhydrophobic surfaces have been known to
      exhibit distinctive evaporation modes such as a constant contact line (CCL), a
      constant contact angle (CCA), or both, our fundamental understanding of the
      effects of surface roughness on the wetting transition remains elusive. We show
      that the onset time for the CCL-CCA transition and the critical base size at the
      Cassie-Wenzel transition exhibit remarkable dependence on the surface roughness.
      Through global interfacial energy analysis we reveal that, when the size of the
      evaporating droplet becomes comparable to the surface roughness, the line tension
      at the triple line becomes important in the prediction of the critical base size.
      Last, we show that both the CCL evaporation mode and the Cassie-Wenzel transition
      can be effectively inhibited by engineering a surface with hierarchical
      roughness.

PMID- 23005651
TI  - Spin friction observed on the atomic scale.
AB  - With the advent of scanning probe microscopy techniques that involve a tip and a
      sample in relative motion in the contact or noncontact regime, the microscopic
      aspects of friction have become a major branch of research called nanotribology.
      A significant number of recent studies in this field have concentrated on the
      distinction between electronic and phononic contributions to friction. Here, we
      are using the combination of spin-polarized scanning tunneling microscopy and
      single-atom manipulation in order to move individual magnetic atoms over a
      magnetic template. By monitoring the spin-resolved manipulation traces and
      comparing them with results of Monte Carlo simulations, we are able to reveal the
      characteristic friction force variations resulting from the occurrence of spin
      friction on the atomic scale.

PMID- 23005652
TI  - Reentrant wetting of network fluids.
AB  - We use a simple mesoscopic Landau-Safran theory of network fluids to show that a
      reentrant phase diagram, in the "empty liquid" regime, leads to nonmonotonic
      surface tension and reentrant wetting, as previously reported for binary
      mixtures. One of the wetting transitions is of the usual kind, but the low
      temperature transition may allow the display of the full range of fluctuation
      regimes predicted by renormalization group theory.

PMID- 23005653
TI  - Quantum oscillations and high carrier mobility in the delafossite PdCoO(2).
AB  - We present de Haas-van Alphen and resistivity data on single crystals of the
      delafossite PdCoO(2). At 295 K we measure an in-plane resistivity of 2.6  MUOmega
      cm, making PdCoO(2) the most conductive oxide known. The low-temperature in-plane
      resistivity has an activated rather than the usual T(5) temperature dependence,
      suggesting a gapping of effective scattering that is consistent with phonon drag.
      Below 10 K, the transport mean free path is ~20  MUm, approximately 10(5) lattice
      spacings and an astoundingly high value for flux-grown crystals. We discuss the
      origin of these properties in light of our data.

PMID- 23005654
TI  - Quasiparticle entropy in the high-field superconducting phase of CeCoIn(5).
AB  - The heavy-fermion superconductor CeCoIn(5) displays an additional transition
      within its superconducting (SC) state, whose nature is characterized by high
      precision studies of the isothermal field dependence of the entropy, derived from
      combined specific heat and magnetocaloric effect measurements at temperatures
      T>=100  mK and fields H<=12  T aligned along different directions. For any of
      these conditions, we do not observe an additional entropy contribution upon
      tuning at constant temperature by magnetic field from the homogeneous SC into the
      presumed Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) SC state. By contrast, for
      H?[100] a reduction of entropy was found that quantitatively agrees with the
      expectation for spin-density-wave order without FFLO superconductivity. Our data
      exclude the formation of a FFLO state in CeCoIn(5) for out-of-plane field
      directions, where no spin-density-wave order exists.

PMID- 23005655
TI  - Disentanglement of surface and bulk Rashba spin splittings in noncentrosymmetric
      BiTeI.
AB  - BiTeI has a layered and noncentrosymmetric structure where strong spin-orbit
      interaction leads to a giant Rashba spin splitting in the bulk bands. We present
      direct measurements of the bulk band structure obtained with soft x-ray angle
      resolved photoemission (ARPES), revealing the three-dimensional Fermi surface.
      The observed spindle torus shape bears the potential for a topological transition
      in the bulk by hole doping. Moreover, the bulk electronic structure is clearly
      disentangled from the two-dimensional surface electronic structure by means of
      high-resolution and spin-resolved ARPES measurements in the ultraviolet regime.
      All findings are supported by ab initio calculations.

PMID- 23005656
TI  - Topological equivalence between the Fibonacci quasicrystal and the Harper model.
AB  - One-dimensional quasiperiodic systems, such as the Harper model and the Fibonacci
      quasicrystal, have long been the focus of extensive theoretical and experimental
      research. Recently, the Harper model was found to be topologically nontrivial.
      Here, we derive a general model that embodies a continuous deformation between
      these seemingly unrelated models. We show that this deformation does not close
      any bulk gaps, and thus prove that these models are in fact topologically
      equivalent. Remarkably, they are equivalent regardless of whether the
      quasiperiodicity appears as an on-site or hopping modulation. This proves that
      these different models share the same boundary phenomena and explains past
      measurements. We generalize this equivalence to any Fibonacci-like quasicrystal,
      i.e., a cut and project in any irrational angle.

PMID- 23005657
TI  - Bound states in the continuum realized in the one-dimensional two-particle
      Hubbard model with an impurity.
AB  - We report a bound state of the one-dimensional two-particle (bosonic or
      fermionic) Hubbard model with an impurity potential. This state has the Bethe
      ansatz form, although the model is nonintegrable. Moreover, for a wide region in
      parameter space, its energy is located in the continuum band. A remarkable
      advantage of this state with respect to similar states in other systems is the
      simple analytical form of the wave function and eigenvalue. This state can be
      tuned in and out of the continuum continuously.

PMID- 23005658
TI  - Prediction of weak topological insulators in layered semiconductors.
AB  - We report the discovery of weak topological insulators by ab initio calculations
      in a honeycomb lattice. We propose a structure with an odd number of layers in
      the primitive unit cell as a prerequisite for forming weak topological
      insulators. Here, the single-layered KHgSb is the most suitable candidate for its
      large bulk energy gap of 0.24 eV. Its side surface hosts metallic surface states,
      forming two anisotropic Dirac cones. Although the stacking of even-layered
      structures leads to trivial insulators, the structures can host a quantum spin
      Hall layer with a large bulk gap, if an additional single layer exists as a
      stacking fault in the crystal. The reported honeycomb compounds can serve as
      prototypes to aid in the finding of new weak topological insulators in layered
      small-gap semiconductors.

PMID- 23005659
TI  - Effect of electron-phonon interaction range for a half-filled band in one
      dimension.
AB  - We demonstrate that fermion-boson models with nonlocal interactions can be
      simulated at finite band filling with the continuous-time quantum Monte Carlo
      method. We apply this method to explore the influence of the electron-phonon
      interaction range for a half-filled band in one dimension, covering the full
      range from the Holstein to the Frohlich regime. The phase diagram contains
      metallic, Peierls, and phase-separated regions. Nonlocal interactions suppress
      the Peierls instability, and thereby lead to almost degenerate power-law
      exponents for charge and pairing correlations.

PMID- 23005621
TI  - Production of muons from heavy flavor decays at forward rapidity in pp and Pb-Pb
      collisions at sqrt[s(NN)]=2.76  TeV.
AB  - The ALICE Collaboration has measured the inclusive production of muons from heavy
      flavor decays at forward rapidity, 2.5<y<4, in pp and Pb-Pb collisions at
      sqrt[s(NN)]=2.76  TeV. The p(t)-differential inclusive cross section of muons
      from heavy-flavor decays in pp collisions is compared to perturbative QCD
      calculations. The nuclear modification factor is studied as a function of p(t)
      and collision centrality. A weak suppression is measured in peripheral
      collisions. In the most central collisions, a suppression of a factor of about 3
      4 is observed in 6<p(t)<10  GeV/c. The suppression shows no significant p(t)
      dependence.

PMID- 23005660
TI  - First principles calculation of the shift current photovoltaic effect in
      ferroelectrics.
AB  - We calculate the bulk photovoltaic response of the ferroelectrics BaTiO(3) and
      PbTiO(3) from first principles by applying the "shift current" theory to the
      electronic structure from density functional theory. The first principles results
      for BaTiO(3) reproduce experimental photocurrent direction and magnitude as a
      function of light frequency, as well as the dependence of current on light
      polarization, demonstrating that shift current is the dominant mechanism of the
      bulk photovoltaic effect in BaTiO(3). Additionally, we analyze the relationship
      between response and material properties in detail. Photocurrent does not depend
      simply or strongly on the magnitude of material polarization, as has been
      previously assumed; instead, electronic states with delocalized, covalent bonding
      that is highly asymmetric along the current direction are required for strong
      shift current enhancements. The complexity of the response dependence on both
      external and material parameters suggests applications not only in solar energy
      conversion, but in photocatalysis and sensor and switch type devices as well.

PMID- 23005661
TI  - Quantitative analysis of valence photoemission spectra and quasiparticle
      excitations at chromophore-semiconductor interfaces.
AB  - Investigating quasiparticle excitations of molecules on surfaces through
      photoemission spectroscopy forms a major part of nanotechnology research.
      Resolving spectral features at these interfaces requires a comprehensive theory
      of electron removal and addition processes in molecules and solids which captures
      the complex interplay of image charges, thermal effects, and configurational
      disorder. Here, we develop such a theory and calculate the quasiparticle energy
      level alignment and the valence photoemission spectrum for the prototype
      biomimetic solar cell interface between anatase TiO(2) and the N3 chromophore. By
      directly matching our calculated photoemission spectrum to experimental data, we
      clarify the atomistic origin of the chromophore peak at low binding energy. This
      case study sets a new standard in the interpretation of photoemission
      spectroscopy at complex chromophore-semiconductor interfaces.

PMID- 23005662
TI  - Renormalization of the graphene dispersion velocity determined from scanning
      tunneling spectroscopy.
AB  - In graphene, as in most metals, electron-electron interactions renormalize the
      properties of electrons but leave them behaving like noninteracting
      quasiparticles. Many measurements probe the renormalized properties of electrons
      right at the Fermi energy. Uniquely for graphene, the accessibility of the
      electrons at the surface offers the opportunity to use scanned probe techniques
      to examine the effect of interactions at energies away from the Fermi energy,
      over a broad range of densities, and on a local scale. Using scanning tunneling
      spectroscopy, we show that electron interactions leave the graphene energy
      dispersion linear as a function of excitation energy for energies within +/-200 
      meV of the Fermi energy. However, the measured dispersion velocity depends on
      density and increases strongly as the density approaches zero near the charge
      neutrality point, revealing a squeezing of the Dirac cone due to interactions.

PMID- 23005663
TI  - Stabilizing topological phases in graphene via random adsorption.
AB  - We study the possibility of realizing topological phases in graphene with
      randomly distributed adsorbates. When graphene is subjected to periodically
      distributed adatoms, the enhanced spin-orbit couplings can result in various
      topological phases. However, at certain adatom coverages, the intervalley
      scattering renders the system a trivial insulator. By employing a finite-size
      scaling approach and Landauer-Buttiker formula, we show that the randomization of
      adatom distribution greatly weakens the intervalley scattering, but plays a
      negligible role in spin-orbit couplings. Consequently, such a randomization turns
      graphene from a trivial insulator into a topological state.

PMID- 23005664
TI  - Thickness-independent transport channels in topological insulator Bi(2)Se(3) thin
      films.
AB  - With high quality topological insulator Bi(2)Se(3) thin films, we report
      thickness-independent transport properties over wide thickness ranges.
      Conductance remained nominally constant as the sample thickness changed from 256
      to ~8  QL (where QL refers to quintuple layer, 1  QL~1  nm). Two surface channels
      of very different behaviors were identified. The sheet carrier density of one
      channel remained constant at ~3.0*10(13)  cm(-2) down to 2 QL, while the other,
      which exhibited quantum oscillations, remained constant at ~8*10(12)  cm(-2) only
      down to ~8  QL. The weak antilocalization parameters also exhibited similar
      thickness independence. These two channels are most consistent with the
      topological surface states and the surface accumulation layers, respectively.

PMID- 23005665
TI  - Robust nodal structure of Landau level wave functions revealed by Fourier
      transform scanning tunneling spectroscopy.
AB  - Scanning tunneling spectroscopy is used to study the real-space local density of
      states of a two-dimensional electron system in a magnetic field, in particular
      within higher Landau levels. By Fourier transforming the local density of states,
      we find a set of n radial minima at fixed momenta for the nth Landau levels. The
      momenta of the minima depend only on the inverse magnetic length. By comparison
      with analytical theory and numerical simulations, we attribute the minima to the
      nodes of the quantum cyclotron orbits, which decouple in a Fourier representation
      from the random guiding center motion due to disorder. Adequate Fourier filtering
      reveals the nodal structure in real space in some areas of the sample with
      relatively smooth potential disorder.

PMID- 23005666
TI  - Possibility of valence-fluctuatsion-mediated superconductivity in Cd-doped
      CeIrIn(5) probed by In NQR.
AB  - We report on a pressure-induced evolution of exotic superconductivity and spin
      correlations in CeIr(In(1-x)Cd(x))(5) by means of in-nuclear-quadrupole-resonance
      (NQR) studies. Measurements of an NQR spectrum and nuclear-spin-lattice
      relaxation rate 1/T(1) have revealed that antiferromagnetism induced by Cd doping
      emerges locally around Cd dopants, but superconductivity is suddenly induced at
      T(c)=0.7 and 0.9 K at 2.34 and 2.75 GPa, respectively. The unique superconducting
      characteristics with a large fraction of the residual density of state at the
      Fermi level which increases with T(c) differ from those for anisotropic
      superconductivity mediated by antiferromagnetic correlations. By incorporating
      the pressure dependence of the NQR frequency pointing to the valence change of
      Ce, we suggest that unconventional superconductivity in the CeIr(In(1-x)Cd(x))(5)
      system may be mediated by valence fluctuations.

PMID- 23005667
TI  - Fe spin reorientation across the metamagnetic transition in strained FeRh thin
      films.
AB  - A spin reorientation accompanying the temperature-induced antiferromagnetic (AFM)
      to ferromagnetic (FM) phase transition is reported in strained epitaxial FeRh
      thin films. (57)Fe conversion electron Mossbauer spectrometry showed that the Fe
      moments have different orientations in FeRh grown on thick single-crystalline MgO
      and in FeRh grown on ion-beam-assist-deposited (IBAD) MgO. It was also observed,
      in both samples, that the Fe moments switch orientations at the AFM to FM phase
      transition. Perpendicular anisotropy was evidenced in the AFM phase of the film
      grown on IBAD MgO and in the FM phase of that grown on regular MgO. Density
      functional theory calculations enabled this spin-reorientation transition to be
      accurately reproduced for both FeRh films across the AFM-FM phase transition and
      show that these results are due to differences in strain.

PMID- 23005668
TI  - Topological defects and misfit strain in magnetic stripe domains of lateral
      multilayers with perpendicular magnetic anisotropy.
AB  - Stripe domains are studied in perpendicular magnetic anisotropy films
      nanostructured with a periodic thickness modulation that induces the lateral
      modulation of both stripe periods and in-plane magnetization. The resulting
      system is the 2D equivalent of a strained superlattice with properties controlled
      by interfacial misfit strain within the magnetic stripe structure and shape
      anisotropy. This allows us to observe, experimentally for the first time, the
      continuous structural transformation of a grain boundary in this 2D magnetic
      crystal in the whole angular range. The magnetization reversal process can be
      tailored through the effect of misfit strain due to the coupling between
      disclinations in the magnetic stripe pattern and domain walls in the in-plane
      magnetization configuration.

PMID- 23005669
TI  - Singlet ground state of the quantum antiferromagnet Ba(3)CuSb(2)O(9).
AB  - We present local probe results on the honeycomb lattice antiferromagnet
      Ba(3)CuSb(2)O(9). Muon spin relaxation measurements in a zero field down to 20 mK
      show unequivocally that there is a total absence of spin freezing in the ground
      state. Sb NMR measurements allow us to track the intrinsic susceptibility of the
      lattice, which shows a maximum at around 55 K and drops to zero in the low
      temperature limit. The spin-lattice relaxation rate shows two characteristic
      energy scales, including a field-dependent crossover to exponential low
      temperature behavior, implying gapped magnetic excitations.

PMID- 23005670
TI  - Unified drift-diffusion theory for transverse spin currents in spin valves,
      domain walls, and other textured magnets.
AB  - Spins transverse to the magnetization of a ferromagnet only survive over a short
      distance. We develop a drift-diffusion approach that captures the main features
      of transverse spin effects in systems with arbitrary spin textures (e.g.,
      vortices and domain walls) and generalizes the Valet-Fert theory. In addition to
      the standard characteristic lengths (mean free path for majority and minority
      electrons, and spin diffusion length), the theory introduces two length scales,
      the transverse spin coherence length l(?) and the (Larmor) spin precession length
      l(L). We show how l(L) and l(?) can be extracted from ab initio calculations or
      measured with giant magnetoresistance experiments. In long (adiabatic) domain
      walls, we provide an analytic formula that expresses the so-called "nonadiabatic"
      (or fieldlike) torque in terms of these length scales. However, this nonadiabatic
      torque is no longer a simple material parameter but depends on the actual spin
      texture: in thin (<10  nm) domain walls, we observe very significant deviations
      from the adiabatic limit.

PMID- 23005671
TI  - Mechanism of localization of the magnetization reversal in 3 nm wide Co
      nanowires.
AB  - The mechanism of magnetization reversal has been studied in a model system of
      self-assembled cobalt nanowires with a 3 nm diameter. The structure, orientation
      and size of grains within the nanowires could be determined by high resolution
      transmission electron microscopy. The magnetic properties were probed using
      static and dynamic magnetization measurements. Micromagnetic modeling based on
      the structural analysis allows us to correlate the structure and the magnetic
      behavior of the wires, revealing competition between shape anisotropy,
      magnetocrystalline anisotropy and exchange in the localized reversal within Co
      hcp oriented grains. These results provide direct experimental evidence of the
      link between anisotropy fluctuations and reversal localization in nanowires.

PMID- 23005672
TI  - Spin state of negative charge-transfer material SrCoO(3).
AB  - We employ the combination of the density functional theory and the dynamical mean
      field theory to investigate the electronic structure and magnetic properties of
      SrCoO(3), monocrystals of which were prepared recently. Our calculations lead to
      a ferromagnetic metal in agreement with experiment. We find that, contrary to
      some suggestions, the local moment in SrCoO(3) does not arise from intermediate
      spin state, but is a result of coherent superposition of many different atomic
      states. We discuss how the attribution of magnetic response to different atomic
      states in solids with local moments can be quantified.

PMID- 23005673
TI  - Ca(2)Y(2)Cu(5)O(10): the first frustrated quasi-1D ferromagnet close to
      criticality.
AB  - Ca(2)Y(2)Cu(5)O(10) is built up from edge-shared CuO(4) plaquettes forming spin
      chains. From inelastic neutron scattering data we extract an in-chain nearest
      neighbor exchange J(1)~-170  K and the frustrating next-neighbor J(2)~32  K
      interactions, both significantly larger than previous estimates. The ratio
      alpha=|J(2)/J(1)|=0.19+/-0.01 places the system close to the critical point
      alpha(c)=0.25 of the J(1)-J(2) chain but in the 1D ferromagnetic regime. We
      establish that the vicinity to criticality only marginally affects the dispersion
      and coherence of the spin-wave-like magnetic excitations but instead results in a
      dramatic T dependence of high-energy Zhang-Rice singlet excitation intensities.

PMID- 23005674
TI  - Unraveling orbital correlations with magnetic resonant inelastic x-ray
      scattering.
AB  - Although orbital degrees of freedom are a factor of fundamental importance in
      strongly correlated transition-metal compounds, orbital correlations and dynamics
      remain very difficult to access, in particular by neutron scattering. Via a
      direct calculation of scattering amplitudes we show that instead magnetic
      resonant inelastic x-ray scattering (RIXS) does reveal orbital correlations. In
      contrast to neutron scattering, the intensity of the magnetic excitations in RIXS
      depends very sensitively on the symmetry of the orbitals that spins occupy and on
      photon polarizations. We show in detail how this effect allows magnetic RIXS to
      distinguish between alternating orbital-ordered and ferro-orbital (or orbital
      liquid) states.

PMID- 23005675
TI  - Defect-mediated lattice relaxation and domain stability in ferroelectric oxides.
AB  - The effects of the lattice strain induced by neutral oxygen vacancies in
      ferroelectric tetragonal BaTiO(3) and KNbO(3) are investigated using ab initio
      simulations. We propose that an oxygen vacancy can transform from its metastable
      equatorial configuration to the stable axial configuration via either diffusion
      or rotation of the polar axis near the vacancy site by 90 degrees . The latter
      mechanism, predicted to dominate in materials with slow oxygen vacancy diffusion
      and low formation energy of 90 degrees  domain walls, can stimulate the formation
      of domains with their polar axes pinned by the vacancies.

PMID- 23005677
TI  - Nanoparticle effect on the dynamics of polymer chains and their entanglement
      network.
AB  - We explore the dynamics of entangled polymer chains embedded into nanocomposites.
      From primitive path analysis, highly entangled polymer chains are found to be
      significantly disentangled during increment of the volume fraction of spherical
      nonattractive nanoparticles (NPs) from 0 to 42%. A critical volume fraction,
      phi(c)=31%, is found to control the crossover from polymer chain entanglements to
      "NP entanglements." While below phi(c), the polymer chain relaxation accelerates
      upon filling, above phi(c), the situation reverses: polymer dynamics becomes
      geometrically constrained upon adding NPs. Our findings provide a microscopic
      understanding of the dynamics of entangled polymer chains inside their
      composites, and offer an explanation for the unusual rheological properties of
      polymer composites.

PMID- 23005676
TI  - Phase diagram for nanostructuring CaF(2) surfaces by slow highly charged ions.
AB  - The impact of individual slow highly charged ions (HCI) on alkaline earth halide
      and alkali halide surfaces creates nano-scale surface modifications. For
      different materials and impact energies a wide variety of topographic alterations
      have been observed, ranging from regularly shaped pits to nanohillocks. We
      present experimental evidence for the creation of thermodynamically stable defect
      agglomerations initially hidden after irradiation but becoming visible as pits
      upon subsequent etching. A well defined threshold separating regions with and
      without etch-pit formation is found as a function of potential and kinetic
      energies of the projectile. Combining this novel type of surface defects with the
      previously identified hillock formation, a phase diagram for HCI induced surface
      restructuring emerges. The simulation of the energy deposition by the HCI in the
      crystal provides insight into the early stages of the dynamics of the surface
      modification and its dependence on the kinetic and potential energies.

PMID- 23005678
TI  - Stochastic-shielding approximation of Markov chains and its application to
      efficiently simulate random ion-channel gating.
AB  - Markov chains provide realistic models of numerous stochastic processes in
      nature. We demonstrate that in any Markov chain, the change in occupation number
      in state A is correlated to the change in occupation number in state B if and
      only if A and B are directly connected. This implies that if we are only
      interested in state A, fluctuations in B may be replaced with their mean if state
      B is not directly connected to A, which shortens computing time considerably. We
      show the accuracy and efficacy of our approximation theoretically and in
      simulations of stochastic ion-channel gating in neurons.

PMID- 23005679
TI  - General theory of genotype to phenotype mapping: derivation of epigenetic
      landscapes from N-node complex gene regulatory networks.
AB  - We propose a systematic methodology to construct a probabilistic epigenetic
      landscape of cell-fate attainment associated with N-node Boolean genetic
      regulatory networks. The general derivation proposed here is exemplified with an
      Arabidopsis thaliana network underlying floral organ determination grounded on
      qualitative experimental data.

PMID- 23005680
TI  - Kinetic control of nucleosome displacement by ISWI/ACF chromatin remodelers.
AB  - Chromatin structure is dynamically organized by chromatin remodelers, motor
      protein complexes which move and remove nucleosomes. The regulation of remodeler
      action has recently been proposed to underlie a kinetic proofreading scheme which
      combines the recognition of histone-tail states and the ATP-dependent loosening
      of DNA around nucleosomes. Members of the ISWI-family of remodelers additionally
      recognize linker length between nucleosomes. Here, we show that the additional
      proofreading step involving linker length alone is sufficient to promote the
      formation of regular arrays of nucleosomes. ATP-dependent remodeling by
      bidirectional motors is shown to reinforce positioning as compared to statistical
      positioning.

PMID- 23005681
TI  - Collective predation and escape strategies.
AB  - The phenomenon of collective predation is analyzed by using a simple individual
      based model reproducing spatial animal movements. Two groups of self-propelled
      organisms are simulated by using Vicseklike models including steric intragroup
      repulsion. Chase and escape are described by intergroups interactions, attraction
      (for predators) or repulsion (for preys) from nearest particles of the opposite
      group. The quantitative analysis of some relevant quantities (total catch time,
      lifetime distribution, predation rate) allows us to characterize many aspects of
      the predation phenomenon and gives insights into the study of efficient escape
      strategies. The reported findings could be of relevance for many basic and
      applied disciplines, from statistical physics, to ecology, and robotics.

PMID- 23005682
TI  - Measurement of single cell refractive index, dry mass, volume, and density using
      a transillumination microscope.
AB  - Phase contrast microscopy has become ubiquitous in the field of biology,
      particularly in qualitative investigations of cellular morphology. However, the
      use of quantitative phase retrieval methods and their connection to cellular
      refractive index and dry mass density remain under utilized. This is due in part
      to the restriction of phase and cellular mass determination to custom built
      instruments, involved mathematical analysis, and prohibitive sample
      perturbations. We introduce tomographic bright field imaging, an accessible
      optical imaging technique enabling the three dimensional measurement of cellular
      refractive index and dry mass density using a standard transillumination optical
      microscope. The validity of the technique is demonstrated on polystyrene spheres.
      The technique is then applied to the measurement of the refractive index, dry
      mass, volume, and density of red blood cells. This optical technique enables a
      simple and robust means to perform quantitative investigations of engineered and
      biological specimens in three dimensions using standard optical microscopes.

PMID- 23005683
TI  - Negative curvature boundaries as wave emitting sites for the control of
      biological excitable media.
AB  - Understanding the interaction of electric fields with the complex anatomy of
      biological excitable media is key to optimizing control strategies for
      spatiotemporal dynamics in those systems. On the basis of a bidomain description,
      we provide a unified theory for the electric-field-induced depolarization of the
      substrate near curved boundaries of generalized shapes, resulting in the
      localized recruitment of control sites. Our findings are confirmed in experiments
      on cardiomyocyte cell cultures and supported by two-dimensional numerical
      simulations on a cross section of a rabbit ventricle.

PMID- 23005684
TI  - Topological jamming of spontaneously knotted polyelectrolyte chains driven
      through a nanopore.
AB  - The advent of solid state nanodevices allows for interrogating the
      physicochemical properties of a polyelectrolyte chain by electrophoretically
      driving it through a nanopore. Salient dynamical aspects of the translocation
      process have been recently characterized by theoretical and computational studies
      of model polymer chains free from self-entanglement. However, sufficiently long
      equilibrated chains are necessarily knotted. The impact of such topological
      "defects" on the translocation process is largely unexplored, and is addressed in
      this Letter. By using Brownian dynamics simulations on a coarse-grained
      polyelectrolyte model we show that knots, despite being trapped at the pore
      entrance, do not per se cause the translocation process to jam. Rather, knots
      introduce an effective friction that increases with the applied force, and
      practically halts the translocation above a threshold force. The predicted
      dynamical crossover, which is experimentally verifiable, ought to be relevant in
      applicative contexts, such as DNA nanopore sequencing.

PMID- 23005685
TI  - Electrical cross-correlation spectroscopy: measuring picoliter-per-minute flows
      in nanochannels.
AB  - We introduce all-electrical cross-correlation spectroscopy of molecular number
      fluctuations in nanofluidic channels. Our approach is based on a pair of nanogap
      electrochemical transducers located downstream from each other in the channel.
      When liquid is driven through this device, mesoscopic fluctuations in the local
      density of molecules are transported along the channel. We perform a time-of
      flight measurement of these fluctuations by cross-correlating current-time traces
      obtained at the two detectors. Thereby we are able to detect ultralow liquid flow
      rates below 10  pL/min. This method constitutes the electrical equivalent of
      fluorescence cross-correlation spectroscopy.

PMID- 23005686
TI  - Single-molecule study of the DNA denaturation phase transition in the force
      torsion space.
AB  - We use the "magnetic tweezers" technique to show the structural transitions that
      the DNA undergoes in the force-torsion space. In particular, we focus on the
      regions corresponding to negative supercoiling. These regions are characterized
      by the formation of the so-called denaturation bubbles, which play an essential
      role in the replication and transcription of DNA. We experimentally map the
      region of the force-torsion space where the denaturation takes place. We observe
      that large fluctuations in DNA extension occur at one of the boundaries of this
      region, i.e., when the formation of denaturation bubbles and of plectonemes
      compete. To describe the experiments, we introduce a suitable extension of the
      classical model. The model correctly describes the position of the denaturation
      regions, the transition boundaries, and the measured values of the DNA extension
      fluctuations.

PMID- 23005687
TI  - Universal relaxation governs the nonequilibrium elasticity of biomolecules.
AB  - Experimental and computational dynamic force spectroscopy is widely used to
      determine the mechanical properties of single biomolecules. Whereas so far the
      focus has mainly been on rupture or unfolding forces, recent force-probe
      molecular dynamics simulations have revealed a strong loading rate dependence of
      biomolecular elasticities, which cannot be explained by the established one
      dimensional transition-state treatments. We show that this nonequilibrium
      behavior can be explained by a theory that includes relaxation effects. For three
      structurally and mechanically quite diverse systems, a single relaxation mode
      suffices to quantitatively describe their loading-rate-dependent elastic
      behavior. Atomistic simulations of these systems revealed the microscopic nature
      of the respective relaxation modes. This result suggests a new type of
      "elasticity spectroscopy" experiment, which should render nonequilibrium
      properties of structured macromolecules accessible to single-molecule force
      spectroscopy.

PMID- 23005688
TI  - Transition from the viscous to inertial regime in dense suspensions.
AB  - Non-Brownian suspensions present a transition from Newtonian behavior in the zero
      shear limit to a shear thickening behavior at a large shear rate, none of which
      is clearly understood so far. Here, we carry out numerical simulations of such an
      athermal dense suspension under shear, at an imposed confining pressure. This
      setup is conceptually identical to recent experiments of Boyer, Guazzelli, and
      Pouliquen [Phys. Rev. Lett. 107, 188301 (2011)]. Varying the interstitial fluid
      viscosities, we recover the Newtonian and Bagnoldian regimes and show that they
      correspond to a dissipation dominated by viscous and contact forces,
      respectively. We show that the two rheological regimes can be unified as a
      function of a single dimensionless number, by adding the contributions to the
      dissipation at a given volume fraction.

PMID- 23005689
TI  - Fundamental structural constraint of random scale-free networks.
AB  - We study the structural constraint of random scale-free networks that determines
      possible combinations of the degree exponent gamma and the upper cutoff k(c) in
      the thermodynamic limit. We employ the framework of graphicality transitions
      proposed by Del Genio and co-workers [Phys. Rev. Lett. 107, 178701 (2011)], while
      making it more rigorous and applicable to general values of k(c). Using the
      graphicality criterion, we show that the upper cutoff must be lower than
      k(c)~N(1/gamma) for gamma<2, whereas any upper cutoff is allowed for gamma>2.
      This result is also numerically verified by both the random and deterministic
      sampling of degree sequences.

PMID- 23005690
TI  - Encouraging moderation: clues from a simple model of ideological conflict.
AB  - Some of the most pivotal moments in intellectual history occur when a new
      ideology sweeps through a society, supplanting an established system of beliefs
      in a rapid revolution of thought. Yet in many cases the new ideology is as
      extreme as the old. Why is it then that moderate positions so rarely prevail?
      Here, in the context of a simple model of opinion spreading, we test seven
      plausible strategies for deradicalizing a society and find that only one of them
      significantly expands the moderate subpopulation without risking its extinction
      in the process.

PMID- 23005691
TI  - Evolution of robust network topologies: emergence of central backbones.
AB  - We model the robustness against random failure or an intentional attack of
      networks with an arbitrary large-scale structure. We construct a block-based
      model which incorporates--in a general fashion--both connectivity and
      interdependence links, as well as arbitrary degree distributions and block
      correlations. By optimizing the percolation properties of this general class of
      networks, we identify a simple core-periphery structure as the topology most
      robust against random failure. In such networks, a distinct and small "core" of
      nodes with higher degree is responsible for most of the connectivity, functioning
      as a central "backbone" of the system. This centralized topology remains the
      optimal structure when other constraints are imposed, such as a given fraction of
      interdependence links and fixed degree distributions. This distinguishes simple
      centralized topologies as the most likely to emerge, when robustness against
      failure is the dominant evolutionary force.

PMID- 23005692
TI  - Comment on "density and spin response of a strongly interacting Fermi gas in the
      attractive and quasirepulsive regime".

PMID- 23005694
TI  - Comment on "electronic structure of spatially aligned graphene nanoribbons on
      Au(788)".

PMID- 23005696
TI  - Fully-automated fluorimetric determination of aluminum in seawater by in-syringe
      dispersive liquid-liquid microextraction using lumogallion.
AB  - A sensitive and selective automated in-syringe dispersive liquid-liquid
      microextraction (DLLME) method is presented. It was successfully applied to the
      determination of aluminum in coastal seawater samples. The complete analytical
      procedure including sampling, buffering, reaction of the analyte with
      fluorescence reagent lumogallion (LMG), extraction, phase separation, and
      quantification was completely automized and carried out within 4 min. DLLME was
      done using n-hexanol as an extracting solvent and ethanol as a dispersing solvent
      in a 1:8 v/v percent mixture. The Al-LMG complex was extracted by an organic
      solvent and separated from the aqueous phase within the syringe of an automated
      syringe pump. Two devices were specially developed for this work. These were (a)
      the fluorescence detector and accompanying flow cell for the organic phase
      enriched with the reaction product and (b) a heating device integrated into the
      holding coil to accelerate the slow reaction kinetics. The limits of detection
      (3sigma) and quantification (10sigma) were 8.0 +/- 0.5 nmol L(-1) and 26.7 +/-
      1.6 nmol L(-1), respectively. The relative standard deviation for eight replicate
      determinations of 200 nmol L(-1) Al(3+) was <1.5%. The calibration graph using
      the preconcentration system was linear up to 1000 nmol L(-1) with a correlation
      coefficient of 0.999. Ambient concentrations of samples were quantifiable with
      found concentrations ranging from 43 to 142 nmol L(-1). Standard additions gave
      analyte recoveries from 97% to 113% proving the general applicability and
      adequateness of the analyzer system to real sample analysis.

PMID- 23005698
TI  - Health-related quality of life in haemophilia patients with inhibitors and their
      caregivers.
AB  - Data on the health-related quality of life (HRQoL) of congenital haemophilia
      patients with inhibitors (CHwI) and their caregivers are limited. To understand
      the association between patient demo-graphics/clinical characteristics with HRQoL
      among CHwI patients and caregivers, a survey was developed to assess HRQoL with
      haemophilia-specific QoL questionnaires (HAEMO-QoL/HAEM-A-QoL). In the cross
      sectional study, paper-pencil questionnaires were mailed to 261 US CHwI
      patients/caregivers in July 2010. Descriptive analyses were performed to
      characterize HRQoL by age and to identify drivers of impairment, from both
      patient/caregiver perspectives. HRQoL scores were transformed on a scale of 0
      100, with higher scores indicating higher impairment in HRQoL. Ninety-seven
      respondents completed the HRQoL assessment. HRQoL impairment was higher in adult
      patients. In children ages 8-16 years, mean HAEMO-QoL total score was 33.8 (SD =
      15.5), and 35.0 (SD = 16.1) in children ages 4-7 years; for adult patients the
      mean HAEM-A-QoL total score was 42.2 (SD = 14.8). Adults reported highest
      impairment in the 'sports/leisure' subscale (Mean = 62.5, SD = 18.7), whereas
      patients 8-16 years reported highest impairment in the 'physical health' subscale
      (Mean = 50.8, SD = 30.5).Caregivers of patients ages 4-7 years reported greatest
      impairment within the 'family' subscale (Mean = 55.6, SD = 19.4). Caregivers were
      ''considerably/very much'' bothered by their child's inhibitors and reported
      higher QoL impairment for their child than parents who were not bothered. Within
      ChwI patients, HRQoL impairments increased with age and existed across a range of
      physical/psychosocial domains. In addition, caregiver burden also affected the
      perceived HRQoL of paediatric CHwI patients. Additional research is considered
      necessary to further understand the support caregivers need while caring for
      children with CHwI.

PMID- 23005699
TI  - Myoepithelial carcinoma of the retromolar area with extensive mandibular
      involvement.
AB  - Myoepithelial tumors were first described in 1943, and account for less than 1%
      of all salivary gland neoplasms. Their malignant variant, myoepithelial
      carcinoma, was first reported by Stromeyer et al. in 1975 and represents a very
      rare entity, characterized by distinct morphologic heterogeneity and an
      infiltrative growth pattern into adjacent tissues. However, there have been few
      reports on myoepithelial carcinoma affecting intra-oral minor salivary glands,
      and its immunohistochemical features have been poorly illustrated. We herein
      describe a rare case of myoepithelial carcinoma affecting the retromolar region
      of a 52-year-old woman that caused extensive mandibular bone destruction. We also
      reviewed the English literature concerning the involvement of intra-oral minor
      salivary glands by myoepithelial carcinoma.

PMID- 23005700
TI  - Risk factors of stroke patients admitted to a general hospital in Kuwait.
AB  - There are limited data on stroke incidence in the Middle East, and only one study
      from Kuwait. The aim of this study was to establish a baseline status of stroke
      in Kuwait. We performed a retrospective chart review of all patients admitted
      from January 1st to December 31st, 2008 to the Amiri Hospital, Kuwait, who either
      were discharged or passed away with a diagnosis of stroke. Documented risk
      factors for stroke were analyzed for the total cohort and for male and female
      subgroups. Stroke subtypes were defined in accordance with the Trial of Org 10172
      in acute stroke treatment (TOAST) criteria. There were 151 cases of stroke, of
      which 90.1% were ischemic. Eighty-five (56.3%) of the patients had diabetes
      mellitus, 86 (57.0%) had hyperlipidemia, and 104 (68.9%) had hypertension.
      Statins were used by 42.4% of the 86 hyperlipidemic patients prior to their
      presentation, and only 66 hypertensive patients (63.5%) were receiving treatment
      for hypertension prior to their presentation. Atrial fibrillation was diagnosed
      in 4% of the patients prior to their presentation, and 4% more were diagnosed
      afterward. History of ischemic heart disease was present in 28.5% of the
      subjects. This study shows similar rates of risk factors to regionally published
      reports and provides an updated picture of stroke in Kuwait.

PMID- 23005701
TI  - Hypericin-PDT-induced rapid necrotic death in human squamous cell carcinoma
      cultures after multiple treatment.
AB  - PDT (photodynamic therapy) has been used for the treatment of NMCC (non-melanoma
      cutaneous cancer) particularly, human SCC (squamous cell carcinoma). However, the
      nature of the photosensitizer, the activation light source and the mode of cell
      death induced post-PDT remains elusive. We tried to optimize PDT using the light
      activated (320-400 nm) St John's Wort-derived compound, Hyp (hypericin). The work
      highlights the potential mode of cell death and the increased efficacy of the
      technique associated with multiple Hyp-PDT treatment. SCC cells were exposed to
      different concentrations of Hyp and activated with light at 1 J/cm2 for 1 or 2
      days. Thereafter with the optimum dose of Hyp proliferation, ROS (reactive oxygen
      species), and apoptosis were analysed by XTT [2,3-bis-(2-methoxy-4-nitro-5
      sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay, FACS analysis and
      Fluorescent/Phase contrast microscopy was carried out for morphological studies.
      Hyp-PDT produces more ROS after 1 day compared with 2 days and the mode of cell
      death is a necrotic caspase-independent mechanism. We propose a novel 'double
      hit/2-day' strategy to reduce the viability in SCC using Hyp-based PDT as an
      adjunctive treatment modality.

PMID- 23005697
TI  - Association of pertussis and measles infections and immunizations with asthma and
      allergic sensitization in ISAAC Phase Two.
AB  - BACKGROUND: Pertussis and measles infection as well as vaccination have been
      suspected as possible mediating factors of allergic disease in childhood.
      METHODS: Between 1995 and 2005 cross-sectional studies were performed in 29
      centers in 21 countries. Parental questionnaires were used to collect information
      on allergic diseases and exposures. We analyzed data from 54,943 randomly
      selected schoolchildren aged 8-12 yr. A subgroup of 31,759 children was also skin
      prick tested (SPT) to common environmental allergens. Combined odds ratios were
      calculated by random effect models for meta-analysis. RESULTS: Pertussis and
      measles vaccination were not significantly associated with any of the allergy
      outcomes or SPT positivity. However, pertussis infection was associated with
      wheeze (OR(ad) 1.68; 95% CI 1.44-1.97) and rhinoconjunctivitis (OR(ad) 1.63; 95%
      1.33-2.00). Pertussis infection was also significantly associated with a higher
      prevalence of reported eczema during the past year in non-affluent countries.
      Measles infection was associated with a higher prevalence of wheeze (OR(ad) 1.26;
      95% 1.10-1.43) and reported eczema (OR(ad) 1.22; 95% 1.08-1.39). No association
      with SPT positivity was found, suggesting that these associations are unlikely to
      be mediated by an allergic component. CONCLUSIONS: Associations of pertussis and
      measles infection with symptoms of asthma, rhinoconjunctivitis and eczema were
      found in both affluent and non-affluent countries and are unlikely to be mediated
      by IgE.

PMID- 23005702
TI  - Ferrocenyl derivatives of the anthelmintic praziquantel: design, synthesis, and
      biological evaluation.
AB  - The design, synthesis, and biological evaluation of 18 ferrocenyl derivatives (4A
      12A and 4B-12B) of the most well-known drug against schistosomiasis, namely
      praziquantel (PZQ), are reported. These compounds, which have been all isolated
      as racemates, were unambiguously characterized by 1H and 13C NMR spectroscopy,
      mass spectrometry, and elemental analysis as well as by X-ray crystallography for
      4A, 5A, and 7A. Cytotoxicity studies revealed that the complexes were moderately
      toxic toward a cervical cancer cell line (HeLa) and, importantly, significantly
      less active toward a noncancerous cell line (MRC-5). The in vitro anthelmintic
      activity of the 18 ferrocenyl PZQ derivatives was tested against adult
      Schistosoma mansoni, and values in the micromolar range (26-68 MUM) were
      determined for the four most active compounds. It was also demonstrated using two
      compounds of the series as models (8A and 8B) that the complexes were stable when
      incubated for 24 h at 37  degrees C in human plasma.

PMID- 23005704
TI  - Critical manifold of the Potts model: exact results and homogeneity
      approximation.
AB  - The q-state Potts model has stood at the frontier of research in statistical
      mechanics for many years. In the absence of a closed-form solution, much of the
      past effort has focused on locating its critical manifold, trajectory in the
      parameter (q,e(J)) space where J is the reduced interaction, along which the free
      energy is singular. However, except in isolated cases, antiferromagnetic (AF)
      models with J<0 have been largely neglected. In this paper we consider the Potts
      model with AF interactions focusing on obtaining its critical manifold in exact
      and/or closed-form expressions. We first reexamine the known critical frontiers
      in light of AF interactions. For the square lattice we confirm the Potts self
      dual point to be the sole critical frontier for J>0. We also locate its critical
      frontier for J<0 and find it to coincide with a solvability condition observed by
      Baxter in 1982 [R. J. Baxter, Proc. R. Soc. London Ser. A 388, 43 (1982)]. For
      the honeycomb lattice we show that the known critical frontier holds for all J,
      and determine its critical q(c) = 1/2(3 + sqrt[5]) = 2.61803 beyond which there
      is no transition. For the triangular lattice we confirm the known critical
      frontier to hold only for J>0. More generally we consider the centered-triangle
      (CT) and Union-Jack (UJ) lattices consisting of mixed J and K interactions, and
      deduce critical manifolds under homogeneity hypotheses. For K = 0 the CT lattice
      is the diced lattice, and we determine its critical manifold for all J and find
      q(c) = 3.32472. For K = 0 the UJ lattice is the square lattice and from this we
      deduce both the J > 0 and J < 0 critical manifolds and q(c) = 3. Our theoretical
      predictions are compared with recent numerical results.

PMID- 23005703
TI  - Early attachment organization with both parents and future behavior problems:
      from infancy to middle childhood.
AB  - Links between children's attachment security with mothers and fathers, assessed
      in Strange Situation with each parent at 15 months (N = 101), and their future
      behavior problems were examined. Mothers and fathers rated children's behavior
      problems, and children reported their own behavior problems at age 8 (N = 86).
      Teachers rated behavior problems at age 61/2 (N = 86). Insecurity with both
      parents had a robust effect: "Double-insecure" children reported more overall
      problems, and were rated by teachers as having more externalizing problems than
      those secure with at least 1 parent. Security with either parent could offset
      such risks, and security with both conferred no additional benefits. High
      resistance toward both parents in Strange Situation may confer "dual risk" for
      future externalizing behavior.

PMID- 23005705
TI  - Universal construction of order parameters for translation-invariant quantum
      lattice systems with symmetry-breaking order.
AB  - For any translation-invariant quantum lattice system with a symmetry group G, we
      propose a practical and universal construction of order parameters which identify
      quantum phase transitions with symmetry-breaking order. They are defined in terms
      of the fidelity between a ground state and its symmetry-transformed counterpart,
      and are computed through tensor network representations of the ground-state wave
      function. To illustrate our scheme, we consider three quantum systems on an
      infinite lattice in one spatial dimension, namely, the quantum Ising model in a
      transverse magnetic field, the quantum spin-1/2XYX model in an external magnetic
      field, and the quantum spin-1 XXZ model with single-ion anisotropy. All these
      models have symmetry group Z(2) and exhibit broken-symmetry phases. We also
      discuss the role of the order parameters in identifying factorized states.

PMID- 23005706
TI  - Dissipation in quasistatically sheared wet and dry sand under confinement.
AB  - We investigated the stress-strain behavior of sand with and without small amounts
      of liquid under steady and oscillatory shear. Since dry sand has a lower shear
      modulus, one would expect it to deform more easily. Using a new technique to
      quasistatically push the sand through a tube with an enforced parabolic
      (Poiseuille-like) profile, we minimize the effect of avalanches and shear
      localization. We observe that the resistance against deformation of the wet
      (partially saturated) sand is much smaller than that of the dry sand, and that
      the latter dissipates more energy under flow. This is also observed in large
      amplitude oscillatory shear measurements using a rotational rheometer, showing
      that the effect is robust and holds for different types of flow.

PMID- 23005617
TI  - Measurement of the electron charge asymmetry in inclusive W production in pp
      collisions at sqrt[s]=7  TeV.
AB  - A measurement of the electron charge asymmetry in inclusive pp->W+X->enu+X
      production at sqrt[s]=7  TeV is presented based on data recorded by the CMS
      detector at the LHC and corresponding to an integrated luminosity of 840  pb(-1).
      The electron charge asymmetry reflects the unequal production of W(+) and W(-)
      bosons in pp collisions. The electron charge asymmetry is measured in bins of the
      absolute value of electron pseudorapidity in the range of |eta|<2.4. The
      asymmetry rises from about 0.1 to 0.2 as a function of the pseudorapidity and is
      measured with a relative precision better than 7%. This measurement provides new
      stringent constraints for parton distribution functions.

PMID- 23005707
TI  - Sphere impact and penetration into wet sand.
AB  - We present experimental results for the penetration of a solid sphere when
      released onto wet sand. We show, by measuring the final penetration depth, that
      the cohesion induced by the water can result in either a deeper or shallower
      penetration for a given release height compared to dry granular material. Thus
      the presence of water can either lubricate or stiffen the granular material. By
      assuming the shear rate is proportional to the impact velocity and using the
      depth-averaged stopping force in calculating the shear stress, we derive
      effective viscosities for the wet granular materials.

PMID- 23005708
TI  - Time dependence and density inversion in simulations of vertically oscillated
      granular layers.
AB  - We study a layer of grains atop a plate which oscillates sinusoidally in the
      direction of gravity, using three-dimensional, time-dependent numerical solutions
      of continuum equations to Navier-Stokes order as well as hard-sphere molecular
      dynamics simulations. For high accelerational amplitudes of the plate, the layer
      exhibits a steady-state "density inversion" in which a high-density portion of
      the layer is supported by a lower-density portion. At low accelerational
      amplitudes, the layer exhibits oscillatory time dependence that is strongly
      correlated to the motion of the plate. We show that continuum simulations yield
      results consistent with molecular dynamics results in both regimes.

PMID- 23005709
TI  - Molecular dynamics simulation of the Johari-Goldstein relaxation in a molecular
      liquid.
AB  - Molecular dynamics simulations were carried out to investigate the
      reorientational motion of a rigid (fixed bond length), asymmetric diatomic
      molecule in the liquid and glassy states. In the latter the molecule reorients
      via large-angle jumps, which we identify with the Johari-Goldstein (JG) dynamics.
      This relaxation process has a broad distribution of relaxation times, and at
      least deeply in the glassy state, the mobility of a given molecule remains fixed
      over time; that is, there is no dynamic exchange among molecules. Interestingly,
      the JG relaxation time for a molecule does not depend on the local density,
      although the nonergodicity factor is weakly correlated with the packing
      efficiency of neighboring molecules. In the liquid state the intensity of the JG
      process increases significantly, eventually subsuming the slower alpha
      relaxation. This evolution of the JG motion into structural relaxation underlies
      the correlation of many properties of the JG and alpha dynamics.

PMID- 23005711
TI  - Field-induced transitions between multilayer phases of polar smectic liquid
      crystals.
AB  - Recently Wang et al. [Phys. Rev. Lett. 104, 027801 (2010)] reported the discovery
      of a novel multilayer phase in polar liquid crystals. The phase was unambiguously
      assigned to a six-layer antiferroelectric structure (Sm-C(d6)(*)) by resonant x
      ray diffraction. This discovery lead to essential progress in understanding the
      nature of polar phases. However, more recently, Chandani et al. [Liq. Cryst. 38,
      663 (2011)] in the same material clearly identified the novel phase as a
      ferrielectric five-layer structure (Sm-C(d5)(*)) by the electric-field-induced
      birefringence. This contradiction seemed to be a mystery. In this paper we show
      that the two experiments are in agreement. Phenomenological Landau theory of the
      phase transitions shows that both phases (Sm-C(d6)(*) and Sm-C(d5)(*)) exist and
      transform into each other in a relatively low electric field.

PMID- 23005710
TI  - Imbibition of a textured surface decorated by short pillars with rounded edges.
AB  - Imbibition of micropatterned surfaces can have broad technological and
      fundamental implications for areas ranging from biomedical devices and fuel
      transport to writing with ink. Despite rapidly growing interests aimed at various
      applications, a fundamental physical understanding of the imbibition dynamics is
      still in its infancy. Recently, two simple scaling regimes for the dynamics have
      been established for a textured surface decorated with long pillars whose top and
      bottom edges are sharp. Here, we study the imbibition dynamics of textured
      surfaces decorated by short pillars with rounded edges, to find a different
      scaling regime. Interestingly, this regime originates not from the balance of two
      effects but from the hybrid balance of three effects. Furthermore, this scaling
      law can be universal or independent of the details of the texture geometry. We
      envision that this potentially universal scaling regime might be ubiquitous and
      will be useful in the handling and transportation of a small amount of liquid.

PMID- 23005712
TI  - Antinematic orientational order produced by an extreme case of the generalized
      Straley lattice model.
AB  - We address here a special, extreme case of the quadratic pair interaction
      potential between classical, D(2h)-symmetric particles (the generalized Straley
      model) on a three-dimensional simple cubic lattice. The model involves
      predominant antinematic couplings and it has been studied by Monte Carlo
      simulation and a molecular field treatment. The obtained results show a second
      order transition between the isotropic phase and the low-temperature one,
      exhibiting uniaxial antinematic order.

PMID- 23005713
TI  - Geodesic defect anchoring on nematic shells.
AB  - Nematic shells are colloidal particles coated with nematic liquid crystal
      molecules, which may freely glide and rotate on the colloid's surface while
      keeping their long axis on the local tangent plane. Molecular dynamics
      simulations on a nanoscopic spherical shell indicate that under appropriate
      adhesion conditions for the molecules on the equator, the equilibrium nematic
      texture exhibits at each pole a pair of +1/2 defects so close to one another to
      be treated as one +1 defect. Spirals connect the polar defects, though the
      continuum limit of the interaction potential would not feature any elastic
      anisotropy. A molecular averaging justifies an anchoring defect energy that feels
      the geodesics emanating from the defect. All our observations are explained by
      such a geodesic anchoring, which vanishes on flat manifolds.

PMID- 23005714
TI  - Biaxial nematic order induced by smectic fluctuations.
AB  - We report on a series of measurements on the microscopic structure and the
      magneto-optical properties of a calamitic liquid crystalline compound in its
      nematic phase. Structural studies show the existence of short-range, tilted
      smectic order consistent with pretransitional effects above an underlying smectic
      phase. Concomitantly, magneto-optical results exhibit the existence of an optic
      axis not collinear with the uniaxial director. This apparent biaxial nature is
      discussed within the context of coupling between the tensor nematic and the
      smectic order parameters.

PMID- 23005715
TI  - Defect trajectories in nematic shells: role of elastic anisotropy and thickness
      heterogeneity.
AB  - We introduce the idea of transformation trajectories to describe the evolution of
      nematic shells in terms of defect locations and director field when the elastic
      anisotropy and the shell thickness heterogeneity vary. Experiments are compared
      to numerical results to clarify the exact role played by these two parameters. We
      demonstrate that heterogeneity in thickness is a result of a symmetry breaking
      initiated by buoyancy and enhanced by liquid crystal elasticity, and is
      irrespective of the elastic anisotropy. In contrast, elastic anisotropy--in
      particular, disfavored bend distortion--drives an asymmetric defect
      reorganization. These shell states can be both stable or metastable.

PMID- 23005717
TI  - Phase diagram and quench dynamics of the cluster-XY spin chain.
AB  - We study the complete phase space and the quench dynamics of an exactly solvable
      spin chain, the cluster-XY model. In this chain, the cluster term and the XY
      couplings compete to give a rich phase diagram. The phase diagram is studied by
      means of the quantum geometric tensor. We study the time evolution of the system
      after a critical quantum quench using the Loschmidt echo. The structure of the
      revivals after critical quantum quenches presents a nontrivial behavior depending
      on the phase of the initial state and the critical point.

PMID- 23005716
TI  - Nonequilibrium fluctuations of a remodeling in vitro cytoskeleton.
AB  - Motor proteins actively contract the actin cytoskeleton of cells and thereby give
      rise to nonequilibrium fluctuations as well as changes in the architecture of the
      cytoskeleton. Here, we show, by video microrheology of a reconstituted
      cytoskeleton, that motors generate time-dependent nonequilibrium fluctuations,
      which evolve as the network is remodeled. At earlier times, the fluctuation
      spectrum is dominated by strong non-Gaussian fluctuations, which arise from large
      displacements. At later times, directed displacements are infrequent and finally
      disappear. We show that these effects are due to contractile coarsening of the
      network into large actin-myosin foci.

PMID- 23005718
TI  - Crossover from isotropic to directed percolation.
AB  - We generalize the directed percolation (DP) model by relaxing the strict
      directionality of DP such that propagation can occur in either direction but with
      anisotropic probabilities. We denote the probabilities as p(?) = pp(d) and p(?) =
      p(1-p(d)), with p representing the average occupation probability and p(d)
      controlling the anisotropy. The Leath-Alexandrowicz method is used to grow a
      cluster from an active seed site. We call this model with two main growth
      directions biased directed percolation (BDP). Standard isotropic percolation (IP)
      and DP are the two limiting cases of the BDP model, corresponding to p(d) =1/2
      and p(d) = 0,1 respectively. In this work, besides IP and DP, we also consider
      the 1/2 < p(d) <1 region. Extensive Monte Carlo simulations are carried out on
      the square and the simple-cubic lattices, and the numerical data are analyzed by
      finite-size scaling. We locate the percolation thresholds of the BDP model for
      p(d) = 0.6 and 0.8, and determine various critical exponents. These exponents are
      found to be consistent with those for standard DP. We also determine the
      renormalization exponent associated with the asymmetric perturbation due to p(d)
      1/2 ? 0 near IP, and confirm that such an asymmetric scaling field is relevant at
      IP.

PMID- 23005719
TI  - Reverse preferential spread in complex networks.
AB  - Large-degree nodes may have a larger influence on the network, but they can be
      bottlenecks for spreading information since spreading attempts tend to
      concentrate on these nodes and become redundant. We discuss that the reverse
      preferential spread (distributing information inversely proportional to the
      degree of the receiving node) has an advantage over other spread mechanisms. In
      large uncorrelated networks, we show that the mean number of nodes that receive
      information under the reverse preferential spread is an upper bound among any
      other weight-based spread mechanisms, and this upper bound is indeed a logistic
      growth independent of the degree distribution.

PMID- 23005720
TI  - Multifractality of eigenfunctions in spin chains.
AB  - We investigate different one-dimensional quantum spin-1/2 chain models, and by
      combining analytical and numerical calculations we prove that their ground state
      wave functions in the natural spin basis are multifractals with, in general,
      nontrivial fractal dimensions.

PMID- 23005721
TI  - Weak correlation effects in the Ising model on triangular-tiled hyperbolic
      lattices.
AB  - The Ising model is studied on a series of hyperbolic two-dimensional lattices
      which are formed by tessellation of triangles on negatively curved surfaces. In
      order to treat the hyperbolic lattices, we propose a generalization of the corner
      transfer matrix renormalization group method using a recursive construction of
      asymmetric transfer matrices. Studying the phase transition, the mean-field
      universality is captured by means of a precise analysis of thermodynamic
      functions. The correlation functions and the density-matrix spectra always decay
      exponentially even at the transition point, whereas power-law behavior
      characterizes criticality on the Euclidean flat geometry. We confirm the absence
      of a finite correlation length in the limit of infinite negative Gaussian
      curvature.

PMID- 23005722
TI  - Probabilities for large events in driven threshold systems.
AB  - Many driven threshold systems display a spectrum of avalanche event sizes, often
      characterized by power-law scaling. An important problem is to compute
      probabilities of the largest events ("Black Swans"). We develop a data-driven
      approach to the problem by transforming to the event index frame, and relating
      this to Shannon information. For earthquakes, we find the 12-month probability
      for magnitude m>6 earthquakes in California increases from about 30% after the
      last event, to 40%-50% prior to the next one.

PMID- 23005723
TI  - Nonequilibrium fluctuation theorem for systems under discrete and continuous
      feedback control.
AB  - In the time reverse process of a feedback manipulated stochastic system, we allow
      performing measurements without violating causality. As a result we come across
      an entropy production due to the measurement process. This entropy production, in
      addition to the usual system and medium entropy production, constitutes the total
      entropy production of the combined system of the reservoir, the system, and the
      feedback controller. We show that this total entropy production of "full" system
      satisfies an integrated fluctuation theorem as well as a detailed fluctuation
      theorem as expected. We illustrate and verify this idea through explicit
      calculation and direct simulation in two examples.

PMID- 23005724
TI  - First-passage time for subdiffusion: the nonadditive entropy approach versus the
      fractional model.
AB  - We study the similarities and differences between different models concerning
      subdiffusion. More particularly, we calculate first passage time (FPT)
      distributions for subdiffusion, derived from Greens' functions of nonlinear
      equations obtained from Sharma-Mittal's, Tsallis's, and Gauss's nonadditive
      entropies. Then we compare these with FPT distributions calculated from a
      fractional model using a subdiffusion equation with a fractional time derivative.
      All of Greens' functions give us exactly the same standard relation ((Deltax)(2)
      )=2D(alpha)t(alpha) which characterizes subdiffusion (0 < alpha <1), but
      generally FPT distributions are not equivalent to one another. We will show here
      that the FPT distribution for the fractional model is asymptotically equal to the
      Sharma-Mittal model over the long time limit only if in the latter case one of
      the three parameters describing Sharma-Mittal entropy r depends on alpha, and
      satisfies the specific equation derived in this paper, whereas the other two
      models mentioned above give different FPT distributions with the fractional
      model. Greens' functions obtained from the Sharma-Mittal and fractional models,
      for r obtained from this particular equation, are very similar to each other. We
      will also discuss the interpretation of subdiffusion models based on nonadditive
      entropies and the possibilities of the experimental measurement of subdiffusion
      models' parameters.

PMID- 23005725
TI  - Noncanonical statistics of a spin-boson model: theory and exact Monte Carlo
      simulations.
AB  - Equilibrium canonical distribution in statistical mechanics assumes weak system
      bath coupling (SBC). In real physical situations this assumption can be invalid,
      and equilibrium quantum statistics of the system may be noncanonical. By
      exploiting both polaron transformation and perturbation theory in a spin-boson
      model, an analytical treatment is advocated to study noncanonical statistics of a
      two-level system at arbitrary temperature and for arbitrary SBC strength,
      yielding theoretical results in agreement with exact Monte Carlo simulations. In
      particular, the eigen-representation of system's reduced density matrix is used
      to quantify noncanonical statistics as well as the quantumness of the open
      system. For example, it is found that irrespective of SBC strength, noncanonical
      statistics enhances as temperature decreases but vanishes at high temperature.

PMID- 23005726
TI  - Random collisions on branched networks: how simultaneous diffusion prevents
      encounters in inhomogeneous structures.
AB  - A huge variety of natural phenomena, including prey-predator interaction,
      chemical reaction kinetics, foraging, and pharmacokinetics, are mathematically
      described as encounters between entities performing a random motion on an
      appropriate structure. On homogeneous structures, two random walkers meet with
      certainty if and only if the structure is recurrent, i.e., a single random walker
      returns to its starting point with probability 1. We prove here that this
      property does not hold on general inhomogeneous structures, and introduce the
      concept of two-particle transience, providing examples of realistic recurrent
      structures where two particles may never meet if they both move, while an
      encounter is certain if either stays put. We anticipate that our results will
      pave the way for the study of the effects of geometry in a wide array of natural
      phenomena involving interaction between randomly moving agents.

PMID- 23005727
TI  - Brownian transport in corrugated channels with inertia.
AB  - Transport of suspended Brownian particles dc driven along corrugated narrow
      channels is numerically investigated in the regime of finite damping. We show
      that inertial corrections cannot be neglected as long as the width of the channel
      bottlenecks is smaller than an appropriate particle diffusion length, which
      depends on the the channel corrugation and the drive intensity. With such a
      diffusion length being inversely proportional to the damping constant, transport
      through sufficiently narrow obstructions turns out to be always sensitive to the
      viscosity of the suspension fluid. The inertia corrections to the transport
      quantifiers, mobility, and diffusivity markedly differ for smoothly and sharply
      corrugated channels.

PMID- 23005728
TI  - Fractional-time random walk subdiffusion and anomalous transport with finite mean
      residence times: faster, not slower.
AB  - Continuous time random walk (CTRW) subdiffusion along with the associated
      fractional Fokker-Planck equation (FFPE) is traditionally based on the premise of
      random clock with divergent mean period. This work considers an alternative CTRW
      and FFPE description which is featured by finite mean residence times (MRTs) in
      any spatial domain of finite size. Transient subdiffusive transport can occur on
      a very large time scale tau(c) which can greatly exceed mean residence time in
      any trap, tau(c) >>(tau), and even not being related to it. Asymptotically, on a
      macroscale transport becomes normal for t >> tau(c). However, mesoscopic
      transport is anomalous. Differently from viscoelastic subdiffusion no long-range
      anticorrelations among position increments are required. Moreover, our study
      makes it obvious that the transient subdiffusion and transport are faster than
      one expects from their normal asymptotic limit on a macroscale. This observation
      has profound implications for anomalous mesoscopic transport processes in
      biological cells because the macroscopic viscosity of cytoplasm is finite.

PMID- 23005729
TI  - Thermodynamic phase transitions for Pomeau-Manneville maps.
AB  - We study phase transitions in the thermodynamic description of Pomeau-Manneville
      intermittent maps from the point of view of infinite ergodic theory, which deals
      with diverging measure dynamical systems. For such systems, we use a
      distributional limit theorem to provide both a powerful tool for calculating
      thermodynamic potentials as also an understanding of the dynamic characteristics
      at each instability phase. In particular, topological pressure and Renyi entropy
      are calculated exactly for such systems. Finally, we show the connection of the
      distributional limit theorem with non-Gaussian fluctuations of the algorithmic
      complexity proposed by Gaspard and Wang [Proc. Natl. Acad. Sci. USA 85, 4591
      (1988)].

PMID- 23005730
TI  - Virial expansion coefficients in the harmonic approximation.
AB  - The virial expansion method is applied within a harmonic approximation to an
      interacting N-body system of identical fermions. We compute the canonical
      partition functions for two and three particles to get the two lowest orders in
      the expansion. The energy spectrum is carefully interpolated to reproduce ground
      state properties at low temperature and the noninteracting high-temperature limit
      of constant virial coefficients. This resembles the smearing of shell effects in
      finite systems with increasing temperature. Numerical results are discussed for
      the second and third virial coefficients as functions of dimension, temperature,
      interaction, and transition temperature between low- and high-energy limits.

PMID- 23005731
TI  - Heat exchange mediated by a quantum system.
AB  - We consider heat transfer between two thermal reservoirs mediated by a quantum
      system using the generalized quantum Langevin equation. The thermal reservoirs
      are treated as ensembles of oscillators within the framework of the Drude
      Ullersma model. General expressions for the heat current and thermal conductance
      are obtained for arbitrary coupling strength between the reservoirs and the
      mediator and for different temperature regimes. As an application of these
      results we discuss the origin of Fourier's law in a chain of large but finite
      subsystems coupled to each other by the quantum mediators. We also address a
      question of anomalously large heat current between the scanning tunneling
      microscope (STM) tip and substrate found in a recent experiment. The question of
      minimum thermal conductivity is revisited in the framework of scaling theory as a
      potential application of the developed approach.

PMID- 23005732
TI  - Anomalous diffusion in run-and-tumble motion.
AB  - A random walk scheme, consisting of alternating phases of regular Brownian motion
      and Levy walks, is proposed as a model for run-and-tumble bacterial motion.
      Within the continuous-time random walk approach we obtain the long-time and short
      time behavior of the mean squared displacement of the walker as depending on the
      properties of the dwelling time distribution in each phase. Depending on these
      distributions, normal diffusion, superdiffusion, and ballistic spreading may
      arise.

PMID- 23005733
TI  - Spatiotemporal bounded noises and transitions induced by them in solutions of the
      real Ginzburg-Landau model.
AB  - In this work, we introduce two spatiotemporal colored bounded noises, based on
      the zero-dimensional Cai-Lin and Tsallis-Borland noises. Then we study and
      characterize the dependence of the defined stochastic processes on both a
      temporal correlation parameter tau and a spatial coupling parameter lambda. In
      particular, we found that varying lambda may induce a transition of the
      distribution of the noise from bimodality to unimodality. With the aim of
      investigating the role played by bounded noises in nonlinear dynamical systems,
      we analyze the behavior of the real Ginzburg-Landau time-varying model additively
      perturbed by such noises. The observed phase transition phenomenology is quite
      different from that observed when the perturbations are unbounded. In particular,
      we observed an inverse order-to-disorder transition and a reentrant transition,
      with dependence on the specific type of bounded noise.

PMID- 23005734
TI  - Double resonance in the infinite-range quantum Ising model.
AB  - We study quantum resonance behavior of the infinite-range kinetic Ising model at
      zero temperature. Numerical integration of the time-dependent Schrodinger
      equation in the presence of an external magnetic field in the z direction is
      performed at various transverse field strengths g. It is revealed that two
      resonance peaks occur when the energy gap matches the external driving frequency
      at two distinct values of g, one below and the other above the quantum phase
      transition. From the similar observations already made in classical systems with
      phase transitions, we propose that the double resonance peaks should be a generic
      feature of continuous transitions, for both quantum and classical many-body
      systems.

PMID- 23005735
TI  - Kinetic theory for systems of self-propelled particles with metric-free
      interactions.
AB  - A model of self-driven particles similar to the Vicsek model [Phys. Rev. Lett.
      75, 1226 (1995)] but with metric-free interactions is studied by means of a novel
      Enskog-type kinetic theory. In this model, N particles of constant speed v(0) try
      to align their travel directions with the average direction of a fixed number of
      closest neighbors. At strong alignment a global flocking state forms. The
      alignment is defined by a stochastic rule, not by a Hamiltonian. The
      corresponding interactions are of genuine multibody nature. The theory is based
      on a Master equation in 3N-dimensional phase space, which is made tractable by
      means of the molecular chaos approximation. The phase diagram for the transition
      to collective motion is calculated and compared to direct numerical simulations.
      A linear stability analysis of a homogeneous ordered state is performed using the
      kinetic but not the hydrodynamic equations in order to achieve high accuracy. In
      contrast to the regular metric Vicsek-model no instabilities occur. This confirms
      previous direct simulations that, for Vicsek-like models with metric-free
      interactions, there is no formation of density bands and that the flocking
      transition is continuous.

PMID- 23005736
TI  - Analytical results for long-time behavior in anomalous diffusion.
AB  - We investigate through a generalized Langevin formalism the phenomenon of
      anomalous diffusion for asymptotic times, and we generalized the concept of the
      diffusion exponent. A method is proposed to obtain the diffusion coefficient
      analytically through the introduction of a time scaling factor lambda. We obtain
      as well an exact expression for lambda for all kinds of diffusion. Moreover, we
      show that lambda is a universal parameter determined by the diffusion exponent.
      The results are then compared with numerical calculations and very good agreement
      is observed. The method is general and may be applied to many types of stochastic
      problem.

PMID- 23005737
TI  - Active-to-absorbing-state phase transition in the presence of fluctuating
      environments: weak and strong dynamic scaling.
AB  - We investigate the scaling properties of phase transitions between survival and
      extinction (active-to-absorbing-state phase transition, AAPT) in a model that by
      itself belongs to the directed percolation (DP) universality class, interacting
      with a spatiotemporally fluctuating environment having its own nontrivial
      dynamics. We model the environment by (i) a randomly stirred fluid, governed by
      the Navier-Stokes (NS) equation, and (ii) a fluctuating surface, described either
      by the Kardar-Parisi-Zhang (KPZ) or the Edward-Wilkinson (EW) equations. We show,
      by using a one-loop perturbative field theoretic setup that, depending upon the
      spatial scaling of the variance of the external forces that drive the environment
      (i.e., the NS, KPZ, or EW equations), the system may show weak or strong dynamic
      scaling at the critical point of active-to-absorbing-state phase transitions. In
      the former case AAPT displays scaling belonging to the DP universality class,
      whereas in the latter case the universal behavior is different.

PMID- 23005738
TI  - Subdiffusion in a system with thin membranes.
AB  - We study both theoretically and experimentally a process of subdiffusion in a
      system with two thin membranes. The theoretical model uses Green's functions
      obtained for the membrane system by means of the generalized method of images.
      These Green's functions are combinations of the fundamental solutions to a
      fractional subdiffusion equation describing subdiffusion in a homogenous,
      unbounded system. Using Green's functions we find analytical formulas describing
      the time evolution of concentration profiles and the time evolution of the amount
      of substance that remains in the region between the membranes. The concentration
      profiles fulfill a new boundary condition at the membrane, in which the membrane
      permeability is assumed to change over time according to the special formula
      presented in the paper. These concentration profiles fulfill a standard
      subdiffusion equation with fractional Riemann-Liouville time derivative only
      approximately, but they coincide very well with the experimental data. Fitting
      the theoretical functions in with the experimental results, we also estimate the
      subdiffusion coefficient of polyethylene glycol 2000 in agarose hydrogel.

PMID- 23005739
TI  - Scaling behavior for a class of quantum phase transitions.
AB  - We show that for quantum phase transitions with a single bosonic zero mode at the
      critical point, like the Dicke model and the Lipkin-Meshkov-Glick model, metric
      quantities such as fidelity, that is, the overlap between two ground states
      corresponding to two values lambda(1) and lambda(2) of the controlling parameter
      lambda, depend only on the ratio eta = (lambda(1) -lambda(c))/(lambda(2) 
      lambda(c)), where lambda = lambda(c) at the critical point. This scaling property
      is valid also for time-dependent quantities such as the Loschmidt echo, provided
      time is measured in units of the inverse frequency of the critical mode.

PMID- 23005740
TI  - Potts and percolation models on bowtie lattices.
AB  - We give the exact critical frontier of the Potts model on bowtie lattices. For
      the case of q = 1, the critical frontier yields the thresholds of bond
      percolation on these lattices, which are exactly consistent with the results
      given by Ziff et al. [J. Phys. A 39, 15083 (2006)]. For the q = 2 Potts model on
      a bowtie A lattice, the critical point is in agreement with that of the Ising
      model on this lattice, which has been exactly solved. Furthermore, we do
      extensive Monte Carlo simulations of the Potts model on a bowtie A lattice with
      noninteger q. Our numerical results, which are accurate up to seven significant
      digits, are consistent with the theoretical predictions. We also simulate the
      site percolation on a bowtie A lattice, and the threshold is s(c) = 0.5479148(7).
      In the simulations of bond percolation and site percolation, we find that the
      shape-dependent properties of the percolation model on a bowtie A lattice are
      somewhat different from those of an isotropic lattice, which may be caused by the
      anisotropy of the lattice.

PMID- 23005741
TI  - Thermodynamics of dipolar hard spheres with low-to-intermediate coupling
      constants.
AB  - The thermodynamic properties of the dipolar hard-sphere fluid are studied using
      theory and simulation. A new theory is derived using a convenient mathematical
      approximation for the Helmholtz free energy relative to that for the hard-sphere
      fluid. The approximation is designed to give the correct low-density virial
      expansion. New theoretical and numerical results for the fourth virial
      coefficient are given. Predictions of thermodynamic functions for dipolar
      coupling constants lambda=1 and 2 show excellent agreement with simulation
      results, even at the highest value of the particle volume fraction phi. For
      higher values of lambda, there are deviations at high volume fractions, but the
      correct low-density behavior is retained. The theory is compared critically
      against the established thermodynamic perturbation theory; it gives significant
      improvements at low densities and is more convenient in terms of the required
      numerics. Dipolar hard spheres provide a basic model for ferrofluids, and the
      theory is accurate for typical experimental parameters lambda </~ 2 and phi </~
      0.1. This is demonstrated explicitly by fitting osmotic equations of state for
      real ferrofluids measured recently by analytical centrifugation.

PMID- 23005742
TI  - Entropy production from stochastic dynamics in discrete full phase space.
AB  - The stochastic entropy generated during the evolution of a system interacting
      with an environment may be separated into three components, but only two of these
      have a non-negative mean. The third component of entropy production is associated
      with the relaxation of the system probability distribution towards a stationary
      state and with nonequilibrium constraints within the dynamics that break detailed
      balance. It exists when at least some of the coordinates of the system phase
      space change sign under time reversal, and when the stationary state is
      asymmetric in these coordinates. We illustrate the various components of entropy
      production, both in detail for particular trajectories and in the mean, using
      simple systems defined on a discrete phase space of spatial and velocity
      coordinates. These models capture features of the drift and diffusion of a
      particle in a physical system, including the processes of injection and removal
      and the effect of a temperature gradient. The examples demonstrate how entropy
      production in stochastic thermodynamics depends on the detail that is included in
      a model of the dynamics of a process. Entropy production from such a perspective
      is a measure of the failure of such models to meet Loschmidt's expectation of
      dynamic reversibility.

PMID- 23005743
TI  - Identification of noisy response latency.
AB  - In many physical systems there is a time delay before an applied input
      (stimulation) has an impact on the output (response), and the quantification of
      this delay is of paramount interest. If the response can only be observed on top
      of an indistinguishable background signal, the estimation can be highly
      unreliable, unless the background signal is accounted for in the analysis. In
      fact, if the background signal is ignored, however small it is compared to the
      response and however large the delay is, the estimate of the time delay will go
      to zero for any reasonable estimator when increasing the number of observations.
      Here we propose a unified concept of response latency identification in event
      data corrupted by a background signal. It is done in the context of information
      transfer within a neural system, more specifically on spike trains from single
      neurons. The estimators are compared on simulated data and the most suitable for
      specific situations are recommended.

PMID- 23005744
TI  - Single-file diffusion in a box: effect of the initial configuration.
AB  - This paper studies the single-file diffusion process on a linear chain of
      identical pointlike particles with multiple-site occupation confined in a one
      dimensional box. The particles are noninteracting, except that double occupancy
      is forbidden. When particles are confined in a finite box, the final stage is
      saturation. By means of combinatorial analysis, an exact numerical evaluation of
      the saturation values for both the mean-square displacement (MSD) of a tracer
      particle and the center of mass of the system are obtained. Different initial
      distributions of particles are introduced. The time dependence of the MSD is
      obtained by means of Monte Carlo simulations. The values of the MSD for the
      tracer particles as well as the center of mass of the system depend on the size
      of the particle, the size of the box, and the initial distribution. Moreover, the
      transient regime depends on the initial distribution. In fact, the crossover from
      normal to subdiffusive regime is observed for random and alternate initial
      distributions, while superdiffusive diffusion appears for any stacked initial
      distributions. In all cases, it is shown that the collisions between particles do
      not determine the time exponent of the MSD. A simple expression for the transient
      regime is also obtained for the especial case of random initial distribution.

PMID- 23005745
TI  - Thermodynamic curvature from the critical point to the triple point.
AB  - I evaluate the thermodynamic curvature R for fourteen pure fluids along their
      liquid-vapor coexistence curves, from the critical point to the triple point,
      using thermodynamic input from the NIST Chemistry WebBook. In this broad
      overview, R is evaluated in both the coexisting liquid and vapor phases. R is an
      invariant whose magnitude |R| is a measure of the size of mesoscopic organized
      structures in a fluid, and whose sign specifies whether intermolecular
      interactions are effectively attractive (R<0) or repulsive (R>0). I discuss five
      principles for R in pure fluids: (1) Near the critical point, the attractive part
      of the interactions forms loose structures of size |R| proportional to the
      correlation volume xi(3), and the sign of R is negative. (2) In the vapor phase,
      there are instances of compact clusters of size |R| formed by the attractive part
      of the interactions and prevented from collapse by the repulsive part of the
      interactions, and the sign of R is positive. (3) In the asymptotic critical point
      regime, the R's in the coexisting liquid and vapor phases are equal to each
      other, i.e., commensurate. (4) Outside the asymptotic critical-point regime
      incommensurate R's may be associated with metastability. (5) The compact liquid
      phase has |R| on the order of the volume of a molecule, with the sign of R being
      negative for a liquidlike state held together by attractive interactions and the
      sign of R being positive for a solidlike state held up by repulsive interactions.
      These considerations amplify and extend the application of thermodynamic
      curvature in pure fluids.

PMID- 23005746
TI  - Random-field and random-anisotropy O(N) spin systems with a free surface.
AB  - We study the surface scaling behavior of a semi-infinite d-dimensional O(N) spin
      system in the presence of a quenched random field and random anisotropy
      disorders. It is known that above the lower critical dimension d(LC) = 4 the
      infinite models undergo a paramagnetic-ferromagnetic transition for N > N(c)
      (N(c) = 2.835 for the random field and N(c) =9.441 for random anisotropy). For N
      < N(c) and d < d(LC) there exists a quasi-long-range-order phase with a zero
      order parameter and a power-law decay of spin correlations. Using a functional
      renormalization group, we derive the surface scaling laws that describe the
      ordinary surface transition for d > d(LC) and the long-range behavior of spin
      correlations near the surface in the quasi-long-range-order phase for d < d(LC).
      The corresponding surface exponents are calculated to one-loop order. The
      obtained results can be applied to the surface scaling of periodic elastic
      systems in disordered media, amorphous magnets, and (3)He-A in aerogel.

PMID- 23005747
TI  - Equilibrium properties of quantum spin systems with nonadditive long-range
      interactions.
AB  - We study equilibrium states of quantum spin systems with nonadditive long-range
      interactions by adopting an appropriate scaling of the interaction strength,
      i.e., the so-called Kac prescription. In classical spin systems, it is known that
      the equilibrium free energy is obtained by minimizing the free-energy functional
      over the coarse-grained magnetization. Here we show that it is also true for
      quantum spin systems. From this observation, it is found that when the canonical
      ensemble and the microcanonical ensemble are not equivalent in some parameter
      region, it is not necessarily justified to replace the actual long-range
      interaction by the infinite-range interaction (Curie-Weiss-type interaction). On
      the other hand, in the parameter region where the two ensembles are equivalent,
      this replacement is always justified. We examine the Heisenberg XXZ model as an
      illustrative example and discuss the relation to experiments.

PMID- 23005748
TI  - Performance of a multilevel quantum heat engine of an ideal N-particle Fermi
      system.
AB  - We generalize the quantum heat engine (QHE) model which was first proposed by
      Bender et al. [J. Phys. A 33, 4427 (2000)] to the case in which an ideal Fermi
      gas with an arbitrary number N of particles in a box trap is used as the working
      substance. Besides two quantum adiabatic processes, the engine model contains two
      isoenergetic processes, during which the particles are coupled to energy baths at
      a high constant energy E(h) and a low constant energy E(c), respectively.
      Directly employing the finite-time thermodynamics, we find that the power output
      is enhanced by increasing particle number N (or decreasing minimum trap size
      L(A)) for given L(A) (or N), without reduction in the efficiency. By use of
      global optimization, the efficiency at possible maximum power output (EPMP) is
      found to be universal and independent of any parameter contained in the engine
      model. For an engine model with any particle-number N, the efficiency at maximum
      power output (EMP) can be determined under the condition that it should be
      closest to the EPMP. Moreover, we extend the heat engine to a more general
      multilevel engine model with an arbitrary 1D power-law potential. Comparison
      between our engine model and the Carnot cycle shows that, under the same
      conditions, the efficiency eta = 1 - E(c)/E(h) of the engine cycle is bounded
      from above the Carnot value eta(c) =1 - T(c)/T(h).

PMID- 23005749
TI  - Topological phase transition in the Scheidegger model of river networks.
AB  - Transport networks are found at the heart of myriad natural systems, yet are
      poorly understood, except for the case of river networks. The Scheidegger model,
      in which rivers are convergent random walks, has been studied only in the case of
      flat topography, ignoring the variety of curved geometries found in nature.
      Embedding this model on a cone, we find a convergent and a divergent phase,
      corresponding to few, long basins and many, short basins, respectively, separated
      by a singularity, indicating a phase transition. Quantifying basin shape using
      Hacks law l ~ a(h) gives distinct values for h, providing a method of testing our
      hypotheses. The generality of our model suggests implications for vascular
      morphology, in particular, differing number and shapes of arterial and venous
      trees.

PMID- 23005750
TI  - Number of common sites visited by N random walkers.
AB  - We compute analytically the mean number of common sites, W(N)(t), visited by N
      independent random walkers each of length t and all starting at the origin at t =
      0 in d dimensions. We show that in the (N-d) plane, there are three distinct
      regimes for the asymptotic large-t growth of W(N)(t). These three regimes are
      separated by two critical lines d = 2 and d = d(c)(N) = 2N/(N-1) in the (N-d)
      plane. For d<2, W(N) (t) ~ t(d/2) for large t (the N dependence is only in the
      prefactor). For 2 < d < d(c)(N), W(N)(t) ~ t(nu) where the exponent nu = N-d(N
      1)/2 varies with N and d. For d > d(c)(N), W(N)(t) -> const as t -> infinity.
      Exactly at the critical dimensions there are logarithmic corrections: for d=2, we
      get W(N)(t) ~ t/[ln t](N), while for d = d(c)(N), W(N)(t) ~ ln t for large t. Our
      analytical predictions are verified in numerical simulations.

PMID- 23005751
TI  - Levy flights and multifractality in quantum critical diffusion and in classical
      random walks on fractals.
AB  - We employ the method of virial expansion to compute the retarded density
      correlation function (generalized diffusion propagator) in the critical random
      matrix ensemble in the limit of strong multifractality. We find that the long
      range nature of the Hamiltonian is a common root of both multifractality and Levy
      flights, which show up in the power-law intermediate- and long-distance
      behaviors, respectively, of the density correlation function. We review certain
      models of classical random walks on fractals and show the similarity of the
      density correlation function in them to that for the quantum problem described by
      the random critical long-range Hamiltonians.

PMID- 23005752
TI  - Transport coefficients and the spinodal of a fluid.
AB  - Based on the results of computer simulation of transport coefficients in a
      Lennard-Jones fluid, it has been shown that in (p,T) coordinates, lines of
      constant values of coefficients of self-diffusion D and excess shear viscosity
      Deltaeta extended into the region of superheated liquid and supersaturated vapor
      have an envelope. Each of the ensembles of such lines is divided into two parts
      by a critical isoline, where the conditions phi = phic = const (phi = D,Deltaeta)
      are fulfilled. One part of this ensemble has as an envelope the branch of the
      spinodal that refers to superheated liquid; the other part has the branch of the
      spinodal of supersaturated vapor. The critical point of liquid-vapor equilibrium
      is the cusp of the spinodal, at which the critical isolines have a common tangent
      line with the spinodal and the binodal. Thus, at the approach to the spinodal,
      the relations (?D/?p)(T) -> infinity and (?Deltaeta/?p)(T) -> infinity hold.

PMID- 23005753
TI  - Local viscosity of a fluid confined in a narrow pore.
AB  - In this paper, molecular dynamics simulations of a simple Lennard-Jones fluid
      confined in narrow slit pores and undergoing shear have been performed. The aim
      is to investigate the effects of density inhomogeneities at the fluid-solid
      interfaces on the shear viscosity profiles. It has been found that the local
      viscosity was varying strongly with the distance from the solid walls for both
      dilute and dense fluid states with oscillations correlated to the density ones.
      To describe the computed viscosity profiles, we propose a scheme that uses the
      local average density model, combined with an adequate weight function, for the
      configurational viscosity and a semiempirical model for the translational
      viscosity. It is shown that the proposed approach is able to provide viscosity
      profiles in good agreement with those coming from simulations for different pore
      widths and for different fluid states (dilute to dense).

PMID- 23005754
TI  - Dynamics of the wet granular Leidenfrost phenomenon.
AB  - By event-driven molecular dynamics simulations, we study the Leidenfrost effect
      for wet granular matter driven from below. In marked contrast to all earlier
      studies on other fluids, the dense plug hovering on the hot gas cushion undergoes
      an undamped oscillation. The location of the Hopf bifurcation leading to this
      oscillation is strongly dependent on the inelasticity of the grain impacts. The
      vertical separation into a gas phase with a condensed plug hovering above it is
      particularly pronounced due to the cohesiveness of the granulate. For
      sufficiently large system sizes, the Rayleigh-Taylor instability terminates the
      oscillatory state at late times.

PMID- 23005755
TI  - Force propagation in isostatic granular packs.
AB  - We investigate how forces spread through frictionless granular packs at the
      jamming transition. Previous work has indicated that such packs are isostatic,
      and thus obey a null stress law which, independent of the packing history, causes
      rays of stress to propagate away from a point force at oblique angles. Prior
      verifications of the null stress law have used a sequential packing method which
      yields packs with anisotropic packing histories. We create packs without this
      anisotropy, and then later break the symmetry by adding a boundary. Our isotropic
      packs are very sensitive, and their responses to point forces diverge wildly,
      indicating that they cannot be described by any continuum stress model. We
      stabilize the packs by supplying an additional boundary, which makes the response
      much more regular. The response of the stabilized packs resembles what one would
      expect in a hyperstatic pack, despite the isostatic bulk. The expected stress
      rays characteristic of null stress behavior are not present. This suggests that
      isostatic packs do not need to obey a null stress condition. We argue that the
      rays may arise instead from more simple geometric considerations, such as
      preferred contact angles between beads.

PMID- 23005756
TI  - Mechanisms for agglomeration and deagglomeration following oblique collisions of
      wet particles.
AB  - Previous studies on wetted, particle-particle collisions have been limited to
      head-on collisions, but in many-particle flows, collisions are inherently
      oblique. In this work, we explore such oblique collisions experimentally and
      theoretically. Whereas in normal collisions particles rebound only due to solid
      deformation, we observe in oblique collisions a new outcome where the particles
      initially form a rotating doublet and then deagglomerate at a later time due to
      so-called centrifugal forces. Surprisingly, we discover the essential role of
      capillary forces in oblique collisions even when the capillary number (viscous
      over capillary forces) is high. This recognition leads to the introduction of a
      dimensionless number, the centrifugal number (centrifugal over capillary forces),
      which together with the previously established Stokes number characterizes the
      regime map of outcomes. Unexpectedly, we observe a normal restitution coefficient
      greater than unity at large impact angles, the mechanism for which may also be
      observed in other agglomerating systems.

PMID- 23005757
TI  - Interaction dynamics of two colloids in a single optical potential.
AB  - The interaction of two diffusing particles is strongly influenced by their
      hydrodynamic coupling. At a tracking rate of 10 kHz we are able to measure the 3D
      trajectories of two colloidal spheres in a single harmonic potential, which was
      generated by scanning line optical tweezers. This common potential enables
      tilting, rotational, and translational dynamics of the spheres, which we analyzed
      via the spheres position cross-correlations C(tau) over a time range of 10(-4)-2
      s. We found that the dynamic interaction of the colloids is controlled by short
      range surface forces F(s), which are attractive in one direction and repulsive in
      the other two directions. This unexpected behavior is supported by a theoretical
      model using two Langevin equations, which decouple for linear F(s), allowing a
      description with autocorrelation functions for collective and relative motions.
      We further demonstrate that variations in salt concentration and reaction volumes
      significantly influence C(tau) and the mean contact times between the particles,
      which may offer new insights into biological particle interaction.

PMID- 23005758
TI  - Coarsening of a two-dimensional foam on a dome.
AB  - In this paper we report on bubble growth rates and on the statistics of bubble
      topology for the coarsening of a dry foam contained in the narrow gap between two
      hemispheres. By contrast with coarsening in flat space, where six-sided bubbles
      neither grow nor shrink, we observe that six-sided bubbles grow with time at a
      rate that depends on their size. This result agrees with the modification to von
      Neumann's law predicted by J. E. Avron and D. Levine [Phys. Rev. Lett. 69, 208
      (1992)]. For bubbles with a different number of sides, except possibly seven,
      there is too much noise in the growth rate data to demonstrate a difference with
      coarsening in flat space. In terms of the statistics of bubble topology, we find
      fewer three-, four-, and five-sided bubbles, and more bubbles with six or more
      sides, in comparison with the stationary distribution for coarsening in flat
      space. We also find good general agreement with the Aboav-Weaire law for the
      average number of sides of the neighbors of an n-sided bubble.

PMID- 23005759
TI  - First-principles constitutive equation for suspension rheology.
AB  - We provide a detailed derivation of a recently developed first-principles
      approach to calculating averages in systems of interacting, spherical Brownian
      particles under time-dependent flow. Although we restrict ourselves to flows
      which are both homogeneous and incompressible, the time dependence and geometry
      (e.g., shear and extension) are arbitrary. The approximations formulated within
      mode-coupling theory are particularly suited to dense colloidal suspensions and
      capture the slow relaxation arising from particle interactions and the resulting
      glass transition to an amorphous solid. The delicate interplay between slow
      structural relaxation and time-dependent external flow in colloidal suspensions
      thus may be studied within a fully tensorial theory.

PMID- 23005760
TI  - Description of hard-sphere crystals and crystal-fluid interfaces: a comparison
      between density functional approaches and a phase-field crystal model.
AB  - In materials science the phase-field crystal approach has become popular to model
      crystallization processes. Phase-field crystal models are in essence Landau
      Ginzburg-type models, which should be derivable from the underlying microscopic
      description of the system in question. We present a study on classical density
      functional theory in three stages of approximation leading to a specific phase
      field crystal model, and we discuss the limits of applicability of the models
      that result from these approximations. As a test system we have chosen the three
      dimensional suspension of monodisperse hard spheres. The levels of density
      functional theory that we discuss are fundamental measure theory, a second-order
      Taylor expansion thereof, and a minimal phase-field crystal model. We have
      computed coexistence densities, vacancy concentrations in the crystalline phase,
      interfacial tensions, and interfacial order parameter profiles, and we compare
      these quantities to simulation results. We also suggest a procedure to fit the
      free parameters of the phase-field crystal model. Thereby it turns out that the
      order parameter of the phase-field crystal model is more consistent with a
      smeared density field (shifted and rescaled) than with the shifted and rescaled
      density itself. In brief, we conclude that fundamental measure theory is very
      accurate and can serve as a benchmark for the other theories. Taylor expansion
      strongly affects free energies, surface tensions, and vacancy concentrations.
      Furthermore it is phenomenologically misleading to interpret the phase-field
      crystal model as stemming directly from Taylor-expanded density functional
      theory.

PMID- 23005761
TI  - Structural and elastic properties of a confined two-dimensional colloidal solid:
      a molecular dynamics study.
AB  - We implement molecular dynamics simulations in canonical ensemble to study the
      effect of confinement on a two-dimensional crystal of point particles interacting
      with an inverse power law potential proportional to r^{-12} in a narrow channel.
      This system can describe colloidal particles at the air-water interface. It is
      shown that the system characteristics depend sensitively on the boundary
      conditions at the two walls providing the confinement. The walls exert
      perpendicular forces on their adjacent particles. The potential between walls and
      particles varies as the inverse power of ten. Structural quantities such as
      density profile, structure factor, and orientational order parameter are
      computed. It is shown that orientational order persists near the walls even at
      temperatures where the system in the bulk is in fluid state. The dependence of
      elastic constants, stress tensor elements, shear, and bulk moduli on density as
      well as the channel width is discussed. Moreover, the effect of channel
      incommensurability with the triangular lattice structure is discussed. It is
      shown that incommensurability notably affects the system properties. We compare
      our findings to those obtained by Monte Carlo simulations in Rici et al. [Phys.
      Rev. E 75, 011405 (2007)] and to the case with the periodic boundary condition
      along the channel width.

PMID- 23005762
TI  - Hysteresis and return-point memory in colloidal artificial spin ice systems.
AB  - Using computer simulations, we investigate hysteresis loops and return-point
      memory for artificial square and kagome spin ice systems by cycling an applied
      bias force and comparing microscopic effective spin configurations throughout the
      hysteresis cycle. Return-point memory loss is caused by motion of individual
      defects in kagome ice or of grain boundaries in square ice. In successive cycles,
      return-point memory is recovered rapidly in kagome ice. Memory is recovered more
      gradually in square ice due to the extended nature of the grain boundaries.
      Increasing the amount of quenched disorder increases the defect density but also
      enhances the return-point memory since the defects become trapped more easily.

PMID- 23005763
TI  - Glass transition in thin supported polystyrene films probed by temperature
      modulated ellipsometry in vacuum.
AB  - Glass transition in thin (1-200 nm thick) spin-cast polystyrene films on silicon
      surfaces is probed by ellipsometry in a controlled vacuum environment. A
      temperature-modulated modification of the method is used alongside a traditional
      linear temperature scan. A clear glass transition is detected in films with
      thicknesses as low as 1-2 nm. The glass transition temperature (T(g)) shows no
      substantial dependence on thickness for coatings greater than 20 nm. Thinner
      films demonstrate moderate T(g) depression achieving 18 K for thicknesses 4-7 nm.
      Less than 4 nm thick samples are excluded from the T(g) comparison due to
      significant thickness nonuniformity (surface roughness). The transition in 10-20
      nm thick films demonstrates excessive broadening. For some samples, the broadened
      transition is clearly resolved into two separate transitions. The thickness
      dependence of the glass transition can be well described by a simple 2-layer
      model. It is also shown that T(g) depression in 5 nm thick films is not sensitive
      to a wide range of experimental factors including molecular weight
      characteristics of the polymer, specifications of solvent used for spin casting,
      substrate composition, and pretreatment of the substrate surface.

PMID- 23005764
TI  - Mode-coupling theory of the glass transition for confined fluids.
AB  - We present a detailed derivation of a microscopic theory for the glass transition
      of a liquid enclosed between two parallel walls relying on a mode-coupling
      approximation. This geometry lacks translational invariance perpendicular to the
      walls, which implies that the density profile and the density-density correlation
      function depends explicitly on the distances to the walls. We discuss the
      residual symmetry properties in slab geometry and introduce a symmetry adapted
      complete set of two-point correlation functions. Since the currents naturally
      split into components parallel and perpendicular to the walls the mathematical
      structure of the theory differs from the established mode-coupling equations in
      bulk. We prove that the equations for the nonergodicity parameters still display
      a covariance property similar to bulk liquids.

PMID- 23005765
TI  - Macroscale description of electrokinetic flows at large zeta potentials:
      nonlinear surface conduction.
AB  - For highly charged dielectric surfaces, the asymptotic structure underlying
      electrokinetic phenomena in the thin-double-layer limit reshuffles. The large
      counterion concentration near the surface, associated with the Boltzmann
      distribution in the diffuse layer, supports appreciable tangential fluxes
      appearing as effective surface currents in a macroscale description. Their
      inevitable nonuniformity gives rise in turn to comparable transverse currents,
      which, for logarithmically large zeta potentials, modify the electrokinetic
      transport in the electroneutral bulk. To date, this mechanism has been studied
      only using a weak-field linearization. We present here a generic thin-double
      layer analysis of the electrokinetic transport about highly charged dielectric
      solids, which is not restricted to weak fields. We identify the counterion
      concentration amplification with the emergence of an internal boundary layer-
      within the diffuse part of the double layer--characterized by distinct scaling of
      ionic concentrations and electric field. In this multiscale description, surface
      conduction is conveniently localized within the internal layer. Our systematic
      scheme thus avoids the cumbersome procedure of retaining small asymptotic terms
      which change their magnitude at large zeta potentials. The electrokinetic
      transport predicted by the resulting macroscale model is inherently accompanied
      by bulk concentration polarization, which in turn results in nonlinear bulk
      transport. A novel fundamental subtlety associated with this intrinsic feature,
      overlooked in the weak-field approximation, has to do with the ambiguity of the
      "particle zeta potential" concept: In general, even uniformly charged surfaces
      are characterized by a nonuniform zeta-potential distribution. This impairs the
      need for a careful identification of the dimensionless number representing the
      transition to large zeta potentials.

PMID- 23005766
TI  - Curvature-driven effective attraction in multicomponent membranes.
AB  - We study closed liquid membranes that segregate into three phases due to
      differences in the chemical and physical properties of its components. The shape
      and in-plane membrane arrangement of the phases are coupled through phase
      specific bending energies and line tensions. We use simulated annealing Monte
      Carlo simulations to find low-energy structures, allowing both phase arrangement
      and membrane shape to relax. The three-phase system is the simplest one in which
      there are multiple interface pairs, allowing us to analyze interfacial
      preferences and pairwise distinct line tensions. We observe the system's
      preference for interface pairs that maximize differences in spontaneous
      curvature. From a pattern selection perspective, this acts as an effective
      attraction between phases of most disparate spontaneous curvature. We show that
      this effective attraction is robust enough to persist even when the interface
      between these phases is the most penalized by line tension. This effect is driven
      by geometry and not by any explicit component-component interaction.

PMID- 23005767
TI  - Nonequilibrium static diverging length scales on approaching a prototypical model
      glassy state.
AB  - Maximally random jammed states of hard spheres are prototypical glasses. We study
      the small wavenumber k behavior of the structure factor S(k) of overcompressed
      million-sphere packings as a function of density up to the jammed state. We find
      both a precursor to the glassy jammed state evident long before the jamming
      density is reached and two associated growing length scales, one extracted from
      the volume integral of the direct correlation function c(r) and the other from
      the small-k behavior of the structure factor S(k), that can diverge at the
      "critical" jammed state. We also define a nonequilibrium index X and use it to
      demonstrate that the packings studied are intrinsically nonequilibrium in nature
      well before the critical state is reached. The extension of the results reported
      in the present work to supercooled atomic-liquid models in which the atoms
      interact with both repulsive and attractive forces is also discussed.

PMID- 23005768
TI  - Enhanced translational diffusion of confined water under electric field.
AB  - High resolution quasielastic neutron scattering measurements have been used to
      study the effects of applied electric field on the dynamics of water molecules
      confined in the pores of folded silica sheet material FSM-12 with an average pore
      diameter (apd) of 16 A. In the absence of field, there is a significant slowing
      down of the water molecule diffusion as the temperature is lowered, in agreement
      with previous observations. The application of a moderate electric field of 2.5
      kV/mm remarkably enhances the translational diffusion of water molecules. We
      interpret this as being due to a disruption of the hydrogen bonding by the
      electric field. This new observation suggests that existing theories valid at
      large electric field strengths may have to be corrected at moderate fields.

PMID- 23005769
TI  - Orientational order in cylinder-forming block copolymer thin films.
AB  - Shear can impart a high degree of orientational order to supported block
      copolymer thin films containing one or more layers of cylindrical microdomains,
      leading to a striped pattern with a period of tens of nanometers extending over
      macroscopic (centimeter-squared) areas. Though the as-deposited films have a
      polygrain structure, after shearing at sufficiently high stresses the only
      defects which remain are isolated dislocations, and the orientational order can
      be quite high (nematic or twofold orientational order parameter >0.99, as
      measured by tapping-mode atomic force microscopy). The effect of isolated
      dislocations on orientational order is adequately captured by an isotropic
      elastic continuum model of the structure surrounding the dislocation, producing a
      linear decrease of order parameter with dislocation density. Even at zero
      dislocation density, however, the order parameter does not quite reach unity, due
      to small-amplitude undulations of the cylinders about their axes which persist in
      the transverse direction over several cylinder periods.

PMID- 23005770
TI  - Translation-rotation decoupling and nonexponentiality in room temperature ionic
      liquids.
AB  - Using a combination of light scattering techniques and broadband dielectric
      spectroscopy, we have measured the temperature dependence of structural
      relaxation time and self diffusion in three imidazolium-based room temperature
      ionic liquids: [bmim][NTf(2)], [bmim][PF(6)], and [bmim][TFA]. A detailed
      analysis of the results demonstrates that self diffusion decouples from
      structural relaxation in these systems as the temperature is decreased toward
      T(g). The degree to which the dynamics are decoupled, however, is shown to be
      surprisingly weak when compared to other supercooled liquids of similar
      fragility. In addition to the weak decoupling, we demonstrate that the
      temperature dependence of the structural relaxation time in all three liquids can
      be well described by a single Vogel-Fulcher-Tamann function over 13 decades in
      time from 10(-11) s up to 10(2) s. Furthermore, the stretching of the structural
      relaxation is shown to be temperature independent over the same range of time
      scales, i.e., time temperature superposition is valid for these ionic liquids
      from far above the melting point down to the glass transition temperature. We
      suggest that these phenomena are interconnected and all result from the same
      underlying mechanism--strong and directional intermolecular interactions.

PMID- 23005771
TI  - Effects of mixed discrete surface charges on the electrical double layer.
AB  - Adsorption of surface coions and charge reversal are induced at the electrical
      double layer of a wall charged with positive and negative surface sites next to
      an electrolyte solution. While for the considered surface charge density these
      effects are found over a wide range of conditions, they are not observed for the
      typically employed surface models in equivalent conditions. Important
      consequences in electrophoresis experiments for different colloids with equal
      effective surface charge density are foreseen. This study is carried out by means
      of molecular dynamics simulations.

PMID- 23005772
TI  - Thermal effects of the substrate on water droplet evaporation.
AB  - We experimentally investigate the behavior of a pinned water droplet evaporating
      into air. The influence of the substrate temperature and substrate thermal
      properties on the evaporation process are studied in both hydrophilic and
      hydrophobic conditions. Our objective is to understand the effect of thermal
      mechanisms on the droplet evaporation process. The experimental results are
      compared with the quasisteady, diffusion-driven evaporation model, which is
      implemented under the influence of the temperature; the model assumes the
      isothermia of the droplet at the substrate temperature. The results highlight a
      favorable correlation between the model and the experimental data at ambient
      temperatures for most situations considered here. The model works to
      qualitatively describe the influence of the substrate temperature on the
      evaporation process. However, with an increase in the substrate temperature, the
      role of the thermal-linked mechanisms becomes increasingly important; this
      experiment highlights the need for more accurate models to account for the
      buoyant convection in vapor transport and the evaporative cooling and heat
      conduction between the droplet and the substrate. Finally, the experimental data
      reveal the modification of contact angle evolution as the temperature increases
      and the crucial role played by the nature of the substrate in the evaporation of
      a sessile droplet. The influence of the substrate thermal properties on the
      global evaporation rate is explained by the parallel thermal effusivity of the
      liquid and solid phases.

PMID- 23005773
TI  - Solidification in syntectic and monotectic systems.
AB  - We present theoretical studies of syntectic and monotectic solidification
      scenarios. Steady-state solidification along the liquid-liquid interface in a
      syntectic system is considered by means of a boundary-integral technique
      developed previously. We study the case of small asymmetry of the pattern and
      extract from the results the scaling relations in terms of the undercooling and
      the asymmetry parameter. We also investigate monotectic solidification using the
      phase-field method. We present two kinds of two-phase fingers, with the solid
      phase being either the exterior phase or the interior phase, and the pattern
      corresponding to the growth along the solid-liquid interface. We finally analyze
      the asymptotic shape of these new morphologies far behind their tip.

PMID- 23005774
TI  - Influence of nanoconfinement on the nematic behavior of liquid crystals.
AB  - We explore the nematic ordering of the rodlike liquid crystals 5CB and 6CB,
      embedded into parallel-aligned nanochannels in mesoporous silicon and silica
      membranes as a function of mean channel radius (4.7 <= R <= .3 nm), and, thus,
      geometrical confinement strength, by optical birefringence measurements in the
      infrared region. The orientational order inside the nanochannels results in an
      excess birefringence, which is proportional to the nematic order parameter. It
      evolves continuously on cooling with a precursor behavior, typical of a
      paranematic state at high temperatures. These observations are compared with the
      bulk behavior and analyzed within a phenomenological model. Such an approach
      indicates that the strength of the nematic ordering fields sigma is beyond a
      critical threshold sigma(c) = 1/2 that separates discontinuous from continuous
      paranematic-to-nematic behavior. In agreement with the predictions of the
      phenomenological approach, a linear dependency of sigma on the inverse channel
      radius is found and we can infer therefrom the critical channel radii, R(c)
      separating continuous from discontinuous paranematic-to-isotropic behavior, for
      5CB (12.1 nm) and 6CB (14.0 nm). Our analysis suggests that the tangential
      anchoring at the channel walls is of similar strength in mesoporous silicon and
      mesoporous silica membranes. A comparison with the bulk phase behavior reveals
      that the nematic order in nanoconfinement is significantly affected by channel
      wall roughness, leading to a reduction of the effective nematic ordering.

PMID- 23005775
TI  - Temporal evolution and alternation of mechanisms of electric-field-induced
      patterns at ultralow-frequency driving.
AB  - The temporal evolution of patterns within the driving period of the ac voltage
      was studied in the 10-mHz-250-Hz frequency range. It was shown that the
      stationary electroconvection pattern of the conductive regime transforms into a
      flashing one at ultralow frequencies, existing only in narrow time windows within
      the period. Furthermore a transition between electroconvection and flexoelectric
      domains was detected which is repeating in each half period. The two patterns are
      well separated in time and in Fourier space. Simultaneous current measurements
      uncovered that the electric properties of the polyimide orienting layers
      influence the redistribution of the applied voltage. The experimental findings
      are in good qualitative agreement with the theoretical predictions based on an
      extended standard model including flexoelectricity.

PMID- 23005776
TI  - Optical generation of crystalline, quasicrystalline, and arbitrary arrays of
      torons in confined cholesteric liquid crystals for patterning of optical vortices
      in laser beams.
AB  - Condensed matter systems with topological defects in the ground states range from
      the Abrikosov phases in superconductors, to various blue phases and twist grain
      boundary phases in liquid crystals, and to phases of skyrmion lattices in chiral
      ferromagnets and Bose-Einstein condensates. In nematic and chiral nematic liquid
      crystals, which are true fluids with long-range orientational ordering of
      constituent molecules, point and line defects spontaneously occur as a result of
      symmetry-breaking phase transitions or due to flow, but they are unstable, hard
      to control, and typically annihilate with time. Here we describe the optical
      generation of two-dimensional crystalline, quasicrystalline, and arbitrary
      ensembles of particlelike structures manifesting both skyrmionlike and Hopf
      fibration features--dubbed "torons"--composed of looped double twist cylinders
      and point defects embedded in a uniform director field. In these two-dimensional
      lattices, we then introduce various dislocations, defects in positional ordering
      of the torons. We show that the periodic defect lattices with and without
      dislocation are light- and voltage-tunable reconfigurable two-dimensional
      diffraction gratings and can be used to generate various controlled phase
      singularities in the diffracted laser beams. The results of computer simulations
      of optical images, diffraction patterns, and phase distributions with optical
      vortices are in a good agreement with the corresponding experimental findings.

PMID- 23005777
TI  - Immersion energy and polymer-mediated depletion interactions between nanocolloids
      as studied by analytic self-consistent field theory.
AB  - By applying the Edwards self-consistent field theory, we calculate the polymer
      density and free energy excesses caused by the presence of nanocolloids in the
      excluded volume polymer system. Using the obtained results, we have calculated
      the depletion potential U as a function of the separation between colloids,
      colloid radius, polymer volume fraction, and polymer gyration radius. Upon
      analyzing the obtained results against the known exact asymptotic small
      separation limit and scaling relations, we propose an approximate expression for
      U that builds upon our exact result. This expression is shown to give excellent
      agreement with Monte Carlo simulations. Reliability of the derived analytical
      expression for the depletion potential and its relation to the previous
      theoretical and simulation work are thoroughly discussed.

PMID- 23005778
TI  - Mechanisms of crazing in glassy polymers revealed by molecular dynamics
      simulations.
AB  - Mechanisms leading to initiation of crazing type failure in a glassy polymer are
      not clearly understood. This is mainly due to the difficulty in characterizing
      the stress state and polymer configuration sufficiently locally at the craze
      initiation site. Using molecular dynamics simulations, we have now been able to
      access this information and have shown that the local heterogeneous deformation
      leads to craze initiation in glassy polymers. We found that zones of high plastic
      activity are constrained by their neighborhood and become unstable, initiating
      crazing from these sites. Furthermore, based on the constant flow stresses
      observed in the unstable zones, we conclude that microcavitation is the essential
      local deformation mode to trigger crazing in glassy polymers. Our results
      demonstrate the basic difference in the local deformation mode as well as the
      conditions that lead to either shear-yielding or crazing type failures in glassy
      polymers. We anticipate our paper to help in devising a new criterion for craze
      initiation that not only considers the stress state, but also considers local
      deformation heterogeneities that form the necessary condition for crazing in
      glassy polymers.

PMID- 23005779
TI  - Salt dependence of the radius of gyration and flexibility of single-stranded DNA
      in solution probed by small-angle x-ray scattering.
AB  - Short single-stranded nucleic acids are ubiquitous in biological processes;
      understanding their physical properties provides insights to nucleic acid folding
      and dynamics. We used small-angle x-ray scattering to study 8-100 residue
      homopolymeric single-stranded DNAs in solution, without external forces or
      labeling probes. Poly-T's structural ensemble changes with increasing ionic
      strength in a manner consistent with a polyelectrolyte persistence length theory
      that accounts for molecular flexibility. For any number of residues, poly-A is
      consistently more elongated than poly-T, likely due to the tendency of A residues
      to form stronger base-stacking interactions than T residues.

PMID- 23005780
TI  - Intrinsic fluctuations lead to broad range of transduced forces in tethered-bead
      single-molecule experiments.
AB  - We build a theoretical platform for predicting the behavior of tethered-bead
      single-molecule experiments, accounting for bead translational and rotational
      fluctuations, the specific type of experimental setup, and the detailed
      application of tension to the tether molecule. Within this framework, the
      external force applied to the bead is distinguished from the instantaneous force
      transduced to the tether molecule, resulting in a distinction between the
      observable response of the bead and the underlying force fluctuations felt by the
      tether that directly affect the biomolecular processes being studied. Our
      theoretical model indicates that the spread of the distribution of tether forces
      increases with applied external force, resulting in substantial deviations
      between the external and tether forces. We find that the impact of rotational and
      translational fluctuations of the bead motion is larger in magnetic tweezers than
      optical tweezers. However, this distinction diminishes at large external forces,
      and our asymptotic expressions offer a simple route for experimental analyses.
      Overall, our theory demonstrates that fluctuations in the tether molecule due to
      bead rotation and translation lead to a broad range of tether forces.

PMID- 23005781
TI  - Breathing, bubbling, and bending: DNA flexibility from multimicrosecond
      simulations.
AB  - Bending of the seemingly stiff DNA double helix is a fundamental physical process
      for any living organism. Specialized proteins recognize DNA inducing and
      stabilizing sharp curvatures of the double helix. However, experimental evidence
      suggests a high protein-independent flexibility of DNA. On the basis of coarse
      grained simulations, we propose that DNA experiences thermally induced kinks
      associated with the spontaneous formation of internal bubbles. Comparison of the
      protein-induced DNA curvature calculated from the Protein Data Bank with that
      sampled by our simulations suggests that thermally induced distortions can
      account for ~80% of the DNA curvature present in experimentally solved
      structures.

PMID- 23005782
TI  - Correlation between protein secondary structure, backbone bond angles, and side
      chain orientations.
AB  - We investigate the fine structure of the sp3 hybridized covalent bond geometry
      that governs the tetrahedral architecture around the central C(alpha) carbon of a
      protein backbone, and for this we develop new visualization techniques to analyze
      high-resolution x-ray structures in the Protein Data Bank. We observe that there
      is a correlation between the deformations of the ideal tetrahedral symmetry and
      the local secondary structure of the protein. We propose a universal coarse
      grained energy function to describe the ensuing side-chain geometry in terms of
      the C(beta) carbon orientations. The energy function can model the side-chain
      geometry with a subatomic precision. As an example we construct the C(alpha)
      C(beta) structure of HP35 chicken villin headpiece. We obtain a configuration
      that deviates less than 0.4 A in root-mean-square distance from the experimental
      x-ray structure.

PMID- 23005784
TI  - NMR-based diffusion pore imaging.
AB  - Nuclear magnetic resonance (NMR) diffusion experiments offer a unique opportunity
      to study boundaries restricting the diffusion process. In a recent Letter [Phys.
      Rev. Lett. 107, 048102 (2011)], we introduced the idea and concept that such
      diffusion experiments can be interpreted as NMR imaging experiments.
      Consequently, images of closed pores, in which the spins diffuse, can be
      acquired. In the work presented here, an in-depth description of the diffusion
      pore imaging technique is provided. Image artifacts due to gradient profiles of
      finite duration, field inhomogeneities, and surface relaxation are considered.
      Gradients of finite duration lead to image blurring and edge enhancement
      artifacts. Field inhomogeneities have benign effects on diffusion pore images,
      and surface relaxation can lead to a shrinkage and shift of the pore image. The
      relation between boundary structure and the imaginary part of the diffusion
      weighted signal is analyzed, and it is shown that information on pore coherence
      can be obtained without the need to measure the phase of the diffusion weighted
      signal. Moreover, it is shown that quite arbitrary gradient profiles can be used
      for diffusion pore imaging. The matrices required for numerical calculations are
      stated and provided as supplemental material.

PMID- 23005783
TI  - Advection, diffusion, and delivery over a network.
AB  - Many biological, geophysical, and technological systems involve the transport of
      a resource over a network. In this paper, we present an efficient method for
      calculating the exact quantity of the resource in each part of an arbitrary
      network, where the resource is lost or delivered out of the network at a given
      rate, while being subject to advection and diffusion. The key conceptual step is
      to partition the resource into material that does or does not reach a node over a
      given time step. As an example application, we consider resource allocation
      within fungal networks, and analyze the spatial distribution of the resource that
      emerges as such networks grow over time. Fungal growth involves the expansion of
      fluid filled vessels, and such growth necessarily involves the movement of fluid.
      We develop a model of delivery in growing fungal networks, and find good
      empirical agreement between our model and experimental data gathered using radio
      labeled tracers. Our results lead us to suggest that in foraging fungi, growth
      induced mass flow is sufficient to account for long-distance transport, if the
      system is well insulated. We conclude that active transport mechanisms may only
      be required at the very end of the transport pathway, near the growing tips.

PMID- 23005785
TI  - Single-molecule study of molecular mobility in the cytoplasm of Escherichia coli.
AB  - The cytoplasm of bacterial cells is filled with individual molecules and
      molecular complexes that rely on diffusion to bring them together for
      interaction. The mobility of molecules in the cytoplasm has been characterized by
      several techniques mainly using fluorescent probes and ensemble methods. In order
      to probe the microenvrionment inside the cytoplasm as viewed by an individual
      molecule, we have studied single green fluorescent proteins (GFPs) diffusing in
      the cytoplasm of Escherichia coli cells at observation at rates ranging from 60
      to 1000 Hz. Over long times the diffusion shows confinement due to the geometry
      of the cells themselves. A simulation in model cells using the actual
      distribution of cell sizes found in the experiments describes accurately the
      experimental results as well as reveals a short time diffusion coefficient that
      agrees well with that determined by ensemble methods. Higher short time diffusion
      coefficients can be obtained by filling the simulated cell with small spheres
      modeling cytoplasmic molecules and, depending on the density of particles
      included in the modeled cytoplasm, can approach the diffusion coefficient of GFPs
      found in water. Thus, single-molecule tracking combined with analysis using
      simple simulation of Brownian motion is able to reveal the main contributors to
      the GFP mobility in the cytoplasm of E. coli.

PMID- 23005786
TI  - Mesoscopic model for free-energy-landscape analysis of DNA sequences.
AB  - A mesoscopic model which allows us to identify and quantify the strength of
      binding sites in DNA sequences is proposed. The model is based on the Peyrard
      Bishop-Dauxois model for the DNA chain coupled to a Brownian particle which
      explores the sequence interacting more importantly with open base pairs of the
      DNA chain. We apply the model to promoter sequences of different organisms. The
      free energy landscape obtained for these promoters shows a complex structure that
      is strongly connected to their biological behavior. The analysis method used is
      able to quantify free energy differences of sites within genome sequences.

PMID- 23005787
TI  - How to enhance the dynamic range of excitatory-inhibitory excitable networks.
AB  - We investigate the collective dynamics of excitatory-inhibitory excitable
      networks in response to external stimuli. How to enhance the dynamic range, which
      represents the ability of networks to encode external stimuli, is crucial to many
      applications. We regard the system as a two-layer network (E layer and I layer)
      and explore the criticality and dynamic range on diverse networks. Interestingly,
      we find that phase transition occurs when the dominant eigenvalue of the E
      layer's weighted adjacency matrix is exactly 1, which is only determined by the
      topology of the E layer. Meanwhile, it is shown that the dynamic range is
      maximized at a critical state. Based on theoretical analysis, we propose an
      inhibitory factor for each excitatory node. We suggest that if nodes with high
      inhibitory factors are cut out from the I layer, the dynamic range could be
      further enhanced. However, because of the sparseness of networks and passive
      function of inhibitory nodes, the improvement is relatively small compared to the
      original dynamic range. Even so, this provides a strategy to enhance the dynamic
      range.

PMID- 23005788
TI  - Biopolymer hairpin loops sustained by polarons.
AB  - We show that polarons can sustain looplike configurations in flexible biopolymers
      and that the size of the loops depend on both the flexural rigidity of the
      polymer and the electron-phonon coupling constant. In particular we show that for
      single stranded DNA (ssDNA) and polyacetylene such loops can have as few as seven
      monomers. We also show that these configurations are very stable under thermal
      fluctuations and so could facilitate the formation of hairpin loops of ssDNA.

PMID- 23005789
TI  - Discriminating the effects of spatial extent and population size in cyclic
      competition among species.
AB  - We introduce a population model for species under cyclic competition. This model
      allows individuals to coexist and interact on single cells while migration takes
      place between adjacent cells. In contrast to the model introduced by Reichenbach,
      Mobilia, and Frey [Reichenbach, Mobilia, and Frey, Nature (London) 448, 1046
      (2007)], we find that the emergence of spirals results in an ambiguous behavior
      regarding the stability of coexistence. The typical time until extinction
      exhibits, however, a qualitatively opposite dependence on the newly introduced
      nonunit carrying capacity in the spiraling and the nonspiraling regimes. This
      allows us to determine a critical mobility that marks the onset of this spiraling
      state sharply. In contrast, we demonstrate that the conventional finite size
      stability analysis with respect to spatial size is of limited use for identifying
      the onset of the spiraling regime.

PMID- 23005790
TI  - High-resolution detection of Brownian motion for quantitative optical tweezers
      experiments.
AB  - We have developed an in situ method to calibrate optical tweezers experiments and
      simultaneously measure the size of the trapped particle or the viscosity of the
      surrounding fluid. The positional fluctuations of the trapped particle are
      recorded with a high-bandwidth photodetector. We compute the mean-square
      displacement, as well as the velocity autocorrelation function of the sphere, and
      compare it to the theory of Brownian motion including hydrodynamic memory
      effects. A careful measurement and analysis of the time scales characterizing the
      dynamics of the harmonically bound sphere fluctuating in a viscous medium
      directly yields all relevant parameters. Finally, we test the method for
      different optical trap strengths, with different bead sizes and in different
      fluids, and we find excellent agreement with the values provided by the
      manufacturers. The proposed approach overcomes the most commonly encountered
      limitations in precision when analyzing the power spectrum of position
      fluctuations in the region around the corner frequency. These low frequencies are
      usually prone to errors due to drift, limitations in the detection, and trap
      linearity as well as short acquisition times resulting in poor statistics.
      Furthermore, the strategy can be generalized to Brownian motion in more complex
      environments, provided the adequate theories are available.

PMID- 23005791
TI  - Feed-forward loops and diamond motifs lead to tunable transmission of information
      in the frequency domain.
AB  - Using a Gaussian model, we study the transmission of time-varying biochemical
      signals through feed-forward motifs and diamond motifs. To this end, we compute
      the frequency dependence of the gain, the noise, as well as their ratio, the gain
      to-noise ratio, which measures how reliably a network transmits signals at
      different frequencies. We find that both coherent and incoherent feed-forward
      motifs can either act as low-pass or high-pass filters for information: The
      frequency dependence of the gain-to-noise ratio increases or decreases with
      increasing frequency, respectively. Our analysis of diamond motifs reveals that
      cooperative activation of the output component can increase the gain-to-noise
      ratio. This means that from the perspective of information transmission, it can
      be beneficial to split the input signal in two and recombine the two propagated
      signals at the output. Cooperative activation can be implemented via the
      formation of homo- or heteromultimers that then bind and activate the output
      component or via the binding of individual molecules of the intermediate species
      to the output component.

PMID- 23005792
TI  - Excitation energy transfer modulated by oscillating electronic coupling of a
      dimeric system embedded in a molecular environment.
AB  - We have developed a theoretical formulation for excitation energy transfer
      between structurally fluctuating dimer molecules in surrounding environments. On
      the basis of a generalized master equation in which a memory function plays a
      vital role, the temporal evolutions of the population densities of exciton at the
      donor and acceptor sites are described. By employing an ansatz form for the
      memory function, the competitive effects of dimeric coupling and bath modes are
      analyzed quantitatively, where the roles of oscillating electronic coupling are
      highlighted.

PMID- 23005793
TI  - Mode-locking dynamics of hair cells of the inner ear.
AB  - We explore mode locking of spontaneous oscillations of saccular hair cell bundles
      to periodic mechanical deflections. A simple dynamic systems framework is
      presented that captures the main features of the experimentally observed behavior
      in the form of an Arnold tongue. We propose that the phase-locking transition can
      proceed via different bifurcations. At low stimulus amplitudes F, the transition
      to mode locking as a function of the stimulus frequency omega has the character
      of a saddle-node bifurcation on an invariant circle. At higher stimulus
      amplitudes, the mode-locking transition has the character of a supercritical
      Andronov-Hopf bifurcation.

PMID- 23005794
TI  - Concentration fluctuations and phase transitions in coupled modulated bilayers.
AB  - We consider the formation of finite-size domains in lipid bilayers consisting of
      saturated and hybrid lipids. First, we describe a monolayer model that includes a
      coupling between a compositional scalar field and a two-dimensional vectorial
      order parameter. Such a coupling yields an effective two-dimensional
      microemulsion free energy for the lipid monolayer, and its characteristic length
      of compositional modulations can be considered as the origin of finite-size
      domains in biological membranes. Next, we consider a coupled bilayer composed of
      two modulated monolayers and discuss the static and dynamic properties of
      concentration fluctuations above the transition temperature. We also investigate
      the micro-phase separation below the transition temperature and compare the micro
      phase separated structures with statics and dynamics of concentration
      fluctuations above the transition.

PMID- 23005795
TI  - Dynamical principles of cell-cycle arrest: reversible, irreversible, and mixed
      strategies.
AB  - Living cells often alternate between proliferating and nonproliferating states as
      part of individual or collective strategies to adapt to complex and changing
      environments. To this aim, they have evolved a biochemical regulatory network
      enabling them to switch between cell-division cycles (i.e., oscillatory state)
      and cell-cycle arrests (i.e., steady state) in response to extracellular cues.
      This can be achieved by means of a variety of bifurcation mechanisms that
      potentially give rise to qualitatively distinct cell-cycle arrest properties. In
      this paper, we study the dynamics of a minimal biochemical network model in which
      a cell-division oscillator and a differentiation switch mutually antagonize. We
      identify the existence of three biologically plausible bifurcation scenarios
      organized around a codimension-four swallowtail-homoclinic singularity. As a
      result, the model exhibits a broad repertoire of cell-cycle arrest properties in
      terms of reversibility of these arrests, tunability of interdivision time, and
      ability to track time-varying signals. This dynamic versatility would explain the
      diversity of cell-cycle arrest strategies developed in different living species
      and functional contexts.

PMID- 23005796
TI  - Path-preference cellular-automaton model for traffic flow through transit points
      and its application to the transcription process in human cells.
AB  - We all use path routing everyday as we take shortcuts to avoid traffic jams, or
      by using faster traffic means. Previous models of traffic flow of RNA polymerase
      II (RNAPII) during transcription, however, were restricted to one dimension along
      the DNA template. Here we report the modeling and application of traffic flow in
      transcription that allows preferential paths of different dimensions only
      restricted to visit some transit points, as previously introduced between the 5'
      and 3' end of the gene. According to its position, an RNAPII protein molecule
      prefers paths obeying two types of time-evolution rules. One is an asymmetric
      simple exclusion process (ASEP) along DNA, and the other is a three-dimensional
      jump between transit points in DNA where RNAPIIs are staying. Simulations based
      on our model, and comparison experimental results, reveal how RNAPII molecules
      are distributed at the DNA-loop-formation-related protein binding sites as well
      as CTCF insulator proteins (or exons). As time passes after the stimulation, the
      RNAPII density at these sites becomes higher. Apparent far-distance jumps in one
      dimension are realized by short-range three-dimensional jumps between DNA loops.
      We confirm the above conjecture by applying our model calculation to the SAMD4A
      gene by comparing the experimental results. Our probabilistic model provides
      possible scenarios for assembling RNAPII molecules into transcription factories,
      where RNAPII and related proteins cooperatively transcribe DNA.

PMID- 23005797
TI  - Spin-oscillator model for the unzipping of biomolecules by mechanical force.
AB  - A spin-oscillator system models unzipping of biomolecules (such as DNA, RNA, or
      proteins) subject to an external force. The system comprises a macroscopic degree
      of freedom, represented by a one-dimensional oscillator, and internal degrees of
      freedom, represented by Glauber spins with nearest-neighbor interaction and a
      coupling constant proportional to the oscillator position. At a critical value
      F(c) of an applied external force F, the oscillator rest position (order
      parameter) changes abruptly and the system undergoes a first-order phase
      transition. When the external force is cycled at different rates, the extension
      given by the oscillator position exhibits a hysteresis cycle at high loading
      rates, whereas it moves reversibly over the equilibrium force-extension curve at
      very low loading rates. Under constant force, the logarithm of the residence time
      at the stable and metastable oscillator rest position is proportional to F-F(c)
      as in an Arrhenius law.

PMID- 23005798
TI  - Distributed control in a mean-field cortical network model: implications for
      seizure suppression.
AB  - Brain electrical stimulation (BES) has long been suggested as a means of
      controlling pathological brain activity. In epilepsy, control of a spatially
      localized source, the seizure focus, may normalize neuronal dynamics.
      Consequently, most BES research has been directed at controlling small, local,
      neuronal populations. At a higher level, pathological seizure activity can be
      viewed as a network event that may begin without a clear spatial focus or in
      multiple sites and spread rapidly through a distributed cortical network. In this
      paper, we begin to address the implications of local control in a network
      scenario. To do so, we explore the efficacy of local BES when deployed over a
      larger-scale neuronal network, for instance, using a grid of stimulating
      electrodes on the cortex. By introducing a mean-field model of neuronal
      interactions we are able to identify limitations in network controllability based
      on physiological constraints that suggest the need for more nuanced network
      control strategies.

PMID- 23005799
TI  - Going from microscopic to macroscopic on nonuniform growing domains.
AB  - Throughout development, chemical cues are employed to guide the functional
      specification of underlying tissues while the spatiotemporal distributions of
      such chemicals can be influenced by the growth of the tissue itself. These
      chemicals, termed morphogens, are often modeled using partial differential
      equations (PDEs). The connection between discrete stochastic and deterministic
      continuum models of particle migration on growing domains was elucidated by
      Baker, Yates, and Erban [Bull. Math. Biol. 72, 719 (2010)] in which the migration
      of individual particles was modeled as an on-lattice position-jump process. We
      build on this work by incorporating a more physically reasonable description of
      domain growth. Instead of allowing underlying lattice elements to instantaneously
      double in size and divide, we allow incremental element growth and splitting upon
      reaching a predefined threshold size. Such a description of domain growth
      necessitates a nonuniform partition of the domain. We first demonstrate that an
      individual-based stochastic model for particle diffusion on such a nonuniform
      domain partition is equivalent to a PDE model of the same phenomenon on a
      nongrowing domain, providing the transition rates (which we derive) are chosen
      correctly and we partition the domain in the correct manner. We extend this
      analysis to the case where the domain is allowed to change in size, altering the
      transition rates as necessary. Through application of the master equation
      formalism we derive a PDE for particle density on this growing domain and
      corroborate our findings with numerical simulations.

PMID- 23005800
TI  - Stiffness transition in anisotropic fiber nets.
AB  - We demonstrate the existence of a percolationlike stiffness transition in fiber
      networks with a bidisperse orientation distribution and with fiber densities
      clearly above the geometrical and the ordinary stiffness transition. The fibers
      are oriented parallel and perpendicular to a strain direction and they have a
      large fiber aspect ratio. The stiffness K of the fiber nets can be described by a
      scaling relation, K [proportionally] tau(alpha) g[(epsilon - epsilon(c))/tau(
      beta)], where tau is the fraction of fibers parallel to strain. g is a scaling
      function that is roughly described by a power law g(x) [proportionally ] x(gamma)
      for stiffness above the transition and by a constant below the transition. The
      transition point is characterized by qualitative changes in the distribution of
      the elastic deformation energy of the fibers, the deformation mode of the fibers,
      the effective Poisson ratio of the nets, the distribution of elastic energy on
      fibers and cross links, and the ratio of elastic and viscous dissipation energy.
      This transition opens the possibility of extreme stiffness variations with
      minimal mesh manipulations in the vicinity of the transition (i.e., a stiffness
      gate). It is possible that this transition affects the mechanical behavior of the
      cytoskeleton in cells.

PMID- 23005801
TI  - Solitons and collapse in the lambda-repressor protein.
AB  - The enterobacteria lambda phage is a paradigm temperate bacteriophage. Its
      lysogenic and lytic life cycles echo competition between the DNA binding lambda
      repressor (CI) and CRO proteins. Here we scrutinize the structure, stability, and
      folding pathways of the lambda-repressor protein, which controls the transition
      from the lysogenic to the lytic state. We first investigate the supersecondary
      helix-loop helix composition of its backbone. We use a discrete Frenet framing to
      resolve the backbone spectrum in terms of bond and torsion angles. Instead of
      four, there appears to be seven individual loops. We model the putative loops
      using an explicit soliton Ansatz. It is based on the standard soliton profile of
      the continuum nonlinear Schrodinger equation. The accuracy of the Ansatz far
      exceeds the B-factor fluctuation distance accuracy of the experimentally
      determined protein configuration. We then investigate the folding pathways and
      dynamics of the lambda-repressor protein. We introduce a coarse-grained energy
      function to model the backbone in terms of the C(alpha) atoms and the side chains
      in terms of the relative orientation of the C(beta) atoms. We describe the
      folding dynamics in terms of relaxation dynamics and find that the folded
      configuration can be reached from a very generic initial configuration. We
      conclude that folding is dominated by the temporal ordering of soliton formation.
      In particular, the third soliton should appear before the first and second.
      Otherwise, the DNA binding turn does not acquire its correct structure. We
      confirm the stability of the folded configuration by repeated heating and cooling
      simulations.

PMID- 23005802
TI  - Topology of plant-pollinator networks that are vulnerable to collapse from
      species extinction.
AB  - The ability to predict the collapse of ecological communities is of significant
      concern in light of global patterns of rapid species extinctions. Here, we use a
      recently developed dynamic Boolean network-based model of mutualistic plant
      pollinator community formation to investigate the stability of simulated
      ecological communities in the face of sequential species extinctions. We assess
      communities in terms of the relative change in biodiversity after species loss,
      and find that communities that experience a significant loss of biodiversity
      differ from more robust communities according to a number of topological
      characteristics. Notably, we show that high nestedness, a property commonly
      believed to promote community stability, may in extreme circumstances promote a
      critical over-reliance on individual species. Furthermore, the species important
      to the survival of the rest of the ecosystem occupy different positions in the
      network than less important species. Our results suggest that network measures
      may be applied to real ecosystems to yield insight into both their stability and
      the identity of potentially critical species.

PMID- 23005803
TI  - Dynamic regulation on energy landscape evolution of single-molecule protein by
      conformational fluctuation.
AB  - We formalize a theory to help explore the effect of conformational fluctuation on
      the energy landscape evolution of single-molecule protein. Using this
      formalization, we investigate the photon emission from single photoactivated
      fluorescent protein. A bimodal regulation on the energy landscape evolution was
      discovered, and its origin was attributed to slow conformational fluctuations of
      the protein matrix.

PMID- 23005804
TI  - Distributions of diffusion measures from a local mean-square displacement
      analysis.
AB  - In cell biology, time-resolved fluctuation analysis of tracer particles has
      recently gained great importance. One such method is the local mean-square
      displacement (MSD) analysis, which provides an estimate of two parameters as
      functions of time: the exponent of growth of the MSD and the diffusion
      coefficient. Here, we study the joint and marginal distributions of these
      parameters for Brownian motion with Gaussian velocity fluctuations, including the
      cases of vanishing correlations (overdamped Brownian motion) and of a finite
      negative velocity correlation (as observed in intracellular motion). Numerically,
      we demonstrate that a small number of MSD points is optimal for the estimation of
      the diffusion measures. Motivated by this observation, we derive an analytic
      approximation for the joint and marginal probability densities of the exponent
      and diffusion coefficient for the special case of two MSD points. These
      analytical results show good agreement with numerical simulations for
      sufficiently large window sizes. Our results might promote better statistical
      analysis of intracellular motility.

PMID- 23005805
TI  - Application of hyperbolic scaling for calculation of reaction-subdiffusion front
      propagation.
AB  - A technique of hyperbolic scaling is applied to calculate a reaction front
      velocity in an irreversible autocatalytic conversion reaction A+B -> 2A under
      subdiffusion. The method, based on the geometric optics approach is a technically
      elegant observation of the propagation front failure obtained in Phys. Rev. E 78,
      011128 (2008).

PMID- 23005806
TI  - Anomalous diffusion and long-range correlations in the score evolution of the
      game of cricket.
AB  - We investigate the time evolution of the scores of the second most popular sport
      in the world: the game of cricket. By analyzing, event by event, the scores of
      more than 2000 matches, we point out that the score dynamics is an anomalous
      diffusive process. Our analysis reveals that the variance of the process is
      described by a power-law dependence with a superdiffusive exponent, that the
      scores are statistically self-similar following a universal Gaussian
      distribution, and that there are long-range correlations in the score evolution.
      We employ a generalized Langevin equation with a power-law correlated noise that
      describes all the empirical findings very well. These observations suggest that
      competition among agents may be a mechanism leading to anomalous diffusion and
      long-range correlation.

PMID- 23005807
TI  - Weakly anomalous diffusion with non-Gaussian propagators.
AB  - A poorly understood phenomenon seen in complex systems is diffusion characterized
      by Hurst exponent H ~ 1/2 but with non-Gaussian statistics. Motivated by such
      empirical findings, we report an exact analytical solution for a non-Markovian
      random walk model that gives rise to weakly anomalous diffusion with H = 1/2 but
      with a non-Gaussian propagator.

PMID- 23005808
TI  - Imaginary fixed points can be physical.
AB  - It has been proposed that a first-order phase transition driven to happen in the
      metastable region exhibits scaling and universality near an instability point
      controlled by an instability fixed point of a phi(3) theory. However, this fixed
      point has an imaginary value and the renormalization-group flow of the phi(3)
      coupling diverges at a finite scale. Here combining a momentum-space RG analysis
      and a nucleation theory near the spinodal point, we show that imaginary rather
      than real values are physical counterintuitively and thus the imaginary fixed
      point does control the scaling.

PMID- 23005809
TI  - Scaling of cluster heterogeneity in the two-dimensional Potts model.
AB  - Cluster heterogeneity, the number of clusters of mutually distinct sizes, has
      been recently studied for explosive percolation and standard percolation [H. K.
      Lee et al., Phys. Rev. E 84, 020101(R) (2011); J. D. Noh et al., Phys. Rev. E 84,
      010101(R) (2011)]. In this work we study the scaling of various quantities
      related with cluster heterogeneity in a broader context of two-dimensional q
      state Potts model. We predict, via an analytic approach, the critical exponents
      for most of the measured quantities, and confirm these predications for various q
      values using extensive Monte Carlo simulations.

PMID- 23005810
TI  - Electric-double-layer structure close to the three-phase contact line in an
      electrolyte wetting a solid substrate.
AB  - The electric-double-layer structure in an electrolyte close to a solid substrate
      near the three-phase contact line is approximated by considering the linearized
      Poisson-Boltzmann equation in a wedge geometry. The mathematical approach
      complements the semianalytical solutions reported in the literature by providing
      easily available characteristic information on the double-layer structure. In
      particular, the model contains a length scale that quantifies the distance from
      the fluid-fluid interface over which this boundary influences the electric double
      layer. The analysis is based on an approximation for the equipotential lines.
      Excellent agreement between the model predictions and numerical results is
      achieved for a significant range of contact angles. The length scale quantifying
      the influence of the fluid-fluid interface is proportional to the Debye length
      and depends on the wall contact angle. It is shown that for contact angles
      approaching 90 degrees  there is a finite range of boundary influence.

PMID- 23005811
TI  - Mechanical and optical bending of nematic elastomer cantilevers.
AB  - We describe how bend imposed on a nematic elastomer cantilever can be
      accommodated with little or no internal stress by the director rotating. Thus,
      for a range of imposed curvatures that we calculate, there is no countertorque.
      Equally nonclassically, in such beams there is associated transverse curvature
      (clasticity). When instead bend is induced by illumination which causes spatially
      dependent contractions, director rotation can also act to vitiate stresses, but
      then (anti-)clasticity and its suppression has to be resolved, sometimes at the
      cost of stress creation.

PMID- 23005812
TI  - Topological versus rheological entanglement length in primitive-path analysis
      protocols, tube models, and slip-link models.
AB  - We show that the front factor appearing in the shear modulus of a phantom
      network, G(ph) = (1-2/f)(rhok(B)T)/N(s), also controls the ratio of the strand
      length, N(s), and the number of monomers per Kuhn length of the primitive paths,
      N(ph)(PPKuhn), characterizing the average network conformation. In particular,
      N(ph)(PPKuhn) = N(s)/(1-2/f) and G(ph) = (rhok(B)T)/N(ph)(PPKuhn). Neglecting the
      difference between cross-links and slip-links, these results can be transferred
      to entangled systems and the interpretation of primitive path analysis data. In
      agreement with the tube model, the analogy to phantom networks suggest that the
      rheological entanglement length, N(e)(rheo) = (rhok(B)T)/G(e), should equal
      N(e)(PPKuhn). Assuming binary entanglements with f = 4 functional junctions, we
      expect that N(e)(rheo) should be twice as large as the topological entanglement
      length, N(e)(topo). These results are in good agreement with reported primitive
      path analysis results for model systems and a wide range of polymeric materials.
      Implications for tube and slip-link models are discussed.

PMID- 23005813
TI  - Comment on "Time needed to board an airplane: a power law and the structure
      behind it".
AB  - Frette and Hemmer [Phys. Rev. E 85, 011130 (2012)] recently showed that for a
      simple model for the boarding of an airplane, the mean time to board scales as a
      power law with the number of passengers N and the exponent is less than 1. They
      note that this scaling leads to the prediction that the "back-to-front" strategy,
      where passengers are divided into groups from contiguous ranges of rows and each
      group is allowed to board in turn from back to front once the previous group has
      found their seats, has a longer boarding time than would a single group. Here I
      extend their results to a larger number of passengers using a sampling approach
      and explore a scenario where the queue is presorted into groups from back to
      front, but allowed to enter the plane as soon as they can. I show that the power
      law dependence on passenger numbers is different for large N and that there is a
      boarding time reduction for presorted groups, with a power law dependence on the
      number of presorted groups.

PMID- 23005814
TI  - Onset of localization in heterogeneous interfacial failure.
AB  - We study numerically the failure of an interface joining two elastic materials
      under load using a fiber bundle model connected to an elastic half space. We find
      that the breakdown process follows the equal load sharing fiber bundle model
      without any detectable spatial correlations between the positions of the failing
      fibers until localization sets in. Depending on the elastic constant describing
      the elastic half space, localization sets in before or after the critical load
      causing the interface to fail completely is reached. There is a crossover between
      failure due to localization and failure without spatial correlations when tuning
      the elastic constant, not a phase transition as has been proposed earlier. Also,
      contrary to earlier claims based on models different from ours, we find that a
      finite fraction of fibers must fail before the critical load is attained, even in
      the extreme localization regime, i.e., for very small elastic constant. We
      furthermore find that the critical load remains finite for all values of the
      elastic constant in the limit of an infinitely large system.

PMID- 23005815
TI  - Probabilistic convergence guarantees for type-II pulse-coupled oscillators.
AB  - We show that a large class of pulse-coupled oscillators converge with high
      probability from random initial conditions on a large class of graphs with time
      delays. Our analysis combines previous local convergence results, probabilistic
      network analysis, and a classification scheme for type-II phase response curves
      to produce rigorous lower bounds for convergence probabilities based on network
      density. These results suggest methods for the analysis of pulse-coupled
      oscillators, and provide insights into the balance of excitation and inhibition
      in the operation of biological type-II phase response curves and also the design
      of decentralized and minimal clock synchronization schemes in sensor nets.

PMID- 23005816
TI  - Computation of anomalous scaling exponents of turbulence from self-similar
      instanton dynamics.
AB  - We show that multiscaling properties of developed turbulence in shell models,
      which lead to anomalous scaling exponents in the inertial range, are determined
      exclusively by instanton dynamics. Instantons represent correlated extreme events
      localized in space-time, whose structure is described by self-similar statistics
      with a single universal scaling exponent. We show that anomalous scaling
      exponents appear due to the process of instanton creation. A simplified model of
      instanton creation is suggested, which adequately describes this anomaly.

PMID- 23005817
TI  - Pressure-driven flow through a single nanopore.
AB  - We have measured the flow of gas through single ion track pores in a polymer film
      using a mass spectroscopy technique. The pores are 12 MUm long with diameters in
      the range of 50-1000 nm, and the flow was driven by pressure drops in the range 0
      30 atm. When the mean free path is large compared to the pore diameter (large
      Knudsen number Kn), the flow rate is proportional to the pressure drop and the
      pore radius R cubed, and is consistent with a model of diffusive scattering at
      the pore walls. For Kn<=0.1, the hydrodynamic conductance increases, as predicted
      by standard kinetic theory models, and finally approaches the conventional
      Poiseuille value with zero slip length.

PMID- 23005818
TI  - Allowed and forbidden regimes of entropy balance in lattice Boltzmann collisions.
AB  - We study the possibility of modifying collisions in the lattice Boltzmann method
      to keep the proper entropy balance. We demonstrate that in the space of
      distributions operated on by lattice Boltzmann methods which respect a Boltzmann
      type H theorem, there exists a vicinity of the equilibrium where collisions with
      entropy balance are possible and, at the same time, there exists a region of
      nonequilibrium distributions where such collisions are impossible. In particular,
      for a strictly concave and uniformly bounded entropy function with positive
      equilibria, we show that proper entropy balance is always possible sufficiently
      close to the local equilibrium and it is impossible sufficiently far from it,
      where additional dissipation has to appear. We also present some nonclassical
      entropies that do not share this concern. The cases where the distribution enters
      the region far from equilibrium typically occur in flows with low viscosity
      and/or high Mach number flows and in simulations on coarse grids.

PMID- 23005819
TI  - Correlation and network analysis of global financial indices.
AB  - Random matrix theory (RMT) and network methods are applied to investigate the
      correlation and network properties of 20 financial indices. The results are
      compared before and during the financial crisis of 2008. In the RMT method, the
      components of eigenvectors corresponding to the second largest eigenvalue form
      two clusters of indices in the positive and negative directions. The components
      of these two clusters switch in opposite directions during the crisis. The
      network analysis uses the Fruchterman-Reingold layout to find clusters in the
      network of indices at different thresholds. At a threshold of 0.6, before the
      crisis, financial indices corresponding to the Americas, Europe, and Asia-Pacific
      form separate clusters. On the other hand, during the crisis at the same
      threshold, the American and European indices combine together to form a strongly
      linked cluster while the Asia-Pacific indices form a separate weakly linked
      cluster. If the value of the threshold is further increased to 0.9 then the
      European indices (France, Germany, and the United Kingdom) are found to be the
      most tightly linked indices. The structure of the minimum spanning tree of
      financial indices is more starlike before the crisis and it changes to become
      more chainlike during the crisis. The average linkage hierarchical clustering
      algorithm is used to find a clearer cluster structure in the network of financial
      indices. The cophenetic correlation coefficients are calculated and found to
      increase significantly, which indicates that the hierarchy increases during the
      financial crisis. These results show that there is substantial change in the
      structure of the organization of financial indices during a financial crisis.

PMID- 23005820
TI  - Modification of the gravity model and application to the metropolitan Seoul
      subway system.
AB  - The Metropolitan Seoul Subway system is examined through the use of the gravity
      model. Exponents describing the power-law dependence on the time distance between
      stations are obtained, which reveals a universality for subway lines of the same
      topology. In the short (time) distance regime the number of passengers between
      stations does not grow with the decrease in the distance, thus deviating from the
      power-law behavior. It is found that such reduction in passengers is well
      described by the Hill function. Further, temporal fluctuations in the passenger
      flow data, fitted to the gravity model modified by the Hill function, are
      analyzed to reveal the Yule-type nature inherent in the structure of Seoul.

PMID- 23005821
TI  - Emergence of patterns in random processes.
AB  - Sixty years ago, it was observed that any independent and identically distributed
      (i.i.d.) random variable would produce a pattern of peak-to-peak sequences with,
      on average, three events per sequence. This outcome was employed to show that
      randomness could yield, as a null hypothesis for animal populations, an
      explanation for their apparent 3-year cycles. We show how we can explicitly
      obtain a universal distribution of the lengths of peak-to-peak sequences in time
      series and that this can be employed for long data sets as a test of their i.i.d.
      character. We illustrate the validity of our analysis utilizing the peak-to-peak
      statistics of a Gaussian white noise. We also consider the nearest-neighbor
      cluster statistics of point processes in time. If the time intervals are random,
      we show that cluster size statistics are identical to the peak-to-peak sequence
      statistics of time series. In order to study the influence of correlations in a
      time series, we determine the peak-to-peak sequence statistics for the Langevin
      equation of kinetic theory leading to Brownian motion. To test our methodology,
      we consider a variety of applications. Using a global catalog of earthquakes, we
      obtain the peak-to-peak statistics of earthquake magnitudes and the nearest
      neighbor interoccurrence time statistics. In both cases, we find good agreement
      with the i.i.d. theory. We also consider the interval statistics of the Old
      Faithful geyser in Yellowstone National Park. In this case, we find a significant
      deviation from the i.i.d. theory which we attribute to antipersistence. We
      consider the interval statistics using the AL index of geomagnetic substorms. We
      again find a significant deviation from i.i.d. behavior that we attribute to mild
      persistence. Finally, we examine the behavior of Standard and Poor's 500 stock
      index's daily returns from 1928-2011 and show that, while it is close to being
      i.i.d., there is, again, significant persistence. We expect that there will be
      many other applications of our methodology both to interoccurrence statistics and
      to time series.

PMID- 23005822
TI  - Transmission of packets on a hierarchical network: statistics and explosive
      percolation.
AB  - We analyze an idealized model for the transmission or flow of particles, or
      discrete packets of information, in a weight bearing branching hierarchical two
      dimensional network and its variants. The capacities add hierarchically down the
      clusters. Each node can accommodate a limited number of packets, depending on its
      capacity, and the packets hop from node to node, following the links between the
      nodes. The statistical properties of this system are given by the Maxwell
      Boltzmann distribution. We obtain analytical expressions for the mean occupation
      numbers as functions of capacity, for different network topologies. The
      analytical results are shown to be in agreement with the numerical simulations.
      The traffic flow in these models can be represented by the site percolation
      problem. It is seen that the percolation transitions in the 2D model and in its
      variant lattices are continuous transitions, whereas the transition is found to
      be explosive (discontinuous) for the V lattice, the critical case of the 2D
      lattice. The scaling behavior of the second-order percolation case is studied in
      detail. We discuss the implications of our analysis.

PMID- 23005823
TI  - Stability and robustness analysis of cooperation cycles driven by destructive
      agents in finite populations.
AB  - The emergence and promotion of cooperation are two of the main issues in
      evolutionary game theory, as cooperation is amenable to exploitation by
      defectors, which take advantage of cooperative individuals at no cost, dooming
      them to extinction. It has been recently shown that the existence of purely
      destructive agents (termed jokers) acting on the common enterprises (public goods
      games) can induce stable limit cycles among cooperation, defection, and
      destruction when infinite populations are considered. These cycles allow for time
      lapses in which cooperators represent a relevant fraction of the population,
      providing a mechanism for the emergence of cooperative states in nature and human
      societies. Here we study analytically and through agent-based simulations the
      dynamics generated by jokers in finite populations for several selection rules.
      Cycles appear in all cases studied, thus showing that the joker dynamics
      generically yields a robust cyclic behavior not restricted to infinite
      populations. We also compute the average time in which the population consists
      mostly of just one strategy and compare the results with numerical simulations.

PMID- 23005824
TI  - Epidemic spreading on interconnected networks.
AB  - Many real networks are not isolated from each other but form networks of
      networks, often interrelated in nontrivial ways. Here, we analyze an epidemic
      spreading process taking place on top of two interconnected complex networks. We
      develop a heterogeneous mean-field approach that allows us to calculate the
      conditions for the emergence of an endemic state. Interestingly, a global endemic
      state may arise in the coupled system even though the epidemics is not able to
      propagate on each network separately and even when the number of coupling
      connections is small. Our analytic results are successfully confronted against
      large-scale numerical simulations.

PMID- 23005825
TI  - Viability of an elementary syntactic structure in a population playing naming
      games.
AB  - We explore how the social dynamics of communication and learning can bring about
      the rise of a syntactic communication in a population of speakers. Our study is
      developed starting from a version of the Naming Game model in which an elementary
      syntactic structure is introduced. This analysis shows how the transition from
      nonsyntactic to syntactic communication is socially favored in communities which
      need to exchange a large number of concepts.

PMID- 23005826
TI  - Network structure, topology, and dynamics in generalized models of
      synchronization.
AB  - Network structure is a product of both its topology and interactions between its
      nodes. We explore this claim using the paradigm of distributed synchronization in
      a network of coupled oscillators. As the network evolves to a global steady
      state, nodes synchronize in stages, revealing the network's underlying community
      structure. Traditional models of synchronization assume that interactions between
      nodes are mediated by a conservative process similar to diffusion. However,
      social and biological processes are often nonconservative. We propose a model of
      synchronization in a network of oscillators coupled via nonconservative
      processes. We study the dynamics of synchronization of a synthetic and real-world
      networks and show that the traditional and nonconservative models of
      synchronization reveal different structures within the same network.

PMID- 23005827
TI  - Phase transition to a two-peak phase in an information-cascade voting experiment.
AB  - Observational learning is an important information aggregation mechanism.
      However, it occasionally leads to a state in which an entire population chooses a
      suboptimal option. When this occurs and whether it is a phase transition remain
      unanswered. To address these questions we perform a voting experiment in which
      subjects answer a two-choice quiz sequentially with and without information about
      the prior subjects' choices. The subjects who could copy others are called
      herders. We obtain a microscopic rule regarding how herders copy others. Varying
      the ratio of herders leads to qualitative changes in the macroscopic behavior of
      about 50 subjects in the experiment. If the ratio is small, the sequence of
      choices rapidly converges to the correct one. As the ratio approaches 100%,
      convergence becomes extremely slow and information aggregation almost terminates.
      A simulation study of a stochastic model for 10(6) subjects based on the herder's
      microscopic rule shows a phase transition to the two-peak phase, where the
      convergence completely terminates as the ratio exceeds some critical value.

PMID- 23005828
TI  - Information storage, loop motifs, and clustered structure in complex networks.
AB  - We use a standard discrete-time linear Gaussian model to analyze the information
      storage capability of individual nodes in complex networks, given the network
      structure and link weights. In particular, we investigate the role of two- and
      three-node motifs in contributing to local information storage. We show
      analytically that directed feedback and feedforward loop motifs are the dominant
      contributors to information storage capability, with their weighted motif counts
      locally positively correlated to storage capability. We also reveal the direct
      local relationship between clustering coefficient(s) and information storage.
      These results explain the dynamical importance of clustered structure and offer
      an explanation for the prevalence of these motifs in biological and artificial
      networks.

PMID- 23005829
TI  - Reactant-product quantum coherence in electron transfer reactions.
AB  - We investigate the physical meaning of quantum superposition states between
      reactants and products in electron transfer reactions. We show that such
      superpositions are strongly suppressed and, to leading orders of perturbation
      theory, do not pertain in electron transfer reactions. This is because of the
      intermediate manifold of states separating the reactants from the products. We
      provide an intuitive description of these considerations with Feynman diagrams.
      We also discuss the relation of such quantum coherences to understanding the
      fundamental quantum dynamics of spin-selective radical-ion-pair reactions.

PMID- 23005830
TI  - Encoding dynamics for multiscale community detection: Markov time sweeping for
      the map equation.
AB  - The detection of community structure in networks is intimately related to finding
      a concise description of the network in terms of its modules. This notion has
      been recently exploited by the map equation formalism [Rosvall and Bergstrom,
      Proc. Natl. Acad. Sci. USA 105, 1118 (2008)] through an information-theoretic
      description of the process of coding inter- and intracommunity transitions of a
      random walker in the network at stationarity. However, a thorough study of the
      relationship between the full Markov dynamics and the coding mechanism is still
      lacking. We show here that the original map coding scheme, which is both block
      averaged and one-step, neglects the internal structure of the communities and
      introduces an upper scale, the "field-of-view" limit, in the communities it can
      detect. As a consequence, map is well tuned to detect clique-like communities but
      can lead to undesirable overpartitioning when communities are far from clique
      like. We show that a signature of this behavior is a large compression gap: The
      map description length is far from its ideal limit. To address this issue, we
      propose a simple dynamic approach that introduces time explicitly into the map
      coding through the analysis of the weighted adjacency matrix of the time
      dependent multistep transition matrix of the Markov process. The resulting Markov
      time sweeping induces a dynamical zooming across scales that can reveal
      (potentially multiscale) community structure above the field-of-view limit, with
      the relevant partitions indicated by a small compression gap.

PMID- 23005831
TI  - Network-based criterion for the success of cooperation in an evolutionary
      prisoner's dilemma.
AB  - We consider an evolutionary prisoner's dilemma on a random network. We introduce
      a simple quantitative network-based parameter and show that it effectively
      predicts the success of cooperation in simulations on the network. The criterion
      is shown to be accurate on a variety of networks with degree distributions
      ranging from regular to Poisson to scale free. The parameter allows for
      comparisons of random networks regardless of their underlying topology. Finally,
      we draw analogies between the criterion for the success of cooperation introduced
      here and existing criteria in other contexts.

PMID- 23005832
TI  - Binary threshold networks as a natural null model for biological networks.
AB  - Spin models of neural networks and genetic networks are considered elegant as
      they are accessible to statistical mechanics tools for spin glasses and magnetic
      systems. However, the conventional choice of variables in spin systems may cause
      problems in some models when parameter choices are unrealistic from a biological
      perspective. Obviously, this may limit the role of a model as a template model
      for biological systems. Perhaps less obviously, also ensembles of random networks
      are affected and may exhibit different critical properties. We consider here a
      prototypical network model that is biologically plausible in its local
      mechanisms. We study a discrete dynamical network with two characteristic
      properties: Nodes with binary states 0 and 1, and a modified threshold function
      with Theta(0)(0)=0. We explore the critical properties of random networks of such
      nodes and find a critical connectivity K(c)=2.0 with activity vanishing at the
      critical point. Finally, we observe that the present model allows a more natural
      implementation of recent models of budding yeast and fission yeast cell-cycle
      control networks.

PMID- 23005833
TI  - Epidemic spreading induced by diversity of agents' mobility.
AB  - In this paper, we study the impact of the preference of an individual for public
      transport on the spread of infectious disease, through a quantity known as the
      public mobility. Our theoretical and numerical results based on a constructed
      model reveal that if the average public mobility of the agents is fixed, an
      increase in the diversity of the agents' public mobility reduces the epidemic
      threshold, beyond which an enhancement in the rate of infection is observed. Our
      findings provide an approach to improve the resistance of a society against
      infectious disease, while preserving the utilization rate of the public
      transportation system.

PMID- 23005834
TI  - Susceptible-infected-susceptible model: a comparison of N-intertwined and
      heterogeneous mean-field approximations.
AB  - We introduce the epsilon-susceptible-infected-susceptible (SIS) spreading model,
      which is taken as a benchmark for the comparison between the N-intertwined
      approximation and the Pastor-Satorras and Vespignani heterogeneous mean-field
      (HMF) approximation of the SIS model. The N-intertwined approximation, the HMF
      approximation, and the epsilon-SIS spreading model are compared for different
      graph types. We focus on the epidemic threshold and the steady-state fraction of
      infected nodes in networks with different degree distributions. Overall, the N
      intertwined approximation is superior to the HMF approximation. The N-intertwined
      approximation is exactly the same as the HMF approximation in regular graphs.
      However, for some special graph types, such as the square lattice graph and the
      path graph, the two mean-field approximations are both very different from the
      epsilon-SIS spreading model.

PMID- 23005835
TI  - Slow dynamics and rare-region effects in the contact process on weighted tree
      networks.
AB  - We show that generic, slow dynamics can occur in the contact process on complex
      networks with a tree-like structure and a superimposed weight pattern, in the
      absence of additional (nontopological) sources of quenched disorder. The slow
      dynamics is induced by rare-region effects occurring on correlated subspaces of
      vertices connected by large weight edges and manifests in the form of a smeared
      phase transition. We conjecture that more sophisticated network motifs could be
      able to induce Griffiths phases, as a consequence of purely topological disorder.

PMID- 23005836
TI  - Pedestrian flow through multiple bottlenecks.
AB  - We investigate the dynamics of the evacuation process with multiple bottlenecks
      using the floor field model. To deal with this problem, we first focus on a part
      of the system and report its microscopic behavior. The system is controlled by
      parameters of inflow and the competitiveness of the pedestrians, and large inflow
      leads to a congested situation. Through simulations, the metastable state induced
      by conflicts of pedestrians is observed. The metastability is related to the
      phase transition from free flow to congestion. The critical condition of the
      transition is theoretically derived. In addition, we give simulation results of
      situations with multiple bottlenecks. They imply that local improvement of
      pedestrian flow sometimes adversely affects the total evacuation time, and that
      the total optimization of the system is not straightforward.

PMID- 23005837
TI  - Shape of an elastic loop strongly bent by surface tension: experiments and
      comparison with theory.
AB  - When a very flexible wire is dipped into a soapy solution, it collapses onto
      itself. We consider the regions of high curvature where the wire folds back onto
      itself, enclosing a capillary film. The shapes of these end loops are measured in
      experiments using soap films and compared to a known similarity solution. The
      sizes of these structures provide a simple and reliable way to measure surface
      tension.

PMID- 23005838
TI  - Clustering of random scale-free networks.
AB  - We derive the finite-size dependence of the clustering coefficient of scale-free
      random graphs generated by the configuration model with degree distribution
      exponent 2<gamma<3. Degree heterogeneity increases the presence of triangles in
      the network up to levels that compare to those found in many real networks even
      for extremely large nets. We also find that for values of gamma~2, clustering is
      virtually size independent and, at the same time, becomes a de facto non-self
      averaging topological property. This implies that a single-instance network is
      not representative of the ensemble even for very large network sizes.

PMID- 23005839
TI  - Nonlinear effects on Turing patterns: time oscillations and chaos.
AB  - We show that a model reaction-diffusion system with two species in a monostable
      regime and over a large region of parameter space produces Turing patterns
      coexisting with a limit cycle which cannot be discerned from the linear analysis.
      As a consequence, the patterns oscillate in time. When varying a single
      parameter, a series of bifurcations leads to period doubling, quasiperiodic, and
      chaotic oscillations without modifying the underlying Turing pattern. A Ruelle
      Takens-Newhouse route to chaos is identified. We also examine the Turing
      conditions for obtaining a diffusion-driven instability and show that the
      patterns obtained are not necessarily stationary for certain values of the
      diffusion coefficients. These results demonstrate the limitations of the linear
      analysis for reaction-diffusion systems.

PMID- 23005840
TI  - Trace formula for dielectric cavities. III. TE modes.
AB  - The construction of the semiclassical trace formula for resonances with
      transverse electric polarization for two-dimensional dielectric cavities is
      discussed. Special attention is given to the derivation of the two first terms of
      Weyl's series for the average number of such resonances. The formulas obtained
      agree well with numerical calculations for dielectric cavities of different
      shapes.

PMID- 23005841
TI  - Estimating network topology by the mean first-passage time.
AB  - In this work, we employed the concept of the first-passage time in stochastic
      processes to estimate node degrees and the degree distribution of a network. A
      statistical exploration of the coupling reveals the relation between the node
      degree and the coupling term. In practical terms, an effective way to reveal the
      statistical property is to investigate the differences between coupled
      oscillators in a network and uncoupled ones with the same initial states. We
      discovered a monotonically decreasing relation between the node degree and the
      mean first-passage time (MFPT) for the evolution of the coupled node deviating
      from the uncoupled one. Moreover, this relation can be understood as the
      competition of different relaxational time scales. The MFPT method is independent
      of both the dynamics of the nodes and the topological properties of the network.
      This might be advantageous in our efforts to build a bridge between the
      topological property and the dynamics of a network.

PMID- 23005842
TI  - Phase-reduction-theory-based treatment of extended delayed feedback control
      algorithm in the presence of a small time delay mismatch.
AB  - The delayed feedback control (DFC) methods are noninvasive, which means that the
      control signal vanishes if the delay time is adjusted to be equal to the period
      of a target unstable periodic orbit (UPO). If the delay time differs slightly
      from the UPO period, a nonvanishing periodic control signal is observed. We
      derive an analytical expression for this period for a general class of multiple
      input multiple-output systems controlled by an extended DFC algorithm. Our
      approach is based on the phase-reduction theory adapted to systems with time
      delay. The analytical results are supported by numerical simulations of the
      controlled Rossler system.

PMID- 23005843
TI  - Influence of the singular manifold of nonobservable states in reconstructing
      chaotic attractors.
AB  - It is known that the reconstructed phase portrait of a given system strongly
      depends on the choice of the observable. In particular, the ability to obtain a
      global model from a time series strongly depends on the observability provided by
      the measured variable. Such a dependency results from (i) the existence of a
      singular observability manifold, M(s)(obs), for which the coordinate
      transformation between R(m) and the reconstructed space is not defined and (ii)
      how often the trajectory visits the neighborhood U(M(s)(obs)) of M(s)(obs). In
      order to clarify how these aspects contribute to the observability coefficients,
      we introduce the probability of visits of M(s)(obs) and the relative time spent
      in U(M(s)(obs)) to construct a new coefficient. Combined with the symbolic
      observability coefficients previously introduced [Letellier and Aguirre, Phys.
      Rev. E 79, 066210 (2009)] (only taking into account the existence of M(s)(obs)),
      this new coefficient helps to determine the specific role played by the location
      of M(s)(obs) with respect to the attractor, in phase portrait reconstruction and
      in any analysis technique.

PMID- 23005844
TI  - Perturbations and chaos in quantum maps.
AB  - The local density of states (LDOS) is a distribution that characterizes the
      effects of perturbations on quantum systems. Recently, a semiclassical theory was
      proposed for the LDOS of chaotic billiards and maps. This theory predicts that
      the LDOS is a Breit-Wigner distribution independent of the perturbation strength
      and also gives a semiclassical expression for the LDOS width. Here, we test the
      validity of such an approximation in quantum maps by varying the degree of
      chaoticity, the region in phase space where the perturbation is applied, and the
      intensity of the perturbation. We show that for highly chaotic maps or strong
      perturbations the semiclassical theory of the LDOS is accurate to describe the
      quantum distribution. Moreover, the width of the LDOS is also well represented
      for its semiclassical expression in the case of mixed classical dynamics.

PMID- 23005845
TI  - Prediction of catastrophes: an experimental model.
AB  - Catastrophes of all kinds can be roughly defined as short-duration, large
      amplitude events following and followed by long periods of "ripening." Major
      earthquakes surely belong to the class of "catastrophic" events. Because of the
      space-time scales involved, an experimental approach is often difficult, not to
      say impossible, however desirable it could be. Described in this article is a
      "laboratory" setup that yields data of a type that is amenable to theoretical
      methods of prediction. Observations are made of a critical slowing down in the
      noisy signal of a solder wire creeping under constant stress. This effect is
      shown to be a fair signal of the forthcoming catastrophe in two separate
      dynamical models. The first is an "abstract" model in which a time-dependent
      quantity drifts slowly but makes quick jumps from time to time. The second is a
      realistic physical model for the collective motion of dislocations (the
      Ananthakrishna set of equations for unstable creep). Hope thus exists that
      similar changes in the response to noise could forewarn catastrophes in other
      situations, where such precursor effects should manifest early enough.

PMID- 23005846
TI  - Blocking and transmission of traveling flow-distributed-oscillation waves in an
      absolutely unstable flowing medium.
AB  - For a flowing, self-oscillating medium, we study the competition between
      traveling flow-distributed-oscillation waves excited by periodic driving at the
      upstream boundary and bulk oscillations originating downstream from the boundary.
      As previously observed in the case of stationary driving, we find that there is a
      region in parameter space where boundary-driven traveling waves of sufficiently
      high amplitude can impose themselves on the entire medium despite the presence of
      an absolute instability, which otherwise tends to block information from
      upstream. For sufficiently low flow rates, however, the imposed waves are
      arrested at a nonlinear blocking transition. Unlike the stationary case, we find
      that the region of imposed waves extends well into regions where, according to
      the linear approximation, there should be no traveling waves at all. This
      suggests that the extinction of the traveling waves is analogous to a subcritical
      Hopf bifurcation.

PMID- 23005847
TI  - Dripping faucet dynamics is determined by synchronization of drop oscillations
      and detachment.
AB  - A dripping faucet is an example of an everyday system that exhibits surprisingly
      rich dynamics ranging from periodic to chaotic. Using a simple capacitive device,
      we experimentally demonstrate that the dynamics is determined by the degree of
      synchronization between two temporally disparate processes: the time at which a
      drop attains a critical mass and an oscillatory process that accompanies the
      formation of a drop. We present a full experimental phase-space reconstruction of
      the ensuing dynamics.

PMID- 23005848
TI  - Bubble-induced damping in displacement-driven microfluidic flows.
AB  - Bubble damping in displacement-driven microfluidic flows was theoretically and
      experimentally investigated for a Y-channel microfluidic network. The system was
      found to exhibit linear behavior for typical microfluidic flow conditions. The
      bubbles induced a low-pass filter behavior with a characteristic cutoff frequency
      that scaled proportionally with flow rate and inversely with bubble volume and
      exhibited a minimum with respect to the relative resistances of the connecting
      channels. A theoretical model based on the electrical circuit analogy was able to
      predict experimentally observed damping of fluctuations with excellent agreement.
      Finally, a flowmeter with high resolution (0.01 MUL/min) was demonstrated as an
      application of the bubble-aided stabilization. This study may aid in the design
      of many other bubble-stabilized microfluidic systems.

PMID- 23005849
TI  - Theory of water and charged liquid bridges.
AB  - The phenomenon of liquid bridge formation due to an applied electric field is
      investigated. A solution of a charged catenary is presented, which allows one to
      determine the static and dynamical stability conditions where charged liquid
      bridges are possible. The creeping height, the bridge radius and length, as well
      as the shape of the bridge are calculated showing an asymmetric profile, in
      agreement with observations. The flow profile is calculated from the Navier
      Stokes equation leading to a mean velocity, which combines charge transport with
      neutral mass flow and which describes recent experiments on water bridges.

PMID- 23005850
TI  - Mean-field dynamo action in renovating shearing flows.
AB  - We study mean-field dynamo action in renovating flows with finite and nonzero
      correlation time (tau) in the presence of shear. Previous results obtained when
      shear was absent are generalized to the case with shear. The question of whether
      the mean magnetic field can grow in the presence of shear and nonhelical
      turbulence, as seen in numerical simulations, is examined. We show in a general
      manner that, if the motions are strictly nonhelical, then such mean-field dynamo
      action is not possible. This result is not limited to low (fluid or magnetic)
      Reynolds numbers nor does it use any closure approximation; it only assumes that
      the flow renovates itself after each time interval tau. Specifying to a
      particular form of the renovating flow with helicity, we recover the standard
      dispersion relation of the alpha(2)Omega dynamo, in the small tau or large
      wavelength limit. Thus mean fields grow even in the presence of rapidly growing
      fluctuations, surprisingly, in a manner predicted by the standard quasilinear
      closure, even though such a closure is not strictly justified. Our work also
      suggests the possibility of obtaining mean-field dynamo growth in the presence of
      helicity fluctuations, although having a coherent helicity will be more
      efficient.

PMID- 23005851
TI  - Excitation of inertial modes in an experimental spherical Couette flow.
AB  - Spherical Couette flow (flow between concentric rotating spheres) is one of flows
      under consideration for the laboratory magnetic dynamos. Recent experiments have
      shown that such flows may excite Coriolis restored inertial modes. The present
      work aims to better understand the properties of the observed modes and the
      nature of their excitation. Using numerical solutions describing forced inertial
      modes of a uniformly rotating fluid inside a spherical shell, we first identify
      the observed oscillations of the Couette flow with nonaxisymmetric, retrograde,
      equatorially antisymmetric inertial modes, confirming first attempts using a full
      sphere model. Although the model has no differential rotation, identification is
      possible because a large fraction of the fluid in a spherical Couette flow
      rotates rigidly. From the observed sequence of the excited modes appearing when
      the inner sphere is slowed down by step, we identify a critical Rossby number
      associated with a given mode, below which it is excited. The matching between
      this critical number and the one derived from the phase velocity of the
      numerically computed modes shows that these modes are excited by an instability
      likely driven by the critical layer that develops in the shear layer, staying
      along the tangent cylinder of the inner sphere.

PMID- 23005852
TI  - Numerical simulation of electrospray in the cone-jet mode.
AB  - We present a robust and computationally efficient numerical scheme for simulating
      steady electrohydrodynamic atomization processes (electrospray). The main
      simplification assumed in this scheme is that all the free electrical charges are
      distributed over the interface. A comparison of the results with those calculated
      with a volume-of-fluid method showed that the numerical scheme presented here
      accurately describes the flow pattern within the entire liquid domain.
      Experiments were performed to partially validate the numerical predictions. The
      simulations reproduced accurately the experimental shape of the liquid cone jet,
      providing correct values of the emitted electric current even for configurations
      very close to the cone-jet stability limit.

PMID- 23005853
TI  - Variational framework for flow optimization using seminorm constraints.
AB  - We present a general variational framework designed to consider constrained
      optimization and sensitivity analysis of spatially and temporally evolving flows
      defined as solutions of partial differential equations. We particularly focus on
      seminorm constraints which naturally arise for instance when the quantity which
      we wish to optimize can have contributions from several terms in the PDE through
      different physical mechanisms in a specific physical system. We show that this
      case implicitly requires that constraints be placed on the magnitude of
      complementary (with respect to the first constraining seminorm) seminorms of
      initial perturbations such that the sum of these complementary seminorms defines
      a total "true" norm of the state vector. A simple (true) norm constraint
      naturally satisfies this property. Therefore, the use of this framework requires
      the introduction of new parameters which describe the relative magnitude of the
      initial perturbation state vector calculated using the various constrained
      complementary seminorms to the magnitude calculated using the true norm, even for
      linear problems. We demonstrate that any required optimization has to be carried
      out by prescribing these new parameters as initial conditions on the admissible
      perturbations; the influence and significance of each seminorm component,
      partitioning the initial total norm of the perturbation, can then be considered
      quantitatively. To demonstrate the utility of this framework, we consider an
      idealized problem, the (linear) nonmodal stability analysis of a mean flow given
      by a "Reynolds averaging" of the one-dimensional stochastically forced Burgers
      equation. We close the mean flow equation by introducing a turbulent viscosity to
      model the turbulent mixing, which we allow to evolve subject to a new transport
      equation. Since we are interested in optimizing the relative amplification of the
      perturbation kinetic energy (i.e., the perturbation's "gain") this problem
      naturally requires the use of our new framework, as the kinetic energy is a
      seminorm of the full state velocity-viscosity vector, with a new adjustable
      parameter, describing the ratio of an appropriate viscosity seminorm to the sum
      of this viscosity seminorm and the kinetic energy seminorm. Using this framework,
      we demonstrate that the dynamics of the full system, allowing the turbulent
      viscosity to evolve subject to its transport equation, is qualitatively different
      from the behavior when the turbulent viscosity is "frozen" at a fixed, mean
      value, since a new mechanism of perturbation energy production appears, through
      the coupling of the evolving turbulent viscosity perturbation and the mean
      velocity field.

PMID- 23005854
TI  - Interaction of a spark-generated bubble with a rubber beam: numerical and
      experimental study.
AB  - In this paper, the physical behaviors of the interaction between a spark
      generated bubble and a rubber beam are studied. Both numerical and experimental
      approaches are employed to investigate the bubble collapse near the rubber beam
      (which acts as a flexible boundary) and the corresponding large deformation of
      the beam. Good agreement between the numerical simulations and experimental
      observations is achieved. The analysis reveals that the ratio of the bubble-beam
      distance to the maximum bubble radius influences the bubble evolution (from
      expansion to collapse) and the beam deformation. The stiffness of the beam plays
      an important role in the elastic beam response to bubble expansion and collapse.
      The effect of the vapor pressure on both bubble collapses and beam deflections is
      also examined. The results from this paper may provide physical insight into the
      complex physics of the bubble-rubber interaction. The understanding is possibly
      applicable in biomedicine for drug delivery to tissue, which is a soft material.
      It is also probably useful in the marine industry where ultrasonic bubbles are
      generated for the defouling of ship surfaces, which has been coated with an
      elastic material. There is also potential interest in underwater explosions near
      elastic structures.

PMID- 23005855
TI  - Droplet formation in microfluidic T-junction generators operating in the
      transitional regime. III. Dynamic surfactant effects.
AB  - This study extends our previous work on droplet generation in microfluidic T
      junction generators to include dynamic interfacial tension effects created by the
      presence of surfactants. In Paper I [T. Glawdel, C. Elbuken, and C. L. Ren, Phys.
      Rev. E 85, 016322 (2012)], we presented experimental findings regarding the
      formation process in the squeezing-to-transition regime, and in Paper II [T.
      Glawdel, C. Elbuken, and C. L. Ren, Phys. Rev. E 85, 016323 (2012)] we developed
      a theoretical model that describes the performance of T-junction generators
      without surfactants. Here we study dynamic interfacial tension effects for two
      surfactants, one with a small molecular weight that adsorbs quickly, and the
      other with a large molecular weight that adsorbs slowly. Using the force balance
      developed in Paper II we extract the dynamic interfacial tension from high speed
      videos obtained during experiments. We then develop a theoretical model to
      predict the dynamic interfacial tension in microfluidic T-junction generators as
      a function of the surfactant properties, flow conditions, and generator design.
      This model is then incorporated into the overall model for generator performance
      to effectively predict the size of droplets produced when surfactants are
      present.

PMID- 23005856
TI  - Large-scale length that determines the mean rate of energy dissipation in
      turbulence.
AB  - The mean rate of energy dissipation [epsilon] per unit mass of turbulence is
      often written in the form of [epsilon]=C(u)[u(2)](3/2)/L(u), where the root-mean
      square velocity fluctuation [u(2)](1/2) and the velocity correlation length L(u)
      are parameters of the energy-containing large scales. However, the dimensionless
      coefficient C(u) is known to depend on the flow configuration that is to induce
      the turbulence. We define the correlation length L(u(2)) of the local energy
      u(2), study C(u(2))=[epsilon]L(u(2))/[u(2)](3/2) with experimental data of
      several flows, and find that C(u(2)) does not depend on the flow configuration.
      Not L(u) but L(u(2)) could serve universally as the typical size of the energy
      containing eddies, so that [u(2)](3/2)/L(u(2)) is proportional to the rate at
      which the kinetic energy is removed from those eddies and is eventually
      dissipated into heat. The independence from the flow configuration is also found
      for the two-point correlations and so on when L(u(2)) is used to normalize the
      scale.

PMID- 23005857
TI  - Drying in porous media with gravity-stabilized fronts: experimental results.
AB  - In a recent paper [Yiotis et al., Phys. Rev. E 85, 046308 (2012)] we developed a
      model for the drying of porous media in the presence of gravity. It incorporated
      effects of corner film flow, internal and external mass transfer, and the effect
      of gravity. Analytical results were derived when gravity opposes drying and hence
      leads to a stable percolation drying front. In this paper, we test the theory
      using laboratory experiments. A series of isothermal drying experiments in glass
      bead packings saturated with volatile hydrocarbons is conducted. The transparent
      glass cells containing the packing allow for the visual monitoring of the phase
      distribution patterns below the surface, including the formation of liquid films,
      as the gaseous phase invades the pore space, and for the control of the thickness
      of the diffusive mass boundary layer over the packing. The experimental results
      agree very well with theory, provided that the latter is generalized to account
      for the effects of corner roundness in the film region (which was neglected in
      the theoretical part). We demonstrate the existence of an early constant rate
      period (CRP), which lasts as long as the films saturate the surface of the
      packing, and of a subsequent falling rate period (FRP), which begins practically
      after the detachment of the film tips from the external surface. During the CRP,
      the process is controlled by diffusion within the stagnant gaseous phase in the
      upper part of the cells, yielding a Stefan tube problem solution. During the FRP,
      the process is controlled by diffusion within the packing, with a drying rate
      inversely proportional to the observed position of the film tips in the cell.
      Theoretical and experimental results compare favorably for a specific value of
      the roundness of the films, which is found to be constant and equal to 0.2 for
      various conditions, and verify the theoretical dependence on the capillary Ca(f),
      Bond Bo, and Sherwood Sh numbers.

PMID- 23005858
TI  - Dynamics of dense granular flows of small-and-large-grain mixtures in an ambient
      fluid.
AB  - Dense grain flows in nature consist of a mixture of solid constituents that are
      immersed in an ambient fluid. In order to obtain a good representation of these
      flows, the interaction mechanisms between the different constituents of the
      mixture should be considered. In this article, we study the dynamics of a dense
      granular flow composed of a binary mixture of small and large grains immersed in
      an ambient fluid. In this context, we extend the two-phase approach proposed by
      Meruane et al. [J. Fluid Mech. 648, 381 (2010)] to the case of flowing dense
      binary mixtures of solid particles, by including in the momentum equations a
      constitutive relation that describes the interaction mechanisms between the solid
      constituents in a dense regime. These coupled equations are solved numerically
      and validated by comparing the numerical results with experimental measurements
      of the front speed of gravitational granular flows resulting from the collapse,
      in ambient air or water, of two-dimensional granular columns that consisted of
      mixtures of small and large spherical particles of equal mass density. Our
      results suggest that the model equations include the essential features that
      describe the dynamics of grains flows of binary mixtures in an ambient fluid. In
      particular, it is shown that segregation of small and large grains can increase
      the front speed because of the volumetric expansion of the flow. This increase in
      flow speed is damped by the interaction forces with the ambient fluid, and this
      behavior is more pronounced in water than in air.

PMID- 23005859
TI  - Percolation and permeability of fracture networks in excavated damaged zones.
AB  - Generally, the excavation process of a gallery generates fractures in its
      immediate vicinity. The corresponding zone which is called the excavated damaged
      zone (EDZ), has a larger permeability than the intact surrounding medium.
      Therefore, some of its properties are of crucial importance for applications such
      as the storage of nuclear wastes. Field observations suggest that the fracture
      density is an exponentially decreasing function of the distance to the wall and
      that the fracture orientation is anisotropic and well approximated by a Fisher
      law whose pole is orthogonal to the wall. Numerical samples are generated
      according to these prescriptions and their percolation status and hydraulic
      transmissivity are systematically determined for a wide range of decay lengths
      and anisotropy parameters. All the numerical data are presented and discussed. A
      heuristic analytical expression for the percolation threshold is proposed which
      unifies and accurately represents all the numerical data. A simple parallel flow
      model yields an explicit analytical expression for the transmissivity as a
      function of the density, heterogeneity, and anisotropy parameters; the model also
      successfully accounts for all the numerical data.

PMID- 23005860
TI  - Lamination and mixing in three fundamental flow sequences driven by
      electromagnetic body forces.
AB  - This article pursues the idea that the degree of striations, called lamination,
      could be engineered to complement stretching and to design new sequential mixers.
      It explores lamination and mixing in three new mixing sequences experimentally
      driven by electromagnetic body forces. To generate these three mixing sequences,
      Lorentz body forces are dynamically controlled to vary the flow geometry produced
      by a pair of local jets. The first two sequences are inspired from the "tendril
      and whorl" and "blinking vortex" flows. The third novel sequence is called the
      "cat's eyes flip." These three mixing sequences exponentially stretch and
      laminate material lines representing the interface between two domains to be
      mixed. Moreover, the mixing coefficient (defined as 1-sigma(2)/sigma(0)(2) where
      sigma(2)/sigma(0)(2) is the rescaled variance) and its rate grow exponentially
      before saturation. This saturation of the mixing process is related to the
      departure of the mixing rate from an exponential growth when the striations'
      thicknesses reach the diffusive length scale of the measurements or species and
      dyes. Incidentally, in our experiments, for the same energy or forcing input, the
      cat's eyes flip sequence has higher lamination, stretching, and mixing rates than
      the tendril and whorl and the blinking vortex sequences. These features show that
      bakerlike in situ mixers can be conceived by dynamically controlling a pair of
      local jets and by integrating lamination during stirring stages with persistent
      geometries. Combined with novel insights provided by the quantification of the
      lamination, this paper should offer perspectives for the development of new
      sequential mixers, possibly on all scales.

PMID- 23005861
TI  - Lubrication of textured surfaces: a general theory for flow and shear stress
      factors.
AB  - We report on a mean field theory of textured surface lubrication. We study the
      fluid flow dynamics occurring at the interface as a function of the texture
      characteristics, e.g. texture area density, shape and distribution of
      microstructures, and local slip lengths. The present results may be very
      important for the investigation of tailored microtextured surfaces for low
      friction hydrodynamic applications.

PMID- 23005862
TI  - Boundary layer analysis in turbulent Rayleigh-Benard convection in air:
      experiment versus simulation.
AB  - We report measurements and numerical simulations of the three-dimensional
      velocity and temperature fields in turbulent Rayleigh-Benard convection in air.
      Highly resolved velocity and temperature measurements inside and outside the
      boundary layers have been directly compared with equivalent data obtained in
      direct numerical simulations (DNSs). This comparison comprises a set of two
      Rayleigh numbers at Ra=3*10(9) and 3*10(10) and a fixed aspect ratio; this is the
      ratio between the diameter and the height of the Rayleigh-Benard cell of Gamma=1.
      We find that the measured velocity data are in excellent agreement with the DNS
      results while the temperature data slightly differ. In particular, the measured
      mean temperature profile does not show the linear trend as seen in the DNS data,
      and the measured gradients at the wall are significantly higher than those
      obtained from the DNS. Both viscous and thermal boundary layer thickness scale
      with respect to the Rayleigh number as delta(v)~Ra(-0.24) and delta(theta)~Ra(
      0.24), respectively.

PMID- 23005863
TI  - Features of the dielectric permittivity of the Coulomb system and the true
      dielectric state.
AB  - Based on the linear response theory and the diagram technique of the perturbation
      theory, the correlation between the homogeneous and isotropic Coulomb system
      permittivity features caused by the nonzero static conductivity and the effects
      of external electrostatic field screening is determined. The results obtained can
      be used to study the metal-dielectric transition at zero temperature beyond the
      scope of the adiabatic approximation for nuclei. It is shown that at the critical
      point the matter consisting of electrons and nuclei of the same type is in the
      "true" dielectric state characterized by the zero static conductivity and the
      absence of screening of the weak electrostatic field.

PMID- 23005864
TI  - Coupled beam hose and self-modulation instabilities in overdense plasma.
AB  - Transverse stability of the drive beam is critical to plasma wakefield
      accelerators. A long, relativistic particle beam propagating in an overdense
      plasma is subject to beam envelope modulation and centroid displacement (hosing)
      instabilities. Coupled equations for the beam centroid and envelope are derived
      and solved. It is shown that the hosing growth rate is comparable to self
      modulation, and coupling of the self-modulation enhances beam hosing and induces
      harmonic content. Large amounts of hosing significantly alters the structure of
      the plasma wakefields.

PMID- 23005865
TI  - Thin-foil expansion into a vacuum with a two-temperature electron distribution
      function.
AB  - A kinetic theory of the expansion into a vacuum of a plasma thin foil with
      initially a hot and a cold Maxwellian electron population is examined with a one
      dimensional kinetic code. Whereas hot electrons always lose energy to expanding
      ions, cold electrons can either gain or lose energy depending on the initial
      temperature and density ratios and on time. When the cold electrons' density is
      not too large, they experience initially an adiabatic compression by the electric
      field associated with the rarefaction wave. The corresponding temperature
      increase can be as large as a factor of a few tens. Later on, as expected, the
      cold electrons eventually lose energy to the expansion. When cold electrons are
      numerically dominant, a rarefaction shock appears during the first phase of the
      expansion. Hot electrons cool down faster than cold electrons, thus reducing the
      effective temperature ratio. Furthermore, the amplitude of the rarefaction shock
      and the dip that it causes on the ion velocity spectrum tend to be smoothed out
      by the expansion.

PMID- 23005866
TI  - Time dependence of fast electron beam divergence in ultraintense laser-plasma
      interactions.
AB  - We report on the measurement and computer simulation of the divergence of fast
      electrons generated in an ultraintense laser-plasma interaction (LPI) and the
      subsequent propagation in a nonrefluxing target. We show that, at Ilambda(2) of
      10(20) Wcm(-2)MUm(2), the time-integrated electron beam full divergence angle is
      (60+/-5) degrees . However, our time-resolved 2D particle-in-cell simulations
      show the initial beam divergence to be much smaller (<=30 degrees ). Our
      simulations show the divergence to monotonically increase with time, reaching a
      final value of (68+/-7) degrees  after the passage of the laser pulse, consistent
      with the experimental time-integrated measurements. By revealing the time
      dependent nature of the LPI, we find that a substantial fraction of the laser
      energy (~7%) is transported up to 100 MUm with a divergence of 32 degrees .

PMID- 23005867
TI  - Plastic ablator and hydrodynamic instabilities: a first-principles set of
      microscopic coefficients.
AB  - We have performed orbital-free and quantum molecular dynamics simulations on
      plastic ablator along two isochores, namely 7 and 9 g cm(-3), from 5 to 40 eV.
      These thermodynamic conditions correspond to those encountered during inertial
      confinement fusion capsule implosion when hydrodynamic instabilities can take
      place. The coupling between orbital-free and quantum approaches allowed us to
      compute an exhaustive set of microscopic coefficients, i.e., equation-of-state,
      ionic diffusion coefficients, thermal and electrical conductivities, spanning
      phenomena that can mitigate the growth of classical Rayleigh-Taylor instability.
      Comparisons to widely used models in hydrodynamics codes are developed.

PMID- 23005868
TI  - Energy transport in short-pulse-laser-heated targets measured using extreme
      ultraviolet laser backlighting.
AB  - The accurate characterization of thermal electron transport and the determination
      of heating by suprathermal electrons in laser driven solid targets are both
      issues of great importance to the current experiments being performed at the
      National Ignition Facility, which aims to achieve thermonuclear fusion ignition
      using lasers. Ionization, induced by electronic heat conduction, can cause the
      opacity of a material to drop significantly once bound-free photoionization is no
      longer energetically possible. We show that this drop in opacity enables
      measurements of the transmission of extreme ultraviolet (EUV) laser pulses at
      13.9 nm to act as a signature of the heating of thin (50 nm) iron layers with a
      50-nm thick parylene-N (CH) overlay irradiated by 35-fs pulses at irradiance
      3*10(16) Wcm(-2). Comparing EUV transmission measurements at different times
      after irradiation to fluid code simulations shows that the target is
      instantaneously heated by hot electrons (with approximately 10% of the laser
      energy), followed by thermal conduction with a flux limiter of ~0.05.

PMID- 23005869
TI  - Plasma effects on harmonic spectra generated from moderately relativistic laser
      plasma interactions.
AB  - When intense p-polarized laser light is incident on a plasma with an electron
      density many times the critical density, the flux of fast electrons created by
      Brunel absorption excites plasma oscillations. These oscillations may in turn
      affect the spectrum of high harmonics by modulating the spectrum at the plasma
      frequency, omega(p), and by coupling to the radiation field through the steep
      density gradient at the plasma-vacuum interface, so generating plasma line
      emission (PLE) at omega(p) and harmonics of omega(p). Both aspects depend
      sensitively on a range of plasma and laser pulse parameters, including the
      initial electron density, the density profile at the plasma-vacuum interface, and
      the intensity, pulse shape, and pulse length of the incident laser light. These
      various dependences have been characterised for moderately relativistic laser
      plasma interactions by means of a series of particle-in-cell (PIC) simulations.

PMID- 23005870
TI  - Periodic orbits of inelastic particles on a ring.
AB  - We consider the dynamics of N rigid particles of arbitrary mass that are
      constrained to move on a frictionless ring. Collisions between particles are
      inelastic with a constant coefficient of restitution e, and between collisions
      the particles move with constant velocity. We study sequences of collisions that
      are self-similar in the sense that the relative positions return to their
      original relative positions after the collision sequence while the relative
      velocities are reduced by a constant factor. For a given collision sequence, we
      develop the analytic machinery to determine the particle velocities and the
      locations of collisions, and we show that the problem of determining self-similar
      orbits reduces to solving an eigenvalue problem to obtain the particle velocities
      and solving a linear system to obtain the locations of interparticle collisions.
      For inelastic systems, we show that the collision locations can always be
      uniquely determined. We also show that this is in sharp contrast to the case of
      elastic systems in which infinite families of self-similar orbits can coexist.

PMID- 23005871
TI  - Theoretical analyses of multiple quasi-phase-matched third-harmonic generation
      for all configurations.
AB  - A general theory for multiple quasi-phase-matched third-harmonic generation is
      investigated systematically. We find that there are up to 24 configurations for
      third-harmonic generation by cascaded two-parametric processes. All these
      configurations can be divided into three categories based on the coupling types
      of the harmonic fields. Each category has a set of coupled wave equations that
      describe its characteristics. The analytical solutions reveal some features, such
      as the polarization tuning and quasi-phase-matched gap effect.

PMID- 23005872
TI  - Nonlinear amplification of coherent waves in media with soliton-type refractive
      index pattern.
AB  - We derive the complex Ginzburg-Landau equation for the dynamical self-diffraction
      of optical waves in a nonlinear cavity. The case of the reflection geometry of
      wave interaction as well as a medium that possesses the cubic nonlinearity
      (including a local and a nonlocal nonlinear responses) and the relaxation is
      considered. A stable localized spatial structure in the form of a "dark"
      dissipative soliton is formed in the cavity in the steady state. The envelope of
      the intensity pattern, as well as of the dynamical grating amplitude, takes the
      shape of a tanh function. The obtained complex Ginzburg-Landau equation describes
      the dynamics of this envelope; at the same time, the evolution of this spatial
      structure changes the parameters of the output waves. New effects are predicted
      in this system due to the transformation of the dissipative soliton which takes
      place during the interaction of a pulse with a continuous wave, such as retention
      of the pulse shape during the transmission of impulses in a long nonlinear
      cavity, and giant amplification of a seed pulse, which takes energy due to
      redistribution of the pump continuous energy into the signal.

PMID- 23005873
TI  - Asymmetric ac fluxon depinning in a Josephson junction array: a highly discrete
      limit.
AB  - Directed motion and depinning of topological solitons in a strongly discrete
      damped and biharmonically ac-driven array of Josephson junctions is studied. The
      mechanism of the depinning transition is investigated in detail. We show that the
      depinning process takes place through chaotization of an initially standing
      fluxon periodic orbit. Detailed investigation of the Floquet multipliers of these
      orbits shows that, depending on the depinning parameters (either the driving
      amplitude or the phase shift between harmonics), the chaotization process can
      take place either along the period-doubling scenario or due to the type I
      intermittency.

PMID- 23005874
TI  - Wide localized solitons in systems with time- and space-modulated nonlinearities.
AB  - In this work we apply point canonical transformations to solve some classes of
      nonautonomous, nonlinear Schrodinger equations, namely, those which possess
      specific cubic and quintic (time- and space-dependent) nonlinearities. In this
      way we generalize some procedures recently published which resort to an ansatz to
      the wave function and recover a time- and space-independent nonlinear equation
      which can be solved explicitly. The method applied here allows us to find wide
      localized (in space) soliton solutions to the nonautonomous, nonlinear
      Schrodinger equation. We also generalize the external potential which traps the
      system and the terms of the nonlinearities.

PMID- 23005875
TI  - Sasa-Satsuma equation: soliton on a background and its limiting cases.
AB  - We present a multiparameter family of a soliton on a background solution to the
      Sasa-Satsuma equation. The solution is controlled by a set of several free
      parameters that control the background amplitude as well as the soliton itself.
      This family of solutions admits a few nontrivial limiting cases that are
      considered in detail. Among these special cases is the nonlinear Schrodinger
      equation limit and the limit of rogue wave solutions.

PMID- 23005876
TI  - Mass and momentum transfer across solid-fluid boundaries in the lattice-Boltzmann
      method.
AB  - Mass conservation and momentum transfer across solid-fluid boundaries have been
      active topics through the development of the lattice-Boltzmann method. In this
      paper, we review typical treatments to prevent net mass transfer across solid
      fluid boundaries in the lattice-Boltzmann method, and argue that such efforts are
      in general not necessary and could lead to incorrect results. Carefully designed
      simulations are conducted to examine the effects of normal boundary movement,
      tangential density gradient, and lattice grid resolution. Our simulation results
      show that the global mass conservation can be well satisfied even with local
      unbalanced mass transfer at boundary nodes, while a local mass conservation
      constraint can produce incorrect flow and pressure fields. These simulations
      suggest that local mass conservation, at either a fluid or solid boundary node,
      is not only an unnecessary consequence to maintain the global mass conservation,
      but also harmful for meaningful simulation results. In addition, the concern on
      the momentum addition and reduction associated with status-changing nodes is also
      not technically necessary. Although including this momentum addition or reduction
      has no direct influence on flow and pressure fields, the incorrect fluid-particle
      interaction may affect simulation results of particulate suspensions.

PMID- 23005877
TI  - Extended Kramers-Moyal analysis applied to optical trapping.
AB  - The Kramers-Moyal analysis is a well-established approach to analyze stochastic
      time series from complex systems. If the sampling interval of a measured time
      series is too low, systematic errors occur in the analysis results. These errors
      are labeled as finite time effects in the literature. In the present article, we
      present some new insights about these effects and discuss the limitations of a
      previously published method to estimate Kramers-Moyal coefficients at the
      presence of finite time effects. To increase the reliability of this method and
      to avoid misinterpretations, we extend it by the computation of error estimates
      for estimated parameters using a Monte Carlo error propagation technique.
      Finally, the extended method is applied to a data set of an optical trapping
      experiment yielding estimations of the forces acting on a Brownian particle
      trapped by optical tweezers. We find an increased Markov-Einstein time scale of
      the order of the relaxation time of the process, which can be traced back to
      memory effects caused by the interaction of the particle and the fluid. Above the
      Markov-Einstein time scale, the process can be very well described by the
      classical overdamped Markov model for Brownian motion.

PMID- 23005878
TI  - Locally disrupted synchronization in Langevin molecular dynamics.
AB  - Stochastic thermostats commonly used in molecular dynamics trajectories are
      known, under certain conditions, to exhibit a synchronization effect whereby
      trajectories initialized at different points in phase space synchronize to a
      single master trajectory if they are subjected to the same sequence of random
      forces. We investigate the spatiotemporal robustness of this effect analytically
      and with molecular dynamics simulations in one and three dimensions in the strong
      coupling limit. We first investigate the response of the system to a time- and
      spacewise local perturbation and show that desynchronization behaves diffusively
      at long times for infinite systems. We then explore the behavior of temporally
      persistent but spatially local perturbations and observe strikingly different
      behaviors as a function of dimensionality: in one dimension, the
      desynchronization propagates through the whole lattice and grows with time, while
      in three dimensions, the desynchronization remains localized in the neighborhood
      of the perturbation.

PMID- 23005879
TI  - Error estimate of short-range force calculation in inhomogeneous molecular
      systems.
AB  - In the present paper, we develop an accurate error estimate of the nonbonded
      short-range interactions for the inhomogeneous molecular systems. The root-mean
      square force error is proved to be decomposed into three additive parts: the
      homogeneity error, the inhomogeneity error, and the correlation error. The
      magnitude of the inhomogeneity error, which is dominant in the interfacial
      regions, can be more than one order of magnitude larger than the homogeneity
      error. This is the reason why a standard simulation with fixed cutoff radius is
      either less accurate if the cutoff is too small, or wastes considerable
      computational effort if the cutoff is too large. Therefore, based on the error
      estimate, the adaptive cutoff and long-range force correction methods are
      proposed to boost the efficiency and accuracy of the simulation, respectively.
      The way of correcting the long-range contribution of pressure is also developed
      for the inhomogeneous system. The effectiveness of the proposed methods is
      demonstrated by molecular dynamics simulations of the liquid-vapor equilibrium
      and the nanoscale particle collision. Different roles of the homogeneity error
      and inhomogeneity error are also discussed.

PMID- 23005880
TI  - Lagrange-mesh calculations in momentum space.
AB  - The Lagrange-mesh method is a powerful method to solve eigenequations written in
      configuration space. It is very easy to implement and very accurate. Using a
      Gauss quadrature rule, the method requires only the evaluation of the potential
      at some mesh points. The eigenfunctions are expanded in terms of regularized
      Lagrange functions which vanish at all mesh points except one. It is shown that
      this method can be adapted to solve eigenequations written in momentum space,
      keeping the convenience and the accuracy of the original technique. In
      particular, the kinetic operator is a diagonal matrix. Observables and wave
      functions in both configuration space and momentum space can also be easily
      computed with good accuracy using only eigenfunctions computed in the momentum
      space. The method is tested with Gaussian and Yukawa potentials, requiring,
      respectively, a small and a large mesh to reach convergence. Corresponding wave
      functions in both spaces are compared with each other using the Fourier
      transform.

PMID- 23005881
TI  - Performance of a cavity-method-based algorithm for the prize-collecting Steiner
      tree problem on graphs.
AB  - We study the behavior of an algorithm derived from the cavity method for the
      prize-collecting steiner tree (PCST) problem on graphs. The algorithm is based on
      the zero temperature limit of the cavity equations and as such is formally simple
      (a fixed point equation resolved by iteration) and distributed (parallelizable).
      We provide a detailed comparison with state-of-the-art algorithms on a wide range
      of existing benchmarks, networks, and random graphs. Specifically, we consider an
      enhanced derivative of the Goemans-Williamson heuristics and the dhea solver, a
      branch and cut integer linear programming based approach. The comparison shows
      that the cavity algorithm outperforms the two algorithms in most large instances
      both in running time and quality of the solution. Finally we prove a few
      optimality properties of the solutions provided by our algorithm, including
      optimality under the two postprocessing procedures defined in the Goemans
      Williamson derivative and global optimality in some limit cases.

PMID- 23005882
TI  - Local-gauge finite-element method for electron waves in magnetic fields.
AB  - The finite-element method (FEM) has already been extended to analyze transport
      properties of electron waves of two-dimensional electron systems in magnetic
      fields. Although many researchers have created new formulations or improvements
      to this method, few have analyzed how this method is applied to realistic
      systems. The present paper suggests that conventional formulations of the FEM do
      not give accurate results for large systems or for strong magnetic fields; in
      addition, it suggests that the selected gauge significantly influences the
      numerical results. Furthermore, this paper proposes a conceptually different
      formulation of the FEM that solves the poor convergence problem. This formulation
      is simple: matrix elements are multiplied by the Peierls phase in the absence of
      a magnetic field. To show the advantages of this formulation, numerical examples
      are presented.

PMID- 23005883
TI  - Coarse-grained lattice Monte Carlo simulations with continuous interaction
      potentials.
AB  - A coarse-grained lattice Metropolis Monte Carlo (CG-MMC) method is presented for
      simulating fluid systems described by standard molecular force fields. First, a
      thermodynamically consistent coarse-grained interaction potential is obtained
      numerically and automatically from a continuous force field such as Lennard
      Jones. The coarse-grained potential then is used to drive CG-MMC simulations of
      vapor-liquid equilibrium in Lennard-Jones, square-well, and simple point charge
      water systems. The CG-MMC predicts vapor-liquid phase envelopes, as well as the
      particle density distributions in both the liquid and vapor phases, in excellent
      agreement with full-resolution Monte Carlo simulations, at a fraction of the
      computational cost.

PMID- 23005884
TI  - Event-driven Langevin simulations of hard spheres.
AB  - The blossoming of interest in colloids and nanoparticles has given renewed
      impulse to the study of hard-body systems. In particular, hard spheres have
      become a real test system for theories and experiments. It is therefore necessary
      to study the complex dynamics of such systems in presence of a solvent;
      disregarding hydrodynamic interactions, the simplest model is the Langevin
      equation. Unfortunately, standard algorithms for the numerical integration of the
      Langevin equation require that interactions are slowly varying during an
      integration time step. This is not the case for hard-body systems, where there is
      no clear-cut distinction between the correlation time of the noise and the time
      scale of the interactions. Starting first from a splitting of the Fokker-Plank
      operator associated with the Langevin dynamics, and then from an approximation of
      the two-body Green's function, we introduce and test two algorithms for the
      simulation of the Langevin dynamics of hard spheres.

PMID- 23005885
TI  - Normal contact stiffness of elastic solids with fractal rough surfaces for one-
      and three-dimensional systems.
AB  - It was shown earlier that some classes of three-dimensional contact problems can
      be mapped onto one-dimensional systems without loss of essential macroscopic
      information, thus allowing for immense acceleration of numerical simulations. The
      validity of this method of reduction of dimensionality has been strictly proven
      for contact of any axisymmetric bodies, both with and without adhesion. In [T.
      Geike and V. L. Popov, Phys. Rev. E 76, 036710 (2007)], it was shown that this
      method is valid "with empirical accuracy" for the simulation of contacts between
      randomly rough surfaces. In the present paper, we compare exact calculations of
      contact stiffness between elastic bodies with fractal rough surfaces (carried out
      by means of the boundary element method) with results of the corresponding one
      dimensional model. Both calculations independently predict the contact stiffness
      as a function of the applied normal force to be a power law, with the exponent
      varying from 0.50 to 0.85, depending on the fractal dimension. The results
      strongly support the application of the method of reduction of dimensionality to
      a general class of randomly rough surfaces. The mapping onto a one-dimensional
      system drastically decreases the computation time.

PMID- 23005886
TI  - Asymptotic response of observables from divergent weak-coupling expansions: a
      fractional-calculus-assisted Pade technique.
AB  - Appropriate constructions of Pade approximants are believed to provide reasonable
      estimates of the asymptotic (large-coupling) amplitude and exponent of an
      observable, given its weak-coupling expansion to some desired order. In many
      instances, however, sequences of such approximants are seen to converge very
      poorly. We outline here a strategy that exploits the idea of fractional calculus
      to considerably improve the convergence behavior. Pilot calculations on the
      ground-state perturbative energy series of quartic, sextic, and octic anharmonic
      oscillators reveal clearly the worth of our endeavor.

PMID- 23005887
TI  - Structural susceptibility and separation of time scales in the van der Pol
      oscillator.
AB  - We use an extension of the van der Pol oscillator as an example of a system with
      multiple time scales to study the susceptibility of its trajectory to polynomial
      perturbations in the dynamics. A striking feature of many nonlinear,
      multiparameter models is an apparently inherent insensitivity to large-magnitude
      variations in certain linear combinations of parameters. This phenomenon of
      "sloppiness" is quantified by calculating the eigenvalues of the Hessian matrix
      of the least-squares cost function. These typically span many orders of
      magnitude. The van der Pol system is no exception: Perturbations in its dynamics
      show that most directions in parameter space weakly affect the limit cycle,
      whereas only a few directions are stiff. With this study, we show that separating
      the time scales in the van der Pol system leads to a further separation of
      eigenvalues. Parameter combinations which perturb the slow manifold are stiffer
      and those which solely affect the jumps in the dynamics are sloppier.

PMID- 23005888
TI  - Branching process approach for Boolean bipartite networks of metabolic reactions.
AB  - The branching process (BP) approach has been successful in explaining the
      avalanche dynamics in complex networks. However, its applications are mainly
      focused on unipartite networks, in which all nodes are of the same type. Here,
      motivated by a need to understand avalanche dynamics in metabolic networks, we
      extend the BP approach to a particular bipartite network composed of Boolean AND
      and OR logic gates. We reduce the bipartite network into a unipartite network by
      integrating out OR gates and obtain the effective branching ratio for the
      remaining AND gates. Then the standard BP approach is applied to the reduced
      network, and the avalanche-size distribution is obtained. We test the BP results
      with simulations on the model networks and two microbial metabolic networks,
      demonstrating the usefulness of the BP approach.

PMID- 23005889
TI  - Onset of chaotic phase synchronization in complex networks of coupled
      heterogeneous oscillators.
AB  - Existing studies on network synchronization focused on complex networks
      possessing either identical or nonidentical but simple nodal dynamics. We
      consider networks of both complex topologies and heterogeneous but chaotic
      oscillators, and investigate the onset of global phase synchronization. Based on
      a heuristic analysis and by developing an efficient numerical procedure to detect
      the onset of phase synchronization, we uncover a general scaling law, revealing
      that chaotic phase synchronization can be facilitated by making the network more
      densely connected. Our methodology can find applications in probing the
      fundamental network dynamics in realistic situations, where both complex topology
      and complicated, heterogeneous nodal dynamics are expected.

PMID- 23005890
TI  - Effect of the Rayleigh-Taylor instability on maximum reachable temperatures in
      laser-induced bubbles.
AB  - Laser-induced bubbles provide an effective vehicle to achieve high-energy
      concentrations and maximum temperatures in bubble luminescence phenomena. One
      limitation to the temperatures that can be achieved is the development of the
      Rayleigh-Taylor instability (RTI) during the instants previous to the bubble
      maximum compression. For a given fluid, the control parameters of the experiment
      are: the bubble maximum radius, the bubble ambient radius, the initial
      perturbations of the bubble, and the liquid pressure at infinity. In this work,
      experiments using laser-induced bubbles in a highly viscous phosphoric acid were
      performed in order to determine the achievable parameters values in the phase
      space. The effect of R(max), R(0), a(2)(i), a(3)(i), and p(infinity) on the
      maximum temperature achieved by the gas contents inside the bubble were
      numerically determined. The results show for each static pressure an optimum
      region for maximum temperatures of the gas contents bounded by the RTI.

PMID- 23005891
TI  - Parametric decay of oblique Alfven waves in two-dimensional hybrid simulations.
AB  - Certain types of plasma waves are known to become parametrically unstable under
      specific plasma conditions, in which the pump wave will decay into several
      daughter waves with different wavenumbers and frequencies. In the past, the
      related plasma instabilities have been treated analytically for various parameter
      regimes and by use of various numerical methods, yet the oblique propagation with
      respect to the background magnetic field has rarely been dealt with in two
      dimensions, mainly because of the high computational demand. Here we present a
      hybrid-simulation study of the parametric decay of a moderately oblique Alfven
      wave having elliptical polarization. It is found that such a compressive wave can
      decay into waves with higher and lower wavenumbers than the pump.

PMID- 23005892
TI  - Modulation of localized solutions in a system of two coupled nonlinear
      Schrodinger equations.
AB  - In this work we study localized solutions of a system of two coupled nonlinear
      Schrodinger equations, with the linear (potential) and nonlinear coefficients
      engendering spatial and temporal dependencies. Similarity transformations are
      used to convert the nonautonomous coupled equations into autonomous ones and we
      use the trial orbit method to help us solving them, presenting solutions in a
      general way. Numerical experiments are then used to verify the stability of the
      localized solutions.

PMID- 23005893
TI  - Molecular view of phase coexistence in lipid monolayers.
AB  - We used computer simulations to study the effect of phase separation on the
      properties of lipid monolayers. This is important for understanding the lipid
      lipid interactions underlying lateral heterogeneity (rafts) in biological
      membranes and the role of domains in the regulation of surface tension by lung
      surfactant. Molecular dynamics simulations with the coarse-grained MARTINI force
      field were employed to model large length (~80 nm in lateral dimension) and time
      (tens of microseconds) scales. Lipid mixtures containing saturated and
      unsaturated lipids and cholesterol were investigated under varying surface
      tension and temperature. We reproduced compositional lipid demixing and the
      coexistence of liquid-expanded and liquid-condensed phases as well as liquid
      ordered and liquid-disordered phases. Formation of the more ordered phase was
      induced by lowering the surface tension or temperature. Phase transformations
      occurred via either nucleation or spinodal decomposition. In nucleation, multiple
      domains formed initially and subsequently merged. Using cluster analysis combined
      with Voronoi tessellation, we characterized the partial areas of the lipids in
      each phase, the phase composition, the boundary length, and the line tension
      under varying surface tension. We calculated the growth exponents for nucleation
      and spinodal decomposition using a dynamical scaling hypothesis. At low surface
      tensions, liquid-ordered domains manifest spontaneous curvature. Lateral
      diffusion of lipids is significantly slower in the more ordered phase, as
      expected. The presence of domains increased the monolayer surface viscosity, in
      particular as a result of domain reorganization under shear.

PMID- 23005894
TI  - An unusual cause of fever.
AB  - A 5-month old infant presented with a short history of fever of unknown origin.
      He initially appeared well although there was a resting tachycardia during
      periods of normal temperature, and pancytopenia. He remained febrile in spite of
      antibiotic therapy and by 48 h he had developed marked hepatosplenomegaly and
      coagulopathy. At 72 h a bone marrow aspirate and trephine biopsy showed
      haemophagocytosis. By this time the infant was encephalopathic and
      haemodynamically unstable with multi-organ dysfunction. Treatment with high-dose
      methylprednisolone and cyclosporin was commenced with an initial good response.
      Unfortunately the patient ultimately died of infective complications of treatment
      and reactivation of the underlying disease process. Haemophagocytic
      lymphohistiocytosis (HLH) is a rare disorder of the mononuclear phagocyte system
      characterised by proliferation of morphologically benign histiocytes resulting in
      hypercytokinaemia and uncontrolled activation of immune cells. The diagnosis of
      familial HLH should be considered in any infant with fever, splenomegaly and
      cytopenia of at least two cell lines. HLH may be cured by immunosuppressive
      therapy and eventual stem cell transplantation but rapid disease progression to
      multi-organ failure results in a high mortality.

PMID- 23005895
TI  - Bayesian latent factor regression for functional and longitudinal data.
AB  - In studies involving functional data, it is commonly of interest to model the
      impact of predictors on the distribution of the curves, allowing flexible effects
      on not only the mean curve but also the distribution about the mean.
      Characterizing the curve for each subject as a linear combination of a high
      dimensional set of potential basis functions, we place a sparse latent factor
      regression model on the basis coefficients. We induce basis selection by choosing
      a shrinkage prior that allows many of the loadings to be close to zero. The
      number of latent factors is treated as unknown through a highly-efficient,
      adaptive-blocked Gibbs sampler. Predictors are included on the latent variables
      level, while allowing different predictors to impact different latent factors.
      This model induces a framework for functional response regression in which the
      distribution of the curves is allowed to change flexibly with predictors. The
      performance is assessed through simulation studies and the methods are applied to
      data on blood pressure trajectories during pregnancy.

PMID- 23005896
TI  - Vascular endothelial growth factor (VEGF) gene polymorphisms and colorectal
      cancer: a meta-analysis of epidemiologic studies.
AB  - BACKGROUND: Studies investigating the association between vascular endothelial
      growth factor (VEGF) polymorphisms and colorectal cancer (CRC) risk report
      conflicting results. To clarify the effect of four VEGF (-460T/C, -634G/C,
      +936C/T, and -2578C/A) gene polymorphisms on the risk of developing CRC, we
      carried out a meta-analysis using published data to obtain more precise estimates
      of risk. METHODS: Electronic searches of PubMed and EMBASE were conducted to
      select studies for this meta-analysis. The principal outcome measure was the odds
      ratio (OR) with 95% confidence interval (CI) for the risk of CRC associated with
      four VEGF (-460T/C, -634G/C, +936C/T, and -2578C/A) gene polymorphisms. RESULTS:
      We identified 12 epidemiologic studies, which included 2770 CRC cases and 2568
      controls. The combined results based on all studies showed that CRC cases had a
      significantly higher frequency of VEGF -634GG (OR=1.24, 95% CI=1.06, 1.44) and 
      2578AA (OR=1.37, 95% CI=1.12, 1.66) genotype and a lower frequency of -634CG
      (OR=0.82, 95% CI=0.71, 0.95) than controls. When stratifying for race, we found
      that patients with CRC had a significantly higher frequency of -460TC (OR=1.54,
      95% CI=1.22, 1.94), -460CC (OR=2.00, 95% CI=1.50, 2.67), and -2578AA (OR=1.38,
      95% CI=1.12, 1.69) and a lower frequency of -2578AA (OR=0.78, 95% CI=0.65, 0.93)
      genotypes of VEGF than controls, among Caucasians. We also found that patients
      with CRC had a significantly higher frequency of -634GG (OR=1.61, 95% CI=1.20,
      2.15) and a lower frequency of -634CG (OR=0.60, 95% CI=0.46, 0.79) genotypes of
      VEGF than controls, among Asians. CONCLUSIONS: Our meta-analysis suggests that
      the VEGF -460T/C, -634G/C, and -2578C/A gene polymorphisms are associated with a
      risk of CRC.

PMID- 23005897
TI  - The need for 'representative task design' in evaluating efficacy of skills tests
      in sport: a comment on Russell, Benton and Kingsley (2010).
AB  - Russell, Benton and Kingsley (2010) recently suggested a new association football
      test comprising three different tasks for the evaluation of players' passing,
      dribbling and shooting skills. Their stated intention was to enhance 'ecological
      validity' of current association football skills tests allowing generalisation of
      results from the new protocols to performance constraints that were
      'representative' of experiences during competitive game situations. However, in
      this comment we raise some concerns with their use of the term 'ecological
      validity' to allude to aspects of 'representative task design'. We propose that
      in their paper the authors confused understanding of environmental properties,
      performance achievement and generalisability of the test and its outcomes. Here,
      we argue that the tests designed by Russell and colleagues did not include
      critical sources of environmental information, such as the active role of
      opponents, which players typically use to organise their actions during
      performance. Static tasks which are not representative of the competitive
      performance environment may lead to different emerging patterns of movement
      organisation and performance outcomes, failing to effectively evaluate skills
      performance in sport.

PMID- 23005898
TI  - Mechanism of "turn-on" fluorescent sensors for mercury(II) in solution and its
      implications for ligand design.
AB  - The tendency of a Hg(II) ion to strongly quench fluorescence of potential
      fluorescent sensors is explored. Fluorescence measurements show the expected
      order of the chelation-enhanced fluorescence (CHEF) effect of Zn(II) > Cd(II) >>
      Hg(II) ~ Cu(II), which is interpreted as (1) unpaired electrons causing the weak
      CHEF effect for Cu(II) and (2) the order Zn(II) > Cd(II) >> Hg(II) reflecting the
      "heavy atom" effect, which may be due to increasing spin-orbit coupling constants
      (zeta) for Zn(II) < Cd(II) << Hg(II). The structures of mercury(II) complexes of
      N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine (ADPA) are
      reported. [Hg(ADPA)Cl(2)HgCl(2)] (1) has one Hg(II) held by two bridging
      chlorides, while the other Hg(II) is coordinated to the ADPA ligand. The latter
      Hg(II) has a nearest pi contact of 3.215 A with a C atom from the anthracenyl
      group, which falls in the range of reported Hg-C pi contacts with aromatic
      groups. This contact may be important in quenching the fluorescence of the
      Hg(II)/ADPA complex. A density functional theory study shows that the Hg-C
      interaction is strong enough to prevent a simple HOMO -> LUMO transition of the
      fluorophore. In fact, the S(0) -> S(1) and S(2) transitions in the Hg(II)/ADPA
      complex have significant charge-transfer character to mercury. An important
      aspect of the coordination geometry of Hg(II) is illustrated by 1, where Hg(II)
      tends to form a few (often only two) short bonds to the more covalently binding
      donor atoms present, with much longer bonds to other donor atoms. The Hg-N bonds
      to the two pyridyl N-donor atoms of ADPA in 1 are relatively short at 2.212(8)
      and 2.224(8) A, while that to the central saturated N-donor atom of ADPA is long
      at 2.603(8) A. The latter long Hg-N bond may allow a photoinduced electron
      transfer (PET) effect, quenching the fluorescence of the anthracenyl fluorophore.
      The structure of [Hg(ADPA)Br(2)] (2) reflects the more covalent binding of the
      two bromine ligands compared to the clorine ligands of 1, with much longer Hg-C
      contacts with the anthracenyl fluorophore and a Hg-N contact with the saturated N
      atom of ADPA of 2.917 A. The latter long Hg-N contact is related to the nearly
      negligible fluorescence of the ADPA complex in the presence of added Br(-). The
      addition of extra ligands to the Hg(II)/ADPA complex produces a weak increase in
      the fluorescence intensity for OH(-) ~ Cl(-) >> Br(-) > I(-), which is discussed
      in terms of an increasing PET effect, and to collisional quenching. The ligand
      design principles for generating turn-on sensors for mercury suggested by this
      work are discussed.

PMID- 23005899
TI  - "Straight Talk" for African-American heterosexual men: results of a single-arm
      behavioral intervention trial.
AB  - In the United States, heterosexual transmission is the second leading cause of
      HIV/AIDS, and two-thirds of all heterosexually acquired cases diagnosed between
      2005 and 2008 occurred among African-Americans. Few HIV prevention interventions
      have been designed specifically for African-American heterosexual men not seeking
      clinical treatment. Here we report results of a single-arm intervention trial of
      a theory-based HIV prevention intervention designed to increase condom use,
      reduce concurrent partnering and increase HIV testing among heterosexually active
      African-American men living in high HIV prevalence areas of New York City. We
      tested our hypothesis using McNemar discordant pairs exact test for binary
      variables and paired t-tests for continuous variables. We observed statistically
      significant declines in mean number of total and new female partners, unprotected
      sex partners, and partner concurrency in both primary and nonprimary sex
      partnerships between baseline and 3 months postintervention.

PMID- 23005900
TI  - Splanchnic net balance of oxygen and metabolites in response to a discontinuous
      mesenteric vein infusion of ammonium in sheep.
AB  - To simulate daily episodes of high absorption associated with the intake of diets
      with high N content, four wethers (42 +/- 3.4 kg body weight), fitted with
      permanent catheters in the femoral artery and splanchnic vessels, were infused
      with 340 MUmol into the mesenteric vein for 3 h, during the morning meal, over
      seven consecutive days. On the 7th day, mass transfers of , urea, glucose,
      lactate, beta-OH-butyrate and O2 were measured across portal-drained viscera
      (PDV), liver and splanchnic tissues during the last 90 min of the infusion.
      Measurements were repeated on the following day, at the same time, without the
      infusion. Plasma concentration in the portal vein (+332 MUm; p = 0.006), portal
      absorption (+424 MUmol/min; p < 0.001), liver uptake (+375 MUmol/min; p = 0.003)
      and urea N production (+338 MUmol/min; p = 0.059) were higher during infusion.
      Mass transfers of urea, glucose, lactate, beta-OH-butyrate and O2 across the PDV,
      and glucose, lactate, beta-OH-butyrate and O2 across the liver, were not altered
      by the infusion. Results suggest that a daily, discontinuous increase in portal
      flow during a meal stimulates liver removal and urea N production but does not
      significantly affect liver glucose production and O2 consumption in sheep. 

PMID- 23005901
TI  - Double recurrence of group B streptococcus bacteremia in an immunocompetent
      infant.
AB  - We report an immunocompetent infantile case wherein group B streptococcus
      bacteremia recurred two times. The isolated bacteria which colonized in his
      nasopharyngeal cavity might be a source of repetitive infection. Although the
      best action has not been established yet, penicillin G as the prophylaxis seemed
      to be effective in this case.

PMID- 23005902
TI  - Rhabdomyolysis associated with influenza A/H1N1 2009 infection in a pediatric
      patient.
AB  - The influenza A/H1N1 2009 epidemic has spread to many countries since 2009,
      including Japan. We report an immune-competent child involving rhabdomyolysis and
      compartment syndrome associated with influenza A/H1N1 2009. The patient was
      demonstrated rhabdomyolysis with myoglobinuria, hyperkalemia, cardiac dysfunction
      and compartment syndrome that arose during convalescence from influenza A/H1N1
      2009 infection. Although RT-PCR of muscle tissue yielded negative results for
      influenza A/H1N1 2009 RNA and no viral positive-antigen cells were detected in
      the muscle lesions, the clinical picture suggested rhabdomyolysis associated with
      influenza A/H1N1. Rhabdomyolysis should be considered in the evaluation of muscle
      symptoms such as myalgia associated with novel influenza A/H1N1 2009 virus
      infection, particularly in critically ill patients.

PMID- 23005903
TI  - Streptococcus viridans tubo-ovarian abscess in an adolescent virgin.
AB  - A tubo-ovarian abscess (TOA) is a common complication of pelvic inflammatory
      disease in premenopausal women; however, in virginal females, TOAs are an
      exceedingly rare occurrence. Within this rare subset of patients, there is almost
      always an underlying condition, such as vaginal voiding, or a concomitant disease
      process. A virginal adolescent female with no prior medical history presented
      with a large pelvic mass which proved to be a TOA. An exploratory laparotomy was
      eventually required to establish the diagnosis. Open drainage and antibiotic
      therapy successfully treated the patient. With only the organism, Streptococcus
      viridians, isolated in her cultures, an etiology of direct ascension from the
      lower genitourinary tract is implicated. We believe this to be the youngest case
      of a TOA occurring in a virginal adolescent female without a predisposing
      condition. A TOA should be considered in the differential diagnosis of pelvic
      masses in previously healthy pediatric patients regardless of their sexual
      activity.

PMID- 23005904
TI  - Respiratory syncytial virus-associated encephalopathy complicated by congenital
      myopathy.
AB  - A 23-month-old Japanese girl with a severe form of congenital fiber type
      disproportion myopathy under mechanical ventilation suffered from respiratory
      syncytial virus (RSV) bronchiolitis, complicated with acute encephalopathy. She
      showed consciousness disturbance and convulsions followed by severe brain damage,
      a rare complication in RSV infection. Patients with severe neuromuscular diseases
      are vulnerable to RSV infection. Prophylactic interventions should be
      recommended.

PMID- 23005905
TI  - Neonatal iliopsoas abscess.
AB  - Iliopsoas abscess (IPA) is rare in children, particularly in neonates. A male
      neonate was born at 38 weeks of gestation with a weight of 2915 g. On day 22
      after birth, his family noticed that his right thigh was swollen. Abdominal
      computed tomography showed a mass extending to the right iliopsoas from the right
      thigh with thick septa. Puncture to the right groin yielded purulent fluid, and
      so a diagnosis of abscess was made. The puncture was followed by surgical
      drainage through a small inguinal incision, and the abscess cavity was irrigated
      thoroughly using normal saline. Culture of abscess fluid was positive for
      Streptococcus pneumoniae, so intravenous ABPC infusion was continued. The
      postoperative magnetic resonance imaging indicate that the IPA was derived from
      arthritis of the hip, and the patients received Riemenbugel for the incomplete
      hip dislocation. He is doing well at 2 years of age.

PMID- 23005906
TI  - Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral
      nutrition.
AB  - This report describes a small-for-date extremely low birth weight infant who
      manifested bradycardic events, respiratory failure, and hemolytic jaundice during
      her first week of life. These complications were attributed to severe
      hypophosphatemia and hypokalemia. Inadequate supply and refeeding syndrome
      triggered by early aggressive parenteral nutrition were responsible for
      electrolyte abnormalities.

PMID- 23005907
TI  - Diagnostic tools of metabolic and structural brain disturbances in neonatal non
      ketotic hyperglycinemia.
AB  - Non-ketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder of
      glycine metabolism. We report a newborn case of NKH and discuss the effects of
      this rare disease on brain metabolism and structure together with amplitude
      integrated electroencephalography, cranial magnetic resonance and magnetic
      resonance spectroscopy findings which are very rarely reported together so far.

PMID- 23005908
TI  - Castleman disease in a child with short stature.
AB  - We report a 14-year-old boy with Castleman disease in this article. He complained
      of short stature, and his body height was 133.8 cm (<3rd percentile; z score 
      4.5). There was marked delay in the appearance of secondary sexual
      characteristics. He was found to have a remittent fever and a lower mid-abdominal
      tumor. Blood test revealed microcytic hypochromic anemia, thrombocytosis,
      polyclonal hypergammaglobulinemia, hyperfibrinogenemia, and elevated erythrocyte
      sedimentation rate. The serum IL-6 and C-reactive protein levels were increased.
      The mass was found to be mixed hyaline vascular and plasma cell type of Castleman
      disease through a pathological examination. Lymph nodes affected by Castleman
      disease cause overproduction of IL-6. It decreases IGF-1, IGFBP-3 and serum
      testosterone levels. As a result of tumorectomy, his short stature and delay in
      the development of secondary sexual characteristics were improved.

PMID- 23005909
TI  - A case of meningoencephalitis associated with macrolide-resistant Mycoplasma
      pneumoniae infection.
AB  - Mycoplasma pneumoniae, a common pathogen causing community-acquired pneumonia, is
      also known to cause meningoencephalitis in pediatric patients. We report herein a
      pediatric patient with meningoencephalitis and macrolide-resistant M. pneumoniae
      infection. We emphasize that macrolide-resistant M. pneumoniae must be taken into
      consideration in patients with encephalitis, along with consideration for using
      minocycline even in pediatric patients.

PMID- 23005910
TI  - Current status of hypothermia treatment for neonatal hypoxic-ischemic
      encephalopathy in Taiwan.

PMID- 23005911
TI  - Metabolic acidosis due to continuous drainage of massive chylous pleural effusion
      in two neonates.

PMID- 23005912
TI  - The role of anthropometry in designing for sustainability.
AB  - An understanding of human factors and ergonomics facilitates the design of
      artefacts, tasks and environments that fulfil their users' physical and cognitive
      requirements. Research in these fields furthers the goal of efficiently
      accommodating the desired percentage of user populations through enhanced
      awareness and modelling of human variability. Design for sustainability (DfS)
      allows for these concepts to be leveraged in the broader context of designing to
      minimise negative impacts on the environment. This paper focuses on anthropometry
      and proposes three ways in which its consideration is relevant to DfS: reducing
      raw material consumption, increasing usage lifetimes and ethical human resource
      considerations. This is demonstrated through the application of anthropometry
      synthesis, virtual fitting, and sizing and adjustability allocation methods in
      the design of an industrial workstation seat for use in five distinct global
      populations. This work highlights the importance of and opportunities for using
      ergonomic design principles in DfS efforts. PRACTITIONER SUMMARY: This research
      demonstrates the relevance of some anthropometry-based ergonomics concepts to the
      field of design for sustainability. A global design case study leverages human
      variability considerations in furthering three sustainable design goals: reducing
      raw material consumption, increasing usage lifetimes and incorporating ethical
      human resource considerations in design.

PMID- 23005913
TI  - Photophysical properties of 7-(diethylamino)coumarin-3-carboxylic acid in the
      nanocage of cyclodextrins and in different solvents and solvent mixtures.
AB  - The photophysical properties of 7-(diethylamino) coumarin-3-carboxylic acid (7
      DCCA) were studied in cyclodextrins (alpha, beta, gamma,-CDs), different neat
      solvents and solvent mixtures by using steady state absorption, emission and time
      resolved fluorescence spectroscopy. We have observed that with gradual increase
      in concentration of beta-CD the fluorescence quantum yield and lifetime decreased
      in a regular pattern whereas with gradual increase in concentration of gamma-CD
      the fluorescence quantum yield and lifetime gradually increased. With addition of
      urea, the fluorescence quantum yield and lifetime of 7-DCCA in CDs increased.
      Binding constant calculation shows that 7-DDCA forms 1:1 complex with beta-CD and
      with gamma-CD it forms 1:1 and 1:2 (guest:host) inclusion complex. We proposed
      that the dye molecule formed capping complex with beta-CD by means of hydrogen
      bonding and after addition of urea the hydrogen bonding network broke down and
      part of dye molecule entered inside the cavity of beta-CD. The photophysics of 7
      DCCA was studied in dioxane-water mixture and ethylene glycol-acetonitrile
      mixture to know the effect of polarity and viscosity of the media. The
      photophysics of 7-DCCA was also studied in different neat solvents. It was found
      that the photophysics of 7-DCCA depended on the structural feature of the
      solvents and solvent mixtures.

PMID- 23005915
TI  - Complications and late outcome in transperitoneal laparoscopic heminephrectomy
      for duplex kidney in children.
AB  - PURPOSE: We report our experience with laparoscopic heminephrectomy (LH) in
      children with duplex kidneys, emphasizing complications and late outcomes, and
      including anatomic and functional aspects. PATIENTS AND METHODS: We
      retrospectively reviewed medical data of 28 children with a duplex kidney who
      underwent LH. Complications were evaluated according to the Savata and Clavien
      classiffication systems. RESULTS: Nineteen upper (67.8%) and 9 (32.1%) lower
      moieties were removed. All laparoscopic procedures were completed as planned
      without conversion. There were three (10.5%) cases of intraoperative bleeding
      successfully controlled by compression with gauze. Complications after surgery
      included two urinomas (7%), one intra-abdominal hematoma (3.5%), and two cases of
      complete functional loss (7%) because of torsion of the remnant upper pole. In
      six (21.4%) cases, a cyst at the resection margin of the kidney remnant was
      found. The function of the remnant pole was preserved in 23 (82.1%) cases and
      decreased in approximately 5% in 3 (10.5%). CONCLUSIONS: The anatomic and
      functional outcomes of LH must be evaluated with imaging studies and nuclear
      scintigraphy to rule out structural abnormalities and functional impairment. An
      extensive dissection in the lower pole LH can lead to the upper moiety torsion
      after surgery.

PMID- 23005914
TI  - Glycosaminoglycan-binding hydrogels enable mechanical control of human
      pluripotent stem cell self-renewal.
AB  - Reaping the promise of human embryonic stem (hES) cells hinges on effective
      defined culture conditions. Efforts to identify chemically defined environments
      for hES cell propagation would benefit from understanding the relevant functional
      properties of the substratum. Biological materials are often employed as
      substrata, but their complexity obscures a molecular level analysis of their
      relevant attributes. Because the properties of hydrogels can be tuned and altered
      systematically, these materials can reveal the impact of substratum features on
      cell fate decisions. By tailoring the peptide displayed to cells and the
      substrate mechanical properties, a hydrogel was generated that binds hES cell
      surface glycosaminoglycans (GAGs) and functions robustly in a defined culture
      medium to support long-term hES cell self-renewal. A key attribute of the
      successful GAG-binding hydrogels is their stiffness. Only stiff substrates
      maintain hES cell proliferation and pluripotency. These findings indicate that
      cells can respond to mechanical information transmitted via GAG engagement.
      Additionally, we found that the stiff matrices afforded activation of the
      paralogous proteins YAP/TAZ, which are transcriptional coactivators implicated in
      mechanosensing and hES cell pluripotency. These results indicate that the
      substratum mechanics can be tuned to activate specific pathways linked to
      pluripotency. Because several different hES and induced pluripotent stem cell
      lines respond similarly, we conclude that stiff substrata are more effective for
      the long-term propagation of human pluripotent stem cells.

PMID- 23005916
TI  - Preparation of brominated 2-alkoxythiophenes via oxidation and etherification of
      2-thienyltrifluoroborate salts.
AB  - The synthesis of ring brominated long-chain 2-alkoxythiophenes is reported,
      involving mild (Oxone) oxidation of readily prepared 2-thienyltrifluoroborate
      salts followed by Mitsunobu etherification. Both procedures are operationally
      straightforward and use inexpensive reagents. Using this approach, several novel
      mono- and dibrominated octyloxythiophenes with previously elusive substitution
      patterns were prepared. One such compound was elaborated to a novel 5
      alkoxythieno[3,2-b]thiophene-2-carboxylate ester, marking the first synthetic
      entry into this family of compounds.

PMID- 23005918
TI  - TAML activator-based amperometric analytical devices as alternatives to
      peroxidase biosensors.
AB  - The ferric TAML catalysts [Fe{C(6)H(2)-1,2-( NCOCMe(2)NCO)(2)CMe(2)}(OH(2))](-)
      (1) with counterions Na(+) (a) and PPh(4)(+) (b) function similar to horseradish
      peroxidase in the mediated electron transfer relays, which constitute a basis for
      amperometric biosensors. The mediators are mono- and bis-cyclometalated Ru and Os
      compounds of the type of [M(C~N)(x)(N~N)(3-x)](m+) with x = 1 and 2 (N~N = 2,2'
      bipyridine, (-)C~N = 2-phenylpyridinato). Cyclic voltammograms of the Ru and Os
      compounds are not affected by 1a though cathodic currents increase drastically in
      the presence of hydrogen peroxide. The reduction potentials of [M(C~N)(x)(N~N)(3
      x)](m+) complexes vary with both the nature of metal (Ru or Os) and the number of
      cyclometalated ligands x (1 or 2) and therefore the potential of working
      electrode can be set in the range of from -0.1 to +0.6 V versus the normal
      hydrogen electrode (NHE). A prototype of a biosensor for H(2)O(2) is described,
      in which the 1b catalyst and [Os(C~N)(2)(N~N)](+) mediator were coimmobilized on
      the surface of the glassy carbon electrode using a polymeric coating.

PMID- 23005917
TI  - Are language production problems apparent in adults who no longer meet diagnostic
      criteria for attention-deficit/hyperactivity disorder?
AB  - In this study, we examined sentence production in a sample of adults (N = 21) who
      had had attention-deficit/hyperactivity disorder (ADHD) as children, but as
      adults no longer met DSM-IV diagnostic criteria (APA, 2000). This "remitted"
      group was assessed on a sentence production task. On each trial, participants saw
      two objects and a verb. Their task was to construct a sentence using the objects
      as arguments of the verb. Results showed more ungrammatical and disfluent
      utterances with one particular type of verb (i.e., participle). In a second set
      of analyses, we compared the remitted group to both control participants and a
      "persistent" group, who had ADHD as children and as adults. Results showed that
      remitters were more likely to produce ungrammatical utterances and to make repair
      disfluencies compared to controls, and they patterned more similarly to ADHD
      participants. Conclusions focus on language output in remitted ADHD, and the role
      of executive functions in language production.

PMID- 23005919
TI  - Comparison of the bronchodilating effects of albuterol delivered by valved vs.
      non-valved spacers in pediatric asthma.
AB  - INTRODUCTION: Inhaled therapy using a metered-dose inhaler (MDI) with attached
      valved holding chamber has been increasingly recognized as the optimal method for
      delivering bronchodilators for asthma treatment. However, mainly due to the high
      cost of these valved holding chambers in many developing countries, the use of
      non-valved spacers is frequent, despite the scarce evidence that supports their
      efficacy. The aim of this study was to compare the bronchodilator response to
      albuterol administered by MDI with and without a valved spacer. METHODS: In a
      randomized, two-period, two-sequence crossover clinical trial, we analyzed 31
      stable asthmatic children (6-18 yrs of age) on two consecutive days, who were
      randomly assigned to receive 100 MUg of albuterol MDI through either a locally
      produced valved spacer or a non-valved spacer. The next day, a crossover
      treatment was employed through the use of the other spacer. Spirometry was
      recorded before and after each albuterol administration. RESULTS: As we were not
      able to identify any sequence or carryover effect, we tested for treatment
      effects in both periods. No significant differences in the absolute change in
      FEV(1) (0.20 +/- 0.17 vs. 0.18 +/- 0.16, p = 0.63), FVC (0.07 +/- 0.13 vs. 0.07
      +/- 0.16, p = 0.88), or MMEF (0.49 +/- 0.31 vs. 0.43 +/- 0.39, p = 0.53) after
      bronchodilator administration were found between the use of valved and non-valved
      spacers. CONCLUSIONS: In stable asthmatic children, albuterol administered
      through MDI using a non-valved spacer produces a bronchodilator response similar
      to that of a spacer with a valve that requires an inhalatory opening pressure
      (with flows between 2 and 32 l/min) that even toddlers with bronchial obstruction
      can easily generate.

PMID- 23005920
TI  - Effects of brain contusion on mild traumatic brain-injured patients.
AB  - Traumatic brain injury (TBI) is an important health issue with high prevalence.
      The most common type of TBI is mild TBI (MTBI). MTBI is known as a condition with
      self-limited symptoms; however, it could cause some structural abnormalities of
      brain and become complicated. Visible structural brain damage could have an
      important effect on recovery after MTBI, but the outcome is not fully understood.
      This study investigated the clinical course of MTBI patients with the existence
      of contusion in computed tomography (CT) imaging. Fifty patients with MTBI and
      simultaneous brain contusion in CT scan were enrolled according to specific
      exclusion criteria in 14 month. Patients were followed up for two weeks after
      their first arrival for neurosurgical interventions, decreased level of
      consciousness, and other neurological complications. Presence of neurological
      symptoms increased duration of hospital stay and number of CT scans. Forty-two
      percent of MTBI patients with contusion did not have any objective neurological
      signs. Fifty percent returned to the hospital with neurologic symptoms and signs.
      Leading causes were headache followed by seizure and dizziness. Rehospitalization
      was increased in the patients with altered level of consciousness. The size of
      brain contusion increased in two patients without further need for neurosurgical
      intervention. Contusion alone did not worsen the prognosis of patients in short
      term follow-up and did not cause neurosurgical interventions.

PMID- 23005922
TI  - Large psoas haematoma and femoral neuropathy in a patient with type 2B von
      Willebrand's disease.

PMID- 23005921
TI  - Expression of p16 alone does not differentiate between Spitz nevi and Spitzoid
      melanoma.
AB  - BACKGROUND: Spitz nevi and Spitzoid melanomas show overlapping histopathologic
      features, often making the diagnosis challenging. The p16 protein functions as a
      tumor suppressor and loss of its expression may be seen in some melanomas.
      METHODS: We evaluated 18 Spitz nevi and 19 Spitzoid melanomas from the Yale
      Spitzoid Neoplasm Repository for p16 expression. A staining intensity score (SIS)
      was calculated by multiplying a score for the percentage of stained cells (0-3)
      by a score for staining intensity (0-3). RESULTS: Staining with p16 was positive
      in 15/18 (83%) Spitz nevi and 15/19 (79%) Spitzoid melanomas (p = 0.73). Both
      Spitz nevi and Spitzoid melanomas had a similar SISs, 4.9 and 3.8, respectively
      (p = 0.057). All 19 patients with Spitzoid melanomas had poor outcome with either
      death (6 patients) or metastases (13 patients) at a median (3 years) and mean
      (5.4 years) follow up. In contrast, all 18 patients with Spitz nevi had a benign
      course with no adverse events at a median (4 years) and mean (4 years) follow up.
      CONCLUSIONS: We found no significant difference in p16 staining in Spitz nevi and
      Spitzoid melanomas. We conclude that p16 does not appear to be a useful
      immunohistochemical marker in distinguishing between Spitz nevi and Spitzoid
      melanomas.

PMID- 23005923
TI  - The response of cementoblasts to calcium phosphate resin-based and calcium
      silicate-based commercial sealers.
AB  - AIM: To investigate cell viability and gene expression of cementoblasts (OCCM.30)
      exposed to extractable components released by resin-based sealers with different
      chemical composition Hybrid Root Seal (HRS), SimpliSeal (SS), Real Seal (RS) and
      AH Plus (AH) and by a MTA-based sealers Tech Biosealer Endo (TBE). METHODOLOGY:
      Discs of all materials were prepared and allowed to set in humid conditions at 37
      degrees  for 48 h. The discs were then incubated for 72 h at 37  degrees C to
      obtain material extracts (1/1) in DMEM. The extracts containing the components
      released by the sealers were filtered and other dilutions (1/2, 1/4) were
      prepared from the original solution (1/1). Original and diluted solutions were
      tested on the cementoblasts. Impedance-based real-time cell analysis (RTCA) was
      used to evaluate cell viability, quantitative real-time polymerase chain reaction
      (QRT-PCR) was used to examine the expression of mineralization-related genes
      (osteocalcin; OCN, Runt-related transcription factor-2; Runx2, collagen type 1;
      COL I, alkaline phosphatase; ALP). For statistical analysis, one-way analysis of
      variance (anova) and Tukey's honestly significant difference (HSD) tests were
      used. RESULTS: TBE (1/2), RS (1/2, 1/4), and HRS (1/2, 1/4) significantly
      decreased cell viability (P < 0.001). AH (1/2, 1/4) and SS (1/2, 1/4) had similar
      cell viability to the control at 30 h. All tested materials significantly
      decreased cell viability when compared to the control group except AH (1/2, 1/4)
      and SS (1/4) at 90 h. All of the tested sealers reduced COL I mRNA expressions
      when compared to the control. SS was associated with significant increases in OCN
      and Runx2 mRNA expressions when compared to the control (P < 0.001). Whereas all
      of the dilutions of TBE, RS and HRS significantly decreased BSP mRNA expressions
      (P < 0,001), 1/2 and 1/4 dilutions of SS increased BSP mRNA expression (P <
      0,001). Except the 1/4 dilutions of AH and SS, all the sealer dilutions
      significantly reduced ALP mRNA expression in cementoblasts (P < 0,001).
      CONCLUSIONS: SimpliSeal and AH Plus resulted in more favourable response to
      cementoblasts because of their regulation potential on the mineralized tissue
      associated protein's mRNA expressions.

PMID- 23005924
TI  - Measurement of S-phase duration of adult stem cells in the flatworm Macrostomum
      lignano by double replication labelling and quantitative colocalization analysis.
AB  - Platyhelminthes are highly attractive models for addressing fundamental aspects
      of stem cell biology in vivo. These organisms possess a unique stem cell system
      comprised of neoblasts that are the only proliferating cells during adulthood. We
      have investigated Ts (S-phase duration) of neoblasts during homoeostasis and
      regeneration in the flatworm, Macrostomum lignano. A double immunohistochemical
      technique was used, performing sequential pulses with the thymidine analogues
      CldU (chlorodeoxyuridine) and IdU (iododeoxyuridine), separated by variable chase
      times in the presence of colchicine. Owing to the localized nature of the
      fluorescent signals (cell nuclei) and variable levels of autofluorescence,
      standard intensity-based colocalization analyses could not be applied to
      accurately determine the colocalization. Therefore, an object-based
      colocalization approach was devised to score the relative number of double
      positive cells. Using this approach, Ts (S-phase duration) in the main population
      of neoblasts was ~13 h. During early regeneration, no significant change in Ts
      was observed.

PMID- 23005925
TI  - Orthogonality catastrophe in quantum sticking.
AB  - We show that the orthogonality catastrophe can dramatically affect the
      probability with which an ultralow energy atom or ion will stick to a surface. We
      predict new energy-dependent scaling laws for the sticking probability in this
      low-energy regime. We provide numerical results of this theory for the case of
      ultracold electrons sticking to the surface of highly porous silicon and show
      that the sticking probability can differ substantially from that calculated with
      perturbation theory. We then generalize our results for finite surface
      temperatures and find surprisingly that the sticking probability can change
      sharply, vanishing below a critical incident energy that varies with the surface
      temperature. We describe in detail this superreflective surface phase for
      ultralow energy matter waves where the reflection coefficient is strictly equal
      to one.

PMID- 23005926
TI  - All entangled pure states violate a single Bell's inequality.
AB  - We show that a single Bell's inequality with two dichotomic observables for each
      observer, which originates from Hardy's nonlocality proof without inequalities,
      is violated by all entangled pure states of a given number of particles, each of
      which may have a different number of energy levels. Thus Gisin's theorem is
      proved in its most general form from which it follows that for pure states Bell's
      nonlocality and quantum entanglement are equivalent.

PMID- 23005927
TI  - Reliable quantum state tomography.
AB  - Quantum state tomography is the task of inferring the state of a quantum system
      by appropriate measurements. Since the frequency distributions of the outcomes of
      any finite number of measurements will generally deviate from their asymptotic
      limits, the estimates computed by standard methods do not in general coincide
      with the true state and, therefore, have no operational significance unless their
      accuracy is defined in terms of error bounds. Here we show that quantum state
      tomography, together with an appropriate data analysis procedure, yields reliable
      and tight error bounds, specified in terms of confidence regions-a concept
      originating from classical statistics. Confidence regions are subsets of the
      state space in which the true state lies with high probability, independently of
      any prior assumption on the distribution of the possible states. Our method for
      computing confidence regions can be applied to arbitrary measurements including
      fully coherent ones; it is practical and particularly well suited for tomography
      on systems consisting of a small number of qubits, which are currently in the
      focus of interest in experimental quantum information science.

PMID- 23005928
TI  - He-McKellar-Wilkens topological phase in atom interferometry.
AB  - We report an experimental test of the topological phase predicted by He and
      McKellar in 1993 and by Wilkens in 1994: this phase, which appears when an
      electric dipole propagates in a magnetic field, is connected to the Aharonov
      Casher effect by electric-magnetic duality. The He-McKellar-Wilkens phase is
      quite small, at most 27 mrad in our experiment, and this experiment requires the
      high phase sensitivity of our atom interferometer with spatially separated arms
      as well as symmetry reversals such as the direction of the electric and magnetic
      fields. The measured value of the He-McKellar-Wilkens phase differs by 31% from
      its theoretical value, a difference possibly due to some as yet uncontrolled
      systematic errors.

PMID- 23005929
TI  - Chemical-potential route: a hidden Percus-Yevick equation of state for hard
      spheres.
AB  - The chemical potential of a hard-sphere fluid can be expressed in terms of the
      contact value of the radial distribution function of a solute particle with a
      diameter varying from zero to that of the solvent particles. Exploiting the
      explicit knowledge of such a contact value within the Percus-Yevick theory, and
      using standard thermodynamic relations, a hitherto unknown Percus-Yevick equation
      of state, p/rhok(B)T = -(9/eta) ln(1-eta)-(16-31eta)/2(1-eta)(2), is unveiled.
      This equation of state turns out to be better than the one obtained from the
      conventional virial route. Interpolations between the chemical-potential and
      compressibility routes are shown to be more accurate than the widely used
      Carnahan-Starling equation of state. The extension to polydisperse hard-sphere
      systems is also presented.

PMID- 23005930
TI  - Nonequilibrium phase transitions and a nonequilibrium critical point from anti-de
      Sitter space and conformal field theory correspondence.
AB  - We find novel phase transitions and critical phenomena that occur only outside
      the linear-response regime of current-driven nonequilibrium states. We consider
      the strongly interacting (3+1)-dimensional N = 4 large-N(c) SU(N(c))
      supersymmetric Yang-Mills theory with a single flavor of fundamental N = 2
      hypermultiplet as a microscopic theory. We compute its nonlinear nonballistic
      quark-charge conductivity by using the AdS/CFT correspondence. We find that the
      system exhibits a novel nonequilibrium first-order phase transition where the
      conductivity jumps and the sign of the differential conductivity flips at finite
      current density. A nonequilibrium critical point is discovered at the end point
      of the first-order regime. We propose a nonequilibrium steady-state analogue of
      thermodynamic potential in terms of the gravity-dual theory in order to define
      the transition point. Nonequilibrium analogues of critical exponents are proposed
      as well. The critical behavior of the conductivity is numerically confirmed on
      the basis of these proposals. The present work provides a new example of
      nonequilibrium phase transitions and nonequilibrium critical points.

PMID- 23005931
TI  - General dynamical density functional theory for classical fluids.
AB  - We study the dynamics of a colloidal fluid including inertia and hydrodynamic
      interactions, two effects which strongly influence the nonequilibrium properties
      of the system. We derive a general dynamical density functional theory which
      shows very good agreement with full Langevin dynamics. In suitable limits, we
      recover existing dynamical density functional theories and a Navier-Stokes-like
      equation with additional nonlocal terms.

PMID- 23005932
TI  - Thermodynamics of prediction.
AB  - A system responding to a stochastic driving signal can be interpreted as
      computing, by means of its dynamics, an implicit model of the environmental
      variables. The system's state retains information about past environmental
      fluctuations, and a fraction of this information is predictive of future ones.
      The remaining nonpredictive information reflects model complexity that does not
      improve predictive power, and thus represents the ineffectiveness of the model.
      We expose the fundamental equivalence between this model inefficiency and
      thermodynamic inefficiency, measured by dissipation. Our results hold arbitrarily
      far from thermodynamic equilibrium and are applicable to a wide range of systems,
      including biomolecular machines. They highlight a profound connection between the
      effective use of information and efficient thermodynamic operation: any system
      constructed to keep memory about its environment and to operate with maximal
      energetic efficiency has to be predictive.

PMID- 23005933
TI  - Collisional Penrose process near the horizon of extreme Kerr black holes.
AB  - Collisions of particles in black hole ergospheres may result in an arbitrarily
      large center-of-mass energy. This led recently to the suggestion [M. Banados, J.
      Silk, and S. M. West, Phys. Rev. Lett. 103, 111102 (2009)] that black holes can
      act as ultimate particle accelerators. If the energy of an outgoing particle is
      larger than the total energy of the infalling particles, the energy excess must
      come from the rotational energy of the black hole and hence, a Penrose process is
      involved. However, while the center-of-mass energy diverges, the position of the
      collision makes it impossible for energetic particles to escape to infinity.
      Following an earlier work on collisional Penrose processes [T. Piran and J.
      Shaham, Phys. Rev. D 16, 1615 (1977)], we show that even under the most favorable
      idealized conditions the maximal energy of an escaping particle is only a modest
      factor above the total initial energy of the colliding particles. This implies
      that one should not expect collisions around a black hole to act as spectacular
      cosmic accelerators.

PMID- 23005934
TI  - Primordial non-Gaussianity in the forest: 3D bispectrum of Lyman-alpha flux
      spectra along multiple lines of sight.
AB  - We investigate the possibility of constraining primordial non-Gaussianity using
      the 3D bispectrum of the Lyman (Ly)-alpha forest. The strength of the quadratic
      non-Gaussian correction to an otherwise Gaussian primordial gravitational field
      is assumed to be dictated by a single parameter f(NL). We present the first
      prediction for bounds on f(NL) using Ly-alpha flux spectra along multiple lines
      of sight. The 3D Ly-alpha transmitted flux field is modeled as a biased tracer of
      the underlying matter distribution sampled along 1D skewers corresponding to
      quasar sight lines. The precision to which f(NL) can be constrained depends on
      the survey volume, pixel noise, and aliasing noise (arising from discrete
      sampling of the density field). We consider various combinations of these factors
      to predict bounds on f(NL). We find that in an idealized situation of full sky
      survey and negligible Poisson noise one may constrain f(NL)~23 in the equilateral
      limit. Assuming a Ly-alpha survey covering large parts of the sky (k(min) = 8 *
      10(-4) Mpc(-1)) and with a quasar density of n = 5 * 10(-3) Mpc(-2), it is
      possible to constrain f(NL)~100 for equilateral configurations. The possibility
      of measuring f(NL) at a precision comparable to large scale structure studies
      maybe useful for joint constraining of inflationary scenarios using different
      data sets.

PMID- 23005936
TI  - Semiclassical realization of infrared renormalons.
AB  - Perturbation series in quantum field theory (QFT) are generally divergent
      asymptotic series which are also typically not Borel resummable in the sense that
      the resummed series is ambiguous. The ambiguity is associated with singularities
      in the Borel plane on the positive real axis. In quantum mechanics there are
      cases in which the ambiguity that arises in perturbation theory cancels against a
      similarly ambiguous contribution from instanton-anti-instanton events. In
      asymptotically free gauge theories, this mechanism does not suffice because
      perturbation theory develops ambiguities associated with singularities in the
      Borel plane which are closer to the origin by a factor of about N (the rank of
      the gauge group) compared to the singularities realized by instanton events.
      These are called IR renormalon poles, and on R^{4} they do not possess any known
      semiclassical realization. By using continuity on R(3) * S(1), and by
      generalizing the works of Bogomolny and Zinn-Justin to QFT, we identify saddle
      point field configurations, e.g., bion-antibion events, corresponding to
      singularities in the Borel plane which are of order N times closer to the origin
      than the four-dimensional instanton-anti-instanton singularities in the Borel
      plane. We conjecture that these are the leading singularities in the Borel plane
      and that they are the incarnation of the elusive renormalons in the weak coupling
      regime.

PMID- 23005935
TI  - First constraints on the running of non-Gaussianity.
AB  - We use data from the Wilkinson Microwave Anisotropy probe temperature maps to
      constrain a scale-dependent generalization of the popular "local" model for
      primordial non-Gaussianity. In the model where the parameter f(NL) is allowed to
      run with scale k, f(NL)(k) = f*(NL) (k/k(piv))(n)(fNL), we constrain the running
      to be n(f)(NL) = 0.30(-1.2)(+1.9) at 95% confidence, marginalized over the
      amplitude f*(NL). The constraints depend somewhat on the prior probabilities
      assigned to the two parameters. In the near future, constraints from a
      combination of Planck and large-scale structure surveys are expected to improve
      this limit by about an order of magnitude and usefully constrain classes of
      inflationary models.

PMID- 23005941
TI  - J/psi suppression in p-A collisions from parton energy loss in cold QCD matter.
AB  - The effects of energy loss in cold nuclear matter on J/psi suppression in p-A
      collisions are studied. A simple model based on first principles and depending on
      a single free parameter is able to reproduce J/psi suppression data at large x(F)
      and at various center-of-mass energies. These results strongly support energy
      loss as a dominant effect in quarkonium suppression. They also give some hint on
      its hadroproduction mechanism suggesting color neutralization to happen on long
      time scales. Predictions for J/psi and Upsilon suppression in p-Pb collisions at
      the LHC are made.

PMID- 23005943
TI  - Molecular-frame 3D photoelectron momentum distributions by tomographic
      reconstruction.
AB  - Naphthalene molecules are fixed in space by a laser field and rotated, in 2
      degrees  steps, over 180 degrees . For each orientation, they are ionized by an
      intense, circularly polarized femtosecond laser pulse, and the 2D projection of
      the photoelectron momentum distribution is recorded. The molecular-frame 3D
      momentum distribution is obtained by tomographic reconstruction from all 90
      projections. It reveals an anisotropic electron distribution, angularly shifted
      in the polarization plane, that is not accessible by the 2D momentum images. Our
      theoretical analysis shows that the magnitude of the angular shift is very
      sensitive to the exact form of the laser-modified molecular potential.

PMID- 23005944
TI  - Single ion as a three-body reaction center in an ultracold atomic gas.
AB  - We report on three-body recombination of a single trapped Rb(+) ion and two
      neutral Rb atoms in an ultracold atom cloud. We observe that the corresponding
      rate coefficient K(3) depends on collision energy and is about a factor of 1000
      larger than for three colliding neutral Rb atoms. In the three-body recombination
      process large energies up to several 0.1 eV are released leading to an ejection
      of the ion from the atom cloud. It is sympathetically recooled back into the
      cloud via elastic binary collisions with cold atoms. Further, we find that the
      final ionic product of the three-body processes is again an atomic Rb(+) ion
      suggesting that the ion merely acts as a catalyzer, possibly in the formation of
      deeply bound Rb(2) molecules.

PMID- 23005945
TI  - Strong molecular alignment dependence of H2 electron impact ionization dynamics.
AB  - Low-energy (E(0) = 54 eV) electron impact single ionization of molecular hydrogen
      (H(2)) has been investigated as a function of molecular alignment in order to
      benchmark recent theoretical predictions [Colgan et al., Phys. Rev. Lett. 101,
      233201 (2008) and Al-Hagan et al., Nature Phys. 5, 59 (2009)]. In contrast to any
      previous work, we observe distinct alignment dependence of the (e,2e) cross
      sections in the perpendicular plane in good overall agreement with results from
      time-dependent close-coupling calculations. The cross section behavior can be
      consistently explained by a rescattering of the ejected electron in the molecular
      potential resulting in an effective focusing along the molecular axis.

PMID- 23005946
TI  - Fundamental limits of classical and quantum imaging.
AB  - Quantum imaging promises increased imaging performance over classical protocols.
      However, there are a number of aspects of quantum imaging that are not well
      understood. In particular, it has been unknown so far how to compare classical
      and quantum imaging procedures. Here, we consider classical and quantum imaging
      in a single theoretical framework and present general fundamental limits on the
      resolution and the deposition rate for classical and quantum imaging. The
      resolution can be estimated from the image itself. We present a utility function
      that allows us to compare imaging protocols in a wide range of applications.

PMID- 23005947
TI  - Weak qubit measurement with a nonlinear cavity: beyond perturbation theory.
AB  - We analyze the use of a driven nonlinear cavity to make a weak continuous
      measurement of a dispersively coupled qubit. We calculate the backaction
      dephasing rate and measurement rate beyond leading-order perturbation theory
      using a phase-space approach which accounts for cavity noise squeezing.
      Surprisingly, we find that increasing the coupling strength beyond the regime
      describable by leading-order perturbation theory (i.e., linear response) allows
      one to come significantly closer to the quantum limit on the measurement
      efficiency. We interpret this behavior in terms of the non-Gaussian photon number
      fluctuations of the nonlinear cavity. Our results are relevant to recent
      experiments using superconducting microwave circuits to study quantum
      measurement.

PMID- 23005948
TI  - Commensurate two-quantum coherences induced by time-delayed THz fields.
AB  - The interaction of carbonyl sulfide dipolar gas molecules with two time-delayed,
      single-cycle THz pulses is shown both experimentally and theoretically to induce
      two-quantum rotational coherences that are significantly enhanced with respect to
      those induced by one THz pulse, depending on the relative delay of the pulses.
      The underlying phenomenon is quite general in that it can occur even after a
      single THz pulse if more than one molecular species is present, since the free
      induction decay emitted by one species (demonstrated here by atmospheric water
      vapor) can provide the second field interaction for the other.

PMID- 23005938
TI  - Combined search for the standard model Higgs boson decaying to bb using the D0
      run II data set.
AB  - We present the results of the combination of searches for the standard model
      Higgs boson produced in association with a W or Z boson and decaying into bb
      using the data sample collected with the D0 detector in pp collisions at ?s =
      1.96 TeV at the Fermilab Tevatron Collider. We derive 95% C.L. upper limits on
      the Higgs boson cross section relative to the standard model prediction in the
      mass range 100 GeV <= M(H) <= 150 GeV, and we exclude Higgs bosons with masses
      smaller than 102 GeV at the 95% C.L. In the mass range 120 GeV <= M(H) <=145 GeV,
      the data exhibit an excess above the background prediction with a global
      significance of 1.5 standard deviations, consistent with the expectation in the
      presence of a standard model Higgs boson.

PMID- 23005939
TI  - Search for the standard model Higgs boson in ZH->l(+)l(-)bb production with the
      D0 detector in 9.7 fb(-1) of pp collisions at ?s = 1.96 TeV.
AB  - We present a search for the standard model (SM) Higgs boson produced in
      association with a Z boson in 9.7 fb(-1) of pp collisions collected with the D0
      detector at the Fermilab Tevatron Collider at ?s = 1.96 TeV. Selected events
      contain one reconstructed Z->e(+)e(-) or Z->MU(+)MU(-) candidate and at least two
      jets, including at least one jet identified as likely to contain a b quark. To
      validate the search procedure, we also measure the cross section for ZZ
      production in the same final state. It is found to be consistent with its SM
      prediction. We set upper limits on the ZH production cross section times
      branching ratio for H->bb at the 95% C.L. for Higgs boson masses 90 <= M(H) <=
      150 GeV. The observed (expected) limit for M(H) = 125 GeV is 7.1 (5.1) times the
      SM cross section.

PMID- 23005949
TI  - Rotational quantum friction.
AB  - We investigate the frictional forces due to quantum fluctuations acting on a
      small sphere rotating near a surface. At zero temperature, we find the frictional
      force near a surface to be several orders of magnitude larger than that for the
      sphere rotating in vacuum. For metallic materials with typical conductivity,
      quantum friction is maximized by matching the frequency of rotation with the
      conductivity. Materials with poor conductivity are favored to obtain large
      quantum frictions. For semiconductor materials that are able to support surface
      plasmon polaritons, quantum friction can be further enhanced by several orders of
      magnitude due to the excitation of surface plasmon polaritons.

PMID- 23005950
TI  - Small ion-temperature-gradient scale length and reduced heat diffusivity at large
      hydrogen isotope mass in conventional H-mode plasmas.
AB  - The dependence of the ion-temperature-gradient scale length on the hydrogen
      isotope mass was examined in conventional H-mode plasmas in JT-60U tokamak. While
      identical profiles for density and temperature were obtained for hydrogen and
      deuterium plasmas, the ion conductive heat flux necessary for hydrogen to sustain
      the same ion temperature profile was two times that required for deuterium,
      resulting in a clearly higher ion heat diffusivity for hydrogen at the same ion
      temperature-gradient scale length. On the other hand, the ion-temperature
      gradient scale length for deuterium is less than that for hydrogen at a given ion
      heat diffusivity.

PMID- 23005951
TI  - Harmonic generation from relativistic plasma surfaces in ultrasteep plasma
      density gradients.
AB  - Harmonic generation in the limit of ultrasteep density gradients is studied
      experimentally. Observations reveal that, while the efficient generation of high
      order harmonics from relativistic surfaces requires steep plasma density scale
      lengths (L(p)/lambda < 1), the absolute efficiency of the harmonics declines for
      the steepest plasma density scale length L(p)->0, thus demonstrating that near
      steplike density gradients can be achieved for interactions using high-contrast
      high-intensity laser pulses. Absolute photon yields are obtained using a
      calibrated detection system. The efficiency of harmonics reflected from the laser
      driven plasma surface via the relativistic oscillating mirror was estimated to be
      in the range of 10(-4)-10(-6) of the laser pulse energy for photon energies
      ranging from 20-40 eV, with the best results being obtained for an intermediate
      density scale length.

PMID- 23005952
TI  - Three-dimensional mode conversion associated with kinetic Alfven waves.
AB  - We report the first three-dimensional (3D) ion particle simulation of mode
      conversion from a fast mode compressional wave to kinetic Alfven waves (KAWs)
      that occurs when a compressional mode propagates across a plasma boundary into a
      region of increasing Alfven velocity. The magnetic field is oriented in the z
      direction perpendicular to the gradients in the background density and magnetic
      field (x direction). Following a stage dominated by linear physics in which KAWs
      with large wave numbers k(x)rho(i)~1 (with rho(i) being the ion Larmor radius)
      are generated near the Alfven resonance surface, the growth of KAW modes with
      k(y)rho(i)~1 is observed in the nonlinear stage when the amplitude of KAWs
      generated by linear mode conversion becomes large enough to drive a nonlinear
      parametric decay process. The simulation provides a comprehensive picture of mode
      conversion and shows the fundamental importance of the 3D nonlinear physics in
      transferring energy to large perpendicular k(y) modes, which can provide large
      transport across plasma boundaries in space and laboratory plasmas.

PMID- 23005940
TI  - Search for the standard model Higgs boson in associated WH production in 9.7 fb(
      1) of pp collisions with the D0 detector.
AB  - We present a search for the standard model Higgs boson in final states with a
      charged lepton (electron or muon), missing transverse energy, and two or three
      jets, at least one of which is identified as a b-quark jet. The search is
      primarily sensitive to WH->lnubb production and uses data corresponding to 9.7
      fb(-1) of integrated luminosity collected with the D0 detector at the Fermilab
      Tevatron pp Collider at ?s = 1.96 TeV. We observe agreement between the data and
      the expected background. For a Higgs boson mass of 125 GeV, we set a 95% C.L.
      upper limit on the production of a standard model Higgs boson of 5.2 * sigma(SM),
      where sigma(SM) is the standard model Higgs boson production cross section, while
      the expected limit is 4.7 * sigma(SM).

PMID- 23005953
TI  - Strong compression of a magnetic field with a laser-accelerated foil.
AB  - We demonstrate the generation of high magnetic fields for condensed matter
      research using a high-power laser system. A cavity in which a seed magnetic field
      is applied is compressed by a kJ ns laser pulse. The time history of the
      compressed magnetic field is monitored by observing the Faraday effect rotation
      of polarization of a probe pulse in a glass fiber. To maintain a low-temperature
      condition in the final high-field region, we put a high-resistance foil around
      the final compression area. If we assume the length of the compression region is
      equal to the laser spot size, a magnetic field of more than 800 T is observed by
      Faraday rotation. Because of the large mass of the compression foil, this high
      magnetic field is sustained during almost 2 ns. During compression, a rarefaction
      wave from the backside of the accelerated foil and expanding material from the
      inner protection foil affect the magnetic field compression history, but the
      final compressed magnetic field strength agrees with the ratio between the
      initial sample area and the compressed cavity area.

PMID- 23005955
TI  - Simulating compact quantum electrodynamics with ultracold atoms: probing
      confinement and nonperturbative effects.
AB  - Recently, there has been much interest in simulating quantum field theory effects
      of matter and gauge fields. In a recent work, a method for simulating compact
      quantum electrodynamics (CQED) using Bose-Einstein condensates has been
      suggested. We suggest an alternative approach, which relies on single atoms in an
      optical lattice, carrying 2l + 1 internal levels, which converges rapidly to CQED
      as l increases. That enables the simulation of CQED in 2 + 1 dimensions in both
      the weak and the strong coupling regimes, hence, allowing us to probe confinement
      as well as other nonperturbative effects of the theory. We provide an explicit
      construction for the case l = 1 which is sufficient for simulating the effect of
      confinement between two external static charges.

PMID- 23005954
TI  - Probing phase fluctuations in a 2D degenerate Bose gas by free expansion.
AB  - We measure the power spectrum of the density distribution of a freely expanding
      two-dimensional (2D) degenerate Bose gas, where irregular density modulations
      gradually develop due to initial phase fluctuations in the sample. The spectrum
      has an oscillatory shape, where the peak positions are found to be independent of
      temperature and show scaling behavior in the course of expansion. The relative
      intensity of phase fluctuations is estimated from the normalized spectral peak
      strength and observed to decrease at lower temperatures, confirming the thermal
      nature of the phase fluctuations. We investigate the relaxation dynamics of
      nonequilibrium states using the power spectrum. Free vortices are observed with
      ring-shaped density ripples in a perturbed sample after a long relaxation time.

PMID- 23005942
TI  - Observation of direct-photon collective flow in Au + Au collisions at ?s(NN)] =
      200 GeV.
AB  - The second Fourier component v(2) of the azimuthal anisotropy with respect to the
      reaction plane is measured for direct photons at midrapidity and transverse
      momentum (p(T)) of 1-12 GeV/c in Au + Au collisions at ?s(NN)] = 200 GeV.
      Previous measurements of this quantity for hadrons with p(T) < 6 GeV/c indicate
      that the medium behaves like a nearly perfect fluid, while for p(T) > 6 GeV/c a
      reduced anisotropy is interpreted in terms of a path-length dependence for parton
      energy loss. In this measurement with the PHENIX detector at the Relativistic
      Heavy Ion Collider we find that for p(T) > 4 GeV/c the anisotropy for direct
      photons is consistent with zero, which is as expected if the dominant source of
      direct photons is initial hard scattering. However, in the p(T) < 4 GeV/c region
      dominated by thermal photons, we find a substantial direct-photon v(2) comparable
      to that of hadrons, whereas model calculations for thermal photons in this
      kinematic region underpredict the observed v(2).

PMID- 23005956
TI  - Electronic structure inheritance and pressure-induced polyamorphism in lanthanide
      based metallic glasses.
AB  - We report that a series of lanthanide-based bulk metallic glasses show a pressure
      induced polyamorphic phase transition observed by in situ angle-dispersive x-ray
      diffraction under high pressures. The transition started from a low-density state
      at lower pressures, and went through continuous densification ending with a high
      density state at higher pressures. We demonstrate that, under high pressure, this
      new type of polyamorphism in densely packed metallic glasses is inherited from
      its lanthanide-solvent constituent and related to the electronic structure of 4f
      electrons. The found electronic structure inheritance could provide the guidance
      for designing new metallic glasses with unique functional physical properties.

PMID- 23005957
TI  - Marginal stability constrains force and pair distributions at random close
      packing.
AB  - The requirement that packings of frictionless hard spheres, arguably the simplest
      structural glass, cannot be compressed by rearranging their network of contacts
      is shown to yield a new constraint on their microscopic structure. This
      constraint takes the form a bound between the distribution of contact forces P(f)
      and the pair distribution function g(r): if P(f)~f(theta) and g(r)~(r-sigma(0))(
      gamma), where sigma(0) is the particle diameter, one finds that gamma >= 1/(2 +
      theta). This bound plays a role similar to those found in some glassy materials
      with long-range interactions, such as the Coulomb gap in Anderson insulators or
      the distribution of local fields in mean-field spin glasses. There are grounds to
      believe that this bound is saturated, yielding a mechanism to explain the
      avalanches of rearrangements with power-law statistics that govern plastic flow
      in packings.

PMID- 23005958
TI  - Lattice anharmonicity in defect-free Pd nanowhiskers.
AB  - We have investigated anharmonic behavior of Pd by applying systematic nanoscale
      tensile testing to near defect-free nanowhiskers offering a large range of
      elastic strain. We measured size-dependent deviations from bulk elastic behavior
      in nanowhiskers with diameters as small as ~30 nm. In addition to size-dependent
      variations in Young's modulus in the small strain limit, we measured nonlinear
      elasticity at strains above ~1%. Both phenomena are attributed to higher-order
      elasticity in the bulklike core upon being biased from its equilibrium
      configuration due to the role of surface stresses in small volumes.
      Quantification of the size-dependent second- and third-order elastic moduli
      allows for calculation of intrinsic material nonlinearity parameters, e.g.,
      delta. Comparison of the size-independent values of delta in our nanowhiskers
      with studies on bulk fcc metals lends further insight into the role of length
      scales on both elastic and plastic mechanical behavior.

PMID- 23005959
TI  - Reactive gas environment induced structural modification of noble-transition
      metal alloy nanoparticles.
AB  - Noble-transition metal (noble=Pt,Au; transition=Co,Ni,Cu) alloy particles with
      sizes of about 5 nm have been studied by in situ high-energy x-ray diffraction
      while subjected to oxidizing (O(2)) and reducing (H(2)) gas atmospheres at
      elevated temperatures. The different gas atmospheres do not affect substantially
      the random alloy, face-centered-cubic structure type of the particles but do
      affect the way the metal atoms pack together. In an O(2) atmosphere, atoms get
      extra separated from each other, whereas, in an H(2) atmosphere, they come closer
      together. The effect is substantial, amounting to 0.1 A difference in the first
      neighbor atomic distances, and concurs with a dramatic change of the particle
      catalytic properties. It is argued that such reactive gas induced "expansion
      shrinking" is a common phenomenon that may be employed for the engineering of
      "smart" nanoparticles responding advantageously to envisaged gas environments.

PMID- 23005960
TI  - Evolution of shock-induced orientation-dependent metastable states in crystalline
      aluminum.
AB  - The evolution of orientation-dependent metastable states during shock-induced
      solid-liquid phase transitions in crystalline Al is followed using moving window
      molecular dynamics simulations. The orientation-dependent transition pathways
      towards an orientation-independent final state Hugoniot include both "cold
      melting" followed by recrystallization in [110]- and [111]-oriented shock waves
      and crystal overheating followed by melting in [100] shock waves. The orientation
      dependent dynamics take place within a zone that can extend up to hundreds of
      nanometers behind the shock front.

PMID- 23005961
TI  - Better alloys with quantum design.
AB  - Alloy discovery and development is slowed by trial and error methods used to
      identify beneficial alloying elements. This fact has led to suggestions that
      integrating quantum theory and modeling with traditional experimental approaches
      might accelerate the pace of alloy discovery. We report here on one such effort,
      using advances in first principles computation along with an evolving theory that
      allows for the partitioning of charge density into chemically meaningful
      structures, alloying elements that improve the adhesive properties of interfaces
      common to high strength steels have been identified.

PMID- 23005962
TI  - Critical role of two-dimensional island-mediated growth on the formation of
      semiconductor heterointerfaces.
AB  - We experimentally demonstrate a sigmoidal variation of the composition profile
      across semiconductor heterointerfaces. The wide range of material systems (III
      arsenides, III-antimonides, III-V quaternary compounds, III-nitrides) exhibiting
      such a profile suggests a universal behavior. We show that sigmoidal profiles
      emerge from a simple model of cooperative growth mediated by two-dimensional
      island formation, wherein cooperative effects are described by a specific
      functional dependence of the sticking coefficient on the surface coverage.
      Experimental results confirm that, except in the very early stages, island growth
      prevails over nucleation as the mechanism governing the interface development and
      ultimately determines the sigmoidal shape of the chemical profile in these two
      dimensional-grown layers. In agreement with our experimental findings, the model
      also predicts a minimum value of the interfacial width, with the minimum
      attainable value depending on the chemical identity of the species.

PMID- 23005963
TI  - Spin-dependent on-site electron correlations and localization in itinerant
      ferromagnets.
AB  - Spin selectivity in angle-resolved Auger photoelectron coincidence spectroscopy
      (AR-APECS) is used to probe electron correlation in ferromagnetic thin films. In
      particular, exploiting the AR-APECS capability to discriminate Auger electron
      emission events characterized by valence hole pairs created either in the high or
      in the low total spin state, a strong correlation effect in the Fe M(2,3)VV Auger
      line shape (measured in coincidence with the Fe 3p photoelectrons) of Fe/Cu(001)
      thin films is detected and ascribed to interactions within the majority spin
      subband. Such an assignment follows from a close comparison of the experimental
      AR-APECS line shapes with the predictions of a model based on spin polarized
      density functional theory and the Cini-Sawatzky approach.

PMID- 23005964
TI  - Antiferromagnetism in the Hubbard model on the Bernal-stacked honeycomb bilayer.
AB  - Using a combination of quantum Monte Carlo simulations, functional
      renormalization group calculations and mean-field theory, we study the Hubbard
      model on the Bernal-stacked honeycomb bilayer at half-filling as a model system
      for bilayer graphene. The free bands consisting of two Fermi points with
      quadratic dispersions lead to a finite density of states at the Fermi level,
      which triggers an antiferromagnetic instability that spontaneously breaks
      sublattice and spin rotational symmetry once local Coulomb repulsions are
      introduced. Our results reveal an inhomogeneous participation of the spin moments
      in the ordered ground state, with enhanced moments at the threefold coordinated
      sites. Furthermore, we find the antiferromagnetic ground state to be robust with
      respect to enhanced interlayer couplings and extended Coulomb interactions.

PMID- 23005965
TI  - Electrical manipulation of Majorana fermions in an interdigitated superconductor
      ferromagnet device.
AB  - We show that a topological phase supporting Majorana fermions can form in a two
      dimensional electron gas (2DEG) adjacent to an interdigitated superconductor
      ferromagnet structure. An advantage of this setup is that the 2DEG can induce the
      required Zeeman splitting and superconductivity from a single interface, allowing
      one to utilize a wide class of 2DEGs including the surface states of bulk InAs.
      We demonstrate that the interdigitated device supports a robust topological phase
      when the finger spacing lambda is smaller than half of the Fermi wavelength
      lambda(F). In this regime, the electrons effectively see a "smeared" Zeeman
      splitting and pairing field despite the interdigitation. The topological phase
      survives even in the opposite limit lambda > lambda(F)/2, although with a reduced
      bulk gap. We describe how to electrically generate a vortex in this setup to trap
      a Majorana mode, and predict an anomalous Fraunhofer pattern that provides a
      sharp signature of chiral Majorana edge states.

PMID- 23005966
TI  - Dimensional-crossover-driven Mott transition in the frustrated Hubbard model.
AB  - We study the Mott transition in a frustrated Hubbard model with next-nearest
      neighbor hopping at half-filling. The interplay between interaction,
      dimensionality, and geometric frustration closes the one-dimensional Mott gap and
      gives rise to a metallic phase with Fermi surface pockets. We argue that they
      emerge as a consequence of remnant one-dimensional umklapp scattering at the
      momenta with vanishing interchain hopping matrix elements. In this pseudogap
      phase, enhanced d-wave pairing correlations are driven by antiferromagnetic
      fluctuations. Within the adopted cluster dynamical mean-field theory on the 8 * 2
      cluster and down to our lowest temperatures, the transition from one to two
      dimensions is continuous.

PMID- 23005967
TI  - Peierls distortion and quantum solitons.
AB  - Peierls distortion and quantum solitons are two hallmarks of 1-dimensional
      condensed-matter systems. Here we propose a quantum model for a one-dimensional
      system of nonlinearly interacting electrons and phonons, where the phonons are
      represented via coherent states. This model permits a unified description of
      Peierls distortion and quantum solitons. The nonlinear electron-phonon
      interaction and the resulting deformed symmetry of the Hamiltonian are
      distinctive features of the model, of which that of Su, Schrieffer, and Heeger
      can be regarded as a special case.

PMID- 23005968
TI  - Luttinger-liquid universality in the time evolution after an interaction quench.
AB  - We provide evidence that the relaxation dynamics of one-dimensional, metallic
      Fermi systems resulting out of an abrupt amplitude change of the two-particle
      interaction has aspects which are universal in the Luttinger liquid sense: the
      leading long-time behavior of certain observables is described by universal
      functions of the equilibrium Luttinger liquid parameter and the renormalized
      velocity. We analytically derive those functions for the Tomonaga-Luttinger model
      and verify our hypothesis of universality by considering spinless lattice
      fermions within the framework of the density-matrix renormalization group.

PMID- 23005969
TI  - Electron-phonon coupling in crystalline organic semiconductors: microscopic
      evidence for nonpolaronic charge carriers.
AB  - We consider electron-phonon coupling in crystalline organic semiconductors, using
      naphthalene for our case study. Employing a first-principles approach, we compute
      the changes in the selfconsistent Kohn-Sham potential corresponding to different
      phonon modes and go on to obtain the carrier-phonon coupling matrix elements
      (vertex functions). We then evaluate perturbatively the quasiparticle spectral
      residues for electrons at the bottom of the lowest unoccupied (LUMO), and holes
      at the top of the highest occupied (HOMO), band, obtaining Z(e) ~ 0.74 and Z(h) ~
      0.78, respectively. Along with the widely accepted notion that the carrier-phonon
      coupling strengths in polyacenes decrease with increasing molecular size, our
      results provide strong microscopic evidence for the previously conjectured
      nonpolaronic nature of bandlike carriers in these systems.

PMID- 23005970
TI  - Low-energy models for correlated materials: bandwidth renormalization from
      Coulombic screening.
AB  - We provide a prescription for constructing Hamiltonians representing the low
      energy physics of correlated electron materials with dynamically screened Coulomb
      interactions. The key feature is a renormalization of the hopping and
      hybridization parameters by the processes that lead to the dynamical screening.
      The renormalization is shown to be non-negligible for various classes of
      correlated electron materials. The bandwidth reduction effect is necessary for
      connecting models to materials behavior and for making quantitative predictions
      for low-energy properties of solids.

PMID- 23005971
TI  - Angle-dependent van Hove singularities in a slightly twisted graphene bilayer.
AB  - Recent studies show that two low-energy van Hove singularities (VHSs) seen as two
      pronounced peaks in the density of states could be induced in a twisted graphene
      bilayer. Here, we report angle-dependent VHSs of a slightly twisted graphene
      bilayer studied by scanning tunneling microscopy and spectroscopy. We show that
      energy difference of the two VHSs follows DeltaE(vhs)~hnu(F)DeltaK between 1.0
      degrees  and 3.0 degrees  [here nu(F)~1.1 * 10(6) m/s is the Fermi velocity of
      monolayer graphene, and DeltaK = 2Ksin(theta/2) is the shift between the
      corresponding Dirac points of the twisted graphene bilayer]. This result
      indicates that the rotation angle between graphene sheets does not result in a
      significant reduction of the Fermi velocity, which quite differs from that
      predicted by band structure calculations. However, around a twisted angle
      theta~1.3 degrees , the observed DeltaE(vhs)~0.11 eV is much smaller than the
      expected value hnu(F)DeltaK~0.28 eV at 1.3 degrees . The origin of the reduction
      of DeltaE(vhs) at 1.3 degrees  is discussed.

PMID- 23005972
TI  - Spin texture readout of a moore-read topological quantum register.
AB  - We study the composite charged spin texture (CST) over the Moore-Read quantum
      Hall state that arises when a collection of elementary CSTs is moved to the same
      location. Following an algebraic approach based on the characteristic pair
      correlations of the Moore-Read state, we find that the spin texture associated
      with a composite CST is set by the fusion sector of the underlying non-Abelian
      quasiparticles. This phenomenon provides a novel way to read out the quantum
      register of a non-Abelian topologically ordered phase.

PMID- 23005973
TI  - Inducing an incipient terahertz finite plasmonic crystal in coupled two
      dimensional plasmonic cavities.
AB  - We measured a change in the current transport of an antenna-coupled, multigate,
      GaAs/AlGaAs field-effect transistor when terahertz electromagnetic waves
      irradiated the transistor and attribute the change to bolometric heating of the
      electrons in the two dimensional electron channel. The observed terahertz
      absorption spectrum indicates coherence between plasmons excited under adjacent
      biased device gates. The experimental results agree quantitatively with a
      theoretical model we developed that is based on a generalized plasmonic
      transmission line formalism and describes an evolution of the plasmonic spectrum
      with increasing electron density modulation from homogeneous to the crystal
      limit. These results demonstrate an electronically induced and dynamically
      tunable plasmonic band structure.

PMID- 23005974
TI  - Quantum Hall to charge-density-wave phase transitions in ABC-trilayer graphene.
AB  - ABC-stacked trilayer graphene's chiral band structure results in three (n=0, 1,
      2) Landau level orbitals with zero kinetic energy. This unique feature has
      important consequences on the interaction-driven states of the 12-fold degenerate
      (including spin and valley) N=0 Landau level. In particular, at many filling
      factors nu(T) = +/-5, +/-4, +/-2, +/-1 a quantum phase transition from a quantum
      Hall liquid state to a triangular charge-density wave occurs as a function of the
      single particle-induced Landau level orbital splitting Delta(LL). Experimental
      signatures of this phase transition are also discussed.

PMID- 23005975
TI  - Coulomb gap triptych in a periodic array of metal nanocrystals.
AB  - The Coulomb gap in the single-particle density of states (DOS) is a universal
      consequence of electron-electron interaction in disordered systems with localized
      electron states. Here we show that in arrays of monodisperse metallic
      nanocrystals, there is not one but three identical adjacent Coulomb gaps, which
      together form a structure that we call a "Coulomb gap triptych." We calculate the
      DOS and the conductivity in two- and three-dimensional arrays using a computer
      simulation. Unlike in the conventional Coulomb glass models, in nanocrystal
      arrays the DOS has a fixed width in the limit of large disorder. The Coulomb gap
      triptych can be studied via tunneling experiments.

PMID- 23005976
TI  - Cloaking core-shell nanoparticles from conducting electrons in solids.
AB  - In this Letter, we aim at making nanoparticles embedded in a host semiconductor
      with a size comparable to electronic wavelengths "invisible" to the electron
      transport. Inspired by the recent progress made in optics and working within the
      framework of the expansion of partial waves, we demonstrate that the opposite
      effects imposed by potential barriers and wells of a core-shell nanoparticle on
      the phase shifts associated with the scattered electron wave could make the
      scattering cross section of the first two partial waves vanish simultaneously. We
      show that this is sufficient to cloak the nanoparticle from being detected by
      electrons with specific energy in the sense that a total scattering cross section
      smaller than 0.01% of the physical cross section can be obtained and a 4 orders
      of magnitude difference in the total scattering cross section can be presented
      within an energy range of only 40 meV, indicating possible applications of the
      "electron cloaks" as novel electronic switches and sensors, and in efficient
      energy harvesting and conversion technologies.

PMID- 23005977
TI  - Surface adatom conductance filtering in scanning tunneling spectroscopy of co
      doped BaFe2As2 iron pnictide superconductors.
AB  - We establish in a combination of ab initio theory and experiments that the
      tunneling process in scanning tunneling microscopy or spectroscopy on the A-122
      iron pnictide superconductors-in this case BaFe(2-x)Co(x)As(2)-involves a strong
      adatom filtering of the differential conductance from the near-E(F) Fe-3d states,
      which in turn originates from the topmost subsurface Fe layer of the crystal. The
      calculations show that the dominance of surface Ba-related tunneling pathways
      leaves fingerprints found in the experimental differential conductance data,
      including large particle-hole asymmetry and energy-dependent contrast inversion
      in conductance maps.

PMID- 23005978
TI  - From incommensurate correlations to mesoscopic spin resonance in YbRh2Si2.
AB  - Spin fluctuations are reported near the magnetic field-driven quantum critical
      point in YbRh(2)Si(2). On cooling, ferromagnetic fluctuations evolve into
      incommensurate correlations located at q(0) = +/-(delta,delta), with delta = 0.14
      +/- 0.04 r.l.u. At low temperatures, an in-plane magnetic field induces a sharp
      intradoublet resonant excitation at an energy E(0) = gMU(B)MU(0)H with g = 3.8 +/
      0.2. The intensity is localized at the zone center, indicating precession of
      spin density extending xi = 6 +/- 2 A beyond the 4f site.

PMID- 23005979
TI  - Penetration depth of transverse spin current in ultrathin ferromagnets.
AB  - We report a novel depth dependence for the penetration of spin current into
      ultrathin ferromagnets. Ferromagnetic resonance measurements show that transverse
      spin current pumped into three structurally distinct ferromagnets is attenuated,
      on reflection, by an amount proportional to the ferromagnetic layer thickness,
      saturating abruptly at 1.2 +/- 0.1 nm. The observed power-law decay, differing
      significantly from the (exponential) characteristic-length dependence for
      longitudinal spin current, confirms models of spin momentum transfer which have
      been inaccessible to experiment.

PMID- 23005980
TI  - Magnetic soft modes in the distorted triangular antiferromagnet alpha-CaCr2O4.
AB  - In this Letter, we explore the phase diagram and excitations of a distorted
      triangular lattice antiferromagnet. The unique two-dimensional distortion
      considered here is very different from the "isosceles"-type distortion that has
      been extensively investigated. We show that it is able to stabilize a 120 degrees
      spin structure for a large range of exchange interaction values, while new
      structures are found for extreme distortions. A physical realization of this
      model is alpha-CaCr(2)O(4), which has a 120 degrees  structure but lies very
      close to the phase boundary. This is verified by inelastic neutron scattering
      which reveals unusual rotonlike minima at reciprocal space points different from
      those corresponding to the magnetic order.

PMID- 23005981
TI  - Ultrafast magnetic vortex core switching driven by the topological inverse
      Faraday effect.
AB  - We present a theoretical discovery of an unconventional mechanism of inverse
      Faraday effect which acts selectively on topological magnetic structures. The
      effect, topological inverse Faraday effect, is induced by the spin Berry's phase
      of the magnetic structure when a circularly polarized light is applied. Thus a
      spin-orbit interaction is not necessary unlike that in the conventional inverse
      Faraday effect. We demonstrate by numerical simulation that topological inverse
      Faraday effect realizes ultrafast switching of a magnetic vortex within a
      switching time of 150 ps without magnetic field.

PMID- 23005982
TI  - Incommensurate orbital modulation behind ferroelectricity in CuFeO2.
AB  - CuFeO(2) is one of the multiferroic materials and is the first case that the
      electric polarization is not explained by the magnetostriction model or the spin
      current model. We have studied this material using soft x-ray resonant
      diffraction and found that superlattice reflection 0 1-2q 0 appears in the
      ferroelectric and incommensurate magnetic ordered phase at the Fe L(2,3)
      absorption edges and moreover that the rotation of the x-ray polarization such as
      from sigma to pi or from pi to sigma is allowed at this reflection. These
      findings definitely provide direct evidence that the 3d t(2g?) orbital state of
      Fe ions has a long-range order in the ferroelectric state. The spin-orbit
      interaction in Fe ions plays a crucial role to the ferroelectricity in CuFeO(2),
      coupling two nontrivial spin and orbital orders, both of which break the crystal
      symmetry.

PMID- 23005983
TI  - Asymmetric thermal line shape broadening in a gapped 3D antiferromagnet: evidence
      for strong correlations at finite temperature.
AB  - It is widely believed that magnetic excitations become increasingly incoherent as
      the temperature is raised due to random collisions which limit their lifetime.
      This picture is based on spin-wave calculations for gapless magnets in 2 and 3
      dimensions and is observed experimentally as a symmetric Lorentzian broadening in
      energy. Here, we investigate a three-dimensional dimer antiferromagnet and find
      unexpectedly that the broadening is asymmetric-indicating that far from thermal
      decoherence, the excitations behave collectively like a strongly correlated gas.
      This result suggests that a temperature activated coherent state of
      quasiparticles is not confined to special cases like the highly dimerized spin
      1/2 chain but is found generally in dimerized antiferromagnets of all
      dimensionalities and perhaps gapped magnets in general.

PMID- 23005984
TI  - d0 ferromagnetic interface between nonmagnetic perovskites.
AB  - We use computational and experimental methods to study d(0) ferromagnetism at a
      charge-imbalanced interface between two perovskites. In SrTiO(3)/KTaO(3)
      superlattice calculations, the charge imbalance introduces holes in the SrTiO(3)
      layer, inducing a d(0) ferromagnetic half-metallic 2D hole gas at the interface
      oxygen 2p orbitals. The charge imbalance overrides doping by vacancies at
      realistic concentrations. Varying the constituent materials shows ferromagnetism
      to be a general property of hole-type d(0) perovskite interfaces. Atomically
      sharp epitaxial d(0) SrTiO(3)/KTaO(3), SrTiO(3)/KNbO(3), and SrTiO(3)/NaNbO(3)
      interfaces are found to exhibit ferromagnetic hysteresis at room temperature. We
      suggest that the behavior is due to the high density of states and exchange
      coupling at the oxygen t(1g) band in comparison with the more studied d band
      t(2g) symmetry electron gas.

PMID- 23005985
TI  - Measurement of intrinsic dirac fermion cooling on the surface of the topological
      insulator Bi2Se3 using time-resolved and angle-resolved photoemission
      spectroscopy.
AB  - We perform time- and angle-resolved photoemission spectroscopy of a prototypical
      topological insulator (TI) Bi(2)Se(3) to study the ultrafast dynamics of surface
      and bulk electrons after photoexcitation. By analyzing the evolution of surface
      states and bulk band spectra, we obtain their electronic temperature and chemical
      potential relaxation dynamics separately. These dynamics reveal strong phonon
      assisted surface-bulk coupling at high lattice temperature and total suppression
      of inelastic scattering between the surface and the bulk at low lattice
      temperature. In this low temperature regime, the unique cooling of Dirac fermions
      in TI by acoustic phonons is manifested through a power law dependence of the
      surface temperature decay rate on carrier density.

PMID- 23005986
TI  - Possible quantum diffusion of polaronic muons in Dy(2)Ti(2)O(7) spin ice.
AB  - We interpret recent measurements of the zero field muon relaxation rate in the
      magnetic pyrochlore Dy(2)Ti(2)O(7) as resulting from the quantum diffusion of
      muons in the material. In this scenario, the plateau observed at low temperature
      (< 7 K) in the relaxation rate is due to coherent tunneling of muons through a
      spatially disordered spin state and not to any magnetic fluctuations persisting
      at low temperature. Two further regimes either side of a maximum relaxation rate
      at T* = 50 K correspond to a crossover between tunneling and incoherent activated
      hopping motion of the muon. Our fit of the experimental data is compared with the
      case of muonium diffusion in KCl.

PMID- 23005987
TI  - Evolutionary optimization of optical antennas.
AB  - The design of nanoantennas has so far been mainly inspired by radio-frequency
      technology. However, the material properties and experimental settings need to be
      reconsidered at optical frequencies, which would entail the need for alternative
      optimal antenna designs. Here we subject a checkerboard-type, initially random
      array of gold cubes to evolutionary optimization. To illustrate the power of the
      approach, we demonstrate that by optimizing the near-field intensity enhancement,
      the evolutionary algorithm finds a new antenna geometry, essentially a split-ring
      two-wire antenna hybrid that surpasses by far the performance of a conventional
      gap antenna by shifting the n=1 split-ring resonance into the optical regime.

PMID- 23005988
TI  - Nonuniformities in the angle of repose and packing fraction of large heaps of
      particles.
AB  - We report a numerical investigation of the structural properties of very large
      three-dimensional heaps of particles produced by ballistic deposition from
      extended circular dropping areas. Very large heaps are found to contain three new
      geometrical characteristics not observed before: they may have two external
      angles of repose, an internal angle of repose, and four distinct packing fraction
      (density) regions. Such characteristics are shown to be directly correlated with
      the size of the dropping zone. In addition, we also describe how noise during the
      deposition affects the final heap structure.

PMID- 23005989
TI  - Anomalous stress profile in a sheared granular column.
AB  - We present measurements of the stress as a function of vertical position in a
      column of granular material sheared in a cylindrical Couette device. All three
      components of the stress tensor on the outer cylinder were measured as a function
      of distance from the free surface at shear rates low enough that the material was
      in the dense, slow flow regime. We find that the stress profile differs
      fundamentally from that of fluids, from the predictions of plasticity theories,
      and from intuitive expectation. We argue that the anomalous stress profile is due
      to an anisotropic fabric caused by the combined action of gravity and shear.

PMID- 23005990
TI  - Direct and indirect electron emission from the green fluorescent protein
      chromophore.
AB  - Photoelectron spectra of the deprotonated green fluorescent protein chromophore
      have been measured in the gas phase at several wavelengths within and beyond the
      S(0)-S(1) photoabsorption band of the molecule. The vertical detachment energy
      (VDE) was determined to be 2.68 +/- 0.1 eV. The data show that the first
      electronically excited state is bound in the Franck-Condon region, and that
      electron emission proceeds through an indirect (resonant) electron-emission
      channel within the corresponding absorption band.

PMID- 23005991
TI  - Physical origin of anharmonic dynamics in proteins: new insights from resolution
      dependent neutron scattering on homomeric polypeptides.
AB  - Neutron scattering reveals a complex dynamics in polypeptide chains, with two
      main onsets of anharmonicity whose physical origin and biological role are still
      debated. In this study the dynamics of strategically selected homomeric
      polypeptides is investigated with elastic neutron scattering using different
      energy resolutions and compared with that of a real protein. Our data spotlight
      the dependence of anharmonic transition temperatures and fluctuation amplitudes
      on energy resolution, which we quantitatively explain in terms of a two-site
      model for the protein-hydration water energy landscape. Experimental data
      strongly suggest that the protein dynamical transition is not a mere resolution
      effect but is due to a real physical effect. Activation barriers and free energy
      values obtained for the protein dynamical transition allow us to make a
      connection with the two-well interaction potential of supercooled-confined water
      proposed to explain a low-density->high-density liquid-liquid transition.

PMID- 23005992
TI  - Hierarchical helical order in the twisted growth of plant organs.
AB  - The molecular and cellular basis of left-right asymmetry in plant morphogenesis
      is a fundamental issue in biology. A rapidly elongating root or hypocotyl of
      twisting mutants of Arabidopsis thaliana exhibits a helical growth with a
      handedness opposite to that of the underlying cortical microtubule arrays in
      epidermal cells. However, how such a hierarchical helical order emerges is
      currently unknown. We propose a model for investigating macroscopic chiral
      asymmetry in Arabidopsis mutants. Our elastic model suggests that the helical
      pattern observed is a direct consequence of the simultaneous presence of
      anisotropic growth and tilting of cortical microtubule arrays. We predict that
      the root helical pitch angle is a function of the microtubule helical angle and
      elastic moduli of the tissues. The proposed model is versatile and is potentially
      important for other biological systems ranging from protein fibrous structures to
      tree trunks.

PMID- 23005993
TI  - Optimal shapes of surface slip driven self-propelled microswimmers.
AB  - We study the efficiency of self-propelled swimmers at low Reynolds numbers,
      assuming that the local energetic cost of maintaining a propulsive surface slip
      velocity is proportional to the square of that velocity. We determine numerically
      the optimal shape of a swimmer such that the total power is minimal while
      maintaining the volume and the swimming speed. The resulting shape depends
      strongly on the allowed maximum curvature. When sufficient curvature is allowed
      the optimal swimmer exhibits two protrusions along the symmetry axis. The results
      show that prolate swimmers such as Paramecium have an efficiency that is ~20%
      higher than that of a spherical body, whereas some microorganisms have shapes
      that allow even higher efficiency.

PMID- 23005994
TI  - Optimized cross-slot flow geometry for microfluidic extensional rheometry.
AB  - A precision-machined cross-slot flow geometry with a shape that has been
      optimized by numerical simulation of the fluid kinematics is fabricated and used
      to measure the extensional viscosity of a dilute polymer solution. Full-field
      birefringence microscopy is used to monitor the evolution and growth of
      macromolecular anisotropy along the stagnation point streamline, and we observe
      the formation of a strong and uniform birefringent strand when the dimensionless
      flow strength exceeds a critical Weissenberg number Wi(crit) ~ 0.5. Birefringence
      and bulk pressure drop measurements provide self-consistent estimates of the
      planar extensional viscosity of the fluid over a wide range of deformation rates
      (26 s(-1) <= epsilon <= 435 s(-1)) and are also in close agreement with numerical
      simulations performed by using a finitely extensible nonlinear elastic dumbbell
      model.

PMID- 23005995
TI  - Switching between crystallization and amorphous agglomeration of alkyl thiol
      coated gold nanoparticles.
AB  - Crystalline and amorphous materials composed of the same atoms exhibit strikingly
      different properties. Likewise, the behavior of materials composed of mesoscale
      particles depends on the arrangement of their constituent particles. Here, we
      demonstrate control over particle arrangement during agglomeration. We obtain
      disordered and ordered agglomerates of the same alkyl thiol-coated gold
      nanoparticles depending on temperature and solvent. We find that ordered
      agglomeration occurs exclusively above the melting temperature of the ligand
      shells. Many-particle simulations show that the contact mechanics of the ligand
      shells dominate the order-disorder transition: Purely spherical particle-particle
      interactions yield order, whereas localized "stiction" between the ligand shells
      leads to disorder. This indicates that the "stickiness" and the packing of the
      agglomerates can be switched by the state of the ligand shells. It suggests that
      contact mechanics govern ordering in a wide range of nanoparticles.

PMID- 23005996
TI  - Self-similarity and energy dissipation in stepped polymer films.
AB  - The surface of a thin liquid film with a nonconstant curvature is unstable, as
      the Laplace pressure drives a flow mediated by viscosity. We present the results
      of experiments on one of the simplest variable curvature surfaces: a thin polymer
      film with a step. Height profiles are measured as a function of time for a
      variety of molecular weights. The evolution of the profiles is shown to be self
      similar. This self-similarity offers a precise measurement of the capillary
      velocity by comparison with numerical solutions of the thin film equation. We
      also derive a master expression for the time dependence of the excess free energy
      as a function of the material properties and film geometry. The experiment and
      theory are in excellent agreement and indicate the effectiveness of stepped
      polymer films to elucidate nanoscale rheological properties.

PMID- 23005997
TI  - Sizes of multilamellar vesicles in shear.
AB  - The dynamics of the multilamellar vesicle (MLV) is analyzed theoretically, where
      membrane interaction squeezes the solvent to flow between the neighboring
      membranes. With the applied affine shear, the dynamic free energy density of the
      MLV develops a minima, which selects the MLV size. The model predicts a terminal
      shear rate, below which the metastable MLV exists. The scaling relations for the
      MLV size and the terminal shear are both consistent with the experiments.

PMID- 23005998
TI  - Bubble driven quasioscillatory translational motion of catalytic micromotors.
AB  - A new quasioscillatory translational motion has been observed for big Janus
      catalytic micromotors with a fast CCD camera. Such motional behavior is found to
      coincide with both the bubble growth and burst processes resulting from the
      catalytic reaction, and the competition of the two processes generates a net
      forward motion. Detailed physical models have been proposed to describe the above
      processes. It is suggested that the bubble growth process imposes a growth force
      moving the micromotor forward, while the burst process induces an instantaneous
      local pressure depression pulling the micromotor backward. The theoretic
      predictions are consistent with the experimental data.

PMID- 23005999
TI  - Dynamics of ranking processes in complex systems.
AB  - The world is addicted to ranking: everything, from the reputation of scientists,
      journals, and universities to purchasing decisions is driven by measured or
      perceived differences between them. Here, we analyze empirical data capturing
      real time ranking in a number of systems, helping to identify the universal
      characteristics of ranking dynamics. We develop a continuum theory that not only
      predicts the stability of the ranking process, but shows that a noise-induced
      phase transition is at the heart of the observed differences in ranking regimes.
      The key parameters of the continuum theory can be explicitly measured from data,
      allowing us to predict and experimentally document the existence of three phases
      that govern ranking stability.

PMID- 23006000
TI  - Localization and spreading of diseases in complex networks.
AB  - Using the susceptible-infected-susceptible model on unweighted and weighted
      networks, we consider the disease localization phenomenon. In contrast to the
      well-recognized point of view that diseases infect a finite fraction of vertices
      right above the epidemic threshold, we show that diseases can be localized on a
      finite number of vertices, where hubs and edges with large weights are centers of
      localization. Our results follow from the analysis of standard models of networks
      and empirical data for real-world networks.

PMID- 23006001
TI  - Transport on coupled spatial networks.
AB  - Transport processes on spatial networks are representative of a broad class of
      real world systems which, rather than being independent, are typically
      interdependent. We propose a measure of utility to capture key features that
      arise when such systems are coupled together. The coupling is defined in a way
      that is not solely topological, relying on both the distribution of sources and
      sinks, and the method of route assignment. Using a toy model, we explore relevant
      cases by simulation. For certain parameter values, a picture emerges of two
      regimes. The first occurs when the flows go from many sources to a small number
      of sinks. In this case, network utility is largest when the coupling is at its
      maximum and the average shortest path is minimized. The second regime arises when
      many sources correspond to many sinks. Here, the optimal coupling no longer
      corresponds to the minimum average shortest path, as the congestion of traffic
      must also be taken into account. More generally, results indicate that coupled
      spatial systems can give rise to behavior that relies subtly on the interplay
      between the coupling and randomness in the source-sink distribution.

PMID- 23006004
TI  - Does adolescents' disclosure to their parents matter for their academic
      adjustment?
AB  - The role of adolescents' disclosure to their parents in their academic adjustment
      was examined in a study of 825 American and Chinese adolescents (mean age = 12.73
      years). Four times over the seventh and eighth grades, adolescents reported on
      their spontaneous disclosure of everyday activities to their parents, the quality
      of their relationships with their parents, and their parents' autonomy support
      and control. Information about multiple dimensions of adolescents' academic
      adjustment (e.g., learning strategies, autonomous vs. controlled motivation, and
      grades) was also obtained. Both American and Chinese adolescents' disclosure
      predicted their enhanced academic adjustment over time. However, when American
      adolescents disclosed in a negative context (e.g., a poor parent-child
      relationship or controlling parenting), their autonomous (vs. controlled)
      motivation was undermined.

PMID- 23006002
TI  - Design, synthesis, and pharmacological evaluation of piperidin-4-yl amino aryl
      sulfonamides: novel, potent, selective, orally active, and brain penetrant 5-HT6
      receptor antagonists.
AB  - Our initial findings around aryl sulfonamide series led to N-(3,5-dichloro-2
      methoxyphenyl)-3-(1-methylpiperidin-4-ylamino)-4-methoxy benzenesulfonamide as
      potent and selective 5-HT(6) receptor (5-HT(6)R) antagonist with reasonable
      pharmacokinetic properties and activity in animal models of cognition. However,
      lack of brain penetration and P-glycoprotein liability makes this scaffold
      unsuitable for further development. Our goal was to identify small molecule 5
      HT(6)R antagonist with adequate brain penetration, acceptable ADME properties, no
      P-glycoprotein, and no hERG liability. Several structural modifications including
      bringing conformational constraint around the sulfonamide -NH group and
      introduction of a heteroatom to modulate the physicochemical properties were
      attempted. This effort culminated in the discovery of series of novel, potent,
      selective, orally bioavailable, and adequately brain penetrant compounds with no
      hERG liability. These compounds showed activity in animal models of cognition
      like object recognition task and water maze and in brain microdialysis studies at
      lower doses.

PMID- 23006005
TI  - Colloidal photonic crystals with narrow stopbands assembled from low-adhesive
      superhydrophobic substrates.
AB  - This article presents a facile approach to centimeter-scale colloidal photonic
      crystals (PCs) with narrow stopbands assembled on low-adhesive superhydrophobic
      substrates. The full-width-at-half-maxima of the stopbands are just 12 nm. The
      narrow stopbands of colloidal PCs are ascribed to the combined effects of
      perfectly ordered assembly structure, large-scale crack elimination, decreased
      void fraction, and sufficient thickness of the colloidal PCs. These properties
      result from a self-assembly process on a low-adhesive superhydrophobic substrate.
      Latex suspension on this substrate displays a receding three-phase contact line
      during evaporation, which releases tensile stress induced by latex shrinkage and
      results in complete elimination of cracks in the colloidal PCs. Furthermore, the
      simultaneous assembly of latex particles on the outermost layer of a spread
      liquid film contributes to the perfectly ordered assembly structure. This facile
      fabrication of centimeter-scale colloidal PCs with narrow stopbands will offer
      significant insights into the design and creation of novel optical devices.

PMID- 23006009
TI  - Retraction. Development, validity and reliability of the Turkish version of the
      Hung Postpartum Stress Scale.

PMID- 23006008
TI  - Internalized stigma and HIV status disclosure among HIV-positive black men who
      have sex with men.
AB  - Black men who have sex with men (BMSM) are severely affected by the HIV epidemic,
      yet research on the relationship between HIV stigma and status disclosure is
      relatively limited among this population. Within this epidemic, internalized HIV
      stigma, the extent to which people living with HIV/AIDS endorse the negative
      beliefs associated with HIV as true of themselves, can negatively shape
      interpersonal outcomes and have important implications for psychological and
      physical health. In a sample of HIV-positive BMSM (N=156), the current study
      examined the effect of internalized stigma on HIV status disclosure to sexual
      partners, which can inform sexual decision-making in serodiscordant couples, and
      HIV status disclosure to family members, which can be beneficial in minimizing
      the psychological distress associated with HIV. Results revealed that greater
      internalized stigma was associated with less HIV status disclosure to
      participants' last sexual partner and to family members. Findings from this study
      provide evidence that internalized negative beliefs about one's HIV status are
      linked to adverse interpersonal consequences. Implications of these findings are
      discussed with regard to prevention and intervention efforts to reduce HIV
      stigmatization.

PMID- 23006010
TI  - Estimating diagnostic accuracy of raters without a gold standard by exploiting a
      group of experts.
AB  - In diagnostic medicine, estimating the diagnostic accuracy of a group of raters
      or medical tests relative to the gold standard is often the primary goal. When a
      gold standard is absent, latent class models where the unknown gold standard test
      is treated as a latent variable are often used. However, these models have been
      criticized in the literature from both a conceptual and a robustness perspective.
      As an alternative, we propose an approach where we exploit an imperfect reference
      standard with unknown diagnostic accuracy and conduct sensitivity analysis by
      varying this accuracy over scientifically reasonable ranges. In this article, a
      latent class model with crossed random effects is proposed for estimating the
      diagnostic accuracy of regional obstetrics and gynaecological (OB/GYN) physicians
      in diagnosing endometriosis. To avoid the pitfalls of models without a gold
      standard, we exploit the diagnostic results of a group of OB/GYN physicians with
      an international reputation for the diagnosis of endometriosis. We construct an
      ordinal reference standard based on the discordance among these international
      experts and propose a mechanism for conducting sensitivity analysis relative to
      the unknown diagnostic accuracy among them. A Monte Carlo EM algorithm is
      proposed for parameter estimation and a BIC-type model selection procedure is
      presented. Through simulations and data analysis we show that this new approach
      provides a useful alternative to traditional latent class modeling approaches
      used in this setting.

PMID- 23006011
TI  - Advantages of atmospheric pressure chemical ionization in gas chromatography
      tandem mass spectrometry: pyrethroid insecticides as a case study.
AB  - Gas chromatography coupled to mass spectrometry (GC/MS) has been extensively
      applied for determination of volatile, nonpolar, compounds in many applied fields
      like food safety, environment, or toxicology. The wide majority of methods
      reported use electron ionization (EI), which may result in extensive
      fragmentation of analytes compromising selectivity and sensitivity. This might
      also complicate the application of tandem MS due to lack of specific/abundant
      precursor ions. Pyrethroids are examples of compounds with this behavior. In this
      work, the potential of atmospheric pressure chemical ionization (APCI), a softer
      form of ionization, combined with GC and a triple quadrupole mass analyzer was
      investigated, taking pyrethroids as a case study and their determination in fruit
      and vegetables as example application. Ionization and fragmentation behavior of
      eight pyrethroids (bifenthrin, cyfluthrin, cypermethrin, permethrin, lambda
      cyhalothrin, fluvalinate, fenvalerate, and deltamethrin) by APCI were studied.
      The formation of a highly abundant (quasi) molecular ion was the main goal
      because of the enhanced selectivity when used as precursor ion in tandem MS. The
      addition of water as a modifier was tested to promote the generation of
      protonated molecules, resulting in notable improvement of sensitivity and
      selectivity for most compounds. The excellent detectability (low detection limits
      (LODs) <20 fg achieved) when using APCI combined with state-of-the-art tandem MS
      was demonstrated for real samples. Additionally, matrix effects were evaluated in
      terms of signal enhancement/suppression. Depending on the matrix, different
      degrees of suppression were observed, on average reducing the signal in matrix to
      55% of that in solvent. The results presented in this paper demonstrate the
      potential of APCI as new source for GC/MS that could be applied to other
      analytical problems apart from those illustrated in this work.

PMID- 23006012
TI  - Evidence for the role of holes in blinking: negative and oxidized CdSe/CdS dots.
AB  - Thin shell CdSe/CdS colloidal quantum dots with a small 3 nm core diameter
      exhibit typical blinking and a binary PL intensity distribution. Electrochemical
      charging with one electron suppresses the blinking. With a larger core of 5 nm,
      the blinking statistics of on and off states is identical to that of a smaller
      core but the dots also display a grey state with a finite duration time (~6 ms)
      on glass. However, the grey state disappears on the electron-accepting ZnO
      nanocrystals film. In addition, the grey state PL lifetime on glass is similar to
      the trion lifetime measured from electrochemically charged dots. Therefore, the
      grey state is assigned to the photocharged negative dots. It is concluded that a
      grey state is always present as the dots get negatively photocharged even though
      it might not be observed due to the brightness of the trion and/or the duration
      time of the negative charge. With thick shell CdSe/CdS dots under electrochemical
      control, multiple charging, up to four electrons per dot, is observed as
      sequential changes in the photoluminescence lifetime which can be described by
      the Nernst equation. The small potential increment confirms the weak electron
      confinement with the thick CdS shell. Finally, the mechanism of hole-trapping and
      surface oxidation by the hole is proposed to account for the grey state and off
      state in the blinking.

PMID- 23006013
TI  - The Million HeartsTM Initiative: how nurse practitioners can help lead.

PMID- 23006014
TI  - Assessment, management, and prevention of childhood temper tantrums.
AB  - PURPOSE: To provide an overview of normal and abnormal temper tantrum behavior as
      well as give recommendations nurse practitioners (NPs) can use in counseling
      families. DATA SOURCES: Articles were identified from the following databases:
      CINAHL, HEALTH SOURCE: Nursing/Academic edition, Medline, Social Work Abstracts,
      Social Science Abstracts, Psych INFO, Psychology and Behavioral Science
      Collection. Textbook references were also identified using Stat!Ref. CONCLUSIONS:
      Temper tantrums are one of the most common behavior problems in children.
      Although most children will have tantrums, with NPs' support and guidance in
      primary care encounters, most children will not require further intervention.
      IMPLICATIONS FOR PRACTICE: NPs caring for children will need to identify normal
      and abnormal tantrum behavior as well as rule out other causes of tantrums in
      order to help parents handle the tantrum behavior. To obtain CE credit for this
      activity, go to http://www.aanp.org and click on the CE Center. Locate the
      listing for this article and complete the post-test. Follow the instructions to
      print your CE certificate.

PMID- 23006015
TI  - The enigma of heart disease in women: new insights may precipitate diagnosis and
      improve patient outcomes.
AB  - PURPOSE: To highlight the unique pathophysiology and clinical presentation of
      ischemic heart disease in women. The article will emphasize the atypical clinical
      manifestations, reinforce the pitfalls of standard testing, and provide new
      insights into novel risk factors as well as diagnostic tools to enable earlier
      detection of disease. DATA SOURCES: An extensive review of the literature was
      conducted using Pub Med and CINAHL databases. The reference lists of applicable
      published reports were also reviewed. CONCLUSIONS: Significant evidence now
      exists to support the presence of coronary ischemia even in the absence of
      obstructive epicardial coronary occlusions. Coronary microvascular disease and/or
      endothelial dysfunction account for roughly 50% of heart disease cases in women.
      Understanding the different pathophysiologic mechanisms of coronary disease, the
      uncommon expression of symptoms, and the avoidance of over-reliance on standard
      testing to reveal disease is essential for early and accurate diagnosis.
      IMPLICATIONS FOR PRACTICE: A lack of awareness persists regarding the phenomenon
      of ischemic heart disease in women. Healthcare providers must optimize their
      understanding of these variations and implement strategies for early recognition
      and treatment. Evaluation of novel risk factors, coronary calcium screening,
      evaluation of endothelial function, and estimation of functional capacity offers
      significant advantages over traditional evaluations.

PMID- 23006016
TI  - Evidence-based practice for the busy nurse practitioner: part one: relevance to
      clinical practice and clinical inquiry process.
AB  - PURPOSE: Evidence-based practice (EBP) continues to gain momentum within health
      care. The purpose of this four-part EBP series is to provide an introductory
      overview of the EBP process, emphasizing EBP steps one through three, in order to
      assist nurse practitioners (NPs) in building EBP skills that can be integrated
      into clinical practice. The relevance of EBP to the NP's clinical practice, an
      introduction to the EBP process steps, and clinical inquiry process begin the
      series. DATA SOURCES: Scientific literature review, gray literature, and online
      evidence-based practice databases and resources. CONCLUSIONS: EBP has become
      increasingly important to NPs, yet there is evidence suggesting it is not being
      fully implemented in clinical practice. EBP is one way to keep the busy NP's
      knowledge up to date, enhance clinical judgment, and augment the existing
      provider-client decision-making process. IMPLICATIONS FOR PRACTICE: The
      principles of EBP have become the cornerstone strategy for NPs to translate
      research findings into clinical practice. Practicing in an ever-changing
      healthcare environment, NPs have a responsibility to provide their clients with
      the best available evidence, while incorporating that evidence into the provider
      client decision-making process.

PMID- 23006017
TI  - Examining the benefit of vaccinating adults against pertussis.
AB  - PURPOSE: To examine recent evidence concerning the health benefits and cost
      effectiveness of replacing a single dose of adult tetanus/diphtheria vaccine with
      a single dose of tetanus/diphtheria/pertussis (TDaP). METHODS: A review of the
      literature was conducted utilizing the databases CINAHL and Medline with the
      keywords pertussis, adult immunization, vaccination, TDaP, DTaP, and healthcare
      workers. CONCLUSIONS: Recent outbreaks of pertussis have shown that preventing
      such outbreaks through immunization of adults with a single TDaP vaccine is a
      cost-effective measure. These studies focused on hospitals and universities where
      air-borne diseases are easily spread. Four hospital studies that examined the
      financial cost of investigating and treating a pertussis outbreak were reviewed.
      Results presented offer strong evidence to support vaccinating adults with TDaP
      at their next scheduled immunization or sooner if they are frequently exposed to
      populations vulnerable to pertussis. IMPLICATIONS FOR PRACTICE: Financially,
      investigating a single case of pertussis can cost hospitals hundreds of thousands
      of dollars. This is related to the time and expense of determining who was
      exposed and the provision of preventive treatment for those exposed. Preventing
      unnecessary illness and potential mortality, especially among not yet immunized
      infants, provides a strong argument for administration of the TDaP vaccine.
      Healthcare providers should educate adults about the availability and advantages
      of TDaP immunization and encourage them to be immunized with TDaP.

PMID- 23006018
TI  - The lived experience of ovarian cancer: a phenomenological approach.
AB  - PURPOSE: To describe the lived experience of women diagnosed with ovarian cancer
      using individual interviews. DATA SOURCES: Eleven women who had been diagnosed
      with ovarian cancer within the past five years were interviewed with open-ended
      guiding questions. The narrative responses were analyzed for constitutive
      patterns and relational themes according to Diekelmann and Allen's hermeneutic
      phenomenological process. CONCLUSIONS: This phenomenological study gave voice to
      the women's experience with ovarian cancer. The following six constitutive
      patterns and associated themes emerged: (a) The Revelation, (b) Jeopardy, (c) On
      the Lookout, (d) Becoming Normal, and (e) Living Every Moment. IMPLICATIONS FOR
      PRACTICE: An understanding of the common experiences and shared meanings of women
      with ovarian cancer may contribute to earlier diagnosis and improved quality of
      life. The women identified symptoms that should generate concern when reported to
      providers, potentially leading to diagnostic testing. The experiences may also
      serve to inform the development of interventions aimed at meeting the needs of
      women diagnosed with ovarian cancer.

PMID- 23006019
TI  - Emergency contraception knowledge among nurse practitioner students.
AB  - PURPOSE: The purpose of this study was to ascertain the knowledge level of nurse
      practitioner (NP) students about emergency contraception (EC), and to explore
      attitudes about EC that may intersect with willingness to prescribe EC. DATA
      SOURCES: Four hundred and sixty-seven NP students completed a 30-item web-based
      survey using Vovici survey software. CONCLUSIONS: Students who reported formal
      content on EC in their program of study showed significantly better mean
      knowledge scores (t= 5.279, df = 459, p < .001). Gaps in NP students' knowledge
      of EC mechanisms of action, understanding of indications and contraindications
      were apparent. Younger students (F(3,457) = 4.994, p < .002), those newer to
      nursing (F(4,456) = 6.641, p < .0005), and women's health NP students (F(4,445) =
      3.488, p < .008), demonstrated significantly better knowledge. Attitudes
      regarding EC appeared to be tied to the respondent's knowledge about EC.
      IMPLICATIONS FOR PRACTICE: Knowledge is an important factor in informing NP
      practice decisions. Clinicians need accurate, evidence-based knowledge to provide
      health education and counseling to reproductive age women if unintended
      pregnancies are to be reduced.

PMID- 23006020
TI  - Use and success of pharmacologic and nonpharmacologic strategies for sleep
      problems.
AB  - PURPOSE: The purpose of this web-based, quantitative, descriptive, correlational
      study was to identify frequency of use and success of strategies to alleviate
      sleep problems, to determine whether there is any relationship between use and
      success (perceived effectiveness) of strategies, on the one hand, and adults'
      gender, age, income, or education, on the other. DATA SOURCES: Data were
      collected from a web-based survey that examined strategy use and success to
      alleviate insomnia. CONCLUSIONS: The most frequently used strategies and those
      perceived as successful in alleviating sleep problems included medications and
      sleep hygiene strategies. Users of some strategies differed from nonusers on
      gender, age, income, and education. IMPLICATIONS FOR PRACTICE: Results from this
      study can be used to advise patients with sleep problems about choosing
      strategies to help alleviate those problems to reduce insomnia and to lower the
      risks of comorbid illness and healthcare costs. This study contributes to the
      current available findings that focus on determining which strategies are being
      used to alleviate sleep problems, those perceived as the most successful, and
      identifying strategy use and success based on demographics.

PMID- 23006021
TI  - Asymptomatic groin dermatophyte carriage detected during routine gynaecologic
      examinations.
AB  - We investigated the epidemiological characteristics of both symptomatic and
      asymptomatic dermatophytic groin infections in 1970 women (age: 36.2 +/- 12.5)
      during routine gynaecologic examinations. Bilateral groin samples were collected
      with sterile cotton swabs premoistened with sterile physiological saline. The
      samples were then separately inoculated onto Sabouraud glucose agar. Fungi were
      identified by sequencing the rDNA internal transcribed spacer region.
      Dermatophytes were recovered from five patients (four Trichophyton rubrum and one
      Arthroderma vanbreuseghemii, 0.25%) with a diagnosis of asymptomatic carriers
      (four) and tinea inguinalis (one). In one case, groin carriage converted into
      tinea inguinalis after 3 weeks. Analysis of risk factors indicated that patients
      of at least 49 years were more likely to be positive for dermatophyte isolation
      (P = 0.002). In conclusion, groin dermatophyte carriage is more common than tinea
      inguinalis and can potentially convert into a symptomatic infection.

PMID- 23006022
TI  - Ethnic disparities in the risk of adverse neonatal outcome after spontaneous
      preterm birth.
AB  - OBJECTIVE: To describe ethnic disparities in the risk of spontaneous preterm
      birth and related adverse neonatal outcome. DESIGN: Nationwide prospective cohort
      study. SETTING: The Netherlands, 1999-2007. POPULATION: Nine hundred and sixty
      nine thousand, four hundred and ninety-one singleton pregnancies with a
      spontaneous onset of labor. METHODS: We investigated ethnic disparities in
      perinatal outcome for European white, African, South-Asian, Mediterranean and
      East-Asian women. We performed multivariate logistic regression analyses to
      calculate the adjusted odds ratio (aOR) and confidence intervals (CIs) of
      spontaneous preterm birth and the risk of subsequent neonatal morbidity and
      mortality. MAIN OUTCOME MEASURES: The primary outcome measure was spontaneous
      preterm birth before 37 completed weeks of gestation. Secondarily, we
      investigated subsequent adverse neonatal outcome, which was a composite outcome
      of intraventricular hemorrhage, bronchopulmonary dysplasia, infant respiratory
      distress syndrome, neonatal sepsis or neonatal mortality within 28 days after
      birth. RESULTS: Compared with European whites, the aOR of delivering preterm was
      1.33 (95% CI 1.26-1.41) for African women, 1.58 (95% CI 1.47-1.69) for South
      Asians, 0.88 (95% CI 0.84-0.91) for Mediterraneans and 1.04 (95% CI 0.98-1.11)
      for East-Asians. Subsequent odds of adverse neonatal outcome were significantly
      lower for African (aOR 0.51; 95% CI 0.41-0.64) and Mediterranean women (aOR 0.86;
      95% CI 0.75-0.99) when compared with European whites. CONCLUSIONS: African and
      South-Asian women are at higher risk for preterm birth than European white women.
      However, the harmful effect of preterm birth on neonatal outcome is less severe
      for these women.

PMID- 23006023
TI  - Overnight heart rate variability in patients with obstructive sleep apnoea: a
      time and frequency domain study.
AB  - Heightened sympathetic activity plays a role in the cardiovascular sequelae of
      obstructive sleep apnoea (OSA). Cardiac autonomic function may be assessed non
      invasively by studying heart rate variability (HRV). The aim of the present study
      was to compare overnight HRV between a control group and a group of subjects with
      severe OSA. The potential confounding effects of age, sex, baseline autonomic
      status and sleep stage distribution were taken into account. Our prospective
      Holter study compared overnight (0030-0530 hours) HRV in 23 controls (apnoea
      hypopnoea index (AHI) = 5 +/- 3 /h) and 23 subjects with severe OSA (AHI = 65 +/-
      23 /h), matched for age and sex and with a similar percentage of rapid eye
      movement sleep. The mean normal-to-normal RR interval (NN) was shorter in the OSA
      compared with control group (903 vs 1039 ms, respectively), whereas the other
      time-domain indices of HRV, as well as the classic frequency-domain indices, were
      similar. Essentially similar results were obtained hourly and when only subjects
      with high mean values of the standard deviation of all NN (>= 90 ms) were
      evaluated. In the 0.01-0.06 Hz range corresponding to the typical OSA pattern of
      bradycardia-tachycardia termed cyclic variation of heart rate (CVHR), higher
      power was documented hourly in OSA, with a significant correlation between
      overnight power and both AHI and mean oxyhaemoglobin saturation. The percentage
      of NN > x ms different from the previous one (pNNx family) had no diagnostic
      value. The results of the present study suggest that NN may be the best index to
      quantify the overnight sympathovagal balance in OSA and that a spectral band
      overlapping the apnoea-related pattern of CVHR slightly improved the
      characterization of the apnoea-related HRV patterns.

PMID- 23006024
TI  - Anticoagulant use, the prevalence of bridging, and relation to length of stay
      among hospitalized patients with non-valvular atrial fibrillation.
AB  - OBJECTIVE: The objectives of this study were to describe inpatient
      anticoagulation and bridging in patients with non-valvular atrial fibrillation
      (NVAF) and to identify whether differences exist in length of stay (LOS) among
      bridged versus non-bridged NVAF patients. DESIGN: Administrative claims data were
      used to select patients >=18 years with a primary or secondary discharge
      diagnosis of NVAF and inpatient warfarin use from 1 July 2004 to 30 September
      2009. Patients with valvular or transient causes of NVAF or pregnancy were
      excluded. Inpatient bridging was defined as receipt of an anticoagulant in
      addition to warfarin during the hospitalization. LOS was reported for non-bridged
      patients (warfarin only) and compared with three bridging regimens: low molecular
      weight heparin/pentasaccharide (LMWH/PS); unfractionated heparin (UFH); and two
      agent bridging (LMWH/PS and UFH). Multivariate analyses were performed to
      evaluate the association between bridging and LOS, adjusting for demographic and
      clinical variables. RESULTS: Of 6340 NVAF patients, 48% received inpatient
      warfarin (mean LOS 5.5 days); among them, 64% received bridging therapy (mean LOS
      6.3 days) [LMWH/PS 45% (mean LOS 5.6 days), UFH 36% (mean LOS 6.0 days), two
      agent bridging 18% (mean LOS 8.4 days)]. Following multivariate analysis,
      relative to patients who received inpatient warfarin only, LOS was significantly
      higher for patients with UFH (19.3%) and patients with two-agent bridging
      (45.1%). Patients with pre-period warfarin, cancer, or diabetes mellitus who
      received bridging agents had significantly longer LOS than patients with those
      conditions who were not bridged. CONCLUSION: LOS was longer for bridged than non
      bridged patients. Further studies are needed to identify predictors of bridging
      and to explain why bridged NVAF patients had longer LOS.

PMID- 23006025
TI  - Tolerance to solar ultraviolet-B radiation in the citrus red mite, an upper
      surface user of host plant leaves.
AB  - Plant-dwelling mites are potentially exposed to solar ultraviolet-B (UVB)
      radiation that causes deleterious and often lethal effects, leading most mites to
      inhabit the lower (underside) leaf surfaces. However, in species of spider mite
      belonging to the Genus Panonychus, a substantial portion of individuals occur on
      upper leaf surfaces. We investigated whether the upper leaf surfaces of citrus
      trees are favorable for P. citri, and to what extent they are tolerant to UVB
      radiation. If eggs are not adequately protected from UVB damage, females may
      avoid ovipositing on the upper surfaces of sunny leaves. To test this, we
      conducted laboratory experiments using a UVB lamp, and semioutdoor manipulative
      experiments. As a result, P. citri eggs are tolerant to UVB. Field studies
      revealed that the ratio of eggs and adult females on upper leaf surfaces were
      larger for shaded than for sunny leaves. However, 64-89% of eggs hatched
      successfully even on sunny upper leaf surfaces. Nutritional evaluation revealed
      that whether on sunny or shaded leaves, in fecundity and juvenile development P.
      citri reaped the fitness benefits of upper leaf surfaces. Consequently, P. citri
      is tolerant to UVB damage, and inhabiting the upper surfaces of shaded leaves is
      advantageous to this mite.

PMID- 23006027
TI  - Psychodynamic psychiatry and psychoanalysis.

PMID- 23006028
TI  - Disorder in the domain of the personality disorders.
AB  - In contrast to medical conditions like cancer, pneumonia, and nephritis--all
      unequivocally diseases, application of the medical model to the domain of
      personality disorders is necessarily controversial. Everyone has a personality.
      The dividing lines between peculiarities and quirks, occasional outbursts under
      stress, persistent abnormalities of a mild sort, and chronic disorders with
      severe consequences for self and others--cannot readily be drawn, certainly not
      to universal agreement. Even where there is widespread acceptance about criteria
      for a particular disorder, one cannot speak prescriptively about its "ideal"
      treatment. The current diagnostic manual in psychiatry (DSM-IV) will soon be
      replaced by DSM-V. Some of the deficiencies and ambiguities of the last edition
      will be corrected; new ones will appear. There will always be some disagreement,
      in effect--some "disorder" in the domain of personality disorders. In this
      article some of the more pervasive problem areas are outlined. Among them: the
      continuum between personality oddity, outright personality disorder, and the more
      disease-like symptom-disorder pertinent to almost all the currently recognized
      Axis II disorders. Also: the effects of culture on what is-or is not-recognized
      as a valid disorder of personality, the inherent complexities in the personality
      domain (which require attention to dimensional as well as category-based
      concepts), the overlap among the various categories, the tendency (especially in
      forensic work) toward diagnostic oversimplification (as though all narcissists or
      borderlines are alike), the interactions of genetic, prenatal, and environmental
      factors, and lastly, the importance of traits-including the often neglected
      positive traits modifying any given disorder. Awareness of these factors can help
      reduce, though not eliminate, the disorder in the personality disorder domain.

PMID- 23006029
TI  - Moving beyond specialized therapies for borderline personality disorder: the
      importance of integrated domain-focused treatment.
AB  - This article argues the recent emphasis on specializing treatments for borderline
      personality disorder needs to be replaced by a more integrated and evidence-based
      approach that combines effective methods from all therapies. This proposition is
      based on evidence that specialized treatments for borderline personality disorder
      do not differ significantly from each and that they are not more effective than
      good structured care designed to meet the needs of patients with the disorder. It
      is also argued that current therapies are limited because they do not recognize
      or accommodate the extensive heterogeneity of borderline personality disorder and
      its complex etiology. These factors make a one-approach-fits-all strategy
      inappropriate for treatment. An integrated approach is proposed as an alternative
      to the specialized therapies that makes use of all effective interventions
      regardless of their conceptual origins and delivers them in a coordinated way. A
      two-component framework is proposed for organizing integrated treatment: 1. a
      system for conceptualizing borderline personality disorder based on current
      empirical knowledge about the structure, etiology, and stability of borderline
      pathology that serves as a guide when selecting and delivering interventions; and
      2. a model of therapeutic change based on the general literature on psychotherapy
      outcome and specific studies of PD treatments. This framework proposes that
      integrated treatment be organized around principles of therapeutic change common
      to all effective therapies supplemented with more specific treatment methods
      taken from the different therapies as needed to tailor treatment to individual
      patients and treat specific problems and psychopathology.

PMID- 23005937
TI  - Search for a light pseudoscalar Higgs boson in the dimuon decay channel in pp
      collisions at ?s = 7 TeV.
AB  - The dimuon invariant mass spectrum is searched in the range between 5.5 and 14
      GeV for a light pseudoscalar Higgs boson a, predicted in a number of new physics
      models, including the next-to-minimal supersymmetric standard model. The data
      sample used in the search corresponds to an integrated luminosity of 1.3 fb(-1)
      collected in pp collisions at ?s = 7 TeV with the CMS detector at the LHC. No
      excess is observed above the background predictions and upper limits are set on
      the cross section times branching fraction sigma * B(pp->a->MU(+)MU(-)) in the
      range of 1.5-7.5 pb. These results improve on existing bounds on the abb coupling
      for m(a) < m(Upsilon(1S)) and are the first significant limits for m(a) >
      m(Upsilon(3S)). Constraints on the supersymmetric parameter space are presented
      in the context of the next-to-minimal model.

PMID- 23006030
TI  - Overwhelming patients and overwhelmed therapists.

PMID- 23006031
TI  - Neurocognitive deficits in borderline personality disorder: implications for
      treatment.
AB  - The cognitive dimension of Borderline Personality Disorder has received
      relatively little attention in the clinical literature and is poorly understood.
      This article illustrates how a range of cognitive problems including attention
      deficit disorder and learning disabilities may contribute to the cognitive
      disturbances identified in the disorder including dissociation, paranoia, all or
      nothing thinking, overvalued ideas, and denial and splitting. A review of
      relevant research supporting the presence of cognitive deficits is summarized
      along with a developmental pathway for the expression of the cognitive dimension.
      Clinical examples are provided. Recommendations for inclusion of assessment and
      treatment strategies that address cognitive deficits within a psychodynamically
      based psychotherapy are discussed.

PMID- 23006032
TI  - Childhood precursors of personality disorders: evaluation and treatment.

PMID- 23006034
TI  - Air quality, mortality, and economic benefits of a smoke - free workplace law for
      non-smoking Ontario bar workers.
AB  - We estimated the impact of a smoke-free workplace bylaw on non-smoking bar
      workers' health in Ontario, Canada. We measured bar workers' urine cotinine
      before (n = 99) and after (n = 91) a 2004 smoke-free workplace bylaw. Using
      pharmacokinetic and epidemiological models, we estimated workers' fine-particle
      (PM2.5 ) air pollution exposure and mortality risks from workplace secondhand
      smoke (SHS). workers' pre-law geometric mean cotinine was 10.3 ng/ml; post-law
      dose declined 70% to 3.10 ng/ml and reported work hours of exposure by 90%. Pre
      law, 97% of workers' doses exceeded the 90th percentile for Canadians of working
      age. Pre-law-estimated 8-h average workplace PM2.5 exposure from SHS was 419
      MUg/m(3) or 'Very Poor' air quality, while outdoor PM2.5 levels averaged 7
      MUg/m(3) , 'Very Good' air quality by Canadian Air Quality Standards. We
      estimated that the bar workers' annual mortality rate from workplace SHS exposure
      was 102 deaths per 100000 persons. This was 2.4 times the occupational disease
      fatality rate for all Ontario workers. We estimated that half to two-thirds of
      the 10620 Ontario bar workers were non-smokers. Accordingly, Ontario's smoke-free
      law saved an estimated 5-7 non-smoking bar workers' lives annually, valued at CA
      $50 million to $68 million (US $49 million to $66 million).

PMID- 23006035
TI  - Ergonomics and sustainability: towards an embrace of complexity and emergence.
AB  - Technology offers a promising route to a sustainable future, and ergonomics can
      serve a vital role. The argument of this article is that the lasting success of
      sustainability initiatives in ergonomics hinges on an examination of ergonomics'
      own epistemology and ethics. The epistemology of ergonomics is fundamentally
      empiricist and positivist. This places practical constraints on its ability to
      address important issues such as sustainability, emergence and complexity. The
      implicit ethical position of ergonomics is one of neutrality, and its positivist
      epistemology generally puts value-laden questions outside the parameters of what
      it sees as scientific practice. We argue, by contrast, that a discipline that
      deals with both technology and human beings cannot avoid engaging with questions
      of complexity and emergence and seeking innovative ways of addressing these
      issues. PRACTITIONER SUMMARY: Ergonomics has largely modelled its research on a
      reductive science, studying parts and problems to fix. In sustainability efforts,
      this can lead to mere local adaptations with a negative effect on global
      sustainability. Ergonomics must consider quality of life globally, appreciating
      complexity and emergent effects of local relationships.

PMID- 23006033
TI  - Modeling borderline personality disorder based on the neurobehavioral foundation
      of major personality traits.
AB  - Borderline personality disorder (BPD) is an exceedingly complex behavioral
      phenomenon that is in need of conceptual clarification within a larger model of
      personality disorders (PDs). The association of personality traits to BPD is
      discussed initially as a means of introducing a dimensional personality approach
      to understanding BPD. While this model suggests that PDs emerge at the extremes
      of personality dimensions, attempts to demonstrate such an association have been
      empirically disappointing and conceptually unilluminating. Therefore, in this
      article, we attempt to extend such models by outlining the neurobehavioral
      systems that underlie major personality traits, and highlight the evidence that
      they are subject to experience-dependent modification that can be enduring
      through effects on genetic expression, mainly through processes known as
      epigenetics. It is through such processes that risk for personality disorder may
      be modified by experience at any point in development, but perhaps especially
      during early critical periods of development. We conclude by presenting a
      multidimensional model of PDs, in general, and BPD, in particular, that relies on
      the concepts developed earlier in the article. Our goal is to provide a guide for
      novel clinical conceptualization and assessment of PDs, as well as research on
      their psychobiological nature and pharmacological treatment.

PMID- 23006036
TI  - The experience of being a female carrier of haemophilia and the mother of a
      haemophilic child.
AB  - Limited research has been conducted on how the female carrier experiences her
      life with a haemophilic child, and earlier studies are mostly questionnaire
      based. No previous qualitative study on the female carrier's situation has been
      conducted in Sweden. The aim of the study was to describe the lived experience of
      being a carrier of severe or moderate haemophilia and of being the mother of a
      haemophilic child. The study was conducted via qualitative interviews and
      analysed by means of a phenomenological hermeneutic method; a total of 13
      haemophilia carriers were interviewed in 2010. Being a carrier of haemophilia and
      having a haemophilic child was life changing. The women moved from a state of
      sad, guilty chaos to reconciling themselves with the new situation. Our analysis
      revealed three acts in which phenomena appeared: the time after diagnosis, the
      turning point and reconciliation with a changing life. Emerging as crucial to the
      process of reconciliation with a changing life was a sense of being fully
      informed and supported. The Haemophilia Treatment Centre (HTC) should create an
      environment that encourages learning, and the team should invite and encourage
      the woman's partner to be actively involved in the child's care. Moreover, the
      results indicate that it would be beneficial to invite female carriers to receive
      patient education at the HTC before they plan to start a family. During this
      visit, the woman may gain a greater understanding of her carriership to prepare
      her for future decisions concerning prenatal diagnosis, for example.

PMID- 23006037
TI  - Exercise identity as a risk factor for exercise dependence.
AB  - OBJECTIVES: The aim of the study was to explore the relationship between exercise
      identity and exercise dependence. We hypothesized that stronger exercise
      identities would be associated with greater odds of experiencing exercise
      dependence symptoms. DESIGN: Logistic regression was used to assess the extent of
      association between exercise identity and the risk of experiencing exercise
      dependence symptoms. METHOD: Participants (101) were recruited online via sports
      clubs and social networking sites and were asked to complete online measures of
      exercise identity and exercise dependence. RESULTS: The overall model fit was a
      significant improvement on the baseline model, but only the exercise beliefs
      factor was significantly associated with the odds of dependence symptoms, with
      higher scores on the belief scale predicting greater odds of experiencing
      dependence symptoms. Exercise role identity, in contrast, was not significantly
      associated with odds of experiencing dependence symptoms. Per cent correct
      classification was 55.9% for asymptomatic and 88.2% for symptomatic individuals
      and the overall per cent correct classification was 77.5%. CONCLUSIONS: The
      relation between identity and dependence could represent both a fruitful research
      avenue and a potential therapeutic target for those experiencing dependence
      symptoms; although our findings only showed a relationship between one of the two
      factors of the exercise identity measure and dependence. Longitudinal research is
      required to examine the relationship between identity and dependence in the
      context of other variables to better understand why some individuals become
      exercise dependent whereas others do not. STATEMENT OF CONTRIBUTION: What is
      already known on this subject? Exercise identity has been identified as an
      important determinant of exercise behaviour and studies within the exercise
      identity framework have proven elucidative with respect to the psychological
      processes that may underpin commitment to exercise. It has separately been
      established that some individuals may become dependent on exercise and exhibit
      symptoms indicative of a behavioural addiction to exercise according in line with
      clinical definitions. What does this study add? Psychological explanation for
      exercise dependence based on escalation of normal exercise identity processes.
      Empirical investigation of identity-dependence link using a sample of physically
      active individuals. Comparison of two alternative structures for the exercise
      identity construct.

PMID- 23006038
TI  - Electrogram mapping to facilitate pulmonary vein isolation in the era of wide
      area antral ablation.

PMID- 23006039
TI  - The effect of restrictive bariatric surgery on urolithiasis.
AB  - BACKGROUND AND PURPOSE: Roux-en-Y gastric bypass (RYGB) surgery, a mixed
      malabsorptive/restrictive procedure, is associated with enteric hyperoxaluria and
      an increased risk of kidney stones. The incidence of nephrolithiasis after purely
      restrictive bariatric procedures such as adjustable gastric banding or sleeve
      gastrectomy has not been well described. We aim to analyze the incidence of
      kidney stones in patients who undergo either adjustable gastric banding or sleeve
      gastrectomy. PATIENTS AND METHODS: In a retrospective study, we analyzed a pool
      of 332 patients who underwent adjustable gastric banding and 85 patients who
      underwent sleeve gastrectomy at the University of California, San Diego Center
      for the Treatment for Obesity within a 54-month period (September 2006 to
      February 2011). The primary outcomes of urinary calculus diagnosis and surgical
      treatment were investigated using manual chart review and International
      Classification of Diseases and Related Health Problems-9 code electronic search.
      RESULTS: Within the adjustable gastric banding cohort, we found a person-time
      incidence rate of 3.40 stone diagnoses per 1000 person-years. Within the sleeve
      gastrectomy cohort, we found a person-time incidence rate of 5.25 stone diagnoses
      per 1000 person-years. CONCLUSIONS: Questions remain whether purely restrictive
      bariatric procedures such as sleeve gastrectomy or adjustable gastric banding
      avoid the risk of kidney stones. Our study demonstrates a very low incidence of
      kidney stones after restrictive bariatric procedures, although larger sample
      sizes, longer follow-up times, and controlled prospective studies are necessary
      to validate this finding.

PMID- 23006040
TI  - Longitudinal associations between executive control and developing mathematical
      competence in preschool boys and girls.
AB  - Executive control (EC) is related to mathematics performance in middle childhood.
      However, little is known regarding how EC and informal numeracy differentially
      support mathematics skill acquisition in preschoolers. A sample of preschoolers
      (115 girls, 113 boys), stratified by social risk, completed an EC task battery at
      3 years, informal numeracy assessments at 3.75 and 4.5 years, and a broad
      mathematics assessment during kindergarten. Strong associations were observed
      between latent EC at age 3 and mathematics achievement in kindergarten, which
      remained robust after accounting for earlier informal numeracy, socioeconomic
      status, language and processing speed. Relations between EC and mathematics
      achievement were stronger in girls than in boys. Findings highlight the unique
      role of EC in predicting which children may have difficulty transitioning to
      formal mathematics instruction.

PMID- 23006042
TI  - Highly enhanced affinity of multidentate versus bidentate zwitterionic ligands
      for long-term quantum dot bioimaging.
AB  - High colloidal stability in aqueous conditions is a prerequisite for fluorescent
      nanocrystals, otherwise known as "quantum dots", intended to be used in any long
      term bioimaging experiment. This essential property implies a strong affinity
      between the nanoparticles themselves and the ligands they are coated with. To
      further improve the properties of the bidentate monozwitterionic ligand
      previously developed in our team, we synthesized a multidentate polyzwitterionic
      ligand, issued from the copolymerization of a bidentate monomer and a
      monozwitterionic one. The nanocrystals passivated by this polymeric ligand showed
      an exceptional colloidal stability, regardless of the medium conditions (pH,
      salinity, dilution, and biological environment), and we demonstrated the affinity
      of the polymer exceeded by 3 orders of magnitude that of the bidentate ligand
      (desorption rates assessed by a competition experiment). The synthesis of the
      multidentate polyzwitterionic ligand proved also to be easily tunable and allowed
      facile functionalization of the corresponding quantum dots, which led to
      successful specific biomolecules targeting.

PMID- 23006041
TI  - Design, synthesis, and structure-activity relationships of highly potent 5-HT3
      receptor ligands.
AB  - The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an
      important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl
      2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3
      hit fragment. Here we describe the synthesis and structure-activity relationships
      (SAR) of a series of (iso)quinoline and quinazoline compounds that were
      synthesized and screened for 5-HT3 R affinity using a [3H]granisetron
      displacement assay. These studies resulted in the discovery of several high
      affinity ligands of which compound 22 showed the highest affinity (pK(i) > 10)
      for the 5-HT3 receptor. The observed SAR is in agreement with established
      pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding
      mode prediction using homology modeling and in silico docking approaches.

PMID- 23006043
TI  - Losartan alleviates renal fibrosis by down-regulating HIF-1alpha and up
      regulating MMP-9/TIMP-1 in rats with 5/6 nephrectomy.
AB  - BACKGROUND: This study investigated the effects of losartan intervention on the
      expressions of hypoxia-inducible factor-1alpha (HIF-1alpha), matrix
      metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      in renal fibrosis in rats with 5/6 nephrectomy. METHODS: Sprague Dawley rats were
      randomly divided into three groups. Rats in the losartan group were gavaged with
      losartan (33.3 mg/kg/day) from 1 week after 5/6 nephrectomy, and those in the
      sham group and the model group only received an equal volume of saline solution
      by gavage. Rats were sacrificed at the ends of the 4, 8 and 12 weeks,
      respectively. Urinary N-acetyl-glucosaminidase (NAG), 24-h urinary protein, serum
      cystatin C, blood urea nitrogen (BUN), and serum creatinine (Scr) levels were
      assessed. Kidney tissues were observed under light and electron microscope. The
      expressions of HIF-1alpha, transforming growth factor-beta1 (TGF-beta1), MMP-9,
      and TIMP-1 were determined by immunohistochemistry and Western blotting. RESULTS:
      Twenty-four hour urinary protein, urinary NAG, serum cystatin C, BUN, and Scr
      levels in the model group were significantly higher than those in the sham group
      (p < 0.05), but losartan treatment improved these changes. The apparent
      glomerular sclerosis and tubulointerstitial fibrosis were also found in the model
      group, which were ameliorated by losartan. The expressions of HIF-1alpha, TGF
      beta1, MMP-9, and TIMP-1 were elevated and MMp-9/TIMP-1 ratio was lowered in the
      model group (p < 0.05), but losartan increased the expression of MMP-9 and MMp
      9/TIMP-1 ratio (p < 0.05) and lessened the expressions of HIF-1alpha, TGF-beta1,
      and TIMP-1 (p < 0.05). CONCLUSION: Losartan may ameliorate renal fibrosis partly
      by down-regulating HIF-1alpha and up-regulating MMP-9/TIMP-1 in rats with 5/6
      nephrectomy.

PMID- 23006044
TI  - Low-voltage organic field effect transistors with a 2-tridecyl[1]benzothieno[3,2
      b][1]benzothiophene semiconductor layer.
AB  - An asymmetric n-alkyl substitution pattern was realized in 2
      tridecyl[1]benzothieno[3,2-b][1]benzothiophene (C(13)-BTBT) in order to improve
      the charge transport properties in organic thin-film transistors. We obtained
      large hole mobilities up to 17.2 cm(2)/(V.s) in low-voltage operating devices.
      The large mobility is related to densely packed layers of the BTBT pi-systems at
      the channel interface dedicated to the substitution motif and confirmed by X-ray
      reflectivity measurements. The devices exhibit promising stability in continuous
      operation for several hours in ambient air.

PMID- 23006045
TI  - A positive event dependence model for self-controlled case series with
      applications in postmarketing surveillance.
AB  - A primary objective in the application of postmarketing drug safety surveillance
      is to ascertain the relationship between time-varying drug exposures and
      recurrent adverse events (AEs) related to health outcomes. The self-controlled
      case series (SCCS) method is one approach to analysis in this context. It is
      based on a conditional Poisson regression model, which assumes that events at
      different time points are conditionally independent given the covariate process.
      This requirement is problematic when the occurrence of an event can alter the
      future event risk. In a clinical setting, for example, patients who have a first
      myocardial infarction (MI) may be at higher subsequent risk for a second. In this
      work, we propose the positive dependence self-controlled case series (PD-SCCS)
      method: a generalization of SCCS that allows the occurrence of an event to
      increase the future event risk, yet maintains the advantages of the original
      model by controlling for fixed baseline covariates and relying solely on data
      from cases. As in the SCCS model, individual-level baseline parameters drop out
      of the PD-SCCS likelihood. Data sources used for postmarketing surveillance can
      contain tens of millions of people, so in this situation it is particularly
      advantageous that PD-SCCS avoids doing a costly estimation of individual
      parameters. We develop expressions for large sample inference and optimization
      for PD-SCCS and compare the results of our generalized model with the more
      restrictive SCCS approach.

PMID- 23006047
TI  - Epigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian
      cancer progression.
AB  - AIM: The BRCA1 promoter is hypermethylated in ovarian cancer patients. We
      postulated that this hypermethylation might be involved in ovarian cancer
      progression. METHODS: To confirm our hypothesis, tissue and serum samples were
      collected from ovarian carcinoma patients and categorized according to tumor
      stage. Healthy or benign ovarian disease tissue samples and corresponding serum
      samples were used as controls. Breast and ovarian cancer susceptibility gene 1
      (BRCA1) promoter methylation levels were detected by real-time polymerase chain
      reaction (PCR). Real-time PCR was also used to evaluate BRCA1 gene expression,
      and Western blot was performed to assay the expression of BRCA1 protein. RESULTS:
      BRCA1 showed hypomethylation in 30 normal ovarian and 30 benign ovarian tumors,
      but showed hypermethylation or methylation in ovarian cancer patients. There was
      also a significant difference in the BRCA1 promoter methylation levels between
      different ovarian cancer stages. Compared to stage I and the control groups,
      there were higher BRCA1 promoter methylation frequencies in stage II and III
      ovarian cancers. BRCA1 methylation correlated with the loss of BRCA1 expression.
      BRCA1 promoter in stage I tumors showed hypomethylated. CONCLUSION: Promoter
      hypermethylation may act as a biomarker for sporadic ovarian cancer progression,
      but is unlikely to be helpful in the early diagnosis of ovarian cancer.

PMID- 23006048
TI  - HIV-1 imposes rigidity on blood and semen cytokine networks.
AB  - PROBLEM: Although it is established that the levels of individual cytokines are
      altered by HIV-1 infection, the changes in cytokine interrelations that organize
      them into networks have been poorly studied. Here, we evaluated these networks in
      HIV-infected and HIV-uninfected individuals in fluid compartments that are
      critical for HIV-1 pathogenesis and transmission, namely blood and semen. METHOD
      OF STUDY: In samples collected from therapy-naive HIV-1-infected and HIV-1
      uninfected individuals, we measured HIV-1-load, CD4 cell count, and levels of 21
      cytokines using a multiplex bead assay. RESULTS: Cytokine networks in blood and
      semen were different for HIV-1-infected and HIV-1-uninfected individuals. In both
      compartments of HIV-1-infected individuals, the cytokine networks were more
      interlocked than in controls: HIV-1 infection resulted in the establishment of
      new correlations and in the strengthening of pre-existing correlations between
      different cytokines. In blood and semen of HIV-infected patients, there were,
      respectively, 68 and 72 statistically significant correlations between cytokines,
      while in uninfected individuals, there were 18 and 21 such correlations.
      CONCLUSION: HIV-1 infection reorganizes the cytokine networks, establishing new
      strong correlations between various cytokines and thus imposes a high rigidity on
      the cytokine network. This rigidity may reflect the impairment of the ability of
      the immune system to respond to microbial challenges.

PMID- 23006049
TI  - Polyphosphate binds to human von Willebrand factor in vivo and modulates its
      interaction with glycoprotein Ib.
AB  - BACKGROUND: Polyphosphate, a phosphate polymer released by activated platelets,
      has recently been described as a potent modulator of blood coagulation and
      fibrinolysis. In blood plasma, polyphosphate binds to and alters the biological
      functions of factor XII, fibrin(ogen), thrombin and factor VII activating
      protease. OBJECTIVES: The aim of the present study is to investigate whether
      polyphosphate also binds to von Willebrand factor (VWF) and alters some of its
      activities. METHODS/RESULTS: When studying patients with type 1 von Willebrand
      disease (VWD) and their healthy relatives, we discovered a significant
      correlation between von Willebrand factor (VWF) and platelet polyphosphate
      levels. We have also found polyphosphate in preparations of VWF isolated from
      normal platelets and plasma. Surface plasmon resonance and electrophoretic
      mobility assays indicated that polyphosphate interacts with VWF in a dose- and
      time-dependent manner. Treatment of normal plasma with active exopolyphosphatase
      decreased the VWF ristocetin cofactor (VWF:RCo) activity, a functional measure of
      VWF binding to platelet glycoprotein receptor Ib. VWF collagen binding and
      multimerization were unaltered after polyphosphate depletion. Moreover, addition
      of polyphosphate increased the deficient VWF:RCo activity presented by plasma
      from patients with type 1 VWD. CONCLUSIONS: Our results reveal that a new role is
      played by polyphosphate in hemostasis by its interaction with VWF, and suggest
      that this polymer may be effective in the treatment of some types of VWD.

PMID- 23006050
TI  - Intimate partner violence and HIV risk factors among African-American and African
      Caribbean women in clinic-based settings.
AB  - Despite progress against intimate partner violence (IPV) and HIV/AIDS in the past
      two decades, both epidemics remain major public health problems, particularly
      among women of color. The objective of this study was to assess the relationship
      between recent IPV and HIV risk factors (sexual and drug risk behaviors, sexually
      transmitted infections [STIs], condom use, and negotiation) among women of
      African descent. We conducted a comparative case-control study in women's health
      clinics in Baltimore, MD, USA and St. Thomas and St. Croix, US Virgin Islands
      (USVI). Women aged 18-55 years who experienced physical and/or sexual IPV in the
      past two years (Baltimore, n=107; USVI, n=235) were compared to women who never
      experienced any form of abuse (Baltimore, n=207; USVI, n=119). Logistic
      regression identified correlates of recent IPV by site. In both sites, having a
      partner with concurrent sex partners was independently associated with a history
      of recent IPV (Baltimore, AOR: 3.91, 95% CI: 1.79-8.55 and USVI, AOR: 2.25, 95%
      CI: 1.11-4.56). In Baltimore, factors independently associated with recent IPV
      were lifetime casual sex partners (AOR: 1.99, 95% CI: 1.11-3.57), exchange sex
      partners (AOR: 5.26, 95% CI: 1.92-14.42), infrequent condom use during vaginal
      sex (AOR: 0.24, 95% CI: 0.08-0.72), and infrequent condom use during anal sex
      (AOR: 0.29, 95% CI: 0.09-0.93). In contrast, in the USVI, having a concurrent sex
      partner (AOR: 3.33, 95% CI: 1.46-7.60), frequent condom use during vaginal sex
      (AOR: 1.97, 95% CI: 1.06-3.65), frequent condom use during anal sex (AOR: 6.29,
      95% CI: 1.57-25.23), drug use (AOR: 3.16, 95% CI: 1.00-10.06), and a past-year
      STI (AOR: 2.68, 95% CI: 1.25-5.72) were associated with recent IPV history. The
      divergent results by site warrant further investigation into the potential
      influence of culture, norms, and intentions on the relationships examined.
      Nonetheless, study findings support a critical need to continue the development
      and implementation of culturally tailored screening for IPV within HIV prevention
      and treatment programs.

PMID- 23006052
TI  - Nonylphenol polyethoxylates degraded by three different wavelengths of UV and
      their genotoxic change--detected by generation of gamma-H2AX.
AB  - UV rays in sunlight are an important factor in the degradation of chemicals. In
      this study, we investigated the degradation of nonionic surfactants, nonylphenol
      polyethoxylates (NPEOs) with 10 or 70 ethylene oxide (EO) units using UVA, B and
      C, and their genotoxic change based on phosphorylation of histone H2AX (gamma
      H2AX), a marker of DNA damage. NPEOs were degraded dependent on the energy of UV,
      that is, UVC having the highest energy was most effective, whereas UVA having the
      lowest energy caused little change. The EO side chain of NPEO(70) was broken near
      the benzene ring by UV, producing NPEOs with a shortened EO chain (around 10
      units). The generation of gamma-H2AX reflected the pattern of degradation;
      shortening of the EO chain changed NPEO(70) into an inducer for gamma-H2AX, and
      degradation of NPEO(10) attenuated the genotoxicity. The gamma-H2AX generated by
      NPEO(10) and UV-degraded NPEO(70) was independent of the cell cycle. The
      formation of DNA double strand breaks detected by gel electrophoresis was
      consistent with the results for gamma-H2AX. These results suggested that UV rays
      can make NPEOs harmless or genotoxic according to the degradation of the EO side
      chain, the effects being dependent on wavelength.

PMID- 23006051
TI  - The attenuation of early benzo(a)pyrene-induced carcinogenic insults by diallyl
      disulfide (DADS) in MCF-10A cells.
AB  - Diallyl disulfide (DADS), a garlic organosulfur compound, has been researched as
      a cancer prevention agent; however, the role of DADS in the suppression of cancer
      initiation in nonneoplastic cells has not been elucidated. To evaluate DADS
      inhibition of early carcinogenic events, MCF-10A cells were pretreated (PreTx)
      with DADS followed by the ubiquitous carcinogen benzo(a)pyrene (BaP), or
      cotreated (CoTx) with DADS and BaP for up to 24 h. The cells were evaluated for
      changes in cell viability/proliferation, cell cycle, induction of peroxide
      formation, and DNA damage. BaP induced a statistically significant increase in
      cell proliferation at 6 h, which was attenuated with DADS CoTx. PreTx with 6 and
      60 MUM of DADS inhibited BaP-induced G2/M arrest by 68% and 78%, respectively.
      DADS, regardless of concentration or method, inhibited BaP-induced extracellular
      aqueous peroxide formation within 24 h. DADS attenuated BaP-induced DNA single
      strand breaks at all time points through both DADS Pre- and CoTx, with
      significant inhibition for all treatments sustained after 6 h. DADS was effective
      in inhibiting BaP-induced cell proliferation, cell cycle transitions, reactive
      oxygen species, and DNA damage in a normal cell line, and thus may inhibit
      environmentally induced breast cancer initiation.

PMID- 23006053
TI  - Evidence for radical-mediated catalysis by HppE: a study using cyclopropyl and
      methylenecyclopropyl substrate analogues.
AB  - (S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear
      iron enzyme that catalyzes the oxidative epoxidation of (S)-2
      hydroxypropylphosphonic acid ((S)-HPP) in the biosynthesis of the antibiotic
      fosfomycin. HppE also recognizes (R)-2-hydroxypropylphosphonic acid ((R)-HPP) as
      a substrate and converts it to 2-oxo-propylphosphonic acid. To probe the
      mechanisms of these HppE-catalyzed oxidations, cyclopropyl- and
      methylenecyclopropyl-containing compounds were synthesized and studied as radical
      clock substrate analogues. Enzymatic assays indicated that the (S)- and (R)
      isomers of the cyclopropyl-containing analogues were efficiently converted to
      epoxide and ketone products by HppE, respectively. In contrast, the ultrafast
      methylenecyclopropyl-containing probe inactivated HppE, consistent with a rapid
      radical-triggered ring-opening process that leads to enzyme inactivation. Taken
      together, these findings provide, for the first time, experimental evidence for
      the involvement of a C2-centered radical intermediate with a lifetime on the
      order of nanoseconds in the HppE-catalyzed oxidation of (R)-HPP.

PMID- 23006054
TI  - Use of a pressure guidewire to assess pulmonary artery band adequacy in the
      hybrid stage I procedure for high-risk neonates with hypoplastic left heart
      syndrome and variants.
AB  - OBJECTIVE: The hybrid stage I procedure is an alternative palliative strategy for
      patients with hypoplastic left heart syndrome who traditionally have undergone
      the Norwood operation. At our institution, the hybrid stage I procedure is
      employed only for patients with high operative risk. Our objective was to
      describe our use of a pressure guidewire during the hybrid stage I procedure to
      assess quantitatively pulmonary artery band adequacy. DESIGN: After reviewing the
      charts on all high-risk patients who underwent a hybrid stage I procedure at our
      institution, we compared two groups of patients: those who underwent the standard
      hybrid stage I palliation (standard cohort) and those with pressure wire
      facilitated assessment of distal branch pulmonary artery pressure (pressure wire
      cohort) to evaluate the impact of pressure guidewire use on procedural risk,
      radiation time, patient outcomes, and need for reoperation for pulmonary artery
      band adjustment. RESULTS: The pressure guidewire was used in 8 of 14 patients at
      the time of hybrid stage I procedure and was successful and without complication
      in all attempts. In the standard cohort, 67% of patients needed reoperation for
      pulmonary artery band adjustment, compared to 12.5% of patients in the pressure
      wire cohort (P =.09). Procedure time, radiation exposure, and survival to
      hospital discharge were not different between groups. CONCLUSIONS: This novel use
      of a pressure guidewire to assess quantitatively pulmonary artery band adequacy
      at the time of placement is feasible, safe and may decrease the need for
      reoperation for pulmonary artery band adjustment.

PMID- 23006055
TI  - Qualitative approaches to understanding patient preferences.
AB  - Achieving patient-centered care depends on a thorough understanding of patient
      preferences at all stages of their journeys through healthcare. Qualitative
      research methods provide the means to systematically collect and analyze these
      preferences. Qualitative approaches to research are diverse in character, but
      many such approaches have a long history and strong disciplinary roots. Despite
      variation, most qualitative approaches work inductively from the 'ground up', and
      seek to build knowledge and understanding rather than test hypotheses. Their use
      to explore patient pathways through care has offered insight into reasons why
      people become patients in the first instance, their preferences for treatment
      options and degree of involvement in decisions, and their preferences for
      healthcare delivery. Qualitative approaches are sometimes used alongside
      'quantitative' in mixed methods designs, requiring solid expertise and
      resourcing. Expertise is also crucial in the assessment of quality in qualitative
      research, and efforts to develop checklists to assess quality are challenged by
      evidence about the importance of expertise-based judgments. Recent developments
      in health research include an upsurge in patient involvement activities in design
      of research and healthcare services; these may seem similar to qualitative
      research, but are in fact very different. While an important part of the research
      landscape, patient involvement activities are not intended to provide robust
      research-based evidence about patients' preferences or experiences. There is
      pressing need to bridge the gap between qualitative research evidence and patient
      involvement in the design of research and services. Participatory research
      methods that harness qualitative approaches may be a way to achieve this.

PMID- 23006056
TI  - A further look into compensatory health beliefs: a think aloud study.
AB  - OBJECTIVES: Compensatory health beliefs are hypothesized to be a means by which
      people compensate for the negative effects of performing an unhealthy behaviour
      by engaging in a health-protective behaviour (Knauper, Rabiau, Cohen, & Patriciu,
      2004). However, the measurement of compensatory health beliefs has proven
      problematic (e.g., Radtke, Scholz, Keller, Perren, & Hornung, 2010) and so the
      aims of the present study are to identify: (a) the kinds of difficulties that
      people experience when completing compensatory health belief scales; and (b) what
      steps will be required to develop a future reliable and valid measure of
      compensatory health beliefs. DESIGN: Cross-sectional survey. METHODS: Forty-three
      participants (M = 34.98 years, SD = 13.94) completed the compensatory health
      beliefs questionnaire while thinking aloud. Participants' responses to the
      compensatory health beliefs scale were coded using French, Cooke, McLean,
      Williams, and Sutton's (2007) schedule. RESULTS: Consistent with prior research,
      the full compensatory health beliefs scale showed evidence of internal
      reliability, and face validity. Participants identified several conceptual
      ambiguities, most notably: (a) between belief- and behaviour-based compensation
      (i.e., participants did not believe in the compensatory health belief, but still
      engaged in the affiliated compensatory behaviour), and (b) the 'effectiveness' of
      the beliefs (i.e., participants talked about engaging in the compensatory
      behaviour, but acknowledged that it was only a partial solution). CONCLUSIONS:
      Although the compensatory health belief subscales lack reliability, the measure
      as a whole possesses face validity. Further work is required to refine the
      compensatory health beliefs scale by discriminating between compensatory health
      beliefs and compensatory health behaviours. STATEMENT OF CONTRIBUTION: What is
      already known on this subject? Although the idea that people use compensatory
      health beliefs as a strategy to continue engaging in unhealthy behaviours is an
      appealing one, attempts to measure compensatory health beliefs has produced mixed
      findings (see Kaklamanou & Armitage, ; Knauper et al., ; Nooijer, Puijk-Hekman, &
      Assema, ; Radtke et al., ). What does this study add? The present study, using a
      'think aloud technique', suggests ways to improve reliability of the compensatory
      health beliefs scale. We suggest that three sub-strategies underpin the 'activate
      Compensatory Health Beliefs' strategy. We propose a new construct that we call
      'compensatory health behaviours'.

PMID- 23006057
TI  - A step towards a faster and easier cryoballoon ablation.

PMID- 23006059
TI  - Investigating the cognitive precursors of emotional response to cancer stress: re
      testing Lazarus's transactional model.
AB  - OBJECTIVES: Lazarus's Transactional Model of stress and coping underwent
      significant theoretical development through the 1990s to better incorporate
      emotional reactions to stress with their appraisal components. Few studies have
      robustly explored the full model. This study aimed to do so within the context of
      a major life event: cancer diagnosis. DESIGN: A repeated measures design was used
      whereby data were collected using self-report questionnaire at baseline (soon
      after diagnosis), and 3- and 6-month follow-up. METHODS: A total of 160 recently
      diagnosed cancer patients were recruited (mean time since diagnosis = 46 days).
      Their mean age was 64.2 years. Data on appraisals, core-relational themes, and
      emotions were collected. Data were analysed using both Spearman's correlation
      tests and multivariate regression modelling. RESULTS: Longitudinal analysis
      demonstrated weak correlation between change scores of theoretically associated
      components and some emotions correlated more strongly with cognitions
      contradicting theoretical expectations. Cross-sectional multivariate testing of
      the ability of cognitions to explain variance in emotion was largely theory
      inconsistent. CONCLUSIONS: Although data support the generic structure of the
      Transactional Model, they question the model specifics. Larger scale research is
      needed encompassing a wider range of emotions and using more complex statistical
      testing. STATEMENT OF CONTRIBUTION: WHAT IS ALREADY KNOWN ON THIS SUBJECT?: *
      Stress processes are transactional and coping outcome is informed by both
      cognitive appraisal of the stressor and the individual's emotional response
      (Lazarus & Folkman, 1984). * Lazarus (1999) made specific hypotheses about which
      particular stress appraisals would determine which emotional response, but only a
      small number of these relationships have been robustly investigated. * Previous
      empirical testing of this theory has been limited by design and statistical
      limitations. WHAT DOES THIS STUDY ADD?: * This study empirically investigates the
      cognitive precedents of a much larger range of emotional outcomes than has
      previously been attempted in the literature. * Support for the model at a general
      level is established: this study demonstrates that both primary and secondary
      appraisals, and core-relational themes are important variables in explaining
      variance in emotional outcome. * The specific hypotheses proposed by Lazarus
      (1999) are not, however, supported: using data-driven approaches we demonstrate
      that equally high levels of variance can be explained using entirely different
      cognitive appraisals than those hypothesized.

PMID- 23006058
TI  - Chronic treatment with tempol does not significantly ameliorate renal tissue
      hypoxia or disease progression in a rodent model of polycystic kidney disease.
AB  - In the present study, we tested whether polycystic kidney disease (PKD) is
      associated with renal tissue hypoxia and oxidative stress, which, in turn,
      contribute to the progression of cystic disease and hypertension. Lewis
      polycystic kidney (LPK) rats and Lewis control (Lewis) rats were treated with
      tempol (1 mmol/L in drinking water) from 3 to 13 weeks of age or remained
      untreated. The LPK rats developed polyuria, uraemia and proteinuria. At 13 weeks
      of age, LPK rats had greater mean arterial pressure (1.5-fold), kidney weight
      (sixfold) and plasma creatinine (3.5-fold) than Lewis rats. Kidneys from LPK rats
      were cystic and fibrotic. Renal hypoxia was evidenced by staining for
      pimonidazole adducts and hypoxia-inducible factor (HIF)-1alpha in cells lining
      renal cysts and upregulation of HIF-1alpha and its downstream targets vascular
      endothelial growth factor (VEGF), glucose transporter-1 (Glut-1) and heme
      oxygenase 1 (HO-1). However, total HO activity did not differ greatly between
      kidney tissue from LPK compared with Lewis rats. Renal oxidative and/or
      nitrosative stress was evidenced by ninefold greater immunofluorescence for 3
      nitrotyrosine in kidney tissue from LPK compared with Lewis rats and a > 10-fold
      upregulation of mRNA for p47phox and gp91phox. Total renal superoxide dismutase
      (SOD) activity was sevenfold less and expression of SOD1 mRNA was 70% less in
      kidney tissue from LPK compared with Lewis rats. In LPK rats, tempol treatment
      reduced immunofluorescence for 3-nitrotyrosine and HIF1A mRNA while upregulating
      VEGF and p47phox mRNA expression, but otherwise had little impact on disease
      progression, renal tissue hypoxia or hypertension. Our findings do not support
      the hypothesis that oxidative stress drives hypoxia and disease progression in
      PKD.

PMID- 23006060
TI  - Changes in sensory dominance during childhood: converging evidence from the
      colavita effect and the sound-induced flash illusion.
AB  - In human adults, visual dominance emerges in several multisensory tasks. In
      children, auditory dominance has been reported up to 4 years of age. To establish
      when sensory dominance changes during development, 41 children (6-7, 9-10, and 11
      12 years) were tested on the Colavita task (Experiment 1) and 32 children (6-7, 9
      10, and 11-12 years) were tested on the sound-induced flash illusion (Experiment
      2). In both experiments, an auditory dominance emerged in 6- to 7-year-old
      children compared to older children. Adult-like visual dominance started to
      emerge from 9 to 10 years of age, and consolidated in 11- to 12-year-old
      children. These findings show that auditory dominance persists up to 6 years, but
      switches to visual dominance during the first school years.

PMID- 23006061
TI  - Aerobic oxidative amidation of aromatic and cinnamic aldehydes with secondary
      amines by CuI/2-pyridonate catalytic system.
AB  - A simple and convenient CuI/2-pyridonate catalytic system for the oxidative
      amidation of aldehydes with secondary amines has been developed. With this
      system, a variety of useful arylamides have been synthesized in moderate to good
      yields in the presence of small amount of copper catalyst and the pyridonate
      ligand, generating only water as a coproduct. Synthesis of cinnamamides was also
      achieved by the reactions of cinnamaldehydes with secondary amines in moderate
      yields. Air was successfully employed as a green oxidant in this catalytic
      system, achieving a safe and atom-efficient system for the synthesis of amides.

PMID- 23006062
TI  - Health consequences of prophylactic exposure to antenatal corticosteroids among
      children born late preterm or term.
AB  - OBJECTIVE: To investigate the duration of effects and health consequences of
      earlier antenatal corticosteroid exposure in infants born late preterm or term.
      DESIGN: Observational cohort study. SETTING: Children born after gestational week
      34 in Sweden, 1976-1997, whose mothers were hospitalized for imminent preterm
      delivery. The children were followed to their 11th birthday. SAMPLE: The cohort
      consisted of 11 873 infants, of whom 8620 were exposed. METHODS: Exposure was
      estimated at hospital level. Infants born at a hospital practicing antenatal
      corticosteroid administration were classified as exposed. Estimation of hospital
      routines was based on questionnaire data, telephone interviews with physicians
      and pharmacy sales, validated in a random sample of medical records. Logistic
      regression was used to assess associations with adjustments for pregnancy length,
      birth year and hospital level. MAIN OUTCOME MEASURES: Rates and odds ratios of
      mortality, respiratory distress syndrome, bronchopulmonary dysplasia, epilepsy,
      cerebral palsy, childhood diabetes, birthweight, length and head circumference
      for all infants, and for preterm and term infants, respectively. RESULTS: Exposed
      infants had reduced risks of respiratory distress syndrome (odds ratio 0.54, 95%
      confidence interval 0.35-0.83) and small head circumference (odds ratio 0.47, 95%
      confidence interval 0.36-0.61), and an increased risk of low Apgar scores (odds
      ratio 1.40, 95% confidence interval 1.01-1.94), most pronounced in infants born
      after gestational week 37. CONCLUSIONS: Infants born after gestational week 34
      seem to benefit from earlier antenatal corticosteroid administration, with
      reduced risks of respiratory distress syndrome. However, the treatment was less
      beneficial for term infants, because they also had increased risk of low Apgar
      scores.

PMID- 23006063
TI  - Prevention of intradialytic hypotension in patients with acute kidney injury
      submitted to sustained low-efficiency dialysis.
AB  - OBJECTIVES: This study evaluated the effects of a protocol aiming to reduce
      hypotension in acute kidney injury (AKI) patients submitted to sustained low
      efficiency dialysis (SLED). METHODS: Patients were randomly assigned to two SLED
      prescriptions-control group, dialysate temperature was 37.0 degrees C with a
      fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and
      profiling group, dialysate temperature was 35.5 degrees C with a variable sodium
      concentration [150-138 mEq/L] and UF rate. RESULTS: Sixty-two SLED sessions were
      evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in
      terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score.
      Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both
      groups. The profiling group had significantly less hypotension episodes (23% vs.
      57% in control, p = 0.009) and achieved higher UF volume (2.23 +/- 1.25 L vs.
      1.59 +/- 1.03 L in control, p = 0.04) when compared with control group.
      CONCLUSIONS: SLED protocol with modulation of dialysate temperature, sodium, and
      UF profiling showed similar efficacy but less intradialytic hypotension when
      compared with a standard SLED prescription.

PMID- 23006064
TI  - 5-Arylidenethioxothiazolidinones as inhibitors of tyrosyl-DNA phosphodiesterase
      I.
AB  - Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the
      irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic
      resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to
      potentiating clinically used Top1 inhibitors. However, despite recent efforts in
      studying Tdp1 as a therapeutic target, its inhibition remains poorly understood
      and largely underexplored. We describe herein the discovery of arylidene
      thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial
      tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies
      we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified
      compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 MUM). Molecular
      modeling provided insight into key interactions essential for observed
      activities. Some derivatives were also active against endogenous Tdp1 in whole
      cell extracts. These findings contribute to advancing the understanding on Tdp1
      inhibition.

PMID- 23006065
TI  - Application of DLVO energy map to evaluate interactions between spherical
      colloids and rough surfaces.
AB  - This study theoretically evaluated interactions between spherical colloids and
      rough surfaces in three-dimensional space using Derjaguin-Landau-Verwey- Overbeek
      (DLVO) energy/force map and curve. The rough surfaces were modeled as a flat
      surface covered by hemispherical protrusions. A modified Derjaguin approach was
      employed to calculate the interaction energies and forces. Results show that more
      irreversible attachments in primary minima occur at higher ionic strengths, which
      theoretically explains the observed hysteresis of colloid attachment and
      detachment during transients in solution chemistry. Secondary minimum depths can
      be increased significantly in concave regions (e.g., areas aside of asperities or
      between asperities) due to sidewall interactions. Through comparing the
      tangential attractive forces from asperities and the hydrodynamic drag forces in
      three-dimensional space, we showed that attachment in secondary minima can be
      located on open collector surfaces of a porous medium. This result challenges the
      usual belief that the attachment in secondary minima only occurs in stagnation
      point regions of the porous medium and is absent in shear flow systems such as
      parallel plate flow chamber and impinging jet apparatus. Despite the argument
      about the role of secondary minima in colloid attachment remained, our study
      theoretically justified the existence of attachment in secondary minima in the
      presence of surface roughness. Further, our study implied that the presence of
      surface roughness is more favorable for attachment in secondary minima than in
      primary minima under unfavorable chemical conditions.

PMID- 23006066
TI  - Estimating open population site occupancy from presence-absence data lacking the
      robust design.
AB  - Many animal monitoring studies seek to estimate the proportion of a study area
      occupied by a target population. The study area is divided into spatially
      distinct sites where the detected presence or absence of the population is
      recorded, and this is repeated in time for multiple seasons. However, when
      occupied sites are detected with probability p < 1, the lack of a detection does
      not imply lack of occupancy. MacKenzie et al. (2003, Ecology 84, 2200-2207)
      developed a multiseason model for estimating seasonal site occupancy (psit )
      while accounting for unknown p. Their model performs well when observations are
      collected according to the robust design, where multiple sampling occasions occur
      during each season; the repeated sampling aids in the estimation p. However,
      their model does not perform as well when the robust design is lacking. In this
      paper, we propose an alternative likelihood model that yields improved seasonal
      estimates of p and Psit in the absence of the robust design. We construct the
      marginal likelihood of the observed data by conditioning on, and summing out, the
      latent number of occupied sites during each season. A simulation study shows that
      in cases without the robust design, the proposed model estimates p with less bias
      than the MacKenzie et al. model and hence improves the estimates of Psit . We
      apply both models to a data set consisting of repeated presence-absence
      observations of American robins (Turdus migratorius) with yearly survey periods.
      The two models are compared to a third estimator available when the repeated
      counts (from the same study) are considered, with the proposed model yielding
      estimates of Psit closest to estimates from the point count model.

PMID- 23006067
TI  - Weak measurements with orbital-angular-momentum pointer states.
AB  - Weak measurements are a unique tool for accessing information about weakly
      interacting quantum systems with minimal back action. Joint weak measurements of
      single-particle operators with pointer states characterized by a two-dimensional
      Gaussian distribution can provide, in turn, key information about quantum
      correlations that can be relevant for quantum information applications. Here we
      demonstrate that by employing two-dimensional pointer states endowed with orbital
      angular momentum (OAM), it is possible to extract weak values of the higher order
      moments of single-particle operators, an inaccessible quantity with Gaussian
      pointer states only. We provide a specific example that illustrates the
      advantages of our method both in terms of signal enhancement and information
      retrieval.

PMID- 23006068
TI  - Are scattering properties of graphs uniquely connected to their shapes?
AB  - The famous question of Kac "can one hear the shape of a drum?" addressing the
      unique connection between the shape of a planar region and the spectrum of the
      corresponding Laplace operator, can be legitimately extended to scattering
      systems. In the modified version, one asks whether the geometry of a vibrating
      system can be determined by scattering experiments. We present the first
      experimental approach to this problem in the case of microwave graphs (networks)
      simulating quantum graphs. Our experimental results strongly indicate a negative
      answer. To demonstrate this we consider scattering from a pair of isospectral
      microwave networks consisting of vertices connected by microwave coaxial cables
      and extended to scattering systems by connecting leads to infinity to form
      isoscattering networks. We show that the amplitudes and phases of the
      determinants of the scattering matrices of such networks are the same within the
      experimental uncertainties. Furthermore, we demonstrate that the scattering
      matrices of the networks are conjugated by the so-called transplantation
      relation.

PMID- 23006069
TI  - Experimental activation of bound entanglement.
AB  - Entanglement is one of the essential resources in quantum information and
      communication technology (QICT). The entanglement thus far explored and applied
      to QICT has been pure and distillable entanglement. Yet, there is another type of
      entanglement, called "bound entanglement," which is not distillable by local
      operations and classical communication. We demonstrate the experimental
      "activation" of the bound entanglement held in the four-qubit Smolin state,
      unleashing its immanent entanglement in distillable form, with the help of
      auxiliary two-qubit entanglement and local operations and classical
      communication. We anticipate that it opens the way to a new class of QICT
      applications that utilize more general classes of entanglement than ever,
      including bound entanglement.

PMID- 23006070
TI  - Quantum entanglement in random physical states.
AB  - Most states in the Hilbert space are maximally entangled. This fact has proven
      useful to investigate--among other things--the foundations of statistical
      mechanics. Unfortunately, most states in the Hilbert space of a quantum many-body
      system are not physically accessible. We define physical ensembles of states
      acting on random factorized states by a circuit of length k of random and
      independent unitaries with local support. We study the typicality of entanglement
      by means of the purity of the reduced state. We find that for a time k=O(1), the
      typical purity obeys the area law. Thus, the upper bounds for area law are
      actually saturated, on average, with a variance that goes to zero for large
      systems. Similarly, we prove that by means of local evolution a subsystem of
      linear dimensions L is typically entangled with a volume law when the time scales
      with the size of the subsystem. Moreover, we show that for large values of k the
      reduced state becomes very close to the completely mixed state.

PMID- 23006071
TI  - Equation of state beyond the radius of convergence of the virial expansion.
AB  - The well-known problem of the virial expansion low-density limitation is
      considered within Mayer's cluster expansion method. The expression for the
      configuration integral and the corresponding equation of state are presented
      based on this approach but not limited by the convergence radius of the series
      for density and activity. When taking into account any number of irreducible
      integrals at the thermodynamic limit, this equation of state demonstrates the
      exact coincidence with the virial one inside the domain of its convergence but
      specifies the condensation process directly outside that domain. Thus, the
      assumption of some researchers that the condensation should appear in the domain
      where the proof of the virial expansion is limited may now be regarded as
      confirmed, exclusively using the classical Gibbs statistics.

PMID- 23006073
TI  - Quantum stability of chameleon field theories.
AB  - Chameleon scalar fields are dark-energy candidates which suppress fifth forces in
      high density regions of the Universe by becoming massive. We consider chameleon
      models as effective field theories and estimate quantum corrections to their
      potentials. Requiring that quantum corrections be small, so as to allow reliable
      predictions of fifth forces, leads to an upper bound m<0.0073(rho/10 g cm(
      3))(1/3) eV for gravitational-strength coupling whereas fifth force experiments
      place a lower bound of m>0.0042 eV. An improvement of less than a factor of two
      in the range of fifth force experiments could test all classical chameleon field
      theories whose quantum corrections are well controlled and couple to matter with
      nearly gravitational strength regardless of the specific form of the chameleon
      potential.

PMID- 23006072
TI  - Evidence of galaxy cluster motions with the kinematic Sunyaev-Zel'dovich effect.
AB  - Using high-resolution microwave sky maps made by the Atacama Cosmology Telescope,
      we for the first time present strong evidence for motions of galaxy clusters and
      groups via microwave background temperature distortions due to the kinematic
      Sunyaev-Zel'dovich effect. Galaxy clusters are identified by their constituent
      luminous galaxies observed by the Baryon Oscillation Spectroscopic Survey, part
      of the Sloan Digital Sky Survey III. We measure the mean pairwise momentum of
      clusters, with a probability of the signal being due to random errors of 0.002,
      and the signal is consistent with the growth of cosmic structure in the standard
      model of cosmology.

PMID- 23006074
TI  - Kaon B parameter from improved staggered fermions in N(f)=2+1 QCD.
AB  - We present a calculation of the kaon B parameter B(K) using lattice QCD. We use
      improved staggered valence and sea fermions, the latter generated by the MILC
      Collaboration with N(f)=2+1 light flavors. To control discretization errors, we
      use four different lattice spacings ranging down to a~0.045 fm. The chiral and
      continuum extrapolations are done using SU(2) staggered chiral perturbation
      theory. Our final result is B(K)=0.727+/-0.004(stat)+/-0.038(syst), where the
      dominant systematic error is from our use of truncated (one-loop) matching
      factors.

PMID- 23006075
TI  - Probing new physics via the B(s)0->MU(+)MU- effective lifetime.
AB  - We have recently seen new upper bounds for B(s)(0)->MU(+)MU(-), a key decay to
      search for physics beyond the standard model. Furthermore a nonvanishing decay
      width difference DeltaGamma(s) of the B(s) system has been measured. We show that
      DeltaGamma(s) affects the extraction of the B(s)(0)->MU(+)MU(-) branching ratio
      and the resulting constraints on the new physics parameter space and give
      formulas for including this effect. Moreover, we point out that DeltaGamma(s)
      provides a new observable, the effective B(s)(0)->MU(+)MU(-) lifetime
      tau(MU(+)MU(-)), which offers a theoretically clean probe for new physics
      searches that is complementary to the branching ratio. Should the B(s)(0)
      >MU(+)MU(-) branching ratio agree with the standard model, the measurement of
      tau(MU(+)MU(-)), which appears feasible at upgrades of the Large Hadron Collider
      experiments, may still reveal large new physics effects.

PMID- 23006076
TI  - Four-jet production at the Large Hadron Collider at next-to-leading order in QCD.
AB  - We present the cross sections for production of up to four jets at the Large
      Hadron Collider, at next-to-leading order in the QCD coupling. We use the
      BLACKHAT library in conjunction with SHERPA and a recently developed algorithm
      for assembling primitive amplitudes into color-dressed amplitudes. We adopt the
      cuts used by ATLAS in their study of multijet events in pp collisions at ?s=7
      TeV. We include estimates of nonperturbative corrections and compare to ATLAS
      data. We store intermediate results in a framework that allows the inexpensive
      computation of additional results for different choices of scale or parton
      distributions.

PMID- 23006077
TI  - Eliminating the renormalization scale ambiguity for top-pair production using the
      principle of maximum conformality.
AB  - It is conventional to choose a typical momentum transfer of the process as the
      renormalization scale and take an arbitrary range to estimate the uncertainty in
      the QCD prediction. However, predictions using this procedure depend on the
      renormalization scheme, leave a nonconvergent renormalon perturbative series, and
      moreover, one obtains incorrect results when applied to QED processes. In
      contrast, if one fixes the renormalization scale using the principle of maximum
      conformality (PMC), all nonconformal {beta(i)} terms in the perturbative
      expansion series are summed into the running coupling, and one obtains a unique,
      scale-fixed, scheme-independent prediction at any finite order. The PMC scale
      MU(R)(PMC) and the resulting finite-order PMC prediction are both to high
      accuracy independent of the choice of initial renormalization scale MU(R)(init),
      consistent with renormalization group invariance. As an application, we apply the
      PMC procedure to obtain next-to-next-to-leading-order (NNLO) predictions for the
      tt-pair production at the Tevatron and LHC colliders. The PMC prediction for the
      total cross section sigma(tt) agrees well with the present Tevatron and LHC data.
      We also verify that the initial scale independence of the PMC prediction is
      satisfied to high accuracy at the NNLO level: the total cross section remains
      almost unchanged even when taking very disparate initial scales MU(R)(init) equal
      to m(t), 20m(t), and ?s. Moreover, after PMC scale setting, we obtain
      A(FB)(tt)?12.5%, A(FB)(pp)?8.28% and A(FB)(tt)(M(tt)>450 GeV)?35.0%. These
      predictions have a 1sigma deviation from the present CDF and D0 measurements; the
      large discrepancy of the top quark forward-backward asymmetry between the
      standard model estimate and the data are, thus, greatly reduced.

PMID- 23006080
TI  - Limits on neutrino masses from neutrinoless double-beta decay.
AB  - Neutrinoless double-beta decay is of fundamental importance for the determining
      neutrino mass. By combining a calculation of nuclear matrix elements within the
      framework of the microscopic interacting boson model with an improved calculation
      of phase space factors, we set limits on the average light neutrino mass and on
      the average inverse heavy neutrino mass (flavor-violating parameter).

PMID- 23006079
TI  - High-precision measurement of the 19Ne half-life and implications for right
      handed weak currents.
AB  - We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262+/
      0.007 s. This result disagrees with the most recent precision measurements and is
      important for placing bounds on predicted right-handed interactions that are
      absent in the current standard model. We are able to identify and disentangle two
      competing systematic effects that influence the accuracy of such measurements.
      Our findings prompt a reassessment of results from previous high-precision
      lifetime measurements that used similar equipment and methods.

PMID- 23006081
TI  - Characteristic spectrum of very low-energy photoelectron from above-threshold
      ionization in the tunneling regime.
AB  - We report an experimental and theoretical study of very low-energy photoelectrons
      in tunneling ionization process from noble gas atoms interacting with ultrashort
      intense infrared laser pulses. A universal peak structure with electron energy
      well below 1 eV in the photoelectron spectrum, corresponding to the double-hump
      structure in the longitudinal momentum distribution, is identified experimentally
      for all atomic species. Our quantum and semiclassical analysis reveal the role of
      long-range Coulomb potential in the production of this very low-energy peak
      structure.

PMID- 23006082
TI  - Adiabatic state preparation of interacting two-level systems.
AB  - We consider performing adiabatic rapid passage (ARP) using frequency-swept
      driving pulses to excite a collection of interacting two-level systems. Such a
      model arises in a wide range of many-body quantum systems, such as cavity QED or
      quantum dots, where a nonlinear component couples to light. We analyze the one
      dimensional case using the Jordan-Wigner transformation, as well as the mean
      field limit where the system is described by a Lipkin-Meshkov-Glick Hamiltonian.
      These limits provide complementary insights into the behavior of many-body
      systems under ARP, suggesting our results are generally applicable. We
      demonstrate that ARP can be used for state preparation in the presence of
      interactions, and identify the dependence of the required pulse shapes on the
      interaction strength. In general, interactions increase the pulse bandwidth
      required for successful state transfer, introducing new restrictions on the pulse
      forms required.

PMID- 23006083
TI  - Quantum resonances in selective rotational excitation of molecules with a
      sequence of ultrashort laser pulses.
AB  - We experimentally investigate the effect of quantum resonance in the rotational
      excitation of the simplest quantum rotor--a diatomic molecule. Using the
      techniques of high-resolution femtosecond pulse shaping and rotational state
      resolved detection, we measure directly the amount of energy absorbed by
      molecules interacting with a periodic train of laser pulses, and study their
      dependence on the train period. We show that the energy transfer is significantly
      enhanced at quantum resonance, and use this effect to demonstrate selective
      rotational excitation of two nitrogen isotopologs, (14)N(2) and (15)N(2).
      Moreover, by tuning the period of the pulse train in the vicinity of a fractional
      quantum resonance, we achieve selective rotational excitation of para- and ortho
      isomers of (15)N(2).

PMID- 23006084
TI  - Strong-field ionization rate depends on the sign of the magnetic quantum number.
AB  - We report the first experimental observation of the dependence of strong-field
      ionization rate on the sign of the magnetic quantum number. We measure the strong
      field sequential double ionization yield of argon by two time-delayed near
      circularly polarized laser pulses. It is found that double-ionization yield is
      enhanced more than 3 times if two lasers have the opposite helicities. Analysis
      shows that the single ionization of both the neutral and ion prefer the same sign
      of the magnetic quantum number. A qualitative and intuitive model is proposed to
      help understand this phenomenon.

PMID- 23006085
TI  - Absolute measurement of the relativistic magnetic dipole transition energy in
      heliumlike argon.
AB  - The 1s2s (3)S(1)->1s(2) (1)S(0) relativistic magnetic dipole transition in
      heliumlike argon, emitted by the plasma of an electron-cyclotron resonance ion
      source, has been measured using a double-flat crystal x-ray spectrometer. Such a
      spectrometer, used for the first time on a highly charged ion transition,
      provides absolute (reference-free) measurements in the x-ray domain. We find a
      transition energy of 3104.1605(77) eV (2.5 ppm accuracy). This value is the most
      accurate, reference-free measurement done for such a transition and is in good
      agreement with recent QED predictions.

PMID- 23006086
TI  - Spin dynamics in the Kapitza-Dirac effect.
AB  - Electron spin dynamics in Kapitza-Dirac scattering from a standing laser wave of
      high frequency and high intensity is studied. We develop a fully relativistic
      quantum theory of the electron motion based on the time-dependent Dirac equation.
      Distinct spin dynamics, with Rabi oscillations and complete spin-flip
      transitions, is demonstrated for Kapitza-Dirac scattering involving three photons
      in a parameter regime accessible to future high-power x-ray laser sources. The
      Rabi frequency and, thus, the diffraction pattern is shown to depend crucially on
      the spin degree of freedom.

PMID- 23006087
TI  - Noiseless optical amplifier operating on hundreds of spatial modes.
AB  - We implement a noiseless optical amplifier using a phase-sensitive four-wave
      mixing process in rubidium vapor. We observe performance near the quantum limit
      for this type of amplifier over a range of experimental parameters and show that
      the noise figure is always better than would be obtained with a phase-insensitive
      amplifier with the same gain. Additionally, we observe that the amplifier
      supports hundreds of spatial modes, making it possible to amplify complex two
      dimensional spatial patterns with less than a 10% degradation of the input signal
      to-noise ratio for gains up to 4.6. To confirm the multimode character of the
      amplifier, we study the noise figure as a function of spatially-varying losses.
      Additionally, we investigate the spatial resolution of the amplifier and show
      that it supports a range of spatial frequencies from 1.3 to more than 35 line
      pairs per millimeter.

PMID- 23006088
TI  - Depolarization remote sensing by orthogonality breaking.
AB  - A new concept devoted to sensing the depolarization strength of materials from a
      single measurement is proposed and successfully validated on a variety of
      samples. It relies on the measurement of the orthogonality breaking between two
      orthogonal states of polarization after interaction with the material to be
      characterized. Due to orthogonality preservation between the two states after
      propagation in birefringent media, this measurement concept is shown to be
      perfectly suited to depolarization remote sensing through fibers, opening the way
      to real-time depolarization endoscopy.

PMID- 23006089
TI  - Ultrafast and octave-spanning optical nonlinearities from strongly phase
      mismatched quadratic interactions.
AB  - Cascaded nonlinearities have attracted much interest, but ultrafast applications
      have been seriously hampered by the simultaneous requirements of being near phase
      matching and having ultrafast femtosecond response times. Here we show that in
      strongly phase-mismatched nonlinear frequency conversion crystals the pump pulse
      can experience a large and extremely broadband self-defocusing cascaded Kerr-like
      nonlinearity. The large cascaded nonlinearity is ensured through interaction with
      the largest quadratic tensor element in the crystal, and the strong phase
      mismatch ensures an ultrafast nonlinear response with an octave-spanning
      bandwidth. We verify this experimentally by showing few-cycle soliton compression
      with noncritical cascaded second-harmonic generation: Energetic 47 fs infrared
      pulses are compressed in a just 1-mm long bulk lithium niobate crystal to 17 fs
      (under 4 optical cycles) with 80% efficiency, and upon further propagation an
      octave-spanning supercontinuum is observed. Such ultrafast cascading is expected
      to occur for a broad range of pump wavelengths spanning the near- and mid-IR
      using standard nonlinear crystals.

PMID- 23006090
TI  - Adjoint method provides phase response functions for delay-induced oscillations.
AB  - Limit-cycle oscillations induced by time delay are widely observed in various
      systems, but a systematic phase-reduction theory for them has yet to be
      developed. Here we present a practical theoretical framework to calculate the
      phase response function Z(theta), a fundamental quantity for the theory, of delay
      induced limit cycles with infinite-dimensional phase space. We show that Z(theta)
      can be obtained as a zero eigenfunction of the adjoint equation associated with
      an appropriate bilinear form for the delay differential equations. We confirm the
      validity of the proposed framework for two biological oscillators and demonstrate
      that the derived phase equation predicts intriguing multimodal locking behavior.

PMID- 23006078
TI  - First observation of the M1 transition psi(3686)->gammaeta(c)(2S).
AB  - Using a sample of 106*10(6) psi(3686) events collected with the BESIII detector
      at the BEPCII storage ring, we have made the first measurement of the M1
      transition between the radially excited charmonium S-wave spin-triplet and the
      radially excited S-wave spin-singlet states: psi(3686)->gammaeta(c)(2S). Analyses
      of the processes psi(3686)->gammaeta(c)(2S) with eta(c)(2S)->K(S)(0)K(+/-)pi(?)
      and K(+)K(-)pi(0) give an eta(c)(2S) signal with a statistical significance of
      greater than 10 standard deviations under a wide range of assumptions about the
      signal and background properties. The data are used to obtain measurements of the
      eta(c)(2S) mass (M(eta(c)(2S))=3637.6+/-2.9(stat)+/-1.6(syst) MeV/c(2)), width
      (Gamma(eta(c)(2S))=16.9+/-6.4(stat)+/-4.8(syst) MeV), and the product branching
      fraction (B(psi(3686)->gammaeta(c)(2S))*B(eta(c)(2S)->KKpi)=(1.30+/-0.20(stat)+/
      0.30(syst))*10(-5)). Combining our result with a BABAR measurement of
      B(eta(c)(2S)->KKpi), we find the branching fraction of the M1 transition to be
      B(psi(3686)->gammaeta(c)(2S))=(6.8+/-1.1(stat)+/-4.5(syst))*10(-4).

PMID- 23006091
TI  - Solutions of the vector nonlinear Schrodinger equations: evidence for
      deterministic rogue waves.
AB  - We construct and discuss a semirational, multiparametric vector solution of
      coupled nonlinear Schrodinger equations (Manakov system). This family of
      solutions includes known vector Peregrine solutions, bright- and dark-rogue
      solutions, and novel vector unusual freak waves. The vector rogue waves could be
      of great interest in a variety of complex systems, from optics and fluid dynamics
      to Bose-Einstein condensates and finance.

PMID- 23006092
TI  - Homogeneous nucleation in water in microfluidic channels.
AB  - It has been an experimental challenge to test the rupture of liquids with
      homogeneous nucleation of vapor bubbles. Many prior studies suffered from the
      ubiquitous presence of impurities in liquids or at container surfaces that
      spontaneously nucleate and grow under tension. Here, we propose a microfluidic
      approach to eliminate such impurities and obtain homogeneous bubble nucleation.
      We stretch the liquid dynamically via the interaction between a laser-induced
      shock and an air-liquid interface in a microchannel. Reproducible observations of
      the nucleation of vapor bubbles are obtained, supporting our claim of homogeneous
      nucleation. From comparisons of the distribution of vapor cavities with Euler
      flow simulations, the nucleation threshold for water at room temperature is
      predicted to be -60 MPa.

PMID- 23006093
TI  - High-harmonic fast-wave power flow along magnetic field lines in the scrape-off
      layer of NSTX.
AB  - A significant fraction of high-harmonic fast-wave (HHFW) power applied to NSTX
      can be lost to the scrape-off layer (SOL) and deposited in bright and hot spirals
      on the divertor rather than in the core plasma. We show that the HHFW power flows
      to these spirals along magnetic field lines passing through the SOL in front of
      the antenna, implying that the HHFW power couples across the entire width of the
      SOL rather than mostly at the antenna face. This result will help guide future
      efforts to understand and minimize these edge losses in order to maximize fast
      wave heating and current drive.

PMID- 23006094
TI  - Activated nucleation of vortices in a dipole-blockaded supersolid condensate.
AB  - We investigate theoretically and numerically a model of a supersolid in a dipole
      blockaded Bose-Einstein condensate. The dependence of the superfluid fraction
      with an imposed thermal bath and a uniform boost velocity on the condensate is
      considered. Specifically, we observe a critical velocity for the nucleation of
      vortices in our system that is strongly linked to a steplike decrease in the
      superfluid fraction. We are able to use a scaling argument based on the energy
      required to activate a vortex, relating the critical temperature to the critical
      velocity, and find that this relationship is in good agreement with the numerical
      simulations carried out on the nonlocal Gross-Pitaevskii equation.

PMID- 23006095
TI  - Interaction-induced impeding of decoherence and anomalous diffusion.
AB  - We study how the interplay of dissipation and interactions affects the dynamics
      of a bosonic many-body quantum system. In the presence of both dissipation and
      strongly repulsive interactions, observables such as the coherence and the
      density fluctuations display three dynamical regimes: an initial exponential
      variation followed by a power-law regime, and finally a slow exponential
      convergence to their asymptotic values. These very long-time scales arise as
      dissipation forces the population of states disfavored by interactions. The long
      time, strong coupling dynamics are understood by performing a mapping onto a
      classical diffusion process displaying non-Brownian behavior. While both
      dissipation and strong interactions tend to suppress coherence when acting
      separately, we find that strong interaction impedes the decoherence process
      generated by the dissipation.

PMID- 23006096
TI  - Mass flux characteristics in solid 4He for T>100 mK: evidence for bosonic
      Luttinger-liquid behavior.
AB  - At a pressure of ~25.7 bar, the flux F carried by solid (4)He for T>100 mK
      depends on the net chemical potential difference between two reservoirs in series
      with the solid, DeltaMU, and obeys F~(DeltaMU)(b), where b~0.3 is independent of
      temperature. At fixed DeltaMU the temperature dependence of the flux F can be
      adequately represented by F~-ln(T/tau), tau~0.6 K, for 0.1<=T<=0.5 K. A single
      function F=F(0)(DeltaMU)(b)ln(T/tau) fits all of the available data sets in the
      range 25.6-25.8 bar reasonably well. We suggest that the mass flux in solid (4)He
      for T>100 mK may have a Luttinger liquidlike behavior in this bosonic system.

PMID- 23006097
TI  - Quantum confinement drives macroscopic stress oscillations at the initial stage
      of thin film growth.
AB  - Functionalization of thin-film heterostructures on the basis of their electrical,
      optical and magnetic properties, requires precise control of the film stresses
      that develop during the growth process. By using real-time in situ stress
      measurements, the present study reveals strikingly that the in-plane film stress
      oscillates with increasing film thickness at the initial stage of epitaxial
      Al(111) film growth on a Si(111)-?3*?3-Al surface, with a periodicity of 2 times
      the Fermi wavelength of bulk Al and a stress variation from maximum to minimum as
      large as 100 MPa. Such macroscopic stress oscillations are shown to be caused by
      quantum confinement of the free electrons in the ultrathin epitaxial metal film.
      The amplitude, period, and phase of the observed stress oscillations are
      consistent with predictions based on the free electron model and continuum
      elasticity.

PMID- 23006098
TI  - Thermodynamic study of simple molecular glasses: universal features in their heat
      capacity and the size of the cooperatively rearranging regions.
AB  - We have obtained some universal thermodynamic properties on glass transitions of
      molecular liquids. The heat capacity C(p) of glassy propene, which was vitrified
      by using a vapor-deposition technique, was measured with a newly developed
      adiabatic calorimeter. Propene has the lowest glass transition temperature
      (T(g)=56 K), the largest C(p) jump at T(g) (C(p)(lq)/C(p)(gl)~2.5), and the
      lowest residual entropy (S(res)~Rln2) compared with glass-forming molecules
      measured before. We have analyzed the present data with other hydrocarbon
      molecules vitrified by liquid quenching and obtained the following results: (1)
      The excess heat capacities are scaled well by using a Kauzmann temperature T(K),
      (2) The size of the cooperative rearrangement region (CRR) frozen at T(g)
      increases with decreasing the temperature difference between T(g) and T(K)
      (Kauzmann temperature), and (3) The simpler the molecule is, the larger the
      frozen CRR becomes. These are all supporting the validity of the Adam-Gibbs
      theory.

PMID- 23006099
TI  - Determining the in-plane orientation of the ground-state orbital of CeCu2Si2.
AB  - We have successfully determined the hitherto unknown sign of the B(4)(4) Stevens
      crystal-field parameter of the tetragonal heavy-fermion compound CeCu(2)Si(2)
      using vector q-dependent nonresonant inelastic x-ray scattering experiments at
      the cerium N(4,5) edge. The observed difference between the two different
      directions, q?[100] and q?[110], is due to the anisotropy of the crystal-field
      ground state in the (001) plane and is observable only because of the utilization
      of higher than dipole transitions possible in nonresonant inelastic x-ray
      scattering. This approach allows us to go beyond the specific limitations of dc
      magnetic susceptibility, inelastic neutron scattering, and soft x-ray
      spectroscopy, and provides us with a reliable information about the orbital state
      of the 4f electrons relevant for the quantitative modeling of the quasiparticles
      and their interactions in heavy-fermion systems.

PMID- 23006100
TI  - Exciton Mott transition in Si revealed by terahertz spectroscopy.
AB  - We investigate the exciton Mott transition in Si by using optical pump and
      terahertz probe spectroscopy. The density-dependent exciton ionization ratio
      alpha is quantitatively evaluated from the analysis of dielectric function and
      conductivity spectra. The Mott density is clearly determined by the rapid
      increase in alpha as a function of electron-hole (e-h) pair density, which agrees
      well with the value expected from the random phase approximation theory. However,
      exciton is sustained in the high-density metallic region above the Mott density
      as manifested by the 1s-2p excitonic resonance that remains intact across the
      Mott density. Moreover, the charge carrier scattering rate is strongly enhanced
      slightly above the Mott density due to nonvanishing excitons, indicating the
      emergence of highly correlated metallic phase in the photoexcited e-h system.
      Concomitantly, the loss function spectra exhibit the signature of plasmon-exciton
      coupling, i.e., the existence of a new collective mode of charge density
      excitation combined with the excitonic polarization at the proximity of Mott
      density.

PMID- 23006101
TI  - Phonon self-energy corrections to nonzero wave-vector phonon modes in single
      layer graphene.
AB  - Phonon self-energy corrections have mostly been studied theoretically and
      experimentally for phonon modes with zone-center (q=0) wave vectors. Here, gate
      modulated Raman scattering is used to study phonons of a single layer of graphene
      originating from a double-resonant Raman process with q?0. The observed phonon
      renormalization effects are different from what is observed for the zone-center
      q=0 case. To explain our experimental findings, we explored the phonon self
      energy for the phonons with nonzero wave vectors (q?0) in single-layer graphene
      in which the frequencies and decay widths are expected to behave oppositely to
      the behavior observed in the corresponding zone-center q=0 processes. Within this
      framework, we resolve the identification of the phonon modes contributing to the
      G(?) Raman feature at 2450 cm(-1) to include the iTO+LA combination modes with
      q?0 and also the 2iTO overtone modes with q=0, showing both to be associated with
      wave vectors near the high symmetry point K in the Brillouin zone.

PMID- 23006102
TI  - Circularly polarized photoluminescence as a probe of density of states in
      GaAs/AlGaAs quantum Hall bilayers.
AB  - Polarized magnetophotoluminescence is employed to study the energies and
      occupancies of four lowest Landau levels in a couple quantum Hall GaAs/AlGaAs
      double quantum well. As a result, a magnetic field-induced redistribution of
      charge over the Landau levels manifesting to the continuous formation of the
      charge density wave and direct evidence for the symmetric-antisymmetric gap
      shrinkage at nu=3 are found. The observed interlayer charge exchange causes
      depolarization of the ferromagnetic ground state.

PMID- 23006103
TI  - Canted antiferromagnetic phase of the nu=0 quantum Hall state in bilayer
      graphene.
AB  - Motivated to understand the nature of the strongly insulating nu=0 quantum Hall
      state in bilayer graphene, we develop the theory of the state in the framework of
      quantum Hall ferromagnetism. The generic phase diagram, obtained in the presence
      of the isospin anisotropy, perpendicular electric field, and Zeeman effect,
      consists of the spin-polarized ferromagnetic (F), canted antiferromagnetic (CAF),
      and partially (PLP) and fully (FLP) layer-polarized phases. We address the edge
      transport properties of the phases. Comparing our findings with the recent data
      on suspended dual-gated devices, we conclude that the insulating nu=0 state
      realized in bilayer graphene at lower electric field is the CAF phase. We also
      predict a continuous and a sharp insulator-metal phase transition upon tilting
      the magnetic field from the insulating CAF and FLP phases, respectively, to the F
      phase with metallic edge conductance 2e(2)/h, which could be within the reach of
      available fields and could allow one to identify and distinguish the phases
      experimentally.

PMID- 23006104
TI  - Anisotropy of electrical transport in pnictide superconductors studied using
      Monte Carlo simulations of the spin-fermion model.
AB  - An undoped three-orbital spin-fermion model for the Fe-based superconductors is
      studied via Monte Carlo techniques in two-dimensional clusters. At low
      temperatures, the magnetic and one-particle spectral properties are in agreement
      with neutron and photoemission experiments. Our main results are the resistance
      versus temperature curves that display the same features observed in BaFe(2)As(2)
      detwinned single crystals (under uniaxial stress), including a low-temperature
      anisotropy between the two directions followed by a peak at the magnetic ordering
      temperature, that qualitatively appears related to short-range spin order and
      concomitant Fermi surface orbital order.

PMID- 23006105
TI  - Vibrating-coil magnetometry of the spin liquid properties of Tb2Ti2O7.
AB  - We have explored the spin liquid state in Tb(2)Ti(2)O(7) with vibrating-coil
      magnetometry down to ~0.04 K under magnetic fields up to 5 T. We observe magnetic
      history dependence below T*~0.2 K reminiscent of the classical spin ice systems
      Ho(2)Ti(2)O(7) and Dy(2)TiTi(2)O(7). The magnetic phase diagram inferred from the
      magnetization is essentially isotropic, without evidence of magnetization
      plateaus as anticipated for so-called quantum spin ice, predicted theoretically
      for [111] when quantum fluctuations renormalize the interactions. Instead, the
      magnetization for T?T* agrees semiquantitatively with the predictions of "all-in
      all-out" (AIAO) antiferromagnetism. Taken together, this suggests that the spin
      liquid state in Tb(2)Ti(2)O(7) is akin to an incipient AIAO antiferromagnet.

PMID- 23006106
TI  - Mapping of electron-hole excitations in the charge-density-wave system 1T-TiSe2
      using resonant inelastic x-ray scattering.
AB  - In high-resolution resonant inelastic x-ray scattering at the Ti L edge of the
      charge-density-wave system 1T-TiSe(2), we observe sharp low energy loss peaks
      from electron-hole pair excitations developing at low temperature. These
      excitations are strongly dispersing as a function of the transferred momentum of
      light. We show that the unoccupied bands close to the Fermi level can effectively
      be probed in this broadband material. Furthermore, we extract the order parameter
      of the charge-density-wave phase from temperature-dependent measurements.

PMID- 23006107
TI  - Evidence of sharp and diffuse domain walls in BiFeO3 by means of unit-cell-wise
      strain and polarization maps obtained with high resolution scanning transmission
      electron microscopy.
AB  - Domain walls (DWs) substantially influence a large number of applications
      involving ferroelectric materials due to their limited mobility when shifted
      during polarization switching. The discovery of greatly enhanced conduction at
      BiFeO(3) DWs has highlighted yet another role of DWs as a local material state
      with unique properties. However, the lack of precise information on the local
      atomic structure is still hampering microscopical understanding of DW properties.
      Here, we examine the atomic structure of BiFeO(3) 109 degrees  DWs with pm
      precision by a combination of high-angle annular dark-field scanning transmission
      electron microscopy and a dedicated structural analysis. By measuring
      simultaneously local polarization and strain, we provide direct experimental
      proof for the straight DW structure predicted by ab initio calculations as well
      as the recently proposed theory of diffuse DWs, thus resolving a long-standing
      discrepancy between experimentally measured and theoretically predicted DW
      mobilities.

PMID- 23006108
TI  - Ultrahigh-resolution magnetic resonance in inhomogeneous magnetic fields: two
      dimensional long-lived-coherence correlation spectroscopy.
AB  - A half-century quest for improving resolution in Nuclear Magnetic Resonance (NMR)
      and Magnetic Resonance Imaging (MRI) has enabled the study of molecular
      structures, biological interactions, and fine details of anatomy. This progress
      largely relied on the advent of sophisticated superconducting magnets that can
      provide stable and homogeneous fields with temporal and spatial variations below
      DeltaB(0)/B(0)<0.01 ppm. In many cases however, inherent properties of the
      objects under investigation, pulsating arteries, breathing lungs, tissue-air
      interfaces, surgical implants, etc., lead to fluctuations and losses of local
      homogeneity. A new method dubbed "long-lived-coherence correlation spectroscopy"
      (LLC-COSY) opens the way to overcome both inhomogeneous and homogeneous
      broadening, which arise from local variations in static fields and fluctuating
      dipole-dipole interactions, respectively. LLC-COSY makes it possible to obtain
      ultrahigh resolution two-dimensional spectra, with linewidths on the order of
      Deltanu=0.1 to 1 Hz, even in very inhomogeneous fields (DeltaB(0)/B(0)>10 ppm or
      5000 Hz at 9.7 T), and can improve resolution by a factor up to 9 when the
      homogeneous linewidths are determined by dipole-dipole interactions. The
      resulting LLC-COSY spectra display chemical shift differences and scalar
      couplings in two orthogonal dimensions, like in "J spectroscopy." LLC-COSY does
      not require any sophisticated gradient switching or frequency-modulated pulses.
      Applications to in-cell NMR and to magnetic resonance spectroscopy (MRS) of
      selected volume elements in MRI appear promising, particularly when
      susceptibility variations tend to preclude high resolution.

PMID- 23006109
TI  - Pathway-based mean-field model for Escherichia coli chemotaxis.
AB  - We develop a mean-field theory for Escherichia coli chemotaxis based on the
      coupled spatiotemporal dynamics of the cell population and the mean receptor
      methylation level field. This multiscale model connects the cells' population
      level motility behavior with the molecular level pathway dynamics. It reveals a
      simple scaling dependence of the chemotaxis velocity on the adaptation rate in
      exponential gradients. It explains the molecular origin of a maximum chemotaxis
      velocity. Simulations of our model in various spatiotemporal stimuli profiles
      show quantitative agreements with experiments. Moreover, it predicts a surprising
      reversal of chemotaxis group velocity in traveling wave environments. Our
      approach may be used to bridge molecular level pathway dynamics with cellular
      behavior in other biological systems.

PMID- 23006111
TI  - Functional strain-line pattern in the human left ventricle.
AB  - Analysis of deformations in terms of principal directions appears well suited for
      biological tissues that present an underlying anatomical structure of fiber
      arrangement. We applied this concept here to study deformation of the beating
      heart in vivo analyzing 30 subjects that underwent accurate three-dimensional
      echocardiographic recording of the left ventricle. Results show that strain
      develops predominantly along the principal direction with a much smaller
      transversal strain, indicating an underlying anisotropic, one-dimensional
      contractile activity. The strain-line pattern closely resembles the helical
      anatomical structure of the heart muscle. These findings demonstrate that cardiac
      contraction occurs along spatially variable paths and suggest a potential
      clinical significance of the principal strain concept for the assessment of
      mechanical cardiac function. The same concept can help in characterizing the
      relation between functional and anatomical properties of biological tissues, as
      well as fiber-reinforced engineered materials.

PMID- 23006110
TI  - Estimation theoretic measure of resolution for stochastic localization
      microscopy.
AB  - One approach to super-resolution fluorescence microscopy, termed stochastic
      localization microscopy, relies on the nanometer scale spatial localization of
      individual fluorescent emitters that stochastically label specific features of
      the specimen. The precision of emitter localization is an important determinant
      of the resulting image resolution but is insufficient to specify how well the
      derived images capture the structure of the specimen. We address this deficiency
      by considering the inference of specimen structure based on the estimated emitter
      locations. By using estimation theory, we develop a measure of spatial resolution
      that jointly depends on the density of the emitter labels, the precision of
      emitter localization, and prior information regarding the spatial frequency
      content of the labeled object. The Nyquist criterion does not set the scaling of
      this measure with emitter number. Given prior information and a fixed emitter
      labeling density, our resolution measure asymptotes to a finite value as the
      precision of emitter localization improves. By considering the present
      experimental capabilities, this asymptotic behavior implies that further
      resolution improvements require increases in labeling density above typical
      current values. Our treatment also yields algorithms to enhance reliable image
      features. Overall, our formalism facilitates the rigorous statistical
      interpretation of the data produced by stochastic localization imaging
      techniques.

PMID- 23006112
TI  - Unifying microscopic mechanism for pressure and cold denaturations of proteins.
AB  - We study the stability of globular proteins as a function of temperature and
      pressure through NPT simulations of a coarse-grained model. We reproduce the
      elliptical stability of proteins and highlight a unifying microscopic mechanism
      for pressure and cold denaturations. The mechanism involves the solvation of
      nonpolar residues with a thin layer of water. These solvated states have lower
      volume and lower hydrogen-bond energy compared to other conformations of nonpolar
      solutes. Hence, these solvated states are favorable at high pressure and low
      temperature, and they facilitate protein unfolding under these thermodynamical
      conditions.

PMID- 23006113
TI  - Quantifying screening ion excesses in single-molecule force-extension
      experiments.
AB  - We derive a thermodynamic identity that allows one to infer the change in the
      number of screening ions that are associated with a charged macromolecule as the
      macromolecule is continuously stretched. Applying this identity to force
      extension data on both single-stranded and double-stranded DNA, we find that the
      number of polymer-associated ions depends nontrivially on both the bulk salt
      concentration and the bare rigidity of the polymer, with single-stranded DNA
      exhibiting a relatively large decrease in ion excess upon stretching. We
      rationalize these observations using simple models for polyelectrolyte extension.

PMID- 23006114
TI  - Structure and dynamics of loosely cross-linked ionic microgel dispersions in the
      fluid regime.
AB  - We report a comprehensive experimental-theoretical study of the temperature- and
      concentration-dependent swelling behavior of weakly cross-linked PNiPAm ionic
      microgel particles in the deionized fluid phase. The particles swell reversibly
      when the dispersion is cooled from the collapsed state to lower temperatures.
      While the collapsed state shows no dependence on the microgel number density, the
      swelling at lower T is more pronounced at lower concentrations. The static pair
      correlations and short-time diffusion functions, and the concentration and
      temperature dependence of the microgel radius and effective charge, are studied
      using static and dynamic light scattering in combination with state-of-the-art
      analytical theoretical schemes based on a Yukawa-type effective pair potential
      and a core-shell model. We show that only such a combined, simultaneous fit of
      static and dynamic scattering functions allows for an unambiguous determination
      of the microgel radius and effective charge.

PMID- 23006115
TI  - Comment on "Direct observation of charge ordering in magnetite using resonant
      multiwave x-ray diffraction".

PMID- 23006116
TI  - Treatment resistance and psychodynamic psychiatry: concepts psychiatry needs from
      psychoanalysis.
AB  - Over the last 30 years psychiatry and psychoanalysis have moved in substantially
      divergent directions. Psychiatry has become rich in methodology but conceptually
      limited, with a drift toward biological reductionism. Psychoanalysis has remained
      relatively limited in methodology, but conceptually rich. The rich methodology of
      psychiatry has led to major contributions in discovering gene by environment
      interactions, the importance of early adversity, and to recognition of the
      serious problem posed by treatment resistance. However, psychiatry's biologically
      reductionistic conceptual focus interferes with the development of a nuanced
      clinical perspective based on emerging knowledge that might help more treatment
      resistant patients become treatment responders. This article argues that
      recognition of the problem of treatment resistance in psychiatry creates a need
      for it to reconnect with the conceptual richness of psychoanalysis in order to
      improve patient care. Psychodynamic psychiatry is defined as the relevant
      intersection of psychiatry and psychoanalysis where this reconnection can occur.
      I will suggest selected aspects of psychoanalysis that are especially relevant to
      psychiatry in improving outcomes in work with treatment resistant patients.

PMID- 23006117
TI  - Freud: darkness and vision.
AB  - Freud's creation of psychoanalysis is the starting place for a great many forms
      of contemporary psychodynamic psychotherapy, despite the fact that his work is
      very much a mixture of brilliant insights and misconceptions. Here, I will
      attempt to describe both the valuable contributions and the wrong turns, and to
      show how both can be understood in terms of the traumas he suffered as a child,
      as well as his particular adaptations to them. A review of his treatment of a
      number of patients will illustrate this discussion.

PMID- 23006118
TI  - The adaptive functions of sexual plasticity: the suppression and surreptitious
      expression of human sociosexuality.
AB  - Tendencies toward non-monogamy and bisexual expression may constitute primate
      wide predispositions that have been conserved in humans. This observation is
      supported by studies of sexual development and behavior in our primate relatives
      and sexually permissive premodern tribal cultures including hunter-gatherers.
      Nevertheless, even in sexually permissive societies, there may be considerable
      sexual possessiveness and jealousy as well as attempts at parental control of
      children's marital choices. This is associated with punitive revenge against
      unfaithful spouses and mate poaching rivals and parent/offspring conflict around
      marital choices. There is no paradise lost despite the greater sexual freedom.
      Humans may be adaptively designed to suppress each other's sexuality due to
      sexual jealousy and parental desires to control children's sexuality but also to
      surreptitiously evade those restrictions, though there is considerable cross
      cultural variability in the level of sexual restrictiveness.

PMID- 23006119
TI  - Do psychopharmacologists speak to psychotherapists? A survey of practicing
      clinicians.
AB  - BACKGROUND: Split-treatment, the provision of psychotherapy and psychotropic
      medication by two different professionals, has become prevalent in U.S. mental
      health care delivery, as more Americans receive prescriptions and American
      psychiatrists provide less psychotherapy. Historically, communication between
      professionals treating the same patient has been an accepted principle of optimal
      care, but there has been only one formal assessment (Avena & Kalman, 2010a,b) of
      whether or not such communication actually takes place in the private sector.
      This article supplements the aforementioned survey of psychotherapists with a
      survey of psychiatrists. SUBJECTS AND METHODS: An eight-item survey was mailed to
      150 full-time private practice psychiatrists in Manhattan and New Jersey.
      Questionnaires were completed anonymously and returned by mail. Data was gathered
      about years of practice experience, how many patients were seen in the prior
      month, and how many patients were also in psychotherapy with another
      professional. Frequency of communication with psychotherapists on behalf of these
      patients and for patients in treatment for six months or longer was also
      assessed. Lastly, information was compiled on which professional more frequently
      initiated the communication when it did occur. RESULTS: Sixty-one psychiatrists,
      averaging 26.7 years in practice, returned surveys. For all respondents, the
      total number of medication-only patients seen in the last full month was 1903, of
      which 785 (41.25%) were in psychotherapy with another mental health professional.
      Respondents reported a total of 875 split-care patients in treatment for six
      months or longer, with no communication with the psychotherapist being reported
      on behalf of 24% of these individuals. Respondents indicated that they had
      initiated 68.4% of the most recent contacts with the other professional, and just
      10 of 55 (18.2%) responding psychiatrists reported quarterly communication with
      their split-care patients' psychotherapists for all shared patients. CONCLUSIONS:
      We found that split-care treatment is common but that adequate communication
      between professionals engaged in such treatment frequently does not take place.
      Corroborating the findings of the earlier survey, many questions remain about the
      need for guidelines regarding the conduct of split-treatment and about how best
      to determine the importance of communication between professionals engaged in
      this therapeutic arrangement.

PMID- 23006120
TI  - Dream analysis in the psychodynamic psychotherapy of borderline patients.
AB  - Despite Freud's dictum that dreams are the royal road to the unconscious, the use
      of dream analysis by therapists working with Borderline Personality Disorder and
      other severe psychiatric conditions has in the past two decades has fallen into a
      state of decline, if not outright neglect. The reasons why are not altogether
      clear, though some have said that the growing popularity of ego psychology and
      other movements in the domain of psychoanalysis have perhaps pushed dream
      analysis to one side. To me this marginalization seems unjustified. I hope to
      demonstrate in this article the enduring utility of dream analysis in working
      with the more severely disordered patients, with the aim of revivifying its
      application--and its efficacy--in our work with such patients.

PMID- 23006121
TI  - Objective measures of subjective experience: the use of therapist notes in
      process-outcome research.
AB  - Computerized linguistic measures of emotional engagement, and reflective and
      affective language, previously applied to session transcripts, were applied to
      notes of 14 treatments by candidates under supervision at the New York
      Psychoanalytic Society and Institute, covering the five decades from the 1950s to
      the 1990s. The findings indicate a strong relationship between candidates'
      subjective experience as represented unintentionally in the linguistic style of
      their case notes and the effectiveness of their clinical work. The treatments
      were evaluated for effectiveness by experienced clinicians using the Global
      Assessment of Functioning (GAF) and the Psychodynamic Functioning Scales of
      Hoglend and colleagues; a Composite Clinical Effectiveness (CCE) measure was
      constructed based on level and change in these measures. The Mean High Weighted
      Referential Activity Dictionary (MHW), a computerized measure of emotional
      engagement developed in the framework of Bucci's theory of multiple coding and
      the referential process, showed a positive correlation of .73 with CCE. The
      Hostility subcategory of the Negative Affect Dictionary (ANH) showed a negative
      correlation, -.48, with CCE. In a multiple regression analysis, these two
      variables accounted for over three-quarters of the variance in the CCE.
      Implications of the findings for process/outcome research and supervision and
      evaluation of trainees are discussed.

PMID- 23006123
TI  - Editorial comment for Cormio et al.

PMID- 23006124
TI  - Characterization of EssB, a protein required for secretion of ESAT-6 like
      proteins in Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus secretes EsxA and EsxB, two small polypeptides
      of the WXG100 family of proteins. Genetic analyses have shown that production and
      secretion of EsxA and EsxB require an intact ESAT-6 Secretion System (ESS), a
      cluster of genes that is conserved in many Firmicutes and encompasses esxA and
      esxB . Here, we characterize EssB, one of the proteins encoded by the ESS
      cluster. EssB is highly conserved in Gram-positive bacteria and belongs to the
      Cluster of Orthologous Groups of protein COG4499 with no known function. RESULTS:
      By generating an internal deletion in essB , we demonstrate that EssB is required
      for secretion of EsxA. We use a polyclonal antibody to identify EssB and show
      that the protein fractionates with the plasma membrane of S. aureus . Yet, when
      produced in Escherichia coli, EssB remains mostly soluble and the purified
      protein assembles into a highly organized oligomer that can be visualized by
      electron microscopy. Production of truncated EssB variants in wild-type S. aureus
      confers a dominant negative phenotype on EsxA secretion. CONCLUSIONS: The data
      presented here support the notion that EssB may oligomerize and interact with
      other membrane components to form the WXG100-specific translocon in S. aureus .

PMID- 23006125
TI  - Regulatory role of vitamin D in T-cell reactivity against myelin peptides in
      relapsing-remitting multiple sclerosis patients.
AB  - BACKGROUND: Low levels of plasma 25-hydroxyvitaminD (25(OH)D) are associated with
      a higher incidence of multiple sclerosis (MS) due to the immune suppressive
      properties of vitamin D.The aim of this study was to determine the correlation
      between plasma 25(OH)D concentrations and clinical and immunological variables in
      a cohort of multiple sclerosis patients. METHODS: Plasma 25(OH)D concentrations
      were evaluated in summer and winter in 15 primary progressive MS (PPMS) patients,
      40 relapsing- remitting MS (RRMS) patients and 40 controls (HC). Protocol
      variables included demographic and clinical data, radiological findings and
      immunological variables (oligoclonal bands, HLADR15 and T-lymphocyte
      proliferation to a definite mix of 7 myelin peptides). RESULTS: During the
      winter, plasma concentrations were significantly lower in RRMS patients compared
      to HC, whereas no differences were found in summer. No relationships were found
      between plasma 25(OH)D concentrations and clinical or radiological variables.
      RRMS patients with a positive T-cell proliferation to a mix of myelin peptides (n
      = 31) had lower 25(OH)D concentrations. CONCLUSIONS: 25(OH)D is an
      immunomodulatory molecule that might have a regulatory role in T-cell
      proliferation to myelin peptides in RRMS patients.

PMID- 23006126
TI  - Comparative effectiveness and safety of the novel oral anticoagulants: do the
      pivotal clinical trials point to a new paradigm?

PMID- 23006127
TI  - Ambulatory blood pressure monitoring for the early identification of hypertension
      in pregnancy.
AB  - Gestational hypertension and preeclampsia are major contributors to perinatal
      morbidity and mortality. The diagnosis of gestational hypertension still relies
      on conventional clinic blood pressure (BP) measurements and thresholds of
      >=140/90 mm Hg for systolic (SBP)/diastolic (DBP) BP. However, the correlation
      between BP level and target organ damage, cardiovascular disease risk, and long
      term prognosis is greater for ambulatory BP monitoring (ABPM) than clinic BP
      measurement. Accordingly, ABPM has been suggested as the logical approach to
      overcoming the low sensitivity and specificity of clinic BP measurements in
      pregnancy. With the use of ABPM, differing predictable BP patterns throughout
      gestation have been identified for clinically healthy and hypertensive pregnant
      women. In normotensive pregnancies, BP steadily decreases up to the middle of
      gestation and then increases up to the day of delivery. In contrast, women who
      develop gestational hypertension or preeclampsia show stable BP during the first
      half of pregnancy and a continuous linear BP increase thereafter until delivery.
      Epidemiologic studies have also consistently reported sex differences in the 24-h
      patterns of ambulatory BP and heart rate. Typically, men exhibit a lower heart
      rate and higher BP than women, the differences being larger for SBP than DBP.
      Additionally, as early as in the first trimester of gestation, statistically
      significant increased 24-h SBP and DBP means characterize women complicated with
      gestational hypertension or preeclampsia compared with women with uncomplicated
      pregnancies. However, the normally lower BP in nongravid women as compared with
      men, additional decrease in BP during the second trimester of gestation in
      normotensive but not in hypertensive pregnant women, and significant differences
      in the 24-h BP pattern between healthy and complicated pregnancies at all
      gestational ages have not been taken into consideration when establishing
      reference BP thresholds for the diagnosis of hypertension in pregnancy. Several
      studies reported that use of the 24-h BP mean is not a proper test for an
      individualized early diagnosis of hypertension in pregnancy defined on the basis
      of cuff BP measurements, thus concluding that from such an awkward approach ABPM
      is not useful in pregnancy. The 24-h BP pattern that characterizes healthy
      pregnant women at all gestational ages suggests the use for diagnosis of a time
      specified reference limit reflecting that mostly predictable BP variability. Once
      the time-varying threshold, given, for instance, by the upper limit of a
      tolerance interval, is available, the hyperbaric index (HBI), as a determinant of
      BP excess, can be calculated as the total area of any given subject's BP above
      the threshold. This tolerance-hyperbaric test, where diagnosis of gestational
      hypertension is based on the HBI calculated with reference to a time-specified
      tolerance limit, has been shown to provide high sensitivity and specificity for
      the early identification of subsequent hypertension in pregnancy, as well as a
      valuable approach for prediction of pregnancy outcome. ABPM during gestation,
      starting preferably at the time of the first obstetric check-up following
      positive confirmation of pregnancy, provides sensitive endpoints for use in early
      risk assessment and guide for establishing prophylactic or therapeutic
      intervention, and should thus be regarded as the required standard for the
      diagnosis of hypertension in pregnancy.

PMID- 23006128
TI  - Heterologous assembly of type IV pili by a type II secretion system reveals the
      role of minor pilins in assembly initiation.
AB  - In Gram-negative bacteria, type IV pilus assembly (T4PS) and type II secretion
      (T2SS) systems polymerize inner membrane proteins called major pilins or
      pseudopilins respectively, into thin filaments. Four minor pilins are required in
      both systems for efficient fibre assembly. Escherichia coli K-12 has a set of
      T4PS assembly genes that are silent under standard growth conditions. We studied
      the heterologous assembly of the E. coli type IV pilin PpdD by the Klebsiella
      oxytoca T2SS called the Pul system. PpdD pilus assembly in this context depended
      on the expression of the K. oxytoca minor pseudopilin genes pulHIJK or of the E.
      coli minor pilin genes ppdAB-ygdB-ppdC. The E. coli minor pilins restored
      assembly of the major pseudopilin PulG in a pulHIJK mutant, but not the secretion
      of the T2SS substrate pullulanase. Thus, minor pilins and minor pseudopilins are
      functionally interchangeable in initiating major pilin assembly, further
      extending the fundamental similarities between the two systems. The data suggest
      that, in both systems, minor pilins activate the assembly machinery through a
      common self-assembly mechanism. When produced together, PulG and PpdD assembled
      into distinct homopolymers, establishing major pilins as key determinants of
      pilus elongation and structure.

PMID- 23006129
TI  - Magnetic resonance imaging of pulp in normal and diseased equine cheek teeth.
AB  - A retrospective analysis of 619 upper and lower cheek teeth from 62 horses was
      performed. Based on clinical findings, as well as radiographic and magnetic
      resonance (MR) imaging findings, the teeth were classified into five groups.
      There were 20 teeth with abnormal MR imaging signals as well as clinical
      alterations and 599 healthy teeth. Using MR imaging, the appearance of pulp in
      diseased and disease-free teeth was compared, and the appearance of abnormal pulp
      was studied. Subsequently, the ability of MR imaging to diagnose pulpitis and
      pulp necrosis in teeth with normal external appearance was investigated. In
      horses with clinically verified dental disease, abnormal MR imaging findings were
      confirmed in the pulp of all affected teeth. An enlarged blurred pulp image with
      a lower signal intensity was observed only in clinically diseased teeth and was a
      reliable criterion for diagnosing dental disease on MR imaging. On the other
      hand, partial or complete absence of pulp in all MR imaging sequences was
      observed in both diseased and nondiseased teeth. These data demonstrate that pulp
      changes in equine cheek teeth can be evaluated using MR imaging.

PMID- 23006132
TI  - Pathological complete response and sphincter-sparing surgery after neoadjuvant
      radiochemotherapy with regional hyperthermia for locally advanced rectal cancer
      compared with radiochemotherapy alone.
AB  - PURPOSE: To evaluate the influence of regional hyperthermia on rates of complete
      pathological response (pCR) and sphincter-sparing surgery in the context of an up
      to-date radiochemotherapy protocol for locally advanced rectal cancer. METHODS:
      Between 2007 and 2010, 106 patients with locally advanced cancer of the middle
      and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n =
      61) or without (n = 45) regional hyperthermia. A retrospective comparison was
      performed between two groups: 45 patients received standard treatment consisting
      of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61
      patients received the same treatment in combination with regional hyperthermia
      (HRCT group). Target temperature was 40.5 degrees C for at least 60 min. Total
      mesorectal excision was performed routinely. RESULTS: pCR was seen in 6.7% of
      patients in the RCT group and 16.4% in the HRCT group. Patients who received at
      least four hyperthermia treatments (n = 40) achieved a significantly higher pCR
      rate (22.5%) than the remaining 66 patients (p = 0.043). Rates of sphincter
      sparing surgery were similar in both groups with 64% in the RCT group and 66% in
      HRCT. When considering only low-lying tumours located within 8 cm of the anal
      verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the
      HRCT group compared with 35% in the RCT group (p = 0.077). CONCLUSION: The
      combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead
      to an increased pCR rate in locally advanced rectal cancer. Patients with low
      lying tumours especially may benefit when additional downsizing allows sphincter
      preserving surgery.

PMID- 23006133
TI  - Quantifying size-dependent interactions between fluorescently labeled polystyrene
      nanoparticles and mammalian cells.
AB  - BACKGROUND: Nanoparticles (NPs) are currently used in a wide variety of fields
      such as technology, medicine and industry. Due to the novelty of these
      applications and to ensure their success, a precise characterization of the
      interactions between NPs and cells is essential. FINDINGS: The current study
      explores the uptake of polystyrene NPs by 1321N1 human astrocytoma and A549 human
      lung carcinoma cell lines. In this work we show for the first time a comparison
      of the uptake rates of fluorescently labeled carboxylated polystyrene (PS) NPs of
      different sizes (20, 40 and 100 nm) in two different cell types, keeping the
      number of NPs per unit volume constant for all sizes. We propose a reliable
      methodology to control the dose of fluorescently labeled NPs, by counting
      individual NPs using automated particle detection from 3D confocal microscopy
      images. The possibility of detecting individual NPs also allowed us to calculate
      the size of each nanoparticle and compare the fluorescence of single NPs across
      different sizes, thereby providing a robust platform for normalization of NP
      internalization experiments as measured by flow cytometry. CONCLUSIONS: Our
      findings show that 40 nm NPs are internalized faster than 20 nm or 100 nm
      particles in both cell lines studied, suggesting that there is a privileged size
      gap in which the internalization of NPs is higher.

PMID- 23006134
TI  - Interstage weight gain for patients with hypoplastic left heart syndrome
      undergoing the hybrid procedure.
AB  - BACKGROUND: Weight gain during the interstage (IS) period for hypoplastic left
      heart (HLHS) patients has been associated with improved outcomes. IS home
      monitoring has been shown to improve mortality. No data exist on IS weight gain
      and home monitoring effects on weight gain for HLHS patients undergoing the
      hybrid procedure. OBJECTIVE: Goal of this study was to describe the weight gain
      of patients with HLHS undergoing the hybrid procedure during the IS period, to
      determine if weight parameters were associated with mortality, and to determine
      if home monitoring improved weight gain. METHODS: Retrospective review was
      performed. Patients were included if they had the diagnosis of HLHS and underwent
      hybrid procedure. Baseline demographics, surgical dates, and all IS weights were
      recorded. RESULTS: Forty-four patients met inclusion criteria, 24 patients had IS
      monitoring. Time period evaluated was from April 2006 to June 2011. Mean birth
      weight of the total population was 3.13 +/- 0.61 kg, age at hybrid was 5.84 +/-
      4.10 days, weight z-score at hybrid discharge was -1.66 +/- 1.01, age at pre
      Stage II was 6.12 +/- 1.37 months, IS weight gain was 16.85 +/- 5.94 g/day, and
      weight z-score pre-Stage II was -2.25 +/- 1.28. Monitored patients had
      significantly higher weight z-score pre-Stage II (-1.67 +/- 0.98 vs. -2.82 +/-
      1.28) and lower change in weight z-score (-0.26 +/- 0.97 vs. -1.24 +/- 1.06).
      Eight patients died IS. There was a significant difference in weight gain per day
      in those that survived the IS period (17.87 +/- 4.75 g/day vs. 12.28 +/- 8.65
      g/day). There were no significant differences in weight characteristics in
      patients that survived the Stage II procedure (n = 28) vs. those that did not (n
      = 7). CONCLUSION: Home monitoring improved IS weight gain in patients undergoing
      the hybrid procedure. Decreased weight gain per day was associated with IS
      mortality.

PMID- 23006135
TI  - NXCL-4950, a novel composite applicable to peripheral skin, is capable of
      increasing skin temperature by enhancing capillary circulation.
AB  - BACKGROUND: Rapid skin warming and prompt correct medical treatment lead to
      dramatic improvement in patients with peripheral capillary-related damage, such
      as injuries, Raynaud disease and frostbite. AIM: To characterize a novel
      composite, NXCL-4950, for use in a cosmetic lotion. METHODS: The effects of NXCL
      4950 on enhancing skin blood flow, skin temperature warming, and expansion of
      peripheral blood vessels and scalp microvessels were investigated. RESULTS:
      Monitoring by laser Doppler perfusion imaging and thermal imaging showed that
      application of NXCL-4950 to the hands increased skin blood flow and temperature
      relative to the control (or placebo) group. For the 20 participants with a high
      Raynaud Condition Score, application of NXCL-4950 to the skin resulted in a mean
      increase of 215.53% in microvessel diameter and mean increase of 164.96% in the
      speed of blood flow. When NXCL-4950 was applied to the scalp, the microvessels
      around the hair roots were clearly visible after 20 min. CONCLUSION: NXCL-4950 is
      a potential candidate for enhancing peripheral skin temperature, and might be
      useful in the treatment of capillary-related disorders.

PMID- 23006136
TI  - Management of complete heart block during pregnancy.
AB  - A 22-year-old second gravida presented to the antenatal clinic at 28 weeks of
      gestation with frequent fainting attacks (2-3 episodes/day), palpitations and
      dyspnea (New York Heart Association Functional Classification II). Her pulse rate
      was 40 b.p.m. A 12-lead electrocardiogram and 24-h Holter revealed complete heart
      block. A transvenous permanent pacemaker (ventricular demand rate-responsive),
      paced at a rate of 60 pulses/min, was successfully implanted. A multidisciplinary
      approach was taken and the patient delivered a healthy baby boy of 2.8 kg at 38
      weeks. She remained asymptomatic and was discharged in good condition. Management
      varies from expectant management to temporary pacemaker insertion to permanent
      pacing during pregnancy. In a young patient with sinus bradycardia, the primary
      criterion for a pacemaker is the concurrent observation of a symptom (e.g.,
      syncope) with bradycardia (e.g., heart rate 35-40 b.p.m. or asystole for 3 s).
      Symptomatic pregnant women should always be counseled for a permanent pacemaker.

PMID- 23006137
TI  - Mechanistic insight into the formation of tetraarylazadipyrromethenes.
AB  - The tetraarylazadipyrromethene chromophore class has gained increasing attention
      in the past decade for a diverse set of scientific interests and applications.
      The most direct synthetic route available for their generation is heating of 4
      nitro-1,3-diarylbutan-1-ones with an ammonium source in an alcohol solvent.
      Despite the practical simplicity, the reaction pathway(s) for these conversions
      are lengthy and unclear. To gain insight into the steps involved, (15)N labeling
      experiments with MS and NMR analysis were utilized for conversion of 4-nitro-1,3
      diphenylbutan-1-one 1 into tetraphenylazadipyrromethene 2 with (15)NH(4)OAc. To
      permit examination of later stages of the reaction sequence to 2, the (15)N
      labeled potential intermediate 3,5-diphenyl-1H-pyrrol-2-amine 10 was synthesized.
      A study of the dimerization pathway utilizing (15)N-labeled 10 revealed an
      unprecedented nitrogen rearrangement in the final stages of the pathway involving
      a ring-opening/closing of a pyrrole ring. Utilizing (15)N labeling experiments we
      have shown that 2,4-diphenylpyrrole 8 can also react under the reaction
      conditions with 3,5-diphenyl-2H-pyrrol-2-imine 7 (from oxidation of  10) to
      produce 2. Overall in the conversion of 1 into 2, two related pathways are
      ongoing concurrently; the first involves a dimerization of 3,5-diphenyl-2H-pyrrol
      2-imine 7, and the other a reaction of 7 with 2,4-diphenylpyrrole 8.

PMID- 23006138
TI  - Why is the Liverpool care pathway used for some dying cancer patients and not
      others? Healthcare professionals' perspectives.
AB  - BACKGROUND: Despite evidence suggesting that the Liverpool Care Pathway for the
      Dying Patient is a structured and proficient means of supporting care delivery in
      the last hours or days of life, discrepancies in uptake are widespread. This
      exploratory study sought to understand why patients dying of cancer in oncology
      wards of one hospital trust were, or were not, supported by the LCP. A purposive
      qualitative case study design was used; each case represented a patient who had
      died and their most involved nurse and doctor. In-depth interviews explored both
      recollections of the 'case' and wider experiences of using the Pathway in end-of
      life care. Eleven healthcare professionals were interviewed about their
      involvement in the end-of-life care of six patients. For four of these patients
      care was supported by the LCP. FINDINGS: Although doctors and nurses reported
      they preferred to use the Pathway to ensure comfortable death, an important
      factor influencing their decisions was time of death. Access to timely senior
      review was regarded as an essential preliminary to placing patients on the
      Pathway but delayed access 'out of hours' was commonly experienced and tensions
      arose from balancing conflicting priorities. Consequently, the needs of dying
      patients sometimes failed to compete with those receiving curative treatment.
      CONCLUSIONS: This study suggests that greater attention should be focused on 'out
      of hours' care in hospitals to ensure regular senior review of all patients at
      risk of dying and to support front line staff to communicate effectively and make
      contingency plans focused on patients' best interests.

PMID- 23006139
TI  - Effect of nitrogen and waterlogging on denitrifier gene abundance, community
      structure and activity in the rhizosphere of wheat.
AB  - Microbial denitrification plays a key role in determining the availability of
      soil nitrogen (N) to plants. However, factors influencing the structure and
      function of denitrifier communities in the rhizosphere remain unclear.
      Waterlogging can result in root anoxia and increased denitrification, leading to
      significant N loss from soil and potential nitrous oxide (N(2)O) emissions. This
      study investigated denitrifier gene abundance, community structure and activity
      in the rhizosphere of wheat in response to anoxia and N limitation. Denitrifier
      community structure in the rhizosphere differed from that in bulk soil, and
      denitrifier gene copy numbers (nirS, nirK, nosZ) and potential denitrification
      activity were greater in the rhizosphere. Anoxia and N limitation, and in
      particular a combination of both, reduced the magnitude of this effect on gene
      abundance (in particular nirS) and activity, with N limitation having greater
      impact than waterlogging in rhizosphere soil, in contrast to bulk soil where the
      impact of waterlogging was greater. Increased N supply to anoxic plants improved
      plant health and increased rhizosphere soil pH, which resulted in enhanced
      reduction of N(2)O. Both anoxia and N limitation significantly influenced the
      structure and function of denitrifier communities in the rhizosphere, with
      reduced root-derived carbon postulated to play an important role.

PMID- 23006140
TI  - Continuity and discontinuity in perceptions of family relationships from
      adolescence to young adulthood.
AB  - The present 8-year longitudinal study examined how multiple aspects of family
      relationships change across the transition from adolescence (Mage  = 15 years) to
      young adulthood (Mage  = 22 years) among 821 individuals. Results showed that
      there was more discontinuity than continuity in family relationships across this
      transition. Whereas a normative decline was evident in all measured aspects of
      family relationships during adolescence, this decline persisted for only a few
      dimensions of family relationships during young adulthood. Other aspects of
      family relationships stabilized or rebounded. There was little variation in these
      trajectories as a function of ethnicity or gender, suggesting that these changes
      in family relationships are generally normative. Results suggest that the
      transition to adulthood is a period of significant transformation in family
      relationships.

PMID- 23006141
TI  - From despair to hope: a longitudinal study of illness perceptions and coping in a
      psycho-educational group intervention for women with breast cancer.
AB  - OBJECTIVES: This study examined the cross-sectional and longitudinal
      relationships of illness perceptions, coping, and distress in women with breast
      cancer. Illness perceptions and coping at baseline and changes in these variables
      over time served as possible predictors of distress at two follow-up points.
      DESIGN AND METHODS: Fifty-seven women with breast cancer who participated in a
      psychosocial aftercare programme completed a questionnaire before the start of
      the intervention, directly after the end of the intervention, and 1 year after
      the start of the intervention. Study variables were assessed with the Illness
      Perception Questionnaire-Revised (illness perceptions), the COPE (coping), and
      the Hopkins Symptom Check List (distress). RESULTS: Results showed that 43% of
      variance in distress at baseline was explained by participants' illness
      perceptions. Cyclical timeline perceptions were the strongest predictor of
      distress at baseline. Longitudinal data revealed that after the end of the
      intervention, the intensity of general distress and breast cancer-related
      emotions had decreased significantly. Partial correlations showed that baseline
      illness perceptions were unrelated to distress at follow-up. However, changes in
      illness perceptions (perceptions about the cyclical and chronic timeline and
      symptoms associated with breast cancer) showed significant associations with
      distress at both follow-up assessments. Associations of follow-up distress with
      coping styles were less consistent. CONCLUSIONS: Our results suggest that changes
      in illness perceptions are related to an improvement or worsening of patients'
      emotional well-being over time. These findings hold promise for the development
      of interventions that specifically target patients' representations of their
      illness.

PMID- 23006142
TI  - Nutrition for adventure racing.
AB  - Adventure racing requires competitors to perform various disciplines ranging
      from, but not limited to, mountain biking, running, kayaking, climbing,
      mountaineering, flat- and white-water boating and orienteering over a rugged,
      often remote and wilderness terrain. Races can vary from 6 hours to expedition
      length events that can last up to 10-consecutive days or more. The purpose of
      this article is to provide evidence-based nutritional recommendations for
      adventure racing competitors. Energy expenditures of 365-750 kcal/hour have been
      reported with total energy expenditures of 18 000-80 000 kcal required to
      complete adventure races, and large negative energy balances during competitions
      have been reported. Nutrition, therefore, plays a major role in the successful
      completion of such ultra-endurance events. Conducting research in these events is
      challenging and the limited studies investigating dietary surveys and nutritional
      status of adventure racers indicate that competitors do not meet nutrition
      recommendations for ultra-endurance exercise. Carbohydrate intakes of 7-12 g/kg
      are needed during periods of prolonged training to meet requirements and
      replenish glycogen stores. Protein intakes of 1.4-1.7 g/kg are recommended to
      build and repair tissue. Adequate replacement of fluid and electrolytes are
      crucial, particularly during extreme temperatures; however, sweat rates can vary
      greatly between competitors. There is considerable evidence to support the use of
      sports drinks, gels and bars, as they are a convenient and portable source of
      carbohydrate that can be consumed during exercise, in training and in
      competition. Similarly, protein and amino acid supplements can be useful to help
      meet periods of increased protein requirements. Caffeine can be used as an
      ergogenic aid to help competitors stay awake during prolonged periods, enhance
      glycogen resynthesis and enhance endurance performance.

PMID- 23006143
TI  - Conservative management of midportion Achilles tendinopathy: a mixed methods
      study, integrating systematic review and clinical reasoning.
AB  - BACKGROUND: Clinicians manage midportion Achilles tendinopathy (AT) using complex
      clinical reasoning underpinned by a rapidly developing evidence base. OBJECTIVES:
      The objectives of the study were to develop an inclusive, accessible review of
      the literature in combination with an account of expert therapists' related
      clinical reasoning to guide clinical practice and future research. METHODS:
      Searches of the electronic databases, PubMed, ISI Web of Science, PEDro, CINAHL,
      EMBASE, and Google Scholar were conducted for all papers published from inception
      to November 2011. Reference lists and citing articles were searched for further
      relevant articles. Inclusion required studies to evaluate the effectiveness of
      any conservative intervention for midportion AT. Exclusion criteria included in
      vitro, animal and cadaver studies and tendinopathies in other locations (e.g.
      patella, supraspinatus). From a total of 3497 identified in the initial search,
      47 studies fulfilled the inclusion criteria. Studies were scored according to the
      PEDro scale, with a score of >= 8/10 considered of excellent quality, 5-7/10
      good, and <= 4/10 poor. The strength of evidence supporting each treatment
      modality was then rated as 'strong', 'moderate', 'limited', 'conflicting' or 'no
      evidence' according to the number and quality of articles supporting that
      modality. Additionally, semi-structured interviews were conducted with
      physiotherapists to explore clinical reasoning related to the use of various
      interventions with and without an evidence base, and their perceptions of
      available evidence. RESULTS: Evidence was strong for eccentric loading exercises
      and extracorporeal shockwave therapy; moderate for splinting/bracing, active
      rest, low-level laser therapy and concentric exercises (i.e. inferior to
      eccentric exercise). In-shoe foot orthoses and therapeutic ultrasound had limited
      evidence. There was conflicting evidence for topical glycerin trinitrate. Taping
      techniques and soft-tissue mobilization were not yet examined but featured in
      case studies and in the interview data. Framework analysis of interview
      transcripts yielded multiple themes relating to physiotherapists' clinical
      reasoning and perceptions of the evidence, including the difficulty in causing
      pain while treating the condition and the need to vary research protocols for
      specific client groups--such as those with the metabolic syndrome as a likely
      etiological factor. Physiotherapists were commonly applying the modality with the
      strongest evidence base, eccentric loading exercises. Barriers to research being
      translated into practice identified included the lack of consistency of outcome
      measures, excessive stringency of some authoritative reviews and difficulty in
      accessing primary research reports. The broad inclusion criteria meant some lower
      quality studies were included in this review. However, this was deliberate to
      ensure that all available research evidence for the management of midportion AT,
      and all studies were evaluated using the PEDro scale to compensate for the lack
      of stringent inclusion criteria. CONCLUSION: Graded evidence combined with
      qualitative analysis of clinical reasoning produced a novel and clinically
      applicable guide to conservative management of midportion AT. This guide will be
      useful to novice clinicians learning how to manage this treatment-resistant
      condition and to expert clinicians reviewing their evidence-based practice and
      developing their clinical reasoning. Important areas requiring future research
      were identified including the effectiveness of orthoses, the effectiveness of
      manual therapy, etiological factors, optimal application of loading related to
      stage of presentation and how to optimize protocols for different types of
      patients such as the older patient with the metabolic syndrome as opposed to the
      athletically active.

PMID- 23006144
TI  - Expression of IL-20 in synovium and lesional skin of patients with psoriatic
      arthritis: differential response to alefacept treatment.
AB  - INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory joint disease
      associated with psoriasis. Alefacept (a lymphocyte function-associated antigen
      (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T
      cell activation) has been shown to result in improvement in psoriasis but has
      limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory
      cytokine involved in the pathogenesis of psoriasis. The effects of alefacept
      treatment on IL-20 expression in the synovium of patients with psoriasis and PsA
      are currently unknown. METHODS: Eleven patients with active PsA and chronic
      plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an
      open-label study. Skin biopsies were taken before and after 1 and 6 weeks,
      whereas synovial biopsies were obtained before and 4 and 12 weeks after
      treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n =
      10) were used as disease controls. Immunohistochemical analysis was performed to
      detect IL-20 expression, and stained synovial tissue sections were evaluated with
      digital image analysis. Double staining was performed with IL-20 and CD68
      (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to
      determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression
      in skin sections (n = 6) was analyzed semiquantitatively. RESULTS: IL-20 was
      abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA
      synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression
      correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA
      patients decreased significantly (P = 0.04) 6 weeks after treatment and
      correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20
      expression in PsA synovium was not affected by alefacept. CONCLUSIONS:
      Conceivably, the relatively limited effectiveness of alefacept in PsA patients
      (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in
      part by persistent FLS-derived IL-20 expression.

PMID- 23006145
TI  - Developing a guideline for clinical trial protocol content: Delphi consensus
      survey.
AB  - BACKGROUND: Recent evidence has highlighted deficiencies in clinical trial
      protocols, having implications for many groups. Existing guidelines for
      randomized clinical trial (RCT) protocol content vary substantially and most do
      not describe systematic methodology for their development. As one of three
      prespecified steps for the systematic development of a guideline for trial
      protocol content, the objective of this study was to conduct a three-round Delphi
      consensus survey to develop and refine minimum content for RCT protocols.
      METHODS: Panellists were identified using a multistep iterative approach, met
      prespecified minimum criteria and represented key stakeholders who develop or use
      clinical trial protocols. They were asked to rate concepts for importance in a
      minimum set of items for RCT protocols. The main outcome measures were degree of
      importance (scale of 1 to 10; higher scores indicating higher importance) and
      level of consensus for items. Results were presented as medians, interquartile
      ranges, counts and percentages. RESULTS: Ninety-six expert panellists
      participated in the Delphi consensus survey including trial investigators,
      methodologists, research ethics board members, funders, industry, regulators and
      journal editors. Response rates were between 88 and 93% per round. Overall,
      panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th
      percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and
      12 of low importance (median less than or equal to 5) for minimum trial protocol
      content. General and item-specific comments and subgroup results provided
      valuable insight for further discussions. CONCLUSIONS: This Delphi process
      achieved consensus from a large panel of experts from diverse stakeholder groups
      on essential content for RCT protocols. It also highlights areas of divergence.
      These results, complemented by other empirical research and consensus meetings,
      are helping guide the development of a guideline for protocol content.

PMID- 23006146
TI  - On the potential of metformin to prevent preterm delivery in women with
      polycystic ovary syndrome - an epi-analysis.
AB  - Our aim was to re-evaluate whether metformin may reduce late miscarriage/preterm
      delivery, pre-eclampsia and gestational diabetes in women with polycystic ovary
      syndrome (PCOS). We performed an epi-analysis of two randomized controlled
      trials. The participants were 313 women aged 18-42 years with PCOS who had
      singleton pregnancies. They were randomized to metformin or placebo treatment
      from first trimester until delivery. We analysed the prevalence of late
      miscarriage/preterm delivery, pre-eclampsia and gestational diabetes according to
      both the intention-to-treat principle and per protocol analysis. The metformin
      treated patients had less late miscarriage/preterm delivery; five (3%) vs. 18
      (11%) in the placebo group (p < 0.01). There was no difference in the prevalence
      of gestational diabetes and pre-eclampsia between the metformin and the placebo
      group. In this epi-analysis, metformin treatment during pregnancy seems to reduce
      early delivery in women with PCOS. We believe that further randomized studies
      should be performed before firm conclusions can be drawn.

PMID- 23006148
TI  - Decoherence window and electron-nuclear cross relaxation in the molecular magnet
      V15.
AB  - Rabi oscillations in the V(15) single molecule magnet embedded in the surfactant
      (CH(3))(2)[CH(3)(CH(2))(16)CH(2)](2)N(+) have been studied at different microwave
      powers. An intense damping peak is observed when the Rabi frequency Omega(R)
      falls in the vicinity of the Larmor frequency of protons omega(N). The
      experiments are interpreted by a model showing that the damping (or Rabi) time
      tau(R) is directly associated with decoherence caused by electron-nuclear cross
      relaxation in the rotating reference frame. This decoherence induces energy
      dissipation in the range omega(N) - sigma(e) < Omega(R) < omega(N), where
      sigma(e) is the mean superhyperfine field induced by protons at V(15). Weaker
      decoherence without dissipation takes place outside this window. Specific
      estimations suggest that this rapid cross relaxation in a resonant microwave
      field, observed for the first time in V(15), should also take place, e.g., in
      Fe(8) and Mn(12).

PMID- 23006147
TI  - Sesquiterpenoids from the mangrove-derived endophytic fungus Diaporthe sp.
AB  - A new sesquiterpenoid, diaporol A (1), possessing a unique tricyclic lactone
      framework, eight new drimane sesquiterpenoids, diaporols B-I (2-9), and the known
      compounds 10 and 11 were isolated from a culture of the mangrove-derived
      endophyte Diaporthe sp. The absolute configurations of 1-5 were determined by low
      temperature (100 K) single-crystal X-ray diffraction with Cu Kalpha radiation.
      The compounds were evaluated for cytotoxic activity; however, no compound showed
      significant cytotoxicity against the tested cell lines at a concentration of 20
      MUM.

PMID- 23006149
TI  - Order parameter for symmetry-protected phases in one dimension.
AB  - We introduce an order parameter for symmetry-protected phases in one dimension
      which allows us to directly identify those phases. The order parameter consists
      of stringlike operators and swaps, but differs from conventional string order
      operators in that it only depends on the symmetry but not on the state. We verify
      our framework through numerical simulations for the SO(3) invariant spin-1
      bilinear-biquadratic model which exhibits a dimerized and a Haldane phase, and
      find that the order parameter not only works very well for the dimerized and the
      Haldane phase, but it also returns a distinct signature for gapless phases.
      Finally, we discuss possible ways to measure the order parameter in experiments
      with cold atoms.

PMID- 23006150
TI  - Dynamic spin response of a strongly interacting Fermi gas.
AB  - We present an experimental investigation of the dynamic spin response of a
      strongly interacting Fermi gas using Bragg spectroscopy. By varying the detuning
      of the Bragg lasers, we show that it is possible to measure the response in the
      spin and density channels separately. At low Bragg energies, the spin response is
      suppressed due to pairing, whereas the density response is enhanced. These
      experiments yield the first independent measurements of the spin-parallel and
      spin-antiparallel dynamic and static structure factors, which provide insight
      into the different features of density and spin response functions. At high
      momentum the spin-antiparallel dynamic structure factor displays a universal high
      frequency tail, proportional to omega(-5/2), where homega is the probe energy.

PMID- 23006151
TI  - Generalized monogamy of contextual inequalities from the no-disturbance
      principle.
AB  - In this Letter, we demonstrate that the property of monogamy of Bell violations
      seen for no-signaling correlations in composite systems can be generalized to the
      monogamy of contextuality in single systems obeying the Gleason property of no
      disturbance. We show how one can construct monogamies for contextual inequalities
      by using the graph-theoretic technique of vertex decomposition of a graph
      representing a set of measurements into subgraphs of suitable independence
      numbers that themselves admit a joint probability distribution. After
      establishing that all the subgraphs that are chordal graphs admit a joint
      probability distribution, we formulate a precise graph-theoretic condition that
      gives rise to the monogamy of contextuality. We also show how such monogamies
      arise within quantum theory for a single four-dimensional system and interpret
      violation of these relations in terms of a violation of causality. These
      monogamies can be tested with current experimental techniques.

PMID- 23006152
TI  - Quantum speedup by quantum annealing.
AB  - We study the glued-trees problem from A. M. Childs, R. Cleve, E. Deotto, E.
      Farhi, S. Gutmann, and D. Spielman, in Proceedings of the 35th Annual ACM
      Symposium on Theory of Computing (ACM, San Diego, CA, 2003), p. 59. in the
      adiabatic model of quantum computing and provide an annealing schedule to solve
      an oracular problem exponentially faster than classically possible. The
      Hamiltonians involved in the quantum annealing do not suffer from the so-called
      sign problem. Unlike the typical scenario, our schedule is efficient even though
      the minimum energy gap of the Hamiltonians is exponentially small in the problem
      size. We discuss generalizations based on initial-state randomization to avoid
      some slowdowns in adiabatic quantum computing due to small gaps.

PMID- 23006153
TI  - Number-theoretic nature of communication in quantum spin systems.
AB  - The last decade has witnessed substantial interest in protocols for transferring
      information on networks of quantum mechanical objects. A variety of control
      methods and network topologies have been proposed, on the basis that transfer
      with perfect fidelity-i.e., deterministic and without information loss-is
      impossible through unmodulated spin chains with more than a few particles.
      Solving the original problem formulated by Bose [Phys. Rev. Lett. 91, 207901
      (2003)], we determine the exact number of qubits in unmodulated chains (with an
      XY Hamiltonian) that permit transfer with a fidelity arbitrarily close to 1, a
      phenomenon called pretty good state transfer. We prove that this happens if and
      only if the number of nodes is n = p - 1, 2p - 1, where p is a prime, or n = 2(m)
      - 1. The result highlights the potential of quantum spin system dynamics for
      reinterpreting questions about the arithmetic structure of integers and, in this
      case, primality.

PMID- 23006154
TI  - Are general quantum correlations monogamous?
AB  - Quantum entanglement and quantum nonlocality are known to exhibit monogamy; that
      is, they obey strong constraints on how they can be distributed among
      multipartite systems. Quantum correlations that comprise and go beyond
      entanglement are quantified by, e.g., quantum discord. It was observed recently
      that for some states quantum discord is not monogamous. We prove, in general,
      that any measure of correlations that is monogamous for all states and satisfies
      reasonable basic properties must vanish for all separable states: only
      entanglement measures can be strictly monogamous. Monogamy of other than
      entanglement measures can still be satisfied for special, restricted cases: we
      prove that the geometric measure of discord satisfies the monogamy inequality on
      all pure states of three qubits.

PMID- 23006155
TI  - Efficient polar coding of quantum information.
AB  - Polar coding, introduced 2008 by Arikan, is the first (very) efficiently
      encodable and decodable coding scheme whose information transmission rate
      provably achieves the Shannon bound for classical discrete memoryless channels in
      the asymptotic limit of large block sizes. Here, we study the use of polar codes
      for the transmission of quantum information. Focusing on the case of qubit Pauli
      channels and qubit erasure channels, we use classical polar codes to construct a
      coding scheme that asymptotically achieves a net transmission rate equal to the
      coherent information using efficient encoding and decoding operations and code
      construction. Our codes generally require preshared entanglement between sender
      and receiver, but for channels with a sufficiently low noise level we demonstrate
      that the rate of preshared entanglement required is zero.

PMID- 23006156
TI  - Quantum algorithm for data fitting.
AB  - We provide a new quantum algorithm that efficiently determines the quality of a
      least-squares fit over an exponentially large data set by building upon an
      algorithm for solving systems of linear equations efficiently [Harrow et al.,
      Phys. Rev. Lett. 103, 150502 (2009)]. In many cases, our algorithm can also
      efficiently find a concise function that approximates the data to be fitted and
      bound the approximation error. In cases where the input data are pure quantum
      states, the algorithm can be used to provide an efficient parametric estimation
      of the quantum state and therefore can be applied as an alternative to full
      quantum-state tomography given a fault tolerant quantum computer.

PMID- 23006157
TI  - Heralded state preparation in a superconducting qubit.
AB  - We demonstrate high-fidelity, quantum nondemolition, single-shot readout of a
      superconducting flux qubit in which the pointer state distributions can be
      resolved to below one part in 1000. In the weak excitation regime, continuous
      measurement permits the use of heralding to ensure initialization to a fiducial
      state, such as the ground state. This procedure boosts readout fidelity to 93.9%
      by suppressing errors due to spurious thermal population. Furthermore, heralding
      potentially enables a simple, fast qubit reset protocol without changing the
      system parameters to induce Purcell relaxation.

PMID- 23006158
TI  - Initialization by measurement of a superconducting quantum bit circuit.
AB  - We demonstrate initialization by joint measurement of two transmon qubits in 3D
      circuit quantum electrodynamics. Homodyne detection of cavity transmission is
      enhanced by Josephson parametric amplification to discriminate the two-qubit
      ground state from single-qubit excitations nondestructively and with 98.1%
      fidelity. Measurement and postselection of a steady-state mixture with 4.7%
      residual excitation per qubit achieve 98.8% fidelity to the ground state, thus
      outperforming passive initialization.

PMID- 23006159
TI  - Direct transition from quantum escape to a phase diffusion regime in YBaCuO
      biepitaxial Josephson junctions.
AB  - Dissipation encodes the interaction of a quantum system with the environment and
      regulates the activation regimes of a Brownian particle. We have engineered grain
      boundary biepitaxial YBaCuO junctions to drive a direct transition from a quantum
      activated running state to a phase diffusion regime. The crossover to the quantum
      regime is tuned by the magnetic field and dissipation is described by a fully
      consistent set of junction parameters. To unravel phase dynamics in moderately
      damped systems is of general interest for advances in the comprehension of
      retrapping phenomena and in view of quantum hybrid technology.

PMID- 23006160
TI  - Mean-field theory for the inverse Ising problem at low temperatures.
AB  - The large amounts of data from molecular biology and neuroscience have lead to a
      renewed interest in the inverse Ising problem: how to reconstruct parameters of
      the Ising model (couplings between spins and external fields) from a number of
      spin configurations sampled from the Boltzmann measure. To invert the
      relationship between model parameters and observables (magnetizations and
      correlations), mean-field approximations are often used, allowing the
      determination of model parameters from data. However, all known mean-field
      methods fail at low temperatures with the emergence of multiple thermodynamic
      states. Here, we show how clustering spin configurations can approximate these
      thermodynamic states and how mean-field methods applied to thermodynamic states
      allow an efficient reconstruction of Ising models also at low temperatures.

PMID- 23006161
TI  - Second-order gravitational self-force.
AB  - Using a rigorous method of matched asymptotic expansions, I derive the equation
      of motion of a small, compact body in an external vacuum spacetime through second
      order in the body's mass (neglecting effects of internal structure). The motion
      is found to be geodesic in a certain locally defined regular geometry satisfying
      Einstein's equation at second order. I outline a method of numerically obtaining
      both the metric of that regular geometry and the complete second-order metric
      perturbation produced by the body.

PMID- 23006162
TI  - Testing gravity with the stacked phase space around galaxy clusters.
AB  - In general relativity, the average velocity field of dark matter around galaxy
      clusters is uniquely determined by the mass profile. The latter can be measured
      through weak lensing. We propose a new method of measuring the velocity field
      (phase space density) by stacking redshifts of surrounding galaxies from a
      spectroscopic sample. In combination with lensing, this yields a direct test of
      gravity on scales of 1-30 Mpc. Using N-body simulations, we show that this method
      can improve upon current constraints on f(R) and Dvali-Gabadadze-Porrati model
      parameters by several orders of magnitude when applied to upcoming imaging and
      redshift surveys.

PMID- 23006163
TI  - Asymmetric Higgsino dark matter.
AB  - In the supersymmetric framework, prior to the electroweak phase transition, the
      existence of a baryon asymmetry implies the existence of a Higgsino asymmetry. We
      investigate whether the Higgsino could be a viable asymmetric dark matter
      candidate. We find that this is indeed possible. Thus, supersymmetry can provide
      the observed dark matter abundance and, furthermore, relate it with the baryon
      asymmetry, in which case the puzzle of why the baryonic and dark matter mass
      densities are similar would be explained. To accomplish this task, two conditions
      are required. First, the gauginos, squarks, and sleptons must all be very heavy,
      such that the only electroweak-scale superpartners are the Higgsinos. With this
      spectrum, supersymmetry does not solve the fine-tuning problem. Second, the
      temperature of the electroweak phase transition must be low, in the (1-10) GeV
      range. This condition requires an extension of the minimal supersymmetric
      standard model.

PMID- 23006164
TI  - Isotropic blackbody cosmic microwave background radiation as evidence for a
      homogeneous universe.
AB  - The question of whether the Universe is spatially homogeneous and isotropic on
      the largest scales is of fundamental importance to cosmology but has not yet been
      answered decisively. Surprisingly, neither an isotropic primary cosmic microwave
      background (CMB) nor combined observations of luminosity distances and galaxy
      number counts are sufficient to establish such a result. The inclusion of the
      Sunyaev-Zel'dovich effect in CMB observations, however, dramatically improves
      this situation. We show that even a solitary observer who sees an isotropic
      blackbody CMB can conclude that the Universe is homogeneous and isotropic in
      their causal past when the Sunyaev-Zel'dovich effect is present. Critically,
      however, the CMB must either be viewed for an extended period of time, or CMB
      photons that have scattered more than once must be detected. This result provides
      a theoretical underpinning for testing the cosmological principle with
      observations of the CMB alone.

PMID- 23006165
TI  - Proposal for an observational test of the Vainshtein mechanism.
AB  - Modified gravity theories capable of genuine self-acceleration typically invoke a
      Galileon scalar which mediates a long-range force but is screened by the
      Vainshtein mechanism on small scales. In such theories, nonrelativistic stars
      carry the full scalar charge (proportional to their mass), while black holes
      carry none. Thus, for a galaxy free falling in some external gravitational field,
      its central massive black hole is expected to lag behind the stars. To look for
      this effect, and to distinguish it from other astrophysical effects, one can
      correlate the gravitational pull from the surrounding structure with the offset
      between the stellar center and the black hole. The expected offset depends on the
      central density of the galaxy and ranges up to ~0.1 kpc for small galaxies. The
      observed offset in M87 cannot be explained by this effect unless the scalar force
      is significantly stronger than gravity. We also discuss the systematic offset of
      compact objects from the galactic plane as another possible signature.

PMID- 23006167
TI  - Spin multiplicity and symmetry breaking in vanadium-benzene complexes.
AB  - We present accurate quantum Monte Carlo (QMC) calculations which enabled us to
      determine the structure, spin multiplicity, ionization energy, dissociation
      energy, and spin-dependent electronic gaps of the vanadium-benzene system. From
      total and ionization energy we deduce a high-spin state with vastly different
      energy gaps for the two spin channels. For this purpose we have used a multistage
      combination of techniques with consecutive elimination of systematic biases
      except for the fixed-node approximation in QMC calculations. Our results
      significantly differ from the established picture based on previous less accurate
      calculations and point out the importance of high-level many-body methods for
      predictive calculations of similar transition metal-based organometallic systems.

PMID- 23006166
TI  - Medium-mass nuclei with normal-ordered chiral NN+3N interactions.
AB  - We study the use of truncated normal-ordered three-nucleon interactions in
      nuclear structure calculations starting from chiral two- plus three-nucleon
      Hamiltonians evolved consistently with the similarity renormalization group. We
      present three key developments: (i) a rigorous benchmark of the normal-ordering
      approximation in the importance-truncated no-core shell model for (4)He, (16)O,
      and (40)Ca; (ii) a direct comparison of the importance-truncated no-core shell
      model results with coupled-cluster calculations at the singles and doubles level
      for (16)O; and (iii) first applications of similarity renormalization group
      evolved chiral NN+3N Hamiltonians in coupled-cluster calculations for medium-mass
      nuclei (16,24)O and (40,48)Ca. We show that the normal-ordered two-body
      approximation works very well beyond the lightest isotopes and opens a path for
      studies of medium-mass and heavy nuclei with chiral two- plus three-nucleon
      interactions. At the same time we highlight the predictive power of chiral
      Hamiltonians.

PMID- 23006168
TI  - Cooperative excitation and many-body interactions in a cold Rydberg gas.
AB  - The dipole blockade of Rydberg excitations is a hallmark of the strong
      interactions between atoms in these high-lying quantum states [M. Saffman, T. G.
      Walker, and K. Molmer, Rev. Mod. Phys. 82, 2313 (2010); D. Comparat and P.
      Pillet, J. Opt. Soc. Am. B 27, A208 (2010)]. One of the consequences of the
      dipole blockade is the suppression of fluctuations in the counting statistics of
      Rydberg excitations, of which some evidence has been found in previous
      experiments. Here we present experimental results on the dynamics and the
      counting statistics of Rydberg excitations of ultracold rubidium atoms both on
      and off resonance, which exhibit sub- and super-Poissonian counting statistics,
      respectively. We compare our results with numerical simulations using a novel
      theoretical model based on Dicke states of Rydberg atoms including dipole-dipole
      interactions, finding good agreement between experiment and theory.

PMID- 23006169
TI  - Structural transitions of ion strings in quantum potentials.
AB  - We analyze the stability and dynamics of an ion chain confined inside a high
      finesse optical resonator. When the dipolar transition of the ions strongly
      couples to one cavity mode, the mechanical effects of light modify the chain
      properties close to a structural transition. We focus on the linear chain close
      to the zigzag instability and show that linear and zigzag arrays are bistable for
      certain strengths of the laser pumping the cavity. For these regimes the chain is
      cooled into one of the configurations by cavity-enhanced photon scattering. The
      excitations of these structures mix photonic and vibrational fluctuations, which
      can be entangled at steady state. These features are signaled by Fano-like
      resonances in the spectrum of light at the cavity output.

PMID- 23006170
TI  - Classical simulations including electron correlations for sequential double
      ionization.
AB  - With a classical ensemble model that includes electron correlations during the
      whole ionization process, we investigate strong-field sequential double
      ionization of Ar by elliptically polarized pulses at the quantitative level. The
      experimentally observed intensity-dependent three-band or four-band structures in
      the ion momentum distributions are well reproduced with this classical model.
      More importantly, the experimentally measured ionization time of the second
      electrons by A. N. Pfeiffer et al. [Nature Phys. 7, 428 (2011)], which cannot be
      predicted by the standard independent-electron model, is quantitatively
      reproduced by this fully classical correlated model. The success of our work
      encourages classical descriptions and interpretations of the complex
      multielectron effects in strong-field ionization where nonperturbative quantum
      approaches are currently not feasible.

PMID- 23006171
TI  - Phase transition of light in cavity QED lattices.
AB  - Systems of strongly interacting atoms and photons, which can be realized wiring
      up individual cavity QED systems into lattices, are perceived as a new platform
      for quantum simulation. While sharing important properties with other systems of
      interacting quantum particles, here we argue that the nature of light-matter
      interaction gives rise to unique features with no analogs in condensed matter or
      atomic physics setups. By discussing the physics of a lattice model of
      delocalized photons coupled locally with two-level systems through the elementary
      light-matter interaction described by the Rabi model, we argue that the inclusion
      of counterrotating terms, so far neglected, is crucial to stabilize finite
      density quantum phases of correlated photons out of the vacuum, with no need for
      an artificially engineered chemical potential. We show that the competition
      between photon delocalization and Rabi nonlinearity drives the system across a
      novel Z(2) parity symmetry-breaking quantum criticality between two gapped phases
      that share similarities with the Dicke transition of quantum optics and the Ising
      critical point of quantum magnetism. We discuss the phase diagram as well as the
      low-energy excitation spectrum and present analytic estimates for critical
      quantities.

PMID- 23006172
TI  - Adaptive detection of arbitrarily shaped ultrashort quantum light states.
AB  - A quantum state of light is the excitation of a particular spatiotemporal mode of
      the electromagnetic field. A precise control of the mode structure is therefore
      essential for processing, detecting, and using photonic states in novel quantum
      technologies. Here we demonstrate an adaptive scheme, combining techniques from
      the fields of ultrafast coherent control and quantum optics, for probing the
      arbitrary complex spectrotemporal profile of an ultrashort quantum light pulse.
      The ability to access the modal structure of a quantum light state could boost
      the capacity of current quantum information protocols.

PMID- 23006173
TI  - Photonic signal processing on electronic scales: electro-optical field-effect
      nanoplasmonic modulator.
AB  - We develop a highly efficient approach for the modulation of photonic signals at
      the nanoscale, combining an ultrasubwavelength plasmonic guiding scheme with a
      robust electroabsorption effect in degenerate semiconductors. We numerically
      demonstrate an active electro-optical field-effect nanoplasmonic modulator with a
      revolutionary size of just 25 * 30 * 100 nm(3), providing signal extinction
      ratios as high as 2 at switching voltages of only 1 V. The design is compatible
      with complementary metal-oxide-semiconductor (CMOS) technology and allows low
      loss insertion in standard plasmonic and Si-photonic circuitry.

PMID- 23006174
TI  - dc electric invisibility cloak.
AB  - We present the first experimental demonstration of a dc electric cloak for steady
      current fields. Using the analogy between electrically conducting materials and
      resistor networks, a dc invisibility cloak is designed, fabricated, and tested
      using the circuit theory. We show that the dc cloak can guide electric currents
      around the cloaked region smoothly and keep perturbations only inside the cloak.
      Outside the cloak, the current lines return to their original directions as if
      nothing happens. The measurement data agree exceptionally well with the
      theoretical prediction and simulation result, with nearly perfect cloaking
      performance. The proposed method can be directly used to realize other dc
      electric devices with anisotropic conductivities designed by the transformation
      optics. Manipulation of steady currents with the control of anisotropic
      conductivities has a lot of potential applications, such as electric impedance
      tomography, graphene, natural resource exploration, and military camouflage.

PMID- 23006175
TI  - Optically driven quantum dots as source of coherent cavity phonons: a proposal
      for a phonon laser scheme.
AB  - We present a microscopically based scheme for the generation of coherent cavity
      phonons (phonon laser) by an optically driven semiconductor quantum dot coupled
      to a THz acoustic nanocavity. External laser pump light on an anti-Stokes
      resonance creates an effective Lambda system within a two-level dot that leads to
      coherent phonon statistics. We use an inductive equation of motion method to
      estimate a realistic parameter range for an experimental realization of such
      phonon lasers. This scheme for the creation of nonequilibrium phonons is robust
      with respect to radiative and phononic damping and only requires optical Rabi
      frequencies of the order of the electron-phonon coupling strength.

PMID- 23006176
TI  - Stamping and wrinkling of elastic plates.
AB  - We study the peculiar wrinkling pattern of an elastic plate stamped into a
      spherical mold. We show that the wavelength of the wrinkles decreases with their
      amplitude, but reaches a minimum when the amplitude is of the order of the
      thickness of the plate. The force required for compressing the wrinkled plate
      presents a maximum independent of the thickness. A model is derived and verified
      experimentally for a simple one-dimensional case. This model is extended to the
      initial situation through an effective Young modulus representing the mechanical
      behavior of the wrinkled state. The theoretical predictions are shown to be in
      good agreement with the experiments. This approach provides a complement to the
      "tension field theory" developed for wrinkles with unconstrained amplitude.

PMID- 23006177
TI  - Creation of prompt and thin-sheet splashing by varying surface roughness or
      increasing air pressure.
AB  - A liquid drop impacting a solid surface may splash either by emitting a thin
      liquid sheet that subsequently breaks apart or by promptly ejecting droplets from
      the advancing liquid-solid contact line. Using high-speed imaging, we show that
      surface roughness and air pressure influence both mechanisms. Roughness inhibits
      thin-sheet formation even though it also increases prompt splashing at the
      advancing contact line. If the air pressure is lowered, droplet ejection is
      suppressed not only during thin-sheet formation but also for prompt splashing.

PMID- 23006178
TI  - Mach-number-invariant mean-velocity profile of compressible turbulent boundary
      layers.
AB  - A series of Mach-number- (M) invariant scalings is derived for compressible
      turbulent boundary layers (CTBLs), leading to a viscosity weighted transformation
      for the mean-velocity profile that is superior to van Driest transformation. The
      theory is validated by direct numerical simulation of spatially developing CTBLs
      with M up to 6. A boundary layer edge is introduced to compare different M flows
      and is shown to better present the M-invariant multilayer structure of CTBLs. The
      new scalings derived from the kinetic energy balance substantiate Morkovin's
      hypothesis and promise accurate prediction of the mean profiles of CTBLs.

PMID- 23006179
TI  - Maxwell's demon in the Ranque-Hilsch vortex tube.
AB  - A theory was developed that explains energy separation in a vortex tube, known as
      one of the Maxwellian demons. It appears that there is a unique relation between
      the pressures in the exits of the vortex tube and its temperatures. Experimental
      results show that the computed and measured temperatures are in very good
      agreement.

PMID- 23006180
TI  - Thermodynamics of angular propulsion in fluids.
AB  - The presented study examines the energetics of confined fluid flow in a rotating
      reference frame. Parallels are drawn to the corresponding scenario of rectilinear
      motion, where ejection of fluid results in linear propulsion of the frame.
      Absorption of flow energy into the frame motion leads to cooling of the ejected
      fluid. Relevance of the observed energetics to the temperature separation
      phenomenon in Ranque-Hilsch vortex tubes is discussed.

PMID- 23006181
TI  - Lower hybrid drift waves: space observations.
AB  - Lower hybrid drift waves (LHDWs) are commonly observed at plasma boundaries in
      space and laboratory, often having the strongest measured electric fields within
      these regions. We use data from two of the Cluster satellites (C3 and C4) located
      in Earth's magnetotail and separated by a distance of the order of the electron
      gyroscale. These conditions allow us, for the first time, to make cross
      spacecraft correlations of the LHDWs and to determine the phase velocity and
      wavelength of the LHDWs. Our results are in good agreement with the theoretical
      prediction. We show that the electrostatic potential of LHDWs is linearly related
      to fluctuations in the magnetic field magnitude, which allows us to determine the
      velocity vector through the relation ?deltaEdt.v = phi(deltaB)(?). The
      electrostatic potential fluctuations correspond to ~10% of the electron
      temperature, which suggests that the waves can strongly affect the electron
      dynamics.

PMID- 23006182
TI  - Viscosity of a strongly coupled dust component in a weakly ionized plasma.
AB  - An experimental study of the kinematic viscosity has been carried out for dust
      particles of size 0.95 and 3.92 MUm, in weakly ionized plasma over a wide range
      of dust coupling parameters. Measurements of viscosity for weakly correlated
      dusty-plasma systems are presented for the first time. An approximation for the
      estimation of viscosity constants is proposed. The measured viscosity constants
      are compared with theoretical estimates and numerical data.

PMID- 23006183
TI  - Quasiparticle dynamics in a bose insulator probed by interband bragg
      spectroscopy.
AB  - We investigate experimentally and theoretically the dynamical properties of a
      Mott insulator in decoupled one-dimensional chains. Using a theoretical analysis
      of the Bragg excitation scheme, we show that the spectrum of interband
      transitions holds information on the single-particle Green's function of the
      insulator. In particular, the existence of particle-hole coherence due to quantum
      fluctuations in the Mott state is clearly seen in the Bragg spectra and
      quantified. Finally, we propose a scheme to directly measure the full, momentum
      resolved spectral function as obtained in the angle-resolved photoemission
      spectroscopy of solids.

PMID- 23006184
TI  - Microscopic model for feshbach interacting fermions in an optical lattice with
      arbitrary scattering length and resonance width.
AB  - We numerically study the problem of two fermions in a three-dimensional optical
      lattice interacting via a zero-range Feshbach resonance and display the
      dispersions of the bound states as a two-particle band structure with unique
      features compared to typical single-particle band structures. We show that the
      exact two-particle solutions of a projected Hamiltonian may be used to define an
      effective two-channel, few-band model for the low-energy, low-density physics of
      many fermions at arbitrary s-wave scattering length. Our method applies to
      resonances of any width and can be adapted to multichannel situations or higher-l
      pairing. In strong contrast to usual Hubbard physics, we find that pair hopping
      is significantly altered by strong interactions and the presence of the lattice,
      and the lattice induces multiple molecular bound states.

PMID- 23006185
TI  - Quantum electronic stress: density-functional-theory formulation and physical
      manifestation.
AB  - The concept of quantum electronic stress (QES) is introduced and formulated
      within density functional theory to elucidate extrinsic electronic effects on the
      stress state of solids and thin films in the absence of lattice strain. A formal
      expression of QES (sigma(QE)) is derived in relation to deformation potential of
      electronic states (Xi) and variation of electron density (Deltan), sigma(QE) =
      XiDeltan as a quantum analog of classical Hooke's law. Two distinct QES
      manifestations are demonstrated quantitatively by density functional theory
      calculations: (1) in the form of bulk stress induced by charge carriers and (2)
      in the form of surface stress induced by quantum confinement. Implications of QES
      in some physical phenomena are discussed to underlie its importance.

PMID- 23006186
TI  - Valley-polarized metals and quantum anomalous Hall effect in silicene.
AB  - Silicene is a monolayer of silicon atoms forming a two-dimensional honeycomb
      lattice, which shares almost every remarkable property with graphene. The low
      energy structure of silicene is described by Dirac electrons with relatively
      large spin-orbit interactions due to its buckled structure. The key observation
      is that the band structure is controllable by applying electric field to
      silicene. We explore the phase diagram of silicene together with exchange field M
      and by applying electric field E(z). A quantum anomalous Hall (QAH) insulator,
      valley polarized metal (VPM), marginal valley polarized metal (M-VPM), quantum
      spin Hall insulator, and band insulator appear. They are characterized by the
      Chern numbers and/or by the edge modes of a nanoribbon. It is intriguing that
      electrons have been moved from a conduction band at the K point to a valence band
      at the K' point for E(z) > 0 in the VPM. We find in the QAH phase that almost
      flat gapless edge modes emerge and that spins form a momentum-space Skyrmion to
      yield the Chern number. It is remarkable that a topological quantum phase
      transition can be induced simply by changing electric field in a single silicene
      sheet.

PMID- 23006187
TI  - Reduced glass transition temperatures in thin polymer films: surface effect or
      artifact?
AB  - We have examined the direct effect of manipulating the number of free surfaces on
      the measured glass transition temperature T(g) of thin polystyrene films. Thin
      films in the range 35 nm < h < 114 nm with molecular weights of 592 kg/mol and
      1144 kg/mol were studied. Ellipsometry was used to determine the temperature
      dependence of the thickness and refractive index of freestanding films. By noting
      the change in slope in each of these quantities, a T(g) value can be assigned in
      quantitative agreement with previously reported results. For thin freestanding
      films this value is reduced from that of the bulk. The exact same films are then
      transferred to a Si substrate and the T(g) of the resulting supported film was
      determined. The T(g) values of the now supported films are the same as the bulk
      value and the same as previous reports of similar supported films. These
      experiments unambiguously show that free interfaces are the dominant cause of the
      T(g) reductions for the film thicknesses studied.

PMID- 23006188
TI  - Entanglement-controlled subdiffusion of nanoparticles within concentrated polymer
      solutions.
AB  - We describe x-ray photon correlation spectroscopy (XPCS) experiments tracking the
      motion of gold nanoparticles within solutions of high-molecular-weight
      polystyrene. Over displacements from nanometers to tens of nanometers, the
      particles undergo subdiffusive motion that is dictated by the temporal evolution
      of the entangled polymer mesh in the immediate vicinity of the particles. The
      results thus provide a novel microscopic dynamical characterization of this key
      structural property of polymers and more broadly demonstrate the capability of
      XPCS-based microrheology to interrogate heterogeneous mechanical environments in
      nanostructured soft materials.

PMID- 23006189
TI  - Nonlinear wavelength selection in surface faceting under electromigration.
AB  - We report on the control of the faceting of crystal surfaces by means of surface
      electromigration. When electromigration reinforces the faceting instability, we
      find perpetual coarsening with a wavelength increasing as t(1/2). For strongly
      stabilizing electromigration, the surface is stable. For weakly stabilizing
      electromigration, a cellular pattern is obtained, with a nonlinearly selected
      wavelength. The selection mechanism is not caused by an instability of steady
      states, as suggested by previous works in the literature. Instead, the dynamics
      is found to exhibit coarsening before reaching a continuous family of stable
      nonequilibrium steady states.

PMID- 23006190
TI  - Self-energy on the low- to high-energy electronic structure of correlated metal
      SrVO3.
AB  - The correlated electronic structure of SrVO(3) has been investigated by angle
      resolved photoemission spectroscopy using in situ prepared thin films. Pronounced
      features of band renormalization have been observed: a sharp kink ~60 meV below
      the Fermi level (E(F)) and a broad so-called "high-energy kink" ~0.3 eV below
      E(F) as in the high-T(c) cuprates, although SrVO(3) does not show magnetic
      fluctuations. We have deduced the self-energy in a wide energy range by applying
      the Kramers-Kronig relation to the observed spectra. The obtained self-energy
      clearly shows a large energy scale of ~0.7 eV, which is attributed to electron
      electron interaction and gives rise to the ~0.3 eV kink in the band dispersion as
      well as the incoherent peak ~1.5 eV below E(F). The present analysis enables us
      to obtain a consistent picture for both the incoherent spectra and the band
      renormalization.

PMID- 23006191
TI  - One-dimensional continuum electronic structure with the density-matrix
      renormalization group and its implications for density-functional theory.
AB  - We extend the density matrix renormalization group to compute exact ground states
      of continuum many-electron systems in one dimension with long-range interactions.
      We find the exact ground state of a chain of 100 strongly correlated artificial
      hydrogen atoms. The method can be used to simulate 1D cold atom systems and to
      study density-functional theory in an exact setting. To illustrate, we find an
      interacting, extended system which is an insulator but whose Kohn-Sham system is
      metallic.

PMID- 23006192
TI  - Two-dimensional charge transport in disordered organic semiconductors.
AB  - We analyze the effect of carrier confinement on the charge-transport properties
      of organic field-effect transistors. Confinement is achieved experimentally by
      the use of semiconductors of which the active layer is only one molecule thick.
      The two-dimensional confinement of charge carriers provides access to a
      previously unexplored charge-transport regime and is reflected by a reduced
      temperature dependence of the transfer curves of organic monolayer transistors.

PMID- 23006193
TI  - Transconductance fluctuations as a probe for interaction-induced quantum Hall
      states in graphene.
AB  - Transport measurements normally provide a macroscopic, averaged view of the
      sample so that disorder prevents the observation of fragile interaction-induced
      states. Here, we demonstrate that transconductance fluctuations in a graphene
      field effect transistor reflect charge localization phenomena on the nanometer
      scale due to the formation of a dot network which forms near incompressible
      quantum states. These fluctuations give access to fragile broken symmetry and
      fractional quantum Hall states even though these states remain hidden in
      conventional magnetotransport quantities.

PMID- 23006194
TI  - Experimental evidence for quantum interference and vibrationally induced
      decoherence in single-molecule junctions.
AB  - We analyze quantum interference and decoherence effects in single-molecule
      junctions both experimentally and theoretically by means of the mechanically
      controlled break junction technique and density-functional theory. We consider
      the case where interference is provided by overlapping quasidegenerate states.
      Decoherence mechanisms arising from electronic-vibrational coupling strongly
      affect the electrical current flowing through a single-molecule contact and can
      be controlled by temperature variation. Our findings underline the universal
      relevance of vibrations for understanding charge transport through molecular
      junctions.

PMID- 23006195
TI  - Semiconductor quantized voltage source.
AB  - We realize and investigate an all-semiconductor quantized voltage source which
      generates quantized output voltages V(out) = f(h/e) linked only to two
      fundamental constants, the electron's charge e and Planck's constant h, and to an
      applied excitation frequency f. The device is based on an integrated quantized
      circuit of a single-electron pump operated at pumping frequency f and a quantum
      Hall device monolithically integrated in series. Robust output voltages up to
      several MUV are generated, which are expected to be scalable by orders of
      magnitude using present technology. The device might open a new route towards the
      closure of the quantum metrology triangle.

PMID- 23006196
TI  - Unconventional Josephson effect in hybrid superconductor-topological insulator
      devices.
AB  - We report on transport properties of Josephson junctions in hybrid
      superconducting-topological insulator devices, which show two striking departures
      from the common Josephson junction behavior: a characteristic energy that scales
      inversely with the width of the junction, and a low characteristic magnetic field
      for suppressing supercurrent. To explain these effects, we propose a
      phenomenological model which expands on the existing theory for topological
      insulator Josephson junctions.

PMID- 23006197
TI  - Evidence for Dirac fermions in a honeycomb lattice based on silicon.
AB  - Silicene, a sheet of silicon atoms in a honeycomb lattice, was proposed to be a
      new Dirac-type electron system similar to graphene. We performed scanning
      tunneling microscopy and spectroscopy studies on the atomic and electronic
      properties of silicene on Ag(111). An unexpected ?3 * ?3 reconstruction was
      found, which is explained by an extra-buckling model. Pronounced quasiparticle
      interferences (QPI) patterns, originating from both the intervalley and
      intravalley scatter, were observed. From the QPI patterns we derived a linear
      energy-momentum dispersion and a large Fermi velocity, which prove the existence
      of Dirac fermions in silicene.

PMID- 23006198
TI  - Hot electron cooling by acoustic phonons in graphene.
AB  - We have investigated the energy loss of hot electrons in metallic graphene by
      means of GHz noise thermometry at liquid helium temperature. We observe the
      electronic temperature T ? V at low bias in agreement with the heat diffusion to
      the leads described by the Wiedemann-Franz law. We report on T ? ?V behavior at
      high bias, which corresponds to a T(4) dependence of the cooling power. This is
      the signature of a 2D acoustic phonon cooling mechanism. From a heat equation
      analysis of the two regimes we extract accurate values of the electron-acoustic
      phonon coupling constant Sigma in monolayer graphene. Our measurements point to
      an important effect of lattice disorder in the reduction of Sigma, not yet
      considered by theory. Moreover, our study provides a strong and firm support to
      the rising field of graphene bolometric detectors.

PMID- 23006199
TI  - Electron-phonon coupling in the conventional superconductor YNi2B2C at high
      phonon energies studied by time-of-flight neutron spectroscopy.
AB  - We report an inelastic neutron scattering investigation of phonons with energies
      up to 159 meV in the conventional superconductor YNi(2)B(2)C. Using the sweep
      mode, a newly developed time-of-flight technique involving the continuous
      rotation of a single crystal specimen, allowed us to measure a four-dimensional
      volume in (Q, E) space and, thus, determine the dispersion surface and linewidths
      of the A(1g) (~102 meV) and A(u) (~159 meV) type phonon modes over the whole
      Brillouin zone. Despite of having linewidths of Gamma=10 meV, A(1g) modes do not
      strongly contribute to the total electron-phonon coupling constant lambda.
      However, experimental linewidths show a remarkable agreement with ab initio
      calculations over the complete phonon energy range, demonstrating the accuracy of
      such calculations in a rare comparison to a comprehensive experimental data set.

PMID- 23006200
TI  - Andreev current induced by ferromagnetic resonance.
AB  - We study charge transport through a metallic dot coupled to a superconducting and
      a ferromagnetic lead with a precessing magnetization due to ferromagnetic
      resonance. Using the quasiclassical theory, we find that the magnetization
      precession induces a dc current in the subgap regime even in the absence of a
      bias voltage. This effect is due to the rectification of the ac spin currents at
      the interface with the ferromagnet; it exists in the absence of spin current in
      the superconductor. When the dot is strongly coupled to the superconductor, we
      find a strong enhancement in a wide range of parameters as compared to the
      induced current in the normal state.

PMID- 23006201
TI  - KFe2Se2 is the parent compound of K-doped iron selenide superconductors.
AB  - We elucidate the existing controversies in the newly discovered K-doped iron
      selenide (K(x)Fe(2-y)Se(2-z)) superconductors. The stoichiometric KFe(2)Se(2)
      with ?2 * ?2 charge ordering was identified as the parent compound of K(x)Fe(2
      y)Se(2-z) superconductor using scanning tunneling microscopy and spectroscopy.
      The superconductivity is induced in KFe(2)Se(2) by either Se vacancies or
      interacting with the antiferromagnetic K(2)Fe(4)Se(5) compound. In total, four
      phases were found to exist in K(x)Fe(2-y)Se(2-z): parent compound KFe(2)Se(2),
      superconducting KFe(2)Se(2) with ?2 * ?5 charge ordering, superconducting
      KFe(2)Se(2-z) with Se vacancies, and insulating K(2)Fe(4)Se(5) with ?5 * ?5 Fe
      vacancy order. The phase separation takes place at the mesoscopic scale under
      standard molecular beam epitaxy conditions.

PMID- 23006202
TI  - Large magnetoresistance oscillations in mesoscopic superconductors due to current
      excited moving vortices.
AB  - We show in the case of a superconducting Nb ladder that a mesoscopic
      superconductor typically exhibits magnetoresistance oscillations whose amplitude
      and temperature dependence are different from those stemming from the Little
      Parks effect. We demonstrate that these large resistance oscillations (as well as
      the monotonic background on which they are superimposed) are due to current
      excited moving vortices, where the applied current in competition with the
      oscillating Meissner currents imposes or removes the barriers for vortex motion
      in an increasing magnetic field. Because of the ever present current in transport
      measurements, this effect should be considered in parallel with the Little-Parks
      effect in low-critical temperature (T(c)) samples, as well as with recently
      proposed thermal activation of dissipative vortex-antivortex pairs in high-T(c)
      samples.

PMID- 23006203
TI  - Evidence for triplet superconductivity in a superconductor-ferromagnet spin
      valve.
AB  - We have studied the dependence of the superconducting (SC) transition temperature
      on the mutual orientation of magnetizations of Fe1 and Fe2 layers in the spin
      valve system CoO(x)/Fe1/Cu/Fe2/Pb. We find that this dependence is nonmonotonic
      when passing from the parallel to the antiparallel case and reveals a distinct
      minimum near the orthogonal configuration. The analysis of the data in the
      framework of the SC triplet spin valve theory gives direct evidence for the long
      range triplet superconductivity arising due to noncollinearity of the two
      magnetizations.

PMID- 23006204
TI  - Finite-temperature transition of the antiferromagnetic Heisenberg model on a
      distorted kagome lattice.
AB  - Motivated by the recent experiment on kagome-lattice antiferromagnets, we study
      the zero-field ordering behavior of the antiferromagnetic classical Heisenberg
      model on a uniaxially distorted kagome lattice by Monte Carlo simulations. A
      first-order transition, which has no counterpart in the corresponding undistorted
      model, takes place at a very low temperature. The origin of the transition is
      ascribed to a cooperative proliferation of topological excitations inherent to
      the model.

PMID- 23006205
TI  - Femtosecond laser excitation drives ferromagnetic gadolinium out of magnetic
      equilibrium.
AB  - The temporal evolution of the exchange-split Delta(2)-like Sigma valence bands of
      the 4f-ferromagnet gadolinium after femtosecond laser excitation has been studied
      using angle-resolved photoelectron spectroscopy based on high-order harmonic
      generation. The ultrafast drop of the exchange splitting reflects the magnetic
      response seen in femtosecond magnetic dichroism experiments. However, while the
      minority valence band reacts immediately, the response of the majority
      counterpart is delayed by 1 picosecond and is only half as fast. These findings
      demonstrate that laser excitation drives the valence band structure out of
      magnetic equilibrium.

PMID- 23006206
TI  - Direct-gap gain and optical absorption in germanium correlated to the density of
      photoexcited carriers, doping, and strain.
AB  - Direct-gap gain up to 850 cm(-1) at 0.74 eV is measured and modeled in optically
      pumped Ge-on-Si layers for photoexcited carrier densities of 2.0 * 10(20) cm(-3).
      The gain spectra are correlated to carrier density via plasma-frequency
      determinations from reflection spectra. Despite significant gain, optical
      amplification cannot take place, because the carriers also generate pump-induced
      absorption of ~7000 cm(-1). Parallel studies of III-V direct-gap InGaAs layers
      validate our spectroscopy and modeling. Our self-consistent results contradict
      current explanations of lasing in Ge-on-Si cavities.

PMID- 23006207
TI  - Experimental and theoretical evidence of a highly ordered two-dimensional Sn/Ag
      alloy on Si111.
AB  - The existence of a highly ordered, two-dimensional, Sn/Ag alloy on Si(111) is
      reported in this study. We present detailed atomic and electronic structures of
      the one atomic layer thick alloy, exhibiting a 2 * 2 periodicity. The electronic
      structure is metallic due to a free-electron-like surface band dispersing across
      the Fermi level. By electron doping, the electronic structure can be converted
      into a semiconducting state. A rotated Sn trimer constitutes the key structural
      element that could be identified by a detailed analysis of constant energy
      contours derived from the free-electron-like band.

PMID- 23006208
TI  - Revisiting properties of ferroelectric and multiferroic thin films under tensile
      strain from first principles.
AB  - First-principles calculations are performed to revisit properties of (001)
      epitaxial BiFeO(3) (BFO) and PbTiO(3) thin films under tensile strain. While
      these two films possess different ground states when experiencing no misfit
      strain, they both exhibit the same, previously unknown phase for tensile strains
      above ?5% at T = 0 K. This novel state is of orthorhombic Pmc2(1) symmetry and is
      macroscopically characterized by a large in-plane polarization coexisting with
      oxygen octahedra tilting in-phase about the out-of-plane direction. On a
      microscopic point of view, this Pmc2(1) state exhibits short atomic bonds and
      zigzag cation displacement patterns, unlike conventional ferroelectric phases and
      typical domains. Such unusual inhomogeneous patterns originate from the
      coexistence of polar and antiferroelectric distortions having the same magnitude
      and lead BFO films to be the first known material for which orbital ordering
      coexists with a large polarization. Furthermore, this Pmc2(1) state is also found
      in other perovskite films under tensile strain, which emphasizes its generality.

PMID- 23006209
TI  - Single-molecule study of G-quadruplex disruption using dynamic force
      spectroscopy.
AB  - Guanine-rich sequences in nucleic acids can fold into G quadruplexes, in which
      four guanines on a single strand combine to form G-tetrad planes stabilized by
      metallic ions. Sequence motifs which are predicted to form a G quadruplex are
      found throughout the genome and are believed to regulate a variety of biological
      processes. Detailed knowledge of the kinetics of G-quadruplex folding and
      unfolding would provide critical insight into these processes. To probe its
      structural stability, we used optical tweezers to disrupt single molecules of a
      single-stranded DNA G4 quadruplex. Dynamic force spectroscopy was employed, in
      which the distribution of rupture forces was measured for different loading rates
      and used to infer the nature of the transition state barrier for unfolding of the
      structure. The distance and height of the energy barriers were extracted for two
      observed conformations. The energy barrier was found to be close to the folded
      conformation, resulting in a high disruption force despite the relatively low
      energy barrier height.

PMID- 23006210
TI  - Lipid bilayers and membrane dynamics: insight into thickness fluctuations.
AB  - Thickness fluctuations have long been predicted in biological membranes but never
      directly observed experimentally. Here, we utilize neutron spin echo spectroscopy
      to experimentally reveal such fluctuations in a pure, fully saturated,
      phosphocholine lipid bilayer system. These fluctuations appear as an excess in
      the dynamics of undulation fluctuations. Like the bending rigidity, the thickness
      fluctuations change dramatically as the lipid transition temperature is crossed,
      appearing to be completely suppressed below the transition. Above the transition,
      the relaxation rate is on the order of 100 ns and is independent of temperature.
      The amplitude of the thickness fluctuations is 3.7 A +/- 0.7 A, which agrees well
      with theoretical calculations and molecular dynamics simulations. The dependence
      of the fluctuations on lipid tail lengths is also investigated and determined to
      be minimal in the range of 14 to 18 carbon tails.

PMID- 23006211
TI  - Experimental observation of directional locking and dynamical ordering of
      colloidal monolayers driven across quasiperiodic substrates.
AB  - We experimentally investigate the structural behavior of an interacting colloidal
      monolayer being driven across a decagonal quasiperiodic potential landscape
      created by an optical interference pattern. When the direction of the driving
      force is varied, we observe the monolayer to be directionally locked on angles
      corresponding to the symmetry axes of the underlying potential. At such locking
      steps, we observe a dynamically ordered smectic phase in agreement with recent
      simulations. We demonstrate that such dynamical ordering is due to the
      interaction of particle lanes formed by interstitial and noninterstitial
      particles.

PMID- 23006212
TI  - Comment on "Fast and accurate modeling of molecular atomization energies with
      machine learning".

PMID- 23006215
TI  - Air pollution, vascular disease and thrombosis: linking clinical data and
      pathogenic mechanisms.
AB  - The public health burden of air pollution has been increasingly recognized over
      the last decades. Following the first assessed adverse effects on respiratory
      diseases and lung cancer, a large body of epidemiologic and clinical studies
      definitely documented an even stronger association of air pollution exposure with
      cardiovascular mortality and morbidity, particularly related to atherothrombotic
      (coronary and cerebrovascular) disease. Particulate matter (PM), mainly that with
      lower aerodynamic diameter (fine and ultrafine PM), is responsible for the most
      severe effects, due to its capacity to transport toxic substances deep into the
      lower airways. These effects have been shown to occur not only after short-term
      exposure to elevated concentrations of pollutants, but even after long-term
      relatively low levels of exposure. Vulnerable subjects (elderly persons and those
      with preexisting cardiopulmonary diseases) show the highest impact. Fewer and
      conflicting data also suggest an association with venous thromboembolism.
      Although not completely elucidated, a series of mechanisms have been hypothesized
      and tested in experimental settings. These phenomena, including vasomotor and
      cardiac autonomic dysfunction, hemostatic unbalance, oxidative stress and
      inflammatory response, have been shown to change over time and differently
      contribute to the short-term and long-term adverse effects of pollution exposure.
      Beyond environmental health policies, crucial for improving air quality and
      reducing the impact of such an elusive threat to public health, the recognition
      and assessment of the individual risk, together with specific advice, should be
      routinely implemented in the strategies of primary and secondary cardiovascular
      prevention.

PMID- 23006214
TI  - Serum-free medium and mesenchymal stromal cells enhance functionality and
      stabilize integrity of rat hepatocyte spheroids.
AB  - Long-term culture of hepatocyte spheroids with high ammonia clearance is valuable
      for therapeutic applications, especially the bioartificial liver. However, the
      optimal conditions are not well studied. We hypothesized that liver urea cycle
      enzymes can be induced by high protein diet  and maintain on a higher expression
      level in rat hepatocyte spheroids by serum-free medium (SFM) culture and
      coculture with mesenchymal stromal cells (MSCs). Rats were feed normal protein
      diet (NPD) or high protein diet (HPD) for 7 days before liver digestion and
      isolation of hepatocytes.  Hepatocyte spheroids were formed and maintained in a
      rocked suspension culture with or without MSCs in SFM or 10% serum-containing
      medium (SCM). Spheroid viability, kinetics of spheroid formation, hepatic
      functions, gene expression, and biochemical activities of rat hepatocyte
      spheroids were  tested over 14 days of culture. We observed that urea cycle
      enzymes of hepatocyte spheroids can be induced by high protein diet. SFM and MSCs
      enhanced ammonia clearance and ureagenesis and stabilized integrity of hepatocyte
      spheroids compared to control conditions over 14 days. Hepatocytes  from high
      protein diet-fed rats formed spheroids and maintained a high level of ammonia
      detoxification for over 14 days in a novel SFM. Hepatic functionality and
      spheroid integrity were further stabilized by coculture of hepatocytes with MSCs
      in the spheroid microenvironment. These findings  have direct application to
      development of the spheroid reservoir bioartificial liver.

PMID- 23006217
TI  - Chronic electrical stimulation of transected peripheral nerves preserves anatomy
      and function in the primary somatosensory cortex.
AB  - The structure and function of the central nervous system strongly depend on the
      organization and efficacy of the incoming sensory input. A disruption of
      somesthetic input severely alters the metabolic activity, electrophysiological
      properties and even gross anatomical features of the primary somatosensory
      cortex. Here we examined, in the rat somatosensory cortex, the neuroprotective
      and therapeutic effects of artificial sensory stimulation after irreversible
      unilateral transection of a peripheral sensory nerve (the infraorbital branch of
      the trigeminal nerve). The proximal stump of the nerve was inserted into a
      silicon tube with stimulating electrodes, through which continuous electrical
      stimulation was applied for 12 h/day (square pulses of 100 MUs, 3.0 V, at 20 Hz)
      for 4 weeks. Deafferented animals showed significant decreases in cortical evoked
      potentials, cytochrome oxidase staining intensity (layers II-IV), cortical volume
      (layer IV) and number of parvalbumin-expressing (layers II-IV) and calbindin-D28k
      expressing (layers II/III) interneurons. These deafferentation-dependent effects
      were largely absent in the nerve-stimulated animals. Together, these results
      provide evidence that chronic electrical stimulation has a neuroprotective and
      preservative effect on the sensory cortex, and raise the possibility that, by
      controlling the physical parameters of an artificial sensory input to a sectioned
      peripheral nerve, chronically deafferented brain regions could be maintained at
      near-'normal' conditions. Our findings could be important for the design of
      sensory neuroprostheses and for therapeutic purposes in brain lesions or neural
      degenerative processes.

PMID- 23006216
TI  - Effect of low dose mineralocorticoid receptor antagonist eplerenone on glucose
      and lipid metabolism in healthy adult males.
AB  - Mineralocorticoid Receptor (MR) activation is involved in blood pressure
      regulation and the pathogenesis of cardiovascular diseases, such as cardiac
      fibrosis, vascular inflammation and arterial aging. Recent investigations suggest
      a role for MR activation in metabolic dysregulation. OBJECTIVE: To test the
      effect of MR blockade on basal and postprandial glucose and lipid levels after a
      meal high in fat and glucose in healthy males. SUBJECTS AND METHODS: A
      prospective, self-controlled study was performed in 13 healthy adult males aged
      18-45years. Blood was drawn before, 2h, and 4h after a high fat/high glucose meal
      (50g fat, 75g glucose), followed by low-dose eplerenone treatment (50mg daily)
      for 14days. Subjects returned for a second high fat/high glucose meal after the
      medication period. Basal and postprandial blood glucose and lipid levels were
      compared before and after eplerenone treatment. RESULTS: Eplerenone treatment
      affected neither basal nor postprandial glucose and lipid levels in our study
      population. CONCLUSION: Our results suggest that low-dose, non-blood pressure
      affecting, MR blockade does not alter postprandial lipid and glucose homeostasis
      in healthy adult subjects.

PMID- 23006218
TI  - Long-term clinical outcomes and survivorship after total knee arthroplasty using
      a rotating platform knee prosthesis: a meta-analysis.
AB  - A systematic search identified 29 papers reporting survivorship and clinical and
      function Knee Society Scores (KSS) of 6437 total knee replacements using the Low
      Contact Stress (LCS) Rotating Platform (RP) mobile bearing knee. Low Contact
      Stress RP survivorship and KSS outcomes were compared with non-LCS knees in the
      Swedish knee registry at comparable time periods and in 2 independent systematic
      reviews of knee arthroplasty outcomes. There is a substantial body of mainly
      observational evidence supporting the LCS RP knee. Knee Society Score outcomes
      were comparable for LCS RP and non-LCS RP knees at up to 15 years of follow-up,
      with mean clinical and function scores ranging from 72 to 96 and 58 to 90,
      respectively. Survivorship of LCS RP knees up to 14 years was higher than that
      for all knees in the Swedish Knee Registry.

PMID- 23006219
TI  - [Insulin pump treatment is a growing form of therapy].

PMID- 23006220
TI  - [Supervised injecting facilities, voluntary action and civil disobedience].

PMID- 23006221
TI  - [The initial experience in supervised injecting facilities in Denmark].
AB  - Intravenous drug abuse is a major health concern. The National Board of Health
      estimates the number of injecting drug users (IDUs) in Denmark to be 13,000.
      Supervised injecting facilities (SIF) reduce the risk behaviour and bacterial
      infections and also increase the rate of detoxification and access to health
      care. The first SIF in Denmark is driven by volunteers and it opened in September
      2011. In the first six months there were 1,139 visits. As in earlier studies the
      IDUs were mainly males with a long history of drug use. Unlike in previously
      published studies cocaine was the most commonly injected drug.

PMID- 23006222
TI  - [Adverse events associated with long-term use of proton pump inhibitors].
AB  - Proton pump inhibitors (PPI) remain the leading therapy for acid-related
      disorders. Long-term PPI use increases the risk of pneumonia and enteric
      bacterial infections and of nosocomial Clostridium difficile-associated
      diarrhoea. PPIs do not lead to vitamin B12 or iron deficiencies and do not induce
      malignancies or increase the risk of major birth defects. Prolonged PPI use may
      be a weak risk factor for certain fractures and results in hypergastrinaemia and
      parietal cell hyperplasia leading to rebound acid hypersecretion, which may
      induce symptoms on withdrawal of therapy.

PMID- 23006223
TI  - [Coffee can protect against disease].
AB  - A moderate daily intake of 3-4 cups of coffee has convincing protective effects
      against development of type 2 diabetes and Parkinson's disease. The literature
      also indicates that moderate coffee intake reduces the risk of stroke, the
      overall risk of cancer, Alzheimer's disease, suicide and depression. However,
      pregnant women, people suffering from anxiety disorder and persons with a low
      calcium intake should restrain from moderate or high intake of coffee due to
      uncertainty regarding potential negative effects on pregnancy, anxiety and risk
      of osteoporosis, respectively.

PMID- 23006224
TI  - [Prehospital treatment of intoxications with euphorizing drugs].
AB  - Acute intoxications are frequently seen in the prehospital setting and are often
      either a mixture of multiple drugs or supplemented with other drugs such as
      alcohol or marihuana. In contrast to the in-hospital setting, where intoxications
      can be detected with blood, sweat or urine tests, the prehospital physician may
      need to act on the symptomatology rather than the aetiology. Symptoms can be
      divided into two main groups depending on whether they are promoting or
      inhibiting vital functions. This article gives an update on management of
      intoxications with central stimulants in the prehospital setting.

PMID- 23006225
TI  - [Narcolepsy in a seven-year-old girl].
AB  - Narcolepsy is a life-long disease commonly diagnosed in adults. Although the
      first symptoms often appear during childhood, paediatric narcolepsy is often
      underrecognised and underdiagnosed. The presentation can be very variable, this
      making diagnosis difficult. We describe a paediatric case with narcolepsy. The
      patient had the typical symptoms with excessive daytime sleepiness, sleep attacks
      and cataplexy. The aim of this case report is to draw paediatricians' attention
      to childhood narcolepsy. An early and sufficient treatment is necessary to avoid
      socio-emotional disorders and poor school performance in these patients.

PMID- 23006226
TI  - [A solitary ganglioneuroma occurring in the sigmoid colon].
AB  - We report a case of a rare solitary ganglioneuroma occurring in the sigmoid colon
      of a 70-year-old woman. She experienced sudden onset of abdominal pain and loss
      of old blood from the gastrointestinal tract. A colonoscopy disclosed a
      pedunculate polyp in the sigmoid colon 20 cm from the anus, and a histopathologic
      examination revealed a polypoid mucosa with abundant ganglionic cells and nerve
      fibres.

PMID- 23006227
TI  - [Primary clear cell adenocarcinoma of the colon].
AB  - Clear cell adenocarcinoma generally develops in the kidney and the female genital
      organs. In 1964 the first case of primary clear cell adenocarcinoma of the colon
      was described. Since then less than 20 cases have been reported in the
      literature. We report a case of a 69-year-old man with a primary clear cell
      adenocarcinoma of the colon sigmoideum associated with adenoma and metastasis to
      two of 12 lymph nodes. Immunhistochemistry supported the diagnosis. The patient
      received adjuvant chemotherapy and 19 months following operation he was alive and
      had no signs of recurrences.

PMID- 23006228
TI  - [Development of a perforated peptic ulcer in a child during high dose
      prednisolone treatment].
AB  - Since perforated peptic ulcer is uncommon in children proton pump inhibitor
      prophylaxis is not routinely recommended when children are treated with high dose
      steroids. We describe a case of perforated ulcer in a six-year-old patient with
      nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not
      suspected due to uncharacteristic symptoms. The child developed peritoneal signs
      and surgery revealed a perforated peptic ulcer in the stomach. We recommend
      treatment with proton pump inhibitors if children, who are treated with high dose
      steroids develop abdominal symptoms, which can be caused by an ulcus.

PMID- 23006229
TI  - [Atypical primary symptom in the form of peripheral embolisation after painless
      myocardial infarction].
AB  - We report a case with peripheral embolisation as the primary symptom of a
      painless myocardial infarction with left ventricular mural thrombosis. The
      patient was suffering from severe pain in his leg due to arterial occlusion.
      Subsequent electrocardiography and echocardiography documented severe damage to
      the left ventricle and a big motile mural thrombosis. A coronary angiography
      showed subtotal occlusion of the left descending artery. Patients presenting with
      peripheral thromboembolic episodes should be examined for cardiac cause even in
      the absence of cardiac symptoms.

PMID- 23006230
TI  - [Pneumothorax caused by penetrating pacemaker].

PMID- 23006231
TI  - Determinants of heart rate recovery in coronary artery disease patients with and
      without type 2 diabetes.
AB  - Cardiovascular autonomic dysfunction, which is a common complication of diabetes,
      is associated with increased mortality in patients with coronary artery disease
      (CAD). However, the reasons of autonomic dysfunction in CAD patients with or
      without diabetes are not well known. We examine the association between heart
      rate recovery (HRR) and other potential factors among CAD patients with and
      without type 2 diabetes (T2D). Correlations between HRR 60s after exercise
      (HRR(60)), characteristics, laboratory and echocardiographic variables, exercise
      capacity and physical activity were assessed in 50 CAD patients with T2D and 55
      patients with CAD alone. HRR(60) had the closest univariate correlation with
      physical activity and exercise capacity in patients with T2D (r=0.38, p=0.006 and
      r=0.37, p=0.008, respectively). Age, exercise capacity and high-density
      lipoprotein cholesterol level explained 30% of the HRR(60) in patients with T2D
      (p=0.001), while the high intensity physical activity was the only predictor of
      HRR(60) in CAD patients (12%, p=0.010). HRR(60) was reduced in patients with T2D
      as compared with those without (34+/-9 vs. 39+/-9bpm, p=0.005), but the
      difference was no longer significant after adjustments for physical activity,
      exercise capacity, body mass index and the use of calcium antagonists and
      nitrates (p=0.273). In conclusion, blunted HRR is more common among CAD patients
      with T2D than in those without, and this is more closely related to physical
      activity and obesity than to the duration of T2D or associated co-morbidities.

PMID- 23006232
TI  - Emergence of multiresistant methicillin-resistant Staphylococcus aureus in two
      patients with atopic dermatitis requiring linezolid treatment.
AB  - We report two patients with atopic dermatitis who developed methicillin-resistant
      Staphylococcus aureus (MRSA) skin infections resistant to clindamycin and
      trimethoprim-sulfamethoxazole requiring repeated linezolid treatment. For one
      patient and family members who received an aggressive regimen of staphylococcal
      decolonization, including intranasal mupirocin, dilute bleach baths, and bleach
      cleansing of household items and surfaces, subsequent culture results
      demonstrated methicillin-susceptible S. aureus colonization and infection. These
      findings underscore the challenges presented by multiresistant MRSA infections in
      children with atopic dermatitis. 

PMID- 23006235
TI  - Advantages and limitations of newer antipsychotics: evidence from large
      comparative trials.

PMID- 23006236
TI  - Optimizing outcome with antipsychotic treatment in first-episode schizophrenia:
      balancing efficacy and side effects.
AB  - The initial tailoring of antipsychotic medication for an individual experiencing
      a first episode of psychosis (FEP) is a critical empirical process with
      potentially far-reaching consequences. This article reviews the results of
      randomized treatment trials of clinically available first-generation
      antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in individuals
      experiencing FEP, addressing these medications' relative therapeutic potentials
      and their proclivities to produce a range of unwanted side effects. The authors
      will argue that the best clinical long-term outcomes will be achieved with: 1) a
      "succeed-first" strategy of identifying those treatment-responsive individuals
      who will have a good response to neuroleptic threshold doses of well-tolerated
      FGAs (thereby avoiding weight gain, insulin resistance, and prolactin-induced
      changes in gender-specific physiology); and, 2) an early trial of clozapine in
      treatment-nonresponsive FEP patients.

PMID- 23006237
TI  - New serotonin/dopamine antagonists for the treatment of schizophrenia: are we
      making real progress?
AB  - The introduction of second-generation antipsychotics (SGAs), heralded by
      clozapine in 1990, represented an important advance in the pharmacologic
      treatment of schizophrenia. However, several recent comparative effectiveness
      trials found that non-clozapine SGAs provided little or no advantage in efficacy
      over first-generation antipsychotics, and all agents had substantial safety and
      tolerability concerns. Clearly, there remains a great unmet need for more
      effective and better-tolerated antipsychotics. Relatively potent antagonism of
      serotonin 5-HT2A receptors coupled with relatively weaker antagonism of dopamine
      D2 receptors is the central pharmacological characteristic shared by most SGAs.
      This profile continues to be a favored model for developing new SGAs, commonly
      defined as serotonin/dopamine antagonists. In the past ten years, aripiprazole,
      paliperidone, asenapine, iloperidone, and lurasidone have been introduced.
      Studies suggest that the newer agents have similar short-term efficacy to earlier
      serotonin/dopamine antagonists, and several demonstrate at least modest
      improvements in safety and tolerability profiles, particularly metabolic
      measures. However, as a group, the newer serotonin/dopamine antagonists are
      pharmacologically heterogeneous, and their side-effect burden can still be
      considerable. Moreover, their putative clinical advantages have not yet been well
      demonstrated via direct comparative studies. The absence of such evidence adds to
      the challenges in defining their place among more established treatment choices,
      or in providing clinicians with clear indications to guide treatment choices for
      individual patients. Long-term, head-to-head comparative studies are required to
      clarify the risk/benefit profiles of the newer antipsychotics and their roles in
      the treatment of schizophrenia.

PMID- 23006238
TI  - Clozapine: balancing safety with superior antipsychotic efficacy.
AB  - Clozapine is often referred to as the gold standard for the treatment of
      schizophrenia and yet has also been described as the most underutilized treatment
      for schizophrenia supported by solid evidence-based medicine. In 2008, it was
      used to treat only 4.4% of patients with schizophrenia in the U.S., which is ~10
      20% of those with approved indications for clozapine for which there is no
      alternative of equal efficacy. Its use is much higher in Scandinavian countries
      and China. The primary indications for clozapine are: 1) treatment-resistant
      schizophrenia or schizoaffective disorder, defined as persistent moderate to
      severe delusions or hallucinations despite two or more clinical trials with other
      antipsychotic drugs; and, 2) patients with schizophrenia or schizoaffective
      disorder who are at high risk for suicide. Concerns over a number of safety
      considerations are responsible for much of the underutilization of clozapine: 1)
      agranulocytosis; 2) metabolic side effects; and, 3) myocarditis. These side
      effects can be detected, prevented, minimized and treated, but there will be a
      very small number of fatalities. Nevertheless, clozapine has been found in two
      large epidemiologic studies to have the lowest mortality of any antipsychotic
      drug, mainly due to its very large effect to reduce the risk for suicide. Other
      reasons for limited use of clozapine include the extra effort entailed in
      monitoring white blood cell counts to detect granulocytopenia or agranulocytosis
      and, possibly, minimal efforts to market it now that it is largely generic.
      Awareness of the benefits and risks of clozapine is essential for increasing the
      use of this lifesaving agent.

PMID- 23006239
TI  - Phenomenology of first-episode psychosis in schizophrenia, bipolar disorder, and
      unipolar depression: a comparative analysis.
AB  - OBJECTIVE: This study sought to identify similarities and differences in symptom
      characteristics at initial presentation of first psychotic episodes in
      schizophrenia, bipolar disorder and unipolar depression. METHODS: The Structured
      Interview for DSM-IV (SCID) and Positive and Negative Syndrome Scale (PANSS) were
      administered to consecutive admission study-eligible patients (n=101) presenting
      for treatment during their first acute phase of psychotic illness. Forty-nine
      percent of patients met diagnostic criteria for schizophrenia, 29% for psychotic
      bipolar disorder and 22% for unipolar depression with psychosis. The PANSS was
      analyzed using five-factor scoring that included Positive, Negative, Cognitive,
      Excitement, and Depression factors, and composite cluster scores that assessed
      Anergia, Thought Disturbance, and Paranoia. RESULTS: Schizophrenia and bipolar
      disorder patients demonstrated significantly more Positive symptoms, Thought
      Disturbance and Paranoia than unipolar depressed patients. Schizophrenia and
      unipolar depressed patients demonstrated significantly more Negative symptoms and
      Anergia than bipolar patients. Patients with schizophrenia reported more severe
      Cognitive Disorganization than patients with either bipolar disorder or uni-polar
      depression (p<.05). CONCLUSIONS: Findings from this study demonstrate an
      informative pattern of similarities and differences in the phenomenology of
      psychotic disorders at first illness presentation. Commonalities in symptom
      profiles reflect considerable symptom overlap among psychotic disorders and,
      thus, the importance of multidimensional differential diagnosis for these
      conditions. The differences across disorders in Positive and Negative symptom
      severity, Thought Disorder, Paranoia, and Anergia, and especially the higher
      level of Cognitive Disorganization seen in schizophrenia patients, point to
      clinically informative differences across these disorders that are relevant to
      clinical diagnostic practice and models of psychopathology.

PMID- 23006240
TI  - Analogies between synthetic and biosynthetic reactions in which [1,2]-alkyl
      shifts are combined with other events: dyotropic, Schmidt, and carbocation
      rearrangements.
AB  - A survey of computational studies on the mechanisms of dyotropic, Schmidt, and
      related reactions is presented. Connections between synthetically applied
      versions of these processes and those predicted to occur during biosynthetic
      terpene-forming carbocation cascades are highlighted.

PMID- 23006241
TI  - Towards increased data transmission rate for a three-class metabolic brain
      computer interface based on transcranial Doppler ultrasound.
AB  - In this study, we conducted an offline analysis of transcranial Doppler (TCD)
      ultrasound recordings to investigate potential methods for increasing data
      transmission rate in a TCD-based brain-computer interface. Cerebral blood flow
      velocity was recorded within the left and right middle cerebral arteries while
      nine able-bodied participants alternated between rest and two different mental
      activities (word generation and mental rotation). We differentiated these three
      states using a three-class linear discriminant analysis classifier while the
      duration of each state was varied between 5 and 30s. Maximum classification
      accuracies exceeded 70%, and data transmission rate was maximized at 1.2 bits per
      minute, representing a four-fold increase in data transmission rate over previous
      two-class analysis of TCD recordings.

PMID- 23006242
TI  - Family and social aspects associated with depression among older persons in a
      Chinese context.
AB  - AIM: This study aims to explore the factors associated with depression among
      older persons in Macau, in relation to family and social aspects. BACKGROUND:
      Depression among community-dwelling older persons in Macau has been shown to be
      present at high rates. In Chinese culture, depression leads to social
      stigmatisation, suggesting a need to better understand depression as a
      sociocultural phenomenon. METHODS: A mixed methods study was undertaken to
      identify the key influences on depression among Chinese older persons in Macau.
      Quantitative (standardised tests) and qualitative (collection of narratives) data
      were collected from 31 purposively selected participants, all community-dwelling
      older persons with depression. RESULTS: Depression was common among the
      participants. The paper reports on the family and social aspects, one of the
      findings of the study. Informants readily described their thoughts and judgements
      of themselves in graphic language. As they explored their life stories, family
      and social aspects emerged as significant influences that associated with
      depression. In a society and culture that relies on and values filial support,
      experiences of being widowed, having poor family support and weak social networks
      appeared to compound and exacerbate depression. CONCLUSIONS: These findings
      highlight that filial support, valued in Chinese culture, is seriously strained
      by the realities of contemporary society. Yet current government policies rely on
      and confirm the role of family support. Findings from this study suggest a need
      for such policies to be reviewed to address the realities of family and social
      support. IMPLICATIONS FOR PRACTICE: The findings have several implications for
      clinical practice. Firstly, the cultural context of Chinese older persons should
      be considered and emphasised in nursing practice. Secondly, the root of
      depression among Chinese older persons is seen to lie in their social, family,
      cultural and day-to-day living issues.

PMID- 23006243
TI  - Latent Class Analysis of college women's Thursday drinking.
AB  - College students drink in consistent patterns over the course of the academic
      semester and year (Beets et al., 2009; Del Boca et al., 2004). However, it is
      unclear if there are naturally occurring groups of female Thursday drinkers who
      display their own unique patterns of drinking across the semester. In a fall
      semester 10-week mixed online- and paper-based study of college female drinking,
      classes of Thursday drinkers were identified using Repeated Measures Latent Class
      Analysis. The 424 participants were recruited via flyers and advertisements in
      the student newspaper. It was determined that three latent classes provided
      optimal fit to the data: 1. Unlikely to report Thursday drinking; 2. Normal
      probability of Thursday drinkers; and 3. High probability of Thursday drinkers.
      The proportion of students within the latent classes differed across academic
      year in school. Seniors were least likely to be in the Unlikely group, and
      juniors and seniors were not in the Normal group. An additional analysis
      indicated that women in a sorority were four times more likely to be in the
      Normal or High groups compared to the Unlikely group. A final set of analyses
      indicated that women who enrolled in Friday morning classes were more likely to
      be in the Unlikely or Normal groups compared to the High group. Results indicated
      that the Unlikely group consumed significantly less alcohol at baseline, had
      lower levels of negative alcohol-related consequences prior to and during the
      study, and drank less on the weekends (Friday and Saturday). Female students who
      report drinking on Thursdays tend to be older, to be part of sororities, to have
      later classes or no classes on Friday, and to experience more negative alcohol
      related consequences. Female students whose "weekends" start early are high-risk
      drinkers and might be targeted for future prevention and intervention efforts.

PMID- 23006244
TI  - How does the Brief CEOA match with self-generated expectancies in mandated
      students?
AB  - Alcohol expectancies, defined as a person's beliefs about the effects of
      drinking, can influence alcohol consumption and help predict problem drinking in
      college students. However, there are concerns that current expectancy measures do
      not adequately capture mandated student expectations about alcohol use. This
      study examined the correspondence of 412 self-generated expectancies from
      mandated students (n=64) to items on the Brief Comprehensive Effects of Alcohol
      (B-CEOA; Ham, Stewart, Norton, & Hope, 2005). Self-generated expectancies were
      reviewed by raters who attempted to match each expectancy with a single B-CEOA
      item based on the qualitative essence of each statement. Most mandated student
      expectancies were not represented by the B-CEOA. All expectancies were then
      classified into 6 categories based on themes and categories from the alcohol
      expectancy literature. Mandated student expectancies emphasized the physiological
      aspects of drinking, whereas the B-CEOA assesses expectancies about intrapersonal
      factors. The findings suggest the B-CEOA may exclude alcohol expectancies that
      are important and relevant to this population. Self-generated alcohol
      expectancies from the target population should be considered when developing or
      administering expectancy questionnaires.

PMID- 23006245
TI  - High-risk cocktails and high-risk sex: examining the relation between alcohol
      mixed with energy drink consumption, sexual behavior, and drug use in college
      students.
AB  - Alcohol mixed with energy drink (AmED) consumption has garnered considerable
      attention in the literature in recent years. Drinking AmED beverages has been
      associated with a host of negative outcomes. The present study sought to examine
      associations between AmED consumption and high-risk sexual behaviors in a sample
      of young adults. Participants (N=704; 59.9% female) completed an online survey
      assessing AmED consumption, other drug use, and sexual behavior. A total of 19.4%
      of the entire sample (and 28.8% of those who reported using alcohol) reported
      consuming AmED. Participants who reported consuming AmED were significantly more
      likely to report marijuana, cocaine, and ecstasy use. Those who reported
      consuming AmED also had increased odds of engaging in high-risk sexual behaviors,
      including unprotected sex, sex while under the influence of drugs, and sex after
      having too much to drink. Relationships between AmED consumption and sexual
      behavior remained significant after accounting for the influence of demographic
      factors and other substance use. Results add to the literature documenting
      negative consequences for AmED consumers, which may include alcohol dependence,
      binge drinking, and the potential for sexually transmitted infections via high
      risk sexual behavior.

PMID- 23006246
TI  - Gender differences in abusers of amphetamine-type stimulants and ketamine in
      southwestern China.
AB  - The objective of this study was to investigate abuse conditions of new-type drugs
      for users who are seeking treatment, gender differences, and differences between
      the amphetamine-type stimulants (ATS) users and mixed amphetamine-type stimulants
      and ketamine (ATS+K) poly-drug users. A retrospective analysis was conducted of
      patients with a final diagnosis of the substance use disorder according to the
      Diagnoses and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) who
      underwent treatment for exposure to new-type drugs at the mental health center of
      the West China Hospital from March 2009 to May 2011. A questionnaire was used to
      collect information about socio-demographics, drug abuse conditions and
      psychiatric co-morbidities. Male subjects were older (p=0.026), had low level
      education (p=0.003), were less previously married (p<0.001), were more likely to
      be employed and to hold higher status jobs (p=0.007); 77.1% of subjects had a
      psychotic disorder, 28.0% of subjects had a mood disorder, 39.7% had an anxiety
      disorder, and 45.0% had a cognitive impairment disorder. More men used
      methamphetamine MA (p<0.001), tobacco (p=0.014) and more than one drug substance
      (p=0.004) compared to women; women were more vulnerable to mood disorders
      (p=0.034) than men. For the males, the ATS+K patients were more likely to use 3,
      4-methylenedioxymethamphetamine MDMA (p<0.001) and develop more psychotic
      disorders (p=0.04) than the ATS patients; for females, the ATS+K patients were
      more likely to use MDMA (p=0.002), alcohol (p=0.014) and develop more cognitive
      impairment disorder (p=0.034). The present study found that the new-type drug
      patients have a high degree of psychiatric morbidities; more men were using MA,
      tobacco and multi-substance and more women patients experience mood disorder in
      the gender differences. For the males, the ATS+K patients were more likely to use
      MDMA (3, 4-methylenedioxymethamphetamine) and develop more psychotic disorders
      than the ATS patients; for females, the ATS+K patients were more likely to use
      MDMA, alcohol and develop more cognitive impairment disorder. These results
      suggested that the psychiatrists should focus on the mood disorder among females,
      psychotic disorders among males who abuse ATS and ketamine, and cognitive
      impairment disorder for the females who abuse ATS and ketamine.

PMID- 23006247
TI  - The relationship between impulsivity, risk-taking propensity and nicotine
      dependence among older adolescent smokers.
AB  - Impulsivity and risk-taking propensity are neurobehavioral traits that reliably
      distinguish between smoking and non-smoking adults. However, how these traits
      relate to smoking quantity and nicotine dependence among older adolescent smokers
      is unclear. The current study examined impulsivity and risk-taking propensity in
      relation to smoking behavior and nicotine dependence among current older
      adolescent smokers (age 16-20 years; N=107). Participants completed the Barratt
      Impulsiveness Scale-11 (BIS-11), the Balloon Analogue Risk Task (BART), and self
      report measures of smoking behavior and nicotine dependence. Results indicated a
      significant positive relationship between nicotine dependence and the Attention
      subscale (beta=.20, t=2.07, p<.05) and the Non-planning subscale (beta=.19,
      t=1.92, p<.06) of the BIS-11. Contrary to expectation, the results also indicated
      a significant negative relationship between performance on the BART and nicotine
      dependence (beta=-.19, t=-2.18, p<.05), such that greater risk-taking propensity
      was associated with less dependence. These data suggest that impulsivity and risk
      taking propensity are related to older adolescent smoking but are separable
      traits with distinguishable associations with nicotine dependence among
      adolescents. These findings support the notion that impulsivity is related to
      heightened nicotine dependence, but suggest that the relationship between risk
      taking propensity and nicotine dependence is more ambiguous and warrants further
      investigation.

PMID- 23006249
TI  - Factors affecting continued use of ceramic water purifiers distributed to tsunami
      affected communities in Sri Lanka.
AB  - OBJECTIVES: There is little information about continued use of point-of-use
      technologies after disaster relief efforts. After the 2004 tsunami, the Red Cross
      distributed ceramic water filters in Sri Lanka. This study determined factors
      associated with filter disuse and evaluate the quality of household drinking
      water. METHODS: A cross-sectional survey of water sources and treatment, filter
      use and household characteristics was administered by in-person oral interview,
      and household water quality was tested. Multivariable logistic regression was
      used to model probability of filter non-use. RESULTS: At the time of survey, 24%
      of households (107/452) did not use filters; the most common reason given was
      breakage (42%). The most common household water sources were taps and wells.
      Wells were used by 45% of filter users and 28% of non-users. Of households with
      taps, 75% had source water Escherichia coli in the lowest World Health
      Organisation risk category (<1/100 ml), vs. only 30% of households reporting
      wells did. Tap households were approximately four times more likely to
      discontinue filter use than well households. CONCLUSION: After 2 years, 24% of
      households were non-users. The main factors were breakage and household water
      source; households with taps were more likely to stop use than households with
      wells. Tap water users also had higher-quality source water, suggesting that
      disuse is not necessarily negative and monitoring of water quality can aid
      decision-making about continued use. To promote continued use, disaster recovery
      filter distribution efforts must be joined with capacity building for long-term
      water monitoring, supply chains and local production.

PMID- 23006248
TI  - Adolescents' fMRI activation to a response inhibition task predicts future
      substance use.
AB  - BACKGROUND: Deficient behavioral regulation may be a risk factor for substance
      use disorders in adolescents. Abnormalities in brain regions critical to
      cognitive control have been linked to more intense and problematic future
      substance use (e.g., Durazzo, Gazdzinski, Mon, & Meyerhoff, 2010; Falk, Berkman,
      Whalen, & Lieberman, 2011; Paulus, Tapert, & Schuckit, 2005). The goal of this
      study was to examine the degree to which brain response to an inhibition task
      measured in mid-adolescence can predict substance use 18 months later. METHOD:
      Adolescents aged 16-19 (N=80) performed a go/no-go response inhibition task
      during fMRI at project baseline, and were followed 18 months later with a
      detailed interview on substance use and dependence symptoms. Participants were 39
      high frequency users and 41 demographically similar low frequency users (458
      versus 2 average lifetime drug use occasions at baseline, respectively). RESULTS:
      Across all subjects, no-go trials produced significant increases in neural
      response in the ventromedial prefrontal cortex and a region including the left
      angular and supramarginal gyri (p(FWE)<.01, cluster threshold >= 30 voxels). Less
      ventromedial prefrontal activation but more left angular gyrus activation
      predicted higher levels of substance use and dependence symptoms in the following
      18 months, particularly for those who were high frequency users in mid
      adolescence (p<.05). CONCLUSIONS: These findings are consistent with studies
      showing that impairments in cognitive control have strong associations with
      substance use. We found a predictive relationship between atypical activation
      patterns at baseline and substance use behavior 18 months later, particularly
      among adolescents with histories of previous heavy use.

PMID- 23006251
TI  - Selective imitation of in-group over out-group members in 14-month-old infants.
AB  - Recent research has shown that infants are more likely to engage with in-group
      over out-group members. However, it is not known whether infants' learning is
      influenced by a model's group membership. This study investigated whether 14
      month-olds (N = 66) selectively imitate and adopt the preferences of in-group
      versus out-group members. Infants watched an adult tell a story either in their
      native language (in-group) or a foreign language (out-group). The adult then
      demonstrated a novel action (imitation task) and chose 1 of 2 objects (preference
      task). Infants did not show selectivity in the preference task, but they imitated
      the in-group model more faithfully than the out-group model. This suggests that
      cultural learning is beginning to be truly cultural by 14 months of age.

PMID- 23006253
TI  - Analytically solvable driven time-dependent two-level quantum systems.
AB  - Analytical solutions to the time-dependent Schrodinger equation describing a
      driven two-level system are invaluable to many areas of physics, but they are
      also extremely rare. Here, we present a simple algorithm that generates an
      unlimited number of exact analytical solutions. We show that a general single
      axis driving term and its corresponding evolution operator are determined by a
      single real function which is constrained only by a certain inequality and
      initial conditions. Any function satisfying these constraints yields an exact
      analytical solution. We demonstrate this method by presenting several new exact
      solutions to the time-dependent Schrodinger equation. Our general method and many
      of the new solutions we present are particularly relevant to qubit control in
      quantum computing applications.

PMID- 23006250
TI  - Self-reported sleep characteristics and mortality in older adults of mexican
      origin: results from the Hispanic established population for the epidemiologic
      study of the elderly.
AB  - OBJECTIVES: To determine how poor sleep affects the health of older ethnic
      minorities. DESIGN: Cross-sectional study involving a population-based survey.
      SETTING: Hispanic Established Population for the Epidemiologic Study of the
      Elderly (H-EPESE) survey conducted in the southwestern United States.
      PARTICIPANTS: Two thousand two hundred fifty-six Mexican-American men and women
      aged 65 and older. MEASUREMENTS: The association between self-reported sleep
      problems and mortality over a 15-year period in a population based sample of
      older Mexican Americans was examined. Using five waves of data (1993-2008) from
      the H-EPESE, Cox proportional hazard models stratified according to sex were used
      to model the risk of death as a function of chronic sleep problems. RESULTS:
      Having any sleeping problems during the last month was associated with greater
      risk of mortality (hazard ratio = 1.14, 95% confidence interval = 1.00-1.29) in
      unadjusted models, although the association was attenuated after accounting for
      covariates. CONCLUSIONS: Similar factors explained the association between sleep
      and mortality in men and women: health behaviors, depressive symptoms, and health
      conditions. These factors are related to stress, and both may lead to poor sleep
      quality. Research is needed to better understand the factors moderating the
      relationship between sleep, mortality, and sex.

PMID- 23006254
TI  - Universal quantum gate set approaching fault-tolerant thresholds with
      superconducting qubits.
AB  - We use quantum process tomography to characterize a full universal set of all
      microwave gates on two superconducting single-frequency single-junction transmon
      qubits. All extracted gate fidelities, including those for Clifford group
      generators, single-qubit pi/4 and pi/8 rotations, and a two-qubit controlled-not,
      exceed 95% (98%), without (with) subtracting state preparation and measurement
      errors. Furthermore, we introduce a process map representation in the Pauli basis
      which is visually efficient and informative. This high-fidelity gate set serves
      as a critical building block towards scalable architectures of superconducting
      qubits for error correction schemes and pushes up on the known limits of quantum
      gate characterization.

PMID- 23006255
TI  - Spectral breaks as a signature of cosmic ray induced turbulence in the Galaxy.
AB  - We show that the complex shape of the cosmic ray (CR) spectrum, as recently
      measured by PAMELA and inferred from Fermi-LAT gamma-ray observations of
      molecular clouds in the Gould belt, can be naturally understood in terms of basic
      plasma astrophysics phenomena. A break from a harder to a softer spectrum at
      rigidity R is approximately equal to 10 GV follows from a transition from
      transport dominated by advection of particles with Alfven waves to a regime where
      diffusion in the turbulence generated by the same CRs is dominant. A second break
      at R is approximately equal to 200 GV happens when the diffusive propagation is
      no longer determined by the self-generated turbulence, but rather by the
      cascading of externally generated turbulence (for instance due to supernova
      bubbles) from large spatial scales to smaller scales where CRs can resonate.
      Implications of this scenario for the cosmic ray spectrum, grammage, and
      anisotropy are discussed.

PMID- 23006256
TI  - Enhancement of dark matter capture by neutron stars in binary systems.
AB  - We study the capture of dark matter particles by neutron stars in close binary
      systems. By performing a direct numerical simulation, we find that there is a
      sizable amplification of the rate of dark matter capture by each of the
      companions. In the case of the binary pulsar PSR J1906+0746 with the orbital
      period of 4 hours the amplification factor is approximately equal to 3.5. This
      amplification can be attributed to the energy loss by dark matter particles
      resulting from their gravitational scattering off moving companions.

PMID- 23006257
TI  - Entanglement of a quantum field with a dispersive medium.
AB  - In this Letter we study the entanglement of a quantum radiation field interacting
      with a dielectric medium. In particular, we describe the quantum mixed state of a
      field interacting with a dielectric through plasma and Drude models and show that
      these generate very different entanglement behavior, as manifested in the
      entanglement entropy of the field. We also present a formula for a "Casimir"
      entanglement entropy, i.e., the distance dependence of the field entropy.
      Finally, we study a toy model of the interaction between two plates. In this
      model, the field entanglement entropy is divergent; however, as in the Casimir
      effect, its distance-dependent part is finite, and the field matter entanglement
      is reduced when the objects are far.

PMID- 23006258
TI  - Light quark mass dependence in heavy quarkonium physics.
AB  - The issue of chiral extrapolations in heavy quarkonium systems is discussed. We
      show that the light quark mass dependence of the properties of heavy quarkonia is
      not always suppressed. For quarkonia close to an open flavor threshold, even a
      nonanalytic chiral extrapolation is needed. Both these nontrivial facts are
      demonstrated to appear in the decay widths of the hindered M1 transitions between
      the first radially excited and ground state P-wave charmonia. The results at a
      pion mass of about 500 MeV could deviate from the value at the physical pion mass
      by a factor of two. Our findings show the necessity of performing chiral
      extrapolations for lattice simulations of heavy quarkonium systems. Furthermore,
      lattice calculations of these transitions would also provide a definite answer to
      the role of coupled-channel effects in heavy quarkonium physics due to virtual
      heavy mesons.

PMID- 23006260
TI  - Charge conservation and the shape of the ridge of two-particle correlations in
      relativistic heavy-ion collisions.
AB  - We demonstrate that, in the framework of the event-by-event hydrodynamics
      followed by statistical hadronization, the proper charge conservation in the
      mechanism of hadron production provides the crucial nonflow component and leads
      to agreement with the two-dimensional two-particle correlation data in relative
      azimuthal angle and pseudorapidity at soft transverse momenta (p(T)<2 GeV). The
      falloff of the same-side ridge in relative pseudorapidity follows from the fact
      that a pair of particles with balanced charges is emitted from the same fluid
      element, whose collective velocity collimates the momenta of the pair. We
      reproduce basic experimental features of the two-dimensional correlation
      function, such as the dependence on the relative charge and centrality, as well
      as the related charge balance functions and the harmonic flow coefficients as
      functions of the relative pseudorapidity.

PMID- 23006261
TI  - Anisotropic optical response of dense quark matter under rotation: compact stars
      as cosmic polarizers.
AB  - Quantum vortices in the color-flavor locked phase of QCD have bosonic degrees of
      freedom, called the orientational zero modes, localized on them. We show that the
      orientational zero modes are electromagnetically charged. As a result, a vortex
      in the color-flavor locked phase nontrivially interacts with photons. We show
      that a lattice of vortices acts as a polarizer of photons with wavelengths larger
      than some critical length.

PMID- 23006262
TI  - Positron attachment to the He doubly excited states.
AB  - The projection method is used to demonstrate the existence of positron attachment
      to three doubly excited states of helium. The e(+)He(2s(2) (1)S(e))deg,
      e(+)He(3s(2) (1)S(e)), and the e(+)He(2s2p (3)P(o)) states have binding energies
      of 0.447, 0.256, and 0.486 eV, respectively. These energies were computed with
      the stochastic variational method and the configuration interaction method. These
      states will exist as resonances in the e(+)-He continuum, and the e(+)He(2s(2)
      (1)S(e)) state could be detectable in the e(+)+He collision spectrum. A resonance
      width of 0.068 eV was computed for the e(+)He(2s(2) (1)S(e)) state by using the
      complex rotation method. The existence of a series of e(+)He(ns(2) (1)S(e))
      resonances associated with the He(ns(2)) double Rydberg series is also predicted,
      and an explicit calculation demonstrating the existence of the e(+)He(3s(2)
      (1)S(e)) state is reported.

PMID- 23006263
TI  - Tunneling facilitated dissociation to H+CO2 in HOCO(-) photodetachment.
AB  - Dissociative photodetachment of HOCO(-) is investigated with both five- and six
      dimensional quantum models on an ab initio based accurate HOCO potential energy
      surface. Three experimentally observed channels, namely, HOCO, H+CO(2), and
      HO+CO, are identified in our theoretical simulations. Since the energy spectrum
      of the initial HOCO species prepared by photodetachment is mostly lower than both
      the HO+CO asymptote and dissociation barrier to H+CO(2), the production of
      H+CO(2) is almost exclusively via tunneling. However, the lowest-lying HOCO
      resonances are extremely long lived (~MUs), which might elude experimental
      measurements through its decay products H+CO(2). Our results are in good
      agreement with almost all experimental data reported by the Continetti group
      using a new cryogenically cooled photoelectron-photofragment coincidence
      apparatus.

PMID- 23006264
TI  - Determination of the surface corrugation amplitude from classical atom
      scattering.
AB  - The energy landscape of an atomic or molecular projectile interacting with a
      surface is often described in terms of a corrugation function that gives the
      classical turning point as a function of position vector parallel to the surface.
      It is shown here that the relative height variation of the corrugation function
      for scattering of atoms under classical conditions can be determined by a
      measurement of the maximum intensity in energy-resolved scattering spectra as a
      function of surface temperature. This is demonstrated by developing a
      semiclassical quantum theory of atomic scattering from corrugated surfaces and
      then extending the theory to the classical limit of large incident energies and
      high surface temperatures. Comparisons of calculations with available data for Ar
      atom scattering determine the corrugation amplitude for a molten In surface to be
      about 29% of the mean interparticle spacing in the bulk liquid.

PMID- 23006265
TI  - Enhanced quantum nonlinearities in a two-mode optomechanical system.
AB  - In cavity optomechanics, nanomechanical motion couples to a localized optical
      mode. The regime of single-photon strong coupling is reached when the optical
      shift induced by a single phonon becomes comparable to the cavity linewidth. We
      consider a setup in this regime comprising two optical modes and one mechanical
      mode. For mechanical frequencies nearly resonant to the optical level splitting,
      we find the photon-phonon and the photon-photon interactions to be significantly
      enhanced. In addition to dispersive phonon detection in a novel regime, this
      offers the prospect of optomechanical photon measurement. We study these quantum
      nondemolition detection processes using both analytical and numerical approaches.

PMID- 23006266
TI  - Efficient channeling of fluorescence photons from single quantum dots into guided
      modes of optical nanofiber.
AB  - We experimentally demonstrate the efficient channeling of fluorescence photons
      from single q dots on optical nanofiber into the guided modes by measuring the
      photon-count rates through the guided and radiation modes simultaneously. We
      obtain the maximum channeling efficiency to be 22.0(+/-4.8)% at a fiber diameter
      of 350 nm for the emission wavelength of 780 nm. The results may open new
      possibilities in quantum information technologies for generating single photons
      into single-mode optical fibers.

PMID- 23006267
TI  - Triple resonant four-wave mixing boosts the yield of continuous coherent vacuum
      ultraviolet generation.
AB  - Efficient continuous-wave four-wave mixing by using three different fundamental
      wavelengths with individual detunings to resonances of the nonlinear medium is
      shown. Up to 6 MUW of vacuum ultraviolet light at 121 nm can be generated, which
      corresponds to an increase of three orders of magnitude in efficiency. This opens
      the field of quantum information processing by Rydberg entanglement of trapped
      ions.

PMID- 23006268
TI  - General linewidth formula for steady-state multimode lasing in arbitrary
      cavities.
AB  - A formula for the laser linewidth of arbitrary cavities in the multimode
      nonlinear regime is derived from a scattering analysis of the solutions to
      semiclassical laser theory. The theory generalizes previous treatments of the
      effects of gain and openness described by the Petermann factor. The linewidth is
      expressed using quantities based on the nonlinear scattering matrix, which can be
      computed from steady-state ab initio laser theory; unlike previous treatments, no
      passive cavity or phenomenological parameters are involved. We find that low
      cavity quality factor, combined with significant dielectric dispersion, can cause
      substantial deviations from the Shawlow-Townes-Petermann theory.

PMID- 23006269
TI  - Self-organized synchronization in decentralized power grids.
AB  - Robust synchronization (phase locking) of power plants and consumers centrally
      underlies the stable operation of electric power grids. Despite current attempts
      to control large-scale networks, even their uncontrolled collective dynamics is
      not fully understood. Here we analyze conditions enabling self-organized
      synchronization in oscillator networks that serve as coarse-scale models for
      power grids, focusing on decentralizing power sources. Intriguingly, we find that
      whereas more decentralized grids become more sensitive to dynamical
      perturbations, they simultaneously become more robust to topological failures.
      Decentralizing power sources may thus facilitate the onset of synchronization in
      modern power grids.

PMID- 23006270
TI  - Time reversal of water waves.
AB  - We present time reversal experiments demonstrating refocusing of gravity
      capillary waves in a water tank cavity. Owing to the reverberating effect of the
      cavity, only a few channels are sufficient to reconstruct the surface wave at the
      point source, even if the absorption is not negligible. Space-time-resolved
      measurements of the waves during the refocusing allow us to quantitatively
      demonstrate that the quality of the refocusing increases linearly with the number
      of reemitting channels. Numerical simulations corresponding to water waves at
      larger scales, with negligible damping, indicate the possibility of very high
      quality refocusing.

PMID- 23006271
TI  - Buckling of viscous filaments of a fluid under compression stresses.
AB  - We study the compression of viscous filaments at constant velocity. If slender
      enough, the filament bends, a viscous analogue of Euler elastic buckling. We
      measure the characteristic time of this viscous buckling and discuss the link
      with the elastic critical compression. We show that the analogy only holds in the
      limit of large capillary numbers. Otherwise capillarity has a stabilizing effect,
      which suppresses buckling.

PMID- 23006272
TI  - Nature of the decrease of the secondary-electron yield by electron bombardment
      and its energy dependence.
AB  - We performed a combined secondary electron yield (SEY) and x-ray photoelectron
      spectroscopy study as a function of the electron dose and energy on a Cu
      technical surface representative of the LHC accelerator walls. The electron
      bombardment is accompanied by a clear chemical modification, indicating an
      increased graphitization as the SEY decreases. The decrease in the SEY is also
      found to depend significantly on the kinetic energy of the primary electrons.
      When low-energy primary electrons are employed (E<=20 eV), the reduction of the
      SEY is slower and smaller in magnitude than when higher-energy electrons are
      used. Consequences of this observation are discussed mainly for their relevance
      on the commissioning scenario for the LHC in operation at CERN (Geneva), but are
      expected to be of interest for other research fields.

PMID- 23006274
TI  - Reduction of ion thermal diffusivity inside a magnetic island in JT-60U tokamak
      plasma.
AB  - A peaked ion temperature profile is observed inside the magnetic island during
      mode locking after the back transition from H mode to L mode in JT-60U. The
      thermal diffusivity evaluated inside the magnetic island is 0.1 m(2)/s, which is
      much smaller than that outside the magnetic island by an order of magnitude. The
      present experiment gives clear evidence that ion heat transport inside a magnetic
      island can bifurcate and the transport level can be suppressed to the very low
      level associated with the strong flow shear at the boundary.

PMID- 23006273
TI  - Low-emittance electron bunches from a laser-plasma accelerator measured using
      single-shot x-ray spectroscopy.
AB  - X-ray spectroscopy is used to obtain single-shot information on electron beam
      emittance in a low-energy-spread 0.5 GeV-class laser-plasma accelerator.
      Measurements of betatron radiation from 2 to 20 keV used a CCD and single-photon
      counting techniques. By matching x-ray spectra to betatron radiation models, the
      electron bunch radius inside the plasma is estimated to be ~0.1 MUm. Combining
      this with simultaneous electron spectra, normalized transverse emittance is
      estimated to be as low as 0.1 mm mrad, consistent with three-dimensional particle
      in-cell simulations. Correlations of the bunch radius with electron beam
      parameters are presented.

PMID- 23006259
TI  - Measurement of the proton-air cross section at ?s=57 TeV with the Pierre Auger
      Observatory.
AB  - We report a measurement of the proton-air cross section for particle production
      at the center-of-mass energy per nucleon of 57 TeV. This is derived from the
      distribution of the depths of shower maxima observed with the Pierre Auger
      Observatory: systematic uncertainties are studied in detail. Analyzing the tail
      of the distribution of the shower maxima, a proton-air cross section of [505+/
      22(stat)(-36)(+28)(syst)] mb is found.

PMID- 23006275
TI  - Direct measurements of the ionization potential depression in a dense plasma.
AB  - We have used the Linac Coherent Light Source to generate solid-density aluminum
      plasmas at temperatures of up to 180 eV. By varying the photon energy of the x
      rays that both create and probe the plasma, and observing the K-alpha
      fluorescence, we can directly measure the position of the K edge of the highly
      charged ions within the system. The results are found to disagree with the
      predictions of the extensively used Stewart-Pyatt model, but are consistent with
      the earlier model of Ecker and Kroll, which predicts significantly greater
      depression of the ionization potential.

PMID- 23006276
TI  - Ionization-grating-induced nonlinear phase accumulation in spectrally resolved
      transient birefringence measurements at 400 nm.
AB  - We report experimental confirmation of the ionization-grating-induced transient
      birefringence predicted by Wahlstrand and Milchberg [Opt. Lett. 36, 3822 (2011)]
      and discuss its impact on the higher-order Kerr effect interpretation by Loriot
      et al. of pump-probe transient birefringence measurements made at 800 nm [Opt.
      Express 17, 13429 (2009)]. Measurement of the transient birefringence in air at
      400 nm shows a negative contribution to the index of refraction at zero delay for
      frequencies within the pump bandwidth, the degenerate case, and no negative
      contribution for frequencies exceeding the pump bandwidth, the nondegenerate
      case. Our findings suggest that a reevaluation of the higher-order Kerr effect
      hypothesis of Loriot et al. is necessary.

PMID- 23006277
TI  - Spontaneous generation of a sheared plasma rotation in a field-reversed theta
      pinch discharge.
AB  - By conducting two-dimensional hybrid simulations of an infinitely long field
      reversed theta-pinch discharge we discover a new type of plasma rotation, which
      rapidly develops at the plasma edge in the ion diamagnetic direction due to the
      self-consistent generation of a Hall-driven radial electric field. This effect is
      different from the previously identified end-shorting and particle-loss
      mechanisms. We also demonstrate flutelike perturbations frequently inferred in
      experiments and show that in the absence of axial contraction effects they may
      quickly alter the toroidal symmetry of the plasma.

PMID- 23006278
TI  - Advantages of mass-imbalanced ultracold fermionic mixtures for approaching
      quantum magnetism in optical lattices.
AB  - We study magnetic phases of two-component mixtures of ultracold fermions with
      repulsive interactions in optical lattices in the presence of hopping imbalance.
      Our analysis is based on dynamical mean-field theory (DMFT) and its real-space
      generalization at finite temperature. We study the temperature dependence of the
      transition into the ordered state as a function of the interaction strength and
      the imbalance parameter in two and three spatial dimensions. We show that below
      the critical temperature for Neel order mass-imbalanced mixtures also exhibit a
      charge-density wave, which provides a directly observable signature of the
      ordered state. For the trapped system, we compare our results obtained by real
      space DMFT to a local-density approximation. We calculate the entropy for a wide
      range of parameters and identify regions, in which mass-imbalanced mixtures could
      have clear advantages over balanced ones for the purpose of obtaining and
      detecting quantum magnetism.

PMID- 23006279
TI  - Stationary growth and unique invariant harmonic measure of cylindrical diffusion
      limited aggregation.
AB  - We prove that the harmonic measure is stationary, unique, and invariant on the
      interface of diffusion limited aggregation (DLA) growing on a cylinder surface.
      We provide a detailed theoretical analysis puzzling together multiscaling,
      multifractality, and conformal invariance, supported by extensive numerical
      simulations of clusters built using conformal mappings and on a lattice. The
      growth properties of the active and frozen zones are clearly elucidated. We show
      that the unique scaling exponent characterizing the stationary growth is the DLA
      fractal dimension.

PMID- 23006280
TI  - Universal monopole scaling near transitions from the Coulomb phase.
AB  - Certain frustrated systems, including spin ice and dimer models, exhibit a
      Coulomb phase at low temperatures, with power-law correlations and fractionalized
      monopole excitations. Transitions out of this phase, at which the effective gauge
      theory becomes confining, provide examples of unconventional criticality. This
      Letter studies the behavior at nonzero monopole density near such transitions,
      using scaling theory to arrive at universal expressions for the crossover
      phenomena. For a particular transition in spin ice, quantitative predictions are
      made by mapping to the XY model and confirmed using Monte Carlo simulations.

PMID- 23006281
TI  - Exploring mesoscopic physics of vacancy-ordered systems through atomic scale
      observations of topological defects.
AB  - Vacancy-ordered transition metal oxides have multiple similarities to classical
      ferroic systems including ferroelectrics and ferroelastics. The expansion
      coefficients for corresponding Ginzburg-Landau-type free energies are readily
      accessible from bulk phase diagrams. Here, we demonstrate that the gradient and
      interfacial terms can quantitatively be determined from the atomically resolved
      scanning transmission electron microscopy data of the topological defects and
      interfaces in model lanthanum-strontium cobaltite. With this knowledge, the
      interplay between ordering, chemical composition, and mechanical effects at
      domain walls, interfaces and structural defects can be analyzed.

PMID- 23006282
TI  - Thermophobicity of liquids: heats of transport in mixtures as pure component
      properties.
AB  - We have measured the Soret coefficients of 41 out of 45 possible equimolar binary
      mixtures of 10 different organic solvents and found an additive rule for the
      heats of transport. These can, except for an undetermined offset, uniquely be
      assigned to the pure components. Based on their heats of transport, the fluids
      can be arranged according to their thermophobicity, similar to the standard
      electrode potential. A qualitative explanation of this unexpected additivity is
      based on the work of Morozov [Phys. Rev. E 79, 031204 (2009)].

PMID- 23006283
TI  - Ring state for single transition metal atoms on boron nitride on Rh(111).
AB  - The low-temperature adsorption of isolated transition metal adatoms (Mn, Co, and
      Fe) onto hexagonal boron nitride monolayers on Rh(111) creates a bistable
      adsorption complex. The first state considerably weakens the hexagonal boron
      nitride- (h-BN-) substrate bond for 60 BN unit cells, leading to a highly
      symmetric ring in STM images, while the second state is imaged as a conventional
      adatom and leaves the BN-substrate interaction intact. We demonstrate reversible
      switching between the two states and, thus, controlled pinning and unpinning of
      the h-BN layer from the metal substrate. I(z) and d lnI/dz curves are used to
      reveal the BN deformation in the ring state.

PMID- 23006284
TI  - Nonintrusive optical visualization of surface nanobubbles.
AB  - Individual surface nanobubbles are visualized with nonintrusive optical
      interference-enhanced reflection microscopy, demonstrating that their formation
      is not a consequence of the hitherto used intrusive atomic force microscopy
      technique. We then use this new and fast technique to demonstrate that surface
      nanobubbles form in less than a few seconds after ethanol-water exchange, which
      is the standard procedure for their preparation, and examine how they react to
      temperature variations.

PMID- 23006285
TI  - Noncoalescence of sessile drops from different but miscible liquids: hydrodynamic
      analysis of the twin drop contour as a self-stabilizing traveling wave.
AB  - Capillarity always favors drop fusion. Nevertheless, sessile drops from different
      but completely miscible liquids often do not fuse instantaneously upon contact.
      Rather, intermediate noncoalescence is observed. Two separate drop bodies,
      connected by a thin liquid neck, move over the substrate. Supported by new
      experimental data, a thin film hydrodynamic analysis of this state is presented.
      Presumably advective and diffusive volume fluxes in the neck region establish a
      localized and temporarily stable surface tension gradient. This induces a local
      surface (Marangoni) flow that stabilizes a traveling wave, i.e., the observed
      moving twin drop configuration. The theoretical predictions are in excellent
      agreement with the experimental findings.

PMID- 23006286
TI  - Correlation effects on 3D topological phases: from bulk to boundary.
AB  - Topological phases of quantum matter defy characterization by conventional order
      parameters but can exhibit a quantized electromagnetic response and/or protected
      surface states. We examine such phenomena in a model for three-dimensional
      correlated complex oxides, the pyrochlore iridates. The model realizes
      interacting topological insulators, with and without time-reversal symmetry, and
      topological Weyl semimetals. We use cellular dynamical mean-field theory, a
      method that incorporates quantum many-body effects and allows us to evaluate the
      magnetoelectric topological response coefficient in correlated systems. This
      invariant is used to unravel the presence of an interacting axion insulator
      absent within a simple mean-field study. We corroborate our bulk results by
      studying the evolution of the topological boundary states in the presence of
      interactions. Consequences for experiments and for the search for correlated
      materials with symmetry-protected topological order are given.

PMID- 23006287
TI  - Chemical composition tuning of the anomalous Hall effect in isoelectronic
      L10FePd(1-x)Pt(x) alloy films.
AB  - The anomalous Hall effect (AHE) in L1(0)FePd(1-x)Pt(x) alloy films is studied
      both experimentally and theoretically. We find that the intrinsic contribution
      (sigma(AH)(int)) to the AHE can be significantly increased, whereas the extrinsic
      side-jump contribution (sigma(AH)(sj)) can be continuously reduced from being
      slightly larger than sigma(AH)(int) in L1(0) FePd to being much smaller than
      sigma(AH)(int) in L1(0) FePt, by increasing the Pt composition x. We show that
      this chemical composition tuning of the intrinsic contribution is afforded by the
      stronger spin-orbit coupling strength on the Pd/Pt site when the lighter Pd atoms
      are replaced by the heavier Pt atoms. Our results provide a means of manipulating
      the competing AHE mechanisms in ferromagnetic alloys for fully understanding the
      AHE and also for technological applications of ferromagnetic alloys.

PMID- 23006288
TI  - Entanglement probe of two-impurity Kondo physics in a spin chain.
AB  - We propose that real-space properties of the two-impurity Kondo model can be
      obtained from an effective spin model where two single-impurity Kondo spin chains
      are joined via an Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction between the
      two impurity spins. We then use a density matrix renormalization group approach,
      valid in all ranges of parameters, to study its features using two complementary
      quantum-entanglement measures, the negativity and the von Neumann entropy. This
      nonperturbative approach enables us to uncover the precise dependence of the
      spatial extent xi(K) of the Kondo screening cloud with the Kondo and RKKY
      couplings. Our results reveal an exponential suppression of the Kondo temperature
      T(K)~1/xi(K) with the size of the effective impurity spin in the limit of large
      ferromagnetic RKKY coupling, a striking display of "Kondo resonance narrowing" in
      the two-impurity Kondo model. We also show how the antiferromagnetic RKKY
      interaction produces an effective decoupling of the impurities from the bulk
      already for intermediate strengths of this interaction, and, furthermore, exhibit
      how the non-Fermi liquid quantum critical point is signaled in the quantum
      entanglement between various parts of the system.

PMID- 23006289
TI  - High-energy anomaly in the band dispersion of the ruthenate superconductor.
AB  - We reveal a "high-energy anomaly" (HEA) in the band dispersion of the
      unconventional ruthenate superconductor Sr2RuO4, by means of high-resolution
      angle-resolved photoemission spectroscopy (ARPES) with tunable energy and
      polarization of incident photons. This observation provides another class of
      correlated materials exhibiting this anomaly beyond high-T(c) cuprates. We
      demonstrate that two distinct types of band renormalization associated with and
      without the HEA occur as a natural consequence of the energetics in the bandwidth
      and the energy scale of the HEA. Our results are well reproduced by a simple
      analytical form of the self-energy based on the Fermi-liquid theory, indicating
      that the HEA exists at a characteristic energy scale of the multielectron
      excitations. We propose that the HEA universally emerges if the systems have such
      a characteristic energy scale inside of the bandwidth.

PMID- 23006290
TI  - Controlling shot noise in double-barrier magnetic tunnel junctions.
AB  - We demonstrate that shot noise in Fe/MgO/Fe/MgO/Fe double-barrier magnetic tunnel
      junctions is determined by the relative magnetic configuration of the junction
      and also by the asymmetry of the barriers. The proposed theoretical model, based
      on sequential tunneling through the system and including spin relaxation,
      successfully accounts for the experimental observations for bias voltages below
      0.5 V, where the influence of quantum well states is negligible. A weak
      enhancement of conductance and shot noise, observed at some voltages (especially
      above 0.5 V), indicates the formation of quantum well states in the middle
      magnetic layer. The observed results open up new perspectives for a reliable
      magnetic control of the most fundamental noise in spintronic structures.

PMID- 23006291
TI  - Confined doping on a metallic atomic chain structure.
AB  - On Si(111)-(5*2)-Au it is shown that metallic sections of quantum wires between
      two doping adatoms establish a local electronic structure which is primarily
      defined by the section length. Such confined doping is a direct consequence of
      reduced dimensionality and is not observed in higher dimensions. Within a chain
      segment, the effect of a spatially independent charge-carrier concentration is
      superimposed by a Coulomb-like interaction due to the positively charged dopants.
      This offers a natural explanation for the relatively broad photoemission features
      and the complex appearance in scanning tunneling microscopy and spectroscopy
      images.

PMID- 23006292
TI  - Interaction-induced topological insulator states in strained graphene.
AB  - The electronic properties of graphene can be manipulated via mechanical
      deformations, which opens prospects for both studying the Dirac fermions in new
      regimes and for new device applications. Certain natural configurations of strain
      generate large nearly uniform pseudomagnetic fields, which have opposite signs in
      the two valleys, and give rise to flat spin- and valley-degenerate pseudo-Landau
      levels (PLLs). Here we consider the effect of the Coulomb interactions in
      strained graphene with a uniform pseudomagnetic field. We show that the spin or
      valley degeneracies of the PLLs get lifted by the interactions, giving rise to
      topological insulator states. In particular, when a nonzero PLL is quarter or
      three-quarter filled, an anomalous quantum Hall state spontaneously breaking time
      reversal symmetry emerges. At half-filled PLLs, a weak spin-orbital interaction
      stabilizes the time-reversal-symmetric quantum spin-Hall state. These many-body
      states are characterized by the quantized conductance and persist to a high
      temperature scale set by the Coulomb interactions, which we estimate to be a few
      hundreds Kelvin at moderate strain values. At fractional fillings, fractional
      quantum Hall states breaking valley symmetry emerge. These results suggest a new
      route to realizing robust topological states in mesoscopic graphene.

PMID- 23006293
TI  - Manifestation of topological protection in transport properties of epitaxial
      Bi2Se3 thin films.
AB  - The massless Dirac fermions residing on the surface of three-dimensional
      topological insulators are protected from backscattering and cannot be localized
      by disorder, but such protection can be lifted in ultrathin films when the three
      dimensionality is lost. By measuring the Shubnikov-de Haas oscillations in a
      series of high-quality Bi2Se3 thin films, we revealed a systematic evolution of
      the surface conductance as a function of thickness and found a striking
      manifestation of the topological protection: The metallic surface transport
      abruptly diminishes below the critical thickness of ~6 nm, at which an energy gap
      opens in the surface state and the Dirac fermions become massive. At the same
      time, the weak antilocalization behavior is found to weaken in the gapped phase
      due to the loss of pi Berry phase.

PMID- 23006294
TI  - Flux noise probed with real time qubit tomography in a Josephson phase qubit.
AB  - We measure the dependence of qubit phase coherence and flux noise on inductor
      loop geometry. While wider inductor traces change neither the flux noise power
      spectrum nor the qubit dephasing time, increased inductance leads to a
      simultaneous increase in both. Using our new tomographic protocol for measuring
      low frequency flux noise, we make a direct comparison between the flux noise
      spectrum and qubit phase decay, finding agreement within 10% of theory.

PMID- 23006295
TI  - Absorption of heat into a superconductor-normal metal-superconductor junction
      from a fluctuating environment.
AB  - We study a diffusive superconductor-normal-metal-superconductor junction in an
      environment with intrinsic incoherent fluctuations which couple to the junction
      through an electromagnetic field. When the temperature of the junction differs
      from that of the environment, this coupling leads to an energy transfer between
      the two systems, taking the junction out of equilibrium. We describe this effect
      in the linear response regime and show that the change in the supercurrent
      induced by this coupling leads to qualitative changes in the current-phase
      relation and, for a certain range of parameters, an increase in the critical
      current of the junction. In addition to normal metals, similar effects can be
      expected also in other conducting weak links.

PMID- 23006296
TI  - ns-Tc correlations in granular superconductors.
AB  - Following a short discussion of the granular model for an inhomogeneous
      superconductor, we review the Uemura and Homes correlations and show how both
      follow in two limits of a simple granular superconductor model. Definite
      expressions are given for the almost universal coefficients appearing in these
      relationships in terms of known constants.

PMID- 23006297
TI  - Dynamical particle-hole asymmetry in high-temperature cuprate superconductors.
AB  - Motivated by the form of recent theoretical results, a quantitative test for an
      important dynamical particle-hole asymmetry of the electron spectral function at
      low energies and long wavelengths is proposed. The test requires the
      decomposition of the angle resolved photo emission intensity, after a specific
      Fermi symmetrization, into odd and even parts to obtain its ratio R. A large
      magnitude R is implied in recent theoretical fits at optimal doping around the
      chemical potential, and I propose that this large asymmetry needs to be checked
      more directly and thoroughly. This processing requires a slightly higher
      precision determination of the Fermi momentum relative to current availability.

PMID- 23006298
TI  - Nature of the spin-liquid ground state of the S=1/2 Heisenberg model on the
      kagome lattice.
AB  - We perform a density-matrix renormalization group (DMRG) study of the S=1/2
      Heisenberg antiferromagnet on the kagome lattice to identify the conjectured spin
      liquid ground state. Exploiting SU(2) spin symmetry, which allows us to keep up
      to 16,000 DMRG states, we consider cylinders with circumferences up to 17 lattice
      spacings and find a spin liquid ground state with an estimated per site energy of
      -0.4386(5), a spin gap of 0.13(1), very short-range decay in spin, dimer and
      chiral correlation functions, and finite topological entanglement gamma
      consistent with gamma=log(2)2, ruling out gapless, chiral, or nontopological spin
      liquids in favor of a topological spin liquid of quantum dimension 2, with strong
      evidence for a gapped topological Z(2) spin liquid.

PMID- 23006299
TI  - Hidden order in URu2Si2 unveiled.
AB  - We report on measurements, by polarized neutron elastic scattering, of the
      magnetization distribution induced in a single crystal of URu2Si2 under a
      magnetic field applied along the tetragonal c axis. A subtle change in this
      distribution, revealed by maximum entropy analysis of the data, is found when the
      temperature is decreased to the range of the hidden order. An analysis in terms
      of U(4+) ionic states reveals that this change is a fingerprint of a freezing of
      rank 5 multipoles, i.e., dotriacontapoles.

PMID- 23006300
TI  - Atomistic molecular dynamic simulations of multiferroics.
AB  - A first-principles-based approach is developed to simulate dynamical properties,
      including complex permittivity and permeability in the GHz-THz range, of
      multiferroics at finite temperatures. It includes both structural degrees of
      freedom and magnetic moments as dynamic variables in Newtonian and Landau
      Lifshitz-Gilbert (LLG) equations within molecular dynamics, respectively, with
      the couplings between these variables being incorporated. The use of a damping
      coefficient and of the fluctuation field in the LLG equations is required to
      obtain equilibrated magnetic properties at any temperature. No electromagnon is
      found in the spin-canted structure of BiFeO3. On the other hand, two magnons with
      very different frequencies are predicted via the use of this method. The smallest
      in-frequency magnon corresponds to oscillations of the weak ferromagnetic vector
      in the basal plane being perpendicular to the polarization while the second
      magnon corresponds to magnetic dipoles going in and out of this basal plane. The
      large value of the frequency of this second magnon is caused by static couplings
      between magnetic dipoles with electric dipoles and oxygen octahedra tiltings.

PMID- 23006301
TI  - Formation of magnetic microphases in Ca3Co2O6.
AB  - We study a frustrated quantum Ising model relevant for Ca3Co2O6 that consists of
      a triangular lattice of weakly coupled ferromagnetic chains. According to our
      quantum Monte Carlo simulations, the chains become ferromagnetic and form a three
      sublattice "up-up-down" structure for T<=T(CI). In contrast, long-wavelength spin
      density-wave microphases are stabilized along the chains for T(CI)<T<T(c). Our
      mean field solutions reveal a quasicontinuous temperature dependence of the
      modulation wavelength, implying the existence of metastable states that explain
      the very slow dynamics observed in Ca3Co2O6. We also discuss implications of
      microphases for the related multiferroic compounds Ca3CoMnO6 and Lu2MnCoO6.

PMID- 23006302
TI  - magnetic dispersion and anisotropy in multiferroic BiFeO3.
AB  - We have determined the full magnetic dispersion relations of multiferroic BiFeO3.
      In particular, two excitation gaps originating from magnetic anisotropies have
      been clearly observed. The direct observation of the gaps enables us to
      accurately determine the Dzyaloshinskii-Moriya (DM) interaction and the single
      ion anisotropy. The DM interaction supports a sizable magnetoelectric coupling in
      this compound.

PMID- 23006303
TI  - Observation and differentiation of unique high-Q optical resonances near zero
      wave vector in macroscopic photonic crystal slabs.
AB  - We demonstrate and distinguish experimentally the existence of a special type of
      Fano resonances at k~0 in a macroscopic two-dimensional photonic crystal slab. We
      fabricate a square lattice array of holes in a silicon nitride layer and perform
      an angular resolved spectral analysis of the various Fano resonances. We
      elucidate their radiation behavior using temporal coupled-mode theory and
      symmetry considerations. The unique simplicity of this system whereby an
      ultralong lifetime delocalized electromagnetic field can exist above the surface
      and consequently easily interact with added matter, provides exciting new
      opportunities for the study of light and matter interaction.

PMID- 23006304
TI  - Ferroelectric PbTiO3/SrRuO3 superlattices with broken inversion symmetry.
AB  - We have fabricated PbTiO3/SrRuO3 superlattices with ultrathin SrRuO3 layers.
      Because of the superlattice geometry, the samples show a large anisotropy in
      their electrical resistivity, which can be controlled by changing the thickness
      of the PbTiO3 layers. Therefore, along the ferroelectric direction, SrRuO3 layers
      can act as dielectric, rather than metallic, elements. We show that, by reducing
      the concentration of PbTiO3, an increasingly important effect of polarization
      asymmetry due to compositional inversion symmetry breaking occurs. The results
      are significant as they represent a new class of ferroelectric superlattices,
      with a rich and complex phase diagram. By expanding our set of materials we are
      able to introduce new behaviors that can only occur when one of the materials is
      not a perovskite titanate. Here, compositional inversion symmetry breaking in
      bicolor superlattices, due to the combined variation of A and B site ions within
      the superlattice, is demonstrated using a combination of experimental
      measurements and first principles density functional theory.

PMID- 23006305
TI  - Partial collapse and reswelling of a polymer in the critical demixing region of
      good solvents.
AB  - Using small-angle neutron scattering, we explored the conformational behavior of
      a polymer in a mixture of good solvents near their critical demixing temperature
      T(C). Experiments at full and zero average neutron contrast were used to study
      the correlation length of concentration fluctuations xi and the radius of
      gyration R(g) of individual polymer coils as a function of temperature T. The
      results confirm a theoretically predicted partial collapse followed by reswelling
      of polymer coils to the original dimensions as T->T(C). Reswelling begins when xi
      becomes comparable to the R(g) of the polymer.

PMID- 23006306
TI  - Breaking arches with vibrations: the role of defects.
AB  - We present experimental and numerical results regarding the stability of arches
      against external vibrations. Two-dimensional strings of mutually stabilizing
      grains are geometrically analyzed and subsequently submitted to a periodic
      forcing at fixed frequency and increasing amplitude. The main factor that
      determines the granular arch resistance against vibrations is the maximum angle
      among those formed between any particle of the arch and its two neighbors: the
      higher the maximum angle is, the easier it is to break the arch. On the basis of
      an analysis of the forces, a simple explanation is given for this dependence.
      From this, interesting information can be extracted about the expected magnitudes
      of normal forces and friction coefficients of the particles composing the arches.

PMID- 23006307
TI  - Osmotic Pressure Induced Coupling between Cooperativity and Stability of a Helix
      Coil Transition.
AB  - Most helix-coil transition theories can be characterized by three parameters:
      energetic, describing the (free) energy cost of forming a helical state in one
      repeating unit; entropic, accounting for the decrease of entropy due to formation
      of the helical state; and geometric, indicating how many repeating units are
      affected by the formation of one helical state. Depending on their effect on the
      helix-coil transition, solvents or cosolutes can be classified with respect to
      their action on these parameters. Solvent interactions that alter the entropic
      cost of helix formation by their osmotic action can affect both the stability
      (transition temperature) and the cooperativity (transition interval) of the helix
      coil transition. Consistent inclusion of osmotic pressure effects in a
      description of helix-coil transition, for poly(L-glutamic acid) in solution with
      polyethylene glycol, can offer an explanation of the experimentally observed
      linear dependence of transition temperature on osmotic pressure as well as the
      concurrent changes in the cooperativity of the transition.

PMID- 23006309
TI  - Breath figures: nucleation, growth, coalescence, and the size distribution of
      droplets.
AB  - The analysis of the size distribution of droplets condensing on a substrate
      (breath figures) is a test ground for scaling theories. Here, we show that a
      faithful description of these distributions must explicitly deal with the growth
      mechanisms of the droplets. This finding establishes a gateway connecting
      nucleation and growth of the smallest droplets on surfaces to gross features of
      the evolution of the droplet size distribution.

PMID- 23006308
TI  - Transition path times for nucleic Acid folding determined from energy-landscape
      analysis of single-molecule trajectories.
AB  - The duration of structural transitions in biopolymers is only a fraction of the
      time spent searching diffusively over the configurational energy landscape. We
      found the transition time, tau(TP), and the diffusion constant, D, for DNA and
      RNA folding using energy landscapes obtained from single-molecule trajectories
      under tension in optical traps. DNA hairpins, RNA pseudoknots, and a riboswitch
      all had tau(TP)~10 MUs and D~10(-13-14) m(2)/s, despite widely differing
      unfolding rates. These results show how energy-landscape analysis can be
      harnessed to characterize brief but critical events during folding reactions.

PMID- 23006310
TI  - Locating the source of diffusion in large-scale networks.
AB  - How can we localize the source of diffusion in a complex network? Because of the
      tremendous size of many real networks-such as the internet or the human social
      graph-it is usually unfeasible to observe the state of all nodes in a network. We
      show that it is fundamentally possible to estimate the location of the source
      from measurements collected by sparsely placed observers. We present a strategy
      that is optimal for arbitrary trees, achieving maximum probability of correct
      localization. We describe efficient implementations with complexity O(N(alpha)),
      where alpha=1 for arbitrary trees and alpha=3 for arbitrary graphs. In the
      context of several case studies, we determine how localization accuracy is
      affected by various system parameters, including the structure of the network,
      the density of observers, and the number of observed cascades.

PMID- 23006311
TI  - Comment on "Global positioning system test of the local position invariance of
      Planck's constant".

PMID- 23006313
TI  - Protein kinase C activation stimulates mesenchymal stem cell adhesion through
      activation of focal adhesion kinase.
AB  - Emerging evidence suggests that cell therapy with mesenchymal stem cells (MSCs)
      has beneficial effects on the injured heart. However, the decreased survival
      and/or adhesion of MSCs under ischemic conditions limits the application of cell
      transplantation as a therapeutic modality. We investigated a potential method of
      increasing the adhesion ability of MSCs to improve their efficacy in the ischemic
      heart. Treatment of MSCs with PKC activator, phorbol 12-myristate 13-acetate
      (PMA), increased cell adhesion and spreading in a dose-dependent method and
      significantly decreased detachment. When MSCs were treated with PKC inhibitor,
      that is, rottlerin, adhesion of MSCs was slightly diminished, and detachment was
      also decreased compared to the treatment with PMA. MSCs treated with both PMA and
      rottlerin behaved similarly to normal controls. In 3D matrix cardio gel,
      treatment with PMA increased the number of MSCs compared to the control group and
      MSCs treated with rottlerin. Expressions of focal adhesion kinase, cytoskeleton
      associated proteins, and integrin subunits were clearly demonstrated in PMA
      treated MSCs by immunoblotting and/or immunocytochemistry. The effect of PKC
      activator treatment on MSCs was validated in vivo. Following injection into rat
      hearts, the PMA-treated MSCs exhibited significantly higher retention in
      infarcted myocardium compared to the MSC group. Infarct size, fibrosis area, and
      apoptotic cells were reduced, and cardiac function was improved in rat hearts
      injected with PMA-treated MSCs compared to sham and/or MSC-implanted group. These
      results indicate that PKC activator is a potential target for niche manipulation
      to enhance adhesion of MSCs for cardiac regeneration.

PMID- 23006314
TI  - An efficient procedure for protein extraction from formalin-fixed, paraffin
      embedded tissues for reverse phase protein arrays.
AB  - INTRODUCTION: Protein extraction from formalin-fixed paraffin-embedded (FFPE)
      tissues is challenging due to extensive molecular crosslinking that occurs upon
      formalin fixation. Reverse-phase protein array (RPPA) is a high-throughput
      technology, which can detect changes in protein levels and protein functionality
      in numerous tissue and cell sources. It has been used to evaluate protein
      expression mainly in frozen preparations or FFPE-based studies of limited scope.
      Reproducibility and reliability of the technique in FFPE samples has not yet been
      demonstrated extensively. We developed and optimized an efficient and
      reproducible procedure for extraction of proteins from FFPE cells and xenografts,
      and then applied the method to FFPE patient tissues and evaluated its performance
      on RPPA. RESULTS: Fresh frozen and FFPE preparations from cell lines, xenografts
      and breast cancer and renal tissues were included in the study. Serial FFPE cell
      or xenograft sections were deparaffinized and extracted by six different protein
      extraction protocols. The yield and level of protein degradation were evaluated
      by SDS-PAGE and Western Blots. The most efficient protocol was used to prepare
      protein lysates from breast cancer and renal tissues, which were subsequently
      subjected to RPPA. Reproducibility was evaluated and Spearman correlation was
      calculated between matching fresh frozen and FFPE samples.The most effective
      approach from six protein extraction protocols tested enabled efficient
      extraction of immunoreactive protein from cell line, breast cancer and renal
      tissue sample sets. 85% of the total of 169 markers tested on RPPA demonstrated
      significant correlation between FFPE and frozen preparations (p < 0.05) in at
      least one cell or tissue type, with only 23 markers common in all three sample
      sets. In addition, FFPE preparations yielded biologically meaningful observations
      related to pathway signaling status in cell lines, and classification of renal
      tissues. CONCLUSIONS: With optimized protein extraction methods, FFPE tissues can
      be a valuable source in generating reproducible and biologically relevant
      proteomic profiles using RPPA, with specific marker performance varying according
      to tissue type.

PMID- 23006315
TI  - Seed dimorphism, nutrients and salinity differentially affect seed traits of the
      desert halophyte Suaeda aralocaspica via multiple maternal effects.
AB  - BACKGROUND: Maternal effects may influence a range of seed traits simultaneously
      and are likely to be context-dependent. Disentangling the interactions of plant
      phenotype and growth environment on various seed traits is important for
      understanding regeneration and establishment of species in natural environments.
      Here, we used the seed-dimorphic plant Suaeda aralocaspica to test the hypothesis
      that seed traits are regulated by multiple maternal effects. RESULTS: Plants
      grown from brown seeds had a higher brown:black seed ratio than plants from black
      seeds, and germination percentage of brown seeds was higher than that of black
      seeds under all conditions tested. However, the coefficient of variation (CV) for
      size of black seeds was higher than that of brown seeds. Seeds had the smallest
      CV at low nutrient and high salinity for plants from brown seeds and at low
      nutrient and low salinity for plants from black seeds. Low levels of nutrients
      increased size and germinability of black seeds but did not change the seed morph
      ratio or size and germinability of brown seeds. High levels of salinity decreased
      seed size but did not change the seed morph ratio. Seeds from high-salinity
      maternal plants had a higher germination percentage regardless of level of
      germination salinity. CONCLUSIONS: Our study supports the multiple maternal
      effects hypothesis. Seed dimorphism, nutrient and salinity interacted in
      determining a range of seed traits of S. aralocaspica via bet-hedging and
      anticipatory maternal effects. This study highlights the importance of examining
      different maternal factors and various offspring traits in studies that estimate
      maternal effects on regeneration.

PMID- 23006317
TI  - Josephson current through interacting double quantum dots with spin-orbit
      coupling.
AB  - We study the effect of Rashba spin-orbit interaction on the Josephson current
      through a double quantum dot in the presence of Coulomb repulsion. In particular,
      we describe the characteristic effects on the magnetic field-induced singlet
      triplet transition in the molecular regime. Exploring the whole parameter space,
      we analyze the effects of the device asymmetry, the orientation of the applied
      magnetic field with respect to the spin-orbit interaction, and finite
      temperatures. We find that at finite temperatures the orthogonal component of the
      spin-orbit interaction exhibits a similar effect to the Coulomb interaction
      inducing the occurrence of a pi-phase at particle-hole symmetry. This provides a
      new route to the experimental observability of the pi-phase in multi-level
      quantum dots.

PMID- 23006316
TI  - Nonurgent patients in emergency departments: rational or irresponsible consumers?
      Perceptions of professionals and patients.
AB  - BACKGROUND: For several decades, overcrowding in emergency departments (EDs) has
      been intensifying due to the increased number of patients seeking care in EDs.
      Demand growth is partly due to misuse of EDs by patients who seek care for
      nonurgent problems. This study explores the reasons why people with nonurgent
      complaints choose to come to EDs, and how ED health professionals perceive the
      phenomenon of "nonurgency". RESULTS: Semi-structured interviews were conducted in
      10 EDs with 87 nonurgent patients and 34 health professionals. Interviews of
      patients revealed three themes: (1) fulfilled health care needs, (2) barriers to
      primary care providers (PCPs), and (3) convenience. Patients chose EDs as
      discerning health consumers: they preferred EDs because they had difficulties
      obtaining a rapid appointment. Access to technical facilities in EDs spares the
      patient from being overwhelmed with appointments with various specialists. Four
      themes were identified from the interviews of health professionals: (1) the
      problem of defining a nonurgent visit, (2) explanations for patients' use of EDs
      for nonurgent complaints, (3) consequences of nonurgent visits, and (4) solutions
      to counter this tendency. CONCLUSIONS: Studies on the underlying reasons patients
      opt for the ED, as well as on their decision-making process, are lacking. The
      present study highlighted discrepancies between the perceptions of ED patients
      and those of health professionals, with a special focus on patient behaviour. To
      explain the use of ED, health professionals based themselves on the acuity and
      urgency of medical problems, while patients focused on rational reasons to
      initiate care in the ED (accessibility to health care resources, and the context
      in which the medical problem occurred). In spite of some limitations due to the
      slightly outdated nature of our data, as well as the difficulty of categorizing
      nonurgent situations, our findings show the importance of conducting a detailed
      analysis of the demand for health care. Understanding it is crucial, as it is the
      main determining factor in the utilization of health care resources, and provides
      promising insights into the phenomenon of ED usage increase. For reforms to be
      successful, the process of decision-making for unscheduled patients will have to
      be thoroughly investigated.

PMID- 23006318
TI  - Relationship between BDNF expression in major striatal afferents, striatum
      morphology and motor behavior in the R6/2 mouse model of Huntington's disease.
AB  - Patients with Huntington's disease (HD) and transgenic mouse models of HD show
      neuronal loss in the striatum as a major feature, which contributes to cognitive
      and motor manifestations. Reduced expression of the neurotrophin brain-derived
      neurotrophic factor (BDNF) in striatal afferents may play a role in neuronal
      loss. How progressive loss of BDNF expression in different cortical or
      subcortical afferents contributes to striatal atrophy and behavioral dysfunction
      in HD is not known, and may best be determined in animal models. We compared age
      dependent alterations of BDNF mRNA expression in major striatal afferents from
      the cerebral cortex, thalamus and midbrain in the R6/2 transgenic mouse model of
      HD. Corresponding changes in striatal morphology were quantified using unbiased
      stereology. Changes in motor behavior were measured using an open field, grip
      strength monitor, limb clasping and a rotarod apparatus. BDNF expression in
      cortical limbic and midbrain striatal afferents is reduced by age 4 weeks, prior
      to onset of motor abnormalities. BDNF expression in motor cortex and thalamic
      afferents is reduced by 6 weeks, coinciding with early motor dysfunction and
      reduced striatum volume. BDNF loss in afferents progresses until death at 13-15
      weeks, correlating with progressive striatal neuronal loss and motor
      abnormalities. Mutant huntingtin protein expression in R6/2 mice results in
      progressive loss of BDNF in both cortical and subcortical striatal afferents.
      BDNF loss in limbic and dopaminergic striatal inputs may contribute to
      cognitive/psychiatric dysfunction in HD. Subsequent BDNF loss in cortical motor
      and thalamic afferents may accelerate striatal degeneration, resulting in
      progressive involuntary movements.

PMID- 23006320
TI  - During critical illness the gut does not pass the acid test.
AB  - The composition and function of intestinal microflora are emerging as integral to
      both health and disease. During critical illness the normal microbiota are
      rapidly replaced by pathogenic species as a result of both the physiologic stress
      itself and the use of antibiotics. In this report, the authors use fecal pH as a
      surrogate marker to determine the predictive value of the functional output of
      the intestinal microflora during critical illness. Fecal pH appears to be highly
      predictive of outcome from critical illness, and may reflect the output of key
      organic acids such as the short-chain fatty acids, lactic acid, and other
      important products of the gut microflora. 

PMID- 23006319
TI  - Increased expression of Golgi phosphoprotein-3 is associated with tumor
      aggressiveness and poor prognosis of prostate cancer.
AB  - BACKGROUND: To investigate the expression of Golgi phosphoprotein-3 (GOLPH3) in
      prostate cancer and determine its prognostic value. METHODS: Immunohistochemical
      staining for GOLPH3 was performed on tissue microarrays of 342 prostate patients.
      The correlation between GOLPH3 expression with its clinicopathologic factors was
      also analyzed in order to determine its prognostic significance. RESULTS: GOLPH3
      expression of normal prostate tissues, benign prostate hyperplasia, high-grade
      prostatic intraepithelial neoplasia, and hormone-dependent prostate cancer (HDPC)
      did not show any statistically significant difference. In contrast, statistically
      significant difference was reported in moderate/intense GOLPH3 expression in
      cases diagnosed with HDPC and castration resistant prostate cancer (CRPC) (P <
      0.0005). Moderate /intense expression of GOLPH3 was associated with androgen
      independence (P = 0.012), higher Gleason score (P = 0.017), bone metastasis (P =
      0.024), higher baseline prostate-specific antigen (PSA) (P = 0.038), and higher
      PSA nadir (P = 0.032). A significantly negative correlation was found between
      moderate/intense GOLPH3 expression and disease-free survival (DFS) (HR = 0.28, P
      = 0.012) and overall survival (OS) (HR = 0.42, P = 0.027). Univariated analysis
      indicated that moderate/intense GOLPH3 expression created a significantly
      prognostic impact in patients with CRPC. On the other hand, multivariate analysis
      indicated that GOLPH3 was a significantly independent prognostic factor of DFS (P
      = 0.027) in all prostate cancer patients. CONCLUSIONS: In this study, it was
      discovered that the overexpression of GOLPH3 is associated with the transition of
      prostate cancer from hormone sensitive phase to hormone refractory phase. GOLPH3
      might be an important prognostic factor of DFS and OS in patients with prostate
      cancer. In totality, GOLPH3 could be used as a novel candidate in devising a more
      effective therapeutic strategy to tackle CRPC. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1452541171722856.

PMID- 23006321
TI  - Comparison of the effects of esomeprazole and fundoplication on airway
      responsiveness in patients with gastro-oesophageal reflux disease.
AB  - INTRODUCTION: Gastro-oesophageal reflux disease (GORD) is suggested to cause or
      aggravate several respiratory conditions. Studies with proton pump inhibitors
      have resulted in only minor improvements in pulmonary outcomes in patients with
      GORD. It has been speculated that operative treatment of GORD might be more
      efficient as it also diminishes non-acidic reflux. OBJECTIVES: To compare the
      effects of esomeprazole 40 mg bid and fundoplication on airway responsiveness,
      forced expiratory volume in 1 s (FEV1), exhaled nitric oxide (NO) and respiratory
      symptoms in patients with moderate-to-severe GORD. METHODS: Sixty-nine GORD
      patients had methacholine inhalation challenge performed on them, and FEV1,
      exhaled NO and respiratory symptoms were measured at baseline, after a 3-month
      treatment with esomeprazole and 3 months after fundoplication. Primary outcome
      variable was dose-response slope (DRS), i.e. decline in FEV1 during methacholine
      challenge divided with the amount of methacholine administered (%/MUmol). Pre
      defined subgroup analysis was performed among those with concomitant asthma (n =
      12). RESULTS: There was no improvement in DRS, FEV1 or exhaled NO after
      esomeprazole treatment or fundoplication. Cough and dyspnoea measured with visual
      analog scale improved with esomeprazole treatment (P < 0.001), and further after
      fundoplication (P < 0.001). Among those with concomitant asthma, significant
      improvements in St George Respiratory Questionnaire (SGRQ) scores could be seen
      after fundoplication. CONCLUSIONS: Neither esomeprazole treatment nor
      fundoplication diminishes airway responsiveness or exhaled NO, or improves FEV1
      in patients with GORD. Improvements in respiratory symptoms and SGRQ scores after
      GORD treatments could be detected. However, as this was not a placebo-controlled
      study, the findings in these secondary endpoints should not be emphasised.
      ClinicalTrials.cov: NCT00994708.

PMID- 23006322
TI  - Defending the cornea with antibacterial fragments of keratin.
AB  - In addition to its role in refraction, the cornea forms a barrier between the eye
      and environmental and infectious insults. Corneal infections are surprisingly
      rare, suggesting that multiple aspects of the immune system are at play in
      mediating protection. In this issue of the JCI, Tam et al. describe the
      unexpected role of a structural protein, cytokeratin 6A, in this process.

PMID- 23006323
TI  - GATA believe it: new essential regulators of pancreas development.
AB  - Understanding the transcriptional mechanisms that underlie pancreas formation is
      central to the efforts to develop novel regenerative therapies for type 1
      diabetes. Recently, mutations in the transcription factor GATA6 were unexpectedly
      shown to be the most common cause of human pancreas agenesis. In this issue of
      the JCI, Carrasco et al. and Xuan et al. investigate the role of Gata6 and its
      paralogue Gata4 in mouse embryonic pancreas and show that GATA factors are
      essential regulators of the proliferation, morphogenesis, and differentiation of
      multipotent pancreatic progenitors.

PMID- 23006324
TI  - Looking in the miR-ror: TGF-beta-mediated activation of NF-kappaB in glioma.
AB  - The explosive growth in our understanding of the molecular underpinnings of
      glioblastomas has served as an instructive paradigm for other cancers. However,
      the exact nature by which many of the pathogenic drivers connect is less well
      known, and elucidation of relationships between critical genetic and signaling
      alterations may inform the development of therapeutic approaches to the disease.
      In this issue, Song et al. identify miR-182 induction as a mechanism by which TGF
      beta stimulation aberrantly activates NF-kappaB signaling in glioblastoma cells,
      clarifying a critical point of cross-talk between molecular signaling pathways.
      Their findings provide a greater understanding of the complex interplay between
      signaling pathways in cancer that may ultimately prove useful in the development
      of synergistic targeting approaches.

PMID- 23006325
TI  - Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis.
AB  - Pancreatic agenesis is a human disorder caused by defects in pancreas
      development. To date, only a few genes have been linked to pancreatic agenesis in
      humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas
      specific transcription factor 1a (PTF1A) reported in only 5 families with
      described cases. Recently, mutations in GATA6 have been identified in a large
      percentage of human cases, and a GATA4 mutant allele has been implicated in a
      single case. In the mouse, Gata4 and Gata6 are expressed in several endoderm
      derived tissues, including the pancreas. To analyze the functions of GATA4 and/or
      GATA6 during mouse pancreatic development, we generated pancreas-specific
      deletions of Gata4 and Gata6. Surprisingly, loss of either Gata4 or Gata6 in the
      pancreas resulted in only mild pancreatic defects, which resolved postnatally.
      However, simultaneous deletion of both Gata4 and Gata6 in the pancreas caused
      severe pancreatic agenesis due to disruption of pancreatic progenitor cell
      proliferation, defects in branching morphogenesis, and a subsequent failure to
      induce the differentiation of progenitor cells expressing carboxypeptidase A1
      (CPA1) and neurogenin 3 (NEUROG3). These studies address the conserved and
      nonconserved mechanisms underlying GATA4 and GATA6 function during pancreas
      development and provide a new mouse model to characterize the underlying
      developmental defects associated with pancreatic agenesis.

PMID- 23006326
TI  - Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin
      administration.
AB  - Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and
      is one of the leading causes of infertility in women aged 25-34.
      Hyperprolactinemia has been proposed to block ovulation through inhibition of
      GnRH release. Kisspeptin neurons, which express prolactin receptors, were
      recently identified as major regulators of GnRH neurons. To mimic the human
      pathology of anovulation, we continuously infused female mice with prolactin. Our
      studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced
      GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin
      administration restored gonadotropin secretion and ovarian cyclicity, suggesting
      that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our
      studies indicate that administration of kisspeptin may serve as an alternative
      therapeutic approach to restore the fertility of hyperprolactinemic women who are
      resistant or intolerant to dopamine agonists.

PMID- 23006327
TI  - Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell
      cytotoxicity.
AB  - The Fc receptor on NK cells, FcgammaRIIIA (CD16), has been extensively studied
      for its role in mediating antibody-dependent cellular cytotoxicity (ADCC). A
      homozygous missense mutation in CD16 (encoding a L66H substitution) is associated
      with severe herpesvirus infections in rare patients. Here, we identified a new
      patient with this CD16 mutation and compared the patient's NK cells to those of
      the originally reported patient. Patients with the L66H mutation had intact ADCC,
      but deficient spontaneous NK cell cytotoxicity and decreased surface expression
      of CD2, a coactivation receptor. Mechanistic studies in a human NK cell line, NK
      92, demonstrated that CD16 expression correlated with CD2 surface levels and
      enabled killing of a melanoma cell line typically resistant to CD16-deficient NK
      92 cells. An association between CD16 and CD2 was identified biochemically and at
      the immunological synapse, which elicited CD16 signaling after CD2 engagement.
      Stable expression of CD16 L66H in NK-92 cells recapitulated the patient
      phenotype, abrogating association of CD16 with CD2 as well as CD16 signaling
      after CD2 ligation. Thus, CD16 serves a role in NK cell-mediated spontaneous
      cytotoxicity through a specific association with CD2 and represents a potential
      mechanism underlying a human congenital immunodeficiency.

PMID- 23006328
TI  - Cytokeratins mediate epithelial innate defense through their antimicrobial
      properties.
AB  - Epithelial cells express antimicrobial proteins in response to invading
      pathogens, although little is known regarding epithelial defense mechanisms
      during healthy conditions. Here we report that epithelial cytokeratins have
      innate defense properties because they constitutively produce cytoprotective
      antimicrobial peptides. Glycine-rich C-terminal fragments derived from human
      cytokeratin 6A were identified in bactericidal lysate fractions of human corneal
      epithelial cells. Structural analysis revealed that these keratin-derived
      antimicrobial peptides (KDAMPs) exhibited coil structures with low alpha-helical
      content. Synthetic analogs of these KDAMPS showed rapid bactericidal activity
      against multiple pathogens and protected epithelial cells against bacterial
      virulence mechanisms, while a scrambled peptide showed no bactericidal activity.
      However, the bactericidal activity of a specific KDAMP was somewhat reduced by
      glycine-alanine substitutions. KDAMP activity involved bacterial binding and
      permeabilization, but the activity was unaffected by peptide charge or
      physiological salt concentration. Knockdown of cytokeratin 6A markedly reduced
      the bactericidal activity of epithelial cell lysates in vitro and increased the
      susceptibility of murine corneas to bacterial adherence in vivo. These data
      suggest that epithelial cytokeratins function as endogenous antimicrobial
      peptides in the host defense against infection and that keratin-derived
      antimicrobials may serve as effective therapeutic agents.

PMID- 23006329
TI  - TGF-beta induces miR-182 to sustain NF-kappaB activation in glioma subsets.
AB  - The strength and duration of NF-kappaB signaling are tightly controlled by
      multiple negative feedback mechanisms. However, in cancer cells, these feedback
      loops are overridden through unclear mechanisms to sustain oncogenic activation
      of NF-kappaB signaling. Previously, we demonstrated that overexpression of miR
      30e* directly represses IkappaBalpha expression and leads to hyperactivation of
      NF-kappaB. Here, we report that miR-182 was overexpressed in a different set of
      gliomas with relatively lower miR-30e* expression and that miR-182 directly
      suppressed cylindromatosis (CYLD), an NF-kappaB negative regulator. This
      suppression of CYLD promoted ubiquitin conjugation of NF-kappaB signaling pathway
      components and induction of an aggressive phenotype of glioma cells both in vitro
      and in vivo. Furthermore, we found that TGF-beta induced miR-182 expression,
      leading to prolonged NF-kappaB activation. Importantly, the results of these
      experiments were consistent with an identified significant correlation between
      miR-182 levels with TGF-beta hyperactivation and activated NF-kappaB in a cohort
      of human glioma specimens. These findings uncover a plausible mechanism for
      sustained NF-kappaB activation in malignant gliomas and may suggest a new target
      for clinical intervention in human cancer.

PMID- 23006331
TI  - Cognitive and affective dimensions of difficulties in emotional functioning in
      somatoform disorders and borderline personality disorder.
AB  - BACKGROUND: To study difficulties in emotional functioning in two mental
      disorders that have been associated with difficulties in identifying and
      modulating emotions: borderline personality disorder (BPD) and somatoform
      disorder (SoD). SAMPLING AND METHODS: In 472 psychiatric inpatients, difficulties
      in emotional functioning were measured using the Bermond-Vorst Alexithymia
      Questionnaire. RESULTS: Profiles of difficulties in emotional functioning were
      identified, suggesting that patients diagnosed with BPD with or without SoD were
      more likely to report difficulty identifying emotions and less likely to report
      reduced ability to fantasize or 'pensee operatoire' (externally oriented
      thinking) than patients diagnosed with SoD only and patients with mixed anxiety
      and affective disorders. SoD patients were more likely to report reduced ability
      to phantasize or pensee operatoire than difficulty identifying emotions. Patients
      with mixed anxiety and affective disorders were more likely to report reduced
      ability to experience emotions than patients diagnosed with BPD and/or SoD.
      CONCLUSIONS: By using a finer-grained perspective on difficulties in emotional
      functioning some evidence was found for the existence of cognitive-emotional
      profiles that may provide more clinically relevant information than alexithymia
      as just a unitary construct. Further research on cognitive-emotional profiles of
      difficulties in emotional functioning is needed to advance the understanding,
      diagnosis and treatment of mental disorders.

PMID- 23006330
TI  - GATA4 and GATA6 control mouse pancreas organogenesis.
AB  - Recently, heterozygous mutations in GATA6 have been found in neonatal diabetic
      patients with failed pancreatic organogenesis. To investigate the roles of GATA4
      and GATA6 in mouse pancreas organogenesis, we conditionally inactivated these
      genes within the pancreas. Single inactivation of either gene did not have a
      major impact on pancreas formation, indicating functional redundancy. However,
      double Gata4/Gata6 mutant mice failed to develop pancreata, died shortly after
      birth, and displayed hyperglycemia. Morphological defects in Gata4/Gata6 mutant
      pancreata were apparent during embryonic development, and the epithelium failed
      to expand as a result of defects in cell proliferation and differentiation. The
      number of multipotent pancreatic progenitors, including PDX1+ cells, was reduced
      in the Gata4/Gata6 mutant pancreatic epithelium. Remarkably, deletion of only 1
      Gata6 allele on a Gata4 conditional knockout background severely reduced
      pancreatic mass. In contrast, a single WT allele of Gata4 in Gata6 conditional
      knockout mice was sufficient for normal pancreatic development, indicating
      differential contributions of GATA factors to pancreas formation. Our results
      place GATA factors at the top of the transcriptional network hierarchy
      controlling pancreas organogenesis.

PMID- 23006333
TI  - Persistent pediatric contact leukoderma after exposure to butterfly
      electrocardiogram back pad: a report of three cases.
AB  - Contact leukoderma or chemical leukoderma refers to hypopigmentation related to
      the application of chemical compounds to the skin. Hypopigmentation can occur
      with or without preceding inflammatory eczematous changes. We present three cases
      of contact leukoderma associated with exposure to a new type of electrocardiogram
      electrode back pad. 

PMID- 23006332
TI  - 4-Chloropropofol enhances chloride currents in human hyperekplexic and artificial
      mutated glycine receptors.
AB  - BACKGROUND: The mammalian neurological disorder hereditary hyperekplexia can be
      attributed to various mutations of strychnine sensitive glycine receptors. The
      clinical symptoms of "startle disease" predominantly occur in the newborn leading
      to convulsive hypertonia and an exaggerated startle response to unexpected mild
      stimuli. Amongst others, point mutations R271Q and R271L in the alpha1-subunit of
      strychnine sensitive glycine receptors show reduced glycine sensitivity and cause
      the clinical symptoms of hyperekplexia.Halogenation has been shown to be a
      crucial structural determinant for the potency of a phenolic compound to
      positively modulate glycine receptor function.The aim of this in vitro study was
      to characterize the effects of 4-chloropropofol (4-chloro-2,6-dimethylphenol) at
      four glycine receptor mutations. METHODS: Glycine receptor subunits were
      expressed in HEK 293 cells and experiments were performed using the whole-cell
      patch-clamp technique. RESULTS: 4-chloropropofol exerted a positive allosteric
      modulatory effect in a low sub-nanomolar concentration range at the wild type
      receptor (EC50 value of 0.08 +/- 0.02 nM) and in a micromolar concentration range
      at the mutations (1.3 +/- 0.6 MUM, 0.1 +/- 0.2 MUM, 6.0 +/- 2.3 MUM and 55 +/- 28
      MUM for R271Q, L, K and S267I, respectively). CONCLUSIONS: 4-chloropropofol might
      be an effective compound for the activation of mutated glycine receptors in
      experimental models of startle disease.

PMID- 23006334
TI  - Non-specific effects of diphtheria-tetanus-pertussis and measles vaccinations? An
      analysis of surveillance data from Navrongo, Ghana.
AB  - OBJECTIVES: Studies from low-income countries have suggested that routine
      vaccinations may have non-specific effects on child mortality; measles vaccine
      (MV) is associated with lower mortality and diphtheria-tetanus-pertussis (DTP)
      with relatively higher mortality. We used data from Navrongo, Ghana, to examine
      the impact of vaccinations on child mortality. METHODS: Vaccination status was
      assessed at the initiation of a trial of vitamin A supplementation and after 12
      and 24 months of follow-up. Within the placebo group, we compared the mortality
      over the first 4 months and the full 2 years of follow-up for different
      vaccination status groups with different likelihoods of additional vaccinations
      during follow-up. The frequency of additional vaccinations was assessed among
      children whose vaccination card was seen at 12 and 24 months of follow-up.
      RESULTS: Among children with a vaccination card, more than 75% received missing
      DTP or MV during the first 12 months of follow-up, whereas only 25% received
      these vaccines among children with no vaccination card at enrollment. Children
      without a card at enrollment had a significant threefold higher mortality over
      the 2-year follow-up period than those fully vaccinated. The small group of
      children with DTP3-4 but no MV at enrollment had lower mortality than children
      without a card and had the same mortality as fully vaccinated children. In
      contrast, children with 1-2 DTP doses but no MV had a higher mortality during the
      first 4 months than children without a card [MRR = 1.65 (0.95, 2.87)]; compared
      with the fully vaccinated children, they had significantly higher mortality after
      4 months [MRR = 2.38 (1.07, 5.30)] and after 2 years [MRR = 2.41 (1.41, 4.15)].
      Children with 0-2 DTP doses at enrollment had higher mortality after 4 months
      (MRR = 1.67 (0.82, 3.43) and after 2 years [MRR = 1.85 (1.16, 2.95)] than
      children who had all three doses of DTP at enrollment. CONCLUSIONS: As
      hypothesised, DTP vaccination was associated with higher child mortality than
      measles vaccination. To optimise vaccination policies, routine vaccinations need
      to be evaluated in randomised trials measuring the impact on survival.

PMID- 23006335
TI  - Sensorimotor adaptation training's effect on head stabilization in response to a
      lateral perturbation in older adults.
AB  - The goal of this study was to determine if exposure to sensorimotor adaptation
      training improved head stabilization in older adults. Sixteen participants, age
      66-81 yr, were assigned at random to the control group (n = 8) or the
      experimental group (n = 8). Both groups first completed 6 trials of walking a
      foam pathway consisting of a moveable platform that induced a lateral
      perturbation during walking. Head-in-space and trunk-in-space angular velocities
      were collected. Participants from both groups then trained twice per week for 4
      wk. Both groups walked on a treadmill for 20 min. The control group viewed a
      static scene. The experimental group viewed a rotating visual scene that provided
      a perceptual-motor mismatch. After training, both groups were retested on the
      perturbation pathway test. The experimental group used a movement strategy that
      preserved head stabilization compared with the controls (p < .05). This training
      effect was not retained after 4 wk. 

PMID- 23006336
TI  - Understanding the factors that influence the adoption and meaningful use of
      social media by physicians to share medical information.
AB  - BACKGROUND: Within the medical community there is persistent debate as to whether
      the information available through social media is trustworthy and valid, and
      whether physicians are ready to adopt these technologies and ultimately embrace
      them as a format for professional development and lifelong learning. OBJECTIVE:
      To identify how physicians are using social media to share and exchange medical
      information with other physicians, and to identify the factors that influence
      physicians' use of social media as a component of their lifelong learning and
      continuing professional development. METHODS: We developed a survey instrument
      based on the Technology Acceptance Model, hypothesizing that technology usage is
      best predicted by a physician's attitudes toward the technology, perceptions
      about the technology's usefulness and ease of use, and individual factors such as
      personal innovativeness. The survey was distributed via email to a random sample
      of 1695 practicing oncologists and primary care physicians in the United States
      in March 2011. Responses from 485 physicians were analyzed (response rate
      28.61%). RESULTS: Overall, 117 of 485 (24.1%) of respondents used social media
      daily or many times daily to scan or explore medical information, whereas 69 of
      485 (14.2%) contributed new information via social media on a daily basis. On a
      weekly basis or more, 296 of 485 (61.0%) scanned and 223 of 485 (46.0%)
      contributed. In terms of attitudes toward the use of social media, 279 of 485
      respondents (57.5%) perceived social media to be beneficial, engaging, and a good
      way to get current, high-quality information. In terms of usefulness, 281 of 485
      (57.9%) of respondents stated that social media enabled them to care for patients
      more effectively, and 291 of 485 (60.0%) stated it improved the quality of
      patient care they delivered. The main factors influencing a physician's usage of
      social media to share medical knowledge with other physicians were perceived ease
      of use and usefulness. Respondents who had positive attitudes toward the use of
      social media were more likely to use social media and to share medical
      information with other physicians through social media. Neither age nor gender
      had a significant impact on adoption or usage of social media. CONCLUSIONS: Based
      on the results of this study, the use of social media applications may be seen as
      an efficient and effective method for physicians to keep up-to-date and to share
      newly acquired medical knowledge with other physicians within the medical
      community and to improve the quality of patient care. Future studies are needed
      to examine the impact of the meaningful use of social media on physicians'
      knowledge, attitudes, skills, and behaviors in practice.

PMID- 23006337
TI  - Twisted structure of a cyclic hexapeptide containing a combination of alternating
      L-Leu-D-Leu-Aib segments.
AB  - We designed and synthesized a C(2)-symmetric cyclic hexapeptide, cyclo(L-Leu-D
      Leu-Aib)(2) (2), which contains L- and D-amino acids and achiral Aib residues.
      The conformation of 2 was analyzed in the crystalline state and in solution,
      which was a unique figure-eight-shaped conformation.

PMID- 23006338
TI  - Phosphate as a sensor and signaling molecule.
AB  - In prokaryotes and eukaryotes inorganic phosphate plays a vital role in many
      cellular and biological processes. Maintenance of proper phosphate homeostasis is
      therefore essential and any deviation from that state can lead to several acute
      and chronic disease states. In order to maintain physiological levels, a tightly
      regulated phosphate sensing and signaling mechanism needs to exist. The earliest
      and best characterized mechanisms of phosphate sensing and signaling have been
      described in yeast and bacteria involving the Pho regulon. The Pho regulon has
      been shown to function in a coordinated fashion in order to meet the cellular
      needs of the organism. Studies have also shown that the protein kinase A (PKA)
      signaling pathway is involved in phosphate metabolism. In eukaryotes, due to the
      complexity of the regulatory mechanisms and involvement of several key regulators
      of phosphate secreted from different organs, it has been difficult to identify
      the phosphate sensor. Nonetheless the crosstalk between organs in response to
      phosphate provides strong evidence to support the existence of such a mechanism.
      This review will focus on this evidence and highlight the parallels tha exist
      with the Pho regulon. We will focus on the kidney-arathyroid, kidney-intestinal,
      parathyroid-intestinal, kidney-bone, and finally the parathyroid-bone axes.

PMID- 23006339
TI  - Minimal change disease in graft versus host disease: a podocyte response to the
      graft?
AB  - Nephrotic syndrome is a rare complication of hematopoietic cell transplantation.
      It has been suggested that nephrotic syndrome may represent a limited form of
      graft-versus-host disease although the pathological link between these two
      entities remains unclear. In this paper, we report a case of a 61-year-old female
      who underwent nonmyeloablative allogenic stem cell transplantation for T-cell
      prolymphocytic leukemia and subsequently developed biopsy proven minimal change
      disease shortly after cessation of her immunosuppression therapy. Urinary CD80
      was markedly elevated during active disease and disappeared following
      corticosteroid-induced remission. We hypothesize that alloreactive donor T cells
      target the kidney and induce podocyte expression of CD80 that results in
      proteinuria from limited 'graft versus host' disease. 

PMID- 23006340
TI  - Association of IgG co-deposition with serum levels of galactose-deficient IgA1 in
      pediatric IgA nephropathy.
AB  - OBJECTIVE: To determine whether the absence of mesangial IgG deposits is
      associated with the absence of elevated blood levels of galactose-deficient IgA1
      (Gd-IgA1) in pediatric patients with IgA nephropathy (IgAN). DESIGN AND METHODS:
      Serum Gd-IgA1 levels were determined by ELISA using an N-acetylgalactosamine
      specific lectin from Helix aspersa. Levels of Gd-IgA1 above the 90th percentile
      for healthy pediatric controls were considered to be elevated. Renal biopsy
      samples were examined by immunofluorescence for presence and intensity of
      staining for IgA, IgG, IgM, C3 and C1q and by light microscopy for histological
      changes. Findings were graded by a single pathologist (L. Gaber) at UTHSC until
      2007 and by NephropathTM (Little Rock, AR, USA) thereafter. Staining for the
      mesangial deposits was considered negative when intensity was trace or less, and
      positive at greater intensity. Fisher's exact test was used to determine
      significance of 2 * 2 tables. RESULTS: Serum samples were obtained from 30
      patients with IgAN diagnosed before age 18 years. Male:female ratio was 2.3:1.
      Twenty were Caucasian and 10 were African-American. Blood was obtained within 3
      months of biopsy (incident cases) for 12, while 18 provided blood > 3 months
      after biopsy (prevalent cases). Serum Gd-IgA1 level was elevated in 23 (77%) of
      cases and 20 (67%) had a biopsy positive for IgG. Of those 20 patients, 18 (90%)
      had an elevated serum Gd-IgA1 level, whereas 5 (50%) of patients with biopsies
      without IgG had a normal serum Gd-IgA1 level (p = 0.026). SUMMARY: In this small
      study we found a weak association between the absence of IgG in the biopsy and
      normal serum Gd-IgA1 level.

PMID- 23006341
TI  - Molecular mediators of favism-induced acute kidney injury.
AB  - Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase
      deficiency (favism) may lead to severe hemolytic crises and decreased renal
      function. Renal biopsy findings exploring the molecular mechanisms of renal
      damage in favism have not been previously reported. We report a case of favism
      associated acute kidney injury in which renal biopsy showed acute tubular
      necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit
      areas were characterized by the presence of oxidative stress markers (NADPH-p22
      phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger
      receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and
      CD163 positive cells were observed in some glomeruli. These results identify both
      glomerular and tubular involvement in favism-associated acute kidney injury and
      suggest novel therapeutic targets to prevent or accelerate recovery from acute
      kidney injury. 

PMID- 23006342
TI  - Ureteroscopic treatment of patients with small, painful, non-obstructing renal
      stones: the small stone syndrome.
AB  - AIMS: Although it is thought that renal colic results from urinary tract
      obstruction, some patients evaluated for renal colic are found to have no source
      for their pain other than small, non-obstructing renal calyceal stones. We refer
      to this as "the small stone syndrome". We aim to determine if small non
      obstructing calyceal stones may also cause pain and that treatment may relieve
      this pain. METHOD: A retrospective chart review was performed to identify
      patients with non-obstructing calyceal stones (<= 4 mm in diameter) evaluated for
      flank pain and treated by ureteroscopy. Patients completed a follow-up
      questionnaire regarding pre- and postoperative pain and quality of life (QOL).
      RESULTS: 13 patients were included in the analysis. Mean stone diameter was 3 mm
      (range 1.5 - 4.0 mm). Following ureteroscopy, 11 (85%) patients reported complete
      resolution of pain and 2 (15%) reported partial resolution. 12 patients were able
      to describe preoperative and postoperative QOL and of these, 8 (67%) had improved
      QOL, 4 (33%) had no change, and none reported worsening. Follow-up imaging was
      available in 10 patients: stone free in 6 (60%), reduction in stone size in 3
      (30%), and stone unchanged in 1 (10%). CONCLUSIONS: Ureteroscopic treatment of
      painful small, non-obstructing renal calyceal stones achieved complete or partial
      resolution of pain in all patients and improvement in QOL in a majority of
      patients.

PMID- 23006343
TI  - Preoperative multidetector-row computed tomography scan staging for lymphatic
      gastric cancer spread.
AB  - BACKGROUND: Multidetector-row computed tomography (MDCT) is commonly used to
      stage patients with gastric cancer, even though the technique often shows low
      specificity for lymph-node involvement. METHODS: In this study, 111 patients with
      gastric cancer who consecutively underwent MDCT scan followed by radical surgical
      treatment at our hospital were retrospectively evaluated. RESULTS: In total, 3632
      lymph nodes from 643 lymphatic stations were studied and then correlated with
      radiological features. Lymph-node size was not always associated with
      infiltration. Of the 261 lymph-node stations that were not radiologically
      detected, 60 (22.9%) were infiltrated. There were 108 stations with lymph nodes
      larger than 10 mm seen on MDCT, of which 67 (62%) had lymphatic invasion. The
      sensitivity was 32.6%, specificity 90.6%, positive predictive value 62.0%,
      negative predictive value 74.2%, and accuracy 72.1%. When three lymph nodes, at
      least one of which was larger than 10 mm, were detected in the same station,
      infiltration was confirmed with 99% specificity in 93.8% of patients. Moreover,
      all of the 13 patients in whom three lymph nodes larger than 10 mm were detected
      in different neighboring stations had lymphatic invasion. CONCLUSIONS: Although
      presence of lymph nodes greater than 10 mm in size is not, in itself, sufficient
      to confirm lymphatic invasion, nodal involvement can be hypothesized when
      associated images are detected by MDCT.

PMID- 23006344
TI  - Autologous adipose tissue-derived stem cells for the treatment of Crohn's
      fistula: a phase I clinical study.
AB  - The present study was designed to evaluate the safety and potential of adipose
      tissue-derived stem cells (ASCs) for the treatment of Crohn's fistula. In this
      dose escalation study, patients were sequentially enrolled into three dosing
      groups with at least three patients per group.  The first three patients (group
      1) were given 1 * 10(7) cells/ml. After 4 weeks, this dose was deemed safe, and
      so an additional four patients (group 2) were given 2 * 10(7) cells/ml. Four
      weeks later, after which this second dose was deemed safe, a third and  final
      group of three patients were given 4 * 10(7) cells/ml. Each patient was followed
      for a minimum of 8 weeks. Patients who showed complete healing at week 8 were
      followed up for an additional 6 months. Efficacy endpoint was complete healing at
      week 8 after injection, defined  as complete closure of the fistula track and
      internal and external openings without drainage or signs of inflammation. There
      were no grade 3 or 4 severity adverse events, and there were no adverse events
      related to the study drug. Two patients in group 2, treated with 2 * 10(7) 
      ASCs/ml, showed complete healing at week 8 after injection. Of the three patients
      enrolled in group 3, treated with 4 * 10(7) ASCs/ml, one showed complete healing.
      Outcome in another patient was assessed as partial healing due to incomplete
      closure of the external opening, although  the inside of fistula track was filled
      considerably and there was no drainage. All three patients with complete healing
      at week 8 showed a sustained effect without recurrence 8 months after injection.
      In conclusion, this study demonstrates the tolerability, safety, and potential
      efficacy of  ASCs for the treatment of Crohn's fistula and provides support for
      further clinical study.

PMID- 23006345
TI  - Operational framework for nonlocality.
AB  - Because of the importance of entanglement for quantum information purposes, a
      framework has been developed for its characterization and quantification as a
      resource based on the following operational principle: entanglement among N
      parties cannot be created by local operations and classical communication, even
      when N-1 parties collaborate. More recently, nonlocality has been identified as
      another resource, alternative to entanglement and necessary for device
      independent quantum information protocols. We introduce an operational framework
      for nonlocality based on a similar principle: nonlocality among N parties cannot
      be created by local operations and allowed classical communication even when N-1
      parties collaborate. We then show that the standard definition of multipartite
      nonlocality, due to Svetlichny, is inconsistent with this operational approach:
      according to it, genuine tripartite nonlocality could be created by two
      collaborating parties. We finally discuss alternative definitions for which
      consistency is recovered.

PMID- 23006346
TI  - Phase-space approach to solving the time-independent Schrodinger equation.
AB  - We propose a method for solving the time-independent Schrodinger equation based
      on the von Neumann (vN) lattice of phase space Gaussians. By incorporating
      periodic boundary conditions into the vN lattice [F. Dimler et al., New J. Phys.
      11, 105052 (2009)], we solve a longstanding problem of convergence of the vN
      method. This opens the door to tailoring quantum calculations to the underlying
      classical phase space structure while retaining the accuracy of the Fourier grid
      basis. The method has the potential to provide enormous numerical savings as the
      dimensionality increases. In the classical limit, the method reaches the
      remarkable efficiency of one basis function per one eigenstate. We illustrate the
      method for a challenging two-dimensional potential where the Fourier grid method
      breaks down.

PMID- 23006347
TI  - Quantum discord bounds the amount of distributed entanglement.
AB  - The ability to distribute quantum entanglement is a prerequisite for many
      fundamental tests of quantum theory and numerous quantum information protocols.
      Two distant parties can increase the amount of entanglement between them by means
      of quantum communication encoded in a carrier that is sent from one party to the
      other. Intriguingly, entanglement can be increased even when the exchanged
      carrier is not entangled with the parties. However, in light of the defining
      property of entanglement stating that it cannot increase under classical
      communication, the carrier must be quantum. Here we show that, in general, the
      increase of relative entropy of entanglement between two remote parties is
      bounded by the amount of nonclassical correlations of the carrier with the
      parties as quantified by the relative entropy of discord. We study implications
      of this bound, provide new examples of entanglement distribution via unentangled
      states, and put further limits on this phenomenon.

PMID- 23006348
TI  - Coherence-protected quantum gate by continuous dynamical decoupling in diamond.
AB  - In order to achieve reliable quantum-information processing results, we need to
      protect quantum gates along with the qubits from decoherence. Here we demonstrate
      experimentally on a nitrogen-vacancy system that by using a continuous-wave
      dynamical decoupling method, we might not only prolong the coherence time by
      about 20 times but also protect the quantum gates for the duration of the
      controlling time. This protocol shares the merits of retaining the superiority of
      prolonging the coherence time and at the same time easily combining with quantum
      logic tasks. This method can be useful in tasks where the duration of quantum
      controlling exceeds far beyond the dephasing time.

PMID- 23006349
TI  - Longer-baseline telescopes using quantum repeaters.
AB  - We present an approach to building interferometric telescopes using ideas of
      quantum information. Current optical interferometers have limited baseline
      lengths, and thus limited resolution, because of noise and loss of signal due to
      the transmission of photons between the telescopes. The technology of quantum
      repeaters has the potential to eliminate this limit, allowing in principle
      interferometers with arbitrarily long baselines.

PMID- 23006350
TI  - Practical experimental certification of computational quantum gates using a
      twirling procedure.
AB  - Because of the technical difficulty of building large quantum computers, it is
      important to be able to estimate how faithful a given implementation is to an
      ideal quantum computer. The common approach of completely characterizing the
      computation process via quantum process tomography requires an exponential amount
      of resources, and thus is not practical even for relatively small devices. We
      solve this problem by demonstrating that twirling experiments previously used to
      characterize the average fidelity of quantum memories efficiently can be easily
      adapted to estimate the average fidelity of the experimental implementation of
      important quantum computation processes, such as unitaries in the Clifford group,
      in a practical and efficient manner with applicability in current quantum
      devices. Using this procedure, we demonstrate state-of-the-art coherent control
      of an ensemble of magnetic moments of nuclear spins in a single crystal solid by
      implementing the encoding operation for a 3-qubit code with only a 1% degradation
      in average fidelity discounting preparation and measurement errors. We also
      highlight one of the advances that was instrumental in achieving such high
      fidelity control.

PMID- 23006351
TI  - Antipersistent random walk in a two state flashing magnetic potential.
AB  - We reveal the subdiffusive dynamics of paramagnetic colloids subjected to a two
      state flashing potential generated by periodic modulation of a magnetic bubble
      lattice. The particles perform a random walklike motion with antipersistent
      nature, showing for certain field parameters a crossover from subdiffusive to an
      enhanced diffusive behavior. We elucidate the stationary nature (no aging) of the
      subdiffusive process and stress its similarity with the random walk on a random
      walk model.

PMID- 23006352
TI  - Measurement of the velocity of neutrinos from the CNGS beam with the large volume
      detector.
AB  - We report the measurement of the time of flight of ~17 GeV nu(MU) on the CNGS
      baseline (732 km) with the Large Volume Detector (LVD) at the Gran Sasso
      Laboratory. The CERN-SPS accelerator has been operated from May 10th to May 24th
      2012, with a tightly bunched-beam structure to allow the velocity of neutrinos to
      be accurately measured on an event-by-event basis. LVD has detected 48 neutrino
      events, associated with the beam, with a high absolute time accuracy. These
      events allow us to establish the following limit on the difference between the
      neutrino speed and the light velocity: -3.8 * 10(-6) < (v(nu)-c)/c < 3.1 * 10(-6)
      (at 99% C.L.). This value is an order of magnitude lower than previous direct
      measurements.

PMID- 23006353
TI  - Optical transitions in highly charged californium ions with high sensitivity to
      variation of the fine-structure constant.
AB  - We study electronic transitions in highly charged Cf ions that are within the
      frequency range of optical lasers and have very high sensitivity to potential
      variations in the fine-structure constant, alpha. The transitions are in the
      optical range despite the large ionization energies because they lie on the level
      crossing of the 5f and 6p valence orbitals in the thallium isoelectronic
      sequence. Cf(16+) is a particularly rich ion, having several narrow lines with
      properties that minimize certain systematic effects. Cf(16+) has very large
      nuclear charge and large ionization energy, resulting in the largest alpha
      sensitivity seen in atomic systems. The lines include positive and negative
      shifters.

PMID- 23006354
TI  - Local magnetic turbulence and TeV-PeV cosmic ray anisotropies.
AB  - In the energy range from ~10(12)  eV to ~10(15)  eV, the Galactic cosmic ray flux
      has anisotropies both on large scales, with an amplitude of the order of 0.1%,
      and on scales between ?10 degrees  and ?30 degrees , with amplitudes smaller by a
      factor of a few. With a diffusion coefficient inferred from Galactic cosmic ray
      chemical abundances, the diffusion approximation predicts a dipolar anisotropy of
      comparable size, but does not explain the smaller scale anisotropies. We
      demonstrate here that energy dependent smaller scale anisotropies naturally arise
      from the local concrete realization of the turbulent magnetic field within the
      cosmic ray scattering length. We show how such anisotropies could be calculated
      if the magnetic field structure within a few tens of parsecs from Earth were
      known.

PMID- 23006355
TI  - Transient resonances in the inspirals of point particles into black holes.
AB  - We show that transient resonances occur in the two-body problem in general
      relativity for spinning black holes in close proximity to one another when one
      black hole is much more massive than the other. These resonances occur when the
      ratio of polar and radial orbital frequencies, which is slowly evolving under the
      influence of gravitational radiation reaction, passes through a low order
      rational number. At such points, the adiabatic approximation to the orbital
      evolution breaks down, and there is a brief but order unity correction to the
      inspiral rate. The resonances cause a perturbation to orbital phase of order a
      few tens of cycles for mass ratios ~10(-6), make orbits more sensitive to changes
      in initial data (though not quite chaotic), and are genuine nonperturbative
      effects that are not seen at any order in a standard post-Newtonian expansion.
      Our results apply to an important potential source of gravitational waves, the
      gradual inspiral of white dwarfs, neutron stars, or black holes into much more
      massive black holes. Resonances' effects will increase the computational
      challenge of accurately modeling these sources.

PMID- 23006357
TI  - Refining new-physics searches in B->Dtaunu with lattice QCD.
AB  - The semileptonic decay channel B->Dtaunu is sensitive to the presence of a scalar
      current, such as that mediated by a charged-Higgs boson. Recently, the BABAR
      experiment reported the first observation of the exclusive semileptonic decay B
      >Dtau(-)nu, finding an approximately 2sigma disagreement with the standard-model
      prediction for the ratio R(D)=BR(B->Dtaunu)/BR(B->Dlnu), where l = e,MU. We
      compute this ratio of branching fractions using hadronic form factors computed in
      unquenched lattice QCD and obtain R(D)=0.316(12)(7), where the errors are
      statistical and total systematic, respectively. This result is the first standard
      model calculation of R(D) from ab initio full QCD. Its error is smaller than that
      of previous estimates, primarily due to the reduced uncertainty in the scalar
      form factor f(0)(q(2)). Our determination of R(D) is approximately 1sigma higher
      than previous estimates and, thus, reduces the tension with experiment. We also
      compute R(D) in models with electrically charged scalar exchange, such as the
      type-II two-Higgs-doublet model. Once again, our result is consistent with, but
      approximately 1sigma higher than, previous estimates for phenomenologically
      relevant values of the scalar coupling in the type-II model. As a by-product of
      our calculation, we also present the standard-model prediction for the
      longitudinal-polarization ratio P(L)(D)=0.325(4)(3).

PMID- 23006360
TI  - theta dependence of the deconfinement temperature in Yang-Mills theories.
AB  - We determine the theta dependence of the deconfinement temperature of SU(3) pure
      gauge theory, finding that it decreases in the presence of a topological theta
      term. We do that by performing lattice simulations at imaginary theta, then
      exploiting analytic continuation. We also give an estimate of such dependence in
      the limit of a large number of colors N and compare it with our numerical
      results.

PMID- 23006361
TI  - Full QED+QCD low-energy constants through reweighting.
AB  - The effect of sea quark electromagnetic charge on meson masses is investigated,
      and first results for full QED+QCD low-energy constants are presented. The
      electromagnetic charge for sea quarks is incorporated in quenched QED+full QCD
      lattice simulations by a reweighting method. The reweighting factor, which
      connects quenched and unquenched QED, is estimated using a stochastic method on
      2+1 flavor dynamical domain-wall quark ensembles.

PMID- 23006363
TI  - Pseudospin symmetry in single particle resonant states.
AB  - The pseudospin symmetry (PSS) is a relativistic dynamical symmetry connected with
      the small component of the Dirac spinor. The origin of PSS in single particle
      bound states in atomic nuclei has been revealed and studied extensively. By
      examining the zeros of Jost functions corresponding to the small components of
      Dirac wave functions and phase shifts of continuum states, we show that the PSS
      in single particle resonant states in nuclei is conserved when the attractive
      scalar and repulsive vector potentials have the same magnitude but opposite sign.
      The exact conservation and the breaking of the PSS are illustrated for single
      particle resonances in spherical square-well and Woods-Saxon potentials.

PMID- 23006364
TI  - NMR chemical shift in an electronic state with arbitrary degeneracy.
AB  - We present a theory of nuclear magnetic resonance shielding tensors for
      electronic states with arbitrary degeneracy. The shieldings are here expressed in
      terms of generalized Zeeman (g((k))) and hyperfine (A((k))) tensors, of all ranks
      k allowed by the size of degeneracy. Contrary to recent proposals [T. O. Pennanen
      and J. Vaara, Phys. Rev. Lett. 100, 133002 (2008)], our theory is valid in the
      strong spin-orbit coupling limit. Ab initio calculations for the fourfold
      degenerate Gamma(8) ground state of lanthanide-doped fluorite crystals CaF(2):Ln
      (Ln=Pr(2+), Nd(3+), Sm(3+), and Dy(3+)) show that previously neglected
      contributions can account for more than 50% of the paramagnetic shift.

PMID- 23006365
TI  - Strong coupling between molecular excited states and surface plasmon modes of a
      slit array in a thin metal film.
AB  - We demonstrate strong coupling between molecular excited states and surface
      plasmon modes of a slit array in a thin metal film. The coupling manifests itself
      as an anticrossing behavior of the two newly formed polaritons. As the coupling
      strength grows, a new mode emerges, which is attributed to long-range molecular
      interactions mediated by the plasmonic field. The new, molecular-like mode repels
      the polariton states, and leads to an opening of energy gaps both below and above
      the asymptotic free molecule energy.

PMID- 23006366
TI  - N-body Efimov states from two-particle noise.
AB  - The ground state energies of universal N-body clusters tied to Efimov trimers,
      for N even, are shown to be encapsulated in the statistical distribution of two
      particles interacting with a background auxiliary field at large Euclidean time
      when the interaction is tuned to the unitary point. Numerical evidence that this
      distribution is log normal is presented, allowing one to predict the ground state
      energies of the N-body system.

PMID- 23006367
TI  - Direct visualization of laser-driven electron multiple scattering and tunneling
      distance in strong-field ionization.
AB  - Using a simple model of strong-field ionization of atoms that generalizes the
      well-known 3-step model from 1D to 3D, we show that the experimental
      photoelectron angular distributions resulting from laser ionization of xenon and
      argon display prominent structures that correspond to electrons that pass by
      their parent ion more than once before strongly scattering. The shape of these
      structures can be associated with the specific number of times the electron is
      driven past its parent ion in the laser field before scattering. Furthermore, a
      careful analysis of the cutoff energy of the structures allows us to
      experimentally measure the distance between the electron and ion at the moment of
      tunnel ionization. This work provides new physical insight into how atoms ionize
      in strong laser fields and has implications for further efforts to extract atomic
      and molecular dynamics from strong-field physics.

PMID- 23006368
TI  - Inelastic confinement-induced resonances in low-dimensional quantum systems.
AB  - A theoretical model is presented describing the confinement-induced resonances
      observed in the recent loss experiment of Haller et al. [Phys. Rev. Lett. 104,
      153203 (2010)]. These resonances originate from possible molecule formation due
      to the coupling of center-of-mass and relative motion. A corresponding model is
      verified by ab initio calculations and predicts the resonance positions in 1D as
      well as in 2D confinement in agreement with the experiment. This resolves the
      contradiction of the experimental observations to previous theoretical
      predictions.

PMID- 23006369
TI  - Positronium hyperfine interval measured via saturated absorption spectroscopy.
AB  - We report Doppler-free measurements of the positronium (Ps) Lyman-alpha
      transition using saturated absorption spectroscopy. In addition to a Lamb dip at
      wavelength lambda(L) = 243.0218 +/- 0.0005 nm, we also observed a crossover
      resonance at lambda(C) = 243.0035 +/- 0.0005 nm, arising from the excitation of
      1(3)S(1) atoms to Zeeman mixed 2P states, followed by stimulated emission to the
      1(1)S(0) ground state. Since (lambda(L)-lambda(C)) is related to the Ps hyperfine
      interval E(hfs), this observation constitutes the first optical measurement of
      this quantity and yields E(hfs) = 198.4 +/- 4.2 GHz. We describe improvements to
      the methodology that could lead to the ~ppm level of precision required to
      address the long-standing discrepancy between QED calculations and precision
      experiments using microwave radiation to induce transitions between Zeeman
      shifted triplet Ps states.

PMID- 23006370
TI  - Subcycle ac stark shift of helium excited states probed with isolated attosecond
      pulses.
AB  - Recent advances in attosecond science have relied upon the nearly instantaneous
      response of free electrons to an external field. However, it is still not clear
      whether bound electrons are able to rearrange on sublaser cycle time scales.
      Here, we probe the optical Stark shifts induced by a few-cycle near infrared
      laser field in helium bound states using isolated attosecond pulses in a
      transient absorption scheme and uncover a subcycle laser-induced energy level
      shift of the laser-dressed 1s3p state.

PMID- 23006371
TI  - Strong coupling of surface plasmon polaritons in monolayer graphene sheet arrays.
AB  - Here we investigate theoretically and numerically the coupling between surface
      plasmon polaritons (SPPs) in monolayer graphene sheet arrays that have a period
      much smaller than the wavelength. We show that when the collective SPP is excited
      with an out-of-phase illumination, the beam tends to propagate toward the
      opposite direction of the Bloch momentum, reflecting a negative coupling between
      the constituent SPPs. In contrast, for in-phase illumination, the incident beam
      is split into two collective SPPs that are highly collimated and display low
      propagation loss. Moreover, the coupling between the individual SPPs results in a
      reduction of the modal wavelength of the SPP in comparison with that of a single
      graphene sheet.

PMID- 23006372
TI  - Geometry of the vapor layer under a leidenfrost drop.
AB  - In the Leidenfrost effect, liquid drops deposited on a hot surface levitate on a
      thin vapor cushion fed by evaporation of the liquid. This vapor layer forms a
      concave depression in the drop interface. Using laser-light interference coupled
      to high-speed imaging, we measured the radius, curvature, and height of the vapor
      pocket, as well as nonaxisymmetric fluctuations of the interface for water drops
      at different temperatures. The geometry of the vapor pocket depends primarily on
      the drop size and not on the substrate temperature.

PMID- 23006373
TI  - Revival of classical vortex generators now for transition delay.
AB  - Classical vortex generators, known for their efficiency in delaying or even
      inhibiting boundary layer separation, are here shown to be coveted devices for
      transition to turbulence delay. The present devices are miniature with respect to
      classical vortex generators but are tremendously powerful in modulating the
      laminar boundary layer in the direction orthogonal to the base flow and parallel
      to the surface. The modulation generates an additional term in the perturbation
      energy equation, which counteracts the wall-normal production term and, hence,
      stabilizes the flow. Our experimental results show that these devices are really
      effective in delaying transition, but we also reveal their Achilles' heel.

PMID- 23006374
TI  - Effect of weak rotation on large-scale circulation cessations in turbulent
      convection.
AB  - We investigate the effect of weak rotation on the large-scale circulation (LSC)
      of turbulent Rayleigh-Benard convection, using the theory for cessations in a low
      dimensional stochastic model of the flow previously studied. We determine the
      cessation frequency of the LSC as a function of rotation, and calculate the
      statistics of the amplitude and azimuthal velocity fluctuations of the LSC as a
      function of the rotation rate for different Rayleigh numbers. Furthermore, we
      show that the tails of the reorientation PDF remain unchanged for rotating
      systems, while the distribution of the LSC amplitude and correspondingly the
      cessation frequency are strongly affected by rotation. Our results are in close
      agreement with experimental observations.

PMID- 23006375
TI  - Generating periodic terahertz structures in a relativistic electron beam through
      frequency down-conversion of optical lasers.
AB  - We report generation of density modulation at terahertz (THz) frequencies in a
      relativistic electron beam through laser modulation of the beam longitudinal
      phase space. We show that by modulating the energy distribution of the beam with
      two lasers, density modulation at the difference frequency of the two lasers can
      be generated after the beam passes through a chicane. In this experiment, density
      modulation around 10 THz was generated by down-converting the frequencies of an
      800 nm laser and a 1550 nm laser. The central frequency of the density modulation
      can be tuned by varying the laser wavelengths, beam energy chirp, or momentum
      compaction of the chicane. This technique can be applied to accelerator-based
      light sources for generation of coherent THz radiation and marks a significant
      advance toward tunable narrow band THz sources.

PMID- 23006376
TI  - Magnetically driven flows in arched plasma structures.
AB  - Laboratory experiments demonstrate high-speed plasma flows from both footpoints
      of arched magnetic flux tubes, resulting in bulk plasma transport into the flux
      tube and persistent axial collimation even as the flux tube lengthens and kinks.
      The measured flows are in agreement with the predictions of hoop force and
      collimation models involving fundamental MHD forces. These forces are expected to
      drive plasma acceleration in other open flux configurations with arched
      geometries, such as those found on the solar surface.

PMID- 23006377
TI  - Plasma adiabatic lapse rate.
AB  - The plasma analog of an adiabatic lapse rate (or temperature variation with
      height) in atmospheric physics is obtained. A new source of plasma temperature
      gradient in a binary ion species mixture is found that is proportional to the
      concentration gradient ?alpha and difference in average ionization states Z(2)
      Z(1). Application to inertial-confinement-fusion implosions indicates a
      potentially strong effect in plastic (CH) ablators that is not modeled with
      mainline (single-fluid) simulations. An associated plasma thermodiffusion
      coefficient is derived, and charge-state diffusion in a single-species plasma is
      also predicted.

PMID- 23006378
TI  - Adiabatic-nonadiabatic transition in warm long-range interacting systems: the
      transport of intense inhomogeneous beams.
AB  - We investigate the role of the temperature in the onset of singularities and the
      consequent breakdown in a macroscopic fluid model for long-range interacting
      systems. In particular, we consider an adiabatic fluid description for the
      transport of intense inhomogeneous charged particle beams. We find that there
      exists a critical temperature below which the fluid model always develops a
      singularity and breaks down as the system evolves. As the critical temperature is
      approached, however, the time for the occurrence of the singularity diverges.
      Therefore, the critical temperature separates two distinct dynamical phases: a
      nonadiabatic transport at lower temperatures and a completely adiabatic evolution
      at higher temperatures. These findings are verified with the aid of self
      consistent N-particle simulations.

PMID- 23006379
TI  - Drive asymmetry and the origin of turbulence in an ICF implosion.
AB  - 2D and 3D numerical simulations with the adaptive mesh refinement Eulerian
      radiation-hydrocode RAGE at unprecedented spatial resolution are used to
      investigate the connection between drive asymmetry and the generation of
      turbulence in the DT fuel in a simplified inertial-confinement fusion (ICF)
      implosion. Long-wavelength deviations from spherical symmetry in the pressure
      drive lead to the generation of coherent vortical structures in the DT gas and it
      is the three-dimensional instability of these structures that in turn leads to
      turbulence and mix. The simulations suggest that this mechanism may be an
      additional important source of mix in ICF implosions. Applications to target
      ignition at the National Ignition Facility are briefly discussed.

PMID- 23006380
TI  - Confinement-driven phase separation of quantum liquid mixtures.
AB  - We report small-angle neutron scattering studies of liquid helium mixtures
      confined in Mobil Crystalline Material-41 (MCM-41), a porous silica glass with
      narrow cylindrical nanopores (d=3.4 nm). MCM-41 is an ideal model adsorbent for
      fundamental studies of gas sorption in porous media because its monodisperse
      pores are arranged in a 2D triangular lattice. The small-angle scattering
      consists of a series of diffraction peaks whose intensities are determined by how
      the imbibed liquid fills the pores. Pure (4)He adsorbed in the pores show
      classic, layer-by-layer film growth as a function of pore filling, leaving the
      long range symmetry of the system intact. In contrast, the adsorption of (3)He
      (4)He mixtures produces a structure incommensurate with the pore lattice. Neither
      capillary condensation nor preferential adsorption of one helium isotope to the
      pore walls can provide the symmetry-breaking mechanism. The scattering is
      consistent with the formation of randomly distributed liquid-liquid microdomains
      ~2.3 nm in size, providing evidence that confinement in a nanometer scale
      capillary can drive local phase separation in quantum liquid mixtures.

PMID- 23006381
TI  - p-Wave polaron.
AB  - We consider a single impurity immersed in a Fermi sea close to an interspecies p
      wave Feshbach resonance. We calculate its dispersion and spectral response to a
      radio frequency pulse. In a magnetic field, dipolar interactions split the
      resonance and two novel features with respect to the s-wave case appear: a third
      polaron branch in the excitation spectrum, in addition to the usual attractive
      and repulsive ones; and an anisotropic dispersion of the impurity characterized
      by different effective masses perpendicular and parallel to the magnetic field.
      The anisotropy can be tuned as a function of the field strength and the two
      effective masses may have opposite signs, or become smaller than the bare mass.

PMID- 23006382
TI  - Pressure-driven evolution of the covalent network in CaB6.
AB  - We synthesized and solved an unexpectedly complex crystal structure of CaB(6)
      under high pressures (up to 44 GPa) and temperatures. The only known crystal
      structure in the large family of metal hexaborides, a simple cubic cP7 type
      discovered over 80 years ago, is shown here to transform into a tetragonal tI56
      configuration comprised of unfamiliar 24-atom boron units. The interpretation of
      the convoluted x-ray diffraction pattern was accomplished with an ab initio
      evolutionary search which identified the tI56 structure (28 atoms per primitive
      unit cell) without any parameter input. The exotic CaB(6) phase was successfully
      quenched down to ambient pressure.

PMID- 23006383
TI  - Planar defect nucleation and annihilation mechanisms in nanocontact plasticity of
      metal surfaces.
AB  - The incipient contact plasticity of metallic surfaces involves nucleation of
      crystalline defects. The present molecular dynamics simulations and
      nanoindentation experiments demonstrate that the current notion of nanocontact
      plasticity in fcc metals does not apply to high-strength bcc metals. We show that
      nanocontact plasticity in Ta-a model bcc metal-is triggered by thermal and
      loading-rate dependent (dynamic) nucleation of planar defects such as twins and
      unique {011} stacking fault bands. Nucleation of different planar defects
      depending on surface orientation leads to distinct signatures (pop ins) in the
      nanoindentation curves. Nanoscale plasticity is then ruled by an outstanding
      dynamical mechanism governing twin annihilation and subsequent emission of linear
      defects (full dislocations). While this investigation concerns Ta crystals, the
      present are landmark findings for other model bcc metals.

PMID- 23006384
TI  - Non-Arrhenius ionic conductivities in glasses due to a distribution of activation
      energies.
AB  - Previously observed non-Arrhenius behavior in fast ion conducting glasses [J.
      Kincs and S. W. Martin, Phys. Rev. Lett. 76, 70 (1996)] occurs at temperatures
      near the glass transition temperature, T(g), and is attributed to changes in the
      ion mobility due to ion trapping mechanisms that diminish the conductivity and
      result in a decreasing conductivity with increasing temperature. It is intuitive
      that disorder in glass will also result in a distribution of the activation
      energies (DAE) for ion conduction, which should increase the conductivity with
      increasing temperature, yet this has not been identified in the literature. In
      this Letter, a series of high precision ionic conductivity measurements are
      reported for 0.5Na(2)S + 0.5[xGeS(2) + (1-x)PS(5/2)] glasses with compositions
      ranging from 0 <= x <= 1. The impact of the cation site disorder on the
      activation energy is identified and explained using a DAE model. The absence of
      the non-Arrhenius behavior in other glasses is explained and it is predicted
      which glasses are expected to accentuate the DAE effect on the ionic
      conductivity.

PMID- 23006359
TI  - Evidence for a particle produced in association with weak bosons and decaying to
      a bottom-antibottom quark pair in higgs boson searches at the tevatron.
AB  - We combine searches by the CDF and D0 Collaborations for the associated
      production of a Higgs boson with a W or Z boson and subsequent decay of the Higgs
      boson to a bottom-antibottom quark pair. The data, originating from Fermilab
      Tevatron pp collisions at ?s = 1.96 TeV, correspond to integrated luminosities of
      up to 9.7 fb(-1). The searches are conducted for a Higgs boson with mass in the
      range 100-150 GeV/c(2). We observe an excess of events in the data compared with
      the background predictions, which is most significant in the mass range between
      120 and 135 GeV/c(2). The largest local significance is 3.3 standard deviations,
      corresponding to a global significance of 3.1 standard deviations. We interpret
      this as evidence for the presence of a new particle consistent with the standard
      model Higgs boson, which is produced in association with a weak vector boson and
      decays to a bottom-antibottom quark pair.

PMID- 23006385
TI  - n-type doping of germanium from phosphine: early stages resolved at the atomic
      level.
AB  - To understand the atomistic doping process of phosphorus in germanium, we present
      a combined scanning tunneling microscopy, temperature programed desorption, and
      density functional theory study of the reactions of phosphine with the Ge(001)
      surface. Combining experimental and theoretical results, we demonstrate that
      PH(2) + H with a footprint of one Ge dimer is the only product of room
      temperature chemisorption. Further dissociation requires thermal activation. At
      saturation coverage, PH(2) + H species self-assemble into ordered patterns
      leading to phosphorus coverages of up to 0.5 monolayers.

PMID- 23006386
TI  - Measurement of the binding energies of the organic-metal perylene-teracarboxylic
      dianhydride/Au111 bonds by molecular manipulation using an atomic force
      microscope.
AB  - Based on single molecule manipulation experiments in a combined scanning
      tunneling microscope/frequency modulated atomic force microscope, we quantify the
      individual binding energy contributions to an organic-metal bond experimentally.
      The method allows the determination of contributions from, e.g., local chemical
      bonds, metal-molecule hybridization, and van der Waals interactions, as well as
      the total adsorption energy.

PMID- 23006387
TI  - Double exchange ferromagnetism in the Peierls insulator state.
AB  - We study the effects of opening the band gap on the double exchange
      ferromagnetism. Applying the density-matrix renormalization group method and an
      analytical expansion from the dimer limit to the one-dimensional double exchange
      model, we demonstrate for a relevant region of the exchange coupling that, in the
      weak dimerization regime, the Peierls gap opens in the fully spin-polarized
      conduction band without affecting its ferromagnetism, whereas in the strong
      dimerization regime, the ferromagnetism is destroyed, and the Mott gap opens
      instead, leading the system to the antiferromagnetic quasi-long-range order. An
      insulator version of double exchange ferromagnetism is thus established.

PMID- 23006388
TI  - Singular behavior of eigenstates in Anderson's model of localization.
AB  - We observe an apparent singularity in the electronic properties of the Anderson
      model of localization with bounded diagonal disorder, which is clearly distinct
      from the well-established mobility edge (localization-delocalization transition)
      that occurs in dimensions d > 2. We present results of numerical calculations for
      Anderson's original uniform (box) distribution of on-site disorder in dimensions
      d = 1, 2, and 3. To establish this hitherto unreported behavior, and to
      understand its evolution with disorder, we contrast the behavior of two different
      measures of the localization length of the electronic wave functions-the averaged
      inverse participation ratio and the Lyapunov exponent. Our data suggest that
      Anderson's model exhibits richer behavior than has been established so far.

PMID- 23006389
TI  - Detection of electrically modulated inverse spin hall effect in an Fe/GaAs
      microdevice.
AB  - We report the detection of the inverse spin Hall effect (ISHE) in n-gallium
      arsenide (n-GaAs) combined with electrical injection and modulation of the spin
      current. We use epitaxial ultrathin-Fe/GaAs injection contacts with strong in
      plane magnetic anisotropy. This allows us to simultaneously perform Hanle spin
      precession measurements on an Fe detection electrode and ISHE measurements in an
      applied in-plane hard-axis magnetic field. In this geometry, we can
      experimentally separate the ordinary from the spin-Hall signals. Electrical spin
      injection and detection are combined in our microdevice with an applied
      electrical drift current to modulate the spin distribution and spin current in
      the channel. The magnitudes and external field dependencies of the signals are
      quantitatively modeled by solving drift-diffusion and Hall-cross response
      equations.

PMID- 23006390
TI  - Spin-filter tunnel junction with matched fermi surfaces.
AB  - Efficient injection of spin-polarized current into a semiconductor is a basic
      prerequisite for building semiconductor-based spintronic devices. Here, we use
      inelastic electron tunneling spectroscopy to show that the efficiency of spin
      filter-type spin injectors is limited by spin scattering of the tunneling
      electrons. By matching the Fermi-surface shapes of the current injection source
      and target electrode material, spin injection efficiency can be significantly
      increased in epitaxial ferromagnetic insulator tunnel junctions. Our results
      demonstrate that not only structural but also Fermi-surface matching is important
      to suppress scattering processes in spintronic devices.

PMID- 23006391
TI  - Tuning the performance of organic spintronic devices using x-ray generated traps.
AB  - X rays produced during electron-beam deposition of metallic electrodes
      drastically change the performance of organic spintronic devices. The x rays
      generate traps with an activation energy of ~0.5  eV in a commonly used organic.
      These traps lead to a dramatic decrease in spin-diffusion length in organic spin
      valves. In organic magnetoresistive (OMAR) devices, however, the traps strongly
      enhance magnetoresistance. OMAR is an intrinsic magnetotransport phenomenon and
      does not rely on spin injection. We discuss our observations in the framework of
      currently existing theories.

PMID- 23006392
TI  - Topological character and magnetism of the Dirac state in Mn-doped Bi2Te3.
AB  - First-principles and model calculations show that the Dirac surface state of the
      topological insulator Bi(2)Te(3) survives upon moderate Mn doping of the surface
      layers but can lose its topological character as a function of magnetization
      direction. The dispersion depends considerably on the direction of the Mn
      magnetization: for perpendicular magnetization, a gap of 16 meV opens up at the
      Dirac point; for in-plane magnetization, a tiny gap can be opened or closed in
      dependence on the magnetization azimuth. The ground state is ferromagnetic, with
      a critical temperature of 12 K. The results provide a path towards a magnetic
      control of the topological character of the Dirac surface state and its
      consequences to spin-dependent transport properties.

PMID- 23006393
TI  - Stabilizing the zigzag edge: graphene nanoribbons with sterically constrained
      terminations.
AB  - The zigzag edge of a graphene nanoribbon is predicted to support a spin-polarized
      edge state. However, this edge state only survives under a pure sp(2)
      termination, and it is difficult to produce thermodynamic conditions that favor a
      pure sp(2) termination of a graphene edge, since the edge carbons generally
      prefer to bond to two hydrogen atoms in sp(3) hybridization, rather than one
      hydrogen, as sp(2). We describe how to use the steric effects of large, bulky
      ligands to modify the thermodynamics of edge termination and favor the sp(2) edge
      during, e.g., chemical vapor deposition. Ab initio calculations demonstrate that
      these alternative terminations can support robust edge states across a broad
      range of thermodynamic conditions. This method of exploiting steric crowding
      effects along the one-dimensional edge of a two-dimensional system may be a
      general way to control edge reconstructions across a range of emerging single
      layer systems.

PMID- 23006394
TI  - Probing the role of co substitution in the electronic structure of iron
      pnictides.
AB  - The role of Co substitution in the low-energy electronic structure of
      Ca(Fe(0.944)Co(0.056))(2)As(2) is investigated by resonant photoemission
      spectroscopy and density-functional theory. The Co 3d state center of mass is
      observed at 250 meV higher binding energy than that of Fe, indicating that Co
      possesses one extra valence electron and that Fe and Co are in the same oxidation
      state. Yet, significant Co character is detected for the Bloch wave functions at
      the chemical potential, revealing that the Co 3d electrons are part of the Fermi
      sea determining the Fermi surface. This establishes the complex role of Co
      substitution in CaFe(2)As(2) and the inadequacy of a rigid-band shift
      description.

PMID- 23006362
TI  - J/psi suppression at forward rapidity in Pb-Pb collisions at ?s(NN) = 2.76 TeV.
AB  - The ALICE experiment has measured the inclusive J/psi production in Pb-Pb
      collisions at ?s(NN) = 2.76 TeV down to zero transverse momentum in the rapidity
      range 2.5 < y < 4. A suppression of the inclusive J/psi yield in Pb-Pb is
      observed with respect to the one measured in pp collisions scaled by the number
      of binary nucleon-nucleon collisions. The nuclear modification factor, integrated
      over the 0%-80% most central collisions, is 0.545 +/- 0.032(stat) +/- 0.083(syst)
      and does not exhibit a significant dependence on the collision centrality. These
      features appear significantly different from measurements at lower collision
      energies. Models including J/psi production from charm quarks in a deconfined
      partonic phase can describe our data.

PMID- 23006395
TI  - Berezinskii-Kosterlitz-Thouless transition to the superconducting state of heavy
      fermion superlattices.
AB  - We propose an explanation of the superconducting transitions discovered in the
      heavy-fermion superlattices by Mizukami et al. [Nature Phys. 7, 849 (2011)] in
      terms of Berezinskii-Kosterlitz-Thouless (BKT) transition. We observe that the
      effective mass mismatch between the heavy-fermion superconductor and the normal
      metal regions provides an effective barrier that enables quasi-2D
      superconductivity in such systems. We show that the resistivity data, both with
      and without magnetic field, are consistent with BKT transition. Furthermore, we
      study the influence of a nearby magnetic quantum critical point on the vortex
      system and find that the vortex core energy can be significantly reduced due to
      magnetic fluctuations. Further reduction of the gap with decreasing number of
      layers is understood as a result of pair breaking effect of Yb ions at the
      interface.

PMID- 23006396
TI  - Spin reorientation in TlFe1.6Se2 with complete vacancy ordering.
AB  - The relationship between vacancy ordering and magnetism in TlFe(1.6)Se(2) has
      been investigated via single crystal neutron diffraction, nuclear forward
      scattering, and transmission electron microscopy. The examination of chemically
      and structurally homogeneous crystals allows the true ground state to be
      revealed, which is characterized by Fe moments lying in the ab plane below 100 K.
      This is in sharp contrast to crystals containing regions of order and disorder,
      where a competition between c axis and ab plane orientations of the moments is
      observed. The properties of partially disordered TlFe(1.6)Se(2) are, therefore,
      not associated with solely the ordered or disordered regions. This contrasts the
      viewpoint that phase separation results in independent physical properties in
      intercalated iron selenides, suggesting a coupling between ordered and disordered
      regions may play an important role in the superconducting analogues.

PMID- 23006397
TI  - Magnetic susceptibility of collinear and noncollinear heisenberg
      antiferromagnets.
AB  - Predictions of the anisotropic magnetic susceptibility chi below the
      antiferromagnetic (AFM) ordering temperatures T(N) of local moment Heisenberg
      AFMs have been made previously using molecular field theory (MFT) but are very
      limited in their applicability. Here a MFT calculation of chi(T <= T(N)) is
      presented for a wide variety of collinear and noncollinear Heisenberg AFMs
      containing identical crystallographically equivalent spins without recourse to
      magnetic sublattices. The results are expressed in terms of directly measurable
      experimental parameters and are fitted with no adjustable parameters to
      experimental chi(T <= T(N)) data from the literature for several collinear and
      noncollinear AFMs. The influence of spin correlations and fluctuations beyond MFT
      is quantified by the deviation of the theory from the data. The origin of the
      universal chi(T <= T(N)) observed for triangular lattice AFMs exhibiting coplanar
      noncollinear 120 degrees  AFM ordering is clarified.

PMID- 23006398
TI  - Detection and in situ switching of unreversed interfacial antiferromagnetic spins
      in a perpendicular-exchange-biased system.
AB  - By using the perpendicular-exchange-biased Pt/Co/alpha-Cr(2)O(3) system, we
      provide experimental evidence that the unreversed uncompensated Cr spins exist at
      the Co/alpha-Cr(2)O(3) interface. The unreversed uncompensated Cr spin manifests
      itself in both the vertical shift of an element-specific magnetization curve and
      the relative peak intensity of soft-x-ray magnetic circular dichroism spectrum.
      We also demonstrate an in situ switching of the interfacial Cr spins and
      correspondingly a reversal of the exchange bias without interfacial atomic
      diffusion. Such switching shows the direct relationship between the interfacial
      antiferromagnetic spins and origin of the exchange bias. The demonstrated
      switching of exchange bias would likely offer a new design of advanced
      spintronics devices, using the perpendicular-exchange-biased system, with low
      power consumption and ultrafast operation.

PMID- 23006399
TI  - Pressure and temperature control of spin-switchable metal-organic coordination
      polymers from ab initio calculations.
AB  - We explore a combination of density-functional theory with supplemented Coulomb U
      (DFT+U) and ab initio molecular dynamics simulations to investigate the spin
      crossover (SCO) phenomenon in coordination polymers. We demonstrate the
      applicability of the method for the case of bimetallic metal-organic framework
      Fe(2)[Nb(CN)(8)].(4-pyridinealdoxime)(8).2H(2)O [see S. Ohkoshi et al. Nat. Chem.
      3, 564 (2011)]. Our study shows that this approach is capable of capturing the
      SCO transitions driven by pressure as well as temperature. In addition to
      discovering novel spin-state transitions, magnetic states involving changes in
      the long-range magnetic ordering pattern are achieved, thereby offering the
      tunability of spin states as well as the long-range order of the spins. We
      compare the SCO transition in the Fe-based framework with a computer designed Mn
      based variant.

PMID- 23006400
TI  - Quantum order by disorder and accidental soft mode in Er2Ti2O7.
AB  - Motivated by recent neutron scattering experiments, we derive and study an
      effective "pseudodipolar" spin-1/2 model for the XY pyrochlore antiferromagnet
      Er(2)Ti(2)O(7). While a bond-dependent in-plane exchange anisotropy removes any
      continuous symmetry, it does lead to a one-parameter 'accidental' classical
      degeneracy. This degeneracy is lifted by quantum fluctuations in favor of the
      noncoplanar spin structure observed experimentally-a rare experimental instance
      of quantum order by disorder. A non-Goldstone low-energy mode is present in the
      excitation spectrum in accordance with inelastic neutron scattering data. Our
      theory also resolves the puzzle of the experimentally observed continuous
      ordering transition, absent from previous models.

PMID- 23006401
TI  - Quantum spin liquids and the metal-insulator transition in doped semiconductors.
AB  - We describe a new possible route to the metal-insulator transition in doped
      semiconductors such as Si:P or Si:B. We explore the possibility that the loss of
      metallic transport occurs through Mott localization of electrons into a quantum
      spin liquid state with diffusive charge neutral "spinon" excitations. Such a
      quantum spin liquid state can appear as an intermediate phase between the metal
      and the Anderson-Mott insulator. An immediate testable consequence is the
      presence of metallic thermal conductivity at low temperature in the electrical
      insulator near the metal-insulator transition. Further, we show that though the
      transition is second order, the zero temperature residual electrical conductivity
      will jump as the transition is approached from the metallic side. However, the
      electrical conductivity will have a nonmonotonic temperature dependence that may
      complicate the extrapolation to zero temperature. Signatures in other experiments
      and some comparisons with existing data are made.

PMID- 23006402
TI  - Photon-assisted tunneling through self-assembled InAs quantum dots in the
      terahertz frequency range.
AB  - We have investigated terahertz (THz) photon-assisted tunneling in single self
      assembled InAs quantum dots (QDs). Two types of photon-assisted tunneling
      processes have been observed in the THz range: ground state resonance and photon
      induced excited state resonance, depending on the relative magnitude between the
      orbital quantization energy of the QDs and the THz photon energy. Furthermore, we
      could realize a very high coupling efficiency between THz waves and QDs and
      observed multiphoton absorption up to the fourth-order during the tunneling
      process, resulting in almost complete lifting of the Coulomb blockade.

PMID- 23006403
TI  - Bond flexibility and low valence promote finite clusters of self-aggregating
      particles.
AB  - Systems of complex particles such as proteins or colloidal particles have a
      widely observed tendency to form nonconnected nanometer-size clusters at steady
      state, but the underlying mechanisms remain poorly understood. We report here a
      numerical study on the self-aggregation of low-valence particles with flexible
      bonds (i.e., free bond orientations) in two dimensions and predict the formation
      of a stable cluster phase for average valences ranging from 2 to 3.6. For the
      intermediate case of trivalent particles, we show that a cluster phase is present
      over a wide range of concentrations and interaction energies. The clusters are
      polydisperse in size, have a fractal dimension of 1.5, and tend to fully saturate
      their bonds at high interaction energies. The number of unformed bonds scales
      linearly with the number of particles in a cluster, which implies the absence of
      phase transition in the explored region of interaction energies and
      concentrations. We discuss possible implications of our model for membrane
      protein clustering.

PMID- 23006404
TI  - Stiffness of the extrafibrillar phase in staggered biological arrays.
AB  - A number of important biological tissues such as nacre, tendon, and bone consist
      of staggered structural arrays as universal motifs. Such arrays usually include
      stiff fibril-like (or plateletlike, or needlelike) elements embedded in an
      extrafibrillar (XF) phase. This work discusses the effect of the stiffness of
      such an XF matrix on the elastic properties of the resulting staggered composite.
      In the case of most biological composites, this XF stiffness is hardly accessible
      and very little data are available. We develop an analysis based on previous
      analytical formulation that results in a relation between the XF modulus and the
      deformations of the staggered particles. This analysis is then used to back
      calculate the yet unmeasured modulus of the XF phase from experimental
      deformation data, thereby providing a simple alternative to potentially complex
      direct measurements. This is demonstrated and validated for parallel-fiber bone
      tissue.

PMID- 23006405
TI  - Physarum polycephalum percolation as a paradigm for topological phase transitions
      in transportation networks.
AB  - We study the formation of transportation networks of the true slime mold Physarum
      polycephalum after fragmentation by shear. Small fragments, called
      microplasmodia, fuse to form macroplasmodia in a percolation transition. At this
      topological phase transition, one single giant component forms, connecting most
      of the previously isolated microplasmodia. Employing the configuration model of
      graph theory for small link degree, we have found analytically an exact solution
      for the phase transition. It is generally applicable to percolation as seen,
      e.g., in vascular networks.

PMID- 23006406
TI  - Defense mechanisms of empathetic players in the spatial ultimatum game.
AB  - Experiments on the ultimatum game have revealed that humans are remarkably fond
      of fair play. When asked to share an amount of money, unfair offers are rare and
      their acceptance rate small. While empathy and spatiality may lead to the
      evolution of fairness, thus far considered continuous strategies have precluded
      the observation of solutions that would be driven by pattern formation. Here we
      introduce a spatial ultimatum game with discrete strategies, and we show that
      this simple alteration opens the gate to fascinatingly rich dynamical behavior.
      In addition to mixed stationary states, we report the occurrence of traveling
      waves and cyclic dominance, where one strategy in the cycle can be an alliance of
      two strategies. The highly webbed phase diagram, entailing continuous and
      discontinuous phase transitions, reveals hidden complexity in the pursuit of
      human fair play.

PMID- 23006407
TI  - Comment on "Impact of a global quadratic potential on galactic rotation curves".

PMID- 23006408
TI  - Comment on "Dynamic opinion model and invasion percolation".

PMID- 23006410
TI  - Role of Serine140 in the mode of action of Mycobacterium tuberculosis beta
      ketoacyl-ACP Reductase (MabA).
AB  - BACKGROUND: Tuberculosis (TB) still remains one of the most deadly infectious
      diseases in the world. Mycobacterium tuberculosis beta-ketoacyl-ACP Reductase
      (MabA) is a member of the fatty acid elongation system type II, providing
      precursors of mycolic acids that are essential to the bacterial cell growth and
      survival. MabA has been shown to be essential for M. tuberculosis survival and to
      play a role in intracellular signal transduction of bacilli. FINDINGS: Here we
      describe site-directed mutagenesis, recombinant protein expression and
      purification, steady-state kinetics, fluorescence spectroscopy, and molecular
      modeling for S140T and S140A mutant MabA enzymes. No enzyme activity could be
      detected for S140T and S140A. Although the S140T protein showed impaired NADPH
      binding, the S140A mutant could bind to NADPH. Computational predictions for
      NADPH binding affinity to WT, S140T and S140A MabA proteins were consistent with
      fluorescence spectroscopy data. CONCLUSIONS: The results suggest that the main
      role of the S140 side chain of MabA is in catalysis. The S140 side chain appears
      to also play an indirect role in NADPH binding. Interestingly, NADPH titrations
      curves shifted from sigmoidal for WT to hyperbolic for S140A, suggesting that the
      S140 residue may play a role in displacing the pre-existing equilibrium between
      two forms of MabA in solution. The results here reported provide a better
      understanding of the mode of action of MabA that should be useful to guide the
      rational (function-based) design of inhibitors of MabA enzyme activity which,
      hopefully, could be used as lead compounds with anti-TB action.

PMID- 23006411
TI  - The effect of 12 weeks of aerobic, resistance or combination exercise training on
      cardiovascular risk factors in the overweight and obese in a randomized trial.
AB  - BACKGROUND: Evidence suggests that exercise training improves CVD risk factors.
      However, it is unclear whether health benefits are limited to aerobic training or
      if other exercise modalities such as resistance training or a combination are as
      effective or more effective in the overweight and obese. The aim of this study is
      to investigate whether 12 weeks of moderate-intensity aerobic, resistance, or
      combined exercise training would induce and sustain improvements in
      cardiovascular risk profile, weight and fat loss in overweight and obese adults
      compared to no exercise. METHODS: Twelve-week randomized parallel design
      examining the effects of different exercise regimes on fasting measures of
      lipids, glucose and insulin and changes in body weight, fat mass and dietary
      intake. Participants were randomized to either: Group 1 (Control, n = 16); Group
      2 (Aerobic, n = 15); Group 3 (Resistance, n = 16); Group 4 (Combination, n = 17).
      Data was analysed using General Linear Model to assess the effects of the groups
      after adjusting for baseline values. Within-group data was analyzed with the
      paired t-test and between-group effects using post hoc comparisons. RESULTS:
      Significant improvements in body weight (-1.6%, p = 0.044) for the Combination
      group compared to Control and Resistance groups and total body fat compared to
      Control (-4.4%, p = 0.003) and Resistance (-3%, p = 0.041). Significant
      improvements in body fat percentage (-2.6%, p = 0.008), abdominal fat percentage
      (-2.8%, p = 0.034) and cardio-respiratory fitness (13.3%, p = 0.006) were seen in
      the Combination group compared to Control. Levels of ApoB48 were 32% lower in the
      Resistance group compared to Control (p = 0.04). CONCLUSION: A 12-week training
      program comprising of resistance or combination exercise, at moderate-intensity
      for 30 min, five days/week resulted in improvements in the cardiovascular risk
      profile in overweight and obese participants compared to no exercise. From our
      observations, combination exercise gave greater benefits for weight loss, fat
      loss and cardio-respiratory fitness than aerobic and resistance training
      modalities. Therefore, combination exercise training should be recommended for
      overweight and obese adults in National Physical Activity Guidelines.This
      clinical trial was registered with the Australian New Zealand Clinical Trials
      Registry (ANZCTR), registration number: ACTRN12609000684224.

PMID- 23006412
TI  - Analysis of T-DNA integration and generative segregation in transgenic winter
      triticale  (x Triticosecale Wittmack).
AB  - BACKGROUND: While the genetic transformation of the major cereal crops has become
      relatively routine, to date only a few reports were published on transgenic
      triticale, and robust data on T-DNA integration and segregation have not been
      available in this species. RESULTS: Here, we present a comprehensive analysis of
      stable transgenic winter triticale cv. Bogo carrying the selectable marker gene
      HYGROMYCIN PHOSPHOTRANSFERASE (HPT) and a synthetic green fluorescent protein
      gene (gfp). Progeny of four independent transgenic plants were comprehensively
      investigated with regard to the number of integrated T-DNA copies, the number of
      plant genomic integration loci, the integrity and functionality of individual T
      DNA copies, as well as the segregation of transgenes in T1 and T2 generations,
      which also enabled us to identify homozygous transgenic lines. The truncation of
      some integrated T-DNAs at their left end along with the occurrence of independent
      segregation of multiple T-DNAs unintendedly resulted in a single-copy segregant
      that is selectable marker-free and homozygous for the gfp gene. The heritable
      expression of gfp driven by the maize UBI-1 promoter was demonstrated by confocal
      laser scanning microscopy. CONCLUSIONS: The used transformation method is a
      valuable tool for the genetic engineering of triticale. Here we show that
      comprehensive molecular analyses are required for the correct interpretation of
      phenotypic data collected from the transgenic plants.

PMID- 23006413
TI  - Screening for dietary fat intake of grade six children: self-assessment vs.
      maternal assessment.
AB  - As part of justifiable nutrition promotion, this study aimed to determine
      internal consistency of a dietary fat screener and to compare self-assessment to
      maternal assessment of fat intake of grade six (about 12 years old) learners in a
      South African public primary school. The children completed in school a
      pictorial, quantitative food frequency-type screener consisting of 10 high-fat
      food categories; mothers individually completed a text version. Internal
      consistency was measured with item-total correlations, Cronbach's alpha and the
      split-half method. Child-mother comparison was based on kappa (kappa) statistics,
      McNemar's tests, Wilcoxon signed-rank test and the Bland-Altman method. In total,
      101 (93.5%) children and 78 (72.2%) mothers responded. The screener was
      internally consistent, regardless of data source and statistical technique. For
      portion sizes and frequency of intake, children consistently reported higher
      intake than mothers. This resulted in systematic error, also evidenced by a
      significant difference from zero for the difference between child's and mother's
      final test scores for the whole group, and for boys and girls separately (always
      P < 0.001). In 76% of the pairs, classification into high fat or prudent intake
      was identical, yet the chance-corrected agreement was poor (kappa = 0.16) and non
      agreement was non-symmetrical (P = 0.001). Children and mothers reported high fat
      intakes (93% and 75%, respectively). It was concluded that the dietary fat
      screener was internally consistent, yet children and mothers did not agree in
      their assessment. The high fat intakes reported by children and mothers warrant
      measurement refinement and implementation of primary prevention programmes. 

PMID- 23006415
TI  - Permanent genetic resources added to Molecular Ecology Resources Database 1 June
      2012-31 July 2012.
AB  - This article documents the addition of 96 microsatellite marker loci to the
      Molecular Ecology Resources Database. Loci were developed for the following
      species: Clarias batrachus, Marmota himalayana, Schizothorax richardsonii,
      Sitophilus zeamais and Syagrus romanzoffiana. These loci were cross-tested on the
      following species: Clarias dussumeri, Clarias gariepinus, Heteropneustus
      fossilis, Sitophilus granarius and Sitophilus oryzae.

PMID- 23006414
TI  - Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression.
AB  - Langerhans cell sarcoma is a rare and aggressive high grade hematopoietic
      neoplasm with a dismal prognosis. It has a unique morphological and immunotypic
      profile with a CD1a/ langerin/S100 + phenotype. T cell lineage markers except for
      CD4 in Langerhans cell sarcoma have not been documented previously. We report a
      case of 86 year-old male of Caucasian descent who presented with an enlarging
      right neck mass over 2 months with an underlying unknown cause of anemia.
      Computed tomography scan of the neck, chest and abdomen revealed generalized
      lymphadenopathy and mild splenomegaly suspicious for lymphoma. Diagnostic core
      biopsy performed on right neck mass revealed a possible T cell lymphoma with
      expression of T cell lineage specific marker CD3 but conclusive diagnosis could
      not be made due to insufficient core biopsy sample. Further excisional biopsy
      performed on a left inguinal node showed a hematopoietic neoplasm with features
      of Langerhans cell sarcoma with a focal cytoplasmic CD3 expression in 30-40% of
      the tumor cells. PCR for T cell receptor (TCR) gene rearrangement failed to
      demonstrate a clonal gene rearrangement in the tumor cells arguing against a T
      cell lineage transdifferentiation, suggesting an aberrant CD3 expression. To the
      best of our knowledge, this case represents the first report of Langerhans cell
      sarcoma with an aberrant cytoplasmic CD3 expression. VIRTUAL SLIDES:
      http://www.diagnosticpathology.diagnomx.eu/vs/2065486371761991.

PMID- 23006417
TI  - Hepatitis B core antibody in blood donor in Sistan-Balutuestan province of Iran.
AB  - BACKGROUND: Safety of blood donor is an important issue for a recipient of blood
      so all blood donors are to screened for viral such as HBV, HCV, and HIV.
      Nevertheless, infections sometime occur by blood and its products. OBJECTIVE:
      Because we haven't got any awareness about isolated Hbc Ab from a blood donor who
      presented of occults B hepatitis which can transmit infection to blood recipient,
      we decided to evaluate HbcAb in a blood donor in this province. MATERIALS AND
      METHODS: This is a cross-sectional study on a blood donor in Sistan-Balutuestan
      province in southeast of Iran in 2010. All individuals referred for blood
      donation recruited to this. After consent demographic data was recorded from each
      case, 5 ml blood sample was drawn and centrifuged to separate out the serum and
      then HbsAb, HbcAb was assayed. Data analyzed by SPSS 16 and frequency, chi-
      square test, and Fisher exact test was used and if P > 0.05 it was accented as
      significant association. RESULT: All individuals were men with age 55 10.5 years.
      The number of people who had free job was 149 (34.6%) and the number of people
      whose education level was diploma was 159 (36.9%). About 423 (98.1%) lived in
      urban areas. The mean weight of men was 76.6 13.7; about 259 (60.1%) men were
      married. A total of 22 (5.1%) had a positive smoking history. HBc Ab was positive
      in 87 (20.2%). Nearly all people had HBsAb titer more than 10 IU/L. CONCLUSION:
      This study showed that some of the blood donors had isolated HbcAb positive
      therefore we recommend HbcAb screening for blood donation.

PMID- 23006416
TI  - Olive oil intake and CHD in the European Prospective Investigation into Cancer
      and Nutrition Spanish cohort.
AB  - Olive oil is well known for its cardioprotective properties; however,
      epidemiological data showing that olive oil consumption reduces incident CHD
      events are still limited. Therefore, we studied the association between olive oil
      and CHD in the European Prospective Investigation into Cancer and Nutrition
      (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 %
      male), free of CHD events at baseline, recruited from five EPIC-Spain centres
      from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle
      information was collected using interview-administered questionnaires. Cox
      proportional regression models were used to assess the relationship between
      validated incident CHD events and olive oil intake (energy-adjusted quartiles and
      each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential
      confounders. During a 10.4-year follow-up, 587 (79 % male) CHD events were
      recorded. Olive oil intake was negatively associated with CHD risk after
      excluding dietary mis-reporters (hazard ratio (HR) 0.93; 95 % CI 0.87, 1.00 for
      each 10 g/d per 8368 kJ (2000 kcal) and HR 0.78; 95 % CI 0.59, 1.03 for upper v.
      lower quartile). The inverse association between olive oil intake (per 10 g/d per
      8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced
      CHD risk (P = 0.048)), in never/low alcohol drinkers (25 % reduced CHD risk (P <
      0.001)) and in virgin olive oil consumers (14 % reduced CHD risk (P = 0.072)). In
      conclusion, olive oil consumption was related to a reduced risk of incident CHD
      events. This emphasises the need to conserve the traditional culinary use of
      olive oil within the Mediterranean diet to reduce the CHD burden.

PMID- 23006418
TI  - Knowledge, attitude and practices on needle-stick and sharps injuries in tertiary
      care cardiac hospital: a survey.
AB  - AIMS: One of the potential hazards for health care workers (HCWs) is needle-stick
      and sharp injuries (NSSIs). The objective of the study was to assess the
      knowledge and attitude of health care workers about the NSSIs. SETTINGS AND
      DESIGN: This was a cross-sectional survey conducted in the tertiary care cardiac
      center. The participants were health care workers including doctors, nurses,
      technicians, and housekeeping staff from the different areas of the hospital.
      METHODS AND MATERIALS: This cross-sectional survey was conducted in the institute
      using a self-administered validated questionnaire. The participants consisted of
      a total of 190 HCWs namely doctors, nurses, technicians, and housekeeping staff.
      STATISTICAL ANALYSIS USED: Nil. RESULTS: Results showed maximum participant were
      in the age group of 20-30 years. 94.7% were aware about standard precautions.
      91.5% knew about the procedure for reporting of NSSIs. Only 50.2% HCWs gave
      correct answers regarding disease transmission through needle stick and sharp
      injury. The prevalence of NSSIs was highest among nurses (38.4%), and needle on
      the disposable syringe (76.9%) was the most common source of NSSIs. CONCLUSIONS:
      The survey revealed few gaps in the knowledge amongst HCWs about NSSIs like risks
      associated with needle-stick injuries and use of preventive measures,
      disassembling of needles prior to disposal. These gaps can be addressed by
      extensive education. As nurses were the most affected victim for the NSSIs, more
      emphasis should be given towards them for reducing the NSSIs.

PMID- 23006419
TI  - The mechanism underlying the differentiation of human umbilical cord-derived
      mesenchymal stem cells into myocardial cells induced by 5-azacytidine.
AB  - OBJECTIVE: To investigate the molecular mechanism underlying the differentiation
      of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) into myocardial
      cells induced by 5-azacytidine (5-aza), and to explore the expression and
      significance of DLL4-Notch signaling in this process. MATERIALS AND METHODS:
      hUCMSCs were isolated and purified from the umbilical cords of normal or cesarean
      term deliveries under sterile conditions. After treatment with 5-aza for 24 h,
      hUCMSCs was continued to culture, the expression of GATA4 and NKx2.5 at 4 weeks
      after induction, DLL4 and Notch1 mRNA at 1d, 3d, 5d, 7d after induction were
      detected. The expression of cardiac troponin I (cTnI) after 4 weeks was
      determined by immunocytochemistry. RESULTS: hUCMSCs treated with 5-aza were
      stained positively for cTnI 4 weeks after induction. The expression of Notch1 and
      DLL4 mRNA in the 5-aza-induced group was stable and significantly higher than
      that in the control group (mean Ct value for the Notch1 gene: 0.51 +/- 0.21 in
      the 5-aza-induced group vs. 7.85 +/- 0.35 in the control group; mean Ct value for
      the DLL4 gene: 1.60 +/- 0.49 in the 5-aza-induced group vs. 12.42 +/- 0.73 in the
      control group). Similar results were observed for Nkx2.5 and GATA4 genes. The
      expressions of Nkx2.5 and GATA4 mRNA in the 5-aza group were 4.72 +/- 0.58 and
      3.76 +/- 0.06 times higher than that in the control group, respectively, with
      statistical significance. CONCLUSIONS: hUCMSCs can be differentiated into
      myocardial cells by 5-aza induction in vitro. 5-Aza may affect this process by
      regulating the expression of GATA4 and Nkx2.5 genes. The DLL4-Notch signal
      pathway may be involved in this process.

PMID- 23006420
TI  - Association of protein C deficiency with heat stroke in cool environment.
AB  - Heat stroke in cool environmental conditions has been a rare occurrence. We
      describe a case of heat stroke occurring in cool conditions in a previously
      healthy male who on work up was detected to have underlying procoagulant state.

PMID- 23006421
TI  - IVC filter: review.
AB  - Thrombo-embolic disease continues to be the paramount cause of morbidity as well
      as mortality in those afflicted despite amelioration in diagnostic imaging and
      anticoagulation regimens. Sometimes, standard medical therapy for thrombo
      embolism is contraindicated, for it results in complications, or fails to
      adequately protect patients from pulmonary embolism (PE). These patients are
      treated by insertion of inferior vena cava (IVC) filters. Although IVC filters
      diminish long-term risk of pulmonary embolism (PE), they are associated with
      increased risk of IVC thrombosis and lower-extremity deep venous thrombosis (DVT)
      as compared to anticoagulation alone. Despite their prolonged use for more than
      40 years, there are limited randomized clinical trials, comparing oral
      anticoagulation with IVC filters. Also, data on long term use of IVC filter is
      scarce. This article will address traits of an ideal IVC filter, different types
      of filters available and complications involved in the use of the different IVC
      filter.

PMID- 23006422
TI  - Helicobacter pylori infection in India from a western perspective.
AB  - Helicobacter pylori is a common bacterial infectious disease whose manifestations
      predominately affect the gastrointestinal tract. India is the prototypical
      developing country as far as H. pylori infection is concerned and more than 20
      million Indians are estimated to suffer from peptic ulcer disease. Considering
      the high level of Medicine and of the pharmaceutical industry, one would expect
      that India would be the source of much needed information regarding new therapies
      and approaches that remain effective in the presence of antimicrobial resistance,
      new methods to reliably prevent reinfection, and the development of therapeutic
      and preventive vaccines. Here, we discuss H. pylori as an Indian problem with an
      emphasis on H. pylori infection as a serious transmissible infectious disease. We
      discuss the pros and cons of eradication of H. pylori from the entire population
      and come down on the side of eradication. The available data from India regarding
      antimicrobial use and resistance as well as the effectiveness of various
      treatments is discussed. Rigorous ongoing studies to provide current regional
      antibiotic resistance patterns coupled with data concerning the success rate with
      different treatment regimens are needed to guide therapy. A systematic approach
      to identify reliably effective (e.g., 90% or greater treatment success) cost
      effective regimens is suggested as well as details of regimens likely to be
      effective in India. H. pylori is just one of the health care problems faced in
      India, but one where all the resources are on hand to understand and solve it.

PMID- 23006424
TI  - Impact of geriatric conditions versus medical diagnoses on ADL disability among
      nonagenarians and centenarians.
AB  - OBJECTIVE: The authors investigated the relationship of activities of daily
      living (ADL) disability with medical diseases and geriatric conditions among
      nonagenarians and centenarians. METHOD: Cross-sectional, n = 870 Chinese (age
      range: 90-108 years). Self-reported medical diseases and geriatric-specific
      conditions were obtained by face-to-face interviews. Biomedical measurements
      included systolic/diastolic blood pressure, BMI (body mass index), albumin,
      fasting glucose, creatinine clearance, hemoglobin, and lipid panel. RESULTS: In
      bivariate analyses, 4 of 7 geriatric conditions (hearing problems, falls,
      cognitive impairment, fracture), and 6 of 11 biomedical measurements (fasting
      glucose, cholesterol, LDL, creatinine clearance, hemoglobin, albumin), but none
      of 10 medical diseases and no degree of comorbidities, were associated with ADL
      disability. In four different multivariate logistic regression models, two
      geriatric conditions (impaired cognition, fracture) were significant in three
      models, respiratory disease in one model, and fasting glucose in two models.
      DISCUSSION: This study emphasizes the importance of geriatric conditions and
      their association with ADL disability among the oldest-old adult population.

PMID- 23006423
TI  - Genetic association with overall survival of taxane-treated lung cancer patients 
      a genome-wide association study in human lymphoblastoid cell lines followed by a
      clinical association study.
AB  - BACKGROUND: Taxane is one of the first line treatments of lung cancer. In order
      to identify novel single nucleotide polymorphisms (SNPs) that might contribute to
      taxane response, we performed a genome-wide association study (GWAS) for two
      taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs),
      followed by genotyping of top candidate SNPs in 874 lung cancer patient samples
      treated with paclitaxel. METHODS: GWAS was performed using 1.3 million SNPs and
      taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs
      with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC)
      patients were analyzed by Cox regression model, followed by integrated SNP
      microRNA-expression association analysis in LCLs and siRNA screening of candidate
      genes in SCLC (H196) and NSCLC (A549) cell lines. RESULTS: 147 and 180 SNPs were
      associated with paclitaxel or docetaxel IC50s with p-values <10-4 in the LCLs,
      respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples
      identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient
      overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes
      within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall
      survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to
      paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of
      CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468.
      CONCLUSIONS: GWAS in an LCL model system, joined with clinical translational and
      functional studies, might help us identify genetic variations associated with
      overall survival of lung cancer patients treated paclitaxel.

PMID- 23006425
TI  - Social isolation, loneliness and health among older adults.
AB  - OBJECTIVE: To examine the relationship of social isolation, loneliness and health
      outcomes among older adults. METHODS: Using data from the Leave Behind
      Questionnaire of the Health and Retirement Study (2006 and 2008), (n = 11,825)
      several indicators of social isolation were scaled and the Hughes 3-Item
      Loneliness Scale was used. Two measures of health (self-rated health and mental
      health conditions) were examined using logistic regression. RESULTS: Loneliness
      and social isolation were not highly correlated with one another (r = 0.201, p =
      0.000). Loneliness was associated with higher odds of having a mental health
      problem (OR: 1.17; CI: [1.13, 1.21], p = 0.000); and isolation was associated
      with higher odds of reporting one's health as being fair/poor (OR:1.39; CI:
      [1.21, 1.59], p = 0.000). DISCUSSION: The results suggest that global measures of
      isolation, that fail to distinguish between social isolation and feelings of
      loneliness, may not detect the impact on physical and mental health in older
      adults.

PMID- 23006427
TI  - Intracardiac echocardiographic diagnosis of thrombus formation in the left atrial
      appendage: a complementary role to transesophageal echocardiography.
AB  - BACKGROUND: We sought to develop and validate an intracardiac echocardiography
      (ICE) imaging strategy for evaluation of left atrial (LA) appendage (LAA) anatomy
      and function to clarify equivocal findings of LAA thrombus with transesophageal
      echocardiography (TEE). METHODS: A total of 56 patients with ICE imaging of the
      LAA for thrombus evaluation before atrial fibrillation (AF) or ventricular
      tachycardia (VT) ablation were included for analysis. Serial views of the LAA
      were obtained for evaluating anatomic structures and flow as the ICE transducer
      was advanced from the right ventricular outflow tract to the pulmonary artery.
      ICE imaging of the LAA was selectively performed in 9 of 56 patients following
      equivocal findings of thrombus on TEE in order to evaluate the complementary role
      of ICE to TEE in the diagnosis of LAA thrombus. RESULTS: ICE imaging of the LAA
      in 56 patients with AF (n = 42) or VT (n = 14) measured the long-(5.0 +/- 1.0 cm)
      and short-axis dimension (1.8 +/- 0.5 cm), and peak emptying flow velocity (50 +/
      23 cm/s). Of 56 patients, 47 had ICE imaging of LAA with no thrombus. In the
      remaining 9 patients, 6 had "equivocal" LAA thrombus on TEE, with 3 of these 6
      showing marked spontaneous echo contrast (SEC), whereas ICE detected one patient
      with LAA thrombus and the other 5 without thrombus (two with severe SEC/sluggish
      flow); the remaining 3 had "high suspicion" for thrombus detected by TEE, whereas
      ICE detected only one with LAA thrombus. Based on ICE diagnosis, two patients
      with LAA thrombus had the procedure cancelled, and all others had successful
      completion of the scheduled procedures. CONCLUSION: ICE can provide serial
      assessment, multiple views, and detailed imaging of the LAA to reliably diagnose
      the presence of thrombus. Our findings support the use of ICE when equivocal TEE
      findings require confirmation prior to electrophysiological procedures.

PMID- 23006426
TI  - Depressive symptoms and memory performance among older adults: results from the
      ACTIVE memory training intervention.
AB  - BACKGROUND: Cognitive performance benefits from the Advanced Cognitive Training
      for Independent and Vital Elderly (ACTIVE) study may differ for individuals who
      exhibit a greater number of depressive symptoms. METHOD: Using data from ACTIVE
      memory training and control conditions, we evaluated the effect of depressive
      symptomatology on memory scores across a 5-year period. Of 1,401 participants,
      210 had elevated depressive symptoms at baseline, as measured by a 12-item
      version of the Center for Epidemiological Studies-Depression Scale (CES-D).
      RESULTS: Participants with elevated depressive symptoms scored significantly
      lower at baseline and had faster decline in memory performance than those
      exhibiting fewer depressive symptoms. Memory score differences among depressive
      symptom categories did not differ between training conditions. DISCUSSION:
      Findings suggest that elevated depressive symptoms may predict declines in memory
      ability over time, but do not attenuate gains from training. Training provides a
      potential method of improving memory which is robust to effects of depression.

PMID- 23006428
TI  - Short-term versus long-term effects of depressive symptoms on mortality in
      patients on dialysis.
AB  - OBJECTIVE: Depressive symptoms seem to pose a risk factor for mortality among
      patients on dialysis. It is currently unknown whether the association is only
      short-lived and whether associations over time depend on specific causes of
      mortality. METHODS: In a prospective nationwide cohort study, 1528 patients with
      end-stage renal disease starting on dialysis completed the Mental Health
      Inventory. Patients were observed up to 5 years or until the end of follow-up in
      April 2011. Cox regression analyses were used to calculate associations between
      depressive symptoms and short-term (0-6 months), medium-term (6-24 months), or
      long-term (24-60 months) cardiovascular and noncardiovascular mortality. RESULTS:
      The adjusted hazard ratio (HR) was 1.43 (95% confidence interval [CI] = 1.08
      1.88) for cardiovascular mortality and 2.07 (95% CI = 1.62-2.64) for
      noncardiovascular mortality. Depressive symptoms posed a strong risk factor for
      noncardiovascular mortality at the short term (HR = 2.82, 95% CI = 1.58-5.05),
      medium term (HR = 2.08, 95% CI = 1.40-3.09), and long term (HR = 1.84, 95% CI =
      1.26-2.69), whereas the association between depressive symptoms and
      cardiovascular mortality was not observed during the first 6 months of follow-up
      (HR = 1.03, 95% CI = 0.49-2.15). CONCLUSIONS: Depressive symptoms at the start of
      dialysis therapy are associated with short-, medium-, and long-term mortality.
      The cause-specific mortality risk over time may help clinicians to understand
      multifactorial causes of the association between depressive symptoms and
      survival.

PMID- 23006429
TI  - Cognitive-perceptual factors in noncardiac chest pain and cardiac chest pain.
AB  - OBJECTIVE: Noncardiac chest pain (NCCP) is a common condition associated with
      considerable patient distress and substantial healthcare costs. Our aim was to
      investigate associations between illness perceptions, anxiety sensitivity,
      somatic amplification, and experience of chest pain, and to assess whether a
      multifactorial model including these factors can distinguish patients with NCCP
      from patients with cardiac chest pain (CCP). METHODS: A total of 240 patients
      with chest pain answered questionnaires concerning anxiety sensitivity (Anxiety
      Sensitivity Index-3), somatic amplification (Somatosensory Amplification Scale),
      illness perceptions (Illness Perception Questionnaire-Brief, health concerns, and
      heart disease conviction), and pain characteristics (intensity, disability, and
      frequency) before the evaluation of chest pain causation. They were classified as
      having NCCP or CCP by cardiac angiography. Partial correlation analyses and
      binary logistic regression analyses were performed. RESULTS: Seventy percent of
      patients with chest pain were classified as having NCCP. A range of cognitive
      perceptual factors were associated with the experience of chest pain. On
      multivariate analyses, the only psychological factor found to differentiate NCCP
      from CCP was elevated somatic amplification (relative risk = 1.06, 95% confidence
      interval = 1.00-1.13). CONCLUSIONS: The current DSM-5 proposal with regard to
      somatic symptom disorder recommends using psychological factors as diagnostic
      criteria for medically unexplained symptoms while placing less emphasis on the
      criterion of lack of somatic causation. In this study, an association between
      pain characteristics and cognitive-perceptual factors was found both for patients
      with NCCP and for patients with CCP. We found no evidence for a specific profile
      of psychological characteristics distinguishing patients with NCCP from patients
      with CCP, except for somatic amplification.

PMID- 23006430
TI  - Cerebral blood flow dynamics during pain processing in patients with fibromyalgia
      syndrome.
AB  - OBJECTIVES: Increased cerebral blood flow during processing of acute pain has
      repeatedly been observed in fibromyalgia syndrome. The study investigated the
      time dynamics of the pain-related hemodynamic response in fibromyalgia using
      transcranial Doppler sonography. METHODS: In 25 women with fibromyalgia and 25
      healthy participants, blood flow velocities in the anterior and middle cerebral
      arteries of both hemispheres were recorded, while heat stimuli of 45 degrees C
      were applied to their forearms. Thermal pain threshold and subjective pain
      experience during stimulation were assessed, and the participants completed the
      McGill Pain Inventory, Beck Depression Inventory, and State-Trait Anxiety
      Inventory. RESULTS: The early component of the blood flow response in both
      anterior cerebral arteries, that is, the steep flow increase during the initial
      stimulation period, was more pronounced in the patients than in the controls
      (mean [standard deviation] = 1.28% [1.85%] versus 0.24% [1.58%], p = .04). The
      patients showed lower pain threshold (p = .018), stronger sensory and affective
      pain experience (p < .001), and increased values on all questionnaire scales (all
      p values < .001). Although higher scores on each of the scales were associated
      with a stronger early blood flow response (r values ranging from 0.17 to 0.36),
      clinical pain severity proved to be the best predictor (beta = .33, p = .02).
      CONCLUSIONS: The increased blood flow response in the anterior cerebral arteries
      reflects hyperactivity of medial structures of the neuromatrix of nociception,
      structures involved in the processing of affective and cognitive aspects of pain.
      Aberrances in cerebral blood flow related to fibromyalgia and its clinical
      characteristics become particularly apparent in the enhancement of the initial
      component of the hemodynamic response.

PMID- 23006431
TI  - Burnout and risk of coronary heart disease: a prospective study of 8838
      employees.
AB  - OBJECTIVE: Burnout is a negative affective state consisting of emotional
      exhaustion, physical fatigue, and cognitive weariness symptoms. This study was
      designed to evaluate prospectively the association between burnout and coronary
      heart disease (CHD) incidence and to test the possibility that this association
      is nonlinear. METHODS: Participants were 8838 apparently healthy employed men and
      women, aged 19 to 67 years, who came for routine health examinations at the Tel
      Aviv Sourasky Medical Center. They were followed up for 3.4 years on average.
      Burnout was measured by the Shirom-Melamed Burnout Measure. CHD incidence was
      defined as a composite of acute myocardial infarction, diagnosed ischemic heart
      disease, and diagnosed angina pectoris. RESULTS: During follow-up, we identified
      93 new cases of CHD. Baseline levels of burnout were associated with an increased
      risk of CHD, after adjustment for various risk factors (hazard ratio = 1.41; 95%
      confidence interval = 1.08-1.85). In addition, we observed a significant
      threshold effect of burnout on CHD incidence. Participants who scored high on
      burnout (scores in the upper quintile of the Shirom-Melamed Burnout Measure
      scores distribution) had a higher risk (hazard ratio = 1.79; 95% confidence
      interval = 1.05-3.04) of developing CHD on follow-up compared with others.
      CONCLUSIONS: Burnout is an independent risk factor for future incidence of CHD.
      Individuals with high levels of burnout (upper quintile) have a significantly
      higher risk of developing CHD compared with those with low levels of burnout.

PMID- 23006432
TI  - First-principles study of bubble nucleation and growth behaviors in alpha U-Zr.
AB  - Bubble nucleation and growth is responsible for swelling in metallic fuels such
      as U-Zr. Computational modeling is useful for understanding and ultimately
      developing mitigation strategies for the swelling behavior of the fuel. However,
      the relevant fundamental parameters are not currently available. In our previous
      work, the formation energy and migration barrier of uranium vacancies and
      interstitials in alpha U have been obtained by first-principles calculations, and
      the calculated diffusion activation energy agrees reasonably well with the
      experimental results, within 0.1 eV (Huang and Wirth 2011 J. Phys.: Condens.
      Matter 23 205402). In this paper, the formation energy and migration barrier of
      Xe, Zr, Pu, in addition to the binding energy of small vacancy clusters, Xe
      vacancy clusters, and small interstitial clusters are investigated. These are
      among the essential data essential for the analysis and computational modeling of
      swelling in metallic nuclear fuel.

PMID- 23006433
TI  - Prediction of significant fibrosis and cirrhosis in hepatitis B e-antigen
      negative patients with chronic hepatitis B using routine parameters.
AB  - AIM: As liver biopsy has considerable limitations in the assessment of liver
      fibrosis, non-invasive models have achieved great progress in the past. However,
      many tests consist of variables that are not readily available, and there are few
      data about patients with hepatitis B e-antigen (HBeAg) negative chronic hepatitis
      B (CHB). The aim of this study was to develop a model using routine data to
      predict liver fibrosis in HBeAg negative CHB patients. METHODS: We randomly
      divided 349 patients who underwent liver biopsy into training (n = 200) and
      validation (n = 149) sets. Multivariable logistic regression and receiver
      operator curve (ROC) analyses were used to develop a model for predicting both
      significant fibrosis (stages 2-4) and cirrhosis (stage 4) in the training set.
      The model was validated in 149 patients in comparison to FIB-4, Forn's, S and
      aspartate aminotransferase-to-platelet ratio index indices using ROC. RESULTS:
      Multivariable logistic regression analysis showed that the parameters of the
      model for predicting both significant fibrosis and cirrhosis included sex, age,
      prothrombin time, platelet count, cholesterol and gamma-glutamyltransferase. In
      the training set, the areas under the ROC (AUC) for predicting significant
      fibrosis and cirrhosis were 0.856 and 0.956, respectively. In the validation
      group, the AUC for predicting significant fibrosis and cirrhosis were 0.889 and
      0.937, respectively. Using the best cut-off values, significant fibrosis and
      cirrhosis can be accurately predicted in 40.9% and 91.3% of patients,
      respectively. CONCLUSION: Our model can accurately predict both significant
      fibrosis and cirrhosis and may decrease the need of liver biopsy in a
      considerable proportion of patients with HBeAg negative CHB.

PMID- 23006434
TI  - Stereoselective and catalytic access to beta-enaminones: an entry to pyrimidines.
AB  - We describe herein a highly stereoselective access to Cbz-protected beta
      enaminones 2 based on the NaOH catalyzed rearrangement of propargylic
      hydroxylamines 1. The synthetic potential of these beta-enaminones is illustrated
      in an original synthesis of pyrimidines.

PMID- 23006435
TI  - Correlates associated with unipolar depressive disorders in a Latino population.
AB  - BACKGROUND: This study reports the comparison and associations of demographic,
      clinical and psychosocial correlates with three unipolar depressive disorders:
      dysthymia (DYS), major depression (MD) and double depression (DD), and examines
      to which extent these variables predict the disorders. SAMPLING AND METHOD:
      Previously collected data from 563 adults from a community in Puerto Rico were
      analyzed. One hundred and thirty individuals with DYS, 260 with MD and 173 with
      DD were compared by demographic variables, psychiatric and physical comorbidity,
      familial psychopathology, psychosocial stressors, functional impairment, self
      reliance, problem recognition and formal use of mental health services.
      Multinomial regression was used to assess the association of the predictor
      variables with each of the three disorders. RESULTS: Similarities outweighed the
      discrepancies between the disorders. The main differences observed were between
      MD and DD, while DYS shared common characteristics with both MD and DD. After
      other variables were controlled, anxiety, functional impairment and problem
      recognition most strongly predicted a DD diagnosis, while age predicted a DYS
      diagnosis. CONCLUSION: MD, DYS and DD are not completely different disorders, but
      they do differ in key aspects that might be relevant for nosology, research and
      practice. A dimensional system that incorporates specific categories of disorders
      would better reflect the different manifestations of unipolar depressive
      disorders.

PMID- 23006436
TI  - Going for the gusto: competing for the first time at age 65.
AB  - Older adults are often viewed by society more for what they cannot do than for
      what they are capable of achieving. This intrinsic case study examined the
      formation of a women's 65+ volleyball team at a university for the purpose of
      better understanding what it was like for older women to learn a new sport and
      what meaning participating in competitive sport had for those who had not
      previously been considered athletic. Qualitative methods explored each
      participant's experiences through a focus group, individual interviews,
      observational notes, and written reflections. Resulting team member themes
      included going for the gusto, belonging to a team, and support from the
      university. This program is a potential model to engage nonathletic older adults
      in sport, while forging a new and positive aging framework for aging athletes. 

PMID- 23006438
TI  - Emerging myxosporean parasites of Australian frogs take a ride with fresh fruit
      transport.
AB  - BACKGROUND: The spread of wildlife pathogens into new geographical ranges or
      populations is a conservation concern for endangered species. Cystodiscus
      australis and Cystodiscus axonis are two species of myxosporean parasites
      infecting Australian frogs and tadpoles that have been recently recognised as
      important disease agents impacting amphibian conservation. Yet despite their
      importance to wildlife health, the mechanism of emergence for these parasites is
      unknown. We hypothesise that these parasites are capable of being accidentally
      translocated with their amphibian hosts in fresh produce (agricultural,
      horticultural and industrial) shipments into naive environments and host
      populations. METHODS: We surveyed 33 Australian "Banana box" frogs from Sydney
      fruit markets during 2011 using faecal smears and multiplex species specific PCR
      on DNA isolated from frog faeces or using histopathology to demonstrate the
      presence of both C. australis and C. axonis. RESULTS: One of the "Banana box"
      frogs, the Dainty green tree frog (Litoria gracilenta) was positive for C.
      australis and C. axonis in its faeces and continuously shed the parasites for
      eight months. CONCLUSIONS: We present a possible mechanism for the emergence of
      Cystodiscus parasites and a non-invasive screening method to be used as a
      diagnostic test. In the future, vigilance and communication between wildlife
      managers/researchers and veterinarians will provide valuable information about
      these parasites, their host range and true distribution. This will aid risk
      management assessments for threatened populations within the range of Cystodiscus
      parasites and ultimately enhance conservation efforts.

PMID- 23006437
TI  - Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile
      women with endometriosis.
AB  - BACKGROUND: In order to obtain a lead of the pathophysiology of endometriosis,
      genome-wide expressional analyses of eutopic and ectopic endometrium have earlier
      been reported, however, the effects of stages of severity and phases of menstrual
      cycle on expressional profiles have not been examined. The effect of genetic
      heterogeneity and fertility history on transcriptional activity was also not
      considered. In the present study, a genome-wide expression analysis of
      autologous, paired eutopic and ectopic endometrial samples obtained from fertile
      women (n=18) suffering from moderate (stage 3; n=8) or severe (stage 4; n=10)
      ovarian endometriosis during proliferative (n=13) and secretory (n=5) phases of
      menstrual cycle was performed. METHODS: Individual pure RNA samples were
      subjected to Agilent's Whole Human Genome 44K microarray experiments. Microarray
      data were validated (P<0.01) by estimating transcript copy numbers by performing
      real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data
      obtained were subjected to differential expression (DE) and differential co
      expression (DC) analyses followed by networks and enrichment analysis, and gene
      set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA
      implementation of DC results was assessed by examining the relative expressions
      of twenty eight (28) selected genes in RNA samples obtained from fresh pool of
      eutopic and ectopic samples from confirmed ovarian endometriosis patients with
      stages 3 and 4 (n=4/each) during proliferative and secretory (n=4/each) phases.
      RESULTS: Higher clustering effect of pairing (cluster distance, cd=0.1) in
      samples from same individuals on expressional arrays among eutopic and ectopic
      samples was observed as compared to that of clinical stages of severity (cd=0.5)
      and phases of menstrual cycle (cd=0.6). Post hoc analysis revealed anomaly in the
      expressional profiles of several genes associated with immunological, neuracrine
      and endocrine functions and gynecological cancers however with no overt oncogenic
      potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC)
      major transcription factors appeared to be significant causative factors in the
      pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes
      representing potential marker for ovarian endometriosis in fertile women was
      discovered. CONCLUSIONS: Dysfunctional expression of immuno-neuro-endocrine
      behaviour in endometrium appeared critical to endometriosis. Although no overt
      oncogenic potential was evident, several genes associated with gynecological
      cancers were observed to be high in the expressional profiles in endometriotic
      tissue.

PMID- 23006440
TI  - Sequential interaction of phenytoin and phenobarbital with fluorouracil.
AB  - OBJECTIVE: We report a case of sequential interaction of phenytoin (PHT) and
      phenobarbital (PB) with fluorouracil (5-FU). CASE REPORT: A male patient aged 60
      under treatment with PHT and PB in which serum concentrations of PHT (32.8
      MUg/ml) and PB (26.7 MUg/ml) increased ~ 2-fold after the start of postoperative
      adjuvant therapy with calcium levofolinate (l-LV) and fluorouracil (5-FU). When
      the drug interactions of this case evaluated using the Drug Interaction
      Probability Scale, was assessed as "probable". DISCUSSION: In this case, 5-FU
      increased PHT, which in turn may have increased the PB concentration, suggesting
      that when fluoropyrimidine antitumor agents are administered to patients
      receiving PHT in combination with other drugs, some measures should be taken in
      consideration of secondary effects of antitumor agents on other drugs that may
      possibly interact with PHT, including frequent monitoring of blood drug
      concentration.

PMID- 23006439
TI  - Humoral immune response following seasonal influenza vaccine in islet transplant
      recipients.
AB  - Annual influenza vaccine is recommended for organ transplant recipients, but
      immunogenicity is known to be suboptimal. Islet transplant recipients receive
      immunosuppressive therapy, but there are no data on the immunogenicity of
      influenza vaccine in this population. In this prospective cohort study, adult
      islet transplant recipients at least 3 months posttransplant were enrolled. All
      patients received the 2010-2011 seasonal influenza vaccine. Serum was obtained
      pre- and postvaccination to determine humoral response to each of the three
      influenza strains included in the vaccine. Adverse effects of vaccine were also
      noted. A total of 61 islet transplant recipients were enrolled and completed the
      study protocol. The median time from last transplant was 1.9 years (range 0.26
      11.4 years), and most patients had undergone multiple prior islet transplant
      procedures (90.2%). Overall immunogenicity of the vaccine was poor.
      Seroconversion rates to H1N1, H3N2, and B antigens were 34.4%, 29.5%, and 9.8%,
      respectively. In the subset not seroprotected at baseline, a protective antibody
      titer postvaccination was achieved in 58.6%, 41.9%, and 34.5% of patients,
      respectively. Patients within the first year of transplant were significantly
      less likely to seroconvert to at least one antigen (23.5% vs. 54.5%; p = 0.029).
      Alemtuzumab recipients trended toward lower seroconversion rates (25% vs. 51%; p
      = 0.11). No vaccine-related safety concerns were identified. Seasonal influenza
      vaccine had suboptimal immunogenicity in islet transplant recipients especially
      those who were less than 1 year posttransplant or had received alemtuzumab
      induction. Novel strategies for protection in this group of patients need further
      study.

PMID- 23006441
TI  - Associations between prescribing nonsteroidal anti-inflammatory drugs and the
      potential prescription-related problems in a primary care setting.
AB  - OBJECTIVES: The objectives of this study were 1) to obtain information regarding
      the prescribing pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) in the
      primary care setting at a Malaysian university, 2) to determine the prevalence
      and types of potential NSAID prescription related problems (PRPs), and 3) to
      identify patient characteristics associated with exposure to these potential
      PRPs. METHODS: We retrospectively collected data from 1 academic year using the
      electronic medical records of patients in the University Sains Malaysia (USM)
      primary care system. The defined daily dose (DDD) methodology and the anatomical
      therapeutic chemical (ATC) drug classification system were used in the analysis
      and comparison of the data. Statements representing potential NSAID PRPs were
      developed from authoritative drug information sources. Then, algorithms were
      developed to screen the databases for these potential PRPs. Descriptive and
      comparative statistics were used to characterize DRPs. RESULTS: During the study
      period, 12,470 NSAID prescriptions were prescribed for 6,509 patients (mean +/-
      SD = 1.92 +/- 1.83). This represented a prevalence of 35,944 per 100,000
      patients, or 36%. Based on their DDDs, mefenamic acid and diclofenac were the
      most prescribed NSAIDs. 573 potential NSAID-related PRPs were observed in a
      cohort of 432 patients, representing a prevalence of 6,640 per 100,000 NSAIDs
      users, or 6.6% of all NSAID users. Multivariate logistic regression analysis
      revealed that patients with a Malay ethnic background (p < 0.001), members of the
      staff (p < 0.001), having 4 or more prescribers (p < 0.001) or having 2 - 3
      prescribers (p = 0.02), and representing 4 or more long-term therapeutic groups
      (LTTGs) (p < 0.001) or 2 - 3 LTTGs (p < 0.001) were significantly associated with
      an increased chance of exposure to potential NSAID related PRPs. CONCLUSIONS:
      This is the first study in Malaysia that presents data on the prescribing pattern
      of NSAIDs and the characteristics of potential NSAID-related PRPs. The prevalence
      of potential NSAID-related PRPs is frequent in the primary care setting. Exposure
      to these PRPs is associated with specific sociodemographic and health status
      factors. These results should help to raise the awareness of clinicians and
      patients about serious NSAID PRPs.

PMID- 23006442
TI  - Assessment of the influence of severe renal impairment on the pharmacokinetics of
      mirodenafil in Korean male volunteers.
AB  - OBJECTIVE: To evaluate and compare the pharmacokinetics and tolerability of a
      single oral dose of mirodenafil in volunteer patients with severe renal
      impairment and healthy volunteers. METHODS AND MATERIALS: This open-label, single
      dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy
      volunteers and 6 volunteer patients with severe renal impairment). Each volunteer
      was orally administered 50 mg mirodenafil and serial blood samples were obtained
      after drug administration to determine the plasma concentration of mirodenafil
      using LC-MS/MS. The measured individual plasma concentrations were used to
      calculate the pharmacokinetic parameters using noncompartmental methods.
      Tolerability was also assessed using measurements of vital signs, clinical
      chemistry tests, and interviews. RESULTS: All of the volunteers completed the
      study with no serious adverse events (AEs). A total of 4 AEs were reported, but
      all were of mild or moderate intensity and not considered to be related to the
      study drug. The geometric mean (95% CI) of the terminal half-life (t1/2beta) and
      the apparent clearance (CL/F) values of mirodenafil were 2.2 (1.4 - 3.4) h and
      127.2 (95.1 - 170.2) l/h in the volunteer patients, and 3.0 (2.1 - 4.4) h and
      136.1 (74.4 - 249.2) l/h in the healthy volunteers, respectively. The geometric
      mean of the AUC0-t of the volunteer patients was 8% higher and the geometric mean
      for clearance was 7% lower compared with the healthy volunteers. However, the
      geometric mean of the Cmax of the volunteer patients was 38% higher than that of
      the healthy volunteers. CONCLUSIONS: A single oral 50-mg dose of mirodenafil was
      well tolerated. Exposure (AUC0-t) to mirodenafil was similar in both healthy
      volunteers and volunteer patients with severe renal impairment and healthy
      volunteers.

PMID- 23006443
TI  - Bioequivalence and pharmacokinetics of two 10-mg bisoprolol formulations as film
      coated tablets in healthy white volunteers: a randomized, crossover, open-label,
      2-period, single-dose, fasting study.
AB  - OBJECTIVE: The aim of the study was to investigate the bioavailability of a
      generic formulation of 10-mg bisoprolol film coated tablets (test) as compared to
      that of a branded formulation (reference) at the same strength to determine
      bioequivalence and to apply for regulatory approval. The secondary objective of
      the study was to evaluate tolerability of both formulations. METHODS: A
      randomized, crossover, open-label, 2-period, single-dose, comparative study was
      conducted in healthy white volunteers in fasting conditions. A single oral dose
      administration of the test or reference formulation was followed by a 14-day wash
      out period. Blood samples were collected up to 60 hours after dosing. The
      bisoprolol concentrations in plasma samples were determined using a validated LC
      MS/MS method. The formulations were considered bioequivalent if 90% CI of
      geometric mean ratios (test/reference) for AUC0-t, AUC0-infinity and Cmax were
      within the range 80.00 - 25.00%. Adverse events were monitored throughout the
      study based on the clinical parameters and volunteer reports. RESULTS: Healthy
      male and female subjects participating in the study had a median (range) age of
      23 (20 - 43), weight of 68 kg (52 - 84), height of 172 cm (157 - 184), and BMI of
      23.1 kg/m2 (19.3 - 24.9). The 26 consented volunteers have been included and 24
      of them completed the clinical part of the study. The geometric mean
      test/referenceratios (90% CI) for AUC0-t, AUC0-infinity and Cmax were 104.12%
      (100.52 - 107.85%), 104.05% (100.49 - 107.75%) and 107.91% (103.04 - 112.99%),
      respectively. All 90% CI were embraced by the 80.00 - 25.00% acceptance interval.
      No serious adverse events were reported. A total number of 6 non-serious,
      moderate adverse events were registered, including headache and vomiting in one
      subject. CONCLUSIONS: The results of the single-dose study in healthy white
      volunteers indicated that the film-coated tablets of Bisocard(r) 10 mg
      manufactured by ICN Polfa Rzeszow S.A. (test formulation) are bioequivalent to
      those of Concor 10(r) manufactured by Merck KGaA (reference formulation). Both
      formulations were well tolerated.

PMID- 23006444
TI  - Platelet activation markers after conversion from azathioprine to sirolimus based
      immunosuppression in renal transplant recipients.
AB  - OBJECTIVE: Under immunosupression with sirolimus (rapamycin) procoagulant effects
      and platelet activation have been controversially discussed. METHODS: We
      evaluated patients of a prospectly designed substudy as part of a randomized
      trial investigating the effect of a switch from non-mTOR-based immunosuppression
      to sirolimus in renal transplant recipients. Our substudy consisted of 7 patients
      who switched therapy from azathioprine to sirolimus (conversion group) and 8
      patients who remained on azathioprine (controls) before (V1) and after (V2) 3
      months of treatment. In all patients we assessed flowcytometric markers of
      platelet activation (PAC-1), platelet degranulation (CD62P), formation of
      platelet leukocyte-aggregates (PLA), monocyte activation (CD11b), endogenous
      thrombin potential (ETP) and platelet aggregation. RESULTS: Both groups were
      similar in terms of baseline demographics and had stable transplant function for
      at least 6 months. CD62P increased significantly in the control group (p < 0.03).
      PLA were significantly reduced in the sirolimus conversion group at V2 (p <
      0.02), whereas no effect was seen in the controls. Expression of PAC-1, CD11b,
      ETP-peak, ETP-time to peak, ETP-AUC and platelet aggregation showed no
      significant changes in both groups compared to V2. CONCLUSION: From clinical
      data, performing in depth platelet function testing, we found no evidence for
      increased platelet activation parameters in RTR who switched therapy from
      azathioprine to sirolimus.

PMID- 23006445
TI  - A survey of Mycoplasma agalactiae in dairy sheep farms in Spain.
AB  - BACKGROUND: Contagious Agalactia (CA) is one of the major animal health problems
      in small ruminants because of its economic significance. Currently, four
      Mycoplasma spp. have been associated with this syndrome: M. agalactiae, M.
      mycoides subsp. capri, M. capricolum subsp. capricolum and M. putrefaciens. Their
      presence has been evaluated in several studies conducted in CA-endemic countries.
      However, previous Spanish studies have been focused on caprine CA, and there is a
      knowledge gap regarding which Mycoplasma species are present in sheep flocks from
      Spain, which has the second highest number of sheep amongst the 27 European Union
      member states. Consequently, we investigated the presence and geographic
      distribution of the four CA-causing mycoplasmas in Spanish dairy sheep farms.
      This is the first time such an investigation has been performed. RESULTS: Three
      hundred thirty nine out of 922 sheep flocks were positive for M. agalactiae by
      real time PCR (36.8%) and 85 by microbiological identification (9.2%).
      Interestingly, all 597 milk samples assessed for the presence of M. mycoides
      subsp. capri, M. capricolum subsp. capricolum and M. putrefaciens tested
      negative. To evaluate the intermittent excretion of the pathogen in milk, we
      sampled 391 additional farms from 2 to 5 times, resulting that in 26.3% of the
      cases a previously positive farm tested negative in a later sampling.
      CONCLUSIONS: M. agalactiae was the only Mycoplasma species detected in the study
      area showing a high frequency of presence and wide distribution. Therefore, the
      establishment of a permanent surveillance network is advantageous, as well as the
      implementation of control and prevention measures to hinder the dissemination of
      M. agalactiae and to prevent the entrance of other Mycoplasma species.

PMID- 23006358
TI  - Search for new physics with same-sign isolated dilepton events with jets and
      missing transverse energy.
AB  - A search for new physics is performed in events with two same-sign isolated
      leptons, hadronic jets, and missing transverse energy in the final state. The
      analysis is based on a data sample corresponding to an integrated luminosity of
      4.98 fb(-1) produced in pp collisions at a center-of-mass energy of 7 TeV
      collected by the CMS experiment at the LHC. This constitutes a factor of 140
      increase in integrated luminosity over previously published results. The observed
      yields agree with the standard model predictions and thus no evidence for new
      physics is found. The observations are used to set upper limits on possible new
      physics contributions and to constrain supersymmetric models. To facilitate the
      interpretation of the data in a broader range of new physics scenarios,
      information on the event selection, detector response, and efficiencies is
      provided.

PMID- 23006447
TI  - A randomized, phase 2 study comparing pemetrexed plus best supportive care versus
      best supportive care as maintenance therapy after first-line treatment with
      pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer.
AB  - BACKGROUND: Maintenance therapy for non-small cell lung cancer (NSCLC) aims to
      extend disease control after first-line chemotherapy with active and well
      tolerated agents. The utility of continuation maintenance therapy requires
      further research. METHODS: This multicenter, randomized, phase 2 study compared
      continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and
      best supportive care (BSC) versus BSC alone in patients with advanced, non
      squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy
      with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was
      progression-free survival (PFS) from randomization, was analyzed using a Cox
      model, stratified for the tumor response at the end of induction therapy, at a
      one-sided alpha of 0.2. Secondary endpoints: response and disease control rates,
      overall survival (OS), one year survival rates, and treatment-emergent adverse
      events (TEAEs). RESULTS: A total of 106 patients commenced induction therapy, of
      whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n
      = 27). Although the median PFS time for maintenance phase for both arms was 3.2
      months, the one-sided p-value for the PFS HR comparison was less than the
      prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]:
      0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently
      long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS
      results were observed for the overall study period (induction plus maintenance)
      and when the PFS analysis was adjusted for sex, baseline disease stage, and the
      ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2
      months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI:
      6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for
      both arms for the maintenance phase and the overall study period. Both the
      induction and continuation maintenance therapies were generally well-tolerated,
      and similar proportion of patients in each arm experienced at least 1 grade 3/4
      TEAE (pemetrexed/BSC, 17.9%; BSC, 18.5%). CONCLUSIONS: Continuation pemetrexed
      maintenance therapy resulted in promising PFS with an acceptable safety profile
      in a Middle Eastern population with advanced non-squamous NSCLC and is worthy of
      further investigation. TRIAL REGISTRATION: NCT00606021.

PMID- 23006446
TI  - Identification and characterization of circadian clock genes in a native tobacco,
      Nicotiana attenuata.
AB  - BACKGROUND: A plant's endogenous clock (circadian clock) entrains physiological
      processes to light/dark and temperature cycles. Forward and reverse genetic
      approaches in Arabidopsis have revealed the mechanisms of the circadian clock and
      its components in the genome. Similar approaches have been used to characterize
      conserved clock elements in several plant species. A wild tobacco, Nicotiana
      attenuata has been studied extensively to understand responses to biotic or
      abiotic stress in the glasshouse and also in their native habitat. During two
      decades of field experiment, we observed several diurnal rhythmic traits of N.
      attenuata in nature. To expand our knowledge of circadian clock function into the
      entrainment of traits important for ecological processes, we here report three
      core clock components in N. attenuata. RESULTS: Protein similarity and transcript
      accumulation allowed us to isolate orthologous genes of the core circadian clock
      components, LATE ELONGATED HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION 1/PSEUDO
      RESPONSE REGULATOR 1 (TOC1/PRR1), and ZEITLUPE (ZTL). Transcript accumulation of
      NaLHY peaked at dawn and NaTOC1 peaked at dusk in plants grown under long day
      conditions. Ectopic expression of NaLHY and NaZTL in Arabidopsis resulted in
      elongated hypocotyl and late-flowering phenotypes. Protein interactions between
      NaTOC1 and NaZTL were confirmed by yeast two-hybrid assays. Finally, when NaTOC1
      was silenced in N. attenuata, late-flowering phenotypes under long day conditions
      were clearly observed. CONCLUSIONS: We identified three core circadian clock
      genes in N. attenuata and demonstrated the functional and biochemical
      conservation of NaLHY, NaTOC1, and NaZTL.

PMID- 23006448
TI  - DNA barcoding reveals taxonomic conflicts in the Herichthys bartoni species group
      (Pisces: Cichlidae).
AB  - Fishes of the genus Herichthys are the only representatives of the family
      Cichlidae to have colonized the Neartic region. In this study, we used DNA
      barcode of 64 individuals of the Herichthys bartoni species group to test the
      monophyly of the species and the efficiency of this tool to discriminate among
      species. The Bayesian phylogenetic tree and the neighbour joining (NJ) tree
      obtained from the Kimura two-parameter model (K2P) give similar topologies. DNA
      barcoding resolution was very poor (25%). Additionally, the low levels of genetic
      divergence among taxa preclude the use of threshold values as has been suggested
      in earlier studies.

PMID- 23006450
TI  - Statement of concern about a commercial assay used to measure soluble hemojuvelin
      in humans.

PMID- 23006449
TI  - Kinesin expression in the central nervous system of humans and transgenic
      hSOD1G93A mice with amyotrophic lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis is a fatal motor neuron degenerative
      disease. Most cases are sporadic (SALS), and approximately 10% are familial
      (FALS) among which over 20% are linked to the SOD1 mutation. Both SALS and FALS
      have been associated with retrograde axonal transport defects. Kinesins (KIFs)
      are motor proteins involved mainly in anterograde transport; however, some also
      participate in retrograde transport. OBJECTIVE: The purpose of the study was to
      investigate and compare the expression of kinesins involved in anterograde
      (KIF5A, 5C) and retrograde (KIFC3/C2) axonal transport in SALS in humans and FALS
      in mice with the hSOD1G93A mutation. METHODS: The studies were conducted on
      various parts of the CNS from autopsy specimens of SALS patients, and transgenic
      mice at presymptomatic and symptomatic stages using real-time quantitative PCR
      and reverse-transcription PCR. RESULTS: All KIF expression in the motor cortex of
      individual SALS subjects was higher than in the adjacent sensory cortex, in
      contrast to the expression in control brains. It was also significantly higher in
      the frontal cortex of symptomatic but not presymptomatic mice compared to wild
      type controls. However, the mean KIF expression in the SALS motor and sensory
      cortexes was lower than in control cortexes. To a lesser extent the decrease in
      KIF mean expression also occurred in human but not in mouse ALS spinal cords and
      in both human and mouse cerebella. CONCLUSION: Disturbances in kinesin expression
      in the CNS may dysregulate both anterograde and retrograde axonal transports
      leading to motor neuron degeneration.

PMID- 23006451
TI  - Incremental value of perfusion over wall-motion abnormalities with the use of
      dobutamine-atropine stress myocardial contrast echocardiography and magnetic
      resonance imaging for detecting coronary artery disease.
AB  - BACKGROUND: Recently, multimodality imaging has been demonstrated to improve the
      sensitivity of dobutamine stress for the diagnosis of coronary artery disease
      (CAD). OBJECTIVE: We sought to determine the additional value of myocardial
      perfusion (MP) over wall-motion (WM) analysis for detecting CAD, using real time
      myocardial contrast echocardiography (RTMCE) and cardiovascular magnetic
      resonance (CMR), in the same group of patients. METHODS: We studied 42 patients
      who underwent RTMCE and CMR during high-dose dobutamine stress with early
      injection of atropine. RESULTS: No difference was observed in the diagnostic
      accuracy of RTMCE and CMR for detecting angiographically significant CAD when
      considering WM analysis alone (73% [95% CI, 65-81] and 78% [95% CI, 70-84],
      respectively; P = NS) or combined analysis of WM and MP (80% [95% CI, 73-97] and
      83% [95% CI, 77-90], respectively; P = NS). Combined analysis of WM and MP had
      higher sensitivity than the analysis of WM alone by RTMCE (88% [95% CI, 75-100]
      vs. 72% [95% CI, 54-90]) and by CMR (92% [95% CI, 81-100] vs. 80% [95% CI, 64
      96]) with no differences in specificity. The association of abnormal WM and MP
      abnormalities during high-dose dobutamine-atropine stress had additional value
      for detecting CAD over the analysis of WM alone, both by RTMCE (chi(2) = 16.16
      24.13; P = 0.005) and CMR (chi(2) = 12.73-27.41; P = 0.001). CONCLUSION: RTMCE
      and CMR using the same dobutamine-atropine stress protocol had comparable
      diagnostic accuracies for the detection of angiographically significant CAD. MP
      imaging had additional value over WM analysis for the diagnosis of CAD, both at
      RTMCE and CMR.

PMID- 23006452
TI  - Relative validation of Block Kids Food Screener for dietary assessment in
      children and adolescents.
AB  - Food frequency questionnaires (FFQs) are less time consuming and inexpensive
      instruments for collecting dietary intake when compared with 24-h dietary recalls
      or double-labelled water; however, the validation of FFQ is important as
      incorrect information may lead to biased conclusions about associations.
      Therefore, the relative validity of the Block Kids Food Screener (BKFS) developed
      for use with children was examined in a convenience sample of 99 youth recruited
      from the Portland, OR metropolitan area. Three 24-h dietary recalls served as the
      reference. The relative validity was analysed after natural log transformation of
      all variables except glycaemic index prior to correlation analysis. Daily cup
      equivalent totals from the BKFS and 'servings' from 24-h recalls were used to
      compute average daily intake of fruits, vegetables, potatoes, whole grains,
      legumes, meat/fish/poultry and dairy. Protein grams (g), total kcalories,
      glycaemic index (glucose reference), glycaemic load (glucose reference), total
      saturated fat (g) and added sugar (g) were also calculated by each instrument.
      The correlation between data obtained from the two instruments was corrected for
      the within-subject variation in food intake reported by the 24-h recalls using
      standard nutritional assessment methodology. The de-attenuated correlations in
      nutritional intake between the two dietary assessment instruments ranged from
      0.526 for vegetables, to 0.878 for potatoes. The 24-h recall estimated higher
      levels of saturated fat and added sugar consumption, higher glycaemic loads and
      glycaemic indices; the de-attenuatted correlations of these measures ranged from
      0.478 to 0.768. Assessment of Bland-Altman plots indicated no systematic
      difference between the two instruments for vegetable, dairy and meat/fish/poultry
      fat consumption. BKFS is a useful dietary assessment instrument for the nutrients
      and food groups it was designed to assess in children age 10-17 years. 

PMID- 23006453
TI  - Therapy students' recommendations of physical activity for managing persistent
      low back pain in older adults.
AB  - Negative views of older adults can lead to suboptimal care. For older adults with
      persistent low back pain (LBP), promotion of physical activity by health care
      professionals is important. Health care professionals' views of older adults are
      influenced by their training. This study aimed to compare recommendations for
      physical activity for managing persistent LBP offered by students in
      physiotherapy and occupational therapy to an older person vs. a younger person.
      In a cross-sectional online survey, participants (N = 77) randomly received a
      vignette of either a 40-yr-old or 70-yr-old patient with persistent LBP. Other
      than age, the vignettes were identical. There was no difference between the
      younger and older vignettes in the likelihood of participants making overall
      appropriate physical activity recommendations--63% vs. 59%, OR (95% CI) = 1.19
      (0.48-2.99), p = .71--although there was a trend toward age bias on
      recommendations specific to daily activity. Postqualification education may be
      where ageist views need to be addressed.

PMID- 23006454
TI  - Validation of FFQ-based assessment of dietary lignans compared with serum
      enterolactone in Swedish women.
AB  - The validity of using FFQ to assess dietary lignans is uncertain. We aimed to
      validate the use of FFQ for the assessment of dietary intake of lignans compared
      to the serum biomarker enterolactone, the main product of dietary lignans'
      metabolism in human subjects. A random sample of women, aged 55-75 years, from
      the Swedish Mammography Cohort was selected. Information from two FFQ, the FFQ-87
      (sixty-seven food items) and the FFQ-97 (ninety-three food items), and blood
      samples were collected. Dietary intake of lignans (secoisolariciresinol,
      matairesinol, lariciresinol, pinoresinol, medioresinol and syringaresinol) was
      assessed by the FFQ. Serum concentrations of enterolactone were analysed by time
      resolved fluoroimmunoassay. The correlation coefficient between energy-adjusted
      lignan intake and serum enterolactone was estimated in crude and multivariable
      adjusted models, taking into account the factors potentially influencing the
      serum enterolactone. Among the 135 participants aged 55-75 years, with a mean BMI
      of 26.7 kg/m2, the average energy-adjusted intake of total lignans was 1616 (sd
      424) and 1516 (sd 409) MUg/d according to the FFQ-87 (forty-five food items
      containing lignans) and the FFQ-97 (sixty-five food items containing lignans),
      respectively. The mean concentration of serum enterolactone was 23.2 (sd 15.4)
      nmol/l. The adjusted Pearson's correlation between dietary intake of lignans
      assessed by the FFQ-97 and serum enterolactone was statistically significant (r
      0.22, P= 0.01). No significant correlation was observed for the FFQ-87 (r 0.09,
      P= 0.30). The present study indicates that the FFQ-97 might be better than the
      FFQ-87 for assessing dietary intake of lignans, although the correlation was low.

PMID- 23006455
TI  - SASLT practice guidelines for the management of hepatitis C virus infection:
      summary of recommendations.

PMID- 23006456
TI  - Prediction of minimal hepatic encephalopathy.

PMID- 23006457
TI  - Hepatic encephalopathy.
AB  - Chronic liver disease and cirrhosis affect hundreds of millions of patients all
      over the world. The majority of patients with cirrhosis will eventually develop
      complications related to portal hypertension. One of these recurrent and
      difficult to treat complications is hepatic encephalopathy. Studies have
      indicated that overt hepatic encephalopathy affects 30 to 45% of patients with
      cirrhosis and a higher percentage may be affected by minimal degree of
      encephalopathy. All of these factors add to the impact of hepatic encephalopathy
      on the healthcare system and presents a major challenge to the
      gastroenterologist, hospitalist and primary care physician.

PMID- 23006458
TI  - Systematic review of diet in the pathogenesis of acute pancreatitis: a tale of
      too much or too little?
AB  - BACKGROUND/AIM: The role of diet as the cause of acute pancreatitis (AP) has been
      suggested. The aim of the current review was to determine if there exists
      sufficient evidence linking nutrition, or the lack of it, to the pathogenesis of
      AP. PATIENTS AND METHODS: A systematic search of the scientific literature was
      carried out using Embase, PubMed, MEDLINE, and the Cochrane Central Register of
      Controlled Trials for the years 1965 - 2011 to obtain access to studies involving
      dietary factors and the pathogenesis of AP. RESULTS: A total of 17 studies were
      identified describing diet and AP. These included 12 human and 5 animal studies.
      8 reports were found to link malnutrition and/or refeeding to the pathogenesis of
      AP. Two studies found an increased consumption of fats and proteins in patients
      with alcohol-related AP while 1 study noted a lesser intake of carbohydrate in
      patients. However, none of these differences attained statistical significance. A
      recent prospective case-control study found a significantly higher risk for AP
      amongst patients eating par-boiled rice and fresh water fish. CONCLUSIONS:
      Evidence from literature does not appear to support the role of diet as a single
      bolus meal as a cause for AP. Prolonged consumption of diets rich in proteins and
      fats may work synergistically with gallstones / alcohol to trigger an attack of
      AP indicating a possible role of diet as a cofactor in the development of AP
      possibly by lowering the threshold needed by these other agents to lead to the
      attack of AP.

PMID- 23006459
TI  - Minimal hepatic encephalopathy in patients with cirrhosis by measuring liver
      stiffness and hepatic venous pressure gradient.
AB  - BACKGROUND/AIM: Transient elastography (TE) of liver and hepatic venous pressure
      gradient (HVPG) allows accurate prediction of cirrhosis and its complications in
      patients with chronic liver disease. There is no study on prediction of minimal
      hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis.
      PATIENTS AND METHODS: Consecutive cirrhotic patients who never had an episode of
      hepatic encephalopathy (HE) were enrolled. All patients were assessed by
      psychometry (number connection test (NCT-A and B), digit symbol test (DST),
      serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test
      (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more
      abnormal psychometry tests (+/- 2 SD controls). RESULTS: 150 patients with
      cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 +/- 11.4
      years, M:F:75:16, Child's A:B:C 18:54:19) met the inclusion criteria. Fifty three
      (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C
      (14/19, 74%)). There was no significant difference between alanine
      aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin
      level in patients with MHE versus non MHE. Patients with MHE had significantly
      lower CFF than non MHE patients (38.4 +/- 3.0 vs. 40.2 +/- 2.2 Hz, P = 0.002). TE
      and HVPG in patients with MHE did not significantly differ from patients with no
      MHE (30.9 +/- 17.2 vs. 29.8 +/- 18.2 KPas, P = 0.78; and 13.6 +/- 2.7 vs. 13.6 +/
      3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with
      Child's score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001)
      while no correlation with psychometric tests, CFF and MHE. CONCLUSION: TE by
      FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with
      cirrhosis.

PMID- 23006460
TI  - Analysis of colonic mucosa mast cell count in patients with chronic diarrhea.
AB  - BACKGROUND/AIM: Chronic diarrhea is defined as a decrease in fecal consistency
      lasting for four or more weeks. Prevalence of this complication in the general
      population is 5%. Mast cells that play an important role in the regulation of
      gastrointestinal visceral sensitivity and vascular permeability may be involved
      in functional chronic diarrhea. In this study we tried to evaluate mast cells
      density in colonic mucosa of patients with chronic diarrhea. PATIENTS AND
      METHODS: 50 patients with chronic diarrhea and 50 persons as control group were
      investigated. All specimens were immunohistochemically stained for mast cell
      tryptase (MCT) with monoclonal mouse anti-human MCT as well as toluidine blue.
      Mean number of mucosal mast cells were counted in 10 high power microscopic
      fields of patients and control groups. RESULTS: In patients group (age range, 15
      78 years; 26 females), the number of mast cells per high power field in the
      immunohistochemistry staining was 21.3 +/- 4.8 compared to 14.2 +/- 3.4 in the
      control group (age range, 18-78 years; 24 females) [P < 0.001]. Also number of
      mast cells in toluidine blue staining was 10.3 +/- 3.6 per high power field in
      cases and 7.1 +/- 2.4 in the control group (P < 0.001). CONCLUSION: Elevated
      number of colonic mast cells exist in patients with chronic diarrhea. Further
      research should be considered on application of these findings for new
      therapeutic opportunities.

PMID- 23006461
TI  - Serum TGF-beta, Serum MMP-1, and HOMA-IR as non-invasive predictors of fibrosis
      in Egyptian patients with NAFLD.
AB  - BACKGROUND/AIM: Non-alcoholic fatty liver disease (NAFLD) is an increasingly
      prevalent cause of chronic liver disease worldwide. A number of these patients
      progress to nonalcoholic steatohepatitis (NASH) which carries significant
      morbidity and mortality. The aim of this study is to evaluate the diagnostic
      value of serum levels of transforming growth factor beta-1 (TGF-beta1) matrix
      metalloproteinase-1 (MMP-1), and insulin resistance as predictors of fibrosis in
      Egyptian NAFLD patients. PATIENTS AND METHODS: Fifty patients with NAFLD and
      different stages of fibrosis were studied. Serum levels of TGF-beta1, MMP-1, and
      fasting serum insulin were measured; calculation of the homeostasis model
      assessment for insulin resistance (HOMA-IR) was done. RESULTS: TGF-beta1 gives a
      sensitivity of 100% and specificity of 94.4% for stage 1 fibrosis, 100% and
      93.9%, respectively, for stage 2 fibrosis, and 97.7% and 100%, respectively, for
      stage 3 fibrosis. MMP-1 showed sensitivity and specificity of 88% and 81.8%,
      respectively, for stage 2 fibrosis, 90.9% and 55.56%, respectively, for stage 3
      fibrosis, but it is of no diagnostic value in stage 1 fibrosis. CONCLUSION: Serum
      TGF-beta1, MMP-1, and insulin resistance (HOMA-IR) proved to be potentially
      useful noninvasive markers in predicting fibrosis in NASH patients.

PMID- 23006462
TI  - Presentation, diagnosis and outcome of predominantly hepatic Wilson's disease in
      adult Saudi patients: a single centre experience.
AB  - BACKGROUND/AIM: To evaluate the clinical manifestations, diagnostic features,
      disease course and response to treatment among Saudi adults with predominantly
      hepatic Wilson's disease. A retrospective cohort study of 40 adult patients
      diagnosed with predominantly hepatic Wilson's disease between 1994 and 2008 at
      King Abdulaziz Medical City, Riyadh was carried out. PATIENTS AND METHODS: The
      diagnosis was based on varying combinations of clinical and laboratory evidence
      of liver disease, presence of Kayser Fleisher rings, low serum ceruloplasmin
      levels, elevated 24 hour urinary copper excretion and histopathological findings
      on liver biopsy. RESULTS: The most frequent clinical presentation was
      decompensated chronic liver disease in 19 (47.5%), followed by chronic hepatitis
      in 15 (37.5%) and fulminant hepatic failure (FHF) in 5 (12.5%) patients. Eight
      (20%) patients with end-stage liver disease had liver transplantation, while 24
      (60%) patients followed up on medical treatment for a variable period of 1-12
      years showed clinical and laboratory improvement. One patient was lost early in
      follow up. Eight (20%) patients died during the study period, 5 with FHF, and 2
      with advanced hepatic and neurological disease and one seven years after liver
      transplantation. Mortality rate was 100% in FHF without liver transplantation.
      CONCLUSION: A predominantly hepatic Wilson's disease has varied clinical
      presentations with decompensated chronic liver disease being the most common
      among adult patients. Majority of the patients show stabilization of the disease
      on medical treatment. FHF in Wilson's disease has a grave prognosis without liver
      transplantation, the later remains a definitive treatment option for
      decompensated cirrhotics and patients with FHF.

PMID- 23006463
TI  - Isolated cortisol deficiency: a rare cause of neonatal cholestasis.
AB  - For decades, congenital panhypopituitarism has been recognized to cause infantile
      cholestasis. However, the identity of the hormone whose deficiency causes such
      derangement of the liver is not clear. Here, we report four cases of isolated
      severe cortisol deficiency presenting with neonatal cholestasis and hypoglycemia,
      of whom two had familial primary glucocorticoid deficiency and the other two had
      isolated adrenocorticotropin deficiency. The resolution of cholestasis by
      hydrocortisone replacement therapy suggests a causal relationship between
      cortisol deficiency and the development of neonatal cholestasis. In conclusion,
      the presentation of a young infant with cholestasis and hypoglycemia should alert
      pediatricians to the possibility of cortisol deficiency and prompt investigation
      of adrenal function should be undertaken.

PMID- 23006464
TI  - Ruptured ileocolic artery aneurysm: an unusual cause of hemoperitoneum.
AB  - Ruptured aneurysm of a branch of ileocolic artery is a rare finding and is an
      unusual cause of haemoperitoneum. Rapid diagnosis, and surgical or endovascular
      intervention are necessary to avoid devastating consequences and high mortality
      rates following an emergency operation after rupture. Resection is a good choice
      for surgical intervention for some aneurysms that are not suitable for
      endovascular repair. This report describes the case of a middle-aged man with a
      ruptured superior mesenteric artery branch aneurysm and his subsequent surgical
      management.

PMID- 23006465
TI  - Umbilical nodule in cholangiocarcinoma. Sister Mary Joseph Nodule.

PMID- 23006467
TI  - Electronic properties of FeSe(1-x)Te(x) probed by x-ray emission and absorption
      spectroscopy.
AB  - The electronic structure of FeSe(1-x)Te(x) chalcogenide  superconductors has been
      studied by x-ray emission (XES) and x-ray absorption (XAS) as a function of Te
      substitution. The Fe Kbeta XES spectra reveal a relatively low spin state for Fe
      in FeSe(1-x)Te(x) superconductors, persisting in the whole range of Te
      substitution. The Fe K-edge high-resolution XAS shows systematic spectral changes
      due to the evolving hybridization between the Fe 3d (4p) and chalcogen p (d)
      orbitals. The resonant inelastic x-ray scattering (RIXS) spectra hardly show any
      feature except the one due to charge transfer from occupied to unoccupied bands,
      that changes substantially from FeSe to FeTe. The results provide important
      information on the electronic states and their evolution in the FeSe(1-x)Te(x)
      chalcogenides.

PMID- 23006466
TI  - Cost-effectiveness of counseling and pedometer use to increase physical activity
      in the Netherlands: a modeling study.
AB  - BACKGROUND: Counseling in combination with pedometer use has proven to be
      effective in increasing physical activity and improving health outcomes. We
      investigated the cost-effectiveness of this intervention targeted at one million
      insufficiently active adults who visit their general practitioner in the
      Netherlands. METHODS: We used the RIVM chronic disease model to estimate the long
      term effects of increased physical activity on the future health care costs and
      quality adjusted life years (QALY) gained, from a health care perspective.
      RESULTS: The intervention resulted in almost 6000 people shifting to more
      favorable physical-activity levels, and in 5100 life years and 6100 QALYs gained,
      at an additional total cost of EUR 67.6 million. The incremental cost
      effectiveness ratio (ICER) was EUR 13,200 per life year gained and EUR 11,100 per
      QALY gained. The intervention has a probability of 0.66 to be cost-effective if a
      QALY gained is valued at the Dutch informal threshold for cost-effectiveness of
      preventive intervention of EUR 20,000. A sensitivity analysis showed substantial
      uncertainty of ICER values. CONCLUSION: Counseling in combination with pedometer
      use aiming to increase physical activity may be a cost-effective intervention.
      However, the intervention only yields relatively small health benefits in the
      Netherlands.

PMID- 23006468
TI  - Hyaluronan, a ready choice to fuel regeneration: a mini-review.
AB  - BACKGROUND: Hyaluronan (HA) is present in extracellular spaces and interstitia of
      many tissue types. As it is capable of binding high amounts of water, HA provides
      ideal conditions for cell migration and proliferation. Under conditions of
      cellular crowding, it also permits lineage-specific differentiation and thus
      promotes many aspects of healing and tissue remodeling. METHODS: The simplicity
      of its structure makes it amenable to chemical modifications and/or combined
      formulations with other bioactive substances. Thus a wide variety of clinical
      applications have been proposed, several of which are currently being implemented
      in advanced therapies. RESULTS: Known features of HA biology, in particular
      regarding synthesis and processes related to signaling and control, have been
      adopted to elaborate specific products in order to support progress in
      regenerative medicine. Purified HA, HA-based hydrogels or special HA composites
      have been formulated together with other well-characterized biomaterials and
      bioactive factors. HA is currently employed in a variety of therapeutic
      applications both in its pure form and in a biofunctionalized form. CONCLUSIONS:
      HA plays an essential role in regenerative processes. Owing to the growing
      scientific knowledge in this field, medicinal products based on HA have been
      devised and are being routinely applied in ophthalmology or in trauma and
      transplantation surgery. Further areas of application are contemplated, such as
      the use of HA composite scaffold material in tissue engineering, or refined HA
      hydrogels enabling controlled release of medication.

PMID- 23006469
TI  - Risk map and spatial determinants of pancreas disease in the marine phase of
      Norwegian Atlantic salmon farming sites.
AB  - BACKGROUND: Outbreaks of pancreas disease (PD) greatly contribute to economic
      losses due to high mortality, control measures, interrupted production cycles,
      reduced feed conversion and flesh quality in the aquaculture industries in
      European salmon-producing countries. The overall objective of this study was to
      evaluate an effect of potential factors contributing to PD occurrence accounting
      for spatial congruity of neighboring infected sites, and then create quantitative
      risk maps for predicting PD occurrence. The study population included active
      Atlantic salmon farming sites located in the coastal area of 6 southern counties
      of Norway (where most of PD outbreaks have been reported so far) from 1 January
      2009 to 31 December 2010. RESULTS: Using a Bayesian modeling approach, with and
      without spatial component, the final model included site latitude, site density,
      PD history, and local biomass density. Clearly, the PD infected sites were
      spatially clustered; however, the cluster was well explained by the covariates of
      the final model. Based on the final model, we produced a map presenting the
      predicted probability of the PD occurrence in the southern part of Norway.
      Subsequently, the predictive capacity of the final model was validated by
      comparing the predicted probabilities with the observed PD outbreaks in 2011.
      CONCLUSIONS: The framework of the study could be applied for spatial studies of
      other infectious aquatic animal diseases.

PMID- 23006471
TI  - beta-Catenin/Tcf signaling in murine oocytes identifies nonovulatory follicles.
AB  - WNTS are secreted glycoprotein molecules that signal through one of three
      signaling pathways. The best-characterized pathway involves stabilization of the
      multifunctional protein beta-catenin, which in concert with members of the T-cell
      factor (Tcf) family activates specific gene transcription. We have examined
      putative Wnt/beta-catenin in the murine ovary using transgenic mice harboring a
      reporter construct that activates beta-galactosidase (lacZ) expression in
      response to beta-catenin/Tcf binding (TopGal mice). Primordial and primary
      follicles did not stain for lacZ, and the proportion of beta-catenin/Tcf
      signaling oocytes was lower than that of nonsignaling oocytes throughout estrous
      cycle. beta-Catenin/Tcf signaling oocytes were observed in follicles from the
      secondary stage of development and their proportion increased with follicular
      maturation (secondary follicles, 20%; early antral and antral follicles, 70%). In
      contrast, the majority (>90%) of ovulated oocytes did not stain for lacZ. As the
      oocyte possesses components for WNT signal transduction, our data suggest that
      beta-catenin/Tcf signaling is involved in the development of follicular ovulatory
      capability and identifies nonovulatory follicles.

PMID- 23006470
TI  - Identification of resistant carboxylesterase alleles in Culex pipiens complex via
      PCR-RFLP.
AB  - BACKGROUND: Carboxylesterase overproduction is a frequently observed resistance
      mechanism of insects to organophosphate insecticides. As a major transmitter of
      human diseases, mosquitoes in the Culex pipiens complex have evolved 13
      carboxylesterase alleles (Ester) that confer organophosphate resistance. Six
      alleles, Ester(B1), Ester2, Ester8, Ester9, Ester(B10), and Ester11, have been
      observed in field populations in China, sometimes co-existing in one population.
      To differentiate the carboxylesterase alleles found in these field populations,
      PCR-RFLP was designed for use in resistance monitoring. RESULTS: Based on the DNA
      sequences of resistant and nonresistant carboxylesterase alleles, Ester B alleles
      were first amplified with PCR-specific primers and then digested with the
      restriction enzyme DraI. In this step, Ester2 and Ester11 were differentiated
      from the other Ester alleles. When the other Ester B alleles were digested with
      the restriction enzyme XbaI, Ester(B1) and the susceptible C. p. pallens Ester
      were screened out. Ester8 and Ester9 were differentiated from Ester(B10) and the
      susceptible C. p. quinquefasciatus esterase allele, respectively, by amplifying
      and digesting the Ester A alleles with the restriction enzyme ApaLI. The
      effectiveness of the custom-designed PCR-RFLP was verified in two field mosquito
      populations. CONCLUSIONS: A PCR-RFLP based approach was developed to
      differentiate carboxylesterase alleles in Culex pipiens complex mosquitoes. These
      processes may be useful in monitoring the evolutionary dynamics of known
      carboxylesterase alleles as well as in the identification of new alleles in field
      populations.

PMID- 23006472
TI  - Blastomatoid pulmonary carcinosarcoma: report of a case with a review of the
      literature.
AB  - BACKGROUND: Pulmonary carcinosarcoma is a biphasic tumour with an unfavourable
      prognosis. The differential diagnosis includes pulmonary blastoma and is often
      challenging. CASE PRESENTATION: We here describe a case of blastomatoid pulmonary
      carcinosarcoma in a 58-year-old patient, who underwent surgical resection.
      Histopathological examination revealed immature glandular epithelium resembling
      high-grade fetal adenocarcinoma expressing epithelial markers and membranous beta
      catenin, and blastomatoid spindle cells with partial rhabdomyosarcoma-like
      differentiation. Both elements expressed p53, MDM2, and cyclin-dependent kinase 4
      (CDK4), but not thyroid-transcription factor 1 (TTF-1). Mutation analysis of
      KRAS, EGFR, and beta-catenin revealed no mutations. Comparative genomic
      hybridization detected +1q, +6p, +6q24qter, +8q, +11q12q14, +11q23qter,
      +12q12q21, +12q24qter, +17q, +20q, -5q14q23, -9p13pter, -13q21q21, and
      amplifications at 12q14q21, 15q24qter, 20q11q12. CONCLUSION: The observed
      molecular and cytogenetic findings may provide additional tools for the
      differential diagnosis of biphasic pulmonary neoplasms. Furthermore, TP53, MDM2,
      CDK4, and PTPN1 may be involved in tumourigenesis.

PMID- 23006473
TI  - Cyclophosphamide responsive primary angiitis of the CNS in a 61-year-old female.

PMID- 23006474
TI  - Incidental corticobasal degeneration in a 76-year-old woman.

PMID- 23006475
TI  - Axis II comorbidity of borderline personality disorder in adolescents.
AB  - AIMS: The objective of the present study was to explore the comorbidity of
      borderline personality disorder (BPD) with other personality disorders in
      adolescents and compare these comorbidities in male and female subjects. METHODS:
      The sample was drawn from a European research project investigating the
      phenomenology of BPD in adolescence (EURNET BPD). A total of 85 BPD patients (11
      boys and 74 girls) with a mean age of 16.3 years were included in the study.
      RESULTS: According to the results of the Structured Interview for DSM-IV
      Disorders of Personality, obsessive-compulsive (35.3%), antisocial (22.4%),
      avoidant (21.2%), dependent (11.8%) and paranoid (9.4%) personality disorders had
      significant co-occurrences with BPD. Although none of the gender differences was
      statistically significant, we observed a trend towards higher rates of antisocial
      personality disorders in men (45.5%) than in women (19%). CONCLUSION: The study
      results confirmed the frequency of Axis II comorbidity in adolescents with BPD
      and, for the first time, evidenced a differential pattern of comorbidity in males
      and females. This differential pattern must be taken into account when developing
      treatment strategies for adolescents with BPD.

PMID- 23006476
TI  - Electroacupuncture promotes the differentiation of transplanted bone marrow
      mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected
      spinal cord of rats.
AB  - Our previous study indicated that electroacupuncture (EA) could increase
      neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the
      differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and
      improve functional recovery in the injured spinal cord of rats. However, the
      number of neuron-like cells derived from the MSCs is limited. It is known that NT
      3 promotes the survival and differentiation of neurons by preferentially binding
      to its receptor TrkC. In this study, we attempted to transplant TrkC gene
      modified MSCs (TrkC-MSCs) into the spinal cord with transection to investigate
      whether EA treatment could promote NT-3 secretion in the injured spinal cord and
      to determine whether increased NT-3 could further enhance transplanted MSCs
      overexpressing TrkC to differentiate into neuron-like cells, resulting in
      increased axonal regeneration and functional improvement in the injured spinal
      cord. Our results showed that EA increased NT-3 levels; furthermore, it promoted
      neuron-phenotype differentiation, synaptogenesis, and myelin formation of
      transplanted TrkC-MSCs. In addition, TrkC-MSC transplantation combined with EA
      (the TrkC-MSCs + EA group) treatment promoted the growth of the descending BDA
      labeled corticospinal tracts (CSTs) and 5-HT-positive axonal regeneration across
      the lesion site into the caudal cord. In addition, the conduction of cortical
      motor-evoked potentials (MEPs) and hindlimb locomotor function increased as
      compared to controls (treated with the LacZ-MSCs, TrkC-MSCs, and LacZ-MSCs + EA
      groups). In the TrkC-MSCs + EA group, the injured spinal cord also showed
      upregulated expression of the proneurogenic factors laminin and GAP-43 and
      downregulated GFAP and chondroitin sulfate proteoglycans (CSPGs), major
      inhibitors of axonal growth. Together, our data suggest that TrkC-MSC
      transplantation combined with EA treatment spinal cord injury not only increased
      MSC survival and differentiation into neuron-like cells but also promoted CST
      regeneration across injured sites to the caudal cord and functional improvement,
      perhaps due to increase of NT-3 levels, upregulation of laminin and GAP-43, and
      downregulation of GFAP and CSPG proteins.

PMID- 23006477
TI  - High-sensitive cardiac Troponin T is superior to echocardiography in predicting 1
      year mortality in patients with SIRS and shock in intensive care.
AB  - BACKGROUND: Left ventricular (LV) dysfunction is well documented in the
      critically ill. We assessed 1-year mortality in relation to cardiac biomarkers
      and LV function parameters by echocardiography in patients with shock. METHODS: A
      prospective, observational, cohort study of 49 patients. B-natriuretic peptide
      (BNP), high-sensitive troponin T (hsTNT) and transthoracic echocardiography (TTE)
      were assessed within 12 h of study inclusion. LV systolic function was measured
      by ejection fraction (LVEF), mean atrioventricular plane displacement (AVPDm),
      peak systolic tissue Doppler velocity imaging (TDIs) and velocity time integral
      in the LV outflow tract (LVOT VTI). LV diastolic function was evaluated by
      transmitral pulsed Doppler (E, A, E/A, E-deceleration time), tissue Doppler
      indices (e, a, E/e) and left atrial volume (La volume). APACHE II (Acute
      Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure
      Assessment) scores were calculated. RESULTS: hsTNT was significantly higher in
      non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p =
      0.003). Other univariate predictors of mortality were APACHE II (p = 0.009), E/e
      (p = 0.023), SOFA (p = 0.024) and age (p = 0.031). Survivors and non-survivors
      did not differ regarding BNP (p = 0.26) or any LV systolic function parameter
      (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18). Multivariable
      logistic regression analysis identified hsTNT (p = 0.010) as the only independent
      predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2- 3.5).
      CONCLUSIONS: hsTNT was the only independent predictor of 1-year mortality in
      patients with shock. Neither BNP nor echocardiographic parameters had an
      independent prognostic value. Further studies are needed to establish the
      clinical significance of elevated hsTNT in patients in shock.

PMID- 23006478
TI  - Features of proximal and distal excitatory synaptic inputs to layer V neurons of
      the rat medial entorhinal cortex.
AB  - The entorhinal cortex (EC) has a fundamental function in transferring information
      between the hippocampus and the neocortex. EC layer V principal neurons are the
      main recipients of the hippocampal output and send processed information to the
      neocortex, likely playing an important role in memory processing and
      consolidation. Most of these neurons have apical dendrites that extend to the
      superficial layers and are rich in spines, which could be the targets of
      excitatory inputs from fibres innervating that region. We have used electrical
      stimulation of afferent fibres coupled with whole-cell patch-clamp somatic
      recordings to study the features of distal excitatory inputs and compare them
      with those of proximal ones. The amplitude of putative unitary excitatory
      responses was ~1.5 times larger for distal compared with proximal inputs. The
      responses were purely glutamatergic, as they were abolished by a combination of
      AMPA and NMDA glutamatergic receptor antagonists. Blockade of I(h) by 4
      ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride (ZD7288)
      increased temporal summation; the increase was comparable for proximal and distal
      inputs. Proximal inputs initiated a somatic spike more reliably than distal ones;
      in some instances, somatic action potentials triggered by distal stimulation were
      preceded by dendritic spikes that fully propagated to the soma. Altogether, our
      results show that medial layer V entorhinal neurons receive excitatory synapses
      at distal dendritic locations, which gives them access to information encoded by
      inputs to the superficial layers as well as the deep layers. These findings are
      fundamentally relevant to understanding the role of the EC in the formation and
      consolidation of episodic memory.

PMID- 23006356
TI  - Search for pair production of a new b' quark that decays into a Z boson and a
      bottom quark with the ATLAS detector.
AB  - A search is reported for the pair production of a new quark b' with at least one
      b' decaying to a Z boson and a bottom quark. The data, corresponding to 2.0 fb(
      1) of integrated luminosity, were collected from pp collisions at ?s = 7 TeV with
      the ATLAS detector at the CERN Large Hadron Collider. Using events with a b
      tagged jet and a Z boson reconstructed from opposite-charge electrons, the mass
      distribution of large transverse momentum b' candidates is tested for an
      enhancement. No evidence for a b' signal is detected in the observed mass
      distribution, resulting in the exclusion at a 95% confidence level of b' quarks
      with masses m (b') < 400 GeV that decay entirely via b' -> Z+b. In the case of a
      vectorlike singlet b' mixing solely with the third standard model generation,
      masses m(b') < 358 GeV are excluded.

PMID- 23006479
TI  - Oxidative stress contributes to the augmented exercise pressor reflex in
      peripheral arterial disease patients.
AB  - Exaggerated blood pressure (BP) responses to dynamic exercise predict
      cardiovascular mortality in patients with peripheral arterial disease (PAD).
      However, the underlying mechanisms are unclear and no attempt has been made to
      attenuate this response using antioxidants. Three physiological studies were
      conducted in patients with PAD and controls. In Protocol 1, subjects underwent 4
      min of low-intensity (0.5-2.0 kg), rhythmic plantar flexion in the supine
      posture. In Protocol 2, patients with PAD received high-dose ascorbic acid
      intravenously before exercise. In Protocol 3, involuntary exercise was conducted
      via electrical stimulation of the tibial nerve. The primary outcome measure was
      Delta mean arterial pressure (MAP) during the first 20 s of exercise (i.e. the
      onset of sympathoexcitation by muscle afferents). Compared to controls, patients
      with PAD had significantly greater DeltaMAP during plantar flexion, particularly
      at 0.5 kg with the most affected leg (11 +/- 2 vs. 2 +/- 1 mmHg) as well as the
      least affected leg (7 +/- 1 vs. 1 +/- 1 mmHg). This augmented response occurred
      before the onset of claudication pain and was attenuated by ~50% with ascorbic
      acid. Electrically evoked exercise also elicited larger haemodynamic changes in
      patients with PAD compared to controls. Further, the DeltaMAP during 0.5 kg
      plantar flexion inversely correlated with the ankle-brachial index, indicating
      that patients with more severe resting limb ischaemia have a larger BP response
      to exercise. The BP response to low-intensity exercise was enhanced in PAD.
      Chronic limb ischaemia may sensitize muscle afferents and potentiate the BP
      response to muscle contraction in a dose-dependent manner.

PMID- 23006480
TI  - Dihydropyridine receptors actively control gating of ryanodine receptors in
      resting mouse skeletal muscle fibres.
AB  - Contraction of skeletal muscle is triggered by the release of Ca(2+) from the
      sarcoplasmic reticulum (SR) in response to depolarization of the muscle membrane.
      Depolarization is known to elicit a conformational change of the dihydropyridine
      receptor (DHPR) in the tubular membrane that controls in a time- and voltage
      dependent manner the opening of the ryanodine receptor (RyR), the SR Ca(2+)
      release channel. At rest, it is assumed that RyRs are kept in a closed state
      imposed by the repressive action of DHPRs; however, a direct control of the RyR
      gating by the DHPR has up to now never been demonstrated in resting adult muscle.
      In this study, we monitored slow changes in SR Ca(2+) content using the Ca(2+)
      indicator fluo-5N loaded in the SR of voltage-clamped mouse muscle fibres. We
      first show that external Ca(2+) removal induced a reversible SR Ca(2+) efflux at 
      80 mV and prevented SR Ca(2+) refilling following depolarization-evoked SR Ca(2+)
      depletion. The dihydropyridine compound nifedipine induced similar effects. The
      rate of SR Ca(2+) efflux was also shown to be controlled in a time- and voltage
      dependent manner within a membrane potential range more negative than -50 mV.
      Finally, intracellular addition of ryanodine produced an irreversible SR Ca(2+)
      efflux and kept the SR in a highly depleted state following depolarization-evoked
      SR Ca(2+) depletion. The fact that resting SR Ca(2+) efflux is modulated by
      conformational changes of DHPRs induced by external Ca(2+), nifedipine and
      voltage demonstrates that DHPRs exert an active control on gating of RyRs in
      resting skeletal muscle.

PMID- 23006481
TI  - Dietary iodide controls its own absorption through post-transcriptional
      regulation of the intestinal Na+/I- symporter.
AB  - Dietary I(-) absorption in the gastrointestinal tract is the first step in I(-)
      metabolism. Given that I(-) is an essential constituent of the thyroid hormones,
      its concentrating mechanism is of significant physiological importance. We
      recently described the expression of the Na(+)/I(-) symporter (NIS) on the apical
      surface of the intestinal epithelium as a central component of the I(-)
      absorption system and reported reduced intestinal NIS expression in response to
      an I(-)-rich diet in vivo. Here, we evaluated the mechanism involved in the
      regulation of NIS expression by I(-) itself in enterocytes. Excess I(-) reduced
      NIS-mediated I(-) uptake in IEC-6 cells in a dose- and time-dependent fashion,
      which was correlated with a reduction of NIS expression at the plasma membrane.
      Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating
      that an increase in intracellular I(-) regulates NIS. Iodide induced rapid
      intracellular recruitment of plasma membrane NIS molecules and NIS protein
      degradation. Lower NIS mRNA levels were detected in response to I(-) treatment,
      although no transcriptional effect was observed. Interestingly, I(-) decreased
      NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent
      protein-based reporter constructs revealed a significant repressive effect of the
      I(-)-targeting NIS mRNA 3 untranslated region. In conclusion, excess I(-)
      downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our
      data suggest that I(-) regulates intestinal NIS mRNA expression at the post
      transcriptional level as part of an autoregulatory effect of I(-) on its own
      metabolism.

PMID- 23006483
TI  - Evolution of peripheral nerve function in humans: novel insights from motor nerve
      excitability.
AB  - While substantial alterations in myelination and axonal growth have been
      described during maturation, their interactions with the configuration and
      activity of axonal membrane ion channels to achieve impulse conduction have not
      been fully elucidated. The present study utilized axonal excitability techniques
      to compare the changes in nerve function across healthy infants, children,
      adolescents and adults. Multiple excitability indices (stimulus-response curve,
      strength-duration time constant, threshold electrotonus, current-threshold
      relationship and recovery cycle) combined with conventional neurophysiological
      measures were investigated in 57 subjects (22 males, 35 females; age range 0.46
      24 years), stimulating the median motor nerve at the wrist. Maturational changes
      in conduction velocity were paralleled by significant alterations in multiple
      excitability parameters, similarly reaching steady values in adolescence.
      Maturation was accompanied by reductions in threshold (P < 0.005) and rheobase (P
      = 0.001); depolarizing and hyperpolarizing electrotonus progressively reduced (P
      < 0.001), or 'fanned-in'; resting current-threshold slope increased (P < 0.0001);
      accommodation to depolarizing currents prolonged (P < 0.0001); while greater
      threshold changes in refractoriness (P = 0.001) and subexcitability (P < 0.01)
      emerged. Taken together, the present findings suggest that passive membrane
      conductances and the activity of K(+) conductances decrease with formation of the
      axo-glial junction and myelination. In turn, these functional alterations serve
      to enhance the efficiency and speed of impulse conduction concurrent with the
      acquisition of motor skills during childhood, and provide unique insight into the
      evolution of postnatal human peripheral nerve function. Significantly, these
      findings bring the dynamics of axonal development to the clinical domain and
      serve to further illuminate pathophysiological mechanisms that occur during
      development.

PMID- 23006482
TI  - A key circulatory defence against asphyxia in infancy--the heart of the matter!
AB  - A resumption of, and escalation in, breathing efforts (hyperpnoea) reflexively
      accelerates heart rate (HR) and may facilitate cardiac and circulatory recovery
      from apnoea. We analysed whether this mechanism can produce a sustained rise in
      HR (tachycardia) when a sleeping infant is confronted by mild, rapidly worsening
      asphyxia, simulating apnoea. Twenty-seven healthy term-born infants aged 1-8 days
      rebreathed the expired gas for 90 s during quiet sleep to stimulate breathing and
      heart rate. To discriminate cardio-excitatory effects of central respiratory
      drive, lung inflation, hypoxia, hypercapnia and asphyxia, we varied the inspired
      O(2) level and compared temporal changes in response profiles as respiratory
      sensitivity to hypoxia and asphyxia 'reset' after birth. We demonstrate that
      asphyxia-induced hyperpnoea and tachycardia strengthen dramatically over the
      first week with different time courses and via separate mechanisms. Cardiac
      excitation by hypercapnia improves first, followed by a slower improvement in
      respiratory hypoxic drive. A rise in CO(2) consequently elicits stronger, longer
      lasting tachycardia than moderate increases in respiratory drive or lung
      expansion. We suggest that without a strong facilitating action of CO(2) on the
      immature heart, respiratory manoeuvres may be unable to reflexively counteract
      strong vagal bradycardia. This may increase the vulnerability of some infants to
      apnoea-asphyxia.

PMID- 23006484
TI  - Regulatory roles of the NMDA receptor GluN3A subunit in locomotion, pain
      perception and cognitive functions in adult mice.
AB  - Since the discovery of the glutamate NMDA receptor subunit 3A (GluN3A), the
      functional role of this unique inhibitory subunit has been largely obscure.
      GluN3A expression is high in the neonatal brain but declines to a low level in
      the adult brain; it is thus commonly believed that GluN3A does not have a major
      functional impact in adulthood. Using wild-type (WT) and GluN3A knockout (KO)
      mice, we show here that deletion of GluN3A affected multiple behavioural
      functions in adult animals. GluN3A KO mice showed impaired locomotor activity on
      a variety of motor function tests, and increased sensitivity to acute and sub
      acute inflammatory pain. GluN3A KO mice also showed enhanced recognition and
      spatial learning and memory functions. Hippocampal slices from juvenile and adult
      GluN3A KO mice showed greater long-term potentiation (LTP) compared with WT
      slices. GluN3A deletion resulted in increased expression of Ca(2+)/calmodulin
      dependent kinase II (CaMKII) in the forebrain, and the phosphorylated CaMKII
      level upon LTP induction was significantly higher in the GluN3A KO hippocampus
      compared with WT controls. CaMKII inhibition abrogated the enhanced LTP in GluN3A
      KO slices. These data reveal for the first time that the presence of GluN3A may
      have profound impacts on several functional/behavioural activities in adult
      animals, and could be a therapeutic target for neurological disorders associated
      with NMDA receptor functions.

PMID- 23006485
TI  - Genetic and pharmacological modulation of giant depolarizing potentials in the
      neonatal hippocampus associates with increased seizure susceptibility.
AB  - The expression of Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is responsible for high
      intracellular Cl(-) resulting in the excitatory action of GABA(A) receptor
      activation in the developing brain. Giant depolarizing potentials (GDPs) are
      spontaneous network oscillations that involve GABA(A) receptors and are thought
      to be important in establishing neuronal circuit wiring. Earlier work established
      that seizure susceptibility in the GABA(A) gamma2(R43Q) epilepsy mouse is
      impacted by developmental consequences of impaired GABA(A) receptor function. We
      investigated the potential mechanism of the developmental influence by recording
      GDPs in the CA3 pyramidal neurons from brain slices of the neonatal GABA(A)
      gamma2(R43Q) mouse. Interestingly, the number of GPDs was significantly lower in
      slices from mutant mouse compared with wild-type control, suggesting an
      involvement in setting seizure susceptibility. To test this idea we blocked NKCC1
      with bumetanide in neonatal mice and reduced the number of GDPs to a level
      similar to that seen in the mutant mice. We found that neonatal treatment with
      bumetanide resulted in a similar level of susceptibility to thermally induced
      seizures as described for the GABA(A) gamma2(R43Q) mouse. These results provide
      evidence that a human GABA(A) receptor epilepsy mutation exerts a developmental
      influence by modulating the number of GDPs. It also draws attention to the
      potential risk of early treatment with bumetanide.

PMID- 23006486
TI  - Does human leukocyte elastase degrade intact skin elastin?
AB  - This study aimed to investigate the susceptibility of intact fibrillar human
      elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein
      of the extracellular matrix of vertebrates, and provides exceptional properties
      including elasticity and tensile strength to many tissues and organs, including
      the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for
      their long-term function. Mature elastin is an insoluble and extremely durable
      protein that undergoes very little turnover, but sustained exposure to proteases
      may lead to irreversible and severe damage, and thus to functional loss of the
      elastic fiber network. Hence, it is a key issue to understand which enzymes
      actually initiate elastolysis under certain pathological conditions or during
      intrinsic aging. In this paper, we provide a complete workflow for isolation of
      pure and intact elastin from very small tissue samples to test enzymes for their
      elastolytic potential. This workflow was applied to skin samples from variously
      aged individuals, and it was found that strong differences exist in the
      degradability of the elastins investigated. In summary, human leukocyte elastase
      was unable to degrade intact elastin fibers but hydrolyzed elastin derived from
      the skin of old people. However, cathepsin G cleaved all elastin samples, even
      those derived from younger individuals. These results indicate that human
      leukocyte elastase is not a driving force for elastolysis, but may nevertheless
      promote further breakdown of elastic fibers after the action of other enzymes
      such as cathepsin G.

PMID- 23006487
TI  - Long-term histologic changes and effects of perichondrium preservation of
      auricular cartilage grafted in rabbit tympanic bullae.
AB  - INTRODUCTION: This study evaluated the long-term histologic changes of grafted
      auricular cartilage in rabbit tympanic bullae. MATERIALS AND METHODS: Auricular
      cartilage with or without perichondrium was prepared and cut into small pieces to
      obliterate the rabbit tympanic bullae. The histologic changes of the grafted
      cartilage in both groups were compared 20 months after surgery. RESULTS:
      Remarkable spongy bony trabeculae of mature lamellar bone with red bone marrow
      formation were observed in the perichondrium-preserved group. Parts of the
      grafted cartilage pieces were invaded and replaced by bone and bone marrow. The
      grafted cartilage pieces grossly maintained their original polygonal shapes, and
      no osteochondral tissue regeneration was observed in the perichondrium-removed
      group. The viable chondrocyte ratios were 46.21 +/- 5.58 versus 27.80 +/- 4.81%,
      and the minimal resorption ratios were 10.31 +/- 3.27 versus 2.98 +/- 1.48% in
      the perichondrium-preserved (n = 14) and -removed groups (n = 12, p < 0.05). The
      tissue ratios were cartilage: 38.18 +/- 8.76 versus 52.97 +/- 9.30%; lamellar
      bone: 18.49 +/- 5.31 versus 0.82 +/- 0.43%; bone marrow: 20.72 +/- 6.27 versus
      0.00 +/- 0.00%; fibrous tissue: 10.13 +/- 2.74 versus 5.81 +/- 2.20%, and adipose
      tissue: 12.01 +/- 4.48 versus 40.70 +/- 7.83% in the perichondrium-preserved and 
      removed groups. The differences were all statistically significant (p < 0.05).
      CONCLUSION: A space-filling mass effect with minimal resorption of the cartilage
      pieces was observed in the perichondrium-removed group. In addition to this mass
      effect, the progenitor cells in the preserved perichondrium allowed active bone
      tissue regeneration and cartilage resorption in the perichondrium-preserved
      group.

PMID- 23006489
TI  - Cost-effectiveness of cardiac resynchronization therapy: perspective from
      Argentina.
AB  - OBJECTIVES: Cardiac resynchronization therapy (CRT) has recently been shown to
      reduce both mid-term and long-term mortality in patients with mild heart failure.
      Although proven effective, it is unclear whether CRT is cost-effective in low and
      middle-income countries (LMIC). Therefore, we set out to analyze the cost
      effectiveness of CRT in Argentina in patients with New York Heart Association
      (NYHA) functional class (FC) I or II heart failure (HF). We chose to compare
      patients receiving optimal medical treatment (OMT) and CRT with those patients
      receiving only OMT. METHODS: We constructed a Markov model with a cohort
      simulation, and a life-time horizon to assess costs, life-years, and quality
      adjusted life-year (QALY) gained as a result of treatment with both CRT and OMT
      from an Argentine third party payer perspective. We included patients who met the
      following criteria: left ventricular ejection fraction (LVEF) <= 40 percent,
      sinus rhythm with a QRS >= 120 msec, and NYHA FC I-II HF. The results were
      expressed as cost per life-year and QALY gained in international dollars (ID$)
      for the year 2009. RESULTS: For the base case analysis performed, we started at a
      fixed age of 65. After applying a 3 percent annual discount rate, the incremental
      cost-effectiveness ratio (ICER) was 38.005 ID$ per year of life gained and 34.185
      ID$ per QALY gained. CONCLUSIONS: Long-term treatment with CRT appears to be cost
      effective in Argentina compared with patients treated solely with OMT. Similar
      analysis should be performed to determine if this treatment option is cost
      effective in other LMIC.

PMID- 23006488
TI  - Cryptic diversity in flathead fishes (Scorpaeniformes: Platycephalidae) across
      the Indo-West Pacific uncovered by DNA barcoding.
AB  - Identification of taxonomical units underpins most biological endeavours ranging
      from accurate biodiversity estimates to the effective management of sustainably
      harvested, protected or endangered species. Successful species identification is
      now frequently based on a combination of approaches including morphometrics and
      DNA markers. Sequencing of the mitochondrial COI gene is an established
      methodology with an international campaign directed at barcoding all fishes. We
      employed COI sequencing alongside traditional taxonomic identification methods
      and uncovered instances of deep intraspecific genetic divergences among flathead
      species. Sixty-five operational taxonomic units (OTUs) were observed across the
      Indo-West Pacific from just 48 currently recognized species. The most
      comprehensively sampled taxon, Platycephalus indicus, exhibited the highest
      levels of genetic diversity with eight lineages separated by up to 16.37% genetic
      distance. Our results clearly indicate a thorough reappraisal of the current
      taxonomy of P. indicus (and its three junior synonyms) is warranted in
      conjunction with detailed taxonomic work on the other additional Platycephalidae
      OTUs detected by DNA barcoding.

PMID- 23006490
TI  - Family-based and case-control study of glutamate receptor GRIK3 Ser310Ala
      polymorphism in alcohol dependence.
AB  - AIM: The aim of this study was to evaluate the role of the glutamate receptor
      subunit-7 (GluR7, GRIK 3) rs6691840 (Ser310Ala, T928G) in the pathogenesis of
      alcohol dependence (AD). METHODS: DNA was provided from AD patients (n = 209) and
      healthy control subjects (n = 308) all of Polish descent. The history of
      alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured
      Assessment for the Genetics of Alcoholism). We conducted case-control association
      study and transmission disequilibrium test (TDT). GRIK3 functional polymorphism
      was genotyped by the PCR-RFLP method. RESULTS: Analyses revealed that
      polymorphism Ser310Ala of GRIK3 gene is not associated with AD or any of its
      subgroups. TDT reveled an adequate transmission of both alleles in the group of
      alcohol families. CONCLUSIONS: These findings replicate and extend our previous
      research results that do not support the hypothesis of the role of rs6691840 in
      the pathogenesis of AD.

PMID- 23006493
TI  - Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating
      with disease severity.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficiency is
      caused by one or more mutations in the G6PD gene on chromosome X. An association
      between enzyme levels and gene haplotypes remains to be established. METHODS: In
      this study, we determined G6PD enzyme levels and sequenced the coding region,
      including the intron-exon boundaries, in a group of individuals (163 males and 86
      females) who were referred to the clinic with suspected G6PD deficiency. The
      sequence data were analysed by physical linkage analysis and PHASE haplotype
      reconstruction. RESULTS: All previously reported G6PD missense changes, including
      the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our
      cohort. The AURES mutation (p.Ile48Thr) was the most common variant in the cohort
      (30% in males patients) followed by the Mediterranean variant (p.Ser188Phe)
      detectable in 17.79% in male patients. Variant forms of the A- mutation
      (p.Val68Met, p.Asn126Asp or a combination of both) were detectable in 15.33% of
      the male patients. However, unique to this study, several of such mutations co
      existed in the same patient as shown by physical linkage in males or PHASE
      haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD,
      13 different haplotypes (13 in males, 8 in females) were identified. Five of
      these were previously unreported (Jeddah A, B, C, D and E) and were defined by
      previously unreported combinations of extant mutations where patients harbouring
      these haplotypes exhibited severe G6PD deficiency. CONCLUSIONS: Our findings will
      help design a focused population screening approach and provide better management
      for G6PD deficiency patients.

PMID- 23006494
TI  - Test-retest reliability of transport-related physical activity performed during
      the lifetime.
AB  - BACKGROUND: One of the convenient ways to achieve recommended levels of physical
      activity is through 'active transport,' such as walking or cycling to and from
      work or school. Although studies have shown that participants can reliably recall
      information about recent transport-related physical activity, it is not known if
      the reliability remains high when asking about lifetime behavior. This study
      tested the reliability of questions that collect information about transport
      related physical activity performed over the lifetime. METHODS: Participants were
      asked to complete self-administered questions about transport-related physical
      activity on 2 separate occasions. The questions asked about cycling and walking
      to and from work and/or school during 3 age periods: 15-24 years, 25-39 years,
      and 40 years and above. A lifetime average was also calculated for cycling,
      walking, and total activity. RESULTS: There was fair to good test-retest
      reliability of the age-period specific questions for transport-related cycling
      (ICCs from 0.65-0.74), walking (ICCs from 0.44-0.58), and total activity (ICCs
      from 0.57-0.66). The reliability of the lifetime averages were also fair to good
      (ICCs from 0.58-0.70). CONCLUSIONS: The questions tested in this study have
      moderate reliability, and appear to be useful questions for measuring lifetime
      transport-related physical activity.

PMID- 23006495
TI  - Are there anthropometric differences between autistic and healthy children?
AB  - Anthropometric development and growth were assessed in 2 groups of 6- to 9-year
      olds: children with autism spectrum disorders and typically developing children.
      In a case-control study conducted in Valencia, Spain, we compared the body mass
      index (kg/m(2)) of 40 children with autism spectrum disorders (cases) and 113
      typically developing children (controls) from the same area of residence. The sex
      and age-adjusted odds ratios for being underweight in cases was 2.41 compared to
      controls. Furthermore, the body mass index distribution of the cases was
      significantly offset to lower values with respect to that of the controls (P =
      .024). In particular, 20% of the cases had a body mass index below the fifth
      percentile versus just 8.85% of the controls. Our data suggest that the
      anthropometric development of children with autism spectrum disorders should be
      monitored as part of routine care. 

PMID- 23006492
TI  - Genetic diversity in widespread species is not congruent with species richness in
      alpine plant communities.
AB  - The Convention on Biological Diversity (CBD) aims at the conservation of all
      three levels of biodiversity, that is, ecosystems, species and genes. Genetic
      diversity represents evolutionary potential and is important for ecosystem
      functioning. Unfortunately, genetic diversity in natural populations is hardly
      considered in conservation strategies because it is difficult to measure and has
      been hypothesised to co-vary with species richness. This means that species
      richness is taken as a surrogate of genetic diversity in conservation planning,
      though their relationship has not been properly evaluated. We tested whether the
      genetic and species levels of biodiversity co-vary, using a large-scale and multi
      species approach. We chose the high-mountain flora of the Alps and the
      Carpathians as study systems and demonstrate that species richness and genetic
      diversity are not correlated. Species richness thus cannot act as a surrogate for
      genetic diversity. Our results have important consequences for implementing the
      CBD when designing conservation strategies.

PMID- 23006496
TI  - Primary and secondary central nervous system vasculitis.
AB  - Central nervous system vasculitis is an increasingly recognized inflammatory
      brain disease causing devastating neurological deficits and psychiatric
      manifestations in previously healthy children. Primary central nervous system
      vasculitis represents an isolated inflammatory attack targeting the cerebral
      vessels. In contrast, in children with secondary central nervous system
      vasculitis, an underlying condition can be identified. The spectrum of childhood
      primary and secondary central nervous system vasculitis is rapidly expanding, as
      is the differential diagnosis including nonvasculitic inflammatory brain diseases
      and noninflammatory vasculopathies. Early recognition, rapid diagnostic
      evaluation, and initiation of treatment have led to improved morbidity and
      mortality. This review focuses on clinical, laboratory, and neuroimaging
      characteristics of the distinct subtypes of primary childhood central nervous
      system vasculitis, reports the etiology of secondary central nervous system
      vasculitis, provides an overview of the differential diagnosis, and reviews the
      current approaches in treatment.

PMID- 23006491
TI  - SASLT practice guidelines: management of hepatitis C virus infection.

PMID- 23006497
TI  - Fertility preservation and pregnancy in women with and without BRCA mutation
      positive breast cancer.
AB  - Women with breast cancer face many challenges when considering fertility
      preservation. Delayed referral results in the limitation of fertility
      preservation options because most established methods, such as embryo and oocyte
      cryopreservation, require several weeks to complete. Women with BRCA mutations,
      on the other hand, may be more aware of fertility issues and motivated to see
      fertility preservation specialists earlier. Fear of exposure to estrogen limits
      access to fertility preservation via embryo or oocyte cryopreservation; however,
      the use of aromatase inhibitors as ovarian stimulants reduces such concern.
      Ovarian cryopreservation can be used when there is insufficient time to perform
      ovarian stimulation because this technique does not require hormonal stimulation,
      but there are safety concerns both in women with BRCA mutations and in patients
      with hormone receptor-positive disease as well. There does not seem to be a
      proven ovarian suppression strategy to preserve fertility in women with breast
      cancer. Pregnancy appears to be safe for breast cancer survivors but studies
      specific for women with BRCA mutations are lacking. Women with BRCA mutations may
      elect to use preimplantation genetic diagnosis during in vitro fertilization to
      avoid transmitting the mutation, but there may be psychosocial difficulties in
      entertaining this option. Overall, the last decade has brought many options for
      women with breast cancer considering fertility preservation, but numerous
      challenges remain. The presence of BRCA mutations further contributes to these
      challenges.

PMID- 23006499
TI  - Physics of bandgap formation in Cu-Sb-Se based novel thermoelectrics: the role of
      Sb valency and Cu d levels.
AB  - In this paper we discuss the results of ab initio electronic structure
      calculations for Cu(3)SbSe(4) (Se4) and Cu(3)SbSe(3) (Se3), two narrow bandgap
      semiconductors of thermoelectric interest. We find that Sb is trivalent in both
      the compounds, in contrast to a simple nominal valence (ionic) picture which
      suggests that Sb should be 5 + in Se4. The gap formation in Se4 is quite subtle,
      with hybridization between Sb 5s and the neighboring Se 4s, 4p orbitals, position
      of Cu d states, and non-local exchange interaction, each playing significant
      roles. Thermopower calculations show that Se4 is a better p-type system. Our
      theoretical results for Se4 agree very well with recent experimental results
      obtained by Skoug et al (2011 Sci. Adv. Mater. 3 602).

PMID- 23006498
TI  - Phase I study and biomarker analysis of lapatinib and concurrent radiation for
      locally advanced breast cancer.
AB  - PURPOSE: This phase I study assessed the toxicity and safety of combining daily
      lapatinib with radiation therapy. Sequential tumor biopsies were obtained to
      evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR)
      and human EGFR-2 (HER2) signaling pathways. METHODS: Eligibility for this dose
      escalation study included unresectable and locally recurrent or chemotherapy
      refractory and locally advanced breast cancer, and adequate organ function.
      Patients underwent three serial biopsies: at baseline, after 1 week of lapatinib
      alone, and after 1 week of lapatinib and radiation. Endpoints included
      determination of toxicity, maximum tolerated dose, and analysis of the effect of
      lapatinib with or without radiation on EGFR and HER2 signaling pathways by
      immunohistochemistry. RESULTS: Doses of lapatinib up to 1,500 mg/day were well
      tolerated. Toxicity of grade 3 or more was limited to radiation dermatitis and
      pain. Out of 19 patients treated, in field responses per response evaluation
      criteria in solid tumors criteria were complete in four patients and partial in
      six patients. Serial biopsies were obtained in 16 patients with no complications.
      Total Her2 was relatively unchanged while phospho-Her2, phospho-Akt, and phospho
      ERK showed variable responses to both lapatinib alone and dual therapy with
      lapatinib and radiation. CONCLUSIONS: The combination of lapatinib and radiation
      was well tolerated in this patient cohort. Overall local response rates were
      comparable to those reported in other studies in this patient population.
      Biopsies were safely performed at all time points. Inhibition of HER2 and
      downstream signaling pathways was identified, although no strong correlation with
      response was seen.

PMID- 23006500
TI  - The dental cavities of equine cheek teeth: three-dimensional reconstructions
      based on high resolution micro-computed tomography.
AB  - BACKGROUND: Recent studies reported on the very complex morphology of the pulp
      system in equine cheek teeth. The continuous production of secondary dentine
      leads to distinct age-related changes of the endodontic cavity. Detailed
      anatomical knowledge of the dental cavities in all ages is required to explain
      the aetiopathology of typical equine endodontic diseases. Furthermore, data on
      mandibular and maxillary pulp systems is in high demand to provide a basis for
      the development of endodontic therapies. However, until now examination of the
      pulp cavity has been based on either sectioned teeth or clinical computed
      tomography. More precise results were expected by using micro-computed tomography
      with a resolution of about 0.1 mm and three-dimensional reconstructions based on
      previous greyscale analyses and histological verification. The aim of the present
      study was to describe the physiological configurations of the pulp system within
      a wide spectrum of tooth ages. RESULTS: Maxillary teeth: All morphological
      constituents of the endodontic cavity were present in teeth between 4 and 16
      years: Triadan 06s displayed six pulp horns and five root canals, Triadan 07-10s
      five pulp horns and four root canals and Triadan 11s seven pulp horns and four to
      six root canals. A common pulp chamber was most frequent in teeth <=5 years, but
      was found even in a tooth of 9 years. A large variety of pulp configurations was
      observed within 2.5 and 16 years post eruption, but most commonly a separation
      into mesial and distal pulp compartments was seen. Maxillary cheek teeth showed
      up to four separate pulp compartments but the frequency of two, three and four
      pulp compartments was not related to tooth age (P > 0.05). In Triadan 06s, pulp
      horn 6 was always connected to pulp horns 1 and 3 and root canal I. In Triadan
      11s, pulp horns 7 and 8 were present in variable constitutions. Mandibular teeth:
      A common pulp chamber was present in teeth up to 15 years, but most commonly seen
      in teeth <=5 years. A segmented pulp system was found in 72% of the investigated
      teeth. Segmentation into separate mesial and distal pulp compartments was most
      commonly present. Pulp horn 4 coalesced either with the mesial pulp horns 1 and 3
      or with the distal pulp horns 2 and 5. CONCLUSIONS: Details of the pulpar anatomy
      of equine cheek teeth are provided, supporting the continuous advancement in
      endodontic therapy. Numerous individual configurations of the pulp system were
      obtained in maxillary cheek teeth, but much less variability was seen in
      mandibular cheek teeth.

PMID- 23006501
TI  - Prospective relationship of duration of untreated psychosis to psychopathology
      and functional outcome over 12 years.
AB  - BACKGROUND: The duration of untreated psychosis is well recognised as an
      independent predictor of symptomatic and functional outcome in the short term and
      has facilitated the development of worldwide early intervention programmes.
      However, the extent and mechanisms by which it might influence prognosis beyond a
      decade remain poorly understood. METHODS: The authors examined the relationship
      between duration of untreated psychosis and outcome 12years after a first episode
      of psychosis and assessed whether its relationship with function is affected by
      symptoms in a prospective, 12-year follow-up of an epidemiologically-based
      inception cohort. RESULTS: Longer duration of untreated psychosis predicted
      poorer remission status, more severe positive and negative symptoms, and greater
      impairment in general functioning, social functioning and quality of life at
      12years on standardised measures, independent of other factors at baseline. It
      was not associated with gainful employment, for which education was the only
      predictor, or independent living, for which age was the only predictor. The
      relationship between duration of untreated psychosis and functional outcome was
      mediated by concurrent psychopathology, particularly negative symptoms.
      CONCLUSIONS: These results provide qualified support for the potential long-term
      benefit of reduction in the duration of untreated psychosis in terms of
      improvement in symptoms and functional outcome. Its failure to predict real-life
      outcomes such as independent living and gainful employment could reflect the
      importance of pre-existing socio-cultural factors such as individual opportunity.
      The relationship between duration of untreated psychosis and negative symptoms
      was largely responsible for its effect on function, suggesting a possible long
      term protective mechanism against disability.

PMID- 23006502
TI  - The effects of insertion speed on inner ear function during cochlear
      implantation: a comparison study.
AB  - OBJECTIVE: To investigate the insertion speed and its impact on electrode
      insertion characteristics, hearing preservation and clinical vestibular function
      in a prospective cohort study with a retrospective control group at a tertiary
      otology/neurotology centre. INTERVENTIONS: Hearing-preserving cochlear
      implantation using systemic and topical steroids in conjunction with a round
      window approach, a complete cochlear coverage electrode and two different
      electrode insertion speeds [60 mm/min (n = 18) vs. 15 mm/min (n = 22)] was
      performed. RESULTS: The insertion speed had a significant impact on various
      insertion characteristics as well as hearing preservation and vestibular
      function. In conclusion, a slow electrode insertion speed appears to facilitate
      full electrode insertion, reduce the occurrence of insertion resistance as well
      as promote preservation of residual hearing and vestibular function after
      cochlear implantation.

PMID- 23006504
TI  - Cerebral sparganosis in children: epidemiological, clinical and MR imaging
      characteristics.
AB  - BACKGROUND: Cerebral sparganosis in children is an extremely rare disease of
      central nervous system, and caused by a tapeworm larva from the genus of
      Spirometra. In this study, we discussed and summarized epidemiological, clinical
      and MR imaging characteristics of eighteen children with cerebral sparganosis for
      a better diagnosis and treatment of the disease. METHODS: Eighteen children with
      cerebral sparganosis verified by pathology, serological tests and MR
      presentations were retrospectively investigated, and the epidemiologic and
      clinical characteristics of the disease were studied. RESULTS: Twenty-seven
      lesions were found in the eighteen children. Twelve lesions in twelve patients
      were solitary while the lesions in the rest six patients were multiple and
      asymmetrical. The positions of the lesions were: seven in frontal, eleven in
      parietal, four in temporal and two in occipital lobes, one in basal ganglia, one
      in cerebella hemisphere and one in pons. The lesions were presented as slight
      hypointensity on T1-weighted images but moderate hyperintensity on T2-weighted
      images with perilesional brain parenchyma edema. Enhanced MR scans by using
      Gadopentetic Acid Dimeglumine Salt were performed in the patients, and the images
      demonstrated abnormal enhancements with the patterns of a peripheral ring, or a
      tortuous beaded, or a serpiginous tubular shape. Follow-up MR scans were
      preformed for eight patients, and three out of the eight cases exposed migrations
      and changes in shapes of the lesion areas. CONCLUSIONS: The MR presentations in
      our study in general were similar to those in previous studies. However
      serpiginous tubular and comma-shaped enhancements of lesions have not been
      previously reported. The enhanced MR imaging and follow-up MR scans with the
      positive results from serological tests are the most important methods for the
      clinical diagnosis of cerebral sparganosis in children.

PMID- 23006505
TI  - Heart rate recovery and variability following combined aerobic and resistance
      exercise training in adults with and without Down syndrome.
AB  - Persons with Down syndrome (DS) are at high risk for cardiovascular morbidity and
      mortality, and there is compelling evidence of autonomic dysfunction in these
      individuals. The main purpose of this study was to determine whether a combined
      aerobic and resistance exercise intervention produces similar results in cardiac
      autonomic function between adults with and without DS. Twenty-five participants
      (13 DS; 12 non-DS), aged 27-50 years, were included. Aerobic training was
      performed 3 days/week for 30 min at 65-85% of peak oxygen uptake (VO(2peak)).
      Resistance training was prescribed for 2 days/week and consisted of two rotations
      in a circuit of 9 exercises at 12-repetition-maximum. There was a significant
      improvement in the VO(2peak) and muscle strength of participants with and without
      DS after training. Heart rate recovery improved at 1 min post-exercise, but only
      in participants with DS. Both groups of participants exhibited a similar increase
      in normalized high frequency power and of decrease in normalized low frequency
      power after training. Therefore, 12 weeks of exercise training enhanced the heart
      rate recovery in adults with DS, but not in those without DS. Contrasting, the
      intervention elicited similar gains between groups for cardiovagal modulation.

PMID- 23006506
TI  - An 11-year and 10-month-old girl with purpura and chest pain.
AB  - Mucosa-associated lymphoid tissue lymphoma (MALToma) is a type of B-cell
      lymphoma. Case reports of childhood thymic MALToma and its association with
      vasculitis are rarely found in the related literature. Herein, we present a
      report of an 11-year and 10-month-old girl who was initially diagnosed with
      cutaneous vasculitis characterized by nonthrombocytopenic palpable purpura,
      positive antinuclear antibody and anti-SSA (Ro) antibody. Eight months later, a
      thymic mediastinal mass was found. Surgical excision was performed and results of
      pathological analysis revealed an extranodal marginal zone CD20(+) B-cell
      MALToma. Benign response to the chemotherapeutic regimen of Berlin-Frankfurt
      Munster group NHL-BFM 90 R2 without relapse was noted in 2 years of follow-up.
      For the first time, our case demonstrated some clinical evidence of the
      association between vasculitis and childhood MALToma. 

PMID- 23006507
TI  - Treatment of epidermal growth factor receptor inhibitor-induced acneiform
      eruption with topical recombinant human epidermal growth factor.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors have been used as
      anticancer agents for the treatment of a variety of solid tumors. Related skin
      toxicities are the most common adverse effects and occur with all EGFR
      inhibitors. Several treatment approaches, such as antiseptic soaps, topical and
      oral antibiotics, and topical and oral corticosteroids, have been reported;
      however, the responses have been varied. Acneiform eruption induced by EGFR
      inhibitor treatment results from disturbed normal keratinocyte and hair follicle
      biology and may therefore benefit from local restoration of EGF pathway.
      OBSERVATIONS: We treated HaCaT cells with EGFR inhibitor and evaluated the
      expression of EGFR. After treatment of cells with EGFR inhibitor, EGFR expression
      was increased in a dose-dependent manner. We hypothesized that newly synthesized
      EGFR, not inhibited by EGFR inhibitors, may perform their biological action in
      keratinocytes in the presence of additional EGF. In this study, we therefore
      treated acneiform eruption patients with topical recombinant human EGF (rhEGF)
      with institutional review board approval. Here, we report three cases of such
      eruptions who responded to topical rhEGF. CONCLUSION: Topical rhEGF may be an
      effective treatment option for EGFR inhibitor-induced acneiform eruption.

PMID- 23006508
TI  - Determinants of seeking treatment for cocaine abuse: a case-control study.
AB  - The objective of this study, which targeted long-term socially integrated cocaine
      users (in powder form, no heroin), was to analyze potential determinants of
      request for treatment for primary cocaine abuse. Two hundred and twenty-three
      cases (users who sought treatment for primary cocaine abuse) and 223 controls
      (users who did not seek treatment) were interviewed in Italy. A semistructured
      interview was created. Conditional logistic regression models were used. Cases
      had begun consuming illicit substances later, started using cocaine quicker, had
      high-risk drinking habits, had more intense recent use of cocaine, and used alone
      and at work. Some of the motivations of use that characterize subjects who seek
      treatment (to experience a 'high', disinhibition, avoidance, and to feel more
      confident) seem specifically to obtain immediate gratification, without concern
      for future consequences. Variability in cocaine abusers seeking treatment has
      been a long-recognized feature of this population and the results show that the
      appropriate target population (cocaine users experiencing problems and using more
      frequently) is reached by treatment services.

PMID- 23006509
TI  - Isolation of mesenchymal stem cells from shoulder rotator cuff: a potential
      source for muscle and tendon repair.
AB  - The self-healing potential of each tissue belongs to endogenous stem cells
      residing in the tissue; however, there are currently no reports mentioned for the
      isolation of human rotator cuff-derived mesenchymal stem cells (RC-MSCs) since.
      To isolate RC-MSCs, minced rotator cuff samples were first digested with enzymes
      and the single cell suspensions were seeded in plastic culture dishes. Twenty
      four hours later, nonadherent cells were removed and the adherent cells were
      further cultured. The RC-MSCs had fibroblast-like morphology and were positive
      for the putative surface markers of MSCs, such as CD44, CD73, CD90, CD105, and
      CD166, and negative for the putative markers of hematopoietic cells, such as
      CD34, CD45, and CD133. Similar to BM-MSCs, RC-MSCs were demonstrated to have the
      potential to undergo osteogenic, adipogenic, and chondrogenic differentiation.
      Upon induction in the defined media, RC-MSCs also expressed lineage-specific
      genes, such as Runx 2 and osteocalcin in osteogenic induction, PPAR-gamma and LPL
      in adipogenic differentiation, and aggrecan and Col2a1 in chondrogenic
      differentiation. The multipotent feature of RC-MSCs in the myogenic injury model
      was further strengthened by the increase in myogenic potential both in vitro and
      in vivo when compared with BM-MSCs. These results demonstrate the successful
      isolation of MSCs from human rotator cuffs and encourage the application of RC
      MSCs in myogenic regeneration.

PMID- 23006510
TI  - Dog ownership and physical activity: a review of the evidence.
AB  - BACKGROUND: Dog walking is a strategy for increasing population levels of
      physical activity (PA). Numerous cross-sectional studies of the relationship
      between dog ownership and PA have been conducted. The purpose was to review
      studies comparing PA of dog owners (DO) to nondog owners (NDO), summarize the
      prevalence of dog walking, and provide recommendations for research. METHODS: A
      review of published studies (1990-2010) examining DO and NDO PA and the
      prevalence of dog walking was conducted (N = 29). Studies estimating the
      relationship between dog ownership and PA were grouped to create a point-
      estimate using meta-analysis. RESULTS: Most studies were conducted in the last 5
      years, were cross-sectional, and sampled adults from Australia or the United
      States. Approximately 60% of DO walked their dog, with a median duration and
      frequency of 160 minutes/week and 4 walks/week, respectively. Meta-analysis
      showed DO engage in more walking and PA than NDO and the effect sizes are small
      to moderate (d = 0.26 and d = 0.16, respectively). Three studies provided
      evidence of a directional relationship between dog ownership and walking.
      CONCLUSIONS: Longitudinal and interventional studies would provide stronger
      causal evidence for the relationship between dog ownership and PA. Improved
      knowledge of factors associated with dog walking will guide intervention
      research.

PMID- 23006511
TI  - Prevalence and risk factors of low bone mineral density in Chinese patients with
      systemic sclerosis: a case-control study.
AB  - OBJECTIVE: To study the prevalence and risk factors of low BMD in patients with
      SSc. METHODS: Consecutive patients with SSc and an equal number of age- and
      gender-matched healthy subjects were screened for BMD, fat and lean mass by DXA
      scan. BMD, body composition and osteoporosis risk factors were compared between
      patients and controls. Associated factors for low BMD in SSc patients were
      studied by linear regression. RESULTS: A total of 84 patients with SSc were
      studied [89% women; age 49.4 (11.3) years; 21% diffuse subtype; disease duration
      7.8 (6.4) years]. Except for significantly lower BMI (P = 0.001), fat mass (P =
      0.02) and lean body mass (P = 0.006) observed in SSc patients, the prevalence of
      other osteoporosis risk factors was similar to controls. Fourteen (17%) and five
      (6%) SSc patients had low BMD expected for age (z-score <-2.0) at the lumbar
      spine and hip, respectively. BMD of the lumbar spine, hip, femoral neck and whole
      body was significantly lower in SSc patients than controls, adjusted for age,
      sex, menopause and BMI (P < 0.05 in all; effect size 0.44-0.54). Linear
      regression revealed increasing age, menopause and low BMI were independently
      associated with low BMD at the spine or hip in SSc patients. However, BMD did not
      correlate with the severity of involvement of the skin and other systems.
      CONCLUSION: BMD of the spine and hip is significantly lower in patients with SSc
      than in healthy subjects, which is independent of age, sex, menopause, low BMI
      and altered body composition.

PMID- 23006512
TI  - Overexpression of FoxM1 is associated with tumor progression in patients with
      clear cell renal cell carcinoma.
AB  - BACKGROUND: Fork head box M1 (FoxM1) is a proliferation-associated transcription
      factor essential for cell cycle progression. Numerous studies have documented
      that FoxM1 has multiple functions in tumorigenesis and its elevated levels are
      frequently associated with cancer progression. The present study was conducted to
      investigate the expression of FoxM1 and its prognostic significance in clear cell
      renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was
      further investigated in cell culture models. METHODS: Real-time quantitative PCR,
      western blot and immunohistochemistry were used to explore FoxM1 expression in
      ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was
      knocked down by small interfering RNA (siRNA) in Caki-1 and 786-O cells;
      proliferation, colony formation, cell cycle, migration, invasion, and
      angiogenesis were assayed. RESULTS: FoxM1 expression was up-regulated in the
      majority of the ccRCC clinical tissue specimens at both mRNA and protein levels.
      Clinic pathological analysis showed that FoxM1 expression was significantly
      correlated with primary tumor stage (P <0.001), lymph node metastasis (P = 0.01),
      distant metastasis (P = 0.01), TNM stage (P < 0.001) and histological grade (P =
      0.003). The Kaplan-Meier survival curves revealed that high FoxM1 expression was
      associated with poor prognosis in ccRCC patients (P < 0.001). FoxM1 expression
      was an independent prognostic marker of overall ccRCC patient survival in a
      multivariate analysis (P = 0.008). Experimentally, we found that down-regulation
      of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced
      expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and
      p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix
      metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF),
      resulting in the inhibition of migration, invasion, and angiogenesis.
      CONCLUSIONS: These results suggest that FoxM1 expression is likely to play
      important roles in ccRCC development and progression, and that FoxM1 is a
      prognostic biomarker and a promising therapeutic target for ccRCC.

PMID- 23006513
TI  - Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to
      camptothecin-like topoisomerase I inhibitors.
AB  - Topoisomerase I (TOP1) inhibitors applied in cancer therapy such as topotecan and
      irinotecan are derivatives of the natural alkaloid camptothecin (CPT). The
      mechanism of CPT poisoning of TOP1 rests on inhibition of the re-ligation
      function of the enzyme resulting in the stabilization of the TOP1-cleavable
      complex. In the presence of CPTs this enzyme-DNA complex impairs transcription
      and DNA replication, resulting in fork stalling and the formation of DNA double
      strand breaks (DSB) in proliferating cells. As with most chemotherapeutics,
      intrinsic and acquired drug resistance represents a hurdle that limits the
      success of CPT therapy. Preclinical data indicate that resistance to CPT-based
      drugs might be caused by factors such as (a) poor drug accumulation in the tumor,
      (b) high rate of drug efflux, (c) mutations in TOP1 leading to failure in CPT
      docking, or (d) altered signaling triggered by the drug-TOP1-DNA complex, (e)
      expression of DNA repair proteins, and (f) failure to activate cell death
      pathways. This review will focus on the issues (d-f). We discuss degradation of
      TOP1 as part of the repair pathway in the processing of TOP1 associated DNA
      damage, give a summary of proteins involved in repair of CPT-induced replication
      mediated DSB, and highlight the role of p53 and inhibitors of apoptosis proteins
      (IAPs), particularly XIAP and survivin, in cancer cell resistance to CPT-like
      chemotherapeutics.

PMID- 23006514
TI  - Essential roles of heparin-binding epidermal growth factor-like growth factor in
      the brain.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member
      of the EGF family of growth factors, which interacts with the EGF receptor to
      exert mitogenic activity for various types of cells. Through its interactions
      with various molecules, it is involved in diverse biological processes, including
      wound healing, blast implantation, and tumor formation. At the same time, HB-EGF
      is widely expressed in the central nervous system, including the hippocampus and
      cerebral cortex, and is considered to play pivotal roles in the developing and
      adult nervous system. Because HB-EGF protein levels in the brain are much higher
      than those of TGF-alpha and EGF, it is possible that HB-EGF serves as a major
      physiologic ligand for the EGF receptor (ErbB1) within the central nervous
      system. Recent studies indicate that HB-EGF contributes to the neuronal survival
      and proliferation of glial/stem cells. HB-EGF also promotes the survival of
      dopaminergic neurons, an action mediated by mitogen-activated protein kinase
      (MAPK) as well as by the Akt signaling pathway. In this review, we discuss recent
      findings on the implications of HB-EGF in higher brain functions of the central
      nervous system.

PMID- 23006515
TI  - Fucoidan protects against lipopolysaccharide-induced rat neuronal damage and
      inhibits the production of proinflammatory mediators in primary microglia.
AB  - BACKGROUND: Fucoidan, a sulfated polysaccharide extracted from brown algae,
      possesses potent antiinflammatory effects. AIMS: To examine the effect of
      fucoidan treatment on inflammation-mediated dopaminergic neuronal damage and its
      potential mechanisms. METHODS: Microglial activation and injury of dopaminergic
      neurons were induced by intranigral injection of lipopolysaccharide (LPS), and
      the effects of fucoidan treatment on animal behavior, microglial activation and
      survival ratio of dopaminergic neurons were investigated. We further observed the
      efficacy of fucoidan on tumor necrosis factor-alpha (TNF-alpha) and the
      production of reactive oxygen species (ROS) in LPS-activated primary microglia.
      RESULTS: Fucoidan significantly improved the behavioral manifestation, prevented
      the loss of dopaminergic neurons and inhibited the deleterious activation of
      microglia in the substantia nigra pars compacta of LPS-treated rats. Further in
      vitro experiments indicated that the excessive production of TNF-alpha and ROS in
      LPS-induced primary microglia were significantly inhibited by fucoidan
      administration. CONCLUSION: This is the first study to demonstrate that fucoidan
      possesses neuroprotective effects on injured dopaminergic neurons in a LPS
      induced animal model of Parkinson's disease. The mechanisms underlying these
      effects may include its potent down-regulation of intracellular ROS and
      subsequent proinflammatory cytokine release in LPS-activated microglia.

PMID- 23006516
TI  - Severe hypothermia in Parkinson's disease.

PMID- 23006517
TI  - The impact of obstructive sleep apnea on aortic disease in Marfan's syndrome.
AB  - BACKGROUND: Aortic dissection is a life-threatening manifestation of Marfan's
      syndrome. Preliminary evidence suggests that obstructive sleep apnea (OSA) is
      associated with aortic disease in Marfan's syndrome. OBJECTIVES: To study the
      effect of OSA on aortic events in Marfan's syndrome. METHODS: In patients with
      Marfan's syndrome, a sleep study was performed at baseline and OSA was defined as
      >5 events of apnea/hypopnea (A+H) per hour in bed. Operation because of
      progressive aortic dilatation and death because of aortic rupture were defined as
      'aortic events'. Kaplan-Meier survival analyses were used to compare event-free
      survival in patients with and without OSA. Cox regression models were used to
      explore the effects of covariates on event-free survival. RESULTS: Data from 44
      patients (mean age 37.4 years, 30 females) were available for analysis; 15
      patients (34.1%) had OSA. The median follow-up time was 29 (interquartile range
      24-36) months. Five patients had an aortic event within the follow-up time.
      Median event-free survival was 51.6 months. Event-free survival was significantly
      shorter in patients with OSA compared to patients without OSA (p = 0.012). In
      univariate analysis, A+H was associated with aortic events [hazard ratio (HR)
      1.09, 95% confidence interval (CI) 1.01-1.18, p = 0.023]. Taking the interaction
      between BMI and A+H into account increased the HR for A+H (HR 1.75, 95% CI 1.003
      3.048, p = 0.049). This association was no longer significant when other
      covariates were forced into the multivariate analysis. CONCLUSIONS: These data
      suggest that aortic event-free survival may be shorter in patients with Marfan's
      syndrome and OSA compared to patients without OSA, but more data from well
      designed studies are needed to prove this association.

PMID- 23006519
TI  - Quantitative evaluation of the disintegration of orally rapid disintegrating
      tablets by X-ray computed tomography.
AB  - To measure the rapid disintegration of Oral Disintegrating Tablets (ODT), a new
      test (XCT) was developed using X-ray computing tomography (X-ray CT). Placebo
      ODT, rapid disintegration candy (RDC) and Gaster(r)-D-Tablets (GAS) were used as
      model samples. All these ODTs were used to measure oral disintegration time (DT)
      in distilled water at 37+/-2 degrees C by XCT. DTs were affected by the width of
      mesh screens, and degree to which the tablet holder vibrated from air bubbles. An
      in-vivo tablet disintegration test was performed for RDC using 11 volunteers. DT
      by the in-vivo method was significantly longer than that using the conventional
      tester. The experimental conditions for XCT such as the width of the mesh screen
      and degree of vibration were adjusted to be consistent with human DT values.
      Since DTs by the XCT method were almost the same as the human data, this method
      was able to quantitatively evaluate the rapid disintegration of ODT under the
      same conditions as inside the oral cavity. The DTs of four commercially available
      ODTs were comparatively evaluated by the XCT method, conventional tablet
      disintegration test and in-vivo method.

PMID- 23006518
TI  - Columnar distribution of activity dependent gabaergic depolarization in
      sensorimotor cortical neurons.
AB  - BACKGROUND: GABA, the major inhibitory neurotransmitter in CNS, has been
      demonstrated to paradoxically produce excitation even in mature brain. However
      activity-dependent form of GABA excitation in cortical neurons has not been
      observed. Here we report that after an intense electrical stimulation adult
      cortical neurons displayed a transient GABA excitation that lasted for about 30s.
      RESULTS: Whole-cell patch recordings were performed to evaluate the effects of
      briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical
      slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the
      junction between layer 6 and the underlying white matter (L6/WM stimulation).
      Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization
      in the center of the column-shaped region. However, both prior to or 30s after
      stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in
      neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed
      that GABA induced depolarization is due to an increase in [Cl-]i after
      stimulation. To reveal the spatial extent of excitatory action of GABA,
      isoguvacine, a GABAA receptors agonist, was applied right after stimulation while
      monitoring the intracellular Ca2+ concentration in pyramidal neurons. Isoguvacine
      induced an increase in [Ca2+]i in pyramidal neurons especially in the center of
      the column but not in the peripheral regions of the column. The global pattern of
      the Ca2+ signal showed a column-shaped distribution along the stimulation site.
      CONCLUSION: These results demonstrate that the well-known inhibitory transmitter
      GABA rapidly switches from hyperpolarization to depolarization upon synaptic
      activity in adult somatosensory cortical neurons.

PMID- 23006520
TI  - Signatures of Gamma1-Gamma5 mixed-mode polaritons in polarized reflectance
      spectra of ZnO.
AB  - Theoretical and experimental studies were carried out on exciton-polaritons
      excited in ZnO. Polaritons in which both Gamma(1) and Gamma(5) excitons couple to
      electromagnetic waves simultaneously are shown to exist, and their signatures are
      observed in polarized reflectance spectra measured under k is perpendicular to a
      and E is parallel to c configurations for an m-plane sample. Theoretical
      calculations reveal that the mixed-mode polaritons consist of one Gamma(1)
      transverse mode and two Gamma(5) longitudinal modes. It is also shown that the
      signatures are sensitive to the valence band ordering.

PMID- 23006521
TI  - Clinical characteristics of candidaemia in adults with haematological malignancy,
      and antimicrobial susceptibilities of the isolates at a medical centre in Taiwan,
      2001-2010.
AB  - During the period 2001-2010, a total of 154 episodes of candidaemia were noted in
      111 of 2574 patients with haematological malignancies at the National Taiwan
      University Hospital (Taipei, Taiwan). Patients with acute lymphoblastic leukaemia
      had a significantly higher rate of candidaemia than patients with other
      haematological malignancies (odds ratio=2.69; P<0.001). Candida tropicalis was
      the most common Candida species (n=51; 46%), followed by Candida albicans (n=35;
      32%), Candida parapsilosis (n=13; 12%), Candida glabrata (n=8; 7%) and Candida
      krusei (n=4; 4%). Persistent candidaemia was initially identified in 21 patients
      (18.9%) and was frequently associated with central venous catheter-related
      infection (52% vs. 24%; P=0.017). Multivariate analysis revealed that shock
      (P<0.001), allogeneic transplantation (P=0.033) and elderly age (>=60 years)
      (P=0.041) were independent prognostic factors of 30-day overall survival in
      patients with haematological malignancy and candidaemia. Minimum inhibitory
      concentrations (MICs) of a total of 103 non-duplicate blood isolates of Candida
      spp., including 82 isolates from 82 patients without persistent candidaemia and
      21 isolates causing first episodes among 21 patients with persistent candidaemia,
      to nine antifungal agents were determined using the broth microdilution method.
      Among the 103 Candida isolates, 53 (51.5%), 94 (91.3%) and 102 (99.0%) were
      susceptible to itraconazole, fluconazole and voriconazole, respectively. All
      Candida isolates were susceptible to caspofungin, and 2 (15%) of the 13 C.
      parapsilosis isolates were not susceptible to micafungin or anidulafungin. The
      MIC(90) (MIC for 90% of the organisms) of posaconazole was 0.03 mg/L for C.
      albicans, 0.5 mg/L for C. tropicalis, 0.12 mg/L for C. parapsilosis and 2 mg/L
      for C. glabrata.

PMID- 23006522
TI  - Cost-effectiveness of computed tomography colonography in colorectal cancer
      screening: a systematic review.
AB  - OBJECTIVES: The European Code Against Cancer recommends individuals aged >= 50
      should participate in colorectal cancer screening. CT-colonography (CTC) is one
      of several screening tests available. We systematically reviewed evidence on, and
      identified key factors influencing, cost-effectiveness of CTC screening. METHODS:
      PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or
      cost-utility analyses of CTC-based screening, published in English, January 1999
      to July 2010. Data was abstracted on setting, model type and horizon, screening
      scenario(s), comparator(s), participants, uptake, CTC performance and cost,
      effectiveness, ICERs, and whether extra-colonic findings and medical
      complications were considered. RESULTS: Sixteen studies were identified from the
      United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom
      (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were
      used. Eleven considered direct medical costs only; five included indirect costs.
      Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy
      based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4).
      Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1).
      Three considered extra-colonic findings; seven considered complications. CTC
      appeared cost-effective versus no screening and, in general, flexible
      sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to
      colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs,
      screening uptake, threshold for polyp referral, and extra-colonic findings.
      CONCLUSION: Evidence on cost-effectiveness of CTC screening is heterogeneous, due
      largely to between-study differences in comparators and parameter values. Future
      studies should: compare CTC with currently favored tests, especially fecal
      immunochemical tests; consider extra-colonic findings; and conduct comprehensive
      sensitivity analyses.

PMID- 23006523
TI  - Assessment of the impact of rivaroxaban on coagulation assays: laboratory
      recommendations for the monitoring of rivaroxaban and review of the literature.
AB  - INTRODUCTION: Rivaroxaban does not require monitoring nor frequent dose
      adjustment. However, searching for the optimal dose in the individual patient may
      be useful in some situations. AIM: To determine which coagulation assay could be
      used to assess the impact of rivaroxaban on haemostasis and provide guidelines
      for the interpretation of routine lab tests. MATERIALS: Rivaroxaban was spiked at
      concentrations ranging from 11 to 1,090 ng/mL in plateletpoor plasma. A large
      panel of coagulation assays was tested. RESULTS: A concentration dependent
      prolongation of aPTT, PT, dPT, PiCT was observed. PT and dPT were the most
      sensitive chronometric assays but results varied depending on the reagent
      (Triniclot PT Excel S>Recombiplastin 2G>Neoplastin R>Neoplastin CI+>Triniclot PT
      Excel>Triniclot PT HTF>Innovin). FXa chromogenic assays showed the highest
      sensitivity. In TGA, Cmax was the most sensitive parameter with the tissue factor
      induced pathway. Rivaroxaban interferes on haemostasis diagnostic tests such the
      measurement of clotting factors, fibrinogen, antithrombin, proteins C and S,
      activated protein-C resistance and Xa-based chomogenic assays. CONCLUSIONS: PT
      may be used as screening test to assess the risk of bleedings. A more specific
      and sensitive assay such as Biophen DiXaI using calibrators should be used to
      confirm the concentration of rivaroxaban. We also propose cut-off associated with
      a bleeding or thrombosis risk based on pharmacokinetic studies. Standardization
      of the time between the last intake of rivaroxaban and the sampling is mandatory.

PMID- 23006526
TI  - Relevance of prehospital stroke code activation for acute treatment measures in
      stroke care: a review.
AB  - BACKGROUND: The use of emergency services with prehospital stroke assessment and
      early notification to the treatment hospital (stroke code) is a crucial
      determinant of delay time for acute stroke treatment. We reviewed and summarized
      the literature on prehospital stroke code system implementation. METHODS: Two
      databases were explored (last update June 20, 2011) with 3 key words (stroke
      code, stroke prehospital management and stroke prehospital services). Inclusion
      criteria were: randomized and quasirandomized controlled trials, cohort and case
      control studies, and hospital- and emergency-based registers, with no year or
      language restrictions. We examined the reference lists of all included articles.
      All potentially relevant reports and abstracts were transcribed into a
      specifically designed data abstraction form. RESULTS: Only 19 of the 680 studies
      which were initially retrieved, published from 1999 to 2011, fulfilled our
      inclusion criteria. One clinical trial was identified. Large differences in
      stroke code procedures and study designs within and across countries prohibited
      the pooling of the data. Most studies were carried out in urban areas. Assuming
      the rate of tissue-plasminogen activator treatment as the performance measure,
      most studies report a significant increase in the rate of treatment (increase
      between 3.2 and 16%) with only 1 study not reporting any increase. CONCLUSIONS:
      Despite its limitations, this review suggests that the use of prehospital stroke
      code is an important intervention to improve the accessibility of the benefits of
      thrombolysis, especially when implemented together with educational campaigns to
      optimize the awareness and behavior of patients and bystanders.

PMID- 23006528
TI  - A pharmacy led program to review anti-psychotic prescribing for people with
      dementia.
AB  - BACKGROUND: Anti-psychotics, prescribed to people with dementia, are associated
      with approximately 1,800 excess annual deaths in the UK. A key public health
      objective is to limit such prescribing of anti-psychotics. METHODS: This project
      was conducted within primary care in Medway Primary Care Trust (PCT) in the UK.
      There were 2 stages for the intervention. First, primary care information systems
      including the dementia register were searched by a pharmacy technician to
      identify people with dementia prescribed anti-psychotics. Second, a trained
      specialist pharmacist conducted targeted clinical medication reviews in people
      with dementia initiated on anti-psychotics by primary care, identified by the
      data search. RESULTS: Data were collected from 59 practices. One hundred and
      sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose
      anti-psychotics. People with dementia living in residential homes were nearly 3.5
      times more likely to receive an anti-psychotic [25.5% of care home residents
      (118/462) vs. 7.3% of people living at home (43/589)] than people living in their
      own homes (p < 0.0001; Fisher's exact test). In 26 practices there was no-one on
      the dementia register receiving low-dose anti-psychotics.Of the 161 people with
      dementia prescribed low-dose anti-psychotics, 91 were receiving on-going
      treatment from local secondary care mental health services or Learning Disability
      Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or
      the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led
      medication review. CONCLUSIONS: In total 15.3% of people on the dementia register
      were receiving a low-dose anti-psychotic. However, such data, including the
      recent national audit may under-estimate the usage of anti-psychotics in people
      with dementia. Anti-psychotics were used more commonly within care home settings.
      The pharmacist-led medication review successfully limited the prescribing of anti
      psychotics to people with dementia.

PMID- 23006527
TI  - ACR appropriateness criteria(r)  resectable rectal cancer.
AB  - The management of resectable rectal cancer continues to be guided by clinical
      trials and advances in technique. Although surgical advances including total
      mesorectal excision continue to decrease rates of local recurrence, the
      management of locally advanced disease (T3-T4 or N+) benefits from a
      multimodality approach including neoadjuvant concomitant chemotherapy and
      radiation. Circumferential resection margin, which can be determined
      preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy
      is decreased by placing the patient in the prone position on a belly board,
      however for patients who cannot tolerate prone positioning, IMRT decreases the
      volume of normal tissue irradiated. The use of IMRT requires knowledge of the
      patterns of spreads and anatomy. Clinical trials demonstrate high variability in
      target delineation without specific guidance demonstrating the need for peer
      review and the use of a consensus atlas. Concomitant with radiation, fluorouracil
      based chemotherapy remains the standard, and although toxicity is decreased with
      continuous infusion fluorouracil, oral capecitabine is non-inferior to the
      continuous infusion regimen. Additional chemotherapeutic agents, including
      oxaliplatin, continue to be investigated, however currently should only be
      utilized on clinical trials as increased toxicity and no definitive benefit has
      been demonstrated in clinical trials. The ACR Appropriateness Criteria are
      evidence-based guidelines for specific clinical conditions that are reviewed
      every two years by a multidisciplinary expert panel. The guideline development
      and review include an extensive analysis of 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 those instances where evidence is lacking or not definitive,
      expert opinion may be used to recommend imaging or treatment.

PMID- 23006529
TI  - Antiphospholipid antibody profiling: time for a new technical approach?
AB  - Detection of anti-phospholipid (aPL) antibodies for state-of-the art diagnosis of
      antiphospholipid syndrome(APS) still remains a laboratory challenge due to the
      great diversity of aPL antibodies and their relevance with regard to the
      diagnostic criteria. According to the recently revised classification criteria
      for APS, several enzyme-linked immunosorbent assays (ELISAs) should be performed
      simultaneously in routine laboratories for the detection of aPL antibodies.
      Therefore, new approaches to aPL profiling have been proposed recently to provide
      information regarding diagnosis and eventually outcome in APS patients. Multiplex
      analysis could meet the increasing demand for cost-efficient detection and
      profiling of aPL antibodies. Multi-line immunodot assays or bead-based multiplex
      techniques candidate as alternatives to assess several aPL antibodies
      simultaneously employing different solid-phases for bound/free separation of
      reactants. Particularly, multi-line immunodot assays present an alternative to
      ELISA for aPL antibody detection and profiling in APS patients. The use of
      hydrophobic membranes as solid-surface by this technique appears to offer a
      distinct solid-phase reaction environment for the assessment of aPL antibodies.
      This article reviews novel developments in the field of laboratory diagnostics of
      APS with special emphasis on multiplex assays.

PMID- 23006531
TI  - Hepatitis C virus infection and related risk factors among injection drug users
      in Montenegro.
AB  - BACKGROUND: In Southeastern Europe, similar to other postsocialist regions on the
      continent, injection drug users (IDU) are exposed to a high risk of blood-borne
      infections. In this paper, we report the prevalence of HIV, hepatitis C (HCV) and
      hepatitis B (HBV) among IDUs in Montenegro. We also examine the risk factors
      associated with HCV diagnosis. METHODS: In 2008, 322 IDUs in Montenegro
      participated in a respondent-driven sampling survey. Blood specimens were
      collected and tested for HIV, HCV and HBV. Behavioral data were collected with
      self-administered questionnaires. RESULTS: In comparison to 2005, HCV prevalence
      had increased from an estimated 22 to 53.7%. Only one HIV and no HBV cases were
      detected. Anti-HCV positivity was associated with the region of origin, income,
      sharing injection equipment and frequency of injecting drugs. CONCLUSION: The
      increasing HCV prevalence among IDUs in Montenegro calls for increased and better
      designed programs to prevent its further spread and a potential HIV outbreak.

PMID- 23006530
TI  - Lipid accumulation product: a simple and accurate index for predicting metabolic
      syndrome in Taiwanese people aged 50 and over.
AB  - BACKGROUND: Lipid accumulation product (LAP) has been advocated as a simple
      clinical indicator of metabolic syndrome (MS). However, no studies have evaluated
      the accuracy of LAP in predicting MS in Taiwanese adults. The aim of our
      investigation was to use LAP to predict MS in Taiwanese adults. METHODS:
      Taiwanese adults aged 50 years and over (n = 513) were recruited from a physical
      examination center at a regional hospital in southern Taiwan. MS was defined
      according to the MS criteria for Taiwanese people. LAP was calculated as (waist
      circumference [cm] - 65) * (triglyceride concentration [mM]) for men, and (waist
      circumference [cm] - 58) * (triglyceride concentration [mM]) for women. Simple
      logistic regression and receiver-operating characteristic (ROC) analyses were
      conducted. RESULTS: The prevalence of MS was 19.5 and 21.5% for males and
      females, respectively. LAP showed the highest prediction accuracy among adiposity
      measures with an area under the ROC curve (AUC) of 0.901. This was significantly
      higher than the adiposity measure of waist-to-height ratio (AUC = 0.813).
      CONCLUSIONS: LAP was a simple and accurate predictor of MS in Taiwanese people
      aged 50 years and over. LAP had significantly higher predictability than other
      adiposity measures tested.

PMID- 23006532
TI  - Trauma nursing development in England: insight from South Africa.
AB  - National data found that patients with major trauma receive inadequate care. The
      effectiveness of regional trauma networks in improving mortality and outcomes for
      patients presenting with major trauma has been recognised and being established.
      In parallel, it is recognised that trauma training for nurses must be further
      developed. An observational study tour to South Africa trauma units, to document
      trauma practice was sponsored by the Florence Nightingale Foundation and General
      Nursing Council (GNC). Despite significant cultural and contextual differences,
      South Africa's trauma centres have a worldwide reputation in managing trauma and
      can offer valuable insights and experience. Recommendations are made which
      acknowledge the role of regional trauma networks, improved accessibility to
      formal trauma training and the use of local professional development resources in
      improving the content of and access to trauma education for nurses. A development
      programme for trauma nurses is suggested. The benefits of international learning
      are detailed and a transferable local training package for trauma training for
      nurses is explained. 

PMID- 23006533
TI  - Evaluation of school transportation patterns and the associated impact on BMI in
      2 Midwestern communities.
AB  - BACKGROUND: The decline in active commuting to and from school in the United
      States is, in part, due to urban design standards and public policies that
      promote automobile travel and discourage pedestrian activity. PURPOSE: The
      current investigation examines active commuting at neighborhood schools and how
      it is altered by distance to school, student age and its potential impact on Body
      Mass Index. METHODS: Demographic and transportation datasets were obtained for
      5367 elementary students (K-5th grade) and middle school students (6th-8th grade)
      in 2 Midwestern communities. RESULTS: 4379 (81.6%) students were successfully
      geocoded and 21.9% actively commute to school at least half of the time meeting
      the Healthy People 2010 objective 22-14. Of those students who could potentially
      actively commute to school (0.5 mile for grades K-5 and 1 mile for grades 6-8)
      36.6% are passive commuters. No significant negative associations were found
      between BMI z-score or BMI percentile with accumulation of activity through
      active commuting (frequency * distance) for elementary (r = -0.04, P = .27) or
      middle school students (r = .027, P = .56). CONCLUSION: Many elementary students
      living within 0.3-0.4 miles are being driven to school. Promoting pedestrian
      friendly communities and making healthy and sustainable transportation choices
      should be priorities for community leaders and school administrators.

PMID- 23006534
TI  - Effects of helium and air inhalation on the innate and early adaptive immune
      system in healthy volunteers ex vivo.
AB  - BACKGROUND: Helium inhalation protects myocardium, brain and endothelium against
      ischemia/reperfusion injury in animals and humans, when applied according to
      specific "conditioning" protocols. Before widespread use of this "conditioning"
      agent in clinical practice, negative side effects have to be ruled out. We
      investigated the effect of prolonged helium inhalation on the responsiveness of
      the human immune response in whole blood ex vivo. METHODS: Male healthy
      volunteers inhaled 30 minutes heliox (79%He/21%O(2)) or air in a cross over
      design, with two weeks between measurements. Blood was withdrawn at T0
      (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and
      incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli
      anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not
      incubated (0 h). An additional group of six volunteers inhaled 60 minutes of
      heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6),
      interleukin-8 (IL-8), interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) was
      analyzed by cytometric bead array. Statistical analysis was performed by the
      Wilcoxon test for matched samples. RESULTS: Incubation with LPS, LTA or TCS
      significantly increased TNF-alpha, IL-1beta, IL-6, IL-8, IFN-gamma and IL-2 in
      comparison to incubation with RPMI alone. Thirty min of helium inhalation did not
      influence the amounts of TNF-alpha, IL-1beta, IL-6, IL-8, IFN-gamma and IL-2 in
      comparison to air. Sixty min of helium inhalation did not affect cytokine
      production after LPS stimulation. CONCLUSIONS: We conclude that 79% helium
      inhalation does not affect the responsiveness of the human immune system in
      healthy volunteers. TRIAL REGISTRATION: Dutch Trial Register:
      http://www.trialregister.nl/ NTR2152.

PMID- 23006535
TI  - N-acetylcysteine downregulation of lysyl oxidase activity alleviating bleomycin
      induced pulmonary fibrosis in rats.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung
      disease without beneficial therapy, except for lung transplantation. A high oral
      dose of N-acetylcysteine (NAC) added to prednisone and azathioprine has been
      found to improve lung function in IPF patients, though the mechanism of action
      remains poorly understood. OBJECTIVE: Based on our previous findings showing
      elevation of glutathione (GSH) content associated with downregulation of lysyl
      oxidase (LOX) activity, which is essential for collagen deposition, the aim of
      the present study was to test the hypothesis that NAC alleviates IPF by
      regulating LOX function. METHODS: We firstly analyzed the time course of collagen
      deposition in lung tissue, hydroxyproline content, LOX activity, GSH levels, and
      transforming growth factor-beta(1) (TGF-beta(1)) and alpha-smooth muscle actin
      (alpha-SMA) expression in bleomycin (BLM)-induced pulmonary fibrosis in a rat
      model. Then, we focused our studies on NAC modulation of LOX activity. RESULTS:
      LOX activity was increased on day 9 and peaked 14 days after BLM administration,
      while TGF-beta(1) protein peaked on day 9. Interestingly, NAC treatment for 14
      days from day 0 reversed LOX activity to normal levels and increased GSH levels
      in the lung of BLM-dosed rats. Consistently, NAC partially attenuated pulmonary
      fibrosis and inhibited TGF-beta(1) and alpha-SMA expression in this model.
      CONCLUSIONS: Our study supports a novel mechanism of NAC alleviating IPF by
      inhibition of LOX activity via elevation of lung GSH in BLM-induced pulmonary
      fibrosis. The TGF-beta(1)/alpha-SMA pathway may also play an important role in
      modulation of LOX activity.

PMID- 23006536
TI  - The effect of hybridization on local magnetic interactions at highly diluted Ce
      ions in tetragonal intermetallic compounds RERh2Si2 (RE=Ce, Pr, Nd, Gd, Tb, Dy).
AB  - The contribution of the 4f electron to the local magnetic field at highly diluted
      Ce atoms in RERh(2)Si(2) (RE = Ce, Pr, Nd, Gd, Tb, Dy) has been investigated as a
      function of temperature through the measurement of the magnetic hyperfine field
      in (140)Ce nuclei by time differential perturbed gamma-gamma angular correlation
      spectroscopy. Samples of the studied compounds were characterized by x-ray
      diffraction and zero-field resistance to determine the crystal structure and
      transport properties. DC magnetic susceptibility was measured for NdRh(2)Si(2).
      It was observed that the variation of the magnetic hyperfine field with
      temperature follows the expected behaviour for the host magnetization, with the
      exception of GdRh(2)Si(2), which showed a strong deviation from such a behaviour.
      It is shown that the hybridization of the d band of the host with the f band of
      the Ce impurity, which is stronger in GdRh(2)Si(2) than in other compounds, is
      responsible for the observed deviation from the expected temperature dependence
      of the hyperfine field. The origin of this stronger hybridization is ascribed to
      the relatively small magnetic anisotropy observed in GdRh(2)Si(2) when compared
      with the other compounds of the series, as shown by resistance measurements.

PMID- 23006537
TI  - In vitro cytokine profiles and viability of different human cells treated with
      whole cell lysate of Mycobacterium avium subsp. paratuberculosis.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) is a zoonotic pathogen, a very
      slow growing bacterium which is difficult to isolate and passage in conventional
      laboratory culture. Although its association with Johne's disease or
      paratuberculosis of cattle is well established, it has been only putatively
      linked to Crohn's disease in humans. Further, MAP has been recently suggested to
      be a trigger for other autoimmune diseases such as type-1 diabetes mellitus
      (T1DM). Recently, some studies have indicated that exposure to MAP is associated
      with elevated levels of antibodies against MAP lysate although the exact
      mechanism and significance of the same remains unclear. Further, the cytokine
      profiles relevant in MAP associated diseases of humans and their exact role in
      the pathophysiology are not clearly known. We performed in vitro cytokine
      analyses after exposing different cultured human cells to the whole cell lysate
      of MAP and found that MAP lysate induces secretion of cytokines IL-1beta, IL-6,
      IL-8, IL-10 and TNF-alpha by human peripheral blood mononuclear cells (PBMCs).
      Also, it induces secretion of IL-8 by cultured human stomach adenocarcinoma cells
      (AGS) and PANC-1(human pancreatic carcinoma cell line) cells. We also found that
      MAP lysate induced cytotoxicity in PANC-1cells. Collectively, these results
      provide a much needed base-line data set of cytokines broadly signifying a MAP
      induced cellular response by human cells.

PMID- 23006538
TI  - A nanostructured liquid crystalline formulation of 20(S)-protopanaxadiol with
      improved oral absorption.
AB  - As with many other anti-cancer agents, 20(S)-protopanaxadiol (PPD) has a low oral
      absorption. In this study, in order to improve the oral bioavailability of PPD,
      the cubic nanoparticles that it contains were used to enhance absorption.
      Therefore, the cubic nanoparticle loaded PPD were prepared through the
      fragmentation of the glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and
      were verified by transmission electron microscope, small angle X-ray scattering
      and differential scanning calorimetry. The in vitro release of 20(S)
      protopanaxadiol from these nanoparticles was less than 5% at 12h. And then Caco-2
      cell monolayer model was used to evaluate the absorption of PPD in vitro.
      Meanwhile the rat intestinal perfusion model and bioavailability were also
      estimated in vivo. The results showed that, in the Caco-2 cell model, the PPD
      cubosome could increase the permeability values from the apical (AP) to the
      basolateral (BL) of PPD at 53%. The result showed that the four-site rat
      intestinal perfusion model was consistent with the Caco-2 cell model. And the
      result of a pharmacokinetic study in rats showed that the relative
      bioavailability of the PPD-cubosome (AUC(0-infinity)) compared with the raw PPD
      (AUC(0-infinity)) was 169%. All the results showed that the PPD-cubosome enhanced
      bioavailability was likely due to the increased absorption by the cubic
      nanoparticles rather than by the improved release. Hence, the cubic nanoparticles
      may be a promising oral carrier for the drugs that have a poor oral absorption.

PMID- 23006539
TI  - Low molecular weight fucoidan from the sporophyll of Undaria pinnatifida
      suppresses inflammation by promoting the inhibition of mitogen-activated protein
      kinases and oxidative stress in RAW264.7 cells.
AB  - The suppression of MAPK and oxidative stress could be an important anti
      inflammatory mechanism. Fucoidan regulates MAPK activity in several cell lines.
      However, the mechanism for the anti-inflammatory and oxidative stress effect of
      low molecular weight fucoidan (LMWF) is poorly understood in RAW264.7 cells. The
      objective of this study was to examine the critical role of LMWF during LPS
      induced inflammation in RAW264.7 cells. To determine the potential role of LMWF,
      we analysed pro-inflammatory cytokine, transcription factor, inflammation-related
      and oxidative stress related protein expression in vitro during LPS-induced
      inflammation in RAW264.7 cells. In this study, we demonstrated the anti
      inflammatory effects of LMWF on LPS-induced inflammation in macrophages through
      the regulation of signalling pathways, including its effect on the attenuation of
      inflammatory cytokines, such as IL-1beta, IL-1 and TNF-alpha, and the degradation
      of phosphorylated p38 MAPK, ERK1/2 and JNK. This study also demonstrates that
      LMWF might block NO as well as the expression of reactive oxygen species (ROS),
      which subsequently inhibits the iNOS and COX-2 expression induced by LPS. Based
      on these findings, we suggest that LMWF might have great potential as an external
      pathogen prevention and intervention agent for inflammatory diseases.

PMID- 23006540
TI  - Cost-utility analysis of liraglutide versus glimepiride as add-on to metformin in
      type 2 diabetes patients in China.
AB  - OBJECTIVES: The aim of this study was to evaluate the long-term cost-utility of
      liraglutide versus glimepiride as add-on therapy to metformin in patients with
      type 2 diabetes mellitus (T2DM), based on the results of clinical trial conducted
      in Asian population. METHODS: The validated UKPDS Outcomes Model was used to
      project life expectancy, quality adjusted life-years (QALYs), incidence of
      diabetes-related complication and cost of complications in patients receiving
      those regimens. Baseline cohort characteristics and treatment effects were
      derived from an Asian study. China-specific complication costs and utility score
      were taken from local studies. Patients' outcomes were modeled for 30 years and
      incremental cost-effectiveness ratios were calculated for liraglutide compared
      with glimepiride from the healthcare system perspective. Both future costs and
      clinical benefits were discounted at 3 percent. Sensitivity analyses were
      performed. RESULTS: Over a period of 30 years, compared with glimepiride,
      liraglutide 1.8 mg was associated with improvements in life expectancy (0.1 year)
      and quality adjusted life-year (0.168 QALY), and a reduced incidence of diabetes
      related complications leading to an incremental cost-effectiveness ratio per QALY
      gained versus glimepiride of CNY 25,6871 (DEC 2010, 1 USD = 6.6227 CNY).
      CONCLUSIONS: Long-term projections indicated that liraglutide was associated with
      increased life expectancy, QALYs, and reduced complication incidences comparing
      with glimepiride. When the UK cost of liraglutide was discounted by 38 percent,
      liraglutide would be a cost-effective option in China from the healthcare system
      perspective using the 3X GDP/capita per QALY as the WTP threshold.

PMID- 23006541
TI  - Influenza virus infects bone marrow mesenchymal stromal cells in vitro:
      implications for bone marrow transplantation.
AB  - Mesenchymal stromal cells (MSCs) have differentiation, immunomodulatory, and self
      renewal properties and are, therefore, an attractive tool for regenerative
      medicine and autoimmune diseases. MSCs may be of great value to treat graft
      versus-host disease. Influenza virus causes highly contagious seasonal infection
      and occasional pandemics. The infection is severe in children, elderly, and
      immunocompromised hosts including hematopoietic stem cell transplant patients.
      The objective of this study was to determine if MSCs are permissive to influenza
      virus replication. We isolated MSCs from the bone marrow of 4- to 6-week-old germ
      free pigs. Swine and human influenza virus strains were used to infect MSCs in
      vitro. MSCs expressed known influenza virus alpha-2,3 and alpha-2,6 sialic acid
      receptors and supported replication of swine and human influenza viruses. Viral
      infection of MSCs resulted in cell lysis and proinflammatory cytokine production.
      These findings demonstrate that bone marrow-derived MSCs are susceptible to
      influenza virus. The data also suggest that transplantation of bone marrow MSCs
      from influenza virus-infected donors may transmit infection to recipients. Also,
      MSCs may get infected if infused into a patient with an ongoing influenza virus
      infection.

PMID- 23006542
TI  - Dietary supplementation of high-performance Korean and Japanese judoists.
AB  - This research investigated patterns of the use of dietary supplement and doping
      awareness among high-ranked judoists from 2 countries. Korean (70 men and 31
      women) and Japanese (37 men and 34 women) national judo team members were divided
      into 2 groups (high and low competitive performance levels) according to their
      international and national rankings. Fifty-nine percent of Korean and 61% of
      Japanese judoists consumed dietary supplements. Eighty-eight percent of high- and
      51% of low-competitive-performance-level Korean judoists consumed dietary
      supplements. Sixty-eight percent of high- and 57% of low-competitive-performance
      level Japanese judoists consumed dietary supplements. Oriental supplements (34%),
      vitamins (23%), and protein powder (12%) were the most commonly consumed dietary
      supplements in Korean judoists. Vitamins (45%), protein powder (33%), and
      minerals (15%) were the most commonly consumed dietary supplements in Japanese
      judoists. Thirty-eight percent of judoists from both countries had not received
      any proper education about antidoping, and 44% of judoists from both countries
      had not received knowledge of antidoping legislation. There was a significant
      difference in education about antidoping between high and low competitive
      performance levels of Korean judoists (p < .001). Korean judoists received
      significantly less antidoping education than Japanese judoists (p < .001). The
      associations for antidoping education and knowledge of antidoping legislation
      with the use of dietary supplements were 3.46 (95% CI = 1.31-9.12) and 1.63 (95%
      CI = 0.71-3.76), respectively. Our findings showed that use of dietary
      supplements in judoists from both countries was increased after experiencing
      antidoping education.

PMID- 23006543
TI  - Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is
      linked to dysregulated monocyte IL-1beta production.
AB  - BACKGROUND: The exact pathogenesis of the pediatric disorder periodic fever,
      aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown.
      OBJECTIVES: We hypothesized that PFAPA might be due to dysregulated monocyte IL
      1beta production linked to genetic variants in proinflammatory genes. METHODS:
      Fifteen patients with PFAPA syndrome were studied during and outside a febrile
      episode. Hematologic profile, inflammatory markers, and cytokine levels were
      measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to
      secrete IL-1beta was assessed by using ELISA, and active IL-1beta secretion was
      visualized by means of Western blotting. Real-time quantitative PCR was performed
      to assess cytokine gene expression. DNA was screened for variants of the MEFV,
      TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome.
      RESULTS: During a febrile attack, patients with PFAPA syndrome revealed
      significantly increased neutrophil counts, erythrocyte sedimentation rates, and C
      reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12
      levels compared with those seen outside attacks. Stimulated PBMCs secreted
      significantly more IL-1beta during an attack (during a febrile episode, 575 +/-
      88 pg/mL; outside a febrile episode, 235 +/- 56 pg/mL; P < .001), and this was in
      the mature active p17 form. IL-1beta secretion was inhibited by ZYVAD, a caspase
      inhibitor. Similar results were found for stimulated monocytes (during a febrile
      episode, 743 +/- 183 pg/mL; outside a febrile episode, 227 +/- 92 pg/mL; P <
      .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3
      variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant. CONCLUSION: Our
      data strongly suggest that IL-1beta monocyte production is dysregulated in
      patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3
      variants, suggesting that inflammasome-related genes might be involved in this
      autoinflammatory syndrome.

PMID- 23006544
TI  - Spiking venom with rVes v 5 improves sensitivity of IgE detection in patients
      with allergy to Vespula venom.

PMID- 23006545
TI  - IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and
      peanut allergic sensitization.
AB  - BACKGROUND: Allergen exposure at lung and gut mucosae can lead to aberrant T(H)2
      immunity and allergic disease. The epithelium-associated cytokines thymic stromal
      lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the
      initiation of these responses. OBJECTIVE: We sought to investigate the
      contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to
      the common allergens house dust mite (HDM) or peanut. METHODS: Neutralizing
      antibodies or mice deficient in TSLP, IL-25, or IL-33 signaling were exposed to
      HDM intranasally or peanut intragastrically, and immune inflammatory and
      physiologic responses were evaluated. In vitro assays were performed to examine
      specific dendritic cell (DC) functions. RESULTS: We showed that experimental HDM
      induced allergic asthma and food allergy and anaphylaxis to peanut were
      associated with TSLP production but developed independently of TSLP, likely
      because these allergens functionally mimicked TSLP inhibition of IL-12 production
      and induction of OX40 ligand (OX40L) on DCs. Blockade of OX40L significantly
      lessened allergic responses to HDM or peanut. Although IL-25 and IL-33 induced
      OX40L on DCs in vitro, only IL-33 signaling was necessary for intact allergic
      immunity, likely because of its superior ability to induce DC OX40L and expand
      innate lymphoid cells in vivo. CONCLUSION: These data identify a nonredundant, IL
      33-driven mechanism initiating T(H)2 responses to the clinically relevant
      allergens HDM and peanut. Our findings, along with those in infectious and
      transgenic/surrogate allergen systems, favor a paradigm whereby multiple
      molecular pathways can initiate T(H)2 immunity, which has implications for the
      conceptualization and manipulation of these responses in health and disease.

PMID- 23006546
TI  - Dysregulated synthesis of protectin D1 in eosinophils from patients with severe
      asthma.
AB  - BACKGROUND: Protectin D1 (PD1) is an anti-inflammatory and proresolving lipid
      mediator biosynthesized from the omega-3 fatty acid docosahexaenoic acid (DHA).
      Exogenous PD1 conferred protection against eosinophilic inflammation in animals
      with experimental asthma, although its endogenous cellular source and functions
      in human airways are of interest. OBJECTIVE: We sought to investigate the
      synthesizing capacity of PD1 in eosinophils from healthy subjects and patients
      with severe asthma and its direct effects on eosinophil functions. METHODS: Human
      eosinophil-derived metabolites of arachidonic acid and DHA were analyzed with
      liquid chromatography-tandem mass spectrometry-based lipidomic analysis. The
      biological activities of PD1 on the function of human eosinophils, including
      chemotaxis, adhesion molecule expressions, degranulation, superoxide anion
      generation, or survival, were examined. RESULTS: We identified PD1 as one of the
      main anti-inflammatory and proresolving molecules synthesized in human
      eosinophils. PD1, in nanomolar concentrations, suppressed the chemotaxis induced
      by CCL11/eotaxin-1 or 5-oxo-eicosatetraenoic acid and modulated the expression of
      the adhesion molecules CD11b and L-selectin, although it had no effects on the
      degranulation, superoxide anion generation, or survival of the eosinophils.
      Compared with the cells harvested from healthy subjects, we observed a prominent
      decrease in the biosynthesis of PD1 by eosinophils from patients with severe
      asthma, even in presence of DHA. CONCLUSION: These observations are a first
      indication that activated human eosinophils represent a major source of PD1,
      which can act as a self-resolving machinery in eosinophilic inflammation, whereas
      the production of PD1 is impaired in patients with severe asthma.

PMID- 23006547
TI  - Future directions in family and professional caregiving for the elderly.
AB  - As the population ages and the expected wave of baby boomers settles into old
      age, there is a pressing need to examine the people and institutions that care
      for elders and the ways in which the system will need to adapt during the next 5
      10 years to accommodate the needs of the elderly and of their caregivers. This
      paper examines future directions in this field, identifying the major issues from
      two perspectives: family caregiving and professional caregiving. Despite
      extensive research on caregiving, more attention to a series of methodological
      issues is needed, as is more extensive evaluation of promising intervention
      models in community and institutional settings. Effective strategies to lower
      caregiver distress and improve the quality of care can be implemented in
      efficient ways that manage costs, but the argument for innovations must be made
      based on efficacy.

PMID- 23006549
TI  - Extensive white matter changes predict stroke recurrence up to 5 years after a
      first-ever ischemic stroke.
AB  - BACKGROUND: White matter changes (WMCs), a surrogate for small-vessel disease
      (SVD), have been shown to be associated with a major negative influence on
      cognition, mood and functioning in daily life. We aimed to investigate whether
      severe WMCs are a risk factor for recurrent ischemic stroke in a long-term follow
      up. METHODS: 320 consecutive patients admitted to hospital with a first-ever
      ischemic stroke were included in the study and followed up for 12 years using
      extensive national registers. Patients were aged between 55 and 85 years, with a
      mean age of 70.8 years. WMCs were rated using MRI and stratified into two grades:
      absent to moderate WMCs versus severe WMCs. Univariate analysis was performed
      using binary logistic regression analysis, Kaplan-Meier log rank analysis and
      life table function. To control for factors such as age, education and
      cardiovascular risk factors, a multivariate Cox regression proportional hazards
      analysis was made with forced entry. RESULTS: At least one recurrent stroke,
      nonfatal or fatal, was diagnosed in 76 (23.8%) patients at 5 years and in 127
      (39.7%) patients at 12 years. In univariate analysis, only advancing age was
      associated with WMCs. The cumulative 5-year recurrence risk was 24.5% [95%
      confidence interval (95% CI) 23.8-25.2] for patients with absent to moderate WMCs
      and 39.1% (95% CI 38.1-40.1) for patients with severe WMCs. The cumulative 12
      year recurrence risk was 48.1% (95% CI 45.5-50.7) for patients with absent to
      moderate WMCs and 60.9% (95% CI 56.7-65.1) for patients with severe WMCs. In Cox
      regression proportional hazards analysis, independent predictors of recurrent
      stroke at 5 years were severe WMCs [hazard ratio (HR) 1.80, 95% CI 1.11-2.95],
      atrial fibrillation (HR 1.81, 95% CI 1.09-3.02), hypertension (HR 1.69, 95% CI
      1.05-2.71) and peripheral arterial disease (HR 1.89, 95% CI 1.06-3.38). At 12
      years, only increasing age remained as an independent predictor (HR 1.04, 95% CI
      1.02-1.07). In receiver operating characteristic analysis, the area under the
      curve for severe WMCs was 0.58 (95% CI 0.51-0.65) for the prediction of stroke
      recurrence within 5 years. CONCLUSIONS: In our well-defined cohort of poststroke
      patients, the presence of severe WMCs was an indicator of stroke recurrence up to
      5 years after a first-ever ischemic stroke. WMCs can be considered as an SVD
      marker that summarizes the effects of several classical risk factors on the small
      vessel brain network and therefore can be used as a score for risk stratification
      of stroke recurrence. Our findings further underline the poor long-term prognosis
      of cerebral SVD.

PMID- 23006548
TI  - Wound healing after radiation therapy: review of the literature.
AB  - Radiation therapy is an established modality in the treatment of head and neck
      cancer patients. Compromised wound healing in irradiated tissues is a common and
      challenging clinical problem. The pathophysiology and underlying cellular
      mechanisms including the complex interaction of cytokines and growth factors are
      still not understood completely. In this review, the current state of research
      regarding the pathomechanisms of compromised wound healing in irradiated tissues
      is presented. Current and possible future treatment strategies are critically
      reviewed.

PMID- 23006550
TI  - Simple pretreatment of non-conductive small hydrous bio-samples with choline-type
      ionic liquid and membrane filter for microsample mounting.
AB  - Choline-type ionic liquids (CILs), which have a molecular structure resembling
      that of the vitamin-like active substance choline, have high water solubility,
      high osmotic pressure, and high cell membrane permeability. Their physical
      properties make them a very useful pretreatment agent for scanning electron
      microscopy (SEM) observation of hydrous samples because they can replace water in
      the samples, causing them to retain their shapes. SEM images of pollen without
      dissolution of cell membranes, damage, or deformation were obtained by a simple
      visualization process using CILs. We also identified an easy pretreatment
      protocol for SEM observation of hydrous microsamples that uses a membrane filter
      as a sample stage to ensure correct sample placement. Bacteria were successfully
      observed by using this protocol.

PMID- 23006551
TI  - Synthesis of silver nanoparticles by polysaccharide bioflocculant produced from
      marine Bacillus subtilis MSBN17.
AB  - The polysaccharides are emerging as stabilizing and reducing agents for
      nanoparticles synthesis, however the commercial polysaccharides are not
      economically viable. Therefore, the exopolysaccharide from microbial origin such
      as bioflocculants are promising alternate for the synthesis and stabilization of
      nanoparticles. In this report, a bioflocculant (MSBF17) was produced from marine
      sponge-associated Bacillus subtilis MSBN17 under submerged fermentation using the
      economical substrates. The production was statistically optimized with most
      significant factors such as palm jaggery, NH(4)NO(2), K(2)HPO(4) and NaCl. The
      maximum bioflocculant production obtained with statistically optimized medium was
      13.42 g/l. Based on the biochemical composition and FT-IR analysis, the
      flocculant compound was predicted as a polysaccharide derivative. The
      flocculating activity of the MSBF17 was invariably considerable at high salinity
      and temperature. It was found that the nano-scale silver can be synthesized in
      reverse micelles using the bioflocculant as stabilizer. The silver nanoparticles
      (AgNPs) were characterized by UV-spectroscopy, FT-IR and TEM analysis. The AgNPs
      were spherical shaped (60 nm) and stable for 5 months. Therefore, the
      bioflocculant-mediated synthesis of nanomaterials can be considered as
      environmental benign greener approach.

PMID- 23006552
TI  - Covalent bonding of GYIGSR to EVAL membrane surface to improve migration and
      adhesion of cultured neural stem/precursor cells.
AB  - In the present study, we modified poly (ethylene-co-vinyl alcohol) (EVAL)
      membranes with the covalent bonding of the laminin-derived peptides, GYIGSR by
      using carbodiimidazole (CDI) to activate the hydroxyl groups on the membrane
      surface. The resulting GYIGSR-immobilized EVAL (EVAL-GYIGSR) membrane was
      analyzed in terms of the effect of immobilized peptide sequence on the behaviors
      of neural stem/precursor cells (NSPCs), isolated from embryonic rat cerebral
      cortex, in the serum-free medium. Compared to the unmodified EVAL, GYIGSR
      immobilized on the EVAL membrane was shown to significantly increase NSPCs
      migrating out of neurospheres (p<0.05). In addition, NSPCs on the EVAL-GYIGSR
      membrane were able to differentiate into neural lineage cells and differentiated
      neurons expressed functional synaptic activity. Basically, there was no
      significant difference between GYIGSR-immobilized and laminin-coated substrates
      for their ability to enhance migration and differentiation of NSPCs, suggesting
      that the immobilization of GYIGSR on the EVAL membrane was successful and the
      laminin-derived peptide YIGSR and laminin had similar effect on NSPC behaviors.
      However, it is non-permanent modification for coating laminin on the substrates
      to support cell survival after a long-term culture. In this study, differentiated
      neurons could still adhere to the EVAL-GYIGSR surface with functional synaptic
      activity after incubation for 20 days. Therefore, the bioactive EVAL-GYIGSR
      provided an alternative approach to improve migration and survival of NSPCs for
      neural tissue engineering applications.

PMID- 23006553
TI  - A facile and novel synthetic method for the preparation of hydroxyl capped
      fluorescent carbon nanoparticles.
AB  - A new type of fluorescent carbon based nanomaterial has drawn considerable
      attention due to their unique physicochemical properties. Carboxyl functionalized
      carbon nanoparticles are well documented in the literature. However, the carbonyl
      moiety in the carboxyl group considerably reduces the photoluminescence quantum
      yield. In this study, we present a direct, simple and novel synthetic route to
      produce hydroxyl functionalized fluorescent carbon nanoparticles derived from
      candle soot using organic base and surfactant which could be readily scaled up.
      The functionalization of carbon nanoparticle was confirmed by various
      spectroscopic techniques. (1)H NMR and FTIR measurements have been used to
      confirm the presence of sp(2) carbon in the form of aryl and hydroxyl moieties.
      MALDI-TOF Mass and TGA measurements further confirmed the functionalization.
      Structural characterization of these particles by Raman spectroscopy showed
      characteristic peaks located at 1333 and 1583 cm(-1) corresponding to diamond
      like (D) and graphite-like (G) bands of the carbon allotropes respectively. The
      minimum grain size of 7.3 nm was calculated using Raman spectra of the
      functionalized carbon nanoparticles which corroborate well with the results of
      dynamic light scattering (DLS) and TEM studies. UV-vis spectroscopic measurements
      displayed an absorption band at ca. 245 nm, which was consistent with the optical
      characteristics of functionalized carbon nanoparticles. PL measurements confirmed
      that the functionalized carbon nanoparticles have characteristic emission peak
      and shows fluorescence under blue light excitation. With a combination of free
      dispersion in water and attractive PL properties, these functionalized carbon
      nanoparticles hold promise for application in nanotechnology.

PMID- 23006554
TI  - Use of the self-assembly of tyrosine-containing bolaamphiphile molecules as a
      reactive template for metal deposition.
AB  - A novel bolaamphiphile molecule exploiting biochemical functionality was
      synthesized and self-assembled to form a spherical reactive template for the
      preparation of composite metallic nanoshells. A tyrosine-containing
      bolaamphiphile, bis(N-alpha-amido-tyrosine)-1,7-heptane dicarboxylate, self
      assembles instantaneously in an aqueous solution forming nanoscaled spheres.
      Instantaneous assembly of the prepared bolaamphiphile is driven by the polarity
      and stacking of phenol moiety in tyrosine. Through spectroscopic investigations,
      molecular interactions such as hydrogen bonding and pi-pi stacking of aromatic
      rings were found to induce the self-assembly of the molecule. The phenol moiety
      of tyrosine is exposed to the surface of the spherical assembly due to its
      polarity. Under basic conditions, the spherical assembly was used as a reactive
      template on which metal clusters were deposited. The surface-exposed phenol group
      reduced the silver ions to solid clusters, and these clusters were further
      exploited as catalysts for the gold layer deposition. This study illustrates that
      the bolaamphiphilic molecule with designed biochemical functionality provides a
      facile way to prepare supramolecular structures with chemical activity.

PMID- 23006555
TI  - Systematically investigations of conformation and thermodynamics of HSA adsorbed
      to different sizes of CdTe quantum dots.
AB  - Fluorescent quantum dots (QDs) have attracted great attention in biological and
      biomedical fields. In particular, for any potential application, the interaction
      of QDs with some biomolecules is much important. Herein, the interactions between
      QDs with different sizes and human serum albumin (HSA) were systematically
      investigated by UV-vis absorption spectra, fluorescence spectra and circular
      dichroism (CD) spectra under the physiological conditions. Four sizes of CdTe QDs
      with maximum emission of 520 nm (green QDs, GQDs), 568 nm (yellow QDs, YQDs), 620
      nm (red QDs, RQDs) and 680 nm (crimson QDs, CQDs) were tested. The fluorescence
      spectra results indicated that QDs could quench the fluorescence intensity of HSA
      effectively with a size-dependent relationship. The binding of QDs and HSA is a
      result of the formation of QDs-HSA complex and the electrostatic interaction
      plays a major role in stabilizing the complex. The modified Stern-Volmer
      quenching constants K(a) at different temperatures and corresponding
      thermodynamic parameters DeltaH, DeltaG and DeltaS were calculated. The
      conformational changes of HSA induced by QDs have been analyzed by CD spectra,
      and the results indicated that the biological activity of HSA was weakened in the
      present of QDs with bigger size.

PMID- 23006556
TI  - Highly efficient individual dispersion of single-walled carbon nanotubes using
      biocompatible dispersant.
AB  - Individual dispersion of single-walled carbon nanotubes (SWNTs) in biocompatible
      media is of particular interest for diverse biomedical and nanomedicine
      applications. Herein we present, for the first time, a neutral pH water-soluble
      chitosan derivative, chitosan-hydroxyphenyl acetamide (CHPA), prepared by
      functionalizing the amino groups of chitosan with 4-hydroxyphenyl acetic acid, as
      an efficient biocompatible dispersant to effectively debundle and individually
      disperse SWNTs in a neutral aqueous solution. For efficient individual dispersion
      of SWNTs, various process conditions such as centrifugation speed, sonication
      power, and CNT:dispersant ratio were optimized based on characterizations by
      atomic force microscopy, optical absorption spectroscopy, and Raman spectroscopy.
      Evaluation of the SWNT-CHPA solution showed superior individual dispersion to
      samples prepared using other biocompatible dispersants. The highly efficient
      individual dispersion of SWNTs with the biocompatible dispersant opens up
      possibilities for its applications in the bio- and nanomedical fields.

PMID- 23006557
TI  - Preparation, optimisation and characterisation of novel wound healing film
      dressings loaded with streptomycin and diclofenac.
AB  - Streptomycin (STP) and diclofenac (DLF) loaded film dressings were prepared by
      blending Polyox((r)) (POL) with four hydrophilic polymers
      [hydroxypropylmethylcellulose (HPMC), carrageenan (CAR), sodium alginate (SA) or
      chitosan (CS)] using glycerol (GLY) as plasticiser. The films were characterised
      by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X
      ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, texture
      analysis (tensile and swelling characteristics) and in vitro dissolution profiles
      using Franz diffusion cell. SEM showed homogeneous morphology for both blank
      (BLK) and drug loaded (DL) films. Films prepared by blending of POL with the
      other polymers showed a reduction in the crystallisation of POL in descending
      order of SA>CS>HPMC>CAR respectively. DSC and XRD showed no crystalline peaks of
      STP and DLF suggesting molecular dispersion of both drugs as well as possible
      drug interaction with negatively charged sulphate ions present in CAR. The DL
      films did not show any IR bands of both drugs, confirming the DSC and XRD
      results. POL-CAR-BLK films showed higher tensile strength (12.32+/-1.40 MPa) than
      the POL-CAR-DL films (9.52+/-1.12 MPa). DL films plasticised with 25%w/w GLY
      revealed soft and tough (tensile strength 1.02+/-0.28 MPa, % elongation 1031.33+/
      16.23) formulations. The swelling capacities of POL-CAR-BLK and POL-CAR-DL films
      were (733.17+/-25.78%) and (646.39+/-40.39%), increasing to (1072.71+/-80.30%)
      and (1051+/-86.68%) for POL-CAR-BLK-25% GLY and POL-CAR-DL-25% GLY respectively.
      POL-CAR-DL films showed significantly (n=3, p<0.0318) lower cumulative release of
      STP and DLF (52.11+/-1.34, 55.26+/-2.25) compared to POL-CAR-DL-25% GLY films
      (60.07+/-1.56, 63.39+/-1.92) respectively.

PMID- 23006559
TI  - Surface modified and medicated polyurethane materials capable of controlling
      microorganisms causing foot skin infection in athletes.
AB  - Foot odor and foot infection are major problems of athletes and persons with
      hyperhidrosis. Many shoes especially sports shoes have removable cushion
      insoles/foot beds for foot comfort. Polyurethane (PU) foam and elastomer have
      been used as cushion insole in shoes. In the present work, new insole materials
      based on porous viscoelastic PU sheets having hydrophilic property and
      antimicrobial drug coating to control foot infection and odor were developed.
      Bacteria and fungus that are causing infection and bad odor of the foot of
      athletes were isolated by microbial cell culturing of foot sweat. The surface of
      porous viscoelastic PU sheets was modified using hydrophilic polymers and coated
      with antimicrobial agent, silver sulfadiazine (SS). The surface modified PU
      sheets were characterized using ATR-FTIR, TGA, DSC, SEM, contact angle
      measurement and water absorption study. Results had shown that modified PU sheets
      have hydrophilicity greater than that of original PU sheet. FTIR spectra and SEM
      pictures confirmed modification of PU surface with hydrophilic polymers and
      coating with SS. Minimum inhibitory concentration studies indicated that SS has
      activity on all isolated bacteria of athletic foot sweat. The maximum inhibition
      was found for Pseudomonas (20mm) followed by Micrococci (17 mm), Diphtheroids (16
      mm) and Staphylococci (12 mm). During perspiration of foot the hydrophilic
      polymers on PU surface will swell and release SS. Future work will confirm the
      application of these materials as inserts in athletic shoes.

PMID- 23006558
TI  - Cell interaction study method using novel 3D silica nanoneedle gradient arrays.
AB  - Understanding cellular interactions with culture substrate features is important
      to advance cell biology and regenerative medicine. When surface topographical
      features are considerably larger in vertical dimension and are spaced at least
      one cell dimension apart, the features act as 3D physical barriers that can guide
      cell adhesion, thereby altering cell behavior. In the present study, we
      investigated competitive interactions of cells with neighboring cells and matrix
      using a novel nanoneedle gradient array. A gradient array of nanoholes was
      patterned at the surface of fused silica by single-pulse femtosecond laser
      machining. A negative replica of the pattern was extracted by nanoimprinting with
      a thin film of polymer. Silica was deposited on top of the polymer replica to
      form silica nanoneedles. NIH 3T3 fibroblasts were cultured on silica nanoneedles
      and their behavior was studied and compared with those cultured on a flat silica
      surface. The presence of silica nanoneedles was found to enhance the adhesion of
      fibroblasts while maintaining cell viability. The anisotropy in the arrangement
      of silica nanoneedles was found to affect the morphology and spreading of
      fibroblasts. Additionally, variations in nanoneedle spacing regulated cell-matrix
      and cell-cell interactions, effectively preventing cell aggregation in areas of
      tightly-packed nanoneedles. This proof-of-concept study provides a reproducible
      means for controlling competitive cell adhesion events and offers a novel system
      whose properties can be manipulated to intimately control cell behavior.

PMID- 23006560
TI  - Synthesis, characterization, and mineralization of polyamide-6/calcium lactate
      composite nanofibers for bone tissue engineering.
AB  - Polyamide-6 nanofibers containing calcium lactate (CL) on their surface were
      prepared by neutralization of lactic acid (LA) in core-shell structured polyamide
      6/LA electrospun fibers. First, simple blending of LA with polyamide-6 solution
      was used for electrospinning which interestingly formed a thin LA layer around
      polyamide-6 nanofibers (core-shell structure) and then subsequent conversion of
      this LA into calcium lactate via neutralization using calcium base. FE-SEM and
      TEM images revealed that plasticizer capacity of LA led the formation of point
      bonded structure due to the formation of shell layer of LA and core of polyamide
      6. The bone formation ability of polyamide-6/calcium lactate composite fibers was
      evaluated by incubating in biomimetic simulated body fluid (SBF). The SBF
      incubation test confirmed the faster deposition of large amount of calcium
      phosphate around the composite polyamide-6/calcium lactate fibers compared to
      pristine polyamide-6. This study demonstrated a simple post electrospinning
      calcium compound coating technique of polymeric nanofibers for enhancing the bone
      biocompatibility of polyamide-6 fibers.

PMID- 23006561
TI  - Interaction between Escherichia coli and TiO2 nanoparticles in natural and
      artificial waters.
AB  - Seine River water was used as a natural environmental medium to quantify the
      ecotoxicological impact of three types of manufactured titanium dioxide (TiO(2))
      nanoparticles toward the model bacterium Escherichia coli. Under ambient light, a
      significant toxicity starting at 10 ppm of TiO(2) in water was observed. Presence
      of the anatase polymorph slightly increased the toxicity in comparison to pure
      rutile samples. Furthermore, the toxicity was found to be lower at pH 5 compared
      to Seine water (pH 8). To assess the nanoparticles state of dispersion and their
      interactions with bacteria, cryogenic transmission electron microscopy (TEM) and
      zeta potential measurements were performed. A higher sorption of nanoparticle
      aggregates on cells is observed at pH 5 compared to Seine water. This allows
      concluding that the observed toxicity is not directly linked to the particles
      sorption onto the cell surfaces. In spite of stronger interaction between cells
      and nanoparticles at pH 5, a bacterial subpopulation apparently non-interacting
      with nanoparticles is evidenced by both TEM and zeta potential measurements. Such
      heterogeneities in cell populations can increase global bacterial resistance to
      TiO(2) nanoparticles.

PMID- 23006562
TI  - Characterisation, surface properties and biological activity of a biosurfactant
      produced from industrial waste by Candida sphaerica UCP0995 for application in
      the petroleum industry.
AB  - The development of less toxic, biodegradable, surfactants, such as
      biosurfactants, is a key strategy for acquiring environmentally friendly
      compounds. The aim of the present study was to employ an optimised medium
      containing 9% ground nut oil refinery residue and 9% corn steep liquor for the
      production of a biosurfactant by Candida sphaerica. Fermentation was carried out
      at 28  degrees C and 200 rpm for 144 h. Biosurfactant yield was 9 g/l. The
      biosurfactant reduced the surface tension of the medium to 25 mN/m, with a
      critical micelle concentration of 0.025%. The product demonstrated stability with
      regard to surface tension reduction and emulsification in a range of temperatures
      (5-120  degrees C) and pH values (2-12) as well as tolerance to high
      concentrations of NaCl (2-10%). Hydrophobicity tests indicate two possible
      insoluble substrate uptake mechanisms: direct interfacial uptake and
      biosurfactant-mediated transfer (cell contact with emulsified or solubilised
      hydrocarbons). The biosurfactant was characterised as an anionic glycolipid
      consisting of 70% lipids and 15% carbohydrates and demonstrated no toxicity to
      the microcrustacean Artemia salina or the vegetables Brassica oleracea, Solanum
      gilo, Lactuca sativa L. and Brassica oleracea L. The biosurfactant recovered 95%
      of motor oil adsorbed to a sand sample, demonstrating considerable potential for
      use in bioremediation processes, especially in the petroleum industry.

PMID- 23006563
TI  - Improved biocompatibility of poly (styrene-b-(ethylene-co-butylene)-b-styrene)
      elastomer by a surface graft polymerization of hyaluronic acid.
AB  - Hyaluronic acid (HA) is an important component of extracellular matrix (ECM) in
      many tissues, providing a hemocompatible and supportive environment for cell
      growth. In this study, glycidyl methacrylate-hyaluronic acid (GMHA) was first
      synthesized and verified by proton nuclear magnetic resonance ((1)H NMR)
      spectroscopy. GMHA was then grafted to the surface of biomedical elastomer poly
      (styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) via an UV-initiated
      polymerization, monitored by attenuated total reflectance Fourier transform
      infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The
      further improvement of biocompatibility of the GMHA-modified SEBS films was
      assessed by platelet adhesion experiments and in vitro response of murine
      osteoblastic cell line MC-3T3-E1 with the virgin SEBS surface as the reference.
      It showed that the surface modification with HA strongly resisted platelet
      adhesion whereas improved cell-substrate interactions.

PMID- 23006564
TI  - Polyphenol-SiO2 hybrid biosorbent for heavy metal removal. Yerba mate waste (Ilex
      paraguariensis) as polyphenol source: kinetics and isotherm studies.
AB  - A low-cost biosorbent hybrid material ready for application was obtained in this
      work. Yerba mate (Ilex paraguariensis) milling residual dust was used as a
      polyphenol source by ethanolic extraction. Polyphenols were immobilized within a
      SiO(2) matrix to form an interpenetrated polymer after glutaraldehyde cross
      linking. Pb(II), Cr(III) and Cr(VI) were chosen as model metals for adsorption.
      The hybrid materials were characterized by Fourier Transform Infrared
      Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray
      Spectroscopy (EDS) and Nitrogen Adsorption Isotherms. Adsorption experimental
      data were analysed using Langmuir, Freundlich, Dubinin-Radushkevich, Temkin,
      Redlich-Peterson, Sips and Toth isotherm models along with the evaluation of
      adsorption energy and standard free energy (DeltaG degrees ). The adsorption was
      observed to be pH dependent. The main mechanism of metal adsorption was found to
      be a spontaneous charge associated interaction. Electron Spin Resonance (ESR)
      spectroscopy confirmed that Cr(VI) adsorption was an adsorption-coupled reaction
      and the adsorbed specie was Cr(V). The hybrid matrix probed its adsorption
      capacity of Cr(III) in a non-treated tannery wastewater.

PMID- 23006565
TI  - Nanospines incorporation into the structure of the hydrophobic cryogels via novel
      cryogelation method: an alternative sorbent for plasmid DNA purification.
AB  - In this study, it was aimed to prepare hydrophobic cryogels for plasmid DNA
      (pDNA) purification from Escherichia coli lysate. The hydrophobicity was achieved
      by incorporating a hydrophobic ligand, N-methacryloyl-(L)-phenylalanine (MAPA),
      into the cryogel backbone. In addition to the conventional cryogelation process,
      freeze-drying step was included to create nanospines. Three different cryogels
      {poly(2-hydoxyethyl methacrylate-N-methacryloyl-L-phenylalanine)-freeze dried,
      [P(HEMA-MAPA)-FD]; poly(2-hydoxyethyl methacrylate-N-methacryloyl-L
      phenylalanine, [P(HEMA-MAPA)] and poly(2-hydoxyethyl methacrylate)-freeze dried,
      [P(HEMA)-FD]} were prepared, characterized, and used for DNA (salmon sperm DNA)
      adsorption studies from aqueous solution. The specific surface areas of cryogels
      were determined to be 21.4 m(2)/g for P(HEMA)-FD, 17.65 m(2)/g for P(HEMA-MAPA)
      and 36.0 m(2)/g for P(HEMA-MAPA)-FD. The parameters affecting adsorption such as
      temperature, initial DNA concentration, salt type and concentration were examined
      in continuous mode. The maximum adsorption capacities were observed as 45.31 mg
      DNA/g, 27.08 mg DNA/g and 1.81 mg DNA/g for P(HEMA-MAPA)-FD, P(HEMA-MAPA) and
      P(HEMA)-FD, respectively. Desorption process was performed using acetate buffer
      (pH 5.50) without salt. First, pDNA was isolated from E. coli lysate and the
      purity of pDNA was then determined by agarose gel electrophoresis. Finally, the
      chromatographic performance of P(HEMA-MAPA)-FD cryogel for pDNA purification was
      tested in FPLC. The resolution (R(s)) was 2.84, and the specific selectivity for
      pDNA was 237.5-folds greater than all impurities.

PMID- 23006566
TI  - Further investigation of nanostructured lipid carriers as an ocular delivery
      system: in vivo transcorneal mechanism and in vitro release study.
AB  - This study was designed to provide further understanding of transcorneal
      mechanism of nanostructured lipid carriers (NLC). NLC labeled with fluorescent
      marker rhodamine B or coumarin-6 were produced by a melt emulsification method.
      By confocal laser scanning microscopy (CLSM), the interaction of NLC with corneal
      epithelia was traced and evaluated in rabbits in vivo. Thermal stability of the
      markers and the amorphous state were detected using thermogravimetric analysis
      (TGA) and differential scanning calorimeter (DSC). The labeled NLC were
      characterized to be solid spherical in shape with an average diameter of 70 nm
      and zeta potential of -8 mV by transmission electron microscopy and dynamic light
      scattering, respectively. CLSM results demonstrated NLC were not directly
      internalized by corneal epithelia, whereas the markers themselves transferred
      from NLC to corneal epithelia with subsequent staining of intracellular
      lipophilic compartments. Furthermore, the in vitro release study using liposome
      dispersions as mimic biomembranes demonstrated an efficient transfer of
      fluorescence marker into the liposomes. This implied the deceptive particle
      uptake was due to a collision-induced process, during which the rapid transfer of
      fluorescence marker occurred by forming a complex between the nanoparticles and
      the biomembranes. Thus, these evidences provide further insights into NLC as an
      ocular delivery system.

PMID- 23006567
TI  - Influence of initial pH on the precipitation and crystal morphology of calcium
      carbonate induced by microbial carbonic anhydrase.
AB  - The dynamics of calcium carbonate (CaCO(3)) precipitation induced by microbial
      intracellular or extracellular carbonic anhydrase (CA) at initial pH 6.0, 6.5,
      7.0 and 8.0 were investigated through the gaseous diffusion method. The results
      indicated that both the intracellular and extracellular CA could promote CaCO(3)
      precipitation. The Ca(2+) ions in the enzymatic systems at initial pH 8.0 were
      completely deposited at 48 h, which were respectively 21 h, 15 h and 14 h earlier
      compared with that at initial pH 6.0, pH 6.5 and pH 7.0, indicating that higher
      pH favored CaCO(3) precipitation in the experimental pH range, and was beneficial
      to the catalytic action of microbial CA on CaCO(3) precipitation. In addition,
      XRD analysis indicated that the CaCO(3) precipitates were mainly calcite crystals
      in the presence of microbial CA. With increasing deposition time, the crystals
      gradually changed from prism shape to pyramid-like or irregular polyhedral shape
      based on FESEM analysis.

PMID- 23006568
TI  - Biosynthesis of silver nanoparticles using Alternanthera sessilis (Linn.) extract
      and their antimicrobial, antioxidant activities.
AB  - The present work focuses the use of the aqueous extract of Alternanthera sessilis
      Linn. (Amaranthaceae) in producing silver nanoparticles (AgNPs) from silver
      nitrate aqueous. Phytochemical analysis of the extract revealed the presence of
      alkaloid, tannins, ascorbic acid, carbohydrates and proteins and they serve as
      effective reducing and capping agents for converting silver nitrate into
      nanoparticles. The synthesized silver nanoparticles (AgNPs) were also tested for
      proteins and ascorbic acid. Its pH was also determined (5.63). The AgNPs obtained
      was characterized by UV-vis spectroscopy, FT-IR spectroscopy, SEM, Zeta sizer and
      TG-DSC. SEM images which revealed the presence of various shapes and sizes. FT-IR
      spectrum showed the AgNPs having a coating of proteins indicating a dual role of
      bio-molecules responsible for capping and efficient stabilization of the silver
      nanoparticles. Presence of impurities and melting point profile were screened by
      TG-DSC analyzer. AgNPs were synthesized from the silver nitrate through the
      reducing power of ascorbic acid present in A. sessilis leaves. In this study, we
      also investigated antimicrobial and antioxidant activity of green synthesized
      AgNPs. The antimicrobial activity is investigated by Bauer et al.'s method.
      Antioxidant activity was done by DPPH method.

PMID- 23006569
TI  - Antibacterial effects of silver nanoparticles on gram-negative bacteria:
      influence on the growth and biofilms formation, mechanisms of action.
AB  - Antibacterial action of silver nanoparticles (AgNP) on Gram-negative bacteria
      (planctonic cells and biofilms) is reported in this study. AgNP of 8.3 nm in
      diameter stabilized by hydrolyzed casein peptides strongly inhibited biofilms
      formation of Escherichia coli AB1157, Pseudomonas aeruginosa PAO1 and Serratia
      proteamaculans 94 in concentrations of 4-5 MUg/ml, 10 MUg/ml and 10-20 MUg/ml,
      respectively. The viability of E. coli AB1157 cells in biofilms was considerably
      reduced by AgNP concentrations above 100 to -150 MUg/ml. E. coli strains with
      mutations in genes responsible for the repair of DNA containing oxidative lesions
      (mutY, mutS, mutM, mutT, nth) were less resistant to AgNP than wild type strains.
      This suggests that these genes may be involved in the repair of DNA damage caused
      by AgNP. E. coli mutants deficient in excision repair, SOS-response and in the
      synthesis of global regulators RpoS, CRP protein and Lon protease present similar
      resistance to AgNP as wild type cells. LuxI/LuxR Quorum Sensing systems did not
      participate in the control of sensitivity to AgNP of Pseudomonas and Serratia. E.
      coli mutant strains deficient in OmpF or OmpC porins were 4-8 times more
      resistant to AgNP as compared to the wild type strain. This suggests that porins
      have an important function related AgNP antibacterial effects.

PMID- 23006570
TI  - Nonenzymatic glucose sensor based on nickel(II)oxide/ordered mesoporous carbon
      modified glassy carbon electrode.
AB  - A highly sensitive and selective nonenzymatic glucose sensor based on
      electrodepositing NiO nanoparticles on ordered mesoporous carbon (named as
      NiO/OMC) modified glassy carbon electrode (GCE) was constructed. The synthesized
      OMC was characterized by X-ray diffraction, and the morphology images of OMC
      nanoparticle and NiO/OMC nanocomposite were characterized by scanning electron
      microscope. Electrochemical behaviors of glucose at the NiO/OMC/GCE were
      investigated by cyclic voltammetry and amperometry, and the modified electrode
      showed excellent electrochemical activity toward the oxidation of glucose. At the
      optimum conditions, the calibration curve for glucose determination was linear in
      the range of 2-1000 MUM with a fast response time (<2 s), and a high sensitivity
      of 834.8 MUA mM(-1) cm(-2) and a low detection limit (S/N=3) of 0.65 MUM were
      obtained. In addition, the proposed sensor was successfully applied to analyze
      glucose level in human blood serum samples.

PMID- 23006571
TI  - Effects of barium titanate nanoparticles on proliferation and differentiation of
      rat mesenchymal stem cells.
AB  - Nanomaterials hold great promise in the manipulation and treatments of
      mesenchymal stem cells, since they allow the modulation of their properties and
      differentiation. However, systematic studies have to be carried out in order to
      assess their potential toxicological effects. The present study reports on
      biocompatibility evaluation of glycol-chitosan coated barium titanate
      nanoparticles (BTNPs) on rat mesenchymal stem cells (MSCs). BTNPs are a class of
      ceramic systems which possess interesting features for biological applications
      thanks to their peculiar dielectric and piezoelectric properties. Viability was
      evaluated up to 5 days of incubation (concentrations in the range 0-100 MUg/ml)
      both quantitatively and qualitatively with specific assays. Interactions
      cells/nanoparticles were further investigated with analysis of the cytoskeleton
      conformation, with SEM and TEM imaging, and with AFM analysis. Finally,
      differentiation in adipocytes and osteocytes was achieved in the presence of high
      doses of BTNPs, thus highlighting the safety of these nanostructures towards
      mesenchymal stem cells.

PMID- 23006572
TI  - Detection of label-free H2O2 based on sensitive Au nanorods as sensor.
AB  - A rapid, reproducible, cost-effective approaches for the detection of hydrogen
      peroxide has been developed based on the change of localized surface plasmon
      resonance (LSPR) peak of Au nanorods (NRs). Au NRs were prepared by silver ion
      assisted seed-mediated method, which are characterized by UV-vis spectroscopy and
      transmission electron microscopy. The longitudinal plasmon band of Au nanorods is
      highly sensitive to their aspect ratios so that LSPR peak of Au NRs was shift
      with change of their aspect ratios. Hydrogen peroxide (H(2)O(2)) with high
      oxidation potential can decompose Au NRs. As a result, Au NRs can be shortened
      through an oxidation reaction by H(2)O(2). After shortening Au NRs, the LSPR
      peaks show blue shift. The LSPR peak of Au NRs displays the dependence of
      spectral shift on concentration of H(2)O(2). It provides a more simple and
      sensitive method for detecting H(2)O(2).

PMID- 23006573
TI  - Utilization of environmental waste cyanobacteria as a pesticide carrier: studies
      on controlled release and photostability of avermectin.
AB  - Cyanobacteria (Cyb), an environment waste, was first utilized as a carrier for
      controlled release of avermectin (Av) and improvement of pesticide
      photostability. Microalgae powder prepared from Cyb blooms was characterized by
      elemental analysis (EA), X-ray photoelectron spectroscopy (XPS), infrared
      spectroscopy (IR), optical microscopy, and scanning electron microscopy (SEM).
      The globular morphology and the size (~3.5MUm) of Cyb do not change
      significantly, with increase of roughness, after Av adsorption and Carbopol
      coating. Av manifests considerable binding affinity to Cyb in isopropanol and
      adsorption decreases in more polar solvents at 25 degrees C. An extended release
      of Av from Cyb-Av in ethanol/water (v/v, 4:1) mixture was obtained and the
      release was further controlled by the Carbopol resin coated on Cyb-Av. Thicker
      Carbopol coating results in larger lag time (t(0)), slower release rate, and less
      total release amount. The release process was found to be controlled by a
      diffusion mechanism, but was strongly affected by polymer matrix-Av interaction
      and polymer relaxation. Finally, adsorbed Av on Cyb exhibits much greater UV
      stability than free Av.

PMID- 23006574
TI  - Antifouling properties of poly(dimethylsiloxane) surfaces modified with
      quaternized poly(dimethylaminoethyl methacrylate).
AB  - A quaternized poly(dimethylaminoethyl methacrylate)-grafted
      poly(dimethylsiloxane) (PDMS) surface (PDMS-QPDMAEMA) was successfully prepared
      in this study via solution-phase oxidation reaction and surface-initiated atom
      transfer radical polymerization (SI-ATRP) using dimethylaminoethyl methacrylate
      (DMAEMA) as initial monomer. PDMS substrates were first oxidized in
      H(2)SO(4)/H(2)O(2) solution to transform the SiCH(3) groups on their surfaces
      into SiOH groups. Subsequently, a surface initiator for ATRP was immobilized onto
      the PDMS surface, and DMAEMA was then grafted onto the PDMS surface via copper
      mediated ATRP. Finally, the tertiary amino groups of PolyDMAEMA (PDMAEMA) were
      quaternized by ethyl bromide to provide a cationic polymer brush-modified PDMS
      surface. Various characterization techniques, including contact angle
      measurements, attenuated total reflection infrared spectroscopy, and X-ray
      photoelectron spectroscopy, were used to ascertain the successful grafting of the
      quaternized PDMAEMA brush onto the PDMS surface. Furthermore, the wettability and
      stability of the PDMS-QPDMAEMA surface were examined by contact angle
      measurements. Antifouling properties were investigated via protein adsorption, as
      well as bacterial and cell adhesion studies. The results suggest that the PDMS
      QPDMAEMA surface exhibited durable wettability and stability, as well as
      significant antifouling properties, compared with the native PDMS and PDMS
      PDMAEMA surfaces. In addition, our results present possible uses for the PDMS
      QPDMAEMA surface as adhesion barriers and antifouling or functional surfaces in
      PDMS microfluidics-based biomedical applications.

PMID- 23006575
TI  - Study on nicotinamide adenine dinucleotide adsorbed at nano-boehmite/water and
      nano-corundum/water interfaces.
AB  - In this study, the adsorption behaviors of nicotinamide adenine dinucleotide
      (NAD(+)) on nano-boehmite (gamma-AlOOH) and nano-corundum (gamma-Al(2)O(3))
      surfaces were investigated. The results showed that NAD(+) was predominantly
      adsorbed at the boehmite/water and corundum/water interfaces in outer-sphere
      fashions by electrostatic interaction between NAD(+) phosphate and surface
      hydroxyl groups. However, the features of ATR-FTIR spectra suggested that some
      minor inner-sphere complex should be considered at low pH conditions on corundum
      surface, which was consistent with the effect of NAD(+) on dissolution rate of
      corundum. In addition, the adsorption data well fitted with Langmuir and
      Freundlich isotherms on the boehmite and corundum surfaces, respectively. Also,
      the Gibbs adsorption energy was negative on the boehmite surface, which indicated
      that the adsorption behavior was spontaneous.

PMID- 23006576
TI  - Effects of simvastatin-loaded polymeric micelles on human osteoblast-like MG-63
      cells.
AB  - To develop an optimized simvastatin (SV) delivery device for bone regeneration,
      SV-loaded poly(ethylene glycol)-poly(epsilon-caprolactone) (PECL) micelles were
      constructed. The micelles had an average size of 80 nm. The in vitro release
      behavior of SV from the micelles showed prolonged release compared to the free
      SV. The following four groups were tested in a cytologic experiment: a free SV
      group, a SV-loaded micelle group with SV concentrations ranging from 2.5*10(-6)
      to 2.5*10(-10) M, a drug-free micelle group and a blank control group. The effect
      of SV-loaded micelles on osteoblast-like MG-63 cells was determined via analysis
      of cell proliferation, alkaline phosphatase activity, and cell calcification. In
      addition, the mRNA and protein expression of the BMP-2 gene were determined with
      real-time fluorescence quantitative polymerase chain reaction and western blot
      techniques, respectively. The results show that SV-loaded PECL micelles cause
      effective suppression of the osteoblast early proliferation inhibition,
      stimulation of osteoblast differentiation and mineralization, and stimulation of
      the BMP-2 expression. Therefore, SV-loaded PECL micelles are predicted to have
      great potential in bone regeneration applications.

PMID- 23006578
TI  - Motor recovery mechanisms in patients with middle cerebral artery infarct: a mini
      review.
AB  - Previous studies on the mechanisms of motor recovery in patients with middle
      cerebral artery (MCA) infarct except for the studies on cortical peri-infarct
      reorganization after primary motor cortex infarct were reviewed. Eight studies
      were classified and reviewed by the following four motor recovery mechanisms:
      contribution of premotor cortex, subcortical peri-infarct reorganization,
      ipsilateral motor pathway, and contribution of aberrant motor pathway. MCA
      infarct is the most common type among the arterial territory infarcts. In
      addition, MCA territory is important for motor function because it comprises the
      corticospinal tract, the corticoreticulospinal tract and the neural tracts which
      are related with apraxia (superior longitudinal fasciculus and corticofugal
      fibers from the premotor cortex). In spite of the significance of the MCA
      territory for motor function, fewer studies have reported on the mechanisms of
      motor recovery in MCA infarct compared to total number of studies about cerebral
      infarct. In addition, the majority of these studies have focused on the
      corticospinal tract. Therefore, the total number of studies on this topic should
      be increased. We believe that further studies comprising other neural tracts
      except for the corticospinal tract including the extrapyramidal tracts such as
      the corticoreticulospinal and neural tracts which are related with apraxia, are
      necessary.

PMID- 23006577
TI  - Factors influencing participant enrolment in a diabetes prevention program in
      general practice: lessons from the Sydney diabetes prevention program.
AB  - BACKGROUND: The effectiveness of lifestyle interventions in reducing diabetes
      incidence has been well established. Little is known, however, about factors
      influencing the reach of diabetes prevention programs. This study examines the
      predictors of enrolment in the Sydney Diabetes Prevention Program (SDPP), a
      community-based diabetes prevention program conducted in general practice, New
      South Wales, Australia from 2008-2011. METHODS: SDPP was an effectiveness trial.
      Participating general practitioners (GPs) from three Divisions of General
      Practice invited individuals aged 50-65 years without known diabetes to complete
      the Australian Type 2 Diabetes Risk Assessment tool. Individuals at high risk of
      diabetes were invited to participate in a lifestyle modification program. A
      multivariate model using generalized estimating equations to control for
      clustering of enrolment outcomes by GPs was used to examine independent
      predictors of enrolment in the program. Predictors included age, gender,
      indigenous status, region of birth, socio-economic status, family history of
      diabetes, history of high glucose, use of anti-hypertensive medication, smoking
      status, fruit and vegetable intake, physical activity level and waist
      measurement. RESULTS: Of the 1821 eligible people identified as high risk, one
      third chose not to enrol in the lifestyle program. In multivariant analysis,
      physically inactive individuals (OR: 1.48, P = 0.004) and those with a family
      history of diabetes (OR: 1.67, P = 0.000) and history of high blood glucose
      levels (OR: 1.48, P = 0.001) were significantly more likely to enrol in the
      program. However, high risk individuals who smoked (OR: 0.52, P = 0.000), were
      born in a country with high diabetes risk (OR: 0.52, P = 0.000), were taking
      blood pressure lowering medications (OR: 0.80, P = 0.040) and consumed little
      fruit and vegetables (OR: 0.76, P = 0.047) were significantly less likely to take
      up the program. CONCLUSIONS: Targeted strategies are likely to be needed to
      engage groups such as smokers and high risk ethnic groups. Further research is
      required to better understand factors influencing enrolment in diabetes
      prevention programs in the primary health care setting, both at the GP and
      individual level.

PMID- 23006579
TI  - Phenazine methosulfate decreases HIF-1alpha accumulation during the exposure of
      cells to hypoxia.
AB  - In HEK293 cells, exposure to various NAD(P)H oxidants, including phenazine
      methosulfate (PMS), that non-enzymatically oxidize intracellular NAD(P)H to
      NAD(P), decreased hypoxia-induced hypoxia-inducible factor 1 (HIF-1alpha)
      accumulation. RT-PCR and cycloheximide inhibition experiments indicated that PMS
      induced HIF-1alpha decrease is involved in post-translational degradation during
      hypoxia. The decrease in HIF-1alpha caused by PMS was not eliminated by
      proteasome inhibitor MG132. Moreover, the increase in HIF-1alpha induced by
      exposure to MG132 alone in normoxia was diminished by PMS. In contrast,
      calpastatin peptide, a calpain inhibitor, fully prevented PMS-induced reduction
      in HIF-1alpha in hypoxic cells. These data suggest that the decreased stability
      of HIF-1alpha induced by PMS is due to the activation by PMS of a protein
      degradation system that is independent of the ubiquitin-proteasome pathway.

PMID- 23006580
TI  - Identification of the replication region of a 111-kb circular plasmid from
      Rhodococcus opacus B-4 by lambda Red recombination-based deletion analysis.
AB  - The replication region of the 111-kb circular plasmid pKNR from Rhodococcus
      opacus B-4 was identified. A PCR-based deletion analysis using the lambda Red
      recombination technique followed by restriction digestion and PCR-amplification
      analyses revealed that a 2.5-kb fragment covering one putative open reading frame
      (ORF) was involved in the replication of pKNR. The product of this ORF showed
      significant similarity to a functionally unknown protein encoded in the
      replication region of the 70-kb circular plasmid of Clavibacter michiganensis and
      to ones in other bacterial large circular plasmids. These observations suggest
      that the product of the identified ORF and its orthologs can serve as novel
      replication proteins for large circular bacterial plasmids.

PMID- 23006581
TI  - Intrinsic endobronchial obstructions in children from Turkey: evaluation of 2,555
      flexible bronchoscopic procedures.
AB  - BACKGROUND: Endobronchial obstructions are rarely seen in children and are often
      misdiagnosed resulting in delay of definitive treatment. A variety of diseases
      can cause endobronchial obstructions in childhood, but data is limited as to the
      frequency, distribution and clinical characteristics of endobronchial
      obstructions diagnosed with flexible bronchoscopy (FB). OBJECTIVE: To document
      endobronchial obstructions detected by FB. METHODS: FB results from three
      pediatric pulmonology centers in Istanbul were evaluated. RESULTS: A total of
      2,555 children underwent an FB procedure during the study period. Endobronchial
      obstructions were detected in 10% (n = 256) of the patients. Among FB in patients
      who had endobronchial obstructions, the four most common indications for
      bronchoscopy were persistent infiltrations (30%, n = 72), persistent wheezing
      (28%, n = 70), chronic cough (26%, n = 66) and atelectasis (23%, n = 59). The
      most common endobronchial obstructions detected in the patients were aspirated
      foreign bodies (35.9%, n = 92), endobronchial tuberculosis (31.6%, n = 81),
      mucous plugs occluding airway (16.7%, n = 43) and granulation scars (6%, n = 16).
      Other pathologies included hydatid cysts (n = 5), hemangiomas (n = 5), tumors (n
      = 5), submucosal nodules (n = 5) and polyps (n = 4). Endobronchial obstructions
      were most commonly located in the right bronchus (51%, n = 130) followed by the
      left bronchus (33%, n = 85), bilaterally (8%, n = 21) and trachea (8%, n = 20).
      CONCLUSIONS: Endobronchial obstructions can be caused by a number of different
      diseases which require various medical or surgical treatments. In the presence of
      clinical or radiological findings suggesting an endobronchial obstruction, FB
      should be performed promptly.

PMID- 23006582
TI  - Blood oxidative-stress markers during a high-altitude trek.
AB  - Oxidative stress occurs as a result of altitude-induced hypobaric hypoxia and
      physical exercise. The effect of exercise on oxidative stress under hypobaric
      hypoxia is not well understood. PURPOSE: To determine the effect of high-altitude
      exercise on blood oxidative stress. Nine male participants completed a 2-d trek
      up and down Mt Rainer, in North America, at a peak altitude of 4,393 m. Day 1
      consisted of steady-pace climbing for 6.25 hr to a final elevation of 3,000 m.
      The 4,393-m summit was reached on Day 2 in approximately 5 hr. Climb-rest
      intervals varied but were consistent between participants, with approximately 14
      hr of total time including rest periods. Blood samples were assayed for
      biomarkers of oxidative stress and antioxidant potential at the following time
      points: Pre (before the trek), 3Kup (at ascent to 3,000 m), 3Kdown (at 3,000 m on
      the descent), and Post (posttrek at base elevation). Blood serum variables
      included ferric-reducing antioxidant potential (FRAP), Trolox equivalent
      antioxidant capacity (TEAC), protein carbonyls (PC), and lipid hydroperoxides.
      Serum FRAP was elevated at 3Kup and 3Kdown compared with Pre and Post values (p =
      .004, 8% and 11% increase from Pre). Serum TEAC values were increased at 3Kdown
      and Post (p = .032, 10% and 18% increase from Pre). Serum PC were elevated at
      3Kup and 3Kdown time points (p = .034, 194% and 138% increase from Pre), while
      lipid hydroperoxides were elevated Post only (p = .004, 257% increase from Pre).
      CONCLUSIONS: Findings indicate that high-altitude trekking is associated with
      increased blood oxidative stress.

PMID- 23006583
TI  - Erythropoietin ameliorates oxidative stress and tissue injury following renal
      ischemia/reperfusion in rat kidney and lung.
AB  - OBJECTIVE: To study the effect of erythropoietin (EPO) treatment on renal and
      lung injury following renal ischemia/reperfusion (I/R). MATERIALS AND METHODS:
      Thirty male Wistar rats were assigned to three groups of 10 rats each. The first
      group was sham-operated, the second was subjected to renal I/R (30 min of
      ischemia followed by 24 h of reperfusion). The third group was subjected to renal
      I/R and treated with EPO in two doses: the first dose 1 h prior to ischemia
      (1,000 U/kg) and the second dose 6 h after ischemia (1,000 U/kg). RESULTS: The
      renal and lung tissue injury index, tissue serum blood urea nitrogen and
      creatinine (Cr) were higher in the renal I/R group compared to the renal I/R +
      EPO group; the difference was statistically significant (p < 0.05). Kidney and
      lung tissue glutathione peroxidase and superoxide dismutase levels were higher in
      the renal I/R + EPO group than the renal I/R group; the difference was also
      statistically significant (p < 0.05). CONCLUSION: The data showed that EPO
      pretreatment could be effective in reducing renal and lung injury following renal
      I/R and could improve the cellular antioxidant defense system. Hence EPO
      pretreatment may be effective for attenuating renal and lung injury after renal
      I/R-induced injury during surgical procedures, hypotension, renal transplantation
      and other conditions inducing renal I/R.

PMID- 23006585
TI  - Clinical relevance of HCV antiviral drug resistance.
AB  - The approval of direct-acting antiviral agents (DAAs) against the hepatitis C
      virus (HCV) NS3 protease revolutionized antiviral therapy in chronic hepatitis C.
      They mark the beginning of an era with drugs designed to inhibit specific viral
      proteins involved in the virus life cycle rather than the nonspecific antiviral
      activity of interferon. Upcoming generations of antivirals are expected that lead
      to viral eradication in most patients who undergo treatment with hope held for
      years that HCV can be cured without interferon. Antiviral drug resistance plays a
      key role in DAA-treatment failure. Knowledge on molecular escape mechanisms of
      resistant variants, their time to wild-type reversal and potential persistence is
      of upmost importance to design treatment strategies for patients with previous
      DAA-treatment failure.

PMID- 23006584
TI  - Are subtype differences important in HIV drug resistance?
AB  - The diversity of human immunodeficiency virus type 1 (HIV-1) has given rise to
      multiple subtypes and recombinant strains. The majority of research into
      antiretroviral agents and drug resistance has been performed on subtype B
      viruses, yet non-subtype B strains are responsible for 90% of global infections.
      Although it seems that combination antiretroviral regimens are effective against
      all HIV-1 subtypes, there is emerging evidence of subtype differences in drug
      resistance, relevant to antiretroviral strategies in different parts of the
      world. For this purpose, extensive sampling of HIV genetic diversity, curation
      and analyses are required to inform antiretroviral strategies in different parts
      of the world.

PMID- 23006586
TI  - alr0882 encoding a hypothetical protein of Anabaena PCC7120 protects Escherichia
      coli from nutrient starvation and abiotic stresses.
AB  - This study is the first to demonstrate cloning of alr0882, a hypothetical protein
      gene of Anabaena PCC7120, its heterologous expression in Escherichia coli strain
      LN29MG1655 (?uspA::Kan) and functional complementation of abiotic stress
      tolerance of E. coli UspA. The recombinant vector pGEX-5X-2-alr0882 was used to
      transform ?uspA E. coli strain. The IPTG induced expression of a 56.6kDa GST
      fusion protein was visualized on SDS-PAGE and attested by immunoblotting. E. coli
      ?uspA strain harboring pGEX-5X-2-alr0882 when grown under carbon, nitrogen,
      phosphorus and sulphur limitation and abiotic stresses e.g. nalidixic acid,
      cycloserine, CdCl(2), H(2)O(2), UV-B, phenazine methosulphate (PMS),
      dinitrophenol (DNP), NaCl, heat, carbofuron and CuCl(2) demonstrated about 22.6
      51.6% increase in growth over the cells transformed with empty vector. Expression
      of alr0882 gene in mutant E. coli as measured by semi-quantitative RT-PCR at
      different time points under selected treatments reaffirmed its role in tolerance
      against stresses employed in this study. Thus the results of this study vividly
      demonstrated that the novel protein alr0882, although appreciably different from
      the known UspA of E. coli, offers tolerance to abiotic stresses hence holds
      potential for the development of transgenic cyanobacteria.

PMID- 23006587
TI  - Leisure-time physical activity and disability retirement: a prospective cohort
      study.
AB  - BACKGROUND: To examine whether leisure-time physical activity is associated with
      all-cause disability retirement as well as disability retirement due to
      musculoskeletal and mental causes. METHODS: The baseline data were collected by
      questionnaire surveys in 2000-2002 among 40- to 60-year-old employees of the City
      of Helsinki. Disability retirement data were derived from the registry of the
      Finnish Centre for Pensions (maximum follow-up time 6.8 years). The analysis
      included 4920 women and 1355 men. Physical activity was converted to metabolic
      equivalent (MET) index. We classified the participants into 4 groups according to
      physical activity recommendations and according to the participation in vigorous
      intensity activities. Cox regression analysis was used to calculate hazard
      ratios. RESULTS: Physical activity decreased the risk of all-cause disability
      retirement among both genders, however, women engaging in recommended volume of
      moderate-intensity activity only did not have reduced risk. Those engaging in
      vigorous activity with sufficient total volume had clearly reduced risk of
      disability retirement. The association was similar when examining disability
      retirement due to musculoskeletal and mental causes. CONCLUSION: For healthy
      middle-aged engaging in moderate-intensity physical activity additional vigorous
      exercise may be useful for maintaining musculoskeletal and mental health and thus
      lower the risk of subsequent disability retirement.

PMID- 23006588
TI  - Preparation and characterization of nanosized P(NIPAM-MBA) hydrogel particles and
      adsorption of bovine serum albumin on their surface.
AB  - Thermosensitive polymer hydrogel particles with size varying from 480 to 620 nm
      were prepared through precipitation copolymerization of N-isopropylacrylamide
      with N,N'-methylenebisacrylamide (MBA) in water with ammonium persulfate as the
      initiator. Only polymer hydrogels without any coagula were obtained when MBA
      concentration in the monomer mixture was kept between 2.5 and 10.0 wt%; with
      increased MBA concentration, the monomer conversion was enhanced, the size of the
      hydrogels was increased, and their shrinking was lessened when heated from 25
      degrees C to 40 degrees C. Bovine serum albumin adsorption on the surface of the
      hydrogels of different MBA content was measured at different pH levels and under
      different temperatures. The results demonstrated that the adsorption of the
      protein on the hydrogels could be controlled by adjusting the pH, the temperature
      of adsorption, and the crosslinking in the hydrogels. The results were
      interpreted, and the mechanisms of the polymerization were proposed.

PMID- 23006589
TI  - Induction of autophagic cell death of glioma-initiating cells by cell-penetrating
      D-isomer peptides consisting of Pas and the p53 C-terminus.
AB  - Glioblastoma multiforme (GBM) is the most aggressive and fatal brain tumor. GBM
      is resistant to chemotherapy and radiation. Recent studies have shown that glioma
      initiating cells (GICs), which have characteristics of cancer stem cells, are
      responsible for the resistance to chemotherapy and radiation and regrowth. No
      effective therapy for GICs has been developed. Here we showed that D-isomer
      peptides (dPasFHV-p53C') consisting of a cell-penetrating peptide (FHV),
      penetration accelerating sequence (Pas) and C-terminus of p53 (p53C') induced the
      cell death of GICs. dPasFHV-p53C' was effectively transduced into human GICs. The
      peptides dose-dependently inhibited cell growth and at 3 MUM completely blocked
      the growth of GICs but not embryonic stem cells. Autophagic cell death was
      observed in the GICs treated with dPasFHV-p53C' but apoptosis was not. dPasFHV
      without p53C' showed the same effect as dPasFHV-p53C', suggesting Pas to play a
      critical role in the cell death of GICs. Finally, dPasFHV-p53C' reduced tumor
      mass in mice transplanted with GICs. Peptide transduction therapy using dPasFHV
      p53C' could be a new method for the treatment of GBM.

PMID- 23006590
TI  - Prognosis after percutaneous coronary intervention in patients with psoriasis: a
      cohort study using Danish nationwide registries.
AB  - BACKGROUND: Psoriasis is an inflammatory disease associated with increased risk
      of coronary artery disease. However, the potential impact of psoriasis on the
      prognosis following percutaneous coronary revascularization (PCI) is unknown.
      METHODS: The study comprised the entire Danish population undergoing first-time
      PCI in the period 2002-09. Cox regression models, controlling for age, gender,
      socioeconomic status, pharmacological treatment, and comorbidity were used to
      assess the risk of 1) all-cause mortality and 2) a composite endpoint of death,
      myocardial infarction, and stroke. RESULTS: A total of 53,141 patients with first
      time PCI in the study period were identified. Of these, 1074 had mild psoriasis
      and 315 had severe psoriasis. Patients with severe psoriasis, but not those with
      mild disease had increased risk of both endpoints compared to patients without
      psoriasis. The incidence rates for all-cause mortality were 30.5 (CI 29.7-31.3),
      29.9 (CI 24.7-36.1), and 47.2 (CI 35.0-63.6) per 1000 patient years for patients
      without psoriasis, with mild psoriasis, and with severe psoriasis, respectively.
      Hazard ratios were 1.10 (CI 0.91-1.33) and 1.67 (CI 1.24-2.26) for mild and
      severe psoriasis, respectively. Patients with severe psoriasis were less likely
      to receive secondary prevention pharmacotherapy with betablockers, statins and
      platelet inhibitors. CONCLUSION: This first study of the prognosis following PCI
      in patients with psoriasis demonstrated an increased risk of all-cause mortality
      and of a composite of death, myocardial infarction and stroke, respectively, in
      patients with severe psoriasis compared to patients without psoriasis. Further
      studies of this novel association are needed.

PMID- 23006591
TI  - Strong perpendicular magnetocrystalline anisotropy of bulk and the (001) surface
      of DO22Mn3Ga: a density functional study.
AB  - Strong perpendicular magnetocrystalline anisotropy (MCA) and low saturation
      magnetization are found in DO22Mn(3)Ga using the full-potential linearized
      augmented plane wave (FLAPW) method. The ferrimagnetism in the bulk is well
      preserved in the surfaces of Mn(3)Ga for two possible terminations, where the
      perpendicular MCA in the (001) direction is greatly enhanced over the bulk,
      consistent with experiments. Furthermore, the robustness of MCA with respect to
      lattice strain and a good lattice match with popular substrates suggest that
      Mn(3)Ga can be a good candidate for strain-resistance spintronics applications.

PMID- 23006593
TI  - Microbiological and clinical characteristics of bacteraemia caused by the
      hypermucoviscosity phenotype of Klebsiella pneumoniae in Korea.

PMID- 23006592
TI  - Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative
      damage.
AB  - BACKGROUND: Lung allografts contain large amounts of iron (Fe), which inside lung
      macrophages may promote oxidative lysosomal membrane permeabilization (LMP), cell
      death and inflammation. The macrolide antibiotic azithromycin (AZM) accumulates
      1000-fold inside the acidic lysosomes and may interfere with the lysosomal pool
      of Fe. OBJECTIVE: Oxidative lysosomal leakage was assessed in lung macrophages
      from lung transplant recipients without or with AZM treatment and from healthy
      subjects. The efficiency of AZM to protect lysosomes and cells against oxidants
      was further assessed employing murine J774 macrophages. METHODS: Macrophages
      harvested from 8 transplant recipients (5 without and 3 with ongoing AZM
      treatment) and 7 healthy subjects, and J774 cells pre-treated with AZM, a high
      molecular-weight derivative of the Fe chelator desferrioxamine or ammonium
      chloride were oxidatively stressed. LMP, cell death, Fe, reduced glutathione
      (GSH) and H-ferritin were assessed. RESULTS: Oxidant challenged macrophages from
      transplants recipients without AZM exhibited significantly more LMP and cell
      death than macrophages from healthy subjects. Those macrophages contained
      significantly more Fe, while GSH and H-ferritin did not differ significantly.
      Although macrophages from transplant recipients treated with AZM contained both
      significantly more Fe and less GSH, which would sensitize cells to oxidants,
      these macrophages resisted oxidant challenge well. The preventive effect of AZM
      on oxidative LMP and J774 cell death was 60 to 300 times greater than the other
      drugs tested. CONCLUSIONS: AZM makes lung transplant macrophages and their
      lysososomes more resistant to oxidant challenge. Possibly, prevention of
      obliterative bronchiolitis in lung transplants by AZM is partly due to this
      action.

PMID- 23006594
TI  - Template-based combinatorial enumeration of virtual compound libraries for
      lipids.
AB  - A variety of software packages are available for the combinatorial enumeration
      of virtual libraries for small molecules, starting from specifications of core
      scaffolds with attachments points and lists of R-groups as SMILES or SD files.
      Although SD files include atomic coordinates for core scaffolds and R-groups, it
      is not possible to control 2-dimensional (2D) layout of the enumerated structures
      generated for virtual compound libraries because different packages generate
      different 2D representations for the same structure. We have developed a software
      package called LipidMapsTools for the template-based combinatorial enumeration of
      virtual compound libraries for lipids. Virtual libraries are enumerated for the
      specified lipid abbreviations using matching lists of pre-defined templates and
      chain abbreviations, instead of core scaffolds and lists of R-groups provided by
      the user. 2D structures of the enumerated lipids are drawn in a specific and
      consistent fashion adhering to the framework for representing lipid structures
      proposed by the LIPID MAPS consortium. LipidMapsTools is lightweight, relatively
      fast and contains no external dependencies. It is an open source package and
      freely available under the terms of the modified BSD license.

PMID- 23006595
TI  - Perioperative risk factors for deep vein thrombosis after total hip arthroplasty
      or total knee arthroplasty.
AB  - STUDY OBJECTIVE: To determine the perioperative frequency of deep vein thrombosis
      (DVT) after lower limb joint prosthesis surgery using Doppler ultrasonography
      (US). DESIGN: Prospective cohort study. SETTING: Operating room and hospital
      ward. PATIENTS: 144 consecutive ASA physical status 1 and 2 patients who
      underwent elective total hip arthroplasty (THA; n=64) or total knee arthroplasty
      (TKA; n= 80). INTERVENTIONS: Patients were allocated to two groups, those who
      developed DVT (DVT group) postoperatively and those who did not (no-DVT group).
      To examine the perioperative risk factors for DVT after THA or TKA, comparative
      analysis of the two groups was done. MEASUREMENTS: Doppler US was performed on
      all patients from the bilateral femoral to lower limb to detect the existence of
      DVT postoperatively. MAIN RESULTS: DVT was detected in 61 patients (42%),
      including three proximal DVT patients (2%). Preoperative elevated plasma D-dimer
      value [P = 0.0131, odds ratio (OR) 1.54, 95% CI 1.10-2.17] and history of
      hyperlipidemia (P = 0.0453, OR 6.92, 95% CI 1.04-46.00] were significant risk
      factors for the onset of DVT. A preoperative plasma D-dimer cutoff value as a
      diagnostic test was obtained as 0.85 MUg/mL. CONCLUSIONS: A high preoperative
      plasma D-dimer value and/or history of hyperlipidemia were risk factors for DVT
      after THA or TKA.

PMID- 23006596
TI  - Anesthetic management during labor and delivery: a 21-year review of women with
      cancer in a tertiary care center.
AB  - STUDY OBJECTIVE: To describe the anesthetic management of labor and delivery in
      patients presenting with cancer during pregnancy at one institution. DESIGN:
      Retrospective data collection of pregnant cancer patients who delivered between
      January 1988 and December 2009. SETTING: University-affiliated teaching hospital.
      MEASUREMENTS: Clinical data on cancer diagnosis and treatment and obstetric,
      neonatal, and anesthetic management of the study patients were compiled. Analysis
      was done based on whether the cancer was diagnosed before or during pregnancy.
      MAIN RESULTS: The incidence of cancer during pregnancy at our institution was
      0.1%. No difference was noted in the incidence of cancer diagnosed before and
      during pregnancy was noted. Women with a cancer diagnosis during pregnancy had
      more clinical symptoms, a higher rate of inductions (37% vs 11%; P = 0.0002) and
      premature deliveries (48% vs 20%; P = 0.0003) than those with a cancer diagnosis
      before delivery. No differences between groups in neonatal outcome were noted.
      Most patients received regional anesthesia for labor and delivery (75%); a
      significant number (22%) also received general anesthesia for cesarean section.
      Life-threatening complications were seen in those with mediastinal tumors or
      metastases. CONCLUSION: Women with cancer diagnosed during pregnancy are likely
      to require prompt therapeutic intervention and have a potential for premature
      delivery. Anesthetic management should be tailored to the individual type of
      cancer, depending on the severity of symptoms, stage of cancer, and associated
      systemic involvement.

PMID- 23006597
TI  - Cancer and pregnancy: a difficult combination requiring multidisciplinary care.

PMID- 23006599
TI  - Rab11-family of interacting protein 2 associates with chlamydial inclusions
      through its Rab-binding domain and promotes bacterial multiplication.
AB  - Chlamydia trachomatis, an obligate intracellular pathogen, survives within host
      cells in a special compartment named 'inclusion' and takes advantage of host
      vesicular transport pathways for its growth and replication. Rab GTPases are key
      regulatory proteins of intracellular trafficking. Several Rabs, among them Rab11
      and Rab14, are implicated in chlamydial development. FIP2, a member of the Rab11
      Family of Interacting Proteins, presents at the C-terminus a Rab-binding domain
      that interacts with both Rab11 and Rab14. In this study, we determined and
      characterized the recruitment of endogenous and GFP-tagged FIP2 to the chlamydial
      inclusions. The recruitment of FIP2 is specific since other members of the Rab11
      Family of Interacting Proteins do not associate with the chlamydial inclusions.
      The Rab-binding domain of FIP2 is essential for its association. Our results
      indicate that FIP2 binds to Rab11 at the chlamydial inclusion membrane through
      its Rab-binding domain. The presence of FIP2 at the chlamydial inclusion favours
      the recruitment of Rab14. Furthermore, our results show that FIP2 promotes
      inclusion development and bacterial replication. In agreement, the silencing of
      FIP2 decreases the bacterial progeny. C. trachomatis likely recruits FIP2 to
      hijack host intracellular trafficking to redirect vesicles full of nutrients
      towards the inclusion.

PMID- 23006598
TI  - Is there an advantage to delivering breast boost in the lateral decubitus
      position?
AB  - BACKGROUND: The purpose of this study was to compare the change in depth of
      target volume and dosimetric parameters between the supine and lateral decubitus
      positions for breast boost treatment with electron beam therapy. METHODS: We
      analyzed 45 patients who were treated, between 2009-2010, with whole breast
      radiation (WBRT) followed by a tumor bed boost in the lateral decubitius
      position. Tumor bed volume, distance from skin to the maximal depth of the tumor
      bed, D90 (dose covering 90% of the tumor bed volume), maximal dose, electron
      energy and doses to heart and lungs were compared. Additional variables of body
      mass index (BMI) and tumor bed location were also analyzed to see if there was a
      benefit limited to any subgroup. RESULTS: Median BMI for the 45 patients treated
      was 30.6 (20.6-42.4). When comparing the supine scan to the lateral decubitus
      scan, there was no significant difference in the tumor bed volume (p = 0.116).
      There was a significant difference between depth to the tumor bed in the supine
      scan and lateral decubitus scan (p < 0.001). The mean maximum doses and D90
      between the two scans were 110.7 (100.0-133.0)% vs 106.1 (95.1-116.9)% (p < 0.05)
      and 93.9 (81.3-01.0-101.0)% vs. 98.2 (89.1-108.0)% (p = 0.004) respectively.
      There was no difference in dose delivered to the lungs or heart between the two
      scans (p = 0.848 and p = 0.992 respectively). On subset analysis, there was a
      difference in depth to tumor that was seen across all BMI classes, including
      normal (p <= 0.001, overweight (p <= 0.001) and obese (p <= 0.001). The majority
      of patients had a tumor in the upper outer quadrant (77.8%) and on subset
      analysis, there was a significant difference in tumor bed volume (p < 0.01),
      depth to tumor (p < 0.01), tumor bed coverage [D90] (p < 0.05), maximum dose (p <
      0.05) and energy (p < 0.001) for this location. CONCLUSIONS: Delivering a tumor
      bed boost in the lateral decubitus position reduces the distance to the tumor bed
      allowing for a lower energy treatment to be used to treat breast cancer. It
      improves coverage and decreases maximal dose to the target volume, all of which
      would help reduce skin morbidities and should be considered for patients with
      upper outer quadrant disease, irrespective of BMI status.

PMID- 23006600
TI  - Diffusion tensor imaging predicts long-term motor functional outcome in patients
      with acute supratentorial intracranial hemorrhage.
AB  - BACKGROUND/AIM: It remains unclear how wallerian degeneration of the pyramidal
      tract (PT) in the acute phase of supratentorial intracranial hemorrhage (ICH)
      correlates with the long-term functional outcome. The aim of this study was to
      quantify and predict the long-term neuromotor outcome using diffusion tensor
      imaging (DTI) during the early stages of ICH. METHODS: Twenty-seven patients with
      a hemiparetic ICH were prospectively studied using DTI either within 3 days or at
      2 weeks after onset. A region-of-interest-based analysis was performed for
      fractional anisotropy (FA) of the PT in the cerebral peduncle. The degree of
      paresis was assessed upon admission and at 6 months using paresis grading (PG),
      and the functional outcome was evaluated using the modified Rankin Scale (mRS).
      The activities of daily living were evaluated using the Functional Independence
      Measure (FIM). RESULTS: The FA values within 3 days and after 2 weeks of ICH
      onset were significantly decreased at the affected side (p = 0.001, reduced by
      11%; p < 0.001, reduced by 14%, respectively), but the mean diffusivity at the
      same time points remained unchanged (p = 0.05 and p = 0.136, respectively). The
      ratio of the FA (rFA) at the affected side to that of the unaffected side within
      3 days was negatively correlated with the PG (p < 0.001, r = -0.642), positively
      correlated with the FIM scores (p = 0.004, r = 0.532), and negatively correlated
      with the mRS scores at the end of follow-up (median = 17 months) (p = 0.010, r = 
      0.490). The rFA at 2 weeks was positively correlated with the FIM (p < 0.001, r =
      0.661) and negatively correlated with mRS scores and PG at the end of follow-up
      (p < 0.001, r = -0.653; p < 0.001, r = -0.700). For both patients with good and
      poor outcomes based on the PG, the area under the receiver operating
      characteristic (ROC) curve for rFA at 2 weeks was greater than the area under the
      ROC for rFA within 3 days, and the cutoff point for the rFA at 2 weeks was set at
      0.875 (sensitivity 76%, specificity 89%). CONCLUSIONS: This study demonstrated
      that the use of DTI during the early stages of ICH may predict motor outcomes at
      6 months after ICH. Moreover, as compared to use of DTI within 3 days of ICH
      onset, the application of DTI at 2 weeks after ICH could more accurately predict
      the motor outcomes and daily living activities of patients.

PMID- 23006602
TI  - Obstructive sleep apnea and multimorbidity.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is becoming increasingly prevalent in
      North America and has been described in association with specific chronic
      diseases, particularly cardiovascular diseases. In primary care, where the
      prevalence of co-occurring chronic conditions is very high, the potential
      association with OSA is unknown. The purpose of this study was to explore the
      association between OSA and 1) the presence and severity of multimorbidity
      (multiple co-occurring chronic conditions), and 2) subcategories of
      multimorbidity. METHODS: A cluster sampling technique was used to recruit 120
      patients presenting with OSA of various severities from the records of a sleep
      laboratory in 2008. Severity of OSA was based on the results of the
      polysomnography. Patients invited to participate received a mail questionnaire
      including questions on sociodemographic characteristics and the Disease Burden
      Morbidity Assessment (DBMA). They also consented to give access to their medical
      records. The DBMA was used to provide an overall multimorbidity score and sub
      score of diseases affecting various systems. RESULTS: Bivariate analysis did not
      demonstrate an association between OSA and multimorbidity (r = 0.117; p = 0.205).
      However, severe OSA was associated with multimorbidity (adjusted odds ratio =
      7.33 [1.67-32.23], p = 0.05). OSA was moderately correlated with vascular (r =
      0.26, p = 0.01) and metabolic syndrome (r = 0.26, p = 0.01) multimorbidity sub
      scores. CONCLUSIONS: This study showed that severe OSA is associated with severe
      multimorbidity and sub-scores of multimorbidity. These results do not allow any
      causal inference. More research is required to confirm these associations.
      However, primary care providers should be aware of these potential associations
      and investigate OSA when deemed appropriate.

PMID- 23006603
TI  - Structure-guided design, synthesis and biological evaluation of novel DNA ligase
      inhibitors with in vitro and in vivo anti-staphylococcal activity.
AB  - A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent
      inhibition of bacterial NAD(+)-dependent DNA ligases (LigAs) evolved from a 2,4
      diaminopteridine derivative discovered by HTS. The design was guided by several
      highly resolved X-ray structures of our inhibitors in complex with either
      Streptococcus pneumoniae or Escherichia coli LigA. The structure-activity
      relationship based on the ANC scaffold is discussed. The in-depth
      characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3
      carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1
      mg/L) and in vivo anti-staphylococcal activity, is presented.

PMID- 23006604
TI  - How hydrogen bonds impact P-glycoprotein transport and permeability.
AB  - The requirement to cross a biological membrane can be a complex process
      especially if multidrug transporters such as P-gp must be considered. Drug
      partitioning into the lipid membrane and efflux by P-gp are tightly coupled
      processes wherein H-bonding interactions play a key role. All H-bond donors and
      acceptors are not equal in terms of the strength of the H-bonds that they form,
      hence it is important to consider their relative strength. Using various examples
      from literature, we illustrate the benefits of considering the relative strengths
      of individual H-bonds and introducing intramolecular H-bonds to increase membrane
      permeability and/or decrease P-gp efflux.

PMID- 23006605
TI  - Management of diabetes in Guinean traditional medicine: an ethnobotanical
      investigation in the coastal lowlands.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This survey was carried out in the coastal
      lowlands of Guinea-Conakry in order to make an inventory of plants used by
      traditional healers, herbalists and diabetic patients for the management of
      diabetes mellitus. MATERIALS AND METHODS: Frequent ethnomedical and
      ethnobotanical investigations were conducted from June 2008 to December 2009 in
      Conakry, Kindia, Forecariah, Dubreka, Boke, Fria and Boffa. It is a cross
      sectional survey and data collection is based on the interactive method. During
      this period a total of 112 people aged from 39 to 76 years old were interviewed.
      RESULTS: During this investigation 146 plant species belonging to 55 families
      were collected. The most cited plants were Anacardium occidentale L. and Ficus
      spp., while the Fabaceae family was the most represented, followed by the
      Euphorbiaceae and Rubiaceae. The most frequently plant parts used by the
      traditional healers and the herbalists were the stem-bark and decoctions the most
      common preparation mode. CONCLUSIONS: It is clear that a variety of plants is
      used in the management and treatment of diabetes. Due to the increasing
      prevalence of type 2 diabetes, there is an urgent need for scientific
      investigations to rationalise the use of these traditional remedies, which could
      represent accessible alternative medicines for the Guinean populations.

PMID- 23006606
TI  - Recreational physical activity in postmenopausal women is stable over 8 years of
      follow-up.
AB  - BACKGROUND: The goals of this study were to examine 1) longitudinal trajectories
      of energy expenditure from recreational physical activity (PA) in postmenopausal
      women, 2) whether women who belong to different PA trajectories engage in
      different types of PA, and 3) whether baseline sociodemographic, health,
      psychosocial, and lifestyle characteristics predict membership in PA
      trajectories. METHODS: Women from the Women's Health Initiative Observational
      Study with baseline PA data (n = 92,629) were included. Physical activity,
      measured via self-report 6 times over 8 years, was converted to MET hr/wk for
      analysis. Latent growth curve mixture models and latent profile models were used
      to analyze longitudinal PA trajectories and cross-sectional PA composition,
      respectively. RESULTS: Three distinct, stable PA trajectories (highly,
      moderately, and minimally active) were identified with nearly 75% of the women
      classified as minimally active (<= 8 MET-hr/wk). The majority of women who were
      at least moderately active engaged in a balanced combination of walking,
      moderate, and vigorous PA. Sociodemographic characteristics such as income,
      education, and past vigorous PA were predictive of PA trajectory, as were some
      health status indicators (eg, body mass index), but not health related quality of
      life. CONCLUSIONS: Self-reported PA is largely stable across nearly a decade of
      follow-up in postmenopausal women.

PMID- 23006608
TI  - Left ventricular hydatid cyst: an uncommon cause of chest pain in young adults.
AB  - Isolated cardiac involvement in hydatid disease is very rare. We report the case
      of a young adult male who presented to the emergency department with acute onset
      of chest pain and was surprisingly detected to have a hydatid cyst in the left
      ventricular myocardium. The transthoracic echocardiography and cardiac magnetic
      resonance imaging confirmed the diagnosis. Cardiac hydatid disease should be
      considered in the differential diagnosis of chest pain in young individuals in
      the absence of conventional risk factors of atherosclerosis.

PMID- 23006607
TI  - Morbidity and mortality of nonagenarians undergoing CoreValve implantation.
AB  - BACKGROUND: Nonagenarians are mostly denied from different therapeutic strategies
      due to high comorbidity index and risk-benefit calculation. We present the
      results of nonagenarians with high comorbidity index not eligible for
      conventional aortic valve surgery undergoing transcatheter aortic valve
      implantation (TAVI) with the CoreValve system. METHODS: Our retrospective
      analysis include baseline parameters, procedural characteristics, morbidity,
      mortality as well as twelve-lead surface ECG and echocardiographic parameters
      which were revealed preinterventionally, at hospital discharge and at 30-day
      follow-up. Clinical follow-up was performed 6 months after TAVI. RESULTS: Out of
      158 patients 11 nonagenarians with a mean age of 92.6 +/- 1.3 years suffering
      from severe aortic valve stenosis and elevated comorbidity index (logistic
      EuroSCORE of 32.0 +/- 9.5%, STS score 25.3 +/- 9.7%) underwent TAVI between
      January 2008 and January 2011 using the third-generation percutaneous self
      expanding CoreValve prosthesis. Baseline transthoracic echocardiography reported
      a mean aortic valve area (AVA) of 0.6 +/- 0.2 cm(2) with a mean and peak pressure
      gradient of 60.2 +/- 13.1 mmHg and 91.0 +/- 27.4 mmHg, respectively. The 30-day
      follow up all cause and cardiovascular mortality was 27.3% and 9.1%,
      respectively. One major stroke (9.1%), 2 pulmonary embolisms (18.2%), 1
      periprocedural (9.1%) and 1 (9.1%) spontaneous myocardial infarction occured.
      Life-threatening or disabling bleeding occurred in 2 cases (18.2%), and minor
      bleeding in 7 cases (63.6%). Mean severity of heart failure according to NYHA
      functional class improved from 3.2 +/- 0.8 to 1.36 +/- 0.5 while mean AVA
      increased from 0.6 +/- 0.2 cm(2) to 1.8 +/- 0.2 cm(2). At 6-months follow-up 8
      patients (72.7%) were alive without any additional myocardial infarction,
      pulmonary embolism, bleeding, or stroke as compared to 30-day follow-up.
      CONCLUSION: Our case series demonstrate that even with elevated comorbidity
      index, clinical endpoints and valve-associated results are relatively favorable
      in nonagenarians treated with CoreValve.

PMID- 23006609
TI  - Efficacy of confocal laser endomicroscopy for discriminating colorectal neoplasms
      from non-neoplasms: a systematic review and meta-analysis.
AB  - AIM: Confocal laser endomicroscopy (CLE) has evolved to allow in vivo real-time
      biopsy for the classification of colorectal lesions. The primary aim of this
      study was to assess the effectiveness of CLE for discriminating colorectal
      neoplasms from non-neoplasms and its contributing factors. The secondary aim was
      to compare the efficacy of endomicroscopy and chromoendoscopy for diagnosing
      colorectal neoplasms. METHOD: A systematic review of the literature published
      between 2000 and 2012 was conducted. Pooled sensitivity and specificity were
      compared using univariate regression analysis according to prespecified
      subgroups. Pooled relative risk was computed to compare the accuracy of
      endomicroscopy and chromoendoscopy. RESULTS: Fifteen studies involving 719
      patients and 2290 specimens were analysed. The pooled sensitivity of all studies
      was 0.94 [95% confidence intervals (CI): 0.88-0.97], and pooled specificity was
      0.95 (95% CI: 0.89-0.97). Real-time CLE yielded higher sensitivity (0.96 vs 0.85,
      P < 0.001) and specificity (0.97 vs 0.82, P < 0.001) than blinded CLE. For real
      time CLE, endoscopy-based systems had better sensitivity (0.96 vs 0.89, P <
      0.001) and specificity (0.99 vs 0.82, P < 0.0001) than probe-based systems. CLE
      yielded equivalent accuracy compared with magnifying virtual chromoendoscopy and
      magnifying pigment chromoendoscopy (P > 0.05). CONCLUSION: CLE is comparable to
      colonoscopic histopathology in diagnosing colorectal neoplasms, and is better in
      conjunction with conventional endoscopy. An endoscopy-based rather than a probe
      based modality would be optimal in the application of CLE.

PMID- 23006610
TI  - Contemporary outcomes of optimally treated heart failure patients with sleep
      apnea. Case for urgency in evaluation of newer interventions? From the Atlanta
      Cardiomyopathy Consortium.

PMID- 23006611
TI  - Ferrous ferric chloride downregulates the inflammatory response to Rhodococcus
      aurantiacus infection in mice.
AB  - The healthy drink Pairogen is mainly composed of ferrous ferric chloride water
      that reportedly changes the status of intracellular water from oxidative to
      antioxidative. Here, we investigated whether Pairogen affects host immune
      function in a murine model of granulomatous inflammation in response to
      Rhodococcus aurantiacus (R. aurantiacus) infection. Longitudinal ingestion of
      Pairogen markedly improved the survival of infected mice in a concentration
      dependent manner. Compared to mice received water, mice that ingested 10-fold
      diluted Pairogen displayed rapid bacterial elimination, decreased production of
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and high levels of IL
      10 in organs during the initial phase of infection. Moreover, histological
      studies showed significant reduction in the number and size of granulomas as well
      as amelioration of oxidative stress in the livers of mice ingested 10-fold
      diluted Pairogen at 14 d post-infection. These characteristics were further
      pronounced in first-generation (F1) mice that also ingested 10-fold-diluted
      Pairogen. Following stimulation with heat-killed R. aurantiacus, the production
      of TNF-alpha, IL-6, and IL-10 by macrophages from F1 mice was similar to that
      detected in vivo, while their gene expression levels in these cells were
      significantly lower than the levels in macrophages from mice received water. Heat
      killed R. aurantiacus also induced the expression of heme oxygenase-1 mRNA in the
      cells from F1 mice. Taken together, these results indicate that Pairogen
      contributes to the negative regulation of the immuno-inflammatory response to R.
      aurantiacus infection in mice by modulating the cellular redox state.
      Longitudinal ingestion of Pairogen further enhances the defense function in mouse
      progeny.

PMID- 23006612
TI  - Constructing perfect phylogenies and proper triangulations for three-state
      characters.
AB  - : In this paper, we study the problem of constructing perfect phylogenies for
      three-state characters. Our work builds on two recent results. The first result
      states that for three-state characters, the local condition of examining all
      subsets of three characters is sufficient to determine the global property of
      admitting a perfect phylogeny. The second result applies tools from minimal
      triangulation theory to the partition intersection graph to determine if a
      perfect phylogeny exists. Despite the wealth of combinatorial tools and
      algorithms stemming from the chordal graph and minimal triangulation literature,
      it is unclear how to use such approaches to efficiently construct a perfect
      phylogeny for three-state characters when the data admits one. We utilize
      structural properties of both the partition intersection graph and the original
      data in order to achieve a competitive time bound.

PMID- 23006614
TI  - Influence of spatial neglect, hemianopia and hemispace on the subjective
      vertical.
AB  - The perception of the vertical is frequently shifted to the contralesional side
      in patients with hemispheric lesions, and this is amplified by spatial neglect.
      However, we do not know the specific influence of hemianopia and space of
      perception on this phenomenon. Here, we analyzed the respective influences of
      spatial neglect, hemianopia and hemispace on the subjective vertical in patients
      with right hemispheric stroke. Twelve neglect patients with and 5 without
      hemianopia were compared to 3 non-neglect patients with and 13 without
      hemianopia. They had to match a luminous rod to the vertical, either in the mid
      sagittal plane or in the right or the left hemispace. Patients showed a counter
      clockwise deviation, and this was exaggerated by both neglect and hemianopia. In
      patients with neglect, the error was greater in the left hemispace. In
      conclusion, neglect and hemianopia had additive effects on the contralesional
      bias of the subjective vertical.

PMID- 23006613
TI  - Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of
      a randomized trial.
AB  - RATIONALE: Pulmonary rehabilitation is an important treatment for patients with
      Chronic Obstructive Pulmonary Disease, who are often vitamin D deficient. As
      vitamin D status is linked to skeletal muscle function, we aimed to explore if
      high dose vitamin D supplementation can improve the outcomes of rehabilitation in
      Chronic Obstructive Pulmonary Disease. MATERIAL AND METHODS: This study is a post
      hoc subgroup analysis of a larger randomized trial comparing a monthly dose of
      100.000 IU of vitamin D with placebo to reduce exacerbations. 50 Subjects who
      followed a rehabilitation program during the trial are included in this analysis.
      We report changes from baseline in muscle strength and exercise performance
      between both study arms after 3 months of rehabilitation. RESULTS: Vitamin D
      intervention resulted in significantly higher median vitamin D levels compared to
      placebo (51 [44-62] ng/ml vs 15 [13-30] ng/ml; p < 0.001). Patients receiving
      vitamin D had significantly larger improvements in inspiratory muscle strength (
      11+/-12 cmH2O vs 0+/-14 cmH2O; p = 0.004) and maximal oxygen uptake (110+/-211
      ml/min vs -20+/-187 ml/min; p = 0.029). Improvements in quadriceps strength (15+/
      16 Nm) or six minutes walking distance (40+/-55 meter) were not significantly
      different from the effects in the placebo group (7+/-19 Nm and 11+/-74 meter;
      p>0.050). CONCLUSION: High dose vitamin D supplementation during rehabilitation
      may have mild additional benefits to training.

PMID- 23006615
TI  - The magnon dynamics and spin exchange parameters of FePS3.
AB  - The spin waves in a powdered sample of a quasi-two-dimensional antiferromagnet,
      FePS(3), have been measured using neutron inelastic scattering. The data could be
      modelled and the exchange interactions determined using a two-dimensional
      Heisenberg Hamiltonian with single ion anisotropy. A suitable fit to the data
      could only be achieved by including magnetic interactions up to the third nearest
      neighbour, which is consistent with the findings for other members of the MPS(3)
      family (M=transition metal). The best fit parameters at 6 K were J(1) = 1.49 meV,
      J(2) = 0.04 meV, J(3) =- 0.6 meV, with an anisotropy of Delta = 3.7 meV.
      Measurements as a function of temperature give a coarse measure of the behaviour
      of the anisotropy and the nature of the phase transition.

PMID- 23006616
TI  - Technical and clinical analysis of microEEG: a miniature wireless EEG device
      designed to record high-quality EEG in the emergency department.
AB  - BACKGROUND: We describe and characterize the performance of microEEG compared to
      that of a commercially available and widely used clinical EEG machine. microEEG
      is a portable, battery-operated, wireless EEG device, developed by Bio-Signal
      Group to overcome the obstacles to routine use of EEG in emergency departments
      (EDs). METHODS: The microEEG was used to obtain EEGs from healthy volunteers in
      the EEG laboratory and ED. The standard system was used to obtain EEGs from
      healthy volunteers in the EEG laboratory, and studies recorded from patients in
      the ED or ICU were also used for comparison. In one experiment, a signal splitter
      was used to record simultaneous microEEG and standard EEG from the same
      electrodes. RESULTS: EEG signal analysis techniques indicated good agreement
      between microEEG and the standard system in 66 EEGs recorded in the EEG
      laboratory and the ED. In the simultaneous recording the microEEG and standard
      system signals differed only in a smaller amount of 60 Hz noise in the microEEG
      signal. In a blinded review by a board-certified clinical neurophysiologist,
      differences in technical quality or interpretability were insignificant between
      standard recordings in the EEG laboratory and microEEG recordings from standard
      or electrode cap electrodes in the ED or EEG laboratory. The microEEG data
      recording characteristics such as analog-to-digital conversion resolution (16
      bits), input impedance (>100MOmega), and common-mode rejection ratio (85 dB) are
      similar to those of commercially available systems, although the microEEG is many
      times smaller (88 g and 9.4 * 4.4 * 3.8 cm). CONCLUSIONS: Our results suggest
      that the technical qualities of microEEG are non-inferior to a standard
      commercially available EEG recording device. EEG in the ED is an unmet medical
      need due to space and time constraints, high levels of ambient electrical noise,
      and the cost of 24/7 EEG technologist availability. This study suggests that
      using microEEG with an electrode cap that can be applied easily and quickly can
      surmount these obstacles without compromising technical quality.

PMID- 23006617
TI  - A novel exonic GHR splicing mutation (c.784G > C) in a patient with classical
      growth hormone insensitivity syndrome.
AB  - CONTEXT: Undetectable circulating growth hormone-binding protein (GHBP) can be
      indicative of a GH receptor (GHR) defect and cause GH insensitivity (GHI)
      syndrome. CASE REPORT: The proband, severely growth retarded from birth, had a
      height of 73 cm (-6 SDS) and weight of 10.5 kg (-2.5 SDS) at the age of 3.25
      years; her consanguineous parents were normal statured. Basal serum GH
      measurement was high, >40 ng/ml, while serum insulin-like growth factor-I (IGF-I;
      8.5 ng/ml; normal, 13-100), IGF-binding protein 3 (126 ng/ml; normal, 365-1,294),
      acid labile subunit (0.59 mg/l; normal, 5.6-16), and GHBP (120 pmol/l; normal,
      431-1,892) concentrations were all markedly low. Recombinant IGF-I therapy
      improved height to -4.4 SDS after 2.5 years of treatment. RESULTS: GHR gene
      analysis revealed a homozygous c.784G>C transversion, the last nucleotide of exon
      7; the parents were heterozygous for the mutation. Evaluation of GHR mRNA
      indicated c.784G>C was not a missense mutation but induced exon 7 excision,
      leading to a frame shift and predicted early protein termination. CONCLUSION: A
      novel homozygous GHRc.784G>C mutation, identified in a GHI patient, induced
      functional loss of the native intron 7 donor splice site, demonstrating, for the
      first time, the importance of exonic nucleotides at exon-intron junctions for
      normal GHR splicing.

PMID- 23006618
TI  - Large size self-assembled quantum rings: quantum size effect and modulation on
      the surface diffusion.
AB  - We demonstrate experimentally the submicron size self-assembled (SA) GaAs
      quantum rings (QRs) by quantum size effect (QSE). An ultrathin In0.1 Ga0.9As
      layer with different thickness is deposited on the GaAs to modulate the surface
      nucleus diffusion barrier, and then the SA QRs are grown. It is found that the
      density of QRs is affected significantly by the thickness of inserted In0.1
      Ga0.9As, and the diffusion barrier modulation reflects mainly on the first five
      monolayer . The physical mechanism behind is discussed. The further analysis
      shows that about 160 meV decrease in diffusion barrier can be achieved, which
      allows the SA QRs with density of as low as one QR per 6 MUm2. Finally, the QRs
      with diameters of 438 nm and outer diameters of 736 nm are fabricated using QSE.

PMID- 23006619
TI  - Toward defining the regenerative potential of olfactory mucosa: establishment of
      Schwann cell-free adult canine olfactory ensheathing cell preparations suitable
      for transplantation.
AB  - Olfactory mucosa (OM)-derived olfactory ensheathing cells (OECs) are attractive
      candidates for autologous cell transplantation-based therapy of nervous system
      injury. However, defining the regenerative capacity of OM-derived OECs is impeded
      by the fact that cell cultures used for transplantation  may contain significant
      amounts of contaminating trigeminal nerve Schwann cells that escape
      identification by sharing in vitro expression of OEC markers. The aim of the
      present study, therefore, was to quantify contaminating Schwann cells in OEC
      preparations and to develop a protocol for their  specific depletion. Based on
      the observation that freshly dissociated, but not cultured, OECs and Schwann
      cells display differential expression of HNK-1 and p75(NTR), magnet-activated
      cell sorting (MACS) was used to deplete myelinating (HNK-1-positive) and
      nonmyelinating (p75(NTR)-positive)  Schwann cells from primary cell suspensions
      containing HNK-1-/p75(NTR)-negative OECs. Upregulation of p75(NTR) expression in
      OECs during culturing allowed their subsequent MACS-based separation from
      fibroblasts. Immunofluorescence analysis of freshly dissociated OM prior  to MACS
      depletion revealed that 21% of the total and 56% of all CNPase-positive cells,
      representing both OECs and Schwann cells, expressed the Schwann cell antigens HNK
      1 or p75(NTR), indicating that freshly dissociated OM prior to culturing
      contained as many Schwann cells as OECs,  while olfactory bulb (OB) primary cell
      suspensions revealed lower levels of Schwann cell contamination. Interestingly,
      neurite growth of neonatal rat dorsal root ganglion (DRG) neurons cocultured with
      OM-OECs, OB-OECs, and fibular nerve (FN) Schwann cells used as control was
      significantly  higher in the presence of OECs than of Schwann cells. The first
      report on identification and specific depletion of Schwann cells from OEC
      preparations provides a solid basis for future efforts to fully define the
      regenerative potential of nasal mucosa OECs.

PMID- 23006622
TI  - Change in cortical vessel signs on susceptibility-weighted images after full
      recanalization in hyperacute ischemic stroke.
AB  - BACKGROUND: The cortical vessel signs (CVSs) on susceptibility-weighted images
      (SWIs) have been reported in patients with hyperacute ischemic stroke. We
      evaluated the change of this susceptibility sign on the immediate SWI after full
      recanalization and its clinical implications. METHODS: Nineteen hyperacute
      ischemic stroke patients who had acute large artery occlusion and underwent post
      recanalization SWI were enrolled in this study. The patients had ICA (internal
      carotid artery, 2 cases), M1 (M1 segment of middle cerebral artery, 7 cases), M2
      (M2 segment of middle cerebral artery, 1 cases), T (intracranial ICA bifurcation,
      2 cases), ICA/M1 (4 cases) and basilar artery (3 cases) occlusion on imaging
      studies before thrombolysis and they underwent immediate magnetic resonance
      imaging, including the SWI, after full recanalization. The recanalization status
      was evaluated using the thrombolysis in cerebral infarction (TICI) score before
      and after thrombolysis. The SWI images were evaluated for the presence of
      asymmetry of veins over the ischemic territory and this was correlated with the
      site of stenosis or occlusion. The veins in the ischemic territory were
      classified as 'prominent' if there were more numerous veins and/or large veins
      with a greater signal loss observed compared with the opposite normal hemisphere,
      'equal' if there were no significant difference in appearance in both the
      cerebral hemispheres, and 'less' if the veins were decreased in the affected area
      as compared with that of the normal cortex. Baseline clinical parameters and
      clinical outcomes were reviewed. RESULTS: The initial TICI grades were 0 in all
      cases. After thrombolysis, TICI grades were 3 in all cases. The pre
      recanalization SWIs were obtained in 10 of 19 patients and all 10 showed
      prominent CVSs over the affected side, which disappeared on the post
      recanalization SWI. On the post-recanalization SWI, the observed veins in the
      affected area were equal (10/19), less (5/19), and both equal and less (4/19).
      Patients with equal cortical veins in the affected area had small lesions on
      diffusion-weighted image (DWI) (10/19), while patients with less cortical veins
      had medium to large lesions on DWI (9/19). CONCLUSION: The prominent CVSs on SWI
      can be indicative of acute thromboembolic occlusion and its change immediately
      after recanalization can be used to reflect the metabolic status. After
      recanalization, the appearance of the equal CVS (return to normal) on SWI was
      associated with a favorable clinical outcome and infarction was avoided in our
      small series study.

PMID- 23006623
TI  - TRBP alters human precursor microRNA processing in vitro.
AB  - MicroRNAs play central roles in controlling gene expression in human cells.
      Sequencing data show that many miRNAs are produced at different levels and as
      multiple isoforms that can vary in length at their 5' or 3' ends, but the
      biogenesis and functional significance of these RNAs are largely unknown. We show
      here that the human trans-activation response (TAR) RNA binding protein (TRBP), a
      known molecular partner of the miRNA processing enzyme Dicer, changes the rates
      of pre-miRNA cleavage in an RNA-structure-specific manner. Furthermore, TRBP can
      trigger the generation of iso-miRNAs (isomiRs) that are longer than the canonical
      sequence by one nucleotide. We show that this change in miRNA processing site can
      alter guide strand selection, resulting in preferential silencing of a different
      mRNA target. These results implicate TRBP as a key regulator of miRNA processing
      and targeting in humans.

PMID- 23006624
TI  - A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular
      exoribonuclease XRN1 and alters host mRNA stability.
AB  - All arthropod-borne flaviviruses generate a short noncoding RNA (sfRNA) from the
      viral 3' untranslated region during infection due to stalling of the cellular 5'
      to-3' exonuclease XRN1. We show here that formation of sfRNA also inhibits XRN1
      activity. Cells infected with Dengue or Kunjin viruses accumulate uncapped mRNAs,
      decay intermediates normally targeted by XRN1. XRN1 repression also resulted in
      the increased overall stability of cellular mRNAs in flavivirus-infected cells.
      Importantly, a mutant Kunjin virus that cannot form sfRNA but replicates to
      normal levels failed to affect host mRNA stability or XRN1 activity. Expression
      of sfRNA in the absence of viral infection demonstrated that sfRNA formation was
      directly responsible for the stabilization of cellular mRNAs. Finally, numerous
      cellular mRNAs were differentially expressed in an sfRNA-dependent fashion in a
      Kunjin virus infection. We conclude that flaviviruses incapacitate XRN1 during
      infection and dysregulate host mRNA stability as a result of sfRNA formation.

PMID- 23006626
TI  - Association of gastrointestinal distress in ultramarathoners with race diet.
AB  - CONTEXT: Gastrointestinal (GI) distress is common during ultrarunning. PURPOSE:
      To determine if race diet is related to GI distress in a 161-km ultramarathon.
      METHODS: Fifteen (10 male, 5 female) consenting runners in the Javelina Jundred
      (6.5 loops on a desert trail) participated. Body mass was measured immediately
      prerace and after each loop. Runners reported if they had nausea, vomiting,
      abdominal cramps, and/or diarrhea after each loop. Subjects were interviewed
      after each loop to record food, fluid, and electrolyte consumption. Race diets
      were analyzed using Nutritionist Pro. RESULTS: Nine (8 male, 1 female) of 15
      runners experienced GI distress including nausea (89%), abdominal cramps (44%),
      diarrhea (44%), and vomiting (22%). Fluid consumption rate was higher (p = .001)
      in runners without GI distress (10.9 +/- 3.2 ml . kg-1 . hr-1) than in those with
      GI distress (5.9 +/- 1.6 ml . kg-1 . hr-1). Runners without GI distress consumed
      a higher percentage fat (p = .03) than runners with GI distress (16.5 +/- 2.6 vs.
      11.1 +/- 5.0). In addition, fat intake rate was higher (p = .01) in runners
      without GI distress (0.06 +/- 0.03 g . kg-1 . hr-1) than in runners with GI
      distress (0.03 +/- 0.01 g . kg-1 .hr-1). Lower fluid and fat intake rates were
      evident in those developing GI distress before the onset of symptoms.
      CONCLUSIONS: A race diet with higher percentage fat and higher intake rates of
      fat and fluid may protect ultramarathoners from GI distress. However, these
      associations do not indicate cause and effect, and factors other than race diet
      may have contributed to GI distress.

PMID- 23006625
TI  - Cas5d processes pre-crRNA and is a member of a larger family of CRISPR RNA
      endonucleases.
AB  - Small RNAs derived from clustered, regularly interspaced, short palindromic
      repeat (CRISPR) loci in bacteria and archaea are involved in an adaptable and
      heritable gene-silencing pathway. Resistance to invasive genetic material is
      conferred by the incorporation of short DNA sequences derived from this material
      into the genome as CRISPR spacer elements separated by short repeat sequences.
      Processing of long primary transcripts (pre-crRNAs) containing these repeats by a
      CRISPR-associated (Cas) RNA endonuclease generates the mature effector RNAs that
      target foreign nucleic acid for degradation. Here we describe functional studies
      of a Cas5d ortholog, and high-resolution structural studies of a second Cas5d
      family member, demonstrating that Cas5d is a sequence-specific RNA endonuclease
      that cleaves CRISPR repeats and is thus responsible for processing of pre-crRNA.
      Analysis of the structural homology of Cas5d with the previously characterized
      Cse3 protein allows us to model the interaction of Cas5d with its RNA substrate
      and conclude that it is a member of a larger family of CRISPR RNA endonucleases.

PMID- 23006627
TI  - Low infliximab serum trough levels and anti-infliximab antibodies are prevalent
      in rheumatoid arthritis patients treated with infliximab in daily clinical
      practice: results of an observational cohort study.
AB  - BACKGROUND: To get insight in the prevalence of high, or low/no serum infliximab
      trough levels in patients with low disease activity and if serum trough levels
      are stable and reliable longitudinally we conducted a prospective cohort study
      METHODS: In a longitudinal, observational cohort of RA patients treated with
      infliximab for at least 6 months, treatment interval, DAS28, infliximab trough
      levels and anti-infliximab antibodies were assessed. Prevalence of low (<1 mg/l)
      and high (>5 mg/l) infliximab serum trough levels and anti-infliximab antibodies
      was recorded. Relationship of a change in anti-infliximab antibodies and
      treatment interval was described. Reliability of consecutive infliximab serum
      trough levels and anti-infliximab antibodies in patients with stable DAS28 and
      treatment was analysed with Spearman correlation and kappa-analysis. RESULTS: 147
      patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3)
      at baseline were followed during 1.5 years. Inter-individual variability in
      infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR
      3.35), with 31% (95%CI: 20-42%) having low (<1 mg/L) and 14% (95%CI 5-22) high
      trough levels (>5 mg/L). Interestingly also in RA patients with DAS28 <= 3.2,
      anti-infliximab antibodies were found in one-third of the patients, with half of
      them having antibodies every visit during a median of more than one year.
      Agreement for consecutive measurements of serum trough levels and anti-infliximab
      antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0
      (SE 0.14) Anti-infliximab antibody appearance was influenced by interval
      increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low
      infliximab levels. CONCLUSIONS: Low (and high) infliximab serum trough levels are
      prevalent, interestingly also in patients with low disease activity. Consecutive
      measurements of serum trough levels and anti-infliximab antibodies are reliable
      in stable patients. These test could be used to lower or stop infliximab in
      selected patients.

PMID- 23006628
TI  - The role of a Brucella abortus lipoprotein in intracellular replication and
      pathogenicity in experimentally infected mice.
AB  - Brucella abortus, the causative agent of brucellosis, can survive and replicate
      within host cells. Understanding bacterial virulence factors and bacteria-host
      cell interactions is critical for controlling brucellosis. However, little is
      known regarding the pathogenic mechanisms of brucellosis. A lipoprotein mutant
      (Gene Bank ID: 3339351) of B. abortus showed a lower rate of intracellular
      replication than did the wild-type strain in HeLa cells and RAW 264.7
      macrophages. The adherent activity of the lipoprotein mutant was slightly
      increased compared to that of the wild-type strain in HeLa cells. After infection
      into macrophages, the lipoprotein mutant co-localized with either late endosomes
      or lysosomes. In mice infected with the lipoprotein mutant, fewer lipoprotein
      mutants were recovered from the spleen at 8 weeks post-infection compared to the
      wild-type strain. The ability to protect the lipoprotein mutant against infection
      by the virulent B. abortus strain 544 was similar to that of strain RB51. Our
      results indicate that the B. abortus lipoprotein is an important factor for
      survival within phagocytes and mice, and the B. abortus lipoprotein mutant may
      help improve live vaccines used to control brucellosis.

PMID- 23006629
TI  - School food and nutrition policy, monitoring and evaluation in the USA.
AB  - OBJECTIVE: To provide an overview of school food and nutrition monitoring from
      1980 to the Healthy Hunger-Free Kids Act of 2010 and data on school food
      availability in the USA. DESIGN: A review of the history of school food and
      nutrition policy, monitoring and evaluation efforts in the USA over the past
      three decades. SETTING: USA. SUBJECTS: School food service, school districts and
      schools nationwide. RESULTS: The school food environment in the USA is governed
      by a patchwork of federal, state and local laws and policies. The federal
      government has primary authority over the school meal programmes and has recently
      issued updated regulations governing the food and nutrient requirements for meals
      sold or served through the National School Lunch and School Breakfast Programs.
      Competitive foods (i.e. foods and beverages sold/served outside the meal
      programmes) are governed primarily by state and district laws and policies,
      although new federal regulations are expected to set minimum standards in this
      area. The USA has a long history of data monitoring and evaluation funded by
      government and private foundations which has enabled decision makers to monitor
      progress and opportunities to improve the foods and beverages made available to
      students in school. CONCLUSIONS: School food-related monitoring and evaluation
      research has been highly influential in influencing legislation and policy,
      leading to improvements in the foods and beverages available to children at
      school as part of planned meals and individual items sold outside the meal
      programmes. The lessons learned from the US experience provide insights that may
      be valuable for implementation, monitoring and evaluation of school food
      programmes in other countries.

PMID- 23006630
TI  - Neurology and Don Quixote.
AB  - Don Quixote de la Mancha, which is considered one of the most important and
      influential works of Western modern prose, contains many references of interest
      for almost all of the medical specialties. In this regard, numerous references to
      neurology can be found in Cervantes' immortal work. In this study, we aimed to
      read Don Quixote from a neurologist's point of view, describing the neurological
      phenomena scattered throughout the novel, including tremors, sleep disturbances,
      neuropsychiatric symptoms, dementia, epilepsy, paralysis, stroke, syncope,
      traumatic head injury, and headache; we relate these symptoms with depictions of
      those conditions in the medical literature of the time. We also review Cervantes'
      sources of neurological information, including the works by renowned Spanish
      authors such as Juan Huarte de San Juan, Dionisio Daza Chacon and Juan Valverde
      de Amusco, and we hypothesize that Don Quixote's disorder was actually a
      neurological condition. Although Cervantes wrote it four centuries ago, Don
      Quixote contains plenty of references to neurology, and many of the ideas and
      concepts reflected in it are still of interest.

PMID- 23006631
TI  - The effectiveness of single-dose fosfomycin as antimicrobial prophylaxis for
      patients undergoing transrectal ultrasound-guided biopsy of the prostate.
AB  - OBJECTIVES: It was the aim of this study to evaluate the efficacy of single-dose
      fosfomycin prophylaxis as an alternative to fluoroquinolone-based prophylaxis in
      transrectal ultrasound-guided biopsy of the prostate (TRUSBP). METHODS: We
      evaluated the records of 620 patients who had undergone TRUSBP from January 2010
      to July 2011. Patients received a single dose of 3 g oral fosfomycin or a single
      dose of 500 mg oral levofloxacin or 500 mg oral ciprofloxacin twice daily
      administered for 5 days starting 1 day before the prophylaxis procedure. We
      reviewed all febrile and afebrile urinary tract infections (UTIs) within 1 month
      after TRUSBP. RESULTS: Of the 620 patients, 19 (3.0%) developed febrile UTI and
      51 (8.2%) developed afebrile UTI after biopsy. Of the 19 patients with febrile
      UTI, 1/19 (5.2%) received fosfomycin, 4/19 (21%) received levofloxacin and 14/19
      (73.6%) received ciprofloxacin for prophylaxis. Of the 51 patients with afebrile
      UTI, 4/51 (7.8%) received fosfomycin, 8/51 (15.6%) received levofloxacin and
      39/51 (76.4%) received ciprofloxacin for prophylaxis. There were a total of 10
      fluoroquinolone-resistant infections, and all of them occurred after the
      ciprofloxacin or levofloxacin prophylaxis and none after fosfomycin prophylaxis.
      CONCLUSIONS: The ease of use of fosfomycin, reducing the rate of fluoroquinolone
      resistant infections and hospitalizations shows that it would be an alternative
      and effective drug for antimicrobial prophylaxis in TRUSBP.

PMID- 23006632
TI  - Effect of cholecystokinin on rectal motor and sensory function in patients with
      irritable bowel syndrome and healthy controls.
AB  - AIM: Ingestion of a meal frequently induces an urge to defaecate, the so-called
      gastro-colonic or gastro-rectal reflex. In patients with irritable bowel syndrome
      (IBS), symptoms are often provoked by meals. Cholecystokinin (CCK), a proximal
      gut peptide released after ingestion of a meal, may mediate these postprandial
      changes. The potential role of CCK in rectal sensory and motor function was
      evaluated by a rectal barostat study in healthy controls and patients with IBS.
      METHOD ; The sensory effects on serosal and mucosal receptors were studied.
      Twelve healthy controls and 12 patients with IBS underwent a ramp distension
      procedure of the rectum during infusion of CCK and placebo in random order. In 10
      other healthy controls and 10 IBS patients an intermittent distension procedure
      was performed during infusion of CCK and placebo in random order. RESULTS: No
      differences were found in rectal compliance during ramp distensions between IBS
      patients and controls. CCK did not affect perception of urge and pain in controls
      or in IBS patients. Similar results were obtained during the intermittent
      distensions, but at higher distension pressures CCK significantly increased
      rectal sensitivity in IBS patients. CONCLUSION: Infusion of exogenous CCK to
      plasma levels normally seen in the postprandial state did not influence rectal
      motor function or sensations during ramp distension but it did significantly
      increase pain sensation in IBS patients during rapid intermittent distension.

PMID- 23006633
TI  - Trivaric acid, a potent depside human leukocyte elastase inhibitor.
AB  - Human leukocyte elastase (HLE) is a serine protease implicated in several
      inflammatory diseases, and represents a major target for anti-inflammatory drug
      development. In the present study, nordivaricatic acid (1), divarinyl divarate
      (2), and trivaric acid (3), three depsides isolated from the culture of a soil
      derived fungal strain were identified as inhibitors of HLE. Two didepsides 1 and
      2 showed low inhibitory activity. In contrast, trivaric acid, a para-tridepside,
      exhibited highly potent inhibitory activity with an IC(50) value of 1.8 uM and a
      K(i) of 0.6 uM. Kinetic investigations with trivaric acid showed that this
      inhibition is reversible, competitive pattern. Further studies on the selectivity
      of three depsides toward serine proteases showed that they did not inhibit
      chymotrypsin, trypsin and thrombin even at 150 uM.

PMID- 23006635
TI  - Intraepidermal nerve fiber density and nerve conduction study parameters
      correlate with clinical staging of diabetic polyneuropathy.
AB  - AIM AND METHODS: To assess the usefulness of the diagnostic and staging criteria
      for diabetic polyneuropathy (DP) by the Diabetic Neuropathy Study Group in Japan
      (DNSGJ) we examined clinical features, intraepidermal nerve fiber densities
      (IENFD) and nerve conduction studies (NCS) and coefficient of variation of the R
      R intervals (CVR-R) in 44 patients with diabetes. RESULTS: The patients were
      classified into stage I (n=20), II (n=6), III+IV (n=12), and V (n=6) according to
      the staging criteria by DNSGJ. IENFD decreased as stages progressed (13.8+/-7.1
      fiber/mm in stage I to 0.8+/-1.3 fiber/mm in stage V). Compound motor and sensory
      action potential and motor and sensory nerve conduction velocity decreased with
      progressing stage. F-wave latency prolonged as stages progressed. CVR-R decreased
      with progressing stage (4.41%+/-2.65% in stage I to 1.33%+/-0.57% in stage V).
      IENFD correlated with the various parameters of NCS (r=0.378-0.636, p<0.05) and
      CVR-R (r=0.399, p=0.007). CONCLUSIONS: Clinical staging for DP by DNSGJ reflects
      the results of small and large fiber neuropathy.

PMID- 23006636
TI  - A role for low-abundance miRNAs in colon cancer: the miR-206/Kruppel-like factor
      4 (KLF4) axis.
AB  - BACKGROUND: MicroRNAs (miRNAs or miRs) are short non-coding RNAs that affect the
      expression of genes involved in normal physiology, but that also become
      dysregulated in cancer development. In the latter context, studies to date have
      focused on high-abundance miRNAs and their targets. We hypothesized that among
      the pool of low-abundance miRNAs are some with the potential to impact crucial
      oncogenic signaling networks in colon cancer. RESULTS: Unbiased screening of over
      650 miRNAs identified miR-206, a low-abundance miRNA, as the most significantly
      altered miRNA in carcinogen-induced rat colon tumors. Computational modeling
      highlighted the stem-cell marker Kruppel-like factor 4 (KLF4) as a potential
      target of miR-206. In a panel of primary human colon cancers, target validation
      at the mRNA and protein level confirmed a significant inverse relationship
      between miR-206 and KLF4, which was further supported by miR-206 knockdown and
      ectopic upregulation in human colon cancer cells. Forced expression of miR-206
      resulted in significantly increased cell proliferation kinetics, as revealed by
      real-time monitoring using HCT116 cells. CONCLUSIONS: Evolutionarily conserved
      high-abundance miRNAs are becoming established as key players in the etiology of
      human cancers. However, low-abundance miRNAs, such as miR-206, are often among
      the most significantly upregulated miRNAs relative to their expression in normal
      non-transformed tissues. Low-abundance miRNAs are worthy of further
      investigation, because their targets include KLF4 and other pluripotency and
      cancer stem-cell factors.

PMID- 23006637
TI  - Influence of ischemia before vein grafting on early hyperplasia of the graft and
      the dynamic changes of the intima after grafting.
AB  - BACKGROUND: To investigate both the influence of ischemia before grafting on
      early hyperplasia of the vein grafts, and the dynamic changes of the intima after
      grafting in a rabbit model of vein graft disease. METHODS: We performed paired
      vein graft experiments under different ischemic conditions (15 vs. 60 min; 15 vs.
      90 min) in the neck of the rabbits and compared the differences between the
      grafts. Clopidogrel, an anti-platelet agent, was administered before and after
      surgery. Twenty-eight days after the grafting procedure, the veins were evaluated
      microscopically. The dynamic changes of the intima after grafting were evaluated
      by scanning electron microscopy over time. RESULTS: The vein grafts subjected to
      60- or 90-min ischemia exhibited no differences compared to those subjected to 15
      min ischemia in terms of the mean thickness of the intimal, medial, and
      adventitial layers of the graft. Similarly, there was no difference in the Ki-67
      labeling index (proliferation marker) between the vein grafts. Vein grafts with
      15-min ischemia lost endothelial cells (ECs) but healed by 3 days post graft,
      whereas vein grafts with 90-min ischemia suffered serious EC loss, which was
      restored with new ECs during days 2 to 14 post graft. CONCLUSIONS: Ninety-minute
      ischemia before vein grafting can cause serious EC loss, but does not increase
      early intimal hyperplasia when clopidogrel is administered. Protecting the vein
      from ischemia and reperfusion injury preserves ECs.

PMID- 23006638
TI  - Analysis of longitudinal changes in dyspnea of patients with chronic obstructive
      pulmonary disease: an observational study.
AB  - BACKGROUND: Guidelines recommend that symptoms as well as lung function should be
      monitored for the management of patients with chronic obstructive pulmonary
      disease (COPD). However, limited data are available regarding the longitudinal
      change in dyspnea, and it remains unknown which of relevant measurements might be
      used for following dyspnea. METHODS: We previously consecutively recruited 137
      male outpatients with moderate to very severe COPD, and followed them every 6
      months for 5 years. We then reviewed and reanalyzed the data focusing on the
      relationships between the change in dyspnea and the changes in other clinical
      measurements of lung function, exercise tolerance tests and psychological status.
      Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram
      (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two
      dimensions of disease-specific health status questionnaires of the Chronic
      Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory
      Questionnaire (SGRQ) were also used. Dyspnea at the end of exercise tolerance
      tests was measured using the Borg scale. RESULTS: The mMRC, CRQ dyspnea and SGRQ
      activity significantly worsened over time (p < 0.001), but the OCD did not (p =
      0.097). Multiple regression analyses revealed that the changes in the OCD, mMRC,
      CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced
      expiratory volume in one second (FEV1) (correlation of determination (r2) = 0.05
      0.19), diffusing capacity for carbon monoxide (r2 = 0.04-0.08) and psychological
      status evaluated by Hospital Anxiety and Depression Scale (r2 = 0.14-0.17),
      although these correlations were weak. Peak Borg score decreased rather
      significantly, but was unrelated to changes in clinical measurements. CONCLUSION:
      Dyspnea worsened over time in patients with COPD. However, as different dyspnea
      measurements showed different evaluative characteristics, it is important to
      follow dyspnea using appropriate measurements. Progressive dyspnea was related
      not only to progressive airflow limitation, but also to various factors such as
      worsening of diffusing capacity or psychological status. Changes in peak dyspnea
      at the end of exercise may evaluate different aspects from other dyspnea
      measurements.

PMID- 23006639
TI  - Optimization of anti-Trypanosoma cruzi oxadiazoles leads to identification of
      compounds with efficacy in infected mice.
AB  - We recently showed that oxadiazoles have anti-Trypanosoma cruzi activity at
      micromolar concentrations. These compounds are easy to synthesize and show a
      number of clear and interpretable structure-activity relationships (SAR),
      features that make them attractive to pursue potency enhancement. We present here
      the structural design, synthesis, and anti-T. cruzi evaluation of new oxadiazoles
      denoted 5a-h and 6a-h. The design of these compounds was based on a previous
      model of computational docking of oxadiazoles on the T. cruzi protease cruzain.
      We tested the ability of these compounds to inhibit catalytic activity of
      cruzain, but we found no correlation between the enzyme inhibition and the
      antiparasitic activity of the compounds. However, we found reliable SAR data when
      we tested these compounds against the whole parasite. While none of these
      oxadiazoles showed toxicity for mammalian cells, oxadiazoles 6c (fluorine), 6d
      (chlorine), and 6e (bromine) reduced epimastigote proliferation and were cidal
      for trypomastigotes of T. cruzi Y strain. Oxadiazoles 6c and 6d have IC(50) of
      9.5 +/- 2.8 and 3.5 +/- 1.8 MUM for trypomastigotes, while Benznidazole, which is
      the currently used drug for Chagas disease treatment, showed an IC(50) of 11.3 +/
      2.8 MUM. Compounds 6c and 6d impair trypomastigote development and invasion in
      macrophages, and also induce ultrastructural alterations in trypomastigotes.
      Finally, compound 6d given orally at 50mg/kg substantially reduces the
      parasitemia in T. cruzi-infected BALB/c mice. Our drug design resulted in potency
      enhancement of oxadiazoles as anti-Chagas disease agents, and culminated with the
      identification of oxadiazole 6d, a trypanosomicidal compound in an animal model
      of infection.

PMID- 23006640
TI  - Tobacco smoking among doctors in mainland China: a study from Shandong province
      and review of the literature.
AB  - BACKGROUND: Tobacco control represents a key area in which doctors can make a
      significant positive impact on their patients' lives. Despite this fact, however,
      doctors in certain regions of China are known to smoke tobacco at rates similar
      to or even exceeding those seen within the general population. OBJECTIVE: This
      study sought to investigate the smoking habits of doctors at a teaching hospital
      in Shandong province, as well as providing a brief review of smoking research
      that has been conducted among doctors elsewhere in China. METHOD: An anonymous
      questionnaire survey was distributed to doctors working at a university teaching
      hospital in 2008, as part of a larger study of occupational health issues in the
      healthcare profession. RESULTS: The overall smoking prevalence rate of doctors in
      this study was 36.3% with significant differences observed between the genders
      (males: 46.7% and females: 5.3%). Age and total career length were also
      correlated with smoking habit, although no significant associations were found
      with department of employment. CONCLUSIONS: Overall, our study suggests that
      smoking rates among doctors in Shandong province are higher than those documented
      in many other countries, a finding which is consistent with previous research
      conducted in some other Chinese provinces. Addressing this issue from an
      intrinsic cultural perspective will clearly need to form the cornerstone of
      tobacco control efforts within the Chinese medical community in future years.

PMID- 23006641
TI  - Low cholesterol, statins and outcomes in patients with first-ever acute ischemic
      stroke.
AB  - BACKGROUND: High cholesterol has been associated with better stroke outcomes.
      Conversely, a protective effect of prestroke statin use in the acute phase of
      stroke has been reported. The effect of low cholesterol on outcome in patients
      with and without prestroke statin treatment has not been studied. We assessed the
      association between low cholesterol and ischemic stroke short- and long-term
      outcomes and studied potential interactions with statin treatment in patients
      with a first-ever ischemic stroke in a prospective national registry. METHODS:
      Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry
      with a first-ever stroke and no previous disability, dementia or cancer admitted
      in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were
      included (n = 1,895). Cholesterol levels <=155 mg/dl (1st quintile) were defined
      as low cholesterol and patients treated with statins for at least 7 days before
      stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS
      >=11), total anterior circulation infarction, poor functional outcome (defined as
      discharged to a nursing facility or modified Rankin Scale >3 or death), and
      mortality at discharge and at 3 years were the study outcomes. Associations
      between low cholesterol and outcomes at discharge were assessed separately in
      patients with and without prestroke statin treatment using multiple logistic
      regression analyses. Mortality at 3 years was assessed in a subset of 681
      patients with Cox proportional hazard models. RESULTS: Patients were 67.4 +/-
      13.5 years old on average; 43.1% were women. Low cholesterol was associated with
      higher rates of stroke risk factors. Controlling for age, sex, hypertension,
      diabetes, current smoking, ischemic heart disease, congestive heart failure and
      atrial fibrillation, low cholesterol was significantly associated with severe
      stroke, total anterior circulation infarction and poor functional outcome in
      patients with and without statin treatment. There were no interactions between
      low cholesterol and prestroke statin therapy in association with outcomes. Short-
      and long-term mortality rates were increased for patients with low cholesterol
      (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at
      discharge and 20.5% at 3 years). Adjusted mortality risks were increased for
      patients with low cholesterol; however, this finding was statistically
      significant only for patients not on statins before the stroke. CONCLUSIONS: Low
      cholesterol is associated with increased stroke severity and poorer functional
      outcome in patients with and without prestroke statin use. Low-cholesterol statin
      naive patients show increased risks of mortality. 'Reverse epidemiology' in the
      association between cholesterol and outcome is possible in patients with ischemic
      stroke.

PMID- 23006642
TI  - Derivation of factors for estimating the scatter of diagnostic x-rays from walls
      and ceiling slabs.
AB  - Computed tomography (CT) scanning rooms and interventional x-ray facilities with
      heavy workloads may require the installation of shielding to protect against
      radiation scattered from walls or ceiling slabs. This is particularly important
      for the protection of those operating x-ray equipment from within control
      cubicles who may be exposed to radiation scattered from the ceiling over the top
      of the protective barrier and round the side if a cubicle door is not included.
      Data available on the magnitude of this tertiary scatter from concrete slabs are
      limited. Moreover, there is no way in which tertiary scatter levels can be
      estimated easily for specific facilities. There is a need for a suitable method
      for quantification of tertiary scatter because of the increases in workloads of
      complex x-ray facilities. In this study diagnostic x-ray air kerma levels
      scattered from concrete and brick walls have been measured to verify scatter
      factors. The results have been used in a simulation of tertiary scatter for x-ray
      facilities involving summation of scatter contributions from elements across
      concrete ceiling slabs. The majority of the ceiling scatter air kerma to which
      staff behind a barrier will be exposed arises from the area between the patient/x
      ray tube and the staff. The level depends primarily on the heights of the ceiling
      and protective barrier. A method has been developed to allow tertiary scatter
      levels to be calculated using a simple equation based on a standard arrangement
      for rooms with different ceiling and barrier heights. Coefficients have been
      derived for a CT facility and an interventional suite to predict tertiary scatter
      levels from the workload, so that consideration can be given to the protection
      options available.

PMID- 23006643
TI  - The effects of wearing lower body compression garments during a cycling
      performance test.
AB  - PURPOSE: Compression garments have been commonly used in a medical setting as a
      method to promote blood flow. Increases in blood flow during exercise may aid in
      the delivery of oxygen to the exercising muscles and, subsequently, enhance
      performance. The aim of the current study was to investigate the effect of
      wearing lower body compression garments during a cycling test. METHODS: Twelve
      highly trained cyclists (mean +/- SD age 30 +/- 6 y, mass 75.6 +/- 5.8 kg,
      VO2peak 66.6 +/- 3.4 mL . kg-1 . min-1) performed two 30-min cycling bouts on a
      cycle ergometer in a randomized, crossover design. During exercise, either full
      length lower body compression garments (COMP) or above-knee cycling shorts (CON)
      were worn. Cycling bouts involved 15 min at a fixed workload (70% of VO2max
      power) followed by a 15-min time trial. Heart rate (HR) and blood lactate (BL)
      were measured during the fixed-intensity component of the cycling bout to
      determine the physiological effect of the garments. Calf girth (CG), thigh girth
      (TG) and perceived soreness (PS) were measured preexercise and postexercise.
      RESULTS: COMP produced a trivial effect on mean power output (ES = .14) compared
      with CON (mean +/- 95% CI 1.3 +/-1.0). COMP was also associated with a lower HR
      during the fixed-workload section of the test (-2.6% +/- 2.3%, ES = -.38). There
      were no differences between groups for BL, CG, TG, and PS. CONCLUSION: Wearing
      compression garments during cycling may result in trivial performance
      improvements of ~1% and may enhance oxygen delivery to the exercising muscles.

PMID- 23006644
TI  - What is wrong with this picture?

PMID- 23006645
TI  - The importance of nursing faculty mentoring.

PMID- 23006646
TI  - Spirituality-based nursing practice by nursing students: an exploration study.

PMID- 23006647
TI  - The differing learning styles and preferences of baccalaureate and accelerated
      nursing students pursuing higher degrees.

PMID- 23006648
TI  - Doctor of nursing practice programs across the United States: a benchmark of
      information: part I: program characteristics.
AB  - The number of doctor of nursing practice (DNP) programs in the United States has
      dramatically increased. To date, there is a lack of benchmark data regarding DNP
      program attributes; thus, the purpose of this investigation was to generate such
      a database. Because of the volume of information gathered, the results are
      presented in a two-part article. Part I consists of DNP program characteristics,
      which include location of program, type of program, delivery, plan of study,
      program length, number of credits, cost, program tracks, practice course name,
      review of programs still offering the master's degree for advanced practice
      nurses (APNs), and the availability of nursing education electives. Part II
      consists of information regarding DNP admission criteria. A cross-sectional,
      descriptive design was used to explore 137 DNP programs across the United States.
      Data were collected exclusively via university Web sites. Descriptive statistics
      including frequencies, percentages, means, and standard deviations were
      calculated and presented in report, table, or figure format. This comprehensive
      DNP program characteristic database is the first, to our knowledge, that is
      available for review. As universities prepare to develop, amend, and seek
      accreditation for their DNP programs, knowledge of these characteristics would be
      helpful to compare, contrast, and construct curricula.

PMID- 23006649
TI  - Doctor of nursing practice programs across the United States: a benchmark of
      information: part II: admission criteria.
AB  - The adoption of the doctor of nursing practice (DNP) degree by the American
      Association of Colleges of Nursing has led to the exponential growth of DNP
      programs across the United States. This article is Part II of a 2-part series
      exploring DNP program information. The purpose of this research was to create a
      benchmark of information that can be used to compare and contrast programs
      throughout the United States. Part I discussed DNP program characteristics. Part
      II consists of DNP admission criteria that include graduate record examination
      (GRE) requirements, grade point average (GPA), national certification, degree
      requirements, specialty foci, clinical hours, and prerequisite courses. A cross
      sectional, descriptive design was used to explore 137 DNP programs across the
      United States. Data were collected exclusively via university Web sites.
      Descriptive statistics were calculated and presented in report, table, or figure
      format. As we move forward with the DNP, effective selection of students is of
      critical importance because admission and retention of outstanding candidates
      will ultimately strengthen the field of nursing. The data generated by this
      research provides programs with a starting point for discussion regarding
      admission criteria for the DNP degree.

PMID- 23006650
TI  - The impact of a virtual community on student engagement and academic performance
      among baccalaureate nursing students.
AB  - The purpose of this article is to present findings from a study which evaluated
      the effectiveness of a virtual community (an emerging pedagogical application) on
      student engagement and academic performance. Virtual communities mirror real-life
      through unfolding patient histories and relationship development over time.
      Students also become more engaged in learning by creating personally meaningful
      knowledge of a concept (Rogers & Stone, 2007). Virtual communities offer one
      teaching strategy to assist students in learning complex, health-related content
      in a contextualized manner. This quasi-experimental study involved first-semester
      baccalaureate nursing students enrolled in a course at two campuses of a nursing
      program at a large university in the Southwest. Three key strategies assessed the
      impact of the virtual community on student engagement and learning: third-party
      observational measurement, end-of-class student/faculty surveys, and use of
      knowledge items in student exams for the class. Significant differences between
      the control and experimental group were found regarding learning engagement and
      communication exchanges; the groups appeared similar in ratings of quality of
      instruction and academic performance. Use of virtual communities can help nursing
      educators address the recent Carnegie Foundation study's (Benner, Sutphen,
      Leonard & Day, 2010) counsel to implement "pedagogies of contextualization" in
      which theoretical and factual information about diseases and conditions are
      placed in the context of a patient's experience.

PMID- 23006651
TI  - Evaluating undergraduate nursing students' learning using standardized patients.
AB  - BACKGROUND: The use of standardized patients is an established training technique
      in medical education. However, this problem-based learning approach is relatively
      new to the field of nursing education. Its benefits to undergraduate nursing
      education continue to be underinvestigated in the nursing literature. PURPOSE:
      The purpose of this study was to examine the effectiveness of using standardized
      patients in improving health assessment skills among first-year nursing students.
      METHODS: A comparative design was conducted on a convenience sample of 108 first
      year undergraduate nursing students. Study participants were recruited from a
      university and community college collaborative nursing program in southwestern
      Ontario. RESULTS: Analysis of covariance results showed that after adjusting for
      baseline differences, the intervention group had higher objective structured
      clinical examination mean scores than the control group (M = 78.57 and 69.28, F =
      24.13, P <= .001). However, the two groups were not different in their theory
      scores (M = 77.23 and 77.29, F = .002, P = .963). CONCLUSION: The findings
      suggest that the use of standardized patients is an effective educational
      technique in undergraduate nursing education.

PMID- 23006652
TI  - Foreign-born nursing students in the United States: a literature review.
AB  - A thorough search of the literature examined what have been reported as stressors
      for foreign-born nursing students living in the United States. A comprehensive
      review of foreign-born nursing student literature within the United States
      educational system was examined, reviewed, and summarized. Minimal research has
      been dedicated exclusively to identify those unique stressors experienced among
      the foreign-born student population. A review of 11 articles revealed four common
      results interdependent of one another experienced among this group of students.
      Results identified were (a) language and communication issues; (b)
      discrimination, prejudice, and lack of support; (c) cultural issues; and (d)
      loneliness, isolation, and alienation. Foreign-born nursing students may continue
      to experience a multitude of barriers while seeking educational advancements in
      the United States until serious endeavors are initiated to close the gap and
      address the concerns previously documented. Although the needs of this diverse
      population are important, this research has the potential to reveal crucial
      information regarding stressors specifically common to those studying abroad in
      the United States. This topic will provide guidance to deans, directors, and
      educators in identifying and establishing processes to help validate the foreign
      born nursing students' experience while they are enrolled in their prospective
      schools of nursing within the United States.

PMID- 23006653
TI  - Horizontal violence among hospital staff nurses related to oppressed self or
      oppressed group.
AB  - Horizontal violence among nurses is recognized as a major problem in hospitals;
      however, the origins and effects on patient care have not been studied. This
      study described the incidence of horizontal violence among hospital staff RNs and
      tested 2 hypotheses about the social origins of this behavior. A random sample of
      175 hospital staff RNs drawn from the California Board of Registered Nursing's
      mailing list was surveyed. Horizontal violence was reported by 21.1% (n = 37) of
      participating nurses. Hypotheses were supported. Findings suggested (a) a
      positive relationship between beliefs consistent with an oppressed self and
      horizontal violence (r = .434, P < .05) and (b) a positive relationship between
      beliefs consistent with those of an oppressed group and horizontal violence (r =
      .453, P < .05). A change in the oppressive social structure of hospitals may be
      needed to truly address horizontal violence in the best interest of the quality
      and safety of patient care.

PMID- 23006654
TI  - Measuring effectiveness of a spiritual care pedagogy in nursing education.
AB  - Nurses have long recognized the importance of spiritual care in nursing practice
      as promoting the integration of meaning and purpose in life. More recently, both
      the American Nurses Association incorporates spiritual care in the Scope and
      Standards of Nursing Practice and the American Association of Colleges of Nursing
      has integrated spiritual care in the Essentials of Baccalaureate Education.
      However, research suggests that nurses do not know how to provide spiritual care.
      This study developed and tested a spiritual care pedagogy. In phase I,
      researchers designed a spiritual care educational and reflective program based on
      the Burkhart/Hogan theory of spiritual care in nursing practice, incorporating
      face-to-face and on-line components. In phase 2, the effectiveness of this
      program was measured in a pre-post test, randomized controlled trial with senior
      nursing students during their capstone clinical immersion course (n=59). Findings
      revealed a statistically significant increase in students' perceived ability in
      providing spiritual care, particularly in complex family clinical situations.
      Findings also indicated a significant increase in the student's use of reflective
      practices, which students found to help support them during stressful times. This
      study translates nursing theory and research into a successful pedagogy.

PMID- 23006656
TI  - Advances and pitfalls of cell therapy in metabolic leukodystrophies.
AB  - Leukodystrophies are a group of disorders characterized by myelin dysfunction,
      either at the level of myelin formation or maintenance, that affect the central
      nervous system (CNS) and also in some cases, to a lesser extent, the peripheral
      nervous system (PNS). Although these genetic-based  disorders are generally rare,
      all together they have a significant impact in the society, with an estimated
      overall incidence of 1 in 7,663 live births. Currently, there is no cure for
      leukodystrophies, and the development of effective treatments remains
      challenging. Not only leukodystrophies  generally progress very fast, but also
      most are multifocal needing the simultaneous targeting at multiple sites.
      Moreover, as the CNS is affected, the blood-brain barrier (BBB) limits the
      efficacy of treatment. Recently, interest on cell therapy has increased, and the
      leukodystrophies  for which metabolic correction is needed have become first
      choice candidates for cell-based clinical trials. In this review, we present and
      discuss the available cell transplantation therapies in metabolic
      leukodystrophies including fucosidosis, X-linked adrenoleukodystrophy,
      metachromatic  leukodystrophy, Canavan disease, and Krabbe's disease. We will
      discuss the latest advances of cell therapy and its pitfalls in this group of
      disorders, taking into account, among others, the limitations imposed by reduced
      cell migration in multifocal conditions, the need to achieve corrective  enzyme
      threshold levels, and the growing awareness that not only myelin but also the
      associated axonopathy needs to be targeted in some leukodystrophies.

PMID- 23006655
TI  - The age- and sex-specific occurrence of bothersome neck pain in the general
      population--results from the Stockholm public health cohort.
AB  - BACKGROUND: Neck pain is very common but the occurrence of bothersome neck pain
      is not well described. Therefore our objective was to report on the prevalence
      and incidence of, as well as the rate of recovery from, bothersome neck pain in
      men and women of different ages in the general population. METHODS: We used data
      from a recently conducted population-based cohort study, comprising 23,794
      individuals in Stockholm County, Sweden. Study participants were surveyed with a
      self-administered questionnaire in 2002/2003 and 2007, and information on
      episodes of neck pain was gathered at baseline and at follow-up. We then measured
      bothersome neck pain in 2005 and 2006 retrospectively in 2007 using the follow-up
      questionnaire. RESULTS: The one-year prevalence of bothersome neck pain for at
      least seven consecutive days was 25% (95% confidence interval (CI): 24-25) among
      women and 16% (95% CI: 15-16) among men, peaking in individuals aged 30-59 years.
      The one-year incidence proportion of bothersome neck pain was 7% (95% CI: 6-7)
      among women, and 4% (95% CI: 4-5) among men. Women recovered more infrequently
      than men. The one-year incidence proportion of recovery (of at least one year
      duration) was 11% (95% CI: 10-12) among women and 14% (95% CI: 12-16) among men.
      CONCLUSION: Bothersome neck pain is most common in middle-aged individuals. Women
      are more likely than men to have and to develop bothersome neck pain, and less
      likely to recover from such pain. Younger men and women have a higher incidence,
      but recover more often from bothersome neck pain than older individuals.

PMID- 23006658
TI  - Acute simultaneous multiple lacunar infarcts: a severe disease entity in small
      artery disease.

PMID- 23006657
TI  - Randomised trial investigating the relationship of response rate for blood sample
      donation to site of biospecimen collection, fasting status and reminder letter:
      the 45 and Up Study.
AB  - BACKGROUND: Various options exist for collecting biospecimens and biomarkers from
      cohort study participants, and these have important logistic, resource and
      scientific implications. Evidence on how different collection methods affect
      participation and data quality is lacking. This parallel-design randomised trial,
      the Link-Up Study, involved blood sample donation and other data collection among
      participants in an existing cohort study, The 45 and Up Study. It aimed to
      investigate the relation of fasting status, reminder letters and data collection
      site to response rates, data quality and biospecimen yield. METHODS: Individuals
      aged 45 and over participating in The 45 and Up Study and living <= 20 km from
      central Wagga Wagga, NSW (regional area) or <= 10 km from central Parramatta, NSW
      (urban area) (n=2340) were randomised, stratified by area of residence, to be
      invited to give a blood sample and additional data by attending either a clinic
      established specifically for the trial, with an appointment time ("dedicated
      clinic", n=1336) or an existing local commercial pathology centre (n=1004).
      Within dedicated clinic groups, participants were randomised into fasting (n=668)
      or non-fasting (n=668) and, at the Parramatta pathology centre site, reminder
      letter after two weeks (n=336) or no reminder (n=334). RESULTS: Overall, 33%
      (762/2340) of invitees took part in the Link-Up Study; 41% (410/1002) among
      regional and 26% (352/1338) among urban-area residents (p<0.0001). At the
      dedicated clinics, response rates were 38% (257/668) not fasting and 38% fasting
      (257/668) (participation rate ratio (RR) =1.00, 95%CI 0.91-1.08, p=0.98). The
      response rate was 22% among individuals randomised to attend the Parramatta
      pathology centre without a reminder and 23% among those sent a reminder letter
      (RR=1.01, 0.93-1.09, p=0.74). In total, the response rate was 38% (514/1336) at
      the dedicated clinics and 25% (248/1004) at the pathology centres (RR=0.67, 0.56
      0.78, p<0.01); measures of height, weight and systolic and diastolic blood
      pressure did not vary materially between these groups, nor did the median number
      of aliquots of plasma, buffy coat and red cells collected. CONCLUSIONS: Among
      cohort study participants, response rates for an additional study involving
      biospecimen collection, but not data quality or average biospecimen yield, were
      considerably higher at dedicated clinics than at existing commercial pathology
      sites.

PMID- 23006659
TI  - Astragalus polysaccharides enhance immune responses of HBV DNA vaccination via
      promoting the dendritic cell maturation and suppressing Treg frequency in mice.
AB  - Astragalus polysaccharides (APS), an extract from a kind of Chinese traditional
      herb Astragalus membranaceus, was proved to have strong immunoregulatory
      properties. In this study, APS was employed as an adjuvant of Hepatitis B virus
      (HBV) DNA vaccine (pcDS2) and its' effects on immune system of mice were
      investigated. Our data demonstrated that APS as an adjuvant could increase the
      HBsAg-specific antibody level as well as the proliferating activity of T cells.
      APS also could induce CD4(+) T cells to produce IL-4, IL-2 and IFN-gamma and
      enhance IFN-gamma expression of CD8(+) T cells. Moreover, APS could induce the
      robust activity of the cytotoxic lymphocytes (CTL). Additionally, APS could
      stimulate the dendritic cells (DC) maturation which is characterized by up
      regulation of MHC I/II, CD40, CD80 and CD86, and decreased the frequency of the
      regulatory T cells (nTreg). Collectively, these findings suggest that APS is a
      potent adjuvant for the hepatitis B DNA vaccine and can enhance the immune
      responses of HBV DNA vaccine via promoting DC maturation and inhibit the Treg
      frequency.

PMID- 23006660
TI  - Sucralfate or placebo following argon plasma coagulation for chronic radiation
      proctitis: a randomized double blind trial.
AB  - AIM: Chronic radiation proctitis is a long-term complication of radiation therapy
      for pelvic malignancy. The aim of this study was to compare the efficacy and
      safety of two treatment regimens, sucralfate or placebo, following argon plasma
      coagulation (APC) for chronic haemorrhagic radiation proctitis. METHOD: A single
      centre, randomized, placebo-controlled, double-blind study was performed on
      patients with haemorrhagic chronic radiation proctitis after irradiation for
      prostate, uterine, cervical, rectal or vaginal cancer. All patients received APC,
      and were then randomized to oral sucralfate (6 g twice a day) or placebo
      treatment for 4 weeks. APC was repeated every 8 weeks if necessary after the
      first session. Patients were graded clinically and endoscopically according to
      the Chutkan and Gilinski scales before and at 8 and 16 weeks after initial APC
      treatment (1.5-2 l/min, 25-40 W) and after 52 weeks (clinical only). RESULTS: Of
      122 patients, 117 completed the entire protocol, with 57/60 in the sucralfate
      group and 60/62 in the placebo group. At baseline there were no significant
      differences between the sucralfate and placebo groups. At 1 year, a significant
      improvement in the clinical scale in both groups occurred compared with baseline.
      After 16 weeks, the median overall clinical severity scores fell from 4 to 2
      points and the median bleeding score from 2 to 0 in both groups. CONCLUSION: APC
      is safe and effective for the management of chronic radiation proctitis.
      Additional sucralfate treatment did not influence the clinical or endoscopic
      outcome.

PMID- 23006662
TI  - Multivariate analysis of prognostic factors in patients with rapidly progressive
      alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is a common acquired hair disorder showing
      variable hair loss. Although various prognostic factors have been reported, no
      evident factors for determining prognosis and appropriate treatment are known.
      OBJECTIVE: To identify prognostic factors in AA patients, especially those with
      positive results for the hair-pull test on the first visit or with a history of
      rapidly progressive AA (RPAA) within 6 months prior to the first visit. METHODS:
      One thousand thirty (1030) patients diagnosed with AA at Tokyo Medical University
      Hospital were retrospectively examined for 3 years, and their prognosis was
      assessed on the basis of various indices using multivariate analysis. RESULTS:
      Patients with regenerated vellus hairs showed a significantly higher improvement
      or cure rate regardless of severity. Early onset and lengthy duration were
      significantly associated with lower cure, and higher relapse, rates. RPAA
      patients tended to show a good prognosis regardless of the treatment employed.
      LIMITATIONS: The present study is retrospective, and treatment modalities were
      chosen according to clinical and social circumstances. CONCLUSION: RPAA patients
      tend to show a favorable prognosis regardless of treatment modality. Furthermore,
      the presence of regenerated vellus hairs may indicate a good prognosis.

PMID- 23006663
TI  - 5-HT(1A) receptors transactivate the platelet-derived growth factor receptor type
      beta in neuronal cells.
AB  - In the absence of ligand, certain growth factor receptors can be activated via G
      protein coupled receptor (GPCR) activation in a process termed transactivation.
      Serotonin (5-HT) receptors can transactivate platelet-derived growth factor
      (PDGF) beta receptors in smooth muscle cells, but it is not known if similar
      pathways occur in neuronal cells. Here we show that 5-HT can transiently increase
      the phosphorylation of PDGFbeta receptors through 5-HT(1A) receptors in a time-
      and dose-dependent manner in SH-SY5Y neuroblastoma cells. 5-HT also
      transactivates PDGFbeta receptors in primary cortical neurons. This
      transactivation pathway is pertussis-toxin sensitive and Src tyrosine kinase
      dependent. This pathway is also dependent on phospholipase C activity and
      intracellular calcium signaling. Several studies involving PDGFbeta receptor
      transactivation by GPCRs have also demonstrated a PDGFbeta receptor-dependent
      increase in the phosphorylation of ERK1/2. Yet in SH-SY5Y cells, 5-HT treatment
      causes a PDGFbeta receptor-independent increase in ERK1/2 phosphorylation. This
      crosstalk between 5-HT and PDGFbeta receptors identifies a potentially important
      signaling link between the serotonergic system and growth factor signaling in
      neurons.

PMID- 23006664
TI  - PLCbeta isoforms differ in their subcellular location and their CT-domain
      dependent interaction with Galphaq.
AB  - Phospholipase C (PLC) beta isoforms are implicated in various physiological
      processes and pathologies. However, mechanistic insight into the localization and
      activation of each of the isoforms is limited. Therefore, it is crucial to gain
      more in-depth knowledge as to the regulation of the different isoforms. Here we
      describe the subcellular location of full-length PLCbeta isozymes and their C
      terminal (CT) domains. Strikingly, we found isoforms PLCbeta1 and PLCbeta4 to be
      enriched at the plasma membrane, contrary to isoforms PLCbeta2 and PLCbeta3. We
      determined that the CT domain is an inhibitor of Gq-mediated increases in
      intracellular calcium, the potency of its effect being dependent upon the CT
      domain isoform used. Furthermore, ratiometric fluorescence resonance energy
      transfer (FRET) imaging was used to study the kinetics of the Galphaq-CTbetax
      interactions. By the use of recently developed tools, which enable the on-demand
      activation of Galphaq, we could show that the interaction between constitutively
      active Galphaq and PLCbeta3 prolongs the residence time of PLCbeta3 at the plasma
      membrane. These findings suggest that under physiological circumstances, PLCbeta3
      and Galphaq interact in a kiss-and-run fashion, likely due to the GTPase
      activating activity of PLCbeta towards Galphaq.

PMID- 23006665
TI  - The more physically active, the healthier? The relationship between physical
      activity and health-related quality of life in adolescents: the MoMo study.
AB  - BACKGROUND: Little is known about the relationship between physical activity and
      health-related quality of life (HRQOL) in adolescents. The purpose of this study
      was 1) to quantify the predictive power of greater physical activity on higher
      HRQOL in adolescents and 2) to analyze whether the prediction is better for the
      sports club setting than for the leisure time setting. METHODS: Within the
      framework of the German Health Interview and Examination Survey for Children and
      Adolescents and the "Motorik-Modul," 1828 German adolescents aged 11-17 years
      completed a questionnaire concerning the amount of weekly physical activity at
      school, in sports clubs, and during leisure time. The KINDL-R questionnaire was
      used to assess HRQOL. Linear and multiple regression analyses were used to
      analyze the effects of physical activity on HRQOL. RESULTS: In regression
      analyses controlling for sociostructural variables, greater general physical
      activity was a significant predictor of higher HRQOL (P < .001). While greater
      physical activity in sports clubs significantly predicted higher HRQOL, greater
      physical activity during leisure time predicted higher HRQOL only to a certain
      level. Overall, the level of explained variance was low. CONCLUSIONS: Being
      physically active especially in sports clubs is positively linked to higher HRQOL
      of adolescents.

PMID- 23006666
TI  - High-prevalence and broad spectrum of Cell Adhesion and Extracellular Matrix gene
      pathway mutations in epithelial ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is the most deadly gynecological cancer because of
      late diagnosis, frequently with diffuse peritoneal metastases. Recent findings
      have shown that serous epithelial ovarian cancer has a narrow mutational spectrum
      with TP53 being the most frequently targeted when single genes are considered. It
      is, however, important to understand which pathways as a whole may be targeted
      for mutation. FINDINGS: Previously published mutational data provided by the
      cancer genome atlas networks findings on ovarian cancer was searched for
      statistically significant enrichment of genes in pathways. These pathways were
      then searched in all patients to identify the spectrum of mutations. Statistical
      significance was further shown through in-silico permutations of exome sequences
      using empirically observed mutation rates. We detected mutations in the cell
      adhesion pathway genes in more than 89% of serous epithelial ovarian cancer
      patients. This level of near universal mutational targeting of the cell adhesion
      pathway, including the extracellular matrix pathway, is previously unreported in
      epithelial ovarian cancer. CONCLUSIONS: Taken together with previous studies on
      the role of cell adhesion and extracellular matrix gene expression in ovarian
      cancer and metastasis, our results identify pathways for which the mutational
      prevalence has previously been overlooked using single gene approaches. Analysis
      of mutations at the pathway level will be critical in studying heterogeneous
      diseases such as ovarian cancer.

PMID- 23006667
TI  - Radioactive impact in South Korea from the damaged nuclear reactors in Fukushima:
      evidence of long and short range transport.
AB  - Traces of long-lived fallout-derived radioisotopes ((134)Cs and (137)Cs) were
      found in wet and dry deposition samples collected from the west and east coasts
      of South Korea from March to May 2011 following the release of radionuclides from
      the damaged nuclear power plants in Fukushima, Japan. The analysis of air mass
      back trajectory and atmospheric pressure systems indicated that the Fukushima
      derived radiocaesium had predominantly reached South Korea from the west by
      surface westerlies from 11 March to 5 April; however, after 6 April, air masses
      arrived from Japan directly due to a high pressure system that developed to the
      east of Japan. Spatial variation of deposition fluxes of radiocaesium in South
      Korea was partly attributed to the presence of local longitudinal orography.

PMID- 23006668
TI  - Epilepsy care guidelines for low- and middle- income countries: From WHO mental
      health GAP to national programs.
AB  - In 2011, the World Health Organization's (WHO) mental health Gap Action Programme
      (mhGAP) released evidence-based epilepsy-care guidelines for use in low and
      middle income countries (LAMICs). From a geographical, sociocultural, and
      political perspective, LAMICs represent a heterogenous group with significant
      differences in the epidemiology, etiology, and perceptions of epilepsy.
      Successful implementation of the guidelines requires local adaptation for use
      within individual countries. For effective implementation and sustainability, the
      sense of ownership and empowerment must be transferred from the global health
      authorities to the local people. Sociocultural and financial barriers that impede
      the implementation of the guidelines should be identified and ameliorated. Impact
      assessment and program revisions should be planned and a budget allocated to
      them. If effectively implemented, as intended, at the primary-care level, the
      mhGAP guidelines have the potential to facilitate a substantial reduction in the
      epilepsy treatment gap and improve the quality of epilepsy care in resource
      limited settings.

PMID- 23006669
TI  - Arterial spin labeling imaging findings in transient ischemic attack patients:
      comparison with diffusion- and bolus perfusion-weighted imaging.
AB  - BACKGROUND: Since transient ischemic attacks (TIAs) can predict future stroke, it
      is important to distinguish true vascular events from non-vascular etiologies.
      Arterial spin labeling (ASL) is a non-contrast magnetic resonance (MR) method
      that is sensitive to cerebral perfusion and arterial arrival delays. Due to its
      high sensitivity to minor perfusion alterations, we hypothesized that ASL
      abnormalities would be identified frequently in TIA patients, and could therefore
      help increase clinicians' confidence in the diagnosis. METHODS: We acquired
      diffusion-weighted imaging (DWI), intracranial MR angiography (MRA), and ASL in a
      prospective cohort of TIA patients. A subset of these patients also received
      bolus contrast perfusion-weighted imaging (PWI). Two neuroradiologists evaluated
      the images in a blinded fashion to determine the frequency of abnormalities on
      each imaging sequence. Kappa (K) statistics were used to assess agreement, and
      the chi(2) test was used to detect differences in the proportions of abnormal
      studies. RESULTS: 76 patients met the inclusion criteria, 48 (63%) of whom
      received PWI. ASL was abnormal in 62%, a much higher frequency compared with DWI
      (24%) and intracranial MRA (13%). ASL significantly increased the MR imaging
      yield above the combined DWI and MRA yield (62 vs. 32%, p < 0.05). Arterial
      transit artifact in vascular borderzones was the most common ASL abnormality
      (present in 51%); other abnormalities included focal high or low ASL signal
      (11%). PWI was abnormal in 31% of patients, and in these, ASL was abnormal in 14
      out of 15 cases (93%). In hemispheric TIA patients, both PWI and ASL findings
      were more common in the symptomatic hemisphere. Agreement between
      neuroradiologists regarding abnormal studies was good for ASL and PWI [K = 0.69
      (95% CI 0.53-0.86) and K = 0.66 (95% CI 0.43-0.89), respectively]. CONCLUSION: In
      TIA patients, perfusion-related alterations on ASL were more frequently detected
      compared with PWI or intracranial MRA and were most frequently associated with
      the symptomatic hemisphere. Almost all cases with a PWI lesion also had an ASL
      lesion. These results suggest that ASL may aid in the workup and triage of TIA
      patients, particularly those who cannot undergo a contrast study.

PMID- 23006671
TI  - Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain
      model in mice: a pharmacokinetic-pharmacodynamic study.
AB  - Facilitation of spinal GABAergic inhibition with benzodiazepines (BZDs) reverses
      pain sensitization in animals; however, the use of BZDs in man is limited by
      their sedative effect. The antihyperalgesic effects of GABA(A) agonists are
      mediated by GABA(A) receptors containing alpha2 subunits, whereas sedation is
      linked to alpha1 subunit-containing receptors. alpha2 and alpha3 selective
      GABA(A) receptor modulators have been tested in animals but are not yet available
      for use in human beings. Clobazam is a 1,5-BZD, which exhibits less cognitive
      side effects than other benzodiazepines. Here, we studied its antihyperalgesic
      effects in a mouse model of neuropathic pain. Clobazam showed a dose-dependent
      antihyperalgesic effect in the chronic constriction injury (CCI) model of
      neuropathic pain, peaking at 1 hr after administration and lasting for 4 hr with
      no relevant sedation at a dose of 3 mg/kg. At higher doses, the antihyperalgesic
      effect was stronger, but sedation became significant. The blood and brain
      kinetics of clobazam were linear over the range of doses tested with a short half
      life of the parent compound and a ready penetration of the blood-brain barrier.
      Clobazam blood concentrations decreased rapidly, falling below the limit of
      detection at 120 min. after drug application. Its main metabolite, N-desmethyl
      clobazam, showed more delayed and prolonged pharmacokinetics, partly explaining
      why antihyperalgesia persisted when clobazam was no longer detectable in the
      blood. Considering its therapeutic margin and its pharmacokinetic properties,
      clobazam would be a valuable compound to assess the role of the GABAergic pathway
      in pain transmission in human beings.

PMID- 23006670
TI  - Systems biology of circadian-immune interactions.
AB  - There is increasing evidence that the immune system is regulated by circadian
      rhythms. A wide range of immune parameters, such as the number of red blood cells
      and peripheral blood mononuclear cells as well as the level of critical immune
      mediators, such as cytokines, undergo daily fluctuations. Current experimental
      data indicate that circadian information reaches immune tissues mainly through
      diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors
      such as cytokines can also influence the phase of the circadian clock, providing
      bidirectional flow of circadian information between the neuroendocrine and immune
      systems. This network of neuroendocrine-immune interactions consists of complexly
      integrated molecular feedback and feedforward loops that function in synchrony in
      order to optimize immune response. Chronic stress can disrupt this intrinsic
      orchestration, as several endocrine signals of chronically stressed patients
      present blunted rhythmic characteristics. Reprogramming of biological rhythms has
      recently gained much attention as a potent method to leverage homeostatic
      circadian controls to ultimately improve clinical outcomes. Elucidation of the
      intrinsic properties of such complex systems and optimization of intervention
      strategies require not only an accurate identification of the signaling pathways
      that mediate host responses, but also a system-level description and evaluation.

PMID- 23006672
TI  - Effect of anticoagulation regimens on handling of interleukin-6 and -8 during
      continuous venovenous hemofiltration in critically ill patients with acute kidney
      injury.
AB  - OBJECTIVE: During continuous venovenous hemofiltration (CVVH) to replace renal
      function in acute kidney injury (AKI), anticoagulation of the filter is routinely
      required. A survival benefit for citrate has been reported, possibly due to
      reduced proinflammatory effects of the filter (bioincompatibility). We
      hypothesized that the type of anticoagulation modulates the immune response to,
      and clearance by CVVH of interleukin-6 (IL-6) and -8 (IL-8). METHODS: Three
      anticoagulation regimens were compared: trisodium citrate (n=17), unfractionated
      heparin (n=8) and no anticoagulation in case of bleeding tendency (n=13).
      Immediately before initiation of CVVH (cellulose triacetate membrane) pre-filter
      blood was drawn. Thereafter, at 10, 60, 180 and 720 min, samples were collected
      from the pre- and postfilter blood and from ultrafiltrate. IL-6 and IL-8 were
      determined by ELISA. RESULTS: High inlet levels of IL-6 and IL-8, particularly in
      the no anticoagulation group, were associated with non-survival. The inlet
      concentrations and mass rates of IL-6 and IL-8 decreased during CVVH. The course
      of fluxes across the filter were similar for the groups, however. Although
      increasing in time for IL-6 in the no anticoagulation group, mass removal and
      adsorption of IL-6 and IL-8 were low and did not differ among the anticoagulation
      groups. CONCLUSIONS: Blood to membrane contact, adsorption/clearance and
      anticoagulation do not increase nor attenuate high circulating levels of IL-6 and
      IL-8 during CVVH for AKI. This renders the hypothesis that the reported survival
      benefit for citrate anticoagulation is based on a reduction of bioincompatibility
      unlikely.

PMID- 23006673
TI  - Effects of electrostimulation therapy on recovery from acute team-sport activity.
AB  - PURPOSE: To assess the efficacy of a 1-off electrostimulation treatment as a
      recovery modality from acute team-sport exercise, directly comparing the benefits
      to contrast water therapy. METHODS: Ten moderately trained male athletes
      completed a simulated team-game circuit (STGC). At the conclusion of exercise,
      participants then completed a 30-min recovery modality of either
      electrostimulation therapy (EST), contrast water therapy (CWT), or a passive
      resting control condition (CON). Twenty-four hours later, participants were
      required to complete a modified STGC as a measure of next-day performance. Venous
      blood samples were collected preexercise and 3 and 24 h postexercise. Blood
      samples were analyzed for circulating levels of interleukin-6 (IL-6) and C
      reactive protein (CRP). RESULTS: The EST trial resulted in significantly faster
      sprint times during the 24-h postrecovery than with CON (P < .05), with no
      significant differences recorded between EST and CWT or between CWT and CON (P >
      .05). There were no differences in IL-6 or CRP across all trials. Finally, the
      perception of recovery was significantly greater in the EST trial than in the CWT
      and CON (P < .05). CONCLUSIONS: These results suggest that a 1-off treatment with
      EST may be beneficial to perceptual recovery, which may enhance next-day
      performance.

PMID- 23006674
TI  - Upper limb position control in fibromyalgia.
AB  - BACKGROUND: Motor problems are reported by patients with fibromyalgia (FM).
      However, the mechanisms leading to alterations in motor performance are not well
      understood. In this study, upper limb position control during sustained isometric
      contractions was investigated in patients with FM and in healthy controls (HCs).
      METHODS: Fifteen female FM patients and 13 HCs were asked to keep a constant
      upper limb position during sustained elbow flexion and shoulder abduction,
      respectively. Subjects received real-time visual feedback on limb position and
      both tasks were performed unloaded and while supporting loads (1, 2, and 3 kg).
      Accelerations of the dominant upper limb were recorded, with variance (SD of mean
      position) and power spectrum analysis used to characterize limb position control.
      Normalized power of the acceleration signal was extracted for three frequency
      bands: 1-3 Hz, 4-7 Hz, and 8-12 Hz. RESULTS: Variance increased with load in both
      tasks (P < 0.001) but did not differ significantly between patients and HCs (P >
      0.17). Power spectrum analysis showed that the FM patients had a higher
      proportion of normalized power in the 1-3 Hz band, and a lower proportion of
      normalized power in the 8-12 Hz band compared to HCs (P < 0.05). The results were
      consistent for all load conditions and for both elbow flexion and shoulder
      abduction. CONCLUSION: FM patients exhibit an altered neuromuscular strategy for
      upper limb position control compared to HCs. The predominance of low-frequency
      limb oscillations among FM patients may indicate a sensory deficit.

PMID- 23006675
TI  - The TSC1-TSC2 complex consists of multiple TSC1 and TSC2 subunits.
AB  - BACKGROUND: Mutations to the TSC1 and TSC2 genes cause the disease tuberous
      sclerosis complex. The TSC1 and TSC2 gene products form a protein complex that
      integrates multiple metabolic signals to regulate the activity of the target of
      rapamycin (TOR) complex 1 (TORC1) and thereby control cell growth. Here we
      investigate the quaternary structure of the TSC1-TSC2 complex by gel filtration
      and coimmunoprecipitation. RESULTS: TSC1 and TSC2 co-eluted in high molecular
      weight fractions by gel filtration. Coimmunoprecipitation of distinct tagged TSC1
      and TSC2 isoforms demonstrated that TSC1-TSC2 complexes contain multiple TSC1 and
      TSC2 subunits. CONCLUSIONS: TSC1 and TSC2 interact to form large complexes
      containing multiple TSC1 and TSC2 subunits.

PMID- 23006676
TI  - Syrinx exceptionally revealed by isolated bilateral Horner's syndrome.

PMID- 23006677
TI  - Analysis of the distribution of bacteria within urinary catheter biofilms using
      four different molecular techniques.
AB  - BACKGROUND: Most nosocomial urinary tract infections are associated with the long
      term use of urinary catheters. Such urinary catheter-associated infections are
      caused by bacteria that reside in biofilms. We determined the distribution of
      fastidious/nonculturable bacteria in biofilm of urinary catheters and evaluated
      the availability of concurrent applying various molecular techniques. METHODS:
      The biofilms were isolated from urinary catheters that had been installed in
      patients for 3 or 4 weeks and examined by the following 4 different 16S ribosomal
      RNA (rRNA) analysis techniques: capillary electrophoresis, terminal restriction
      fragment length polymorphism (T-RFLP), denaturing gradient gel electrophoresis
      (DGGE), and pyrosequencing. RESULTS: A total of 329 isolates was identified by
      capillary electrophoresis. The most common genera were Edwardsiella,
      Enterobacter, Escherichia, and Pseudomonas. A total of 32 bacterial strains was
      identified by T-RFLP. Escherichia, Pseudomonas, Enterobacter, Moraxella, Proteus,
      Serratia, and Yersinia were the most represented genera. Similarly, Escherichia,
      Pseudomonas, and Enterobacter were the most prevalent according to DGGE.
      Burkholderia, Corynebacterium, Achromobacter, Alcaligenes, Citrobacter,
      Stenotrophomonas, and Streptococcus were also detected. Escherichia and
      Pseudomonas were abundantly detected by pyrosequencing. Enterobacter,
      Bacteroides, Klebsiella, Corynebacterium were also seen. CONCLUSION: These 4
      techniques detected different kinds of bacteria, suggesting that the simultaneous
      application of multiple techniques is necessary to accurately detect
      fastidious/nonculturable bacteria. Because bacterial growth within urinary
      catheter biofilms may be associated with urinary tract infections, further
      comprehensive studies are required.

PMID- 23006679
TI  - Composite brains: toward a systems theory of neural reconstruction.
AB  - The results of uncontrolled, open-label clinical trials indicate that
      reconstructive cellular therapies have the capacity to produce meaningful
      functional improvements in patients with brain disorders. However, the
      transplantation of fetal cells has not progressed to viable best practice
      treatment for any brain disorder. A conceptual approach, referred to as the
      Repair Model, has served as a useful heuristic for initiating research in the
      field and guiding the development of new practices. Analysis of evidence for the
      treatment of Parkinson's disease indicates that recovery following neural
      grafting is a complex process influenced by factors beyond the replacement of
      neurons. An alternative approach, the Composite Brain Model, is outlined to
      address limitations of the Repair Model. A hierarchical, open-system model is
      proposed, which aims to track the interactions between the grafted cells, the
      host brain, and the environment. The Composite Brain Model emphasizes the
      importance of the interactions between the patient, their physical and social
      environment, and the provision of rehabilitation during recovery. It is proposed
      that the Composite Brain Model is useful in providing an alternative perspective
      for research, theory building, and practice.

PMID- 23006678
TI  - Applicability of major histocompatibility complex DRB1 alleles as markers to
      detect vertebrate hybridization: a case study from Iberian ibex * domestic goat
      in southern Spain.
AB  - BACKGROUND: Hybridization between closely related wild and domestic species is of
      great concern because it can alter the evolutionary integrity of the affected
      populations. The high allelic variability of Major Histocompatibility Complex
      (MHC) loci usually excludes them from being used in studies to detect
      hybridization events. However, if a) the parental species don't share alleles,
      and b) one of the parental species possesses an exceptionally low number of
      alleles (to facilitate analysis), then even MHC loci have the potential to detect
      hybrids. RESULTS: By genotyping the exon2 of the MHC class II DRB1 locus, we were
      able to detect hybridization between domestic goats (Capra hircus) and free
      ranging Iberian ibex (Capra pyrenaica hispanica) by molecular means. CONCLUSIONS:
      This is the first documentation of a Capra pyrenaica * Capra hircus
      hybridization, which presented us the opportunity to test the applicability of
      MHC loci as new, simple, cost-effective, and time-saving approach to detect
      hybridization between wild species and their domesticated relatives, thus adding
      value to MHC genes role in animal conservation and management.

PMID- 23006681
TI  - Neural autonomic modulation of the heart: a new tool for cardiac surgeons?

PMID- 23006680
TI  - Determinants of non- response to a second assessment of lifestyle factors and
      body weight in the EPIC-PANACEA study.
AB  - BACKGROUND: This paper discusses whether baseline demographic, socio-economic,
      health variables, length of follow-up and method of contacting the participants
      predict non-response to the invitation for a second assessment of lifestyle
      factors and body weight in the European multi-center EPIC-PANACEA study. METHODS:
      Over 500.000 participants from several centers in ten European countries
      recruited between 1992 and 2000 were contacted 2-11 years later to update data on
      lifestyle and body weight. Length of follow-up as well as the method of
      approaching differed between the collaborating study centers. Non-responders were
      compared with responders using multivariate logistic regression analyses.
      RESULTS: Overall response for the second assessment was high (81.6%). Compared to
      postal surveys, centers where the participants completed the questionnaire by
      phone attained a higher response. Response was also high in centers with a short
      follow-up period. Non-response was higher in participants who were male (odds
      ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90;
      2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of
      poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had
      either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06;
      1.10); especially >=30 kg/m2, 1.26 (1.23; 1.29)). CONCLUSIONS: Cohort studies may
      enhance cohort maintenance by paying particular attention to the subgroups that
      are most unlikely to respond and by an active recruitment strategy using
      telephone interviews.

PMID- 23006682
TI  - If this were my last speech, what would I say?

PMID- 23006683
TI  - Invited commentary.

PMID- 23006684
TI  - Invited commentary.

PMID- 23006685
TI  - Invited commentary.

PMID- 23006686
TI  - Blake drains: a novel method of chest drainage after extracardiac fontan
      operation with autologous pericardium.
AB  - BACKGROUND: Pleural effusions after Fontan palliation remain a cause of increased
      length of stay, cost, and morbidity. We report our experience with Blake drains
      (BDs) and the outpatient pediatric pleural drain pathway after Fontan operation.
      METHODS: A retrospective chart review was performed on all patients who underwent
      extracardiac lateral tunnel (ECLT) Fontan operation with pedicled autologous
      pericardium. Patients with prolonged pleural drainage were analyzed for
      predisposing factors. RESULTS: From March 1995 to December 2009, 162 patients (92
      male, 56.8%) underwent ECLT Fontan operation. The median age at the time of
      Fontan operation was 30.9 months; the median weight was 12.9 kg. The median
      hospital stay was 4 days, and the median pleural drain requirement was 13 days.
      Prolonged pleural effusions occurred in 59 patients (36.4%), with prolonged
      cardiopulmonary bypass time identified as the only significant risk factor
      (p=0.04). Sixty patients (37%) were readmitted within 30 days of operation, with
      effusion requiring additional pleural drainage (n=41, 68.3%), infection (n=8,
      13.3%), or a combination of the two (n=3, 5%) being the most common reason. There
      were two early deaths, neither of which was associated with BD malfunction. The
      BD clinical pathway for ECLT Fontan operation reduced our institutional cost to
      about $38,000 per patient, which represents a significant savings compared with
      traditional management with extended hospital stay after Fontan operation.
      CONCLUSIONS: Silicone BDs are safe and effective after ECLT Fontan operation.
      Hospital length of stay and cost can be significantly decreased when these drains
      are used with appropriate family involvement and close outpatient surveillance.

PMID- 23006687
TI  - Bronchial stump aspergillosis after stapled lobectomy for lung cancer.
AB  - Aspergillus causes several pulmonary complications, but bronchial stump
      aspergillosis (BSA) is very rare. To date, 31 cases of bronchial stump
      aspergillosis have been reported in the English, German, and Japanese literature.
      The bronchial stump was closed by hand-sewn suturing in most cases, but we report
      herein two cases of BSA that developed after stapled closure of the bronchial
      stump.

PMID- 23006688
TI  - Cancer of the left lung with persistent left superior vena cava.
AB  - As operations for lung cancer become more common, more anomalies of various
      pulmonary arteries and veins are being encountered. Persistent left superior vena
      cava (PLSVC) is caused by abnormal development of the sinus venosus in early
      fetal life. In cases of PLSVC with left lung cancer, particular care must be
      exercised during the excision of the pulmonary vein, focusing on the region into
      which the PLSVC flows. In such anomalous cases, proper excision of the pulmonary
      artery and vein and lymph node dissection require a firm grasp of anatomic detail
      using preoperative computed tomographic scanning.

PMID- 23006689
TI  - Modified Tikhoff-Linberg procedure for posterior chest wall sarcoma.
AB  - The Tikhoff-Linberg procedure was originally described more than 80 years ago as
      a limb-sparing surgical option for malignancies involving the shoulder girdle.
      However, involvement of the chest wall was a contraindication, consigning
      patients to either amputation or shoulder disarticulation. With the addition of
      prosthetic and autologous tissue reconstruction of the chest wall, this procedure
      is a viable option for an extended group of patients. The modified procedure
      offers an excellent functional result, leaving the patient with a fully
      functional arm and hand.

PMID- 23006690
TI  - Giant esophageal diverticula after laparoscopic band placement.
AB  - An esophageal diverticulum is seen in a variety of gastroesophageal conditions,
      with most having an underlying motility disorder. The diverticulum is diagnosed
      by combining the patient's history, physical examination, computed tomographic
      chest scan, and barium radiography. We present an unusual case of a 43-year-old
      patient with a history of leiomyoma resection of the esophagus and an ensuing
      placement of a laparoscopic band for weight loss. One year after banding,
      persistent dysphagia led to the diagnosis of a large esophageal diverticulum. We
      believe that this esophageal diverticulum is the largest reported secondary to a
      laparoscopic band.

PMID- 23006691
TI  - Chronic sternum wound infection caused by Mycobacterium tuberculosis after
      cardiac surgery.
AB  - The sternum wound infection, caused by Mycobacterium tuberculosis after a cardiac
      surgery, is an extremely rare postoperative complication. It requires a high
      degree of suspicion for a correct diagnosis. Often a successful treatment is
      impeded by the insidious nature of tuberculosis infection and the time-consuming
      diagnosis process. We report two cases in which we successfully treated this
      infection with sternum resection, wound debridement, and antituberculosis
      medication.

PMID- 23006692
TI  - Arterial chimney graft cannulation for interventional lung assist.
AB  - An interventional lung assist membrane ventilator (iLA) for arteriovenous
      extracorporeal CO2 removal was connected to a small-diameter femoral artery by
      use of a chimney graft in an underweight patient with acute respiratory failure
      and a previous history of heart-lung transplantation. This concept offers
      additional therapeutic options in underweight patients requiring extracorporeal
      CO2 removal with arterial vessels that are too small for percutaneous arterial
      cannulation with standard-sized percutaneous insertable iLA cannulae.

PMID- 23006693
TI  - Ascending aortic graft thrombosis and diffuse embolization from early endoluminal
      Aspergillus infection.
AB  - We present a 43-year-old man who underwent emergent replacement of the ascending
      aorta for type A dissection and hemiarch reconstruction with a 28-mm prosthetic
      graft. Dramatic neurologic symptoms, renal failure, and bowel ischemia developed
      on postoperative day 5. A computed tomography scan showed a large floating
      thrombus in the ascending aortic graft and massive peripheral embolization
      throughout the body.

PMID- 23006694
TI  - Pulmonary pseudoaneurysm: uncommon complication after total aortic arch
      operation.
AB  - Pulmonary pseudoaneurysms are an uncommon but life-threatening condition of
      congenital or acquired cause, most commonly involving the branch pulmonary
      arteries and generally requiring emergent intervention. We describe a case of
      postoperative main pulmonary artery pseudoaneurysm after a complex aortic arch
      procedure, in which thoracic computed tomography provided full information for
      its definition before surgical correction.

PMID- 23006695
TI  - Nonoperative management of blunt traumatic cardiac rupture: considerations of a
      novel approach.
AB  - Blunt traumatic cardiac rupture carries a dismal prognosis. Patients who survive
      to presentation are treated with prompt surgical repair. Operative intervention
      carries significant morbidity and mortality, as these patients present in
      extremis. Intervention can be complicated by prior cardiac surgery. Obliteration
      of the pericardial space from adhesions may offer the patient an alternative
      conservative option under rare circumstances. We present a case of an older man
      with blunt cardiac rupture caused by a motor vehicle crash. The patient remained
      hemodynamically stable as his rupture only communicated with a small space within
      his obliterated pericardial sac. He was managed nonoperatively.

PMID- 23006696
TI  - Contained rupture of a pseudoaneurysm of the descending thoracic aorta related to
      remnant outflow graft of left ventricular assist device after heart
      transplantation.
AB  - The Jarvik 2000 left ventricular assist device is inserted via a left thoracotomy
      with the outflow graft anastomosed to the descending thoracic aorta. Removal of
      the device during heart transplantation involves division of the outflow graft,
      resulting in a retained remnant. We describe the first reported case of a mycotic
      pseudoaneurysm of the descending thoracic aorta related to the remnant of a left
      ventricular assist device outflow graft in an immunosuppressed heart recipient
      complicated with systemic Pseudomonas infection. The pseudoaneurysm was
      temporarily treated with endovascular stent grafting followed by delayed
      thoracotomy, pseudoaneurysm excision, and placement of an aortic interposition
      graft using an aortic allograft.

PMID- 23006697
TI  - Mitral valve surgery in a patient with systemic artery-to-pulmonary artery
      fistulas.
AB  - We report the case of a 68-year-old woman with severe mitral valve regurgitation
      and concomitant multiple systemic artery-to-pulmonary artery fistulas.
      Endovascular embolization of the fistulas was unable to control her heart
      failure, and mitral valve replacement was also performed. Steps were taken during
      mitral valve surgery to ensure an adequate operative field in the left atrium,
      despite the large volume of in-pouring blood from the pulmonary vein.

PMID- 23006698
TI  - Troubleshooting in transatrial tricuspid valve-in-valve implantation.
AB  - The established treatment for degenerated stenotic tricuspid bioprostheses is
      reoperation. Recently, transcatheter tricuspid valve implantation has been
      reported as an alternative option. This case report describes a complex
      transcatheter tricuspid valve implantation in a degenerated Medtronic intact 31
      mm bioprosthesis. Implantation of a 26 mm Edwards Sapien valve failed, subsequent
      transcatheter implantation of a 29 mm Edwards Sapien valve was successful.

PMID- 23006699
TI  - Unsuspected finding of a relapsing perichondritis during lung explantation.

PMID- 23006700
TI  - Partial anomalous venous return of left superior pulmonary vein in adult.

PMID- 23006701
TI  - External tracheal stabilization technique for acquired tracheomalacia using a
      tailored silicone tube.
AB  - Here, we describe an external tracheal stabilization technique used in a patient
      with tracheomalacia. A 56-year-old man presented with tracheomalacia due to
      prolonged mechanical ventilation. The malacic tracheal segment was approximately
      2 cm in length. The malacic segment was covered with a silicone tube sutured in
      place using Prolene sutures (Ethicon, Somerville, NJ). Several anchoring sutures
      were placed between the tracheal mucosa and the silicone tube without violating
      the mucosal continuity. The patient was discharged on postoperative day 5 without
      complication. This method of external tracheal stabilization is a less invasive
      alternative for the management of this particular patient.

PMID- 23006702
TI  - Cabled butterfly closure: a novel technique for sternal closure.
AB  - Impaired sternal wound healing remains problematic after median sternotomy and
      can lead to significant morbidity after cardiac surgical procedures. Although
      metal plating systems exist for closing the sternum, their use is limited by
      expense and practicality, and simple wire closure remains the most common
      technique to close the sternum. We describe a cabling technique for sternal
      closure that is secure, uses standard sternal wire, and may be used on every
      patient. We have used the technique routinely in 291 patients with no sternal
      dehiscence or wound healing problems.

PMID- 23006703
TI  - Surgical repair of aberrant subclavian artery through clamshell approach.
AB  - Aberrant subclavian artery is a rare abnormality that often occurs in association
      with Kommerell's diverticulum. The optimal surgical treatment is exclusion and
      reconstruction of the dilated diverticulum or aberrant subclavian artery. To
      accomplish such a radical operation in a single stage, we have introduced total
      (or partial) arch replacement using deep hypothermic circulatory arrest and the
      arch-first technique through a bilateral submammary thoracotomy (the clamshell
      approach). This technique provides excellent exposure of the neck arteries and
      the entire thoracic aorta.

PMID- 23006704
TI  - Protecting the infant brain during cardiac surgery: a systematic review.
AB  - Prevention of brain injury during congenital heart surgery has focused on
      intraoperative and perioperative neuroprotection and neuromonitoring. Many
      strategies have been adopted as "standard of care." However, the strength of
      evidence for these practices and the relationship to long-term outcomes are
      unknown. We performed a systematic review (January 1, 1990 to July 30, 2010) of
      neuromonitoring and neuroprotection strategies during cardiopulmonary bypass
      (CPB) in infants of age 1 year or less. Papers were graded individually and as
      thematic groups, assigning evidence-based medicine and American College of
      Cardiology/American Heart Association (ACC/AHA) level of evidence grades.
      Consensus scores were determined by adjudication. Literature search identified
      527 manuscripts; 162 met inclusion criteria. Study designs were prospective
      observational cohort (53.7%), case-control (21.6%), randomized clinical trial
      (13%), and retrospective observational cohort (9.9%). Median sample size was 43
      (range 3 to 2,481). Primary outcome was evidence of structural brain injury or
      functional disability (neuroimaging, electroencephalogram, formal neurologic
      examination, or neurodevelopmental testing) in 43%. Follow-up information was
      reported in only 29%. The most frequent level of evidence was evidence-based
      medicine level 4 (33.3%) or ACC/AHA class IIB: level B (42%). The only
      intervention with sufficient evidence to recommend "the procedure or treatment
      should be performed" was avoidance of extreme hemodilution during CPB. Data
      supporting use of current neuromonitoring and neuroprotective techniques are
      limited. The level of evidence is insufficient to support effectiveness of most
      of these strategies. Well-designed studies with correlation to clinical outcomes
      and long-term follow-up are needed to develop guidelines for neuromonitoring and
      neuroprotection during CPB in infants.

PMID- 23006705
TI  - Integrated thoracic residency: the only pathway of thoracic surgery training in
      the future?

PMID- 23006706
TI  - Impact of neoadjuvant chemoradiation in early esophageal cancers.

PMID- 23006708
TI  - Late surgical conversion and inappropriate indications for TEVAR.

PMID- 23006709
TI  - Advancing the management of acute type A aortic dissection.

PMID- 23006710
TI  - Dissecting thoracic aortic aneurysms.

PMID- 23006713
TI  - Additional venting for poor venous drainage.

PMID- 23006715
TI  - Three-dimensional transesophageal echocardiography of a thrombus entrapped by a
      patent foramen ovale.
AB  - The substrate of paradoxic embolization is a patent foramen ovale allowing right
      to-left passage of embolic material. A thrombus in transit entrapped by a patent
      foramen straddling an atrial septal aneurysm is an exceedingly transient
      condition rarely documented on imaging studies. We present the case of a 67-year
      old man with acute pulmonary embolism and concomitant cerebral infarction found
      to have a large thrombus traversing a patent foramen ovale. Intraoperative real
      time three-dimensional transesophageal echocardiography allowed accurate spatial
      characterization of the thrombus and correlated closely with surgical findings.
      It provided more realistic intraoperative guidance compared with conventional two
      dimensional transesophageal echocardiography.

PMID- 23006716
TI  - Rare combination of dextrocardia with right-sided Poland syndrome.
AB  - The combination of right-sided Poland syndrome and dextrocardia is rare. To our
      knowledge, reports regarding this subject are lacking in the published literature
      to date. Previous reports suggested that dextrocardia may be part of the left
      sided Poland syndrome. We report and discuss this rare combination.

PMID- 23006717
TI  - Intracardiac Wegener's granulomatosis.

PMID- 23006718
TI  - Anomalous origin of left pulmonary artery from left subclavian artery.

PMID- 23006719
TI  - The use of biomaterials for chest wall reconstruction 30 years after radical
      surgery and radiation.
AB  - The combination of titanium plates and acellular collagen matrix was used to
      restore anterior chest wall integrity in a 68-year-old woman more than 30 years
      after a Halsted mastectomy and radiation treatment. A vertical rectus abdominis
      muscle flap was used for myocutaneous coverage of the reconstructed chest wall.
      Partial necrosis of the flap caused prolonged exposure of the collagen matrix and
      the titanium plates, which were then covered with a free skin graft. Long-term
      results were satisfactory despite continued infection treated with vacuum
      assisted closure and surgical debridement. Recently introduced materials for
      chest wall reconstruction may offer resilience to infection, tolerability, and
      stability, and their use may be contemplated when the potential for local
      morbidity is high.

PMID- 23006720
TI  - Paraesophageal hernia repair followed by cardiac tamponade caused by ProTacks.
AB  - We describe a case of cardiac tamponade caused by ProTacks Autosuture used for
      mesh fixation during a laparoscopic Nissen operation with giant paraesophageal
      hernia repair. Perforations of the posterior descendent artery and epicardial
      vein of the right ventricle were caused by ProTacks used for Parietex Composite
      Mesh fixation. Protruding ProTacks were secured from inside the pericardiac sac
      with a synthetic vascular patch during emergency sternotomy. Quick and
      multidisciplinary cooperation ended with emergency cardiothoracic procedure
      saving the patient's life and preventing further damage to the heart muscle and
      its vessels.

PMID- 23006721
TI  - Surgical repair of a left atrial-esophageal fistula after radiofrequency catheter
      ablation for atrial fibrillation.
AB  - Left atrial-esophageal fistula is a highly lethal complication of ablative
      therapy for atrial fibrillation. Because of its unusual rate of occurrence, there
      has not been a uniform approach to either the diagnosis or corrective therapy. We
      offer 1 such surgical option based on presumptive and early diagnosis-left atrial
      repair with cardiopulmonary bypass followed by repair of the esophagus with an
      omental wrap and supported with decompressive gastrostomy and feeding
      jejunostomy.

PMID- 23006722
TI  - Percutaneous aortic valve replacement using a subclavian artery graft.
AB  - Over the past few years transcatheter heart valve implantation (THI) has become
      an alternative treatment for aortic valve replacement. The THI does not require a
      midline sternotomy or cardiopulmonary bypass and can be performed through a
      transfemoral or a transapical approach. In case of severe peripheral vascular
      disease the transapical route is usually chosen. However, when the use of a small
      anterolateral thoracotomy is not preferred due to comorbidities, the subclavian
      artery can be considered as a third alternative route. This case report describes
      an approach for THI through the subclavian artery, by using a Dacron graft.

PMID- 23006723
TI  - Modification of a stented bovine jugular vein conduit (melody valve) for surgical
      mitral valve replacement.
AB  - We report the use of a Melody valve as a surgical implant in the mitral position
      in 2 infants, one with severe mitral regurgitation and another with mitral
      stenosis, where other prostheses are not small enough to be implanted in the
      mitral position nor expandable as the child grows.

PMID- 23006724
TI  - Cone reconstruction of Ebstein's anomaly in a neonate.
AB  - Neonatal repair of Ebstein's anomaly is challenging and should be considered only
      if medical measures to stabilize the circulation and provide antegrade pulmonary
      blood flow fail. Anatomic repair, based on the cone reconstruction technique, has
      demonstrated promising survival benefits in older patients; however, there are no
      data regarding neonatal repair. This is a report on a successful salvage
      operation using cone reconstruction of Ebstein's anomaly in a neonate who had
      required extracorporeal membrane oxygenation support before surgery and who had
      failed to wean.

PMID- 23006725
TI  - Characterization of a midgut-specific chitin synthase gene (LmCHS2) responsible
      for biosynthesis of chitin of peritrophic matrix in Locusta migratoria.
AB  - Chitin, an essential component of peritrophic matrix (PM), is produced by a
      series of biochemical reactions. Chitin synthase plays a crucial role in chitin
      polymerization in chitin biosynthetic pathway. In this study, we identified and
      characterized a full-length cDNA of chitin synthase 2 gene (LmCHS2) from Locusta
      migratoria. The cDNA contains an open reading frame of 4569 nucleotides that
      encode 1523 amino acid residues, and 76- and 373-nucleotides for 5'- and 3'
      noncoding regions, respectively. Analysis of LmCHS2 transcript in different
      tissues of the locust by using real-time quantitative PCR indicated that LmCHS2
      was exclusively expressed in midgut and gastric caeca (a part of the midgut). The
      highest expression was found in the anterior midgut with a decline of the
      transcript level from the anterior to posterior regions. During growth and
      development of locusts, there was only a slight expression in eggs, but the
      expression gradually increased from nymphs to adults. In situ hybridization
      further revealed that LmCHS2 transcript mainly presented in the apical regions of
      brush border forming columnar cells of gastric caeca. LmCHS2 dsRNA was injected
      to fifth-instar nymphs to further explore biological functions of LmCHS2.
      Significantly down-regulated transcript of LmCHS2 resulted in a cessation of
      feeding and a high mortality of the insect. However, no visible abnormal
      morphological change of locusts was observed until insects molted to adults.
      After dissection, we found that the average length of midguts from the LmCHS2
      dsRNA-injected locusts was shorter than that of the control insects that were
      injected with dsGFP. Furthermore, microsection of midguts showed that the PM of
      the LmCHS2 dsRNA-injected nymphs was amorphous and thin as compared with the
      controls. Our results demonstrate that LmCHS2 is responsible for the biosynthesis
      of chitin associated with PM and plays an essential role in locust growth and
      development.

PMID- 23006726
TI  - Effect of a single bolus injection of low-dose hydrocortisone for prevention of
      atrial fibrillation recurrence after radiofrequency catheter ablation.
AB  - BACKGROUND: The transient use of corticosteroid shortly after atrial fibrillation
      (AF) ablation might prevent immediate and mid-term AF recurrence; however, the
      effective dosage for preventing AF recurrence has not been determined. In this
      study, we evaluated whether low-dose hydrocortisone is effective for the
      prevention of AF recurrence after radiofrequency catheter ablation (RFCA).
      METHODS AND RESULTS: We enrolled 89 AF patients (70 males, 55.8 +/- 10.9 years)
      who underwent RF ablation and were treated with single bolus injection of 100mg
      hydrocorticosteroid (corticosteroid group). For the control group, we enrolled
      120 sex- and age-matched AF patients (94 males, 55.4 +/- 10.5 years).
      Pericarditis occurred in 3 (2.5%) and 1 (1.1%) patients in the control and
      corticosteroid groups, respectively. The number of patients with immediate AF
      recurrence (<= 2 days) was 17 (14.5%) and 11 (12.4%) in the control and steroid
      groups, respectively (P=0.687). Treatment with low-dose steroid did not decrease
      early (3-30 days) AF recurrence (13 [11.1%] vs. 11 [12.5%], P=0.829) or late (>=
      31 days) AF recurrence after ablation (26 [22.2%] vs. 13 [14.6%], P=0.209). There
      was no difference in cumulative survival free of late AF recurrence between the
      corticosteroid and control groups (P=0.57 by log-rank test). White blood cell
      count, C-reactive protein concentration and maximum body temperature also were
      unchanged by low-dose steroid. CONCLUSIONS: Single bolus injection of low-dose
      hydrocortisone after AF ablation is not effective for preventing AF recurrence
      during the mid-term follow-up period.

PMID- 23006727
TI  - Effects of parental hypertension on longitudinal trends in blood pressure and
      plasma metabolic profile: mixed-effects model analysis.
AB  - The mechanism underlying the association of parental hypertension with
      cardiovascular events in offspring remains unclear. In this study, the effects of
      parental hypertension on longitudinal trends of blood pressure and metabolic
      parameters were examined by mixed-effects model analysis. From 1977 to 2006, 5198
      subjects participated in the Tanno-Sobetsu Study, and we selected 2607 subjects
      (1095 men and 1512 women) for whom data on parental history of hypertension were
      available. In both men and women with and without parental hypertension, systolic
      blood pressure and fasting blood glucose levels consistently increased from the
      third to eighth decades of life, whereas diastolic blood pressure and serum
      triglyceride levels followed biphasic (inverted U shape) time courses during that
      period. However, the relationships between the parameters and age were
      significantly shifted upward (by ~5.3 mm Hg in systolic blood pressure, 2.8 mm Hg
      in diastolic blood pressure, 0.30 mmol/L in blood glucose, and 0.09 mmol/L in
      triglyceride) in the group with parental hypertension compared with those in the
      group without parental hypertension. Both paternal and maternal histories of
      hypertension were determinants of systolic blood pressure and diastolic blood
      pressure, and there was no significant interaction between the sides of parental
      history. There were no significant effects of parental hypertension on age
      dependent or body mass index-dependent changes in serum low-density lipoprotein
      cholesterol or high-density lipoprotein cholesterol level. The present results
      indicate that parental hypertension has an age-independent impact on elevation of
      blood pressure, plasma glucose, and triglyceride levels, which may underlie the
      reported increase in cardiovascular events by family history of hypertension.

PMID- 23006728
TI  - Decrease of intracellular chloride concentration promotes endothelial cell
      inflammation by activating nuclear factor-kappaB pathway.
AB  - Recent evidence suggested that ClC-3 channel/antiporter is involved in regulation
      of nuclear factor (NF)-kappaB activation. However, the mechanism explaining how
      ClC-3 modulates NF-kappaB signaling is not well understood. We hypothesized that
      ClC-3-dependent alteration of intracellular chloride concentration ([Cl(-)](i))
      underlies the effect of ClC-3 on NF-kappaB activity in endothelial cells. Here,
      we found that reduction of [Cl(-)](i) increased tumor necrosis factor-alpha
      (TNFalpha)-induced expression of intercellular adhesion molecule 1 and vascular
      cell adhesion molecule 1 and adhesion of monocytes to endothelial cells (P<0.05;
      n=6). In Cl(-) reduced solutions, TNFalpha-evoked IkappaB kinase complex beta and
      inhibitors of kappaBalpha phosphorylation, inhibitors of kappaBalpha degradation,
      and NF-kappaB nuclear translocation were enhanced. In addition, TNFalpha and
      interleukin 1beta could activate an outward rectifying Cl(-) current in human
      umbilical vein endothelial cells and mouse aortic endothelial cells. Knockdown or
      genetic deletion of ClC-3 inhibited or abolished this Cl(-) conductance.
      Moreover, Cl(-) channel blockers, ClC-3 knockdown or knockout remarkably reduced
      TNFalpha-induced intercellular adhesion molecule 1 and vascular cell adhesion
      molecule 1expression, monocytes to endothelial cell adhesion, and NF-kappaB
      activation (P<0.01; n=6). Furthermore, TNFalpha-induced vascular inflammation and
      neutrophil infiltration into the lung and liver were obviously attenuated in ClC
      3 knockout mice (P<0.01; n=7). Our results demonstrated that decrease of [Cl(
      )](i) induced by ClC-3-dependent Cl(-) efflux promotes NF-kappaB activation and
      thus potentiates TNFalpha-induced vascular inflammation, suggesting that
      inhibition of ClC-3-dependent Cl(-) current or modification of intracellular Cl(
      ) content may be a novel therapeutic approach for inflammatory diseases.

PMID- 23006729
TI  - Hyperuricemia and hypertension: a confluence of concepts.

PMID- 23006730
TI  - Preeclampsia is characterized by placental complement dysregulation.
AB  - Increasing evidence suggests that preeclampsia is associated with complement
      dysregulation. The origin of complement dysregulation in preeclampsia is unknown,
      and further unraveling this mechanism could provide both diagnostic tools and
      therapeutic targets. Because the placenta is believed to play a crucial role in
      the pathogenesis of preeclampsia, we investigated placentas from preeclamptic
      women (n=28) and controls (n=44) for the presence of complement activation
      products. Immunohistochemistry was performed for C1q, mannose-binding lectin,
      properdin, and C4d. Staining patterns were related to pregnancy outcome. Possible
      causes of complement activation were investigated, including the presence of
      immune deposits at the syncytiotrophoblast and changes in the placental mRNA
      expression of complement regulatory proteins. C4d was rarely present in placentas
      from healthy controls (3%), whereas it was observed in 50% of placentas obtained
      from preeclamptic women (P=0.001). In these placentas, C4d was observed in a
      focal (9/14) or diffuse (5/14) staining pattern at the syncytiotrophoblast. With
      respect to C1q, mannose-binding lectin, and properdin, no differences were
      observed between cases and controls. In preeclamptic women, diffuse placental C4d
      was associated with a significantly lower gestational age at delivery.
      Furthermore, the mRNA expression of the complement regulatory proteins CD55 and
      CD59 was significantly upregulated in preeclampsia. In conclusion, there is
      evidence for increased classical pathway activation and altered complement
      regulation in preeclampsia. The relation between C4d and lower gestational age at
      birth suggests that the extent of complement dysregulation is associated with the
      severity of preeclampsia. Inhibiting excessive complement activation may be a
      promising therapeutic approach in the management of preeclampsia.

PMID- 23006732
TI  - Making good use of diastolic and systolic blood pressures in the management of
      hypertension.

PMID- 23006731
TI  - Impact of age on the importance of systolic and diastolic blood pressures for
      stroke risk: the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM)
      Project.
AB  - This study investigates age-related shifts in the relative importance of systolic
      (SBP) and diastolic (DBP) blood pressures as predictors of stroke and whether
      these relations are influenced by other cardiovascular risk factors. Using 34
      European cohorts from the MOnica, Risk, Genetics, Archiving, and Monograph
      (MORGAM) Project with baseline between 1982 and 1997, 68 551 subjects aged 19 to
      78 years, without cardiovascular disease and not receiving antihypertensive
      treatment, were included. During a mean of 13.2 years of follow-up, stroke
      incidence was 2.8%. Stroke risk was analyzed using hazard ratios per 10-mm Hg/5
      mm Hg increase in SBP/DBP by multivariate-adjusted Cox regressions, including SBP
      and DBP simultaneously. Because of nonlinearity, DBP was analyzed separately for
      DBP >= 71 mm Hg and DBP <71 mm Hg. Stroke risk was associated positively with SBP
      and DBP >= 71 mm Hg (SBP/DBP >= 71 mm Hg; hazard ratios: 1.15/1.06 [95% CI: 1.12
      1.18/1.03-1.09]) and negatively with DBP <71 mm Hg (0.88[0.79-0.98]). The hazard
      ratio for DBP decreased with age (P<0.001) and was not influenced by other
      cardiovascular risk factors. Taking into account the age * DBP interaction, both
      SBP and DBP >= 71 mm Hg were significantly associated with stroke risk until age
      62 years, but in subjects older than 46 years the superiority of SBP for stroke
      risk exceeded that of DBP >= 71 mm Hg and remained significant until age 78
      years. DBP <71 mm Hg became significant at age 50 years with an inverse relation
      to stroke risk. In Europeans, stroke risk should be assessed by both SBP and DBP
      until age 62 years with increased focus on SBP from age 47 years. From age 62
      years, emphasis should be on SBP without neglecting the potential harm of very
      low DBP.

PMID- 23006733
TI  - Calpain-1 regulation of matrix metalloproteinase 2 activity in vascular smooth
      muscle cells facilitates age-associated aortic wall calcification and fibrosis.
AB  - Age-associated central arterial wall stiffness is linked to extracellular matrix
      remodeling, including fibrosis and vascular calcification. Angiotensin II induces
      both matrix metalloproteinase 2 (MMP2) and calpain-1 expression and activity in
      the arterial wall. However, the role of calpain-1 in MMP2 activation and
      extracellular matrix remodeling remains unknown. Dual histo-immunolabeling
      demonstrates colocalization of calpain-1 and MMP2 within old rat vascular smooth
      muscle cells. Overexpression of calpain-1 induces MMP2 transcripts, protein
      levels, and activity, in part, by increasing the ratio of membrane type 1 MMPs to
      tissue inhibitor of metalloproteinases 2. These effects of calpain-1
      overexpression-induced MMP2 activation are linked to increased collagen I and III
      production and vascular calcification. In addition, overexpression of calpain-1
      also induces transforming growth factor-beta1/Smad signaling, elastin
      degradation, alkaline phosphatase activation, and total calcium content but
      reduces the expression of calcification inhibitors, osteopontin, and osteonectin,
      in cultured vascular smooth muscle cells in vitro and in carotid artery rings ex
      vivo. Furthermore, both calpain-1 and collagen II increase with aging within
      human aortic intima. Interestingly, in aged human aortic wall, both calpain-1 and
      collagen II are highly expressed in artherosclerotic plaque areas compared with
      grossly normal areas. Cross-talk of 2 proteases, calpain-1 and MMP2, leads to
      secretion of active MMP2, which modulates extracellular matrix remodeling via
      enhancing collagen production and facilitating vascular calcification. These
      results establish calpain-1 as a novel molecular candidate to retard age
      associated extracellular matrix remodeling and its attendant risk for
      hypertension and atherosclerosis.

PMID- 23006734
TI  - cGMP-dependent activation of protein kinase G precludes disulfide activation:
      implications for blood pressure control.
AB  - Protein kinase G (PKG) is activated by nitric oxide (NO)-induced cGMP binding or
      alternatively by oxidant-induced interprotein disulfide formation. We found
      preactivation with cGMP attenuated PKG oxidation. 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ) blockade of cGMP production increased disulfide PKG to
      13 +/- 2% and 29+/-4% of total in aorta and mesenteries, respectively. This was
      potentially anomalous, because we observed 2.7-fold higher NO levels in aorta
      than mesenteries; consequently, we had anticipated that ODQ would induce more
      disulfide in the conduit vessel. ODQ also constricted aorta, whereas it had no
      effect on mesenteries. Thus, mesenteries, but not aorta, can compensate for loss
      of NO-cGMP by recruiting disulfide activation of PKG. Mechanistically, this is
      explained by loss of cGMP allowing disulfide formation in response to basal
      oxidant production. Why aorta treated with ODQ generated less PKG disulfide that
      is insufficient to induce vasoconstriction was unclear. One potential
      explanation, especially because aorta were much less sensitive than mesenteries
      to exogenous H(2)O(2)-induced relaxation (EC(50)=205 +/- 24 and 33 +/- 2 umol/L,
      respectively) was that conduit vessels may have higher peroxidase capacity.
      Indeed, we found that aorta express 49 +/- 22% and 80 +/- 25% more peroxiredoxin
      and thioredoxin, respectively, than mesenteries, and their 2-Cys peroxiredoxin
      peroxidatic cysteines were also less sensitive to hyperoxidation. The higher
      peroxidase capacity of aortas would explain their constriction during cGMP
      removal and their insensitivity to H(2)O(2)-induced relaxation compared with
      mesenteries. In summary, cGMP binding to PKG induces a state that is resistant to
      disulfide formation. Consequently, cGMP depletion sensitizes PKG to oxidation;
      this happens to a lesser extent in aortas than in mesenteries, because the
      conduit vessels generate more NO and express more peroxiredoxin.

PMID- 23006736
TI  - Uric acid reduction rectifies prehypertension in obese adolescents.
AB  - Epidemiologic studies, animal models, and preliminary clinical trials in children
      implicate uric acid in the development of essential hypertension. Controversy
      remains as to whether the observations indicate a general mechanism or a
      surrogate phenomenon. We sought to determine whether uric acid is a causative
      mediator of increased blood pressure (BP) and impaired vascular compliance. We
      report a randomized, double-blinded, placebo-controlled trial comparing 2
      mechanisms of urate reduction with placebo in prehypertensive, obese,
      adolescents, aged 11 to 17 years. Subjects were randomized to the xanthine
      oxidase inhibitor, allopurinol, uricosuric, probenecid, or placebo. Subjects
      treated with urate-lowering therapy experienced a highly significant reduction in
      BP. In clinic systolic BP fell 10.2 mm Hg and diastolic BP fell 9.0 mm Hg in
      treated patients compared with a rise of 1.7 mm Hg and 1.6 mm Hg systolic and
      diastolic BP, respectively in patients on placebo. Urate-lowering therapy also
      resulted in significant reduction in systemic vascular resistance. These data
      indicate that, at least in adolescents with prehypertension, uric acid causes
      increased BP that can be mitigated by urate lowering therapy.

PMID- 23006735
TI  - EP1 disruption attenuates end-organ damage in a mouse model of hypertension.
AB  - Prostaglandin E(2) is a major prostanoid found in the kidney and vasculature
      contributing to the regulation of blood pressure. The prostaglandin E(2) receptor
      EP1 has been shown to contribute to hypertension by mediating angiotensin II
      dependent vasoconstriction, although its precise role is incompletely
      characterized. Disruption of the EP1 receptor in C57BL/6J mice reduced the
      incidence of mortality during severe hypertension induced by uninephrectomy,
      deoxycorticosterone acetate, and angiotensin II. Mortality was dependent on all
      components of the model. Death was a result of aortic aneurysm rupture or
      occurred after development of anasarca, each of which was reduced in EP1-/- mice.
      Mean arterial pressure was increased in treated EP1+/+ and EP1-/- mice; however,
      this elevation was significantly lower in EP1-/- mice. Blood pressure reduction
      via administration of hydralazine phenocopied EP1-/- mice. Thus, reduction in
      blood pressure by disruption of EP1 reduced incidence of mortality and decreased
      organ damage, suggesting that EP1 receptor blockade may be a viable target for
      antihypertensive therapy.

PMID- 23006737
TI  - Complement activation in pregnancy: too much of a good thing?

PMID- 23006738
TI  - The legal guardians' dilemma: Decision making associated with invasive non-life
      saving procedures.
AB  - BACKGROUND: ICU patients frequently undergo non-life-saving invasive procedures.
      When patient informed consent cannot be obtained, legal guardianship (LG), often
      from a close relative, may be required by law. The objective of this cohort study
      was to investigate the attitudes of LGs of ICU patients regarding the process of
      decision making for invasive non-life-saving procedures. METHODS: The study was
      conducted from May 2009 until June 2010 in general medical/surgical ICUs in two
      large Israeli medical centers. All 64 LGs who met the study criteria agreed to
      participate in the study. Three questionnaires were administered: a demographic
      data questionnaire, the Family Satisfaction with ICU 34 Questionnaire, and the
      Attitudes towards the LG Decision Making Process questionnaire, developed by the
      authors. RESULTS: The sample consisted of 64 LGs. Most participants were married
      (n = 56, 87.5%), male (n = 33, 51.6%), who had either a high school (n = 24,
      37.5%) or college (n = 19, 29.7%) education, and were at a mean age of 49.2 (+/
      11.22). Almost all of the procedures performed were tracheotomies (n = 63,
      98.4%). About two-thirds of the LGs preferred decisions to be made by the medical
      staff after discussing options with them (n = 42, 65.6%) and about three-fifths
      stated that decisions could be made without the need for the appointment of an LG
      (n = 37, 57.8%). Attitudes towards ease of obtaining information and honesty of
      information were more positive compared to those of consistency and understanding
      of information. CONCLUSIONS: The legal guardianship process requires better
      communication and more understandable information in order to assist LGs in
      making decisions for others in at times vague and stressful situations.

PMID- 23006739
TI  - The antitumor effect of GDC-0941 alone and in combination with rapamycin in
      breast cancer cells.
AB  - BACKGROUND: The phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of
      rapamycin (mTOR) pathway is a key potential target in breast cancer therapy.
      Because some cancer cell lines are resistant to mTOR inhibition, we combined the
      mTOR inhibitor with the PI3K inhibitor and assayed the inhibitory effect of this
      combination versus that of a single inhibitor. METHODS: The proliferation of
      MCF7, SK-BR-3, T-47D, and MDA-MB-231 cells was measured by MTT assay in the
      presence of GDC-0941 and/or rapamycin. Afterwards, we determined the visible
      changes in signaling in the PI3K/AKT/mTOR pathway by Western blotting. RESULTS:
      GDC-0941 exhibited excellent inhibition on MCF7, T-47D and SK-BR-3 cells with
      different characteristics. In addition, GDC-0941 blocked the feedback of PI3K/Akt
      through S6K1, resulting in decreased Akt activity by rapamycin activation. The
      combination of GDC-0941 and rapamycin downregulated the key components of the
      cell cycle machinery, such as cyclin D1 and upregulated the apoptotic markers.
      CONCLUSION: Our findings suggest that GDC-0941, either alone or in combination
      with rapamycin, may serve as a new, promising approach for breast cancer
      treatment.

PMID- 23006740
TI  - Structural insights from random mutagenesis of Campylobacter jejuni
      oligosaccharyltransferase PglB.
AB  - BACKGROUND: Protein glycosylation is of fundamental importance in many biological
      systems. The discovery of N-glycosylation in bacteria and the functional
      expression of the N-oligosaccharyltransferase PglB of Campylobacter jejuni in
      Escherichia coli enabled the production of engineered glycoproteins and the study
      of the underlying molecular mechanisms. A particularly promising application for
      protein glycosylation in recombinant bacteria is the production of potent
      conjugate vaccines where polysaccharide antigens of pathogenic bacteria are
      covalently bound to immunogenic carrier proteins. RESULTS: In this study capsular
      polysaccharides of the clinically relevant pathogen Staphylococcus aureus
      serotype 5 (CP5) were expressed in Escherichia coli and linked in vivo to a
      detoxified version of Pseudomonas aeruginosa exotoxin (EPA). We investigated
      which amino acids of the periplasmic domain of PglB are crucial for the
      glycosylation reaction using a newly established 96-well screening system
      enabling the relative quantification of glycoproteins by enzyme-linked
      immunosorbent assay. A random mutant library was generated by error-prone PCR and
      screened for inactivating amino acid substitutions. In addition to 15 inactive
      variants with amino acid changes within the previously known, strictly conserved
      WWDYG motif of N-oligosaccharyltransferases, 8 inactivating mutations mapped to a
      flexible loop in close vicinity of the amide nitrogen atom of the acceptor
      asparagine as revealed in the crystal structure of the homologous enzyme C. lari
      PglB. The importance of the conserved loop residue H479 for glycosylation was
      confirmed by site directed mutagenesis, while a change to alanine of the
      adjacent, non-conserved L480 had no effect. In addition, we investigated
      functional requirements in the so-called MIV motif of bacterial N
      oligosaccharyltransferases. Amino acid residues I571 and V575, which had been
      postulated to interact with the acceptor peptide, were subjected to cassette
      saturation mutagenesis. With the exception of I571C only hydrophobic residues
      were found in active variants. Variant I571V performed equally well as the wild
      type, cysteine at the same position reduced glycoprotein yield slightly, while a
      change to phenylalanine reduced activity by a factor of three. CONCLUSIONS: This
      study provides novel structure-function relationships for the periplasmic domain
      of the Campylobacter jejuni N-oligosaccharyltransferase PglB and describes
      procedures for generating and screening oligosaccharyltransferase mutant
      libraries in an engineered E. coli system.

PMID- 23006742
TI  - Walking school bus programs in U.S. public elementary schools.
AB  - BACKGROUND: Active transportation to school provides an important way for
      children to meet physical activity recommendations. The "walking school bus"
      (WSB) is a strategy whereby adults walk with a group of children to and from
      school along a fixed route. This study assessed whether school-organized WSB
      programs varied by school characteristics, district policies, and state laws.
      METHODS: School data were gathered by mail-back surveys in nationally
      representative samples of U.S. public elementary schools during the 2008-2009 and
      2009-2010 school years (n = 632 and 666, respectively). Corresponding district
      policies and state laws were obtained. RESULTS: Nationwide, 4.2% of schools
      organized a WSB program during 2008-2009, increasing to 6.2% by 2009-2010.
      Controlling for demographic covariates, schools were more likely to organize a
      WSB program where there was a strong district policy pertaining to safe active
      routes to school (OR = 2.14, P < .05), or a state law requiring crossing guards
      around schools (OR = 2.72, P < .05). CONCLUSIONS: WSB programs are not common but
      district policies and state laws are associated with an increased likelihood of
      elementary schools organizing these programs. Policymaking efforts may encourage
      schools to promote active transportation.

PMID- 23006741
TI  - Epitope mapping by random peptide phage display reveals essential residues for
      vaccinia extracellular enveloped virion spread.
AB  - BACKGROUND: A33 is a type II integral membrane protein expressed on the
      extracellular enveloped form of vaccinia virus (VACV). Passive transfer of A33
      directed monoclonal antibodies or vaccination with an A33 subunit vaccine confers
      protection against lethal poxvirus challenge in animal models. Homologs of A33
      are highly conserved among members of the Orthopoxvirus genus and are potential
      candidates for inclusion in vaccines or assays targeting extracellular enveloped
      virus activity. One monoclonal antibody directed against VACV A33, MAb-1G10, has
      been shown to target a conformation-dependent epitope. Interestingly, while it
      recognizes VACV A33 as well as the corresponding variola homolog, it does not
      bind to the monkeypox homolog. In this study, we utilized a random phage display
      library to investigate the epitope recognized by MAb-1G10 that is critical for
      facilitating cell-to-cell spread of the vaccinia virus. RESULTS: By screening
      with linear or conformational random phage libraries, we found that phages
      binding to MAb-1G10 display the consensus motif CEPLC, with a disulfide bond
      formed between two cysteine residues required for MAb-1G10 binding. Although the
      phage motif contained no linear sequences homologous to VACV A33, structure
      modeling and analysis suggested that residue D115 is important to form the
      minimal epitope core. A panel of point mutants expressing the ectodomain of A33
      protein was generated and analyzed by either binding assays such as ELISA and
      immunoprecipitation or a functional assessment by blocking MAb-1G10 mediated
      comet inhibition in cell culture. CONCLUSIONS: These results confirm L118 as a
      component of the MAb-1G10 binding epitope, and further identify D115 as an
      essential residue. By defining the minimum conformational structure, as well as
      the conformational arrangement of a short peptide sequence recognized by MAb
      1G10, these results introduce the possibility of designing small molecule
      mimetics that may interfere with the function of A33 in vivo. This information
      will also be useful for designing improved assays to evaluate the potency of
      monoclonal and polyclonal products that target A33 or A33-modulated EV
      dissemination.

PMID- 23006743
TI  - Thyroid abnormalities in children and adolescents with McCune-Albright syndrome.
AB  - BACKGROUND: To date, there is no agreement about the frequency or the features of
      thyroid abnormalities in McCune-Albright syndrome (MAS). The aim of our study was
      to detect thyroid abnormalities in a cohort of MAS children and adolescents and
      to give indications for their treatment and follow-up. METHODS: In 36 patients,
      22 females and 14 males, thyroid function and sonographic features of thyroid
      were evaluated every 6-12 months. RESULTS: Three males and 1 female had
      hyperthyroidism: 2 with nodular, 2 with diffuse goiters. They were treated with
      methimazole (0.2-0.5 mg/kg/day) with good clinical and biochemical responses. The
      remaining 32 patients were euthyroid, even if 7 displayed sonographic
      alterations, of whom 5 had nodular goiter with nodules >1 cm, and 2 micronodular
      goiter. Fine-needle aspiration biopsy was performed in 2 patients with nodules >1
      cm, 1 showing hemorrhagic nodule and 1 colloid cystic nodule. CONCLUSIONS:
      Prevalence of thyroid alterations in the studied MAS series was 31%. 64% of 11
      patients with thyroid alterations had nodular goiters, with nodules >1 cm. As the
      onset of thyroid disease ranged from 1 to 20 years, a strict monitoring of
      thyroid function is recommended every 6 months. Satisfactory treatment can be
      obtained and maintained with antithyroid drugs.

PMID- 23006744
TI  - Neglected tropical diseases of Namibia: unsolved mysteries.
AB  - Neglected tropical diseases (NTDs) are diseases most commonly found in settings
      of poverty and are responsible for the morbidity and/or mortality of millions
      each year. As an upper-middle income country, Namibia is not normally considered
      to have many NTDs but published reports indicate the possible presence of over
      30. Because much of the data is buried in historical studies published before
      Independence in 1990, there is a risk of losing valuable information on which to
      build current and future integrated public health strategies. The purpose of this
      review, therefore, is to bring together these significant fragments to identify
      existing knowledge gaps which need to be addressed to build effective control,
      prevention, and even elimination strategies. The review focuses on intestinal
      helminthes, schistosomes/snail 'vectors', viruses (Rift Valley Fever, Crimean
      Congo Hemorrhagic Fever, rabies), protozoa (Leishmania, Toxoplasma, Amoeba,
      Giardia), bacteria (Rickettsia, Ehrlichia, Leptospira, Coxiella, Brucella, and
      Borrelia), fungi (Pneumocystis) and myiasis. Each NTD speaks to the possible need
      for surveillance and the creation of integrated disease risk maps, linking
      prevalence of related NTDs with environmental and ecological factors to assist
      control and prevention efforts. The predominance of zoonotic disease suggests a
      need to integrate veterinary and public health components as the national public
      health surveillance system is established.

PMID- 23006745
TI  - Women who prefer longer penises are more likely to have vaginal orgasms (but not
      clitoral orgasms): implications for an evolutionary theory of vaginal orgasm.
AB  - INTRODUCTION: Research indicates that (i) women's orgasm during penile-vaginal
      intercourse (PVI) is influenced by fitness-related male partner characteristics,
      (ii) penis size is important for many women, and (iii) preference for a longer
      penis is associated with greater vaginal orgasm consistency (triggered by PVI
      without concurrent clitoral masturbation). AIMS: To test the hypothesis that
      vaginal orgasm frequency is associated with women's reporting that a longer than
      average penis is more likely to provoke their PVI orgasm. METHOD: Three hundred
      twenty-three women reported in an online survey their past month frequency of
      various sexual behaviors (including PVI, vaginal orgasm, and clitoral orgasm),
      the effects of a longer than average penis on likelihood of orgasm from PVI, and
      the importance they attributed to PVI and to noncoital sex. MAIN OUTCOME
      MEASURES: Univariate analyses of covariance with dependent variables being
      frequencies of various sexual behaviors and types of orgasm and with independent
      variable being women reporting vs. not reporting that a longer than average penis
      is important for their orgasm from PVI. RESULTS: Likelihood of orgasm with a
      longer penis was related to greater vaginal orgasm frequency but unrelated to
      frequencies of other sexual behaviors, including clitoral orgasm. In binary
      logistic regression, likelihood of orgasm with a longer penis was related to
      greater importance attributed to PVI and lesser importance attributed to
      noncoital sex. CONCLUSIONS: Women who prefer deeper penile-vaginal stimulation
      are more likely to have vaginal orgasm, consistent with vaginal orgasm evolving
      as part of a female mate choice system favoring somewhat larger than average
      penises. Future research could extend the findings by overcoming limitations
      related to more precise measurement of penis length (to the pubis and pressed
      close to the pubic bone) and girth, and large representative samples. Future
      experimental research might assess to what extent different penis sizes influence
      women's satisfaction and likelihood of vaginal orgasm.

PMID- 23006746
TI  - The two-component system CprRS senses cationic peptides and triggers adaptive
      resistance in Pseudomonas aeruginosa independently of ParRS.
AB  - Cationic antimicrobial peptides pass across the outer membrane by interacting
      with negatively charged lipopolysaccharide (LPS), leading to outer membrane
      permeabilization in a process termed self-promoted uptake. Resistance can be
      mediated by the addition of positively charged arabinosamine through the action
      of the arnBCADTEF operon. We recently described a series of two-component
      regulators that lead to the activation of the arn operon after recognizing
      environmental signals, including low-Mg(2+) (PhoPQ, PmrAB) or cationic (ParRS)
      peptides. However, some peptides did not activate the arn operon through ParRS.
      Here, we report the identification of a new two-component system, CprRS, which,
      upon exposure to a wide range of antimicrobial peptides, triggered the expression
      of the LPS modification operon. Thus, mutations in the cprRS operon blocked the
      induction of the arn operon in response to several antimicrobial peptides
      independently of ParRS but did not affect the response to low Mg(2+). Distinct
      patterns of arn induction were identified. Thus, the responses to polymyxins were
      abrogated by either parR or cprR mutations, while responses to other peptides,
      including indolicidin, showed differential dependency on the CprRS and ParRS
      systems in a concentration-dependent manner. It was further demonstrated that,
      following exposure to inducing antimicrobial peptides, cprRS mutants did not
      become adaptively resistant to polymyxins as was observed for wild-type cells.
      Our microarray studies demonstrated that the CprRS system controlled a quite
      modest regulon, indicating that it was quite specific to adaptive peptide
      resistance. These findings provide greater insight into the complex regulation of
      LPS modification in Pseudomonas aeruginosa, which involves the participation of
      at least 4 two-component systems.

PMID- 23006748
TI  - Targeting essential genes in Salmonella enterica serovar typhimurium with
      antisense peptide nucleic acid.
AB  - We investigated the capability of antisense peptide nucleic acids (PNAs)
      conjugated to the (KFF)(3)K cell-penetrating peptide to target possible essential
      genes (ligA, rpoA, rpoD, engA, tsf, and kdtA) in Salmonella enterica serovar
      Typhimurium and inhibit bacterial growth in vitro and in cell culture. All
      targeted PNA-based gene inhibition has shown great potency in gene expression
      inhibition in a sequence-specific and dose-dependent manner at micromolar
      concentrations. Among tested PNAs, the anti-rpoA and -rpoD PNAs showed the
      greatest potency.

PMID- 23006747
TI  - Identification and evaluation of twin-arginine translocase inhibitors.
AB  - The twin-arginine translocase (TAT) in some bacterial pathogens, including
      Pseudomonas aeruginosa, Burkholderia pseudomallei, and Mycobacterium
      tuberculosis, contributes to pathogenesis by translocating extracellular
      virulence determinants across the inner membrane into the periplasm, thereby
      allowing access to the Xcp (type II) secretory system for further export in Gram
      negative organisms, or directly to the outside surface of the cell, as in M.
      tuberculosis. TAT-mediated secretion appreciably contributes to virulence in both
      animal and plant models of bacterial infection. Consequently, TAT function is an
      attractive target for small-molecular-weight compounds that alone or in
      conjunction with extant antimicrobial agents could become novel therapeutics. The
      TAT-transported hemolytic phospholipase C (PlcH) of P. aeruginosa and its
      multiple orthologs produced by the above pathogens can be detected by an accurate
      and reproducible colorimetric assay using a synthetic substrate that detects
      phospholipase C activity. Such an assay could be an effective indicator of TAT
      function. Using carefully constructed recombinant strains to precisely control
      the expression of PlcH, we developed a high-throughput screening (HTS) assay to
      evaluate, in duplicate, >80,000 small-molecular-weight compounds as possible TAT
      inhibitors. Based on additional TAT-related functional assays, purified PlcH
      protein inhibition experiments, and repeat experiments of the initial screening
      assay, 39 compounds were selected from the 122 initial hits. Finally, to evaluate
      candidate inhibitors for TAT specificity, we developed a TAT titration assay that
      determines whether inhibition of TAT-mediated secretion can be overcome by
      increasing the levels of TAT expression. The compounds N-phenyl maleimide and Bay
      11-7082 appear to directly affect TAT function based on this approach.

PMID- 23006749
TI  - Frequency, spectrum, and nonzero fitness costs of resistance to myxopyronin in
      Staphylococcus aureus.
AB  - The antibiotic myxopyronin (Myx) functions by inhibiting bacterial RNA polymerase
      (RNAP). The binding site on RNAP for Myx-the RNAP "switch region SW1/SW2
      subregion"-is different from the binding site on RNAP for the RNAP inhibitor
      currently used in broad-spectrum antibacterial therapy, rifampin (Rif). Here, we
      report the frequency, spectrum, and fitness costs of Myx resistance in
      Staphylococcus aureus. The resistance rate for Myx is 4 * 10(-8) to 7 * 10(-8)
      per generation, which is equal within error to the resistance rate for Rif (3 *
      10(-8) to 10 * 10(-8) per generation). Substitutions conferring Myx resistance
      were obtained in the RNAP beta subunit [six substitutions: V1080(1275)I,
      V1080(1275)L, E1084(1279)K, D1101(1296)E, S1127(1322)L, and S1127(1322)P] and the
      RNAP beta' subunit [five substitutions: K334(345)N, T925(917)K, T925(917)R,
      G1172(1354)C, and G1172(1354)D] (residues numbered as in Staphylococcus aureus
      RNAP and, in parentheses, as in Escherichia coli RNAP). Sites of substitutions
      conferring Myx resistance map to the RNAP switch region SW1/SW2 subregion and do
      not overlap the binding site on RNAP for Rif, and, correspondingly, Myx-resistant
      mutants exhibit no cross-resistance to Rif. All substitutions conferring Myx
      resistance exhibit significant fitness costs (4 to 15% per generation). In
      contrast, at least three substitutions conferring Rif resistance exhibit no
      fitness costs (<=0% per generation). The observation that all Myx-resistant
      mutants have significant fitness costs whereas at least three Rif-resistant
      mutants have no fitness costs, together with the previously established inverse
      correlation between fitness cost and clinical prevalence, suggests that Myx
      resistance is likely to have lower clinical prevalence than Rif resistance.

PMID- 23006750
TI  - Effect of transcriptional activators SoxS, RobA, and RamA on expression of
      multidrug efflux pump AcrAB-TolC in Enterobacter cloacae.
AB  - Control of membrane permeability is a key step in regulating the intracellular
      concentration of antibiotics. Efflux pumps confer innate resistance to a wide
      range of toxic compounds such as antibiotics, dyes, detergents, and disinfectants
      in members of the Enterobacteriaceae. The AcrAB-TolC efflux pump is involved in
      multidrug resistance in Enterobacter cloacae. However, the underlying mechanism
      that regulates the system in this microorganism remains unknown. In Escherichia
      coli, the transcription of acrAB is upregulated under global stress conditions by
      proteins such as MarA, SoxS, and Rob. In the present study, two clinical isolates
      of E. cloacae, EcDC64 (a multidrug-resistant strain overexpressing the AcrAB-TolC
      efflux pump) and Jc194 (a strain with a basal AcrAB-TolC expression level), were
      used to determine whether similar global stress responses operate in E. cloacae
      and also to establish the molecular mechanisms underlying this response. A
      decrease in susceptibility to erythromycin, tetracycline, telithromycin,
      ciprofloxacin, and chloramphenicol was observed in clinical isolate Jc194 and, to
      a lesser extent in EcDC64, in the presence of salicylate, decanoate,
      tetracycline, and paraquat. Increased expression of the acrAB promoter in the
      presence of the above-described conditions was observed by flow cytometry and
      reverse transcription-PCR, by using a reporter fusion protein (green fluorescent
      protein). The expression level of the AcrAB promoter decreased in E. cloacae
      EcDC64 derivates deficient in SoxS, RobA, and RamA. Accordingly, the expression
      level of the AcrAB promoter was higher in E. cloacae Jc194 strains overproducing
      SoxS, RobA, and RamA. Overall, the data showed that SoxS, RobA, and RamA
      regulators were associated with the upregulation of acrAB, thus conferring
      antimicrobial resistance as well as a stress response in E. cloacae. In summary,
      the regulatory proteins SoxS, RobA, and RamA were cloned and sequenced for the
      first time in this species. The involvement of these proteins in conferring
      antimicrobial resistance through upregulation of acrAB was demonstrated in E.
      cloacae.

PMID- 23006752
TI  - Effect of PTX3 and voriconazole combination in a rat model of invasive pulmonary
      aspergillosis.
AB  - This study evaluated the pharmacological activity of PTX3, administered in
      combination with voriconazole, in a rat model of pulmonary aspergillosis. The
      data indicated additive therapeutic activities of these compounds, as
      demonstrated by the amelioration of respiratory function changes, reduction of
      lung fungal burden, and increased survival. Overall, we provide clear evidence
      that the combination of PTX3 with a suboptimal dose of voriconazole might
      represent a therapeutic option under those clinical conditions where the use of
      voriconazole alone is not warranted for efficacy and tolerability reasons.

PMID- 23006751
TI  - A 90-day tenofovir reservoir intravaginal ring for mucosal HIV prophylaxis.
AB  - A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated
      39% protection against HIV infection in women. We designed and evaluated a novel
      reservoir TFV intravaginal ring (IVR) to potentially improve product
      effectiveness by providing a more controlled and sustained vaginal dose to
      maintain cervicovaginal concentrations. Polyurethane tubing of various
      hydrophilicities was filled with a high-density TFV/glycerol/water semisolid
      paste and then end-sealed to create IVRs. In vitro, TFV release increased with
      polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane
      IVRs achieving an approximately 10-mg/day release for 90 days with mechanical
      stiffness similar to that of the commercially available NuvaRing. This design was
      evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and
      safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were
      relatively time independent over the 90-day duration at approximately 10(4) ng/g,
      10(6) ng/g, and 10(1) ng/ml, respectively, near or exceeding the highest observed
      concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations
      were approximately 1,000-fold greater than levels shown to provide significant
      protection in women using the TFV 1% gel. There were no toxicological findings
      following placebo and TFV IVR treatment for 28 or 90 days, although slight to
      moderate increases in inflammatory infiltrates in the vaginal epithelia were
      observed in these animals compared to naive animals. In summary, the controlled
      release of TFV from this reservoir IVR provided elevated sheep vaginal
      concentrations for 90 days to merit its further evaluation as an HIV
      prophylactic.

PMID- 23006753
TI  - Differences in the frequency of 23S rRNA gene mutations in Mycoplasma pneumoniae
      between children and adults with community-acquired pneumonia: clinical impact of
      mutations conferring macrolide resistance.
AB  - We investigated the frequency and clinical significance of macrolide resistance
      in adult and pediatric patients with community-acquired pneumonia from a
      Mycoplasma pneumoniae infection. The frequency of the A2063G mutation in the 23S
      rRNA gene was significantly higher in children than in adults (61.3% [19/31] and
      13.3% [8/60], respectively; P < 0.001). Patients with macrolide-resistant M.
      pneumoniae infections showed a longer duration of fever (P = 0.021) and required
      a longer duration of antibiotic treatment (P = 0.007).

PMID- 23006754
TI  - Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in
      the mouse intestine.
AB  - In vivo bacteriophage targeting of enteroaggregative Escherichia coli (EAEC) was
      assessed using a mouse intestinal model of colonization with the O104:H4 55989Str
      strain and a cocktail of three virulent bacteriophages. The colonization model
      was shown to mimic asymptomatic intestinal carriage found in humans. The addition
      of the cocktail to drinking water for 24 h strongly decreased ileal and weakly
      decreased fecal 55989Str concentrations in a dose-dependent manner. These
      decreases in ileal and fecal bacterial concentrations were only transient, since
      55989Str concentrations returned to their original levels 3 days later. These
      transient decreases were independent of the mouse microbiota, as similar results
      were obtained with axenic mice. We studied the infectivity of each bacteriophage
      in the ileal and fecal environments and found that 55989Str bacteria in the mouse
      ileum were permissive to all three bacteriophages, whereas those in the feces
      were permissive to only one bacteriophage. Our results provide the first
      demonstration that bacterial permissivity to infection with virulent
      bacteriophages is not uniform throughout the gut; this highlights the need for a
      detailed characterization of the interactions between bacteria and bacteriophages
      in vivo for the further development of phage therapy targeting intestinal
      pathogens found in the gut of asymptomatic human carriers.

PMID- 23006756
TI  - Identification of VanN-type vancomycin resistance in an Enterococcus faecium
      isolate from chicken meat in Japan.
AB  - Five VanN-type vancomycin-resistant Enterococcus faecium strains were isolated
      from a sample of domestic chicken meat in Japan. All isolates showed low-level
      resistance to vancomycin (MIC, 12 mg/liter) and had the same pulsed-field gel
      electrophoresis profile. The vancomycin resistance was encoded on a large plasmid
      (160 kbp) and was expressed constitutively. The VanN-type resistance operon was
      identical to the first resistance operon to be reported, with the exception of a
      1-bp deletion in vanT(N) and a 1-bp substitution in vanS(N).

PMID- 23006755
TI  - Noninvasive determination of 2-[18F]-fluoroisonicotinic acid hydrazide
      pharmacokinetics by positron emission tomography in Mycobacterium tuberculosis
      infected mice.
AB  - Tuberculosis (TB) is a global pandemic requiring sustained therapy to facilitate
      curing and to prevent the emergence of drug resistance. There are few adequate
      tools to evaluate drug dynamics within infected tissues in vivo. In this report,
      we evaluated a fluorinated analog of isoniazid (INH), 2-[(18)F]fluoroisonicotinic
      acid hydrazide (2-[(18)F]-INH), as a probe for imaging Mycobacterium tuberculosis
      infected mice by dynamic positron emission tomography (PET). We developed a tail
      vein catheter system to safely deliver drugs to M. tuberculosis aerosol-infected
      mice inside sealed biocontainment devices. Imaging was rapid and noninvasive, and
      it could simultaneously visualize multiple tissues. Dynamic PET imaging
      demonstrated that 2-[(18)F]-INH was extensively distributed and rapidly
      accumulated at the sites of infection, including necrotic pulmonary TB lesions.
      Compared to uninfected animals, M. tuberculosis-infected mice had a significantly
      higher PET signal within the lungs (P < 0.05) despite similar PET activity in the
      liver (P > 0.85), suggesting that 2-[(18)F]-INH accumulated at the site of the
      pulmonary infection. Furthermore, our data indicated that similar to INH, 2
      [(18)F]-INH required specific activation and accumulated within the bacterium.
      Pathogen-specific metabolism makes positron-emitting INH analogs attractive
      candidates for development into imaging probes with the potential to both detect
      bacteria and yield pharmacokinetic data in situ. Since PET imaging is currently
      used clinically, this approach could be translated from preclinical studies to
      use in humans.

PMID- 23006757
TI  - The sequence-activity relationship between metallo-beta-lactamases IMP-1, IMP-6,
      and IMP-25 suggests an evolutionary adaptation to meropenem exposure.
AB  - Metallo-beta-lactamases are important determinants of antibacterial resistance.
      In this study, we investigate the sequence-activity relationship between the
      closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more
      efficient enzyme across the overall spectrum of tested beta-lactam antibacterial
      agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the
      newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation
      distinguishing IMP-25 from IMP-1 and IMP-6 may affect enzyme activity via Asn233.

PMID- 23006758
TI  - Comparison of genospecies and antimicrobial resistance profiles of isolates in
      the Acinetobacter calcoaceticus-Acinetobacter baumannii complex from various
      clinical specimens.
AB  - This study was conducted to compare the prevalences of antimicrobial resistance
      profiles of clinical isolates in the Acinetobacter calcoaceticus-Acinetobacter
      baumannii complex from sterile and nonsterile sites and to further study the
      relationship of antimicrobial resistance profiles and genospecies by amplified
      rRNA gene restriction analysis (ARDRA). A total of 1,381 isolates were tested
      with 12 different antibiotics to show their antimicrobial susceptibility
      profiles. A total of 205 clinical isolates were further analyzed by ARDRA of the
      intergenic spacer (ITS) region of the 16S-23S rRNA gene. It was found that the
      overall percentage of isolates from nonsterile sites (urine, sputum, pus, or
      catheter tip) that were resistant to the 12 antibiotics tested was significantly
      higher than that of isolates from sterile sites (cerebrospinal fluid [CSF],
      ascites fluid, and bloodstream) (46% versus 22%; P < 0.05). After ARDRA, it was
      found that 97% of the 62 isolates resistant to all antibiotics tested were the A.
      baumannii genospecies, which was identified in only 31% of the isolates
      susceptible to all antibiotics tested. More genospecies diversity was identified
      in the isolates susceptible to all antibiotics tested, including genospecies of
      13TU (34%), genotype 3 (29%), and A. calcoaceticus (5%). Furthermore, as 91%
      (10/11) of the isolates from CSF were susceptible to all antibiotics tested, the
      A. calcoaceticus-A. baumannii complex isolates with multidrug resistance could be
      less invasive than the more susceptible isolates. This study also indicated
      current emergence of carbapenem-, fluoroquinolone-, aminoglycoside-, and
      cephalosporin-resistant A. calcoaceticus-A. baumannii complex isolates in Taiwan.

PMID- 23006759
TI  - The Inactivation of intrinsic antibiotic resistance determinants widens the
      mutant selection window for quinolones in Stenotrophomonas maltophilia.
AB  - We have determined that the mutational inactivation of the SmeDEF efflux pump and
      the SmQnr quinolone resistance protein widens the mutant selection windows for
      ofloxacin and ciprofloxacin of Stenotrophomonas maltophilia by reducing their
      MICs. Resistant mutants arising from a strain lacking SmeDEF and SmQnr presented
      levels of susceptibility similar to those of the wild-type strain. This indicates
      that inactivation of intrinsic resistance determinants might increase the chances
      for selecting resistant mutants at low antibiotic concentrations.

PMID- 23006761
TI  - Screening of antifungal azole drugs and agrochemicals with an adapted alamarBlue
      based assay demonstrates antibacterial activity of croconazole against
      Mycobacterium ulcerans.
AB  - An alamarBlue-based growth inhibition assay has been adapted for the
      thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The
      standardized test procedure enables medium-throughput screening of preselected
      compound libraries. Testing of a set of 48 azoles with known antifungal activity
      led to the identification of an imidazole antifungal displaying an inhibitory
      dose (ID) of 9 MUM for M. ulcerans.

PMID- 23006762
TI  - Population-based study of the increased incidence of skin and soft tissue
      infections and associated antimicrobial use.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has
      spread rapidly throughout the world in the last decade. We sought to demonstrate
      the impact of the emergence of CA-MRSA in Western Canada on physician visits,
      incision-and-drainage procedures, and antibiotic prescribing for skin and soft
      tissue infections (SSTI). We used the provincial physician billing system to
      determine the rate of physician visits (per 1,000 population per year) of SSTI
      and incision-and-drainage procedures. A database capturing all outpatient
      prescriptions in the province was anonymously linked to associated physician
      billing codes to quantify prescriptions associated with SSTI. Antibiotic
      prescriptions (overall and class specific) were expressed as their defined daily
      dose (DDD) per 1,000 inhabitants per day. Between 1996 and 2008, the rate of
      visits for all SSTI increased by 15%, and the majority of visits did not include
      an incision-and-drainage procedure. The rate of antibiotic prescribing for SSTI
      increased by 49%. The majority of this increase was attributable to the higher
      rates of use of clindamycin (627%), trimethoprim-sulfamethoxazole (380%),
      cephalosporins (160%), and amoxicillin-clavulanate (627%). Health care
      utilization and antibiotic prescribing rates for SSTI, but not incision-and
      drainage procedures, have increased in association with the CA-MRSA epidemic.
      While much of the increase in antibiotic use reflects an appropriate change to
      trimethoprim-sulfamethoxazole, there is room for education regarding the
      limitations of cephalosporins and clindamycin, given current susceptibility
      profiles.

PMID- 23006763
TI  - Anthropometric and physiological characteristics in young afro-Caribbean
      swimmers. A preliminary study.
AB  - The authors investigated the anthropometric and physiological characteristics of
      young Guadeloupian competitive swimmers in relation to swimming performance and
      compared the abilities of these children with those of the young white swimmers
      reported in the literature. All 2004 competitive swimmers between 10 and 14 y old
      (126 children, 61 boys and 65 girls, 12.0 +/- 1.3 y) from Guadeloupe underwent
      anthropometric measurements and physiological and performance testing. Six boys
      on the French national swimming team are referred to hereafter as the 2011 elite
      subgroup. Anthropometric parameters, a jump-and-reach test, glide, and estimated
      aerobic power (eVO2max) were assessed in terms of swimming-performance analysis
      through a 400-m test. This study demonstrated that the Guadeloupian swimmers had
      more body fat than most age-matched white swimmers but had very poor hydrostatic
      lift; they had higher peak jump height and they swam as well as their white
      counterparts. The variability in 400-m performance between subjects was best
      described by glide, age, and eVO2max. Compared with the group of boys with the
      same age, the 2011 elite subgroup was significantly better for arm span, peak
      jump height, glide, and 400-m and 15-m performances. Further research is needed
      to investigate motor organization and energy cost of swimming in Afro-Caribbean
      swimmers.

PMID- 23006760
TI  - Importance of the genetic diversity within the Mycobacterium tuberculosis complex
      for the development of novel antibiotics and diagnostic tests of drug resistance.
AB  - Despite being genetically monomorphic, the limited genetic diversity within the
      Mycobacterium tuberculosis complex (MTBC) has practical consequences for
      molecular methods for drug susceptibility testing and for the use of current
      antibiotics and those in clinical trials. It renders some representatives of MTBC
      intrinsically resistant against one or multiple antibiotics and affects the
      spectrum and consequences of resistance mutations selected for during treatment.
      Moreover, neutral or silent changes within genes responsible for drug resistance
      can cause false-positive results with hybridization-based assays, which have been
      recently introduced to replace slower phenotypic methods. We discuss the
      consequences of these findings and propose concrete steps to rigorously assess
      the genetic diversity of MTBC to support ongoing clinical trials.

PMID- 23006764
TI  - PathNet: a tool for pathway analysis using topological information.
AB  - BACKGROUND: Identification of canonical pathways through enrichment of
      differentially expressed genes in a given pathway is a widely used method for
      interpreting gene lists generated from high-throughput experimental studies.
      However, most algorithms treat pathways as sets of genes, disregarding any inter-
      and intra-pathway connectivity information, and do not provide insights beyond
      identifying lists of pathways. RESULTS: We developed an algorithm (PathNet) that
      utilizes the connectivity information in canonical pathway descriptions to help
      identify study-relevant pathways and characterize non-obvious dependencies and
      connections among pathways using gene expression data. PathNet considers both the
      differential expression of genes and their pathway neighbors to strengthen the
      evidence that a pathway is implicated in the biological conditions characterizing
      the experiment. As an adjunct to this analysis, PathNet uses the connectivity of
      the differentially expressed genes among all pathways to score pathway contextual
      associations and statistically identify biological relations among pathways. In
      this study, we used PathNet to identify biologically relevant results in two
      Alzheimer's disease microarray datasets, and compared its performance with
      existing methods. Importantly, PathNet identified de-regulation of the ubiquitin
      mediated proteolysis pathway as an important component in Alzheimer's disease
      progression, despite the absence of this pathway in the standard enrichment
      analyses. CONCLUSIONS: PathNet is a novel method for identifying enrichment and
      association between canonical pathways in the context of gene expression data. It
      takes into account topological information present in pathways to reveal
      biological information. PathNet is available as an R workspace image from
      http://www.bhsai.org/downloads/pathnet/.

PMID- 23006765
TI  - Infectious intracranial aneurysm presenting with a series of strokes as a
      complication of pneumococcal meningitis.

PMID- 23006766
TI  - The LO-BaFL method and ALS microarray expression analysis.
AB  - BACKGROUND: Sporadic Amyotrophic Lateral Sclerosis (sALS) is a devastating,
      complex disease of unknown etiology. We studied this disease with microarray
      technology to capture as much biological complexity as possible. The Affymetrix
      focused BaFL pipeline takes into account problems with probes that arise from
      physical and biological properties, so we adapted it to handle the long
      oligonucleotide probes on our arrays (hence LO-BaFL). The revised method was
      tested against a validated array experiment and then used in a meta-analysis of
      peripheral white blood cells from healthy control samples in two experiments. We
      predicted differentially expressed (DE) genes in our sALS data, combining the
      results obtained using the TM4 suite of tools with those from the LO-BaFL method.
      Those predictions were tested using qRT-PCR assays. RESULTS: LO-BaFL filtering
      and DE testing accurately predicted previously validated DE genes in a published
      experiment on coronary artery disease (CAD). Filtering healthy control data from
      the sALS and CAD studies with LO-BaFL resulted in highly correlated expression
      levels across many genes. After bioinformatics analysis, twelve genes from the
      sALS DE gene list were selected for independent testing using qRT-PCR assays.
      High-quality RNA from six healthy Control and six sALS samples yielded the
      predicted differential expression for 7 genes: TARDBP, SKIV2L2, C12orf35, DYNLT1,
      ACTG1, B2M, and ILKAP. Four of the seven have been previously described in sALS
      studies, while ACTG1, B2M and ILKAP appear in the context of this disease for the
      first time. Supplementary material can be accessed at:
      http://webpages.uncc.edu/~cbaciu/LO-BaFL/supplementary_data.html. CONCLUSION: LO
      BaFL predicts DE results that are broadly similar to those of other methods. The
      small healthy control cohort in the sALS study is a reasonable foundation for
      predicting DE genes. Modifying the BaFL pipeline allowed us to remove noise and
      systematic errors, improving the power of this study, which had a small sample
      size. Each bioinformatics approach revealed DE genes not predicted by the other;
      subsequent PCR assays confirmed seven of twelve candidates, a relatively high
      success rate.

PMID- 23006767
TI  - Oxidative stress and activities of caspase-8, -9, and -3 are involved in
      cryopreservation-induced apoptosis in granulosa cells.
AB  - OBJECTIVE: The aim of this study is to determine whether the oxidative stress and
      the activities of caspase-8, -9, and -3 are involved in cryopreservation-induced
      apoptosis in granulosa cells. STUDY DESIGN: Granulosa cells from rats were
      cryopreserved with or without genistein. The level of superoxide dismutase (SOD)
      was measured. Moreover, the expressions of caspase-8, -9, and -3 in both mRNA and
      protein were measured. RESULTS: The SOD level in cryopreserved granulosa cells
      was significantly lower than that in a fresh control group, and the levels of
      caspase-8, -9, and -3 expression in both mRNA and protein in cryopreserved
      granulosa cells were significantly higher than those of fresh control granulosa
      cells. Furthermore, the levels of caspase-8 and -3 expression in both mRNA and
      protein of granulosa cells cryopreserved in presence of genistein were
      significant lower than those of granulosa cells cryopreserved in absence of
      genistein. CONCLUSION: Oxidative stress induced by cryopreservation in granulosa
      cells is involved in the activation of caspase-8 and -3. Cryopreservation-induced
      apoptosis in granulosa cells is mediated, at least in part, by activation of
      caspase-8, -9, and -3 dependent apoptotic pathways.

PMID- 23006768
TI  - A prospective longitudinal cohort study: evolution of GERD symptoms during the
      course of pregnancy.
AB  - BACKGROUND: Symptoms of gastro-esophageal reflux disease (GERD) in pregnancy are
      reported with a prevalence of 30-80%. The aim of this study was to assess the
      prevalence and severity of GERD symptoms during the course of pregnancy.
      Furthermore current practice in medical care for GERD during pregnancy was
      assessed. METHODS: We performed a prospective longitudinal cohort study on 510
      pregnant women (mean age 28.12, SD 5.3). Investigations for reflux symptoms where
      based on the use of validated reflux-disease questionnaire (RDQ). Additional
      information was collected about the therapy. A group of non-pregnant women (mean
      age 24.56, SD 5.7) was included as controls. Frequency and severity of reflux
      symptoms were recorded in each trimester of pregnancy. RESULTS: The prevalence of
      GERD symptoms in pregnant women increased from the first trimester with 26.1 to
      36.1% in the second trimester and to 51.2% in the third trimester of pregnancy.
      The prevalence of GERD symptoms in the control group was 9.3%.Pregnant women
      received medication for their GERD symptoms in 12.8% during the first, 9.1%
      during the second and 15.7% during the third trimester. Medications used >90%
      antacids, 0% PPI. CONCLUSION: GERD symptoms occur more often in pregnant women
      than in non-pregnant and the frequency rises in the course of pregnancy. Medical
      therapy is used in a minority of cases and often with no adequate symptom relief.

PMID- 23006769
TI  - Could the geomagnetic field be an effect modifier for studies of power-frequency
      magnetic fields and childhood leukaemia?
AB  - Epidemiological studies find an association between power-frequency magnetic
      fields and childhood leukaemia. One candidate mechanism for a causal link is
      effects of magnetic fields on biological reactions involving free radicals. This
      mechanism predicts effects from variations in static, as well as alternating,
      magnetic fields, and therefore different consequences at different locations on
      the earth's surface due to variations in geomagnetic field. Testing this directly
      is problematic. Instead, we investigate whether geomagnetic field appears to be
      an effect modifier in studies of alternating magnetic fields. We find some, but
      rather limited and not statistically significant, evidence for this, and discuss
      the implications.

PMID- 23006770
TI  - Animal research ethics in Africa: is Tanzania making progress?
AB  - The significance of animals in research cannot be over-emphasized. The use of
      animals for research and training in research centres, hospitals and schools is
      progressively increasing. Advances in biotechnology to improve animal
      productivity require animal research. Drugs being developed and new interventions
      or therapies being invented for cure and palliation of all sorts of animal
      diseases and conditions need to be tested in animals for their safety and
      efficacy at some stages of their development. Drugs and interventions for human
      use pass through a similar development process and must be tested pre-clinically
      in laboratory animals before clinical trials in humans can be conducted.
      Therefore, animals are important players in research processes which directly and
      indirectly benefit animals and humans. However, questions remain as to whether
      these uses of animals consider the best interests of animals themselves. Various
      research and training institutions in Tanzania have established some guidelines
      on animal use, including establishing animal ethics committees. However, most
      institutions have not established oversight committees. In institutions where
      there may be guidelines and policies, there are no responsible committees or
      units to directly oversee if and how these guidelines and policies are enforced;
      thus, implementation becomes difficult or impossible. This paper endeavours to
      raise some issues associated with the responsible use of animals in research and
      training in Tanzania and highlights suggestions for improvement of deficiencies
      that exist in order to bridge the gap between what ought to be practised and what
      is practised. 

PMID- 23006771
TI  - Organic materials in the wall paintings in Pompei: a case study of Insula del
      Centenario.
AB  - BACKGROUND: The present research concerns the Roman wall paintings preserved at
      Insula del Centenario (IX, 8), the important Pompeian block situated in the Regio
      IX, along Via di Nola. RESULTS: The aims of this research are two: to verify the
      presence of lipidic and proteinaceous material to spread the pigments, and to
      identify organic matter in painting materials owing to previous restoration
      works. The samples collected from the wall paintings of different rooms have been
      investigated by Fourier Transform Infrared Spectroscopy (FT-IR), and Gas
      Chromatography/ Mass Spectrometry (GC/MS). CONCLUSIONS: The analytical results
      show that these Roman wall paintings were realized without the use of lipidic and
      proteinaceous materials, supposedly in fresco technique. Moreover, it was
      detected that wax, egg, and animal glue were used in previous restoration works
      for protective purpose and to restore the wall paintings to their original
      brilliant colours.

PMID- 23006772
TI  - Know your patient: psychological drivers of decision making.
AB  - This is a commentary on "Attitudes of legal guardians of ventilated ICU patients
      toward the process of decision making associated with invasive nonlife-saving
      procedures" by Michael Kuniavsky, Freda DeKeyser Ganz, David M Linton, and Sigal
      Sviri. Kuniavsky and colleagues report that decision-making for the seriously ill
      is difficult for the patients' legal guardians, many of whom would be comfortable
      with doctors making the decisions. This commentary offers that accurate
      predictions about treatment choices may be derived by using assessments that
      characterize the key drivers of individual's decision making, thus relieving some
      of decision makers' burdens. This approach could also usher in an era of
      assessing quality of care for the seriously ill by whether the care matches
      patient goals.

PMID- 23006773
TI  - A systematic approach to the differential diagnosis and management of the
      complications of monochorionic twin pregnancies.
AB  - Monochorionic (MC) twins represent a significant proportion of perinatal
      morbidity and mortality. Overall, 1 of 3 MC twin pregnancies will develop
      complications in relation to the MC placenta and the presence of interfetal
      placental anastomoses. From a clinical standpoint, these complications can be
      grouped into four main types of clinical problems: chronic transfusion, acute
      transfusion, growth discordance, and discordant malformation. Differential
      diagnosis of MC twin complications is still challenging due to frequent overlap
      of their clinical signs and the complex relationships between them. Clinical
      experience demonstrates that most instances of wrong management derive from
      failure to comply with a basic set of rules for diagnosis and management. In this
      review, we propose a simplified approach to the understanding of MC twin
      pregnancy, its potential complications, and the key concepts allowing adequate
      differential diagnosis and targeted management.

PMID- 23006774
TI  - Carotid intima-media thickness provides evidence that ascending aortic aneurysm
      protects against systemic atherosclerosis.
AB  - Previous evaluation of total aortic calcium score suggests that mutations
      promoting ascending aortic aneurysm development may protect against
      atherosclerosis. However, calcium score is a late indicator of atherosclerosis.
      We evaluated carotid intima-media thickness (IMT), an earlier marker, to assess
      the degree of atherosclerosis in ascending aortic aneurysm patients compared to
      controls. Images of right and left common carotid arteries were obtained in 52
      patients with ascending aortic aneurysms and 29 controls using a Sonosite
      MicroMaxx ultrasound. IMT was measured with Sonosite Sonocalc IMT software, a
      computer-based algorithm with manual override. Six IMT measurements were obtained
      for each patient (right and left proximal, mid and distal common carotid artery)
      by a single observer and averaged. A multiple linear regression analysis was
      applied to test for an association between aneurysm and IMT. Patients with
      ascending aortic aneurysms had 0.131-mm lower carotid IMT values than controls (p
      = 0.0002), independent of risk factors for atherosclerosis (age, BMI, gender,
      family history, smoking, dyslipidemia, race, diabetes and hypertension). The
      average IMT was 0.50 +/- 0.13 mm for individuals with aneurysm and 0.60 +/- 0.11
      mm for controls. Age increased the IMT by 0.005 mm per year (p = 0.0003). BMI,
      male gender, positive family history, dyslipidemia, diabetes and hypertension
      also increased the IMT, but did not reach statistical significance. This
      investigation provides further evidence that ascending aortic aneurysm provides
      protection against the development of atherosclerosis, supporting the hypothesis
      that proaneurysmal genetic mutations may also be antiatherogenic.

PMID- 23006775
TI  - beta3GnT2 null mice exhibit defective accessory olfactory bulb innervation.
AB  - Vomeronasal sensory neurons (VSNs) extend axons to the accessory olfactory bulb
      (AOB) where they form synaptic connections that relay pheromone signals to the
      brain. The projections of apical and basal VSNs segregate in the AOB into
      anterior (aAOB) and posterior (pAOB) compartments. Although some aspects of this
      organization exhibit fundamental similarities with the main olfactory system, the
      mechanisms that regulate mammalian vomeronasal targeting are not as well
      understood. In the olfactory epithelium (OE), the glycosyltransferase beta3GnT2
      maintains expression of axon guidance cues required for proper glomerular
      positioning and neuronal survival. We show here that beta3GnT2 also regulates
      guidance and adhesion molecule expression in the vomeronasal system in ways that
      are partially distinct from the OE. In wildtype mice, ephrinA5(+) axons project
      to stereotypic subdomains in both the aAOB and pAOB compartments. This pattern is
      dramatically altered in beta3GnT2(-/-) mice, where ephrinA5 is upregulated
      exclusively on aAOB axons. Despite this, apical and basal VSN projections remain
      strictly segregated in the null AOB, although some V2r1b axons that normally
      project to the pAOB inappropriately innervate the anterior compartment. These
      fibers appear to arise from ectopic expression of V2r1b receptors in a subset of
      apical VSNs. The homotypic adhesion molecules Kirrel2 and OCAM that facilitate
      axon segregation and glomerular compartmentalization in the main olfactory bulb
      are ablated in the beta3GnT2(-/-) aAOB. This loss is accompanied by a two-fold
      increase in the total number of V2r1b glomeruli and a failure to form
      morphologically distinct glomeruli in the anterior compartment. These results
      identify a novel function for beta3GnT2 glycosylation in maintaining expression
      of layer-specific vomeronasal receptors, as well as adhesion molecules required
      for proper AOB glomerular formation.

PMID- 23006776
TI  - Identification of small molecule Hes1 modulators as potential anticancer
      chemotherapeutics.
AB  - Hes1 is a key transcriptional regulator primarily controlled by the Notch
      signaling pathway, and recent studies have demonstrated both an oncogenic and
      tumor suppressor role for Hes1, depending on the cell type. Small molecules that
      activate and inhibit Hes1 activity hold promise as future anticancer
      chemotherapeutics. We have utilized a cell-based dual luciferase assay to
      identify modulators of Hes1 expression in a medium-throughput format. A modest
      screen was performed in HCT-116 colon cancer cell lines, and two small molecules
      were identified and characterized as Hes1 regulators. Compound 3 induced Hes1
      expression and exhibited anticancer effects in pulmonary carcinoid tumor cells, a
      cell type in which the upregulated Notch/Hes1 signaling plays a tumor suppressive
      role. Treatment of HCT-116 cells with compound 12 resulted in Hes1 downregulation
      and antitumor effects.

PMID- 23006777
TI  - Population-genetic analysis of HvABCG31 promoter sequence in wild barley (Hordeum
      vulgare ssp. spontaneum).
AB  - BACKGROUND: The cuticle is an important adaptive structure whose origin played a
      crucial role in the transition of plants from aqueous to terrestrial conditions.
      HvABCG31/Eibi1 is an ABCG transporter gene, involved in cuticle formation that
      was recently identified in wild barley (Hordeum vulgare ssp. spontaneum). To
      study the genetic variation of HvABCG31 in different habitats, its 2 kb promoter
      region was sequenced from 112 wild barley accessions collected from five natural
      populations from southern and northern Israel. The sites included three mesic and
      two xeric habitats, and differed in annual rainfall, soil type, and soil water
      capacity. RESULTS: Phylogenetic analysis of the aligned HvABCG31 promoter
      sequences clustered the majority of accessions (69 out of 71) from the three
      northern mesic populations into one cluster, while all 21 accessions from the
      Dead Sea area, a xeric southern population, and two isolated accessions (one from
      a xeric population at Mitzpe Ramon and one from the xeric 'African Slope' of
      "Evolution Canyon") formed the second cluster. The southern arid populations
      included six haplotypes, but they differed from the consensus sequence at a large
      number of positions, while the northern mesic populations included 15 haplotypes
      that were, on average, more similar to the consensus sequence. Most of the
      haplotypes (20 of 22) were unique to a population. Interestingly, higher genetic
      variation occurred within populations (54.2%) than among populations (45.8%).
      Analysis of the promoter region detected a large number of transcription factor
      binding sites: 121-128 and 121-134 sites in the two southern arid populations,
      and 123-128,125-128, and 123-125 sites in the three northern mesic populations.
      Three types of TFBSs were significantly enriched: those related to GA
      (gibberellin), Dof (DNA binding with one finger), and light. CONCLUSIONS: Drought
      stress and adaptive natural selection may have been important determinants in the
      observed sequence variation of HvABCG31 promoter. Abiotic stresses may be
      involved in the HvABCG31 gene transcription regulations, generating more
      protective cuticles in plants under stresses.

PMID- 23006779
TI  - Enhanced detection of emotional facial expressions in borderline personality
      disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is commonly proposed to be
      characterized by an enhanced sensitivity for emotional stimuli. In the present
      study, we investigated whether BPD patients show a superior detection of
      emotional facial expressions relative to healthy controls. The detection of
      emotional information in the environment represents an important facet of
      emotional sensitivity. SAMPLING AND METHODS: Twenty patients with BPD were
      compared with 25 healthy controls. The participants were presented a rapid,
      continuous stream of neutral and randomly inserted emotional facial expressions
      and were asked to report the presentation of an emotional facial stimulus after
      each trial. Availability of cognitive resources was manipulated via two different
      task demands. RESULTS: The participants with BPD performed significantly better
      in the detection of positive and negative facial expressions compared to the
      healthy controls. False alarm rates did not differ significantly between the two
      groups. CONCLUSIONS: The BPD participants showed an enhanced detection of
      emotional expressions that might be related to the emotional disturbances they
      experience. In particular, we will discuss the role of this superior emotion
      detection (in combination with previously reported deficits in the labeling of
      emotional states) for the understanding of emotional instability in BPD.

PMID- 23006778
TI  - Viral metagenomics demonstrates that domestic pigs are a potential reservoir for
      Ndumu virus.
AB  - BACKGROUND: The rising demand for pork has resulted in a massive expansion of pig
      production in Uganda. This has resulted in increased contact between humans and
      pigs. Pigs can act as reservoirs for emerging infectious diseases. Therefore
      identification of potential zoonotic pathogens is important for public health
      surveillance. In this study, during a routine general surveillance for African
      swine fever, domestic pigs from Uganda were screened for the presence of RNA and
      DNA viruses using a high-throughput pyrosequencing method. FINDINGS: Serum
      samples from 16 domestic pigs were collected from five regions in Uganda and
      pooled accordingly. Genomic DNA and RNA were extracted and sequenced on the 454
      GS-FLX platform. Among the sequences assigned to a taxon, 53% mapped to the
      domestic pig (Sus scrofa). African swine fever virus, Torque teno viruses (TTVs),
      and porcine endogenous retroviruses were identified. Interestingly, two pools (B
      and C) of RNA origin had sequences that showed 98% sequence identity to Ndumu
      virus (NDUV). None of the reads had identity to the class Insecta indicating that
      these sequences were unlikely to result from contamination with mosquito nucleic
      acids. CONCLUSIONS: This is the first report of the domestic pig as a vertebrate
      host for Ndumu virus. NDUV had been previously isolated only from culicine
      mosquitoes. NDUV therefore represents a potential zoonotic pathogen, particularly
      given the increasing risk of human-livestock-mosquito contact.

PMID- 23006780
TI  - Hyperoxia changes the balance of the thioredoxin/peroxiredoxin system in the
      neonatal rat brain.
AB  - Reactive oxygen species (ROS) and intrinsic antioxidant defense systems play an
      important role in both physiological cell signaling processes and many
      pathological states, including neurodegenerative disorders and oxygen-toxicity.
      Here we report that short exposures to non-physiologic oxygen levels change the
      balance of the ROS-dependent thioredoxin/peroxiredoxin system in the developing
      rat brain. The aim of this study was to evaluate the expression of
      peroxiredoxins, thioredoxin 1, sulfiredoxin 1, and DJ-1 on gene and protein level
      under hyperoxic conditions. Six-days old Wistar rats were exposed to 80% oxygen
      for 6-48 h while sex-matched littermates were kept in room-air and served as
      controls. Oxygen-toxicity significantly induced upregulation of peroxiredoxins 1
      and 2, peroxiredoxin sulfonic form, thioredoxin 1, and sulfiredoxin 1 in the
      brains of infant rats. Additionally, hyperoxia reduced the level of DJ-1, a
      hydroperoxide-responsive protein in the developing rat brain. The pathology of
      hyperoxia-mediated injury to the developing brain is still elusive and oxygen
      administration to neonates is often inevitable. These findings may provide
      evidence for the development of targeted therapeutic strategies to enhance the
      antioxidative defense of the immature brain.

PMID- 23006784
TI  - Crush, culotte, T and protrusion: which 2-stent technique for treatment of true
      bifurcation lesions? - insights from in vitro experiments and micro-computed
      tomography.
AB  - BACKGROUND: Percutaneous coronary intervention of complex true bifurcation
      lesions often fails to ensure continuous stent coverage and strut apposition in
      both the side branch and main vessel. Struts left unopposed floating in the lumen
      disturb blood flow and are increasingly recognized as increasing the risk of
      stent thrombosis. METHODS AND RESULTS: In this study, we compared the results of
      different bifurcation treatment strategies: Crush (n=5); Culotte (n=3); T-/T with
      Protrusion (TAP) (n=4) using drug-eluting stents deployed in-vitro in
      representative coronary bifurcation models. After final kissing balloon post
      dilatation, the rate of malapposition within the bifurcation quantified from
      micro-computed tomography scanning was on average 41.5 +/- 8.2% with the Crush
      technique, reduced to respectively 31.4 +/- 5.2% with Culotte and 36.7 +/- 8.0%
      with T-/TAP approach. Overlaying layers of struts in the Crush and Culotte
      techniques lead to a significantly higher rate of strut malapposition in the
      proximal vessel than with the T-/TAP technique (Crush: 39.1 +/- 10.7%, Culotte:
      26.1 +/- 7.7%, TAP: 4.2 +/- 7.2%, P<0.01). Maximal wall-malapposed strut distance
      was also found on average to be higher with the Crush (1.36 +/- 0.4mm) and
      Culotte techniques (1.32 +/- 0.1mm) than with T-/TAP (1.08 +/- 0.1mm, P=0.04).
      CONCLUSIONS: In this model, the Crush technique resulted in a higher risk of
      malapposition than either the Culotte or T-/TAP technique.

PMID- 23006781
TI  - Cause of death in Japanese patients with amyotrophic lateral sclerosis on
      tracheostomy-positive pressure ventilation.

PMID- 23006785
TI  - An investigation into the knowledge and attitudes towards radon testing among
      residents in a high radon area.
AB  - The  aim of this study was to investigate the knowledge and attitudes of
      residents in the Castleisland area to radon. Castleisland in Co. Kerry was
      described as a high radon area following the discovery of a house in the area
      with radon levels 245 times that of the national reference level. Residents in
      this area were then asked to measure their homes for radon in the Castleisland
      radon survey. The uptake of this measurement was 17%. In order to investigate
      this response rate further, a questionnaire was designed and distributed to
      residents in the Castleisland area. This questionnaire measured the testing
      history of the participants, the reasons for testing/not testing, the factors
      important to them when considering having their home tested, radon knowledge and
      finally intentions to measure their home for radon. It was found that the main
      reason people do not test their home for radon is that they believe their home
      does not have a problem. Optimistic bias was thought to play a role here. The
      subjective norm component of the theory of planned behaviour was found to have a
      significant independent contribution in the variation in intentions to measure
      one's home for radon and this in turn could be targeted to increase uptake of
      radon measurement in the future.

PMID- 23006786
TI  - Selective delivery of interleukine-1 receptor antagonist to inflamed joint by
      albumin fusion.
AB  - BACKGROUND: Interleukin-1 receptor antagonist, a cytokine that is highly
      therapeutic to rheumatoid arthritis and several other inflammatory diseases,
      exhibits rapid blood clearance and poor retention time on the target in clinical
      application due to its small size and lack of specificity to target tissue.
      Albumin has been widely employed as macromolecular carrier for drug delivery
      purpose to extend the plasma half-life of therapeutic molecules and has been
      shown to selectively accumulate and to be metabolized in the inflamed joints of
      patients with rheumatoid arthritis. This suggests that genetic fusion of IL-1ra
      to albumin can probably overcome the drawbacks of in vivo application of IL-1ra.
      RESULT: A recombinant protein, engineered by fusing human serum albumin (HSA) to
      the carboxyl terminal of IL-1ra, was produced in Pichia pastoris and purified to
      homogeneity. The fusion protein retained the antagonist activity of IL-1ra and
      had a plasma half-life of approximately 30-fold more than that of IL-1ra in
      healthy mice. In vivo bio-distribution studies demonstrated that the fusion
      protein selectively accumulated in arthritic paws for a long period of time in
      mice with collagen-induced arthritis, showing low uptake rates in normal organs
      such as liver, kidney, spleen and lung in contrast to IL-1ra alone. Moreover,
      this fusion protein was able to significantly improve the therapeutic efficacy of
      IL-1ra in collagen-induced arthritis mouse model. CONCLUSIONS: The fusion protein
      described here, able to selectively deliver IL-1ra to inflamed tissue, could
      yield important contributions for the therapy of rheumatoid arthritis and other
      inflammatory diseases.

PMID- 23006787
TI  - Immediate effect of kinesio taping on muscle response in young elite soccer
      players.
AB  - CONTEXT: Kinesio taping (KT) is a new taping technique increasingly used in
      sports medicine to improve muscle performance; however, its real effect is not
      entirely known. OBJECTIVE: To assess the immediate effects of KT on muscle
      performance in young healthy elite soccer players. DESIGN: Crossover study.
      SETTING: University laboratory. PARTICIPANTS: Eighteen young elite soccer players
      voluntarily participated in the study (mean +/- SEM: age 18.20 +/- 2.45 y, height
      1.76 +/- 3.56 m, body mass 65.25 +/- 3.76 kg, body-mass index 20.12 +/- 1.25
      kg/m2). INTERVENTIONS: Each subject completed 2 different protocols, with and
      without KT. Interventions were performed in a random order, with a washout period
      between conditions of 1 wk. MAIN OUTCOME MEASURES: Outcome measures included
      tensiomyographic response in the vastus lateralis and vastus medialis, power
      output with 30 and 50 kg, countermovement jump, and 10-m sprint. RESULTS: Data
      showed no significant differences for any of the outcomes analyzed between
      interventions. CONCLUSIONS: KT does not produce a short-term improvement in
      muscle performance in young elite soccer players.

PMID- 23006788
TI  - Microbial diversity of Loki's Castle black smokers at the Arctic Mid-Ocean Ridge.
AB  - Hydrothermal vent systems harbor rich microbial communities ranging from aerobic
      mesophiles to anaerobic hyperthermophiles. Among these, members of the archaeal
      domain are prevalent in microbial communities in the most extreme environments,
      partly because of their temperature-resistant and robust membrane lipids. In this
      study, we use geochemical and molecular microbiological methods to investigate
      the microbial diversity in black smoker chimneys from the newly discovered Loki's
      Castle hydrothermal vent field on the Arctic Mid-Ocean Ridge (AMOR) with vent
      fluid temperatures of 310-320  degrees C and pH of 5.5. Archaeal glycerol dialkyl
      glycerol tetraether lipids (GDGTs) and H-shaped GDGTs with 0-4 cyclopentane
      moieties were dominant in all sulfide samples and are most likely derived from
      both (hyper)thermophilic Euryarchaeota and Crenarchaeota. Crenarchaeol has been
      detected in low abundances in samples derived from the chimney exterior
      indicating the presence of Thaumarchaeota at lower ambient temperatures.
      Aquificales and members of the Epsilonproteobacteria were the dominant bacterial
      groups detected. Our observations based on the analysis of 16S rRNA genes and
      biomarker lipid analysis provide insight into microbial communities thriving
      within the porous sulfide structures of active and inactive deep-sea hydrothermal
      vents. Microbial cycling of sulfur, hydrogen, and methane by archaea in the
      chimney interior and bacteria in the chimney exterior may be the prevailing
      biogeochemical processes in this system.

PMID- 23006789
TI  - Association between oral 5-ASA adherence and health care utilization and costs
      among patients with active ulcerative colitis.
AB  - BACKGROUND: Observational cohort study to assess the association between
      adherence to oral 5-aminosalicylates (5-ASAs) and all-cause costs and health care
      utilization among patients with active ulcerative colitis (UC) in the United
      States. METHODS: Retrospective analysis of insurance claims from June 1997 to
      August 2006 in the LifeLink Database. Patient criteria: aged 18 or older with one
      or more claim(s) between June 1997 and August 2005 for a UC diagnosis and at
      least one oral 5-ASA prescription on or after the first observed UC diagnosis;
      continuous enrollment for at least 6 months prior to and 12 months following 5
      ASA initiation (index date). As a proxy for active disease, patients needed to
      have at least two UC-specific non-pharmacy claims, at least 30 days of 5-ASA
      treatment and at least one corticosteroid prescription within the 12-month post
      index period. Cumulative exposure to oral 5-ASAs over the 12-month period was
      calculated using the medication possession ratio (MPR). Patients with an MPR of
      at least 0.80 were classified as adherent. All-cause medical and pharmacy
      resource utilization and costs were computed over the 12-month post-index period
      and compared between adherent and nonadherent patients. RESULTS: 1,693 UC
      patients met study inclusion criteria: 72% were nonadherent to 5-ASA treatment
      (n=1,217) and 28% were adherent (n=476) in the 12-month study period. Compared
      with nonadherent patients, adherent patients had 31% fewer hospitalizations
      (P=0.0025) and 34% fewer emergency department admissions (P=0.0016). Adherent
      patients had 25% more pharmacy prescriptions overall (P <0.0001) and 71% more UC
      related pharmacy prescriptions (P <0.0001) than did nonadherent patients. Total
      all-cause health care utilization was 1.13 times higher for adherent patients
      than for nonadherent patients (P=0.0002). After adjusting for covariates, total
      all-cause costs were 29% higher for nonadherent patients than for adherent
      patients (mean [95% confidence interval]: $13,465 [$13,094, $13,835] vs $17,339
      [$17,033, $17,645]). CONCLUSIONS: Approximately three-quarters of patients with
      active UC were not adherent with their prescribed doses of oral 5-ASA.
      Nonadherence was associated with higher total all-cause costs. The key driver of
      decreased costs among adherent patients was inpatient hospitalizations, which
      more than offset these patients' expected higher pharmacy costs.

PMID- 23006790
TI  - Foot-strike pattern and performance in a marathon.
AB  - PURPOSE: To determine prevalence of heel strike in a midsize city marathon, if
      there is an association between foot-strike classification and race performance,
      and if there is an association between foot-strike classification and gender.
      METHODS: Foot-strike classification (forefoot, midfoot, heel, or split strike),
      gender, and rank (position in race) were recorded at the 8.1-km mark for 2112
      runners at the 2011 Milwaukee Lakefront Marathon. RESULTS: 1991 runners were
      classified by foot-strike pattern, revealing a heel-strike prevalence of 93.67%
      (n = 1865). A significant difference between foot-strike classification and
      performance was found using a Kruskal-Wallis test (P < .0001), with more elite
      performers being less likely to heel strike. No significant difference between
      foot-strike classification and gender was found using a Fisher exact test. In
      addition, subgroup analysis of the 126 non-heel strikers found no significant
      difference between shoe wear and performance using a Kruskal-Wallis test.
      CONCLUSIONS: The high prevalence of heel striking observed in this study reflects
      the foot-strike pattern of most mid-distance to long-distance runners and, more
      important, may predict their injury profile based on the biomechanics of a heel
      strike running pattern. This knowledge can help clinicians appropriately
      diagnose, manage, and train modifications of injured runners.

PMID- 23006791
TI  - Gastric lipoma presenting as a giant bulging mass in an oligosymptomatic patient:
      a case report.
AB  - INTRODUCTION: Lipomas of the gastrointestinal tract are a rare condition. Only 5%
      are of gastric origin, and this corresponds to 2% to 3% of all benign tumors of
      the stomach and less than 1% of all gastric neoplasms. It is our purpose to
      report an unusual presentation of a giant gastric lipoma in an oligosymptomatic
      patient and highlight the importance of discussing differential diagnosis in this
      situation. A review of the literature has shown that this is one of the largest
      gastric lipomas described. CASE PRESENTATION: We describe a rare case of a benign
      gastric tumor with uncommon features in a 63-year-old Caucasian woman. She was
      admitted with abdominal discomfort, nausea, and upper abdominal fullness after
      eating. The lesion was suspicious of malignancy because of its dimension and
      central contrast enhancement on computed tomography. Conventional upper digestive
      endoscopy revealed a large bulging mass in the gastric posterior wall and three
      ulcerated areas. In this procedure, a technical limitation due to the location of
      the mass in the submucosa prevented an adequate biopsy from being obtained. The
      fragments obtained from the ulcers revealed nothing but necrotic mucosa. Our
      patient underwent a subtotal gastrectomy and D1 lymphadenectomy with a Roux-en-Y
      reconstruction. Macroscopic findings revealed a 12 * 8 * 6cm mass with a volume
      of 576cm3, and the histological pattern demonstrated well-differentiated mature
      adipose tissue surrounded by a fibrous capsule, confirming the diagnosis of
      gastric submucosal lipoma. CONCLUSIONS: Gastric lipoma is a rare benign disease
      that eventually simulates a malignant tumor.

PMID- 23006792
TI  - CST6 promoter methylation in circulating cell-free DNA of breast cancer patients.
AB  - OBJECTIVES: We have recently shown that detection of CST6 promoter methylation in
      primary breast tumors can provide important prognostic information in patients
      with operable breast cancer and that CST6 promoter is also methylated in
      Circulating Tumor Cells (CTC). In this study we evaluated the presence of CST6
      promoter methylation in cell-free DNA (cfDNA) circulating in plasma of breast
      cancer patients. DESIGN AND METHODS: Our study material consisted of: a) a pilot
      testing group of 27 patients with stage I-III operable breast cancer, 46 patients
      with verified metastasis and 37 healthy donors and b) an independent cohort of
      123 consecutive stage I-III operable breast cancer patients. Methylated and
      unmethylated CST6 promoter sequences were detected by using methylation-specific
      PCR (MSP). CST6 immunohistochemical detection was performed in 20 corresponding
      primary tumor tissues. RESULTS: In the pilot testing group, CST6 promoter was
      methylated in 8/27 (29.6%) operable breast cancer patients, in 6/46 (13.0%)
      patients with verified metastasis but none of 37 healthy individuals (0%). In the
      independent cohort, 49/123 (39.8%) operable breast cancer patients were found
      positive. During the follow up period, 25/123 (20.3%) patients relapsed and 9/123
      (7.3%) died. CST6 was methylated in cfDNA of 13/25 (52%) patients that relapsed
      and in 3/9 (33.3%) patients that died. CONCLUSIONS: CST6 promoter is highly
      methylated in cfDNA of breast cancer patients, but not in healthy individuals.
      CST6 promoter methylation in cfDNA, should be prospectively validated as a novel
      plasma tumor biomarker for breast cancer in a large cohort of breast cancer
      patients.

PMID- 23006793
TI  - Foxp3(+) regulatory T cells are increased in the early stages of halo nevi:
      clinicopathological features of 30 halo nevi.
AB  - BACKGROUND: There have been few clinical studies of the role of regulatory T
      cells (Tregs) in halo formation of halo nevus. OBJECTIVE: To evaluate the
      clinicopathologic features and the presence of Tregs in halo nevi. METHODS: We
      analyzed 30 halo nevi and performed immunohistochemical analysis using antibodies
      against CD4, CD8, CD25 and Foxp3. We also performed double immunohistochemical
      staining for Foxp3 and CD25. RESULTS: We found significant increases in Foxp3(+)
      Tregs, and the shorter the halo nevus duration, the more Foxp3(+) Tregs were
      detected. Also, the ratio of Foxp3 to CD8 T cells was increased in early stages
      of halo nevi. Double immunohistochemical staining suggested that the Tregs in the
      halo nevi were CD25(+)Foxp3(+) T cells. CONCLUSIONS: Foxp3(+) Tregs were greatly
      increased in the halo nevi. The shorter the halo nevi duration, the more Foxp3(+)
      Tregs were involved in the earlier developmental stages of halo nevi.

PMID- 23006794
TI  - Impact of national income and inequality on sugar and caries relationship.
AB  - OBJECTIVE: The aim of this study was to examine the impact that national income
      and income inequality in high and low income countries have on the relationship
      between dental caries and sugar consumption. METHODS: An ecological study design
      was used in this study of 73 countries. The mean decayed, missing, or filled
      permanent teeth (DMFT) for 12-year-old children were obtained from the WHO Oral
      Health Country/Area Profile Programme. United Nations Food and Agricultural
      Organization data were used for per capita sugar consumption. Gross national
      incomes per capita based on purchasing power parity and the Gini coefficient were
      obtained from World Bank data. Bivariate and multivariate linear regression
      analysis was performed to estimate the associations between mean DMFT and per
      capita sugar consumption in different income and income inequality countries.
      RESULTS: Bivariate and multivariate regression analysis showed that countries
      with a high national income and low income inequality have a strong negative
      association between sugar consumption and caries (B = -2.80, R2 = 0.17), whereas
      countries with a low income and high income inequality have a strong positive
      relationship between DMFT and per capita sugar consumption (B = -0.89, R2 =
      0.20). CONCLUSION: The relationship between per capita consumption of sugar and
      dental caries is modified by the absolute level of income of the country, but not
      by the level of income inequality within a country.

PMID- 23006795
TI  - Temporal variation and lack of host specificity among bacterial endosymbionts of
      Osedax bone worms (Polychaeta: Siboglinidae).
AB  - BACKGROUND: Osedax worms use a proliferative root system to extract nutrients
      from the bones of sunken vertebrate carcasses. The roots contain bacterial
      endosymbionts that contribute to the nutrition of these mouthless and gutless
      worms. The worms acquire these essential endosymbionts locally from the
      environment in which their larvae settle. Here we report on the temporal dynamics
      of endosymbiont diversity hosted by nine Osedax species sampled during a three
      year investigation of an experimental whale fall at 1820-m depth in the Monterey
      Bay, California. The host species were identified by their unique mitochondrial
      COI haplotypes. The endosymbionts were identified by ribotyping with PCR primers
      specifically designed to target Oceanospirillales. RESULTS: Thirty-two
      endosymbiont ribotypes associated with these worms clustered into two distinct
      bacterial ribospecies that together comprise a monophyletic group, mostly
      restricted to deep waters (>1000 m). Statistical analyses confirmed significant
      changes in the relative abundances of host species and the two dominant
      endosymbiont ribospecies during the three-year sampling period. Bone type (whale
      vs. cow) also had a significant effect on host species, but not on the two
      dominant symbiont ribospecies. No statistically significant association existed
      between the host species and endosymbiont ribospecies. CONCLUSIONS: Standard PCR
      and direct sequencing proved to be an efficient method for ribotyping the
      numerically dominant endosymbiont strains infecting a large sample of host
      individuals; however, this method did not adequately represent the frequency of
      mixed infections, which appears to be the rule rather than an exception for
      Osedax individuals. Through cloning and the use of experimental dilution series,
      we determined that minority ribotypes constituting less than 30% of a mixture
      would not likely be detected, leading to underestimates of the frequency of
      multiple infections in host individuals.

PMID- 23006796
TI  - Chemotherapy drugs form ion pores in membranes due to physical interactions with
      lipids.
AB  - We demonstrate the effects on membrane of the tubulin-binding chemotherapy drugs:
      thiocolchicoside and taxol. Electrophysiology recordings across lipid membranes
      in aqueous phases containing drugs were used to investigate the drug effects on
      membrane conductance. Molecular dynamics simulation of the chemotherapy drug
      lipid complexes was used to elucidate the mechanism at an atomistic level. Both
      drugs are observed to induce stable ion-flowing pores across membranes. Discrete
      pore current-time plots exhibit triangular conductance events in contrast to
      rectangular ones found for ion channels. Molecular dynamics simulations indicate
      that drugs and lipids experience electrostatic and van der Waals interactions for
      short periods of time when found within each other's proximity. The energies from
      these two interactions are found to be similar to the energies derived
      theoretically using the screened Coulomb and the van der Waals interactions
      between peptides and lipids due to mainly their charge properties while forming
      peptide-induced ion channels in lipid bilayers. Experimental and in silico
      studies together suggest that the chemotherapy drugs induce ion pores inside
      lipid membranes due to drug-lipid physical interactions. The findings reveal
      cytotoxic effects of drugs on the cell membrane, which may aid in novel drug
      development for treatment of cancer and other diseases.

PMID- 23006797
TI  - Polyphosphate multi-tasks.

PMID- 23006798
TI  - Quality of online health information about oral contraceptives from Hebrew
      language websites.
AB  - BACKGROUND: The Internet is a frequently used source of health information.
      Adolescents in particular seem to be receptive to online health information (OHI)
      and often incorporate such information in their decision-making processes. Yet,
      OHI is often incomplete, inaccurate, or unreliable. This study assessed the
      quality of Hebrew online (non-user-generated) content on oral contraceptives
      (OC), with regard to accuracy/completeness, credibility,  and usability. METHODS:
      Twenty-nine websites in Hebrew, including those of the four Israeli HMOs, were
      identified and evaluated. The websites were categorized as: HMO, health portal,
      contraception-specific, promotional-commercial, and life style and women's
      health. A set of established content parameters was selected by a family planning
      expert to assess accuracy/completeness. The Health on the Net Foundation Code of
      Conduct (HONcode) principles were used to assess the websites' reliability.
      Usability was assessed by applying items selected from the Minervation Validation
      and the University of Michigan's 'Website Evaluation checklist' scale. Mean
      scores, standard deviations (SD), and ranges were calculated for all websites and
      for category-specific websites. Correlation between dimensions and Inter-rater
      reliability were also examined. RESULTS: The mean score for accuracy/completeness
      was 50.9% for all websites (SD=30.1%, range 8-100%). Many websites failed to
      provide complete information, or provided inaccurate information regarding what
      to do when a pill is missed and when to use back-up methods. The average
      credibility score for all websites was 70.6% (SD=15.1, range=38=98%). The
      credibility parameters that were most commonly absent were funding source,
      authoring, date of content creation and last modification, explicit reference to
      evidence-based information, and references and citations. The average usability
      score for all websites was 94.5% (SD=6.9%, range 79-100%). A weak correlation was
      found between the three quality parameters assessed. CONCLUSIONS: Wide variation
      was noted in the quality of Hebrew-language OC websites. HMOs' websites scored
      highest on credibility and usability, and contraceptive-specific websites
      exhibited the greatest accuracy/completeness. The findings highlight the need to
      establish quality guidelines for health website content, train health care
      providers in assisting their patients to seek high quality OHI, and strengthen e
      health literacy skills among online-information seekers, including perhaps health
      professionals.

PMID- 23006799
TI  - Mechanism-based treatment of pain.

PMID- 23006800
TI  - Copper, zinc, and Cu/Zn ratio in transitional cell carcinoma of the bladder.
AB  - INTRODUCTION: Many epidemiological and experimental studies report a strong role
      of chemical carcinogens in the etiology of bladder cancer. However, involvement
      of trace elements in the tumorigenesis of transitional cell carcinoma of the
      bladder has been poorly investigated. The aim of this study was to examine the
      relationship between zinc, copper and bladder cancer. MATERIALS AND METHODS: Zinc
      and copper concentration and Cu/Zn ratio in two 36-sample series of bladder
      cancer tissue and sera from patients with this neoplasm were matched with those
      of the control group. The amount of trace elements in every tissue sample was
      determined using atomic absorption spectrometry. This was correlated with tumor
      stage. RESULTS: While the copper concentrations reached statistically higher
      values in the bladder cancer tissue, the zinc levels in the sera and bladder
      tissue of the patients with this carcinoma were substantially lower as compared
      to those of the control group. The serum Cu/Zn ratio was significantly higher in
      the bladder cancer group and this increase was greater in the patients with
      muscle-invasive neoplasm. CONCLUSIONS: The results obtained suggest a
      relationship between trace elements and the bladder cancer.

PMID- 23006801
TI  - The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic
      widespread pain susceptibility.
AB  - BACKGROUND: Mutations in SCN9A, encoding the alpha subunit of the voltage-gated
      sodium channel (Nav1.7), have caused severe pain disorders and congenital
      insensitivity to pain. The aim of this study was to validate the previously
      reported association between a common non-synonymous polymorphism (R1150W,
      rs6746030) in SCN9A and chronic widespread pain (CWP), in independent population
      based cohorts. FINDINGS: Genotype data for rs6746030 was available in four
      population-based cohorts (EPIFUND, the European Male Ageing Study (EMAS), the
      Framingham study and the Dyne Steel DNA Bank of Ageing and Cognition). Pain was
      assessed using body manikins and CWP was scored using American College of
      Rheumatology (ACR) criteria in all cohorts, except the Framingham study which
      assessed widespread pain (WP) using ACR criteria on a joint pain homunculus.
      Controls were subjects who reported no pain. Logistic regression (additive
      genetic model) was used to test for association between rs6746030 and CWP
      compared to controls, adjusting for study centre in EMAS. Generalised estimating
      equation regression was used to test for association between rs6746030 and WP,
      whilst accounting for relatedness between subjects in the Framingham
      study.Genotype data for rs6746030 was available for 1071 CWP cases and 3212
      controls. There was no significant association between CWP and rs6476030 in
      individual cohorts or when combined in a fixed-effects meta-analysis (Odds Ratio
      = 0.96 (95% confidence interval 0.82, 1.11) p = 0.567). CONCLUSIONS: In contrast
      to a previous study, no association between a non-synonymous polymorphism in
      SCN9A and CWP was observed in multiple population-based cohorts.

PMID- 23006802
TI  - Electronic monitoring of symptoms and syndromes associated with cancer: methods
      of a randomized controlled trial SAKK 95/06 E-MOSAIC.
AB  - BACKGROUND: In patients with advanced, incurable cancer, anticancer treatment
      may be used to alleviate cancer-related symptoms, but monitoring of them in daily
      practice is rarely done. We aim to test the effectiveness of a real-time symptom
      and syndrome assessment using the E-MOSAIC software installed in handheld
      computer generating a longitudinal monitoring sheet (LoMoS) provided to the
      oncologists in a phase III setting. METHODS: In this prospective multicentre
      cluster randomized phase-III trial patients with any incurable solid tumor and
      having defined cancer related symptoms, who receive new outpatient chemotherapy
      in palliative intention (expected tumor-size response rate <=20%) are eligible.
      Immediately before the weekly visit to oncologists, all patients complete with
      nurse assistance the E-MOSAIC Assessment: Edmonton Symptom Assessment Scale, <=3
      additional symptoms, estimated nutritional intake, body weight, Karnofsky and
      medications for pain and cachexia. Experienced oncologists will be randomized to
      receive the LoMoS or not. To minimize contamination, LoMoS are removed from the
      medical charts after visits. Primary endpoint is the difference in global quality
      of life (items 29 & 30 of EORTC-QlQ-C30) between baseline and last study visit at
      week 6, with a 10 point between-arm difference considered to be clinically
      relevant. 20 clusters (=oncologists) per treatment arm with 4-8 patients each are
      aimed for to achieve a significance level of 5% and a power of 80% in a mixed
      model approach. Selected co- variables are included in the model for adjustment.
      Secondary endpoints include patient-perceived patient-physician communication
      symptom burden over time, and oncologists' symptom management performance
      (predefined thresholds of symptoms compared to oncologists' pharmacological,
      diagnostic or counselling actions [structured chart review]). DISCUSSION: This
      trial will contribute to the research question, whether structured, longitudinal
      monitoring of patients' multidimensional symptoms, indicators for symptom
      management, and clinical benefit outcomes can influence patients' quality of life
      and symptom distress, in a setting of routine oncology practice. TRIAL
      REGISTRATION: Current Controlled Trials NCT00477919.

PMID- 23006803
TI  - Removing motion and physiological artifacts from intrinsic BOLD fluctuations
      using short echo data.
AB  - Differing noise variance across study populations has been shown to cause
      artifactual group differences in functional connectivity measures. In this study,
      we investigate the use of short echo time functional MRI data to correct for
      these noise sources in blood oxygenation level dependent (BOLD)-weighted time
      series. A dual-echo sequence was used to simultaneously acquire data at both a
      short (TE=3.3 ms) and a BOLD-weighted (TE=35 ms) echo time. This approach is
      effectively "free," using dead-time in the pulse sequence to collect an
      additional echo without affecting overall scan time or temporal resolution. The
      proposed correction method uses voxelwise regression of the short TE data from
      the BOLD-weighted data to remove noise variance. In addition to a typical resting
      state scan, non-compliant behavior associated with patient groups was simulated
      via increased head motion or physiological fluctuations in 10 subjects. Short TE
      data showed significant correlations with the traditional motion-related and
      physiological noise regressors used in current connectivity analyses. Following
      traditional preprocessing, the extent of significant additional variance
      explained by the short TE data regressors was significantly correlated with the
      average head motion across the scan in the resting data (r(2)=0.93, p<0.0001).
      The reduction in data variance following the inclusion of short TE regressors was
      also correlated with scan head motion (r(2)=0.48, p=0.027). Task-related data
      were used to demonstrate the effects of the short TE correction on BOLD
      activation time series with known temporal structure; the size and strength of
      the activation were significantly decreased, but it is not clear whether this
      reflects BOLD contamination in the short TE data or correlated changes in blood
      volume. Finally, functional connectivity maps of the default mode network were
      constructed using a seed correlation approach. The effects of short TE correction
      and low-pass filtering on the resulting correlations maps were compared. Results
      suggest that short TE correction more accurately differentiates artifactual
      correlations from the correlations of interest in conditions of amplified noise.

PMID- 23006804
TI  - The 'where' and the 'when' of the BOLD response to pain in the insular cortex.
      Discussion on amplitudes and latencies.
AB  - The operculo-insular cortex has been recently pointed out to be the main area of
      the pain matrix to be involved in the integration of pain intensity. This fMRI
      study specified the pattern of response to laser stimuli by focusing on this
      cortical area, by optimizing the temporal sampling and by investigating pain
      related differences in the amplitudes and latencies of the BOLD responses.
      Canonical and temporal derivative hemodynamic response function (HRF) and finite
      impulse response (FIR) modeling provided consistent results. Amplitude of BOLD
      response discriminated painful from non-painful conditions in posterior and mid
      insular cortices, bilaterally. Pain conditions were characterized by a shortened
      latency (as compared to non-painful conditions) in the anterior insula. In the
      functional organization of the insula, these results suggest a double
      dissociation that can be summarized as the 'where' and the 'when' of the BOLD
      response to pain. These results suggest that differences in the amplitude of the
      BOLD activity in the posterior and in the mid-insular cortices as well as
      shortened latency of the response in the anterior insula deal with discriminative
      processes related to painful conditions.

PMID- 23006805
TI  - Subject position affects EEG magnitudes.
AB  - EEG (electroencephalography) has been used for decades in thousands of research
      studies and is today a routine clinical tool despite the small magnitude of
      measured scalp potentials. It is widely accepted that the currents originating in
      the brain are strongly influenced by the high resistivity of skull bone, but it
      is less well known that the thin layer of CSF (cerebrospinal fluid) has perhaps
      an even more important effect on EEG scalp magnitude by spatially blurring the
      signals. Here it is shown that brain shift and the resulting small changes in CSF
      layer thickness, induced by changing the subject's position, have a significant
      effect on EEG signal magnitudes in several standard visual paradigms. For
      spatially incoherent high-frequency activity the effect produced by switching
      from prone to supine can be dramatic, increasing occipital signal power by
      several times for some subjects (on average 80%). MRI measurements showed that
      the occipital CSF layer between the brain and skull decreases by approximately
      30% in thickness when a subject moves from prone to supine position. A multiple
      dipole model demonstrated that this can indeed lead to occipital EEG signal power
      increases in the same direction and order of magnitude as those observed here.
      These results suggest that future EEG studies should control for subjects'
      posture, and that some studies may consider placing their subjects into the most
      favorable position for the experiment. These findings also imply that special
      consideration should be given to EEG measurements from subjects with brain
      atrophy due to normal aging or neurodegenerative diseases, since the resulting
      increase in CSF layer thickness could profoundly decrease scalp potential
      measurements.

PMID- 23006806
TI  - A critical assessment of connectivity measures for EEG data: a simulation study.
AB  - Information flow between brain areas is difficult to estimate from EEG
      measurements due to the presence of noise as well as due to volume conduction. We
      here test the ability of popular measures of effective connectivity to detect an
      underlying neuronal interaction from simulated EEG data, as well as the ability
      of commonly used inverse source reconstruction techniques to improve the
      connectivity estimation. We find that volume conduction severely limits the
      neurophysiological interpretability of sensor-space connectivity analyses.
      Moreover, it may generally lead to conflicting results depending on the
      connectivity measure and statistical testing approach used. In particular, we
      note that the application of Granger-causal (GC) measures combined with standard
      significance testing leads to the detection of spurious connectivity regardless
      of whether the analysis is performed on sensor-space data or on sources estimated
      using three different established inverse methods. This empirical result follows
      from the definition of GC. The phase-slope index (PSI) does not suffer from this
      theoretical limitation and therefore performs well on our simulated data. We
      develop a theoretical framework to characterize artifacts of volume conduction,
      which may still be present even in reconstructed source time series as zero-lag
      correlations, and to distinguish their time-delayed brain interaction. Based on
      this theory we derive a procedure which suppresses the influence of volume
      conduction, but preserves effects related to time-lagged brain interaction in
      connectivity estimates. This is achieved by using time-reversed data as
      surrogates for statistical testing. We demonstrate that this robustification
      makes Granger-causal connectivity measures applicable to EEG data, achieving
      similar results as PSI. Integrating the insights of our study, we provide a
      guidance for measuring brain interaction from EEG data. Software for generating
      benchmark data is made available.

PMID- 23006807
TI  - Assessment of Helicobacter pylori eradication in patients on NSAID treatment.
AB  - BACKGROUND: In this post-hoc analysis of a randomized, double blind, placebo
      controlled trial, we measured the sensitivity and specificity of Helicobacter
      pylori IgG-antibody titer changes, hematoxylin and eosin (H&E) stains,
      immunohistochemical (IHC) stains and culture results in NSAID using patients,
      following H. pylori eradication therapy or placebo. METHODS: 347 NSAID using
      patients who were H. pylori positive on serological testing for H. pylori IgG
      antibodies were randomized for H. pylori eradication therapy or placebo. Three
      months after randomization, gastric mucosal biopsies were taken for H. pylori
      culture and histological examination. At 3 and 12 months, blood samples were
      taken for repeated serological testing. The gold standard for H. pylori infection
      was based on a positive culture or both a positive histological examination and a
      positive serological test. Sensitivity, specificity and receiver operating curves
      (ROC) were calculated. RESULTS: H. pylori eradication therapy was successful in
      91% of patients. Culture provided an overall sensitivity of 82%, and 73% after
      eradication, with a specificity of 100%. Histological examination with either H&E
      or IHC stains provided sensitivities and specificities between 93% and 100%.
      Adding IHC to H&E stains did not improve these results. The ROC curve for percent
      change in H. pylori IgG-antibody titers had good diagnostic power in identifying
      H. pylori negative patients, with an area under the ROC curve of 0.70 (95 % CI
      0.59 to 0.79, P = 0.085) at 3 months and 0.83 (95% CI 0.76 to 0.89, P < 0.0001)
      at 12 months. A cut-off point of at least 21% decrease in H. pylori IgG-antibody
      titers at 3 months and 58% at 12 months provided a sensitivity of 64% and 87% and
      a specificity of 81% and 74% respectively, for successful eradication of H.
      pylori. CONCLUSIONS: In NSAID using patients, following H. pylori eradication
      therapy or placebo, histological examination of gastric mucosal tissue biopsies
      provided good sensitivity and specificity ratios for evaluating success of H.
      pylori eradication therapy. A percentual H. pylori IgG-antibody titer change has
      better sensitivity and specificity than an absolute titer change or a predefined
      H. pylori IgG-antibody titer cut-off point for evaluating success of H. pylori
      eradication therapy.

PMID- 23006809
TI  - Next-generation sequencing: path for driver discovery in hepatocellular
      carcinoma.

PMID- 23006808
TI  - Efficacy of auditory training using the auditory brainstem response to complex
      sounds: auditory processing disorder and specific language impairment.
AB  - OBJECTIVES: This study verified the efficacy of a formal auditory training (AT)
      program in children with hearing and language disorders using the auditory
      brainstem response to complex sounds (c-ABR) with and without background noise.
      PATIENTS AND METHODS: Thirty children (7-13 years) were distributed into four
      groups: typical development (TD: n = 7), auditory processing disorder (APD: n =
      9) and specific language disorder (SLIa: n = 6, and SLIb: n = 8). All children
      underwent behavioral assessment of auditory processing and c-ABR with and without
      background noise. The APD and SLIa groups underwent 8 weeks of formal AT, but all
      children were reevaluated 12 weeks after the initial assessment. RESULTS: The TD
      group presented better behavioral performance than the other groups. For c-ABR in
      silence, no significant differences were observed among groups or assessments,
      except regarding VA complex measures, which were altered in the APD group. For c
      ABR with background noise, however, the APD, SLIa and SLIb groups presented
      delayed latencies. Groups that underwent formal AT improved behavioral
      performance and decreased latencies to c-ABR in background noise at final
      assessment. CONCLUSIONS: These data suggest that efficacy of formal AT can be
      demonstrated by c-ABR with background noise.

PMID- 23006811
TI  - Influence of different performance levels on pacing strategy during the Women's
      World Championship marathon race.
AB  - PURPOSE: To analyze pacing strategies displayed by athletes achieving differing
      levels of performance during an elite-level marathon race. METHODS: Competitors
      in the 2009 IAAF Women's Marathon Championship were split into groups 1, 2, 3,
      and 4 comprising the first, second, third, and fourth 25% of finishers,
      respectively. Final, intermediate, and personal-best (PB) times of finishers were
      converted to mean speeds, and relative speed (% of PB speed) was calculated for
      intermediate segments. RESULTS: Mean PB speed decreased from groups 1 to 4, and
      speeds maintained in the race were 98.5% +/- 1.8%, 97.4% +/- 3.2%, 95.0% +/-
      3.1%, and 92.4% +/- 4.4% of PB speed for groups 1-4 respectively. Group 1 was
      fastest in all segments, and differences in speed between groups increased
      throughout the race. Group 1 ran at lower relative speeds than other groups for
      the first two 5-km segments but higher relative speeds after 35 km. Significant
      differences (P < .01) in the percentage of PB speed maintained were observed
      between groups 1 and 4 and groups 2 and 4 in all segments after 20 km and groups
      3 and 4 from 20 to 25 km and 30 to 35 km. CONCLUSIONS: Group 1 athletes achieved
      better finishing times relative to their PB than athletes in other groups, who
      selected unsustainable initial speeds resulting in subsequent significant losses
      of speed. It is suggested that psychological factors specific to a major
      competitive event influenced decision making by athletes, and poor decisions
      resulted in final performances inferior to those expected based on PB times.

PMID- 23006813
TI  - Low-molecular-weight adiponectin is more closely associated with episodes of
      asthma than high-molecular-weight adiponectin.
AB  - Adiponectin is divided into high-molecular-weight (HMW), middle-molecular-weight
      (MMW) and low-molecular-weight (LMW) types.  While HMW adiponectin has been
      studied by many researchers, the roles of MMW and LMW adiponectin have not yet
      been sufficiently elucidated.  In addition, there are conflicting findings
      regarding the role of adiponectin in chronic inflammatory diseases, especially
      asthma.  Therefore, we compared patients who suffered episodes of asthma in the
      past (=asthmatics) with those who did not (=non-asthmatics) in order to
      investigate the relationship between asthma and HMW, MMW and LMW adiponectin. 
      The subjects in this study included 76 university students.  None of the subjects
      were smokers, on regular medications or seeing a doctor regularly at the time. 
      Fourteen subjects reported past histories of asthma.  We also measured and
      compared the levels of leptin and ghrelin to that of adiponectin, as these
      hormones are connected with inflammatory conditions.  Although the physical data
      of the asthmatics were similar to those of the non-asthmatics, the levels of
      ghrelin and all fractions of adiponectin tended to be lower in the asthmatics
      than in the non-asthmatics.  While the levels of MMW and LMW adiponectin in the
      asthmatics were found to be significantly low, the levels of ghrelin and HMW
      adiponectin were not clear.  According to a multivariate regression analysis of
      the MMW and LMW adiponectin levels, asthma was found to be more significantly
      associated with the LMW adiponectin level than age, waist circumference or HDL-C.
      The results suggest that LMW adiponectin may be associated with episodes of
      asthma in males.

PMID- 23006812
TI  - Cardiac production of B-type natriuretic peptide is inversely related to the
      plasma level of free fatty acids in obese individuals - possible involvement of
      the insulin resistance -.
AB  - B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is
      increased with the severity of left ventricular (LV) dysfunction/hypertrophy. 
      The normal heart preferentially utilizes fatty acids as energy substrates. 
      Plasma BNP levels are reported to be lower in obese individuals.  We examined the
      relationship between BNP production and plasma free fatty acids (FFA),
      homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/
      hypertrophy.  We examined the plasma BNP levels and FFA at the aortic root (AO)
      and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men
      and 24 women, 62.5+/-11.7 yrs) who underwent cardiac catheterization.  Log BNP
      (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877,
      P<0.001).  Log BNP(CS-AO) had a significant negative correlation with BMI (r=
      0.558, P<0.001), waist circumference (WC) (r=-0.574, P<0.001), log FFA(AO) (r=
      0.643, P<0.001), log triglyceride (r=-0.431, P<0.001), and log HOMA-IR (r=-0.463,
      P<0.001) and a significant positive correlation with left ventricular mass index
      (LVMI) (r=0.403, P=0.001).  The multivariable regression analyses including log
      HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI
      were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and
      0.004, respectively).  We conclude that plasma BNP levels are determined
      primarily by cardiac production and that insulin resistance is a significant
      predictor of cardiac BNP production independent of LV hypertrophy in obese
      individuals.

PMID- 23006814
TI  - Early childhood tuberculosis in northwestern Tanzania.
AB  - SETTING: Data on pediatric tuberculosis (TB) from TB-endemic, resource
      constrained regions are limited, impacting awareness of disease burden and
      influencing diagnostic actions. OBJECTIVE: To obtain recorded incidence of
      childhood (age <5 years) TB in Mwanza Municipality, Tanzania, to estimate true
      incidence and to explore setting-specific reasons for differences. DESIGN:
      Recorded incidence of pediatric TB (2006-2010) was obtained from Mwanzan TB
      registries. Incident smear-positive pulmonary TB cases recruited from four TB
      clinics were used to estimate children exposed and the theoretical incidence of
      disease, assuming that either 10% or 23% of children would progress to disease
      following exposure. Reasons for underestimation were evaluated in the medical
      records of children who died at a secondary hospital. RESULTS: Between 2006 and
      2010, 279 early childhood TB cases were recorded (TB incidence 63/100,000/year).
      Over a 3-month period in 2011, 44% of smear-positive TB patients being treated in
      Mwanza were living with a total of 139 children. From census data, we estimated
      that 1279 children were exposed in Mwanza in 2011. Using estimates of the
      likelihood of disease progression, the theoretical incidence of early childhood
      TB ranged from 134.2 to 308.5/100,000/year. CONCLUSIONS: The true burden of early
      childhood TB is likely much higher than recorded. Age-specific reporting,
      increasing clinical awareness and screening may reduce the magnitude of
      underdiagnosis in this vulnerable population.

PMID- 23006816
TI  - Does modern helicopter construction reduce noise exposure in helicopter rescue
      operations?
AB  - BACKGROUND: During helicopter rescue operations the medical personnel are at high
      risk for hearing damage by noise exposure. There are two important factors to be
      taken into account: first, the extreme variability, with some days involving no
      exposure but other days with extreme exposure; second, the extreme noise levels
      during work outside the helicopter, e.g. during winch operations. The benefit of
      modern, less noisier constructions and the consequences for noise protection are
      still unknown. OBJECTIVES: We estimated the noise exposure of the personnel for
      different helicopter types used during rescue operations in the Alps and in other
      regions of the world with special regard to the advanced types like Eurocopter EC
      135 to compare the benefit of modern constructions for noise protection with
      earlier ones. METHODS: The rescue operations over 1 year of four rescue bases in
      the Alps (Raron and Zermatt in Switzerland; Landeck and Innsbruck in Austria, n =
      2731) were analyzed for duration of rescue operations (noise exposure). Noise
      levels were measured during rescue operations at defined points inside and
      outside the different aircraft. The setting is according to the European standard
      (Richtlinie 2003/10/EG Amtsblatt) and to Class 1 DIN/IEC 651. With both data sets
      the equivalent noise level L(eq8h) was calculated. For comparison it was assumed
      that all rescue operations were performed with a specific type of helicopter.
      Then model calculations for noise exposure by different helicopter types, such as
      Alouette IIIb, Alouette II 'Lama', Ecureuil AS350, Bell UH1D, Eurocopter EC135,
      and others were performed. RESULTS AND CONCLUSIONS: Depending on modern
      technologies the situation for the personnel has been improved significantly.
      Nevertheless noise prevention, which includes noise intermissions in spare time,
      is essential. Medical checks of the crews by occupational medicine (e.g. 'G20' in
      Germany) are still mandatory.

PMID- 23006817
TI  - Uncertainty in aspiration efficiency estimates from torso simplifications in
      computational fluid dynamics simulations.
AB  - Computational fluid dynamics (CFD) has been used to report particle inhalability
      in low velocity freestreams, where realistic faces but simplified, truncated, and
      cylindrical human torsos were used. When compared to wind tunnel velocity
      studies, the truncated models were found to underestimate the air's upward
      velocity near the humans, raising questions about aspiration estimation. This
      work compares aspiration efficiencies for particles ranging from 7 to 116 um
      using three torso geometries: (i) a simplified truncated cylinder, (ii) a non
      truncated cylinder, and (iii) an anthropometrically realistic humanoid body. The
      primary aim of this work is to (i) quantify the errors introduced by using a
      simplified geometry and (ii) determine the required level of detail to adequately
      represent a human form in CFD studies of aspiration efficiency. Fluid simulations
      used the standard k-epsilon turbulence models, with freestream velocities at 0.1,
      0.2, and 0.4 m s(-1) and breathing velocities at 1.81 and 12.11 m s(-1) to
      represent at-rest and heavy breathing rates, respectively. Laminar particle
      trajectory simulations were used to determine the upstream area, also known as
      the critical area, where particles would be inhaled. These areas were used to
      compute aspiration efficiencies for facing the wind. Significant differences were
      found in both vertical velocity estimates and the location of the critical area
      between the three models. However, differences in aspiration efficiencies between
      the three forms were <8.8% over all particle sizes, indicating that there is
      little difference in aspiration efficiency between torso models.

PMID- 23006818
TI  - Functional recovery in rat spinal cord injury induced by hyperbaric oxygen
      preconditioning.
AB  - BACKGROUND: It is a common belief that neurosurgical interventions can cause
      inevitable damage resulting from the procedure itself in surgery especially for
      intramedullary spinal cord tumors. The present study was designed to examine if
      hyperbaric oxygen preconditioning (HBO-PC)  was neuroprotective against surgical
      injuries using a rat model of spinal cord injury (SCI). METHODS: Sprague-Dawley
      rats were randomly divided into three groups: HBO-PC group, hypobaric hypoxic
      preconditioning (HH-PC) control group, and normobaric control group. All groups 
      were subjected to SCI by weight drop device. Rats from each group were examined
      for neurological behavior and electrophysiological function. Tissue sections were
      analyzed by using immunohistochemistry, TdT-mediated dUTP-biotin nick end
      labeling, and axonal tract tracing. RESULTS: Significant neurological deficits
      were observed after SCI and HBO-PC and HH-PC improved neurological deficits 1
      week post-injury. The latencies of motor-evoked potential and somatosensory
      evoked potential were significantly delayed after SCI, which was attenuated by
      HBO-PC and HH-PC. Compared  with normobaric control group, pretreatment with HBO
      and hypobaric hypoxia significantly reduced the number of TdT-mediated dUTP
      biotin nick end labeling-positive cells, and increased nestin-positive cells. HBO
      PC and HH-PC enhanced axonal growth after SCI. CONCLUSIONS: In conclusion, 
      preconditioning with HBO and hypobaric hypoxia can facilitate functional recovery
      and suppress cell apoptosis after SCI and may prove to be a useful preventive
      strategy to neurosurgical SCI.

PMID- 23006820
TI  - Design of peptidomimetics for inhibition of HER2 receptor dimerization by a
      combination of virtual screening, MD simulations, and QSAR in silico methods.
AB  - Malfunction or overexpression of ErbB receptors (epidermal growth factor
      receptors) is associated with occurrence and severity of several types of cancer.
      Initiation of signal cascades by ErbB2 (also known as human epidermal growth
      factor receptor 2/neu) in breast cancer has been blocked by monoclonal antibodies
      such as Trastuzumab (Herceptin), which interact with the extracellular domain of
      human epidermal growth factor receptor 2. Due to some disadvantages of monoclonal
      antibodies, a new approach in blocking human epidermal growth factor receptor 2
      dimerization and activation is designing peptidomimetic ligands based on human
      epidermal growth factor receptor 2-Trastuzumab interaction model. Growth of human
      epidermal growth factor receptor 2(+) SK-BR3 cells could be specifically
      inhibited by peptidomimetic herceptin-based peptidomimetic 5. In this study,
      herceptin-based peptidomimetic 5 was used as a benchmark peptidomimetic compound
      to perform a ligand-based virtual screening followed by structure-based screening
      by applying the molecular docking approach. The study aimed to explore more
      potent peptidomimetic molecules against extracellular part of human epidermal
      growth factor receptor 2. Our results showed that the newly designed
      peptidomimetic herceptin-based peptidomimetic n33B in comparison with herceptin
      based peptidomimetic 5 binds more tightly to the extracellular domain of human
      epidermal growth factor receptor 2. Mechanistic aspects of herceptin-based
      peptidomimetic n33B interaction with human epidermal growth factor receptor 2
      were more investigated through 20-ns molecular dynamic simulations. Additionally,
      a quantitative structure-activity relationships study was performed to develop a
      model for identification of structural determinants in herceptin-based
      peptidomimetic 5-based peptidomimetics.

PMID- 23006821
TI  - The internet, teenagers, and sexual health information: a cautionary tale.
AB  - Although most Israeli teenagers have access to the web and many have used the
      internet to obtain health information, they do not have access to accurate and
      complete information about contraceptives on Hebrew language websites. Indeed
      other evidence suggests that teens do not use the web frequently for health
      information, they are wary of the information obtained from internet sites, and
      the search engines that they use may not lead them to the most helpful resources.
      While the internet has the capacity to provide teenagers with information which
      can assist them in preventing unintended pregnancy and sexually transmitted
      infections, interventions that address these challenges need to be developed and
      rigorously tested.

PMID- 23006819
TI  - Telomeres-structure, function, and regulation.
AB  - In mammals, maintenance of the linear chromosome ends (or telomeres) involves
      faithful replication of genetic materials and protection against DNA damage
      signals, to ensure genome stability and integrity. These tasks are carried out by
      the telomerase holoenzyme and a unique nucleoprotein structure in which an array
      of telomere-associated proteins bind to telomeric DNA to form special protein/DNA
      complexes. The telomerase complex, which is comprised of telomeric reverse
      transcriptase (TERT), telomeric RNA component (TERC), and other assistant
      factors, is responsible for adding telomeric repeats to the ends of chromosomes.
      Without proper telomere maintenance, telomere length will shorten with successive
      round of DNA replication due to the so-called end replication problem. Aberrant
      regulation of telomeric proteins and/or telomerase may lead to abnormalities that
      can result in diseases such as dyskeratosis congenita (DC) and cancers.
      Understanding the mechanisms that regulate telomere homeostasis and the factors
      that contribute to telomere dysfunction should aid us in developing diagnostic
      and therapeutic tools for these diseases.

PMID- 23006822
TI  - Distribution of psychiatric symptoms among young Turkish males and the
      relationship between these symptoms and socio-demographic characteristics.
AB  - OBJECTIVE: Youth is a period during which individuals undergo rapid physical and
      psychological changes in their transition from childhood to adulthood. This study
      aimed to determine the psychological problems of young males from different socio
      cultural backgrounds living in different cities of Turkey and to examine the
      socio-cultural factors possibly associated with these problems. METHODS: The
      study was conducted in six different cities in Turkey with the participation of
      3655 young male adults. Participants were administered a questionnaire to collect
      socio-demographic data such as age, marital status, educational background, the
      history of smoking and alcohol use, income level, occupation, place of residence
      and the history of chronic disease and allergies. Psychological symptoms were
      detected via the Symptom Check List (SCL-90 R). The study data were transferred
      to the SPSS-15 database for statistical analysis. RESULTS: The median age of the
      participants was 20.49+/-1.48years (20-29 age range, median age=20). Based on the
      SCL-90 R scores, the mean General Symptom Index (GSI) score of the study
      participants was found to be 0.44+/-0.27 (0.00-2.61). 13.5% of the participants
      (n=493) were recorded to have above-the-average GSI scores (>=1.0). Occupation,
      smoking and alcohol use were found to effect depression. Factors effecting
      anxiety were occupation, smoking, alcohol use and place of residence. CONCLUSION:
      Psychological symptoms that young people suffer from can be diagnosed at early
      stages and the psychological problems that are triggered by these symptoms can be
      prevented with the help of such questionnaires. These questionnaires can easily
      be administered in primary care settings.

PMID- 23006823
TI  - The effect of daily fluoride mouth rinsing on enamel erosive/abrasive wear in
      situ.
AB  - It is not known whether application of fluoride agents on enamel results in
      lasting resistance to erosive/abrasive wear. We investigated if one daily mouth
      rinse with sodium fluoride (NaF), stannous fluoride (SnF(2)) or titanium
      tetrafluoride (TiF(4)) solutions protected enamel against erosive/abrasive wear
      in situ (a paired, randomised and blind study). Sixteen molars were cut into 4
      specimens, each with one amalgam filling (measurement reference surface). Two
      teeth (2 * 4 specimens) were mounted bilaterally (buccal aspects) on acrylic
      mandibular appliances and worn for 9 days by 8 volunteers. Every morning, the
      specimens were brushed manually with water (30 s) extra-orally. Then fluoride
      solutions (0.4% SnF(2) pH 2.5; 0.15% TiF(4) pH 2.1; 0.2% NaF pH 6.5, all 0.05 M
      F) were applied (2 min). Three of the specimens from each tooth got different
      treatment, and the fourth served as control. At midday, the specimens were etched
      for 2 min in 300 ml fresh 0.01 M hydrochloric acid and rinsed in tap water. This
      etch procedure was repeated in the afternoon. Topographic measurements were
      performed by a white-light interferometer. Mean surface loss (+/-SD) for 16 teeth
      after 9 days was: SnF(2) 1.8 +/- 1.9 um, TiF(4) 3.1 +/- 4.8 um, NaF 26.3 +/- 4.7
      um, control 32.3 +/- 4.4 um. Daily rinse with SnF(2), TiF(4) and NaF resulted in
      94, 90 and 18% reduction in enamel erosive/abrasive wear, respectively, compared
      with control (p < 0.05). The superior protective effect of daily rinse with
      either stannous or titanium tetrafluoride solutions on erosive/abrasive enamel
      wear is promising.

PMID- 23006824
TI  - Team-based learning applied to a medicinal chemistry course.

PMID- 23006825
TI  - Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian
      cells.
AB  - BACKGROUND: The function of RNA from the non-coding (the so called "dark matter")
      regions of the genome has been a subject of considerable recent debate. Perhaps
      the most controversy is regarding the function of RNAs found in introns of
      annotated transcripts, where most of the reads that map outside of exons are
      usually found. However, it has been reported that the levels of RNA in introns
      are minor relative to those of the corresponding exons, and that changes in the
      levels of intronic RNAs correlate tightly with that of adjacent exons. This would
      suggest that RNAs produced from the vast expanse of intronic space are just
      pieces of pre-mRNAs or excised introns en route to degradation. RESULTS: We
      present data that challenges the notion that intronic RNAs are mere by-standers
      in the cell. By performing a highly quantitative RNAseq analysis of transcriptome
      changes during an inflammation time course, we show that intronic RNAs have a
      number of features that would be expected from functional, standalone RNA
      species. We show that there are thousands of introns in the mouse genome that
      generate RNAs whose overall abundance, which changes throughout the inflammation
      timecourse, and other properties suggest that they function in yet unknown ways.
      CONCLUSIONS: So far, the focus of non-coding RNA discovery has shied away from
      intronic regions as those were believed to simply encode parts of pre-mRNAs.
      Results presented here suggest a very different situation--the sequences encoded
      in the introns appear to harbor a yet unexplored reservoir of novel, functional
      RNAs. As such, they should not be ignored in surveys of functional transcripts or
      other genomic studies.

PMID- 23006826
TI  - Why are family carers of people with dementia dissatisfied with general hospital
      care? A qualitative study.
AB  - BACKGROUND: Families and other carers report widespread dissatisfaction with
      general hospital care for confused older people. METHODS: We undertook a
      qualitative interviews study of 35 family carers of 34 confused older patients to
      ascertain their experiences of care on geriatric and general medical, and
      orthopaedic wards of a large English hospital. Transcripts were analysed using a
      grounded theory approach. Themes identified in interviews were categorised, and
      used to build a model explaining dissatisfaction with care. RESULTS: The
      experience of hospital care was often negative. Key themes were events (illness
      leading to admission, experiences in the hospital, adverse occurrences including
      deterioration in health, or perceived poor care); expectations (which were
      sometimes unrealistic, usually unexplored by staff, and largely unmet from the
      carers' perspective); and relationships with staff (poor communication and
      conflict over care). Expectations were influenced by prior experience. A cycle of
      discontent is proposed. Events (or 'crises') are associated with expectations.
      When these are unmet, carers become uncertain or suspicious, which leads to a
      period of 'hyper vigilant monitoring' during which carers seek out evidence of
      poor care, culminating in challenge, conflict with staff, or withdrawal, itself a
      crisis. The cycle could be completed early during the admission pathway, and
      multiple cycles within a single admission were seen. CONCLUSION: People with
      dementia who have family carers should be considered together as a unit. Family
      carers are often stressed and tired, and need engaging and reassuring. They need
      to give and receive information about the care of the person with dementia, and
      offered the opportunity to participate in care whilst in hospital. Understanding
      the perspective of the family carer, and recognising elements of the 'cycle of
      discontent', could help ward staff anticipate carer needs, enable relationship
      building, to pre-empt or avoid dissatisfaction or conflict.

PMID- 23006827
TI  - Histamine excites rat superior vestibular nuclear neurons via postsynaptic H1 and
      H2 receptors in vitro.
AB  - The superior vestibular nucleus (SVN), which holds a key position in vestibulo
      ocular reflexes and nystagmus, receives direct hypothalamic histaminergic
      innervations. By using rat brainstem slice preparations and extracellular unitary
      recordings, we investigated the effect of histamine on SVN neurons and the
      underlying receptor mechanisms. Bath application of histamine evoked an
      excitatory response of the SVN neurons, which was not blocked by the low
      Ca(2+)/high-Mg(2+) medium, indicating a direct postsynaptic effect of the amine.
      Selective histamine H1 receptor agonist 2-pyridylethylamine and H2 receptor
      agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked
      the excitation of histamine on SVN neurons. In addition, selective H1 receptor
      antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120,
      a selective H4 receptor antagonist, partially blocked the excitatory response of
      SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly
      totally blocked the histamine-induced excitation. Immunostainings further showed
      that histamine H1 and H2 instead of H4 receptors existed in the SVN. These
      results demonstrate that histamine excites the SVN neurons via postsynaptic
      histamine H1 and H2 receptors, and suggest that the central histaminergic
      innervation from the hypothalamus may actively bias the SVN neuronal activity and
      subsequently modulate the SVN-mediated vestibular functions and gaze control.

PMID- 23006828
TI  - Positive hepatitis B surface antigen tests due to recent vaccination: a
      persistent problem.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a common cause of viral hepatitis with
      significant health complications including cirrhosis and hepatocellular
      carcinoma. Assays for hepatitis B surface antigen (HBsAg) are the most frequently
      used tests to detect HBV infection. Vaccination for HBV can produce transiently
      detectable levels of HBsAg in patients. However, the time course and duration of
      this effect is unclear. The objective of this retrospective study was to clarify
      the frequency and duration of transient HBsAg positivity following vaccination
      against HBV. METHODS: The electronic medical record at an academic tertiary care
      medical center was searched to identify all orders for HBsAg within a 17 month
      time period. Detailed chart review was performed to identify all patients who
      were administered HBV vaccine within 180 days prior to HBsAg testing and also to
      ascertain likely cause of weakly positive (grayzone) results. RESULTS: During the
      17 month study period, 11,719 HBsAg tests were ordered on 9,930 patients. There
      were 34 tests performed on 34 patients who received HBV vaccine 14 days or less
      prior to HBsAg testing. Of these 34 patients, 11 had grayzone results for HBsAg
      that could be attributed to recent vaccination. Ten of the 11 patients were renal
      dialysis patients who were receiving HBsAg testing as part of routine and ongoing
      monitoring. Beyond 14 days, there were no reactive or grayzone HBsAg tests that
      could be attributed to recent HBV vaccination. HBsAg results reached a peak COI
      two to three days following vaccination before decaying. Further analysis of all
      the grayzone results within the 17 month study period (43 results out of 11,719
      tests) revealed that only 4 of 43 were the result of true HBV infection as
      verified by confirmatory testing. CONCLUSIONS: Our study confirms that transient
      HBsAg positivity can occur in patients following HBV vaccination. The results
      suggest this positivity is unlikely to persist beyond 14 days post-vaccination.
      Our study also demonstrates that weakly positive HBsAg results often do not
      reflect actual HBV infection, underscoring the importance of confirmatory
      testing. This study also emphasizes that vaccination-induced HBsAg positives
      occur most commonly in hemodialysis patients.

PMID- 23006829
TI  - Epithelial-smooth muscle cooperation is needed for brain natriuretic peptide
      dependent bronchorelaxant activity.

PMID- 23006830
TI  - Adherence to preferable behavior for lipid control by high-risk dyslipidemic
      Japanese patients under pravastatin treatment: the APPROACH-J study.
AB  - AIM: We evaluated the impact of adherence to preferable behavior on serum lipid
      control assessed by a self-reported questionnaire in high-risk patients taking
      pravastatin for primary prevention of coronary artery disease. METHODS: High-risk
      patients taking pravastatin were followed for 2 years. Questionnaire surveys
      comprising 21 questions, including 18 questions concerning awareness of health,
      and current status of diet, exercise, and drug therapy, were conducted at
      baseline and after 1 year. Potential domains were established by factor analysis
      from the results of questionnaires, and adherence scores were calculated in each
      domain. The relationship between adherence scores and lipid values during the 1
      year treatment period was analyzed by each domain using multiple regression
      analysis. RESULTS: A total of 5,792 patients taking pravastatin were included in
      the analysis. Multiple regression analysis showed a significant correlation in
      terms of "Intake of high fat/cholesterol/sugar foods" (regression coefficient 
      0.58, p=0.0105) and "Adherence to instructions for drug therapy" (regression
      coefficient -6.61, p<0.0001). Low-density lipoprotein cholesterol (LDL-C) values
      were significantly lower in patients who had an increase in the adherence score
      in the "Awareness of health" domain compared with those with a decreased score.
      There was a significant correlation between high-density lipoprotein (HDL-C)
      values and "Awareness of health" (regression coefficient 0.26; p= 0.0037),
      "Preferable dietary behaviors" (regression coefficient 0.75; p<0.0001), and
      "Exercise" (regression coefficient 0.73; p= 0.0002). Similar relations were seen
      with triglycerides. CONCLUSION: In patients who have a high awareness of their
      health, a positive attitude toward lipid-lowering treatment including diet,
      exercise, and high adherence to drug therapy, is related with favorable overall
      lipid control even in patients under treatment with pravastatin.

PMID- 23006831
TI  - Transcriptomic analysis of the oleaginous microalga Neochloris oleoabundans
      reveals metabolic insights into triacylglyceride accumulation.
AB  - BACKGROUND: The lack of sequenced genomes for oleaginous microalgae limits our
      understanding of the mechanisms these organisms utilize to become enriched in
      triglycerides. Here we report the de novo transcriptome assembly and quantitative
      gene expression analysis of the oleaginous microalga Neochloris oleoabundans,
      with a focus on the complex interaction of pathways associated with the
      production of the triacylglycerol (TAG) biofuel precursor. RESULTS: After growth
      under nitrogen replete and nitrogen limiting conditions, we quantified the
      cellular content of major biomolecules including total lipids, triacylglycerides,
      starch, protein, and chlorophyll. Transcribed genes were sequenced, the
      transcriptome was assembled de novo, and the expression of major functional
      categories, relevant pathways, and important genes was quantified through the
      mapping of reads to the transcriptome. Over 87 million, 77 base pair high quality
      reads were produced on the Illumina HiSeq sequencing platform. Metabolite
      measurements supported by genes and pathway expression results indicated that
      under the nitrogen-limiting condition, carbon is partitioned toward triglyceride
      production, which increased fivefold over the nitrogen-replete control. In
      addition to the observed overexpression of the fatty acid synthesis pathway, TAG
      production during nitrogen limitation was bolstered by repression of the beta
      oxidation pathway, up-regulation of genes encoding for the pyruvate dehydrogenase
      complex which funnels acetyl-CoA to lipid biosynthesis, activation of the pentose
      phosphate pathway to supply reducing equivalents to inorganic nitrogen
      assimilation and fatty acid biosynthesis, and the up-regulation of lipases
      presumably to reconstruct cell membranes in order to supply additional fatty
      acids for TAG biosynthesis. CONCLUSIONS: Our quantitative transcriptome study
      reveals a broad overview of how nitrogen stress results in excess TAG production
      in N. oleoabundans, and provides a variety of genetic engineering targets and
      strategies for focused efforts to improve the production rate and cellular
      content of biofuel precursors in oleaginous microalgae.

PMID- 23006832
TI  - Natriuretic peptide proANP (1-98), a biomarker of ALI/ARDS in burns.
AB  - INTRODUCTION: Plasma atrial natriuretic peptide levels (proANP (1-98)), a
      parameter of myocardial dysfunction, have been reported to be increased in
      critically ill patients with acute lung injury/acute respiratory distress
      syndrome (ALI/ARDS). The aim of the study was to examine if proANP is a biomarker
      of ALI/ARDS as assessed by the Sequential Organ Failure Assessment score (SOFA
      Lung >=2) in burn patients, and how it compares to the corresponding values for
      age, total body surface area percent (TBSA%) and inhalation injury for mortality
      prediction. METHODS: A group of 22 burn patients with a mean TBSA of 30% (10-75%)
      and a mean age of 52 years (25-84 years) was investigated during 2010. Organ
      dysfunction/failure was classified according to the SOFA score. The criteria for
      ALI/ARDS were based on SOFA Lung >=2. ProANP (1-98) concentrations (nmoll(-1))
      were measured by commercially available enzyme linked immunosorbent assay (ELISA)
      immunoassays (Biomedica Austria) on post-burn days 2 and 7. RESULTS: ProANP
      levels on day 7 post-burn positively correlated with a SOFA score day 7 post
      burn, c=0.91. The receiver operating curve (ROC) analysis proved a sensitivity of
      75% and a specificity of 75% for ALI/ARDS at cut-off values >3.35 nmoll(-1). The
      ROC value of proANP for ALI/ARDS (SOFA Lung >=2) was significantly larger than
      that of age, TBSA% and inhalation injury: 0.90, 0.71, 0.74, and 0.69 (p<0.001).
      CONCLUSIONS: ProANP levels, as a biomarker of ALI/ARDS, in critically burn
      patients correlated with SOFA scoring. The inhalation injury did not lead to
      increase in proANP values.

PMID- 23006833
TI  - An approach to estimating gross efficiency during high-intensity exercise.
AB  - PURPOSE: Gross efficiency (GE) is coupling power production to propulsion and is
      an important performance-determining factor in endurance sports. Measuring GE
      normally requires measuring VO(2) during submaximal exercise. In this study a
      method is proposed to estimating GE during high-intensity exercise. METHODS:
      Nineteen subjects completed a maximal incremental test and 2 GE tests (1
      experimental and 1 control test). The GE test consisted of 10 min cycling at 50%
      peak power output (PPO), 2 min at 25 W, followed by 4 min 100% PPO, 1 min at 25
      W, and another 10 min at 50% PPO. GE was determined for the 50%-PPO sections and
      was, for the second 50%-PPO section, back-extrapolated, using linear regression,
      to the end of the 100%-PPO bout. RESULTS: Back-extrapolation of the GE data
      resulted in a calculated GE of 15.8% +/- 1.7% at the end of the 100%-PPO bout, in
      contrast to 18.3% +/- 1.3% during the final 2 min of the first 10-min 50%-PPO
      bout. CONCLUSION: Back-extrapolation seems valuable in providing more insight in
      GE during high-intensity exercise.

PMID- 23006834
TI  - Cost comparison of wirelessly vs. directly observed therapy for adherence
      confirmation in anti-tuberculosis treatment.
AB  - SETTING: A US clinic treating patients entering the continuation phase of
      treatment for Mycobacterium tuberculosis. OBJECTIVE: To compare the costs of
      direct confirmation of treatment using wirelessly observed therapy (WOT) vs.
      standard of care utilizing World Health Organization-recommended  7-day and 3-day
      directly observed therapy (DOT). DESIGN: A model was created comparing the costs
      between the two types of DOT and WOT, using data from public sources of
      treatment, personnel costs, patient spending, and interview responses. The model
      considered public health facility's cost-to-treat  and patient's cost-to-be
      treated. Cost drivers for M. tuberculosis treatment monitoring were identified,
      and four univariate sensitivity analyses were conducted on selected variables.
      RESULTS: The cost of WOT was estimated to be 36% of 7-day DOT, and 71% of 3-day
      DOT in public health  facility's cost-to-treat. The patient's cost-to-be-treated
      with WOT was estimated to be 4% of 7-day DOT and 8% of 3-day DOT. Sensitivity
      analyses indicated that WOT was likely to provide immediate cost savings over a
      range of WOT costs, time spent on WOT monitoring, WOT-related treatment failure 
      rates and clinician compensations. CONCLUSION: Under several potential cost
      scenarios, the immediate cost of M. tuberculosis treatment by WOT appears to be
      substantially less than DOT. Further WOT development for M. tuberculosis
      treatment appears warranted.

PMID- 23006835
TI  - A synonymous mutation in LMAN1 creates an ectopic splice donor site and causes
      combined deficiency of FV and FVIII.

PMID- 23006837
TI  - Pediatric intracardiac thrombus: a diagnostic and therapeutic dilemma.
AB  - This case highlights the challenges in treating children with intracardiac
      thrombosis. We describe a teenager who developed an unsuspected de novo
      intracardiac thrombus. She was treated initially medically and surgically, but
      required subsequent surgery to treat a life-threatening recurrence. This case
      demonstrates an unusual presentation, as well as imaging, diagnostic, and
      therapeutic dilemmas. More significantly, it emphasizes the importance of a
      multidisciplinary approach for successful treatment of intracardiac thrombus. 

PMID- 23006836
TI  - What is the prevalence of musculoskeletal problems in the elderly population in
      developed countries? A systematic critical literature review.
AB  - BACKGROUND: The proportion of older people will be tripled by the year 2050. In
      addition, the incidence of chronic musculoskeletal (MSK) conditions will also
      increase among the elderly people. Thus, in order to prepare for future health
      care demands, the magnitude and impact of MSK conditions from this growing
      population is needed. The objective of this literature review is to determine the
      current prevalence of MSK disorders in the elderly population. METHODS: A
      systematic literature search was conducted in Pubmed on articles in English,
      published between January 2000 and July 2011. Studies from developed countries
      with prevalence estimates on elderly people (60+) on the following MSK conditions
      were included: Non-specific extremity pain, rheumatoid arthritis, osteoarthritis,
      osteoporosis, and back pain. The included articles were extracted for information
      and assessed for risk of bias. RESULTS: A total of 85 articles were included with
      173 different prevalence estimates. Musculoskeletal disorders are common in the
      elderly population, but due to heterogeneity of the studies, no general estimate
      on the prevalence of MSK can be determined. Women report more often MSK pain than
      men. Overall, prevalence estimates either remain fairly constant or increase
      slightly with increasing age, but with a tendency to decrease in the oldest (80+)
      people. CONCLUSIONS: Musculoskeletal disorders remain prevalent in the elderly
      population. Given the increasing proportion of elderly population in the world
      population and the burden of MSK diseases among the elderly people, efforts must
      be made to maintain their functional capacity for as long as possible through
      optimal primary and secondary health care.

PMID- 23006839
TI  - Are there different criteria affecting prevalence of impaired glucose regulation
      as cardiometabolic risk factors in young adults other than BMI and waist
      circumference?.

PMID- 23006840
TI  - Remodelling of vascular (surgical) services in the UK.
AB  - The last few years have seen major changes in the delivery of vascular services
      in the UK. An increasingly elderly population with greater expectations from
      their medical services has challenged established methods. It also became
      apparent that outcomes for low volume, high risk index vascular interventions
      such as abdominal aortic aneurysm repair were poor in the UK compared to the rest
      of Europe. Other ongoing challenges were the introduction of a national aortic
      aneurysm screening programme and the development of vascular surgery as a
      separate speciality. This article details the approach taken to modernise
      vascular services in the UK, using a quality framework agreed by vascular
      specialists, which drove the structural change to move vascular interventions
      into fewer, higher volume centres. The introduction of modern networks is
      designed to maintain services in surrounding hospitals without on site vascular
      inpatient services. The initial effects of this service remodelling are positive,
      with elective aortic aneurysm mortality rates falling nationally from 7.5 to 2.4
      per cent.

PMID- 23006841
TI  - The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid
      metabolite-mediated peripheral inflammatory pain.
AB  - BACKGROUND: Oxidized linoleic acid metabolites (OLAMs) are a class of endogenous
      agonists to the transient receptor potential V1 (TRPV1) receptor. Although TRPV1
      mediates inflammatory heat hyperalgesia, it is not known if the OLAMs contribute
      to the peripheral activation of this receptor during tissue inflammation. In the
      present study, we evaluated whether the OLAM system is activated during
      inflammation and whether cytochrome P450 enzymes mediate OLAM contributions to
      heat hyperalgesia using the complete Freund's adjuvant (CFA) model of
      inflammation. RESULTS: Our results demonstrate that the intraplantar (ipl)
      injection of anti-OLAM antibodies significantly reversed CFA-induced heat
      hyperalgesia. Moreover, application of lipid extracts from inflamed rat skin to
      cultured sensory neurons triggered a significant release of iCGRP that is blocked
      by co-treatment with I-RTX, a TRPV1 antagonist. To determine the role of CYP
      enzymes in mediating OLAM effects, we used a broad spectrum CYP inhibitor,
      ketoconazole. Pretreatment with ketoconazole inhibited the release of TRPV1
      agonists in lipid extracts from inflamed skin and significantly reversed CFA
      induced heat hyperalgesia by a peripheral mechanism of action. Moreover, the ipl
      injection of linoleic acid to rats 24 hr after CFA evoked spontaneous nocifensive
      behaviors that were significantly reduced by capsazepine, by knockout of the
      TRPV1 gene, or by pretreatment with either anti-OLAM antibodies or ketoconazole.
      CONCLUSIONS: Taken together, our data suggests that OLAMs contribute to
      inflammatory nociception in the periphery and that cytochrome P450 enzymes play a
      crucial role in mediating OLAM contributions to inflammatory heat hyperalgesia.

PMID- 23006842
TI  - The involvement of Nrf2-ARE pathway in regulation of apoptosis in human
      glioblastoma cell U251.
AB  - OBJECTIVES: NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE)
      pathway plays anti-apoptotic role in normal tissue and tumor. But the role of
      Nrf2 in apoptosis in glioma is still unknown. Here, we established this
      experiment to elucidate how Nrf2-ARE  pathway participates in apoptosis in human
      glioblastoma cell U251. METHODS: Two plasmids, pEGFP-Nrf2 and Si-Nrf2, were
      transfected to up- or downregulate the expression of Nrf2 in U251. After
      transfection, the apoptosis rate, expression of heme oxygenase-1 (HO-1), Bcl-2,
      Bax, caspases  3, 9 and activity of caspases 3, 9 were detected. RESULTS: After
      increasing expression of Nrf2, the apoptosis rate was reduced accompanied with
      upregulated expression of HO-1, Bcl-2/Bax, decreased expression and activity of
      caspases 3, 9. After decreasing expression of Nrf2, the  apoptosis rate was
      enhanced accompanied with downregulated expression of HO-1, Bcl-2/Bax, increased
      expression and activity of caspases 3, 9. DISCUSSION: Our findings suggest that
      Nrf2 participates in the regulation of apoptosis in U251 through HO-1 and the
      'intrinsic'  apoptotic pathway.

PMID- 23006843
TI  - Comparative exome sequencing of metastatic lesions provides insights into the
      mutational progression of melanoma.
AB  - BACKGROUND: Metastasis is characterized by spreading of neoplastic cells to an
      organ other than where they originated and is the predominant cause of death
      among cancer patients. This holds true for melanoma, whose incidence is
      increasing more rapidly than any other cancer and once disseminated has few
      therapeutic options. Here we performed whole exome sequencing of two sets of
      matched normal and metastatic tumor DNAs. RESULTS: Using stringent criteria, we
      evaluated the similarities and differences between the lesions. We find that in
      both cases, 96% of the single nucleotide variants are shared between the two
      metastases indicating that clonal populations gave rise to the distant
      metastases. Analysis of copy number variation patterns of both metastatic sets
      revealed a trend similar to that seen with our single nucleotide variants.
      Analysis of pathway enrichment on tumor sets shows commonly mutated pathways
      enriched between individual sets of metastases and all metastases combined.
      CONCLUSIONS: These data provide a proof-of-concept suggesting that individual
      metastases may have sufficient similarity for successful targeting of driver
      mutations.

PMID- 23006844
TI  - Socio-economic inequalities in health care utilisation in Norway: a population
      based cross-sectional survey.
AB  - BACKGROUND: Norway provides universal health care coverage to all residents, but
      socio-economic inequalities in health are among the largest in Europe. Evidence
      on inequalities in health care utilisation is sparse, and the aim of this
      population based study was to investigate socio-economic inequalities in the
      utilisation of health care services in Tromso, Norway. METHODS: We used
      questionnaire data from the cross-sectional Tromso Study, conducted in 2007-8.
      All together 12,982 persons aged 30-87 years participated with the response rate
      of 65.7%. This is slightly more than one third of the total population (33.8%) in
      the mentioned age group in Tromso municipality. By logistic regression analyses
      we studied associations between household income, education and self-rated
      occupational status and the utilisation of general practitioner, somatic and
      psychiatric specialist outpatient services. The outcome variables were
      probability and frequency of use during the previous 12 months. Analyses were
      stratified by gender and adjusted for age, marital status, and self-rated health.
      RESULTS: Self-rated health was the dominant predictor of health care utilisation.
      Women's probability of visiting a general practitioner did not vary by socio
      economic status, but high income was associated with less frequent use (odds
      ratio [OR] for trend 0.89, 95% confidence interval [CI] 0.81-0.98). In men, high
      income predicted lower probability and frequency of general practitioner
      utilisation (OR for trend 0.85, CI 0.76-0.94, and 0.86, 0.78-0.95, respectively).
      Women's probability of visiting a somatic specialist increased with higher income
      (OR for trend 1.11, CI 1.01-1.21) and higher education (OR for trend 1.27, CI
      1.16-1.39). We found the same trends for men, though significant only for
      education (OR for trend 1.14, CI 1.05-1.25). The likelihood of visiting
      psychiatric specialist services increased with higher education and decreased
      with higher income in women (OR for trend 1.57, CI 1.24-1.98, and 0.69, 0.56
      0.86, respectively), but did not vary significantly by socio-economic variables
      in men. Higher income predicted more frequent use of psychiatric specialist
      services in men (OR for trend 2.02, CI 1.12-3.63). CONCLUSIONS: This study
      revealed important inequalities in the utilisation of health care services in
      Norway, inequalities which may contribute to sustaining inequalities in health
      outcomes.

PMID- 23006847
TI  - Transient deficiency of dendritic cells results in lack of a merozoite surface
      protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood
      stage infection.
AB  - Splenic dendritic cells are crucial for controlling the immune response to
      malaria by initiating a CD4 gamma interferon (IFN-gamma) response early in a
      blood-stage infection, which contributes to parasite clearance as well as to
      acute-stage immunopathology. CD8(-) CD11c(high) dendritic cells have been
      described previously to be important antigen-presenting cells for induction of
      these CD4 T cell responses in the spleens of Plasmodium chabaudi-infected mice.
      However, when isolated during the period of maximum parasitemia and shortly
      thereafter, the dendritic cells transiently lose their ability to stimulate T
      cells, recovering only as the parasitemia is controlled. This loss of a CD4 T
      cell response is also observed in vivo during this part of the infection. CD4 T
      cells from a T cell receptor-transgenic mouse recognizing a peptide of merozoite
      surface protein 1 (MSP1) injected into BALB/c mice during peak parasitemia
      proliferate poorly, and very few cells produce IFN-gamma and interleukin-2 (IL
      2), compared with transgenic T cells injected earlier in the blood-stage
      infection. CD8(-) dendritic cells at day 10 can process and present peptides on
      major histocompatibility complex (MHC) class II with an efficiency similar to
      that of dendritic cells from earlier in infection. The failure of the day 10
      dendritic cells to activate MSP1-specific CD4 T cells fully in vitro is
      associated with reduced expression of CD86 and lower production of IL-12 rather
      than with induction of inhibitory DC receptors or production of IL-10.

PMID- 23006848
TI  - Crucial role of gamma interferon-producing CD4+ Th1 cells but dispensable
      function of CD8+ T cell, B cell, Th2, and Th17 responses in the control of
      Brucella melitensis infection in mice.
AB  - Brucella spp. are facultative intracellular bacterial pathogens responsible for
      brucellosis, a worldwide zoonosis that causes abortion in domestic animals and
      chronic febrile disease associated with serious complications in humans. There is
      currently no approved vaccine against human brucellosis, and antibiotic therapy
      is long and costly. Development of a safe protective vaccine requires a better
      understanding of the roles played by components of adaptive immunity in the
      control of Brucella infection. The importance of lymphocyte subsets in the
      control of Brucella growth has been investigated separately by various research
      groups and remains unclear or controversial. Here, we used a large panel of
      genetically deficient mice to compare the importance of B cells, transporter
      associated with antigen processing (TAP-1), and major histocompatibility complex
      class II-dependent pathways of antigen presentation as well as T helper 1 (Th1),
      Th2, and Th17-mediated responses on the immune control of Brucella melitensis 16
      M infection. We clearly confirmed the key function played by gamma interferon
      (IFN-gamma)-producing Th1 CD4(+) T cells in the control of B. melitensis
      infection, whereas IFN-gamma-producing CD8(+) T cells or B cell-mediated humoral
      immunity plays only a modest role in the clearance of bacteria during primary
      infection. In the presence of a Th1 response, Th2 or Th17 responses do not really
      develop or play a positive or negative role during the course of B. melitensis
      infection. On the whole, these results could improve our ability to develop
      protective vaccines or therapeutic treatments against brucellosis.

PMID- 23006849
TI  - Role for telomerase in Listeria monocytogenes infection.
AB  - Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the
      human telomerase complex. Growing evidence suggests that hTERT also contributes
      to the cell physiology independently of telomere elongation. However, its role in
      bacterial infection is unknown. Here we show that hTERT is critical for Listeria
      monocytogenes infection, as the depletion of hTERT impaired bacterial
      intracellular replication. In addition, we observed that L. monocytogenes caused
      a decrease in hTERT levels at early time points of the infectious process. This
      effect was mediated by the pore-forming toxin listeriolysin O (LLO) and did not
      require bacterial entry into host cells. Calcium influx through the LLO pores
      contributed to a proteasome-independent decrease in hTERT protein levels.
      Together, our data provide evidence that these bacteria trigger hTERT
      degradation, an event that is detrimental to bacterial replication.

PMID- 23006850
TI  - FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury
      in response to Streptococcus pneumoniae: role of pneumolysin.
AB  - FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and
      differentiation factor with potential in antitumor therapies and antibacterial
      immunization strategies. However, the effect of systemic Flt3L treatment on lung
      protective immunity against bacterial infection is incompletely defined. Here, we
      examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild
      type [WT] mice), or increased Flt3L availability (in WT mice pretreated with
      Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective
      immunity against the major lung-tropic pathogen, Streptococcus pneumoniae.
      Although in Flt3L-deficient mice the numbers of DCs positive for CD11b
      (CD11b(pos) DCs) and for CD103 (CD103(pos) DCs) were diminished, lung
      permeability, a marker of injury, was unaltered in response to S. pneumoniae. In
      contrast, WT mice pretreated with Flt3L particularly responded with increased
      numbers of CD11b(pos) DCs and with less pronounced numbers of CD103(pos) DCs and
      impaired bacterial clearance and with increased lung permeability following S.
      pneumoniae challenge. Notably, infection of Flt3L-pretreated mice with S.
      pneumoniae lacking the pore-forming toxin, pneumolysin (PLY), resulted in
      substantially less lung CD11b(pos) DCs activation and reduced lung permeability.
      Collectively, this study establishes that Flt3L treatment enhances the
      accumulation of proinflammatory activated lung CD11b(pos) DCs which contribute to
      acute lung injury in response to PLY released by S. pneumoniae.

PMID- 23006851
TI  - Expression of STM4467-encoded arginine deiminase controlled by the STM4463
      regulator contributes to Salmonella enterica serovar Typhimurium virulence.
AB  - Arginine deiminase (ADI), carbamate kinase (CK), and ornithine transcarbamoylase
      (OTC) constitute the ADI system. In addition to metabolic functions, the ADI
      system has been implicated in the virulence of certain pathogens. The pathogenic
      intracellular bacterium Salmonella enterica serovar Typhimurium possesses the
      STM4467, STM4466, and STM4465 genes, which are predicted to encode ADI, CK, and
      OTC, respectively. Here we report that the STM4467 gene encodes an ADI and that
      ADI activity plays a role in the successful infection of a mammalian host by S.
      Typhimurium. An STM4467 deletion mutant was defective for replication inside
      murine macrophages and was attenuated for virulence in mice. We determined that a
      regulatory protein encoded by the STM4463 gene functions as an activator for
      STM4467 expression. The expression of the ADI pathway genes was enhanced inside
      macrophages in a process that required STM4463. Lack of STM4463 impaired the
      ability of S. Typhimurium to replicate within macrophages. A mutant defective in
      STM4467-encoded ADI displayed normal production of nitric oxide by macrophages.

PMID- 23006852
TI  - Progressive cross-reactivity in IgE responses: an explanation for the slow
      development of human immunity to schistosomiasis?
AB  - People in regions of Schistosoma mansoni endemicity slowly acquire immunity, but
      why this takes years to develop is still not clear. It has been associated with
      increases in parasite-specific IgE, induced, some investigators propose, to
      antigens exposed during the death of adult worms. These antigens include members
      of the tegumental-allergen-like protein family (TAL1 to TAL13). Previously, in a
      group of S. mansoni-infected Ugandan males, we showed that IgE responses to three
      TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age. Now,
      in a subcohort we examined associations of these responses with resistance to
      reinfection and use the data to propose a mechanism for the slow development of
      immunity. IgE was measured 9 weeks posttreatment and at reinfection at 2 years (n
      = 144). An anti-TAL5 IgE (herein referred to as TAL5 IgE) response was associated
      with reduced reinfection even after adjusting for age using regression analysis
      (geometric mean odds ratio, 0.24; P = 0.016). TAL5 IgE responders were a subset
      of TAL3 IgE responders, themselves a subset of TAL1 responders. TAL3 IgE and TAL5
      IgE were highly cross-reactive, with TAL3 the immunizing antigen and TAL5 the
      cross-reactive antigen. Transcriptional and translational studies show that TAL3
      is most abundant in adult worms and that TAL5 is most abundant in infectious
      larvae. We propose that in chronic schistosomiasis, older individuals have
      repeatedly experienced IgE antigens exposed when adult worms die (e.g., TAL3) and
      that this leads to increasing cross-reactivity with antigens of invading larvae
      (e.g., TAL5). Progressive accumulation of worm/larvae cross-reactivity could
      explain the age-dependent immunity observed in areas of endemicity.

PMID- 23006853
TI  - Virulence factors of Trypanosoma cruzi: who is who?
AB  - The aim of this review is to gather the current knowledge of Trypanosoma cruzi's
      virulence factors described to date in an integrative way, relating these with
      the parasite's life cycle and trying to elucidate their importance in each
      process. Several aspects relevant for the parasite's survival, such as invasion,
      resistance to oxidative damage, escape from the phagolysosomal vacuole and
      differentiation, among others, will be discussed. However, there is still a lot
      to learn about what virulence really means in T. cruzi and which parasite
      molecules are absolutely required to make T. cruzi one of the most successful
      pathogens to invade, survive and persist in a mammalian host.

PMID- 23006854
TI  - Hookworm virulence factors: making the most of the host.
AB  - Hookworm disease from Necator americanus and Ancylostoma duodenale affects
      approximately 700 million people, with N. americanus being the predominant
      species. Unlike other pathogens (e.g., bacterial infections), where "virulence"
      is described in regards to acute pathogenesis and case-fatality, hookworms are
      well-evolved, multicellular parasites that establish long-term infections in
      their human hosts with a subtle and chronic, but insidious, pathogenesis, usually
      in the form of iron deficiency anemia from parasite blood feeding that, over
      time, has devastating effects on the human host especially when it involves
      children or women of child bearing years. As such, many of the typical terms for
      "virulence factors" used in other reviews in this special edition cannot be
      applied to hookworm (e.g., "colonization", "invasion", "or "toxicity"); rather
      the virulence of hookworm infection comes in terms of their ability to maintain a
      chronic blood-feeding infection in the lumen of relatively healthy human hosts,
      an infection that is usually measured in years but can sometimes be measured in
      decades. In the current manuscript, we describe the routes of invasion hookworms
      take into their human hosts and the means by which they modulate the human immune
      system to maintain this long-term parasitism. Little data on hookworm infection
      comes from actual human infections; instead, much of the data is derived from
      observations of laboratory animal models, in which hookworms fail to establish
      this distinctive "chronic infection," either due to physiological or
      immunological responses of these animal models. Hence, the mode and effects of
      chronic immunity must be extrapolated from this very different sort of infection
      to humans. Herein, we aim to synthesize immunological information from both types
      of models in the context of immune regulation and protection in order to identify
      future research focuses for the development of new treatment alternatives (i.e.
      drugs and vaccines).

PMID- 23006855
TI  - Virulence factors of Toxoplasma gondii.
AB  - Toxoplasma gondii virulence is dependent on factors involved in either parasite
      host cell interaction, or in host immune response. It is essentially defined in
      the mouse and little is known concerning human infection. The genetic dependence
      of virulence is a growing field, benefiting from the recent development of
      research of the population structure of T. gondii.

PMID- 23006856
TI  - Functional recovery of human cells harbouring the mitochondrial DNA mutation
      MERRF A8344G via peptide-mediated mitochondrial delivery.
AB  - We explored the feasibility of mitochondrial therapy using the cell-penetrating
      peptide Pep-1 to transfer mitochondrial DNA (mtDNA) between cells and rescue a
      cybrid cell model of the mitochondrial disease myoclonic epilepsy with ragged-red
      fibres (MERRF) syndrome. Pep-1-conjugated wild-type mitochondria isolated from
      parent cybrid cells incorporating a mitochondria-specific tag were used as donors
      for mitochondrial delivery into MERRF cybrid cells (MitoB2) and mtDNA-depleted
      Rho-zero cells (Mitorho degrees ). Forty-eight hours later, translocation of Pep
      1-labelled mitochondria into the mitochondrial regions of MitoB2 and Mitorho
      degrees  host cells was observed (delivery efficiencies of 77.48 and 82.96%,
      respectively). These internalized mitochondria were maintained for at least 15
      days in both cell types and were accompanied by mitochondrial function recovery
      and cell survival by preventing mitochondria-dependent cell death. Mitochondrial
      homeostasis analyses showed that peptide-mediated mitochondrial delivery (PMD)
      also increased mitochondrial biogenesis in both cell types, but through distinct
      regulatory pathways involving mitochondrial dynamics. Dramatic decreases in
      mitofusin-2 (MFN2) and dynamin-related protein 1/fission 1 were observed in
      MitoB2 cells, while Mitorho degrees  cells showed a significant increase in optic
      atrophy 1 and MFN2. These findings suggest that PMD can be used as a potential
      therapeutic intervention for mitochondrial disorders.

PMID- 23006857
TI  - LibKiSAO: a Java library for Querying KiSAO.
AB  - BACKGROUND: The Kinetic Simulation Algorithm Ontology (KiSAO) supplies
      information about existing algorithms available for the simulation of Systems
      Biology models, their characteristics, parameters and inter-relationships. KiSAO
      enables the unambiguous identification of algorithms from simulation
      descriptions. Information about analogous methods having similar characteristics
      and about algorithm parameters incorporated into KiSAO is desirable for
      simulation tools. To retrieve this information programmatically an application
      programming interface (API) for KiSAO is needed. FINDINGS: We developed libKiSAO,
      a Java library to enable querying of the KiSA Ontology. It implements methods to
      retrieve information about simulation algorithms stored in KiSAO, their
      characteristics and parameters, and methods to query the algorithm hierarchy and
      search for similar algorithms providing comparable results for the same
      simulation set-up. Using libKiSAO, simulation tools can make logical inferences
      based on this knowledge and choose the most appropriate algorithm to perform a
      simulation. LibKiSAO also enables simulation tools to handle a wider range of
      simulation descriptions by determining which of the available methods are similar
      and can be used instead of the one indicated in the simulation description if
      that one is not implemented. CONCLUSIONS: LibKiSAO enables Java applications to
      easily access information about simulation algorithms, their characteristics and
      parameters stored in the OWL-encoded Kinetic Simulation Algorithm Ontology.
      LibKiSAO can be used by simulation description editors and simulation tools to
      improve reproducibility of computational simulation tasks and facilitate model re
      use.

PMID- 23006858
TI  - Chancre of the eyelid as manifestation of primary syphilis, and precocious
      chorioretinitis and uveitis in an HIV-infected patient: a case report.
AB  - BACKGROUND: Ocular syphilis is often difficult to diagnose because of the wide
      variation in clinical features.HIV co-infection may further complicate the
      picture. CASE PRESENTATION: Herein the authors report an unusual primary
      syphilitic ocular lesion in a 45-year-old Italian HIV-infected bisexual man who
      presented with a unilateral eyelid lesion. Associated precocious signs and
      symptoms in the posterior segment of both eyes, bilateral chorioretinitis and
      uveitis, are described. Intravenous penicillin and steroid treatment produced a
      rapid improvement in clinical status and complete resolution. CONCLUSIONS:
      Careful questioning about sexual behavior is crucial for unmasking unusual
      features of ocular syphilis in HIV-infected subjects.

PMID- 23006861
TI  - The dose-response relationship of balance training in physically active older
      adults.
AB  - A 6-wk group balance-training program was conducted with physically active older
      adults (based on American College of Sports Medicine requirements) to investigate
      the effect of dose-related static and dynamic balance-specific training. All
      participants, age 60-87 yr, continued their regular exercise program while adding
      balance training in 1 of 3 doses: three 20-min sessions/wk (n = 20), one 20-min
      session/wk (n = 21), or no balance training (n = 19). Static balance (single-leg
      stance, tandem), dynamic balance (alternate stepping, limits of stability), and
      balance confidence (ABC) were assessed pre- and posttraining. Significant
      interactions were observed for time in single-leg stance, excursion in limits of
      stability, and balance confidence, with the greatest increase observed in the
      group that completed 3 training sessions/wk. The results demonstrate a dose
      response relationship indicating that those who are already physically active can
      improve balance performance with the addition of balance-specific training.

PMID- 23006866
TI  - Maternal neglect with reduced depressive-like behavior and blunted c-fos
      activation in Brattleboro mothers, the role of central vasopressin.
AB  - Early mother-infant relationships exert important long-term effects in offspring
      and are disturbed by factors such as postpartum depression. We aimed to clarify
      if lack of vasopressin influences maternal behavior paralleled by the development
      of a depressive-like phenotype. We compared vasopressin-deficient Brattleboro
      mothers with heterozygous and homozygous normal ones. The following parameters
      were measured: maternal behavior (undisturbed and separation-induced); anxiety by
      the elevated plus maze; sucrose and saccharin preference and forced swim
      behavior. Underlying brain areas were examined by c-fos immunocytochemistry among
      rest and after swim-stress. In another group of rats, vasopressin 2 receptor
      agonist was used peripherally to exclude secondary changes due to diabetes
      insipidus. Results showed that vasopressin-deficient rats spend less time licking
      grooming their pups through a centrally driven mechanism. There was no difference
      between genotypes during the pup retrieval test. Vasopressin-deficient mothers
      tended to explore more the open arms of the plus maze, showed more preference for
      sucrose and saccharin and struggled more in the forced swim test, suggesting that
      they act as less depressive. Under basal conditions, vasopressin-deficient
      mothers had more c-fos expression in the medial preoptic area, shell of nucleus
      accumbens, paraventricular nucleus of the hypothalamus and amygdala, but not in
      other structures. In these areas the swim-stress-induced activation was smaller.
      In conclusion, vasopressin-deficiency resulted in maternal neglect due to a
      central effect and was protective against depressive-like behavior probably as a
      consequence of reduced activation of some stress-related brain structures. The
      conflicting behavioral data underscores the need for more sex specific studies.

PMID- 23006869
TI  - Abstracts of the 51st Annual Meeting of the European Society for Paediatric
      Endocrinology (ESPE). Leipzig, Germany. September 20-23, 2012.

PMID- 23006870
TI  - Guidelines for randomized clinical trial protocol content: a systematic review.
AB  - BACKGROUND: All randomized clinical trials (RCTs) require a protocol; however,
      numerous studies have highlighted protocol deficiencies. Reporting guidelines may
      improve the content of research reports and, if developed using robust methods,
      may increase the utility of reports to stakeholders. The objective of this study
      was to systematically identify and review RCT protocol guidelines, to assess
      their characteristics and methods of development, and to compare recommendations.
      METHODS: We conducted a systematic review of indexed literature (MEDLINE, EMBASE
      and the Cochrane Methodology Register from inception to September 2010; reference
      lists; related article features; forward citation searching) and a targeted
      search of supplementary sources, including a survey of major trial funding
      agencies in six countries. Records were eligible if they described a content
      guideline in English or French relevant to RCT protocols. Guidelines were
      excluded if they specified content for protocols for trials of specific
      procedures or conditions or were intended to assess trial quality. We extracted
      guideline characteristics and methods. Content was mapped for a subset of
      guidelines that described development methods or had institutional endorsement.
      RESULTS: Forty guidelines published in journals, books and institutional reports
      were included in the review; seven were specific to RCT protocols. Only eight
      (20%) described development methods which included informal consensus methods,
      pilot testing and formal validation; no guideline described all of these methods.
      No guideline described formal consensus methods or a systematic retrieval of
      empirical evidence to inform its development. The guidelines included a median of
      23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to
      109). Among the subset of guidelines (n = 23) for which content was mapped,
      approximately 380 concepts were explicitly addressed (median concepts per
      guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a
      minority of guidelines. CONCLUSIONS: Existing guidelines for RCT protocol content
      varied substantially in their recommendations. Few reports described the methods
      of guideline development, limiting comparisons of guideline validity. Given the
      importance of protocols to diverse stakeholders, we believe a systematically
      developed, evidence-informed guideline for clinical trial protocols is needed.

PMID- 23006871
TI  - Caring for the adult with congenital heart disease in an adult catheterization
      laboratory by pediatric interventionalists--safety and efficacy.
AB  - OBJECTIVE: The purpose of this study is to describe the outcomes of cardiac
      catheterizations performed by pediatric interventional cardiologists in an adult
      catheterization laboratory on adult patients with congenital heart disease (CHD).
      BACKGROUND: With improved survival rates, the number of adults with CHD increases
      by ~5%/year; this population often requires cardiac catheterization. METHODS:
      From January 2005 to December 2009, two groups of patients were identified, an
      adult group (>21 years) and an adolescent group (13-21 years), who had
      catheterizations performed by pediatric interventional staff. RESULTS: Fifty
      seven catheterizations were performed in 53 adults, while 59 were performed in 47
      adolescents. The male to female ratio differed significantly between groups; only
      15/53 (28%) of adults were male vs. 26/47 (55%) of adolescents (P =.006). Among
      adults, 27 had previously corrected CHD, 16 with atrial septal defect (ASD), and
      six with patent foramen ovale (PFO). This differed significantly from the
      adolescents, where only 30 had previously corrected CHD, seven with ASD, and one
      with PFO (P =.012). Among adults who were catheterized, interventions were
      performed on 28/53 (53%). All interventions were successful and included ASD/PFO
      closure, patent ductus arteriosus occlusion, coarctation dilation, pulmonary
      artery dilations, and one saphenous vein graft aneurysm closure. Nineteen adults
      had coronary angiography performed by adult interventionalists in consult with
      pediatric interventionalists. Two complications occurred among adults (3.8%) vs.
      one complication (2%; P = 1) among adolescents. No femoral vessel complications
      or catheterization-associated mortality occurred. CONCLUSIONS: Cardiac
      catheterizations can be performed effectively and safely in adults with CHD by
      pediatric interventional cardiologists in an adult catheterization laboratory.

PMID- 23006872
TI  - Percutaneous endoscopic lumbar discectomy - early clinical experience.
AB  - We report our early clinical experience with percutaneous endoscopic lumbar
      discectomy (PELD) for herniated nucleus pulposus (HNP) in the lumbar spine. We
      introduced PELD to our clinical practice in June 2009. A total of 311 patients
      with degenerative lumbar spine disease were treated in our hospital up to August
      2011. Thirty-seven patients with lumbar HNP were treated by PELD. PELD was
      carried out under local anesthesia, and the endoscope was continuously irrigated
      with saline. Twenty-eight patients were treated through the transforaminal
      approach, 5 were treated through the interlaminar approach, and 4 were treated
      through the extraforaminal approach. Surgery was discontinued due to
      uncontrollable intraoperative pain or anatomical inaccessibility in one case of
      the interlaminar approach and 2 cases of the extraforaminal approach. In the
      other 34 patients, the elapsed time of surgery was 34 to 103 minutes (mean 62.4
      minutes). Extracorporeal blood loss was insignificant. Immediate symptom relief
      was achieved in all patients, and postoperative magnetic resonance imaging
      revealed sufficient removal of the HNP. The length of the postoperative hospital
      stay was 1 or 2 days in all patients. The surgical method of PELD is completely
      different from percutaneous nucleotomy, and the aim is to directly remove the HNP
      with minimum damage to the musculoskeletal structure. Although this study is
      based on our early clinical outcomes, PELD seemed to be a promising minimally
      invasive surgery for HNP in the lumbar spine.

PMID- 23006873
TI  - Acute calcific prevertebral tendonitis mimicking tension-type headache.
AB  - A 74-year-old woman was admitted to our hospital due to severe nuchal pain and
      occipitalgia. Neurological examination found neck stiffness but no throat pain or
      dysphagia. Blood examination showed slight elevation of white blood cell count,
      but C-reactive protein level was normal. Cerebrospinal fluid examination found no
      abnormalities. Computed tomography (CT) and magnetic resonance (MR) imaging
      demonstrated no abnormalities in the brain. Cervical CT showed a small
      calcification in front of the C1 body. Cervical T(2)-weighted MR imaging showed a
      high intensity area in front of the upper cervical vertebral body from C1 to C4,
      suggesting inflammation of the longus colli muscles. We diagnosed acute calcific
      prevertebral tendonitis. She was administered nonsteroidal anti-inflammatory
      drugs. Her symptoms gradually improved and she was discharged without
      neurological deficit 8 days after admission. It is important to be aware of the
      possibility of this rare disease in a patient with severe occipitalgia but no
      sign of intracerebral lesion.

PMID- 23006874
TI  - Delayed neurological deficits induced by an epidural hematoma associated with a
      thoracic osteoporotic compression fracture.
AB  - A 79-year-old woman developed neurological deficits 6 weeks after the onset of a
      thoracic osteoporotic compression fracture. Magnetic resonance (MR) imaging of
      the thoracic spine revealed an epidural hematoma at the T10-L2 levels. Acute
      decompressive laminectomy and percutaneous vertebroplasty were performed.
      Following the surgery, the patient's neurologic deficits improved and follow-up
      MR imaging showed complete resolution of the hematoma. Spinal epidural hematomas
      are rare and associated delayed neurological deficits are extremely rare.
      Conservative treatment may be effective for epidural hematomas in neurologically
      intact patients, but epidural hematomas can be a cause of neural compression and
      symptomatic deterioration resulting in delayed neurological deficits during the
      follow-up period.

PMID- 23006875
TI  - Spinal subdural hematoma associated with traumatic intracranial interhemispheric
      subdural hematoma.
AB  - A 78-year-old female fell and hit the back of her head on the floor. Head
      computed tomography (CT) showed right acute interhemispheric subdural hematoma
      (ISDH). Her left hemiparesis worsened, so partial removal of ISDH was performed.
      The hemiparesis was improved, but leg monoparesis persisted. Lumbar magnetic
      resonance imaging showed spinal subdural hematoma (SSDH) at the S1-2 level. Nerve
      conduction velocity measurements at the knee joint to lower limb showed
      disappearance of the left peroneal nerve conduction wave, indicating that one of
      the causes of drop foot was common peroneal nerve palsy. With conservative
      therapy, her drop foot was gradually improved, then she recovered to walk with a
      stick and moved to a rehabilitation hospital. Lumbar MR imaging should be
      performed to rule out SSDH in a patient with posterior fossa subdural hematoma on
      initial head CT who develops leg palsy.

PMID- 23006876
TI  - Cerebral hemorrhage due to posterior reversible encephalopathy syndrome
      associated with autonomic dysreflexia in a spinal cord injury patient.
AB  - A 37-year-old man with C4-5 spinal cord injury (SCI) presented with abnormally
      high blood pressure after vesicocutaneous catheter exchange and was treated with
      antihypertensive agents. Two weeks later, he developed headache and visual
      disturbance, and presented with fluctuating blood pressure. Multiple subcortical
      hemorrhages in the left occipital and right frontal lobes occurred on the next
      day, and he died of increased intracranial pressure 3 weeks later. Based on the
      symptoms and computed tomography findings, the retrospective diagnosis was
      posterior reversible encephalopathy syndrome (PRES) due to autonomic dysreflexia
      (AD). AD occurs frequently in patients with quadriplegia and high paraplegia by
      distention of the bladder and bowel. PRES secondary to AD is very rare, but we
      must always be aware of this life-threatening complication in SCI patients.

PMID- 23006877
TI  - Multiple intracranial hemorrhages after cervical spinal surgery.
AB  - A 69-year-old woman presented with a rare case of multiple supra- and
      infratentorial intracranial hemorrhages after cervical laminoplasty for cervical
      spondylotic myelopathy without intraoperative liquorrhea. A wound drainage tube
      under negative pressure was placed with subsequent 380 ml of drainage in the
      first 12 hours. She had no complaint of headache and nausea at that time.
      Computed tomography of the brain obtained at 15 hours after surgery demonstrated
      cerebellar hemorrhage, acute subdural hemorrhage, subarachnoid hemorrhage,
      supratentorial intraparenchymal hemorrhage, and pneumocephalus. She was treated
      medically without consequent neurological deficits other than right hemianopsia.
      Overdrainage of cerebrospinal fluid through an occult dural tear might cause
      severely low intracranial pressure with subsequent multiple intracranial
      hemorrhages. Wound drainage should be controlled thoroughly even in patients
      without intraoperative liquorrhea.

PMID- 23006878
TI  - Bilateral supratentorial epidural hematomas: a rare complication in adolescent
      spine surgery.
AB  - A 14-year-old girl presented with a rare case of spontaneous bilateral
      supratentorial epidural hematomas which developed rapidly following cervical
      surgery. The hematomas presumably resulted from dural dynamics changes secondary
      to cerebrospinal fluid loss and intracranial hypotension. Intracranial epidural
      hemorrhage after spinal surgery is extremely uncommon with only one previous case
      report. Spontaneous intracranial epidural hematoma is an extremely rare
      complication, but should be considered as a possible complication of spine
      surgery, especially in adolescents complicated by delayed consciousness and
      breathing restoration from anesthesia. This case report expands the presently
      known clinical spectrum of this uncommon complication.

PMID- 23006879
TI  - Gas-containing disc herniations: dual nerve root compression at a single disc
      level.
AB  - A 72-year-old man presented with gas-containing disc herniations resulting in
      dual nerve root (exiting and traversing root) compression at the single level
      manifesting as lower back pain with the right anterolateral thigh and medial calf
      pain and no response to 4 weeks of conservative treatment. Physical examination
      revealed positive Lasegue's sign at 40 degrees , but the patient had no evidence
      of neurological deficit. Magnetic resonance imaging showed two separate disc
      herniations, a posterocentral herniated disc that had migrated inferiorly at the
      L3-4 level and compressed the L4 traversing root, and another that had compressed
      the L3 exiting root in the extraforaminal area at the same level. Coronal
      computed tomography demonstrated the presence of gas in the spinal canal and
      extraforaminal area at the L3-4 level, and the vacuum phenomenon was also noted
      at the L3-4 intervertebral disc. Microscopic discectomy was performed using
      midline and paramedian approaches, and the presence of gas was confirmed by
      bubbles after pouring saline into the area intraoperatively. Histological
      examination revealed fibrous tissue. The patient was discharged with complete
      relief of pain. This is a rare case of symptomatic gas-containing disc
      herniations causing dual compression of exiting and traversing roots at a single
      disc level.

PMID- 23006880
TI  - Nontraumatic cervical disc herniation in a 21-year-old patient with no other
      underlying disease.
AB  - A 21-year-old woman presented with cervical myelopathy due to nontraumatic
      cervical disc herniation associated with cervical canal stenosis. The patient
      underwent removal of the herniated disc and anterior fusion with an autogenous
      iliac crest bone graft. After surgery, the patient showed satisfactory
      improvement. Cases of cervical disc herniation in our center and reported cases
      without cervical trauma in either young adults or in childhood were reviewed
      retrospectively. We discuss the pathogenesis of cervical disc herniation in our
      young patient in the context of these other cases. Cervical disc herniation
      rarely occurs before the age of 30 years. A history of cervical trauma and
      preexisting fusion of the cervical spine are risk factors for cervical disc
      herniation. The present case is the youngest known of nontraumatic disc
      herniation without other underlying disease. Hypermobility due to neck cracking
      and a relatively narrow spinal canal might have been important in causing
      cervical myelopathy by disc herniation.

PMID- 23006881
TI  - Voluminous free disk fragment mimicking an extradural tumor.
AB  - A 56-year-old man presented with a rare case of a voluminous herniated disc
      fragment mimicking an intraspinal extradural tumor on magnetic resonance (MR)
      imaging. He had experienced low back pain and sciatica in his right leg for 12
      months, which exacerbated suddenly 4 days before admission accompanied by right
      quadriceps muscle weakness. MR imaging with gadolinium demonstrated a tumor-like
      longitudinal lesion, extending from the L1-2 to the L3-4 intervertebral disc
      spaces and occupying most of the right half of the vertebral canal. L2 and L3
      laminectomy, as well as L2-3 right foraminotomy, were performed. We were prepared
      for an oncological operation, but instead, a huge disc fragment was removed en
      bloc from the right epidural space. The patient's postoperative course was
      uneventful and he demonstrated full neurological recovery within 2 months.
      Sequestrated lumbar disc fragments must be considered in the differential
      diagnosis of longitudinal extradural mass lesions in the spinal canal
      independently of their size. MR imaging with contrast medium can differentiate
      herniated disc from tumors and other epidural lesions. Nevertheless, nontypical
      sequestrated disc herniations are extremely rare and can be misinterpreted.

PMID- 23006882
TI  - Intra-extradural dumbbell-shaped hemangioblastoma manifesting as subarachnoid
      hemorrhage in the cauda equina.
AB  - A 56-year-old man presented with a rare intra-extradural dumbbell-shaped
      hemangioblastoma in the lumbar spine associated with von Hippel-Lindau (VHL)
      disease manifesting as subarachnoid hemorrhage. The tumor, which was exiting at
      the right L2-3 intervertebral foramen, was removed successfully by total
      facetectomy and posterior spinal fusion at the L2-3 segment. Nine years later, a
      recurrent tumor due to VHL was also totally removed with minimal neurological
      complications. Accurate diagnosis of this vascular-rich lesion is essential for
      developing an adequate surgical strategy. The dumbbell-shaped tumor requires
      total facetectomy and spinal reconstruction, and care should be taken to preserve
      the entire nerve root origin by only identifying the affected nerve fascicles at
      the origin, if possible. Postoperative adhesion must be minimized for second
      surgery in patients with genetic disease such as VHL, who are likely to suffer
      recurrence.

PMID- 23006883
TI  - Rapid regrowth of a capillary hemangioma of the thoracic spinal cord.
AB  - A 48-year-old man presented with a 2-week history of progressive gait
      disturbance. Neurological examinations showed mild weakness in his lower
      extremities and depreciation of deep sensation. Magnetic resonance (MR) imaging
      showed an intradural extramedullary enhanced lesion at the levels of the T10 and
      T11 vertebrae. Laminectomy of the T10 and T11 vertebrae was performed, and the
      vascular tumor on the spinal cord surface was completely resected. Histological
      analysis indicated that the lesion was a capillary hemangioma with an elevated
      proliferative index. Postoperatively, the patient showed rapid motor and sensory
      improvement. However, 6 months after the operation, MR imaging showed regrowth of
      the tumor although the clinical symptoms of the patient had not deteriorated. The
      patient has shown no tumor regrowth 9 years after the second operation. Capillary
      hemangiomas in the skin and soft tissues are often associated with high
      proliferative activity, and recurrence/regrowth is not infrequent. On the other
      hand, recurrence/regrowth of capillary hemangioma in the neuraxis after tumor
      resection has rarely been observed, even in cases of incomplete resection. The
      present case illustrates the treatment of recurrent capillary hemangioma of the
      spinal cord.

PMID- 23006884
TI  - Favorable outcome after radical resection and subsequent local irradiation of
      malignant peripheral nerve sheath tumor in the cervical spine.
AB  - A 25-year-old man presented with malignant transformation to malignant peripheral
      nerve sheath tumor (MPNST) in the cervical spine associated with
      neurofibromatosis type 1. He presented with a 3-week history of rapidly
      increasing weakness and numbness in all four extremities. Magnetic resonance (MR)
      imaging of the cervical spine demonstrated a dumbbell-shaped tumor, which
      compressed the spinal cord at the C2-3 level. The tumor was excised, mainly
      within the spinal canal to decompress the spinal cord. The histological diagnosis
      was benign neurofibroma. Three months after surgery, he rapidly developed
      progressive tetraparesis and MR imaging revealed marked regrowth of an extradural
      mass into the spinal canal. At reoperation, the regrown mass in the spinal canal
      was totally excised. The histological diagnosis revealed MPNST. He underwent
      radiation therapy, with a total dose of 32 Gy, for approximately 3 weeks after
      the second surgery, but MR imaging showed tumor regrowth within the spinal canal,
      and his condition deteriorated. The decision was made to remove the tumor
      radically, including the involved facet and extradural lesion. Posterior fusion
      using a pedicle screw was performed one month later. He manifested no additional
      neurological deficits. He has been free of relapse for 46 months. Radical
      resection remains the most effective treatment for MPNST, although complete
      removal with a clear tumor margin is often impossible in practice.

PMID- 23006885
TI  - Radiation-induced spinal cord anaplastic astrocytoma subsequent to radiotherapy
      for testicular seminoma.
AB  - A 54-year-old man presented with a very rare case of radiation-induced
      intramedullary spinal cord anaplastic astrocytoma, which developed 37 years after
      radiotherapy for testicular seminoma. The patient presented with weakness and
      numbness of the left lower extremity that had gradually aggravated for 3 months.
      Magnetic resonance imaging demonstrated an intramedullary mass lesion with
      syringomyelia at the T9 to T12 levels. Subtotal removal of the tumor was
      performed using standard microsurgical technique. Histological examination
      revealed anaplastic astrocytoma. Although radiotherapy was seriously considered,
      chemotherapy was employed as adjuvant therapy considering the previous treatment.
      Although his neurological status improved transiently after surgery, relentless
      neurological decline occurred and resulted in death 9 months following surgery.
      Considering that subtotal removal of the tumor and chemotherapy had little
      influence on the quality of life and the length of survival in our case,
      cordectomy may be the optimum treatment for patients with radiation-induced
      spinal intramedullary malignant astrocytoma.

PMID- 23006886
TI  - Primary cauda equina lymphoma treated with high-dose methotrexate.
AB  - A 69-year-old man presented with a very rare case of primary central nervous
      system lymphoma originating in the cauda equina manifesting as progressive
      paraparesis. The patient underwent a biopsy, and was treated with intravenous
      high-dose (3.5 g/m(2)) methotrexate chemotherapy and local irradiation.
      Histological study revealed large B cell type lymphoma. Follow-up magnetic
      resonance imaging showed complete remission of the lesion, but the patient died
      of pneumonia at 18 months after the initial onset without tumor recurrence, so
      the efficacy of this strategy remains unknown.

PMID- 23006887
TI  - Acquired Chiari malformation secondary to atlantoaxial vertical subluxation in a
      patient with rheumatoid arthritis combined with atlanto-occipital assimilation.
AB  - A 65-year-old woman with a history of rheumatoid arthritis presented with a rare
      case of acquired Chiari malformation secondary to atlantoaxial vertical
      subluxation, associated with congenital atlanto-occipital assimilation.
      Syringomyelia and tetraparesis improved immediately after posterior fossa
      decompression and simultaneous occipito-cervical junction fusion. The progression
      of acquired Chiari malformation is not well known. We concluded that coexisting
      assimilation accelerated crowded foramen magnum following atlantoaxial vertical
      subluxation and induced acquired Chiari malformation over the course of a few
      years.

PMID- 23006888
TI  - Syringomyelia and arachnoid cysts associated with spinal arachnoiditis following
      subarachnoid hemorrhage.
AB  - A 66-year-old woman with primary Sjogren syndrome developed syringomyelia
      following two episodes of subarachnoid hemorrhage (SAH) due to the rupture of
      basilar artery aneurysms. Gait disturbance and abnormal sensation with pain over
      the foot and abdomen appeared 3 years after the last SAH. Magnetic resonance (MR)
      imaging revealed a syringomyelia throughout the thoracic cord, from the T2 to T11
      levels. In addition, the thoracic cord was compressed by multiple arachnoid cysts
      in the ventral side of spinal cord. Computed tomography myelography revealed
      complete block of cerebrospinal fluid (CSF) flow at the T7 level. Surgery for
      microlysis of the adhesions and restoration of the CSF flow pathway was
      performed. Postoperatively, leg motor function slowly improved and she could walk
      unaided. However, abdominal paresthesia was persisted. Postoperative MR imaging
      revealed diminished size of the syrinxes. We should recognize syringomyelia and
      arachnoid cysts due to adhesive arachnoiditis as a late complication of SAH.
      Microlysis of the adhesions focusing on the lesion thought to be the cause of the
      symptoms is one of the choices to treat massive syringomyelia and arachnoid cysts
      associated with arachnoiditis following SAH.

PMID- 23006889
TI  - New instrument for creating bone graft cavities for anterior cervical
      decompression and fusion: the anterior fusion spinal fork.
AB  - Sufficient bone decompression of osteophytes is important for positive functional
      outcomes in anterior cervical spine surgery. Achieving good alignment and bone
      fusion in anterior cervical decompression and fusion requires a bone graft bed of
      the optimum size and shape. We have developed a stainless steel instrument named
      the anterior fusion spinal fork, which is designed to aid in accurately drilling
      the bone cavity, thus enabling selection of the correct size of bone graft or
      bone graft substitutes. The device has an open design with 4 prongs, and
      resembles a three-dimensional fork. This instrument assists in guiding the
      direction of drilling, and marking the drilling point of the graft cavity with
      pyoctanin markers. We have used this instrument in 40 cases of anterior cervical
      spine surgery using the modified Smith-Robinson procedure since March 2000. This
      simple instrument allowed us to design and construct a bone graft cavity of the
      correct size and shape for iliac bone graft or bone graft substitutes for
      anterior cervical spine surgery.

PMID- 23006891
TI  - Remitting seronegative symmetrical synovitis with pitting edema syndrome caused
      by crystal-induced arthritis of the wrist: a case report.
AB  - OBJECTIVE: To describe a rare case of remitting seronegative symmetrical
      synovitis with pitting edema (RS3PE) syndrome caused by gouty arthritis. CLINICAL
      PRESENTATION AND INTERVENTION: A 76-year-old man presented with swelling and pain
      in the dorsum of feet and hands bilaterally. From the laboratory and radiologic
      findings, the diagnosis of gout-induced RS3PE syndrome was made. Conservative
      therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular
      corticosteroid injection in the wrist joint completely and rapidly resolved all
      symptoms. The patient was successfully treated with oral administration of NSAIDs
      and a one-time intra-articular corticosteroid injection in the left wrist joint.
      CONCLUSION: This case demonstrated the importance of considering the possibility
      of crystal-induced arthritis such as gout and pseudogout, as well as malignant
      disease, when diagnosing the primary disease responsible for RS3PE syndrome.

PMID- 23006890
TI  - Regulation of tissue factor coagulant activity on cell surfaces.
AB  - Tissue factor (TF) is a transmembrane glycoprotein and an essential component of
      the factor VIIa-TF enzymatic complex that triggers activation of the coagulation
      cascade. Formation of TF-FVIIa complexes on cell surfaces not only trigger the
      coagulation cascade but also transduce cell signaling via activation of protease
      activated receptors. Tissue factor is expressed constitutively on cell surfaces
      of a variety of extravascular cell types, including fibroblasts and pericytes in
      and surrounding blood vessel walls and epithelial cells, but is generally absent
      on cells that come into contact with blood directly. However, TF expression could
      be induced in some blood cells, such as monocytes and endothelial cells,
      following an injury or pathological stimuli. Tissue factor is essential for
      hemostasis, but aberrant expression of TF leads to thrombosis. Therefore, a
      proper regulation of TF activity is critical for the maintenance of hemostatic
      balance and health in general. TF-FVIIa coagulant activity at the cell surface is
      influenced not only by TF protein expression levels but also independently by a
      variety of mechanisms, including alterations in membrane phospholipid composition
      and cholesterol content, thiol-dependent modifications of TF allosteric disulfide
      bonds, and other post-translational modifications of TF. In this article, we
      critically review the key literature on mechanisms by which TF coagulant activity
      is regulated at the cell surface in the absence of changes in TF protein levels
      with specific emphasis on recently published data and provide the authors'
      perspective on the subject.

PMID- 23006892
TI  - Pifithrin-MU increases mitochondrial COX biogenesis and MnSOD activity in
      skeletal muscle of middle-aged mice.
AB  - We investigated the biogenesis and mitochondrial antioxidant capacity of
      cytochrome c oxidase (COX) within the skeletal muscle under the treatments of p53
      inhibitors (pifithrin, PFTalpha and PFTMU). Significantly, PFTMU increased mtDNA
      content and COX biogenesis. These changes coincided with increases in the
      activity and expression of manganese superoxide dismutase (MnSOD), the key
      antioxidant enzyme in mitochondria. Conversely, PFTalpha caused muscle loss,
      increased oxidative damage and decreased MnSOD activity in intermyofibrillar
      (IMF) mitochondria. Mechanically, PFTMU inhibited p53 translocation to
      mitochondria and thus increased its transcriptional activity for expression of
      synthesis of cytochrome c oxidase 2 (SCO2), an important assembly protein for
      COX. This study provides in vivo evidence that PFTMU, superior to PFTalpha,
      preserves muscle mass and increases mitochondrial antioxidant activity.

PMID- 23006893
TI  - Advances in genome-wide RNAi cellular screens: a case study using the Drosophila
      JAK/STAT pathway.
AB  - BACKGROUND: Genome-scale RNA-interference (RNAi) screens are becoming ever more
      common gene discovery tools. However, whilst every screen identifies interacting
      genes, less attention has been given to how factors such as library design and
      post-screening bioinformatics may be effecting the data generated. RESULTS: Here
      we present a new genome-wide RNAi screen of the Drosophila JAK/STAT signalling
      pathway undertaken in the Sheffield RNAi Screening Facility (SRSF). This screen
      was carried out using a second-generation, computationally optimised dsRNA
      library and analysed using current methods and bioinformatic tools. To examine
      advances in RNAi screening technology, we compare this screen to a biologically
      very similar screen undertaken in 2005 with a first-generation library. Both
      screens used the same cell line, reporters and experimental design, with the SRSF
      screen identifying 42 putative regulators of JAK/STAT signalling, 22 of which
      verified in a secondary screen and 16 verified with an independent probe design.
      Following reanalysis of the original screen data, comparisons of the two gene
      lists allows us to make estimates of false discovery rates in the SRSF data and
      to conduct an assessment of off-target effects (OTEs) associated with both
      libraries. We discuss the differences and similarities between the resulting data
      sets and examine the relative improvements in gene discovery protocols.
      CONCLUSIONS: Our work represents one of the first direct comparisons between
      first- and second-generation libraries and shows that modern library designs
      together with methodological advances have had a significant influence on genome
      scale RNAi screens.

PMID- 23006895
TI  - Elevated plasma homocysteine level is not primarily related to Alzheimer's
      disease.
AB  - BACKGROUND: A moderate elevation of plasma total homocysteine (tHcy) is
      considered a potential risk factor for Alzheimer's disease (AD). METHODS: We have
      investigated the main determinants (age, renal impairment, cobalamin/folate
      status and the presence of vascular disease) of plasma tHcy in 326 patients with
      AD, and also in 281 patients with mild cognitive impairment (MCI), since about
      half of these patients develop AD during the first 5 years. RESULTS: Elevated
      plasma tHcy in patients with AD could mainly be attributed to cobalamin/folate
      deficiency or renal impairment. Younger patients (below 75 years) with AD and
      patients with MCI without cobalamin/folate deficiency or renal impairment showed
      normal levels of plasma tHcy. CONCLUSION: Our findings suggest that plasma tHcy
      is not primarily involved in the pathogenesis of AD but rather a reflection of
      changes of the main determinants of plasma tHcy in AD patients.

PMID- 23006894
TI  - Reduced basal ganglia MU-opioid receptor availability in trigeminal neuropathic
      pain: a pilot study.
AB  - BACKGROUND: Although neuroimaging techniques have provided insights into the
      function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in
      humans, there is little understanding of the molecular mechanisms affected during
      the course of this disorder. Understanding these processes is crucial to
      determine the systems involved in the development and persistence of TNP.
      FINDINGS: In this study, we examined the regional MU-opioid receptor (MUOR)
      availability in vivo (non-displaceable binding potential BPND) of TNP patients
      with positron emission tomography (PET) using the MUOR selective radioligand
      [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy
      controls were examined with PET. Patients with TNP showed reduced MUOR BPND in
      the left nucleus accumbens (NAc), an area known to be involved in pain modulation
      and reward/aversive behaviors. In addition, the MUOR BPND in the NAc was
      negatively correlated with the McGill sensory and total pain ratings in the TNP
      patients. CONCLUSIONS: Our findings give preliminary evidence that the clinical
      pain in TNP patients can be related to alterations in the endogenous MU-opioid
      system, rather than only to the peripheral pathology. The decreased availability
      of MUORs found in TNP patients, and its inverse relationship to clinical pain
      levels, provide insights into the central mechanisms related to this condition.
      The results also expand our understanding about the impact of chronic pain on the
      limbic system.

PMID- 23006896
TI  - Real-time spectrum estimation-based dual-channel speech-enhancement algorithm for
      cochlear implant.
AB  - BACKGROUND: Improvement of the cochlear implant (CI) front-end signal acquisition
      is needed to increase speech recognition in noisy environments. To suppress the
      directional noise, we introduce a speech-enhancement algorithm based on
      microphone array beamforming and spectral estimation. The experimental results
      indicate that this method is robust to directional mobile noise and strongly
      enhances the desired speech, thereby improving the performance of CI devices in a
      noisy environment. METHODS: The spectrum estimation and the array beamforming
      methods were combined to suppress the ambient noise. The directivity coefficient
      was estimated in the noise-only intervals, and was updated to fit for the mobile
      noise. RESULTS: The proposed algorithm was realized in the CI speech strategy.
      For actual parameters, we use Maxflat filter to obtain fractional sampling points
      and cepstrum method to differentiate the desired speech frame and the noise
      frame. The broadband adjustment coefficients were added to compensate the energy
      loss in the low frequency band. DISCUSSIONS: The approximation of the directivity
      coefficient is tested and the errors are discussed. We also analyze the algorithm
      constraint for noise estimation and distortion in CI processing. The performance
      of the proposed algorithm is analyzed and further be compared with other
      prevalent methods. CONCLUSIONS: The hardware platform was constructed for the
      experiments. The speech-enhancement results showed that our algorithm can
      suppresses the non-stationary noise with high SNR. Excellent performance of the
      proposed algorithm was obtained in the speech enhancement experiments and mobile
      testing. And signal distortion results indicate that this algorithm is robust
      with high SNR improvement and low speech distortion.

PMID- 23006897
TI  - Hemodynamic interactions in the eye: a review.
AB  - The ocular circulation provides readily visible information about the state of
      the systemic circulation, as well as being potentially of relevance to the
      pathogenesis of ocular disorders such as glaucoma. The interaction between
      intraocular pressure, retinal vessels and cerebrospinal fluid pressure located at
      the retrolaminar portion of the eye has been of great interest for both
      ophthalmic and neurological clinicians and researchers. Understanding the
      relationship between these physiological parameters can explain phenomena such as
      spontaneous retinal venous pulsatility, and characterize the effects of the
      translaminar pressure gradient. It may be feasible to use measurable changes in
      venous pulsatility to enhance clinical assessment in different diseases. In this
      article we review recent findings on ocular hemodynamics and the relevance of
      these parameters in the diagnosis of ophthalmic and neurological diseases.

PMID- 23006898
TI  - Glucocorticoid-endocannabinoid interaction in cardiac surgical patients:
      relationship to early cognitive dysfunction and late depression.
AB  - BACKGROUND: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid
      signaling molecules that are important for adaptation to stressful and aversive
      situations.They are known to interact with glucocorticoids and other stress
      responsive systems. Maladaptation to acute or chronic stress represents a major
      risk factor for the development of psychiatric disorders. In the present study,
      we administered stress doses of hydrocortisone ina prospective, randomized,
      placebo-controlled double blind study in patients undergoing cardiac surgery (CS)
      to examine the relationship between the use of glucocorticoids, plasma EC levels,
      and the occurrence of early postoperative cognitive dysfunction (delirium) and of
      later development of depression. METHODS: We determined plasma levels of the ECs
      anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone
      (n=56) and the placebo group(n=55) preoperatively, at postoperative day (POD) 1,
      at intensive care unit discharge, and at 6 months after CS(n=68). Postoperative
      delirium was diagnosed according to Diagnostic and Statistical Manual of the
      American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression
      was determined by validated questionnaires and a standardized psychological
      interview (Structured Clinical Interview for DSM-IV). RESULTS: Stress doses of
      hydrocortisone did not affect plasma EC levels and the occurrence of delirium or
      depression. However, patients who developed deliriumon POD 1 had significantly
      lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8
      vs. 11.3ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of
      postoperative delirium (sensitivity=0.70;specificity=0.69; cutoff value=4.9
      ng/ml; receiver operating characteristic curve area=0.70; 95 o/o confidence
      interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had
      significantly lower anandamide and 2-AG levels during the perioperative period.
      CONCLUSIONS: A low perioperative EC response may indicate an increased risk for
      early cognitive dysfunction and long-term depression in patients after CS.
      Glucocorticoids do not seem to influence this relationship.

PMID- 23006899
TI  - Modeling specific phobias and posttraumatic stress disorder in rodents: the
      challenge to convey both cognitive and emotional features.
AB  - Aberrant emotional memory processing is a core, disabling feature of both
      specific phobias and posttraumatic stress disorder (PTSD), two psychiatric
      diseases of significant prevalence and morbidity whose cognitive symptoms cannot
      be adequately treated by current psychopharmacological tools. Elucidating the
      neurobiological mechanisms involved in the etiology of these diseases is of great
      interest for the identification of new therapeutics that improve not only the
      symptomatology but also the full recovery from the pathology. To this aim,
      several animal models have been proposed based on substantial resemblance between
      the behavioral alterations seen in animals and the human pathology. The purpose
      of this review is to describe and comment on the most commonly used rodent models
      of specific phobias and PTSD. A particular focus will be reserved to the cued
      version of fear conditioning, as the highly specific stimulus-bound conditioned
      fear response seems to fit well with clinical descriptions of phobic
      fear.Moreover, animal models of PTSD will be evaluated by referring to three
      elements that are considered essential ina valid model of this disease: stressor
      exposure, memory for the stressor, and anxiety-related behaviors. Finally,
      current therapeutic directions, with a focus on cannabinoid and glucocorticoid
      compounds, will be briefly outlined.

PMID- 23006900
TI  - Determination of the fatty acid profile of neutral lipids, free fatty acids and
      phospholipids in human plasma.
AB  - BACKGROUND: Knowledge of the fatty acid composition of lipid classes in human
      plasma is an important factor in the investigation of human metabolism.
      Therefore, a method for the analysis of neutral lipid (NL), phospholipid (PL) and
      free fatty acids (FFA) in human plasma has been developed and validated. METHODS:
      Separation of lipid classes was carried out by solid phase extraction of the
      lipid extract. The fractions were transesterified and the resulting fatty acid
      methyl esters were determined by GC/FID. For the method to be validated,
      precision, detection and quantification limits, as well as recovery, were
      determined for combined lipid extraction, solid phase extraction and GC analysis.
      RESULTS: The lipid extraction was miniaturized and simplified by application of
      an ultrasound 'Sonotrode'. The resolution of lipid classes was optimized with
      appropriate standards added to a representative plasma sample. In addition, a
      rapid derivatization procedure using trimethylsulfoniumhydroxide was established.
      Low determination limits (1.5, 0.2 and 1.3 MUg/g plasma for NL, PL and FFA,
      respectively) indicate that the method's sensitivity is sufficient to quantify
      even minor components. Furthermore, recovery for NL and PL fatty acids was found
      to range from 80% to 110%. The results were similar for FFA apart from more polar
      free fatty acids due to their higher solubility in water. Repetitive measurements
      showed very good precision apart from the long chain PUFA for which the
      coefficients of variation were significantly higher. CONCLUSIONS: The present
      method is applicable to the quantitation of fatty acids in lipid classes of human
      plasma including several minor components.

PMID- 23006901
TI  - CA125 reference values change in male and postmenopausal female subjects.
AB  - BACKGROUND: In cancer patients, including women with a diagnosis of ovarian
      cancer, cancer antigen 125 (CA125) is used to evaluate the presence of peritoneal
      involvement. The aims of the present study were to assess CA125 reference
      intervals and reference change values (RCV) in postmenopausal reference women,
      postmenopausal women breast cancer free, reference men and cancer free men.
      METHODS: The series consisted of 433 subjects: 105 postmenopausal breast cancer
      free women and 56 cancer free men in addition to a total of 272 reference
      subjects (145 postmenopausal women and 127 men). Repeated CA125 measurements were
      made in a subset of 149 women and 54 men to calculate RCV and index of
      individuality. Serum CA125 levels were evaluated by a chemiluminescent assay.
      RESULTS: In postmenopausal reference women, the mean CA125 value and 2.5th-97.5th
      percentiles were 6.70, 2.60-11.00 kU/L, respectively, with a unidirectional RCV
      of 38.4%. In postmenopausal breast cancer free women, the mean CA125 value and
      2.5th-97.5th percentile were 7.45, 4.09-10.92 kU/L, respectively, with a RCV of
      34.5%. The difference between the means was statistically significant (t=-3.02,
      p=0.003). In the two male subgroups, the difference between the means for CA125
      was not statistically significant (t=0.43, p=0.665). On considering the entire
      male population, the mean CA125 value and 2.5th-97.5th percentiles were 7.50 and
      2.40-13.2 kU/L, respectively, while the unidirectional RCV was 34.3%. In all the
      studied groups, the indices of individuality were equal to or below 0.6.
      CONCLUSIONS: The extremely low index of individuality found underlines the
      importance of using the RCV instead of absolute values as a parameter when
      interpreting the CA125 data in the monitoring and follow-up of patients with
      ovarian cancer.

PMID- 23006902
TI  - Development of a rapid, simple assay of plasma total carotenoids.
AB  - BACKGROUND: Plasma total carotenoids can be used as an indicator of risk of
      chronic disease. Laboratory analysis of individual carotenoids by high
      performance liquid chromatography (HPLC) is time consuming, expensive, and not
      amenable to use beyond a research laboratory. The aim of this research is to
      establish a rapid, simple, and inexpensive spectrophotometric assay of plasma
      total carotenoids that has a very strong correlation with HPLC carotenoid profile
      analysis. RESULTS: Plasma total carotenoids from 29 volunteers ranged in
      concentration from 1.2 to 7.4 MUM, as analyzed by HPLC. A linear correlation was
      found between the absorbance at 448 nm of an alcohol / heptane extract of the
      plasma and plasma total carotenoids analyzed by HPLC, with a Pearson correlation
      coefficient of 0.989. The average coefficient of variation for the
      spectrophotometric assay was 6.5% for the plasma samples. The limit of detection
      was about 0.3 MUM and was linear up to about 34 MUM without dilution.
      Correlations between the integrals of the absorption spectra in the range of
      carotenoid absorption and total plasma carotenoid concentration gave similar
      results to the absorbance correlation. Spectrophotometric assay results also
      agreed with the calculated expected absorbance based on published extinction
      coefficients for the individual carotenoids, with a Pearson correlation
      coefficient of 0.988. CONCLUSION: The spectrophotometric assay of total
      carotenoids strongly correlated with HPLC analysis of carotenoids of the same
      plasma samples and expected absorbance values based on extinction coefficients.
      This rapid, simple, inexpensive assay, when coupled with the carotenoid health
      index, may be useful for nutrition intervention studies, population cohort
      studies, and public health interventions.

PMID- 23006903
TI  - Significant association between renal function and amyloid-positive area in renal
      biopsy specimens in AL amyloidosis.
AB  - BACKGROUND: The kidney is a major target organ for systemic amyloidosis that
      often affects the kidney including proteinura, and elevated serum creatinine
      (Cr). The correlation between amount of amyloid deposits and clinical parameters
      is not known. The aim of this study was to clarify correlation the amyloid area
      in all renal biopsy specimen and clinical parameters. METHODS: Fifty-eight
      patients with an established diagnosis of AL amyloidosis participated in the
      study. All patients showed amyloid deposits in renal biopsies. We retrospectively
      investigated the correlation between clinical data and amyloid occupied area in
      whole renal biopsy specimens. RESULTS: The area occupied by amyloid was less than
      10% in 57 of the 58 patients, and was under 2% in 40. For statistical analyses,
      %amyloid-positive areas were transformed to common logarithmic values
      (Log10%amyloid). Cr showed significant correlation with Log10%amyloid and
      estimated glomerular filtration rate (eGFR) showed the significant negative
      correlation. Patient age, cleatinine clearance (Ccr), blood urea nitorogen, and
      urinary protein was not significantly correlated with Log10%amyloid. The
      correlation with other clinical factors such as sex, and serum concentrations of
      total protein, albumin, immunoglobulins, compliments was evaluated. None of these
      factors significantly correlated with Log10%amyloid. According to sex- and age-
      adjusted multiple linear regression analysis, Log10%amyloid had significant
      positive association with Cr and significant negative association with eGFR.
      CONCLUSION: There is significant association between amyloid-positive area in
      renal tissue and renal function, especially Cr and eGFR. The level of Cr and eGFR
      may be a marker of amount of amyloid in renal tissue.

PMID- 23006904
TI  - A natural antiviral and immunomodulatory compound with antiangiogenic properties.
AB  - Meliacine (MA), an antiviral principle present in partially purified leaf
      extracts of Melia azedarach L., reduces viral load and abolishes the inflammatory
      reaction and neovascularization during the development of herpetic stromal
      keratitis in mice. 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA,
      displays anti-herpetic and immunomodulatory activities in vitro. We investigated
      whether CDM interferes with the angiogenic process. CDM impeded VEGF
      transcription in LPS-stimulated and HSV-1-infected cells. It proved to have
      neither cytotoxic nor antiproliferative effect in HUVEC and to restrain HUVEC
      migration and formation of capillary-like tubes. Moreover, MA inhibits LMM3 tumor
      induced neovascularization in vivo. We postulate that the antiangiogenic activity
      of CDM displayed in vitro as a consequence of their immunomodulatory properties
      is responsible for the antiangiogenic activity of MA in vivo, which would be
      associated with the lack of neovascularization in murine HSV-1-induced ocular
      disease.

PMID- 23006905
TI  - Intranuclear localization of apoptosis-inducing factor and endonuclease G
      involves in peroxynitrite-induced apoptosis of spiral ganglion neurons.
AB  - OBJECTIVES: The present study was designed to determine whether or not the
      caspase-independent apoptotic pathway participated in the cellular death of
      spiral ganglion neurons (SGNs) after exposure to peroxynitrite (ONOO(-)), with
      particular attention given to the  intranuclear translocation of mitochondrial
      apoptosis-inducing factor (AIF) and endonuclease G (Endo G) in this process.
      METHODS: The rat SGNs were isolated and primary cultured in vitro and were
      exposed to ONOO(-) with pre-treatment of pan-caspase inhibitor.  Morphological
      changes of SGNs were observed by acridine orange cytochemistry staining, and
      apoptosis was examined by flow cytometry. The translocation of mitochondrial AIF
      and Endo G was detected by immunocytochemistry and Western blot. The protein
      expressions of Bcl-2 family in SGNs exposed  to ONOO(-) were determined by
      Western blot. RESULTS: Treatment of SGNs with ONOO(-) resulted in the occurrence
      of caspase-independent apoptosis as evidenced by acridine orange staining and
      flow cytometry analysis. The immunocytochemical analysis showed  that AIF and
      Endo G labeling were marked in neuronal nuclei, while the Western blot
      demonstrated the intranuclear localization of AIF and Endo G in SGNs treated with
      ONOO(-). Western blot analysis demonstrated that ONOO(-) increased the Bax
      expression while reducing  Bcl-2 expression, which was not prevented by pre
      treatment with caspase inhibitor. CONCLUSION: These data indicate that ONOO(-)
      can trigger caspase-independent apoptosis in SGNs associated with mitochondrial
      AIF and Endo G intranuclear localization.

PMID- 23006906
TI  - Small hepatocellular carcinomas and thrombocytopenia.
AB  - BACKGROUND: Clinical phenotypes of small and large hepatocellular carcinomas
      (HCCs) are not well characterized. AIM: To evaluate the characteristics of small
      HCCs diagnosed by screening. METHOD: A cohort of 430 small HCCs that were
      diagnosed through screening, were dichotomized according to a size of <= 3 cm or
      >3 cm maximum tumor diameter and compared for radiological and blood-test
      parameters. RESULTS: There were 330 males and 100 females. A higher percent of
      females had smaller tumors. The majority of patients had single tumors, but 15%
      of those with larger tumors had portal vein thrombosis (PVT) compared to 5% of
      those with smaller tumors. Significant differences between the tumor-size groups
      included alpha-fetoprotein (AFP) values and platelet counts, with
      thrombocytopenia and elevated bilirubin levels being associated with smaller
      tumors. In comparing PVT-positive and PVT-negative patients, AFP levels and
      platelet counts were also significantly different between the 2 groups. A mean
      multinomial multiple logistic regression model was developed for maximum tumor
      diameter plus PVT. CONCLUSIONS: The finding of larger tumors being associated
      with normal platelets and bilirubin levels in comparison to smaller tumors having
      thrombocytopenia reveals 2 different patterns of HCC presentation.

PMID- 23006907
TI  - A sensitive method for rapid detection of alkyl halides and dehalogenase activity
      using a multistep enzyme assay.
AB  - A method for the detection of haloalkane conversion to the corresponding
      alcohols by haloalkane dehalogenases is described. It is based on a multistage
      enzyme reaction which allows for the analysis of alkyl halides in buffered
      systems. Irreversible hydrolytic dehalogenation catalyzed by haloalkane
      dehalogenase DhaA from Rhodococcus erythropolis transfers an alkyl halide into a
      corresponding alcohol that is further oxidized by alcohol oxidase AOX from Pichia
      pastoris yielding a respective aldehyde and hydrogen peroxide easily detectable
      via the horseradish peroxidase catalyzed oxidation of chromogenic molecules. Due
      to its high sensitivity (0.025 mM, 0.43 ppm for 1,3-dibromopropane), low
      expenditure and the ability of handling a large number of samples in parallel,
      this method is an attractive alternative to existing procedures for the
      monitoring of both haloalkanes and dehalogenases.

PMID- 23006908
TI  - Ethnicity and waterpipe smoking among US students.
AB  - OBJECTIVES: To examine the effect of ethnicity on waterpipe smoking among college
      students. DESIGN: A cross-sectional study utilized data from University of
      Houston students through an online survey (n = 2334) from March to April 2011.
      The survey included questions on demographic  characteristics (sex, age,
      race/ethnicity), tobacco use experience, risk perception, social acceptability
      and popularity. Multivariate logistic regression was used to determine predictors
      of waterpipe use with three outcomes: ever-use vs. no use, past-year use vs. no
      use and past-month use  vs. no use. RESULTS: Half of the sample had previously
      smoked tobacco using a waterpipe, approximately a third in the past year and
      12.5% in the past month. Significant predictors included Middle Eastern
      ethnicity, Middle Eastern friend, past cigarette or cigar use. Perception of harm
      was  associated with less use in the ever-use model, while perceived
      addictiveness, social acceptability and popularity of waterpipes were predictors
      in all models. CONCLUSION: Our findings underscore the importance of developing
      culturally appropriate interventions to control waterpipe smoking  among Middle
      Eastern Americans and those of Indian/Pakistani descent to curb further spread in
      US society, and highlight the importance of developing interventions that target
      the perceived addictiveness, social acceptability and popularity of waterpipe
      smoking.

PMID- 23006909
TI  - Carbon nanotube-based antimicrobial biomaterials formed via layer-by-layer
      assembly with polypeptides.
AB  - Biomaterials capable of suppressing microbial infection are of clear importance
      in various health care applications, e.g. implantable devices. In this study, we
      investigate the antimicrobial activity of single-walled carbon nanotubes (SWNT)
      layer-by-layer (LbL) assembled with the polyelectrolytes poly(L-lysine) (PLL) and
      poly(L-glutamic acid) (PGA). SWNT dispersion in aqueous solution is achieved
      through the biocompatible nonionic surfactant polyoxyethylene(20) sorbitan
      monolaurate (Tween 20), and the amphiphilic polymer phospholipid-poly(ethylene
      glycol) (PL-PEG). Absorbance spectroscopy and transmission electron microscopy
      (TEM) show SWNT with either Tween 20 or PL-PEG in aqueous solution to be well
      dispersed, at about the level of SWNT in chloroform. Quartz crystal
      microgravimetry with dissipation (QCMD) measurements show both SWNT-Tween and
      SWNT-PL-PEG to LbL assemble with PLL and PGA into multilayer films, with the PL
      PEG system yielding the greater final SWNT content. Escherichia coli and
      Staphylococcus epidermidis inactivation rates are significantly higher (up to
      90%) upon 24h incubation with SWNT containing films, compared to control films
      (ca. 20%). This study demonstrates the potential usefulness of SWNT/PLL/PGA thin
      films as antimicrobial biomaterials.

PMID- 23006910
TI  - Knowledge and use of Transcutaneous Electrical Stimulation (TENS) among Nigerian
      physical therapists.
AB  - AIMS AND OBJECTIVE: The purpose of this study was to evaluate the knowledge and
      the use of Transcutaneous Electrical Nerve Stimulation (TENS) by Nigerian
      physical therapists. METHODS: A cross sectional study design was carried out
      among Nigerian physical therapists. Eighty-six physical therapists participated
      in this study and data were collected using a structured and validated
      questionnaire. Copies of the questionnaires were distributed by hand and by mail
      (with self addressed envelopes) to various hospitals, clinics, universities that
      offer physical therapy services/programmes across Nigeria. Data were analyzed
      using descriptive statistics. RESULTS: Academic staff constituted 10.5% while
      89.5% were clinicians. First degree holders constituted 61.6% while 38.4% had
      postgraduate degrees. Majority of physical therapists, 90.7% use TENS, 83% of
      those who use TENS are aware of the different types of TENS; 98.72% use TENS for
      30 minutes or less, 48.7% use it for 15 minutes or less. The frequency commonly
      use is between 1-30 Hz and about 12.8% of those using this frequency believed
      that TENS relieves pain through the pre-synaptic inhibition, endogenous pain
      control, and direct inhibition of abnormally excited nerve and restoration of
      afferent input. Furthermore, 12.8% calibrated their TENS devices. Only 6.4% have
      published TENS related papers in the last five years while 29.5% have attended
      TENS related seminar in the past. Majority, 88.5% considered TENS to be cost
      effective. CONCLUSION: This study concluded that TENS is widely used among
      Nigerian physical therapists and tend to have adequate knowledge of TENS and its
      application in the management of pain.

PMID- 23006911
TI  - Observation of the expansion behavior and quantitative evaluation of elastic
      recoil of a balloon-expandable stent in three dimensions using a Micro-CT system.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) with stent implantation is
      widely used for the treatment of coronary stenosis. However, restenosis after
      stent implantation frequently reported by intravascular ultrasound evaluation.
      This may occur because of the reduced luminal area after implantation,
      insufficient stent expansion, or by the elastic recoil of the stent (ERS).
      Quantitative evaluation of stent expanding should provide further information on
      how to decrease the incidence of re-stenosis. Many previous studies have observed
      stent properties in 2D. However, the stent geometry is changed in 3D space, and
      3D measurements will provide further information on factors such as the risk for
      asymmetric ERS. We performed 3D reconstruction using high spatial resolution
      images obtained with a Micro-CT system to observe the 3D expansion behavior of a
      test stent and quantitatively evaluate ERS. The expansion behavior of each
      structural component of the stent varied, as did the ERS and eccentricity. ERS
      ranged from 2.4% to 9.2% during observation form proximal and distal positions in
      each component. The greatest difference in ERS between 2D and 3D measurements was
      5.2%. 3D measurements provide more information on ERS than 2D measurements. Our
      result shows the importance of the observation, and the evaluation by three
      dimensions.

PMID- 23006912
TI  - Development of a WLAN-based real time localization system for patient tracking in
      a Level I Trauma center.
AB  - BACKGROUND: Patient tracking helps improve workflow, decrease wait times,
      optimize costs, and enhance medical treatment in the outpatient setting. In that
      regard, real-time patient tracking may serve as a potential way to perform
      efficient patient care. In recent years, the increasing popularity of wireless
      local area networks (WLANs) has led to a growing number of devices utilizing
      wireless fidelity (WiFi) networks. This application has been used in various
      industries to enhance management processes. In that regard, we believe that this
      technology may enhance patient tracking, as the existing WLAN architecture in
      many clinics may allow for real-time tracking of patients. However, current
      literature regarding the clinical applicability of these devices is sparse. The
      aim of this study is to analyze the developmental process and feasibility of our
      protytope model for real-time patient tracking, using WLAN in the outpatient
      setting of our Level I Trauma center. METHODS: We performed the study in various
      stages. First, we analyzed our current patient workflow, and then devised a study
      protocol and prototype model that implemented both this workflow schematic and
      our current technology infrastructure. Second, we implemented our prototype model
      to determine the accuracy, feasibility, and safety of data transmission in our
      clinical setting. The factors examined during prototype implementation included
      the accuracy of patient localization and the time spent by each patient in the
      various areas of our clinic (as determined by patient tracking). RESULTS: In our
      outpatient clinic, our prototype was capable of localizing and automating patient
      data with excellent accuracy and security. CONCLUSIONS: WLAN-based real-time
      patient localization systems can help overcome a number of common challenges and
      inefficiencies seen in the outpatient clinics. Real-time localization systems
      using WLAN technology performed adequately and safely in this pilot study. We
      believe that this will eventually lead to lower costs overall due to the
      improvements in efficiency. While the initial investment costs may be high,
      implemeting this system in a pre-existing WLAN and WiFi infrastructure should
      help minimize the start-up costs.

PMID- 23006913
TI  - In situ tele-thermographic measurements during PMMA spacer augmentation in
      temporary arthrodesis after periprosthetic knee joint infection.
AB  - Poly-Methylmethacrylate (PMMA) is widely-used in orthopaedic surgery in revision
      arthroplasty or as a spacer in temporary arthrodesis of periprostehtic knee joint
      infection during a two stage procedure. The intra-operative temperature
      behaviour, however, has not yet been quantified. It is known that high
      temperature induce thermally necrosis of surrounding bone tissue during
      polymerisation process. The aim was to evaluate the PMMA surface temperature
      during polymerisation phase in situ. We hypothesized, that temperature measured
      in vivo could become critical in terms of the induction of thermal bone necrosis
      during the polymerisation phase of PMMA. The PMMA surface was measured tele
      thermographically in situ during knee arthroplasty revision surgery. Infrared
      pictures were analyzed for temperature peaks and changes. Measurements yielded
      maximum PMMA-surface-temperatures ranging from 101 to 110 degrees and a two
      minute-plateau of > 100 degrees . Hot PMMA during the polymerisation phase could
      potentially induce tissue (bone) necrosis. Therefore temperature of PMMA of more
      than 70 degrees should be avoided. Cooling of the PMMA is highly recommendable.

PMID- 23006914
TI  - Vitamin A deficiency in nineteenth century naval medicine.

PMID- 23006915
TI  - Paris in the time of Francois Magendie.

PMID- 23006916
TI  - Deprivation provides a laboratory.

PMID- 23006917
TI  - Free but not equal.

PMID- 23006918
TI  - The long, rocky road to understanding vitamins.

PMID- 23006919
TI  - Milk, butter, and early steps in human trials.

PMID- 23006920
TI  - Rise of the 'anti-infective vitamin'.

PMID- 23006921
TI  - Vitamin A deficiency in Europe's former colonies.

PMID- 23006922
TI  - Saving the children: rescue missions against strong undertow.

PMID- 23006923
TI  - Night blindness among black troops and white troops in the US Civil War.

PMID- 23006926
TI  - The vitamin A story--lifting the shadow of death. Preface.

PMID- 23006928
TI  - Cardio-respiratory outcomes associated with exposure to wildfire smoke are
      modified by measures of community health.
AB  - BACKGROUND: Characterizing factors which determine susceptibility to air
      pollution is an important step in understanding the distribution of risk in a
      population and is critical for setting appropriate policies. We evaluate general
      and specific measures of community health as modifiers of risk for asthma and
      congestive heart failure following an episode of acute exposure to wildfire
      smoke. METHODS: A population-based study of emergency department visits and daily
      concentrations of fine particulate matter during a wildfire in North Carolina was
      performed. Determinants of community health defined by County Health Rankings
      were evaluated as modifiers of the relative risk. A total of 40 mostly rural
      counties were included in the study. These rankings measure factors influencing
      health: health behaviors, access and quality of clinical care, social and
      economic factors, and physical environment, as well as, the outcomes of health:
      premature mortality and morbidity. Pollutant concentrations were obtained from a
      mathematically modeled smoke forecasting system. Estimates of relative risk for
      emergency department visits were based on Poisson mixed effects regression models
      applied to daily visit counts. RESULTS: For asthma, the strongest association was
      observed at lag day 0 with excess relative risk of 66% (28,117). For congestive
      heart failure the excess relative risk was 42% (5,93). The largest difference in
      risk was observed after stratifying on the basis of Socio-Economic Factors.
      Difference in risk between bottom and top ranked counties by Socio-Economic
      Factors was 85% and 124% for asthma and congestive heart failure respectively.
      CONCLUSIONS: The results indicate that Socio-Economic Factors should be
      considered as modifying risk factors in air pollution studies and be evaluated in
      the assessment of air pollution impacts.

PMID- 23006927
TI  - Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute
      to responses that protect mice from Coccidioides immitis infection.
AB  - BACKGROUND: Coccidioidomycosis results from airborne infections caused by either
      Coccidioides immitis or C. posadasii. Both are pathogenic fungi that live in
      desert soil in the New World and can infect normal hosts, but most infections are
      self-limited. Disseminated infections occur in approximately 5% of cases and may
      prove fatal. Mouse models of the disease have identified strains that are
      resistant (e.g. DBA/2) or susceptible (e.g. C57BL/6) to these pathogens. However,
      the genetic and immunological basis for this difference has not been fully
      characterized. RESULTS: Microarray technology was used to identify genes that
      were differentially expressed in lung tissue between resistant DBA/2 and
      sensitive C57BL/6 mice after infection with C. immitis. Differentially expressed
      genes were mapped onto biological pathways, gene ontologies, and protein
      interaction networks, which revealed that innate immune responses mediated by
      Type II interferon (i.e., IFNG) and the signal transducer and activator of
      transcription 1 (STAT1) contribute to the resistant phenotype. In addition,
      upregulation of hypoxia inducible factor 1A (HIF1A), possibly as part of a larger
      inflammatory response mediated by tumor necrosis factor alpha (TNFA), may also
      contribute to resistance. Microarray gene expression was confirmed by real-time
      quantitative PCR for a subset of 12 genes, which revealed that IFNG HIF1A and
      TNFA, among others, were significantly differentially expressed between the two
      strains at day 14 post-infection. CONCLUSION: These results confirm the finding
      that DBA/2 mice express more Type II interferon and interferon stimulated genes
      than genetically susceptible strains and suggest that differential expression of
      HIF1A may also play a role in protection.

PMID- 23006929
TI  - A volumetric study of basal ganglia structures in individuals with early-treated
      phenylketonuria.
AB  - Whereas the impact of early-treated phenylketonuria (ETPKU) on cortical white
      matter is well documented, relatively little is known regarding the potential
      impact of this metabolic disorder on deep gray matter structures such as the
      basal ganglia. The current study used high-resolution (1mm(3)) magnetic resonance
      imaging to investigate bilateral basal ganglia structures (i.e., putamen, caudate
      nucleus, and nucleus accumbens) in a sample of 13 individuals with ETPKU and a
      demographically-matched sample of 13 neurologically intact individuals without
      PKU. Consistent with previous research, we found smaller whole brain volumes in
      the ETPKU group compared with the non-PKU group. Individuals with ETPKU also had
      significantly larger putamen volumes than non-PKU individuals. In addition, the
      degree of putamen enlargement was correlated with blood phenylalanine levels and
      full scale IQ in the ETPKU group. These findings are consistent with the
      hypothesis that ETPKU-related increases in phenylalanine lead to decreased
      central dopamine levels thus impacting dopamine-dependent brain regions such as
      the putamen that play an important role in cognition.

PMID- 23006930
TI  - Therapy-related acute myeloid leukemia in Crohn's disease.

PMID- 23006932
TI  - Retinal vascular caliber measurements: clinical significance, current knowledge
      and future perspectives.
AB  - The retinal vasculature provides a unique window to assess vascular health
      noninvasively and directly in vivo. Advances in fundus photography and retinal
      image analysis techniques have enabled the objective and accurate assessment of
      quantitative retinal vascular caliber measurement. Over the last decade, large
      population-based studies have shown that retinal vascular calibers are associated
      with a wide range of subclinical (e.g. atherosclerosis, inflammation and
      endothelial dysfunction) and clinical cardiovascular diseases (hypertension,
      diabetes mellitus, stroke, kidney and heart diseases). However, while retinal
      image analysis provided exciting possibilities to study the pathogenesis of these
      diseases, its direct applicability in a clinical setting as a 'test' to predict
      cardiovascular diseases is yet to be established, particularly within the context
      of being used as a population screening tool. Nevertheless, with continual
      development of retinal imaging techniques and newer understanding of the clinical
      significance of these retinal changes, there remains scope for the development of
      retinal vascular caliber measurements as a biomarker for vascular disease risk
      assessment in targeted areas and patient subgroups (e.g. patients with diabetes,
      suspected hypertension and stroke).

PMID- 23006931
TI  - No association between dietary patterns and depressive symptoms among a community
      dwelling population in Japan.
AB  - BACKGROUND: Studies of the associations between diet and depression have
      primarily focused on single nutrients or foods. Recently, dietary patterns
      representing a combination of foods have attracted more interest than individual
      nutrient. The objective of this study was to examine the association between
      dietary patterns and depressive symptoms among a community-dwelling population in
      Japan. METHODS: We examined the association between dietary patterns and the risk
      of depression among 791 Japanese community-dwelling individuals. Diet was
      assessed with a validated brief-type self-administered diet history questionnaire
      (BDHQ). Dietary patterns from 52 predefined food groups [energy-adjusted food
      (g/d)] were extracted by principal component analysis. The Center for
      Epidemiologic Studies Depression Scale (CES-D) with a cut-off point of 16 was
      used to assess the prevalence of depression. RESULTS: A total of 97 subjects
      (12.3%) were classified as having depression. Four dietary patterns were
      identified: "Healthy", "Western", "Bread and confectionery", and "Alcohol and
      accompanying" dietary patterns. After adjusting for potential confounders, the
      dietary patterns were not related to the risk of depression. CONCLUSIONS: The
      present study failed to find associations between dietary patterns and the risk
      of depression. However, the interpretation of our results was hampered by the
      lack of certain data, including employment physical activity and longitudinal
      observations. Potential associations between dietary patterns and depressive
      symptoms were not completely ruled out. Future research exploring dietary
      patterns and depressive symptoms is warranted.

PMID- 23006933
TI  - Sericin cream reduces pruritus in hemodialysis patients: a randomized, double
      blind, placebo-controlled experimental study.
AB  - BACKGROUND: Uremic pruritus (UP) is a significant complication in ESRD patients
      and substantially impairs their quality of life. UP is considered to be a skin
      manifestation of chronic inflammation. Because sericin can suppress the release
      of pro-inflammatory cytokines, the purpose of this study was to investigate the
      short-term safety and efficacy of sericin cream for treating UP in hemodialysis
      patients. METHODS: This study used a double-blind design to investigate the
      effects of random topical administration of sericin cream and cream base
      (placebo) on either the right or left extremities of hemodialysis patients for 6
      weeks. Skin hydration, irritation and pigmentation were evaluated every 2 weeks
      using Skin Diagnostic SD27. The visual analog scale for itching was also
      evaluated every 2 weeks, and the Kidney Disease Quality of Life Short Form was
      performed on the day of each patient's enrollment and after 6 weeks of treatment.
      RESULTS: Fifty dialysis patients were enrolled, 47 of which completed the study.
      The hydration of the skin of the patients' extremities increased significantly
      after administration of sericin cream; significant differences were found between
      sericin treatment and control after 6 weeks of treatment (p = 0.041 for arms and
      p = 0.022 for legs, respectively). Moreover, a significant difference was also
      found in skin irritation between the two treatments (p = 0.013 for arms and p =
      0.027 for legs, respectively). At the end of the study, the skin pigmentation
      level was significantly reduced on both the arms (p = 0.032) and legs (p = 0.021)
      of the sericin-treated side compared with the side treated with cream base. The
      mean itching score decreased significantly from moderate to severe at the time of
      enrollment to mild pruritus after 6 weeks of treatment (p = 0.002). A better
      quality of life was found in all domains tested although statistically
      significant differences before and after treatment was found only in the
      patients' pain scores, the effect of kidney disease on daily life, sleep quality
      and symptoms or problems related to kidney disease. CONCLUSIONS: We conclude that
      sericin cream has a high potential for reducing UP in hemodialysis patients.The
      trial registration number of this study is ISRCTN16019033; its public title is
      "sericin cream reduces pruritus in hemodialysis patients".

PMID- 23006936
TI  - Serum production against Tityus serrulatus scorpion venom using cross-linked
      chitosan nanoparticles as immunoadjuvant.
AB  - Several species of scorpions are known to cause accidents which can lead to
      death, most of them belonging to the genus Tityus. Tityus serrulatus is
      considered the most dangerous scorpion in South America. In Brazil, T. serrulatus
      is responsible for serious accidents, including deaths, which occur mainly with
      children and elderly people. Anti-scorpion sera are routinely produced by various
      institutions, and suitable technologies have been investigated for encapsulation
      and release recombinant or native proteins capable of inducing antibody
      production. In this context, biocompatible and biodegradable polymers, such as
      chitosan, have been employed for this purpose. This study aimed to obtain a
      protein release system for the peptides or proteins from T. serrulatus, based on
      cross-linked chitosan nanoparticles (CN) in order to generate a new model of
      immunization in animals, and consequently a potentially novel polyclonal serum,
      namely an anti-T. serrulatus venom. CN were successfully obtained by ionic
      gelation using the polyanion tripolyphosphate (TPP), which demonstrated a
      suitable particle size of about 200 nm, with maximum encapsulation efficiency
      (100%) and enhanced antigen-specific antibody titers of 72%. The serum production
      data revealed that CN were equipotent to aluminum hydroxide, the traditional
      adjuvant for immunization. This study demonstrates that chitosan nanoparticles
      are a promising and safe system for peptide/protein delivery for T. serrulatus
      scorpion.

PMID- 23006935
TI  - Greater precision when measuring dementia severity: establishing item parameters
      for the Clinical Dementia Rating Scale.
AB  - BACKGROUND/AIMS: An item response theory (IRT)-based scoring approach to the
      Clinical Dementia Rating Scale (CDR) can account for the pattern of scores across
      the CDR items (domains) and their differential abilities to indicate dementia
      severity. In doing so, an IRT-based approach can provide greater precision than
      other CDR scoring algorithms. However, neither a good set of item parameters nor
      an easily digestible set of instructions needed to implement this approach is
      readily available. METHODS: Participants were 1,326 patients at the Baylor
      College of Medicine Alzheimer's Disease and Memory Disorders Clinic. RESULTS: The
      item parameters necessary for an IRT-based scoring approach were identified (a
      parameters ranged from 3.01 to 6.22; b parameters ranged from -2.46 to 2.07).
      CONCLUSION: This study provides, and demonstrates how to easily apply, IRT-based
      item parameters for the CDR

PMID- 23006937
TI  - Thrombocytopenia in relation to tumor size in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) size at diagnosis is important in
      management. Without screening programs, tumor size at diagnosis is heterogeneous.
      AIMS: To examine the clinical parameters related to tumor size. METHODS: Using
      prospectively collected data from a 1,100-patient biopsy-proven HCC cohort
      presenting in the absence of screening, tumor sizes were ordered and
      trichotomized and the resulting terciles were compared for tumor and blood
      parameters. RESULTS: The terciles were significantly different with respect to
      portal hypertension and thrombocytopenia, which were present in a higher percent
      of tercile I patients with smaller tumors. Tercile III patients with larger HCCs
      had the highest serum alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase
      (GGTP), and alkaline phosphatase (ALKP) levels and the most portal vein (PV)
      thrombosis. Subclassification of tercile I patients by AFP showed that patients
      with high serum AFP had increased numbers of tumor nodules, more PV thrombosis,
      higher bilirubin, ALKP, and GGTP levels, and shorter survival. CONCLUSIONS:
      Smaller-tumor tercile I patients had more advanced portal hypertension with
      thrombocytopenia than did larger-tumor patients. Tercile I patients with higher
      AFP levels had more frequent PV thrombosis and worse survival than those with
      lower AFP levels. Elevated serum GGTP and ALKP levels appear to be associated
      with a more aggressive HCC phenotype. These differing patterns suggest more than
      one HCC pathway.

PMID- 23006938
TI  - Mutation specific antibodies: tool or dinosaur?
AB  - Mutation specific antibodies demonstrate the benefit of merging molecular
      findings with traditional diagnostic expertise. Whether this approach is of
      sustainable benefit has to be seen. Convincing data on colon carcinoma will be
      demonstrated at ESMO 2012 with the conclusion to screen patients for BRAFV600E
      for enrolment in an upcoming clinical trial combining BRAF and EGFR inhibitors.

PMID- 23006939
TI  - Estimation of absorbed dose to the kidneys in patients after treatment with 177Lu
      octreotate: comparison between methods based on planar scintigraphy.
AB  - BACKGROUND: Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used to treat
      neuroendocrine tumors with high somatostatin-receptor expression. 177Lu
      octreotate is mainly excreted via the kidneys, but to some extent, accumulates in
      the kidney cortex due to, e.g., tubular reabsorption. Renal toxicity is one of
      the main limiting factors in 177Lu-octreotate treatment. Further knowledge of the
      biodistribution and dosimetry of 177Lu-octreotate in individual patients is
      needed. The aim of this study was to estimate the absorbed dose to the kidneys
      and compare the results obtained with planar imaging and different dosimetric
      methods: (1) conjugate-view (CV) method using patient-specific kidney sizes, (2)
      PA method, based on posterior images only, (3) CV method with reduced number of
      time points (CVreduced data), and (4) CV method using standard kidney sizes
      (CVstandard size). METHODS: Totally, 33 patients each received 3.4 to 8.2 GBq of
      177Lu-octreotate up to five times, with infusion of lysine and arginine to block
      the renal uptake. Whole-body planar gamma camera images were acquired on days 0,
      1, 2, and 7. The 177Lu concentration in the kidneys was determined by the CV
      method, and the absorbed dose was estimated with patient-specific organ sizes.
      Comparison to the CV method was made using posterior images only, together with
      the influence of the number of time points and with standard organ sizes.
      RESULTS: Large interindividual variations were found in the time-activity curve
      pattern and in the absorbed dose to the kidneys using the CV method: 0.33 to 2.4
      Gy/GBq (mean =  0.80 Gy/GBq, SD = 0.30). In the individual patient, the mean
      deviation of all subsequent kidney doses compared to that of the first
      administration was 1% (SD = 19%) and 5% (SD = 23%) for the right and left
      kidneys, respectively. Excluding data for day 7 resulted in large variations in
      the absorbed dose. CONCLUSION: Large interindividual variations in kidney dose
      were found, demonstrating the need for patient-specific dosimetry and treatment
      planning.

PMID- 23006940
TI  - From the guest editor: pressing questions in the care of patients with lymphomas.

PMID- 23006941
TI  - What is the best initial therapy for a patient with symptomatic low-grade
      follicular lymphoma?
AB  - Follicular lymphoma is a diverse disease, both biologically and clinically.
      Patients may present with symptomatic or asymptomatic disease and with high or
      low tumor burden. Decisions to treat in the frontline are made based on
      histology, presence or absence of symptoms, disease burden, comorbidities,
      patient age, and patient preferences. As most patients with follicular lymphoma
      will eventually have a relapse, preservation of downstream treatment options also
      warrants consideration. One must be cognizant of toxicities and how these
      toxicities may influence later treatments. Given the number of variables, the
      decision making is often complex, and a certain amount of individualization is
      required. The goals of this review were to provide a framework for decision
      making and review the literature supporting the various options.

PMID- 23006942
TI  - Has single-agent rituximab replaced watch-and-wait for a patient with
      asymptomatic low-grade follicular lymphoma?
AB  - To date, no overall survival benefit has been proven from the immediate treatment
      of patients with asymptomatic follicular lymphoma (FL) compared with expectant
      management. Watchful waiting therefore became the standard of care, with patients
      closely monitored for symptoms or critical progression, necessitating
      commencement of active therapy. With this approach, patients could avoid the
      adverse effects of chemotherapy or radiotherapy, at least for a while. However,
      with the advent of rituximab-containing regimens, the standard of care for FL
      patients requiring treatment has been rewritten. Upfront rituximab monotherapy
      can produce impressive response rates with low associated toxicity, and a recent
      randomized trial has shown a significant delay in the need for other treatment,
      with possible improvements in quality of life. Even without the longer-term
      survival data, this has reignited the debate over initial management in FL.

PMID- 23006943
TI  - Small lymphocytic lymphoma and chronic lymphocytic leukemia: are they the same
      disease?
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western
      world, characterized by peripheral blood B-cell lymphocytosis as well as
      lymphadenopathy, organomegaly, cytopenias, and systemic symptoms. Chronic
      lymphocytic leukemia cells have a distinctive immunophenotype, and the disease
      has a characteristic pattern of histological infiltration in the lymph node and
      bone marrow. The clinical course of CLL is heterogeneous, with some patients
      presenting with very indolent disease and other patients having a more aggressive
      malignancy. It is known that genetic abnormalities underlie this difference in
      clinical presentation. Some patients may present solely with lymphadenopathy,
      organomegaly, and presence of infiltrating monoclonal B cells with the same
      immunophenotype as CLL cells, but lacking peripheral blood lymphocytosis. This
      disease is called small lymphocytic lymphoma (SLL) and has been considered for
      almost 2 decades to be the tissue equivalent of CLL. Both CLL and SLL are
      currently considered different manifestations of the same entity by the fourth
      edition of the World Health Organization Classification of Tumours of
      Haematopoietic and Lymphoid Tissues. It is suspected that differential expression
      of chemokine receptors (e.g., reduced expression of R1 and CCR3 in SLL cells),
      integrins (e.g., CLL cells have lower expression of integrin alphaLbeta2), and
      genetic abnormalities (a higher incidence of trisomy 12 and lower incidence of
      del(13q) is found in SLL) may explain some of the clinical differences between
      these 2 disorders. However, there is still a lack of knowledge on the precise
      biological basis underlying the different clinical presentations of CLL and SLL.
      It is expected that future studies will shed light on the pathophysiology of both
      disorders.

PMID- 23006944
TI  - Inhibitors of B-cell receptor signaling for patients with B-cell malignancies.
AB  - The B-cell receptor (BCR) complex and its associated protein tyrosine kinases
      play a critical role in the development, proliferation, and survival of normal or
      malignant B cells. Regulated activity of the BCR complex promotes the expansion
      of selected B cells and the deletion of unwanted or self-reactive ones. Compounds
      that inhibit various components of this pathway, including spleen tyrosine
      kinase, Bruton's tyrosine kinase, and phosphoinositol-3 kinase, have been
      developed. We summarize the rationale for use of agents that can inhibit BCR
      signaling to treat patients with either indolent or aggressive B-cell lymphomas,
      highlight early clinical results, and speculate on the future application of such
      agents in the treatment of patients with various B-cell lymphomas.

PMID- 23006946
TI  - Chemotherapy alone for localized diffuse large B-cell lymphoma.
AB  - Approximately 25% to 30% of patients with diffuse large B-cell lymphoma (DLBCL)
      present with limited-stage disease, typically defined as those with nonbulky (<10
      cm) Ann Arbor stage I or II disease, without B-symptoms and with sites that can
      be encompassed within a radiation field. A variety of treatment approaches have
      been used, which have largely relied on the administration of systemic therapy
      followed by involved-field radiation therapy (IFRT) to all sites of disease. The
      use of IFRT has been associated with improved local control, but a significant
      impact on long-term outcome has not been demonstrated. Although the inclusion of
      IFRT may allow for an abbreviated course of chemotherapy to be administered, this
      benefit must be weighed against the potential for radiation-induced acute and
      delayed toxicity. With the advent of improved systemic therapy, the routine use
      of IFRT in all patients with limited-stage DLBCL seems no longer justifiable. A
      tailored-therapy approach, with choice of treatment guided by patient performance
      status and chemotherapy tolerance, sites of disease involvement, clinical risk
      factors, and early treatment response would seem rational. Ultimately, greater
      biologic insight into the heterogeneity of DLBCL will likely result in a
      personalized treatment approach that relies more on biologic characteristics than
      stage of disease.

PMID- 23006945
TI  - The histological and biological spectrum of diffuse large B-cell lymphoma in the
      World Health Organization classification.
AB  - Diffuse large B-cell lymphomas (DLBCLs) are aggressive B-cell lymphomas that are
      clinically, pathologically, and genetically diverse, in part reflecting the
      functional diversity of the B-cell system. The focus in recent years has been
      toward incorporation of clinical features, morphology, immunohistochemistry, and
      ever evolving genetic data into the classification scheme. The 2008 World Health
      Organization classification reflects this complexity with the addition of several
      new entities and variants. The discovery of distinct subtypes by gene expression
      profiling heralded a new era with a focus on pathways of transformation as well
      as a promise of more targeted therapies, directed at specific pathways. Some
      DLBCLs exhibit unique clinical characteristics with a predilection for specific
      anatomic sites; the anatomic site often reflects underlying biological
      distinctions. Recently, the spectrum of Epstein-Barr virus (EBV)-driven B-cell
      proliferations in patients without iatrogenic or congenital immunosuppression has
      been better characterized; most of these occur in patients of advanced age and
      include Epstein-Barr virus (EBV)-positive large B-cell lymphoma of the elderly.
      Human herpesvirus 8 is involved in the pathogenesis of primary effusion lymphoma,
      which can present as a "solid variant." Two borderline categories were created;
      one deals with tumors at the interface between classic Hodgkin lymphoma and
      DLBCL. The second confronts the interface between Burkitt lymphoma and DLBCL, so
      called "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL
      and Burkitt lymphoma" in the 2008 classification. Most cases harbor both MYC and
      BCL2 translocations and are highly aggressive. Another interesting entity is
      anaplastic lymphoma kinase-positive DLBCL, which renders itself potentially
      targetable by anaplastic lymphoma kinase inhibitors. Ongoing investigations at
      the genomic level, with both exome and whole-genome sequencing, are sure to
      reveal new pathways of transformation in the future.

PMID- 23006947
TI  - Autotransplantation for mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) represents about 5% to 9% of all non-Hodgkin lymphomas
      according to the World Health Organization. The clinical presentation typically
      consists of diffuse lymphadenopathy and frequent extranodal involvement of the
      gastrointestinal tract, blood, and bone marrow, as well as frequent splenomegaly.
      The median survival with standard immunochemotherapy is approximately 3 to 5
      years. High-dose chemotherapy and autologous stem cell transplantation (ASCT)
      have been used either in first partial or complete remission or at the time of
      relapse in an attempt to prolong the survival for patients with MCL. Autologous
      SCT has had disappointing results in patients with relapsed MCL with the expected
      progression-free survival approximately 20% to 40% in most trials. Therefore,
      most centers now consider ASCT for eligible MCL patients during first remission.
      If a complete remission can be obtained with the induction chemotherapy, the
      clinical results following ASCT in complete remission 1 are improved to 60% to
      80% progression-free survival greater than 5 years. However, the median age of
      patients with MCL is older than 60 years, which does not allow ASCT to be used in
      all patients with MCL. Research is now focused on reducing the relapse rate after
      transplantation.

PMID- 23006948
TI  - Adult lymphoblastic lymphoma.
AB  - Adult lymphoblastic lymphoma (LBL) is an aggressive form of non-Hodgkin lymphoma
      occurring in predominantly adolescent and young adult men. Lymphoblastic lymphoma
      is rare, accounting for 1% to 2% of all non-Hodgkin lymphomas and is of T-cell
      phenotype in 90% of cases. Lymphoblastic lymphoma is morphologically indistinct
      from acute lymphoblastic leukemia (ALL). Both express their lineage-specific
      markers as well as terminal deoxynucleotidyl transferase. The differences are
      often made on clinical grounds. Lymphoblastic lymphoma is characterized by a
      predominantly nodal distribution of disease, often with a large mediastinal mass.
      Patients with less than 25% bone marrow involvement have typically been
      categorized as LBL rather than ALL, although this has not been applied
      consistently in the literature. Gene expression studies have identified
      differences in gene expression, with LBL expressing higher levels of genes
      associated with cytoskeleton, adhesion, angiogenesis, and chemotaxis than ALL.
      Although LBL and ALL can be distinct clinically, chemotherapy strategies are
      often very similar. Acute lymphoblastic leukemia regimens, which incorporate
      intensive multidrug induction, consolidation, delayed intensification, and
      maintenance, have been shown to be superior to standard lymphoma regimens. As
      central nervous system (CNS) relapse is common, CNS prophylaxis with high-dose
      chemotherapy and intrathecal therapy is also standard. The prophylactic use of
      CNS irradiation has declined with the introduction of chemotherapy regimens
      incorporating high doses of CNS-penetrating drugs such as cytarabine and
      methotrexate. The use of consolidative radiation to the mediastinum remains
      uncertain. High-dose chemotherapy followed by autologous or allogeneic
      transplantation as consolidation for patients in CR1 is controversial with modern
      intensive chemotherapy regimens, although transplantation has a proven role in
      the relapse setting.

PMID- 23006949
TI  - Management of the cutaneous peripheral T-cell lymphomas: when subtypes matter.
AB  - The cutaneous T-cell lymphomas are a heterogeneous collection of many
      biologically and clinically distinct cancers. The World Health Organization 2008
      reclassification of cutaneous lymphomas delineated provisional entities that were
      previously classified simply as primary cutaneous peripheral T-cell lymphoma not
      otherwise specified. Because of the relative rarity of cases, standard treatment
      recommendations and algorithms are lacking. However, identification of these
      subtypes is important as they can have vastly different clinical outcomes.
      Furthermore, cytokine treatments effective in classic mycosis fungoides or Sezary
      syndrome not only are ineffective, but also may exacerbate certain subtypes. The
      aim of this review was to summarize the biological bases of the recently defined
      entities, reinforce the importance of acute clinical/pathologic diagnosis, and
      propose treatment strategies based on the available data.

PMID- 23006950
TI  - Should patients with aggressive peripheral T-cell lymphoma all be treated the
      same?: no... well yes, ...but maybe not for long.
AB  - The peripheral T-cell lymphomas represent about 15% to 20% of non-Hodgkin
      lymphomas and are marked by clinical and pathologic heterogeneity. The most
      common T-cell entities include peripheral T-cell lymphoma, not otherwise
      specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma
      anaplastic lymphoma kinase-negative, which account for approximately 60% of T
      cell lymphoma cases. Because of the rarity of T-cell lymphomas and lack of
      randomized prospective studies, treatment for these diseases is not well defined.
      Current treatment strategies draw from data from phase II studies, retrospective
      analyses, and personal experience. For fit patients who can tolerate treatment
      with curative intent, we treat peripheral T-cell lymphoma, not otherwise
      specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma
      anaplastic lymphoma kinase-negative similarly with CHOP (cyclophosphamide,
      doxorubicin, vincristine, and prednisone)-based induction therapy followed by
      consolidation with autologous stem cell transplant. Given the marked differences
      in histology, biology, and clinical presentation for these diseases, it is likely
      that they should be approached differently. Furthermore, prognostic factors and
      degree of chemosensitivity as measured by FDG-PET (fluorodeoxyglucose positron
      emission tomography) should likely be used to guide patients along different
      treatment pathways. We have a long way to go toward perfecting the treatment for
      T-cell lymphoma. We believe that a uniform treatment approach for patients with
      aggressive T-cell lymphoma is not appropriate; however, we do not yet have enough
      data to support an individualized approach to treatment. Clinical and biologic
      prognostic factors, degree of chemosensitivity as measured by FDG-PET, and
      histology should all likely have a role in directing patients along different
      treatment pathways, but prospective studies are needed to confirm this.

PMID- 23006951
TI  - Brentuximab vedotin and crizotinib in anaplastic large-cell lymphoma.
AB  - Systemic anaplastic large-cell lymphoma (ALCL) is a rare, mature T-cell non
      Hodgkin lymphoma. Anaplastic large-cell lymphoma cells express the surface
      antigen CD30, and more than half express the anaplastic lymphoma kinase (ALK)
      protein. These 2 proteins provide unique therapeutic targets in ALCL. Remission
      rates in ALCL with combination chemotherapy are approximately 80%, but relapse
      after first-line therapy is common. Brentuximab vedotin is a US Food and Drug
      Administration-approved, antibody-drug conjugate that combines an anti-CD30
      antibody with monomethylauristatin E, a potent antimicrotubule agent. Response
      rates to brentuximab vedotin in patients with relapsed/refractory ALK and ALK
      ALCL have exceeded 80% with frequent complete responses and a median duration of
      response greater than 1 year. Brentuximab vedotin in combination with
      chemotherapy is being explored as a first-line therapy in ALCL. Crizotinib is an
      inhibitor of ALK tyrosine kinase that has been approved for the treatment of ALK
      non-small cell lung cancer. Successful treatment of ALK ALCL with crizotinib has
      been reported in pediatric patients and small case series leading to ongoing
      trials in relapsed/refractory ALCL. Brentuximab vedotin and crizotinib represent
      major advances in the treatment of ALK and ALK ALCL and will likely result in
      marked improvement in prognosis for this subset of aggressive lymphomas.

PMID- 23006952
TI  - Nonmyeloablative allogeneic stem cell transplantation for non-hodgkin lymphoma.
AB  - Non-Hodgkin lymphomas constitute a heterogeneous group of hematologic
      malignancies with varying aggressiveness and many therapeutic options.
      Nonmyeloablative (NMA) conditioning has been the cornerstone of allogeneic
      adoptive immunotherapy for these diseases. This approach utilizes a reduced
      intensity preparative regimen to achieve engraftment with little toxicity. This
      allows for development of the immune graft-versus-lymphoma effect. Results depend
      on the histologic type of lymphoma, prognostic factors, patient characteristics,
      and chemosensitivity. For follicular lymphomas, NMA transplants are highly
      effective in patients with refractory or recurrent disease after the best
      chemoimmunotherapy available and who have a matched sibling or unrelated donor.
      In mantle cell lymphoma, autologous stem cell transplants are generally
      ineffective for patients with recurrent disease; we reported 6-year actuarial
      progression-free survival rate of 46%, using NMA allogeneic transplants. The
      indications of NMA transplants for diffuse large B-cell lymphoma and T-cell
      lymphomas are controversial; success has been reported in selected high-risk
      patients and those relapsing after an autologous transplantation who have
      chemosensitive disease. Considerations for the conditioning regimen, donor
      source, graft-versus-host disease prophylaxis, donor lymphocyte infusion, and
      relapse prevention methods are reviewed.

PMID- 23006953
TI  - Diagnosis and management of neurolymphomatosis.
AB  - Invasion of cranial nerves and peripheral nerve roots, plexus, or nerves by non
      Hodgkin lymphoma is denoted as neurolymphomatosis (NL). Four clinical patterns
      are recognized. Most commonly, NL presents as a painful polyneuropathy or
      polyradiculopathy, followed by cranial neuropathy, painless polyneuropathy, and
      peripheral mononeuropathy. Diagnosis of NL is challenging and requires
      integration of clinical information, imaging findings, and histopathologic
      examination of involved nerves or nonneural tissue and cerebrospinal fluid
      analysis. In the rare cases of primary NL, the diagnosis is often delayed.
      Successful therapy is contingent upon recognition of the disease and its exact
      neuroanatomic localization without delay. Treatment options include systemic
      chemotherapy and localized irradiation of bulky disease sites. Concomitant
      involvement of cerebrospinal fluid and systemic disease sites requires more
      complex regimens.

PMID- 23006954
TI  - Lymphomatoid granulomatosis.
AB  - Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV)-driven
      lymphoproliferative disease. The atypical lymphoid cells directly accumulate
      within affected tissues and clinically present in the form of infiltrative
      lesions. It is usually a progressive disorder that virtually always involves the
      lung and characteristically presents as bilateral pulmonary nodules. Other
      commonly affected organ systems include the skin, central nervous system, and
      kidneys. The rareness of LYG in conjunction with its nonspecific presentation
      contributes to delays in diagnosis in many situations. Pathologically, it is
      characterized by the presence of an angiocentric and angiodestructive
      accumulation of varying numbers of T cells with varying numbers of atypical
      clonal EBV-positive B cells in a polymorphous inflammatory background. It can be
      subclassified using a grading system based on the number of EBV-positive large B
      cell malignant cells, which is critical in selecting appropriate management
      strategies. Lower-grade LYG occasionally undergoes spontaneous remission and is
      best managed with strategies designed to enhance the host's underlying immune
      system, whereas high-grade LYG is best managed by combination chemoimmunotherapy
      but has inferior outcomes. Lymphomatoid granulomatosis can lead to progressive
      pulmonary failure, central nervous system disease, or progression to overt EBV
      positive lymphoma without appropriate recognition and management. Improvements in
      the modern understanding of the biology of LYG, particularly the precise role of
      EBV in its pathogenesis, offer promise in the development of improved management
      strategies.

PMID- 23006955
TI  - [What to do in case of adverse event in recipient at the French National Blood
      Service?].
AB  - One of the main goals of haemovigilance is to gather and analyze adverse events
      in recipients of blood products in order to improve blood safety. The French
      National Blood Service has a specific role in the management of immediate adverse
      events: to alert to quarantine the potentially dangerous blood products from the
      same donation(s), to provide blood testing for the etiologic assessment and to
      give transfusion advice to patients. The updating of the recipient's computer
      file allows a better monitoring for both immediate and delayed adverse events.
      Finally, the French National Blood Service's correspondent of haemovigilance is
      responsible for donor's inquiries, especially in cases of transfusion related to
      bacterial contamination, severe allergy, suspicion of transfusion acute related
      lung injury and viral seroconversion. The management effectiveness for adverse
      events requires a strong collaboration between all members of the haemovigilance
      network.

PMID- 23006956
TI  - Frequency of group A rotavirus with mixed G and P genotypes in bovines:
      predominance of G3 genotype and its emergence in combination with G8/G10 types.
AB  - The present study describes the genotypic distribution of rotaviruses (RVs) in an
      Indian bovine population with unexpectedly higher proportions of G3 alone or in
      combination of G8/G10. PCR-genotyping confirmed that 39.4% (13/33) of the
      prevalent RVs were the G3 type while 60.6% (20/33) were dual G3G10 or G3G8 types.
      P typing revealed that 93.9% (31/33) of the samples were P[11] while 6.1% (2/33)
      possessed a dual P[1]P[11] type.  Sequence analysis of the VP7 gene from G3
      strains viz. B-46, 0970, and BR-133 showed that these strains had sequence
      identities of 90.5% to 100% with other bovine G3 strains. The highest identity
      (98.9% to 100%) was observed with RUBV3 bovine G3 strains from eastern India. The
      G3 strains (B-46, 0970, and BR-133) showed 97.5% to 98.8% sequence homologies
      with the Indian equine RV strain Erv-80. Phylogenetic analysis demonstrated that
      G3 strains clustered with bovine RUBV3 and J-63, and equine Erv-80 G3. Overall,
      these results confirmed that the incidence of infection by RVs with the G3
      genotype and mixed genotypes in the bovine population was higher than previously
      predicted. This finding reinforces the importance of constantly monitoring
      circulating viral strains with the G3 genotype in future surveillance studies.

PMID- 23006957
TI  - Death of a son is associated with risk of suicide among parous women in Taiwan: a
      nested case-control study.
AB  - BACKGROUND: The impact of the sex of a deceased child on maternal suicide has not
      been studied. We examined whether the death of a child, especially a son,
      increased the risk of suicide among parous Taiwanese women. METHODS: This matched
      case-control study was done within a cohort of 1 292 462 Taiwanese women who
      experienced a first and singleton childbirth between 1 January 1978 and 31
      December 1987 and were followed up until 31 December 2008. From the cohort, 2701
      suicide cases were identified and 2701 controls were randomly selected. Multiple
      logistic regression was used to estimate the risk of suicide associated with the
      death of a child. RESULTS: The adjusted odds ratios (ORs) for suicide among
      mothers whose son had died were 2.60 (95% CI = 1.18-5.73), 2.58 (1.28-5.20), and
      4.20 (0.79-22.45) for death of a son aged younger than 1 year, 1 to 17 years, and
      18 years or older. The ORs for suicide associated with the death of a daughter
      were not statistically significant: the respective adjusted ORs were 1.86 (0.82
      4.62), 1.38 (0.54-3.49), and 2.48 (0.40-15.51). CONCLUSIONS: The death of a
      child, especially a son, increased the risk of maternal suicide, which supports
      the notion that preference for a son is firmly rooted in traditional Chinese
      culture.

PMID- 23006958
TI  - Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes
      mellitus on HbA1c in the Japanese general population.
AB  - BACKGROUND: Although the peroxisome proliferator-activated receptor-gamma2
      (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the
      associations and interactions of this polymorphism and known clinical risk
      factors with glycated hemoglobin (HbA1c) remain poorly understood. We
      investigated if carrying the Ala allele was inversely associated with HbA1c level
      and examined possible interactions. METHODS: This cross-sectional analysis used
      data collected from 1281 men and 1356 women aged 40 to 69 years who completed the
      baseline survey of the Japan Multi-Institutional Collaborative Cohort Study.
      PPARG2 polymorphism was determined by multiplex polymerase chain reaction (PCR)
      based Invader assay. Multiple linear regression and ANCOVA were used to control
      for confounding variables (age, body mass index [BMI], energy intake, alcohol,
      smoking, physical activity, and family history of diabetes) and examine possible
      interactions. RESULTS: After adjustment, the Ala allele was significantly
      inversely associated with HbA1c in women but not in men. Older age, BMI, and
      family history of diabetes were associated with higher HbA1c in both sexes. When
      stratified by PPARG2 genotype, these associations were observed in subjects with
      the Pro12Pro genotype but not in Ala allele carriers. A significant interaction
      of genotype and BMI on HbA1c was observed in women. Older age, BMI, and family
      history of diabetes were significantly associated with high-normal HbA1c (>=5.7%
      NGSP), whereas PPARG2 polymorphism was not. CONCLUSIONS: Although PPARG2 Pro12Ala
      polymorphism might attenuate associations between known risk factors and HbA1c
      level, it had a small effect on high-normal HbA1c, as compared with clinical risk
      factors, in the general population.

PMID- 23006959
TI  - JAK2 V617F-mutated myeloproliferative neoplasia developing five years after wild
      type JAK2 acute myeloid leukemia: a case report.

PMID- 23006960
TI  - A randomized controlled trial of long term effect of BCM guided fluid management
      in MHD patients (BOCOMO study): rationales and study design.
AB  - BACKGROUND: Bioimpedance analysis (BIA) has been reported as helpful in
      identifying hypervolemia. Observation data showed that hypervolemic maintenance
      hemodialysis (MHD) patients identified using BIA methods have higher mortality
      risk. However, it is not known if BIA-guided fluid management can improve MHD
      patients' survival. The objectives of the BOCOMO study are to evaluate the
      outcome of BIA guided fluid management compared with standard care. METHODS: This
      is a multicenter, prospective, randomized, controlled trial. More than 1300
      participants from 16 clinical sites will be included in the study. The enrolment
      period will last 6 months, and minimum length of follow-up will be 36 months. MHD
      patients aged between 18 years and 80 years who have been on MHD for at least 3
      months and meet eligibility criteria will be invited to participate in the study.
      Participants will be randomized to BIA arm or control arm in a 1:1 ratio. A
      portable whole body bioimpedance spectroscopy device (BCM-Fresenius Medical Care
      D GmbH) will be used for BIA measurement at baseline for both arms of the study.
      In the BIA arm, additional BCM measurements will be performed every 2 months. The
      primary intent-to-treat analysis will compare outcomes for a composite endpoint
      of death, acute myocardial infarction, stroke or incident peripheral arterial
      occlusive disease between groups. Secondary endpoints will include left
      ventricular wall thickness, blood pressure, medications, and incidence and length
      of hospitalization. DISCUSSIONS: Previous results regarding the benefit of strict
      fluid control are conflicting due to small sample sizes and unstable dry weight
      estimating methods. To our knowledge this is the first large-scale, multicentre,
      prospective, randomized controlled trial to assess whether BIS-guided volume
      management improves outcomes of MHD patients. The endpoints of the BOCOMO study
      are of utmost importance to health care providers. In order to obtain that aim,
      the study was designed with very careful important considerations related to the
      endpoints, sample size, inclusion criteria, exclusion criteria and so on. For
      example, annual mortality of Beijing MHD patients was around 10%. To reach
      statistical significance, the sample size will be very large. By using composite
      endpoint, the sample size becomes reasonable and feasible. Limiting inclusion to
      patients with urine volume less than 800 ml/day the day before dialysis session
      will limit confounding due to residual renal function effects on the measured
      parameters. Patients who had received BIS measurement within 3 months prior to
      enrolment are excluded as data from such measurements might lead to protocol
      violation. Although not all patients enrolled will be incident patients, we will
      record the vintage of dialysis in the multivariable analysis.

PMID- 23006961
TI  - Des-gamma-carboxy prothrombin and c-Met were concurrently and extensively
      expressed in hepatocellular carcinoma and associated with tumor recurrence.
AB  - The aim of this study was to investigate co-expression of des-gamma-carboxy
      prothrombin (DCP) and c-Met in hepatocellular carcinoma (HCC) and its
      significance in predicting tumor recurrence after surgical resection.
      Immunohistochemical techniques were used to examine DCP and c-Met expression in
      HCC samples collected from 153 patients. DCP and c-Met staining were observed in
      tumor areas in 63.4% (97/153) and 66.7% (102/153) of patients, respectively, and
      these figures are markedly higher than the rates at which adjacent nontumorous
      areas tested positive of 13.1% (20/154) and 28.8% (44/153). Furthermore, DCP and
      c-Met were consistently present or absent in HCC regions in 51.0% (78/153) and
      20.9% (32/153) of patients, in adjacent nontumorous regions in 7.2% (11/153) and
      65.4% (100/153) of patients, and in whole regions including HCC and adjacent
      nontumorous regions in 58.2% (89/153) and 19.6% (30/153) of patients. These
      results indicate that DCP and c-Met usually appeared or disappeared in HCC in a
      parallel manner. c-Met was found to be related to tumor recurrence in patients
      with HCC. When combined with DCP, c-Met is more effective at predicting non
      recurrence of HCC than c-Met alone. Expression of neither DCP nor c-Met in HCC
      regions and adjacent regions signified a low rate of tumor recurrence after
      surgical resection. Results of the current study suggested that DCP and c-Met are
      commonly and concurrently expressed in HCC and their absence is associated with a
      low risk of tumor recurrence.

PMID- 23006962
TI  - Lipase, protease, and biofilm as the major virulence factors in staphylococci
      isolated from acne lesions.
AB  - Staphylococci involve infections in association with a number of bacterial
      virulence factors. Extracellular enzymes play an important role in staphylococcal
      pathogenesis. In addition, biofilm is known to be associated with their
      virulence. In this study, 149 staphylococcal isolates from acne lesions were
      investigated for their virulence factors including lipase, protease, and biofilm
      formation. Coagulase-negative staphylococci were demonstrated to present lipase
      and protease activities more often than coagulase-positive staphylococci. A
      microtiter plate method (quantitative method) and a Congo red agar method
      (qualitative method) were comparatively employed to assess biofilm formation. In
      addition, biofilm forming ability was commonly detected in a coagulase-negative
      group (97.7%, microtiter plate method and 84.7%, Congo red agar method) more
      frequently than in coagulase-positive organisms (68.8%, microtiter plate method
      and 62.5%, Congo red agar method). This study clearly confirms an important role
      for biofilm in coagulasenegative staphylococci which is of serious concern as a
      considerable infectious agent in patients with acnes and implanted medical
      devices. The Congo red agar method proved to be an easy method to quickly detect
      biofilm producers. Sensitivity of the Congo red agar method was 85.54% and 68.18%
      and accuracy was 84.7% and 62.5% in coagulase-negative and coagulase-positive
      staphylococci, respectively, while specificity was 50% in both groups. The
      results clearly demonstrated that a higher percentage of coagulasenegative
      staphylococci isolated from acne lesions exhibited lipase and protease
      activities, as well as biofilm formation, than coagulase-positive staphylococci.

PMID- 23006963
TI  - The impact of Gonoshasthaya Kendra's Micro Health Insurance plan on antenatal
      care among poor women in rural Bangladesh.
AB  - Low utilization of antenatal care (ANC) by pregnant women, particularly in rural
      areas, is an obstacle to ensuring safe motherhood in Bangladesh. Currently, Micro
      Health Insurance (MHI) is being considered in many developing countries as a
      potential method for assuring greater access to health care, especially for the
      poor. So far, there is only limited evidence evaluating MHI schemes. This study
      assesses the impact of MHI administered by Gonoshasthaya Kendra (GK) on ANC
      utilization by poor women in rural Bangladesh. We conducted a questionnaire
      survey and collected 321 valid responses from women enrolled in GK's MHI scheme
      and 271 from women not enrolled in any health insurance plan. We used a two-part
      model in which dependent variables were whether or not women utilized ANC and the
      number of times ANC was used. The model consisted of logistic regression analysis
      and ordinary least squares regression analysis. The main independent variables
      were dummies for socioeconomic classes according to GK, each of which represented
      the premiums and co-payments charged by class. The results showed that destitute,
      ultra-poor, and poor women enrolled in MHI used ANC significantly more than women
      not enrolled in health insurance. Women enrolled in MHI, except for those who
      were destitute or ultra-poor, utilized ANC significantly more times than women
      not enrolled in health insurance. We assume that GK's sliding premium and co
      payment scales are key to ANC utilization by women. Expanding the MHI scheme may
      enhance ANC utilization among poor women in rural Bangladesh.

PMID- 23006964
TI  - High quality nutrient intake is associated with higher household expenditures by
      Japanese adults.
AB  - There is little evidence of socioeconomic differences in dietary intake in the
      Japanese population. This study examined the association between household
      expenditures and dietary intake using nationally representative surveys of Japan.
      We analyzed data from the Comprehensive Survey of Living Conditions and National
      Health and Nutrition Survey, 2003-2007. For subjects ages 18 to 74 years (11,240
      men and 11,472 women), the sex-specific association between household expenditure
      quartiles and selected nutrient intake was examined using comparison of means and
      prevalence of a healthy intake. Higher household expenditures were associated
      with an increase in the mean levels of total energy, fat, protein, carbohydrates,
      calcium, vitamins A and C, niacin, and fiber for both men and women and salt for
      men. Prevalence comparison indicated that most of the recommendations for dietary
      intake were met for people with higher household expenditures than for those with
      lower household expenditures. There was no clear association between fat intake
      and expenditures. Higher household expenditures were associated with a healthy
      and balanced nutrient intake in Japanese adults. The findings suggest that
      socioeconomic differences in dietary patterns contribute to socioeconomic
      inequalities in mortality and morbidity in Japan.

PMID- 23006965
TI  - Membrane raft disruption results in neuritic retraction prior to neuronal death
      in cortical neurons.
AB  - Membrane rafts, rich in sphingolipids and cholesterol, play an important role in
      neuronal membrane domain-specific signaling events, maintaining synapses and
      dendritic spines. The purpose of this study is to examine the neuronal response
      to membrane raft disruption. Membrane rafts of 8 DIV primary neuronal cultures
      were isolated based on the resistance to Triton X-100 and ability to float in
      sucrose gradients. Membrane rafts from primary cortical neurons were also imaged
      using the membrane raft marker, cholera toxin subunit-B (CTxB), and were co
      immunolabelled with the dendritic microtubule associated protein marker, MAP-2,
      the dendritic and axonal microtubule protein, beta-III-Tubulin, and the axonal
      microtubule protein, Tau. Exposure of cortical neurons to either the cholesterol
      depleting compound, methyl-beta-cyclodextrin (MBC), or to the glycosphingolipid
      metabolism inhibiting agent D-threo-1-phenyl-2-decanoylamino-3- morpholino-1
      propanol (D-PDMP), resulted in neuritic retraction prior to the appearance of
      neuronal death. Further investigation into the effects of MBC revealed a
      pronounced perturbation of microtubule protein association with membrane rafts
      during neuritic retraction. Interestingly, stabilizing microtubules with
      Paclitaxel did not prevent MBC induced neuritic retraction, suggesting that
      neuritic retraction occurred independently of microtubule disassembly and that
      microtubule association with membrane rafts is critical for maintaining neuritic
      stability. Overall, the data indicated that membrane rafts play an important role
      in neurite stability and neuronal viability.

PMID- 23006966
TI  - Identification of novel small-molecule inhibitors of glioblastoma cell growth and
      invasion by high-throughput screening.
AB  - Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain
      tumor with a very poor prognosis. Current therapies for GBM remain palliative and
      advances made in decades have resulted in only a slight improvement in treatment
      outcome. Exploring new therapeutic agents for GBM treatment, therefore, is of
      prime importance. In the present study, we performed a high-throughput screening
      for GBM cell growth and invasion, with an attempt to identify novel potential
      anti-GBM agents. An annotated compound library (LOPAC1280) of 1,280
      pharmacologically active compounds was screened and ten compounds were validated
      and identified as inhibitors of GBM cell growth and invasion. Four of them, i.e.,
      6-nitroso-1,2-benzopyrone, S-(p-azidophenacyl) glutathione, phenoxybenzamine
      hydrochloride, and SCH-28080 have not been implicated in GBM cell growth and
      invasion previously, suggesting that they may serve as novel potential
      therapeutic agents for GBM treatment. In conclusion, novel inhibitors of GBM cell
      growth and invasion were identified in the present study, which provides a basis
      for the development of therapies for GBM, and may shed light on the molecular
      mechanisms underlying GBM cell behavior.

PMID- 23006967
TI  - Paris saponin II of Rhizoma Paridis--a novel inducer of apoptosis in human
      ovarian cancer cells.
AB  - Rhizoma Paridis (dried root and rhizome) has been an essential ingredient in
      traditional Chinese herbal medicine. In the past decade, active components of
      Rhizoma Paridis - the Paris saponins have emerged as promising anti-cancer
      agents. Among these saponins, polyphyllin D (Paris saponin (PS) I), has been
      extensively studied and proposed to be a potent antitumor agent. In this study,
      we continue to establish the efficacy and mechanisms underlying the cytotoxic
      effects of the steroidal PS members, namely formosanin C (PSII) in ovarian cancer
      treatment. We isolated PSII and evaluated its effects on a panel of ten human
      cell lines. Isolated PSII has potent inhibitory effects on the growth of tumor
      cells without deleterious effects to different normal cell types or benign
      neoplastic derived cells. While PSII, PSI, and etoposide are effective promoting
      agents for cell cycle arrest and apoptosis, PSII appeared to be marginally more
      potent than the later two in inhibiting SKOV3 cell growth. In PSII-treated SKOV3
      cells, there was an elevation in proapoptotic elements including Bax, cytosolic
      cytochrome c, activated-caspase-3, and activated-caspase-9. The treatment also
      reduced extracellular signal-regulated kinase (ERK1/2) phosphorylation and anti
      apoptotic Bcl-2 expression. We also assessed the antitumor efficacy of
      intraperitoneal administration of PSII in human SKOV3 ovarian cancer xenografts
      in athymic mice. PSII treatment significantly inhibited the growth of xenograft
      tumors relative to controls by 70% (p < 0.05). These findings demonstrated that,
      in addition to the unique selectivity against cancer cells, PSII is a potent
      antitumor molecule that may be developed as a cancer therapeutic agent.

PMID- 23006968
TI  - Effects of Chinese herbal medicine Ningdong granule on regulating dopamine
      (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA) in patients with
      Tourette syndrome.
AB  - Many studies have indicated that a variety of neurotransmitters are implicated in
      the pathophysiology of Tourette syndrome (TS), including dopamine (DA), serotonin
      (5-TH), homovanillic acid (HVA), and gamma-amino butyric acid (GABA). Our
      previous studies found that Ningdong granule (NDG) is effective on a rat model
      with TS. NDG can regulate the metabolic disturbance of DA, 5-TH and HVA in the
      rat brain. However, the mechanisms of NDG in patients with TS are still not
      clear. To further evaluate the efficiency, safety, and possible mechanisms of
      NDG, a randomized and double-blind study was carried out. One hundred and twenty
      patients with TS were enrolled in this study, that were randomly divided into 4
      groups (NDG group, Haloperidol (Hal) group, NDG + Hal group and Control group).
      First, the efficiency of NDG was assessed using the Yale Global Tic Severity
      Score (YGTSS). Second, the concentration of DA, HVA, 5-TH, 5-hydroxyindoleacetic
      acid (5-HIAA) and GABA in sera were tested by ELISA. In addition, the influence
      of NDG on liver and renal function was recorded. We found that NDG could
      ameliorate tics significantly according the YGTSS score. The concentration of HVA
      and GABA were increased after treatment with NDG. Furthermore, we found that
      there was no liver or renal damage in children treated with NDG. We also found
      that the NDG + Hal group was more effective and safe compared with other groups.
      In conclusion, the current study indicates that NDG might be effective on
      patients with TS by regulating dopamine (DA)/serotonin (5-TH) and gamma-amino
      butyric acid (GABA).

PMID- 23006969
TI  - Hyperreflective dots: a new spectral-domain optical coherence tomography entity
      for follow-up and prognosis in exudative age-related macular degeneration.
AB  - PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) enables high
      resolution analysis of retinal layers and previously unseen hyperreflective dots
      (HRD). HRD morphological characteristics, evolution, possible origin and
      prognostic value are discussed. METHODS: We conducted a prospective study of 100
      patients with exudative age-related macular degeneration (AMD), who were treated
      and followed up with monthly imaging examinations. Statistical correlations
      between visual acuity (VA) and pre-/post- treatment HRD characteristics were
      evaluated. RESULTS: HRD were present in all cases, mainly in the outer retinal
      layers but also elsewhere. After treatment, HRD regressed in a few days, 1 month
      (p < 0.04) and 3 months (p < 0.01). Regression was evident in all VA and
      morphological subsets. Resolution was associated with better final VA (p <
      0.001). CONCLUSIONS: Presence of initial/recurrent HRD, rapid treatment response
      and the growing role that early biological inflammatory reaction plays in AMD
      suggests HRD are activated microglia cells. The correlation between VA and HRD
      could make HRD a clinical marker for early decisions about treatment and
      retreatment.

PMID- 23006970
TI  - Sexual dysfunction in Assyrian/Syrian immigrants and Swedish-born persons with
      type 2 diabetes.
AB  - BACKGROUND: Few studies have investigated sexual dysfunction in immigrant
      patients with type 2 diabetes in Sweden. The aim of this study was to examine the
      association between ethnicity and sexual dysfunction and to analyze if this
      association remains after adjusting for explanatory variables including age,
      marital status, HbA1c, triglycerides, and hypertension. This cross-sectional
      study was conducted at four primary health care centers in the Swedish town of
      Sodertalje. A total of 354 persons with type 2 diabetes (173 Assyrians/Syrians
      and 181 Swedish-born patients) participated in the survey. The main outcome
      measure was the self-reported presence of sexual dysfunction based on two
      questions, one regarding loss of ability to have sexual intercourse and the other
      loss of sexual desire. Response rates were 78% and 86%, respectively. FINDINGS:
      The total prevalence of loss of ability to have intercourse was 29.5%. In the
      multivariate models, the odds of loss of ability to have intercourse was
      significantly higher in the oldest age group (OR = 5.80; 95% CI, 2.33-14.40), in
      men (OR = 3.33; 95% CI, 1.33-8.30), and in unmarried individuals (OR = 2.40; 95%
      CI, 1.02-5.70). The odds of reporting loss of sexual desire was higher in
      Assyrians/Syrians than in Swedish-born patients and increased from 2.00 in the
      age- and gender-adjusted model to 2.70 in the fully adjusted model when all
      confounders were taken into account. CONCLUSIONS: Sexual dysfunction appears to
      be more common in Assyrians/Syrians than in Swedish-born patients. Health care
      workers should actively ask about sexual function in their patients with type 2
      diabetes.

PMID- 23006972
TI  - Validity of laparoscopic staging to avoid adjuvant chemoradiation following
      radical surgery in patients with early cervical cancer.
AB  - PURPOSE: To determine the rate of unavoidable adjuvant chemoradiation (RCTX) due
      to histologic results after radical surgery in patients with early cervical
      cancer. PATIENTS AND METHODS: Between May 2004 and July 2011, 448 consecutive
      patients diagnosed with invasive cervical cancer stage IA1 L1 to IIA underwent
      laparoscopic staging at the Department of Gynecology and Gynecologic Oncology at
      Charite Berlin. Only in patients without lymph node metastases (n = 394) on
      frozen section, radical operation was continued either by laparoscopic radical
      hysterectomy (n = 228) or by radical vaginal trachelectomy (n = 166). The
      decision for adjuvant RCTX was reached among the members of an interdisciplinary
      tumor board according to the presence of risk factors. The mean age of patients
      was 39 years. Squamous cell cancer was found in 62.5%, adenocarcinoma in 32.7%,
      adenosquamous cancer in 3.8% and others in 1% of patients. Adjuvant treatment was
      indicated if at least one category 1 risk factor (pN1, R1 or RX, parametrial
      involvement) and/or any combination of category 2 risk factors (lymphovascular
      space involvement (LVSI), hemovascular space involvement, grading 3, young age,
      deep stromal invasion, large tumor size) were present. RESULTS: In 39 of 394
      patients (9.9%), adjuvant RCTX was recommended due to category 1 risk factors (n
      = 25/6.4%) and category 2 risk factors (n = 14/3.5%). Tumor-involved (R0) or
      unclear resection margins (RX) were present in 4 (1%) and 1 (0.3%), parametrial
      involvement in 12 (3%) and positive lymph nodes in 11 (2.8%) patients,
      respectively. Hemovascular involvement was found in 14 (3.5%), LVSI in 113
      (28.7%) and grading 3 in 122 (31%) patients, respectively. CONCLUSION:
      Laparoscopic staging is a reliable tool to keep the rate of tri-modal (surgery +
      chemotherapy + radiotherapy) treatments in patients with cervical cancer stage I
      and IIA after radical surgery at 10%. This percentage should be used as benchmark
      for the quality of interdisciplinary treatment of patients diagnosed with
      cervical cancer.

PMID- 23006973
TI  - Neoadjuvant chemotherapy in advanced ovarian cancer: On what do we agree and
      disagree?

PMID- 23006974
TI  - Predictors of freedom from disease activity in natalizumab treated-patients with
      multiple sclerosis.
AB  - PURPOSE: To identify baseline predictors of the response to natalizumab in
      patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We
      prospectively collected clinical and magnetic resonance imaging (MRI) data of
      RRMS patients treated with natalizumab and followed-up for 24 months. They were
      categorized according to different outcomes of response to natalizumab: (i)
      "full" responders, i.e. those having no relapses, no sustained disability
      worsening on Expanded Disability Status Scale (EDSS), and no MRI activity; (ii)
      "partial" responders, i.e. those having MRI activity, but not relapses and/or
      EDSS worsening; and (iii) "poor" responder, i.e. those experiencing relapses
      and/or EDSS worsening. RESULTS: We analysed data of 210 RR-MS patients (147 F, 63
      M); at the end of the 24-month study period, 120 (57.1%), 36 (17.1%), and 54
      (25.8%) patients were defined as "full", "partial" or "poor" responders,
      respectively. Thirty-two (89%) patients classified as "partial" responders
      experienced MRI activity at the 6-month scan; the majority of them had >2
      contrast-enhancing lesions at baseline MRI scan or >2 relapses in the year prior
      to starting therapy. A "full" response to natalizumab was found more likely in
      patients with <= 2 relapses in the year prior to treatment start (OR=3.68;
      p=0.002), and in those with an EDSS score <= 2.5 at baseline (OR=3.60; p<0.001).
      Accordingly, patients with >2 relapses in the year prior to treatment start, or
      those with an EDSS score >= 3.0 at baseline were more likely to be classified as
      "poor responders". These figures were replicated even after excluding 20 patients
      who developed anti-natalizumab antibodies. CONCLUSION: Our results suggest that
      natalizumab may lead to a complete remission of MS if started in patients with
      less aggressive disease (i.e. few relapses and mild disability), thus suggesting
      its possible role as first switching option, or even first-line therapy, at least
      in JCV-negative patients. We also support the recommendation against an immediate
      discontinuation of despite the occurrence of MRI activity in the first few months
      of treatment, since the freedom from clinical disease activity could be still
      achieved.

PMID- 23006975
TI  - Brief intervention to reduce risky drinking in pregnancy: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Risky drinking in pregnancy by UK women is likely to result in many
      alcohol-exposed pregnancies. Studies from the USA suggest that brief intervention
      has promise for alcohol risk reduction in antenatal care. However, further
      research is needed to establish whether this evidence from the USA is applicable
      to the UK. This pilot study aims to investigate whether pregnant women can be
      recruited and retained in a randomized controlled trial of brief intervention
      aimed at reducing risky drinking in women receiving antenatal care. METHODS: The
      trial will rehearse the parallel-group, non-blinded design and procedures of a
      subsequent definitive trial. Over 8 months, women aged 18 years and over (target
      number 2,742) attending their booking appointment with a community midwife (n =
      31) in north-east England will be screened for alcohol consumption using the
      consumption questions of the Alcohol Use Disorders Identification Test (AUDIT-C).
      Those screening positive, without a history of substance use or alcohol
      dependence, with no pregnancy complication, and able to give informed consent,
      will be invited to participate in the trial (target number 120). Midwives will be
      randomized in a 1:1 ratio to deliver either treatment as usual (control) or
      structured brief advice and referral for a 20-minute motivational interviewing
      session with an alcohol health worker (intervention). As well as demographic and
      health information, baseline measures will include two 7-day time line follow
      back questionnaires and the EuroQoL EQ-5D-3 L questionnaire. Measures will be
      repeated in telephone follow-ups in the third trimester and at 6 months post
      partum, when a questionnaire on use of National Health Service and social care
      resources will also be completed. Information on pregnancy outcomes and
      stillbirths will be accessed from central health service records before the
      follow-ups. Primary outcomes will be rates of eligibility, recruitment,
      intervention delivery, and retention in the study population, to inform power
      calculations for a definitive trial. The health-economics component will
      establish how cost-effectiveness will be assessed, and examine which data on
      health service resource use should be collected in a main trial. Participants'
      views on instruments and procedures will be sought to confirm their
      acceptability. DISCUSSION: The study will produce a full trial protocol with
      robust sample-size calculations to extend evidence on effectiveness of screening
      and brief intervention. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN43218782.

PMID- 23006977
TI  - Longitudinal changes in primary progressive aphasias: differences in cognitive
      and dementia staging measures.
AB  - BACKGROUND/AIMS: The longitudinal course of three primary progressive aphasia
      (PPA) variants was examined using Addenbrooke's Cognitive Examination-Revised
      (ACE-R) and the Frontotemporal dementia Rating Scale (FRS). METHODS: Cases with
      two assessments on the ACE-R and FRS were selected. A total of 220 assessments
      were obtained on 55 patients: 17 Alzheimer's disease (AD) and 38 PPA [17 semantic
      variant (svPPA), 12 non-fluent/agrammatic (naPPA) and 9 logopenic variant (lvPPA)
      cases]. RESULTS: The annualized rate of change was greater in all PPA variants in
      comparison with the AD group on the ACE-R whereas only the svPPA and naPPA groups
      differed from AD on the FRS. CONCLUSIONS: The longitudinal profile differs across
      PPA syndromes on cognitive and functional measures. Findings have theoretical
      implications and are relevant to the care of patients with dementia.

PMID- 23006976
TI  - Atrial fibrillation in aortic stenosis--echocardiographic assessment and
      prognostic importance.
AB  - BACKGROUND: Atrial fibrillation (AFib) exists more frequently in patients with
      aortic stenosis (AS) than in patients without, and AFib may be a sign of
      progressive deterioration of AS. Echocardiographic assessment of AS in sinus
      rhythm is well documented, however, little is known about AFib in AS since such
      patients often are excluded from clinical echocardiographic trials. AIM: The
      purpose of this study was to assess the prognostic importance of AFib in AS.
      METHODS: The study was designed as a single-center case-control study. Patients
      with AS and AFib were enrolled as cases (n = 103) and subsequently matched to
      controls (103 patients with AS but sinus rhythm). Cases and controls were matched
      according to age, gender and severity of AS. Primary outcome was all cause
      mortality and follow-up was 100% complete. RESULTS: Compared to controls the
      group with AFib had lower mean ejection fraction (42% vs. 49%; p < 0.001) and
      stroke volume (47 mL vs. 55 mL; p = 0.004), but higher heart rate (81 bpm vs. 68
      bpm; p < 0.001) and no significant difference with regard to cardiac output (3.8
      L vs. 4.0 L; p = 0.29). Accordingly, aortic jet velocity and gradients were
      significantly lower in AFib compared to controls but there were no differences (p
      = 0.38) in aortic valve area calculated by the continuity equation. During a
      median follow-up of 2.3 years (IQR: 1.2-3.6), 70 (34%) patients with AS died: 42
      patients with AFib and 28 patients with sinus rhythm (p < 0.02). After adjusting
      for echocardiographic significant differences, AFib remained an independent
      predictor of mortality (HR 2.72 (95% CI: 1.12-6.61), p < 0.03). There was no
      significant interaction (p = 0.62) between AFib and AS on the risk of mortality,
      indicating that AFib predicted bad outcome regardless of the severity of AS.
      CONCLUSIONS: AFib is an independent risk factor in patients with AS and the
      prognostic impact of AFib seems to be the same despite the severity of AS.

PMID- 23006978
TI  - Panax ginseng: a newly identified cause of gynecomastia.
AB  - Gynecomastia or benign proliferation of the male breast glandular tissue is not
      uncommon for adolescent males.  Its pathogenesis has been attributed to a
      transient imbalance between estrogens and androgens.  Ginseng is a popular herb
      with a long history of medicinal use.  Oriental folk medicine describes it as
      both a tonic for restoring strength and a panacea.  The term "ginseng" generally
      refers to a plant, Panax ginseng.  Based on estrogen-like actions of Panax
      ginseng due to its structural similarity with estradiol, this agent could be
      speculated to cause gynecomastia.  Here we report a 12-year-old Korean-Japanese
      boy with bilateral enlargement of the breasts with tenderness in the right
      breast, which was noticed about 1 month before his first visit to our outpatient
      clinic.  He was diagnosed with gynecomastia based on physical, laboratory, and
      ultrasound examinations.  Detailed questioning about his medications and
      supplements revealed that he had been given red ginseng extract daily to enhance
      his performance for 1 month before his clinical presentation.  He wanted to make
      his body stronger as an athlete.  He was recommended from his grandmother to take
      Panax ginseng for his purpose.  After stopping this, there was no further growth
      of the masses and no pain when his right breast was pressed.  In conclusion,
      physicians should consider ginseng in the investigation of gynecomastia.

PMID- 23006971
TI  - Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades
      which alter therapy response.
AB  - The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by
      genetic alterations in upstream signaling molecules such as receptor tyrosine
      kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5,
      PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and
      TSC2 may also be activated/inactivated by mutations or epigenetic silencing.
      Upstream mutations in one signaling pathway or even in downstream components of
      the same pathway can alter the sensitivity of the cells to certain small molecule
      inhibitors. These pathways have profound effects on proliferative, apoptotic and
      differentiation pathways. Dysregulation of components of these cascades can
      contribute to: resistance to other pathway inhibitors, chemotherapeutic drug
      resistance, premature aging as well as other diseases. This review will first
      describe these pathways and discuss how genetic mutations and epigenetic
      alterations can result in resistance to various inhibitors.

PMID- 23006979
TI  - Establishment of immortalized human amniotic mesenchymal stem cells.
AB  - Human amniotic mesenchymal cells (HAM cells) are known to contain somatic stem
      cells possessing the characteristics of pluripotency. However, little is known
      about the biology of these somatic cells because isolated HAM cells from amniotic
      membrane have a limited lifespan. To overcome  this problem, we attempted to
      prolong the lifespan of HAM cells by infecting retrovirus encoding human
      papillomavirus type16E6 and E7 (HPV16E6E7), bmi-1, and/or human telomerase
      reverse transcriptase (hTERT) genes and investigated their characteristics as
      stem cells. We confirmed the immortalization  of the four lines of cultured HAM
      cells for about 1 year. Immortalized human amnion mesenchymal cells (iHAM cells)
      have continued to proliferate over 200 population doublings (PDs). iHAM cells
      were positive for CD73, CD90, CD105, and CD44 and negative for CD34, CD14, CD45,
      and HLA-DR. They  expressed stem cell markers such as Oct3/4, Sox2, Nanog, Klf4,
      SSEA4, c-myc, vimentin, and nestin. They showed adipogenic, osteogenic, and
      chondrogenic differentiation abilities after induction. These results suggested
      that immortalized cell lines with characteristics of stem cells can be 
      established. iHAM cells with an extended lifespan can be used to produce good
      experimental models both in vitro and in vivo.

PMID- 23006980
TI  - The epidemiology of injuries in contact flag football.
AB  - OBJECTIVE: To characterize the epidemiology of injuries in post-high school male
      and female athletes in the rapidly growing international sport of contact flag
      football. DESIGN: Prospective injury-observational study. SETTING: Kraft Stadium,
      Jerusalem, Israel. PARTICIPANTS: A total of 1492 players, consisting of men (n =
      1252, mean age, 20.49 +/- 5.11) and women (n = 240, mean age, 21.32 +/- 8.95
      years), participated in 1028 games over a 2-season period (2007-2009). MAIN
      OUTCOME MEASURES: All time-loss injuries sustained in game sessions were recorded
      by the off-the-field medical personnel and followed up by a more detailed phone
      injury surveillance questionnaire. RESULTS: One hundred sixty-three injuries were
      reported, comprising 1 533 776 athletic exposures (AEs). The incidence rate was
      0.11 [95% confidence interval (CI), 0.09-0.12] per 1000 AEs, and incidence
      proportion was 10.66% (95% CI, 9.10-12.22). Seventy-six percent of the injuries
      were extrinsic in nature. Thirty percent of the injuries were to the fingers,
      thumb, and wrist, 17% to the knee, 17% to the head/face, 13% to the ankle, and
      11% to the shoulder. CONCLUSIONS: Contact flag football results in a significant
      amount of moderate to severe injuries. These data may be used in the development
      of a formal American flag football injury database and in the development and
      implementation of a high-quality, randomized, prospective injury prevention
      study. This study should include the enforcement of the no-pocket rule,
      appropriate headgear, self-fitting mouth guards, the use of ankle braces, and
      changing the blocking rules of the game.

PMID- 23006981
TI  - Brachial neuropraxia in Canadian Atlantic University sport football players: what
      is the incidence of "stingers"?
AB  - OBJECTIVES: The objectives of this study were (1) to determine the incidence of
      brachial neuropraxia (stingers) among varsity football players during the 2010
      season; (2) to determine if associations exist between sustaining a stinger and
      previous history of stingers, years played, equipment, age, body mass index
      (BMI), and conditioning; and (3) to provide descriptive statistics regarding
      stingers and position played, symptoms, activity during injury, mechanism of
      tackling, and reporting of stingers. DESIGN: Retrospective. SETTING: Canadian
      Atlantic University Sport football league. PARTICIPANTS: Two hundred forty-four
      players. ASSESSMENT OF RISK FACTORS: Two written questionnaires. MAIN OUTCOME
      MEASURES: Number of players experiencing stingers that occurred during the 2010
      season. RESULTS: The incidence was 26% (64 of 244). A multivariate analysis
      revealed that previous history of a stinger (P < 0.0001) and years played (P =
      0.0018) were associated with sustaining a stinger. There was no statistically
      significant effect related to additional equipment, a player's age, BMI, or
      participation in a strength training program. Linebackers, offensive linemen, and
      wide receivers had the highest incidence of stingers. The most frequent symptoms
      reported were tingling, numbness, burning, and weakness. Of all stingers
      sustained, only 59% (38 of 64) were reported to medical staff. CONCLUSIONS:
      Stingers are a common injury in Canadian university football and are
      underreported to medical staff. Education of players at increased risk is needed.

PMID- 23006982
TI  - Paneth cells and necrotizing enterocolitis: a novel hypothesis for disease
      pathogenesis.
AB  - Current models of necrotizing enterocolitis (NEC) propose that intraluminal
      microbes destroy intestinal mucosa and activate an inflammatory cascade that ends
      in necrosis. We suggest an alternate hypothesis wherein NEC is caused by injury
      to Paneth cells (PCs) in the intestinal crypts. PCs are specialized epithelia
      that protect intestinal stem cells from pathogens, stimulate stem cell
      differentiation, shape the intestinal microbiota, and assist in repairing the
      gut. Our novel model of NEC uses neonatal mice and ablates PCs followed by
      enteral infection. We contrast this model with other animal examples of NEC and
      the clinical disease. Selective destruction of PCs using dithizone likely
      releases tumor necrosis factor-alpha and other inflammatory mediators. We propose
      that this event produces inflammation in the submucosa, generates platelet
      activating factor, and induces a coagulopathy. The role of PCs in NEC is
      consistent with the onset of disease in preterm infants after a period of PC
      related maturation, the central role of PCs in crypt-related homeostasis, the
      anatomic location of pneumatosis intestinalis close to the crypts, and the
      proximity of PCs to occluded blood vessels that cause coagulation necrosis of the
      intestinal villi. We offer this hypothesis to promote new thoughts about how NEC
      occurs and its potential prevention.

PMID- 23006983
TI  - An outcome measure of functionality in patients with lumber spinal stenosis: a
      validation study of the Iranian version of Neurogenic Claudication Outcome Score
      (NCOS).
AB  - BACKGROUND: Neurogenic claudication (NC) is a common symptom in patients with
      lumbar spinal stenosis (LSS). The Neurogenic Claudication Outcome Score (NCOS) is
      a very short instrument for measuring functional status in these patients. This
      study aimed to translate and validate the NCOS in Iran. METHODS: This was a
      prospective clinical validation study. The 'forward-backward' procedure was
      applied to translate the NCOS from English into Persian (Iranian language). A
      total of 84 patients with NC were asked to respond to the questionnaire at two
      points in time: at preoperative and at postoperative (6 months follow-up)
      assessments. The Oswestry Disabiltiy Index (ODI) also was completed for patients.
      To test reliability, the internal consistency was assessed by Cronbach's alpha
      coefficient. Validity was evaluated using known groups comparison and criterion
      validity (convergent validity). Internal responsiveness of the NCOS to the
      clinical intervention (surgery) also was assessed comparing patients' pre- and
      postoperative scores. RESULTS: The Cronbach's alpha coefficients for the NCOS at
      preoperative and postoperative assessments were 0.77 and 0.91, respectively.
      Known groups analysis showed satisfactory results. The instrument discriminated
      well between sub-groups of patients who differed in claudication distance as
      measured by the Self-Paced Walking Test (SPWT). The change in the ODI after
      surgery was strongly correlated with change in the NCOS, lending support to its
      good convergent validity (r = 0.81; P < 0.001). Further analysis also indicated
      that the questionnaire was responsive to the clinical intervention (surgery) as
      expected (P < 0.0001). CONCLUSION: In general, the Iranian version of the NCOS
      performed well and the findings suggest that it is a reliable and valid measure
      of functionality in patients with lumbar spinal stenosis who are suffering from
      neurogenic claudication.

PMID- 23006984
TI  - Targeting Rho associated kinases in leukemia and myeloproliferative neoplasms.
AB  - If ROCKs are going to be targeted as anti-leukemic agents either as a monotherapy
      or in combination with existing drugs, a better characterization of the relative
      contribution of ROCK1 and ROCK2 in disease progression is essential.

PMID- 23006985
TI  - Maternal obesity affects gene expression and cellular development in fetal
      brains.
AB  - OBJECTIVES: Female rat neonates reared on a high carbohydrate (HC) milk formula
      developed chronic hyperinsulinemia and adult-onset obesity (HC phenotype).
      Furthermore, we have shown that fetal development in the HC intrauterine
      environment (maternal obesity complicated with hyperinsulinemia, hyperleptinemia,
      and increased levels of proinflammatory markers) resulted in increased levels of
      serum insulin and leptin in term HC fetuses and the spontaneous transfer of the
      HC phenotype to the adult offspring. The objectives of this study are to identify
      changes in global gene expression pattern and cellular development in term HC
      fetal brains in response to growth in the adverse intrauterine environment of the
      obese HC female rat. METHODS: GeneChip analysis was performed on total RNA
      obtained from fetal brains for global gene expression studies and
      immunohistochemical analysis was performed on fetal brain slices for
      investigation of cellular development in term HC fetal brains. RESULTS: Gene
      expression profiling identified changes in several clusters of genes that could
      contribute to the transfer of the maternal phenotype (chronic hyperinsulinemia
      and adult-onset obesity) to the HC offspring. Immunohistochemical analysis
      indicated diminished proliferation and neuronal maturation of stem-like cells
      lining the third ventricle, hypothalamic region, and the cerebral cortex in HC
      fetal brains. DISCUSSION: These results suggest that maternal obesity during
      pregnancy could alter the developmental program of specific fetal brain cell
      networks. These defects could underlie pathologies such as metabolic syndrome and
      possibly some neurological disorders in the offspring at a later age.

PMID- 23006986
TI  - Longitudinal neuroimaging and neuropsychological profiles of frontotemporal
      dementia with C9ORF72 expansions.
AB  - INTRODUCTION: Frontotemporal dementia (FTD) is a common cause of early-onset
      dementia with a significant genetic component, as underlined by the recent
      identification of repeat expansions in the gene C9ORF72 as a major cause of FTD
      and motor neuron disease. Understanding the neurobiology and clinical
      phenomenology of this novel mutation is currently a major research focus.
      However, few data are available concerning the longitudinal evolution of this
      genetic disease. Here we present longitudinal neuropsychological and neuroimaging
      data on a cohort of patients with pathological repeat expansions in C9ORF72.
      METHODS: Following a review of the University College London FTD DNA database, 20
      cases were retrospectively identified with a C9ORF72 expansion. Twelve cases had
      longitudinal neuropsychology data available and six of these cases also had
      longitudinal volumetric brain magnetic resonance imaging. Cortical and
      subcortical volumes were extracted using FreeSurfer. Rates of whole brain,
      hemispheric, cerebellar and ventricular change were calculated for each subject.
      Nonlinear fluid registration of follow-up to baseline scan was performed to
      visualise longitudinal intra-subject patterns of brain atrophy and ventricular
      expansion. RESULTS: Patients had low average verbal and performance IQ at
      baseline that became impaired (< 5th percentile) at follow-up. In particular,
      visual memory, naming and dominant parietal skills all showed deterioration. Mean
      rates of whole brain atrophy (1.4%/year) and ventricular expansion (3.2 ml/year)
      were substantially greater in patients with the C9ORF72 mutation than in healthy
      controls; atrophy was symmetrical between the cerebral hemispheres within the
      C9ORF72 mutation group. The thalamus and cerebellum showed significant atrophy
      whereas no cortical areas were preferentially affected. Longitudinal fluid
      imaging in individual patients demonstrated heterogeneous patterns of progressive
      volume loss; however, ventricular expansion and cerebellar volume loss were
      consistent findings. CONCLUSION: Disease evolution in C9ORF72-associated FTD is
      linked neuropsychologically with increasing involvement of parietal and amnestic
      functions, and neuroanatomically with rather diffuse and variable cortical and
      central atrophy but more consistent involvement of the cerebellum and thalamus.
      These longitudinal profiles are consistent with disease spread within a
      distributed subcortical network and demonstrate the feasibility of longitudinal
      biomarkers for tracking the evolution of the C9ORF72 mutation phenotype.

PMID- 23006987
TI  - Research progress in the radioprotective effect of superoxide dismutase.
AB  - Irradiation from diverse sources is ubiquitous and closely associated with human
      activity. Radiation therapy (RT), an important component of the multiple
      radiation origins, contributes significantly to oncotherapy by killing tumor
      cells. On the other hand, RT can also cause some undesired normal tissue injuries
      that afflict numerous cancer patients. Although many promising radioprotective
      agents are emerging, few of them have entered the market successfully due to
      various limitations. At present, the most accepted hypothesis for the radiation
      caused injury involves reactive oxygen species (ROS) generation. Superoxide
      dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide
      radicals, is expected to occupy an indispensable position in the treatment of ROS
      mediated tissue injuries originating from exposure to radiation. This review
      focuses on the mechanism of radioprotection by SOD at the tissue or organ level,
      cellular level, and molecular level, respectively, in order to provide references
      for further investigation of radiation injury and development of new
      radioprotectors.

PMID- 23006988
TI  - An overview on antiepileptic drugs.
AB  - Epilepsy is the most common chronic neurological disorder of the brain. For
      several decades different kinds of medications have been used to treat epilepsy.
      Even though many surgical advances has been made and implemented, medications
      remain the basis of treatment. The search for noble antiepileptic drugs (AEDs)
      with more selective activity and lower toxicity continues to be an area of
      intensive investigation in medicinal chemistry. Additionally, drug resistance is
      an important clinical problem in epilepsy and is associated with an increased
      risk of morbidity and mortality. This review intends to present a comprehensive
      overview on AED in particular along with discussion on some aspects of associated
      drug resistance and combination therapy.

PMID- 23006989
TI  - Anti-inflammatory activities of fractions from Geranium nepalense and related
      polyphenols.
AB  - Geranium nepalense Sweet is a common Chinese herbal medicine and has been used as
      influenza, dysentery, antiphlogistic and analgesic tonic, hemostatic, stomachic,
      and antidiabetic drugs. The anti-inflammatory effects of G. nepalense on
      tetradecanoyl phorbol acetate (TPA)-induced mouse ear edema were studied in this
      work. The results showed that ethyl acetate fraction of the water extract of G.
      nepalense possessed significant activity at 2.5 g/kg (p < 0.01) with aspirin as a
      positive control (0.6 g/kg). Six polyphenolic compounds, including three
      flavonoids, i.e. kaempferol, kaempferol-7-O-beta-D-glucopyranoside, and quercetin
      7-O-alpha-rhamnopyranoside, and two tannins, i.e. pyrogallol and gallic acid, and
      one lignin, i.e. epipinoresinol, were isolated and characterized from ethyl
      acetate fraction. The isolation of polyphenols provides a clue for beneficial
      effects of G. nepalense in the demonstrated anti-inflammatory activity.

PMID- 23006990
TI  - Synthesis and structure-activity relationship study of 2-(substituted
      benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)
      one derivatives as anticancer agents.
AB  - The synthesis and structure-activity relationship (SAR) study of a series of 2
      (substituted benzylidene)-7-(4-fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2
      a]pyrimidin-3(7H)-one (4a-4j) derivatives as anticancer agents are described.
      This series of thiazolopyrimidines were synthesized by the reaction of 7-(4
      fluoro phenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a] pyrimidin-3(7H)-one (3) with
      appropriate substituted aldehydes in the presence of anhydrous sodium acetate and
      glacial acetic acid. Their structures were confirmed by IR, (1)H-NMR, mass, and
      elemental analyses. These novel thiazolopyrimidine derivatives were screened for
      their anticancer activity on the U937 human histocytic lymphoma cell line by 3
      (4,5-dimethyl thiazole-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. The
      comparison of anticancer activity of thiazolopyrimidine was performed considering
      their structures. This study was done using 2-(substituted benzylidene)-7-(4
      fluorophenyl)-5-(furan-2-yl)-2H-thiazolo[3,2-a]pyrimidin-3(7H)-one (4a-4j) as a
      basic model, showing that i) presence of a hydrogen donor/acceptor domain
      [thiazolo[3,2-a]pyrimidin-3(7H)-one] on the thiazolopyrimidine ring; ii) presence
      of a hydrophobic [(4-fluorophenyl)] aryl ring system on the thiazolopyrimidine
      ring; iii) presence of an electron donor moiety [5-(furan-2-yl)] on the
      thiazolopyrimidine ring; iv) ortho and para substitution of the distal aryl ring
      [2-(substituted benzylidene)] function strongly influenced anticancer activity.
      Among these compounds (4a-4j) para substituted derivatives 4c, 4e, 4f, 4g, 4h,
      and 4j showed significant anticancer activity.

PMID- 23006991
TI  - Antioxidant and hepatoprotective activity of an ethanol extract of Syzygium
      jambos (L.) leaves.
AB  - Herbal medicines have traditionally been used worldwide for the prevention and
      treatment of liver disease with fewer adverse effects. The leaves of the Syzygium
      jambos (SJL) plant were chosen and studied for their antioxidant activity in
      vitro and hepatoprotective activity in vivo. The antioxidant activity of the
      ethanol extract was examined in vitro using a 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) free radical scavenging assay, reducing capacity, total phenol, total
      flavonoid content, and total antioxidant capacity. The extract had significant
      dose-dependent antioxidant activity in all in vitro experiments. IC(50) values of
      SJL and ascorbic acid (standard) were found to be 14.10 and 4.87 MUg/mL,
      respectively, according to a DPPH radical scavenging assay. Hepatoprotective
      activity of the plant extract was evaluated in a rat model of carbon
      tetrachloride (CCl(4))-induced liver damage. CCl(4) significantly altered serum
      marker enzymes, total bilirubin, total protein, and liver weight. The extract
      caused these values to return to normal in rats with CCl(4)-induced liver damage
      that were given SJL. This indicated the hepatoprotective potential of SJL and was
      comparable to use of the standard drug silymarin. Thus, the present study
      revealed that SJL may have antioxidant and hepatoprotective activity.

PMID- 23006992
TI  - Antimicrobial screening of some Egyptian plants and active flavones from
      Lagerstroemia indica leaves.
AB  - One hundred and twenty four plant extracts were evaluated for their antimicrobial
      activity against four pathogenic bacteria (Staphylococcus aureus (ATCC 8095),
      Salmonella enteritides (ATCC 13076), Escherichia coli (ATCC 25922), and Listeria
      monocytogenes (ATCC 15313)) and Candida albicans yeast (ATCC 10231) using the
      disk diffusion and broth microdilution methods. Of the plant extracts, fourteen
      exhibited antimicrobial activity against two or more of the five microorganisms
      tested. Only the methanol extract of Lagerstroemia indica leaves exhibited
      antimicrobial activity against all pathogenic bacteria and C. albicans yeast that
      were tested. Purification of the methanol extract of L. indica leaves using
      antimicrobial assay-guided isolation yielded one pure active compound. The
      chemical structure of the isolated active compound was found to be '4-methoxy
      apigenin-8-C-beta-D-glucopyranoside; cytisoside according to detailed
      spectroscopic analysis of its nuclear magnetic resonance and mass spectrometry
      data. The compound exhibited antimicrobial activity against C. albicans (minimum
      lethal concentration (MLC): 32 MUg/mL), S. aureus (MLC: 16 MUg/mL), S.
      enteritides (MLC: 16 MUg/mL), E. coli (MLC: 16 MUg/mL), and L. monocytogenes
      (MLC: 16 MUg/mL). The present study found that the methanol extract of L. indica
      leaves holds great promise as a potential source of beneficial antimicrobial
      components for different applications.

PMID- 23006993
TI  - Optimization of cell-wall skeleton derived from Mycobacterium bovis BCG Tokyo 172
      (SMP-105) emulsion in delayed-type hypersensitivity and antitumor models.
AB  - Cell-wall skeleton prepared from Mycobacterium bovis BCG (BCG-CWS) is known as a
      potent adjuvant and has been shown to possess antitumor activity in many non
      clinical and clinical studies. As there are no approved BCG-CWS formulations for
      cancer therapy, we investigated the potential for cancer immunotherapy of SMP
      105, our originally produced BCG-CWS. For optimizing SMP-105 emulsion, we
      compared the effects of drakeoland squalane-based SMP-105 emulsions on IFN-gamma
      production in rats and evaluated their ability to induce skin reaction in guinea
      pigs. Both emulsions had the same activity in both experiments. We selected
      squalane as base material and produced two types of squalane-based formulations
      (vialed emulsion and pumped emulsion) that can easily be prepared as oil-in-water
      emulsions. Although the vialed emulsion showed the same pattern of distribution
      as a usual homogenized emulsion, the pumped emulsion showed more uniform
      distribution than the other two emulsions. Whereas both emulsions enhanced strong
      delayed type hypersensitivity (DTH) reaction in a mouse model, the pumped
      emulsion induced slightly smaller edema. Data on oil droplet size distribution
      suggest that few micrometer oil droplet size might be appropriate for oil-in
      water microemulsion of SMP-105. The antitumor potency of SMP-105 emulsion was
      stronger than that of some of the launched toll-like receptor (TLR) agonists
      (Aldara cream, Picibanil, and Immunobladder). Aldara and Picibanil showed limited
      antitumor effectiveness, while Immunobladder had almost the same effect as SMP
      105 at the highest dose, but needed about 10 times the amount of SMP-105. These
      findings first indicate that SMP-105 has great potential in cancer immunotherapy.

PMID- 23006994
TI  - Animal welfare and use of silkworm as a model animal.
AB  - Sacrificing model animals is required for developing effective drugs before being
      used in human beings. In Japan today, at least 4,210,000 mice and other mammals
      are sacrificed to a total of 6,140,000 per year for the purpose of medical
      studies. All the animals treated in Japan, including test animals, are managed
      under control of "Act on Welfare and Management of Animals". Under the principle
      of this Act, no person shall kill, injure, or inflict cruelty on animals without
      due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal".
      If we can make use of invertebrate animals in testing instead of vertebrate ones,
      that would be a remarkable solution for the issue of animal welfare. Furthermore,
      there are numerous advantages of using invertebrate animal models: less space and
      small equipment are enough for taking care of a large number of animals and thus
      are cost-effective, they can be easily handled, and many biological processes and
      genes are conserved between mammals and invertebrates. Today, many invertebrates
      have been used as animal models, but silkworms have many beneficial traits
      compared to mammals as well as other insects. In a Genome Pharmaceutical
      Institute's study, we were able to achieve a lot making use of silkworms as model
      animals. We would like to suggest that pharmaceutical companies and institutes
      consider the use of the silkworm as a model animal which is efficacious both for
      financial value by cost cutting and ethical aspects in animals' welfare.

PMID- 23006995
TI  - Repeated intravitreal dexamethasone implant (Ozurdex(r)) for retinal vein
      occlusion.
AB  - PURPOSE: To evaluate the effects of repeated intravitreal dexamethasone implant
      (IDI) (Ozurdex(r)) in eyes with macular edema (ME) due to retinal vein occlusion
      (RVO). METHODS: We reviewed the charts of patients with RVO-related ME, who
      received repeated Ozurdex IDI (0.7 mg) on an 'as-needed' basis. Main outcome
      measures included changes in best-corrected visual acuity (BCVA), central macular
      thickness (CMT), retreatment interval, and incidence of side effects. RESULTS: A
      total of 33 eyes were included for analysis. Retreatment with Ozurdex was judged
      necessary after 4.7 +/- 1.1 months from the first IDI (1st IDI) and 5.1 +/- 1.5
      months from the second IDI (2nd IDI). Baseline BCVA was 0.65 +/- 0.43 logMAR; it
      significantly improved to 0.50 +/- 0.42 logMAR after 1.4 +/- 0.7 months from the
      1st IDI (peaking efficacy) (p < 0.001) and to 0.48 +/- 0.44 logMAR after 1.8 +/-
      0.8 months from the 2nd IDI (peaking efficacy) (p < 0.001). CMT decreased from
      636 +/- 217 um (baseline) to 300 +/- 114 um, 1.4 +/- 0.7 months after the 1st IDI
      (p < 0.001), and to 298 +/- 91 um, 1.8 +/- 0.8 months after the 2nd IDI (p <
      0.001). A rebound effect was recorded in 7 eyes after the 1st IDI (mean 168 +/-
      158 um) and in 4 eyes after the 2nd IDI (mean 215 +/- 199 um). All eyes with a
      rebound effect improved again after a 2nd intravitreal Ozurdex injection. No
      serious adverse events were observed; 12 eyes developed a transient IOP increase,
      and cataracts were extracted in 2 eyes. CONCLUSION: Repeated intravitreal Ozurdex
      on an 'as-needed' basis, with a retreatment interval <6 months, may produce long
      term clinically meaningful benefits in the treatment of ME due to RVO, without
      other significant side effects than expected after intraocular corticosteroid
      treatment.

PMID- 23006996
TI  - Acute multivessel coronary artery occlusion: a case report.
AB  - BACKGROUND: In terms of clinical and angiographic findings, multiple simultaneous
      coronary occlusions in acute myocardial infarction are infrequent, and the
      mechanism of the occlusions is unclear. CASE PRESENTATION: We herein report a
      rare case of two simultaneously occluded coronary arteries, one of which
      subsequently underwent spontaneous lysis. An 88-year-old man had a 3-hour attack
      of acute crushing retrosternal chest pain. His first electrocardiogram showed ST
      segment elevation in the inferior (II, III, and aVF) and anterior (V3-V6) leads.
      His second electrocardiogram in the cardiac care unit showed ST-segment elevation
      in the inferior leads but ST-segment depression in the anterior leads. Emergency
      coronary angiography revealed that the right coronary artery was acutely and
      totally occluded at the midportion and that the proximal and midportion of the
      left anterior descending coronary artery had an acute thrombus. According to his
      electrocardiogram and coronary angiography findings, we inferred that the right
      coronary artery and left anterior descending coronary artery first totally
      occluded simultaneously, and then the thrombus in the left anterior descending
      coronary artery spontaneously underwent partial lysis. Therefore, intervention of
      the right coronary artery was performed followed by injection of glycoprotein IIB
      IIIA inhibitor into the left anterior descending coronary artery. He had an
      uneventful hospital course and was discharged home 10 days later. CONCLUSION:
      Because patients with multivessel coronary artery occlusion are often in serious
      condition, abnormal electrocardiographic results must be identified and affected
      vessel should be opened timely and efficiently to save the myocardium and reduce
      complications such as congestive heart failure.

PMID- 23006998
TI  - A new approach to the drug release kinetics of a discrete system: SiO2 system
      obtained by ultrasonic dry spraying.
AB  - Mesoporous silica materials have already proved to be non-toxic and
      biocompatible, and also to have large pore volume and very high specific surface
      area suitable for loading of small molecules. Having this in mind and the fact
      that silicon dioxide (SiO(2)) powders can be so designed to obtain particle
      structures organized at multi levels, SiO(2) was chosen as a potential carrier
      for metronidazole, an antibiotic drug. SiO(2) powder was synthesized in two
      stages: first silica sol was prepared by hydrothermal synthesis and second the
      sol was converted into powder by dry spraying with simultaneous incorporation of
      the antibiotic into its structure. Scanning and transmission electron microscopy
      study revealed very complex structure and sub-structure of SiO(2) particles. Cell
      viability tests were used for estimation of cytotoxicity of so synthesized
      SiO(2). The drug release data showed that the system can provide drug release for
      a long time. Also, the device behavior is fully predictable, according to our
      theoretical model of multilevel structure design, and gives many opportunities
      for model investigations of drug release and its kinetics. The pore sizes and
      their distribution were observed as a limiting factor of drug release kinetics.
      Therefore, as the pore sizes are given as a set of discrete values, the kinetics
      of drug release might also be given as a set of corresponding discrete values.

PMID- 23006997
TI  - Improving patient-centeredness of fertility care using a multifaceted approach:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Beside traditional outcomes of safety and (cost-)effectiveness, the
      Institute of Medicine states patient-centeredness as an independent outcome
      indicator to evaluate the quality of healthcare. Providing patient-centered care
      is important because patients want to be heard for their ideas and concerns.
      Healthcare areas associated with high emotions and intensive treatment periods
      could especially benefit from patient-centered care. How care can become
      optimally improved in patient-centeredness is unknown. Therefore, we will conduct
      a study in the context of Dutch fertility care to determine the effects of a
      multifaceted approach on patient-centeredness, patients' quality of life (QoL)
      and levels of distress. Our aims are to investigate the effectiveness of a
      multifaceted approach and to identify determinants of a change in the level of
      patient-centeredness, patients' QoL and distress levels. This paper presents the
      study protocol. METHODS/DESIGN: In a cluster-randomized trial in 32 Dutch
      fertility clinics the effects of a multifaceted approach will be determined on
      the level of patient-centeredness (Patient-centredness Questionnaire -
      Infertility), patients' QoL (FertiQoL) and levels of distress (SCREENIVF). The
      multifaceted approach includes audit and feedback, educational outreach visits
      and patient-mediated interventions. Potential determinants of a change in patient
      centeredness, patients' QoL and levels of distress will be collected by an
      addendum to the patients' questionnaire and a professionals' questionnaire. The
      latter includes the Organizational Culture Assessment Instrument about the
      clinic's culture as a possible determinant of an increase in patient-centered
      care. DISCUSSION: The study is expected to yield important new evidence about the
      effects of a multifaceted approach on levels of patient-centeredness, patients'
      QoL and distress in fertility care. Furthermore, determinants associated with a
      change in these outcome measures will be studied. With knowledge of these
      results, patient-centered care and thus the quality of healthcare can be
      improved. Moreover, the results of this study could be useful for similar
      initiatives to improve the quality of care delivery. The results of this project
      are expected at the end of 2013. TRIAL REGISTRATION: Clinicialtrials.gov
      NCT01481064.

PMID- 23006999
TI  - Tyrosine phosphorylation of a SNARE protein, syntaxin 17: implications for
      membrane trafficking in the early secretory pathway.
AB  - The T-cell protein tyrosine phosphatase is expressed as two splice variants -
      TC45, a nuclear protein, and TC48, which is localized predominantly in the ER
      (endoplasmic reticulum). Yeast two-hybrid screening revealed direct interaction
      of TC48 with Syntaxin17, a SNARE (soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor) protein localized predominantly in the ER and to
      some extent in the ER-Golgi intermediate compartment. Syntaxin 17 did not
      interact with TC45. C-terminal 40 amino acids of TC48 were sufficient for
      interaction with syntaxin 17. Overexpressed syntaxin 17 was phosphorylated at
      tyrosine upon pervanadate treatment (a tyrosine phosphatase inhibitor/tyrosine
      kinase activator) of COS-1 cells. Mutational analysis identified Tyr156 in the
      cytoplasmic domain as the major site of phosphorylation. Endogenous syntaxin 17
      was phosphorylated by pervanadate treatment in CHO and MIN6 cells but was not
      phosphorylated in a variety of other cell lines tested. c-Abl was identified as
      one of the kinases, which phosphorylates syntaxin 17 in MIN6 cells.
      Phosphorylation of endogenous and overexpressed syntaxin 17 was reduced in the
      presence of IGF receptor and EGF receptor kinase inhibitors. Serum depletion
      reduced pervanadate-induced phosphorylation of endogenous syntaxin 17. TC48
      coexpression reduced phosphorylation of syntaxin 17 by pervanadate and purified
      TC48 directly dephosphorylated syntaxin 17. beta-COP dispersal by overexpressed
      syntaxin 17 was reduced after pervanadate-induced phosphorylation. A phospho
      mimicking mutant (Y156E) of syntaxin 17 showed reduced interaction with COPI
      vesicles. These results suggest that tyrosine phosphorylation of syntaxin 17 is
      likely to have a role in regulating syntaxin 17 dependent membrane trafficking in
      the early secretory pathway.

PMID- 23007003
TI  - The effectiveness of current acute variceal bleed treatments in unselected
      cirrhotic patients: refining short-term prognosis and risk factors.
AB  - OBJECTIVES: The mortality from esophageal variceal hemorrhage in liver cirrhosis
      patients remains approximately 15-20%. Predictors of short-term outcomes, such as
      the hepatic venous pressure gradient, are often unavailable in the acute setting.
      Clinical variables seem to have a similar predictive performance, but some
      variables including active bleeding during endoscopy have not been reevaluated
      after the utilization of endoscopic banding as endoscopic procedure. In addition,
      patients with severe liver failure are often excluded from clinical trials. The
      aim of this study was to prospectively reevaluate the risk factors affecting a 5
      day failure after acute variceal bleeding in unselected cirrhotic patients,
      managed with the current standard treatment using vasoactive drugs, band
      ligation, and antibiotics. METHODS: One hundred and eighty five patients with
      liver cirrhosis and variceal bleeding admitted from January 2010 to July 2011
      were evaluated. RESULTS: Hepatocellular carcinoma was present in 28.1% of cases
      and portal vein thrombosis (PVT) was present in 17.3% of cases. Band ligation was
      feasible in 92.4% of cases. Five-day failure occurred in 16.8% of cases; 12
      patients (6.5%) experienced failure to control bleeding or early rebleeding, and
      66.7% of patients died within 5 days. The overall 5-day mortality rate was 14.6%.
      By multivariate analysis, we determined that Child-Pugh class C, a white blood
      cell count over 10 * 10(9)/l, and the presence of PVT were the only independent
      predictors of the 5-day failure. CONCLUSIONS: The prognosis of a consistent group
      of liver cirrhosis patients with variceal bleeding remains poor. The current
      treatment is highly effective in controlling variceal bleeding, but mortality is
      related mainly to the severity of liver failure.

PMID- 23007004
TI  - Esophageal stasis on a timed barium esophagogram predicts recurrent symptoms in
      patients with long-standing achalasia.
AB  - OBJECTIVES: In achalasia, early recognition of the need for retreatment is of
      crucial importance to reduce morbidity and long-term complications such as
      esophageal decompensation. In clinical practice, symptoms and parameters of
      esophageal function including lower esophageal sphincter (LES) pressure and
      esophageal emptying are used to decide whether additional treatment is required.
      However, which of these tests performs best remains unclear. METHODS: A cohort of
      41 patients with long-standing achalasia (median 17 years), underwent esophageal
      manometry, timed barium esophagogram and symptom evaluation. Patients were
      followed up for 10 years, and were regarded as a therapeutic failure if Eckardt
      score was >3 or when retreatment was needed. Predictors of therapeutic failure
      were evaluated. RESULTS: Of the 41 included patients, 7 patients had an elevated
      LES pressure (>10 mm Hg) and 26 had esophageal stasis >5 cm on timed barium
      esophagogram. During follow-up, 25 patients had recurrence of symptoms and were
      considered therapeutic failures. Of the 25 patients, 5 had an elevated LES
      pressure, whereas 22 had esophageal stasis on barium esophagogram. Hence, the
      sensitivity to predict the need of retreatment is higher for esophageal stasis
      (88%) compared with LES pressure (20%). A total of 16 patients (39%) were in long
      term remission, of which 12 patients (75%) did not have stasis at their initial
      visit. CONCLUSIONS: In contrast to LES pressure, esophageal stasis is a good
      predictor of treatment failure in patients with long-standing achalasia. Based on
      these findings, we propose to use timed barium esophagogram rather than
      esophageal manometry as test to decide on retreatment.

PMID- 23007005
TI  - Evaluation of mucosal healing of ulcerative colitis by a quantitative fecal
      immunochemical test.
AB  - OBJECTIVES: Accumulating evidence has underlined the importance of mucosal
      healing as a treatment goal for ulcerative colitis (UC). Quantitative fecal
      immunochemical tests (FITs), which can rapidly quantify fecal blood with
      automated equipment, have been used recently to screen for colorectal neoplasia.
      The aim of this study is to determine whether an FIT can evaluate mucosal healing
      in UC. METHODS: Feces collected from UC patients who underwent colonoscopy were
      examined by FITs, and results were compared with colonoscopic findings. Mucosal
      status was assessed using the Mayo endoscopic subscore classification. Maximum
      score for the colorectum in each patient was recorded. RESULTS: Evaluated were
      FIT results in conjunction with 310 colonoscopies that were performed in 152 UC
      patients. A large majority of patients with a Mayo 0 endoscopic score had
      negative FIT (<100 ng/ml) results (92%), and the proportion of negative FIT
      results decreased with increases in the Mayo score (Mayo 1: 47%, Mayo 2: 13%,
      Mayo 3: 12%, P<0.0001, Cochran-Armitage trend test). When the negative FIT was
      defined as <100 ng/ml, the sensitivity and specificity of a negative FIT for
      mucosal healing (Mayo 0) were 0.92 and 0.71, respectively. When mucosal healing
      was defined as Mayo 0 or 1, those were 0.60 and 0.87, respectively. In addition,
      a positive FIT (>=100 ng/ml) predicted mucosal inflammation (Mayo 2 or 3) with
      sensitivity 0.87 and specificity 0.60, respectively. CONCLUSIONS: The FIT can
      effectively and noninvasively evaluate mucosal healing in UC. This easy, rapid
      method can help evaluate and control disease activity of UC.

PMID- 23007007
TI  - Why do patients engage in medical tourism?
AB  - Medical tourism is commonly perceived and popularly depicted as an economic
      issue, both at the system and individual levels. The decision to engage in
      medical tourism, however, is more complex, driven by patients' unmet need, the
      nature of services sought and the manner by which treatment is accessed. In order
      to beneficially employ the opportunities medical tourism offers, and address and
      contain possible threats and harms, an informed decision is crucial. This paper
      aims to enhance the current knowledge on medical tourism by isolating the focal
      content of the decisions that patients make. Based on the existing literature, it
      proposes a sequential decision-making process in opting for or against medical
      care abroad, and engaging in medical tourism, including considerations of the
      required treatments, location of treatment, and quality and safety issues
      attendant to seeking care. Accordingly, it comments on the imperative of access
      to health information and the current regulatory environment which impact on this
      increasingly popular and complex form of accessing and providing medical care.

PMID- 23007006
TI  - Marital status, health and mortality.
AB  - Marital status and living arrangements, along with changes in these in mid-life
      and older ages, have implications for an individual's health and mortality.
      Literature on health and mortality by marital status has consistently identified
      that unmarried individuals generally report poorer health and have a higher
      mortality risk than their married counterparts, with men being particularly
      affected in this respect. With evidence of increasing changes in partnership and
      living arrangements in older ages, with rising divorce amongst younger cohorts
      offsetting the lower risk of widowhood, it is important to consider the
      implications of such changes for health in later life. Within research which has
      examined changes in marital status and living arrangements in later life a key
      distinction has been between work using cross-sectional data and that which has
      used longitudinal data. In this context, two key debates have been the focus of
      research; firstly, research pointing to a possible selection of less healthy
      individuals into singlehood, separation or divorce, while the second debate
      relates to the extent to which an individual's transitions earlier in the life
      course in terms of marital status and living arrangements have a differential
      impact on their health and mortality compared with transitions over shorter time
      periods. After reviewing the relevant literature, this paper argues that in order
      to fully account for changes in living arrangements as a determinant of health
      and mortality transitions, future research will increasingly need to consider a
      longer perspective and take into account transitions in living arrangements
      throughout an individual's life course rather than simply focussing at one stage
      of the life course.

PMID- 23007008
TI  - Goal setting during rehabilitation early and late after acquired brain injury.
AB  - PURPOSE OF REVIEW: Goal setting in one format or another is used by most acute,
      post-acute and community rehabilitation teams. However, the contribution that
      goal setting makes to the rehabilitation process is not yet established.
      Similarly, the specific form of goal setting that is most useful is still to be
      determined. The purpose of this review was to examine recent studies of goal
      setting and identify implications for clinical practice both early and late after
      brain injury. RECENT FINDINGS: Increasing patient involvement in the goal-setting
      process is feasible without significant additional resource, improves the patient
      experience of rehabilitation, and changes the nature of goals set to goals that
      are more meaningful to individuals without loss of levels of overall goal
      achievement. There is preliminary evidence that reminding technology can enhance
      learning of goals in both inpatient and outpatient rehabilitation. Goal
      attainment scaling offers a means of measuring outcome in complex,
      multidisciplinary rehabilitation programmes. Its sensitivity to change may be
      increased by adoption of a six-point grading scale, but questions have been
      raised concerning its reliability as a tool for use in randomised controlled
      trials. SUMMARY: Goal setting is not just an administrative tool, it is a
      clinical intervention. Rehabilitation team members should question whether
      practice within their own service is optimal and in particular the extent to
      which their current goal setting practice genuinely involves, wherever possible,
      patients as collaborative partners. Provision of support to participate in goal
      setting as well as to remember goals and use goal progress feedback may be
      necessary.

PMID- 23007009
TI  - Epidermal growth factor receptor:  a re-emerging target in glioblastoma.
AB  - PURPOSE OF REVIEW: Amplification and overexpression of the epidermal growth
      factor receptor (EGFR) gene are a hallmark of primary glioblastoma (45%), making
      it a prime target for therapy. In addition, these amplifications are frequently
      associated with oncogenic mutations in the extracellular domain. However, efforts
      at targeting the EGFR tyrosine kinase using small molecule inhibitors or
      antibodies have shown disappointing efficacy in clinical trials for newly
      diagnosed or recurrent glioblastoma. Here, we review recent insights into
      molecular mechanisms relevant for effective targeting of the EGFR pathway. RECENT
      FINDINGS: Molecular workup of glioblastoma tissue of patients under treatment
      with small molecule inhibitors has established drug concentrations in the tumor
      tissue, and has shed light on the effectiveness of target inhibition and
      respective effects on pathway signaling. Further, functional analyses of
      interaction of small molecule inhibitors with distinct properties to bind to the
      active or inactive form of EGFR have provided new insights that will impact the
      choice of drugs. Finally, vaccination approaches targeting the EGFRvIII mutant
      featuring a tumor-specific antigen have shown promising results that warrant
      larger controlled clinical trials. SUMMARY: A combination of preclinical and
      clinical studies at the molecular level has provided new insights that will allow
      refining strategies for targeting the EGFR pathway in glioblastoma.

PMID- 23007010
TI  - Endpoints for clinical trials and revised assessment in neuro-oncology.
AB  - PURPOSE OF REVIEW: Recent advances in survival for patients with newly diagnosed
      and recurrent brain tumors, combined with the development of an ever-increasing
      number of potential treatments, has led to significant growth in the number of
      clinical trials for patients with brain tumors. Suitable clinical trial design
      and endpoints are vital for successfully evaluating these new treatments that may
      continue to improve outcome. However, inadequacies of clinical trial endpoints
      have challenged how best to evaluate promising new therapeutics. RECENT FINDINGS:
      Pseudoprogression and pseudoresponse confound imaging-based endpoints, including
      overall radiographic response and progression-free survival. Overall survival is
      still regarded as the definitive endpoint, but recently identified active salvage
      agents such as bevacizumab may diminish the association between presalvage
      therapy and overall survival, making interpretation of clinical trial results
      difficult. Novel imaging and the assessment of patient function, quality of life
      (QOL), and cognition are more frequently employed as endpoints. SUMMARY: An
      awareness of the benefits and imperfections of clinical trial endpoints will lead
      to improved clinical trial design and results. Validated endpoints of patient
      function, QOL, and cognition are available and increasingly valued as secondary
      endpoints.

PMID- 23007011
TI  - Molecular approaches to ependymoma:  the next step(s).
AB  - PURPOSE OF REVIEW: Effective treatment options for ependymoma apart from radical
      surgery and radiotherapy remain scarce, and the understanding of the molecular
      basis of ependymoma biology is crucial to the development of novel therapies.
      Comprehensive work revealing molecular pathomechanisms of ependymoma has been
      done; however, the elucidation of the processes underlying the origins of various
      clearly distinguishable ependymoma subgroups has proved to be difficult. The
      future challenges will be to reach consensus about molecular subgroups, to
      translate these into a clinical setting, and to use available models for drug
      screening and preclinical testing. RECENT FINDINGS: Ependymoma subgroups with
      clearly distinct biology have been delineated and novel mouse models generated,
      and the first high-throughput drug screens were successfully conducted leading to
      the identification of subgroup-specific active regimens. SUMMARY: Coordinated
      efforts to advance novel therapies into the clinic have led to breakthrough
      insights into the molecular biology of ependymoma. The next step will be the
      translation of preclinical findings into the clinical setting, and international
      study groups are starting to implement the most recent advances into clinical
      trials.

PMID- 23007012
TI  - Impact of ABCC2, ABCG2 and SLCO1B1 polymorphisms on the pharmacokinetics of
      pitavastatin in humans.
AB  - Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is
      distributed to the liver, a target organ of action and excreted mainly into the
      bile. To investigate the impact of influx (OATP1B1) and efflux (MRP2, BCRP)
      transporter alleles on its disposition, the pharmacokinetic (PK) parameters were
      compared among the following groups: SLCO1B1 (*15 carrier and non-carrier), ABCC2
      (G1249A, C3972T, C-24T, G1549A, and G1774T), and ABCG2 (C421A) single nucleotide
      polymorphisms in 45 healthy Korean volunteers. Pitavastatin AUC(last) was higher
      in individuals carrying the SLCO1B1*15 allele than those not carrying it (144.1
      +/- 55.3 vs. 84.7 +/- 25.7 h.ng/mL [mean +/- SD], p = 0.002). The AUC(last)
      varied significantly according to the ABCC2 C-24T allele (103.4 +/- 42.2, 80.2 +/
      23.8, and 39.0 h.ng/mL in CC, CT and TT, respectively; p = 0.027). Other SNPs of
      ABCC2 and ABCG2 were not significant. The effect of these transporters and body
      weight on the AUC(last) and C(max) were tested, and only SLCO1B1 and ABCC2 C-24T
      genotypes were significant factors by analysis of covariance. These variants
      accounted for almost 50% of the variation in AUC(last) and C(max) of
      pitavastatin. Therefore, ABCC2 C-24T was significantly associated with
      pitavastatin human PK when the known effect of SLCO1B1*15 was also considered.

PMID- 23007013
TI  - Microalbuminuria indicates long-term vascular risk in patients after acute stroke
      undergoing in-patient rehabilitation.
AB  - BACKGROUND: Patients in neurologic in-patient rehabilitation are at risk of
      cardio- and cerebrovascular events. Microalbuminuria (MAU) is frequent and an
      important risk predictor but has not been validated in in-patient rehabilitation.
      We therefore aimed to examine MAU as an indicator of risk and predictor of
      vascular events in a prospective study. METHODS: The INSIGHT (INvestigation of
      patients with ischemic Stroke In neuroloGic reHabiliTation) registry is the first
      to provide large scale data on 1,167 patients with acute stroke (< 3 months) that
      survived the initial phase of high risk and were undergoing neurologic in-patient
      rehabilitation. MAU was determined by dipstick-testing and correlated to baseline
      clinical variables (stroke-origin, functional impairment, co-morbidity, ankle
      brachial-index, intima-media-thickeness) as well as vascular events after one
      year of follow-up. Comparisons were made with the chi2 or Mann-Whitney-U Test.
      Relative risks (RR) with 95% confidence intervals (CI) were estimated using log
      binominal models. To evaluate the association between MAU and new vascular events
      as well as mortality, we calculated hazard ratios (HR) using Cox proportional
      hazard regression. RESULTS: A substantial proportion of patients was MAU positive
      at baseline (33.1%). Upon univariate analysis these patients were about 4 years
      older (69 vs. 65 years; p < 0.0001), had a slightly higher body mass index (27.8
      vs. 27.1 kg/m2; p = 0.03) and increased waist circumference (79.5 vs. 50.4% for
      women [p < 0.0001] and 46.8 vs. 43.2% for men [p = 0.04]) and twice as often had
      diabetes mellitus (41.8 vs. 20.1%; p < 0.0001). Patients with MAU had a similar
      NIH stroke scale score (median 3 vs. 3; p = 0.379) but had lower values on the
      Barthel Index (median 75 vs. 90; p < 0.001). They had higher rates of atrial
      fibrillation (RR 1.38; 95% CI 1.09-1.75), coronary artery disease (RR 1.54; 95%
      CI 1.18-2.00), heart failure (RR 1.70; 95% CI 1.10-2.60) symptomatic peripheral
      artery disease (RR 2.30; 95% CI 1.40-3.80) and atherosclerotic stroke etiology
      (53.7 vs. 35.4%; p < 0.0001). MAU was associated with an increased intima-media
      thickness, decreased ankle-brachial-index and polyvascular disease (RR 1.56;
      95%CI 1.31-1.99). The event rate after a median follow-up of 13 months was 6.7%
      for fatal or nonfatal stroke, 4.7% for death, and 10.9% for combined vascular
      events (stroke, MI, vascular death). The presence of MAU was predictive for
      vascular events during the following year (HR for total mortality 2.2; 95% CI 1.3
      3.7; HR for cardiovascular events 2.3; 95% 1.2 - 4.4). CONCLUSIONS: INSIGHT
      demonstrated a significant association between MAU and polyvascular disease and
      further supports previous findings that MAU predicts cardio-/cerebrovascular
      events in patients recovering from ischemic stroke. This biomarker may also be
      used in patients during neurologic in-patient rehabilitation, opening a window of
      opportunity for early intervention in this patient group at increased risk for
      recurrent events.

PMID- 23007014
TI  - A reappraisal of nitrogen requirements for patients with critical illness and
      trauma.
AB  - BACKGROUND: Studies regarding protein requirements for patients with critical
      illness are inconclusive owing to small sample size and population heterogeneity.
      The primary objectives of this study were to determine the amount of protein
      required to achieve nitrogen equilibrium or a positive nitrogen balance (NB, -4
      g/d or better) and ascertain whether patients with traumatic brain injury (TBI)
      exhibit greater protein catabolism than those without TBI. METHODS: Adult
      patients admitted to the trauma center, given specialized nutrition support, and
      had an NB determination within 5 days to 14 days after injury were evaluated.
      Patients with obesity, incomplete urine collection, kidney disease,
      corticosteroid or pentobarbital therapy, or an oral diet were excluded. RESULTS:
      A total of 300 NB determinations from 249 patients were evaluated. Increasing the
      protein dosage generally resulted in improved NB; however, the data were highly
      variable. Of the patients who received a protein intake of 2 g/kg per day or
      greater, 54% achieved nitrogen equilibrium or positive NB (-4 g/d or better) in
      contrast to 38% and 29% of patients who received 1.5 g/kg per day to 1.99 g/kg
      per day and 1 g/kg per day to 1.49 g/kg per day, respectively (p < 0.001). There
      was no significant difference in NB between patients with and without TBI at
      similar protein intakes. CONCLUSION: A higher protein intake was generally
      associated with an improved NB; yet, many patients remained having a negative NB.
      A protein dosage of 2 g/kg per day or greater was more successful in achieving
      nitrogen equilibrium than were lower-dosage intakes. Patients with TBI do not
      exhibit significantly greater protein catabolism than do patients without TBI.
      LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 23007015
TI  - Establishment and characteristics of an animal model for isolated pancreatic
      trauma.
AB  - BACKGROUND: There is not any stable, repeatable, and clinically simulated animal
      model of isolated pancreatic trauma been established as yet. The aim of our study
      is to establish a small animal model that mimics the pathophysiology of isolated
      pancreatic blast trauma and to study the features of traumatic condition in the
      model. METHODS: Rats were divided into three groups: calibrate group, impact
      group, and control group. The pancreas in the impact group was injured by BIM-III
      model of the biotical impact machine with the impact pressures of 800 kPa, 600
      kPa, 400 kPa, 200 kPa, and 100 kPa. The mortality, intra-abdominal structural
      changes, amylase (AMS) and lipase (LPS) activities of serum, and pathologic
      alterations of the pancreas were examined at 24 hours after trauma. We especially
      observed these changes and the variation of proliferation index in the rats
      impacted with 400 kPa pressures after 6 hours, 24 hours, 72 hours, and 7 days.
      RESULTS: Pancreatic edema, hemorrhage, cell necrosis, and vacuolization were
      found accompanied with marked increase in serum AMS and LPS. Severity of
      pancreatic histologic injury was associated with the impact pressure level and
      varied over time in the 400-kPa group. Applying 400 kPa impact pressure could be
      able to provide ideal research samples. Pancreatic trauma also induced
      compensatory proliferation of pancreatic cells. CONCLUSION: A practical animal
      model of isolated pancreatic blunt trauma could be established under 400 kPa
      pressures. It is ideal for further pathologic and therapeutic study. The combined
      determination of serum AMS and LPS, particularly the dynamic variation of these
      enzymes, might assist the diagnosis and prognosis of pancreatic trauma. Further
      research should focus on the promotion of the cellular regenerative response.

PMID- 23007016
TI  - Structural integrity of intramedullary rib fixation using a single bioresorbable
      screw.
AB  - BACKGROUND: Operative management of flail chest injury is receiving increasing
      interest. However, we have noticed in our own practice the difficulty in
      achieving reliable results with posterior rib fracture fixation. In this article,
      we analyze and model the physiologic forces acting on posterior rib fractures and
      assess the suitability of an intramedullary screw fixation technique in this
      site. METHODS: Computerized finite element analysis (FEA) was used to model a
      typical sixth rib and analyze the physiologic forces that act on the rib in vivo.
      A fracture in the posterior aspect of the rib was incorporated into the model,
      and an intramedullary screw fixation concept was assessed, using both a
      bioabsorbable polymer screw and a stainless steel screw.The records of 120
      consecutive patients with flail chest were reviewed, and 26 patients were
      identified as having multiple posterior rib fractures with displacement. These
      patients formed a clinical correlation group by which to assess the FEA model.
      RESULTS: FEA modeling of the posterior rib fracture showed likely posterior
      displacement in response to physiologic forces. Review of the 26 patients with
      flail chest and displaced posterior fractures confirmed the direction of
      displacement. Modeling of an intramedullary screw fixation showed significant
      stresses in the bone/screw contact areas (stainless steel solution) and the
      prosthesis itself (bioabsorbable polymer solution) CONCLUSION: This FEA model
      demonstrates that physiologic forces cause posterior displacement at posterior
      rib fracture sites. Fixation solutions to counteract these forces need to
      overcome significant stresses at both the bone/prosthesis contact regions and
      within the prosthetic material itself. LEVEL OF EVIDENCE:
      Epidemiologic/therapeutic study, level V.

PMID- 23007017
TI  - Delayed trauma team activation: patient characteristics and outcomes.
AB  - BACKGROUND: The study aimed to characterize factors linked to delayed trauma team
      activation (DTTA) and to establish whether these delays are linked to worse
      outcomes. METHODS: Registry data were analyzed in regard to DTTA for years 2008
      to 2010 at a Level II trauma center. DTTA was defined as cases when a trauma team
      activation or trauma consult occurred more than 30 minutes after arrival at the
      emergency department in the presence of triaging criteria or clinical evidence of
      traumatic injury. Characteristics and outcomes were studied in relation to DTTA
      using contingency tables (chi test), Student's t tests, Wilcoxon statistics, and
      multivariate methods. RESULTS: DTTA occurred in 1.5% of the 9,525 patients and
      was significantly linked to age of 55 years or older, nonwhite ethnicity, blunt
      assault (i.e., struck with blunt object), Injury Severity Score of 16 or higher,
      Glasgow Coma Scale (GCS) score of 15, and head injury with maximum Abbreviated
      Injury Scale score of 3 or higher (MAIS3+). Firearm and motor vehicular injuries
      were significantly less common among those with DTTA. No link was found for sex,
      falls, stabbings, or blood alcohol concentration (BAC) of 80 mg/dL or more.
      Although mortality did not differ, hospital stay was longer, and discharge to
      rehabilitation was more common among those with DTTA. Multivariate models
      predicting DTTA revealed significant associations with age of more than 55 years
      (odds ratio [OR], 3.77 [2.54-5.53]), white ethnicity (OR, 0.47 [0.27-0.76]),
      blunt assault (OR, 3.42 [2.20-5.19]), and GCS score of 15 (OR, 4.48 [2.02
      12.71]). Multivariate analyses did not reveal any association of DTTA with length
      of stay and mortality. CONCLUSION: DTTA occurs infrequently and is linked to
      older age, nonwhite ethnicity, blunt assaults, and normal GCS score. The higher
      rates of MAIS3+ head injuries with a maximum Abbreviated Injury Scale score of
      more than 3 among those with DTTA should encourage better recognition of those
      with these injuries. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 23007018
TI  - Total hip replacement in patients with hip fracture: a matched cohort study.
AB  - BACKGROUND: There is increasing interest in the use of total hip replacement
      (THR) for reconstruction in patients who have displaced intracapsular hip
      fractures. Patient selection is important for good outcomes, but criteria have
      only recently been clearly defined in the form of national guidelines. This study
      aimed to investigate patient reported outcomes and satisfaction after THR
      undertaken for displaced hip fractures and to compare these with a matched cohort
      of patients undergoing contemporaneous THR for osteoarthritis to assess the
      safety and effectiveness of national clinical guidelines. METHODS: One hundred
      patients were selected for treatment of displaced hip fractures using THR between
      January 1, 2007, and December 31, 2009. These patients were selected using
      national guidelines and were matched for age and sex with 300 patients who
      underwent contemporaneous THR as an elective procedure for osteoarthritis.
      RESULTS: Patients undergoing THR for both fracture and as an elective procedure
      reported excellent outcomes and satisfaction. Patients with hip fracture had
      better postoperative Oxford hip scores (p < 0.001) and SF-12 physical component
      scores (p < 0.001). Mental component scores were poorer for patients with hip
      fracture (p < 0.001). In this series, the rates of major complications for
      patients with hip fracture were higher than for elective patients. For patients
      with hip fracture, the rate of dislocation was 2%, the rate of deep infection was
      3%, and early revision operation was required for 2% of patients. The 30-day
      mortality for patients with hip fracture was zero. Nevertheless, these
      complication rates are similar to those widely reported in the literature and
      considered within acceptable limits after elective operation. CONCLUSION: For
      selected patients, THR undertaken for displaced fractures of the hip produces
      outcomes that are at least equivalent to those achieved after elective operation.
      Selection is critical to this success, and the extended use of current guidelines
      is appropriate and safe. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 23007019
TI  - Functional outcome of displaced intra-articular calcaneal fractures: a comparison
      between open reduction/internal fixation and a minimally invasive approach
      featured an anatomical plate and compression bolts.
AB  - BACKGROUND: The purpose of this study is to assess the clinical results of a
      minimally invasive treatment featured the concept of internal compression,
      including an anatomic plate and multiple compression bolts compared with open
      reduction and internal fixation for displaced intra-articular calcaneal fractures
      (DIACFs). METHODS: We retrospectively analyzed 329 patients (383 feet) who were
      identified from trauma inpatient database in our hospital for DIACFs from January
      2004 to December 2009. Of them, 148 patients (170 feet) were treated with open
      reduction and internal fixation (OR group), which involved using a traditional L
      shaped extended lateral approach, and fractures were fixed by plate and screws
      from January 2004 to December 2006; 181 patients (213 feet) were treated with a
      minimally invasive approach featured the concept of calcaneal internal
      compression (CIC group), which was achieved by an anatomic plate and multiple
      compression bolts through a small lateral incision from January 2007 to December
      2009. Postoperative complications were recorded. During follow-up, pain and
      functional outcome were evaluated with the American Orthopaedic Foot and Ankle
      Society (AOFAS) scores and compared between the two groups. Subsequent subtalar
      arthrodesis and early implant removal were performed when indicated. Routine
      hardware removal was scheduled for all patients at 1-year follow-up. RESULTS:
      There were no significant differences in sex, age, and fracture classification
      (Sanders classification) between the two groups. Wound healing complications were
      4 of 213 (1.88%) in CIC group and 20 of 170 (11.76%) in OR group. Subtalar
      arthrodesis had to be performed in one case in OR group. Four cases in CIC group
      and four cases in OR group had the hardware removed earlier due to complications.
      The average time after surgery to start weight-bearing exercise is 5.64 weeks in
      CIC group and 9.38 weeks in OR group (p < 0.001). The mean AOFAS score is higher
      in CIC group than in OR group, although the difference is not statistically
      significant (87.53 vs. 84.95; p = 0.191). The overall results according to the
      AOFAS scoring system were good or excellent in 185 of 213 (86.85%) in CIC group
      and 144 of 170 (84.71%) in OR group. The subjective portion of the AOFAS survey
      answered by patients showed statistically significant difference in activity
      limitation and walking surface score (7.31 vs. 7.02 and 3.72 vs. 3.42; p < 0.05)
      but not in pain and walking distance between the two groups (32.72 vs. 32.29 and
      4.37 vs. 4.42; p > 0.05). CONCLUSION: The study results suggest that this
      minimally invasive approach featured the concept of the calcaneal internal
      compression can achieve functional outcome as good as, if not better than the
      open techniques. It is proved to be an effective alternative treatment for
      DIACFs. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 23007020
TI  - Minimally invasive surgery for acute noncomplicated epidural hematoma: an
      innovative endoscopic-assisted method.

PMID- 23007023
TI  - Time-dependent yield of the hydrated electron in subcritical and supercritical
      water studied by ultrafast pulse radiolysis and Monte-Carlo simulation.
AB  - Fast kinetics and time-dependent yields of the hydrated electron (e(-)(aq)) in
      pure water under conditions of high temperature and pressure up to the
      supercritical region were investigated by picosecond and nanosecond pulse
      radiolysis experiments. More significant decays at short times followed by
      plateau components at longer times were observed with increasing temperature,
      suggesting faster spur reaction processes. In supercritical water, it was also
      found that the e(-)(aq) yields strongly depend on the pressure (density).
      Comparison of these measurements with Monte-Carlo computer simulations allowed us
      to identify spur reactions of e(-)(aq) that occur predominantly at high
      temperatures and also to provide new key information on certain spur model
      parameters. In particular, the experimental time-dependent e(-)(aq) yields were
      best reproduced if the electron thermalization distance decreases with increasing
      temperature. This "shrinkage" of spur sizes at high temperatures was attributed
      to an increase in the scattering cross sections of subexcitation electrons,
      likely originating from a decrease in the degree of structural order of water
      molecules as the temperature is increased.

PMID- 23007022
TI  - Human mesenchymal precursor cells (Stro-1+) from spinal cord injury patients
      improve functional recovery and tissue sparing in an acute spinal cord injury rat
      model.
AB  - This study aimed to determine the potential of purified (Stro-1(+)) human
      mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after
      transplantation into T-cell-deficient athymic RNU nude rats following acute
      moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone
      marrow (BM) stroma of SCI patients and transplanted as a suspension graft in
      medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive
      anatomical analysis shows statistically significant improvement in functional
      recovery, tissue sparing, and cyst reduction. We provide quantitative assessment
      of supraspinal projections in combination with functional outcomes. hMPC
      transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks post
      injury. Quantitative histological staining revealed that graft-recipient animals
      possessed more intact spinal tissue and reduced cyst formation than controls.
      Fluorogold (FG) retrograde tracing revealed sparing/regeneration of supraspinal
      and local propriospinal axonal pathways, but no statistical differences were
      observed compared to controls. Immunohistochemical analysis revealed increased
      serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding
      transplanted donor hMPCs 2 weeks posttransplantation, but no evidence of hMPC
      transdifferentiation was seen. Although hMPCs initially survive at 2 weeks
      posttransplantation, their numbers were dramatically reduced and no cells were
      detected at 8 weeks posttransplantation using retroviral/lentiviral GFP labeling
      and a human nuclear antigen (HNA) antibody. Additional immunosuppression with CsA
      did not improve hMPC survival or their ability to promote tissue sparing or
      functional recovery. We propose Stro-1(+)-selected hMPCs provide (i) a
      reproducible source for stem cell transplantation for SC therapy and (ii) a
      positive host microenvironment resulting in the promotion of tissue
      sparing/repair that subsequently improves behavioral outcomes after SCI. Our
      results provide a new candidate for consideration as a stem cell therapy for the
      repair of traumatic CNS injury.

PMID- 23007024
TI  - Notching up a new therapeutic strategy for non-small cell lung carcinoma (NSCLC).
AB  - Our results open a new therapeutic opportunity to treat NSCLC using GSIs.
      Interestingly, GSIs have been used in long-term treatments in Alzheimer's
      patients without major side effects (although without improving the course of the
      disease). The accumulated knowledge on the pharmacology of GSIs should pave the
      way to test these compounds in NSCLC patients.

PMID- 23007027
TI  - Abstracts of the 8th International Conference on Frontotemporal Dementias.
      Manchester, United Kingdom. September 5-7, 2012.

PMID- 23007025
TI  - Biocompatible peritoneal dialysis solution preserves residual renal function.
AB  - BACKGROUND/AIMS: The long-term effects of biocompatible peritoneal dialysis (PD)
      solution on residual renal function (RRF), inflammation, adipokines and metabolic
      acidosis are controversial. We evaluated the effects of biocompatible PD solution
      in continuous ambulatory PD (CAPD) patients for an additional 12-month period.
      METHOD: Among 91 incident patients who started CAPD with either biocompatible PD
      solution (Balance(r), Fresenius; LS, n = 48) or conventional PD solution
      (CAPD/DPCA(r), Fresenius; CS, n = 43), 63 patients, who were followed for 12
      months, were enrolled and followed for an additional 12 months. RESULTS: After 24
      months of treatment, the glomerular filtration rate (GFR) of the LS group was
      twofold higher compared to the CS group (33.5 +/- 30.7 vs. 16.3 +/- 17.9
      l/week/1.73 m(2), respectively, p = 0.021). In a subgroup of patients with an
      initial GFR >2 ml/min/1.73 m(2), the GFR of the LS group was significantly higher
      than the rate of the CS group after 24 months (43.7 +/- 30.5 vs. 18.6 +/- 19.0
      l/week/1.73 m(2), respectively, p = 0.042). Over a 24-month period, effluent
      cancer antigen-125 levels were significantly increased in the LS group compared
      to the CS group, while effluent interleukin-6 levels did not differ between the
      two groups. The serum tCO(2) levels were consistently higher in the LS group
      compared to the CS group. CONCLUSIONS: We found that the effect of LS on
      preserving RRF may be maintained over a 24-month treatment period in CAPD
      patients, and LS use may have other benefits, such as the correction of metabolic
      acidosis.

PMID- 23007028
TI  - Digested formula but not digested fresh human milk causes death of intestinal
      cells in vitro: implications for necrotizing enterocolitis.
AB  - BACKGROUND: Premature infants fed formula are more likely to develop necrotizing
      enterocolitis (NEC) than those who are breastfed, but the mechanisms of
      intestinal necrosis in NEC and protection by breast milk are unknown. We
      hypothesized that after lipase digestion, formula, but not fresh breast milk,
      contains levels of unbound free fatty acids (FFAs) that are cytotoxic to
      intestinal cells. METHODS: We digested multiple term and preterm infant formulas
      or human milk with pancreatic lipase, proteases (trypsin and chymotrypsin),
      lipase + proteases, or luminal fluid from a rat small intestine and tested FFA
      levels and cytotoxicity in vitro on intestinal epithelial cells, endothelial
      cells, and neutrophils. RESULTS: Lipase digestion of formula, but not milk,
      caused significant death of neutrophils (ranging from 47 to 99% with formulas vs.
      6% with milk) with similar results in endothelial and epithelial cells. FFAs were
      significantly elevated in digested formula vs. milk and death from formula was
      significantly decreased with lipase inhibitor pretreatment, or treatments to bind
      FFAs. Protease digestion significantly increased FFA binding capacity of formula
      and milk but only enough to decrease cytotoxicity from milk. CONCLUSION: FFA
      induced cytotoxicity may contribute to the pathogenesis of NEC.

PMID- 23007029
TI  - Glutathione peroxidase overexpression causes aberrant ERK activation in neonatal
      mouse cortex after hypoxic preconditioning.
AB  - BACKGROUND: Preconditioning of neonatal mice with nonlethal hypoxia (HPC)
      protects the brain from hypoxic-ischemic (HI) injury. Overexpression of human
      glutathione peroxidase 1 (GPx1), which normally protects the developing murine
      brain from HI injury, reverses HPC protection, suggesting that a certain
      threshold of hydrogen peroxide concentration is required for activation of HPC
      signaling. METHODS: Activation (phosphorylation) of extracellular-regulated
      kinase (ERK) 1/2 and Akt, and induction of hypoxia-inducible factor (HIF)-1alpha
      were assessed in the cortex, one of the main structures affected by HI and
      protected by HPC, at different time points after reoxygenation in wild-type (WT)
      and GPx1-overexpressing animals. RESULTS: GPx1 overexpression prevented both the
      global and nuclear increase in activated ERK at 0.5 h after HPC and caused a
      significant decrease in phospho-ERK (pERK)/ERK levels at 24 h after HPC. In
      contrast, HIF-1alpha induction at the end of hypoxia was unaffected by GPx1
      overexpression. In the cortex of preconditioned WT animals, enhanced pERK
      staining was primarily observed in neurons and to a lower extent in astrocytes
      and endothelial cells, with a nuclear prominence. CONCLUSION: Aberrant activation
      of ERK probably explains the paradoxical reversal of HPC protection by GPx1
      overexpression. The results identify hydrogen peroxide as an important mediator
      of neuroprotective ERK signaling.

PMID- 23007030
TI  - Genetic variations in hypoxia response genes influence hypertrophic
      cardiomyopathy phenotype.
AB  - BACKGROUND: Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy
      (HCM) are poorly understood. We investigated the association of variants in
      hypoxia-response genes with phenotype severity in pediatric HCM. METHODS: A total
      of 80 unrelated patients <21 y and 14 related members from eight families with
      HCM were genotyped for six variants associated with vascular endothelial growth
      factor A (VEGFA) downregulation, or hypoxia-inducible factor A (HIF1A)
      upregulation. Associations between risk genotypes and left-ventricular (LV)
      hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue
      expression was measured in myocardial samples from 17 patients with HCM and 20
      patients without HCM. RESULTS: Age at enrollment was 9 +/- 5 y (follow-up, 3.1 +/
      3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were
      associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P <
      0.01), prolonged E-wave deceleration time (EWDT) (P < 0.0001) and isovolumic
      relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05).
      These associations were seen in sporadic and familial HCM independent of the
      disease-causing mutation. Risk genotypes were associated with higher myocardial
      HIF1A and transforming growth factor B1 (TGFB1) expression and increased
      endothelial-fibroblast transformation (P < 0.05). CONCLUSION: HIF1A-upregulation
      and/or VEGFA-downregulation genotypes were associated with more severe septal
      hypertrophy and diastolic dysfunction and may provide genetic markers to improve
      risk prediction in HCM.

PMID- 23007031
TI  - Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose
      metabolism in hepatocytes of IUGR rats with catch-up growth.
AB  - BACKGROUND: Individuals with intrauterine growth retardation (IUGR) who
      demonstrate a catch-up in body weight are prone to insulin resistance. High
      expressions of suppressor of cytokine signaling 3 (SOCS3) are thought to
      aggravate insulin resistance. We hypothesized that downregulating SOCS3
      expression via small interfering RNA (siRNA) might have beneficial effects on
      insulin-resistant hepatocytes of catch-up growth IUGR rats (CG-IUGRs). METHODS:
      An IUGR rat model was employed via maternal nutritional restriction. After
      evaluating metabolic states of CG-IUGR offspring, effective SOCS3-specific siRNA
      (siSOCS3) was transfected into cultured hepatocytes using liposomes. mRNA levels
      of SOCS3, insulin receptor substrates (IRSs), phosphatidylinositol 3-kinase
      (PI3K), and Akt2, key gluconeogenesis genes, were assessed via real-time PCR.
      Protein expression and phosphorylation changes were evaluated via western blot.
      RESULTS: CG-IUGR hepatocytes showed increases in SOCS3 and gluconeogenic gene
      expressions, and decreases in IRS1 and PI3K expressions as compared with
      controls. After transfecting CG-IUGR hepatocytes with siSOCS3, protein levels of
      IRS1, PI3K, and phosphorylated Akt2 were higher as compared with those of
      untransfected CG-IUGR cells. Transcriptional suppression effects of
      gluconeogenesis genes were more obvious in siSOCS3-treated cells after insulin
      stimulation. CONCLUSION: Additional insights were provided to understand
      mechanisms of insulin resistance in CG-IUGR rats. Downregulating SOCS3 might
      improve insulin signaling transduction and ameliorate hepatic glucose metabolism
      in insulin-resistant CG-IUGR rats in vitro.

PMID- 23007032
TI  - Being born small for gestational age reduces white matter integrity in adulthood:
      a prospective cohort study.
AB  - BACKGROUND: Being born small for gestational age (SGA) (birth weight <10th
      percentile) is connected to decreased white matter (WM) integrity in newborns and
      increased prevalence of psychiatric symptoms in adulthood. The aims of this study
      were to investigate whether being born SGA at term affects WM integrity in young
      adulthood and to explore possible relationships between fractional anisotropy
      (FA) and pre- and perinatal factors and cognitive and psychiatric outcomes in
      adulthood in SGA and controls. METHODS: Diffusion tensor imaging and tract-based
      spatial statistics were conducted to test for voxelwise differences in FA in SGAs
      (n = 46) and controls (n = 57) at 18-22 y. RESULTS: As compared with controls
      SGAs had reduced FA in ventral association tracts and internal/external capsules.
      In the SGAs, no relationship was found between FA and intrauterine head growth in
      the third trimester, although total intelligence quotient was negatively
      correlated to FA. In controls, a positive correlation was found between FA and
      brain growth in the third trimester and maternal smoking. No relationship was
      found between FA and psychiatric measures in SGAs or controls. CONCLUSION: These
      results demonstrate that being born SGA leads to reduced WM integrity in
      adulthood, and suggest that different factors modulate the development of WM in
      SGA and control groups.

PMID- 23007033
TI  - Polyunsaturated fatty acid content of mother's milk is associated with childhood
      body composition.
AB  - BACKGROUND: The consumption of polyunsaturated fatty acids has changed, and the
      prevalence of adiposity has increased over the past 30 y. A decrease of n-3
      polyunsaturated fatty acid content in breast milk has been suggested to be a
      contributing factor. The objective of this study was to investigate the
      relationship between docosahexaenoic acid (DHA) content and n-6/n-3
      polyunsaturated fatty acid ratio in breast milk, body composition, and timing of
      adiposity rebound in children. METHODS: In the Copenhagen Prospective Study on
      Asthma in Childhood birth cohort, breast milk fatty acid profile was determined
      in 281 mothers and BMI development was prospectively followed up to the age of 7
      y in 222 children. Age and BMI at adiposity rebound were registered. Furthermore,
      fat mass determination by dual energy X-ray absorptiometry was performed in 207
      children at 6-9 y of age. RESULTS: There was a significant association between
      breast milk DHA and BMI from 2 to 7 y, fat mass, and, for the girls, age at
      adiposity rebound. No associations were found between the breast milk n-6/n-3
      polyunsaturated fatty acid ratio and body composition. CONCLUSION: Early intake
      of DHA may have an effect on body composition. Dietary habits of lactating
      mothers could contribute to the increased prevalence of obesity in Western
      societies.

PMID- 23007034
TI  - Evaluation of anti-lived and anti-fixed Leishmania (Viannia) braziliensis
      promastigote IgG antibodies detected by flow cytometry for diagnosis and post
      therapeutic cure assessment in localized cutaneous leishmaniasis.
AB  - This study aims to investigate a flow cytometry performance-based methodology to
      detect anti-live (FC-ALPA-IgG) and anti-fixed (FC-AFPA-IgG) Leishmania (Viannia)
      braziliensis promastigote IgG as a means to monitor post-therapeutic cure of
      patients with localized cutaneous leishmaniasis (LCL). Serum samples from 30 LCL
      patients infected with L. (V.) braziliensis were assayed, comparing the IgG
      reactivity before and after specific treatment with pentavalent antimonial.
      Reactivities were reported as the percentage of positive fluorescent parasites
      (PPFP), using a PPFP of 60% as a cut-off value. In the serum dilution of 1:1024,
      the positive percentage of LCL serum sample for FC-ALPA-IgG and FC-AFPA-IgG was
      86% and 90%, respectively, before treatment. Analysis of ?PPFP that represents
      the difference between PPFP after and before treatment appeared as a new approach
      to monitor post-therapeutic IgG reactivity in LCL. Our data support the
      perspective of using FC-ALPA and FC-AFPA as a useful serologic tool for diagnosis
      and for post-therapeutic follow-up of LCL patients.

PMID- 23007035
TI  - Comparing electric shock and a fearful screaming face as unconditioned stimuli
      for fear learning.
AB  - The potency of an unconditioned stimulus (UCS) can impact the degree of fear
      learning. One of the most common and effective UCSs is an electric shock, which
      is inappropriate for certain populations (e.g., children). To address this need,
      a novel fear learning paradigm was recently developed that uses a fearful female
      face and scream as the UCS. The present study directly compared the efficacy of
      the screaming female UCS and a traditional shock UCS in two fear learning
      paradigms. Thirty-six young adults completed two fear learning tasks and a
      measure of trait anxiety; fear learning was indexed with fear-potentiated startle
      (FPS) and self-reported fear ratings. Results indicated comparable FPS across the
      two tasks. However, larger overall startle responses were exhibited in the shock
      task, and participants rated the shock UCS and overall task as more aversive than
      the screaming female. In addition, trait anxiety was only related to FPS in the
      fear learning task that employed a shock as the UCS. Taken together, results
      indicate that, although both UCS paradigms can be used for fear conditioning
      (i.e., to produce differences between CS+ and CS-), the shock UCS paradigm is
      more aversive and potentially more sensitive to individual differences in
      anxiety.

PMID- 23007036
TI  - Body mass index following natural menopause and hysterectomy with and without
      bilateral oophorectomy.
AB  - OBJECTIVE: The directional and temporal nature of relationships between
      overweight and obesity and hysterectomy with or without oophorectomy is not well
      understood. Overweight and obesity may be both a risk factor for the indications
      for these surgeries and a possible consequence of the procedure. We used
      prospective data to examine whether body mass index (BMI) increased more
      following hysterectomy with and without bilateral oophorectomy compared with
      natural menopause among middle-aged women. METHODS: BMI was assessed annually for
      up to 10 years in the Study of Women's Health Across the Nation (SWAN (n=1962)).
      Piecewise linear mixed growth models were used to examine changes in BMI before
      and after natural menopause, hysterectomy with ovarian conservation and
      hysterectomy with bilateral oophorectomy. Covariates included education,
      race/ethnicity, menopausal status, physical activity, self-rated health, hormone
      therapy use, antidepressant use, age and visit before the final menstrual period
      (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy). RESULTS:
      By visit 10, 1780 (90.6%) women reached natural menopause, 106 (5.5%) reported
      hysterectomy with bilateral oophorectomy and 76 (3.9%) reported hysterectomy with
      ovarian conservation. In fully adjusted models, BMI increased for all women from
      baseline to FMP or surgery (annual rate of change=0.19 kg m(-2) per year), with
      no significant differences in BMI change between groups. BMI also increased for
      all women following FMP, but increased more rapidly in women following
      hysterectomy with bilateral oophorectomy (annual rate of change=0.21 kg m(-2) per
      year) as compared with following natural menopause (annual rate of change=0.08 kg
      m(-2) per year, P=0.03). CONCLUSION: In this prospective examination,
      hysterectomy with bilateral oophorectomy was associated with greater increases in
      BMI in the years following surgery than following hysterectomy with ovarian
      conservation or natural menopause. This suggests that accelerated weight gain
      follows bilateral oophorectomy among women in midlife, which may increase risk
      for obesity-related chronic diseases.

PMID- 23007037
TI  - Two-year outcome of laparoscopic Roux-en-Y gastric bypass in adolescents with
      severe obesity: results from a Swedish Nationwide Study (AMOS).
AB  - CONTEXT: The prevalence of obesity among adolescents has increased and we lack
      effective treatments. OBJECTIVE: To determine if gastric bypass is safe and
      effective for an unselected cohort of adolescents with morbid obesity in
      specialized health care. DESIGN, SETTING AND PATIENTS: Intervention study for 81
      adolescents (13-18 years) with a body mass index (BMI) range 36-69 kg m(-2)
      undergoing laparoscopic gastric bypass surgery in a university hospital setting
      in Sweden between April 2006 and May 2009. For weight change comparisons, we
      identified an adult group undergoing gastric bypass surgery (n=81) and an
      adolescent group (n=81) receiving conventional care. MAIN OUTCOME MEASUREMENTS:
      Two-year outcome regarding BMI in all groups, and metabolic risk factors and
      quality of life in the adolescent surgery group. RESULTS: Two-year follow-up rate
      was 100% in both surgery groups and 73% in the adolescent comparison group. In
      adolescents undergoing surgery, BMI was 45.5 +/- 6.1 (mean +/- s.d.) at baseline
      and 30.2 (confidence interval 29.1-31.3) after 2 years (P<0.001) corresponding to
      a 32% weight loss and a 76% loss of excess BMI. The 2-year weight loss was 31% in
      adult surgery patients, whereas 3% weight gain was seen in conventionally treated
      adolescents. At baseline, hyperinsulinemia (>20 mU l(-1)) was present in 70% of
      the adolescent surgery patients, which was reduced to 0% at 1 year and 3% at 2
      years. Other cardiovascular risk factors were also improved. Two-thirds of
      adolescents undergoing surgery had a history of psychopathology. Nevertheless,
      the treatment was generally well tolerated and, overall, quality of life
      increased significantly. Adverse events were seen in 33% of patients.
      CONCLUSIONS: Adolescents with severe obesity demonstrated similar weight loss as
      adults following gastric bypass surgery yet demonstrating high prevalence of
      psychopathology at baseline. There were associated benefits for health and
      quality of life. Surgical and psychological challenges during follow-up require
      careful attention.

PMID- 23007038
TI  - Trans-scleral tactile tonometry: an instrumented approach.
AB  - This article describes a feasibility study of a novel trans-scleral tonometer
      based on the use of an instrumented form of digital palpation tonometry. Similar
      to manual digital palpation tonometery, trans-scleral tonometer utilizes two
      force probes offset by a fixed distance. Force indentation data from these probes
      have been shown to correlate with the intraocular pressure (IOP) of the eye.
      Enucleated porcine eyes were used to experimentally validate the approach. The
      observed hysteresis in the force data was analyzed using an analytical model that
      accounts for the outflow of the aqueous humor. The predictions of the model
      indicate that the primary reason behind the observed hysteresis is stress
      relaxation (accommodation) in the visco-elastic corneo-scleral shell.
      Experimental data from eye distention and indentation tests were then used to
      infer the conditions under which the novel tonometer would be expected to have an
      accuracy of +/-1 mmHg. Analysis of the data shows that indentation rates should
      be kept below 0.5 mm/s for a pressure range of 10-35 mmHg. Two commonly used
      pressure control protocols were tested in an effort to ensure accurate IOP values
      during the palpation tests. Due to the large increase of IOP during digital
      palpation, the trans-scleral (intra-vitreous) pressurization was found to be
      inadequate, leading to clogging of the line by the displaced vitreous. No such
      problems were identified when the eye was pressurized through the cornea and into
      the anterior chamber. Force data from multiple palpation experiments are used to
      generate calibration curves for a two-probe conceptual tonometer. The calibration
      showed that a 10 mN of force variation corresponds to 1 mmHg of IOP change. A
      possible implementation using a contoured facial mask is also presented.

PMID- 23007039
TI  - The effect of high ambient temperature on emergency room visits.
AB  - BACKGROUND: The association between temperature and mortality has been widely
      researched, although the association between temperature and morbidity has been
      less studied. We examined the association between mean daily apparent temperature
      and emergency room (ER) visits in California. METHODS: We used a time-stratified
      case-crossover design, restricting our data to the warm seasons of 2005-2008 in
      16 climate zones. The study population included cases residing within 10 km of
      meteorologic monitors. Conditional logistic regression models with apparent
      temperature were applied by climate zone; these models were then combined in meta
      analyses to estimate overall effects. Our analyses considered the effects by
      disease subgroup, race/ethnic group, age group, and potential confounding by air
      pollutants. RESULTS: More than 1.2 million ER visits were included. Positive
      associations were found for same-day apparent temperature and ischemic heart
      disease (% excess risk per 10 degrees F = 1.7 [95% confidence interval = 0.2 to
      3.3]), ischemic stroke (2.8 [0.9 to 4.7]), cardiac dysrhythmia (2.8 [0.9 to
      4.9]), hypotension (12.7 [8.3 to 17.4]), diabetes (4.3 [2.8 to 5.9]), intestinal
      infection (6.1 [3.3 to 9.0]), dehydration (25.6 [21.9 to 29.4]), acute renal
      failure (15.9 [12.7 to 19.3]), and heat illness (393.3 [331.2 to 464.5]).
      Negative associations were found for aneurysm, hemorrhagic stroke, and
      hypertension. Most of these estimates remained relatively unchanged after
      adjusting for air pollutants. Risks often varied by age or racial/ethnic group.
      CONCLUSIONS: Increased temperatures were found to have same-day effects on ER
      admission for several outcomes. Age and race/ethnicity seemed to modify some of
      these impacts.

PMID- 23007040
TI  - Body mass index and renal cell cancer: the influence of race and sex.
AB  - BACKGROUND: Obesity is a risk factor for renal cell (or renal) cancer. The
      increasing prevalence of obesity may be contributing to the rising incidence of
      this cancer over the past several decades. The effects of early-age obesity and
      change in body mass index (BMI) on renal cancer have been studied less
      thoroughly, and the influence of race has never been formally investigated.
      METHODS: Using data gathered as part of a large case-control study of renal
      cancer (1214 cases and 1234 controls), we investigated associations with BMI at
      several time points, as well as with height. Adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs) were computed using logistic regression modeling. Race
      and sex-stratified analyses were conducted to evaluate subgroup differences.
      RESULTS: Obesity (BMI >= 30 kg/m) early in adulthood (OR = 1.6 [95% CI = 1.1 to
      2.4]) and 5 years before diagnosis (1.6 [1.1 to 2.2]) was associated with renal
      cancer. The association with early-adult obesity was stronger among whites than
      blacks (test for interaction, P = 0.006), whereas the association with obesity
      near diagnosis was marginally stronger in women than men (test for interaction, P
      = 0.08). The strongest association with renal cancer was observed for obese
      whites both in early adulthood and before interview (2.6 [1.5 to 4.4]); this
      association was not present among blacks. Estimates of the annual excess rate of
      renal cancer (per 100,000 persons) attributed to both overweight and obesity (BMI
      > 25 kg/m) ranged from 9.9 among black men to 5.6 among white women. CONCLUSION:
      Obesity, both early and later in life, is associated with an increased risk of
      renal cancer. The association with early obesity seems to be stronger among
      whites than blacks.

PMID- 23007041
TI  - Sexual networks, surveillance, and geographical space during syphilis outbreaks
      in rural North Carolina.
AB  - BACKGROUND: Sexually transmitted infections (STIs) spread along sexual networks
      whose structural characteristics promote transmission that routine surveillance
      may not capture. Cases who have partners from multiple localities may operate as
      spatial network bridges, thereby facilitating geographical dissemination. We
      investigated how surveillance, sexual networks, and spatial bridges relate to
      each other for syphilis outbreaks in rural counties of North Carolina. METHODS:
      We selected from the state health department's surveillance database cases
      diagnosed with primary, secondary, or early latent syphilis during October 1998
      to December 2002 and who resided in central and southeastern North Carolina,
      along with their sex partners and their social contacts irrespective of infection
      status. We applied matching algorithms to eliminate duplicate names and create a
      unique roster of partnerships from which networks were compiled and graphed.
      Network members were differentiated by disease status and county of residence.
      RESULTS: In the county most affected by the outbreak, densely connected networks
      indicative of STI outbreaks were consistent with increased incidence and a large
      case load. In other counties, the case loads were low with fluctuating incidence,
      but network structures suggested the presence of outbreaks. In a county with
      stable, low incidence and a high number of cases, the networks were sparse and
      dendritic, indicative of endemic spread. Outbreak counties exhibited densely
      connected networks within well-defined geographic boundaries and low connectivity
      between counties; spatial bridges did not seem to facilitate transmission.
      CONCLUSIONS: Simple visualization of sexual networks can provide key information
      to identify communities most in need of resources for outbreak investigation and
      disease control.

PMID- 23007042
TI  - Distribution-free mediation analysis for nonlinear models with confounding.
AB  - Recently, researchers have used a potential-outcome framework to estimate
      causally interpretable direct and indirect effects of an intervention or exposure
      on an outcome. One approach to causal-mediation analysis uses the so-called
      mediation formula to estimate the natural direct and indirect effects. This
      approach generalizes the classical mediation estimators and allows for arbitrary
      distributions for the outcome variable and mediator. A limitation of the standard
      (parametric) mediation formula approach is that it requires a specified mediator
      regression model and distribution; such a model may be difficult to construct and
      may not be of primary interest. To address this limitation, we propose a new
      method for causal-mediation analysis that uses the empirical distribution
      function, thereby avoiding parametric distribution assumptions for the mediator.
      To adjust for confounders of the exposure-mediator and exposure-outcome
      relationships, inverse-probability weighting is incorporated based on a
      supplementary model of the probability of exposure. This method, which yields the
      estimates of the natural direct and indirect effects for a specified reference
      group, is applied to data from a cohort study of dental caries in very-low-birth
      weight adolescents to investigate the oral-hygiene index as a possible mediator.
      Simulation studies show low bias in the estimation of direct and indirect effects
      in a variety of distribution scenarios, whereas the standard mediation formula
      approach can be considerably biased when the distribution of the mediator is
      incorrectly specified.

PMID- 23007046
TI  - Alcohol and the elderly. The European project VINTAGE: good health into older
      age. Preface.

PMID- 23007051
TI  - The Italian Helpdesk under the Regulation (EC) No. 1272/2008 (CLP): three-year
      activity and experience (2009-2011).
AB  - INTRODUCTION: The Regulation (EC) No. 1272/2008 on classification, labelling and
      packaging of substances and mixtures (CLP) sets further obligations for
      manufacturers, importers, distributors, downstream users of substances either on
      their own or in mixtures. According to the European mandate, each Member State
      has constituted its National Helpdesk to provide advice to the interested parties
      on their duties under this Regulation. In Italy, the contact point for questions
      has been established at the National Centre for Chemical Substances of the
      Istituto Superiore di Sanita. FUNCTIONS: The responders of the Italian CLP
      Helpdesk process the requests that have been submitted by the dedicated website.
      Applicants are asked to complete the form with all the required information. The
      Helpdesk staff also take part in the European network of CLP, REACH and ECHA
      Helpdesks together with the European Commission and other parties, that is the
      HelpNet. RESULTS: The present paper describes the results of the three-year
      activity of the Italian CLP Helpdesk (2009-2011).

PMID- 23007045
TI  - In defence of bioethicists of the third kind. Editorial.

PMID- 23007050
TI  - International scientific consensus on medical plantar pressure measurement
      devices: technical requirements and performance.
AB  - BACKGROUND: Since 2006, the Italian National Institute of Health (ISS) has been
      conducting independent scientific activities to standardize the technical
      assessment of plantar pressure measurement devices (PMDs). MATERIAL AND METHODS:
      On the basis of the ISS results, in 2010 the Pedobarographic Group of the
      International Foot and Ankle Biomechanics community (i-FAB-PG) promoted a
      Consensus activity about the main technical requirements for the appropriate use
      of PMDs. The activity relied on a moodlebased on-line forum, documents exchange,
      discussions, reviews, meetings and a final survey. RESULTS: The participation of
      clinical and technical researchers, users, and manufacturers, contributed to the
      delivery of the hereby reported recommendations which specifically regard Medical
      PMDs in the form of platforms. CONCLUSIONS: The i-FAB-PG community reached
      overall agreement on the recommendations, with a few minor objections which are
      reported and commented in the document. Relevance. The present document, the
      highest result achievable within a small scientific community, will hopefully
      represent the starting point of the wider process of establishing official
      international guidelines or standards, within scientific communities and
      standardization organizations.

PMID- 23007052
TI  - Myths of motherhood. The role of culture in the development of postpartum
      depression.
AB  - OBJECTIVES: This paper intends to offer a theoretical insight into the myths of
      motherhood and how these myths can bear on the pathogenesis of postpartum
      depression. METHODS: From a man's view motherhood is conceptualized as a
      necessary stage in the progress towards the attainment of femininity. This view
      is impersonal and external to the experience of motherhood. From a female
      perspective, motherhood presents itself as a conflicting situation. We will then
      focus on the necessity to construct a discourse on motherhood by using a code
      which belongs to women rather than men. The analysis of a blog and a comedy show
      will provide evidence concerning the evolution of the female discourse on
      motherhood thus contributing to the debunking of the myths of motherhood. The
      final section discusses ways in which myths of motherhood can bear on the
      pathogenesis of postpartum. CONCLUSIONS: Among "melancholic type" women, who tend
      to abide by social norms, play established social roles and hide their inner
      conflicts, myths of motherhood contribute to suppress the contradiction which is
      intrinsic to motherhood itself making this contradiction uncontrollable and
      potentially devastating.

PMID- 23007044
TI  - Regression models for the effects of exposure rate and cumulative exposure.
AB  - Epidemiologic studies that collect detailed exposure histories often incorporate
      this information into a regression model through a time-dependent cumulative
      exposure metric. This summary metric obscures variations in exposure rates among
      people and within persons over time. To disentangle the effects of cumulative
      exposure and exposure rate, one standard approach is to simultaneously model both
      cumulative exposure and average exposure rate. We propose an alternative
      regression model that uses a person's detailed exposure history information to
      describe the effect of the history of exposure increments on the relative hazard
      function. We illustrate this approach using data from a cohort study of radon
      exposure and lung cancer mortality among uranium miners. Compared with a standard
      cumulative exposure-average exposure rate model, our proposed approach yielded
      somewhat stronger evidence that the radon-lung cancer mortality association is
      modified by exposure rate. At low exposure rates, the estimated excess relative
      hazard per 100 working-level months was 0.63 (95% confidence interval = 0.32
      1.37) under the standard approach, whereas under the proposed approach it was
      1.23 (0.53-3.76). The proposed approach may provide better understanding of
      relationships between a protracted exposure and disease and is readily
      implemented using existing statistical software.

PMID- 23007043
TI  - Exposure during pregnancy to glycol ethers and chlorinated solvents and the risk
      of congenital malformations.
AB  - BACKGROUND: Exposure to solvents during pregnancy has long been suspected of
      increasing the risk of congenital malformations, but the lack of prospective
      assessment of specific solvent exposures has prevented definitive conclusions.
      METHODS: In a cohort of 3421 pregnant women in Brittany (2002-2006), occupational
      solvent exposure was assessed from self-report during pregnancy and from a job
      exposure matrix. Congenital malformations were diagnosed among live births,
      stillbirths, and medical pregnancy terminations. In a nested case-control sample,
      urinary concentrations of 10 metabolites of glycol ethers and chlorinated
      solvents were measured in maternal samples collected during early pregnancy (n =
      79 cases, 580 controls). RESULTS: Dose-response trends linked occupational
      solvent exposure (both self-reported and based on a job-exposure matrix) to the
      risk of major congenital malformations--especially oral clefts, urinary tract
      malformations, and male genital malformations. Detection of some glycol ether
      metabolites and trichloroacetic acid in urine was associated with increased risks
      of oral clefts and of urinary tract and limb defects. CONCLUSIONS: This
      prospective study, using three independent methods of exposure assessment,
      suggests several specific associations between solvent exposure during early
      pregnancy and congenital malformations. Results based on urinary biomarkers,
      although limited by small numbers, identify work situations that require further
      investigation.

PMID- 23007048
TI  - Alcohol and older people from a public health perspective.
AB  - OBJECTIVES AND METHODS: As part of the European project VINTAGE, a systematic
      review of scientific literature was undertaken to document the evidence base on
      the impact of alcohol on the health and well-being of older people, and on
      effective policies and preventive approaches to face the problem in this steadily
      increasing segment of the population. RESULTS: 369 references were identified,
      from which 78 papers were selected. CONCLUSIONS: The review confirms the paucity
      of data on this topic and the need for more specific research. Although there is
      scarce evidence, the elderly seems to respond equally well to alcohol policy,
      screening instruments and brief interventions as do younger adults. According to
      a lifecycle approach, a future focus on the middle aged is also recommended.

PMID- 23007054
TI  - Longevity and health expectancy in an ageing society: implications for public
      health in Italy.
AB  - INTRODUCTION: While the prolongation of life expectancy is due to medical,
      economic, social and public health advancements, longevity may not necessarily be
      an indicator of real development. Epidemiologic data indicate, in fact, that
      advanced age carries the risk of multiple diseases, disability and loss of
      autonomy. MATERIALS AND METHODS: How the years gained are lived need to be
      assessed evaluating quality of life, health status, and disability. RESULTS AND
      CONCLUSIONS: Good health care planning should aim to ensure that the years of
      life gained are lived in good health conditions in the light of the World Health
      Organization's declaration that "increased longevity without quality of life is
      an empty prize. Health expectancy is more important than life expectancy"

PMID- 23007055
TI  - Mesothelioma mortality surveillance and asbestos exposure tracking in Italy.
AB  - INTRODUCTION: Spatial distribution of mortality from pleural mesothelioma (which
      in the ICD-10 Revision has a specific code: C45.0) in Italy for the period 2003
      2009 is described. Previous mortality studies at national level employed the
      topographic code "Malignant neoplasms of pleura", because of unavailability of a
      specific code in ICD-9 Revision for pleural mesothelioma. METHODS: Standardized
      mortality ratios were computed for all municipalities, using each regional
      population as reference; for municipalities in Regions with rate higher than the
      national rate, the latter has been used as reference. SMRs were computed
      specifically also for each Italian Polluted Sites "of national concern for
      environmental remediation" (IPS) with asbestos exposure sources, composed by one
      or more municipalities, using regional rate as reference. Spatial Scan Statistics
      procedure, using SatScan software, was applied in cluster analysis: the country
      was divided into geographic macro-areas and the relative risks (RR) express the
      ratio of risk within the cluster to the risk of the macro-area outside the
      cluster. Clusters with p-value < 0.10 were selected. RESULTS: The national
      standardized annual mortality rate was 1.7 cases per 100 000. Several areas with
      evident burden of asbestos-related disease were detected. Significant clusters
      were found in correspondence to asbestos-cement industries (e.g. Casale
      Monferrato, women: RR = 28.7), shipyards (e.g. Trieste, men: RR = 4.8),
      petrochemical industries (e.g. Priolo, men: RR = 6.9) and a stone quarry
      contaminated by fluoro-edenite fibres (Biancavilla, women: RR = 25.9). Some of
      the increased clusters correspond to IPS. CONCLUSIONS: The results may contribute
      to detect asbestos exposure and to set priorites for environmental remediation.

PMID- 23007053
TI  - Clinical features and lifestyle of patients with amyotrophic lateral sclerosis in
      Campania: brief overview of an Italian database.
AB  - BACKGROUND: Physical activity and occupational exposures appeared to play a
      relevant role in pathogenesis of amyotrophic lateral sclerosis (ALS), a
      neurodegenerative disease of unknown origin. MATERIALS AND METHODS: We aimed to
      make an overview of the clinical characteristics and lifestyle (occupation and
      sport) of a population of 395 patients with ALS from Campania, in southern Italy.
      RESULTS: ALS onset resulted anticipated of about 11 years in industry workers,
      whilst the more frequent site of onset among farmers was upper limbs. Compared to
      non-athletes, athletes, particularly soccer players, showed a 7 years
      anticipation of ALS onset, with higher mortality after 5 years. DISCUSSION AND
      CONCLUSIONS: We suggest that subjects genetically prone to abnormal response to
      hypoxia during strenuous physical activity or exposed to neurotoxic agents, such
      as athletes, farmers or industry workers, might present increased risk to develop
      ALS. Future case-control and follow-up studies on our population should be
      implemented to deepen the present results.

PMID- 23007056
TI  - Integrating gender medicine into the workplace health and safety policy in the
      scientific research institutions: a mandatory task.
AB  - BACKGROUND: Gender medicine is a multi-faceted field of investigation integrating
      various aspects of psycho-social and biological sciences but it mainly deals with
      the impact of the gender on human physiology, pathophysiology, and clinical
      features of diseases. In Italy, the Decree Law 81/2008 recently introduced the
      gender issue in the risk assessment at the workplaces. AIMS: This review briefly
      describes our current knowledge on gender medicine and on the Italian legislation
      in risk management. CONCLUSIONS: Public or private scientific institutions should
      be the first to pay attention to the safety of their workers, who are
      simultaneously subjected to biological, chemical and physical agents. Main tasks
      of risk management in scientific research institutions are here analyzed and
      discussed in a gender perspective.

PMID- 23007049
TI  - Good practices for the prevention of alcohol harmful use amongst the elderly in
      Europe, the VINTAGE project.
AB  - INTRODUCTION: There is a lack of information about initiatives aimed at
      preventing the harmful effects of alcohol amongst the elderly. OBJECTIVES: One of
      the objectives of the VINTAGE study was to collect the initiatives carried out in
      Europe and review the published grey literature about this topic. METHODS: Email
      based survey addressed to researchers, professionals and policymakers, and
      internet search of grey literature. RESULTS: Three hundred nine contacts were
      finally made, and 21 of the 36 collected initiatives were considered as useful in
      preventing the harmful use of alcohol amongst the elderly. Out of the about 2900
      references identified 96 were classified as relevant. CONCLUSIONS: Despite a
      growing interest, alcohol use in the elderly is not yet perceived as a major
      issue for prevention.

PMID- 23007058
TI  - End-of-life decision making in respiratory failure. The therapeutic choices in
      chronic respiratory failure in a 7-item questionnaire.
AB  - INTRODUCTION: The transition from paternalistic medicine to a healthcare culture
      centred on the patient's decision making autonomy presents problems of
      communication and understanding. Chronic respiratory failure challenges patients,
      their families and caregivers with important choices, such as invasive and non
      invasive mechanical ventilation and tracheostomy, which, especially in the case
      of neuromuscular diseases, can significantly postpone the end of life. MATERIAL
      AND METHODS: A 7-item questionnaire was administered to 100 patients with
      advanced COPD, neuromuscular diseases and pulmonary fibrosis, all of them on
      oxygen therapy and receiving day-hospital treatment for respiratory failure. The
      objective was to find out whether or not patients, if faced with a deterioration
      of their health condition, would want to take part in the decision making process
      and, if so, how and with whom. RESULTS: Results showed that: 90% of patients
      wanted to be interviewed, 10% preferred not to be interviewed, 82% wanted to be
      regularly updated on their clinical situation, 75% wanted to be intubated, if
      necessary, and 56% would also agree to have a tracheostomy. These choices have
      been confirmed one year later, with 93% of respondents accepting the
      questionnaire and considering it useful. CONCLUSIONS: It is possible to conclude
      that a simple questionnaire can be a useful tool contributing to therapeutic
      decision making in respiratory failure.

PMID- 23007060
TI  - The involvement of mitogen-activated protein kinases in the 1alpha,25-dihydroxy
      cholecalciferol-induced inhibition of adipocyte differentiation in vitro.
AB  - The present study was undertaken to investigate the mechanism by which 1alpha, 25
      dihydroxy-cholecalciferol [1alpha,25-(OH)2-VD3] modulates the differentiation of
      mouse 3T3-L1 preadipocytes into mature adipocytes. Treatment with 1alpha,25-(OH)2
      VD3 in the presence of insulin, dexamethasone and 3-isobutyl-1-methyl-xanthine
      significantly inhibited the triacylglycerol accumulation, and mRNA expressions of
      adipocytokines (adiponectin and tumor necrosis factor-alpha) and plasminogen
      activator inhibitor-1 in the pico-nanomolar concentration range, indicating that
      1alpha,25-(OH)2-VD3 under physiological conditions inhibits the differentiation
      of 3T3-L1 cells. 1alpha,25-(OH)2-VD3 potently reduced the mRNA and/or protein
      expressions of CCAAT-enhancer binding protein alpha (C/EBPalpha) and peroxisome
      proliferator-activated receptor gamma (PPARgamma), and the nuclear translocation
      of PPARgamma. Furthermore, it inhibited the mRNA expression and phosphorylation
      of extracellular signal-regulated kinase (ERK), one of mitogen-activated protein
      kinases. These results indicate that 1alpha,25-(OH)2-VD3 can be an inhibitor of
      adipocyte differentiation, and suggest, in addition to C/EBPalpha and PPARgamma,
      an important role of ERK in mediating 1alpha,25-(OH)2-VD3-induced alteration in
      adipocyte differentiation.

PMID- 23007059
TI  - Drug shortages and clinicians: no time for complacency.

PMID- 23007057
TI  - The potential role of vitamin D for prevention and treatment of tuberculosis and
      infectious diseases.
AB  - INTRODUCTION: Vitamin D deficiency (VDD) is a common condition among several
      populations in the world. VDD is associated with higher incidence of immune
      system disorders and faster progression of some infectious diseases. Vitamin D is
      known to be of physiological importance, it is considered an essential
      micronutrient for the bone health and plays a beneficial role in the prevention
      and/or treatment of a number of chronic diseases. Vitamin D has a complex action
      on the immune system. RESULTS: Evidence that vitamin D protects against
      tuberculosis has been supported by in vitro, epidemiological and some preliminary
      clinical studies. Vitamin D has a potential effect on HIV (human immunodeficiency
      virus) and plays a crucial role in the defence against respiratory infections.
      CONCLUSIONS: Vitamin D supplementation could be a low-cost, practical method to
      protect groups of people with high incidence of those diseases. Public health
      education should stress the need for adequate dietary intake of vitamin D in
      those vulnerable groups.

PMID- 23007047
TI  - Alcohol and older people. The European project VINTAGE: good health into older
      age. Design, methods and major results.
AB  - OBJECTIVES: The European project VINTAGE - Good Health Into Older Age aims at
      filling the knowledge gap and building capacity on alcohol and the elderly,
      encouraging evidence- and experience-based interventions. METHODS: Systematic
      review of scientific literature on the impact of alcohol on older people; ad hoc
      survey and review of grey literature to collect EU examples of good practices for
      prevention; dissemination of findings to stakeholders involved in the field of
      alcohol, aging or public health in general. RESULTS: Design and procedures of the
      VINTAGE project are described, providing also an outline of major results, with
      particular attention to those related to the dissemination activity. CONCLUSIONS:
      Much more information and research is needed. This issue should be part of both
      alcohol and healthy ageing policies.

PMID- 23007064
TI  - Dietary energy density is inversely associated with the diet quality indices
      among Iranian young adults.
AB  - Dietary energy density (DED) might be associated with the quality of the consumed
      diet. Therefore, this study was conducted to report the relationship between
      dietary energy density and diet quality index in Iranian youths. In this cross
      sectional study we enrolled 410 female young adults in Isfahan-Iran who were
      selected according to the stratified random sampling method from among students
      of Isfahan University of Medical Sciences. A validated semi quantitative food
      frequency questionnaire was used to assess the usual dietary intakes. Dietary
      energy density was calculated as each individual's reported daily energy intake
      (kcal/d) into total weight of foods (excluding beverages) consumed (g/d). Diet
      quality was assessed by healthy eating index (HEI), nutrient adequacy ratio
      (NAR), and mean adequacy ratio (MAR). For calculating the NAR the ratio of daily
      individual intakes to standard recommended amounts for the subject's sex and age
      category was used. MAR was calculated as the sum of NARs divided by the number of
      nutrients (n=10). Mean dietary energy density was 1.5+/-0.2 kcal/g and mean HEI
      was 57.5+/-16.0. Those in the highest quartile of DED had the lowest value for
      HEI, MAR, and NAR of zinc, calcium, vitamin C, vitamin B12 and vitamin B2
      (p<0.05). Those in the highest quartile of DED had the highest prevalence of
      calcium, zinc, vitamin B2, vitamin B12, and vitamin C deficiency (p<0.05).
      Dietary energy density was inversely associated with the diet quality indices
      among Iranian young women adults.

PMID- 23007062
TI  - Effect of dietary porphyran from the red alga, Porphyra yezoensis, on glucose
      metabolism in diabetic KK-Ay mice.
AB  - Porphyran (POR) from the red alga Porphyra yezoensis is a water soluble dietary
      fiber. In this study, we investigated the effect of dietary POR on glucose
      metabolism in KK-Ay mice (a model for type 2 diabetes). Mice were divided into 4
      groups and fed a diet containing 5% cellulose (control), POR, POR Arg or POR K.
      After 3 wk of feeding, plasma insulin levels and the calculated homeostasis model
      assessment-insulin resistance (HOMA-IR) index were significantly lower in the POR
      group than in the control group. Compared with the control group, plasma
      adiponectin levels were significantly increased in the POR, POR Arg and POR K
      groups. These results suggest that dietary POR should improve glucose metabolism
      in diabetes via up-regulation of adiponectin levels. In addition, the amount of
      propionic acid in the cecum of the POR group was significantly higher than in the
      control group and the profile of bacterial flora was changed by dietary POR. In
      the cecum of the POR, POR Arg and POR K groups, Bacteroides was significantly
      increased and Clostridium coccoides was significantly decreased compared with in
      the control group. The effects of dietary POR on the hindgut environment might
      contribute to the improvement of glucose metabolism.

PMID- 23007061
TI  - Ingestion of cinnamaldehyde, a TRPA1 agonist, reduces visceral fats in mice fed a
      high-fat and high-sucrose diet.
AB  - Cinnamaldehyde (CNA), a pungent compound in cinnamon or dried bark of cassia, is
      a TRPA1 agonist. The effect of 0.1-1.0% CNA on pair-fed mice with high fat and
      high sucrose (HFS) diet for 1 mo was investigated. The total food intake was
      similar in the mice fed control and CNA diets, but the body weight showed a
      tendency to be lower in CNA-fed mice than in control mice. By adding CNA at 0.1,
      0.5, and 1.0% concentrations, the weight of the mesenteric adipose tissue
      decreased significantly, and there was a tendency foward lower perirenal and
      epididymal adipose tissue weights compared to the control. No differences were
      found in any blood component measured. UCP1 protein levels in the interscapular
      brown adipose tissue were higher in the 0.5 and 1.0% CNA groups than in the HSF
      group, as shown by Western blotting. Collectively, these data show that the
      addition of CNA diminishes visceral fat deposition in HFS diet-fed mice, in part
      by stimulating interscapular brown adipose tissue.

PMID- 23007069
TI  - Blood folate concentrations analyzed by microbiological assay and
      chemiluminescent immunoassay methods.
AB  - A limited number of studies have been available to compare blood folate
      concentrations by the microbiological assay (MA) method with those using the
      chemiluminescent immunoassay (CLIA) method. We compared folate concentrations
      measured by Lactobacillus rhamnosus MA with those measured by CLIA (Access
      Immunoassay Systems) in human plasma/serum and erythrocytes pairs (n=35). The
      mean plasma folate by MA was significantly higher than that by CLIA (p<0.0001),
      whereas the mean erythrocyte folate by MA was significantly lower than that by
      the CLIA method (p<0.001). Plasma folate by MA significantly correlated with
      serum folate by CLIA (r=0.85, p<0.001). Similarly, the correlation between
      erythrocyte folate measured by MA and CLIA methods was significant (r=0.87,
      p<0.001). We conclude that folate concentrations obtained by CLIA are different
      from those obtained by MA, suggesting that it is undesirable for inter-laboratory
      comparisons when folate values are obtained by different methods. Although we
      evaluated only one CLIA method, we recommend careful evaluation of folate assay
      by each CLIA method before the use in clinical and research settings.

PMID- 23007067
TI  - Characterization of corrinoid compounds from edible cyanobacterium Nostochopsis
      sp.
AB  - Vitamin B12 content of an edible cyanobacterium, Nostochopsis sp. was determined
      to be 140.6+/-16.2 MUg/100 g dry weight by a microbiological method. To evaluate
      whether the Nostochopsis cells contain vitamin B12 or inactive corrinoid
      compounds, corrinoid compounds were purified from the cells and then identified
      as pseudovitamin B12 (97.4+/-11.8 MUg/100 g dry weight) and vitamin B12 (43.2+/
      6.0 MUg/100 g dry weight) on the basis of silica gel 60 TLC bioautograms and
      LC/ESI-MS/MS chromatograms. Vitamin B12 content was significantly increased in
      the Nostochopsis cells (254.8+/-17.6 MUg/100 g dry weight) grown in the vitamin
      B12-supplemented medium.

PMID- 23007063
TI  - Effect of dietary supplementation with folate on choline deficiency-induced
      hyperhomocysteinemia in rats.
AB  - The effects of dietary supplementation with folate (20 mg/kg diet), 2.5% serine,
      or both on choline deprivation-induced hyperhomocysteinemia were investigated in
      rats fed a 10% casein diet (10C) or 25% soybean protein diet (25S) to determine
      whether folate supplementation with or without serine can suppress choline
      deficiency-induced hyperhomocysteinemia. Choline deprivation-induced enhancement
      of plasma homocysteine concentration was significantly suppressed by
      supplementation with folate, serine, or both, but the effects of these
      supplements were partial or limited in the rats fed both 10C and 25S. The extents
      of suppression of plasma homocysteine increments by folate, serine, or both were
      29.6, 37.8, and 46.2%, respectively, in rats fed 10C and 27.2, 36.6, and 42.8%,
      respectively, in rats fed 25S. There was no significant additive effect between
      folate and serine, a source of C1 units. Folate supplementation with or without
      serine significantly increased or tended to increase hepatic 5
      methyltetrahydrofolate concentration together with methionine synthase (MS) and
      cystathionine beta-synthase (CBS) activities and MS mRNA level in both rats fed
      10C and rats fed 25S. Hepatic betaine-homocysteine S-methyltransferase activity
      was unaffected by folate with or without serine. Supplementation with serine
      alone significantly increased hepatic serine concentration and increased or
      tended to increase CBS activity slightly. It is thought that the suppressive
      effect of folate on choline deficiency-induced hyperhomocysteinemia was due to
      increased metabolism of homocysteine via the MS pathway and that the suppressive
      effect of serine was due to increased metabolism of homocysteine via
      cystathionine formation. One of the reasons for the insufficient effect of folate
      alone or in combination with serine is thought to be that the capacity of the MS
      pathway for homocysteine metabolism is less enhanced by supplementation with
      folate and serine.

PMID- 23007072
TI  - Endothelial chemokine receptors as facilitators of tumor cell extravasation?
AB  - Metastasis is a multistep process characterized by the ability of tumor cells to
      "communicate" and to interact with their microenvironment to establish tumors in
      distant organs. A significant proportion of the metastatic microenvironment
      consists of leukocytes, mostly of the innate immune system, contributing to tumor
      invasion and outgrowth.

PMID- 23007066
TI  - Gallated form of tea catechin, not nongallated form, increases fecal starch
      excretion in rats.
AB  - This study was carried out to elucidate the structural advantage of a gallated
      form of tea catechin on modulating bioavailability of dietary starch in rats.
      Animal studies demonstrated that the addition of 0.5% (w/w) (-)-epigallocatechin
      gallate (EGCG) to the diet brought about a significant increase in the starch
      content in the feces collected for 2 d at the fourth week of feeding over that
      with the control diet. Of the gross starch that the rats consumed from their
      respective diets during the fecal collection period, 0.1% (for control diet) and
      1.9% (for EGCG diet) were estimated to be excreted in the feces. However, such a
      significant increase in the fecal excretion of starch by the EGCG diet was lost
      by undergoing hydrolysis of EGCG to (-)-epigallocatechin (EGC) and gallic acid
      (GA). In vitro investigation also showed that EGCG inhibited porcine pancreatic
      alpha-amylase activity in a concentration-dependent fashion, whereas the
      hydrolyzed preparation (the mixture of EGC and GA) exhibited a lack of the
      inhibitory activity for alpha-amylase. The modification of dietary starch
      digestion by inhibiting intestinal alpha-amylase activity with EGCG may be
      responsible at least in part for increasing fecal output of starch in rats. Thus,
      the attachment of a galloyl moiety to the tea flavan-3-ol skeleton may be of key
      importance for reducing intestinal digestion of dietary starch in rats.

PMID- 23007068
TI  - Urinary excretion of water-soluble vitamins increases in streptozotocin-induced
      diabetic rats without decreases in liver or blood vitamin content.
AB  - It is thought that the contents of water-soluble vitamins in the body are
      generally low in diabetic patients because large amounts of vitamins are excreted
      into urine. However, this hypothesis has not been confirmed. To investigate this
      hypothesis, diabetes was induced in male Wistar rats (6 wk old) by streptozotocin
      treatment, and they were then given diets containing low, medium or sufficient
      vitamins for 70 d. The contents of 6 kinds of B-group vitamins, namely vitamin
      B1, vitamin B2, vitamin B6, vitamin B12, folate and biotin, were determined in
      the urine, blood and liver. No basic differences among the dietary vitamin
      contents were observed. The urinary excretion of vitamins was higher in diabetic
      rats than in control rats. The blood concentrations of vitamin B12 and folate
      were lowered by diabetes, while, those of vitamin B1, vitamin B2, vitamin B6, and
      biotin were not. All liver concentrations of vitamins were increased in diabetic
      rats above those in control rats. These results showed that streptozotocin
      induced diabetes increased urinary excretion of water-soluble vitamins, though
      their blood and liver concentrations were essentially maintained in the rats.

PMID- 23007065
TI  - Branched-chain amino acid supplementation during a 100-km ultra-marathon--a
      randomized controlled trial.
AB  - Ultra-marathon running is supposed to increase the parameters of skeletal muscle
      damage and impair renal function. The purpose of this study was to investigate
      the effect of branched-chain amino acid supplementation on skeletal muscle damage
      and renal function during a 100-km ultra-marathon. Twenty-eight athletes were
      randomly divided into two groups, one group using branched-chain amino acid
      supplementation (BCAA) and a control group (CON). The athletes in the BCAA group
      were supplemented with a total of 50 g of an amino acid concentrate including 20
      g of BCAA. The intake of energy, antioxidants and parameters of both skeletal
      muscle damage and renal function were determined. Race time was not different
      between BCAA and CON when controlled for the personal best time in a 100-km ultra
      marathon. Neither the intake of energy and antioxidants nor the parameters of
      skeletal muscle damage and renal function were different between BCAA and CON. We
      concluded that BCAA-supplementation before and during a 100-km ultra-marathon had
      no effect on performance, skeletal muscle damage or renal function.

PMID- 23007070
TI  - Apple leaf extract as a potential candidate for suppressing postprandial
      elevation of the blood glucose level.
AB  - While the industrial value of fruits has long been recognized, only recently have
      the leaves of fruit trees been considered to have immense and mostly-untapped
      potential. In the present study, the physiological effects of apple leaf extract
      in mice were investigated. In addition, we sought to elucidate the active
      principle(s) and examined its potential for application. Apple leaf extract
      suppressed postprandial elevation of the blood glucose level and increased the
      residual amount of glucose in the small intestine in glucose-loaded mice compared
      with those in control mice. Bioassay-guided fractionation led to an active
      component that was identified as phloridzin, a known SGLT inhibitor, based on an
      analysis of its spectral data. With regard to an anti-hyperglycemic effect,
      extraction with ethanol from leaves of apple tree gave the best results. These
      effects decreased with heating during the extraction procedure. Since bolus
      ingestion of the extract did not affect blood glucose levels in normal mice with
      or without an overnight fast, the inhibitory effects on glucose absorption were
      not considered to be associated with unspecific gastrointestinal impairment and
      the extract did not cause hypoglycemia at a normally effective dose. Therefore,
      the leaf parts of apple tree may be a promising candidate as an industrial
      resource for maintaining good health in the future.

PMID- 23007073
TI  - Charge-distribution-related regioisomerism of photoresponsive metal-organic
      polymeric chains.
AB  - Ligand-originated isomers have been introduced into metal-organic materials to
      yield two complexes with almost the same coordination linkage and packing
      geometries but different charge-distributions, which exhibit distinct
      photoresponsive behaviors in the solid state.

PMID- 23007076
TI  - Retrospective analyses of cancer trials or existing clinical databases: potential
      for highly clinically relevant hypothesis generation.

PMID- 23007075
TI  - Photonic crystal coupled plasmonic nanoparticle array for resonant enhancement of
      light harvesting and power conversion.
AB  - Photonic crystal coupled with plasmonic nanoparticle arrays to form a periodic
      plasmonic architecture was prepared by loading Au nanoparticles inside the
      inverse opal TiO(2) film. The visible and near infrared light absorption was
      increased by 62% and the overall light-to-electricity conversion yield was thus
      increased by 41% compared with the control test.

PMID- 23007074
TI  - Main determinants of PON1 activity in hemodialysis patients.
AB  - BACKGROUND/AIMS: Cardiovascular diseases are the major cause of morbidity and
      mortality in hemodialysis (HD) patients. These patients present reduced
      paraoxonase 1 (PON1) activity that depends on genetic and non-genetic factors;
      however, how these factors influence PON1 activity in HD patients is poorly
      clarified. Our aim was to evaluate the influence of two polymorphisms and non
      genetic factors on PON1 activity in HD patients. METHODS: We evaluated 183 HD
      patients under recombinant human erythropoietin (rhEPO) treatment and 22 healthy
      individuals. The lipid profile [total cholesterol, triglycerides, HDL-c, LDL-c,
      apolipoprotein (Apo) A-I, Apo B, lipoprotein(a) and oxidized low-density
      lipoprotein (Ox-LDL)], inflammatory markers [adiponectin, interleukin-6 (IL-6)
      and C-reactive protein (CRP)], PON1 activity and PON1 gene polymorphisms (L55M
      and Q192R) were evaluated. RESULTS: HD patients presented higher levels of IL-6,
      CRP and Ox-LDL/LDL-c, and lower PON1 activity, total cholesterol, HDL-c, LDL-c,
      Apo A and Apo B; the most frequent genotype was heterozygosity for L55M
      polymorphism and homozygosity for the Q allele, the more frequent genotype of
      Q192R polymorphism. Multiple regression analysis identified heterozygosity and
      homozygosity for L55M and Q192R polymorphisms, very low-density lipoproteins, LDL
      c, Apo A and CRP levels, time on dialysis and rhEPO dose, as the independent
      variables significantly associated with PON1 activity. The associations with CRP,
      rhEPO and time on dialysis were negative. CONCLUSION: Our results show that the
      reduced PON1 activity in HD patients who are not under statin therapy is strongly
      associated with inflammation, longer time on dialysis and high rhEPO doses,
      suggesting that the reduction in PON1 activity may worsen the prognosis of these
      patients.

PMID- 23007077
TI  - The impact of potential islet precursor cells on islet autotransplantation
      outcomes.
AB  - Islet autotransplant patients represent excellent subjects to assess the
      posttransplant impact of islet precursors, as chronic pancreatitis (CP) causes an
      elevation of ductal cells, pancreatic precursors cells, and hormone-positive
      acinar cells. The relationship between these cell types and autograft outcomes
      should be more apparent than would be the case in the context of an allograft
      program with confounding immunological variables. To improve diabetic control
      following total pancreatectomy for CP, nonpurified islets were autotransplanted
      into the liver. Pancreas specimens were recovered from 23 patients and stained
      for antigens including: insulin, glucagon, cytokeratin 19, cytokeratin 7, and PDX
      1. In line with previous reports, the prevalence of ductal cells, non-islet
      endocrine cells and non-islet PDX-1-expressing cells was significantly higher in
      CP glands compared with normal pancreata. When correlating follow-up data (i.e.,
      fasting and stimulated C-peptide/glucose levels and HbA1c%) with pancreas
      immunoreactivity, high levels of ductal cells, non-islet PDX-1-positive cells,
      and non-islet glucagon-positive cells were associated with superior outcomes,
      detectable up to 2 years posttransplant. To conclude, the acinar parenchyma and
      ductal epithelium of the CP pancreas show an upregulation of both endocrine and
      pre-endocrine cell types, which appear to have a positive effect on islet graft
      outcomes in autotransplantation setting.

PMID- 23007081
TI  - The dynamics of food chains under climate change and nutrient enrichment.
AB  - Warming has profound effects on biological rates such as metabolism, growth,
      feeding and death of organisms, eventually affecting their ability to survive.
      Using a nonlinear bioenergetic population-dynamic model that accounts for
      temperature and body-mass dependencies of biological rates, we analysed the
      individual and interactive effects of increasing temperature and nutrient
      enrichment on the dynamics of a three-species food chain. At low temperatures,
      warming counteracts the destabilizing effects of enrichment by both bottom-up
      (via the carrying capacity) and top-down (via biological rates) mechanisms.
      Together with increasing consumer body masses, warming increases the system
      tolerance to fertilization. Simultaneously, warming increases the risk of
      starvation for large species in low-fertility systems. This effect can be
      counteracted by increased fertilization. In combination, therefore, two main
      drivers of global change and biodiversity loss can have positive and negative
      effects on food chain stability. Our model incorporates the most recent empirical
      data and may thus be used as the basis for more complex forecasting models
      incorporating food-web structure.

PMID- 23007083
TI  - Trophic cascades, invasive species and body-size hierarchies interactively
      modulate climate change responses of ecotonal temperate-boreal forest.
AB  - As the climate warms, boreal tree species are expected to be gradually replaced
      by temperate species within the southern boreal forest. Warming will be
      accompanied by changes in above- and below-ground consumers: large moose (Alces
      alces) replaced by smaller deer (Odocoileus virginianus) above-ground, and small
      detritivores replaced by larger exotic earthworms below-ground. These shifts may
      induce a cascade of ecological impacts across trophic levels that could alter the
      boreal to temperate forest transition. Deer are more likely to browse saplings of
      temperate tree species, and European earthworms favour seedlings of boreal tree
      species more than temperate species, potentially hindering the ability of
      temperate tree species to expand northwards. We hypothesize that warming-induced
      changes in consumers will lead to novel plant communities by changing the filter
      on plant species success, and that above- and below-ground cascades of trophic
      interactions will allow boreal tree species to persist during early phases of
      warming, leading to an abrupt change at a later time. The synthesis of evidence
      suggests that consumers can modify the climate change-induced transition of
      ecosystems.

PMID- 23007080
TI  - Universal temperature and body-mass scaling of feeding rates.
AB  - Knowledge of feeding rates is the basis to understand interaction strength and
      subsequently the stability of ecosystems and biodiversity. Feeding rates, as all
      biological rates, depend on consumer and resource body masses and environmental
      temperature. Despite five decades of research on functional responses as
      quantitative models of feeding rates, a unifying framework of how they scale with
      body masses and temperature is still lacking. This is perplexing, considering
      that the strength of functional responses (i.e. interaction strengths) is
      crucially important for the stability of simple consumer-resource systems and the
      persistence, sustainability and biodiversity of complex communities. Here, we
      present the largest currently available database on functional response
      parameters and their scaling with body mass and temperature. Moreover, these data
      are integrated across ecosystems and metabolic types of species. Surprisingly, we
      found general temperature dependencies that differed from the Arrhenius terms
      predicted by metabolic models. Additionally, the body-mass-scaling relationships
      were more complex than expected and differed across ecosystems and metabolic
      types. At local scales (taxonomically narrow groups of consumer-resource pairs),
      we found hump-shaped deviations from the temperature and body-mass-scaling
      relationships. Despite the complexity of our results, these body-mass- and
      temperature-scaling models remain useful as a mechanistic basis for predicting
      the consequences of warming for interaction strengths, population dynamics and
      network stability across communities differing in their size structure.

PMID- 23007082
TI  - Climate change in metacommunities: dispersal gives double-sided effects on
      persistence.
AB  - Climate change is increasingly affecting the structure and dynamics of ecological
      communities both at local and at regional scales, and this can be expected to
      have important consequences for their robustness and long-term persistence. The
      aim of the present work is to analyse how the spatial structure of the landscape
      and dispersal patterns of species (dispersal rate and average dispersal distance)
      affects metacommunity response to two disturbances: (i) increased mortality
      during dispersal and (ii) local species extinction. We analyse the disturbances
      both in isolation and in combination. Using a spatially and dynamically explicit
      metacommunity model, we find that the effect of dispersal on metacommunity
      persistence is two-sided: on the one hand, high dispersal significantly reduces
      the risk of bottom-up extinction cascades following the local removal of a
      species; on the other hand, when dispersal imposes a risk to the dispersing
      individuals, high dispersal increases extinction risks, especially when dispersal
      is global. Large-bodied species with long generation times at the highest trophic
      level are particularly vulnerable to extinction when dispersal involves a risk.
      This suggests that decreasing the mortality risk of dispersing individuals by
      improving the quality of the habitat matrix may greatly increase the robustness
      of metacommunities.

PMID- 23007079
TI  - Novel communities from climate change.
AB  - Climate change is generating novel communities composed of new combinations of
      species. These result from different degrees of species adaptations to changing
      biotic and abiotic conditions, and from differential range shifts of species. To
      determine whether the responses of organisms are determined by particular species
      traits and how species interactions and community dynamics are likely to be
      disrupted is a challenge. Here, we focus on two key traits: body size and
      ecological specialization. We present theoretical expectations and empirical
      evidence on how climate change affects these traits within communities. We then
      explore how these traits predispose species to shift or expand their distribution
      ranges, and associated changes on community size structure, food web organization
      and dynamics. We identify three major broad changes: (i) Shift in the
      distribution of body sizes towards smaller sizes, (ii) dominance of generalized
      interactions and the loss of specialized interactions, and (iii) changes in the
      balance of strong and weak interaction strengths in the short term. We finally
      identify two major uncertainties: (i) whether large-bodied species tend to
      preferentially shift their ranges more than small-bodied ones, and (ii) how
      interaction strengths will change in the long term and in the case of newly
      interacting species.

PMID- 23007084
TI  - Climate-induced changes in bottom-up and top-down processes independently alter a
      marine ecosystem.
AB  - Climate change has complex structural impacts on coastal ecosystems. Global
      warming is linked to a widespread decline in body size, whereas increased flood
      frequency can amplify nutrient enrichment through enhanced run-off. Altered
      population body-size structure represents a disruption in top-down control,
      whereas eutrophication embodies a change in bottom-up forcing. These processes
      are typically studied in isolation and little is known about their potential
      interactive effects. Here, we present the results of an in situ experiment
      examining the combined effects of top-down and bottom-up forces on the structure
      of a coastal marine community. Reduced average body mass of the top predator (the
      shore crab, Carcinus maenas) and nutrient enrichment combined additively to alter
      mean community body mass. Nutrient enrichment increased species richness and
      overall density of organisms. Reduced top-predator body mass increased community
      biomass. Additionally, we found evidence for an allometrically induced trophic
      cascade. Here, the reduction in top-predator body mass enabled greater biomass of
      intermediate fish predators within the mesocosms. This, in turn, suppressed key
      micrograzers, which led to an overall increase in microalgal biomass. This
      response highlights the possibility for climate-induced trophic cascades, driven
      by altered size structure of populations, rather than species extinction.

PMID- 23007085
TI  - Idiosyncratic species effects confound size-based predictions of responses to
      climate change.
AB  - Understanding and predicting the consequences of warming for complex ecosystems
      and indeed individual species remains a major ecological challenge. Here, we
      investigated the effect of increased seawater temperatures on the metabolic and
      consumption rates of five distinct marine species. The experimental species
      reflected different trophic positions within a typical benthic East Atlantic food
      web, and included a herbivorous gastropod, a scavenging decapod, a predatory
      echinoderm, a decapod and a benthic-feeding fish. We examined the metabolism-body
      mass and consumption-body mass scaling for each species, and assessed changes in
      their consumption efficiencies. Our results indicate that body mass and
      temperature effects on metabolism were inconsistent across species and that some
      species were unable to meet metabolic demand at higher temperatures, thus
      highlighting the vulnerability of individual species to warming. While body size
      explains a large proportion of the variation in species' physiological responses
      to warming, it is clear that idiosyncratic species responses, irrespective of
      body size, complicate predictions of population and ecosystem level response to
      future scenarios of climate change.

PMID- 23007078
TI  - Climate change in size-structured ecosystems.
AB  - One important aspect of climate change is the increase in average temperature,
      which will not only have direct physiological effects on all species but also
      indirectly modifies abundances, interaction strengths, food-web topologies,
      community stability and functioning. In this theme issue, we highlight a novel
      pathway through which warming indirectly affects ecological communities: by
      changing their size structure (i.e. the body-size distributions). Warming can
      shift these distributions towards dominance of small- over large-bodied species.
      The conceptual, theoretical and empirical research described in this issue, in
      sum, suggests that effects of temperature may be dominated by changes in size
      structure, with relatively weak direct effects. For example, temperature effects
      via size structure have implications for top-down and bottom-up control in
      ecosystems and may ultimately yield novel communities. Moreover, scaling up
      effects of temperature and body size from physiology to the levels of
      populations, communities and ecosystems may provide a crucially important
      mechanistic approach for forecasting future consequences of global warming.

PMID- 23007087
TI  - Climate change impacts in multispecies systems: drought alters food web size
      structure in a field experiment.
AB  - Experimental data from intergenerational field manipulations of entire food webs
      are scarce, yet such approaches are essential for gauging impacts of
      environmental change in natural systems. We imposed 2 years of intermittent
      drought on stream channels in a replicated field trial, to measure food web
      responses to simulated climate change. Drought triggered widespread losses of
      species and links, with larger taxa and those that were rare for their size, many
      of which were predatory, being especially vulnerable. Many network properties,
      including size-scaling relationships within food chains, changed in response to
      drought. Other properties, such as connectance, were unaffected. These findings
      highlight the need for detailed experimental data from different organizational
      levels, from pairwise links to the entire food web. The loss of not only large
      species, but also those that were rare for their size, provides a newly refined
      way to gauge likely impacts that may be applied more generally to other systems
      and/or impacts.

PMID- 23007086
TI  - Potential consequences of climate change for primary production and fish
      production in large marine ecosystems.
AB  - Existing methods to predict the effects of climate change on the biomass and
      production of marine communities are predicated on modelling the interactions and
      dynamics of individual species, a very challenging approach when interactions and
      distributions are changing and little is known about the ecological mechanisms
      driving the responses of many species. An informative parallel approach is to
      develop size-based methods. These capture the properties of food webs that
      describe energy flux and production at a particular size, independent of species'
      ecology. We couple a physical-biogeochemical model with a dynamic, size-based
      food web model to predict the future effects of climate change on fish biomass
      and production in 11 large regional shelf seas, with and without fishing effects.
      Changes in potential fish production are shown to most strongly mirror changes in
      phytoplankton production. We project declines of 30-60% in potential fish
      production across some important areas of tropical shelf and upwelling seas, most
      notably in the eastern Indo-Pacific, the northern Humboldt and the North Canary
      Current. Conversely, in some areas of the high latitude shelf seas, the
      production of pelagic predators was projected to increase by 28-89%.

PMID- 23007088
TI  - Linking community size structure and ecosystem functioning using metabolic
      theory.
AB  - Understanding how biogeochemical cycles relate to the structure of ecological
      communities is a central research question in ecology. Here we approach this
      problem by focusing on body size, which is an easily measured species trait that
      has a pervasive influence on multiple aspects of community structure and
      ecosystem functioning. We test the predictions of a model derived from metabolic
      theory using data on ecosystem metabolism and community size structure. These
      data were collected as part of an aquatic mesocosm experiment that was designed
      to simulate future environmental warming. Our analyses demonstrate significant
      linkages between community size structure and ecosystem functioning, and the
      effects of warming on these links. Specifically, we show that carbon fluxes were
      significantly influenced by seasonal variation in temperature, and yielded
      activation energies remarkably similar to those predicted based on the
      temperature dependencies of individual-level photosynthesis and respiration. We
      also show that community size structure significantly influenced fluxes of
      ecosystem respiration and gross primary production, particularly at the annual
      time-scale. Assessing size structure and the factors that control it, both
      empirically and theoretically, therefore promises to aid in understanding links
      between individual organisms and biogeochemical cycles, and in predicting the
      responses of key ecosystem functions to future environmental change.

PMID- 23007089
TI  - Warming shifts top-down and bottom-up control of pond food web structure and
      function.
AB  - The effects of global and local environmental changes are transmitted through
      networks of interacting organisms to shape the structure of communities and the
      dynamics of ecosystems. We tested the impact of elevated temperature on the top
      down and bottom-up forces structuring experimental freshwater pond food webs in
      western Canada over 16 months. Experimental warming was crossed with treatments
      manipulating the presence of planktivorous fish and eutrophication through
      enhanced nutrient supply. We found that higher temperatures produced top-heavy
      food webs with lower biomass of benthic and pelagic producers, equivalent biomass
      of zooplankton, zoobenthos and pelagic bacteria, and more pelagic viruses.
      Eutrophication increased the biomass of all organisms studied, while fish had
      cascading positive effects on periphyton, phytoplankton and bacteria, and reduced
      biomass of invertebrates. Surprisingly, virus biomass was reduced in the presence
      of fish, suggesting the possibility for complex mechanisms of top-down control of
      the lytic cycle. Warming reduced the effects of eutrophication on periphyton, and
      magnified the already strong effects of fish on phytoplankton and bacteria.
      Warming, fish and nutrients all increased whole-system rates of net production
      despite their distinct impacts on the distribution of biomass between producers
      and consumers, plankton and benthos, and microbes and macrobes. Our results
      indicate that warming exerts a host of indirect effects on aquatic food webs
      mediated through shifts in the magnitudes of top-down and bottom-up forcing.

PMID- 23007090
TI  - Potential for climate effects on the size-structure of host-parasitoid indirect
      interaction networks.
AB  - Communities of insect herbivores are thought to be structured mainly by indirect
      processes mediated by shared natural enemies, such as apparent competition. In
      host-parasitoid interaction networks, overlap in natural enemy communities
      between any pair of host species depends on the realized niches of parasitoids,
      which ultimately depend on the foraging decisions of individuals. Optimal
      foraging theory predicts that egg-limited parasitoid females should reject small
      hosts in favour of future opportunities to oviposit in larger hosts, while time
      limited parasitoids are expected to optimize oviposition rate regardless of host
      size. The degree to which parasitoids are time- or egg-limited depends in part on
      weather conditions, as this determines the proportion of an individual's lifespan
      that is available to foraging. Using a 10-year time series of monthly
      quantitative host-parasitoid webs, we present evidence for host-size-based
      electivity and sex allocation in the common secondary parasitoid Asaphes
      vulgaris. We argue that this electivity leads to body-size-dependent asymmetry in
      apparent competition among hosts and we discuss how changing weather patterns, as
      a result of climate change, may impact foraging behaviour and thereby the size
      structure and dynamics of host-parasitoid indirect interaction networks.

PMID- 23007091
TI  - Climate change effects on macrofaunal litter decomposition: the interplay of
      temperature, body masses and stoichiometry.
AB  - Macrofauna invertebrates of forest floors provide important functions in the
      decomposition process of soil organic matter, which is affected by the nutrient
      stoichiometry of the leaf litter. Climate change effects on forest ecosystems
      include warming and decreasing litter quality (e.g. higher C : nutrient ratios)
      induced by higher atmospheric CO(2) concentrations. While litter-bag experiments
      unravelled separate effects, a mechanistic understanding of how interactions
      between temperature and litter stoichiometry are driving decomposition rates is
      lacking. In a laboratory experiment, we filled this void by quantifying
      decomposer consumption rates analogous to predator-prey functional responses that
      include the mechanistic parameters handling time and attack rate. Systematically,
      we varied the body masses of isopods, the environmental temperature and the
      resource between poor (hornbeam) and good quality (ash). We found that attack
      rates increased and handling times decreased (i) with body masses and (ii)
      temperature. Interestingly, these relationships interacted with litter quality:
      small isopods possibly avoided the poorer resource, whereas large isopods
      exhibited increased, compensatory feeding of the poorer resource, which may be
      explained by their higher metabolic demands. The combination of metabolic theory
      and ecological stoichiometry provided critically important mechanistic insights
      into how warming and varying litter quality may modify macrofaunal decomposition
      rates.

PMID- 23007092
TI  - Warming and nitrogen affect size structuring and density dependence in a host
      parasitoid food web.
AB  - Body size is a major factor constraining the trophic structure and functioning of
      ecological communities. Food webs are known to respond to changes in basal
      resource abundance, and climate change can initiate compounding bottom-up effects
      on food-web structure through altered resource availability and quality. However,
      the effects of climate and co-occurring global changes, such as nitrogen
      deposition, on the density and size relationships between resources and consumers
      are unknown, particularly in host-parasitoid food webs, where size structuring is
      less apparent. We use a Bayesian modelling approach to explore the role of
      consumer and resource density and body size on host-parasitoid food webs
      assembled from a field experiment with factorial warming and nitrogen treatments.
      We show that the treatments increased resource (host) availability and quality
      (size), leading to measureable changes in parasitoid feeding behaviour.
      Parasitoids interacted less evenly within their host range and increasingly
      focused on abundant and high-quality (i.e. larger) hosts. In summary, we present
      evidence that climate-mediated bottom-up effects can significantly alter food-web
      structure through both density- and trait-mediated effects.

PMID- 23007093
TI  - The role of temperature and dispersal in moss-microarthropod community assembly
      after a catastrophic event.
AB  - There is a clear crisis in the maintenance of biodiversity. It has been generated
      by a multitude of factors, notably habitat loss, now compounded by the effects of
      climate change. Predicted changes in climate include increased severity and
      frequency of extreme climatic events. To manage landscapes, an understanding of
      the processes that allow recovery from these extreme events is required.
      Understanding these landscape-scale processes of community assembly and
      disassembly is hindered by the large scales at which they operate. Model systems
      provide a means of studying landscape scale processes at tractable scales. Here,
      we assess the combined effects of temperature and habitat-patch isolation on
      assembly of naturally diverse moss microarthropod communities after a high
      temperature event. We show that community assembly depends on temperature and on
      degree of habitat isolation. Heated communities were heavily dominated in
      abundance by two species, one of them relatively large. The resulting size
      structure is unlike that seen in the field. Community composition in habitat
      fragments appears also to have been influenced by the source pool of recolonizing
      fauna. Our results highlight the value of dispersal in disturbed landscapes and
      the potential for habitat connectivity to buffer communities from the effects of
      climate change.

PMID- 23007094
TI  - Climate change impacts on body size and food web structure on mountain
      ecosystems.
AB  - The current distribution of climatic conditions will be rearranged on the globe.
      To survive, species will have to keep pace with climates as they move. Mountains
      are among the most affected regions owing to both climate and land-use change.
      Here, we explore the effects of climate change in the vertebrate food web of the
      Pyrenees. We investigate elevation range expansions between two time-periods
      illustrative of warming conditions, to assess: (i) the taxonomic composition of
      range expanders; (ii) changes in food web properties such as the distribution of
      links per species and community size-structure; and (iii) what are the specific
      traits of range expanders that set them apart from the other species in the
      community-in particular, body mass, diet generalism, vulnerability and trophic
      position within the food web. We found an upward expansion of species at all
      elevations, which was not even for all taxonomic groups and trophic positions. At
      low and intermediate elevations, predator : prey mass ratios were significantly
      reduced. Expanders were larger, had fewer predators and were, in general, more
      specialists. Our study shows that elevation range expansions as climate warms
      have important and predictable impacts on the structure and size distribution of
      food webs across space.

PMID- 23007095
TI  - Evaluation of Japanese encephalitis virus polytope DNA vaccine candidate in
      BALB/c mice.
AB  - Vaccination is the most important measure available to control the spread of
      Japanese encephalitis virus. We have previously described the in silico design,
      in vitro and primary in vivo analyses of polytope construct (P-JEV). Present
      study indicates that, P-JEV induces significant specific humoral and cellular
      immune responses in BALB/c mice. Mice were immunized intra-dermally with 1MUg
      plasmid DNA using gene gun and boosted twice. After the second booster, all the
      mice seroconverted and developed JEV neutralizing antibodies. Enhancement of post
      challenge neutralizing antibody titres indicates the dominant role of anamnestic
      antibody-mediated protection in the mice JEV challenge model. Our study provides
      an insight demonstrating, intra-dermal DNA administration led to higher
      seroconversion rates and potentiated T(H)2 type of immune responses. The P-JEV
      construct is thus capable of generating protective neutralizing antibodies in
      mice and prime the immune system effectively against subsequent exposure to the
      virus.

PMID- 23007096
TI  - Continuity and change in infants' sleep from 8 to 14 months: a longitudinal
      actigraphy study.
AB  - In this report changes and stability in sleep-wake characteristics, at the latter
      part of infancy, were examined. The sample comprised of 34 healthy infants whose
      sleep was assessed by means of actigraphy at 8, 10, 12 and 14 months. The results
      indicated that while sleep schedules did not change significantly from 8 to 14
      months, sleep consolidation continued across time. Age 12 months stands out in
      that sleep disruption was unrelated to whether or not the child was a frequent
      nightwaker before and/or after the 1st birthday. The findings demonstrate the
      importance of investigating sleep longitudinally using multiple time scales.

PMID- 23007097
TI  - The Infant Crying Questionnaire: initial factor structure and validation.
AB  - The current project reports on an initial investigation into the factor structure
      of the Infant Crying Questionnaire (ICQ), a measure designed to assess parental
      beliefs about infant crying, in a sample of 259 primiparous mothers. Exploratory
      factor analyses yielded evidence for a five-factor structure to the ICQ, with two
      factors that may be conceptually viewed as infant-oriented beliefs regarding
      infant crying (Attachment/Comfort and Crying as Communication) and three factors
      conceptually reflecting parent-oriented beliefs regarding infant crying
      (Minimization, Directive Control, and Spoiling). Each of the scales demonstrated
      strong internal consistency and was associated with concurrent measures of
      mothers' causal attributions about emotional responses to infant crying.
      Predictive validity to observed maternal sensitivity at 6 months and mother
      reported infant behavioral problems at one year was demonstrated. The importance
      of a questionnaire method to assess parents' beliefs regarding infant crying in
      developmental research is discussed and future methodological directions are
      outlined.

PMID- 23007098
TI  - Cationic complexes of silicon and germanium with (O,S)-chelate ligands.
AB  - Synthesis and X-ray diffraction study of cationic bischelates
      MeSi(SCH(2)CONMe(2))(2)(+)Cl(-) and MeGe(SCH(2)CONMe(2))(2)(+)Br(-) are reported.
      According to X-ray data, the Si and Ge atoms in these compounds have distorted
      TBP environments with two coordinating oxygen atoms in axial positions.

PMID- 23007099
TI  - Serum uric acid independently predicts cardiovascular events in advanced
      nephropathy.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk for
      cardiovascular (CV) disease and is also associated with elevated uric acid, which
      is emerging as a nontraditional CV risk factor. We therefore evaluated uric acid
      as a risk factor for CV disease in subjects presenting to nephrologists with CKD
      who were not on medications known to alter endothelial function. METHODS: 303
      subjects with stage 3-5 CKD were followed for a mean of 39 months (range 6-46)
      and assessed for fatal and nonfatal CV events. Hyperuricemia was defined as uric
      acid >6.0 mg/dl for women and >7.0 mg/dl for men. In addition to other CV risk
      factors, endothelial function (flow-mediated dilatation), inflammatory markers
      (hsCRP), and insulin resistance (HOMA index and fasting insulin levels) were
      included in the analysis. We evaluated the association between uric acid and flow
      mediated dilatation with linear regression. The impact of uric acid on composite
      CV events was assessed with Cox regression analysis. RESULTS: Of a total of 303
      patients, 89 had normouricemia and 214 had hyperuricemia. Both fatal (32 of 214
      vs. 1 of 89 subjects) and combined fatal and nonfatal (100 of 214 vs. 13 of 89
      subjects) CV events were more common in subjects with hyperuricemia compared with
      normal uric acid levels, and this was independent of estimated glomerular
      filtration rate, traditional CV risk factors including diabetes, hypertension and
      BMI, and nontraditional risk factors (hsCRP and endothelial function). The 46
      month survival rate was 98.7% in the group with low uric acid compared to 85.8%
      in patients with high uric acid (p = 0.002). CONCLUSIONS: Hyperuricemia is an
      independent risk factor for CV events in subjects presenting with CKD who are not
      on medications known to alter endothelial function.

PMID- 23007100
TI  - "Functional rTMS": putting the brain to work to enhance brain stimulation post
      stroke?

PMID- 23007101
TI  - Isolation and characterization of bacterial isolates algicidal against a harmful
      bloom-forming cyanobacterium Microcystis aeruginosa.
AB  - Algicidal bacteria MaI11-2, MaI11-5 and MaI11-10, which inhibited the growth of a
      harmful bloom-forming cyanobacterium Microcystis aeruginosa, were isolated from a
      sewage treatment plant. The isolate MaI11-5 was phylogenetically affiliated into
      the genus Pedobacter, while MaI11-2 and MaI11-10 were closely related to Bacillus
      aerophilus, Bacillus altitudinis and Bacillus stratosphericus with 100% identity
      based on 16S ribosomal RNA sequences. Co-cultivation of M. aeruginosa with the
      algicidal isolates showed their high algicidal activity. MaI11-5 showed the
      highest inhibitory effect on the cyanobacterial growth: the inhibitory effect
      exceeded 50% after 2 days, and reached to 75-85% after 10 days, regardless of the
      bacterial cell density. The cyanobacterial cells aggregated and produced
      mucilaginous, glycocalyx-like compounds when attacked by the algicidal bacteria.
      These results suggest that the algicidal bacteria isolated in the present study
      are potentially useful as biocontrol agents against M. aeruginosa bloom.

PMID- 23007102
TI  - Comparative study of in vitro ocular surface cytotoxicity of a fixed combination
      of 0.5% timolol/1% dorzolamide eyedrop and its components with 0.005%
      benzalkonium chloride.
AB  - We evaluated the cytotoxicity of antiglaucoma ophthalmic solutions preserved with
      the same concentration of benzalkonium chloride (BAK) in four cultured corneal
      and conjunctival cell lines. The viability of cell cultures was determined
      following the exposure of cells to timolol maleate, dorzolamide, and their fixed
      combination, Kosoputo((r)) (MSD, a Japanese formulation of Cosopt((r)) (Merck)),
      and two commercially available eyedrop solutions, 0.5% Timpotol((r)) (containing
      0.5% timolol maleate, MSD) and 1% Trusopt((r)) (containing 1% dorzolamide, MSD)
      for varying exposure times and at various dilutions using the MTT and neutral red
      assays. All the three commercially available eyedrop solutions tested in this
      study were preserved with 0.005% BAK. The toxicity of each solution was compared
      using the % cell viability score (CVS) . Cell viability was also subjected to
      statistical analysis using ANOVA, Dunnett's multiple comparison tests and a chi
      square test. %CVS50/%CVS40/80s for the tested solutions were 53/-13 for 0.5%
      Timoptol((r)), 100/88 for preservative-free 0.5% timolol maleate, 50/ -10 for 1%
      Trusopt((r)), 72/100 for preservative-free 1% dorzolamide, and 44/-17 for
      Kosoputo((r)). The results of statistical analysis were consistent to them. In
      conclusion, Kosoputo((r)) had greater cytotoxicity than each component; however,
      in actual use it may have the advantages of reduced toxicity (side effect) due to
      reduced instillation frequency, and better patient adherence to the treatment
      regimen as well as a comparable pressure reduction effect.

PMID- 23007103
TI  - Cell viability score as an integrated indicator for cytotoxicity of benzalkonium
      chloride-containing antiglaucoma eyedrops.
AB  - We evaluated the in vitro cytotoxicity of benzalkonium chloride (BAK)-containing
      antiglaucoma eyedrops. We prepared cell cultures of SIRC, BCE C/D-1b, RC-1, and
      Chang conjunctiva. The viability of cell cultures was determined using the MTT
      and neutral red assays. The cell viability score (CVS) was used to compare the
      toxicity of test solutions. %CVS50 and %CVS40/80 of each eyedrop solution were 71
      and 26 for Lumigan((r)) (0.002% bimatoprost with 0.005% BAK), 100 and 99 for
      Tapros((r)) (0.0015% tafluprost, a new formula from 2010 with 0.001% BAK), 39 and
      -29 for 2% Trusopt((r)) (2% dorzolamide with 0.0075% BAK), 28 and -43 for
      Xalacom((r)) (latanoprost/0.5% timolol with 0.02% BAK), 88 and 66 for
      DuoTrav((r)) (travoprost/0.5% timolol with no BAK), 36 and -35 for Cosopt((r))
      (2% dorzolamide/0.5% timolol with 0.0075% BAK) and 53 and -1 for Combigan((r))
      (0.15% brimonidin/0.5% timolol with 0.005% BAK). Only Xalacom((r)) and
      Tapros((r)) did not show an apparent decrease in %CVS as compared to the
      corresponding concentration of BAK. In conclusion, the cytotoxicity of tested
      eyedrops was dependent on BAK. Only the eyedrops containing latanoprost or
      tafluprost showed a reduction in the cytotoxicity of BAK.

PMID- 23007104
TI  - Microbicidal effect of weak acid hypochlorous solution on various microorganisms.
AB  - We investigated the microbicidal effect of weak acid hypochlorous solutions of pH
      5.0 - 6.0, produced by mixing NaClO and HCl in water, against various bacteria,
      fungi, and virus in vitro. The weak acid hypochlorous solution had excellent
      microbicidal effect against a broad microbicidal spectrum of standard strains and
      clinical isolates in a short time. The microbicidal effects of hypochlorous
      solutions did not depend on the available chlorine concentration but on the HClO
      concentration. These results show that the weak acid hypochlorous solution has
      practical applicability in such places as hospitals and establishments related to
      the food industry.

PMID- 23007105
TI  - Effects of parabens and isothiazolinone on the microbiological quality of baby
      shampoo: the challenge test.
AB  - An in vitro microbial challenge test has been developed to predict the likelihood
      of consumer contamination of baby shampoo. Four preservatives were tested in our
      study: the parbens Medcide D, Medcide PB, Sepicide HB. and isothiazolinone
      Methylisothiazolinone/Chloromethylisothiazolinone [MI/MCI]. These preservatives
      were tested separately and in combination. The challenge test involved
      inoculating the product with Micrococcus luteus, Staphylococcus aureus,
      Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, Aspergillus
      brasiliensis and Candida albicans. Inhibition growth of these microorganisms at
      each preservative concentration was followed over a 28 d period. The test was
      used to classify products as poorly preserved, marginally preserved, or well
      preserved. Interestingly, it was the combination (0.1% Isothiazolinone [MI/MCI]
      and 0.1% Sepicide HB) which inhibited most the microbial growth of microorganims
      while preserving the physicochemical properties of the product. As a result, the
      challenge test described can be accurately used to predict the risk of consumer
      contamination of cosmetic products.

PMID- 23007106
TI  - Bacterial degradation and reduction in the estrogen activity of 4-nonylphenol.
AB  - Bacteria capable of degrading 4-nonylphenol  (NP)  were isolated and identified,
      and their ability to degrade NP was determined. The screening of microorganisms
      in river water and soil led to a collection of 23 strains of bacteria and five
      strains of fungi. Two strains of bacteria, identified as Pseudomonas sp. and
      Acidovorax sp., possessed great ability for degrading NP. The NP degradation rate
      of Pseudomonas sp. did not change with the NP concentration  (50-100mg/L) . In
      contrast, the NP degradation rate of Acidovorax sp. increased with increasing NP
      concentration. Acidovorax sp. possessed the greatest NP degradation activity at
      35 degrees C. No NP degradation activity was observed for Pseudomonas sp. at
      temperatures higher than 30 degrees C. Even when non-NP carbon sources such as
      glucose or sucrose were added, the NP degradation rates for both bacteria did not
      decrease. In addition, the estrogenic activity of NP decreased depending on the
      amount of NP residues determined by the yeast two-hybrid system.

PMID- 23007107
TI  - Evaluation of the dry sheet medium (Compact Dry ETB(R)) for enumerating
      Enterobacteriaceae in meat samples.
AB  - Compact Dry ETB(R)  (CD-ETB, ETB; Enterobacteriaceae) , a ready-to-use and self
      diffusible dry medium sheet culture system for the detection and enumeration of
      Enterobacteriaceae, was evaluated. A total of 35 Enterobacteriaceae strains,
      which were studied for the inclusivity study, grew and formed red-purple colored
      colonies on the CD-ETB(R). When 17 gram-negative bacteria other than
      Enterobacteriaceae were inoculated for the exclusivity study, 2 strains grew and
      formed red-purple colonies, 9 strains formed colorless colonies, and 6 strains
      failed to grow. A total of 43 gram-positive bacteria and 3 yeasts failed to grow.
      The CD-ETB method was compared with the Violet Red Bile Glucose  (VRBG)  agar
      method according to ISO 21528-2 and the 3M Petrifilm(TM) EB  (3M-EB(R))  method
      in 53 meat samples. The correlation coefficients between CD-ETB(R) and VRBG agar,
      CD-ETB(R) and 3M-EB(R), and 3M-EB(R) and VRBG agar were 0.962, 0.992 and 0.960,
      respectively.

PMID- 23007109
TI  - Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to
      increase heroin dependent individuals' engagement in a full continuum of care.
AB  - Absence of successful transition to post-detoxification treatment leads to high
      rates of relapse among detoxified heroin users. The present study evaluated a
      pilot buprenorphine treatment program (BTP). Heroin dependent individuals were
      inducted onto buprenorphine/naloxone in detox, maintained while transitioning
      through an intensive inpatient program (IIP), and gradually tapered off
      medication over 5 months of outpatient (OP) treatment. Compared to programmatic
      indicators of treatment engagement in the year prior to BTP implementation,
      referrals from detox to IIP, entry into and completion of IIP and subsequent OP,
      and days in OP treatment increased substantially. BTP completers, compared to non
      completers, viewed abstinence as more difficult and as requiring more assistance
      to achieve, were less likely to be current cocaine and alcohol users or to have
      relapsed during the course of treatment. Although preliminary and in need of
      replication, initial adjunctive use of buprenorphine in an abstinence-based
      continuum of care may improve post-detoxification treatment entry, engagement,
      and completion.

PMID- 23007110
TI  - Directly administered antiretroviral therapy: pilot study of a structural
      intervention in methadone maintenance.
AB  - Devising interventions to provide integrated treatment for addiction and medical
      problems is an urgent issue. This study piloted a structural intervention,
      Directly Administered Antiretroviral Therapy (DAART), to assist methadone
      maintenance patients in HIV medication adherence. Twenty-four participants
      received: (1) antiretroviral medications at the methadone clinic daily before
      receiving their methadone; (2) take-home antiretroviral medication for days they
      were not scheduled to attend the methadone clinic, and (3) brief adherence
      counseling to address adherence barriers. DAART lasted 24 weeks, with a planned
      step-down to twice-weekly administration in weeks 25-36, followed by self
      administration in weeks 37-48. Retention rates at weeks 24, 36, and 48 were 83,
      92, and 75% respectively. DAART was associated with improvement in the proportion
      of participants achieving viral suppression as well as with high medication
      adherence rates (clinic-verified; 85% and self-reported 97%) during the active
      intervention phase. DAART was effective as an intervention but did not promote
      transition to self-administration. This study demonstrates that DAART is
      adaptable and simple enough to be implemented into methadone treatment programs
      interested in providing HIV adherence services.

PMID- 23007111
TI  - Resonant X-ray emission spectroscopy reveals d-d ligand-field states involved in
      the self-assembly of a square-planar platinum complex.
AB  - Resonant X-ray Emission Spectroscopy (RXES) is used to characterize the ligand
      field states of the prototypic self-assembled square-planar complex,
      [Pt(tpy)Cl]Cl (tpy=2,2':6',2''-terpyridine), and determine the effect of weak
      metal-metal and pi-pi interactions on their energy.

PMID- 23007112
TI  - Health policy in medical education: what young physicians know about the
      Affordable Care Act.

PMID- 23007113
TI  - Factors associated with the development of pressure ulcers after spinal cord
      injury.

PMID- 23007114
TI  - Brown-Sequard described a rare, but important syndrome.

PMID- 23007115
TI  - Letter commenting on 'Survival after short- or long-term ventilation after acute
      spinal cord injury: a single-centre 25-year retrospective study'.

PMID- 23007116
TI  - The metabolic syndrome of fructose-fed rats: effects of long-chain
      polyunsaturated omega3 and omega6 fatty acids. V. Post-mortem findings.
AB  - The present study deals with the possible effects of dietary omega3 and omega6
      fatty acids upon the metabolic syndrome found in rats exposed for 8 weeks to a
      diet containing 64% (w/w) D-fructose instead of starch. Fructose-fed rats were
      found to display a modest increase in plasma albumin and protein concentration
      and more pronounced increases in plasma urea, creatinine, phospholipids,
      triglycerides and cholesterol concentrations, glycated hemoglobin concentration
      and liver contents of cholesterol, triglycerides and phospholipids. The plasma
      concentrations of HDL-cholesterol, calcium and iron were decreased, however, in
      the fructose-fed rats. In general, the partial substitution of sunflower oil by
      either safflower oil or salmon oil opposed the metabolic perturbations otherwise
      associated with the fructose-induced metabolic syndrome in the fructose-fed rats,
      with salmon oil demonstrating particular efficacy. Consideration is given to the
      possible biological determinants of these perturbations and their attenuation in
      rats exposed to safflower or salmon oil.

PMID- 23007117
TI  - A pilot online survey assessing risk factors for HIV acquisition in the Navy and
      Marine Corps, 2005-2010.
AB  - The Department of Defense policy Don't Ask, Don't Tell (DADT) ended in September,
      2011. The Navy Bloodborne Infection Management Center conducted a post-DADT pilot
      survey of HIV seroconverters identified when the DADT policy was in effect.
      Sailors and Marines newly diagnosed as HIV positive from 2005 to 2010 were
      invited to participate in an online survey. A structured questionnaire elicited
      risk information about the 3-year period before HIV diagnosis. Respondents
      reported engaging commonly in same sex sexual activity, having concurrent
      partners, and poor condom use for anal sex. In this first post-DADT repeal report
      of self-reported behaviors, male-to-male sexual contact was a much more common
      mode of infection than previously reported. Several opportunities for primary
      prevention messaging now possible after DADT repeal are evident.

PMID- 23007119
TI  - Normal levels of vitamin D among HIV-infected Catalan pediatric patients.

PMID- 23007118
TI  - Role of GB virus C in HIV-1-infected and hepatitis C virus-infected hemophiliac
      children and adolescents.
AB  - BACKGROUND: GB Virus C (GBV-C) has been associated with a better prognosis of HIV
      1 disease in adults. Little is known about prevalence and interaction between GBV
      C, HIV-1, and/or hepatitis C virus (HCV) in hemophiliac children and adolescents.
      METHODS: A well-characterized cohort of HIV-1-infected and HIV-1-uninfected
      hemophiliac children and adolescents followed in the Hemophilia Growth and
      Development Study (HGDS) were evaluated using quantitative reverse transcription
      polymerase chain reaction to detect GBV-C RNA in samples from baseline and last
      follow-up visit. RESULTS: HIV-1-infected (n = 202) and HIV-1-uninfected (n = 119)
      patients had a low prevalence of GBV-C infection at baseline (0.9 and 0%), which
      increased at time of last follow-up visit to 25.2% and 26.3%, respectively. In
      addition, at the time of the follow-up GBV-C measurement, those GBV-C infected
      had been followed longer and had higher CD4(+) cell counts and lower HIV-1 viral
      loads than those GBV-C uninfected. These beneficial effects of GBV-C were no
      longer significant after controlling for CD4(+) cell count and HIV-1 RNA at
      baseline. HCV RNA clearance was more common amongst those who were not GBV-C
      infected than those who became GBV-C viremic. CONCLUSIONS: This study confirms a
      positive association of GBV-C with milder course of HIV-1 infection. GBV-C
      infection was associated with a higher likelihood of persistent HCV infection.

PMID- 23007120
TI  - Prevalence of prolonged amenorrhea in HIV-infected women: results from the
      Italian DIDI study.

PMID- 23007121
TI  - Vitamin D status in HIV-infected patients with and without tuberculosis: a pilot
      study.

PMID- 23007122
TI  - [Injuries of the acromioclavicular joint].

PMID- 23007123
TI  - [Treatment of acute acromioclavicular joint instability with modern
      reconstruction procedures].
AB  - During the past few years numerous arthroscopic and arthroscopically assisted
      reconstruction techniques for the stabilization of acute high-grade
      acromioclavicular joint instability have been adapted either from open procedures
      or have been made arthroscopically applicable. Currently, pulley-like implants
      are being used at an increasing rate and the short-term and mid-term clinical and
      radiological results are at least equal to open techniques.

PMID- 23007124
TI  - [Fractures of the lateral clavicle and acromion].
AB  - Fractures of the lateral clavicle and the acromion are uncommon and represent a
      separate entity. Fractures of the lateral clavicle demonstrate a high rate of
      problems, such as non-union, malunion and functional impairment when treated
      nonoperatively. The aim of any treatment option is full restoration of shoulder
      function by achieving fracture healing without significant malpositioning.
      Unstable fracture patterns have to be identified and should be fixed using an
      appropriate technique, which include plating, K-wire fixation and arthroscopic
      techniques which bring the dislocated fragments into contact. Dislocated
      fractures of the acromion can usually be treated by plating.

PMID- 23007125
TI  - [Revision and salvage procedures for injuries to the acromioclavicular joint].
AB  - Failed conservative treatment or surgical procedures for acute AC joint
      seperations create the demand for revision or salvage procedures to successfully
      treat persistent AC joint instability. Besides the classic Weaver-Dunn procedure
      and its modifications lately new procedures combining a more or less rigid
      implant for primary stability with a biologic augmentation using an autologous
      tendon graft have been developed. These procedures are performed arthroscopically
      or arthroscopically assisted.

PMID- 23007126
TI  - [90 years of the German Society for Trauma Surgery: origins and foundation].

PMID- 23007128
TI  - Silica sol-gel glasses incorporating dual-luminescent Yb quinolinolato complex:
      processing, emission and photosensitising properties of the 'antenna' ligand.
AB  - The [Yb(5,7ClQ)(2)(H5,7ClQ)(2)Cl] (1) complex, that exhibits dual-luminescence in
      the visible (ligand-centered) and in the NIR (Yb-centered), has been incorporated
      into a silica sol-gel glass obtaining 1-doped glassy material which is optically
      transparent and homogeneous and with good mechanical properties. The doped sol
      gel glass can be considered a "solid state solution" and photophysical studies
      demonstrate that the emissive properties of the dopant complex are preserved in
      the silica matrix. Observed NIR decay times fall in the MUs range and are likely
      limited by "second-sphere" matrix interactions. The ligand-to-metal energy
      transfer mechanism occurs on ultrafast timescale and involves ligand triplet
      states. The sensitization efficiency of the antenna quinolinolato ligand toward
      Yb(3+) is estimated to be as high as ~80%. The Yb natural radiative lifetime
      observed for 1 in MeCN-EtOH solution (tau(rad) = 438 MUs) is the shortest
      reported so far for ytterbium complexes.

PMID- 23007127
TI  - [Value of cross-sectional imaging in posttraumatic low grade infection].
AB  - Regarding imaging diagnostics in case of posttraumatic or postoperative chronic
      osteomyelitis, x-ray should be the first choice to obtain basic information of
      the affected bone. Because knowledge of the exact dimensions of the inflammatory
      changes is essential for adequate therapy planning, diagnostics via cross
      sectional imaging is indicated in most cases. In order to adequately estimate the
      lesion's dimensions, magnetic resonance imaging (MRI) is the method of choice in
      these cases. Nuclear medicine examination techniques such as bone scintigraphy
      using specially marked granolocyte antibodies are alternatives to be considered
      for the evaluation of activated chronic osteomyelitis. CT exams are only rarely
      performed for the diagnosis of chronic osteomyelitis if a bone sequester can not
      be proven by either x-ray or MRI.

PMID- 23007129
TI  - Effects of ageing and staining on color of acrylic resin denture teeth.
AB  - OBJECTIVES: To assess the color stability of high-strength acrylic resin denture
      teeth after exposure to red wine, coffee and artificial ageing. METHODS: Four
      different shades of acrylic resin denture teeth were selected from three
      manufacturers. The teeth were evaluated in two phases: Phase I, upon staining for
      7 days in distilled water (control Group A), red wine (experimental Group B) and
      coffee (experimental Group C), and Phase II, upon artificial ageing in a Weather
      Ometer for a total exposure of 150 kJ/m(2) (control Group A; Phase I). Denture
      tooth positioning jigs were fabricated and color data recorded by means of an
      intra-oral spectrophotometer and expressed using the Commission Internationale
      d'Eclairage (CIE) L*a*b* color notation system. Means and standard deviations
      were determined. The staining data were analysed by three-way ANOVA, while the
      artificial ageing data were analysed by two-way ANOVA. Fisher's PLSD intervals
      were calculated at a significance level of P <= 0.05. RESULTS: In the staining
      experiment, the main effects of stains and denture teeth and the two-way and
      three-way interactions among stains, denture teeth and shades were significant (P
      <= 0.05). The same was true for the main effects of denture teeth and shades and
      their interactions in the ageing experiment. The smallest overall color change
      upon staining in red wine was recorded for Vita Physiodens denture teeth
      (DeltaE*=0.9 +/- 0.4), followed by SR Vivodent PE 1.2 (0.6) and Portrait IPN 2.4
      (0.6). Corresponding values for staining in coffee were 2.0 (0.6), 1.7 (1.0) and
      1.8 (0.8), while ageing-dependent changes in color were 1.7 (0.4), 2.4 (0.8) and
      1.1 (0.4) for Portrait IPN, SR Vivodent PE and Vita Physiodens teeth,
      respectively. CONCLUSION: Although the null hypothesis has been partially
      rejected, because some statistically significant changes in color and color
      coordinates occurred upon staining and ageing, all evaluated denture teeth
      exhibited good color stability compared to the 50:50% acceptability threshold
      used in data interpretation. CLINICAL SIGNIFICANCE: Selection of a color stable
      and stain-resistant denture tooth can contribute to denture longevity and overall
      patient satisfaction.

PMID- 23007130
TI  - Improvement in Psoriasis Area and Severity Index score predicts improvement in
      skin pain over time in patients with psoriasis.
AB  - Pain and discomfort are common and often severe skin symptoms in patients with
      psoriasis. However, no studies have investigated skin pain and discomfort over
      time, or factors that explain changes in these symptoms. The aims of the present
      study were to describe the changes in skin pain, skin discomfort and Psoriasis
      Area and Severity Index (PASI) over time, and to investigate whether change in
      PASI predicted change in skin pain intensity. A total of 129 patients
      participated in this exploratory, longitudinal study. Data were obtained through
      interviews and questionnaires. The results indicated reduction in skin symptoms
      and psoriasis severity over a period of 3 months. However, a majority of patients
      with skin pain at baseline reported also skin pain at follow-up. Furthermore,
      changes in PASI predicted changes in skin pain intensity. In conclusion,
      improvement in psoriasis severity predicts improvement in skin pain.

PMID- 23007131
TI  - Pulmonary imaging with a scanning acoustic microscope discriminates speed-of
      sound and shows structural characteristics of disease.
AB  - Tissue elasticity can be detected using a scanning acoustic microscope (SAM),
      whereby acoustic images are created from the speed of sound through tissues. This
      system discriminated pulmonary tissue components and demonstrated distinct
      acoustic images of the lung; these results corresponded well to those obtained
      using the conventional microscope. SAM provides the following benefits: (1)
      images are acquired in only few minutes without requirement for staining, (2)
      basic data is obtained for low-frequency ultrasonic examination, and (3) speed of
      sound from each lesion is digital and comparable among diseases. Comparative
      analysis of cancer invasion, post-inflammatory fibrosis, and deposition disease
      was possible using the data obtained with the system, and the results showed good
      correlation with those using the conventional microscope and by clinical
      diagnosis. The SAM system is applicable not only to pulmonary diseases but also
      to various diseases in other organs.

PMID- 23007132
TI  - Impairment of podocyte function by diphtheria toxin--a new reversible proteinuria
      model in mice.
AB  - Diphtheria toxin (DTx) receptor (DTR)-mediated conditional cell ablation in
      transgenic mice is a powerful tool to analyze cell function in vivo. Transgenic
      mice with cell-specific expression of the human DTR have been developed that
      allow conditional depletion of these cells in vivo through administration of the
      toxin. We have performed a careful analysis of mice after DTx injection and found
      an unexpected side effect. Treatment of wild-type C57BL/6 mice with DTx leads to
      a marked transient and completely reversible proteinuria, as a consequence of
      podocyte dysfunction that is morphologically characterized by foot process fusion
      and detachment from the glomerular basal membrane. In vitro analysis displayed
      that DTx-treated podocytes show diminished attachment to basal membrane proteins.
      Five to 9 days after DTx application the mice recover completely. Glomerular
      proteinuria is a hallmark of glomerular disease due to dysfunction of the
      filtration barrier. Rodents have been extensively used experimentally to better
      define the mechanisms of disease induction and progression. However, nongenetic
      mouse models of proteinuric glomerular damage are limited and display various
      shortcomings. We suggest DTx-induced transient kidney dysfunction as a new
      reversible model of experimental podocyte injury, which could be used as an
      additional approach to complement studies in human.

PMID- 23007133
TI  - The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in
      peritoneal dialysis-related epithelial-mesenchymal transition of peritoneal
      mesothelial cells.
AB  - Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs)
      has a role in the process of peritoneal fibrosis (PF), a serious complication in
      peritoneal dialysis (PD) patients. Even though monocyte chemoattractant protein-1
      (MCP-1) was demonstrated to directly increase extracellular matrix (ECM)
      synthesis, the role of the MCP-1/CCR2 system in PD-related EMT and ECM synthesis
      in cultured human PMCs (HPMCs) and in an animal model of PD has never been
      elucidated. In vitro, HPMCs were exposed to 5.6 mM glucose (NG), NG+MCP-1 (10
      ng/ml) (NG+MCP-1), or 100 mM glucose (HG) with or without CCR2 inhibitor
      (RS102895) (CCR2i) or a dominant-negative mutant MCP-1-expressing lentivirus (LV
      mMCP-1). In vivo, PD catheters were inserted into 60 Sprague-Dawley rats, and
      saline (Control, C) (N=30) or 4.25% PD solution (PD) (N=30) was infused for 4
      weeks. Twenty rats from each group were treated with empty LV or LV-mMCP-1
      intraperitoneally. Snail, E-cadherin, alpha-smooth muscle actin (alpha-SMA), and
      fibronectin protein expression in HPMCs and the peritoneum was evaluated by
      western blot analysis. Compared with NG cells, Snail, alpha-SMA, and fibronectin
      expression was significantly increased, while E-cadherin expression was
      significantly decreased in HPMCs exposed to HG and NG+MCP-1, and these changes
      were significantly abrogated by CCR2i (P<0.05). In addition, MCP-1-induced EMT
      was significantly attenuated by anti-TGF-beta1 antibody. In PD rats, Snail and
      fibronectin expression was significantly increased in the peritoneum, whereas the
      ratios of E-cadherin/alpha-SMA protein expression were significantly decreased
      (P<0.05). The thickness of the peritoneum and the intensity of Masson's trichrome
      staining in the peritoneum were also significantly higher in PD rats than in C
      rats (P<0.05). These changes in PD rats were significantly abrogated by LV-mMCP
      1. These findings suggest that the MCP-1/CCR2 system is directly involved in PD
      related EMT and ECM synthesis and that this is mediated, at least in part, via
      TGF-beta1.

PMID- 23007137
TI  - Comparison of active stretching technique in males with normal and limited
      hamstring flexibility.
AB  - OBJECTIVE: (1) to analyse the accumulative effects of a 12-week active stretching
      program on hip flexion passive range of motion (HF-PROM), and (2) to compare
      whether participants with different PROM baseline scores (normal and limited
      hamstring flexibility) respond in the same way to stretching. DESIGN: Repeated
      measures design. SETTING: Controlled laboratory environment. PARTICIPANTS: 138
      males were categorized according to hamstring flexibility in the unilateral
      passive straight-leg raise test (PSLR) and assigned to one of two groups: normal
      hamstring flexibility (>=80 degrees ) or limited hamstring flexibility (<80
      degrees ). In each group, participants were randomly distributed into one of two
      treatment subgroups: (a) control or (b) active stretching. The active stretching
      subgroups performed 12 weeks of flexibility training, the control subgroups did
      not stretch. MAIN OUTCOME MEASURES: HF-PROM was determined through the PSLR test.
      RESULTS: Both stretching subgroups significantly improved (p < 0.01) their HF
      PROM from baseline. The control subgroups did not. CONCLUSIONS: 12 weeks of an
      active stretching program performed 3 days per week with a daily stretch dose of
      180 s improved HF-PROM in both populations (normal and limited hamstring
      flexibility). The stretching program was equally effective in terms of absolute
      improvement values for males with normal and limited hamstring flexibility.

PMID- 23007134
TI  - Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic
      fibrosis.
AB  - Lumican, an extracellular matrix proteoglycan was previously shown to be
      upregulated with increasing severity of nonalcoholic steatohepatitis (NASH).
      Although lumican is involved in collagen fibrillogenesis in extra-hepatic
      tissues, little is known about the role of lumican in hepatic disease. We
      therefore determined lumican expression in etiologies other than clinical NASH.
      Our results indicated that lumican is upregulated in clinical samples of
      hepatitis C virus infection, in experimental rodent models of chronic and acute
      liver injury and could additionally be induced in vitro in response to the pro
      fibrotic cytokine transforming growth factor beta1 (TGFbeta1) and to lipotoxic
      palmitic acid. Together, these results suggested a role for lumican in hepatic
      fibrosis. To investigate the functional role of lumican in hepatic fibrosis,
      lumican null (Null) and wild-type (WT) littermates were administered carbon
      tetrachloride intra-peritoneally. Serum and liver tissue were analyzed for
      indices of liver injury, fibrosis, matrix turnover, and proliferation. Hepatic
      fibrosis was greatly reduced in null animals (P<0.05). Paradoxically, gene
      expression of fibrosis-related genes such as TGFbeta1 and collagen 1 was
      numerically higher in null animals though statistically insignificant from WT
      animals. On the other hand, alpha smooth muscle actin expression (alpha-SMA), a
      marker for activated fibroblasts, the main contributors of collagen production
      was significantly higher (P<0.05) in null animals as compared with WT
      littermates. Among the matrix metalloproteases (MMP), MMP13 was significantly
      increased (P<0.05) in null animals. Ultra-structural imaging indicated
      differences in the organization and spatial distribution of hepatic collagen
      fibrils of null and WT mice. Cell proliferation was significantly increased
      (P<0.05) in null animals. We conclude that lumican is a prerequisite for hepatic
      fibrosis. The protective effect of lumican deficiency in hepatic fibrosis appears
      to be downstream of collagen production and mediated through the combined effects
      of impaired collagen fibrillogenesis, increased matrix turnover, and an enhanced
      proliferative response.

PMID- 23007139
TI  - Myths of health care decentralization.
AB  - There are several myths about the impact of decentralization of health care
      governance. These include a worsening of regional inequalities, greater
      privatization of health care, greater inefficiency resulting from duplication of
      managerial activities such as human resource policies, and lower productivity.
      These myths have partly arisen from a lack of rigorous assessments of the effects
      of decentralization.

PMID- 23007138
TI  - Comparative study of human dental follicle cell sheets and periodontal ligament
      cell sheets for periodontal tissue regeneration.
AB  - Periodontal ligament cell (PDLC) sheets have been shown to contribute to
      periodontal tissue regeneration. Dental follicle cells (DFCs), acknowledged as
      the precursor cells of PDLCs, have demonstrated stemness, embryonic features,
      heterogeneity, and pluripotency. Therefore, we hypothesized that DFC sheets might
      be more effective and suitable for periodontal tissue regeneration than PDLC
      sheets. In this study, we compared the biological characteristics of DFC sheets
      and PDLC sheets in vitro. To investigate the potential for periodontal tissue
      regeneration in vivo, complexes composed of two types of cell sheets combined
      with dentin matrix were implanted subcutaneously into nude mice for 6 weeks. Our
      results showed that, when forming cell sheets, DFCs secreted richer extracellular
      matrix than PDLCs. And compared to DFCs, DFC sheets expressed high levels of
      calcification-related genes, including alkaline phosphatase (alp), bone
      sialoprotein (bsp), osteopontin (opn), runt-related transcription factor (runx2),
      as well as the periodontal ligament-specific genes collagen III (col III) and
      periostin, while the gene expression of bsp, osteocalcin (ocn), and opn were
      greatly increased in PDLC sheets, when compared to PDLCs. col I expression did
      not change significantly. However, cementum protein 23 (cp-23) expression
      increased several fold in PDLC sheets compared to PDLCs but decreased in DFC
      sheets compared to DFCs. DFC and PDLC sheets were both positive for Collagen I
      (Col I), cementum attachment protein (CAP), ALP, BSP, OCN, and OPN protein
      expression, and Col I, ALP, BSP, and OPN expression were increased after cell
      sheets were formed. Furthermore, the levels of laminin and fibronectin were
      higher in DFCs and DFC sheets than that of PDLCs and PDLC sheets, respectively.
      In vivo, DFC and PDLC sheets could both regenerate periodontal tissue-like
      structures, but DFC sheets demonstrated stronger periodontal regeneration
      potential than PDLC sheets. Therefore, DFC sheets derived from discarded dental
      follicle tissue after tooth extraction may be more advantageous for clinical
      periodontal tissue regeneration in the future.

PMID- 23007140
TI  - Clinical predictors of mortality and cause of death in lymphangioleiomyomatosis:
      a population-based registry.
AB  - PURPOSE: Lymphangioleiomyomatosis (LAM) is a rare, progressive, frequently lethal
      cystic lung disease that almost exclusively affects women. Prognostic information
      in LAM has been limited by small numbers and heterogeneous study methodology.
      Early retrospective cohorts cited 5- and 10-year mortality of 40 and 80 %,
      respectively. More recently, mortality at 10 years has been estimated to be
      approximately 10-20 % from the onset of symptoms and 30 % at 10 years from the
      time of lung biopsy but varies widely in individual patients. Given the
      heterogeneous disease course, it would be useful to establish which clinical
      characteristics are associated with survival to develop prediction models for
      disease outcome. METHODS: The LAM Foundation maintains a population-based
      registry of 1,149 registered self-identified LAM patients. Of these, 590 have
      completed a "General Information/Clinical History Questionnaire" with limited
      demographic and clinical data, 410 of whom were identified as U.S. residents and
      provided date of birth. Vital status was obtained on all 410 participants through
      December 31, 2007 by linking patient identifiers and the National Death Index.
      Survival time was calculated as the time since first lung-related symptom or
      physician diagnosis until censoring (still alive, received lung transplant, or
      died). Cox proportional hazard analysis evaluated the association of demographic
      and clinical features with survival. RESULTS: Among the 410 subjects, there were
      50 deaths and 55 lung transplantations during a median of 10.4 years of
      observation time. The estimated median transplant-free survival time for LAM
      patients in the United States is 29 years from symptom onset and 23 years from
      diagnosis. The estimated 10-year survival transplant-free was 86 %. Age at
      disease onset, smoking status, race, presence of tuberous sclerosis, occurrence
      of pneumothorax, and pregnancy did not demonstrate an association with survival
      or transplant. Greater age at presentation and presence of angiomyolipoma were
      associated with less risk of mortality. Treatment with hormonal therapy was
      associated with an increased risk of death/transplant (hazard ratio (HR) 2.93; 95
      % confidence interval (CI), 1.54-5.58; p = 0.001), particularly progesterone
      therapy (HR 2.17; 95 % CI 1.26-3.75, p = 0.005), and may represent confounding by
      indication. Patients who required oxygen therapy had a worse outcome (HR 4.53; 95
      % CI 2.76-7.42; p < 0.001). CONCLUSIONS: Our population-based study showed that
      the median survival in patients with LAM from the onset of symptoms or diagnosis
      is much longer than previously described. This has important implications for
      life choices and treatment decisions regarding medication use and lung
      transplantation for patients with LAM.

PMID- 23007141
TI  - Can implementation science help to overcome challenges in translating judicious
      antibiotic use into practice?

PMID- 23007143
TI  - Treatment options in anthracycline and/or taxane pretreated patients with
      metastatic breast cancer.

PMID- 23007142
TI  - Acute responses to intermittent and continuous exercise in heart failure
      patients.
AB  - BACKGROUND: The purpose of this study was to compare cardiopulmonary responses,
      exercise adherence, tolerance, and safety of optimized high-intensity interval
      exercise (HIIE) compared with moderate-intensity continuous exercise (MICE) in
      patients with heart failure and reduced ejection fraction (HFREF). METHODS:
      Twenty patients with HFREF (aged 61 +/- 9.9 years) were randomly assigned to HIIE
      corresponding to 2 * 8 minutes of 30-second intervals at 100% of peak power
      output and 30-second passive recovery intervals and to a 22-minute MICE
      corresponding to 60% of peak power output. Gas exchange, electrocardiogram, and
      blood pressure were measured continuously. Cardiac troponin T (cTnT), C-reactive
      protein (CRP), and brain natriuretic peptide (BNP) were measured before, 20
      minutes after, and 24 hours after HIIE and MICE. RESULTS: Cardiopulmonary
      responses did not differ between MICE and HIIE. Higher exercise adherence and
      efficiency were observed on HIIE with a similar perceived exertion and time spent
      above 90% of peak oxygen consumption compared with MICE. Neither HIIE nor MICE
      caused any significant arrhythmias or increased CRP, BNP, or cTnT. CONCLUSIONS:
      Compared with MICE, HIIE demonstrated a higher exercise adherence and was well
      tolerated in patients with HFREF, while still providing a high-level
      physiological stimulus and leaving indices of inflammation (CRP), myocardial
      dysfunction (BNP), and myocardial necrosis (cTnT) unaffected.

PMID- 23007144
TI  - Hepatic arterial infusion with irinotecan, oxaliplatin, and floxuridine plus
      systemic chemotherapy as first-line treatment of unresectable liver metastases
      from colorectal cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the therapeutic efficacy and
      safety of hepatic arterial infusion (HAI) with irinotecan, oxaliplatin, and
      floxuridine as a firstline treatment in patients with unresectable liver
      metastases of colorectal cancer (CRC). PATIENTS AND METHODS: Individual patients
      were treated with irinotecan (120 mg/m(2)), oxaliplatin (100 mg/m(2)), and
      floxuridine (500 mg/m(2)) via tumorsupplying arteries. Intravenous leucovorin
      (200 mg/day) and floxuridine (300 mg/m(2)/day) were given on days 1-3 after the
      procedure. The therapeutic courses were repeated every 4-8 weeks. Tumor
      responses, overall survival, and the time to tumor progression were observed.
      RESULTS: 204 cumulative cycles of chemotherapy were performed for 31 patients
      (median 7.0). 19 patients achieved a partial response; in 10 patients the disease
      stabilized, and in 2 patients the disease progressed, producing an overall
      response rate of 61.3%. The median survival time was 24.8 months, and the median
      time to tumor progression was 10.1 months. Frequencies of grade 3-4 neutropenia,
      diarrhea, elevation of serum bilirubin, elevation of serum transaminases, and
      vomiting were 6.5, 9.7, 3.2, 19.4, and 90.3%, respectively. CONCLUSION: This
      triplecombination chemotherapy as firstline treatment through HAI was well
      tolerated and effective in patients with unresectable liver metastases of CRC.

PMID- 23007145
TI  - Chronic graft versus host disease but not the intensity of conditioning has
      impact on survival after allogeneic hematopoietic stem cell transplantation for
      advanced hematological diseases.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is
      often performed in cases of advanced hematological diseases, but because of the
      associated mortality and a high risk of relapse it is life prolonging only in
      some patients. PATIENTS AND METHODS: A retrospective multi-center analysis of 401
      patients was conducted to analyze the variables associated with outcome after
      alloHSCT in advanced hematological diseases. The Cox proportional hazards model
      was used to assess the independence of overall survival (OS) and disease-free
      survival (DFS) from prognostic factors in a multivariate model. RESULTS: The 5
      year OS and DFS were 27.3 and 21.1% respectively. Multivariate analysis showed
      that the underlying malignancy had a significant influence on OS and DFS (p <
      0.001 and p < 0.011, respectively), whereas development of severe acute graft
      versus host disease (GvHD) had a negative impact on OS (p < 0.001). Development
      of chronic GvHD showed a trend to a better OS (p = 0.085) and DFS (p = 0.199). No
      impact was seen for the intensity of conditioning. CONCLUSION: Development of
      chronic GvHD but not the conditioning regimen improved the outcome after alloHSCT
      for advanced malignancies, underlining the importance of immunological rather
      than cytotoxic effects.

PMID- 23007146
TI  - Prognostic role of serum cytokines in patients with nasopharyngeal carcinoma.
AB  - BACKGROUND: Th1/Th2 cytokine network imbalance plays a major role in cancer
      development and progression. In this study, we aim to evaluate the relationship
      between those cytokines and clinical outcome in patients with nasopharyngeal
      carcinoma (NPC). PATIENTS AND METHODS: The concentrations of Th1 cytokines (IL-2,
      TNF-alpha, IFN-gamma) and Th2 cytokines (IL-4, IL-5, IL-10) in the serum were
      examined by Cytometric Bead Array in a total of 80 nasopharyngeal carcinoma
      patients pre and post treatment. Associations of those cytokines with clinical
      pathological factors, treatment response, and overall survival were analyzed.
      RESULTS: Pretreatment serum levels of IL-2 and TNF-alpha were closely associated
      with overall survival. Compared to patients with low IL-2 expression, those with
      high expression had less risk of death (hazard ratio (HR) = 0.31, 95% confidence
      interval (CI) 0.13-0.75, p = 0.009). In contrast, TNF-alpha showed opposite
      effects on overall survival in patients with NPC. Patients with high TNF-alpha
      expression had a more than 2-fold increase in risk of death than those with low
      TNF-alpha (HR = 2.66, 95% CI 1.04-6.78, p = 0.041). All HRs were adjusted for
      age, sex, stage, histology, and treatment. Kaplan-Meier survival analysis showed
      similar survival differences between the 2 groups. CONCLUSION: Lower serum IL-2
      or elevated serum TNF-alpha concentrations predict an unfavorable prognosis for
      patients with NPC.

PMID- 23007147
TI  - Mitomycin C in combination with vinorelbine in anthracycline- and/or taxane
      pretreated patients with metastatic breast cancer.
AB  - BACKGROUND: Patients with metastatic breast cancer (MBC) with disease progression
      after anthracycline-and/or taxane-containing therapy need an effective drug
      regimen with low toxicity. Mitomycin C (MMC) and vinorelbine (VNR) are suitable
      candidates for combination therapy in the second-/third-line treatment of MBC.
      This study evaluates the safety and efficacy of an MMC/VNR combination
      chemotherapy in pretreated patients with MBC. PATIENTS AND METHODS: In a phase II
      trial, patients with anthracycline-and/or taxane-pretreated MBC were treated with
      MMC 8 mg/m(2) (day 1) and VNR 25 mg/m(2) (days 1 and 8) every 4 weeks for up to 6
      cycles or until disease progression. RESULTS: In 51 eligible patients, 13 (26%)
      partial remissions (PRs), 20 (39%) stable diseases (SDs) and 18 (35%) progressive
      diseases (PDs) were observed. The median progression-free survival (PFS) was 5.0
      months. The main grade 3/4 toxicities were neutrocytopenia (41%),
      granulocytopenia (37%), and thrombocytopenia (4%). Other hematological and non
      hematological toxicities were mostly mild. CONCLUSION: The combination of MMC and
      VNR is an effective and relatively well-tolerated regimen for anthracycline-
      and/or taxane-pretreated patients with MBC and is suitable for outpatient
      therapy.

PMID- 23007148
TI  - Combination of trastuzumab and triple FLOT chemotherapy (5
      fluorouracil/leucovorin, oxaliplatin, and docetaxel) in patients with HER2
      positive metastatic gastric cancer: report of 3 cases.
AB  - BACKGROUND: Trastuzumab in combination with doublet chemotherapy (cisplatin and
      fluoropyrimidine) is a standard treatment for patients with HER2-positive
      advanced gastric cancer. There have been no studies evaluating trastuzumab with
      more intensive triplet chemotherapy regimens in this setting. We report the
      treatment outcome in 3 patients with HER2-positive metastatic gastric cancer who
      were treated with trastuzumab plus the triplet FLOT regimen (5
      fluorouracil/leucovorin, oxaliplatin, and docetaxel). PATIENTS AND METHODS: 3
      patients with HER2-positive metastatic gastric cancer received trastuzumab plus
      FLOT. Trastuzumab 4 mg/kg was given with the 2nd chemotherapy cycle and was
      continued at 2 mg/kg every week with subsequent cycles. RESULTS: All 3 patients
      had a dismal prognosis because of their heavy disease burden, most notably
      extensive hepatic metastatic involvement. Patients tolerated the triple-drug plus
      trastuzumab combination well. All patients exhibited a dramatic clinical
      response. CONCLUSION: This report provides the first evidence that the addition
      of trastuzumab to a docetaxel-based, triple-drug chemotherapy combination is
      feasible and highly active in patients with HER2-positive metastatic gastric
      cancer.

PMID- 23007149
TI  - Gefitinib-induced hepatotoxicity in patients treated for non-small cell lung
      cancer.
AB  - BACKGROUND: Although epidermal growth factor receptor (EGFR)-specific tyrosine
      kinase inhibitors (TKIs) are widely used in the management of advanced non-small
      cell lung cancer (NSCLC), gefitinib-induced hepatotoxicity has been
      underappreciated and rarely reported. CASE REPORT: The medical records of 92
      NSCLC patients, who were admitted to our cancer center in the past 5 years, were
      reviewed retrospectively. All patients received treatment with gefitinib (250
      mg/day), during which liver function was monitored. Of the 92 NSCLC patients, 6
      (6.5%) developed mild to moderate hepatotoxicity during gefitinib treatment. The
      time of onset of hepatotoxicity ranged from 7 days to 6 months after gefitinib
      administration. 1 patient (1.1%) suffered from grade 2 hepatotoxicity, and
      gradually recovered her normal liver function after reduction of the gefitinib
      dose. The other 5 patients with grade 1 hepatic impairment tolerated gefitinib
      well without requiring dose reductions or drug cessation. CONCLUSION: Gefitinib
      induced hepatotoxicity is not uncommon. Although the extent of this toxicity is
      generally mild in nature and most patients tolerate gefitinib well, meticulous
      monitoring is mandatory to avoid severe hepatic impairment.

PMID- 23007150
TI  - Sorafenib-induced tuberculosis reactivation.
AB  - BACKGROUND: Sorafenib is a multikinase inhibitor with an established role in
      treating renal cell carcinoma and hepatocellular carcinoma. In vivo studies have
      demonstrated sorafenib's inhibitory effects on various immune cells and cytokines
      which are essential to the maintenance of latency of granulomas in patients with
      latent tuberculosis infection. CASE REPORT: A 74-year-old male with clear cell
      renal cell carcinoma with pulmonary metastases was treated with sorafenib to good
      effect. However, he developed productive cough, sweats and weight loss. A
      computed tomography scan of the thorax demonstrated right lower lobe
      consolidation and cavitation. Sputum analysis was positive for tuberculous smear
      and culture. A diagnosis of sorafenib-induced tuberculosis reactivation was made.
      Sorafenib was held and anti-tuberculous antibiotics were commenced, which led to
      symptomatic and radiographic improvement. CONCLUSION: The authors postulate that
      sorafenib could increase the risk of progression from latent to active
      tuberculosis, and urge vigilance and possible screening for latent tuberculosis
      in patients who are treated with sorafenib.

PMID- 23007151
TI  - A pregnant patient with adrenocortical carcinoma: case report.
AB  - BACKGROUND: Coexistence of an adrenocortical carcinoma and pregnancy is extremely
      rare with only 25 described cases so far, and has a poor prognosis. CASE REPORT:
      We report the case of a 28-year-old patient with adrenocortical carcinoma
      initially presenting with Cushing's syndrome and pre-eclampsia in the 22nd week
      of gestation, treated in our department. She underwent adrenalectomy, but
      eventually died from metastatic disease. We focus on existing treatment options
      and concerns for this rare malignancy during pregnancy. CONCLUSION: Early
      diagnosis and surgery are the cornerstones for better outcome.

PMID- 23007152
TI  - Low rates of influenza vaccination among hematologic patients and their household
      contacts.

PMID- 23007153
TI  - Role of imaging methods in metastatic melanoma.
AB  - Melanoma is a malignant neoplasm of the skin deriving from melanocytes.
      Accounting for less than 5% of all skin cancers, melanoma is associated with
      approximately 75% of skin cancer-related mortality. Early detection of melanoma
      with surgical resection remains one of the critical factors determining favorable
      clinical outcomes for melanoma. Up to now, many imaging methods, such as
      ultrasound, computed tomography (CT), magnetic resonance imaging, and positron
      emission tomography/CT, have been used in the diagnosis of melanoma and
      metastases. This article reviews the application of imaging methods in metastatic
      melanoma.

PMID- 23007155
TI  - The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end
      resection and checkpoint deactivation.
AB  - Fun30 is a Swi2/Snf2 homolog in budding yeast that has been shown to remodel
      chromatin both in vitro and in vivo. We report that Fun30 plays a key role in
      homologous recombination, by facilitating 5'-to-3' resection of double-strand
      break (DSB) ends, apparently by facilitating exonuclease digestion of nucleosome
      bound DNA adjacent to the DSB. Fun30 is recruited to an HO endonuclease-induced
      DSB and acts in both the Exo1-dependent and Sgs1-dependent resection pathways.
      Deletion of FUN30 slows the rate of 5'-to-3' resection from 4 kb/h to about 1.2
      kb/h. We also found that the resection rate is reduced by DNA damage-induced
      phosphorylation of histone H2A-S129 (gamma-H2AX) and that Fun30 interacts
      preferentially with nucleosomes in which H2A-S129 is not phosphorylated. Fun30 is
      not required for later steps in homologous recombination. Like its homolog
      Rdh54/Tid1, Fun30 is required to allow the adaptation of DNA damage checkpoint
      arrested cells with an unrepaired DSB to resume cell cycle progression.

PMID- 23007156
TI  - The minimal active human SVA retrotransposon requires only the 5'-hexamer and Alu
      like domains.
AB  - RNA-based duplication mediated by reverse transcriptase (RT), a process termed
      retrotransposition, is ongoing in humans and is a source of significant inter-
      and perhaps intraindividual genomic variation. The long interspersed element 1
      (LINE-1 or L1) ORF2 protein is the genomic source for RT activity required for
      mobilization of its own RNA in cis and other RNAs, such as SINE/variable-number
      tandem-repeat (VNTR)/Alu (SVA) elements, in trans. SVA elements are ~2-kb hominid
      specific noncoding RNAs that have resulted in single-gene disease in humans
      through insertional mutagenesis or aberrant mRNA splicing. Here, using an SVA
      retrotransposition cell culture assay in U2OS cells, we investigated SVA domains
      important in L1-mediated SVA retrotransposition. Partial- and whole-domain
      deletions revealed that removal of either the Alu-like or SINE-R domain in the
      context of a full-length SVA has little to no effect, whereas removal of the CT
      hexamer or the VNTR domain can result in a 75% decrease in activity. Additional
      experiments demonstrate that the Alu-like fragment alone can retrotranspose at
      low levels while the addition of the CT hexamer can enhance activity as much as 2
      fold compared to that of the full-length SVA. These results suggest that no SVA
      domain is essential for retrotransposition in U2OS cells and that the 5' end of
      SVA (hexamer and Alu-like domain) is sufficient for retrotransposition.

PMID- 23007157
TI  - IkappaB kinase epsilon phosphorylates TRAF2 to promote mammary epithelial cell
      transformation.
AB  - NF-kappaB transcription factors are central regulators of inflammation and when
      dysregulated contribute to malignant transformation. IkappaB kinase epsilon
      (IKKepsilon; IKKi, encoded by IKBKE) is a breast oncogene that is amplified in
      30% of breast cancers and drives transformation in an NF-kappaB-dependent manner.
      Here we demonstrate that IKKepsilon interacts with and phosphorylates tumor
      necrosis factor receptor-associated factor 2 (TRAF2) at Ser11 in vitro and in
      vivo. This activity promotes Lys63-linked TRAF2 ubiquitination and NF-kappaB
      activation and is essential for IKKepsilon transformation. Breast cancer cells
      that depend on IKKepsilon expression for survival are also dependent on TRAF2.
      This work defines TRAF2 phosphorylation to be one key effector of IKKepsilon
      induced mammary epithelial cell transformation.

PMID- 23007158
TI  - Ribosome-associated complex and Ssb are required for translational repression
      induced by polylysine segments within nascent chains.
AB  - When a polyadenylated nonstop transcript is fully translated, a complex
      consisting of the ribosome, the nonstop mRNA, and the C-terminally polylysine
      tagged protein is generated. In Saccharomyces cerevisiae, a 3-step quality
      control system prevents formation of such dead-end complexes. Nonstop mRNA is
      rapidly degraded, translation of nonstop mRNA is repressed, and finally, nonstop
      proteins are cotranslationally degraded. Nonstop mRNA degradation depends on Ski7
      and the exosome; nonstop protein degradation depends on the ribosome-bound E3
      ligase Ltn1 and the proteasome. However, components which mediate translational
      repression of nonstop mRNA have previously not been identified. Here we show that
      the ribosome-bound chaperone system consisting of the ribosome-associated complex
      (RAC) and the Hsp70 homolog Ssb is required to stabilize translationally
      repressed ribosome-polylysine protein complexes, without affecting the folding or
      the degradation of polylysine proteins. As a consequence, in the absence of
      RAC/Ssb, polylysine proteins escaped translational repression and subsequently
      folded into their native conformation. This active role of RAC/Ssb in the quality
      control of polylysine proteins significantly contributed to the low level of
      expression of nonstop transcripts in vivo.

PMID- 23007160
TI  - Trait impulsivity is increased in bipolar disorder patients with comorbid alcohol
      use disorders.
AB  - BACKGROUND: Up to 60% of bipolar disorder (BD) patients develop alcohol use
      disorders (AUD) at some point in their lives. The causes of this highly prevalent
      comorbidity are unknown. High trait impulsivity characterizes both isolated BD
      and AUD and may be a link to explain the association between BD and AUD. In this
      study, our aims were to investigate whether BD patients with comorbid AUD would
      present higher trait impulsivity levels compared to BD patients without comorbid
      AUD, and whether trait impulsivity levels differ within subgroups of BD according
      to the subcategory of AUD (abuse vs. dependence, alcoholism alone vs. alcoholism
      plus drug use disorders). SAMPLING AND METHODS: Forty-seven outpatients with BD
      with comorbid AUD (alcoholic BD group) were compared to 66 outpatients with BD
      alone (nonalcoholic BD group) and to 90 healthy controls (HC). BD and AUD
      diagnoses were obtained using the Structured Clinical Interview for DSM-IV
      diagnoses. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS
      11), a self-report instrument that measures trait impulsivity in three domains:
      nonplanning, attentional and motor. RESULTS: Alcoholic BD patients scored
      significantly higher than nonalcoholic BD and HC on the total and on each
      subscale BIS scores. Within the alcoholic BD patients, alcohol abusers and
      alcohol dependents did not statistically differ from each other on the BIS-11
      scores. BD patients with AUD plus drug use disorders presented statistically
      higher nonplanning impulsivity than BD patients with AUD alone. CONCLUSIONS: This
      was a cross-sectional study and causal inferences about the relationship between
      impulsivity and the comorbidity phenomenon cannot be made. Increased impulsivity
      may be a trait marker for the co-occurrence between BD and AUD, and mediate some
      severe manifestations of this comorbidity.

PMID- 23007161
TI  - Comparison of the Icare tonometer and the hand-held goldmann applanation
      tonometer in pediatric aphakia.
AB  - PURPOSE: To compare the intraocular pressure (IOP) measurements obtained by the
      Icare and the hand-held Goldmann applanation tonometer (also called Perkins) in
      aphakic children after congenital cataract surgery. METHODS: We investigated 125
      children with aphakia after congenital cataract surgery in this study. A younger
      group (3 to 30 mo) and an elder group (31 to 72 mo) were divided in those
      patients by their age. In the younger group, all measurements were performed
      under sedation using chloral hydrate. Axial length of the eye and central corneal
      thickness (CCT) were also measured from all patients. RESULTS: Significant
      correlation was found on IOP readings obtained by the Icare and the Perkins
      tonometers (r=0.943, P<0.001). After establishing a Bland-Altman plot, we found
      that 95% limit of the agreement between the 2 methods distributed between -1.6 to
      5.6 mm Hg. The IOPs recorded from the Icare increased faster than that from the
      Perkins tonometer with the increase of the CCT thickness; a significant
      association relationship was found on the IOP difference between the 2
      measurements (r=0.408, P<0.001). However, no statistical correlation was
      identified between the axial length and the IOPs recorded by either tonometer.
      CONCLUSIONS: Most of the young patients accepted the Icare tonometer under
      unsedated conditions. This significant advantage indicated that the Icare
      tonometer will be overall better tolerated in pediatric aphakia population,
      although it could overestimate the IOPs compared with the measurements obtained
      from the Perkins tonometer. Differences in readings between the 2 tonometers
      become bigger as the CCT increase.

PMID- 23007162
TI  - Photolytic water oxidation catalyzed by a molecular carbene iridium complex.
AB  - The complex IrCl(2)(Cp*)(trz) (trz = triazolylidene), 2, was prepared from
      readily available 1,3-dimethyl-4-phenyl-1,2,3-triazolium salt. Under basic
      conditions, the C-bound phenyl group readily cyclometalates, while under acidic
      conditions, cyclometalation is reversed. The sensitivity of the C(aryl)-Ir bond
      but not the C(trz)-Ir bond towards acidolysis provided a basis for using 2 as a
      catalyst in Ce(IV)-mediated water oxidation. The catalytic activity is
      characterized by a robust catalytic cycle, affording excellent turnover numbers
      (TON > 20,000). Under cerium-free conditions and in the presence of hematite as a
      photoelectrode, light-induced activity was observed. The photoelectrochemical
      reaction is strongly pH-dependent, which requires pH adjustments when running
      multiple cycle experiments to regenerate the catalytic activity. Analogous
      chelating complexes display better stability and higher catalytic activity than
      the monodentate complex 2.

PMID- 23007159
TI  - Transition step during assembly of HIV Tat:P-TEFb transcription complexes and
      transfer to TAR RNA.
AB  - Transcription factors regulate eukaryotic RNA polymerase II (Pol II) activity by
      assembling and remodeling complexes at multiple steps in the transcription cycle.
      In HIV, we previously proposed a two-step model where the viral Tat protein first
      preassembles at the promoter with an inactive P-TEFb:7SK snRNP complex and later
      transfers P-TEFb to TAR on the nascent transcript, displacing the inhibitory
      snRNP and resulting in Pol II phosphorylation and stimulation of elongation. It
      is unknown how the Tat:P-TEFb complex transitions to TAR to activate the P-TEFb
      kinase. Here, we show that P-TEFb artificially recruited to the nascent
      transcript is not competent for transcription but rather remains inactive due to
      its assembly with the 7SK snRNP. Tat supplied in trans is able to displace the
      kinase inhibitor Hexim1 from the snRNP and activate P-TEFb, thereby uncoupling
      Tat requirements for kinase activation and TAR binding. By combining
      comprehensive mutagenesis of Tat with multiple cell-based reporter assays that
      probe the activity of Tat in different arrangements, we genetically defined a
      transition step in which preassembled Tat:P-TEFb complexes switch to TAR. We
      propose that a conserved network of residues in Tat has evolved to control this
      transition and thereby switch the host elongation machinery to viral
      transcription.

PMID- 23007163
TI  - Decreased miR-7 expression in the skin and sera of patients with dermatomyositis.
AB  - Expression of microRNA (miRNA) in the skin in dermatomyositis has not previously
      been studied in detail. In this study, we performed miRNA array analysis using
      miRNAs purified from dermatomyositis-involved skin and normal skin, and found
      that several miRNAs were up- or down-regulated in dermatomyositis skin. Among
      them, we focused on miR-7, one of the most down-regulated miRNAs in
      dermatomyositis skin. Total miRNAs were purified from serum, and hsa-miR-7 levels
      were measured with quantitative real-time PCR using the specific primer. Serum
      levels of miR-7 were significantly decreased in patients with dermatomyositis
      compared with normal subjects or patients with other autoimmune diseases. Thus,
      serum miR-7 levels might be a possible diagnostic marker for dermatomyositis.
      Clarifying the up- or down-stream events of down-regulated miR-7 in patients with
      dermatomyositis may lead to further understanding of the disease and a new
      therapeutic approach.

PMID- 23007164
TI  - Cochlear implantation in the elderly.
AB  - OBJECTIVES: To analyse complications and outcome of cochlear implant (CI)
      treatment in seniors receiving CIs during a 10-year period. METHODS: A total of
      28 patients, 79 years or older (mean age 81.6 years), were evaluated and compared
      with a younger group of 76 patients, 20-60 years old (mean age 48.9 years). A
      retrospective study of the patients' records was performed. Data on per- and post
      operative complications, pre- and post-operative speech perception, estimated
      cognitive skills, and social situation was extracted. A subjective score was
      assessed and correlated with post-operative performance. RESULTS: No severe per-
      or post-operative surgical complications were noted. Speech perception improved
      significantly after surgery (P < 0.001). The younger age group showed better
      results post-operatively for monosyllabic words (P < 0.01) compared with the
      older group with no difference seen for bi-syllabic words. In both the groups,
      there were no significant differences between patients living with or without
      social support. DISCUSSION: CI surgery for patients 79 years or older was well
      tolerated. Patients benefited greatly from the device with improved hearing. CI
      should not be denied older individuals who are otherwise in good health. Non-use
      in the elderly was associated with post-operative vertigo and tinnitus, severe
      disease and limited social support.

PMID- 23007165
TI  - A proteomic Ramachandran plot (PRplot).
AB  - Each protein structure can be characterized by the average values of the main
      chain torsion angles phi and psi and, as a consequence, be plotted on a
      bidimensional diagram, which resembles the Ramachandran plot. Here, we describe a
      proteomic phi-psi plot (PRplot) where each protein structure is associated with
      one point, allowing in this way to represent the entire protein structure
      universe. It was verified that the PRplot is a robust tool since it does not
      depend on the dimension of the proteins, on the crystallographic resolution of
      the structures, nor on the biological source; moreover, it is little affected by
      disordered and structurally uncharacterized residues. The proteins mapped on the
      PRplot tend to cluster in three regions that correspond to the structures rich in
      alpha-helices, in beta-strands, and in both helices and strands, and are
      distributed along a sigmoidal curve that connect these three highly populated
      regions. PRplots are a unique instrument to project all protein structures on a
      single bidimensional plane where the entire structural complexity is reduced to a
      striking simplicity, with the sigmoid curve clearly delineating the space
      fraction accessible to a stable protein.

PMID- 23007166
TI  - Association between elevated plasma fibrinogen and psychological distress, and
      depression in 73,367 individuals from the general population.

PMID- 23007167
TI  - Lack of brain serotonin affects postnatal development and serotonergic neuronal
      circuitry formation.
AB  - Despite increasing evidence suggests that serotonin (5-HT) can influence
      neurogenesis, neuronal migration and circuitry formation, the precise role of 5
      HT on central nervous system (CNS) development is only beginning to be
      elucidated. Moreover, how changes in serotonin homeostasis during critical
      developmental periods may have etiological relevance to human mental disorders,
      remains an unsolved question. In this study we address the consequences of 5-HT
      synthesis abrogation on CNS development using a knock-in mouse line in which the
      tryptophan hydroxylase 2 (Tph2) gene is replaced by the eGFP reporter. We report
      that lack of brain 5-HT results in a dramatic reduction of body growth rate and
      in 60% lethality within the first 3 weeks after birth, with no gross anatomical
      changes in the brain. Thanks to the specific expression of the eGFP, we could
      highlight the serotonergic system independently of 5-HT immunoreactivity. We
      found that lack of central serotonin produces severe abnormalities in the
      serotonergic circuitry formation with a brain region- and time- specific effect.
      Indeed, we observed a striking reduction of serotonergic innervation to the
      suprachiasmatic and thalamic paraventricular nuclei, while a marked serotonergic
      hyperinnervation was found in the nucleus accumbens and hippocampus of Tph2?eGFP
      mutants. Finally, we demonstrated that BDNF expression is significantly up
      regulated in the hippocampus of mice lacking brain 5-HT, mirroring the timing of
      the appearance of hyperinnervation and thus unmasking a possible regulatory
      feedback mechanism tuning the serotonergic neuronal circuitry formation. On the
      whole, these findings reveal that alterations of serotonin levels during CNS
      development affect the proper wiring of the brain that may produce long-lasting
      changes leading to neurodevelopmental disorders. 

PMID- 23007169
TI  - The metabolic syndrome of fructose-fed rats: effects of long-chain
      polyunsaturated omega3 and omega6 fatty acids. VI. Further post-mortem
      investigations.
AB  - The present study documents the increases in systolic arterial blood pressure,
      plasma leptin concentration and kidney proliferating cell nuclear antigen index,
      as well as the decreases in glutathione reductase, superoxide dismutase and
      catalase enzymatic activities in the liver, heart, kidney, soleus muscle and
      visceral adipose tissue homogenates of female rats exposed for 8 weeks to a diet
      containing 64% (w/w) D-fructose instead of 64% starch. In the fructose-fed rats,
      the partial substitution of sunflower oil by either safflower oil or salmon oil
      often opposed the fructose-induced changes in these variables. The present
      results, thus, extend to these functional, hormonal and enzymatic parameters the
      knowledge that the dietary supply of long-chain polyunsaturated omega6 fatty
      acids, mainly C18:2omega6, and long-chain polyunsaturated omega3 fatty acids
      opposes the undesirable features of the fructose-induced metabolic syndrome, with
      salmon oil demonstrating particular efficacy.

PMID- 23007170
TI  - In situ EDXRD study of the chemistry of aging of co-precipitated mixed Cu,Zn
      hydroxycarbonates--consequences for the preparation of Cu/ZnO catalysts.
AB  - In order to better understand the critical influence of the synthesis parameters
      during preparation of Cu/ZnO catalysts at the early stages of preparation, the
      aging process of mixed Cu,Zn hydroxide carbonate precursors was decoupled from
      the precipitation and studied independently under different conditions, i.e.
      variations in pH, temperature and additives, using in situ energy-dispersive XRD
      and in situ UV-Vis spectroscopy. Crystalline zincian malachite, the relevant
      precursor phase for industrial catalysts, was formed from the amorphous starting
      material in all experiments under controlled conditions by aging in solutions of
      similar composition to the mother liquor. The efficient incorporation of Zn into
      zincian malachite can be seen as the key to Cu/ZnO catalyst synthesis. Two
      pathways were observed: direct co-condensation of Cu(2+) and Zn(2+) into Zn-rich
      malachite at 5 >= pH >= 6.5, or simultaneous initial crystallization of Cu-rich
      malachite and a transient Zn-storage phase. This intermediate re-dissolved and
      allowed for enrichment of Zn into malachite at pH >= 7 at later stages of solid
      formation. The former mechanism generally yielded a higher Zn-incorporation. On
      the basis of these results, the effects of synthesis parameters like temperature
      and acidity are discussed and their effects on the final Cu/ZnO catalyst can be
      rationalized.

PMID- 23007171
TI  - Geographic variation in outpatient antibiotic prescribing among older adults.
AB  - BACKGROUND: Consequences of antibiotic overuse are substantial, especially among
      older adults, who are more susceptible to adverse reactions. Findings about
      variation in antibiotic prescribing can target policy efforts to focused areas;
      however, little is known about these patterns among older adults. METHODS: Using
      Medicare Part D data from January 1, 2007, through December 31, 2009 (comprising
      1.0-1.1 million patients per year), we examined geographic variation in
      antibiotic use among older adults in 306 Dartmouth Atlas of Health Care hospital
      referral regions, 50 states and the District of Columbia, and 4 national regions
      (South, West, Midwest, and Northeast). In addition, we examined the quarterly
      change in antibiotic use across the 4 regions. Differences in patient
      demographics, insurance status, and clinical characteristics were adjusted for
      across regions. RESULTS: Substantial geographic and quarterly variation in
      outpatient antibiotic prescribing existed across regions after adjusting for
      population characteristics. This variation could not be explained by differences
      in the prevalences of the underlying conditions. For example, the ratios of the
      75th percentile to the 25th percentile of adjusted annual antibiotic spending
      were 1.31 across states and 1.32 across regions. The highest antibiotic use was
      in the South, where 21.4% of patients per quarter used an antibiotic, whereas the
      lowest antibiotic use was in the West, where 17.4% of patients per quarter used
      an antibiotic (P < .01). Regardless of region, the rate of antibiotic use was
      highest in the first quarter (20.9% in January through March) and was lowest in
      the third quarter (16.9% in July through September) (P < .01). CONCLUSIONS: Areas
      with high rates of antibiotic use may benefit from targeted programs to reduce
      unnecessary prescription. Quality improvement programs can set attainable targets
      using the low-prescribing areas as a reference, particularly targeting older
      adults.

PMID- 23007172
TI  - Power and phase properties of oscillatory neural responses in the presence of
      background activity.
AB  - Natural sensory inputs, such as speech and music, are often rhythmic. Recent
      studies have consistently demonstrated that these rhythmic stimuli cause the
      phase of oscillatory, i.e. rhythmic, neural activity, recorded as local field
      potential (LFP), electroencephalography (EEG) or magnetoencephalography (MEG), to
      synchronize with the stimulus. This phase synchronization, when not accompanied
      by any increase of response power, has been hypothesized to be the result of
      phase resetting of ongoing, spontaneous, neural oscillations measurable by LFP,
      EEG, or MEG. In this article, however, we argue that this same phenomenon can be
      easily explained without any phase resetting, and where the stimulus-synchronized
      activity is generated independently of background neural oscillations. It is
      demonstrated with a simple (but general) stochastic model that, purely due to
      statistical properties, phase synchronization, as measured by 'inter-trial phase
      coherence', is much more sensitive to stimulus-synchronized neural activity than
      is power. These results question the usefulness of analyzing the power and phase
      of stimulus-synchronized activity as separate and complementary measures;
      particularly in the case of attempting to demonstrate whether stimulus
      synchronized neural activity is generated by phase resetting of ongoing neural
      oscillations.

PMID- 23007173
TI  - Ethical genetic research in Indigenous communities: challenges and successful
      approaches.
AB  - Indigenous populations, in common with all populations, stand to benefit from the
      potential of genetic research to lead to improvements in diagnostic and
      therapeutic tools for a wide range of complex diseases. However, many Indigenous
      communities, especially ones that are isolated, are not included in genetic
      research efforts. This situation is largely a consequence of the challenges of
      ethically conducting genetic research in Indigenous communities and compounded by
      Indigenous peoples' negative past experiences with genetic issues. To examine
      ways of addressing these challenges, we review one investigation of a cancer
      cluster in remote Aboriginal communities in Arnhem Land, Australia. Our
      experiences demonstrate that genetic research can be both ethically and
      successfully conducted with Indigenous communities by respecting the authority of
      the community, involving community members, and including regular community
      review throughout the research process.

PMID- 23007174
TI  - Vanillin suppresses Kupffer cell-related colloidal carbon-induced respiratory
      burst activity in isolated perfused rat liver: anti-inflammatory implications.
AB  - The inhibition of NADPH oxidase has become a potential therapeutic target for
      oxidative stress-related diseases. We investigated whether vanillin modifies
      hepatic O(2) consumption associated with Kupffer cell functioning. The influence
      of vanillin on Kupffer cell functioning was studied in isolated perfused rat
      liver by colloidal carbon (CC) infusion (0.5 mg ml(-1)), concomitantly with
      sinusoidal efflux of lactate dehydrogenase (LDH) as an organ viability parameter.
      CC infusion increased the rate of O(2) consumption of the liver above basal
      values, an effect that represents the respiratory burst activity of Kupffer
      cells. However, CC-dependent respiratory burst activity was suppressed by
      previous infusion of 2 mM vanillin. Vanillin did not affect the liver CC uptake
      rate and liver sinusoidal efflux of LDH efflux. These findings, elicited by
      vanillin, were reproduced by the well-established NADPH oxidase inhibitor
      apocynin. In conclusion, vanillin suppresses the respiratory burst activity of
      Kupffer cells as assessed in intact liver, which may be associated with the
      inhibition of macrophage NADPH oxidase activity. Such a finding may have
      relevance in conditions underlying Kupffer cell-dependent up-regulation of the
      expression and release of pro-inflammatory mediators by redox-dependent
      mechanisms.

PMID- 23007175
TI  - Development of an indirect competitive enzyme-linked immunosorbent assay
      (icELISA) using highly specific monoclonal antibody against paclitaxel.
AB  - Paclitaxel, the major active component of the yew tree, is used as an important
      anti-cancer agent. To obtain the monoclonal antibody (MAb) against paclitaxel for
      paclitaxel determination using immunoassay, 7-xylosyltaxol was conjugated to the
      carrier protein bovine serum albumin (BSA) to construct the immunogen, and the
      ratio of hapten in XylTax-BSA conjugate was determined by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. After immunization of
      mice with this conjugate, hybridomas secreting MAbs against paclitaxel were
      obtained by fusing the splenocytes with the mouse myeloma cell line SP2/0. After
      hybridoma screening, the anti-paclitaxel MAb 3A3 was obtained, which showed a
      relatively high specificity to paclitaxel (cross-reactivities against other
      naturally occurred taxanes: 7-xylosyltaxol, 31.8%; cephalomannine, 6.17%;
      baccatin III, 10-deacetyl-baccatin III, 1-hydroxybaccatin I, 13-acetyl-9
      dihydrobaccatin III and 1-acetoxyl-5-deacetyl-baccatin I, <0.11%). Using the MAb
      3A3, we established an indirect competitive enzyme-linked immunosorbent assay
      (icELISA) for paclitaxel determination with a detection range of 0.098-312.5 MUg
      ml(-1). Determination of paclitaxel contents in various yew tree samples with
      this icELISA resulted in recovery rates ranging from 92 to 94.8%, and intra- and
      inter-assay variations of 3.6 and 4.7%, respectively. This icELISA provides a
      valuable method of paclitaxel determination for various purposes.

PMID- 23007176
TI  - Success story: Clontarf Foundation promotes education, life-skills and employment
      prospects through Australian Rules Football.

PMID- 23007178
TI  - Review of exercise studies in breast cancer survivors: attention to principles of
      exercise training.
AB  - OBJECTIVES: Research supports the use of exercise to improve quality of life and
      reduce the side effects of breast cancer treatment, such as fatigue and decreased
      aerobic capacity. Previously published reviews have focused on reporting the
      outcomes of exercise interventions, but have not critically examined the exercise
      prescriptions. The purpose of this review is to evaluate the application of the
      principles of exercise training in the exercise prescriptions reported in
      intervention studies for breast cancer survivors. METHODS: Databases were
      searched for randomised controlled trials of exercise in women diagnosed with
      breast cancer. Data were extracted to evaluate the application of the principles
      of exercise training, the reporting of the components of the exercise
      prescription and the reporting of adherence to the exercise prescription.
      RESULTS: Of the 29 papers included, none applied all principles of exercise
      training. Specificity was applied by 64%, progression by 41%, overload by 31%,
      initial values by 62% and diminishing returns and reversibility by 7% of trials.
      No study reported all components of the exercise prescription. CONCLUSION: The
      application of the principles of exercise training varied greatly, and reporting
      of the exercise prescribed and completed was incomplete. When principles of
      exercise training are applied to the development of exercise protocols, there is
      greater confidence that non-significant findings reflect lack of efficacy of
      exercise rather than deficiencies in the prescription. Incomplete reporting of
      the exercise prescription and adherence to the prescription limits the
      reproducibility of the intervention, and the ability to determine the dose of
      exercise received by participants.

PMID- 23007179
TI  - Television viewing time and reduced life expectancy: a life table analysis.
AB  - BACKGROUND: Prolonged television (TV) viewing time is unfavourably associated
      with mortality outcomes, particularly for cardiovascular disease, but the impact
      on life expectancy has not been quantified. The authors estimate the extent to
      which TV viewing time reduces life expectancy in Australia, 2008. METHODS: The
      authors constructed a life table model that incorporates a previously reported
      mortality risk associated with TV time. Data were from the Australian Bureau of
      Statistics and the Australian Diabetes, Obesity and Lifestyle Study, a national
      population-based observational survey that started in 1999-2000. The authors
      modelled impacts of changes in population average TV viewing time on life
      expectancy at birth. RESULTS: The amount of TV viewed in Australia in 2008
      reduced life expectancy at birth by 1.8 years (95% uncertainty interval (UI): 8.4
      days to 3.7 years) for men and 1.5 years (95% UI: 6.8 days to 3.1 years) for
      women. Compared with persons who watch no TV, those who spend a lifetime average
      of 6 h/day watching TV can expect to live 4.8 years (95% UI: 11 days to 10.4
      years) less. On average, every single hour of TV viewed after the age of 25
      reduces the viewer's life expectancy by 21.8 (95% UI: 0.3-44.7) min. This study
      is limited by the low precision with which the relationship between TV viewing
      time and mortality is currently known. CONCLUSIONS: TV viewing time may be
      associated with a loss of life that is comparable to other major chronic disease
      risk factors such as physical inactivity and obesity.

PMID- 23007181
TI  - Focus on neural control of feeding.

PMID- 23007182
TI  - To sleep: perchance to learn.

PMID- 23007183
TI  - Arc illuminates Alzheimer's pathophysiology.

PMID- 23007184
TI  - Knockout punch: cardiolipin oxidation in trauma.

PMID- 23007185
TI  - Sleep tight, wake up bright.

PMID- 23007186
TI  - Changing behavior with epigenetics.

PMID- 23007187
TI  - The drive to eat: comparisons and distinctions between mechanisms of food reward
      and drug addiction.
AB  - The growing rates of obesity have prompted comparisons between the uncontrolled
      intake of food and drugs; however, an evaluation of the equivalence of food- and
      drug-related behaviors requires a thorough understanding of the underlying neural
      circuits driving each behavior. Although it has been attractive to borrow
      neurobiological concepts from addiction to explore compulsive food seeking, a
      more integrated model is needed to understand how food and drugs differ in their
      ability to drive behavior. In this Review, we will examine the commonalities and
      differences in the systems-level and behavioral responses to food and to drugs of
      abuse, with the goal of identifying areas of research that would address gaps in
      our understanding and ultimately identify new treatments for obesity or drug
      addiction.

PMID- 23007188
TI  - Synaptic plasticity in neuronal circuits regulating energy balance.
AB  - Maintaining energy balance is of paramount importance for metabolic health and
      survival. It is achieved through the coordinated regulation of neuronal circuits
      that control a wide range of physiological processes affecting energy intake and
      expenditure, such as feeding, metabolic rate, locomotor activity, arousal, growth
      and reproduction. Neuronal populations distributed throughout the CNS but highly
      enriched in the mediobasal hypothalamus, sense hormonal, nutrient and neuronal
      signals of systemic energy status and relay this information to secondary neurons
      that integrate the information and regulate distinct physiological parameters in
      a manner that promotes energy homeostasis. To achieve this, it is critical that
      neuronal circuits provide information about short-term changes in nutrient
      availability in the larger context of long-term energy status. For example, the
      same signals lead to different cellular and physiological responses if delivered
      under fasted versus fed conditions. Thus, there is a clear need to have
      mechanisms that rapidly and reversibly adjust responsiveness of hypothalamic
      circuits to acute changes in nutrient availability.

PMID- 23007191
TI  - Quantum dot photosensitizers. Interactions with transition metal centers.
AB  - Semiconductor quantum dots (QDs) are attractive for potential use as
      photosensitizers for a variety of applications. These nanomaterials have very
      high absorption cross-sections and often display strong photoluminescence (PL).
      Furthermore, QD absorption and emission spectra can be tuned simply by varying
      their size, and QD surfaces can be modified to access multiple sites for
      attaching potential acceptors as well as other functionalities. Here we provide
      an overview of recent studies concerned with the photosensitization of transition
      metal centers and other acceptors. Particular focus is directed towards potential
      therapeutic applications and to our own interest in the delivery of small
      molecule bioregulators to physiological targets. Studies that have addressed
      factors that control likely energy and charge transfer processes between QD
      donors and acceptor molecules are also discussed. Understanding the mechanisms of
      these photosensitization processes can provide design guidelines for successful
      applications.

PMID- 23007189
TI  - Unraveling the brain regulation of appetite: lessons from genetics.
AB  - Over the past 20 years, genetic studies have illuminated critical pathways in the
      hypothalamus and brainstem mediating energy homeostasis, such as the
      melanocortin, leptin, 5-hydroxytryptamine and brain-derived neurotrophic factor
      signaling axes. The identification of these pathways necessary for appropriate
      appetitive responses to energy state has yielded insight into normal homeostatic
      processes. Although monogenic alterations in each of these axes result in severe
      obesity, such cases remain rare. The major burden of disease is carried by those
      with common obesity, which has so far resisted yielding meaningful biological
      insights. Recent progress into the etiology of common obesity has been made with
      genome-wide association studies. Such studies now reveal more than 32 different
      candidate obesity genes, most of which are highly expressed or known to act in
      the CNS, emphasizing, as in rare monogenic forms of obesity, the role of the
      brain in predisposition to obesity.

PMID- 23007190
TI  - From neuroanatomy to behavior: central integration of peripheral signals
      regulating feeding behavior.
AB  - Over the past two centuries, prevalent models of energy and glucose homeostasis
      have emerged from careful anatomical descriptions in tandem with an understanding
      of cellular physiology. More recent technological advances have culminated in the
      identification of peripheral and central factors that influence neural circuits
      regulating metabolism. This Review highlights contributions to our understanding
      of peripheral and central factors regulating food intake and energy expenditure.

PMID- 23007192
TI  - Structure relationship of cationic lipids on gene transfection mediated by
      cationic liposomes.
AB  - The aim of this study was to investigate the transfection efficiency of cationic
      liposomes formulated with phosphatidylcholine (PC) and novel synthesized
      diethanolamine-based cationic lipids at a molar ratio of 5:1 in comparison with
      LipofectamineTM 2000. Factors affecting transfection efficiency and cell
      viability, including the chemical structure of the cationic lipids, such as
      different amine head group (diamine and polyamine; and non-spermine and spermine)
      and acyl chain lengths (C14, C16, and C18) and the weight ratio of liposomes to
      DNA were evaluated on a human cervical carcinoma cell line (HeLa cells) using the
      pDNA encoding green fluorescent protein (pEGFP-C2). Characterizations of these
      lipoplexes in terms of size and charge measurement and agarose gel
      electrophoresis were performed. The results from this study revealed that almost
      no transfection was observed in the liposome formulations composed of cationic
      lipids with a non-spermine head group. In addition, the transfection efficiency
      of these cationic liposomes was in the following order: spermine-C14 > spermine
      C16 > spermine-C18. The highest transfection efficiency was observed in the
      formulation of spermine-C14 liposomes at a weight ratio of 25; furthermore, this
      formulation was safe for use in vitro. In conclusion, cationic liposomes
      containing spermine head groups demonstrated promising potential as gene
      carriers.

PMID- 23007193
TI  - Valproate as a treatment for dopamine dysregulation syndrome (DDS) in Parkinson's
      disease.
AB  - It has been previously well established that the use of dopaminergic agents in
      Parkinson's disease may contribute to behavioral disturbances such as dopamine
      dysregulation syndrome (DDS), impulse control disorders (ICD), and punding. ICD
      and punding have been most commonly addressed by reducing dose or by
      discontinuing the use of a dopamine agonist. Treatment of DDS has proven more
      challenging, and to date there has been no standard approach. In this paper, we
      review a series of four patients who met criteria for DDS, who were all
      refractory to medication adjustments. The DDS symptoms responded by the addition
      of valproic acid in all cases.

PMID- 23007194
TI  - Logopenic syndrome in posterior cortical atrophy.
AB  - Few language disorders have been reported in posterior cortical atrophy (PCA).
      Furthermore, no study has focused on screening for them and described these
      language deficits. The goal of this work was to describe linguistic examination
      of PCA patients and the impact of language disorders on neuropsychological
      performances compared to patients with other neurodegenerative syndromes and
      control groups. Linguistic examination of 9 PCA patients was carried out. The
      neuropsychological performance of the PCA group (16 patients) in the RAPID
      battery tests was compared with performances of patients with a logopenic variant
      of primary progressive aphasia (LPPA), patients with Alzheimer's disease and
      patients with amnestic mild cognitive impairment, as well as the control group. A
      "logopenic syndrome" with anomia, fluency impairment, and length-dependent
      deficit was found in 8/9 PCA patients. A comparison with other neurodegenerative
      syndromes showed that not only visual disorders but also language and verbal
      short-term memory disorders, such as those found in LPPA, can explain
      neuropsychological performances. A "logopenic syndrome" is frequently found in
      PCA and may be associated with poor performance on other verbally mediated
      neuropsychological tasks (e.g., verbal memory). Specific logopedic rehabilitation
      should be offered to these patients.

PMID- 23007196
TI  - Electrodeposition of catalytic and magnetic gold nanoparticles on dendrimer
      carbon nanotube layer-by-layer films.
AB  - Magnetic and catalytic gold nanoparticles were electrodeposited through potential
      pulse on dendrimer-carbon nanotube layer-by-layer (LbL) films. A plasmon
      absorption band at about 550 nm revealed the presence of nanoscale gold in the
      film. The location of the Au nanoparticles in the film was clearly observed by
      selecting the magnetic force microscopy mode. To our knowledge, this is the first
      report on the electrochemical synthesis of magnetic Au nanoparticles. In addition
      to the magnetic properties, the Au nanoparticles also exhibited high catalytic
      activity towards ethanol and glycerol oxidation in alkaline medium.

PMID- 23007195
TI  - Hirayama disease is a pure spinal motor neuron disorder--a combined DTI and
      transcranial magnetic stimulation study.
AB  - Hirayama disease (HirD) is a juvenile spinal muscular atrophy predominantly
      affecting young men with an initially progressive course followed by a stable
      plateau within several years. It is a matter of debate whether HirD is a
      widespread motor neuron or more focal cervical cord disease. Whether the
      supraspinal pathways of the corticospinal tract (CST) are also affected has not
      been studied systematically. We analyzed CST integrity in seven HirD patients and
      11 controls of similar age and gender using diffusion tensor imaging at a 1.5-T
      scanner and central motor conduction time (CMCT) using transcranial magnetic
      stimulation. The apparent diffusion coefficient, fractional anisotropy, and axial
      and radial diffusivity coefficients were determined bilaterally at four
      representative CST levels and along the whole CST using a probabilistic fiber
      tracking approach. There were no differences between the initially affected and
      the contralateral side in HirD patients and no difference between HirD patients
      and controls for both the ROI-based and the whole CST analyses. Radial
      diffusivity of the CST was positively correlated with years of disease
      progression in HirD patients. CMCT was normal in HirD patients. Combined
      anatomical and functional measurements established normal integrity of the
      supraspinal CST in HirD patients lending support to the notion that HirD is a
      pure spinal motor neuron disorder.

PMID- 23007197
TI  - High-throughput optical injection of mammalian cells using a Bessel light beam.
AB  - Femtosecond photoporation is an optical method for the injection of membrane
      impermeable substances into cells. Typically this is a low-throughput method
      where each cell is individually targeted. Here, we present a novel microfluidic
      platform with passive optical injection improving previously reported throughputs
      by one order of magnitude. In this new geometry, two-dimensional hydrodynamic
      focusing is achieved using a three-dimensional nozzle which confines mammalian
      cells to the central region of the microfluidic channel. A reusable quartz chip
      is designed so that a propagation invariant, 'non-diffracting' Bessel beam can be
      directed along the centre of the channel, parallel to but counter-propagating
      with the flow of cells in contrast to previous orthogonal geometries. This allows
      for higher flow speeds to be used whilst maintaining the necessary dwell time for
      cells in the core of the Bessel beam. Using this method, we have achieved viable
      injection of HL60 cells with propidium iodide with an efficiency of 20.4 +/- 4.2%
      and CHO-K1 cells (31.0 +/- 9.5%) at a rate of up to 10 cells s(-1).

PMID- 23007198
TI  - Allogeneic haematopoietic stem cell transplantation in a patient with cutaneous
      gamma/delta-T-cell lymphoma.

PMID- 23007199
TI  - Improved chemical shift prediction by Rosetta conformational sampling.
AB  - Chemical shift frequencies represent a time-average of all the conformational
      states populated by a protein. Thus, chemical shift prediction programs based on
      sequence and database analysis yield higher accuracy for rigid rather than
      flexible protein segments. Here we show that the prediction accuracy can be
      significantly improved by averaging over an ensemble of structures, predicted
      solely from amino acid sequence with the Rosetta program. This approach to
      chemical shift and structure prediction has the potential to be useful for
      guiding resonance assignments, especially in solid-state NMR structural studies
      of membrane proteins in proteoliposomes.

PMID- 23007201
TI  - Alkaloid concentration of the invasive plant species Ulex europaeus in relation
      to geographic origin and herbivory.
AB  - In the study of plant defense evolution, invasive plant species can be very
      insightful because they are often introduced without their enemies, and traits
      linked to defense can be released from selective pressures and evolve. Further,
      studying plant defense evolution in invasive species is important for biological
      control and use of these species. In this study, we investigated the evolution of
      the defensive chemicals quinolizidine alkaloids (QAs) in the invasive species
      gorse, Ulex europaeus. Using a common garden experiment, our goals were to
      characterize the role of QAs relative to specialist enemies of gorse and to
      investigate if QA concentration evolved in invaded regions, where gorse was
      introduced without these enemies. Our results showed that pod infestation rate by
      the seed predator Exapion ulicis and infestation by the rust pathogen Uromyces
      genistae-tinctoriae were negatively correlated to concentration of the QA
      lupanine. Quinolizidine alkaloid concentration was very variable between
      individuals, both within and among populations, but it was not different between
      native and invaded regions, suggesting that no evolution of decreased resistance
      occurred after gorse lost its enemies. Our study also suggests that QA
      concentrations are traits integrated into seed predation avoidance strategies of
      gorse, with plants that mass-fruit in spring but do not escape pod infestation in
      time being richer in QAs.

PMID- 23007202
TI  - Carboxylated polymers functionalized by cyclodextrins for the stabilization of
      highly efficient rhodium(0) nanoparticles in aqueous phase catalytic
      hydrogenation.
AB  - Rhodium(0) nanoparticles stabilized by a polymer containing carboxylate and beta
      cyclodextrin moieties have high stability and catalytic activity for aqueous
      hydrogenation reactions of olefins and aromatic substrates. This catalytic system
      can be recycled and reused without loss of activity. These high catalytic
      performances can be attributed to conjugated electrostatic interactions
      (carboxylate groups) and steric interactions (polymer structure and beta
      cyclodextrin moiety).

PMID- 23007203
TI  - Pitch chroma discrimination, generalization, and transfer tests of octave
      equivalence in humans.
AB  - Octave equivalence occurs when notes separated by an octave (a doubling in
      frequency) are judged as being perceptually similar. Considerable evidence points
      to the importance of the octave in music and speech. Yet, experimental
      demonstration of octave equivalence has been problematic. Using go/no-go operant
      discrimination and generalization, we studied octave equivalence in humans. In
      Experiment 1, we found that a procedure that failed to show octave equivalence in
      European starlings also failed in humans. In Experiment 2, we modified the
      procedure to control for the effects of pitch height perception by training
      participants in Octave 4 and testing in Octave 5. We found that the pattern of
      responding developed by discrimination training in Octave 4 generalized to Octave
      5. We replicated and extended our findings in Experiment 3 by adding a transfer
      phase: Participants were trained with either the same or a reversed pattern of
      rewards in Octave 5. Participants transferred easily to the same pattern of
      reward in Octave 5 but struggled to learn the reversed pattern. We provided
      minimal instruction, presented no ordered sequences of notes, and used only sine
      wave tones, but participants nonetheless constructed pitch chroma information
      from randomly ordered sequences of notes. Training in music weakly hindered
      octave generalization but moderately facilitated both positive and negative
      transfer.

PMID- 23007204
TI  - Effects of changes in size, speed, and distance on the perception of curved 3-D
      trajectories.
AB  - Previous research on the perception of 3-D object motion has considered time to
      collision, time to passage, collision detection, and judgments of speed and
      direction of motion but has not directly studied the perception of the overall
      shape of the motion path. We examined the perception of the magnitude of
      curvature and sign of curvature of the motion path for objects moving at eye
      level in a horizontal plane parallel to the line of sight. We considered two
      sources of information for the perception of motion trajectories: changes in
      angular size and changes in angular speed. Three experiments examined judgments
      of relative curvature for objects moving at different distances. At the closest
      distance studied, accuracy was high with size information alone but near chance
      with speed information alone. At the greatest distance, accuracy with size
      information alone decreased sharply, but accuracy for displays with both size and
      speed information remained high. We found similar results in two experiments with
      judgments of sign of curvature. Accuracy was higher for displays with both size
      and speed information than with size information alone, even when the speed
      information was based on parallel projections and was not informative about sign
      of curvature. For both magnitude of curvature and sign of curvature judgments,
      information indicating that the trajectory was curved increased accuracy, even
      when this information was not directly relevant to the required judgment.

PMID- 23007205
TI  - The effects of marker-related temporal cues on auditory gap-duration
      discrimination.
AB  - In three experiments, we examined the ability of listeners to discriminate the
      duration of temporal gaps (silent intervals) and the influence of other temporal
      stimulus properties on their performance. In the first experiment, gap-duration
      discrimination thresholds were measured either in continuous noise or with noise
      markers with durations of 3 and 300 ms. Thresholds measured with 300-ms markers
      differed from those measured in continuous noise or with 3-ms markers. In the
      second experiment, stimuli consisting of a gap between two discrete markers were
      generated such that the gap duration, the onset-to-onset duration between
      markers, and the duration of the first marker were pseudorandomized across
      trials. Listeners' responses generally were consistent with the cue that was
      identified as the target cue from among the three cues in each block of trials,
      but the data suggested that the onset-to-onset cue was particularly salient in
      all conditions. Using a modified method-of-adjustment procedure in the third
      experiment, subjects were instructed to discriminate between the durations of
      gaps in discrete markers of different durations in two intervals, where the gap
      duration in one interval was adapted to measure the point of subjective equality.
      Without feedback, listeners tended to equate the onset-to-onset times of the
      markers rather than the gap durations. Overall, the results indicated that
      listeners' judgments of silent gaps between two discrete markers are strongly
      influenced by the onset-to-onset time, or rhythm, of the markers.

PMID- 23007206
TI  - Catching a glimpse of working memory: top-down capture as a tool for measuring
      the content of the mind.
AB  - This article outlines a methodology for probing working memory (WM) content in
      high-level cognitive tasks (e.g., decision making, problem solving, and memory
      retrieval) by capitalizing on attentional and oculomotor biases evidenced in top
      down capture paradigms. This method would be of great use, as it could measure
      the information resident in WM at any point in a task and, hence, track
      information use over time as tasks dynamically evolve. Above and beyond providing
      a measure of information occupancy in WM, such a method would benefit from
      sensitivity to the specific activation levels of individual items in WM. This
      article additionally forwards a novel fusion of standard free recall and visual
      search paradigms in an effort to assess the sensitivity of eye movements in top
      down capture, on which this new measurement technique relies, to item-specific
      memory activation (ISMA). The results demonstrate eye movement sensitivity to
      ISMA in some, but not all, cases.

PMID- 23007207
TI  - Sexually transmitted infections and diseases: old and new challenges - part I -
      Introduction.

PMID- 23007208
TI  - History of sexually transmitted infections (STI).
AB  - Sexually transmitted diseases (STD) are as old as mankind and epidemics are
      mentioned already in the Old Testament. However, the perception of the conditions
      has changed over the centuries. In ancient times they were taken for an
      individual punishment for a blasphemic conduct of life or as a consequence of low
      sanitation and hygiene. In the medieval ages, the relation to sexual activities
      was recognized, but the diversity of clinical symptoms was seen as variations of
      one disease, depending on the stage of the disease and the general health
      condition of the diseased person. In the late 15th and 16th century a presumably
      "new plague" had been imported to Europe and was rapidly spread by soldiers.
      Misinterpretations of wrong experiments on the suspected identity of syphilis and
      gonorrhoea led to nosologic misconceptions in the 17th and early 19th century.
      The late 19th and beginning of 20st century due to the many achievements in
      microbiology and chemistry finally took the frightening threat from the STDs,
      which have terrorized millions of "normal" and "famous" people of all social
      classes over centuries and has been linked to many scandals. Moreover, the
      perception of STDs has turned from a "personal stroke of fate" into a
      collectively important issue of public health.

PMID- 23007209
TI  - Social and behavioral determinants as risk of sexually transmitted diseases.
      Report by a sample from the Sexually Transmitted Disease Unit in Florence, Italy.
AB  - AIM: Sexually transmitted infections (STIs) are increasing worldwide, mostly due
      to changing sexual behavior s (larger numbers of sexual partners, concurrent
      relationships, increasing proportion of adolescents engaging in sexual
      intercourse at young age, and inconsistent condom use with new partners). In
      Italy, few data are available about STI spread, since most infections are not
      subjected to mandatory notification. METHODS: In this article, the occurrence of
      STIs in a random sample attending a STI Unit in Florence, Italy, is reported.
      Results were obtained through the administration of an anonymous questionnaire
      that patients could complete spontaneously in the waiting room while waiting for
      the visit. Self-reported questions allowed to collect information about socio
      demographic and clinical data, sexual behavior and perception of risk. RESULTS:
      Overall, 469 patients (321 males, 148 females) participated in the study. Age
      ranged from 16 to 70 years. Male patients who referred to engage sexual
      intercourse with men (MSM) were 133; females who had sex with women (FSF) were 5,
      while 24 patients declared to have sex with both males and females (bisexual);
      59.7% (N.=280) of participants reported they had a stable relationship, but 20%
      of these reported they had had sex with more than five partners during the last
      12 months. The use of condoms is declared to be very infrequent, especially in
      the two extreme age ranges. Fifty percent of patients had been diagnosed an STI
      in their life, particularly syphilis (39.3%), genital warts (64.6%) and
      chlamydial infections (42.9%). Among those subjects who had contracted an STI
      (including non-curable viral infections, i.e., HIV and herpes genitalis) 32.4%
      referred they never used condoms. CONCLUSION: The authors discuss their results
      compared to the existing literature, and focus on identification of risk factors
      associated with self-reported STIs. Although conducted on a small population,
      this study provides a basis for targeting prevention and control strategies on
      our high-risk patients.

PMID- 23007210
TI  - Prostitution, sexual behavior and STDs.
AB  - Prostitution involves the exchange of sexual services for economic compensation.
      As sexual behaviour is an important determinant in transmitting HIV and sexually
      transmitted diseases (STDs), sex workers (SWs), transgenders and clients are
      often labeled as a "high risk group" in the context of HIV and STDs. It has been
      documented that female sex workers in particular have an increased prevalence of
      untreated STDs and have been hypothesized to affect the health and HIV incidence
      of the general population. People involved in prostitution are a cause for
      concern from both public health and economic perspectives. However, little is
      known about why they remain in this type of activity given the risks prostitution
      presents, and even less is known about how to intervene and interrupt the complex
      cycle of prostitution. The aim of this paper is to provide a clinical and
      epidemiological analysis of the relationship between prostitution, sexual
      behavior and outbreaks of STDs; to assess the role that migrants, transgenders
      and clients of SWs have in prostitution and in the outbreaks of STDs. In
      addition, we also want to highlight how new sexual networks, like the Internet,
      have become an increasingly important vehicle to sharing information about
      prostitution, sexual behavior and STDs. Finally we present what may be the
      prevention strategies and the goals in order to stem the spread of STDs among
      these hard-to-access groups.

PMID- 23007211
TI  - Legal aspects of sexually transmitted diseases: abuse, partner notification and
      prosecution.
AB  - Sexually transmitted diseases (STDs), with special emphasis to HIV infection,
      involve legal and ethical issues regarding informed consent to submit to a
      diagnostic, observance of professional secrecy in regard to partner(s) and
      community; legal troubles of particular difficulties are related to STD involving
      minors; lastly, physicians must be able to recognize the state of so called
      medical necessity. Knowledge and awareness of these related obligations are
      crucial to STD in medical practice; it is also important to allow for proper
      protection of victims of suspected sexual abuse under observation of healthcare.
      With regard to this aspect should be emphasized that violence against women and
      minors is a worldwide problem that has not yet been sufficiently acknowledged.
      Italian legislation (Law n. 96/1996) against rapes finally gave significant
      relevance to sex crimes. When sexual abusers have to be evaluated some obstacles
      may arise for lack of appropriate interdisciplinary approach, with insurance of
      the collection of biological samples, also related to STD diagnosis and alerts of
      legal authorities. Personal preconceptions may interfere with investigation if
      the biological evidences in children are few. In this regard, rules of document
      "Carta di Noto" drafted in 1996 and reviewed in July 2002 include some specific
      indications aiming to grant the reliability of the results of technical
      investigations and authenticity of the statements of the alleged victims.

PMID- 23007212
TI  - Oral manifestations of sexually transmitted infections.
AB  - It's difficult to establish the real risks associated with all forms of oral sex
      and the contribution they may make to the overall number of newly diagnosed cases
      of sexually transmitted infections (STIs). This article reviews the literature on
      the role of oral sex in the transmission of STIs and the corresponding clinical
      presentations. Oral sex is becoming a common sexual practice between both
      heterosexual and homosexual couples because it is seen as a safer alternative to
      penetrative sex and a safer challenge to an individual's hidden identity. Because
      of the frequency with which oral sex occurs, and the rarity with which it is
      protected, oral sex may raise justified alarming attention to underestimated
      orally acquired STIs.

PMID- 23007213
TI  - Sexually transmitted diseases syndromic approach: urethral discharge.
AB  - Urethral discharge (UD) in men is one of the most identifiable sexually
      transmitted infections (STI)-associated syndromes. UD performs very well, giving
      the possibility of an accurate diagnosis, a treatment at first encounter, a rapid
      cure with effective drugs, a modification of the risk behavior. Furthermore the
      patient is informed about the infectious nature of STDs, the transmission through
      sexual intercourse, the increased risks of infertility and other complications
      and, finally, the importance of completing treatment, even after improvement.
      Applying the syndromic approach to UD has resulted in effective case management
      of urethritis, as shown in different studies. Thus, there are numerous reasons
      why treatment of gonorrhea should include a regimen with complete in vivo
      activity against both N. gonorrhoeae and C. trachomatis.

PMID- 23007214
TI  - Sexually transmitted diseases syndromic approach: proctitis.
AB  - Proctitis is a common problem and is most frequently associated with inflammatory
      bowel diseases (IBD). However, in the last ten years the incidence of infectious
      proctitis appears to be rising, especially in men who have sex with men. This may
      be due to the rise of people participating in receptive anal sex as well as the
      increase in sexually transmitted infections, such as those from Chlamydia
      trachomatis, Neisseria gonorrhoeae, Herpes simplex virus and Treponema pallidum.
      Recent outbreaks of lymphogranuloma venereum among homosexual men throughout
      Europe highlight the need to consider sexually transmitted infections in the
      differential diagnosis of proctitis. Symptoms of infectious proctitis can include
      rectal blood and mucous discharge, anorectal pain, aphtous ulcers and, sometimes,
      generalized lymphadenopathy and fever. A careful history and physical examination
      are crucial in establishing a diagnosis, eventually supported by endoscopy,
      histology, serology, culture and PCR. Treatment with antibiotics or antivirals is
      usually initiated, either empirically or after establishing a diagnosis.
      Coinfections, HIV testing, and treatment of sexual partners should always be
      considered.

PMID- 23007215
TI  - Preoperative advantages of HF sonography of pilonidal sinus.
AB  - AIM AND METHODS: Pilonidal sinus is a not infrequent disease, probably due to a
      disontogenetic origin. Histologically, there is a pseudocystic formation in the
      subcutaneous adipose tissue, containing some hair bulbs. It usually presents a
      recurring inflammatory course. The pathologic formation does not normally have
      thick wall, being made up of thin epidermal epithelium, without internal
      vascularisation and with frequent subcutaneous fistulae. Even though the clinical
      diagnosis is rather easy, surgery may prove, on the contrary, a demanding task,
      with a high incidence of recurrence and complications. An adequate knowledge of
      the condition and its development, with a precise definition of the margins of
      the lesions, may simplify the surgery, reducing the chance of recurrence or
      complications. The use of echography in the diagnosis of this disease, in our
      cohort of 72 patients, has always provided valuable information. In particular,
      13 and 18 MHz linear probes and 20 MHz mechanical array have been used, and the
      latter in particular for the evaluation of fistolous cavities/passageways under
      the skin. Results. In all our cases, echography has demonstrated pseudocystic
      formations, without real walls, with fairly high levels of internal echoes,
      compared to the hair follicles, or, more rarely, true macrocalcifications with
      one or more cavities/passageways near the skin, without internal vascularisation,
      according to the histological findings. Echographic data are rapidly obtained,
      and can prove useful for surgeons for a a better management of patients.
      Conclusion. We consider diagnostic echography, using high frequency probes,
      useful for the anatomical definition of this disease, as well as to enable better
      surgical management.

PMID- 23007216
TI  - Melasma.
AB  - Melasma is a common disorder of hyperpigmentation that is present most commonly
      in reproductive age women with brown or black skin colors. The lesions of melasma
      are characteristically distributed in a symmetric manner on the sun-exposed areas
      of the face and neck. The precise pathogenesis of the disorder is unknown, but a
      number of etiologic agents have been implicated as its cause. These include
      ultraviolet radiation, hormonal alterations such as those evident during
      pregnancy, thyroid dysfunction, and phototoxic and anti-seizure drugs. The
      pathophysiology of melasma is believed to involve excess production of melanin or
      an increase in the number of melanocytes in the skin. This is confirmed by
      histological analysis of melasma, which shows an increased number of melanocytes
      along with an enhanced capability of these cells to produce melanin. Lack of an
      understanding of the precise pathogenesis of the condition has led to a large
      number of treatments for melasma. These therapies include hypopigmenting agents,
      chemical peels, lasers, and dermabrasion. Further investigations into this
      disorder may lead to more specific and effective treatments in the future.

PMID- 23007217
TI  - Papalomoyo (or papalomayo): what is it?

PMID- 23007218
TI  - The "shark" island flap in the reconstruction of nasal ala and perialar defects.

PMID- 23007219
TI  - Medical students and the Affordable Care Act: uninformed and undecided.

PMID- 23007220
TI  - Improved survival rates possible after prolonged resuscitation attempts.

PMID- 23007222
TI  - Lumbar spinal stenosis minimally invasive treatment with bilateral transpedicular
      facet augmentation system.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of a new
      pedicle screw-based posterior dynamic stabilization device PDS Percudyn SystemTM
      Anchor and Stabilizer (Interventional Spine Inc., Irvine, CA) as alternative
      minimally invasive treatment for patients with lumbar spine stenosis. METHODS:
      Twenty-four consecutive patients (8 women, 16 men; mean age 61.8 yr) with lumbar
      spinal stenosis underwent implantation of the minimally invasive pedicle screw
      based device for posterior dynamic stabilization. Inclusion criteria were lumbar
      stenosis without signs of instability, resistant to conservative treatment, and
      eligible to traditional surgical posterior decompression. RESULTS: Twenty
      patients (83 %) progressively improved during the 1-year follow-up. Four (17 %)
      patients did not show any improvement and opted for surgical posterior
      decompression. For both responder and nonresponder patients, no device-related
      complications were reported. CONCLUSIONS: Minimally invasive PDS Percudyn
      SystemTM has effectively improved the clinical setting of 83 % of highly selected
      patients treated, delaying the need for traditional surgical therapy.

PMID- 23007221
TI  - Mechanisms of cardiac dysfunction in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and
      mortality, largely as a result of myocardial anomalies. Numerous mechanisms cause
      OSA-related myocardial damage. The majority are initiated as a result of OSA
      induced, chronic, intermittent hypoxia. The most-important mechanisms that lead
      to myocardial damage are increased sympathetic activity, endothelial dysfunction,
      systemic inflammation, oxidative stress, and metabolic anomalies. All these
      mechanisms promote the development of hypertension, which is common in patients
      with OSA. Hypertensive cardiomyopathy and coronary heart disease, as well as
      obesity-related, diabetic, and tachycardia-induced cardiomyopathies, are also
      associated with OSA. Left ventricular hypertrophy, myocardial fibrosis, atrial
      dilatation, and left ventricular systolic and diastolic dysfunction in patients
      with OSA explain the association of the disease with these clinical outcomes. The
      gold-standard treatment for OSA, nasal continuous positive airway pressure
      (CPAP), might improve cardiac symptoms and hemodynamic parameters in patients
      with the disease. However, large clinical trials are required to improve our
      understanding of the cardiac consequences of OSA, and determine the effect of
      treatment, particularly CPAP, on myocardial damage in symptomatic patients and
      primary prevention of cardiovascular disorders.

PMID- 23007223
TI  - Neointimal hyperplasia after silverhawk atherectomy versus percutaneous
      transluminal angioplasty (PTA) in femoropopliteal stent reobstructions: a
      controlled, randomized pilot trial.
AB  - BACKGROUND: Due to intimal hyperplasia instent reobstruction in the
      femoropopliteal arterial segment is still an unsolved problem. Different
      techniques have been discussed in case of reintervention to guarantee longlasting
      patency rate. METHODS: We conducted a randomized, controlled, pilot trial
      comparing Silverhawk atherectomy with percutaneous transluminal angioplasty (PTA)
      in patients with a first instent reobstruction in the femoropopliteal arterial
      segment, to evaluate intima media thickness (IMT) within the treated segment, as
      a parameter of recurrence of intimal hyperplasia. RESULTS: In a total 19 patients
      were included: 9 patients in the atherectomy device and 10 patients in the PTA
      arm. IMT within the treated segment was statistically significantly elevated in
      all patients treated with the Silverhawk device versus the patients treated with
      PTA. The obvious differentiation in elevation of IMT in nonfavor for patients
      treated with the Silverhawk device started at month 2 (max IMT SH 0.178 mm vs.
      IMT PTA 0.1 mm, p = 0.001) with a spike at month 5 (max IMT SH 0.206 mm vs. IMT
      PTA 0.145 mm, p = 0.003) and a decline once again at month 6 (max IMT SH 0.177 mm
      vs. IMT PTA 0.121 mm, p = 0.02). The values for mean IMT performed the same way.
      CONCLUSIONS: Although Silverhawk atherectomy provides good results at first
      sight, in the midterm follow-up of treatment of first instent restenosis it did
      not perform better than PTA as it showed elevated reoccurrence of intimal media
      hyperplasia.

PMID- 23007224
TI  - Radioembolization of the spleen: a revisited approach for the treatment of
      malignant lymphomatous splenomegaly.
AB  - Intraarterial administration of (90)Y microspheres to the spleen in patients with
      malignant lymphoma was mentioned once in the literature in 1973. This case study
      illustrates the potential indication of selective internal radiotherapy in a
      heavily pretreated patient with highly refractory disease with a marginal zone
      lymphoma in leukemic phase and symptomatic splenomegaly. We describe the clinical
      course of disease; the biological and clinical response to the treatment after
      radioembolization; and simulation and dosimetry by multimodal imaging via single
      photon emission computed tomography and computed tomography. The advantages of
      radioembolization for the management of lymphomatous splenomegaly are discussed. 

PMID- 23007225
TI  - Successful recanalization of acute superior mesenteric artery thromboembolic
      occlusion by a combination of intraarterial thrombolysis and mechanical
      thrombectomy with a carotid filter.
AB  - Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease,
      and acute intestinal ischemia develops from the sudden decrease in perfusion to
      the intestines. The key to saving the patient's life is early diagnosis, and
      prompt revascularization of the SMA can prevent intestinal infarction and
      decrease the risk of bowel segment necrosis. Computed tomographic angiography may
      be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an
      80-year-old man with a combination of intraarterial thrombolysis and mechanical
      thrombectomy with a carotid filter.

PMID- 23007226
TI  - The metabolic syndrome of fructose-fed rats: effects of long-chain
      polyunsaturated omega3 and omega6 fatty acids. VII. Oxidative stress.
AB  - In the present study, the plasma concentration, and liver, heart, kidney, soleus
      muscle and visceral adipose tissue content of thiobarbituric acid reactive
      substrates (TBARS), carbonyl radicals, hydroperoxides and nitric oxide were
      measured in control rats exposed for 8 weeks to a diet containing 64% (w/w)
      starch and 5% sunflower oil and in animals fed a diet containing 64% D-fructose
      and 5% sunflower oil or 3.4% sunflower oil mixed with 1.6% safflower or salmon
      oil. Coherent measurements of the plasma concentrations or tissue contents of
      these metabolites revealed increases in TBARS, carbonyl radical and hydroperoxide
      levels and a decrease in nitric oxide levels in the 5% sunflower oil-fed rats. In
      the fructose-fed rats, the partial substitution of sunflower oil by either
      safflower or salmon oil minimized the changes. These findings provide further
      evidence in support of the favorable effects of the dietary supply of long-chain
      polyunsaturated omega6 and omega3 fatty acids upon the metabolic disturbances
      prevailing in the fructose-induced metabolic syndrome.

PMID- 23007227
TI  - Direct and indirect effects of imidacloprid on fecundity and abundance of
      Eurytetranychus buxi (Acari: Tetranychidae) on boxwoods.
AB  - Populations of spider mites often reach high levels on urban plants. In many
      cases, insecticide applications targeting other herbivores trigger outbreaks of
      spider mites. Recently, elevated populations of spider mites on a diversity of
      plants in urban landscapes have been associated with applications of
      imidacloprid, a neonicotinoid insecticide. Imidacloprid has also been linked to
      increased fecundity in two species of spider mites. In this study, we evaluated
      the indirect (plant-mediated) and direct impact of imidacloprid on fecundity and
      longevity of Eurytetranychus buxi Garman (Acari: Tetranychidae), feeding on
      boxwoods, Buxus sempervirens L. Moreover, we compared the abundance of E. buxi on
      imidacloprid-treated and untreated boxwoods in the landscape and a greenhouse to
      determine if changes in the fecundity of mites exposed to imidacloprid were
      linked to outbreaks of E. buxi. We found that females consuming imidacloprid
      treated plants laid more eggs than females feeding on untreated boxwoods, while
      their longevity remained unchanged. Fecundity was not affected, however, when
      spider mites were directly sprayed with imidacloprid and consumed foliage of
      untreated boxwoods. Furthermore, populations of E. buxi were greater on boxwoods
      treated with imidacloprid in the landscape and greenhouse. On landscape boxwoods,
      elevated populations of E. buxi persisted into a second year. We also observed
      general lack of predators of spider mites on treated and untreated boxwoods in
      the field suggesting that imidacloprid's eruptive effect on E. buxi stems more
      from indirect changes in plant quality than from a loss of top-down regulation
      from E. buxi's natural enemies.

PMID- 23007228
TI  - Methods for rearing scutacarid mites (Acari, Heterostigmatina) and the influence
      of laboratory cultures on morphometric variables.
AB  - Mites of the soil inhabiting family Scutacaridae (Heterostigmatina) are
      distributed throughout the world, but only rarely found in high densities. Larvae
      and males are extremely difficult to detect and identify in soil samples.
      Laboratory cultures are necessary to describe these life stages, detect female
      dimorphism, or carry out other kinds of biological study. The present paper gives
      an historical overview of the methods applied for rearing scutacarids,
      demonstrating that thus far the use of glass tubes stuffed with soil is the most
      valuable method. Morphometric comparisons between field collected and laboratory
      reared specimens of two scutacarid species, Scutacarus acarorum Goeze and
      Heterodispus foveatus Jagersbacher-Baumann and Ebermann, revealed a clear
      influence of environmental conditions on the phenotype of laboratory-reared
      mites. Size correction minimized the environmentally induced variation and should
      therefore be mandatory for classification of species based on morphometric
      variables. Taxonomic assignment of laboratory reared scutacarids is possible, but
      must be done with extreme caution.

PMID- 23007229
TI  - Pattern of uveitis in an Egyptian population with multiple sclerosis: a hospital
      based study.
AB  - PURPOSE: To investigate the prevalence and pattern of uveitis in patients with
      multiple sclerosis (MS). PATIENTS AND METHODS: This is a cross-sectional,
      observational, descriptive clinical study of patients with MS who had complete
      ophthalmological examination. Data collected comprised demographics of the
      patients and complete ocular examination findings. Exclusion criteria were
      history of ocular surgery, trauma or diagnosis of any other ocular pathology.
      RESULTS: Seventy-five patients with a mean age of 32.64 years (ranging from 16 to
      50) diagnosed with MS of the relapsing-remitting type were included in this
      study. There were 34 males and 41 females, a ratio of 5:6. The mean duration of
      the MS disease was 5.6 years. Eight eyes of 7 patients with a mean age of 20
      years had intermediate uveitis, of which 5 were males. Out of the 7 patients, 5
      had exacerbated MS, and 2 were in remission; 4 had relative afferent pupillary
      defect. In the 8 eyes with uveitis, 6 had a best spectacle-corrected visual
      acuity (BSCVA) of 1, 1 had a BSCVA of 0.5 and 1 had a BSCVA of 0.25. CONCLUSION:
      Uveitis occurs in about 10% of patients with MS affecting younger males with
      exacerbated disease. Most inflammations of the uveitic MS patients were in the
      form of intermediate uveitis that was controlled with medication with no visual
      threatening complications.

PMID- 23007230
TI  - Paediatric acute generalized exanthematous pustulosis induced by paracetamol with
      high serum levels of interleukin-8 and -22: a case report.

PMID- 23007231
TI  - The charge transfer kinetics of the oxidation of silver and nickel nanoparticles
      via particle-electrode impact electrochemistry.
AB  - The electro-oxidation of silver and nickel nanoparticles in aqueous solution was
      studied via their collisions with a carbon electrode. The average charge passed
      per impact varies with electrode potential and was analysed to determine that
      AgNPs display an electrochemically fast ("reversible") one-electron oxidation,
      whilst the NiNPs exhibit slow ("irreversible") 2-electron kinetics. Kinetic
      parameters are reported.

PMID- 23007232
TI  - Summary of prognostic factors for choroidal neovascularization due to
      pathological myopia treated by intravitreal bevacizumab injection.
AB  - AIM: This systematic review assesses the prognostic factors for intravitreal
      bevacizumab injection (IVB) in the treatment of choroidal neovascularization
      (CNV) due to pathological myopia. METHODS: The literature searches were performed
      in Ovid Medline, EMBASE and CENTRAL. Relevant studies with prognostic data on
      best corrected vision acuity (BCVA) after intravitreal bevacizumab injection were
      included for review. Two reviewers participated in the data retrieval and
      independently assessed each included study. RESULTS: A total 252 articles were
      retrieved, including 16 studies containing the most updated and complete data on
      prognostic factors for neovascularization due to pathological myopia treated by
      intravitreal bevacizumab injection. A great number of quantitative, clinical, and
      treatment-related factors were determined to have a positive influence on vision
      outcome after intravitreal bevacizumab. CONCLUSION: A lower rate of development
      of chorioretinal atrophy, smaller pretreatment CNV size, and younger age were
      indentified as the most consistently significant prognostic factors affecting the
      efficacy of IVB in eyes of myopic CNV and were associated with improved BCVA. A
      worse BCVA after IVB in eyes with myopic CNV probably was associated with
      subfoveal CNV, lower baseline BCVA, longer duration of CNV, incomplete regression
      of CNV, subretinal hemorrhage, and previous PDT treatment. No apparent
      association were observed between the refraction error, axial length, lens status
      and change in BCVA after IVB. We indentified significant prognostic factors in
      this systematic review study that might allow for the selection of patients with
      myopic CNV which are most likely to benefit from IVB.

PMID- 23007233
TI  - Impact of simulator training on resident cataract surgery.
AB  - BACKGROUND: Virtual reality surgery simulation training improves resident
      performance as measured by the simulator itself and wet-lab performance. This
      study aims to determine whether virtual surgery simulator training improves
      actual resident cataract surgery performance. METHODS: The first 50
      phacoemulsification cases of 20 residents, at a single residency program (Henry
      Ford Hospital), were retrospectively compared as two groups: before (2007-8) and
      after (2009-10) introduction of the Eyesi virtual surgery simulator to the
      surgical training program. Primary outcomes were the incidence of posterior
      capsule tears and operation duration. All residents received traditional didactic
      and wet-lab training. Instructor surgeons were surveyed for their impression of
      the simulator's contribution to resident surgical training. RESULTS: The
      nonsimulator and simulator groups each comprised 500 cases with 40 and 35
      posterior capsule tears respectively. Capsular tear rates for the nonsimulator
      and simulator groups were 8.8 % and 10 % respectively for the first 25 cases, and
      7.2 % and 3.6 % (P = 0.11) respectively for cases 26 through 50 . The percentage
      of long cases (defined as >40 min) for cases 10 through 50 was 42.3 % and 32.4 %
      (P = 0.005) for the nonsimulator and simulator groups respectively. CONCLUSIONS:
      Virtual reality surgical simulator training mildly shortens the learning curve
      for the first 50 phacoemulsification cases. The less adept residents appear to
      benefit most.

PMID- 23007234
TI  - [Imaging in rheumatic diseases. Rheumatoid arthritis and differential
      diagnostics].
AB  - Differential diagnostics of arthritides is challenging even for experienced
      radiologists. Nevertheless, there are simple signs that can give important clues
      to make a diagnosis. Close cooperation with the attending clinicians is essential
      to get the most from imaging studies and to provide relevant information for
      patient management and therapy.

PMID- 23007235
TI  - Representations of interobject spatial relations in long-term memory.
AB  - A growing body of evidence has indicated that human spatial memory is organized
      in terms of a small number of reference directions and that interobject spatial
      relations are represented in terms of these directions (e.g., McNamara, 2003).
      The goal of the present experiments was to investigate whether the selection of
      reference directions also affects the fidelity with which interobject spatial
      relations are represented in memory. In two experiments, participants memorized a
      layout of nine objects and then performed judgments of relative direction (e.g.,
      "Imagine you are standing at the clock, facing the book. Point to the phone.") at
      a remote location. Imagined heading (e.g., at the clock, facing the book) and
      allocentric target direction (e.g., the direction from clock to phone in the
      allocentric frame of reference used to define imagined heading) were manipulated
      independently. The results of both experiments showed that the same directions
      that were benefited in imagined headings were also benefited in allocentric
      target directions. These findings indicate that interobject spatial relations are
      preferentially represented when they coincide with a reference direction.

PMID- 23007236
TI  - Kinetics of IgM and IgA antibody response to 23-valent pneumococcal
      polysaccharide vaccination in healthy subjects.
AB  - PURPOSE: A poor antibody response of IgM and IgA antibodies upon vaccination with
      pneumococcal polysaccharides (PnPS) is discussed as independent risk factors for
      bronchiectasis in patients with antibody deficiency syndrome (ADS) receiving
      immunoglobulin replacement therapy. However, the kinetics of the specific IgM and
      IgA response to vaccination with multivalent pneumococcal polysaccharides
      requires a more detailed knowledge. In this study we aimed i) to develop a
      standardised multivalent PnPS-IgM and IgA-ELISA, and ii) to compare the
      sensitivity of the multivalent to the serotype specific antibody response, and
      iii) to determine the kinetics of the anti-PnPS IgM and IgA antibodies in healthy
      subjects. METHODS: We immunised n=20 healthy adults with a 23-valent PnPS vaccine
      (Pneumovax(r)). The kinetics of the 23-valent antibody response was assessed for
      1 year with newly developed ELISAs for IgM and IgA isotypes, along with serotype
      specific responses. RESULTS: The IgA and IgM antibody response peaked at 2 and 3
      weeks, respectively. IgM antibody levels remained at a plateau (above 80 % of
      peak response) for 3 months. After one year, specific antibody levels were still
      at about 30 % of the peak response. The 23-valent antibody response yielded
      significantly higher responder rates than assessment of single serotypes.
      CONCLUSION: Testing the IgM and IgA immune response to polysaccharide vaccination
      with a multivalent PnPS ELISA may be a feasible tool for assessment of the immune
      function in patient groups who receive IgG replacement therapy.

PMID- 23007237
TI  - An inhibitory role for Sema4A in antigen-specific allergic asthma.
AB  - PURPOSE: The class IV semaphorin Sema4A is critical for efficient Th1
      differentiation and Sema4a (-/-) mice exhibit impaired Th1 immune responses.
      However, the role of Sema4A in Th2 cell-mediated allergic diseases has not been
      fully studied. The aim of this study was to clarify the regulatory role possessed
      by Sema4A in mouse models of allergic diseases, particularly allergic asthma.
      METHODS: Sema4a (-/-) mice on a BALB/c background were examined for the
      development of allergic diseases. To induce experimental asthma, mice were
      sensitized with ovalbumin (OVA) followed by intranasal challenges with OVA. After
      challenge, airway hyperreactivity (AHR) and airway inflammation were evaluated.
      The role of Sema4A in asthma was examined using Sema4a (-/-) mice and Sema4A-Fc
      fusion proteins. The direct effects of Sema4A-Fc on antigen-specific effector
      CD4(+) T cells were also examined. RESULTS: A fraction of Sema4a (-/-) BALB/c
      mice spontaneously developed skin lesions that resembled atopic dermatitis (AD)
      in humans. Furthermore, AHR, airway inflammation, and Th2-type immune responses
      were enhanced in Sema4a (-/-) mice compared to wild type (WT) mice when immunized
      and challenged with OVA. In vivo systemic administration of Sema4A-Fc during the
      challenge period ameliorated AHR and lung inflammation and reduced the production
      of Th2-type cytokines in WT mice. The inhibitory effects of Sema4A on airway
      inflammation were also observed in mice deficient in Tim-2, a Sema4A receptor.
      Finally, we showed that Sema4A-Fc directly inhibited IL-4-producing OVA-specific
      CD4(+) T cells. CONCLUSION: These results demonstrate that Sema4A plays an
      inhibitory role in Th2-type allergic diseases, such as allergic asthma.

PMID- 23007238
TI  - Immunoglobulin g from breast cancer patients regulates MCF-7 cells migration and
      MMP-9 activity by stimulating muscarinic acetylcholine receptors.
AB  - PURPOSE: We have previously reported the expression of muscarinic acetylcholine
      receptors (mAChR) in human breast tumors. The activation of these receptors
      triggered tumor cell proliferation. Considering that invasion and metastasis is
      the major cause of death in cancer, we investigated the action of autoantibodies
      against mAChR derived from breast cancer patients in stage I (T1N0Mx-IgG) on MCF
      7 cells migration and metalloproteinase-9 (MMP-9) activity. We also analyzed the
      participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.
      METHODS: Immunoglobulin G (IgG) was purified by chromatography in protein G
      agarose from blood samples of breast cancer patients obtained under informed
      consent. Migration was assayed by an in vitro wound assay. MMP-9 activity was
      quantified by zymography. RESULTS: T1N0Mx-IgG promoted tumor cell migration and
      increased MMP9 activity mimicking the action of the muscarinic agonist carbachol.
      This effect was reduced not only by the presence of atropine but also by 4-DAMP
      or tropicamide, antagonists for M(3) and M(4) mAChR subtypes respectively. The
      actions of T1N0Mx-IgG and carbachol on MCF-7 cells, involved the participation of
      phospholipase C/nitric oxide synthase/protein kinase C pathway. CONCLUSIONS: IgG
      from breast cancer patients in stage I could be promoting tumor progression by
      regulating migration and MMP-9 activity in tumor cells via mAChR activation. The
      presence of these autoantibodies could be determining the prognosis of breast
      cancer in these patients.

PMID- 23007239
TI  - National and local medication error reporting systems: a survey of practices in
      16 countries.
AB  - OBJECTIVES: To explore the existence and characteristics of national and local
      medication error reporting (MER) systems and to describe national medication
      safety experts' perceptions of a good and effective MER system and barriers to
      reporting. METHODS: In a descriptive cross-sectional study, 32 medication safety
      experts were identified through member organizations of the International
      Pharmaceutical Federation in 88 countries and other professional organizations in
      3 additional countries. These experts were invited to participate in an online
      survey. RESULTS: Sixteen national medication safety experts from different
      countries participated in the study (response rate, 50%). A national (n = 5) or
      local (n = 6) MER system existed in 11 of these countries. In 5 countries, no MER
      system existed. The most common features of the MER systems were confidentiality
      of the reported information and providing feedback to those involved in
      reporting. Most experts perceived that a good and effective MER system was
      characterized by the opportunity to learn from errors by those involved in
      reporting, having a nonpunitive approach to reporting, and ease of use. They also
      perceived that a blame culture, lack of time, training, and coordination of
      reporting were the main barriers to reporting. CONCLUSIONS: Blame culture, a lack
      of time, training and coordination of reporting continue to be the major barriers
      to reporting. Learning from errors and having a nonpunitive approach to reporting
      were thought to be the most critical features of a MER system. Difficulties in
      identifying national medication safety experts indicates a need for promoting
      international networking of medication safety experts and bodies for sharing
      information and learning from others.

PMID- 23007240
TI  - Patient involvement in patient safety: the health-care professional's
      perspective.
AB  - BACKGROUND: Despite increasing recognition that patients could play an important
      role in promoting the safety of their care, little is known on this issue
      regarding health-care professionals' (HCPs') attitudes toward patient
      involvement. OBJECTIVES: To investigate physicians' and nurses' attitudes toward
      patient involvement in safety-related behaviors, both through their eyes as a
      health-care professional and as a potential patient. DESIGN: Cross-sectional
      exploratory study using 2 surveys. Survey 1 addressed HCPs' attitudes toward
      supporting patient participation in safety-related behaviors. Survey 2 addressed
      HCPs' reported willingness to participate in safety-related behaviors (as a
      patient). PARTICIPANTS: Eighty health-care professionals (40 physicians and 40
      nurses) from an inner city London teaching hospital. FINDINGS: Attitudes were
      affected by the type of behavior, who the HCP is interacting with, and the
      participants own professional role. Overall, both professions held positive
      attitudes toward patient involvement, although in general, nurses versus
      physicians were more willing to both support patient involvement and participate
      themselves as a patient. CONCLUSION: Compared with other research on "lay"
      patients' attitudes, our data suggest that when HCPs are patients in hospital,
      they may be more willing to participate in safety-related behaviors. Promisingly,
      our data also suggest HCPs are willing to support patient involvement in safety
      related behaviors, which may suggest they are happy to participate in
      interventions aimed at encouraging patient involvement in this area. Further in
      depth research is needed to investigate the roles that HCPs (as both a patient
      and HCP) believe are appropriate for patients to participate in, under what
      circumstances and why.

PMID- 23007241
TI  - Introduction of checklists at daily progress notes improves patient care among
      the gynecological oncology service.
AB  - OBJECTIVES: To evaluate the impact of the introduction of checklists at the daily
      progress note to improve patient care among gynecologic oncology patients.
      METHODS: A progress note incorporating checklists that were pertinent for our
      patient population was developed with input obtained from all staff involved on
      patients care. The form was approved by the hospital. The average length of stay,
      compliance with prophylactic guidelines (anticoagulation, peptic ulcer disease),
      reason for admission, and readmission rate were compared among the
      preimplementation and postimplementation periods. RESULTS: A total of 492
      discharge summaries were evaluated through the study period (267 for the
      preimplementation period and 225 for the postimplementation period). The mean
      length of stay was of 4.46 days for the preimplementation and 3.46 days for the
      postimplementation period (P = 0.007). TEDs/SCDs were not used in 9.3% of the
      patients in the pre group versus 0.6% in the post group (P < 0.001). DVT
      prophylaxis was given to 30.1% of the pre group versus 34.8% of the post group (P
      = 0.0013). The administration of PUD prophylaxis also increased from 28.3% in the
      pre group to 40.2% of the post group (P < 0.001). There was a decrease in the
      nonsurgical admissions from 22.2% in the pre group versus 14.6% in the post group
      (P = 0.049). CONCLUSIONS: The use of checklists in daily progress notes enhances
      patient care by improving the delivery of routine care that is often overlooked
      in the light of major medical issues.

PMID- 23007242
TI  - Barriers and facilitators to communicating nursing errors in long-term care
      settings.
AB  - OBJECTIVE: To explore nurses' perceptions about communicating nursing errors.
      DESIGN: Cross-sectional, descriptive study. PARTICIPANTS: Approximately 289
      nurses working in long-term care facilities in Ontario, Canada. METHODS: A cross
      sectional, descriptive study of approximately 289 nurses working in long-term
      care facilities in Ontario, Canada. Solicited nurses' perceptions concerning the
      disclosure of nursing errors and adverse events by including an open-ended item
      at the conclusion of a 60-item (multiple choice) questionnaire on the same topic.
      A qualitative content analysis was conducted using a multi-step process. RESULTS:
      A total of 245 responses were included in the content analysis. The main
      categories related to error communication that were derived from the analysis
      were as follows: (1) differences in the definition of terms; (2) the day-to-day
      working conditions and their impact on defining and reporting errors; (3)
      organizational factors that both help and hinder the reporting of errors in
      ensuring both personal and organizational responsibility; (4) communication
      styles that both help and hinder disclosure and adherence to proper protocols;
      and (5) external factors such as policies and professional standards and codes of
      ethics, which can provide clarity of process; and (6) recommendations for
      implementation of professional standards in long-term care settings to facilitate
      supportive working conditions. CONCLUSION: Eliminating the barriers to error
      communication requires moving toward a culture of safety. This involves both top
      down and bottom-up approaches that allow nurses to feel comfortable being active
      participants in the error communication process.

PMID- 23007243
TI  - Public perceptions and preferences for patient notification after an unsafe
      injection.
AB  - BACKGROUND: Unsafe injection practices in health-care settings often result in
      notification of potentially affected patients, to disclose the error and
      recommend blood-borne pathogens testing. Few studies have assessed public
      perceptions and preferences for patient notification. METHODS: Six focus groups
      were conducted during Fall 2009, with residents of Atlanta, GA, and New York
      City, NY. Questions focused on preferences for receiving health information,
      knowledge of safe injection practices, and responses to and preferences for a
      patient notification letter. A mixed-method analysis was performed for
      qualitative themes and descriptive statistics. RESULTS: A total of 53 individuals
      participated; only 2 had ever heard of the term safe injection practices. After
      identification of unsafe injection practices, participants preferred to be
      notified via telephone, letter/mailing, email, or face-to-face from the facility
      where the incident occurred. More than 25 different types of information were
      mentioned as elements to be placed in a patient notification letter including:
      corrective actions by the facility, course of action for the patient, assurance
      of medical coverage, and how it happened/reason for the incident. Participants
      preferred that the tone of the letter be empathetic; nearly all indicated it was
      "very likely" that they would seek testing if notified. CONCLUSIONS: Facilities
      and health departments should strive to assure the notification process is
      conducted swiftly, clearly guiding affected patients to the necessary course of
      action. Notification letters are not "one size fits all," and some preferences
      expressed by patients may not be feasible in all situations. Prevention efforts
      should be complemented by research on improving effective patient communications
      when unsafe injection practices necessitate patient notification.

PMID- 23007244
TI  - Workplace engagement and workers' compensation claims as predictors for patient
      safety culture.
AB  - OBJECTIVE: Demonstrate the relationship between employee engagement and workplace
      safety for predicting patient safety culture. INTRODUCTION: Patient safety is an
      issue for the U.S. health-care system, and health care has some of the highest
      rates of nonfatal workplace injuries. Understanding the types of injuries
      sustained by health-care employees, the type of safety environment employees of
      health-care organizations work in, and how employee engagement affects patient
      safety is vital to improving the safety of both employees and patients. METHODS:
      The Gallup Q survey and an approved, abbreviated, and validated subset of
      questions from the Hospital Survey on Patient Safety Culture were administered to
      staff at a large tertiary academic medical center in 2007 and 2009. After
      controlling for demographic variables, researchers conducted a longitudinal,
      hierarchical linear regression analysis to study the unique contributions of
      employee engagement, changes in employee engagement, and employee safety in
      predicting patient safety culture. RESULTS: Teams with higher baseline
      engagement, more positive change in engagement, fewer workers' compensation
      claims, and fewer part-time associates in previous years had stronger patient
      safety cultures in 2009. Baseline engagement and change in engagement were the
      strongest independent predictors of patient safety culture in 2009. Engagement
      and compensation claims were additive and complimentary predictors, independent
      of other variables in the analysis, including the demographic composition of the
      workgroups in the study. CONCLUSIONS: A synergistic effect exists between
      employee engagement and decreased levels of workers' compensation claims for
      improving patient safety culture. Organizations can improve engagement and
      implement safety policies, procedures, and devices for employees with an ultimate
      effect of improving patient safety culture.

PMID- 23007245
TI  - Speaking up and sharing information improves trainee neonatal resuscitations.
AB  - OBJECTIVES: To identify teamwork behaviors associated with improving efficiency
      and quality of simulated resuscitation training. METHODS: Secondary analysis of a
      randomized controlled trial of trainees undergoing neonatal resuscitation
      training was performed. Trainees at a large academic center (n = 100) were
      randomized to receive standard curriculum (n = 36) versus supplemental team
      training curriculum (n = 62). A 2-hour team training session focused on
      communication skills, and team behaviors served as the intervention. Outcomes of
      interest included resuscitation duration, time required to complete a simulated
      newborn resuscitation, and performance score, determined by evaluation of each of
      the team's steps during simulated resuscitation scenarios. RESULTS: The teamwork
      behaviors assertion and sharing information were associated with shorter
      resuscitation duration and higher performance scores. Each additional use of
      assertion (per minute) was associated with a duration reduction of 41 s (95%
      confidence interval [CI], -71.5 to -10.2) and an increase in performance score of
      1.6% (95% CI, 0.4-2.7). Each additional use of sharing information (per minute)
      was associated with a 14-second reduction in duration (95% CI, -30.4 to 2.9) and
      a 0.8% increase in performance score (95% CI, 0.05-1.5). CONCLUSIONS: Teamwork
      behaviors of assertion and sharing information are 2 important mediators of
      efficiency and quality of resuscitations.

PMID- 23007246
TI  - Relationships of multitasking, physicians' strain, and performance: an
      observational study in ward physicians.
AB  - BACKGROUND: Simultaneous task performance ("multitasking") is common in hospital
      physicians' work and is implicated as a major determinant for enhanced strain and
      detrimental performance. OBJECTIVE: The aim was to determine the impact of
      multitasking by hospital physicians on their self reported strain and
      performance. METHOD: A prospective observational time-and-motion study in a
      Community Hospital was conducted. Twenty-seven hospital physicians (surgical and
      internal specialties) were observed in 40 full-shift observations. Observed
      physicians reported twice on their self-monitored strain and performance during
      the observation time. Associations of observed multitasking events and subsequent
      strain and performance appraisals were calculated. RESULTS: About 21% of the
      working time physicians were engaged in simultaneous activities. The average time
      spent in multitasking activities correlated significantly with subsequently
      reported strain (r = 0.27, P = 0.018). The number of instances of multitasking
      activities correlated with self-monitored performance to a marginally significant
      level (r = 0.19, P = 0.098). CONCLUSION: Physicians who engage in multitasking
      activities tend to self-report better performance but at the cost of enhanced
      psychophysical strain. Hence, physicians do not perceive their own multitasking
      activities as a source for deficient performance, for example, medical errors.
      Readjustment of workload, improved organization of work for hospital physicians,
      and training programs to improve physicians' skills in dealing with multiple
      clinical demands, prioritization, and efficient task allocation may be useful
      avenues to explore to reduce the potentially negative impact of simultaneous task
      performance in clinical settings.

PMID- 23007247
TI  - Bacterial chitin utilisation at extremely haloalkaline conditions.
AB  - Chitin is produced in large amounts in hypersaline habitats with neutral pH due
      to the high biomass production of brine shrimp Artemia. Recently, a high
      abundance of Artemia was also noticed in hypersaline soda lakes in the Kulunda
      Steppe (Altai, Russia), which prompted us to survey the possibility of microbial
      chitin utilization at extremely haloalkaline conditions in soda brines. Most
      active chitin utilisation-supporting microbial growth was found at anaerobic
      conditions at pH 10 and up to 3.5 M total Na(+). At aerobic conditions, the
      degradation of chitin was slower, mostly incomplete and active at <2 M total
      Na(+), although very slow partial degradation was possible up to 4 M Na(+).
      Anaerobic enrichments at pH 10 yielded two different groups of obligately
      haloalkaliphilic fermentative anaerobes, exclusively specialized to utilise
      insoluble chitin as the only growth substrate. One group was represented by a
      single strain growing at moderate salinity, and another comprised multiple
      isolates growing up to 3.5 M Na(+). These groups represent two novel bacterial
      phyla not closely related to any other cultured bacteria. Aerobic enrichments
      from the lake sediments were dominated by several obligately haloalkaliphilic
      members of the genus Marinimicrobium in the Gammaproteobacteria. They were less
      specialised than the anaerobes and grew with chitin and its monomer and oligomers
      at a pH of 10 up to 2.5 M Na(+). Furthermore, several strains of haloalkaliphilic
      Gram-positive chitinolytics belonging to bacilli and actinobacteria were isolated
      from soda lake sediments and surrounding soda soils. In general, the results
      indicate the presence of an active and diverse haloalkaliphilic chitinolytic
      microbial community in hypersaline soda habitats.

PMID- 23007248
TI  - Pelvic inflammatory disease (PID) from Chlamydia trachomatis versus PID from
      Neisseria gonorrhea: from clinical suspicion to therapy.
AB  - Pelvic inflammatory disease (PID) is the most significant complication of
      sexually transmitted infections in childbearing-age women and it represents an
      important public health problem because of its long-term sequelae (chronic pelvic
      pain, tubal infertility, ectopic pregnancy). Prior to the mid 1970s PID was
      considered a monoetiologic infection, due primarily to Neisseria gonorrhea. Now
      it is well documented as a polymicrobial process, with a great number of
      microrganisms involved. In addition to Neisseria gonorrhea and Chlamydia
      trachomatis, other vaginal microrganisms (anaerobes, Gardnerella vaginalis,
      Haemophilus influenzae, enteric Gram negative rods, Streptococco agalactie,
      Mycoplasma genitalium) also have been associated with PID. There is a wide
      variation in PID clinical features; the type and severity of symptoms vary by
      microbiologic etiology. Women who have chlamydial PID seem more likely than women
      who have gonococcal PID to be asymptomatic. Since clinical diagnosis is
      imprecise, the suspicion of PID should be confirmed by genital assessment for
      signs of inflammation or infection, blood test and imaging evaluation.
      Laparoscopic approach is considered the gold standard. According to the
      polymicrobial etiology of PID, antibiotic treatment must provide broad spectrum
      coverage of likely pathogens. Early administration of antibiotics is necessary to
      reduce the risk of long-term sequelae.

PMID- 23007249
TI  - Looking for an asymptomatic infection: usefulness of screening for Chlamydia
      trachomatis and genital herpes.
AB  - Chlamydia trachomatis (CT) and Herpes simplex virus type 2 (HSV-2) genital
      infections are among the more frequent sexually transmissible infections with
      different prevalence by age, populations and geographical areas. Both are
      widespread, have an asymptomatic latent stage detectable only by laboratory and
      can have serious consequences such as tubal infertility and neonatal herpes. The
      direct isolation of CT in cervical or urethral discharge through Nucleic Acid
      Amplification Test (NAATs) allows to detect and to treat the infection with
      effective antibiotic medication. The screening of all women younger than 25 year
      old showed to be effective in reducing tubal complications but not in decreasing
      the incidence of the infection in the general population. Only a proactive
      screening of younger women, repeated yearly and associated with an effective
      partner notification could achieve a decrease of the incidence rate in the
      general population. The detection of type specific herpetic antibodies allows to
      identify persons with herpetic infection regardless of symptoms. While a
      population-based screening of general population cannot be proposed at the
      moment, a selective screening (attenders of STI clinic, HIV-positive patients,
      pregnant women) is a debated issue between those who consider it an effective
      means to detect persons with unrecognized symptoms who are infectious and those
      who think that preventive measures and antiviral medication are not effective
      enough to be proposed.

PMID- 23007250
TI  - The challenges of a neglected STI: Molluscum contagiosum.
AB  - Molluscum Contagiosum (MC) virus, a DNA Poxvirus, is responsible for benign
      infection of the skin epidermal layer and mucous membranes named MC. The lesions
      are small papules with typical central depressions or umbilications, that contain
      a waxy, curd-like core. The condition is most common in children, but during the
      last 25 years has become more common in young adults and immuno-compromised
      adults, especially in HIV/AIDS. Although molluscum contagiosum infections are
      considered a nuisance rather than a serious heath problem, the rising incidence
      in young , sexually active adults, suggests a transmission during sexual activity
      and can be regarded as a marker for the presence of other STIs. Even though some
      Authors don't recommend any treatment for cutaneous, non genital molluscum
      contagiosum in healthy people, treatment of genital molluscum contagiosum lesions
      is recommended in order to reduce the risk of sexual transmission, prevent
      autoinoculation, and increase patients quality of life.

PMID- 23007251
TI  - The genital herpes problem in pregnancy.
AB  - Genital herpes is a common sexually transmitted infection. In reproductive age it
      involves the additional risk of vertical transmission to the neonate. Rates of
      transmission are affected by the viral type and whether the infection around
      delivery is primary or recurrent. Neonatal herpes is a rare but very severe
      complication of genital herpes infection and is caused by contact with infected
      genital secretions at the time of labor. Maternal acquisition of herpes simplex
      virus (HSV) in the third trimester of pregnancy carries the highest risk of
      neonatal transmission. Prevention of neonatal herpes depends on preventing
      acquisition of genital HSV infection during late pregnancy and avoiding exposure
      of the infant to herpetic lesions during delivery. Uninfected woman should be
      counselled about the need of avoiding sexual contact during the third trimester.
      Elective caesarean section before the onset of labor is the choice mode of
      delivery for women with genital lesions or with prodromal symptoms near the term,
      even if it offers only a partial protection against neonatal infection. Antiviral
      suppressive therapy is used from 36 weeks of gestation until delivery in pregnant
      women with recurrences to prevent genital lesions at the time of labor so
      reducing the need of caesarean sections. Currently, routine maternal serologic
      screening is not yet recommended. Because most mothers of infants who acquire
      neonatal herpes lack histories of clinically evident genital herpes, researchers
      should focus on the recognition of asymptomatic primary genital HSV infections.

PMID- 23007252
TI  - Off label treatments of genital warts: the role of photodynamic therapy.
AB  - Conventional therapies for genital warts, the clinical expression of low-risk
      human papillomavirus (HPV) anogenital infection, are not targeted antiviral
      therapies, but either attempt physical removal of the lesion or induce
      inflammation and a bystander immune response. Moreover, very few of the current
      treatments have been tested by rigorous blinded, randomized controlled trials.
      Therefore, official recommendations are often associated with unsatisfactory
      response rates and high recurrence rates. It is the purpose of this review to
      provide a brief overview of the genital wart treatment literature to expand
      awareness of the options available to practitioners faced with patients
      presenting with this disease. Particular attention will be paid to unconventional
      and complementary therapies (the so called "off-label" treatments) among which
      photodynamic therapy has been recently introduced as a promising strategy to both
      guarantee clearance of the lesion and eradication of the virus itself. Mechanisms
      of action of PDT are discussed together with a summary of clinical and
      experimental available evidences.

PMID- 23007253
TI  - Herpes genitalis without frontiers: from clinical aspects to viral
      identification.
AB  - Genital herpes simplex virus infection is a recurrent, lifelong disease with no
      cure. The strongest predictor for infection is a person's number of lifetime sex
      partners. HSV-2 is the commonest responsible, although infections caused by HSV-1
      are rapidly increasing, particularly in adolescents, women and men who have sex
      with men. The natural history includes first-episode of mucocutaneous infection,
      establishment of latency in the dorsal root ganglion, and subsequent
      reactivation. Most infections are transmitted via asymptomatic viral shedding.
      Atypical manifestations are common. Genital HSV-2 recurs six times more
      frequently than type 1. Laboratory confirmation of the clinical diagnosis is
      recommended in all patients in order to guide a correct counselling and
      management. Real-time PCR and viral culture represent the gold standard for
      diagnosis. Serologic testing can be useful in persons with a questionable
      history. Counselling patients about the risk of transmission is crucial and helps
      prevent the spread of disease and neonatal complications.

PMID- 23007254
TI  - Attitude to treatment of patients with psoriasis attending spa center.
AB  - AIM: The aim of this paper was to investigate beliefs and preferences towards
      treatment of patients with psoriasis attending Comano SPA (Trentino, Italy) in
      comparison to patients referring to the University Hospital of Verona. METHODS:
      Patient with psoriasis referring to Comano SPA and to the University Hospital of
      Verona were visited, their clinical data were collected and they were
      administered a questionnaire investigating their knowledge about psoriasis, as
      well as their attitude and preferences towards conventional therapies and SPA
      treatments. RESULTS: [Corrected] A total of 288 patients with chronic plaque
      psoriasis were recruited, 169 from Comano SPA and 119 from Verona Hospital. There
      were no differences regarding demographic data, severity of psoriasis, impact on
      quality of life and prevalence of cardio-metabolic comorbidities between the two
      groups. SPA patients more rarely believed that pharmacological treatments are
      safe and effective (6.5% vs. 21.8% P=0.001), had less trust in physician (32.5%
      vs. 67.2%; P=0.001) and preferred alternative therapies like balneotherapy
      compared to hospital patients (55.6% vs. 30.3%; P=0.0001), because they assumed
      they were more safe and effective than systemic drugs (37.3% vs. 1.7%; P=0.001).
      SPA patients preferred living with psoriasis rather than taking drugs to treat it
      more commonly than hospital patients (26.6% vs. 5%; P=0.001). CONCLUSION:
      Patients attending a SPA centre tend to trust conventional drug treatments less
      often than those attending a hospital clinic, and prefer balneotherapy as a
      dedicated alternative therapy. Fear of adverse events is a major concern among
      patients with psoriasis, especially those attending a SPA center.

PMID- 23007255
TI  - Efficacy and tolerability of topical 0.2% Myrtacine(r) and 4% vitamin PP for
      prevention and treatment of retinoid dermatitis in patients with mild to moderate
      acne.
AB  - AIM: The aim of the present study was to evaluate the efficacy and tolerability
      of an emulsion of 0.2% Myrtacine(r) and 4% vitamin PP, compared with a simple
      emollient cream, in the treatment of retinoid dermatitis in patients with mild-to
      moderate acne. METHODS: This was a prospective, multicenter, open-label, non
      randomised, parallel-group study. Patients (age 12-49 years; skin phototype I-IV)
      with mild-to-moderate acne, who were treated with a topical retinoid for at least
      one month and had developed skin irritation were assigned to one of the two
      following treatments: 0.2% Myrtacine(r) and 4% vitamin PP (N.=116) or a simple
      emollient cream (N.=48). Both treatments were administered twice daily, 1-1.5
      hours after the application of the topical retinoid. Study endpoints were
      improvement in signs and symptoms of retinoid dermatitis, global efficacy,
      reduction in acne severity, overall clinical outcome, patient satisfaction and
      tolerability. RESULTS: At day 28, compared with the simple emollient cream, 0.2%
      Myrtacine(r) and 4% vitamin PP significantly decreased signs (erythema,
      dryness/scaling, oedema, and roughness) and symptoms (itching, stinging, burning
      sensation and discomfort) of retinoid dermatitis (P<0.01). In addition, compared
      with the simple emollient cream, 0.2% Myrtacine(r) and 4% vitamin PP decreased
      acne severity in a significantly greater proportion of patients (P=0.023) and was
      associated with a better clinical outcome (mild, intermediate, clinically
      relevant or global improvement; P<0.001). 0.2% Myrtacine(r) and 4% vitamin PP was
      also associated with greater patient satisfaction and was better tolerated than
      the simple emollient cream. CONCLUSION: 0.2% Myrtacine(r) and 4% vitamin PP was
      effective and well tolerated in the treatment of retinoid dermatitis in patients
      with mild-to-moderate acne and significantly improved acne severity and overall
      clinical outcome.

PMID- 23007256
TI  - Systemic lupus erythematosus developing immediately after necrotizing fasciitis.
AB  - Necrotizing fasciitis (NF) is a medical-surgical emergency characterized by
      severe bacterial infection that affects the subcutaneous tissue and spreads to
      the underlying fascia; usually it is caused by penetrating trauma, sometimes by
      surgical therapy, very rarely by minor insults such as insect bites. Systemic
      lupus erythematosus (SLE) is a potentially fatal autoimmune disease involving
      virtually all the key components of the immune system. Although cases of post
      infection autoimmunity were already described, a literature search using Pub Med
      and Medline revealed that SLE was never reported to occur in patients affected,
      immediately before, with NF. We observed and herein report, however, a case of a
      woman showing an insect-bite-induced NF, which was immediately followed by the
      development of a SLE. In conclusion, this case of postinfection autoimmunity
      provides early evidence of a patient developing SLE immediately after NF, and
      suggests that caution in the follow-up of NF is necessary, because NF might favor
      the development of a severe autoimmunity.

PMID- 23007257
TI  - Mesenchymal hamartoma of the tongue.

PMID- 23007258
TI  - Topical imiquimod in the treatment of large facial keratoacanthomas.

PMID- 23007259
TI  - Cutaneous melanoma in husband and wife.

PMID- 23007260
TI  - Ethical responsibility when dermatological signs reflect genetic disease.

PMID- 23007261
TI  - Localized vascular lesions of the glans in patients with lichen sclerosus
      diagnosed by dermatoscopy.

PMID- 23007262
TI  - Cytochrome P450-catalyzed O-dealkylation coupled with photochemical NADPH
      regeneration.
AB  - Cytochrome P450 monooxygenases are multifunctional enzymes with potential
      applications in chemoenzymatic synthesis of complex chemicals as well as in
      studies of metabolism and xenobiotics. Widespread application of cytochrome
      P450s, however, is encumbered by the critical need for redox equivalents in their
      catalytic function. To overcome this limitation, we studied visible light-driven
      regeneration of NADPH for P450-catalyzed O-dealkylation reaction; we used eosin Y
      as a photosensitizing dye, triethanolamine as an electron donor, and
      [Cp*Rh(bpy)H2O] as an electron mediator. We analyzed catalytic activity of cell
      free synthesized P450 BM3 monooxygenase variant (Y51F/F87A, BM3m2) in the
      presence of key components for NADPH photoregeneration. The P450-catalyzed O
      dealkylation reaction sustainably maintained its turnover with the continuous
      supply of photoregenerated NADPH. Visible light-driven, non-enzymatic NADPH
      regeneration provides a new route for efficient, sustainable utilization of P450
      monooxygenases.

PMID- 23007263
TI  - Low cost integration of 3D-electrode structures into microfluidic devices by
      replica molding.
AB  - We demonstrate a new replica molding method for integrating 3D-composite
      electrodes into microfluidic devices made from polydimethylsiloxane (PDMS) at low
      cost. Our process does not require work in a cleanroom, expensive materials, or
      expensive equipment once a micro mold has been fabricated using standard
      multilayer SU-8 photolithography. Different device geometries have been
      fabricated to demonstrate the capabilities and limitations of the method. The
      electrical properties of the composite electrode material are characterized.
      Furthermore, a device for concentrating particles via AC-dielectrophoresis is
      presented as an example for a potential application of the fabrication process.

PMID- 23007264
TI  - Use of new-generation oral anticoagulant agents in patients receiving
      antiplatelet therapy after an acute coronary syndrome: systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Despite receipt of dual antiplatelet therapy, patients after an acute
      coronary syndrome (ACS) remain at significant risk for thrombotic events. The
      role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors
      is debated in this setting. Our study objective was to evaluate the efficacy and
      safety of new-generation oral anticoagulant agents compared with placebo in
      patients receiving antiplatelet therapy after an ACS. METHODS: Electronic
      databases were searched to identify prospective randomized placebo-controlled
      clinical trials that evaluated the effects of anti-Xa or direct thrombin
      inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy
      measures included stent thrombosis, overall mortality, and a composite end point
      of major ischemic events, while thrombolysis in myocardial infarction-defined
      major bleeding events were used as a safety end point. The net clinical benefit
      was calculated as the sum of composite ischemic events and major bleeding events.
      RESULTS: For the period January 1, 2000, through December 31, 2011, we identified
      7 prospective randomized placebo-controlled clinical trials that met the study
      criteria, involving 31 286 patients. Based on the pooled results, the use of new
      generation oral anticoagulant agents in patients receiving antiplatelet therapy
      after an ACS was associated with a dramatic increase in major bleeding events
      (odds ratio, 3.03; 95% CI, 2.20-4.16; P < .001). Significant but moderate
      reductions in the risk for stent thrombosis or composite ischemic events were
      observed, without a significant effect on overall mortality. For the net clinical
      benefit, treatment with new-generation oral anticoagulant agents provided no
      advantage over placebo (odds ratio, 0.98; 95% CI, 0.90-1.06; P = .57).
      CONCLUSION: The use of anti-Xa or direct thrombin inhibitors is associated with a
      dramatic increase in major bleeding events, which might offset all ischemic
      benefits in patients receiving antiplatelet therapy after an ACS.

PMID- 23007265
TI  - Complex interaction between serum folate levels and genetic polymorphisms in
      folate pathway genes: biomarkers of prostate cancer aggressiveness.
AB  - Little is known about the role of folate and polymorphisms associated with folate
      metabolism on prostate cancer risk in populations of African origin. We examined
      the relationship between serum folate and prostate cancer and whether any
      association was modified by genetic polymorphisms for folate metabolism. The
      study was case-control in design and consisted of 218 men 40-80 years old with
      newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men
      attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate
      was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T
      and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate
      concentration was higher among cases (12.3 +/- 4.1 nmol/L) than controls (9.7 +/-
      4.2 nmol/L). Serum folate concentration showed a positive association with
      prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10 nmol/L) regardless of grade. No
      interactions were observed between genotype and folate concentration, but a weak
      gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger
      studies to investigate the role of gene-gene/gene-diet interactions in Black men
      are needed.

PMID- 23007266
TI  - Immunotherapy: HEV: the gateway to tumour control?

PMID- 23007269
TI  - Breast cancer: Radiation risk in BRCA carriers.

PMID- 23007270
TI  - Haematological cancer: Hit the lymphoma, JAK.

PMID- 23007271
TI  - Cancer-treatment toxicity: can nutrition help?

PMID- 23007275
TI  - Competency requirements for middle and senior managers in community health
      services.
AB  - The Australian health system has been subjected to rapid changes in the last 20
      years to meet increasingly unmet health needs. Improvement of the efficiency and
      comprehensiveness of community-based services is one of the solutions to reducing
      the increasing demand for hospital care. Competent managers are one of the key
      contributors to effective and efficient health service delivery. However, the
      understanding of what makes a competent manager, especially in the community
      health services (CHS), is limited. Using an exploratory and mixed-methods
      approach, including focus group discussions and an online survey, this study
      identified five key competencies required by senior and mid-level CHS managers in
      metropolitan, regional and rural areas of Victoria: Interpersonal, communication
      qualities and relationship management; Operations, administration and resource
      management; Knowledge of the health care environment; Leading and managing
      change; and Evidence-informed decision-making. This study confirms that core
      competencies do exist across different management levels and improves our
      understanding of managerial competency requirements for middle to senior CHS
      managers, with implications for current and future health service management
      workforce development. 

PMID- 23007273
TI  - Stereotactic body radiotherapy treatment of extracranial metastases.
AB  - Radiotherapy is an integral treatment for patients with metastatic cancer,
      although it is usually reserved for palliation of pain, dyspnoea, oedema,
      bleeding and neurological symptoms. However, the administration of high-precision
      radiotherapy, termed stereotactic body radiotherapy (SBRT), has the potential to
      significantly affect the disease course for some patients with metastatic cancer
      by delivering high doses of radiation to the secondary tumours with limited high
      dose delivery to adjacent healthy tissues. Indeed, such accurate delivery has
      been firmly established as a therapy for medically inoperable early-stage non
      small-cell lung cancer. To date, the technique has demonstrated improvements in
      controlling metastasis and, in some cases, improved palliation compared with
      conventionally fractionated radiotherapy. Active areas of research in SBRT
      include patient selection for curative intent, optimization of SBRT planning
      techniques, dosing schema and integration of SBRT into systemic therapies. Given
      the improvements in cytotoxic and targeted therapies over the past decade,
      studies testing the careful integration of SBRT into standard systemic therapy
      regimens are needed. Further investigations are also needed to understand the
      basic biological mechanisms underlying SBRT because they are likely to be
      different to those mechanisms in conventional radiotherapy.

PMID- 23007276
TI  - Assessment of maximum weight change and duration of therapeutic effect for non
      surgical treatment of obesity using an exponential model.
AB  - Efficacy of weight loss and maintenance therapies in obesity is difficult to
      quantify due to continuous weight changes over time. We assessed a single
      exponential model of weight changes during selected non-surgical therapies of non
      diabetic obese subjects. We analyzed published mean weight data from 6 studies of
      >=12 weeks duration, with comparable treatment groups, and >=4 weight
      measurements during very low carbohydrate or fat diets, or treatment with
      Lorcaserin, Sibutramine or Orlistat. We fit data to a single exponential model to
      estimate maximum predicted weight loss or regain and duration of weight loss or
      regain for each therapy. A single exponential is the appropriate model as
      determined by Kolmogorov-Smirnov, constant variance, and Durbin-Watson tests.
      Validity of parameter estimates was indicated by coefficients of variation <25%.
      Sensitivity analysis showed that weight regain at the end of the weight loss
      phase affected parameter estimates in some instances, with variations of weight
      loss of 0.2-0.7% of basal. Estimated weight loss and regain were similar to
      observed weight changes in all studies. The model could also be used to assess
      dose-response relationships. Estimates from the model were used to compare
      concurrent obesity regimens using 95% confidence intervals, taking into account
      pre-determined minimal clinically important differences. This exponential model
      may provide accurate estimates of maximum achievable weight loss or regain and
      optimal duration of efficacy for a variety of non-surgical weight loss and
      maintenance regimens from published mean weight data and may be useful to more
      accurately evaluate weight loss and maintenance regimens.

PMID- 23007277
TI  - Revised IPSS (IPSS-R) stratification and outcome of MDS patients treated with
      azacitidine.

PMID- 23007278
TI  - Snake venom toxin from Vipera lebetina turanica sensitizes cancer cells to TRAIL
      through ROS- and JNK-mediated upregulation of death receptors and downregulation
      of survival proteins.
AB  - We investigated whether snake venom toxin (SVT) from Vipera lebetina turanica
      enhances the apoptosis ability of tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a
      dose-dependent manner; however, this reduction did not occur in TRAIL resistant
      HT-29, A549 and HepG2 cells with an even higher dose of TRAIL. SVT, but not TRAIL
      enhanced expression of cell death receptor (DR) in TRAIL resistant cancer cells
      in a dose-dependent manner. A combination of SVT with TRAIL significantly
      inhibited cell growth of TRAIL resistant HT-29, A549 and HepG2 cells. Consistent
      with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was
      significantly increased as well as apoptosis related proteins such as cleaved
      caspase-3, -8, -9 and Bax. However, the expression of survival proteins (e.g.,
      cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of
      SVT and TRAIL. Depletion of DR4 or DR5 by small interfering RNA significantly
      reversed the cell growth inhibitory and apoptosis blocking effects of SVT in
      HCT116 and HT-29 cells. Pretreatment with the c-Jun N-terminal kinase (JNK)
      inhibitor SP600125 and the reactive oxygen species (ROS) scavenger N
      acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5
      expression, expression of the apoptosis related protein such as caspase-3 and-9,
      as well as cell growth inhibitory effects. The collective results suggest that
      SVT facilitates TRAIL-induced apoptosis in cancer cells through up-regulation of
      the TRAIL receptors; DR4 and DR5 via ROS/JNK pathway signals.

PMID- 23007279
TI  - Sublocalization of Rab23, a mediator of Sonic hedgehog signaling pathway, in
      hepatocellular carcinoma cell lines.
AB  - The novel member of the Rab family of GTPases, Rab23, is an essential negative
      regulator of the Sonic hedgehog (Shh) signaling pathway. Loss of function
      mutation of the Rab23 gene causes abnormal development of the neural tube in mice
      and in certain human congenital diseases. The aberrant overexpression of Rab23
      has been associated with various diseases, such as gastric, hepatocellular and
      lung cancer. The exact function of Rab23 in hepatocellular carcinomas (HCCs),
      however, remains unknown. Previously, we reported the abnormal sublocalization of
      Rab23 in lung cancers. In the current study, we investigated the role of Rab23 in
      HCCs. We report the distinct sublocalization pattern of Rab23 in HCC cell lines.
      This difference depends on the GDP/GTP-binding form, and inhibition of the Rab23
      cycle decreases the expression and nuclear localization of Gli1.

PMID- 23007280
TI  - Randomized controlled trial of emergency transjugular intrahepatic portosystemic
      shunt versus emergency portacaval shunt treatment of acute bleeding esophageal
      varices in cirrhosis.
AB  - BACKGROUND: Emergency treatment of bleeding esophageal varices (BEV) in cirrhosis
      is of paramount importance because of the resultant high mortality rate.
      Emergency therapy today consists mainly of endoscopic and pharmacologic measures,
      with use of transjugular intrahepatic portosystemic shunt (TIPS) when bleeding is
      not controlled. Surgical portosystemic shunt has been relegated to last resort
      salvage when all other measures fail. Regrettably, no randomized controlled
      trials have been reported in which TIPS and surgical portosystemic shunt were
      compared in unselected patients with acute BEV, with long-term follow-up. This is
      a report of a long-term prospective randomized controlled trial (RCT) that
      compared TIPS with emergency portacaval shunt (EPCS) in patients with cirrhosis
      and acute BEV. STUDY DESIGN: A total of 154 unselected, consecutive cirrhotic
      patients ("all comers") with acute BEV were randomized to TIPS (n = 78) or EPCS
      (n = 76), and the two treatments were compared with regard to effect on survival,
      control of bleeding, portal-systemic encephalopathy (PSE), and disability.
      Diagnostic workup was completed within 6 h and TIPS or EPCS was initiated within
      24 h. Regular follow-up was accomplished in 100 % of patients and lasted for 5 to
      10 years in 85 % and 3 to 4.5 years in the remainder. This report focuses on
      control of bleeding and survival. RESULTS: The clinical characteristics of the
      two groups were similar, and the distribution of Child classes A, B, and C was
      almost identical. TIPS was successful in controlling BEV for 30 days in 80 % of
      patients but achieved long-term control of BEV in only 22 %. In contrast, EPCS
      controlled BEV immediately in all patients and permanently in 97 % (p < 0.001).
      TIPS patients required almost twice as many units of blood transfusion as EPCS
      patients. Survival rate at all time intervals and in all Child classes was
      significantly greater following EPCS than after TIPS (p < 0.001). Median survival
      was over 10 years following EPCS, compared to 1.99 years following TIPS. Stenosis
      or occlusion of TIPS was demonstrated in 84 % of patients who survived 21 days,
      63 % of whom underwent TIPS revision, which failed in 80 %. In contrast, EPCS
      remained permanently patent in 97 % of patients. Recurrent PSE was threefold more
      frequent following TIPS than after EPCS (61 versus 21 %). CONCLUSIONS: EPCS was
      uniformly effective in the treatment of BEV, while TIPS was disappointing. EPCS
      accomplished long-term survival while TIPS resulted in a survival rate that was
      less than one fifth that of EPCS. The results of this RCT in unselected,
      consecutive patients justify the use of EPCS as a first-line emergency treatment
      of BEV in cirrhosis (clinicaltrials.gov #NCT00734227).

PMID- 23007282
TI  - Colosplenic fistula: a highly unusual colonic fistula.
AB  - DISCUSSION: Internal fistulization of the colon to other organs, such as the
      urinary bladder, vagina, or small bowel is a relatively common complication
      associated with inflammatory diseases such as diverticulitis, Crohn disease, as
      well as neoplasia such as colorectal cancer or lymphoma. However, fistulization
      of the colon to the spleen is an exceedingly rare condition described by few in
      the literature.

PMID- 23007281
TI  - Appendicolith delays resolution of appendicitis following nonoperative
      management.
AB  - INTRODUCTION: Success in nonoperative management is only based on the clinical
      symptoms of patients with acute appendicitis. However, imaging studies can
      provide further insight into the status of the appendix to monitor treatment
      response if immediate appendectomy is not undertaken. This study investigates
      sonographic resolution following nonoperative management and assesses the
      feasibility of incorporating ultrasound into patient care. MATERIALS AND METHODS:
      Adult patients with acute appendicitis who had been successfully treated with
      nonoperative management were enrolled and received repeat sonographic
      examinations using 3-day intervals until sonographic resolution. The relationship
      between the time to achieve sonographic resolution and clinical parameters was
      identified using negative binomial regression models. RESULTS: From January 2003
      to December 2009, 128 patients were successfully treated with nonoperative
      management. Eighty patients completed sonographic examinations until achieving
      resolution. Sonographic resolution was achieved on 17 +/- 12 days (range, 3-69
      days). Ninety-five percent of the patients achieved sonographic resolution within
      41 days. The appendicolith was positively related to the time to achieve
      sonographic resolution (rate ratios, 1.63; 95 % confidence intervals, 1.06-2.51).
      CONCLUSIONS: Ultrasound can be used to evaluate the condition of the appendix to
      monitor treatment response following nonoperative management on the sixth week.
      An appendicolith delays sonographic resolution of appendicitis.

PMID- 23007283
TI  - Feasibility and oncological outcomes of limited duodenal resection in patients
      with primary nonmetastatic duodenal GIST.
AB  - INTRODUCTION: Duodenal gastrointestinal stromal tumors (GISTs) are rare but still
      represent approximately 30 % of primary duodenal tumors. This study aimed to
      audit the feasibility and oncological outcomes of limited duodenal resection in
      patients with primary nonmetastatic duodenal GIST. METHODS: Twelve patients who
      underwent surgery at our institution since 2002 were prospectively followed up.
      The duodenal GISTs were located in the first (n = 3), second (n = 1), third (n =
      3), and fourth of duodenum (n = 1). Involving both D1/D2 (n = 2), D2/D3 (n = 1),
      and D3/D4 (n = 1). The primary endpoint for this analysis was disease-free
      survival. RESULTS: The commonest presentation was melena and anemia (83 %). All
      the patients underwent limited resection; six wedge resections with primary
      closures and six segmental resections with end-to-end anastomosis. The median
      tumor size was 8 cm (range, 5-16 cm). According to Fletcher scale, two GISTs were
      low risk, while 10 patients were intermediate and high risk. The latter received
      adjuvant therapy. All the patients had a complete resection with no postoperative
      mortality. One patient had three liver metastases 4 months after limited
      resection and had partial hepatectomy. After median follow-up of 45 (15-78)
      months, all patients are alive and disease free. CONCLUSION(S): When technically
      feasible, limited resection should be considered a reliable and curative option
      for duodenal GIST achieving satisfactory disease-free survival. The technical
      feasibility is guided by the tumor size, possible adjacent organ involvement, and
      its exact anatomical location.

PMID- 23007284
TI  - Significance of the inflammation-based Glasgow prognostic score for short- and
      long-term outcomes after curative resection of gastric cancer.
AB  - BACKGROUND: The Glasgow prognostic score (GPS) is a patient-related measure to
      determine long-term outcomes in cancer patients. This study examined the impact
      of GPS on outcomes including postoperative complications after curative resection
      of gastric cancer. METHODS: The systemic inflammatory response was assessed by
      GPS, and the severity of postoperative complications was evaluated according to
      the Clavien-Dindo classification. Survival analysis was performed by the Kaplan
      Meier method and the log rank test. Multivariate analysis was performed to
      determine significant associations with complications by a logistic regression
      model and the independent prognostic values by Cox's proportional hazards model.
      RESULTS: Study patients (n = 1017) were allocated as follows: 904 (88.9 %) to GPS
      0, 92 (9.0 %) to GPS 1, and 21 (2.1 %) to GPS 2. One hundred sixty-three patients
      (16.0 %) had postoperative complications of >= grade 2. Multivariate logistic
      analysis identified gender, body mass index, tumor location, tumor depth, blood
      transfusion, and comorbidity as significantly correlated with postoperative
      complications. However, GPS was not associated with the incidence of
      complication. On the other hand, multivariate analysis for overall survival
      identified GPS as an independent prognostic factor. CONCLUSIONS: GPS is a
      significant predictor of long-term survival in curable gastric cancer surgery but
      not of short-term outcomes.

PMID- 23007286
TI  - The diagnostic value of narrow-band imaging for the detection of nasopharyngeal
      carcinoma.
AB  - OBJECTIVES: To evaluate the diagnostic value of narrow-band imaging (NBI) for the
      detection of nasopharyngeal carcinoma (NPC). STUDY DESIGN: Prospective study.
      SETTING: Tertiary medical center. SUBJECTS AND METHODS: Between December 2009 and
      June 2010, a total of 1,854 patients were examined by means of an electronic
      nasopharyngolaryngoscope equipped with conventional white light (WL) and an NBI
      system. The sensitivity, specificity and positive/negative predictive values for
      detecting NPC were calculated and compared. RESULTS: Of these patients, 62 cases
      (3.34%) were pathologically confirmed as NPC. The sensitivity, specificity,
      positive predictive value and negative predictive value for detecting NPC
      significantly increased from 90.3, 75.4, 11.3 and 99.6% with WL up to 100, 99.2,
      81.6 and 100% with NBI, respectively. CONCLUSION: Our findings suggested that NBI
      endoscopy might serve as an ideal tool in the detection of NPC.

PMID- 23007285
TI  - PPI therapy and albumin are better predictors of recurrent Clostridium difficile
      colitis than choice of antibiotics.
AB  - BACKGROUND: Recurrent Clostridium difficile colitis (RCDC) is common, but data
      regarding recurrence rates and predisposing factors are sparse. METHODS: A
      retrospective case-control study was performed, identifying all inpatients and
      outpatients >=18 years of age with C. difficile colitis (CDC) confirmed by a
      positive stool sample collected at our institution from January 2008 to August
      2011. Factors associated with RCDC, the number of RCDC episodes, and the need for
      admission for RCDC were sought. RESULTS: A total of 739 patients (male, 47 %)
      were studied, of whom 527 (71 %) received inpatient treatment for their index
      episode of CDC. There was no difference (p = 0.53) between RCDC rates for
      inpatients (17.6 %) and outpatients (19.8 %). While severity score and albumin
      were associated with RCDC in our population, use of proton pump inhibitors (PPIs)
      correlated with decreased RCDC (p = 0.006) and decreased need for admission (p =
      0.005). The addition of vancomycin to metronidazole therapy did not lower RCDC
      rates (p = 0.52) or decrease the need for admission (p = 0.78). CONCLUSIONS:
      Hypoalbuminemia strongly correlated with higher recurrence rates, while PPI
      therapy actually reduced RCDC, representing previously underappreciated potential
      therapeutic targets for lowering CDC recurrence. The addition of vancomycin to
      metronidazole did not improve RCDC rates.

PMID- 23007287
TI  - Clinical and functional assessment of dysautonomia and its correlation in
      Alzheimer's disease.
AB  - The aims were to assess dysautonomia in Alzheimer's Disease (AD), clinically and
      electrophysiologically, using sympathetic skin response (SSR) test and R-R
      interval variation (RRIV) test and to analyze the relationship between symptoms
      of dysautonomia and SSR/RRIV results. A tota of 54 patients with AD and 37
      controls were evaluated using Autonomic Symptoms Questionnaire and SSR/RRIV test.
      Clinical dysautonomia was observed in 66% of patients (eg, orthostatic
      hypotension in 34.5%, constipation in 17.2%, urinary incontinence in 13.8%). The
      SSR test was abnormal in 26%, but the RRIV test was abnormal in 97.7% of cases;
      there was significant difference in RRIV test results between AD and controls (R
      mean 8.05% and 14.6%, respectively). In AD, clinical dysautonomia occurs at a
      various degree, and the abnormal SSR and RRIV test results were not always
      related to the presence of clinical dysautonomia; this observation points that
      the tests could be used as a useful tool in the assessment of subclinical
      dysautonomia.

PMID- 23007288
TI  - Promoting cognitive health: a web site review of health systems, public health
      departments, and senior centers.
AB  - Growing evidence suggests that healthy behaviors such as being physically active,
      having a heart healthy diet, and being socially involved may promote cognitive
      health. The United States has recently begun encouraging such behaviors for that
      purpose. To help evaluate the diffusion of this policy, we sought to measure a
      baseline of activity in this area. We examined Web sites of 156 large health care
      systems, the health departments of all 50 states and the 20 largest US cities,
      and 181 nationally accredited senior centers, to identify information, products,
      programs, or services recommended for cognitive health. Among health care
      systems, 40% promoted cognitive health: 24% recommended mental activity, 20%
      healthy diets, 20% physical activity, and 16% social involvement. Among health
      departments, 30% promoted cognitive health in the same ways. Among senior
      centers, 21% offered strategies, primarily mental activity. Results suggest
      emerging activity in this area and opportunities for continued development.

PMID- 23007289
TI  - Localization of decorin gene expression in normal human breast tissue and in
      benign and malignant tumors of the human breast.
AB  - The small extracellular matrix proteoglycan decorin which possesses a potent
      antitumor activity has been shown to be present in various amounts in the stroma
      of several tumors including those of the breast. Regarding decorin in breast
      malignancies the published data are conflicting, i.e., whether breast cancer
      cells express it or not. Here, we first compared decorin gene expression levels
      between healthy human breast tissue and selected types of human breast cancer
      using GeneSapiens databank. Next, we localized decorin mRNA in tissue specimen of
      normal human breast, intraductal breast papillomas and various histologic types
      of human breast cancer using in situ hybridization (ISH) with digoxigenin-labeled
      RNA probes for decorin. We also examined the effect of decorin transduction on
      the behavior of cultured human breast cancer MCF7 cells. Analysis of GeneSapiens
      databank revealed that in various human breast cancers decorin expression is
      significant. However, ISH results clearly demonstrated that human breast cancer
      cells independently of the type of the cancer do not express decorin mRNA. This
      was also true for papilloma-forming cells of the human breast. Indeed, decorin
      gene expression in healthy human breast tissue as well as in benign and malignant
      tumors of human breast was shown to take place solely in cells of the original
      stroma. Decorin transduction using decorin adenoviral vector in decorin-negative
      MCF7 cells resulted in a significant decrease in the proliferation of these cells
      and changed cell cohesion. Decorin-transduced MCF7 cells also exhibited increased
      apoptosis. In conclusion, our study shows that in human breast tissue only cells
      of the original stroma are capable of decorin gene expression. Our study also
      shows that transduction of decorin in decorin-negative human breast cancer cells
      markedly modulates the growth pattern of these cells.

PMID- 23007291
TI  - Combination therapy of infliximab and granulocyte/monocyte adsorption apheresis
      for refractory pustular psoriasis with psoriatic arthritis.

PMID- 23007290
TI  - Increased caveolae density and caveolin-1 expression accompany impaired NO
      mediated vasorelaxation in diet-induced obesity.
AB  - Diet-induced obesity induces changes in mechanisms that are essential for the
      regulation of normal artery function, and in particular the function of the
      vascular endothelium. Using a rodent model that reflects the characteristics of
      human dietary obesity, in the rat saphenous artery we have previously
      demonstrated that endothelium-dependent vasodilation shifts from an entirely
      nitric oxide (NO)-mediated mechanism to one involving upregulation of
      myoendothelial gap junctions and intermediate conductance calcium-activated
      potassium channel activity and expression. This study investigates the changes in
      NO-mediated mechanisms that accompany this shift. In saphenous arteries from
      controls fed a normal chow diet, acetylcholine-mediated endothelium-dependent
      vasodilation was blocked by NO synthase and soluble guanylyl cyclase inhibitors,
      but in equivalent arteries from obese animals sensitivity to these agents was
      reduced. The expression of endothelial NO synthase (eNOS) and caveolin-3 in rat
      saphenous arteries was unaffected by obesity, whilst that of caveolin-1 monomer
      and large oligomeric complexes of caveolins-1 and -2 were increased in membrane
      enriched samples. The density of caveolae was increased at the membrane and
      cytoplasm of endothelial and smooth muscle cells of saphenous arteries from obese
      rats. Dissociation of eNOS from caveolin-1, as a prerequisite for activation of
      the enzyme, may be compromised and thereby impair NO-mediated vasodilation in the
      saphenous artery from diet-induced obese rats. Such altered signaling mechanisms
      in obesity-related vascular disease represent significant potential targets for
      therapeutic intervention.

PMID- 23007292
TI  - Photophysical studies of CdTe quantum dots in the presence of a zinc cationic
      porphyrin.
AB  - The photophysical properties of 2.3 nm thioglycolic acid (TGA) coated CdTe
      quantum dots (QDs) prepared by a reflux method have been studied in the presence
      of cationic meso-tetrakis(4-N-methylpyridyl) zinc porphyrin (ZnTMPyP4). Addition
      of the CdTe QDs to the porphyrin in H(2)O results in a marked red-shift and
      hypochromism in the porphyrin absorption spectrum, indicative of a non-covalent
      binding interaction with the QD surface. Only low equivalents of the quantum dot
      were required for complete quenching of the porphyrin fluorescence revealing that
      one quantum dot may quench more than one porphyrin. Similarly addition of
      porphyrin to the quantum dot provided evidence for very efficient quenching of
      the CdTe photoluminescence, suggesting the formation of CdTe-porphyrin
      aggregates. Definitive evidence for such aggregates was gathered using small
      angle X-ray spectroscopy (SAXS). Ultrafast transient absorption data are
      consistent with very rapid photoinduced electron transfer (1.3 ps) and the
      resultant formation of a long-lived porphyrin species.

PMID- 23007293
TI  - Communication about adherence to long-term antipsychotic prescribing: an
      observational study of psychiatric practice.
AB  - PURPOSE: Partial or non-adherence is common in people taking antipsychotic
      medication. A good therapeutic alliance is thought by psychiatrists to encourage
      engagement with a service and improve adherence. This paper aims to examine how
      psychiatrists and patients communicate in outpatient consultations about partial
      or non-adherence to antipsychotic prescribing. METHODS: Ninety-two outpatient
      consultations involving patients prescribed antipsychotic medication and their
      psychiatrists were tape recorded. Parts of consultations where partial/non
      adherence to antipsychotic medication was discussed were analysed using
      conversation analysis. RESULTS: In 22 (24 %) consultations, partial/non-adherence
      was disclosed. Most commonly, it was volunteered without prompting and was more
      likely to be presented as a deliberate choice than omission by the patient.
      Psychiatrists responded to all but one disclosure, and patients delivered their
      reports in ways that minimised the prospect of this response being disciplinary.
      The most common outcome was a change in prescribing: a medication omission, swap
      or dosage reduction. CONCLUSIONS: Patients and psychiatrists work together to
      create a safe conversational environment in which to discuss this potentially
      difficult issue. Unlike previous studies of patient reports of psychotic symptoms
      and side effects of drowsiness being ignored, psychiatrists nearly always respond
      to disclosures of partial/non-adherence. Psychiatrists should apply the same
      listening skills to patients' disclosures of troubling side effects and psychotic
      symptoms.

PMID- 23007294
TI  - Lifetime traumatic experiences and their impact on PTSD: a general population
      study.
AB  - OBJECTIVE: Exploring the relationship of exposure to a traumatic event and the
      subsequent onset of posttraumatic stress disorder (PTSD) in the population.
      METHODS: Posttraumatic stress disorder was assessed using the Impact of Event
      Scale (IES), Posttraumatic Diagnostic Scale (PDS) and interview data. Logistic
      regression analyses with sex, age, marital status, educational level and
      traumatic event characteristics were performed. Prevalences were standardised to
      the sex and age distribution of the German population. RESULTS: A total of 41 %
      of the subjects reported exposure to a trauma, leading to full PTSD in 1.7 % and
      to partial PTSD in 8.8 % of the participants. Logistic regression revealed
      accidents (OR 2.5, 95 % CI 1.3-4.7), nonsexual assault by known assailants (4.5,
      2.1-9.8), combat/war experiences (5.9, 2.0-17.4), life-threatening illness (4.9,
      2.7-8.9) and interpersonal conflicts (15.5, 2.5-96.0) as risk factors for full
      PTSD; risk factors for partial PTSD were accidents (3.2, 2.4-4.3), sexual (4.6,
      2.2-9.6) or nonsexual (2.3, 1.4-3.8) assault by known assailants, life
      threatening illness (6.2, 4.6-8.3), death of relatives (5.0, 3.2-7.8) and
      interpersonal conflicts (22.0, 8.3-58.1). CONCLUSIONS: Of subjects exposed to
      traumatic events, only a minority developed PTSD indicating a relationship
      between characteristics of the exposure and the individual and the onset of PTSD.

PMID- 23007295
TI  - Description of long-term polypharmacy among schizophrenia outpatients.
AB  - OBJECTIVE: This large nationwide study describes the prevalence and predictors of
      long-term antipsychotic polypharmacy among patients with schizophrenia. METHODS:
      A register-based longitudinal study of all people in Finland, who had at least
      one hospitalization due to schizophrenia during the years 2000-2007 and who were
      alive on March 1, 2007. Entry to the cohort was defined from the first
      hospitalization for schizophrenia during the years 2000-2007, and the date of
      assessment of antipsychotic polypharmacy was March 1, 2007. We studied separately
      chronic (N = 8,037) and recent onset (N = 8,046) schizophrenia patients.
      Antipsychotic polypharmacy was defined as overlapping of two or more filled
      prescriptions of antipsychotics for over 60 days. RESULTS: In a total 16,083
      patients with schizophrenia the prevalence of antipsychotic polypharmacy was 46.2
      % (N = 7,436, mean age 47.5 years, male 55 %). The longer the duration of
      schizophrenia, the more common the antipsychotic polypharmacy. Long index
      hospitalization and being male significantly associated with antipsychotic
      polypharmacy among all schizophrenia patients. Especially, in chronic
      schizophrenia patients, the previous use of benzodiazepine like agents was
      associated with antipsychotic polypharmacy, but the use of antidepressants
      associated with less frequent antipsychotic polypharmacy. CONCLUSIONS:
      Antipsychotic polypharmacy was widely prevalent among patients with schizophrenia
      and it was associated with long hospitalizations and long duration of illness.
      Benzodiazepine use was associated with increased risk and antidepressant use with
      decreased risk of antipsychotic polypharmacy when the effect of other clinical
      and socioeconomic factors was adjusted. Research is needed of risks and benefits
      of antipsychotic polypharmacy and augmentation of antipsychotic with other
      psychoactive drugs.

PMID- 23007296
TI  - Mental illness and lost income among adult South Africans.
AB  - PURPOSE: Little is known regarding the links between mental disorder and lost
      income in low- and middle-income countries. The purpose of this study was to
      investigate the association between mental disorder and lost income in the first
      nationally representative psychiatric epidemiology survey in South Africa.
      METHODS: A probability sample of South African adults was administered the World
      Health Organization Composite International Diagnostic Interview schedule to
      assess the presence of mental disorders as defined in the Diagnostic and
      Statistical Manual of Mental Disorders, version IV. RESULTS: The presence of
      severe depression or anxiety disorders was associated with a significant
      reduction in earnings in the previous 12 months among both employed and
      unemployed South African adults (p = 0.0043). In simulations of costs to
      individuals, the mean estimated lost income associated with severe depression and
      anxiety disorders was $4,798 per adult per year, after adjustment for age,
      gender, substance abuse, education, marital status, and household size.
      Projections of total annual cost to South Africans living with these disorders in
      lost earnings, extrapolated from the sample, were $3.6 billion. These data
      indicate either that mental illness has a major economic impact, through the
      effect of disability and stigma on earnings, or that people in lower income
      groups are at increased risk of mental illness. The indirect costs of severe
      depression and anxiety disorders stand in stark contrast with the direct costs of
      treatment in South Africa, as illustrated by annual government spending on mental
      health services, amounting to an estimated $59 million for adults. CONCLUSIONS:
      The findings of this study support the economic argument for investing in mental
      health care as a means of mitigating indirect costs of mental illness.

PMID- 23007297
TI  - Adaptive functioning in children with epilepsy and learning problems.
AB  - In the study we describe adaptive functioning in children with epilepsy whose
      primary caregivers identified them as having learning problems. This was a cross
      sectional study of 50 children with epilepsy and learning problems. Caregivers
      supplied information regarding the child's adaptive functioning and behavior
      problems. Children rated their self-concept and completed a battery of
      neuropsychological tests. Mean estimated IQ (PPVT-III) in the participant
      children was 72.8 (SD = 18.3). On average, children scored 2 standard deviations
      below the norm on the Vineland Adaptive Behavior Scale-II and this was true even
      for children with epilepsy who had estimated IQ in the normal range. In
      conclusion, children with epilepsy and learning problems had relatively low
      adaptive functioning scores and substantial neuropsychological and mental health
      problems. In epilepsy, adaptive behavior screening can be very informative and
      guide further evaluation and intervention, even in those children whose IQ is in
      the normal range.

PMID- 23007298
TI  - The most cited works in Tourette syndrome.
AB  - The impact of scientific articles is proportional to the citations they have
      received. In this study, the most cited works ("citation classics") related to
      Tourette syndrome (TS) were identified as articles with more than 100 citations
      according to the Web of Science. We retrieved 89 highly cited articles, which
      were published in 26 journals: 54 clinical studies, 27 laboratory studies, 7
      reviews, and 1 classification article. Clinical studies consisted of
      phenomenologic evaluations of TS and comorbid behavioral problems (n = 22) and
      studies on pharmacotherapy (n = 16) and clinical genetics (n = 13), whereas
      laboratory studies covered basic genetics, cellular and molecular biology (n =
      11), and neurobiology (neuroimaging, neuropathology, and neurophysiology) (n =
      16). The majority (58%) of citation classics were published after 1990, when
      laboratory studies (especially neuroimaging, immunologic, and genetic studies)
      became widely cited. These articles are able to reach the highest numbers of
      citations in a short time span and suggest potential directions for future
      research.

PMID- 23007299
TI  - The declining use of the Hallervorden-Spatz eponym.

PMID- 23007300
TI  - A case of infantile de novo primary antiphospholipid syndrome revealed by a
      neonatal arterial ischemic stroke.
AB  - The few cases of antiphospholipid syndrome that have been reported in neonates
      are believed to have resulted from a transplacental transfer of antiphospholipid
      antibodies. Here we report on a boy with a neonatal stroke revealing a de novo
      primary antiphospholipid, the mother being free of antiphospholipid antibodies.
      Other thrombosis risk factors included primiparity, gestational diabetes,
      macrosomia, polyglobulia, and lipoprotein(a) >30 mg/dL. Anti-cardiolipin and anti
      beta(2)-glycoprotein I persisted more than 2 years. Under aspirin therapy, the
      child did not exhibit recurrence of thrombotic events or symptoms of autoimmunity
      after a follow-up of 3 years. Our case indicates that clinicians should consider
      a second retesting for anticardiolipin antibodies and anti-beta(2)-glycoprotein I
      antibodies, even when children and mother neonatal tests are negative.

PMID- 23007301
TI  - Prevalence of ADHD and epilepsy.

PMID- 23007302
TI  - Response to comments on: Prevalence epilepsy and attention-deficit hyperactivity
      disorder.

PMID- 23007303
TI  - In memoriam: David L. Rimoin (1936-2012).

PMID- 23007304
TI  - In memoriam: Donald W. Lewis, MD (1951-2012 ).

PMID- 23007305
TI  - In Memorium: Bhuwan Garg, MBBS (1944-2012).

PMID- 23007308
TI  - Worldwide strategy for implementation of paediatric endoscopy: Report of the
      FISPGHAN Working Group.

PMID- 23007309
TI  - Does the stereochemistry of methylated cuticular hydrocarbons contribute to mate
      recognition in the egg parasitoid wasp Ooencyrtus kuvanae?
AB  - Close-range sexual communication of the egg parasitoid wasp Ooencyrtus kuvanae
      (Hymenoptera: Encyrtidae) takes place on host gypsy moth, Lymantria dispar
      (Lepidoptera: Lymantriidae), egg masses. We tested the hypothesis that mate
      recognition in O. kuvanae is mediated, in part, by low-volatility cuticular
      hydrocarbon (CHC) pheromone components. Gas chromatographic and GC-mass
      spectrometric analyses of body surface extracts of male and female wasps revealed
      no sex-specific components, but 5-methylheptacosane (5-me-27Hy) and 5,17
      dimethylheptacosane (5,17-dime-27Hy) were consistently more abundant in extracts
      of males. The ratio of 5-me-27Hy and 5,17-dime-27Hy was similar in extracts of
      males and females, and quantitative differences alone seemed insufficient to
      impart sex-specific CHC profiles. Therefore, we further hypothesized that the
      absolute configuration of 5-me-27Hy and 5,17-dime-27Hy contributes to mate
      recognition or attraction. As the stereoisomers of 5-me-27Hy and 5,17-dime-27Hy
      cannot currently be separated chromatographically, we could not determine the
      stereochemistry of the insect-produced components. Instead, we synthesized all
      stereoisomers and bioassayed synthetic blends in laboratory experiments. Of eight
      2-component blends, each blend containing one of the two enantiomers of 5-me-27Hy
      and one of the four stereoisomers of 5,17-dime-27Hy, the blend of (5S)
      methylheptacosane and (5R,17S)-dimethylheptacosane attracted males, whereas the
      blend of (5R)-methylheptacosane and (5R,17R)-dimethylheptacosane repelled males.
      Apparent recognition of both pheromone components and pheromone antagonists by
      males supports the hypothesis that the stereochemistry of 5-me-27Hy and 5,17-dime
      27Hy, and possibly other methylated CHCs, may differ between male and female O.
      kuvanae, and that these differences may serve in mate attraction and recognition.

PMID- 23007310
TI  - Nyhus-Wantz Lectureship: EHS/AHS Joint Hernia Congress-2012.
AB  - When given the honor to deliver the Nyhus-Wantz Lecture at the 5th Annual AHS/EHS
      International Hernia Congress, the word that came to mind immediately was
      collegiality. The dictionary tells us collegiality is the cooperative interaction
      among colleagues. I believe that both Doctors Nyhus and Wantz epitomized this
      cooperation. Both surgeons were critical in the exchange of ideas between Europe
      and The Americas regarding herniology that were critical to our past and laid the
      foundation for our future. In addition, both Doctors Nyhus and Wantz and their
      work have been extremely important in my development as a hernia surgeon. During
      the lecture, I will try to touch on these concepts to honor those that have made
      us what we are today.

PMID- 23007311
TI  - VEGF genetic polymorphisms affect the responsiveness to sildenafil in clinical
      and postoperative erectile dysfunction.
AB  - Vascular endothelial growth factor (VEGF) is a cytokine involved in angiogenesis
      and is closely related to the nitric oxide-cyclic guanosine monophosphate
      pathway, a target for sildenafil. We investigated for the first time whether
      three clinically relevant polymorphisms in the VEGF gene are associated with
      altered responsiveness to sildenafil treatment in postoperative erectile
      dysfunction (PED) and clinical erectile dysfunction (CED). We determined VEGF
      genotypes for three polymorphisms in VEGF promoter: -2578C>A (rs699947), -1154G>A
      (rs1570360) and -634G>C (rs2010963) in 126 patients with erectile dysfunction
      (ED; 66 patients with PED and 60 patients with CED). The patients were classified
      as good or poor responders to sildenafil (GR and PR groups, respectively)
      according to their responses with basis on the changes in five-item version of
      the International Index for Erectile Function (5-IIEF). We found an association
      of the -1154AA genotype with PR in both PED and CED patients (P<0.05), whereas
      the -2578AA and the -2578CA genotypes were associated with PR only in the CED
      group (P<0.05). The AAG haplotype was more common in PR than in GR patients (38%
      versus 20%, respectively; P=0.032) in the CED group, thus increasing the risk for
      a worse response to sildenafil (odds ratio, OR=2.33, 95% confidence interval,
      CI=1.07-5.09). However, this finding does not resist to Bonferroni's correction
      (P>0.0125). Our results indicate that VEGF polymorphisms affect the
      responsiveness of PED and CED patients to sildenafil. These findings may help to
      improve the therapy of patients with ED. 

PMID- 23007312
TI  - Feasibility of intraoperative radiation therapy for early breast cancer in Japan:
      a single-center pilot study and literature review.
AB  - BACKGROUND: Intraoperative radiation therapy (IORT) is under evaluation in breast
      conserving surgery because the feasibility of the IORT procedure including
      transportation of the patient under general anesthesia is not well established.
      Thus, this prospective single-center study aimed to test the feasibility of IORT
      at a single dose of 21 Gy in Japanese breast cancer patients. METHODS: The
      primary endpoint was early toxicity; the secondary endpoint was late toxicity.
      Patients with histologically or cytologically proven primary early breast cancer
      were eligible. Inclusion criteria were as follows: (1) T < 2.5 cm; (2) desire for
      breast-conserving surgery; (3) age >50 years; (4) surgical margin >1 cm; (5)
      intraoperative pathologically free margins; and (6) sentinel node negative.
      Exclusion criteria were (1) contraindications to radiation therapy; (2) past
      radiation therapy for the same breast or chest; (3) extensive intraductal
      component; and (4) a tumor located in the axillary tail of the breast. All
      patients gave written informed consent. Partial resection was performed with at
      least a margin of 1 cm around the tumor. The patient was transported from the
      surgical suite to the radiation room. Radiation (Clinac((r)) 21EX, Varian Medical
      Systems, Inc.) at 21 Gy was delivered directly to the mammary gland. Toxicity was
      evaluated with the Common Terminology Criteria for Adverse Events V4.0. RESULTS:
      Five patients were enrolled in this pilot study and received 21 Gy. Follow-up
      ranged from 7.8 to 11.0 months (median 10.2). Intraoperative transportation to
      the radiation room during the surgical procedure under general anesthesia was
      performed safely in all patients. Treatment-related toxicities within 3 months
      were deep connective tissue fibrosis (grade 1, n = 3) and pain (grade 1, n = 3).
      There was no case of wound infection, wound dehiscence, or soft tissue necrosis.
      Overall, there was no severe adverse event. CONCLUSIONS: The procedure was
      tolerated very well in this first group of Japanese female patients treated with
      IORT, as was the case with European women. A longer follow-up is needed for the
      evaluation of any potential late side effects or recurrences. A phase II study is
      now being conducted for the next group of patients (UMIN000003578).

PMID- 23007313
TI  - Ethical issues of genetic susceptibility testing for occupational diseases:
      opinions of trainees in a high-risk job.
AB  - PURPOSE: Genetic research has opened up possibilities for identification of
      persons with an increased susceptibility for occupational disease. However,
      regulations considering the ethical issues that are inevitably associated with
      the use of genetic tests for susceptibility for occupational diseases are scarce.
      We investigated whether opinions of an intended stakeholder group, that is,
      student nurses, are sufficiently addressed by existing recommendations. METHODS:
      Attitudes and opinions of Dutch student nurses toward a genetic test for
      susceptibility to occupational contact eczema were studied in a qualitative setup
      using focus groups, interviews and electronic questionnaires. The results were
      compared with guidelines and recommendations extracted from the literature.
      RESULTS: Sixty-nine percent of the student nurses said they would partake in a
      genetic test for susceptibility to occupational contact eczema when available.
      Concerns were expressed regarding the difficulty of interpreting test results,
      the utility of the test result in practice and the necessity of genetic tests for
      non-severe diseases. For the issue of privacy and confidentiality, the students
      expressed few worries and much confidence. The existing guidelines largely
      covered the students' opinions. Still, the data emphasized the need for good
      individual risk communication both before and after testing, taking into account
      that the test concerns susceptibility. CONCLUSIONS: Comparing the students'
      statements with the issues addressed by the guidelines, we conclude that the
      guidelines should pay more attention to risk communication and practical advice
      accompanying the test results.

PMID- 23007315
TI  - National trends in visit rates and antibiotic prescribing for adults with acute
      sinusitis.

PMID- 23007314
TI  - Respiratory health and breath condensate acidity in sawmill workers.
AB  - PURPOSE: The aim of the study was to evaluate exhaled breath condensate acidity
      (EBC pH) as a biomarker of airway response to occupational respiratory hazards
      present in sawmill. METHODS: Sixty-one sawmill workers in total (26 from Sawmill
      1 and 35 from Sawmill 2) provided EBC samples at the beginning and at the end of
      the working week. Respiratory symptoms, lung function, bronchodilator test and
      atopy status were assessed. Occupational environment was checked for the levels
      of respiratory hazards. RESULTS: Airborne dust concentrations were below
      threshold limit value. Endotoxin in Sawmill 1 and Sawmill 2, and moulds in
      Sawmill 1 were at the levels able to induce inflammatory response in the airways.
      Mould levels were 2.5 times higher in Sawmill 1 than in Sawmill 2. Compared to
      Sawmill 2 workers, lower spirometry values, higher prevalence of dry cough and
      positive bronchodilator test were found in Sawmill 1 workers. Monday EBC pH
      values did not differ between sawmills, but declined after one working week in
      Sawmill 1 workers (from 7.88 to 7.49, P = 0.012) and not in Sawmill 2 workers.
      Similar results were obtained when only respiratory healthy non-smokers were
      analysed. Monday-to-Friday change of other respiratory parameters was not
      observed. CONCLUSION: The results suggest EBC pH as a biomarker of acute
      respiratory effects related to occupational exposure to respiratory hazards in
      sawmills, presumably increased mould levels. The effect was present even at
      subclinical level, namely in respiratory healthy subjects. The long-term health
      implications remain unclear and should be evaluated in a follow-up study.

PMID- 23007316
TI  - Preclinical evaluation of the novel 7-substituted camptothecin Namitecan (ST1968)
      in paediatric tumour models.
AB  - PURPOSE: The present study aimed to evaluate the new water soluble camptothecin
      analogue Namitecan (ST1968) in preclinical paediatric tumour models of the
      nervous system comprehensive of neuroblastoma, primitive neuroectodermal
      tumours/PNET and medulloblastoma where the drug was compared to Irinotecan.
      METHODS: Cellular sensitivity to the drug was assessed by MTT and clonogenic
      assays. Propidium iodide staining was used for cell cycle perturbation studies.
      The genotoxic effects were quantified by Comet assay, whereas apoptosis was
      assessed by PARP cleavage and sub-G1 accumulation. Tumour response was
      investigated in xenograft models in nude mice. RESULTS: The cellular response to
      Namitecan was heterogeneous with IC(50) (2 h) ranging between 0.14 and 13.26 MUM,
      whereas SN38 (the active metabolite of Irinotecan) appeared more effective
      (IC(50): 0.03-11.7 MUM). Interestingly, prolonged drug incubation times up to 72
      h enhanced Namitecan cytotoxicity, with similar colony inhibition curves between
      the two analogues (IC(50), nM-SN38: 0.9 +/- 0.2; Namitecan: 0.7 +/- 0.4). DNA
      damage, accumulation in late-S/G2 phases and induction of apoptosis appeared
      important players of Namitecan cytotoxicity in our models. In vivo, Namitecan was
      superior to Irinotecan in three out of five xenograft models, with reversible
      weight loss (10 %). In the sensitive SK-N-AS xenograft, Namitecan showed a high
      retention in tumours consistently with: high antitumour response, rapid drug
      mediated DNA damage (60 % mean TailDNA after 1 h from drug inoculation),
      persistent cell cycle perturbation (60-40 % G2 accumulation after 48-72 h,
      respectively) and apoptosis. Studies with Namitecan and platinum agents in this
      model showed a significant enhancement of antitumour activity of the drugs
      combination versus single agents. CONCLUSIONS: Our preclinical data strongly
      support the interest of further investigations on the well-tolerated Namitecan
      either as a single agent or in combination in paediatric oncology.

PMID- 23007318
TI  - Metabolism: no role for osteocalcin in glucose metabolism--challenging a
      paradigm?

PMID- 23007317
TI  - Thyroid disorders in pregnancy.
AB  - The thyroid gland is substantially challenged during pregnancy. Total T(3) and
      T(4) levels increase by 50% during pregnancy owing to a 50% increase in thyroxine
      binding globulin levels. Serum TSH levels decrease in the first trimester and
      increase in the second and third trimesters; however, not to prepregnancy levels.
      Hypothyroidism is present in up to 3% of all pregnant women. Subclinical
      hypothyroidism during pregnancy is associated with an increased rate of
      miscarriage and preterm delivery, and a decrease in the IQ of the child. Overt
      hyperthyroidism is present in less than 1% of pregnant women but is linked to
      increased rates of miscarriage, preterm delivery and maternal congestive heart
      failure. In women who are euthyroid, thyroid autoantibodies are associated with
      an increased risk of spontaneous miscarriage and preterm delivery. Postpartum
      thyroiditis occurs in 5.4% of all women following pregnancy; moreover, 50% of
      women who are euthyroid in the first trimester of pregnancy but test positive for
      thyroid autoantibodies will develop postpartum thyroiditis. The need for the
      essential nutrient iodine increases during pregnancy and in women who are
      breastfeeding, and the effect of treatment of mild iodine deficiency on maternal
      and fetal outcomes is consequently being evaluated in a prospective study. The
      debate regarding the pros and cons of universal screening for thyroid disease
      during pregnancy is ongoing.

PMID- 23007319
TI  - Maternal adiposity--a determinant of perinatal and offspring outcomes?
AB  - Experimental and animal data suggest that maternal obesity during pregnancy
      adversely affects offspring health in the short-term and the long-term. Whether
      these effects occur in humans and influence population health is less clear. This
      Review explores evidence from intervention studies and observational studies that
      have used designs (such as family-based comparisons and Mendelian randomization)
      that might help improve understanding of the causal effects of maternal obesity
      in humans. Collectively, human studies provide evidence that maternal overweight
      and obesity is causally related to pregnancy complications, increased offspring
      weight and adiposity at birth, and the difficulties associated with delivery of
      large-for-gestational-age infants. The underlying mechanisms for these effects
      probably involve maternal and fetal dysregulation of glucose, insulin, lipid and
      amino acid metabolism. Some evidence exists that extreme maternal obesity (BMI
      >=40 kg/m(2)) is causally related to a long-term increase in offspring adiposity,
      but further exploration of this relationship is needed. High gestational weight
      gain may result in a long-term increase in offspring adiposity if women are
      already overweight or have obesity at the start of pregnancy. To date, little
      high-quality human evidence exists that any of these effects are mediated by
      epigenetic mechanisms, but approaches to appropriately test this possibility are
      being developed.

PMID- 23007320
TI  - Nutrition: ejecting trans fat from New York City restaurants.

PMID- 23007321
TI  - Reproductive endocrinology: menstrual cycle lengths--what can they tell us?

PMID- 23007322
TI  - A portable and autonomous multichannel fluorescence detector for on-line and in
      situ explosive detection in aqueous phase.
AB  - A multichannel fluorescence detector used to detect nitroaromatic explosives in
      aqueous phase has been developed, which is composed of a five-channel sample
      sensor unit, a measurement and control unit, a microcontroller, and a
      communication unit. The characteristics of the detector as developed are mainly
      embedded in the sensor unit, and each sensor consists of a fluorescent sensing
      film, a light emitting diode (LED), a multi-pixel photon counter (MPPC), and an
      optical module with special bandpass optical filters. Due to the high sensitivity
      of the sensing film, the small size and low cost of LED and MPPC, the developed
      detector not only has a better detecting performance and small size, but also has
      a very low cost - it is an alternative to the device made with an expensive high
      power lamp and photomultiplier tube. The wavelengths of the five sensors covered
      extend from the upper UV through the visible spectrum, 370-640 nm, and thereby it
      possesses the potential to detect a variety of explosives and other hazardous
      materials in aqueous phase. An additional function of the detector is its ability
      to function via a wireless network, by which the data recorded by the detector
      can be sent to the host computer, and at the same time the instructions can be
      sent to the detector from the host computer. By means of the powerful computing
      ability of the host computer, and utilizing the classical principal component
      analysis (PCA) algorithm, effective classification of the analytes is achieved.
      Furthermore, the detector has been tested and evaluated using NB, PA, TNT and DNT
      as the analytes, and toluene, benzene, methanol and ethanol as interferent
      compounds (concentration various from 10 and 60 MUM). It has been shown that the
      detector can detect the four nitroaromatics with high sensitivity and
      selectivity.

PMID- 23007323
TI  - Early glottic carcinoma treated by radiotherapy: defining a population for
      surgical salvage.
AB  - OBJECTIVES/HYPOTHESIS: Not all patients with early Glottis squamous cell
      carcinoma will be cured by radiotherapy. This is an audit of a single center's
      experience with those patients who fail by this approach. STUDY DESIGN: This
      retrospective study was approved by the IRB (Institutional Review Board);
      eligibility criterion was patients treated between 1967 and December 2006, T(IS),
      T(1), T(2) N(0) SCC glottic carcinoma, with analysis occurring in 2009, and with
      a minimum follow-up of 2 years. METHODS: The eligibility criteria for this ethics
      approved study was that all patients started a course of radiotherapy for early
      glottic laryngeal SCC. Data included in the Larynx Cancer database includes
      information from the Radiation Oncology Department notes, referral letters, and
      follow-up information. This is categorized into patient, disease, and treatment
      factors. RESULTS: Of 522 patients who commenced radiotherapy, local failure
      occurred in 105 patients; a salvage procedure was performed in 89, with surgery
      only in 83. For these 89 patients, the ultimate local control was 67%, with a
      larynx preservation procedure in 34%. Nodal failure occurred in 20 of the 522
      patients (4%). There was a much higher failure rate in patients unfit for surgery
      (10/26-38%). Laryngectomy was the main salvage procedure in 55 patients.
      CONCLUSIONS: Early recognition of local failure following radiotherapy for early
      glottic carcinoma may avoid laryngectomy as a salvage procedure.

PMID- 23007324
TI  - Efficacy and tolerability of a cream containing AR-GG27(r) (sorbityl furfural
      palmitate) in the treatment of mild/moderate childhood atopic dermatitis
      associated with pityriasis alba. A double-blind, placebo-controlled clinical
      trial.
AB  - AIM: Pityriasis alba (PA) is a skin disorder characterized by finely scaly,
      hypopigmented patches, typical of childhood, that also represents an atopic
      dermatitis (AD) minor sign according to Hanifin and Rajka criteria. It may be
      isolated or associated with AD representing, sometimes an atypical manifestation
      of AD during the long-term follow-up of the disease. Aim of the study was to
      evaluate of the efficacy and tolerability of AR-GG27(r) (sorbityl furfural
      palmitate) cream in the treatment of childhood mild or moderate AD associated
      with PA. METHODS: The trial is a single center, double-blind, randomized, placebo
      controlled study. The study included patients of both sexes, aged between two
      months and 15 years, suffering from mild and moderate AD always associated with
      PA. Xerosis was present in all patients. The treatment with topical steroids or
      topical calcineurin inhibitors (TIMs) had to be suspended for at least 15 days.
      Any systemic therapy and phototherapy or sun exposure were withdrawn at least 30
      days before. Emollients were stopped at least seven days before. During the
      trial, no other local or systemic treatments were allowed, as well as sun
      exposure. Patients affected by AD with viral, bacterial or fungal overinfection
      or patients with diabetes mellitus, severe systemic diseases or intolerance to
      one or more components of the product were excluded. The primary endpoint was the
      evaluation of the average change in the Investigator Global Assessment (IGA)
      after 15 and 30 days of treatment. The second endpoint was the evaluation of
      severity of three different clinical signs: erythema, excoriation desquamation,
      using a subjective five-point scale. Changes in pruritus severity was also
      considered during the entire period of treatment, through the use of a Visual
      Analogue Scale (VAS). A P<0.05, two tailed was considered as statistically
      significant. RESULTS: After 15 and 30 days there was a statistically significant
      difference in the group treated with AR-GG27(r), compared to the placebo
      (respectively, P=0.0007 and P=0.005). After 15 days of treatment, itching was
      clearly reduced in AR-GG27(r) treated group compared with the placebo, both in
      the study population (P=0.01) and in patients where the symptom was present from
      the beginning (P=0.05). CONCLUSION: AR-GG27(r) showed a beneficial action
      associated with high compliance and tolerability in dermatological skin
      conditions characterized by inflammation and tissue oxidative stress in children,
      as PA with mild and moderate AD.

PMID- 23007325
TI  - CD151 promotes cancer cell metastasis via integrins alpha3beta1 and alpha6beta1
      in vitro.
AB  - CD151 is a member of the tetraspanin family that is implicated as a promoter of
      the tumor metastasis of malignant cells. Tetraspanins form membrane complexes
      with integrins. In the present study, we constructed a CD151-AAA mutant to assess
      the roles of Rac, cdc42 and phospho-Rac/cdc42 (P-Rac/cdc42) and the effects of
      CD151-integrin complexes on the proliferation, migration and invasion of HepG2
      cells. The pAAV-CD151 and pAAV-CD151-AAA mutant plasmids were constructed and
      used to transiently transfect HepG2 cells using the Qiagen Attractene
      transfection reagent. Following transfection, the expression of CD151 was
      determined by western blotting. A cell proliferation assay was performed using
      the cell counting kit-8 (CCK-8) method, cell migration was assessed by a cell
      wound-healing assay and cell invasion was evaluated in microchemotaxis chambers
      using FBS as the chemotactic stimulus. The potential involvement of various
      signaling pathways was explored using relevant antibodies. The association
      between CD151 and integrins was evaluated by immunoblotting analysis. We found
      that CD151 promoted cell proliferation, migration and chemotaxis and increased P
      Rac/cdc42 activity. The CD151-AAA mutant had reduced cellular proliferation,
      migration and invasion compared with the CD151 mutant. Moreover, the CD151-AAA
      mutant abrogated the association between CD151 and integrins. These data suggest
      that CD151 forms complexes by interacting with integrins, particularly
      alpha3beta1 and alpha6beta1, and thereby affects the functioning of the HepG2
      cells. The mechanism is possibly related to the Rac, cdc42 and P-Rac/cdc42
      signaling pathways.

PMID- 23007326
TI  - Splenic marginal zone lymphoma in a HIV-1 infected patient: evidence favouring a
      pathogenetic role of HIV-1 itself in the lymphomagenesis.
AB  - A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency
      virus (HIV)-1 infected patient is described. As an association between SMZL and
      viral infections has been reported, the presence of the hepatitis C virus and HIV
      1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic
      B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.

PMID- 23007327
TI  - [Measures for allergic disease and medical network in Japan].

PMID- 23007328
TI  - [One point message of Japanese Pediatric Guideline for Food Allergy 2012].

PMID- 23007329
TI  - [Guidelines for the management of urticaria -second line treatment for idiopathic
      urticaria].

PMID- 23007330
TI  - [Three faces of allergen].

PMID- 23007331
TI  - [Drug therapy and pharmacogenetics].

PMID- 23007332
TI  - [Therapeutic approach to mite-induced intractable dermatitis using novel
      immunomodulator FTY720 (fingolimod) in combination with betamethasone ointment in
      NC/Nga mice].
AB  - BACKGROUND: The increasing incidence and prevalence of atopic dermatitis (AD)
      have led to a requirement for new means to treat the disease. We investigated the
      therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and
      in combination with betamethasone valerate ointment, in the NC/Nga mouse model of
      mite-induced intractable dermatitis. METHODS: Female NC/Nga mice in which
      dermatitis had been induced with Dermatophagoides farinae were divided into six
      groups: 1) a betamethasone group (betamethasone ointment, six times a week), 2)
      an FTY720 group (FTY720, orally, three times a week), 3) an FTY720 plus
      betamethasone ointment group, 4) an ointment base group (ointment base, six times
      a week), 5) an FTY720 plus ointment base group and 6) a placebo group (vehicle
      alone). The therapeutic efficacy was evaluated in terms of the severity of
      dermatitis and histochemical observations after two weeks of treatment. RESULTS:
      Betamethasone treatment had little effect, confirming that the dermatitis was
      intractable. In the FTY720 plus betamethasone ointment group, the dermatitis was
      significantly improved as compared with the betamethasone ointment and placebo
      groups. This combination therapy also suppressed epidermal hypertrophy and
      accumulation of mast cells and CD3+T-cells in dermis, all of which were observed
      in mice in which the dermatitis had become established. CONCLUSION: Our results
      strongly suggest that the combination of FTY720 plus betamethasone ointment is a
      promising candidate for treatment of intractable human AD.

PMID- 23007333
TI  - [Persistence rate for clinic visit in children with asthma after initiating
      controller therapy].
AB  - OBJECT: To investigate the actual condition of the persistence rate for clinic
      visit in children with asthma requiring controller medication. METHODS: Seventy
      three asthma children (0 to 15 years of age) who initiated controller medication
      were enrolled this study. Patients and their parents were educated about this
      disease (mechanism of asthma, airway inflammation, and necessity of asthma
      medication) and instructed to visit clinics regularly every 30 days. We
      prospectively monitored visit rate of the patients for 180 days. RESULTS: Mean
      persistence rate for clinic visit of all patients was gradually decreased, 90.4%
      on the 30 day, 82.2% on the 60 day, 78.1% on the 90 day, 67.1% on the 120 day and
      38.4% on the 180 day, respectively. The persistence rate on the 180 day of 2 to 5
      years old patients was significantly lower than that of < 2 years old patients
      and the rate on the 60 days or more after in 6 to 15 years old patients was lower
      than that of < 2 years old patients. It was also significantly lower in patients
      with moderate and severe persistent asthma than in mild persistent patients.
      CONCLUSION: Despite of the investigation in the setting of asthma specialty
      clinic, the persistence rate for clinic visit was decreased with time, especially
      in 6 to 15 years old or moderate to severe asthmatic patients. In order to
      improve the situation, it is necessary to analyze the cause of poor adherence and
      make a concrete action plan.

PMID- 23007334
TI  - [Three cases with high TARC levels of gastrointestinal food allergies in neonates
      and infants].
AB  - We measured serum TARC (Thymus and activation-regulated chemokine, CCL-17) levels
      in three patients of gastrointestinal food allergies in neonates and infants.
      Patient 1: 14-day-old girl. The chief complaints were poor feeding and weight
      loss. She tested peripheral eosinophilia (5820 /MUL), high serum TARC levels
      (4730 pg/mL) and positive milk-specific IgE (1.53 UA/mL) at the time of onset.
      After change from cow' milk formula to hydrolyzed infant formulas and breast milk
      ahead of dairy products intake, the symptoms resolved. One month and a half
      later, she re-tested negative milk-specific IgE and normal serum TARC levels (198
      pg/mL). Patient 2: 3-month-old girl. The chief complaint was vomiting after
      intake of cow' milk formula. She tested negative milk-specific IgE and very high
      serum TARC levels (25200 pg/mL) at the time of onset. After changing to
      hydrolyzed infant formulas and breast milk ahead of dairy products intake, the
      symptom resolved. Three months later, she re-tested positive milk-specific IgE
      (0.42 UA/mL) and normal serum TARC levels (1250 pg/mL). Patient 3: 21-day-old
      boy. The chief complaint was vomiting after intake of cow' milk formula. He
      tested peripheral eosinophilia (2923 /MUL), very high serum TARC levels (49100
      pg/mL) and positive milk-specific IgE (0.47 UA/mL) at the time of onset. After
      changing to hydrolyzed infant formulas and breast milk ahead of dairy products
      intake, the symptom resolved. Two weeks later, he re-tested negative milk
      specific IgE and serum TARC levels (2210 pg/mL). Serum TARC may be related to the
      part of gastrointestinal food allergies in neonates and infants.

PMID- 23007336
TI  - Alexithymia, negative emotions, and sexual behavior in heterosexual university
      students from Italy.
AB  - Alexithymia is a construct which denotes thought characterized by pragmatic
      content, an inability to recognize and verbally express emotion, a difficulty in
      distinguishing between feelings and bodily sensations, and a limitation in
      fantasy life. Research has revealed a role for alexithymia in different kinds of
      sexual dysfunctions; it was also associated with reduced frequency of penile
      vaginal intercourse but not with sexual behaviors-like masturbation-which do not
      include an emotional interaction in normal individuals. The aim of this research
      was to further investigate the association between alexithymia scores and sexual
      behavior in a sample of normal individuals, taking into account the role of
      gender differences and the possible effect of negative emotions (depression,
      anxiety, and anger). Participants were 300 university students (142 men and 158
      women); sexual behavior was measured by the Sex and the Average Woman (or Man)
      Scale while alexithymia was measured with the Toronto Alexithymia Scale. The
      findings of the study showed that higher alexithymia scores were associated with
      lower levels of sexual satisfaction and higher levels of sexual detachment for
      females, and with sexual shyness and sexual nervousness for both genders. Results
      also suggested that the correlations between alexithymia scores and sexual
      behavior are partially influenced by the effect of negative emotions. Overall, it
      seems that the same detachment which denotes the alexithymic interpersonal style
      also characterizes sexual behavior.

PMID- 23007337
TI  - Construction and characterization of a eukaryotic expression vector for small
      interfering RNA targeting the NEDD9 gene.
AB  - The aim of this study was to construct a eukaryotic expression vector for a small
      interfering RNA (siRNA) targeting the neural precursor cell expressed,
      developmentally downregulated 9 (NEDD9) gene, and to investigate the effects of
      RNA interference (RNAi) on NEDD9 expression in human lung adenocarcinoma A549
      cells. We used the siRNA design and analysis software to determine the target
      oligonucleotides according to the sequence of NEDD9 mRNA available in GenBank.
      Four siRNA sequences were obtained, and the corresponding cDNAs were synthesized
      and inserted into the pRNAT-CMV3.2 plasmid to construct the recombinant plasmids.
      These were transformed into the E. coli strain DH5alpha. The plasmids, after
      identification by PCR and DNA sequencing, were transfected into the A549 cell
      line via the liposome method. NEDD9 mRNA and protein in the cells were determined
      by fluorescence quantitative RT-PCR (FQ-PCR) and western blotting, respectively.
      The pRNAT-CMV3.2-transfected plasmid was used as a control. Four recombinant
      plasmids were identified by PCR and sequence analysis, which contained the
      correct insertion of the designed sequences in the plasmids. FQ-PCR and western
      blotting showed substantially decreased mRNA and protein expression of the NEDD9
      gene in the transfected cells, compared with the control group. In conclusion,
      the recombinant plasmids expressing the siRNA targeting the NEDD9 gene were
      successfully constructed, and the siRNA expression vectors inhibited the
      expression of NEDD9 in A549 cells.

PMID- 23007338
TI  - Human parathyroid hormone increases the mRNA expression of the IGF system and
      hematopoietic growth factors in osteoblasts, but does not influence expression in
      mesenchymal stem cells.
AB  - Osteoblasts, which are derived from pluripotent mesenchymal stem cells (MSCs),
      play an important role in hematopoiesis. Human parathyroid hormone (hPTH) induces
      osteoblasts to produce many factors that are essential to hematopoietic stem
      cells. However, little is known about the impact of hPTH on MSCs to enhance
      hematopoiesis. We determined the optimal dose of hPTH that was necessary in vitro
      for increased osteoblast function. In addition, we compared MSC and osteoblast
      function to explore the role of hPTH in hematopoiesis. The mRNA expression levels
      of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony
      stimulating factor (GM-CSF), interleukin 6, stromal cell-derived factor 1,
      insulin-like growth factor 1 (IGF-1), IGF-2, insulin-like growth factor-binding
      protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 were comparable in osteoblasts and
      human cord blood-derived MSCs. However, G-CSF, GM-CSF, IGF-2, IGFBP-1, IGFBP-2,
      and IGFBP-3 expression levels in osteoblasts were markedly increased after
      treatment with 50 or 100 nM of hPTH. In conclusion, hPTH does not affect the
      ability of MSCs to differentiate into osteoblasts. In addition, hPTH may enhance
      hematopoiesis by activating the IGF system (IGF-2, IGFBP-1, IGFBP-2, and IGFBP-3)
      and hematopoietic growth factors (G-CSF and GM-CSF) in osteoblasts, but not in
      MSCs.

PMID- 23007339
TI  - Gemcitabine, docetaxel, and bevacizumab in relapsed and refractory pediatric
      sarcomas.
AB  - BACKGROUND: The outcome for patients with relapsed and refractory pediatric
      sarcomas remains dismal. Novel agents are needed to improve overall survival in
      these patients. OBSERVATIONS: We present 3 patients with relapsed/refractory
      sarcomas treated with gemcitabine, docetaxel, and bevacizumab in 3-week cycles.
      The combination was well tolerated with minimal toxicity. Two patients had a
      partial response and the third patient had stable disease for >6 months.
      CONCLUSIONS: These results are limited by small patient numbers but this strategy
      should be evaluated in prospective clinical trials.

PMID- 23007340
TI  - Late-onset blueberry muffin lesions following recombinant erythropoietin
      administration in a premature infant.
AB  - Recombinant erythropoietin is being used in premature population for anemia of
      prematurity. It is considered very safe in this population, although risks are
      still being evaluated. We report the first case of dermal erythropoiesis as a
      side effect of recombinant erythropoietin in an extremely prematurely born infant
      presenting with late-onset blueberry muffin lesions.

PMID- 23007341
TI  - Report of a young girl with MYH9 mutation and review of the literature.
AB  - MYH9 mutations cause the inherited macro-thrombocytopenic syndromes of May
      Hegglin anomaly, Fechtner syndrome, Sebastian syndrome, and Epstein syndrome,
      collectively referred to as MYH9-related disease. We present the case of a girl
      with MYH9-related disease whose diagnosis was facilitated by platelet electron
      microscopy and MYH9 sequencing. We discuss our patient's clinical presentation,
      now with 12 years of follow-up. We also discuss management and her possible
      prognosis given her specific MYH9 mutation.

PMID- 23007342
TI  - Total skin electron beam radiation in a pediatric patient with leukemia cutis:  a
      case report.
AB  - Leukemia cutis, a form of extramedullary leukemia involving the skin, is a poor
      prognostic marker and indicator of imminent hematologic relapse and
      chemotherapeutic resistance in leukemia patients. Although total skin electron
      beam radiotherapy is commonly recommended for patients with leukemia cutis, its
      role and effectiveness remains unclear. Here we describe a 19-month-old infant
      with acute myelogenous leukemia first diagnosed at 15 months of age. It relapsed
      in her skin at 18 months of age, associated with raised hyperpigmented lesions on
      her chest and scalp. Radiation treatment to the total skin surface with radiation
      therapy resulted in relief of her symptoms before relapse in the bone marrow.

PMID- 23007343
TI  - Pulmonary metastasis in neuroblastoma at initial diagnosis.

PMID- 23007345
TI  - Metastatic renal cell carcinoma in children and adolescents:  a 30-year
      unsuccessful story.
AB  - BACKGROUND: Because of the rare occurrence of renal cell carcinoma (RCC) among
      children very little is known about this malignancy in pediatric age. We aimed
      adding knowledge on the clinical characteristics and outcome of metastatic (m)
      RCC in children and adolescents. PATIENTS AND METHODS: The series included 14
      stage 4 RCC patients with a median age at diagnosis of 155.5 months, observed at
      the Italian Pediatric Hematology and Oncology Association (AIEOP) centers from
      January 1973 to November 2010. We were able to reevaluate histopatology of 11 out
      of the 14 patients and perform immunostaining for TFE3 in 9 out of the 11
      patients. RESULTS: Of the 14 patients under study, 5 (3 girls) had a
      translocation morphology TFE+ RCC, 2 were reassigned as papillary type 1 or 2,
      respectively, 2 tumor specimens with primary clear cell histology had confirmed
      the initial histologic diagnosis, and 2-whose biopsy specimen was insufficient
      had the diagnosis of RCC not further specified with subtyping. In the remaining 3
      cases, the initial diagnosis of clear cell carcinoma was left. Overall, 6
      patients received chemotherapy, 9 immunotherapy, and 2 adjuvant antiangiogenic
      therapy. Overall, 11 patients (78.5%) never achieved complete remission and died
      from progressive disease 1 to 16 months after diagnosis (median overall survival
      5.5 mo). Three patients, 2 of whom received adjuvant antiangiogenic therapy,
      relapsed to lung at 3, 6, and 8 months after diagnosis, and died 18, 32, and 33
      months after diagnosis, respectively. CONCLUSIONS: Despite their possibly
      different biology, childhood and adult mRCC seems to be sharing comparable
      outcomes. Because of the very low incidence of mRCC (about 20%) in children and
      adolescents, an international pediatric cooperation to address biological studies
      and assess the novel targeted approaches is needed.

PMID- 23007346
TI  - Hypereosinophilia:  more than meets the eye.
AB  - INTRODUCTION: Eosinophilia has myriad causes and is occaisonally seen in
      association with malignancies. Acute myeloid leukemia presenting with
      eosinophilia has rarely been reported in children. CASE: Authors herein present a
      case of a 5-year-old boy who presented with marked peripheral eosinophilia with
      symptoms of organ infiltration. Extensive work-up was needed before the diagnosis
      was established in this patient. DISCUSSION: Through this case report, we want to
      emphasize that peripheral eosinophilia could be a dilemma challenging clinical
      skills and often needing vigorous perusal for the diagnosis.

PMID- 23007347
TI  - Medicine is debate.

PMID- 23007353
TI  - The malnourished athlete--guidelines for interventions.

PMID- 23007354
TI  - [How to educate a sports cardiologist?].

PMID- 23007355
TI  - [Does the patient really have hypertension?].

PMID- 23007356
TI  - [Should brain injury markers replace CT in mild head injury?].

PMID- 23007358
TI  - Dementia and neuropsychiatric  symptoms in nursing-home patients in Nord
      Trondelag County.
AB  - BACKGROUND: Earlier studies have revealed a high prevalence of dementia among
      nursing home patients. We conducted a descriptive study of dementia and
      neuropsychiatric symptoms among patients in nursing homes in Nord-Trondelag
      County, Norway. MATERIAL AND METHODS: 704 nursing home patients were included and
      studied with the Norwegian versions of the clinical demential rating scale (CDR)
      and the neuropsychiatric inventory (NPI). RESULTS: The study indicated that 575
      patients (82%) had dementia. Of these, 430 patients (75%) had at least one
      clinically significant neuropsychiatric syndrome in addition, most commonly
      delusions, apathy or irritability. The neuropsychiatric symptoms could be grouped
      in four categories: psychosis, apathy, affective symptoms and agitation.
      INTERPRETATION: The findings are comparable with earlier studies of Norwegian
      nursing home patients. The high prevalence of dementia and neuropsychiatric
      symptoms is of significance for the clinical practice, running and planning of
      nursing homes.

PMID- 23007359
TI  - An unusual finding in  a case of ischialgia.

PMID- 23007360
TI  - [Hypersensitivity reactions to nonsteroidal  anti-inflammatory drugs].
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered  to be the second
      most frequent cause of adverse drug reactions,  including drug hypersensitivity,
      after beta-lactam antibiotics.  An understanding of the underlying mechanisms and
      clinical characteristics  of hypersensitivity reactions to NSAIDs is necessary
      for the diagnosis  and management of these undesirable reactions in the clinical
      setting.

PMID- 23007361
TI  - An infant's  failure to thrive ended in death.

PMID- 23007362
TI  - Unclear symptoms--fatal outcome.

PMID- 23007363
TI  - A woman in her seventies with reduced general condition, dyspnoea and generalised
      pain.

PMID- 23007364
TI  - Iron chelation therapy in myelodysplastic syndrome.

PMID- 23007365
TI  - [What is sports psychiatry?].

PMID- 23007366
TI  - [When sports and health collide].

PMID- 23007367
TI  - ["For information" should be avoided].

PMID- 23007368
TI  - [Verbiage].

PMID- 23007371
TI  - Clinical application of subjective measurements for OSAS assessment: predictive
      factors of syndrome severity.
AB  - PURPOSE OF THE STUDY: To examine the clinical value of subjective evaluations of
      obstructive sleep apnea syndrome (OSAS) in correlation with syndrome severity as
      diagnosed with polysomnography. PROCEDURES: 210 patients with mild to severe OSAS
      were assessed. Objective evaluation included polysomnography. Subjective
      assessment included full ENT examination, neck circumference (NC) plus body mass
      index measurements, Mueller maneuver and Epworth Symptom Scale (ESS). RESULTS:
      The presence of lateral pharyngeal wall movement, abnormal ESS scoring and male
      gender can be considered independent risk factors for the prediction of
      moderate/severe OSAS (p < 0.05). Increased NC can also be considered a clinical
      risk factor related to male gender and lateral pharyngeal wall movement (p =
      0.05). CONCLUSIONS: Subjective OSAS assessment, including evaluation of lateral
      pharyngeal wall movement, ESS scoring and NC measurement can safely predict,
      mainly in males, OSAS severity, as diagnosed with polysomnography. MESSAGE OF THE
      PAPER: Subjective assessment from the ENT point of view should raise high
      suspicion towards the early diagnosis of moderate/severe OSAS.

PMID- 23007372
TI  - A microarray for microRNA profiling in spermatozoa from adult men living in an
      environmentally polluted site.
AB  - We compared the miRNA expression profiles of spermatozoa from adult men living in
      an environment contaminated with electronic waste with those living in a normal
      environment, using a miRNA microarray. There were 73 significantly upregulated
      and 109 downregulated miRNAs in spermatozoa from men in the polluted environment
      compared with controls. Ten miRNAs were expressed significantly differently
      between the control and polluted samples and this result were further confirmed
      through quantitative real-time polymerase chain reaction amplification. A
      bioinformatics pipeline was developed to distinguish relationship with
      spermatogenesis. Our data indicated specific miRNAs expression of spermatozoa in
      men living in environmentally polluted sites and suggested that miRNAs have a
      role in regulating spermatogenesis. We also propose a subclassification scheme
      for miRNAs for assisting future experimental and computational functional
      analyses.

PMID- 23007373
TI  - Determining organic pollutants in automotive industry sludge.
AB  - In Brazil, the policy for disposing industrial sludge is changing from an
      emphasis on using controlled landfills to other treatment or co-processing
      methods; however, the monitoring of organic pollutants is not mandatory. The
      present study evaluated two general screening methods for organic pollutants in
      sludge generated in an automotive industrial complex in southern Brazil. The
      screening was performed using Soxhlet and sonication extractions and Gas
      Chromatograph coupled with Quadrupole Mass Spectrometry (GC/qMS). It was
      concluded that both techniques were effective and that most of the compounds
      identified were alkanes, phenols and esters. Important pollutants were detected
      in the sludge, which confirms the necessity of monitoring this type of residue.

PMID- 23007374
TI  - An electrochemical approach to simultaneous determination of acetaminophen and
      ofloxacin.
AB  - This study presents a simple electrochemical approach for preparing a poly(L
      serine) film-modified glassy carbon electrode, which responds quickly and
      sensitively during the simultaneous determination of acetaminophen and ofloxacin
      in prepared, environmental, and pharmaceutical samples. The prepared electrode
      exhibited catalytic activities and promoted the oxidation of acetaminophen and
      ofloxacin. Acetaminophen and ofloxacin showed linear responses between 1.0 * 10(
      5) and 1.0 * 10(-4) mol/L and their limits of detection were 1.2 * 10(-7) and 1.6
      * 10(-7) mol/L, respectively. The average recoveries (+/- relative standard
      deviations) of acetaminophen and ofloxacin were 96.8 +/- 3.5 % and 97.6 +/- 3.2
      %, respectively, indicating that the prepared electrode and detection method are
      very accurate and reproducible for the simultaneous determination of
      acetaminophen and ofloxacin.

PMID- 23007375
TI  - Comparison of historical record of PCDD/Fs, dioxin-like PCBs, and PCNs in
      sediment cores from Jiaozhou Bay and coastal Yellow Sea: implication of different
      sources.
AB  - The concentrations of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs),
      dioxin-like polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes
      (PCNs) were measured in two sediment cores collected from Jiaozhou Bay. The
      concentrations of PCDD/Fs, dioxin-like PCBs, and PCNs in the cores were in the
      range of 2.8-26.3, 7.1-82.4 and 3.9-56.4 pg/g dw, respectively. The depth
      profiles of total concentrations PCDD/Fs and dioxin-like PCBs were similar in the
      sediment core J37 inside Jiaozhou Bay, but different from those in the sediment
      core J94 outside the bay, suggesting the different sources. In both cores Tri-CNs
      and Tetra-CNs were dominant, similar to the PCNs composition of some Halowax
      technical products. The maximal PCNs contamination occurred in the mid-1970s
      (outside the Bay) and early-1990s (inside the Bay). An increase of the indicator
      CN congeners characteristic for thermal source in the top layers of the sediment
      core inside the bay indicated that the contribution from the municipal solid
      waste incineration has been more important in recent years.

PMID- 23007376
TI  - Desymmetrisation of meso-diols mediated by non-enzymatic acyl transfer catalysts.
AB  - Complementary to enzymatic methods, catalytic enantioselective desymmetrisation
      of meso-diols (EDMD) by small molecule catalysts has emerged as a powerful tool
      that provides highly enantioenriched materials of considerable value in organic
      synthesis. This review traces the evolution of easily accessible catalysts used
      in the EDMD and compares their performance with the existing enzymatic methods.

PMID- 23007377
TI  - Examining the relationship between processes of care and selected AHRQ patient
      safety indicators postoperative wound dehiscence and accidental puncture or
      laceration using the VA electronic medical record.
AB  - This study examines whether Agency for Healthcare Research and Quality Patient
      Safety Indicators (PSIs) Postoperative Wound Dehiscence (PWD) and Accidental
      Puncture or Laceration (APL) events reflect problems with hospital processes of
      care (POC). The authors randomly selected 112 PSI-flagged PWD/APL discharges from
      2002-2007 VA administrative data, identified true cases using chart review, and
      matched cases with controls. This yielded a total of 95 case-control pairs per
      PSI. Patient information and clinical processes on each case-control pair were
      abstracted from the electronic medical record (EMR). Although PWD cases and
      controls differed on incision and closure types, APL cases and controls were
      comparable in examined processes. Further exploration of the process differences
      between PWD cases and controls indicated that they were primarily caused by
      patients' underlying surgical problems rather than quality of care shortfalls.
      Documentation of POC was frequently missing in EMRs. Future studies should
      combine EMR review with alternative approaches, such as direct observation, to
      better assess POC.

PMID- 23007378
TI  - A model for peer experiential and reciprocal supervision (PEERS) for genetic
      counselors: development and preliminary evaluation within clinical practice.
AB  - A model for practising genetic counselors to obtain clinical supervision via
      reciprocal peer observation and feedback was developed and trialled. The model
      was developed in response to a perceived lack of opportunity for immediate
      observational feedback for practising genetic counselors. The aims reached by
      consensus were to facilitate learning new approaches and skills, to revitalise
      current ways of practising, and to enhance supervision skills in a two-way
      process, where the observer learnt from the counselor, and vice-versa. The
      genetic counselors agreed on a process of paired reciprocal observation whereby
      the observer was present in the room during the counseling session, and a
      reflective feedback discussion was arranged within 24 h of the session. Four main
      themes emerged from analysis of the recorded discussions were (i) "I wasn't sure
      if I-": voicing of doubts or internal questions that occurred during session for
      the counselor conducting the session, (ii) "I really liked that": positive
      feedback and validation from the observer, (iii) "I wonder whether-": offering of
      alternative views, insights and strategies by the observer, and (iv) "That's a
      real thing for me to take away and think about": evidence of learning by both
      observers and counselors.

PMID- 23007379
TI  - Transformation of solitary osteochondroma to dedifferentiated chondrosarcoma
      arising in the distal radius: a case report.
AB  - We present the case of a 35-year-old patient suffering from an untreated solitary
      osteochondroma and subsequent rare transformation to a dedifferentiated
      chondrosarcoma. This case highlights the potential risk of malignant
      transformation and raises the question of patient and clinician responsibility in
      identifying changes in a premalignant condition.

PMID- 23007380
TI  - Epidemiology of stroke in northern Italy: the Cerebrovascular Aosta Registry,
      2004-2008.
AB  - Our aim was to prospectively ascertain the incidence of first-ever stroke and
      ischaemic stroke subtypes, mortality, functional outcome and recurrence in
      northern Italy. We identified all possible cases of stroke (1st January 2004 and
      31st December 2008). Multiple overlapping sources were used. Standard definitions
      for incident cases, pathological types and infarction subtypes were used. Patient
      characteristics were identified and analysed, case-fatality was ascertained from
      administrative databases, and outcome was assessed in all surviving patients by
      modified Rankin Scale. We identified 1,326 incident strokes. The pathological
      diagnosis was confirmed in 94% of cases. The incidence of first-ever stroke was
      80.2 per 100,000 (95% CI 73-87) when adjusted to world population. The incidence
      of embolic stroke was significantly greater in women than in men (p < 0.001)
      whereas the incidence of atherothrombotic stroke was significantly greater in men
      than in women (p < 0.001). The case-fatality of incident strokes was 9.5% at 7
      day, 16.1% at 28 day, and 29.9% at 1 year. Case-fatality of ischaemic stroke was
      lower than that of other pathological types (p < 0.0001). Hypertension was the
      most important risk factor, and atrial fibrillation was the most common in
      embolic stroke. Increasing age, female gender and embolic stroke subtypes were
      associated with an adverse outcome. Data on stroke incidence and case-fatality
      were similar to those of other high-income countries. However, differences were
      found in the distribution of risk factors and prognosis across the stroke types
      and ischaemic stroke subtypes. Gender differences in long-term functional
      outcomes were significant.

PMID- 23007381
TI  - Immunotherapy in Rasmussen's encephalitis: when should it be taken into account?

PMID- 23007382
TI  - Coping with critical drug shortages: an ethical approach for allocating scarce
      resources in hospitals.
AB  - The number of critical medication shortages in the United States has reached an
      unprecedented level, requiring decisions about allocating limited drug supplies.
      Ad hoc decisions are susceptible to arbitrary judgments, revealing preformed
      biases for or against groups of people. Health care institutions lack
      standardized protocols for rationing scarce drugs. We describe the principles on
      which an ethically justifiable policy of medication allocation during critical
      shortages was created at our hospital. Based on supportable scientific evidence
      and with all clinically similar patients treated as similarly deserving of
      consideration, drugs were distributed according to a hierarchy of clinical need
      and predicted efficacy. We explain the ethical rationale for the procedures we
      adopted, how the policy was implemented at a large academic medical center, and
      more than 1 year of experience with a number of different medications. Our
      experience has demonstrated the feasibility and utility of formulating a rational
      and ethically sound policy for scarce resource allocation in an academic teaching
      hospital that could be used in a variety of health care settings. The method has
      proven to be reliable, workable, and acceptable to clinicians, staff, and
      patients.

PMID- 23007383
TI  - Value of preoperative biliary drainage in a consecutive series of resectable
      periampullary lesions. From randomized studies to real medical practice.
AB  - BACKGROUND: In cases with periampullary tumors, the practice of preoperative
      biliary drainage (PBD) is still debated without clear uniform indications. Our
      study focused on resectable cases with an obstructive jaundice candidate for
      curative surgery. Main endpoints were overall complication and mortality rates
      between patients treated with and without PBD. METHODS: From January 2008 to
      November 2010, 100 consecutive patients with periampullary lesion underwent
      pancreatectomy. The rates of postoperative complications and mortality were
      compared between PBD and non-PBD patients. RESULTS: The two groups were well
      matched for demographics, clinical, and operative characteristics. In patients
      who completed preoperative PBD protocol, biliary stent was placed systematically
      in 45 % of these cases without any clear indication. Post-PBD complication
      delayed surgery in 24 % of cases. Postoperative complications did not differ
      significantly between the two groups except for a significantly higher positive
      bile culture in PBD group (p = 0.001). There were seven cases of hospital
      mortality, four in PBD and three in non-PBD group. DFS was equal (32 months) in
      both groups (p = 0.55), and OS was 43 vs 32 months (p = 0.45). CONCLUSION: PBD
      did not significantly increase the risk of overall postoperative complications,
      although it was associated to higher rate of biliary infections. PBD was not
      associated with any advantages in patients with a resectable periampullary lesion
      by reducing operative morbidity. PBD should be considered in selected patients
      when surgery has to be delayed.

PMID- 23007385
TI  - Gene regulation: RNAs feel the heat.

PMID- 23007384
TI  - Cinacalcet effects on the perioperative course of patients with secondary
      hyperparathyroidism.
AB  - PURPOSE: Since its registration in 2004, the calcimimetic agent cinacalcet has
      been established as an alternative treatment for secondary hyperparathyroidism
      (SHPT). Working by allosteric activation of the calcium-sensing receptor,
      cinacalcet can lower parathyroid hormone (PTH) and calcium (Ca) in patients with
      SHPT. The influence of calcimimetics on the perioperative course has been unclear
      so far. METHODS: We retrospectively analyzed the data of patients with primary
      operation for SHPT between 2004 and 2011, comparing the perioperative course of
      patients with and without preoperative cinacalcet treatment. RESULTS: Fifty-six
      patients had cinacalcet therapy, and 54 patients had no calcimimetic medication
      prior to surgery. Gender, age, hemodialysis, and medical treatment were similar
      in both groups. Also, PTH levels were similar preoperatively and postoperatively
      (preoperative, 1,249 +/- 676 vs. 1,196 +/- 601 pg/ml; postoperative, 86 +/- 220
      vs. 62 +/- 91 pg/ml). Patients with cinacalcet preoperatively had significant
      lower Ca levels preoperatively (2.49 +/- 0.25 vs. 2.61 +/- 0.24 mmol/l) and
      postoperatively (1.75 +/- 0.37 vs. 1.86 +/- 0.35 mmol/l) and had a higher rate of
      oral Ca substitution postoperatively (93 vs. 74 %). The risk for postoperative
      persistent disease was slightly higher in these patients compared to those
      without preoperative cinacalcet therapy (5 vs. 0 %, not significant).
      CONCLUSIONS: In our experience, cinacalcet did not alter the perioperative course
      in SHPT patients.

PMID- 23007386
TI  - Plant genetics: a killer-protector mechanism in hybrid sterility.

PMID- 23007387
TI  - Membrane fusion triggering: three modules with different structure and function
      in the upper half of the measles virus attachment protein stalk.
AB  - The measles virus (MV) fusion apparatus consists of a fusion protein and an
      attachment protein named hemagglutinin (H). After receptor-binding through its
      cuboidal head, the H-protein transmits the fusion-triggering signal through its
      stalk to the fusion protein. However, the structural basis of signal transmission
      is unclear because only structures of H-heads without their stalk have been
      solved. On the other hand, the entire ectodomain structure of the hemagglutinin
      neuraminidase protein of another Paramyxovirus revealed a four-helix bundle
      stalk. To probe the structure of the 95-residue MV H-stalk we individually
      substituted head-proximal residues (positions 103-153) with cysteine, and
      biochemically and functionally characterized the resultant proteins. Our results
      indicate that most residues in the central segment (positions 103-117) can be
      cross-linked by engineered disulfide bonds, and thus may be engaged in a
      tetrameric structure. While covalent tetramerization disrupts fusion triggering
      function, disulfide bond reduction restores it in most positions except Asp-113.
      The next stalk segment (residues 123-138) also has high propensity to form
      covalent tetramers, but since these cross-links have little or no effect on
      function, it can conduct the fusion-triggering signal while remaining in a
      stabilized tetrameric configuration. This segment may act as a spacer,
      maintaining H-heads at an optimal height. Finally, the head-proximal segment
      (residues 139-154) has very limited propensity to trap tetramers, suggesting
      bifurcation into two flexible linkers clamped by inter-subunit covalent links
      formed by natural Cys-139 and Cys-154. We discuss the modular structure of the MV
      H-stalk in the context of membrane fusion triggering and cell entry by
      Paramyxoviruses.

PMID- 23007388
TI  - A c subunit with four transmembrane helices and one ion (Na+)-binding site in an
      archaeal ATP synthase: implications for c ring function and structure.
AB  - The ion-driven membrane rotors of ATP synthases consist of multiple copies of
      subunit c, forming a closed ring. Subunit c typically comprises two transmembrane
      helices, and the c ring features an ion-binding site in between each pair of
      adjacent subunits. Here, we use experimental and computational methods to study
      the structure and specificity of an archaeal c subunit more akin to those of V
      type ATPases, namely that from Pyrococcus furiosus. The c subunit was purified by
      chloroform/methanol extraction and determined to be 15.8 kDa with four predicted
      transmembrane helices. However, labeling with DCCD as well as Na(+)-DCCD
      competition experiments revealed only one binding site for DCCD and Na(+),
      indicating that the mature c subunit of this A(1)A(O) ATP synthase is indeed of
      the V-type. A structural model generated computationally revealed one Na(+)
      binding site within each of the c subunits, mediated by a conserved glutamate
      side chain alongside other coordinating groups. An intriguing second glutamate
      located in-between adjacent c subunits was ruled out as a functional Na(+)
      binding site. Molecular dynamics simulations indicate that the c ring of P.
      furiosus is highly Na(+)-specific under in vivo conditions, comparable with the
      Na(+)-dependent V(1)V(O) ATPase from Enterococcus hirae. Interestingly, the same
      holds true for the c ring from the methanogenic archaeon Methanobrevibacter
      ruminantium, whose c subunits also feature a V-type architecture but carry two
      Na(+)-binding sites instead. These findings are discussed in light of their
      physiological relevance and with respect to the mode of ion coupling in A(1)A(O)
      ATP synthases.

PMID- 23007389
TI  - The Nup153-Nup50 protein interface and its role in nuclear import.
AB  - Interactions between Nup50 and soluble transport factors underlie the efficiency
      of certain nucleocytoplasmic transport pathways. The platform on which these
      interactions take place is important to building a complete understanding of
      nucleocytoplasmic trafficking. Nup153 is the nucleoporin that provides this
      scaffold for Nup50. Here, we have delineated requirements for the interaction
      between Nup153 and Nup50, revealing a dual interface. An interaction between
      Nup50 and a region in the unique N-terminal region of Nup153 is critical for the
      nuclear pore localization of Nup50. A second site of interaction is at the distal
      tail of Nup153 and is dependent on importin alpha. Both of these interactions
      involve the N-terminal domain of Nup50. The configuration of the Nup153-Nup50
      partnership suggests that the Nup153 scaffold provides not just a means of pore
      targeting for Nup50 but also serves to provide a local environment that
      facilitates bringing Nup50 and importin alpha together, as well as other soluble
      factors involved in transport. Consistent with this, disruption of the Nup153
      Nup50 interface decreases efficiency of nuclear import.

PMID- 23007390
TI  - Glucose modulates respiratory complex I activity in response to acute
      mitochondrial dysfunction.
AB  - Proper coordination between glycolysis and respiration is essential, yet the
      regulatory mechanisms involved in sensing respiratory chain defects and modifying
      mitochondrial functions accordingly are unclear. To investigate the nature of
      this regulation, we introduced respiratory bypass enzymes into cultured human
      (HEK293T) cells and studied mitochondrial responses to respiratory chain
      inhibition. In the absence of respiratory chain inhibitors, the expression of
      alternative respiratory enzymes did not detectably alter cell physiology or
      mitochondrial function. However, in permeabilized cells NDI1 (alternative NADH
      dehydrogenase) bypassed complex I inhibition, whereas alternative oxidase (AOX)
      bypassed complex III or IV inhibition. In contrast, in intact cells the effects
      of the AOX bypass were suppressed by growth on glucose, whereas those produced by
      NDI1 were unaffected. Moreover, NDI1 abolished the glucose suppression of AOX
      driven respiration, implicating complex I as the target of this regulation. Rapid
      Complex I down-regulation was partly released upon prolonged respiratory
      inhibition, suggesting that it provides an "emergency shutdown" system to
      regulate metabolism in response to dysfunctions of the oxidative phosphorylation.
      This system was independent of HIF1, mitochondrial superoxide, or ATP synthase
      regulation. Our findings reveal a novel pathway for adaptation to mitochondrial
      dysfunction and could provide new opportunities for combatting diseases.

PMID- 23007391
TI  - Acetylation of myocardin is required for the activation of cardiac and smooth
      muscle genes.
AB  - Myocardin belongs to the SAF-A/B, Acinus, PIAS (SAP) domain family of
      transcription factors and is specifically expressed in cardiac and smooth muscle.
      Myocardin functions as a transcriptional coactivator of SRF and is sufficient and
      necessary for smooth muscle gene expression. We have previously found that
      myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding
      sites in the control regions of cardiac and smooth muscle genes through
      recruiting chromatin-modifying enzyme p300, yet no studies have determined
      whether myocardin itself is similarly modified. In this study, we show that
      myocardin is a direct target for p300-mediated acetylation. p300 acetylates
      lysine residues at the N terminus of the myocardin protein. Interestingly, a
      direct interaction between p300 and myocardin, which is mediated by the C
      terminus of myocardin, is required for the acetylation event. Acetylation of
      myocardin by p300 enhances the association of myocardin and SRF as well as the
      formation of the myocardin-SRF-CArG box ternary complex. Conversely, acetylation
      of myocardin decreases the binding of histone deacetylase 5 (HDAC5) to myocardin.
      Acetylation of myocardin is required for myocardin to activate smooth muscle
      genes. Our study demonstrates that acetylation plays a key role in modulating
      myocardin function in controlling cardiac and smooth muscle gene expression.

PMID- 23007392
TI  - Characterization of a Phanerochaete chrysosporium glutathione transferase reveals
      a novel structural and functional class with ligandin properties.
AB  - Glutathione S-transferases (GSTs) form a superfamily of multifunctional proteins
      with essential roles in cellular detoxification processes. A new fungal specific
      class of GST has been highlighted by genomic approaches. The biochemical and
      structural characterization of one isoform of this class in Phanerochaete
      chrysosporium revealed original properties. The three-dimensional structure
      showed a new dimerization mode and specific features by comparison with the
      canonical GST structure. An additional beta-hairpin motif in the N-terminal
      domain prevents the formation of the regular GST dimer and acts as a lid, which
      closes upon glutathione binding. Moreover, this isoform is the first described
      GST that contains all secondary structural elements, including helix alpha4' in
      the C-terminal domain, of the presumed common ancestor of cytosolic GSTs (i.e.
      glutaredoxin 2). A sulfate binding site has been identified close to the
      glutathione binding site and allows the binding of 8-anilino-1-naphtalene
      sulfonic acid. Competition experiments between 8-anilino-1-naphtalene sulfonic
      acid, which has fluorescent properties, and various molecules showed that this
      GST binds glutathionylated and sulfated compounds but also wood extractive
      molecules, such as vanillin, chloronitrobenzoic acid, hydroxyacetophenone,
      catechins, and aldehydes, in the glutathione pocket. This enzyme could thus
      function as a classical GST through the addition of glutathione mainly to
      phenethyl isothiocyanate, but alternatively and in a competitive way, it could
      also act as a ligandin of wood extractive compounds. These new structural and
      functional properties lead us to propose that this GST belongs to a new class
      that we name GSTFuA, for fungal specific GST class A.

PMID- 23007393
TI  - Chondroitin sulfate is a crucial determinant for skeletal muscle
      development/regeneration and improvement of muscular dystrophies.
AB  - Skeletal muscle formation and regeneration require myoblast fusion to form
      multinucleated myotubes or myofibers, yet their molecular regulation remains
      incompletely understood. We show here that the levels of extra- and/or
      pericellular chondroitin sulfate (CS) chains in differentiating C2C12 myoblast
      culture are dramatically diminished at the stage of extensive syncytial myotube
      formation. Forced down-regulation of CS, but not of hyaluronan, levels enhanced
      myogenic differentiation in vitro. This characteristic CS reduction seems to
      occur through a cell-autonomous mechanism that involves HYAL1, a known catabolic
      enzyme for hyaluronan and CS. In vivo injection of a bacterial CS-degrading
      enzyme boosted myofiber regeneration in a mouse cardiotoxin-induced injury model
      and ameliorated dystrophic pathology in mdx muscles. Our data suggest that the
      control of CS abundance is a promising new therapeutic approach for the treatment
      of skeletal muscle injury and progressive muscular dystrophies.

PMID- 23007394
TI  - A HIC-5- and KLF4-dependent mechanism transactivates p21(Cip1) in response to
      anchorage loss.
AB  - Anchorage loss elicits a set of responses in cells, such as transcriptional
      changes, in order to prevent inappropriate cell growth in ectopic environments.
      However, the mechanisms underlying these responses are poorly understood. In this
      study, we investigated the transcriptional up-regulation of cyclin-dependent
      kinase inhibitor p21(Cip1) during anchorage loss, which is important for cell
      cycle arrest of nonadherent cells in the G1 phase. Up-regulation was mediated by
      an upstream element, designated as the detachment-responsive element (DRE), that
      contained Kruppel-like factor 4 (KLF4) and runt-related transcription factor 1
      (RUNX1) recognition sites; both of these together were necessary for
      transactivation, as individually they were insufficient. RNAi experiments
      revealed that KLF4 and a multidomain adaptor protein, hydrogen peroxide-inducible
      clone 5 (HIC-5), were critically involved in DRE transactivation. The role of HIC
      5 in this mechanism was to tether KLF4 to DNA sites in response to cellular
      detachment. In addition, further analysis suggested that oligomerization and
      subsequent nuclear matrix localization of HIC-5, which was accelerated
      spontaneously in cells during anchorage loss, was assumed to potentiate the
      scaffolding function of HIC-5 in the nucleus and consequently regulate p21(Cip1)
      transcription in a manner responding to anchorage loss. At the RUNX1 site, a LIM
      only protein, CRP2, imposed negative regulation on transcription, which appeared
      to be removed by anchorage loss and contributed to increased transcriptional
      activity of DRE together with regulation at the KLF4 sites. In conclusion, this
      study revealed a novel transcriptional mechanism that regulated gene expression
      in a detachment-dependent manner, thereby contributing to anchorage-dependent
      cell growth.

PMID- 23007395
TI  - Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates
      the development of proneural glioma.
AB  - Phosphorylation of Tyr-88/Tyr-89 in the 3(10) helix of p27 reduces its cyclin
      dependent kinase (CDK) inhibitory activity. This modification does not affect the
      interaction of p27 with cyclin-CDK complexes but does interfere with van der
      Waals and hydrogen bond contacts between p27 and amino acids in the catalytic
      cleft of the CDK. Thus, it had been suggested that phosphorylation of this site
      could switch the tumor-suppressive CDK inhibitory activity to an oncogenic
      activity. Here, we examined this hypothesis in the RCAS-PDGF-HA/nestin-TvA
      proneural glioma mouse model, in which p21 facilitates accumulation of nuclear
      cyclin D1-CDK4 and promotes tumor development. In these tumor cells,
      approximately one-third of the p21 is phosphorylated at Tyr-76 in the 3(10)
      helix. Mutation of this residue to glutamate reduced inhibitory activity in
      vitro. Mutation of this residue to phenylalanine reduced the tumor-promoting
      activity of p21 in the animal model, whereas glutamate or alanine substitution
      allowed tumor formation. Consequently, we conclude that tyrosine phosphorylation
      contributes to the conversion of CDK inhibitors from tumor-suppressive roles to
      oncogenic roles.

PMID- 23007396
TI  - Cutaneous retinoic acid levels determine hair follicle development and
      downgrowth.
AB  - Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis,
      whereas excess RA is well known as a teratogen. In humans, excess RA is
      associated with hair loss. In the present study, we demonstrate that specific
      levels of RA, regulated by Cyp26b1, one of the RA-degrading enzymes, are required
      for hair follicle (hf) morphogenesis. Mice with embryonic ablation of Cyp26b1
      (Cyp26b1(-/-)) have excessive endogenous RA, resulting in arrest of hf growth at
      the hair germ stage. The altered hf development is rescued by grafting the mutant
      skin on immunodeficient mice. Our results show that normalization of RA levels is
      associated with reinitiation of hf development. Conditional deficiency of Cyp26b1
      in the dermis (En1Cre;Cyp26b1f/-) results in decreased hair follicle density and
      specific effect on hair type, indicating that RA levels also influence regulators
      of hair bending. Our results support the model of RA-dependent dermal signals
      regulating hf downgrowth and bending. To elucidate target gene pathways of RA, we
      performed microarray and RNA-Seq profiling of genes differentially expressed in
      Cyp26b1(-/-) skin and En1Cre;Cyp26b1f/- tissues. We show specific effects on the
      Wnt-catenin pathway and on members of the Runx, Fox, and Sox transcription factor
      families, indicating that RA modulates pathways and factors implicated in hf
      downgrowth and bending. Our results establish that proper RA distribution is
      essential for morphogenesis, development, and differentiation of hfs.

PMID- 23007397
TI  - Disruption of wave-associated Rac GTPase-activating protein (Wrp) leads to
      abnormal adult neural progenitor migration associated with hydrocephalus.
AB  - Hydrocephalus is the most common developmental disability and leading cause of
      brain surgery for children. Current treatments are limited to surgical
      intervention, as the factors that contribute to the initiation of hydrocephalus
      are poorly understood. Here, we describe the development of obstructive
      hydrocephalus in mice that are null for Wrp (Srgap3). Wrp is highly expressed in
      the ventricular stem cell niche, and it is a gene required for cytoskeletal
      organization and is associated with syndromic and psychiatric disorders in
      humans. During the postnatal period of progenitor cell expansion and ventricular
      wall remodeling, loss of Wrp results in the abnormal migration of lineage-tagged
      cells from the ventricular region into the corpus callosum. Within this region,
      mutant progenitors appear to give rise to abnormal astroglial cells and induce
      periventricular lesions and hemorrhage that leads to cerebral aqueductal
      occlusion. These results indicate that periventricular abnormalities arising from
      abnormal migration from the ventricular niche can be an initiating cause of
      noncommunicating hydrocephalus.

PMID- 23007398
TI  - Steric hindrance mutagenesis in the conserved extracellular vestibule impedes
      allosteric binding of antidepressants to the serotonin transporter.
AB  - The serotonin transporter (SERT) controls synaptic serotonin levels and is the
      primary target for antidepressants, including selective serotonin reuptake
      inhibitors (e.g. (S)-citalopram) and tricyclic antidepressants (e.g.
      clomipramine). In addition to a high affinity binding site, SERT possesses a low
      affinity allosteric site for antidepressants. Binding to the allosteric site
      impedes dissociation of antidepressants from the high affinity site, which may
      enhance antidepressant efficacy. Here we employ an induced fit docking/molecular
      dynamics protocol to identify the residues that may be involved in the allosteric
      binding in the extracellular vestibule located above the central substrate
      binding (S1) site. Indeed, mutagenesis of selected residues in the vestibule
      reduces the allosteric potency of (S)-citalopram and clomipramine. The identified
      site is further supported by the inhibitory effects of Zn(2+) binding in an
      engineered site and the covalent attachment of benzocaine-methanethiosulfonate to
      a cysteine introduced in the extracellular vestibule. The data provide a
      mechanistic explanation for the allosteric action of antidepressants at SERT and
      suggest that the role of the vestibule is evolutionarily conserved among
      neurotransmitter:sodium symporter proteins as a binding pocket for small molecule
      ligands.

PMID- 23007399
TI  - A rapid, comprehensive liquid chromatography-mass spectrometry (LC-MS)-based
      survey of the Asp isomers in crystallins from human cataract lenses.
AB  - Cataracts are caused by clouding of the eye lens and may lead to partial or total
      loss of vision. The mechanism of cataract development, however, is not well
      understood. It is thought that abnormal aggregates of lens proteins form with
      age, causing loss of lens clarity and development of the cataract. Lens proteins
      are composed of soluble alpha-, beta-, and gamma-crystallins, and as long lived
      proteins, they undergo post-translational modifications including isomerization,
      deamidation, and oxidation, which induce insolubilization, aggregation, and loss
      of function that may lead to cataracts. Therefore, analysis of post-translational
      modifications of individual amino acid residues in proteins is important.
      However, detection of the optical isomers of amino acids formed in these proteins
      is difficult because optical resolution is only achieved using complex
      methodology. In this study, we describe a new method for the analysis of
      isomerization of individual Asp residues in proteins using LC-MS and the
      corresponding synthetic peptides containing the Asp isomers. This makes it
      possible to analyze isomers of Asp residues in proteins precisely and quickly. We
      demonstrate that Asp-58, -76, -84, and -151 of alphaA-crystallin and Asp-62 and 
      96 of alphaB-crystallin are highly converted to lbeta-, dbeta-, and dalpha
      isomers. The amount of isomerization of Asp is greater in the insoluble fraction
      at all Asp sites in lens proteins, therefore indicating that isomerization of
      these Asp residues affects the higher order structure of the proteins and
      contributes to the increase in aggregation, insolubilization, and disruption of
      function of proteins in the lens, leading to the cataract.

PMID- 23007400
TI  - Roles of acidic phospholipids and nucleotides in regulating membrane binding and
      activity of a calcium-independent phospholipase A2 isoform.
AB  - Phospholipase A(2) activity plays key roles in generating lipid second messengers
      and regulates membrane topology through the generation of asymmetric
      lysophospholipids. In particular, the Group VIA phospholipase A(2) (GVIA-iPLA(2))
      subfamily of enzymes functions independently of calcium within the cytoplasm of
      cells and has been implicated in numerous cellular processes, including
      proliferation, apoptosis, and membrane transport steps. However, mechanisms
      underlying the spatial and temporal regulation of these enzymes have remained
      mostly unexplored. Here, we examine the subset of Caenorhabditis elegans lipases
      that harbor a consensus motif common to members of the GVIA-iPLA(2) subfamily.
      Based on sequence homology, we identify IPLA-1 as the closest C. elegans homolog
      of human GVIA-iPLA(2) enzymes and use a combination of liposome interaction
      studies to demonstrate a role for acidic phospholipids in regulating GVIA-iPLA(2)
      function. Our studies indicate that IPLA-1 binds directly to multiple acidic
      phospholipids, including phosphatidylserine, phosphatidylglycerol, cardiolipin,
      phosphatidic acid, and phosphorylated derivatives of phosphatidylinositol.
      Moreover, the presence of these acidic lipids dramatically elevates the specific
      activity of IPLA-1 in vitro. We also found that the addition of ATP and ADP
      promote oligomerization of IPLA-1, which probably underlies the stimulatory
      effect of nucleotides on its activity. We propose that membrane composition and
      the presence of nucleotides play key roles in recruiting and modulating GVIA
      iPLA(2) activity in cells.

PMID- 23007401
TI  - Life in a three-dimensional grid.
AB  - There have been two sharp demarcations in my life in science: the transition from
      fine arts to chemistry, which happened early in my career, and the move from New
      York to Stanford University, which initiated an ongoing collaboration with the
      physicist Harley McAdams. Both had a profound effect on the kinds of questions I
      posed and the means I used to arrive at answers. The outcome of these
      experiences, together with the extraordinary scientists I came to know along the
      way, was and is an abiding passion to fully understand a simple cell in all its
      complexity and beauty.

PMID- 23007402
TI  - Epidermal growth factor (EGF) regulates alpha5beta1 integrin activation state in
      human cancer cell lines through the p90RSK-dependent phosphorylation of filamin
      A.
AB  - BACKGROUND: Regulation of integrin activation has important implications for
      tumor cell invasion and metastasis. RESULTS: EGF activates ERK/p90RSK and Rho/Rho
      kinase signaling in A431 and DiFi colon cancer cells, leading to phosphorylation
      of filamin A (FLNa) and inactivation of the alpha5beta1 integrin receptor.
      CONCLUSION: EGF promotes alpha5beta1 inactivation through the p90RSK-dependent
      phosphorylation of FLNa. SIGNIFICANCE: We have identified a novel EGF-dependent
      mechanism controlling the alpha5beta1 integrin activation state. Cell adhesion,
      motility, and invasion are regulated by the ligand-binding activity of integrin
      receptors, transmembrane proteins that bind to the extracellular matrix.
      Integrins whose conformation allows for ligand binding and appropriate functional
      activity are said to be in an active state. Integrin activation and subsequent
      ligand binding are dynamically regulated by the association of cytoplasmic
      proteins with integrin intracellular domains. In this study, we evaluated the
      role of EGF in the regulation of the activation state of the alpha5beta1 integrin
      receptor for fibronectin. The addition of EGF to either A431 squamous carcinoma
      cells or DiFi colon cancer cells resulted in loss of alpha5beta1-dependent
      adhesion to fibronectin but no loss of integrin from the cell surface. EGF
      activated the EGF receptor/ERK/p90RSK and Rho/Rho kinase signaling pathways.
      Blocking either pathway inhibited EGF-mediated loss of adhesion, suggesting that
      they work in parallel to regulate integrin function. EGF treatment also resulted
      in phosphorylation of filamin A (FLNa), which binds and inactivates beta1
      integrins. EGF-mediated FLNa phosphorylation was completely blocked by an
      inhibitor of p90RSK and partially attenuated by an inhibitor of Rho kinase,
      suggesting that both pathways converge on FLNa to regulate integrin function.
      A431 clonal cell lines expressing non-phosphorylated dominant-negative FLNa were
      resistant to the inhibitory effects of EGF on integrin function, whereas clonal
      cell lines overexpressing wild-type FLNa were more sensitive to the inhibitory
      effect of EGF. These data suggest that EGF-dependent inactivation of alpha5beta1
      integrin is regulated through FLNa phosphorylation and cellular contractility.

PMID- 23007403
TI  - Semaphorin 6A regulates angiogenesis by modulating VEGF signaling.
AB  - Formation of new vessels during development and in the mature mammal generally
      proceeds through angiogenesis. Although a variety of molecules and signaling
      pathways are known to underlie endothelial cell sprouting and remodeling during
      angiogenesis, many aspects of this complex process remain unexplained. Here we
      show that the transmembrane semaphorin6A (Sema6A) is expressed in endothelial
      cells, and regulates endothelial cell survival and growth by modulating the
      expression and signaling of VEGFR2, which is known to maintain endothelial cell
      viability by autocrine VEGFR signaling. The silencing of Sema6A in primary
      endothelial cells promotes cell death that is not rescued by exogenous VEGF-A or
      FGF2, attributable to the loss of prosurvival signaling from endogenous VEGF.
      Analyses of mouse tissues demonstrate that Sema6A is expressed in angiogenic and
      remodeling vessels. Mice with null mutations of Sema6A exhibit significant
      defects in hyaloid vessels complexity associated with increased endothelial cell
      death, and in retinal vessels development that is abnormally reduced. Adult
      Sema6A-null mice exhibit reduced tumor, matrigel, and choroidal angiogenesis
      compared with controls. Sema6A plays important roles in development of the
      nervous system. Here we show that it also regulates vascular development and
      adult angiogenesis.

PMID- 23007404
TI  - Human red blood cells at work: identification and visualization of erythrocytic
      eNOS activity in health and disease.
AB  - A nitric oxide synthase (NOS)-like activity has been demonstrated in human red
      blood cells (RBCs), but doubts about its functional significance, isoform
      identity and disease relevance remain. Using flow cytometry in combination with
      the nitric oxide (NO)-imaging probe DAF-FM we find that all blood cells form NO
      intracellularly, with a rank order of monocytes > neutrophils > lymphocytes >
      RBCs > platelets. The observation of a NO-related fluorescence within RBCs was
      unexpected given the abundance of the NO-scavenger oxyhemoglobin. Constitutive
      normoxic NO formation was abolished by NOS inhibition and intracellular NO
      scavenging, confirmed by laser-scanning microscopy and unequivocally validated by
      detection of the DAF-FM reaction product with NO using HPLC and LC-MS/MS. Using
      immunoprecipitation, ESI-MS/MS-based peptide sequencing and enzymatic assay we
      further demonstrate that human RBCs contain an endothelial NOS (eNOS) that
      converts L-(3)H-arginine to L-(3)H-citrulline in a Ca(2+)/calmodulin-dependent
      fashion. Moreover, in patients with coronary artery disease, red cell eNOS
      expression and activity are both lower than in age-matched healthy individuals
      and correlate with the degree of endothelial dysfunction. Thus, human RBCs
      constitutively produce NO under normoxic conditions via an active eNOS isoform,
      the activity of which is compromised in patients with coronary artery disease.

PMID- 23007405
TI  - Conditioning regimens for allotransplants for diffuse large B-cell lymphoma:
      myeloablative or reduced intensity?
AB  - The best conditioning regimen before allogeneic transplantation for high-risk
      diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data
      from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n
      = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC;
      n = 88) regimens. Acute and chronic GVHD rates were similar across the groups.
      Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs
      47% vs 36%; P = .007). Five-year relapse/progression was lower in MAC than in
      RIC/NMAC (26% vs 38% vs 40%; P = .031). Five-year progression-free survival (15%
      25%) and overall survival (18%-26%) did not differ significantly between the
      cohorts. In multivariate analysis, NMAC and more recent transplant year were
      associated with lower NRM, whereas a lower Karnofsky performance score (< 90),
      prior relapse resistant to therapy, and use of unrelated donors were associated
      with higher NRM. NMAC transplants, no prior use of rituximab, and prior relapse
      resistant to therapy were associated with a greater risk of relapse/progression.
      In conclusion, allotransplantation with RIC or NMAC induces long-term progression
      free survival in selected DLBCL patients with a lower risk of NRM but with higher
      risk of lymphoma progression or relapse.

PMID- 23007406
TI  - Genome-wide association study identifies germline polymorphisms associated with
      relapse of childhood acute lymphoblastic leukemia.
AB  - With the use of risk-directed therapy for childhood acute lymphoblastic leukemia
      (ALL), outcome has improved dramatically in the past 40 years. However, a
      substantial portion of patients, many of whom have no known risk factors,
      experience relapse. Taking a genome-wide approach, in the present study, we
      evaluated the relationships between genotypes at 444 044 single nucleotide
      polymorphisms (SNPs) with the risk of relapse in 2535 children with newly
      diagnosed ALL after adjusting for genetic ancestry and treatment regimen. We
      identified 134 SNPs that were reproducibly associated with ALL relapse. Of 134
      relapse SNPs, 133 remained prognostic after adjusting for all known relapse risk
      factors, including minimal residual disease, and 111 were significant even among
      patients who were negative for minimal residual disease after remission induction
      therapy. The C allele at rs7142143 in the PYGL gene was associated with 3.6-fold
      higher risk of relapse than the T allele (P = 6.7 * 10(-9)). Fourteen of the 134
      relapse SNPs, including variants in PDE4B and ABCB1, were also associated with
      antileukemic drug pharmacokinetics and/or pharmacodynamics. In the present study,
      we systematically identified host genetic variations related to treatment outcome
      of childhood ALL, most of which were prognostic independent of known risk factors
      for relapse, and some of which also influenced outcome by affecting host dis
      position of antileukemic drugs. All trials are registered at
      www.clinicaltrials.gov or www.cancer.gov (COG P9904: NCT00005585; COG P9905:
      NCT00005596; COG P9906: NCT00005603; St Jude Total XIIIB: NCI-T93-0101D; and St
      Jude Total XV: NCT00137111).

PMID- 23007407
TI  - A prospective study of circulating adipokine levels and risk of multiple myeloma.
AB  - It has been hypothesized that the observed excess risk of multiple myeloma (MM)
      among obese persons could be the result of altered circulating levels of
      adipokines, polypeptide hormones with pro- and anti-inflammatory properties
      secreted by adipose tissue. We investigated whether circulating levels of leptin,
      total adiponectin, and high molecular weight adiponectin are associated with
      subsequent MM risk among 174 MM patients and 348 controls within the Prostate,
      Lung, Colorectal, and Ovarian Cancer Screening Trial. Inverse associations with
      MM were observed for total adiponectin (highest quartile vs lowest: odds ratio =
      0.49; 95% CI = 0.26-0.93, P(trend) = .03) and high molecular weight adiponectin
      (0.44; 0.23-0.85, P(trend) = .01). These associations remained after restricting
      to MM patients diagnosed ~ 8 years or more after blood collection. Leptin levels
      were not associated with MM risk. The results of this study, to our knowledge the
      first prospective investigation of circulating adipokines and MM, suggest that
      adiponectin may play an important role in obesity-related myelomagenesis.

PMID- 23007408
TI  - Decreased levels of nitric oxide production and nitric oxide synthase-2
      expression are associated with the development and metastasis of hepatocellular
      carcinoma.
AB  - Many studies have demonstrated the function of nitric oxide (NO) or nitric oxide
      synthase-2 (NOS-2) in cancer as pro-neoplastic or anti-neoplastic effectors, but
      the role of NO and NOS-2 in hepatocellular carcinoma (HCC) remains unclear. The
      aim of this study was to investigate the levels of NO production and NOS-2
      expression in HCC and adjacent non-tumor liver tissues and to clarify whether the
      levels of NO/NOS-2 are related to the clinicopathological features of HCC. The
      levels of NO production were examined in tumor and adjacent non-tumor liver
      tissues of 30 patients with HCC. The expression of NOS-2 was detected by real
      time polymerase chain reaction (RT-PCR) and immunohistochemical analysis in HCC
      and/or adjacent non-tumor liver tissues. Mutant p53 and proliferating cell
      nuclear antigen (PCNA) were also immunohistochemically investigated in liver
      tissues. The levels of NO in HCC were significantly lower compared to adjacent
      non-tumor liver tissues (P<0.001). The relative mRNA and protein expression
      levels of NOS-2 in HCC were also significantly lower compared to adjacent non
      tumor liver tissues (P<0.01 for both). We found that the levels of NO in patients
      suffering from HCC metastasis were lower compared to those without metastasis
      (P<0.05) and NOS-2 expression was correlated with tumor diameter (P<0.05) and
      metastasis (P<0.05). In addition, mutant p53 protein was expressed in the
      majority of HCC samples and the proliferation rate of HCC was significantly
      higher than that of adjacent non-tumor liver tissues. These data indicate that
      decreased levels of NO/NOS-2 may partially contribute to overexpression of the
      mutant p53 protein and excessive proliferation; this may be a potential mechanism
      in the development and progression of HCC.

PMID- 23007409
TI  - Gemcitabine reactivates epigenetically silenced genes and functions as a DNA
      methyltransferase inhibitor.
AB  - Gemcitabine is indicated in combination with cisplatin as first-line therapy for
      solid tumours including non-small cell lung cancer (NSCLC), bladder cancer and
      mesothelioma. Gemcitabine is an analogue of pyrimidine cytosine and functions as
      an anti-metabolite. Structurally, however, gemcitabine has similarities to 5-aza
      2-deoxycytidine (decitabine/Dacogen(r)), a DNA methyltransferase inhibitor
      (DNMTi). NSCLC, mesothelioma and prostate cancer cell lines were treated with
      decitabine and gemcitabine. Reactivation of epigenetically silenced genes was
      examined by RT-PCR/qPCR. DNA methyltransferase activity in nuclear extracts and
      recombinant proteins was measured using a DNA methyl-transferase assay, and
      alterations in DNA methylation status were examined using methylation-specific
      PCR (MS-PCR) and pyrosequencing. We observe a reactivation of several
      epigenetically silenced genes including GSTP1, IGFBP3 and RASSF1A. Gemcitabine
      functionally inhibited DNA methyltransferase activity in both nuclear extracts
      and recombinant proteins. Gemcitabine dramatically destabilised DNMT1 protein.
      However, DNA CpG methylation was for the most part unaffected by gemcitabine. In
      conclusion, gemcitabine both inhibits and destabilises DNA methyltransferases and
      reactivates epigenetically silenced genes having activity equivalent to
      decitabine at concentrations significantly lower than those achieved in the
      treatment of patients with solid tumours. This property may contribute to the
      anticancer activity of gemcitabine.

PMID- 23007410
TI  - Planarian immobilization, partial irradiation, and tissue transplantation.
AB  - The planarian, a freshwater flatworm, has proven to be a powerful system for
      dissecting metazoan regeneration and stem cell biology. Planarian regeneration of
      any missing or damaged tissues is made possible by adult stem cells termed
      neoblasts. Although these stem cells have been definitively shown to be
      pluripotent and singularly capable of reconstituting an entire animal, the
      heterogeneity within the stem cell population and the dynamics of their cellular
      behaviors remain largely unresolved. Due to the large number and wide
      distribution of stem cells throughout the planarian body plan, advanced methods
      for manipulating subpopulations of stem cells for molecular and functional study
      in vivo are needed. Tissue transplantation and partial irradiation are two
      methods by which a subpopulation of planarian stem cells can be isolated for
      further study. Each technique has distinct advantages. Tissue transplantation
      allows for the introduction of stem cells, into a naive host, that are either
      inherently genetically distinct or have been previously treated
      pharmacologically. Alternatively, partial irradiation allows for the isolation of
      stem cells within a host, juxtaposed to tissue devoid of stem cells, without the
      introduction of a wound or any breech in tissue integrity. Using these two
      methods, one can investigate the cell autonomous and non-autonomous factors that
      control stem cell functions, such as proliferation, differentiation, and
      migration. Both tissue transplantation and partial irradiation have been used
      historically in defining many of the questions about planarian regeneration that
      remain under study today. However, these techniques have remained underused due
      to the laborious and inconsistent nature of previous methods. The protocols
      presented here represent a large step forward in decreasing the time and effort
      necessary to reproducibly generate large numbers of grafted or partially
      irradiated animals with efficacies approaching 100 percent. We cover the culture
      of large animals, immobilization, preparation for partial irradiation, tissue
      transplantation, and the optimization of animal recovery. Furthermore, the work
      described here demonstrates the first application of the partial irradiation
      method for use with the most widely studied planarian, Schmidtea mediterranea.
      Additionally, efficient tissue grafting in planaria opens the door for the
      functional testing of subpopulations of naive or treated stem cells in
      repopulation assays, which has long been the gold-standard method of assaying
      adult stem cell potential in mammals. Broad adoption of these techniques will no
      doubt lead to a better understanding of the cellular behaviors of adult stem
      cells during tissue homeostasis and regeneration.

PMID- 23007411
TI  - Foot drop secondary to peroneal intraneural cyst arising from tibiofibular joint.
AB  - An 11-year-old boy presented to our outpatient clinic with a three-month history
      of pain over the fibular head area and gait difficulty. Surgical exploration
      revealed a mass arising from the superior tibiofibular joint invading the
      peroneal nerve along the articular branch of the common peroneal nerve. The
      pathogenesis of the intraneural ganglion of the peroneal nerve may be an
      articular origin and superior tibiofibular joint is the central point. LEVEL OF
      EVIDENCE: V.

PMID- 23007412
TI  - Fixed- versus mobile-bearing unicondylar knee arthroplasty: are failure modes
      different?
AB  - PURPOSE: An ongoing controversy exists on whether mobile-bearing design is
      superior over fixed-bearing design in unicondylar knee arthroplasties (UKAs). The
      present study conducted a systematic review to ascertain differences in
      performance between fixed- and mobile-bearing designs in UKAs. METHODS: A
      literature search was performed in PubMed, Embase, Scopus and the Cochrane
      Library. A total of 9 comparative studies involving 915 knees comparing outcomes
      of mobile-bearing UKAs with fixed-bearing UKAs were included in the current
      analysis. Outcomes of interest included knee function, quality of life,
      radiographic outcomes, reasons and incidence of reoperation, timing of failures,
      and survivorship. RESULTS: The results presented no significant differences
      between the two designs in terms of knee scores, range of motion, limb alignment,
      implant positioning, incidence of radiolucent lines and overall reoperation
      rates. However, their differences have been noted in their modes and timing of
      failures. Early failures are related to the risk of bearing dislocation in the
      mobile-bearing design. In contrast, later failures are related to the risk of
      polyethylene wear in the fixed-bearing design. CONCLUSIONS: The available
      evidence has not confirmed the advantage of mobile-bearing UKAs over fixed
      bearing UKAs but pointed out specific modes of failure.

PMID- 23007413
TI  - Outcomes for primary anterior cruciate reconstruction with the quadriceps
      autograft: a systematic review.
AB  - PURPOSE: To determine the suitability of the quadriceps autograft in primary
      anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic review was
      undertaken to identify all clinical studies reporting on the use of the
      quadriceps tendon autograft in ACL reconstructions. Studies that reported on
      clinical and functional outcomes, morbidity and complications were selected.
      RESULTS: Seventeen articles met our inclusion criteria with a total of 1,580
      reconstructions studied. This included four comparative studies which compared
      the quadriceps tendon to either hamstring or patella tendon autografts. The
      quadriceps tendon autograft had clinical (Lachman, Pivot-shift testing) and
      functional outcomes (Lysholm and IKDC scores) similar to those reported for the
      patella tendon and hamstring grafts in the literature. Comparative studies also
      reported no significant difference between the grafts for any outcome measure.
      CONCLUSIONS: The quadriceps tendon autograft is a promising alternative for
      primary ACL reconstructions with good outcomes and minimal donor site morbidity.
      Further studies are required, however, to determine whether the quadriceps graft
      is as good as or better than other autografts. LEVEL OF EVIDENCE: IV.

PMID- 23007414
TI  - Faster quadriceps recovery with the far medial subvastus approach in minimally
      invasive total knee arthroplasty.
AB  - PURPOSE: To identify whether less proximal muscle damage during minimally
      invasive surgery will allow faster recovery after total knee arthroplasty in
      comparison with a quadriceps incision approach. A limited medial parapatellar
      approach without tibial medial collateral ligament (MCL) release was compared to
      a subvastus approach without tibial medial collateral ligament release (far
      medial subvastus). METHODS: One hundred and eighty patients were studied. In the
      mini-parapatellar group, ninety patients and in the far medial subvastus group,
      the remaining ninety patients were included. The evaluation was based on the Knee
      Society Score, VAS, morphine consumption, range of motion, time to straight leg
      raising, walking without aid, stairs and period of hospitalization. Alignment on
      full leg radiographs and component position on plain films were measured.
      RESULTS: The far medial subvastus group showed faster recovery with earlier
      straight leg raising (1.7 +/- 0.5 vs. 2.7 +/- 0.4 days), postoperative weight
      bearing without aid (1.7 +/- 0.6 vs. 2 +/- 0.8 days) and stair negotiation (3 +/-
      0.4 vs. 4 +/- 0.3 days) resulting in shorter length of stay (4 +/- 0.5 vs. 5 +/-
      1.2 days). Comparable Knee Society Scores (88.5 +/- 6.8 vs. 90 +/- 10), Function
      Scores (90 +/- 10) and alignment (5.4 degrees  +/- 2.1 degrees  vs. 5.0 degrees 
      +/- 2.4 degrees ) between the medial parapatellar and far medial subvastus group
      were observed at a follow-up of 24 months. An increase in operative time for the
      far medial subvastus was observed (55 +/- 10.6 min vs. 67 +/- 12 min tourniquet
      time) but without complications. CONCLUSION: The MCL sparing far medial subvastus
      approach allows good surgical exposure, faster straight leg raising, full weight
      bearing without aid and shorter length of stay with most importantly no
      radiological malalignment. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 23007415
TI  - The juxtamembrane domain of the E-cadherin cytoplasmic tail contributes to its
      interaction with Myosin VI.
AB  - We recently identified the atypical myosin, Myosin VI, as a component of
      epithelial cell-cell junctions that interacts with E-cadherin. Recombinant
      proteins bearing the cargo-binding domain of Myosin VI (Myo VI-CBD) or the
      cytoplasmic tail of E-cadherin can interact directly with one another. In this
      report we further investigate the molecular requirements of the interaction
      between Myo VI-CBD and E-cadherin combining truncation mutation analysis with in
      vitro binding assays. We report that a short (28 amino acid) juxtamembrane region
      of the cadherin cytoplasmic tail is sufficient to bind Myo VI-CBD. However,
      central regions of the cadherin tail adjacent to the juxtamembrane sequence also
      display binding activity for Myo VI-CBD. It is therefore possible that the
      cadherin tail bears two binding sites for Myosin VI, or an extended binding site
      that includes the juxtamembrane region. Nevertheless, our biochemical data
      highlight the capacity for the juxtamembrane region to interact with functionally
      significant cytoplasmic proteins. 

PMID- 23007416
TI  - Minor anomalies in childhood lymphomas and solid tumors.
AB  - BACKGROUND: Despite the presence of reports on correlation between major
      congenital defects and cancer, very few studies have investigated the frequency
      of minor anomalies in childhood malignancy. The aim of this study was to
      determine the prevalence of minor anomalies in children with lymphoma and solid
      tumors. PROCEDURE: A total of 281 well-defined minor anomalies were determined in
      116 patients. The patients were compared with age-matched and sex-matched healthy
      control subjects. RESULTS: Concerning the cumulative data, 87.9% (102/116) of the
      patients and 37.9% (44/116) of the controls had at least 1 minor anomaly (P <
      0.05). A total of 281 minor anomalies (2.42 per subject) were noted in the
      patient group, whereas 41 (0.35 per subject) were noted in the control group (P <
      0.05). The eye, ear, mouth, hand, and feet anomalies were statistically higher in
      the patient group than the control group (P < 0.05). CONCLUSIONS: Our results
      contribute to the understanding of the role of genetic factors in childhood
      cancer. Future studies might be directed toward identifying the developmental
      pathways and the relevant genes that are involved in relation to childhood cancer
      and minor anomalies.

PMID- 23007417
TI  - Coexistence of beta-thalassemia trait and hemochromatosis in a 5-year-old girl of
      Polish origin.

PMID- 23007418
TI  - Life-threatening agranulocytosis, anemia, and plasmacytosis after dipyrone use
      for fever in a child.
AB  - Dipyrone or metamizole Na (Novalgin) is commonly used as an antipyretic,
      analgesic, and spasmolytic agent in some parts of the world; however, it is
      banned in developed countries because of severe side effects. Here we present a
      case of a 4-year-old boy who developed life-threatening agranulocytosis, anemia,
      and marked plasmacytosis in his bone marrow after dipyrone use for fever, which
      resolved with steroid therapy. 

PMID- 23007419
TI  - Prominent megakaryocytic dysplasia after regression of transient abnormal
      myelopoiesis associated with GATA-1 mutation.
AB  - About a quarter of children with Down syndrome and transient abnormal
      myelopoiesis (TAM) progress to acute megakaryoblastic leukemia (AMKL). We
      describe isolated dysmegakaryopoiesis despite complete resolution of TAM in an 18
      month-old girl, who developed AMKL 6 months later.

PMID- 23007420
TI  - Pulmonary nodules with central cavitation in a young child.
AB  - Autopsy findings of a young boy presenting with high-grade fever,cough, and
      respiratory distress and with a family history of tuberculosis are described.

PMID- 23007421
TI  - Supporting rural family palliative caregivers.
AB  - There is urgent need to effectively support the well-being of rural palliative
      family caregivers (FCGs). A mixed method study was conducted with 23 FCGs. Data
      collection included completion of an assessment questionnaire and semistructured
      interviews. The most prevalent needs identified by questionnaire were caring for
      the patient's pain, fatigue, body, and nourishment; FCG's fatigue and need for
      respite. Yet few FCGs wanted more attention to these needs by healthcare
      providers. FCGs resisted considering their own personal needs. Instead, they
      focused on needs related to providing care including to be(come) a palliative
      caregiver, be skilled and know more, navigate competing wishes, needs, demands,
      and priorities, and for "an extra pair of hands." Gaps in rural palliative
      services contributed to low expectations for assistance; reluctance to seek
      assistance was influenced by FCGs' resourcefulness and independence. Findings
      suggest that supporting FCGs will most likely be successful when framed in
      relation to their caregiving role.

PMID- 23007422
TI  - African American caregiving grandmothers: results of an intervention to improve
      health indicators and health promotion behaviors.
AB  - The purpose of this study was to examine the efficacy of an intervention to
      improve the health of grandmothers raising grandchildren. A pre- and post-test
      design was employed with 504 African American grandmother participants. The
      intervention included monthly home-based visitation by registered nurses (RNs)
      and social workers, participation in support groups and parenting classes,
      referrals for legal services, and early intervention services for children with
      special needs. The Health Risk Appraisal was used to assess health indicators and
      health promotion behaviors. A comparison of pre- and post-test scores indicated
      significant (p < .002) changes in the desired direction for a number of health
      indicators and health promotion behaviors, including blood pressure, annual
      routine cancer screenings, frequency of weekly exercise, and improved dietary
      intake, as well as participants' perception of their health and life
      satisfaction. No improvements were observed in the proportion of participants who
      were obese or overweight.

PMID- 23007423
TI  - What is computational toxicology?
AB  - Computational toxicology is a vibrant and rapidly developing discipline that
      integrates information and data from a variety of sources to develop mathematical
      and computer-based models to better understand and predict adverse health effects
      caused by chemicals, such as environmental pollutants and pharmaceuticals.
      Encompassing medicine, biology, biochemistry, chemistry, mathematics, computer
      science, engineering, and other fields, computational toxicology investigates the
      interactions of chemical agents and biological organisms across many scales
      (e.g., population, individual, cellular, and molecular). This multidisciplinary
      field has applications ranging from hazard and risk prioritization of chemicals
      to safety screening of drug metabolites, and has active participation and growth
      from many organizations, including government agencies, not-for-profit
      organizations, private industry, and universities.

PMID- 23007424
TI  - Computational toxicology: application in environmental chemicals.
AB  - This chapter provides an overview of computational models that describe various
      aspects of the source-to-health effect continuum. Fate and transport models
      describe the release, transportation, and transformation of chemicals from
      sources of emission throughout the general environment. Exposure models integrate
      the microenvironmental concentrations with the amount of time an individual
      spends in these microenvironments to estimate the intensity, frequency, and
      duration of contact with environmental chemicals. Physiologically based
      pharmacokinetic (PBPK) models incorporate mechanistic biological information to
      predict chemical-specific absorption, distribution, metabolism, and excretion.
      Values of parameters in PBPK models can be measured in vitro, in vivo, or
      estimated using computational molecular modeling. Computational modeling is also
      used to predict the respiratory tract dosimetry of inhaled gases and particulates
      [computational fluid dynamics (CFD) models], to describe the normal and
      xenobiotic-perturbed behaviors of signaling pathways, and to analyze the growth
      kinetics of preneoplastic lesions and predict tumor incidence (clonal growth
      models).

PMID- 23007425
TI  - Role of computational methods in pharmaceutical sciences.
AB  - Over the past two decades computational methods have eased up the financial and
      experimental burden of early drug discovery process. The in silico methods have
      provided support in terms of databases, data mining of large genomes, network
      analysis, systems biology on the bioinformatics front and structure-activity
      relationship, similarity analysis, docking, and pharmacophore methods for lead
      design and optimization. This review highlights some of the applications of
      bioinformatics and chemoinformatics methods that have enriched the field of drug
      discovery. In addition, the review also provided insights into the use of free
      energy perturbation methods for efficiently computing binding energy. These in
      silico methods are complementary and can be easily integrated into the
      traditional in vitro and in vivo methods to test pharmacological hypothesis.

PMID- 23007426
TI  - Best practices in mathematical modeling.
AB  - Mathematical modeling is a vehicle that allows for explanation and prediction of
      natural phenomena. In this chapter we present guidelines and best practices for
      developing and implementing mathematical models, using cancer growth,
      chemotherapy, and immunotherapy modeling as examples.

PMID- 23007427
TI  - Tools and techniques.
AB  - This chapter lists some of the software and tools that are used in computational
      toxicology, as presented in this volume.

PMID- 23007428
TI  - Prediction of physicochemical properties.
AB  - Physicochemical properties are key factors in controlling the interactions of
      xenobiotics with living organisms. Computational approaches to toxicity
      prediction therefore generally rely to a very large extent on the physicochemical
      properties of the query compounds. Consequently it is important that reliable in
      silico methods are available for the rapid calculation of physicochemical
      properties. The key properties are partition coefficient, aqueous solubility, and
      pKa and, to a lesser extent, melting point, boiling point, vapor pressure, and
      Henry's law constant (air-water partition coefficient). The calculation of each
      of these properties from quantitative structure-property relationships (QSPRs)
      and from available software is discussed in detail, and recommendations made.
      Finally, detailed consideration is given of guidelines for the development of
      QSPRs and QSARs.

PMID- 23007429
TI  - Informing mechanistic toxicology with computational molecular models.
AB  - Computational molecular models of chemicals interacting with biomolecular targets
      provides toxicologists a valuable, affordable, and sustainable source of in
      silico molecular level information that augments, enriches, and complements in
      vitro and in vivo efforts. From a molecular biophysical ansatz, we describe how
      3D molecular modeling methods used to numerically evaluate the classical pair
      wise potential at the chemical/biological interface can inform mechanism of
      action and the dose-response paradigm of modern toxicology. With an emphasis on
      molecular docking, 3D-QSAR and pharmacophore/toxicophore approaches, we
      demonstrate how these methods can be integrated with chemoinformatic and
      toxicogenomic efforts into a tiered computational toxicology workflow. We
      describe generalized protocols in which 3D computational molecular modeling is
      used to enhance our ability to predict and model the most relevant toxicokinetic,
      metabolic, and molecular toxicological endpoints, thereby accelerating the
      computational toxicology-driven basis of modern risk assessment while providing a
      starting point for rational sustainable molecular design.

PMID- 23007430
TI  - Chemical structure representations and applications in computational toxicity.
AB  - Efficient storage and retrieval of chemical structures is one of the most
      important prerequisite for solving any computational-based problem in life
      sciences. Several resources including research publications, text books, and
      articles are available on chemical structure representation. Chemical substances
      that have same molecular formula but several structural formulae, conformations,
      and skeleton framework/scaffold/functional groups of the molecule convey various
      characteristics of the molecule. Today with the aid of sophisticated mathematical
      models and informatics tools, it is possible to design a molecule of interest
      with specified characteristics based on their applications in pharmaceuticals,
      agrochemicals, biotechnology, nanomaterials, petrochemicals, and polymers. This
      chapter discusses both traditional and current state of art representation of
      chemical structures and their applications in chemical information management,
      bioactivity- and toxicity-based predictive studies.

PMID- 23007431
TI  - Accessing and using chemical property databases.
AB  - Chemical compounds participate in all the processes of life. Understanding the
      complex interactions of small molecules such as metabolites and drugs and the
      biological macromolecules that consume and produce them is key to gaining a wider
      understanding in a systemic context. Chemical property databases collect
      information on the biological effects and physicochemical properties of chemical
      entities. Accessing and using such databases is key to understanding the
      chemistry of toxic molecules. In this chapter, we present methods to search,
      understand, download, and manipulate the wealth of information available in
      public chemical property databases, with particular focus on the database of
      Chemical Entities of Biological Interest (ChEBI).

PMID- 23007432
TI  - Accessing, using, and creating chemical property databases for computational
      toxicology modeling.
AB  - Toxicity data is expensive to generate, is increasingly seen as precompetitive,
      and is frequently used for the generation of computational models in a discipline
      known as computational toxicology. Repositories of chemical property data are
      valuable for supporting computational toxicologists by providing access to data
      regarding potential toxicity issues with compounds as well as for the purpose of
      building structure-toxicity relationships and associated prediction models. These
      relationships use mathematical, statistical, and modeling computational
      approaches and can be used to understand the mechanisms by which chemicals cause
      harm and, ultimately, enable prediction of adverse effects of these chemicals to
      human health and/or the environment. Such approaches are of value as they offer
      an opportunity to prioritize chemicals for testing. An increasing amount of data
      used by computational toxicologists is being published into the public domain
      and, in parallel, there is a greater availability of Open Source software for the
      generation of computational models. This chapter provides an overview of the
      types of data and software available and how these may be used to produce
      predictive toxicology models for the community.

PMID- 23007433
TI  - Molecular dynamics.
AB  - Molecular dynamics (MD) simulation holds the promise of revealing the mechanisms
      of biological processes in their ultimate detail. It is carried out by computing
      the interaction forces acting on each atom and then propagating the velocities
      and positions of the atoms by numerical integration of Newton's equations of
      motion. In this review, we present an overview of how the MD simulation can be
      conducted to address computational toxicity problems. The study cases will cover
      a standard MD simulation performed to investigate the overall flexibility of a
      cytochrome P450 (CYP) enzyme and a set of more advanced MD simulations to examine
      the barrier to ion conduction in a human alpha7 nicotinic acetylcholine receptor
      (nAChR).

PMID- 23007434
TI  - Introduction to pharmacokinetics in clinical toxicology.
AB  - In clinical toxicology, a better understanding of the pharmacokinetics of the
      drugs may be useful in both risk assessment and formulating treatment guidelines
      for patients. Pharmacokinetics describes the time course of drug concentrations
      and is a driver for the time course of drug effects. In this chapter
      pharmacokinetics is described from a mathematical modeling perspective as applied
      to clinical toxicology. The pharmacokinetics of drugs are described using a
      combination of input and disposition (distribution and elimination) phases. A
      description of the time course of the input and disposition of drugs in overdose
      provides a basis for understanding the time course of effects of drugs in
      overdose. Relevant clinical toxicology examples are provided to explain various
      pharmacokinetic principles. Throughout this chapter we have taken a pragmatic
      approach to understanding and interpreting the time course of drug effects.

PMID- 23007435
TI  - Modeling of absorption.
AB  - Absorption takes place when a compound enters an organism, which occurs as soon
      as the molecules enter the first cellular bilayer(s) in the tissue(s) to which is
      it exposed. At that point, the compound is no longer part of the environment
      (which includes the alimentary canal for oral exposure), but has become part of
      the organism. If absorption is prevented or limited, then toxicological effects
      are also prevented or limited. Thus, modeling absorption is the first step in
      simulating/predicting potential toxicological effects. Simulation software used
      to model absorption of compounds of various types has advanced considerably over
      the past 15 years. There can be strong interactions between absorption and
      pharmacokinetics (PK), requiring state-of-the-art simulation computer programs
      that combine absorption with either compartmental pharmacokinetics (PK) or
      physiologically based pharmacokinetics (PBPK). Pharmacodynamic (PD) models for
      therapeutic and adverse effects are also often linked to the absorption and PK
      simulations, providing PK/PD or PBPK/PD capabilities in a single package. These
      programs simulate the interactions among a variety of factors including the
      physicochemical properties of the molecule of interest, the physiologies of the
      organisms, and in some cases, environmental factors, to produce estimates of the
      time course of absorption and disposition of both toxic and nontoxic substances,
      as well as their pharmacodynamic effects.

PMID- 23007436
TI  - Prediction of pharmacokinetic parameters.
AB  - In silico tools specifically developed for prediction of pharmacokinetic
      parameters are of particular interest to pharmaceutical industry because of the
      high potential of discarding inappropriate molecules during an early stage of
      drug development itself with consequent saving of vital resources and valuable
      time. The ultimate goal of the in silico models of absorption, distribution,
      metabolism, and excretion (ADME) properties is the accurate prediction of the in
      vivo pharmacokinetics of a potential drug molecule in man, whilst it exists only
      as a virtual structure. Various types of in silico models developed for
      successful prediction of the ADME parameters like oral absorption,
      bioavailability, plasma protein binding, tissue distribution, clearance, half
      life, etc. have been briefly described in this chapter.

PMID- 23007437
TI  - Ligand- and structure-based pregnane X receptor models.
AB  - The human pregnane X receptor (PXR) is a ligand dependent transcription factor
      that can be activated by structurally diverse agonists including steroid
      hormones, bile acids, herbal drugs, and prescription medications. PXR regulates
      the transcription of several genes involved in xenobiotic detoxification and
      apoptosis. Activation of PXR has the potential to initiate adverse effects by
      altering drug pharmacokinetics or perturbing physiological processes. Hence, more
      reliable prediction of PXR activators would be valuable for pharmaceutical drug
      discovery to avoid potential toxic effects. Ligand- and protein structure-based
      computational models for PXR activation have been developed in several studies.
      There has been limited success with structure-based modeling approaches to
      predict human PXR activators, which can be attributed to the large and
      promiscuous site of this protein. Slightly better success has been achieved with
      ligand-based modeling methods including quantitative structure-activity
      relationship (QSAR) analysis, pharmacophore modeling and machine learning that
      use appropriate descriptors to account for the diversity of the ligand classes
      that bind to PXR. These combined computational approaches using molecular shape
      information may assist scientists to more confidently identify PXR activators.
      This chapter reviews the various ligand and structure based methods undertaken to
      date and their results.

PMID- 23007438
TI  - Non-compartmental analysis.
AB  - When analyzing pharmacokinetic data, one generally employs either model fitting
      using nonlinear regression analysis or non-compartmental analysis techniques
      (NCA). The method one actually employs depends on what is required from the
      analysis. If the primary requirement is to determine the degree of exposure
      following administration of a drug (such as AUC), and perhaps the drug's
      associated pharmacokinetic parameters, such as clearance, elimination half-life,
      T (max), C (max), etc., then NCA is generally the preferred methodology to use in
      that it requires fewer assumptions than model-based approaches. In this chapter
      we cover NCA methodologies, which utilize application of the trapezoidal rule for
      measurements of the area under the plasma concentration-time curve. This method,
      which generally applies to first-order (linear) models (although it is often used
      to assess if a drug's pharmacokinetics are nonlinear when several dose levels are
      administered), has few underlying assumptions and can readily be automated.In
      addition, because sparse data sampling methods are often utilized in
      toxicokinetic (TK) studies, NCA methodology appropriate for sparse data is also
      discussed.

PMID- 23007439
TI  - Compartmental modeling in the analysis of biological systems.
AB  - Compartmental models are composed of sets of interconnected mixing chambers or
      stirred tanks. Each component of the system is considered to be homogeneous,
      instantly mixed, with uniform concentration. The state variables are
      concentrations or molar amounts of chemical species. Chemical reactions,
      transmembrane transport, and binding processes, determined in reality by
      electrochemical driving forces and constrained by thermodynamic laws, are
      generally treated using first-order rate equations. This fundamental simplicity
      makes them easy to compute since ordinary differential equations (ODEs) are
      readily solved numerically and often analytically. While compartmental systems
      have a reputation for being merely descriptive they can be developed to levels
      providing realistic mechanistic features through refining the kinetics.
      Generally, one is considering multi-compartmental systems for realistic modeling.
      Compartments can be used as "black" box operators without explicit internal
      structure, but in pharmacokinetics compartments are considered as homogeneous
      pools of particular solutes, with inputs and outputs defined as flows or solute
      fluxes, and transformations expressed as rate equations.Descriptive models
      providing no explanation of mechanism are nevertheless useful in modeling of many
      systems. In pharmacokinetics (PK), compartmental models are in widespread use for
      describing the concentration-time curves of a drug concentration following
      administration. This gives a description of how long it remains available in the
      body, and is a guide to defining dosage regimens, method of delivery, and
      expectations for its effects. Pharmacodynamics (PD) requires more depth since it
      focuses on the physiological response to the drug or toxin, and therefore
      stimulates a demand to understand how the drug works on the biological system;
      having to understand drug response mechanisms then folds back on the delivery
      mechanism (the PK part) since PK and PD are going on simultaneously (PKPD).Many
      systems have been developed over the years to aid in modeling PKPD systems.
      Almost all have solved only ODEs, while allowing considerable conceptual
      complexity in the descriptions of chemical transformations, methods of solving
      the equations, displaying results, and analyzing systems behavior. Systems for
      compartmental analysis include Simulation and Applied Mathematics, CoPasi
      (enzymatic reactions), Berkeley Madonna (physiological systems), XPPaut
      (dynamical system behavioral analysis), and a good many others. JSim, a system
      allowing the use of both ODEs and partial differential equations (that describe
      spatial distributions), is used here. It is an open source system, meaning that
      it is available for free and can be modified by users. It offers a set of
      features unique in breadth of capability that make model verification surer and
      easier, and produces models that can be shared on all standard computer
      platforms.

PMID- 23007440
TI  - Physiologically based pharmacokinetic/toxicokinetic modeling.
AB  - Physiologically based pharmacokinetic (PBPK) models differ from conventional
      compartmental pharmacokinetic models in that they are based to a large extent on
      the actual physiology of the organism. The application of pharmacokinetics to
      toxicology or risk assessment requires that the toxic effects in a particular
      tissue are related in some way to the concentration time course of an active form
      of the substance in that tissue. The motivation for applying pharmacokinetics is
      the expectation that the observed effects of a chemical will be more simply and
      directly related to a measure of target tissue exposure than to a measure of
      administered dose. The goal of this work is to provide the reader with an
      understanding of PBPK modeling and its utility as well as the procedures used in
      the development and implementation of a model to chemical safety assessment using
      the styrene PBPK model as an example.

PMID- 23007441
TI  - Interspecies extrapolation.
AB  - Interspecies extrapolation encompasses two related but distinct topic areas that
      are germane to quantitative extrapolation and hence computational toxicology-dose
      scaling and parameter scaling. Dose scaling is the process of converting a dose
      determined in an experimental animal to a toxicologically equivalent dose in
      humans using simple allometric assumptions and equations. In a hierarchy of
      quantitative extrapolation approaches, this option is used when minimal
      information is available for a chemical of interest. Parameter scaling refers to
      cross-species extrapolation of specific biological processes describing rates
      associated with pharmacokinetic (PK) or pharmacodynamic (PD) events on the basis
      of allometric relationships. These parameters are used in biologically based
      models of various types that are designed for not only cross-species
      extrapolation but also for exposure route (e.g., inhalation to oral) and exposure
      scenario (duration) extrapolation. This area also encompasses in vivo scale-up of
      physiological rates determined in various experimental systems. Results from in
      vitro metabolism studies are generally most useful for interspecies extrapolation
      purposes when integrated into a physiologically based pharmacokinetic (PBPK)
      modeling framework. This is because PBPK models allow consideration and
      quantitative evaluation of other physiological factors, such as binding to plasma
      proteins and blood flow to the liver, which may be as or more influential than
      metabolism in determining relevant dose metrics for risk assessment.

PMID- 23007442
TI  - Population effects and variability.
AB  - Chemical risk assessment for human health requires a multidisciplinary approach
      through four steps: hazard identification and characterization, exposure
      assessment, and risk characterization. Hazard identification and characterization
      aim to identify the metabolism and elimination of the chemical (toxicokinetics)
      and the toxicological dose-response (toxicodynamics) and to derive a health-based
      guidance value for safe levels of exposure. Exposure assessment estimates human
      exposure as the product of the amount of the chemical in the matrix consumed and
      the consumption itself. Finally, risk characterization evaluates the risk of the
      exposure to human health by comparing the latter to with the health-based
      guidance value. Recently, many research efforts in computational toxicology have
      been put together to characterize population variability and uncertainty in each
      of the steps of risk assessment to move towards more quantitative and transparent
      risk assessment. This chapter focuses specifically on modeling population
      variability and effects for each step of risk assessment in order to provide an
      overview of the statistical and computational tools available to toxicologists
      and risk assessors. Three examples are given to illustrate the applicability of
      those tools: derivation of pathway-related uncertainty factors based on
      population variability, exposure to dioxins, dose-response modeling of cadmium.

PMID- 23007444
TI  - The yeast hypoxic responses, resources for new biotechnological opportunities.
AB  - Recent advances in the knowledge of molecular mechanisms that control the
      adaptation to low oxygen levels in yeast and their biotechnological applications,
      including bioproduct synthesis, such as ethanol, glutathione or recombinant
      proteins, as well as pathogenic virulence, are reviewed. Possible pathways and
      target genes, which might be of particular interest for the improvement of
      biotechnological applications, are evaluated.

PMID- 23007443
TI  - Mechanism-based pharmacodynamic modeling.
AB  - Pharmacodynamic modeling is based on a quantitative integration of
      pharmacokinetics, pharmacological systems, and (patho-) physiological processes
      for understanding the intensity and time-course of drug effects on the body.
      Application of such models to the analysis of meaningful experimental data allows
      for the quantification and prediction of drug-system interactions for both
      therapeutic and adverse drug responses. In this chapter, commonly used
      mechanistic pharmacodynamic models are presented with respect to their important
      features, operable equations, and signature profiles. In addition, literature
      examples showcasing the utility of these models to adverse drug events are
      highlighted. Common model types that are covered include simple direct effects,
      biophase distribution, indirect effects, signal transduction, and irreversible
      effects.

PMID- 23007445
TI  - In vitro immunomodulatory properties of osteogenic and adipogenic differentiated
      mesenchymal stem cells isolated from three inbred mouse strains.
AB  - Mesenchymal stem cells (MSCs) are used for cell-based therapies because of their
      immunomodulatory properties. The immunomodulatory properties of adipogenic (AD)
      and osteogenic (OS) differentiated adipose tissue-derived MSCs (AD-MSCs) isolated
      from BALB/c, C57BL/6, and DBA mice were compared. Splenocytes proliferation was
      suppressed in the presence of AD-MSCs conditioned media in all mice. After OS
      differentiation, BALB/c AD-MSCs produced higher levels of TGF-beta and IL-17 and
      lower levels of NO than AD-MSCs isolated from C57BL/6 and DBA mice. In addition,
      OS differentiated AD-MSCs isolated from DBA mice produced lower levels of IL-10
      than AD-MSCs isolated from C57BL/6 and DBA mice. After in vitro AD and OD
      differentiation, AD-MSCs isolated from each mouse produced higher levels of NO
      and IDO than undifferentiated cells. Additionally, AD-MSCs isolated from C57BL/6
      and DBA mice produced higher levels of NO than AD-MSCs isolated from BALB/c mice.
      Adipose tissue-derived MSCs thus retain their immunomodulatory properties after
      in vitro OS and AD differentiation in a strain-dependent manner.

PMID- 23007446
TI  - Multiparameter flow cytometry for the characterization of human embryonic stem
      cells.
AB  - Using multiparameter staining methods and flow cytometry to investigate the
      pluripotency of HUES7 human embryonic stem cell cultures, it was found that the
      multidimensional approach of marker co-expression allowed the different cell
      populations to be easily identified and demonstrated cross reactivity between the
      SSEA 4 and SSEA 1 antibodies, resulting in a substantial false positive SSEA 1
      population. It is the accepted norm to apply control gates at a 95 % confidence
      level of the isotype control; however, this study found that adjusting the
      control gate to a 99 % confidence level significantly reduced the effect of this
      cross reactivity. Though conversely, this gating shift also decreased the
      positive marker expression of SSEA 4 and Tra-1-60, indicating that there is a
      need for strongly expressing markers coupled with increased optimization of
      fluorophore/antibody combinations before a gating strategy of 99 % can be
      implemented on a more routine basis.

PMID- 23007447
TI  - Overexpression of rice LRK1 restricts internode elongation by down-regulating
      OsKO2.
AB  - Rice (Oryza sativa) has the potential to undergo rapid internodal elongation
      which determines plant height. Gibberellin is involved in internode elongation.
      Leucine-rich repeat receptor-like kinases (LRR-RLKs) are the largest subfamily of
      transmembrane receptor-like kinases in plants. LRR-RLKs play important functions
      in mediating a variety of cellular processes and regulating responses to
      environmental signals. LRK1, a PSK receptor homolog, is a member of the LRR-RLK
      family. In the present study, differences in ectopic expression of LRK1 were
      consistent with extent of rice internode elongation. Analyses of gene expression
      demonstrated that LRK1 restricts gibberellin biosynthesis during the internode
      elongation process by down-regulation of the gibberellin biosynthetic gene coding
      for ent-kaurene oxidase.

PMID- 23007448
TI  - Genetic manipulation revealing an unusual N-terminal region in a stand-alone non
      ribosomal peptide synthetase involved in the biosynthesis of ramoplanins.
AB  - Ramoplanins produced by Actinoplanes are new structural class of lipopeptide and
      are currently in phase III clinical trials for the prevention of vancomycin
      resistant enterococcal infections. The depsipeptide structures of ramoplanins are
      synthesized by non-ribosomal peptide synthetases (NRPS). Romo-orf17, a stand
      alone NRPS, is responsible for the recruitment of Thr into the linear NRPS
      pathways for which the corresponding adenylation domain is absent. Here,
      systematical gene inactivation and complementation have been carried out in a
      Actinoplanes sp. using homologous recombination and site-specific integration
      methods. A hybrid gene coding for the N-terminal region of the stand-alone NRPS
      and the A-PCP domains of a heterologous NRPS restored production of ramoplanins.
      The results elucidate the unusual N-terminal region which is essential for the
      biosynthesis of ramoplanins.

PMID- 23007449
TI  - Growth and positioning of adipose-derived stem cells in microfluidic devices.
AB  - Stem cells hold great promise for treatment of various degenerative diseases.
      However, clinical studies have only shown very moderate benefits of cell therapy.
      We believe that insufficiency of therapeutic benefits is due to limited homing of
      implanted stem cells to targeted organs. Microfluidic devices are a very useful
      research tool for quantitative characterizations of stem cells. The present study
      therefore was to assess the effects of epidermal growth factor (EGF) and direct
      current electric field (dcEF) on the growth and trafficking of adipose-derived
      stem cells (ASC). It was found that EGF did not affect cell proliferation in cell
      culture flasks. However, ASC proliferated at a higher rate in microfluidic
      devices with continuous infusion of EGF. Furthermore, we found that ASC migrated
      toward an EGF gradient in microfluidic devices. Moreover, we found that ASC
      tended to position perpendicularly to dcEF. The results suggest that EGF and dcEF
      may be effective in guiding homing and trafficking of implanted ASC.

PMID- 23007450
TI  - Vocational rehabilitation evaluation and the International Classification of
      Functioning, Disability, and Health (ICF).
AB  - PURPOSE: To identify the most frequent functional limitations according to the
      International Classification of Functioning, Disability, and Health (ICF)
      obtained by unstandardised clinical assessment of patients with chronic
      musculoskeletal disorders who underwent vocational rehabilitation evaluation; and
      to compare the obtained list with simplified versions of ICF. METHODS: The
      descriptions of functional limitations were retrospectively identified for 32
      patients. The original vocational rehabilitation evaluation was conducted by a
      multi-professional team in an out-patient clinic of a university hospital. The
      obtained descriptions were converted to ICF codes, the most frequent being
      compared with the ICF Checklist of the World Health Organization (WHO) and the
      ICF Comprehensive and Brief Core Sets suggested by the ICF Research Branch.
      RESULTS: In the study population (53 % women), 141 ICF codes were identified with
      a preciseness of three or more digits, the average being 21 codes/subject (median
      20.0, range 9-40). When truncated to three digits, 84 ICF codes remained (average
      18 codes/subject, range 9-25), 45 of which appeared in over 10 % of the study
      population, 24 also being found in the ICF Comprehensive, 5 in the ICF Brief Core
      Sets, and 33 in the WHO ICF Checklist. CONCLUSIONS: The list of most frequent ICF
      codes retrospectively obtained in this study from unstandardised records showed a
      similarity with ICF Comprehensive and Brief Core Sets by ICF Research Branch and
      the ICF Checklist by WHO, but with a bias towards the identification of body
      structures and functions. The results support the use of ICF in vocational
      rehabilitation evaluation to ensure comprehensiveness of evaluation. The ICF
      Comprehensive Core Set seems to be the most useful for the needs of
      multiprofessional team when assessing functioning of patients.

PMID- 23007453
TI  - Behavioral medicine trial design: time for a change.

PMID- 23007455
TI  - Does motivational interviewing improve medication adherence?

PMID- 23007457
TI  - Raise the bar even higher for primary prevention interventions.

PMID- 23007459
TI  - The influence of old age and poloxamer-407 on the hepatic disposition of diazepam
      in the isolated perfused rat liver.
AB  - BACKGROUND AND PURPOSE: The normal liver sinusoidal endothelium is thin and
      punctuated with fenestrations 50-200 nm in diameter that filter endobiotics and
      xenobiotics. Defenestration of the liver sinusoidal endothelium in old age and
      after pre-treatment with poloxamer-407 (P407) has been shown to prevent the
      transfer of small chylomicrons across the liver sinusoidal endothelium. The aim
      of this study was to investigate the impact of liver sinusoidal endothelium
      fenestrations on the hepatic uptake of the highly protein-bound drug diazepam. We
      hypothesized that defenestration will reduce the hepatic extraction of drugs
      which are highly bound to albumin. METHODOLOGY: The isolated perfused rat liver
      (IPRL) model and multiple indicator dilution technique were used to investigate
      the effect of fenestrations in the liver sinusoidal endothelium on the hepatic
      disposition of diazepam in old and young rats, and in young rats treated with
      P407 or vehicle. A bolus dose of (14)C-diazpeam and non-extracted tracers ((3)H
      sucrose and Evans blue) was injected into the portal vein. The single-pass
      recovery of diazepam and markers and the apparent volume of distribution were
      determined. RESULTS: Scanning electron microscopy confirmed reduced porosity of
      the liver sinusoidal endothelial cells in P407-treated rats and old rats compared
      to young and control rats. The fractional recovery of diazepam was significantly
      increased in P407-treated rats compared to controls (0.20 +/- 0.16, n = 12, P407;
      0.08 +/- 0.05, n = 8, controls; p = 0.0029), and in old rats compared to young
      rats (0.15 +/- 0.03, n = 11, old; 0.10 +/- 0.02, n = 11, young; p = 0.0004)
      following a single pass. CONCLUSION: Defenestration due to age-related
      pseudocapillarization and treatment with P407 resulted in reduced hepatic
      extraction of diazepam after a single pass through the IPRL. These results
      highlight the importance of the liver sinusoidal endothelium in the
      ultrafiltration of highly protein-bound drugs, and may also provide an additional
      mechanism for reduced hepatic clearance of diazepam in conditions associated with
      defenestration.

PMID- 23007460
TI  - Recurrent cellulitis with benzathine penicillin prophylaxis is associated with
      diabetes and psoriasis.
AB  - Risk factors for recurrent cellulitis were assessed in a case-control study
      including 398 patients receiving prophylactic treatment with benzathine
      penicillin and 8,005 controls derived from a national population-based health
      survey. In the multivariate analysis, psoriasis [odds ratio (OR) 3.69], other
      chronic dermatoses (OR 4.14), diabetes (OR 1.65), increasing body mass index (OR
      1.17), increasing age (OR 1.06) and history of previous tonsillectomy (OR 6.82)
      were independently associated with recurrent cellulitis. Forty percent of the
      patients reported a cellulitis recurrence, despite ongoing benzathine penicillin
      prophylaxis. The role of previous tonsillectomy in recurrent cellulitis needs
      further evaluation.

PMID- 23007461
TI  - Molecular mechanisms of urea transport in health and disease.
AB  - In the late 1980s, urea permeability measurements produced values that could not
      be explained by paracellular transport or lipid phase diffusion. The existence of
      urea transport proteins were thus proposed and less than a decade later, the
      first urea transporter was cloned. The family of urea transporters has two major
      subgroups, designated SLC14A1 (or UT-B) and Slc14A2 (or UT-A). UT-B and UT-A gene
      products are glycoproteins located in various extra-renal tissues however, a
      majority of the resulting isoforms are found in the kidney. The UT-B (Slc14A1)
      urea transporter was originally isolated from erythrocytes and two isoforms have
      been reported. In kidney, UT-B is located primarily in the descending vasa recta.
      The UT-A (Slc14A2) urea transporter yields six distinct isoforms, of which three
      are found chiefly in the kidney medulla. UT-A1 and UT-A3 are found in the inner
      medullary collecting duct (IMCD), while UT-A2 is located in the thin descending
      limb. These transporters are crucial to the kidney's ability to concentrate
      urine. The regulation of urea transporter activity in the IMCD involves acute
      modification through phosphorylation and subsequent movement to the plasma
      membrane. UT-A1 and UT-A3 accumulate in the plasma membrane in response to
      stimulation by vasopressin or hypertonicity. Long-term regulation of the urea
      transporters in the IMCD involves altering protein abundance in response to
      changes in hydration status, low protein diets, or adrenal steroids. Urea
      transporters have been studied using animal models of disease including diabetes
      mellitus, lithium intoxication, hypertension, and nephrotoxic drug responses.
      Exciting new genetically engineered mouse models are being developed to study
      these transporters.

PMID- 23007462
TI  - Modulation of K2P3.1 (TASK-1), K2P9.1 (TASK-3), and TASK-1/3 heteromer by
      reactive oxygen species.
AB  - Reactive oxygen species (ROS) generated by mitochondria or NADPH oxidase have
      been implicated in the inhibition of K(+) current by hypoxia in chemoreceptor
      cells. As TASKs are highly active background K(+) channels in these cells, we
      studied the role of ROS in hypoxia-induced inhibition of TASKs. In HeLa cells
      expressing TASKs, H(2)O(2) applied to inside-out patches activated TASK-1, TASK
      3, and TASK-1/3 heteromer starting at ~16 mM. When applied to cell-attached or
      outside-out patches, 326 mM H(2)O(2) did not affect TASK activity. Other K(2P)
      channels (TREK-1, TREK-2, TASK-2, TALK-1, TRESK) were not affected by H(2)O(2)
      (tested up to 326 mM). A reducing agent (dithiothreitol) and a cysteine-modifying
      agent (2-aminoethyl methanethiosulfonate hydrobromide) had no effect on basal
      TASK activity and did not block the H(2)O(2)-induced increase in channel
      activity. A TASK mutant in which the C-terminus of TASK-3 was replaced with that
      of TREK-2 showed a normal sensitivity to H(2)O(2). Xanthine/xanthine oxidase
      mixture used to generate superoxide radical showed no effect on TASK-1, TASK-3,
      and TASK-1/3 heteromer from either side of the membrane, but it strongly
      activated TASK-2 from the extracellular side. Acute H(2)O(2) (32-326 mM) exposure
      did not affect hSlo1/b1(BK) expressed in HeLa cells and BK in carotid body glomus
      cells. In carotid body glomus cells, adrenal cortical cells, and cerebellar
      granule neurons that show abundant hypoxia-sensitive TASK activity, H(2)O(2) (>16
      mM) activated the channels only when applied intracellularly, similar to that
      observed with cloned TASKs. These findings show that ROS do not support or
      inhibit TASK and BK activity and therefore are unlikely to be the hypoxic signal
      that causes cell excitation via inhibition of these K(+) channels.

PMID- 23007463
TI  - On the different roles of AT1 and AT2 receptors in stretch-induced changes of
      connexin43 expression and localisation.
AB  - Cyclic mechanical stretch (CMS) and angiotensin II (ATII) play an important role
      in cardiac remodelling. Thus, we aimed to examine how ATII affects CMS-induced
      changes in localisation and expression of the gap junction protein connexin43
      (Cx43). Neonatal rat cardiomyocytes cultured on gelatin-coated Flexcell cell
      culture plates were kept static or were exposed to CMS (110 % of resting length,
      1 Hz) for 24 h with or without additional ATII (0.1 MUmol/L). Moreover,
      inhibitors of ATII receptors (AT-R) were used (for AT(1)-R: losartan 0.1 MUmol/L,
      for AT(2)-R: PD123177 0.1 MUmol/L). Thereafter, the cardiomyocytes were
      investigated by immunohistology, PCR and Western blot. After 24 h of CMS,
      cardiomyocytes were significantly elongated and orientated 75 +/- 1.6 degrees 
      nearly perpendicular to the stretch axis. Furthermore, CMS significantly
      accentuated Cx43 at the cell poles (ratio Cx43 polar/lateral static: 2.32 +/-
      0.17; CMS: 10.08 +/- 3.2). Additional ATII application significantly reduced Cx43
      polarisation (ratio Cx43 polar/lateral ATII: 4.61 +/- 0.42). The combined
      administration of ATII and losartan to CMS further reduced Cx43 polarisation to
      control levels, whilst the AT(2)-R blocker PD123177 restored polarisation.
      Moreover, CMS and ATII application resulted in a significant Cx43 protein and
      Cx43 mRNA up-regulation which could be blocked by losartan but not by PD123177.
      Thus, CMS results in a self-organisation of the cardiomyocytes leading to
      elongated cells orientated transversely towards the stretch axis with enhanced
      Cx43 expression and Cx43 accentuation at the cell poles. ATII enhances total Cx43
      mRNA and protein expression probably via AT(1)-R (=inhibitory effect of losartan)
      and reduces Cx43 polarisation presumably via AT(2)-R, since PD123177 (but not
      losartan) inhibited the negative effects of ATII on polarisation.

PMID- 23007464
TI  - Zinc modulation of basal and beta-adrenergically stimulated L-type Ca2+ current
      in rat ventricular cardiomyocytes: consequences in cardiac diseases.
AB  - Zinc exists in biological systems as bound and histochemically reactive free
      Zn(2+) in the nanomolar range. Zinc is required as either structural or catalytic
      component for a large number of enzymes. It also modulates current passage
      through many ion channels. Here, we reinvestigated the effects of extracellular
      and intracellular Zn(2+) on the L-type Ca(2+) current (I (CaL)) and its
      modulation by beta-adrenergic stimulation in rat ventricular cardiomyocytes. In
      the absence of Ca(2+) ions, Zn(2+) could permeate through the L-type channel at
      much lower concentrations and at a more positive voltage range, but with a lower
      permeability than Ca(2+). In the presence of Ca(2+), extracellular Zn(2+)
      demonstrated strong bimodal inhibitory effects on the I (CaL), with half
      inhibition occurring around 30 nM, i.e., in the range of concentrations found in
      the plasma. Intracellular Zn(2+) also significantly inhibited the I (CaL) with a
      half-inhibitory effect at 12.7 nM. Moreover, beta-adrenergic stimulation was
      markedly reduced by intracellular Zn(2+) at even lower concentrations (<1 nM) as
      a consequence of Zn(2+)-induced inhibition of the adenylyl cyclase. All these
      effects appeared independent of redox variations and were not affected by
      dithiothreitol. Thus, both basal intracellular and extracellular Zn(2+) modulate
      transmembrane Ca(2+) movements and their regulation by beta-adrenergic
      stimulation. Considering that, in many pathological situations, including
      diabetes, the extracellular Zn(2+) concentration is reduced and the intracellular
      one is increased, our results help to explain both Ca(2+) overload and marked
      reduction in the beta-adrenergic stimulation in these diseases.

PMID- 23007465
TI  - Improved localization of sestamibi imaging at high-volume centers.
AB  - OBJECTIVES/HYPOTHESIS: Sestamibi imaging can provide critical information
      regarding the location of suspected parathyroid adenomas. However, this modality
      can be challenging to perform and interpret reliably. The impact of experience on
      the localizing efficacy of sestamibi scanning was assessed. STUDY DESIGN:
      Prospective analysis of a consecutive series of patients undergoing
      parathyroidectomy was undertaken after institutional review board approval was
      obtained. METHODS: Patients undergoing parathyroid surgery from October 2003
      through June 2011 were considered. Inclusion criteria represented primary surgery
      for primary hyperparathyroidism, in which a single adenoma was excised and cure
      obtained. Sestamibi scan results, performed at our institution and at outside
      imaging centers, were compared to intraoperative findings. RESULTS: There were
      389 parathyroidectomies performed; 188 patients met inclusion criteria. Fifty
      four patients had sestamibi scans performed at outside institutions; 36 (67%)
      were localizing and 18 (33%) were nonlocalizing. Among localizing studies, half
      identified the correct quadrant and half recognized the correct side. At our
      institution, 147 patients underwent sestamibi imaging; 121 (82%) localized and 26
      (18%) did not. Among localizing studies, the correct quadrant was reported in 64%
      and the correct side in 36%. Of the 147 scans performed at our institution, 13
      represented repeat scans of patients with nonlocalizing outside scans. All 13 of
      these localized; six identified the correct quadrant and seven the side of the
      adenoma. CONCLUSIONS: A high volume of experience may improve the yield of
      sestamibi imaging. Repeating this study at a high-volume center when it was
      nonlocalizing elsewhere may provide useful additional information.

PMID- 23007466
TI  - Gene expression profiling for mechanistic understanding of cellular aggregation
      in mammalian cell perfusion cultures.
AB  - Aggregation of baby hamster kidney (BHK) cells cultivated in perfusion mode for
      manufacturing recombinant proteins was characterized. The potential impact of
      cultivation time on cell aggregation for an aggregating culture (cell line A) was
      studied by comparing expression profiles of 84 genes in the extracellular
      adhesion molecules (ECM) pathway by qRT-PCR from 9 and 25 day shake flask samples
      and 80 and 94 day bioreactor samples. Significant up-regulation of THBS2 (4.4- to
      6.9-fold) was seen in both the 25 day shake flask and 80 and 94 day bioreactor
      samples compared to the 9 day shake flask while NCAM1 was down-regulated 5.1- to
      8.9-fold in the 80 and 94 day bioreactor samples. Subsequent comparisons were
      made between cell line A and a non-aggregating culture (cell line B). A 65 day
      perfusion bioreactor sample from cell line B served as the control for 80 and 94
      day samples from four different perfusion bioreactors for cell line A. Of the 84
      genes in the ECM pathway, four (COL1A1, COL4A1, THBS2, and VCAN) were
      consistently up-regulated in cell line A while two (NCAM1 and THBS1) were
      consistently down-regulated. The magnitudes of differential gene expression were
      much higher when cell lines were compared (4.1- to 44.6-fold) than when early and
      late cell line B samples were compared (4.4- to 6.9-fold) indicating greater
      variability between aggregating and non-aggregating cell lines. Based on the
      differential gene expression results, two mechanistic models were proposed for
      aggregation of BHK cells in perfusion cultures.

PMID- 23007467
TI  - Possible role of transforming growth factor-beta1 and vascular endothelial growth
      factor in Fabry disease nephropathy.
AB  - Fabry disease is a lysosomal storage disorder (LSD) caused by deficiency of alpha
      galactosidase A (alpha-gal A), resulting in deposition of globotriaosylceramide
      (Gb3; also known as ceramide trihexoside) in the vascular endothelium of many
      organs. A gradual accumulation of Gb3 leads to cardiovascular, cerebrovascular
      and renal dysfunction. Endothelial cell dysfunction leads to renal complications,
      one of the main symptoms of Fabry disease. However, the pathological mechanisms
      by which endothelial dysfunction occurs in Fabry disease are poorly
      characterized. The purpose of this study was to investigate whether the
      expression of transforming growth factor-beta1 (TGF-beta1) and vascular
      endothelial growth factor (VEGF) is associated with the renal pathogenesis of
      Fabry disease. We found that the protein expression levels of renal
      thrombospondin-1 (TSP-1), TGF-beta1 and VEGF were higher in the kidneys from
      Fabry mice compared to wild-type mice. The expression levels of VEGF receptor 2
      (VEGFR2), fibroblast growth factor-2 (FGF-2) and phospho-p38 (P-p38) were also
      higher in the kidneys from Fabry mice compared with wild-type mice. Activities of
      cysteine aspartic acid protease (caspase)-6 and caspase-9 were higher in kidneys
      from Fabry than from the wild-type mice. These results suggest that
      overexpression of TGF-beta1 and VEGF in the Fabry mouse kidney might contribute
      to Fabry disease nephropathy by inducing apoptosis. To test whether Gb3
      accumulation can induce apoptosis, we incubated bovine aortic endothelial cells
      with Gb3 and found increased expression of TGF-beta1, VEGFR2, VEGF, FGF-2 and P
      p38. The combination of increased expression of TGF-beta1 and VEGF caused by Gb3
      accumulation may allow upregulation of FGF-2, VEGFR2 and P-p38 expression, and
      these changes may be associated with Fabry disease nephropathy by inducing
      apoptosis.

PMID- 23007468
TI  - Isolation of basal cells and submucosal gland duct cells from mouse trachea.
AB  - The large airways are directly in contact with the environment and therefore
      susceptible to injury from toxins and infectious agents that we breath in. The
      large airways therefore require an efficient repair mechanism to protect our
      bodies. This repair process occurs from stem cells in the airways and isolating
      these stem cells from the airways is important for understanding the mechanisms
      of repair and regeneration. It is also important for understanding abnormal
      repair that can lead to airway diseases. The goal of this method is to isolate a
      novel stem cell population from the mouse tracheal submucosal gland ducts and to
      place these cells in in vitro and in vivo model systems to identify the
      mechanisms of repair and regeneration of the submucosal glands. This production
      shows methods that can be used to isolate and assay the duct and basal stem cells
      from the large airways.This will allow us to study diseases of the airway, such
      as cystic fibrosis, asthma and chronic obstructive pulmonary disease. Currently,
      there are no methods for isolation of submucosal gland duct cells and there are
      no in vivo models to study the regeneration of submucosal glands.

PMID- 23007470
TI  - Tissue factor regulates tumor angiogenesis of retinoblastoma via the
      extracellular signal-regulated kinase pathway.
AB  - Retinoblastoma, a well-vascularized tumor that is dependent on a very robust
      angiogenic response, is the most common intraocular malignancy in children.
      Tissue factor (TF) is known to regulate tumor progression and in the present
      study we demonstrated that TF regulates tumor angiogenesis of retinoblastoma. In
      an orthotopic transplantation model of retinoblastoma, TF was selectively
      expressed in the proliferative area of retinoblastoma including tumor vessels as
      well as tumor cells, where TF expression was co-localized with endothelial cells
      of tumor vessels. TF expression progressively increased with fibroblast growth
      factor-2 (FGF-2)-induced proliferation of human umbilical vein endothelial cells
      (HUVECs), which was effectively inhibited by blockade of the TF pathway by TF
      pathway inhibitor (TFPI). In addition, FGF-2-induced angiogenic processes of
      migration and tube formation of vascular endothelial cells were also effectively
      suppressed by TFPI, which would be mediated by inhibition of extracellular signal
      regulated kinase activation. Therefore, further to our previous report that TF is
      involved in tumor cell proliferation of retinoblastoma, our current data suggest
      that blockade of the TF pathway by TFPI could effectively inhibit tumor growth by
      suppressing tumor cell proliferation and tumor angiogenesis at the same time.

PMID- 23007469
TI  - Protumor and antitumor functions of neutrophil granulocytes.
AB  - Neutrophils are primary inflammatory cells and absolutely essential to protect
      the host during the early phases of microbial infection. Their role in cancer is
      less clear. Current evidence suggests that neutrophils show high functional
      plasticity and can adopt protumor and antitumor activity. Protumor neutrophils
      are functionally related to the recently described granulocytic myeloid-derived
      suppressor cells. We propose a model in which homeostatic chronic recruitment and
      activation of neutrophils result in mainly protumor activity. In contrast,
      therapeutic interventions in many cases elicit acute activation, enhance direct
      effector functions as well as indirect regulatory functions of neutrophils with
      potent antitumor activity. Conversion of protumor activity of neutrophils into
      antitumor activity by means of appropriate stimulation or modulation may offer
      new possibilities in biologic therapy of cancer.

PMID- 23007476
TI  - IBD: Is measuring bone age in children with Crohn's disease useful?

PMID- 23007478
TI  - Transplantation: Graft surveillance in small bowel transplantation.

PMID- 23007479
TI  - Biliary tract: Is there a role for neoadjuvant and adjuvant therapy in biliary
      cancer?

PMID- 23007477
TI  - Therapeutic concepts in adult and paediatric eosinophilic oesophagitis.
AB  - Eosinophilic oesophagitis (EoE) was first described in the early 1990s. Although
      initially reported to be a rare entity, EoE has rapidly become a regularly
      diagnosed disease with a prevalence of approximately 1 in 2,000 individuals in
      the USA and Europe. The disease is characterized by a combination of oesophageal
      dysfunction and predominant eosinophilic infiltration of the oesophageal tissue.
      At diagnosis, other diseases that can be associated with oesophageal eosinophilic
      infiltration must be ruled out. Children with EoE present with a wide variety of
      symptoms, whereas adults mostly present with dysphagia for solid food and chest
      pain. Histologic features of EoE resemble those of T-helper type 2 inflammation.
      Endoscopy should be carried out to establish the diagnosis, but endoscopic
      abnormalities are not pathognomonic for EoE and the examination might not show
      histologic abnormality. Treatment modalities for EoE include drugs
      (corticosteroids, PPIs, antiallergic and biologic agents), hypoallergenic diets
      and oesophageal dilatation for strictures that are unresponsive to medical
      therapy. Unresolved eosinophilic inflammation leads to the formation of
      oesophageal strictures, which probably increase the risk of food bolus
      impactions. To date, long-term strategies for the therapeutic management of this
      chronic inflammatory disease remain poorly defined.

PMID- 23007480
TI  - Adenosine testing after cryoballoon pulmonary vein isolation improves long-term
      clinical outcome.
AB  - BACKGROUND: Adenosine infusion after pulmonary vein isolation (PVI) with
      radiofrequency energy reveals dormant muscular sleeves and predicts atrial
      fibrillation (AF) recurrence. The aim of our study was to determine whether
      adenosine could reveal dormant PV sleeves after cryoballoon isolation and study
      its effect on long-term recurrence of AF. METHODS: Patients with paroxysmal AF
      underwent cryoballoon PVI. After PVI, adenosine 25 mg was infused to test for
      dormant muscular sleeves in each vein. If reconnection under adenosine was shown,
      further cryoballoon ablation was performed until no more reconnection occurred.
      Follow-up was performed with ECG, 24-h Holter recording, and a symptom
      questionnaire at three monthly intervals. Transtelephonic Holter monitoring was
      performed for 1 month before and 3 months after PVI. Patients who underwent
      cryoballoon PVI without adenosine administration were used as controls for
      comparison. RESULTS: In the study group (n = 34, 24 males), adenosine revealed
      dormant sleeves in 9/132 (8 %) veins, and 7/34 (21 %) patients. All but one vein
      was further treated until the dormant sleeves were isolated. During a mean follow
      up of 520 +/- 147 days, 23/34 (68 %) patients were free of AF without
      antiarrhythmic drugs (AADs). In the control group (n = 65, 46 males), 29/65 (46
      %) were free of AF without AADs. There were significantly less AF recurrences in
      the study group (p = 0.04). CONCLUSIONS: Adenosine administration after
      cryoballoon PVI reveals dormant muscular sleeves in 21 % of patients. Clinical
      follow-up shows that adenosine testing is effective in reducing AF recurrence
      after cryoballoon ablation.

PMID- 23007481
TI  - Synthesis and enhanced DNA cleavage activities of bis-tacnorthoamide derivatives.
AB  - A new metal-free DNA cleaving reagent, bis-tacnorthoamide derivative 1 with two
      tacnorthoamide (tacnoa) units linked by a spacer containing anthraquinone, has
      been synthesized from triazatricyclo[5.2.1.0(4,10)]decane and characterized by
      NMR and mass spectrometry. For comparison, the corresponding compounds mono
      tacnorthoamide derivative 2 with one tacnorthoamide unit and 6 with two
      tacnorthoamide units linked by an alkyl (1,6-hexamethylene) spacer without
      anthraquinone have also been synthesized. The DNA-binding property investigated
      via fluorescence and CD spectroscopy suggests that compounds 1 and 2 have an
      intercalating DNA binding mode, and the apparent binding constants of 1, 2 and 6
      are 1.3 * 10(7) M(-1), 0.8 * 10(7) M(-1) and 8 * 10(5) M(-1), respectively.
      Agarose gel electrophoresis was used to assess plasmid pUC19 DNA cleavage
      activity promoted by 1, 2, 6 and parent tacnoa under physiological conditions,
      which gives rate constants k(obs) of 0.2126 +/- 0.0055 h(-1), 0.0620 +/- 0.0024
      h(-1), 0.040 +/- 0.0007 h(-1) and 0.0043 +/- 0.0002 h(-1), respectively. The 50
      fold and 15-fold rate acceleration over parent tacnoa is because of the
      anthraquinone moiety of compound 1 or 2 intercalating into DNA base pairs via a
      stacking interaction. Moreover, DNA cleavage reactions promoted by compound 1
      give 5.3-fold rate acceleration over compound 6, which further demonstrates that
      the introduction of anthraquinone results in a large enhancement of DNA cleavage
      activity. In particular, DNA cleavage activity promoted by 1 bearing two tacnoa
      units is 3.3 times more effective than 2 bearing one tacnoa unit and the DNA
      cleavage by compound 1 was achieved effectively at a relatively low concentration
      (0.03 mM). This dramatic rate acceleration suggests the cooperative catalysis of
      the two positively charged tacnoa units in compound 1. The radical scavenger
      inhibition study and ESI-MS analysis of bis(2,4-dinitrophenyl) phosphate (BDNPP)
      and adenylyl(3'-5')phosphoadenine (APA) cleavage in the presence of compound 1
      suggest the cleavage mechanism would be via a hydrolysis pathway by cleaving the
      phosphodiester bond of DNA.

PMID- 23007482
TI  - IBC's 23rd Antibody Engineering and 10th Antibody Therapeutics Conferences and
      the Annual Meeting of The Antibody Society: December 2-6, 2012, San Diego, CA.
AB  - Now in its 23rd and 10th years, respectively, the Antibody Engineering and
      Antibody Therapeutics conferences are the Annual Meeting of The Antibody Society.
      The scientific program covers the full spectrum of challenges in antibody
      research and development from basic science through clinical development. In this
      preview of the conferences, the chairs provide their thoughts on sessions that
      will allow participants to track emerging trends in (1) the development of next
      generation immunomodulatory antibodies; (2) the complexity of the environment in
      which antibodies must function; (3) antibody-targeted central nervous system
      (CNS) therapies that cross the blood brain barrier; (4) the extension of antibody
      half-life for improved efficacy and pharmacokinetics (PK)/pharmacodynamics (PD);
      and (5) the application of next generation DNA sequencing to accelerate antibody
      research. A pre-conference workshop on Sunday, December 2, 2012 will update
      participants on recent intellectual property (IP) law changes that affect
      antibody research, including biosimilar legislation, the America Invents Act and
      recent court cases. Keynote presentations will be given by Andreas Pluckthun
      (University of Zurich), who will speak on engineering receptor ligands with
      powerful cellular responses; Gregory Friberg (Amgen Inc.), who will provide
      clinical updates of bispecific antibodies; James D. Marks (University of
      California, San Francisco), who will discuss a systems approach to generating
      tumor targeting antibodies; Dario Neri (Swiss Federal Institute of Technology
      Zurich), who will speak about delivering immune modulators at the sites of
      disease; William M. Pardridge (University of California, Los Angeles), who will
      discuss delivery across the blood-brain barrier; and Peter Senter (Seattle
      Genetics, Inc.), who will present his vision for the future of antibody-drug
      conjugates. For more information on these meetings or to register to attend,
      please visit www.IBCLifeSciences.com/AntibodyEng or call 800-390-4078. Members of
      The Antibody Society and mAbs journal subscribers receive a 20% discount for
      meeting registration. To obtain this discount, email kdostie@ibcusa.com. mAbs is
      the official therapeutics journal of The Antibody Society and offers a discounted
      subscription to Society members for $49.

PMID- 23007483
TI  - Consumption of fruits and vegetables in Malaysia: profiling the daily and
      nondaily consumers.
AB  - This study examines the sociodemographic factors associated with daily fruit and
      vegetable (FV) consumption in Malaysia. Based on a cross-sectional sample of 2447
      individuals from the Malaysia Non-Communicable Disease Surveillance-1, a
      multivariate sample selection system is developed and estimated, to accommodate
      high frequencies of daily FV consumption and the days of servings among nondaily
      consumers. Results indicate that the authors' attempt to account for endogenous
      sample selectivity and cross-equation correlations is justified. There exist
      positive correlations between FV consumption likelihoods and longer work hours,
      higher levels of education, high income, female gender, nonsmoking status, and
      being from East Malaysia. Among nondaily consumers, those with longer work hours,
      singles, and people with diabetes are less inclined to eat fruits on more days.
      Overall, higher-educated, affluent people, nonsmokers, and East Malaysians
      display more days of FV consumption. Based on these outcomes, several policy
      implications are recommended vis-a-vis FV consumption patterns in Malaysia. 

PMID- 23007484
TI  - Differences between weekday and weekend levels of moderate-to-vigorous physical
      activity in Thai adolescents.
AB  - Attempts to reduce the decline in physical activity (PA) in adolescence have been
      the focus of many public health interventions. This study aimed to (1) determine
      differences in moderate-to-vigorous PA (MVPA) levels between weekdays and
      weekends and (2) identify adolescents meeting current PA guidelines (PAG). To
      meet these objectives, 186 Thai adolescents aged 13 to 18 years were asked to
      wear an ActiGraph accelerometer for 7 consecutive days. The results showed that
      MVPA levels were significantly higher in boys than girls on both weekdays (P <
      .01) and weekends (P < .05). MVPA was higher during weekdays compared with
      weekend days. Additionally, MVPA levels tend to decline with increasing age
      during adolescence. The results also showed statistically significant differences
      between genders in the proportion of adherence to PAG for youth. This study
      highlights the need to take weekend-weekday differences into account when
      developing PA interventions for adolescents. 

PMID- 23007485
TI  - The effects of potentiating stimuli intensity under varying rest periods on
      vertical jump performance and power.
AB  - Previous research has demonstrated that post-activation potentiation (PAP)
      increases in an intensity-dependent manner. However, these studies did not
      control for volume loads. The purpose of this study was to investigate the
      effects of varying intensities and rest period lengths, while controlling for
      volume load, on vertical jump (VJ) performance. Thirteen men, aged 21 +/- 3 years
      with an average relative full squat of 1.7 +/- 2 times their body weight, were
      recruited for this study. Participants were assigned to 3 different experimental
      sessions that required them to perform the back squat at 56% (low intensity), 70%
      (moderate intensity), and 93% (high intensity) of their 1 repetition maximums.
      Vertical jump height and power were recorded at 0, 2, 4, 8, and 12 minutes after
      squat. There was a significant condition by time interaction for VJ height and
      power, in which both variables did not change in the low-intensity condition,
      whereas decreasing immediately after squat for both the moderate- and high
      intensity conditions. In the moderate- and high-intensity conditions, VJ height
      and power increased and peaked at minute 4 and returned to baseline by minutes 8
      and 12. These results indicate that when controlling for total work, jump
      performance and power are enhanced similarly by moderate and high squat
      intensities. However, high-intensity workloads may prolong the duration of PAP.
      Therefore, athletes may use moderate- and high-intensity loads during warm-ups to
      improve jump performance and power.

PMID- 23007486
TI  - The effects of postactivation potentiation on golf club head speed.
AB  - In golf, an increase in club head speed (CHS) has been shown to increase driving
      distance and is correlated with handicap. The purpose of this study was to
      investigate the effect of a postactivation potentiation (PAP) intervention on
      CHS. A FlightScope launch monitor was used to record CHS in 16 golfers (aged 20.1
      +/- 3.24 years, handicap 5.8 +/- 2.26) during 2 testing sessions that were
      separated by 1 hour, using a counterbalanced design. The mean CHS of 3 swings was
      recorded with (experimental) and without (control) 3 preceding countermovement
      jumps (CMJs). An increase in CHS of 2.25 mph (effect size, 0.16; p < 0.05) 1
      minute after the CMJ intervention was recorded. Therefore, acute enhancements in
      CHS are possible when performing a CMJ before a golf drive. This may have
      implications for training and on-course performance enhancement as a result of
      increased driving distance and possible reductions in handicap; this PAP
      intervention is practically viable.

PMID- 23007487
TI  - Effect of compression garments on short-term recovery of repeated sprint and 3-km
      running performance in rugby union players.
AB  - The aim of this study was to investigate whether wearing compression garments
      during recovery improved subsequent repeated sprint and 3-km run performance. In
      a randomized single-blind crossover study, 22 well-trained male rugby union
      players (mean +/- SD: age 20.1 +/- 2.1 years, body mass 88.4 +/- 8.8 kg) were
      given a full-leg length compressive garment (76% Meryl Elastane, 24% Lycra) or a
      similar-looking noncompressive placebo garment (92% Polyamide, 8% Lycra) to wear
      continuously for 24 hours after performing a series of circuits developed to
      simulate a rugby game. After the 24-hour recovery, garments were removed and a 40
      m repeated sprint test (10 sprints at 30-second intervals), followed 10 minutes
      later by a 3-km run, was completed. One week later, the groups were reversed and
      testing repeated. Relative to the placebo, wearing the compressive garment
      decreased time to complete the 3 km by 2.0% +/- 1.9% (mean +/- 90% confidence
      interval). Additionally, average sprint times improved (1.2% +/- 1.5%) and
      fatigue was diminished (-15.8% +/- 26.1%) during the repeated sprint test in the
      compression group compared with the placebo group. Delayed onset muscle soreness
      was substantially lower in the compression group compared with the placebo group,
      48 hours after testing. Wearing compressive garments during recovery is likely to
      be worthwhile, and very unlikely to be harmful for well-trained rugby union
      players.

PMID- 23007488
TI  - Flexion-rotation trunk test to assess abdominal muscle endurance: reliability,
      learning effect, and sex differences.
AB  - Trunk endurance tests are generally performed in sagittal or frontal plane.
      However, trunk field tests that measure the endurance of the rotator muscles are
      lacking. In view of this situation, we developed a flexion-rotation trunk test
      (FRT test) to assess the oblique abdominal muscle endurance. This new field test
      consists mainly in performing the maximum number of upper trunk flexion and
      rotation movements (reps) possible in 90 seconds. The objectives of this study
      were to analyze the FRT test reliability and to examine the effect of both the
      repetition and sex on test results. Fifty-one recreationally trained men (n = 35)
      and women (n = 16) completed 4 trials of the FRT test (T1, T2, T3, and T4),
      separated by 7 days each. The scores increased significantly between T1 and T3 (p
      < 0.001), showing a clear learning effect, but the increase between T3 and T4 was
      only 4.25% (p = 0.108). The intraclass correlation coefficients (ICCs) between
      trials were >=0.83 and the standard errors of measurement (SEMs) <=7.54 reps. The
      ICCs between trials increased, and SEMs decreased with test repetition, reaching
      an ICC of 0.94 and an SEM of 6.46 reps between T3 and T4. The comparison between
      sexes showed a higher abdominal endurance in men when compared with that in women
      (p = 0.003), and also a higher learning effect in men, especially at the
      beginning of the study. These findings suggest that, the FRT test is a reliable
      field protocol that differentiates between the abdominal endurance of men and
      women. However, it is necessary to perform an extensive familiarization period
      before testing (at least 3 trials of practice) to make learning effect
      negligible.

PMID- 23007489
TI  - The effect of a short practical warm-up protocol on repeated sprint performance.
AB  - The aim of our study was to investigate the effect of a short, practical, 2-phase
      warm-up on repeated sprint performance when compared with more traditional warm
      up protocols that contain stretching activities. Eleven subelite male soccer
      players completed a warm-up protocol that commenced with 5 minutes jogging at
      approximately 65% of maximal heart rate, followed by no stretching, static
      stretching, or dynamic stretching and finishing with a task-specific high
      intensity activity. Using a crossover design, the 3 warm-up protocols were
      performed in a counterbalanced order with at least 48 hours between sessions.
      Repeated sprint performance was measured using a repeated sprint test that
      consisted of 6 * 40-m maximal sprints interspersed with a 20-second recovery.
      There were trivial differences in mean sprint time (0.2%) and posttest blood
      lactate (3.1%) between the 2-phase warm-up and the 3-phase warm-up that included
      dynamic stretching, whereas the short warm-up had a possibly detrimental effect
      on fastest sprint time (0.7%). Fastest (-1.1%) and mean (-1.2%) sprint times were
      quicker and posttest blood lactates were higher (13.2%) after the 2-phase warm-up
      when compared with the 3-phase warm-up that included static stretching. Although
      it is not harmful to complete a traditional 3-phase warm-up that includes dynamic
      stretching, it appears practical for athletes preparing for activities dependent
      on repeated sprint ability to complete a 2-phase warm-up consisting of a
      cardiovascular and specific high-intensity activity.

PMID- 23007490
TI  - Influence of the number of trials and the exercise to rest ratio in repeated
      sprint ability, with changes of direction and orientation.
AB  - The purpose of this investigation was to determine if there were different trends
      in physical fatigue observed in 3 different sets, of 7 trials each, in repeated
      sprint training, performed in 3 different modes: straight sprinting over 30 m,
      shuttle sprinting over 15 + 15 m, and sprinting over 30 m with changes of
      direction. Recovery time among trials in the sets was administered according to
      the 1:5 exercise to rest ratio. The sets were performed on 3 different days, with
      at least 48 hours between each set. The study involved 17 trained male soccer
      players (height, 177.33 +/- 6.21 cm; body mass, 71.63 +/- 9.58 kg; body mass
      index, 23 +/- 2.39 kg.m; age, 21.94 +/- 3.58 years). To compare the different
      values of the time recorded, an index of fatigue was used. Significant
      differences among trials within each set (repeated measures analysis of variance;
      p < 0.05) and between the sets (factorial analysis of variance; p < 0.001) were
      found. Significant correlations between each test and countermovement jump and
      stiffness values recorded pre exercise were found (p < 0.05). Significant
      differences between countermovement jump and stiffness values recorded pre and
      post exercise were also found (p < 0.05). This study suggests that training
      sessions aimed at increasing the capacity of repeated sprint ability in nonlinear
      and multidirectional sprints (shuttle and change of direction), which might imply
      a different number of trials within the set or different exercise to rest ratios
      from the ones usually adopted for straight sprinting, to induce similar trends of
      fatigue. As practical applications, the estimated numbers of necessary trials in
      the different sets and the possible exercise to rest ratios, resulting from
      mathematical modeling, are provided for each investigated sprinting mode.

PMID- 23007491
TI  - Relationship between the talk test and ventilatory thresholds in well-trained
      cyclists.
AB  - The aim of this study was to extend the range of populations where the Talk Test
      (TT) might be used as a marker of physiologic thresholds. Eighteen highly trained
      cyclists underwent 2 incremental tests. One test included measurement of
      respiratory gas exchange to determine the ventilatory (VT) and respiratory
      compensation thresholds (RCTs). On a separate day, a TT was performed using the
      same exercise protocol. During TT, subjects read a standard paragraph at the end
      of each stage. The first stage at which the cyclists could not talk comfortably
      and could definitely not talk were referred to as the equivocal (EQ) and the
      negative stages (NEG), respectively. There were no significant differences in
      workload, heart rate, lactate, and rating of perceived exertion between VT (3.7
      +/- 0.4 W kg, 150 +/- 10 b min, 1.6 +/- 0.3 mm L, and 4.1 +/- 1.4, respectively)
      vs. EQ (3.6 +/- 0.4 W kg, 148 +/- 12 b min, 1.3 +/- 0.5 mm L, and 3.8 +/- 1.2,
      respectively) and RCT (5.3 +/- 0.4 W kg, 177 +/- 7 b min, 4.0 +/- 0.9 mm L, and
      7.2 +/- 1.0, respectively) vs. NEG (5.3 +/- 0.5 W kg, 176 +/- 10 b min, 4.2 +/-
      1.3 mm L, and 6.8 +/- 1.5, respectively). We found significant relationships (p <
      0.01) between VT and EQ and RCT and NEG for workload (r = 0.86 and 0.94,
      respectively), heart rate (r = 0.79 and 0.92, respectively), and rating of
      perceived exertion (r = 0.79 and 0.88, respectively). In conclusion, the present
      study showed that the EQ and NEG stages of TT can be used as a simple and
      practical surrogate of the VT and RCT in highly trained cyclists.

PMID- 23007493
TI  - Superficial cooling does not decrease core body temperature before, during, or
      after exercise in an American football uniform.
AB  - The purpose of this study was to identify the effects of superficial cooling on
      thermoregulatory responses while exercising in a hot humid environment while
      wearing an American football uniform. Nine male and female subjects wore a
      superficial cooling garment while in a cooling (CS) experimental condition or a
      no cooling (NCS) control condition during an exercise task consisting of warm-up
      (WU), exercise (EX), and recovery (R). The exercise task simulated an American
      football conditioning session with subjects wearing a full American football
      uniform and performing anaerobic and aerobic exercises in a hot humid
      environment. Subjects were allowed to drink water ad libitum during rest breaks.
      During the WU, EX, and R periods, core body temperature (T(c)) was measured to
      assess the effect of the cooling garment. Neither baseline resting before warm-up
      T(c) nor after warm-up T(c) was significantly different between trials. No
      significant differences in exercise T(c) between conditions were found. Time to
      return to baseline T(c) revealed no significant differences between the
      experimental and control conditions. The authors found that the volume of fluid
      consumed was 34% less in the experimental condition (711.1 +/- 188.0 ml) compared
      with the control condition (1,077.8 +/- 204.8 ml). The findings indicate that the
      cooling garment was not effective in blunting the rise in T(c) during warm-up,
      attenuating a rise in T(c) during intermittent exercise, or in increasing a
      return to baseline T(c) during a resting recovery period in a hot humid
      environment while wearing an American football uniform.

PMID- 23007495
TI  - The MicroRNA.
AB  - MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both
      messenger RNA (mRNA) degradation and suppression of protein translation based on
      sequence complementarity between the miRNA and its targeted mRNA. Different names
      have been used to describe various types of miRNA. During evolution, RNA
      retroviruses or transgenes invaded the eukaryotic genome and inserted itself in
      the noncoding regions of DNA, conceivably acting as transposon-like jumping
      genes, providing defense from viral invasion and fine-tuning of gene expression
      as a secondary level of gene modulation in eukaryotes. When a transposon is
      inserted in the intron, it becomes an intronic miRNA, taking advantage of the
      protein synthesis machinery, i.e., mRNA transcription and splicing, as a means
      for processing and maturation. Recently, miRNAs have been found to play an
      important, but not life-threatening, role in embryonic development. They might
      play a pivotal role in diverse biological systems in various organisms,
      facilitating a quick response and accurate plotting of body physiology and
      structures. Based on these unique properties, manufactured intronic miRNAs have
      been developed for in vitro evaluation of gene function, in vivo gene therapy,
      and generation of transgenic animal models. The biogenesis and identification of
      miRNAs, potential applications, and future directions for research are presented
      in this chapter, hopefully providing a guideline for further miRNA and gene
      function studies.

PMID- 23007494
TI  - Sacrificial layer technique for axial force post assay of immature
      cardiomyocytes.
AB  - Immature primary and stem cell-derived cardiomyocytes provide useful models for
      fundamental studies of heart development and cardiac disease, and offer potential
      for patient specific drug testing and differentiation protocols aimed at cardiac
      grafts. To assess their potential for augmenting heart function, and to gain
      insight into cardiac growth and disease, tissue engineers must quantify the
      contractile forces of these single cells. Currently, axial contractile forces of
      isolated adult heart cells can only be measured by two-point methods such as
      carbon fiber techniques, which cannot be applied to neonatal and stem cell
      derived heart cells because they are more difficult to handle and lack a
      persistent shape. Here we present a novel axial technique for measuring the
      contractile forces of isolated immature cardiomyocytes. We overcome cell
      manipulation and patterning challenges by using a thermoresponsive sacrificial
      support layer in conjunction with arrays of widely separated elastomeric
      microposts. Our approach has the potential to be high-throughput, is functionally
      analogous to current gold-standard axial force assays for adult heart cells, and
      prescribes elongated cell shapes without protein patterning. Finally, we
      calibrate these force posts with piezoresistive cantilevers to dramatically
      reduce measurement error typical for soft polymer-based force assays. We report
      quantitative measurements of peak contractile forces up to 146 nN with post
      stiffness standard error (26 nN) far better than that based on geometry and
      stiffness estimates alone. The addition of sacrificial layers to future 2D and 3D
      cell culture platforms will enable improved cell placement and the complex
      suspension of cells across 3D constructs.

PMID- 23007496
TI  - Analysis of microRNA length variety generated by recombinant human Dicer.
AB  - miRNAs are a large subgroup of noncoding regulatory RNAs, which vary in length
      within the 20-25 nt range and show substantial length diversity and
      heterogeneity. To analyze the latter phenomenon, we recently developed high
      resolution northern blotting and employed this method to investigate cleavages
      generated by recombinant human Dicer in the synthetic miRNA precursors. We paid
      special care to visualize clearly the cleavages generated by the individual RNase
      III domains of Dicer. We have compared the results of northern blotting with the
      results of standard analysis with the use of end-labeled RNA and visualization of
      Dicer cleavage products by autoradiography. The point-by-point steps of substrate
      preparation, recombinant Dicer cleavage assay, and northern blotting are
      described in this manuscript.

PMID- 23007497
TI  - A user-friendly computational workflow for the analysis of microRNA deep
      sequencing data.
AB  - Second-generation high-throughput sequencing is a robust and inexpensive
      methodology that is becoming an increasingly common technique for the study of
      microRNA (miRNA) expression levels in the central nervous system. This method
      allows for the identification of both known and novel miRNAs, reporting on the
      qualitative and quantitative levels these RNA species represent in any given
      sample. Numerous bioinformatic programs are currently available to analyze deep
      sequencing data but many require at least a partial understanding of the command
      line interface. In this chapter, we describe a user-friendly computational
      workflow guiding the user through the process from the initial FASTQ deep
      sequencing file to the identification of known and potentially novel miRNAs in a
      given experiment, as well as the assessment of the differential expression of
      these miRNAs between experimental samples. Furthermore, programs that can predict
      potential targets for these miRNAs are also highlighted.

PMID- 23007498
TI  - The RNA gene information: retroelement-microRNA entangling as the RNA quantum
      code.
AB  - MicroRNA (miRNA) and retroelements may be a master of regulator in our life,
      which are evolutionally involved in the origin of species. To support the
      Darwinism from the aspect of molecular evolution process, it has tremendously
      been interested in the molecular information of naive RNA. The RNA wave model
      2000 consists of four concepts that have altered from original idea of the miRNA
      genes for crosstalk among embryonic stem cells, their niche cells, and
      retroelements as a carrier vesicle of the RNA genes. (1) the miRNA gene as a
      mobile genetic element induces transcriptional and posttranscriptional silencing
      via networking-processes (no hierarchical architecture); (2) the RNA information
      supplied by the miRNA genes expands to intracellular, intercellular, intraorgan,
      interorgan, intraspecies, and interspecies under the cycle of life into the
      global environment; (3) the mobile miRNAs can self-proliferate; and (4) cells
      contain two types information as resident and genomic miRNAs. Based on RNA wave,
      we have developed an interest in investigation of the transformation from RNA
      information to quantum bits as physicochemical characters of RNA with the
      measurement of RNA electron spin. When it would have been given that the
      fundamental bases for the acquired characters in genetics can be controlled by
      RNA gene information, it may be available to apply for challenging against RNA
      gene diseases, such as stress-induced diseases.

PMID- 23007499
TI  - Setting up an intronic miRNA database.
AB  - In the recent past, intragenic microRNAs (miRNAs) have gained significant
      attention. Due to the unique linkage to their host gene's transcription, these
      miRNAs offer more information than intergenic miRNAs as they associate with some
      of their hosts' properties. However, genome wide analysis of intronic miRNA data
      can be very challenging, especially if it relies on Web-based tools only. We
      therefore describe in this chapter how to set a database and how to link the
      different publicly available information resources on miRNAs and host genes. We
      also provide an example of a simple, but useful analysis technique. The basic
      structures and ideas suggested in this chapter can easily be extended to
      integrating other data and be applied to different analysis techniques.

PMID- 23007500
TI  - Identify intronic microRNA with bioinformatics.
AB  - MicroRNAs (miRNAs) are single-strand nonprotein coding RAN with 18 to 25
      nucleotides long. With complementary sequence to target messenger RNA (mRNA),
      miRNA regulates mRNA degradation and protein translation. miRNAs have been
      identified in various organisms ranging from virus to human. Increasing evidence
      indicates that mammalian gene regulation has multiple layers and the availability
      of mRNA is not the sole regulation mechanism. The evolutionally conserved miRNA
      may be a primary regulation mechanism of gene expression. Its role in directing
      embryo development and stem cell differentiation should not be underestimated.Due
      to the small size of miRNA, identifying it with experimental approach (e.g.,
      direct cloning) is difficult. The cell type and developmental-specific expression
      of miRNA make the experimental approach even more difficult. Consequently,
      bioinformatics approaches have been developed to identify novel miRNA. In human
      miRNA study, many studies search for the mostly complete human genomic sequence.
      Here, we report a rapid bioinformatics approach to mine miRNA from gene specific
      introns. Intronic miRNA may directly regulate the expression of its target genes
      during development. The reported bioinformatics approach not only identifies the
      potential miRNA, but also provides the intron location of these miRNA like
      sequence. This information is critical for studying the gene-gene interaction via
      miRNA, and facilitates the study of miRNA in gene expression regulation.

PMID- 23007501
TI  - Experimental miRNA target validation.
AB  - In the recent past, microRNAs (miRNAs) have gained significant attention as
      potent regulators of gene expression. These small noncoding RNA molecules are
      currently of major interest when investigating regulatory circuits of the cell.
      After identification of potential miRNA-target gene interactions (e.g., using
      computational algorithms), biomolecular validation is necessary. In the current
      chapter, we present a protocol for validation of an miRNA target interaction
      implying cloning of a dual-luciferase miRNA target expression vector,
      transfection of cells with this vector and a precursor miRNA (pre-miRNA), and the
      subsequent luciferase assay.

PMID- 23007502
TI  - Enrichment analysis of miRNA targets.
AB  - MicroRNAs (miRNAs) are a class of ~22-nucleotide endogenous noncoding RNAs which
      regulate target gene expression via repressing translation or promoting mRNAs
      degradation. Any individual mammalian miRNA often has more than a hundred
      predicted mRNA targets and that close to one thirds of all mRNA transcripts bear
      one or more conserved miRNA binding sites in their 3'-untranslated region.
      Enrichment analysis of miRNA targets has become a standard technique to
      elucidating hierarchical functions of miRNAs in gene regulatory networks. In this
      protocol, we discuss analytical methods and use of computational tools in a step
      by-step manner. Important details are also provided to help researchers choose
      more appropriate tools for a given type of analysis. Available Web-based
      resources for enrichment analysis of miRNA targets are summarized.

PMID- 23007503
TI  - MicroRNA expression profiling during neural differentiation of mouse embryonic
      carcinoma P19 cells.
AB  - The Mouse P19 cell line was derived from an embryonal carcinoma. The pluripotent
      P19 cells can be induced to differentiate into neuronal and glial cells. Here, we
      describe an miRNA microarray method to monitor the miRNA expression profiles
      during the course of P19 cells neuronal differentiation. The results indicated
      that there were significant differences between the miRNA expression in P19 EC
      cells and the resultant differentiated neural stem cells.

PMID- 23007504
TI  - Evaluating the microRNA targeting sites by luciferase reporter gene assay.
AB  - MicroRNAs are post-transcriptional regulators that control mRNA stability and the
      translation efficiency of their target genes. Mature microRNAs are approximately
      22-nucleotide in length. They mediate post-transcriptional gene regulation by
      binding to the imperfect complementary sequences (a.k.a. microRNA regulatory
      elements, MRE) in the target mRNAs. It is estimated that more than one-third of
      the protein-coding genes in the human genome are regulated by microRNAs. The
      experimental methods to examine the interaction between the microRNA and its
      targeting site(s) in the mRNA are important for understanding microRNA functions.
      The luciferase reporter gene assay has recently been adapted to test the effect
      of microRNAs. In this chapter, we use a previously identified miR-138 targeting
      site in the 3'-untranslated region (3'-UTR) of the RhoC mRNA as an example to
      describe a quick method for testing the interaction of microRNA and mRNA.

PMID- 23007505
TI  - Expression pattern analysis of microRNAs in Caenorhabditis elegans.
AB  - MicroRNAs (miRNAs) are ~22 nucleotide single-stranded RNA molecules that
      originate from hairpin precursors and regulate gene expression at the
      posttranscriptional level by basepairing with target messenger RNA and blocking
      its translation or inducing its degradation. miRNAs play important roles in a
      variety of biological processes, including development, proliferation,
      differentiation, cell fate determination, apoptosis, signal transduction, host
      viral interactions, and tumorigenesis. Methodological advances in miRNA studies
      allowed identification of biological roles for many miRNAs, and establishing the
      spatiotemporal expression patterns of miRNAs is one of the approaches to
      elucidate their biological functions. Expression pattern analysis of miRNAs helps
      to identify potential genetic interactors that exhibit similar expression
      patterns and this, combined with further supporting experiments, helps to
      identify the genetic pathways in which the specific miRNAs are involved. In this
      chapter, we describe a detailed protocol for the analysis of miRNA expression
      patterns in Caenorhabditis elegans.

PMID- 23007506
TI  - Use of viral systems to study miRNA-mediated regulation of gene expression in
      human cells.
AB  - MicroRNAs (miRNAs) are a class of small ~22 nt regulatory RNAs that modulate mRNA
      expression in all multicellular eukaryotic organisms. Interestingly, viruses also
      encode miRNAs and these viral miRNAs target cellular and viral mRNAs to regulate
      virus replication and latent infection. In particular, herpesviruses encode a
      large number of miRNAs. Herpesvirus infection also changes the normal expression
      profile of cellular miRNAs. New genetic tools have recently been generated to
      study the function of viral and cellular miRNAs in virus-infected cells. The
      creation of these reagents and use in Epstein-Barr virus-infected lymphoblastoid
      cell lines are discussed as a model viral system for the investigation of miRNA
      function.

PMID- 23007507
TI  - Cloning, expression, and functional analysis of genomic miRNA using retroviral
      system in cancer cells.
AB  - MicroRNAs have emerged as important post-transcriptional regulators of gene
      expression. Identification of cancer-regulated microRNAs or other classes of
      endogenous small RNAs have advanced our knowledge in cancer progression and
      metastasis. Among many tools, small RNA cloning is a powerful method to identify
      new microRNAs (miRNAs) and to profile miRNA expression and function. Retroviral
      system is also the minimum requirement for the studying of miRNAs in a highly
      stable population of cancer cells or other primary cell types with high
      expression. This chapter describes a step-by-step protocol that is optimized to
      clone directly one of the miRNA miR-145, as an example, from genomic DNA into
      retroviral vector to yield ultimate overexpression for functional study in
      prostate cancer cells. The small RNAs cloned by this protocol will have an easy
      and simple way of cloning from genomic DNA to maintain the necessary motifs of
      native enhancer for enhancement of mature miRNA expression. Furthermore, the
      procedure eliminates miRNA extraction and cDNA synthesis before cloning and
      sequential cloning of more than one miRNA makes this protocol cost- and time
      effective to eliminate many frequent cell culturing.

PMID- 23007508
TI  - Preparing synaptoneurosomes from adult mouse forebrain.
AB  - Many neuroscience studies involve subcellular fractionation to produce isolated
      or enriched synaptic fractions. Synaptosomes are prepared by flotation of
      synaptic membranes on sucrose or Percoll gradients. Alternatively,
      synaptoneurosomes are prepared by filtration of tissue homogenate through a
      series of filters to obtain a fraction that is enriched in pinched-off dendritic
      spines. Whereas the protocol for making synaptosomes is reasonably well
      standardized and well described in the literature, there is (to our knowledge) no
      detailed lab protocol for making synaptoneurosomes. Here, we give the methods
      used in our laboratory to produce synaptoneurosomes that are suitable for
      studying RNAs and proteins.

PMID- 23007509
TI  - Isolation of total RNA and detection procedures for miRNA present in bovine
      cultured adipocytes and adipose tissues.
AB  - Micro-ribonucleic acids (miRNA) regulate gene expression posttranscriptionally by
      altering translation of protein(s) encoded by specific messenger RNA. Therefore
      the ability to detect and quantify the expression levels of specific miRNA
      present within a cell or tissue is necessary to thoroughly examine cellular
      physiology and gene expression. Here we describe procedures that allow for the
      isolation and quantification of miRNA in bovine adipocytes and adipose tissue.

PMID- 23007510
TI  - miRNA and shRNA expression vectors based on mRNA and miRNA processing.
AB  - RNA interference (RNAi) has emerged as a powerful tool in basic research and
      therapeutics by silencing the expression of specific target genes. RNAi is
      triggered by double-stranded small interfering RNAs, which can be processed from
      naturally or artificially expressed microRNAs (miRNAs) or small hairpin RNAs
      (shRNAs). The development of reliable RNAi vectors encoding artificial and
      natural miRNAs would be useful tools for basic research and therapeutic
      applications. We reported a new type of new RNAi vectors, designated pSM155, and
      pSM30 that take into consideration of miRNA processing and RNA splicing by
      placing the miRNA-based artificial miRNA expression cassettes inside of synthetic
      introns. These vectors significantly improved the expression of an enhanced green
      fluorescent protein marker from the same mRNA transcript and also provide a
      simplified cloning method. We have described in this chapter the protocols for
      cloning artificial and natural miRNAs (or shRNAs), evaluating their efficiency in
      downregulating gene expression, and also discuss the potential applications of
      these vectors.

PMID- 23007511
TI  - Gene silencing in vitro and in vivo using intronic microRNAs.
AB  - MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering
      with intracellular messenger RNAs (mRNAs) that contain either complete or partial
      complementarity, are useful for the design of new therapies against cancer
      polymorphism and viral mutation. Numerous miRNAs have been reported to induce RNA
      interference (RNAi), a posttranscriptional gene-silencing mechanism. Recent
      evidence also indicates that they are involved in the transcriptional regulation
      of genome activities. They were first discovered in Caenorhabditis elegans as
      native RNA fragments that modulate a wide range of genetic regulatory pathways
      during embryonic development and are now recognized as small gene silencers
      transcribed from the noncoding regions of a genome. In humans, nearly 97% of the
      genome is noncoding DNA, which varies from one individual to another, and changes
      in these sequences are frequently noted to manifest in clinical and
      circumstantial malfunction; for example, type 2 myotonic dystrophy and fragile X
      syndrome were found to be associated with miRNAs derived from introns. Intronic
      miRNA is a new class of miRNAs derived from the processing of nonprotein-coding
      regions of gene transcripts. The intronic miRNAs differ uniquely from previously
      described intergenic miRNAs in the requirement of RNA polymerase (Pol)-II and
      spliceosomal components for its biogenesis. Several kinds of intronic miRNAs have
      been identified in C. elegans, mouse, and human cells; however, their functions
      and applications have not been reported. Here, we show for the first time that
      intron-derived miRNA is not only able to induce RNAi in mammalian cells, but also
      in fish, chicken embryos, and adult mice cells, demonstrating the evolutionary
      preservation of this gene regulation system in vivo. These miRNA-mediated animal
      models provide artificial means to reproduce the mechanisms of miRNA-induced
      disease in vivo and will shed further light on miRNA-related therapies.

PMID- 23007512
TI  - Vector-free methods for manipulating miRNA activity in vitro and in vivo.
AB  - Vector-based methods for manipulating microRNA (miRNA) activity in vivo and in
      vitro face a number of disadvantages regarding biosafety, workload, and potential
      for therapeutic use in patients. Use of miRNA mimics and inhibitors provides an
      alternative for enhancing or inhibiting translational repression of target genes
      that could be easier applied to elucidate miRNA function. Here, we describe in
      detail application of miRNA mimics and inhibitors in vitro using adherent cell
      lines. In addition, we describe a method how they could be applied in vivo in a
      possible therapeutic context and provide a protocol for validation of this
      intervention using miRNA target protectors. We present these methods within a
      standard experimental design workflow that could be followed and we discuss the
      technical challenges that have to be taken into account.

PMID- 23007513
TI  - MicroRNA expression profiling of human-induced pluripotent and embryonic stem
      cells.
AB  - Clinical implications of induced pluripotent stem (iPS) cell technology are
      enormous for personalized medicine. However, extensive use of viral approach for
      ectopic expression of reprogramming factors is a major hurdle in realization of
      its true potential. Non-viral methods for making iPS cells, although plausible,
      are impractical because of high cost. MicroRNAs are important cellular modulators
      that have been shown to rival transcription factors and are important players in
      embryonic development. We have generated distinct "microRNA-omes" signature of
      iPS cells that remain in a near embryonic stem (ES) cell state and distinct from
      differentiated cells. Recent advances in the microRNA field and experimentally
      validated microRNAs warrant a review in experimental protocols for microRNA
      expression profile.

PMID- 23007514
TI  - MicroRNA expression during neuronal differentiation of human teratocarcinoma
      NTera2D1 and mouse embryonic carcinoma P19 cells.
AB  - MicroRNAs (miRNAs) are 21-23-nucleotide-long small noncoding RNAs, function as
      mediators in gene silencing, and play essential roles in gene regulation in
      development, differentiation, and proliferation. Hundreds of miRNAs have been
      found, and tissue-specific or organ-specific expression of miRNAs has been
      detected. Here, I describe procedures for detection of miRNAs in the course of
      neuronal differentiation of human teratocarcinoma NTera2D1 and mouse embryonic
      carcinoma P19 cells.

PMID- 23007515
TI  - Isolation and identification of gene-specific microRNAs.
AB  - Computer programming has identified hundreds of genomic hairpin sequences, many
      with functions remain to be determined. Because direct transfection of hairpin
      like miRNA precursors (pre)-miRNAs in mammalian cells is not always sufficient to
      trigger effective RNA-induced gene silencing complex (RISC) assembly, a key step
      for RNA interference (RNAi)-related gene silencing, we developed an intronic
      miRNA-expressing system to overcome this problem by inserting a hairpin-like pre
      miRNA structure into the intron region of a gene and successfully increased the
      efficiency and effectiveness of miRNA-associated RNAi induction in vitro and in
      vivo. This intronic miRNA biogenesis has been found to depend on a coupled
      interaction of nascent precursor messenger RNA transcription and intron excision
      within a specific nuclear region proximal to genomic perichromatin fibrils. The
      intronic miRNA was transcribed by RNA type II polymerases, coexpressed with a
      primary gene transcript, and excised out of its encoding gene transcript by
      intracellular RNA splicing and processing mechanisms. Currently, some
      ribonuclease III endonucleases have been found to be involved in the processing
      of spliced introns and probably facilitating the intronic miRNA maturation. Using
      this miRNA generation system, we have shown for the first time that the intron
      derived miRNAs were able to induce strong RNAi effects in not only human and
      mouse cells but also zebrafishes, chicken embryos, and adult mice. We have also
      developed an miRNA isolation protocol, based on the complementarity between the
      designed miRNA and its target gene sequence, to purify and identify the mature
      miRNAs generated by the intronic miRNA-expressing system. Several intronic miRNA
      identities and structures are currently confirmed to be active in vitro and in
      vivo. According to this proven-of-principle method, we now have full knowledge to
      design pre-miRNA inserts that are more efficient and effective for the intronic
      miRNA-expressing systems.

PMID- 23007516
TI  - Transgene-like animal models using intronic microRNAs.
AB  - Transgenic animal models are valuable tools for testing gene functions and drug
      mechanisms in vivo. They are also the best similitude for a human body for
      etiological and pathological research of diseases. All pharmaceutically developed
      drugs must be proven to be safe and effective in animals before approval by the
      Food and Drug Administration to be used in clinical trials. To this end, the
      transgenic animal models of diseases serve as the front line of drug evaluation.
      However, there is currently no transgenic animal model for microRNA (miRNA)
      research. miRNAs, small single-stranded regulatory RNAs capable of silencing
      intracellular gene transcripts (mRNAs) that contain either complete or partial
      complementarity to the miRNA, are useful for the design of new therapies against
      cancer polymorphism and viral mutation. Recently, varieties of natural miRNAs
      have been found to derived from hairpin-like RNA precursors in almost all
      eukaryotes, including yeast (Schizosaccharomyces pombe), plant (Arabidopsis
      spp.), nematode (Caenorhabditis elegans), fly (Drosophila melanogaster), fish,
      mouse, and human, involving intracellular defense against viral infections and
      regulation of certain gene expressions during development. To facilitate the
      miRNA research in vivo, we have developed a state-of-the-art transgenic strategy
      for silencing specific genes in zebrafish, chicken, and mouse, using intronic
      miRNAs. By insertion of a hairpin-like pre-miRNA structure into the intron region
      of a gene, we have found that mature miRNAs were successfully transcribed by RNA
      polymerases type II (Pol II), coexpressed with the encoding gene transcript, and
      excised out of the encoding gene transcript by natural RNA splicing and
      processing mechanisms. In conjunction with retroviral transfection systems, the
      designed hairpin-like pre-miRNA construct was further tested to insert into the
      intron regions of a cellular gene for tissue-specific expression regulated by the
      gene promoter. Because the retroviral vectors were randomly integrated into the
      genome of its host cell, the most effective transgenic animal can be selected and
      propagated to be a stable transgenic line for future research. Here, we have
      shown for the first time that transgene-like animal models were generated using
      the intronic miRNA-expressing system described previously, which has been proven
      to be useful for both miRNA research and in vivo evaluation of miRNA-associated
      target gene functions.

PMID- 23007517
TI  - Mechanism and method for generating tumor-free iPS cells using intronic microRNA
      miR-302 induction.
AB  - Today's researchers generating induced pluripotent stem cells (iPS cells or
      iPSCs) usually consider the pluripotency first, then, the potential
      tumorigenicity. Oncogenic factors such as c-Myc and Klf4 were frequently used to
      boost the survival and proliferative rates of iPSCs, creating the inevitable
      problem of tumorigenicity that hindered the therapeutic usefulness of the iPSCs.
      To prevent tumorigenecity in stem cells, we have examined mechanism(s) by which
      the cell cycle genes of embryonic cells were regulated. Naturally occurring
      embryonic stem cells (ESCs) possess two unique stemness properties: pluripotent
      differentiation into almost all cell types and self-renewal with no risk of tumor
      formation. These two features are also important for the use of ESCs or iPSCs in
      therapy. Currently, despite overwhelming reports describing iPSC pluripotency,
      there have been no observations of tumor prevention mechanism(s) that suppresses
      tumor formation similar to that in naturally occurring ESCs. Our recent studies
      have revealed, for the first time, a ESC-specific microRNA (miRNA), miR-302,
      which was responsible for regulating human iPSC tumorigenicity through co
      suppression of both cyclin E-CDK2 and cyclin D-CDK4/6 cell cycle pathways during
      G1-S phase transition. Additionally, miR-302 also silenced BMI-1, a cancer stem
      cell marker gene, to promote the expression of two senescence-associated tumor
      suppressor genes, p16Ink4a and p14/p19Arf. Together, the combinatory effect of
      reducing G1-S cell cycle transition and increasing p16/p14(p19) expression
      resulted in a relatively attenuated cell cycle rate similar to that of 2-8-cell
      stage embryonic cells in early mammalian zygotes (20-24 h/cycle), as compared to
      the fast proliferation rate of iPSCs induced by four defined factors Oct4-Sox2
      Klf4-c-Myc (12-16 h/cycle). These findings provide a means to control iPSC
      tumorigenicity and improve the safety of iPSCs in the therapeutic use. In this
      chapter, we reviewed the mechanism underlying miR-302-mediated tumor suppression
      and then applied this mechanism to generate tumor-free iPSCs. The same strategy
      can also be used to prevent ESC tumorigenicity.

PMID- 23007518
TI  - Salivary microRNAs and oral cancer detection.
AB  - MicroRNAs (miRNAs) in human saliva have recently become an emerging field in
      saliva research for -diagnostics applications and its potential role in
      biological implications. miRNAs are short noncoding RNA molecules that play
      important roles in regulating a variety of cellular processes. Dysregulation of
      miRNAs are known to be associated with many diseases. miRNAs were found present
      in the saliva of OSCC patients and could serve as potential biomarkers for oral
      cancer detection. Understanding the biological function of miRNAs in association
      with diseases is important towards utilizing miRNAs as diagnostic markers. There
      are currently a variety of profiling methods available for detecting miRNA
      expression levels. In this chapter, we overview the Applied Biosystem Stem-loop
      RT based Taqman MicroRNA Assay for salivary miRNA profiling. Using this highly
      sensitive and specific assay, miRNAs in saliva are profiled with only a few
      nanograms of starting RNA. This method is also applicable for studying biomarkers
      in other body fluids or clinical samples that contain small amounts of RNA.

PMID- 23007519
TI  - Application of intronic microRNA agents in cosmetics.
AB  - MicroRNAs (miRNA) are short, single-stranded, noncoding RNAs that regulate a
      number of cellular processes through their capability to silence the expression
      of target proteins. Using miRNAs to target and reduce the expression of
      tyrosinase, the key enzyme involved in the synthesis of skin pigment melanin,
      presents a novel and feasible approach for achieving skin whitening. We have
      developed an artificial miRNA expression system that synthesizes miRNAs that
      downregulate tyrosinase expression by binding and degrading tyrosinase messenger
      RNAs. We used this anti-tyrosinase miRNA expression system (miR-Tyro) to
      successfully demonstrate the feasibility of miRNA-mediated skin whitening in
      vitro and in vivo. In light of bans of previously proven and popular skin
      whitening cosmetic ingredients such as hydroquinone and kojic acid, use of miRNAs
      that target and silence tyrosinase expression may present a novel and promising
      cosmetic approach to achieve skin whitening. Our finding on mirTyro-mediated skin
      whitening in mice is the first miRNA application proven to be feasible in vivo.

PMID- 23007521
TI  - MiRNA targets of prostate cancer.
AB  - Prostate cancer (PC) is the most prevalent strain of cancer in men, but it is
      often slow-acting or undetected. Common diagnostic tools for PC include prostate
      biopsy and consequent analysis by the Gleason scoring of the tissue samples, as
      well as tests for the presence and levels of prostate-specific antigens. Common
      treatments for androgen-dependent PC include prostatectomy or irradiation, which
      can be invasive and significantly lower the patient's quality of life.
      Alternative treatments exist, such as androgen ablation therapy, which, though
      effective, causes relapse into androgen-independent PC, which is far more
      invasive and likely to metastasize to other parts of the body. MicroRNAs (miRNA)
      are short nucleotide sequences (between 19 and 25 nucleotides long) that bind to
      various targeted messenger RNA (mRNA) sequences post-transcriptionally through
      complementary binding and control gene expression, often through silencing or
      leading to the degradation of targeted mRNA. Studies have shown that miRNAs are
      expressed abnormally in various cancers, suggesting that they play a pivotal role
      in cancer development and progression. Some miRNAs are oncogenes that incite
      cancerous growth, while others are involved in tumor suppression and cell cycle
      controls. MiRNA expression also differs in various types of cancers. Studies of
      PC-specific miRNAs show potential for their utilization in the prevention,
      diagnosis, and treatment of PC to more effectively target tumor growth and
      provide patients with better therapeutic options.

PMID- 23007520
TI  - MicroRNAs in skin and wound healing.
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules ~22 nucleotides in length
      that can post-transcriptionally repress gene expression. MiRNAs bind to their
      target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of
      translation. miRNAs have recently been shown to play pivotal roles in skin
      development and are linked to various skin pathologies, cancer, and wound
      healing. Chronic wounds represent a major health burden and drain on resources
      and developing more effective treatments is therefore a necessity. Increase in
      the understanding of the regulation of chronic wound biology is therefore
      required to develop newer therapies. This review focuses on the role of miRNAs in
      cutaneous biology, the various methods of miRNA modulation, and the therapeutic
      opportunities in treatment of skin diseases and wound healing.

PMID- 23007522
TI  - Overexpression of O-methyltransferase leads to improved vanillin production in
      baker's yeast only when complemented with model-guided network engineering.
AB  - Overproduction of a desired metabolite is often achieved via manipulation of the
      pathway directly leading to the product or through engineering of distant nodes
      within the metabolic network. Empirical examples illustrating the combined effect
      of these local and global strategies have been so far limited in eukaryotic
      systems. In this study, we compared the effects of overexpressing a key gene in
      de novo vanillin biosynthesis (coding for O-methyltransferase, hsOMT) in two
      yeast strains, with and without model-guided global network modifications.
      Overexpression of hsOMT resulted in increased vanillin production only in the
      strain with model-guided modifications, exemplifying advantage of using a global
      strategy prior to local pathway manipulation.

PMID- 23007524
TI  - Multilocus sequence analysis (MLSA) of 'Rickettsiella agriotidis', an
      intracellular bacterial pathogen of Agriotes wireworms.
AB  - Wireworms, the polyphagous larvae of click beetles belonging to the genus
      Agriotes (Coleoptera: Elateridae) are severe and widespread agricultural pests
      that affect numerous crops globally. A new bacterial specimen identified in
      diseased wireworms had previously been shown by microscopy and 16S ribosomal RNA
      (rRNA) gene-based phylogenetic reconstruction to belong to the taxonomic genus
      Rickettsiella (Gammaproteobacteria) that comprises intracellular bacteria
      associated with and typically pathogenic for a wide range of arthropods. Going
      beyond these earlier results obtained from rRNA phylogenies, multilocus sequence
      analysis (MLSA) using a four marker scheme has been employed in the molecular
      taxonomic characterization of the new Rickettsiella pathotype, referred to as
      'Rickettsiella agriotidis'. In combination with likelihood-based significance
      testing, the MLSA approach demonstrated the close phylogenetic relationship of
      'R. agriotidis' to the pathotypes 'Rickettsiella melolonthae' and 'Rickettsiella
      tipulae', i.e., subjective synonyms of the nomenclatural type species,
      Rickettsiella popilliae. 'R. agriotidis' forms, therefore, part of a
      Rickettsiella pathotype complex that most likely represents the species R.
      popilliae. As there are currently no genetic data available from the R. popilliae
      type strain, the respective assignment cannot be corroborated directly. However,
      an alternative taxonomic assignment to the species Rickettsiella grylli has been
      positively ruled out by significance testing. MLSA has been shown to provide a
      more powerful tool for taxonomic delineation within the genus Rickettsiella as
      compared to 16S rRNA phylogenetics. However, the limitations of the present MLSA
      scheme for the sub-species level classification of 'R. agriotidis' and further R.
      popilliae synonyms has been critically evaluated.

PMID- 23007523
TI  - Excess aldosterone-induced changes in insulin signaling molecules and glucose
      oxidation in gastrocnemius muscle of adult male rat.
AB  - Emerging evidences demonstrate that excess aldosterone and insulin interact at
      target tissues. It has been shown that increased levels of aldosterone contribute
      to the development of insulin resistance and thus act as a risk factor for the
      development of type-2 diabetes mellitus. However, the molecular mechanisms
      involved in this scenario are yet to be identified. This study was designed to
      assess the dose-dependent effects of aldosterone on insulin signal transduction
      and glucose oxidation in the skeletal muscle (gastrocnemius) of adult male rat.
      Healthy adult male albino rats of Wistar strain (Rattus norvegicus) weighing 180
      200 g were used in this study. Rats were divided into four groups. Group I:
      control (treated with 1 % ethanol only), group II: aldosterone treated (10 MUg
      /kg body weight, twice daily for 15 days), group III: aldosterone treated (20 MUg
      /kg body weight, twice daily for 15 days), and group IV: aldosterone treated (40
      MUg/kg body weight, twice daily for 15 days). Excess aldosterone caused glucose
      intolerance in a dose-dependent manner. Serum insulin and aldosterone were
      significantly increased, whereas serum testosterone was decreased. Aldosterone
      treatment impaired the rate of glucose uptake, oxidation, and insulin signal
      transduction in the gastrocnemius muscle through defective expression of IR, IRS
      1, Akt, AS160, and GLUT4 genes. Phosphorylation of IRS-1, beta-arrestin-2, and
      Akt was also reduced in a dose-dependent manner. Excess aldosterone results in
      glucose intolerance as a result of impaired insulin signal transduction leading
      to decreased glucose uptake and oxidation in skeletal muscle. In addition to
      this, it is inferred that excess aldosterone may act as one of the causative
      factors for the onset of insulin resistance and thus increased incidence of type
      2 diabetes.

PMID- 23007525
TI  - Distribution and diversity of acyl homoserine lactone producing bacteria from
      four different soils.
AB  - The distribution and diversity of acyl homoserine lactone (AHL) producing
      bacteria in black, brown, red, and meadow soils were investigated using culture
      dependent method. One out of seventy six and five out of fifty isolates from the
      black and the brown soil were AHL-biosensor active, respectively. They were
      affiliated to the genera Ensifer and Pseudomonas and the family
      Enterobacteriaceae. Thin layer chromatography showed that the most of them
      produced AHLs with acyl side chain of 6 or 8 carbons. No AHL-producer was found
      in red and meadow soils. A potential novel AHL-based quorum sensing and quenching
      system was identified by sequencing in the black soil isolate Ensifer adhaerens
      X097 that harbored two AHL synthetase-like proteins and one amidohydrolase-like
      protein. This is the first report of comparison of AHL-producers among different
      soils. Our data showed that composition of AHL-producers were niche specific and
      were not in proportion with community population.

PMID- 23007526
TI  - The effect of Aurora kinases on cell proliferation, cell cycle regulation and
      metastasis in renal cell carcinoma.
AB  - Aurora kinases have been shown to be involved in the regulation of the cell cycle
      and are related to tumor progression. This suggests the possibility that they can
      serve as new anticancer targets for tumor treatment. However, the important roles
      that Aurora kinases and their signaling pathway play in renal cell carcinoma
      (RCC) are not fully understood and addressed to date. In this study, we aimed to
      address these questions. We observed that downregulation of Aurora kinases
      induced by AurA miRNA, AurB miRNA or VX680 could inhibit proliferation and
      metastasis, induce G2/M phase arrest in clear cell renal cell carcinoma cells and
      exert antitumor activity in an SN12C xenograft model. We also show that either
      silencing of Aurora kinases or treating the cells with VX680 could downregulate
      the expression of cdc25c and cyclin B/cdc2, upregulate the expression of p-cdc2
      (Tyr15) via blocking the activity of ERK. All these changes may contribute to
      inhibition of proliferation, metastasis and G2/M arrest in ccRCC. In summary, we
      proved that both Aurora kinases A and B are key elements of tumor growth
      regulation, and inhibition of Aurora kinases may contribute to blocking ccRCC
      progression. We conclude that Aurora kinases could be potential therapeutic
      targets in the management of renal cell carcinoma.

PMID- 23007527
TI  - Ni2Sn2Zn from single-crystal X-ray diffraction.
AB  - Dinickel ditin zinc, Ni(2)Sn(2)Zn, crystallizes in the cubic space group Pm3m,
      with a lattice parameter of a = 8.845 (1) A and with all atoms occupying special
      positions. The crystal structure exhibits pronounced similarities with that of
      the quaternary compound Ni(5.20)Sn(8.7)Zn(4.16)Cu(1.04). It shares structural
      features with other compounds in the Ni-Sn-Zn system, such as Ni(5)Sn(4)Zn and
      Ni(3)Sn(2).

PMID- 23007528
TI  - [Te8][NbOCl4]2 containing an infinite chain-like {[Te-Te-Te-(Te5)]2+}n
      polycation.
AB  - The title compound, [Te(8)][NbOCl(4)](2), was obtained as translucent black
      crystals by reaction of elemental tellurium, niobium(V) chloride and niobium(V)
      oxychloride in the ionic liquid BMImCl (BMImCl is 1-butyl-3-methylimidazolium
      chloride). The synthesis was performed in argon-filled glass ampoules. According
      to X-ray structure analysis based on single crystals, the title compound
      crystallizes with triclinic lattice symmetry and consists of infinite
      {[Te(8)](2+)}(n) cations associated with pyramidal [NbOCl(4)](-) anions. The
      novel catena-octatellurium(2+) cation is composed of Te(5) rings that are linked
      via Te(3) units [Te-Te = 2.6455 (18)-2.8164 (19) A]. The composition and purity
      of [Te(8)][NbOCl(4)](2) were further confirmed by energy-dispersive X-ray
      diffraction (EDX) analysis.

PMID- 23007529
TI  - Monodentate and bridging behaviour of the sulfur-containing ligand 4'-[4
      (methylsulfanyl)phenyl]-4,2':6',4''-terpyridine in two discrete zinc(II)
      complexes with acetylacetonate.
AB  - The Zn complexes bis(acetylacetonato-kappa(2)O,O')bis{4'-[4
      (methylsulfanyl)phenyl]-4,2':6',4''-terpyridine-kappaN(1)}zinc(II),
      [Zn(C(5)H(7)O(2))(2)(C(22)H(17)N(3)S)(2)], (I), and {MU-4'-[4
      (methylsulfanyl)phenyl]-4,2':6',4''-terpyridine
      kappa(2)N(1):N(1'')}bis[bis(acetylacetonato-kappa(2)O,O')zinc(II)],
      [Zn(2)(C(5)H(7)O(2))(4)(C(22)H(17)N(3)S)], (II), are discrete entities with
      different nuclearities. Compound (I) consists of two centrosymmetrically related
      monodentate 4'-[4-(methylsulfanyl)phenyl]-4,2':6',4''-terpyridine (L1) ligands
      binding to one Zn(II) atom sitting on an inversion centre and two
      centrosymmetrically related chelating acetylacetonate (acac) groups which bind
      via carbonyl O-atom donors, giving an N(2)O(4) octahedral environment for Zn(II).
      Compound (II), however, consists of a bis-monodentate L1 ligand bridging two
      Zn(II) atoms from two different Zn(acac)(2) fragments. Intra- and intermolecular
      interactions are weak, mainly of the C-H...pi and pi-pi types, mediating similar
      layered structures. In contrast to related structures in the literature, sulfur
      mediated nonbonding interactions in (II) do not seem to have any significant
      influence on the supramolecular structure.

PMID- 23007530
TI  - Two tetranuclear zinc clusters, [Zn4(MU3-OEt)2(MU2-MalO)4Et2] and [Zn4(MU3
      GueO)2(MU2-GueO)2(MU2-MalO)2(MalO)2].2C7H8, containing defective dicubane core
      geometries (MalOH is maltol and GueOH is guethol).
AB  - The zinc alkoxide molecules in di-MU(3)-ethanolato-diethyltetrakis(MU(2)-2-methyl
      4-oxo-4H-pyran-3-olato-kappa(3)O(3),O(4):O(3))tetrazinc(II),
      [Zn(4)(C(2)H(5))(2)(C(2)H(5)O)(2)(C(6)H(5)O(3))(4)], (I), and bis(MU(3)-2
      ethoxyphenolato-kappa(4)O(1),O(2):O(1):O(1))bis(MU(2)-2-ethoxyphenolato
      kappa(3)O(1),O(2):O(1))bis(MU(2)-2-methyl-4-oxo-4H-pyran-3-olato
      kappa(3)O(3),O(4):O(3))bis(2-methyl-4-oxo-4H-pyran-3-olato
      kappa(2)O(3),O(4))tetrazinc(II) toluene disolvate,
      [Zn(4)(C(6)H(5)O(3))(4)(C(8)H(9)O(2))(4)].2C(7)H(8), (II), lie on
      crystallographic centres of inversion. The asymmetric units of (I) and (II)
      contain half of the tetrameric unit and additionally one molecule of toluene for
      (II). The Zn(II) atoms are four- and six-coordinated in distorted tetrahedral and
      octahedral geometries for (I), and six-coordinated in a distorted octahedral
      environment for (II). The Zn(II) atoms in both compounds are arranged in a defect
      dicubane Zn(4)O(6) core structure composed of two EtZnO(3) tetrahedra and ZnO(6)
      octahedra for (I), and of four ZnO(6) octahedra for (II), sharing common corners.
      The maltolate ligands exist mostly in a MU(2)-bridging mode, while the guetholate
      ligands prefer a higher coordination mode and act as MU(3)- and MU(2)-bridges.

PMID- 23007531
TI  - catena-poly[[silver(I)-MU-[9,10-bis(1H-benzimidazol-1-ylmethyl)anthracene]
      kappa2N3:N3'] bis(nitrato-kappaO)silver(I)].
AB  - Yellow needle-shaped crystals of the title compound,
      {[Ag(C(30)H(22)N(4))][Ag(NO(3))(2)]}(n), were obtained by the reaction of AgNO(3)
      and 9,10-bis(benzimidazol-1-ylmethyl)anthracene (L) in a 2:1 ratio. The
      asymmetric unit consists of two Ag(I) cations, one half L ligand and one nitrate
      anion. One Ag(I) cation occupies a crystallographic inversion centre and links
      two N-atom donors of two distinct L ligands to form an infinite one-dimensional
      coordination polymer. The second Ag(I) cation lies on a crystallographic twofold
      axis and is coordinated by two O-atom donors of two nitrate anions to form an
      [Ag(NO(3))(2)](-) counter-ion. The polymeric chains are linked into a
      supramolecular framework via weak Ag...O [3.124 (5) A] and Ag...pi (2.982 A)
      interactions (pi is the centroid of an outer anthracene benzene ring). The pi
      interactions contain two short Ag...C contacts [2.727 (6) and 2.765 (6) A], which
      can be considered to define Ag-eta(2)-anthracene bonding interactions. In
      comparison with a previously reported binuclear Ag(I) complex [Du, Hu, Zhang,
      Zeng & Bu (2008). CrystEngComm, 10, 1866-1874], this new one-dimensional
      coordination polymer was obtained by changing the metal-ligand ratio during the
      synthesis.

PMID- 23007532
TI  - Poly[[bis{MU2-N2,N6-bis[(pyridin-3-yl)methyl]pyridine-2,6
      dicarboxamide}dichloridonickel(II)] N,N-dimethylformamide tetrasolvate].
AB  - In the title compound, {[NiCl(2)(C(19)H(17)N(5)O(2))(2)].4C(3)H(7)NO}(n), the
      Ni(II) atom is located on an inversion centre and is in a six-coordinated
      octahedral geometry, formed by four pyridine N atoms from four N(2),N(6)
      bis[(pyridin-3-yl)methyl]pyridine-2,6-dicarboxamide (BPDA) ligands occupying the
      equatorial plane and two chloride anions at the axial sites. The bidentate
      bridging BPDA ligands link the Ni(II) atoms into a two-dimensional corrugated
      grid-like flexible layer with a (4,4)-connected topology, which consists of left-
      and right-handed helical chains sharing the common Ni(II) atoms. Investigation of
      the thermal stability shows that the network is stable up to 573 K.

PMID- 23007533
TI  - Magnetic properties of a mononuclear iron(II) complex with a typical FeN6
      coordination octahedron.
AB  - A mononuclear iron(II) complex with the tripodal ligand bis(pyridin-2
      ylmethyl)(quinolin-2-ylmethyl)amine (dpqa) has been synthesized and structurally
      characterized, namely [bis(pyridin-2-ylmethyl)(quinolin-2-ylmethyl)amine
      kappa(4)N,N',N'',N''']bis(thiocyanato-kappaS)iron(II),
      [Fe(NCS)(2)(C(22)H(20)N(4))], exhibits a three-dimensional supramolecular network
      via pi-pi interactions and S...H-C hydrogen-bonding interactions between adjacent
      Fe(II) centres. Temperature-dependent magnetic measurements under different
      external pressures and X-ray diffraction measurements indicate that all the
      Fe(II) centres in this complex retain a high-spin state upon cooling from 300 to
      2 K. The surprising absence of spin-crossover behaviour for this mononuclear
      iron(II) complex is attributed to the steric hindrance originating from the
      substituted quinoline ring in the dpqa ligand.

PMID- 23007534
TI  - The heterobifunctional ligand 5-[4-(1,2,4-triazol-4-yl)phenyl]-1H-tetrazole and
      its role in the construction of a CdII metal-organic chain structure.
AB  - 5-[4-(1,2,4-Triazol-4-yl)phenyl]-1H-tetrazole, C(9)H(7)N(7), (I), an asymmetric
      heterobifunctional organic ligand containing triazole (tr) and tetrazole (tz)
      termini linked directly through a 1,4-phenylene spacer, crystallizes in the polar
      space group Pc. The heterocyclic functions, serving as single hydrogen-bond donor
      (tz) or acceptor (tr) units, afford hydrogen-bonded zigzag chains with no
      crystallographic centre of inversion. In the structure of catena
      poly[[diaquacadmium(II)]bis{MU(2)-5-[4-(1,2,4-triazol-4-yl)phenyl]tetrazol-1-ido
      kappa(2)N(1):N(1')}], [Cd(C(9)H(6)N(7))(2)(H(2)O)(2)](n), (II), the Cd(II)
      dication resides on a centre of inversion in an octahedral {N(4)O(2)}
      environment. In the equatorial plane, the Cd(II) polyhedron is built up from four
      N atoms of two kinds, namely of trans-coordinating tr and tz fragments [Cd-N =
      2.2926 (17) and 2.3603 (18) A], and the coordinating aqua ligands occupy the two
      apical sites. The metal centres are separated at a distance of 11.1006 (7) A by
      means of the double-bridging tetrazolate anion, L(-), forming a chain structure.
      The water ligands and tz fragments interact with one another, like a double
      hydrogen-bond donor-acceptor synthon, leading to a hydrogen-bonded three
      dimensional array.

PMID- 23007535
TI  - Planarity of benzoylhydrazine-dithiocarbazoate tuberculostatics. I. N'-Methyl
      substituted 3,4-dichlorobenzoyl monoesters.
AB  - Methyl 2-(3,4-dichlorobenzoyl)-1-methylhydrazinecarbodithioate,
      C(10)H(10)Cl(2)N(2)OS(2), (F1), butyl 2-(3,4-dichlorobenzoyl)-1
      methylhydrazinecarbodithioate, C(13)H(16)Cl(2)N(2)OS(2), (F2), and 3,4-dichloro-N
      (2-sulfanylidene-1,3-thiazinan-3-yl)benzamide, C(11)H(10)Cl(2)N(2)OS(2), (F3),
      were studied by X-ray diffraction to test our hypothesis that planarity of
      aryloylhydrazinedithiocarbazic acid esters is a prerequisite for tuberculostatic
      activity. All compounds examined in this study are inactive and nonplanar due to
      twists along two specific bonds in the central frame of the molecules. The
      significant twist at the N-N bond, with an C-N-N-C(S) torsion angle of about 85
      degrees , results from repulsion caused by a methyl substituent at the N' atom of
      the hydrazide group. The other twist is that within the benzoyl group at the C(O)
      Ph bond, i.e. the N-C(=O)-C(phenyl)-C torsion angle: the values found in the
      studied structures (25-30 degrees ) are in agreement with those observed in other
      compounds containing a similar fragment. As some nonplanar benzoyl derivatives
      are active, it seems that planarity of the hydrazinedithioate fragment is more
      important for tuberculostatic activity than planarity of the aryloyl group.

PMID- 23007536
TI  - 4,6-Diaminopyrimidine-2(1H)-thione hemihydrate: a three-dimensional hydrogen
      bonded framework.
AB  - In the title compound, C(4)H(6)N(4)S.0.5H(2)O, there are two independent
      pyrimidinethione units, both of which lie across mirror planes in the space group
      Cmca. Hence, the H atoms bonded to the ring N atoms in each molecule are
      disordered over two symmetry-related sites, each having an occupancy of 0.5. The
      water molecule lies across a twofold rotation axis parallel to [010]. The
      molecular components of (I) are linked by seven independent hydrogen bonds, of N
      H...N, N-H...S, N-H...O and O-H...S types. A combination of disordered N-H...N
      hydrogen bonds and ordered N-H...S hydrogen bonds links the pyrimidinethione
      units into a continuous tubular structure. The water molecule acts as both a
      double donor of hydrogen bonds and a double acceptor, forming hydrogen bonds with
      components of four distinct pyrimidinethione tubes, thus linking these tubes into
      a three-dimensional structure.

PMID- 23007537
TI  - Bis(tert-butyldimethylsilyl)(2,6-diisopropylphenyl)phosphane: the first structure
      of an organophosphane with two tert-butyldimethylsilyl (TBDMS) substituents.
AB  - The title compound, C(24)H(47)PSi(2), is the first organophosphane bearing two
      tert-butyldimethylsilyl (TBDMS) groups to be crystallographically characterized,
      even though TBDMS is a very popular bulky silyl group. The structure is a
      considerably flattened trigonal pyramid, with the sum of the C/Si-P-C/Si angles
      being 333.35 (6) degrees , which can be attributed to the steric pressure from
      the three bulky groups. The P-Si distances [2.2605 (6) and 2.2631 (6) A] are
      normal, while the P-C distance [1.8646 (12) A] is long (outside the s.u. values)
      compared with related structures. The plane of the aryl ring approximately
      bisects the Si-P-Si angle, quite unlike the secondary (tert
      butyldimethylsilyl)(2,6-diisopropylphenyl)phosphane bearing only one TBDMS group,
      in which the single Si atom is perpendicular to the aryl ring. The title
      structure conforms closely to that predicted from B3LYP/6-31G(d) calculations,
      although the calculations overestimate the degree of planarity. The compound
      crystallizes centrosymmetrically in the space group P1 as isolated molecules.

PMID- 23007538
TI  - Helical self-assembly of 2-(1,4,7,10-tetraazacyclododecan-1-yl)cyclohexan-1-ol
      (cycyclen).
AB  - The title macrocyclic amino alcohol compound, C(14)H(30)N(4)O, is investigated as
      a solid-state synthon for the design of a self-assembled tubular structure. It
      crystallizes in a helical column constructed by stereospecific O-H...N and N
      H...N interactions. The hydrogen-bonding interactions, dependent upon macrocyclic
      ring helicity and molecular conformation, link R,R and S,S enantiomers in a head
      to-tail fashion, forming a continuous hydrophilic inner core.

PMID- 23007540
TI  - Isoquinolin-5-amine.
AB  - The title compound, C(9)H(8)N(2), presents two almost identical independent
      molecules in the asymmetric unit, both of them exhibiting an extremely planar
      isoquinoline core (maximum r.m.s. deviation = 0.014 A). The most significant
      deviation is found in the -NH(2) groups, which present a noticeable
      pyramidalization around the N atom, a feature also present in related structures
      containing the molecule as a ligand. The supramolecular structure is based on
      pairs of parallel hydrogen-bonded chains formed by just one molecular type each,
      defined by the strongest hydrogen bonds in the structure, which are of the N
      H...N type. These parallel chains are linked into pairs (or strips) via weaker C
      H...N hydrogen bonds. Related strips generated by the c-glide plane define two
      families running along [110] and [110], giving rise to an interesting system of
      interwoven chains stabilized by a number of weaker contacts of the C-H...pi type.

PMID- 23007539
TI  - Three anilides of 2,2'-thiodibenzoic acid.
AB  - The structures of N,N'-bis(2-methylphenyl)-2,2'-thiodibenzamide,
      C(28)H(24)N(2)O(2)S, (Ia), N,N'-bis(2-ethylphenyl)-2,2'-thiodibenzamide,
      C(30)H(28)N(2)O(2)S, (Ib), and N,N'-bis(2-bromophenyl)-2,2'-thiodibenzamide,
      C(26)H(18)Br(2)N(2)O(2)S, (Ic), are compared with each other. For the 19 atoms of
      the consistent thiodibenzamide core, the r.m.s. deviations of the molecules in
      pairs are 0.29, 0.90 and 0.80 A for (Ia)/(Ib), (Ia)/(Ic) and (Ib)/(Ic),
      respectively. The conformations of the central parts of molecules (Ia) and (Ib)
      are similar due to an intramolecular N-H...O hydrogen-bonding interaction. The
      molecules of (Ia) are further linked into infinite chains along the c axis by
      intermolecular N-H...O interactions, whereas the molecules of (Ib) are linked
      into chains along b by an intermolecular N-H...pi contact. The conformation of
      (Ic) is quite different from those of (Ia) and (Ib), since there is no
      intramolecular N-H...O hydrogen bond, but instead there is a possible
      intramolecular N-H...Br hydrogen bond. The molecules are linked into chains along
      c by intermolecular N-H...O hydrogen bonds.

PMID- 23007541
TI  - 5-Ethynyl-2'-deoxycytidine: a DNA building block with a 'clickable' side chain.
AB  - The title compound [systematic name: 4-amino-1-(2-deoxy-beta-D-erythro
      pentofuranosyl)-5-ethynylpyrimidin-2(1H)-one], C(11)H(13)N(3)O(4), shows two
      conformations in the crystalline state. The N-glycosylic bonds of both conformers
      adopt similar conformations, with chi = -149.2 (1) degrees  for conformer (I-1)
      and -151.4 (1) degrees  for conformer (I-2), both in the anti range. The sugar
      residue of (I-1) shows a C2'-endo envelope conformation ((2)E, S-type), with P =
      164.7 (1) degrees  and tau(m) = 36.9 (1) degrees , while (I-2) shows a major C3'
      exo sugar pucker (C3'-exo-C2'-endo, (3)T(2), S-type), with P = 189.2 (1) degrees 
      and tau(m) = 33.3 (1) degrees . Both conformers participate in the formation of a
      layered three-dimensional crystal structure with a chain-like arrangement of the
      conformers. The ethynyl groups do not participate in hydrogen bonding, but are
      arranged in proximal positions.

PMID- 23007542
TI  - Three new [XC(O)NH]P(O)[N(CH2C6H5)2]2 phosphoric triamides (X = CClF2, 3-F-C6H4
      and 3,5-F2-C6H3): a database analysis of tertiary N-atom geometry in compounds
      with a C(O)NHP(O)[N]2 core.
AB  - In the phosphoric triamides N,N,N',N'-tetrabenzyl-N''-(2-chloro-2,2
      difluoroacetyl)phosphoric triamide, C(30)H(29)ClF(2)N(3)O(2)P, (I), N,N,N',N'
      tetrabenzyl-N''-(3-fluorobenzoyl)phosphoric triamide, C(35)H(33)FN(3)O(2)P, (II),
      and N,N,N',N'-tetrabenzyl-N''-(3,5-difluorobenzoyl)phosphoric triamide,
      C(35)H(32)F(2)N(3)O(2)P, (III), the tertiary N atoms of the dibenzylamido groups
      have sp(2) character with minimal deviation from planarity. The sums of the three
      bond angles about the N atoms in (I)-(III) deviate by less than 8 degrees  from
      the planar value of 360 degrees . The geometries of the tertiary N atoms in all
      phosphoric triamides with C(O)NHP(O)[N](2) skeletons deposited in the Cambridge
      Structural Database [CSD; Allen (2002). Acta Cryst. B58, 380-388] have been
      examined and the bond-angle sums at the two tertiary N atoms (SUM1 and SUM2) and
      the parameter DeltaSUM (= SUM1 - SUM2) considered. It was found that in compounds
      with a considerable DeltaSUM value, the more pyramidal N atoms are usually
      oriented so that the corresponding lone electron pair is anti with respect to the
      P=O group. In (I), (II) and (III), the phosphoryl and carbonyl groups, separated
      by an N atom, are anti with respect to each other. In the C(O)NHP(O) fragment of
      (I)-(III), the P-N bond is longer and the O-P-N angle is contracted compared with
      the other two P-N bonds and the O-P-N angles in the molecules. These effects are
      also seen in analogous compounds deposited in the CSD. Compounds with
      [C(O)NH]P(O)[N]X (X ? N), such as compounds with a [C(O)NH]P(O)[N][O] skeleton,
      have not been considered here. Also, compounds with a [C(O)NH](2)P(O)[N] fragment
      have not been reported to date. In the crystal structures of all three title
      compounds, adjacent molecules are linked via pairs of P=O...H-N hydrogen bonds,
      forming dimers with C(i) symmetry.

PMID- 23007543
TI  - The effect of hydrogen bonding on the conformations of 2-(1H-indol-3-yl)-2
      oxoacetamide and 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide.
AB  - In the title compounds, C(10)H(8)N(2)O(2), (I), and C(12)H(12)N(2)O(2), (II), the
      two carbonyl groups are oriented with torsion angles of -149.3 (3) and -88.55
      (15) degrees , respectively. The single-bond distances linking the two carbonyl
      groups are 1.528 (4) and 1.5298 (17) A, respectively. In (I), the molecules are
      linked by an elaborate system of N-H...O hydrogen bonds, which form adjacent
      R(2)(2)(8) and R(4)(2)(8) ring motifs to generate a ladder-like construct.
      Adjacent ladders are further linked by N-H...O hydrogen bonds to build a three
      dimensional network. The hydrogen bonding in (II) is far simpler, consisting of
      helical chains of N-H...O-linked molecules that follow the 2(1) screw of the b
      axis. It is the presence of an elaborate hydrogen-bonding system in the crystal
      structure of (I) that leads to the different torsion angle for the orientation of
      the two adjacent carbonyl groups from that in (II).

PMID- 23007545
TI  - An irreversible phase transition in 1-n-butylindeno[2,1-c]pyran-3,9-dione.
AB  - At ambient temperature, the title compound, C(16)H(14)O(3), is triclinic, with
      the n-butyl side chain disordered in an out-of-plane orientation. On cooling
      below 240 K, it converts into a different triclinic phase with an ordered planar
      conformation and denser packing, which is retained on warming to room
      temperature. The transition (occasionally) proceeds from single crystal to single
      crystal.

PMID- 23007544
TI  - (E)-N'-(4-Chlorobenzylidene)-, (E)-N'-(4-bromobenzylidene)- and (E)-N'-[4
      (diethylamino)benzylidene]- derivatives of 4-hydroxybenzohydrazide.
AB  - The 4-chloro- [C(14)H(11)ClN(2)O(2), (I)], 4-bromo- [C(14)H(10)BrN(2)O(2), (II)]
      and 4-diethylamino- [C(18)H(21)N(3)O(2), (III)] derivatives of benzylidene-4
      hydroxybenzohydrazide, all crystallize in the same space group (P2(1)/c), (I) and
      (II) also being isomorphous. In all three compounds, the conformation about the
      C=N bond is E. The molecules of (I) and (II) are relatively planar, with dihedral
      angles between the two benzene rings of 5.75 (12) and 9.81 (17) degrees ,
      respectively. In (III), however, the same angle is 77.27 (9) degrees . In the
      crystal structures of (I) and (II), two-dimensional slab-like networks extending
      in the a and c directions are formed via N-H...O and O-H...O hydrogen bonds. The
      molecules stack head-to-tail via pi-pi interactions involving the aromatic rings
      [centroid-centroid distance = 3.7622 (14) A in (I) and 3.8021 (19) A in (II)]. In
      (III), undulating two-dimensional networks extending in the b and c directions
      are formed via N-H...O and O-H...O hydrogen bonds. The molecules stack head-to
      head via pi-pi interactions involving inversion-related benzene rings [centroid
      centroid distances = 3.6977 (12) and 3.8368 (11) A].

PMID- 23007546
TI  - Bis(4-methylphenylsulfonyl)amino 4-methylbenzenesulfonate: a new member of the
      (RSO2)ON(SO2R)2 family.
AB  - The title compound, C(21)H(21)NO(7)S(3), consists of an SO(2)ON(SO(2))(2) central
      fragment and three terminal 4-methylphenyl groups each attached at a sulfonyl S
      atom. The most obvious characteristic is the presence of two nearly face-to-face
      benzene rings, with their centroids separated by a rather short distance [3.7808
      (18) A], but with a rather slanted relative orientation [dihedral angle = 20.63
      (13) degrees ] so as to preclude a strong intramolecular pi-pi interaction. The
      third benzene ring is nearly perpendicular to the other two [dihedral angles =
      71.62 (14) and 70.4 (13) degrees ]. The packing of the structure is directed by
      two C-H...O hydrogen bonds involving aromatic H atoms (methyl H atoms are
      strictly non-interacting), which define chains running in the [100] direction.
      These one-dimensional chains evolve parallel to each other and exhibit no
      significant lateral interactions.

PMID- 23007547
TI  - Eight isostructural 4,4'-disubstituted N-phenylbenzenesulfonamides.
AB  - The isostructural crystals of 4-cyano-N-(4-methoxyphenyl)benzenesulfonamide,
      C(14)H(12)N(2)O(3)S, (I), N-(4-methoxyphenyl)-4
      (trifluoromethyl)benzenesulfonamide, C(14)H(12)F(3)NO(3)S, (II), 4-iodo-N-(4
      methoxyphenyl)benzenesulfonamide, C(13)H(12)INO(3)S, (III), 4-bromo-N-(4
      methoxyphenyl)benzenesulfonamide, C(13)H(12)BrNO(3)S, (IV), 4-chloro-N-(4
      methoxyphenyl)benzenesulfonamide, C(13)H(12)ClNO(3)S, (V), 4-fluoro-N-(4
      methoxyphenyl)benzenesulfonamide, C(13)H(12)FNO(3)S, (VI), N-(4-chlorophenyl)-4
      methoxybenzenesulfonamide, C(13)H(12)ClNO(3)S, (VII), and 4-cyano-N
      phenylbenzenesulfonamide, C(13)H(10)N(2)O(2)S, (VIII), contain infinite chains
      composed of N-H...O(sulfonyl) hydrogen-bonded molecules. The crystal structures
      of (I)-(VIII) have been compared using the XPac software and quantitative
      descriptors of isostructurality were generated [Gelbrich, Threlfall & Hursthouse
      (2012). CrystEngComm, 14, 5454-5464]. Certain isostructural relationships in this
      series involve molecules with substantially different spatial demands, e.g. (VI)
      and (VIII) are related by the simultaneous interchange of F->CN on the
      benzenesulfonamide ring and OMe->H on the N-phenyl ring, which indicates that the
      geometry of the three-dimensional crystal-packing mode of (I)-(VIII) is unusually
      adaptable to different molecular shapes.

PMID- 23007548
TI  - Three derivatives of 4-fluoro-5-sulfonylisoquinoline.
AB  - In 4-fluoroisoquinoline-5-sulfonyl chloride, C(9)H(5)ClFNO(2)S, (I), one of the
      two sulfonyl O atoms lies approximately on the isoquinoline plane as a result of
      minimizing the steric repulsion between the chlorosulfonyl group and the
      neighbouring F atom. In (S)-(-)-4-fluoro-N-(1-hydroxypropan-2-yl)isoquinoline-5
      sulfonamide, C(12)H(13)FN(2)O(3)S, (II), there are two crystallographically
      independent molecules (Z' = 2). The molecular conformations of these two
      molecules differ in that the amine group of one forms an intramolecular
      bifurcated hydrogen bond with the F and OH groups, whilst the other forms only a
      single intramolecular N-H...F hydrogen bond. The N-H...F hydrogen bonds
      correspond to weak coupling between the N(H) and (19)F nuclei, observed in the
      (1)H NMR solution-state spectra. In (S)-(-)-4-[(4-fluoroisoquinolin-5
      yl)sulfonyl]-3-methyl-1,4-diazepan-1-ium chloride, C(15)H(19)FN(3)O(2)S(+).Cl(-),
      (III), the isoquinoline plane is slightly deformed, suggestive of a steric effect
      induced by the bulky substituent on the sulfonyl group.

PMID- 23007549
TI  - Mapping the after-effects of theta burst stimulation on the human auditory cortex
      with functional imaging.
AB  - Auditory cortex pertains to the processing of sound, which is at the basis of
      speech or music-related processing. However, despite considerable recent
      progress, the functional properties and lateralization of the human auditory
      cortex are far from being fully understood. Transcranial Magnetic Stimulation
      (TMS) is a non-invasive technique that can transiently or lastingly modulate
      cortical excitability via the application of localized magnetic field pulses, and
      represents a unique method of exploring plasticity and connectivity. It has only
      recently begun to be applied to understand auditory cortical function. An
      important issue in using TMS is that the physiological consequences of the
      stimulation are difficult to establish. Although many TMS studies make the
      implicit assumption that the area targeted by the coil is the area affected, this
      need not be the case, particularly for complex cognitive functions which depend
      on interactions across many brain regions. One solution to this problem is to
      combine TMS with functional Magnetic resonance imaging (fMRI). The idea here is
      that fMRI will provide an index of changes in brain activity associated with TMS.
      Thus, fMRI would give an independent means of assessing which areas are affected
      by TMS and how they are modulated. In addition, fMRI allows the assessment of
      functional connectivity, which represents a measure of the temporal coupling
      between distant regions. It can thus be useful not only to measure the net
      activity modulation induced by TMS in given locations, but also the degree to
      which the network properties are affected by TMS, via any observed changes in
      functional connectivity. Different approaches exist to combine TMS and functional
      imaging according to the temporal order of the methods. Functional MRI can be
      applied before, during, after, or both before and after TMS. Recently, some
      studies interleaved TMS and fMRI in order to provide online mapping of the
      functional changes induced by TMS. However, this online combination has many
      technical problems, including the static artifacts resulting from the presence of
      the TMS coil in the scanner room, or the effects of TMS pulses on the process of
      MR image formation. But more importantly, the loud acoustic noise induced by TMS
      (increased compared with standard use because of the resonance of the scanner
      bore) and the increased TMS coil vibrations (caused by the strong mechanical
      forces due to the static magnetic field of the MR scanner) constitute a crucial
      problem when studying auditory processing. This is one reason why fMRI was
      carried out before and after TMS in the present study. Similar approaches have
      been used to target the motor cortex, premotor cortex, primary somatosensory
      cortex and language-related areas, but so far no combined TMS-fMRI study has
      investigated the auditory cortex. The purpose of this article is to provide
      details concerning the protocol and considerations necessary to successfully
      combine these two neuroscientific tools to investigate auditory processing.
      Previously we showed that repetitive TMS (rTMS) at high and low frequencies
      (resp. 10 Hz and 1 Hz) applied over the auditory cortex modulated response time
      (RT) in a melody discrimination task. We also showed that RT modulation was
      correlated with functional connectivity in the auditory network assessed using
      fMRI: the higher the functional connectivity between left and right auditory
      cortices during task performance, the higher the facilitatory effect (i.e.
      decreased RT) observed with rTMS. However those findings were mainly
      correlational, as fMRI was performed before rTMS. Here, fMRI was carried out
      before and immediately after TMS to provide direct measures of the functional
      organization of the auditory cortex, and more specifically of the plastic
      reorganization of the auditory neural network occurring after the neural
      intervention provided by TMS. Combined fMRI and TMS applied over the auditory
      cortex should enable a better understanding of brain mechanisms of auditory
      processing, providing physiological information about functional effects of TMS.
      This knowledge could be useful for many cognitive neuroscience applications, as
      well as for optimizing therapeutic applications of TMS, particularly in auditory
      related disorders.

PMID- 23007550
TI  - Few genes are associated with the capability of pancreatic ductal adenocarcinoma
      cells to grow in the liver of nude rats.
AB  - Owing to aggressiveness and chemoresistance, pancreatic ductal adenocarcinoma
      (PDAC) is characterised by a poor prognosis. To address this disease-spe-cific
      dilemma we aimed to establish animal models, which can be used for identifying
      new specific tumor markers, as well as serving as tools for potential therapeutic
      approaches. From a panel of sixteen pancreatic cancer cell lines, two human
      (Suit2-007 and Suit2-013) and a rat (ASML) cell line were selected for their
      properties to grow in the liver of male RNU rats and mimic liver metastasis of
      PDAC. For better monitoring of metastatic tumor growth in vivo, all three
      pancreatic cancer cell lines were stably transfected with eGFP and luciferase
      marker genes. In addition, the mRNA expression profile of 13 human PDAC cell
      lines was analyzed by BeadChip array analysis. Only 33 genes and 5 signaling
      pathways were identified as significantly associated with the ability of the cell
      lines to grow initially and/or consistently in rat liver. Only a minority of
      these genes (osteopontin, matrix metalloproteinase-1 and insulin-like growth
      factor 1) has been intensively studied and shown to be closely related to cancer
      progression. The function of the remaining 30 genes ranges from moderate to
      poorly investigated, and their function in cancer progression is still unclear.
      The ensuing three pancreatic cancer liver metastasis models vary in their
      aggressiveness and macroscopic growth. They will be used for preclinical
      evaluation of new therapeutic approaches aiming at the genes identified.

PMID- 23007551
TI  - Antitumor action of alpha(1)-adrenoceptor blockers on human bladder, prostate and
      renal cancer cells.
AB  - The present study investigated the antitumor action of alpha(1)-adrenoceptor
      blockers on human bladder, prostate and renal cancer cells. For bladder cancer
      cell lines used here such as 253J, 5637, KK-47, T24 and UM-UC-3 cells, prazosin,
      a selective alpha(1)-adrenoceptor blocker, reduced cell viability at
      concentrations more than 30 umol/l. Likewise, naftopidil, a blocker of alpha(1A)-
      and alpha(1D)-adrenoceptors, reduced cell viability for all the bladder cancer
      cells used here in a concentration (10-100 umol/l)-dependent manner, with a much
      greater advantage than prazosin. Naftopidil also reduced cell viability for human
      prostate cancer cell lines such as DU145, LNCap and PC-3 cells and ACHN human
      renal cancer cells, with a much higher potential than prazosin. Thus, the results
      of the present study suggest that naftopidil could be a beneficial antitumor drug
      for the treatment of urological cancers.

PMID- 23007552
TI  - Aldehyde dehydrogenase (ALDH) superfamily in plants: gene nomenclature and
      comparative genomics.
AB  - In recent years, there has been a significant increase in the number of
      completely sequenced plant genomes. The comparison of fully sequenced genomes
      allows for identification of new gene family members, as well as comprehensive
      analysis of gene family evolution. The aldehyde dehydrogenase (ALDH) gene
      superfamily comprises a group of enzymes involved in the NAD(+)- or NADP(+)
      dependent conversion of various aldehydes to their corresponding carboxylic
      acids. ALDH enzymes are involved in processing many aldehydes that serve as
      biogenic intermediates in a wide range of metabolic pathways. In addition, many
      of these enzymes function as 'aldehyde scavengers' by removing reactive aldehydes
      generated during the oxidative degradation of lipid membranes, also known as
      lipid peroxidation. Plants and animals share many ALDH families, and many genes
      are highly conserved between these two evolutionarily distinct groups.
      Conversely, both plants and animals also contain unique ALDH genes and families.
      Herein we carried out genome-wide identification of ALDH genes in a number of
      plant species-including Arabidopsis thaliana (thale crest), Chlamydomonas
      reinhardtii (unicellular algae), Oryza sativa (rice), Physcomitrella patens
      (moss), Vitis vinifera (grapevine) and Zea mays (maize). These data were then
      combined with previous analysis of Populus trichocarpa (poplar tree), Selaginella
      moellindorffii (gemmiferous spikemoss), Sorghum bicolor (sorghum) and Volvox
      carteri (colonial algae) for a comprehensive evolutionary comparison of the plant
      ALDH superfamily. As a result, newly identified genes can be more easily analyzed
      and gene names can be assigned according to current nomenclature guidelines; our
      goal is to clarify previously confusing and conflicting names and classifications
      that might confound results and prevent accurate comparisons between studies.

PMID- 23007553
TI  - Characterization of the stress-inducible OsNCED3 promoter in different transgenic
      rice organs and over three homozygous generations.
AB  - To be effective in crop biotechnology applications, gene promoters need to be
      stably active over sequential generations in a population of single-copy
      transgenic lines. Most of the stress-inducible promoters characterized in plants
      thus far have been analyzed at early (T0, T1 or T2) generations and/or by testing
      only a small number of transgenic lines. In our current study, we report our
      analysis of OsNCED3, a stress-inducible rice promoter involved in ABA
      biosynthesis, in various organs and tissues of transgenic rice plants over the
      T(2-4) homozygous generations. The transgene copy numbers in the lines harboring
      the OsNCED3:gfp construct were determined and six single- and two double-copy
      transgenic lines were analyzed for promoter activity in comparison with the
      Wsi18, a stress-inducible promoter previously characterized. The exogenous
      promoter activities were found to be significantly enhanced in the roots and
      leaves, whereas zero or low levels of activity were evident in grains and
      flowers, under drought and high-salinity conditions. The highest induction levels
      of gfp transcripts in the OsNCED3:gfp plants upon drought treatments were 161-
      and 93-fold in leaves and roots, respectively, and these levels were comparable
      with those of gfp transcripts in the Wsi18:gfp plants. A comparison of the
      promoter activities between the T2-T4 plants revealed that comparable activity
      levels were maintained over these three homozygous generations with no evidence
      of silencing. Thus, our results provide the OsNCED3 promoter that is stress
      inducible in a whole rice plant except for in the aleurones and endosperm and
      stably active over three generations.

PMID- 23007554
TI  - Phototropin 1 and cryptochrome action in response to green light in combination
      with other wavelengths.
AB  - Genetic studies have shown the effects of various photoreceptors on early
      photomorphogenic processes, defining the precise time course of red (RL), far-red
      (FrL) and blue light (BL) action. In this study, the effect of green wavebands in
      conjunction with these responses is examined. Longer-term (end point; 24-96 h)
      analysis of hypocotyl elongation in enriched green environments shows an increase
      in growth compared to seedlings under blue, red or both together. The effect was
      only observed at lower fluence rates (<10 MUmol/m2 s). Genetic analyses
      demonstrate that cryptochromes are required for this GL effect, consistent with
      earlier findings, and that the phy receptors have no influence. However, analysis
      of early (minutes to hours) stem growth kinetics indicates that GL cannot reverse
      the cryptochrome-mediated BL effect during early stem growth inhibition, and
      instead acts additively with BL to drive cryptochrome-mediated inhibition. Green
      light (GL) treatments antagonize RL and FrL-mediated hypocotyl inhibition. The GL
      opposition of RL responses persists in phyA, phyB, cry1cry2 and phot2 mutants.
      The response requires phot1 and NPH3, suggesting that this is not a GL response,
      but instead a response to extremely low-fluence rate BL. Tests with dim BL (<0.1
      MUmol/m2 s) confirm a previously uncharacterized phot1-dependent promotion of
      stem growth, opposing the effects of RL. These findings demonstrate how enriched
      green environments may adjust RL and BL photomorphogenic responses through both
      the crys and phot1 receptors, and define a new role for phot1 in stem growth
      promotion.

PMID- 23007555
TI  - Effect of ifenprodil on GluN1/GluN2B N-methyl-D-aspartate receptor gating.
AB  - Ifenprodil is an allosteric inhibitor of GluN1/GluN2B N-methyl-D-aspartate
      receptors. Despite its widespread use as a prototype for drug development and a
      subtype-selective tool for physiologic experiments, its precise effect on
      GluN1/GluN2B gating is yet to be fully understood. Interestingly, recent
      crystallographic evidence identified that ifenprodil, unlike zinc, binds at the
      interface of the GluN1/GluN2B amino terminal domain dimer by an induced-fit
      mechanism. To delineate the effect of this unique binding on GluN1/GluN2B
      receptor gating, we recorded steady-state currents from cell-attached and outside
      out patches. At pH 7.9 in cell-attached patches, ifenprodil increased the
      occupancy of the long-lived shut conformations, thereby reducing the open
      probability of the receptor with no change in the mean open time. In addition,
      ifenprodil selectively affected the area of shut time constants, but not the time
      constants themselves. Kinetic analyses suggested that ifenprodil prevents the
      transition of the receptor to an open state and increases its dwell time in an
      intrinsically occurring closed conformation or desensitized state. We found
      distinct differences in the action of ifenprodil at GluN1/GluN2B in comparison
      with previous studies on the effect of zinc on GluN1/GluN2A gating, which may
      arise due to their unique binding sites. Our data also uncover the potential pH
      dependent action of ifenprodil on gating. At a low pH (pH 7.4), but not pH 7.9,
      ifenprodil reduces the mean open time of GluN1/GluN2B receptors, which may be
      responsible for its usefulness as a context-dependent inhibitor in conditions
      like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.

PMID- 23007556
TI  - Computer-assisted design and rapid prototype modeling in microvascular mandible
      reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the use of computer-assisted design and rapid
      prototype modeling to improve the speed and accuracy of mandibular
      reconstruction. STUDY DESIGN: Case-control study. METHODS: Between 2005 and 2011,
      38 subjects underwent fibula free flap mandibular reconstruction using computer
      assisted design and rapid prototype modeling. Titanium plates were prebent using
      the models prior to surgery. Direct plate bending on the native mandible to
      accurately restore occlusion would not have been possible in 11 patients with
      exophytic tumors, nine patients with pathologic fractures, and 10 patients with a
      prior segmental mandibulectomy. Computer-generated cutting guides were utilized
      to facilitate fibular osteotomies. RESULTS: The mean operative time for subjects
      was 8.8 +/- 1.0 hours compared to the mean operative time defect-matched control
      group, for whom computer-assisted design and models were not used, of 10.5 +/-
      1.4 hours (P = .0006). Comparison of the preoperative and postoperative mandibles
      demonstrated that the mean change in position of selected bony landmarks
      (condyles, gonions, and gnathion) was less in the subject group than in the
      control group (4.11 +/- 3.09 mm vs. 6.92 +/- 5.64 mm, respectively; P = .001)
      Comparison of postoperative mandibles with preoperative virtual plans showed a
      mean deviation of 2.40 +/- 2.06 mm from planned fibular segment lengths and 3.51
      +/- 2.69 degrees  from planned angles between fibular segments. CONCLUSIONS:
      Computer-assisted design and rapid prototype modeling have the potential to
      increase the speed and accuracy of mandibular reconstruction. We believe these
      technologies are particularly useful for cases in which the original architecture
      of the mandible has been distorted or destroyed.

PMID- 23007557
TI  - The nerves to the plantaris muscle and a bipennate part of the soleus muscle.
AB  - We performed nerve fiber analysis of the nerve to the plantaris muscle in ten
      cases. Macroscopically, the nerve to the plantaris muscle has a tendency to
      branch off from the tibial nerve itself independent of the nerves to the
      gastrocnemius and soleus muscles (the triceps surae muscle). After removing the
      epineurium of the tibial nerve, it was revealed that, in all ten cases, the nerve
      to the plantaris muscle formed a common funicular trunk with the nerve to a
      bipennate part of the soleus. This trunk is akin to the nerves to the deep
      muscles of the calf. In addition, in five of the ten cases, the nerve to the
      plantaris muscle had another component, which arose from the branch to the
      popliteus muscle. By removing the perineurium of the nerves concerned, it became
      clear that the elements of the nerve to the plantaris muscle, and of the nerve to
      the bipennate part of the soleus, had an intimate relation (inseparable). On the
      other hand, the elements of the nerve to the plantaris muscle and those to the
      popliteus were separable and they showed different routes proximally. Based on
      the present findings derived from nerve fiber analysis, we postulate that the
      plantaris muscle and bipennate part of the soleus muscle were probably derived
      from the deep muscle anlage of the calf in spite of their topographical closeness
      to the superficial muscles of the calf.

PMID- 23007558
TI  - Cellular and molecular mechanisms of hepatocellular carcinoma: an update.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor that
      accounts for ~80 % of all liver cancer cases worldwide. It is a multifactorial
      disease caused by a variety of risk factors and often develops in the background
      of underlying cirrhosis. A number of cellular phenomena, such as tumor
      microenvironment, inflammation, oxidative stress, and hypoxia act in concert with
      various molecular events to facilitate tumor initiation, progression, and
      metastasis. The emergence of microRNAs and molecular-targeted therapies adds a
      new dimension in our efforts to combat this deadly disease. Intense research in
      this multitude of areas has led to significant progress in our understanding of
      cellular processes and molecular mechanisms that occur during multistage events
      that lead to hepatocarcinogenesis. In this review, we discuss the current
      knowledge of HCC, focusing mainly on advances that have occurred during the past
      5 years and on the development of novel therapeutics for liver cancer.

PMID- 23007560
TI  - The influence of chronic fluorosis on mitochondrial dynamics morphology and
      distribution in cortical neurons of the rat brain.
AB  - The present study was designed to evaluate the effects of chronic fluorosis on
      the dynamics (including fusion and fission proteins), fragmentation, and
      distribution of mitochondria in the cortical neurons of the rat brain in an
      attempt to elucidate molecular mechanisms underlying the brain damage associated
      with excess accumulation of fluoride. Sixty Sprague-Dawley rats were divided
      randomly into three groups of 20 each, that is, the untreated control group
      (drinking water naturally containing <0.5 mg fluoride/l, NaF), the low-fluoride
      group (whose drinking water was supplemented with 10 mg fluoride/l) and the high
      fluoride group (50 mg fluoride/l). After 6 months of exposure, the expression of
      mitofusin-1 (Mfn1), fission-1 (Fis1), and dynamin-related protein-1 (Drp1) at
      both the protein and mRNA levels were detected by Western blotting,
      immunohistochemistry, and real-time PCR, respectively. Moreover, mitochondrial
      morphology and distribution in neurons were observed by transmission electron or
      fluorescence microscopy. In the cortices of the brains of rats with chronic
      fluorosis, the level of Mfn1 protein was clearly reduced, whereas the levels of
      Fis1 and Drp1 were elevated. The alternations of expression of the mRNAs encoding
      all three of these proteins were almost the same as the corresponding changes at
      the protein levels. The mitochondria were fragmented and the redistributed away
      from the axons of the cortical neurons. These findings indicate that chronic
      fluorosis induces abnormal mitochondrial dynamics, which might in turn result in
      a high level of oxidative stress.

PMID- 23007559
TI  - Developmental immunotoxicity of ethanol in an extended one-generation
      reproductive toxicity study.
AB  - The susceptibility of developing immune system to chemical disruption warrants
      the assessment of immune parameters in reproductive and developmental testing
      protocols. In this study, a wide range of immune endpoints was included in an
      extended one-generation reproduction toxicity study (EOGRTS) design to determine
      the relative sensitivity of immune and developmental parameters to ethanol
      (EtOH), a well-known developmental toxicant with immunomodulatory properties.
      Adult Wistar rats were exposed to EtOH via drinking water (0, 1.5, 4, 6.5, 9,
      11.5 and 14 % (w/v EtOH)) during premating, mating, gestation and lactation and
      continuation of exposure of the F(1) from weaning until killed. Immune
      assessments were performed at postnatal days (PNDs) 21, 42 and 70. Keyhole limpet
      hemocyanin (KLH)-specific immune responses were evaluated following subcutaneous
      immunizations on PNDs 21 and 35. EtOH exposure affected innate as well as
      adaptive immune responses. The most sensitive immune parameters included white
      blood cell subpopulations, ConA-stimulated splenocyte proliferation, LPS-induced
      NO and TNF-alpha production by adherent splenocytes and KLH-specific immune
      responses. Most parameters showed recovery after cessation of EtOH exposure after
      weaning in the 14 % exposure group. However, effects on LPS-induced NO and TNF
      alpha production by adherent splenocytes and KLH-specific parameters persisted
      until PND 70. The results demonstrate the relative sensitivity to EtOH of
      especially functional immune parameters and confirm the added value of immune
      parameters in the EOGRTS. Furthermore, this study identified an expanded KLH
      specific parameter set and LPS-induced NO and TNF-alpha production by adherent
      splenocytes as valuable parameters that can provide additional information on
      functional immune effects.

PMID- 23007561
TI  - Synthesis, characterisation and adsorption properties of a porous copper(II) 3D
      coordination polymer exhibiting strong binding enthalpy and adsorption capacity
      for carbon dioxide.
AB  - The synthesis and characterisation of microporous coordination polymers
      containing copper(II) or cobalt(II) and 2-(pyridin-4-yl)malonaldehyde (Hpma) is
      described and the gas adsorption properties evaluated. Single-crystal X-ray
      structure determinations identified the structures as [M(pma)(2)].2X (M = Cu, 1;
      Co, 2; X = MeOH, MeCN), which contain 3D networks with rutile topology and
      continuous 1D rectangular channels with diameters ranging from 3 to 4 A. The
      materials exhibit low BET surface areas of 143 m(2) g(-1), but possess large
      capacities for carbon dioxide capture of 14.1 wt%. The small pore channels are
      shown to account for this, delivering a particularly strong binding enthalpy to
      adsorbed CO(2) of 38 kJ mol(-1), and a very large adsorption capacity relative to
      the low surface area.

PMID- 23007563
TI  - The (Mis)diagnosis of Creutzfeldt-Jakob Disease.

PMID- 23007562
TI  - Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using "click"
      chemistry.
AB  - A convergent synthesis of a novel estrogen receptor-targeted drug hybrid was
      developed based on structures of the potent anti-proliferative mitomycin C and
      the steroidal anti-estrogen RU 39411. The steroidal antiestrogen was prepared
      with an azido-triethylene glycoloxy linker while the mitomycin C derivative
      (porfirimycin) incorporated a complementary 7-N-terminal alkyne. The two
      components were ligated using the Huisgen [3 + 2] cycloaddition ("click")
      reaction. Preliminary biological assays demonstrated that the final hybrid
      compound retained both potent anti-estrogenic and anti-proliferative activities.

PMID- 23007570
TI  - Dietary influences on intestinal immunity.
AB  - The function of the gastrointestinal tract relies on a monolayer of epithelial
      cells, which are essential for the uptake of nutrients. The fragile lining
      requires protection against insults by a diverse array of antigens. This is
      accomplished by the mucosa-associated lymphoid tissues of the gastrointestinal
      tract, which constitute a highly organized immune organ. In this Review, we
      discuss several recent findings that provide a compelling link between dietary
      compounds and the organization and maintenance of immune tissues and lymphocytes
      in the intestine. We highlight some of the molecular players involved, in
      particular ligand-activated nuclear receptors in lymphoid cells.

PMID- 23007571
TI  - Tools to therapeutically harness the human antibody response.
AB  - The natural human antibody response is a rich source of highly specific,
      neutralizing and self-tolerant therapeutic reagents. Recent advances have been
      made in isolating and characterizing monoclonal antibodies that are generated in
      response to natural infection or vaccination. Studies of the human antibody
      response have led to the discovery of crucial epitopes that could serve as new
      targets in vaccine design and in the creation of potentially powerful
      immunotherapies. With a focus on influenza virus and HIV, herein we summarize the
      technological tools used to identify and characterize human monoclonal antibodies
      and describe how these tools might be used to fight infectious diseases.

PMID- 23007573
TI  - Impact of biomarkers on clinical trial risk in breast cancer.
AB  - We determined the success rate of new drug approval by the US FDA in two breast
      cancer indications, one of which used a biomarker. This allowed us to assess if
      biomarkers improved clinical trial risk in breast cancer. We performed a
      retrospective screening of industry-sponsored drug development programs
      registered on clinicaltrials.gov from 1998 to 2012 for HER2-positive patients
      compared to patients that had either failed or had been exposed to anthracycline
      or taxane, whose first phase I in this indication occurred no earlier than 1998.
      Compounds not registered on clinicaltrials.gov and studied exclusively outside
      the US were excluded. Twenty-nine drugs for HER2-positive patients and 28 drugs
      for anthracycline/taxane-exposed patients met our screening criteria. The overall
      success rate of new drug development in anthracycline/taxane patients was only 15
      %, while in HER2-positive patients it was 23 %. However, HER2-targeted therapies
      underperformed compared to broad acting agents. The cost for clinical trial
      testing alone, when adjusted for the risk of failure, for HER2-positive breast
      cancer patients was $199 million, significantly lower than the cost of $274
      million for anthracycline/taxane-experienced patients. The use of a validated
      biomarker, such as HER2, reduced clinical trial risk by as much as 50 % resulting
      in cost savings of 27 % in advanced and metastatic breast cancer. However, these
      data have to be evaluated in a context in which studies combining a novel drug
      with a novel biomarker not yet recognized by the FDA may actually increase
      clinical trial risk.

PMID- 23007572
TI  - The impact of probiotics and prebiotics on the immune system.
AB  - Probiotics and prebiotics are increasingly being added to foodstuffs with claims
      of health benefits. Probiotics are live microorganisms that are thought to have
      beneficial effects on the host, whereas prebiotics are ingredients that stimulate
      the growth and/or function of beneficial intestinal microorganisms. But can these
      products directly modulate immune function and influence inflammatory diseases?
      Here, Nature Reviews Immunology asks four experts to discuss these issues and
      provide their thoughts on the future application of probiotics as a disease
      therapy.

PMID- 23007574
TI  - Biochemical and pharmacological characterization of human c-Met neutralizing
      monoclonal antibody CE-355621.
AB  - The c-Met proto-oncogene is a multifunctional receptor tyrosine kinase that is
      stimulated by its ligand, hepatocyte growth factor (HGF), to induce cell growth,
      motility and morphogenesis. Dysregulation of c-Met function, through mutational
      activation or overexpression, has been observed in many types of cancer and is
      thought to contribute to tumor growth and metastasis by affecting mitogenesis,
      invasion, and angiogenesis. We identified human monoclonal antibodies that bind
      to the extracellular domain of c-Met and inhibit tumor growth by interfering with
      ligand-dependent c-Met activation. We identified antibodies representing four
      independent epitope classes that inhibited both ligand binding and ligand
      dependent activation of c-Met in A549 cells. In cells, the antibodies antagonized
      c-Met function by blocking receptor activation and by subsequently inducing
      downregulation of the receptor, translating to phenotypic effects in soft agar
      growth and tubular morphogenesis assays. Further characterization of the
      antibodies in vivo revealed significant inhibition of c-Met activity (>= 80%
      lasting for 72-96 h) in excised tumors corresponded to tumor growth inhibition in
      multiple xenograft tumor models. Several of the antibodies identified inhibited
      the growth of tumors engineered to overexpress human HGF and human c-Met (S114
      NIH 3T3) when grown subcutaneously in athymic mice. Furthermore, lead candidate
      antibody CE-355621 inhibited the growth of U87MG human glioblastoma and GTL-16
      gastric xenografts by up to 98%. The findings support published pre-clinical and
      clinical data indicating that targeting c-Met with human monoclonal antibodies is
      a promising therapeutic approach for the treatment of cancer.

PMID- 23007575
TI  - The expression of URGCP gene in prostate cancer cell lines: correlation with
      rapamycin.
AB  - Molecular targets in prostate cancer are continually being explored, for which
      there are currently few therapeutic options. Rapamycin (RPM) is an antifungal
      macrolide antibiotic isolated from Streptomyces hygroscopicus which can inhibit
      the G1 to S transition. URGCP (upregulator of cell proliferation) is a novel gene
      located on chromosome 7p13. We aimed to investigate the role of URGCP gene
      expression changes in PC3, DU145, and LNCAP cell lines with/out RPM. Average cell
      viability and cytotoxic effect of rapamycin were investigated at 24 h intervals
      for three days by using Trypan blue dye exclusion test and XTT assay. Cytotoxic
      effects of rapamycin in DU145, PC3 and LNCAP cells were detected in time and dose
      dependent manner with the IC(50) doses within the range of 1-100 nM. As the
      results were evaluated, IC(50) doses in the DU145, PC3, and LNCaP cells were
      detected as 10, 25, and 50 nM, respectively. The mean relative ratios of URGCP
      gene expression in DU145, LNCAP and PC3 cells were found as -1.48, 6.59 and 
      13.00, respectively, when compared to rapamycin-free cells. The False Discovery
      Rate adjusted p value in DU145, LNCAP and PC3 were 1.25 * 10(-5), 2.20 * 10(-8)
      and 6.20 * 10(-9), respectively. When the URGCP gene expression level is compared
      between the dose and control group, we found that URGCP gene expression was
      significantly decreased in dose groups of DU145 and PC3 cells.

PMID- 23007576
TI  - Histone deacetylase inhibitor BML-210 induces growth inhibition and apoptosis and
      regulates HDAC and DAPC complex expression levels in cervical cancer cells.
AB  - Histone deacetylase inhibitors (HDACIs) represent a new class of targeted anti
      cancer agents and different other diseases, like muscular disorders. A number of
      studies have shown that extracellular signal-activated kinases can target
      chromatin-modifying complexes directly and regulate their function. The molecular
      connection between the dystrophin-associated protein complex (DAPC) and chromatin
      has been described, by showing that NO signaling regulates histone deacetylase
      (HDAC) activity and influences gene expression in different cell types. In
      present study, we investigated HDACs changes in HeLa cells undergoing growth
      inhibition and apoptosis, caused by HDACI BML-210 and retinoic acid (ATRA). Cell
      cycle analysis indicated that HeLa cell treatment with 20 and 30 MUM
      concentration of BML-210 increased the proportion of cells in G0/G1 phase, and
      caused accumulation in subG1, indicating that the cells are undergoing apoptosis.
      We determined down-regulation of HDAC 1-5 and 7 after treatment with BML-210.
      Also, we demonstrated expression of different isoforms of alpha-dystrobrevin
      (alpha-DB) and other components of DAPC such as syntrophin, dystrophin, beta
      dystrobrevin (beta-DB) and NOS in HeLa cells after treatments. We determined
      changes in protein expression level of dystrophin, NOS1, alpha- and beta-DB and
      in subcellular localization of alpha-DB after treatments with BML-210 and ATRA.
      In conclusion, these results suggest that HDACI BML-210 can inhibit cell growth
      and induce apoptosis in cervical cancer cells, what correlates with down
      regulation of HDAC class I and II and changes in the DAPC expression levels. This
      can be important for identifying target proteins in DAPC signaling to HDACs, as a
      target of pharmacological intervention for treatment of muscular dystrophies and
      other diseases.

PMID- 23007577
TI  - Fluorescent measurement of [Ca2+]c: basic practical considerations.
AB  - There is a vast array of dyes currently available for measurement of cytosolic
      calcium. These encompass single and dual excitation and single and dual emission
      probes. The choice of particular probe depends on the experimental question and
      the type of equipment to be used. It is therefore extremely difficult to define a
      universal approach that will suit all potential investigators. Preparations under
      investigation are loaded with the selected organic indicator dye by incubation
      with ester derivatives, by micropipet injection or reverse permeabilization.
      Indicators can also be targeted to a range of intracellular organelles.
      Calibration of a fluorescent signal into Ca(2+) concentration is in theory
      relatively simple but the investigator needs to take great care in this process.
      This chapter describes the theory of these processes and some of the pitfalls
      users should be aware of. Precise experimental details can be found in the
      subsequent chapters of this volume.

PMID- 23007578
TI  - Measurement of [Ca2+]i in whole cell suspensions using Fura-2.
AB  - Use of Fura-2 in whole cell suspensions to measure changes in intracellular
      Ca(2+) is probably one of the simplest, yet most widely used protocols described
      in this volume. Whole cell suspensions are loaded with Fura-2 and then placed
      into a cuvette-based fluorimetric system (measuring 510 nm emission at
      alternating 340/340 nm excitation). Cells can be stimulated with agonists and
      antagonists to enable temporal response profiling and concentration-response
      curves to be constructed. The protocol can be used for a wide range of cells
      including those transfected with Ca(2+)-signaling proteins, e.g., receptors and
      channels. Loading characteristics and the need for agents to retain loaded dye
      (e.g., probenecid) need to be determined empirically. Calibration of whole cell
      suspensions to convert the fluorescent signal into Ca(2+) is simply performed
      using Triton-X lysis (to determine R (max)) and EGTA chelation (to determine R
      (min)).

PMID- 23007579
TI  - Confocal microscopy: theory and applications for cellular signaling.
AB  - The development of confocal microscopy and the commercial availability of
      confocal microscopes have provided many laboratories with an extremely powerful
      approach to examine cellular structure and function. Allied with the development
      of suitable tools, it is now possible to interrogate a wide range of structural
      and functional aspects on both fixed and live cells. Here we describe the basic
      principles underlying confocal microscopy and provide methodological accounts of
      how it can be used to study aspects related particularly (but not exclusively) to
      the expression, activation, and regulation of signaling by G-protein-coupled
      receptors. Specifically we provide detailed protocols for examining: the cellular
      expression and distribution of proteins by immunocytochemistry; cytoplasmic and
      organelle Ca(2+) signaling using fluorescent indicators; second messenger
      generation using fluorescently tagged biosensors; and ligand/receptor
      internalization using fluorescently tagged peptide agonists and receptors.

PMID- 23007581
TI  - Measuring Ca2+ changes in multiwell format using the Fluorometric Imaging Plate
      Reader (FLIPR((r))).
AB  - The Fluorometric Imaging Plate Reader (FLIPR) has made a significant contribution
      to drug discovery programs. The key advantage of FLIPR over conventional plate
      readers is the ability to measure fluorescence emission from multiple wells (96
      wells or 384 wells) simultaneously and with high temporal resolution.
      Consequently, FLIPR has been used extensively to record dynamic intracellular
      processes such as changes in intracellular Ca(2+) ion concentration, membrane
      potential, and pH. Since FLIPR is used to measure a functional response in cells,
      it is rapidly able to distinguish full agonists, partial agonists, and
      antagonists at a target of interest, making the system a valuable screening tool
      for interrogation of compound libraries. Automated FLIPR systems for ultra high
      throughput have also become available that employ integrated plate stackers,
      washers and specialized stages to allow users to shuttle cell and compound plates
      from incubators or storage magazines onto the FLIPR system itself. In this
      chapter generic methods for assessing intracellular Ca(2+) on the FLIPR are
      described.

PMID- 23007580
TI  - Ratiometric Ca2+ measurements using the FlexStation((r))Scanning Fluorometer.
AB  - The FlexStation( (r) ) Scanning Fluorometer is a fluorescence plate reader that
      can measure intracellular Ca(2+) concentration using both single-wavelength and
      dual-wavelength fluorescent probes. The FlexStation uses a Xenon flashlamp and
      monochromators for both excitation and emission light to allow the use of a wide
      range of fluorescent indicators. The system incorporates a fluid transfer system
      for addition of test compounds from a source plate to the cell plate during data
      acquisition. Both plates are contained within a temperature-controlled unit that
      can be controlled accurately between room temperature and 45 degrees C. The
      FlexStation can be configured to read a range of plate sizes. In this chapter
      generic methods for assessing intracellular Ca(2+) on the FlexStation using
      ratiometric dyes are described.

PMID- 23007582
TI  - Ratiometric [Ca2+]i measurements in adherent cell-lines using the NOVOstar
      microplate reader.
AB  - The control of free ionized intracellular calcium concentration ([Ca(2+)](i)) is
      an established mechanism of cellular activation, regulating a diverse range of
      cellular events. Consequentially, experimental measurement of [Ca(2+)](i) is a
      potent technique for the medical science laboratory. The NOVOstar microplate
      reader is a versatile system, which may be easily configured to measure
      [Ca(2+)](i). Moreover, the relatively low cost of this system makes it an
      attractive one for researchers adhering to a modest budget, whilst allowing
      medium throughput to be achieved.These methods serve as a starting point for
      researchers wishing to measure intracellular calcium concentration in adherent
      cell-lines using the NOVOstar plate reader. Briefly, adherent cells are seeded
      into well plates 1 day prior to calcium determinations being made. On the day of
      the experiment, autofluorescence values of individual wells of cells are
      determined prior to the cells being loaded with the fluorophore, fura-2.
      [Ca(2+)](i) determinations are acquired by activating a predefined program within
      the NOVOstar software; full parameters are provided within this chapter for this
      purpose. Fluorescence ratio values may be easily calibrated to give absolute
      intracellular calcium concentrations (nM). Calibration involves determining
      experimental fluorescence at calcium-saturating and calcium-free conditions;
      ionomycin and EGTA are used to produce these two conditions respectively.
      Finally, mathematical calculation of absolute intracellular calcium concentration
      is described by use of the Grynkiewicz equation.

PMID- 23007583
TI  - Whole-cell patch-clamp recording of voltage-sensitive Ca2+ channel currents in
      single cells: heterologous expression systems and neurones.
AB  - Voltage-sensitive calcium channels (VSCC) are vital to the normal physiology of
      many cell types, including neurones, skeletal, cardiac and smooth muscle cells,
      heart pacemaker tissue and endocrine cells. Whole-cell recording is a functional
      electrophysiological assay that allows real-time measurement of macroscopic VSCC
      activity at the level of single cells. Using this technique, it is possible to
      probe the molecular physiology, pharmacology, and biophysics of VSCC proteins
      with a level of precision rarely surpassed in cell biological studies. With best
      practice voltage-dependent gating behaviors of VSCCs can be interrogated with
      temporal resolution <100 ms. These advantages have commonly been exploited using
      recombinant channels heterologously expressed in cell-lines, where the molecular
      identity of the channel under study can be precisely defined, and also in native
      cell types freshly isolated from intact tissue using enzymes. The latter approach
      is especially valuable for study of adult brain neurons as these cells are not
      amenable to primary culture. We also describe a method with which VSCCs can be
      studied in nucleated macropatches derived from neurons without the use of
      enzymes. Although automated patch-clamp systems are now available they have
      limitations, and manual whole-cell recording of VSCC currents remains an expert
      technique requiring intelligent, conative experimentation.

PMID- 23007584
TI  - Combined calcium fluorescence recording with ionic currents in contractile cells.
AB  - Measurement of calcium (Ca(2+)) fluorescence in conjunction with ionic currents
      is of particular importance in contractile cells, such as cardiac ventricular
      myocytes and vascular smooth muscle. The interplay between membrane potential and
      intracellular calcium ([Ca(2+)](i)) is fundamental to the regulation of
      contractile function and cell signalling. Here the loading of cells either with
      an esterified fluorescence indicator prior to patch clamp recording, or dye
      loading via the patch pipette with "free" indicator, is described to allow
      simultaneous measurement of fluorescence and electrical signals.

PMID- 23007585
TI  - Measurement of phospholipase C by monitoring inositol phosphates using
      [3H]inositol labeling protocols in permeabilized cells.
AB  - Data on the production of inositol phosphates is a useful complement to
      measurements of intracellular Ca(2+). The basic principle is labeling of the
      inositol lipids by growing the appropriate cell line in culture in the presence
      of [3H]inositol for 2-3 days to reach labeling equilibrium. Lithium ions at 10 mM
      inhibits the degradation of inositol phosphates to free inositol and is used to
      trap the inositol in the inositol polyphosphate forms. Inositol phosphates can be
      separated with ease from free inositol by using anion exchange chromatography. A
      method capable of easily processing approximately 40-60 samples in a single day
      is presented.

PMID- 23007586
TI  - Single-cell imaging techniques for the real-time detection of IP3 in live cells.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) is a ubiquitous second messenger, derived
      from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP(2)) by enzymes
      of the phospholipase C (PLC) family. Binding of IP(3) to its cognate receptor in
      the endoplasmic reticulum membrane leads to release of Ca(2+) into the cytoplasm,
      which is involved in the regulation of an array of cellular functions.
      Traditional techniques for the detection of IP(3) have required the extraction of
      a large number of cells, with limitations in the time resolution of changes in
      IP(3) and an inability to obtain detailed information on the dynamics of this
      second messenger in single cells. Recent progress in this field has led to the
      development of a number of genetically encoded fluorescent biosensors, which upon
      recombinant expression are able selectively to detect real-time changes in IP(3)
      in single live cells. In this chapter, I detail protocols for the expression,
      visualization (by confocol or fluorescence microscopy), and interpretation of
      data obtained with such biosensors expressed in mammalian cells.

PMID- 23007587
TI  - Measurement of inositol(1,4,5)trisphosphate using a stereospecific radioreceptor
      mass assay.
AB  - Inositol(1,4,5)trisphosphate [Ins(1,4,5)P(3)] is an important second messenger
      that activates its cognate Ins(1,4,5)P(3) receptor to release Ca(2+) from
      intracellular stores. The assay described in this chapter uses the Ins(1,4,5)P(3)
      receptor (essentially as a binding protein) to measure the biologically active
      trisphosphate (specifically from other trisphosphates). The binding protein
      (Ins(1,4,5)P3 receptor) is prepared from Bovine adrenal glands and this is mixed
      with [(3)H]-labeled and unlabeled (generated from biological samples or
      standards) Ins(1,4,5)P(3). Using the same principles as for
      radioimmunoassay/ELISA the mass of Ins(1,4,5)P(3) in biological samples can be
      estimated.

PMID- 23007588
TI  - Measurement of [Ca2+]i in smooth muscle strips using front-surface fluorimetry.
AB  - Changes in the cytosolic Ca(2+) concentrations ([Ca(2+)](i)) play a primary role
      in the regulation of the contraction of smooth muscle cells. However, the
      relationship between [Ca(2+)](i) and tension exhibits a temporal change during
      the time course of contraction or relaxation. The extent of the tension
      development for a given change in [Ca(2+)](i) also varies depending on the type
      of contraction and relaxation. Therefore, it is essential to measure [Ca(2+)](i)
      and tension simultaneously in order to determine the molecular and cellular
      mechanisms in both the regulation of contraction and relaxation of smooth muscle.
      This chapter provides the basic principles of the technique of front-surface
      fluorimetry as well as the protocols and tips for the simultaneous measurement of
      [Ca(2+)](i) and tension in the smooth muscle tissues with use of fura-2 or Fura
      PE3 as fluorescent Ca(2+) indicators. The loading of sufficient amount of the
      Ca(2+) indicators in smooth muscles is essential for the successful measurement
      of [Ca(2+)](i) with minimum optical artifacts. The protocol gives our practice
      for the loading of the Ca(2+) indicators in various smooth muscle tissues.

PMID- 23007589
TI  - Calcium measurements from whole heart using Rhod-2.
AB  - Calcium recording from whole heart is an important technique to investigate role
      of calcium in cardiac arrhythmias. Intracellular calcium can be recorded from
      multiple locations using imaging devices and organic dyes or genetic probe
      (Tallini et al. PNAS 103(12):4753-4758, 2006) from whole heart. Here, we describe
      the optical apparatus and the method to record intracellular calcium transients.

PMID- 23007590
TI  - Measurement of changes in endothelial and smooth muscle Ca2+ in pressurized
      arteries.
AB  - The use of single- and dual-wavelength Ca(2+)-sensitive fluorescent dyes to
      monitor changes in endothelial and/or smooth muscle intracellular Ca(2+) levels
      has provided information linking Ca(2+) events to changes in arterial function.
      Here we describe the in vitro techniques used to selectively load Ca(2+)
      indicators into either the endothelium or the smooth muscle of cannulated rat
      cremaster arteries. These vessels normally develop spontaneous myogenic tone that
      is largely unaffected by the loading of Ca2+ indicators or the subsequent imaging
      procedures. This suggests that there is minimal Ca2+ buffering or damage, and
      that the fluorescent indicator-loaded vessels behave similarly to unloaded
      preparations. Importantly, these approaches are applicable to both isobaric and
      isometric preparations and have been also used for the study of a number of
      vascular beds including cerebral, mesenteric, coronary, and skeletal muscle
      vasculatures.

PMID- 23007591
TI  - Single cell and subcellular measurements of intracellular Ca2+ concentration.
AB  - Increases in bulk average cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) are
      derived from the combined activities of many Ca(2+) channels. Near (<100 nm) the
      mouth of each of these channels the local [Ca(2+)](c) rises and falls more
      quickly and reaches much greater values than occurs in the bulk cytoplasm. Even
      during apparently uniform, steady-state [Ca(2+)] increases large local
      inhomogeneities exist near channels. These local increases modulate processes
      that are sensitive to rapid and large changes in [Ca(2+)] but they cannot easily
      be visualized with conventional imaging approaches. The [Ca(2+)] changes near
      channels can be examined using total internal reflection fluorescence microscopy
      (TIRF) to excite fluorophores that lie within 100 nm of the plasma membrane. TIRF
      is particularly powerful when combined with electrophysiology so that ion channel
      activity can be related simultaneously to the local subplasma membrane and bulk
      average [Ca(2+)](c). Together these techniques provide a better understanding of
      the local modulation and control of Ca(2+) signals.

PMID- 23007592
TI  - Simultaneous analysis of intracellular pH and Ca2+ from cell populations.
AB  - Although changes in both pH(in) and [Ca(2+)](i) have been observed in response to
      a variety of agonists, it is not clear whether these ionic events work
      independently or are coordinated to lead to a specific physiological response.
      One of the fundamental problems in studying these ionic events is that changes in
      pH(in) modify Ca(2+) regulatory mechanisms and changes in Ca(2+) may modify pH
      regulation. It is desirable to use a technique that allows concomitant monitoring
      of these two ions in cell populations with high time resolution. Furthermore,
      like many Ca(2+) binding proteins, all Ca(2+)-sensitive fluoroprobes are
      inherently sensitive to pH owing to competition of H(+) for the Ca(2+)-binding
      sites. This chapter describes experimental paradigms that provide optimum
      conditions for simultaneous measurement of pH from the fluorescence emission of
      snarf-1, and Ca(2+) using fura-2. The fluorescence spectra of these compounds are
      sufficiently different to allow simultaneous measurement of pH and Ca(2+) both in
      vitro and in vivo. Moreover, the ratio of the H(+)-sensitive wavelengths of snarf
      1 is unaffected by Ca(2+), or the concomitant presence of fura-2 in cells.
      Although the fluorescence ratio of fura-2 is insensitive to the presence of snarf
      1, it is affected by pH, as indicated above. We describe procedures to correct
      for this effect and to obtain calibration parameters for fura-2 and snarf-1
      required to facilitate analysis of pH and Ca(2+) concentrations within cell
      populations.

PMID- 23007593
TI  - Measurements of Ca2+ concentration with recombinant targeted luminescent probes.
AB  - In the last two decades the study of Ca(2+) homeostasis in living cells has been
      enhanced by the explosive development of genetically encoded Ca(2+)-indicators.
      The cloning of the Ca(2+)-sensitive photoprotein aequorin and of the green
      fluorescent protein (GFP) from the jellyfish Aequorea victoria has been
      enormously advantageous. As polypeptides, aequorin and GFP allow their endogenous
      production in cell systems as diverse as bacteria, yeast, slime molds, plants,
      and mammalian cells. Moreover, it is possible to specifically localize them
      within the cell by including defined targeting signals in the amino acid
      sequence. These two proteins have been extensively engineered to obtain several
      recombinant probes for different biological parameters, among which Ca(2+)
      concentration reporters are probably the most relevant. The GFP-based Ca(2+)
      probes and aequorin are widely employed in the study of intracellular Ca(2+)
      homeostasis. The new generation of bioluminescent probes that couple the Ca(2+)
      sensitivity of aequorin to GFP fluorescence emission allows real-time
      measurements of subcellular Ca(2+) changes in single cell imaging experiments and
      the video-imaging of Ca(2+) concentrations changes in live transgenic animals
      that express GFP-aequorin bifunctional probes.

PMID- 23007594
TI  - Chimeric G proteins in fluorimetric calcium assays: experience with opioid
      receptors.
AB  - High throughput calcium mobilization assays are extensively used for
      pharmacological characterization of GPCR ligands. These approaches, initially
      developed for G(q)-coupled receptors, can be extended to G(i) coupled GPCRs using
      chimeric G proteins. Here we used the Galpha(qi5) protein to force the
      nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor, as well as the classical
      opioid receptors to signal through the PLC-IP(3)-Ca(2+) pathway in CHO cells.
      Calcium levels were monitored using the fluorometric imaging plate reader
      FlexStation II and the Ca(2+) dye Fluo 4 AM. For investigating the pharmacology
      of the NOP receptor a panel of full and partial agonists and antagonists were
      assessed, while a small panel of agonists and antagonists was used for evaluating
      the pharmacological profile of opioid receptors. Some limitations of this assay
      and differences in the results obtained in comparison with those with G(i) based
      biochemical assays are described. Overall, the present results confirm that the
      chimeric G protein strategy is useful for studying the pharmacological activity
      of G(i) coupled receptor ligands and that the aberrant signaling does not produce
      any measurable change in the pharmacological profile of the receptor under study.
      Thus, this G protein strategy is extremely useful for setting up primary
      screening assays for NOP and classical opioid receptors and likely for other
      members of the GPCR family.

PMID- 23007595
TI  - Compartmentalizing genetically encoded calcium sensors.
AB  - Within single cells there is a complex myriad of signaling which controls
      physiological process many of which are modulated, or signaled directly, by
      intracellular calcium ions. Understanding the exquisitely sensitive, and
      spatially restricted, changes in calcium has been of interest to the researcher
      for a number of years. Recent advances in this field have been driven by the
      development of genetically encoded calcium probes for detecting calcium changes
      within the cells specifically targeting organelles such as mitochondria,
      endoplasmic reticulum, and the nucleus. In this chapter the authors outline some
      of the available fluorescent probes, with particular emphasis on an endoplasmic
      reticulum targeted calcium biosensor in cell signaling studies with astrocytes,
      detailing experimental protocols and the interpretation of data from such probes.

PMID- 23007596
TI  - Measurement of cytosolic-free Ca2+ in plant tissue.
AB  - A range of techniques have been used to measure the concentration of cytosolic
      free Ca(2+) ([Ca(2+)](cyt)) in plant cells. Fluorescent Ca(2+)-sensitive
      indicators have been used extensively to measure plant [Ca(2+)](cyt) and a number
      of techniques are available for loading these into plant cells. Here we describe
      a method for measuring [Ca(2+)](cyt) in the guard cells of the model plant
      species Commelina communis by ratio photometry and imaging techniques using the
      ratiometric fluorescent Ca(2+)-sensitive indicator fura-2.

PMID- 23007597
TI  - Measurement of Ca2+-ATPase activity (in PMCA and SERCA1).
AB  - Ca(2+)-ATP pumps (those on the plasma membrane; PMCA and sarcoplasmic reticulum;
      SERCA1) have an important role to play in the regulation of intracellular calcium
      concentrations. In this chapter, three preparations, two membranes and a purified
      enzyme, best suited for studies of Ca(2+)-ATPase activity are described. The two
      selected membranes are the human red blood cell (RBC) ghosts, a representative of
      plasma membranes (PM), and the rabbit skeletal muscle SR, an intracellular
      membrane. In this protocol, Pi released during the ATPase reaction is
      subsequently measured colorimetrically as a complex of molybdovanadate. The
      method is simple (one-step), fast, sensitive, and reliable.

PMID- 23007598
TI  - Enhancement of extracellular electron transfer and bioelectricity output by
      synthetic porin.
AB  - The microbial fuel cell (MFC), is a promising environmental biotechnology for
      harvesting electricity energy from organic wastes. However, low bacterial
      membrane permeability of electron shuttles is a limiting factor that restricts
      the electron shuttle-mediated extracellular electron transfer (EET) from bacteria
      to electrodes, thus the electricity power output of MFCs. To this end, we
      heterologously expressed a porin protein OprF from Pseudomonas aeruginosa PAO1
      into Escherichia coli, which dramatically increased its membrane permeability,
      delivering a much higher current output in MFCs than its parental strain (BL21).
      We found that the oprF-expression strain showed more efficient EET than its
      parental strain. More strikingly, the enhanced membrane permeability also
      rendered the oprF-expression strain an efficient usage of riboflavin as the
      electron shuttle, whereas its parental strain was incapable of. Our results
      substantiated that membrane permeability is crucial for the efficient EET, and
      indicated that the expression of synthetic porins could be an efficient strategy
      to enhance bioelectricity generation by microorganisms (including electrogenic
      bacteria) in MFCs.

PMID- 23007599
TI  - Methods for diversity and overlap analysis in T-cell receptor populations.
AB  - The paper presents some novel approaches to the empirical analysis of diversity
      and similarity (overlap) in biological or ecological systems. The analysis is
      motivated by the molecular studies of highly diverse mammalian T-cell receptor
      (TCR) populations, and is related to the classical statistical problem of
      analyzing two-way contingency tables with missing cells and low cell counts. The
      new measures of diversity and overlap are proposed, based on the information
      theoretic as well as geometric considerations, with the capacity to naturally up
      weight or down-weight the rare and abundant population species. The consistent
      estimates are derived by applying the Good-Turing sample-coverage correction. In
      particular, novel consistent estimates of the Shannon entropy function and the
      Morisita-Horn index are provided. Data from TCR populations in mice are used to
      illustrate the empirical performance of the proposed methods vis a vis the
      existing alternatives. 

PMID- 23007600
TI  - Mathematical modeling of viral infection dynamics in spherical organs.
AB  - A general mathematical model of viral infections inside a spherical organ is
      presented. Transported quantities are used to represent external cells or viral
      particles that penetrate the organ surface to either promote or combat the
      infection. A diffusion mechanism is considered for the migration of transported
      quantities to the organ inner tissue. Cases that include the effect of
      penetration, diffusion and proliferation of immune system cells, the generation
      of latently infected cells and the delivery of antiviral treatment are analyzed.
      Different antiviral mechanisms are modeled in the context of spatial variation.
      Equilibrium conditions are also calculated to determine the radial profile after
      the infection progresses and antiviral therapy is delivered for a long period of
      time. The dynamic and equilibrium solutions obtained in this paper provide
      insight into the temporal and spatial evolution of viral infections. 

PMID- 23007601
TI  - A dysphoric-like state during early withdrawal from extended access to
      methamphetamine self-administration in rats.
AB  - RATIONALE: Negative emotional states during drug withdrawal may contribute to
      compulsive drug intake and seeking in humans. Studies suggest that extended
      access to methamphetamine induces compulsive drug intake in rats. OBJECTIVE: The
      present study tested the hypothesis that compulsive methamphetamine intake in
      rats with extended access is associated with negative emotional states during
      drug withdrawal. METHODS: Rats with short (1 h, ShA) and extended access (6 h,
      LgA) to methamphetamine self-administration (0.05 mg/kg/infusion) were tested for
      reward thresholds using intracranial self-stimulation (ICSS). Different groups of
      ShA and LgA rats were examined for depression-like and anxiety-like states in the
      novelty-suppressed feeding, open field, defensive burying, and forced swim tests.
      RESULTS: With extended access, ICSS thresholds gradually increased, which was
      correlated with the increase of drug intake. During drug withdrawal, the
      increased ICSS thresholds returned to levels observed before exposure to extended
      access to methamphetamine. Upon re-exposure to extended access to
      methamphetamine, ICSS thresholds showed a more rapid escalation than during the
      initial exposure. LgA rats showed a longer latency to approach chow in the center
      of a novel field and remained immobile longer in the forced swim test than ShA
      rats did during early withdrawal. In contrast, ShA rats actively buried an
      aversive shock probe whereas LgA rats remained immobile in the defensive burying
      test. CONCLUSION: The data suggest that extended access to methamphetamine
      produces a more depressive-like state than anxiety-like state in rats during
      early withdrawal.

PMID- 23007602
TI  - Measurement of alcohol hangover severity: development of the Alcohol Hangover
      Severity Scale (AHSS).
AB  - OBJECTIVE: This study aims to develop a new alcohol hangover symptom severity
      scale and compare its effectiveness with the Hangover Symptoms Scale (HSS), the
      Acute Hangover Scale (AHS), and a one-item hangover score. METHODS: Data from
      1,410 Dutch students (Penning et al., Alcohol Alcohol 47:248-252, 2012) on the
      severity of 47 hangover symptoms were re-analyzed to develop the Alcohol Hangover
      Severity Scale (AHSS). The psychometric properties of the AHSS were compared with
      those of the HSS and the AHS. A survey among 1,000 students compared the AHSS and
      HSS with a one-item hangover severity score. The AHSS was further tested in a
      naturalistic hangover experiment. RESULTS: The 12 items of the AHSS were fatigue,
      clumsiness, dizziness, apathy, sweating, shivering, nausea, heart pounding,
      confusion, stomach pain, concentration problems, and thirst. The Penning et al.
      (Alcohol Alcohol 47:248-252, 2012) data revealed that the predictive validity of
      the AHSS (92.4 %) for the overall hangover score was significantly higher than
      that of the HSS (81.5 %) and the AHS (71.0 %). The survey data (N = 966) showed
      that scores on the AHSS (39.7 %) and the HSS (47.6 %) only moderately predicted
      the one-item hangover score. A total of 119 subjects completed the naturalistic
      study. On average, they consumed 9.7 alcoholic consumptions, yielding a mean
      estimated blood alcohol concentration (BAC) of 0.16 %. During hangover, the AHSS
      score correlated significantly with the number of alcoholic consumptions (r =
      0.38, p < 0.0001) and estimated BAC (r = 0.40, p < 0.0001). CONCLUSIONS: The AHS,
      HSS, and AHSS all seem appropriate for application in hangover research. The use
      of a one-item hangover scale is not recommended.

PMID- 23007603
TI  - Responsiveness to reward following cessation of smoking.
AB  - RATIONALE AND OBJECTIVES: It has been suggested that stopping smoking may lead to
      reduced responsiveness to rewarding stimulation. We assessed such changes in
      dependent smokers who abstained from smoking continuously for 4 weeks. METHODS:
      Eight hundred seventy-four consecutive smokers treated at a UK Clinic provided
      ratings of changes in their perception of rewarding events at 1 and 4 weeks after
      their target quit date. Measurements included the Enjoyment of Life Questionnaire
      (EOL) and Mood and Physical Symptoms Scale (a measure of withdrawal discomfort).
      Self-reports of continuous abstinence were verified by expired air carbon
      monoxide readings. RESULTS: In 585 participants who were continuously abstinent
      for the first week and provided EOL ratings, there was an increase in positive
      reactions to rewarding events compared to reactions while smoking (t = 5.9, p <
      0.001). In 192 participants who were continuously abstinent for 4 weeks and
      provided ratings at both 1 and 4 weeks, there was a further significant increase
      in positive reactions (F(1,191) = 18.71, p < 0.001). More severe withdrawal
      discomfort was related to decreased enjoyment of rewarding events. CONCLUSIONS:
      Responsiveness to reward increases within a week of stopping smoking and it
      increases further after 4 weeks of abstinence. The finding has implications for
      reassuring smokers worried about post-quitting mood changes.

PMID- 23007605
TI  - Efficient synthesis of N-(buta-2,3-dienyl) amides from terminal N-propargyl
      amides and their synthetic potential towards oxazoline derivatives.
AB  - A series of N-allenyl amides was prepared conveniently from N-propargyl amides in
      good to excellent yields via a modified procedure developed in this group. The
      palladium-catalyzed coupling-cyclization of these prepared N-allenyl amides in
      the presence of organic iodides has been developed affording the oxazoline
      derivatives efficiently.

PMID- 23007604
TI  - Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal
      gray matter on cannabidiol chronic effects in panic-like responses in rats.
AB  - RATIONALE: Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis
      sativa plant that promotes antianxiety and anti-panic effects in animal models
      after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration.
      However, the effects of CBD repeated administration, and the possible mechanisms
      involved, in animal models of anxiety- and panic-related responses remain poorly
      understood. OBJECTIVE: The present study evaluates the role of the serotonergic
      neurotransmission within the DPAG in the modulation of escape responses of rats
      chronically treated with CBD. METHODS: Male Wistar rats received acute or
      repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the
      elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on
      facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter
      aim, we verified if these effects would be prevented by intra-DPAG injection of
      the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 MUL). Also, we verified,
      by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT)
      release and, by quantitative polymerase chain reaction, if there are changes in
      5HT-1A or 5HT-2C mRNA expression in DPAG. RESULTS: The results showed that
      repeated but not acute peripheral administration of CBD decreases escape
      responses in the ETM, suggesting a panicolytic effect. This treatment did not
      change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin
      extracellular concentrations in the DPAG. CBD effects were prevented by DPAG
      injection of the 5-HT1A receptor antagonist. CONCLUSIONS: Together, these
      findings suggest that repeated treatment with CBD induces anti-panic effects by
      acting on 5-HT1A receptors in DPAG.

PMID- 23007606
TI  - Covariation of copy number located at 16q22.1: new evidence in mammary ductal
      carcinoma.
AB  - Copy number variation (CNV) is crucial for gene regulation in humans. A number of
      studies have revealed that CNV contributes to the initiation and progression of
      cancer. In this study, we analysed four breast cancer cell lines and six fresh
      frozen tissues from patients to evaluate the CNV present in the genome using
      microarray-based comparative genomic hybridization (aCGH). Six genes located at
      16q22.1 were analysed by real-time PCR. The real-time PCR analysis revealed that
      the loss of CDH1/E2F4 may be associated with worse clinical and pathological
      findings. Interestingly, covariation of CDH1, CDH3, CTCF and E2F4 was found to be
      associated with triple negative breast cancer and HER-2 receptor status. In
      conclusion, our study supports the idea that CNV at 16q22.1 in breast cancer is a
      frequent event; furthermore, it reveals the covariation of CDH1, CDH3, CTCF and
      E2F4. The role of the covariation is more complex than a simple additive effect
      of these four separate genes, which may provide a novel target for breast cancer.

PMID- 23007607
TI  - Establishment of a bioluminescent imaging-based in vivo leukemia model by intra
      bone marrow injection.
AB  - In vivo leukemia mouse models are usually generated by intraperitoneal (IP) or
      intravenous (IV) injection of leukemia cells. However, the pattern of leukemia
      development observed can be inconsistent. This study investigated injection
      directly into bone marrow [intra-bone marrow transplantation (IBMT)], the natural
      microenvironment of leukemia. A bioluminescent imaging-based leukemia animal
      model has been established by direct injection of a bioluminescent leukemia cells
      (CCRF-CEM/fLuc) into NOD/SCID mouse tibia bone marrow and compared with models
      established by IP and IV routes. The comparison revealed that a bioluminescent in
      vivo leukemia model established via IBMT could recapitulate leukemia more
      faithfully and facilitate improved quantification of leukemia engraftment
      kinetics with a wider range of bioluminescent intensity than IP or IV. IBMT of
      bioluminescent leukemic cells allowed quantification of dose-dependent responses
      to anti-leukemic drugs, thus validating this model as a potential preclinical
      anti-leukemic drug screening system. IBMT-leukemia cells isolated from peripheral
      blood of the model mice and then injected into new recipients successfully
      established a second generation IBMT in vivo model and demonstrated the
      reproducibility of the model. Bioluminescent imaging-based analysis of this IBMT
      leukemia model could provide a means for the comprehensive evaluation of
      treatment responses with enhanced sensitivity in preclinical studies.

PMID- 23007608
TI  - Time-lapse imaging of neuroblast migration in acute slices of the adult mouse
      forebrain.
AB  - There is a substantial body of evidence indicating that new functional neurons
      are constitutively generated from an endogenous pool of neural stem cells in
      restricted areas of the adult mammalian brain. Newborn neuroblasts from the
      subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to
      their final destination in the olfactory bulb (OB). In the RMS, neuroblasts
      migrate tangentially in chains ensheathed by astrocytic processes using blood
      vessels as a structural support and a source of molecular factors required for
      migration. In the OB, neuroblasts detach from the chains and migrate radially
      into the different bulbar layers where they differentiate into interneurons and
      integrate into the existing network. In this manuscript we describe the procedure
      for monitoring cell migration in acute slices of the rodent brain. The use of
      acute slices allows the assessment of cell migration in the microenvironment that
      closely resembling to in vivo conditions and in brain regions that are difficult
      to access for in vivo imaging. In addition, it avoids long culturing condition as
      in the case of organotypic and cell cultures that may eventually alter the
      migration properties of the cells. Neuronal precursors in acute slices can be
      visualized using DIC optics or fluorescent proteins. Viral labeling of neuronal
      precursors in the SVZ, grafting neuroblasts from reporter mice into the SVZ of
      wild-type mice, and using transgenic mice that express fluorescent protein in
      neuroblasts are all suitable methods for visualizing neuroblasts and following
      their migration. The later method, however, does not allow individual cells to be
      tracked for long periods of time because of the high density of labeled cells. We
      used a wide-field fluorescent upright microscope equipped with a CCD camera to
      achieve a relatively rapid acquisition interval (one image every 15 or 30 sec) to
      reliably identify the stationary and migratory phases. A precise identification
      of the duration of the stationary and migratory phases is crucial for the
      unambiguous interpretation of results. We also performed multiple z-step
      acquisitions to monitor neuroblasts migration in 3D. Wide-field fluorescent
      imaging has been used extensively to visualize neuronal migration. Here, we
      describe detailed protocol for labeling neuroblasts, performing real-time video
      imaging of neuroblast migration in acute slices of the adult mouse forebrain, and
      analyzing cell migration. While the described protocol exemplified the migration
      of neuroblasts in the adult RMS, it can also be used to follow cell migration in
      embryonic and early postnatal brains.

PMID- 23007609
TI  - Piezoelectric BoneScalpel osteotomies in osteocutaneous free flaps.

PMID- 23007610
TI  - Thermodynamics of the interaction of ruthenium(III) polyaminecarboxylate
      complexes with bio-relevant ligands. Deactivation of the complexes as NO
      scavengers by thiol ligands.
AB  - The acid-base and complex-formation equilibria of [Ru(H(2)dtpa)(H(2)O)], where
      dtpa = diethylenetriaminepentaacetate, with a series of bio-relevant ligands
      having various functional groups, viz. thiol, amine, imidazole and carboxylate,
      were investigated using potentiometric and spectrophotometric techniques. The
      pK(a) values for [Ru(H(2)dtpa)(H(2)O)] were found to be 2.28 and 3.48 for the
      uncoordinated carboxylic acid groups and 8.83 for the coordinated water molecule.
      The complexes formed are of 1:1 stoichiometry and their formation-constants were
      determined. The effect of dioxane on the acid-base and complex-formation
      equilibria of the Ru(III) complex was studied. The displacement reaction of
      coordinated NO by the investigated ligands showed that thiols can compete with NO
      in their reaction with [Ru(III)(dtpa)(H(2)O)](2-). The results reveal that the
      Ru(III) complex is deactivated as a NO scavenger by thiolate ligands.

PMID- 23007611
TI  - Stroke from acute cervical internal carotid artery occlusion: treatment results
      and predictors of outcome.
AB  - BACKGROUND: Previous studies have not distinguished patients with acute cervical
      internal carotid artery (ICA) occlusions from those with intracranial occlusions
      and often consider them together in the same cohort. OBJECTIVES: To evaluate the
      outcomes of patients with stroke from acute cervical ICA occlusion treated with
      intravenous thrombolysis or primary endovascular procedures and to identify early
      predictors of functional recovery among these patients. DESIGN: Retrospective
      study. SETTING: Academic hospital. PATIENTS: We studied patients with ischemic
      stroke who received intravenous thrombolysis or endovascular treatment for acute
      cervical ICA occlusion at St Mary's Hospital, Mayo Clinic, Rochester, Minnesota.
      We evaluated the associations of vascular risk factors, severity of stroke,
      arterial recanalization, presence of tandem occlusions, and collateral distal
      flow with functional recovery at 90 days after stroke. MAIN OUTCOME MEASURES:
      Favorable functional recovery (Modified Rankin Scale score, 0-2). RESULTS: We
      identified 21 patients (median age, 67 years; median National Institutes of
      Health Stroke Scale score at presentation, 13), of whom 13 patients received
      intravenous thrombolysis and 8 patients underwent primary endovascular treatment.
      Three patients who received intravenous thrombolysis underwent rescue
      endovascular treatment. Favorable functional recovery (Modified Rankin Scale
      score, 0-2) was observed in 7 patients who received intravenous thrombolysis and
      in 1 patient who underwent primary endovascular treatment. Good collateral distal
      flow and intracranial tandem occlusions were observed in 6 patients and 12
      patients, respectively. Good collateral distal flow, observed more frequently in
      cigarette smokers, was associated with favorable functional recovery (odds ratio,
      20; 95% CI, 2-242; P = .02). CONCLUSIONS: Intravenous thrombolysis should be
      administered as first-line treatment in patients with early acute cervical ICA
      occlusion. Treatment benefits are accentuated in patients with better collateral
      circulation.

PMID- 23007613
TI  - Hyperthyroidism secondary to disseminated mucormycosis in a child with acute
      lymphoblastic leukemia: case report and a review of published reports.
AB  - Thyroiditis due to fungal infection is an extremely rare cause of
      hyperthyroidism. The most common etiological factor of thyroiditis is
      Aspergillus. Infections due to members of the Mucorales have been an increasing
      clinical problem in recent years, and the prognosis in generalized infections due
      to those fungi is usually very poor. No hyperthyroidism in a child with
      thyroiditis due to mucormycosis has been reported in the literature so far. We
      describe a clinical course of generalized mucormycosis with thyroid involvement
      in a 12-year-old girl treated for acute lymphoblastic leukemia. The child
      underwent a hyperthyroidism connected with thyroid involvement due to a fungal
      process. The diagnosis was based on the clinical signs, laboratory findings and
      typical ultrasound scan; however, later attempt to amplify the fungi DNA from the
      tissue block has failed. The child died because of multiorgan failure due to
      general fungal infection 49 days after the invasive fungal infection was
      diagnosed. The generalized mucormycosis is always connected with poor prognosis
      and the mortality is high.

PMID- 23007616
TI  - Glomerular diseases: podocyte hypertrophy mismatch and glomerular disease.

PMID- 23007617
TI  - Subclinical AKI--an emerging syndrome with important consequences.
AB  - According to guidelines published by Kidney Disease: Improving Global Outcomes,
      patients at risk of acute kidney injury (AKI) should be managed according to
      their susceptibilities and exposures. Clinical evaluation of a patient's risk of
      acute loss of renal function is of undisputed importance. However, such
      evaluations can be hindered by the complex presentations of critically ill
      patients and the lack of methods to detect early kidney damage. In this regard, a
      tool for diagnosis and stratification of patients at risk of AKI would complement
      clinical assessments and enable improved therapeutic decision-making. Emerging
      evidence suggests that 15-20% of patients who do not fulfil current serum
      creatinine-based consensus criteria for AKI are nevertheless likely to have acute
      tubular damage, which is associated with adverse outcomes. This evidence supports
      reassessment of the concept and evolution of the definition of AKI to incorporate
      biomarkers of tubular damage.

PMID- 23007619
TI  - Lupus nephritis: guidelines for lupus nephritis--more recommendations than data?

PMID- 23007621
TI  - Anaemia: Does the KDIGO guideline move the needle in CKD anaemia?

PMID- 23007622
TI  - Anandamide enhances expression of heat shock protein 72 to protect against
      ischemia-reperfusion injury in rat heart.
AB  - Anandamide (AEA), one of endocannabinoids, has been reported to exhibit a
      cardioprotective ability to limit the damage produced by ischemia-reperfusion
      injury. AEA reportedly enhanced heat shock protein 72 (HSP72) and HSP25
      expression in lungs to protect against lung inflammation. This study tested the
      hypothesis that intravenously injected AEA would induce HSP72 in the heart and
      thus render cardioprotection against ischemia-reperfusion injury in rats. Cardiac
      expression of HSPs was quantitatively evaluated in rats by Western blot analysis.
      That intravenously injected AEA 1 mg/kg in vivo induced expression of HSP72,
      which peaked at 24 h after administration. The enhancement of HSP72 by AEA was
      blocked by cannabinoid 2 (CB(2)) receptor antagonist AM630, but not cannabinoid 1
      (CB(1)) receptor antagonist AM251. Therefore, the rats were induced with a 30-min
      coronary occlusion followed by a 120-min reperfusion in vivo at 24 h after
      administration of drugs or vehicle, and then the infarct size was measured. AEA
      reduced myocardial infarct size compared to control group. Pretreatment with
      AM630 but not AM251 abolished the infarct size-limiting effect of AEA. Further
      study demonstrated pretreatment with phosphatidylinositol 3-kinase (PI3K)
      inhibitor wortmannin, Akt inhibitor MK-2206 and AM630 attenuated phosphorylation
      of Akt and AEA-induced HSP72 expression. The results suggest that AEA is
      cardioprotective against ischemia-reperfusion insult through its induction of
      HSP72, which might be mediated by the PI3K/Akt signaling pathway. These effects
      were mediated by CB(2) but not CB(1) receptors.

PMID- 23007623
TI  - Angiotensin II induced differentially expressed microRNAs in adult rat cardiac
      fibroblasts.
AB  - Angiotensin II (Ang II) plays a pivotal role in cardiac fibrosis, and microRNAs
      (miRNAs) have been shown to participate in diverse pathological processes. Our
      aim is to identify the Ang II-induced miRNAs in cardiac fibroblasts (CFs). The
      miRNA array was used to analyze the miRNA expression profile in CFs treated by
      Ang II and control cells. Stem-loop real-time PCR was performed to re-measure the
      levels of the differentially expressed miRNAs. Analysis of miRNA arrays showed
      that 33 miRNAs were differentially expressed (13 up- and 20 downregulated) in
      response to Ang II (100 nM) for 24 h as compared to control cells. Quantitative
      PCR revealed that Ang II upregulated the levels of miR-132, -125b-3p and miR-146b
      but downregulated the levels of miR-300-5p, -204* and miR-181b in CFs. The trend
      of miRNA change is consistent with microarray and qRT-PCR. Bioinformatic analysis
      revealed that MMP9 as the target of miR-132, MMP16 as the target of miR-146b and
      TIMP3 as the target of miR-181b have been listed in the miR database with
      experimentally validated targets, indicating the potential role of those miRNAs
      in cardiac fibrosis. Our results demonstrated that we did identify a subset of
      miRNAs that was differentially expressed in Ang II-treated CFs, which provide a
      starting point to explore their potential roles in cardiac fibrosis and
      hypertension.

PMID- 23007624
TI  - Oxytocin: a therapeutic target for mental disorders.
AB  - We review here that oxytocin (OT) is released into blood and within distinct
      brain regions in response to stressful and social stimuli, and has been shown to
      have an antidepressant-like effect in animal studies. Clinical reports suggest OT
      to be a promising drug for psychiatric diseases such as depression, anxiety
      disorders, schizophrenia, and autism. OT may also have therapeutic potential in
      the treatment of major depressive disorders, even though OT administered into
      blood does not readily cross the blood-brain barrier. Physiological functions
      such as sexual activity and mating induce the release of OT in the central
      nervous system. A drug for the treatment of sexual dysfunction, sildenafil,
      enhances the electrically evoked release of OT from the posterior pituitary. This
      drug has antidepressant-like effects through activation of an OT signaling
      pathway. These results suggest that sildenafil may have promise as a potential
      antidepressant.

PMID- 23007625
TI  - An unusual finding on a pelvic radiograph.

PMID- 23007626
TI  - More outsourcing of public services could save L22.6bn a year, says Confederation
      of British Industry.

PMID- 23007627
TI  - Serco admits it changed GPs' out of hours performance data 252 times.

PMID- 23007628
TI  - Breaking resistance: is there still a reason for clopidogrel in acute STEMI? :
      editorial to: "prasugrel versus high dose clopidogrel to overcome early high on
      clopidogrel platelet reactivity in patients with ST elevation myocardial
      infarction" by D. Alexopoulos et al.

PMID- 23007629
TI  - Aha! experiences leave a mark: facilitated recall of insight solutions.
AB  - The present study investigates a possible memory advantage for solutions that
      were reached through insightful problem solving. We hypothesized that insight
      solutions (with Aha! experience) would be remembered better than noninsight
      solutions (without Aha! experience). 34 video clips of magic tricks were
      presented to 50 participants as a novel problem-solving task, asking them to find
      out how the trick was achieved. Upon discovering the solution, participants had
      to indicate whether they had experienced insight during the solving process.
      After a delay of 14 days, a recall of solutions was conducted. Overall, 55 % of
      previously solved tricks were recalled correctly. Comparing insight and
      noninsight solutions, 64.4 % of all insight solutions were recalled correctly,
      whereas only 52.4 % of all noninsight solutions were recalled correctly. We
      interpret this finding as a facilitating effect of previous insight experiences
      on the recall of solutions. 

PMID- 23007630
TI  - Low-level visible light (LLVL) irradiation promotes proliferation of mesenchymal
      stem cells.
AB  - Low-level visible light irradiation was found to stimulate proliferation
      potential of various types of cells in vitro. Stem cells in general are of
      significance for implantation in regenerative medicine. The aim of the present
      study was to investigate the effect of low-level light irradiation on the
      proliferation of mesenchymal stem cells (MSCs). MSCs were isolated from the bone
      marrow, and light irradiation was applied at energy densities of 2.4, 4.8, and
      7.2 J/cm(2). Illumination of the MSCs resulted in almost twofold increase in cell
      number as compared to controls. Elevated reactive oxygen species and nitric oxide
      production was also observed in MSCs cultures following illumination with
      broadband visible light. The present study clearly demonstrates the ability of
      broadband visible light illumination to promote proliferation of MSCs in vitro.
      These results may have an important impact on wound healing. 

PMID- 23007631
TI  - The impact of a transjugular intrahepatic portosystemic shunt on the
      pharmacokinetics of caspofungin in a critically ill patient.
AB  - BACKGROUND: Caspofungin is the first echinocandin approved for the treatment of
      invasive fungal infections (IFI). As it is also well tolerated in patients with
      liver cirrhosis, caspofungin is an alternative for azoles in the treatment of IFI
      in patients with hepatic insufficiency. METHODS: We report, for the first time,
      the pharmacokinetics (PK) of caspofungin in a patient with Child A cirrhosis and
      a transjugular intrahepatic portosystemic shunt (TIPS) and compare values to
      previously published results. RESULTS: Caspofungin plasma levels were determined
      on days 14 (before TIPS reduction) and 29 (after TIPS reduction) of treatment.
      Troughs and peaks were 3.55 and 3.34 mg/l on day 14 and 9.28 and 9.49 mg/l on day
      29, resulting in, (1) PK parameters only slightly higher than previously reported
      results in healthy volunteers and patients with Child A liver cirrhosis without
      TIPS and (2) similar exposures before versus after TIPS reduction. This limited
      increase in exposure is not expected to be correlated to toxicity. CONCLUSION:
      Caspofungin is a safe alternative for azoles when treating patients with TIPS
      suffering from IFI.

PMID- 23007632
TI  - Limitations in health care access and utilization among long-term survivors of
      adolescent and young adult cancer.
AB  - BACKGROUND: Health care outcomes for long-term survivors of adolescent and young
      adult (AYA) cancer were compared with young adults without a cancer history,
      using the 2009 Behavioral Risk Factor Surveillance System data. METHODS: Eligible
      participants were 20 to 39 years of age. There were N = 979 who self-reported a
      cancer diagnosis between the ages of 15 to 34 years and were at least 5 years
      from diagnosis (excluding nonmelanoma skin cancer). The remaining 67,216
      participants with no cancer history were used as controls. Using multivariable
      regressions, relative risks and 95% confidence intervals were generated to
      examine the relationship of survivor status on indicators of poor health care
      (uninsured, no personal health care provider, no routine care, and avoiding
      seeing a doctor due to cost). Adjusted proportions were calculated by demographic
      groups. Results are weighted by Behavioral Risk Factor Surveillance System survey
      design. RESULTS: Although the proportion uninsured did not differ (21% of
      survivors vs 23% of controls), AYA survivors reported forgoing care due to cost
      at higher levels than controls (relative risk = 1.67, 95% CI = 1.44-1.94). Cost
      barriers were particularly high for survivors aged 20 to 29 years (44% vs 16% of
      controls; P < .001) and female survivors (35% vs 18% of controls; P < .001).
      Survivors reporting poorer health had more cost barriers. Moreover, uninsured
      survivors tended to report lower use of health care than did controls.
      CONCLUSIONS: AYA cancer survivors may forgo health care due to cost barriers,
      potentially inhibiting the early detection of late effects. Expanding health
      insurance coverage for young cancer survivors may be insufficient without
      adequate strategies to reduce their medical cost burdens.

PMID- 23007633
TI  - You're the doctor.

PMID- 23007634
TI  - Downregulation of protein kinase CK2 induces autophagic cell death through
      modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells.
AB  - Glioblastoma multiforme is the most common primary brain tumor and one of the
      most aggressive types of cancer in adults. Survival signaling and apoptosis
      resistance are hallmarks of malignant glioma cells. However, recent studies have
      shown that other types of cell death such as autophagy can be induced in
      malignant glioma cells. This suggests that stimulation of this process may be
      explored in new therapeutic strategies against glioblastoma multiforme. Protein
      kinase CK2 is a highly conserved and constitutively active enzyme that promotes
      numerous cellular processes such as survival, proliferation and differentiation.
      CK2 has been found elevated in several malignancies including brain tumors, and
      to confer resistance against chemotherapeutic agents and apoptotic stimuli.
      Recently, we have shown that the siRNA-mediated downregulation of CK2 leads to
      cell death in DNA-PK-proficient human glioblastoma cells. We show, here, that
      lack of CK2 results in significant induction of autophagic cell death in two
      human glioblastoma cell lines, M059K and T98G, as indicated by the positive
      staining of cells with the acidotropic dye acridine orange, and the specific
      recruitment of microtubule-associated protein 1 light chain 3 (LC3) to
      autophagosome membranes. Induction of autophagy is accompanied by CK2-dependent
      decreased phosphorylation of p70 ribosomal S6 and AKT kinases and significantly
      reduced expression levels of Raptor. In contrast, phosphorylation and activity
      levels of ERK1/2 are enhanced suggesting an inhibition of the PI3K/AKT/mTORC1 and
      activation of the ERK1/2 pathways. Furthermore, siRNA-mediated silencing of CK2
      results in increased mitochondrial superoxide production in both glioblastoma
      cell lines. However, mitochondrial reactive oxygen species release correlates
      with induction of autophagy only in T98G cells. Taken together, our findings
      identify CK2 as a novel component of the autophagic machinery and underline the
      potential of its downregulation to kill glioblastoma cells by overcoming the
      resistance to multiple anticancer agents.

PMID- 23007636
TI  - Synthesis of [PdL(NH3)2](PF6)2 (L = 1,1'-di(alkyl)-3,3'-methylenediimidazolin
      2,2'-diylidene) complexes and their reactivities towards N-donors.
AB  - The reaction of neutral palladium complexes PdLBr2 (L = 1,1'-di(alkyl)-3,3'
      methylenediimidazolin-2,2'-diylidene) with NH4PF6 in CH3CN afforded
      [PdL(NH3)2](PF6)2 (1-3, L1, alkyl = Me; L2, alkyl = Et; L3, alkyl = iso-Pr) and
      [PdL4(CH3CN)2](PF6)2 (4, alkyl = Mes). Treatment of [PdL(NH3)2](PF6)2 complexes
      with N-donors, 9-ethyl-3,6-diimidazolyl-carbazole (dicz), mercaptopyridine
      (HSPy), 3,5-dimethyl-1H-pyrazole (Hdmpz), and 1,2-dibenzoylhydrazine (H2dbhz)
      resulted in the substitution of NH3 forming dinuclear palladium complexes
      [PdL1(dicz)]2(PF6)4 (5), [PdL1(SPy)]2(PF6)2 (6), [PdL2(dmpz)]2(PF6)2 (7),
      [(PdL2)2(dbhz)] (8). Reaction of [PdL2(NH3)2](PF6)2 with hydrazine led to a
      mixture of [Pd(L2)2](PF6)2 (9) and [PdL2(NH2N=C(CH3)NHNH2)](PF6)2 (10). The
      NH2N=C(CH3)NHNH2 moiety was formed in situ by nucleophilic addition to CH3CN by
      two molecules of NH2NH2 and subsequent NH3 elimination. All of these complexes
      have been fully characterized by ESI-MS, NMR spectroscopy, and elemental
      analysis. The molecular structures of 1 and 5-10 were also studied by X-ray
      diffraction analysis.

PMID- 23007635
TI  - A new purification method for enhancing the immunogenicity of heat shock protein
      70-peptide complexes.
AB  - When purified from a tumor, certain heat shock protein 70 (HSP70)-peptide
      complexes (PCs) can function as effective vaccines against the tumor from which
      the complexes were isolated. The immunogenic mechanisms of HSP70 preparations
      imply that tumor-derived HSP70-PCs exhibit antigens associated with antigen
      presenting cells such as dendritic cells (DCs), inducing antigen-specific
      cytotoxic CD8+ T cells. However, some important membrane-resident tumor
      associated peptides, such as the HER-2/neu (c-erbB2) oncogenic protein, cannot be
      purified from HSP70 by traditional methods. In the present study, a new approach
      for the purification of HSP70-PCs from HER-2-overexpressing breast cancer cells
      was established. The detergent 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate (CHAPS) was used to obtain more effectual tumor peptides. The
      new purified product was named HSP70-HER-2-PC, and its immunological activities
      were determined. Traditionally purified HSP70-PCs (without CHAPS) and recombinant
      human HSP70-HER-2 protein complexes (recombined in vitro) were used as controls.
      These three HSP70-associated tumor antigenic complex pulsed dendritic cells (DCs)
      were used to stimulate an antitumor response. The mature DCs pulsed with HSP70
      HER-2-PCs stimulated autologous T cells to secrete higher levels of type I
      cytokine compared to the two control groups. Moreover, DCs pulsed with HSP70-HER
      2-PCs induced the most specific CD8+ T cells that specifically killed the same
      tumor cells. These findings provide a basis for new approaches in enhancing HSP70
      based immunotherapy for HER-2-associated or other membrane antigenic peptide
      related cancers.

PMID- 23007637
TI  - Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application
      to new radiotracers for NR2B NMDA receptor visualization.
AB  - In order to develop a novel and useful building block for the development of
      radiotracers for positron emission tomography (PET), we studied the
      radiolabelling of 1,4-disubstituted 3-[(18)F]fluoropiperidines. Indeed, 3
      fluoropiperidine became a useful building block in medicinal chemistry for the
      pharmacomodulation of piperidine-containing compounds. The radiofluorination was
      studied on substituted piperidines with electron-donating and electron
      withdrawing N-substituents. In the instance of electron-donating N-substituents
      such as benzyl or butyl, configuration retention and satisfactory fluoride-18
      incorporation yields up to 80% were observed. In the case of electron-withdrawing
      N-substituents leading to carbamate or amide functions, the incorporation yields
      depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building
      block was applied to the automated radiosynthesis of NR2B NMDA receptor
      antagonists and effected by a commercially available radiochemistry module. The
      in vivo evaluation of three radiotracers demonstrated minimal brain uptakes
      incompatible with the imaging of NR2B NMDA receptors in the living brain.
      Nevertheless, moderate radiometabolism was observed and, in particular, no
      radiodefluorination was observed which demonstrates the stability of the 3
      position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3
      [(18)F]fluoropiperidine moiety could be of value in the development of other
      radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists
      failed to demonstrate satisfactory properties for PET imaging of this receptor.

PMID- 23007639
TI  - Sex, stroke, and atrial fibrillation.
AB  - CONTEXT: Stroke is a serious complication associated with atrial fibrillation
      (AF). Women with AF are at higher risk of stroke compared with men. Reasons for
      this higher stroke risk in women remain unclear, although some studies suggest
      that undertreatment with warfarin may be a cause. OBJECTIVE: To compare
      utilization patterns of warfarin and the risk of subsequent stroke between older
      men and women with AF at the population level. DESIGN, SETTING, AND PATIENTS:  
      Population-based cohort study of patients 65 years or older admitted to the
      hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007,
      using administrative data with linkage between hospital discharge, physicians,
      and prescription drug claims databases. MAIN OUTCOME MEASURES:   Risk of stroke.
      RESULTS: The cohort comprised 39 398 men (47.2%) and 44 115 women (52.8%). At
      admission, women were older and had a higher CHADS2 (congestive heart failure,
      hypertension, age >=75 years, diabetes mellitus, prior stroke or transient
      ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001).
      At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin
      prescription. In adjusted analysis, women appeared to fill more warfarin
      prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001).
      Adherence to warfarin treatment was good in both sexes. Crude stroke incidence
      was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person
      years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven
      by the population of patients 75 years or older. In multivariable Cox regression
      analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14
      [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid
      conditions, individual components of the CHADS2 score, and warfarin treatment.
      CONCLUSION: Among older patients admitted with recently diagnosed AF, the risk of
      stroke was greater in women than in men, regardless of warfarin use.

PMID- 23007640
TI  - Fluorescent in situ hybridization on mitotic chromosomes of mosquitoes.
AB  - Fluorescent in situ hybridization (FISH) is a technique routinely used by many
      laboratories to determine the chromosomal position of DNA and RNA probes. One
      important application of this method is the development of high-quality physical
      maps useful for improving the genome assemblies for various organisms. The
      natural banding pattern of polytene and mitotic chromosomes provides guidance for
      the precise ordering and orientation of the genomic supercontigs. Among the three
      mosquito genera, namely Anopheles, Aedes, and Culex, a well-established
      chromosome-based mapping technique has been developed only for Anopheles, whose
      members possess readable polytene chromosomes. As a result of genome mapping
      efforts, 88% of the An. gambiae genome has been placed to precise chromosome
      positions. Two other mosquito genera, Aedes and Culex, have poorly polytenized
      chromosomes because of significant overrepresentation of transposable elements in
      their genomes. Only 31 and 9% of the genomic supercontings have been assigned
      without order or orientation to chromosomes of Ae. aegypti and Cx.
      quinquefasciatus, respectively. Mitotic chromosome preparation for these two
      species had previously been limited to brain ganglia and cell lines. However,
      chromosome slides prepared from the brain ganglia of mosquitoes usually contain
      low numbers of metaphase plates. Also, although a FISH technique has been
      developed for mitotic chromosomes from a cell line of Ae. aegypti, the
      accumulation of multiple chromosomal rearrangements in cell line chromosomes
      makes them useless for genome mapping. Here we describe a simple, robust
      technique for obtaining high-quality mitotic chromosome preparations from
      imaginal discs (IDs) of 4th instar larvae which can be used for all three genera
      of mosquitoes. A standard FISH protocol is optimized for using BAC clones of
      genomic DNA as a probe on mitotic chromosomes of Ae. aegypti and Cx.
      quinquefasciatus, and for utilizing an intergenic spacer (IGS) region of
      ribosomal DNA (rDNA) as a probe on An. gambiae chromosomes. In addition to
      physical mapping, the developed technique can be applied to population
      cytogenetics and chromosome taxonomy/systematics of mosquitoes and other insect
      groups.

PMID- 23007642
TI  - Expression of anion exchangers in cultured human endolymphatic sac epithelia.
AB  - HYPOTHESIS: Pendrin acts as a Cl-/HCO3- exchanger and is responsible for
      endolymphatic fluid volume and pH homeostasis in human endolymphatic sac
      epithelial cells. BACKGROUND: The endolymphatic sac (ES) is part of the
      membranous labyrinth in the inner ear that plays an important role in maintaining
      homeostasis of the endolymphatic fluid system. However, the exact mechanism of
      fluid volume and pH regulation is not fully understood yet. We aimed to
      demonstrate the expression of various anion exchangers (AEs), including pendrin,
      in cultured human endolymphatic sac epithelial (HESE) cells. METHODS:
      Endolymphatic sac specimens were harvested during acoustic neuroma surgery (n =
      24) using the translabyrinthine approach and then subcultured with high epidermal
      growth factor (EGF) (25 ng/ml) media and differentiated using low-EGF (0.5 ng/ml)
      media. The cultured cells were classified according to the morphology on TEM. The
      Cl-/HCO3- exchanger activity was assessed by pHi measurement using pH sensitive
      dye 2', 7'-bis (2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF/AM). We performed
      reverse transcriptase-polymerase chain reaction and immunohistochemical staining
      for AEs. RESULTS: We determined that 7.3 +/- 6.7% of cells differentiated into
      mitochodria-rich cells and 50.2 +/- 15.1 of cells differentiated into ribosome
      rich cells. bAE3, AE4, SLC26A4, SLC26A6, and SLC26A11 were also expressed in
      cultured HESE cells. The cultured cells had Cl-/HCO3- and Cl-/formate exchange
      activity on the luminal membrane, which is sensitive to anion channel inhibitors
      (DIDS 500 MUM). Furthermore, we showed that pendrin (SLC26A4) was expressed in
      cultured HESE cell membranes. CONCLUSION: Our results suggest that AEs, including
      pendrin, are expressed in epithelia of ES and may have role in maintaining ionic
      homeostasis, and the HESE culture system are useful for uncovering the functional
      role of ES epithelial cells.

PMID- 23007641
TI  - Up-regulation of Che-1 relates to neuronal apoptosis after traumatic brain injury
      in adult rats.
AB  - Che-1, a recently identified apoptosis related protein, affects the fate of
      various cell types when under stress. One attractive biological function of Che-1
      is promoting the transcription of p53 after DNA damage; besides, it can also
      regulate cell cycle via interacting with retinoblastoma protein. Although
      previous evidence has showed its anti-apoptotic role in cancer cells, some
      studies point out that Che-1 might play an opposite role in central nervous
      system (CNS). However, the function of Che-1 in CNS is still with limited
      acquaintance. To investigate whether Che-1 is involved in CNS lesion, we
      performed a traumatic brain injury model in adult rats. Up-regulation of Che-1
      was observed in the peritrauma brain cortex by performing western blotting and
      immunohistochemistry. Terminal deoxynucleotidyl transferase deoxy-UTP nick-end
      labeling and 4',6-diamidino-2-phenylindole staining suggested that Che-1 was
      involved in neuronal apoptosis after brain injury. We also investigated co
      localization of Che-1 and active-caspase-3 in the ipsilateral brain cortex. In
      addition, the expression patterns of p53, Bax and PCNA were parallel with that of
      Che-1. Besides this, neurotrophin receptor-interacting MAGE homolog was found to
      be associated with Che-1 after brain trauma. Based on our data, we suggested that
      Che-1 might play an important role in neuronal apoptosis following TBI; and might
      provide a basis for the further study on its role in regulating the expression of
      p53 and cell cycle re-entry in traumatic brain injury.

PMID- 23007643
TI  - Effects of hyperbaric oxygen and dexamethasone on proinflammatory cytokines of
      rat cochlea in noise-induced hearing loss.
AB  - HYPOTHESIS: To investigate effects of dexamethasone and hyperbaric oxygen therapy
      (HBOT) on proinflammatory cytokines and hearing levels in the noise-exposed
      cochlea of rats. BACKGROUND: There is an arising concern about negative effects
      of early initiation of HBOT on hearing in noise-induced hearing loss.
      Furthermore, effects of HBOT and dexamethasone on cochlear cytokines are not
      fully elucidated. METHODS: Twenty-six rats were divided into 3 groups: control,
      noise, and treatment groups. Five rats served as control group. White noise at
      115 dB sound pressure level was applied to the noise group of 4 rats for 10 days.
      This group was assigned to a positive control group as it was equivalent to
      treatment groups. The treatment group of 17 rats underwent the same noise
      exposure, and then, they were divided into 3 groups based on treatment protocol:
      5 and 6 rats received HBOT at the third hour and 24th hour after the noise,
      respectively, and 6 rats received dexamethasone. Auditory brain stem response
      threshold was measured in all groups before being assigned to the groups, after
      the noise exposure and right before being killed. Cytokine levels at the cochlear
      soft tissues were measured using enzyme-linked immunoassay. RESULTS: Final
      thresholds (10 dB and 5 dB nHL-normal hearing level) of HBOT-24th hour and
      dexamethasone groups were significantly better than that of untreated noise group
      (22.5 dB nHL) (p < 0.05). There was no significant difference between HBOT-24th
      hour group (10 dB nHL) and dexamethasone group (5 dB nHL) (p > 0.05). IL-6 and IL
      1beta of HBOT-third hour group (2.30 ng/mg and 185.43 pg/mg) were significantly
      higher than those of the noise group (0.91 ng/mg and 131.40 pg/mg), dexamethasone
      group (1.19 ng/mg and 112.29 pg/mg) and HBOT-24th hour group (1.34 ng/mg and
      106.69 pg/mg) (p < 0.05). There was no significant difference in IL-6 and IL
      1beta of HBOT-24th hour group, dexamethasone group, noise group, and control
      group (p > 0.05). There was no significant difference in TNF-alpha of the 3
      treatment groups, noise group, and control group (p > 0.05). CONCLUSION: The
      results showed that the most effective method in the treatment of noise-induced
      hearing loss was early initiation of dexamethasone therapy. There could be
      negative effects of HBOT on hearing if it is commenced early after the noise
      (first 3 h). HBOT treatment, which was started at the 24th hour, was found to be
      an effective method.

PMID- 23007645
TI  - Whole genome and transcriptome amplification: practicable tools for sustainable
      tissue biobanking?
AB  - The use of whole genome amplification (WGA) and whole transcriptome amplification
      (WTA) techniques enables the enrichment of DNA and RNA from very small amounts of
      tissue. Here, we tested the suitability of WGA and WTA for tumor tissue
      biobanking. DNA and RNA from 13 standardized and seven non-standardized frozen
      and 12 formalin-fixed, paraffin-embedded (FFPE) clear cell renal cell carcinoma
      specimens (>9 years old) served to test the robustness of the WGA and WTA
      products by reidentifying von Hippel-Lindau (VHL) gene mutations known to exist
      in these samples. The enrichment of DNA and RNA from frozen tissue was up to
      1,291-fold and 423-fold, respectively. The sizes and yields (10- to 73-fold) of
      the amplified DNA obtained from the 12 FFPE samples were generally lower. The
      quality of the RNA from the FFPE samples was too low to reliably perform WTA. Our
      results demonstrate that frozen tumor tissue is very suitable for WGA and WTA.
      All 20 VHL mutations were verified with WGA. Notably, we were able to show that
      18 of the 20 (90 %) VHL mutations are also transcribed. In FFPE tumor tissue, 8
      of 12 cases (67 %) showed the expected mutations after the first WGA. Accurate
      WTA with FFPE material is sophisticated and strongly depends on the modification
      and degradation status of the fixed tissue. We conclude that for sustainable
      tissue biobanking, the use of WGA and WTA is a unique opportunity to provide
      researchers with sufficient amounts of nucleic acids, preferably from limited
      frozen tissue material.

PMID- 23007644
TI  - Brain development during the preschool years.
AB  - The preschool years represent a time of expansive mental growth, with the initial
      expression of many psychological abilities that will continue to be refined into
      young adulthood. Likewise, brain development during this age is characterized by
      its "blossoming" nature, showing some of its most dynamic and elaborative
      anatomical and physiological changes. In this article, we review human brain
      development during the preschool years, sampling scientific evidence from a
      variety of sources. First, we cover neurobiological foundations of early
      postnatal development, explaining some of the primary mechanisms seen at a larger
      scale within neuroimaging studies. Next, we review evidence from both structural
      and functional imaging studies, which now accounts for a large portion of our
      current understanding of typical brain development. Within anatomical imaging, we
      focus on studies of developing brain morphology and tissue properties, including
      diffusivity of white matter fiber tracts. We also present new data on changes
      during the preschool years in cortical area, thickness, and volume. Physiological
      brain development is then reviewed, touching on influential results from several
      different functional imaging and recording modalities in the preschool and early
      school-age years, including positron emission tomography (PET),
      electroencephalography (EEG) and event-related potentials (ERP), functional
      magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and near
      infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of
      the key methodological factors that are required for interpretation. We end with
      a section on multimodal and multidimensional imaging approaches, which we believe
      will be critical for increasing our understanding of brain development and its
      relationship to cognitive and behavioral growth in the preschool years and
      beyond.

PMID- 23007646
TI  - PML promotes MHC class II gene expression by stabilizing the class II
      transactivator.
AB  - Promyelocytic leukemia (PML) nuclear bodies selectively associate with
      transcriptionally active genomic regions, including the gene-rich major
      histocompatibility (MHC) locus. In this paper, we have explored potential links
      between PML and interferon (IFN)-gamma-induced MHC class II expression. IFN-gamma
      induced a substantial increase in the spatial proximity between PML bodies and
      the MHC class II gene cluster in different human cell types. Knockdown
      experiments show that PML is required for efficient IFN-gamma-induced MHC II gene
      transcription through regulation of the class II transactivator (CIITA). PML
      mediates this function through protection of CIITA from proteasomal degradation.
      We also show that PML isoform II specifically forms a stable complex with CIITA
      at PML bodies. These observations establish PML as a coregulator of IFN-gamma
      induced MHC class II expression.

PMID- 23007647
TI  - Structural basis of the junctional anchorage of the cerebral cavernous
      malformations complex.
AB  - The products of genes that cause cerebral cavernous malformations (CCM1/KRIT1,
      CCM2, and CCM3) physically interact. CCM1/KRIT1 links this complex to endothelial
      cell (EC) junctions and maintains junctional integrity in part by inhibiting
      RhoA. Heart of glass (HEG1), a transmembrane protein, associates with KRIT1. In
      this paper, we show that the KRIT1 band 4.1, ezrin, radixin, and moesin (FERM)
      domain bound the HEG1 C terminus (K(d) = 1.2 uM) and solved the structure of this
      assembly. The KRIT1 F1 and F3 subdomain interface formed a hydrophobic groove
      that binds HEG1(Tyr(1,380)-Phe(1,381)), thus defining a new mode of FERM domain
      membrane protein interaction. This structure enabled design of KRIT1(L717,721A),
      which exhibited a >100-fold reduction in HEG1 affinity. Although well folded and
      expressed, KRIT1(L717,721A) failed to target to EC junctions or complement the
      effects of KRIT1 depletion on zebrafish cardiovascular development or Rho kinase
      activation in EC. These data establish that this novel FERM-membrane protein
      interaction anchors CCM1/KRIT1 at EC junctions to support cardiovascular
      development.

PMID- 23007648
TI  - Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome
      segregation.
AB  - The spindle assembly checkpoint (SAC) is essential to ensure proper chromosome
      segregation and thereby maintain genomic stability. The SAC monitors chromosome
      attachment, and any unattached chromosomes generate a "wait anaphase" signal that
      blocks chromosome segregation. The target of the SAC is Cdc20, which activates
      the anaphase-promoting complex/cyclosome (APC/C) that triggers anaphase and
      mitotic exit by ubiquitylating securin and cyclin B1. The inhibitory complex
      formed by the SAC has recently been shown to inhibit Cdc20 by acting as a
      pseudosubstrate inhibitor, but in this paper, we show that Mad2 also inhibits
      Cdc20 by binding directly to a site required to bind the APC/C. Mad2 and the
      APC/C competed for Cdc20 in vitro, and a Cdc20 mutant that does not bind stably
      to Mad2 abrogated the SAC in vivo. Thus, we provide insights into how Cdc20 binds
      the APC/C and uncover a second mechanism by which the SAC inhibits the APC/C.

PMID- 23007649
TI  - The Cbp3-Cbp6 complex coordinates cytochrome b synthesis with bc(1) complex
      assembly in yeast mitochondria.
AB  - Respiratory chain complexes in mitochondria are assembled from subunits derived
      from two genetic systems. For example, the bc(1) complex consists of nine nuclear
      encoded subunits and the mitochondrially encoded subunit cytochrome b. We
      recently showed that the Cbp3-Cbp6 complex has a dual function for biogenesis of
      cytochrome b: it is both required for efficient synthesis of cytochrome b and for
      protection of the newly synthesized protein from proteolysis. Here, we report
      that Cbp3-Cbp6 also coordinates cytochrome b synthesis with bc(1) complex
      assembly. We show that newly synthesized cytochrome b assembled through a series
      of four assembly intermediates. Blocking assembly at early and intermediate steps
      resulted in sequestration of Cbp3-Cbp6 in a cytochrome b-containing complex,
      thereby making Cbp3-Cbp6 unavailable for cytochrome b synthesis and thus reducing
      overall cytochrome b levels. This feedback loop regulates protein synthesis at
      the inner mitochondrial membrane by directly monitoring the efficiency of bc(1)
      complex assembly.

PMID- 23007650
TI  - Group I PAKs function downstream of Rac to promote podosome invasion during
      myoblast fusion in vivo.
AB  - The p21-activated kinases (PAKs) play essential roles in diverse cellular
      processes and are required for cell proliferation, apoptosis, polarity
      establishment, migration, and cell shape changes. Here, we have identified a
      novel function for the group I PAKs in cell-cell fusion. We show that the two
      Drosophila group I PAKs, DPak3 and DPak1, have partially redundant functions in
      myoblast fusion in vivo, with DPak3 playing a major role. DPak3 is enriched at
      the site of fusion colocalizing with the F-actin focus within a podosome-like
      structure (PLS), and promotes actin filament assembly during PLS invasion.
      Although the small GTPase Rac is involved in DPak3 activation and recruitment to
      the PLS, the kinase activity of DPak3 is required for effective PLS invasion. We
      propose a model whereby group I PAKs act downstream of Rac to organize the actin
      filaments within the PLS into a dense focus, which in turn promotes PLS invasion
      and fusion pore initiation during myoblast fusion.

PMID- 23007651
TI  - Biogenesis of the mitochondrial Hsp70 chaperone.
AB  - Chaperones mediate protein folding and prevent deleterious protein aggregation in
      the cell. However, little is known about the biogenesis of chaperones themselves.
      In this study, we report on the biogenesis of the yeast mitochondrial Hsp70
      (mtHsp70) chaperone, which is essential for the functionality of mitochondria. We
      show in vivo and in organello that mtHsp70 rapidly folds after its import into
      mitochondria, with its ATPase domain and peptide-binding domain (PBD) adopting
      their structures independently of each other. Importantly, folding of the ATPase
      domain but not of the PBD was severely affected in the absence of the Hsp70
      escort protein, Hep1. We reconstituted the folding of mtHsp70, demonstrating that
      Hep1 and ATP/ADP were required and sufficient for its de novo folding. Our data
      show that Hep1 bound to a folding intermediate of mtHsp70. Binding of an adenine
      nucleotide triggered release of Hep1 and folding of the intermediate into native
      mtHsp70. Thus, Hep1 acts as a specialized chaperone mediating the de novo folding
      of an Hsp70 chaperone.

PMID- 23007652
TI  - Impact of perioperative hemoglobin levels on postoperative outcomes in gastric
      cancer surgery.
AB  - BACKGROUND: The aim of this study was to evaluate the association of
      postoperative blood transfusion and anemia with postoperative outcomes in gastric
      cancer surgery. METHODS: We enrolled 588 patients who had undergone curative
      resection for gastric cancer. Input variables for risk assessment consisted of 3
      categories: patient demographics, surgical and pathological factors, and anemia
      related factors. Postoperative outcomes included 30-day morbidity and mortality.
      Univariate and multivariate analyses were performed to identify risk factors
      influencing postoperative complications. RESULTS: The rate of total complications
      was 19.0%. Comorbidity, lowest hemoglobin (Hb) level from the operative day up to
      postoperative day 7 (LOW-Hb), the percentage of drop in Hb level on postoperative
      day 2 (POD2-Hb change), and postoperative transfusion were independent risk
      factors in the multivariate analysis, with LOW-Hb and postoperative transfusion
      found to be the most significant factors. When LOW-Hb was >=9.0 g/dL,
      postoperative complications were higher in the transfused group than in the non
      transfused group (60.0 vs. 14.2%, respectively, p = 0.024), but when LOW-Hb was
      <9.0 g/dL, postoperative complications were not different between the 2 groups
      (44.6 vs. 37.5%, p = 0.525). CONCLUSION: The lowest postoperative Hb level and
      postoperative transfusion were the most significant risk factors for
      postoperative complications in gastric cancer surgery.

PMID- 23007653
TI  - Assessment of a real-time ultrasound-guided spinal technique using SonixGPSTM in
      human cadavers.

PMID- 23007654
TI  - Is schizoaffective disorder still a neglected condition in the scientific
      literature?

PMID- 23007655
TI  - Measurement of the elution strength and peak shape enhancement at increasing
      modifier concentration and temperature in RPLC.
AB  - Two approaches are proposed to measure the effect of different experimental
      factors (such as the modifier concentration and temperature) on the elution
      strength and peak shape in reversed-phase liquid chromatography, which quantify
      the percentage change in the retention factor and peak width (referred to the
      weakest conditions) per unit change in the experimental factor. The approaches
      were applied to the separation of a set of flavonoids with aqueous micellar
      mobile phases of the surfactant Brij-35 (polyoxyethylene(23)dodecanol), in
      comparison with acetonitrile-water mixtures, using an Eclipse XDB-C18 column. The
      particular interaction of each flavonoid with the oxyethylene chains of Brij-35
      molecules (adsorbed on the stationary phase or forming micelles) changed the
      elution window, distribution of chromatographic peaks and partitioning kinetics,
      depending on the hydroxyl substitution in the aromatic rings of flavonoids. At 25
      degrees C, peak shape with Brij-35 mobile phases was significantly poorer with
      regard to acetonitrile-water mixtures. At increasing temperature, the efficiency
      of Brij-35 increased, approaching at 80  degrees C the values obtained at
      equilibrium conditions, already reached with acetonitrile at 25  degrees C.

PMID- 23007656
TI  - Fast screening of 88 pharmaceutical drugs and metabolites in whole blood by
      ultrahigh-performance liquid chromatography-tandem mass spectrometry.
AB  - Forensic investigations involving acute or lethal intoxication, drug-facilitated
      sexual assault, driving or workplace impairment frequently require the analysis
      of fresh or postmortem blood samples to check out a wide variety of
      pharmaceutical and illicit drugs, even after single-dose consumption. A sensitive
      and selective ultrahigh-performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) screening method was developed for fast screening of
      88 psychoactive drugs and metabolites in blood samples, including the ones most
      frequently involved in acute intoxications and forensic investigations in Italy.
      The new method allows short sample processing and analysis time (the whole
      procedure can be accomplished in less than 30 min) together with the simultaneous
      monitoring of a large number of pharmaceutical substances. These features
      represent crucial factors in the approach of acute intoxications, when the
      patient requires urgent and appropriate therapy. Blood sample treatment was
      limited to protein precipitation. Two UHPLC-MS/MS runs in positive and negative
      electrospray ionization modes were performed. The data were acquired at unit mass
      resolution in the selected reaction monitoring mode. According to international
      guidelines, linearity range, precision, trueness, detection and quantification
      limits, recovery, selectivity, specificity, carryover, and matrix effect
      phenomena were determined. Despite the limited sample purification and the
      inherent decreased chance of eliminating any potential interference, the present
      multiresidue screening method proved extremely effective and sensitive, allowing
      the detection of all tested drugs, even those belonging to structurally different
      classes of substances. Moreover, the developed method is easily susceptible to
      further expansion to encompass more drugs, either new or those becoming important
      for criminal investigation. This protocol was also applied to the analysis of
      authentic blood samples collected from victims of various crimes in routine
      casework, whose relevance in forensic investigations is presented in five cases.

PMID- 23007657
TI  - Elemental speciation.

PMID- 23007658
TI  - Studying proteolysis of cyclin B at the single cell level in whole cell
      populations.
AB  - Equal distribution of chromosomes between the two daughter cells during cell
      division is a prerequisite for guaranteeing genetic stability. Inaccuracies
      during chromosome separation are a hallmark of malignancy and associated with
      progressive disease. The spindle assembly checkpoint (SAC) is a mitotic
      surveillance mechanism that holds back cells at metaphase until every single
      chromosome has established a stable bipolar attachment to the mitotic spindle.
      The SAC exerts its function by interference with the activating APC/C subunit
      Cdc20 to block proteolysis of securin and cyclin B and thus chromosome separation
      and mitotic exit. Improper attachment of chromosomes prevents silencing of SAC
      signaling and causes continued inhibition of APC/C(Cdc20) until the problem is
      solved to avoid chromosome missegregation, aneuploidy and malignant growths. Most
      studies that addressed the influence of improper chromosomal attachment on APC/C
      dependent proteolysis took advantage of spindle disruption using depolymerizing
      or microtubule-stabilizing drugs to interfere with chromosomal attachment to
      microtubules. Since interference with microtubule kinetics can affect the
      transport and localization of critical regulators, these procedures bear a risk
      of inducing artificial effects. To study how the SAC interferes with APC/C
      dependent proteolysis of cyclin B during mitosis in unperturbed cell populations,
      we established a histone H2-GFP-based system which allowed the simultaneous
      monitoring of metaphase alignment of mitotic chromosomes and proteolysis of
      cyclin B. To depict proteolytic profiles, we generated a chimeric cyclin B
      reporter molecule with a C-terminal SNAP moiety (Figure 1). In a self-labeling
      reaction, the SNAP-moiety is able to form covalent bonds with alkylguanine
      carriers (SNAP substrate) (Figure 1). SNAP substrate molecules are readily
      available and carry a broad spectrum of different fluorochromes. Chimeric cyclin
      B-SNAP molecules become labeled upon addition of the membrane-permeable SNAP
      substrate to the growth medium (Figure 1). Following the labeling reaction, the
      cyclin B-SNAP fluorescence intensity drops in a pulse-chase reaction-like manner
      and fluorescence intensities reflect levels of cyclin B degradation (Figure 1).
      Our system facilitates the monitoring of mitotic APC/C-dependent proteolysis in
      large numbers of cells (or several cell populations) in parallel. Thereby, the
      system may be a valuable tool to identify agents/small molecules that are able to
      interfere with proteolytic activity at the metaphase to anaphase transition.
      Moreover, as synthesis of cyclin B during mitosis has recently been suggested as
      an important mechanism in fostering a mitotic block in mice and humans by keeping
      cyclin B expression levels stable, this system enabled us to analyze cyclin B
      proteolysis as one element of a balanced equilibrium.

PMID- 23007659
TI  - miR-183 as a molecular and protective biomarker for cancer in schizophrenic
      subjects.
AB  - Previous studies have suggested that schizophrenia is associ-ated with a reduced
      risk of cancer. Genes that are involved in cell cycle regulation seem to have
      additional functions in post-mitotic neurons involved in neuronal migration and
      synaptic plasticity. MicroRNAs (miRNAs) play a dominant role in the regulation of
      gene expression in the central nervous system (CNS). Due to their involvement in
      a large number of CNS pathways, miRNAs pose as appealing molecules for further
      investigation, with potential diagnostic, prognostic and therapeutic value. In
      the present study, we investigated the potential association between cancer and
      schizophrenia in 2 patient sample groups. We analyzed a large number of miRNAs in
      a control group of 6 schizophrenic patients and a study group of 8 schizophrenic
      patients with a solid tumor. A comparison between the control and study groups
      showed that only miR-183 was differentially expressed. Specifically, a
      significant downregulation of miR-183 in the samples of the study group was
      observed. Although a larger sample size is required to validate this result for
      the general patient population, our findings provide a first indication that miR
      183 may play a role in regulating the expression of other genes with onco
      suppressor activity. Our results are in agreement with the theory that patients
      with schizophrenia may have a tumor suppressor gene or enhanced neuronal
      apoptotic activities. Further studies are required in order to shed light on the
      role of miRNAs and particularly, on the suppressive role of miR-183 in the
      neurobiological pathways involved in schizophrenia.

PMID- 23007660
TI  - Short-term outcomes of laparoscopic gastric plication in morbidly obese patients:
      importance of postoperative follow-up.
AB  - Demand for feasible, safe, and preferably low-cost methods of weight reduction is
      rising every day. The present study reports findings from laparoscopic gastric
      plication (LGP), which is a new restrictive bariatric technique, combined with a
      postoperative follow-up program. A 2-year prospective study was performed
      following LGP in 53 female morbidly obese patients from Gorgan, Iran, with a mean
      age of 36.3 years and mean body mass index (BMI) of 42.6 kg/m(2) (35.3-62.4).
      Through a four-port approach, the greater omentum and short gastric vessels were
      transected and the greater curvature was imbricated into the body of the stomach
      with two rows of nonabsorbable sutures. After surgery, all patients were
      scheduled to attend a weekly group meeting for behavioral modification and
      psychotherapy. The mean operative time and hospital stay was 95 min and 72 h,
      respectively. No intraoperative complications occurred. Mean percentages of
      excess weight loss (%EWL) were 25.6 %, 54.2 %, 70.2 %, and 74.4 % after 1, 6, 12,
      and 24 months, respectively. Six patients lost >84 % of their excess weight after
      24 months. Patients who did not participate in the group meetings had a lower
      %EWL after 12 (79.5 % vs. 55.6 %) and 24 months (90 % vs. 43.4 %) compared with
      the patients who regularly participated in the group meetings (P < 0.005). LGP is
      a feasible, safe, and effective surgical method for weight loss for at least 24
      months when performed on morbidly obese patients. Postoperative group meetings
      (POGM) for psychotherapy and behavioral modification helped patients to achieve
      better results.

PMID- 23007662
TI  - Histopathological characteristics of the "spot sign" in spontaneous intracerebral
      hemorrhage.

PMID- 23007661
TI  - Insights into the uranium(VI) speciation with Pseudomonas fluorescens on a
      molecular level.
AB  - Microorganisms have great potential to bind and thus transport actinides in the
      environment. Thus microbes indigenous to designated nuclear waste disposal sites
      have to be investigated regarding their interaction mechanisms with soluble
      actinyl ions when assessing the safety of a planned repository. This paper
      presents results on the pH-dependent sorption of U(VI) onto Pseudomonas
      fluorescens isolated from the granitic rock aquifers at Aspo Hard Rock
      Laboratory, Sweden. To characterize the U(VI) interaction on a molecular level,
      potentiometric titration in combination with time-resolved laser-induced
      fluorescence spectroscopy (TRLFS) were applied. This paper as a result is one of
      the very few sources which provide stability constants of U(VI) complexed by cell
      surface functional groups. In addition the bacteria-mediated liberation of
      inorganic phosphate in dependence on [U(VI)] at different pHs was studied to
      judge the influence of phosphate release on U(VI) mobilization. The results
      demonstrate that in the acidic pH range U(VI) is bound by the cells mainly via
      protonated phosphoryl and carboxylic sites. The complexation by carboxylic groups
      can be observed over a wide pH range up to around pH 7. At neutral pH fully
      deprotonated phosphoryl groups are mainly responsible for U(VI) binding. U(VI)
      can be bound by P. fluorescens with relatively high thermodynamic stability.

PMID- 23007663
TI  - Self-ordering of metallogrid complexes via directed hydrogen-bonding.
AB  - Reaction of imidazole aldehydes with dihydrazino derivatives of 2
      phenylpyrimidine provides a family of bis(acylhydrazone) ligands which form [2 *
      2] metallogrid complexes with transition metal ions including Fe(II), Co(II),
      Cu(II) and Zn(II). The free ligands show H-bonding interactions, both donor and
      acceptor, largely involving the imidazole units, while binding of the metal ions
      occupies all the acceptor sites and leaves only the pyrrolic-NH site as an H-bond
      donor, although its deprotonation by a strong base can regenerate an acceptor.
      These H-bonding interactions have been studied by (1)H NMR spectroscopy in
      solution and in the solid state by means of several crystal structure
      determinations. The Fe(II) grids appear to be exclusively high-spin species over
      a wide temperature range in solution. In the solid state various forms of spin
      crossover behaviour can be observed between 1.8 and 300 K, which has been
      rationalised in terms of the varied forms of hydrogen-bonding possible in the
      crystalline state.

PMID- 23007664
TI  - Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate delivery
      of a novel aspirin, curcumin and sulforaphane drug combination regimen.
AB  - Pancreatic cancer is the fourth largest cause of cancer deaths in the Unites
      States and the prognosis is grim with <5% survival chances upon diagnosis. The
      objective of this study was to assess the combined chemopreventive effect of
      solid lipid nanoparticle (SLN) encapsulated drugs aspirin (ASP), curcumin (CUR)
      and free sulforaphane (SFN) for the chemoprevention of pancreatic cancer.
      Experiments were carried out (1) to evaluate the feasibility of encapsulation of
      these chemopreventive agents within solid lipid systems and (2) to measure the
      synergistic effects of a combination of ASP with CUR in SLNs mixed with free SFN
      against cell proliferation and apoptosis in pancreatic cancer cells, MIA PaCa-2
      and Panc-1. The SLNs were prepared using a modified solvent evaporation technique
      and were characterized for particle sizing, encapsulation efficiency and drug
      release. ASP and CUR SLNs were formulated within the particle size range of 150
      250 nm and were found to have an encapsulation efficiency of 85 and 69%,
      respectively. Sustained release of drugs over a 96 h period from SLNs was
      observed. The SLNs were stable over a 3-month storage period at room temperature.
      Cell viability studies demonstrated that combinations of low doses of ASP SLN (25
      uM), CUR SLN (2.5 uM) and free SFN (5 uM) significantly reduced cell viability by
      43.6 and 48.49% in MIAPaca-2 and Panc-1 cell lines, respectively. Furthermore,
      increased apoptosis of 61.3 and 60.37% was found in MIA Paca-2 and Panc-1 cell
      lines, respectively, in comparison to the individual doses administered.
      Synergistic effects were demonstrated using MTS and apoptosis assays. Thus, this
      study successfully demonstrated the feasibility of using a solid lipid
      nanoparticulate system for the first time to deliver this novel combination
      chemoprevention regimen, providing valuable evidence for the usability of
      nanotechnology-based drug regimens towards pancreatic cancer chemoprevention.

PMID- 23007665
TI  - Use of partial AUC (PAUC) to evaluate bioequivalence--a case study with complex
      absorption: methylphenidate.
AB  - PURPOSE: Methylphenidate modified-release products produce early and late peak
      concentrations critical for treatment of morning and afternoon symptoms of
      attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE)
      criteria cannot be applied to these products. The performance of partial area
      under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were
      independently evaluated for two products. METHODS: A two-stage analysis was
      performed on plasma data for two methylphenidate modified-release products
      (Product 1 and 2). Simulations using the fitted parameters determined how changes
      in fast absorption rate constant (K0Fast) and fraction available (F1) affected
      curve shape and BE determination using Cmax, AUCINF and PAUC. RESULTS: The
      sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in
      K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference)
      ratios for PAUC0-4h are more responsive to both decreases and increases in
      K0Fast(test) than Product 2. Product 2 showed a greater response in the mean
      PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased
      and less response as the value is increased. CONCLUSIONS: PAUC estimated curve
      shape is sensitive to changes in absorption and are product specific, and may
      require a new PAUC metric for each drug. A non-product specific metric to assess
      curve shape is warranted.

PMID- 23007666
TI  - Strong metal-metal coupling in mixed-valent intermediates [Cl(L)Ru(MU
      tppz)Ru(L)Cl]+, L = beta-diketonato ligands, tppz = 2,3,5,6-tetrakis(2
      pyridyl)pyrazine.
AB  - Five diruthenium(II) complexes [Cl(L)Ru(MU-tppz)Ru(L)Cl] (1-5) containing
      differently substituted beta-diketonato derivatives (1: L = 2,4-pentanedionato;
      2: L = 3,5-heptanedionato; 3: L = 2,2,6,6-tetramethyl-3,5-heptanedionato; 4: L =
      3-methyl-2,4-pentanedionato; 5: L = 3-ethyl-2,4-pentanedionato) as ancillary
      ligands (L) were synthesized and studied by spectroelectrochemistry (UV-Vis-NIR,
      electron paramagnetic resonance (EPR)). X-ray structural characterisation
      revealed anti (1, 2, 5) or syn (3) configuration as well as non-planarity of the
      bis-tridentate tppz bridge and strong dpi(Ru(II)) -> pi*(pyrazine, tppz) back
      bonding. The widely separated one-electron oxidation steps,
      Ru(II)Ru(II)/Ru(II)Ru(III) and Ru(II)Ru(III)/Ru(III)Ru(III), result in large
      comproportionation constants (K(c)) of >=10(10) for the mixed-valent
      intermediates. The syn-configurated (n) exhibits a particularly high K(c) of
      10(12) for n = 1+, accompanied by density functional theory (DFT)-calculated
      minimum Ru-N bond lengths for this Ru(II)Ru(III) intermediate. The
      electrogenerated mixed-valent states 1(+)-5(+) exhibit anisotropic EPR spectra at
      110 K with average values <g> of 2.304-2.234 and g anisotropies Deltag = g(1)
      g(3) of 0.82-0.99. Metal-to-metal charge transfer (MMCT) absorptions occur for
      1(+)-5(+) in the NIR region at 1660 nm-1750 nm (epsilon ~ 2700 dm(3) mol(-1) cm(
      1), Deltanu(1/2) ~ 1800 cm(-1)). DFT calculations of 1(+) and 3(+) yield
      comparable Mulliken spin densities of about 0.60 for the metal ions,
      corresponding to valence-delocalised situations (Ru(2.5))(2). Rather large spin
      densities of about -0.4 were calculated for the tppz bridges in 1(+) and 3(+).
      The calculated electronic interaction values (V(AB)) for 1(+)-5(+) are about 3000
      cm(-1), comparable to that for the Creutz-Taube ion at 3185 cm(-1). The DFT
      calculations predict that the Ru(III)Ru(III) forms in 1(2+)-5(2+) prefer a
      triplet (S = 1) ground state with DeltaE (S = 0 - S = 1) ~5000 cm(-1). One
      electron reduction takes place at the tppz bridge which results in species
      [Cl(L)Ru(II)(MU-tppz(-))Ru(II)(L)Cl](-) (1(-)-3(-), 5(-)) which exhibit free
      radical-type EPR signals and NIR transitions typical of the tppz radical anion.
      The system 4(n) is distinguished by lability of the Ru-Cl bonds.

PMID- 23007667
TI  - Is ICGA still relevant in inflammatory eye disorders? Why this question has to be
      dealt with separately from other eye conditions.

PMID- 23007668
TI  - Surgical management of retinal detachment because of macular hole in highly
      myopic eyes.
AB  - PURPOSE: The purpose of this study was to review the current management of
      macular hole retinal detachment in highly myopic eyes. METHODS: We searched
      English MEDLINE databases from January 1997 to January 2011 for surgical
      management of macular hole retinal detachment in highly myopic eyes. The main
      outcomes reported include retinal reattachment and visual acuity after primary
      surgery. RESULTS: Surgical procedures including pneumoretinopexy, pars plana
      vitrectomy with gas or silicone oil tamponade with or without laser therapy
      around the macular hole, and macular buckling have been the primary treatment
      choices. New techniques, including internal limiting membrane or epiretinal
      membrane peeling and heavy silicone oil tamponade, have been introduced over the
      last decade, and use of optical coherence tomography has allowed evaluation of
      the postoperative anatomical status of holes undetectable by conventional
      ophthalmoscope or lens biomicroscope. Poor functional and anatomical outcomes and
      nonclosure or reopening of a macular hole are still crucial problems, and some
      patients may require multiple procedures. CONCLUSION: Macular hole retinal
      detachment in highly myopic eyes is one of the most difficult types of retinal
      detachment to treat, and its primary treatment choice is still controversial,
      although the different surgical techniques reported in this review have been
      demonstrated as good surgical options. Randomized clinical trials are largely
      lacking.

PMID- 23007669
TI  - "Dissociated optic nerve fiber layer appearance" after internal limiting membrane
      removal is inner retinal dimpling.
AB  - PURPOSE: To examine volume-rendered spectral-domain optical coherence tomography
      images in patients who had undergone vitrectomy, many of whom had internal
      limiting membrane removal to investigate a condition termed "dissociated optic
      nerve fiber layer appearance." METHODS: Patients who had undergone vitrectomy for
      either macular hole or epiretinal membrane were evaluated. Spectral-domain
      optical coherence tomography B-scan images were acquired with the use of eye
      tracking at an interval of either 30 MUm or 60 MUm. These were registered and
      exported to a volume-rendering program, and the resultant volume-rendered images
      were evaluated. The images were graded for the presence of inner retinal
      abnormalities, and correlates were made to corresponding alterations seen in
      fundus photographs and B-scan spectral-domain optical coherence tomography
      images. RESULTS: There were 25 eyes of 24 patients with a mean age of 72.4 (+/-
      7.3) years, 15 of whom were women. The primary preoperative diagnosis was macular
      hole in 10 eyes (40%) and epiretinal membrane in 15 eyes (60%). As part of the
      surgery, 18 eyes (72%) had planned peeling of the internal limiting membrane.
      Volume rendering showed that 13 eyes had pitting or dimples of the inner retinal
      surface that seemed to follow the course of the nerve fiber layer in the region
      of the macula. The inner retinal dimples occurred only in eyes that had internal
      limiting membrane peeling. Correlation of the volume-rendered images with B-scan
      spectral-domain optical coherence tomography showed focal areas of thinning of
      the ganglion cell layer with decreased reflectivity from the nerve fiber layer in
      the areas of the dimples. CONCLUSION: A high proportion of eyes with internal
      limiting membrane peeling develop inner retinal dimples that course along the
      path of the nerve fiber layer. The dimples seem to be the result of an interplay
      between trauma and healing processes constrained by nerve fiber layer and do not
      appear to be because of dissociation of optic nerve fibers. The true nature of
      the abnormalities induced should be investigated to evaluate the long-term risks
      and benefits of routine internal limiting membrane peeling.

PMID- 23007670
TI  - Vitrectomy under air.

PMID- 23007671
TI  - Diagnostic and therapeutic challenges.

PMID- 23007672
TI  - Crystalline retinopathy from primary hyperoxaluria.

PMID- 23007673
TI  - Re: Choroid is thinner in inferior region of optic disks of normal eyes.

PMID- 23007675
TI  - Re: Sutureless 23-gauge versus 20-gauge vitrectomy with silicone oil injection in
      rhegmatogenous retinal detachment.

PMID- 23007677
TI  - Fluorinated beta-nitro amines by a selective ZrCl4-catalyzed aza-Henry reaction
      of (E)-trifluoromethyl aldimines.
AB  - ZrCl(4) was found to be an ideal catalyst to promote aza-Henry reactions between
      trifluoromethyl aldimines and some nitro alkanes giving new fluorinated beta
      nitro amines. The reaction is strongly influenced by the CF(3) group, the yield
      by the alkyl chain of the nitro compound, while the stereochemical outcome seems
      to be unaffected, the anti isomer being always the major product.

PMID- 23007679
TI  - [Evaluation of current assessment tools in early detection of developmental
      deviations in speech and language in the German preventive paediatric examination
      (Kindervorsorgeuntersuchung U8)].
AB  - OBJECTIVE: The current analysis is a contribution to application information and
      quality assurance. It is intended to evaluate and optimise the use of German
      developmental screening instruments to identify deficits in speech, speech
      fluency and language during the early paediatric toddler check-up
      Kindervorsorgeuntersuchung U8 in the age of 43-50 months. METHODS: A systematic
      literature search was conducted seeking current specific, standardised, norm
      referenced assessment tools, particularly those relevant to the early detection
      of developmental speech and language retardation. They were subsequently
      evaluated quantitatively and qualitatively with specific regard to 15
      psychometric criteria and construction features. RESULTS: 4 assessment tools (ETS
      4-8; KiSS; SSV; TSVK-Screen) resulted from literature search. They were subjected
      to a detailed and rigorous comparative analysis. Quantitatively they met 7-12 of
      the 15 psychometric criteria whose quality was partly low or demonstrated survey
      standard to a lesser degree. CONCLUSION: These developmental screening
      instruments utilised in the paediatric toddler check-up U8 cannot be recommended
      without reservation with regard to a dichotomous decision (suspected disorder
      versus no suspected disorder). More qualificatory research focusing specifically
      on the existing screenings and the construction of new screening tools is
      required in order to gain vital developmental psychological information of the
      speech/language status of a child during the preventive paediatric examination
      U8. Alternatively, it should be evaded to the approach of taking diagnostic
      language developmental tests.

PMID- 23007678
TI  - Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance
      in diabetic mice.
AB  - Diabetic patients are more susceptible to the development of chronic wounds than
      non-diabetics. The impaired healing properties of these wounds, which often
      develop debilitating bacterial infections, significantly increase the rate of
      lower extremity amputation in diabetic patients. We hypothesize that bacterial
      biofilms, or sessile communities of bacteria that reside in a complex matrix of
      exopolymeric material, contribute to the severity of diabetic wounds. To test
      this hypothesis, we developed an in vivo chronic wound, diabetic mouse model to
      determine the ability of the opportunistic pathogen, Pseudomonas aeruginosa, to
      cause biofilm-associated infections. Utilizing this model, we observed that
      diabetic mice with P. aeruginosa-infected chronic wounds displayed impaired
      bacterial clearing and wound closure in comparison with their non-diabetic
      littermates. While treating diabetic mice with insulin improved their overall
      health, it did not restore their ability to resolve P. aeruginosa wound
      infections or speed healing. In fact, the prevalence of biofilms and the
      tolerance of P. aeruginosa to gentamicin treatment increased when diabetic mice
      were treated with insulin. Insulin treatment was observed to directly affect the
      ability of P. aeruginosa to form biofilms in vitro. These data demonstrate that
      the chronically wounded diabetic mouse appears to be a useful model to study
      wound healing and biofilm infection dynamics, and suggest that the diabetic wound
      environment may promote the formation of biofilms. Further, this model provides
      for the elucidation of mechanistic factors, such as the ability of insulin to
      influence antimicrobial effectiveness, which may be relevant to the formation of
      biofilms in diabetic wounds.

PMID- 23007680
TI  - [Oral health of pregnant women and their awareness of oral hygiene].
AB  - AIM: Pregnancy is related with changes in oral health. While the medical care of
      pregnant women in Germany is well-regulated, there are no structured
      recommendations for dental examinations. During an "Oral Health Awareness Week"
      the periodontal conditions of pregnant women in the Federal State of Thuringia
      (Germany) were examined. METHODS: 85 pregnant women participated in this study.
      Oral health indices (PSI, BoP and DMFT) were recorded. 61 of the 85 women
      followed the invitation to repeat the investigations after parturition.
      Additionally, birth weight and height of the newborn were recorded. RESULTS:
      There were no correlations between periodontal condition and birth weight.
      However, pregnant women demonstrated in high levels periodontal inflammation
      (only 1.2% showed periodontal health). Pregnant woman with periodontitis (PSI 3
      and 4) demonstrated clear deficiencies in health education regarding oral health
      and adverse pregnancy outcomes. CONCLUSIONS: These findings implicate the
      importance of periodontal care in pregnant women. An association between
      periodontitis and reduced birth weight was not observed in the studied Thuringian
      cohort.

PMID- 23007681
TI  - Pharmacokinetic and safety evaluation of the use of ciprofloxacin on an isoniazid
      rifampicin regimen in rabbits.
AB  - The combination of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) is
      used in the treatment of tuberculosis. Although this treatment is effective in
      most clinical cases, the side-effects and the development of mycobacterium
      resistance have hindered its success. There is evidence that the combination of
      INH, RMP and ciprofloxacin (CIPRO) is useful in the treatment of tuberculosis.
      However, the influence of this drug combination on the hepatotoxicity of INH is
      unknown. In this study, the safety of combined INH, RMP and CIPRO was evaluated.
      Male albino rabbits (n = 20) were divided into four groups and subjected to
      multiple oral doses for 7 days according to the following treatments: water
      (group 1); 50 mg/kg INH (group 2); 50 mg/kg INH + 100 mg/kg RMP (group 3) and 50
      mg/kg INH + 100 mg/kg RMP + 50 mg/kg CIPRO (group 4). Blood samples were taken
      before and after treatments for the determination of ALT, AST, ALP and bilirubin
      to assess hepatotoxicity. For pharmacokinetic analysis, serial blood samples were
      collected over 24 h on day 7 of treatment. Plasma concentrations of INH and
      acetylisoniazid (AcINH) were determined by HPLC. Biochemical parameters did not
      show any statistically significant differences between the groups that received
      the drug combinations. The pharmacokinetic profile of INH was also similar for
      both groups of combinations. These findings allow us to infer that the inclusion
      of CIPRO did not increase the risk of hepatotoxicity when compared with the
      classic combination of INH and RMP.

PMID- 23007682
TI  - Characterization of a variety of neutralizing anti-heparin-binding epidermal
      growth factor-like growth factor monoclonal antibodies by different immunization
      methods.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member
      of the epidermal growth factor family. The accumulated evidence on the tumor
      progressing roles of HB-EGF has suggested that HB-EGF-targeted cancer therapy is
      expected to be promising. However, the generation of neutralizing anti-HB-EGF
      monoclonal antibodies (mAbs) has proved difficult. To overcome this difficulty,
      we performed a hybridoma approach using mice from different genetic backgrounds,
      as well as different types of HB-EGF immunogens. To increase the number of
      hybridoma clones to screen, we used an electrofusion system to generate
      hybridomas and a fluorometric microvolume assay technology to screen anti-HB-EGF
      mAbs. We succeeded in obtaining neutralizing anti-HB-EGF mAbs, primarily from
      BALB/c and CD1 mice, and these were classified into 7 epitope bins based on their
      competitive binding to the soluble form of HB-EGF (sHB-EGF). The mAbs showed
      several epitope bin-dependent characteristics, including neutralizing and binding
      activity to human sHB-EGF, cross-reactivity to mouse/rat sHB-EGF and binding
      activity to the precursor form of HB-EGF. The neutralizing activity was also
      validated in colony formation assays. Interestingly, we found that the
      populations of mAb bins and the production rates of the neutralizing mAbs were
      strikingly different by mouse strain and by immunogen type. We succeeded in
      generating a variety of neutralizing anti-HB-EGF mAbs, including potent sHB-EGF
      neutralizers that may have potential as therapeutic agents for treating HB-EGF
      dependent cancers. Our results also suggest that immunization approaches using
      different mouse strains and immunogen types affect the biological activity of
      individual neutralizing antibodies.

PMID- 23007683
TI  - An integrated cytogenetic and physical map reveals unevenly distributed
      recombination spots along the papaya sex chromosomes.
AB  - Papaya is a model system for the study of sex chromosome evolution in plants.
      However, the cytological structures of the papaya chromosomes remain largely
      unknown and chromosomal features have not been linked with any genetic or genomic
      data. We constructed a cytogenetic map of the papaya sex chromosome (chromosome
      1) by hybridizing 16 microsatellite markers and 2 cytological feature-associated
      markers on pachytene chromosomes using fluorescence in situ hybridization (FISH).
      Except for three markers, the order of the markers was concordant to that of
      marker loci along the linkage map. This discrepancy was likely caused by skewed
      segregation in the highly heterochromatic or centromeric regions. The papaya sex
      chromosome is largely euchromatic, its heterochromatin spans about 15 % of the Y
      chromosome and is mostly restricted to the centromeric and pericentromeric
      regions. Analysis of the recombination frequency along the papaya sex chromosome
      revealed a complete suppression of recombination in the centromere and
      pericentromere region and 60 % higher recombination rate in the long arm than in
      the short arm. The uneven distribution of recombination events might be caused by
      differences in sequence composition. Sequence analysis of 18 scaffolds in total
      length of 15 Mb revealed higher gene density towards the telomeres and lower gene
      density towards the centromere, and a relatively higher gene density in the long
      arm than in the short arm. In an opposite trend, the centromeric and
      pericentromeric region contained the highest repetitive sequences and the long
      arm showed the lowest repetitive sequences. This cytogenetic map provides
      essential information for evolutionary study of sex chromosomes in Caricaceae and
      will facilitate the analysis of papaya sex chromosomes.

PMID- 23007684
TI  - Intractable ascites as a manifestation of Wolman's disease: report of two sibs.
AB  - Wolman disease (WD) is a rare, inherited, rapidly fatal condition presenting in
      early infancy. The disease manifests in the first month of life with failure to
      thrive, vomiting, diarrhea, abdominal distension, hepatosplenomegaly and
      bilateral adrenal calcification and is nearly always fatal before the age of 1
      year. Barring a case report of isolated fetal ascites, there is no report of
      intractable ascites as the presentation of WD till date. We report two siblings
      with WD who both had intractable ascites and required therapeutic paracentesis,
      albumin infusion, and diuretics to control tense ascites. Although rare, WD
      should be considered in the differential diagnosis of infantile ascites.

PMID- 23007685
TI  - Quantification and analysis of ecdysis in the hornworm, Manduca sexta, using
      machine vision-based tracking.
AB  - We have developed a machine vision-based method for automatically tracking
      deformations in the body wall to monitor ecdysis behaviors in the hornworm,
      Manduca sexta. The method utilizes naturally occurring features on the animal's
      body (spiracles) and is highly accurate (>95 % success in tracking). Moreover, it
      is robust to unanticipated changes in the animal's position and in lighting, and
      in the event tracking of specific features is lost, tracking can be reestablished
      within a few cycles without input from the user. We have paired our tracking
      technique with electromyography and have also compared our in vivo results to
      fictive motor patterns recorded from isolated nerve cords. We found no major
      difference in the cycle periods of contractions during naturally occurring
      ecdysis compared to ecdysis initiated prematurely through injection of the
      peptide ecdysis-triggering hormone, and we confirmed that the ecdysis period in
      vivo is statistically similar to that of the fictive motor pattern.

PMID- 23007686
TI  - Mutual interactions between depression/quality of life and adherence to a
      multidisciplinary lifestyle intervention in obesity.
AB  - CONTEXT: There is scarce knowledge of the interaction between depression/health
      related quality of life (HRQOL) and lifestyle intervention in obesity. OBJECTIVE:
      The aim of the study was to establish whether baseline mood status or HRQOL
      affects attendance to educational or exercise sessions and whether attendance to
      these two components of the intervention affects mood and/or HRQOL in obesity.
      DESIGN: A total of 282 overweight/obese subjects (body mass index, 33.4 +/- 5.9
      kg/m(2); 103 males, 179 females; age, 53.8 +/- 13.0 yr, mean +/- sd) were
      consecutively enrolled in a multidisciplinary lifestyle intervention program.
      During the intensive phase of the intervention (3 months) patients were invited
      to attend eight educational sessions and 26 exercise group sessions. RESULTS:
      Poor adherence to exercise sessions is predicted by baseline depressive mood (P
      =0.006) and by low levels of HRQOL (domains of Vitality, Physical Role
      Functioning, Social Functioning, Mental Composite, Physical Composite Scores) (P
      < 0.05). Attendance to the educational sessions is associated with beneficial
      effects of the lifestyle intervention on depressive symptoms (P < 0.013) and on
      several mental domains of HRQOL (P < 0.041); attendance to the exercise sessions
      predicted the beneficial effects on perceived general health (P < 0.021) and body
      mass index (P < 0.011). Attendance to both educational and exercise components is
      associated (P < 0.05) with the reductions in waist circumference, fat mass, and
      blood pressure observed after the intensive phase of the intervention.
      CONCLUSIONS: Measurement of depressive mood and HRQOL before lifestyle
      intervention allows identification of patients at increased risk of attrition
      with exercise and educational sessions. Both the exercise and the educational
      sessions are essential for gaining the full spectrum of psychological and
      clinical benefits from multidisciplinary lifestyle intervention in obesity.

PMID- 23007687
TI  - Evaluation of quinoline as a remote sensitiser for red and near-infrared emissive
      lanthanide(III) ions in solution and the solid state.
AB  - In order to evaluate quinoline as a remote sensitiser, we have prepared a DTPA
      based ligand, H3L, bearing quinoline bisamide arms for the complexation of a
      range of lanthanide(III) ions to give the neutral complexes LnLwhere Ln(3+) =
      Y(3+), Eu(3+), Sm(3+), Tb(3+), Er(3+), Yb(3+), Nd(3+), Gd(3+). Detection of the
      phosphorescence signal exhibited by the GdLcomplex at 77 K confirmed that the
      triplet energy level of the sensitiser at 21,190 cm(-1) was suitable for the
      indirect population of a range of lanthanide luminescent states. A full
      photophysical analysis of the complexes reveals that SmL and EuL display red
      emission when excited through the ligand-based absorption band centred at 330 nm,
      extending the excitation to violet light around 370 nm. We demonstrate that
      quinoline sensitizes near-infrared emission in the YbL, ErL and NdL complexes, in
      powder form as well as in solution. Most importantly, the luminescence for YbL
      and NdL was sufficiently efficient to be detected in non-deuterated solvent.

PMID- 23007688
TI  - The specificity and genetic background of the rye (Secale cereale L.) tissue
      culture response.
AB  - Rye is one of the most important crops in Eastern and Northern Europe. Despite
      the numerous beneficial features of rye, its annual production decreases
      successively which correlates with the lack of progress in its breeding compared
      with other cereals. Biotechnological methods could effectively improve the
      breeding of rye. However, their application is highly limited by the absence of
      an efficient procedure for plant regeneration in vitro, since rye is one of the
      most recalcitrant cereals with regard to the tissue culture response (TCR), and
      successful regeneration is highly dependent on genotype. Efforts to understand
      the genetic mechanisms controlling TCR of rye have elucidated some basic aspects,
      and several genes and genome regions controlling this trait have been identified.
      The aim of this review is to summarize the limited current knowledge of this
      topic.

PMID- 23007689
TI  - The interaction of banana MADS-box protein MuMADS1 and ubiquitin-activating
      enzyme E-MuUBA in post-harvest banana fruit.
AB  - KEY MESSAGE : The interaction of MuMADS1 and MuUBA in banana was reported, which
      will help us to understand the mechanism of the MADS-box gene in regulating
      banana fruit development and ripening. The ubiquitin-activating enzyme E1 gene
      fragment MuUBA was obtained from banana (Musa acuminata L.AAA) fruit by the yeast
      two-hybrid method using the banana MADS-box gene MuMADS1 as bait and 2-day post
      harvest banana fruit cDNA library as prey. MuMADS1 interacted with MuUBA. The
      interaction of MuMADS1 and MuUBA in vivo was further proved by bimolecular
      fluorescence complementation assay. Real-time quantitative PCR evaluation of
      MuMADS1 and MuUBA expression patterns in banana showed that they are highly
      expressed in the ovule 4 stage, but present in low levels in the stem, which
      suggests a simultaneously differential expression action exists for both MuMADS1
      and MuUBA in different tissues and developmental fruits. MuMADS1 and MuUBA
      expression was highly stimulated by exogenous ethylene and suppressed by 1
      methylcyclopropene. These results indicated that MuMADS1 and MuUBA were co
      regulated by ethylene and might play an important role in post-harvest banana
      fruit ripening.

PMID- 23007690
TI  - Prognostic impact of pretherapeutic laboratory values in head and neck cancer
      patients.
AB  - PURPOSE: The high comorbidity in patients with head and neck cancer (HNC) is
      mainly caused by the high incidence of tobacco and alcohol abuse and has direct
      impact on overall survival. We investigated whether HNC and its comorbidity also
      influence routine laboratory values and whether these values have influence on
      overall survival. METHODS: A retrospective cohort of 261 patients with primary
      squamous cell carcinoma of the oral cavity, pharynx, or larynx diagnosed between
      2001 and 2006 with a complete set of pretherapeutic laboratory values was
      identified. The influence of standard oncological parameters, comorbidity, and
      each laboratory value on overall survival (OS) was investigated in univariate and
      multivariate analyses. RESULTS: Two-thirds of patients were active smokers and
      about one half reported high alcohol consumption. 40 % of patients had severe
      comorbidity according to Charlson comorbidity index. The most frequent laboratory
      pathologies were elevated C-reactive protein (CRP) values (66 %), impaired liver
      enzymes (30-50 %), decreased urea levels (33 %), leukocytosis (20 %), and anemia
      (10 %). In multivariate analysis for OS, a comorbidity index >=5 (Hazard ratio
      [HR], 2.008; 95 % confidence interval [CI], 1.117-3.610; p = 0.020), high CRP
      level (HR, 2.469; CI, 1.414-4.310; p = 0.001), and abnormal low red-cell count
      (HR, 2.525; CI, 1.250-5.102; p = 0.010) were independent prognostic variables.
      CONCLUSIONS: Comorbidity reflected by pathologic laboratory values is a major
      issue in HNC patients. Several pretherapeutic laboratory values have prognostic
      relevance for overall survival in HNC patients.

PMID- 23007692
TI  - Potential for simplification of HIV treatment with boosted protease inhibitor
      monotherapy.
AB  - BACKGROUND: Previous studies have evaluated the simplification of HIV treatment
      with ritonavir-boosted protease inhibitor monotherapy, demonstrating acceptable
      efficacy and advantages such as avoidance of the adverse effects of reverse
      transcriptase inhibitors. To achieve the best results, patients should be
      appropriately selected for this therapy. OBJECTIVE: The purpose of this study was
      to estimate the proportion of HIV patients suitable for boosted protease
      inhibitor monotherapy according to clinical trial criteria. Setting The study was
      conducted in the outpatient hospital pharmacy service of the Complejo
      Hospitalario de Navarra in northern Spain. METHOD: A retrospective analysis was
      performed on data from 635 adults on antiretroviral therapy. The eligibility
      criteria were: (1) >18 years of age; (2) prior triple-drug antiretroviral
      regimen; (3) durability of current treatment >18 months; (4) viral load <400
      copies/mL over the 18 months before evaluation and <50 copies/mL over the last 6
      months; (5) CD4 count >=250 cells/MUL; (6) CD4 count nadir >100 cells/MUL; (7) no
      previous virological failure under prior protease inhibitor-based regimen; (8)
      absence of co-infection with hepatitis B virus; (9) absence of HIV-related
      neurological disease; and (10) adherence >95 %. The average cost of the current
      treatment was calculated for patients who met all criteria, as well as the
      potential economic impact of simplification to monotherapy. MAIN OUTCOME MEASURE:
      Number of patients meeting all criteria for simplification to monotherapy
      according to clinical trial standards. RESULTS: One hundred and three patients
      (16.5 %) met the clinical trial criteria for protease inhibitor monotherapy. One
      hundred and fifty patients (24 %) failed to fulfil only one of the conditions.
      Fifty-four percent of the patients who met all of the criteria had been treated
      for more than 10 years. The average saving per patient per year was <euro>2,850
      <euro>3,400. CONCLUSION: This treatment strategy represents a realistic, albeit
      minority, option. Fulfilment of the above conditions should be the basis for
      simplification to protease inhibitor monotherapy, though the final decision
      depends on clinical criteria and patient preferences assessed by the attending
      physician. Further studies are needed to confirm long-term safety and efficacy.

PMID- 23007693
TI  - The effect of pharmacotherapeutic counseling on readmissions and emergency
      department visits.
AB  - OBJECTIVE: To evaluate the impact of pharmacotherapeutic counseling on the rates
      and causes of 30-day post-discharge hospital readmissions and emergency
      department visits. SETTING: The study was conducted at the Medical Clinic of
      University Hospital Dubrava, Zagreb, Croatia. METHODS: The study included elderly
      patients prescribed with two or more medications for the treatment of chronic
      diseases. The patients randomized into the intervention group received pre
      discharge counseling by the clinical pharmacologist about each prescribed
      medication. The control group received no counseling. MAIN OUTCOME MEASURES: The
      rates and causes of 30-day postdischarge hospital readmissions and emergency
      department visits. Medication compliance was also evaluated, using the pill count
      method. RESULTS: A total of 160 patients were randomly selected for the study. No
      significant difference was found in the readmission and emergency department
      visit rates between the intervention and control groups (p = 0.224). There were
      34.9 % more compliant patients in the intervention group. Significantly more non
      compliant patients in the control group were readmitted or visited emergency
      department because of the disease progression (p = 0.031). In the intervention
      group, significantly more patients were readmitted or visited emergency
      department because of an adverse drug reaction (p = 0.022). CONCLUSION:
      Pharmacotherapeutic counseling can reduce readmission and emergency department
      visit rates for disease progression. Improved patient knowledge about adverse
      drug reactions could be the reason for increased rates of readmissions and
      emergency department visits due to adverse drug reactions in the intervention
      group.

PMID- 23007694
TI  - Nurse staffing, RN mix, and assault rates on psychiatric units.
AB  - The association between nurse staffing and patient violence on psychiatric units
      is unclear, and the association between nursing skill mix and violence has not
      been studied. Monthly data on physical/sexual assaults by patients against others
      were obtained for 351 adult psychiatric units. Total and injury assault rates
      were modeled as dependent variables using hierarchical Poisson regression, with
      total staffing and registered nurse (RN) mix as predictors. Assault rates were
      12% higher per additional nursing hour per patient day but 6% lower per 5-point
      increase in percent of hours provided by RNs. In cubic spline models fit to
      explore nonlinear staffing-violence associations, assault rates increased with
      staffing through most of its range but began to decline at very high levels.

PMID- 23007695
TI  - Effect of an event occurring over time and confounded by health status:
      estimation and interpretation. A study based on survival data simulations with
      application on breast cancer.
AB  - Estimating the prognostic effect of a time-dependent covariate could be tricky
      using a classical Cox model, despite adjustment on other known prognostic
      factors. This study evaluated and compared the performance of a Cox model
      including the covariate occurring over time as a time-dependent covariate and the
      so-called 'illness-death' multistate model, which is usually used to describe
      event-history data. We assess breast cancer prognosis related to a subsequent
      pregnancy occurring over time after cancer treatment in young women. We generated
      simulations. We considered constant and time-varying prognostic hazard ratios (
      HR(t)) between patients undergoing the intermediate event and those who did not.
      We used both the classical Cox model and the multistate model to estimate the
      prognostic effect of the intermediate event HR(t). We also used the latter to
      estimate the covariate effect on each transition (exp(beta(ij) )), thus helping
      to interpret HR(t) by taking into account the disease history. We applied these
      approaches to a female cohort treated and followed up in eight French Hospitals
      since 1990.

PMID- 23007697
TI  - Towards implementing the biopsychosocial factor in national health care systems:
      the role of postgraduate training in Austria.

PMID- 23007696
TI  - S100P is a metastasis-associated gene that facilitates transendothelial migration
      of pancreatic cancer cells.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the 5th most common cause of cancer
      death in the UK and the 4th in the US. The vast majority of deaths following
      pancreatic cancer are due to metastatic spread, hence understanding the
      metastatic process is vital for identification of critically needed novel
      therapeutic targets. An enriched set of 33 genes differentially expressed in
      common between primary PDAC and liver metastases, when compared to normal
      tissues, was obtained through global gene expression profiling. This metastasis
      associated gene set comprises transcripts from both cancer (S100P, S100A6, AGR2,
      etc.) and adjacent stroma (collagens type I, III, and V, etc.), thus reinforcing
      the concept of a continuous crosstalk between the two compartments in both
      primary tumours and their metastases. The expression of S100P, SFN, VCAN and
      collagens was further validated in additional primary PDACs and matched liver
      metastatic lesions, while the functional significance of one of the most highly
      expressed genes, S100P, was studied in more detail. We show that this protein
      increases the transendothelial migration of PDAC cancer cells in vitro, which was
      also confirmed in vivo experiments using a zebrafish embryo model. Thus S100P
      facilitates cancer cell intravasation/extravasation, critical steps in the
      hematogenous dissemination of pancreatic cancer cells.

PMID- 23007698
TI  - Direct puncture of the prosthetic bypass graft in the treatment of critical limb
      ischemia patient undergoing prior axillo-femoral bypass.
AB  - A 76-year-old man presented with a non-healing ischemic ulceration of the left
      foot. He had undergone left axillo-femoral bypass surgery 4 years previously.
      Diagnostic angiography showed total occlusion from the left common iliac to the
      common femoral artery and the anterior and posterior tibial artery as well as
      severe stenosis of the superficial femoral and peroneal artery. Because there
      were no other access sites except for the axillo-femoral bypass graft, we
      performed endovascular therapy (EVT) by direct puncture of this bypass graft.
      Here, we have described the utility of direct puncture of axillo-femoral
      prosthetic bypass graft for EVT of the infrainguinal arteries.

PMID- 23007699
TI  - Easy introduction of maleimides at different positions of oligonucleotide chains
      for conjugation purposes.
AB  - [2,5-Dimethylfuran]-protected maleimides were placed at both internal positions
      and the 3'-end of oligonucleotides making use of solid-phase synthesis
      procedures. A new phosphoramidite derivative and a new solid support
      incorporating the protected maleimide moiety were prepared for this purpose. In
      all cases maleimide deprotection (retro-Diels-Alder reaction) followed by
      reaction with thiol-containing compounds afforded the target conjugate.

PMID- 23007700
TI  - Disease mechanisms in MS: A role for sodium channels in regulation of macrophage
      mediated pathology in multiple sclerosis lesions.

PMID- 23007701
TI  - Alzheimer disease: from inherited to sporadic AD-crossing the biomarker bridge.
AB  - Whether dominantly inherited variants of Alzheimer disease (AD) and 'sporadic'
      forms exhibit similar pathophysiological and biomarker signatures remains
      unresolved. A landmark study has proposed a biomarker progression model of
      dominantly inherited AD, but a complex systems biology and physiology approach is
      required to translate these findings to sporadic disease.

PMID- 23007703
TI  - Metal self-recognition: a pathway to control the formation of dihelicates and
      mesocates.
AB  - We have studied the factors that affect the formation of different
      metallosupramolecular architectures by metal direct self-assembly. A synthetic
      route has been developed to obtain mesocates or dihelicates selectively. For this
      purpose a series of five bisthiosemicarbazone ligands derived from 1,3
      diacetylbenzene were designed and synthesised. Namely H(2)L(Me), H(2)L(Et),
      H(2)L(Ph), H(2)L(PhN) and H(2)L(PhOMe) with different substituents on the 4-N
      terminal position of the thiosemicarbazone strands. The Co(II), Zn(II) and Cd(II)
      complexes of these ligands were prepared by an electrochemical procedure.
      Crystallographic studies revealed the formation of mesocates for Co(II) and
      Zn(II) metal ions whereas the Cd(II) complexes gave a bishelical supramolecular
      structure. Therefore these bisthiosemicarbazone ligands enable the selective
      isolation of mesocate or dihelicate complexes by using a specific metal ion.

PMID- 23007702
TI  - Progressive multiple sclerosis: pathology and pathogenesis.
AB  - Major progress has been made during the past three decades in understanding the
      inflammatory process and pathogenetic mechanisms in multiple sclerosis (MS).
      Consequently, effective anti-inflammatory and immunomodulatory treatments are now
      available for patients in the relapsing-remitting stage of the disease. This
      Review summarizes studies on the pathology of progressive MS and discusses new
      data on the mechanisms underlying its pathogenesis. In progressive MS, as in
      relapsing-remitting MS, active tissue injury is associated with inflammation, but
      the inflammatory response in the progressive phase occurs at least partly behind
      the blood-brain barrier, which makes it more difficult to treat. The other
      mechanisms that drive disease in patients with primary or secondary progressive
      MS are currently unresolved, although oxidative stress resulting in mitochondrial
      injury might participate in the induction of demyelination and neurodegeneration
      in both the relapsing-remitting and progressive stages of MS. Oxidative stress
      seems to be mainly driven by inflammation and oxidative burst in microglia;
      however, its effects might be amplified in patients with progressive MS by age
      dependent iron accumulation in the brain and by mitochondrial gene deletions,
      triggered by the chronic inflammatory process.

PMID- 23007704
TI  - Identification of recurrence-related genes by integrating microRNA and gene
      expression profiling of gastric cancer.
AB  - We previously analyzed the microRNA (miRNA) expression pattern in gastric cancer
      with and without recurrence and obtained 17 differentially expressed miRNAs with
      potential to predict recurrence risk for GC patients. In the present study, we
      aimed to investigate recurrence-related genes which may be regulated by the
      differentially expressed miRNAs identified in our prior research. Three different
      miRNA target gene databases (miRanda, TargetScan and PicTar) were used for
      searching the potential genes regulated by miRNAs. A combination was performed
      between miRNA target genes and recurrence-related gene expression profiling.
      Three bioinformatics algorithms (PAM, SVM and RF) were used to feature recurrence
      related gene selection. In addition, we validated the expression levels of the
      genes in GC patients using real-time PCR. A total of 3,263 genes were identified
      as potential targets of 17 miRNAs. We identified 2,736 differential expressed
      genes using the SAM method based on 22K oligo microarray data which included 7
      recurrence and 4 without recurrence GC samples. Combining the target genes
      regulated by miRNAs and the differentially expressed genes between recurrence and
      non-recurrence groups, we identified 228 differential genes for further study.
      Finally, we identified HNRPA0 and PRDM4 as risk biomarkers of GC patients, which
      were regulated by hsa-miR-194 and hsa-miR-373, respectively. Our data indicated
      that HNRPA0 and PRDM4 may be involved in the recurrence process of GC and have
      potential to act as new prognostic biomarkers in predicting recurrence risk for
      gastric cancer patients.

PMID- 23007705
TI  - HIV and associated risk factors among male clients of female sex workers in a
      Chinese border region.
AB  - BACKGROUND: Male clients of female sex workers (FSWs) serve as a potential bridge
      of human immunodeficiency virus (HIV) to the general population. Little is known
      about the characteristics and risk factors for HIV infection among male clients
      patronizing FSWs in Hekou County, Yunnan Province in southern China bordering
      with Vietnam. METHODS: Male clients were recruited through outreach of study
      staff, referrals by Vietnamese FSWs and their bosses, and snowball sampling. Each
      participant completed a questionnaire survey and donated a blood specimen to test
      for HIV, herpes simplex virus type 2 (HSV-2), and syphilis. Logistic regression
      models were fitted to identify factors associated with HIV infection. RESULTS:
      Among 306 participants, 28 (9.2%) were HIV positive, 81 (26.5%) were HSV-2
      positive, and none was infected with syphilis. Approximately half (n = 149,
      49.2%) reported always using condoms with sex workers in the past year; 36
      (11.8%) reported a history of injection drug use (IDU). Compared with HIV
      negative men, HIV-positive men were more likely to have a history of IDU (64.3%
      vs. 6.5%) and be coinfected with HSV-2 (50.0% vs. 24.1%). CONCLUSIONS: IDU was
      the most salient risk factor for HIV infection in this study, which suggests that
      male clients may acquire HIV from routes other than commercial sex, but the
      significance of HSV-2 infection indicates that sexual transmission is also of
      concern. HIV prevention intervention programs for this often ignored and hard-to
      reach risk group should be two-pronged, addressing both drug use and commercial
      sex.

PMID- 23007706
TI  - A prospective event-level analysis of condom use experiences following STI
      testing among patients in three US cities.
AB  - BACKGROUND: This study prospectively assessed and compared the incidence of
      condom use errors/problems among clinic patients testing positive for one or more
      of 3 sexually transmitted diseases (STDs) and those testing negative. The study
      also identified event-level condom use errors associated with condom breakage and
      slippage during sex. METHODS: Enrolled clinic patients (N = 928) were tested for
      3 STDs, then patients electronically recorded sexual intercourse and condom use
      behaviors daily for up to 6 months. Data were available on condom use errors and
      problems for the >10,000 sex events involving condoms. Assessed errors/problems
      were as follows: (1) not using a new condom, (2) allowing condoms to contact
      sharp objects, (3) not using condoms from start to finish of sex, (4) condoms
      drying out, (5) erection loss during condom use, (6) breakage, (7) slippage
      during sex, and (8) slippage after sex. Because the event-level measures were
      correlated within individual, generalized estimation equation models were used
      for analyses. RESULTS: All 8 forms of errors/problems with condom use occurred,
      with varying levels of frequency, without significant differences by baseline STD
      status for either men or women. Condom breakage was associated with contact with
      sharp objects (P < 0.0001) and drying out (P < 0.0001). Slippage during sex was
      associated with erection loss (P < 0.0001) and drying out (P < 0.0001).
      CONCLUSION: Subsequent to STD evaluation, much of the sex occurring with the use
      of a condom may not confer adequate protection. Problems found to be associated
      with condom breakage and slippage are potentially amenable to counseling
      interventions.

PMID- 23007707
TI  - Primary cutaneous cryptococcosis of the penis.
AB  - Primary cutaneous cryptococcosis is characterized by skin lesions confined to one
      body region, without evidence of simultaneous dissemination. Skin lesions
      frequently occur in immunocompromised patients. We report a case of primary
      cutaneous cryptococcosis in an immunocompetent patient affecting genital area
      successfully treated with oral itraconazole.

PMID- 23007709
TI  - Systematic review of randomized trials of treatment of male sexual partners for
      improved bacteria vaginosis outcomes in women.
AB  - BACKGROUND: Bacterial vaginosis (BV) affects 10% to 30% of women and recurs in
      15% to 30% within 3 months after treatment. BV is not considered an sexually
      transmitted infection, and treatment of the male sexual partner is not
      recommended. This recommendation is based on the results of 6 randomized
      controlled trials (RCTs) of male partner treatment for reducing BV recurrence,
      which did not find a uniformly beneficial effect. These results are incongruous
      with epidemiologic and microbiologic data suggesting a sexually transmissible
      component of BV. In light of this disconnect, the 6 RCTs of male treatment were
      reviewed to assess validity. METHODS: Trials are summarized according to
      Consolidated Standards of Reporting Trials guidelines. Absolute differences and
      risk ratios with binomially obtained 95% confidence intervals were estimated.
      Post hoc power analyses determined the probability of rejecting the null
      hypothesis for observed relative effect sizes and for the smallest relative
      effect size detectable with >= 80% power. RESULTS: Each of the 6 RCTs had
      significant flaws: randomization methods were either overtly deficient or
      insufficiently reported; 5 RCTs used suboptimal treatment regimens in women;
      adherence to treatment in women was not reported in any trial, and adherence in
      men was reported in only 2 trials; all 6 trials had limited power. None assessed
      whether antibiotic treatment affected the penile microbiota. CONCLUSIONS:
      Although the RCT is the gold standard for assessing efficacy, biased results can
      mislead decision making. By current standards, it is unlikely that the results of
      any of these trials would be considered conclusive. Specific recommendations are
      made to examine whether BV-associated bacteria may be sexually transferred.

PMID- 23007708
TI  - Association between Trichomonas vaginalis and vaginal bacterial community
      composition among reproductive-age women.
AB  - OBJECTIVES: Some vaginal bacterial communities are thought to prevent infection
      by sexually transmitted organisms. Prior work demonstrated that the vaginal
      microbiota of reproductive-age women cluster into 5 types of bacterial
      communities; 4 dominated by Lactobacillus species (L. iners, L. crispatus, L.
      gasseri, L. jensenii) and 1 (termed community state type (CST) IV) lacking
      significant numbers of lactobacilli and characterized by higher proportions of
      Atopobium, Prevotella, Parvimonas, Sneathia, Gardnerella, Mobiluncus, and other
      taxa. We sought to evaluate the relationship between vaginal bacterial
      composition and Trichomonas vaginalis. METHODS: Self-collected vaginal swabs were
      obtained cross-sectionally from 394 women equally representing 4 ethnic/racial
      groups. T. vaginalis screening was performed using PCR targeting the 18S rRNA and
      beta-tubulin genes. Vaginal bacterial composition was characterized by
      pyrosequencing of barcoded 16S rRNA genes. A panel of 11 microsatellite markers
      was used to genotype T. vaginalis. The association between vaginal microbiota and
      T. vaginalis was evaluated by exact logistic regression. RESULTS: T. vaginalis
      was detected in 2.8% of participants (11/394). Of the 11 T. vaginalis-positive
      cases, 8 (72%) were categorized as CST-IV, 2 (18%) as communities dominated by L.
      iners, and 1 (9%) as L. crispatus-dominated (P = 0.05). CST-IV microbiota were
      associated with an 8-fold increased odds of detecting T. vaginalis compared with
      women in the L. crispatus-dominated state (OR: 8.26, 95% CI: 1.07-372.65). Seven
      of the 11 T. vaginalis isolates were assigned to 2 genotypes. CONCLUSION: T.
      vaginalis was associated with vaginal microbiota consisting of low proportions of
      lactobacilli and high proportions of Mycoplasma, Parvimonas, Sneathia, and other
      anaerobes.

PMID- 23007710
TI  - Dual ErbB1 and ErbB2 receptor tyrosine kinase inhibition exerts synergistic
      effect with conventional chemotherapy in pancreatic cancer.
AB  - Patient survival in pancreatic cancer remains poor with gemcitabine (GEM)-based
      regimens. The target specific molecular agent lapatinib, a dual ErbB1 and ErbB2
      receptor tyrosine kinase inhibitor, has shown significant activity against ErbB1
      and ErbB2-expressing tumors. Since pancreatic tumors frequently overexpress these
      proteins, we investigated its effects, both alone and in conjunction with 5-FU or
      GEM. The pancreatic cancer cell lines PANC-1 and AsPC were treated with varying
      doses of lapatinib in vitro. The effects on ErbB1/ErbB2 protein phosphorylation
      and on the cell survival protein survivin were determined by western blotting.
      Cytotoxicity was determined by MTT assay and apoptosis was measured using the
      caspase-3 colorimetric assay. Similar dose-response lapatinib experiments were
      conducted with varying concentrations of 5-FU or GEM and isobolograms were
      constructed to evaluate therapeutic synergy. Lapatinib inhibited protein
      phosphorylation in the range of 4-16 uM, a clinically achievable concentration.
      The lapatinib-treated cells showed a dose-dependent inhibition of cell
      proliferation and induction of apoptosis at the same concentrations that blocked
      ErbB1/ErbB2 phosphorylation. The addition of 5-FU or GEM to these cells resulted
      in synergistic effects. The lapatinib-treated cells also demonstrated
      downregulation of survivin. Simultaneous dual ErbB1 and ErbB2 receptor tyrosine
      kinase inhibition with lapatinib results in significant reduction of pancreatic
      cancer cell growth and proliferation. These effects occur at clinically
      achievable concentrations and are synergistic with the effects of 5-FU or GEM.
      These findings support the potential role of lapatinib in the treatment of
      pancreatic cancer.

PMID- 23007711
TI  - Harnessing monocyte-derived macrophages to control central nervous system
      pathologies: no longer 'if' but 'how'.
AB  - The central nervous system (CNS) tissues, including the brain, the eye, and the
      spinal cord, are immune-privileged, secluded from the circulation by a complex of
      barriers, and equipped with their own myeloid cell population, the resident
      microglia. Based on the classical perspective of immune-brain interactions and on
      the contribution of such interactions to the progression of multiple sclerosis,
      an autoimmune inflammatory disease of the CNS, infiltrating macrophages were
      traditionally viewed as an enemy of the nervous system. However, over the past
      two decades, research has revealed the pivotal role of monocyte-derived
      macrophages in CNS repair, and opened up a new era in understanding and treating
      CNS pathologies. Here, we gather current knowledge regarding macrophage broad
      spectrum of activities in the CNS, whose two poles correspond to the classical
      pro-inflammatory M1 and the 'alternatively-activated' M2 cells previously
      described in various non-CNS pathologies, and their diverse, multi-functional
      contribution in various neurological conditions, ranging from acute traumas to
      neurodegenerative disorders, and autoimmune diseases. The diverse functions are
      manifested by induction and resolution of inflammation as well as their
      involvement in neural tissue regeneration and renewal, matrix remodelling, debris
      clearance, and angiogenesis. A special focus is devoted to current evidence
      suggesting that resident microglia and infiltrating monocyte-derived macrophages
      are functionally non-redundant cell types. Taken together, these recent advances
      reveal a dramatic therapeutic opportunity for controlled harnessing of
      macrophages for repair of the damaged CNS following acute insults, in
      neurodegenerative conditions, and in psychiatric disorders.

PMID- 23007712
TI  - Nonanastomotic rupture of thoracic aortic Dacron graft treated by endovascular
      stent graft placement.
AB  - A 61-year-old man had a Stanford type A acute aortic dissection, and the total
      aortic arch was replaced with 22-mm knitted Dacron graft in 1996. In 2006, he
      underwent mitral valve replacement and tricuspid valve repair due to severe
      mitral and tricuspid valve regurgitation. Although preoperative computed
      tomography (CT) scan suggested pseudoaneurysm around the Dacron graft replaced
      with aortic arch, it could not be repaired concomitantly. Four months later, in
      view of the technical difficulties of an open surgical procedure, the prosthetic
      graft failure was repaired by endovascular stent graft consisting of a Gianturco
      Z stent covered with an UBE woven Dacron graft. However, during a follow-up,
      aneurysm sac diameter increased without any sings of endoleak in follow-up CT
      scans. Redo endovascular stent graft placement using a Gore-TAG device was
      performed. Subsequently, shrinkage of the pseudoaneurysmal sac could be observed.

PMID- 23007713
TI  - Exploring arterial smooth muscle Kv7 potassium channel function using patch clamp
      electrophysiology and pressure myography.
AB  - Contraction or relaxation of smooth muscle cells within the walls of resistance
      arteries determines the artery diameter and thereby controls flow of blood
      through the vessel and contributes to systemic blood pressure. The contraction
      process is regulated primarily by cytosolic calcium concentration
      ([Ca(2+)](cyt)), which is in turn controlled by a variety of ion transporters and
      channels. Ion channels are common intermediates in signal transduction pathways
      activated by vasoactive hormones to effect vasoconstriction or vasodilation. And
      ion channels are often targeted by therapeutic agents either intentionally (e.g.
      calcium channel blockers used to induce vasodilation and lower blood pressure) or
      unintentionally (e.g. to induce unwanted cardiovascular side effects). Kv7 (KCNQ)
      voltage-activated potassium channels have recently been implicated as important
      physiological and therapeutic targets for regulation of smooth muscle
      contraction. To elucidate the specific roles of Kv7 channels in both
      physiological signal transduction and in the actions of therapeutic agents, we
      need to study how their activity is modulated at the cellular level as well as
      evaluate their contribution in the context of the intact artery. The rat
      mesenteric arteries provide a useful model system. The arteries can be easily
      dissected, cleaned of connective tissue, and used to prepare isolated arterial
      myocytes for patch clamp electrophysiology, or cannulated and pressurized for
      measurements of vasoconstrictor/vasodilator responses under relatively
      physiological conditions. Here we describe the methods used for both types of
      measurements and provide some examples of how the experimental design can be
      integrated to provide a clearer understanding of the roles of these ion channels
      in the regulation of vascular tone.

PMID- 23007714
TI  - Lymphaticovenular bypass surgery for lymphedema management in breast cancer
      patients.
AB  - Historically, the reported incidence of upper extremity lymphedema in breast
      cancer survivors who have undergone axillary lymph node dissection has ranged
      from 9% to 41%. In the past 2 decades, sentinel lymph node biopsy has become
      popular as a way to minimize the morbidity associated with axillary dissection
      without compromising the cure rate for breast cancer patients. However, even with
      sentinel node biopsy, the postoperative incidence of upper limb lymphedema in
      breast cancer patients remains at 4-10%. Lymphedema occasionally emerges
      immediately after surgery but most often appears after a latent period. Obesity,
      postoperative seroma, and radiation therapy have been reported as major risk
      factors for upper extremity lymphedema, but the etiology of lymphedema is still
      not fully understood. Common symptoms of upper limb lymphedema are increased
      volume and weight of the affected limb and increased skin tension. The increased
      volume of the affected limb not only causes physical impairments in wearing
      clothes and in dexterity but also affects patients' emotional and mental status.
      Surgical management of lymphedema can be broadly categorized into physiologic
      methods and reductive techniques. Physiologic methods such as flap interposition,
      lymph node transfers, and lymphatic bypass procedures aim to decrease lymphedema
      by restoring lymphatic drainage. In contrast, reductive techniques such as direct
      excision or liposuction aim to remove fibrofatty tissue generated as a
      consequence of sustained lymphatic fluid stasis. Currently, microsurgical
      variations of lymphatic bypass, in which excess lymph trapped within the
      lymphedematous limb is redirected into other lymphatic basins or into the venous
      circulation, have gained popularity.

PMID- 23007715
TI  - Student impressions of an art therapy class.
AB  - Art therapy facilitates the expression of thoughts and feelings and thus may
      serve as a self-care strategy. This paper describes the implementation of an
      expressive art therapy class to teach self-care during a required sophomore level
      nursing wellness course and the outcomes of the class through the eyes of six
      students. While students were initially reluctant to engage in the activity, the
      shared stories revealed feelings of relaxation, empowerment, value clarification,
      and increased self-awareness. The implication for nursing education is that the
      integration of art therapy into curricula may serve as an effective strategy to
      teaching self-care and core professional values.

PMID- 23007716
TI  - The effects of slow-stroke back massage on minutes of nighttime sleep in persons
      with dementia and sleep disturbances in the nursing home: a pilot study.
AB  - PURPOSE: This pilot study tested the effects of a 3-minute slow-stroke back
      massage (SSBM) on total minutes of nighttime sleep on persons with dementia with
      sleep disturbances aged 65 years or older in the nursing home. DESIGN: Pilot
      randomized controlled trial. METHODS: Participants were randomized to an
      intervention group (n = 20) who received the 3-minute SSBM or a usual care
      control condition group (n = 20) who received usual bedtime care. Forty-eight
      hours of actigraphy data was recorded and analyzed on sleep variables at baseline
      and postintervention. FINDINGS: Descriptive statistics showed a 36-minute
      increase on minutes of nighttime sleep in the SSBM intervention group (46.1
      minutes) compared with the control group (10.32 minutes). Analysis of covariance
      did not reveal significant differences between the intervention and control
      groups on minutes of nighttime sleep, F(1, 37) = 1.90, p = .18, partial eta(2) =
      .05, or on other sleep variables. CONCLUSIONS: Dose-finding studies are needed to
      determine the duration of SSBM for sleep promotion. Findings from this pilot
      study suggest that SSBM may be an effective nursing intervention for sleep in
      persons with dementia in the nursing home, but further testing is needed to
      provide definitive results.

PMID- 23007717
TI  - Granulomatous variant of pigmented purpuric dermatosis.
AB  - Granulomatous pigmented purpuric dermatosis is a rare entity. Historically, it
      has been seen in Asians. In this article, we report the case of a white man with
      this unusual variant. A 65-year-old, white man presented with a 1-year history of
      asymptomatic purpuric to brown papules on both lower legs and more confluent on
      dorsum of feet. He had an underlying history of hypertension and hyperlipidemia.
      Skin biopsy revealed a granulomatous lympho-histocytary inflammatory infiltrate
      in papillary dermis and superficial reticular dermis with extravasation of red
      blood cells and siderophages. Periodic acid schiff (PAS), Giemsa and Ziehl
      Neelsen stains were negative. A diagnosis of granulomatous pigmented purpuric
      dermatosis was made. From the 10 cases reported of this granulomatous variant, 6
      were associated with hyperlipidemia. We report an additional case with this
      association.

PMID- 23007718
TI  - Upper urinary tract instillations in the treatment of urothelial carcinomas: a
      review of technical constraints and outcomes.
AB  - OBJECTIVES: The role of topical upper urinary tract instillation as adjuvant
      treatment after conservative management of urothelial carcinomas remains unclear.
      The aim of this article was to review available techniques and protocols proposed
      to treat urothelial carcinomas of the upper tract (UTUC). METHODS: Evidence
      acquisition on UTUC topical instillations was performed by a Medline search using
      combinations of the following key words: urothelial carcinomas; upper urinary
      tract; renal pelvis; ureter; adjuvant therapy; recurrence; bacillus Calmette
      Guerin (BCG); mitomycin C. A total of 36 publications were included in analysis.
      RESULTS: Different approaches have been reported for instillation of the upper
      tract (UT): percutaneous nephrostomy, retrograde catheterisation and vesico
      ureteral reflux. Currently, BCG and mitomycin C are the most commonly agents used
      for topical treatment of UTUC. A role for BCG in the management of UT carcinoma
      in situ (CIS) has been demonstrated in retrospective studies, although a
      definitive efficacy of adjuvant topical therapy after endoscopic resection of
      Ta/T1 tumours has not yet been proven. No individual study has shown a
      statistical improvement in survival and recurrence rates. CONCLUSION: Currently
      BCG instillation should be considered as first-line treatment for UT CIS managed
      conservatively in carefully selected patients. The place for adjuvant topical
      instillation after ablation of Ta/T1 tumours is less evident and should be
      evaluated on an individual basis.

PMID- 23007719
TI  - Temporal-envelope reconstruction for hearing-impaired listeners.
AB  - Recent studies suggest that normal-hearing listeners maintain robust speech
      intelligibility despite severe degradations of amplitude-modulation (AM) cues, by
      using temporal-envelope information recovered from broadband frequency-modulation
      (FM) speech cues at the output of cochlear filters. This study aimed to assess
      whether cochlear damage affects this capacity to reconstruct temporal-envelope
      information from FM. This was achieved by measuring the ability of 40 normal
      hearing listeners and 41 listeners with mild-to-moderate hearing loss to identify
      syllables processed to degrade AM cues while leaving FM cues intact within three
      broad frequency bands spanning the range 65-3,645 Hz. Stimuli were presented at
      65 dB SPL for both normal-hearing listeners and hearing-impaired listeners. They
      were presented as such or amplified using a modified half-gain rule for hearing
      impaired listeners. Hearing-impaired listeners showed significantly poorer
      identification scores than normal-hearing listeners at both presentation levels.
      However, the deficit shown by hearing-impaired listeners for amplified stimuli
      was relatively modest. Overall, hearing-impaired data and the results of a
      simulation study were consistent with a poorer-than-normal ability to reconstruct
      temporal-envelope information resulting from a broadening of cochlear filters by
      a factor ranging from 2 to 4. These results suggest that mild-to-moderate
      cochlear hearing loss has only a modest detrimental effect on peripheral,
      temporal-envelope reconstruction mechanisms.

PMID- 23007720
TI  - Vowel identification by amplitude and phase contrast.
AB  - Vowel identification is largely dependent on listeners' access to the frequency
      of two or three peaks in the amplitude spectrum. Earlier work has demonstrated
      that, whereas normal-hearing listeners can identify harmonic complexes with vowel
      like spectral shapes even with very little amplitude contrast between "formant"
      components and remaining harmonic components, listeners with hearing loss require
      greater amplitude differences. This is likely the result of the poor frequency
      resolution that often accompanies hearing loss. Here, we describe an additional
      acoustic dimension for emphasizing formant versus non-formant harmonics that may
      supplement amplitude contrast information. The purpose of this study was to
      determine whether listeners were able to identify "vowel-like" sounds using
      temporal (component phase) contrast, which may be less affected by cochlear loss
      than spectral cues, and whether overall identification improves when congruent
      temporal and spectral information are provided together. Five normal-hearing and
      five hearing-impaired listeners identified three vowels over many presentations.
      Harmonics representing formant peaks were varied in amplitude, phase, or a
      combination of both. In addition to requiring less amplitude contrast, normal
      hearing listeners could accurately identify the sounds with less phase contrast
      than required by people with hearing loss. However, both normal-hearing and
      hearing-impaired groups demonstrated the ability to identify vowel-like sounds
      based solely on component phase shifts, with no amplitude contrast information,
      and they also showed improved performance when congruent phase and amplitude cues
      were combined. For nearly all listeners, the combination of spectral and temporal
      information improved identification in comparison to either dimension alone.

PMID- 23007721
TI  - Grin and bear it! Neural consequences of a voluntary decision to act or inhibit
      action.
AB  - Action inhibition is an important part of everyday human behaviour. Most previous
      studies of action inhibition have focussed on stop-signals. Here, we consider the
      case where participants themselves decide to inhibit, or not inhibit, a prepotent
      action. Participants received electric stimulation that elicited an itchy feeling
      on the wrist. If they made a hand withdrawal movement, this would interrupt the
      stimulation, and halt the itch. In a factorial design, participants were given
      external instructions to withdraw their hand when they felt the itch, or to
      inhibit the natural withdrawal response, and bear the itch. In another condition,
      they were asked to internally choose between withdrawal and inhibition of
      withdrawal. Event-related potentials revealed differences between processing of
      the sensory consequences of internally decided and externally-instructed action
      and inhibition decisions. Specifically, potentials evoked by itchy stimuli were
      enhanced in internally decided inhibition trials, as compared to externally
      instructed inhibition trials. In contrast, processing of itchy stimuli was
      reduced in internally decided action trials, as compared to externally instructed
      action trials. These results show that internal decisions lead to different
      perceptual processing of the consequences of action and inhibition and suggest
      that features of decision processes can be measured via their consequences.

PMID- 23007722
TI  - Different effects of head tilt on ocular vestibular-evoked myogenic potentials in
      response to bone-conducted vibration and air-conducted sound.
AB  - The ocular vestibular-evoked myogenic potentials (oVEMPs) in response to air
      conducted sound (ACS) and bone-conducted vibration (BCV) have recently been used
      to assess otolith-ocular pathways in humans. Although the oVEMPs to BCV are
      considered to reflect the function of the utricle and superior vestibular
      pathway, the pathway of the oVEMPs to ACS remains controversial. In this study,
      we compared the effect of different head positions in the roll plane on oVEMPs in
      response to BCV and ACS in 20 normal subjects. Head tilt in the roll plane
      significantly increased the asymmetry ratio of oVEMPs to BCV (p < 0.01) but did
      not affect the asymmetry ratio of oVEMPs to ACS. Head tilt did not affect the
      latencies of oVEMPs to either BCV or ACS. Rotation of the body in the yaw plane
      while keeping the head straight ahead did not affect the asymmetry of oVEMPs to
      BCV (p > 0.6). These results suggest that oVEMPs to BCV reflect the activity of a
      different population of vestibular afferents to those which are active during
      oVEMPs to ACS.

PMID- 23007723
TI  - Functional relationship between cognitive representations of movement directions
      and visuomotor adaptation performance.
AB  - The aim of our study was to explore whether or not different types of learners in
      a sensorimotor task possess characteristically different cognitive
      representations. Participants' sensorimotor adaptation performance was measured
      with a pointing paradigm which used a distortion of the visual feedback in terms
      of a left-right reversal. The structure of cognitive representations was assessed
      using a newly established experimental method, the Cognitive Measurement of
      Represented Directions. A post hoc analysis revealed inter-individual differences
      in participants' adaptation performance, and three different skill levels
      (skilled, average, and poor adapters) have been defined. These differences in
      performance were correlated with the structure of participants' cognitive
      representations of movement directions. Analysis of these cognitive
      representations revealed performance advantages for participants possessing a
      global cognitive representation of movement directions (aligned to cardinal
      movement axes), rather than a local representation (aligned to each neighboring
      direction). Our findings are evidence that cognitive representation structures
      play a functional role in adaptation performance.

PMID- 23007725
TI  - Genetic characterization and phylogenetic analysis of Trypanosoma evansi in
      Iranian dromedary camels.
AB  - Whole blood samples were collected from 117 male clinically healthy Camelus
      dromedarius aged between 6 months to 18 years from several farms in Yazd Province
      of Iran. Trypanosoma evansi-affected camels were detected by Giemsa-stained blood
      smears, and the positive blood samples (4 out of 117) were submitted to PCR
      examination and phylogenetic analysis. Basic Local Alignment Search Tool data of
      the obtained complete internal transcribed spacer (ITS) sequences revealed that
      they corresponded to those of T. evansi, Thailand cattle isolate (AY912276) with
      the homology of 99 %. Both phylogenetic trees generated by ITS1 and complete ITS
      were unable to clearly show inter- and intraspecific genetic diversity of
      Trypanosoma spp. isolates. The phylogenetic tree inferred from the ITS2
      nucleotide sequences (569 bp) clearly showed the genetic diversity of the
      parasites. Phylogenetic and molecular analyses of this region showed that two
      distinct genotypes of T. evansi in Iranian dromedary camels are present. In
      contrast to the ITS1 and ITS2 regions, multiple alignment of the nucleotide
      sequence of the 5.8S rRNA showed a high degree of sequence conservation during
      evolution in various Trypanosoma spp.

PMID- 23007724
TI  - Cortical representation of different motor rhythms during bimanual movements.
AB  - The cortical control of bimanual and unimanual movements involves complex
      facilitatory and inhibitory interhemispheric interactions. We analysed the part
      of the cortical network directly related to the motor output by corticomuscular
      (64 channel EEG-EMG) and cortico-cortical (EEG-EEG) coherence and delays at the
      frequency of a voluntarily maintained unimanual and bimanual rhythm and in the 15
      30-Hz band during isometric contractions. Voluntary rhythms of each hand showed
      coherence with lateral cortical areas in both hemispheres and occasionally in the
      frontal midline region (60-80 % of the recordings and 10-30 %, respectively).
      They were always coherent between both hands, and this coherence was positively
      correlated with the interhemispheric coherence (p < 0.01). Unilateral movements
      were represented mainly in the contralateral cortex (60-80 vs. 10-30 %
      ipsilateral, p < 0.01). Ipsilateral coherence was more common in left-hand
      movements, paralleled by more left-right muscle coherence. Partial
      corticomuscular coherence most often disappeared (p < 0.05) when the
      contralateral cortex was the predictor, indicating a mainly indirect connection
      of ipsilateral/frontomesial representations with the muscle via contralateral
      cortex. Interhemispheric delays had a bimodal distribution (1-10 and 15-30 ms)
      indicating direct and subcortical routes. Corticomuscular delays (mainly 12-25
      ms) indicated fast corticospinal projections and musculocortical feedback. The 15
      30-Hz corticomuscular coherence during isometric contractions (60-70 % of
      recordings) was strictly contralaterally represented without any peripheral left
      right coherence. Thus, bilateral cortical areas generate voluntary unimanual and
      bimanual rhythmic movements. Interhemispheric interactions as detected by EEG-EEG
      coherence contribute to bimanual synchronization. This is distinct from the
      unilateral cortical representation of the 15-30-Hz motor rhythm during isometric
      movements.

PMID- 23007726
TI  - Description of advanced third-stage larvae of Gnathostoma lamothei Bertoni-Ruiz
      et al. 2005 (Nematoda: Gnathostomatidae) from experimental hosts and
      contributions to its life cycle.
AB  - The advanced third-stage larvae (AdvL(3)) of Gnathostoma lamothei was obtained
      from experimental hosts. Frogs Lithobates heckscheri and snakes Nerodia fasciata
      pictiventris were compatible hosts allowing optimal larval development. AdvL(3)
      are 4,487.94 MUm long, have two lateral cervical papillae between rows 10 and 16
      and an excretory pore at row 23. The average counts of the cephalic bulb hooklets
      from the four rows are 39.3, 43.3, 44.2, and 47.3. Larvae show an esophagus that
      represents 40 % of the body width. These findings indicate that amphibians and
      reptiles could be involved as G. lamothei natural hosts; nevertheless, their role
      as etiological agents of human gnathostomiasis is uncertain. This paper reports
      for the first time the taxonomic description of G. lamothei AdvL(3) obtained from
      experimental hosts and contributes to the understanding of its life cycle.

PMID- 23007727
TI  - Obesity, metabolic syndrome, and insulin resistance in urban high school students
      of minority race/ethnicity.
AB  - OBJECTIVES: To determine the point prevalences of metabolic syndrome (MetS) and
      its components among healthy weight, overweight, and obese inner-city public high
      school students, to compare the prevalences of MetS when using 2 different
      definitions (one with the impaired fasting glucose [IFG] level and the other with
      a homeostasis model assessment of insulin resistance [HOMA-IR] of 3.99 or higher
      to define the glucose regulation component), and to compare the degree to which
      HOMA-IR and fasting glucose level are associated with the other MetS components.
      DESIGN: Cross-sectional analysis. SETTING: Two New York City public high schools,
      from April 2008 through August 2011. PARTICIPANTS: Convenience sample of 1185
      high school youth, comprising predominantly Hispanic and African American
      students from low-income households, participating in The Banishing Obesity and
      Diabetes in Youth Project, a medical screening and education program. MAIN
      OUTCOME MEASURES: Prevalences of the following individual MetS components: IFG
      threshold, HOMA-IR, hypertension, central adiposity, hypertriglyceridemia, and
      low high-density lipoprotein cholesterol. Rates of MetSIFG and MetSHOMA-IR were
      also assessed. RESULTS: MetSIFG and MetSHOMA-IR point prevalences were both 0.3%
      in the healthy weight group; they were 2.6% and 5.9%, respectively, in the
      overweight group and were 22.9% and 35.1%, respectively, in the obese group (P <
      .05 for both). An IFG threshold of 100 mg/dL or higher was found in 1.0% of
      participants, whereas a HOMA-IR of 3.99 or higher was found in 19.5% of
      participants. CONCLUSIONS: An elevated HOMA-IR is much more sensitive than an IFG
      threshold in identifying adolescents with metabolic dysregulation. Using a HOMA
      IR threshold of 3.99 identifies more youth with MetS than using an IFG threshold
      of 100 mg/dL. In addition to increasing the sensitivity of MetS detection, HOMA
      IR has a much higher association with the other MetS components than the IFG
      threshold and may better reflect a unified underlying pathologic process useful
      to identify youth at risk for disease.

PMID- 23007728
TI  - Ectopic expression of a maize calreticulin mitigates calcium deficiency-like
      disorders in sCAX1-expressing tobacco and tomato.
AB  - Deregulated expression of an Arabidopsis H+/Ca2+ antiporter (sCAX1) in
      agricultural crops increases total calcium (Ca2+) but may result in yield losses
      due to Ca2+ deficiency-like symptoms. Here we demonstrate that co-expression of a
      maize calreticulin (CRT, a Ca2+ binding protein located at endoplasmic reticulum)
      in sCAX1-expressing tobacco and tomato plants mitigated these adverse effects
      while maintaining enhanced Ca2+ content. Co-expression of CRT and sCAX1 could
      alleviate the hypersensitivity to ion imbalance in tobacco plants. Furthermore,
      blossom-end rot (BER) in tomato may be linked to changes in CAX activity and
      enhanced CRT expression mitigated BER in sCAX1 expressing lines. These findings
      suggest that co-expressing Ca2+ transporters and binding proteins at different
      intracellular compartments can alter the content and distribution of Ca2+ within
      the plant matrix.

PMID- 23007730
TI  - Predictive abilities of the STOP-Bang and Epworth Sleepiness Scale in identifying
      sleep clinic patients at high risk for obstructive sleep apnea.
AB  - This study compared the predictive abilities of the STOP-Bang and Epworth
      Sleepiness Scale (ESS) for screening sleep clinic patients for obstructive sleep
      apnea (OSA) and sleep-disordered breathing (SDB). Forty-seven new adult patients
      without previous diagnoses of OSA or SDB were administered the STOP-Bang and ESS
      and were assigned to OSA or SDB risk groups based on their scores. STOP-Bang
      responses were scored with two Body Mass Index cut points of 35 and 30 kg/m(2)
      (SB35 and SB30). The tools' predictive abilities were determined by comparing
      patients' predicted OSA and SDB risks to their polysomnographic results. The SB30
      correctly identified more patients with OSA and SDB than the ESS alone. The ESS
      had the highest specificity for OSA and SDB.

PMID- 23007729
TI  - Direct interactions of ABA-insensitive(ABI)-clade protein phosphatase(PP)2Cs with
      calcium-dependent protein kinases and ABA response element-binding bZIPs may
      contribute to turning off ABA response.
AB  - Abscisic acid (ABA) signaling via the pyrabactin-resistant and related
      (PYR/PYL/RCAR) receptors begins with ABA-dependent inactivation of the ABA
      insensitive(ABI)-clade protein phosphatases(PP)2Cs, thereby permitting
      phosphorylation and activation of the Snf1-related (SnRK)2 clade of protein
      kinases, and activation of their downstream targets such as ABA-response element
      binding basic leucine zipper (bZIP) transcription factors (ABF/AREB/ABI5 clade).
      Several of these are also activated by calcium-dependent protein kinases such as
      CPK11. Turning off ABA response requires turnover and/or inactivation of these
      transcription factors, which could result from their dephosphorylation. To
      address the hypothesis that the ABI-clade PP2Cs regulate the bZIPs directly, in
      addition to their indirect effects via SnRKs, we have assayed interactions
      between multiple members of the ABF/AREB clade and the PP2Cs by yeast two-hybrid,
      in vitro phosphatase, and bimolecular fluorescence complementation assays. In
      addition, we have expanded the list of documented specific interactions among
      these bZIP proteins and the kinases that could activate them and found that some
      PP2Cs can also interact directly with CPK11. These studies support specific
      interactions among kinases, phosphatases and transcription factors that are co
      expressed in early seedling development.

PMID- 23007731
TI  - Gamma-aminobutyric acid binds to GABAb receptor to inhibit cholangiocarcinoma
      cells growth via the JAK/STAT3 pathway.
AB  - BACKGROUND: Gamma-aminobutyric acid (GABA) has been reported to inhibit the
      growth of cholangiocarcinoma QBC939 cells, but the mechanisms are still not fully
      understood. AIMS: To explore the mechanisms of the anti-cancer effect of GABA on
      QBC939 cells. METHODS: An initial immunohistochemistry study of the expressions
      of GABA receptors in cholangiocarcinoma tissues was followed by the culture and
      treatment of QBC939 cells for 48 h with GABA, GABA + bicuculine (GABAA receptor
      antagonist), GABA + phaclofen (GABAB receptor antagonist), and GABA + AG490
      (Janus Kinase inhibitor). MTT and Annexin V-FITC/PI binding assays were used to
      determine the proliferation and apoptosis of the QBC939 cells. The expression of
      the signal transducer and activator of transcription 3 (STAT3) and phosphorylated
      STAT3 (Tyr705) [p-STAT3 (Tyr705)] was evaluated by the western blot assay. The
      effect of GABA on the growth of QBC939 xenograft tumors in athymic nu/nu mice was
      examined, and p-STAT3 (Tyr705) expression in xenograft tumors was detected by
      immunohistochemistry. RESULTS: A significant difference was only observed in
      GABAB receptor expression between cholangiocarcinoma and normal bile tissues. The
      MTT and Annexin V-FITC/PI assays showed that the antiproliferative and
      proapoptotic effects of GABA on QBC939 cells could be antagonized by phaclofen
      and AG490, but not bicuculine. GABA significantly down-regulated p-STAT3 (Tyr705)
      expression; this action was also antagonized by phaclofen and AG490. GABA also
      effectively inhibited xenograft tumor growth, and p-STAT3 (Tyr705) expression was
      significantly decreased in GABA-treated xenograft tumors. CONCLUSIONS: GABA may
      inhibit the growth of cholangiocarcinoma QBC939 cells through the GABAB receptor,
      and the anti-cancer effects may be partly mediated via the JAK/STAT3 pathway.

PMID- 23007732
TI  - Radiofrequency-assisted versus clamp-crushing parenchyma transection in cirrhotic
      patients with hepatocellular carcinoma: a randomized clinical trial.
AB  - BACKGROUND: Surgical resection remains the optimal therapy for cirrhotic patients
      with hepatocellular carcinoma (HCC) that are not suitable for liver
      transplantation (LT). Recently, various innovative techniques for liver resection
      have been developed. AIM: The aim of the study was to compare radiofrequency
      assisted parenchyma transection (RF-PT) with the traditional clamp-crushing (CC)
      technique to explore the preferred therapy in cirrhotic patients with HCC.
      METHODS: From January 2009 to December 2010, 75 cirrhotic patients with HCC who
      underwent hepatectomy were randomized to RF-PT (group 1, n = 38) or CC-PT (group
      2, n = 37) groups. The primary endpoint was intraoperative blood loss. The
      secondary endpoints included hepatic transection time, total operating time,
      postoperative morbidity, mortality, length of intensive care unit and hospital
      stays, and liver function. RESULTS: The characteristics of the two patient groups
      were closely matched. The Pringle maneuver was not used in RF-PT patients. The
      blood loss of the RF-PT group, total or during transection, was significantly
      lower than that of the CC-PT group (385 vs. 545 ml, p = 0.001; 105 vs. 260 ml, p
      = 0.000, respectively). Compared with CC-PT patients, the morbidity of the RF-PT
      group was lower though not statistically significant (28.9 vs. 38.8 %, p =
      0.197). One death occurred in the RF-PT group 12 days postoperative due to a
      large area cerebral embolism. CONCLUSION: RF-PT is a safe and feasible surgical
      resection method for patients with cirrhosis and concomitant HCC. In addition, RF
      PT results in lower blood loss and lower morbidity than the CC technique during
      liver resection.

PMID- 23007733
TI  - Percutaneous endoscopic gastrostomy in cancer patients: predictors of 30-day
      complications, 30-day mortality, and overall mortality.
AB  - BACKGROUND: Cancer patients benefit from percutaneous endoscopic gastrostomy
      (PEG) in many ways including nutritional support and venting in cases of
      malignant obstruction. Lack of high-quality studies with adequate follow-up has
      led to limited information regarding risk stratification and predictors of
      morbidity and mortality. AIMS: Elucidate predictors of complications and
      mortality with long-term follow-up in cancer patients undergoing PEG. METHOD:
      Retrospective review of all patients undergoing PEG placement at MD Anderson
      Cancer Center from January 1, 2004 to December 31, 2006. Statistical analysis
      included descriptive statistics, Kaplan-Meier survival estimates, and Cox
      proportional hazards regression analyses. RESULTS: A total of 218 subjects
      underwent PEG. Those with American Society of Anesthesiology (ASA) scores of 4,
      4E, or 5E were at significant risk of a major complication in the first 30 days.
      Multivariate analysis revealed ASA scores >=4, elevated WBC count, and advanced
      tumor stage to be independent predictors of mortality in the first 30 days and
      INR >1.5 and diversion/venting as an indication for PEG placement to be
      independent predictors of overall mortality. CONCLUSIONS: Patients with high
      baseline illness severity are more likely to have complications and are at
      increased risk of mortality after PEG. Our study results suggest that particular
      attention be directed to ASA score, INR, WBC counts, transfusion requirements,
      presence of advanced malignancies, and the indication for PEG placement when
      determining risk of complications or death. Patients undergoing venting PEG are
      expected to have short post-PEG survival but improvement in quality of life
      likely justifies the risks associated with PEG placement.

PMID- 23007734
TI  - Increased serum levels of carbohydrate antigen 19-9 and outcomes in primary
      sclerosing cholangitis patients without cholangiocarcinoma.
AB  - BACKGROUND: Carbohydrate antigen 19-9 (CA 19-9) is the serum marker used to
      diagnose cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis
      (PSC). AIM: We investigated long-term outcomes in patients with PSC and elevated
      CA 19-9 levels without CCA. METHODS: A total of 166 PSC patients with serum
      levels of CA 19-9 without CCA followed at a single center from 1998 to 2011 were
      included. Patients with and without elevated CA 19-9 levels (greater than 129
      U/ml) were compared. RESULTS: Fifty-two (31.3 %) of the 166 patients with PSC
      without CCA had elevated serum CA-19-9. Patients with elevated CA-19-9 were
      followed for a mean of 4 years and 12 (23.1 %) died. They were more likely to
      have higher PSC risk score (1.67 +/- 1.30 vs. 0.91 +/- 1.53, p = 0.003) and
      dominant strictures (31 (59.6 %) vs. 21 (18.4 %), p < 0.001). In 17/52 (32.7 %)
      of patients with elevated CA-19-9, no etiology was identified; cholestasis and
      cholangitis were associated with elevated levels in 24/52 (48.1 %) and 11/52
      (21.2 %), respectively. There were 32 of 52 (62.5 %) that underwent orthotopic
      liver transplantation (OLT) in elevated CA 19-9 group compared to 66/114 (56.9 %)
      without (p = 0.66). The median OLT-free survival with elevated CA 19-9 was 9
      years from PSC diagnosis compared to 14 years without. Although there was a
      trend, there was no significant difference in the OLT-free survival on Kaplan
      Meier analysis (log rank p = 0.12). CONCLUSIONS: Thirty-two percent of patients
      with PSC had elevated serum CA 19-9 in the absence of CCA. There was a trend
      towards shorter OLT-free survival in PSC patients with elevated CA-19-9.

PMID- 23007735
TI  - Metal-free intramolecular aminofluorination of alkenes mediated by
      PhI(OPiv)2/hydrogen fluoride-pyridine system.
AB  - A convenient, metal-free intramolecular aminofluorination of alkenes has been
      developed. Employing readily available PhI(OPiv)(2) and hydrogen fluoride
      pyridine in the presence of BF(3).OEt(2), tosyl-protected pent-4-en-1-amines were
      converted to 3-F-piperidines in one step in good yields as well as high
      stereoselectivity.

PMID- 23007736
TI  - Changes in serum parameters associated with iron metabolism in male rat exposed
      to lead.
AB  - Due to the severe hazardous influences of lead (Pb(2+)) on iron-related diseases,
      the effects of Pb(2+) on serum parameters associated with iron metabolism have
      been studied in this project. Male Wistar rats weighing 200-250 g were treated
      with Pb(2+) for the short and long period of times. The animals received daily
      intraperitoneal injection of 100 mg Pb(2+) kg(-1) body weight (BW) for 5 days and
      4 mg kg(-1) BW of Pb(2+) for 30 and 45 days, respectively. The results show that
      when animals were treated with both low and high concentrations of Pb(2+), serum
      iron concentration decreased markedly, by 23.2, 32.8, and 39.9 %, while the sera
      TIBC and transferrin concentrations increased significantly (p < 0.05). Following
      short- and long-term exposures to Pb(2+), the percentage of serum transferrin
      saturation was also decreased in comparison with the untreated control group (p <
      0.05). Concentrations of serum copper and ceruloplasmin following Pb(2+)
      treatments also reduced significantly (p < 0.05). The percentage of hematocrit
      and hemoglobin levels was reduced (p < 0.05) in all Pb(2+)-treated animals in
      comparison with the controls. These results suggest that Pb(2+) changes the serum
      parameters related to iron metabolism, which may play an important role in
      producing iron-related diseases.

PMID- 23007737
TI  - miRNA expression profile of colon cancer stem cells compared to non-stem cells
      using the SW1116 cell line.
AB  - Colorectal cancer (CRC) is one of the major causes of cancer-related mortality
      worldwide. Recent studies revealed that there is a relationship between CRC
      occurrence and microRNA (miRNA) function. Stem cells are a type of cells that
      have the ability to self-renew and to proliferate extensively while maintaining
      the undifferentiated state. Cancer stem cells (CSCs) are closely linked to tumor
      recurrence and metastasis. To this end, we evaluated the miRNA expression
      differences between colon CSCs and non-stem cells using the SW1116 cell line, to
      determine the relationship between tumor stem cells and tumor biological
      behavior. We isolated populations of colon CSCs with the CD133+/CD44+ and CD133
      /CD44- surface phenotype from a human SW1116 colon adenocarcinoma cell line using
      flow cytometry. The expression of miRNA and mRNA of both sets of cells was
      examined with miRNA and mRNA arrays. Bioinformatic methods were used to analyze
      microarray results. We completed gene ontology analysis, pathway analysis, miRNA
      target gene prediction with databases. We identified a colon stem cell miRNA
      expression profile comprising 31 upregulated and 31 downregulated miRNAs, such as
      miR29a, miR29b, miR449b and miR4524. Some of these differentially expressed
      miRNAs may be involved in the regulation of stem cell differentiation. Gene
      ontology and pathway analyses showed that the differences are closely related to
      the function of the cell cycle, cell differentiation, signaling pathway,
      cytoskeletal proteins and cell-matrix adhesion in colon cancer stem cells. We
      found that miRNAs play an important role in regulating the expression of colon
      CSC characteristics. By regulating the expression of CSC signaling pathways,
      cytoskeleton and membrane proteins, miRNAs give tumor stem cells the
      macrobiological behavior of recurrence and metastasis. This study provides a new
      perspective on CRC metastasis and recurrence.

PMID- 23007738
TI  - A stage-wise approach for the analysis of multi-environment trials.
AB  - Plant breeders and variety testing agencies routinely test candidate genotypes
      (crop varieties, lines, test hybrids) in multiple environments. Such multi
      environment trials can be efficiently analysed by mixed models. A single-stage
      analysis models the entire observed data at the level of individual plots. This
      kind of analysis is usually considered as the gold standard. In practice,
      however, it is more convenient to use a two-stage approach, in which experiments
      are first analysed per environment, yielding adjusted means per genotype, which
      are then summarised across environments in the second stage. Stage-wise
      approaches suggested so far are approximate in that they cannot fully reproduce a
      single-stage analysis, except in very simple cases, because the variance
      covariance matrix of adjusted means from individual environments needs to be
      approximated by a diagonal matrix. This paper proposes a fully efficient stage
      wise method, which carries forward the full variance-covariance matrix of
      adjusted means from the individual environments to the analysis across the series
      of trials. Provided the variance components are known, this method can fully
      reproduce the results of a single-stage analysis. Computations are made efficient
      by a diagonalisation of the residual variance-covariance matrix, which
      necessitates a corresponding linear transformation of both the first-stage
      estimates (e.g. adjusted means and regression slopes for plot covariates) and the
      corresponding design matrices for fixed and random effects. We also exemplify the
      extension of the general approach to a three-stage analysis. The method is
      illustrated using two datasets, one real and the other simulated. The proposed
      approach has close connections with meta-analysis, where environments correspond
      to centres and genotypes to medical treatments. We therefore compare our
      theoretical results with recently published results from a meta-analysis.

PMID- 23007739
TI  - Enumeration of major peripheral blood leukocyte populations for multicenter
      clinical trials using a whole blood phenotyping assay.
AB  - Cryopreservation of peripheral blood leukocytes is widely used to preserve cells
      for immune response evaluations in clinical trials and offers many advantages for
      ease and standardization of immunological assessments, but detrimental effects of
      this process have been observed on some cell subsets, such as granulocytes, B
      cells, and dendritic cells. Assaying fresh leukocytes gives a more accurate
      picture of the in vivo state of the cells, but is often difficult to perform in
      the context of large clinical trials. Fresh cell assays are dependent upon
      volunteer commitments and timeframes and, if time-consuming, their application
      can be impractical due to the working hours required of laboratory personnel. In
      addition, when trials are conducted at multiple centers, laboratories with the
      resources and training necessary to perform the assays may not be located in
      sufficient proximity to clinical sites. To address these issues, we have
      developed an 11-color antibody staining panel that can be used with Trucount
      tubes (Becton Dickinson; San Jose, CA) to phenotype and enumerate the major
      leukocyte populations within the peripheral blood, yielding more robust cell-type
      specific information than assays such as a complete blood count (CBC) or assays
      with commercially-available panels designed for Trucount tubes that stain for
      only a few cell types. The staining procedure is simple, requires only 100 MUl of
      fresh whole blood, and takes approximately 45 minutes, making it feasible for
      standard blood-processing labs to perform. It is adapted from the BD Trucount
      tube technical data sheet (version 8/2010). The staining antibody cocktail can be
      prepared in advance in bulk at a central assay laboratory and shipped to the site
      processing labs. Stained tubes can be fixed and frozen for shipment to the
      central assay laboratory for multicolor flow cytometry analysis. The data
      generated from this staining panel can be used to track changes in leukocyte
      concentrations over time in relation to intervention and could easily be further
      developed to assess activation states of specific cell types of interest. In this
      report, we demonstrate the procedure used by blood-processing lab technicians to
      perform staining on fresh whole blood and the steps to analyze these stained
      samples at a central assay laboratory supporting a multicenter clinical trial.
      The video details the procedure as it is performed in the context of a clinical
      trial blood draw in the HIV Vaccine Trials Network (HVTN).

PMID- 23007740
TI  - Emerging optical and nuclear medicine imaging methods in rheumatoid arthritis.
AB  - Molecular and multimodal imaging procedures that complement the use of existing
      anatomical modalities for the diagnosis and monitoring of rheumatoid arthritis
      (RA) have undergone substantial developmental advances. These techniques have the
      potential to greatly improve the management of patients with RA through early
      diagnosis and maximization of the newly available opportunities for early
      therapeutic intervention. Quantitative, noninvasive monitoring of biomarkers of
      the molecular events induced during the onset of RA could be used to guide the
      initial selection of therapy and for assessment of early therapeutic responses.
      Biomolecular imaging techniques that can reveal the pathophysiological features
      of RA--including infrared thermography, near-infrared molecular imaging, and PET-
      are being used to investigate the earliest cellular and biochemical inflammatory
      events in the development of the disease. Noninvasive imaging of abnormal
      specific molecular events in early RA could enable early targeted intervention
      that could be tailored to optimize patient responses before destructive
      anatomical changes occur. In this Review, we summarize new advances in
      biomolecular imaging techniques, with an emphasis on their current state of
      development in terms of the management of RA.

PMID- 23007741
TI  - Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment.
AB  - Bone erosion is a central feature of rheumatoid arthritis and is associated with
      disease severity and poor functional outcome. Erosion of periarticular cortical
      bone, the typical feature observed on plain radiographs in patients with
      rheumatoid arthritis, results from excessive local bone resorption and inadequate
      bone formation. The main triggers of articular bone erosion are synovitis,
      including the production of proinflammatory cytokines and receptor activator of
      nuclear factor kappaB ligand (RANKL), as well as antibodies directed against
      citrullinated proteins. Indeed, both cytokines and autoantibodies stimulate the
      differentiation of bone-resorbing osteoclasts, thereby stimulating local bone
      resorption. Although current antirheumatic therapy inhibits both bone erosion and
      inflammation, repair of existing bone lesions, albeit physiologically feasible,
      occurs rarely. Lack of repair is due, at least in part, to active suppression of
      bone formation by proinflammatory cytokines. This Review summarizes the
      substantial progress that has been made in understanding the pathophysiology of
      bone erosions and discusses the improvements in the diagnosis, monitoring and
      treatment of such lesions.

PMID- 23007743
TI  - Rheumatoid arthritis: Obesity impairs efficacy of anti-TNF therapy in patients
      with RA.

PMID- 23007744
TI  - Therapy: Response to T-cell-dependent vaccine thwarted by TNF blockade.

PMID- 23007742
TI  - Differential diagnosis and management of Behcet syndrome.
AB  - Behcet syndrome (also known as Behcet disease) is a rare condition that is
      associated with considerable morbidity. Cases of Behcet syndrome have been
      reported worldwide, but the highest prevalence occurs in countries that border
      the ancient Silk Route, such as Turkey and Iran. Although oral ulceration,
      genital ulceration and eye disease are the classic triad of manifestations, the
      cardiovascular, gastrointestinal, musculoskeletal and central nervous systems can
      also be affected. The syndrome is chronic and relapsing with some patients having
      benign episodes whereas others have more serious complications, including
      blindness or the rupture of a pulmonary arterial aneurysm. Diagnosing Behcet
      syndrome, particularly outside of endemic regions, often incurs a considerable
      delay owing to the rarity of this condition. Furthermore, a paucity exists of
      data from randomized controlled trials on the optimal therapeutic approaches to
      use in patients, as well as a lack of informative laboratory surrogate markers to
      monitor disease progression. This Review discusses the issues surrounding the
      diagnosis and differential diagnosis of Behcet syndrome and presents the current
      approaches to managing patients with this complex group of disorders.

PMID- 23007745
TI  - Implementation of a cost-effective HPLC/UV approach for routine medical
      quantification of memantine in human serum.
AB  - BACKGROUND: In the near future, there will be no innovative drug principle for
      the treatment of dementia. Therefore, optimizing the efficacy of a drug is at
      present the most promising way to exploit its full pharmacological potential.
      METHOD: A high performance liquid chromatography with ultraviolet assay for
      memantine in serum from demented patients has been developed and validated. The
      analytical procedure involves offline solid phase extraction cartridges. Because
      memantine molecules lack chromophoric pi-electrons, a derivatization with dansyl
      chloride was required for detection by ultraviolet (UV) photometry. Analyses were
      performed on a Dionex high-performance liquid chromatography system with a
      Phenomenex Luna Phenyl-Hexyl analytical column and 0.02 mol/L potassium
      dihydrogen phosphate buffer/acetonitrile (40/60 V/V) as mobile phase at a flow
      rate of 0.4 mL/min. Dansylated memantine was detected at 218 nm; 2 more
      ultraviolet wavelengths at 254 nm and 336 nm were used as an overlay-control
      check. RESULTS: The retention time for dansylated memantine was 17.1 +/- 0.2
      minutes. The calibration curve was linear over a concentration range from 5 to
      160 ng/mL (n = 8/r2 > 0.999). The method had an accuracy of >90%. Intra-assay and
      inter-assay coefficients of variation were <5% and <13%, respectively, at 3
      different concentrations. The limit of quantification and the limit of detection
      were 2.9 ng/mL and 0.8 ng/mL, respectively. Among 100 substances prescribed as
      comedications in the treatment of dementia only fluvoxamine and zuclopenthixole
      showed retention times close to dansylated memantine (17.8 minutes and 18.1
      minutes, respectively). However, these 2 drugs were removed from patients'
      specimens during solid-phase extraction sample preparation. CONCLUSIONS: The
      method is applicable under conditions of daily routine as has been demonstrated
      by application of the method to patient serum samples. The quantification of 29
      samples showed that memantine concentrations suggested as "therapeutic" in the
      literature may only be reached by high doses of memantine.

PMID- 23007746
TI  - Limits to intensified mycophenolate mofetil dosing in kidney transplantation.
AB  - BACKGROUND: Studies have shown that achieving adequate exposure of mycophenolic
      acid (MPA) early post transplant is associated with less acute rejection in
      kidney recipients. Intensified dosing with the equivalent of mycophenolate
      mofetil (MMF) 3 g daily in tacrolimus-treated patients has been shown to increase
      exposure however about 15% remain below the lower therapeutic threshold of MPA
      area under the curve (AUC) of 30 mg . hr-1 . L-1 early post transplant. A post
      hoc analysis of this study showed that a target MPA AUC >40 mg . hr-1 . L-1 was
      most effective. The primary objective of this study was to determine whether 4 g
      daily of MMF would result in a greater proportion achieving adequate MPA
      exposure. MATERIALS AND METHODS: MMF 4 g daily was used in tacrolimus treated de
      novo kidney transplant recipients. A 3-point limited sample strategy was used to
      measure MPA AUC on days 5 and 14. Doses were adjusted at day 5 if exposure was
      high. RESULTS: In 30 patients, the mean AUC was 63 +/- 28 mg . hr-1 . L-1 on day
      5, with 13% (4/30) <= 30 mg . hr-1 . L-1 and 57% (17/30) >60 mg . hr-1 . L-1. The
      target MPA AUC was <40 mg . hr-1 . L-1 in 23% (7/30). Three patients developed
      gastrointestinal toxicity and required dose changes. Acute rejection occurred in
      only 2 patients (grade 1A and 2B) within 3 months (day 5 MPA AUCs were 29.9 and
      33 mg . hr-1 . L-1. On day 14 the mean AUC was 46 +/- 17 mg . hr-1 . L-1. Many
      were on MMF doses >2 g daily (8 on 3 g and 9 on 4 g daily). CONCLUSION: Compared
      to MMF 3 g daily, 4 g daily dose not result in a greater proportion adequately
      exposed. Rejections were few and occurred in the lower MPA exposed recipients.
      More than 50% of patients needed doses of MMF >2 g daily for 2 weeks to avoid
      underexposure. If intensified MPA dosing is considered, exceeding 3 g daily in
      tacrolimus-treated patients provides no added benefit.

PMID- 23007749
TI  - Introduction to the IEEE International Symposium on Applications of
      Ferroelectrics and International Symposium on Piezoresponse Force Microscopy and
      Nanoscale Phenomena in Polar Materials.
AB  - The 20th IEEE International Symposium on Applications of Ferroelectrics (ISAF)
      was held on July 24-27, 2011, in Vancouver, British Columbia, Canada, jointly
      with the International Symposium on Piezoresponse Force Microscopy and Nanoscale
      Phenomena in Polar Materials (PFM). Over a period of four days, approximately 400
      scientists, engineers, and students from around the world presented their work
      and discussed the latest developments in the field of ferroelectrics, related
      materials, and their applications. It is particularly encouraging to see that a
      large number of students (115) were attracted to the joint conference and
      presented high-quality research works. This trend is not only important to this
      conference series, but more importantly, it is vital to the future of the
      ferroelectrics field.

PMID- 23007750
TI  - Lead-free (Bi0.5Na0.5)TiO3-based thin films by the pulsed laser deposition
      process.
AB  - We have studied the effect of deposition parameters on the microstructure,
      crystallinity, and ferroelectric properties of 0.88(Bi(0.5)Na(0.5))TiO(3)
      0.08(Bi(0.5)K(0.5))TiO(3)?0.04BaTiO(3) thin films grown on SrRuO(3)-coated
      SrTiO(3) substrates by pulsed laser deposition. The parameters studied were the
      repetition rates, substrate temperatures, oxygen pressures, and laser energies.
      It was realized that the films prepared at 800 degrees C, 10 Hz, 400 mtorr, and
      1.2 Jcm(-2) exhibited the highest ferroelectric properties. The measured remanent
      polarization, dielectric constant at 1 kHz, and coercive field for this film were
      about 30 MUCcm(-2), 645, and 85 kVcm(-1), respectively. Increasing the oxygen
      pressure during deposition from 200 to 400 mtorr improved the crystallinity,
      microstructure, dielectric constant, and polarization of the films. The leakage
      current and dielectric loss were suppressed at 400 mtorr because of the lower
      concentration of oxygen vacancies and disappearing pinholes and surface
      undulations in the film deposited at this pressure.

PMID- 23007751
TI  - Shape-controlled crystal growth of Sr3NbGa3Si2O14 and Sr3TaGa3Si2O14
      piezoelectric crystals by the micro-pulling-down method.
AB  - We grew column-shaped Sr(3)NbGa(3)Si(2)O(14) (SNGS) and Sr(3)TaGa(3)Si(2)O(14)
      (STGS) langasite-type piezoelectric single crystals by the micro-pulling-down (MU
      PD) method. 3-mm-diameter SNGS and STGS crystals were grown using a Pt-Rh
      crucible with a 3-mm-diameter columnar die. According to X-ray rocking curve
      measurements, the grown crystals had crystallinity equivalent to that of crystals
      grown by the Czochralski (Cz) method. The crystals were single-phase materials
      with langasite-type crystal structure. The lattice parameters of the grown
      crystals were almost consistent with those of crystals grown by the Cz method.

PMID- 23007747
TI  - Pharmacokinetics of tacrolimus during pregnancy.
AB  - BACKGROUND: Information on the pharmacokinetics of tacrolimus during pregnancy is
      limited to case reports despite the increasing number of pregnant women being
      prescribed tacrolimus for immunosuppression. METHODS: Blood, plasma, and urine
      samples were collected over 1 steady-state dosing interval from women treated
      with oral tacrolimus during early to late pregnancy (n = 10) and postpartum (n =
      5). Total and unbound tacrolimus as well as metabolite concentrations in blood
      and plasma were assayed by a validated liquid chromatography/mass
      spectrometry/mass spectrometry (LC/MS/MS) method. A mixed-effect linear model was
      used for comparison across gestational age and using postpartum as the reference
      group. RESULTS: The mean oral clearance (CL/F) based on whole-blood tacrolimus
      concentration was 39% higher during mid-pregnancy and late pregnancy compared
      with postpartum (47.4 +/- 12.6 vs. 34.2 +/- 14.8 L/h, P < 0.03). Tacrolimus-free
      fraction increased by 91% in plasma (f(P)) and by 100% in blood (f(B)) during
      pregnancy (P = 0.0007 and 0.002, respectively). Increased fP was inversely
      associated with serum albumin concentration (r = -0.7, P = 0.003), which
      decreased by 27% during pregnancy. Pregnancy-related changes in f(P) and f(B)
      contributed significantly to the observed gestational increase in tacrolimus
      whole-blood CL/F (r2 = 0.36 and 0.47, respectively, P < 0.01). In addition,
      tacrolimus whole-blood CL/F was inversely correlated with both hematocrit and red
      blood cell counts, suggesting that binding of tacrolimus to erythrocytes
      restricts its availability for metabolism. Treating physicians increased
      tacrolimus dosages in study participants during pregnancy by an average of 45% to
      maintain tacrolimus whole-blood trough concentrations in the therapeutic range.
      This led to striking increases in unbound tacrolimus trough concentrations and
      unbound area under the concentration-time curve, by 112% and 173%, respectively,
      during pregnancy (P = 0.02 and 0.03, respectively). CONCLUSIONS: Tacrolimus
      pharmacokinetics are altered during pregnancy. Dose adjustment to maintain whole
      blood tacrolimus concentration in the usual therapeutic range during pregnancy
      increases circulating free drug concentrations, which may impact clinical
      outcomes.

PMID- 23007752
TI  - Shaped crystal growth of langasite-type piezoelectric single crystals and their
      physical properties.
AB  - We have grown shape-controlled langasite-type crystals by the micro-pulling-down
      (MU-PD) method. Columnar shaped La(3)Ta(0.5)Ga(5.5)O(14) (LTG),
      Ca(3)NbGa(3)Si(2)O(14) (CNGS), Ca(3)TaGa(3)Si(2)O(14) (CTGS),
      Sr(3)NbGa(3)Si(2)O(14) (SNGS), and Sr(3)Ta- Ga(3)Si(2)O(14) (STGS) crystals were
      grown using a Pt-Rh crucible with a 3-mm-diameter columnar die at the bottom. All
      grown crystals showed high transparency except for the peripheral area and
      diameter of approximately 3 mm. The chemical phases at the central parts of the
      grown crystals were identified as a single phase of langasite-type structure and
      their lattice parameters were almost the same as those of crystals grown by the
      Czochralski (Cz) method; however, some impurity phases were observed in the
      peripheral area. In X-ray rocking curve measurements, the grown crystals
      indicated equivalent crystallinity to the crystal grown by the Cz method. The
      piezoelectric constant d(11) of the CNGS crystal was 3.98 pC/N; this value is
      well correlated with those of previous reports.

PMID- 23007754
TI  - Coexistence of ferroelectric and relaxor states in Ba2PrxNd1-xFeNb4O15.
AB  - We have investigated the dielectric response of Ba(2)Pr(x)Nd(1-x)FeNb(4)O(15)
      ceramics (x = 0, 0.2, 0.5, 0.6, 0.8, 1) in the frequency range from 20 Hz to 1
      GHz. The obtained results confirmed the continuous transformation from the
      ferroelectric behavior of Ba2NdFeNb4O15 to the pure relaxor response of
      Ba(2)PrFeNb(4)O(15) with increasing x. For intermediate x values, coexisting
      ferroelectric transition and relaxor dielectric signatures were observed,
      corresponding to two different phenomena in the framework of these materials.
      Increasing the amount of Pr decreases the ferroelectric phase transition
      temperatures in these ceramics; a large cooling?heating hysteresis exceeding 50K
      was also observed.

PMID- 23007753
TI  - Dielectric and Mossbauer studies of ferroelectric and magnetic phase transitions
      in A-site and B-site substituted multiferroic PbFe0.5Nb0.5O3.
AB  - In the present study, we diluted either A- or B- sublattice of perovskite
      multiferroic PbFe(0.5)Nb(0.5)O(3) (PFN) and studied the changes of the magnetic
      and ferroelectric phase transition temperatures and dielectric properties caused
      by such dilution. Dielectric studies of PFN single crystals show that, in
      contrast to the commonly adopted view, the ferroelectric phase transition in PFN
      is non-diffused and the relaxor-like behavior usually observed in ceramic samples
      has an extrinsic nature. A-site substitutions (Ba, Ca) lead to the smearing of
      the permittivity-temperature maximum, lowering its maximum temperature, T(m) and
      inducing relaxor behavior. B-site diluting of PFN by Ti increases T(m) and only
      slightly affects the permittivity maximum diffuseness. Both A-site and B-site
      substitutions in PFN lead to lowering of its Neel temperature, T(N). However,
      above a certain compositional threshold, fast lowering of T(N) stops and a new
      magnetic state with comparatively high (~50K) transition temperature becomes
      stable in a rather wide compositional range.

PMID- 23007755
TI  - Impedance spectroscopy of PZT ceramics--measuring diffusion coefficients, mixed
      conduction, and Pb loss.
AB  - Sintering of lead zirconate titanate (PZT) at high temperatures results in loss
      of Pb unless an ambient Pb activity is maintained. The tell-tale sign of Pb loss
      is an increased conductivity, usually manifested in unacceptably high values of
      tandelta. The conductivity is caused by oxygen vacancies and/or electron holes
      which are a byproduct of Pb evaporation. In the first part of this paper, it is
      shown how impedance spectroscopy can be used to separate ionic and electronic
      conductivity in a properly designed sample by selection of appropriate boundary
      conditions. Subsequently, impedance is used to probe defect concentrations in PZT
      during prolonged annealing at 700 degrees C. It is found that oxygen vacancies
      are generated during annealing in air but the rate of generation actually
      decreases upon lowering the ambient pO(2). These results are explained by a model
      of Pb evaporation which, in this case, leads predominantly to oxygen vacancy
      generation. In principle, this effect could be used to generate a specific
      vacancy concentration in similar Pb-based oxides.

PMID- 23007756
TI  - A new SrBi4Ti4O15/CaBi4Ti4O15 thin-film capacitor for excellent electric
      stability.
AB  - SrBi(4)Ti(4)O(15) (SBTi) and CaBi(4)Ti(4)O(15) (CBTi) dielectric films of bismuth
      layered-structure dielectrics (BLSD) are prepared on Pt(100) film for
      constructing stacked-type dielectric capacitors; it is observed that they are c
      axis singleoriented crystalline films. Compared with the perovskite barium
      titanate family of (Ba,Sr)TiO(3) (BST), it is observed that the SBTi film keeps a
      low leakage of 10(-7) A/cm(2) at 250 kV/ cm, which is smaller by an order of
      magnitude than the BST film, even with thinner SBTi film. The temperature
      coefficient of capacitance (TCC) of the SBTi or CBTi film is about 100 to 250
      ppm/K and is much smaller than that of the perovskite BST film. Because the SBTi
      and CBTi films have opposite polarities of TCC in this experiment, they are
      expected to cancel out the temperature dependence in the SBTi/CBTi composite
      capacitor. These results indicate that the BLSD films of SBTi and CBTi are
      effective for application in high-temperature and high-permittivity capacitors
      with the practical barium perovskite oxide family.

PMID- 23007757
TI  - Temperature-stable high-energy-density capacitors using complex perovskite thin
      films.
AB  - Chemical-solution-derived thin film synthesis and dielectric characterizations of
      (1 - x)BaTiO(3-x)Bi(Mg,Ti) O(3) complex perovskites with compositions x <0.15
      have been explored for temperature-stable high-energy-density capacitor
      applications. Solution chemistry has been optimized to synthesize and stabilize
      the precursor solution. Solution-derived (1 - x)BaTiO(3-x)Bi(Mg,Ti)O(3) thin film
      samples in thicknesses ranging from 250 to 500 nm were fabricated by repeated
      spinning and subsequent crystallization processes. These thin films showed nearly
      linear polarization response with high relative dielectric permittivity exceeding
      900, which is beneficial for high-capacitance-density and high-energy-density
      capacitors. Average dielectric breakdown strengths of the dense films were as
      high as 2.08 MV/cm. The BaTiO(3)-Bi(Mg,Ti) O3 samples showed very low leakage
      current densities of the order of 10-8 A/cm(2) even at temperatures of 200
      degrees C. Based on the structural stability at high temperatures of the
      pseudocubic perovskite, the high dielectric permittivity and the typical P-E
      behaviors of the BaTiO(3)-Bi(Mg,Ti)O(3) thin films were also maintained at such
      high temperatures. Resulting energy density of the 500-nm-thick 0.88BaTiO(3)
      0.12Bi(Mg,Ti) O(3) thin film was as high as 37 J/cm(3) at 1.9 MV/cm. The high
      energy density and excellent temperature stability of the Ba- TiO(3)
      Bi(Mg,Ti)O(3) complex perovskite show promise for use in high-temperature pulse
      power capacitor applications.

PMID- 23007758
TI  - Nanodomain structures with hierarchical inhomogeneities in PMN-PT.
AB  - The nanometric domain configuration of (1 - x) Pb(Mg(1/3)Nb(2/3))O(3-x)PbTiO(3)
      [(1 - x)PMN-xPT] single crystals in the monoclinic phase around a morphotropic
      phase boundary (MPB) has been examined thoroughly by means of transmission
      electron microscopy (TEM). Domain structures with hierarchically inhomogeneous
      configuration were found in the monoclinic phase near the MPB region around x ~
      0.32, which are characterized as nanoscaled lamella-type domain structures with
      ~10 nm width inside macroscopic-sized banded domains with 100 to 200 nm width. To
      elucidate formation processes of the domain structures with hierarchically
      inhomogeneous configuration, an in situ TEM observation of changes of the domain
      structures in the temperature window between 298K and 500K was carried out. It is
      revealed that these nanoscaled lamella-type domain structures with ~10 nm width
      appear inside the banded domains as a result of the tetragonal structure and are
      inherent to the monoclinic phase.

PMID- 23007759
TI  - Ferroelectric switching in Bi4Ti3O12 nanorods.
AB  - We report the piezoelectric and ferroelectric properties of individual one
      dimensional objects made of Bi(4)Ti(3)O(12) (BiT). The nanorods and nanowires
      investigated in this study were fabricated by a two-step process: 1) preparation
      of reactive templates using hydrothermal-like synthesis and colloidal chemistry
      and 2) transformation of the reactive templates in Bi(4)Ti(3)O(12) by solid-state
      reaction, overcoming the morphological instability problem of 1-D templates.
      Using piezoresponse force microscopy (PFM) with both out-of-plane and in-plane
      detection capability, we show that both types of objects exhibit strong
      piezoelectric activity and good switching ferroelectric behavior. Analysis of the
      PFM hysteresis loops obtained revealed that the coercive voltage of the in-plane
      PFM signal can be either equal to or different from that of the out-of-plane
      response. We associate these situations with two types of polarization switching
      mechanisms: direct 180 degrees  switching, and via rotation of polarization,
      resulting from the independent switching of the components along the a- and
      ccrystallographic axes. In a few instances, we observe a negative piezoelectric
      coefficient, which we explain by the specific shape of the piezoelectric surface
      of Bi(4)Ti(3)O(12).

PMID- 23007760
TI  - Microstructural evolution and electrical properties of base-metal electroded
      BaTi4O9 materials with B-Si-Ba-Zn-O glass system.
AB  - Barium titanate-based microwave dielectrics usually require relatively high
      temperatures to sinter, which prevents the use of base metals such as copper for
      electrodes. In this work, BaTi(4)O(9) microwave dielectric ceramics co-fired with
      copper electrodes are made possible by adding B-Si-Ba- Zn-O glass to induce
      liquid-phase sintering at sufficiently low temperature and in reduced atmosphere.
      The microstructures and electric properties of the BaTi(4)O(9) ceramics thus
      obtained are carefully examined and studied. Proper glass composition may
      significantly facilitate mass transportation in the low-temperature co-fired
      ceramic (LTCC) material, resulting in better densification without serious
      degradation of electric properties. Although the B2O3/SiO2 ratio enhances the
      glass mobility during sintering, the BaO/ZnO ratio contributes to the chemical
      affinity of glass to BaTi(4)O(9) ceramics. In addition, various Ba-Ti-O phases
      with different Ba/Ti ratios may be found in the specimen through the X-ray
      diffraction patterns when the BaO/ZnO ratio is varied. If the BaO/ZnO ratio is
      high and the glass flows easily in the material, the Ba(4)Ti(13)O(30) phase is
      formed. If the BaO/ZnO ratio is low and the glass flows easily in the material,
      the BaTi(6)O(13) phase appears. We find that glass-induced Ba(4)Ti(13)O(30)
      transformation may significantly decrease Qxf values in the BT4-BSBZ materials.
      Therefore, the appropriate glass composition must be selected to ensure the phase
      stability of dielectrics to achieve the best performance possible.

PMID- 23007761
TI  - Domain structures and dielectric properties resulting from tweed precursors of
      relaxor ferroelectric solid-solution single-crystal 24Pb(In1/2Nb1/2)O3-46Pb
      (Mg1/3Nb2/3)O3-30PbTio3.
AB  - The domain structures of poled and depoled lead-based relaxor ferroelectric solid
      solution single-crystal 24Pb(In(1/2)Nb(1/2))O(3)-46Pb (Mg(1/3)Nb(2/3))O(3)
      30PbTio(3) are studied by polarized light microscopy, piezoresponse force
      microscopy (PFM), scanning electron microscopy (SEM), and dielectric
      spectroscopy. The domain structures in the nonergodic relaxor state are found by
      PFM to consist of tweed structures resulting from random fields from the
      competition between ferroelectric and antiferroelectric distortion, and planar
      defects found by SEM are treated as dislocations associated with strain
      accommodation, resulting in superior piezoelectric properties. This domain
      structure is found to be connected with hierarchical domain structures.

PMID- 23007762
TI  - Ferroelectric phase transition in LiNbO3: Insights from molecular dynamics.
AB  - Ab initio molecular dynamics within density functional theory is used for the
      first time to model the ferroelectric? paraelectric phase transition in LiNbO(3).
      Our calculations show that the structural phase transition is not an abrupt
      event, but rather a continuous process occurring over a range of about 100K and
      involving different ionic species at different temperatures. Because of the
      different behavior of the Li and Nb sublattices, the ferroelectric transition
      displays both displacive and order-disorder character.

PMID- 23007763
TI  - Linear and nonlinear optical response of LiNbO3 calculated from first principles.
AB  - The dielectric function and second-harmonic generation spectrum of ferroelectric
      LiNbO(3) are calculated from first principles. The calculations are based on the
      electronic structure obtained within density functional theory. The use of the GW
      approach to account for quasiparticle effects and the subsequent solution of the
      Bethe-Salpeter equation lead to a dielectric function in excellent agreement with
      measured data. The second harmonic generation spectrum calculated within the
      independent (quasi) particle approximation predicts strong nonlinear coefficients
      for photon energies above about 1.5 eV. The comparison with measured data
      suggests that the inclusion of self-energy effects in the nonlinear response
      improves the agreement with experiment.

PMID- 23007764
TI  - Formation of nanodomain structures during polarization reversal in congruent
      lithium niobate implanted with Ar ions.
AB  - We present the experimental study of the formation of self-similar nanodomain
      structures during polarization reversal in single-crystalline congruent lithium
      niobate (CLN) implanted by Ar ions. The formed dense surface nanodomain structure
      with charged domain walls differs drastically from the growth of the hexagonal
      domains in unimplanted CLN. The lack of wall shape stability during sideways
      domain wall motion was revealed. The analysis of the domain structure images in
      the bulk, obtained by Raman confocal microscopy, revealed the main stages of the
      domain structure evolution starting at unimplanted polar surface and consisting
      of nanodomain chain elongation, merging of isolated domains, and domain widening.
      The switching current data has been fitted by modification of Kolmogorov-Avrami
      formula for switching in a linearly increasing field. The observed experimental
      facts have been attributed to formation of an amorphous thin surface layer and
      increase of the bulk conductivity resulting from oxygen out-diffusion under
      radiation heating in vacuum during ion implantation. The formation of the
      experimentally obtained abnormal domain shapes has been explained while taking
      into account the step generation at the domain wall in the bulk during switching
      in a low electric field.

PMID- 23007765
TI  - Acoustic wave filter based on periodically poled lithium niobate.
AB  - Solutions for the development of compact RF passive transducers as an alternative
      to standard surface or bulk acoustic wave devices are receiving increasing
      interest. This article presents results on the development of an acoustic band
      pass filter based on periodically poled ferroelectric domains in lithium niobate.
      The fabrication of periodically poled transducers (PPTs) operating in the range
      of 20 to 650 MHz has been achieved on 3-in (76.2-mm) 500-MUm-thick wafers. This
      kind of transducer is able to excite elliptical as well as longitudinal modes,
      yielding phase velocities of about 3800 and 6500 ms(-1), respectively. A new type
      of acoustic band-pass filter is proposed, based on the use of PPTs instead of the
      SAWs excited by classical interdigital transducers. The design and the
      fabrication of such a filter are presented, as well as experimental measurements
      of its electrical response and transfer function. The feasibility of such a PPT
      based filter is thereby demonstrated and the limitations of this method are
      discussed.

PMID- 23007766
TI  - Evaluation of polarization of embedded piezoelectrics by the thermal wave method.
AB  - This work demonstrates the benefit of the thermal wave method for the evaluation
      of the polarization state of embedded piezoelectrics. Two types of samples were
      investigated: A low-temperature co-fired ceramics (LTCC)/lead zirconate titanate
      (PZT) sensor-actuator and a macro-fiber composite (MFC) actuator. At modulation
      frequencies below 10 Hz, the pyroelectric response was governed by thermal losses
      to the embedding layers. Here, the sample behavior was described by a
      harmonically heated piezoelectric plate exhibiting heat losses to the environment
      characterized by a single thermal relaxation time.

PMID- 23007767
TI  - Lead zirconate titanate nanoscale patterning by ultraviolet-based lithography
      lift-off technique for nano-electromechanical system applications.
AB  - The advantage of using lead zirconate titanate (PbZr(0.54)Ti(0.46)O(3)) ceramics
      as an active material in nanoelectromechanical systems (NEMS) comes from its
      relatively high piezoelectric coefficients. However, its integration within a
      technological process is limited by the difficulty of structuring this material
      with submicrometer resolution at the wafer scale. In this work, we develop a
      specific patterning method based on optical lithography coupled with a dual-layer
      resist process. The main objective is to obtain sub-micrometer features by
      lifting off a 100-nm-thick PZT layer while preserving the material's
      piezoelectric properties. A subsequent result of the developed method is the
      ability to stack several layers with a lateral resolution of few tens of
      nanometers, which is mandatory for the fabrication of NEMS with integrated
      actuation and read-out capabilities.

PMID- 23007768
TI  - Measurement of piezoelectric transformer vibrations by digital holography.
AB  - A method for the measurements of the out-of-plane displacement on the surface of
      vibrating object is presented herein. This method is based on frequency-shifted
      time-averaged digital holographic interferometry, employing the principle of
      phase shifting. This approach allows for significant noise reduction, which
      results in high sensitivity of measurements. This method makes it possible to
      measure vibrations with amplitudes in the nanometer range over the whole measured
      surface. This method was applied to the visualization of the out-of-plane
      vibration modes of piezoelectric transformers. The amplitude and modal shapes
      were measured with a very high resolution. Furthermore, aspects influencing the
      measurement errors are discussed and the measurement results by holographic
      method were compared with the well-established single-point laser interferometry
      measurement method.

PMID- 23007769
TI  - Design of low-loss 1-3 piezoelectric composites for high-power transducer
      applications.
AB  - Lead zirconate titanate (PZT)/polymer 1-3 composites have improved
      electromechanical properties compared with monolithic counterparts, but possess a
      low mechanical quality factor, limiting their use in high-power transducer
      applications. The goal of this work was to improve the mechanical quality factor
      of 1-3 PZT/polymer composites by optimizing the polymer materials. Theoretical
      analysis and modeling were performed for optimum composite design and various
      polymers were prepared and characterized. 1-3 piezocomposites were constructed
      and their electromechanical properties were experimentally determined. The
      results demonstrated that the composites with high-thermal-conductivity polymers
      generally have degraded electromechanical properties with significantly decreased
      mechanical quality factors, whereas the composites filled with low-loss and low
      moduli polymers were found to have higher mechanical quality factors with higher
      electromechanical coupling factors: Q(m) ~ 200 and k(t) ~ 0.68 for PZT4
      composites; Q(m) ~ 400 and k(t) ~ 0.6 for PZT8 composites. The improved
      mechanical quality factor of 1-3 piezocomposites may offer improved performance
      and thermal stability of transducers under high-drive operation.

PMID- 23007770
TI  - Non-planar pad-printed thick-film focused high-frequency ultrasonic transducers
      for imaging and therapeutic applications.
AB  - Pad-printed thick-film transducers have been shown to be an interesting
      alternative to lapped bulk piezoceramics, because the film is deposited with the
      required thickness, size, and geometry, thus avoiding any subsequent machining to
      achieve geometrical focusing. Their electromechanical properties are close to
      those of bulk ceramics with similar composition despite having a higher porosity.
      In this paper, padprinted high-frequency transducers based on a low-loss
      piezoceramic composition are designed and fabricated. High-porosity ceramic
      cylinders with a spherical top surface are used as the backing substrate. The
      transducers are characterized in view of imaging applications and their imaging
      capabilities are evaluated with phantoms containing spherical inclusions and in
      different biological tissues. In addition, the transducers are evaluated for
      their capability to produce high-acoustic intensities at frequencies around 20
      MHz. High-intensity measurements, obtained with a calibrated hydrophone, show
      that transducer performance is promising for applications that would require the
      same device to be used for imaging and for therapy. Nevertheless, the transducer
      design can be improved, and simulation studies are performed to find a better
      compromise between low-power and high-power performance. The size, geometry, and
      constitutive materials of optimized configurations are proposed and their
      feasibility is discussed.

PMID- 23007771
TI  - Application of single-crystalline PMN-PT and PIN-PMN-PT in high-performance
      pyroelectric detectors.
AB  - The suitability for use in pyroelectric detectors of single-crystalline doped and
      undoped lead indium niobate-lead magnesium niobate-lead titanate was tested and
      compared with high-quality Mn-doped lead magnesium niobate-lead titanate and
      standard lithium tantalate. Pyroelectric and dielectric measurements confirmed an
      increased processing and operating temperature range because of the higher phase
      transitions of lead indium niobate-lead magnesium niobate-lead titanate.
      Pyroelectric coefficients of 705 to 770 MUC/m(2)K were obtained with doped and
      undoped lead indium niobate-lead magnesium niobate-lead titanate, which are about
      70% to 80% of the pyroelectric coefficient of lead magnesium niobate-lead
      titanate but 4 times higher than standard lithium tantalate. Manganese doping has
      been proved as a solution to decrease the dielectric loss of lead magnesium
      niobate-lead titanate and it also works well for lead indium niobate-lead
      magnesium niobate-lead titanate. An outstanding specific detectivity D* of about
      1.1 . 10(9) cm.Hz(1/2)/W was achieved at a frequency of 2 Hz for Mn-doped lead
      magnesium niobate-based detectors.

PMID- 23007772
TI  - A piezoelectric active mirror suspension system embedded into low-temperature
      cofired ceramic.
AB  - Low-temperature cofired ceramic (LTCC) has proven to be a cost-effective,
      flexible technology for producing complicated structures such as sensors,
      actuators, and microsystems. This paper presents a piezoelectric active mirror
      suspension system embedded into LTCC. In the structure, the LTCC was used as a
      package, for the passive layers of piezoelectric monomorphs, as support for the
      mirrors, and as a substrate for the conductors. The active mirror structure, 17
      mm in diameter, was made by compiling 20 LTCC layers using common LTCC processing
      techniques. Each sample contained a laser-micromachined bulk lead zirconate
      titanate (PZT) structure which formed a monomorph with the LTCC during the firing
      process. A mirror substrate (diameter 4 mm) was mounted in the middle of the
      monomorph arms for evaluation of the positioning performance, where each of the
      three arms had independent signal electrodes and a common ground electrode.
      Electrical and electromechanical properties were investigated with an LCR meter,
      network analyzer, and laser vibrometer for the different arms and the mirror. The
      active mirror structure exhibited more than 1 MUm dc displacement for mirror
      leveling and also allowed small changes in mirror angle up to 0.06 degrees . The
      first bending resonance frequency of the structure with the mirror was detected
      at 11.31 kHz with 4.0 MUm displacement; 13.02 kHz and 2.7 MUm were obtained
      without the mirror. The structure exhibited characteristics feasible for further
      utilization in tunable Fabry-Perot filter applications, allowing the mounting of
      active mirrors on both sides with distance and angle control.

PMID- 23007773
TI  - Effect of manganese and vanadium valences on microstructures and reliability of
      BaTiO3-based multi-layer ceramic capacitors.
AB  - The valences of manganese and vanadium oxides in multi-layer ceramic capacitors
      (MLCCs), sintered under a reducing atmosphere, were investigated using electron
      paramagnetic resonance; insulation resistance degradation was analyzed using
      impedance spectroscopy in highly accelerated lifetime tests to clarify the
      influences of manganese and vanadium on both the electrical properties and
      microstructure of MLCCs. The Mn(2+) was stable in the reducing-atmospheresintered
      MLCCs and formed a grain boundary. Vanadium mitigated insulation resistance
      degradation and increased the reliability of the MLCCs. Although V4+ was detected
      in MLCCs that had 0.20 mol% and 0.30 mol% of added vanadium, the electrical
      properties were dependent upon other ions, e.g., V(3+) or V(5+). All vanadium
      ions except for V(4+) decreased the insulation resistance of ceramic/electrode
      interface. This is because vanadium reduces electric field concentration at the
      ceramic/ electrode interface and delays the onset of oxygen vacancy migration in
      the early stages of a highly accelerated lifetime test.

PMID- 23007774
TI  - Application of piezoelectric macro-fiber-composite actuators to the suppression
      of noise transmission through curved glass plates.
AB  - This paper analyzes the possibility of increasing the acoustic transmission loss
      of sound transmitted through planar or curved glass shells using attached
      piezoelectric macro fiber composite (MFC) actuators shunted by active circuits
      with a negative capacitance. The key features that control the sound transmission
      through the curved glass shells are analyzed using an analytical approximative
      model. A detailed analysis of the particular arrangement of MFC actuators on the
      glass shell is performed using a finite element method (FEM) model. The FEM model
      takes into account the effect of a flexible frame that clamps the glass shell at
      its edges. A method is presented for the active control of the Young's modulus
      and the bending stiffness coefficient of the composite sandwich structure that
      consists of a glass plate and the attached piezoelectric MFC actuator. The
      predictions of the acoustic transmission loss frequency dependencies obtained by
      the FEM model are compared with experimental data. The results indicate that it
      is possible to increase the acoustic transmission loss by 20 and 25 dB at the
      frequencies of the first and second resonant modes of the planar and curved glass
      shells, respectively, using the effect of the shunt circuit with a negative
      capacitance.

PMID- 23007775
TI  - Fabrication of an atrazine acoustic immunosensor based on a drop-deposition
      procedure.
AB  - Among the various novel analytical systems, immunosensors based on acoustic waves
      are of emerging interest because of their good sensitivity, real-time monitoring
      capability, and experimental simplicity. In this work, piezoelectric
      immunosensors were constructed for the detection of atrazine through the
      immobilization of specific monoclonal anti-atrazine antibodies on thiolated
      modified quartz crystal microbalances (QCMs). The immunoassay was conducted by a
      novel drop-deposition procedure using different atrazine dilutions in phosphate
      buffer solution ranging from 10(-10) to 10(-1) mg/mL. The immunoreactions between
      varying contents of atrazine and its antibody were dynamically exhibited through
      in situ monitoring of the frequency and motional resistance changes over 20 min.
      Thus, atrazine recognition by the anti-atrazine antibody leads to a decrease of
      the resonant frequency that is proportional to a given atrazine concentration.
      Interestingly, the motional resistance also increased proportionally during the
      measurements, which could be attributed to the specific viscoelastic properties
      and/or conformation changes of the antibodies once the immunoreactions occurred.
      By combining the measurements of frequency with those of motional resistance,
      additional information was provided about the interaction between the atrazine
      named antigen and its respective antibody. Finally, the analytical specificity of
      the immunosensor to atrazine was evaluated through the response to a nonspecific
      anti-human IgG antibody-modified QCM crystal under the same drop conditions.

PMID- 23007776
TI  - Vibration energy harvesting using a piezoelectric circular diaphragm array.
AB  - This paper presents a method for harvesting electric energy from mechanical
      vibration using a mechanically excited piezoelectric circular membrane array. The
      piezoelectric circular diaphragm array consists of four plates with series and
      parallel connection, and the electrical characteristics of the array are examined
      under dynamic conditions. With an optimal load resistor of 160 kOmega, an output
      power of 28 mW was generated from the array in series connection at 150 Hz under
      a prestress of 0.8 N and a vibration acceleration of 9.8 m/s(2), whereas a
      maximal output power of 27 mW can be obtained from the array in parallel
      connection through a resistive load of 11 kOmega under the same frequency,
      prestress, and acceleration conditions. The results show that using a
      piezoelectric circular diaphragm array can significantly increase the output of
      energy compared with the use of a single plate. By choosing an appropriate
      connection pattern (series or parallel connections) among the plates, the
      equivalent impedance of the energy harvesting devices can be tailored to meet the
      matched load of different applications for maximal power output.

PMID- 23007777
TI  - Improvement of low-frequency characteristics of piezoelectric speakers based on
      acoustic diaphragms.
AB  - The vibrational characteristics of 3 types of the acoustic diaphragms are
      investigated to enhance the output acoustic performance of the piezoelectric
      ceramic speaker in a low-frequency range. In other to achieve both a higher
      output sound pressure level and wider frequency range of the piezoelectric
      speaker, we have proposed a rubber/resin bi-layer acoustic diaphragm. The
      theoretical square-root dependence of the fundamental resonant frequency on the
      thickness and Young's modulus of the acoustic diaphragm was verified by finite
      element analysis simulation and laser scanning vibrometer measurement. The
      simulated resonant frequencies for each diaphragm correspond well to the measured
      results. From the simulated and measured resonant frequency results, it is found
      that the fundamental resonant frequency of the piezoelectric ceramic speaker can
      be designed by adjusting the thickness ratio of the rubber/resin bi-layer
      acoustic diaphragm. Compared with a commercial piezoelectric speaker, the
      fabricated piezoelectric ceramic speaker with the rubber/resin bi-layer diaphragm
      has at least 10 dB higher sound pressures in the low-frequency range of less than
      1 kHz.

PMID- 23007778
TI  - An L-section DC electric field switchable bulk acoustic wave solidly mounted
      resonator filter based on Ba0.5Sr0.5TiO3.
AB  - This paper reports on the modeling, fabrication, and experimental results of a
      voltage switchable barium strontium titanate solidly mounted resonator filter at
      6 GHz. The filter insertion loss was measured to be -4.26 dB and the return loss
      to be -13.5 dB. The 3-dB bandwidth was measured to be 72 MHz and the quality
      factor was calculated to be 83. The data were collected at a dc bias voltage of
      10 V. Temperature data were also collected, and the filter demonstrated a 0.71-dB
      increase in insertion loss and a 7-MHz decrease in center frequency with increase
      in temperature.

PMID- 23007779
TI  - Applications of piezoelectric materials in oilfield services.
AB  - Piezoelectric materials are used in many applications in the oilfield services
      industry. Four illustrative examples are given in this paper: marine seismic
      survey, precision pressure measurement, sonic logging-while-drilling, and
      ultrasonic bore-hole imaging. In marine seismics, piezoelectric hydrophones are
      deployed on a massive scale in a relatively benign environment. Hence, unit cost
      and device reliability are major considerations. The remaining three applications
      take place downhole in a characteristically harsh environment with high
      temperature and high pressure among other factors. The number of piezoelectric
      devices involved is generally small but otherwise highly valued. The selection of
      piezoelectric materials is limited, and the devices have to be engineered to
      withstand the operating conditions. With the global demand for energy increasing
      in the foreseeable future, the search for hydrocarbon resources is reaching into
      deeper and hotter wells. There is, therefore, a continuing and pressing need for
      high-temperature and high-coupling piezoelectric materials.

PMID- 23007780
TI  - High-data-rate ultrasonic through-metal communication.
AB  - A link-adaptive frequency division multiplexing (OFDM) ultrasonic physical layer
      is proposed for high-data-rate communications through metal walls. The ultrasonic
      link allows for communication without physical penetration of the metal barrier.
      Link-adaptive OFDM mitigates the severe frequency- selective fading of the
      ultrasonic channel and greatly improves throughput over impulse or narrowband
      communication systems. Throughput improvements of 300% are demonstrated over
      current narrowband low-frequency techniques, and show improved spectral
      efficiency over high-frequency techniques found in the literature.

PMID- 23007781
TI  - Compounding in synthetic aperture imaging.
AB  - A method for obtaining compound images using synthetic aperture data is
      investigated using a convex array transducer. The new approach allows spatial
      compounding to be performed for any number of angles without reducing the frame
      rate or temporal resolution. This important feature is an intrinsic property of
      how the compound images are constructed using synthetic aperture data and an
      improvement compared with how spatial compounding is obtained using conventional
      methods. The synthetic aperture compound images are created by exploiting the
      linearity of delay-and-sum beamformation for data collected from multiple
      spherical emissions to synthesize multiple transmit and receive apertures,
      corresponding to imaging the tissue from multiple directions. The many images are
      added incoherently, to produce a single compound image. Using a 192-element, 3.5
      MHz, lambda-pitch transducer, it is demonstrated from tissue-phantom measurements
      that the speckle is reduced and the contrast resolution improved when applying
      synthetic aperture compound imaging. At a depth of 4 cm, the size of the
      synthesized apertures is optimized for lesion detection based on the speckle
      information density. This is a performance measure for tissue contrast resolution
      which quantifies the tradeoff between resolution loss and speckle reduction. The
      speckle information density is improved by 25% when comparing synthetic aperture
      compounding to a similar setup for compounding using dynamic receive focusing.
      The cystic resolution and clutter levels are measured using a wire phantom setup
      and compared with conventional application of the array, as well as to synthetic
      aperture imaging without compounding. If the full aperture is used for synthetic
      aperture compounding, the cystic resolution is improved by 41% compared with
      conventional imaging, and is at least as good as what can be obtained using
      synthetic aperture imaging without compounding.

PMID- 23007782
TI  - Quantitative ultrasound estimates from populations of scatterers with continuous
      size distributions: effects of the size estimator algorithm.
AB  - Quantitative ultrasonic techniques using backscatter coefficients (BSCs) may fail
      to produce physically meaningful estimates of effective scatterer diameter (ESD)
      when the analysis media contains scatterers of different sizes. In this work,
      three different estimator algorithms were used to produce estimates of ESD. The
      performance of the three estimators was compared over different frequency bands
      using simulations and experiments with physical phantoms. All estimators produced
      ESD estimates by comparing the estimated BSCs with a scattering model based on
      the backscattering cross section of a single spherical fluid scatterer. The first
      estimator consisted of minimizing the average square deviation of the
      logarithmically compressed ratio between the estimated BSCs and the scattering
      model. The second and third estimators consisted of minimizing the mean square
      error between the estimated BSCs and a linear transformation of the scattering
      model with and without considering an intercept, respectively. Simulations were
      conducted over several analysis bandwidths between 1 and 40 MHz from populations
      of scatterers with either a uniform size distribution or a distribution based on
      the inverse cubic of the size. Diameters of the distributions ranged between [25,
      100], [25, 50], [50, 100], and [50, 75] MUm. Experimental results were obtained
      from two gelatin phantoms containing cross-linked dextran gel spheres ranging in
      diameter from 28 to 130 MUm and 70 to 130 MUm, respectively, and 5-, 7.5-, 10-,
      and 13-MHz focused transducers. Significant differences in the performances of
      the ESD estimator algorithms as a function of the analysis frequency were
      observed. Specifically, the third estimator exhibited potential to produce
      physically meaningful ESD estimates even for large ka values when using a single
      size scattering model if sufficient analysis bandwidth was available.

PMID- 23007783
TI  - Ultrasonic measurement of bone thickness for spinal surgery.
AB  - We measured the thickness of the transverse structures associated with the bovine
      coccygeal transverse processes (bone specimen) by using ultrasonic waves and
      examined the reliability of this measurement for use in spinal surgery. We first
      measured the velocity of ultrasonic waves propagating in the spinous process. We
      then made a hole in the transverse process with an air drill and placed an
      ultrasonic transducer with a center frequency of 10 MHz in the hole. The time of
      reflection of the ultrasonic wave from the underside of the transverse process
      was detected to estimate the remaining bone thickness. The thickness estimated by
      using ultrasound was compared with the thickness measured by microscopic
      examination. We could detect reflection waves from the underside of the
      transverse process in 91.7% of cases (i.e., 22 of 24 measurements using 6 bones
      from 3 cows). The thickness of the transverse processes in which we detected the
      waves varied from 0.24 to 6.8 mm. The 95% limit of agreement between ultrasonic
      and histological measurement was 0.71 mm. Pearson's correlation coefficient
      showed a strong and positive relationship between the two measurements (r = 0.97,
      n = 22, P <0.0001).

PMID- 23007784
TI  - Synergistic enhancements of ultrasound image contrast with a combination of phase
      aberration correction and dual apodization with cross-correlation.
AB  - Dual apodization with cross-correlation (DAX) is a novel adaptive beamforming
      technique which utilizes two distinct apodization functions in suppressing side
      lobes and clutter. Previous studies have shown that the performance of DAX in
      minimizing the effects of phase aberration diminishes with increasing aberrator
      strength. To achieve greater improvement in image contrast, we propose, in this
      paper, to combine DAX with a phase aberration correction algorithm based on
      nearest-neighbor cross-correlation (NNCC). Our simulation and experimental
      results presented in this work showed that the proposed method allows for
      synergistic enhancements of image contrast and achieves greater improvement in
      image quality than using DAX alone or phase aberration correction alone in the
      presence of weak and strong aberrators. Compared with standard delay-and-sum
      (DAS) beamforming, using the proposed method on simulated data with weak and
      strong aberrations increased the contrast-to-noise ratio (CNR) values from 4.10
      to 10.96 and from 1.69 to 9.80, respectively. Experimental results were obtained
      using pork tissues of 4 and 10 mm thickness and a tissue-mimicking phantom. The
      CNR values increased from 3.74 to 9.72 for the 4-mm pork aberrator and from 1.27
      to 8.17 for the 10-mm pork aberrator.

PMID- 23007785
TI  - An automatic compact Schlieren imaging system for ultrasound transducer testing.
AB  - The current standard used for the characterization of ultrasonic transducers is
      the hydrophonic technique, which is able to measure the acoustic pressure
      profile. This technique allows a quantitative analysis, but is marred by several
      problems. A scan of the region of interest is a time-consuming operation,
      especially when measuring a long acoustic beam. Furthermore, a hydrophone placed
      near the radiating surface is certainly an impediment to the free propagation of
      the field. Off-axis measurements can be inaccurate because of the angular
      response of the hydrophone. These problems, together with the costs, have
      encouraged the search for an alternative quick and inexpensive test system. The
      well-known Schlieren technique allows a real-time visualization of the whole
      pressure range of the transducers, but to display the entire beam emitted by the
      transducers it is necessary to use very large-diameter lenses, with focal lengths
      of several meters. Such systems are very cumbersome and difficult to use. The
      system developed in this paper allows the imaging of an acoustic beam up to 200
      mm in length, but the system is compact, being only about 1 m long and 0.30 m
      wide. A similar system based on the classic Schlieren effect would be several
      meters long, with lenses of 200 mm in diameter. Finally, the system can
      reconstruct the section of the beam at any height, using an acoustic tomography
      technique, and can also implement a quantitative analysis. Because it uses only
      commercial components, the developed and fabricated ultrasonic beam analyzer is a
      very low-cost imaging system. The goal of this work is to create a compact, low
      cost system based on this technique to test a wide range of ultrasonic
      transducers up to 40 MHz and above.

PMID- 23007786
TI  - Metglas/Pb(Mg1/3Nb2/3)O3-PbTiO3 magnetoelectric gradiometric sensor with high
      detection sensitivity.
AB  - We developed a novel biaxial magnetoelectric (ME) gradiometer sensor system using
      Metglas/ Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) laminates for investigation of ac
      magnetic dipole detection. We demonstrate a detection sensitivity of 20 pT/?Hz in
      an open environment (unshielded) at quasi-static frequencies with a noise
      rejection efficiency of 23.5 dB, relative to a uniform external noise. In
      addition, a signal processing method was used to compute the magnetic field
      amplitude at a driven frequency of 7 Hz, and the results were also verified by
      theory. Practical testing and mathematical predictions show that there are only
      7.2% and 4.2% gradiometric measurement errors in the x- and y-axis gradiometer
      components, enabling high-precision target detection.

PMID- 23007791
TI  - Minimizing side reactions in chemoenzymatic dynamic kinetic resolution:
      organometallic and material strategies.
AB  - Chemoenzymatic dynamic kinetic resolution (DKR) of rac-1-phenyl ethanol into R-1
      phenylethanol acetate was investigated with emphasis on the minimization of side
      reactions. The organometallic hydrogen transfer (racemization) catalyst was
      varied, and this was observed to alter the rate and extent of oxidation of the
      alcohol to form ketone side products. The performance of highly active catalyst
      [(pentamethylcyclopentadienyl)IrCl(2)(1-benzyl,3-methyl-imidazol-2-ylidene)] was
      found to depend on the batch of lipase B used. The interaction between the bio-
      and chemo-catalysts was reduced by employing physical entrapment of the enzyme in
      silica using a sol-gel process. The nature of the gelation method was found to be
      important, with an alkaline method preferred, as an acidic method was found to
      initiate a further side reaction, the acid catalyzed dehydration of the secondary
      alcohol. The acidic gel was found to be a heterogeneous solid acid.

PMID- 23007792
TI  - Interventions to improve psychological functioning and health outcomes of HIV
      infected individuals with a history of trauma or PTSD.
AB  - The experience of early or later life trauma in HIV-positive adults can have
      devastating mental and physical health consequences. Women bear the brunt of this
      double burden. Depression, posttraumatic stress disorder, and alcohol and drug
      use disorders are among the most common psychiatric disorders documented, both in
      infected women and men, in high-, middle-, and low-income countries. Traumatized
      individuals, particularly those with childhood sexual abuse characterized by
      repeated traumatization, are at high risk of engaging in risky behaviors,
      including substance abuse and sexual promiscuity. These issues are further
      compounded by stigma, discrimination, poverty, and low social support. While
      there is a significant need to pay more attention to psychiatric and
      psychological outcomes in the context of HIV-trauma and improve screening for
      traumatic stress in HIV care settings, there are currently few treatment and
      secondary prevention studies. Group cognitive-behavioral strategies, including
      prolonged exposure, coping skills training, and stress management have, to date,
      shown some evidence for efficacy in HIV-positive individuals with childhood
      trauma and in those with PTSD.

PMID- 23007793
TI  - The protein tyrosine phosphatase receptor type J is regulated by the pVHL-HIF
      axis in clear cell renal cell carcinoma.
AB  - Mass spectrometry analysis of renal cancer cell lines recently suggested that the
      protein-tyrosine phosphatase receptor type J (PTPRJ), an important regulator of
      tyrosine kinase receptors, is tightly linked to the von Hippel-Lindau protein
      (pVHL). Therefore, we aimed to characterize the biological relevance of PTPRJ for
      clear cell renal cell carcinoma (ccRCC). In pVHL-negative ccRCC cell lines, both
      RNA and protein expression levels of PTPRJ were lower than those in the
      corresponding pVHL reconstituted cells. Quantitative RT-PCR and western blot
      analysis of ccRCC with known VHL mutation status and normal matched tissues as
      well as RNA in situ hybridization on a tissue microarray (TMA) confirmed a
      decrease of PTPRJ expression in more than 80% of ccRCCs, but in only 12% of
      papillary RCCs. ccRCC patients with no or reduced PTPRJ mRNA expression had a
      less favourable outcome than those with a normal expression status (p = 0.05).
      Sequence analysis of 32 PTPRJ mRNA-negative ccRCC samples showed five known
      polymorphisms but no mutations, implying other mechanisms leading to PTPRJ's down
      regulation. Selective silencing of HIF-alpha by siRNA and reporter gene assays
      demonstrated that pVHL inactivation reduces PTPRJ expression through a HIF
      dependent mechanism, which is mainly driven by HIF-2alpha stabilization. Our
      results suggest PTPRJ as a member of a pVHL-controlled pathway whose suppression
      by HIF is critical for ccRCC development.

PMID- 23007794
TI  - Serum 25-hydroxyvitamin D, osteocalcin, and parathormone status in children with
      meningomyelocele.
AB  - Sufficient vitamin D levels are required for normal skeletal development and
      mineralization. This is particularly important in children with meningomyelocele
      who are at an increased risk of osteoporosis. The purpose of this study was to
      assess serum 25-hydroxyvitamin D [25(OH)D] and the biochemical markers of bone
      metabolism (parathormone, osteocalcin, alkaline phosphatase, and electrolytes) in
      children with meningomyelocele. The patient group comprised 33 children with
      meningomyelocele. The mean 25(OH)D was 11.51 +/- 7.87 ng/mL. A total of 97% of
      the subjects had a 25(OH)D level in the insufficient range (< 30 ng/mL) and 48.5%
      had a 25(OH)D level less than 10 ng/mL. Almost all patients had serum osteocalcin
      and phosphorus concentrations above the normal limits. The level of 25(OH)D
      negatively correlated with age and body weight. There were no correlations
      between the biochemical markers of bone metabolism and the ambulatory status. A
      significant correlation between serum 25(OH)D and osteoporosis was found.

PMID- 23007795
TI  - Treatment of refractory neonatal seizures with topiramate.
AB  - OBJECTIVE: The objective of this study is to describe the usefulness of
      topiramate in refractory neonatal seizures. RESULTS: We reported the clinical off
      label use of topiramate in three cases of refractory neonatal seizures of unclear
      origin with no response to conventional antiepileptic drugs. In all cases, the
      seizures were completely controlled with adding topiramate. All patients became
      seizure free during hospitalization and were followed by approximately 1 year
      after hospital discharge, with monotherapy with topiramate. COMMENTS: The
      clinical off-label use of topiramate in neonatal seizures is still incipient.
      When searching publications in this matter, only one report was identified.
      Because of its efficacy for both seizures and neuroprotection, topiramate could
      be a useful choice in refractory neonatal seizures.

PMID- 23007797
TI  - Determination of hydrazine hydrate based on electrochemiluminescence of
      Ru(bpy)3(2+).
AB  - Considering of the basic properties and also the two nitrogen atoms in the
      structure, hydrazine hydrate was employed to be an amine additive candidate, to
      build a Ru(bpy)(3)(2+) /hydrazine electrochemiluminescence (ECL) system, and ECL
      of Ru(bpy)(3)(2+) has been employed for the determination of hydrazine hydrate in
      the paper. The result demonstrated that the logarithmic ECL increasing (DeltaECL
      = ECL(after addition of hydrazine) - ECL(before addition of hydrazine)) versus
      the logarithmic concentration of hydrazine hydrate is linear over a concentration
      range of 1.0 * 10(-9) to 1.0 * 10(-5) mol/L, on both glassy carbon and Pt
      electrodes in a pH 9 phosphate buffer. The hydrazine hydrate detection limit was
      down to 1.0 * 10(-9) mol/L, comparatively lower than other detection methods. To
      check its applicability, the proposed method was applied to the determination of
      hydrazine hydrate added into a tap water sample with good reproducibility and
      stability. All these provide a possibility to develop a novel ECL detection
      method for hydrazine in water.

PMID- 23007798
TI  - Quantifying urban heat island intensity in Hong Kong SAR, China.
AB  - This paper addresses the methodological concerns in quantifying urban heat island
      (UHI) intensity in Hong Kong SAR, China. Although the urban heat island in Hong
      Kong has been widely investigated, there is no consensus on the most appropriate
      fixed point meteorological sites to be used to calculate heat island intensity.
      This study utilized the Local Climate Zones landscape classification system to
      classify 17 weather stations from the Hong Kong Observatory's extensive fixed
      point meteorological observation network. According to the classification
      results, the meteorological site located at the Hong Kong Observatory
      Headquarters is the representative urban weather station in Hong Kong, whereas
      sites located at Tsak Yue Wu and Ta Kwu Ling are appropriate rural or
      nonurbanized counterparts. These choices were validated and supported
      quantitatively through comparison of long-term annual and diurnal UHI intensities
      with rural stations used in previous studies. Results indicate that the rural
      stations used in previous studies are not representative, and thus, the past UHI
      intensities calculated for Hong Kong may have been underestimated.

PMID- 23007796
TI  - The relationship between tissue oxygenation and redox status using magnetic
      resonance imaging.
AB  - The recent development of a bi-modality magnetic resonance imaging/electron
      paramagnetic resonance imaging (MRI/EPRI) platform has enabled longitudinal
      monitoring of both tumor oxygenation and redox status in murine cancer models.
      The current study used this imaging platform to test the hypothesis that a more
      reducing tumor microenvironment accompanies the development of tumor hypoxia. To
      test this, the redox status of the tumor was measured using Tempol as a redox
      sensitive MRI contrast agent, and tumor hypoxia was measured with Oxo63, which is
      an oxygen-sensitive EPRI spin probe. Images were acquired every 1-2 days in mice
      bearing SCCVII tumors. The median pO(2) decreased from 14 mmHg at 7 days after
      tumor implantation to 7 mmHg at 15 days after implantation. Additionally, the
      hypoxic fraction, defined as the percentage of the tumor that exhibited a
      pO(2)<10 mmHg, increased with tumor size (from 10% at 500 mm(3) to 60% at 3,500
      mm(3)). The rate of Tempol reduction increased as a function of tumor volume (0.4
      min(-1) at 500 mm(3) to 1.7 min(-1) at 3,500 mm(3)), suggesting that the tumor
      microenvironment became more reduced as the tumor grew. The results show that
      rapid Tempol reduction correlates with decreased tumor oxygenation, and that the
      Tempol decay rate constant may be a surrogate marker for tumor hypoxia.

PMID- 23007800
TI  - Remobilization of polychlorinated biphenyls from sediment and its consequences
      for their transport in river waters.
AB  - A laboratory experiment was performed to examine the remobilization of indicator
      polychlorinated biphenyls (iPCBs) from sediments and its results were applied to
      the real-world data for explaining the transport of PCBs in river. Seven PCB
      concentrations were determined in three series of model water-sediment systems (3
      g of river sediment, three different volumes of distilled water (0.5, 0.25, and
      0.15 ml), and 5 mg of biocide) after 11 days of incubation. Solid-phase
      extraction was used for separation of analytes from the aqueous phase and solvent
      extraction for isolation of analytes from the sediments, respectively. The
      extracts were analyzed for individual iPCB congeners using gas chromatography
      mass spectrometry method. For each series of the experiment, the concentrations
      of PCBs in aqueous phase were similar. The average sediment/water partition
      coefficient value was 10(4) l/kg. The solubility of individual PCB congeners in
      water did not influence the desorption of PCBs from the sediment. Although the
      dominant form of PCBs in a water-sediment system occurs as suspended and
      colloidal fractions, these compounds are transported mostly in a dissolved form.
      Suspended and colloidal matter is a major sink for PCBs in low-energy aquatic
      environments. In contrast, the dissolved PCBs are readily transported in running
      waters. The mobilization of PCBs from sediments to aqueous phase, with respect to
      their solubility in water, seems to be limited, thus reducing the risk of
      secondary pollution.

PMID- 23007801
TI  - Physiologic responses and energy expenditure of kinect active video game play in
      schoolchildren.
AB  - OBJECTIVE: To evaluate the physiologic responses and energy expenditure of active
      video gaming using Kinect for the Xbox 360. DESIGN: Comparison study. SETTING:
      Kirkby Sports College Centre for Learning, Liverpool, England. PARTICIPANTS:
      Eighteen schoolchildren (10 boys and 8 girls) aged 11 to 15 years. MAIN EXPOSURE:
      A comparison of a traditional sedentary video game and 2 Kinect activity
      promoting video games, Dance Central and Kinect Sports Boxing, each played for 15
      minutes. Physiologic responses and energy expenditure were measured using a
      metabolic analyzer. MAIN OUTCOME MEASURES: Heart rate, oxygen uptake, and energy
      expenditure. RESULTS: Heart rate, oxygen uptake, and energy expenditure were
      considerably higher (P < .05) during activity-promoting video game play compared
      with rest and sedentary video game play. The mean (SD) corresponding oxygen
      uptake values for the sedentary, dance, and boxing video games were 6.1 (1.3),
      12.8 (3.3), and 17.7 (5.1) mL . min-1 . kg-1, respectively. Energy expenditures
      were 1.5 (0.3), 3.0 (1.0), and 4.4 (1.6) kcal . min-1, respectively. CONCLUSIONS:
      Dance Central and Kinect Sports Boxing increased energy expenditure by 150% and
      263%, respectively, above resting values and were 103% and 194% higher than
      traditional video gaming. This equates to an increased energy expenditure of up
      to 172 kcal . h-1 compared with traditional sedentary video game play. Played
      regularly, active gaming using Kinect for the Xbox 360 could prove to be an
      effective means for increasing physical activity and energy expenditure in
      children.

PMID- 23007802
TI  - CC motif chemokine ligand 13 is associated with rheumatoid arthritis
      pathogenesis.
AB  - OBJECTIVES: CC motif chemokines are considered to be implicated in the
      pathogenesis of rheumatoid arthritis (RA) via recruitment of monocytes and
      lymphocytes. CC motif chemokine ligand 13 (CCL13)/monocyte chemoattractant
      protein-4 (MCP-4) is postulated to be a potent RA inducer. We conducted a study
      to more precisely clarify the role of CCL13 in RA pathogenesis. METHODS: CCL13
      expression was evaluated by enzyme-linked immunosorbent assay (ELISA) and
      immunohistochemical staining in serum samples and synovial tissues from RA
      patients. The effects of CCL13 against apoptosis were monitored on cultured
      synovial fibroblasts. The chemoattractant activity of CCL13 was evaluated by the
      Boyden chamber assay in monocytes (THP-1 cells) and human umbilical vein
      endothelial cells (HUVECs). RESULTS: We found that CCL13 serum level and synovial
      tissue expression were increased in RA patients. CCL13 had chemoattractant
      activity for both THP-1 cells and HUVECs. Interestingly, CCL13 expression was
      positively regulated by tumor necrosis factor-alpha (TNF-alpha). Furthermore,
      apoptosis induced by hydrogen peroxide (H2O2) and serum deprivation was inhibited
      by CCL13 on the cultured synovial fibroblasts. CONCLUSIONS: CCL13 may be
      associated with disease progression as a result of its antiapoptotic effects,
      increased macrophage infiltration, and synovial tissue angiogenesis in RA
      patients.

PMID- 23007804
TI  - Intrapericardial mature cystic teratoma in an adult: case presentation.
AB  - Cardiac Teratoma is a tumor of very rare occurrence in adult population. Here we
      report a case in a Caucasian male with history of Human immunodeficiency virus
      infection where the symptom as presentation was recurrent episodes of
      tachycardia. The chest radiograph showed a lesion in the right heart border and
      subsequent investigation revealed an intrapericardial lesion, which was
      demonstrated to be a pericardial teratoma diagnosed by histopathology. In this
      case the initial differential diagnosis included lymphoma or an infectious
      organism as possible causes in a immunocompromised patient. Cardiac teratomas are
      among the less common types of cardiac tumors being more frequent in child
      population and around 1% of all the cardiac tumors in adults. Imaging studies are
      very helpful. CT and MRI are the best due to their resolution and ability to
      assess the relationship of the mass with the surrounding structures.
      Echocardiogram in also helpful determining the presence of pericardial effusion
      because cardiac teratomas are most of the time present in the pericardium. The
      final diagnosis is mostly made after surgical excision and this is the most
      effective treatment because they are relatively resistant to chemotherapy and
      radiotherapy.

PMID- 23007805
TI  - Naphthalene biomarkers and relationship with hemoglobin and hematocrit in White,
      Black, and Hispanic adults: results from the 2003-2004 National Health and
      Nutrition Examination Survey.
AB  - Naphthalene is an important contaminant in indoor and outdoor air. Acute
      overexposure can have toxic effects, resulting in hemolysis. There have been no
      studies evaluating the impact of environmental exposure on red blood cell
      indices. We examined 1- and 2-hydroxynaphthalene urinary metabolites (NAP1 and
      NAP2) in non-Hispanic White, non-Hispanic Black, and Mexican-American adults in
      the USA and their relationship with hemoglobin (Hb) and hematocrit (HCT). Using
      the 2003-2004 National Health and Nutrition Examination Survey data, weighted
      generalized linear regression analyses were used to examine the association
      between Hb (in grams per deciliter) and HCT (in percent) with NAP1 and NAP2 (per
      100,000 ng/L). Beta coefficients +/- SE are reported. NAP1 and NAP2 were highest
      in non-Hispanic Blacks, followed by non-Hispanic Whites, and lowest in Mexican
      American adults. There was a positive association between NAP1 and Hb (0.39 +/-
      0.11, p = 0.0034) and HCT (1.14 +/- 0.28, p = 0.0009) after adjusting for age,
      gender, race, education, and smoking. Stratified analysis by smoking showed
      similar results with the association being stronger for smokers (Hb 0.63 +/-
      0.23, p = 0.02; HCT 1.43 +/- 0.79, p = 0.09) than nonsmokers (Hb 0.34 +/- 0.14, p
      = 0.03; HCT 1.08 +/- 0.42, p = 0.02). The association was also stronger for non
      Hispanic blacks (Hb 0.54 +/- 0.20, p = 0.02; HCT 1.43 +/- 0.55, p = 0.02) than
      for non-Hispanic whites (Hb 0.37 +/- 0.18, p = 0.06; HCT 1.20 +/- 0.51, p = 0.03)
      and was not significant for Mexican-Americans (Hb 0.30 +/- 1.7, p = 0.10; HCT
      0.99 +/- 0.52, p = 0.08). NAP2 was not significantly associated with Hb or HCT.
      The observed disparity in NAP1 and NAP2 levels by race/ethnicity is consistent
      with published literature. The origin of these differences in exposure is unclear
      but may reflect differences in environmental exposure as well as genetic
      susceptibility. The positive association between NAP1 with HCT and Hb is an
      unexpected finding. Further research is needed to understand the possible
      biological mechanisms or other explanations for this association.

PMID- 23007807
TI  - The role of carrion in maintaining biodiversity and ecological processes in
      terrestrial ecosystems.
AB  - Carrion provides a resource for a subset of animal species that deliver a
      critical ecosystem service by consuming dead animal matter and recycling its
      nutrients. A growing number of studies have also shown various effects of carrion
      on different plant and microbial communities. However, there has been no review
      of these studies to bring this information together and identify priority areas
      for future research. We review carrion ecology studies from the last two decades
      and summarise the range of spatial and temporal effects of carrion on soil
      nutrients, microbes, plants, arthropods, and vertebrates. We identify key
      knowledge gaps in carrion ecology, and discuss how closing these gaps can be
      achieved by focusing future research on the (1) different kinds of carrion
      resources, (2) interactions between different components of the carrion
      community, (3) the ways that ecosystem context can moderate carrion effects, and
      (4) considerations for carrion management. To guide this research, we outline a
      framework that builds on the 'ephemeral resource patch' concept, and helps to
      structure research questions that link localised effects of carrion with their
      consequences at landscape scales. This will enable improved characterisation of
      carrion as a unique resource pool, provide answers for land managers in a
      position to influence carrion availability, and establish the ways that carrion
      affects the dynamics of species diversity and ecological processes within
      landscapes.

PMID- 23007806
TI  - Direct and indirect selection on floral pigmentation by pollinators and seed
      predators in a color polymorphic South African shrub.
AB  - The coexistence of different color morphs is often attributed to variable
      selection pressures across space, time, morph frequencies, or selection agents,
      but the routes by which each morph is favored are rarely identified. In this
      study we investigated factors that influence floral color polymorphisms on a
      local scale in Protea, within which approximately 40% of species are polymorphic.
      Previous work shows that seed predators and reproductive differences likely
      contribute to maintaining polymorphism in four Protea species. We explored
      whether selection acts directly or indirectly on floral color in two populations
      of Protea aurea, using path analysis of pollinator behavior, nectar production,
      seed predation, color, morphology, and maternal fecundity fitness components. We
      found that avian pollinators spent more time on white morphs, likely due to
      nectar differences, but that this had no apparent consequences for fecundity.
      Instead, the number of flowers per inflorescence underpinned many of the
      reproductively important differences between color morphs. White morphs had more
      flowers per inflorescence, which itself was positively correlated with nectar
      production, seed predator occurrence, and total long-term seed production. The
      number of seeds per plant to survive predation, in contrast, was not directly
      associated with color or any other floral trait. Thus, although color differences
      may be associated with conflicting selection pressures, the selection appears to
      be associated with the number of flowers per inflorescence and its unmeasured
      correlates, rather than with inflorescence color itself.

PMID- 23007808
TI  - Effect of tonsillar mononuclear cell supernatants in patients with IgA
      nephropathy on renal tubular epithelial cells.
AB  - OBJECTIVE: This study aimed to investigate the immunological relationship and the
      mechanism between tonsillar inflammation and immunoglobulin A nephropathy (IgAN).
      SUBJECTS: Tonsillar mononuclear cells (TMCs) were prepared from 13 patients with
      IgAN and 13 patients with chronic tonsillitis but without renal disease. The
      human renal tubular epithelial cell (TEC) line, HK-2, was used to test the
      effects of secretions from the TMCs. METHODS: Phytohemagglutinin (PHA) was used
      to induce the inflammatory responses in TMCs. The secretions from TMCs,
      stimulated with or without PHA, were collected and applied to HK-2 cells. The
      proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of HK-2
      cells were evaluated. The expression of key components during apoptosis and EMT
      was measured. RESULTS: The secretions from PHA-stimulated IgAN TMCs significantly
      inhibited proliferation, promoted apoptosis, and down-regulated Bcl-2 in HK-2
      cells (P < 0.05) in time- and concentration-dependent manners. They also
      modulated the expression of key components during EMT, E-cadherin and alpha-SMA
      (P < 0.05). CONCLUSIONS: The secretions from PHA-stimulated IgAN TMCs can cause
      the inhibition of proliferation, promotion of apoptosis, down-regulation of Bcl
      2, and EMT effects in HK-2 TECs, which may reflect the in-vivo remote modulation
      of functions of renal TECs by tonsillar inflammation.

PMID- 23007809
TI  - Pilot study of the effect of vitamin B6 on the motility of guinea pigs ileum:
      possible implications for human intestinal motility.
AB  - OBJECTIVES: To evaluate the effect of vitamin B6 and neostigmine on the
      intestinal motility of guinea pigs, to obtain beneficial effects on human health.
      MATERIALS AND METHODS: Segments of the ileum of guinea pigs have been removed and
      mounted in an organ bath in order to record their motility when treated with
      vitamin B6, atropine and neostigmine. This motility has been compared with the
      contraction produced by acetylcholine. These substances were injected into the
      cuvette of the apparatus both singularly and in combination. RESULTS: The
      isolated segments of the ileum of guinea pigs exposed to vitamin B6 (5.91 x 10(
      8) M) have asthenic contraction of 59.38 + 11.28 (mean + SD) compared with the
      peak observed for acetylcholine. When atropine (2.76 x 10(-7) M) was administered
      during the contraction produced by the vitamin B6, the contraction was blocked.
      Neostigmine (1.50 x 10(-5) M) on its own produced asthenic contraction 59.16 +
      10.11 (mean + SD) compared with the peak observed for acetylcholine. Neostigmine
      administered after vitamin B6 (5.91 x 10(-8) and 1.48 x 10(-7) M) produces a mean
      contraction of 104.50 + 8.77 and 108.8 + 12.65 (mean + SD) compared with
      acetylcholine. CONCLUSIONS: Data reported show that vitamin B6 has an effect on
      the motility of the ileum of guinea pigs. The contraction produced by the
      combination of vitamin B6 and neostigmine is greater and more prolonged than that
      produced by neostigmine alone. This association could improve the efficacy of
      neostigmine to resolve intestinal asthenia as quickly as possible to obtain
      beneficial effects on human health.

PMID- 23007810
TI  - Gender, lifestyles, illness perception and stress in stable atrial fibrillation.
AB  - AIMS: The study is aimed at investigating if perceived stress in Stable Atrial
      Fibrillation (AF) has any gender-associated feature and relationships with
      lifestyle indicators and education level, and which relationship self efficacy,
      anxiety and depression and illness perception have, if any. PATIENTS AND METHODS:
      88 consecutive patients referred for stable AF are studied by Psychological
      Stress Measure (PSM) test, Illness Perception Questionnaire (IPQ-R), Generalized
      Self-Efficacy scale (GSE) and Hospital Anxiety and Depression Scale (HADS).
      Mediterranean diet, physical activity increase and smoking withdrawal counseling
      were provided. RESULTS: AF patients have higher PSM associated with gender
      (women), older age, anxiety and depression. Higher GSE, greater Adherence to
      Mediterranean Diet profile and coffee habits (greater coffee users) are
      associated with a reduced hazard of perceived stress. By multiple linear
      regression, PSM is explained by Anxiety and IPQr (statistically significant are
      emotional representation and illness coherence subscales), which account for
      92.2% of the variance (p<0.0001). CONCLUSION: Our results outline that
      psychological stress is greater in women in comparison with men. Illness
      perceptions are important in the context of perceived stress in AF. This effect
      appears to be modulated by greater self-efficacy and by Adherence to
      Mediterranean Diet profile, that when higher, are associated with a reduced
      hazard of perceived stress. We suggest that therapeutic interventions on illness
      perceptions can be warranted in order to achieve a lower psychological distress
      in AF patients.

PMID- 23007811
TI  - Prevalence of iron deficiency anaemia and thalassaemia trait among undergraduate
      medical students.
AB  - BACKGROUND: Anaemia is a global health problem including Malaysia. In adults,
      anaemia may affect work productivity. Iron deficiency anaemia and thalassaemia
      are common causes of anaemia in Malaysia. However, there is scarcity of data on
      national prevalence of iron deficiency anaemia and thalassaemia, especially in
      young adults. This cross sectional study was performed to determine the
      prevalence of iron deficiency anaemia and thalassaemia among medical students of
      Universiti Kebangsaan Malaysia Medical Centre (UKMMC). MATERIALS AND METHODS:
      Blood samples collected in EDTA tubes were analyzed for haemoglobin level and red
      cell parameters such as MCV, MCH and red cell counts. Samples with abnormal red
      cell indices were sent for analysis of RBC morphology, iron status, haemoglobin
      analysis and DNA analysis. RESULTS: A total of 400 samples were available for
      this study. Fifty-eight (14.5%) students had hypochromic microcytic red cell
      indices in which 44 (11%) showed thalassaemia red cell indices while 14 (3.5%)
      had iron deficiency red cell indices which were finally confirmed by serum
      iron/TIBC analysis. Amongst those suspected to have thalassaemia, 12 (27.3%) were
      confirmed as alpha thalassaemia trait (alphaalpha/--(SEA)), 11 (25%) as
      Haemoglobin-E trait, 8 (18.2%) as beta thalassaemia trait and 2 (4.5%) as
      Haemoglobin Constant Spring (alphaalpha/alpha(CS)alpha). However, eleven students
      (25%) with thalassaemia red cell indices could not be confirmed with the common
      thalassaemia primers available, thus causes have yet to be established.
      CONCLUSION: Our prevalence of thalassaemia was high and thus we opine that better
      screening methods should be adopted.

PMID- 23007812
TI  - [Negative dimension, social cognition, insight and subjective experience in
      Schizophrenia].
AB  - INTRODUCTION: Investigation on subjective symptoms in schizophrenia has
      traditionally been limited to delusions and hallucinations, not considering the
      persistence of many others disorders and difficulties as residual negative
      symptoms and cognitive deficits that instead greatly affect the clinical and
      functional prognosis. The aim of the study is to investigate the differences
      between the subjective experience of the patient and the objective assessment
      regarding the negative dimension symptoms in patients with schizophrenia.
      MATERIALS AND METHODS: We evaluated 58 patients with a diagnosis of schizophrenia
      consecutively admitted at the L'Aquila Psychiatric inpatient ward (Italy) from
      April to September 2010; all of them were taking psychopharmacological treatment.
      The instruments used were: the PANSS for assessment of clinical symptoms and VGF
      for the assessment of the global functioning, the SENS, the Insight Self-Report
      Scale and the Scale Geople to investigate respectively the negative dimension
      subjectively perceived, the insight and the social cognition. RESULTS: The
      analysis of SENS showed a score of 95.43 (SD +/- 9.1) in the awareness, pointing
      to a negative perception of the experience medium to high. The study of Social
      Cognition has shown the presence of a statistically significant discrepancy
      between the two evaluations (p <0.01). The inferential analysis between SENS and
      PANSS, reported significant correlations between the PANSS negative symptoms of
      the item of inability to feel the SENS (p <0.015). Finally, a positive
      correlation was found between the total score of SENS with GFR (p <0.02).
      CONCLUSION: The knowledge of the subjective experiences of patients with
      schizophrenia can be difficult because of social withdrawal and resistance to
      treatment, due mostly to the subjective suffering that is not adequately
      understood. The results, in line with the recent literature, have shown that the
      perception of negative symptoms does not always find a parallel in the clinical
      assessment and how this is a significant correlation with the global functioning.
      In this perspective, it is therefore necessary to consider the point of view of
      the patient in order to predict the adherence to the treatment and the global
      functioning outcome.

PMID- 23007813
TI  - Stress, abdominal obesity and intrarenal resistive index in essential
      hypertension.
AB  - AIM: Although it is commonly believed that a strong causal link exists between
      psychological stress and hypertension, as well with other factors, such as
      obesity, just what kind of empirical evidence supports this assumption is still
      controversial. The aim of the study is to investigate if perceived stress have
      any interference with intrarenal resistance and hence with mechanisms related to
      Essential Hypertension (EH) and if Anxiety, Depression, Self efficacy and Illness
      Perception can account for perceived stress. PATIENTS AND METHODS: Obesity,
      insulin resistance (HOMA), Doppler Renal Resistive Index (RRI) and glomerular
      filtration rate (GFR) are studied along with Psychological Stress Measure (PSM),
      Illness Perception Questionnaire (IPQ-R), Generalized Self-Efficacy scale (GSE)
      and Hospital Anxiety and Depression Scale (HADS) in 119 hypertensive patients
      referred for stable lasting EH, and 150 normal controls. Lower salt/lower
      calories Mediterranean diet, physical activity increase and smoking withdrawal
      counseling were provided. RESULTS: By Odds Ratios, higher risk of EH is
      associated with greater perceived stress, older age, lower GFR, obesity, greater
      RRI and insulin resistance. By Multiple Linear Regression the most significant
      variable that accounts for higher RRI are abdominal obesity and arterial pulse
      pressure; the only significant independent psychological variable that accounts
      for abdominal obesity are PSM and identity IPQ subscale. Self-Efficacy anxiety
      and Illness perception subscales (IPQr), accounts significantly for 62.0% of the
      variance to PSM, with possible effects on RRI and on the pathophysiological
      hypertension cascade. CONCLUSION: Worst identity and treatment control
      perceptions of EH, and a lower self-efficacy are the main psychological factors
      accounting for a greater stress. Interventions aimed to reduce perceived stress
      can be warranted in EH.

PMID- 23007814
TI  - Peroneus quartus, an accessory muscle in human: case report and its clinical
      importance.
AB  - The peroneus quartus is an accessory peroneal muscle seen in man. The term
      'peroneus quartus' is often used to refer one or several of the accessory
      peroneal muscles. In this case, we report an unusual type of peroneus quartus
      which was originating from the muscular portion of the peroneus brevis and
      inserting onto the peroneus longus tendon. The clinical implications are
      emphasized with the morphological significance and literature review. The
      orthopedic surgeons and radiologists should be aware of the possible presence of
      this muscle not only because of its associated pathology, but also for its
      potential use in plastic surgeries.

PMID- 23007815
TI  - Descending thoracic mycotic aneurysm: successful treatment with endovascular
      stenting.
AB  - Mycotic descending thoracic aneurysm with aortobronchial fistula is a rare
      condition which is associated with high mortality. Treatment in the era of
      minimally invasive procedure can often be controversial. The risk of graft
      infection should be considered as well as the unknown long term behavior of the
      endovascular stent. Here, we describe our initial experience of performing
      emergency thoracic endovascular aneurysm repair in an unstable patient presenting
      with haemoptysis.

PMID- 23007816
TI  - [Atheroembolism renal disease: diagnosis and etiologic factors].
AB  - Atheromatous renal disease is the major cause of renal insufficiency in the
      elderly, and cholesterol embolism is a manifestation of this disease. Cholesterol
      embolism occurs in patients suffering from diffuse erosive atherosclerosis,
      usually after triggering causes, such as aortic surgery, arterial invasive
      procedures (angiography, left heart catheterization and coronary angioplasty) and
      anticoagulant or thrombolytic therapy. It is characterized by occlusion of small
      arteries with cholesterol emboli deriving from eroded atheromatous plaques of the
      aorta or large feeder arteries. The proximity of the kidneys to the abdominal
      aorta and the large renal blood supply make the kidney a frequent target organ
      for cholesterol atheroembolism. The exact incidence of atheroembolic renal
      disease (AERD) is not known. The reported incidence AERD varied in the literature
      because of the differences in study design and the different criteria used for
      making the diagnosis. Retrospective data derived from autopsy or biopsy studies
      may exaggerate the frequency by including many subclinical cases. Clinical
      observations that are based on a short duration of follow-up after an invasive
      vascular procedure and the infrequency of the confirmatory renal biopsies can
      lead to an underestimation of the true incidence of AERD. The initial signs and
      symptoms in patients diagnosed with cholesterol embolism were blue toes syndrome,
      livedo reticularis, gangrene, leg, toe or foot pain, abdominal pain and flank or
      back pain, gross haematuria, accelerated hypertension and renal failure.
      Cholesterol embolism may also be associated with fever, increased erythrocyte
      sedimentation rate and eosinophilia. Thus, in the cases of spontaneous
      cholesterol embolism, differential diagnosis includes, polyarteritis nodosa,
      allergic vasculitis and subacute bacterial endocarditis. Skin and renal biopsy
      specimens are the best sample for histologic diagnosis. There is, at present, no
      pharmacological treatments shown to be effective in altering the course of the
      disease. Management is limited to supportive therapy and avoidance of
      anticoagulation; aortic procedures should be postponed.

PMID- 23007817
TI  - Hospital communication between perception and cost savings: an Italian case
      study.
AB  - BACKGROUND: Communication field is very much studied by Companies but not so much
      from the Italian NHS. We aim to study the suffering communication that patients,
      relatives and customers feel when they approach a hospital. The research was
      carried out in an Italian region: Lazio. The Objective was to take a picture of
      the current state of Regional Health-Care System (RHS) communication by local
      Visual Communication (VC), telematic, internal perception, communication
      propensity and perception of hospital's brand. MATERIALS AND METHODS: We have
      sampled 7 hospitals (114 items): Web-site's analysis, Location's VC, Urp's
      manager interview, Focus-group, Analysis Valuator of the Hospital's Brand
      (AVoHB). RESULTS: WEB: 14% of web-sites had a positive score, 86% had an Hospital
      Service Guide, 43% hadn't Urp's e-mail, 29% had a ward's map, 0% was W3C.
      Average: -17pt. on +/-74pt. VISUAL COMMUNICATION: 100% had a Help-desk at the
      entrance, 100% had readable signpost, 43% had a readable badge, 29% had chromatic
      signpost, 0% had an assistance signpost and none of them had the Toilettes
      signpost. Average: -10,42pt. on +/-58pt. FOCUS-GROUP: Staff underline their very
      high interest in interpersonal communication. They report a lack of VC inside
      their hospitals that cannot help patients to be self-oriented. Lost users can
      only ask information to the first doctor they see, taking staff time, which is
      already lacked. AVOHB: Powergrid shows that the positioning of the Aggregated
      Brand (RHS) and of each hospital analyzed are in the III quadrant. CONCLUSIONS:
      By a Corporate Communication point of view we can see that almost all companies
      reach a good level in terms of effective communication but none of them excel in
      all critical areas for an effective communication.

PMID- 23007818
TI  - Organization, achievement and results of a pelvis surgery center.
AB  - INTRODUCTION: Pelvic fractures are not frequent, yet severe injuries, often
      associated to other lesions. Well defined diagnostic and therapeutic procedures
      are lacking, and their economical assessment is inadequate. The goal of this
      study is to propose the organization of a multidisciplinary center that can
      develop diagnosis, treatment, and follow up protocols. MATERIALS AND METHODS: 25
      patients were treated from August 2008 to July 2010, 5 women and 20 men, average
      age 34.5 years. Twenty patients had acetabular fractures (8 posterior wall
      fractures, 2 anterior column fractures and 10 mixed fractures, Judet and
      Letournel). Five patients suffered from diastasis symphisis pubis (three patients
      with a CAP type I, and 2 with a CAP type II, Young-Burgess). RESULTS: Average
      delay between trauma and operation was 15.6 days. Average hospital stay after
      surgery was 45 days. Five had excellent results, 15 were good, and 4 presented
      poor results. One patient deceased. Four patients underwent hip arthroplasty 1
      year after surgery. DISCUSSION: It was essential to identify the collaborating
      units. The center aims at a uniform and rapid treatment for patients with lesions
      which are treated differently depending on the department of hospitalization and
      on the surgeon's experience. The target is to avoid treatment delays, costs and
      complications. The DRG evaluation grants the highest value to pelvis surgery.
      This should be followed by dedicated structures that can become reference
      centers. CONCLUSION: The results can be improved, but considering this is not
      well known context both clinically and economically, they can be seen positively.

PMID- 23007819
TI  - Simultaneous primary gastric and duodenal MALT lymphoma presenting with
      gastrointestinal bleeding.
AB  - The gastrointestinal tract, particularly the stomach, is the most common site of
      mucosa-associated lymphoid tissue lymphoma (MALToma). Many studies describe
      primary MALT lymphoma arising from the gastric mucosa, especially in association
      with Helicobacter pylori infection. On the contrary, primary MALT duodenal
      lymphoma is a very rare neoplasm. We report a case of a patient with
      gastrointestinal bleeding in whom primary gastric and duodenal MALT lymphoma were
      occurred simultaneously.

PMID- 23007820
TI  - Corneal haze in course of Fuchs' endothelial dystrophy.
AB  - This article describes the observations obtained with confocal microscopy (CM) on
      the corneal structure in course of corneal edema in a patient with Fuchs
      endothelial corneal dystrophy (FD). The patient was a 40 year old male, suffering
      from second stage FD, in course of corneal edema and bullous keratopathy. The
      tissue structure was analyzed with CM confoscan CS4 (Nidek Technologies((r)),
      Birmingham, UK) using the 40x mode. The CM has shown the presence of gaps due to
      corneal edema and a diffuse stromal hyper reflectivity related to the alteration
      of the extracellular matrix. It has also showed the presence of binucleate cells,
      assimilable to keratocytes, in cytokinesis which presented a typical fusiform
      aspect with two highly reflective nuclei awaiting cell division. The total number
      of cells was much lower than that of healthy control subjects of similar age, sex
      and race. The CM in this case suggests a significantly lower number of cells,
      presumably keratocytes, compared to normal range, but mostly it shows the
      presence of cells undergoing cytokinesis, which witnesses the active processes of
      collagenogenesis and possible vasculogenesis that represent early stages of loss
      of the normal corneal transparency.

PMID- 23007821
TI  - Atipic pigmented retinitis: a case report.
AB  - The Authors describe a clinical case of pigmented paravenous retinochoroidal
      atrophy in a young patient (12 years old). In the mid-peripheral area spots of
      accumulated pigment were observed, in particular along the veins. The exams are:
      funduscopy, elettroretinogram. The already examined pathology is an inherited
      retinic dystrophy with an uncertain transmission. According to Literature a young
      male case his described. Because of rarity, it is impossible describe hereditary
      transmission mechanism.

PMID- 23007822
TI  - [Rupture of the right ventricular wall closed with Daflon patching and biological
      glue].
AB  - In this paper we present a rare case of Dacron patch closure of tear in right
      ventricular myocardial at outflow level, caused by stroke of hypoplastic right
      coronary artery occlusion, in patient with non-obstructive hypertrophic
      cardiomyopathy caused by hypertension and aortic stenosis, surgically treated by
      implantation of mechanical prostheses, and pericarditis postcardiotomy. Our
      purpose is to trace evidence from postmortem identification of pathogenic
      mechanisms occurring in causing fatal event. The severe myocardial hypertrophy
      observed is supposedly based on valvular or hypertensive, is compatible with a
      significant reduction of the diastolic function and with the genesis of acute
      pulmonary edema as a trigger: the latter case may result in death for the
      reduction of contractile reserve of the right ventricle, induced by the presence
      of the patch surgically implanted.

PMID- 23007823
TI  - [Gastric leiomyosarcoma: case report and review of literature].
AB  - True smooth muscle neoplasms of the wall of digestive tract are rare, in
      particular in the stomach, and the benign ones are prevalent. We report a case of
      gastric leiomyosarcoma (LMS) that we observed, diagnosed to a 71 years-old man,
      with important comorbidities, who had already underwent the amputation of the
      right lower limb. In consequence of the discovery of anaemia and melaena he
      underwent an endoscopy of the upper GI tract and CT scan, which showed the
      presence of a neoformation of the gastric wall, but because of the thrombosis of
      the common iliac artery and the occurrence of the clinical picture of critical
      ischaemia, at first the patient underwent the amputation of the left lower limb e
      only then an intervention of atypical gastroresection. Despite the neoplastic
      infiltration of the resection margins and the impossibility to undertake an
      adjuvant chemotherapy, the follow-up at 6, 12 and 28 months did not show a
      recurrence of the disease that remained in phase of clinical remission.

PMID- 23007824
TI  - [Bernard-Horner syndrome after accidental lesion of carotid artery: case report].
AB  - Among the complications of internal jugular vein insertion there is the lesion of
      the cervical sympathetic trunk with the onset of Bernard-Horner syndrome,
      consisting of miosis, eyelid ptosis, enophthalmos and anhidrosis on the same side
      of the lesion. The neurological damage can be caused by the direct puncture of
      the trunk or by the irritating and compressive action of a hematoma during the
      puncture of the internal jugular; the clinical picture, when reversible, resolves
      in a few months. The case we report is about the onset of the syndrome after
      accidental puncture of carotid artery, followed by the total disappearance of
      signs in a few days.

PMID- 23007825
TI  - [ADHD or childhood-onset schizophrenia? A case report].
AB  - In the last decades there was an increasing interest in early detection of
      prodromal symptoms in schizophrenia and, more specifically, in detecting subjects
      at high risk for psychosis. However, especially in case of childhood-onset
      schizophrenia (COS), sometimes it is possible to don't recognize its early
      symptoms and to ascribe the observed clinical picture to other diseases, with
      consequent delay in diagnosis and treatment of these patients. In this case
      report we want to underline the importance of an early detection of
      schizophrenia, with a focus on differential diagnosis between Attention
      Deficit/Hyperactivity Disorder and schizophrenia.

PMID- 23007826
TI  - [Appropriateness prescribing and doctor's professional responsibility].
AB  - The public health spending has now reached very significant levels, in this
      sense, the responsibility of the medical doctor assumes a significant importance
      in medical law. The aim of this paper is to analyze the profile of
      responsibilities of the medical doctor in the light of recent case law. The
      appropriateness of prescribing and risk assessment are, according to the authors,
      the real test on which to test the skill, prudence and diligence which are called
      prescribers. Guidelines can be a valuable tool for the professional help,
      knowing, however, limits application of the recommendations where to be
      reconciling with the prevailing protection of personal rights of the user.

PMID- 23007827
TI  - [Stress and information-communication technologies: from videoterminal to web].
AB  - The relationship between stress and new technologies has always been a vexed
      question. Sociologists and philosophers say technology is a double edged sword,
      on one hand it increases the potential of human senses, while on the other hand
      it forces man to adopt rhythms and conditions not natural but artificial, with
      consequences for his physical and mental health. Modern Cognitive Ergonomic tries
      to analyze to technology, interacting with mental functions, causes stress and it
      tries to offer the most appropriate technological solutions for human work. From
      our analysis it emerges that the old media have an influence on mood causing
      episodes of insomnia, irritability, anxiety, etc., even if in a way that cannot
      be completely evaluated. Contrariwise, a controlled use of the web can improve
      the communication and the interacting abilities in patients with psychosocial
      distress and low social skills. Nielsen's Heuristics are a great tool to value
      methods of informatical and media interfaces.

PMID- 23007828
TI  - [Psychiatric emergencies: guidelines for the treatment of agitation].
AB  - Psychomotor agitation represents a common phenomenon in emergency psychiatry
      settings. The awareness of its clinical manifestations and the early management
      can permit the control over a potentially dangerous behavior that could otherwise
      convert itself into a violent one. Health professionals should be able to adopt
      de-escalation strategies, structured to achieve the stabilization of patients'
      aggressiveness and motor agitation. When abnormal behaviors persist clinicians
      should be competent in the adoption of the most adequate psychopharmacological
      treatment for patient de-escalation. In this work we analyze psychomotor
      agitation treatment guide-lines.

PMID- 23007829
TI  - [The perceived quality of routine daily communication in dialogues between health
      care workers].
AB  - In our day-to-day professional experience as doctors and chemists, we have often
      noted the poor quality of communication between us and other healthcare workers.
      We have observed how this in turn can adversely affect communication with the
      patient, which not only results in poor service to patients themselves, but also
      impairs the quality of our own work. Moreover, we are convinced that certain such
      behaviours are ubiquitous. We have therefore sought to evaluate this aspect of
      our professional life, using literature available on-line. The results reveal the
      existence of a large number of publications dedicated to relationships between
      different professions, and representing every possible position: from those
      frankly critical of other healthcare workers, to those seeking simply to
      understand these phenomena, to those planning strategies to overcome long-lasting
      animosities. Even the Italian Health Ministry, in its treatment of themes related
      to clinical risk, has devoted considerable attention to the quality of
      communication between healthcare workers. The conclusion we have reached is that
      there are two areas which are crucial to the improvement of inter-professional
      relations, namely: sufficient training in these matters in University courses,
      and a shift in conflicting ethical positions, which often reflect individual
      professional experience.

PMID- 23007830
TI  - [Revisiting iatrogenic damage in pneumology past and current implications
      compared].
AB  - Current features of iatrogenic damage by pneumological practice are taken into
      account and compared with those traced in the past by Daddi and colleagues. The
      Authors stress the major chances occurred over time and moreover they emphasize
      the correlated implications that took place with prevention, therapies, informed
      consent and defensive medicine. Especially in oncological as well as non
      oncological field the more relevant iatrogenic damages are represented by the
      pulmonary interstitial disease and pulmonary thromboembolism. However, from the
      revisiting is emerged that at present time are strongly increased the possibility
      and the means for preventing the onset of iatrogenic damage as well as the
      possibility of reducing the size of lesions consequent upon the pharmacological,
      surgical and radiotherapeutics treatments.

PMID- 23007831
TI  - [Drug abuse and adolescence: neurobiology and psychiatric implications].
AB  - Drug abuse in adolescence is a main public health concern. About 60% of people
      who abuse substances is younger than 18 years old. Early addiction increases
      other drug abuse and it is associated to greater risk in the development of
      Substance Use Disorders and psychiatric disorders. In the management of
      adolescent addiction, the awareness of recent researches on alcohol, cannabis,
      cocaine and methamphetamine abuse, can represent a fundamental tool in terms of
      prevention, early detection and treatment for clinicians, researches and parents.

PMID- 23007832
TI  - Reboxetine in clinical practice: a review.
AB  - Reboxetine is a selective noradrenaline reuptake inhibitor (NaRI), the first drug
      of a new antidepressant class. Reboxetine has been approved for the treatment of
      Major Depression in many European countries, but the application for approval was
      rejected in the United States. It has been found useful in Narcolepsy, ADHD,
      Panic Attack Disorder, treatment of depression in patients with Parkinson' s
      Disease. Moreover reboxetine has been proposed as an effective and safe
      therapeutic option for Cocaine Dependence Disorder. Despite a large number of
      studies have documented that reboxetine was equally effective in treating major
      depressive illness compared to other antidepressants, recent reports argue
      reboxetine to be ineffective and potentially harmful for the treatment of acute
      depression. Aim of the present review is to summarize and discuss the last
      literature findings, comparing risks and benefits of reboxetine usage in everyday
      clinical practice.

PMID- 23007833
TI  - Cloning and characterization of a Delta9-desaturase gene of the Antarctic fish
      Chionodraco hamatus and Trematomus bernacchii.
AB  - Chionodraco hamatus and Trematomus bernacchii are perciforms, members of the fish
      suborder Notothenioidei that live in the Antarctic Ocean and experience very cold
      and persistent environmental temperature. These fish have biochemical and
      molecular features that allow them to live at these extreme cold temperatures.
      Fine tuning of the level of unsaturated fatty acids content in membrane is a key
      mechanism of living organisms to adapt to cold and high temperatures. Desaturases
      are key enzymes that synthesize unsaturated fatty acyl-CoAs from saturated fatty
      acids. We cloned and sequenced a Delta(9)-desaturase gene and its cDNA of C.
      hamatus, and the cDNA of T. bernacchii. The coded proteins are virtually
      identical and share homology to other Delta(9)-desaturase fish sequences. These
      proteins contain, in the first trans-membrane domain, two cysteine residues that
      may form a disulfur bond present in the corresponding membrane region of Delta(9)
      desaturase proteins of other Antarctic fish but not in Eleginops maclovinus that
      experiences higher environmental temperatures and in all other Delta(9)
      desaturase genes of mammals present in data bases. C. hamatus Delta(9)-desaturase
      gene complements a Saccharomyces cerevisiae mutant lacking Delta(9)-desaturase
      (Ole1) gene. Analysis of sequence homology of the trans-membrane domains of
      Delta(9)-desaturase and the cytoplasmic region of the same proteins of Antarctic
      fish, non-Antarctic fish and mammals suggest that the significant differences
      found in the homologous sequences of the first trans-membrane domain may be due
      to the specific lipid content of their membrane.

PMID- 23007834
TI  - The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and
      bifenthrin.
AB  - Pyrethroids are highly toxic to fish at parts per billion or parts per trillion
      concentrations. Their intended mechanism is prolonged sodium channel opening, but
      recent studies reveal that pyrethroids such as permethrin and bifenthrin also
      have endocrine activity. Additionally, metabolites may have greater endocrine
      activity than parent compounds. The authors evaluated the in vivo concentration
      dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen
      responsive protein) in Menidia beryllina, a fish species known to reside in
      pyrethroid-contaminated aquatic habitats. The authors then compared the in vivo
      response with an in vitro assay--chemical activated luciferase gene expression
      (CALUX). Juvenile M. beryllina exposed to bifenthrin (1, 10, 100 ng/L),
      permethrin (0.1, 1, 10 ug/L), and ethinylestradiol (1, 10, 50 ng/L) had
      significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate
      than controls. Though Chg expression in fish exposed to ethinylestradiol (EE2)
      exhibited a traditional sigmoidal concentration response, curves fit to Chg
      expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing
      slightly as concentration increases. Whereas the in vivo response indicated that
      bifenthrin and permethrin or their metabolites act as estrogen agonists, the
      CALUX assay demonstrated estrogen antagonism by the pyrethroids. The results,
      supported by evidence from previous studies, suggest that bifenthrin and
      permethrin, or their metabolites, appear to act as estrogen receptor (ER)
      agonists in vivo, and that the unmetabolized pyrethroids, particularly
      bifenthrin, act as an ER antagonists in cultured mammalian cells.

PMID- 23007835
TI  - Neurological complications of Behcet's syndrome.
AB  - Behcet's syndrome is an autoinflammatory disease of uncertain cause characterized
      by mucous membrane ulceration, arthritis and inflammation within most tissues.
      Its prevalence differs throughout different populations, but neurological
      complications arise in 10 % of all those affected. The majority develop
      inflammation within the central nervous system which may remit but may also
      progressively worsen without treatment. This article reviews the epidemiology,
      clinical characteristics, natural history and management of the disorders, and
      emphasizes recent considerable advances in our understanding of the various
      treatments which may be beneficial across the spectrum of disease types.

PMID- 23007836
TI  - Synthesis of phase-shift nanoemulsions with narrow size distributions for
      acoustic droplet vaporization and bubble-enhanced ultrasound-mediated ablation.
AB  - High-intensity focused ultrasound (HIFU) is used clinically to thermally ablate
      tumors. To enhance localized heating and improve thermal ablation in tumors,
      lipid-coated perfluorocarbon droplets have been developed which can be vaporized
      by HIFU. The vasculature in many tumors is abnormally leaky due to their rapid
      growth, and nanoparticles are able to penetrate the fenestrations and passively
      accumulate within tumors. Thus, controlling the size of the droplets can result
      in better accumulation within tumors. In this report, the preparation of stable
      droplets in a phase-shift nanoemulsion (PSNE) with a narrow size distribution is
      described. PSNE were synthesized by sonicating a lipid solution in the presence
      of liquid perfluorocarbon. A narrow size distribution was obtained by extruding
      the PSNE multiple times using filters with pore sizes of 100 or 200 nm. The size
      distribution was measured over a 7-day period using dynamic light scattering.
      Polyacrylamide hydrogels containing PSNE were prepared for in vitro experiments.
      PSNE droplets in the hydrogels were vaporized with ultrasound and the resulting
      bubbles enhanced localized heating. Vaporized PSNE enables more rapid heating and
      also reduces the ultrasound intensity needed for thermal ablation. Thus, PSNE is
      expected to enhance thermal ablation in tumors, potentially improving therapeutic
      outcomes of HIFU-mediated thermal ablation treatments.

PMID- 23007837
TI  - Don't run before you can walk.

PMID- 23007838
TI  - Hanging in the balance: endogenous anti-inflammatory mechanisms in tissue repair
      and fibrosis.
AB  - Inflammation is the physiological response to tissue injury caused by pathogens
      or trauma. Nevertheless, inflammation should be resolved in a timely manner,
      resulting in elimination of the inflammatory cells and mediators from the injured
      tissue, to avoid its deleterious consequences. Uncontrolled inflammation can lead
      to inflammatory, autoimmune, and cancerous disorders that are the result of
      improper resolution. The healing of the injured tissue during the termination of
      inflammation must also be tightly controlled since excessive tissue repair can
      lead to fibrosis and scarring of the affected organ. In the last three decades,
      it has been revealed that the resolution of inflammation is tightly orchestrated
      by specific cells, protein, and lipid mediators that are produced at proper
      timing and distinct locations. The bioactivity of these anti-inflammatory, pro
      resolving, and immunoregulatory agents results in clearance of the tissue from
      inflammatory leukocytes and their products, and the return of homeostatic tissue
      architecture and function. Here, we will survey the current endogenous mechanisms
      governing the resolution of inflammation and directing it towards injury healing
      and halting of acquired immune responses while preventing excessive tissue repair
      and fibrosis. We focus on the role played by apoptotic polymorphonuclear cells
      (PMNs), 15-lipoxygenase (LO)-derived lipid mediators, and TGFbeta in this
      macrophage-governed decision-making process and suggest new modes of action for
      fibrosis prevention and return to homeostasis.

PMID- 23007840
TI  - Contribution of bi-allelic germline MUTYH mutations to early-onset and familial
      colorectal cancer and to low number of adenomatous polyps: case-series and
      literature review.
AB  - In the absence of a polyposis phenotype, colorectal cancer (CRC) patients
      referred for genetic testing because of early-onset disease and/or a positive
      family history, typically undergo testing for molecular signs of Lynch syndrome
      in their tumors. In the absence of these signs, DNA testing for germline
      mutations associated with other known tumor syndromes is usually not performed.
      However, a few studies in large series of CRC patients suggest that in a small
      percentage of CRC cases, bi-allelic MUTYH germline mutations can be found in the
      absence of the MUTYH-associated polyposis phenotype. This has not been studied in
      the Dutch population. Therefore, we analyzed the MUTYH gene for mutations in 89
      patients with microsatellite-low or stable CRC cancer diagnosed before the age of
      40 years or otherwise meeting the Bethesda criteria, all of them without a
      polyposis phenotype. In addition, we studied a series of 693 non-CRC patients
      with 1-13 adenomatous colorectal polyps for the MUTYH hotspot mutations Y179C,
      G396D and P405L. No bi-allelic MUTYH mutations were observed. Our data suggest
      that the contribution of bi-allelic MUTYH mutations to the development of CRC in
      Dutch non-polyposis patients that meet clinical genetic referral criteria, and to
      the development of low number of colorectal adenomas in non-CRC patients, is
      likely to be low.

PMID- 23007841
TI  - Agreement between Bayley Scales second and third edition assessments of very low
      birth-weight infants.

PMID- 23007842
TI  - Sumoylation in neurodegenerative diseases.
AB  - The yeast SUMO (small ubiquitin-like modifier) orthologue SMT3 was initially
      discovered in a genetic suppressors screen for the centromeric protein Mif2
      (Meluh and Koshland in Mol Bio Cell 6:793-807, 1). Later, it turned out that the
      homologous mammalian proteins SUMO1 to SUMO4 are reversible protein modifiers
      that can form isopeptide bonds with lysine residues of respective target proteins
      (Mahajan et al. in Cell 88:97-107, 2). This was the discovery of a post
      translational modification called sumoylation, which enzymatically resembles
      ubiquitination. However, very soon it became clear that SUMO attachments served a
      far more diverse role than ubiquitination. Meanwhile, numerous cellular processes
      are known to be subject to the impact of SUMO modification, including
      transcription, protein targeting, protein solubility, apoptosis or activity of
      various enzymes. In many instances, SUMO proteins create new protein interaction
      surfaces or block existing interaction domains (Geiss-Friedlander and Melchior in
      Nat Rev in Mol Cell Biol 8:947-956, 3). For the past few years, sumoylation
      attracted increasing attention as a versatile regulator of toxic protein
      properties in neurodegenerative diseases. In this review, we summarize the
      growing knowledge about the involvement of sumoylation in neurodegeneration, and
      discuss the underlying molecular principles affected by this multifaceted and
      intriguing post-translational modification.

PMID- 23007843
TI  - Extensive characterization of sphere models established from colorectal cancer
      cell lines.
AB  - Links between cancer and stem cells have been proposed for many years. As the
      cancer stem cell (CSC) theory became widely studied, new methods were developed
      to culture and expand cancer cells with conserved determinants of "stemness".
      These cells show increased ability to grow in suspension as spheres in serum-free
      medium supplemented with growth factors and chemicals. The physiological
      relevance of this phenomenon in established cancer cell lines remains unclear.
      Cell lines have traditionally been used to explore tumor biology and serve as
      preclinical models for the screening of potential therapeutic agents. Here, we
      grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines.
      The molecular and cellular characteristics of CFS were compared to the bulk of
      tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and
      their parental CRC cell lines were highly tumorigenic. Compared to their parental
      cells, they showed similar expression of putative CSC markers. The ability of CRC
      cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil.
      At the molecular level, CFS and parental CRC cells showed identical gene
      mutations and very similar genomic profiles, although microarray analysis
      revealed changes in CFS gene expression that were independent of DNA copy-number.
      We identified a CFS gene expression signature common to CFS from all CRC cell
      lines, which was predictive of disease relapse in CRC patients. In conclusion,
      CFS models derived from CRC cell lines possess interesting phenotypic features
      that may have clinical relevance for drug resistance and disease relapse.

PMID- 23007845
TI  - Robustness of signal transduction pathways.
AB  - Signal transduction pathways transduce information about the outside of the cell
      to the nucleus, regulating gene expression and cell fate. To reliably inform the
      cell about its surroundings, information transfer has to be robust against
      typical perturbation that a cell experiences. Robustness of several mammalian
      signaling pathways has been studied recently by quantitative experimentation and
      using mathematical modeling. Here, we review these studies, and describe the
      emerging concepts of robustness and the underlying mechanisms.

PMID- 23007844
TI  - Molecular mechanisms of melatonin's inhibitory actions on breast cancers.
AB  - Melatonin is involved in many physiological functions and it plays an important
      role in many pathological processes as well. Melatonin has been shown to reduce
      the incidence of experimentally induced cancers and can significantly inhibit the
      growth of some human tumors, namely hormone-dependent cancers. The anticancer
      effects of melatonin have been observed in breast cancer, both in in vivo with
      models of chemically induced rat mammary tumors, and in vitro studies on human
      breast cancer cell lines. Melatonin acts at different physiological levels and
      its antitumoral properties are supported by a set of complex, different
      mechanisms of action, involving apoptosis activation, inhibition of
      proliferation, and cell differentiation.

PMID- 23007847
TI  - Alzheimer's disease risk factor lymphocyte-specific protein tyrosine kinase
      regulates long-term synaptic strengthening, spatial learning and memory.
AB  - The lymphocyte-specific protein tyrosine kinase (Lck), which belongs to the Src
      kinase-family, is expressed in neurons of the hippocampus, a structure critical
      for learning and memory. Recent evidence demonstrated a significant
      downregulation of Lck in Alzheimer's disease. Lck has additionally been proposed
      to be a risk factor for Alzheimer's disease, thus suggesting the involvement of
      Lck in memory function. The neuronal role of Lck, however, and its involvement in
      learning and memory remain largely unexplored. Here, in vitro electrophysiology,
      confocal microscopy, and molecular, pharmacological, genetic and biochemical
      techniques were combined with in vivo behavioral approaches to examine the role
      of Lck in the mouse hippocampus. Specific pharmacological inhibition and genetic
      silencing indicated the involvement of Lck in the regulation of neuritic
      outgrowth. In the functional pre-established synaptic networks that were examined
      electrophysiologically, specific Lck-inhibition also selectively impaired the
      long-term hippocampal synaptic plasticity without affecting spontaneous
      excitatory synaptic transmission or short-term synaptic potentiation. The
      selective inhibition of Lck also significantly altered hippocampus-dependent
      spatial learning and memory in vivo. These data provide the basis for the
      functional characterization of brain Lck, describing the importance of Lck as a
      critical regulator of both neuronal morphology and in vivo long-term memory.

PMID- 23007849
TI  - Rotamer decomposition and protein dynamics: efficiently analyzing dihedral
      populations from molecular dynamics.
AB  - Molecular mechanics methods have matured into powerful methods to understand the
      dynamics and flexibility of macromolecules and especially proteins. As
      multinanosecond to microsecond length molecular dynamics (MD) simulations become
      commonplace, advanced analysis tools are required to generate scientifically
      useful information from large amounts of data. Some of the key degrees of freedom
      to understand protein flexibility and dynamics are the amino acid residue side
      chain dihedral angles. In this work, we present an easily automated way to
      summarize and understand the relevant dihedral populations. A tremendous
      reduction in complexity is achieved by describing dihedral timeseries in terms of
      histograms decomposed into Gaussians. Using the familiar and widely studied
      protein lysozyme, it is demonstrated that our approach captures essential
      properties of protein structure and dynamics. A simple classification scheme is
      proposed that indicates the rotational state population for each dihedral angle
      of interest and allows a decision if a given side chain or peptide backbone
      fragment remains rigid during the course of an MD simulation, adopts a converged
      distribution between conformational substates or has not reached convergence yet.

PMID- 23007846
TI  - Heat stress response of male germ cells.
AB  - The vast majority of mammalian testes are located outside the body cavity for
      proper thermoregulation. Heat has an adverse effect on mammalian spermatogenesis
      and eventually leads to sub- or infertility. Recent studies have provided
      insights into the molecular response of male germ cells to high temperatures.
      Here, we review the effects of heat on male germ cells and discuss the mechanisms
      underlying germ cell loss and impairment. We also discuss the role of
      translational control in male germ cells as a potential protective mechanism
      against heat-induced germ cell apoptosis. 

PMID- 23007848
TI  - A Smurf1 tale: function and regulation of an ubiquitin ligase in multiple
      cellular networks.
AB  - Since being discovered and intensively studied for over a decade, Smad
      ubiquitylation regulatory factor-1 (Smurf1) has been linked with several
      important biological pathways, including the bone morphogenetic protein pathway,
      the non-canonical Wnt pathway, and the mitogen-activated protein kinase pathway.
      Multiple functions of this ubiquitin ligase have been discovered in cell growth
      and morphogenesis, cell migration, cell polarity, and autophagy. Smurf1 is
      related to physiological manifestations in terms of age-dependent deficiency in
      bone formation and invasion of tumor cells. Smurf1-knockout mice have a
      significant phenotype in the skeletal system and considerable manifestations
      during embryonic development and neural outgrowth. In depth studying of Smurf1
      will help us to understand the etiopathological mechanisms of related disorders.
      Here, we will summarize historical and recent studies on Smurf1, and discuss the
      E3 ligase-dependent and -independent functions of Smurf1. Moreover, intracellular
      regulations of Smurf1 and related physiological phenotypes will be described in
      this review.

PMID- 23007850
TI  - Exploring connections between moderators and mediators: commentary on subgroup
      analyses in intervention research.
AB  - Although subgroup analyses, and moderator analyses more generally, in
      intervention research are fraught with analytic and conceptual challenges, they
      provide invaluable insights into the effectiveness of intervention strategies and
      the theoretical models upon which they rest. The papers in this Special Issue
      engage these challenges and offer investigators a set of strategies that will
      enhance how they think about, measure, test, and report evidence of moderated
      intervention effects. In this commentary, I echo the call for more thoughtful
      work on moderated intervention effects and, in particular, urge investigators to
      pursue opportunities to integrate questions regarding mediation as they work to
      specify how intervention strategies operate across populations, settings, and
      behavioral domains.

PMID- 23007851
TI  - A phenolic derivative and two diacetylenes from Symphyotrichum subulatum.
AB  - A pytochemical study on the constituents of the roots of Symphyotrichum subulatum
      led to the isolation of three new compounds including two diacetylenes, asterynes
      A (1) and B (2), and (E)-4-(3-acetoxyprop-1-enyl)-2-methoxyphenyl (S)-2
      methylbutanoate (3) along with twelve known compounds. Their structures were
      elucidated with spectroscopic analyses. Compound 3 showed anti-inflammatory
      activity on LPS-induced NO production with an EC50 value of 15.0 uM.

PMID- 23007853
TI  - Real people, real stories: a new mass media campaign that could help smokers
      quit.

PMID- 23007852
TI  - New phenolic compounds with anti-adipogenic activity from the aerial parts of
      Pulsatilla koreana.
AB  - Three new phenolic compounds, pulsatillosides A (1), B (2), and C (3), were
      isolated from the aerial parts of Pulsatilla koreana, together with two known
      flavonoid glycosides, trans-tiliroside (4) and kaempferol-3-O-beta-glycoside (5).
      The structures of the isolated compounds were determined on the basis of
      spectroscopic analysis including 1D, 2D NMR and HR-MS. Among the isolated
      compounds, compounds 1-3 significantly inhibited adipocyte differentiation as
      measured by fat accumulation in 3 T3-L1 cells using Oil Red O staining.

PMID- 23007854
TI  - The impact of receiving treatment for cancer at a large metropolitan teaching
      hospital as recorded by patients using unstructured journals.
AB  - The aim was to obtain patients' experiences of the cancer treatment pathway at a
      tertiary teaching hospital using unstructured journals to enable health care
      professionals to be educated on how to improve patient care. Most of 38 patients
      (22 females and 16 males), average age of 58 (range 29-80), who returned diaries
      were starting chemotherapy for a range of cancers. Data entries were transcribed
      and entered into the NVIVO software to facilitate thematic analysis. Women wrote
      more, and more often than men, and disclosed more. For most, physical side
      effects dominated, comprising 25-75 % of diary entries. The most commonly
      mentioned were fatigue (74 %), pain (63 %), sleep disturbances (50 %), nausea (45
      %) and changes in appetite (45 %). Collectively, 22 patients reported 261
      separate emotional reactions including depression, anger, guilt, shame, grief,
      panic and confusion. The treatment environment, including personnel, impacted
      upon patients. Where survival is unpredictable, evidence of consistency of
      practitioners' approaches attains heightened significance.

PMID- 23007855
TI  - Information needs of cancer patients: a comparison of nurses' and patients'
      perceptions.
AB  - This study aimed to identify nurses' and patients' perceptions and compare them
      in terms of the information needs of cancer patients. Another aim is to identify
      the association between the demographic and situational characteristics of
      patients'/nurses' and information needs. A total of 305 patients and 130 nurses
      participated in this descriptive and comparative study. Data was collected with a
      study-specific questionnaire developed for this study. Descriptive statistics,
      Pearson Chi-square and RIDIT analyses were used to analyze the data. Results
      indicated that there was incongruence between patients' and nurses' perceptions
      regarding information provision (p < 0.05), both congruence regarding how much
      information was needed (eight out of 16 information items), but also significant
      incongruence on the remaining items(p < 0.05). The other finding was that
      patients residing out of Ankara city needed to obtain more information rather
      than the others. No relationship was found between demographic and situational
      characteristics and nurses' perceptions regarding information need of patients.

PMID- 23007856
TI  - Gene expression associated with apogamy commitment in Ceratopteris richardii.
AB  - Apogamy is a phenomenon in which a sporophyte develops asexually, directly from a
      cell or cells of a gametophyte. It is a phenomenon described mainly in lower
      plants, but shares certain aspects with apomixis in angiosperms. The genes
      involved in apogamy commitment in ferns are unknown. We hypothesize that the
      mechanism of asexual reproduction is controlled in lower and higher plants by
      overlapping sets of genes. To this end, we created a normalized subtracted cDNA
      library that represents genes with increased expression during apogamy commitment
      in the fern Ceratopteris richardii. The cDNA library consists of 170 unique
      sequences. Compared to the mature gametophyte transcriptome of the fern Pteridium
      aquilinum, the apogamy library is enriched in plant GO-Slim terms that are
      associated with stress and metabolism. In silico expression analyses of the
      closest Arabidopsis homologs of the apogamy library revealed many genes that
      display preferential expression in seed and flower tissues, structures that are
      absent in ferns. This apogamy library provides a rich resource for investigations
      into the genetic control of apogamy in ferns and comparisons with the asexual
      processes of higher plants.

PMID- 23007857
TI  - Chelating Schiff base assisted azide-bridged Mn(II), Ni(II) and Cu(II) magnetic
      coordination polymers.
AB  - Four new Mn(II), Ni(II) and Cu(II) coordination polymers [Mn2(L1)(MU(1,1)
      N3)2(MU(1,3)-N3)2]n (1), [Ni(L2)2(MU(1,3)-N3)]n(ClO4)n (2), [Cu(L3)(MU(1,1)
      N3)(N3)]n (3) and [Cu(L4)(MU(1,1)-N3)2]n (4) (L1 = N,N'-bis(2
      pyridylmethylene)ethane-1,2-diamine, L2 = N-(2-pyridylmethylene)methylamine, L3 =
      N-(2-pyridylmethylene)-3-pyridylamine, L4 = N-(2-pyridylmethylene)-tbutylamine)
      have been synthesized and characterized by single-crystal X-ray analysis and
      magnetic measurements. Complex 1 indicates a stoichiometry-dependent structural
      change (based on Mn:L1:N3 = 2:1:4 molar ratio) and consists of two-dimensional (2
      D) (4,4) net layers, in which Mn(II) centers are co-bridged by single end-to-end
      (EE), double end-on (EO) azide and chelate-bridging L1 ligands. Complex 2 shows a
      single EE azide-bridged one-dimensional (1-D) Ni(II) chain. Complexes 3 and 4
      indicate single EO and double EO azide-bridged 1-D Cu(II) chains, respectively.
      Complex 1 exhibits weak ferromagnetism due to its intra-layer spin-canting with
      T(c) = 20 K. Complex 2 shows an unusual intra-chain ferromagnetic coupling and
      spin-canting behaviour. Both complexes 3 and 4 exhibit intra-chain
      antiferromagnetic interactions. Magneto-structural parameters for these related
      complexes were also discussed.

PMID- 23007858
TI  - Comparison of 3D computer-aided with manual cerebral aneurysm measurements in
      different imaging modalities.
AB  - INTRODUCTION: To compare intra- and inter-observer reliability of aneurysm
      measurements obtained by a 3D computer-aided technique with standard manual
      aneurysm measurements in different imaging modalities. METHODS: A total of 21
      patients with 29 cerebral aneurysms were studied. All patients underwent digital
      subtraction angiography (DSA), contrast-enhanced (CE-MRA) and time-of-flight
      magnetic resonance angiography (TOF-MRA). Aneurysm neck and depth diameters were
      manually measured by two observers in each modality. Additionally, semi-automatic
      computer-aided diameter measurements were performed using 3D vessel surface
      models derived from CE- (CE-com) and TOF-MRA (TOF-com) datasets. Bland-Altman
      analysis (BA) and intra-class correlation coefficient (ICC) were used to evaluate
      intra- and inter-observer agreement. RESULTS: BA revealed the narrowest relative
      limits of intra- and inter-observer agreement for aneurysm neck and depth
      diameters obtained by TOF-com (ranging between +/-5.3 % and +/-28.3 %) and CE-com
      (ranging between +/-23.3 % and +/-38.1 %). Direct measurements in DSA, TOF-MRA
      and CE-MRA showed considerably wider limits of agreement. The highest ICCs were
      observed for TOF-com and CE-com (ICC values, 0.92 or higher for intra- as well as
      inter-observer reliability). CONCLUSION: Computer-aided aneurysm measurement in
      3D offers improved intra- and inter-observer reliability and a reproducible
      parameter extraction, which may be used in clinical routine and as objective
      surrogate end-points in clinical trials.

PMID- 23007859
TI  - Depression and risk of transformation of episodic to chronic migraine.
AB  - The aim of this study was to assess the role of depression as a predictor of new
      onset of chronic migraine (CM) among persons with episodic migraine (EM). The
      American Migraine Prevalence and Prevention (AMPP) study followed 24,000 persons
      with severe headache identified in 2004. Using random-effects logistic
      regression, we modeled the probability that persons with EM in 2005 or 2006 would
      develop CM in the subsequent year. Depression was assessed in two ways, using a
      validated questionnaire (PHQ-9 score >=15) and based on self-reported medical
      diagnosis. Analyses were adjusted for multiple covariates including
      sociodemographics, body mass index, headache pain intensity, headache frequency,
      migraine symptom severity, cutaneous allodynia, acute medication overuse, anti
      depressant use and anxiety. Of 6,657 participants with EM in 2005, 160 (2.4 %)
      developed CM in 2006. Of 6,852 participants with EM in 2006, 144 (2.2 %)
      developed CM in 2007. In fully adjusted models, PHQ-9 defined depression was a
      significant predictor of CM onset [odds ratio (OR) = 1.65, 95 % CI 1.12-2.45].
      There was a depression-dose effect; relative to participants with no depression
      or mild depression, those with moderate (OR = 1.77, 95 % CI 1.25-2.52),
      moderately severe (OR = 2.35, 95 % CI 1.53-3.62), and severe depression (OR =
      2.53, 95 % CI 1.52-4.21) were at increased risk for the onset of CM. Among
      persons with EM, depression was associated with an increased risk of CM after
      adjusting for sociodemographic variables and headache characteristics. Depression
      preceded the onset of CM and risk increased with depression severity suggesting a
      potentially causal role though reverse causality cannot be excluded.

PMID- 23007860
TI  - Transcriptome and small RNA deep sequencing reveals deregulation of miRNA
      biogenesis in human glioma.
AB  - Altered expression of oncogenic and tumour-suppressing microRNAs (miRNAs) is
      widely associated with tumourigenesis. However, the regulatory mechanisms
      underlying these alterations are poorly understood. We sought to shed light on
      the deregulation of miRNA biogenesis promoting the aberrant miRNA expression
      profiles identified in these tumours. Using sequencing technology to perform both
      whole-transcriptome and small RNA sequencing of glioma patient samples, we
      examined precursor and mature miRNAs to directly evaluate the miRNA maturation
      process, and examined expression profiles for genes involved in the major steps
      of miRNA biogenesis. We found that ratios of mature to precursor forms of a large
      number of miRNAs increased with the progression from normal brain to low-grade
      and then to high-grade gliomas. The expression levels of genes involved in each
      of the three major steps of miRNA biogenesis (nuclear processing, nucleo
      cytoplasmic transport, and cytoplasmic processing) were systematically altered in
      glioma tissues. Survival analysis of an independent data set demonstrated that
      the alteration of genes involved in miRNA maturation correlates with survival in
      glioma patients. Direct quantification of miRNA maturation with deep sequencing
      demonstrated that deregulation of the miRNA biogenesis pathway is a hallmark for
      glioma genesis and progression.

PMID- 23007861
TI  - APC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the
      mitotic checkpoint complex.
AB  - The anaphase-promoting complex/cyclosome (APC/C) bound to CDC20 (APC/C(CDC20))
      initiates anaphase by ubiquitylating B-type cyclins and securin. During
      chromosome bi-orientation, CDC20 assembles with MAD2, BUBR1 and BUB3 into a
      mitotic checkpoint complex (MCC) that inhibits substrate recruitment to the
      APC/C. APC/C activation depends on MCC disassembly, which was proposed to require
      CDC20 autoubiquitylation. Here we characterize APC15, a human APC/C subunit
      related to yeast Mnd2. APC15 is located near APC/C's MCC binding site; it is
      required for APC/C-bound MCC (APC/C(MCC))-dependent CDC20 autoubiquitylation and
      degradation and for timely anaphase initiation but is dispensable for substrate
      ubiquitylation by APC/C(CDC20) and APC/C(CDH1). Our results support the model
      wherein MCC is continuously assembled and disassembled to enable rapid activation
      of APC/C(CDC20) and CDC20 autoubiquitylation promotes MCC disassembly. We propose
      that APC15 and Mnd2 negatively regulate APC/C coactivators and report generation
      of recombinant human APC/C.

PMID- 23007863
TI  - Investigation of post-grafted groups of a porous coordination polymer and its
      proton conduction behavior.
AB  - We investigated the configuration of substituent groups that are post
      synthetically bound to the pore surface in a porous coordination polymer. This
      study demonstrates the observations of orientation and coordination fashions of
      the grafted groups, which contribute towards improved proton conductivity in
      porous frameworks.

PMID- 23007862
TI  - Performing vaginal lavage, crystal violet staining, and vaginal cytological
      evaluation for mouse estrous cycle staging identification.
AB  - A rapid means of assessing reproductive status in rodents is useful not only in
      the study of reproductive dysfunction but is also required for the production of
      new mouse models of disease and investigations into the hormonal regulation of
      tissue degeneration (or regeneration) following pathological challenge. The
      murine reproductive (or estrous) cycle is divided into 4 stages: proestrus,
      estrus, metestrus, and diestrus. Defined fluctuations in circulating levels of
      the ovarian steroids 17-beta-estradiol and progesterone, the gonadotropins
      luteinizing and follicle stimulating hormones, and the luteotropic hormone
      prolactin signal transition through these reproductive stages. Changes in cell
      typology within the murine vaginal canal reflect these underlying endocrine
      events. Daily assessment of the relative ratio of nucleated epithelial cells,
      cornified squamous epithelial cells, and leukocytes present in vaginal smears can
      be used to identify murine estrous stages. The degree of invasiveness, however,
      employed in collecting these samples can alter reproductive status and elicit an
      inflammatory response that can confound cytological assessment of smears. Here,
      we describe a simple, non-invasive protocol that can be used to determine the
      stage of the estrous cycle of a female mouse without altering her reproductive
      cycle. We detail how to differentiate between the four stages of the estrous
      cycle by collection and analysis of predominant cell typology in vaginal smears
      and we show how these changes can be interpreted with respect to endocrine
      status.

PMID- 23007864
TI  - Enhanced adsorption of Eu(III) on mesoporous Al2O3/expanded graphite composites
      investigated by macroscopic and microscopic techniques.
AB  - Mesoporous Al(2)O(3) was intercalated into an expanded graphite (EG) interlayer
      to prepare mesoporous Al(2)O(3)/EG composites. The basal spacing of mesoporous
      Al(2)O(3)/EG composites was enlarged as compared to raw graphite from the X-ray
      diffraction analysis. The massive surface functional groups and wedge-shaped
      pores were observed in terms of potentiometric acid-base titration analysis and
      scanning electron microscope, respectively. The pH-dependent adsorption of
      Eu(III) on mesoporous Al(2)O(3)/EG composites was evidently independent of ionic
      strength. The maximum adsorption capacity of Eu(III) on mesoporous Al(2)O(3)/EG
      composites at pH 6.0 and T = 293 K was calculated to be 5.14 mg g(-1). Desorption
      kinetics and cyclic operation results showed that mesoporous Al(2)O(3)/EG
      composites presented high hydrothermal stability in aqueous solution. The
      thermodynamic parameters suggested that Eu(III) adsorption on mesoporous
      Al(2)O(3)/EG composites is an endothermic and a spontaneous process. The decrease
      of Eu-O bond distance with the increasing pH demonstrated that the adsorption
      mechanism between Eu(III) and mesoporous Al(2)O(3)/EG composites would shift from
      outer-sphere surface complexation to inner-sphere surface complexation in terms
      of extended X-ray absorption fine structure spectroscopy analysis.

PMID- 23007866
TI  - Sleep apnoea in syndromic craniosynostosis occurs independent of hindbrain
      herniation.
AB  - PURPOSE: Hindbrain herniation (HH) is frequently found in syndromic
      craniosynostosis. It may cause impairment of the respiratory centres and manifest
      as sleep-disordered breathing. Our aim was to quantify sleep apnoea caused by HH
      in children with syndromic craniosynostosis. METHODS: Seventy-one children with
      syndromic and complex craniosynostosis (aged 0-18 years) underwent prospective
      magnetic resonance imaging and a sleep study. The position of the cerebellar
      tonsils and respiratory parameters were evaluated and analysed. None of the
      included patients had undergone previous foramen magnum decompression. RESULTS:
      HH was present in 35% of the patients and was more frequent in children with
      Crouzon syndrome (63%) than in other types of craniosynostosis (p = .018). There
      was a positive association between the position of the cerebellar tonsils and
      papilledema (p = .002). Sleep studies of children with craniosynostosis and HH
      were not different from those without HH. Obstructive sleep apnoea syndrome was
      not more prevalent in children with HH compared to those without HH (p = .12). A
      cluster analysis using indices of apnoea revealed that three new clusters between
      which age was significantly different (p = .025). CONCLUSION: Sleep apnoea in
      syndromic craniosynostosis is not caused by HH. Rather, our evidence suggests
      that sleep-disordered breathing in craniosynostosis may be caused by brain stem
      immaturity in young children or upper airway obstruction. Therefore, as long as
      the child remains asymptomatic, our preferred management of HH is to be
      conservative and provide regular neurosurgical follow-up.

PMID- 23007867
TI  - Breast cancer among shift workers: results of the WOLF longitudinal cohort study.
AB  - OBJECTIVE: The aim of this study was to investigate whether shift work (with or
      without night work) is associated with increased risk of breast cancer. METHODS:
      The population consisted of 4036 women. Data were obtained from WOLF (Work,
      Lipids, and Fibrinogen), a longitudinal cohort study. Information about baseline
      characteristics was based on questionnaire responses and medical examination.
      Cancer incidence from baseline to follow-up was obtained from the national cancer
      registry. Two exposure groups were identified: shift work with and without night
      work. The group with day work only was used as the reference group in the
      analysis. Cox regression analysis was used to calculate relative risk. RESULTS:
      In total, 94 women developed breast cancer during follow-up. The average follow
      up time was 12.4 years. The hazard ratio for breast cancer was 1.23 [95%
      confidence interval (95% CI) 0.70-2.17] for shifts without night work and 2.02
      (95% CI 1.03-3.95) for shifts with night work. When including only women <60
      years of age, the risk estimates were 1.18 (95% CI 0.67-2.07) for shifts without
      night work, and 2.15 (95% CI 1.10-4.21) for shifts with night work. CONCLUSIONS:
      Our results indicate an increased risk for breast cancer among women who work
      shifts that includes night work.

PMID- 23007869
TI  - Nursing research in stress, psychoneuroimmunology, and allostasis.

PMID- 23007868
TI  - Self-recognition of high-mannose type glycans mediating adhesion of embryonal
      fibroblasts.
AB  - High-mannose type N-linked glycan with 6 mannosyl residues, termed "M6Gn2",
      displayed clear binding to the same M6Gn2, conjugated with ceramide mimetic (cer
      m) and incorporated in liposome, or coated on polystyrene plates. However, the
      conjugate of M6Gn2-cer-m did not interact with complex-type N-linked glycan with
      various structures having multiple GlcNAc termini, conjugated with cer-m. The
      following observations indicate that hamster embryonic fibroblast NIL-2 K cells
      display homotypic autoadhesion, mediated through the self-recognition capability
      of high-mannose type glycans expressed on these cells: (i) NIL-2 K cells display
      clear binding to lectins capable of binding to high-mannose type glycans (e.g.,
      ConA), but not to other lectins capable of binding to other carbohydrates (e.g.
      GS-II). (ii) NIL-2 K cells adhere strongly to plates coated with M6Gn2-cer-m, but
      not to plates coated with complex-type N-linked glycans having multiple GlcNAc
      termini, conjugated with cer-m; (iii) degree of NIL-2 K cell adhesion to plates
      coated with M6Gn2-cer-m showed a clear dose-dependence on the amount of M6Gn2-cer
      m; and (iv) the degree of NIL-2 K adhesion to plates coated with M6Gn2-cer-m was
      inhibited in a dose-dependent manner by alpha1,4-L-mannonolactone, the specific
      inhibitor in high-mannose type glycans addition. These data indicate that
      adhesion of NIL-2 K is mediated by self-aggregation of high mannose type glycan.
      Further studies are to be addressed on auto-adhesion of other types of cells
      based on self interaction of high mannose type glycans.

PMID- 23007870
TI  - A systematic review of allostatic load, health, and health disparities.
AB  - The theoretical constructs of allostasis and allostatic load (AL) have
      contributed to our understanding of how constantly changing social and
      environmental factors impact physiological functioning and shape health and aging
      disparities, particularly along socioeconomic, gendered, racial, and ethnic
      lines. AL represents the cumulative dysregulation of biological systems with
      prolonged or poorly regulated allostatic responses. Nearly two decades of
      empirical research has focused on operationalizing the AL construct for examining
      the antecedents and health outcomes accompanying multisystem biological
      dysregulation. The purpose of this systematic review is to examine the empirical
      literature that quantifies the AL construct; the review also evaluates the
      social, environmental, and genetic antecedents of AL as well as its predictive
      utility for a variety of health outcomes. A total of 58 articles published
      between 1997 and 2012 were retrieved, analyzed, and synthesized. The results
      revealed considerable heterogeneity in the operationalization of AL and the
      measurement of AL biomarkers, making interpretations and comparisons across
      studies challenging. There is, however, empirical substantiation for the
      relationships between AL and socioeconomic status, social relationships,
      workplace, lifestyle, race/ethnicity, gender, stress exposure, and genetic
      factors. The literature also demonstrated associations between AL and physical
      and mental health and all-cause mortality. Targeting the antecedents of AL during
      key developmental periods is essential for improving public health. Priorities
      for future research include conducting prospective longitudinal studies,
      examining a broad range of antecedent allostatic challenges, and collecting
      reliable measures of multisystem dysregulation explicitly designed to assess AL,
      at multiple time points, in population-representative samples.

PMID- 23007871
TI  - Stress and gene expression of individuals with chronic abdominal pain.
AB  - BACKGROUND: Research examining the role of stress in gastrointestinal (GI)
      symptoms such as chronic abdominal pain (CAP) is controversial. The purpose of
      this study was to examine the expression of genes involved in metabolic stress
      and toxicity in men and women with high and low levels of perceived stress with
      and without CAP. METHODS: Data and samples were collected and the expression of
      genes involved in metabolic stress and toxicity was analyzed in 26 individuals
      who had consented to participate in a natural history protocol. Subjects
      completed the 10-item Perceived Stress scale (PSS). Fasting participants'
      peripheral whole blood was collected for proteomic and genomic studies.
      Polymerase chain reaction (PCR) array was used to analyze the expression of 84
      key genes involved in human stress and toxicity plus 5 housekeeping genes. Plasma
      interleukin-1 alpha (IL-1alpha) protein was quantified via enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Interleukin-1 alpha gene (IL1A) was
      upregulated in females with high stress versus females with low stress by 2.58
      fold (95% CI [0.88, 4.28]). IL1A was upregulated in participants with high stress
      and CAP versus those with low stress and CAP by 3.47-fold (95% CI [1.14, 5.80]).
      CONCLUSIONS: An upregulation of the gene coding the pro-inflammatory cytokine IL
      1alpha suggests that the mechanism behind stress-related changes in GI symptoms
      is pro-inflammatory in nature. The results of this study contribute to the
      knowledge of the mechanism behind stress-related CAP symptoms and gender
      differences associated with these disorders.

PMID- 23007872
TI  - Effect of diphlorethohydroxycarmalol isolated from Ishige okamurae on apoptosis
      in 3 T3-L1 preadipocytes.
AB  - Obesity is an important issue in the world of public health and preventive
      medicine. Inhibition of proliferation of preadipocytes plays an important role in
      proposed antiobesity mechanisms. In this study, we investigated the effect of
      diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae on the apoptotic
      pathway. The results showed that DPHC inhibited population growth in 3 T3-L1
      preadipocytes as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Flow cytometric analysis of 3 T3-L1
      preadipocytes showed that the number of early and late apoptotic cells increases
      in a dose-dependent manner after exposure to DPHC, while the number of normal
      cells was reduced. Our findings indicate that the induction of apoptosis in 3 T3
      L1 preadipocytes by DPHC is mediated through the activation of caspase-3, Bax,
      and caspase-9, and then through the cleavage of poly(ADP-ribose) polymerase and
      the down-regulation of Bcl-2. The data also indicated that treatment with DPHC
      inhibits histone deacetylase activity in 3 T3-L1 preadipocytes. These results
      show that DPHC efficiently induces apoptosis in 3 T3-L1 preadipocytes.

PMID- 23007873
TI  - Global and local indices for characterizing biomolecular flexibility and
      rigidity.
AB  - Understanding flexibility and rigidity characteristics of biomolecules is a
      prerequisite for understanding biomolecular structural stability and function.
      Computational methods have been implemented that directly characterize
      biomolecular flexibility and rigidity by constraint network analysis. For
      deriving maximal advantage from these analyses, their results need to be linked
      to biologically relevant characteristics of a structure. Such links are provided
      by global and local measures ("indices") of biomolecular flexibility and
      rigidity. To date, more than 14 indices are available with sometimes overlapping
      or only vague definitions. We present concise definitions of these indices,
      analyze the relation between, and the scope and limitations of them, and compare
      their informative value. For this, we probe the structural stability of the
      calcium binding protein alpha-lactalbumin as a showcase, both in the "ground
      state" and after perturbing the system by changing the network topology. In
      addition, we introduce three indices for the first time that extend the
      application domain of flexibility and rigidity analyses. The results allow us to
      provide guidelines for future studies suggesting which of these indices could
      best be used for analyzing, understanding, and quantifying structural features
      that are important for biomolecular stability and function. Finally, we make
      suggestions for proper index notations in future studies to prevent the
      misinterpretation and to facilitate the comparison of results obtained from
      flexibility and rigidity analyses.

PMID- 23007874
TI  - Characteristics of predrinking and associated risks: a survey in a sample of
      German high school students.
AB  - OBJECTIVES: Finding predictors for predrinking and placing the new phenomenon of
      predrinking on a greater database. Predrinking is defined as alcohol consumption,
      alone or with friends, at home or at public places, before going out in the
      evening to a party or in bars or discotheques. METHODS: Data were collected from
      a representative sample of 757 ninth- and tenth-grade students from 31 high
      schools located in a south German rural region and a city. RESULTS: Predrinkers,
      especially those who show this behaviour frequently, were notably more likely to
      engage in hazardous drinking, and experienced significantly more frequent
      involvements in fights and alcohol-induced blackouts. They also stated more often
      that they had the intention of getting drunk when consuming alcohol. CONCLUSIONS:
      Predrinking proves to be a high-risk behaviour, particularly when it occurs at a
      high frequency. This behaviour has to be seen as part of a new youth culture,
      which does not seem to be limited to a certain subgroup-with all of the
      associated risks.

PMID- 23007875
TI  - The age-dependent influence of self-reported health and job characteristics on
      retirement.
AB  - OBJECTIVES: Social scientists and economists doubt the usefulness of self
      reported health status as an indicator of overall health status. Self-reported
      health acts as a justification for retirement when this decision is in reality
      driven by other reasons. In this study, we looked at income, job satisfaction,
      and job status. METHODS: We introduce a survival model (Cox model) that
      simultaneously includes both health and job characteristics as independent
      variables. We also take the age-dependent character of these effects into
      account. RESULTS: An analysis of the European Community Household Panel data did
      not validate the justification bias with respect to these variables. The addition
      of job characteristics had no influence on the effect estimates of self-reported
      health. CONCLUSIONS: We found significant effects for self-reported health as
      well as for objective health measures. The addition of job characteristics did
      not contribute to the explanation of the effect of self-reported health
      falsifying the justification bias hypothesis.

PMID- 23007876
TI  - Bluetongue virus - 23 stimulates inducible nitric oxide synthase expression and
      nitric oxide production in mononuclear cells of blood and/or regional lymphoid
      organs.
AB  - Mononuclear leukocytes of peripheral blood mononuclear cells (PBMCs) and regional
      lymphoid organs (RLOs) play a critical role in primary BTV replication and
      subsequent viral dissemination to distant systemic organs. The lesions in animals
      develop primarily as a result of vascular insult, presumably induced by the
      activity of viral and/or proinflammatory vasoactive mediators. Hence, the current
      study was designed in sheep to investigate the responses of potent
      vasoactivators, inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO)
      in mononuclear leukocytes of PBMCs and RLOs. The results show that BTV infection
      of sheep led to enhanced transcription of iNOS in PBMCs and in particular RLOs.
      The BTV RNAs and/or antigens were readily demonstrable in these mononuclear
      leukocytes, suggesting the possible role of BTV in iNOS induction. Moreover, upon
      in vitro infection of PBMCs with BTV-23, iNOS was up-regulated in time-dependent
      fashion and correlated with increased NO production. The results from these in
      vivo and in vitro studies thus suggest iNOS and NO produced by mononuclear
      leukocytes may potentially contribute to vascular-related pathology of BT.

PMID- 23007877
TI  - Profiling of virulence associated genes of Pasteurella multocida isolated from
      cattle.
AB  - Pasteurella multocida is a causative agent of many major diseases of which
      haemorrhagic septiciemia (HS) in cattle & a buffalo is responsible for
      significant losses to livestock sector in India and south Asia. The disease
      outcome is affected by various host- and pathogen-specific determinants. Several
      bacterial species-specific putative virulence factors including the capsular and
      virulence associated genes have been proposed to play a key role in this
      interaction. A total of 23 isolates of P. multocida were obtained from 335 cases
      of various clinically healthy and diseased cattle. These isolates were examined
      for capsule synthesis genes (capA, B, D, E and F) and eleven virulence associated
      genes (tbpA, pfhA, toxA, hgbB, hgbA, nanH, nanB, sodA, sodC, oma87 and ptfA) by
      PCR. A total of 19 P. multocida isolates belonging to capsular type B and 4 of
      capsular type A were isolated. All isolates of capsular type B harboured the
      virulence associated genes: tbpA, pfhA, hgbA, sodC and nanH, coding for
      transferrin binding protein, filamentous hemagglutinin, haemoglobin binding
      protein, superoxide dismutase and neuraminidases, respectively; while isolates
      belonging to capsular type A also carried tbpA, pfhA, hgbA and nanH genes. Only
      50 % of capsular type A isolates contained sodC gene while 100 % of capsular type
      B isolates had sodC gene. The gene nanB and toxA were absent in all the 23
      isolates. In capsular type A isolates, either sodA or sodC gene was present &
      these genes did not occur concurrently. The presence of virulence associated gene
      ptfA revealed a positive association with the disease outcome in cattle and could
      therefore be an important epidemiological marker gene for characterizing P.
      multocida isolates.

PMID- 23007878
TI  - Biglycan expression and clinical outcome in patients with pancreatic
      adenocarcinoma.
AB  - Conflicting results have been reported on the role of extracellular matrix (ECM)
      proteins in pancreatic cancer. Preclinical studies suggest that the
      overexpression of biglycan (proteoglycan-I, PG-I), a leucine-rich protein of the
      ECM, may induce growth arrest of pancreatic cancer cells. The aim of this study
      was to assess the prognostic role of biglycan expression in pancreatic cancer. We
      also evaluated MIB-1 and COX-2 expressions (as potential markers of growth and
      aggressiveness) to better characterize the biology of the tumors. The classical
      pathological parameters (grading, desmoplasia, perineural, or vascular invasion)
      as well as molecular determinants of prognosis were examined. MIB-1 (a
      proliferative index associated with prognosis in most tumors), COX-2, and PG-I
      expressions were detected by immunohistochemistry and immunofluorescence on
      tissue samples from 53 patients with pancreatic cancer and reviewed by two
      independent pathologists. To verify PG-I expression, three rabbit sera (LF104,
      LF112, and LF121 from NIH, Bethesda, MA, US) were tested. Logrank test and Cox's
      model were applied for statistical analysis. Out of 53 patients, 40 had stage III
      and IV pancreatic cancer. Fourteen patients did not express any of the PG-I
      epitopes. The patients who expressed at least two PG-I epitopes had shorter
      survival compared to those with single epitope or lacking any expression (28 vs
      44 weeks, P = 0.0021). The MIB-1 higher expression predicted shorter survival (25
      vs 41 weeks, P = 0.0059). The other parameters were not associated with clinical
      outcome. Multivariate analyses confirmed PG-I expression and MIB-1 as independent
      negative prognostic factors. Patients who presented PG-I expression in the ECM
      had the worse prognosis compared to those who did not. Our results are not in
      contrast with the hypothesis that ECM proteins are a potential barrier to
      metastatic spread in localized pancreatic cancer. Rather, we underline the
      complexity of tumor-stroma interactions in the advanced stage of cancer and the
      need of further study.

PMID- 23007879
TI  - A novel blueprint for 'top down' differentiation defines the cervical
      squamocolumnar junction during development, reproductive life, and neoplasia.
AB  - The cervical squamocolumnar (SC) junction is the site of a recently discovered
      'embryonic' cell population that was proposed as the cell of origin for cervical
      cancer and its precursors. How this population participates in cervical
      remodelling and neoplasia is unclear. In the present study, we analysed the SC
      junction immunophenotype during pre- and post-natal human and mouse development
      and in the adult, processes of metaplastic evolution of the SC junction,
      microglandular change, and early cervical neoplasia. Early in life, embryonic
      cervical epithelial cells were seen throughout the cervix and subsequently
      diminished in number to become concentrated at the SC junction in the adult. In
      all settings, there was a repetitive scenario in which cuboidal embryonic/SC
      junction cells gave rise to subjacent metaplastic basal/reserve cells with a
      switch from the SC junction positive to negative immunophenotype. This downward
      or basal (rather than upward or apical) evolution from progenitor cell to
      metaplastic progeny was termed reverse or 'top down' differentiation. A similar
      pattern was noted in high-grade squamous intraepithelial lesions (HSILs),
      suggesting that HPV infection of the cuboidal SC junction cells initiated
      outgrowth of basally-oriented neoplastic progeny. The progressive loss of the
      embryonic/SC junction markers occurred with 'top down' differentiation during
      development, remodelling, and early neoplasia. Interestingly, most low-grade SILs
      were SC junction-negative, implying infection of metaplastic progeny rather than
      the original SC junction cells. This proposed model of 'top down' differentiation
      resolves the mystery of how SC junction cells both remodel the cervix and
      participate in neoplasia and provides for a second population of metaplastic
      progeny (including basal and reserve cells), the infection of which is
      paradoxically less likely to produce a biologically aggressive precursor. It also
      provides new targets in animal models to determine why the SC junction is
      uniquely susceptible to carcinogenic HPV infection.

PMID- 23007880
TI  - Role of 1 week of antibiotic prophylaxis before percutaneous nephrolithotomy.

PMID- 23007881
TI  - Behavioral counseling after screening for alcohol misuse in primary care: a
      systematic review and meta-analysis for the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Alcohol misuse, which includes the full spectrum from risky drinking
      to alcohol dependence, is a leading cause of preventable death in the United
      States. PURPOSE: To evaluate the benefits and harms of behavioral counseling
      interventions for adolescents and adults who misuse alcohol. DATA SOURCES:
      MEDLINE, EMBASE, the Cochrane Library, CINAHL, PsycINFO, International
      Pharmaceutical Abstracts, and reference lists of published literature (January
      1985 through January 2012, limited to English-language articles). STUDY
      SELECTION: Controlled trials at least 6 months' duration that enrolled persons
      with alcohol misuse identified by screening in primary care settings and
      evaluated behavioral counseling interventions. DATA EXTRACTION: One reviewer
      extracted data and a second checked accuracy. Two independent reviewers assigned
      quality ratings and graded the strength of the evidence. DATA SYNTHESIS: The 23
      included trials generally excluded persons with alcohol dependence. The best
      evidence was for brief (10- to 15-minute) multicontact interventions. Among
      adults receiving behavioral interventions, consumption decreased by 3.6 drinks
      per week from baseline (weighted mean difference, 3.6 drinks/wk [95% CI, 2.4 to
      4.8 drinks/wk]; 10 trials; 4332 participants), 12% fewer adults reported heavy
      drinking episodes (risk difference, 0.12 [CI, 0.07 to 0.16]; 7 trials; 2737
      participants), and 11% more adults reported drinking less than the recommended
      limits (risk difference, 0.11 [CI, 0.08 to 0.13]; 9 trials; 5973 participants)
      over 12 months compared with control participants (moderate strength of
      evidence). Evidence was insufficient to draw conclusions about accidents,
      injuries, or alcohol-related liver problems. Trials enrolling young adults or
      college students showed reduced consumption and fewer heavy drinking episodes
      (moderate strength of evidence). Little or no evidence of harms was found.
      LIMITATIONS: Results may be biased to the null because the behavior of control
      participants could have been affected by alcohol misuse assessments. In addition,
      evidence is probably inapplicable to persons with alcohol dependence and
      selective reporting may have occurred. CONCLUSION: Behavioral counseling
      interventions improve behavioral outcomes for adults with risky drinking. PRIMARY
      FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 23007882
TI  - Antibiotic sensitivity of bacteria on the oral mucosa after hematopoietic cell
      transplantation.

PMID- 23007883
TI  - Evaluation of a patient information website for childhood cancer survivors.
AB  - PURPOSE: Childhood cancer survivors (CCS) are in need of specialized information
      about late effects of treatment. In the current study, we assessed the perceived
      usability and satisfaction with the content of a national website with
      information on late effects and analyzed possible determinants related to website
      usability and content satisfaction. METHODS: CCS and their parents were contacted
      through our local follow-up program and via online media to complete an online
      questionnaire regarding their baseline characteristics, medical decision style,
      and the usability and content of the website. Usability was evaluated using the
      System Usability Scale (SUS), a validated questionnaire resulting in a score from
      0 to 100. For the content rating, we constructed a six-item scale resulting in a
      score from 1 to 5 (Cronbach's alpha, 0.83). Comments were analyzed qualitatively.
      RESULTS: Fifty-five survivors and forty-three parents of survivors completed the
      questionnaire. Median age of respondents was 41 years (range, 17-58). Respondents
      rated the website's usability with a mean SUS score of 72.5 (95 % CI, 69.2-74.9).
      The mean content rating was 3.7 (95 % CI, 3.5-3.8). No determinants were
      significantly related to the perceived usability or content satisfaction in
      multivariate analyses. Qualitative analysis revealed respondents' preference for
      more detailed and even scientific information on late effects. CONCLUSION:
      Respondents were satisfied with the usability and the contents of a website that
      targeted at their information needs. As knowledge about late effects is still
      limited among survivors, a website can be a valuable resource to improve their
      knowledge, promote healthy behavior, and in the end, improve their quality of
      life.

PMID- 23007885
TI  - High efficiency, site-specific transfection of adherent cells with siRNA using
      microelectrode arrays (MEA).
AB  - The discovery of RNAi pathway in eukaryotes and the subsequent development of
      RNAi agents, such as siRNA and shRNA, have achieved a potent method for silencing
      specific genes for functional genomics and therapeutics. A major challenge
      involved in RNAi based studies is the delivery of RNAi agents to targeted cells.
      Traditional non-viral delivery techniques, such as bulk electroporation and
      chemical transfection methods often lack the necessary spatial control over
      delivery and afford poor transfection efficiencies. Recent advances in chemical
      transfection methods such as cationic lipids, cationic polymers and nanoparticles
      have resulted in highly enhanced transfection efficiencies. However, these
      techniques still fail to offer precise spatial control over delivery that can
      immensely benefit miniaturized high-throughput technologies, single cell studies
      and investigation of cell-cell interactions. Recent technological advances in
      gene delivery have enabled high-throughput transfection of adherent cells, a
      majority of which use microscale electroporation. Microscale electroporation
      offers precise spatio-temporal control over delivery (up to single cells) and has
      been shown to achieve high efficiencies. Additionally, electroporation based
      approaches do not require a prolonged period of incubation (typically 4 hours)
      with siRNA and DNA complexes as necessary in chemical based transfection methods
      and lead to direct entry of naked siRNA and DNA molecules into the cell
      cytoplasm. As a consequence gene expression can be achieved as early as six hours
      after transfection. Our lab has previously demonstrated the use of microelectrode
      arrays (MEA) for site-specific transfection in adherent mammalian cell cultures.
      In the MEA based approach, delivery of genetic payload is achieved via localized
      micro-scale electroporation of cells. An application of electric pulse to
      selected electrodes generates local electric field that leads to electroporation
      of cells present in the region of the stimulated electrodes. The independent
      control of the micro-electrodes provides spatial and temporal control over
      transfection and also enables multiple transfection based experiments to be
      performed on the same culture increasing the experimental throughput and reducing
      culture-to-culture variability. Here we describe the experimental setup and the
      protocol for targeted transfection of adherent HeLa cells with a fluorescently
      tagged scrambled sequence siRNA using electroporation. The same protocol can also
      be used for transfection of plasmid vectors. Additionally, the protocol described
      here can be easily extended to a variety of mammalian cell lines with minor
      modifications. Commercial availability of MEAs with both pre-defined and custom
      electrode patterns make this technique accessible to most research labs with
      basic cell culture equipment.

PMID- 23007888
TI  - Lattice Microbes: high-performance stochastic simulation method for the reaction
      diffusion master equation.
AB  - Spatial stochastic simulation is a valuable technique for studying reactions in
      biological systems. With the availability of high-performance computing (HPC),
      the method is poised to allow integration of data from structural, single
      molecule and biochemical studies into coherent computational models of cells.
      Here, we introduce the Lattice Microbes software package for simulating such cell
      models on HPC systems. The software performs either well-stirred or spatially
      resolved stochastic simulations with approximated cytoplasmic crowding in a fast
      and efficient manner. Our new algorithm efficiently samples the reaction
      diffusion master equation using NVIDIA graphics processing units and is shown to
      be two orders of magnitude faster than exact sampling for large systems while
      maintaining an accuracy of !0.1%. Display of cell models and animation of
      reaction trajectories involving millions of molecules is facilitated using a plug
      in to the popular VMD visualization platform. The Lattice Microbes software is
      open source and available for download at http://www.scs.illinois.edu/schulten/lm

PMID- 23007889
TI  - Perinatal neuroblastoma of the pancreas.
AB  - Neuroblastoma is the most common solid tumor in infancy. Arising from the neural
      crest these tumors are usually located along the sympathetic chain from the neck
      to the pelvis and in the adrenal medulla. We report the case of a 3-week-old boy
      presenting with recurrent episodes of colicky pain. After ultrasound examination,
      magnetic resonance imaging and laboratory data a pancreatic neuroblastoma was
      suspected. Tumor resection via distal pancreatectomy and histologic investigation
      confirmed the diagnosis. Surgery is the treatment of choice in children with
      pancreatic masses, and is usually well tolerated even in the neonatal period.
      Conclusive diagnosis can be frequently established only by tumor resection or
      biopsy. Pancreatic neuroblastoma is an extremely rare tumor with only a few cases
      described in literature.

PMID- 23007891
TI  - Cognitive enhancements and the values of higher education.
AB  - Drugs developed to treat cognitive impairments are proving popular with healthy
      college students seeking to boost their focus and productivity. Concerned
      observers have called these practices a form of cheating akin to athletes' use of
      steroids, with some proposing testing students' urine to deter "academic doping."
      The ease with which critics analogize the academic enterprise to competitive
      sport, and the impulse to crack down on students using study drugs, reflect the
      same social influences and trends that spur demand for these interventions-our
      hyper-competitive culture, the commodification of education, and our attraction
      to technological quick-fixes. Rather than focusing on the technologies that are
      being put to troubling uses, we would be better served reforming the culture that
      makes these practices attractive.

PMID- 23007890
TI  - Molecular epidemiology of PRRSV from China's Guangxi Province between 2007 and
      2009.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is considered to be one of
      the most important infectious diseases affecting livestock. This study used gene
      sequence analysis of ORF5 and Nsp2 to determine the molecular epidemiology of
      PRRSV in different parts of the Guangxi province of China. These genes were
      selected due to their extensive variation within the genome. Out of 189 samples
      from animals suspected to have PRRS, 145 were PRRSV RNA positive. ORF5 and Nsp2
      gene sequence analysis of 31 of these samples showed that all of the Guangxi
      isolates were of type 2. A phylogenetic tree analysis based on ORF5 showed that
      the Guangxi isolates were divided into two groups. Most of these were closely
      related to highly pathogenic strains, showing a 30 amino acid deletion at
      positions 481 and 533-561 of Nsp2, but an additional unique isolate (GXNN06)
      possessed a further four amino acid deletion at positions 485-488 of Nsp2.

PMID- 23007892
TI  - Species differences in the antidiarrheal and antispasmodic activities of Lepidium
      sativum and insight into underlying mechanisms.
AB  - The aim of this study was to see if the crude extract of Lepidium sativum (Ls.Cr)
      exhibits species specificity in its antidiarrheal and antispasmodic activities
      along with insight into the underlying mechanisms using the in-vivo and in-vitro
      experiments. Ls.Cr inhibited castor oil-induced diarrhea in mice at doses (300
      and 1000 mg/kg) three times higher dose than for rats. In isolated rat ileum and
      jejunum, Ls.Cr completely inhibited carbachol (CCh), low K+ (25 mM) and high K+
      (80 mM)-induced contractions, while in guinea-pig tissues, Ls.Cr caused complete
      inhibition of only CCh-induced contraction. In rabbit tissues, Ls.Cr completely
      inhibited CCh and low K+-induced contractions sensitive to K+ channel
      antagonists. Pretreatment of guinea-pig and rat tissues with Ls.Cr caused a
      rightward shift in CCh-induced contractions in a pattern similar to dicyclomine,
      while in rabbit and rat tissues, Ls.Cr shifted isoprenaline curves to the left
      similar to papaverine. These data indicate that the antidiarrheal and
      antispasmodic activities of L. sativum are species dependent, mediating its
      antispasmodic effect through combinations of multiple pathways including
      activation of K+ channels, and inhibition of muscarinic receptors, Ca++ channels
      and PDE enzyme. Rat tissues showed the highest potency. Based on the results, we
      recommend using multiple species to know the real pharmacological profile of
      medicinal products.

PMID- 23007893
TI  - A wire-loop technique for implantation of an iliac branched device in a patient
      with previous surgery for a ruptured abdominal aortic aneurysm.
AB  - We described a modified technique for implanting a bridging stent-graft into an
      iliac branched device. A 79-year-old male who had received aortobiiliac synthetic
      graft surgery for a ruptured abdominal aortic aneurysm six months earlier was
      admitted to our unit for treatment of a left common iliac aneurysm involving the
      origin of the hypogastric artery. A standard technique was unsuccessful at
      implanting the bridging stent-graft, and therefore a wire-loop guidewire over the
      graft bifurcation was used to stabilize the contralateral sheaths and to complete
      the implantation.

PMID- 23007894
TI  - Special issue on mechanics of development.

PMID- 23007895
TI  - Prevalence of venous thromboembolism in patients with secondary polycythemia.
AB  - To investigate an association between secondary polycythemia and venous
      thromboembolism (VTE) risk, we performed a case-control study to compare the
      prevalence of VTE in participants with secondary polycythemia due to chronic
      obstructive pulmonary disease (COPD; N = 86) to that in age- and sex-matched
      controls with COPD without secondary polycythemia (N = 86). Although there was a
      significant difference in mean hematocrit between cases and controls (53.5% vs
      43.6%, respectively; P < .005), we identified no difference in the number of
      total or idiopathic VTE events in the 2 groups. Patients with VTE, however, had a
      significantly higher body mass index than patients without VTE. Our findings
      suggest that secondary polycythemia alone may not be a significant risk factor
      for VTE but that VTE risk in this population may be related to known risk factors
      such as obesity. The role of phlebotomy for VTE risk reduction secondary
      polycythemia is therefore questionable. 

PMID- 23007896
TI  - Artificial turf football fields: environmental and mutagenicity assessment.
AB  - The public has recently raised concerns regarding potential human health and
      environmental risks associated with tire crumb constituents in the artificial
      turf of football fields. The aim of the present study was to develop an
      environmental analysis drawing a comparison between artificial turf football
      fields and urban areas relative to concentrations of particles (PM10 and PM2.5)
      and related polycyclic aromatic hydrocarbons (PAHs), aromatic hydrocarbons
      (BTXs), and mutagenicity of organic extracts from PM10 and PM2.5. No significant
      differences were found between PM10 concentrations at an urban site and on a turf
      football field, both during warm and in cold seasons, either with or without on
      field activity. PM2.5 concentrations were significantly greater at the urban site
      in the cold season as was the ratio of PM2.5 to PM10. BTXs were significantly
      greater at urban sites than on turf football fields on both on warm and cold
      days. The ratio of toluene to benzene (T/B ratio) was always comparable with that
      of normal urban conditions. The concentration of PAHs on the monitored football
      fields was comparable with urban levels during the two different sampling
      periods, and the contribution of PAHs released from the granular material was
      negligible. PM10 organic extract mutagenicity for artificial turf football fields
      was greater, whereas PM2.5 organic extract mutagenicity was lower, compared with
      the urban site studied. However, both organic extract mutagenicity values were
      comparable with the organic extract mutagenicity reported in the literature for
      urban sites. On the basis of environmental monitoring, artificial turf football
      fields present no more exposure risks than the rest of the city.

PMID- 23007897
TI  - Contrasting patterns of urban expansion in Colombia, Ecuador, Peru, and Bolivia
      between 1992 and 2009.
AB  - The global urban population is increasing rapidly, but patterns of urban
      expansion differ greatly among countries. Urban transition theory predicts that
      the shift from low to high urbanization depends on a country's history and level
      of economic development. This study describes urban expansion in Colombia,
      Ecuador, Peru, and Bolivia between 1992 and 2009. Urban dynamics were analyzed by
      combining nighttime lights and census data from 4032 municipalities. High-lit
      areas (>52-63 pixel values) were correlated with urban populations across
      municipalities and years (R (2) > 0.90). Analyses showed that between 1992 and
      2009 Bolivia and Ecuador had rapid population growth and rapidly increasing high
      lit areas, while Peru and Colombia had lower rates of population growth and
      urbanization (i.e., expansion of high-lit areas). We demonstrate how nighttime
      lights can be a useful tool, providing a homogeneous platform for multi-scale
      analyses of urban growth.

PMID- 23007899
TI  - Molecules of ruthenium-based olefin metathesis catalysts as two- and three-photon
      absorbers.
AB  - Three ruthenium-based complexes exhibiting catalytic activity in olefin
      metathesis have been examined for the presence of interesting nonlinear optical
      (NLO) properties. Measurements were performed by the Z-scan technique using a
      tunable femtosecond laser system. This initial screening for potential new
      applications in photonics of complexes representative of a wide family of
      ruthenium-based olefin metathesis catalysts has found moderately strong two
      photon and three-photon absorption properties in relatively simple molecules that
      may lead to the development of a new class of strong nonlinear absorbers.

PMID- 23007898
TI  - [Supraglottic airway devices].
AB  - All guidelines and algorithms for the management of difficult airways include the
      use of supraglottic airway devices. This report provides information on the
      different types of these devices and gives selection criteria for different
      scenarios.

PMID- 23007900
TI  - Ion interactions with a new ditopic naphthalimide-based receptor: a
      photophysical, NMR and theoretical (DFT) study.
AB  - A new multi-component chemosensor system comprising a naphthalimide moiety as
      fluorophore is designed and developed to investigate receptor-analyte binding
      interactions in the presence of metal and non-metal ions. A dimethylamino moiety
      is utilized as receptor for metal ions and a thiourea receptor, having acidic
      protons, for binding anions. The system is characterized by conventional
      analytical methods. The absorption and fluorescence spectra of the system consist
      of a broad band typical for an intramolecular charge transfer (ICT). The effects
      of various metal-ion additives on the spectral behavior of the present sensor
      system are examined in acetonitrile. It is found that among the metal ions
      studied, alkali/alkaline earth-metal ions and transition-metal ions modulate the
      absorption and fluorescence spectra of the system. As an additional feature, the
      anion signaling behavior of the system in acetonitrile is studied. A decrease in
      fluorescence efficiency of the system is observed upon addition of fluoride and
      acetate anions. Fluorescence quenching is most effective in the case of fluoride
      ions. This is attributed to the enhancement of the photoinduced electron transfer
      from the anion receptor to the fluorophore moiety. Hydrogen-bond interactions
      between the acidic NH protons of the thiourea moiety and the F(-)  anions are
      primarily attributed to the fluoride-selective signaling behavior. Interestingly,
      a negative cooperativity for the binding event is observed when the interactions
      of the system are studied in the presence of both Zn(2+)  and F(-)  ions. NMR
      spectroscopy and theoretical calculations are also carried out to better
      understand the receptor-analyte binding.

PMID- 23007901
TI  - Risk predictors of underestimation and the need for sentinel node biopsy in
      patients diagnosed with ductal carcinoma in situ by preoperative needle biopsy.
AB  - BACKGROUND: Diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy
      showed a high rate of underestimation of invasiveness, and performing sentinel
      lymph node biopsy (SLNB) in DCIS patients was controversial. METHODS: We analyzed
      340 DCIS patients who were diagnosed by needle biopsies. Final pathology and
      clinicopathological features were reviewed. Predictors were accessed using the
      Chi-square test and a binary logistic regression model. RESULTS: The overall DCIS
      underestimation rate was 42.6%. The underestimation was significantly related to
      the palpability, mass or calcification by ultrasonography, grade, suspicious
      microinvasion, and biopsy method in univariate analysis. In multivariate
      analysis, palpability, ultrasonographic calcification or mass, suspicious
      microinvasion, and core needle biopsy were independent predictors of
      underestimation of invasive cancer. In cases with one or no risk predictors, the
      underestimation rate was 14.3%, whereas, in those with five predictors, it
      increased to 90.9%. Among 144 invasive cancer patients who underwent axillary
      staging, 15.4% had node metastasis. CONCLUSIONS: DCIS diagnosed by preoperative
      needle biopsy has a high probability of underestimation, and 15% of invasive
      cancer patients have node metastasis. SLNB may be justified in DCIS patients
      undergoing needle biopsies, and caution should be exercised in omitting SLNB in
      patients with one or no risk predictors.

PMID- 23007904
TI  - Combined use of fascia iliaca block, subarachnoid block and dexmedetomidine
      sedation for patients having fractured femur surgery.

PMID- 23007903
TI  - Ultrasound-guided trunk and core blocks in infants and children.
AB  - Regional anesthetic techniques for perioperative analgesia in children are being
      increasingly utilized with the reported advantages of providing superior
      analgesia, decreasing opioid consumption, and reducing opioid-related adverse
      effects. The following article reviews the available literature regarding core
      and trunk blocks in infants and children; specifically, transversus abdominis
      plane, ilioinguinal/iliohypogastric nerve, rectus sheath, lumbar plexus, and
      paravertebral and intercostal nerve blockade. The common indications and
      potential complications and adverse effects for each block are presented.
      Additionally, the anatomy and techniques needed for their performance are
      reviewed. Finally, a summary of the relevant literature in relation to each
      peripheral nerve block technique is included.

PMID- 23007905
TI  - Anesthesia for children with mitochondrial disorders: a national survey and
      review.
AB  - PURPOSE: Mitochondrial diseases are a heterogeneous group of disorders. Patients
      with such diseases often need general anesthesia for diagnostic procedures and
      surgery; guidelines are lacking for the anesthetic care of these patients.
      METHODS: We conducted a survey to investigate the current practices of pediatric
      anesthesiologists in the US in order to determine and document current practice.
      The survey consisted of twenty questions, including two demographic questions. A
      link to the survey was sent via email to members of the Society for Pediatric
      Anesthesia (2440), and was available online for 14 weeks. RESULTS: Only 503
      completed the survey: a response rate of 20.61 %. Among the responders, 93.2 %
      had children with mitochondrial disorders among their patients, but only 11 % had
      institutional guidelines for such cases in place. Among the responders, 80.3 %
      used the standard nil per os (NPO) status guidelines, while the rest give
      intravenous dextrose solution once NPO was in effect. Only 18.3 % took
      precautions for malignant hyperthermia during treatment. The majority of the
      practitioners chose sevoflurane as the safest inhaled agent for induction and
      maintenance (89.7 and 78.5 %, respectively). Regional anesthesia was deemed safe
      by 97.3 % of the responders. Lactated Ringer's solution was considered safe for
      these children by 49 %; only 47.8 % used dextrose-containing fluids for fluid
      replacement. The blood glucose was monitored by 72.7 %, and the majority (85 %)
      of this monitoring was done in a postanesthesia care unit. CONCLUSION: Although
      the response rate was low, the majority of the responders provide care to these
      children routinely, so it can be inferred that the results of this survey are the
      closest published results to the true trend.

PMID- 23007906
TI  - Management of peripartum cardiomyopathy.
AB  - OPINION STATEMENT: Peripartum cardiomyopathy is diagnosed in women who develop
      systolic heart failure in the last month of pregnancy or within 5 months of
      delivery. This diagnosis should not be made in women with pre-existing cardiac
      disease or another cause of cardiac dysfunction. To prevent delay in diagnosis
      and treatment, a high index of suspicion is required given the overlapping
      symptoms of late pregnancy and heart failure. Traditional heart failure medical
      therapies are indicated, although drugs must be carefully reviewed for safety
      during pregnancy and lactation. Long-term prognosis is largely determined by the
      degree of ventricular recovery. Patients with acute or persistent hemodynamic
      compromise despite medical therapy should be considered for mechanical
      circulatory support and evaluated promptly for cardiac transplantation. A
      multidisciplinary team is required to care for patients with peripartum
      cardiomyopathy through parturition and beyond. All peripartum cardiomyopathy
      patients should be counseled that repeat pregnancy can negatively impact cardiac
      function and lead to recurrent heart failure or even death. Patients with
      persistent ventricular dysfunction should be strongly advised against another
      pregnancy.

PMID- 23007907
TI  - Gene-expression analysis reveals that embryonic stem cells cultured under
      osteogenic conditions produce mineral non-specifically compared to marrow stromal
      cells or osteoblasts.
AB  - Pluripotent cells, such as embryonic stem cells (ESCs), divide indefinitely and
      can differentiate to form mineralised nodules in response to osteogenic
      supplements. This suggests that they may be used as a cell source for bone
      replacement strategies. Here, we related the expression of osteogenic and
      chondrogenic genes in cultures of murine ESCs, marrow stromal cells (MSCs) and
      calvarial osteoblasts (OBs) cultured under osteogenic conditions to the
      biochemical composition and quantity of mineral formed. Mineralisation, measured
      by calcium sequestration, was >2-fold greater in ESC cultures than in either MSCs
      or OBs. Micro-Raman spectroscopy and spectral mapping revealed a lower mineral-to
      matrix ratio and confirmed a more diffuse pattern of mineralisation in ESCs
      compared to MSCs and OBs. Baseline expression of chondrogenic and osteogenic
      genes was between 1 and 4 orders of magnitude greater in MSCs and OBs than in
      ESCs. Osteogenic culture of MSCs and OBs was accompanied by increases in
      osteogenic gene expression by factors of ~100 compared to only ~10 in ESCs.
      Consequentially, peak expression of osteogenic and chondrogenic genes was greater
      in MSCs and OBs than ESCs by factors of 100-1000, despite the fact that
      mineralisation was more extensive in ESCs than either MSCs or OBs. We also
      observed significant cell death in ESC nodules. We conclude that the mineralised
      material observed in cultures of murine ESCs during osteogenic differentiation
      may accumulate non-specifically, perhaps in necrotic cell layers, and that
      thorough characterisation of the tissue formed by ESCs must be achieved before
      these cells can be considered as a cell source for clinical applications.

PMID- 23007908
TI  - Interleukin-1beta modulates endochondral ossification by human adult bone marrow
      stromal cells.
AB  - Inflammatory cytokines present in the milieu of the fracture site are important
      modulators of bone healing. Here we investigated the effects of interleukin-1beta
      (IL-1beta) on the main events of endochondral bone formation by human bone marrow
      mesenchymal stromal cells (BM-MSC), namely cell proliferation, differentiation
      and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of
      IL-1beta (50 pg/mL) enhanced colony-forming units-fibroblastic (CFU-f) and 
      osteoblastic (CFU-o) number (up to 1.5-fold) and size (1.2-fold) in the absence
      of further supplements and glycosaminoglycan accumulation (1.4-fold) upon BM-MSC
      chondrogenic induction. In osteogenically cultured BM-MSC, IL-1beta enhanced
      calcium deposition (62.2-fold) and BMP-2 mRNA expression by differential
      activation of NF-kappaB and ERK signalling. IL-1beta-treatment of BM-MSC
      generated cartilage resulted in higher production of MMP-13 (14.0-fold) in vitro,
      mirrored by an increased accumulation of the cryptic cleaved fragment of
      aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in
      vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas),
      resulting in the formation of mature bone and bone marrow after 12 weeks. In
      conclusion, IL-1beta finely modulates early and late events of the endochondral
      bone formation by BM-MSC. Controlling the inflammatory environment could enhance
      the success of therapeutic approaches for the treatment of fractures by resident
      MSC and as well as improve the engineering of implantable tissues.

PMID- 23007909
TI  - Multifunctional surfaces with biomimetic nanofibres and drug-eluting micro
      patterns for infection control and bone tissue formation.
AB  - For long-term orthopaedic implants, the creation of a surface that is repulsive
      to bacteria while adhesive to tissue cells represents a promising strategy to
      control infection. To obtain such multifunctional surfaces, two possible
      approaches were explored to incorporate a model antibiotic, rifampicin (Rf), into
      the osteogenic polycaprolactone (PCL)/chitosan (CHS) biomimetic nanofibre meshes
      by (1) blending Rf into the electrospinning solutions and then electrospinning
      into nanofibres (i.e., Rf-incorporating fibres), or (2) depositing Rf-containing
      poly(D,L-lactic-co-glycolic) acid (PLGA) micro-patterns onto the PCL/chitosan
      nanofibre meshes via ink-jet printing (i.e., Rf-eluting micro-pattern/fibre).
      Rapid release of Rf from both meshes was measured even though a relatively slower
      release rate was obtained from the Rf-eluting micro-pattern ones. Antibacterial
      assay with Staphylococcus epidermidis showed that both mesh surfaces could
      effectively kill bacteria and prevent biofilm formation. However, only Rf-eluting
      micro-pattern meshes favoured the attachment, spreading and metabolic activity of
      preosteoblasts in the cell culture study. Furthermore, the Rf-eluting micro
      pattern meshes could better support the osteogenic differentiation of
      preosteoblasts by up-regulating the gene expression of bone markers (type I
      collagen and alkaline phosphatase). Clearly, compared to Rf-incorporating
      nanofibre meshes, Rf-eluting micro-patterns could effectively prevent biofilm
      formation without sacrificing the osteogenic properties of PCL/chitosan nanofibre
      surfaces. This finding provides an innovative avenue to design multifunctional
      surfaces for enhancing bone tissue formation while controlling infection.

PMID- 23007910
TI  - Reactive oxygen species (ROS)--a family of fate deciding molecules pivotal in
      constructive inflammation and wound healing.
AB  - Wound healing requires a fine balance between the positive and deleterious
      effects of reactive oxygen species (ROS); a group of extremely potent molecules,
      rate limiting in successful tissue regeneration. A balanced ROS response will
      debride and disinfect a tissue and stimulate healthy tissue turnover; suppressed
      ROS will result in infection and an elevation in ROS will destroy otherwise
      healthy stromal tissue. Understanding and anticipating the ROS niche within a
      tissue will greatly enhance the potential to exogenously augment and manipulate
      healing. Tissue engineering solutions to augment successful healing and
      remodelling of wounded or diseased tissue rely on a controlled balance between
      the constructive and destructive capacity of the leukocyte secretome, including
      ROS. This review comprehensively considers leukocyte derived ROS in tissue repair
      with particular interest in surgical intervention with inclusion of a
      biomaterial. The article considers ROS fundamental chemistry, formation,
      stimulation and clearance before applying this to discuss the implications of ROS
      in healing tissue with and without a biomaterial. We also systematically discuss
      ROS in leukocyte signalling and compare and contrast experimental means of
      measuring ROS.

PMID- 23007911
TI  - Vascularisation of porous scaffolds is improved by incorporation of adipose
      tissue-derived microvascular fragments.
AB  - In tissue engineering, the generation of tissue constructs comprising preformed
      microvessels is a promising strategy to guarantee their adequate vascularisation
      after implantation. Herein, we analysed whether this may be achieved by seeding
      porous scaffolds with adipose tissue-derived microvascular fragments. Green
      fluorescent protein (GFP)-positive microvascular fragments were isolated by
      enzymatic digestion from epididymal fat pads of male C57BL/6-TgN(ACTB-EGFP)1Osb/J
      mice. Nano-size hydroxyapatite particles/poly(ester-urethane) scaffolds were
      seeded with these fragments and implanted into the dorsal skinfold chamber of
      C57BL/6 wild-type mice to study inosculation and vascularisation of the implants
      by means of intravital fluorescence microscopy, histology and
      immunohistochemistry over 2 weeks. Empty scaffolds served as controls. Vital
      microvascular fragments could be isolated from adipose tissue and seeded onto the
      scaffolds under dynamic pressure conditions. In the dorsal skinfold chamber, the
      fragments survived and exhibited a high angiogenic activity, resulting in the
      formation of GFP-positive microvascular networks within the implants. These
      networks developed interconnections to the host microvasculature, resulting in a
      significantly increased functional microvessel density at day 10 and 14 after
      implantation when compared to controls. Immunohistochemical analyses of vessel
      seeded scaffolds revealed that >90 % of the microvessels in the implants' centre
      and ~60 % of microvessels in the surrounding host tissue were GFP-positive. This
      indicates that the scaffolds primarily vascularised by external inosculation.
      These novel findings demonstrate that the vascularisation of implanted porous
      scaffolds can be improved by incorporation of microvascular fragments.
      Accordingly, this approach may markedly contribute to the success of future
      tissue engineering applications in clinical practice.

PMID- 23007912
TI  - Mechanical loading and how it affects bone cells: the role of the osteocyte
      cytoskeleton in maintaining our skeleton.
AB  - Lack of physical activity causes bone loss and fractures not only in elderly
      people, but also in bedridden patients or otherwise inactive youth. This is fast
      becoming one of the most serious healthcare problems in the world. Osteocytes,
      cells buried within our bones, stimulate bone formation in the presence of
      mechanical stimuli, as well as bone degradation in the absence of such stimuli.
      As yet, we do not fully comprehend how osteocytes sense mechanical stimuli, and
      only know a fraction of the whole range of molecules that osteocytes subsequently
      produce to regulate bone formation and degradation in response to mechanical
      stimuli. This dramatically hampers the design of bone loss prevention strategies.
      In this review we will focus on the first step in the cascade of events leading
      to adaptation of bone mass to mechanical loading, i.e., on how osteocytes are
      able to perceive mechanical stimuli placed on whole bones. We will place
      particular emphasis on the role of the osteocyte cytoskeleton in mechanosensing.
      Given the crucial importance of osteocytes in maintaining a proper resistance
      against bone fracture, greater knowledge of the molecular mechanisms that govern
      the adaptive response of osteocytes to mechanical stimuli may lead to the
      development of new strategies towards fracture prevention and enhanced bone
      healing.

PMID- 23007913
TI  - Biochemical and molecular characterisation of acetylcholinesterase in four field
      populations of Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).
AB  - BACKGROUND: The oriental fruit fly, Bactrocera dorsalis, is a major pest that
      infects fruits and agricultural products worldwide. The latest resistance
      monitoring of B. dorsalis from mainland China has identified high levels of
      resistance to insecticides. In this study, the biochemical and molecular
      characteristics of acetylcholinesterase (AChE) in four field populations of B.
      dorsalis are investigated. RESULTS: Among the four populations, the DG population
      and its purified AChE were found to be the least susceptible to malathion and
      five inhibitors, whereas the KM population and its purified AChE were the most
      susceptible. The highest catalytic activity of purified AChE was found for the KM
      population, and the catalytic activity of the DG population was the lowest. Among
      developmental stages, the AChE purified from larvae was found to be the most
      insusceptible to inhibitors, but its catalytic activity was the highest. Sequence
      analysis of the cDNA encoding AChE showed that some residue differences existed.
      However, no significant differences in expression levels of the AChE gene among
      populations and developmental stages were detected. CONCLUSION: The results
      suggest that the decrease in susceptibility of B. dorsalis was mainly caused by
      decrease in AChE activity, and they provide a broad view on the relation between
      AChE and resistance.

PMID- 23007914
TI  - Ginsenosides Rb1 and Rd regulate proliferation of mature keratinocytes through
      induction of p63 expression in hair follicles.
AB  - Ginsenosides Rb1 and Rd are the two main types of ginsenosides in Panax ginseng
      and have been used as an additive to against alopecia. However, the mechanisms
      involved are largely unknown. To determine how ginsenosides prevent hair loss, we
      topically applied protopanaxadiol-type ginsenosides Rb1 and Rd over the shaved
      skin of B57CL/6 mice, and monitored and assessed them for 35 days. We then
      investigated the effects of ginsenosides on cell genesis in different phases of
      adult hair follicles (HFs), using 5-bromo-2'-deoxyuridine as a marker for
      dividing cells. Moreover, p63, a specific marker and a major regulator of
      keratinocyte progenitor cells of the multi-layered epithelia, was detected in
      epidermis. Results indicated that treatment with ginsenosides Rb1 and Rd
      increased cell proliferation in both anagen and telogen of HFs. However, it had
      no significant effect on the survival of cells in the bulge and upper follicle
      region. Investigation of p63 demonstrated that up-regulation of p63 expression in
      the matrix and outer root sheath might be one of the mechanisms by which
      ginsenosides Rb1 and Rd promote cell proliferation in HFs. Our study reveals a
      novel mechanism by which ginsenoside promotes hair growth through p63 induction
      in follicular keratinocytes and indicates that ginsenosides Rb1 and Rd might be
      developed as a therapeutic agent for the prevention of hair loss.

PMID- 23007916
TI  - Low-level-laser irradiation induces photorelaxation in coronary arteries and
      overcomes vasospasm of internal thoracic arteries.
AB  - BACKGROUND AND OBJECTIVE: As low-level laser irradiation (LLLI) seems to induce
      vasodilation besides many other known biological effects, LLLI has been
      increasingly used in therapy of medical conditions with various irradiation
      parameters. The aim of this study was to investigate the effect of LLLI on
      photorelaxation of human coronary and internal thoracic arteries (ITA). MATERIALS
      AND METHODS: Thirty vessel segments of ITA used for routine coronary artery
      bypass grafting as well as left anterior descending coronary arteries (LAD) of
      patients undergoing cardiac transplantation were cut into 4-mm rings stored in a
      modified Krebs-Henseleit solution and evaluated in a myograph. Both types of
      vessel segments were irradiated by a semiconductor non-thermal GaAs diode laser
      operating at a wavelength of 680 nm. After precontraction with thromboxane
      agonist U44619, respective relaxation responses were evaluated and compared to
      pharmacological dilatation induced by substance P. RESULTS: Mean pharmacological
      vasodilation by substance P was 22.6 +/- 3.3%, 12.8 +/- 1.4%, and 20.4 +/- 3.2%
      in macroscopic healthy LAD, LAD with atheromatous plaque, and ITA, respectively.
      Average photorelaxation induced by LLLI was 16.5 +/- 2.0%, 1.9 +/- 1.7%, and 6.8
      +/- 4.7%, accordingly. Vasodilatatory responses induced either by substance P or
      administration of LLLI were significantly decreased in LAD with atheromatous
      plaque (P < 0.0001). Vasospasms of ITA segments occurring during experiments
      could be abandoned when LLLI was administered. CONCLUSION: Macroscopic healthy
      LAD exposed to LLLI revealed significant photorelaxation. With the administration
      of LLLI, 73% of the maximal obtainable effect by an endothelium-dependent
      vasodilator could be reached. Furthermore, LLLI has the potential to overcome
      vasospasms of ITA.

PMID- 23007917
TI  - [Split thickness skin graft for coverage of soft tissue defects].
AB  - OBJECTIVE: Coverage of skin or soft tissue defects of various sizes by
      transplantation of spit thickness skin grafts. INDICATIONS: Skin or soft tissue
      defects of any size or location as long as there is a good blood supply to the
      wound bed. CONTRAINDICATIONS: Wound bed providing poor blood supply (e.g., tendon
      or bone), vessels or nerve without soft tissue coverage, any kind of implant
      material which is not covered by vital soft tissue. Relative contraindications
      include defect position at the flexion side of joints or other mechanically
      stressed locations (e.g., heel, neck) and local infection. SURGICAL TECHNIQUE: By
      meticulous debridement of the recipient site and coagulation of venous bleedings,
      the recipient site is prepared for skin grafting. Thereafter, the split thickness
      skin graft is harvested and, if necessary, modified by the meshing procedure.
      Then, the skin graft is placed in the defect and fixated at the wound margins. To
      promote healing, a special compression dressing is used to cover the split
      thickness skin graft. In case of uneventful wound healing, this dressing should
      be left in place for 5 days. POSTOPERATIVE MANAGEMENT: After removal of the
      compression dressing, daily changes are done using double layers of fatty gauze,
      alternated with periods without dressing. In the case of uneventful healing, the
      skin transplant can be covered starting in week 2 with a thin film of cream
      ointment. RESULTS: Split thickness skin grafting is a routine maneuver in
      reconstructive surgery and allows predictable, good results. Partial skin graft
      losses are mostly due to a combination of inadequate debridement and local
      infection. If the operation in done technically correct, total graft losses are
      rare.

PMID- 23007918
TI  - [Minimally invasive plate osteosynthesis of the distal tibia].
AB  - OBJECTIVE: Minimally invasive plate osteosynthesis of distal metaphyseal and/or
      diaphyseal tibial fractures. INDICATIONS: Extraarticular tibial fractures or
      distal tibial fractures with simple intraarticular components (AO 42 A-C + AO 43
      A, C1, C2) of the distal tibia shaft. Closed or open soft tissue conditions, most
      suitable for closed soft tissue damage Oestern-Tscherne grade I-II.
      CONTRAINDICATIONS: High degree open fractures, where the plate would not be
      covered by soft tissue. Comminuted Pilon fractures. SURGICAL TECHNIQUE: Closed
      reduction manually, over the plate or the external fixator/large distractor.
      Short incision on the medial malleolus. Epiperosteal insertion of the plate
      anteromedial. Improve reduction stepwise and insertion of screws on each main
      fragment. Relative stability is achieved by using bridging techniques. Fibula
      fixation in special cases. POSTOPERATIVE MANAGEMENT: Mobilization after 1-3 days
      with toe-touch weight bearing. Full weight bearing after 8-10 weeks. Implant
      removal optional after 1-2 years in cases of soft tissue irritation. RESULTS:
      Uneventful healing with good function was observed in 85% of patients within 4
      months. Delayed unions were observed in 5-10% of cases and nonunions or
      malalignment were observed in 5% of patients. All patients were satisfied with
      function at the 2-year follow-up.

PMID- 23007920
TI  - Peroxynitrous acid: controversy and consensus surrounding an enigmatic oxidant.
AB  - The isomerisation of ONOOH to NO(3)(-) and H(+), some oxidations and all
      hydroxylations and nitrations of aromatic compounds are first-order in ONOOH and
      zero-order in the compounds that are modified. These reactions are widely
      believed to proceed via homolysis of ONOOH into HO and NO(2) to an extent of ca.
      30%. We review the evidence pro and contra homolysis in studies that involve (1)
      thermochemical considerations, (2) isomerisation to NO(3)(-) and H(+), (3)
      decomposition to NO(2)(-) and O(2), (4) HO scavenger studies, (5) deuterium
      isotope effects, (6) (18)O-scrambling studies, (7) electrochemistry, (8) CIDNP
      NMR, and (9) photolysis. Our conclusion is that homolysis may be involved to a
      minor extent of ca. 5%. The initiation of ONOOH isomerisation may be visualised
      as an out-of-plane vibration of the terminal HO-group relative to the nitrogen.
      At ONOO(-) concentrations exceeding 0.1 mM and near neutral pH,
      disproportionation to NO(2)(-) and O(2) occurs; such disproportionations are
      typical for peroxy acids. For oxidation and nitration of organic substrates, we
      favour a mechanism involving initial formation of an adduct between the compound
      to be oxidised or nitrated and ONOOH.

PMID- 23007919
TI  - [Minimally invasive plating osteosynthesis of proximal humeral shaft fractures
      with long PHILOS plates].
AB  - OBJECTIVE: Closed reduction and minimally invasive stabilization of proximal
      humeral shaft fractures with long PHILOS plates. The presented technique enables
      stable extramedullary fixation of the fractures without affecting surrounding
      nerves. INDICATIONS: Proximal humeral shaft fractures that may not be fixed by
      intramedullary nailing because of a narrow, deformed or occupied intramedullary
      canal or because of open growth plates. CONTRAINDICATIONS: Fractures that may not
      be reduced adequately by traction or with percutaneous techniques. Furthermore,
      fractures with delayed or nonunion and pseudarthrosis should not be treated with
      this technique. SURGICAL TECHNIQUE: An anterolateral delta split approach is used
      to create an epiperiosteal tunnel along the humeral shaft from proximally to
      distally. A second incision is made distally at the lateral border of the biceps
      muscle. The brachialis muscle is dissected longitudinally. The PHILOS plate is
      twisted so that the proximal part of the plate can be placed laterally and the
      distal part anterolaterally at the humeral shaft. The plate is inserted into the
      epiperiostal tunnel and fixed with percutaneous screws. POSTOPERATIVE MANAGEMENT:
      The arm is immobilized in a Gilchrest bandage until wounds are healed. Active
      assisted physiotherapeutic mobilization without loading starts on the first
      postoperative day. Active mobilization starts 8-12 weeks postoperatively. In
      cases of soft tissue irritation the PHILOS plate may be removed after 1 year.
      RESULTS: Between 2005 and 2011 a total of 16 patients (8 women and 8 men) were
      treated with the presented technique. The patients mean age was 61 years.
      According to the AO classification, five fractures were classified as type A,
      eight as type B and three fractures as type C. All patients had clinical and
      radiological follow-up examinations after a mean of 24 months (12-38 months). All
      fractures showed complete bony consolidation at the final follow-up. The mean
      Constant-Murley score was 81 points representing 84% of the Constant-Murley score
      of the healthy contralateral shoulder. The average DASH score was 33 points and
      the mean SF36 was 85 points.

PMID- 23007921
TI  - Metastatic papillary thyroid carcinoma in the thigh with unusual cytologic
      features.

PMID- 23007922
TI  - Analysis of global components in Ganoderma using liquid chromatography system
      with multiple columns and detectors.
AB  - In present study, a multiple columns and detectors liquid chromatography system
      for analysis of global components in traditional Chinese medicines was developed.
      The liquid chromatography system was consist of three columns, including size
      exclusion chromatography column, hydrophilic interaction chromatography column,
      and reversed phase chromatography column, and three detectors, such as diode
      array detector, evaporative light scattering detector, and mass spectrometry
      detector, based on column switching technique. The developed multiple columns and
      detectors liquid chromatography system was successfully applied to the analysis
      of global components, including macromolecular (polysaccharides), high
      (nucleosides and sugars)-, and low (triterpenes)-polarity small molecular
      compounds in Ganoderma, a well-known Chinese medicinal mushroom. As a result, one
      macromolecular chromatographic peak was found in two Ganoderma species, 19
      components were identified in Ganoderma lucidum (two sugars, three nucleosides,
      and 14 triterpenes), and four components (two sugars and two nucleosides) were
      identified in Ganoderma sinense. The developed multiple columns and detectors
      liquid chromatography system was helpful to understand comprehensive chemical
      characters in TCMs.

PMID- 23007923
TI  - Midterm survival of infants requiring postoperative extracorporeal membrane
      oxygenation after Norwood palliation.
AB  - This study reports the mid-term survival for neonates undergoing extracorporeal
      membrane oxygenation (ECMO) after Norwood palliation at a single center. Limited
      data exist on the mid-term survival of patients undergoing ECMO after Norwood
      palliation. We reviewed our ECMO experience from July 1994 to October 2008 and
      compared two groups: patients who required ECMO after Norwood palliation and
      patients who underwent Norwood palliation without ECMO. We analyzed 30-day
      survival, survival to hospital discharge, and survival to most recent follow-up.
      One hundred sixty patients underwent Norwood palliation for hypoplastic left
      heart syndrome (HLHS) and its variants. A total of 32 patients (20%) required
      postoperative ECMO. Using Kaplan-Meier analysis, the predicted survival rates for
      Norwood/non-ECMO patients to 30 days, 1 year, and 3 years after the procedure are
      87.6% (CI 79.5-91.5%), 62.5% (CI 54.3-71.0%), and 59.9% (CI 50.8-67.8%),
      respectively. Survival to 30 days, 1 year, and 3 years after Norwood was
      significantly decreased in Norwood/ ECMO patients, with predicted survival rates
      of 50.0% (CI 31.9-65.7%), 24.6% (CI 11.4-40.4), and 13.2% (CI 3.9-28.3%),
      respectively (p < 0.0001). Risk factors for hospital mortality included
      nonelective or emergency placement onto ECMO, longer duration of ECMO support,
      and the development of acute renal failure while on ECMO. Of the original
      Norwood/ECMO hospital survivors, only half of these patients survived a mean of
      nearly 4 years. ECMO after Norwood palliation is associated with significant
      mortality. Our data suggest that neonates who require ECMO after Norwood
      palliation are prone to continued attrition once discharged from the hospital.

PMID- 23007924
TI  - Association of rheumatoid arthritis risk alleles with response to anti-TNF
      biologics: results from the CORRONA registry and meta-analysis.
AB  - In this study, we investigated whether genetic variants known to be related with
      susceptibility to rheumatoid arthritis (RA) are also associated with response to
      therapy with anti-tumor necrosis factor (anti-TNF) biologics; 233 patients
      enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA)
      RA registry were studied. Findings were combined with results from an
      international collaborative study (N = 1,283) in a meta-analysis (N = 1,516).
      Multivariate models investigating the association between single nucleotide
      polymorphisms (SNPs) and change in RA disease activity were adjusted for age,
      gender, concomitant methotrexate, and baseline disease activity. In the CORRONA
      cohort, nominal associations with disease activity improvement were observed for
      the rs1980422 SNP of the CD28 gene in multivariate models (coefficient -0.377, p
      = 0.005) but were not significant after adjustment for multiple comparisons (q =
      0.10). In the meta-analysis, the only SNP with nominal associations with change
      in DAS28 was the rs2812378 SNP of the CCL21 gene (coefficient 1.9195, p =
      0.0068). This association was not significant after adjustment for multiple
      comparisons (q = 0.143). We conclude that the established RA risk alleles studied
      were not significantly associated with response to anti-TNF biologics in the
      CORRONA cohort or the meta-analysis.

PMID- 23007925
TI  - Anti-inflammatory effects of Z-ligustilide nanoemulsion.
AB  - The Z-ligustilide (LIG) was studied for its anti-inflammatory activities with
      prepared LIG nanoemulsions (LIGNE). Healthy male adult Wistar rats were used in
      the study. Endotoxin-induced uveitis (EIU) was induced by a footpad injection of
      200 MUg lipopolysaccharide. EIU rats were administered orally with saline, LIG
      (20 mg/kg/day), and LIGNE (20 mg LIG /kg/day), respectively. Twenty-four hours
      later, rats were euthanized, and blood was collected from either right marginal
      ear vein to estimate inflammatory cells and inflammatory mediators. The drug
      dissolution profiles of LIGNE in both phosphate buffer pH 6.8 and 0.1 N HCl
      showed complete dissolution within 20 min. Pharmacokinetic studies suggested a
      significant increase (P < 0.0001) in the C pmax and AUC0->24 h were observed in
      the LIGNE group when compared with the LIG group. LIGNE significantly reduced the
      levels of tumor necrosis factor alpha, interleukin 1 beta, vascular endothelial
      growth factor alpha, and interleukin-17. The anti-inflammatory animal testing
      revealed that LIGNE led to an improvement in oral bioavailability.

PMID- 23007926
TI  - Association of serum soluble human leukocyte antigen-G levels with chronic
      hepatitis B virus infection.
AB  - Human leukocyte antigen-G is involved in immunotolerogenic, inflammatory and
      carcinogenic process. This study investigated serum soluble HLA-G (sHLA-G) levels
      in patients with chronic hepatitis B virus (HBV) infection according to the
      infection phases and clinical diagnoses. The study included 223 patients with
      chronic HBV infection [phases: 38 immune-tolerant (IT), 83 immune clearance (IC),
      30 non/low-replicative (LR) and 72 HBeAg negative hepatitis (ENH); diagnoses: 38
      asymptomatic HBV carriers (ASC), 98 chronic hepatitis (CH), 46 cirrhosis (LC) and
      41 hepatocellular carcinoma (HCC)], 62 HBV infection resolvers and 66 healthy
      controls. The sHLA-G levels in patients were elevated compared with resolvers and
      healthy controls (P < 0.001). According to phases, sHLA-G levels were higher in
      IC and ENH than in IT (P = 0.017 and P = 0.001, respectively). Serum sHLA-G
      levels were also higher in ENH than in LR (P = 0.008). According to diagnoses,
      sHLA-G levels in HCC were significantly increased compared with LC, CH and ASC (P
      = 0.010, P < 0.001 and P < 0.001, respectively). Serum sHLA-G levels were higher
      in CH than in ASC (P = 0.039). The sHLA-G levels in IC, ENH and CH were
      correlated with alanine aminotransferase levels (P = 0.011, P = 0.010 and P <
      0.001, respectively). It is concluded that sHLA-G is involved in the pathogenesis
      of chronic HBV infection and correlates with infection phases and clinical
      diseases, suggesting the value in evaluating disease activity and defining
      clinical diagnosis.

PMID- 23007927
TI  - Parotidectomy and neck dissection in the management of conjunctival melanoma: are
      they necessary?
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this study were to review traditional
      techniques for the management of conjunctival melanoma and assess the need for
      parotidectomy and neck dissection in the management of conjunctival melanoma.
      STUDY DESIGN: Retrospective review. METHODS: This study was a retrospective
      review conducted in a tertiary academic medical center of patients diagnosed with
      conjunctival melanoma over a 20-year period RESULTS: There were 39 patients
      diagnosed with conjunctival melanoma identified from January 1990 to December
      2010. Follow-up varied from 2 to 201 months (median, 25 months). Of the patients,
      16 (41%) had local recurrences at the primary site, two (13%) of whom later
      presented with parotid disease. One patient with parotid recurrence had a
      subsequent neck dissection for confirmed metastatic spread. No patient in this
      series had metastatic cervical disease without initial spread to the parotid. The
      probability of disease-free survival at 1, 2, and 5 years was 77%, 68%, and 50%,
      respectively. The probability of parotid free progression at 1, 2, and 5 years
      was 100%, 96%, and 90%, respectively. CONCLUSIONS: Conjunctival melanoma is a
      rare malignancy traditionally managed with aggressive treatment to optimize local
      control. The role for staging parotidectomy with or without neck dissection has
      been heavily debated. Based on our review, parotidectomy only needs to be
      undertaken when high suspicion for metastatic spread is present, such as a
      palpable or radiographically evident mass. In addition, without documented
      parotid disease, neck dissection is not required.

PMID- 23007928
TI  - C-peptide-stimulated nitric oxide production in a cultured pulmonary artery
      endothelium is erythrocyte mediated and requires Zn(2+).
AB  - BACKGROUND: C-peptide has been shown to stimulate the production of nitric oxide
      (NO) in aortic endothelial cells via activation of endothelial nitric oxide
      synthase (eNOS) through an increased calcium influx. Here, results obtained using
      cultured bovine pulmonary artery endothelial cells (bPAECs) suggest that C
      peptide does not induce eNOS activation directly in cultured pulmonary artery
      endothelium. However, C-peptide has been shown to stimulate the release of ATP
      from erythrocytes, a well-documented stimulus of eNOS activity in the pulmonary
      endothelium. Therefore, studies were performed to examine if C-peptide can
      indirectly stimulate NO production in a cultured pulmonary endothelium that is
      erythrocyte mediated. METHODS: NO production and free intracellular calcium
      changes were monitored in immobilized bPAECs using specific intracellular
      fluorescent probes after stimulation with adenosine triphosphate (ATP), calcium
      ionophore A23187, or C-peptide. A microfluidic device enabled immobilized bPAECs
      to interact with flowing erythrocytes in the presence and absence of C-peptide to
      determine the role of the erythrocyte in C-peptide-stimulated NO production in
      cultured bPAECs. RESULTS: ATP and the calcium ionophore stimulate significant
      increases in both intracellular NO production and influx of free calcium in
      cultured bPAECs. In contrast, C-peptide, ranging from physiological to above
      physiological concentrations, was unable to stimulate NO production or calcium
      influx in the bPAECs. However, when erythrocytes were pre-incubated with a
      mixture containing physiological concentrations of C-peptide with Zn(2+) and
      haemodynamically pumped beneath bPAECs cultured on a microfluidic device, an 88.6
      +/- 7.5% increase in endothelial NO production was observed. CONCLUSIONS: C
      peptide does not affect NO production in bPAECs directly but can impact NO
      production through an erythrocyte-mediated mechanism. Furthermore, in the absence
      of Zn(2+), C-peptide does not stimulate this NO production directly or
      indirectly. These results suggest that C-peptide, in the presence of Zn(2+), may
      be a determinant in purinergic receptor signalling via its ability to stimulate
      the release of ATP from erythrocytes.

PMID- 23007929
TI  - Computer tomography assessment of pedicle screw placement in thoracic spine:
      comparison between free hand and a generic 3D-based navigation techniques.
AB  - INTRODUCTION: Although pedicle screw fixation is a well-established technique for
      the lumbar spine, screw placement in the thoracic spine is more challenging
      because of the smaller pedicle size and more complex 3D anatomy. The
      intraoperative use of image guidance devices may allow surgeons a safer, more
      accurate method for placing thoracic pedicle screws while limiting radiation
      exposure. This generic 3D imaging technique is a new generation intraoperative CT
      imaging system designed without compromise to address the needs of a modern OR.
      AIM: The aim of our study was to check the accuracy of this generic 3D navigated
      pedicle screw implants in comparison to free hand technique described by Roy
      Camille at the thoracic spine using CT scans. MATERIAL AND METHODS: The material
      of this study was divided into two groups: free hand group (group I) (18
      patients; 108 screws) and 3D group (27 patients; 100 screws). The patients were
      operated upon from January 2009 to March 2010. Screw implantation was performed
      during internal fixation for fractures, tumors, and spondylodiscitis of the
      thoracic spine as well as for degenerative lumbar scoliosis. RESULTS: The
      accuracy rate in our work was 89.8 % in the free hand group compared to 98 % in
      the generic 3D navigated group. CONCLUSION: In conclusion, 3D navigation-assisted
      pedicle screw placement is superior to free hand technique in the thoracic spine.

PMID- 23007930
TI  - Weight change, lifestyle, and dietary behavior in the US military's Warrior in
      Transition Units.
AB  - OBJECTIVE: To identify lifestyle factors that may contribute to weight changes
      experienced by Warfighters assigned to Warrior in Transition Units (WTU). DESIGN:
      Multicenter, cross-sectional, descriptive study at 4 military installations (Fort
      Hood, TX; Fort Bliss, TX; Fort Sam Houston, TX; and Fort Gordon, GA).
      Participants completed a self-reported questionnaire regarding environmental,
      social, and dietary lifestyle behaviors. Study participants were recruited and
      data collected from February through July 2009. RESULTS: Four hundred twelve
      wounded Warfighters (97.6% Soldiers) participated; 51% indicated they were
      overweight and 61% desired weight loss. About 51% exceeded a normal body mass
      index (18.5 to 27.4 kg/m2) according to Army height and weight standards. Roughly
      85% of all participants experienced weight change following their injury. Limited
      activity was self-reported as the main reason for weight gain (66.2%), and
      deployment as the main reason for weight loss (21.7%). Lifestyle factors that
      changed included skipping meals, eating snacks, eating at sit-down restaurants,
      performing aerobic and anaerobic physical activity. The majority of participants
      (more than 70%) consume 3 standard meals per day, with 25% reporting that the
      meal typically skipped was breakfast. CONCLUSION: The WTU Soldiers saw themselves
      as overweight, desired to lose weight, and reported several changes in lifestyle
      factors upon entry into the WTU. There is a need for more focused nutrition
      related and physical fitness-oriented interventions to aid Warrior recovery,
      promote rehabilitation, and decrease length of time in the WTU.

PMID- 23007931
TI  - Negative health behavior, a personal responsibility or not?

PMID- 23007932
TI  - Synthetic cannabinoid and cathinone use among US soldiers.
AB  - New hallucinogenic drugs of abuse, known generically as "spice" and "bath salts,"
      have become readily available in the United States. Spice is one of many names
      that refers to a variety of synthetic cannabinoids that act on the body in a way
      similar to delta-9-tetrahydrocannabinol (THC). A large and complex variety of
      synthetic cannabinoids, most often cannabicyclohexanol, JWH-018, JWH-073, or HU
      210, are used in an attempt to avoid the laws that make cannabis illegal, making
      synthetic cannabis a designer drug. Bath salts, on the other hand, is one of many
      names for a group of cathinone-containing hallucinogens that produces
      sympathomimetic effects in its users. Both have become popular among those
      seeking chemical euphorias with decreased chance of detection. Consequently, both
      have become a problem for maintaining mentally fit Soldiers, unit readiness, and
      morale in the US armed forces.

PMID- 23007933
TI  - Relationships among self-reported shoe type, footstrike pattern, and injury
      incidence.
AB  - CONTEXT: Some runners are experimenting with barefoot or minimalist shoe running
      to reduce lower extremity overuse injuries. However, there has been little
      research to examine injury trends associated with barefoot or minimalist shoe
      running. OBJECTIVE: To assess the association of self-reported shoe selection
      with reported foot strike patterns, compare overall injury incidence associated
      with different shoe conditions, and identify differences in injury location
      between different shoe conditions. DESIGN: Retrospective descriptive epidemiology
      survey. METHODS: We recruited 2,509 runners (1,254 male, 1,255 female) aged 18 to
      50 to complete an anonymous online survey. The survey assessed running
      tendencies, footstrike patterns, shoe preferences, and injury history. Reported
      footstrike patterns were compared among 3 shoe groups: traditionally shod,
      minimalist shoes, and barefoot runners. Overall and specific anatomical injury
      incidence was compared between traditionally shod and minimalist shoe-wearing
      runners. We did not include 1,605 runners in the analyses due to incomplete data
      or recent changes in footstrike patterns and/or shoe selection. RESULTS: Shoe
      selection was significantly associated with reported footstrike (chi2 (4df)
      =143.4, P<.001). Barefoot and minimalist runners reported a more anterior
      footstrike than traditionally shod runners. Traditionally shod runners were 3.41
      times more likely to report injuries than experienced minimalist shoe wearers
      (46.7% shod vs 13.7% minimalist, chi2 (1df) =77.4, P<.001, n=888). Minimalist
      shoe wearers also reported fewer injuries at the hip, knee, lower leg, ankle, and
      foot than traditionally shod runners. CONCLUSION: Barefoot and minimalist shoe
      wearers reported a more anterior footstrike than traditionally shod runners.
      Traditionally shod runners were more likely to report injuries of the lower
      extremities than runners who wear minimalist shoes. Additional longitudinal
      prospective research is required to examine injury incidence among various
      footstrike patterns and shoe preferences.

PMID- 23007934
TI  - The effects of BleedArrest on hemorrhage control in a porcine model.
AB  - The purpose of this study was to examine the effectiveness of the hemostatic
      agent BleedArrest compared to control. This was a prospective, experimental
      design employing an established porcine model of uncontrolled hemorrhage. The
      minimum number of animals (n=10 per group) was used to obtain a statistically
      valid result. There were no statistically significant differences between the
      groups (P>.05) indicating that the groups were equivalent on the following
      parameters: activating clotting time, the subject weights, core body
      temperatures, amount of one minute hemorrhage, arterial blood pressures, and the
      amount and percentage of total blood volume. There were significant differences
      in the amount of hemorrhage (P=.033) between the BleedArrest (mean=72, SD+/-72
      mL) and control (mean=317.30, SD+/-112.02 mL). BleedArrest is statistically and
      clinically superior at controlling hemorrhage compared to the standard pressure
      dressing control group. In conclusion, BleedArrest is an effective hemostatic
      agent for use in civilian and military trauma management.

PMID- 23007935
TI  - The effects of QuikClot Combat Gauze on hemorrhage control in the presence of
      hemodilution.
AB  - INTRODUCTION: Although hemostatic agents may be effective at stopping hemorrhage,
      they may fail because of hemodilution from intravenous fluids. The purpose of
      this study was to investigate the effects of QuikClot Combat Gauze (QCG) on
      rebleeding in a class II hemorrhage in the presence of hemodilution in a lethal
      femoral injury. METHODS: This was a prospective experimental, between swine
      subjects design. Pigs were assigned to one of two groups: QCG (n=15) or control
      (n=15). Thirty percent of the pig's blood was exsanguinated and then a 3:1 ratio
      of ringers lactate was administered. A groin injury was created by transecting
      the femoral artery and vein to simulate a battlefield injury and allowed to bleed
      for one minute. After one minute of hemorrhage, proximal pressure was applied to
      the injury, and QCG was placed into the wound followed by standard wound packing.
      The control group underwent the same procedures with the exception of the
      hemostatic agent. For both groups, 5 minutes of direct pressure was applied to
      the wound followed by a standard pressure dressing. Dressings were removed after
      30 minutes, and the amount of hemorrhage was calculated in milliliters for each
      group for a period of 5 minutes. An activated clotting time was used to exclude
      any pigs with coagulation pathology. RESULTS: A multivariate analysis of variance
      indicated that there were no significant differences in the groups relative to
      weight, amount of one minute hemorrhage, fluid deficit replacement, blood volume,
      and the activated clotting time (P>.05) indicating that the groups were
      equivalent on these parameters. A t test indicated that there was significantly
      less bleeding (P=.002) in the QCG group (36 mL+/-112 mL) compared to the control
      group (340 mL+/-297 ml). CONCLUSION: QCG produces a robust clot that can more
      effectively tolerate hemodilution compared to a control group.

PMID- 23007936
TI  - Myofibroma of the mandible: a case report.
AB  - This report describes the case of a male aged 28 years who presented with a chief
      complaint of discomfort and swelling in the mandibular right molar area. An
      incisional biopsy was performed with a preliminary differential diagnosis of
      periodontal abscess, fibrotic lesion, or odontogenic tumor. Subsequent excision
      of the lesion was performed and histologic analysis confirmed the diagnosis of
      myofibroma.

PMID- 23007937
TI  - Dentistry's role in the history of the Walter Reed Army Medical Center.

PMID- 23007938
TI  - Developing an operational casualty estimate in a multinational headquarters to
      inform and drive medical resource allocation.
AB  - This article presents a methodology to construct an operational casualty estimate
      for insurgent clearance operations conducted in 2 districts around Kandahar City
      appropriate for a multinational operational headquarters. It demonstrates how to
      identify relevant and recent historical data to establish a casualty rate, apply
      it against a tactical operational sequence and population at risk to get a daily
      casualty estimate, and compare that estimate to the capacity of the medical
      system. This allows medical planners from any contributing nation to express the
      medical risk and mitigation plan to operational leadership and the commander.

PMID- 23007939
TI  - Strategies to support nurse work reintegration after deployment constructed from
      analysis of army nurses' redeployment experiences.
AB  - Many military nurses find a period of transition is necessary in order to fully
      return to work after deployment. Coworkers and supervisors can be a positive or
      negative force in that transition. Using data from a larger study, evidence-based
      strategies to support nurses who return to nursing work after deployment were
      developed. Having an understanding of what returning nurses say about their
      "coming home" phase can help coworkers and supervisors be a positive force in
      work transition. A table of tasks with explanations is provided to assist
      coworkers and supervisors in facilitating the transition back to noncombat nurse
      work.

PMID- 23007940
TI  - Combat casualty care nursing research and the Joint Combat Casualty Research
      Team.

PMID- 23007941
TI  - Registered nurses as permanent members of medical evacuation crews: the critical
      link.
AB  - Medical evacuation has changed form the experiences of the past decade of combat
      operations. Much of the focus of the medical support in the combat zone is now
      critical care during evacuation, which is, and will continue to be, a very
      successful, life-saving asset. The assignment of Army critical care or trauma
      nurses to medical evacuation units is consistent with the recognition that the
      medical evacuation system is a truly vital asset in the success of today's
      American military. Our NATO allies, and our sister services, rely heavily on the
      availability, reliability, and especially continuity of care of the Arm medical
      evacuation system. It is time to upgrade the system of evacuation and provide our
      Warriors with the greatest possibilities of survival. Army nurses trained in
      critical care and trauma nursing are best suited to provide that continuity of
      care.

PMID- 23007942
TI  - Clinical nurse leader: emerging role to optimize unit level performance.

PMID- 23007943
TI  - Lessons learned small unit postdeployment survey results and analysis.
AB  - The Army Medical Department Lessons Learned Division conducted a survey of small
      unit service members from July through September 2011 to obtain feedback on the
      challenges they faced during recent deployment operations. Personnel assigned to
      selected company-sized units, teams, and detachments that redeployed within the
      past 12 months were asked to complete an online survey of questions regarding
      their predeployment and operational experiences. The results revealed a number of
      variables such as respondents' service component, assigned unit, and geographic
      location that influenced views on the issues. The implications of the findings
      are discussed, along with recommendations for future work designed to collect
      small unit observations, insights, and lessons.

PMID- 23007944
TI  - Distinct functional and structural cerebral abnormalities in eating disorders in
      the light of diagnostic classification systems.

PMID- 23007945
TI  - Maohuoside A acts in a BMP-dependent manner during osteogenesis.
AB  - There has been a strong interest in searching for natural therapies for
      osteoporosis. Epimedium koreanum Nakai is an herb that is commonly used in East
      Asia to treat osteoporosis, and most studies of its activity have focused on its
      major ingredient, icariin. In this study, maohuoside A (MHA), a single compound
      isolated from the E. koreanum, was found to promote osteogenesis in mouse bone
      marrow-derived mesenchymal stem cells. We hypothesise that, if MHA potently
      induces osteogenic differentiation in a bone morphogenetic protein-dependent
      manner, it may be used to broaden the sources for cell transplantation and
      thereby establish more efficient bone regeneration systems. Real-time polymerase
      chain reaction and western blot were used to detect the expression of SMAD4, a
      marker of bone formation. Microcomputed tomography and histomorphometric
      techniques showed that oral treatment with MHA was followed by an increase in the
      bone mineral density of the lumbar vertebrae in mice. This result also indicates
      that MHA may directly activate osteopontin gene transcription. In conclusion, MHA
      seems to enhance the osteogenesis of bone marrow-derived mesenchymal stem cells
      at least partly via bone morphogenetic protein signalling.

PMID- 23007947
TI  - The impact of zero-valent iron nanoparticles upon soil microbial communities is
      context dependent.
AB  - Nanosized zero-valent iron (nZVI) is an effective land remediation tool, but
      there remains little information regarding its impact upon and interactions with
      the soil microbial community. nZVI stabilised with sodium carboxymethyl cellulose
      was applied to soils of three contrasting textures and organic matter contents to
      determine impacts on soil microbial biomass, phenotypic (phospholipid fatty acid
      (PLFA)), and functional (multiple substrate-induced respiration (MSIR)) profiles.
      The nZVI significantly reduced microbial biomass by 29 % but only where soil was
      amended with 5 % straw. Effects of nZVI on MSIR profiles were only evident in the
      clay soils and were independent of organic matter content. PLFA profiling
      indicated that the soil microbial community structure in sandy soils were
      apparently the most, and clay soils the least, vulnerable to nZVI suggesting a
      protective effect imparted by clays. Evidence of nZVI bactericidal effects on
      Gram-negative bacteria and a potential reduction of arbuscular mycorrhizal fungi
      are presented. Data imply that the impact of nZVI on soil microbial communities
      is dependent on organic matter content and soil mineral type. Thereby,
      evaluations of nZVI toxicity on soil microbial communities should consider
      context. The reduction of AM fungi following nZVI application may have
      implications for land remediation.

PMID- 23007948
TI  - Brodifacoum is effective against Norway rats (Rattus norvegicus) in a
      tyrosine139cysteine focus of anticoagulant resistance in Westphalia, Germany.
AB  - BACKGROUND: The tyrosine to cysteine amino acid substitution at location 139 of
      the vkorc1 protein (i.e. tyrosine139cysteine or Y139C) is the most widespread
      anticoagulant resistance mutation in Norway rats (Rattus norvegicus Berk.) in
      Europe. Field trials were conducted to determine the incidence of the Y139C
      mutation at two rat-infested farms in Westphalia, Germany, and to estimate the
      practical efficacy against them of applications, using a pulsed baiting treatment
      regime, of a proprietary bait (KleratTM) containing 0.005% brodifacoum. RESULTS:
      DNA analysis for the Y139C mutation showed that resistant rats were prevalent at
      the two farms, with an incidence of 80.0 and 78.6% respectively. Applications of
      brodifacoum bait achieved results of 99.2 and 100.0% control at the two farms,
      when measured by census baiting, although the treatment was somewhat prolonged at
      one site, possibly owing to the abundance of attractive alternative food.
      CONCLUSION: The study showed that 0.005% brodifacoum bait is fully effective
      against Norway rats possessing the Y139C mutation at the Munsterland focus and is
      likely to be so elsewhere in Europe where this mutation is found. The pulsed
      baiting regime reduced to relatively low levels the quantity of bait required to
      control these two substantial resistant Norway rat infestations. Previous studies
      had shown much larger quantities of bromadiolone and difenacoum baits used in
      largely ineffective treatments against Y139C resistant rats in the Munsterland.
      These results should be considered when making decisions about the use of
      anticoagulants against resistant Norway rats and their potential environmental
      impacts.

PMID- 23007949
TI  - Therapeutic hypothermia for neonatal encephalopathy.
AB  - OPINION STATEMENT: Neonatal Hypoxic-ischemic encephalopathy in full term infants
      has been associated with a high risk for morbidity and mortality. The patho
      physiology of brain injury following hypoxia-ischemia, noted in preclinical
      models, is a cascade of events resulting from excitotoxic and oxidative injury
      culminating in cell death. Hypothermia has been noted to be protective by
      inhibiting various events in the cascade of injury. Major randomized clinical
      trials in neonatal HIE have demonstrated reduction in death and disability and
      continued safety and efficacy of neuroprotection in childhood. There is now
      clinical and imaging evidence for hypothermia as neuroprotection. Hypothermia
      should be offered to term infants with either severe acidosis at birth or
      resuscitation needing continued ventilation and evidence of either moderate or
      severe encephalopathy within 6 hours of birth. The target temperature should be
      33 degrees  to 34  degrees C and duration of cooling should be 72 hours, as per
      the published trials. Rewarming should be slow, at 0.5  degrees C per hour.
      Infants should have serial neurological examinations during and at the end of
      cooling and at discharge. Multiorgan function should be supported and hypocarbia
      should be avoided during ventilator therapy. If available, the amplitude
      integrated EEG should be obtained prior to cooling and following rewarming. All
      infants should have magnetic resonance brain imaging studies within 1 to 2 weeks
      of age. Information from the neurological examination, aEEG and MRI studies will
      be helpful in discussing prognosis with parents. All infants should be followed
      for a minimum of 18 months to evaluate growth parameters and neurodevelopment al
      outcome.

PMID- 23007950
TI  - Overview of therapeutic hypothermia.
AB  - OPINION STATEMENT: Therapeutic hypothermia has proven neuroprotective effects in
      global cerebral ischemia. Indications for hypothermia induction include cardiac
      arrest and neonatal asphyxia. The two general methods of induced hypothermia are
      either surface cooling or endovascular cooling. Hypothermia should be induced as
      early as possible to achieve maximum neuroprotection and edema blocking effect.
      Endovascular cooling has the benefit of shorter time to reach target temperature
      but catheter insertion requires expertise and training, which may be a barrier to
      widespread availability. The optimum method of cooling is yet to be determined
      but a multimodal approach is necessary to address three phases of cooling:
      induction, maintentance, and rewarm. Specifying core practitioners who are well
      versed in established guidelines can help integrate the multidisciplinary team
      that is needed to successfully implement cooling protocols. Reducing shivering to
      make heat exchange more efficient with tighter temperature control enables
      quicker time to target temperature and avoids rewarming which can lead to
      inadvertent increase in intracranial pressure and cerebral edema. Promising
      applications but yet to be determined is whether hypothermia treatment can
      improve outcomes in acute ischemic stroke or traumatic brain injury.

PMID- 23007952
TI  - Identification of natural killer cell receptor genes in the genome of the
      marsupial Tasmanian devil (Sarcophilus harrisii).
AB  - Within the mammalian immune system, natural killer (NK) cells contribute to the
      first line of defence against infectious agents and tumours. Their activity is
      regulated, in part, by cell surface NK cell receptors. NK receptors can be
      divided into two unrelated, but functionally analogous superfamilies based on the
      structure of their extracellular ligand-binding domains. Receptors belonging to
      the C-type lectin superfamily are predominantly encoded in the natural killer
      complex (NKC), while receptors belonging to the immunoglobulin superfamily are
      predominantly encoded in the leukocyte receptor complex (LRC). Natural killer
      cell receptors are emerging as a rapidly evolving gene family which can display
      significant intra- and interspecific variation. To date, most studies have
      focused on eutherian mammals, with significantly less known about the evolution
      of these receptors in marsupials. Here, we describe the identification of 43
      immunoglobulin domain-containing LRC genes in the genome of the Tasmanian devil
      (Sarcophilus harrisii), the largest remaining marsupial carnivore and only the
      second marsupial species to be studied. We also identify orthologs of NKC genes
      KLRK1, CD69, CLEC4E, CLEC1B, CLEC1A and an ortholog of an opossum NKC receptor.
      Characterisation of these regions in a second, distantly related marsupial
      provides new insights into the dynamic evolutionary histories of these receptors
      in mammals. Understanding the functional role of these genes is also important
      for the development of therapeutic agents against Devil Facial Tumour Disease, a
      contagious cancer that threatens the Tasmanian devil with extinction.

PMID- 23007953
TI  - De novo CD5-positive primary cardiac diffuse large B-cell lymphoma diagnosed by
      pleural fluid cytology.
AB  - Primary cardiac lymphomas are exceedingly rare. The presence and extent of the
      intracardiac mass is determined by echocardiography, computed tomography (CT), or
      magnetic resonance imaging (MRI); however, the diagnosis is established by
      endomyocardial biopsy or by pericardial or pleural effusion cytology. We describe
      the pleural effusion cytologic features of a primary cardiac lymphoma in a 55
      year-old woman who presented with progressive shortness of breath, fatigue, mild
      dizziness, dull chest ache, and lower extremity edema. Transthoracic
      echocardiography, CT, and MRI showed a large mass centered in the right atrium
      and extending into the right ventricle, associated with pericardial effusion and
      bilateral pleural effusions. Cytologic examination of the pleural fluid showed
      very large pleomorphic malignant cell, some of which were binucleated and
      multinucleated and had anaplastic features. Flow cytometry showed a kappa
      monotypic population of large cells coexpressing CD5, CD19, and CD20; and
      immunoperoxidase stains performed on the cell block sections showed that the
      large neoplastic cells were positive for CD20, PAX5, CD5, and MUM1 and showed a
      very high proliferation rate (over 90%) by Ki67 staining. The cytologic, flow
      cytometry, and immunohistochemistry findings established the diagnosis of de novo
      CD5-positive primary cardiac diffuse large B-cell lymphoma (DLBCL), anaplastic
      variant, which was confirmed by the subsequent endomyocardial biopsy. This is, to
      the best of our knowledge, the first report of de novo CD5-positive primary
      cardiac diffuse large B-cell lymphoma, and the first report of the anaplastic
      variant of DLBCL diagnosed by effusion cytology.

PMID- 23007954
TI  - No place for novel oral anticoagulants in current treatment of acute coronary
      syndromes.

PMID- 23007955
TI  - Optimal cut-offs for Down syndrome contingent screening in a population of 10,156
      pregnant women.
AB  - STUDY DESIGN: A population of 10,156 pregnant women with singleton pregnancies
      were screened by the integrated test. Risks were retrospectively recalculated for
      contingent test strategies with first step intermediate risk groups defined by
      first trimester upper cut-offs of 1 : 10, 1 : 30, 1 : 50, and 1 : 70 and lower
      cut-offs 1 : 1500, 1 : 1200, 1 : 1100, and 1 : 900. The second trimester high
      risk group was based on a single cut-off of 1 : 250. RESULTS: In the first
      trimester, the detection rate (DR) ranged from 21% (6/29) to 52% (15/29) as the
      high risk first trimester cut-off was changed from 1 : 10 to 1 : 70. The
      corresponding first trimester false positive rate (FPR) increased from 0.2% to
      1.4%. In the second trimester, an additional 21/29 (72%) to 12/29 (41%) affected
      pregnancies could be detected with an additional 1.6% to 2.7% false positives
      when lower first trimester cut-offs of 1 : 900 to 1 : 1500 were used. The best
      results were obtained with the upper first trimester cut-off of 1 : 30 and lower
      first trimester cut-off of 1 : 900, which yielded a rate of women requiring a
      second trimester test of only 12%, with overall DR and FPR of 93% and 2.8%,
      respectively. CONCLUSIONS: Although the study population was relatively small,
      the results confirm the advantage of using contingent screening and suggest
      optimal first trimester cut-offs of 1 : 30 (lower cut-off) and 1 : 900 (upper cut
      off).

PMID- 23007956
TI  - Blood supply to the human sternocleidomastoid muscle and its clinical
      implications for mandible reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: The use of the sternocleidomastoid (SCM) flap for
      reconstructive surgery of the mandible seems to be a practicable although
      underestimated option. STUDY DESIGN: This study was conducted on 15 cadavers that
      had been neoprene-latex injected in the middle and inferior pedicles. METHODS:
      Lengths of the SCM were equally divided into upper, middle, and lower thirds.
      Each third was then subdivided into numbered quadrants. This procedure defined
      six levels in the SCM, each corresponding to two quadrants: one medial and the
      other lateral. For each third of the SCM, the origin of the main pedicles was
      recorded. The quadrants where neoprene-latex was detected were reported in the
      dissection book. RESULTS: The upper third of the SCM muscle was constantly
      supplied by branches of the occipital artery. The middle third of the SCM muscle
      received its blood supply from a branch of the superior thyroid artery (right
      SCM/left SCM: 53%/53%), the external carotid artery (27%/20%), or branches of
      both (20%/27%). The lower third of the muscle was supplied by a branch arising
      from the suprascapular artery (73%/73%), the transverse cervical artery (7%/13%),
      the thyrocervical trunk (13%/13%), or the superficial cervical artery (7%/0%).
      The neoprene-latex injected into the subclavian artery reached the four lower
      levels in all SCMs studied (the middle third of the SCM). In 13% of the SCMs,
      this injection also reached level II (the upper third of the SCM). With a double
      injection (inferior and middle pedicles), levels I and II were reached in 100% of
      the cases. CONCLUSIONS: This study shows that, used alone, the lower pedicle does
      not have the ability to ensure the full vascularization of the SCM muscle. A
      composite flap might be safely raised only if the integrity of both inferior and
      middle pedicles is respected.

PMID- 23007957
TI  - Microbial transformations of antimicrobial quinolones and related drugs.
AB  - The quinolones are an important group of synthetic antimicrobial drugs used for
      treating bacterial diseases of humans and animals. Microorganisms transform
      antimicrobial quinolones (including fluoroquinolones) and the pharmacologically
      related naphthyridones, pyranoacridones, and cinnolones to a variety of
      metabolites. The biotransformation processes involve hydroxylation of methyl
      groups; hydroxylation of aliphatic and aromatic rings; oxidation of alcohols and
      amines; reduction of carboxyl groups; removal of methyl, carboxyl, fluoro, and
      cyano groups; addition of formyl, acetyl, nitrosyl, and cyclopentenone groups;
      and cleavage of aliphatic and aromatic rings. Most of these reactions greatly
      reduce or eliminate the antimicrobial activity of the quinolones.

PMID- 23007958
TI  - Heterogeneity and spatial distribution of bacterial background contamination in
      pulp and process water of a paper mill.
AB  - Identifying the source and the distribution of bacterial contaminant communities
      in water circuits of industrial applications is critical even when the process
      may not show signs of acute biofouling. The endemic contamination of facilities
      can cause adverse effects on process runability but may be masked by the observed
      daily variability. The distribution of background communities of bacterial
      contaminants may therefore be critical in the development of new site-specific
      antifouling strategies. In a paper mill as one example for a full-scale
      production process, bacterial contaminants in process water and pulp suspensions
      were mapped using molecular fingerprints at representative locations throughout
      the plant. These ecological data were analyzed in the process-engineering context
      of pulp and water flow in the facilities. Dispersal limits within the plant
      environment led to the presence of distinct groups of contaminant communities in
      the primary units of the plant, despite high flows of water and paper pulp
      between units. In the paper machine circuit, community profiles were more
      homogeneous than in the other primary units. The variability between sampled
      communities in each primary unit was used to identify a possible point source of
      microbial contamination, in this case a storage silo for reused pulp. Part of the
      contamination problem in the paper mill is likely related to indirect effects of
      microbial activity under the local conditions in the silo rather than to the
      direct presence of accumulated microbial biomass.

PMID- 23007959
TI  - Study on ecdysteroid levels and gene expression of enzymes related to ecdysteroid
      biosynthesis in the larval testis of Spodoptera littoralis.
AB  - We investigated here the ecdysteroid titers and the expression of six genes
      coding for known enzymes of the ecdysteroid biosynthesis in the testes of last
      instar larvae of the pest cotton leafworm, Spodoptera littoralis. We showed that
      the timing of the ecdysteroid profile was the same in testes and in hemolymph,
      with a small peak at day 2 and a large one at day 4 after ecdysis. Ecdysone and
      20-hydroxyecdysone (20E) were detected in both tissues. 20E was the major
      ecdysteroid in testes and in hemolymph from day 4. Interestingly, the gene
      expression of the steroidogenetic enzymes, Neverland, and the five cytochrome
      P450 enzymes encoded by the Halloween genes was confirmed in the testes, and
      varied during the instar. However, from the data obtained so far, we cannot
      conclude that the measured ecdysteroids in the testes result from the activity of
      the genes under study. Indeed, it is suggested that the ecdysone produced
      centrally in the prothoracic glands, could have been transformed into 20E in the
      testes, where Sl-shade is well expressed.

PMID- 23007960
TI  - [Technical feasibility and safety of single port colectomy].

PMID- 23007961
TI  - [Advantage of intraoperative neuromonitoring of the external branch of the
      superior laryngeal nerve].

PMID- 23007962
TI  - Age-related differences in corticospinal excitability during a choice reaction
      time task.
AB  - Age-related declines in central processing may affect corticospinal (CS)
      excitability that underlies the emergence of voluntary responses to external
      stimuli. We used single-pulse transcranial magnetic stimulation (TMS) over the
      primary motor cortex to explore the evolution of CS excitability in 14 young and
      ten elderly healthy right-handed participants. Motor-evoked potentials (MEPs)
      were elicited in the right or left first dorsal interosseus (FDI) during the
      preparatory and premotor periods of a choice reaction time (CRT) task, which
      required selection of left or right index finger responses. Both age groups
      showed significant suppression of CS excitability in the preparatory period.
      However, suppression was generally less pronounced in older than in young adults.
      Moreover, our data indicated that a reduced suppression in the right FDI during
      the preparatory period was associated with longer reaction times (RTs) in older
      adults only. In the premotor period, both age groups demonstrated comparable
      facilitation levels towards movement onset. Our findings indicate that increased
      RTs among older individuals could be directly associated with declines in
      preparatory processes. 

PMID- 23007963
TI  - Impaired secretion of interferons by dendritic cells from aged subjects to
      influenza : role of histone modifications.
AB  - Increased susceptibility to respiratory infections such as influenza is the
      hallmark of advancing age. The mechanisms underlying the impaired immune response
      to influenza are not well understood. In the present study, we have investigated
      the effect of advancing age on dendritic cell (DC) function because they are
      critical in generating robust antiviral responses. Our results indicate that
      monocyte derived DCs from the aged are impaired in their capacity to secrete
      interferon (IFN)-I in response to influenza virus. Additionally, we observed a
      severe reduction in the production of IFN-III, which plays an important role in
      defense against viral infections at respiratory mucosal surfaces. This reduction
      in IFN-I and IFN-III were a result of age-associated modifications in the
      chromatin structure. Investigations using chromatin immunoprecipitation with
      H3K4me3 and H3K9me3 antibodies revealed that there is increased association of
      IFN-I and IFN-III promoters with the repressor histone, H3K9me3 in non-stimulated
      aged DCs compared to young DCs. This was accompanied by decreased association of
      these promoters with activator histone, H3K4me3 in aged DCs after activation with
      influenza. In contrast to interferons, the association of TNF-alpha promoter with
      both these histones was comparable between aged and young subjects.
      Investigations at 48 h suggested that these changes are not stable and change
      with time. In summary, our study demonstrates that myeloid DCs from aged subjects
      are impaired in their capacity to produce IFNs in response to influenza virus and
      that age-associated altered histone expression patterns are responsible for the
      decrease in IFN production.

PMID- 23007964
TI  - In vitro and in vivo inhibition of human Fanconi anemia-associated head and neck
      squamous cell carcinoma by a novel nutrient mixture.
AB  - Head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukemia are the
      major causes of mortality and morbidity in Fanconi anemia (FA) patients. The
      objective of this study was to investigate the antineoplastic activity of a novel
      antineoplastic nutrient mixture (NM) (containing lysine, proline, ascorbic acid
      and green tea extract) in human FA-associated HNSCC (FA HNSCC) in vitro and in
      vivo. The human FA HNSCC cell line, OHSU-974 (Fanconi Anemia Research Fund), was
      cultured in RPMI medium supplemented with 20% FBS and antibiotics. At near
      confluence, cells were treated in triplicate with various concentrations of NM:
      0, 50, 100, 250, 500 and 1,000 ug/ml. Cells were also treated with phorbol 12
      myristate 13-acetate (PMA) to induce matrix metalloproteinase (MMP)-9 activity.
      Cell proliferation was detected by MTT assay, the secretion of MMPs by gelatinase
      zymo-graphy, cell invasion through Matrigel, cell migration by a scratch test and
      morphology by hematoxylin and eosin (H&E) staining. In vivo, athymic male nude
      mice (n=12) were inoculated with 3x106 OHSU-974 cells subcutaneously and randomly
      divided into 2 groups: group A was fed a regular diet and group B a regular diet
      supplemented with 1% NM. Four weeks later, the mice were sacrificed and their
      tumors were excised, weighed and processed for histological analysis. NM
      inhibited the growth of OHSU-974 tumors by 47% and tumor burden by 50%. At lower
      concentrations, NM demonstrated no effect on proliferation, but at 1,000 ug/ml a
      40% toxicity was observed. Zymography revealed the MMP-2 and PMA-induced MMP-9
      secretion. NM suppressed the secretion of both MMPs in a dose-dependent manner,
      with a virtual inhibition at 500 ug/ml. NM inhibited OHSU-974 cell invasion
      through Matrigel in a dose-dependent manner with a complete block at 1,000 ug/ml.
      H&E staining showed no morphological changes below 500 ug/ml. These results
      suggest that NM has potential therapeutic use in the treatment of human FA HNSCC.

PMID- 23007965
TI  - De novo correction of mass measurement error in low resolution tandem MS spectra
      for shotgun proteomics.
AB  - We report an algorithm designed for the calibration of low resolution peptide
      mass spectra. Our algorithm is implemented in a program called FineTune, which
      corrects systematic mass measurement error in 1 min, with no input required
      besides the mass spectra themselves. The mass measurement accuracy for a set of
      spectra collected on an LTQ-Velos improved 20-fold from -0.1776 +/- 0.0010 m/z to
      0.0078 +/- 0.0006 m/z after calibration (avg +/- 95 % confidence interval). The
      precision in mass measurement was improved due to the correction of non-linear
      variation in mass measurement accuracy across the m/z range.

PMID- 23007966
TI  - An unusual clinical presentation of ocular trauma in a child.
AB  - To report an unusual clinical presentation of ocular trauma in a child.
      Observational case report used in this study. A 12 year-old previously healthy
      boy presented with decreased vision and corneal opacity in the right eye
      following a punch in the face three years earlier. At presentation, his vision in
      the right eye was counting fingers. Ophthalmologic examination of the right eye
      revealed paracentral Descemet's membrane detachment and slit-lamp examination
      showed corneal opacity occupying almost 80 % of the corneal surface. In addition,
      there was a corneal white liquid collection communicating with the anterior
      chamber. The contralateral eye was within normal limits. The patient underwent
      penetrating keratoplasty. Bacteriological cultures of the corneal liquid did not
      reveal the presence of germs. The post-operative course was uneventful, the graft
      was clear and there was no evidence of graft rejection or failure. Visual acuity
      in the operated eye was 5/10. At present, the patient is still being followed up.
      The authors believe that this case is unique since Descemet's membrane detachment
      with liquid collection and corneal opacification has never been reported in
      literature to date.

PMID- 23007967
TI  - Secondary intraocular lens interventions: predisposing factors, indications and
      coincident procedures.
AB  - To evaluate the predisposing factors, indications and coincident procedures in
      patients requiring a secondary intraocular lens (IOL)-related intervention. We
      reviewed data on 183 consecutive secondary IOL-related procedures. Information
      collected included demographics, predisposing factors, IOL status, indication for
      surgery, coincident procedures, and final IOL location and fixation method. Of
      the 183 procedures performed, 73 were secondary IOL implantations, 68 were IOL
      exchanges and 42 were IOL repositionings. Predisposing factors were found in 88.6
      % of the cases, the most common being complicated cataract surgery (39.8 %)
      followed by trauma (20.2 %). The most common indications for surgery in the
      anterior chamber IOL and posterior chamber IOL groups were pseudophakic bullous
      keratopathy +/- failed graft (77.2 %) and subluxated IOL (57.53 %), respectively.
      A malpositioned or subluxated lens was found in 47.86 % of all pseudophakic eyes.
      A simultaneous procedure was performed in 67 % of cases, anterior vitrectomy
      being the most common (43.7 %), followed by keratoplasty (35 %). Secondary IOL
      related interventions were associated with predisposing factors, complicated
      cataract surgery being the most common. Patients implanted with anterior chamber
      IOLs seemed to have a more complicated course requiring more complex secondary
      surgeries and associated procedures.

PMID- 23007969
TI  - Fine-needle aspiration findings of metastatic porocarcinoma.

PMID- 23007968
TI  - Catheter-directed continuous thrombolysis following aspiration thrombectomy via
      the ileocolic route for acute portal venous thrombosis: report of two cases.
AB  - Although acute portal venous thrombosis (PVT) is a potentially life-threatening
      complication that occurs after hepatobiliary surgery with portal vein (PV)
      reconstruction or splenectomy, no effective or universal treatments have yet been
      established. Transjugular or transhepatic catheter-directed thrombolysis has
      recently been reported to be effective for treating acute PVT. However, the
      efficiency of this treatment for complete PV occlusion might be limited because a
      poor portal venous flow prevents thrombolytic agents from reaching and dissolving
      thrombi. Moreover, the use of the transjugular or transhepatic route might not be
      suitable in patients who have undergone major hepatectomy or in those with
      ascites due to an increased risk of residual liver injury or intra-abdominal
      bleeding following puncture to the residual liver. We herein describe the cases
      of two patients with almost total PV occlusion caused by massive thrombi that
      formed after hepatobiliary surgery, who were successfully treated with catheter
      directed continuous thrombolysis following aspiration thrombectomy via the
      ileocolic route. This treatment should be considered beneficial for treating
      selected patients such as the two patients described herein.

PMID- 23007970
TI  - The value of ethyl cysteinate dimer single photon emission computed tomography in
      predicting antidepressant treatment response in patients with major depression.
AB  - OBJECTIVE: The purpose of this study is to examine whether the reversal of
      compromised regional cerebral blood flow (rCBF) in older patients with major
      depressive disorder (MDD) is dependent on specific parameters of selective
      serotonin reuptake inhibitor (SSRI) treatment and to examine the efficacy of such
      treatment. METHODS: Forty-five patients with moderate MDD were studied following
      8 weeks of treatment with SSRIs. Twelve patients displayed a positive response to
      SSRIs, whereas 33 patients did not respond to SSRI treatment. A comparison group
      of 30 healthy volunteers was also studied. The age of all participants was
      greater than 50 years. Age, gender, and the Hamilton Rating Scale for Depression
      scores were examined. The rCBF was assessed using 99mTc-ethyl cysteinate dimer
      single photon emission computed tomography after SSRI treatment. RESULTS: The
      rCBF levels in the right middle frontal cortex in non-responsive MDD patients
      were lower compared with responsive MDD patients. Compared with healthy controls,
      non-responders had significantly lower rCBF levels in the bilateral middle
      frontal cortex and insula and had significantly higher rCBF levels in the
      bilateral inferior frontal cortex and left middle temporal cortex. Compared with
      healthy controls, responders had significantly higher rCBF levels in the left
      inferior frontal, middle temporal, precentral, and fusiform gyrus. We found no
      changes in single photon emission computed tomography between pre-treatment and
      post-treatment stages for the responders to SSRI treatment. CONCLUSION:
      Hypoperfusion in older, non-responsive MDD patients was primarily localized in
      the middle frontal cortex. It is possible that the responders to SSRI treatment
      at baseline already displayed higher rCBF values in the frontal regions.

PMID- 23007971
TI  - Comparative  fusion expression of maize SINAT5 in two different strains of
      Escherichia  coli.
AB  - SINAT5  is a plant E3 ligase that regulates auxin signaling and root
      morphogenesis by  ubiquitination of the NAC1 protein. Consequently, it may be a
      putative  regulator of aspects of plant development cycles that are controlled by
      auxin.  Efficient production, purification and correctly folded form of this
      protein  are important requirements for functional studies. We produced and 
      quantitatively compared fusion expression of the "maltose binding protein (mbp)
      maize sinat5" construct in two different strains of Escherichia coli. One-step 
      purification of fused products gave about 33 mg protein/L bacterial cell  culture
      for E. coli TB1 cells and approximately 18 mg protein/L  bacterial cell culture
      for E. coli DH5alpha cells. Continuous expression of the  fused product and
      similarity of growth patterns were observed in both cultures.

PMID- 23007972
TI  - New microsatellite markers for the abalone Haliotis  midae developed by 454
      pyrosequencing and in silico analyses.
AB  - Farming of Haliotis midae is the most lucrative aquaculture venture in South
      Africa. The genome of this species needs to be studied to assist in selective
      breeding programs aimed at increasing overall yield, and molecular markers will
      be required to attain this goal. We identified and characterized 82 polymorphic
      microsatellite loci by using repeat-enriched genomic libraries and high
      throughput pyrosequencing technology. The observed number of alleles ranged from
      2 to 21, expected heterozygosity from 0.063 to 0.968, observed heterozygosity
      from 0.000 to 1.000, and polymorphic information content from 0.059 to 0.934.
      Three loci gave significant hits to other haliotid genes and/or microsatellite
      loci; hits to genes were always located in the 5'/3'-UTR or intron region. Many
      of these newly designed markers would be useful for parentage, population and
      linkage studies.

PMID- 23007973
TI  - Neural-endocrine  mechanisms of respiratory syncytial virus-associated asthma in
      a rat model.
AB  - We  examined the underlying neural-endocrine mechanisms of asthma associated with
      respiratory syncytial virus infection. Thirty Sprague-Dawley rats were randomly 
      divided into control group, respiratory syncytial virus (RSV) group, and  anti
      nerve growth factor (NGF) IgG group. An RSV infection model was  established by
      nasal drip once a week. In the anti-NGF antibody intervention  group, each rat
      was given an intraperitoneal injection of anti-NGF IgG 3 h  before RSV infection.
      Optical microscopy and transmission electron microscopy  were used to observe the
      structural changes in adrenal medulla cells. Changes  in adrenaline and
      norepinephrine in serum were detected by ELISA. NGF  expression was assayed by
      immunohistochemistry. Expression differences in  synaptophysin mRNA were detected
      by RT-PCR. Transmission electron microscopy  displayed widened adrenal medulla
      intercellular spaces, reduced chromaffin  particle concentration, and increased
      mitochondria in the RSV infection group.  At the same time, NGF expression was
      increased in the RSV infection group  significantly. In addition, the adrenaline
      concentration was significantly decreased  compared with the control and anti-NGF
      antibody groups. Synaptophysin mRNA  expression was significantly increased in
      the RSV infection and anti-NGF  antibody groups. However, compared with the RSV
      infection group, synaptophysin  mRNA expression was significantly decreased in
      the anti-NGF antibody group. We  conclude that RSV infection could induce adrenal
      medulla cell differentiation  to nerve cells by over-expression of NGF, resulting
      in the decreased endocrine  function found in asthma progression.

PMID- 23007974
TI  - Combining ability analysis for  within-boll yield components in upland cotton
      (Gossypium hirsutum L.).
AB  - Cotton is an important cash crop worldwide, accounting for a large percentage of
      world agricultural exports; however, yield per acre is still poor in many
      countries, including Pakistan. Diallel mating system was used to identify parents
      for improving within-boll yield and fiber quality parameters. Combining ability
      analysis was employed to obtain suitable parents for this purpose. The parental
      genotypes CP-15/2, NIAB Krishma, CIM-482, MS-39, and S-12 were crossed in
      complete diallel mating under green house conditions during 2009. The F0 seed of
      20 hybrids and five parents were planted in the field in randomized complete
      block design with three replications during 2010. There were highly significant
      differences among all F1 hybrids and their parents. Specific combining ability
      (SCA) variance was greater than general combining ability (GCA) variance for
      bolls per plant (9.987), seeds per boll (0.635), seed density (5.672), lint per
      seed (4.174), boll size (3.69), seed cotton yield (0.315), and lint percentage
      (0.470), showing predominance of non-additive genes; while seed volume (3.84) was
      controlled by additive gene action based on maximum GCA variance. Cultivar MS-39
      was found to be the best general combiner for seed volume (0.102), seeds per boll
      (0.448), and lint per seed (0.038) and its utilization produced valuable hybrids,
      including MS-39 x NIAB Krishma and MS-39 x S-12. The parental line CIM-482 had
      high GCA effects for boll size (0.33) and seeds per boll (0.90). It also showed
      good SCA with S-12 and NIAB Krishma for bolls per plant, with CP- 15/2 for boll
      size, and with MS-39 for seeds per boll. The hybrids, namely, CP-15/2 x NIAB
      Krishma, NIAB Krishma x S-12, NIAB Krishma x CIM-482, MS-39 x NIAB Krishma, MS-39
      x CP-15/2, and S-12 x MS-39 showed promising results. Correlation analysis
      revealed that seed cotton yield showed significant positive correlation with
      bolls per plant, boll size and seeds per boll while it showed negative
      correlation with lint percentage and lint per seed. Seed volume showed
      significant negative correlation with seed density. Seeds per boll were
      positively correlated with boll size and negatively correlated with bolls per
      plant lint percentage and lint per seed. Similarly, lint per seed exhibited
      positive correlation with lint percentage and boll size showed significantly
      negative correlation with bolls per plant. Presence of non-additive genetic
      effects in traits like bolls per plant, seeds per boll, lint per seed, seed
      cotton yield, and lint percentage is indicative of later generation selection or
      heterosis breeding may be adopted. For boll size, seed volume and seed density
      early generation selection may be followed because of the presence of additive
      gene action. The parental material used in this study and cross combinations
      obtained from these parents may be exploited in future breeding endeavors.

PMID- 23007975
TI  - Extract from mistletoe, Viscum  album L., reduces Hsp27 and 14-3-3 protein
      expression and  induces apoptosis in C6 rat glioma cells.
AB  - Extracts  of mistletoe (Viscum album) are intensively used in complementary 
      medicine, but their mechanisms are not fully understood in most cases, and the 
      effects on metabolism have not been investigated in detail. However, some 
      biologically active natural products are well known to provoke unexpected 
      cellular responses. They reduce overexpression of heat shock proteins (Hsps) in 
      cancer cells. The aim of the current study was to determine whether methanolic 
      extract of V. album, which possesses antioxidant activity, has an effect  on
      expression levels of Hsp27 and 14-3-3 proteins in a C6 glioma cell line. For  the
      first time, the apoptosis-inducing effect of this extract was also  determined
      via caspase-3 activation in the cells. Overexpression of Hsps was  induced by
      heat shock at 42 degrees C for 1 h. Expression levels of Hsp27 and 14-3-3 
      proteins were determined using Western blot analysis. The apoptosis-inducing 
      effect was also evaluated via caspase-3 activation in C6 glioma cells. 
      Pretreatment of the cells with a nontoxic dose (100 MUg/mL) of V.  album extract
      before heat shock significantly reduced expression levels of  Hsp27 (73%) and 14
      3-3beta (124%), 14-3-3gamma (23%), and 14-3-3zeta (84%) proteins.  Pretreatment
      with the extract before heat shock increased apoptosis via  caspase-3 activation
      (60%) in C6 glioma cells. This result suggested that the  methanolic extract of
      V. album downregulates expression of Hsp27 and 14-3-3  chaperone proteins and
      induces apoptosis, which warrants further exploration as  a potential bioactive
      compound for cancer therapy.

PMID- 23007976
TI  - Knockdown  expression of Apc11 leads to cell-cycle distribution reduction in G2/M
      phase.
AB  - Anaphase-promoting  complex/cyclosome (APC/C) is a key E3 ubiquitin ligase in
      cell division, which  catalyses ubiquitination of cell-cycle regulators. Studying
      this complex could  reveal important information regarding its application in
      cancer research and  therapy. In this study, 4 synthesized small interfering RNAs
      (siRNAs) were  transfected into HEK293T cells to suppress messenger RNA (mRNA) of
      Apc11; 2 of  these reduced the amount of Apc11 mRNA by over 50%. Further
      experiments showed  that rather than causing apoptosis, siRNA transfection led to
      cell-cycle  distributions characterized by less time spent in G2/M phase and more
      time  spent in G1 phase. This phenomenon was specifically induced by Apc11
      silencing,  as co-transfection of siRNA and an Apc11 plasmid could reverse this 
      distribution bias. Our results suggested that siRNA targeted against Apc11  could
      hamper entry into G2/M phase. Current efforts are focused on elucidating the 
      function and utility of the APC complex for clinical applications.

PMID- 23007977
TI  - Monosomic and  molecular mapping of adult plant leaf rust resistance genes in the
      Brazilian  wheat cultivar Toropi.
AB  - Leaf rust is one of the most destructive diseases affecting wheat worldwide. The
      most effective way to control it is to use resistant cultivars. Resistance based
      on slow-rusting adult plant resistance (APR) genes has proven to be the best
      method for developing cultivars with durable resistance. A source of slow-rusting
      APR for leaf rust is the Brazilian wheat cultivar Toropi. The Toropi/IAC 13 F2
      and F7 recombinant inbred lines (RILs) were developed in previous studies.
      Phenotypic analysis of the F2 and F7 RILs showed that 2 recessive genes that were
      temporarily named trp-1 and trp-2 conferred APR in Toropi. In the present study,
      we used monosomic families and amplified fragment length polymorphism (AFLP),
      sequence-tagged site, and simple sequence repeat (SSR) markers to map trp-1 and
      trp-2 on wheat chromosomes. Analysis of the F2 monosomic RIL showed that trp- 1
      and trp-2 were located on chromosomes 1A and 4D, respectively. AFLP analysis of
      the F7 RIL identified 2 independent AFLP markers, XPacgMcac3 and XPacgMcac6,
      which were associated with Toropi APR. These markers explained 71.5% of the
      variation in the phenotypic data in a multiple linear regression model. The AFLP
      markers XPacg/ Mcac3 and XPacg/Mcac6 were anchored by SSR markers previously
      mapped on the short arms of chromosomes 1A (1AS) and 4D (4DS), respectively. The
      trp-2 gene is the first leaf rust resistance gene mapped on wheat chromosome 4DS.
      The mapping of trp-1 and trp-2 provides novel and valuable information that could
      be used in future studies involving the fine mapping of these genes, as well as
      in the identification of molecular markers that are closely related to these
      genes for marker-assisted selection of this important trait in wheat.

PMID- 23007978
TI  - A method for extracting period~10 modulations from DNA  sequence correlations
      applied to the Drosophila melanogaster genome.
AB  - Nucleosome DNA packaging and positioning within the Drosophila  melanogaster
      genome imposes a weak modulation, with a period of about 10 bp  in the genomic
      composition correlations. We present formalism for extracting  such modulations
      from an irreducible set of six correlation functions  calculated along the D.
      melanogaster genome. These modulations were seen  to be stronger for the
      irreducible self-correlation C(zz)(k)  (strong-weak binding). Using an FFT
      procedure, we show that the period~10  modulation extracted from such self
      correlation is viewed to be an oscillation  with period~10.9 overmodulated by an
      oscillation with period~153. This behavior  of the modulation reflects the
      organization of the eukaryotic genomic DNA. But,  since the period~10 modulation
      dies for k ~150, the constraints  imposed by the nucleosome arrangement over the
      nucleosome sequence composition  must be weak, provided that such constraints are
      the sources for the  modulations.

PMID- 23007979
TI  - Genotoxicity of  the medicinal plant Maytenus robusta in mammalian cells in vivo.
AB  - Plants  belonging to the Celastraceae family have been used in traditional
      medicine for  their analgesic, anti-inflammatory and anti-ulcerogenic properties,
      among  others. Maytenus ilicifolia is the principal species of this family, and 
      is used in the treatment of gastric ulcers. However, owing to its inadequate 
      management in Brazil, the species is becoming extinct and is being substituted 
      with Maytenus robusta, which also displays gastroprotective activity.  The aim of
      this study was to evaluate the genotoxic effects of M. robusta hydroalcoholic 
      extract in vivo, using the comet assay and micronucleus test. Three  doses (50,
      250 and 500 mg/kg body weight) were administered to mice orally 2  times at 24-h
      intervals. Cytotoxicity was assessed by scoring 200 consecutive  total
      polychromatic and normochromatic erythrocytes to calculate their ratio. 
      Parametric (analysis of variance/Tukey) and non-parametric (Kruskal-Wallis/Dunn
      post hoc) tests were used to evaluate the results according to the  nature of the
      data distribution. The results showed a significant increase in  the frequency of
      DNA damage on leukocytes at the 2 higher doses tested, but the  extract did not
      enhance micronucleus frequency in bone marrow cells. Our  findings showed that
      after 48 h of treatment, M. robusta hydroalcoholic  extract had weak genotoxic
      effects but no clastogenic effects in mice cells.

PMID- 23007980
TI  - Inter- and intra-specific genetic  diversity of Iranian yarrow species Achillea
      santolina  and Achillea tenuifolia based on ISSR and RAPD  markers.
AB  - Cultivation  and preservation of yarrow has recently attracted wide attention due
      to its  beneficial properties; however, genetic variation of Achillea species is 
      still relatively unknown. We used RAPD and ISSR markers to assess genetic 
      diversity in 16 accessions of yarrow belonging to two species native to Iran. 
      Seven ISSR and nine RAPD primers generated 187 amplified fragments, of which  159
      were polymorphic. The similarity coefficient among Achillea tenuifolia accessions
      ranged from 61 to 86%, and from 40 to 84% among A. santolina accessions.  A low
      similarity was observed between these two species (mean similarity =  0.36%).
      This low similarity is consistent with their geographical distribution. 
      According to the results of cluster and PCA analyses, the two species  completely
      separated from each other. These markers will aid in the  identification of elite
      genotypes for domestication and breeding programs.

PMID- 23007981
TI  - Stability and  adaptability of popcorn genotypes in the State of Rio de Janeiro,
      Brazil.
AB  - This  study aimed to obtain estimates of stability and adaptability of phase
      launched  materials and materials recommended in the country, for the northern
      and  northwestern regions of Rio de Janeiro State, Brazil, and made a comparative
      analysis of different methods to evaluate stability and adaptability of grain 
      yield and popping expansion. To this end, 10 genotypes were evaluated  (UNB2U-C3,
      UNB2U-C4, BRS Angela, Vicosa, Beija-Flor, IAC 112, IAC 125, Zelia,  Jade, and
      UFVM2 Barao de Vicosa) in five environments. The Yates and Cochran  method
      revealed that genotypes UFV2M Barao de Vicosa, BRS Angela and UNB2U-C3  were the
      most stable for grain yield. This method also indicated superiority of  genotypes
      UNB2U-C3, UNB2U-C4, BRS Angela, Vicosa, IAC 125, and Zelia for  popping
      expansion. The Plaisted and Peterson and Wricke methods demonstrated  that
      genotypes Zelia and UNB2U-C4 were the most productive and stable. These  methods
      indicated genotypes UNB2U-C3 and BRS Angela as the most stable for  popping
      expansion. The Kang and Phan ranking system uses methods based on  analysis of
      variance and classified population UNB2U-C4 as the genotype with  the highest
      stability of grain production and confirmed cultivar BRS Angela as  the most
      stable for popping expansion. Genotypes IAC 112 and UNB2U-C4 were the  most
      stable and adapted for grain yield, according to the Lin and Binns method.  The
      P(i) statistics  also ranked UNB2U-C3 and UNB2U-C4 as the genotypes with the best
      predictability  and capacity for popping expansion.

PMID- 23007982
TI  - Meta-analysis confirms that a  common  G/C variant in the pre-miR-146a gene
      contributes to cancer susceptibility and that ethnicity, gender and smoking
      status are risk factors.
AB  - Evidence  has shown that miR-146a is involved in carcinogenesis, and a common G/C
      variant  (rs2910164) in the pre-miR-146a gene has been associated with various 
      types of cancer. We summarized the data from 22 published case-control studies 
      on the association between rs2910164 and cancer risk and performed subgroup 
      analyses by ethnicity, gender and smoking status. We found a significant 
      association between the pre-miR-146a polymorphism and cancer risk in  Caucasian
      populations (odds ratio (OR) = 0.93, 95% confidence interval (CI) =  0.88-0.99
      for G- vs C-allele), while the significance was borderline in  Asian populations
      (OR = 1.11, 95%CI = 1.00-1.23 for G- vs C-allele). A  significantly increased
      risk of cancer was found in males with GG/GC genotypes  (OR = 1.23, 95%CI = 1.10-
      1.37), and the significance was more pronounced in  smokers (OR = 1.82, 95%CI =
      1.32-2.51) than in non-smokers (OR = 1.24, 95%CI =  1.01-1.53). We conclude that
      there is evidence that the pre-miR-146a polymorphism  contributes to cancer
      susceptibilities and that gender and smoking status  affect the probability of
      cancer in individuals with this polymorphism.

PMID- 23007983
TI  - Expression of growth genes in  response to glycerol use in Japanese quail diets.
AB  - Glycerol  can be used as a substitute for corn for feeding poultry, but there are
      concerns about how it may affect growth performance and health of the birds. We 
      evaluated the expression of mRNA of growth hormone (GH) and insulin-like growth 
      factor I (IGF-I) in 35-day-old Japanese quails fed different glycerol levels  (0,
      4, and 8% dietary glycerol instead of corn). Total RNA was extracted from  the
      breast muscle and cDNA was amplified with the use of specific primers for  these
      genes using real-time PCR. Quails fed the diet with 8% glycerol  supplementation
      had significantly lower GH mRNA and IGF-I mRNA expression than  those fed no
      glycerol or 4% glycerol. No significant effect of the treatments  was found on
      quail weight gain or feed intake. Feed conversion ratio was  influenced by
      dietary glycerol levels: the group fed 8% glycerol displayed the  worst feed
      conversion ratio (2.54) compared with that of quail fed the control  diet (2.35)
      or 4% glycerol (2.36). Considering quail performance and the  expression of the
      genes GH and IGF-I, a level of 4% glycerol can be used in  quail feeding without
      any harmful effects.

PMID- 23007985
TI  - Expression  profiling based on coexpressed modules in obese prepubertal children.
AB  - The  aim of this study was to identify related genes and the underlying molecular
      mechanisms in obese patients who show a series of clinical and metabolic 
      abnormalities known as metabolic syndrome. We identified expression profiles 
      through a coexpression network. In addition, a similarity matrix and expression 
      modules were constructed based on domain and pathway enrichment analysis. The 
      genes in module 1 were mainly involved in the metabolism of xenobiotics by 
      cytochrome P450, aldosterone-regulated sodium reabsorption, and focal adhesion 
      owing to the presence of aldo/ketoreductase, basic helix-loop-helix, von 
      Willebrand factor, Frizzled-related domain, and other domains. The genes in 
      module 3 may be involved in cell cycle (hsa04110) and DNA replication (hsa03030) 
      pathways through mini-chromosome maintenance, serine/threonine protein kinase, 
      the protein kinase domain, and other domains. We analyzed the published 
      molecular mechanisms of obesity and found many genes and pathways that have not 
      been given enough attention and require further confirmation.

PMID- 23007984
TI  - Genetic relationships among five varieties of Curcuma  alismatifolia
      (Zingiberaceae) based on ISSR markers.
AB  - The genus Curcuma is a member of the ginger  family (Zingiberaceae) that has
      recently become popular for use as flowering  pot plants, both indoors and as
      patio and landscape plants. We used PCR-based  molecular markers (ISSRs) to
      assess genetic variation and relationships between  five varieties of curcuma
      (Curcuma alismatifolia) cultivated in  Malaysia. Sixteen ISSR primers generated
      139 amplified fragments, of which 77%  had high polymorphism among these
      varieties. These markers were used to  estimate genetic similarity among the
      varieties using Jaccard's similarity  coefficient. The similarity matrix was used
      to construct a dendrogram, and a  principal component plot was developed to
      examine genetic relationships among  varieties. Similarity coefficient values
      ranged from 0.40 to 0.58 (with a mean  of 0.5) among the five varieties. The mean
      value of number of observed alleles,  number of effective alleles, mean Nei's
      gene diversity, and Shannon's  information index were 8.69, 1.48, 0.29, and 0.43,
      respectively.

PMID- 23007986
TI  - Molecular phylogenetic study of  Cardamine amaraeformis Nakai  using nuclear and
      chloroplast DNA markers.
AB  - The  internal transcribed spacer regions of nuclear ribosomal DNA, trnL and trnL
      F  chloroplast genes of Cardamine amaraeformis Nakai (Brassicaceae) were 
      sequenced and analyzed with the sequences of related Cardamine sp  available in
      GenBank to detect the pattern of C. amaraeformis evolutionary  differentiation.
      C. amaraeformis, which is endemic to South Korea,  formed a clade with Cardamine
      pedata (69 bootstrap support) in all trees  resulting from combined sequence data
      analyses of internal transcribed spacer, trnL  and trnL-F genes. The phylogenetic
      analysis also clearly revealed that C.  amaraeformis is distinct from the
      morphologically similar Cardamine  scutata.

PMID- 23007987
TI  - Construction of the intermediate  vector pVBG2307 by incorporating vital elements
      of expression vectors pBI121 and pBI221.
AB  - Molecular  chaperones of plasmid pBI121 carrying CaMV35S promoter and a
      nucleotide  sequence of plasmid pBI221 were inserted into plasmid pCAMBIA2300 to
      construct  an intermediate vector: pVBG2307. This novel vector pVBG2307 contains
      a greatly  expanded multiple cloning site with an adjacent imported CaMV35S
      promoter  sequence. This vector allows controlled transformation of DNA in both
      Escherichia  coli and Agrobacterium tumefaciens. Cloned PG, orf456, ipt genes and
      E8, a fruiting promoter, were amplified by PCR of  cDNA libraries of Capsicum
      annum and Lycopersicon esculentum and  were then transferred into vector
      pVBG2307. The viability of this vector was  demonstrated, as it regulated PG,
      orf456, ipt and E8 genes  in E. coli and could be transferred into Agrobacterium
      strain  EHA105-4.

PMID- 23007988
TI  - Recombinant  adeno-associated virus BMP-4/7 fusion gene confers ossification
      activity in  rabbit bone marrow stromal cells.
AB  - The  biological effects of transfection of an adeno-associated virus (AAV) vector
      with bone morphogenetic proteins 4 and 7 (BMP-4/7) fusion gene (AAV-BMP-4/7) 
      were determined in rabbit bone marrow stromal cells (BMSCs). BMP-4 and BMP-7 
      genes were obtained through one-step reverse transcriptase polymerase chain 
      reaction from human placental cells. The BMP-4/7 fusion gene was then generated 
      through recombination. Rabbit BMSCs were transfected with the recombinant AAV 
      vectors carrying AAV-BMP-4/7 with multiplicity of infection values. Cell growth 
      curves were drawn to evaluate the biological effects of AAV-BMP-4/7 on cell 
      activity. The transfection efficiency was measured using a 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium  bromide assay. The ossification of cells was
      evaluated by observing alkaline  phosphatase (ALP) and osteocalcin (OC) activity
      after transfection for 7 and 14  days. The cells were then transfected with AAV
      BMP-4/7 and AAV-enhanced green  fluorescent protein. We successfully constructed
      the recombinant  adeno-associated virus with the BMP-4/7 fusion gene. The
      transfection  efficiency of AAV-BMP-4/7 was approximately 72% without significant
      biological  effects on cell activity. Cell ossification was significant after
      transfection  with AAV-BMP-4/7. The 1 x 10(5) vg/cell  multiplicity of infection
      value of transfection efficiency was more than 5 x 10(4) vg/cell  (59.38%).
      Significantly higher ALP and OC activity occurred in the AAV-BMP-4/7 
      transfection groups than in the AAV-enhanced green fluorescent protein groups
      (t(ALP) =  896.88, P < 0.001; t(OC) =  543.24, P < 0.01). The AAV-BMP-4/7 fusion
      gene can highly efficient  transfect rabbit BMSCs cultured in vitro and it has
      significant  ossification activity.

PMID- 23007989
TI  - Co-inheritance of variants/mutations in Malaysian  patients with Crohn's disease.
AB  - Crohn's disease is a chronic, relapsing inflammatory bowel disease; it affects
      the mucosa and deeper layers of the digestive wall. Two Crohn's disease patients
      who carried the JW1 variant and two patients who carried the SNP5 variant were
      investigated for other co-inherited polymorphisms that could influence Crohn's
      disease development. Based on the sequencing results, a homozygous 5'-UTR-59 G to
      A variant in exon 1 (SNP6) was observed in a patient who carried SNP5, while a
      heterozygous SNP6 variant was detected in the other patient who carried SNP5. No
      other associated mutations or polymorphisms were detected in the two patients who
      carried the JW1 variant of the CARD15/NOD2 gene.

PMID- 23007990
TI  - 11beta-hydroxysteroid  dehydrogenase type 1 gene expression is increased in
      ascending aorta tissue of  metabolic syndrome patients with coronary artery
      disease.
AB  - 11beta-hydroxysteroid  dehydrogenase type 1 (11beta-HSD-1)  activity and mRNA
      levels are increased in visceral and subcutaneous adipose  tissues of metabolic
      syndrome subjects. We analyzed 11beta-HSD-1  expression in human epicardial
      adipose (EA) and ascending aorta (AA) tissues of  metabolic syndrome patients and
      examined their contribution to the development  of coronary atherosclerosis. The
      11beta-HSD-1 expression was evaluated by qRT-PCR in EA and  AA tissues of 20
      metabolic syndrome patients with coronary artery disease  (metabolic syndrome
      group) and 10 non-metabolic syndrome patients without  coronary artery disease
      (controls). 11beta-HSD-1 expression was increased in EA and AA tissues  of the
      metabolic syndrome group (4.1- and 5.5-fold, respectively). A  significant
      positive correlation was found between 11beta-HSD-1  expression in EA tissue and
      waist hip ratio and 11beta-HSD-1  expression in AA tissue and body mass index,
      while a negative correlation was  found between 11beta-HSD-1  expression in EA
      tissue and HDL. Expression of CD68, a macrophage marker, was  significantly
      increased in both tissues of the metabolic syndrome group; it was  2-fold higher
      in AA tissue compared to EA tissue in the metabolic syndrome  group. Our findings
      of increased expression of 11beta-HSD-1 and CD68 in AA tissue of the  metabolic
      syndrome group lead us to suggest that they contribute to coronary 
      atherosclerosis in metabolic syndrome. This positive correlation between  obesity
      markers and 11beta-HSD-1  in AA and EA tissues strengthens the evidence that
      11beta-HSD-1 has a  role in metabolic syndrome. To the best of our knowledge,
      this is the first  report showing 11beta-HSD-1  and CD68 expression in AA tissue
      of metabolic syndrome patients. We suggest  that there is tissue-specific
      expression of 11beta-HSD-1 in metabolic syndrome and  associated cardiovascular
      disorders.

PMID- 23007991
TI  - Microdeletions in 16p11.2 and  13q31.3 associated with  developmental delay and
      generalized  overgrowth.
AB  - Chromosome microarray analysis of  patients with developmental delay has provided
      evidence of small deletions or  duplications associated with this clinical
      phenotype. In this context, a 7.1- to  8.7-Mb interstitial deletion of chromosome
      16 is well documented, but within  this interval a rare 200-kb deletion has
      recently been defined that appears to  be associated with obesity, or
      developmental delay together with overgrowth. We  report a patient carrying this
      rare deletion, who falls into the latter  clinical category, but who also carries
      a second very rare deletion in 13q31.3.  It remains unclear if this maternally
      inherited deletion acts as a second copy  number variation leading to pathogenic
      variation, or is non-causal and the true  modifiers are yet to be determined.

PMID- 23007992
TI  - CYP2E1 RsaI and  96-bp insertion genetic polymorphisms associated with risk for
      colorectal  cancer.
AB  - We  investigated a possible association between alcoholism, cigarette smoking, 
      obesity and CYP2E1 RsaI and 96-bp insertion genetic polymorphisms with  risk for
      colorectal cancer (CRC). Patients with CRC (70 women and 61 men) were  matched
      for gender and age to 206 healthy controls. The mean age of the two  groups was
      62 years. Meat intake, cigarette smoking and alcohol drinking were assessed 
      using a specific frequency questionnaire. The body mass index was also 
      calculated. DNA was extracted from peripheral blood; RsaI polymorphism  genotypes
      were evaluated by PCR-RFLP and 96-bp insertion genetic polymorphisms  were
      evaluated by specific primers. The distributions of CYP2E1 RsaI  c1/c1, c1/c2 and
      c2/c2 genotypes were 90.2, 9.2 and 0.6%, respectively, in  controls and 83.9,
      13.7 and 2.4% in CRC cases. Allele c2 was associated with  increased risk for CRC
      [odds ratio (OR) = 1.88, 95% confidence interval (95%CI)  = 1.02-3.45]. The
      CYP2E1 RsaI c2/c2 genotype was associated with an  increased risk for rectal
      cancer (OR = 3.23, 95%CI = 1.26-9.03). The 96-bp  insertion was slightly more
      frequent in the CRC group (9.3 vs 11.4%, P =  0.19), especially in females (6.4
      vs 11.5%, P = 0.34). Smoking, alcohol  drinking or high intake of red meat and
      CYP2E1 polymorphisms were not  associated with increased risk for CRC. The 96-bp
      insertion was marginally more  frequent (P = 0.07) in undernourished CRC
      subjects. We concluded that the risk  for CRC is higher among individuals with
      allele c2. The CYP2E1 RsaI  c2/c2 genotype was associated with an increased risk
      for rectal cancer.

PMID- 23007993
TI  - Diversity among isolates of cowpea severe mosaic virus  infecting cowpeas in
      northeastern Brazil.
AB  - Eleven isolates of cowpea severe mosaic virus (CPSMV),  a member of the genus
      Comovirus, were selected from 50 samples collected  of nine cowpea fields in
      Northeastern Brazil (Piaui, Ceara, Rio Grande do  Norte, Paraiba, Pernambuco,
      Alagoas, Sergipe, Bahia, and Distrito Federal) and  partially sequenced. The RNA1
      partial sequence, corresponding to the helicase,  viral genome-linked protein,
      picornain 3C-like protease, and the RNA-directed  RNA polymerase genes from
      CPSMV, had high identity among isolates, varying from  98 to 100%. No evidence
      was found for intermolecular or intramolecular  recombination. Phylogenetic
      analysis confirmed that the Brazilian CPSMV  isolates are substantially different
      from the CPSMV strain USA. Despite the low  variability found among Brazilian
      CPSMV isolates, there were notable differences  in the symptomatology of infected
      cowpea plants, ranging from mild to moderate.  Previous reports have demonstrated
      an association between CPSMV symptom  determinants and helicase. However, we
      found no correlation between the  helicase mutations and symptoms caused by
      CPSMV. Nevertheless,  all isolates with mutation R to K in the protease provoked
      severe symptoms.  This type of information can provide a foundation for the
      development of  strategies to produce durable resistant cowpea lines. It is
      crucial for  strategies based on DNA sequence-dependent technologies, such as
      inhibition  with RNAi.

PMID- 23007994
TI  - Mineral content  is related to antioxidant and antimutagenic properties of grape
      juice.
AB  - Grape  juices are an important source of food antioxidants. Unfortunately, there
      is  little data about the mineral composition and the antioxidant, mutagenic and 
      antimutagenic activities of grape juice in eukaryote cells. We evaluated the 
      mineral contents (Mg, Ca, Mn, Fe, Cu, Zn, Si, S, Cl) of grape juices, the 
      antioxidant, mutagenic and/or antimutagenic activities of the juices in the 
      yeast Saccharomyces cerevisiae, and looked for a possible association  between
      mineral content and antioxidant, mutagenic and/or antimutagenic  activities of
      juice samples. Eight commercial grape juices, four purple (Bordo  variety) and
      four white (Niagara variety), were evaluated. Most of the minerals  were in
      similar concentrations in purple and white grape juices, except for  calcium and
      copper; purple grapes had more calcium content and white grapes had  more copper
      content. All grape juices had important antioxidant and  antimutagenic activities
      in S. cerevisiae and prevented the oxidative  damage provoked by hydrogen
      peroxide (P < 0.05). Positive correlations (P  < 0.05) were observed between
      antioxidant and antimutagenic activities and  mineral content. In this context,
      we concluded that the grape juices, white and  purple, are an important mineral
      source, and these contents explain, in part,  the important antioxidant and
      antimutagenic activities.

PMID- 23007995
TI  - cDNA, genomic sequence cloning  and overexpression of giant panda (Ailuropoda 
      melanoleuca) mitochondrial ATP synthase ATP5G1.
AB  - The ATP5G1 gene is one of the three genes that encode mitochondrial ATP synthase 
      subunit c of the proton channel. We cloned the cDNA and determined the genomic 
      sequence of the ATP5G1 gene from the giant panda (Ailuropoda  melanoleuca) using
      RT-PCR technology and touchdown-PCR, respectively. The  cloned cDNA fragment
      contains an open reading frame of 411 bp encoding 136  amino acids; the length of
      the genomic sequence is of 1838 bp, containing three  exons and two introns.
      Alignment analysis revealed that the nucleotide sequence  and the deduced protein
      sequence are highly conserved compared to Homo  sapiens, Mus musculus, Rattus
      norvegicus, Bos taurus,  and Sus scrofa. The homologies for nucleotide sequences
      of the giant  panda ATP5G1 to those of these species are 93.92, 92.21, 92.46,
      93.67, and  92.46%, respectively, and the homologies for amino acid sequences are
      90.44,  95.59, 93.38, 94.12, and 91.91%, respectively. Topology prediction showed
      that  there is one protein kinase C phosphorylation site, one casein kinase II 
      phosphorylation site, five N-myristoylation sites, and one ATP synthase c 
      subunit signature in the ATP5G1 protein of the giant panda. The cDNA of ATP5G1
      was transfected into Escherichia coli, and the ATP5G1 fused with the  N
      terminally GST-tagged protein gave rise to accumulation of an expected 40-kDa 
      polypeptide, which had the characteristics of the predicted protein.

PMID- 23007996
TI  - Cloning and prokaryotic expression  of rat homolog of Serpina3n and its
      expression change during  liver regeneration.
AB  - A  strikingly upregulated expressed sequence tag was screened from regenerating 
      rat liver at 8 h in a 0-4-8-12 h short-interval successive partial hepatectomy 
      model from a previous study. In the present study, a full-length open reading 
      frame (ORF) corresponding to this expressed sequence tag was predicted through 
      electronic cloning and was subsequently cloned from an 8-h rat regenerating 
      liver and deposited in GenBank (accession No. HM448398). Sequence analysis of 
      HM448398 and the predicted ORF revealed that the two ORFs may be different 
      transcripts of a gene. The sequence of HM448398 was highly homologous to that  of
      rat Serpina3n, suggesting that it may be a homolog of Serpina3n. The  pGEX-2TK
      prokaryotic expression vector for this ORF was constructed, and the  result of
      sodium dodecyl sulfate polyacrylamide gel electrophoresis manifested  that the
      recombinant expression vector could express the  glutathione-S-transferase-fused
      rat homolog of Serpina3n in an insoluble form  in BL21. The target fusion protein
      was purified with affinity chromatography  and was used as antigen to immunize
      rabbits for the production of polyclonal  antibodies. Immunohistochemistry and
      real-time reverse transcription polymerase  chain reaction analysis revealed that
      the gene was highly expressed in the  priming and termination phases of liver
      regeneration. These findings lay a  solid foundation for further study of roles
      of HM448398 using knock-in and RNA  interference methods during liver
      regeneration.

PMID- 23007997
TI  - Gene expression  and enzymatic activity of pectin methylesterase during fruit
      development and  ripening in Coffea arabica L.
AB  - Coffee  quality is directly related to the harvest and post harvest conditions. 
      Non-uniform maturation of coffee fruits, combined with inadequate harvest,
      negatively  affects the final quality of the product. Pectin methylesterase (PME)
      plays an  important role in fruit softening due to the hydrolysis of methylester
      groups  in cell wall pectins. In order to characterize the changes occurring
      during  coffee fruit maturation, the enzymatic activity of PME was measured
      during  different stages of fruit ripening. PME activity progressively increased
      from  the beginning of the ripening process to the cherry fruit stage. In silico
      analysis  of expressed sequence tags of the Brazilian Coffee Genome Project
      database  identified 5 isoforms of PME. We isolated and cloned a cDNA homolog of 
      PME for further characterization. CaPME4 transcription was analyzed in  pericarp,
      perisperm, and endosperm tissues during fruit development and ripening  as well
      as in other plant tissues. Northern blot analysis revealed increased 
      transcription of CaPME4 in the pericarp 300 days after flowering. Low  levels of
      CaPME4 mRNAs were observed in the endosperm 270 days after  flowering. Expression
      of CaPME4 transcripts was strong in the branches  and lower in root and flower
      tissues. We showed that CaPME4 acts  specifically during the later stages of
      fruit ripening and possibly contributes  to the softening of coffee fruit, thus
      playing a significant role in pectin  degradation in the fruit pericarp.

PMID- 23007998
TI  - Physical and psychological triggers for attacks in Meniere's disease: the patient
      perspective.

PMID- 23008000
TI  - Axonal dysfunction prior to neuropathy onset in type 1 diabetes.
AB  - BACKGROUND: The present study was undertaken to determine whether there were
      changes evident in axonal membrane function prior to the onset of neuropathy in
      patients with type 1 and type 2 diabetes. METHODS: From a cohort of 110
      consecutive referrals, nerve excitability was investigated in 40 diabetic
      patients without clinical evidence of neuropathy (20 type 1 diabetic patients and
      20 type 2 diabetic patients). Groups were matched for gender, disease duration
      and HbA(1c). Studies were also undertaken in two control groups, younger controls
      and older controls, matched for age and gender with the diabetic cohorts.
      RESULTS: Subjects with type 1 diabetes demonstrated significant nerve
      excitability abnormalities when compared with younger normal controls.
      Specifically, type 1 subjects showed a significant reduction at multiple time
      points in both depolarising and hyperpolarising threshold electrotonus.
      Additionally, the relative refractory period was prolonged (type 1, 3.19 ms;
      younger normal controls, 3.0 ms; p < 0.05) and superexcitability was reduced
      (type 1, -23.12%; younger normal controls, -26.37%; p < 0.05), consistent with
      axonal membrane depolarisation. Correlations were identified in type 1 patients
      between disease duration and nerve excitability parameters, including the
      relative refractory period (r = -0.533, p < 0.05). In contrast, only minor non
      specific changes were noted in the type 2 group. DISCUSSION: This study provides
      clear evidence of altered axonal function in patients with type 1 diabetes in the
      absence of clinical neuropathy. These findings suggest that altered axonal
      membrane potential may precede neuropathy onset in type 1 diabetes and as such
      may indicate a window of opportunity to intervene and potentially reverse axonal
      membrane dysfunction before the development of irreversible neuropathy.

PMID- 23008001
TI  - Development of a multiplex allele-specific primer PCR assay for simultaneous
      detection of QoI and CAA fungicide resistance alleles in Plasmopara viticola
      populations.
AB  - BACKGROUND: DNA-based diagnosis has become a common tool for the evaluation of
      fungicide resistance in obligate phytopathogenic fungus Plasmopara viticola.
      RESULTS: A multiplex allele-specific primer PCR assay has been developed for the
      rapid detection of fungicide resistance in P. viticola populations. With this
      assay, a glycine-to-alanine substitution at codon 143 of the P. viticola
      cytochrome b gene, which conferred QoI fungicide resistance, and a glycine-to
      serine substitution at codon 1105 of the P. viticola cellulose synthase gene
      PvCesA3, which conferred CAA fungicide resistance, were detected simultaneously.
      CONCLUSION: It is suggested that the present assay is a reliable tool for the
      rapid and simultaneous detection of QoI and CAA fungicide resistance alleles in
      P. viticola populations. The assay required only 2 h from the sampling of
      symptoms to the detection of resistance alleles to both fungicides.

PMID- 23008002
TI  - Extractive biodecolorization of triphenylmethane dyes in cloud point system by
      Aeromonas hydrophila DN322p.
AB  - The biological treatment of triphenylmethane dyes is an important issue. Most
      microbes have limited practical application because they cannot completely
      detoxicate these dyes. In this study, the extractive biodecolorization of
      triphenylmethane dyes by Aeromonas hydrophila DN322p was carried out by
      introducing the cloud point system. The cloud point system is composed of a
      mixture of nonionic surfactants (20 g/L) Brij 30 and Tergitol TMN-3 in equal
      proportions. After the decolorization of crystal violet, a higher wet cell weight
      was obtained in the cloud point system than that of the control system. Based on
      the results of thin-layer chromatography, the residual crystal violet and its
      decolorized product, leuco crystal violet, preferred to partition into the
      coacervate phase. Therefore, the detoxification of the dilute phase was achieved,
      which indicated that the dilute phase could be discharged without causing dye
      pollution. The extractive biodecolorization of three other triphenylmethane dyes
      was also examined in this system. The decolorization of malachite green and
      brilliant green was similar to that of crystal violet. Only ethyl violet achieved
      a poor decolorization rate because DN322p decolorized it via adsorption but did
      not convert it into its leuco form. This study provides potential application of
      biological treatment in triphenylmethane dye wastewater.

PMID- 23008003
TI  - Anammox start-up in sequencing batch biofilm reactors using different inoculating
      sludge.
AB  - In this study, anammox bacteria were rapidly enriched in sequencing batch biofilm
      reactors (SBBRs) with different inoculations. The activated sludge taken from a
      sequencing batch reactor was used and inoculated to SBBR1, while SBBR2 was seeded
      with stored anaerobic sludge from an upflow anaerobic fixed bed (2-year stored at
      5-15  degrees C). Nitrogen removal performance, anammox activity, biofilm
      characteristics and variation of the microbial community were evaluated. The
      maximum total nitrogen loading rate (NLR) of SBBR1 gradually reached to 1.62
      kgN/(m3/day) with a removal efficiency higher than 88% and the NLR of SBBR2
      reached to 1.43 kgN/(m3/day) with a removal efficiency of 86%. SBBR2 was more
      stable compared to SBBR1. These results, combined with molecular techniques such
      as scanning electron microscope, fluorescence in situ hybridization, and terminal
      restriction fragment length polymorphism, indicated that different genera of
      anammox bacteria became dominant. This research also demonstrates that SBBR is a
      promising bioreactor for starting up and enriching anammox bacteria.

PMID- 23008004
TI  - [Skin and occupational artificial UV-radiation].
AB  - In various areas of professional activity, exposure of skin to ultraviolet
      radiation coming from artificial sources may occur. These UV rays differ from the
      solar UV radiation due to their intensity and spectrum. We review current
      developments with the introduction of statutory exposure limit values for jobs
      with UV radiation from artificial sources, a selection of relevant activities
      with artificial UV exposure and an overview of the occurrence of skin disorders
      and dermatologically relevant skin diseases caused by these specific occupational
      exposures. The latter is relevant for medical advice in occupational dermatology
      and occupational medicine. On the basis of existing studies on welders and
      studies regarding occupations with "open flames" (using the example of the
      glassblower) it is evident that so far no reliable data exist regarding the
      chronic photodamage or the occurrence of UV-typical skin cancers, but instead
      clear evidence exists regarding the regular occurrence of acute light damage in
      these occupations.

PMID- 23008005
TI  - [Psoriasis in children and adolescents. A nationwide physician survey on the
      healthcare situation in Germany].
AB  - BACKGROUND: The aim of the present scientific study is the description of the
      current healthcare situation for children and adolescents with psoriasis in
      Germany. METHODS: Data on psoriasis in children and adolescents (<= 18) was
      obtained from randomly selected dermatologists and pediatricians throughout
      Germany. The participating doctors could include 1-3 patients from the year 2009
      into the study. RESULTS: The response rate to the survey was 9.7% for
      dermatologists and 1.9% for pediatricians. The study shows that psoriatic
      children and adolescents (n = 244) are treated primarily by dermatologists. With
      regard to the therapy approaches, 79.9% of the children and adolescents were
      treated with topical agents, 7.5% with physical modalities and 5.0% with systemic
      agents. CONCLUSION: Psoriasis in childhood and adolescence is treated
      predominantly by dermatologists. Most of the patients were treated with topical
      corticosteroids. Childhood psoriasis is still a therapeutic challenge and further
      studies about the healthcare situation are necessary.

PMID- 23008006
TI  - [In memoriam: Anton Luger (1918-2012)].

PMID- 23008007
TI  - [Eruptive melanocytic nevi during azathioprine therapy in myasthenia gravis].
AB  - While being treated with azathioprine and dexamethasone, a 21-year old man with
      myasthenia gravis suddenly developed rapidly progressing brown macules,
      predominantly on the trunk, palms and soles. We made a diagnosis of eruptive
      melanocytic nevi (EMN). This rare entity can appear after blistering skin
      diseases, in immunocompromised patients, and, in particular, during
      immunosuppressive therapy for autoimmune diseases. Since therapeutic regimens
      including azathioprine have been frequently reported in association with EMN, we
      recommended to our patient a treatment switch to mycophenolic acid to prevent the
      development of more nevi.

PMID- 23008008
TI  - [Radiation-induced Favre-Racouchot disease].
AB  - A 71-year-old man presented with disfiguring skin changes of the nose and cheek.
      The patient had undergone a surgery of a malignant melanoma of the right
      paranasal sinus and then 5 months later received radiation therapy with 60 Gy
      total dose to the endonasal area. Physical examination revealed elastosis, open
      and closed comedones, and cysts in the field of radiation exposure. Taking in
      account the exclusive affection of the irradiated skin, we diagnosed a radiation
      induced Favre-Racouchot disease. We recommended topical treatment with vitamin A
      derivatives in combination with physical comedo extraction.

PMID- 23008009
TI  - [Modern light protection from the view of occupational dermatology].
AB  - UV-light induced skin cancer is being more and more accepted in Germany as an
      occupational disease for several jobs with increased UV-light exposure. Over the
      past 100 years sunscreens with filters against UVB- and UVA-light have been
      developed. Another development is the use of antioxidants such as vitamin E,
      vitamin C and herbal agents for additional photoprotection. The evidence
      supporting these products in their topical and systemic formulation is very
      variable. The recent changes in the recognition of UV-induced skin cancers as
      occupational diseases increases the need for preventive strategies which are
      supported by appropriate clinical studies.

PMID- 23008010
TI  - Invasive sinonasal actinomycosis: case report and literature review.
AB  - Actinomycosis is a rare anaerobic bacterial infection typically caused by
      Actinomyces israelii. Although part of normal flora in the oral cavity, and
      respiratory and digestive tracts, A israelii can give rise to pathologic
      infections most commonly reported in the oral cavity from odontogenic causes. We
      present a rare case of invasive actinomycosis presenting with extensive midface
      destruction involving the maxilla and paranasal sinuses, with mucosal necrosis
      mimicking an aggressive neoplasm. The diagnosis is usually reached only after
      histopathologic analysis showing characteristic sulfur granules with filamentous
      gram-positive, non-acid-fast bacteria. We review the literature on its
      epidemiology, clinical presentation, diagnosis, treatment, and prognosis.

PMID- 23008011
TI  - A confirmatory approach to examining the factor structure of the Strengths and
      Difficulties Questionnaire (SDQ): a large scale cohort study.
AB  - The aim of this study was to examine the factor structure of the Strengths and
      Difficulties Questionnaire (SDQ) using a Structural Confirmatory Factor Analytic
      approach. The Danish translation of the SDQ was distributed to 71,840 parents and
      teachers of 5-7 and 10-12-year-old boys and girls from four large scale cohorts.
      Three theoretical models were examined: 1. a model with five first order factors
      (i.e., hyperactivity/inattention, conduct, emotional, peer problems and
      prosocial), 2. a model adding two internalising and externalising second order
      factors to model 1, and 3. a model adding a total difficulties second order
      factor to model 1. Model fits were evaluated, multi-group analyses were carried
      out and average variance extracted (AVE) and composite reliability (CR) estimates
      were examined. In this general population sample, low risk sample models 1 and 2
      showed similar good overall fits. Best model fits were found when two positively
      worded items were allowed to cross load with the prosocial scale, and cross
      loadings were allowed for among three sets of indicators. The analyses also
      revealed that model fits were slightly better for teachers than for parents and
      better for older children than for younger children. No convincing differences
      were found between boys and girls. Factor loadings were acceptable for all
      groups, especially for older children rated by teachers. Some emotional, peer,
      conduct and prosocial subscale problems were revealed for younger children rated
      by parents. The analyses revealed more internal consistency for older children
      rated by teachers than for younger children rated by parents. It is recommended
      that model 1 comprising five first order factors, or alternatively model 2 with
      additionally two internalising/externalising second order factors, should be used
      when employing the SDQ in low risk epidemiological samples.

PMID- 23008012
TI  - Gingerol-induced hypoxia-inducible factor 1 alpha inhibits human prion peptide
      mediated neurotoxicity.
AB  - Prion diseases are a family member of neurodegenerative disorders caused by the
      accumulation of misfolded-prion proteins (scrapie form of PrP, PrP(Sc)). The
      accumulation of PrP(Sc) in the brain leads to neurotoxicity by the induction of
      mitochondrial-apoptotic pathways. Recent studies implicated gingerol in
      protection against neurodegeneration. However, the basis of the neuroprotection
      in prion disease remains unclear. Thus, we investigated the influence of gingerol
      on prion peptide-induced neuronal damage. Gingerol blocked PrP(106-126)-mediated
      neurotoxicity by protecting mitochondrial function. Moreover, the protective
      effect of gingerol against PrP(106-126)-induced mitochondrial damage was
      associated with hypoxia-inducible factor 1 alpha (HIF-1alpha) expression.
      Gingerol-induced HIF-1alpha expression inhibited the PrP(106-126)-induced
      mitochondrial dysfunction. On the other hand, inhibition of gingerol-induced HIF
      1 alpha expression attenuated the gingerol-mediated neuroprotective effect. Here,
      we demonstrate for the first time that treatment with gingerol prevents prion
      peptide-mediated neuronal cell death and that the neuroprotection is induced by
      HIF-1alpha-mediated signals. This study suggests that treatment with gingerol may
      provide a novel therapeutic strategy for prion-mediated neurotoxicity.

PMID- 23008014
TI  - Global cognition and 8-year survival among Japanese community-dwelling older
      adults.
AB  - OBJECTIVE: We sought to examine the longitudinal relationship between cognitive
      function and all-cause mortality among Japanese community-dwelling older adults,
      using an 8-year prospective cohort study design with mortality surveillance.
      METHODS: A total of 454 men and 386 women, aged 70 years and older, participated
      in the study. The Mini Mental State Examination (MMSE) was administered to assess
      global cognition. The total MMSE score and subscale scores were used as
      independent variables, and age, gender, education level, chronic disease, sensory
      deficit, depressive symptoms, and instrumental activities of daily living were
      used as covariates. RESULTS: During the follow-up period, 191 subjects (139 men
      and 52 women) died, and 64 subjects (31 men and 33 women) moved to a different
      region of Japan and were lost to follow-up. Use of the multivariate Cox
      proportional hazards model, adjusted for potential confounders, showed that
      global cognition was significantly and independently associated with mortality
      (hazard ratio [HR] = 1.59, 95% confidence interval [CI]: 1.14-2.23 and HR = 2.81,
      95% CI: 1.77-4.36 for the middle [24-27 points] and lowest [0-23 points]
      categories, respectively). Among the MMSE subscales, place orientation (HR =
      1.57, 95% CI: 1.09-2.25), calculation (HR = 1.67, 95% CI: 1.18-2.35), and delayed
      recall (HR = 1.42, 95% CI: 1.03-1.96), were also significantly and independently
      associated with mortality. CONCLUSIONS: Our study suggests that among older
      individuals, those with lower levels of cognitive function are more likely to
      have a shorter lifespan compared with those with higher cognitive functioning.

PMID- 23008013
TI  - Proteome variation among Filifactor alocis strains.
AB  - Filifactor alocis, a Gram-positive anaerobic rod, is now considered one of the
      marker organisms associated with periodontal disease. Although there was
      heterogeneity in its virulence potential, this bacterium was shown to have
      virulence properties that may enhance its ability to survive and persist in the
      periodontal pocket. To gain further insight into a possible mechanism(s) of
      pathogenesis, the proteome of F. alocis strains was evaluated. Proteins including
      several proteases, neutrophil-activating protein A and calcium-binding acid
      repeat protein, were identified in F. alocis. During the invasion of HeLa cells,
      there was increased expression of several of the genes encoding these proteins in
      the potentially more virulent F. alocis D-62D compared to F. alocis ATCC 35896,
      the type strain. A comparative protein in silico analysis of the proteome
      revealed more cell wall anchoring proteins in the F. alocis D-62D compared to F.
      alocis ATCC 35896. Their expression was enhanced by coinfection with
      Porphyromonas gingivalis. Taken together, the variation in the pathogenic
      potential of the F. alocis strains may be related to the differential expression
      of several putative virulence factors.

PMID- 23008015
TI  - Early second trimester maternal plasma levels of thrombin-inhibitor complexes and
      subsequent spontaneous preterm delivery.
AB  - OBJECTIVE: Increased thrombin generation has been implicated as a mechanism for
      several obstetric syndromes including preterm birth preceded by preterm labor
      (PTL) and preterm premature rupture of membranes (PPROM). In this study, we
      attempted to determine whether PTL or PPROM are associated with changes in the
      maternal plasma thrombin level during the early second trimester. METHODS: This
      is a case-control study in which maternal thrombin-antithrombin (TAT) III complex
      concentrations at 15-21 weeks were compared between normal controls (n = 85) and
      women subsequently delivering preterm, due to either PTL with intact membranes (n
      = 21) or PPROM (n = 20). Statistical analysis was conducted using non-parametric
      statistics. RESULTS: PTL patients with intact membranes showed non-significant
      differences in median plasma TAT level (110.1 ug/L) compared with the control
      group (107.9 ug/L). Similarly, women destined to deliver preterm because of PPROM
      had non-significantly higher plasma TAT level (134.3 ug/L) than those in the
      control group (107.9 ug/L) (p > 0.05). Logistic regression analysis demonstrated
      that after controlling for confounders including vaginal bleeding, TAT levels
      remained not significantly associated with subsequent spontaneous preterm birth
      (p = 0.27). CONCLUSION: Maternal plasma TAT level is unsuitable as an early
      second trimester predictor of preterm birth preceded by PTL or PPROM.

PMID- 23008016
TI  - Approaches for the optimization of MR protocols in clinical hybrid PET/MRI
      studies.
AB  - Magnetic resonance imaging (MRI) is the examination method of choice for the
      diagnosis of a variety of diseases. MRI allows us to obtain not only anatomical
      information but also identification of physiological and functional parameters
      such as networks in the brain and tumor cellularity, which plays an increasing
      role in oncologic imaging, as well as blood flow and tissue perfusion. However,
      in many cases such as in epilepsy, degenerative neurological diseases and
      oncological processes, additional metabolic and molecular information obtained by
      PET can provide essential complementary information for better diagnosis. The
      combined information obtained from MRI and PET acquired in a single imaging
      session allows a more accurate localization of pathological findings and better
      assessment of the underlying physiopathology, thus providing a more powerful
      diagnostic tool. Two hundred and twenty-one patients were scanned from April 2011
      to January 2012 on a Philips Ingenuity TF PET/MRI system. The purpose of this
      review article is to provide an overview of the techniques used for the
      optimization of different protocols performed in our hospital by specialists in
      the following fields: neuroradiology, head and neck, breast, and prostate
      imaging. This paper also discusses the different problems encountered, such as
      the length of studies, motion artifacts, and accuracy of image fusion including
      physical and technical aspects, and the proposed solutions.

PMID- 23008017
TI  - Modeling and suppression of respiration induced B0-fluctuations in non-balanced
      steady-state free precession sequences at 7 Tesla.
AB  - OBJECT: To develop and evaluate a model for describing the S1 (S+) and S2 (S-)
      phase in the presence of off-resonance frequency fluctuations, and to evaluate
      the performance of a novel interleaved navigator echo scheme. MATERIALS AND
      METHODS: Using the extended phase graph model, a linear phase term was added to
      the evolution of transverse states. An approximation for the total S2 phase was
      derived with one fit parameter taul, which serves as an effective lifetime of the
      S2 signal. The model was evaluated using synthetic and in vivo phase evolution
      data. In addition, a novel interleaved phase correction scheme for the nb-SSFP
      sequence was applied to BOLD-fMRI data, and the number of activated voxels before
      and after phase correction was determined. RESULTS: The phases of S1 and S2
      signals are significantly different from each other. The proposed nb-SSFP phase
      model provided a good description of the measured phase evolution data, and the
      approximate model for the S2 phase provided both at good fit to the data, as well
      as an effective lifetime of the S2 signal. In some subjects the phase
      contribution from older pathways was underestimated. In the BOLD-fMRI data, a
      twofold increase of the number of activated voxels for the S2 signal was
      observed, compared to no correction and a conventional navigator echo method.
      CONCLUSION: The different phase evolution of S1 and S2 signals can be
      qualitatively described by the proposed model, and detrimental phase history
      effects are significant at 7 Tesla when not appropriately corrected.

PMID- 23008018
TI  - Value of image-guided fine-needle aspiration cytology-a study of 500 cases.
AB  - Guided Fine-Needle Aspiration Cytology (FNAC) as the first line investigation is
      not only useful in diagnosis of space occupying lesions but can also help in
      choosing appropriate management. This technique is most useful in diagnosing
      metastasis but is also helpful in excluding malignancy in some cases. Aim of this
      study is to analyze the spectrum of cytological diagnosis, adequacy, and
      clinicoradiological correlation of guided FNAC. The study was carried out in the
      departments of pathology and radiology for a period from January 2000 to November
      2011. All the data were retrieved from hospital medical record section and
      departmental data bank and were analyzed. We have performed a total of 500 FNACs,
      including 234 under CT guidance and 266 under USG guidance. Among the CT-guided
      FNACs, 87.6% (205 cases) had adequate material which included 152 malignant
      cases, 38 inflammatory cases and 15 benign cases. Among the cases under USG,
      91.7% (244 cases) had adequate material comprising of 112 malignant cases, 44
      inflammatory cases, and 88 benign lesions. It was noted that increased number of
      inadequate aspirate was from lesions with smaller size and increased depth. Out
      of total 264 malignant cases diagnosed on FNAC, 160 cases were identified as
      malignant on clinical and radiological findings. Guided FNAC is useful in deep
      seated lesions as well as in suspicious superficial lesions and is a safe
      diagnostic tool. If performed properly and correlated well with clinical and
      radiological findings, FNAC provides correct diagnosis in most cases.

PMID- 23008019
TI  - Weight and patients' decision to undergo cardiac surgery.
AB  - Obese patients are less likely to have cardiac surgery than normal weight
      patients. This could be due to physician or patient decision-making. We undertook
      a qualitative descriptive study to explore the influence of obesity on patients'
      decision-making to have cardiac surgery. Forty-seven people referred for coronary
      artery bypass graft (CABG) surgery were theoretically sampled. Twelve people had
      declined cardiac surgery. Participants underwent in-depth interviews aimed at
      exploring their decision-making process. Data were analyzed using conventional
      content analysis. Though patients' weight did not play a role in their decision,
      their relationship with their cardiologist/surgeon, the rapidity and
      orchestration of the diagnosis and treatment, appraisal of risks and benefits,
      previous experience with other illness or others who had cardiac surgery, and
      openness to other alternatives had an impact. It is possible that there is a lack
      of comfort or acknowledgment by all parties in discussing the influence of weight
      on CABG surgery risks.

PMID- 23008020
TI  - ERK-modulated intrinsic signaling and G(2)/M phase arrest contribute to the
      induction of apoptotic death by allyl isothiocyanate in MDA-MB-468 human breast
      adenocarcinoma cells.
AB  - Allyl isothiocyanate (AITC), a member of the isothiocyanate (ITC) family found in
      a constituent of cruciferous vegetables, possesses anticancer activity and
      induces apoptosis in various types of human cancer cell lines. However, no
      available information showed antitumor effects in human breast adenocarcinoma
      cells. The current study was focused on exploring the mechanisms underlying AITC
      induced apoptosis in MDA-MB-468 human breast cancer cells in vitro. We found that
      AITC reduced the cell number and viability using trypan blue staining with the
      Countess Automated Cell Counter and the MTT assay, respectively. AITC also was
      found to induce apoptotic cell morphological changes by a contrast-phase
      microscope and cell cycle arrest at G(2)/M phase by flow cytometric assay in MDA
      MB-468 cells. Intrinsic apoptosis-associated factors such as caspase-9 and
      caspase-3 activities were performed, and reactive oxygen species (ROS)
      production, loss of mitochondrial membrane potential (?Psim) occurred in AITC
      treated MDA-MB-468 cells. AITC also stimulated mitochondria-related signaling,
      including p-Bcl-2 (Ser-70), cytochrome c and Apaf-1 in MDA-MB-468 cells. We found
      that the p-ERK signal was upregulated in AITC-treated cells. Importantly, NAC (a
      ROS scavenger) and U0126 (an ERK inhibitor) abolished AITC-reduced viability in
      MDA-MB-468 cells. AITC downregulated CDK1 activity and altered the expression of
      G(2)/M phase-modulated associated protein levels by western blotting in MDA-MB
      468 cells. In summary, our findings demonstrated that AITC-promoted G2/M phase
      and AITC-triggered apoptosis correlate with the activation of phosphorylation of
      ERK in MDA-MB-468 cells. AITC is a potential agent for applcation in the
      treatment of human breast cancer.

PMID- 23008021
TI  - Do obesity and/or stripe wear increase ceramic liner fracture risk? An XFEM
      analysis.
AB  - BACKGROUND: Hypothesized risk factors for fracture of ceramic liners include
      impingement, edge-loading, and cup malpositioning. These risk factors are similar
      to those for generation of stripe wear. However, it is unclear whether the
      biomechanical conditions contributing to stripe wear generation also increase the
      risk for ceramic liner fracture QUESTIONS/PURPOSES: We asked whether (1) head
      stripe wear propensity; and (2) cup orientation would correlate with alumina
      liner fracture risk for instances of normal and elevated body weight. METHODS: An
      eXtended Finite Element Method (XFEM) model was developed to investigate these
      mechanisms. Liner fracture risk for 36-mm alumina bearings was studied by
      simulating two fracture-prone motions: stooping and squatting. Twenty-five
      distinct cup orientations were considered with variants of both acetabular
      inclination and anteversion. Four separate body mass indices were considered:
      normal (25 kg/m(2)) and three levels of obesity (33, 42, and 50 kg/m(2)).
      Material properties were modified to simulate alumina with and without the
      presence of dispersed microflaws. The model was validated by corroboration with
      two previously published ceramic liner fracture studies. RESULTS: Of 200 XFEM
      simulations with flaw-free alumina, fracture occurred in eight instances, all of
      them involving obesity. Each of these occurred with cups in <= 37 degrees 
      inclination and in 0 degrees  anteversion. For 200 corresponding simulations with
      microflawed alumina, fracture propensity was greatest for cups with higher (edge
      loading-associated) scraping wear. Fracture risk was greatest for cups with lower
      inclination (average 42 degrees  for fractured cases versus 48 degrees  for
      nonfractured cases) and lower anteversion (9 degrees  versus 20 degrees ).
      CONCLUSIONS: Fracture propensity for 36-mm liners was elevated for cups with
      decreased anteversion and/or inclination and under conditions of patient obesity.
      CLINICAL RELEVANCE: Factors causing stripe wear, including obesity and cup
      malpositioning, also involve increased risk of ceramic liner fracture and merit
      heightened concern.

PMID- 23008022
TI  - Primary osseous tumors of the hindfoot: why the delay in diagnosis and should we
      be concerned?
AB  - BACKGROUND: Bony tumors of the foot account for approximately 3% of all osseous
      tumors. Diagnosis is frequently delayed as a result of lack of clinician
      familiarity and as a result of their rarity. The reasons for the delays, however,
      are unclear. QUESTIONS/PURPOSES: We therefore determined (1) how hindfoot tumors
      present and the specific reasons for delay in diagnosis; (2) whether the spectrum
      of disease varies between the talus and calcaneus; and (3) how these patients
      were treated. METHODS: We retrospectively reviewed the medical notes and imaging
      for all patients with 34 calcaneal and 23 talar tumors recorded in the Scottish
      Bone Tumour Registry. Demographics, presentation, investigation, histology,
      management, recurrence, and mortality were recorded. RESULTS: Hindfoot tumors
      present with pain and often swelling around the heel (calcaneus) or ankle
      (talus), most often misdiagnosed as soft tissue injury. Calcaneal lesions were
      more likely to be malignant than talar lesions: 13 of 34 versus three of 23.
      CONCLUSIONS: Clinicians should be aware that hindfoot tumors can be initially
      misdiagnosed as soft tissue injuries and suspicion of a tumor should be raised in
      the absence of trauma or persistent symptoms. Lesions affecting the calcaneus are
      more likely to be malignant. Early diagnosis and adjuvant therapy are important.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 23008023
TI  - Widespread osteonecrosis in children with leukemia revealed by whole-body MRI.
AB  - BACKGROUND: Confirmation of early long-bone epiphyseal osteonecrosis in pediatric
      patients with leukemia allows for medical and surgical intervention before
      articular surface collapse. MRI detects early osteonecrosis, but multiple focused
      MR images are required to capture all lesions. QUESTIONS/PURPOSES: We determined
      whether whole-body MRI (WB-MRI) could (1) assist in diagnosing long-bone
      epiphyseal and other osteonecroses, (2) characterize articular surface
      involvement, and (3) detect preferential sites for osteonecrosis. PATIENTS AND
      METHODS: We retrospectively reviewed prospectively collected data on all 11
      pediatric patients newly diagnosed with leukemia who had musculoskeletal pain
      develop that persisted 4 weeks or more during leukemia treatment. All were
      screened for osteonecrosis by WB-MRI, which consisted of a one-time scan of the
      entire body. Osteonecrosis was defined as circumscribed lesions with a distinct
      rim of low signal intensity in the normally high-intensity marrow on T1-weighted
      images and high signal intensity in the normally low-intensity marrow on short
      tau inversion recovery images. RESULTS: WB-MRI confirmed osteonecrosis in nine of
      11 patients. All patients had multisite lesions; eight had long-bone epiphyseal
      lesions, which comprised 66 of 129 (51%) of all lesions. Osteonecrosis involving
      greater than 50% of the epiphyseal surface was present in 57% of distal femoral
      and proximal tibial lesions. All humeral and femoral head lesions involved more
      than 1/3 of the medial surface volume but were asymptomatic. No articular
      collapse was present. All osteonecrotic lesions were more common in the lower
      extremities. CONCLUSIONS: WB-MRI confirmed early epiphyseal osteonecrosis, with
      quantification of articular surface involvement. Lower limbs were preferentially
      affected, but asymptomatic humeral head osteonecrosis was present in five of nine
      patients. LEVEL OF EVIDENCE: Level IV, diagnostic study. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 23008024
TI  - Less invasive rotational acetabular osteotomy for hip dysplasia.
AB  - BACKGROUND: Broad dissection with a long skin incision and detachment of the
      gluteus medius muscle performed for rotational acetabular osteotomy (RAO) can
      result in weakness in abduction strength of the hip. We use a surgical procedure
      for RAO that minimizes operative invasion of soft tissue and reduces incision
      length compared with conventional procedures. QUESTIONS/PURPOSES: We evaluated
      the clinical results of this less-invasive RAO comparing it with the more
      invasive prior procedure with respect to improvement in clinical hip scores and
      radiographic coverage and overall hip survival after the procedure. METHODS: In
      this less-invasive exposure, the medial gluteus muscle is retracted to expose the
      ilium without detachment from the iliac crest. Similarly, the rectus femoris
      muscle tendon is retracted, not excised. The lateral part of the osteotomized
      ilium is cut to form the bone graft instead of harvesting it from the outer
      cortical bone of the ilium. Between 2000 and 2009, 62 patients (71 hips)
      underwent this procedure. Twenty-eight hips had early-stage osteoarthritis and 43
      had advanced-stage osteoarthritis. Mean patient age was 40 years at the time of
      surgery. We evaluated improvement in hip scores (Merle d'Aubigne-Postel, Japanese
      Orthopaedic Association) and radiographic appearance (lateral center-edge angle,
      Sharp's angle, acetabular head index [AHI]). Kaplan-Meier survivorship analysis
      was performed. Mean followup was 5 years (range, 2.0-10.4 years). RESULTS:
      Clinical hip scores improved postoperatively. On average, lateral center-edge
      angle, Sharp's angle, and AHI improved by 38 degrees , 11 degrees , and 42%,
      respectively. Predicted 10-year survival rates were 100% and 72% for hips with
      early- and advanced-stage osteoarthritis, respectively. CONCLUSIONS: In hips with
      early-stage osteoarthritis treated by this less-invasive approach, no progression
      of osteoarthritis was documented and Trendelenburg gait was avoided. However,
      further investigation is necessary for hips with advanced-stage osteoarthritis.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 23008025
TI  - Have bilateral total knee arthroplasties become safer? A population-based trend
      analysis.
AB  - BACKGROUND: Studies suggest a trend in the selection of younger and healthier
      individuals to undergo bilateral TKAs in an attempt to diminish the incidence of
      complications. It remains unclear whether this development has reduced overall
      perioperative morbidity and mortality. QUESTIONS/PURPOSES: We investigated
      whether changes in demographics and comorbidity patterns of patients undergoing
      bilateral TKAs are detectable and coincide with changes in length and cost of
      hospitalization, incidence of perioperative complications, morbidity, and
      mortality. METHODS: We accessed Nationwide Inpatient Survey data files between
      1999 and 2008. One-year periods were created and changes in demographics, length
      of in-hospital stay, and perioperative morbidity and mortality were analyzed.
      RESULTS: An estimated 258,524 bilateral TKAs were performed between 1999 and 2008
      in the United States. The number of annual procedures increased from 19,288 to
      33,679 (75%). Length of hospital stay decreased from 4.98 to 4.01 days. Absolute
      in-hospital mortality rates decreased at an average rate of 10% per year. The
      unadjusted percent and adjusted incidence per 1000 inpatient days decreased from
      0.42% and 0.85 to 0.16% and 0.39. Although the unadjusted incidence of pneumonia,
      pulmonary embolism, and nonmyocardial infarction cardiac complications did not
      change, an increase with time was detectible after adjustment for length of stay.
      No changes in adjusted incidence were seen for other complications. CONCLUSIONS:
      Although a decreased incidence was seen for some major complications, others
      either remained unchanged or had an increased incidence when adjusted for length
      of stay. Future interventions should focus on reducing perioperative risk to
      improve patient safety.

PMID- 23008026
TI  - Genetic engineering of juvenile human chondrocytes improves scaffold-free mosaic
      neocartilage grafts.
AB  - BACKGROUND: Current cartilage transplantation techniques achieve suboptimal
      restoration and rely on patient donor cells or living grafts of chondrocytes.
      PURPOSE: We sought to enhance allogeneic grafts by testing mosaics of genetically
      engineered and naive juvenile human chondrocytes (jCh). METHODS: We obtained
      specimens from three humans and performed three experiments (two in vitro, one in
      vivo). We compared neocartilage with and without (1) supplemented serum-free
      medium (chondrocyte differentiation medium [CDM]), (2) adenoviral BMP-2 (AdBMP-2)
      transduction, and (3) varying ratios (0.1-1) of transduced and naive jCh. We
      compared (4) healing with mosaic grafts with naive neocartilage or marrow
      stimulation in immunosuppressed rats. For each of 10 in vitro treatment groups,
      we had six replicates for each human, and for each of three in vivo treatment
      groups, we had four replicates for one human. We scored the histology with the
      semiquantitative Bern score. RESULTS: AdBMP-2 and naive neocartilage growth in
      CDM were histologically superior (Bern score, 5.2 versus 3.7; 8.0 versus 1.8) and
      size (8.0 versus 6.1; 7.9 versus 2.2 mg) to standard medium. In CDM, AdBMP-2
      decreased viability (76% versus 90%), but increased BMP-2 production (619 ng/mL
      versus 43 pg/mL). Ten percent and 25% AdBMP-2 transduction had Bern scores of 6.8
      and 6.5 and viability of 84% and 83%, respectively. Twenty-five percent mosaic
      grafts provided better healing histologically than marrow stimulation or naive
      neocartilage. CONCLUSIONS: Low-level AdBMP-2 and CDM augment neocartilage
      parameters in vitro and vivo. CLINICAL RELEVANCE: Genetic augmentation of jCh and
      creation of mosaic neocartilage may improve graft viability and articular healing
      compared with naive neocartilage.

PMID- 23008027
TI  - Can a less radical surgery using photodynamic therapy with acridine orange be
      equal to a wide-margin resection?
AB  - BACKGROUND: Wide-margin resections are an accepted method for treating soft
      tissue sarcoma. However, a wide-margin resection sometimes impairs function
      because of the lack of normal tissue. To preserve the normal tissue surrounding a
      tumor, we developed a less radical (ie, without a wide margin) surgical procedure
      using adjunctive photodynamic therapy and acridine orange for treating soft
      tissue sarcoma. However, whether this less radical surgical approach increases or
      decreases survival or whether it increases the risk of local recurrence remains
      uncertain. QUESTIONS/PURPOSES: We determined the survival, local recurrence, and
      limb function outcomes in patients treated with a less radical approach and
      adjunctive acridine orange therapy compared with those who underwent a
      conventional wide-margin resection. METHODS: We treated 170 patients with high
      grade soft tissue sarcoma between 1999 and 2009. Fifty-one of these patients
      underwent acridine orange therapy. The remaining 119 patients underwent a
      conventional wide-margin resection for limb salvage surgery. We recorded the
      survival, local recurrence, and functional score (International Society of Limb
      Salvage [ISOLS]) score) for all the patients. RESULTS: The 10-year overall
      survival rates in the acridine orange therapy group and the conventional surgery
      group were 68% and 63%, respectively. The 10-year local recurrence rate was 29%
      for each group. The 5-year local recurrence rates for Stages II, III, and IV were
      8%, 36%, and 40%, respectively, for the acridine orange group and 13%, 27%, and
      33%, respectively, for the conventional surgery group. The average ISOLS score
      was 93% for the acridine orange group and 83% for the conventional therapy group.
      CONCLUSION: Acridine orange therapy has the potential to preserve limb function
      without increasing the rate of local recurrence. This therapy may be useful for
      eliminating tumor cells with minimal damage to the normal tissue in patients with
      soft tissue sarcoma. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of the levels of evidence.

PMID- 23008028
TI  - Editorial: CORR(r) criteria for reporting meta-analyses.

PMID- 23008030
TI  - Trials, tribulations and speculation! Report from the 7th Biennial Hatter
      Cardiovascular Institute Workshop.

PMID- 23008029
TI  - Immunogenicity of botulinum toxins.
AB  - Botulinum neurotoxins are formulated biologic pharmaceuticals used
      therapeutically to treat a wide variety of chronic conditions, with varying
      governmental approvals by country. Some of these disorders include cervical
      dystonia, post-stroke spasticity, blepharospasm, migraine, and hyperhidrosis.
      Botulinum neurotoxins also have varying governmental approvals for cosmetic
      applications. As botulinum neurotoxin therapy is often continued over many years,
      some patients may develop detectable antibodies that may or may not affect their
      biological activity. Although botulinum neurotoxins are considered "lower risk"
      biologics since antibodies that may develop are not likely to cross react with
      endogenous proteins, it is possible that patients may lose their therapeutic
      response. Various factors impact the immunogenicity of botulinum neurotoxins,
      including product-related factors such as the manufacturing process, the
      antigenic protein load, and the presence of accessory proteins, as well as
      treatment-related factors such as the overall toxin dose, booster injections, and
      prior vaccination or exposure. Detection of antibodies by laboratory tests does
      not necessarily predict the clinical success or failure of treatment. Overall,
      botulinum neurotoxin type A products exhibit low clinically detectable levels of
      antibodies when compared with other approved biologic products. This review
      provides an overview of all current botulinum neurotoxin products available
      commercially, with respect to the development of neutralizing antibodies and
      clinical response.

PMID- 23008031
TI  - Foreground.

PMID- 23008032
TI  - Vitamin A in nature.

PMID- 23008033
TI  - Methods of analysis.

PMID- 23008034
TI  - Food sources.

PMID- 23008035
TI  - Bioavailability of carotenoids.

PMID- 23008036
TI  - Vitamin A in health.

PMID- 23008037
TI  - Assessment of vitamin A status.

PMID- 23008038
TI  - Xerophthalmia.

PMID- 23008039
TI  - Mortality and morbidity, especially in relation to infections.

PMID- 23008040
TI  - Other effects of VAD.

PMID- 23008042
TI  - Global occurrence.

PMID- 23008041
TI  - Interaction of vitamin A and other micronutrients.

PMID- 23008043
TI  - Epidemiology.

PMID- 23008044
TI  - Retinoids and carotenoids in general medicine.

PMID- 23008045
TI  - Control.

PMID- 23008047
TI  - Manual on Vitamin A Deficiency Disorders (VADD). Foreword.

PMID- 23008048
TI  - Manual on Vitamin A Deficiency Disorders (VADD). Preface.

PMID- 23008050
TI  - Birth weight influences the clinical phenotype and the metabolic control of
      patients with type 1 diabetes (T1D).
AB  - BACKGROUND: High birth weight has been related to an increased risk of type 1
      diabetes (T1D), while suboptimal birth weight (both high and low) has been
      related to obesity, insulin resistance and type 2 diabetes. Insulin resistance,
      as a consequence of poor metabolic control, has been described in T1D patients.
      The aims of the study were to analyse the distribution of birth size for
      gestational age in a large group of T1D patients and to investigate the effect of
      birth weight on clinical phenotype. METHODS: Six-hundred two Caucasian T1D
      patients were evaluated. Small for gestational age (SGA) and large for
      gestational age (LGA) were defined as birth weight at <3rd percentile and >97th
      percentile for gestational age, respectively. Birth weights between the 3rd and
      97th percentiles were defined as appropriate for gestational age. The clinical
      characteristics of small, appropriate for gestational age and large were
      compared. Multivariable linear regression models were fitted to evaluate the
      independent effects of birth weight and other covariates (age at T1D onset,
      gender and T1D duration) on different clinical outcomes (body mass index,
      HbA(1c), insulin requirement, high-density lipoprotein cholesterol and
      triglycerides). RESULTS: Thirteen subjects (2.16%) were small (SGA), and 39
      (6.48%) were large (LGA). Daily insulin requirement (U/kg/day) was significantly
      higher in SGA, while body mass index and HbA(1c) were increased in LGA.
      Multivariable linear regression showed a significant negative effect of birth
      weight on daily insulin requirement (p < 0.001). CONCLUSIONS: Suboptimal birth
      weight (both high and low) in T1D patients seems to be associated with clinical
      characteristics suggestive of insulin resistance.

PMID- 23008049
TI  - Projected future increase in aging hepatitis C virus-infected liver transplant
      candidates: a potential effect of hepatocellular carcinoma.
AB  - In the United States, the peak hepatitis C virus (HCV) antibody prevalence of 4%
      occurred in persons born in the calendar years 1940-1965. The goal of this study
      was to examine observed and projected age-specific trends in the demand for liver
      transplantation (LT) among patients with HCV-associated liver disease stratified
      by concurrent hepatocellular carcinoma (HCC). All new adult LT candidates
      registered with the Organ Procurement and Transplantation Network for LT between
      1995 and 2010 were identified. Patients who had primary, secondary, or text field
      diagnoses of HCV with or without HCC were identified. There were 126,862 new
      primary registrants for LT, and 52,540 (41%) had HCV. The number of new
      registrants with HCV dramatically differed by the age at calendar year, and this
      suggested a birth cohort effect. When the candidates were stratified by birth
      year in 5-year intervals, the birth cohorts with the highest frequency of HCV
      were as follows (in decreasing order): 1951-1955, 1956-1960, 1946-1950, and 1941
      1945. These 4 birth cohorts, spanning from 1941 to 1960, accounted for 81% of all
      new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC
      occurred between the calendar years 2000 and 2010 in the 1941-1960 birth cohorts.
      By 2015, we anticipate that an increasing proportion of new registrants with HCV
      will have HCC and be >=60 years old (born in or before 1955). In conclusion, the
      greatest demand for LT due to HCV-associated liver disease is occurring among
      individuals born between 1941 and 1960. This demand appears to be driven by the
      development of HCC in patients with HCV. During the coming decade, the projected
      increase in the demand for LT from an aging HCV-infected population will
      challenge the transplant community to reconsider current treatment paradigms.

PMID- 23008051
TI  - In vivo 3D spatial/1D spectral imaging by spatiotemporal encoding: a new single
      shot experimental and processing approach.
AB  - A novel method for acquiring and processing quality multislice spectroscopically
      resolved 2D images in a single shot is introduced and illustrated. By contrast to
      the majority of single-scan spectroscopic imaging sequences developed so far, the
      method here discussed is not based on the acquisition of echo planar data in the
      k/t-space, but rather on the use of recently proposed spatiotemporal encoding
      methods. These techniques provide a robust alternative to classical techniques,
      as they can scan two spatial plus one spectral dimension by oscillating a single
      imaging gradient. This work demonstrates that the use of extended
      spectral/spatial super-resolution algorithms coupled to new experimental
      spatiotemporal encoding formulations based on swept inversions rather than on
      chirped excitations can lead to novel spatiotemporal encoding-based tools for
      resolving complex multisliced 2D images according to the chemical shifts in
      subsecond experiments. A number of phantom-based models were explored to clarify
      the relative merits of this technique and estimate its sensitivity performance.
      In vivo results of fat and water separation on abdominal imaging of mice at 7 T
      and on human breast imaging at 3 T are presented.

PMID- 23008053
TI  - Sexual orientation disparities in history of intimate partner violence: results
      from the California health interview survey.
AB  - Few studies have examined history of intimate partner violence (IPV) among sexual
      minorities. We assessed prevalence and predictors of IPV using a probability
      sample of California residents ages 18 to 70. Lifetime and 1-year IPV prevalence
      was higher in sexual minorities compared with heterosexuals but this was
      significant only for bisexual women and gay men. IPV of bisexual women, but not
      gay men, occurred in a heterosexual relationship. We tested whether the higher
      prevalence of IPV in gay men and bisexual women was explained by two mental
      health indicators--psychological distress and binge drinking--but this hypothesis
      was not supported.

PMID- 23008052
TI  - Physical domestic violence and subsequent contraceptive adoption among women in
      rural India.
AB  - This study examines the relationship between male to female physical domestic
      violence and contraceptive adoption among women in four economically and
      culturally distinct areas of India. Data from India's 1998-1999 National Family
      Health Survey-2 and a follow-up survey in 2002-2003 for which the same women in
      four states were reinterviewed are analyzed. The focus of the analysis is on how
      baseline exposure to physical domestic violence is associated with the
      intersurvey adoption of contraception. Women who experience physical violence
      from their husbands are significantly less likely to adopt contraception in the
      intersurvey period, although this relationship varies by State. This study builds
      upon previous work by using an indicator of physical domestic violence exposure
      that is measured before contraceptive adoption, thus allowing the identification
      of how exposure to violence shapes the adoption of contraception. The results
      demonstrate that for women living in Bihar and Jharkhand there is a clear
      negative relationship between physical domestic violence and a woman's adoption
      of contraception; this relationship was not found for women in Maharashtra and
      Tamil Nadu. The results point to the need to include domestic violence screening
      and referral services into family planning services.

PMID- 23008054
TI  - Directors' opinions about domestic violence and sexual assault service strategies
      that help survivors.
AB  - Little evidence is available regarding recommended practices for domestic
      violence and sexual assault services. Although there is a literature concerned
      with these services, few studies have investigated recommended practices from the
      perspective of community providers. In addition, researchers have not yet
      investigated the utility of specific domestic violence and sexual assault service
      delivery strategies. To help address these knowledge needs, the authors
      investigated agency directors' perspectives on six types of services typically
      offered by domestic violence and sexual assault agencies including crisis, legal
      advocacy, medical advocacy, support group, individual counseling, and shelter.
      The authors also examined the extent to which directors' opinions about service
      delivery practices differed based on key agency's characteristics, specifically
      the services offered (i.e., domestic violence, sexual assault, or both) and
      agency location (i.e., rural, suburban, or urban). A sample of 97 (94% response
      rate) North Carolina agency directors completed a survey on recommended service
      delivery practices. The authors conducted descriptive analyses to identify
      directors' overall opinions about service delivery practices and used
      multivariate analysis of variance to examine whether directors' opinions about
      service delivery practices differed according to agency characteristics. Findings
      showed differences in directors' opinions about service delivery practices based
      on their agency's service location. Practice recommendations were garnered from
      the study's results.

PMID- 23008055
TI  - Imaging obese patients: problems and solutions.
AB  - Obesity is an epidemic in the United States and Western World with an associated
      increasing impact on radiology departments. The increased prevalence of obesity
      in conjunction with the growing use and success of bariatric surgery results in
      an influx of obese patients into the health system in need of hospital services
      and care. Imaging services in particular are in demand in this patient
      population. Obese patients place special needs upon facilities and imaging
      equipment and also create technical challenges. This manuscript will address
      problems and potential solutions for imaging obese patients, specifically with
      regards to the modalities of radiography, fluoroscopy, computed tomography, and
      magnetic resonance imaging. 

PMID- 23008056
TI  - From action to interaction: exploring the contribution of body motion cues to
      social understanding in typical development and in autism spectrum disorders.
AB  - Two studies investigated whether typically developing children (TD) and children
      with autism spectrum disorders (ASD) were able to decide whether two characters
      were communicating or not on the basis of point-light displays. Point-lights
      portrayed actors engaged or not in a social interaction. In study 1, TD children
      (4-10 years old; n = 36) grasped social intentions from body language, with a
      notable improvement around 7/8. In study 2, children with ASD (6-12 years old; n
      = 12) could categorize the point-light displays at above-chance levels, but
      performed less efficiently, especially for the social interaction displays, than
      TD children (matched to chronological and non-verbal mental age, 6-12 years old;
      n = 24). An action representation deficit is discussed in relation to a social
      representation deficit and it is suggested that these deficits might be linked to
      altered maturational process of the mirror system in ASD.

PMID- 23008057
TI  - Autism training in pediatric residency: evaluation of a case-based curriculum.
AB  - Despite recent studies indicating the high prevalence of autism spectrum
      disorders (ASDs), there has been little focus on improving ASD education during
      pediatric residency training. The objective of this study was to evaluate a new
      curriculum developed in partnership with the Centers for Disease Control and
      Prevention and the Maternal and Child Health Bureau about ASDs. "Autism Case
      Training (ACT): A Developmental-Behavioral Pediatrics Curriculum" consists of 7
      case-based teaching modules. Modules were facilitated by faculty at 26 pediatric
      residency programs and data were obtained on 114 residents. Pre- and post-test
      data revealed significant short-term improvements in residents' knowledge and
      self-assessed competence regarding ASDs. Findings suggest that the ACT curriculum
      is effective in enhancing training about ASDs in pediatric residency programs.

PMID- 23008058
TI  - Excess mortality and causes of death in autism spectrum disorders: a follow up of
      the 1980s Utah/UCLA autism epidemiologic study.
AB  - This study's purpose was to investigate mortality among individuals with autism
      spectrum disorders (ASD) ascertained during a 1980s statewide autism prevalence
      study (n = 305) in relation to controls. Twenty-nine of these individuals (9.5 %)
      died by the time of follow up, representing a hazard rate ratio of 9.9 (95 % CI
      5.7-17.2) in relation to population controls. Death certificates identified
      respiratory, cardiac, and epileptic events as the most common causes of death.
      The elevated mortality risk associated with ASD in the study cohort appeared
      related to the presence of comorbid medical conditions and intellectual
      disability rather than ASD itself suggesting the importance of coordinated
      medical care for this high risk sub-population of individuals with ASD.

PMID- 23008059
TI  - Social anxiety predicts aggression in children with ASD: clinical comparisons
      with socially anxious and oppositional youth.
AB  - The present study examined the degree to which social anxiety predicts aggression
      in children with high functioning autism spectrum disorders (HFASD, n = 20)
      compared to children with Social Anxiety Disorder (SAD, n = 20) or with
      Oppositional Defiant Disorder or Conduct Disorder (ODD/CD, n = 20). As predicted,
      children with HFASD reported levels of humiliation/rejection fears commensurate
      with children with SAD and exhibited aggression at levels commensurate with
      ODD/CD, and a curvilinear relationship between social fears and aggression was
      found in the HFASD group only. Results indicate the possibility of an optimal
      level of social-evaluative fears that is unique for children with HFASD; too
      little social fear or too much may contribute to problems with aggression.

PMID- 23008060
TI  - HIF-1alpha and NOTCH signaling in ductal and lobular carcinomas of the breast.
AB  - BACKGROUND: NOTCH signaling is involved in every step of metazoan development and
      maintenance of adult tissue homeostasis. It is frequently deregulated by
      mutations and overexpression in different cancer types including solid tumors
      such as breast cancer. Another common feature of solid tumors is hypoxia, which
      occurs due to defective or insufficient vascularization. Hypoxia-inducible
      factors (HIFs) are key regulators of the homeostatic response to low oxygen
      levels. HIF-1alpha is overexpressed in many solid tumors, including breast
      cancer. Hypoxia-induced stabilization of HIF transcription factors has been shown
      to lead to NOTCH activation in vitro in different contexts and tissues, causing
      differentiation arrest and induction of proliferation and migration. METHODS:
      Since the link between HIF-1alpha and NOTCH signalling has hardly been studied,
      we set out to closely investigate associations between the expression of HIF
      1alpha and NOTCH pathway members in primary and metastatic human breast cancer
      specimens and their prognostic value. RESULTS: Co-expression of NOTCH1
      intracellular domain (N1ICD) and HIF-1alpha was associated with a high grade and
      a high proliferation rate in invasive breast cancer. HIF-1alpha expression was
      low in classic, but high in pleomorphic lobular cancers, which also frequently
      showed stromal HIF-1alpha expression. NOTCH1 pathway activation was
      prognostically unfavorable. CONCLUSION: In breast cancer, NOTCH pathway
      activation appears to be associated with a poor prognosis, but NOTCH and HIF
      signaling do not seem to be functionally associated.

PMID- 23008061
TI  - Differential response rates to irradiation among patients with human
      papillomavirus positive and negative oropharyngeal cancer.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the responsiveness of human papillomavirus
      (HPV) -positive and HPV-negative oropharyngeal cancer to intensity-modulated
      radiotherapy (IMRT), using axial imaging obtained daily during the course of
      image-guided radiotherapy (IGRT). STUDY DESIGN: Observational cohort study with
      matched-pair analysis of patients irradiated for HPV-positive and HPV-negative
      oropharygeal cancer. METHODS AND MATERIALS: Ten patients treated by IMRT to 70 Gy
      for locally advanced, HPV-positive squamous cell carcinoma of the oropharynx were
      matched to one HPV-negative control subject by age, gender, performance status, T
      category, tumor location, and the use of concurrent chemotherapy. The gross tumor
      volume (GTV) was delineated on daily IGRT scans obtained via kilovoltage cone
      beam computed tomography (CBCT). Mathematical modeling using fitted mixed-effects
      repeated measure analysis was performed to quantitatively and descriptively
      assess the trajectory of tumor regression. RESULTS: Patients with HPV-positive
      tumors experienced a more rapid rate of tumor regression between day 1 of IMRT
      and the beginning of week 2 (-33% Delta GTV) compared to their counterparts with
      HPV-negative tumors (-10% Delta GTV), which was statistically significant
      (p<0.001). During this initial period, the average absolute change in GTV was 
      22.9 cc/week for HPV-positive tumors and -5.9 cc/week for HPV-negative tumors
      (p<0.001). After week 2 of IMRT, the rates of GTV regression were comparable
      between the two groups. CONCLUSIONS: HPV-positive oropharyngeal cancers exhibited
      an enhanced response to radiation, characterized by a dramatically more rapid
      initial regression than those with HPV-negative tumors. Implications for
      treatment de-intensification in the context of future clinical trials and the
      possible mechanisms underlying this increased radiosensitivity will be discussed.

PMID- 23008062
TI  - Serial measurements of accommodation by open-field Hartmann-Shack wavefront
      aberrometer in eyes with accommodative spasm.
AB  - PURPOSE: To investigate the serial changes of accommodation and spherical
      aberration in eyes with accommodative spasm. METHODS: Four patients with
      accommodative spasm and ten healthy subjects were studied. The ocular refractive
      power (spherical equivalent) and spherical aberration were measured serially with
      an open-field, binocular Hartmann-Shack wavefront aberrometer. Patients and
      subjects wore full-correction lenses and were instructed to fixate a target set
      at 50 cm from the eye. The time-average of the refractive power, spherical
      aberration, and fluctuations of accommodation analyzed by the fast Fourier
      transform (FFT) of the two groups were compared. RESULTS: The average +/-
      standard deviation refractive power in the patients was significantly more
      negative than that in the healthy subject (-3.12 +/- 1.06 vs. -1.49 +/- 0.17 D).
      The integrated intensity of the FFT from 1 to 4 Hz was significantly higher in
      the patients than in the healthy subjects. The spherical aberration in patients
      was more negative than that in the healthy subjects (-0.033 +/- 0.048 MUm vs.
      0.002 +/- 0.027 MUm). CONCLUSIONS: Eyes with accommodative spasm are
      characterized by a lead of accommodation with greater fluctuations and negative
      spherical aberrations. Excessive accommodation can be measured objectively in
      such eyes with a binocular wavefront aberrometer without cycloplegics.

PMID- 23008063
TI  - Preparation of pixantrone/poly(gamma-glutamic acid) nanoparticles through complex
      self-assembly for oral chemotherapy.
AB  - A facile and green approach is reported to construct pixantrone/poly(gamma
      glutamic acid) nanoparticles (PIX/gamma-PGA NPs) as an oral drug delivery system
      through the complex self-assembly of polyelectrolyte gamma-PGA and the anticancer
      drug pixantrone dimaleate (PDM). The complex self-assembly behavior is
      investigated in detail. The results demonstrate that PDM can interact with gamma
      PGA to conveniently form NPs and the size of NPs can be controlled by adjusting
      the solution volume ratio of PDM to gamma-PGA. These NPs illustrate their pH
      dependent release behavior, efficient cellular uptake and enhanced drug efficacy
      through an in vitro release study, flow cytometry, CLSM analysis and the MTT
      assay. In summary, PIX/gamma-PGA NPs may serve as a promising oral drug delivery
      system for cancer therapy.

PMID- 23008065
TI  - Electrospray ionization and collision-induced dissociation tandem mass
      spectrometric discrimination of polyphenolic glycosides: exact acylation site
      determination of the O-acylated monosaccharide residues.
AB  - RATIONALE: Acylated monosaccharide residues are structural subunits of natural
      products or synthetic intermediates that have received much attention in past
      years. Determination of the acylation sites of these residues still relies
      heavily on the comparison of their characteristic NMR signals with those of known
      standards and synthesized acylated glycosides. It is important to develop a rapid
      analytical method for determining the acylation sites for these compounds, and
      this is described in this study. METHODS: Six known polyphenolic glycosides were
      used for the electrospray ionization and collision-induced dissociation tandem
      mass spectrometry (ESI-CID-MS/MS) discrimination of the acylated monosaccharide
      residues with different acylation sites. A combination of ESI-CID-MS/MS, using a
      triple quadrupole mass spectrometer, with ultra-performance liquid chromatography
      (UPLC) and photo-diode array (PDA) detection (UPLC-PDA) has been applied to the
      identification or characterization of polyphenolic glycosides in Polygonum
      capitatum that possess an acylated monosaccharide residue. RESULTS: An ESI-MS and
      CID-MS/MS method has been developed for the determination of the acylation sites
      of polyphenolic glycosides that possess an acylated monosaccharide residue.
      Twelve polyphenolic glycosides including four new ones have been identified or
      characterized in P. capitatum. Eight (including the new ones) of the twelve
      glycosides were reported for the first time from this plant. CONCLUSIONS: The
      developed ESI-MS and CID-MS/MS method provided a very useful strategy for the
      determination of the sites of polyphenolic glycosides that possess an acylated
      monosaccharide residue. The acylation site could be determined by the
      characteristic product ion spectra of the in-source CID-generated O-acyl
      monosaccharide ion [B(1)](+). The presented work may facilitate the structural
      characterization of these types of compounds.

PMID- 23008066
TI  - Stable-isotope labeling and probing of recent photosynthates into respired CO2,
      soil microbes and soil mesofauna using a xylem and phloem stem-injection
      technique on Sitka spruce (Picea sitchensis).
AB  - RATIONALE: Here we report on the successful application of a novel stem-injection
      stable-isotope-labeling and probing technique in mature trees to trace the
      spatial and temporal distribution of rhizosphere carbon belowground. METHODS:
      Three 22-year-old Sitka spruce trees were injected with 6.66 g of (13)C-labeled
      aspartic acid. Over the succeeding 30 days, soil CO(2) efflux, phospholipid fatty
      acid (PLFA) microbial biomarkers and soil invertebrates (mites, collembolans and
      enchytraeids) were analyzed along a 50 m transect from each tree to determine the
      temporal and spatial patterns in the translocation of recently fixed
      photosynthates belowground. RESULTS: Soil delta(13)CO(2) values peaked 13-23 days
      after injection, up to 5 m from the base of the injected tree and was, on
      average, 3.50/00 enriched in (13)C relative to the baseline. Fungal PLFA
      biomarkers peaked 2-4 days after stem-injection, up to 20 m from the base of the
      injected tree and were (13)C-enriched by up to 500/00. Significant (13)C
      enrichment in mites and enchytraeids occurred 4-6 days after injection (by, on
      average, 1.50/00). CONCLUSIONS: Stem injection of large trees with (13)C-enriched
      compounds is a successful tool to trace C-translocation belowground. In
      particular, the significant (13)C enrichment of CO(2) and enchytraeids near the
      base of the tree and the significant (13)C enrichment of PLFAs up to 20 m away
      indicate that mature Sitka spruce (Picea sitchensis) have the capacity to support
      soil communities over large distances.

PMID- 23008064
TI  - Growth control in colon epithelial cells: gadolinium enhances calcium-mediated
      growth regulation.
AB  - Gadolinium, a member of the lanthanoid family of transition metals, interacts
      with calcium-binding sites on proteins and other biological molecules. The
      overall goal of the present investigation was to determine if gadolinium could
      enhance calcium-induced epithelial cell growth inhibition in the colon.
      Gadolinium at concentrations as low as 1-5 MUM combined with calcium inhibits
      proliferation of human colonic epithelial cells more effectively than calcium
      alone. Gadolinium had no detectable effect on calcium-induced differentiation in
      the same cells based on change in cell morphology, induction of E-cadherin
      synthesis, and translocation of E-cadherin from the cytosol to the cell surface.
      When the colon epithelial cells were treated with gadolinium and then exposed to
      increased calcium concentrations, movement of extracellular calcium into the cell
      was suppressed. In contrast, gadolinium treatment had no effect on ionomycin
      induced release of stored intracellular calcium into the cytoplasm. Whether these
      in vitro observations can be translated into an approach for reducing abnormal
      proliferation in the colonic mucosa (including polyp formation) is not known.
      These results do, however, provide an explanation for our recent findings that a
      multi-mineral supplement containing all of the naturally occurring lanthanoid
      metals including gadolinium are more effective than calcium alone in preventing
      colon polyp formation in mice on a high-fat diet.

PMID- 23008067
TI  - Tandem mass spectrometric analysis and density functional theory calculations on
      the fragmentation behavior of two tetradecanoylingenol regioisomers from
      Euphorbia wallichii.
AB  - RATIONALE: Two structurally similar bioactive regioisomers, 3-O
      tetradecanoylingenol and 20-O-tetradecanoylingenol, from Euphorbia wallichii
      presented quite different fragmentation behaviors. Revealing the related
      fragmentation pathways may improve the efficiency of characterization and
      identification of such type of compounds. METHODS: The two regioisomers were
      subjected to collision-induced dissociation (CID) on Finnigan LCQ(DECA) and LTQ
      Orbitrap XL instruments. Based on the CID results, the possible fragmentation
      pathways were proposed and investigated with density functional theory (DFT)
      calculations. RESULTS: Elimination of C(14)H(28)O(2) (tetradecanoic acid) for 3-O
      tetradecanoylingenol and the sequential losses of C(4)H(8) (butylene) for 20-O
      tetradecanoylingenol were observed in ESI-MS/MS, witnessed also by HR-ESI-MS/MS.
      The fragmentation pathways were proposed and verified by calculating the
      activation energy of their transition states by DFT calculations. CONCLUSIONS:
      Based on the observations, fragmentation pathways for the two regioisomers were
      proposed and verified by calculating the energy of the reactants, products and
      the corresponding transition states using DFT. This report should have value in
      rapid identification of the derivatives of ingenol and other regioisomers in
      natural products.

PMID- 23008068
TI  - An experimental and theoretical study on fragmentation of protonated N-(2
      pyridinylmethyl)indole in electrospray ionization mass spectrometry.
AB  - RATIONALE: The dissociation reactions of protonated molecules are the base of
      structural analysis in electrospray ionization tandem mass spectrometry (ESI
      MS(n)). However, general rules for elucidating the numerous fragmentation
      reactions in ESI-MS(n) are still rather lacking. Therefore, it is very important
      at all times to carry out mechanistic investigations for fragmentation reactions
      in the gas phase. METHODS: The fragmentation reactions of protonated N-(2
      pyridinylmethyl)indoles were studied by both of ESI ion trap tandem mass
      spectrometry and ESI Fourier transform ion cyclotron resonance tandem mass
      spectrometry in positive-ion mode. RESULTS: In ESI-MS/MS, the ionizing proton is
      first bound to the most thermodynamically favored site, the pyridine nitrogen;
      then it transfers to the dissociative protonation sites and triggers the
      fragmentation. In the fragmentation of the target compounds, some interesting
      reactions, such as rearrangement, proton transfer and electron transfer
      reactions, take place via ion/neutral complexes. The proposed mechanisms are
      supported by both theoretical calculations and isotopic labeling experiments.
      CONCLUSIONS: This study is a case for better understanding the dissociative
      protonation sites and enriching the knowledge about the role of ion/neutral
      complexes in ESI-MS. It also provides useful information for the structural
      analysis of organic compounds, especially drug analysis in pharmaceutical
      chemistry.

PMID- 23008069
TI  - Investigation of the ionization mechanism of polycyclic aromatic hydrocarbons
      using an ethanol/bromobenzene/chlorobenzene/anisole mixture as a dopant in liquid
      chromatography/atmospheric pressure photoionization mass spectrometry.
AB  - RATIONALE: An ethanol-based multicomponent dopant consisting of
      ethanol/chlorobenzene/bromobenzene/anisole (98.975:0.1:0.9:0.025, v/v/v/v) has
      been used as a dopant for atmospheric pressure photoionization (APPI) of
      polycyclic aromatic hydrocarbons (PAHs). In this study the mechanism of
      ionization of PAHs assisted by the ethanol-based multicomponent dopant is
      investigated. METHODS: The reactant background cluster ions of the ethanol-based
      multicomponent dopant observed in the positive ion APPI were studied. These
      studies were performed to investigate the mechanism behind the generation of a
      molecular radical cation (M(+*)) for PAHs by APPI assisted by the ethanol-based
      multicomponent dopant. Full scan and MS/MS analyses were conducted using an LTQ
      Orbitrap mass spectrometer. The effect of acidification of the mobile phase on
      the dopant cluster ion formation was also investigated. RESULTS: With the ethanol
      based multicomponent dopant, a single type of molecular radical cation M(+*) was
      observed for the studied PAHs. The characteristic ion signal of the
      multicomponent dopant mixture consisted of mainly anisole photoions at m/z
      108.05697 and its adduct ions at m/z 124.05188 and 164.07061. The anisole ion
      response at m/z 108.05697 was stable in the presence of acetonitrile, methanol,
      water and 0.1% formic acid mobile phase composition. CONCLUSIONS: The abundance
      formation of anisole photoions shows the universality of this multicomponent
      dopant in ionizing compounds with ionization energy ranging from 7.1-8.2 eV.
      Since the ionization energy of anisole is 8.2 eV and is lower than those of
      chlorobenzene (9.07 eV) and bromobenzene (9.0 eV), the mechanism of formation of
      anisole photoions even with its very minute amounts was not only governed by its
      photoionization by the krypton lamp photon energy (10.0 eV and 10.6 eV), but also
      by charge transfer from bromobenzene and chlorobenzene radical cations. PAH
      molecules were mainly ionized by charge transfer reaction from photoionized
      anisole and oxidized anisole radical cations as well as by the krypton lamp.

PMID- 23008070
TI  - Extension of the focusable mass range in distance-of-flight mass spectrometry
      with multiple detectors.
AB  - RATIONALE: Distance-of-flight mass spectrometry (DOFMS) is a velocity-based mass
      separation technique in which ions are spread across a spatially selective
      detector according to m/z. In this work, we investigate the practical mass range
      available for DOFMS with a finite-length detector. METHODS: A glow-discharge
      DOFMS instrument has been constructed for the analysis of atomic ions. This
      instrument was modified to accommodate two spatially selective ion detectors,
      arranged co-linearly, along the mass-separation axis of the analyzer. With this
      geometry, each detector covers a different portion of the distance-of-flight
      spectrum and ions are detected simultaneously at the two detectors. The total
      flight distance covered by the two detectors is 106 mm and simulates DOF
      detection across a broad mass range. RESULTS: DOFMS theory predicts that ions of
      all m/z values are focused at a single flight time, but at m/z-dependent flight
      distances. Therefore, ions that are detected across a wide portion of the DOF
      axis should all yield the same peak widths. With a focal-plane camera detector
      and a micro-channel plate/phosphor-screen detection assembly, we found
      simultaneous, uniform focus of (40)Ar(2)(+) and of (65)Cu(+) and (63)Cu(+) with
      the ions spread 82 mm across the DOF axis. This detection length, combined with
      the current instrument geometry, allows for a simultaneously detectable m/z value
      of 4:3 (high mass-to-low mass). CONCLUSIONS: These results are the first
      experimental verification that constant-momentum acceleration (CMA)-DOFMS
      provides energy focus across an extended detection length. Evidence presented
      demonstrates that DOFMS is amenable to detection with (at least) a 100-mm
      detector surface. These results indicate that DOFMS is well suited for detection
      of broader mass ranges.

PMID- 23008071
TI  - Anomalously long-lived molecular negative ions of duroquinone.
AB  - The problem under investigation here is establishment of mechanisms of the
      resonant electron capture by molecules, using the example of duroquinone (2,3,5,6
      tetramethyl-1,4-benzoquinone). A solution is important because it will provide
      new insights into the fundamental physical laws and widespread applications in
      various fields like molecular nanoelectronics, touched upon herein too. Resonant
      electron capture (REC) in duroquinone was studied with negative ion mass
      spectrometry of the REC as the main method, and UV absorption and the
      photoelectron spectroscopy as the auxiliary ones. The latter were used to study
      the electronic structures of the various neutral molecular states that are the
      parent ones for the negative molecular ions formed by electron attachment to the
      molecules. B3LYP/6-311 + G(d,p) calculations were widely used throughout the
      study. As a result, an intensive peak of the negative molecular ions with
      anomalously high lifetime (200 microseconds) was registered at the attached
      electron energy of 1.8 eV. The ions were determined to be quartets delaying the
      electron autodetachment because of spin prohibition and appearing via inter
      system crossing from the negative molecular ion doublets produced in the core
      excited Feshbach resonances. Finally, the pattern of the REC in duroquinone was
      obtained for the energy region of 1-4 eV which is presented by shape resonances,
      core-excited Feshbach resonances and by mechanisms little-known for molecules of
      inter-shell resonances and the formation of ion quartets. The latter were
      proposed to be related to the negative differential resistance in molecular
      nanoelectronics.

PMID- 23008072
TI  - Extraction and analysis of carnitine and acylcarnitines by electrospray
      ionization tandem mass spectrometry directly from dried blood and plasma spots
      using a novel autosampler.
AB  - RATIONALE: Acylcarnitines are routinely analyzed by electrospray ionization
      tandem mass spectrometry (ESI-MS/MS) both in clinical diagnostic and public
      health newborn screening laboratories from plasma and dried whole blood spots
      (DBS) on filter paper. The use of DBS as a convenient method of collecting and
      storing samples for subsequent analysis of various biomolecules is increasing,
      thus prompting the development of new devices to recover and quantify such
      analytes in an automated manner. METHODS: Acylcarnitines were extracted directly
      from DBS using a novel autosampler that sequentially loads DBS cards into a
      pneumatic clamp and then pumps a fixed volume of solvent containing appropriate
      internal standards through a section of the DBS card directly into a triple
      quadrupole mass spectrometer via ESI. Plasma was first spiked with internal
      standard then spotted onto filter paper for analysis. RESULTS: Acylcarnitines
      were analyzed in DBS, and both free and total carnitine were assayed in dried
      plasma spots (DPS). Results using the new autosampling technique were of equal
      quality to those obtained by punching a 3-mm diameter disk from a DBS or DPS,
      then extracting and analyzing the target analytes from conventional 96-well
      microtiter plates, with far reduced time per sample. Recovery for most analytes
      was >60% and reproducibility was generally within 20% (CV). CONCLUSIONS: The
      simplicity and robustness of the DBS autosampler make it an attractive
      alternative to conventional methods of analyzing DBS specimens, thus saving time
      and labor costs, especially in high-throughput applications. Although the method
      as described is for direct infusion analysis, the autosampler is easily coupled
      to column hardware for applications requiring liquid chromatography/mass
      spectrometry (LC/MS).

PMID- 23008073
TI  - Analysis of the differentially expressed low molecular weight peptides in human
      serum via an N-terminal isotope labeling technique combining nano-liquid
      chromatography/matrix-assisted laser desorption/ionization mass spectrometry.
AB  - RATIONALE: Peptidomics analysis of human serum is challenging due to the low
      abundance of serum peptides and interference from the complex matrix. This study
      analyzed the differentially expressed (DE) low molecular weight peptides in human
      serum integrating a DMPITC-based N-terminal isotope labeling technique with nano
      liquid chromatography and matrix-assisted laser desorption/ionization mass
      spectrometry (nano-LC/MALDI-MS). METHODS: The workflow introduced a [d(6)]-4,6
      dimethoxypyrimidine-2-isothiocyanate (DMPITC)-labeled mixture of aliquots from
      test samples as the internal standard. The spiked [d(0)]-DMPITC-labeled samples
      were separated by nano-LC then spotted on the MALDI target. Both quantitative and
      qualitative studies for serum peptides were achieved based on the isotope-labeled
      peaks. RESULTS: The DMPITC labeling technique combined with nano-LC/MALDI-MS not
      only minimized the errors in peptide quantitation, but also allowed convenient
      recognition of the labeled peptides due to the 6 Da mass difference. The data
      showed that the entire research procedure as well as the subsequent data analysis
      method were effective, reproducible, and sensitive for the analysis of DE serum
      peptides. CONCLUSIONS: This study successfully established a research model for
      DE serum peptides using DMPITC-based N-terminal isotope labeling and nano
      LC/MALDI-MS. Application of the DMPITC-based N-terminal labeling technique is
      expected to provide a promising tool for the investigation of peptides in vivo,
      especially for the analysis of DE peptides under different biological conditions.

PMID- 23008074
TI  - Detection of Cu(III)-containing [Diclofenac-H+CuNO3]+ ion by electrospray
      ionization mass spectrometry.

PMID- 23008075
TI  - Expression of chemokine CCL20 in ulcerative colitis.
AB  - The aim of the current study was to investigate the expression of chemokine CCL20
      in ulcerative colitis (UC) patients and in dextran sulfate sodium (DSS)-induced
      experimental colitis in mice. The expression of the CCL20 protein in colonic
      mucosa was detected in 65 UC patients and in 30 normal patients. A total of 40
      female BALB/c mice were divided into a control and model group; the latter was
      fed a 5% DSS solution ad libitum for 7 days to induce experimental colitis. The
      disease activity index (DAI) and histological score were assessed and the
      expression of CCL20 mRNA and protein was determined. CCL20 was expressed in the
      UC group. It was either weakly expressed or not expressed in the normal control
      group. Additionally, the expression of CCL20 in the UC group was significantly
      higher compared with that in the control groups (P<0.01). The expression levels
      of CCL20 mRNA and protein were significantly increased in the model group
      compared with those in the control group (P<0.01) and positively correlated with
      the severity of colonic inflammation. The results from the present study
      demonsrtate that CCL20 positively correlates with UC. CCL20 may play a
      significant role in local damage and pathological changes in UC and may serve as
      a potential target for therapy.

PMID- 23008076
TI  - Twenty predictions for the future of CPD: implications of the shift from the
      update model to improving clinical practice.

PMID- 23008077
TI  - A randomized trial assessing the impact of a personal printed feedback portrait
      on statin prescribing in primary care.
AB  - INTRODUCTION: Knowledge translation (KT) initiatives have the potential to
      improve prescribing quality and produce savings that exceed the cost of the KT
      program itself, including the cost of evaluation using pragmatic study methods.
      Our objective was to measure the impact and estimated savings resulting from the
      distribution of individualized physician portraits of statin prescribing along
      with therapeutic recommendations in British Columbia, Canada. METHODS: A paired
      community design was used to study 2 725 family physicians in British Columbia.
      Communities were paired according to number of physicians and geographic
      location, with one community of each pair randomly assigned to an early (n = 1
      349) or delayed (n = 1 376) intervention group. The intervention was a
      personalized prescribing portrait on statins that included therapeutic
      recommendations. The primary outcome was the impact on new prescribing (defined
      as statin naive) for primary prevention (defined as no diagnosis of
      cardiovascular disease) as recorded in the administrative claims databases of the
      BC Ministry of Health. RESULTS: Compared to the delayed control group, the
      relative probability of a new statin prescription for primary prevention
      decreased by 6% in the 12 months after the Education for Quality Improvement in
      Patient Care (EQIP) portrait compared to the preceding 12 months (relative risk
      [RR] 0.94; 95% confidence interval [CI] 0.91-0.98). There was also a non
      statistically significant decrease in new prescribing for secondary prevention in
      patients diagnosed with cardiovascular disease (RR 0.96; 95% CI 0.91-1.01). We
      estimated that 572 fewer patients started statins for primary prevention in the
      first year after the portrait was mailed compared to patients in the delayed
      practices. We estimated the statin cost for those patients as $465,000 in the
      first two years, while the KT program to provide statin portraits cost less than
      $100,000. DISCUSSION: The individualized prescribing portrait had a significant
      beneficial effect on new statin prescribing for primary prevention but not
      secondary prevention. Provincial drug plan costs appear to have been reduced to a
      level that exceeded the cost of the program.

PMID- 23008078
TI  - Efficacy of continuing education in improving pharmacists' competencies for
      providing weight management service: three-arm randomized controlled trial.
AB  - INTRODUCTION: Weight management is a new public health role for community
      pharmacists in many countries. Lack of expertise is one of the key barriers to
      counseling obese patients. We evaluated the comparative efficacy of three
      alternative continuing education (CE) meetings on weight management. METHODS: We
      designed a randomized controlled trial comparing didactic lecture, lecture plus
      case discussion, and lecture plus small-group training. It was conducted in 2011
      in Tehran. Pharmacists' knowledge, attitudes, and competence were evaluated
      immediately before, immediately after and one month after each meeting via
      standardized questionnaires and case vignettes. Participants' satisfaction was
      evaluated after each meeting. Data were analyzed using repeated measure analysis
      of variance and chi-squared tests. RESULTS: Sixty pharmacists were randomly
      allocated to each study arm. There were no demographic differences between the
      arms at the baseline. The knowledge scores significantly improved for all
      interventions over time. At the follow-up, the small-group training arm obtained
      significantly higher knowledge scores (p < 0.001, effect size = 0.54). The
      competence scores in lecture plus case discussion and lecture plus small-group
      training meetings improved over time (effect size 0.14 and 0.34; difference
      nonsignificant). Small-group training resulted in significantly higher
      satisfaction scores (p = 0.005). The interventions' effects on attitudes were
      similar. DISCUSSION: This is the first study on the implementation and efficacy
      of various types of CE meetings for community pharmacists to provide weight
      management services. Lecture plus small group training resulted in better
      learning retention over time and higher satisfaction. Future studies should
      evaluate the effects of various types of CE meetings on pharmacists' behavior and
      their cost-effectiveness.

PMID- 23008079
TI  - Development of a competency framework for quality improvement in family medicine:
      a qualitative study.
AB  - OBJECTIVE: The aim of this study was to develop a comprehensive framework of
      quality improvement competencies for use in continuing professional development
      (CPD) and continuing medical education (CME) for European general practice/family
      medicine physicians (GPs/FDs). METHODS: The study was carried out in three
      phases: literature review, consensus development panels, and Delphi technique. An
      initial competencies framework was developed from an extensive literature review
      focusing on literature in English from 2000 to 2011 and addressing quality
      improvement competencies for general practitioners in continuous education
      programs. Two rounds of reviews by consensus development panels were undertaken
      to evaluate and make changes to the initial draft competency framework. Then two
      rounds of Delphi surveys were carried out in an effort to reach consensus on the
      domains and competencies included in the framework. Our goal was for 90% to 100%
      consensus. Both surveys were presented through SurveyMonkey, an online survey
      service, and sent by e-mail to members of the European Association for Quality
      and Patient Safety in General Practice/Family Medicine (EQuiP), a network
      organization of Wonca Europe. RESULTS: The Quality Improvement Competencies
      Framework was developed. It consists of a list of 35 competencies organized into
      the following domains: Patient Care & Safety, Effectiveness & Efficiency, Equity
      & Ethical Practice, Methods & Tools, Leadership & Management, and Continuing
      Professional Education. CONCLUSION: We believe that the framework can serve as a
      useful tool for identifying gaps in knowledge and skills and guiding the
      development of CPD and CME curricula for GPs/FDs not only in Europe but also in
      other regions, including the United States and Canada, on the assumption that
      many of the core tasks of quality improvement would be relevant across multiple
      contexts.

PMID- 23008080
TI  - Using the cascade model to improve antenatal screening for the hemoglobin
      disorders.
AB  - INTRODUCTION: The inherited hemoglobin disorders constitute a major public health
      problem. Facilitators (experienced hemoglobin counselors) were trained to deliver
      knowledge and skills to "frontline" practitioners to enable them to support
      parents during antenatal screening via a cascade (train-the-trainer) model.
      Objectives of evaluation were to explore the extent that the cascade model was
      perceived to be embedded in practice, identify enablers and barriers to effective
      cascading, assess the feasibility of incorporating e-learning into the model, and
      obtain the facilitators' perceptions of the change process. METHODS: Focus groups
      and interviews were undertaken with 50 facilitators. Data were analyzed
      thematically. RESULTS: Cascading was influenced by contextual factors operating
      in the work environment, especially workload, existing roles and responsibilities
      and adequate preparation. Facilitators' confidence and perceptions of success
      varied for individuals in the same workplace exposed to the same opportunities to
      receive and deliver training. Cascading could by enhanced by carefully selecting
      potential facilitators, training needs assessment to identify the knowledge and
      skills required by individuals, and follow-up to offer ongoing support.
      DISCUSSION: Evaluation demonstrated the importance of contextual and individual
      factors to successful cascading and the feasibility of combining it with e
      learning. Future evaluations should consider the perspectives of all
      stakeholders, namely managers, recipients of cascading and clients, and cost
      effectiveness.

PMID- 23008081
TI  - Refer2Quit: impact of Web-based skills training on tobacco interventions and
      quitline referrals.
AB  - INTRODUCTION: Tobacco quitlines (QLs) provide effective evidence-based tobacco
      cessation counseling, yet they remain underutilized. Barriers to utilization
      include the lack of referrals by health care providers who typically have little
      knowledge about QLs and low self-efficacy for providing tobacco interventions. In
      order to educate providers about QLs, referral methods and tobacco interventions,
      a case-based online CME/CE program, Refer2Quit (R2Q), was developed. R2Q includes
      QL education and intervention and referral skills training tailored to provider
      type (eg, physician, nurse, dental provider, pharmacist) and work setting (eg,
      emergency, outpatient, inpatient). A module teaching motivational enhancement
      strategies was also included. METHODS: Four health care organizations in
      Washington State participated in a study examining the effects of R2Q training on
      fax referral rates in an interrupted times series. Attitudes and self-efficacy
      toward delivering tobacco interventions was also assessed. Participants were a
      mix of provider types, including prescribers (20.1%), RNs (46.7%), and others
      (33.2%). RESULTS: Health care sites that participated in the study increased the
      fax referral rates (odds ratio [OR] 2.86, confidence interval [CI] 1.52-6.00) as
      well as rates of referrals that converted to actual quitline registrations (OR
      2.73, CI 1.0-7.4). Providers who completed the training expressed significantly
      more positive attitudes and improved self-efficacy for delivering tobacco
      services. At follow-up most providers reported increased delivery of tobacco
      interventions and QL referrals, although only 17% reported increased rates of fax
      referral. DISCUSSION: Our study suggests that online education builds skills,
      improves knowledge, and thus increases the number and quality of fax referrals
      made to QLs by health care providers. Providers nonetheless reported ongoing
      barriers to providing tobacco services and referral, including lack of
      reimbursement and patient unwillingness to accept a referral.

PMID- 23008082
TI  - Impact of interprofessional education on collaboration attitudes, skills, and
      behavior among primary care professionals.
AB  - INTRODUCTION: Care for the frail elderly is often provided by several
      professionals. Collaboration between them is essential, but remains difficult to
      achieve. Interprofessional education (IPE) can improve this collaboration. We
      developed a 9-hour IPE program for primary care professionals from 7 disciplines
      caring for the frail elderly, and aimed to establish whether the program improved
      professionals' interprofessional attitudes and attitudes toward collaboration,
      collaboration skills, and collaborative behavior. We also evaluated learners'
      reactions to the program. METHODS: Before-after study, using the
      Interprofessional Attitudes Questionnaire (IAQ, score:1 to 7); Attitudes Toward
      Health Care Teams Scale (ATHCTS, score: 0 to 105); and Team Skills Scale (TSS,
      score:17 to 85). Additionally, semistructured interviews were conducted with 10
      selected participants. RESULTS: Participants' (N = 80) overall interprofessional
      attitudes improved (IAQ baseline: 5.49; follow-up: 5.67, p = 0.001); attitudes
      toward geriatric teams did not change (ATHCTS baseline: 69.9; follow-up: 69.1, p
      = 0.32). Participants' self-reported team skills improved (TSS baseline: 45.7;
      follow-up: 48.1, p = 0.001). In the interviews, many interviewees reported
      increased collaboration with professionals of other disciplines due to the
      program. Interviewees considered the program's interprofessional nature and
      attending the program with local professionals important contributing factors to
      the experienced improvements in collaboration. However, they also noted that not
      all parts of the program had met the needs of all participating disciplines, due
      to differences in professional background and knowledge. DISCUSSION: A brief IPE
      program can improve interprofessional attitudes, collaboration skills, and
      collaborative behavior. That such a program allows professionals to get
      acquainted with each other and each other's viewpoints appears to be as important
      as the educational content.

PMID- 23008083
TI  - Attendees' perceptions of commercial influence in noncommercially funded CME
      programs.
AB  - INTRODUCTION: The controversy surrounding commercial support for continuing
      medical education (CME) programs has led to policy changes, but data show no
      significant difference in perceived bias between commercial and noncommercial
      CME. Indeed, what attendees perceive as commercial influence is not fully
      understood. We sought to clarify what sources contribute to attendees'
      perceptions of commercial influence in non-industry-supported CME programs, and
      how attendees perceive that this influence manifests itself on both speaker and
      program levels. METHODS: Evaluation forms were received from 1 544 attendees at
      14 live noncommercially supported CME programs in 2006, 2007, and 2010. Attendees
      rated perceived commercial influence for each lecture and the entire program.
      Using open-ended and "check all that apply'' questions, participants specified
      perceived sources and manifestations of commercial influence. RESULTS: Attendees
      rating individual lectures but not the entire program as commercially influenced
      accounted for 59.9% of those who identified bias. The most frequently endorsed
      source of commercial influence was individual speakers' funding, and the most
      listed manifestations were speakers' mentions of pharmaceuticals and expressions
      of personal opinions. Rating the entire program commercially influenced
      correlated with whether attendees considered the funding of referenced research a
      source of influence. DISCUSSION: CME attendees consider a broad spectrum of
      factors when reporting commercial influence. Evaluation forms should include bias
      questions per lecture as well as items to clarify perceived sources and
      manifestations of commercial influence.

PMID- 23008084
TI  - Continuing education that matters: a successful, evidence-based course with
      minimal pharmaceutical funding.

PMID- 23008085
TI  - [Isolated noncompaction cardiomyopathy with special emphasis on arrhythmia
      complications].
AB  - Isolated noncompaction cardiomyopathy (NCCM) is a rare genetically determined
      myocardial disease caused by abnormal fetal development of the myocardium
      resulting in a thin compacted and a thicker noncompacted layer of the affected
      left ventricular (LV) wall. The genetic basis of NCCM is heterogenous. Diagnosis
      can be made using echocardiography or magnetic resonance imaging. The diagnostic
      criteria for NCCM are still under discussion. Afflicted patients may present with
      various symptoms caused by arrhythmias, heart failure and cardioembolic events.
      Severely reduced LV function as well as left bundle branch block and atrial
      fibrillation were shown to be linked to worse outcomes. Treatment in patients
      with NCCM should be targeted at individual symptoms and clinical findings.
      Therapy includes pharmacological treatment, and in individual cases ablation or
      device therapy, as well as consideration for heart transplantation in selected
      cases. Aside from regular clinical follow-up of patients with NCCM screening of
      first degree family members with assessment of medical history, physical
      examination, ECG recording, and echocardiography are recommended.

PMID- 23008087
TI  - Foamy gland pancreatic ductal adenocarcinoma diagnosed on EUS-FNA: a
      histochemical, immunohistochemical, and molecular report.
AB  - The foamy gland pattern (FGP) may impart to pancreatic ductal adenocarcinoma
      (PDA) a deceptively benign appearance. Thus, its diagnosis on FNA is challenging.
      A case of PDA with FGP, that was suspected on Diff Quik smears, diagnosed on cell
      block preparation and confirmed by ancillary stains and molecular techniques, is
      here reported. The diagnostic interpretation of foamy atypical cells on direct
      smears may benefit from cell block preparation and from ancillary techniques.

PMID- 23008086
TI  - Insights and challenges in hypertrophic cardiomyopathy, 2012.
AB  - We present a contemporary overview of hypertrophic cardiomyopathy (HCM),
      incorporating recent thinking on disease mechanisms and advances in therapy.
      Clinical, pathological, genetic, and mechanistic definitions of HCM are
      discussed. The genetic profile of HCM in both adults and children is explored to
      the extent of present knowledge. The spectrum of morphological and histological
      abnormalities in HCM is reviewed, including involvement of the right ventricle,
      which is less widely recognised. Morbidity and mortality from HCM may result from
      diastolic dysfunction, ischaemia, left ventricular outflow tract obstruction,
      mitral regurgitation, supraventricular and ventricular arrhythmia, or--less
      commonly--progression to "burnt out" disease or sudden cardiac death (SCD).
      Defibrillators offer an efficacious means of averting SCD, but are not without
      their complications, underscoring the importance of identifying at-risk cases. We
      address the strengths and weaknesses of prognostication based on readily
      obtainable clinical markers, and discuss the integration of auxiliary approaches
      such as genotyping, cardiovascular magnetic resonance, and fractionation analysis
      into existing risk stratification guidelines. Finally, we provide an update on
      the pharmacological and interventional management of HCM, including the advent of
      disease-modifying therapy.

PMID- 23008090
TI  - Self-monitoring of blood glucose (SMBG) improves glycaemic control in oral
      hypoglycaemic agent (OHA)-treated type 2 diabetes (SMBG-OHA study).
AB  - BACKGROUND: We conducted a clinical research study to determine the effect of
      self-monitoring of blood glucose (SMBG) on glycaemic control and the value of a
      putatively less painful blood sampling technique on SMBG in oral hypoglycaemic
      agent-treated type 2 diabetes patients; SMBG has not been broadly applied in non
      insulin-treated patients in Japan. METHODS: One hundred thirty-seven subjects
      were recruited for the 24-week, prospective, comparison study and randomized into
      three groups: 46, no SMBG group; 46, fingertip group; and 45, palm group. The
      primary endpoint was change in HbA(1c). The secondary endpoints were SMBG
      compliance, dropout rate, treatment changes, and patient's and physician's
      satisfaction. RESULTS: Six subjects in the fingertip group (13.2%) and one
      subject in the palm group (2.2%) were dropped because of pain. A(1C) level of all
      subjects at 24-week was decreased more in the fingertip (-0.23%) and palm (
      0.16%) groups than that in the no SMBG group (+0.31%) (p < 0.05). SMBG compliance
      was higher in the fingertip group (2.17 times/day) than that in the palm group
      (1.65 times/day) (p < 0.05). A(1C) level of treatment-unchanged subjects was
      decreased more in the fingertip (-0.25%) and palm (-0.21%) groups than that in
      the no SMBG group (+0.30%) (p < 0.05). SMBG compliance was higher in the
      fingertip group (2.24 times/day) than that in the palm group (1.65 times/day) (p
      < 0.05). Patient's questionnaire showed that 84.1% of the fingertip group and
      90.2% of the palm group were satisfied with SMBG. Physician's satisfaction was
      higher in the palm group (94.0%) than that in the fingertip group (80.0%) (p <
      0.05). CONCLUSION: SMBG is beneficial for glycaemic control, and palm blood
      sampling is a useful procedure for oral hypoglycaemic agent-treated type 2
      diabetes.

PMID- 23008091
TI  - Morbidity and mortality following transarterial liver chemoembolization in
      patients with hepatocellular carcinoma and synthetic hepatic dysfunction.
AB  - The purpose of this study was to determine the rate and risk factors for the
      development of irreversible hepatotoxicity after transarterial chemoembolization
      (TACE) in patients with hepatocellular carcinoma (HCC) and synthetic hepatic
      dysfunction. Two hundred fifty-one consecutive patients with HCC and hepatic
      dysfunction who underwent 443 TACE procedures from 2005 to 2010 were
      retrospectively reviewed. The included patients met one of the following
      criteria: a pre-TACE bilirubin level >= 2 mg/dL, an international normalized
      ratio (INR) > 1.5, a creatinine level > 1.2 mg/dL, a platelet count <= 60,000/mL,
      a Model for End-Stage Liver Disease (MELD) score > 15, Child-Turcotte-Pugh class
      B or C, ascites, or portal vein thrombosis. Hepatotoxicity was defined as new or
      worsening ascites, encephalopathy, or grade 3 or 4 toxicity (bilirubin, aspartate
      aminotransferase, alanine aminotransferase, creatinine, or INR) according to the
      National Cancer Institute Common Terminology Criteria for Adverse Events. The
      rate and risk factors for death or urgent liver transplantation within 6 weeks of
      TACE and irreversible hepatotoxicity were determined with a generalized
      estimating equation analysis. Reversible hepatotoxicity developed after 90
      procedures (20%) in 78 patients (31%). Irreversible hepatotoxicity developed
      after 41 procedures (9%) in 37 patients (15%). Six patients (2%) underwent urgent
      liver transplantation, and 11 (4%) died within 6 weeks of TACE. Patients at
      increased risk for procedure-related mortality or urgent liver transplantation
      within 6 weeks of TACE had a baseline serum bilirubin level >= 4.0 mg/dL (P =
      0.01), an elevated INR (P < 0.001), hypoalbuminemia with an albumin level < 2.0
      g/L (P = 0.01), a serum creatinine level > 2.0 mg/dL (P = 0.02), large ascites (P
      = 0.002), encephalopathy (P = 0.005), or a MELD score >= 20 (P < 0.001). In
      conclusion, TACE can be performed safely in patients with baseline hepatic
      dysfunction. However, a poor hepatic reserve increases the risk of irreversible
      hepatotoxicity, which may lead to death or the need for urgent liver
      transplantation.

PMID- 23008092
TI  - Myocardial T2-mapping and velocity mapping: changes in regional left ventricular
      structure and function after heart transplantation.
AB  - Monitoring post cardiac transplant (TX) status relies on frequent invasive
      techniques such as endomyocardial biopsies and right heart cardiac
      catheterization. The aim of this study was to noninvasively evaluate regional
      myocardial structure, function, and dyssynchrony in TX patients. Myocardial T2
      mapping and myocardial velocity mapping of the left ventricle (basal,
      midventricular, and apical short-axis locations) was applied in 10 patients after
      cardiac transplantation (49 +/- 13 years, n = 2 with signs of mild rejection,
      time between TX and MRI = 1-64 months) and compared to healthy controls (n = 20
      for myocardial velocity mapping and n = 14 for T2). Segmental analysis based on
      the 16-segment American Heart Association model revealed increased T2 (P =
      0.0003) and significant (P < 0.0001) reductions in systolic and diastolic radial
      and long-axis peak myocardial velocities in TX patients without signs of
      rejection compared to controls. Multiple comparisons of individual left
      ventricular segments demonstrated reductions of long-axis peak velocities in 50%
      of segments (P < 0.001) while segmental T2 values were not significantly
      different. Systolic radial as well as diastolic radial and long-axis dyssynchrony
      were significantly (P < 0.04) increased in TX patients indicating less
      coordinated contraction, expansion, and lengthening. Correlation analysis
      revealed moderate but significant (P < 0.010) inverse relationships between
      myocardial T2 and long-axis peak velocities suggesting a structure-function
      relationship between altered T2 and myocardial function.

PMID- 23008093
TI  - Outcomes following transoral robotic surgery: supraglottic laryngectomy.
AB  - OBJECTIVES/HYPOTHESIS: To describe a single center outcomes following transoral
      robotic surgery for supraglottic laryngectomy (TORS-SL). STUDY DESIGN:
      Prospective data collection. METHODS: Patient records receiving TORS-SL for
      squamous cell carcinoma (SCCA) with at least 12 months follow-up fit inclusion
      for this study. Two patients with previous SCCA were excluded. RESULTS: 18
      patients (14 male, 4 female) were included in the study, having a mean follow-up
      time of 28.1 months (SD = 12.1). All patients had negative margins confirmed on
      final pathology. Nine (50%) patients received postoperative chemoradiation
      therapy for advanced neck disease. No (0%) patients received tracheostomy or
      gastrostomy tubes. There were no (0%) local recurrences, and three (16.7%)
      regional recurrences. Five (27.8%) patients experienced temporary postoperative
      complications. Overall 2-year outcomes reached 83%, 100%, and 89% for
      locoregional control, disease-specific survival, and overall survival
      respectively. CONCLUSIONS: Initial outcomes for TORS-SL are encouraging and are
      comparable to previously described treatment modalities. Larger studies are
      encouraged.

PMID- 23008094
TI  - Uncoupling protein 2 expression affects androgen synthesis in polycystic ovary
      syndrome.
AB  - The roles of uncoupling protein-2 (UCP2) on the androgen synthesis of granulosa
      cells derived from patients with polycystic ovary syndrome (PCOS) and normal
      subjects were explored. Primary human granulosa cells from 18 patients who
      received in vitro fertilization (IVF) were examined; nine patients had PCOS with
      hyperandrogenism. Primary cultures were treated with genipin, a proton leak
      inhibitor, guanosine diphosphate (GDP), an UCP inhibitor, and triiodothyronine
      (T3), an inducer of UCP gene expression. Mitochondrial membrane potential was
      determined using the JC-1 assay. T3 induced P450scc and UCP2 expressions and
      testosterone synthesis in both normal and PCOS granulosa cells. Their expressions
      in response to T3 treatments were correlated in the PCOS group. Differences in
      testosterone synthesis were observed between normal and PCOS cells in response to
      genipin. Increased mitochondrial membrane potential was observed in response to
      genipin and GDP; while T3 decreased it. Increased ovarian UCP2 expression in
      response to T3 treatment in PCOS may alter pregnenolone synthesis by influencing
      P450scc expression, thus altering testosterone production. Further in vivo
      studies are necessary to fully elucidate the role of UCP2 in the hyperandrogenism
      commonly observed in PCOS.

PMID- 23008095
TI  - Pituitary metastasis of thyroid cancer.
AB  - Pituitary metastases (PM) from thyroid cancer are rare, but their management can
      represent a difficult challenge for the endocrinologist. Our aim was to review
      all reported cases of PM from thyroid cancer. PubMed was consulted and 19 papers
      reporting 20 cases were found. We moreover discuss two of our own cases, which
      had come to our attention within a few months of one another. Eleven cases were
      follicular cancer, eight cases were papillary cancer, two cases were medullary
      cancer, and one case was an insular cancer. In nine cases, PM was the first sign
      of the disease. Cranial nerve involvement was the most common sign of its
      presence, and no neuroradiological imaging could lead to a sure diagnosis of PM.
      Neurosurgical intervention was performed in almost all cases, and post-surgical
      treatment comprised radioiodine, external beam radiotherapy, and radiosurgery.
      Prognosis was poor for larger metastases, cranial nerve palsy disappeared in only
      one case, and in only one case of intrasellar metastasis was the disease cured.
      PM from thyroid cancer are rare, but are burdened by a poor prognosis. An early
      diagnosis appears important, and a comprehensive strategy for treatment
      (neurosurgery, radioiodine, external radiotherapy, and radiosurgery) appears
      advisable.

PMID- 23008096
TI  - Bioinspired bioadhesive polymers: dopa-modified poly(acrylic acid) derivatives.
AB  - The one-step synthesis and characterization of novel bioinspired bioadhesive
      polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of
      certain gastropods, is reported. The novel polymers consist of combinations of
      either of two polyanhydride backbones and one of three amino acids,
      phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa-grafted
      hydrophobic backbone polymers exhibit as much as 2.5 * the fracture strength and
      2.8 * the tensile work of bioadhesion of a commercially available poly(acrylic
      acid) derivative as tested on live, excised, rat intestinal tissue.

PMID- 23008099
TI  - Lack of enantioselectivity in the SULT1A3-catalyzed sulfoconjugation of
      normetanephrine enantiomers: an in vitro and computational study.
AB  - (1R)-Normetanephrine is the natural stereoisomeric substrate for sulfotransferase
      1A3 (SULT1A3)-catalyzed sulfonation. Nothing appears known on the
      enantioselectivity of the reaction despite its potential significance in the
      metabolism of adrenergic amines and in clinical biochemistry. We confronted the
      kinetic parameters of the sulfoconjugation of synthetic (1R)-normetanephrine and
      (1S)-normetanephrine by recombinant human SULT1A3 to a docking model of each
      normetanephrine enantiomer with SULT1A3 and the 3'-phosphoadenosine-5'
      phosphosulfate cofactor on the basis of molecular modeling and molecular dynamics
      simulations of the stability of the complexes. The K(M), V(max), and k(cat)
      values for the sulfonation of (1R)-normetanephrine, (1S)-normetanephrine, and
      racemic normetanephrine were similar. In silico models were consistent with these
      findings as they showed that the binding modes of the two enantiomers were almost
      identical. In conclusion, SULT1A3 is not substrate-enantioselective toward
      normetanephrine, an unexpected finding explainable by a mutual adaptability
      between the ligands and SULT1A3 through an "induced-fit model" in the catalytic
      pocket.

PMID- 23008100
TI  - Re: Effect of letrozole on uterine artery Doppler flow indices prior to first
      trimester termination of pregnancy: a randomized controlled trial. V. C. Y. Lee,
      T. W. Y. Yeung, O. S. Tang, E. H. Y. Ng, W. S. B. Yeung and P. C. Ho. Ultrasound
      Obstet Gynecol 2012; 40: 392-397.

PMID- 23008097
TI  - Multiscale models of breast cancer progression.
AB  - Breast cancer initiation, invasion and metastasis span multiple length and time
      scales. Molecular events at short length scales lead to an initial tumorigenic
      population, which left unchecked by immune action, acts at increasingly longer
      length scales until eventually the cancer cells escape from the primary tumor
      site. This series of events is highly complex, involving multiple cell types
      interacting with (and shaping) the microenvironment. Multiscale mathematical
      models have emerged as a powerful tool to quantitatively integrate the convective
      diffusion-reaction processes occurring on the systemic scale, with the molecular
      signaling processes occurring on the cellular and subcellular scales. In this
      study, we reviewed the current state of the art in cancer modeling across
      multiple length scales, with an emphasis on the integration of intracellular
      signal transduction models with pro-tumorigenic chemical and mechanical
      microenvironmental cues. First, we reviewed the underlying biomolecular origin of
      breast cancer, with a special emphasis on angiogenesis. Then, we summarized the
      development of tissue engineering platforms which could provide high-fidelity ex
      vivo experimental models to identify and validate multiscale simulations. Lastly,
      we reviewed top-down and bottom-up multiscale strategies that integrate
      subcellular networks with the microenvironment. We present models of a variety of
      cancers, in addition to breast cancer specific models. Taken together, we expect
      as the sophistication of the simulations increase, that multiscale modeling and
      bottom-up agent-based models in particular will become an increasingly important
      platform technology for basic scientific discovery, as well as the identification
      and validation of potentially novel therapeutic targets.

PMID- 23008101
TI  - Re: Early pregnancy screening for hypertensive disorders in women without a
      priori high risk. A. Abdelaziz, M. A. Maher, T. M. Sayyed, M. F. Bazeed, N. S.
      Mohamed. Ultrasound Obstet Gynecol 2012; 40: 398-405.

PMID- 23008102
TI  - Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin
      pregnancies.
AB  - OBJECTIVES: Previous studies on singleton pregnancies have indicated that
      progestogens may reduce the rate of cervical shortening during pregnancy. The aim
      of this study was to investigate whether treatment with 17-alpha
      hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in
      twin pregnancies. METHODS: This was a secondary analysis of patients who had
      participated in a multicenter randomized clinical trial on the effectiveness of
      17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial).
      We included all trial participants with a twin gestation who had undergone repeat
      cervical length measurements during pregnancy. We performed a separate analysis
      of women with repeat measurements in centers where this was standard protocol for
      multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group
      and the placebo group was analyzed using a linear mixed model. RESULTS: Of the
      671 patients who participated in the trial, 282 (42%) had a twin pregnancy and
      underwent two or more cervical length measurements. Of these women, 140 were
      monitored in centers where repeat measurements were standard protocol. We
      observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to
      30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length
      decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for
      the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical
      length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95%
      CI, 1.08-1.21). CONCLUSION: In women with a twin pregnancy, there is progressive
      shortening of the cervix during pregnancy, regardless of 17-OHPC use.

PMID- 23008103
TI  - Non-invasive prenatal diagnosis for Down syndrome: no paradigm shift, just better
      testing... and it is already here!

PMID- 23008105
TI  - Progestogen safety: implications for meta-analysis.

PMID- 23008107
TI  - Report on the 11th World Congress in Fetal Medicine, 24-28 June 2012, Kos,
      Greece.

PMID- 23008108
TI  - Characterization of insulin-producing cells derived from PDX-1-transfected neural
      stem cells.
AB  - Islet cell transplantation is a promising treatment strategy for type-1 diabetes.
      However, functional islet cells are hard to obtain for transplantation and are in
      short supply. Directing the differentiation of stem cells into insulin-producing
      cells, which serve as islet cells, would overcome this shortage. Bone marrow
      contains hematopoietic stem cells and mesenchymal stem cells. The present study
      used bone marrow cells isolated from rats and neural stem cells (NSCs) that were
      derived from bone marrow cells in culture. Strong nestin staining was detected in
      NSCs, but not in bone marrow stromal cells (BMSCs). In vitro transfection of the
      pancreatic duodenal homeobox-1 (PDX-1) gene into NSCs generated insulin-producing
      cells. Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked
      immunosorbent assay (ELISA) analysis confirmed that PDX-1-transfected NSCs
      expressed insulin mRNA and released insulin protein. However, insulin release
      from PDX-1-transfected NSCs did not respond to the challenge of glucose and
      glucagon-like peptide-1. These results support the use of bone marrow-derived
      NSCs as a renewable source of insulin-producing cells for autologous
      transplantation to treat type-1 diabetes.

PMID- 23008109
TI  - Therapy of radiation-induced angiosarcoma of the breast in an elderly patient.

PMID- 23008110
TI  - A new look at tamoxifen: co-administration with letrozole in intrauterine
      insemination cycles.
AB  - OBJECTIVE: To assess the effectiveness of tamoxifen administration with letrozole
      in the context of intrauterine insemination (IUI) cycles. MATERIALS AND METHODS:
      This prospective double-blinded study included 130 patients. After randomization,
      65 patients in group A received letrozole + tamoxifen and human menopausal
      gonadotropin (HMG), whereas 65 patients in group B received placebo instead of
      tamoxifen. In both groups, the parameters recorded were total number of follicles
      with >=16 and 18 mm diameter, endometrial thickness and appearance, and total HMG
      administered. The results were compared between groups after single-stage IUI was
      performed. RESULTS: Total dominant follicles in both groups were similar (mean
      number of follicles with diameter >=16 and 18 mm was 1.5 +/- 1.4 and 1.6 +/- 1.1,
      respectively, in group A and 1.5 +/- 1.1 and 1.6 +/- 1, respectively, in group B;
      at the same time with less HMG usage in group A (255 +/- 167 vs. 313 +/- 174 IU),
      and higher pregnancy rate in group A (18.7 vs. 11.7 %); but none of them was
      statistically significant). Surprisingly, endometrial thickness was significantly
      higher in group A (7.7 +/- 1.5 vs. 7 +/- 1.3 mm; P value 0.008). CONCLUSION: In
      addition to the efficacy of tamoxifen in co-administration with clomiphene
      citrate, it has promising effects with letrozole in induction of ovulation cycles
      with or without IUI.

PMID- 23008111
TI  - Successful treatment of uterine prolapse by abdominal hysteropexy performed
      during cesarean section.
AB  - PURPOSE: Uterine prolapse complicating pregnancy is extremely rare. This report
      presents the surgical correction of uterine prolapse during cesarean section.
      CASE: We report a case of a 33-year-old woman with twin gestation who admitted to
      obstetric clinic with labor pain and total uterine prolapse at 33 weeks of
      gestation. An emergent cesarean section was performed for the indication of acute
      fetal distress. At the same operation, following cesarean delivery, abdominal
      hysteropexy using rectus fascia strips was performed successfully. On control
      performed 6 months later, patient was examined and it was detected uterine
      prolapse had regressed and babies were uneventful. CONCLUSION: This surgical
      method offers effective treatment of uterine prolapse.

PMID- 23008112
TI  - The assessment of intracranial dynamics by transcranial Doppler sonography in
      perioperative period in paediatric hydrocephalus.
AB  - PURPOSE: To evaluate Doppler parameters of anterior cerebral artery (ACA) and
      relationship to morphological parameters of cerebral ventricles and
      periventricular brain tissue in paediatric hydrocephalus before and after
      drainage procedure. METHODS: Forty newborns with hydrocephalus were evaluated
      before and after the drainage procedure. The morphological parameters of brain
      (ventricular index, width of ventricles, haemorrhagic lesions, asymmetric
      ventricular dilatation and dynamics of ventricles) were measured by transcranial
      ultrasonography. The haemodynamic parameters of ACA (peak systolic blood flow
      velocity, end-diastolic blood flow velocity and resistance index/RI/) were
      evaluated by Doppler ultrasonography. The correlation between morphological and
      haemodynamic parameters was analysed. RESULTS: We found significant decrease of
      ventricular dilatation, which was accompanied with significant decrease of basal
      and compressive RI-ACA after drainage procedure. The correlation between basal RI
      ACA, compressive RI-ACA and the dynamics of ventricular dilatation was not
      significant before and after drainage operation, as well. The significant
      correlation between preoperative basal RI-ACA, postoperative compressive RI-ACA
      and asymmetry of cerebral ventricles was confirmed. Statistical analysis showed
      significant correlation between basal RI-ACA, compressive RI-ACA and haemorrhagic
      lesions after drainage operation. CONCLUSIONS: The results of our study showed
      the alteration of Doppler parameters of cerebral circulation in newborns with
      hydrocephalus before the drainage procedure. The successful drainage operation
      leads to the improvement of haemodynamic parameters of cerebral circulation.
      However, the statistical analysis showed the influence of some intracranial
      factors-the asymmetry of dilatation of lateral cerebral ventricles and
      periventricular haemorrhagic lesions on the Doppler parameters of cerebral
      circulation.

PMID- 23008113
TI  - Identification of factors predictive of malignancy in patients with atypical
      biliary brushing results obtained via ERCP.
AB  - Biliary brushings obtained during ERCP can have one of three cellular
      interpretations: benign, malignant, or "atypical." Atypical interpretations
      usually result in further testing, and may cause controversy over management and
      increases in cost. We evaluated a large cohort of patients with atypical biliary
      brushings for analysis and risk stratification. All biliary brushing specimens
      collected between January 1, 2001 and December 31, 2010 that had an atypical
      result were included. Hospital electronic records were reviewed for these
      patients to include: demographics, indication for ERCP, endoscopist/pathologist
      impressions, serologic testing, stricture site, and information relating to the
      final clinical diagnosis. Eighty-six patients were included. Totally, 60/86
      patients (70%) had malignancies while 26/86 (30%) had no evidence of malignancy
      during long term follow up. Univariate analysis showed that the risk of malignant
      outcomes was significantly associated with older age, suspicious/malignant
      endoscopic impression, pancreatic mass, indications including jaundice and/or
      dilated bile ducts, stricture location within the common bile duct, PSC, and CA
      19-9 levels >300 U/mL. We created a novel scoring system for prediction of
      malignancy based on clinical and endoscopic factors. We identified parameters
      that are typically available to the clinician to categorize patients with an
      "atypical" bile duct brushing results into "high risk" and "lower risk"
      classifications. Our proposed scoring system would allow such risk stratification
      to take place.

PMID- 23008114
TI  - The biological regulation of ABCE1.
AB  - ATP binding cassette E1 (ABCE1) protein, also named RLI or HP68, is one member of
      ATP binding cassette superfamily. By forming a heterodimer with RNase L, ABCE1
      protein inhibits the IFN-depended 2-5A/RNase L system and regulates a broad range
      of biological functions including viral infection, tumor cell proliferation, and
      antiapoptosis. As a highly conserved protein, recent studies have mainly focused
      that ABCE1 protein is involving in the fields of HIV virus capsids assembly and
      important roles in translation. Our manuscript will review the studies which
      revealed the biological regulation of ABCE1.

PMID- 23008115
TI  - Loop-linker PCR: an advanced PCR technique for genome walking.
AB  - In this article, we developed a novel PCR method, termed loop-linker PCR, to
      isolate flanking sequences in transgenic crops. The novelty of this approach is
      its use of a stem-loop structure to design a loop-linker adapter. The adapter is
      designed to form a nick site when ligated with restricted DNA. This modification
      not only can prevent the self-ligation of adapters but also promotes the
      elongation of the 3' end of the loop-linker adapter to generate a stem-loop
      structure in the ligation products. Moreover, the suppressive effect of the stem
      loop structure decreases nonspecific amplification and increases the success rate
      of the approach; all extension products will suppress exponential amplification
      except from the ligation product that contains the specific primer binding site.
      Using this method, 442, 1830, 107, and 512 bp left border flanking sequences were
      obtained from the transgenic maizes LY038, DAS-59122-7, Event 3272, and the
      transgenic soybean MON89788, respectively. The experimental results demonstrated
      that loop-linker PCR is an efficient, reliable, and cost-effective method for
      identifying flanking sequences in transgenic crops and could be applied for other
      genome walking applications.

PMID- 23008117
TI  - Impact of estimated liver volume and liver weight on gender disparity in liver
      transplantation.
AB  - Although lower Model for End-Stage Liver Disease (MELD) scores due to lower
      levels of serum creatinine in women might account for some of the gender
      disparity in liver transplantation (LT) rates, even within MELD scores, women
      undergo transplantation at lower rates than men. It is unclear what causes this
      disparity, but transplant candidate/donor liver size mismatch may be a factor. We
      analyzed Organ Procurement and Transplantation Network data for patients with end
      stage liver disease on the waiting list. A pooled conditional logistic regression
      analysis was used to assess the association between gender and LT and to
      determine the degree to which this association was explained by lower MELD scores
      or liver size. In all, 28,866 patients and 424,001 person-months were included in
      the analysis. The median estimated liver volume (eLV) and the median estimated
      liver weight (eLW) were significantly lower for women versus men on the LT
      waiting list (P < 0.001). When we controlled for the region and the blood type,
      women were 25% less likely to undergo LT in a given month in comparison with men
      (P < 0.001). When the MELD score was included in the model, the odds ratio (OR)
      for gender increased to 0.84, and this suggested that 9 percentage points of the
      25% gender disparity were due to the MELD score. When eLV was added to the model,
      there was an additional 3% increase in the OR for gender, and this suggested that
      transplant candidate/donor liver size mismatch was an underlying factor for the
      lower LT rates in women versus men (OR = 0.87, P < 0.001). In conclusion, lower
      LT rates among women on the waiting list can be explained in part by lower MELD
      scores, eLVs, and eLWs in comparison with men. However, at least half of the
      gender disparity still remains unexplained.

PMID- 23008118
TI  - Chemopreventive efficacy of green tea drinking against 1,2-dimethyl hydrazine
      induced rat colon carcinogenesis.
AB  - Colorectal cancer is one of the leading causes of tumour-related deaths. In the
      present study, the chemopreventive effect of green tea on 1,2-dimethylhydrazine
      (DMH)-induced colon carcinogenesis was studied in male Wistar rats. The DMH group
      received subcutaneous injections of DMH (30 mg kg(-1) body weight) once a week
      for 30 weeks, the normal group received the vehicle of DMH, and the DMH + green
      tea group received DMH simultaneously with 1% green tea as their sole source of
      drinking fluid throughout the experimental period. In the DMH group treated with
      green tea, significant reductions in gene overexpressions of colonic nuclear
      factor kappaB (NF-kappaB), tumour necrosis factor alpha, inducible nitric oxide
      synthase and cyclooxygenase 2, and NF-kappaB immunostaining indicates the anti
      inflammatory effect of green tea in attenuating colon cancer. Moreover, the anti
      angiogenic and anti-invasiveness effects of green tea were revealed as reductions
      of both vascular endothelial growth factor and matrix metalloproteinase-7 mRNA
      expression levels. These effects were confirmed by the significant reduction of
      serum tumour necrosis factor alpha, C-reactive protein levels, inhibition of
      tumour incidence, and nearly normal survival rate and colonic architecture. It
      can be concluded that green tea exerts a potent chemopreventive effect on colon
      carcinogenesis possibly due to the inhibition of NF-kappaB.

PMID- 23008119
TI  - A fabricated forearm free flap with accompanying phonation tube for simultaneous
      reconstruction of a pharyngolaryngeal circumferential defect and voice loss: new
      surgical modification with functional phonation outcome.
AB  - BACKGROUND: Total pharyngolaryngectomy is potentially ablative surgery, resulting
      in compromise of some most basic functions of life, including speech and
      swallowing. Tracheoesophageal puncture is the gold standard for voice
      restoration. But it still has prosthesis-related problems. OBJECTIVES/HYPOTHESIS:
      We designed a uniquely customized radial forearm free flap (RFFF), which also
      incorporated a region for phonation tube (PT) creation, for the dual purpose of
      circumferential laryngopharyngeal defect reconstruction and voice production.
      METHODS: From August 2005 to September 2010, there were 18 male patients with
      late-stage hypopharyngeal cancer (HPC) or laryngeal cancer (LC) who received one
      stage reconstruction with the fabricated RFFF-accompanying PT after total
      pharyngolaryngectomy. We recorded the phonation outcome of phonation efficacy
      (PE) and maximal phonation time (MPT) postoperatively within 1 month and at least
      1 year after surgery. RESULTS: Nine patients suffered from HPC and the others
      suffered from LC. Twelve patients received concurrent chemoradiotherapy after
      surgery. The follow-up time was 12 to 56 months (mean 28.7 months). There was no
      significant variance in the PE (79.72%, SD=21.93% vs. 62.50%, SD=39.60%,
      respectively; p = 0.115) and MPT (2.58 seconds, SD=1.80 vs. 2.97 seconds,
      SD=3.96, respectively; p = 0.878) between the first and last follow-up points,
      even when the patients were grouped by radiotherapy status after surgery or by
      disease group. CONCLUSIONS: The phonation outcome in our experience was
      satisfactory and it tolerated postoperative radiotherapy during at least the 12
      month follow-up period.

PMID- 23008121
TI  - Quantitative Bayesian model-based analysis of amide proton transfer MRI.
AB  - Amide Proton Transfer (APT) reports on contrast derived from the exchange of
      protons between amide groups and water. Commonly, APT contrast is quantified by
      asymmetry analysis, providing an ensemble contrast of both amide proton
      concentration and exchange rate. An alternative is to sample the off-resonant
      spectrum and fit an exchange model, permitting the APT effect to be quantified,
      correcting automatically for confounding effects of spillover, field
      inhomogeneity, and magnetization transfer. Additionally, it should permit amide
      concentration and exchange rate to be independently quantified. Here, a Bayesian
      method is applied to this problem allowing pertinent prior information to be
      specified. A three-pool model was used incorporating water protons, amide
      protons, and magnetization transfer effect. The method is demonstrated in
      simulations, creatine phantoms with varying pH and in vivo (n = 7). The Bayesian
      model-based approach was able to quantify the APT effect accurately (root-mean
      square error < 2%) even when subject to confounding field variation and
      magnetization transfer effect, unlike traditional asymmetry analysis. The in vivo
      results gave approximate APT concentration (relative to water) and exchange rate
      values of 3 * 10(-3) and 15 s(-1) . A degree of correlation was observed between
      these parameter making the latter difficult to quantify with absolute accuracy,
      suggesting that more optimal sampling strategies might be required.

PMID- 23008120
TI  - Coenzyme q10 ameliorates neurodegeneration, mossy fiber sprouting, and oxidative
      stress in intrahippocampal kainate model of temporal lobe epilepsy in rat.
AB  - Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and
      the most resistant type to treatment. Novel treatment approaches are strongly
      required to prevent or even reverse the cellular and molecular mechanisms of
      epileptogenesis. In this study, we investigated the possible neuroprotective
      effect of coenzyme Q10 (CoQ10) in an intrahippocampal kainate model of TLE in
      rat. Kainate injection caused a higher seizure severity during status epilepticus
      and spontaneous seizure phases, and CoQ10 pretreatment significantly attenuated
      its severity and incidence rate. Intrahippocampal kainate also led to elevation
      of malondialdehyde (MDA) and nitrite, and CoQ10 significantly attenuated the
      increased MDA and nitrite content. In addition, intrahippocampal kainate induced
      a significant degeneration of neurons in CA1, CA3, and hilar regions of the
      hippocampus, and CoQ10 significantly attenuated these changes in CA1 and CA3
      regions. Timm's staining data showed a robust mossy fiber sprouting (MFS) in
      dentate gyrus of kainate-lesioned rats and CoQ10 significantly lowered MFS
      intensity. These data suggest that CoQ10 pretreatment could attenuate spontaneous
      recurrent seizures and inhibit hippocampal neuronal loss and aberrant MFS in
      kainate-induced model of TLE in rat, and part of its beneficial effect is due to
      its potential to mitigate oxidative stress.

PMID- 23008122
TI  - Impact of an HIV prevention intervention on condom use among long distance
      truckers in India.
AB  - This paper examines the impact of three components of an HIV prevention program
      (mid-media, interpersonal communication, and project-run clinics) on consistent
      condom use by long distance truckers with paid and non-paid female partners in
      India. Data from 2,723 long distance truckers were analyzed using the propensity
      score matching approach. Based on utilization of services, the following
      categories of intervention exposure were derived: no exposure, exposure only to
      mid-media, exposure only to mid-media and interpersonal communication, exposure
      only to mid-media and project-run clinics, and exposure to all three intervention
      components. Compared to those who were not exposed to any intervention, exposure
      to mid-media alone increased consistent condom use with paid female partners by
      about ten percent. Exposure to mid-media and visits to project-run clinics
      increased consistent condom use with non-paid female partners by 26 %. These
      findings suggest that mid-media events and clinics were the most effective
      package of services to increase consistent condom use among the long distance
      truckers.

PMID- 23008123
TI  - Open, closed, or in between: relationship configuration and condom use among men
      who use the internet to seek sex with men.
AB  - Nearly 70 % of HIV+ men who have sex with men (MSM) are estimated to have
      contracted HIV from a main partner. We examine whether condom use varies by
      relationship configuration, including open relationships with and without
      cheating. 656 MSM in committed relationships were recruited through a sexually
      explicit social networking website. Of the 55 % of MSM who had anal sex with a
      non-main partner in the past 90 days, two-thirds did not use a condom. Adjusting
      for covariates, MSM in relationships characterized as open with cheating versus
      monogamous were more likely to have unprotected anal sex with both main and non
      main partners. MSM who perceived that their partner played around or cheated were
      more likely to have unprotected anal sex with a non-main partner. Prevention
      messages should attempt to reduce cheating and increase personal responsibility
      for protecting partners from HIV. Messages should be tailored to reflect open and
      monogamous relationships.

PMID- 23008124
TI  - Substance use predictors of poor medication adherence: the role of substance use
      coping among HIV-infected patients in opioid dependence treatment.
AB  - Many HIV-infected injection drug users (IDUs) continue to use illicit substances
      despite being in substance use treatment. Substance use is associated with non
      adherence to HIV medications; however underlying mechanisms regarding this
      relation are understudied. The current investigation examined the role of
      substance use coping in terms of the relation between substance use and HIV
      medication adherence. Participants were 121 HIV-infected IDUs (41 % female, M age
      = 47, SD = 7.1) in opioid dependence treatment. Participants completed self
      report questionnaires, were administered clinical interviews and oral toxicology
      screens, and used a medication-event-monitoring-system cap to assess 2 week HIV
      medication adherence. The use of cocaine and multiple substances were
      significantly related to decreased medication adherence. Substance use coping
      mediated these associations. Findings highlight the importance of assessing,
      monitoring, and targeting ongoing substance use, and ways to increase positive
      coping for HIV-infected IDUs in substance use treatment to aid in HIV medication
      adherence.

PMID- 23008127
TI  - Does lack of glottic closure affect quality of life as a cause of constipation in
      laryngectomized patients?
AB  - The permanent disappearance of glottic closure eventually causes inadequate
      defecatory propulsion resulting in functional constipation. The aim of this study
      is to reveal functional constipation probably induced by lack of glottic closure
      in laryngectomized patients. The study was conducted in a prospective, tertiary
      care center. Forty patients who had undergone total laryngectomy (study group)
      and 30 who had undergone microlaryngoscopic surgery (control group) were
      evaluated. Based on the European Organisation for Research and Treatment of
      Cancer, Quality of Life Questionnaires C30, the presence of functional
      constipation was investigated using the Rome II diagnostic criteria and was
      confirmed by measurement of colonic transit time using a radiopaque marker test.
      Functional constipation and colonic transit time were found to be increased and
      statistically significant in laryngectomized patients (70 %) compared with the
      control group (26 %) (p < 0.01). Functional constipation is more prevalent among
      laryngectomized patients. When evaluating quality of life of patients undergoing
      laryngectomy, colorectal functions must be taken into consideration.

PMID- 23008128
TI  - The role of allergy in the etiopathogenesis of idiopathic sudden sensorineural
      hearing loss.
AB  - To evaluate the role of allergy in the etiopathogenesis of sudden hearing loss
      using cytokine profile, allergic parameters, and lymphocyte subgroups, a total of
      31 patients aged between 30 and 62 years (mean age: 42.48 +/- 15.86 years) with
      the diagnosis of sudden hearing loss were enrolled in the study between 2008 and
      2011. The control group comprised 30 age-matched adult subjects accepted as
      clinically healthy individuals living in the same region with comparable
      socioeconomic parameters. The patient and the control group were questioned for
      history of allergy. Lymphocyte subgroups in the peripheral blood were evaluated
      using Becton-Dickinson monoclonal CD4, CD8, CD19, and CD23 antibodies. In the
      patient and control groups, the levels of IFN- gamma, IL4, IL10, and total IgE
      were measured and compared between the groups. Skin test was used for detection
      of inhaler allergens in the patient and the control groups, and specific IgE
      tests were performed using the RAST method for food allergens. The Spearman's rho
      correlation, the unpaired t test, the Mann-Whitney U test, and the Shapiro-Wilk
      test were used to determine the differences between the groups. The limit for
      statistical significance was p < 0.05. When the patient and the control group
      were compared, the differences between CD4, CD23, IL4, IL10, and IgE were
      statistically significant. On analyses of the patients' serum samples, strongly
      positive correlations were determined between IgE and CD23, IL10, IL4; IL4 and
      IL10, CD23, CD4; IL10 and CD23, CD4 (Spearman rho, p = 0.000), while a weakly
      positive correlation was found between IgE and CD4 (Spearman rho, p = 0.020). A
      correlation between IFN-gamma and CD4 was weakly negative (Spearman rho, p =
      0.040). The total IgE levels were estimated to be above the normal reference
      ranges (0-100 IU/ml) in 25.8 % of the cases in the patient group. History of
      allergy was found in 61.9 % of the patients. The results of this study
      substantiate the role of allergy in the etiopathogenesis of sudden hearing loss.
      We think that during the diagnostic work-up of these patients allergy should be
      interrogated seriously, necessary tests should be performed, and allergy should
      be considered in the decision-making process of the treatment of sudden hearing
      loss.

PMID- 23008129
TI  - Neck metastases in oropharyngeal cancer: Necessity and extent of bilateral
      treatment.
AB  - BACKGROUND: Bilateral neck treatment in oropharyngeal squamous cell carcinoma
      (OPSCC) is controversial. This study determined the rate of bilateral neck
      metastases in OPSCC and formulated a neck treatment algorithrm for OPSCC.
      METHODS: In all, 212 consecutive patients with OPSCC underwent ipsilateral level
      I-V and contralateral I-III or I-V neck dissections. Pathology results were used
      to identify factors predicting bilateral neck metastases. RESULTS: A total of 171
      patients (81%) had ipsilateral and 41 patients (24%) bilateral neck metastases.
      Multivariate logistic regression found cT4 and >=cN2a significantly associated
      with contralateral neck metastases (p < .05). However, tumor site was not
      predictive (p > .05). High-risk pathology features predicted contralateral neck
      disease (p < .05). cN0 and cN1 necks were unlikely to harbor disease in level V
      (<5%). Both 2- and 5-year contralateral neck recurrence rates were 1% and 2%.
      CONCLUSIONS: Bilateral neck disease in OPSCC is more common than once thought.
      Patients with OPSCC with cT4 or cN2a+ would benefit from bilateral neck
      treatment. Posttreatment high-risk features should guide treatment escalation.

PMID- 23008130
TI  - Primary hydatid cyst of the supraspinatus muscle: complete removal of the
      germinal layer and cytodiagnosis by fine-needle aspiration.
AB  - Primary hydatid disease of the skeletal muscle without systemic involvement is
      rare. The purpose of this report is to document the novel clinical presentation
      and the interesting facets of fine-needle aspiration in a case of hydatid
      disease. It was a case of primary hydatid cyst of the left supraspinatus muscle
      in an Indian woman living in Kuwait, which was clinically diagnosed as a lipoma.
      Fine-needle aspiration (FNA) yielded 2 ml of clear fluid with white particulate
      material. The cytocentrifuged smears prepared from the aspirated fluid showed
      many scolices, occasional laminated cyst wall fragments and numerous hooklets.
      The laminated cyst wall and scolices were PAS positive. Trichrome staining
      imparted a demon-head-like appearance to the scolices. The cytodiagnosis of
      hydatid cyst was corroborated by histopathological examination of an excised
      whitish membrane and an irregular cystic fragment, which showed parallel
      laminations without germinal layer, and skeletal muscle with granulomas and a
      dense eosinophilic infiltration, respectively. Quantitative serological (indirect
      hemagglutination) test on blood sample collected 9 days after the excision of the
      cyst showed insignificant antibody titer to Echinococcus sp. and after 6 weeks
      the antibodies were completely absent. CT scan of the chest and abdomen performed
      7 weeks after removal of cyst showed no evidence of visceral hydatid cyst.

PMID- 23008131
TI  - Effect of recombinant adeno-associated BMP-4/7 fusion gene on the biology of
      BMSCs.
AB  - The aim of the study was to investigate the effect of recombinant adeno
      associated virus (AAV) with morphogenetic protein 4/7 fusion gene on the
      ossification of rabbit bone marrow stromal cells (BMSCs). The genes BMP-4 and BMP
      7 were obtained through one-step reverse transcriptase polymerase chain reaction
      from human placental cells. The BMP-4/7 fusion gene was generated through
      recombination. The rabbit BMSCs were transfected with the recombinant AAV vectors
      carrying AAV-BMP-4/7 with various multiplicity of infection (MOI) values.
      Expression of fusion gene BMP-4/7 protein was determined by the ELISA method. The
      ossification of cells was evaluated by observing alkaline phosphatase (ALP) and
      osteocalcin (OC) activity after transfection for 7 and 14 days. We successfully
      constructed the recombinant AAV with the BMP-4/7 fusion gene. A 29-20 kDa protein
      was shown by SDS-PAGE electrophoresis following transfection with AAV-BMP-4/7.
      The fusion protein BMP-4/7 in BMSCs transferred by AAV showed a positive
      correlation with various MOI values. There was significantly higher ALP and OC
      activity in the AAV-BMP-4/7 transfection groups than in the AAV-EGFP groups
      (t(ALP)=896.88, P<0.001, t(OC)=543.24, P<0.01). The fusion gene BMP-4/7 is
      capable of enhancing the expression of BMPs and possesses significant
      ossification activity through AAV.

PMID- 23008132
TI  - Interleukin-28B polymorphism in hepatitis C and liver transplantation.
AB  - The discovery of interleukin-28B (IL-28B) single-nucleotide polymorphisms has
      opened an important new area of research in liver transplantation (LT) for
      hepatitis C virus (HCV). Both recipient- and donor-derived IL-28B genotypes
      affect the post-LT treatment response, with sustained virological response (SVR)
      rates oscillating from >50% in homozygotes for the favorable allele (up to 90%
      when this is present in both the recipient and the donor) to <15% in homozygotes
      for the unfavorable allele and from 30% to 50% in heterozygotes. Other key
      posttransplant outcomes affected by the IL-28B genotype are the time to
      histological recurrence, HCV RNA and alanine aminotransferase levels,
      histological variables (including the rate of fibrosis progression), and
      hepatocellular carcinoma. Interactions between donor and recipient IL-28B
      genotypes are complex and may affect outcomes not directly related to HCV
      infections, such as acute cellular rejection (ACR) and metabolic diseases. A
      preferential allocation system in which livers from donors homozygous for the
      favorable allele are given to HCV patients might be postulated to improve SVR
      rates and post-LT outcomes in recipients with HCV infections (a 25% increase in
      SVR and an 8% decrease in mortality at 5 years). Although negative effects from
      this are difficult to predict, they could include an accelerated progression of
      fibrosis in patients with failed HCV eradication and an increase in ACR in non
      HCV patients. Our knowledge of the precise role of IL-28B genotypes in the course
      of post-LT HCV is evolving, but existing knowledge suggests the possibility of
      exploring strategies that use IL-28B genotyping to reduce the impact of post-LT
      adverse outcomes.

PMID- 23008133
TI  - Isocaloric intake of a high-fat diet promotes insulin resistance and inflammation
      in Wistar rats.
AB  - The aim of this study was to investigate the effect of isocaloric intake from a
      high-fat diet (HFD) on insulin resistance and inflammation in rats. Male Wistar
      rats were fed on an HFD (n = 12) or control diet (n = 12) for 12 weeks.
      Subsequently, all animals were euthanized, and blood glucose, insulin, free fatty
      acids, C-reactive protein, lipid profile, cytokines and hepatic-enzyme activity
      were determined. Carcass chemical composition was also analyzed. During the first
      and the twelfth weeks of the experimental protocol, the oral glucose tolerance
      test and insulin tolerance test were performed and demonstrated insulin
      resistance (P < 0.05) in the HFD group. Although food intake (g) was lower (P <
      0.05) in the HFD group compared with the control group, the concentration of
      total cholesterol, low-density lipoprotein, C-reactive protein and liver weight
      were all significantly higher. The kinase inhibitor of kappaB, c-Jun N-terminal
      kinase and protein kinase B expressions were determined in the liver and skeletal
      muscle. After an insulin stimulus, the HFD group demonstrated decreased (P =
      0.05) hepatic protein kinase B expression, whereas the kinase inhibitor of kappaB
      phospho/total ratio was elevated in the HFD muscle (P = 0.02). In conclusion, the
      isocaloric intake from the HFD induced insulin resistance, associated with
      impaired insulin signalling in the liver and an inflammatory response in the
      muscle.

PMID- 23008134
TI  - ECG and echocardiographic findings in 10-15-year-old elite athletes.
AB  - BACKGROUND: Data on electrocardiographic and echocardiographic pre-participation
      screening findings in paediatric athletes are limited. METHODS AND RESULTS: 10-
      15 year-old athletes (n = 343) were screened using electro- and echocardiography.
      The electrocardiogram (ECG) was normal in 220 (64%), mildly abnormal in 108
      (31%), and distinctly abnormal in 15 (4%) athletes. Echocardiographic upper
      reference limits (URL, 97.5 percentile) for the left ventricular (LV) wall
      thickness in 10-11-year-old boys and girls were 9-10 mm and 8-9 mm, respectively;
      in 12-13-year-old boys and girls 9-10 mm; and in 14-15-year-old boys and girls 10
      11 mm and 9-10 mm, respectively. Three athletes were excluded from competitive
      sports: one for symptomatic Wolff-Parkinson-White syndrome with a normal
      echocardiogram; one for negative T-waves in V1-V4 and a dilated right ventricle
      by echocardiography suggestive of (arrhythmogenic) right ventricular disease; and
      one for normal ECG and biscupid aortic valve including an aneurysm of the
      ascending aorta detected by echocardiography. Related to echocardiographic
      findings, the sensitivity and specificity of the ECG to identify cardiovascular
      abnormalities was 38% and 64%, respectively. The ECG's positive-predictive and
      negative-predictive values were 13% and 88%, respectively. The numbers needed to
      screen and calculated costs were 172 for ECG (?7049), 172 for echocardiography
      (?11,530), and 114 combining ECG and echocardiography (?9323). CONCLUSIONS:
      Compared to adults, paediatric athletes presented with fewer distinctly abnormal
      ECGs, and there was no gender difference in paediatric athletes' ECG-pattern
      distribution. A combination of ECG and echocardiography for pre-participation
      screening of paediatric athletes is superior to ECG alone but 30% more costly.

PMID- 23008135
TI  - Type D personality is associated with increased prevalence of ventricular
      arrhythmias in community-residing persons without coronary heart disease.
AB  - BACKGROUND: Type D personality may be a risk factor for poor outcome in patients
      with cardiovascular disease. The biological mechanisms underlying this
      association are poorly understood. The objective of the study was to test the
      hypotheses that Type D personality is associated with biological markers for
      sympathetic dysregulation. DESIGN: Cross-sectional community-based study.
      METHODS: Type D personality was evaluated by DS-14 in 450 persons (46% men), aged
      between 30 and 65 years. From a Holter-recording, (mean length 18.3 hours), long
      term heart rate, ventricular arrhythmias, and heart rate variability (HRV) were
      registered as markers of sympathetic dysregulation. Traditional cardiovascular
      risk factors, apnoea-hypopnoea index, medication, and anxiety symptoms were
      adjusted for. RESULTS: Type D persons had higher long-term averaged heart rate
      (74 vs. 71 beats/min, p = 0.003), but this difference was attenuated and not
      significant in the multivariate model (p = 0.078)). There was an increased
      prevalence of complex ventricular ectopy (bigeminy, trigeminy, or non-sustained
      ventricular tachycardia; 14 vs. 6%, p = 0.005 in multivariate model). HRV indices
      did not differ significantly between those with or without Type D personality.
      Anxiety symptoms did not confound these associations. CONCLUSIONS: Type D
      personality is independently associated with a higher likelihood of ventricular
      arrhythmias, which may be implicated in the increased cardiovascular risk
      observed in persons with Type D personality.

PMID- 23008136
TI  - Structured smoking cessation training for health professionals on cardiology
      wards: a prospective study.
AB  - BACKGROUND: Smoking is a major cardiovascular risk factor, and smoking cessation
      is imperative for patients hospitalized with a cardiovascular event. This study
      aimed to evaluate a systems-based approach to helping hospitalized smokers quit
      and to identify implementation barriers. DESIGN: Prospective intervention study
      followed by qualitative analysis of staff interviews. METHODS: The prospective
      intervention study assessed the effects of implementing standard operating
      procedures (SOPs) for the provision of counselling and pharmacotherapy to smokers
      admitted to cardiology wards on counselling frequency. In addition, a qualitative
      analysis of staff interviews was undertaken to examine determinants of physician
      and nurse behaviour; this sought to understand barriers in terms of motivation,
      capability, and/or opportunity. RESULTS: A total of 150 smoking patients were
      included in the study (75 before and 75 after SOP implementation). Before the
      implementation of SOPs, the proportion of patients reporting to have received
      cessation counselling from physicians and nurses was 6.7% and 1.3%, respectively.
      Following SOP implementation, these proportions increased to 38.7% (p < 0.001)
      and 2.7% (p = 0.56), respectively. Qualitative analysis revealed that lack of
      motivation, e.g. role incongruence, appeared to be a major barrier. CONCLUSIONS:
      Introduction of a set of standard operating procedures for smoking cessation
      advice was effective with physicians but not nurses. Analysis of barriers to
      implementation highlighted lack of motivation rather than capability or
      opportunity as a major factor that would need to be addressed.

PMID- 23008137
TI  - Exercise-induced changes of left ventricular diastolic function in postmenopausal
      amateur marathon runners: assessment by echocardiography and cardiac biomarkers.
AB  - PURPOSE: Diastolic dysfunction is common among elderly women. Recently, concerns
      regarding marathon-induced myocardial damage were raised among young male
      runners. The goal of our study was to assess the impact of marathon running on
      systolic and diastolic ventricular function before and immediately after
      completing a marathon among postmenopausal well-trained amateur women. METHODS: A
      total of 89 female runners of the Berlin Marathon were included (35
      postmenopausal and 54 premenopausal female controls) and examined before,
      immediately, and 2 weeks after the race by echocardiography (including tissue
      Doppler- and 2D strain speckle tracking) and underwent blood tests. RESULTS:
      After the marathon, there was a significant increase in E/E' (postmenopausal 8.5
      +/- 2.3 vs. 10.9 +/- 3.2 post race; control: 8.1 +/- 1.8 vs. 9.9 +/- 2.9 post
      race, p < 0.001) and a decrease in E/A in both groups (postmenopausal 1.3 +/-
      0.36 vs. 0.9 +/- 0.21 post race; control 1.7 +/- 0.6 vs. 1.1 +/- 0.3; p < 0.001).
      In contrast, regardless of the hormonal status the atrial contraction increased
      significantly. Left and right ventricular systolic contractility, as assessed by
      speckle tracking and pulsed-wave tissue Doppler velocities, showed a significant
      increase in both groups. Of all runners, 55 (61.8%) experienced increases in
      troponin T and/or N-terminal-B-type natriuretic peptide after the race. All
      echocardiographic and laboratory parameters returned to normal within 2 weeks.
      CONCLUSIONS: 2D strain analysis of the left and right ventricles showed an acute
      improvement of the systolic function after marathon running in pre- and
      postmenopausal well-trained women. There were no long lasting detrimental effects
      on the diastolic function.

PMID- 23008138
TI  - Evidence-based surgical management of T1 or T2 temporal bone malignancies.
AB  - OBJECTIVES/HYPOTHESIS: To determine whether aggressive surgical management is
      more effective than local canal resection (LCR) for early-stage temporal bone
      malignancies. STUDY DESIGN: Retrospective study. METHODS: Forty-three cases of
      early-stage external auditory canal (EAC) carcinoma who received surgical
      management between 1993 and 2011 were reviewed. Preoperative computed tomography,
      enhanced magnetic resonance imaging, pure-tone audiometry, and biopsy were
      performed. Patients underwent either LCR or lateral temporal bone resection
      (LTBR). Postoperative pathologic examinations were conducted on all specimens,
      including assessment of margin status. The duration of the postoperative follow
      up period ranged from 6 months to 18 years. RESULTS: Of 26 patients who underwent
      LCR, 10 were stage T1 and 16 were T2. Positive surgical margins were identified
      in 14 patients. During the follow-up, 12 patients developed recurrence. Of 17
      patients who underwent LTBR with superficial parotidectomy, six were stage T1 and
      11 were T2. The lateral EAC margins were negative in all 17 patients. In 2/6 T1
      patients and in 5/11 T2 patients, tumor cells were identified deep within the EAC
      cartilage and parotid gland. All of the patients who underwent LTBR survived
      without evidence of recurrence. CONCLUSIONS: LTBR with superficial parotidectomy
      offers the greatest chance of cure for early-stage EAC carcinoma. Intraoperative
      frozen sections are necessary to determine the tumor-free lateral EAC margins.
      Postoperative radiotherapy is not strongly recommended for early-stage EAC
      carcinoma after LTBR.

PMID- 23008140
TI  - In vivo measurement of volumetric strain in the human brain induced by arterial
      pulsation and harmonic waves.
AB  - Motion-sensitive phase contrast magnetic resonance imaging and magnetic resonance
      elastography are applied for the measurement of volumetric strain and tissue
      compressibility in human brain. Volumetric strain calculated by the divergence
      operator using a biphasic effective-medium model is related to dilatation and
      compression of fluid spaces during harmonic stimulation of the head or during
      intracranial passage of the arterial pulse wave. In six volunteers, phase
      contrast magnetic resonance imaging showed that the central cerebrum expands at
      arterial pulse wave to strain values of (2.8 +/- 1.9).10(-4). The evolution of
      volumetric strain agrees well with the magnitude of the harmonic divergence
      measured in eight volunteers by magnetic resonance elastography using external
      activation of 25 Hz vibration frequency. Intracranial volumetric strain was
      proven sensitive to venous pressure altered by abdominal muscle contraction. In
      eight volunteers, an increase in volumetric strain due to abdominal muscle
      contraction of approximately 45% was observed (P = 0.0001). The corresponding
      compression modulus in the range of 9.5-13.5 kPa demonstrated that the
      compressibility of brain tissue at 25 Hz stimulation is much higher than that of
      water. This pilot study provides the background for compression-sensitive
      magnetic resonance imaging with or without external head stimulation. Volumetric
      strain may be sensitive to fluid flow abnormalities or pressure imbalances
      between vasculature and parenchyma as seen in hydrocephalus.

PMID- 23008139
TI  - The non-ossifying fibroma: a case report and review of the literature.
AB  - The non-ossifying fibroma (NOF) is a benign, non-neoplastic lesion most commonly
      seen in the metaphyses of the long bones in children. While rare, the NOF has
      been reported in the mandible. The NOF in the extra-gnathic skeleton has a
      characteristic radiographic appearance, is typically asymptomatic and has a
      variable histologic make-up. Correlation of the radiographic appearance, clinical
      presentation and histopathology allows for differentiation of the NOF from
      odontogenic and non-odontogenic cysts and tumors. We report a new case of this
      interesting entity and review the radiographic, clinical and histologic features
      of the gnathic NOF reported in the literature. A thorough search of the English
      language literature returned a total of 19 cases of NOF involving the gnathic
      bones.

PMID- 23008141
TI  - Recent advances in the development of semiconducting DPP-containing polymers for
      transistor applications.
AB  - This progress report summarizes the numerous DPP-containing polymers recently
      developed for field-effect transistor applications including diphenyl-DPP and
      dithienyl-DPP-based polymers as the most commonly reported materials, but also
      difuranyl-DPP, diselenophenyl-DPP and dithienothienyl-DPP-containing polymers. We
      discuss the hole and electron mobilities that were reported in relation to
      structural properties such as alkyl substitution patterns, polymer molecular
      weights and solid state packing, as well as electronic properties including HOMO
      and LUMO energy levels. We moreover consider important aspects of ambipolar
      charge transport and highlight fundamental structure-property relations such as
      the relationships between the thin film morphologies and the charge carrier
      mobilities observed for DPP-containing polymers.

PMID- 23008143
TI  - Endobronchial ultrasound-guided fine-needle aspiration cytology of bronchial low
      grade mucoepidermoid carcinoma: Rapid on-site evaluation of cytopathologic
      findings.
AB  - Bronchial mucoepidermoid carcinoma (MEC) is rare, comprising about 0.2% of
      primary lung tumors. Endobronchial ultrasound (EBUS) guided fine-needle
      aspiration (FNA) cytology is an integral tool in the diagnosis and staging of
      malignant lung tumors. Rapid on-site evaluation (ROSE) has been proven useful as
      a guide for assessing the adequacy and accuracy of the FNA samples. Therefore,
      comprehensive knowledge of diagnostic cytomorphologic findings of MEC is critical
      for ROSE. We reported a 46-year-old woman with 6 weeks of cough productive of
      yellow sputum that did not improve on antibiotics. A chest CT demonstrated a well
      circumscribed nodule in the right lower lobe bronchus that extended into the lung
      parenchyma. EBUS-guided FNA was performed to obtain diagnostic materials. The
      ROSE of cytology specimen revealed numerous tight clusters of cells with well
      defined, but scant cytoplasm. These cells were relatively small and bland with
      high N/C ratio, resembling benign ductal cells. Neither cilia nor intranuclear
      inclusions were noted. Focal extracellular metachromatic mucinous materials were
      also noted. A preliminary diagnosis of "low-grade epithelial neoplasm, favor low
      grade MEC" was rendered. The definitive diagnosis was confirmed by both cytology
      and core biopsy. EBUS-guided FNA cytology can be a reliable method for the
      diagnosis of bronchial low grade MEC. The cyto-morphology of ROSE can indicate
      the diagnosis of low grade MEC and direct the appropriate follow-up triage of the
      specimen.

PMID- 23008144
TI  - Efficacy of the retreatment of hepatitis C virus infections after liver
      transplantation: role of an aggressive approach.
AB  - A sustained virological response (SVR) is achieved by 30% of naive liver
      transplantation (LT) recipients treated with pegylated interferon (PEG-IFN) and
      ribavirin (RBV). Almost no data are available about retreatment. The aim of this
      study was to assess the efficacy, tolerability, and SVR predictors of
      retreatment. Data were collected from 4 centers on the retreatment of prior
      nonresponders to standard therapy or PEG-IFN (with or without RBV) and relapsers.
      Seventy-nine of 301 treatment-experienced LT patients (26%), who had a median age
      of 59 years (range = 35-77 years) and were mostly male (72%) and infected with
      genotype 1 (87%), were retreated with PEG-IFN and RBV at a median of 6.9 years
      after LT. During the first course of therapy, 35% were treated with interferon,
      49% received tacrolimus, 52% received steroids, and 49.5% were relapsers.
      Retreatment was started at a median of 1.9 years (range = 45 days to 8.2 years)
      after the end of the first course. The proportion of patients with cirrhosis
      increased from 10% to 37% (P < 0.001). In addition, in retreated patients, full
      initial RBV doses (P = 0.03), growth factors [erythropoietin (P < 0.001) and
      granulocyte colony-stimulating factor (P = 0.048)], and transfusions (P = 0.03)
      were used more frequently, and the treatment duration was longer (P = 0.03). An
      end-of-treatment response was achieved in 61%, whereas SVR, which was associated
      with improved survival, occurred in 28 (35%). The variables predicting SVR were
      age (P = 0.04), disease severity [fibrosis (50% with F0-F2 versus 26% with F3-4),
      P = 0.03; bilirubin, P = 0.006; platelet count, P = 0.03], adherence, and viral
      kinetics. None of the patients without an early virological response achieved
      SVR. There was a trend of prior relapsers achieving higher SVR rates than prior
      nonresponders. In conclusion, SVR, which was achieved by approximately one-third
      of the retreated patients, can be predicted with the same variables used for
      naive LT recipients (age, disease severity, adherence, and viral kinetics) and is
      associated with enhanced survival.

PMID- 23008145
TI  - Accelerated diffusion spectrum imaging with compressed sensing using adaptive
      dictionaries.
AB  - Diffusion spectrum imaging offers detailed information on complex distributions
      of intravoxel fiber orientations at the expense of extremely long imaging times
      (~1 h). Recent work by Menzel et al. demonstrated successful recovery of
      diffusion probability density functions from sub-Nyquist sampled q-space by
      imposing sparsity constraints on the probability density functions under wavelet
      and total variation transforms. As the performance of compressed sensing
      reconstruction depends strongly on the level of sparsity in the selected
      transform space, a dictionary specifically tailored for diffusion probability
      density functions can yield higher fidelity results. To our knowledge, this work
      is the first application of adaptive dictionaries in diffusion spectrum imaging,
      whereby we reduce the scan time of whole brain diffusion spectrum imaging
      acquisition from 50 to 17 min while retaining high image quality. In vivo
      experiments were conducted with the 3T Connectome MRI. The root-mean-square error
      of the reconstructed "missing" diffusion images were calculated by comparing them
      to a gold standard dataset (obtained from acquiring 10 averages of diffusion
      images in these missing directions). The root-mean-square error from the proposed
      reconstruction method is up to two times lower than that of Menzel et al.'s
      method and is actually comparable to that of the fully-sampled 50 minute scan.
      Comparison of tractography solutions in 18 major white-matter pathways also
      indicated good agreement between the fully-sampled and 3-fold accelerated
      reconstructions. Further, we demonstrate that a dictionary trained using
      probability density functions from a single slice of a particular subject
      generalizes well to other slices from the same subject, as well as to slices from
      other subjects.

PMID- 23008146
TI  - Hypercrosslinked aromatic heterocyclic microporous polymers: a new class of
      highly selective CO2 capturing materials.
AB  - Aromatic heterocyclic microporous polymers with high surface areas are obtained
      by directly crosslinking of the heterocyclic monomers under mild conditions.
      Owing to the narrow pore system and the heteroatom-rich pore surface, these
      networks exhibit high CO(2) adsorption capacity and selectivity. At 273 K, the
      CO(2)/N(2) selectivity of Py-1 is about 117, which is among the highest the
      reported microporous materials.

PMID- 23008147
TI  - When the Cell Stress Society International became South American: meeting report
      of the IX International Workshop on the Molecular Biology of Stress Responses.
AB  - The International Workshop on the Molecular Biology of the Stress Response
      organized by the Cell Stress Society International was held in Porto Alegre,
      Brazil, on May 27-30, 2012, as part of the development of the Latin American
      Chapter of the Society, a superb initiative headed by Drs. Antonio De Maio and
      Larry Hightower. The meeting took place in the wonderful facilities of the
      Pontificia Universidade do Rio Grande do Sul (PUCRS) and was warmly chaired by
      Professor Cristina Bonorino. Thirty-four invited speakers presented their work to
      more than 200 scientists and, even more importantly, to 150 registered students,
      who were the main beneficiaries of the meeting. The first day of the workshop was
      dedicated to an educational program for students, young investigators, and
      participants who were unfamiliar with the field of molecular chaperones and the
      stress response. Speakers in this pre-workshop were Dr. Harm Kampinga, Dr. Lea
      Sistonen, Dr. Larry Hightower, Dr. Ivor Benjamin, Dr. Daniel Ciocca, and Dr.
      Linda Hendershot. Then, the scientific sessions discussed below followed.

PMID- 23008149
TI  - Cytologic features of fibrolamellar carcinoma with mucin production: a rare
      variant of combined hepatocellular-cholangiocarcinoma.
AB  - Fibrolamellar carcinoma (FC) is an uncommon tumor that usually arises in non
      cirrhotic livers of adolescents or young adults. It differs clinically from
      hepatocellular carcinoma in its better prognosis and lack of gender predilection.
      Cytologically, the tumor is composed of large polygonal cells with abundant
      cytoplasm, pleomorphic nuclei, and prominent large nucleoli. A variant of FC with
      mucinous differentiation has been previously described. These tumors have been
      regarded as combined hepatocellular cholangiocarcinomas. Herein, we report the
      case of a 44-year-old Asian female with a large liver mass present for
      approximately two years. Core needle biopsy with imprint cytology demonstrated FC
      with areas of intracellular mucin. To our knowledge, cytological features of this
      rare tumor have not been described before.

PMID- 23008151
TI  - Diffusion weighted vertical gradient and spin echo.
AB  - In this work, diffusion weighting and parallel imaging is combined with a
      vertical gradient and spin echo data readout. This sequence was implemented and
      evaluated on healthy volunteers using a 1.5 and a 3 T whole-body MR system. As
      the vertical gradient and spin echo trajectory enables a higher k-space velocity
      in the phase-encoding direction than single-shot echo planar imaging, the
      geometrical distortions are reduced. When combined with parallel imaging such as
      generalized autocalibrating partially parallel acquisition, the geometric
      distortions are reduced even further, while also keeping the minimum echo time
      reasonably low. However, this combination of a diffusion preparation and multiple
      refocusing pulses during the vertical gradient and spin echo readout, generally
      violates the Carr-Purcell-Meiboom-Gill condition, which leads to interferences
      between echo pathways. To suppress the stimulated echo pathway, refocusing pulses
      with a sharper slice profiles and an odd/even crusher variation scheme were
      implemented and evaluated. Being a single-shot acquisition technique, the
      reconstructed images are robust to rigid-body head motion and spatially varying
      brain motion, both of which are common sources of artifacts in diffusion MRI.

PMID- 23008152
TI  - All-solution-processed flexible thin film piezoelectric nanogenerator.
AB  - An all-solution-processed flexible thin film piezoelectric nanogenerator is
      demonstrated using reactive zinc hydroxo-condensation and a screen-printing
      method. The highly elastic thin film allows the piezoelectric energy to be
      generated through the mechanical rolling and muscle stretching of the
      piezoelectric unit. This flexible all solution-processed nanogenerator is
      promising for use in future energy harvesters such as wearable human patches and
      mobile electronics.

PMID- 23008150
TI  - Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the
      cleft lip with or without cleft palate locus identified by genome-wide
      association on chromosome 1p22.
AB  - BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a
      common birth defect with complex etiology reflecting the action of multiple
      genetic and environmental factors. Genome-wide association studies have
      successfully identified five novel loci associated with NSCL/P, including a locus
      on 1p22.1 near the ABCA4 gene. Because neither expression analysis nor mutation
      screening support a role for ABCA4 in NSCL/P, we investigated the adjacent gene
      ARHGAP29. METHODS: Mutation screening for ARHGAP29 protein coding exons was
      conducted in 180 individuals with NSCL/P and controls from the United States and
      the Philippines. Nine exons with variants in ARHGAP29 were then screened in an
      independent set of 872 cases and 802 controls. Arhgap29 expression was evaluated
      using in situ hybridization in murine embryos. RESULTS: Sequencing of ARHGAP29
      revealed eight potentially deleterious variants in cases including a frameshift
      and a nonsense variant. Arhgap29 showed craniofacial expression and was reduced
      in a mouse deficient for Irf6, a gene previously shown to have a critical role in
      craniofacial development. CONCLUSION: The combination of genome-wide association,
      rare coding sequence variants, craniofacial specific expression, and interactions
      with IRF6 support a role for ARHGAP29 in NSCL/P and as the etiologic gene at the
      1p22 genome-wide association study locus for NSCL/P. This work suggests a novel
      pathway in which the IRF6 gene regulatory network interacts with the Rho pathway
      via ARHGAP29. Birth Defects Research (Part A) 2012. (c) 2012 Wiley Periodicals,
      Inc.

PMID- 23008153
TI  - Gene transfer therapy by either type 1 or type 2 adeno-associated virus
      expressing human prostaglandin I2 synthase gene is effective for treatment of
      pulmonary arterial hypertension.
AB  - Prostaglandin I(2) (PGI(2)) plays an important role in the clinical treatment of
      pulmonary arterial hypertension (PAH). However, the administration of PGI(2)
      involves continuous intravenous infusion using an indwelling catheter, which
      limits the patient's quality of life and increases the risk of infection. We
      therefore investigated whether human PGI(2) synthase (hPGIS) gene transfer using
      an adeno-associated virus (AAV) vector is still effective in a mouse model of PAH
      and tested for differences in the therapeutic efficacy of PAH among AAV
      serotypes. The PAH was induced by subjecting mice to hypoxia (10% O(2)). Type 1
      AAV expressing hPGIS (AAV1-hPGIS) or type 2 AAV expressing hPGIS (AAV2-hPGIS) was
      injected into the thigh muscle of mice. Both vectors expressing hPGIS produced
      strong hPGIS protein expression in the mouse thigh skeletal muscles after 8 weeks
      of hypoxia. The administration of AAV1-hPGIS or AAV2-hPGIS also significantly
      inhibited the hypoxia-induced increase in right ventricular systolic pressure,
      the ratio of right ventricular weight to body weight (RV/BW), and the ratio of RV
      weight to left ventricular plus septal weight (RV/LV + S), and significantly
      attenuated the hypoxia-induced increase in medial wall thickness of peripheral
      pulmonary arteries. Furthermore, there were no significant differences in the
      degree of amelioration in RV systolic pressure, RV/BW, RV/LV + S, and percentage
      of wall thickness of peripheral pulmonary arteries between AAV1-hPGIS and AAV2
      hPGIS administrations. In conclusion, we revealed that type 1 and type 2 AAV are
      equally effective for the treatment of PAH in a hypoxia-induced mouse model. Gene
      transfer therapy using AAV expressing hPGIS is, therefore, a potential
      therapeutic breakthrough for PAH.

PMID- 23008154
TI  - Upregulation of beta3-adrenergic receptor expression in the atrium of rats with
      chronic heart failure.
AB  - OBJECTIVES: To investigate the expression of beta(3)-adrenergic receptor (beta(3)
      AR) in the atrium of rats with chronic heart failure (CHF). METHODS: The heart
      failure rat model was established by aortic constriction. Thirty-six male Wistar
      rats were divided into Sham group (n = 10) and heart failure model group (n =
      26), which were further divided into CHF control (CHF group) and BRL group. The
      rats in the BRL group were treated with a selective beta(3)-AR agonist, BRL-37344
      (4.0 nmol/kg, twice weekly) for 4 weeks. RESULTS: In the BRL group, the left
      ventricular end-systolic pressure (83.21 +/- 13.0 vs 101.50 +/- 12.12 mm Hg) and
      the absolute values of the maximal rate of rise and fall of left ventricular
      pressure ([+/-dP/dtmax] 2.81 +/- 0.04 vs 0.35 +/- 0.04 and -2.72 +/- 0.06 vs 
      3.33 +/- 0.06) were lower than in the CHF group (P < .01). The left atrial mass
      index (LAMI) in the BRL group (0.4132 +/- 0.0306) was higher than that in the CHF
      (0.3212 +/- 0.0136) or Sham group (0.2683 +/- 0.0145; P < .01). The levels of the
      left atrial beta(3)-AR messenger RNA (mRNA) expression in the BRL group (0.932 +/
      0.055) was higher than that in the CHF (0.706 +/- 0.043) or Sham group (0.310 +/
      0.020; P < .01). In all animals, there was a positive correlation between the
      level of beta(3)-AR mRNA expression and the left or right atrial mass index
      (correlation coefficient ranged from 0.744 to 0.937). CONCLUSION: There is a
      significant increase in the beta(3)-AR mRNA expression in the atrium of rats with
      heart failure. The level of beta(3)-AR mRNA expression was associated with the
      AMI and was enhanced by a selective beta(3)-AR agonist, BRL-37344.

PMID- 23008155
TI  - White-rot fungi capable of decolourising textile dyes under alkaline conditions.
AB  - Twelve white-rot fungal strains belonging to seven different species were
      screened on plates under alkaline condition to study the decolourisation of the
      textile dyes Reactive Black 5 and Poly R-478. Three strains of Trametes
      versicolor (Micoteca da Universidade do Minho (MUM) 94.04, 04.100 and 04.101) and
      one strain of Phanerochaete chrysosporium (MUM 94.15) showed better
      decolourisation results. These four strains were used for decolourisation studies
      in liquid culture medium. All four selected strains presented more efficient
      decolourisation rates on Reactive Black 5 than on Poly R-478. For both dyes on
      solid and liquid culture media, the decolourisation capability exhibited by these
      strains depended on dye concentration and pH values of the media. Finally, the
      decolourisation of Reactive Black 5 by T. versicolor strains MUM 94.04 and 04.100
      reached 100 %. In addition, the highest white-rot fungi ligninolytic enzyme
      activities were found for these two strains.

PMID- 23008156
TI  - Functional connectivity between parietal and frontal brain regions and
      intelligence in young children: the Generation R study.
AB  - It has been shown in adults that individual differences in intelligence are
      related to the integrity of the interaction between parietal and frontal brain
      regions. Since connectivity between distant brain regions strengthens during
      childhood, it is unclear when in the course of development this relationship
      emerges. Thus, the goal of this study was to determine whether parietal-frontal
      functional connectivity is associated with intelligence in young children. We
      performed independent component analyses on resting-state fMRI data of 115
      children (6-8 years old) to select seed and target regions for a seed/target
      region correlation analysis. We found that higher nonverbal intelligence was
      associated with increased functional connectivity between right parietal and
      right frontal regions, and between right parietal and dorsal anterior cingulate
      regions. The association between intelligence and functional connectivity between
      certain brain regions was stronger in girls than boys. In conclusion, we found
      that connectivity between the parietal and frontal lobes is critically involved
      in intelligence in young children.

PMID- 23008157
TI  - Aortocoronary saphenous vein graft rupture during diagnostic angiography.
AB  - Coronary saphenous vein graft (SVG) rupture during diagnostic angiography is a
      very rare but known complication of the procedure. It has typically been reported
      to occur at the site of pseudoaneurysms or secondary to an interventional
      procedure involving the graft. We present a case of SVG mid-body rupture during
      diagnostic angiography that occurred without evidence of pseudoaneurysmal
      changes.

PMID- 23008158
TI  - A simple method for the determination of the partitioning of nitroxide probes in
      microheterogeneous media.
AB  - The use of the ESR g-factor of spin labels for the easy and clean assessment of
      their partitioning in microheterogeneous media is described. The method
      constitutes a valuable alternative in those cases where the classical Benesi
      Hildebrand treatment, based on UV-visible measurements, is difficult or not
      feasible.

PMID- 23008159
TI  - Functionalized CdSe/ZnS QDs for the detection of nitroaromatic or RDX explosives.
AB  - Chemically modified CdSe/ZnS quantum dots (QDs) are used as fluorescent probes
      for the analysis of explosives, and specifically, the detection of
      trinitrotoluene (TNT) or trinitrotriazine (RDX). The QDs are functionalized with
      electron-donating ligands that bind nitro-containing explosives, exhibiting
      electron-acceptor properties, to the QD surface, via supramolecular donor
      acceptor interactions leading to the quenching of the luminescence of the QDs.

PMID- 23008160
TI  - Effects of individual alpha rTMS applied to the auditory cortex and its
      implications for the treatment of chronic tinnitus.
AB  - An increasing amount of studies apply repetetive transcranial magnetic
      stimulation (rTMS) to treat chronic tinnitus, yet the neurophysiological impacts
      have remained largely obscure. Several studies show that endogenous brain rhythms
      may be enhanced via diverse brain stimulation techniques applying rhythmic
      stimulation. Here, we investigated in normal hearing participants whether
      application of rTMS (left auditory cortex) with an individualized alpha frequency
      was capable of increasing alpha activity in stimulated auditory regions in a
      sustained manner. Behavioral intensity discrimination performance worsened for
      the rTMS group as compared to Sham. Electroencephalography (EEG) data, however,
      clearly show that this functional inhibition is not accompanied by increases of
      auditory cortical alpha. Even though more pronounced power reductions for the
      rTMS group were observed at slower frequencies (delta to theta range) at
      stimulated and other sites of the left hemisphere, they were unrelated to
      behavioral changes. Our results also strongly suggest that the amount of power
      modulations at these slower frequencies is strongly dependent on pre-rTMS power,
      thus supporting current state-dependency notions. Strong relationships to
      behavioral changes were in particular observed for anterior cingulate cortex
      (ACC) beta power and posterior cingulate cortex (PCC) beta connectivity.
      Moreover, these beta band measures were strongly inter-related and when viewed
      together specifically sensitive to behavioral changes in the rTMS group. We
      conclude that currently alpha frequency rTMS is not a promising avenue for the
      treatment of chronic tinnitus and that beneficial effects could be mediated via
      nonauditory systems. Our study argues for the value of combined EEG-TMS studies
      when investigating the impacts of rTMS.

PMID- 23008161
TI  - A stability analysis of a modified version of the chi-square ratio statistic:
      implications for equivalence testing of aerodynamic particle size distribution.
AB  - Demonstration of equivalence in aerodynamic particle size distribution (APSD;
      e.g., by comparing cascade impactor (CI) profiles) constitutes one of key in
      vitro tests for supporting bioequivalence between test (T) and reference (R)
      orally inhaled drug products (OIDPs). A chi-square ratio statistic (CSRS) was
      previously proposed for equivalence testing of CI profiles. However, it was
      reported that the CSRS could not consistently discriminate between equivalent and
      inequivalent CI profiles. The objective of the overall project was to develop a
      robust and sensitive methodology for assessing equivalence of APSD profiles of T
      and R OIDPs. We propose here a modified version of the CSRS (mCSRS) and evaluated
      systematically its behavior when T and R CI profiles were identical. Different
      scenarios comprising CI profiles with different number of deposition sites and
      shapes were generated by Monte-Carlo simulation. For each scenario, the mCSRS was
      applied to 20,000 independent sets of 30 T and 30 R CI profiles that were
      identical. Different metrics (including mean and median) of the distribution of
      900 mCSRSs (30 T * 30 R) were then evaluated for their suitability as a test
      statistic (i.e., independent of the number of sites and shape of the CI profile)
      for APSD equivalence testing. The median of the distribution of 900 mCSRSs
      (MmCSRS) was one regardless of the number of sites and shape of the CI profile.
      Hence, the MmCSRS is a robust metric for CI profile equivalence testing when T
      and R CI profiles are identical and potentially useful for APSD equivalence
      testing.

PMID- 23008162
TI  - Transulnar catheterization in patients with ipsilateral radial artery occlusion.
AB  - BACKGROUND: The transradial approach to percutaneous coronary intervention (PCI)
      has recently gained popularity among interventionalists. However, radial artery
      occlusion (RAO) limits the ability for repeat catheterization. In current
      practice, transulnar catheterization is thought to be a contraindication in
      patients with ipsilateral RAO. METHODS: Seventeen consecutive patients undergoing
      transulnar catheterization and PCI were reviewed. Each of the patients had
      clinical follow-up post-procedure at days 1, 7, and 30. RESULTS: We successfully
      performed 17 ulnar catheterizations in patients with ipsilateral RAO. All patents
      were subsequently found to have adequate collaterals from the anterior
      interosseous branch. One patient developed ulnar artery spasm and another patient
      developed a forearm hematoma. Overall, no patient suffered any ulnar nerve
      injury. The ulnar artery was patent both by palpation and by the presence of an
      adequate plethysmographic signal during follow-up at days 1, 7, and 30. No
      patients developed with any signs or symptoms of hand ischemia during follow-up.
      CONCLUSION: In patients with RAO, ipsilateral transulnar catheterization may not
      be an absolute contraindication. Our results suggest that extensive collaterals
      from the anterior interosseous artery may be the reason for protection against
      hand ischemia in the setting of RAO.

PMID- 23008163
TI  - High protein adsorptive capacity of amino acid-functionalized hydroxyapatite.
AB  - Charged functional groups present on the surface of biomaterials play an
      important role to regulate the affinity and attachment of macromolecules,
      including proteins, on the surface of biomaterials. In this study, the protein
      adsorptive capacity of hydroxyapatite (HA) was regulated by introducing different
      amino acids during the precipitation of HA. After incubation of HA samples in
      5000 MUg/mL lysozyme solution at pH 7.4 for 24 h, unmodified HA adsorbed 0.886
      mg/m(2) of lysozyme while amino acid-functionalized HA (AA-HA) particles
      demonstrated higher adsorption capacity ranging from 1.090 to 1.680 mg/m(2).
      Incorporation of amino acids with longer side chain lengths decreased the
      crystallinity and increased the negative value of the surface charge of HA
      particles. The specific surface areas were significantly increased in the
      presence of amino acids. Protein loading capacity onto AA-HA was further enhanced
      by regulating the pH of working solution whereby the protein adsorption rate
      increased with decreasing the pH, while reverse trend obtained in unmodified HA.
      The study demonstrated that the amount of adsorbed lysozyme onto AA-HA particles
      was correlated with the particles' surface charges.

PMID- 23008164
TI  - Living on the edge with too many mouths to feed: why dopamine neurons die.
AB  - Although genes, protein aggregates, environmental toxins, and other factors
      associated with Parkinson's disease (PD) are widely distributed in the nervous
      system and affect many classes of neurons, a consistent feature of PD is the
      exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What
      is it about these neurons, among all other neurons in the brain, that makes them
      so susceptible in PD? We hypothesize that a major contributory factor is the
      unique cellular architecture of SNc DA neuron axons. Their large, complex axonal
      arbour puts them under such a tight energy budget that it makes them particularly
      susceptible to factors that contribute to cell death, including unique molecular
      characteristics associated with SNc DA neurons and nonspecific, nervous-system
      wide factors.

PMID- 23008167
TI  - The use of PTCA in acute mitral regurgitation and cardiogenic shock: revisited
      with impella.

PMID- 23008165
TI  - Cross-sectional and longitudinal association of body mass index and brain volume.
AB  - Although a link between body mass index (BMI) and brain volume has been
      established in several cross-sectional studies, evidence of the association
      between change in BMI over time and changes in brain structure is limited. Using
      data from a cohort of 347 former lead workers and community controls with two
      magnetic resonance imaging scans over a period of ~5 years, we estimated cross
      sectional and longitudinal associations of BMI and brain volume using both region
      of interest (ROI) and voxel-based morphometric (VBM) methods. We found that
      associations of BMI and brain volume were not significantly different in former
      lead workers when compared with community controls. In the cross-sectional
      analysis, higher BMIs were associated with smaller brain volumes in gray matter
      (GM) using both ROI and VBM approaches. No associations with white matter (WM)
      were observed. In the longitudinal analysis, higher baseline BMI was associated
      with greater decline in temporal and occipital GM ROI volumes. Change in BMI over
      the 5-year period was only associated with change in hippocampal volume and was
      not associated with change in any of the GM ROIs. Overall, higher BMI was
      associated with lower GM volume in several ROIs and with declines in volume in
      temporal and occipital GM over time. These results suggest that sustained high
      body mass may contribute to progressive temporal and occipital atrophy.

PMID- 23008169
TI  - Brain activation pattern related to gait disturbances in Parkinson's disease.
AB  - Gait disturbances represent a therapeutic challenge in Parkinson's disease (PD).
      To further investigate their underlying pathophysiological mechanisms, we
      compared brain activation related to mental imagery of gait between 15 PD
      patients and 15 age-matched controls using a block-design functional MRI
      experiment. On average, patients showed altered locomotion relatively to
      controls, as assessed with a standardized gait test that evaluated the severity
      of PD-related gait disturbances on a 25-m path. The experiment was conducted in
      the subjects as they rehearsed themselves walking on the same path with a gait
      pattern similar as that during locomotor evaluation. Imagined walking times were
      measured on a trial-by-trial basis as a control of behavioral performance. In
      both groups, mean imagined walking time was not significantly different from that
      measured during real gait on the path used for evaluation. The between-group
      comparison of the mental gait activation pattern with reference to mental imagery
      of standing showed hypoactivations within parieto-occipital regions, along with
      the left hippocampus, midline/lateral cerebellum, and presumed pedunculopontine
      nucleus/mesencephalic locomotor area, in patients. More specifically, the
      activation level of the right posterior parietal cortex located within the
      impaired gait-related cognitive network decreased proportionally with the
      severity of gait disturbances scored on the path used for gait evaluation and
      mental imagery. These novel findings suggest that the right posterior parietal
      cortex dysfunction is strongly related to the severity of gait disturbances in
      PD. This region may represent a target for the development of therapeutic
      interventions for PD-related gait disturbances.

PMID- 23008168
TI  - A statistical algorithm for assessing cellular alignment.
AB  - Current statistical techniques for analyzing cellular alignment data in the
      fields of biomaterials and tissue engineering are limited because of heuristic
      and less quantitative approaches. For example, generally a cutoff degree limit
      (commonly 20 degrees) is arbitrarily defined within which cells are considered
      "aligned." The effectiveness of a patterned biomaterial in guiding the alignment
      of cells, such as neurons, is often critical to predict relationships between the
      biomaterial design and biological outcomes, both in vitro and in vivo. This
      becomes particularly important in the case of peripheral neurons, which require
      precise axon guidance to obtain successful regenerative outcomes. To address this
      issue, we have developed a protocol for processing cellular alignment data sets,
      which implicitly determines an "angle of alignment." This was accomplished as
      follows: cells "aligning" with an underlying, anisotropic scaffold display
      uniformly distributed angles up to a cutoff point determined by how effective the
      biomaterial is in aligning cells. Therefore, this fact was then used to determine
      where an alignment angle data set diverges from a uniform distribution. This was
      accomplished by measuring the spacing between the collected, increasingly ordered
      angles and analyzing their underlying distributions using a normalized cumulative
      periodogram criterion. The proposed protocol offers a novel way to implicitly
      define cellular alignment, with respect to various anisotropic biomaterials. This
      method may also offer an alternative to assess cellular alignment, which could
      offer improved predictive measures related to biological outcomes. Furthermore,
      the approach described can be used for a broad range of cell types grown on 2D
      surfaces, but would not be applicable to 3D scaffold systems in the present
      format.

PMID- 23008170
TI  - Key functional circuitry altered in schizophrenia involves parietal regions
      associated with sense of self.
AB  - There is still no clear consensus as to which of the many functional and
      structural changes in the brain in schizophrenia are of most importance, although
      the main focus to date has been on those in the frontal and cingulate cortices.
      In the present study, we have used a novel holistic approach to identify brain
      wide functional connectivity changes in medicated schizophrenia patients, and
      functional connectivity changes were analyzed using resting-state fMRI data from
      69 medicated schizophrenia patients and 62 healthy controls. As far as we are
      aware, this is the largest population reported in the literature for a resting
      state study. Voxel-based morphometry was also used to investigate gray and white
      matter volume changes. Changes were correlated with illness duration/symptom
      severity and a support vector machine analysis assessed predictive validity. A
      network involving the inferior parietal lobule, superior parietal gyrus,
      precuneus, superior marginal, and angular gyri was by far the most affected (68%
      predictive validity compared with 82% using all connections) and different
      components correlated with illness duration and positive and negative symptom
      severity. Smaller changes occurred in emotional memory and sensory and motor
      processing networks along with weakened interhemispheric connections. Our
      findings identify the key functional circuitry altered in schizophrenia involving
      the default network midline cortical system and the cortical mirror neuron
      system, both playing important roles in sensory and cognitive processing and
      particularly self-processing, all of which are affected in this disorder.
      Interestingly, the functional connectivity changes with the strongest links to
      schizophrenia involved parietal rather than frontal regions.

PMID- 23008171
TI  - Studies related to Norway spruce galactoglucomannans: chemical synthesis,
      conformation analysis, NMR spectroscopic characterization, and molecular
      recognition of model compounds.
AB  - Galactoglucomannan (GGM) is a polysaccharide mainly consisting of mannose,
      glucose, and galactose. GGM is the most abundant hemicellulose in the Norway
      spruce (Picea abies), but is also found in the cell wall of flax seeds, tobacco
      plants, and kiwifruit. Although several applications for GGM polysaccharides have
      been developed in pulp and paper manufacturing and the food and medical
      industries, attempts to synthesize and study distinct fragments of this
      polysaccharide have not been reported previously. Herein, the synthesis of one of
      the core trisaccharide units of GGM together with a less-abundant tetrasaccharide
      fragment is described. In addition, detailed NMR spectroscopic characterization
      of the model compounds, comparison of the spectral data with natural GGM,
      investigation of the acetyl-group migration phenomena that takes place in the
      polysaccharide by using small model compounds, and a binding study between the
      tetrasaccharide model fragment and a galactose-binding protein (the toxin
      viscumin) are reported.

PMID- 23008172
TI  - Rebuttal: the use of PTCA in acute mitral regurgitation and cardiogenic shock:
      revisited with impella-response from the authors.

PMID- 23008173
TI  - Preparation and characterization of collagen-nanohydroxyapatite biocomposite
      scaffolds by cryogelation method for bone tissue engineering applications.
AB  - Recent efforts of bone repair focus on development of porous scaffolds for cell
      adhesion and proliferation. Collagen-nanohydroxyapatite (HA) scaffolds (70:30;
      50:50; and 30:70 mass percentage) were produced by cryogelation technique using 1
      ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide
      as crosslinking agents. A pure collagen scaffold was used as control. Morphology
      analysis revealed that all cryogels had highly porous structure with
      interconnective porosity and the nanoHA aggregates were randomly dispersed
      throughout the scaffold structure. Chemical analysis showed the presence of all
      major peaks related to collagen and HA in the biocomposites and indicated
      possible interaction between nanoHA aggregates and collagen molecules. Porosity
      analysis revealed an enhancement in the surface area as the nanoHA percentage
      increased in the collagen structure. The biocomposites showed improved mechanical
      properties as the nanoHA content increased in the scaffold. As expected, the
      swelling capacity decreased with the increase of nanoHA content. In vitro studies
      with osteoblasts cells showed that they were able to attach and spread in all
      cryogels surfaces. The presence of collagen-nanoHA biocomposites resulted in
      higher overall cellular proliferation compared to pure collagen scaffold. A
      statistically significant difference between collagen and collagen-nanoHA
      cryogels was observed after 21 day of cell culture. These innovative collagen
      nanoHA cryogels could have potentially appealing application as scaffolds for
      bone regeneration.

PMID- 23008174
TI  - Huntington's disease: how intermediate are intermediate repeat lengths?
AB  - BACKGROUND: Huntington's disease (HD) is a devastating heredoneurodegenerative
      disorder associated with a wide variety of neurological and psychiatric symptoms
      caused by an expanded CAG repeat in the HTT gene. The expansion mutation in HTT
      is dominantly transmitted and codes for a protein named huntingtin (htt).
      HYPOTHESIS: One hypothesis, according to a multistep mechanism, is that the
      intergenerational transmission of the normal repeat size causes small,
      progressive CAG stretch elongations in the general population from one generation
      to another, until a critical pathological CAG repeat threshold is reached.
      Mutations may originate in the offspring from paternally transmitted CAG repeats,
      falling within an intermediate alleles (IA) range of 27 to 35 in repeat length.
      CONCLUSIONS: There has been emerging evidence that some individuals with IAs
      might develop an HD phenotype. This presents a challenge for genetic counseling,
      because these individuals are often reassured that they are "disease free."
      However, there are many unanswered questions related to the role of IAs in the
      development of the HD phenotype and in the pathogenesis of HD.

PMID- 23008175
TI  - The (Eigen)value of diffusion tensor imaging to investigate depression after
      traumatic brain injury.
AB  - BACKGROUND: Many people with a traumatic brain injury (TBI), even mild to
      moderate, will develop major depression (MD). Recent studies of patients with MD
      suggest reduced fractional anisotropy (FA) in dorsolateral prefrontal cortex
      (DLPFC), temporal lobe tracts, midline, and capsule regions. Some of these
      pathways have also been found to have reduced FA in patients with TBI. It is
      unknown whether the pathways implicated in MD after TBI are similar to those with
      MD without TBI. This study sought to investigate whether there were specific
      pathways unique to TBI patients who develop MD. METHODS: A sample of TBI-MD
      subjects (N = 14), TBI-no-MD subjects (N = 12), MD-no-TBI (N = 26), and control
      subjects (no TBI or MD, N = 23), using a strict measurement protocol underwent
      psychiatric assessments and diffusion tensor brain Magnetic Resonance Imaging
      (MRI). RESULTS: The findings of this study indicate that (1) TBI patients who
      develop MD have reduced axial diffusivity in DLPFC, corpus callosum (CC), and
      nucleus accumbens white matter tracts compared to TBI patients who do not develop
      MD and (2) MD patients without a history of TBI have reduced FA along the CC. We
      also found that more severe MD relates to altered radial diffusivity.
      CONCLUSIONS: These findings suggest that compromise to specific white matter
      pathways, including both axonal and myelination aspects, after a mild TBI
      underlie the susceptibility of these patients developing MD.

PMID- 23008176
TI  - Poly(9,9'-diheylfluorene carbazole) functionalized with reduced graphene oxide:
      convenient synthesis using nitrogen-based nucleophiles and potential applications
      in optical limiting.
AB  - Covalently functionalized reduced graphene oxide (RGO) sheet was prepared by
      treating nitrogen-centered anions generated from poly(9,9'-diheylfluorene
      carbazole) (PCF) with GO. The resultant hybrids with different chemical behavior
      were separated by centrifugation. The covalent modification was fully
      characterized by IR spectroscopy, UV/Vis spectroscopy, thermogravimetric analysis
      (TGA), Raman spectroscopy, TEM, and SEM. It was found that RGO-PCF-s, the soluble
      part, was split into small platelets with a size of about 200 nm, and the
      hydrophobic polymer PCF became hydrophilic after wrapping by RGO. The content of
      RGO in RGO-PCF-s was about 11.9%, and the hybrid material showed good dispersion
      stability in water. Besides, RGO-PCF-i, the insoluble part, with larger size,
      displayed excellent optical-limiting response, in which both nonlinear absorption
      and nonlinear scattering play important roles. As nitrogen-centered anions are an
      important type of intermediates in chemistry, this one-step "grafting-to"
      strategy could be used to obtain RGO-based materials with different applications.

PMID- 23008177
TI  - Rationale and design of the MGuard for acute ST elevation reperfusion MASTER
      trial.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) improves survival
      compared with thrombolytic therapy in ST-segment elevation myocardial infarction
      (STEMI), with much of the benefit attributable to greater rates of normal
      epicardial and myocardial perfusion resulting in enhanced myocardial salvage.
      However, reduced tissue reperfusion after primary PCI may occur from distal
      thromboemboli with capillary plugging. The MGuard stent consists of a balloon
      expandable metallic scaffold with mesh sleeve fibers of polyethylene
      terephthalate attached to its outer surface to trap friable debris/thrombi and
      reduce distal embolization. The MGuard for Acute ST Elevation Reperfusion
      (MASTER) trial has been designed to evaluate the MGuard stent in patients with
      STEMI. STUDY DESIGN: The MASTER trial is a prospective, multicenter, randomized
      study designed to compare the incidence of complete (=70%) ST-segment resolution
      with PCI using bare metal or drug-eluting stents (the control arm) versus PCI
      with the MGuard stent, measured 60 to 90 min after the last angiogram (primary
      endpoint). Secondary endpoints include the rates of TIMI flow and myocardial
      blush, and clinical outcomes through 1-year follow-up. The study has enrolled 432
      patients with STEMI undergoing primary or rescue angioplasty within 12 hr of
      symptom onset and includes substudies with cardiac magnetic resonance imaging and
      quantitative coronary angiography to evaluate infarct size, microvascular
      obstruction, and angiographic restenosis. CONCLUSIONS: Distal embolization is
      common during primary PCI and results in reduced myocardial perfusion and lack of
      reduction of infarct size. The MASTER trial is a prospective, randomized trial
      designed to assess the potential of the novel MGuard stent with protective mesh
      net to reduce embolization and enhance myocardial reperfusion compared with
      routine PCI in the setting of STEMI.

PMID- 23008178
TI  - Novel injectable biomimetic hydrogels with carbon nanofibers and self assembled
      rosette nanotubes for myocardial applications.
AB  - The objective of the present in vitro study was to investigate cardiomyocyte
      functions, specifically their adhesion and proliferation, on injectable scaffolds
      containing RNT (rosette nanotubes) and CNF (carbon nanofibers) in a pHEMA (poly(2
      hydroxyethyl methacrylate)) hydrogel to determine their potential for myocardial
      tissue engineering applications. RNTs are novel biocompatible nanomaterials
      assembled from synthetic analogs of DNA bases guanine and cytosine that self
      assemble within minutes when placed in aqueous solutions at body temperatures.
      These materials could potentially improve cardiomyocyte functions and
      solidification time of pHEMA and CNF composites. Because heart tissue is
      conductive, CNFs were added to pHEMA to increase the composite's conductivity.
      Our results showed that cardiomyocyte density increased after 4 h, 1 day, and 3
      days with greater amounts of CNFs and greater amounts of RNTs in pHEMA (up to 10
      mg mL(-1) CNFs and 0.05 mg mL(-1) RNTs). Factors that may have increased
      cardiomyocyte functions include greater wettability, conductivity, and an
      increase in surface nanoroughness with greater amounts of CNFs and RNTs. In
      effect, contact angles measured on the surface of the composites decreased while
      the conductivity and surface roughness increased as CNFs and RNTs content
      increased. Lastly, the ultimate tensile modulus decreased for composites with
      greater amounts of CNFs. In summary, the properties of these injectable
      composites make them promising candidates for myocardial tissue engineering
      applications and should be further studied.

PMID- 23008180
TI  - Losing the struggle to stay awake: divergent thalamic and cortical activity
      during microsleeps.
AB  - Maintaining alertness is critical for safe and successful performance of most
      human activities. Consequently, microsleeps during continuous visuomotor tasks,
      such as driving, can be very serious, not only disrupting performance but
      sometimes leading to injury or death due to accidents. We have investigated the
      neural activity underlying behavioral microsleeps--brief (0.5-15 s) episodes of
      complete failure to respond accompanied by slow eye-closures--and EEG theta
      activity during drowsiness in a continuous task. Twenty healthy normally-rested
      participants performed a 50-min continuous tracking task while fMRI, EEG, eye
      video, and responses were simultaneously recorded. Visual rating of performance
      and eye-video revealed that 70% of the participants had frequent microsleeps.
      fMRI analysis revealed a transient decrease in thalamic, posterior cingulate, and
      occipital cortex activity and an increase in frontal, posterior parietal, and
      parahippocampal activity during microsleeps. The transient activity was modulated
      by the duration of the microsleep. In subjects with frequent microsleeps, power
      in the post-central EEG theta was positively correlated with the BOLD signal in
      the thalamus, basal forebrain, and visual, posterior parietal, and prefrontal
      cortices. These results provide evidence for distinct neural changes associated
      with microsleeps and with EEG theta activity during drowsiness in a continuous
      task. They also suggest that the occurrence of microsleeps during an active task
      is not a global deactivation process but involves localized activation of fronto
      parietal cortex, which, despite a transient loss of arousal, may constitute a
      mechanism by which these regions try to restore responsiveness.

PMID- 23008179
TI  - Imaging nigral pathology and clinical progression in Parkinson's disease.
AB  - The pattern of dopamine cell loss in Parkinson's disease (PD) is known to be
      prominent in the ventrolateral and caudal substantia nigra (SN), but less severe
      in the dorsal and rostral region. Both diffusion tensor imaging (DTI) and R2*
      relaxometry of the SN have been reported as potential markers for PD, but their
      relative ability to mark disease progression and differences in
      pathophysiological bases remains unclear. High-resolution T2-weighted, R2*, and
      DTI were obtained from 28 controls and 40 PD subjects [15 early stage [disease
      duration <=1 year], 14 mid stage [duration 2-5 years], and 11 late stage
      [duration >5 years]). Fractional anisotropy and R2* values in both rostral and
      caudal SN were obtained for all subjects, and clinical measures (e.g., disease
      duration, levodopa-equivalent daily dosage, and "off"-drug UPDRS motor score)
      were obtained for Parkinson's subjects. There was no correlation between
      fractional anisotropy and clinical measures, whereas R2* was strongly associated
      with disease progression. Compared to controls, fractional anisotropy in caudal
      SN was significantly decreased in PD patients of all stages, whereas in rostral
      SN, it was decreased significantly only in the late-stage group. R2* in both SN
      regions was significantly increased in the mid- and late-stage, but not early
      stage, of PD subjects. These findings suggest that fractional anisotropy changes
      may mark early pathological changes in caudal SN, whereas the changes in R2* may
      more closely track PD's clinical progression after symptom onset.

PMID- 23008181
TI  - A native-chemical-ligation-mechanism-based ratiometric fluorescent probe for
      aminothiols.
AB  - Thiol-containing amino acids (aminothiols) such as cysteine (Cys) and
      homocysteine (Hcy) play a key role in various biological processes including
      maintaining the homeostasis of biological thiols. However, abnormal levels of
      aminothiols are associated with a variety of diseases. The native chemical
      ligation (NCL) reaction has attracted great attention in the fields of chemistry
      and biology. NCL of peptide segments involves cascade reactions between a peptide
      alpha-thioester and an N-terminal cysteine peptide. In this work, we employed the
      NCL reaction mechanism to formulate a Forster resonance energy transfer (FRET)
      strategy for the design of ratiometric fluorescent probes that were selective
      toward aminothiols. On the basis of this new strategy, the ratiometric
      fluorescent probe 1 for aminothiols was judiciously designed. The new probe is
      highly selective toward aminothiols over other thiols and exhibits a very large
      variation (up to 160-fold) in its fluorescence ratio (I(458)/I(603)). The new
      fluorescent probe is capable of ratiometric detection of aminothiols in newborn
      calf and human serum samples and is also suitable for ratiometric fluorescent
      imaging of aminothiols in living cells.

PMID- 23008182
TI  - Transseptal approach for the management of paravalvular regurgitation after
      transcatheter aortic valve replacement.
AB  - In the era of transcatheter aortic valve therapies, the presence of residual
      paravalvular regurgitation (PVR) after transcatheter aortic valve replacement
      (TAVR) may become a clinical challenge. Management of late symptomatic PVR is
      still unknown. We describe a challenging case of percutaneous closure attempt of
      a clinically significant PVR in a patient after Edwards SAPIEN (Edwards
      Lifesciences, CA) TAVR.

PMID- 23008183
TI  - Water-stable electrospun collagen fibers from a non-toxic solvent and
      crosslinking system.
AB  - Cytocompatible and water-stable ultrafine collagen fibers were electrospun by
      dissolving collagen in a low corrosive ethanol-water solvent and crosslinked by
      citric acid (CA) with glycerol as the crosslinking extender. Conventional
      solvents used for electrospinning of collagen either cause denaturation or
      contain more than 50% salt potentially leading to poor mechanical properties and
      water stability of the scaffolds. Collagen scaffolds have to be modified by
      techniques, such as, crosslinking to overcome the limitations in strength and
      stability. However, the existing crosslinking methods are either cytotoxic or
      ineffective. In this research, a benign ethanol-water solvent system and an
      extender-aided CA crosslinking method were developed. The native collagen
      conformation was retained after electrospinning, and the dry/wet strengths and
      water stability of fibers were substantially enhanced after crosslinking. The
      crosslinked electrospun scaffolds could maintain their fibrous structure for up
      to 30 days in phosphate-buffered saline at 37 degrees C. Cells exhibited better
      attachment and growth on the CA crosslinked collagen fibers than on the
      glutaraldehyde crosslinked scaffolds.

PMID- 23008184
TI  - Real and imaginary gait.

PMID- 23008185
TI  - Condom use among sexually active rural high school adolescents personal,
      environmental, and behavioral predictors.
AB  - Adolescents who engage in unprotected intercourse are at risk of pregnancy and
      sexually transmitted infection (STI). Although adolescents in rural areas
      participate in levels of sexual risk taking similar to that of nonrural youth,
      few data are available identifying factors that influence condom use among rural
      adolescents. The purpose of this study is to determine the predictive value of
      selected personal, environmental, and behavioral factors for condom use among
      rural adolescents in grades 9-12. A cross-sectional survey was conducted among
      sexually active youth (N = 613), ages 14-19, in three rural school districts in
      the Northeast. Using logistic regression, identified predictors for condom use
      include personal standards (odds ratio [OR] = 2.45; confidence interval [CI]:
      [2.39, 6.47]), condom use goals (OR = 1.32; CI [1.21, 1.45]), condom use at first
      intercourse (OR = 3.93; CI [2.39, 6.47]) and male gender. School nurses are
      encouraged to incorporate identified predictors of condom use when considering
      interventions promoting safer sexual behaviors among rural youth.

PMID- 23008186
TI  - Differences in risk factors for suicide attempts among 9th and 11th grade youth:
      a longitudinal perspective.
AB  - The purpose of the study is to assess the relationship between timing of
      adolescent development and risk factors for suicide. Nationally representative
      data from the Add Health survey were used. The relationship of sociodemographic
      characteristics, known risk factors, and physical developmental timing and
      cognitive developmental style to suicide attempt was assessed. Depression was a
      risk factor for suicide attempts in both 9th and 11th grade. Other risk factors
      differed. Use of illegal drugs, homosexual orientation, using public assistance,
      and physical development were the important risk factors for ninth graders. For
      11th graders, sexual abuse, being in counseling, and being of "other" race or
      ethnicity (mainly Asian or Native American) were risk factors. The cognitive
      development variable of using a systematic problem-solving method was protective
      for 11th graders. Recognizing that risk factors for adolescent suicide attempts
      change over time and with developmental timing of puberty is an important factor
      for suicide prevention strategies.

PMID- 23008187
TI  - Network-based analysis reveals stronger local diffusion-based connectivity and
      different correlations with oral language skills in brains of children with high
      functioning autism spectrum disorders.
AB  - Neuroimaging has uncovered both long-range and short-range connectivity
      abnormalities in the brains of individuals with autism spectrum disorders (ASD).
      However, the precise connectivity abnormalities and the relationship between
      these abnormalities and cognition and ASD symptoms have been inconsistent across
      studies. Indeed, studies find both increases and decreases in connectivity,
      suggesting that connectivity changes in the ASD brain are not merely due to
      abnormalities in specific connections, but rather, due to changes in the
      structure of the network in which the brain areas interact (i.e., network
      topology). In this study, we examined the differences in the network topology
      between high-functioning ASD patients and age and gender matched typically
      developing (TD) controls. After quantitatively characterizing the whole-brain
      connectivity network using diffusion tensor imaging (DTI) data, we searched for
      brain regions with different connectivity between ASD and TD. A measure of oral
      language ability was then correlated with the connectivity changes to determine
      the functional significance of such changes. Whole-brain connectivity measures
      demonstrated greater local connectivity and shorter path length in ASD as
      compared to TD. Stronger local connectivity was found in ASD, especially in
      regions such as the left superior parietal lobule, the precuneus and angular
      gyrus, and the right supramarginal gyrus. The relationship between oral language
      ability and local connectivity within these regions was significantly different
      between ASD and TD. Stronger local connectivity was associated with better
      performance in ASD and poorer performance in TD. This study supports the notion
      that increased local connectivity is compensatory for supporting cognitive
      function in ASD.

PMID- 23008188
TI  - Transcatheter access route options for treatment of degenerated mitral valve
      prosthesis with a balloon-expandable biological valve.
AB  - OBJECTIVES: There is an ongoing discussion if valve-in-valve implantations into
      failing mitral xenografts should be performed only via a transapical approach.
      BACKGROUND: In selected high-risk patients, transcatheter valve implantation is
      an emerging therapy for degenerated mitral xenografts in need of repeated valve
      replacement. METHODS: Here we describe three different strategies to treat a
      failing mitral biological prosthesis (Carpentier Edwards S.A.V) by implantation
      of a SAPIEN-XT valve, which was performed in three different patients. As access
      site, a transjugular/transseptal approach, a transfemoral/transseptal approach,
      and a transapical approach were chosen. RESULTS: With all three approaches, valve
      in-valve implantation was successfully achieved. The acute hemodynamic effects
      were excellent and according to VARC there was no adverse event recorded during a
      6 months follow-up. CONCLUSIONS: Feasibility of all three approaches is
      demonstrated and might be taken into consideration for treatment in various
      patients.

PMID- 23008189
TI  - Photophysical analysis of 1,10-phenanthroline-embedded porphyrin analogues and
      their magnesium(II) complexes.
AB  - The synthesis, characterization, photophysical properties, and theoretical
      analysis of a series of tetraaza porphyrin analogues (H-Pn: n=1-4) containing a
      dipyrrin subunit and an embedded 1,10-phenanthroline subunit are described. The
      meso-phenyl-substituted derivative (H-P1) interacts with a Mg(2+) salt (e.g.,
      MgCl(2), MgBr(2), MgI(2), Mg(ClO(4))(2), and Mg(OAc)(2)) in MeCN solution,
      thereby giving rise to a cation-dependent red-shift in both the absorbance- and
      emission maxima. In this system, as well as in the other H-Pn porphyrin analogues
      used in this study, the four nitrogen atoms of the ligand interact with the bound
      magnesium cation to form Mg(2+)-dipyrrin-phenanthroline complexes of the general
      structure MgX-Pn (X=counteranion). Both single-crystal X-ray diffraction analysis
      of the corresponding zinc-chloride derivative (ZnCl-P1) and fluorescence
      spectroscopy of the Mg-adducts that are formed from various metal salts provide
      support for the conclusion that, in complexes such as MgCl-P1, a distorted square
      pyramidal geometry persists about the metal cation wherein a chloride anion acts
      as an axial counteranion. Several analogues (H?Pn) that contain electron-donating
      and/or electron-withdrawing dipyrrin moieties were prepared in an effort to
      understand the structure-property relationships and the photophysical attributes
      of these Mg-dipyrrin complexes. Analysis of various MgX-Pn (X=anion) systems
      revealed significant substitution effects on their chemical, electrochemical, and
      photophysical properties, as well as on the Mg(2+)-cation affinities. The
      fluorescence properties of MgCl-Pn reflected the effect of donor-excited
      photoinduced electron transfer (d-PET) processes from the dipyrrin subunit (as a
      donor site) to the 1,10-phenanthroline acceptor subunit. The proposed d-PET
      process was analyzed by electron paramagnetic resonance (EPR) spectroscopy and by
      femtosecond transient absorption (TA) spectroscopy, as well as by theoretical DFT
      calculations. Taken together, these studies provide support for the suggestion
      that a radical species is produced as the result of an intramolecular charge
      transfer process, following photoexcitation. These photophysical effects,
      combined with a mixed dipyrrin-phenanthroline structure that is capable of
      effective Mg(2+)-cation complexation, lead us to suggest that porphyrin-inspired
      systems, such as H?Pn, have a role to play as magnesium-cation sensors.

PMID- 23008190
TI  - Improving the packing density of calcium phosphate coating on a magnesium alloy
      for enhanced degradation resistance.
AB  - In this study, an attempt was made to improve the packing density of calcium
      phosphate (CaP) coating on a magnesium alloy by tailoring the coating solution
      for enhanced degradation resistance of the alloy for implant applications. An
      organic solvent, ethanol, was added to the coating solution to decrease the
      conductivity of the coating solution so that hydrogen bubble formation/bursting
      reduces during the CaP coating process. Experimental results confirmed that
      ethanol addition to the coating solution reduces the conductivity of the solution
      and also decreases the hydrogen evolution/bubble bursting. In vitro
      electrochemical experiments, that is, electrochemical impedance spectroscopy
      (EIS) and potentiodynamic polarization showed that CaP coating produced in 30%
      (v/v) ethanol containing coating solution (3E) exhibits significantly higher
      degradation resistance (i.e., ~50% higher polarization resistance and ~60% lower
      corrosion current) than the aqueous solution coating. Scanning electron
      microscope (SEM) analysis of the coatings revealed that the packing of 3E coating
      was denser than that of aqueous coating, which can be attributed to the lower
      hydrogen evolution in the former than in the latter. Further increase in the
      ethanol content in the coating solution was not beneficial; in fact, the coating
      produced in 70% (v/v) ethanol containing solution (7E) showed degradation
      resistance much inferior to that of the aqueous coating, which is due to low
      thickness of 7E coating.

PMID- 23008191
TI  - Evidence for central sensitization in chronic whiplash: a systematic literature
      review.
AB  - BACKGROUND AND OBJECTIVES: It has been suggested that sensitization of the
      central nervous system plays an important role in the development and maintenance
      of chronic (pain) complaints experienced by whiplash patients. According to the
      PRISMA guidelines, a systematic review was performed to screen and evaluate the
      existing clinical evidence for the presence of central sensitization in chronic
      whiplash. DATABASES AND DATA TREATMENT: Predefined keywords regarding central
      sensitization and chronic whiplash were combined in electronic search engines
      PubMed and Web of Science. Full text clinical reports addressing studies of
      central sensitization in human adults with chronic complaints due to a whiplash
      trauma were included and reviewed on methodological quality by two independent
      reviewers. RESULTS: From the 99 articles that were identified, 24 met the
      inclusion criteria, and 22 articles achieved sufficient scores on methodological
      quality and were discussed. These studies evaluated the sensitivity to different
      types of stimuli (mechanical, thermal, electrical). Findings suggest that
      although different central mechanisms seem to be involved in sustaining the pain
      complaints in whiplash patients, hypersensitivity of the central nervous system
      plays a significant role. Persistent pain complaints, local and widespread
      hyperalgesia, referred pain and (thoracic) allodynia, decreased spinal reflex
      thresholds, inefficient diffuse noxious inhibitory controls activation and
      enhanced temporal summation of pain were established in chronic whiplash
      patients. CONCLUSIONS: Although the majority of the literature provides evidence
      for the presence of central sensitization in chronic whiplash, underlying
      mechanisms are still unclear and future studies with good methodological quality
      are necessary. In addition, international guidelines for the definition, clinical
      recognition, assessment and treatment of central sensitization are warranted.

PMID- 23008192
TI  - A highly active bifunctional iridium complex with an alcohol/alkoxide-tethered N
      heterocyclic carbene for alkylation of amines with alcohols.
AB  - A series of new iridium(III) complexes containing bidentate N-heterocyclic
      carbenes (NHC) functionalized with an alcohol or ether group (NHC-OR, R = H, Me)
      were prepared. The complexes catalyzed the alkylation of anilines with alcohols
      as latent electrophiles. In particular, biscationic Ir(III) complexes of the type
      [Cp*(NHC-OH)Ir(MeCN)](2+)2[BF(4)(-)] afforded higher-order amine products with
      very high efficiency; up to >99% yield using a 1:1 ratio of reactants and 1-2.5
      mol % of Ir, in short reaction times (2-16 h) and under base-free conditions.
      Quantitative yields were also obtained at 50  degrees C, although longer reaction
      times (48-60 h) were needed. A large variety of aromatic amines have been
      alkylated with primary and secondary alcohols. The reactivity of structurally
      related iridium(III) complexes was also compared to obtain insights into the
      mechanism and into the structure of possible catalytic intermediates. The Ir(III)
      complexes were stable towards oxygen and moisture, and were characterized by NMR,
      HRMS, single-crystal X-ray diffraction, and elemental analyses.

PMID- 23008193
TI  - Single-center comparative outcomes of the Edwards SAPIEN and Medtronic Melody
      transcatheter heart valves in the pulmonary position.
AB  - BACKGROUND: Two transcatheter pulmonary valve replacement (tPVR) systems (Edwards
      SAPIEN and Medtronic Melody) are available; however, comparative studies
      evaluating outcome data are lacking. The aim of this study was to compare short-
      with medium-term outcome data of these valves in the pulmonary position from a
      single institution. METHODS: Retrospective data analysis of all patients
      undergoing tPVR from April 2008 until April 2012. Pre-procedural investigations,
      patient demographics, procedural hemodynamics, and clinical and echocardiographic
      follow-up data were included. Data are presented as mean +/- standard deviation.
      RESULTS: Thirty-three patients underwent successful tPVR (SAPIEN (S) n = 20,
      Melody (M) n = 13). Patient age and weight were similar between the two groups.
      Primary indication included regurgitation (S (n = 2), M (n = 3)), stenosis (S (n
      = 13), M (n = 7)), or mixed (S (n = 5), M (n = 3)). There was no difference in
      pre-procedural peak Doppler gradients across the pulmonary outflow (S = 47.73 +/-
      21.14 mm Hg, M = 42.62 +/- 15.59 mm Hg, P = 0.46). All but one patient underwent
      pre-stenting prior to valve implantation. Immediately following valve deployment,
      the transvalvar gradient was not statistically different between the two groups
      (S = 11.5 +/- 8.07 mm Hg, M = 8.15 +/- 4.56 mm Hg, P = 0.18). There were no
      procedural deaths. Follow-up mean pulmonary Doppler gradients were higher with
      the SAPIEN cohort (18.43 +/- 9.06 mm Hg (S) and 11.17 +/- 5.24 mm Hg (M), P =
      0.016); however, no differences were seen when similar procedural epochs were
      assessed. All but one patient remained with PR grade = 2. CONCLUSIONS: In a
      single-center series, the SAPIEN and Melody valves demonstrated comparable medium
      term valve function. Greater residual gradients with the SAPIEN valve may
      represent a more conservative early pre-stenting approach with this valve.

PMID- 23008194
TI  - Cellular uptake of covalent poly(allylamine hydrochloride) microcapsules and its
      influences on cell functions.
AB  - The mechanism of the cellular uptake of polyelectrolyte microcapsules and its
      influences on the functions and toxicity of human SMCs are explored. The
      covalently assembled poly(allylamine hydrochloride)/glutaraldehyde microcapsules
      are easily ingested by SMCs mainly through macropinosis and caveolae-mediated
      endocytosis pathways. The capsules mainly disperse in cytoplasm without
      colocalization in early endosomes and cell nucleus. The results of gene chips
      reveal substantial and profound alternation of cell phenotypes and functions.
      Uptake of the microcapsules cause a slight decrease of cell viability, but leads
      to significant changes in cytoskeleton organization, cell cycle, as well as cell
      adhesion and migration ability.

PMID- 23008195
TI  - Genetic variants in the catechol-o-methyltransferase gene are associated with
      impulsivity and executive function: relevance for major depression.
AB  - The catechol-o-methyltransferase (COMT) gene has been extensively investigated in
      depression with somewhat contradictory results but the role of impulsivity, as a
      possible intermediate phenotype in this disorder, has not been considered yet. In
      our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680,
      rs4646316) were genotyped in two independent population cohorts: Manchester (n =
      1267) and Budapest (n = 942). First, we investigated the association between COMT
      genotypes, impulsivity, neuroticism and depression using haplotype trend
      regression, and constructed a model using structural equation modeling to
      investigate the interaction between these factors. Secondly, we tested the effect
      of executive function on this model in a smaller interviewed sample (n = 207).
      Our results demonstrated that COMT haplotypes were significantly associated with
      impulsivity in the combined cohort, showing the same direction of effects in both
      populations. The COMT effect on depressive symptoms (in subjects without history
      of depression) and on executive function (interviewed sample) showed the opposite
      pattern to impulsivity. Structural equation models demonstrated that COMT and
      impulsivity acted, both together (through neuroticism) and independently, to
      increase the risk of depression. In addition, better executive function also
      operated as a risk factor for depression, possibly though reduced ability to
      flexibly disengage negative emotions. In conclusion, variations in the COMT gene
      exert complex effects on susceptibility to depression involving various
      intermediate phenotypes, such as impulsivity and executive function. These
      findings emphasise that modeling of disease pathways at phenotypic level are
      valuable for identifying genetic risk factors.

PMID- 23008196
TI  - Coronal ultrasound anatomy of a normal hip in a newborn baby.

PMID- 23008197
TI  - Evidence based medicine inevitably increases testosterone prescribing.

PMID- 23008198
TI  - NHS health checks and QOF increase overtreatment.

PMID- 23008199
TI  - Coronial postmortem samples and public health.

PMID- 23008200
TI  - Current diabetes services in England need to be reorganised.

PMID- 23008201
TI  - Partnership working is key to providing seamless care.

PMID- 23008202
TI  - Pregnancy after bariatric surgery does not affect weight loss.

PMID- 23008203
TI  - Historical footnote on the treatment of mild hypertension.

PMID- 23008204
TI  - A major rethink is needed on reporting adverse drug reactions.

PMID- 23008205
TI  - Local efforts are paramount in preventing suicide during recession.

PMID- 23008206
TI  - Deliberate ingestion of "magic" mushrooms may also cause renal failure.

PMID- 23008207
TI  - If in doubt, don't eat it.

PMID- 23008208
TI  - Give potential donors priority for receipt of an organ.

PMID- 23008209
TI  - More red tape will make organ shortage worse.

PMID- 23008210
TI  - How does bariatric surgery affect female fertility?

PMID- 23008211
TI  - Patient with new strain of coronavirus is treated in intensive care at London
      hospital.

PMID- 23008212
TI  - NHS can't be expected to continue plugging gaps in social care funding, says NHS
      Confederation.

PMID- 23008213
TI  - The inactivation mechanism of human group IIA phospholipase A(2) by Scalaradial.
AB  - Secretory phospholipases A(2) (sPLA(2)s) are implicated in the pathogenesis of
      several inflammation diseases, such as rheumatoid arthritis, septic shock,
      psoriasis, and asthma. Thus, an understanding of their inactivation mechanisms
      could be useful for the development of new classes of chemical selective
      inhibitors. In the marine environment, several bioactive terpenoids possess
      interesting anti-inflammatory activity, often through covalent and/or noncovalent
      inactivation of sPLA(2). Herein, we report the molecular mechanism of human group
      IIA phospholipase A(2) (sPLA(2)-IIA) inactivation by Scalaradial (SLD), a marine
      1,4-dialdehyde terpenoid isolated from the sponge Cacospongia mollior and endowed
      with a significant anti-inflammatory profile. Our results have been collected by
      a combination of biochemical approaches, advanced mass spectrometry, surface
      plasmon resonance, and molecular modeling. These suggest that SLD acts as a
      competitive inhibitor. Indeed, the sPLA(2)-IIA inactivation process seems to be
      driven by the noncovalent recognition process of SLD in the enzyme active site
      and by chelation of the catalytic calcium ion. In contrast, covalent modification
      of the enzyme by the SLD dialdehyde moiety emerges as only a minor side event in
      the ligand-enzyme interaction. These results could be helpful for the rational
      design of new PLA(2) inhibitors that would be able to selectively target the
      enzyme active site.

PMID- 23008214
TI  - Understanding the solvent effect on the catalytic oxidation of 1,4-butanediol in
      methanol over Au/TiO2 catalyst: NMR diffusion and relaxation studies.
AB  - The effect of water on the catalytic oxidation of 1,4-butanediol in methanol over
      Au/TiO(2) has been investigated by catalytic reaction studies and NMR diffusion
      and relaxation studies. The addition of water to the dry catalytic system led to
      a decrease of both conversion and selectivity towards dimethyl succinate. Pulsed
      field gradient (PFG)-NMR spectroscopy was used to assess the effect of water
      addition on the effective self-diffusivity of the reactant within the catalyst.
      NMR relaxation studies were also carried out to probe the strength of surface
      interaction of the reactant in the absence and presence of water. PFG-NMR studies
      revealed that the addition of water to the initial system, although increasing
      the dilution of the system, leads to a significant decrease of effective
      diffusion rate of the reactant within the catalyst. From T(1) and T(2) relaxation
      measurements it was possible to infer the strength of surface interaction of the
      reactant with the catalyst surface. The addition of water was found to inhibit
      the adsorption of the reactant over the catalyst surface, with the T(1)/T(2)
      ratio of 1,4-butanediol decreasing significantly when water was added. The
      results overall suggest that both the decrease of diffusion rate and adsorption
      strength of the reactant within the catalyst, due to water addition, limits the
      access of reactant molecules to the catalytic sites, which results in a decrease
      of reaction rate and conversion.

PMID- 23008215
TI  - Antimicrobial hydantoin-grafted poly(epsilon-caprolactone) by ring-opening
      polymerization and click chemistry.
AB  - Novel degradable and antibacterial polycaprolactone-based polymers are reported
      in this work. The polyesters with pendent propargyl groups are successfully
      prepared by ring-opening polymerization and subsequently used to graft
      antibacterial hydantoin moieties via click chemistry by a copper(I)-catalyzed
      azide-alkyne cycloaddition reaction. The well-controlled chemical structures of
      the grafted copolymers and its precursors are verified by FT-IR spectroscopy, NMR
      spectroscopy, and GPC characterizations. According to the DSC and XRD results,
      the polymorphisms of these grafted copolymers are mostly changed from
      semicrystalline to amorphous depending on the amount of grafted hydantoin.
      Antibacterial assays are carried out with Bacillus subtilis and two strains of
      Escherichia coli and show fast antibacterial action.

PMID- 23008216
TI  - Three-dimensional intravascular ultrasound evaluation of carina and plaque shift
      at the distal left main coronary artery bifurcation after treatment with a one
      stent cross-over technique.
AB  - OBJECTIVE: To assess the geometrical changes in the distal left main coronary
      artery (LMCA), left anterior descending (LAD), and left circumflex (LCX) that
      occur after a distal LMCA lesion is treated using a one-stent cross-over
      strategy. BACKGROUND: Morphological changes after stent implantation into distal
      LMCA lesions are not fully understood. METHODS: We used pre- and postintervention
      three-dimensional intravascular ultrasound of both the LAD and LCX as well as of
      the LMCA to evaluate distal LMCA lesions after a 1-stent cross-over strategy. In
      38 distal LMCA bifurcation lesions, cross-sectional measurements were performed
      every 1 mm over a 5-mm segment in the LAD and LCX distal to the carina and over
      the entire LMCA proximal to the carina. RESULTS: The increase in lumen volume
      correlated with the increase in external elastic membrane volumes: R = 0.917, P <
      0.001, in the LMCA and R = 0.785, P < 0.001, in the LAD with no decrease in
      plaque volume except at the distal end of the LMCA (P = 0.081) and at the LAD
      carina (P = 0.11). The LCX lumen area decreased significantly at the LCX carina
      from 5.9 +/- 2.0 mm(2) to 5.3 +/- 1.9 mm(2) (P < 0.01); however, the response was
      variable from a 4.0 mm(2) decrease to a 1.8 mm(2) increase in lumen area. While
      the change in LCX lumen area at the carina correlated with the change in vessel
      area (R = 0.791, P < 0.001), there was also a small increase in plaque area at
      the LCX carina from 6.4 +/- 2.9 mm(2) to 6.8 +/- 2.9 mm(2) (P < 0.01).
      CONCLUSIONS: LMCA bifurcation lumen changes after cross-over single-stent
      implantation were determined primarily by conformational changes in vessel
      geometry.

PMID- 23008217
TI  - Sulfonyl fluoride analogues as activity-based probes for serine proteases.
AB  - Enriched with fluoride: To expand on the available tools to interrogate
      proteases, we explored sulfonyl fluorides as activity-based probes. An alkyne
      tagged sulfonyl fluoride covalently modifies members of the S1 family of serine
      proteases. By applying click chemistry, avidin enrichment and mass spectrometry,
      we can enrich and identify active endogenous serine proteases from a complex
      proteome.

PMID- 23008218
TI  - Construction of chlorosomal rod self-aggregates in the solid state on any
      substrates from synthetic chlorophyll derivatives possessing an oligomethylene
      chain at the 17-propionate residue.
AB  - Chlorosomes are one of the most unique natural light-harvesting antennas and
      their supramolecular nanostructures are still under debate. Chlorosomes contain
      bacteriochlorophyll (BChl)-c, d and e molecules and these pigments self-aggregate
      under a hydrophobic environment inside a chlorosome. The self-aggregates are
      mainly constructed by the following three interactions: hydrogen bonding,
      coordination bonding and pi-pi stacking. Supramolecular nanostructures of self
      aggregated BChls have been widely investigated by spectroscopic and microscopic
      techniques. Model compounds of such chlorosomal BChl molecules have been
      synthesized and the effects of esterified long alkyl chains at the 17-propionate
      residue for their self-aggregation have been studied. Structurally simple zinc
      chlorophyll derivatives possessing an oligomethylene chain as the esterifying
      group at the 17-propionate residue were prepared as chlorosomal BChl models. The
      synthetic zinc BChls self-aggregated in nonpolar organic solvents to give
      precipitates. The resulting insoluble self-aggregated solids were investigated on
      a variety of substrates, including hydrophobic, neutral and hydrophilic
      substrates, by visible absorption, circular dichroism and polarized light
      absorption spectroscopies, as well as atomic force, transmission electron and
      scanning electron microscopies. The self-aggregates of synthetic Zn-BChls formed
      rods with an approximately 5 nm diameter and wires with further elongated growth
      of the rods (aspect ratio >200). The diameter size was consistent with that
      estimated for natural chlorosomal rods in a filamentous anoxygenic phototroph,
      Chloroflexus aurantiacus. The supramolecular formation and stability of the rod
      on the examined substrates depended on the length of an oligomethylene chain at
      the 17-propionate residue as well as on the surface properties. Especially, the
      number of the 5 nm rods on the substrates increased with an elongation of the
      chain.

PMID- 23008219
TI  - Spectroscopic study of the interaction between lycopene and bovine serum albumin.
AB  - The interaction of lycopene with bovine serum albumin (BSA) in aqueous solution
      was studied by fluorescence quenching, three-dimensional fluorescence and
      circular dichroism spectroscopy. The data showed that the fluorescence of BSA was
      quenched by lycopene at different temperatures through a dynamic mechanism. The
      evaluation of three-dimensional fluorescence spectra revealed a conformational
      modification of BSA induced by coupling with lycopene and an increase in protein
      diameter as a consequence of the ligand-protein interaction. Moreover, the
      information obtained from evaluation of the effect of lycopene on BSA
      conformation by circular dichroism strongly supported the existence of a slight
      unfolding of BSA induced by coupling to lycopene.

PMID- 23008221
TI  - Giant spinal cord ependymoma with CSF spread.

PMID- 23008220
TI  - Vitamin D, cognition, and dementia: a systematic review and meta-analysis.
AB  - OBJECTIVE: To examine the association between cognitive function and dementia
      with vitamin D concentration in adults. METHODS: Five databases were searched for
      English-language studies up to August 2010, and included all study designs with a
      comparative group. Cognitive function or impairment was defined by tests of
      global or domain-specific cognitive performance and dementia was diagnosed
      according to recognized criteria. A vitamin D measurement was required. Two
      authors independently extracted data and assessed study quality using predefined
      criteria. The Q statistic and I2 methods were used to test for heterogeneity. We
      conducted meta-analyses using random effects models for the weighted mean
      difference (WMD) and Hedge's g. RESULTS: Thirty-seven studies were included; 8
      contained data allowing mean Mini-Mental State Examination (MMSE) scores to be
      compared between participants with vitamin D <50 nmol/L to those with values >=50
      nmol/L. There was significant heterogeneity among the studies that compared the
      WMD for MMSE but an overall positive effect for the higher vitamin D group (1.2,
      95% confidence interval [CI] 0.5 to 1.9; I2 = 0.65; p = 0.002). The small
      positive effect persisted despite several sensitivity analyses. Six studies
      presented data comparing Alzheimer disease (AD) to controls but 2 utilized a
      method withdrawn from commercial use. For the remaining 4 studies the AD group
      had a lower vitamin D concentration compared to the control group (WMD = -6.2
      nmol/L, 95% CI -10.6 to -1.8) with no heterogeneity (I2 < 0.01; p = 0.53).
      CONCLUSION: These results suggest that lower vitamin D concentrations are
      associated with poorer cognitive function and a higher risk of AD. Further
      studies are required to determine the significance and potential public health
      benefit of this association.

PMID- 23008222
TI  - Predicting outcome after acute basilar artery occlusion based on admission
      characteristics.

PMID- 23008225
TI  - Emerging subspecialties in neurology: fellowship in experimental therapeutics of
      neurologic disease.

PMID- 23008223
TI  - Evidence-based guideline: IV immunoglobulin in the treatment of neuromuscular
      disorders: report of the Therapeutics and Technology Assessment Subcommittee of
      the American Academy of Neurology.

PMID- 23008226
TI  - Mystery case: hypoglossal nerve palsy in occipito-temporal pneumatization.

PMID- 23008227
TI  - Teaching neuroimages: hemispheric epilepsy.

PMID- 23008228
TI  - Infant colic and migraine: is there a connection?

PMID- 23008229
TI  - Bonding and electronic transport properties of fullerene and fullerene
      derivatives in break-junction geometries.
AB  - Fullerenes are considered anchoring groups for molecular electronics due to a
      large contact area and their affinity for noble metals. The conductances of
      fullerene-terminated molecules, however, are found to be even lower than for
      thiol termination. The effects of weak molecule-metal coupling and symmetry
      breaking are studied by transport measurements of C(60) and functionalized C(60).
      The results demonstrate highy efficient contacts between Au and C(60), despite of
      deposition from solution.

PMID- 23008230
TI  - Novel assembly of an MoS2 electrocatalyst onto a silicon nanowire array electrode
      to construct a photocathode composed of elements abundant on the earth for
      hydrogen generation.
AB  - Mild-mannered catalyst: a novel procedure to load a MoS(2) co-catalyst onto the
      surface of silicon under mild-conditions (room temperature, atmospheric pressure,
      aqueous solution) by a photo-assisted electrodeposition process employing
      commercially available precursors is reported. The obtained Si-NW@MoS(2)
      photocathode showed similar catalytic activity for light-driven H(2) generation
      compared with a Si-NW@Pt photocathode.

PMID- 23008231
TI  - A chemiluminescent metalloimmunoassay based on copper-enhanced gold nanoparticles
      for quantification of human growth hormone.
AB  - A chemiluminescence (CL) immunoassay was developed to determine human growth
      hormone (hGH) based on copper-enhanced gold nanoparticles. In this method, gold
      nanoparticles were deposited on polystyrene wells for adsorption of human growth
      antibodies as well as catalyst for reducing of copper ions from the copper
      enhancer solution. The reduction of copper ions was prevented where the gold
      nanoparticles were covered by the antibody-antigen immunocomplex. The deposited
      copper on Au nanoparticles was then dissolved in HNO3 solution and quantified
      using the CL method. The CL intensity response was logarithmically dependent on
      the hGH concentrations over the range 0.2-50 ng/mL, with a detection limit
      (3sigma) of 0.036 ng/mL.

PMID- 23008232
TI  - Reaction-based colorimetric and ratiometric fluorescence sensor for detection of
      cyanide in aqueous media.
AB  - A stilbene-based compound (1) has been prepared and was highly selective for the
      detection of cyanide anion in aqueous media even in the presence of other anions,
      such as F(-), Cl(-), Br(-), I(-), ClO(4)(-), H(2)PO(4)(-), HSO(4)(-), NO(3)(-),
      and CH(3)CO(2)(-). A noticeable change in the color of the solution, along with a
      prominent fluorescence enhancement, was observed upon the addition of cyanide.
      The color change was observed upon the nucleophilic addition of the cyanide anion
      to the electron-deficient cyanoacrylate group of 1. The spectral changes induced
      by the reaction were analyzed by comparison with two model compounds, such as
      compound 2 with dimethyl substituents and compound 3 without a cyanoacrylate
      group. An intramolecular charge-transfer (ICT) mechanism played a key role in the
      sensing properties, and the mechanism was supported by DFT/TDDFT calculations.

PMID- 23008233
TI  - Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation.

PMID- 23008234
TI  - Subventricular zone neural progenitors protect striatal neurons from
      glutamatergic excitotoxicity.
AB  - The functional significance of adult neural stem and progenitor cells in
      hippocampal-dependent learning and memory has been well documented. Although
      adult neural stem and progenitor cells in the subventricular zone are known to
      migrate to, maintain and reorganize the olfactory bulb, it is less clear whether
      they are functionally required for other processes. Using a conditional
      transgenic mouse model, selective ablation of adult neural stem and progenitor
      cells in the subventricular zone induced a dramatic increase in morbidity and
      mortality of central nervous system disorders characterized by excitotoxicity
      induced cell death accompanied by reactive inflammation, such as 4-aminopyridine
      induced epilepsy and ischaemic stroke. To test the role of subventricular zone
      adult neural stem and progenitor cells in protecting central nervous system
      tissue from glutamatergic excitotoxicity, neurophysiological recordings of
      spontaneous excitatory postsynaptic currents from single medium spiny striatal
      neurons were measured on acute brain slices. Indeed, lipopolysaccharide
      stimulated, but not unstimulated, subventricular zone adult neural stem and
      progenitor cells reverted the increased frequency and duration of spontaneous
      excitatory postsynaptic currents by secreting the endocannabinod arachidonoyl
      ethanolamide, a molecule that regulates glutamatergic tone through type 1
      cannabinoid receptor (CB(1)) binding. In vivo restoration of cannabinoid levels,
      either by administration of the type 1 cannabinoid receptor agonist HU210 or the
      inhibitor of the principal catabolic enzyme fatty acid amide hydrolase, URB597,
      completely reverted the increased morbidity and mortality of adult neural stem
      and progenitor cell-ablated mice suffering from epilepsy and ischaemic stroke.
      Our results provide the first evidence that adult neural stem and progenitor
      cells located within the subventricular zone exert an 'innate' homeostatic
      regulatory role by protecting striatal neurons from glutamate-mediated
      excitotoxicity.

PMID- 23008235
TI  - Preparation of a stationary phase with quaternary ammonium embedded group for
      selective separation of alkaloids based on ion-exclusion interaction.
AB  - A stationary phase (named QA C10) with quaternary ammonium embedded between a
      propyl and a decyl chain was synthesized by immobilization of N,N
      dimethyldecylamine on chloropropyl-silica surface. A set of representative
      neutral, basic, and acidic compounds was employed to evaluate its chromatographic
      properties. The results illustrated that QA C10 was a mixed-mode stationary phase
      possessing both hydrophobic and ionic characteristics. The QA C10 stationary
      phase was further used for selective separation of alkaloids from Cortex
      phellodendri. Under acidic condition, alkaloids could be eluted in first 8 min,
      while other neutral and acidic fractions were retained better on QA C10 column.
      Then, obtained alkaloid fraction was analyzed by LC-MS/MS and 22 alkaloids were
      identified. Our study confirmed the advantages and application potential of the
      QA C10 stationary phase for alkaloids separation.

PMID- 23008236
TI  - Delineating breast ductal carcinoma using combined dye-enhanced wide-field
      polarization imaging and optical coherence tomography.
AB  - Intra-operative delineation of breast cancer is a challenging problem. We used
      dye-enhanced wide-field polarization imaging for rapid demarcation of en face
      cancer margins and optical coherence tomography (OCT) for cross-sectional
      evaluation. Ductal carcinoma specimens were stained with methylene blue. Wide
      field reflectance images were acquired at 440 and 640 nm. Wide-field fluorescence
      images were excited at 640 nm and registered between 660 nm and 750 nm. OCT
      images were acquired using a 1310 nm swept-source system. The results were
      validated against histopathology. Both imaging modalities provided diagnostic
      information on cancer margins. Combined OCT and wide-field polarization imaging
      shows promise for intra-operative detection of ductal breast carcinoma.

PMID- 23008238
TI  - Don't be so busy making a living that you forget to make a life.

PMID- 23008237
TI  - Andhraxylocarpins A-E: structurally intriguing limonoids from the true mangroves
      Xylocarpus granatum and Xylocarpus moluccensis.
AB  - Five new limonoids, including andhraxylocarpins A and B (1 and 2) which contain a
      9-oxa-tricyclo[3.3.2.1(7, 10)]undecane-2-ene motif, andhraxylocarpins C and D (3
      and 4), which contain a (Z)-bicyclo[5.2.1]dec-3-en-8-one substructure, and
      andhraxylocarpin E (5), which contains a tricyclo[3.3.1.1(3, 6)]decane-9-one
      scaffold, were isolated from the seeds of two true mangroves, Xylocarpus granatum
      and Xylocarpus moluccensis, that were collected in the estuaries of Andhra
      Pradesh, India. The absolute configurations of these compounds were determined by
      extensive NMR investigations, single-crystal X-ray diffraction analysis, and by
      circular dichroism and optical rotatory dispersion spectroscopy, in combination
      with quantum-chemical calculations. The pronounced structural diversity of
      limonoids from these mangroves might originate from environmental factors.

PMID- 23008239
TI  - Rating systems for evaluation of functional ankle instability: prospective
      evaluation in a cohort of patients treated with monopolar capacitive-coupled
      radiofrequency.
AB  - Evaluation of patient outcomes should include the use of validated scoring
      systems to determine disease-specific outcomes. Many scoring systems are being
      used for disorders of the ankle joint. However, not all instruments are capable
      of detecting changes associated with functional ankle instability (FAI), since
      their focus is toward pathological entities with greater impact on individual's
      physical and mental well-being. METHODS: In this prospective study, 6 instruments
      were used to evaluate outcomes associated with an intervention aimed at improving
      FAI. Twenty ankles that had been unsuccessfully treated for FAI were treated with
      a single session of noninvasive monopolar capacitive-coupled radiofrequency
      (mcRF) and followed prospectively. RESULTS: Five out of 6 instruments failed to
      show changes that could be correlated with patients' outcomes. Only one
      instrument, the Cumberland Ankle Instability Tool (CAIT) demonstrated enough
      sensitivity and correlated well with meaningful clinical differences. Based on
      study's success criteria (proper function, no pain, no adverse events, and
      patient satisfaction), 78% of the ankles treated had successful outcomes whereas
      87.5% evidenced significant improvement based on CAIT (P < .001). No adverse
      events were present during the study. CONCLUSIONS: The study of FAI is hampered
      by the lack of disease-specific questionnaires, which oftentimes introduce
      ceiling or flooring effects. The CAIT was capable of detecting changes in
      patients' condition and response to the noninvasive mcRF procedure without
      evidencing ceiling or flooring effects. In this study, the CAIT was found to be
      reliable, valid, sensitive to changes of clinical importance, in addition to
      being short and practical to use.

PMID- 23008240
TI  - A highly enantioselective synthesis of functionalized 2,3-dihydrofurans by a
      modified Feist-Benary reaction.
AB  - Organocatalysis: a modified Feist-Benary reaction employing acyclic beta
      ketoesters as the dinucleophile and (E)-beta,beta-bromo nitrostyrenes as the
      dielectrophile was developed for the asymmetric synthesis of 2,3-dihydrofurans. L
      Threonine-derived tertiary amine/thiourea catalysts were found to be the most
      efficient catalysts, inducing the reaction in a highly enantioselective manner
      (TBDPS=tert-butyldiphenylsilyl).

PMID- 23008241
TI  - Development of a refined tenocyte expansion culture technique for tendon tissue
      engineering.
AB  - The aim of this study was to efficiently expand less differentiated tenocytes
      with minimum use of fetal bovine serum (FBS) for tenocyte-based tendon tissue
      engineering. To achieve this goal, human tenocytes were cultured in different
      concentrations of FBS and combinations of growth factors PDGF(BB), IGF-1 and
      bFGF. A number of growth factors were selected that could support tenocyte
      expansion at reduced differentiated state with minimum FBS usage. Results showed
      that the expansion of the tenocytes cultured for 14 days with 1% FBS, 50 ng/ml
      PDGF(BB) and 50 ng/ml bFGF was similar to that cultured in the 10% FBS control
      group. The tenocytes cultured in the treatment group showed significantly lower
      collagen synthesis and down-regulation of mRNA expression of tendon
      differentiation markers. Cell morphology confirmed that tenocytes cultured in the
      growth factors had reduced collagen fibril formation compared to tenocytes
      cultured in 10% FBS. Our findings confirm the feasibility of inducing human
      tenocyte expansion in vitro with the least amount of FBS usage, while controlling
      their differentiation until required.

PMID- 23008242
TI  - Craniospinal pressure-volume dynamics in phantom models.
AB  - Regulation of intracranial pressure (ICP) is vital to proper brain function.
      Pathologic conditions such as traumatic brain injury and hydrocephalus can cause
      lethal changes in ICP through an imbalance of fluid passage into and out of the
      craniospinal space. The relationship between craniospinal volume and pressure
      determines to a large extent whether such imbalance can be compensated or if it
      will lead to neuronal damage. Phantom models are predisposed for the evaluation
      of medical procedures and devices that alter volume in the spinal or cranial
      space. However, current phantoms have substantial limitations in the reproduction
      of craniospinal pressure-volume relationships, which need to be overcome prior to
      their deployment outside the basic research setting. We present herein a novel
      feedback controlled phantom for the reproduction of any physiologic or pathologic
      pressure-volume relation. We compare its performance to those of existing passive
      methods, showing that it follows reference curves more precisely during both
      infusion of large volumes and fast oscillatory volume changes.

PMID- 23008243
TI  - Perk Tutor: an open-source training platform for ultrasound-guided needle
      insertions.
AB  - Image-guided needle placement, including ultrasound (US)-guided techniques, have
      become commonplace in modern medical diagnosis and therapy. To ensure that the
      next generations of physicians are competent using this technology, efficient and
      effective educational programs need to be developed. This paper presents the Perk
      Tutor: a configurable, open-source training platform for US-guided needle
      insertions. The Perk Tutor was successfully tested in three different
      configurations to demonstrate its adaptability to different procedures and
      learning objectives. 1) The Targeting Tutor, designed to develop US-guided needle
      targeting skills, 2) the Lumbar Tutor, designed for practicing US-guided lumbar
      spinal procedures, and (3) the Prostate Biopsy Tutor, configured for US-guided
      prostate biopsies. The Perk Tutor provides the trainee with quantitative feedback
      on progress toward the specific learning objectives of each configuration.
      Configurations were implemented through simple rearrangement of hardware and
      software components, attesting to the modularity and ease of configuration. The
      Perk Tutor is provided as a free resource to enable research and development of
      educational programs for US-guided intervention.

PMID- 23008244
TI  - Non-contact ECG sensing employing gradiometer electrodes.
AB  - Noncontact, capacitive electrocardiogram (ECG) measurements are complicated by
      motion artifacts from the relative movement between the ECG electrodes and the
      subject. To compensate for such motion we propose to employ first and second
      order gradiometer electrode designs. A MATLAB-based simulation tool to enable
      assessment of different electrode configurations and placements on human subjects
      has been developed to guide the refinement of electrode designs. Experimental
      measurements of the sensitivity, motion artifact cancellation, and common mode
      rejection for various prototype designs were conducted with human subjects.
      Second order gradiometer electrode designs appear to give the best performance as
      measured by signal to noise plus distortion ratio. Finally, both gradiometer
      designs were compared with standard ECG recording methods and showed less than 1%
      beat detection mismatch employing an open source beat detection algorithm.

PMID- 23008245
TI  - The relevance voxel machine (RVoxM): a self-tuning Bayesian model for informative
      image-based prediction.
AB  - This paper presents the relevance voxel machine (RVoxM), a dedicated Bayesian
      model for making predictions based on medical imaging data. In contrast to the
      generic machine learning algorithms that have often been used for this purpose,
      the method is designed to utilize a small number of spatially clustered sets of
      voxels that are particularly suited for clinical interpretation. RVoxM
      automatically tunes all its free parameters during the training phase, and offers
      the additional advantage of producing probabilistic prediction outcomes. We
      demonstrate RVoxM as a regression model by predicting age from volumetric gray
      matter segmentations, and as a classification model by distinguishing patients
      with Alzheimer's disease from healthy controls using surface-based cortical
      thickness data. Our results indicate that RVoxM yields biologically meaningful
      models, while providing state-of-the-art predictive accuracy.

PMID- 23008246
TI  - A multichannel Markov random field framework for tumor segmentation with an
      application to classification of gene expression-based breast cancer recurrence
      risk.
AB  - We present a methodological framework for multichannel Markov random fields
      (MRFs). We show that conditional independence allows loopy belief propagation to
      solve a multichannel MRF as a single channel MRF. We use conditional mutual
      information to search for features that satisfy conditional independence
      assumptions. Using this framework we incorporate kinetic feature maps derived
      from breast dynamic contrast enhanced magnetic resonance imaging as observation
      channels in MRF for tumor segmentation. Our algorithm based on multichannel MRF
      achieves an receiver operating characteristic area under curve (AUC) of 0.97 for
      tumor segmentation when using a radiologist's manual delineation as ground truth.
      Single channel MRF based on the best feature chosen from the same pool of
      features as used by the multichannel MRF achieved a lower AUC of 0.89. We also
      present a comparison against the well established normalized cuts segmentation
      algorithm along with commonly used approaches for breast tumor segmentation
      including fuzzy C-means (FCM) and the more recent method of running FCM on
      enhancement variance features (FCM-VES). These previous methods give a lower AUC
      of 0.92, 0.88, and 0.60, respectively. Finally, we also investigate the role of
      superior segmentation in feature extraction and tumor characterization.
      Specifically, we examine the effect of improved segmentation on predicting the
      probability of breast cancer recurrence as determined by a validated tumor gene
      expression assay. We demonstrate that an support vector machine classifier
      trained on kinetic statistics extracted from tumors as segmented by our algorithm
      gives a significant improvement in distinguishing between women with high and low
      recurrence risk, giving an AUC of 0.88 as compared to 0.79, 0.76, 0.75, and 0.66
      when using normalized cuts, single channel MRF, FCM, and FCM-VES, respectively,
      for segmentation.

PMID- 23008247
TI  - Persistent brain network homology from the perspective of dendrogram.
AB  - The brain network is usually constructed by estimating the connectivity matrix
      and thresholding it at an arbitrary level. The problem with this standard method
      is that we do not have any generally accepted criteria for determining a proper
      threshold. Thus, we propose a novel multiscale framework that models all brain
      networks generated over every possible threshold. Our approach is based on
      persistent homology and its various representations such as the Rips filtration,
      barcodes, and dendrograms. This new persistent homological framework enables us
      to quantify various persistent topological features at different scales in a
      coherent manner. The barcode is used to quantify and visualize the evolutionary
      changes of topological features such as the Betti numbers over different scales.
      By incorporating additional geometric information to the barcode, we obtain a
      single linkage dendrogram that shows the overall evolution of the network. The
      difference between the two networks is then measured by the Gromov-Hausdorff
      distance over the dendrograms. As an illustration, we modeled and differentiated
      the FDG-PET based functional brain networks of 24 attention-deficit hyperactivity
      disorder children, 26 autism spectrum disorder children, and 11 pediatric control
      subjects.

PMID- 23008248
TI  - A virtual coiling technique for image-based aneurysm models by dynamic path
      planning.
AB  - Computational algorithms modeling the insertion of endovascular devices, such as
      coil or stents, have gained an increasing interest in recent years. This
      scientific enthusiasm is due to the potential impact that these techniques have
      to support clinicians by understanding the intravascular hemodynamics and
      predicting treatment outcomes. In this work, a virtual coiling technique for
      treating image-based aneurysm models is proposed. A dynamic path planning was
      used to mimic the structure and distribution of coils inside aneurysm cavities,
      and to reach high packing densities, which is desirable by clinicians when
      treating with coils. Several tests were done to evaluate the performance on
      idealized and image-based aneurysm models. The proposed technique was validated
      using clinical information of real coiled aneurysms. The virtual coiling
      technique reproduces the macroscopic behavior of inserted coils and properly
      captures the densities, shapes and coil distributions inside aneurysm cavities. A
      practical application was performed by assessing the local hemodynamic after
      coiling using computational fluid dynamics (CFD). Wall shear stress and intra
      aneurysmal velocities were reduced after coiling. Additionally, CFD simulations
      show that coils decrease the amount of contrast entering the aneurysm and
      increase its residence time.

PMID- 23008249
TI  - List-mode PET motion correction using markerless head tracking: proof-of-concept
      with scans of human subject.
AB  - A custom designed markerless tracking system was demonstrated to be applicable
      for positron emission tomography (PET) brain imaging. Precise head motion
      registration is crucial for accurate motion correction (MC) in PET imaging. State
      of-the-art tracking systems applied with PET brain imaging rely on markers
      attached to the patient's head. The marker attachment is the main weakness of
      these systems. A healthy volunteer participating in a cigarette smoking study to
      image dopamine release was scanned twice for 2 h with  (11)C-racolopride on the
      high resolution research tomograph (HRRT) PET scanner. Head motion was
      independently measured, with a commercial marker-based device and the proposed
      vision-based system. A list-mode event-by-event reconstruction algorithm using
      the detected motion was applied. A phantom study with hand-controlled continuous
      random motion was obtained. Motion was time-varying with long drift motions of up
      to 18 mm and regular step-wise motion of 1-6 mm. The evaluated measures were
      significantly better for motion-corrected images compared to no MC. The
      demonstrated system agreed with a commercial integrated system. Motion-corrected
      images were improved in contrast recovery of small structures.

PMID- 23008250
TI  - Two-direction nonlocal model for image denoising.
AB  - Similarities inherent in natural images have been widely exploited for image
      denoising and other applications. In fact, if a cluster of similar image patches
      is rearranged into a matrix, similarities exist both between columns and rows.
      Using the similarities, we present a two-directional nonlocal (TDNL) variational
      model for image denoising. The solution of our model consists of three
      components: one component is a scaled version of the original observed image and
      the other two components are obtained by utilizing the similarities.
      Specifically, by using the similarity between columns, we get a nonlocal-means
      like estimation of the patch with consideration to all similar patches, while the
      weights are not the pairwise similarities but a set of clusterwise coefficients.
      Moreover, by using the similarity between rows, we also get nonlocal
      autoregression-like estimations for the center pixels of the similar patches. The
      TDNL model leads to an alternative minimization algorithm. Experiments indicate
      that the model can perform on par with or better than the state-of-the-art
      denoising methods.

PMID- 23008251
TI  - Non-Lipschitz lp-regularization and box constrained model for image restoration.
AB  - Nonsmooth nonconvex regularization has remarkable advantages for the restoration
      of piecewise constant images. Constrained optimization can improve the image
      restoration using a priori information. In this paper, we study regularized
      nonsmooth nonconvex minimization with box constraints for image restoration. We
      present a computable positive constant  theta for using nonconvex nonsmooth
      regularization, and show that the difference between each pixel and its four
      adjacent neighbors is either 0 or larger than  theta in the recovered image.
      Moreover, we give an explicit form of  theta for the box-constrained image
      restoration model with the non-Lipschitz nonconvex   l(p)-norm   regularization.
      Our theoretical results show that any local minimizer of this imaging restoration
      problem is composed of constant regions surrounded by closed contours and edges.
      Numerical examples are presented to validate the theoretical results, and show
      that the proposed model can recover image restoration results very well.

PMID- 23008252
TI  - Image-difference prediction: from grayscale to color.
AB  - Existing image-difference measures show excellent accuracy in predicting
      distortions, such as lossy compression, noise, and blur. Their performance on
      certain other distortions could be improved; one example of this is gamut
      mapping. This is partly because they either do not interpret chromatic
      information correctly or they ignore it entirely. We present an image-difference
      framework that comprises image normalization, feature extraction, and feature
      combination. Based on this framework, we create image-difference measures by
      selecting specific implementations for each of the steps. Particular emphasis is
      placed on using color information to improve the assessment of gamut-mapped
      images. Our best image-difference measure shows significantly higher prediction
      accuracy on a gamut-mapping dataset than all other evaluated measures.

PMID- 23008253
TI  - Task-specific image partitioning.
AB  - Image partitioning is an important preprocessing step for many of the state-of
      the-art algorithms used for performing high-level computer vision tasks.
      Typically, partitioning is conducted without regard to the task in hand. We
      propose a task-specific image partitioning framework to produce a region-based
      image representation that will lead to a higher task performance than that
      reached using any task-oblivious partitioning framework and existing supervised
      partitioning framework, albeit few in number. The proposed method partitions the
      image by means of correlation clustering, maximizing a linear discriminant
      function defined over a superpixel graph. The parameters of the discriminant
      function that define task-specific similarity/dissimilarity among superpixels are
      estimated based on structured support vector machine (S-SVM) using task-specific
      training data. The S-SVM learning leads to a better generalization ability while
      the construction of the superpixel graph used to define the discriminant function
      allows a rich set of features to be incorporated to improve discriminability and
      robustness. We evaluate the learned task-aware partitioning algorithms on three
      benchmark datasets. Results show that task-aware partitioning leads to better
      labeling performance than the partitioning computed by the state-of-the-art
      general-purpose and supervised partitioning algorithms. We believe that the task
      specific image partitioning paradigm is widely applicable to improving
      performance in high-level image understanding tasks.

PMID- 23008254
TI  - Direct discriminant locality preserving projection with Hammerstein polynomial
      expansion.
AB  - Discriminant locality preserving projection (DLPP) is a linear approach that
      encodes discriminant information into the objective of locality preserving
      projection and improves its classification ability. To enhance the nonlinear
      description ability of DLPP, we can optimize the objective function of DLPP in
      reproducing kernel Hilbert space to form a kernel-based discriminant locality
      preserving projection (KDLPP). However, KDLPP suffers the following problems: 1)
      larger computational burden; 2) no explicit mapping functions in KDLPP, which
      results in more computational burden when projecting a new sample into the low
      dimensional subspace; and 3) KDLPP cannot obtain optimal discriminant vectors,
      which exceedingly optimize the objective of DLPP. To overcome the weaknesses of
      KDLPP, in this paper, a direct discriminant locality preserving projection with
      Hammerstein polynomial expansion (HPDDLPP) is proposed. The proposed HPDDLPP
      directly implements the objective of DLPP in high-dimensional second-order
      Hammerstein polynomial space without matrix inverse, which extracts the optimal
      discriminant vectors for DLPP without larger computational burden. Compared with
      some other related classical methods, experimental results for face and palmprint
      recognition problems indicate the effectiveness of the proposed HPDDLPP.

PMID- 23008255
TI  - Additive white Gaussian noise level estimation in SVD domain for images.
AB  - Accurate estimation of Gaussian noise level is of fundamental interest in a wide
      variety of vision and image processing applications as it is critical to the
      processing techniques that follow. In this paper, a new effective noise level
      estimation method is proposed on the basis of the study of singular values of
      noise-corrupted images. Two novel aspects of this paper address the major
      challenges in noise estimation: 1) the use of the tail of singular values for
      noise estimation to alleviate the influence of the signal on the data basis for
      the noise estimation process and 2) the addition of known noise to estimate the
      content-dependent parameter, so that the proposed scheme is adaptive to visual
      signals, thereby enabling a wider application scope of the proposed scheme. The
      analysis and experiment results demonstrate that the proposed algorithm can
      reliably infer noise levels and show robust behavior over a wide range of visual
      content and noise conditions, and that is outperforms relevant existing methods.

PMID- 23008256
TI  - Unsupervised amplitude and texture classification of SAR images with multinomial
      latent model.
AB  - In this paper, we combine amplitude and texture statistics of the synthetic
      aperture radar images for the purpose of model-based classification. In a finite
      mixture model, we bring together the Nakagami densities to model the class
      amplitudes and a 2-D auto-regressive texture model with  t-distributed regression
      error to model the textures of the classes. A non-stationary multinomial logistic
      latent class label model is used as a mixture density to obtain spatially smooth
      class segments. The classification expectation-maximization algorithm is
      performed to estimate the class parameters and to classify the pixels. We resort
      to integrated classification likelihood criterion to determine the number of
      classes in the model. We present our results on the classification of the land
      covers obtained in both supervised and unsupervised cases processing TerraSAR-X,
      as well as COSMO-SkyMed data.

PMID- 23008257
TI  - Fuzzy C-means clustering with local information and kernel metric for image
      segmentation.
AB  - In this paper, we present an improved fuzzy C-means (FCM) algorithm for image
      segmentation by introducing a tradeoff weighted fuzzy factor and a kernel metric.
      The tradeoff weighted fuzzy factor depends on the space distance of all
      neighboring pixels and their gray-level difference simultaneously. By using this
      factor, the new algorithm can accurately estimate the damping extent of
      neighboring pixels. In order to further enhance its robustness to noise and
      outliers, we introduce a kernel distance measure to its objective function. The
      new algorithm adaptively determines the kernel parameter by using a fast
      bandwidth selection rule based on the distance variance of all data points in the
      collection. Furthermore, the tradeoff weighted fuzzy factor and the kernel
      distance measure are both parameter free. Experimental results on synthetic and
      real images show that the new algorithm is effective and efficient, and is
      relatively independent of this type of noise.

PMID- 23008258
TI  - Nonedge-specific adaptive scheme for highly robust blind motion deblurring of
      natural imagess.
AB  - Blind motion deblurring estimates a sharp image from a motion blurred image
      without the knowledge of the blur kernel. Although significant progress has been
      made on tackling this problem, existing methods, when applied to highly diverse
      natural images, are still far from stable. This paper focuses on the robustness
      of blind motion deblurring methods toward image diversity-a critical problem that
      has been previously neglected for years. We classify the existing methods into
      two schemes and analyze their robustness using an image set consisting of 1.2
      million natural images. The first scheme is edge-specific, as it relies on the
      detection and prediction of large-scale step edges. This scheme is sensitive to
      the diversity of the image edges in natural images. The second scheme is nonedge
      specific and explores various image statistics, such as the prior distributions.
      This scheme is sensitive to statistical variation over different images. Based on
      the analysis, we address the robustness by proposing a novel nonedge-specific
      adaptive scheme (NEAS), which features a new prior that is adaptive to the
      variety of textures in natural images. By comparing the performance of NEAS
      against the existing methods on a very large image set, we demonstrate its
      advance beyond the state-of-the-art.

PMID- 23008259
TI  - Performance evaluation methodology for historical document image binarization.
AB  - Document image binarization is of great importance in the document image analysis
      and recognition pipeline since it affects further stages of the recognition
      process. The evaluation of a binarization method aids in studying its algorithmic
      behavior, as well as verifying its effectiveness, by providing qualitative and
      quantitative indication of its performance. This paper addresses a pixel-based
      binarization evaluation methodology for historical handwritten/machine-printed
      document images. In the proposed evaluation scheme, the recall and precision
      evaluation measures are properly modified using a weighting scheme that
      diminishes any potential evaluation bias. Additional performance metrics of the
      proposed evaluation scheme consist of the percentage rates of broken and missed
      text, false alarms, background noise, character enlargement, and merging. Several
      experiments conducted in comparison with other pixel-based evaluation measures
      demonstrate the validity of the proposed evaluation scheme.

PMID- 23008260
TI  - Video quality pooling adaptive to perceptual distortion severity.
AB  - It is generally recognized that severe video distortions that are transient in
      space and/or time have a large effect on overall perceived video quality. In
      order to understand this phenomena, we study the distribution of spatio
      temporally local quality scores obtained from several video quality assessment
      (VQA) algorithms on videos suffering from compression and lossy transmission over
      communication channels. We propose a content adaptive spatial and temporal
      pooling strategy based on the observed distribution. Our method adaptively
      emphasizes "worst" scores along both the spatial and temporal dimensions of a
      video sequence and also considers the perceptual effect of large-area cohesive
      motion flow such as egomotion. We demonstrate the efficacy of the method by
      testing it using three different VQA algorithms on the LIVE Video Quality
      database and the EPFL-PoliMI video quality database.

PMID- 23008263
TI  - Providing semantic interoperability between clinical care and clinical research
      domains.
AB  - Improving the efficiency with which clinical research studies are conducted can
      lead to faster medication innovation and decreased time to market for new drugs.
      To increase this efficiency, the parties involved in a regulated clinical
      research study, namely, the sponsor, the clinical investigator and the regulatory
      body, each with their own software applications, need to exchange data
      seamlessly. However, currently, the clinical research and the clinical care
      domains are quite disconnected because each use different standards and
      terminology systems. In this article, we describe an initial implementation of
      the Semantic Framework developed within the scope of SALUS project to achieve
      interoperability between the clinical research and the clinical care domains. In
      our Semantic Framework, the core ontology developed for semantic mediation is
      based on the shared conceptual model of both of these domains provided by the
      BRIDG initiative. The core ontology is then aligned with the extracted semantic
      models of the existing clinical care and research standards as well as with the
      ontological representations of the terminology systems to create a model of
      meaning for enabling semantic mediation. Although SALUS is a research and
      development effort rather than a product, the current SALUS knowledge base
      contains around 4.7 million triples representing BRIDG DAM, HL7 CDA model, CDISC
      standards and several terminology ontologies. In order to keep the reasoning
      process within acceptable limits without sacrificing the quality of mediation, we
      took an engineering approach by developing a number of heuristic mechanisms. The
      results indicate that it is possible to build a robust and scalable semantic
      framework with a solid theoretical foundation for achieving interoperability
      between the clinical research and clinical care domains. 

PMID- 23008264
TI  - Automated recovery of the center of rotation in optical projection tomography in
      the presence of scattering.
AB  - Finding the center of rotation is an essential step for accurate three
      dimensional reconstruction in optical projection tomography (OPT). Unfortunately
      current methods are not convenient since they require either prior scanning of a
      reference phantom, small structures of high intensity existing in the specimen,
      or active participation during the centering procedure. To solve these problems
      this paper proposes a fast and automatic center of rotation search method making
      use of parallel programming in graphics processing units (GPUs). Our method is
      based on a two step search approach making use only of those sections of the
      image with high signal to noise ratio. We have tested this method both in non
      scattering ex vivo samples and in in vivo specimens with a considerable
      contribution of scattering such as Drosophila melanogaster pupae, recovering in
      all cases the center of rotation with a precision 1/4 pixel or less. 

PMID- 23008262
TI  - Inducing endoderm differentiation by modulating mechanical properties of soft
      substrates.
AB  - Early embryonic stem cell (ESC) differentiation is marked by the formation of
      three germ layers from which all tissues types arise. Conventionally, ESCs are
      differentiated by altering their chemical microenvironment. Recently however, it
      was established that a mechanical microenvironment can also contribute towards
      cellular phenotype commitment. In this study, we report how the cellular
      mechanical microenvironment of soft substrates affects the differentiation and
      phenotypic commitment of ESCs. Mouse ESCs were cultured in a fibrin hydrogel
      matrix in 2D and 3D cultures. The gelation characteristics of the substrates were
      modulated by systematically altering the fibrinogen concentration and the
      fibrinogen-thrombin crosslinking ratio. Analysis of the ESCs cultured on
      different substrate conditions clearly illustrated the strong influence that
      substrate physical characteristics assert on cellular behaviours. Specifically,
      it was found that ESCs had a higher proliferation rate in gels of lower
      stiffness. Early differentiation events were studied by analyzing the gene and
      protein expression levels of early germ layer markers. Our results revealed that
      lower substrate stiffness elicited stronger upregulation of endoderm related
      genes Sox17, Afp and Hnf4 compared to stiffer substrates. While both 2D and 3D
      cultures showed a similar response, the effects were much stronger in 3D culture.
      These results suggest that physical cues can be used to modulate ESC
      differentiation into clinically relevant tissues such as liver and pancreas.

PMID- 23008265
TI  - Multivariate prediction of subcutaneous glucose concentration in type 1 diabetes
      patients based on support vector regression.
AB  - Data-driven techniques have recently drawn significant interest in the predictive
      modeling of subcutaneous (s.c.) glucose concentration in type 1 diabetes. In this
      study, the s.c. glucose prediction is treated as a multivariate regression
      problem, which is addressed using support vector regression (SVR). The proposed
      method is based on variables concerning: (i) the s.c. glucose profile, (ii) the
      plasma insulin concentration, (iii) the appearance of meal-derived glucose in the
      systemic circulation, and (iv) the energy expenditure during physical activities.
      Six cases corresponding to different combinations of the aforementioned variables
      are used to investigate the influence of the input on the daily glucose
      prediction. The proposed method is evaluated using a dataset of 27 patients in
      free-living conditions. 10-fold cross validation is applied to each dataset
      individually to both optimize and test the SVR model. In the case where all the
      input variables are considered, the average prediction errors are 5.21, 6.03,
      7.14 and 7.62 mg/dl for 15, 30, 60 and 120 min prediction horizons, respectively.
      The results clearly indicate that the availability of multivariable data and
      their effective combination can significantly increase the accuracy of both short
      term and long-term predictions. 

PMID- 23008266
TI  - Control of low-density lipoprotein concentration in the arterial wall by
      proportional drug-encapsulated nanoparticles.
AB  - Atherosclerosis, or hardening of the arteries, is one of the major causes of
      death in humans. High accumulation of Low-Density Lipoprotein (LDL)
      macromolecules within the arterial wall plays a critical role in initiation and
      development of atherosclerotic plaques. This paper proposes a proportional drug
      encapsulated nanoparticle (PDENP) that utilizes a simple piecewise-proportional
      controller to realize swarm feedback control of LDL concentration in the interior
      of the arterial wall. In contrast to the competing strategies on nanorobotics,
      PDENPs carry simpler hardware architecture in order to be more reasonably
      realized technologically as well as to penetrate the interior arterial wall.
      Furthermore, in contrast to the existing targeted DENPs that usually target the
      surface proteins of atherosclerotic plaque, the proposed PDENPs directly sense
      the LDL level in the arterial walls. Hence, they can diagnose abnormal LDL
      accumulation before plaque formation, prevent critical growth of atherosclerotic
      plaques, while considerably reducing the unwanted drug side effects in healthy
      tissue. Simulation results on a well-known mathematical model of the arterial
      wall demonstrate that the proposed approach successfully reduces the LDL level to
      a desired value in the arterial wall of a patient with very high LDL level. Also,
      the mass of the released drug by PDENPs in a healthy wall is 11 times less than
      its corresponding value in an unhealthy wall.

PMID- 23008267
TI  - Regulation of neurite outgrowth mediated by localized phosphorylation of protein
      translational factor eEF2 in growth cones.
AB  - Nerve growth cones contain mRNA and its translational machinery and thereby
      synthesize protein locally. The regulatory mechanisms in the growth cone,
      however, remain largely unknown. We previously found that the calcium entry
      induced increase of phosphorylation of eukaryotic elongation factor-2 (eEF2), a
      key component of mRNA translation, within growth cones showed growth arrest of
      neurites. Because dephosphorylated eEF2 and phosphorylated eEF2 are known to
      promote and inhibit mRNA translation, respectively, the data led to the
      hypothesis that eEF2-mediating mRNA translation may regulate neurite outgrowth.
      Here, we validated the hypothesis by using a chromophore-assisted light
      inactivation (CALI) technique to examine the roles of localized eEF2 and eEF2
      kinase (EF2K), a specific calcium calmodulin-dependent enzyme for eEF2
      phosphorylation, in advancing growth cones of cultured chick dorsal root ganglion
      (DRG) neurons. The phosphorylated eEF2 was weakly distributed in advancing growth
      cones, whereas eEF2 phosphorylation was increased by extracellular adenosine
      triphosphate (ATP)-evoked calcium transient through P2 purinoceptors in growth
      cones and resulted in growth arrest of neurites. The increase of eEF2
      phosphorylation within growth cones by inhibition of protein phosphatase 2A known
      to dephosphorylate eEF2 also showed growth arrest of neurites. CALI of eEF2
      within growth cones resulted in retardation of neurite outgrowth, whereas CALI of
      EF2K enhanced neurite outgrowth temporally. Moreover, CALI of EF2K abolished the
      ATP-induced retardation of neurite outgrowth. These findings suggest that an eEF2
      phosphorylation state localized to the growth cone regulates neurite outgrowth.

PMID- 23008268
TI  - Airborne PM2.5 chemical components and low birth weight in the northeastern and
      mid-Atlantic regions of the United States.
AB  - BACKGROUND: Previous studies on air pollutants and birth outcomes have reported
      inconsistent results. Chemical components of particulate matter <= 2.5 um (PM2.5)
      composition are spatially -heterogeneous, which might contribute to discrepancies
      across PM2.5 studies. OBJECTIVES: We explored whether birth weight at term is
      affected by PM2.5, PM10 (PM <= 10 um), and gaseous pollutants. METHODS: We
      calculated exposures during gestation and each trimester for PM2.5 chemical
      components, PM10, PM2.5, carbon monoxide, nitrogen dioxide, ozone, and sulfur
      dioxide for births in 2000-2007 for states in the northeastern and mid-Atlantic
      United States. Associations between exposures and risk of low birth weight (LBW)
      were adjusted by family and individual characteristics and region. Interaction
      terms were used to investigate whether risk differs by race or sex. RESULTS:
      Several PM2.5 chemical components were associated with LBW. Risk increased 4.9%
      (95% CI: 3.4, 6.5%), 4.7% (3.2, 6.2%), 5.7% (2.7, 8.8%), and 5.0% (3.1, 7.0%) per
      interquartile range increase of PM2.5 aluminum, elemental carbon, nickel, and
      titanium, respectively. Other PM2.5 chemical components and gaseous pollutants
      showed associations, but were not statistically significant in multipollutant
      models. The trimester associated with the highest relative risk differed among
      pollutants. Effect estimates for PM2.5 elemental carbon and nickel were higher
      for infants of white mothers than for those of African-American mothers, and for
      males than females. CONCLUSIONS: Most exposure levels in our study area were in
      compliance with U.S. Environmental Protection Agency air pollution standards;
      however, we identified associations between PM2.5 components and LBW. Findings
      suggest that some PM2.5 components may be more harmful than others, and that some
      groups may be particularly susceptible.

PMID- 23008269
TI  - Regulation of ephrin-A expression in compressed retinocollicular maps.
AB  - Retinotopic maps can undergo compression and expansion in response to changes in
      target size, but the mechanism underlying this compensatory process has remained
      a mystery. The discovery of ephrins as molecular mediators of Sperry's
      chemoaffinity process allows a mechanistic approach to this important issue. In
      Syrian hamsters, neonatal, partial (PT) ablation of posterior superior colliculus
      (SC) leads to compression of the retinotopic map, independent of neural activity.
      Graded, repulsive EphA receptor/ephrin-A ligand interactions direct the formation
      of the retinocollicular map, but whether ephrins might also be involved in map
      compression is unknown. To examine whether map compression might be directed by
      changes in the ephrin expression pattern, we compared ephrin-A2 and ephrin-A5
      mRNA expression between normal SC and PT SC using in situ hybridization and
      quantitative real-time PCR. We found that ephrin-A ligand expression in the
      compressed maps was low anteriorly and high posteriorly, as in normal animals.
      Consistent with our hypothesis, the steepness of the ephrin gradient increased in
      the lesioned colliculi. Interestingly, overall levels of ephrin-A2 and -A5
      expression declined immediately after neonatal target damage, perhaps promoting
      axon outgrowth. These data establish a correlation between changes in ephrin-A
      gradients and map compression, and suggest that ephrin-A expression gradients may
      be regulated by target size. This in turn could lead to compression of the
      retinocollicular map onto the reduced target. These findings have important
      implications for mechanisms of recovery from traumatic brain injury.

PMID- 23008270
TI  - Near-roadway pollution and childhood asthma: implications for developing "win
      win" compact urban development and clean vehicle strategies.
AB  - BACKGROUND: The emerging consensus that exposure to near-roadway traffic-related
      pollution causes asthma has implications for compact urban development policies
      designed to reduce driving and greenhouse gases. OBJECTIVES: We estimated the
      current burden of childhood asthma-related disease attributable to near-roadway
      and regional air pollution in Los Angeles County (LAC) and the potential health
      impact of regional pollution reduction associated with changes in population
      along major traffic corridors. METHODS: The burden of asthma attributable to the
      dual effects of near-roadway and regional air pollution was estimated, using
      nitrogen dioxide and ozone as markers of urban combustion-related and secondary
      oxidant pollution, respectively. We also estimated the impact of alternative
      scenarios that assumed a 20% reduction in regional pollution in combination with
      a 3.6% reduction or 3.6% increase in the proportion of the total population
      living near major roads, a proxy for near-roadway exposure. RESULTS: We estimated
      that 27,100 cases of childhood asthma (8% of total) in LAC were at least partly
      attributable to pollution associated with residential location within 75 m of a
      major road. As a result, a substantial proportion of asthma-related morbidity is
      a consequence of near-roadway pollution, even if symptoms are triggered by other
      factors. Benefits resulting from a 20% regional pollution reduction varied
      markedly depending on the associated change in near-roadway proximity.
      CONCLUSIONS: Our findings suggest that there are large and previously
      unappreciated public health consequences of air pollution in LAC and probably in
      other metropolitan areas with dense traffic corridors. To maximize health
      benefits, compact urban development strategies should be coupled with policies to
      reduce near-roadway pollution exposure.

PMID- 23008271
TI  - Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders: an
      exploratory study.
AB  - Evidence suggests that some developmental disorders, such as autism spectrum
      disorders (ASDs), are caused by errors in brain plasticity. Given the important
      role of matrix metalloproteinases (MMPs) and neurotrophins (NTs) in
      neuroplasticity, amniotic fluid samples for 331 ASD cases and 698 frequency
      matched controls were analyzed for levels of MMP-9, brain-derived neurotrophic
      factor, NT-4 and transforming growth factor-beta utilizing a Danish historic
      birth cohort and Danish nationwide health registers. Laboratory measurements were
      performed using an in-house multiplex sandwich immunoassay Luminex xMAP method,
      and measurements were analyzed using tobit and logistic regression. Results
      showed elevated levels of MMP-9 in ASD cases compared with controls (crude and
      adjusted tobit regression P-values: 0.01 and 0.06). Our results highlight the
      importance of exploring the biologic impact of MMP-9 and potential therapeutic
      roles of its inhibitors in ASD and may indicate that neuroplastic impairments in
      ASD may present during pregnancy.

PMID- 23008272
TI  - Is CO2 an indoor pollutant? Direct effects of low-to-moderate CO2 concentrations
      on human decision-making performance.
AB  - BACKGROUND: Associations of higher indoor carbon dioxide (CO2) concentrations
      with impaired work performance, increased health symptoms, and poorer perceived
      air quality have been attributed to correlation of indoor CO2 with concentrations
      of other indoor air pollutants that are also influenced by rates of outdoor-air
      ventilation. OBJECTIVES: We assessed direct effects of increased CO2, within the
      range of indoor concentrations, on decision making. METHODS: Twenty-two
      participants were exposed to CO2 at 600, 1,000, and 2,500 ppm in an office-like
      chamber, in six groups. Each group was exposed to these conditions in three 2.5
      hr sessions, all on 1 day, with exposure order balanced across groups. At 600
      ppm, CO2 came from outdoor air and participants' respiration. Higher
      concentrations were achieved by injecting ultrapure CO2. Ventilation rate and
      temperature were constant. Under each condition, participants completed a
      computer-based test of decision-making performance as well as questionnaires on
      health symptoms and perceived air quality. Participants and the person
      administering the decision-making test were blinded to CO2 level. Data were
      analyzed with analysis of variance models. RESULTS: Relative to 600 ppm, at 1,000
      ppm CO2, moderate and statistically significant decrements occurred in six of
      nine scales of decision-making performance. At 2,500 ppm, large and statistically
      significant reductions occurred in seven scales of decision-making performance
      (raw score ratios, 0.06-0.56), but performance on the focused activity scale
      increased. CONCLUSIONS: Direct adverse effects of CO2 on human performance may be
      economically important and may limit energy-saving reductions in outdoor air
      ventilation per person in buildings. Confirmation of these findings is needed.

PMID- 23008273
TI  - Histiocytic sarcoma in the bronchoalveolar lavage fluid.

PMID- 23008275
TI  - Deciduoid mesothelioma: cytologic presentation and diagnostic pitfalls.
AB  - We report two cases of malignant deciduoid mesothelioma (MDM), a very rare
      variant of malignant mesothelioma (MM). Case 1: An 18-year-old male with no
      history of asbestos exposure presented with worsening abdominal pain, anorexia,
      and vomiting after a motor vehicle accident. A CT scan showed small amount of
      ascites and abdominal mass. An exploratory laparotomy revealed multiple yellow
      tan, firm nodules on the peritoneum and omentum. He received palliative treatment
      and died 5 months after the diagnosis. Case 2: A 64-year-old female with history
      of asbestos exposure initially presented with abdominal distension. CT scan
      showed abdominal mass with a large amount of ascites. A diagnostic laparoscopy
      revealed multiple peritoneal nodules. She underwent several regimens of
      chemotherapy over a period of 69 months and is still alive to date. In both
      cases, features of mesothelial origin were subtle and the smears showed
      predominantly single cells with marked nuclear atypia. The second case also
      contained few two-dimensional loose cell clusters with scalloped or hobnail
      borders. The clusters often exhibited a pseudoacinar structure surrounding a
      globular extracellular material. Groups of three to four cells often formed
      doublets and triplets with cell-to-cell windows. Our results show that MDM may
      not present with the traditional cytological features described in MM and can
      manifest with more nuclear pleomorphism resulting in erroneous diagnosis.
      Recognition of the subtle mesothelial features along with the appropriate
      ancillary tests is essential for accurate diagnosis.

PMID- 23008274
TI  - Prenatal methylmercury, postnatal lead exposure, and evidence of attention
      deficit/hyperactivity disorder among Inuit children in Arctic Quebec.
AB  - BACKGROUND: Prenatal exposure to methylmercury (MeHg) and polychlorinated
      biphenyls (PCBs) has been associated with impaired performance on attention tasks
      in previous studies, but the extent to which these cognitive deficits translate
      into behavioral problems in the classroom and attention deficit/hyperactivity
      disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has
      been associated with ADHD and disruptive behaviors in several studies.
      OBJECTIVES: In this study we examined the relation of developmental exposure to
      MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed
      through their traditional diet. METHODS: In a prospective longitudinal study
      conducted in the Canadian Arctic, exposure to contaminants was measured at birth
      and at school age. An assessment of child behavior (n = 279; mean age = 11.3
      years) was obtained from the child's classroom teacher on the Teacher Report Form
      (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders
      Rating Scale (DBD). RESULTS: Cord blood mercury concentrations were associated
      with higher TRF symptom scores for attention problems and DBD scores consistent
      with ADHD. Current blood Pb concentrations were associated with higher TRF
      symptom scores for externalizing problems and with symptoms of ADHD (hyperactive
      impulsive type) based on the DBD. CONCLUSIONS: To our knowledge, this study is
      the first to identify an association between prenatal MeHg and ADHD
      symptomatology in childhood and the first to replicate previously reported
      associations between low-level childhood Pb exposure and ADHD in a population
      exposed to Pb primarily from dietary sources.

PMID- 23008276
TI  - Rice consumption and urinary arsenic concentrations in U.S. children.
AB  - BACKGROUND: In adult populations, emerging evidence indicates that humans are
      exposed to arsenic by ingestion of contaminated foods such as rice, grains, and
      juice; yet little is known about arsenic exposure among children. OBJECTIVES: Our
      goal was to determine whether rice consumption contributes to arsenic exposure in
      U.S. children. METHODS: We used data from the nationally representative National
      Health and Nutrition Examination Survey (NHANES) to examine the relationship
      between rice consumption (measured in 0.25 cups of cooked rice per day) over a 24
      hr period and subsequent urinary arsenic concentration among the 2,323 children
      (6-17 years of age) who participated in NHANES from 2003 to 2008. We examined
      total urinary arsenic (excluding arsenobetaine and arsenocholine) and
      dimethylarsinic acid (DMA) concentrations overall and by age group: 6-11 years
      and 12-17 years. RESULTS: The median [interquartile range (IQR)] total urinary
      arsenic concentration among children who reported consuming rice was 8.9 MUg/L
      (IQR: 5.3-15.6) compared with 5.5 MUg/L (IQR: 3.1-8.4) among those who did not
      consume rice. After adjusting for potentially confounding factors, and
      restricting the study to participants who did not consume seafood in the
      preceding 24 hr, total urinary arsenic concentration increased 14.2% (95%
      confidence interval: 11.3, 17.1%) with each 0.25 cup increase in cooked rice
      consumption. CONCLUSIONS: Our study suggests that rice consumption is a potential
      source of arsenic exposure in U.S. children.

PMID- 23008277
TI  - Solid pseudopapillary tumor of the pancreas: 'experiences' and 'lessons' at a
      tertiary-care oncology center.
AB  - Solid pseudopapillary tumor of the pancreas (SPT) is a rare and fascinating
      entity of elusive histogenesis and unpredictable biology. It has a peculiar
      proclivity to afflict young females and involve the pancreatic body-tail region.
      Cytology diagnosis of these rare neoplasms remains a challenge. We analyzed the
      cytology features of all SPT cases diagnosed on fine needle aspiration cytology
      (FNAC) from 2003 to 2009 along with their histopathology slides. Nineteen
      consecutive cases were diagnosed as SPT on FNAC. Fifteen out of nineteen cases
      were confirmed as true SPT on histopathology. Amongst the true SPT, all except
      one occurred in females. Age ranged from 14 to 50 years. Pseudopapillae bearing
      stout branches terminating in bulbous tips and enclosing transgressing vessels,
      separated from a collar of tumor cells by a clear zone of myxohyaline coat were
      pathognomonic of SPT. Singly dispersed monomorphic tumor cells with bland
      chromatin formed the second diagnostic component of SPT. Nuclear grooves and
      hyaline globules were in addition helpful in segregating SPT from its close
      differentials. In four cases diagnosed as SPT on FNAC, histopathology revealed a
      different final diagnosis (one case each of paraganglioma, extragastrointestinal
      stromal tumor, metastatic papillary renal cell carcinoma and inflammatory
      myofibroblastic tumor). Conversely, one case of SPT had been erroneously
      diagnosed as neuroendocrine tumor on FNAC. Six cases (40%) developed metastasis;
      commonest site being liver. In conclusion, cytology in conjunction with clinico
      radiologic findings plays a key role in making a correct diagnosis. Awareness of
      unique cytomorphological features is important in distinguishing this tumor from
      its diverse mimics.

PMID- 23008278
TI  - Prioritizing chemicals and data requirements for screening-level exposure and
      risk assessment.
AB  - BACKGROUND: Scientists and regulatory agencies strive to identify chemicals that
      may cause harmful effects to humans and the environment; however, prioritization
      is challenging because of the large number of chemicals requiring evaluation and
      limited data and resources. OBJECTIVES: We aimed to prioritize chemicals for
      exposure and exposure potential and obtain a quantitative perspective on research
      needs to better address uncertainty in screening assessments. METHODS: We used a
      multimedia mass balance model to prioritize > 12,000 organic chemicals using four
      far-field human exposure metrics. The propagation of variance (uncertainty) in
      key chemical information used as model input for calculating exposure metrics was
      quantified. RESULTS: Modeled human concentrations and intake rates span
      approximately 17 and 15 orders of magnitude, respectively. Estimates of exposure
      potential using human concentrations and a unit emission rate span approximately
      13 orders of magnitude, and intake fractions span 7 orders of magnitude. The
      actual chemical emission rate contributes the greatest variance (uncertainty) in
      exposure estimates. The human biotransformation half-life is the second greatest
      source of uncertainty in estimated concentrations. In general, biotransformation
      and biodegradation half-lives are greater sources of uncertainty in modeled
      exposure and exposure potential than chemical partition coefficients.
      CONCLUSIONS: Mechanistic exposure modeling is suitable for screening and
      prioritizing large numbers of chemicals. By including uncertainty analysis and
      uncertainty in chemical information in the exposure estimates, these methods can
      help identify and address the important sources of uncertainty in human exposure
      and risk assessment in a systematic manner.

PMID- 23008279
TI  - "Intermediate filament buttons" in a fine-needle aspirate of Merkel cell
      carcinoma.

PMID- 23008281
TI  - Health and wellness programming in faith-based organizations: a description of a
      nationwide sample.
AB  - INTRODUCTION: Most of the U.S. population is affiliated with faith-based
      organizations (FBOs) and regularly attends services. Health and wellness
      activities (HWA) delivered through FBOs have great potential for reach, but the
      number of FBOs offering health programs and the characteristics of these programs
      are currently unknown. The purpose of this study was to better understand rates,
      characteristics, and factors influencing faith-based HWA across the United
      States. METHOD: Faith leaders (N = 844) completed an online survey assessing
      faith leader demographics and health, FBO demographics (e.g., denomination, size,
      location, diversity), and details of HWA within their FBO. RESULTS: Respondents
      were primarily White (93%), male (72%), middle-aged (53.2 +/- 12.1 years), and
      affiliated with Methodist (42.5%) or Lutheran (20.2%) denominations. Although
      most faith leaders report meeting physical activity recommendations (56.5%), most
      were overweight/obese (77.4%), did not meet fruit and vegetable recommendations
      (65.9%), and had been diagnosed with 1.25 +/- 1.36 chronic diseases. Respondents
      reported offering 4.8 +/- 3 HWA within their FBO over the past 12 months. Most
      common HWA included clubs/teams related to physical activity (54.8%), individual
      level health counseling (54%), and providing health/wellness pamphlets. Leaders
      cited a lack of lay leadership (48.1%) and financial resources for staff time
      (47.8%) as the most common barriers to HWA. An increase in interest/awareness in
      health topics from FBO members was the most common facilitator for HWA (66.5%).
      CONCLUSION: Although faith-based HWA are prevalent nationally, types of HWA and
      the factors influencing HWA are dependent on FBO characteristics. Future faith
      based interventions should consider existing capabilities and moderating factors
      for HWA.

PMID- 23008280
TI  - Competitive androgen receptor antagonism as a factor determining the
      predictability of cumulative antiandrogenic effects of widely used pesticides.
AB  - BACKGROUND: Many pesticides in current use have recently been revealed as in
      vitro androgen receptor (AR) antagonists, but information about their combined
      effects is lacking. OBJECTIVE: We investigated the combined effects and the
      competitive AR antagonism of pesticide mixtures. METHODS: We used the MDA-kb2
      assay to test a combination of eight AR antagonists that did not also possess AR
      agonist properties ("pure" antagonists; 8 mix: fludioxonil, fenhexamid, ortho
      phenylphenol, imazalil, tebuconazole, dimethomorph, methiocarb, pirimiphos
      methyl), a combination of five AR antagonists that also showed agonist activity
      (5 mix: cyprodinil, pyrimethanil, vinclozolin, chlorpropham, linuron), and all
      pesticides combined (13 mix). We used concentration addition (CA) and independent
      action (IA) to formulate additivity expectations, and Schild plot analyses to
      investigate competitive AR antagonism. RESULTS: A good agreement between the
      effects of the mixture of eight "pure" AR antagonists and the responses predicted
      by CA was observed. Schild plot analysis revealed that the 8 mix acted by
      competitive AR antagonism. However, the observed responses of the 5 mix and the
      13 mix fell within the "prediction window" boundaries defined by the predicted
      regression curves of CA and IA. Schild plot analysis with these mixtures yielded
      anomalous responses incompatible with competitive receptor antagonism.
      CONCLUSIONS: A mixture of widely used pesticides can, in a predictable manner,
      produce combined AR antagonist effects that exceed the responses elicited by the
      most potent component alone. Inasmuch as large populations are regularly exposed
      to mixtures of antiandrogenic pesticides, our results underline the need for
      considering combination effects for these substances in regulatory practice.

PMID- 23008282
TI  - Building a business case: mining your own business.

PMID- 23008283
TI  - Cutaneous cryptococcosis in solid organ transplant recipients: epidemiological,
      clinical, diagnostic and therapeutic features.
AB  - Data on post-graft cutaneous cryptococcosis (CC) are rare. The objective was to
      delineate the epidemiological, clinical, diagnostic, therapeutic features of CC
      in organ transplant recipients. We compared cases from a cohort of 3,670
      transplanted adults with cases from a regional cryptococcosis registry including
      122 patients. Four CC were diagnosed in the transplanted cohort (10/00)
      corresponding in the regional registry to 33% of the 12 cases of cryptococcosis
      after transplantation, while among the 110 non-grafted patients, only five
      cryptococcosis were cutaneous (4%). CC appeared as a single (3 patients) ulcer or
      nodule over 1cm in size in an uncovered body zone, on average 13 months post
      graft. 3 patients had concomitant opportunistic infections or a recent increase
      in their immunosuppression. All CC after transplantation were localized
      exclusively to the skin, raising the question of the mode of contamination
      (through the skin or the lungs). Evidence of dissemination is difficult because
      of the poor sensitivity of diagnostic tests. Fluconazole was the treatment of
      choice in association with immunosuppressive treatment tapering.

PMID- 23008285
TI  - Cell cycle regulator Cdkn1c (p57/KIP2) shows distinct expression in epidermal
      differentiation.

PMID- 23008287
TI  - Cancer survivorship care: don't let the perfect be the enemy of the good.
AB  - It has now been more than 5 years since the Institute of Medicine (IOM) laid out
      its bold vision of comprehensive survivorship care. Although there is clearly
      more attention paid to this phase of the cancer journey than previously,
      implementation of the IOM recommendations has proved difficult. In this article,
      we review some of the challenges to providing survivorship care and discuss
      efforts to prioritize the most essential elements.

PMID- 23008288
TI  - Association between circulating tumor cells and prognosis in patients with stage
      III melanoma with sentinel lymph node metastasis in a phase III international
      multicenter trial.
AB  - PURPOSE: The outcomes of patients with melanoma who have sentinel lymph node
      (SLN) metastases can be highly variable, which has precluded establishment of
      consensus regarding treatment of the group. The detection of high-risk patients
      from this clinical setting may be helpful for determination of both prognosis and
      management. We report the utility of multimarker reverse-transcriptase
      quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor
      cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase
      III, international, multicenter clinical trial. PATIENTS AND METHODS: Blood
      specimens were collected from patients with melanoma (n = 331) who were
      clinically disease-free after complete lymphadenectomy (CLND) before entering
      onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guerin (BCG)
      versus BCG placebo trial from 30 melanoma centers (United States and
      international). Blood was assessed using a verified multimarker RT-qPCR assay
      (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression
      analyses were used to evaluate the prognostic significance of CTC status for
      disease recurrence and melanoma-specific survival (MSS). RESULTS: Individual CTC
      biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC
      status (zero to one positive biomarkers v two or more positive biomarkers) with
      known clinical or pathologic prognostic variables. However, two or more positive
      biomarkers was significantly associated with worse distant metastasis disease
      free survival (hazard ratio [HR] = 2.13, P = .009) and reduced recurrence-free
      survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable
      analysis. CONCLUSION: CTC biomarker status is a prognostic factor for recurrence
      free survival, distant metastasis disease-free survival, and MSS after CLND in
      patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be
      useful in discriminating patients who may benefit from aggressive adjuvant
      therapy or stratifying patients for adjuvant clinical trials.

PMID- 23008290
TI  - What goes around comes around? Wernicke encephalopathy and the nationwide
      shortage of intravenous multivitamins revisited.

PMID- 23008291
TI  - Nomogram predicting long-term survival after d2 gastrectomy for gastric cancer.
AB  - PURPOSE: The aim of this study was to combine clinicopathologic variables
      associated with overall survival after gastric resection with D2 lymphadenectomy
      (D2 gastrectomy) for gastric cancer into a prediction nomogram. PATIENTS AND
      METHODS: We retrospectively analyzed 7,954 patients who underwent D2 gastrectomy
      for gastric cancer at Seoul National University Hospital (SNUH) in Seoul, Korea.
      Two thirds of the patients were randomly assigned to the training set (n =
      5,300), and one third were assigned to the validation set (n = 2,654).
      Multivariate analysis by Cox proportional hazards regression was performed using
      the training set, and the nomogram was constructed. Discrimination and
      calibration were performed using the SNUH validation set. Additional external
      validation was performed using the data set (n = 2,500) from Cancer Institute
      Ariake Hospital (CIAH) in Tokyo, Japan. RESULTS: The multivariate Cox model
      identified age at diagnosis, sex, location, depth of invasion, number of
      metastatic lymph nodes, and number of examined lymph nodes as covariates
      associated with survival. In the SNUH validation set, the nomogram exhibited
      superior discrimination power compared with the seventh American Joint Committee
      on Cancer TNM classification (Harrell's C-index, 0.78 v 0.69, respectively; P <
      .001). Calibration of the nomogram predicted survival corresponding closely with
      the actual survival. In the CIAH validation set, discrimination was good (C
      index, 0.79), and the predicted survival was within a 10% margin of ideal
      nomogram. CONCLUSION: We developed a nomogram predicting 5- and 10-year overall
      survival after D2 gastrectomy for gastric cancer. Validation using the SNUH and
      CIAH data sets revealed good discrimination and calibration, suggesting good
      clinical utility. The nomogram improved individualized predictions of survival.

PMID- 23008289
TI  - Resistance and escape from antiangiogenesis therapy: clinical implications and
      future strategies.
AB  - Angiogenesis has long been considered an important target for cancer therapy.
      Initial efforts have primarily focused on targeting of endothelial and tumor
      derived vascular endothelial growth factor signaling. As evidence emerges that
      angiogenesis has significant mechanistic complexity, therapeutic resistance and
      escape have become practical limitations to drug development. Here, we review the
      mechanisms by which dynamic changes occur in the tumor microenvironment in
      response to antiangiogenic therapy, leading to drug resistance. These mechanisms
      include direct selection of clonal cell populations with the capacity to rapidly
      upregulate alternative proangiogenic pathways, increased invasive capacity, and
      intrinsic resistance to hypoxia. The implications of normalization of vasculature
      with subsequently improved vascular function as a result of antiangiogenic
      therapy are explored, as are the implications of the ability to incorporate and
      co-opt otherwise normal vasculature. Finally, we consider the extent to which a
      better understanding of the biology of hypoxia and reoxygenation, as well as the
      depth and breadth of systems invested in angiogenesis, may offer putative
      biomarkers and novel therapeutic targets. Insights gained through this work may
      offer solutions for personalizing antiangiogenesis approaches and improving the
      outcome of patients with cancer.

PMID- 23008292
TI  - Short-course radiation versus long-course chemoradiation for rectal cancer:
      making progress.

PMID- 23008293
TI  - Second malignant neoplasms: assessment and strategies for risk reduction.
AB  - Improvements in early detection, supportive care, and treatment have resulted in
      an increasing number of cancer survivors, with a current 5-year relative survival
      rate for all cancers combined of approximately 66.1%. For some patients, these
      survival advances have been offset by the long-term late effects of cancer and
      its treatment, with second malignant neoplasms (SMNs) comprising one of the most
      potentially life-threatening sequelae. The number of patients with SMNs is
      growing, with new SMNs now representing about one in six of all cancers reported
      to the National Cancer Institute's Surveillance, Epidemiology, and End Results
      (SEER) Program. SMNs reflect not only the late effects of therapy but also the
      influence of shared etiologic factors (in particular, tobacco and excessive
      alcohol intake), genetic susceptibility, environmental exposures, host effects,
      and combinations of factors, including gene-environment interactions. For
      selected SMNs, risk is also modified by age at exposure and attained age. SMNs
      can be categorized into three major groups according to the predominant etiologic
      factor(s): (1) treatment-related, (2) syndromic, and (3) those due to shared
      etiologic exposures, although the nonexclusivity of these groups should be
      underscored. Here we provide an overview of SMNs in survivors of adult-onset
      cancer, summarizing the current, albeit limited, clinical evidence with regard to
      screening and prevention, with a focus on the provision of guidance for health
      care providers. The growing number of patients with second (and higher-order)
      cancers mandates that we also further probe etiologic influences and genetic
      variants that heighten risk, and that we better define high-risk groups for
      targeted preventive and interventional clinical strategies.

PMID- 23008294
TI  - Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era:
      results of an F2-study database.
AB  - PURPOSE: Patients with follicular lymphoma (FL) registered in the F2-study and
      initially managed without treatment were analyzed to describe the presentation
      and outcome of a watch and wait (W&W) strategy in the rituximab era, to identify
      parameters for initiating treatment, and to evaluate whether initial W&W could
      have deleterious effects on treatment efficacy after progression or relapse.
      PATIENTS AND METHODS: Between 2003 and 2005, 120 patients selected from the 1,093
      treatment-naive patients with FL in the F2-study cohort were initially managed
      expectantly (W&W), and 107 patients were assessed. Most of these patients (80%)
      had disseminated disease with a low tumor burden according to Groupe d'Etudes des
      Lymphomes Folliculaires criteria. RESULTS: After a median follow-up of 64 months,
      treatment was initiated in 54 patients (50%), with a median delay of 55 months
      for the entire cohort. In a univariate analysis, involvement of more than four
      nodal areas (hazard ratio [HR], 2.26) and serum albumin less than 3.5 g/dL (HR,
      3.51) were predictive of a shorter time to lymphoma treatment initiation. In a
      multivariate analysis, only involvement of more than four nodal areas remained
      significant (HR, 2.32). The 4-year freedom from treatment failure (FFTF) rate of
      W&W patients (79%; 95% CI, 69% to 85%) was not inferior to that of a subgroup of
      242 patients from the F2-study cohort with good prognosis characteristics who
      were initially treated with a rituximab-based regimen (69%; 95% CI, 61% to 76%; P
      = .103). CONCLUSION: In the rituximab era, patients with FL in a selected
      prognostically favorable group can still be managed with W&W. W&W does not seem
      to have detrimental effects on FFTF and overall survival rates after treatment.

PMID- 23008295
TI  - Estrogen plus progestin and colorectal cancer incidence and mortality.
AB  - PURPOSE: During the intervention phase in the Women's Health Initiative (WHI)
      clinical trial, use of estrogen plus progestin reduced the colorectal cancer
      diagnosis rate, but the cancers were found at a substantially higher stage. To
      assess the clinical relevance of the findings, analyses of the influence of
      combined hormone therapy on colorectal cancer incidence and colorectal cancer
      mortality were conducted after extended follow-up. PATIENTS AND METHODS: The WHI
      study was a randomized, double-blind, placebo-controlled clinical trial involving
      16,608 postmenopausal women with an intact uterus who were randomly assigned to
      daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate
      (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates
      and colorectal cancer mortality were assessed. RESULTS: After a mean of 5.6 years
      (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1
      years) of total follow-up, fewer colorectal cancers were diagnosed in the
      combined hormone therapy group compared with the placebo group (diagnoses/year,
      0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel
      screening examinations were comparable between groups throughout. Cancers in the
      combined hormone therapy group more commonly had positive lymph nodes (50.5% v
      28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P
      = .003). Although not statistically significant, there was a higher number of
      colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths;
      0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320). CONCLUSION: The
      findings, suggestive of diagnostic delay, do not support a clinically meaningful
      benefit for combined hormone therapy on colorectal cancer.

PMID- 23008297
TI  - Late cardiac effects of cancer treatment.
AB  - Cardiac toxicities from cancer therapy can become evident many years after
      treatment, and these late cardiac effects can have a profound impact on cancer
      survivors. There are a myriad of potential cardiovascular complications from
      cancer therapy, but these can be grouped into three main categories. First,
      vascular conditions including atherosclerosis, thrombosis, and hypertension
      predominate. Second, cardiac structural problems, especially valvular
      degeneration, can have a dramatic impact long term. Lastly, and most importantly,
      cardiac dysfunction and heart failure are potentially common late cardiac effects
      and can certainly be prevented or detected early during active cancer therapy to
      result in optimal outcomes. Future research on late cardiac effects in cancer
      survivors needs to include advanced cardiac imaging techniques, novel cardiac
      biomarkers, and genetic determinants of response to cancer treatment.

PMID- 23008296
TI  - Delivering care to long-term adult survivors of hematopoietic cell
      transplantation.
AB  - This review highlights long-term and late consequences of hematopoietic cell
      transplantation (HCT) as well as strategies to manage or prevent complications
      that are more prevalent after HCT than most other cancer treatments. Chronic
      graft-versus-host disease stands out as a unique late effect of allogeneic HCT
      that is not seen after other types of cancer treatment. However, many other
      complications seen after solid tumor treatments are also common after HCT,
      including infections, second cancers, bone loss, and cardiovascular, pulmonary,
      renal, and endocrine dysfunction. Symptoms and syndromes that are reported after
      HCT include sexual dysfunction, cognitive problems, fatigue, insomnia,
      musculoskeletal symptoms, emotional distress, anger, and depression. Addressing
      these complex potential or actual complications requires diligent routine health
      care to intervene early or, when possible, to prevent late complications. To
      accomplish early detection and prevention of life-threatening complications, HCT
      survivors should undergo an annual comprehensive physical examination that
      includes screening for functional and psychosocial consequences of treatment and
      encouraging healthy lifestyle behaviors. Clinicians can link survivors to
      numerous online, print, and video resources to help them advocate for their
      health needs.

PMID- 23008298
TI  - How much of a good thing? What duration for interferon alfa-2b adjuvant therapy?

PMID- 23008299
TI  - Cancer-related lymphedema risk factors, diagnosis, treatment, and impact: a
      review.
AB  - PURPOSE Cancer-related lymphedema (LE) is an incurable condition associated with
      lymph-involved cancer treatments and is an increasing health, quality of life
      (QOL), and cost burden on a growing cancer survivor population. This review
      examines the evidence for causes, risk, prevention, diagnosis, treatment, and
      impact of this largely unexamined survivorship concern.   METHODS PubMed and
      Medline were searched for cancer-related LE literature published since 1990 in
      English. The resulting references (N = 726) were evaluated for strength of
      design, methods, sample size, and recent publication and sorted into categories
      (ie, causes/prevention, diagnosis, treatment, and QOL). Sixty studies were
      included.  Results Exercise and physical activity and sentinel lymph node biopsy
      reduce risk, and overweight and obesity increase risk. Evidence that
      physiotherapy reduces risk and that lymph node status and number of malignant
      nodes increase risk is less strong. Perometry and bioimpedence emerged as
      attractive diagnostic technologies, replacing the use of water displacement in
      clinical practice. Swelling can also be assessed by measuring arm circumference
      and relying on self-report. Symptoms can be managed, not cured, with complex
      physical therapy, low-level laser therapy, pharmacotherapy, and surgery. Sequelae
      of LE negatively affect physical and mental QOL and range in severity. However,
      the majority of reviewed studies involved patients with breast cancer; therefore,
      results may not be applicable to all cancers.   CONCLUSION Research into causes,
      prevention, and effect on QOL of LE and information on LE in cancers other than
      breast is needed. Consensus on definitions and measurement, increased patient and
      provider awareness of signs and symptoms, and proper and prompt treatment/access,
      including psychosocial support, are needed to better understand, prevent, and
      treat LE.

PMID- 23008300
TI  - Long-term results of the randomized phase III trial EORTC 18991 of adjuvant
      therapy with pegylated interferon alfa-2b versus observation in resected stage
      III melanoma.
AB  - PURPOSE: Adjuvant pegylated interferon alfa-2b (PEG-IFN-alpha-2b) was approved
      for treatment of resected stage III melanoma in 2011. Here, we present long-term
      follow-up results of this pivotal trial. PATIENTS AND METHODS: In all, 1,256
      patients with resected stage III melanoma were randomly assigned to observation
      (n = 629) or PEG-IFN-alpha-2b (n = 627) for an intended duration of 5 years.
      Stratification factors were microscopic (N1) versus macroscopic (N2) nodal
      involvement, number of positive nodes, ulceration and tumor thickness, sex, and
      center. Recurrence-free survival (RFS; primary end point), distant metastasis
      free survival (DMFS), and overall survival (OS) were analyzed for the intent-to
      treat population. RESULTS: At 7.6 years median follow-up, 384 recurrences or
      deaths had occurred with PEG-IFN-alpha-2b versus 406 in the observation group
      (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was
      39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1
      ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR,
      0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P =
      .006) were prolonged with PEG-IFN-alpha-2b. PEG-IFN-alpha-2b was discontinued for
      toxicity in 37% of patients. CONCLUSION: Adjuvant PEG-IFN-alpha-2b for stage III
      melanoma had a positive impact on RFS, which was marginally significant and
      slightly diminished versus the benefit seen at prior follow-up (median, 3.8
      years). No significant increase in DMFS or OS was noted in the overall
      population. Patients with ulcerated melanoma and lower disease burden had the
      greatest benefit.

PMID- 23008301
TI  - Randomized trial of short-course radiotherapy versus long-course chemoradiation
      comparing rates of local recurrence in patients with T3 rectal cancer: Trans
      Tasman Radiation Oncology Group trial 01.04.
AB  - PURPOSE: To compare the local recurrence (LR) rate between short-course (SC) and
      long-course (LC) neoadjuvant radiotherapy for rectal cancer. PATIENTS AND
      METHODS: Eligible patients had ultrasound- or magnetic resonance imaging-staged
      T3N0-2M0 rectal adenocarcinoma within 12 cm from anal verge. SC consisted of
      pelvic radiotherapy 5 * 5 Gy in 1 week, early surgery, and six courses of
      adjuvant chemotherapy. LC was 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, with
      continuous infusional fluorouracil 225 mg/m(2) per day, surgery in 4 to 6 weeks,
      and four courses of chemotherapy. RESULTS: Three hundred twenty-six patients were
      randomly assigned; 163 patients to SC and 163 to LC. Median potential follow-up
      time was 5.9 years (range, 3.0 to 7.8 years). Three-year LR rates (cumulative
      incidence) were 7.5% for SC and 4.4% for LC (difference, 3.1%; 95% CI, -2.1 to
      8.3; P = .24). For distal tumors (< 5 cm), six of 48 SC patients and one of 31 LC
      patients experienced local recurrence (P = .21). Five-year distant recurrence
      rates were 27% for SC and 30% for LC (log-rank P = 0.92; hazard ratio [HR] for
      LC:SC, 1.04; 95% CI, 0.69 to 1.56). Overall survival rates at 5 years were 74%
      for SC and 70% for LC (log-rank P = 0.62; HR, 1.12; 95% CI, 0.76 to 1.67). Late
      toxicity rates were not substantially different (Radiation Therapy Oncology
      Group/European Organisation for Research and Treatment of Cancer G3-4: SC, 5.8%;
      LC, 8.2%; P = .53). CONCLUSION: Three-year LR rates between SC and LC were not
      statistically significantly different; the CI for the difference is consistent
      with either no clinically important difference or differences in favor of LC. LC
      may be more effective in reducing LR for distal tumors. No differences in rates
      of distant recurrence, relapse-free survival, overall survival, or late toxicity
      were detected.

PMID- 23008302
TI  - Boulevard of broken dreams: drug approval for older adults with acute myeloid
      leukemia.

PMID- 23008303
TI  - Parenthood in survivors of Hodgkin lymphoma: an EORTC-GELA general population
      case-control study.
AB  - PURPOSE: We investigated the impact of Hodgkin lymphoma (HL) on parenthood,
      including factors influencing parenthood probability, by comparing long-term HL
      survivors with matched general population controls. PATIENTS AND METHODS: A Life
      Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in
      successive clinical trials. Responders were matched with controls (1:3 or 4) for
      sex, country, education, and year of birth (10-year groups). Controls were given
      an artificial date of start of treatment equal to that of their matched case. The
      main end point was presence of biologic children after treatment, which was
      evaluated by using conditional logistic regression analysis. Logistic regression
      analysis was used to analyze factors influencing spontaneous post-treatment
      parenthood. RESULTS: In all, 1,654 French and Dutch survivors were matched with
      6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After
      treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to
      0.87; P < .001) for survivors compared with controls. Of 898 survivors who were
      childless before treatment, 46.7% achieved post-treatment parenthood compared
      with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors
      with children before treatment, 12.4% became parents after HL treatment compared
      with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P < .001).
      Treatment with alkylating agents, second-line therapy, and age older than 35
      years at treatment appeared to reduce the chances of spontaneous post-treatment
      parenthood. CONCLUSION: Survivors of HL had slightly but significantly fewer
      children after treatment than matched general population controls. The difference
      concerned only survivors who had children before treatment and appears to have
      more personal than biologic reasons. The chance of successful post-treatment
      parenthood was 76%.

PMID- 23008304
TI  - How they do this.

PMID- 23008306
TI  - Treatment for early-stage hodgkin lymphoma: has radiotherapy had its day?

PMID- 23008305
TI  - Noninitiation of adjuvant chemotherapy in women with localized breast cancer: the
      breast cancer quality of care study.
AB  - PURPOSE: For some women, adjuvant chemotherapy for nonmetastatic breast cancer
      decreases recurrences and increases survival; however, patient-physician
      decisions regarding chemotherapy receipt can be influenced by medical and
      nonmedical factors. PATIENTS AND METHODS: We used a prospective cohort design and
      multivariate modeling to investigate factors related to noninitiation of
      chemotherapy among women with newly diagnosed breast cancer recruited from three
      US sites. We interviewed patients at baseline and during treatment on
      sociodemographic, tumor, and treatment decision-making factors. Patients were
      categorized according to National Comprehensive Cancer Network guidelines as
      those for whom chemotherapy was definitely indicated, clinically discretionary,
      or discretionary based on age greater than 70 years. RESULTS: Of 1,145 patients
      recruited, chemotherapy was clinically indicated for 392 patients, clinically
      discretionary for 459 patients, discretionary because of age for 169 patients,
      and not indicated for 93 patients; data were insufficient for 32 patients.
      Chemotherapy rates were 90% for those in whom chemotherapy was clinically
      indicated, 36% for those in whom it was discretionary because of clinical
      factors, and 19% for those in whom it was discretionary based on age greater than
      70 years. Nonreceipt of chemotherapy was associated with older age, more negative
      beliefs about treatment efficacy, less positive beliefs about chemotherapy, and
      more concern about adverse effects. In the two discretionary groups, clinical
      predictors of worse outcome (greater tumor size, positive nodes, worse grade, and
      estrogen receptor- and progesterone receptor-negative status) were associated
      with increased chemotherapy initiation. CONCLUSION: Utilization of adjuvant
      chemotherapy was most common among patients who, based on clinical criteria,
      would most likely benefit from it, patients with more positive than negative
      beliefs regarding treatment efficacy, and patients with few concerns about
      adverse effects.

PMID- 23008307
TI  - Waiting is the hardest part.

PMID- 23008309
TI  - Bone health in adult cancer survivorship.
AB  - Optimizing health outcomes, including prevention of osteoporotic fractures, is
      essential for promoting the well-being of the growing number of cancer survivors.
      Medical providers who participate in the care of cancer survivors should be aware
      that various cancer treatments may cause bone loss, which can increase the risk
      of subsequent of osteoporosis. Healthy bone remodeling is a balanced and dynamic
      equation between new bone formation and bone resorption. Aging, natural
      menopause, and cancer treatments such as surgical oophorectomy, gonadotropin
      releasing hormone agonists, chemotherapy-induced ovarian failure, androgen
      deprivation therapy, and aromatase inhibitors can all promote bone loss. The WHO
      Fracture Assessment Tool can be used as a clinical aid to assess an individual's
      osteoporotic fracture risk, with or without bone mineral density measurements
      obtained from dual-energy x-ray absorptiometry. Preventative strategies include
      adequate calcium and vitamin D supplementation and modifying risk factors such as
      alcohol intake, tobacco use, and lack of exercise. Bisphosphonate therapy and
      rank-ligand monoclonal antibody therapy are the most commonly used agents for
      management of bone loss resulting from cancer treatment. This review will
      summarize the mechanisms by which cancer treatments cause bone loss as well
      provide screening and treatment recommendations for the management of bone loss.

PMID- 23008308
TI  - Cancer- and cancer treatment-associated cognitive change: an update on the state
      of the science.
AB  - Cognitive changes associated with cancer and cancer treatments have become an
      increasing concern. Using breast cancer as the prototype, we reviewed the
      research from neuropsychological, imaging, genetic, and animal studies that have
      examined pre- and post-treatment cognitive change. An impressive body of research
      supports the contention that a subgroup of patients is vulnerable to post
      treatment cognitive problems. We also propose that models of aging may be a
      useful conceptual framework for guiding research in this area and suggest that a
      useful perspective may be viewing cognitive change in patients with cancer within
      the context of factors that influence the trajectory of normal aging.

PMID- 23008310
TI  - Metastatic human papillomavirus-positive nasopharyngeal carcinoma with an unusual
      pattern of aggressive hematogenous spread.

PMID- 23008311
TI  - Bronchoesophageal fistula and fatal hemoptysis after bevacizumab-containing
      chemotherapy without radiation in lung cancer.

PMID- 23008312
TI  - Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged
      acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia
      Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group.
AB  - PURPOSE: To evaluate the prognostic value of ecotropic viral integration 1 gene
      (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene
      rearrangements. PATIENTS AND METHODS: We identified 286 patients with AML with
      t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and
      Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment
      trials. Material was available from 177 AML patients for EVI1 expression
      analysis. RESULTS: We divided 286 MLL-rearranged AMLs into three subgroups:
      t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1
      overexpression (EVI1(+)) was found in 45.8% of all patients with t(11q23), with
      t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and
      t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three
      subgroups. Within all t(11q23) AMLs, EVI1(+) was the sole prognostic factor,
      predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003),
      relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P
      = .009). EVI1(+) AMLs with t(11q23) in first complete remission (CR) had a
      significantly better outcome after allogeneic transplantation compared with other
      consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1(-)
      t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and
      frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs,
      EVI1(+) again was the sole independent adverse prognostic factor for survival.
      CONCLUSION: Deregulated EVI1 expression defines poor prognostic subsets among AML
      with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1(+) MLL-rearranged
      AML seem to benefit from allogeneic transplantation in first CR.

PMID- 23008313
TI  - Tumor grade is associated with venous thromboembolism in patients with cancer:
      results from the Vienna Cancer and Thrombosis Study.
AB  - PURPOSE: Patients with cancer are at risk of venous thromboembolism (VTE). Tumor
      related factors could help estimate patients' individual risk for VTE. Currently,
      only scarce information on the association between tumor grade and VTE is
      available. We thus evaluated the role of tumor grade and its association with
      VTE. PATIENTS AND METHODS: The Vienna Cancer and Thrombosis Study is a
      prospective, observational cohort study including patients with newly diagnosed
      cancer or progression of disease after remission. Study end point is the
      occurrence of symptomatic VTE. RESULTS: Seven hundred forty-seven patients with
      solid tumors received follow-up for a median of 526 days. VTE occurred in 52
      patients (7.0%). At study inclusion, 468 patients had low-grade tumors (G1 and
      G2) and 279 had high-grade tumors (G3 and G4). In multivariable Cox regression
      analysis including tumor grade, tumor histology, tumor sites, stage, sex, and
      age, patients with high-grade tumors had a significantly higher risk of VTE
      compared with those with low-grade tumors (hazard ratio, 2.0; 95% CI, 1.1 to 3.5;
      P = .015). The cumulative probability of developing VTE after 6 months was higher
      in patients with high-grade tumors than in those with low-grade tumors (8.2% v
      4.0%; log-rank test P = .037). Patients with high-grade tumors had higher D-dimer
      levels (P = .008) and leukocyte counts (P < .001), and lower hemoglobin levels (P
      = .008). CONCLUSION: The tumor grade may help identify patients with cancer who
      are at high risk of VTE. The association of tumor grade with recently identified
      biomarkers indicates a link between tumor differentiation and pathogenesis of
      cancer-associated VTE.

PMID- 23008314
TI  - Cancer Rehabilitation Evaluation System (CARES) and CARES-SF now publicly
      available.

PMID- 23008315
TI  - Paraneoplastic acanthosis nigricans with cutaneous and mucosal papillomatosis
      preceding recurrence of a gastric adenocarcinoma.

PMID- 23008316
TI  - Lifestyle factors in cancer survivorship.
AB  - Lifestyle factors have been linked to the risk of developing many common
      malignancies and, increasingly, to prognosis. Observational evidence has shown a
      relationship between so-called energy balance factors (ie, diet, physical
      activity, and body weight) and risk of cancer recurrence and mortality in cancers
      of the breast, prostate, colon and, perhaps, other cancers. Interventional work
      has shown that individuals who make favorable changes in these lifestyle factors
      after cancer diagnosis feel better, experience less fatigue, and may possibly
      even decrease risk of cancer recurrence. Other lifestyle behaviors, such as
      smoking and alcohol consumption, have also been linked to the development of
      common cancers and may have important health consequences for cancer survivors.
      This article reviews the evidence that links lifestyle factors to cancer
      outcomes, provides clinical recommendations for cancer survivors, and describes
      future directions for lifestyle research in cancer survivors.

PMID- 23008317
TI  - Role of financial relationships in economic analyses of targeted therapies in
      oncology remains unclear.

PMID- 23008318
TI  - Long-term and late effects of germ cell testicular cancer treatment and
      implications for follow-up.
AB  - Germ cell testicular cancer (TC) represents a malignancy with high cure rates.
      Since the introduction of cisplatin-based chemotherapy in the late 1970s, the 5
      year survival rate has increased considerably, and it is currently above 95%.
      Because TC is usually diagnosed before the age of 40 years, these men can expect
      to live for another 40 to 50 years after being successfully treated. This
      success, however, is hampered by an increased risk of long-term and late effects
      of treatment. Secondary malignant neoplasms and cardiovascular disease represent
      the most common potentially life-threatening late effects, typically occurring
      more than 10 years after treatment. Other long-term effects include pulmonary
      toxicity, nephrotoxicity, neurotoxicity, decreased fertility, hypogonadism, and
      psychosocial problems. The incidence and time to onset of these various adverse
      effects vary according to treatment type and intensity. There is still little
      knowledge about underlying mechanisms and genetic susceptibility of the various
      adverse effects. Apart from treatment burden, it is not yet possible to identify
      patients who are at high risk for certain late effects after TC treatment. In
      this clinical review, we present the current status regarding different somatic
      and psychosocial long-term late effects after treatment for TC, based on Medline
      searches and our own research. Moreover, we postulate recommendations for general
      medical evaluations that should begin after treatment is completed and continue
      during follow-up.

PMID- 23008319
TI  - Fertility (male and female) and menopause.
AB  - The impact of oncologic treatments on fertility and menopausal symptoms is often
      significant for patients with cancer. Surgery, radiation, and chemotherapy can
      all damage the reproductive organs or the hypothalamic pituitary axis that
      controls them, impairing fertility and causing hormonally mediated symptoms such
      as hot flashes. Understanding these risks and strategies to mitigate them may
      substantially improve cancer survivorship care. For both female and male patients
      who desire a future biologic child, there are a variety of fertility preservation
      techniques that should be considered. For cancer survivors who experience
      menopausal symptoms, lifestyle changes may be beneficial, and hormonal and
      nonhormonal pharmacologic agents are well proven to reduce symptom burden.

PMID- 23008320
TI  - Troublesome symptoms in cancer survivors: fatigue, insomnia, neuropathy, and
      pain.
AB  - Patients with cancer suffer from a variety of symptoms associated with both
      cancer and its treatment. These symptoms may lead to a decreased quality of life
      for patients and can affect compliance with cancer therapies. The importance of
      adequately treating cancer-related symptoms is gaining more attention but,
      overall, many symptoms remain underdiagnosed and undertreated. Fatigue, insomnia,
      neuropathy, and pain are among the most common troublesome symptoms experienced
      by cancer survivors. This article will focus on the management of these symptoms,
      including an assessment of the current research and proposed best- management
      practices.

PMID- 23008321
TI  - Chronic lymphocytic leukemia after chronic myeloid leukemia in the same patient:
      two different genomic events and a common treatment?

PMID- 23008322
TI  - Sexuality in adult cancer survivors: challenges and intervention.
AB  - Sexual dysfunction is one of the most common and distressing consequences of
      cancer treatment. Although some treatment-related sexual adverse effects are
      short-term, many survivors face long-term effects such as treatment-induced
      menopause, altered gonadal function, and significant surgical disfigurement.
      Profound sexual dysfunction has been shown to have a significant negative effect
      on quality of life. Although these problems have been well documented and there
      are a range of intervention strategies that can help patients cope with treatment
      related sexual problems, many survivors do not feel prepared for potential sexual
      changes and often do not receive adequate support to manage sexual dysfunction.
      Numerous barriers contribute to this underprovided aspect of survivorship care,
      including lack of provider training and access to readily available resources. In
      addition, psychological, relational, and cultural factors significantly influence
      sexuality but are often not taken into consideration in research and clinical
      practice. By taking an integrative approach and providing survivors with
      appropriate screening, information, and support, sexual dysfunction and
      accompanying distress can be significantly alleviated. In this article, we aim to
      provide a concise review of the most common sexual problems experienced by
      survivors and highlight some of the most promising evidence-based practices for
      assessment and intervention. We also address limitations encountered in research
      and practice and explore future directions, including suggestions for adopting an
      integrative treatment model to address sexual dysfunction in a cancer
      survivorship treatment setting.

PMID- 23008323
TI  - Erdheim-Chester disease harboring the BRAF V600E mutation.

PMID- 23008324
TI  - Is tanning bed exposure associated with aggressive basal cell carcinoma?

PMID- 23008325
TI  - Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation
      plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with
      resected pancreatic adenocarcinoma.
AB  - PURPOSE: Adjuvant chemotherapy prolongs survival in patients with pancreatic
      cancer, but its benefit is limited. Long-term survival times of up to 44 months
      after adjuvant chemoradioimmunotherapy in phase II trials motivated the present
      study. PATIENTS AND METHODS: Between 2004 and 2007, 132 R0/R1 resected patients
      received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN alpha
      2b) plus radiotherapy followed by two cycles of FU (arm A, n=64) or six cycles of
      FU monotherapy (arm B, n=68). One hundred ten patients (arm A, n=53; arm B, n=57)
      received at least one dose of the study medication, and these patients composed
      the per-protocol (PP) population. Biomarkers were analyzed longitudinally for
      their predictive value. RESULTS: Median survival for all randomly assigned
      patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months
      (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B:
      95% CI, 0.66 to 1.53; P=.99). Median survival for the PP population was 32.1
      months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to
      38.6 months) in arm B (P=.49). Eighty-five percent of patients in arm A and 16%
      of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was
      temporarily negatively affected in arm A. CONCLUSION: The FU, cisplatin, and IFN
      alpha-2b plus radiotherapy regimen did not improve the survival compared with FU
      monotherapy. Given the substantial adverse effects, this treatment can currently
      not be recommended. Nevertheless, the outcome in both arms represents the best
      survival, to our knowledge, ever reported for patients with resected pancreatic
      cancer in randomized controlled trials. Future studies will demonstrate whether
      immune response to IFN alpha-2b challenge has a predictive value.

PMID- 23008326
TI  - Sexuality and intimacy after definitive treatment and subsequent androgen
      deprivation therapy for prostate cancer.
AB  - There are more than 2 million prostate cancer survivors in the United States.
      Primary therapy with surgery or radiation results in permanent changes in sexual
      function. More than half of these men are subsequently treated with androgen
      deprivation therapy (ADT) at some point. The addition of ADT further compromises
      sexuality, intimacy, and a couple's relationship. This review will highlight the
      challenges faced by patients and couples and reveal the tremendous need for
      better education of physicians, patients, and couples as well as for more
      research in sexuality and intimacy with the goal of improving quality of life for
      this large population of survivors. Suggestions for clinicians to better help
      patients and their partners regarding sexuality and intimacy are offered.

PMID- 23008327
TI  - Journal of Clinical Oncology update on progress in cancer survivorship care and
      research.

PMID- 23008328
TI  - Treatment of the future, today?

PMID- 23008329
TI  - Invasive mucormycosis in an immunocompetent patient with allergic fungal
      rhinosinusitis.

PMID- 23008330
TI  - Auditory-perceptual speech outcomes and quality of life after total laryngectomy.
AB  - OBJECTIVE: (1) To determine potential relationships between speech
      intelligibility, acceptability, and self-reported quality of life (QOL) after
      total laryngectomy and (2) to determine whether relationships are stronger when
      QOL is measured by a head and neck cancer-specific or discipline-specific QOL
      scale. STUDY DESIGN: Cross-sectional. SETTING: University-based laboratory and
      speech clinic. SUBJECTS AND METHODS: Twenty-five laryngectomized individuals
      completed disease-specific (University of Washington Quality of Life; UW-QOL) and
      discipline-specific (Voice Handicap Index-10; VHI-10) QOL scales. They also
      provided audio recordings that included the Sentence Intelligibility Test (SIT)
      and a reading passage. Thirty-three listeners transcribed the SIT sentences to
      yield intelligibility scores. Fifteen additional listeners judged speech
      acceptability of the reading passage using rating scales. RESULTS: The QOL scores
      were moderate across the UW-QOL physical (mean = 77.63) and social-emotional
      (mean = 78.02) subscales and the VHI-10 (mean = 17.91). Speech acceptability and
      intelligibility varied across the samples, with acceptability only moderately
      related to intelligibility (r = 0.41, P < .05). Relationships were weak between
      ratings of intelligibility and self-reported QOL (range, r = 0.00-0.22) and weak
      to moderate between acceptability with QOL (range, r = 0.01-0.46). The only
      statistically significant, but moderate, relationship was found between speech
      acceptability with the UW-QOL speech subscore (r = 0.46, P < .05). CONCLUSION:
      Listeners' ratings of speech acceptability and intelligibility were not strongly
      predictive of disease-specific or voice-related QOL, suggesting that listener
      rated and patient-reported outcomes are complementary.

PMID- 23008331
TI  - Single-incision transaxillary robotic thyroidectomy: challenges and limitations
      in a North American population.
AB  - OBJECTIVE: We reviewed our initial experience with robotic thy-roidectomy to
      identify challenges and limitations of this new surgical approach when applied to
      a North American population. STUDY DESIGN: Case series. SETTING: Academic
      institution. SUBJECTS/METHODS: Retrospective review of 18 consecutive robotic
      thyroid lobectomies performed from February 2010 to April 2012 involving 16
      female patients. Two patients underwent robot-assisted completion thyroidectomy a
      few months following the initial thyroid surgery, one for cancer and the other
      for goiter. RESULTS: Median age was 47.5 years (range, 18-62 years), and median
      body mass index was 28.7 (range, 19.4-44.5). Median thyroid nodule size was 2.9
      cm (range, 1.1-4.7 cm). All but 1 case (6%) was performed successfully via single
      axillary incision. There was no conversion to an open approach. Median operative
      time was 170 minutes (range, 95-220 minutes), and median blood loss was 12.5 mL
      (range, 5-75 mL). Complications occurred in 4 cases (22%) to include temporary
      vocal cord pareses (n = 3) and a postoperative hematoma that required
      exploration. Median hospital stay was 2 days (range, 1-3 days). CONCLUSION:
      Single-incision transaxillary robotic thyroidectomy can be technically
      challenging in North American patients with a larger body frame due to difficulty
      in optimal placement of all 4 robotic instruments via a single axillary incision.
      All 3 cases of temporary vocal cord paresis occurred early in our experience and
      may have been due to our relative inexperience with this new approach and
      associated instrumentation. Other limitations include less than optimal
      visualization of the recurrent laryngeal nerve in the contralateral lobe as well
      as poor access to the substernal region. LEVEL OF EVIDENCE: 4.

PMID- 23008332
TI  - Home parenteral nutrition tutorial.
AB  - The nutrition support practitioner may be called upon to help coordinate care at
      home for a patient who requires prolonged intravenous nutrition after he or she
      becomes stable enough to leave the hospital. This tutorial reviews the many
      concepts that must be considered to manage this type of care successfully.

PMID- 23008333
TI  - A role for the RNA pol II-associated PAF complex in AID-induced immune
      diversification.
AB  - Antibody diversification requires the DNA deaminase AID to induce DNA instability
      at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine
      deamination, AID requires single-stranded DNA and needs to gain access to Ig
      loci, with RNA pol II transcription possibly providing both aspects. To
      understand these mechanisms, we isolated and characterized endogenous AID
      containing protein complexes from the chromatin of diversifying B cells. The
      majority of proteins associated with AID belonged to RNA polymerase II elongation
      and chromatin modification complexes. Besides the two core polymerase subunits,
      members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID.
      We show that AID associates with RNA polymerase-associated factor 1 (PAF1)
      through its N-terminal domain, that depletion of PAF complex members inhibits AID
      induced immune diversification, and that the PAF complex can serve as a binding
      platform for AID on chromatin. A model is emerging of how RNA polymerase II
      elongation and pausing induce and resolve AID lesions.

PMID- 23008336
TI  - Retraction of "The Motivated Self: Self-Affirmation and the Better-Than-Average
      Effect"
AB  - Guenther, C.L, & Timberlake, E.A. (2012). The Motivated Self: Self-Affirmation
      and the Better-Than-Average Effect. Personality and Social Psychology Bulletin
      (Original DOI: 10.1177/0146167212457074).

PMID- 23008334
TI  - Induction of tumoricidal function in CD4+ T cells is associated with concomitant
      memory and terminally differentiated phenotype.
AB  - Harnessing the adaptive immune response to treat malignancy is now a clinical
      reality. Several strategies are used to treat melanoma; however, very few result
      in a complete response. CD4(+) T cells are important and potent mediators of anti
      tumor immunity and adoptive transfer of specific CD4(+) T cells can promote tumor
      regression in mice and patients. OX40, a costimulatory molecule expressed
      primarily on activated CD4(+) T cells, promotes and enhances anti-tumor immunity
      with limited success on large tumors in mice. We show that OX40 engagement, in
      the context of chemotherapy-induced lymphopenia, induces a novel CD4(+) T cell
      population characterized by the expression of the master regulator eomesodermin
      that leads to both terminal differentiation and central memory phenotype, with
      concomitant secretion of Th1 and Th2 cytokines. This subpopulation of CD4(+) T
      cells eradicates very advanced melanomas in mice, and an analogous population of
      human tumor-specific CD4(+) T cells can kill melanoma in an in vitro system. The
      potency of the therapy extends to support a bystander killing effect of antigen
      loss variants. Our results show that these uniquely programmed effector CD4(+) T
      cells have a distinctive phenotype with increased tumoricidal capability and
      support the use of immune modulation in reprogramming the phenotype of CD4(+) T
      cells.

PMID- 23008335
TI  - Tryptophan hydroxylase-1 regulates immune tolerance and inflammation.
AB  - Nutrient deprivation based on the loss of essential amino acids by catabolic
      enzymes in the microenvironment is a critical means to control inflammatory
      responses and immune tolerance. Here we report the novel finding that Tph-1
      (tryptophan hydroxylase-1), a synthase which catalyses the conversion of
      tryptophan to serotonin and exhausts tryptophan, is a potent regulator of
      immunity. In models of skin allograft tolerance, tumor growth, and experimental
      autoimmune encephalomyelitis, Tph-1 deficiency breaks allograft tolerance,
      induces tumor remission, and intensifies neuroinflammation, respectively. All of
      these effects of Tph-1 deficiency are independent of its downstream product
      serotonin. Because mast cells (MCs) appear to be the major source of Tph-1 and
      restoration of Tph-1 in the MC compartment in vivo compensates for the defect,
      these experiments introduce a fundamentally new mechanism of MC-mediated immune
      suppression that broadly impacts multiple arms of immunity.

PMID- 23008337
TI  - Does volunteering for sex offender treatment matter? Using propensity score
      analysis to understand the effects of volunteerism and treatment on recidivism.
AB  - A common critique of program evaluations of prison-based sex offender treatment
      holds that the samples inherently show selection bias because the participants
      typically volunteer for treatment. To address this critique, we used propensity
      score analysis to assess the influence of volunteerism on treatment effects. We
      examined recidivism outcomes for a sample of participants who volunteered for
      treatment, of whom some participated in treatment (n = 161) and some did not (n =
      282) and compared these outcomes to the recidivism rate of a matched sample of
      nonvolunteers for treatment (n = 443). The primary finding is that offenders who
      volunteered for treatment did not demonstrate any differences in recidivism rates
      when matched with and compared to inmates who did not volunteer to participate in
      treatment. Furthermore, our results revealed that there were a number of
      significant differences between unmatched volunteers and unmatched nonvolunteers,
      perhaps most importantly in their risk for future recidivism as measured by the
      STATIC-99 risk assessment. We discuss study strengths and limitations and present
      the implications of the findings for policy, practice, and research. 

PMID- 23008338
TI  - Risks of small-for-gestational-age births in immigrants: a nationwide
      epidemiological study in Sweden.
AB  - AIM: To examine if there is an association between country of birth in parents
      and small-for-gestational-age (defined as a birthweight of more than two standard
      deviations (SDs) below the mean) in first singletons births. METHODS: In this
      follow-up study, national population and healthcare registers were used to
      identify small-for-gestational-age births in all first singleton births in Sweden
      between 1 January 1982 and 31 December 2006. Odds ratios, standardised with
      regard to maternal age at birth, period of birth, marital status, family income,
      geographical region, employment, maternal height, and smoking history, were
      estimated by maternal and paternal country of birth. Singletons with both parents
      born in Sweden were used as reference group. RESULTS: There were 1,060,467
      records for first singletons births over the study period, of whom 3.5% were
      small-for-gestational-age. The rate was higher in newborns with non-Swedish born
      than in those with Swedish born mothers (4.1 and 3.3%, respectively). Immigrants
      from Southern European countries, Africa, and Asia had higher risks of small-for
      gestational-age in than those in the reference group, and the risks were even
      higher in compatriot parents. CONCLUSIONS: Country of birth affected the risk of
      small-for-gestational-age. Maternity care should pay a special attention to
      pregnancies in certain population groups.

PMID- 23008340
TI  - Wound care in China: from repair to regeneration.
AB  - Wounds in China are severe problems, and China has a huge demand for tissue
      repair and regeneration. In the past decades, there has been significant
      development in genetics, auxology, stem cell biology, and tissue engineering,
      which have been further translated into and integrated with clinical treatment of
      tissue injury. In China, this synergy has contoured the discipline of tissue
      repair and regeneration to be one of the best and fastest performing disciplines
      with regard to bench-to-bed connection and translation.

PMID- 23008339
TI  - Efficacy and tolerability of nebivolol: does age matter? A retrospective analysis
      of three randomized, placebo-controlled trials in stage I-II hypertension.
AB  - OBJECTIVES: This retrospective analysis examined the efficacy and tolerability of
      nebivolol, a beta(1)-selective, vasodilatory beta-blocker, in four different age
      groups of patients with hypertension. METHODS: Data were pooled from three 12
      week, randomized, placebo-controlled trials (placebo, n = 205; nebivolol [1.25
      30/40 mg/day], n = 1811) and stratified into age quartiles (Group 1: 22-46 years;
      Group 2: 47-53 years; Group 3: 54-62 years; Group 4: 63-84 years). Only patients
      treated with placebo and the three commonly used nebivolol dosages (5, 10, and 20
      mg/day) are presented. Baseline-to-endpoint changes in trough sitting diastolic
      blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) were
      analyzed for each age quartile using an analysis of covariance (ANCOVA) model.
      Tolerability was assessed by means of adverse event (AE) rates. RESULTS: The
      analysis comprised 205 placebo-treated patients and 1380 patients treated with
      nebivolol dosages of 5, 10, or 20 mg/day. Older age was associated with higher
      SBP values at baseline. In all age groups, each of the three most frequently used
      nebivolol dosages significantly reduced DBP, compared with placebo (-9.1 to -11.8
      mmHg versus -3.4 to -5.9 mmHg; p <= 0.008 overall). For SBP, a statistically
      significant effect versus placebo was observed for all dosages and age groups
      except for 5 and 10 mg/day in Group 4. Within each group, treatment with
      nebivolol (all three dosages) and placebo resulted in similar AE rates
      (nebivolol: 26.1-36.6%; placebo: 36.2-42.6%) and AE-related discontinuation rates
      (1.8-3.8% versus 0-4.3%). In each age group, there were no significant nebivolol
      placebo differences in the rates of patients who experienced clinically
      significant changes or abnormal endpoint levels of metabolic parameters.
      CONCLUSIONS: This retrospective analysis suggests that nebivolol monotherapy is
      efficacious and well tolerated across various age groups, with the efficacy in
      reducing SBP somewhat diminishing in patients over 62 years of age.

PMID- 23008341
TI  - Looking east.

PMID- 23008342
TI  - The investigation of demographic characteristics and the health-related quality
      of life in patients with diabetic foot ulcers at first presentation.
AB  - To investigate the characteristics of diabetic patients with foot ulcers, their
      health-related quality of life (HRQoL), and the link between them. The study
      population included 131 consecutive patients presenting in a diabetic foot clinic
      with a new foot ulcer between December 1, 2011, and May 1, 2012. The authors
      collected sociodemographic data, foot and ulcer characteristics using the Wagner
      Grade, and HRQoL (using the SF-36 Scale) information; 54.2% of the patients were
      in Wagner 2 or Wagner 3 categories. In all the 8 SF-36 subscales and in the SF-36
      summary scales, the patients with diabetic foot ulcer had significantly poorer
      HRQoL than the general population in China (P < .01). Their Wagner Grade had
      negative correlation with all the SF-36 subscales and the summary scales (P <
      .05). In conclusion, new diabetic foot ulcers were already in poor condition when
      patients first visited the diabetic foot clinic. Concomitantly, patients had
      worse HRQoL compared with the general population. More effective interventions
      are needed to improve their self-care level and HRQoL.

PMID- 23008343
TI  - Extremity trauma, dressings, and wound infection: should every acute limb wound
      have a silver lining?
AB  - The manner in which high-energy transfer limb injuries are dressed can alter the
      wound environment through manipulation of the bacterial burden, thus minimizing
      tissue degradation and influencing healing potential. Infection is the principal
      complication of such wounds, and antiseptic soaked gauze is accepted in early
      coverage of extremity wounds despite a lack of evidence to support this practice.
      There has been resurgence in the use of silver in acute wounds, through dressings
      manipulated to deliver sustained elemental silver to the wound interface. In
      vitro and in vivo experimentation of silver dressings are characterized however
      by methodological compromise, primarily through lack of similarity of models to
      the physiology of the healing wound. Results from in vitro studies caution
      against the use of silver because of evidence of cytotoxicity, but this is not
      reproduced in in vivo or clinical experimentation, leading to ambiguity. Review
      of silver dressing application in burns and chronic wound studies fails to
      support its use over other dressing systems. Similarly, evidence for the use of
      silver in acute limb wounds is lacking. This article provides a comprehensive
      overview of the use of silver dressings in acute wound care and highlights in
      particular the paucity of evidence regarding its routine use in extremity injury.

PMID- 23008344
TI  - Reduced dermis thickness and AGE accumulation in diabetic abdominal skin.
AB  - Dermatological problems in diabetes might play an important role in the
      spontaneous ulcers and impaired wound healing that are seen in diabetic patients.
      Investigation of the cause of diabetic skin disorders is critical for identifying
      effective treatment. The abdominal full-thickness skin tissues of 33 patients (14
      nondiabetic and 19 diabetic) were analyzed. The cell viability and
      malondialdehyde (MDA) production of fibroblasts were measured after advanced
      glycosylation end product (AGE)-bovine serum albumin (BSA) exposure. Cutaneous
      histological observation showed reduced thickness of the diabetic abdominal
      dermis with morphological characteristics of obscured multilayer epithelium and
      shortened, thinned, and disorganized collagen fibrils with focal chronic
      inflammatory cell infiltration when compared with controls of the same age.
      Accumulation of AGEs in diabetic skin was prominent. Less hydroxyproline, higher
      myeloperoxidase activity, and increased MDA content were detected in diabetic
      skin. In vitro, the time- and dose-dependent inhibitory effects of AGE-BSA on
      fibroblast viability as well as the fact that AGE-BSA could promote MDA
      production of fibroblasts were shown. It is shown that the accumulation of AGEs
      in diabetic skin tissue induces an oxidative damage of fibroblasts and acts as an
      important contributor to the thinner diabetic abdominal dermis. The authors
      believe that diabetic cutaneous properties at baseline may increase the
      susceptibility to injury, and diabetic wounds possess atypical origin in the
      repair process.

PMID- 23008345
TI  - The experimental study of hemodynamic changes and pathological morphology after
      artery anastomosis.
AB  - The purpose of this article is to dynamically observe hemodynamic and medium-term
      pathomorphological changes and to investigate the pathophysiological variation at
      the vascular anastomotic stoma. Eighteen New Zealand white rabbits underwent
      right common carotid artery in situ anastomosis, and the hemodynamic changes of
      anastomotic stoma were recorded by color Doppler ultrasonography before surgery
      and 5 minutes, 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, 12 weeks, and 16 weeks
      after surgery. Pathological sections of stoma were made and the
      pathomorphological changes viewed. Artery anastomoses were preformed successfully
      in 15 rabbits; 4 rabbits suffered postoperative death. It took 1.22 +/- 0.77
      hours to complete every operation. All the data involved, mean velocity, peak
      systolic velocity, and resistant index, had no significant differences between
      preoperative and postoperative follow-up. The obvious differences were found in
      the diameters of stoma 5 minutes, 1 week, 2 weeks, and 3 weeks after operation (P
      values were .002, .001, .003, and .008, respectively). The variance of stoma
      diameters 2 weeks later was also different from those after 1 week, but no other
      differences were observed during other weeks. The decrease in stoma diameters
      after anastomosis was clear, with the maximum decrease occurring 2 weeks after
      the operation, after which the diameters of stoma became stable 16 weeks after
      the operation. Some collagens around anastomoses could be found by the
      pathological sections of stoma, which indicated that the deposition of collagen
      might be related to the decrease in stoma diameter.

PMID- 23008347
TI  - Involvement of the mitochondria-caspase pathway in HeLa cell death induced by 2
      ethanolamino-2-demethoxy-17-ethanolimino-hypocrellin B (EAHB)-mediated
      photodynamic therapy.
AB  - In order to elucidate the mechanism of cytotoxicity photoinduced by 2
      ethanolamino-2-demethoxy-17-ethanolimino-hypocrellin B (EAHB), a derivative of
      hypocrellin B (HB), cellular uptake, subcellular localization as well as
      photodynamic therapy (PDT) efficiency of EAHB, and cell apoptosis photoinduced by
      EAHB were investigated in HeLa cells by laser confocal fluorescence microscopy, 3
      (4,5-Dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, flow
      cytometry, DNA fragmentation on agarose gel, and Western blot. The results showed
      EAHB was distributed throughout the cytoplasm of the cell, with no detectable
      penetration into the nucleus. The proportion of dead cells increased with
      increases in both the dosage of light and the concentration of EAHB. Its
      phototoxicity to HeLa cells proceeded via apoptosis. The EAHB-PDT treatment
      induced a cytochrome c release from the mitochondria into the cytosol followed by
      the activation of both caspase 3 and caspase 9 in HeLa cells. The results
      suggested that EAHB-PDT treatment induced apoptosis in HeLa cells, and the
      cellular apoptosis involved a mitochondria-/caspase-dependent mechanism.

PMID- 23008348
TI  - Zinc signals in neutrophil granulocytes are required for the formation of
      neutrophil extracellular traps.
AB  - Zinc signals, i.e. changes in the free intracellular Zn(2+)concentration, are an
      integral component of signal transduction in several immune cells. The aim of the
      present study was to investigate if this is also the case in neutrophil
      granulocytes. One neutrophil function is NETosis, the release of a matrix
      composed of DNA, chromatin and granule proteins to capture extracellular bacteria
      within so-called neutrophil extracellular traps (NET). NETosis can be induced by
      the protein kinase C (PKC) activator 12-myristate 13-acetate (PMA). PMA treatment
      led to a zinc signal in neutrophil granulocytes. NETosis was inhibited when the
      zinc signal was sequestered by the membrane permeable high affinity chelator
      N,N,N',N',-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN). PKC-mediated NET
      formation depends on the production of reactive oxygen species (ROS) by NADPH
      oxidase. Inhibition of NADPH oxidase with diphenyleneiodonium chloride blocked
      ROS formation and NETosis, as well as the zinc signal. TPEN, however, had no
      effect on PKC activity and ROS production, indicating that Zn(2+) is not required
      for activation of PKC, but for signals downstream of ROS production. In
      conclusion, zinc signals are an essential component of the ROS-dependent signal
      transduction leading to NETosis.

PMID- 23008350
TI  - The role of communities in advancing the goals of the Movement for Global Mental
      Health.
AB  - This special section of Transcultural Psychiatry explores the local-global spaces
      of engagement being opened up by the Movement for Global Mental Health, with
      particular emphasis on the need for expanded engagement with local communities.
      Currently the Movement places its main emphasis on scaling up mental health
      services and advocating for the rights of the mentally ill, framed within
      universalised western understandings of health, healing and personhood. The
      papers in this section emphasise the need for greater attention to the impacts of
      context, culture and local survival strategies on peoples' responses to adversity
      and illness, greater acknowledgement of the agency and resilience of vulnerable
      communities and increased attention to the way in which power inequalities and
      social injustices frame peoples' opportunities for mental health. In this
      Introduction, we highlight ways in which greater community involvement opens up
      possibilities for tackling each of these challenges. Drawing on community health
      psychology, we outline our conceptualisation of "community mental health
      competence" defined as the ability of community members to work collectively to
      facilitate more effective prevention, care, treatment and advocacy. We highlight
      the roles of multi-level dialogue, critical thinking and partnerships in
      facilitating both the "voice" of vulnerable communities as well as "receptive
      social environments" where powerful groups are willing to recognise communities'
      needs and assist them in working for improved well-being. Respectful local-global
      alliances have a key role to play in this process. The integration of local
      community struggles for mental health into an energetic global activist Movement
      opens up exciting possibilities for translating the Movement's calls for improved
      global mental health from rhetoric to reality.

PMID- 23008349
TI  - Molecular basis for the increased polymyxin susceptibility of Klebsiella
      pneumoniae strains with under-acylated lipid A.
AB  - The impact of under-acylation of lipid A on the interaction between Klebsiella
      pneumoniae LPS and polymyxins B and E was examined with fluorometric and
      calorimetric methods, and by (1)H NMR, using a paired wild type (WT) and the
      DeltalpxM mutant strains B5055 and B5055DeltalpxM, which predominantly express
      LPS with hexa- and penta-acylated lipid A structures respectively. LPS from
      B5055DeltalpxM displayed a fourfold increased binding affinity for polymyxins B
      and E compared with the B5055 WT LPS. EC50 values were consistent with polymyxin
      minimum inhibitory concentration (MIC) values for each strain. Accordingly,
      polymyxin exposure considerably enhanced the permeability of the B5055DeltalpxM
      OM. Analysis of the melting profiles of isolated LPS aggregates suggested that
      bactericidal polymyxin activity may relate to the acyl chains' phase of the outer
      membrane (OM). The enhanced polymyxin susceptibility of B5055DeltalpxM may be
      attributable to the favorable insertion of polymyxins into the more fluid OM
      compared with B5055. Molecular models of the polymyxin B-lipid A complex
      illuminate the key role of the lipid A acyl chains for complexation of polymyxin.
      The data provide important insight into the molecular basis for the increased
      polymyxin susceptibility of K. pneumoniae strains with under-acylated lipid A.
      Under-acylation appears to facilitate the integration of the N-terminal fatty
      acyl chain of polymyxin into the OM resulting in an increased susceptibility to
      its antimicrobial activity/activities.

PMID- 23008351
TI  - Understanding the benefits and challenges of community engagement in the
      development of community mental health services for common mental disorders:
      lessons from a case study in a rural South African subdistrict site.
AB  - Against the backdrop of a large treatment gap for mental disorders in low- to
      middle-income countries (LMICs), the 2007 Lancet series on global mental health
      calls for a scaling up of mental health services. Community participation is
      largely harnessed as one strategy to facilitate this call. Using a participatory
      implementation framework for the development of mental health services for common
      mental disorders (CMDs) in a rural subdistrict in South Africa as a case study,
      this study sought to understand the benefits and challenges of community
      participation beyond that of scaling up. Qualitative process evaluation involving
      interviews with service providers and users was employed. The results suggest
      that in addition to promoting mobilization of resources and actions for scaling
      up mental health services, community participation can potentially contribute to
      more culturally competent services and personal empowerment of recipients of
      care. In addition, community participation holds promise for engendering
      community-led public health actions to ameliorate some of the social determinants
      of mental ill health. Challenges include that community members involved in these
      activities are mainly marginalized women, who have limited power to achieve
      structural change, including cultural practices that may be harmful to the mental
      health of women and children. We conclude that in addition to contributing to
      scaling up mental health services, community participation can potentially
      promote the development of culturally competent mental health services and
      greater community control of mental health.

PMID- 23008352
TI  - Pathologising healthy children? A review of the literature exploring the mental
      health of HIV-affected children in sub-Saharan Africa.
AB  - This article reviews the expanding body of literature that examines the mental
      health of HIV-affected children in sub-Saharan Africa. Focusing on primary
      research across disciplines and methodologies, the review examines the use of
      universalistic assumptions about childhood adversity and mental health in driving
      forward this body of research. Of the 31 articles identified for this review, 23
      had a focus on the psychological distress experienced by HIV-affected children,
      while only 8 explored social psychological pathways to improved mental health,
      resilience and coping. The article argues that this preoccupation with pathology
      reflects global assemblages of definitions, understandings and practices that
      constitute the global mental health framework. While such a focus is useful for
      policy interventions and the mobilisation of resources to support children living
      in HIV-affected communities, it overshadows more culturally relevant and
      strengths-based conceptualisations of how mental health is understood and can be
      achieved in different parts of Africa. Furthermore, a continued focus on the
      psychological distress experienced by HIV-affected children runs the risk of
      medicalising their social experiences, which in turn may transform the social
      landscape in which children give meaning to loss and difficult experiences. The
      article concludes that mental health professionals and researchers need to take
      heed of the biopolitical implications of their work, and argues for more
      community-oriented and resilience-enhancing research that brings forward the
      voices of local people to inform interventions tackling the psychosocial
      challenges inevitably experienced by many children in sub-Saharan Africa.

PMID- 23008353
TI  - Afterword: against "global mental health".

PMID- 23008354
TI  - An unruly coming of age: the benefits of discomfort for global mental health.

PMID- 23008355
TI  - Evidence-based psychological interventions for adult survivors of torture and
      trauma: a 30-year review.
AB  - In this paper we review research evidence on psychosocial interventions for adult
      survivors of torture and trauma. We identified 40 studies from 1980 to 2010 that
      investigated interventions for adult survivors of torture and trauma. Population
      subtypes include resettled refugees, asylum seekers, displaced persons, and
      persons resident in their country of origin. Settings include specialized
      services for torture and trauma, specialized tertiary referral clinics, community
      settings, university settings, as well as psychiatric and multidisciplinary
      mental health services. Interventions were delivered as individual or group
      treatments and lasted from a single session to 19 years duration. The studies
      employed randomized controlled trials, nonrandomized comparison studies and
      single cohort follow-up studies. In all, 36 of the 40 studies (90%) demonstrated
      significant improvements on at least one outcome indicator after an intervention.
      Most studies (60%) included participants who had high levels of posttraumatic
      stress symptomatology. Improvements in symptoms of posttraumatic stress,
      depression, anxiety, and somatic symptoms were found following a range of
      interventions. Little evidence was available with regard to the effect on
      treatment outcomes of the amount, type, or length of treatment, the influence of
      patient characteristics, maintenance of treatment effects, and treatment outcomes
      other than psychiatric symptomatology. The review highlights the need for more
      carefully designed research that addresses the shortcomings of current studies
      and that integrates the experience of expert practitioners.

PMID- 23008359
TI  - Obituary for prof. Dr. Wolfgang M. Pfeiffer.

PMID- 23008360
TI  - The transcervical expulsion of a large fibroid.
AB  - A 46-year-old woman presented to the emergency gynaecology unit at the Royal Free
      Hospital, London, with lower abdominal pain and offensive per vagina discharge.
      These symptoms developed following a recent uterine artery embolisation around 3
      weeks earlier at the same hospital. After initial treatment with antibiotics,
      this patient re-presented with a fibroid which had prolapsed through the cervix,
      resulting in pain, distress and more profuse vaginal discharge. This necrotic
      fibroid was morcellated and removed in theatre. She made an uneventful recovery
      and was able to go home the following day.

PMID- 23008361
TI  - Digoxin--'a friend or foe'.
AB  - The authors report about a patient who was admitted after developing nausea,
      vomiting, change in vision and lethargy. She was on digoxin 250 mcg once daily
      among all her other medications in the wake of a recent stroke that was
      accompanied by atrial fibrillation (AF). Her digitalis levels shortly before and
      on admission were 3.4 and 2.9 ng/ml, respectively. Her admission rhythm was
      slowly conducted AF at an average of 35 bpm. After a careful assessment by the
      cardiology consultant in charge, she received Digibind infusion for a chronic
      digitalis toxicity with the digoxin immune Fab dose based on the formula
      recommended in the product literature.(3) A few days observation on the ward
      ensured that her resting heart rate rose to 65 bpm and that she did not need a
      pacemaker for a slow AF. Her functional status remained reasonably good as she
      enjoyed a satisfactory recovery postthrombolysis for her recent stroke.

PMID- 23008362
TI  - Coronary artery stenting in a patient with chronic immune thrombocytopenic
      purpura: a clinical conundrum.
AB  - A patient with long-standing immune thrombocytopenic purpura (ITP) would
      logically contradict antiplatelet use due to increased bleeding risk during
      coronary stenting. Coronary stenting using an endothelial progenitor cells (EPC)
      capture stents (GenousTM) was used to successfully revascularise our patient
      using a transradial approach. The only complication was extensive superficial
      ecchymosis on the patient's forearm from antiplatelet use, which resolved
      spontaneously. To the best of our knowledge, this is the first case report of EPC
      capture stents in a chronic ITP patient.

PMID- 23008363
TI  - Warfarin improved CT values of the coronary artery artherosclerotic plaque:
      evaluation by 64-MDCTA.
AB  - 64-multidetector CT angiography (MDCTA) can identify plaques and assess different
      plaque components (lipid, fibrous tissue and calcifications). The first patient
      was a 75-year-old-man with atrial fibrillation (AF). Axial 64-MDCTA image of a
      coronary artery atherosclerotic plaque was obtained, which included the plaque on
      the outer vessel wall. The authors measured the five points of CT values around
      the vague center of the plaque with almost equal interval, which was shown in
      figure 1. Max was 80 Hounsfield unit (HU), and min was 28 HU. After 3 months
      warfarin therapy (1.5 mg id), max increased to 100 HU, and min increased to 69
      HU. The second patient was a 74-year-old-male with hypertension and AF. Max was
      61 HU, and min was 37 HU. After 3 months warfarin therapy (2.5 mg id), max
      increased to 70 HU, and min increased to 50 HU. Warfarin increased CT values of
      the artherosclerotic plaques in two patients with AF.

PMID- 23008364
TI  - Indirect carotid-cavernous fistula following minor head trauma treated with
      incomplete radiographic endovascular occlusion.
AB  - We report the unusual case of a patient with an indirect carotid-cavernous
      fistula treated with only partial angiographic embolisation of the fistula;
      however, by 8 weeks postembolisation, she was found to have both symptomatic and
      angiographic cure. This case highlights the potential for treating indirect
      carotid-cavernous fistulas with partial embolisation as a means of achieving
      angiographic and symptomatic cure by altering flow dynamics to attain spontaneous
      thrombosis.

PMID- 23008365
TI  - A bony swelling on the forehead: an uncommon manifestation of a well-known
      metabolic disease.

PMID- 23008366
TI  - An unusual case of chronic urinary retention and bladder diverticulum presenting
      with unilateral lower limb swelling.
AB  - A 64-year-old man presented with 1 month of gradual-onset left leg swelling and
      lower urinary tract symptoms including enuresis, frequency and poor stream. He
      was initially treated for suspected cellulitis, however, he returned 2 weeks
      later with persistence of his symptoms. Routine biochemical investigation
      revealed renal failure (Cr 623, Ur 29.9) and hyperkalaemia (K 7.2). Abdominal
      examination revealed a distended urinary bladder and an ultrasound scan revealed
      hydronephrosis, confirming the diagnosis of chronic high-pressure urinary
      retention. A urinary catheter was passed that initially drained 1.5 litre of
      clear urine. Shortly after insertion, this became heavily blood stained. A CT
      kidney ureter bladder (CTKUB) revealed a large mass behind the bladder thought to
      represent either an abscess or tumour. Cystoscopic correlation showed this to be
      a large, narrow-necked bladder diverticulum tensely distended with clot.
      Following successful clot evacuation and decompression of the bladder the leg
      swelling resolved and renal function improved.

PMID- 23008367
TI  - Change in striatal metabolism in diabetic haemichorea-haemiballism.
AB  - We studied metabolic changes in relation to chorea in two patients with diabetic
      haemichorea-haemiballism using positron emission tomography with (18)F
      fluorodeoxyglucose. Metabolism of the striatum and globus pallidus did not change
      in the acute choreic stage, but it decreased in the later stage after the
      amelioration of chorea. Striatal and pallildal hypometabolism in the late stage
      in diabetic haemichorea-haemiballism may reflect tissue ischaemia with gliosis.
      Previous studies have demonstrated striatal hypometabolism in neurodegenerative
      choreic disorders and striatal hypermetabolism in acute inflammatory choreic
      disorders. Previous findings as well as our results suggest that striatal and
      pallidal metabolic changes may be correlated with histological changes more than
      with functional changes relevant to chorea.

PMID- 23008368
TI  - A mesenteric hernia complicated with a triple necrotic volvulus.
AB  - A 6-year-old girl was admitted to the paediatric emergency department with
      colicky abdominal pain. She had a significant medical history, with four previous
      admissions due to recurrent abdominal pain in the past year. On examination the
      abdomen was soft, there was no rebound tenderness and Rovsing's sign was
      negative. Her blood tests revealed a raised white cells count, although her C
      reactive protein was within the normal range. Abdominal x-ray revealed small
      bowel obstruction. During her assessment the patient rapidly deteriorated and
      seemed to go into shock. Her clinical state in addition to the radiological
      findings meant that she was taken to theatre for surgical exploration. This
      showed a triple volvulus with necrotic bowel loops that had herniated through a
      mesenteric defect. The necrotic bowel was subsequently resected.

PMID- 23008369
TI  - Candida glabrata: an unusual fungal infection following a total hip replacement.
AB  - A 60-year-old woman, after a femoral neck fracture and joint replacement,
      underwent a Girdlestone's procedure and received aggressive antimicrobial therapy
      in order to completely eradicate the fungal infection Candida glabrata. In the
      majority of such cases, a revised hip arthroplasty would be considered following
      debridement. However, due to the recurrence of this infection and a key
      associated risk factor, radical removal with concurrent drug therapy was the only
      option.

PMID- 23008370
TI  - Recurrent febrile respiratory distress in infant: which diagnosis?
AB  - Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare
      congenital anomaly. CCAM diagnosis can be made by prenatal ultrasound or in
      postnatal cases with regard to respiratory distress or recurrent respiratory
      infections. We present, for diagnostic purposes, a case of a patient, aged 4
      months who had suffered since birth from recurrent bronchopulmonary infections.
      He was hospitalised several times for febrile respiratory distress. Chest x-rays
      previously performed were interpreted as normal. A final radiograph indicated the
      diagnosis and it was confirmed by CT. Surgical resection was performed with a
      positive result. CCAM responds to the prenatal diagnosis and requires frequent
      ultrasound checks during pregnancy and allowing for optimal management. The
      radiological assessment leads to the diagnosis and addresses the treatment which
      is based on a surgical cure.

PMID- 23008371
TI  - Can you be too premature to develop pyloric stenosis?
AB  - Diagnosis of Pyloric stenosis is rare in preterm babies. A case of pyloric
      stenosis diagnosed at 33(+6) postmenstrual age is reported. To our knowledge,
      this is the youngest postmenstrual age in the literature for a preterm infant to
      have a confirmed diagnosis of pyloric stenosis. The report also discusses issues
      that could delay the diagnosis of this condition in this patient population.

PMID- 23008372
TI  - Large liquefaction of lymph nodes during tuberculosis-associated immune
      reconstitution inflammatory syndrome in an HIV-infected woman.

PMID- 23008373
TI  - Primary malignant lymphoma of the uterine cervix.
AB  - Primary malignant lymphoma of the female genital tract is an extremely rare
      clinical entity. We report a case of primary non-Hodgkin lymphoma of the uterine
      cervix. An 85-year-old woman presented with abnormal genital bleeding. A
      colposcopic examination revealed a mass in the uterine cervix. No other lesions
      were detected by the whole-body CT, gallium scintigraphy and bone marrow
      examination. The histological examination and immunohistochemical staining of the
      cervical biopsy material confirmed a diagnosis of diffuse large B cell lymphoma
      of the uterine cervix, clinical stage 1E (according to the Ann Arbor Staging
      Classification for Lymphomas). The patient was treated with rituximab,
      cyclophosphamide, hydroxydaunorubicin, vincristine (oncovin) and prednisone. Her
      family refused surgery and involved field irradiation. She was in good condition
      but after 5 months she expired due to myocardial infarction.

PMID- 23008374
TI  - Duodenal perforation secondary to migration of endobiliary prosthesis.
AB  - A 27-year-old woman presented to the emergency department with abdominal pain,
      four days post endoscopic retrograde cholangiopancreatography (ERCP) and
      insertion of an endobiliary stent. A plain abdominal film highlighted the stent
      in an atypical position within the abdomen. As such, the patient progressed to a
      CT scan, confirming a retroperitoneal perforation of the duodenum by the stent.
      Laparotomy returned the stent to the duodenum with a primary duodenal repair.
      This case highlights the high index of suspicion required in patients who present
      with acute abdominal pain post-ERCP.

PMID- 23008375
TI  - Successful resection of complicated bleeding arteriovenous malformation of the
      jejunum in patients starting dual-antiplatelet therapy just after implanting a
      drug-eluting coronary stent.
AB  - We report a case of a 57-year-old man who started dual-antiplatelet therapy with
      aspirin and clopidogrel following implantation of drug-eluting coronary stent and
      developed persistent active gastrointestinal bleeding. After detecting the origin
      of bleeding by double-balloon enteroscopy, successful laparoscopy-assisted
      partial jejunal resection was performed and the patient condition was promptly
      recovered, without any thrombotic or bleeding complications. Pathology revealed
      arteriovenous malformation of the jejunum without any malignancy. We should care
      for and be aware of this lesion as a rare cause of gastrointestinal bleeding when
      strong antithrombotic therapy is initiated. Under rigorous assessment and
      perioperative management, as well as meticulous intraoperative dissection and
      haemostasis, satisfactory outcome was achieved even in this complicated
      situation.

PMID- 23008376
TI  - Large left atrial myxoma with an unusual origin.

PMID- 23008377
TI  - Spastic foot-drop as an isolated manifestation of neurocysticercosis.
AB  - Foot-drop is a rare but important manifestation of intracranial pathologies
      ranging from space-occupying lesions to cerebrovascular accidents. Being most
      commonly associated with peripheral nerve lesions or radicular compressions, it
      remains an underappreciated feature of central-structural abnormalities. We
      describe an interesting case of a 14-year-old boy who had presented with acute
      onset right-sided foot-drop due to a left-sided parasagittal neurocysticercus
      lesion, without seizures and discuss the location of the lesion in the precentral
      area in reference to Penfield's motor homunculus.

PMID- 23008378
TI  - Gigantic unruptured sinus of Valsalva aneurysm presenting as an incidental
      murmur.
AB  - We report a case of a 56-year-old man referred by his family physician with an
      asymptomatic cardiac murmur. Trans-thoracic echocardiography (TTE) suggested an
      unruptured right sinus of Valsalva aneurysm (SVA) causing extrinsic compression
      of the right ventricular outflow tract. This was confirmed with an ECG-gated
      cardiac CT showing a large right SVA measuring 35*37*42 mm in size. Coronary
      angiography demonstrated non-obstructive coronary artery disease. Ascending
      thoracic anterior in the right anterior oblique view delineated the right SVA.
      The patient underwent aortic valve sparing surgical repair of the aneurysm with
      an excellent result. Echocardiography confirmed obliteration of the aneurysm and
      normal aortic valve function postoperatively.

PMID- 23008379
TI  - Trapdoor ischaemia: coronary ostial occlusion by an aortic dissection.
AB  - We present an interesting case of an elderly man with acute myocardial infarction
      due to retrograde dissection of the aortic root occluding the coronary ostia.

PMID- 23008380
TI  - Survival over 6 years in a patient with brain metastases from melanoma treated
      with temozolomide.
AB  - Cerebral metastases from melanoma are generally associated with a dismal
      prognosis with survival ranging from 3 to 6 months after treatment. Systemic
      chemotherapy for these patients has limited effect and evidence for an overall
      survival benefit from randomised controlled trials is lacking. We report on a 59
      year-old patient with a history of malignant melanoma who presented with multiple
      cerebral metastases after previous surgery and combined whole brain and
      stereotactic radiotherapy. She has been in sustained remission and in excellent
      clinical condition after treatment with continued cycles of oral temozolomide for
      more than 6 years. To our knowledge, similar prolonged survival has been
      described only once in patients with multiple cerebral metastases from melanoma.
      This case demonstrates that temozolomide for metastatic central nervous system
      (CNS) disease in melanoma patients may be highly effective without CNS toxicity.

PMID- 23008382
TI  - Neuroimaging markers of hemorrhagic risk with stroke reperfusion therapy.
AB  - OBJECTIVE: We sought to identify pretreatment neuroimaging markers associated
      with intracerebral hemorrhage (ICH) after reperfusion therapy for acute ischemic
      stroke. METHODS: A literature review using available online medical literature
      databases was performed to identify noninvasive imaging markers correlated with
      ICH after reperfusion therapy. Key words, including different neuroimaging
      modalities such as noncontrast CT, multimodal CT, and MRI techniques, were
      queried. The review included randomized, controlled trials, post hoc studies, and
      institutional registries. Studies of IV as well as intra-arterial reperfusion
      therapies were considered. Articles were organized on the basis of imaging
      modality and type of treatment. Each imaging modality was given 1 of 3 grades for
      consideration of use in clinical practice (grade 1: a modality whose use for
      hemorrhage prediction is supported by randomized controlled trials or post hoc
      studies from prospective trials; grade 2: a modality that is largely available
      but requires further prospective validation; and grade 3: a modality which is
      rarely used and has limited clinical utility). RESULTS: Grade 1 imaging
      modalities included the size of infarction as seen on noncontrast CT or diffusion
      MRI. Higher hemorrhagic risk has been seen with larger infarctions, suggesting
      that these imaging modalities may be effective screening tests to exclude
      specific patients. Perfusion imaging using CT or MRI was considered to have a
      grade 2 recommendation, pending further validation. The use of xenon CT,
      radionuclide imaging, voxel-based MRI analysis, and blood-brain barrier
      disruption imaging still require further design improvements (grade 3).
      CONCLUSIONS: Future reperfusion trials require clearly defined protocols for
      imaging and determination of symptomatic ICH. Future trials may consider the use
      of perfusion imaging and the inclusion of patients without large territorial
      infarctions to accurately predict those at risk for ICH with reperfusion therapy.

PMID- 23008381
TI  - Acute transverse myelitis following Japanese encephalitis viral infection: an
      uncommon complication of a common disease.
AB  - Japanese encephalitis (JE) is an epidemic encephalitis characterised by altered
      sensorium, convulsions, headache, brainstem signs with pyramidal and
      extrapyramidal features. Immune-mediated manifestation as acute transverse
      myelitis (ATM) has not been previously reported in JE. We describe a 40-year-old
      man who presented with an acute onset quadriparesis with urinary retention, which
      was preceded by fever and headache 3 weeks prior. He had elevated IgM titres
      against JE virus in serum and cerebrospinal fluid. MRI of cervico-thoracic spine
      demonstrated signal intensity alterations extending from C1 to D10 spinal
      segments. The patient was treated with intravenous methyl prednisolone for 5
      days. He regained normal power at 6 months follow-up and repeat MRI study
      demonstrated complete resolution of the lesion. We conclude that in a case of JE,
      one should be vigilant for early diagnosis of possible complication as ATM, in
      which an early institution of immunomodulator therapy prevents adverse
      consequences.

PMID- 23008383
TI  - How well do blood flow imaging and collaterals on angiography predict brain at
      risk?
AB  - As endovascular therapy emerges as a principal approach to restore blood flow in
      the setting of acute stroke, better methods of patient selection need to be
      developed. Noninvasive studies of blood flow and angiographic results acquired
      prior to endovascular therapy may help determine areas of brain at risk of
      infarction and hemorrhagic transformation, both largely determined by the
      severity of cerebral ischemia. Pathophysiologic measures of collateral flow and
      perfusion that characterize ischemic severity prior to revascularization may
      optimize acute stroke decision-making, currently driven by arbitrary time
      parameters derived from population studies devoid of imaging.

PMID- 23008385
TI  - Timing, testing, and standardization of endovascular therapy.

PMID- 23008384
TI  - Revascularization grading in endovascular acute ischemic stroke therapy.
AB  - BACKGROUND: Recanalization and angiographic reperfusion are key elements to
      successful endovascular and interventional acute ischemic stroke (AIS) therapy.
      Intravenous recombinant tissue plasminogen activator (rt-PA), the only
      established revascularization therapy approved by the US Food & Drug
      Administration for AIS, may be less effective for large artery occlusion. Thus,
      there is enthusiasm for endovascular revascularization therapies, which likely
      provide higher recanalization rates, and trials are ongoing to determine clinical
      efficacy and compare various methods. It is anticipated that clinical efficacy
      will be well correlated with revascularization of viable tissue in a timely
      manner. METHOD: Reporting, interpretation, and comparison of the various
      revascularization grading methods require agreement on measurement criteria,
      reproducibility, ease of use, and correlation with clinical outcome. These
      parameters were reviewed by performing a Medline literature search from 1965 to
      2011. This review critically evaluates current revascularization grading systems.
      RESULTS AND CONCLUSION: The most commonly used revascularization grading methods
      in AIS interventional therapy trials are the thrombolysis in cerebral ischemia
      (TICI, pronounced "tissy") and thrombolysis in myocardial ischemia (TIMI) scores.
      Until further technical and imaging advances can incorporate real-time reliable
      perfusion studies in the angio-suite to delineate regional perfusion more
      accurately, the TICI grading system is the best defined and most widely used
      scheme. Other grading systems may be used for research and correlation purposes.
      A new scale that combines primary site occlusion, lesion location, and perfusion
      should be explored in the future.

PMID- 23008386
TI  - Advances in thrombolytics for treatment of acute ischemic stroke.
AB  - Over the past 50 years, thrombolytic agents have been devised with the aim of
      recanalizing occluded coronary vessels, and later on, applied in the setting of
      acute ischemic stroke. Pharmacologic agents have generally targeted the
      plasminogen-plasmin transformation, facilitating the natural process of
      fibrinolysis. Newer agents with varying degrees of fibrin selectivity and
      pharmacologic half-life have influenced both recanalization rates and hemorrhagic
      complications, inside and outside the CNS. Intra-arterial (IA) administration of
      fibrinolytic agents increases delivery of the drug to the thrombus at a higher
      concentration with smaller quantities and therefore lowers systemic exposure.
      Mechanical thrombus disruption or extraction allows for drug delivery to a
      greater surface area of the thrombus. Delays associated with IA therapy may
      worsen the risk/benefit ratio of thrombolysis; therefore, combinations of IA-IV
      treatments have been studied. To date, there are no direct comparative trials to
      show that endovascular administration is more efficacious or carries a lower risk
      of hemorrhagic complications than IV tissue plasminogen activator.

PMID- 23008387
TI  - Merci mechanical thrombectomy retriever for acute ischemic stroke therapy:
      literature review.
AB  - BACKGROUND: Mechanical thrombectomy is a promising adjuvant or stand-alone
      therapy for acute ischemic stroke (AIS) caused by occlusion of a large vessel in
      patients beyond the systemic thrombolysis therapeutic window. This review focuses
      on the clinical and angiographic outcomes of mechanical thrombectomy with use of
      the Merci retriever device. METHODS: Available literature published to date on
      the major trials and observational studies involving the Merci retriever was
      reviewed. In addition to the review, results from studies involving the Merci
      retriever were compared to results from Prolyse in Acute Cerebral Thromboembolism
      II (PROACT II) and the Penumbra device studies. The predictors for favorable
      outcome following revascularization with the Merci device were reviewed on the
      basis of published stratified analyses. Favorable clinical outcome was defined in
      the Merci experience by a modified Rankin Scale (mRS) score of <= 2 at 90 days
      following AIS. RESULTS: Presented in this review are a total of 1,226 patients
      treated with the Merci device; 305 patients are from 2 pivotal trials involving
      the device, and the remaining 921 patients are from observational studies in the
      Merci registry. The 90-day mRS of <= 2 was achieved in 32% of the patient group,
      with an overall mortality rate of 35.2%. Symptomatic intracerebral hemorrhage was
      identified in 7.3% of patients treated with Merci retriever, a result comparable
      to that in the PROACT II and Penumbra thrombectomy trials. Successful
      recanalization, lower NIH Stroke Scale score, and younger age were identified as
      the strongest predictors of favorable outcomes. CONCLUSION: Mechanical
      thrombectomy with the Merci retriever device is a safe treatment modality for AIS
      patients presenting with a large-vessel occlusion within 8 hours of symptom
      onset. Although the Merci retriever showed a good recanalization rate, there are
      currently no randomized clinical trials to assess its clinical efficacy in
      comparison with systemic thrombolysis within a window of 3 to 4.5 hours or with
      standard of care beyond a 4.5-hour window.

PMID- 23008388
TI  - The Penumbra system for mechanical thrombectomy in endovascular acute ischemic
      stroke therapy.
AB  - BACKGROUND: Efficacy of IV systemic thrombolysis is limited in patients with
      severe acute ischemic stroke and large-vessel occlusion. Mechanical thrombectomy
      has been the mainstay therapy in large-vessel occlusion. This review focuses on
      the Penumbra aspiration device. METHOD: Literature review. RESULTS: The Penumbra
      prospective studies were reviewed and results are presented. The pivotal single
      arm prospective trial that led to its approval by the US Food and Drug
      Administration enrolled 125 patients within 8 hours of symptom onset and
      demonstrated an 82% recanalization rate, to Thrombolysis in Myocardial Ischemia
      (TIMI) scores of 2 and 3. The risk of symptomatic intracranial hemorrhage was
      10%, and modified Rankin Scale (mRS) score of <= 2 was 25%. In the postmarketing
      registry, 157 vessels were treated, with 87% achieving TIMI 2 and 3
      recanalization and 41% having an mRS score of <= 2. CONCLUSION: The Penumbra
      aspiration system is an effective tool to safely revascularize large-vessel
      occlusions in patients within 8 hours of onset of acute ischemic stroke who are
      either refractory to or excluded from IV thrombolytic therapy. Further
      prospective, randomized controlled trials will be needed to address whether this
      ability translates into neurologic improvement and better functional outcomes for
      our patients.

PMID- 23008389
TI  - Angioplasty and stenting for mechanical thrombectomy in acute ischemic stroke.
AB  - A large number of patients presenting with acute ischemic stroke have large
      artery intracranial occlusions, and timely recanalization of these occlusions
      often leads to improved neurologic outcome. Starting with the widespread use of
      IV tissue plasminogen activator, a wide variety of pharmacologic and mechanical
      methods have been introduced to improve vessel recanalization and clinical
      outcome of patients with acute ischemic stroke, which include endovascular
      therapies such as intra-arterial thrombolytics and mechanical thrombectomy
      devices. One of the potential therapies is angioplasty and stenting, and this has
      been evaluated in multiple case reports and small series published by various
      centers regarding its use in this setting. In this article, we review the current
      literature on stenting with and without angioplasty, used alone or as a part of
      multimodal therapy for recanalization for acute cerebrovascular occlusions.

PMID- 23008390
TI  - Retrievable stents, "stentrievers," for endovascular acute ischemic stroke
      therapy.
AB  - Endovascular therapy for acute ischemic stroke continues to evolve to improve
      both efficacy and safety. In the late 1990 s, intra-arterial chemical
      thrombolysis with prourokinase was shown to be effective in achieving partial
      recanalization and improving clinical outcome, in comparison with intra-arterial
      heparin administration. However, this was at the expense of an increase in the
      rate of symptomatic intracranial hemorrhage to 10%. To improve the rate of
      recanalization, expand the time window, and reduce the risk of symptomatic
      intracranial hemorrhage, mechanical thrombectomy was introduced, with initial
      approval of the Merci clot retriever, a corkscrew-like device, and then more
      recently with approval of the Penumbra thromboaspiration system. Both devices are
      associated with a high rate of recanalization (total, partial, and complete).
      However, time to recanalization was on average 45 minutes, with a low rate of
      complete clot resolution, given that the majority of patients achieved only
      partial recanalization. More recently, retrievable stents have shown promise in
      reducing the time to recanalization, and they achieve a higher rate of complete
      clot resolution with improved feasibility. The retrievable stent can be opened
      within the clot to engage it within the stent struts, and subsequently it is
      retrieved by pulling it under flow arrest. The retrievable stents provide a new
      tool in the armamentarium of devices that can be used to achieve safe and timely
      clot removal. This review provides the historical evolution of endovascular
      therapy to use of stentreivers.

PMID- 23008391
TI  - Endovascular therapy in children with acute ischemic stroke: review and
      recommendations.
AB  - This review provides a summary of the currently available data pertaining to the
      interventional management of acute ischemic stroke in children. The literature is
      scarce and is lacking much-needed prospective trials. No study in the literature
      on the well-established systemic or local thrombolysis trials has included
      children. Mechanical thrombectomy trials using clot retriever devices have also
      excluded patients younger than 18 years. The current review is limited to case
      series of interventional acute ischemic stroke therapy in children and the
      potential future of endovascular ischemic stroke therapy in this patient
      population. Recommendations in this review represent the opinion of the authors,
      based on review of the limited literature covering endovascular acute ischemic
      stroke therapy in children.

PMID- 23008392
TI  - Cost-effectiveness of endovascular therapy for acute ischemic stroke.
AB  - Though rarely considered in the clinical decision algorithm, issues of cost
      effectiveness assume critical importance for the sustainability of a widely used
      therapy that entails considerable cost and has unproven benefit. Although current
      data are limited, we review the studies that have demonstrated via modeling that
      endovascular stroke treatment may generate significant future economic benefits,
      even if these treatments have a high price and result in relatively small initial
      reductions in disability. We highlight important considerations that, on the
      basis of the logistics and protocols of current neuroendovascular practices,
      should be included in future cost-effectiveness analyses of endovascular therapy
      for acute ischemic stroke.

PMID- 23008393
TI  - Periprocedural management of acute ischemic stroke patients undergoing
      endovascular therapy.

PMID- 23008394
TI  - Anesthesia for endovascular treatment of acute ischemic stroke.
AB  - The initial treatment of patients with acute ischemic stroke (AIS) focuses on
      rapid recanalization, which often includes the use of endovascular therapies.
      Endovascular treatment depends upon micronavigation of catheters and devices into
      the cerebral vasculature, which is easier and safer with a motionless patient.
      Unfortunately, many stroke patients are unable to communicate and sufficiently
      cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal
      intubation provides an attractive means of keeping the patient comfortable and
      motionless during a procedure that could otherwise be lengthy and uncomfortable.
      However, several recent retrospective studies have shown an association between
      GA and poorer outcomes in comparison with conscious sedation for endovascular
      treatment of AIS, though prospective studies are lacking. The underlying reasons
      why GA might produce a worse outcome are unknown but may include hemodynamic
      instability and hypotension, delays in treatment, prolonged intubation with or
      without neuromuscular blockade, or even neurotoxicity of the anesthetic agent
      itself. Currently, the choice between GA and conscious sedation should be
      tailored to the individual patient, on the basis of neurologic deficits, airway
      and hemodynamic status, and treatment plan. The use of institutional treatment
      protocols may best support efficient and effective care for AIS patients
      undergoing endovascular therapy. Important components of such protocols would
      include parameters to choose anesthetic modality, timeliness of induction, blood
      pressure goals, minimization of neuromuscular blockade, and planned extubation at
      the end of the procedure.

PMID- 23008395
TI  - Periprocedural antithrombotic strategies in acute ischemic stroke interventional
      therapy.
AB  - In patients undergoing endovascular therapy for acute ischemic stroke,
      antithrombotic therapies are utilized to prevent distal embolization, arterial
      reocclusion, or catheter-related embolism. However, this must be weighed against
      the risk of hemorrhagic complications secondary to existing and ongoing ischemia
      or silent vessel perforation. In this article, we present an overview of the
      available literature evaluating antithrombotic therapy in patients undergoing
      endovascular therapy for acute ischemic stroke and discuss the emerging role of
      these agents.

PMID- 23008396
TI  - Periprocedural management of acute ischemic stroke intervention.
AB  - Periprocedural medical management is an important aspect in optimizing the
      outcome of patients who undergo endovascular treatment for acute ischemic stroke.
      Blood pressure, fluid hydration, and antithrombotics are some of the elements
      that need to be tailored carefully to the patient according to the patency of his
      or her cerebral vasculature, the extent of his or her infarct, and the potential
      for hemorrhagic transformation. This article reviews the medical care of acute
      stroke patients before and after endovascular therapy.

PMID- 23008397
TI  - Complications of endovascular therapy for acute ischemic stroke and proposed
      management approach.
AB  - Over the past decade, endovascular therapy has emerged as a promising therapeutic
      approach for select patients with acute ischemic stroke. However, the morbidity,
      mortality, and complication rates in intra-arterial recanalization trials are
      higher than in the National Institute of Neurological Disorders and Stroke trial
      of IV tissue plasminogen activator. This review discusses common complications
      associated with endovascular therapy for acute ischemic stroke, avoidance of
      complications, and management of some of the common complications.

PMID- 23008398
TI  - Neurocritical care and periprocedural blood pressure management in acute stroke.
AB  - The purpose of this article is to review the literature on periprocedural blood
      pressure (BP) management in acute ischemic stroke and to establish guidelines
      regarding management of BP. These guidelines are drawn from available evidence
      and expert opinion. This article reviews the pathophysiologic considerations of
      BP in ischemic stroke. It also examines the natural history of BP changes during
      stroke, as well as data on induced BP reduction and hypertension, particularly in
      light of reperfusion therapy. Finally, the article reviews major ongoing clinical
      trials for BP management in this setting. Recommendations made in this article
      may serve as a benchmark for future research in BP management in this patient
      population.

PMID- 23008399
TI  - The endovascular journey.

PMID- 23008400
TI  - Stem cell therapy in ischemic stroke: role of IV and intra-arterial therapy.
AB  - OBJECTIVE: Cell-based therapies are being investigated as an adjunct to IV
      thrombolysis or mechanical thrombectomy in ischemic stroke. This review
      summarizes the potential applications as well as challenges of intravascular cell
      delivery in ischemic stroke. METHOD: We conducted a search of Medline as well as
      the clinicaltrials.gov Web site for all ongoing human clinical studies using stem
      cells in ischemic stroke patients. RESULT: The pros and cons of the various donor
      cell types and routes of cell delivery, including intravascular delivery, in
      ischemic stroke are discussed. In addition, the potential challenges in
      translation from bench to bedside, the optimal techniques for intravascular cell
      delivery, and an updated comprehensive list of ongoing clinical trials in
      ischemic stroke are highlighted. CONCLUSIONS: Stem cells have shown a promising
      role in ischemic stroke, in preclinical studies as well as initial pilot studies.
      Further studies are needed to assess intravascular cell therapy as a potential
      adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke.

PMID- 23008401
TI  - Past, present, and future of endovascular stroke therapies.
AB  - Endovascular therapy in the acute management of ischemic stroke has become more
      common with technologic advances, such as easier navigation into the intracranial
      circulation and improved treatment efficacy with the advent of revascularization
      devices. This select review outlines milestones in the application of
      endovascular therapy in acute ischemic stroke (AIS) and offers some insight into
      important factors influencing the future directions of endovascular AIS
      treatment. In particular, we discuss the evolution of endovascular devices for
      AIS and how ingenuity continues to offer novel treatments. With these advances,
      the future of endovascular AIS treatment is promising.

PMID- 23008402
TI  - Percentage of acute stroke patients eligible for endovascular treatment.
AB  - Endovascular treatment for acute ischemic stroke has the potential to
      substantially improve the outcome for select individual stroke patients. However,
      the impact of this treatment on a population scale is unknown. We reviewed the
      epidemiology of acute stroke presentation times to estimate the proportion of
      patients with ischemic stroke who may be eligible for intra-arterial treatment.
      Experience with IV thrombolysis suggests that time from symptom onset is likely
      to be among the major exclusion criteria for intra-arterial treatment. Studies
      reviewed suggest that between 5% and 13% of patients with ischemic stroke present
      in the commonly recommended intra-arterial treatment window of 3 to 6 hours.
      Because of clinical exclusion factors other than time, the proportion of stroke
      patients eligible for intra-arterial treatment is likely even lower than these
      estimates. Clinicians and researchers should consider this a modest proportion of
      eligible patients when planning future studies and creating referral networks for
      endovascular stroke treatment.

PMID- 23008404
TI  - Performance and training standards for endovascular acute ischemic stroke
      treatment.
AB  - Stroke is the third leading cause of death in the United States, Canada, Europe,
      and Japan. According to the American Heart Association and the American Stroke
      Association, there are now 750,000 new strokes that occur each year, resulting in
      200,000 deaths, or 1 of every 16 deaths, per year in the United States alone.
      Endovascular therapy for patients with acute ischemic stroke is an area of
      intense investigation. The American Stroke Association has given a qualified
      endorsement of intra-arterial thrombolysis in selected patients. Intra-arterial
      thrombolysis has been studied in 2 randomized trials and numerous case series.
      Although 2 devices have been granted FDA phase 3 approval with an indication for
      mechanical stroke thrombectomy, none of these thrombectomy devices has
      demonstrated efficacy for the improvement of patient outcomes. The purpose of the
      present document is to define what constitutes adequate training to perform
      neuroendovascular procedures in patients with acute ischemic stroke and what
      performance standards should be adopted to assess outcomes. These guidelines have
      been written and approved by multiple neuroscience societies that historically
      have been directly involved in the medical, surgical and endovascular care of
      patients with acute stroke. These organizations include the Neurovascular
      Coalition and its participating societies, including the Society of
      NeuroInterventional Surgery (SNIS), American Academy of Neurology (AAN), American
      Association of Neurological Surgeons/Cerebrovascular Section (AANS/CNS), and
      Society of Vascular & Interventional Neurology (SVIN).

PMID- 23008403
TI  - Clinical trial design for endovascular ischemic stroke intervention.
AB  - BACKGROUND: Randomized, double-blinded, placebo-controlled trials have
      significant impact on clinical practice. The ultimate goal of a clinical trial of
      therapy for acute ischemic stroke (AIS) is to compare 2 interventions. Challenges
      may include interventional therapy standardization, enrollment rate, patient
      selection, biases, data and safety monitoring, reporting, and financial and
      logistical support. METHOD: Selected randomized and single-arm prospective AIS
      trial designs. Clinical trial elements and their challenges are reviewed.
      Innovative designs and proposed recommendations to overcome some of the specific
      challenges and limitations are discussed. RESULTS: AIS therapy trials have
      specific challenges related to ethical issues, enrollment rate, outcome measures,
      limited time to treatment, efficacy, safety, and limited or variable operator
      experience with complex technology in a delicate end organ. Proposed suggestions
      for improving trial design include the following: incorporation of a lead-in
      phase; careful patient and outcome measure selection; historical, concurrent, or
      hybrid controls; open data access; and a Bayesian approach. An open data paradigm
      may facilitate creation of computerized prediction models for future trials
      (minimizing cost by decreasing sample size or providing futility analyses and
      directing resources to other trials). Collaborative, consortium, and network
      infrastructures may allow more effective and efficient study completion. Self
      learning, self-correcting trials with intrinsic flexibility to adapt may help
      future clinical trial design in AIS. CONCLUSION: The randomized clinical trial
      design in AIS endovascular therapy is challenging. Lead-in phases, careful
      patient selection, use of innovative outcome measures, control groups, and newer
      clinical trial design may enhance conduct of future trials, their validity, and
      their results.

PMID- 23008405
TI  - Endovascular comprehensive stroke center designation parameters.

PMID- 23008407
TI  - Overview of key factors in improving access to acute stroke care.
AB  - BACKGROUND: Despite recent advances in acute stroke therapy, only a small
      proportion of patients with acute ischemic stroke receive IV and endovascular
      revascularization therapies. This article provides an overview of factors
      influencing access to stroke therapy. METHODS: The key factors influencing access
      to stroke care highlighted during the Society of Vascular and Interventional
      Neurology (SVIN) roundtable meeting are summarized. Pertinent selected references
      on prehospital, hospital, and legislative and economic factors influencing access
      to stroke care, from the Medline database (between 1995 to 2011), are included. A
      brief summary of these key factors in improving access to stroke therapy is
      provided. RESULTS: Prehospital factors include the community; education of
      hospital administrators and health care personnel; dispatchers; the medical
      transport system; and preparedness and stroke education of emergency medical
      services (EMS). Stroke-ready hospitals and networking with other regional
      tertiary stroke hospitals play important roles in increasing access to stroke
      care. In addition, legislation at the state and federal levels is a key factor in
      providing high-quality, timely access to stroke care for the population in
      general. Strategies to facilitate access to stroke therapy are critical to
      improving mortality and functional outcome and increasing the proportion of
      patients treated by systemic thrombolysis and endovascular approaches.
      CONCLUSION: This is a brief overview and summary of selected factors influencing
      access to stroke care. These factors are divided into prehospital, hospital,
      legislative, and economic categories. Multilevel education of the population,
      public health care personnel, hospital preparedness, and legislative and economic
      factors are important in improving access to stroke care.

PMID- 23008406
TI  - Developing practice recommendations for endovascular revascularization for acute
      ischemic stroke.
AB  - Guidelines have been established for the management of acute ischemic stroke;
      however, specific recommendations for endovascular revascularization therapy are
      lacking. Burgeoning investigation of endovascular revascularization therapies for
      acute ischemic stroke, rapid device development, and a diverse training
      background of the providers performing the procedures underscore the need for
      practice recommendations. This review provides a concise summary of the Society
      of Vascular and Interventional Neurology endovascular acute ischemic stroke
      roundtable meeting. This document was developed to review current clinical
      efficacy of pharmacologic and mechanical revascularization therapy, selection
      criteria, periprocedure management, and endovascular time metrics and to
      highlight current practice patterns. It therefore provides an outline for the
      future development of multisociety guidelines and recommendations to improve
      patient selection, procedural management, and organizational strategies for
      revascularization therapies in acute ischemic stroke.

PMID- 23008408
TI  - Endovascular recanalization in acute ischemic stroke: regionalized organization
      of care.

PMID- 23008409
TI  - Demand-supply of neurointerventionalists for endovascular ischemic stroke
      therapy.
AB  - OBJECTIVE: To estimate the needed workforce of trained neurointerventionalists
      (NIs) to perform endovascular therapy (ET) for eligible patients with acute
      ischemic stroke (AIS). METHOD: Population and ischemic stroke incidence data were
      extracted with use of US Census and Centers for Disease Control and Prevention
      2009 estimates. The annual "demand" is defined as the proportion of AIS patients
      who would meet inclusion criteria and clinical standards for ET. The "supply" is
      defined as the number of trained NIs and NIs in training. The "workforce" is the
      number of NIs needed to meet the demand (the number of eligible AIS patients)
      within an accessible geographic diameter. Data on NIs and NI fellowships were
      collected (Society of Neurointerventional Surgery [SNIS], Society of Vascular &
      Interventional Neurology [SVIN], Concentric Medical, and Penumbra Inc.). RESULTS:
      The estimated number of NIs is close to 800, practicing within a 50-mile radius
      of major metropolitan areas in the United States, covering more than 95% of the
      US population. Approximately 40 NI fellows are graduating yearly from US training
      programs. In 5 years and 10 years, the number of NIs may reach 1,000 and 1,200,
      respectively. Currently, there are approximately 14,000 thrombectomy procedures
      performed in the United States each year. However, the percentage of AIS patients
      who may be eligible for ET in our estimation is 4% to 14%, or about 25,000 to
      95,000 patients. This means that cases will occur at a rate of 26 to 97 per year
      in 5 years, or 22 to 81 per year in 10 years, for each NI. Providing 24/7 AIS
      coverage requires 2 to 3 NIs per medical center, adding to the challenge of
      providing manpower without diluting experience in areas of lower population
      density. CONCLUSION: The current and projected number of NIs would adequately
      supply the future need if the proportion of patients requiring AIS endovascular
      therapy increases. However, 2 to 3 NIs per comprehensive stroke center would be
      needed to provide 24/7 AIS therapy with a sufficient number of cases per NI. A
      tertiary stroke center model similar to the trauma model may provide the manpower
      solution without compromising the quality of care.

PMID- 23008410
TI  - Endovascular acute ischemic stroke therapy: applying basic science to clinical
      decisions.

PMID- 23008411
TI  - Reperfusion brain injury: focus on cellular bioenergetics.
AB  - Energy production for the maintenance of brain function fails rapidly with the
      onset of ischemia and is reinstituted with timely reperfusion. The key
      bioenergetic organelle, the mitochondrion, is strongly affected by a cascade of
      events occurring with ischemia and reperfusion. Enhanced production of reactive
      oxygen species, disruption of calcium homeostasis, and an inflammatory response
      are induced by reperfusion and have a profound effect on cellular bioenergetics
      in reversible stroke. The impact of perturbed bioenergetics on cellular
      homeostasis/function during and after ischemia are discussed. Because
      mitochondrial function can be compromised by derangements at more than one of the
      susceptible sites on this organelle, we propose that a combination therapy is
      needed for the restoration and maintenance of cellular bioenergetics after
      reperfusion.

PMID- 23008412
TI  - Vascular neurologists and neurointerventionalists on endovascular stroke care:
      polling results.

PMID- 23008413
TI  - Blood-brain barrier, reperfusion injury, and hemorrhagic transformation in acute
      ischemic stroke.

PMID- 23008414
TI  - Role of the vascular endothelium and plaque in acute ischemic stroke.
AB  - The underlying cause of stroke lies in the damage to the arterial endothelial
      cell layer. The most profound damage is due to atherosclerosis, which can either
      occlude an artery or produce a thromboembolism. Diabetes and inflammation
      contribute to atherosclerosis and the associated endothelial damage by initiating
      and promoting the deposition of modified lipids in the subendothelium and by
      inhibiting endothelial nitric oxide (NO) production. At the same time, both
      production of endothelin-1 and generation of reactive oxygen species increase. In
      addition, leukocytes adhere to the endothelium and levels of C-reactive protein
      increase. The stroke that ensues upon cerebral artery occlusion or plaque rupture
      continues and exacerbates endothelial damage. Statins have been shown to be
      helpful in preventing stroke and diminishing its consequences. An international
      clinical trial to determine if an NO donor is effective (Efficacy of Nitric Oxide
      in Stroke study) is currently under way. Other interventions such as
      antioxidants, rho kinase inhibition, and endothelial progenitor cells offer
      promising avenues of research and perhaps therapeutic avenues for treatment of
      stroke. This article discusses the role of the vascular endothelium in ischemic
      stroke and those interventions that may provide plausible avenues for future
      therapy.

PMID- 23008415
TI  - Should clot composition affect choice of endovascular therapy?
AB  - Endovascular therapy has become a promising alternative for patients who are
      ineligible for IV thrombolysis or for whom it has failed. Greater knowledge about
      the composition of thromboembolic material underlying the vascular occlusion in
      stroke patients may provide the means for improving existing endovascular
      therapies and developing new treatment strategies. The objective of this article
      is to provide a review of clinical and experimental animal studies on the
      histology, imaging correlation, and ultrastructure of thromboemboli retrieved
      during acute ischemic stroke.

PMID- 23008416
TI  - Update on pharmacology of antiplatelets, anticoagulants, and thrombolytics.
AB  - Understanding of the pharmacology of thrombolytics, anticoagulants, and
      antiplatelets is critical to performing safe and effective endovascular therapy
      for acute ischemic therapy. This is a basic review of the clinical pharmacologic
      data on the anticoagulants, antiplatelets, and fibrinolytic agents most commonly
      used in the treatment of stroke and in the neurointerventional suite.

PMID- 23008417
TI  - Endovascular therapy and imaging: is a picture worth a thousand words?

PMID- 23008418
TI  - Identifying and utilizing the ischemic penumbra.
AB  - The penumbral concept is defined as different areas within the ischemic region
      evolve into irreversible brain injury over time and that this evolution is most
      critically linked to the severity of the decline in cerebral blood flow (CBF).
      The ischemic penumbra was initially defined as a region of reduced CBF with
      absent spontaneous or induced electrical potentials that still maintained ionic
      homeostasis and transmembrane electrical potentials. The reduction of CBF levels
      to between 10 and 15 mL/100 g/min and approximately 25 mL/100 g/min are likely to
      identify penumbral tissue, and the ischemic core of irreversible ischemic tissue
      has a CBF value below the lower threshold. The role of identifying this
      critically deprived brain tissue from CBF in triaging patients for endovascular
      ischemic therapy is evolving. In this review we focus on the basic science of the
      penumbral concept and identification using various imaging modalities (PET, MRI,
      and CT) in animal models and human studies. Another article in this supplement
      addresses the clinical implication and the current understanding and application
      of this concept into clinical practice of endovascular ischemic stroke therapy.

PMID- 23008419
TI  - Application of acute stroke imaging: selecting patients for revascularization
      therapy.
AB  - Due to the dynamic and versatile characteristics of ischemic penumbra, selecting
      the right acute ischemic stroke (AIS) patients for revascularization therapy (RT)
      based on initial available imaging can be challenging. The main patient selection
      criterion for RT is the size of the mismatch between the potentially salvageable
      tissue (penumbra) and the irreversibly damaged tissue (core). The goal of
      revascularization RT is to "freeze" the core and prevent it from extending to the
      penumbral tissue. Penumbral imaging selection of AIS patients for RT, using
      magnetic resonance or CT-based studies, may provide more clinical benefit to the
      appropriate patients, although direct evidence is pending. Not all penumbra-core
      mismatches beyond 3 hours are equal and need treatment, and defining which
      mismatches to target for RT is the current goal of ongoing clinical trials. In
      addition to "penumbral"-based imaging, large vessel occlusion and clot length
      estimation based on CT angiography and noncontrasted ultrathin CT scan has been
      used to identify patients who are refractory to systemic thrombolysis and may be
      eligible for endovascular therapy. The application of various imaging modalities
      in selecting and triaging AIS patients for RT is discussed in this review. Larger
      prospective randomized trials are needed to better understand the role of various
      imaging modalities in selecting AIS patients for RT and to understand its
      influence on clinical outcome.

PMID- 23008420
TI  - Use of neuroimaging to guide the treatment of patients beyond the 8-hour time
      window.
AB  - Revascularization time windows for patients with acute ischemic stroke are
      generally restricted to 8 hours. Later treatment attempts require more accurate
      prediction of risk and benefit, as safety and efficacy at these time strata are
      less well demonstrated. Advanced imaging techniques identify irreversible
      infarction as well as tissue at risk. Diffusion-weighted MRI detects ischemia
      within minutes of onset, whereas perfusion-weighted MRI and CT perfusion studies
      disclose the ischemic penumbra. Combined, they provide information on mismatched
      tissue-potentially salvageable brain. In addition, noninvasive angiography is a
      useful adjunct to localize arterial occlusion.

PMID- 23008421
TI  - Cloning and functional characterization of a gene for capsanthin-capsorubin
      synthase from tiger lily (Lilium lancifolium Thunb. 'Splendens').
AB  - The orange color of tiger lily (Lolium lancifolium 'Splendens') flowers is due,
      primarily, to the accumulation of two kappa-xanthophylls, capsanthin and
      capsorubin. An enzyme, known as capsanthin-capsorubin synthase (CCS), catalyzes
      the conversion of antheraxanthin and violaxanthin into capsanthin and capsorubin,
      respectively. We cloned the gene for capsanthin-capsorubin synthase (Llccs) from
      flower tepals of L. lancifolium by the rapid amplification of cDNA ends (RACE)
      with a heterologous non-degenerate primer that was based on the sequence of a
      gene for lycopene beta-cyclase (lcyB). The full-length cDNA of Llccs was 1,785 bp
      long and contained an open reading frame of 1,425 bp that encoded a polypeptide
      of 474 amino acids with a predicted N-terminal plastid-targeting sequence.
      Analysis by reverse transcription-PCR (RT-PCR) revealed that expression of Llccs
      was spatially and temporally regulated, with expression in flower buds and
      flowers of L. lancifolium but not in vegetative tissues. Stable overexpression of
      the Llccs gene in callus tissue of Iris germanica, which accumulates several
      xanthophylls including violaxanthin, the precursor of capsorubin, resulted in
      transgenic callus whose color had changed from its normal yellow to red-orange.
      This novel red-orange coloration was due to the accumulation of two non-native
      kappa-xanthophylls, capsanthin and capsorubin, as confirmed by HPLC and
      ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      analysis with authentic standards. Cloning of the Llccs gene should advance our
      understanding of the molecular and genetic mechanisms of the biosynthesis of
      kappa-carotenoids in general and in the genus Lilium in particular, and will
      facilitate transgenic alterations of the colors of flowers and fruits of many
      plant species.

PMID- 23008422
TI  - Florigenic and antiflorigenic signaling in plants.
AB  - The evidence that FLOWERING LOCUS T (FT) protein, and its paralog TWIN SISTER OF
      FT, act as the long-distance floral stimulus, or at least that they are part of
      it in diverse plant species, has attracted much attention in recent years.
      Studies to understand the physiological and molecular apparatuses that integrate
      spatial and temporal signals to regulate developmental transitions in plants have
      occupied countless scientists and have resulted in an unmanageably large amount
      of research data. Analysis of these data has helped to identify multiple systemic
      florigenic and antiflorigenic regulators. This study gives an overview of the
      recent research on gene products, phytohormones and other metabolites that have
      been demonstrated to have florigenic or antiflorigenic functions in plants.

PMID- 23008423
TI  - Association of myocardial deformation with outcome in asymptomatic aortic
      stenosis with normal ejection fraction.
AB  - BACKGROUND: Current guidelines recommend intervention for symptomatic aortic
      stenosis, but the management of asymptomatic aortic stenosis remains
      controversial. As left ventricular global longitudinal strain (GLS) has been
      shown to predict cardiovascular outcome, we sought to find whether its use could
      guide the assessment of risk in these patients. METHODS AND RESULTS: We
      prospectively followed 79 patients with severe asymptomatic aortic stenosis (39
      men; mean age, 77 +/- 12 years; aortic valve [AV] area index, 0.36 cm(2)/m(2)).
      In addition to standard echocardiography, speckle strain was measured to assess
      GLS. Patients were followed for cardiac death and AV replacement driven by
      symptom development. A multivariable Cox regression was performed to identify
      associations with events. During 23 +/- 20 months, 3 patients had cardiac death
      and 49 underwent AV replacement. Event-free survival was 72 +/- 5% at 1 year, 50
      +/- 5% at 2 years, and 24 +/- 5% at 4 years. Death and AV replacement were
      predicted by GLS (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]; P=0.037), as well
      as extent of AV calcification (HR, 2.44 [95% CI, 1.17-5.12]; P=0.018), peak
      transaortic pressure gradient (HR, 1.03 [95% CI, 1.01-1.04]; P<0.001), valvulo
      arterial impedance (HR, 1.32 [95% CI, 1.04-1.67]; P=0.045), and Society of
      Thoracic Surgeons Predicted Risk of Morbidity and Mortality (HR, 0.95 [95% CI,
      0.90-1.00]; P=0.052). A mean absolute GLS <15% was associated with a significant
      excess mortality, and this measurement added incremental prognostic value to the
      Society of Thoracic Surgeons Predicted Risk of Morbidity and Mortality,
      transaortic peak pressure gradient, AV calcification, and valvulo-arterial
      impedance. CONCLUSIONS: GLS is associated with outcomes in patients with severe
      asymptomatic aortic stenosis, incremental to other clinical and echocardiographic
      variables.

PMID- 23008424
TI  - From victim safety to victim engagement: comments on "The impact of victim
      focused outreach on criminal legal system outcomes following police-reported
      intimate partner abuse".

PMID- 23008425
TI  - Harmony or discord between victim agency and the criminal justice system: a
      comment on DePrince, Belknap, Labus, Buckingham, and Gover.

PMID- 23008426
TI  - The benefits of more "victim-focused" coordinated community responses to intimate
      partner violence: a critique of "The impact of victim-focused outreach on
      criminal legal system outcomes following police-reported intimate partner abuse,"
      by Anne P. DePrince, Joanne Belknap, Jennifer S. Labus, Susan E. Buckingham, and
      Angela R. Gover.

PMID- 23008428
TI  - The validation of the Checklist of Controlling Behaviors (CCB): assessing
      coercive control in abusive relationships.
AB  - The current study addresses the validation of the Checklist of Controlling
      Behaviors (CCB), an 84-item domestic violence assessment instrument that can be
      used to address multiple levels of violence and coercive control in violent
      relationships. Derived from clinical observation and current theories, the CCB
      makes use of intimate partner violence survivor reports to identify the intensity
      and frequency of relationship violence. The instrument is divided into 10
      subscales including (1) physical abuse, (2) sexual abuse, (3) male privilege, (4)
      isolation, (5) minimizing and denying, (6) blaming, (7) intimidation, (8)
      threats, (9) emotional abuse, and (10) economic abuse. To assess validity and
      reliability of the CCB, 2,135 female volunteers taking refuge at a domestic
      violence shelter were administered the instrument. Results of principal component
      analysis of the individual subscales revealed 10 factors having goodness-of-fit
      values above the desired normative level of .90.

PMID- 23008430
TI  - Lethal and non-lethal violence against women in Australia: measurement
      challenges, conceptual frameworks, and limitations in knowledge.
AB  - Understanding pathways from non-lethal violence to lethal violence between
      intimate partners is a notable challenge for both policy and practice in partner
      violence prevention. Of particular interest is whether lethal violence represents
      an "escalation" of violence from "low" to "high" risk over time, or is best
      predicted by specific behavioral "typologies" of perpetrators. Testing the
      "escalation" and "typology" theories is hampered in Australia by limitations in
      knowledge about non-lethal and lethal violence against women. This article
      discusses data limitations, measurement problems, and conceptual shortcomings,
      and suggests approaches to improving evidence quality in the field of violence
      prevention and risk assessment.

PMID- 23008429
TI  - Psychological distress and substance use among community-recruited women
      currently victimized by intimate partners: a latent class analysis and
      examination of between-class differences.
AB  - Latent class analysis was used to examine patterns of victimization among a
      community sample of 212 women experiencing intimate partner violence (IPV).
      Results identified three classes of women characterized by victimization history
      (recent IPV, childhood victimization); classes were further differentiated by IPV
      related posttraumatic stress disorder symptoms, other indicators of psychological
      distress, and substance use. Differentiating levels of victimization and their
      associated patterns of psychosocial functioning can be used to develop
      intervention strategies targeting the needs of different subgroups of women so
      that mental health and substance use problems can be reduced or prevented
      altogether. Implications for treatment and future research are presented here.

PMID- 23008431
TI  - Stretching and setting boundaries.

PMID- 23008432
TI  - Simulated annealing reveals the kinetic activity of SGLT1, a member of the LeuT
      structural family.
AB  - The Na(+)/glucose cotransporter (SGLT1) is the archetype of membrane proteins
      that use the electrochemical Na(+) gradient to drive uphill transport of a
      substrate. The crystal structure recently obtained for vSGLT strongly suggests
      that SGLT1 adopts the inverted repeat fold of the LeuT structural family for
      which several crystal structures are now available. What is largely missing is an
      accurate view of the rates at which SGLT1 transits between its different
      conformational states. In the present study, we used simulated annealing to
      analyze a large set of steady-state and pre-steady-state currents measured for
      human SGLT1 at different membrane potentials, and in the presence of different
      Na(+) and alpha-methyl-d-glucose (alphaMG) concentrations. The simplest kinetic
      model that could accurately reproduce the time course of the measured currents
      (down to the 2 ms time range) is a seven-state model (C(1) to C(7)) where the
      binding of the two Na(+) ions (C(4)->C(5)) is highly cooperative. In the forward
      direction (Na(+)/glucose influx), the model is characterized by two slow,
      electroneutral conformational changes (59 and 100 s(-1)) which represent
      reorientation of the free and of the fully loaded carrier between inside-facing
      and outside-facing conformations. From the inward-facing (C(1)) to the outward
      facing Na-bound configuration (C(5)), 1.3 negative elementary charges are moved
      outward. Although extracellular glucose binding (C(5)->C(6)) is electroneutral,
      the next step (C(6)->C(7)) carries 0.7 positive charges inside the cell.
      Alignment of the seven-state model with a generalized model suggested by the
      structural data of the LeuT fold family suggests that electrogenic steps are
      associated with the movement of the so-called thin gates on each side of the
      substrate binding site. To our knowledge, this is the first model that can
      quantitatively describe the behavior of SGLT1 down to the 2 ms time domain. The
      model is highly symmetrical and in good agreement with the structural information
      obtained from the LeuT structural family.

PMID- 23008433
TI  - High Ca(2+) permeability of a peptide-gated DEG/ENaC from Hydra.
AB  - Degenerin/epithelial Na(+) channels (DEG/ENaCs) are Na(+) channels that are
      blocked by the diuretic amiloride. In general, they are impermeable for Ca(2+) or
      have a very low permeability for Ca(2+). We describe here, however, that a
      DEG/ENaC from the cnidarian Hydra magnipapillata, the Hydra Na(+) channel
      (HyNaC), is highly permeable for Ca(2+) (P(Ca)/P(Na) = 3.8). HyNaC is directly
      gated by Hydra neuropeptides, and in Xenopus laevis oocytes expressing HyNaCs,
      RFamides elicit currents with biphasic kinetics, with a fast transient component
      and a slower sustained component. Although it was previously reported that the
      sustained component is unselective for monovalent cations, the selectivity of the
      transient component had remained unknown. Here, we show that the transient
      current component arises from secondary activation of the Ca(2+)-activated Cl(-)
      channel (CaCC) of Xenopus oocytes. Inhibiting the activation of the CaCC leads to
      a simple on-off response of peptide-activated currents with no apparent
      desensitization. In addition, we identify a conserved ring of negative charges at
      the outer entrance of the HyNaC pore that is crucial for the high Ca(2+)
      permeability, presumably by attracting divalent cations to the pore. At more
      positive membrane potentials, the binding of Ca(2+) to the ring of negative
      charges increasingly blocks HyNaC currents. Thus, HyNaC is the first member of
      the DEG/ENaC gene family with a high Ca(2+) permeability.

PMID- 23008434
TI  - Calcium buffering properties of sarcoplasmic reticulum and calcium-induced Ca(2+)
      release during the quasi-steady level of release in twitch fibers from frog
      skeletal muscle.
AB  - Experiments were performed to characterize the properties of the intrinsic Ca(2+)
      buffers in the sarcoplasmic reticulum (SR) of cut fibers from frog twitch muscle.
      The concentrations of total and free calcium ions within the SR ([Ca(T)](SR) and
      [Ca(2+)](SR)) were measured, respectively, with the EGTA/phenol red method and
      tetramethylmurexide (a low affinity Ca(2+) indicator). Results indicate SR Ca(2+)
      buffering was consistent with a single cooperative-binding component or a
      combination of a cooperative-binding component and a linear binding component
      accounting for 20% or less of the bound Ca(2+). Under the assumption of a single
      cooperative-binding component, the most likely resting values of [Ca(2+)](SR) and
      [Ca(T)](SR) are 0.67 and 17.1 mM, respectively, and the dissociation constant,
      Hill coefficient, and concentration of the Ca-binding sites are 0.78 mM, 3.0, and
      44 mM, respectively. This information can be used to calculate a variable
      proportional to the Ca(2+) permeability of the SR, namely d[Ca(T)](SR)/dt /
      [Ca(2+)](SR) (denoted release permeability), in experiments in which only
      [Ca(T)](SR) or [Ca(2+)](SR) is measured. In response to a voltage-clamp step to 
      20 mV at 15 degrees C, the release permeability reaches an early peak followed by
      a rapid decline to a quasi-steady level that lasts ~50 ms, followed by a slower
      decline during which the release permeability decreases by at least threefold.
      During the quasi-steady level of release, the release amplitude is 3.3-fold
      greater than expected from voltage activation alone, a result consistent with the
      recruitment by Ca-induced Ca(2+) release of 2.3 SR Ca(2+) release channels
      neighboring each channel activated by its associated voltage sensor. Release
      permeability at -60 mV increases as [Ca(T)](SR) decreases from its resting
      physiological level to ~0.1 of this level. This result argues against a release
      termination mechanism proposed in mammalian muscle fibers in which a luminal
      sensor of [Ca(2+)](SR) inhibits release when [Ca(T)](SR) declines to a low level.

PMID- 23008435
TI  - cAMP controls rod photoreceptor sensitivity via multiple targets in the
      phototransduction cascade.
AB  - In early studies, both cyclic AMP (cAMP) and cGMP were considered as potential
      secondary messengers regulating the conductivity of the vertebrate photoreceptor
      plasma membrane. Later discovery of the cGMP specificity of cyclic nucleotide
      gated channels has shifted attention to cGMP as the only secondary messenger in
      the phototransduction cascade, and cAMP is not considered in modern schemes of
      phototransduction. Here, we report evidence that cAMP may also be involved in
      regulation of the phototransduction cascade. Using a suction pipette technique,
      we recorded light responses of isolated solitary rods from the frog retina in
      normal solution and in the medium containing 2 uM of adenylate cyclase activator
      forskolin. Under forskolin action, flash sensitivity rose more than twofold
      because of a retarded photoresponse turn-off. The same concentration of forskolin
      lead to a 2.5-fold increase in the rod outer segment cAMP, which is close to
      earlier reported natural day/night cAMP variations. Detailed analysis of cAMP
      action on the phototransduction cascade suggests that several targets are
      affected by cAMP increase: (a) basal dark phosphodiesterase (PDE) activity
      decreases; (b) at the same intensity of light background, steady background
      induced PDE activity increases; (c) at light backgrounds, guanylate cyclase
      activity at a given fraction of open channels is reduced; and (d) the magnitude
      of the Ca(2+) exchanger current rises 1.6-fold, which would correspond to a 1.6
      fold elevation of [Ca(2+)](in). Analysis by a complete model of rod
      phototransduction suggests that an increase of [Ca(2+)](in) might also explain
      effects (b) and (c). The mechanism(s) by which cAMP could regulate [Ca(2+)](in)
      and PDE basal activity is unclear. We suggest that these regulations may have
      adaptive significance and improve the performance of the visual system when it
      switches between day and night light conditions.

PMID- 23008437
TI  - Educational and psychological interventions to improve outcomes for recipients of
      implantable cardioverter defibrillators and their families: a scientific
      statement from the American Heart Association.
AB  - Significant mortality benefits have been documented in recipients of implantable
      cardioverter defibrillators (ICDs); however, the psychosocial distress created by
      the underlying arrhythmia and its potential treatments in patients and family
      members may be underappreciated by clinical care teams. The disentanglement of
      cardiac disease and device-related concerns is difficult. The majority of ICD
      patients and families successfully adjust to the ICD, but optimal care pathways
      may require additional psychosocial attention to all ICD patients and
      particularly those experiencing psychosocial distress. This state-of-the-science
      report was developed on the basis of an analysis and critique of existing science
      to (1) describe the psychological and quality-of-life outcomes after receipt of
      an ICD and describe related factors, such as patient characteristics; (2)
      describe the concerns and educational/informational needs of ICD patients and
      their family members; (3) outline the evidence that supports interventions for
      improving educational and psychological outcomes for ICD patients; (4) provide
      recommendations for clinical approaches for improving patient outcomes; and (5)
      identify priorities for future research in this area. The ultimate goal of this
      statement is to improve the precision of identification and care of psychosocial
      distress in ICD patients to maximize the derived benefit of the ICD.

PMID- 23008436
TI  - Use-dependent block of the voltage-gated Na(+) channel by tetrodotoxin and
      saxitoxin: effect of pore mutations that change ionic selectivity.
AB  - Voltage-gated Na(+) channels (NaV channels) are specifically blocked by
      guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar
      to micromolar affinity depending on key amino acid substitutions in the outer
      vestibule of the channel that vary with NaV gene isoforms. All NaV channels that
      have been studied exhibit a use-dependent enhancement of TTX/STX affinity when
      the channel is stimulated with brief repetitive voltage depolarizations from a
      hyperpolarized starting voltage. Two models have been proposed to explain the
      mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion
      mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A,
      and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic
      selectivity and Ca(2+) permeability to test the trapped ion mechanism, which
      attributes use-dependent enhancement of toxin affinity to electrostatic repulsion
      between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel
      vestibule in the closed state. Our results indicate that TTX/STX use dependence
      is not relieved by mutations that enhance Ca(2+) permeability, suggesting that
      ion-toxin repulsion is not the primary factor that determines use dependence.
      Evidence now favors the idea that TTX/STX use dependence arises from
      conformational coupling of the voltage sensor domain or domains with residues in
      the toxin-binding site that are also involved in slow inactivation.

PMID- 23008438
TI  - Sex-related trends in mortality in hospitalized men and women after myocardial
      infarction between 1985 and 2008: equal benefit for women and men.
AB  - BACKGROUND: We aimed to study sex-related differences in temporal trends in short
      and long-term mortality from 1985 to 2008 in patients hospitalized for acute
      myocardial infarction. METHODS AND RESULTS: We included a total of 14 434
      consecutive patients admitted to our intensive coronary care unit between 1985
      and 2008 for myocardial infarction. A total of 4028 patients (28%) were women.
      Women were more likely to present with a higher risk profile and were equally
      likely to receive pharmacological and invasive reperfusion therapy compared with
      men. Women had a higher unadjusted mortality rate at 30 days (odds ratio, 1.3;
      95% confidence interval, 1.1-1.5) and during 20 years (hazard ratio, 1.1; 95%
      confidence interval, 1.0-1.2) of follow-up. After adjustment for baseline
      characteristics, 30-day mortality was equal (adjusted odds ratio, 1.0; 95%
      confidence interval, 0.85-1.2) but the hazard for 20-year mortality was lower
      (adjusted hazard ratio, 0.77; 95% confidence interval, 0.66-0.90) in women
      compared to men. For 30-day mortality, there was no significant interaction
      between sex and age, diagnosis, or diabetes mellitus. Survival improved between
      1985 and 2008. Temporal mortality reductions between 1985 and 2008 were at least
      as high in women as in men with myocardial infarction for both 30-day mortality
      and long-term mortality hazard. CONCLUSIONS: The fact that adjusted mortality
      rates for men and women treated for myocardial infarction in an intensive
      coronary care unit were similar and declined markedly over a 24-year period
      suggests that both sexes benefit from the evidence-based therapies that have been
      developed and implemented during this time period.

PMID- 23008439
TI  - Phosphoinositide 3-kinase gamma protects against catecholamine-induced
      ventricular arrhythmia through protein kinase A-mediated regulation of distinct
      phosphodiesterases.
AB  - BACKGROUND: Phosphoinositide 3-kinase gamma (PI3Kgamma) signaling engaged by beta
      adrenergic receptors is pivotal in the regulation of myocardial contractility and
      remodeling. However, the role of PI3Kgamma in catecholamine-induced arrhythmia is
      currently unknown. METHODS AND RESULTS: Mice lacking PI3Kgamma (PI3Kgamma(-/-))
      showed runs of premature ventricular contractions on adrenergic stimulation that
      could be rescued by a selective beta(2)-adrenergic receptor blocker and developed
      sustained ventricular tachycardia after transverse aortic constriction.
      Consistently, fluorescence resonance energy transfer probes revealed abnormal
      cAMP accumulation after beta(2)-adrenergic receptor activation in PI3Kgamma(-/-)
      cardiomyocytes that depended on the loss of the scaffold but not of the catalytic
      activity of PI3Kgamma. Downstream from beta-adrenergic receptors, PI3Kgamma was
      found to participate in multiprotein complexes linking protein kinase A to the
      activation of phosphodiesterase (PDE) 3A, PDE4A, and PDE4B but not of PDE4D.
      These PI3Kgamma-regulated PDEs lowered cAMP and limited protein kinase A-mediated
      phosphorylation of L-type calcium channel (Ca(v)1.2) and phospholamban. In
      PI3Kgamma(-/-) cardiomyocytes, Ca(v)1.2 and phospholamban were
      hyperphosphorylated, leading to increased Ca(2+) spark occurrence and amplitude
      on adrenergic stimulation. Furthermore, PI3Kgamma(-/-) cardiomyocytes showed
      spontaneous Ca(2+) release events and developed arrhythmic calcium transients.
      CONCLUSIONS: PI3Kgamma coordinates the coincident signaling of the major cardiac
      PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that prevents calcium
      dependent ventricular arrhythmia.

PMID- 23008440
TI  - Use of a novel endoscopic catheter for direct visualization and ablation in an
      ovine model of chronic myocardial infarction.
AB  - BACKGROUND: Defining the arrhythmogenic substrate is essential for successful
      ablation of scar-related ventricular tachycardia. The visual characteristics of
      endocardial ischemic scar have not been described in vivo. The goal of this study
      was (1) to quantify the visual characteristics of normal tissue, scar border
      zone, and dense scar in vivo with the use of a novel endoscopic catheter that
      allows direct endocardial visualization and (2) to correlate visual attributes of
      myocardial scar with bipolar voltage. METHODS AND RESULTS: Percutaneous transient
      balloon occlusion (150 minutes) of the mid left anterior descending coronary
      artery was performed in an ovine model. Animals survived for 41.5+/-0.7 days.
      Detailed bipolar voltage maps of the left ventricle were acquired with the use of
      NavX. Video snapshots of the endocardium were acquired at sites distributed
      throughout the left ventricle. Visual tissue characteristics of normal (>1.5 mV),
      border (0.5-1.5 mV), and dense scar (<0.5 mV) were quantified with the use of
      image processing. Radiofrequency lesions (10-20 W, 30 seconds) were delivered
      under direct visualization. Mean white-threshold pixel area was lowest in normal
      tissue (189 969+/-41 478 pixels(2)), intermediate in scar border zone (255 979+/
      36 016 pixels(2)), and highest in dense scar (324 452+/-30 152 pixels(2);
      P<0.0001 for all pairwise comparisons). Tissue whiteness, characteristic of scar,
      was inversely correlated with bipolar voltage (P<0.0001). During radiofrequency
      lesions, there was a significant increase in white-thresholded pixel area of the
      visual field after ablation (average increase, 85 381+/-52 618 pixels(2);
      P<0.001). CONCLUSIONS: Visual characteristics of chronic infarct scar in vivo
      observed with the use of a novel endoscopic catheter correlate with bipolar
      electrogram voltage. Irrigated radiofrequency lesions in normal endocardial
      tissue and postinfarction zone can be visualized and quantified with the use of
      image processing. This technology shows promise for visually based delivery of
      radiofrequency lesions for the treatment of scar-based ventricular tachycardia.

PMID- 23008441
TI  - Ca2+/calmodulin-dependent protein kinase II-based regulation of voltage-gated Na+
      channel in cardiac disease.
AB  - BACKGROUND: Human gene variants affecting ion channel biophysical activity and/or
      membrane localization are linked to potentially fatal cardiac arrhythmias.
      However, the mechanism for many human arrhythmia variants remains undefined
      despite more than a decade of investigation. Posttranslational modulation of
      membrane proteins is essential for normal cardiac function. Importantly, aberrant
      myocyte signaling has been linked to defects in cardiac ion channel
      posttranslational modifications and disease. We recently identified a novel
      pathway for posttranslational regulation of the primary cardiac voltage-gated
      Na(+) channel (Na(v)1.5) by Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII). However, a role for this pathway in cardiac disease has not been
      evaluated. METHODS AND RESULTS: We evaluated the role of CaMKII-dependent
      phosphorylation in human genetic and acquired disease. We report an unexpected
      link between a short motif in the Na(v)1.5 DI-DII loop, recently shown to be
      critical for CaMKII-dependent phosphorylation, and Na(v)1.5 function in monogenic
      arrhythmia and common heart disease. Experiments in heterologous cells and
      primary ventricular cardiomyocytes demonstrate that the human arrhythmia
      susceptibility variants (A572D and Q573E) alter CaMKII-dependent regulation of
      Na(v)1.5, resulting in abnormal channel activity and cell excitability. In silico
      analysis reveals that these variants functionally mimic the phosphorylated
      channel, resulting in increased susceptibility to arrhythmia-triggering
      afterdepolarizations. Finally, we report that this same motif is aberrantly
      regulated in a large-animal model of acquired heart disease and in failing human
      myocardium. CONCLUSIONS: We identify the mechanism for 2 human arrhythmia
      variants that affect Na(v)1.5 channel activity through direct effects on channel
      posttranslational modification. We propose that the CaMKII phosphorylation motif
      in the Na(v)1.5 DI-DII cytoplasmic loop is a critical nodal point for
      proarrhythmic changes to Na(v)1.5 in congenital and acquired cardiac disease.

PMID- 23008443
TI  - Genetic diversity and population structure of Chinese White poplar (Populus
      tomentosa) revealed by SSR markers.
AB  - An understanding of allelic diversity and population structure is important in
      developing association studies and constructing core collections for tree
      breeding. We examined population genetic differentiation in the native Populus
      tomentosa by genotyping 460 unrelated individuals using 20 species-specific
      microsatellite markers. We identified 99 alleles with a mean of 4.95 observed
      alleles per locus, indicating a moderate level of polymorphism across all
      individuals. A model-based population structure analysis divided P. tomentosa
      into 11 subpopulations (K = 11). The pattern of individual assignments into the
      subsets (K = 3) provided reasonable evidence for treating climatic zones as
      genetic regions for population genetics. The highest level of genetic variation
      was found in the southern region (i.e., N = 93, N  (P) = 11, H  (E) = 0.445, F = 
      0.102), followed by the northeastern and northwestern regions. Thus, the southern
      region is probably the center of the current species distribution. No correlation
      was found between population genetic distance and geographic distance (r =
      0.0855, P = 0.3140), indicating that geographical distance was not the principal
      factor influencing genetic differentiation in P. tomentosa. These data provide a
      starting point for conserving valuable natural resources and optimizing breeding
      programs.

PMID- 23008442
TI  - Clinical and angiographic risk stratification and differential impact on
      treatment outcomes in the Bypass Angioplasty Revascularization Investigation 2
      Diabetes (BARI 2D) trial.
AB  - BACKGROUND: The Bypass Angioplasty Revascularization Investigation 2 Diabetes
      (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt
      coronary revascularization plus intensive medical therapy versus intensive
      medical therapy alone and reported no significant difference in mortality. Among
      patients selected for coronary artery bypass graft surgery, prompt coronary
      revascularization was associated with a significant reduction in death/myocardial
      infarction/stroke compared with intensive medical therapy. We hypothesized that
      clinical and angiographic risk stratification would affect the effectiveness of
      the treatments overall and within revascularization strata. METHODS AND RESULTS:
      An angiographic risk score was developed from variables assessed at
      randomization; independent prognostic factors were myocardial jeopardy index,
      total number of coronary lesions, prior coronary revascularization, and left
      ventricular ejection fraction. The Framingham Risk Score for patients with
      coronary disease was used to summarize clinical risk. Cardiovascular event rates
      were compared by assigned treatment within high-risk and low-risk subgroups.
      Overall, no outcome differences between the intensive medical therapy and prompt
      coronary revascularization groups were seen in any risk stratum. The 5-year risk
      of death/myocardial infarction/stroke was 36.8% for intensive medical therapy
      compared with 24.8% for prompt coronary revascularization among the 381 coronary
      artery bypass graft surgery-selected patients in the highest angiographic risk
      tertile (P=0.005); this treatment effect was amplified in patients with both high
      angiographic and high Framingham risk (47.3% intensive medical therapy versus
      27.1% prompt coronary revascularization; P=0.010; hazard ratio=2.10; P=0.009).
      Treatment group differences were not significant in other clinical-angiographic
      risk groups within the coronary artery bypass graft surgery stratum, or in any
      subgroups within the percutaneous coronary intervention stratum. CONCLUSION:
      Among patients with diabetes mellitus and stable ischemic heart disease, a
      strategy of prompt coronary artery bypass graft surgery significantly reduces the
      rate of death/myocardial infarction MI/stroke in those with extensive coronary
      artery disease or impaired left ventricular function. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

PMID- 23008444
TI  - Ovarian dysgenesis in an alpaca with a minute chromosome 36.
AB  - A 4-year-old female alpaca (Lama pacos [LPA]) was presented to the Oregon State
      Veterinary Teaching Hospital for failure to display receptive behavior to males.
      Although no abnormalities were found on physical examination, transrectal
      ultrasonographic examination of the reproductive tract revealed uterine
      hypoplasia and ovarian dysgenesis. Cytogenetic analysis demonstrated a normal
      female 74,XX karyotype with 1 exceptionally small (minute) homologue of autosome
      LPA36. Chromosome analysis by Giemsa staining and DAPI- and C-banding revealed
      that the minute LPA36 was submetacentric, AT-rich, and largely heterochromatic.
      Because of the small size and lack of molecular markers, it was not possible to
      identify the origin of the minute. There is a need to improve molecular
      cytogenetic tools to further study the phenomenon of this minute chromosome and
      its relation to female reproduction in alpacas and llamas.

PMID- 23008445
TI  - Local genetic structure on breeding grounds of a long-distance migrant passerine:
      the bluethroat (Luscinia svecica) in Spain.
AB  - Breeding site fidelity can be determined by environmental features, which
      depending on their heterogeneous distribution may shape the genetic landscape of
      a population. We used 10 microsatellite loci to study the genetic variation of 83
      bluethroats (Luscinia svecica azuricollis) across 14 localities within the
      Spanish breeding population and assess the relative influence of different
      habitat characteristics (physiography and vegetation) on genetic differentiation.
      Based on the genetic variation of this population, we identified 3 geographically
      consistent genetic clusters that on average showed a higher genetic
      differentiation than among other north European populations, even those belonging
      to different subspecies. The inferred genetic clusters occurred in geographic
      areas that significantly differed in elevation. The highest genetic
      differentiation was observed between sites at different mountain ranges, as well
      as between the highest altitude sites in the northeastern locale, whereas
      vegetation type did not explain a significant percentage of genetic variation.
      The lack of correlation between geographic and genetic distances suggests that
      this pattern of genetic structure cannot be explained as a consequence of
      isolation by distance. Finally, we discuss the importance of preserving areas
      encompassing high environmental and genetic variation as a means of preserving
      evolutionary processes and adaptive potential.

PMID- 23008446
TI  - Sepsis chronically in MARS: systemic cytokine responses are always mixed
      regardless of the outcome, magnitude, or phase of sepsis.
AB  - The paradigm of systemic inflammatory response syndrome-to-compensatory anti
      inflammatory response syndrome transition implies that hyperinflammation triggers
      acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory
      cytokines) in late sepsis induces chronic deaths. However, the exact humoral
      inflammatory mechanisms attributable to sepsis outcomes remain elusive. In the
      first part of this study, we characterized the systemic dynamics of the chronic
      inflammation in dying (DIE) and surviving (SUR) mice suffering from cecal
      ligation and puncture sepsis (days 6-28). In the second part, we combined the
      current chronic and previous acute/chronic sepsis data to compare the outcome
      dependent inflammatory signatures between these two phases. A composite cytokine
      score (CCS) was calculated to compare global inflammatory responses. Mice were
      never sacrificed but were sampled daily (20 MUl) for blood. In the first part of
      the study, parameters from chronic DIE mice were clustered into the 72, 48, and
      24 h before death time points and compared with SUR of the same post-cecal
      ligation and puncture day. Cytokine increases were mixed and never preceded
      chronic deaths earlier than 48 h (3- to 180-fold increase). CCS demonstrated
      simultaneous and similar upregulation of proinflammatory and anti-inflammatory
      compartments at 24 h before chronic death (DIE 80- and 50-fold higher versus
      SUR). In the second part of the study, cytokine ratios across sepsis
      phases/outcomes indicated steady proinflammatory versus anti-inflammatory
      balance. CCS showed the inflammatory response in chronic DIE was 5-fold lower
      than acute DIE mice, but identical to acute SUR. The systemic mixed anti
      inflammatory response syndrome-like pattern (concurrent release of
      proinflammatory and anti-inflammatory cytokines) occurs irrespective of the
      sepsis phase, response magnitude, and/or outcome. Although different in
      magnitude, neither acute nor chronic septic mortality is associated with a
      predominating proinflammatory and/or anti-inflammatory signature in the blood.

PMID- 23008447
TI  - Failure to induce IFN-beta production during Staphylococcus aureus infection
      contributes to pathogenicity.
AB  - The importance of type I IFNs in the host response to viral infection is well
      established; however, their role in bacterial infection is not fully understood.
      Several bacteria (both Gram-positive and -negative) have been shown to induce IFN
      beta production in myeloid cells, but this IFN-beta is not always beneficial to
      the host. We examined whether Staphylococcus aureus induces IFN-beta from myeloid
      phagocytes, and if so, whether it is helpful or harmful to the host to do so. We
      found that S. aureus poorly induces IFN-beta production compared with other
      bacteria. S. aureus is highly resistant to degradation in the phagosome because
      it is resistant to lysozyme. Using a mutant that is more sensitive to lysozyme,
      we show that phagosomal degradation and release of intracellular ligands is
      essential for induction of IFN-beta and inflammatory chemokines downstream of IFN
      beta. Further, we found that adding exogenous IFN-beta during S. aureus infection
      (in vitro and in vivo) was protective. Together, the data demonstrate that
      failure to induce IFN-beta production during S. aureus infection contributes to
      pathogenicity.

PMID- 23008449
TI  - Development of memory CD8+ T cells and their recall responses during blood-stage
      infection with Plasmodium berghei ANKA.
AB  - Conditions required for establishing protective immune memory vary depending on
      the infecting microbe. Although the memory immune response against malaria
      infection is generally thought to be relatively slow to develop and can be lost
      rapidly, experimental evidence is insufficient. In this report, we investigated
      the generation, maintenance, and recall responses of Ag-specific memory CD8(+) T
      cells using Plasmodium berghei ANKA expressing OVA (PbA-OVA) as a model system.
      Mice were transferred with OVA-specific CD8(+) T (OT-I) cells and infected with
      PbA-OVA or control Listeria monocytogenes expressing OVA (LM-OVA). Central memory
      type OT-I cells were maintained for >2 mo postinfection and recovery from PbA
      OVA. Memory OT-I cells produced IFN-gamma as well as TNF-alpha upon activation
      and were protective against challenge with a tumor expressing OVA, indicating
      that functional memory CD8(+) T cells can be generated and maintained
      postinfection with P. berghei ANKA. Cotransfer of memory OT-I cells with naive OT
      I cells to mice followed by infection with PbA-OVA or LM-OVA revealed that clonal
      expansion of memory OT-I cells was limited during PbA-OVA infection compared with
      expansion of naive OT-I cells, whereas it was more rapid during LM-OVA infection.
      The expression of inhibitory receptors programmed cell death-1 and LAG-3 was
      higher in memory-derived OT-I cells than naive-derived OT-I cells during
      infection with PbA-OVA. These results suggest that memory CD8(+) T cells can be
      established postinfection with P. berghei ANKA, but their recall responses during
      reinfection are more profoundly inhibited than responses of naive CD8(+) T cells.

PMID- 23008448
TI  - Antigen-specific suppression of humoral immunity by anergic Ars/A1 B cells.
AB  - Autoreactive anergic B lymphocytes are considered to be dangerous because of
      their potential for activation and recruitment into autoimmune responses.
      However, they persist for days and constitute ~5% of the B cell pool. We assessed
      their functional potential in the Ars/A1 transgene model, where anergic B cells
      express a dual-reactive Ag receptor that binds, in addition to a self-Ag, the
      hapten p-azophenylarsonate (Ars). When Ars/A1 B cells were transferred into
      adoptive recipients that were immunized with foreign proteins covalently
      conjugated with Ars, endogenous IgG immune responses to both were selectively and
      severely diminished, and the development of T helper cells was impaired.
      Approximately 95% inhibition of the anti-Ars response was attained with ~4000
      transferred Ars/A1 B cells through redundant mechanisms, one of which depended on
      their expression of MHC class II but not upon secretion of IL-10 or IgM. This Ag
      specific suppressive activity implicates the autoreactive anergic B cell as an
      enforcer of immunological tolerance to self-Ags.

PMID- 23008450
TI  - COX-2 expression is upregulated by DNA hypomethylation after hematopoietic stem
      cell transplantation.
AB  - Hematopoietic stem cell transplant therapy is limited by pulmonary infections.
      Mice with fully reconstituted hematopoietic compartments, including alveolar
      macrophages (AMs), after bone marrow transplantation (BMT) have impaired host
      defense against Gram-negative Pseudomonas aeruginosa. Impaired innate immunity is
      related to increased production of PGE(2) by AMs. Cyclooxygenase (COX)-2 is the
      rate-limiting enzyme for synthesis of PGE(2) from arachidonic acid, and COX-2
      expression is elevated in AMs post-BMT. We hypothesized that epigenetic
      mechanisms may be responsible for upregulation of COX-2 in AMs. Using bisulfite
      sequencing, we observed the 5'-untranslated region and exon 1 of the COX-2 gene
      is hypomethylated in the AMs of BMT mice compared with control. COX-2 expression
      was increased in primary AMs and in the AM cell line (MHS) after treatment with 5
      aza-2'-deoxycytidine (a methyltransferase inhibitor). Methylation by SssI
      methyltransferase of a 698-bp region of the COX-2 promoter including the
      beginning of exon 1 driving a luciferase reporter silenced luciferase expression.
      Because TGF-beta1 is elevated in lungs post-BMT, we tested whether TGF-beta1
      could promote expression of COX-2 in a hypermethylated COX-2 vector, and observed
      TGF-beta1-induced modest expression of COX-2, suggesting an ability to
      demethylate the promoter. Finally, BMTs performed with marrow from mice
      expressing a dominant-negative form of the TGF-betaRII on CD11c-expressing cells
      (which includes AMs) demonstrated improved host defense and AM function. Our
      findings suggest impaired innate immunity and PGE(2) elevation post-BMT are due
      to hypomethylation of the COX-2 gene, which is at least partly regulated by TGF
      beta1.

PMID- 23008452
TI  - Medications for adolescents and young adults with autism spectrum disorders: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVE: Although many treatments have been studied in children
      with autism spectrum disorders (ASDs), less attention has focused on
      interventions that may be helpful in adolescents and young adults with ASD. The
      goal of this study was to systematically review evidence regarding medication
      treatments for individuals between the ages of 13 and 30 years with ASD. METHODS:
      The Medline, PsycINFO, and ERIC databases were searched (1980-December 2011), as
      were reference lists of included articles. Two investigators independently
      assessed studies against predetermined inclusion/exclusion criteria. Two
      investigators independently extracted data regarding participant and intervention
      characteristics, assessment techniques, and outcomes and assigned overall quality
      and strength of evidence ratings on the basis of predetermined criteria. RESULTS:
      Eight studies of medications were identified that focused on 13- to 30-year-olds
      with ASD; 4 of the studies were of fair quality. The strength of evidence was
      insufficient for all outcomes associated with medications tested in this
      population; however, the 2 available studies of the atypical antipsychotic
      medication risperidone in this age range were consistent with the moderate
      evidence in children with ASD for treating problem behavior, including
      aggression, and high strength of evidence for adverse events, including sedation
      and weight gain. CONCLUSIONS: There is a marked lack of data on use of medication
      treatments for adolescents and young adults with ASD. The evidence on the use of
      risperidone in this age range is insufficient when considered alone but is
      consistent with the data in the population of children with ASD.

PMID- 23008451
TI  - Cross-immunoreactivity between bacterial aquaporin-Z and human aquaporin-4:
      potential relevance to neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is a chronic inflammatory disease of the CNS that is
      mediated, in part, by a self-reactive Ab against the astrocyte aquaporin-4
      protein. In the current study, we examined the possibility and the biological
      significance of cross-immunoreactivity between bacterial aquaporin-Z and human
      aquaporin-4 proteins. Sequence-alignment analysis of these proteins revealed
      several regions of significant structural homology. Some of the homologous
      regions were also found to overlap with important immune and disease-relevant
      epitopes. Cross-immunoreactivity between aquaporin-Z and aquaporin-4 was
      investigated and ascertained in multiple immune-based assays using sera from
      patients with neuromyelitis optica, immune mouse serum, and Abs raised against
      aquaporin-Z. The biological significance of this phenomenon was established in
      series of experiments demonstrating that induction of an immune response against
      aquaporin-Z or its homologous regions can also trigger an autoimmune reaction
      against aquaporin-4 and inflammation of the CNS. Our study indicates that the
      autoimmune response against aquaporin-4 in neuromyelitis optica may be triggered
      by infection-induced cross-immunoreactivity and presents a new perspective on the
      pathogenesis of this disease.

PMID- 23008453
TI  - Increased expression of the glucocorticoid receptor beta in infants with RSV
      bronchiolitis.
AB  - OBJECTIVES: The majority of studies on glucocorticoid treatment in respiratory
      syncytial virus (RSV) bronchiolitis concluded that there are no beneficial
      effects. We hypothesized that RSV-infected patients may have an increased
      glucocorticoid receptor (GR) beta expression, the isoform that is unable to bind
      cortisol and exert an antiinflammatory action. METHODS: By using real-time
      polymerase chain reaction, we studied the expression of alpha and beta GR in the
      peripheral blood mononuclear cells obtained from 49 RSV-infected infants (<1 year
      of age) with severe (n = 29) and mild to moderate (n = 20) illness. In plasma, we
      analyzed the level of cortisol by radioimmunoassay and inflammatory cytokines
      interleukin (IL)-10, IL-6, tumor necrosis factor-alpha, IL-1beta, IL-8, IL-12p70,
      IL-2, IL-4, IL-5, interferon-gamma, and IL-17 by cytometric beads assay.
      Statistical analysis was performed by nonparametric analysis of variance.
      RESULTS: We found a significant increase of beta GR expression in patients with
      severe illness compared with those with mild disease (P < .001) and with a group
      of healthy controls (P < .01). The alpha:beta GR ratio decreased significantly in
      infants with severe disease compared with those with mild illness (P < .01) and
      with normal controls (P < .001). The expression of beta GR was positively
      correlated with the clinical score of severity (r = .54; P < .0001). CONCLUSIONS:
      The decrease of the alpha:beta GR ratio by an increase of beta receptors
      expression is related to illness severity and may partly explain the
      insensitivity to corticoid treatment in RSV-infected infants. The increased
      expression of beta GR could be a marker of disease severity.

PMID- 23008455
TI  - Trampoline safety in childhood and adolescence.
AB  - Despite previous recommendations from the American Academy of Pediatrics
      discouraging home use of trampolines, recreational use of trampolines in the home
      setting continues to be a popular activity among children and adolescents. This
      policy statement is an update to previous statements, reflecting the current
      literature on prevalence, patterns, and mechanisms of trampoline-related
      injuries. Most trampoline injuries occur with multiple simultaneous users on the
      mat. Cervical spine injuries often occur with falls off the trampoline or with
      attempts at somersaults or flips. Studies on the efficacy of trampoline safety
      measures are reviewed, and although there is a paucity of data, current
      implementation of safety measures have not appeared to mitigate risk
      substantially. Therefore, the home use of trampolines is strongly discouraged.
      The role of trampoline as a competitive sport and in structured training settings
      is reviewed, and recommendations for enhancing safety in these environments are
      made.

PMID- 23008454
TI  - Antibiotic exposure and IBD development among children: a population-based cohort
      study.
AB  - OBJECTIVE: To determine whether childhood antianaerobic antibiotic exposure is
      associated with the development of inflammatory bowel disease (IBD). METHODS:
      This retrospective cohort study employed data from 464 UK ambulatory practices
      participating in The Health Improvement Network. All children with >= 2 years of
      follow-up from 1994 to 2009 were followed between practice enrollment and IBD
      development, practice deregistration, 19 years of age, or death; those with
      previous IBD were excluded. All antibiotic prescriptions were captured.
      Antianaerobic antibiotic agents were defined as penicillin, amoxicillin,
      ampicillin, penicillin/beta-lactamase inhibitor combinations, tetracyclines,
      clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin. RESULTS:
      A total of 1072426 subjects contributed 6.6 million person-years of follow-up;
      748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed
      and exposed subjects were 0.83 and 1.52/10000 person-years, respectively, for an
      84% relative risk increase. Exposure throughout childhood was associated with
      developing IBD, but this relationship decreased with increasing age at exposure.
      Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95%
      confidence interval [CI]: 1.66-18.28) but decreased to 2.62 (95% CI: 1.61-4.25)
      and 1.57 (95% CI: 1.35-1.84) by 5 and 15 years, respectively. Each antibiotic
      course increased the IBD hazard by 6% (4%-8%). A dose-response effect existed,
      with receipt of >2 antibiotic courses more highly associated with IBD development
      than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13
      10.68) versus 3.33 (95% CI: 1.69-6.58). CONCLUSIONS: Childhood antianaerobic
      antibiotic exposure is associated with IBD development.

PMID- 23008456
TI  - Unfilled prescriptions in pediatric primary care.
AB  - BACKGROUND AND OBJECTIVES: Filling a prescription is the important first step in
      medication adherence, but has not been studied in pediatric primary care. The
      objective of this study was to use claims data to determine the rate of unfilled
      prescriptions in pediatric primary care and examine factors associated with
      prescription filling. METHODS: This retrospective observational study of
      pediatric primary care patients compares prescription data from an electronic
      medical record with insurance claims data. Illinois Medicaid provided claims data
      for 4833 patients who received 16953 prescriptions during visits at 2 primary
      care sites over 26 months. Prescriptions were compared with claims to determine
      filling within 1 day and 60 days. Clinical and demographic variables significant
      in univariate analysis were included in logistic regression models. RESULTS:
      Patients were 51% male; most (84%) spoke English and were African American
      (38.7%) or Hispanic (39.1%). Seventy-eight percent of all prescriptions were
      filled. Among filled prescriptions, 69% were filled within 1 day. African
      American, Hispanic, and male patients were significantly more likely to have
      filled prescriptions. Younger age was associated with filling within 1 day but
      not with filling within 60 days. Prescriptions for antibiotics, from one of the
      clinic sites, from sick/follow-up visits, and electronic prescriptions were
      significantly more likely to be filled. CONCLUSIONS: More than 20% of
      prescriptions in a pediatric primary care setting were never filled. The
      significant associations with clinical site, visit type, and electronic
      prescribing suggest system-level factors that affect prescription filling.
      Development of interventions to increase adherence should account for the factors
      that affect primary adherence.

PMID- 23008457
TI  - The pediatrician's role in supporting adoptive families.
AB  - Each year, more children join families through adoption. Pediatricians have an
      important role in assisting adoptive families in the various challenges they may
      face with respect to adoption. The acceptance of the differences between families
      formed through birth and those formed through adoption is essential in promoting
      positive emotional growth within the family. It is important for pediatricians to
      be aware of the adoptive parents' need to be supported in their communication
      with their adopted children.

PMID- 23008459
TI  - Severe poisoning after accidental pediatric ingestion of glycol ethers.
AB  - Human glycol ether poisonings are sparsely reported in the medical literature. We
      describe a healthy 22-month-old boy who accidentally drank up to 330 mL of brake
      fluid containing a 75% bleed of various glycol ethers (5%-50% polyethylene glycol
      monomethyl ether, 15%-40% triethylene glycol monoethyl ether, 1%-30% triethylene
      glycol monomethyl ether, 1%-25% triethylene glycol monobutyl ether, 1%-20%
      polyethylene glycol, monobutyl ether, 1%-20% triethylene glycol, and <10% of
      other glycol ethers). Within 4 hours, he became somnolent and developed a
      persistent metabolic acidosis. Thirty minutes later, he received 1 dose of
      fomepizole. Neither progression nor improvement in clinical or metabolic status
      was noted after the fomepizole. He received hemodialysis for 3 hours ~8 hours
      after ingestion, and his symptoms resolved resulting in an uneventfully recovery.

PMID- 23008460
TI  - Vitamin D status of exclusively breastfed 4-month-old infants supplemented during
      different seasons.
AB  - OBJECTIVE: To examine the vitamin D status of 4-month-old exclusively breastfed
      infants supplemented with 400 IU daily of vitamin D and to determine whether
      there was any seasonal variation in serum 25-hydroxyvitamin D (25(OH)D) levels of
      infants. METHODS: In this cross-sectional study, serum calcium, phosphorus,
      alkaline phosphatase, parathyroid hormone, and 25(OH)D levels of 143 exclusively
      breastfed 4-month-old infants supplemented daily with 400 IU of vitamin D were
      measured in a temperate latitude, Izmir, Turkey, between May 2008 and April 2009.
      A questionnaire on demographic characteristics of infants and mothers, vitamin D
      supplementation of infants after birth, mothers' multivitamin supplementation,
      dressing habits, and consumption of dairy products during pregnancy was used.
      RESULTS: Vitamin D deficiency (<= 50 nmol/L) and insufficiency (51-74 nmol/L)
      were determined in 40 (28%) and 55 (38.5%) infants, respectively. During winter
      days, serum 25(OH)D levels were <20 ng/mL in 45.4% of infants and <10 ng/mL in
      10.6% of infants. Season of blood sampling, compliance of vitamin D
      supplementation, maternal education level, and consumption of dairy products were
      highly predictive of serum 25(OH)D levels in multiple linear regression analysis
      (P < .05). The use of the Pearson correlation test found a statistically
      significant negative correlation between 25(OH)D and parathyroid hormone levels
      (r = -0.419, P < .001). CONCLUSIONS: Despite supplementation with 400 IU of
      vitamin D daily, the rate of vitamin D deficiency was worryingly high in 4-month
      old exclusively breastfed infants living in Izmir, Turkey. So, additional studies
      are needed to clarify optimal amount of vitamin D supplementation to the infants,
      especially during winter days.

PMID- 23008461
TI  - Amitriptyline cream ingestion in a 1-year-old boy.
AB  - A 1-year-old boy presented to the emergency department with drowsiness after
      intoxication from amitriptyline cream. The amitriptyline level in his blood was
      in the high-therapeutic range for adults. He was admitted for cardiac monitoring.
      Except for a short episode with irregular heart rate, he recovered completely
      within 24 hours without adjuvant treatment. Amitriptyline is known as an
      antidepressant but is also prescribed for neuropathic pain. It is usually
      prescribed in tablet form; the cream is a novel application. In children,
      intoxication with amitriptyline may cause drowsiness, seizures, coma,
      hypotension, tachycardia, and life-threatening cardiac arrhythmias. This is the
      first case report presenting intoxication in a child with amitriptyline cream. It
      stresses the importance of keeping children away from the medicine cabinet, even
      from creams or ointments.

PMID- 23008462
TI  - Assessment and management of inguinal hernia in infants.
AB  - Inguinal hernia repair in infants is a routine surgical procedure. However,
      numerous issues, including timing of the repair, the need to explore the
      contralateral groin, use of laparoscopy, and anesthetic approach, remain
      unsettled. Given the lack of compelling data, consideration should be given to
      large, prospective, randomized controlled trials to determine best practices for
      the management of inguinal hernias in infants.

PMID- 23008464
TI  - Evaluation of interobserver agreement of apgar scoring in preterm infants.
AB  - BACKGROUND AND OBJECTIVES: Apgar scoring is accepted by medical professionals
      both as a measure of the infant's clinical status and the infant's response to
      resuscitation. Recent studies, however, have suggested significant variability
      when used for scoring preterm infants. We hypothesized that agreement in Apgar
      scoring would improve with increasing gestational age and at low levels of
      respiratory support. We also hypothesized that grimace and muscle tone would
      demonstrate the least agreement. METHODS: Neonatologists from the Perinatal
      Section of the American Academy of Pediatrics were presented with 4 film clip
      cases via a secure online survey: (1) full-term infant in room air; (2) 28 weeks'
      gestation infant with continuous positive airway pressure; (3) 28 weeks'
      gestation infant intubated; and (4) 24 weeks' gestation infant intubated.
      Participants were shown 30-second clips at 1, 5, and 10 minutes of life and were
      asked to provide Apgar scores. kappa coefficients were used to compare agreement
      for each component. RESULTS: A total of 335 neonatologists participated in the
      survey. kappa coefficients in the full-term infant for respiratory effort (0.94,
      0.91), grimace (0.91, 0.90), and muscle tone (0.91, 0.89) demonstrated almost
      perfect agreement at 1 and 5 minutes. For preterm infants, respiratory effort
      (range: 0.07-0.40), muscle tone (range: 0.10-0.75), and grimace (range: 0.11
      0.71) all demonstrated disagreement at 1, 5, and 10 minutes of life unless the
      infants were apneic and limp. CONCLUSIONS: An improved delivery room score that
      decreases variability among medical care professionals is needed to accurately
      reflect the clinical status of preterm infants.

PMID- 23008465
TI  - Erythropoietin for neuroprotection in neonatal encephalopathy: safety and
      pharmacokinetics.
AB  - OBJECTIVE: To determine the safety and pharmacokinetics of erythropoietin (Epo)
      given in conjunction with hypothermia for hypoxic-ischemic encephalopathy (HIE).
      We hypothesized that high dose Epo would produce plasma concentrations that are
      neuroprotective in animal studies (ie, maximum concentration = 6000-10000 U/L;
      area under the curve = 117000-140000 U*h/L). METHODS: In this multicenter, open
      label, dose-escalation, phase I study, we enrolled 24 newborns undergoing
      hypothermia for HIE. All patients had decreased consciousness and acidosis (pH <
      7.00 or base deficit >= 12), 10-minute Apgar score <= 5, or ongoing resuscitation
      at 10 minutes. Patients received 1 of 4 Epo doses intravenously: 250 (N = 3), 500
      (N = 6), 1000 (N = 7), or 2500 U/kg per dose (N = 8). We gave up to 6 doses every
      48 hours starting at <24 hours of age and performed pharmacokinetic and safety
      analyses. RESULTS: Patients received mean 4.8 +/- 1.2 Epo doses. Although Epo
      followed nonlinear pharmacokinetics, excessive accumulation did not occur during
      multiple dosing. At 500, 1000, and 2500 U/kg Epo, half-life was 7.2, 15.0, and
      18.7 hours; maximum concentration was 7046, 13780, and 33316 U/L, and total Epo
      exposure (area under the curve) was 50306, 131054, and 328002 U*h/L,
      respectively. Drug clearance at a given dose was slower than reported in uncooled
      preterm infants. No deaths or serious adverse effects were seen. CONCLUSIONS: Epo
      1000 U/kg per dose intravenously given in conjunction with hypothermia is well
      tolerated and produces plasma concentrations that are neuroprotective in animals.
      A large efficacy trial is needed to determine whether Epo add-on therapy further
      improves outcome in infants undergoing hypothermia for HIE.

PMID- 23008466
TI  - An amino acid substitution inhibits specialist herbivore production of an
      antagonist effector and recovers insect-induced plant defenses.
AB  - Plants respond to insect herbivory through the production of biochemicals that
      function as either direct defenses or indirect defenses via the attraction of
      natural enemies. While attack by closely related insect pests can result in
      distinctive levels of induced plant defenses, precise biochemical mechanisms
      responsible for differing responses remain largely unknown. Cowpea (Vigna
      unguiculata) responds to Fall armyworm (Spodoptera frugiperda) herbivory through
      the detection of fragments of chloroplastic ATP synthase gamma-subunit proteins,
      termed inceptin-related peptides, present in larval oral secretions (OS). In
      contrast to generalists like Fall armyworm, OS of the legume-specializing
      velvetbean caterpillar (VBC; Anticarsia gemmatalis) do not elicit ethylene
      production and demonstrate significantly lower induced volatile emission in
      direct herbivory comparisons. Unlike all other Lepidoptera OS examined, which
      preferentially contain inceptin (Vu-In; +ICDINGVCVDA-), VBC OS contain
      predominantly a C-terminal truncated peptide, Vu-In(-A) (+ICDINGVCVD-). Vu-In(-A)
      is both inactive and functions as a potent naturally occurring antagonist of Vu
      In-induced responses. To block antagonist production, amino acid substitutions at
      the C terminus were screened for differences in VBC gut proteolysis. A valine
      substituted peptide (Vu-In(DeltaV); +ICDINGVCVDV-) retaining full elicitor
      activity was found to accumulate in VBC OS. Compared with the native polypeptide,
      VBC that previously ingested 500 pmol of the valine-modified chloroplastic ATP
      synthase gamma-subunit precursor elicited significantly stronger plant responses
      in herbivory assays. We demonstrate that a specialist herbivore minimizes the
      activation of defenses by converting an elicitor into an antagonist effector and
      identify an amino acid substitution that recovers these induced plant defenses to
      a level observed with generalist herbivores.

PMID- 23008467
TI  - Cerebral embolization during transcatheter aortic valve implantation.

PMID- 23008468
TI  - Childhood exposures to ozone: the fast track to cardiovascular disease?

PMID- 23008469
TI  - Bridging evidence-based practice and practice-based evidence in periprocedural
      anticoagulation.

PMID- 23008470
TI  - Evolution of hypertrophic cardiomyopathy to a contemporary treatable disease.

PMID- 23008472
TI  - Optical coherence tomography findings in Tako-Tsubo cardiomyopathy.

PMID- 23008473
TI  - Coronary air embolism and cardiogenic shock during computed tomography-guided
      needle biopsy of the lung.

PMID- 23008471
TI  - Guided antithrombotic therapy: current status and future research direction:
      report on a National Heart, Lung and Blood Institute working group.

PMID- 23008475
TI  - Letter by Csont and Ferdinandy regarding article, "ischemic conditioning protects
      the uremic heart in a rodent model of myocardial infarction".

PMID- 23008476
TI  - Prostate cancer mortality following active surveillance versus immediate radical
      prostatectomy.
AB  - PURPOSE: [corrected] Active surveillance has been endorsed for low-risk prostate
      cancer, but information about long-term outcomes and comparative effectiveness of
      active surveillance is lacking. The purpose of this study is to project prostate
      cancer mortality under active surveillance followed by radical prostatectomy
      versus under immediate radical prostatectomy. EXPERIMENTAL DESIGN: A simulation
      model was developed to combine information on time from diagnosis to treatment
      under active surveillance and associated disease progression from a Johns Hopkins
      active surveillance cohort (n = 769), time from radical prostatectomy to
      recurrence from cases in the CaPSURE database with T-stage <= T2a (n = 3,470),
      and time from recurrence to prostate cancer death from a T-stage <= T2a Johns
      Hopkins cohort of patients whose disease recurred after radical prostatectomy (n
      = 963). Results were projected for a hypothetical cohort aged 40 to 90 years with
      low-risk prostate cancer (T-stage <= T2a, Gleason score <= 6, and prostate
      specific antigen level <= 10 ng/mL). RESULTS: The model projected that 2.8% of
      men on active surveillance and 1.6% of men with immediate radical prostatectomy
      would die of their disease in 20 years. Corresponding lifetime estimates were
      3.4% for active surveillance and 2.0% for immediate radical prostatectomy. The
      average projected increase in life expectancy associated with immediate radical
      prostatectomy was 1.8 months. On average, the model projected that men on active
      surveillance would remain free of treatment for an additional 6.4 years relative
      to men treated immediately. CONCLUSIONS: Active surveillance is likely to produce
      a very modest decline in prostate cancer-specific survival among men diagnosed
      with low-risk prostate cancer but could lead to significant benefits in terms of
      quality of life.

PMID- 23008485
TI  - A joint effort to fight arthritis.

PMID- 23008484
TI  - Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across
      endothelial cells.
AB  - Lipoprotein lipase (LPL) is secreted into the interstitial spaces by adipocytes
      and myocytes but then must be transported to the capillary lumen by GPIHBP1, a
      glycosylphosphatidylinositol-anchored protein of capillary endothelial cells. The
      mechanism by which GPIHBP1 and LPL move across endothelial cells remains unclear.
      We asked whether the transport of GPIHBP1 and LPL across endothelial cells was
      uni- or bidirectional. We also asked whether GPIHBP1 and LPL are transported
      across cells in vesicles and whether this transport process requires caveolin-1.
      The movement of GPIHBP1 and LPL across cultured endothelial cells was
      bidirectional. Also, GPIHBP1 moved bidirectionally across capillary endothelial
      cells in live mice. The transport of LPL across endothelial cells was inhibited
      by dynasore and genistein, consistent with a vesicular transport process. Also,
      transmission electron microscopy (EM) and dual-axis EM tomography revealed
      GPIHBP1 and LPL in invaginations of the plasma membrane and in vesicles. The
      movement of GPIHBP1 across capillary endothelial cells was efficient in the
      absence of caveolin-1, and there was no defect in the internalization of LPL by
      caveolin-1-deficient endothelial cells in culture. Our studies show that GPIHBP1
      and LPL move bidirectionally across endothelial cells in vesicles and that
      transport is efficient even when caveolin-1 is absent.

PMID- 23008486
TI  - Body fat as metaphor: from harmful to helpful.

PMID- 23008487
TI  - Five things to know about...carpometacarpal osteoarthritis of the thumb.

PMID- 23008488
TI  - Real-time access to prescription drug monitoring databases.

PMID- 23008489
TI  - Pregnancy complications among women born preterm.
AB  - BACKGROUND: Adults who were born with low birth weights are at increased risk of
      cardiovascular and metabolic conditions, including pregnancy complications. Low
      birth weight can result from intrauterine growth restriction, preterm birth or
      both. We examined the relation between preterm birth and pregnancy complications
      later in life. METHODS: We conducted a population-based cohort study in the
      province of Quebec involving 7405 women born preterm (554 < 32 weeks, 6851 at 32
      36 weeks) and a matched cohort of 16 714 born at term between 1976 and 1995 who
      had a live birth or stillbirth between 1987 and 2008. The primary outcome
      measures were pregnancy complications (gestational diabetes, gestational
      hypertension, and preeclampsia or eclampsia). RESULTS: Overall, 19.9% of women
      born at less than 32 weeks, 13.2% born at 32-36 weeks and 11.7% born at term had
      at least 1 pregnancy complication at least once during the study period (p <
      0.001). Women born small for gestational age (both term and preterm) had
      increased odds of having at least 1 pregnancy complication compared with women
      born at term and at appropriate weight for gestational age. After adjustment for
      various factors, including birth weight for gestational age, the odds of
      pregnancy complications associated with preterm birth was elevated by 1.95-fold
      (95% confidence interval [CI] 1.54-2.47) among women born before 32 weeks'
      gestation and 1.14-fold (95% CI 1.03-1.25) among those born at 32-36 weeks'
      gestation relative to women born at term. INTERPRETATION: Being born preterm, in
      addition to, and independent of, being small for gestational age, was associated
      with a significantly increased risk of later having pregnancy complications.

PMID- 23008490
TI  - The Koebner phenomenon: psoriasis in tattoos.

PMID- 23008491
TI  - What does the feminization of family medicine mean?

PMID- 23008492
TI  - Promoting pride in practice.

PMID- 23008494
TI  - Systematic approach to CPR training urged.

PMID- 23008495
TI  - Helsinki doctrine under review.

PMID- 23008496
TI  - Personalized-medicine trials on the rise.

PMID- 23008497
TI  - Uncertainty Over DAT Testing.

PMID- 23008498
TI  - Studies support risk-based mammography screening.

PMID- 23008501
TI  - Preclinical characterization of a novel class of 18F-labeled PET tracers for
      amyloid-beta.
AB  - Imaging of amyloid-beta (Abeta) plaques by PET is more and more integrated into
      concepts for Alzheimer disease (AD) diagnosis and drug development. The objective
      of this study was to find novel chemical entities that can be transformed into
      (18)F-labeled Abeta tracers with favorable brain washout kinetics and low
      background signal. METHODS: High-throughput screening of a large chemical library
      was used to identify new ligands for fibrillar aggregates of Abeta(1-42) peptide.
      Thirty-two fluorinated derivatives were synthesized and tested for their affinity
      toward AD brain homogenate. Twelve ligands have been radiolabeled with (18)F. The
      pharmacokinetic properties of the radioligands were investigated in mouse and
      monkey biodistribution studies. Binding characteristics were determined by
      autoradiography of AD brain sections in vitro and using amyloid precursor protein
      transgenic mice in vivo. RESULTS: The systematic search for Abeta imaging agents
      revealed several fluorinated derivatives with nanomolar affinity for Abeta. The
      fluoropyridyl derivative BAY 1008472 showed a high initial brain uptake (6.45
      percentage injected dose per gram at 2 min) and rapid brain washout (ratio of
      percentage of injected dose per gram of tissue at 2 and 30 min after injection,
      9.2) in mice. PET studies of healthy rhesus monkeys confirmed the high initial
      brain uptake of BAY 1008472 (2.52 standardized uptake value at peak) and a fast
      elimination of total radioactivity from gray and white matter areas (ratio of
      standardized uptake value at peak uptake and 60 min 11.0). In autoradiographic
      analysis, BAY 1008472 selectively detected Abeta deposits in human AD brain
      sections with high contrast and did not bind to tau- or alpha-synuclein
      pathologies. Finally, ex vivo autoradiography of brain sections from amyloid
      precursor protein-transgenic mice confirmed that BAY 1008472 is indeed suitable
      for the in vivo detection of Abeta plaques. CONCLUSION: A new chemical class of
      Abeta tracers has been identified by high-throughput screening. The fluoropyridyl
      derivative BAY 1008472 shows a favorable preclinical profile including low
      background binding in gray and white matter. These properties might qualify this
      new tracer, in particular, to detect subtle amounts or changes of Abeta burden in
      presymptomatic AD and during therapy.

PMID- 23008502
TI  - Early life trauma exposure and stress sensitivity in young children.
AB  - OBJECTIVE: The current study replicates and extends work with adults that
      highlights the relationship between trauma exposure and distress in response to
      subsequent, nontraumatic life stressors. METHODS: The sample included 213 2-4
      year-old children in which 64.3% had a history of potential trauma exposure.
      Children were categorized into 4 groups based on trauma history and current life
      stress. RESULTS: In a multivariate analysis of variance, trauma-exposed children
      with current life stressors had elevated internalizing and externalizing problems
      compared with trauma-exposed children without current stress and nontrauma
      exposed children with and without current stressors. The trauma-exposed groups
      with or without current stressors did not differ on posttraumatic stress disorder
      symptom severity. Accounting for number of traumatic events did not change these
      results. CONCLUSIONS: These findings suggest that early life trauma exposure may
      sensitize young children and place them at risk for internalizing or
      externalizing problems when exposed to subsequent, nontraumatic life stressors.

PMID- 23008503
TI  - Cyclooxygenase (COX)-1 and COX-2 both play an important role in the protection of
      the duodenal mucosa in cats.
AB  - Although nonsteroidal anti-inflammatory drugs often cause ulcers in the duodenum
      in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of
      duodenal ulcers has not been fully elucidated. We examined in cats the 1)
      ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib,
      meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and
      cimetidine on the expression of COX isoforms and prostaglandin E(2) (PGE(2))
      level in the duodenum, and 3) localization of COX isoforms in the duodenum. COX
      inhibitors were administered after the morning meal in cats once daily for 3
      days. Gastrointestinal lesions were examined on day 4. Localization and
      expression of COX isoforms (by immunohistochemistry, Western blot) and PGE(2)
      level (by enzyme immunoassay) were examined. Results were as follows. First,
      selective COX-1 or COX-2 inhibitors alone produced marked ulcers in the duodenum
      but did not cause obvious lesions in the small intestine. Coadministration of SC
      560 and celecoxib produced marked lesions in the small intestine. Second, feeding
      increased both the expression of COX isoforms and PGE(2) level in the duodenum,
      and the effects were markedly inhibited by pretreatment with cimetidine. Third,
      COX-1 was localized in goblet and Brunner's gland cells, Meissner's and
      Auerbach's plexus, smooth muscle cells, and arterioles; and COX-2 was observed in
      capillaries, venules, and basal granulated cells. The expression of COX isoforms
      in the duodenum is up-regulated by feeding, and inhibition of either COX-1 or COX
      2 causes ulcers in the duodenum, suggesting that both isoforms play an important
      role in the protection of the duodenal mucosa.

PMID- 23008504
TI  - Endothelial nitric oxide synthase-independent release of nitric oxide in the
      aorta of the spontaneously hypertensive rat.
AB  - In the aorta of male spontaneously hypertensive rats (SHR), but not in that of
      normotensive Wistar-Kyoto rats (WKY), contractions to phenylephrine obtained in
      the presence of L-NAME [inhibitor of nitric oxide synthase (NOS)] and
      indomethacin (inhibitor of cyclooxygenase) are inhibited by an unknown
      endothelium-derived factor. The present study aimed to identify the mechanism
      underlying this endothelium-dependent inhibition in the SHR aorta. Aortic rings
      of male SHR and WKY, with and without endothelium, were suspended in organ
      chambers in the presence of indomethacin and L-NAME for the measurement of
      isometric tension. Contractions to phenylephrine were smaller in SHR aortae with
      endothelium than in those without, but were similar in the two types of
      preparations of WKY aortae. The endothelium-dependent, NOS-independent inhibition
      of phenylephrine-induced contraction was abolished by oxyhemoglobin
      [extracellular NO scavenger], carboxy-PTIO (NO scavenger) and ODQ (inhibitor of
      soluble guanylyl cyclase). It was unmasked not only by indomethacin but also by
      apocynin (antioxidant), but inhibited by diphenyleneiodonium (inhibitor of
      flavoproteins including cytochrome P450 reductase). The cytochrome P450 reductase
      protein expression was similar in SHR and WKY aortae. However, the level of
      nitrate and nitrite, substrates of cytochrome P450 reductase, were higher in SHR
      than WKY plasma and aortae. Therefore, in SHR but not WKY aortae, eNOS
      independent NO is formed by cytochrome P450 reductase.

PMID- 23008505
TI  - Prognostic implication of Doppler echocardiographic derived coronary flow reserve
      in patients with left bundle branch block.
AB  - AIMS: Myocardial ischaemia during pharmacological stress echocardiography is a
      strong prognostic predictor in patients with a left bundle branch block (LBBB).
      However, the additive value of Doppler-derived coronary flow reserve (CFR) during
      pharmacological stress testing remains to be investigated in this subset of
      patients. METHODS AND RESULTS: The study group consisted of 324 LBBB patients
      (187 men; age 68 +/- 10 years) with known (n = 74) or suspected (n = 250)
      coronary artery disease who had undergone dipyridamole (up to 0.84 mg/kg over 6')
      stress echocardiography with CFR assessment of left anterior descending (LAD) by
      Doppler. A value of CFR <= 2.0 was considered abnormal. The median duration of
      follow-up was 15 months (first to third quartile: 8-34 months). Of the 324
      patients, 52 (16%) had ischaemia at stress echo by wall motion criteria, and 139
      (43%) had a CFR <= 2. During follow-up, 51 (16%) events occurred: 37 deaths and
      14 myocardial infarctions (MIs). Age (HR: 1.09, 95% CI: 1.04-1.15, P < 0.0001),
      resting wall motion score index (HR: 5.29, 95% CI: 2.36-11.89, P < 0.0001),
      smoking habit (HR: 4.38, 95% CI: 1.93-9.91, P < 0.0001), and CFR <= 2 (4.69, 95%
      CI: 1.96-11.19, P = 0.001) were independently correlated with mortality, while
      CFR <= 2 (HR: 3.91, 95% CI: 1.90-8.04, P < 0.0001), age (HR: 1.06, 95% CI: 1.02
      1.10, P = 0.001), smoking habit (HR: 2.25, 95% CI: 1.18-4.30, P = 0.01),
      ischaemia at stress echo (HR: 2.30, 95% CI: 1.11-4.77, P = 0.02), and resting
      wall motion score index (HR: 2.17, 95% CI: 1.11-4.25, P = 0.02) were
      independently correlated with death or MI. Four-year mortality and 4-year hard
      event rate were markedly higher in patients with CFR <= 2 than in those with CFR
      >2 (49 vs. 6% and 56 vs. 8%, respectively; P < 0.0001 for both). A CFR of <= 2
      was associated with a significantly higher annual hard event rate independently
      of age, sex, ejection fraction, history of coronary artery disease, diabetes, and
      hypertension. Moreover, it was correlated with an increased (P < 0.0001) yearly
      mortality and event rate in patients with non-ischaemic stress echo conducted on
      therapy. At incremental analysis, a CFR of <= 2 added prognostic value to
      clinical findings, resting wall motion score index, ongoing anti-ischaemic
      therapy, and ischaemia at stress echo when both death and death or MI were the
      clinical endpoints. CONCLUSIONS: Abnormal CFR on LAD is a strong and independent
      indicator of mortality and death or MI in patients with LBBB, and is associated
      with markedly increased risk also in the subset of patients with stress echo
      negative for ischaemia on therapy.

PMID- 23008506
TI  - Deletion of the ageing gene p66(Shc) reduces early stroke size following
      ischaemia/reperfusion brain injury.
AB  - AIMS: Stroke is a leading cause of morbidity and mortality, and its incidence
      increases with age. Both in animals and in humans, oxidative stress appears to
      play an important role in ischaemic stroke, with or without reperfusion. The
      adaptor protein p66(Shc) is a key regulator of reactive oxygen species (ROS)
      production and a mediator of ischaemia/reperfusion damage in ex vivo hearts.
      Hence, we hypothesized that p66(Shc) may be involved in ischaemia/reperfusion
      brain damage. To this end, we investigated whether genetic deletion of p66(Shc)
      protects from ischaemia/reperfusion brain injury. METHODS AND RESULTS: Transient
      middle cerebral artery occlusion (MCAO) was performed to induce
      ischaemia/reperfusion brain injury in wild-type (Wt) and p66(Shc) knockout mice
      (p66(Shc-/-)), followed by 24 h of reperfusion. Cerebral blood flow and blood
      pressure measurements revealed comparable haemodynamics in both experimental
      groups. Neuronal nuclear antigen immunohistochemical staining showed a
      significantly reduced stroke size in p66(Shc-/-) when compared with Wt mice (P <
      0.05, n = 7-8). In line with this, p66(Shc-/-) mice exhibited a less impaired
      neurological function and a decreased production of free radicals locally and
      systemically (P < 0.05, n = 4-5). Following MCAO, protein levels of gp91phox
      nicotinamide adenine dinucleotide phosphate oxidase subunit were increased in
      brain homogenates of Wt (P < 0.05, n = 4), but not of p66(Shc-/-) mice. Further,
      reperfusion injury in Wt mice induced p66(Shc) protein in the basilar and middle
      cerebral artery, but not in brain tissue, suggesting a predominant involvement of
      vascular p66(Shc). CONCLUSION: In the present study, we show that the deletion of
      the ageing gene p66(Shc) protects mice from ischaemia/reperfusion brain injury
      through a blunted production of free radicals. The ROS mediator p66(Shc) may
      represent a novel therapeutical target for the treatment of ischaemic stroke.

PMID- 23008507
TI  - Safety of provocative tests of coronary artery spasm and prediction of long-term
      outcome: need for an innovative clinical research strategy.

PMID- 23008508
TI  - Predictors of functional decline in elderly patients undergoing transcatheter
      aortic valve implantation (TAVI).
AB  - Aims This study aimed to assess functional course in elderly patients undergoing
      transcatheter aortic valve implantation (TAVI) and to find predictors of
      functional decline. Methods and results In this prospective cohort, functional
      course was assessed in patients >=70 years using basic activities of daily living
      (BADL) before and 6 months after TAVI. Baseline EuroSCORE, STS score, and a
      frailty index (based on assessment of cognition, mobility, nutrition,
      instrumental and basic activities of daily living) were evaluated to predict
      functional decline (deterioration in BADL) using logistic regression models.
      Functional decline was observed in 22 (20.8%) of 106 surviving patients.
      EuroSCORE (OR per 10% increase 1.18, 95% CI: 0.83-1.68, P = 0.35) and STS score
      (OR per 5% increase 1.64, 95% CI: 0.87-3.09, P = 0.13) weakly predicted
      functional decline. In contrast, the frailty index strongly predicted functional
      decline in univariable (OR per 1 point increase 1.57, 95% CI: 1.20-2.05, P =
      0.001) and bivariable analyses (OR: 1.56, 95% CI: 1.20-2.04, P = 0.001 controlled
      for EuroSCORE; OR: 1.53, 95% CI: 1.17-2.02, P = 0.002 controlled for STS score).
      Overall predictive performance was best for the frailty index [Nagelkerke's R(2)
      (NR(2)) 0.135] and low for the EuroSCORE (NR(2) 0.015) and STS score (NR(2)
      0.034). In univariable analyses, all components of the frailty index contributed
      to the prediction of functional decline. Conclusion Over a 6-month period,
      functional status worsened only in a minority of patients surviving TAVI. The
      frailty index, but not established risk scores, was predictive of functional
      decline. Refinement of this index might help to identify patients who potentially
      benefit from additional geriatric interventions after TAVI.

PMID- 23008509
TI  - Percutaneous left atrial appendage closure for stroke prevention in patients with
      atrial fibrillation: an assessment of net clinical benefit.
AB  - AIMS: The PROTECT-AF (WATCHMAN Left Atrial Appendage System for Embolic
      Protection in Patients with Atrial Fibrillation) trial found left atrial
      appendage (LAA) closure an alternative to anticoagulation in selected patients
      with non-valvular atrial fibrillation (AF). We aim to estimate the net clinical
      benefit (NCB) of percutaneous LAA closure. METHODS AND RESULTS: Post hoc analysis
      of outcomes among 707 adults with AF in the PROTECT-AF trial and 566 in the
      Continued Access (CAP) registry undergoing LAA closure with the Watchman device
      compared with sustained anticoagulation. Outcomes were ischaemic stroke,
      intracranial haemorrhage, major bleeding, pericardial effusion, and death,
      weighted to reflect the relative impact in terms of death and disability. Net
      clinical benefit was calculated as the sum of annualized rates of these outcomes
      after intervention minus rates on warfarin. The NCB of LAA closure during 1623
      person-years follow-up in the trial was 1.73%/year (95% CI: -0.54 to 4.39%/year)
      and during 741 patient-years in the registry was 4.97%/year (95% CI: 3.07
      7.15%/year). Among patients with a history of ischaemic stroke, the NCB was
      greater in the registry (8.68%/year, CI: 2.82-14.92%/year) than the trial
      (4.30%/year, CI -2.07 to 11.25%/year). In the registry, the NCB of LAA closure
      increased from 2.22%/year (CI: 0.27-6.01%/year) in patients with CHADS(2) scores
      = 1 to 6.12%/year (CI: 3.19-8.92%/year) in those with scores >=2. CONCLUSION:
      Combining rates of thrombo-embolism, intracranial haemorrhage, major adverse
      events, and death allows objective comparison of the benefit and risk of device
      therapy vs. anticoagulation in patients with AF. The NCB of LAA closure is
      greatest for patients at a higher risk of stroke.

PMID- 23008510
TI  - Isosorbide-5-mononitrate and endothelial function: a wolf in sheep's clothing.

PMID- 23008511
TI  - Endothelial cell repopulation after stenting determines in-stent neointima
      formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial
      cell modification.
AB  - AIMS: Understanding endothelial cell repopulation post-stenting and how this
      modulates in-stent restenosis is critical to improving arterial healing post
      stenting. We used a novel murine stent model to investigate endothelial cell
      repopulation post-stenting, comparing the response of drug-eluting stents with a
      primary genetic modification to improve endothelial cell function. METHODS AND
      RESULTS: Endothelial cell repopulation was assessed en face in stented arteries
      in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment
      resulted in near-complete denudation of endothelium, but was followed by
      endothelial cell repopulation, by cells originating from both bone marrow-derived
      endothelial progenitor cells and from the adjacent vasculature. Paclitaxel
      eluting stents reduced neointima formation (0.423 +/- 0.065 vs. 0.240 +/- 0.040
      mm(2), P = 0.038), but decreased endothelial cell repopulation (238 +/- 17 vs.
      154 +/- 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the
      effects of selectively improving endothelial cell function, we used transgenic
      mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as
      a model of enhanced endothelial cell function and increased NO production. GCH-Tg
      ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates
      (0.52 +/- 0.08 vs. 0.26 +/- 0.09 mm(2), P = 0.039). In contrast to paclitaxel
      eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by
      increased endothelial cell coverage (156 +/- 17 vs. 209 +/- 23 nuclei/mm(2), P =
      0.043). CONCLUSION: Drug-eluting stents reduce not only neointima formation but
      also endothelial cell repopulation, independent of strut coverage. In contrast,
      selective targeting of endothelial cell function is sufficient to improve
      endothelial cell repopulation and reduce neointima formation. Targeting
      endothelial cell function is a rational therapeutic strategy to improve vascular
      healing and decrease neointima formation after stenting.

PMID- 23008512
TI  - One for the road...

PMID- 23008513
TI  - RNA interference-based silencing reveals the regulatory role of fatty acid
      binding protein 4 in the production of IL-6 and vascular endothelial growth
      factor in 3T3-L1 adipocytes.
AB  - The fatty acid-binding protein 4 (FABP4) is believed to play an important role in
      maintaining glucose and lipid homeostasis. However, the physiological functions
      of FABP4 in adipocytes have not been fully elucidated because of difficulties
      associated with the effective transfection of small interfering RNA (siRNA) to
      differentiated adipocytes. The aim of this study was to clarify the physiological
      roles of FABP4 in adipocytes by establishing an efficient, universal technique
      for endogenous gene silencing in fully differentiated 3T3-L1 cells. Confocal
      based three-dimensional observations demonstrated that, in traditionally cultured
      3T3-L1 cells, multilayers of undifferentiated cells were formed. As a result,
      small interfering RNA failed to reach many of the differentiated cells. To solve
      this problem, we developed a reliable method, denoted as density-based separation
      followed by replating of enriched adipocytes in a monolayer (DREAM) and, using
      the developed method, succeeded in a significant knockdown of FABP4. Loss-of
      function analyses revealed that FABP4 regulates the expression of IL-6 and
      vascular endothelial growth factor (VEGF) mediated by the protease-activated
      receptor 1 (PAR1), a thrombin receptor, in adipocytes. In addition, the basal IL
      6 production was partially suppressed by PAR1 knockdown. Moreover, we also
      demonstrated that IL-6 stimulates the proliferation of primary endothelial cells
      isolated from murine adipose tissue. These findings indicate that FABP4 may have
      a crucial role in modulating IL-6 and vascular endothelial growth factor as
      angiogenesis inducers stimulated by the cellular action of thrombin on adipocytes
      via PAR1. These findings promise to be helpful for developing an understanding of
      physiological counterparts with respect to the inflammatory and angiogenic
      properties of adipose tissue.

PMID- 23008514
TI  - Disruptions of global and JAGGED1-mediated notch signaling affect thyroid
      morphogenesis in the zebrafish.
AB  - The mechanisms underlying the early steps of thyroid development are largely
      unknown. In search for novel candidate genes implicated in thyroid function, we
      performed a gene expression analysis on thyroid cells revealing that TSH
      regulates the expression of several elements of the Notch pathway, including the
      ligand Jagged1. Because the Notch pathway is involved in cell-fate determination
      of several foregut-derived endocrine tissues, we tested its contribution in
      thyroid development using the zebrafish, a teleost model recapitulating the
      mammalian molecular events during thyroid development. Perturbing the Notch
      signaling (e.g. mib mutants, gamma-secretase inhibition, or Notch intracellular
      domain overexpression), we obtained evidence that this pathway has a biological
      role during the earlier phases of thyroid primordium induction, limiting the
      number of cells that proceed to a specialized fate and probably involving actions
      from surrounding tissues. Moreover, we were able to confirm the expression of
      Jagged1 during different phases of zebrafish thyroid development, as well as in
      mouse and human thyroid tissues. The two orthologues to the single jagged1 gene
      (JAG1) in humans, jag1a and jag1b, are expressed with different spatiotemporal
      patterns in the developing zebrafish thyroid. Both jag1a and jag1b morphants, as
      well as jag1b mutant fish line, display thyroid hypoplasia and impaired T(4)
      production; this thyroid phenotype was rescued by coinjection of human JAG1 mRNA.
      In conclusion, Notch pathway is involved in the early steps of thyroid
      morphogenesis, and Jagged1-Notch signal is required for zebrafish thyroid
      development and function. Thus, genetic alterations affecting the Notch pathway
      may confer susceptibility for thyroid dysgenesis.

PMID- 23008515
TI  - Rhesus monkey cumulus cells revert to a mural granulosa cell state after an
      ovulatory stimulus.
AB  - Follicular somatic cells (mural granulosa cells and cumulus cells) and the oocyte
      communicate through paracrine interactions and through direct gap junctions
      between oocyte and cumulus cells. Considering that mural and cumulus cells arise
      through a common developmental pathway and that their differentiation is
      essential to reproductive success, understanding how these cells differ is a key
      aspect to understanding their critical functions. Changes in global gene
      expression before and after an ovulatory stimulus were compared between cumulus
      and mural granulosa cells to test the hypothesis that mural and cumulus cells are
      highly differentiated at the time of an ovulatory stimulus and further
      differentiate during the periovulatory interval. The transcriptomes of the two
      cell types were markedly different (>1500 genes) before an ovulatory hCG bolus
      but converged after ovulation to become completely overlapping. The predominant
      transition was for the cumulus cells to become more like mural cells after hCG.
      This indicates that the differentiated phenotype of the cumulus cell is not
      stable and irreversibly established but may rather be an ongoing physiological
      response to the oocyte.

PMID- 23008518
TI  - Variation in medical practice: getting the balance right.

PMID- 23008516
TI  - Overexpression of cyclin D3 improves decidualization defects in Hoxa-10(-/-)
      mice.
AB  - Uterine decidualization, a crucial process for implantation, is a tightly
      regulated process encompassing proliferation, differentiation, and
      polyploidization of uterine stromal cells. Hoxa (Homeobox A)-10, a homeobox
      transcription factor, is highly expressed in decidualizing stromal cells.
      Targeted gene deletion experiments have demonstrated marked infertility resulting
      from severely compromised decidualization in Hoxa-10(-/-) mice. However, the
      underlying mechanism by which Hoxa-10 regulates stromal cell differentiation
      remains poorly understood. Cyclin D3, a G(1) phase cell-cycle regulatory protein
      involved in stromal cell proliferation and decidualization, is significantly
      reduced in Hoxa-10(-/-) mice. The expression of cyclin D3 in the pregnant mouse
      uterus parallels stromal cell decidualization. Here, we show that adenovirus
      driven cyclin D3 replacement in Hoxa-10(-/-) mice improves stromal cell
      decidualization. To address our question of whether cyclin D3 replacement in Hoxa
      10(-/-) mice can improve decidualization, both in vitro and in vivo studies were
      completed after the addition of cyclin D3 or empty (control) viral vectors.
      Immunostaining demonstrated increased proliferation and decidualization in both
      in vitro and in vivo studies, and in situ hybridization confirmed increased
      expression of decidualization markers in vivo. Placentation was demonstrated as
      well in vivo in the cyclin D3-replaced animals. However, fertility was not
      restored in Hoxa-10(-/-) mice after d 10 of pregnancy. Finally, we identified
      several downstream targets of cyclin D3 during decidualization in vitro via
      proteomics experiments, and these were confirmed using in situ hybridization in
      vivo. Collectively, these results demonstrate that cyclin D3 expression
      influences a host of genes involved in decidualization and can improve
      decidualization in Hoxa-10(-/-) mice.

PMID- 23008519
TI  - Risky choice in pigeons: preference for amount variability using a token
      reinforcement system.
AB  - Pigeons were given repeated choices between variable and fixed numbers of token
      reinforcers (stimulus lamps arrayed above the response keys), with each earned
      token exchangeable for food. The number of tokens provided by the fixed-amount
      option remained constant within blocks of sessions, but varied parametrically
      across phases, assuming values of 2, 4, 6, or 8 tokens per choice. The number of
      tokens provided by the variable-amount option varied between 0 and 12 tokens per
      choice, arranged according to an exponential or rectangular distribution. In
      general, the pigeons strongly preferred the variable option when the fixed option
      provided equal or greater numbers of tokens than the variable amount. Preference
      for the variable amount decreased only when the alternatives provided widely
      disparate amounts favoring the fixed amount. When tokens were removed from the
      experimental context, preference for the variable option was reduced or
      eliminated, suggesting that the token presentation played a key role in
      maintaining risk-prone choice patterns. Choice latencies varied inversely with
      preferences, suggesting that local analyses may provide useful ancillary measures
      of reinforcer value. Overall, the results indicate that systematic risk
      sensitivity can be attained with respect to reinforcer amount, and that tokens
      may be critical in the development of such preferences.

PMID- 23008520
TI  - Relations among acute and chronic nicotine administration, short-term memory, and
      tactics of data analysis.
AB  - Emerging evidence suggests that nicotine may enhance short-term memory. Some of
      this evidence comes from nonhuman primate research using a procedure called
      delayed matching-to-sample, wherein the monkey is trained to select a comparison
      stimulus that matches some physical property of a previously presented sample
      stimulus. Delays between sample stimulus offset and comparison stimuli onset are
      manipulated and accuracy is measured. The present research attempted to
      systematically replicate these enhancement effects with pigeons. In addition, the
      effects of nicotine were assessed under another, more dynamic, memory task called
      titrating-delay matching-to-sample. In this procedure, the delay between sample
      offset and comparison onset adjusts as a function of the subject's performance.
      Correct matches increase the delay, mismatches decrease the delay, and titrated
      delay values serve as the primary dependent measure. Both studies examined
      nicotine's effects under acute and chronic administration. Neither provided clear
      or compelling evidence of memory enhancement following nicotine administration
      despite reliable and systematic dose-related changes in response latency
      measures. A modest dose-related effect on accuracy was found, but the magnitude
      of the effect appears to be directly related to tactics of data analysis
      involving best-dose analyses of a very circumscribed subset of trial types.

PMID- 23008521
TI  - Resistance to extinction and relapse in combined stimulus contexts.
AB  - Reinforcing an alternative response in the same context as a target response
      reduces the rate of occurrence but increases the persistence of that target
      response. Applied researchers who use such techniques to decrease the rate of a
      target problem behavior risk inadvertently increasing the persistence of the same
      problem behavior. Behavioral momentum theory asserts that the increased
      persistence is a function of the alternative reinforcement enhancing the
      Pavlovian relation between the target stimulus context and reinforcement. A
      method showing promise for reducing the persistence-enhancing effects of
      alternative reinforcement is to train the alternative response in a separate
      stimulus context before combining with the target stimulus in extinction. The
      present study replicated previous findings using pigeons by showing that
      combining an "alternative" richer VI schedule (96 reinforcers/hr) with a "target"
      leaner VI schedule (24 reinforcers/hr) reduced resistance to extinction of target
      responding compared with concurrent training of the alternative and target
      responses (totaling 120 reinforcers/hr). We also found less relapse with a
      reinstatement procedure following extinction with separate-context training,
      supporting previous findings that training conditions similarly influence both
      resistance to extinction and relapse. Finally, combining the alternative stimulus
      context was less disruptive to target responding previously trained in the
      concurrent schedule, relative to combining with the target response trained
      alone. Overall, the present findings suggest the technique of combining stimulus
      contexts associated with alternative responses with those associated with target
      responses disrupts target responding. Furthermore, the effectiveness of this
      disruption is a function of training context of reinforcement for target
      responding, consistent with assertions of behavioral momentum theory.

PMID- 23008522
TI  - Transitivity of odor preferences: constant and particularities in hedonic
      perception.
AB  - Transitivity of preferences has been investigated for a long time in decision
      making. In the field of perception, the pleasantness of odors raises several
      questions related to individual versus cultural or universal preferences and the
      existence of a classification in a delimited hedonic space. The aim of this study
      was to test transitivity in olfactory hedonicity using a first panel of 10 mixed
      odors and a second panel of 10 odors from a delimited floral category. Data were
      collected by paired comparisons in a two-alternative forced choice. Results in
      both panels showed a strong transitivity for each participant leading to a linear
      range of 10 odors classified by preference. However, ranges varied from one
      participant to another and the mean preferences of the group did not allow one to
      infer individual's hedonic classification of odors. Moreover, the individual
      classification appeared stable over time and undisturbed by odorant distractors.
      These findings suggest that humans have considerable ability to classify odors
      hedonically as a model of individual preferences in a sensory space usually
      considered to be more involved in affective/emotional states than in cognitive
      performances.

PMID- 23008524
TI  - A missing link in the evolution of the cumulative recorder.
AB  - A recently recovered cumulative recorder provides a missing link in the evolution
      of the cumulative recorder from a modified kymograph to a reliably operating,
      scientifically and commercially successful instrument. The recorder, the only
      physical evidence of such an early precommercial cumulative recorder yet found,
      was sent to Keio University in Tokyo, Japan, in 1952 at the behest of B. F.
      Skinner at Harvard University. Last used in research in the late 1960s, the
      cumulative recorder remained locked in a storage room until 2007, when it was
      found again. A historical context for the recorder is followed by a description
      of the recorder and a comparison between it and the commercially successful
      Gerbrands Model C-1 recorder. Labeled the Keio recorder, it is a testament to
      Skinner's persistence in developing a reliable means of quantifying the behavior
      of living organisms in real time.

PMID- 23008523
TI  - Selection dynamics in joint matching to rate and magnitude of reinforcement.
AB  - Virtual organisms animated by a selectionist theory of behavior dynamics worked
      on concurrent random interval schedules where both the rate and magnitude of
      reinforcement were varied. The selectionist theory consists of a set of simple
      rules of selection, recombination, and mutation that act on a population of
      potential behaviors by means of a genetic algorithm. An extension of the power
      function matching equation, which expresses behavior allocation as a joint
      function of exponentiated reinforcement rate and reinforcer magnitude ratios, was
      fitted to the virtual organisms' data, and over a range of moderate mutation
      rates was found to provide an excellent description of their behavior without
      residual trends. The mean exponents in this range of mutation rates were 0.83 for
      the reinforcement rate ratio and 0.68 for the reinforcer magnitude ratio, which
      are values that are comparable to those obtained in experiments with live
      organisms. These findings add to the evidence supporting the selectionist theory,
      which asserts that the world of behavior we observe and measure is created by
      evolutionary dynamics.

PMID- 23008525
TI  - Spatially and Temporally Varying Associations between Temporary Outmigration and
      Natural Resource Availability in Resource-Dependent Rural Communities in South
      Africa: A Modeling Framework.
AB  - Migration-environment models tend to be aspatial within chosen study regions,
      although associations between temporary outmigration and environmental
      explanatory variables likely vary across the study space. This research extends
      current approaches by developing migration models considering spatial non
      stationarity and temporal variation - through examination of the migration
      environment association at nested geographic scales (i.e. whole-population,
      village, and subvillage) within a specific study site. Demographic survey data
      from rural South Africa, combined with indicators of natural resource
      availability from satellite imagery, are employed in a nested modeling approach
      that brings out distinct patterns of spatial variation in model associations
      derived at finer geographic scales. Given recent heightened public and policy
      concern with the human migratory implications of climate change, we argue that
      consideration of spatial variability adds important nuance to scientific
      understanding of the migration-environment association.

PMID- 23008526
TI  - Correlates of cervical cancer screening among Vietnamese American women.
AB  - OBJECTIVE: Vietnamese American women are at the greatest risk for cervical cancer
      but have the lowest cervical cancer screening rates. This study was to determine
      whether demographic and acculturation, healthcare access, and knowledge and
      beliefs are associated with a prior history of cervical cancer screening among
      Vietnamese women. METHODS: Vietnamese women (n = 1450) from 30 Vietnamese
      community-based organizations located in Pennsylvania and New Jersey participated
      in the study and completed baseline assessments. Logistic regression analyses
      were performed. RESULTS: Overall levels of knowledge about cervical cancer
      screening and human papillomavirus (HPV) are low. Factors in knowledge, attitude,
      and beliefs domains were significantly associated with Pap test behavior. In
      multivariate analyses, physician recommendation for screening and having health
      insurance were positively associated with prior screening. CONCLUSION:
      Understanding the factors that are associated with cervical cancer screening will
      inform the development of culturally appropriate intervention strategies that
      would potentially lead to increasing cervical cancer screening rates among
      Vietnamese women.

PMID- 23008528
TI  - The birth of a medical journal.

PMID- 23008527
TI  - PREPARATIVE ISOLATION AND PURIFICATION OF THREE GLYCINE-CONJUGATED CHOLIC ACIDS
      FROM PULVIS FELLIS SUIS BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY COUPLED WITH
      ELSD DETECTION.
AB  - Coupled with evaporative light scattering detection, a high-speed counter-current
      chromatography (HSCCC) method was developed for preparative isolation and
      purification of three glycine-conjugated cholic acids, glycochenodeoxycholic acid
      (GCDCA), glycohyodeoxycholic acid (GHDCA) and glycohyocholic acid (GHCA) from
      Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The separation was
      performed with a two-phase solvent system consisted of chloroform-methanol-water
      acetic acid (65:30:10:1.5, v/v/v/v) by eluting the lower phase in the head-to
      tail elution mode. The revolution speed of the separation column, flow rate of
      the mobile phase and separation temperature were 800 rpm, 2 ml/min and 25 
      degrees C, respectively. In a single operation, 33 mg of GCDCA, 38 mg of GHDCA
      and 23 mg of GHCA were obtained from 200 mg of crude extract with the purity of
      95.65%, 96.72% and 96.63%, respectively, in one step separation. The HSCCC
      fractions were analyzed by high-performance liquid chromatography (HPLC) and the
      structures of the three glycine-conjugated cholic acids were identified by ESI
      MS, (1)H NMR and (13)C NMR.

PMID- 23008529
TI  - Diet and cancer.
AB  - Environrnental and lifestyle factors, including diet, pray be responsible for the
      recognised worldwide variation in tire incidence of specific types or cancer.
      Chemical carcinogenesis is a multistage process occurring over a relatively long
      period or time. The mechanisms are complex as different factors damage develops
      following exposure to carcinogenic agents. Progression to malignancy is, at this
      stage, not inevitable. Specific agents are needed to 'promote', and induce
      'progression' or inhibit subsequent changes to develop invasive malignancy.
      Understanding the roles played by different agents and mechanisms in the overall
      carcinogenic process For cc specific cancer nary form the basis for risk
      assessment and eventual prevention. The multistep process of carcinogenesis
      including initiation, promotion, and progression, are all needed for clinically
      invasive cancer to develop. Efforts directed to any of these phases can prevent
      the development of cancer.A variety of carcinogenic and mutagenic substances ore
      present in our diet. Some are found naturally in the food ingredients, whereas
      others result from pesticide residues, environmental pollution, food additives,
      preparation and processing procedures, curd fungal contamination. The control of
      these factors may render some cancers potentially avoidable.The role of macro and
      micro-nutrients in the causation of cancer and eventually in its prevention is
      complicated by their combined distribution in food products. Intensive research
      into the nature of cancer prevention by nutrient components and their synthetic
      analogs is still in its infancy. As cancer induction, promotion and progression
      is a slow mechanism that could take many years, it is uncertain what time-period
      of dietary intake is most relevant. Currently, recommended prevention strategies
      include choose more/choose less approach, through emphasizing a shift away from
      high fat, low-fiber foods that may increase cancer risks, toward foods low in fat
      and rich in fiber and nutrients.

PMID- 23008530
TI  - Middle ear effusion in children: review of recent literature.
AB  - Middle Ear Effusion (O.M.E.) is the commonest ear problem among children, with a
      peak at the age of 2 years. Incidence varies according to geographical location
      and race variation, environmental and socio-economic factors. The disease is
      characterized by accumulation of semi-sterile secretion in the middle ear. It is
      usually due to either a dysfunction of Eustachian tube or of the mucociliary
      system or both. The most common presenting symptoms are mild to moderate
      conductive hearing loss, attacks of earache, and deterioration in school. The
      diagnosis is based on history, clinical findings and hearing assessments. In
      general, treatment is classified as conservative and surgical. Early screening
      and health education are the recent concepts advocated, for early detection.

PMID- 23008531
TI  - Systemic lupus erythematosus for general practitioners: a literature review.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disease of unknown etiology
      or etiologies.The disease may be acute or chronic. A wide clinicopathological
      spectrum is expressed in each organ involved which is induced through multiple
      antibodies that result in. imnunologically mediated tissue injury.In this
      literature review, the clinical and pathological features as well as laboratory
      abnormalities, measures /or diagnosis, outlines of management, and prognosis are
      discussed.

PMID- 23008532
TI  - The landry-guillain-barre strohl syndrome 1859 to 1992 a historical perspective.
AB  - The history of the development of knowledge about Guillain-Barre-Syndrome (GBS)
      is reviewed. The clinical profile, including characteristic CSF findings, were
      established by Laundry in 1859 and Barre in 1916. Pathologic features of GBS were
      defined ill three landmark papers by Haymarker and Kernohan in 1949, Waksman and
      Adams in 1955, and Asbury, Arnason and Adams in 1969. Although GRS is considered
      to be an immune-mediated disorder, the exact immune mechanism(s) leading to
      demyelination is riot yet well established bill probably involves both cellular
      and humoral responses. Treatment modalities have progressed from massages and
      volatile liniments used by Landry to anticipatory and supportive care, plasma
      exchange, and intravenous immunoglobulin. Outcome continues to be generally
      favorable as originally emphasized. Clinical and electrophysiologic predictors of
      unfavorable outcome have been identified.

PMID- 23008533
TI  - Enteric Fever in asir region, southern of saudi arabia.
AB  - Ninety four cases of Enteric fever seen in Asir region, in southern Saudi. Arabia
      were analyzed. 68 cases were males and 26 were females. The average age was 2.5
      years. The majority of cases were foreigners (66%), while the Saudis were only
      34%. Among foreigners, enteric fever was commonly seen in patients from the
      Indian subcontinent (47% of all cases). No significant difference was found in
      the clinical presentation of patients of different nationalities. The disease was
      generally mild and no mortality was seen. Leucopenia was fraud in only 22.2% of
      cases while anemia occurred in 12.8%. A mild reversible disturbance in the liver
      function test was seen in some patients. Abnormalities in urine analysis were
      also observed. Multi-drug resistant isolates were more commonly seen in Indian
      patients. Some drug resistance was also seen in patients from Egypt and Syria.
      The study has shown the effectiveness of aminoglycosides and cephalosporins in
      treating resistant cases.

PMID- 23008534
TI  - Knowledge, Attitudes and Practices related to Diarrhoea in Eastern Province,
      Saudi Arabia.
AB  - Community knowledge, attitudes, beliefs and practices are essential in any
      diarrhoea research. This cross-sectional study addresses these questions ill a
      semi-urban community in the Eastern Province of Saudi Arabia. The study included
      344 subjects and 276 controls v/' all age groups. Most people had reasonable
      knowledge of diarrhoea. Mothers o/' children with diarrhoea continued to fired
      them during the attack. However, some community practices were found to be
      harmful. The majority of diarrhoea cases neither sought medical attention, nor
      used oral rehydration salts (ORS) at home. Instead, they resorted to faulty self
      medication. Overall use of ORS was 53%; much less than expected. Education of
      health personnel on ORS might improve its use. It was found that the community
      needs to be educated on the benefits of hand washing before meals and after
      changing soiled diapers, washing of eggs and the use of boiled water for the
      preparation of infant preparing feeds.

PMID- 23008535
TI  - Evaluation of primary health care in riyadh, saudi arabia.
AB  - Primary health care (PHC) is a new concept in the health field. Its objective is
      to deliver integrated health service (curative and preventive). The Alama-Ata
      conference in 1978 urged countries to adopt the PHC approach to promote the
      health of all people. The expansion of PHC created the need for various types of
      evaluations (structure process and outcome).The aim, of this study is to assess
      PHC in Riyadh in terms of structure and outcome. The study was conducted at three
      PHC centers (A, B & C). The samples of the study included 300 consumers. Two
      instruments were used to collect data. Instrument I is an assessment sheet
      measuring resources in terms of availability and quality. Instrument II is a 4
      pointlikert scale measuring consumer satisfaction. Validity and reliability were
      established before data collection. Descriptive and inferential statistics were
      used.The results show that the centers' human resources do not measure up to the
      ideal standards, particularly those in center C. The clinical support areas are
      under-equipped in centers A and C. The facilities in the three centers are
      inadequate. The Majority of the consumers studied were female Saudis, illiterates
      and housewives. The majority of the consumers were satisfied with the services,
      acid no differences were found between Saudis and non-Saudis.

PMID- 23008536
TI  - Attitudes of the mildly mentally retarded children's parents toward their
      children's handicap: Dammam - Saudi Arabia.
AB  - The objectives of this case-control study was to identify the attitudes of
      parents of mentally retarded children towards the illness of their children.
      Sixty-nine parents ofrniltlly mentally retarded male children (MR group) and a
      similar number of matched parents of normal male children (Control Group) were
      interviewed using a questionnaire.The parents of the MR group had feelings of
      guilt and self-blame which was significantly higher in mothers than in fathers.
      Feeling of rejection and inferiority were reported by the parents with no
      significant difference between fathers and mothers. All of the rates, however,
      were found to be less than those reported /tom western societies. Failure of
      families to investigate causes of mental retardation was found in more than a
      quarter of all the study groups. Parents of the MR group asked for more services
      to be provided by the appropriate governmental agencies.

PMID- 23008537
TI  - Program evaluation: considerations of effectiveness, efficiency and equity.
AB  - Health programs should be effective in reaching their objectives and should do so
      through efficient use of scarce resources. Moreover, the benefits should be
      equitably distributed among the targeted beneficiaries. The individual
      desirability of these attributes of program success is unquestioned, but their
      mutual compatibility should be. Narrowly based programs might be very efficient,
      whereas expansion into more difficult areas could be costly. Moreover, the
      difficult areas are likely to comprise disadvantaged groups that are inequitably
      served at present.The paper argues that measures of effectiveness, efficiency and
      equity need to be more sharply defined, so that trade-offs in program emphasis
      can be objectively assessed. Methods of analysis that make the trade-offs clear
      are pre-sented and applied to real data taken from a family planning study in
      India.

PMID- 23008538
TI  - Perception of Infant Feeding Practices among mothers-to-be:An Urban-based school
      study.
AB  - This study on the perception of infant feeding practices was conducted among
      unmarried girls from two randomly selected Saudi public schools in Al-Khobar.
      Though it was encouraging to note that the attitude of the, girls was largely in
      favour of breast feeding, many deficiencies were identified in their knowledge of
      infant feeding. 67.1 % students were unaware of the importance of colostrum and
      70.5% opted for scheduled feeding over demand feeding. To 40.2% girls an optimum
      duration of 18-24 months for breast Feeding was not desirable. A large proportion
      of students lacked knowledge on the methods of promoting lactation such as early
      suckling (51.4%), frequent suckling (40%) and "rooming-in" (37.9%). Only 28% of
      the girls knew the correct age of introducing solid food. With the present trend
      of decline in the duration of breastfeeding in Saudi Arabia, the schools could
      play an important role in training and motivating future mothers for proper
      infant feeding practices.

PMID- 23008539
TI  - Islamic teachings and cancer prevention.
AB  - It was widely reported that 80 to 90 percent of all cancers are related to life
      style and environmental factors, which could be is some way preventable. Lung
      cancer is the most vivid example, where 80 to 85 percent of these cases are
      directly related to smoking. Worldwide tobacco smoking and chewing is responsible
      for 2.5 million deaths annually.Tobacco smoking and chewing is responsible for
      many cancers beside lung cancer, eg. cancer of the Month, cheeks, tongue, lips,
      pharynx, larynx and esophagus. It is also a contributing factor in cancers of the
      bladder, kidney, pros-tate, cervix and stomach.Islamic teachings prohibit
      smoking. There are hundreds of Fatwas (decrees) that prohibit smoking and chewing
      of tobacco since its first introduc-tion to Islamic countries ie. 100 H / 1591
      A.D.If the Muslims adhere to these Fatwas, they will eradicate a major cause for
      cancer. It will also reduce the deaths due to other lung diseases and ischemic
      heart diseases which showed relentless increase in most Islamic countries.

PMID- 23008540
TI  - The Symposium that I attended: "Hepatocellular carcinoma prevention".
AB  - A symposium on liver disease was held in Jeddah on Dec. 1992. Hepatocellular
      carcinoma (HCC) which is prevalent in hepatitis B carriers, is one of the
      malignant tumours with the highest mortality.A study conducted in Jeddah strongly
      supported the role, of hepatitis B and C in the development of liver carcinoma in
      Saudi Arabia.Since HCC, is asymptomatic in its early stages, clinical
      presentation is usually late, when the tumour is inoperable. However, the
      successful resection rate of early tumours is high. Primary prevention,
      therefore, is the goal. This includes the screening for vaccination against
      hepatitis B and should in the near future be included in health education.Early
      detection and diagnosis is possible through serology markers - serum-alfa
      fetoprotein (AFP) and GTT-isoenzymes.AFP is sensitive and inexpensive, and is
      suitable for HCC screening of hepatitis B carriers in whom its sudden rise is
      significant. Early diagnosis of HCC, at this stage, can be confirmed by
      sonography and CT scan.It is recommended that serum AFP levels be used for
      screening hepatitis B carriers in hospitals and PHC centers, in Saudi Arabia.

PMID- 23008541
TI  - Breast cancer and early detection.

PMID- 23008542
TI  - Breast cancer: attitude, knowledge and practice of breast self examination of 157
      saudi women.
AB  - INTRODUCTION: Breast cancer is the commonest cancer in Saudi females. Breast self
      examination (BSE) is a practical screening method for early detection of breast
      cancer. OBJECTIVES: The aim of the study is to find out knowledge and practice of
      BSE among Saudi women and their attitude towards breast cancer. METHODS: 157
      Saudi women were randomly selected and interviewed in the general clinics of King
      Abdulaziz University Hospital, Jeddah, and a questionnaire was used to collect
      data. RESULTS: The age range of the women was from 15 to 69 years with mean age
      of 32.5 years and median of 30 years. 80 (51%) out of 157 women were illiterate.
      19 (12%) women were found to conduct BSE, 8 (5%) regularly and 11 (7%)
      irregularly. 145 (92%) showed willingness to seek medical advice if they discover
      lumps in their breasts. The motives of these women were, a desire to reach a
      diagnosis at an early stage in the hope of cure in 120 (76%) and fear of cancer
      in 25 (16%). 11 (7%) women were unwilling to seek medical advice and the motives
      of these women were fear of cancer in 5 (3%) and shyness in 6 (4%).  CONCLUSIONS
      #ENTITYSTARTX00026; RECOMMENDATIONS: The proper technique of BSE should be taught
      to all Saudi women using all means of education either through books and
      magazines for literate women or through video films and self explanatory charts
      for illiterate women. A national campaign aimed at raising women's awareness
      about breast cancer and BSE is recommended.

PMID- 23008543
TI  - Utilisation of health services by the primary health care centres-registered
      elderly people in burraidah city, saudi arabia.
AB  - OBJECTIVE: To assess the pattern of and factors associated with geriatrics'
      utilisation of health services. DESIGN: A cross-sectional, study involving a
      random sample of 266 elderly subjects registered in the primary health care
      centres in Burraidah city, Saudi Arabia. SETTING: The primary health care centres
      in Qassim Region, Saudi Arabia. METHODS: Data was collected from PHC centres
      registered elderly subjects at their homes. Information including utilisation of
      primary health centres, hospital admissions and duration of hospital stay were
      recorded. RESULTS: The response rate was 96.7%. Twenty percent of the sample had
      not used any health services facility during the previous year. Two-thirds of
      subjects made visits to the primary health care centres, majority of them having
      made 6 visits or less. Significant factors positively associated with those
      visits were female, advancing age, and having a family. Three-quarters of the
      sample did not have hospital admissions. Significant factors positively
      associated with admissions were diabetes mellitus, hypertension, paralysis,
      advanced age, and living with a family. CONCLUSIONS: Geriatric health services
      utilisation by the study sample is affected by family ties and the high
      prevalence of chronic diseases. Subjects living alone or crippled by immobility
      may not be able to utilise available health services properly. Community based
      geriatrics services can help this vulnerable group.

PMID- 23008544
TI  - Evaluation of Antenatal Referrals from Health Centres to the Maternity and
      Children's Hospital in Dammam city, Saudi Arabia.
AB  - OBJECTIVE: To evaluate antenatal referral rates from Primary Health Care (PHC)
      centres to the Maternity and Children's Hospital in Dammam and factors affecting
      it. METHODOLOGY: Four randomly Selected Primary Health Care Centres in Dammam
      city. A sample of 135 pregnant women referred to the hospital (cases) and
      135pregnant women not referred (controls) were randomly selected. A double phase
      sampling scheme was adopted. Questionnaires regarding the characteristics of the
      general practitioners (GPs) were distributed to those GPs caring for antenatal
      patients in the 4 health centres. RESULTS: There was a variation in the referral
      rates of the five generalpractitioners from 11.5 to 21.2 per 100 antenatal
      consultation. It was found thatS certain characteristics of the GPs had an
      important influence on the referral rates. High risk factors in pregnancy were
      present in some of the controls but they were not referred.  CONCLUSION
      #ENTITYSTARTX00026; RECOMMENDATIONS: There is a variation in the referral rates
      between the GPs. There is a need to monitor and improve the quality of the
      antenatal care and the referral process. Better training of the GPs and
      implementing shared obstetric care is recommended.

PMID- 23008545
TI  - Analysis of 303 road traffic accident victims seen dead on arrival at emergency
      room-assir central hospital.
AB  - BACKGROUND: Although Rood Traffic Accident (RTA) is a noticeable common cause of
      death in Saudi Arabia, there is no published data showing the relative frequency
      of this disease as a cause of death. AIM OF THE STUDY: This study attempted to
      find out the relative frequency of RTA as a cause of death. Also, to identify age
      groups at risk as well as make some inferences from the different types of
      injuries seen. METHODOLOGY: In a period of over a four and half years, 574
      patients were seen dead on arrival at the Emergency Department of Assir Central
      Hospital, Abha, Saudi Arabia. Of these, 303 (52.8%) were victims of RTA. RESULTS:
      The 303 victims revealed a male to female ratio of 14:1, Saudi nationals of 69%
      and age range of 3 months - 85 years (mean = 34.25 years). The peak age group was
      between 21 and 49 years and the peak period of presentation at the Emergency
      Department was between 12:00 noon and 18:00 hours. The month of ten in Hegira
      Calendar represented the peak period; a significant (P<0.05) seasonal variations
      was also seen, summer being the highest. Clinical assessment of the victims
      revealed that head and neck injuries were the commonest followed by chest
      injuries. CONCLUSION: RTA is the primary cause of death among dead on arrival
      cases affecting the most active and productive age group. The study recommended
      the implementation of pre -hospital emergency medical system.

PMID- 23008546
TI  - Preliminary study on acute rheumatic Fever at high and low altitudes of asir
      region.
AB  - OBJECTIVE: The objective was to study the profile of acute rheumatic fever (ARF)
      at high and low altitudes (hot and temperate areas respectively) with particular
      attention to the influence of these differences on the frequency or severity of
      carditis. METHODOLOGY: Thirty eight children with initial attack of ARF,
      diagnosed between November 1987 and July 1995, were studied. RESULT: Twenty seven
      were living at altitude, temperate climate (group-1) while 11 were living at low
      altitudes of Tihama, hot climate (group-2). Twenty two were males and 16 were
      females. The mean age was 9.7 years. Arthritis was the commonest feature (86.8%)
      and carditis (68.4%) came second. Mitral regurgitation occurred in 96.2% of those
      with carditis, aortic regurgitation occurred in 19.2% and tricuspid regurgitation
      in 7.7%. Mitral stenosis and aortic stenosis were not encountered. A comparison
      between group-1 and group-2 showed the frequency of carditis to be 66.7% and
      72.7% respectively and the frequency of severe carditis in those affected to be
      27.8% and 25% respectively. Chorea, erythema marginatum and subcutaneous nodules
      were uncommon. CONCLUSION: The study indicates that altitude and climate may not
      affect the frequency nor severity of carditis.

PMID- 23008547
TI  - Health Profile of Balhareth area in Taif Region.
AB  - OBJECTIVE: To describe demographic, socio-economic, environmental factors and
      general health status of one of the rural and semi-urban areas around Taif city
      at the western province of the Kingdom. METHODOLOGY: A cross sectional
      multipurpose survey for 2 weeks composed of household and school surveys using
      questionnaires, anthropometric measurements and physical and dental examinations.
      RESULTS: 340 houses and 14 schools were surveyed. A higher percentage of young
      age population was found. Findings indicated a high illiteracy rate especially
      among females. Environmental status of the area was not optimum with a need for
      better services. Maternal data indicated a high fertility rate with high rate of
      unattended deliveries. Breast feeding was a common practice and children pattern
      of feeding was satisfactory. School survey revealed a lower weight and height
      compared to NCHS population and a high rate of dental caries. CONCLUSION: The
      area was not underprivileged and did not show specific endemic disease pattern.
      Improvements in the areas of sanitation, female education and school dental
      education is recommended based on the findings.

PMID- 23008548
TI  - Survival after stroke in saudis : a hospital based study.
AB  - BACKGROUND: Prognosis of stroke has been studied in various population. Factors
      adversely affecting short term survival include impaired consciousness, leg
      weakness and increasing age. AIM OF THE STUDY: In this study, the prognostic
      effects of age, sex, hypertension, diabetes mellitus and presentation in coma on
      the survival pattern of stroke patients presenting to a referral hospital, are
      reviewed. METHODOLOGY: The medical records of all patients hospitalized with
      definite stroke at King Fahd Specialist Hospital, Buraidah, for the period
      between June 1986 and June 1991, were reviewed. The Cranial CT Scans were also
      reviewed. RESULTS: One hundred and seventy four patients, 106 males and 68
      females, with a mean age of 64 years who had definite stroke were studied to
      estimate overall survival and the various risk factors influencing it. The case
      records and cranial CT scans were reviewed. CONCLUSION: The factors adversely
      affecting survival in this study, were age above 60 (P<0.04), presentation in
      coma (P<0.003) and pre-existing heart disease (P<0.0009). There was no
      significant effect on survival due to sex, hypertension and/or diabetes mellitus.

PMID- 23008549
TI  - Hemolytic-uremic syndrome in asir region.
AB  - INTRODUCTION: Hemolytic-Uremic Syndrome (HUS) is a worldwide disease and a common
      cause of acute renal failure in childhood. Recently the number of cases in our
      area seems to be increasing. AIM: The objective of this study was to look at
      epidemiology, clinical course and complications of hemolytic-uremic syndrome in
      the Southern region of Saudi Arabia. METHOD: The medical records of 24 patients
      with typical post diarrhea HUS who were seen in Asir Central Hospital (ACH)
      between January 1989 and December 1994 were retrospectively reviewed. RESULTS: Of
      the 24 patients 15 were boys and 9 were girls with sex ratio 1.7:1. Ages ranged
      from 7 months to 11 years with a mean of 38 months. Clustering of cases were
      during spring and autumn time. Shigella dysenteriae was the most commonly
      isolated micro-organism, found in the stools of 5 patients. Complications
      occurred in 8 patients (33%) in the acute phase, 5 (21%) had generalized tonic
      clonic seizures, while 2 (8%) had depressed level of consciousness. Three of the
      patients who had generalized seizures developed permanent cortical blindness. One
      patient developed chronic renal failure. One patient (4%) died in the acute phase
      after prolonged generalised seizure and coma. The mean age of the group with
      complications was 3335 months while it was 41:03 months in the uncomplicated
      group and mean platelets count was 46+/-40 * 10(9)/L and 58 +/- 35 * 10(9)/L,
      respectively. CONCLUSION: Males seem to be more affected than females and
      Shigella was the most commonly isolated organism. Cortical blindness was
      relatively more common than in other studies and patients with complications were
      generally younger and had lower platelet count than those without complications.

PMID- 23008550
TI  - Tobacco control in saudi arabia: will it work?

PMID- 23008551
TI  - Health and lifestyle: a saudi profile.
AB  - The negative effects on health by behavior such as cigarette smoking, lack of
      physical exercise, non-control of body weight and non-use of seat belts were
      empirically documented. Available findings of the various studies on lifestyle of
      the Saudi Arabian community were not encouraging. If the general health status of
      the Saudi population is to be improved, an enforcement of healthy lifestyles must
      be considered.

PMID- 23008552
TI  - Determinants of outcome among smokers in a smoking cessation program.
AB  - BACKGROUND: Tobacco consumption is now one of the most serious problems in the
      world and is receiving renewed attention in the current health promotion.
      OBJECTIVES: This study was carried out to elucidate the psychosocial and
      behavioural aspects of smokers associated with participation, attrition and
      outcome in smoking cessation programs. METHODOLOGY: This prospective cohort
      design included three hundred and twenty six smokers from the antismoking center 
      King Fahd Specialist Hospital, Buraydah, Kingdom of Saudi Arabia. The selected
      patients were subjected to a history taking, the assessment of causes of smoking,
      motives for quitting and belief problems arising from quitting; then they were
      made to join the clinic's antismoking program and were followed up after six
      months to assess the success of the program, which was measured by the rate of
      recidivism. RESULTS AND CONCLUSION: THE RESULTS SHOWED THAT THE IMPORTANT
      PSYCHOSOCIAL AND BEHAVIOURAL FACTORS AFFECTING THE SUCCESS IN QUITTING SMOKING
      WERE: previous history of an attempt to stop tension, anxiety, anger, health
      beliefs and attitudes, importance of quitting, duration of smoking, period of
      last attempt to stop and the method used. These factors can be modified in order
      to increase the likelihood of success in quitting smoking.

PMID- 23008553
TI  - Utilization of laboratory investigations: study of knowledge, attitude and
      practice among primary care physicians.
AB  - OBJECTIVES: The aim of the study was to assess the physicians' knowledge,
      attitude and practice towards laboratory services in the primary health care
      (PHC) centers at Al-Khobar area. METHODOLOGY: Five primary health care centers
      were selected out of 9 (56%) from the Al-Khobar area. Twenty physicians (33%), in
      these primary health care centers were included. A questionnaire was given to all
      physicians to explore the knowledge, attitude and practice. RESULTS: All
      physicians considered laboratory investigations an essential service that
      contributed to the management of their patients most of the time. Knowledge and
      practice of most (80% of them) regarding laboratory investigations was between
      fair to good but the attitude of 80% of them was poor since postgraduation
      experience was the only factor which influenced their practice. CONCLUSIONS:
      There has been an increase in number of Saudi physicians working in the Primary
      Health Care Centers. The quality of the current laboratory services was deficient
      according to 30% of physicians. They considered that investigations were
      essential for primary health care centers. And finally the utilization of
      laboratory tests in the Kingdom of Saudi Arabia was higher than many developing
      countries.

PMID- 23008554
TI  - Future specialty and practice intentions among saudi medical students.
AB  - OBJECTIVE: The objective of the study is the identification of the specialty
      intentions, the reason behind that choice and the preferred practice location of
      the study population. METHODOLOGY: A cross sectional study was conducted using a
      self administered questionnaire distributed at the end of the academic year 1994.
      One hundred and forty nine (149) male and 104 female graduating medical students
      representing the four medical colleges in Saudi Arabia were included RESULTS: The
      four major clinical specialties were selected by more than half of the students;
      Internal Medicine (17%), Surgery(16%), Paediatrics (14%) and Obstetrics (11%).
      Twenty seven percent were not sure of their future career choice. Primary health
      care was chosen by only 1.6% of the students. More men chose Surgery but more
      women chose Obstetrics and Ophthalmology. DISCUSSION: "Financial incentives", "no
      night duties", "social reasons" and "less responsibilities" were the less
      frequently mentioned reasons for career choice. The qualifications in view were
      mostly Canadian Board for 49% of the students and Arab Board for 48% of them. The
      most frequently preferred locations for postgraduate training were Saudi Arabia
      (56%) and Canada (40%). The majority intended to practice in hospitals (90%) and
      in cities (85%). CONCLUSION: The current drastic deficiency of trained Saudi
      Family Physicians will continue unless targeted strategies to produce more
      generalists are undertaken.

PMID- 23008555
TI  - The learning skills of undergraduates: a proposal for saudi medical education.
AB  - BACKGROUND: The problems of medical education in Saudi Arabia emanate from its
      high course content and a lack of proper integration, exacerbated by the language
      barrier. OBJECTIVE/PROPOSAL: To encourage good lasting learning habits, it is
      envisaged the need to establish training courses for learning skills. This
      training would include the development of positive attitude and reliable
      approaches to learning, learning styles, and emotional skills. It would also
      develop specific skills such as the setting and achievement of objectives, self
      assessment, group work, accessing sources of knowledge, note-taking, reading
      skills, retention skills, examination techniques and computer literacy. Teaching
      techniques, the organization of the course, assessment procedure, and the use of
      resources also affect learning. However, changes in these areas can be beneficial
      only if students have the appropriate learning skills. RECOMMENDATIONS: Research
      needs to look at the specific ways of teaching learning skills, and the effect of
      the application of such skills.

PMID- 23008556
TI  - Knowledge, attitude and practice (kap) of primary health care physicians and
      nurses towards hypertension: a study from dammam, saudi arabia.
AB  - OBJECTIVE: To evaluate the quality of management of hypertensive patients
      attending Primary Health Care Center (PHC) in Dammam city and to determine
      factors that possibly affect it. DESIGN: A cross sectional study and direct
      interview. SETTING: Dammam city. SUBJECTS: All doctors and nurses from a randomly
      selected sample of Primary Health Care Centers during April 1994. MAIN MEASURES:
      Measuring the knowledge, attitude and practice of doctors and nurses about
      hypertension management. RESULTS: Hypertension is regarded as an important health
      problem in Saudi Arabia in the opinion of majority of doctors (80'0) and nurses
      (69%). Almost half of the doctors and nurses believe that nurses are sufficiently
      qualified to measure blood pressure of patients. Most of the doctors (96.7%) and
      nurses (86%) depend merely on face-to-face education of patients Thirty percent
      of doctors and 34% of nurses think that the care for hypertensive patients in
      their Primary Health Care Centers is inadequate. CONCLUSIONS AND RECOMMENDATIONS:
      Offering on job training of both physicians and nurses on hypertension
      management. Producing a well planned protocol on the national level. Implementing
      a total quality management and medical audit system to PHC centers.

PMID- 23008557
TI  - Parasitic and bacterial infestation among food handlers in jubail, eastern region
      of saudi arabia.
AB  - OBJECTIVE: To evaluate the prevalence of parasitic and bacterial infestations
      among food handlers. DESIGN: Retrospective study. SETTING: Food handlers working
      in the Military food serving facilities in Jubail (Eastern Province of Saudi
      Arabia). METHOD: The stool samples of 881 food handlers of different
      nationalities were examined at the Armed Forces Hospital laboratory using the
      concentration method. RESULTS: A total of 194 (20%) of the workers tested
      positive for enteric microbial infestation. Helminths were the most prevalent,
      infecting 93 (10.56%) of the food handlers; followed by protozoa which affected
      65 (7.38%) food handlers; and the smallest group was infected with bacteria in 44
      (4.9%) of the food handlers. Not only single organism infection was seen
      (83.94%), but also double (14.51%) and triple (1.55%) infections. Among the
      Helminths, Ascaris lumbricoides was the most prevalent with 33 (47.14%) cases,
      Giardia lamblia was the most prevalent Protozoa with 23 (43.40%) cases, and
      Salmonella was the most prevalent bacteria with 34 (87.18%) cases. Expatriates
      from South Asia showed a significant rate of infection when compared to
      expatriates from Arabian countries. The Bangladeshi food handlers were of the
      greatest prevalence of infection with 151 (17.14%) cases, followed by Indian
      workers with 17 (1.93%) cases, and Pakistani workers with 11 (1.25%). CONCLUSION:
      The study stresses the importance of regular check-ups and prompt treatment of
      infected food handler.

PMID- 23008558
TI  - Impact of training of primary health care staff on maternity and child health
      services.
AB  - INTRODUCTION: Training of primary health care (PHC) staff, at Hail region, is
      conducted as a part of a national program for training all PHC staff all over the
      Kingdom of Saudi Arabia. The program started in Hail region during the year
      1412H. The objective of the program was to train all PHC staff, or at least a
      doctor and a nurse or a midwife in every health center, on Maternity and Child
      Health (MCH) services. This objective was achieved at Hail region by the end of
      the year 1414H. OBJECTIVES: The objective of this study is to evaluate the impact
      of training of PHC staff on maternal and child health services in Hail region.
      MATERIALS AND METHODS: Collection of data about MCH services was done by using
      structured forms, pre-tested and distributed at the end of each year studied to
      all Primary Health Care Centres (PHCCs). These forms were collected, data were
      encoded into the computer and analyzed by using SPSS for Windows statistical
      package. RESULTS: Evaluation of the program, at the end of the year 1415H, showed
      improvement in utilization of MCH services, and improved quality of care provided
      for mothers and children. This improvement was manifested by reduction of
      percentage of home deliveries without medical supervision, and increased numbers
      of risk factors discovered among pregnant mothers and children. However, the
      percentage of deliveries conducted at PHCCs were not increased, and pregnancy
      outcome showed slight reduction of S.B. rate. DISCUSSION: Improvement in the
      knowledge of the trainees was marked. Also intellectual skills e.g., using growth
      charts were markedly improved. However, because of the short duration of the
      courses, manual skills were not improved significantly. So increased frequencies
      of risk factors discovered among registered pregnant mothers and children was
      evident, however, deliveries at PHCCs were not increased. CONCLUSION: Training of
      PHC staff had a positive impact on maternal health services at Hail region.
      However, more time must be allowed to the practical part of training at the
      hospitals.

PMID- 23008559
TI  - Did the national campaign for poliomyelitis vaccination achieve its objectives? A
      pilot survey in Al-khobar area.
AB  - OBJECTIVES: To verify whether the first national campaign for poliomyelitis
      vaccination achieved its objectives. SETTING: Al-Khobar area in the Eastern
      Province of the Kingdom of Saudi Arabia.  MATERIALS #ENTITYSTARTX00026; METHODS:
      Randomized samples have been obtained using the Bowleg's proportional allocation
      scheme. At the first stage, housing blocks of 8-10 houses were selected using
      random sampling procedure. At a second stage, 2 houses from each block were
      selected in a 1 or 4 order. Both Saudi and non-Saudi nationals living in these
      households were screened using pretested questionnaire administered at a face-to
      face by trained interviewers. The questionnaire covered areas that included
      number of children vaccinated, reasons for non vaccination, whether or not the
      vaccinated child has received certificate of vaccination as well as placement of
      stickers on the door of the vaccinated households. RESULT: A total of 107
      households were surveyed in Al-Khobar. The total populations surveyed was 527
      people including 213 adults and 314 children (152 of the children were aged 5
      years or less). In all the households surveyed, all eligible children age 5 years
      or less were vaccinated. All of the vaccinated children obtained a vaccination
      certificate. CONCLUSION: The overall percentage coverage in Al-Khobar was 100%.
      This denotes the success of the campaign. A nationwide survey is suggested to
      corroborate these findings.

PMID- 23008560
TI  - Viral hepatitis, the battle continues.

PMID- 23008561
TI  - Guidelines for the management of diabetic patients in the health centers of saudi
      arabia.
AB  - This paper presents general guidelines for the management of diabetic patients
      within the primary health care (PHC) system in the Kingdom of Saudi Arabia (KSA).
      It intends to enhance PHC physicians' knowledge and improve clinical practice to
      ensure better management of people with diabetes mellitus. A stepwise (Algorithm)
      management approach for different categories of diabetic patients, including
      diet, exercise, and drugs, is suggested. The peculiarities of Family Medicine,
      e.g., adopting the biopsychosocial model, the holistic approach, and relations
      with the hospital are considered.

PMID- 23008562
TI  - Seroepidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) and
      relationship to alanine transferase (alt) in saudi workers at yanbu industrial
      city.
AB  - OBJECTIVES: To study the epidemiology of Hepatitis B virus (HBV) and Hepatitis C
      virus (HCP) in a relatively new industrial community in Yanbu, and to find out
      whether any relationship exists between increased serum Alanine Transferase (ALT)
      and HBV infection. METHOD: A group of Saudi male workers (n=332) (mean age = 32
      years) were screened for Hepatitis B core antibody (anti-HBc), Hepatitis B
      surface antigen (HBsAg), Hepatitis C virus antibody (anti-HCV), and Alanine
      Transferase (ALT) level and the results were correlated with age and marital
      status. RESULTS: Overall, the prevalence of anti-HBc, HBsAg, and anti-HCV were
      23.2%, 7.7% and 0.6% respectively. Age-related HBsAg carrier rates were 7.8%,
      6.4% and 9.4% for age groups 18-20, 21-30 and over 30 years respec-tively. Anti
      HBc positivity rates lucre 7.8%, 24.3% and 23.1 M for the same age groups. Anti
      HCV was positive in only two cases (0.6%) of all subjects. Con-sidering marital
      status, HBsAg and anti-HBc positivity rates were 7.8% and 20.5% for single
      subjects compared with 7.4% and 24.5% for married subjects (P=> 0.5 and > 0.5).
      Twenty-two percent of all subjects had ALT levels above 35 U/L with no
      correlation between the increase of ALT and anti-HBc or HBsAg positivity.
      CONCLUSIONS: THE FINDINGS OF THIS WORK: (1) Support the notion of relatively low
      prevalence of HCV in the Saudi Population as compared to HBV. (2) Provide clues
      regarding possible routes of transmission of HBV in Saudis that may help in
      vaccination policies for control of HBV infection. (3) Emphasize the fact that
      ALT level is an independent factor of HBV infection, and (4) Signify the need to
      screen industrial workers fir non-viral causes of liver disease.

PMID- 23008563
TI  - PATTERN OF HBsAg POSITIVITY IN SELECTED GROUPS AT KING KHALID GENERAL HOSPITAL -
      HAIL REGION, KINGDOM OF SAUDI ARABIA.
AB  - BACKGROUND: Hepatitis B virus (HBV) is endemic in the Kingdom of Saudi Arabia.
      The acquisition of infection occurs early in life. The availability of safe and
      efficacious vaccines has led to the feasibility of an effective control of HBV
      infection. This study compares the pattern of HBsAg positivity among selected
      groups of patients with similar groups in other regions in the Kingdom of Saudi
      Arabia. OBJECTIVES: This study is conducted to determine the prevalence of HBsAg
      positive subjects among selected groups of patients attending the main general
      hospital in the Hail region. SUBJECTS AND METHODS: This retrospective study
      included 14029 subjects that were tested for HBsAg at King Khalid General
      Hospital, during the period from April 1994 to April 1996. RESULTS AND
      DISCUSSION: The overall prevalence of HBsAg positive subjects was 3.5%. The
      prevalence for Saudis was about 3.2% for Saudis. Pakistanis had the highest
      prevalence of 11.8%. The prevalence was 3.02% for blood donors, and 2.1 % among
      pregnant women. No significant difference was found among different age groups.
      Hail region had a lower prevalence of HBsAg positive cases compared to that
      estimated by previous studies in the Kingdom, suggesting success in efforts
      applied by the Ministry of Health (110H) for prevention of Hepatitis B viral
      infection. CONCLUSION: We can conclude that the prevalence of HBsAg positive
      subjects is declining in the Hail region, Kingdom of Saudi Arabia (KSA). This
      decline suggests the success of preventive efforts such as vaccination of
      newborns with the HBsAg vaccine. However, screening of pregnant women for HBsAg
      scents to be necessary.

PMID- 23008564
TI  - Utilization of laboratory investigations in primary health care centers in Al
      khobar, saudi arabia.
AB  - OBJECTIVE: The objective of this study was to determine the pattern of
      utilization of laboratory investigations in the Al-Khobar area of Saudi Arabia.
      MATERIAL AND METHODS: A two-stage sampling design was used to select a Family
      Health Records checklist. At the first stage, 5 Primary Health Care Centers were
      selected out of 9 using a random sampling method. A Family Health Records
      checklist was selected using a systematic sampling design from each selected
      Primary Health Care Center at the first stage. RESULTS: The results showed that
      laboratory investigations were used for 49% of the sample population tested. Of
      these, 84% recorded a maximum of 3 laboratory tests. In over half of the cases,
      the tests were inappropriately utilized, 37.8% were underutilized and 13.2% were
      over-utilized. There was no significant difference in the pattern of utilization
      between males and females and between Saudi and non-Saudi patients. However,
      laboratory services were utilized more for patients above the age of 40 years,
      where an average of 2.1 tests per patient was recorded. CONCLUSION: There was a
      significant difference between primary health care centers regarding pattern of
      laboratory utilization. Respiratory disease accounted for the majority of the
      health problems, followed by diabetes mellitus and hypertension. Microbiology was
      the most heavily used investigation followed by biochemistry and hematology.
      Urinalysis was the most frequently requested test followed by blood glucose and
      complete blood count (CBC). This study highlighted the problems in the
      utilization of laboratory investigations and led to a number of solutions and
      recommendations.

PMID- 23008565
TI  - FACTORS ASSOCIATED WITH PATIENT's CARE DURING CONSULTATION IN MINISTRY OF HEALTH
      FACILITIES, JEDDAH CITY, SAUDI ARABIA.
AB  - OBJECTIVE: To assess the factors affecting health care and patient's satisfaction
      during the consultation. DESIGN: A cross-sectional study was conducted using a
      structured questionnaire form on a random sample of outpatient clinic attendants.
      SETTING: The Outpatient Department clinics at King Fahad and King Abdulaziz
      Hospital in addition to eleven Primary Health Care Centers (PHCCs) in Jeddah.
      SUBJECTS: A sample of 340 subjects attending clinics of two hospitals and eleven
      PHCCs. METHODS: Direct interviewing of subjects using a structured questionnaire
      was carried out. Information collected was basic demographic data regarding
      satisfaction with aspects of outpatient health care. RESULTS: The rate of
      patients' satisfaction in all facilities was 76.5% with no significant variation
      between hospitals and Primary Health Care Centers. The study showed aspects of
      poor patient care, such as short consultation time and incomplete physical
      examination of patients. Other factors correlated with mean consultation time and
      completeness of physical examination were stressed. CONCLUSION: There was a low
      rate of patients' satisfaction in all Ministry of Health (MOH) facilities
      studied. Aspects related to patient care need to be improved. Practical
      recommendations on this were stressed.

PMID- 23008566
TI  - The second campaign for poliomyelitis vaccination in the eastern province:
      different strategy with similar success.
AB  - PURPOSE: To determine whether the change from the door-to-door strategy of
      administering the Oral Polio Vaccine (OPV) to designated vaccination points has
      led to less than optimal vaccination coverage. METHODS: The Second Bi Annual
      Poliomyelitis Vaccination ended on 28 Rajab 1417N (9 December 1996G). To minimize
      the high cost in terms of staff and financial resources, the local authority in
      the Eastern Province offered the vaccinations at various primary health and
      commercial centers, schools and private hospitals. The WHO cluster sampling
      technique was used to conduct a survey in the Al-Khobar and Qatif areas to verify
      the percentage coverage using the new strategy. RESULTS: A total population of
      1399 including 644 adults and 755 children (317 Al-Khobar, 438 Qatif) was
      surveyed. There were 153 children aged less than 5 years in Al-Khobar and 179 in
      Qatif Of these, 148 (96.7%) in Al-Khobar were vaccinated compared to 179 (100%)
      in Qatif. Only 5 of the eligible children were not vaccinated, two of whom were
      Saudis and three non-Saudis. CONCLUSIONS: The study shows an overall percentage
      coverage of 98.4 in the Eastern Province which is well above the WHO's minimal
      80% target for success. This method of vaccination at assigned points may be used
      in areas where the literacy rate is high and public cooperation is at a maximum.

PMID- 23008567
TI  - GLANZMANN's THROMBASTHENIA-SPECTRUM OF CLINICAL PRESENTATION ON SAUDI PATIENTS IN
      THE EASTERN PROVINCE.
AB  - INTRODUCTION: Glanzmann's thrombasthenia is a rare inherited hemorrhagic disorder
      characterized by abnormal platelet function. It usually presents with
      subcutaneous bleeding and bleeding from the mucous membranes. OBJECTIVES: The aim
      of the study is to find out the clinical presentation of Glanzmann's
      thrombosthenia in Saudi patients, Eastern Province. METHODS: In this report we
      have reviewed the clinical presentation of sixteen Saudi patients suffering from
      this disorder presented at King Fahd Hospital of the University in AI-Khobar over
      a period of eleven years. RESULTS: We have noticed similarity in the frequency of
      the various symptoms with those reported in the literature except for the
      apparently more frequent hemarthrosis in our patients which mimics hemophilia.
      CONCLUSION: The spectrum of clinical presentations with Glanzmann's
      thrombosthenia appears to be wide and the occurrence of the various symptoms
      varies. Moreover, some of the presenting features tend to mimic those of
      hemophilia, a situation which, in some cases, has resulted in unnecessary
      treatment with Factor VIII-containing blood components.

PMID- 23008568
TI  - Acute life-threatening asthma in asir central hospital.
AB  - AIM: This study was conducted to analyze the severe acute asthma admissions in
      Asir Central Hospital (ACH) in Abha, Saudi Arabia. In particular, it aimed to
      identify risk factors and final outcome of acute life-threatening asthma. METHOD:
      All patients admitted to the Intensive Care Unit (ICU) with acute bronchial
      asthma from June 1989 to May 1995 were analyzed. Total admis-sions to the ICU
      were obtained to determine the prevalence of asthma admission to the ICU.
      RESULTS: There were 13 admissions for 8 patients. Three patients died and five
      were discharged in good condition. All patients received almost similar modes of
      therapy. Late presentation was the main cause of death. No patient died of asthma
      outside the ICU. Asthma constituted 0.42% of total ICU admissions. Several risk
      factors for admission to ICU were identified, including: poor compliance,
      previous requirement of systemic steroids, history of previous intubation, and
      psychiatric illness. CONCLUSION: Asthma continued to be a cause of death despite
      the availability of treatment. Late presentation is the main cause of death. With
      proper management the outcome for a majority of patients could be good even in
      acute life-threatening asthma.

PMID- 23008569
TI  - Diagnosing infection.

PMID- 23008570
TI  - Imaging of infection: a correlative and algorithmic approach.
AB  - Detection and localization of infection can still be a dilemma for both
      clinicians and imaging specialists. The list of morphologic and physiologic
      modalities is increasing with the advancement of research, expanding the
      applications of existing modalities and developing new radiopharmaceuticals for
      infection imaging.Since no single modality is appropriate for all situations,
      imaging strategy for the diagnosis of infection in both soft tissue and bone
      should be tailored for individual patients according to the detailed clinical
      data including the history of underlying and previous disease processes and the
      site of suspected infection for proper and cost effective utilization of the
      different imaging modalities.

PMID- 23008572
TI  - Palliative care for patients with advanced cancer.
AB  - The increasing life expectancy in Saudi Arabia will be accompanied by an
      alteration of the patterns of disease similar to that in Western countries. One
      of these will be cancer, the second leading cause of death in the west at
      present, where 1:3 people develop cancer during their lifetime and 1:4 die of it.
      Cancer deaths are rarely easy. The distress particularly the pain it can cause is
      legendary. Palliative care is the care and study of patients with active
      progressive far advanced disease, where cure is impossible, the prognosis
      predictably short, and the focus of care is the patient's quality of life. A
      Palliative Care Program has been developed at KFSH&RC, since 1991. This has
      broadened the spectrum of health services available to cancer patients.
      Palliative care needs to be more widely available in the kingdom to relieve an
      important cause of human suffering.

PMID- 23008571
TI  - Current trends in laparoscopic cholecystectomy.
AB  - Gallstone disease is still a major health problem worldwide. Open cholecystectomy
      was the standard treatment for symptomatic gallstones for more than 100 years.
      The introduction of laparoscopic cholecystectomy in the late 1980s has led to
      dramatic changes in the management of gallstone disease. The aim of this review
      is to equip the general practitioner with the answers to questions a patient may
      ask about the current management of gallstones.

PMID- 23008573
TI  - Drug control of hypertension in primary health care centers-registered patients,
      Al-khobar, saudi arabia.
AB  - OBJECTIVE: To assess the quality of the pharmacological control of hypertension.
      DESIGN: A cross-sectional study. SUBJECTS: Primary health care centers-registered
      hypertensive patients. SETTING: Primary health care centers in Al-Khobar, Saudi
      Arabia. METHODS: Data was recorded, using a structured questionnaire, through
      direct interviewing of patients, and from their medical records. It included
      demographic characteristics, hypertension related, and doctors'-related
      variables; and patients' utilization of other health facilities and whether they
      had other chronic diseases. RESULTS: The proportion of patients with controlled
      hypertension was 37%. It was significantly increased with age below 55 years,
      with non-Saudis, duration of treatment shorter than 5 years; and with the use of
      monotherapy. Doctors' care-related variables did not show significant variation
      with the number of controlled patients which may imply that the quality of follow
      up might not be adequate. CONCLUSIONS: The proportion of controlled patients
      cared for in the PHC centers is low. The factors associated with control were
      age, and the use of a single antihypertensive drug. The study questions the
      quality of follow-up of patients by the PHC physicians.

PMID- 23008574
TI  - The prevalence of cardiovascular risk factors among students in jeddah, saudi
      arabia.
AB  - OBJECTIVES: To determine the prevalence of cardiovascular risk factors among
      students in Jeddah, Saudi Arabia. METHODS: A cross-sectional study was conducted
      during 1994 on a sample of students selected from 49 public schools using a
      multistage stratified random sampling technique. For all students, an interview
      was conducted and anthropometric and blood pressure measurements were obtained.
      Fasting glucose and total cholesterol levels on a capillary blood sample were
      measured using Accutrend for a subsample of students. RESULTS: Of the 4042
      students selected, 71% were males and the overall mean age was 15.3 +/- 2.7
      years. After age adjustment, about 23% of the students were found overweight. In
      addition, 6.4% and 9% of the students were found to have systolic and diastolic
      hypertension, respectively, with no statistically significant difference between
      males and females. Among 1432 students, 4% of males and 2% of females had
      hypercholesterolemia (p=0.06). Hyperglycemia was found in 0.4% of males and 0.6%
      of females. Among 1834 students in the 9(th) to 12(th) grades, 6.9% of males and
      0.5% of females were current cigarette smokers. CONCLUSIONS: Since attitudes and
      behaviors that influence future health are established during childhood and
      adolescence, intervention to prevent cardiovascular diseases (in adult life)
      should take place in childhood and youth to reduce the risk factors and schools
      have a great role to play in the promotion of good health.

PMID- 23008575
TI  - Drug-susceptibility pattern of mycobacterium tuberculosis among pulmonary
      tuberculosis patients in riyadh, saudi arabia.
AB  - OBJECTIVE: To identify the pattern of drug-susceptibility of newly diagnosed
      pulmonary tuberculosis patients in Riyadh, we conducted a study on all
      Mycobacterium tuberculosis positive-culture patients admitted to Sahari Chest
      Hospital from January 1994 to April 1995. METHODS: Demographic data,
      antituberculous therapy and drug-susceptibility testing results of each patient
      were reviewed from patients' hospital records. The samples were cultured on
      Lowenstein-Jensen media and drug susceptibility was tested by Bactec 12B
      (Middlebrook 7H12) media against selected antituberculous drugs RESULTS: Drug
      susceptibility was performed on 362 (91%) of the sputum positive-cultures. The
      overall initial resistance rate (1 or more drugs) was 12.4%. Initial. resistance
      was more common with a single drug (9.4%), followed by two drugs (2.3%) and then
      three drugs (0.3%). Resistance to isoniazid was most common (10.4%), followed by
      streptomycin (2.7%), rifampicin (1.9%) and ethambutol (0.6%). Single isoniazid
      resistance was 60%, followed by two drugs: streptomycin and isoniazid (13.3%).
      CONCLUSION AND RECOMMENDATIONS: Resistance to multiple drugs is not yet a
      significant problem in Riyadh. A continuous monitoring of drug resistance is
      important for planning and assessing the national TB control program. Timely and
      complete reporting is essential to identify the problem as and when it begins.

PMID- 23008576
TI  - Infantile hydrocephalus in southern saudi arabia.
AB  - OBJECTIVE: To study the prevalence and causes of infantile hydrocephalus.
      METHODOLOGY: Retrospective study of cases of infantile hydrocephalus comparing
      results with regional and international trends. RESULTS: Infantile hydrocephalus
      (IH) affected 62 infants from among 87,127 registered total live births giving an
      overall incidence of 0.71/1000. Eighteen cases (29%) with spinal dysraphism, 15
      cases (24%) with acqueductal stenosis, 9 (14.5%) post meningitis, 6 (9.7%) post
      haemorrhagic, 6 (9.7%) with structural Central Nervous System (CNS) anomalies
      (holoprosencephaly 2, hemispheric cysts 2, brain dysgenesis 1, and vascular
      anomaly 1), 3 (4.9%) congenital idiopathic, 2 (3.2%) Dandy-Walker malformation, 2
      (3.2%) toxoplasmosis and one case (1.6%) achondroplasia. Prenatal factors
      accounted for 46 cases (74.2%) of this series, while postnatal factors accounted
      for 16 cases (25,8%). Of the latter group, 9 (14.5%) were due to meningitis while
      6 (9.7%) were post haemorrhagic. Of the postnatal group there were 8 preterm
      babies (4.7% of the total series and 53.3% of the postnatal group). CONCLUSION:
      While the incidence of infantile hydrocephalus in this region remains
      statistically unchanged, new characteristics have emerged. It is interesting to
      notice the increased number of premature babies in the postnatal group. More
      associated CNS malformations have been noticed in the prenatal group. Still
      prenatal causes form the bulk of all cases.

PMID- 23008577
TI  - Spontaneous expulsion of intrabronchial metallic foreign body: a case report.
AB  - Inhalation of metallic foreign bodies is a rare event occurring mostly in
      children, and often requires early surgical intervention to avoid complications.
      We report a case of spontaneous expectoration of an intrabronchial metallic nail
      in an adult, 2 hours after inhalation.

PMID- 23008578
TI  - The validation of the general health questionnaire (ghq-28) in a primary care
      setting in saudi arabia.
AB  - OBJECTIVE: The objective of this study was to validate an Arabic version of the
      General Health Questionnaire (GHQ-28) in a primary care setting in Saudi Arabia.
      METHODOLOGY: A total of 60 Saudi patients selected by means of systematic random
      sampling were asked to fill out the GHQ-28 Arabic version. The psychiatrist
      interviewed all patients using the Arabic version of the Clinical Interview
      Schedule (CIS). RESULTS: The best cut-off level for the GHQ-28 indicating best
      trade-off between sensitivity and specificity was 4/5, where the validity values
      were, sensitivity; 72%, specificity; 74%, positive predictive value; 72%,
      negative predictive value; 74% and misclassification rate; 27%. The correlation
      coefficient was r = +0.61 and the Spearman's Rank-difference correlation was rs =
      +0.57. The area under the ROC Curve was 69%. The cut-off point 4/5 in this study
      is the same as recommended by others in primary care settings. Although the
      validity parameters are relatively low, they are within the range found by other
      studies in USA, UK and developing countries. This supports the suggestion to
      develop an Arabic Screening Questionnaire based on the translated GHQ with the
      addition of culturally specific items. CONCLUSION: The GHQ-28 Arabic Version is a
      valid instrument that may be of great help to primary care doctors in improving
      detection of psychiatric morbidity and in epidemiological research.

PMID- 23008579
TI  - Promotion of mental health as a function of different service agencies.
AB  - INTRODUCTION: There is a reliable evidence that personnel working in a variety of
      settings beyond mainstream mental health services can make an important
      contribution to the prevention of mental health problems. AIM: To assess the
      ability of personnel in different sectors including schools, school health unit
      and Primary Health Care (PHC) centers to recognize the risks and signs of
      deteriorating mental health among vulnerable people. The roles played by these
      personnel in the area of mental health were also defined. METHODS: A descriptive
      approach was used to carry out this study in different service agencies located
      in Abha region. These included female secondary schools, female school health
      units and all PHC centers. Questionnaires were mailed to teachers, physicians and
      nurses. The questionnaires contained queries about warning signs of poor mental
      health and high-risk groups for mental disorders. RESULTS: It was shown that 50%
      of school teachers in the sample were good at picking up signs of mental distress
      while others felt that they did not have the skills in this field nor was it
      their role to do so. The majority of physicians and nurses (66.03%) in school
      health unit and PHC centers identify family problems as predictor of mental
      disorders. From the stand point of the primary care provided by health centers,
      early diagnosis of cases and provision of treatment were considered unimportant
      compared to the role of case referral as stated by 15.38% and 53.84% of workers,
      respectively. RECOMMENDATIONS: It is recommended that the role of these services
      be expanded to develop skills in dealing with common mental problems.

PMID- 23008580
TI  - A study of riyadh hospitals non-urgent surgery waiting lists: from the
      physicians' perspective.
AB  - OBJECTIVE: To examine and compare the factors causing long waiting lists for non
      urgent surgery in public (Ministry of Health, military, and teaching) and private
      hospitals in the city of Riyadh, Saudi Arabia, and to examine the relationship
      between the personal characteristics of the respondents (surgeons) and the
      surgery-delay experience. MATERIAL AND METHODS: The instrument used in this study
      was a self-administered questionnaire. Out of 500 distributed questionnaires 320
      valid responses were returned. Data were collected from 14 public and private
      hospitals in Riyadh City. Frequencies and percentages; Mann-Whitney; Kruskall
      Wallis one way ANOVA; Chi-square; Phi; and Cramers' V tests were used in the
      statistical analysis.. RESULTS: Results show that seven factors were
      significantly important in causing long waiting lists. A significant difference
      with regard to the seriousness of this problem was found between the two types of
      hospitals. CONCLUSION: This study shows that there is a significant difference in
      the seriousness of the problem between private and various types of public
      hospitals. Similar studies in different parts of the country are therefore
      recommended.

PMID- 23008581
TI  - Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy
      induced oral mucositis in non-neutropenic cancer patients.
AB  - OBJECTIVE: The study was designed to assess prospectively the efficacy of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of
      chemotherapy-induced oral mucositis in non-neutropenic cancer patients. MATERIAL
      AND METHODS: In a prospective open study, adult cancer patients with chemotherapy
      induced, neutropenia-independent oral mucositis were treated with GM-CSF
      (Schering Plough Corporation, Kenilworth, NJ) prepared as mouthwash solution (5
      to 10 MUgm /ml). GM-CSF was administered within 24 hours of occurrence of oral
      mucositis at a frequency of 4 to 6 times daily. Systemic GM-CSF was not
      permissible. Oral mucositis was graded according to the modified Radiation
      Therapy Oncology Group criteria. RESULTS: Forty-nine patients were recruited but
      nine were subsequently excluded as they experienced neutropenia during GM-CSF
      therapy. The remaining 40 patients were all evaluable. Most patients had either
      Grade 3 or 4 gross (71%) or functional (70%) mucositis. The mean +/- SEM gross
      oral mucositis scores for all 40 patients combined decreased from 3.3 +/- 0.11 at
      baseline to 2.1 +/- 0.12 (p<0.0001) after 2 days, 0.95 +/- 0.11 (p<0.0001) after
      5 days and 0.23 +/- 0.07 (p <0.0001) after 10 days of therapy. Likewise, the mean
      +/- SEM functional oral mucositis scores decreased from 3.03 +/- 0.13 at baseline
      to 1.58 +/- 0.13 (p<0.0001) after 2 days, 0.68 +/- 0.11 (p<0.0001) after 5 days,
      and 0.15 +/- 0.06 (p<0.0001) after 10 days of therapy. The duration of severe
      oral mucositis was also shortened as Grade 0 or 1 (gross mucositis grading score)
      was evident in 12 (30%), 29 (73%), and 40 (100%) patients by the 2(nd), 5(th) and
      10(th) day of therapy, respectively. Similarly, Grade 0 or 1 (functional
      mucositis grading score) reported in 19 (48%), 31 (78%), and 40 (100%) patients
      by the 2(nd), 5(th) and 10(th) day of therapy, respectively. The use of GM-CSF
      mouthwash was not associated with any apparent ill effect. CONCLUSION: GM-CSF
      mouthwash as used in this study has a significant recuperative efficacy on the
      severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large
      randomized, placebo-controlled study is warranted to ascertain that benefit and
      determine the optimal dosage and schedule.

PMID- 23008582
TI  - Hyperlipidemia and obesity among diabetics at jubail miiltary hospital.
AB  - OBJECTIVE: Evaluate the pattern of dyslipidemia and obesity among diabetics,
      attending the Primary Care Clinic. SUBJECTS AND METHODS: All diabetics (282)
      registered in the Primary Care Clinic of the Armed Forces Hospital at King
      Abdulaziz Naval Base, Jubail, Eastern Saudi Arabia, were interviewed by primary
      care doctors. Weight and height were recorded; fasting blood glucose and
      cholesterol levels were measured after 12-hour fasting. RESULTS: The study
      revealed that among 89.7% type 2 and 10.3% type 1 diabetes mellitus, 22.7% had a
      normal Body Mass Index (BMI) 40.8% were overweight, and 36.5%, obese. Females had
      a significantly higher BMI than males (P<0.001). Total cholesterol was more than
      normal in 26%, LDL in 27% and Triglycerides in 11% but HDL lower than normal in
      38%. However, mixed hyperlipidemia was seen in 5% of the study population.
      CONCLUSION: Obesity and dyslipidemia were high among diabetic patients and
      special attention is required in prevention and treatment.

PMID- 23008583
TI  - Cigarette smoking behavior among South african Indian high school students.
AB  - OBJECTIVE: The aim of the study was to assess the knowledge, attitude and
      practice of cigarette smoking behavior (CSB) in a sample of Indian matriculation
      students. METHODOLOGY: All (N=325) Indian matriculation students, at high
      schools, in Northern Kwa-Zulu Natal, South Africa, were included in the study. A
      questionnaire was administered to assess knowledge, attitudes and practice of
      CSB. RESULTS AND CONCLUSION: The study showed a prevalence of 16.9%. Most smokers
      (98.2%) had commenced the practice after the age of 10 years. The most common
      reason given for CSB was experimentation (83.6%). Main influence was family
      members followed by teachers and advertisements. The association between smoking
      and lung cancer was well-known by smokers (90.7%). There was very little
      awareness of anti-smoking programmes or organizations. Alarmingly, there was
      little formal health education on the dangers of smoking in schools. The
      implications of these results are discussed and recommendations on decreasing CSB
      are made.

PMID- 23008584
TI  - Breastfeeding practice in dammam area of saudi arabia.
AB  - OBJECTIVES: The main objective of this study was to determine the breastfeeding
      status for children under 24 months and assess the causes of breastfeeding
      failure among those mothers who do not breastfeed their babies. METHODOLOGY: This
      study was conducted on a sampled population of 1185 children under 24 months of
      age, using breastfeeding indicators recommended by World Health Organization, for
      assessing breastfeeding practices within a recall period of 24 hours, in the
      Dammam area of Saudi Arabia. RESULTS: The exclusive breastfeeding rate and
      predominantly breastfeeding rates were 33% and 11.5%, respectively, under 4
      months of age among these children. The timely complementary feeding rate was
      31.7% only. All the values were far behind those recommended. The reasons given
      in order of their frequencies by the mothers for failure to breastfeed were
      insufficient milk, advice and example of other mothers and formula milk
      advertisement. CONCLUSION: This study recognizes the low level of exclusive
      breastfeeding among children under 4 months of age and lays emphasis on changing
      the behavior of mothers towards exclusive breastfeeding. This can be achieved by
      special integrated community-based approaches among potential mothers by
      supporting them after delivery and proper follow-up, to prevent failure of milk
      formation and discontinuation of breastfeeding.

PMID- 23008585
TI  - Referral from primary care to hospitals in saudi arabia: 1) quality of referral
      letters and feedback reports.
AB  - BACKGROUND: Referral between primary care and hospitals is of great importance
      for patient care and follow-up. This study was conducted because of the
      importance of the quality of referral letters and feedback reports. OBJECTIVES:
      To evaluate the quality of referrals from primary health care (PHC) centers to
      general hospital in four regions in Saudi Arabia. METHODS: This was a cross
      sectional study of a random sample of referrals from the PHC centers. The first
      sampling unit was the general hospitals to which the health centers refer. A
      random sample of health centers was then selected based on their distance from
      the hospitals. This was followed by randomly selecting 30 referrals from each
      health center. The referral letters and the corresponding feedback reports were
      then studied for quality by scoring the components of each. The data was entered
      in a personal computer using the Stat Pack Gold Statistical Package. The chi
      square was used to compare the different scores across the regions and T-test was
      used to compare the cumulative scores. MAIN OUTCOME MEASURES: The quality of
      referral letters and feedback reports was defined according to the standardized
      components using a scoring system. RESULTS: The most frequently mentioned items
      in the referrals were demographic data (100%), specialty referred to (93.3%) and
      reason for referral (82.7%). Other important items in the feedback reports
      including the name of the treating physician (81.8%), diagnosis (86.0%), and
      decision on follow-up (80%) were missing. The quality of referral letters was
      poor in 23%, with 81% as the corresponding figure for the feedback reports with
      some variation between the different regions. CONCLUSIONS: The quality of
      referral letters and feedback reports is poor and needs to be improved. This can
      be achieved through implementing the quality assurance programme.

PMID- 23008586
TI  - Factors influencing patients' utilization of primary health care providers in
      saudi arabia.
AB  - OBJECTIVE: To determine the factors that significantly discriminate between
      Ministry of Health (MOH) and private primary health care patients in Riyadh City,
      Saudi Arabia. METHODOLOGY: Through a self-administered questionnaire, data were
      collected from 408 randomly selected patients in five MOH primary health care
      centers and five private dispensaries. Data collection was conducted from
      February 15 to March 15, 1998. Two-group stepwise discriminant analysis was
      utilized in analyzing the data. RESULTS: Seven of the 33 factors were found to be
      statistically significant in discriminating between MOH and private patients.
      These factors were: (1) source of payment, (2) availability of other sources of
      income, (3) distance between residence and Primary Health Care (PHC) provider,
      (4) education, (5) preference for similar-gender doctors, (6) preference for
      Saudi doctors, and (7) perceived quality of medical staff. CONCLUSION: The study
      notes that PHC providers cannot control the sociodemographic characteristics of
      patients. Therefore, policy makers should focus on ensuring that PHC facilities
      have enough male and female doctors. Furthermore, the quality of the medical
      staff of these facilities should be upgraded to improve the overall quality of
      the services they provide. The conduct of further studies related to the
      utilization of health care providers is also recommended.

PMID- 23008587
TI  - Trends in perinatal mortality at king fahd hospital of the university, Al-khobar,
      saudi arabia: a ten years study.
AB  - OBJECTIVE: The aim of the study is to identify the major causes of perinatal
      mortality and to determine the main maternal factors which affect perinatal
      mortality at the King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi
      Arabia. METHODS: A retrospective study was conducted covering a period of ten
      years from January 1987 to December 1996. All 548 perinatal deaths, which
      occurred during that period, were analyzed according to Wigglesworth
      classification. RESULTS: The study revealed a perinatal mortality rate of
      19.2:1,000 births. Lethal malformations accounted for 116 (21.1%) of fetal
      deaths. Of the remaining 432 deaths, 214 (49.5%) occurred antenatally, 71 (16.5%)
      in labour and 147 (34%) within the first week of delivery. Amongst the normally
      formed babies, low birth weight was the commonest cause of death (29%) followed
      by the consequences of maternal diseases (14.8%). The cause of death was unknown
      in 17.3% of mature babies who died. Unbooked patients were responsible for 72% of
      the total perinatal deaths. CONCLUSION: Reduction of the perinatal mortality rate
      is possible when all women begin to value preconception counselling and
      attendance at antenatal clinics.

PMID- 23008589
TI  - Hereditary blindness: a genealogical study among Al-gharahir, a jordan valley
      tribe.
AB  - BACKGROUND: Hereditary diseases form an omnibus problem in Arab societies in
      general and in rural Arab societies in particular. AIM: Study of hereditary
      blindness and its relation to endogamous marriage among the Gharaghir tribe in
      the Jordan valley. METHODOLOGY: The researchers carried out a fieldwork among the
      Gharaghir tribe in Al-Sawalha (the northern valley region, Deir Alla, the
      Hashemite Kingdom of Jordan) using participant observation, and intensive
      focussed interviews, in addition to the genealogical method. We gathered data on
      endogamous marriages, blindness, genealogy and the degrees of kinship between the
      spouses. RESULTS AND DISCUSSION: The results show that blindness among the
      Gharaghir was found to be associated with endogamous marriage. Marriage among the
      established ancestors of the clans used to be exogamous and kinship was unilineal
      patrilineal. Through the shift to endogamy (marriage between close kin) there was
      a shift from uniliny (patriliny) to bilineal descent. This may have increased the
      probability of a recessive gene transmission from both parental sides. This is
      evidenced by the high inbreeding coefficient of 0.0687, one of the highest
      recorded.

PMID- 23008588
TI  - The prevalence of indices of hepatitis C and B infection, and elevated
      aminotransferase enzymes in patients with oral lichen planus (olp) in eastern
      saudi arabia.
AB  - OBJECTIVE: To determine the possibility of any association between HBV, HCV,
      elevated aminotransferase enzymes and Oral Lichen Planus (OLP)patients in Eastern
      Saudi Arabia. DESIGN: Sera were collected from OLP patients, to be tested for
      HbsAg, anti-HCV and ALT/AST levels. SETTINGS: All the patients who were diagnosed
      clinically in periodontal section, Dammam Central Hospital were from Eastern
      Saudi Arabia. The histopathological diagnosis was done in Histopathology Section,
      Dammam Regional Labs, the virological studies in the Virus Diagnosis Lab of
      Dammam Regional Labs and Blood Bank, and the aminotransferase tests done in the
      Dammam Central Hospital Labs. SUBJECTS: 34 serum specimens were collected from
      OLP patients, and 32 other samples from healthy populations of the same age and
      sex as the controls of the study. RESULTS: Incidence of HBsAg, anti-HCV,
      HBsAg+HCV, and elevated aminotransferase enzymes among OLP patients were 8.8%,
      14.7%, 2.9%, and 47.05% respectively and the results from the control subjects
      were 6.25%, 3.12%, 0%, and 3.12% respectively. CONCLUSION: There is a significant
      association between OLP and HCV infection. No clear evidence of this relationship
      appeared with HBV. All the aminotransferase elevated samples were positive to
      HCV, giving a clear evidence of the association of chronic HCV infection with the
      OLP. Aminotransferase elevated results could be used as a clue to clinical signs
      of asymptomatic hepatopathies, and as a marker to check the OLP cases for the
      relevant Hepatic Viruses. Despite the limited number of OLP patients in this
      study, the results could highlight the problem in this geographical area of the
      world. We recommend a comprehensive study to be carried out using this current
      study as a preliminary one.

PMID- 23008590
TI  - Choosing a medical career: what influences secondary school female graduates?
AB  - OBJECTIVE: To assess attitudes and reasons of secondary school female students
      for choosing medicine as a career. DESIGN: A cross-sectional study with a sample
      of 191 female students, who responded to an administered questionnaire. RESULTS:
      The mean age of the students was 18.3 +/- 0.94. The mean general average test
      scores for female students who applied to medicine, MLT and Nursing was 94.02%,
      91.26% and 86.78% respectively. Personal interest was the main reason in 85.7% of
      the applicants. Only 109 students (57.1%) of the study group have any knowledge
      about the profession of Medicine. One hundred sixty one of the students (84.3%)
      expected difficulties in their studies. CONCLUSION: The study showed that
      personal interest was the main reason behind the students' choice. A sizable
      proportion had no knowledge of the specialty they opted for, while more than 80%
      of the applicants anticipated some difficulties upon entering the Medical
      College. The majority of MLT applicants were not interested in nursing as a
      specialty. The current strategy for educating secondary school female students
      about Medical College programmes should be strengthened.

PMID- 23008591
TI  - Hiv/Aids knowledge in youth: the need for school health programmes.

PMID- 23008592
TI  - Impact of health education program on knowledge about AIDS and hiv transmission
      in students of secondary schools in buraidah city, saudi arabia: an exploratory
      study.
AB  - BACKGROUND: Accurate information about Acquired Immunodeficiency Syndrome (AIDS)
      and Human Immunodeficiency Virus (HIV) is important for their prevention.
      OBJECTIVES: This study is intended to assess knowledge on AIDS in students of
      secondary schools in Buraidah city and to measure the effect of a health
      education program on their knowledge about AIDS in general, modes of HIV
      transmission and the degree of their misperception about the transmission of the
      disease through casual contact. METHODOLOGY: A well-designed health education
      program using personal communication and visual media techniques was conducted
      for 483 secondary school students in Buraidah secondary schools during the year
      1997. Pre and post-tests were done to examine their knowledge about AIDS. RESULTS
      AND RECOMMENDATIONS: The results of this study pointed out that a health
      education program on AIDS for students of secondary schools greatly and
      significantly improved their scores on general knowledge on AIDS views on its
      transmission and misperception of AIDS (p<0.01). Continuous in-service programs
      for secondary students are recommended.

PMID- 23008593
TI  - Peak expiratory flow rate in a sample of normal saudi males at riyadh, saudi
      arabia.
AB  - OBJECTIVE: To find out the normal peak expiratory flow rate for adult Saudi males
      and to compare our standards with British standards. METHODS: A cross-sectional
      study was carried out in five primary health care centers representing Riyadh
      city in the period between 15(th) November through December 1993. Six hundred and
      eighty Saudi men who satisfied stringent criteria of normality were included in
      the study. RESULTS: The mean and standard deviation of the subjects' age and
      height were 28.4 +/- 13 and 167.6 +/- 6.4 respectively. Linear regression
      analysis was performed through step-wise procedure to determine the form of
      regression of peak expiratory flow on age and height. Regression curves were
      obtained and it was found that peak expiratory flow rate did not begin to decline
      until about the age of 25 years; and as height increased the peak expiratory flow
      rate increased in a linear relationship. CONCLUSION: It was demonstrated that our
      study group had lower peak expiratory flow rate compared with British people.
      These findings will serve as a basis for preparing flow rate values for our
      population.

PMID- 23008594
TI  - Ability of adult patients to predict absence or presence of Fever in an emergency
      department triage clinic.
AB  - INTRODUCTION: Fever is the most appreciated manifestation of disease which
      usually raises high therapeutic expectations. Patients seek medical advice
      because they think they are sick and feverish. If they feel that they are sick
      but not feverish, they may not seek medical advice. Subjective fever may also be
      an important clue to further evaluation of the patient. OBJECTIVE: The aim of
      this study was to assess the reliability of adult patients to predict absence or
      presence of fever in Emergency Department triage clinic. METHODS: A prospective
      study of 1241 ambulatory adult patients (above 12 years of age) was carried out
      over a three-week period. All patients were asked whether or not they had fever
      or felt they had fever or were running a temperature before oral temperature was
      taken with an IVAC digital machine. Two sets of temperature readings were taken
      to define fever as 37.8 degrees C or greater, and 38.0 degrees C or greater.
      RESULTS: The sensitivity and specificity of detecting fever by subjective means
      was 89.6% and 94.5% for male and 90.0% and 94.8% for female. The accuracy rates
      were 93.9% and 94.6% respectively. The prevalence of objective fever was 8.7%
      yielding general positive and negative predictive values of 80.9% and 98.9% with
      an accuracy rate of 94.2%. CONCLUSION: The reliability of adult patients
      attending triage clinic in assessing subjective fever was found to be good. Four
      out of five of our patients who believed they had a fever were actually found to
      have an objective temperature increase (38.0 degrees C or greater). This means
      that medical staff should take a complaint of subjective fever in our population
      more seriously.

PMID- 23008595
TI  - Knowledge, attitude and practice of primary health care doctors and nurses in
      hypertension of pregnancy.
AB  - OBJECTIVE: To assess the status of knowledge, attitude and practice (KAP) of
      doctors and nurses in Primary Health Care (PHC) centers with regard to
      hypertension in pregnancy and to identify factors associated with KAP in Al
      Khobar, Saudi Arabia. METHODOLOGY: Using a self-administered comprehensive
      questionnaire, all available doctors and nurses in PHC centers of the Al-Khobar
      area were approached to determine their knowledge, attitude and practice in
      hypertension during pregnancy. Questionnaires were validated and pilot tested.
      Each section of the questionnaire was scored and the mean scores calculated.
      Factors affecting each section were identified by means of multiple regression
      analysis. RESULTS: A total of 36 doctors and 91 nurses were enrolled in the
      study. Saudis formed 22.2% of the doctors and 47.3% of nurses. Mean years of
      practice after graduation were 12.6 and 8.7 years for doctors and nurses,
      respectively. Saudi nurses spend only 3 weeks in the obstetrics ward during the
      whole period of their internship. All Saudi nurses hold only diplomas and not
      many courses on the hypertensive disorder are offered to both doctors and nurses
      after graduation. The practice of doctors particularly in the management of
      patients after reaching a diagnosis and educating them on diet and salt intake
      was poor. Furthermore, their knowledge was also poor. Though their level of
      knowledge was poor, the nurses' practice was satisfactory, particularly in taking
      history and physical examination. The attitude of both doctors and nurses towards
      hypertensive disorders was in general, positive and satisfactory towards health
      education. Nurses' nationality and duration of post-internship training were the
      factors that influenced their attitude and scores on knowledge. CONCLUSION AND
      RECOMMENDATION: The study revealed that both doctors and nurses working in the
      PHC lacked training and knowledge in this area of their work. It is therefore
      necessary to give PHC doctors and nurses refresher courses on common and serious
      problems like hypertension. A longer period of training in action management is
      needed to improve the knowledge and practice of doctors and nurses working in
      antenatal clinics in this area.

PMID- 23008596
TI  - An unusual presentation of tuberculous splenic abscess.
AB  - A 55-year-old male presented with painful lobulated mass on the left lateral
      lower chest and upper abdomen. Evaluation revealed the mass as a subcutaneous
      abscess originating from and communicating with a splenic abscess. The patient
      was treated by incision and drainage of the subcutaneous abscess along with
      splenectomy, and antituberculous therapy. Histopathological examination of the
      spleen confirmed the diagnosis of splenic tuberculosis. Postoperatively, the
      patient improved, and was discharged ten days later on antituberculous drugs. One
      year later, the patient remains asymptomatic and shows progressive improvement.

PMID- 23008597
TI  - Factitious disorder in saudi arabia: a report of two cases.
AB  - Factitious disorders are characterized by physical or psychological
      manifestations that are intentionally produced or feigned with no apparent
      external incentives in order to assume the sick role. These disorders are rarely
      reported or may be under-reported in Saudi patients. We describe here two male
      and female Saudi cases of such disorders. Both presented predominantly with
      features of Munchausen's syndrome. Like most psychiatric patients both had sought
      help from traditional healers prior to their reporting to the hospitals. Inspite
      of the socio-cultural factors, it is clear that doctors' awareness and acceptance
      of the possibility of factitious disorders is a prerequisite to making the
      diagnosis.

PMID- 23008598
TI  - Food: the way to health or disease.

PMID- 23008599
TI  - Are young arab women eating a healthy diet? A qualitative dietary study among
      college hostel students.
AB  - BACKGROUND: Two recent studies conducted on young College Arab Women showed a
      trend towards over nutrition. It is well known that good eating habits adopted
      early in life not only improve health and control obesity in the youthful years
      but also promote healthy eating behaviours in later life. OBJECTIVE: To
      investigate the dietary habits of young college women and identify specific areas
      for nutrition education. METHODS: A self-administered questionnaire containing 20
      items related to qualitative dietary history was distributed to all the college
      (King Faisal University, Dammam) women residing in the hostel during a one-week
      period in April 1998. RESULT: Out of a total of 56 women, 50.7% frequently missed
      out on breakfast and lunch. To satisfy their state of hunger, frequent snacking
      with deserts/carbohydrate-rich food items (21.4%) and consumption of regular cola
      drinks (32.1%) was common. Fast food rich in fat and calories from restaurants
      was popular among a majority (98.2%) of the students. On the other hand, there
      was a deficient intake of protective foods and nutrients for repair, maintenance
      and growth, such as fruits (73.2%), vegetables (85.6%), milk and milk products
      (66.1%) and protein-rich foods (82.1%). CONCLUSION: To decrease the risk of
      malnutrition among young college women, there is a need to target them for
      nutrition education and adoption of healthy eating practices within the context
      of a healthy life style.

PMID- 23008600
TI  - The future of academic medical centers in saudi arabia: difficulties encountered
      in a teaching hospital.
AB  - OBJECTIVE: The objective of this study was to define and analyze the major
      difficulties experienced and documented in a university teaching hospital.
      METHODOLOGY: The academic medical center (AMC) reviewed was the King Fahd
      Hospital of the University (KFHU), Al-Khobar, Eastern Saudi Arabia. Data sources
      included student registration figures, budget allocation and the hospital annual
      reports. The retrospective analysis was restricted to difficulties encountered.
      RESULTS: While numbers of medical students increased, staff positions remained
      static. There was remarkable budgetary deficiency over 9 years; especially for
      pharmacy, equipment's and supplies. The number of patients' visit markedly
      increased. The difficulties encountered were 237 in 70 sections of KFHU. Other
      problems included recruitment difficulties and the triple role for the faculty;
      teaching, researching and service. CONCLUSION: The role of leadership is
      emphasized to provide answers for the problems; to manage AMC's more efficiently;
      to find ways of providing medical care more cost-effectively and to generate more
      funds.

PMID- 23008601
TI  - Factors affecting child development in madinah, saudi arabia.
AB  - INTRODUCTION: This paper addresses an important pre-requisite for promoting child
      health; namely the promotion of sound child development. OBJECTIVES: The study
      aimed at identifying factors affecting child development in Madinah, Saudi
      Arabia. DESIGN: A cross-sectional study with a multi-stage stratified random
      sample of children. SETTING: Well-baby clinics of the primary health care centers
      in urban and rural areas of the Madinah region, North-western Saudi Arabia.
      PARTICIPANTS: A sample of 1219 "normal" children below the age of six.
      INTERVENTION: Tools used for the study were the modified and translated Denver
      Revised-Pre-screening Developmental Questionnaire (R-PDQ), and the Denver
      Developmental Screening Test (DDST) kit together with a social questionnaire.
      Logistic Regression analysis was used to show any significant association(s)
      between the study variables and the 104 developmental items in the R-PDQ.
      RESULTS: Eight variables were found to be strongly associated with each of the
      developmental items. Mothers' education was found to be significantly associated
      with 21 developmental items. Number of children in the household was next to
      mothers' education in its association with child development. Place of residence
      and gender were found to be significantly associated with seven and one abilities
      respectively. CONCLUSION: Findings emphasized the importance of girls and
      mothers' education as an aid in stimulating the development of their children and
      enabling mothers to prepare children for school. Adequate birth interval, and
      prolonged breastfeeding are recommended to enable mothers to care for their
      children, communicate with them and foster sound development. Scrutinizing the
      child's home environment and involving parents in the developmental progress of
      their children are also considered important. More stimulation and educational
      play are recommended for rural children and male urban children.

PMID- 23008602
TI  - Predictive factors and incidence of complications in apparently healthy full term
      infants of diabetic mothers.
AB  - AIM: To determine the incidence of different complications of the apparently
      healthy full-term infants of diabetic mothers (IDMs) and whether these
      complications could be predicted early. METHODS: A prospective study was
      performed in the Nursery Unit of King Fahd Hospital of the University in Al
      Khobar over an 18-month period. Eligible neonates were those full-term IDMs who
      were asymptomatic at birth, with birth weight >= 2000 g and whose mothers had
      gestational or pregestational diabetes. AUDMs were routinely observed for at
      least 2 days. A complete blood count, glucose, bilirubin and calcium serum levels
      were monitored. The morbidity study group included all IDMs who experienced
      complications requiring treatment or observation for > 48 hours. RESULTS: One
      hundred and eighty eight infants with a birth-weight of 3411 +/- 616 g and with
      gestational age of 38.5 +/- 1.2 weeks were enrolled in the study. Asymptomatic
      hypoglycemia (31%) was mostly mild and transient. The rate of other complications
      such as hypocalcemia (4%), polycythemia (13%), hyperbilirubinemia (18%),
      intrauterine growth retardation (2%) with 30% rate for large gestational age.
      Using a logistic regression model; maternal insulin therapy, poor diabetic
      control, birth asphyxia, early neonatal hypoglycemia and polycythemia were found
      to be highly predictive of morbidity with an odd ratio of 2.41, 2.91, 9.65, 3.88
      and 3.74 respectively. CONCLUSION: Complications of apparently healthy IDMs
      appear to be very mild and transient. These were found to be strongly associated
      with specific perinatal events.

PMID- 23008603
TI  - Patterns of resistance to antibiotics at king fahd hospital of the university.
AB  - INTRODUCTION AND AIM: A sharp worldwide rise in bacterial resistance to
      antimicrobial agents in both nosocomial and community acquired pathogens has
      recently been observed. This may complicate treatment of infectious disease or
      increase the cost of its management. It is, therefore, important to regularly
      investigate the patterns of resistance to antimicrobial agents at both local and
      national levels. METHODS: The antibiograms of organisms isolated over a one-year
      period in King Fahd Hospital of the University were analyzed. RESULTS: Of the
      3679 microbial isolates of 35 types of organisms identified, the most common were
      Streptococcous spp (25.5%), S. aureus (16.1%), E. Coli (12.7%), Psueudomonas spp
      (9.3%) and Klebsiella spp (7%) High resistance rates (>50%) to ampicillin and to
      amoxycillin + clavulanate (AMX+CLV) were encountered in Enterobacter spp., and H.
      influenzae while in E. coli, the resistance was higher to ampicillin (60.0%) than
      to AMX+CLV (38.1%). With regard to S. aureus, 98.3%, 91.1% and 25.5% of isolates
      were resistant to penicillin, AMX+CLV and methicillin respectively but all were
      sensitive to vancomycin. High resistance (53% of 2830 isolates) to tetracycline
      was also observed especially in H. influenzae (80.5%), Streptococcous spp (72.9%)
      and E. Coli (54.5%). The same organisms were also highly resistant to
      trimethoprim/sulphamethoxazole with rates of 75.5%, 80.4% and 48.1% respectively.
      Moderate resistance (26% of 1567 isolates) to gentamicin was noted but the drug
      remained very effective against most tested gram-negative organisms. In addition,
      multiple resistance to gentamicin and AMX+CLV was also detected in 24.3% of 839
      isolates. CONCLUSIONS AND RECOMMENDATIONS: It is concluded that the alarmingly
      high pattern of bacterial resistance to antibiotics may reflect the extent of use
      of each antibiotic in the eastern province of Saudi Arabia. It is recommended
      that hospital antibiotic policies (purchasing, prescribing and dispensing) be
      based on, and regularly reviewed in accordance with hospital antibiogram results.
      A center for infectious disease control should also be established in each region
      of the Kingdom to disseminate information and coordinate antibiotic policies
      among hospitals.

PMID- 23008604
TI  - Knowledge, attitude and smoking patterns among nursing and laboratory technology
      students, dammam, saudi arabia.
AB  - OBJECTIVE: To study the reported practices of knowledge about and attitude
      towards smoking among nursing and medical laboratory technology (MLT) students,
      College of Medicine, King Faisal University at Dammam and Al-Khobar. SETTING:
      College of Medicine, Dammam and King Fahd Hospital of the University, Al-Khobar,
      Saudi Arabia METHODS: A cross-sectional approach involving a sample of 266
      students and interns (152 nursing and 114 MLT), which included all enrolled
      students in the academic year (1998/1999). A self-administered questionnaire was
      used to collect data covering knowledge, practice and attitude to smoking. SPSS
      was used for statistical analysis. RESULTS: The overall smoking prevalence was
      low (5.6%), slightly higher among nursing (6.6%) versus MLT (4.4%) students.
      Knowledge of and attitude towards smoking was generally satisfactory in both
      groups, although deficient in some key areas, such as the addictive nature of
      smoking, some of its consequences on health, and difficulty of quitting.
      CONCLUSION AND RECOMMENDATIONS: The prevalence of smoking among nursing and MLT
      students is generally low but their knowledge and attitude need improvement.
      Health education on facts, dangers and consequences of smoking should start as
      early as the primary school, and should continue throughout the education of
      future health professionals (role models for the community).

PMID- 23008605
TI  - Audit of diabetic care in a saudi primary care setting.
AB  - OBJECTIVE: To audit the care offered to diabetic patients attending the Family
      and Community Medicine Clinic (FAMCO), King Faisal University, Kingdom of Saudi
      Arabia (KSA). DESIGN: A cross-sectional study of medical records of 45 diabetic
      patients who regularly visited the clinic during a one-year period from June 1997
      to May 1998. SUBJECTS: Patients who presented at the clinic because of non
      insulin-dependent diabetes mellitus (type II). RESULTS AND CONCLUSIONS: The level
      of care for diabetic patients was relatively inappropriate, and some important
      parameters were under-recorded. Specific measures to improve and promote diabetic
      care in FAMCO clinics need to be undertaken. These include formulating and using
      protocols for diabetes management and better training of health-care providers.

PMID- 23008606
TI  - Attitudes of saudi media towards world health events.
AB  - INTRODUCTION: Mass media are very important in health education programmes.
      Health promoters rely on them to play a crucial role in their campaign. AIM: The
      aim of the study was to study the patterns of contribution of the Saudi daily
      newspapers on two international health occasion during the year 1416H (World AIDS
      Day 1995 and World Health Day 1996). MATERIAL AND METHODS: The study was
      retrospective, carried out by reviewing eight daily Saudi newspapers including
      all issues covering three months before and extending three weeks after each
      occasion. All newspaper materials concerning the two occasions were specified,
      and data obtained from them included types of materials, topics and
      characteristics of the paper. RESULTS: The study revealed that the newspapers
      gave more coverage to World AIDS Day than on World Health Day. This meant that
      journalists considered that AIDS was more interesting to the readers than the
      environmental topic of World Health Day. Most of the materials especially in
      World Health Day were published in the inner pages. These findings are in
      consonance with previous work, which showed that Saudi journalists had little
      interest in environmental issues. Nearly two thirds of the materials were news
      items about ministerial and activities of other organizations. Informative
      articles on health education and readers' participation were minimal. CONCLUSION:
      It was concluded that newspapers took not much interest on health matters
      especially health education.

PMID- 23008607
TI  - Development of health services in hajj seasons.

PMID- 23008608
TI  - Saudi medical education: challenges in the new millennium.
AB  - Medical education has been and continues to be a priority in the Kingdom of Saudi
      Arabia since the establishment of the first medical school more than 30 years
      ago. As the kingdom moves into the new millennium through its 100(th) birthday,
      several issues pertaining to medical education are noted. These include selection
      and admission criteria to medical schools, suitability concerns, and the need for
      reform of the current undergraduate curriculum as well as allocation and
      utilization of available resources. The postgraduate medical training programs,
      particularly the university-based, need re-evaluation, and definition of their
      future role in graduate medical education. Medical educators must make sure that
      research in medical education should not only survive but also thrive. In this
      article, some suggestions for Saudi medical education in n the new millennium are
      put forth.

PMID- 23008609
TI  - Pattern of surgical and medical diseases among pilgrims attending Al-noor
      hospital makkah.
AB  - OBJECTIVE: Hajj usually presents a unique medical crisis especially for the
      Emergency Department. This study will identify the surgical and medical cases
      that presented at the Emergency Department during Hajj and percentage admitted.
      DESIGN: A prospective study of the pattern of surgical and medical cases that
      presented at the Emergency Department of the largest tertiary care hospital in
      Makkah city and holy lands during Hajj. METHODS: The study was conducted
      prospectively during the 1413 (1993) Hajj pilgrimage from 20.11.1413 to
      20.12.1413. All Saudi and non-Saudi pilgrims presenting at the Emergency
      Department of Al-Noor Specialist Hospital were included. RESULTS: From the 7,676
      patients who came to the Emergency Department, 1426 were admitted. The commonest
      cause for surgical admission was trauma, while the commonest cause for medical
      admission was pneumonia. CONCLUSION: More than 50% of cases could have been dealt
      with in the Outpatient Department or Primary Health Care Centers.

PMID- 23008610
TI  - Obesity and associated risk of coronary artery disease among patients of primary
      health care centers in abha, saudi arabia.
AB  - OBJECTIVE: To estimate the magnitude of obesity and its relation to the 10 year
      probability of developing coronary artery disease (CAD) in patients attending
      primary health care centers (PHCCs) in Abha, southern Saudi Arabia. SUBJECTS AND
      METHODS: Saudi patients aged between 30-70 years who had attended three PHCCs in
      Abha city over a 6-month period (January to June 1998) and agreed to participate
      in the study were enrolled. All such patients had their weights and heights
      measured, body mass index (BMI) was calculated and they were screened for risk
      factors of CAD and requested to provide a fasting venous sample for lipoprotein
      analysis. The probability of developing coronary artery disease (PCAD) over the
      next ten years was calculated for each patient by means of the computer model
      based on Framingham heart study.2 RESULTS: A total of 858 subjects were studied:
      46% males and 54% females. The percentage of obesity was 49% and overweight 35%;
      Females were dominantly obese while overweight was more prevalent in males. Of
      the study subjects 11.5% were hypertensive with significantly higher BMI than
      normotensives (P=<0.001); diabetes mellitus was represented in 29.6% with no
      significant difference in their BMI from nondiabetics. Smokers were 4.2% and they
      had a significantly lower BMI than non-smokers. Individuals with high-risk
      threshold of TC/HDL-c ratio (>= 5.6% for women and >= 6.4% for men) represented
      70.48% and had significantly higher BMI than those with low risk threshold. There
      was no direct relationship between BMI and PCAD10 (r(2)=0.007, p<0.12).
      CONCLUSION: (1) Obesity is an epidemic health problem with an expected upward
      trend in Saudi Arabia similar to that of LISA and Western Europe. (2) The risk
      factors for CAD were highly prevalent among the PHCC patients and had a strong
      significant association with obesity; thus weight control should be an integral
      part of the prevention of CAD at PHCCs level. (3) Although obesity was found to
      have a significant individual association with CAD risk factors, obesity per se
      had no significant direct relationship with the probability of CAD at 10 years.
      This confirms the conclusion reached by NCEP 11 that obesity caused CAD through
      the associated risk factors.

PMID- 23008611
TI  - Effect of a breast cancer health education program on the awareness and practice
      of jeddah female secondary school students.
AB  - OBJECTIVE: To identify the effect of a school health education program on the
      knowledge of secondary school girls in Jeddah, Saudi Arabia, of breast cancer and
      breast self-examination (BSE) and their practice of BSE. METHODOLOGY: A pre
      tested, self-administered questionnaire was administered to secondary students
      before the commencement of the health education to assess their knowledge on
      breast cancer and their practice of BSE. The same questionnaire was handed 6
      months later to a smaller group of these students as a post-test. As the post
      test group was smaller than the pre-test group, an equal sample size from the pre
      test group was drawn for comparison. Random sampling and further analysis was
      done using the SPSS program, and for the comparison of the two groups, the
      student t-test and chi square were used. RESULTS: The post-test was answered by
      1372 students. The sampled re-test group comprised 1400 students (N= 7663)
      forming a sample of 18.3%. The ages for both groups ranged between 16-25 years
      (mean = 18.4; SD=1.9). Saudi nationals formed 73.4% of both groups and the
      proportion of married students was 8.4%. Those who reported that they had
      relatives with breast mass were 11.2%. The mean knowledge indexes on breast
      cancer reached 19.7 for the pre-test group and 43.0 for the post-group (t=31.2;
      p<0.0001). Correct answers for BSE rose significantly among the post-test group.
      A proportion of 27.2% students from the post-group reported that they had been
      motivated to practice BSE at least 3 times during the last 6 month. CONCLUSION
      AND RECOMMENDATION: The outcome of the school health education program on breast
      cancer had been successful in raising the awareness of secondary school girls and
      in helping them to practice BSE more. Hence, it is recommended that the programme
      be implemented in all female secondary schools and colleges.

PMID- 23008612
TI  - Epidemiology of brucellosis in Al medina region, saudi arabia.
AB  - OBJECTIVE: To evaluate the prevalence of brucellosis in the Al-Medina region of
      Saudi Arabia and to determine the related factors. METHOD: A cross-sectional
      survey was carried out in 1997 with a random multistage cluster sampling of 500
      households (4000 subjects). Tube Agglutination Test (TAT) and 2-mercapto-ethanol
      (2ME) analyzed blood samples. RESULT: The study revealed that the prevalence of
      brucellosis was 2.6%. The prevalence was shown to increase with age in rural
      communities and low socio-economic status. There are eight predisposing factors
      associated with brucellosis. These are the consumption of raw milk, and milk
      products, the keeping of livestock, milking of livestock, animal contact,
      butchering of raw meat, handling parturient animal and contact with placenta
      membrane. The overall prevalence of brucellosis among livestock as assessed by
      examining blood from a random sample of animals was estimated at 17.4%.
      CONCLUSION: THE FINDINGS OF THIS WORK INDICATE THAT: (1) There is high prevalence
      of brucellosis in the Al-Medina region of Saudi Arabia. (2) Very little is being
      done to prevent or minimize infections. (3) Control and prevention of brucellosis
      in animals and humans should be the goal in Saudi Arabia RECOMMENDATIONS: IT IS
      RECOMMENDED THAT: (1) the surveillance be strengthened; (2) there be strict
      adherence to hygienic practices on farms; (3) there be cooperation and joint
      supervision at the boundaries with neighboring countries; (4) there be health
      education.

PMID- 23008613
TI  - Factors affecting student motivation: perception of pre-clinical students in the
      college of medicine, king faisal university, dammam, saudi arabia.
AB  - OBJECTIVES: To study the relationship between student motivation for learning and
      38 factors related to teaching, curriculum and administration. METHOD: A total of
      231 male and female medical students in the first three pre-clinical years
      participated in the study by completing a questionnaire. RESULTS AND CONCLUSIONS:
      FACTORS THAT HAVE BEEN RATED AS STRONG PROMOTERS OF MOTIVATION INCLUDE: injecting
      relevant clinical information into lectures, encouraging student participation,
      revising previous lectures, using explanatory Arabic phrases, using the chalk
      board, providing specific course objectives, adopting one easy reference,
      concentrating on the core curriculum and showing respect to students. Factors
      that have been evaluated as inhibitors of motivation included: content overload,
      unscheduled quizzes, giving one quiz per subject in a semester, difficult exams
      and afternoon lectures.

PMID- 23008614
TI  - Stress in mothers of diabetic children in riyadh city, saudi arabia.
AB  - OBJECTIVES: The purpose of this study was to determine the presence of physical,
      social, financial and marital stress on mothers of diabetic children and the
      possible relationship of this stress to the epidemiological characteristics of
      the mothers. METHOD: It was a case-control study in which 125 mothers of diabetic
      children were selected randomly from 10 general and private hospitals in Riyadh
      city. A control companion group of 110 mothers who were free of chronic illness,
      was drawn from primary health care centers in the same city. Mothers in both
      groups were interviewed using a structured questionnaire. RESULTS: In the study
      group, 110 mothers were interviewed. Physical, social and financial stress was
      more common in mothers of diabetic children than in mothers in the control group.
      With the exception of marital stress, the differences were statistically
      significant. Physical stress was correlated positively with the frequency of
      blood tests and the working status of mothers. Social stress was correlated
      positively with the frequency of blood tests; but negatively with child's
      knowledge of diabetes mellitus. Financial stress was correlated positively with
      the presence of chronic illness but negatively with family income. CONCLUSION:
      Mothers of diabetic children are at risk of being under various kinds of stress.
      Certain epidemiological factors are associated with the development of the
      stress. These factors have to be taken into consideration in the management of
      the disease.

PMID- 23008615
TI  - Immediate discontinuation of intravenous fluids after common surgical procedures.
AB  - BACKGROUND: Intravenous (IV) fluids and nasogastric (MG) intubation can be
      discarded safely in some abdominal operations, but this practice seems rare in
      our community. SETTING: A University teaching hospital in Eastern Saudi Arabia.
      AIMS: To determine the feasibility of the practice in our setting and increase
      clinicians' awareness of it and encourage its general adoption. METHOD: A
      prospective verification study in consecutive ASA Classes I and II adult patients
      scheduled for four commonly performed operations. END POINTS: The practice was
      considered successful if the patient accepted early oral fluids and did not
      require re-insertion of IV line. RESULTS: The operations studied were
      appendicectomy (44), laparoscopic cholecystectomy (35), herniorrhaphy (19) and
      diagnostic laparoscopy (2). The patients' mean age was 34.1 years (range 14 to
      68); 60% were males. The overall success rate was 98%. Thus postoperative IV
      fluids proved to be unnecessary in these patients; cost savings were achieved and
      treating teams were freed to focus on other patients who truly required IV
      fluids. CONCLUSIONS: In our setting also, routine IV fluids are unnecessary and
      can be discarded safely after appendecectomy, cholecystectomy and herniorrhaphy
      in adults.

PMID- 23008616
TI  - Cough: a practical approach for the primary care physician in saudi arabia.
AB  - Cough is one of the cardinal symptoms of respiratory tract disorders and could be
      a manifestation of a serious non-respiratory tract disease. Cough is generated by
      an integrated mechanism between the central nervous and respiratory systems. The
      triggering factor of the above integration is an initial irritant, which
      stimulates the cough reflex and, hence, the mechanism of cough will take place.
      Persistent cough in a non-smoking adult is considered one of the most common
      presentations to physicians practicing in hospital or primary care settings and
      can be caused by many disorders. The objective of this article is to highlight a
      practical approach for the primary care physicians to the initial management of
      cough.

PMID- 23008617
TI  - Alternative medicine: which way forward?

PMID- 23008618
TI  - The pattern of alternative medicine use among patients attending health centres
      in a military community in riyadh.
AB  - BACKGROUND: Alternative Medicine (AM) is gaining popularity worldwide.
      OBJECTIVES: This study was conducted to determine the prevalence and pattern of
      AM use in a military sector of the Saudi community. METHODS: Three hundred and
      ten adult patients, visiting their family physicians over 6 weeks from the 1(st)
      of June 1998, were selected by systematic random sampling. They were asked to
      report worrying health problems and their use of modern medicine (MM) and AM.
      RESULTS: Forty-six percent of the patients had used AM before and about 19% had
      used it in the past 12 months. Alternative medicine practitioners were visited by
      16.5% of the study population. Herbal medicine users represented 8.7% of the
      study population, honey (4.5%), the black grain Nigella sative (3%) and cautery
      was used by one person only. Women, housewives and the illiterate were more
      likely to use AM. About 86% of all the study population preferred MM. The main
      source of information about AM was relatives (77%). A large proportion of
      patients who reported depression used AM (53%) or visited AM practitioners (33%).
      The average cost per visit to an AM pratitioner (166 Saudi Riyals) was higher
      than that in the USA ($27.60=100 Saudi Riyals). CONCLUSION: There is a need to
      educate the public through the media and health professionals on the appropriate
      use of AM; housewives and the illiterate should be targeted. A community-based
      household survey using interviewers not associated with the health system such as
      teachers (to avoid bias) is needed.

PMID- 23008619
TI  - Acceptance of premarital health counseling in riyadh city, 1417h.
AB  - BACKGROUND: Health counseling before marriage can be a most worthwhile and
      satisfying aspect of preventive medicine. It is important in genetic diagnosis
      and the prevention of hereditary, sexually transmitted and other infectious
      diseases. OBJECTIVES: To determine the acceptance of the concept of Premarital
      Health Counseling (PMHC), and to identify some factors, which may efect this
      acceptance among Saudis who attend Primary Health Care Center in Riyadh, Kingdom
      of Saudi Arabia (KSA), 1417H. METHODS: The present study is a cross-sectional one
      with a selected sample of Saudis who attended the Primary Health Care Centers in
      Riyadh during the year 1417H. A multistage sampling and equal allocation
      stratified sampling within was used to select 484 persons comprising an equal
      number of males and females, married and single above the age of 18 years. A pre
      designed pre-tested questionnaire sheet was used to collect the required data,
      which were then tabulated and statistically analyzed. RESULTS: The study
      indicated that 364 (75.2%) of the study population accepted the concept of
      Premarital Health Counseling. PMHC was positively affected by the advancing age,
      experience of marriage, educational level and well-understood Islamic-health
      related issues. Out f those who accepted the concept, 273 (75%) agreed on the
      exchange of PMHC certificates between couples to be married and 152 (42%) agreed
      on the implementation of legislation on PMHC. Also, 298 (82%) of them wanted PMHC
      to be confidential and 168 (46%) agreed to the concept despite its cost. As
      regards the location of PMHC, most of participants who agreed to PMHC would
      prefer it to be given at governmental establishments. RECOMMENDATIONS: The study
      recommended the implementation of PMHC in Saudi Arabia, since it was accepted by
      the study population. However, further studies should be carried out to determine
      the details to be incorporated in the PMHC, their implementation and legislation
      on demographic basis of the Saudi community. Also, a community health education
      program for PMHC has to be devised in collaboration with Islamic leaders.

PMID- 23008620
TI  - Non-fatal occupational injuries admitted to hospitals among general organization
      for social insurance workers in Al-khobar city, saudi arabia: experience of one
      year.
AB  - OBJECTIVES: (1) To determine the incidence rate of non-fatal occupational
      injuries requiring admission into private hospitals in Al-Khobar city during a 12
      month period among workers insured by the General Organization for Social
      Insurance (GOSI). (2) To describe the pattern, characteristics and outcome of
      these injuries. (3) To estimate their subsequent direct medical costs. METHODS:
      This is a cohort study design. The cohort consisted of workers at workplaces
      where insurance cover ensured admission into two private hospitals selected
      randomly in Al-Khobar city. A data-collecting sheet was used to collect the
      necessary data from both the patient and his medical file on admission into
      hospital. RESULTS: The injury incidence rate was 7.1 per 1,000 full-time workers.
      All injured workers were males. Grouped by nationality, 1.5% were Saudis, 74.8%
      from the Indian subcontinent and 13.2% Filipinos. Main injury sites included
      hands and fingers (32.1%) multiple parts (20.7%), lower limbs (20.5%), eyes, head
      and neck (11.5%) and back (9.5%). Falls were the main cause of injury (33.4%),
      followed by tools-related injuries (23.9%), falling objects (14.5%) and car
      accidents (12.0%). The majority of admissions (77.8%) were for periods less than
      1 week with only 7.1% for more than 3 weeks. Absence from work was more than 3
      weeks and less than 1 week in 35.5% and 24.9% of the admissions, respectively.
      The majority of the cases (65.0%) visited clinics 2-7 times. Direct medical cost
      per admission was less than SR 2,000 in 63.9% of the cases in one hospital (1 USD
      = SR 3.75). CONCLUSIONS: The incidence rate was lower than, but comparable to
      those rates estimated in more detailed surveys from other countries. Occupational
      injuries requiring admission into hospitals contributed to 18.3% of the total
      cases of injuries among insured people during year 1995 and were responsible for
      significant medical charges, human suffering and loss of productivity. Based on
      the results of this study, it is recommended that GOSI should study the reasons
      behind the current situation and find appropriate solutions.

PMID- 23008621
TI  - Views of primary health care trainees on their hospital training in internal
      medicine and pediatrics in saudi arabia.
AB  - OBJECTIVE: The aim of this study is to assess the perception and satisfaction of
      primary health care (PHC) trainees regarding their hospital training in Internal
      Medicine and Pediatrics. METHODOLOGY: A cross-sectional study was conducted by
      means of a self-administered questionnaire distributed to the trainees who had
      finished Medicine and/or Pediatrics rotation in 4 PHC training centers in Riyadh,
      Al-Khobar, Jeddah and Al-Medina during January 1996. RESULTS: Trainees were more
      satisfied with the Pediatric rotation than the Internal Medicine rotation.
      Significant relationship (p<0.05) was found between trainee satisfaction in
      Internal Medicine rotation and both the quality of training and the relevance of
      training to the needs of PHC trainees. On the other hand, in Pediatrics, the only
      variable which was related significantly to the trainees' satisfaction was the
      duration of the rotation, which was found to be sufficient (p<0.05). Trainees'
      dissatisfaction with the rotation was due to many factors, such as the imbalance
      between service work and educational sessions and the lack of awareness of other
      specialists about PHC as a career. CONCLUSION: Attention and effort should be
      directed towards the improvement of hospital training through a close
      collaboration between the decision-makers for PHC training and the hospital
      consultants. Also the needs of trainees should be taken into account during
      planning of hospital training.

PMID- 23008622
TI  - Psychiatric emergencies at a university teaching hospital in eastern saudi
      arabia.
AB  - BACKGROUND: This is a study of psychiatric presentations to an Accident and Emer
      gency (A & E) Department of a Saudi general teaching hospital. PATIENTS AND
      METHODS: Consecutive series of psychiatric presentations over 6 months to the A &
      E Department of a general teaching hospital at Al-Khobar, East-ern Saudi Arabia,
      were prospectively investigated. Diagnoses were made according to ICD-10
      Classification of Mental and Behavioral Disorders. RESULTS: There were 273
      visits, accounted for by 182 index subjects and 37 subjects who made 91 repeat
      visits (33.3%). The age range of the index group was 5 to 82 years, with 75%
      below 38 years of age. The majority of the index group (78%) and repeaters
      (97.3%) were Saudi. Most index subjects (52.7%) were married, but only 40.5% of
      repeaters were so. Family was the predominant source of referral of both index
      (53.8%) and repeat visits (60%). Mood disorders were the commonest diagno-ses at
      both index (31.7%) and repeat visits (39.6%). Most index subjects (57.7%) and
      repeated visits (56%) were managed at the A &E Department and given psychiatric
      outpatient appointment. Just over one-fifth (22%) of the index subjects and a
      little over a quarter (25.3%) of repeated visits were admitted to the psychiatric
      ward, Mood Disorders being predominant among both. CONCLUSION: Adequate
      psychiatric training of primary health care physicians and the establishment of
      crisis intervention community psychiatric services are advocated.

PMID- 23008623
TI  - Pattern of febrile illnesses in children seen at a pediatric ambulatory care
      setting.
AB  - BACKGROUND: Fever is the most common sign of childhood illnesses and febrile
      children constitute a substantial proportion of the practice of pediatrics and
      family medicine. OBJECTIVES: To highlight the pattern of febrile illnesses in
      children attending pediatric ambulatory health-care settings. METHODS: A one-year
      prospective study was conducted on febrile children who were consecutively seen
      and managed at two walk-in primary-care clinics in Sulaimania Children's
      Hospital, Riyadh. Data collection and analysis were structured around the
      principal study objectives. RESULTS: Among the 16,173 children seen, 4086 (25.3%)
      were identified as having a fever and evaluated to determine the aetiology of
      their febrile illness. Boys outnumbered girls and a significant increase in the
      frequency of febrile illnesses was noted in children 4 to 24 months of age. Upper
      respiratory tract infections were the commonest cause of fever (75%) and most of
      these infections were viral rhinopharyngitis. Viral gastroenteritis and pneumonia
      were prominent diagnoses, each accounting for 5% of febrile illnesses. Notably of
      low frequency were serious bacterial infections, such as meningitis (0.5%),
      cellulitis and bone or joint infection (1.8%) and urinary tract infection (0.7%).
      Only 9% of the febrile children required hospitalization. The ambulatory
      management of the other febrile children included the prescription of oral
      antibiotics to 64% of them. CONCLUSION: The proper clinical assessment of these
      febrile children and the prudent use of laboratory tests and antimicrobials
      remain the most important management strategies in primary health-care practice.

PMID- 23008624
TI  - Malignant melanoma of the skin: a case report from the eastern region (dammam
      central hospital), saudi arabia and epidemiological review.
AB  - Worldwide malignant melanoma is the commonest tumor of the skin, though it occurs
      in many other organs. It is a serious disease, the prognosis of which is poor if
      not detected and treated early. The disease is on the increase in many countries
      e.g. USA,1 England and Wales,2 Australia,3 and many parts of the world.4-6 Saudi
      Arabia is a vast country which is undergoing rapid development with a changing
      social and economic environment. To the best of our knowledge, not many studies
      or reports of malignant melanoma have issued from the Eastern Region. It is
      therefore, important to report this case and review the incidence of the disease.

PMID- 23008625
TI  - Tips from the editor.

PMID- 23008626
TI  - Rift valley Fever: lessons to be learned.

PMID- 23008627
TI  - Hypertension in diabetics registered in primary health care centers in makkah
      district, saudi arabia.
AB  - BACKGROUND: Hypertension in diabetes is a common and important problem, which
      aggravates diabetic macro- and microvascular complications. Since both diabetes
      and hypertension are common diseases, their follow up in primary health care
      centers should emphasize the early detection of hypertension in diabetes. This
      study aims at studying the magnitude of hypertension in diabetic subjects
      registered in primary health care centers. METHODS: A sample of 1039 diabetic
      subjects registered at the primary health care in urban and rural Makkah region
      were interviewed. Information gathered included demographic and diabetes-related
      variables. Blood pressure and body mass index were determined for 1020 subjects.
      RESULTS: Diabetic subjects who had high blood pressure readings amounted to 560
      (54.9%), of whom with stage 1, 2, and 3 hypertension formed 25.5%, 7.0% and 2.5%,
      respectively. Subjects with undetected high blood pressure amounted to 225
      (22.1%). There was significant association of high blood pressure with age, male
      gender, body mass index and low education. CONCLUSION: The problem of
      hypertension in diabetes could be sizeable. Many patients may remain undetected.
      A diligent search for diabetic subjects with elevated blood pressure should be
      made through an efficient system of follow up in the PHCC centers.

PMID- 23008628
TI  - Adolescents and cancer: a survey of knowledge and attitudes about cancer in
      eastern province of saudi arabia.
AB  - OBJECTIVE: To determine the knowledge and attitudes of adolescents in the Eastern
      Province of Saudi Arabia towards cancer. METHODOLOGY: A pre-structured tested and
      revised questionnaire was administered to a randomly selected sample from four
      high schools (two males and two females) in Dhahran, Saudi Arabia. RESULTS: Data
      were obtained from 572 adolescents. There was a marked variability in knowledge
      across informational items, particularly about the possible causes and how to
      avoid developing cancer. CONCLUSION: Students possess some knowledge of cancer,
      although this knowledge was not uniform. There were misconceptions about cancer
      and its pervention. The researcher concludes that the development and
      implementation of school health education programs on cancer are needed in this
      population.

PMID- 23008629
TI  - Inpatients satisfaction with nursing services at king khalid university hospital,
      riyadh, saudi arabia.
AB  - Recent development and changes in health care services in Saudi Arabia have
      encouraged a search a search for comprehensive and established measurements of
      the quality of care. Patient satisfaction with nursing care in particular has
      ferquently been used as a sensitive and objective measure of quality of hosiptal
      services. OBJECTIVES: THE OBJECTIVES OF THIS STUDY ARE: (1) to assess the level
      of inpatient satisfaction with nursing care (PSWC) in the various wards of the
      hospital; (2) to assess the socio-demographic determinants of PSWC in addition to
      the effects of duration of hospital stay and type of wards on the level of
      satisfaction. METHODS: The sample consisted of randomly selected 450 inpatients
      with probability proportion to the size of the wards. The data was collected by
      personal interviews using a 21-item structured questionnaire pertaining to
      nursing services. RESULTS: The results revealed that the instrument of
      measurement was valid and reliable. The overall mean satisfaction score was 2.4
      (77%) and the highest mean satisfaction was for items on skillfulness and the
      lowest score was for communication items. Multiple regression analysis indicated
      that sex, age, marital status and duration of stay are the most imortant
      predictors of PSWC; female, young, married and short duration of hospital stay
      have the highest satisfaction score. CONCLUSION: In conclusion, this study has
      highlighted the aspects of nursing care at King Khalid University Hospital (KKUH)
      which need re-examination by the management. The most importance findings have
      been that there is: (1) a shortage of nurses at the hospital; (2) limited
      communication between nurses and patients: most probably due to cultural and
      language barriers; (3) no proper oversight of patients personal hygiene; (4)
      dissatisfaction of male patients with most of the nursing care rendered. These
      results offer the hospial management the opportunity to work out stategies to
      connect the deficiencies highlighted.

PMID- 23008630
TI  - Continuing medical education on infectious diseases: a saudi university hospital
      experience.
AB  - BACKGROUND: Continuing medical education (CME) is an important and useful
      activity for updating knowledge in order to improve for outcome of health care. A
      CME update symposium on Infectious Diseases was therefore organized at the King
      Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia. Participants
      included clinicians, laboratory personnel and nursing staff from different
      hospitals and universities in Saudi Arabia. OBJECTIVES: To report the proceedings
      of the first CME on Infectious Diseases in the region and to evaluate it using a
      questionnaire-based feedback. METHODOLOGY: This CME was evaluated on specific
      feedback obtained on standardized evaluation forms provided during the symposium.
      The responses of 194 participants were statistically analyzed for the various
      components of the symposium. RESULTS AND CONCLUSION: Salient important issues
      covered during the program are presented. The CME included five sessions on:
      hospital acquired infections, immunology, mycotic diseases, malaria,
      lesihmaniasis and virology. Some lacunae were also identified. The evaluation of
      the scientific sessions showed a satisfaction level of 3.98 +/- 0.59, on a scale
      of five. As this CME activity proved successful on many counts, it was concluded
      that it was worthwhile to conduct updates on infectious diseases on a regular
      basis.

PMID- 23008631
TI  - Hydatidiform mole: a study of 90 cases.
AB  - OBJECTIVES: To determine the incidence, epidemiology, complications and
      management of Hydatidiform mole (HM) at the King Fahd Hospital of the University
      (KFHU), Al-Khobar, Saudi Arabia. METHODS: A retrospective study was conducted
      covering a period of 15 years from May 1983 to May 1998. There were 90 cases of
      hydatidiform mole. The details of maternal characteristics, clinical
      presentation, tumor behavior, management and complication were studied. RESULTS:
      There were 40,700 deliveries during the study period giving an incidence of
      hydatidiform mole (HM) of 2.2/1000 deliveries. The most common clinical feature
      was vaginal bleeding which was noted in 81 (90%) cases. Fifty-six (62%) cases had
      uterus larger than dates, while in 12 (13%) cases, the uterine size was smaller
      than dates. Ovarian enlargement was noted in 24 (27%) cases. Complications in the
      form of hemorrhage occurred in 19 (21%) cases and 9 (10%) cases were complicated
      by cated by sepsis. The complications were more common in patients presenting
      late to the hospital. There were 6 (6.7%) cases of invasive mole and 3 (3.3%)
      cases of choriocarcinoma during the follow-ups of the study group. CONCLUSION: On
      the basis of this study, the incidence of hydatidiform mole is comparable to the
      incidence in some oriental countries. Earlier diagnosis and treatment of HM will
      probably result in the decrease of complications found in this study.

PMID- 23008632
TI  - Issues in peak expiratory flow rate measurements: analysis and interpretation of
      results.

PMID- 23008633
TI  - Evidence-based medicine: conceptualization unto application.

PMID- 23008634
TI  - The frequency of health-related behaviors among saudi adolescents visiting
      primary health care centers in riyadh city.
AB  - BACKGROUND: The primary aim of the study was to calculate the prevalence of some
      of the health risk associated behavior like insufficient amount of exercise,
      cigarette smoking, alcohol intake, illicit drug use, driving below age of 18, and
      illegal sexual practices among the Saudi adolescents in Riyadh city. The second
      was to study the association between cigarette smoking and the above behaviors.
      MATERIAL AND METHODS: It was a cross-sectional survey with 1473 Saudi
      adolescents, 852 males (57.8%) and 621 females (42.2%) aged 11 to 21 years
      attending the selected 10 Primary Health Care Centers (PHCCs) were invited to
      complete a 23-item questionnaire. Part of the questionnaire was used to measure
      the frequency of some adolescent behavior. These questionnaires were collected
      within a period of one month from 15 May to 15 June 1998. The PHCCs were selected
      randomly in Riyadh city. RESULTS: The prevalence of cigarette smoking was 12.7%,
      males smoking more than females (19.0% vs. 4.0%); male smokers exercised
      significantly less than nonsmokers (p<0.025). Only 4.5% of the sample reported
      alcohol use, 6.4% reported illicit drug use, and 8.0% reported illegal sexual
      practice. There is a statistically significant association between smoking and
      other risk behavior. It was found that 41.1% of males below the age of 18 drive a
      car, and 45.1% of the study sample that drive had a car accident. CONCLUSIONS:
      The prevalence of illicit drug use, alcohol intake, and illegal sex in Riyadh
      city is much less than in the west. Cigarette smoking is an antecedent to more
      negative behavior. Antismoking programs including the prevention of the sale and
      use of cigarettes in public places are needed to decrease its prevalence. The
      application of firm traffic laws is also essential.

PMID- 23008635
TI  - Quality of health education posters in primary health care centers in Al-khobar
      town, eastern province.
AB  - BACKGROUND: Health Education (HE) is vital to each of the seven other central ele
      ments of Public Health Care (PHC). HE must be carefully planned and implemented.
      A crucial part of HE is planning, production and placement of effective HE
      posters. OBJECTIVE: Assess the quality of health education posters in Al-Khobar
      PHC centers. METHODS: A cross-sectional study of a sample of 138 HE posters in
      three PHC centers in Al-Khobar was conducted. The quality of posters in relation
      to set criteria was measured using a data sheet and scoring system developed by
      the investigator. RESULTS: The health education subjects displayed were among the
      common health problems in Saudi Arabia in 134 (97.1 %) of the posters.More than
      one-third (34.8%) had been displayed for more than one year. In 74 (53.6%) of the
      posters, the source of scientific information was unknown. The assessment showed
      that 109 (79%) posters were of optimal quality. CONCLUSION: The study showed that
      the health education posters in PHC centers in Al-Khobar were relatively
      satisfactory, though they did not fulfill some of the required criteria. Health
      education posters should be included in the assessment of health education
      programs in primary health care centers.

PMID- 23008636
TI  - Risk factors of bronchial asthma in bahrah, saudi arabia.
AB  - BACKGROUND: Asthma is a common health problem whose prevalence in Saudi Arabia
      has risen over the last few decades. Brick factories in the city of Bahrah have
      exacerbated the problem, and increasing numbers of asthma cases are attending
      local primary health care centers. OBJECTIVE: Determine the risk factors of
      asthma in Bahrah. MATERIALS AND METHODS: The study was comprised of 110 cases of
      bronchial asthma resident in Bahrah who were diagnosed by the treating physicians
      and 110 healthy controls matched in age and sex. A questionnaire was completed
      from cases and controls, consisting of data regarding personal, familial, indoor
      and outdoor environmental factors that may be potential risk factors to asthma.
      Bivariate and multivariate logistic regression analyses were done to assess risk
      factors. RESULTS: The mean ages of cases and controls were 22.4 (+/- 16.7) and
      22.8 (+/- 16.1) years, respectively. Each group consisted of 64 males (58%) and
      46 (42%) females. There was a significant association between distance from
      houses to brick factories and bronchial asthma (Chi square for linear trend =
      26.6, p<0.001). Multivariate logistic regression analysis showed that living
      within one kilometer of a brick factory (OR=5.1, CI=2.33-11.16), family history
      (OR=4.6, CI=2.16-9.78), allergic rhinitis (OR=3.39, CI=1.49-7.69), skin atopy
      (OR=4.6, CI=1.53-13.87) and recurrent respiratory tract infections (OR=4.1,
      CI=1.79-9.22) were independent risk factors for asthma in Bahrah. CONCLUSIONS AND
      RECOMMENDATIONS: Brick factories, family history and history of rhinitis, skin
      atopy, or recurrent respiratory tract infections are risk factors of bronchial
      asthma. An in-depth study to asses air pollution in Bahrah is recom-mended.
      People are advised not to live near brick factories.

PMID- 23008637
TI  - Cost of the drugs dispensed from primary health care centers for summer visitors
      to aseer region.
AB  - OBJECTIVES: Recognize the patterns and the cost of the drugs dispensed to summer
      visitors who attended Primary Health Care Centers (PHCCs) in Aseer region.
      METHODS: This study was conducted in Aseer region during the summer of 1998. The
      investigators designed and distributed special forms on which were blanks for
      names, age, sex, diagnosis and drugs that were prescribed for summer visitors who
      attended PHCCs in Aseer region. At the end of season, all the forms were
      collected and analyzed manually by well-trained nurses and assistant pharmacists.
      The cost of the drugs was calculated according to the price list provided by the
      Medical Supply Department. RESULTS: A total of 96327 forms were evaluated. These
      represented 25% of the total number of prescriptions issued by PHCC physicians
      during the summer season. The total cost of the dispensed drugs was estimated as
      190533 SR (50808$). About 20% of what was dispensed was for summer visitors who
      had utilized the PHCC services in Aseer region. Antibiotics and painkillers cost
      42% and 21% of the total cost respectively. CONCLUSION: This study showed that
      the cost of drugs for summer visitors in Aseer region was 20.5% of the total drug
      cost. This additional cost should be considered in planning the drug budget.

PMID- 23008638
TI  - Sero-prevalence of toxoplasmosis in pregnant mothers and new born infants in
      eastern province, saudi arabia.
AB  - BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoa of worldwide
      distribution. In immunocompetent adults, it is usually the cause of asymptomatic
      infection. However, infection during pregnancy poses a special risk because of
      the teratogenic effect of toxoplasma. OBJECTIVE: Determine the sero-prevalence of
      toxoplasmosis in pregnant women and newborn infants in King Fahd Hospital of the
      University, Al-Khobar, Eastern Province. METHODS: In this hospital-based study,
      sera from 175 pregnant females were screened for toxoplasma IgG and IgM. RESULTS
      AND CONCLUSION: A very low number (N=1/175, 0.57%) of pregnant mothers
      seroconverted during pregnancy, although many (N=69/175, 39.4%) were recorded
      with inactive toxoplasmosis during pregnancy. Delivery was normal in all cases
      except for a small number (N=1/175, 0.57%) of newborns (as recorded from cord
      blood) who were positive for toxoplasmosis.

PMID- 23008639
TI  - Primary health care ... the way forward: everyone responsibility, everyone
      business.

PMID- 23008640
TI  - Correlates of various presentation modes of acute otitis media in saudi children.
AB  - PURPOSE: To describe correlates of various modes of presentation and identify
      some surrogates of poor outcome of children less than 5 years with Acute Otitis
      Media (AOM). PATIENTS AND METHODS: This is a cross-sectional survey conducted at
      11 primary health care centers in Riyadh city over 3 month period. A total of 140
      children, each less than 5 years of age and presenting with a new episode of AOM
      were enrolled. Twenty-eight family physicians participated in the study. Each
      physician made the diagnosis of AOM based on history and clinical examination of
      the tympanic membranes (TM) using an otosocope. Poor outcome was defined as
      children presenting with otorrhea. RESULTS: The majority of children presented
      with fever (62%), URTI (58%) and earache (54%). Presence of URTI, irritability,
      or sleeplessness were positively associated with redness and dullness of TM
      (p<0.05). Thumb sucking reduced the risk of bulging (OR = 0.29, 95% CI: 0.07
      0.94). Children of illiterate fathers were more likely to present with otorrhea
      (X(2) = 4.66, p< 0.05). Bottle feeding increased the risk of otorrhea by two fold
      (OR = 2.26, 95% CI:1.01-5.05). CONCLUSION: Children with AOM presenting as URTI,
      irritability or sleeplessness will showed redness and dullness of the TM as
      clinical signs of the disease. Thumb sucking was found to be protective from
      bulging of the TM. Having an illiterate father and being bottle fed were found to
      be surrogates of otorrhea .

PMID- 23008641
TI  - School boys with bronchial asthma in Al-khobar city, saudi arabia: are they at
      increased risk of school absenteeism?
AB  - OBJECTIVE: The objective of this cross-sectional study was to determine the mean
      period of school absenteeism (MPSA) among Questionnaire Diagnosed Asthmatic (QDA)
      Saudi schoolboys of Al-Khobar city and the factors associated with it. METHODS:
      The methodology of this cross-sectional study included the distribution of a self
      administered questionnaire, which was completed by the parents of 1482 schoolboys
      who satisfied the selection criteria of the study. RESULTS: The prevalence rate
      of QDA was 9.5% (141/1482). MPSA among Questionnaire Diagnosed Asthmatic Boys
      (QDAs) was 13.6 +/- 3.4 days compared to 3.7 +/- 2.2 days among non-QDA boys (non
      QDAs). Among QDAs, it was associated significantly and positively with those who
      were younger, with a decreasing level of socioeconomic class, history of pets at
      home, presence of a current smoker in the family (father or both parents), visit
      to a hospital emergency room, and admission to hospital. It was significantly and
      negatively associated with concomitant use of prophylactic medication(s),
      including those used appropriately. QDAs from middle and lower socioeconomic
      classes used less prophylactic medication(s) but had had more visits to an
      emergency room and had admissions to hospital. The multiple linear regression
      equation for the total period of school absenteeism (TPSA) during the current
      academic year was generated. CONCLUSIONS: QDAs have higher MPSA compared to their
      non-asthmatic classmates. The impact of this disease increases particularly among
      QDAs belonging to lower socioeconomic families.

PMID- 23008642
TI  - A non-comparative descriptive study of the risk factors for childhood disability,
      and the rehabilitation services in jeddah, saudi arabia.
AB  - OBJECTIVES: Identify the possible risk factors in our community that may
      influence having a disabled child, and identify the rehabilitation services
      available to disabled children. METHODS: Data were collected from six
      rehabilitation institutes for auditory, visual and mental disabilities in Jeddah
      City during April 1999. Complete data available on sociodemographic and medical
      risk factors were extracted from the institutes' files. Personal interviews with
      the disabled were conducted to confirm information on the services offered to
      them. RESULTS: Certain modifiable risk factors affecting child health, such as
      early and late marriages and childbearing, illiteracy, unemployment, high parity
      and consanguineous marriages still exist in our community. Occupational hazards
      were also detected among military workers and working women. Disabilities related
      to perinatal health with antenatal, natal and postnatal components were also
      observed. According to resources available, various rehabilitation services are
      offered to disabled children. CONCLUSION: The need for intervention in two areas
      of health is crucial. The first is the prevention of future disabilities through
      continuous research, modification of unfavorable habits and the strengthening of
      the quality of perinatal care. The second is the improvement of rehabilitation
      services in order to raise the quality of life of the handicapped.

PMID- 23008643
TI  - Acute abdominal pain in women of child-bearing age remains a diagnostic dilemma.
AB  - Abdominal pain is perhaps the most challenging of all the presenting complaints
      in the emergency department. It is estimated that it accounts for 5%-10% of all
      visits. Causes of abdominal pain range from the inconsequential to the life
      threatening. In addition, it nearly always poses a greater degree of diagnostic
      uncertainty in women of child-bearing age as compared to males. Such difficulties
      become more pronounced in pregnant women where the unwritten policy seems to be:
      If she is pregnant blame the pregnancy. This policy is justified by the favorable
      clinical outcomes. However, in a small but significant number of patients, this
      policy has the potential of creating delays and increasing the risk of
      unwarranted complications. Delays in management may lead to emotional trauma,
      loss to the society, and the potential for serious liability.This review was
      undertaken at King Fahd hospital of the University, Eastern Province of Saudi
      Arabia, with a literature search covering a period of over twenty years. It
      mainly highlights the diagnostic difficulties in young women presenting with
      acute onset abdominal pain, and possible solutions.It also suggests a policy
      which includes a careful clinical approach with liberal consults between the
      surgeon and the gynecologist reinforced by a judicious use of the available
      diagnostic aids leading to potentially favorable outcomes.

PMID- 23008644
TI  - The internet and the world wide web: applications for family physicians in saudi
      arabia.
AB  - The introduction of the World Wide Web has revolutionized the applications of the
      computer and the Internet in the medical field. The Web provides an easy and cost
      effective way of retrieving medical information and a more flexible way of
      communicating with patients and colleagues. Family practice is a specialty in
      which care is given to persons as individuals and members of families regardless
      of their age, gender or specific problems. To provide quality family practice, a
      family physician should be a good communicator, a critical thinker, a resource
      and information manager, a life-long learner, a care giver and a community
      advocate. Providing such high quality care requires that family practice be an
      information-sensitive specialty. However, the expansion of the new electronic
      resources on the Internet and the Web poses a real challenge to the family
      physician. Family physician in Saudi Arabia need to have basic skills and
      knowledge for easily retrieving and finding reliable Internet information for his
      professional development and the care of his patients. This article addresses the
      Web applications for family physicians in Saudi Arabia, giving examples of the
      most important Websites.

PMID- 23008645
TI  - Sildenafil (viagra) and the heart.
AB  - Sildenafil (Viagra) is the most effective oral therapy currently available for
      erectile dysfunction. Patients should be given clear instructions regarding the
      use of sildenafil. The most common side effects include flushing, headaches,
      dyspepsia, and transient visual changes. In combination with nitrates, it can and
      has caused fatal hypotension. It should not be prescribed to patients on
      nitrates. Additionally, nitrates should not be administered to anyone who has
      recently ingested sildenafil. Synergetic blood pressure lowering has not been
      observed when sildenafil was used with other classes of antihypertensives.
      Sildenafil is not offered to patients with low cardiac output states, those on
      intensive regimens to prevent heart failure or those with acute coronary
      ischemia.

PMID- 23008646
TI  - Medical education: which way forward?

PMID- 23008647
TI  - Health care services in saudi arabia: past, present and future.
AB  - Health services in Saudi Arabia have developed enormously over the last two
      decades, as evidenced by the availability of health facilities throughout all
      parts of the vast Kingdom. The Saudi Ministry of Health (MOH) provides over 60%
      of these services while the rest are shared among other government agencies and
      the private sector. A series of development plans in Saudi Arabia have
      established the infra-structure for the expansion of curative services all over
      the country. Rapid development in medical education and the training of future
      Saudi health manpower have also taken place. Future challenges facing the Saudi
      health system are to be addressed in order to achieve the ambitious goals set by
      the most recent health development plan. These include the optimum utilization of
      current health resources with competent health managerial skills, the search for
      alternative means of financing these services, the maintenance of a balance
      between curative and preventive services, the expansion of training Saudi health
      manpower to meet the increasing demand, and the implementation of a comprehensive
      primary health care program.

PMID- 23008648
TI  - Induced abortion from an islamic perspective: is it criminal or just elective?
AB  - BACKGROUND: Induced Abortion for social reasons is spreading all over the world.
      It is estimated that globally 50 million unborn babies are killed annually,
      resulting in the deaths of 200,000 pregnant women and the suffering of millions.
      The complications of illegal abortion are very serious. Abortion is still used in
      many countries as a means of family planning. The medical reasons for abortion
      are limited and con-sti-tute a small proportion of all abortion cases. This paper
      discusses the different views on abortion, its history, its evolution over time,
      and the present legal circumstances. The emphasis is on the situation in Islamic
      countries and the effect of Islamic Fatwas on abortion.

PMID- 23008649
TI  - Attitude, practice and needs for continuing medical education among primary
      health care doctors in asir region.
AB  - OBJECTIVES: Assess the attitude and practice of Primary Health Care (PHC)
      physicians in Aseer region, their educational needs and recommendations to
      establish a continuing medical education program (CMEP) to address these needs.
      METHODS: This study was carried out during the first half of 1999 in Aseer
      region, Saudi Arabia. A self-administered questionnaire was distributed to all
      PHC physicians in Aseer region. The questionnaire explored socio-demographic
      characteristics, scientific background, the attitude towards CME, the current
      method for medical updating, the barriers to CME, and the topics requested for a
      future CMEP. RESULTS: There were a total of 383 PHC physicians in Aseer region,
      86% of whom responded to this questionnaire. Of these 76.1% were Arabs, 91.2%
      were married, 26.3% had post-graduate qualifications and 68.6% had had no
      experience in the PHC field prior to arriving in Saudi Arabia. Most respondents
      showed a positive attitude toward CME. Nearly two-thirds (64.4%) had adequate
      time for CME, 86.7% allocated time for CME, and 64.4% were ready to participate
      as tutors in CMEP. Suggestions were given by 49.6% for establishing a CMEP in the
      region. The most popular methods practiced for CME were reading medical journals
      (79.8%) and medical textbooks (53.8%), and attending training courses (39.6%).
      The medical subjects that were identified as needed were emergency medicine
      (24.5%), pediatrics (20.8%), internal medicine (20%), and obstetrics/ gynecology
      (18.7%). However, 75.2% also indicated that computer literacy was a practice
      requirement, 57.7 and 54.1% thought designing diabetes and hypertension
      management programs were vital, and 41.7% said learning how to design a PHCC
      action plan was essential. CONCLUSION: PHC physicians in Aseer region had a
      positive attitude towards selective CMEP. They needed CMEP but felt its content
      should be in line with their practice needs.

PMID- 23008650
TI  - Continuing pharmaceutical education for community pharmacists in the eastern
      province of saudi arabia.
AB  - BACKGROUND: Community pharmacists in Saudi Arabia very often make decisions that
      affect patient outcome. Previous studies have indicated that they have access to
      limited sources of information. Therefore, structured continuing pharmaceutical
      education (CPE) is necessary to improve their standards and attitudes. AIMS:
      Identify the most important topics for CPE as well as the most significant
      barriers to conducting CPE successfully. METHODS: A questionnaire was distributed
      to 120 pharmacists working in 88 community pharmacies in the Eastern Province of
      Saudi Arabia. The survey contained five sections: general background, topics for
      CPE that could be of great interest to community pharmacists, possible obstacles
      to attending CPE, method of instruction, and the most suitable time and day of
      the week for conducting CPE. RESULTS: One hundred and five (87.5%) pharmacists
      answered the survey questionnaire. The rank order of the five most selected
      topics for CPE were: drug interaction (81.9%), drug use during pregnancy (77.1%),
      use of anti-microbial agents (62.5%), pharmaceutical ethics (53.3%), geriatric
      and pediatric pharmacology (45.7%). For pharmacists, the most important obstacles
      to attending CPE were lack of time (96.2%), distance from practice (74.2%), and
      lack of programs or information about these programs (54.3%). Interestingly,
      47.6% of the pharmacists recommended credentialing CPE and stated that knowing
      the lecturer was not considered an important factor. CONCLUSION AND
      RECOMMENDATIONS: The findings of this study demonstrated that pharmacists are
      willing to participate in CPE programs. However, the working conditions of
      pharmacists would be a major barrier to their attendance. Therefore, improvement
      of the working conditions of community pharmacists, development of credited CPE
      programs in each region, as well as improving communication between the Saudi
      Pharmaceutical Association and community pharmacists are highly recommended.

PMID- 23008651
TI  - SEROPREVALENCE OF RIFT VALLEY FEVER AMONG SLAUGHTERHOUSE PERSONNEL IN MAKKAH
      DURING HAJJ 1419h (1999).
AB  - OBJECTIVES: Determine the sero-prevalence of rift valley fever (RVF) among
      slaughterhouse personnel in Makkah during Hajj and define personal and work place
      correlates. MATERIALS AND METHODS: A sample of 294 participants were chosen
      randomly from slaughterhouse personnel in Makkah during Hajj 1419 (1999). Data
      were collected through personal interviews using a pre-designed questionnaire
      consisting of personal and work place variables, e.g. age, nationality, type and
      hours of work. A blood sample was collected from each participant and tested by
      enzyme immuno-assay for IgG antibody using killed antigen for rift valley virus.
      RESULTS: Of the total sample, 17% was seropositive for RVF. The rate of infection
      varied with country of origin: Syria (10.6%), Egypt (21.2%), Bangladesh (22.6%),
      Mali (47.1%) and Niger (50%). The number of animals slaughtered per hour and
      daily hours of work were significantly associated with prevalence of RVF
      (p<0.05).Multivariate logistic regression analysis showed that nationality and
      daily hours of work predicted 84.1% of the occurrence of RVF. RECOMMENDATIONS:
      Sero-surveys should be done among slaughterhouse personnel in Saudi Arabia and
      other countries particularly in countries known to be free from RVF, e.g. Syria
      and Bangladesh to assess the situation of RVF. The importation of animals from
      endemic areas should be banned.

PMID- 23008652
TI  - Patients' satisfaction with primary health care centers services in kuwait city,
      kuwait.
AB  - BACKGROUND: Assessment of patient satisfaction offers a way of optimizing health
      status and prevents waste of medical resources. The direct measurement of patient
      satisfaction is a new phenomenon in Kuwait. OBJECTIVE: Assess patient
      satisfaction with respect to primary health care services and study any patterns
      of association of sociodemographic variables on the patient satisfaction level.
      METHODS: The sample consisted of 301 patients selected systematically from five
      primary health care centers to represent various geographic areas in Kuwait City.
      Just over 56% of the sample were females, 59% were married, the great majority
      (70.4%) were government employees, more than 60% had a monthly income of less
      than 900 KD, more than 54% were intermediate and high secondary school graduates,
      and 37% were university graduates or had advanced degrees. The data was collected
      by personal interview using structured questionnaire. RESULTS: The overall mean
      satisfaction was 3.1 points out of five (62%). The mean satisfaction scores were
      3.64, 3.29, 3.08, 3.05, 2.21 for laboratory, pharmacy, radiology, dental and
      physician services, respectively. The highest mean score for physician services
      was obtained for communication skills (2.23); for pharmacy services, the
      availability of medicine (4.01); for laboratory services, the availability of lab
      materials (3.73); for radiology services, the waiting time for x-ray (3.60); and
      for dental services, the adequacy of dentists (3.27). The results indicated that
      gender, income, marital status and occupation were the most consistent
      demographic predictors of satisfaction, with females, those with lower income,
      lower education levels and the unemployed having higher mean satisfaction scores.
      CONCLUSION: There is a need for corrective intervention in some service areas and
      for an educational program to inform patients of the objectives and limitations
      of primary health services.

PMID- 23008653
TI  - Pattern of intestinal parasitic infection among food handlers in riyadh, saudi
      arabia.
AB  - OBJECTIVE: Identify the types and prevalence of intestinal parasites among food
      handlers, and test the effectiveness of the current pre-employment screening
      policy. METHODS: A cross sectional survey was carried out in the catchment areas
      of seven primary health care centres (PHCCs) to represent various sections of
      Riyadh city. A total of 700 food handlers working in restaurants were randomly
      selected from the study area. All study subjects were asked to complete a data
      collection form and to bring a fresh stool specimen on the specified day to the
      designated PHCC. RESULTS: About 66% of the selected subjects complied in bringing
      fresh stool specimens. Fifty nine (12.8%) of the specimens were positive for
      parasites. There was a significant association between the food handler's
      nationality and the likelihood of a positive specimen result, being highest among
      the Bangladeshis (20.2%) and Indians (18.5%) and the lowest among the Arabs
      (3.4%) and the Turks (10%). The commonest intestinal parasites isolated were
      Giardia lamblia (33.8%), followed by Enterobius vermicularis (27.4%). The current
      screening policy does not seem effective, as there was an absence of significant
      association between holding a valid PEHC and the test result, with 81% of the
      positive results from persons holding valid pre-employment health certificates
      (PEHCs). CONCLUSIONS: Though it is obligatory for food handlers to hold a PEHC in
      Saudi Arabia, the prevalence of intestinal parasites remains high. Possible
      solutions include health education on hygiene, more frequent stool tests, and
      assessment of the current annual screening procedure.

PMID- 23008654
TI  - Knowledge and attitude towards screening mammography among 400 women in the
      eastern province of saudi arabia.
AB  - OBJECTIVE: Assess knowledge and attitude of Saudi females towards screening
      mammography. MATERIAL AND METHODS: A sample of four hundred Saudi females were
      interviewed using a structured questionnaire. RESULTS: Positive family history of
      breast cancer was the most significant factor that was positively associated with
      individual knowledge and attitude towards screening mammography (p<0.00001).
      There was no significant association with the level of education. Poor knowledge
      and attitude were observed among 41.8% of all participants, especially in
      relation to not having mammography done or not wishing to have it done. There
      were 51 (12.8%) participants who had not had mammography done, but wished to have
      it, 25 (6.3%) participants who were undecided about having mammography done in
      the future, while 67 (16.8%) wished to have it done every one to two years.
      CONCLUSION: This study showed that there has been deficient knowledge and
      attitude towards screening mammography even among the highly educated, and
      stressed the need for health education on the importance of screening.

PMID- 23008655
TI  - Views of undergraduate students on objective structured clinical examination in
      neurology: a preliminary report.
AB  - OBJECTIVE: Obtain the undergraduate medical students' evaluation of an objective
      structured clinical examination (OSCE) formed by two stations in neurology.
      METHODS: The fifth-year medical students taking the neurology course at King
      Faisal University during the first rotation of academic year 1420-1421H (2000
      2001G) made the evaluation. The time for each station was seven minutes. After
      finishing the examination, each student completed a six-item questionnaire on
      coverage, question clarity, time, patients, educational usefulness and
      organization of the examination with yes, no or don't know responses. RESULTS: A
      total of 48 students (30 males and 18 females) took the examination. The average
      time to complete the examination for a group of 16 students was 2 hours. The
      responses were positive for clarity of questions and organization of the
      examination 41(85%), and allotted time 36(75%). Thirty-two students (67%) found
      the structured examination a useful educational experience. About half the
      students expressed their concern about the coverage of taught material and the
      number of patients seen in the examination as representative of those seen during
      the course, and 11 students (23%) requested more time. CONCLUSIONS: The students'
      response to the use of the structured clinical examination as an objective tool
      for evaluation of clinical skills in neurology was favorable and comparable to
      reports from other parts of the world. Improvement is required in the number of
      patients, coverage and allotted time to optimize outcome by improving content
      validity and reducing stress on participating patients.

PMID- 23008656
TI  - Biochemical assessment of home made fluids and their acceptability in the
      management of diarrhea in children in the gezira state, Sudan.
AB  - OBJECTIVES: To determine the biochemical constitution of homemade fluids and
      assess their acceptability and efficacy for the management of acute diarrhea in
      Sudanese children. MATERIAL AND METHODS: This is a cross-sectional study of 150
      children selected randomly. The fluids studied were 36 samples of sorghum-based
      solutions (nasha) and 10 samples of rice water. Samples were randomly collected
      from households and analyzed to determine the pH, carbohydrates, proteins, fat,
      crude fiber, ash and electrolytes (Na(+), K(+) and Cl(-)). RESULTS: In addition
      to being very useful for rehydration, the two fluids were found to contain
      considerable amounts of nutrients. The sodium and chloride contents of homemade
      fluids were found to be much lower than those of the WHO/UNICEF ORS (oral
      rehydration solution). These electrolytes can be adjusted by adding table salt (3
      3.5 g NaCl to one litre of sorghum-based solution and 2.3-2.6 g NaCl to one liter
      of rice water) to bring them to concentration comparable to that of the standard
      ORS. CONCLUSION: Homemade solutions can be modified by adding table salt to bring
      them to the standard ORS and can be used successfully to prevent dehydration.
      This will solve the problem of the availability of ORS and reduce morbidity and
      mortality from diarrhea.

PMID- 23008657
TI  - Healthy students - healthy nation.

PMID- 23008658
TI  - The impact of some demographic factors on the severity of asthma in children.
AB  - OBJECTIVE: To investigate the association between some demographic factors and
      the levels of severity among asthmatic children. METHOD: One hundred and twenty
      five asthmatic children aged between 6 months and 15 years were studied in
      pediatric and asthma clinics at King AbdulAziz University Hospital (KAUH). The
      assessment of clinical severity was based on the global strategy guidelines for
      asthma assessment and management. Subjects were grouped by age: infants (<=1
      year), toddlers (1-3 years), preschool or kindergarten (3-6 years), school (6-12
      years), and adolescents (12-15 years). Demographic data (age and sex) were
      analyzed for any statistical significance. RESULTS: Boys were 80 (64%) and
      predominated in all age groups except in infants. 10(8%) were infants, 22(17.6%)
      toddlers, 26 (20.8%) preschool or kindergarten, 49 (39.2%) school, and 18 (14.4%)
      adolescent. The levels of severity of asthma were intermittent 11 (8.8%), mild
      persistent 74 (59.2%), moderate persistent 33 (26.4%), and severe persistent 7
      (5.6%). Frequency and severity of asthma were significantly higher in boys than
      girls (P<0.05) and at school age compared to other age groups (P<0.05). 
      CONCLUSION #ENTITYSTARTX00026; RECOMMENDATION: This study demonstrated an
      increase in the frequency and severity of bronchial asthma in boys, particularly,
      those at school age. As stated in the literature, correlating demographic factors
      and clinical status can help in the prediction of the severity of asthma and
      possibly its outcome. This demands greater vigilance in the care of this group of
      asthmatics more than any others.

PMID- 23008659
TI  - Quality of life in a sample of hypertensive patients attending primary health
      care facilities in Al-khobar, saudi arabia.
AB  - BACKGROUND: Hypertension is one of the most prevalent chronic conditions in Saudi
      Arabia. It is the leading risk factor for cardiovascular diseases and a major
      reason for visits to clinic and prescription of medications. Inspite of this, the
      degree of its control is not to the optimum. This could be due to its impact on
      patients' quality of life (QOL). Impaired physical and psychological well-being
      may lead to non-compliance or even the withdrawal of treatment . The aim of this
      study was to assess QOL of hypertensive patients registered in Al-Khobar.
      METHODS: The QOL of hypertensive patients was compared with QOL of a control
      group. A total of 404 subjects (202 cases and 202 controls) were interviewed. The
      cases and controls were matched for age and sex. Patients' self-assessment of QOL
      was measured with an Arabic version of SF-36, a 36-item Short Form Health Survey
      Questionnaire encompassing two main dimensions, physical and mental. RESULTS: The
      QOL of hypertensive patients was substantially impaired in comparison to the
      control group. The mean scores for the physical component summary scale (PCS)
      were 39.3 and 50.8 for cases and controls respectively. The mean scores for the
      mental component summary scale (MCS) were 43.7 and 50.8 for cases and controls
      respectively. The burden of hypertension was concentrated in the physical
      dimension of health. Older age, female gender, unmarried patients, patients with
      hypertension complications, comorbid DM, use of Aldomet and shorter duration of
      hypertension were independently related to poorer QOL. The variability of the two
      summary measures explained by selected demographic and clinical characteristics
      was 24.3% and 10% for the PCS and MCS respectively. CONCLUSIONS AND
      RECOMMENDATIONS: The QOL of hypertensive patients was substantially impaired in
      comparison to the control group. Notably, the total explained variation of QOL by
      the selected characteristics was small, suggesting that the determinants of QOL
      are multi-factorial. Further research to explore the determinants and indices of
      QOL in hypertensive patients is warranted. From a clinical perspective, QOL
      should be considered in the monitoring of hypertensive patients to estimate the
      burden of hypertension and monitor their outcome.

PMID- 23008660
TI  - Medical laboratory technology program at king faisal university: a 10-year
      experience.
AB  - This paper documents the evolution of the Medical Laboratory Technology (MLT)
      program established in 1989 (1408/1409 H) at the College of Medicine and Medical
      Sciences, King Faisal University. The rationale, objectives, the general outline
      of the program as well as methods of instruction and evaluation are discussed.
      The internship period and future plans are also addressed. Two hundred and
      seventy (270) students had been enrolled in the program since its inception until
      September 2000. Ten batches (138 graduates) have already successfully graduated.
      One hundred and fifteen (83.3%) graduated technologists are employed in the
      different health sectors and educational institutions in the Kingdom.

PMID- 23008661
TI  - She wants it done.
AB  - OBJECTIVE: To compare ear piercing practices and complications arising therefrom
      in British and Sudanese children and to seek possible ethnic, cultural and
      environmental differences. SETTINGS: Maelor General Hospital, Wrexham, UK and Wad
      Medani Children Hospital, Wad Medani, Sudan. METHODS: Parents of a hundred
      British children and an equal number of Sudanese parents were requested to fill a
      questionnaire on ear piercing. All children were examined for possible local or
      systemic complications. RESULTS: All parents answered the questionnaire. Eighty
      eight (88%) of the British children were girls while all Sudanese children (100%)
      were girls. Eighty (80%) of the British children had had their ears pierced
      before they were 6 years old while 90% of Sudanese children had had their ears
      pierced below that age. The procedure was performed in both groups by non-medical
      staff. Local inflammation and allergic contact reactions were the commonest
      complications in both groups. Keloids were only encountered in the Sudanese
      children. A case of tetanus was encountered in the Sudanese group. CONCLUSION AND
      RECOMMENDATIONS: Ear piercing in both communities is performed at a very early
      age. This procedure is not without complications and the medical profession
      should advise safety in this practice. Earrings selected should be of non
      allergenic material. Regular application of an antiseptic to the site should be
      encouraged. The community should be made aware of the hazards and complications
      of ear piercing. With the awareness of these complications and guided with a set
      of rules, people may continue the practice (she may have it done). Health
      authorities in Sudan should formulate guidelines that will ensure hygienic
      measures and reduce complications.

PMID- 23008662
TI  - Hospital generated waste: an assessment of the awareness of hospital staff.
AB  - BACKGROUND: The provision of healthcare generates waste which can be detrimental
      to health and environment. Staff who provide healthcare ought to be aware of the
      proper handling and the system of management of healthcare waste used by
      different hospitals. MATERIALS AND METHODS: A survey of doctors, nurses and
      allied medical staff for their awareness of the hospital generation and handling
      of waste was conducted. A self-administered questionnaire was used. RESULTS: Lack
      of awareness, ignorance of policy and procedure on the handling of healthcare
      waste and failure to attend educational activities were major defects found among
      healthcare staff in the study. CONCLUSION: There is a need for a plan to improve
      the awareness of healthcare workers about hospital generated waste and its proper
      handling.

PMID- 23008664
TI  - Tips on searching the internet for medical information.
AB  - Searching for references is part of everyday life in medicine. Since the arrival
      of the Internet, it has provided great promise for clinicians because of its
      ready provision of access to large amounts of knowledge and information. But
      because of the overload of information, searching for particular information has
      now become a tedious time-consuming and frustrating task. This article describes
      effective ways, tips, tools, detailed search techniques and strategies for
      searching for medical information. It also lists some useful resource and
      database sites that can help in the search for accurate information.

PMID- 23008663
TI  - Doctor-patient communication: a skill needed in saudi arabia.
AB  - Doctor-patient communication is a skill essential for the satisfaction of the
      patients' needs and expectations. It involves an art that every practicing
      physician should have. The situations in health care delivery that demands good
      doctor-patient communication are many. Diabetes care, the management of
      hypertension, explaining serious disease diagnoses, prognosis, and investigative
      procedures are some of the common situations where good doctor-patient
      communication is very essential. Doctor-patient communication assumes a special
      status in Saudi Arabia where as a result of mixed ethnicity of the manpower in
      the health service and the expatriate community, there is a vast diversity of
      languages, health traditions and beliefs. The skill of doctor-patient
      communication can be developed and improved by the application of the principles
      of the patient-centered approach, the utilization of patient-oriented evidence
      that matters, and its inclusion in the undergraduate curriculum in the first few
      years of medical school. There should be continuous medical education programs
      for practicing doctors on the skills of doctor-patient communication through
      seminars and workshops. This would be a further step towards the improvement of
      the consumer's well-being.

PMID- 23008665
TI  - The medical uses of internet and how to stay current with internet.

PMID- 23008666
TI  - Primary health care in saudi arabia: its development and future prospectives.

PMID- 23008667
TI  - Attitudes of medical interns towards the practice of primary health care.
AB  - BACKGROUND: Training in different specialties should prepare young physicians to
      assume responsibilities in primary care. Training for the acquisition of the
      proper attitude for health care, should be given in the course of the training in
      different specialties. OBJECTIVE: To assess the attitudes of medical interns who
      have undergone rotation in the Department of Family and Community Medicine of a
      large university hospital, towards the provision of primary care. METHODS: A
      cross-sectional study incorporating a structured questionnaire was carried out on
      a sample of 106 interns; and 20 consultants were selected as a reference group.
      RESULTS: All medical interns almost unanimously endorsed continuous, coordinated,
      accessible and comprehensive care. In contrast, consultants less often supported
      the provision of such care for their own patients. CONCLUSIONS: Unless
      consultants change their attitudes towards the attributes of primary care, the
      quality of patient care as well as physician training would suffer.

PMID- 23008668
TI  - A study of group a streptococcal bacteria isolation from children less than 12
      years with acute tonsillitis, pharyngitis and healthy primary school children.
AB  - AIM: This study was carried out to assess the prevalence of Group A Streptococcal
      (GAS) bacteria in the throat specimens of children with tonsillitis and
      pharyngitis compared to healthy children of the same age group. METHODOLOGY: The
      study was a prospective one. Throat swabs were obtained from 73 children aged 1
      12 years diagnosed with acute tonsillitis and pharyngitis (sore throat and
      pyrexia >38.5 degrees C) visiting a pediatric outpatient clinic between December,
      1999 and April, 2000. In the same period throat swabs were obtained from 465
      healthy primary school children aged 6-12 years. GAS from patients was tested for
      sentivity to penicillin, erythromycin, and cefaclor. RESULTS: In children with
      tonsillitis and pharyngitis GAS was found in 29 out of 73 (40%). In healthy
      school children GAS was found in 15 out of 465 (3%).In the patients group GAS was
      sensitive to penicillin in 14(48%), erythromycin in 27(93%), and cefaclor in
      28(96%) CONCLUSION: Although the prevalence of GAS among healthy children was
      similar to international studies, the GAS infection was high among children with
      acute tonsillitis and pharyngitis. Sensitivity to penicillin was less than 50%
      and more than 90% for erythromycin and cefaclor. We recommend routine throat swab
      for children with acute tonsillitis and pharyngitis and the proper treatment of
      GAS positive patients to prevent further complications.

PMID- 23008669
TI  - Incidence of helicobacter pylori in dental plaque of saudi gastritis patients.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) was identified in dental plaque,
      raising the possibility of future gastritis and peptic ulceration. OBJECTIVE:
      This trial was to study the association between presence of H. pylori in dental
      plaque and in the stomachs of patients with gastritis; the effect of oral hygiene
      and periodontal condition on the stomach. PATIENTS AND METHODS: Seventy-five
      Saudi adult dyspeptic patients, together with 60 healthy persons as control. Two
      samples of dental plaque were taken from gingival crevice of deepest pocket. One
      sample was kept in Christensen's urea agar and incubated for H. pylori detection
      by rapid urease test. The second sample was kept in 5% sheep blood agar,
      chocolate agar and a selective medium to culture the H. pylori. Gastric urease
      test was done for the same patients. RESULTS: (1) Plaque urease test results
      showed 89% positive patients. (2) Dental plaque Index:- Mild dental plaque
      accumulation in 24%, moderate in 41%, while severe accumulation was in 35% of the
      patients. (3) Gingival Index: Showed mild, moderate and severe gingivitis in 17%,
      48% and 35% of patients, respectively. (4) Community periodontal index of
      treatment needs (CPITN): Showed gingivitis, mild periodontitis and moderate
      periodontitis in 50%, 23% and 27% of patients, respectively. (5)Gastric urease
      results: 87% of patients were positive. (6)All cultured samples results were
      negative CONCLUSION: The ability to detect H. pylori in dental plaque samples
      offers a potential for a noninvasive test for gastric infection and would lend
      support for oral spread of H. pylori as the princi-pal mode of transmission.
      However, the presence of H. pylori in dental plaque and in the stomach (in
      gastritis patients) could permit not only a target for therapeutic procedures but
      also a monitor-ing tool for the efficacy of therapy.

PMID- 23008670
TI  - Clinical pattern of acne vulgaris and its associated conditions in the eastern
      province of kingdom of saudi arabia: a hospital-based clinical study.
AB  - OBJECTIVE: This study aims to review the clinical pattern of acne vulgaris cases
      referred to one hospital in the Eastern Province. METHODS: Two hundred cases
      diagnosed in the Dermatology Department at King Fahad Hospital of the University
      (KFHU), Al-Khobar, Saudi Arabia were studied RESULTS: Inflammatory acne was the
      predominant type observed in both males and females (76% and, 79%, respectively).
      Seborrhea (greasy skin) was the most frequently associated condition 22 (11%)
      followed by dandruff 8 (4%). The difference between males and females was not
      statistically significant (p-value = 0.46, 0.93, respectively). In female
      patients, premenstrual flare was observed in 12 (9.8%), irregular period 5
      (4.1%), and hirsutism 3 (2.5%).

PMID- 23008671
TI  - Dietary misconceptions among diabetic patients in makka city, saudi arabia.
AB  - OBJECTIVES: To assess the prevalence of some dietary misconceptions among primary
      health care center-registered diabetic patients in Makka City, Saudi Arabia.
      METHODS: A sample of 1039 primary health care center- registered diabetic
      patients was interviewed using a structured questionnaire on diabetic diet 
      related misconceptions. A scoring system was used to document the frequency of
      misconceptions. The relationship of the misconceptions to socio-demographic and
      diabetes-related variables was assessed using chi-squared tests. RESULTS: Most
      patients (68.7%) had a high diet misconception score. More than half of the
      sample had the misconception that carbohydrates were to be completely eliminated
      from the diet, and only dried bread and bitter foods were to be consumed. Data
      included the belief in the consumption of honey and dates; the omission of
      snacks; belief in the carcinogenicity of the sugar substitutes; and obesity as a
      sign of good health. The score was significantly higher among males (p<0.01),
      patients older than 35 years (p<0.02), and among patients whose level of
      education was low (p<0.01). CONCLUSION: It is important to note that the rate of
      diet-related misconceptions among diabetics in Makka city is high. The study
      pointed to the target fraction of diabetic patients among whom these
      misconceptions prevailed. There is a need for constant motivation and appropriate
      education at frequent intervals to encourage better knowledge of the disease so
      that there is compliance to treatment.

PMID- 23008672
TI  - Evaluation of continuing medical education in Al-qasim, saudi arabia.
AB  - OBJECTIVE: To evaluate CME activities in Al-Qassim region in the Kingdom of Saudi
      Arabia METHODS: A study using a pre-structured questionnaire was conducted in Al
      Qassim, targeting physicians working in the hospitals. The survey was conducted
      in two phases. The first phase was conducted at the inception of the department
      of professional education and the second one year later. Questionnaires were
      given to a sample of physicians working in the hospitals. RESULTS: Mean CME hours
      in the region increased from 5.5(+/-5.9) to 14.2(+/-19.7), p=0.0001. 50% said
      that the CME should be presented differently. There was a need for regular
      courses (61%), departmental and bedside activities (52%) and visiting speakers
      (45%). Only 47% of the physicians were using the Internet. CONCLUSION: There is a
      need to shift from credit counting to a process that can yield professional
      development through practical courses and departmental activities. The use of the
      Internet in CME activities should be encouraged.

PMID- 23008673
TI  - The future of the curriculum of allied (applied) health sciences in saudi arabia.
AB  - BACKGROUND: Despite the dearth of allied health professionals in the Kingdom of
      Saudi Arabia (KSA), the demand for them has increased. Like any other geographic
      location, KSA, has its own pattern of diseases. Therefore, the curriculum of the
      health professionals should be appropriately designed to meet the health needs of
      hospitals and clinics. OBJECTIVES: To demonstrate that changes in the curriculum
      of Allied (Applied) Health Sciences in KSA are necessary, and how these changes
      should be implemented. This paper also recommends that these changes must: (1) be
      based on the current needs of the community, (2) satisfy the health requirements
      of the Saudi community as well as the realities of its health practices. The
      Allied Health Colleges must: (1) undertake a long-term review of the curriculum,
      (2) ensure that the curriculum reform is continuous, (3) target faculty
      development, (4) target student evaluation.

PMID- 23008674
TI  - Hospital generated waste: a plan for its proper management.
AB  - Hospitals are important sites for the generation of hazardous waste. Each
      hospital has its own profile for the generation and transportion of waste
      according to its location. It is extremely important to manage hospital generated
      waste properly in order to avoid health and environmental risks.This article
      reports the plan designed and used by the hospital waste management committee in
      King Fahad Hospital of the University , Alhkobar, Saudi Arabia, for the safe
      management of hospital generated waste starting from the collection areas to the
      final disposal procedure. The plan was in four stages: background information,
      identification of problems, intervention and monitoring. The possible solutions
      for problems encountered are suggested.This plan which was efficient and cost
      effective can be used in other medical establishments.

PMID- 23008675
TI  - New hope for hiv/aids patients: the case of a sudanese adult patient.

PMID- 23008676
TI  - Future of the arab family physician.

PMID- 23008677
TI  - Does the management of bronchial asthma by family physicians meet standards of
      the national protocol?
AB  - OBJECTIVES: Asthma is a common disease that is sometimes fatal. Its prevalence,
      morbidity and mortality are increasing. The objective of this paper was to
      evaluate the proficiency of primary care physicians in general knowledge,
      diagnosis, classification of severity and management of asthma along the
      guidelines of the Saudi National Asthma Protocol, and to analyze the association
      of their proficiency level with certain professional standards. METHODS: This was
      a cross-sectional study conducted in the Department of Family Medicine and the
      Main Air Base Clinic at the North-West Armed Forces Hospital in Tabuk City, Saudi
      Arabia from the 1(st) to the 29(th) of June 2001. All 44 primary care physicians
      working there at the time were enrolled in the study. A self-administered
      true/false questionnaire prepared by the Saudi National Asthma Scientific
      Committee was completed by all physicians. The Passing score was >= 50%. RESULTS:
      Only 39% of the physicians passed the test as a whole, with 66% passed in general
      knowledge, 70% in diagnosis, 48% in the classification of severity and 59% in the
      management of asthma. There was an association between significant achievement
      and Family Medicine Board Certification as well as some knowledge of the National
      Asthma Protocol (p >= 0.05). No association was observed with attendance of
      asthma training courses. There was positive significant correlation between the
      knowledge score, the management scores and the total scores of physicians.
      CONCLUSION: The level of awareness of the National Asthma Protocol among the
      primary care physicians was low (52%). Their proficiency in general knowledge,
      diagnosis, classification of severity and management was also low. A higher
      standard was associated with Family Medicine Board Certification. Further studies
      to identify the reasons for these deficiencies need to be carried out so that
      measures could be taken to rectify the situation.

PMID- 23008678
TI  - Expectations of saudi patients for medications following consultations in primary
      health care in riyadh.
AB  - BACKGROUND: Knowing patients' expectation for medication after each consultation
      is of the utmost importance in designing public education programs on the
      rational use of drugs. OBJECTIVE: To determine whether patients in Riyadh, Saudi
      Arabia, expect drugs after each primary care consultation. SUBJECTS AND METHODS:
      A sample of 985 Saudi patients aged 15 and above was randomly selected. A cross
      sectional survey was carried out at five randomly selected primary care centers,
      using a self-administered questionnaire distributed to patients before being seen
      by primary care doctors. RESULTS: Most patients (87.8%) always expect drug
      prescriptions. Eighty nine percent (88.9%) had been prescribed drugs in the
      previous consultation. Sixty six percent (66%) had received 2-3 drugs during
      their previous consultation. The majority thought it was too much. Seventy
      percent (70%) took all their prescribed drugs. Patients with intermediate and
      high school education had the highest compliance rate (32%). Twenty two percent
      (22%) thought it was always necessary to use a drug for an illness. The level of
      education of the majority of patients ranged from illiterate to various levels of
      pre-university education. CONCLUSION: Most Saudi patients expect drugs. General
      and specific health education should be given to both patients and doctors.

PMID- 23008679
TI  - Perception of body weight among saudi school children.
AB  - OBJECTIVES: The objectives of this study were to explore the perception of body
      weight among students in schools in Jeddah City and identify the main
      determinants of self-perceived obesity, weight management goals and practices.
      MATERIAL AND METHODS: Data were collected from a sample of Saudi school children
      of 42 boys' and 42 girls' schools in Jeddah city during the month of April 2000.
      Personal interviews were conducted to collect data on socio-demographic factors,
      food choices, perception of body weight, weight management goals and weight
      management practices, as well as the actual measurement of weight and height.
      Students were asked about their perception of their body weight [responses
      included: very underweight (thin), slightly underweight, about right weight,
      slightly overweight and grossly overweight (obese)]. Proportion, prevalence and
      95% confidence intervals were calculated. Multiple logistic regression models
      were fitted to calculate the adjusted odds ratio (OR) for an attempt to lose
      weight and weight management practices. RESULTS: The distribution of self
      perception of body size was nearly similar to the measured body mass index (BMI)
      classification except for the overweight students, where 21.3% perceived
      themselves, as slightly overweight and 5.5% as very overweight although 13.4%
      were actually overweight and 13.5% were obese by BMI standards. Approximately
      half the students took at least 3 pieces of fruit or fruit juice servings, and a
      third ate at least 4 vegetable servings per day. A third of the students managed
      to lose weight. This coincides with the proportion of those actually overweight
      and obese. Around 28.0% of the students ate less food, fat or calories, 31.0%
      took exercise and 17.6% were engaged in vigorous exercise to lose weight or
      prevent weight gain. Staying for at least 24 hours without food which is a
      potentially harmful means of weight control was practiced by 10.0% of students.
      Females were less likely than males to be overweight and obese but more likely to
      perceive themselves as grossly overweight and more likely to try to lose weight.
      Factors associated with efforts to lose weight by eating less fat or fewer
      calories were older age, high social class, being actually obese and perceiving
      oneself as being obese. Staying for at least 24 hours without eating was mainly
      practiced by females, older age groups, and the actually obese. Exercise was done
      mainly by the older age groups, those with educated and highly educated mothers,
      obese and perceiving oneself as being obese. Vigorous exercise was mainly
      performed by males, younger age groups, taking < 3 pieces of fruit or fruit juice
      servings per day, eating < 4 vegetable servings per day, and those perceiving
      themselves as obese. CONCLUSION: Overweight and obesity are prevalent among our
      youth and not all obese have a correct image of their body size. Highly
      recommended are intervention programs of education on nutrition starting in
      childhood through school age to promote and ensure healthy food choices, improve
      student's awareness of ideal body size and clinical obesity, encourage physical
      exercise but discourage potentially harmful weight control measures.

PMID- 23008680
TI  - Work-related assaults on nursing staff in riyadh, saudi arabia.
AB  - OBJECTIVE: To determine the extent of work-related violence against nurses in
      hospitals in Riyadh. MATERIALS AND METHODS: Through a cross sectional approach, a
      self administered questionnaire was offered to 500 active-duty nurses selected
      randomly. In addition to the demographic characteristics, the questionnaire
      inquired about exposure to workplace violence, hospital and department of
      employment at the time of exposure, characteristics of the assailant and nurses'
      perception of the causes of violence. RESULTS: Out of 434 respondents, 93 (21.4%)
      were males, and 341 (78.6%) females. The mean age was 36.1 +/- 7.97 years.
      Workplace violence was experienced by 235 (54.3%) nurses. Of these 93.2% were
      exposed to harsh insulting language, 32.8% to verbal threat, 28.1% to attempts of
      physical assault, 17.4% to sexual harassment and 16.2% to actual physical
      assault. Nurses working in psychiatry and emergency units had the highest rate of
      exposure to violence (84.3% & 62.1% respectively) Nurses perceived shortage in
      security personnel (82%), shortage in nursing staff (63%), language barrier
      (36.3%) and unrestricted movement of patients in hospitals (21.5%) as causes of
      their exposure to violence. RECOMMENDATIONS: improve security in hospitals by
      increasing the number of security officers on duty and increase the community's
      awareness of the problem.

PMID- 23008681
TI  - A comparison of psychiatric referrals within the teaching hospital with those
      from primary care and general hospitals in saudi arabia.
AB  - OBJECTIVE: This study aims at examining the pattern of psychiatric referrals with
      particular reference to (1) age and gender (2) source of referrals and (3)
      diagnosis of referred patients within a teaching hospital METHOD: Four hundred
      and twenty seven referrals (n=427) for psychiatric consultation within KKUH were
      selected prospectively by systematic randomization over a period of one year, and
      were compared with a general hospital (n=138) and primary health care (n=402)
      psychiatric referrals to a mental health facility. RESULTS: The age of referred
      patients across the three settings differed significantly and the male patients
      were slightly over-represented in the teaching hospital referrals. Pediatric
      clinics in the teaching hospital constituted significant sources of psychiatric
      referrals as compared to the general hospitals. Schizophrenic disorders and acute
      psychoses were significantly less among teaching hospital referred patients,
      whereas anxiety and mood disorders were much more common among teaching hospital
      and primary care patients. The number of personality disorders diagnosed in
      teaching hospital settings was significant. CONCLUSIONS: In Saudi Arabia, sources
      of psychiatric referrals and diagnostic patterns of mental disorders differ
      across the three levels, and this is comparable to international research on
      psychiatric referrals. Besides exploring other aspects of referral process,
      researchers at the three settings should carry out follow-up studies to assess
      the impact of psychiatric consultations on the global outcome of referred
      consultees.

PMID- 23008682
TI  - Are we ready for arabization in medical education?
AB  - OBJECTIVE: To obtain the views of faculty members of the College of Medicine,
      King Faisal University on Arabization of medical education. METHODS: A cross
      sectional study was conducted in the College of Medicine, King Faisal University,
      Dammam, between January and June 2001 using a standardized 41-item questionnaire
      to obtain the views of faculty members in both basic science and clinical
      departments on issues relating mainly to scientific research. The responses were
      recorded on a 5-point scale: strongly agree, agree, undecided, disagree and
      strongly disagree. A couple of questions were used to probe the issue of
      publications in Arabic and translations into Arabic. RESULTS: The response rate
      of faculty was 67% (74 of a total of 110 faculty members). The participating
      faculty members included 22 professors, 27 associate professors, 23 assistant
      professors and 2 lecturers belonging to 24 departments (6 basic sciences, 18
      clinical). Thirty- four members (45.9%) were in favor of Arabization and 40 (54%)
      were against. CONCLUSIONS: Faculty members form the backbone for the
      implementation of Arabization in medical education. The opinions obtained in this
      preliminary survey of the faculty of the College of Medicine at King Faisal
      University indicate that we are still far from achieving this goal in our medical
      education.

PMID- 23008683
TI  - Local Polynomial Regression for Symmetric Positive Definite Matrices.
AB  - Local polynomial regression has received extensive attention for the
      nonparametric estimation of regression functions when both the response and the
      covariate are in Euclidean space. However, little has been done when the response
      is in a Riemannian manifold. We develop an intrinsic local polynomial regression
      estimate for the analysis of symmetric positive definite (SPD) matrices as
      responses that lie in a Riemannian manifold with covariate in Euclidean space.
      The primary motivation and application of the proposed methodology is in computer
      vision and medical imaging. We examine two commonly used metrics, including the
      trace metric and the Log-Euclidean metric on the space of SPD matrices. For each
      metric, we develop a cross-validation bandwidth selection method, derive the
      asymptotic bias, variance, and normality of the intrinsic local constant and
      local linear estimators, and compare their asymptotic mean square errors.
      Simulation studies are further used to compare the estimators under the two
      metrics and to examine their finite sample performance. We use our method to
      detect diagnostic differences between diffusion tensors along fiber tracts in a
      study of human immunodeficiency virus.

PMID- 23008684
TI  - A review on bioadhesive buccal drug delivery systems: current status of
      formulation and evaluation methods.
AB  - Owing to the ease of the administration, the oral cavity is an attractive site
      for the delivery of drugs. Through this route it is possible to realize mucosal
      (local effect) and transmucosal (systemic effect) drug administration. In the
      first case, the aim is to achieve a site-specific release of the drug on the
      mucosa, whereas the second case involves drug absorption through the mucosal
      barrier to reach the systemic circulation. The main obstacles that drugs meet
      when administered via the buccal route derive from the limited absorption area
      and the barrier properties of the mucosa. The effective physiological removal
      mechanisms of the oral cavity that take the formulation away from the absorption
      site are the other obstacles that have to be considered. The strategies studied
      to overcome such obstacles include the employment of new materials that,
      possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer
      properties and the design of innovative drug delivery systems which, besides
      improving patient compliance, favor a more intimate contact of the drug with the
      absorption mucosa. This presents a brief description of advantages and
      limitations of buccal drug delivery and the anatomical structure of oral mucosa,
      mechanisms of drug permeation followed by current formulation design in line with
      developments in buccal delivery systems and methodology in evaluating buccal
      formulations.

PMID- 23008685
TI  - Pharmacokinetic study of niosome-loaded insulin in diabetic rats.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Encapsulation of human insulin in lipid
      vesicular systems such as niosomes was sought as a route to protect this protein
      against proteolytic enzymes and to improve its oral bioavailability. The purpose
      of this study was to assess the effect of insulin encapsulation in niosomes on
      oral bioavailability in diabetic rats. METHODS: Recombinant human insulin was
      entrapped in multilamellar niosomes composed of polyoxyethylene alkyl ether
      surfactants (Brij 52 and Brij 92) or sorbitan monostearate (Span 60) and
      cholesterol. The amount of insulin released in simulated intestinal fluid (SIF)
      and simulated gastric fluid (SGF) were measured at 37 degrees C. The protection
      of entrapped insulin against pepsin, alpha-chymotrypsin and trypsin were
      evaluated in comparison with free insulin solution. Diabetes was induced by IP
      injection of streptozotocin (65 mg/kg) in male wistar rats and effects of orally
      administered niosomes and subcutaneously injected insulin on hypoglycemia and
      elevation of insulin levels in serum were compared. RESULTS AND CONCLUSION: The
      extent and rate of insulin release from Brij 92 and Span 60 vesicles were lower
      than that of Brij 52 niosomes (P<0.05). Vesicles protected insulin in comparison
      with free insulin solution against proteolytic enzymes (P<0.05) significantly.
      Animals treated with oral niosome-encapsulated insulin (100 IU/kg) showed
      decreased levels of blood glucose and elevated serum insulin, which in the case
      of Brij 92 niosomes, hypoglycemic effect was significant (P<0.05). Niosomes were
      also stable in solubilizing bile salt solutions and could effectively prolong the
      release of insulin in both SGF and SIF. Results of this study showed that
      niosomes may be utilized as oral carriers of insulin; however, to increase
      bioavailability of insulin, further studies on the protease inhibitor co
      encapsulation in niosomal formulations might be helpful.

PMID- 23008686
TI  - The influence of active transport systems on morphine -6-glucuronide transport in
      MDCKII and MDCK-PGP cells.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Morphine-6-glucuronide (M6G) is a potent
      metabolite of morphine which has high penetration into the brain despite its high
      polarity, which could be the result of an active transport system involved in M6G
      transport through blood brain barrier. Examples of such transporters are p
      glycoprotein (PGP), probenecid-sensitive transport mechanism, multidrug
      resistance related protein 1-3, the organic anion transporter family, and the
      organic anion transporter polypeptide family. The aim of present study was to
      elucidate the mechanisms involved in transporting morphine's potent metabolite,
      M6G. METHODS: M6G permeability via two cell lines; MDCKII and MDCK-PGP, was
      compared with that of sucrose. M6G transport was examined in different
      concentrations and in the presence of inhibitors of different transport systems
      such as cyclosporine, digoxin and probenecid. M6G concentration was measured
      using ELISA assay. The method was sensitive, reliable and reproducible. RESULTS:
      The results confirmed that M6G could cross a layer of MDCK II or MDR-PGP cells
      more than sucrose could. It was also observed that M6G is a PGP transporter
      substrate. Its permeability was increased by the use of a PGP expressed cell
      line, and also in the presence of a strong PGP inhibitor. Digoxin related
      transporters such as Oatp2 may also involved in transport of M6G. M6G seemed to
      be a glucose transporter 1 substrate, but was not a substrate to probenecid
      sensitive transporters. MAJOR CONCLUSION: It is concluded that different
      transporters are responsible for M6G transports via different membrane, which
      could have effects on its pharmacokinetics or pharmacodynamics.

PMID- 23008687
TI  - Preparation and evaluation of pellets using acacia and tragacanth by extrusion
      spheronization.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Extrusion-spheronization is an
      established technique for the production of pellets for pharmaceutical
      applications. In this study, the feasibility and influence of the incorporation
      of acacia, by itself and in combination with tragacanth, on the ability of
      formulations containing 2 model of drugs (ibuprofen and theophylline) to form
      spherical pellets by extrusion-spheronization was investigated. MATERIAL AND
      METHODS: Formulations containing different ratios of acacia and tragacanth (8:2,
      9:1, and 10:0) and different drug concentrations (20%, 40%, and 60%) were
      prepared, on the basis of a 3(2) full factorial design. Pellet properties, such
      as aspect ratio, sphericity (image analysis), crushing strength and elastic
      modulus (mechanical tests), mean dissolution time, and dissolution profiles were
      evaluated. The effect of particular factors on responses was determined by linear
      regression analysis. RESULTS: The sphericity, drug release rate, and the
      mechanical properties of the pellets were affected by the amounts and types of
      the drugs, and the ratio of the gums. Acacia, relative to tragacanth, produced
      pellets with higher mechanical strength and a faster drug release rate. Addition
      of small amounts of tragacanth to ibuprofen formulations resulted in matrix
      pellets with slow drug release. CONCLUSION: The results showed that acacia and
      tragacanth can be used successfully as 2 natural binders in the pellet
      formulations.

PMID- 23008688
TI  - In vitro and In vivo characterization of the transdermal delivery of sertraline
      hydrochloride Films.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Sertraline hydrochloride is a selective
      serotonin reuptake inhibitor principally used in the treatment of major
      depressive disorder. To maintain the therapeutic plasma drug concentration of the
      drug for prolonged period, the transdermal drug delivery has been chosen as an
      alternative route of drug delivery. The pharmacokinetic properties of sertraline
      hydrochloride make it suitable for transdermal delivery. The purpose of the study
      was to investigate the effect of polymers and penetration enhancers on the
      transdermal delivery of the drug in order to improve its therapeutic efficacy.
      METHODS: In the preparation of films, Eudragit RL 100, Eudragit RS 100, hydroxy
      propyl methyl cellulose (HPMC) and ethyl cellulose were used as polymers. The
      films were characterized for thickness, tensile strength, drug content, moisture
      uptake, moisture content, water vapor transmission rate and drug release. The
      films exhibiting higher rates of drug release were subjected to study the effect
      of oleic acid and propylene glycol as penetration enhancers on skin permeation of
      sertraline hydrochloride. In vivo and skin irritation studies were performed for
      the optimized film. RESULTS: Films containing Eudragit RL 100, Eudragit RL 100
      and HPMC showed the highest drug release of 94.34% and 96.90% respectively in a
      period of 42 hrs. The release data fitted into kinetic equations, yielded zero
      order and fickian mechanism of drug release. There was a two-fold increase in
      skin permeation of sertraline hydrochloride in the presence of penetration
      enhancers in the film. The physical evaluation indicated the formation of smooth,
      flexible and translucent films. No skin irritation occurred on rabbit skin and
      the infrared studies showed the compatibility of the drug with the formulation
      excipients. The in vivo study revealed a constant plasma concentration of drug
      for long periods and the films containing penetration enhancers had achieved
      adequate plasma levels of the drug. CONCLUSIONS: The obtained results indicated
      the feasibility for transdermal delivery of sertraline hydrochloride using
      eudragit RL 100 and HPMC.

PMID- 23008689
TI  - Enhance transdermal delivery of flurbiprofen via microemulsions: Effects of
      different types of surfactants and cosurfactants.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Microemulsions are thermodynamically
      stable, clear dispersions of water, oil, surfactant, and cosurfactant. This study
      was aimed to develop flurbiprofen microemulsion for enhanced transdermal delivery
      and investigate the effects of different surfactants and cosurfactants on its
      delivery and phase behavior. METHOD: Various surfactant-cosurfactant mixtures in
      ratio of 2:1 (Smix) along with oleic acid (oil) were selected and phase diagrams
      were constructed. Six microemulsions each containing 5% drug, 5% oil, 56% Smix
      and 34% water, were prepared and compared for their permeation and phase
      behaviors to determine the effects of the type of Smix. RESULTS: In vitro
      transdermal permeation through rabbit skin of all microemulsions was high than
      saturated aqueous drug solution. Tween 20 and ethanol as Smix produced the
      highest flux amongst all the Smix, and were used to prepare formulations with
      different values of oil and Smix. While the type of surfactant did not affect the
      droplet size, propylene glycol as cosurfactant produced the largest droplets and
      highest viscosity. Decrease in oil or Smix concentration resulted in decrease of
      the droplet size and increase in permeation flux while decrease in viscosity also
      increased the permeation flux of microemulsions. Finally the selected
      microemulsion formulation comprising 5% flurbiprofen, 5% oleic acid, 46% Tween
      20:ethanol (2:1) and 44% water, showed the highest transdermal flux and caused no
      skin irritation. CONCLUSION: Type of surfactant and cosurfactant affect both the
      phase behavior and transdermal drug delivery of microemulsion; and results of
      this study showed that they are promising vehicles for improved transdermal
      delivery and sustained action of flurbiprofen.

PMID- 23008690
TI  - Solubility of pioglitazone hydrochloride in ethanol, N-methyl pyrrolidone,
      polyethylene glycols and water mixtures at 298.20  degrees K.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Solubility of pharmaceuticals is still a
      challenging subject and solubilization using cosolvents is the most common
      technique used in the pharmaceutical industry. The purpose of this study was
      reporting and modeling the experimental molar solubility of pioglitazone
      hydrochloride (PGZ-HCl) in binary and ternary mixtures of ethanol (EtOH), N
      methyl pyrrolidone (NMP), polyethylene glycols (PEGs) 200, 400, 600 and water
      along with the density of saturated solutions at 298.2  degrees K. METHODS: To
      provide a computational method, the Jouyban-Acree model was fitted to the
      solubilities of the binary solvents, and solubilities of the ternary solvents
      were back-calculated by employing the solubility data in mono-solvents. In the
      next step, the ternary interaction terms were added to the model and the
      prediction overall mean percentage deviation (MPD) of the ternary data was
      reduced. Also a previously proposed version of the model was used to predict the
      solubility of PGZ-HCl in binary and ternary mixtures employing the experimental
      solubility data in mono-solvents. RESULTS: The overall MPD of the model for
      fitting the binary data and predicted data of ternary solvents were 2.0 % and
      50.5 %, respectively. The overall MPD of the predicted solubilities in ternary
      solvents using the ternary interaction terms in the model was 34.2 %, and by
      using the proposed version of the Jouyban-Acree model for binary and ternary data
      the overall correlation and prediction errors were 18.0 and 15.0 %, respectively.
      CONCLUSION: The solubility of PGZ-HCl was increased by addition of EtOH, NMP,
      PEGs 200, 400 and 600 to aqueous solutions. The reported data extended the
      available solubility data of pharmaceuticals which are crucial in formulation of
      liquid dosage forms. The constants of the Jouyban-Acree model using the generated
      data are also reported which provides the possibility of solubility prediction in
      other solvent mixtures and temperatures.

PMID- 23008691
TI  - Modified ionic liquid cold-induced aggregation dispersive liquid-liquid
      microextraction combined with spectrofluorimetry for trace determination of
      ofloxacin in pharmaceutical and biological samples.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Ofloxacin is a quinolone synthetic
      antibiotic, which acts against resistant mutants of bacteria by inhibiting DNA
      gyrase. This antibacterial agent is widely used in the treatment of respiratory
      tract, urinary tract and tissue-based infections, which are caused by Gram
      positive and Gram-negative bacteria. In this work, an efficient modified ionic
      liquid cold-induced aggregation dispersive liquid-liquid microextraction (M-IL
      CIA-DLLME) was combined with spectrofluorimetry for trace determination of
      ofloxacin in real samples. METHODS: In this microextraction method, hydrophobic 1
      hexyl-3-methylimidazolium hexafluorophosphate ([Hmim] [PF(6)]) ionic liquid (IL)
      as a microextraction solvent was dispersed into a heated sample solution
      containing sodium hexafluorophosphate (NaPF(6)) (as a common ion) and the analyte
      of interest. Afterwards, the resultant solution was cooled in an ice-water bath
      and a cloudy condition was formed due to a considerable decrease of IL
      solubility. After centrifuging, the enriched phase was introduced to the
      spectrofluorimeter for the determination of ofloxacin. RESULTS AND MAJOR
      CONCLUSION: In this technique, the performance of the microextraction method was
      not influenced by variations in the ionic strength of the sample solution (up to
      30% w/v). Furthermore, [Hmim][PF(6)] IL was chosen as a green microextraction
      phase and an alternative to traditional toxic organic solvents. Different
      parameters affecting the analytical performance were studied and optimized. At
      optimum conditions, a relatively broad linear dynamic range of 0.15-125 ug l(-1)
      and a limit of detection (LOD) of 0.029 ug l(-1) were obtained. The relative
      standard deviation (R.S.D.) obtained for the determination of five replicates of
      the 10 ml solution containing 50 ug l(-1) ofloxacin was 2.7%. Finally, the
      combined methodology was successfully applied to ofloxacin determination in
      actual pharmaceutical formulations and biological samples.

PMID- 23008692
TI  - Carbenoxolone induces apoptosis and inhibits survivin and survivin-DeltaEx3 genes
      expression in human leukemia K562 cells.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Leukemia is a malignant disorder of the
      blood progenitor/stem cells which is characterized by abnormal proliferation of
      white blood cells. Although anti-cancer drugs induce apoptosis in cancerous
      cells, drug resistance is the significant problem mainly due to over-expression
      of inhibitors of apoptosis proteins (IAPs) such as survivin. In this content, it
      has been reported that an anti-inflammatory drug, Carbenoxolone (CBX), could
      induce apoptosis and growth inhibition in several types of cancerous cells. In
      the present study, effects of CBX on apoptosis and level of the expression of
      survivin gene and its DeltaEx3 splicing variant have were evaluated in K562
      cells. METHODS: K562 cells were cultured and treated with different
      concentrations of CBX (50-300 uM) at different time intervals (12-48 hrs). Trypan
      blue exclusion test was used to evaluate cell viability. Fluorescent microscopy
      (Acridine Orange/Ethidium Bromide double staining) and DNA fragmentation assay
      were used to study apoptosis. The expression level of survivin and its DeltaEx3
      splice variant were studied by RT-PCR. RESULTS AND MAJOR CONCLUSION: It was found
      that both growth inhibition and apoptosis occurred in K562 cells. In addition,
      down-regulation of survivin and survin-DeltaEx3 were observed, after 2-4 hrs
      treatment with 150 uM of CBX. However, the expression level of survivin and its
      DeltaEx3 splice variant increased in subsequent time (6-12 hrs) nearly to the
      level of control cells. From the results of this study, it may be concluded that
      CBX can be considered as a candidate for further studies in CML treatment,
      especially in the case of drug-resistant leukemia cells.

PMID- 23008693
TI  - 14,15-Epoxyeicosatrienoic acid induces the proliferation and anti- apoptosis of
      human carcinoma cell.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: Epoxyeicosatrienoic acids (EETs), which
      are cytochrome P450 epoxygenase metabolites of arachidonic acid, have anti
      inflammatory effects, modulate smooth muscle proliferation, and inhibit smooth
      muscle migration. This study was designed to determine whether exogenous EETs
      have any effect on the cell proliferation and apoptosis of carcinoma cell as well
      as the possible signaling pathways of EETs in this regulation. METHODS: The
      effects of EETs on the proliferation and anti-apoptosis of human carcinoma cells
      were measured by MTT assay and flowcytometric analysis, and the regulation of
      PPARgamma, epithelial growth factor receptor (EGFR), extracellular signal
      regulated kinase (ERK), phosphatidylinositol 3 (PI3)-Kinase/AKT pathways was
      investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and
      western blot analysis. RESULTS: Results of this study suggested that 14, 15-EET
      may activate the expression of PPARgamma in Tca-8113 cells. 14,15-EET may
      stimulate cell proliferation, and increase the percentage of cells during S-G2-M
      phase in Tca-8113 cells significantly. The levels of EGFR, ERK, and PI3
      kinase/AKT proteins were significantly induced by treatment of 14, 15-EET and
      14,15-EET/AUDA, but no significant changes were observed by addition of GW9662.
      CONCLUSION: These findings suggest that exogenous 14,15-EET has potent inhibitory
      effect on proliferation, and could induce apoptosis in Tca-8113 cell, and these
      changes are related to the expression of PPARgamma, the activation of EGFR, ERK,
      and PI3 kinase/AKT proteins.

PMID- 23008694
TI  - Systematic protein-protein docking and molecular dynamics studies of HIV-1 gp120
      and CD4: insights for new drug development.
AB  - BACKGROUND AND THE PURPOSE OF THE STUDY: The interactions between HIV-1 gp120 and
      mutated CD4 proteins were investigated in order to identify a lead structure for
      therapy based on competitive blocking of the HIV binding receptor for human T
      cells. Crystal structures of HIV gp120-CD4 complexes reveal a close interaction
      of the virus receptor with CD4 Phe43, which is embedded in a pocket of the virus
      protein. METHODS: This study applies computer simulations to determine the best
      binding of amino acid 43 CD4 mutants to HIV gp120. Besides natural CD4, three
      mutants carrying alternate aromatic residues His, Trp and Tyr at position 43 were
      investigated. Several docking programs were applied on isolated proteins based on
      selected crystal structures of gp120-CD4 complexes, as well as a 5 ns molecular
      dynamics study on the protein complexes. The initial structures were minimized in
      Gromacs to avoid crystal packing effects, and then subjected to docking
      experiments using AutoDock4, FireDock, ClusPro and ZDock. In molecular dynamics,
      the Gibbs free binding energy was calculated for the gp120-CD4 complexes. The
      docking outputs were analyzed on energy within the respective docking software.
      RESULTS AND CONCLUSION: Visualization and hydrogen bonding analysis were
      performed using the Swiss-PdbViewer. Strong binding to HIV gp120 can be achieved
      with an extended aromatic group (Trp). However, the sterical demand of the
      interaction affects the binding kinetics. In conclusion, a ligand for an
      efficient blocking of HIV gp120 should involve an extended but conformational
      flexible aromatic group, i.e. a biphenyl. A docking study on biphenylalanine-43
      confirms this expectation.

PMID- 23008695
TI  - Two cases of focal choroidal excavation detected by spectral-domain optical
      coherence tomography.
AB  - PURPOSE: To report the clinical findings of 2 patients with focal choroidal
      excavation in the macula detected by spectral-domain optical coherence tomography
      (SD-OCT). METHODS: Three eyes of 2 patients with a focal macular choroidal
      excavation detected by SD-OCT were studied. The eyes were examined by fundus
      autofluorescence (FAF), fluorescein angiography, fundus-related microperimetry,
      and multifocal electroretinography (mfERG). RESULTS: In spite of a complaint of
      metamorphopsia, the visual acuity was normal in 2 eyes. SD-OCT demonstrated a
      choroidal excavation in the macula but the foveal contour was normal in 3 eyes.
      The excavation involved the outer retinal layers up to the external limiting
      membrane in all eyes, and a type 2 secondary choroidal neovascularization (CNV)
      developed in 1 of the 3 eyes. There were areas of hypoautofluorescence in the FAF
      images, and areas of decreased retinal sensitivity determined by microperimetry.
      These areas corresponded to the choroidal excavation in all eyes. The P1
      amplitudes of the mfERGs were decreased in the fovea of 1 eye without a CNV.
      CONCLUSIONS: The choroidal excavation remained stable for 3 years in 2 eyes, a
      secondary CNV developed in 1 eye during the course of the disease. More cases and
      longer follow-up periods will be necessary to determine the etiology, clinical
      course, and visual prognosis of eyes with a choroidal excavation.

PMID- 23008696
TI  - PPARalpha-Independent Arterial Smooth Muscle Relaxant Effects of PPARalpha
      Agonists.
AB  - We sought to determine direct vascular effects of peroxisome proliferator
      activated receptor alpha (PPARalpha) agonists using isolated mouse aortas and
      middle cerebral arteries (MCAs). The PPARalpha agonists GW7647, WY14643, and
      gemfibrozil acutely relaxed aortas held under isometric tension and dilated
      pressurized MCAs with the following order of potency: GW7647?WY14643>gemfibrozil.
      Responses were endothelium-independent, and the use of PPARalpha deficient mice
      demonstrated that responses were also PPARalpha-independent. Pretreating arteries
      with high extracellular K(+) attenuated PPARalpha agonist-mediated relaxations in
      the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (K(ATP))
      channel blocker glibenclamide also impaired relaxations whereas the other K(+)
      channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas,
      GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase
      (sGC), and inhibition of sGC with ODQ blunted relaxations to PPARalpha agonists.
      In the MCA, dilations were inhibited by the protein kinase C (PKC) activator,
      phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute,
      nonreceptor-mediated relaxant effects of PPARalpha agonists on smooth muscle of
      mouse arteries. Responses to PPARalpha agonists in the aorta involved K(ATP)
      channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to
      contribute to the response.

PMID- 23008697
TI  - Simple cystatin C formula for estimation of glomerular filtration rate in
      overweight patients with diabetes mellitus type 2 and chronic kidney disease.
AB  - In clinical practice the glomerular filtration rate (GFR) is estimated from serum
      creatinine-based equations like the Cockcroft-Gault formula (C&G) and
      Modification of Diet in Renal Disease formula (MDRD). Recently, serum cystatin C
      based equations, the newer creatinine formula (The Chronic Kidney Disease
      Epidemiology Collaboration formula (CKD-EPI)), and equation that use both serum
      creatinine and cystatin C (CKD-EPI creatinine & cystatin formula) were proposed
      as new GFR markers. Present study compares serum creatinine-based equations,
      combined (including both serum creatinine and cystatin C) equation, and serum
      simple cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in
      113 adult overweight Caucasians with diabetes mellitus type 2 (DM2) and chronic
      kidney disease (CKD). The results of present study demonstrated that the simple
      cystatin C formula could be a useful tool for the evaluation of renal function in
      overweight patients with DM2 and impaired kidney function in daily clinical
      practice in hospital and especially in outpatients. Despite the advantages of the
      simple cystatin C formula, cystatin C-based equations cannot completely replace
      the "gold standard" for estimation of the GFR in a population of DM2 patients
      with CKD, but may contribute to a more accurate selection of patients requiring
      such invasive and costly procedures.

PMID- 23008698
TI  - Glibenclamide induces collagen IV catabolism in high glucose-stimulated mesangial
      cells.
AB  - We have shown the full prevention of mesangial expansion in insulin-deficient
      diabetic rats by treatment with clinically-relevant dosages of glibenclamide
      (Glib). Studies in mesangial cells (MCs) also demonstrated reduction in the high
      glucose (HG)-induced accumulation of collagens, proposing that this was due to
      increased catabolism. In the present study, we investigated the signaling
      pathways that may be implicated in Glib action. Rat primary MCs were exposed to
      HG for 8 weeks with or without Glib in therapeutic (0.01 MUM) or supratherapeutic
      (1.0 MUM) concentrations. We found that HG increased collagen IV protein
      accumulation and PAI-1 mRNA and protein expression, in association with decreased
      cAMP generating capacity and decreased PKA activity. Low Glib increased collagen
      IV mRNA but fully prevented collagen IV protein accumulation and PAI-1
      overexpression while enhancing cAMP formation and PKA activity. MMP2 mRNA,
      protein expression and gelatinolytic activity were also enhanced. High Glib was,
      overall, ineffective. In conclusion, low dosage/concentration Glib prevents HG
      induced collagen accumulation in MC by enhancing collagen catabolism in a cAMP
      PKA-mediated PAI-1 inhibition.

PMID- 23008700
TI  - Peritoneal metastases.

PMID- 23008699
TI  - Management of patients with atopic dermatitis: the role of emollient therapy.
AB  - Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing
      number of young children. Genetic, immune, and environmental factors interact in
      a complex fashion to contribute to disease expression. The compromised stratum
      corneum found in atopic dermatitis leads to skin barrier dysfunction, which
      results in aggravation of symptoms by aeroallergens, microbes, and other insults.
      Infants-whose immune system and epidermal barrier are still developing-display a
      higher frequency of atopic dermatitis. Management of patients with atopic
      dermatitis includes maintaining optimal skin care, avoiding allergic triggers,
      and routinely using emollients to maintain a hydrated stratum corneum and to
      improve barrier function. Flares of atopic dermatitis are often managed with
      courses of topical corticosteroids or calcineurin inhibitors. This paper
      discusses the role of emollients in the management of atopic dermatitis, with
      particular emphasis on infants and young children.

PMID- 23008701
TI  - Methylation and Expression of Retinoblastoma and Transforming Growth Factor-beta1
      Genes in Epstein-Barr Virus-Associated and -Negative Gastric Carcinomas.
AB  - Background. Retinoblastoma (RB) and transforming growth factor-beta1 (TGF-beta1)
      are important tumor-related factors. Methods. A series of 30 EBV-associated
      gastric carcinoma (EBVaGC) and 38 matched EBV-negative gastric carcinoma (EBVnGC)
      tissues were examined for the promoter methylation of RB by methylation-specific
      PCR (MSP) method. The expression of RB and TGF-beta1 in gastric carcinoma tissues
      was detected by immunohistochemistry. Results. The methylation rate of RB gene in
      EBVaGC and EBVnGC was 80.0% (24/30) and 50.0% (19/38), respectively. The
      difference of RB methylation rate between EBVaGC and EBVnGC was significant
      (chi(2) = 6.490, P = 0.011). There was no significant difference for RB
      expression between EBVaGC (43.3%, 13/30) and EBVnGC (63.2%, 24/38), and also for
      TGF-beta1 between EBVaGC (56.7%, 17/30) and EBVnGC (63.2%, 24/38). RB methylation
      was not reversely correlated with RB expression in gastric carcinoma tissues
      (chi(2) = 2.943, P = 0.086, r = 0.208). RB methylation, loss expression of RB,
      and TGF-beta1 expression were significantly associated with tumor invasion and
      lymph node metastasis (P < 0.05), but was not associated with sex, age,
      histological subtype (differentiation status) and tumor location. Conclusions.
      Methylation of RB is a common event in gastric carcinomas and EBV induces
      methylation of RB in EBVaGC, which may contribute to the development of gastric
      carcinomas. EBV has no significant effect on induction of TGF-beta1 expression.
      Detection of RB methylation, RB expression, and TGF-beta1 expression may be
      helpful to judge the status of tumor invasion and lymph node metastasis in
      gastric carcinomas.

PMID- 23008703
TI  - Personalized cancer therapy for urological cancers: from bench to bedside and
      back.

PMID- 23008704
TI  - Managing Patient Factors in the Assessment of Swallowing via Telerehabilitation.
AB  - Undoubtedly, the identification of patient suitability for a telerehabilitation
      assessment should be carried out on a case-by-case basis. However, at present
      there is minimal discussion of how telerehabilitation systems can accommodate and
      adapt to various patient factors, which may pose challenges to successful service
      delivery. The current study examines a subgroup of 10 patients who underwent an
      online assessment of their swallowing difficulties. Although all assessments were
      completed successfully; there were certain patient factors, which complicated the
      delivery of the online assessment session. The paper presents a discussion of the
      main patient factors observed in this cohort including the presence of speech
      and/or voice disorders, hearing impairment, dyskinesia, and behavioural and/or
      emotional issues and examines how the assessment session, the telerehabilitation
      system, and the staff involved were manipulated to accommodate these patient
      factors. In order for telerehabilitation systems to be more widely incorporated
      into routine clinical care, systems need to have the flexibility and design
      capabilities to adjust and accommodate for patients with varying levels of
      function and physical and psychological comorbidities.

PMID- 23008702
TI  - Central dopaminergic system and its implications in stress-mediated neurological
      disorders and gastric ulcers: short review.
AB  - For decades, it has been suggested that dysfunction of dopaminergic pathways and
      their associated modulations in dopamine levels play a major role in the
      pathogenesis of neurological disorders. Dopaminergic system is involved in the
      stress response, and the neural mechanisms involved in stress are important for
      current research, but the recent and past data on the stress response by
      dopaminergic system have received little attention. Therefore, we have discussed
      these data on the stress response and propose a role for dopamine in coping with
      stress. In addition, we have also discussed gastric stress ulcers and their
      correlation with dopaminergic system. Furthermore, we have also highlighted some
      of the glucocorticoids and dopamine-mediated neurological disorders. Our
      literature survey suggests that dopaminergic system has received little attention
      in both clinical and preclinical research on stress, but the current research on
      this issue will surely identify a better understanding of stressful events and
      will give better ideas for further efficient antistress treatments.

PMID- 23008705
TI  - A Quantitative Assessment of Tremor and Ataxia in Female FMR1 Premutation
      Carriers Using CATSYS.
AB  - The fragile X-associated tremor/ataxia syndrome (FXTAS) is a relatively common
      cause of balance problems leading to gait disturbances in older males (40%) with
      the premutation. FXTAS is less common in females. We utilized the CATSYS system,
      a quantitative measure of movement, in 23 women with FXTAS (mean age 62.7; SD
      12.3), 90 women with the premutation without FXTAS (mean age 52.9; SD 9.4), and
      37 controls (mean age 56.53; SD 7.8). CATSYS distinguished differences between
      carriers with and without FXTAS in postural tremor, postural sway, hand
      coordination, and reaction time tasks. Differences were also seen between
      carriers without FXTAS and controls in finger tapping, reaction time, and one
      postural sway task. However, these differences did not persist after statistical
      correction for multiple comparisons. Notably, there were no differences across
      groups in intention tremor. This is likely due to the milder symptoms in females
      compared to males with FXTAS.

PMID- 23008706
TI  - Does the serum testosterone level have a relation to coronary artery disease in
      elderly men?
AB  - Background. The low serum level of testosterone in the elderly subjects may
      contribute to coronary artery disease (CAD). Our aim is to study serum levels of
      free testosterone in elderly men with CAD. Subjects and Methods. This study was
      conducted on 100 elderly males with CAD, one half of them was presented with ACS
      (with mean age 69.6 +/- 2.44 year), and the other half was presented with stable
      CAD (with mean age 69.42 +/- 2.14 year), in addition to 50 apparently healthy
      elderly males (with mean age 69.06 +/- 1.64 year) as a control group. We detected
      the levels of serum free testosterone, cortisol, fibrinogen, plasminogen
      activator inhibitor-1(PAI-1), high sensitive C-reactive protein(hsCRP),
      interleukin-6(IL-6). Results. Cases with CAD had significant lower values of free
      testosterone and HDL-c, but they had significant higher values of cortisol,
      fibrinogen, PAI-1, IL-6, hsCRP, in comparison to control group. Cases with ACS
      had significant higher values of cortisol, hsCRP, IL-6, fibrinogen, PAI-1, total
      cholesterol and BMI more than those with stable CAD. The free testosterone had
      significant negative correlation with fibrinogen, PAI-1, hsCRP and IL-6 in both
      groups of patients. Conclusion. The lower value of serum free testosterone in
      elderly male subjects may contribute to CAD.

PMID- 23008707
TI  - Apathy in the elderly: from assessment to treatment.

PMID- 23008708
TI  - Antibiotic Resistance of Escherichia coli Serotypes from Cochin Estuary.
AB  - This study aimed at detecting the prevalence of antibiotic-resistant serotypes of
      Escherichia coli in Cochin estuary, India. E. coli strains were isolated during
      the period January 2010-December 2011 from five different stations set at Cochin
      estuary. Water samples from five different stations in Cochin estuary were
      collected on a monthly basis for a period of two years. Isolates were serotyped,
      antibiogram-phenotyped for twelve antimicrobial agents, and genotyped by
      polymerase chain reaction for uid gene that codes for beta-D-glucuronidase. These
      E. coli strains from Cochin estuary were tested against twelve antibiotics to
      determine the prevalence of multiple antibiotic resistance among them. The
      results revealed that more than 53.33% of the isolates were multiple antibiotic
      resistant. Thirteen isolates showed resistance to sulphonamides and two of them
      contained the sul 1 gene. Class 1 integrons were detected in two E. coli strains
      which were resistant to more than seven antibiotics. In the present study, O
      serotyping, antibiotic sensitivity, and polymerase chain reaction were employed
      with the purpose of establishing the present distribution of multiple antibiotic
      resistant serotypes, associated with E. coli isolated from different parts of
      Cochin estuary.

PMID- 23008709
TI  - A high-throughput computational framework for identifying significant copy number
      aberrations from array comparative genomic hybridisation data.
AB  - Reliable identification of copy number aberrations (CNA) from comparative genomic
      hybridization data would be improved by the availability of a generalised method
      for processing large datasets. To this end, we developed swatCGH, a data analysis
      framework and region detection heuristic for computational grids. swatCGH
      analyses sequentially displaced (sliding) windows of neighbouring probes and
      applies adaptive thresholds of varying stringency to identify the 10% of each
      chromosome that contains the most frequently occurring CNAs. We used the method
      to analyse a published dataset, comparing data preprocessed using four different
      DNA segmentation algorithms, and two methods for prioritising the detected CNAs.
      The consolidated list of the most commonly detected aberrations confirmed the
      value of swatCGH as a simplified high-throughput method for identifying
      biologically significant CNA regions of interest.

PMID- 23008710
TI  - Osteoarticular changes in acromegaly.
AB  - Acromegaly is caused by hypersecretion of growth hormone (GH) and consequently of
      insulin-like growth factor-I (IGF-1) due to pituitary tumor. Other causes, such
      as increased growth-hormone releasing hormone (GHRH) production, ectopic GHRH
      production, and ectopic GH secretion, are rare. Growth hormone and IGF-1 play a
      role in the regulation of bone metabolism, but accurate effect of growth hormone
      excess on bone is not fully explained. The issue of osteoarticular manifestations
      is still very actual, due to development of complications in the majority of
      patients with acromegaly. Traditionally, acromegaly is considered as a cause of
      secondary osteoporosis. Nowadays, it is discussed if BMD as predictor of
      osteoporotic fractures in acromegalic patient is decreased or even normal. Thus,
      bone quality remains to be more important in assessment of fracture risk. GH
      excess leads to increased bone turnover, defined by changes of bone markers. The
      articular manifestations are frequent clinical complications and may be present
      as the earliest symptom in a significant proportion of acromegalic patients.
      Articular manifestations are the main causes of morbidity and immobility of these
      patients, and they are persistent even after successful treatment. Quick
      recognition of osteoarticular changes and aiming the therapy lead to decrease in
      complication number.

PMID- 23008711
TI  - Diagnostic Significance of Intracystic Nodules on MRI in Rathke's Cleft Cyst.
AB  - Background and Purpose. To explore strategies for the diagnosis and treatment of
      Rathke's cleft cyst (RCC). Methods. The medical records of 24 patients with
      sellar RCC were retrospectively reviewed. Two patients had concomitant pituitary
      adenoma, 2 underwent transcranial surgery, and 22 underwent transsphenoidal
      surgery. The clinical features, especially the findings of intracystic nodules on
      MRI, were evaluated and compared with the pathological findings. Results.
      Preoperatively, only 2 patients were diagnosed with RCC or suspected RCC. Pre-
      and postoperative MRI images revealed 10 intracystic nodules in 9 (37.5%)
      patients. Two nodules had bull's eyelike changes. The signal intensity of the
      intracystic nodules varied on T1- and T2-weighted images. Not all nodules on T2
      weighted images were visualized. Postoperative MRI revealed recurrence or
      residual lesion in 5 patients; none had new symptoms and a second surgery was not
      required. Conclusions. Identifying intracystic nodules is important in patients
      with sellar cystic lesions. Bull's eyelike change in an intracystic nodule on
      MRI, which is reported here for the first time, potentially might have value for
      confirming the diagnosis.

PMID- 23008712
TI  - Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies
      and a Critical Reappraisal of Available Evidence.
AB  - Background. Randomized studies have shown different magnitude of bevacizumab
      benefit in the treatment of advanced breast cancer. Regulatory agencies have
      modified bevacizumab treatment indications across different regions. In this
      study, we perform a meta-analysis of phase III studies aiming to interrogate the
      magnitude of bevacizumab benefit for the treatment of first-line HER2-negative
      metastatic breast cancer (MBC). Methods. Data from studies E2100, AVADO and
      RIBBON-1 were used to calculate the benefit of bevacizumab in terms of tumor
      overall response rate (ORR), progression-free survival (PFS), overall survival
      (OS), and toxicities. Combined statistical estimates of hazard ratios (HR) and
      odds ratios were calculated using fixed-effects or random-effects models.
      Results. A total of 2,695 patients were evaluated. Combining bevacizumab with
      different chemotherapy backbones resulted in a 30% risk reduction of PFS events
      (HR = 0.70; 95% confidence interval [CI], 0.57-0.86) and increased ORR (odds
      ratio 1.81; 95% CI, 1.53-2.14). No OS benefit could be demonstrated (HR = 0.95;
      95% CI, 0.85-1.06). Bevacizumab significantly increased the incidence of adverse
      events such as proteinuria, hypertension and cardiovascular events. Conclusions.
      Bevacizumab combined with chemotherapy in the first-line treatment of MBC
      significantly improved ORR and PFS, but also increased grade 3-4 toxicities. No
      significant OS advantage was observed.

PMID- 23008713
TI  - Risk of Late Mortality and Second Malignant Neoplasms among 5-Year Survivors of
      Young Adult Cancer: A Report of the Childhood, Adolescent, and Young Adult Cancer
      Survivors Research Program.
AB  - We conducted a population-based retrospective study to assess the long-term risks
      of overall and cause-specific mortality and second malignant neoplasm (SMN) among
      survivors of young adult cancer compared to the risk in British Columbia (BC)
      population and to evaluate the effects of demographic and clinical factors on
      risk. 1248 5-year survivors of young adult cancer diagnosed 1970-1995 between 20
      and 24 years of age were identified from the BC Cancer Registry and followed to
      the end of 2007. Standardized mortality ratios (SMRs) and standardized incidence
      ratios (SIRs) were calculated. The Cox proportional hazards model was used to
      estimate the effects of different demographic and disease-related characteristics
      on the risk of death and SMN. A total of 138 deaths and 62 SMNs were observed
      during follow-up. The overall SMR was 5.9 (95% CI 4.9-6.9) and the absolute
      excess risk was 5.3 per 1,000 person-years. The overall SIR was 3.0 (95% CI 2.3
      3.8). Treatment with radiation resulted in increased risks of death and SMN.
      These observed increased risks emphasize the importance of prevention,
      surveillance, and treatment of late effects in survivors of young adult cancers.

PMID- 23008715
TI  - Susceptibility of enamel treated with bleaching agents to mineral loss after
      cariogenic challenge.
AB  - Objectives. Controversial reports exist whether bleaching agents cause a
      susceptibility to demineralization. The aim of this study was to compare the
      calcium loss of enamel treated with different bleaching agents and activation
      methods. Method and Materials. The specimens obtained from human premolars were
      treated in accordance with manufacturer protocols; 10% carbamide peroxide, 38%
      hydrogen peroxide light-activated, 38% hydrogen peroxide laser-activated, and no
      treatment (control). After cariogenic challenge calcium concentrations were
      determined by Inductively Coupled Plasma Mass Spectrometry. Results. No
      differences were found between the calcium loss of the laser-activated group and
      10% carbamide peroxide group (p > 0.05). However, the differences between laser
      activated and control groups were statistically significant (p < 0.05). The
      differences between 10% carbamide peroxide and the control group were not
      significant (p > 0.05). On the other hand, the light-activated group showed a
      significantly higher calcium loss compared with the other groups (p < 0.05).
      Conclusions. The results show that bleaching agents may cause calcium loss but it
      seems to be a negligible quantity for clinical aspects.

PMID- 23008716
TI  - Dental implants in posterior maxilla: diagnostic and treatment aspects.

PMID- 23008718
TI  - Primary hydatid cyst of the thyroid gland.
AB  - Primary hydatid cyst of thyroid gland is an exceptional localization even in
      Morocco where echinococcal disease is endemic. A 23-year-old woman presented with
      multiples cystic lesions of the thyroid revealed by neck mass and dyspnea. She
      underwent a subtotal thyroidectomy. The diagnosis of hydatid cyst was made
      preoperatively and was confirmed by histological studies. Further investigation
      failed to identify any other evidence of systemic hydatidosis. The patient has
      remained asymptomatic for 24 months after surgery. The possibility of hydatid
      disease, though rare, should be always kept in mind, for patients with cystic
      lesions of the thyroid, because a needle aspiration biopsy is a potentially
      harmful procedure.

PMID- 23008719
TI  - Acute abdomen in a patient with cancer pain on oxycodone.
AB  - Opioids are a mainstay of treatment for moderate to severe cancer pain. At
      present, oxycodone has fewer adverse effects compared to morphine and is widely
      used for cancer pain therapy. The adverse effects of oxycodone are similar to
      morphine and include constipation, nausea, and sedation. However, acute abdominal
      pain is rarely seen. Here, we describe a cancer patient presenting with acute
      abdomen with stercoral diarrhea. A 54-year-old man with squamous cell carcinoma
      of the external auditory canal had been taking oxycodone for pain relief. The
      patient had taken oxycodone for several months and had never complained of either
      diarrhea or constipation. After an increase in the dosage of oxycodone, he
      complained of abdominal distension and constipation. After being administered a
      laxative, he complained of diarrhea and severe abdominal pain. He visited the
      emergency department and was diagnosed with acute colonic obstruction caused by
      severe constipation. He self-medicated with oxycodone at dosages of up to 180
      mg/day, and this abrupt increase of oxycodone caused stercoral diarrhea. Finally,
      total blockage of stool developed, resulting in acute abdomen.

PMID- 23008714
TI  - Current understanding of lifestyle and environmental factors and risk of non
      hodgkin lymphoma: an epidemiological update.
AB  - The incidence rates of non-Hodgkin lymphoma (NHL) have steadily increased over
      the last several decades in the United States, and the temporal trends in
      incidence can only be partially explained by the HIV epidemic. In 1992, an
      international workshop sponsored by the United States National Cancer Institute
      concluded that there was an "emerging epidemic" of NHL and emphasized the need to
      investigate the factors responsible for the increasing incidence of this disease.
      Over the past two decades, numerous epidemiological studies have examined the
      risk factors for NHL, particularly for putative environmental and lifestyle risk
      factors, and international consortia have been established in order to
      investigate rare exposures and NHL subtype-specific associations. While few
      consistent risk factors for NHL aside from immunosuppression and certain
      infectious agents have emerged, suggestive associations with several lifestyle
      and environmental factors have been reported in epidemiologic studies. Further,
      increasing evidence has suggested that the effects of these and other exposures
      may be limited to or stronger for particular NHL subtypes. This paper examines
      the progress that has been made over the last twenty years in elucidating the
      etiology of NHL, with a primary emphasis on lifestyle factors and environmental
      exposures.

PMID- 23008720
TI  - Impact of universal vaccination against hepatitis B: the italian model.

PMID- 23008717
TI  - Crosstalk between Platelets and the Immune System: Old Systems with New
      Discoveries.
AB  - Platelets are small anucleate cells circulating in the blood. It has been
      recognized for more than 100 years that platelet adhesion and aggregation at the
      site of vascular injury are critical events in hemostasis and thrombosis;
      however, recent studies demonstrated that, in addition to these classic roles,
      platelets also have important functions in inflammation and the immune response.
      Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin,
      CD40L, IL-1beta, etc.), which support leukocyte trafficking, modulate
      immunoglobulin class switch, and germinal center formation. Platelets express
      several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9,
      which may potentially link innate immunity with thrombosis. Interestingly,
      platelets also contain multiple anti-inflammatory molecules and cytokines (e.g.,
      transforming growth factor-beta and thrombospondin-1). Emerging evidence also
      suggests that platelets are involved in lymphatic vessel development by directly
      interacting with lymphatic endothelial cells through C-type lectin-like receptor
      2. Besides the active contributions of platelets to the immune system, platelets
      are passively targeted in several immune-mediated diseases, such as autoimmune
      thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal
      alloimmune thrombocytopenia. These data suggest that platelets are important
      immune cells and may contribute to innate and adaptive immunity under both
      physiological and pathological conditions.

PMID- 23008721
TI  - Serum hepatitis B surface antigen levels and their utility as a predictor of
      sustained virological response after antiviral treatment.

PMID- 23008722
TI  - Treatment Response and Tolerability of Pegylated Interferon-alpha Plus Ribavirin
      Combination Therapy in elderly Patients (>= 65 years) With Chronic Hepatitis C in
      Korea.
AB  - BACKGROUND: The prevalence of hepatitis C virus (HCV) infections in elderly
      patients has been increasing in a number of countries. A few reports concerning
      pegylated interferon-alpha (PEG-IFN-alpha)-based combination treatment in elderly
      chronic hepatitis C (CHC) patients have been published, with slightly different
      treatment outcomes. OBJECTIVES: We investigated the treatment response and safety
      of PEG-IFN-alpha plus ribavirin combination therapy in elderly patients with CHC.
      PATIENTS AND METHODS: Among a total of 181 treatment-naive CHC patients (60
      patients with genotype 1, 121 patients with genotype 2 or 3), 38 were aged >= 65
      years (defined as the elderly group) and 143 were aged < 65 years (defined as the
      non-elderly group). RESULTS: The overall sustained virologic response (SVR) was
      lower in the elderly group than in the non-elderly group, but it was not
      significantly different (65.8 % vs. 76.2 %, P = 0.15). In a subgroup analysis,
      among patients with genotype 1, the elderly group had a significantly lower SVR
      rate than the non-elderly group (30.8 % vs. 66.0 %, P = 0.03). However, the SVR
      rate in patients with HCV genotype 2 or 3 was comparable between the two groups
      (84.0 % vs. 81.3 %, P = 0.85). HCV genotype was significantly associated with SVR
      in the elderly patients (genotype 1 vs. 2 or 3, odds ratio: 0.18, 95% confidence
      interval: 0.000-0.869, P = 0.03). The incidence of premature discontinuation of
      treatment (21.1 % vs. 9.1 %, P = 0.05) and dose modification (52.6 % vs. 31.5 %;
      P = 0.02) due mainly to adverse events or laboratory abnormalities, were higher
      in the elderly group than in the non-elderly group. CONCLUSIONS: PEG-IFN-alpha
      plus ribavirin combination therapy might be considered for elderly CHC patients,
      especially for genotype 2 or 3, with vigilant monitoring of adverse events.

PMID- 23008723
TI  - Phylogenetic analysis of torque teno virus in hepatitis C virus infected patients
      in shiraz.
AB  - BACKGROUND: Torque teno virus (TTV) was the first human Circoviridae detected in
      a Japanese patient with unknown hepatitis in 1997. Subsequently, several studies
      performed to evaluate different aspects of Torque teno virus pathogenesis.
      OBJECTIVES: The present study aimed to determine dominant genotype of Torque teno
      virus in chronic hepatitis disease using 5?-UTR sequence among patients infected
      by hepatitis C virus in Shiraz - Iran. PATIENTS AND METHODS: The study conducted
      in 240 patients with chronic hepatitis C from Prof. Alborzi Clinical Microbiology
      Research Center. The presence of Torque teno virus DNA and its genotype in plasma
      was assessed by nested polymerase chain reaction using two primer sets for 5?-UTR
      and N22 regions. Phylogenetic analysis was performed based on 5?-UTR region.
      RESULTS: DNA of Torque teno virus was detected in 220 out of 240 (92 %) patients
      with chronic hepatitis C by the use of 5?-UTR primer based PCR method and in 12
      out of 240 (5%) by the use of N22 primer. Based on phylogenetic analysis it was
      shown that the Dominant genotype in this study was 11. Genotypes 1, 3, 17, and 22
      were also detected. Some sequences could not be classified to a specific
      genotype. CONCLUSIONS: The prevalence of Torque teno virus DNA in patients with
      chronic hepatitis C disease by the use of 5?-UTR primer appeared to be higher
      compared to that revealed by N22 primer. We observed five genotypes among
      hepatitis C chronic patients in our study.

PMID- 23008724
TI  - Prevalence and Risk Factors of HIV, Syphilis, Hepatitis B and C Among Female
      Prisoners in Isfahan, Iran.
AB  - BACKGROUND: Female prisoners are at risk of acquiring sexually transmitted
      infections (STIs). There has been no previous study regarding the epidemiological
      status of STIs among female prisoners in Isfahan, central Iran. OBJECTIVES: The
      aim of this study was to investigate the prevalence and risk factors of the
      aforementioned infections among women incarcerated in the central prison,
      Isfahan, to determine appropriate prevention measures. PATIENTS AND METHODS: In a
      cross-sectional study, all of the 163 women incarcerated in the central prison,
      Isfahan in 2009, were voluntarily enrolled by the census method. After completing
      a checklist consisting of demographic, social, and risk factors, a 5ml blood
      sample was taken from each individual. The sera were analyzed for markers of the
      hepatitis B virus (HBV; HBsAg, HBsAb, HBcAb), hepatitis C virus (HCV; HCV
      antibodies), human immunodeficiency virus (HIV; HIV antibodies), and syphilis
      (RPR). Confirmatory tests were performed on HCV antibody-positive cases. RESULTS:
      The mean age of the participants in the study was 34.54 +/- 11.2 years old, 94.3%
      of these women were Iranian, and many of them had only a primary level of
      education. The prevalence of HBsAg, HBcAb, HBsAb, and HCV antibodies were; 1.2%,
      7.4%, 12.9% and 7.4% respectively. No positive RPR or HIV antibodies were
      detected. CONCLUSIONS: A significant relationship was seen between the HCV
      antibody, drug injection and illegal sex in the women, and also between HBc-Ab
      and drug injection. Regular screening, educational programs, and facilitation of
      access to suitable treatment care should be widely implemented in the prison
      population. Testing for immunity against HBV should be considered on admission,
      and afterwards vaccination of all prisoners and an appropriate preventative
      approach should be applied.

PMID- 23008725
TI  - Cytologic comparison between malignant and regenerative nodules in the background
      of cirrhosis.
AB  - BACKGROUND: Incidence of hepatocellular carcinoma has been increased as the sixth
      most common cancer in the world. Improvement in imaging techniques has decreased
      the need for tissue confirmation in diagnosis of hepatocellular carcinoma (HCC).
      Meanwhile, false negative and positive cases are present. Fine needle aspiration
      (FNA) biopsy can be helpful to identify well-differentiated HCCs with low risk of
      vascular invasion and better prognosis following transplantation. OBJECTIVES: We
      conducted this study to find useful criteria for cytological differential
      diagnosis between nodules of well differentiated hepatocellular in the background
      of cirrhosis and pure cirrhotic regenerative nodules in cytology smears.
      MATERIALS AND METHODS: 140 fine needle aspirations (FNA) of fresh cirrhotic
      hepatectomy specimens were studied (100 pure regenerative nodules and 40 HCC
      nodules). All slides were reviewed by two expert pathologists. The most useful
      criteria were selected and evaluated in 560 cytology smears stained by Pap and
      Wright methods. RESULTS: None of the smears from cirrhotic patients showed
      mitosis, transgressing endothelium, eccentric nuclei, and scant cytoplasm, but
      thick nuclear membrane, spindle cells and abundant, thick and monotonous
      cytoplasm were found in many cases with cirrhosis. Large nucleoli (2 %), multiple
      nucleoli (6 %), increased N/C ratio (4 %), and broad cores (2 %) were found very
      rarely in the smears of regenerative nodules, but they were present in 50 %, 72.5
      %, 87 %, and 77.5 % of HCC nodules, respectively. CONCLUSIONS: Combination of
      cytologic criteria can be helpful for differential diagnosis between HCC and
      regenerative nodules.

PMID- 23008726
TI  - Plasma Hepatitis C Virus Viral Load Among Hepatitis C Virus Mono-Infected and
      HCV/HIV Co-Infected Individuals in Yunnan Province,China.
AB  - BACKGROUND: Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co
      infection has become a serious public health problem especially in high risk
      groups such as injection drug users in China. However, the impact of HIV
      infection and antiretroviral therapy (ART) on HCV viral load which is usually
      regarded as a predictor of liver disease progress had not been well studied in
      this country. OBJECTIVES: To explore correlations of HIV co-infection and ART
      with plasma HCV load among HCV-infected patients in an ethnic minority area in
      Yunnan Province, China. PATIENTS AND METHODS: HCV/HIV co-infected patients and
      HCV mono-infected controls were examined and compared for plasma HCV RNA and
      related risk factors. RESULTS: A total of 145 HCV/HIV co-infected patients and 25
      HCV mono-infected controls were studied. The majority of the participants were
      male, belonged to an ethnic minority and were younger than 45 years old. HCV
      viral suppression rate with undetectable plasma HCV viral load was 28.3% in the
      HCV/HIV co-infected patients, 36% among HCV mono-infected controls and 29.4%
      overall. ART-prescribed HCV/HIV co-infected patients had significantly higher HCV
      viral loads (IQR: (3.80-6.44)*log(10) copies ml-1) than those naive to ART (IQR:
      (undetectable-6.41)*log(10) copies ml-1) and HCV mono-infected patients (IQR:
      (undetectable-5.44)*log(10) copies ml-1). Men, from the Dai minority and those
      with more than six years education, were also shown to have a higher plasma HCV
      viral load,according to multiple logistic regression analysis. CONCLUSIONS: ART
      potentially increases the plasma HCV viral load among HCV/HIV coinfected patients
      in an ethnic minority area in China. Future large scale prospective cohort
      studies are needed to address the controversy associated between HIV co-infection
      and the natural history of HCV.

PMID- 23008727
TI  - Epidemiology of viral hepatitis B and C infections in ibb city, yemen.
AB  - BACKGROUND: The global epidemic of hepatitis B and hepatitis C is a serious
      publichealth problem. Chronic hepatitis B and hepatitis C are among the leading
      causes of preventable death worldwide. World Health Organization (WHO) estimates
      that up to two billion people in the world have been infected with HBV; about 350
      million people live with chronic HBV infection, and about 600,000 people die from
      HBV- related liver disease or HCC each year. The endemicity of infection is
      considered high in Yemen. Data for prevalence of HBsAg and HCV antibodies in Ibb
      city in Yemen is rare and inadequate. OBJECTIVES: The study was undertaken to
      study the epidemiology and prevalence of viral hepatitis (HBV) and (HCV) in Ibb
      city, Yemen. PATIENTS AND METHODS: 554 pre-designed questionnaires and sera
      samples were collected in July 2010. Sera were tested for HBsAg and HCV
      antibodies by ELISA quantitative technique. Each individual's data were collected
      in a pre-designed questionnaire. RESULTS: The prevalence of HBV in Ibb city was
      1.81 %, whereas, the prevalence of HCV was 1.99 %. CONCLUSIONS: This study
      revealed low level risk of hepatitis B virus and hepatitis C virus infections.
      Inadequate information on the prevalence and risk determinants of viral hepatitis
      among the different population groups in Yemen are responsible about morbidity
      and mortality of HBV and HCV in Ibb city, Yemen.

PMID- 23008728
TI  - Viral Hepatitis and HIV Infection in Hemodialysis Patients.

PMID- 23008729
TI  - Decreasing High Failure Rate of Vaccinations in Patients With Chronic Kidney
      Disease; not Just a Matter of Quantity.

PMID- 23008730
TI  - Occult hepatitis B infection in different high risk patients.

PMID- 23008731
TI  - The effect of specific immunotherapy on natural killer T cells in peripheral
      blood of house dust mite-sensitized children with asthma.
AB  - To investigate the effects of specific immunotherapy on the NKT cells in
      peripheral blood and the ability of NKT cells to proliferate in response to alpha
      galactosylceramide (alpha-GalCer) in house-dust-mite- (HDM-) sensitized asthma
      children, peripheral blood mononuclear cells were isolated from 42 asthmatic
      children, of whom 24 were on specific immunotherapy (SIT) for more than a year
      and 20 were healthy. Compared with control group, the ratio of peripheral blood
      NKT and CD4(+)NKT cells was significantly decreased (P < 0.01) and was elevated
      in SIT asthma group (P < 0.05), respectively, but it was still less than the
      normal control group (P < 0.01). The level of IL-4 in serum secreted by NKT cells
      in asthma group was significantly higher than that of control group (P < 0.01),
      particularly apparent after 72 hours. The level of IL-4 in SIT group decreased
      significantly (P < 0.01). The level of IL-10 in serum secreted by NKT cells in
      asthma group was decreased significantly than that of the control group (P <
      0.01) especially in 48 hours, while that of SIT group was increased significantly
      (P < 0.01). These results suggest that the pathogenesis of asthma may be related
      to the ratio and dysfunction of NKT and CD4(+)NKT cells.

PMID- 23008732
TI  - The impact of osteopontin gene variations on multiple sclerosis development and
      progression.
AB  - Osteopontin is a proinflammatory molecule, modulating TH1 and TH17 responses.
      Several reports suggest its involvement in multiple sclerosis (MS) pathogenesis.
      We previously reported that OPN gene variations at the 3' end are a predisposing
      factor for MS development and evolution. In this paper, we extended our analysis
      to a gene variation at the 5' end on the -156G > GG single nucleotide
      polymorphism (SNP) and replicated our previous findings at the 3' end on the
      +1239A > C SNP. We found that only +1239A > C SNP displayed a statistically
      significant association with MS development, but both +1239A > C and -156G > GG
      had an influence on MS progression, since patients homozygous for both +1239A and
      -156GG alleles displayed slower progression of disability and slower switch to
      secondary progression than those carrying +1239C and/or -156G and those
      homozygous for +1239A only. Moreover, patients homozygous for +1239A also
      displayed a significantly lower relapse rate than those carrying +1239C, which is
      in line with the established role of OPN in MS relapses.

PMID- 23008733
TI  - Lyme borreliosis: from pathogenesis to diagnosis and treatment.

PMID- 23008734
TI  - Immune development and intestinal microbiota in celiac disease.
AB  - Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat
      gluten and similar proteins of barley and rye in genetically susceptible
      individuals. The etiology of this disorder is complex, involving both
      environmental and genetic factors. The major genetic risk factor for CD is
      represented by HLA-DQ genes, which account for approximately 40% of the genetic
      risk; however, only a small percentage of carriers develop the disease. Gluten is
      the main environmental factor responsible for the signs and symptoms of the
      disease, but exposure to gluten does not fully explain the manifestation of CD.
      Epidemiological and clinical data suggest that environmental factors other than
      gluten might play a role in disease development, including early feeding
      practices (e.g., breast milk versus formula and duration of breastfeeding),
      infections, and alterations in the intestinal microbiota composition. Herein, we
      review what is known about the influence of dietary factors, exposure to
      infectious agents, and intestinal microbiota composition, particularly in early
      life, on the risk of developing CD, as well as the possible dietary strategies to
      induce or increase gluten tolerance.

PMID- 23008735
TI  - Recent understanding on diagnosis and management of central nervous system
      vasculitis in children.
AB  - Central nervous system vasculitides in children may develop as a primary
      condition or secondary to an underlying systemic disease. Many vasculitides
      affect both adults and children, while some others occur almost exclusively in
      childhood. Patients usually present with systemic symptoms with single or
      multiorgan dysfunction. The involvement of central nervous system in childhood is
      not frequent and it occurs more often as a feature of subtypes like childhood
      polyarteritis nodosa, Kawasaki disease, Henoch Schonlein purpura, and Bechet
      disease. Primary angiitis of the central nervous system of childhood is a
      reversible cause of severe neurological impairment, including acute ischemic
      stroke, intractable seizures, and cognitive decline. The first line therapy of
      CNS vasculitides is mainly based on corticosteroids and immunosuppressor drugs.
      Other strategies include plasmapheresis, immunoglobulins, and biologic drugs.
      This paper discusses on current understanding of most frequent primary and
      secondary central nervous system vasculitides in children including a tailored
      diagnostic approach and new evidence regarding treatment.

PMID- 23008736
TI  - Immunological evaluation and comparison of different EV71 vaccine candidates.
AB  - Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are major causative agents
      of hand, foot, and mouth diseases (HFMDs), and EV71 is now recognized as an
      emerging neurotropic virus in Asia. Effective medications and/or prophylactic
      vaccines against HFMD are not available. The current results from mouse
      immunogenicity studies using in-house standardized RD cell virus neutralization
      assays indicate that (1) VP1 peptide (residues 211-225) formulated with Freund's
      adjuvant (CFA/IFA) elicited low virus neutralizing antibody response (1/32
      titer); (2) recombinant virus-like particles produced from baculovirus formulated
      with CFA/IFA could elicit good virus neutralization titer (1/160); (3) individual
      recombinant EV71 antigens (VP1, VP2, and VP3) formulated with CFA/IFA, only VP1
      elicited antibody response with 1/128 virus neutralization titer; and (4) the
      formalin-inactivated EV71 formulated in alum elicited antibodies that cross
      neutralized different EV71 genotypes (1/640), but failed to neutralize CVA16. In
      contrast, rabbits antisera could cross-neutralize strongly against different
      genotypes of EV71 but weakly against CVA16, with average titers 1/6400 and 1/32,
      respectively. The VP1 amino acid sequence dissimilarity between CVA16 and EV71
      could partially explain why mouse antibodies failed to cross-neutralize CVA16.
      Therefore, the best formulation for producing cost-effective HFMD vaccine is a
      combination of formalin-inactivated EV71 and CAV16 virions.

PMID- 23008737
TI  - Biosynthesis and immobilization of biofunctional allophycocyanin.
AB  - The holo-allophycocyanin-alpha subunit, which has various reported
      pharmacological uses, was biosynthesized with both Strep-II-tag and His-tag at
      the N-terminal in Escherichia coli. The streptavidin-binding ability resulting
      from the Strep II-tag was confirmed by Western blot. Additionally, the metal
      chelating ability deriving from the His-tag not only facilitated its purification
      by immobilized metal-ion affinity chromatography but also promoted its
      immobilization on Zn (II)-decorated silica-coated magnetic nanoparticles. The
      holo-allophycocyanin-alpha subunit with streptavidin-binding ability was thereby
      immobilized on magnetic nanoparticles. Magnetic nanoparticles are promising as
      drug delivery vehicles for targeting and locating at tumors. Thus, based on
      genetic engineering and nanotechnology, we provide a potential strategy to
      facilitate the biomodification and targeted delivery of pharmacological proteins.

PMID- 23008738
TI  - Effects of yoga on mental and physical health: a short summary of reviews.
AB  - This report summarizes the current evidence on the effects of yoga interventions
      on various components of mental and physical health, by focussing on the evidence
      described in review articles. Collectively, these reviews suggest a number of
      areas where yoga may well be beneficial, but more research is required for
      virtually all of them to firmly establish such benefits. The heterogeneity among
      interventions and conditions studied has hampered the use of meta-analysis as an
      appropriate tool for summarizing the current literature. Nevertheless, there are
      some meta-analyses which indicate beneficial effects of yoga interventions, and
      there are several randomized clinical trials (RCT's) of relatively high quality
      indicating beneficial effects of yoga for pain-associated disability and mental
      health. Yoga may well be effective as a supportive adjunct to mitigate some
      medical conditions, but not yet a proven stand-alone, curative treatment. Larger
      scale and more rigorous research with higher methodological quality and adequate
      control interventions is highly encouraged because yoga may have potential to be
      implemented as a beneficial supportive/adjunct treatment that is relatively cost
      effective, may be practiced at least in part as a self-care behavioral treatment,
      provides a life-long behavioural skill, enhances self-efficacy and self
      confidence and is often associated with additional positive side effects.

PMID- 23008739
TI  - Effect of Treatment with Cyanidin-3-O-beta-D-Glucoside on Rat
      Ischemic/Reperfusion Brain Damage.
AB  - This study investigated the effect of cyanidin-3-O-beta-glucoside on an
      experimental model of partial/transient cerebral ischemia in the rats in order to
      verify the effectiveness of both pre- and posttreatments. Cyanidin-3-O-beta
      glucoside-pretreated rats were injected with 10 mg/Kg i.p. 1 h before the
      induction of cerebral ischemia; in posttreated rats, the same dosage was injected
      during reperfusion (30 min after restoring blood flow). Cerebral ischemia was
      induced by bilateral clamping of common carotid arteries for 20 min. Ischemic
      rats were sacrificed immediately after 20 min ischemia; postischemic reperfused
      animals were sacrificed after 3 or 24 h of restoring blood flow. Results showed
      that treatment with cyanidin increased the levels of nonproteic thiol groups
      after 24 h of postischemic reperfusion, significantly reduced the lipid
      hydroperoxides, and increased the expression of heme oxygenase and gamma-glutamyl
      cysteine synthase; a significant reduction in the expression of neuronal and
      inducible nitric oxide synthases and the equally significant increase in the
      endothelial isoform were observed. Significant modifications were also detected
      in enzymes involved in metabolism of endogenous inhibitors of nitric oxide. Most
      of the effects were observed with both pre- and posttreatments with cyanidin-3-O
      beta-glucoside suggesting a role of anthocyanin in both prevention and treatment
      of postischemic reperfusion brain damage.

PMID- 23008740
TI  - Chinese herbal medicine paratherapy for Parkinson's disease: a meta-analysis of
      19 randomized controlled trials.
AB  - Parkinson's disease (PD) is a common and debilitating neurodegenerative disorder
      that needs long-term levodopa administration and can result in progressive
      deterioration of body functions, daily activities and participation. The
      objective of this meta-analysis evaluates the clinical efficacy and safety of
      Chinese herbal medicine (CHM) as an adjunct therapy for PD patients.
      Methodological issues include a systematic literature search between 1950 and
      April 2011 to identify randomized trials involving CHM adjuvant therapy versus
      western conventional treatment. The outcome measures assessed were the reduction
      in scores of Unified Parkinson's Disease Rating Scale (UPDRS) and adverse
      effects. 19 trials involving 1371 participants were included in the meta
      analysis. As compared to western conventional treatment, CHM adjuvant therapy
      resulted in greater improvement in UPDRS I, II, III, IV scores, and UPDRS I-IV
      total scores (P < 0.001). Adverse effects were reported in 9 studies. The side
      effects in CHM adjuvant therapy group were generally less than or lighter than
      the conventional treatment group. In conclusion, CHM adjuvant therapy may
      potentially alleviate symptoms of PD and generally appeared to be safe and well
      tolerated by PD patients. However, well-designed, randomized, placebo-controlled
      clinical trials are still needed due to the generally low methodological quality
      of the included studies.

PMID- 23008741
TI  - Inhibition of Advanced Glycation End-Product Formation by Origanum majorana L. In
      Vitro and in Streptozotocin-Induced Diabetic Rats.
AB  - The development of AGE inhibitors is considered to have therapeutic potential in
      patients with diabetes diseases. The aim of the present study was investigate the
      effect of methanolic extract of the leaves of Origanum majorana (OM) used as
      spice in many countries on AGEs formation. In vitro studies indicated a
      significant inhibitory effects on the formation of AGEs. Their antiglycation
      activities were not only brought about by their antioxidant activities but also
      related to their trapping abilities of reactive carbonyl species such as
      methylglyoxal, an intermediate reactive carbonyl of AGE formation. The results
      demonstrate that OM have significant effects on in vitro AGE formation, and the
      glycation inhibitory activity was more effectively than those obtained using as
      standard antiglycation agent aminoguanidine. OM is a potent agent for protecting
      LDL against oxidation and glycation. Treatment of streptozotocin-diabetic mice
      with OM and glibenclamide for 28 days had beneficial effects on renal metabolic
      abnormalities including glucose level and AGEs formation. Diabetic mice showed
      increase in tail tendon collagen, glycated collagen linked fluorescence and
      reduction in pepsin digestion. Treatment with OM improved these parameters when
      compared to diabetic control and glibenclamide.

PMID- 23008742
TI  - Polygonum cuspidatum Extract Induces Anoikis in Hepatocarcinoma Cells Associated
      with Generation of Reactive Oxygen Species and Downregulation of Focal Adhesion
      Kinase.
AB  - Anoikis has been recognized as a potential target for anticancer therapy.
      Polygonum cuspidatum (Huzhang) is a frequently used Chinese herb in
      hepatocarcinoma. In present study, we evaluated the effects of Polygonum
      cuspidatum extract (PCE) in hepatocarcinoma cells in suspension. The results
      showed that PCE inhibited the proliferation of hepatocarcinoma cells in
      suspension in a dose- and time-dependent manner. PCE also inhibited anchorage
      independent growth of hepatocarcinoma cells in soft agar. PCE induced anoikis in
      human hepatocarcinoma Bel-7402 cells accompanied by caspase-3 and caspase-9
      activation and poly(ADP-ribose) polymerase cleavage, which was completely
      abrogated by a pan caspase inhibitor, Z-VAD-FMK. In addition, PCE treatment
      induced intracellular reactive oxygen species (ROS) production in Bel-7402 cells.
      NAC, an ROS scavenger, partially attenuated PCE-induced anoikis and activation of
      caspase-3 and caspase-9. Furthermore, PCE inhibited expression of focal adhesion
      kinase (FAK) in Bel-7402 cells. Overexpression of FAK partially abrogated PCE
      induced anoikis. These data suggest that PCE may inhibit suspension growth and
      induce caspase-mediated anoikis in hepatocarcinoma cells and may relate to ROS
      generation and FAK downregulation. The present study provides new insight into
      the application of Chinese herb for hepatocarcinoma treatment.

PMID- 23008743
TI  - Fisetin Inhibits Osteoclast Differentiation via Downregulation of p38 and c-Fos
      NFATc1 Signaling Pathways.
AB  - The prevention or therapeutic treatment of loss of bone mass is an important
      means of improving the quality of life for patients with disorders related to
      osteoclast-mediated bone loss. Fisetin, a flavonoid dietary ingredient found in
      the smoke tree (Continus coggygria), exhibits various biological activities, but
      its effect on osteoclast differentiation is unknown. In this study, fisetin dose
      dependently inhibited the RANKL-induced osteoclast differentiation with
      downregulation of the activity or expression of p38, c-Fos, and NFATc1 signaling
      molecules. The p38/c-Fos/NFATc1-regulated expression of genes required for cell
      fusion and bone resorption, such as DC-STAMP and cathepsin K, was also inhibited
      by fisetin. Considering the rescue of fisetin's inhibitory action by NFATc1 over
      expression, the cascade of p38-c-Fos-NFATc1 could be strongly involved in the
      inhibitory effect of fisetin on osteoclast differentiation. Furthermore, fisetin
      inhibited the bone-resorbing activity of mature osteoclasts. In conclusion,
      fisetin may be of use in the treatment of osteoclast-related disorders, including
      osteoporosis.

PMID- 23008744
TI  - Antidepressant-like effects of shuyusan in rats exposed to chronic stress:
      effects on hypothalamic-pituitary-adrenal function.
AB  - This study was to investigate antidepressant activities of Shuyusan (a Chinese
      herb), using a rats model of depression induced by unpredictable chronic mild
      stress (UCMS). The administration groups were treated with Shuyusan decoction for
      3 weeks and compared with fluoxetine treatment. In order to understand the
      potential antidepressant-like activities of Shuyusan, tail suspension test (TST)
      and forced swimming test (FST) were used as behavioral despair study. The level
      of corticotropin-releasing factor (CRH), adrenocorticotropic hormone (ACTH),
      corticosterone (CORT) and hippocampus glucocorticoid receptor expression were
      examined. After modeling, there was a significant prolongation of immobility time
      in administration groups with the TST and FST. High-dose Shuyusan could reduce
      the immobility time measured with the TST and FST. The immobility time in high
      dose herbs group and fluoxetine group was increased significantly compared with
      the model group. After 3 weeks herbs fed, the serum contents level of CRH, ACTH,
      and CORT in high-dose herb group was significantly decreased compared to the
      model group. The result indicated that Shuyusan had antidepressant activity
      effects on UCMS model rats. The potential antidepressant effect may be related to
      decreasing glucocorticoid levels activity, regulating the function of HPA axis,
      and inhibiting glucocorticoid receptor expression in hippocampus.

PMID- 23008745
TI  - Endothelium/Nitric Oxide Mediates the Vasorelaxant and Antihypertensive Effects
      of the Aqueous Extract from the Stem Bark of Mammea africana Sabine (Guttiferae).
AB  - This study evaluates the vasorelaxant and antihypertensive effects of the aqueous
      extract from the stem bark of M. africana (AEMA). AEMA was tested in vitro on
      intact or endothelium-denuded rats' aorta rings precontracted with KCl or
      norepinephrine in absence or in presence of L-NAME or glibenclamide. The effect
      of a single concentration (300 MUg/mL) of AEMA was also examined on the
      concentration-response curve of KCl. In vivo, the antihypertensive effects of
      AEMA (200 mg/kg/day) were evaluated in male Wistar rats treated with L-NAME (40
      mg/kg/day) for 4 weeks. AEMA relaxed aorta rings precontracted with NE or KCl
      with respective EC50 values of 0.36 MUg/mL and 197.60 MUg/mL. The destruction of
      endothelium or pretreatment of aorta rings with L-NAME shifted the EC50 of AEMA
      from 0.36 MUg/mL to 40.65 MUg/mL and 20.20 MUg/mL, respectively. The vasorelaxant
      activity of M. africana was significantly inhibited in presence of glibenclamide.
      AEMA also significantly inhibited the concentration-response curve of KCl.
      Administered orally, AEMA induced acute and chronic antihypertensive effects and
      normalized renal NO level. These results show that the vasorelaxant activity of
      AEMA might be mediated by the activation of the NO-cGMP-ATP-dependent potassium
      channels pathway and might predominantly account for its antihypertensive effect.

PMID- 23008746
TI  - Awareness and knowledge of cervical cancer and its prevention among the nursing
      staff of a tertiary health institute in Ahmedabad, Gujarat, India.
AB  - BACKGROUND: Carcinoma of the cervix is the second most common cancer in women
      worldwide, while it is the commonest cancer among Indian women. Awareness
      regarding cervical cancer and its prevention is quite low amongst Indian women.
      The Pap test is a simple and cost effective technique for early diagnosis of
      cervical cancer. It is necessary to make nursing staff aware of cervical cancer,
      so that they can impart knowledge regarding cervical cancer and its prevention to
      the general public. AIMS AND OBJECTIVES: (1) To assess the knowledge level
      regarding symptoms, risk factors, prevention and screening of cervical carcinoma
      among nursing staff. (2) To find out the behaviour of respondents regarding
      prevention and screening of cervical carcinoma. MATERIALS AND METHODS: A cross
      sectional interview-based survey regarding knowledge levels about cervical
      carcinoma was conducted among the nursing staff from one of the tertiary health
      institutes of Ahmedabad, India. A structured questionnaire with multiple choices
      was used for data collection. Provision for open-ended responses was also made in
      the questionnaire. Department-wise stratification was carried out, and thereafter
      15% of the total nursing staff from all departments were selected randomly so as
      to include a total of 100 nurses in the current study. Data entry was done in
      Microsoft Excel. SPSS statistical software was used to generate statistical
      parameters like proportion, mean, standard deviation, etc. The Z test was used as
      a test of significance, and a P value of <0.05 was considered as the level of
      significance.

PMID- 23008747
TI  - Correlation between high-risk pregnancy and developmental delay in children aged
      4-60 months.
AB  - BACKGROUND: The future development of children is considered more than ever now
      due to the advances in medical knowledge and thus the increase in survival rates
      of high-risk infants. This study investigated the correlation between high-risk
      pregnancy and developmental delay in children aged 4-60 months. METHODS: This
      descriptive study was conducted on 401 mothers and their children (4-60 months)
      who visited health service centers affiliated to Isfahan University of Medical
      Sciences, Iran, in 2011. Sampling was carried out in several stages, and the Ages
      and Stage Questionnaire was completed by the participants. Data were analyzed
      with SPSS 18 software and independent t-test; Mann-Whitney and logistic
      regression tests were used. RESULTS: The average age of children in the low-risk
      pregnancy group was 22+/-16 months, and that in the high-risk pregnancy group was
      18.9+/-14.8 months. The majority of children were female (53.1%). The prevalence
      of high-risk pregnancies was 80.5%, and the prevalence of developmental delay was
      18.7%. Multiple pregnancies, low birth weight, habitual abortions, maternal
      medical disorders in pregnancy, and gestational diabetes had significant
      correlations with developmental delay in children (P<0.04). In the logistic
      model, male gender, low birth weight, family marriage, and maternal medical
      disorders during pregnancy showed significant correlations with developmental
      delay in children (P<0.05). Additionally, abnormal body mass index (BMI) and
      social and economic status showed probability values close to the significance
      level (P = 0.05), whereas other high-risk pregnancy variables had no correlation
      with developmental delay in children. A correlation between high-risk pregnancy
      and developmental delay (P = 0.002) and fine motor delay was observed (P = 0.02),
      but no correlation was observed between high-risk pregnancy and other
      developmental domains. CONCLUSION: This study showed that some high-risk
      pregnancy variables had a significant correlation with developmental delay.
      Moreover, a significant correlation was observed between high-risk pregnancy and
      fine motor developmental delay.

PMID- 23008748
TI  - The therapeutic potential of cannabis and cannabinoids.
AB  - BACKGROUND: Cannabis-based medications have been a topic of intense study since
      the endogenous cannabinoid system was discovered two decades ago. In 2011, for
      the first time, a cannabis extract was approved for clinical use in Germany.
      METHODS: Selective literature review. RESULTS: Cannabis-based medications exert
      their effects mainly through the activation of cannabinoid receptors (CB1 and
      CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant
      preparations for various indications have been conducted since 1975. The findings
      of these trials have led to the approval of cannabis-based medicines (dronabinol,
      nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany,
      a cannabis extract was approved in 2011 for the treatment of moderate to severe
      refractory spasticity in multiple sclerosis. It is commonly used off label for
      the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply
      for government permission to buy medicinal cannabis flowers for self-treatment
      under medical supervision. The most common side effects of cannabinoids are
      tiredness and dizziness (in more than 10% of patients), psychological effects,
      and dry mouth. Tolerance to these side effects nearly always develops within a
      short time. Withdrawal symptoms are hardly ever a problem in the therapeutic
      setting. CONCLUSION: There is now clear evidence that cannabinoids are useful for
      the treatment of various medical conditions.

PMID- 23008749
TI  - Euthyroid goiter with and without nodules--diagnosis and treatment.
AB  - BACKGROUND: Thyroid enlargement and thyroid nodules are common in the general
      population. This review concerns their proper diagnostic assessment and
      treatment. METHODS: We selectively reviewed the literature from 1990 to 2012 and
      evaluated original articles and reviews retrieved from the PubMed database, as
      well as the recommendations of the following specialty societies: the German
      Societies of Endocrinology and Nuclear Medicine (Deutsche Gesellschaft fur
      Endokrinologie, Deutsche Gesellschaft fur Nuklearmedizin), the German Working
      Group for Endocrine Surgery (Chirurgische Arbeitsgemeinschaft Endokrinologie,
      CAEK), the European Thyroid Association, and the American Thyroid Association.
      RESULTS: There have been very few randomized trials concerning the diagnosis and
      treatment of goiter. Nodular goiter can be managed by watchful waiting, drug
      treatment (initially with levothyroxine and iodide), radioactive iodine therapy,
      or surgery. CONCLUSION: Many patients with nodules need no treatment at all.
      Treatment is indicated, however, if the patient is symptomatic and/or has an
      autonomously functioning ("hot") nodule, or if cancer is suspected. Potentially
      cancerous nodules must be operated on. If euthyroid nodular goiter is to be
      treated with the main goal of size reduction, either surgery or radioactive
      iodine therapy can be used. Drug treatment is an option for small nodules or
      goiters, but iatrogenic hyperthyroidism must be avoided at all costs. The type of
      follow-up that is required depends on the chosen treatment.

PMID- 23008750
TI  - Why large porphyry Cu deposits like high Sr/Y magmas?
AB  - Porphyry systems supply most copper and significant gold to our economy. Recent
      studies indicate that they are frequently associated with high Sr/Y magmatic
      rocks, but the meaning of this association remains elusive. Understanding the
      association between high Sr/Y magmatic rocks and porphyry-type deposits is
      essential to develop genetic models that can be used for exploration purposes.
      Here we present results on a Pleistocene volcano of Ecuador that highlight the
      behaviour of copper in magmas with variable (but generally high) Sr/Y values. We
      provide indirect evidence for Cu partitioning into a fluid phase exsolved at
      depths of ~15 km from high Sr/Y (>70) andesitic magmas before sulphide
      saturation. This lends support to the hypothesis that large amounts of Cu- and S
      bearing fluids can be accumulated into and released from a long-lived high Sr/Y
      deep andesitic reservoir to a shallower magmatic-hydrothermal system with the
      potential of generating large porphyry-type deposits.

PMID- 23008751
TI  - Social and strategic imitation: the way to consensus.
AB  - Humans do not always make rational choices, a fact that experimental economics is
      putting on solid grounds. The social context plays an important role in
      determining our actions, and often we imitate friends or acquaintances without
      any strategic consideration. We explore here the interplay between strategic and
      social imitative behavior in a coordination problem on a social network. We
      observe that for interactions on 1D and 2D lattices any amount of social
      imitation prevents the freezing of the network in domains with different
      conventions, thus leading to global consensus. For interactions on complex
      networks, the interplay of social and strategic imitation also drives the system
      towards global consensus while neither dynamics alone does. We find an optimum
      value for the combination of imitative behaviors to reach consensus in a minimum
      time, and two different dynamical regimes to approach it: exponential when social
      imitation predominates, power-law when strategic considerations prevail.

PMID- 23008752
TI  - Release of cyclic phosphatidic acid from gelatin-based hydrogels inhibit colon
      cancer cell growth and migration.
AB  - Microparticle and nanoparticle formulations are widely used to improve the
      bioavailability of low-solubility drugs and as vehicles for organ- and tissue
      specific targeted drug delivery. We investigated the effect of a novel,
      controlled-release form of a bioactive lipid, cyclic phosphatidic acid (cPA), on
      human colon cancer cell line functions. We encapsulated cPA in gelatin-based
      hydrogels and examined its ability to inhibit the viability and migration of HT
      29 and DLD-1 cells in vitro and the LPA-induced activity of the transcription
      factor peroxisome proliferator-activated receptor gamma (PPARgamma). The hydrogel
      delivery system prolonged cPA release into the culture medium. Accordingly, cPA
      hydrogel microspheres substantially inhibited LPA-induced PPARgamma activity and
      cell growth and migration compared with that of cells cultured with cPA alone.
      Thus, hydrogel microspheres are a potential system for stable and efficient
      delivery of bioactive lipids such as cPA and may offer a new strategy for
      targeted colon cancer treatment.

PMID- 23008753
TI  - Primary role of the chromophore bond length alternation in reversible
      photoconversion of red fluorescence proteins.
AB  - Rapid photobleaching of fluorescent proteins can limit their use in imaging
      applications. The underlying kinetics is multi-exponential and strongly depends
      on the local chromophore environment. The first, reversible, step may be
      attributed to a rotation around one of the two exocyclic C-C bonds bridging
      phenol and imidazolinone groups in the chromophore. However it is not clear how
      the protein environment controls this motion - either by steric hindrances or by
      modulating the electronic structure of the chromophore through electrostatic
      interactions. Here we study the first step of the photobleaching kinetics in 13
      red fluorescent proteins (RFPs) with different chromophore environment and show
      that the associated rate strongly correlates with the bond length alternation
      (BLA) of the two bridge bonds. The sign of the BLA appears to determine which
      rotation is activated. Our results present experimental evidence for the
      dominance of electronic effects in the conformational dynamics of the RFP
      chromophore.

PMID- 23008754
TI  - Acquired immunity of transgenic torenia plants overexpressing agmatine
      coumaroyltransferase to pathogens and herbivore pests.
AB  - We investigated the ability of transgenic torenia (Scrophulariaceae) plants to
      resist fungi and arthropod herbivores. Torenia hybrida cv. Summerwave Blue was
      manipulated to produce Arabidopsis agmatine coumaroyltransferase (AtACT). This
      catalyses the last step in the biosynthesis of hydroxycinnamic acid amides
      (HCAAs) which function in defence. Transgenic plants accumulated substantial
      HCAAs, predominantly p-coumaroylagmatine, and the HCAAs were isomerized from the
      trans-form to the cis-form in planta. The transgenic line, accumulated the
      highest amount of endogenous HCAAs (CouAgm at 32.2 uM and total HCAAs at 47.5 uM)
      and this line was resistant to the necrotrophic fungus, Botrytis cinerea. There
      was no resistance, however, in their wild-type progenitors or in other transgenic
      lines accumulating low HCAA amounts. In contrast, the transformants were not
      significantly resistant to three representative herbivores, Frankliniella
      occidentalis, Aphis gossypii, and Tetranychus ludeni.

PMID- 23008755
TI  - The mode of pretransplant dialysis does not affect postrenal transplant outcomes
      in african americans.
AB  - Background. In previous reports with a majority of Caucasian patients, peritoneal
      dialysis (PD) before kidney transplantation has been associated with poor
      outcomes and higher rates of graft thrombosis and infectious complications than
      hemodialysis (HD). We report our experience on the outcomes of prerenal
      transplant peritoneal dialysis in predominantly (73%) African American patient
      population. Methods. A retrospective data analysis of 401 kidney transplants
      performed at our center from 2000 to 2006 was performed. Adult recipients with at
      least three months of pretransplant HD or PD were included. Results. There were
      339 patients on HD and 62 patients on PD. There was no difference in graft (P =
      0.51) and patient survival (P = 0.52) at 1, 3, and 5-years. Patients on HD were
      more likely to experience delayed graft function than PD (38.8% versus 17.7%, P <
      0.005). There was no difference in the incidence of vascular thrombosis or
      posttransplant infectious complications. When only the African American patients
      in the two groups were compared, there were no differences in graft or patient
      survival. Conclusions. Pretransplant peritoneal dialysis is associated with
      excellent patient and renal allograft outcomes in African Americans and does not
      predispose them to an increased risk of infectious or thrombotic complications.

PMID- 23008756
TI  - Optical coherence tomography of retinal and choroidal tumors.
AB  - Optical coherence tomography (OCT) has revolutionized the field of ophthalmology
      since its introduction 20 years ago. Originally intended primarily for retina
      specialists to image the macula, it has found its role in other subspecialties
      that include glaucoma, cornea, and ocular oncology. In ocular oncology, OCT
      provides axial resolution to approximately 7 microns with cross-sectional images
      of the retina, delivering valuable information on the effects of intraocular
      tumors on the retinal architecture. Some effects include retinal edema,
      subretinal fluid, retinal atrophy, photoreceptor loss, outer retinal thinning,
      and retinal pigment epithelial detachment. With more advanced technology, OCT now
      provides imaging deeper into the choroid using a technique called enhanced depth
      imaging. This allows characterization of the thickness and reflective quality of
      small (<3 mm thick) choroidal lesions including choroidal nevus and melanoma.
      Future improvements in image resolution and depth will allow better understanding
      of the mechanisms of visual loss, tumor growth, and tumor management.

PMID- 23008757
TI  - The clinical features and emotional stressors in korean patients with tako-tsubo
      cardiomyopathy.
AB  - Background. Tako-tsubo cardiomyopathy (TTC) is typically triggered by an acute
      emotional or physical stress events. Aim of this study was to investigate the
      impact of emotional stressors on clinical features, laboratory parameters,
      electrocardiographic and echocardiographic findings in patients with TTC.
      Methods. Of 103 patients enrolled from the TTC registry database, fifteen
      patients had emotional triggers (E group), and 88 patients had physical triggers
      or no triggers (other group). Results. Most clinical presentations and in
      hospital courses were similar between the groups. However, E group had higher
      prevalence of chest pain (87 versus 42 %, P = 0.001), palpitation (27 versus 6%,
      P = 0.008), whereas other group had higher prevalence of cardiogenic shock (35
      versus 7%, P = 0.027). E group had significantly higher corrected QT intervals
      (median, 477.5 versus 438 ms, P = 0.001), and left ventricular ejection fraction
      (LVEF) (mean, 45.7 versus 39.6%, P = 0.001), but lower hs-CRP (median, 0.1 versus
      3.3 mg/L, P = 0.001), CK-MB (median, 5.5 versus 11.9 ng/mL, P = 0.047), troponin
      I (median, 1.0 versus 3.2 ng/mL, P = 0.011), and NT-proBNP levels (median, 2145
      versus 4939 pg/mL, P = 0.020). Other group required more frequent hemodynamic
      support and had significantly longer intensive care unit (median, 3 versus 1
      days, P = 0.005) and in-hospital (median, 17 versus 3 days, P = 0.001) durations.
      Conclusion. The clinical features of TTC are different between groups with and
      without preceding emotional stressors. The TTC group with preceding emotional
      stressors was more likely to have preserved cardiovascular reserve and lesser
      likely to require hemodynamic support than other group although the entire
      prognosis of TTC is excellent regardless of triggering stressors.

PMID- 23008758
TI  - Alternative Splicing of a Novel Inducible Exon Diversifies the CASK Guanylate
      Kinase Domain.
AB  - Alternative pre-mRNA splicing has a major impact on cellular functions and
      development with the potential to fine-tune cellular localization,
      posttranslational modification, interaction properties, and expression levels of
      cognate proteins. The plasticity of regulation sets the stage for cells to adjust
      the relative levels of spliced mRNA isoforms in response to stress or
      stimulation. As part of an exon profiling analysis of mouse cortical neurons
      stimulated with high KCl to induce membrane depolarization, we detected a
      previously unrecognized exon (E24a) of the CASK gene, which encodes for a
      conserved peptide insertion in the guanylate kinase interaction domain.
      Comparative sequence analysis shows that E24a appeared selectively in mammalian
      CASK genes as part of a >3,000 base pair intron insertion. We demonstrate that a
      combination of a naturally defective 5' splice site and negative regulation by
      several splicing factors, including SC35 (SRSF2) and ASF/SF2 (SRSF1), drives E24a
      skipping in most cell types. However, this negative regulation is countered with
      an observed increase in E24a inclusion after neuronal stimulation and NMDA
      receptor signaling. Taken together, E24a is typically a skipped exon, which
      awakens during neuronal stimulation with the potential to diversify the protein
      interaction properties of the CASK polypeptide.

PMID- 23008759
TI  - Kinetic Analysis of Guanidine Hydrochloride Inactivation of beta-Galactosidase in
      the Presence of Galactose.
AB  - Inactivation of purified beta-Galactosidase was done with GdnHCl in the absence
      and presence of varying [galactose] at 50 degrees C and at pH 4.5. Lineweaver
      Burk plots of initial velocity data, in the presence and absence of guanidine
      hydrochloride (GdnHCl) and galactose, were used to determine the relevant K(m)
      and V(max) values, with p-nitrophenyl beta-D-galactopyranoside (pNPG) as
      substrate, S. Plots of ln([P](infinity) - [P](t)) against time in the presence of
      GdnHCl yielded the inactivation rate constant, A. Plots of A versus [S] at
      different galactose concentrations were straight lines that became increasingly
      less steep as the [galactose] increased, showing that A was dependent on [S].
      Slopes and intercepts of the 1/[P](infinity) versus 1/[S] yielded k(+0) and
      k'(+0), the microscopic rate constants for the free enzyme and the enzyme
      substrate complex, respectively. Plots of k(+0) and k'(+0) versus [galactose]
      showed that galactose protected the free enzyme as well as the enzyme-substrate
      complex (only at the lowest and highest [galactose]) against GdnHCl inactivation.
      In the absence of galactose, GdnHCl exhibited some degree of non-competitive
      inhibition. In the presence of GdnHCl, galactose exhibited competitive inhibition
      at the lower [galactose] of 5 mM which changed to non-competitive as the
      [galactose] increased. The implications of our findings are further discussed.

PMID- 23008760
TI  - Application of Asymetrical and Hoke Designs for Optimization of Laccase
      Production by the White-Rot Fungus Fomes fomentarius in Solid-State Fermentation.
AB  - Statistical approaches were employed for the optimization of different cultural
      parameters for the production of laccase by the white rot fungus Fomes
      fomentarius MUCL 35117 in wheat bran-based solid medium. first, screening of
      production parameters was performed using an asymmetrical design 2(5)3(3)//16,
      and the variables with statistically significant effects on laccase production
      were identified. Second, inoculum size, CaCl(2) concentration, CuSO(4)
      concentration, and incubation time were selected for further optimization studies
      using a Hoke design. The application of the response surface methodology allows
      us to determine a set of optimal conditions (CaCl(2), 5.5 mg/gs, CuSO(4), 2.5
      mg/gs, inoculum size, 3 fungal discs (6 mm O), and 13 days of static
      cultivation). Experiments carried out under these conditions led to a laccase
      production yield of 150 U/g dry substrate.

PMID- 23008761
TI  - Methicillin-Resistant Staphylococcus aureus Infections in Human Immunodeficiency
      Virus-Infected Children and Adolescents.
AB  - Background. Methicillin-resistant Staphylococcus aureus (MRSA) infection
      incidence has increased in healthy US children. Our objective was to evaluate
      MRSA incidence and correlates in HIV-infected youth. Methods. The CDC-sponsored
      LEGACY study is a US multicenter chart abstraction study of HIV-infected youth.
      We identified MRSA infections among participants with >=1 visit during 2006. We
      used bivariate and multivariable analyses to compare sociodemographic and HIV
      clinical factors between MRSA cases and noncases. Results. Fourteen MRSA
      infections (1 invasive, 12 soft tissue, 1 indeterminate) occurred among 1,813
      subjects (11.1 infections/1,000 patient-years (PY), 95% CI: 11.06-11.14). Most
      (86%) isolates were clindamycin susceptible. Compared with noncases, MRSA cases
      were more likely older (17 versus 14 years), black (100% versus 69%),
      behaviorally HIV infected (43% versus 17%), and in Maryland (43% versus 7%) and
      had viral loads (VL) >1000 copies/mL (86% versus 51%) and lower mean CD4% (18%
      versus 27%) (all P < 0.05). In multivariate analysis, independent risk factors
      were Maryland care site (adjusted odds ratio (aOR) = 9.0), VL >1000 copies/mL
      (aOR = 5.9), and black race (aOR undefined). Conclusions. MRSA occurred at a rate
      of 11.1 infections/1,000 PY in HIV-infected youth but invasive disease was
      uncommon. Geographic location, black race, and increased VL, but not
      immunosuppression, were independently associated with MRSA risk.

PMID- 23008762
TI  - Oral HIV-Associated Kaposi Sarcoma: A Clinical Study from the Ga-Rankuwa Area,
      South Africa.
AB  - Background. Kaposi sarcoma (KS) is one of the most common neoplasms diagnosed in
      HIV-seropositive subjects. Oral involvement is frequent and is associated with a
      poor prognosis. The aim of this study was to characterize the features of oral
      HIV-KS in patients from Ga-Rankuwa, South Africa. Methods. All cases with
      confirmed oral HIV-KS treated at the oral medicine clinic in Ga-Rankuwa from 2004
      to 2010 were included in this retrospective study. Differences between males and
      females with oral HIV-KS in relation to HIV infection status, to oral KS
      presentation and to survival rates were statistically analysed. Results. Twenty
      (54%) of the 37 patients in the study were females and 17 (46%) were males. In 21
      patients (57%), the initial presentation of HIV-KS was in the mouth. Other than
      the fact that females presented with larger (>=10 mm) oral KS lesions (P =
      0.0004), there were no statistically significant gender differences.
      Significantly more patients presented with multiple oral HIV-KS lesions than with
      single lesions (P = 0.0003). Nine patients (24%) developed concomitant facial
      lymphoedema, and these patients had a significantly lower CD4+ T-cell count (28
      cells/mm(3)) compared to the rest of the group (130 cells/mm(3)) (P = 0.01). The
      average CD4+ T-cell count of the patients who died (64 cells/mm(3)) was
      significantly lower (P = 0.0004), there were no statistically significant gender
      differences. Significantly more patients presented with multiple oral HIV-KS
      lesions than with single lesions (P = 0.016) at the time of oral-KS presentation
      than of those who survived (166  cells/mm(3)). CONCLUSIONS: In Ga-Rankuwa, South
      Africa where HIV-KS is prevalent, oral KS affects similarly males and females. A
      low CD4+ T-cell count at the time of oral HIV-KS diagnosis and the development of
      facial lymphoedema during the course of HIV-KS disease portends a poor prognosis.

PMID- 23008763
TI  - Personality and Major Depression among Directly Exposed Survivors of the Oklahoma
      City Bombing.
AB  - Background. Few disaster studies have specifically examined personality and
      resilience in association with disaster exposure, posttraumatic stress disorder
      (PTSD), and major depression. Methods. 151 directly-exposed survivors of the
      Oklahoma City bombing randomly selected from a bombing survivor registry
      completed PTSD, major depression, and personality assessments using the
      Diagnostic Interview Schedule for DSM-IV and the Temperament and Character
      Inventory, respectively. Results. The most prevalent postdisaster psychiatric
      disorder was bombing-related PTSD (32%); major depression was second in
      prevalence (21%). Bombing-related PTSD was associated with the combination of low
      self-directedness and low cooperativeness and also with high self-transcendence
      and high harm avoidance in most configurations. Postdisaster major depression was
      significantly more prevalent among those with (56%) than without (5%) bombing
      related PTSD (P < .001) and those with (72%) than without (14%) predisaster major
      depression (P < .001). Incident major depression was not associated with the
      combination of low self-directedness and low cooperativeness. Conclusions.
      Personality features can distinguish resilience to a specific life-threatening
      stressor from general indicators of well-being. Unlike bombing-related PTSD,
      major depression was not a robust marker of low resilience. Development and
      validation of measures of resilience should utilize well-defined diagnoses
      whenever possible, rather than relying on nonspecific measures of psychological
      distress.

PMID- 23008764
TI  - Sustained adoption of an evidence-based treatment: a survey of clinicians
      certified in problem-solving therapy.
AB  - Training models that incorporate case supervision in addition to didactic
      instruction appear to be effective in maximizing clinicians' proficiency in
      evidence-based treatments (EBTs). However, it is unknown the extent to which
      these models promote sustained adoption of EBTs. We describe the results of an
      online survey on post-training utilization of an EBT, problem-solving therapy
      (PST), among 40 clinicians highly trained in PST. Seventy-five percent of the
      survey's 40 respondents reported that they continued to use PST in their clinical
      practices. Many PST-trained clinicians reported that they had modified the PST
      protocol in their clinical practices according to patient characteristics or
      preferences. Considering these results, we recommend emphasizing patient
      variability and treatment tailoring throughout the training process as a means
      for promoting clinicians' sustained adoption of EBTs.

PMID- 23008765
TI  - Reoperation following Pancreaticoduodenectomy.
AB  - Introduction. The literature on reoperation following pancreaticoduodenectomy is
      sparse and does not address all concerns. Aim. To analyze the incidence, causes,
      and outcome of patients undergoing reoperations following
      pancreaticoduodenectomy. Methods. Retrospective analysis of 520 consecutive
      patients undergoing pancreaticoduodenectomy from May 1989 to September 2010.
      Results. 96 patients (18.5%) were reoperated; 72 were early, 18 were late, and 6
      underwent both early and late reoperations. Indications for early reoperation
      were post pancreatectomy hemorrhage in 53 (68%), pancreatico-enteric anastomotic
      leak in 10 (13%), hepaticojejunostomy leak in 3 (3.8%), duodenojejunostomy leak
      in 4 (5%), intestinal obstruction in 1 (1.2%) and miscellaneous causes in 7 (9%).
      Patients reoperated early did not fare poorly on long-term follow up. Indications
      for late reoperations were complications of index surgery (n = 12), recurrence of
      the primary disease (n = 8), complications of adjuvant radiotherapy (n = 3), and
      gastrointestinal bleed (n = 1). The median survival of 16 patients reoperated
      late without recurrent disease was 49 months. Conclusion. Early reoperations
      following pancreaticoduodenectomy, commonly for post pancreatectomy hemorrhage,
      carries a high mortality due to associated sepsis, but has no impact on long-term
      survival. Long-term complications related to pancreaticoduodenectomy and adjuvant
      radiotherapy can be managed successfully with good results.

PMID- 23008766
TI  - Rectal cancer: multimodal treatment approach.

PMID- 23008767
TI  - Nurse managers' leadership styles in Finland.
AB  - Nurse managers who can observe their own behaviour and its effects on employees
      can adjust to a better leadership style. The intention of this study was to
      explore nurses' and supervisors' perceptions of nurse managers' leadership
      styles. Open-ended interviews were conducted with 11 nurses and 10 superiors. The
      data were analysed by content analysis. In the study, six leadership styles were
      identified: visionary, coaching, affiliate, democratic, commanding, and
      isolating. Job satisfaction and commitment as well as operation and development
      work, cooperation, and organizational climate in the work unit were the factors,
      affected by leadership styles. The nurse managers should consider their
      leadership style from the point of view of employees, situation factors, and
      goals of the organization. Leadership styles where employees are seen in a
      participatory role have become more common.

PMID- 23008768
TI  - The Role of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in
      Assessing the Response to Neoadjuvant Treatment in Patients with Osteosarcoma.
AB  - Aim. The objective of this study is to systematically review the role of positron
      emission tomography (PET) and PET/computed tomography (PET/CT) with fluorine-18
      fluorodeoxyglucose (FDG) in assessing the response to neoadjuvant treatment in
      patients with osteosarcoma (OS). Methods. A comprehensive literature search of
      published studies through March 2012 in PubMed/MEDLINE, Embase, and Scopus
      databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was
      performed. Results. Twenty-two studies have investigated the role of FDG-PET and
      FDG-PET/CT in the evaluation of response to neoadjuvant treatment with either
      chemotherapy or radiation therapy in patients with OS. The main findings of these
      studies are presented. Conclusion. FDG-PET or PET/CT seems to be sensitive and
      reliable diagnostic tools in the assessment of metabolic response to treatment in
      patients with OS, after baseline PET evaluation has been performed in advance.
      However, false positive findings due to inflammation in sites of tumoral response
      should be considered.

PMID- 23008769
TI  - Methods for Assessing Expiratory Flow Limitation during Tidal Breathing in COPD
      Patients.
AB  - Patients with severe COPD often exhale along the same flow-volume curve during
      quite breathing as during forced expiratory vital capacity manoeuvre, and this
      has been taken as indicating expiratory flow limitation at rest (EFL(T)).
      Therefore, EFL(T), namely, attainment of maximal expiratory flow during tidal
      expiration, occurs when an increase in transpulmonary pressure causes no increase
      in expiratory flow. EFL(T) leads to small airway injury and promotes dynamic
      pulmonary hyperinflation with concurrent dyspnoea and exercise limitation. In
      fact, EFL(T) occurs commonly in COPD patients (mainly in GOLD III and IV stage)
      in whom the latter symptoms are common. The existing up-to-date physiological
      methods for assessing expiratory flow limitation (EFL(T)) are reviewed in the
      present work. Among the currently available techniques, the negative expiratory
      pressure (NEP) has been validated in a wide variety of settings and disorders.
      Consequently, it should be regarded as a simple, non invasive, most practical,
      and accurate new technique.

PMID- 23008770
TI  - Tolerance of an aquatic power training program by older adults with symptomatic
      knee osteoarthritis.
AB  - Objective. To determine the tolerance and feasibility of aquatic-based power
      training for improving lower limb muscle power, impairments, and mobility in
      adults with symptomatic knee OA. Participants. Twenty-nine adults, age 50 years
      and over, with symptomatic knee OA (ACR clinical criteria) and mobility
      limitation (400-meter walk time slower than median for sex and decade) completed
      45-minute aquatic power training sessions twice weekly for 6 weeks. Main Outcome
      Measurements. Prospective outcomes included tolerance of the program, as well as
      change in stair climb power, 400-meter walk time, overall and knee-specific pain,
      activities of daily living (ADL), quality of life (QOL), and lower limb function
      at 6- and 12-week follow-up. Results. The training intensity required
      modification for 9 of the 29 participants. Lower limb muscle power, ADL, QOL, and
      overall pain were improved immediately and 6 weeks following completion (all P <
      0.05). However, 400-meter walk times, and lower limb function did not differ from
      baseline. Conclusions. A 6-week aquatic rehabilitation program appears to be well
      tolerated by adults with symptomatic knee OA with mobility limitations and may
      result in improved lower limb muscle power, symptoms, ADL, and QOL. However, this
      intervention may have insufficient specificity or intensity for improving
      physical function.

PMID- 23008771
TI  - An economical high-throughput protocol for multidimensional fractionation of
      proteins.
AB  - A sequential protocol of multidimensional fractionation was optimised to enable
      the comparative profiling of fractions of proteomes from cultured human cells.
      Differential detergent fractionation was employed as a first step to obtain
      fractions enriched for cytosolic, membrane/organelle, nuclear, and cytoskeletal
      proteins. Following buffer exchange using gel-permeation chromatography,
      cytosolic proteins were further fractionated by 2-dimensional chromatography
      employing anion-exchange followed by reversed-phase steps. Chromatographic
      fractions were shown to be readily compatible with 1- and 2-dimensional gel
      electrophoresis or with direct analysis by mass spectrometry using linear-MALDI
      TOF-MS. Precision of extraction was confirmed by reproducible SDS-PAGE profiles,
      MALDI-TOF-MS spectra, and quantitation of trypsinolytic peptides using LC-MS/MS
      (MRM) analyses. Solid phases were immobilised in disposable cartridges and mobile
      phase flow was achieved using a combination of centrifugation and vacuum pumping.
      These approaches yielded parallel sample handling which was limited only by the
      capacities of the employed devices and which enabled both high-throughput and
      experimentally precise procedures, as demonstrated by the processing of
      experimental replicates. Protocols were employed at 10 mg scale of extracted cell
      protein, but these approaches would be directly applicable to both smaller and
      larger quantities merely by adjusting the employed solid- and mobile-phase
      volumes. Additional potential applications of the fractionation protocol are
      briefly described.

PMID- 23008772
TI  - Efficacy of a multimodal cognitive rehabilitation including psychomotor and
      endurance training in Parkinson's disease.
AB  - Mild cognitive impairment, especially executive dysfunction might occur early in
      the course of Parkinson's disease. Cognitive training is thought to improve
      cognitive performance. However, transfer of improvements achieved in paper and
      pencil tests into daily life has been difficult. The aim of the current study was
      to investigate whether a multimodal cognitive rehabilitation programme including
      physical exercises might be more successful than cognitive training programmes
      without motor training. 240 PD-patients were included in the study and randomly
      allocated to three treatment arms, group A cognitive training, group B cognitive
      training and transfer training and group C cognitive training, transfer training
      and psychomotor and endurance training. The primary outcome measure was the ADAS
      Cog. The secondary outcome measure was the SCOPA-Cog. Training was conducted for
      4 weeks on a rehabilitation unit, followed by 6 months training at home.
      Caregivers received an education programme. The combination of cognitive training
      using paper and pencil and the computer, transfer training and physical training
      seems to have the greatest effect on cognitive function. Thus, patients of group
      C showed the greatest improvement on the ADAS-Cog and SCOPA-COG and were more
      likely to continue with the training programme after the study.

PMID- 23008773
TI  - Divalent Metal Ion Transport across Large Biological Ion Channels and Their
      Effect on Conductance and Selectivity.
AB  - Electrophysiological characterization of large protein channels, usually
      displaying multi-ionic transport and weak ion selectivity, is commonly performed
      at physiological conditions (moderate gradients of KCl solutions at decimolar
      concentrations buffered at neutral pH). We extend here the characterization of
      the OmpF porin, a wide channel of the outer membrane of E. coli, by studying the
      effect of salts of divalent cations on the transport properties of the channel.
      The regulation of divalent cations concentration is essential in cell metabolism
      and understanding their effects is of key importance, not only in the channels
      specifically designed to control their passage but also in other multiionic
      channels. In particular, in porin channels like OmpF, divalent cations modulate
      the efficiency of molecules having antimicrobial activity. Taking advantage of
      the fact that the OmpF channel atomic structure has been resolved both in water
      and in MgCl(2) aqueous solutions, we analyze the single channel conductance and
      the channel selectivity inversion aiming to separate the role of the electrolyte
      itself, and the counterion accumulation induced by the protein channel charges
      and other factors (binding, steric effects, etc.) that being of minor importance
      in salts of monovalent cations become crucial in the case of divalent cations.

PMID- 23008774
TI  - Cardiomyopathy-Related Mutations in Cardiac Troponin C, L29Q and G159D, Have
      Divergent Effects on Rat Cardiac Myofiber Contractile Dynamics.
AB  - Previous studies of cardiomyopathy-related mutations in cardiac troponin C (cTnC)
      L29Q and G159D-have shown diverse findings. The link between such mutant effects
      and their divergent impact on cardiac phenotypes has remained elusive due to lack
      of studies on contractile dynamics. We hypothesized that a cTnC mutant-induced
      change in the thin filament will affect global myofilament mechanodynamics
      because of the interactions of thin filament kinetics with both Ca(2+) binding
      and crossbridge (XB) cycling kinetics. We measured pCa-tension relationship and
      contractile dynamics in detergent-skinned rat cardiac papillary muscle fibers
      reconstituted with the recombinant wild-type rat cTnC (cTnC(WT)), cTnC(L29Q), and
      cTnC(G159D) mutants. cTnC(L29Q) fibers demonstrated a significant decrease in
      Ca(2+) sensitivity, but cTnC(G159D) fibers did not. Both mutants had no effect on
      Ca(2+)-activated maximal tension. The rate of XB recruitment dynamics increased
      in cTnC(L29Q) (26%) and cTnC(G159D) (25%) fibers. The rate of XB distortion
      dynamics increased in cTnC(G159D) fibers (15%). Thus, the cTnC(L29Q) mutant
      modulates the equilibrium between the non-cycling and cycling pool of XB by
      affecting the on/off kinetics of the regulatory units (Tropomyosin-Troponin);
      whereas, the cTnC(G159D) mutant increases XB cycling rate. Different effects on
      contractile dynamics may offer clue regarding how cTnC(L29Q) and cTnC(G159D)
      cause divergent effects on cardiac phenotypes.

PMID- 23008775
TI  - Influence of bisphosphonate treatment on medullary macrophages and osteoclasts:
      an experimental study.
AB  - Nitrogen-containing bisphosphonates are widely used for treating diverse bone
      pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone
      resorption. It remains unknown whether the mechanism of action is by decreasing
      osteoclast number, impairing osteoclast function, or whether they continue to
      effectively inhibit bone resorption despite the increase in osteoclast number.
      There is increasing evidence that bisphosphonates also act on bone marrow cells
      like macrophages and monocytes. The present work sought to evaluate the dynamics
      of preosteoclast fusion and possible changes in medullary macrophage number in
      bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate,
      alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU) on day
      7, 28, or 34 of the experiment. Histomorphometric studies were performed to study
      femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc); number of BrdU
      positive nuclei (N.Nu BrdU+/Oc); percentage of BrdU-positive nuclei per
      osteoclast (%Nu.BrdU+/Oc); medullary macrophage number (mac/mm(2)) and
      correlation between N.Nu/Oc and mac/mm(2). Results showed bisphosphonate-treated
      animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast
      fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased
      mac/mm(2). Considering the common origin of osteoclasts and macrophages, the
      increased demand for precursors of the osteoclast lineage may occur at the
      expense of macrophage lineage precursors.

PMID- 23008776
TI  - Efficacy of fibrin glue on seroma formation after breast surgery.
AB  - Background and Objectives. This study was designed to determine the effectiveness
      of fibrin glue plus conventional drain placement versus conventional drain
      placement in the prevention of seromas after breast procedures. Among methods
      employed to reduce seroma magnitude and duration, fibrin glue has been proposed
      in numerous studies, with controversial results. Design and Setting. A
      prospective, randomized, controlled study of subjects who were randomized into
      control and experimental groups was conducted. Methods. Collected data included
      age, surgeon, medical and surgical history, comorbidities, procedure performed,
      number of axillary nodes, number of positive axillary nodes collected, final
      pathologic diagnosis, cancer stage, hospital stay, postoperative day of drain
      removal, complications, incidence of seroma formation, interval to seroma
      resolution, and number of postoperative visits. Results. Analysis of 60 patients
      showed similarly matched groups. Seroma formation rate was 24.1% in the control
      group and 16.1% in the fibrin glue group. The rate of wound complications was
      similar. Conclusions. Although use of fibrin sealant resulted in a nonsignificant
      decrease in seroma formation rate compared with that of drain placement, the
      higher cost and cumbersome technique tend to indicate that there is no advantage
      to using fibrin glue over drain placement with the technique described.

PMID- 23008777
TI  - Radiopacity evaluation of contemporary luting cements by digitization of images.
AB  - Objective. The aim of this study was to evaluate the radiopacity of two
      conventional cements (Zinc Cement and Ketac Cem Easymix), one resin-modified
      glass ionomer cement (RelyX Luting 2) and six resin cements (Multilink, Bistite
      II DC, RelyX ARC, Fill Magic Dual Cement, Enforce and Panavia F) by digitization
      of images. Methods. Five disc-shaped specimens (10 * 1.0 mm) were made for each
      material, according to ISO 4049. After setting of the cements, radiographs were
      made using occlusal films and a graduated aluminum stepwedge varying from 1.0 to
      16 mm in thickness. The radiographs were digitized, and the radiopacity of the
      cements was compared with the aluminum stepwedge using the software VIXWIN-2000.
      Data (mmAl) were submitted to one-way ANOVA and Tukey's test (alpha = 0.05).
      Results. The Zinc Cement was the most radiopaque material tested (P < 0.05). The
      resin cements presented higher radiopacity (P < 0.05) than the conventional
      (Ketac Cem Easymix) or resin-modified glass ionomer (RelyX Luting 2) cements,
      except for the Fill Magic Dual Cement and Enforce. The Multilink presented the
      highest radiopacity (P < 0.05) among the resin cements. Conclusion. The glass
      ionomer-based cements (Ketac Cem Easymix and RelyX Luting 2) and the resin
      cements (Fill Magic Dual Cement and Enforce) showed lower radiopacity values than
      the minimum recommended by the ISO standard.

PMID- 23008778
TI  - Effect of Echium amoenum Fisch. et Mey a Traditional Iranian Herbal Remedy in an
      Experimental Model of Acute Pancreatitis.
AB  - Acute pancreatitis is a morbid inflammatory condition of pancreas with limited
      specific therapy. Enhanced oxidative stress plays an important role in induction
      and progression of acute pancreatitis. So reducing oxidative stress may relieve
      this pathogenic process. Echium amoenum Fisch. and Mey has been implemented in
      Iranian folk medicine for several centuries. Antioxidant, analgesic,
      immunomodulatory, and anxiolytic properties of E. amoenum suggest that this plant
      may have beneficial effects in the management of acute pancreatitis. The aim of
      this study was to evaluate the protective effect of petals of E. amoenum extract
      (EAE) on a murine model of pancreatitis. Acute pancreatitis was induced by five
      intraperitoneal (i.p.) injection of cerulein (50 MUg/kg) with 1h intervals which
      was characterized by pancreatic inflammation and increase in the serum level of
      digestive enzymes, in comparison to normal mice. EAE (100, 200, and 400 mg/kg)
      was administered i.p., 30 minutes before induction of pancreatitis. Pretreatment
      with EAE (400 mg/kg) reduced significantly the inflammatory response of cerulein
      induced acute pancreatitis by ameliorating pancreatic edema, amylase and lipase
      serum levels, proinflammatory cytokines, myeloperoxidase activity, lipid
      peroxidation and pathological alteration. These results show that EAE attenuates
      the severity of cerulein-induced acute pancreatitis with an anti-inflammatory,
      immunomodulatory and antioxidant effects.

PMID- 23008779
TI  - Need for nucleic Acid testing in countries with high prevalence of transfusion
      transmitted infections.
AB  - Introduction. In India, family/replacement donors still provide more than 45% of
      the collected blood. With increasing voluntary blood donation and the still
      prevalent infectious diseases in donors, we need to augment transfusion
      transmitted infections (TTIs) testing before use. Our study was aimed to know the
      seroprevalence of TTIs among the donors of Rajasthan and the need for newer
      technologies like nucleic acid testing (NAT). Materials and Methods. Enhanced
      chemiluminescence immunoassay (ECi) was used for detection of HBsAg, anti-HIV,
      and anti-HCV in donor serum. 50% of the blood units which were negative on ECi
      were randomly selected and subjected to NAT testing for HBV, HCV, and HIV.
      Results. The total seroprevalence of TTIs is 2.62%. Of the randomly selected
      donor units negative by ECi, 8 turned out to be reactive on NAT testing: 4 were
      voluntary and 4 were family/replacement donors. Combined NAT yield (NAT
      reactive/seronegative) for HIV, HCV, and HBV was 0.034% (1 in 2972 donations).
      All the 8 reactive samples were positive for HBV DNA. Conclusion. In countries
      with a high prevalence of TTIs like India there are likely to be a significant
      number of window period donations that can be identified by NAT which may be
      implemented in blood centers allover India with serological testing to provide
      safe blood and cost alone should not be a deterrent to the government and
      implementing agencies.

PMID- 23008780
TI  - The multifaceted granulosa cell tumours-myths and realities: a review.
AB  - Background. Granulosa cell tumors (GCTs), representing ~2% of ovarian tumours,
      are poorly understood neoplasms with unpredictable and undetermined biological
      behaviour. Design. 5 unusual presentations of GCT and a retrospective 14-year
      (1997-2011) surgical pathology review based on patient sex, age, tumour type and
      concurrent pathology findings are presented to discuss the "myths and realities"
      of GCTs in the context of relevant evidence-based literature. Results. The 5
      index cases included (1) a 5 month-old boy with a left testicular mass, (2) a 7
      day-old neonate with a large complex cystic mass in the abdomen, (3) a 76-year
      old woman with an umbilical mass, (4) a 64-year-old woman with a complex solid
      cystic pelvic mass, and (5) a 45 year-old woman with an acute abdomen.
      Pathological analysis confirmed the final diagnosis as (1) juvenile GCT, (2)
      macrofollicular GCT, (3) recurrent GCT 32 years later, (4) collision tumour:
      colonic adenocarcinoma and GCT, and (5) ruptured GCT. Conclusion. GCT is best
      considered as an unusual indolent neoplasm of low malignant potential with late
      recurrences that can arise in the ovaries and testicles in both the young and the
      old. Multifaceted clinical presentations coupled with the unpredictable
      biological behaviour with late relapses are diagnostic pitfalls necessitating a
      high degree of suspicion for accurate clinical and pathological diagnosis.

PMID- 23008781
TI  - Susceptibility of Dermatophytes to Thiabendazole Using CLSI Broth Macrodilution.
AB  - Objective. To evaluate in vitro antifungal activity of thiabendazole against
      strains of dermatophytes using a reference method for filamentous fungi.
      Materials and Methods. Dermatophytes' susceptibility to thiabendazole (TBZ) and
      fluconazole (FCZ) was evaluated using macrodilution method of protocol M38-A2 of
      the Clinical and Laboratory Standards Institute (CLSI). Results. MIC ranges of
      TBZ for all strains were narrower and/or smaller than those of FCZ. TBZ showed a
      significantly greater potency than FCZ (P = 0.05) against all isolates.
      Discussion. Although there have been approaches to evaluate the antifungal
      activity of TBZ in human mycoses, no tests had been made with a standardized
      protocol. Susceptibility data resulted from this study shows that although TBZ is
      not a particularly strong inhibitor of dermatophytes, it displays a stable and
      constant effect against all isolates tested. Conclusion. Results show that TBZ is
      more effective against strains of dermatophytes than FCZ. We acknowledge the
      antifungal effect of TBZ against dermatophyte isolates.

PMID- 23008782
TI  - Counselling for patients and family members: a follow-up study in the emergency
      department.
AB  - Although the research indicates that patients and family members are not fully
      satisfied with the counselling they receive, little is known about the quality of
      counselling in more detail. The purpose of the study was to describe patients'
      and their family members' experiences about counselling in emergency department,
      and follow how these experiences possibly change after the educational
      intervention for the whole nursing staff of the ED ward. The pre-test-post-test
      follow-up design was implemented including online continuing education for ED
      staff. The data were collected via questionnaires from patients and their family
      members in two phases and analyzed statistically. After online education of
      staff, experiences of patients and family members concerning counselling were
      better than before the education. Especially, family members' satisfaction had
      increased. However, our results also indicated that patients and family members
      desire more information for example, regarding medications. Care practices had
      developed towards family-centeredness, which patients and family members
      appreciate. Online education proved also in some degree its usefulness in
      educating ED staff, by offering the same education to a staff which works in
      shifts. Furthermore, family presence and participation practices should be
      developed by offering possibilities for families to stay with each other on ED
      ward.

PMID- 23008783
TI  - MMP-2 and sTNF-R1 Variability in Patients with Essential Hypertension: 1-Year
      Follow-Up Study.
AB  - The aim of this study is to analyze MMP-2 and sTNF-R1 variability, potent
      predictors of cardiovascular events, in stable hypertensive patients during a 12
      month followup. 234 asymptomatic patients (age 60 +/- 13, 136 male) out of 252
      patients with essential hypertension were followed up. MMP-2 and sTNF-R1 were
      measured at baseline and after 12 months (stage I). To compare MMP-2 and sTNF-R1
      levels over time interval, we used the statistical method of Bland-Altman. MMP-2
      and sTNF-R1 reproducibility was good in our patients for the two intervals with a
      coefficient of reproducibility of 8.2% and 11.3%, respectively. The percentages
      of patients within 1.96 * standard deviation of the mean were 93.6% and 92.7%. An
      elevated coefficient of correlation was obtained for MMP-2, basal versus stage I
      (r = 0.55, P < 0.0001) and for sTNF-R1 (r = 0.75, P < 0.0001). There is good
      stability in MMP-2 and sTNF-R1 levels in a followup study of patients with stable
      hypertension. As a consequence, assessment of its concentrations may be a useful
      tool for monitoring the follow-up of these patients. Measured variations in MMP-2
      and sTNF-R1 levels, exceeding 8.2% and 11.3%, respectively, may indicate an
      increase in cardiovascular risk, thus, could be used to optimizing treatment than
      blood pressure control alone.

PMID- 23008785
TI  - Dens evaginatus in proximal surface of mandibular premolar: a rare presentation.
AB  - Dens evaginatus is a developmental anomaly that is characterized by occurrence of
      an extra cusp-like structure projecting from the crown portion of the tooth.
      Unusual extension of enamel has been found in posterior teeth as enamel pearl or
      as cervical enamel extensions from the cementoenamel junction or at the furcation
      areas. We hitherto report a case of extra enamel formation from the proximal
      surface of the crown in a mandibular premolar, a finding that has previously not
      been reported.

PMID- 23008784
TI  - Plasmablastic lymphoma of gingiva mimicking a reactive lesion: a case report.
AB  - Oral plasmablastic lymphoma (PBL) is a rare malignancy, associated with HIV or
      other immunocompromised conditions. The lesion constituted a new subtype of
      diffuse large B-cell lymphoma and proposed a distinct entity based on its basic
      morphology, its clinical behaviour involving predominantly extramedullary sites
      (particularly oral cavity), and its limited antigenic phenotype data suggesting
      plasmacytic differentiation. Authors here report a case of apparently healthy
      individual aged 35 years, presenting one-month history of swelling associated
      with loosened teeth around upper anteriors. Following incisional biopsy, routine
      histopathologic and immunohistochemical studies, the diagnosis of plasmablastic
      lymphoma was given.

PMID- 23008786
TI  - The onset of enhanced intestinal permeability and food sensitivity triggered by
      medication used in dental procedures: a case report.
AB  - Enhanced intestinal permeability and food sensitivity are two of the many proven
      causes of gastrointestinal disorders. This present report describes a woman with
      no previous gastrointestinal (GI) complaints, who underwent dental root canal,
      bone graft, and implant procedures. Postsurgery she experienced an allergic
      reaction to the combined medications. In the weeks that followed, she presented
      with multiple food intolerances. Four weeks after the final dental procedure, she
      was assessed serologically for mucosal immune function, salivary, and blood
      gluten reactivity, intestinal permeability, and other food sensitivities.
      Compared to her test reports from two months prior to her first dental procedure,
      the patient's results showed high total secretory IgA (SIgA) and elevated
      salivary antibodies to alpha-gliadin, indicating abnormal mucosal immunity and
      loss of tolerance to gluten. Her serologic assessments revealed immunoglobulin G
      (IgG) and IgA antibodies to a range of wheat/gluten proteins and peptides, gut
      bacterial endotoxins and tight junction proteins. These test results indicate gut
      dysbiosis, enhanced intestinal permeability, systemic gluten-reactivity, and
      immune response to other dietary macromolecules. The present case suggests that
      patients who experience severe allergic or pseudoallergic reactions to medication
      should be assessed and monitored for gut dysfunction. If left untreated this
      could lead to autoimmune reactions to self tissues.

PMID- 23008787
TI  - Successful Control of Disseminated Intravascular Coagulation by Recombinant
      Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute
      Promyelocytic Leukemia.
AB  - Disseminated intravascular coagulation (DIC) frequently occurs in patients with
      acute promyelocytic leukemia (APL). With the induction of therapy in APL using
      all-trans retinoic acid (ATRA), DIC can be controlled in most cases as ATRA
      usually shows immediate improvement of the APL. However, arsenic trioxide (ATO)
      which has been used for the treatment of relapse in APL patients has shown to
      take time to suppress APL cells, therefore the control of DIC in APL with ATO
      treatment is a major problem. Recently, the recombinant soluble thrombomodulin
      fragment has received a lot of attention as the novel drug for the treatment of
      DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC
      was successfully and safely controlled by rTM during treatment with ATO.

PMID- 23008788
TI  - Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human
      Pathogen Uncommon in Caucasian Women.
AB  - Background. Corynebacterium kroppenstedtii (Ck) was first described in 1998 from
      human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is
      rarely isolated from breast abscesses and granulomatous mastitis in Caucasian
      women. Case Presentation. We herein report a case of recurrent breast abscesses
      in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast
      abscesses, even in Caucasian women, the possible involvement of Ck should be
      investigated. The current lack of such investigations, probably due to the
      difficulty to detect Ck, may cause the underestimation of such an aetiology.

PMID- 23008789
TI  - A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult.
AB  - Respiratory syncytial virus (RSV) is commonly known to cause an influenza-like
      illness. However, it can also cause more severe disease in young children and
      older adults comprising of organ transplant patients with immunocompromised
      status. Till date, only four cases of RSV infections have been reported in HIV
      positive adults. We describe here a case of HIV-positive female with relatively
      preserved immune function who presented with RSV infection requiring ventilation
      and showed improvement after prompt treatment with intravenous immunoglobulin.

PMID- 23008790
TI  - MRI findings of causalgia of the lower extremity following transsphenoidal
      resection of pituitary tumor.
AB  - Background. Causalgia is continuing pain, allodynia, or hyperalgesia after nerve
      injury with edema, changes in skin blood flow, or abnormal sudomotor activity.
      Here we report a case of lower extremity causalgia following elective
      transsphenoidal resection of a pituitary tumor in a young man. Clinical
      Presentation. A 33-year-old man with acromegaly underwent elective sublabial
      transsphenoidal resection of his pituitary tumor. During the three-hour surgery,
      the lower limbs were kept in a supine, neutral position with a pillow under the
      knees. The right thigh was slightly internally rotated with a tape to expose
      fascia lata, which was harvested to repair the sella. Postoperatively, he
      developed causalgia in a distal sciatic and common peroneal nerve distribution.
      Pain was refractory to several interventions. Finally, phenoxybenzamine improved
      his pain significantly. Conclusions. Malpositioning in the operating room
      resulted in causalgia in this young man. Phenoxybenzamine improved, and
      ultimately resolved, his symptoms. Improvement in his pain symptoms correlated
      with resolution of imaging changes in the distal sciatic and peroneal nerves on
      the side of injury.

PMID- 23008791
TI  - Amelanotic cellular blue nevus: an unusual iris localization.
AB  - The authors describe the first case of eye amelanotic cellular blue nevus
      reported in literature and discuss the main differential diagnosis.

PMID- 23008792
TI  - Bilateral asynchronous renal cell carcinoma with metastatic involvement of the
      tongue.
AB  - Renal cell carcinoma (RCC) has a propensity for distant organ metastasis and late
      recurrence, involving not only the ipsilateral but also contralateral kidney.
      Lingual metastasis by RCC is rare. We present an unusual case of bilateral
      asynchronous RCC. Involvement of the right kidney was discovered only after a
      metastatic tongue lesion was diagnosed. The original RCC had been treated by left
      nephrectomy 14 years previously. Due to end-stage primary pulmonary malignancy,
      and poor function of the remaining kidney, immunotherapy was unsuitable.
      Palliative local resection of the lingual metastasis alleviated functional
      difficulties and was preventative against airway obstruction, but the patient
      died five months later.

PMID- 23008793
TI  - Metastatic parotid myoepithelial carcinoma in a 7-year-old boy.
AB  - Myoepithelial carcinoma is a rare malignancy of the parotid gland that is usually
      seen in adults. We report the first case in children of myoepithelial carcinoma
      of the parotid gland with massive invasion of the facial nerve and metastasis to
      cervical lymph nodes. Due to its rarity, the treatment and the clinical course of
      this tumor are not well defined yet. We performed a total parotidectomy, a
      modified neck dissection, and a postoperative radiotherapy in 7-year-old boy.
      Sparing of the facial nerve was impossible; it was sacrificed and grafted with a
      sural nerve. Histopathology confirmed the diagnosis of a parotid gland carcinoma
      and immunohistochemical markers showed that the tumor cells express cytokeratin,
      epithelial membrane antigen, cytokeratin 7, smooth muscle actin, P63, CEA, and
      S100. This pattern of immunostaining is consistent with the diagnosis of
      myoepithelial carcinoma. On the postoperative tenth month he presented with a
      pulmonary and lumbar vertebra metastasis.

PMID- 23008794
TI  - Pediatric-isolated auricular erythromelalgia: a case report.
AB  - Erythromelalgia is a rare disorder that typically affects the skin of the feet,
      hands, or both, that is characterized by red skin, warmth, and a burning quality
      of pain. It usually affects both sides of the body, but may manifest
      unilaterally. Cooling of the affected areas usually results in symptom relief. We
      report a case of a young boy with erythromelalgia of the ears.

PMID- 23008795
TI  - Intramuscular dirofilariasis mimicking an orbital metastasis in a patient with
      breast cancer.
AB  - We present the unusual case of a 74 year-old female with a history of breast
      cancer who presented with acute painless orbital swelling and vertical diplopia.
      MRI revealed a focal enhancing mass within the superior rectus muscle. As the
      concern for metastatic disease was high, surgical biopsy was performed and
      revealed an unusual mimicker of metastatic disease, the parasitic infection
      dirofilariasis.

PMID- 23008796
TI  - Idiopathic lymphocele: a possible diagnosis for infraclavicular masses.
AB  - Lymphoceles are usually related to trauma or surgery, and its spontaneous
      development is rare. The aim of this paper is to report an uncommon case of
      idiopathic lymphocele located on the right infraclavicular region, in a female
      patient with no previous local trauma or surgery and unremarkable medical
      history. The diagnose was suggested by the tomographic aspect of the lesion and
      confirmed by ultrasound-guided fluid aspiration and cytological analysis. The
      authors also provide a brief review of the most important thing diagnostic
      features and treatment options for this condition. For the practicing clinician,
      the most important is to achieve an accurate diagnose and to choose the proper
      therapeutic method according to each clinical scenario.

PMID- 23008797
TI  - The Relation between Inflammation and Neuropsychological Test Performance.
AB  - Background. Considerable research documents an association between pro- and anti
      inflammatory markers and Alzheimer's disease (AD), yet the differential relation
      between these markers and neuropsychological functioning in AD and nondemented
      controls has received less attention. The current study sought to evaluate the
      relationship between peripheral markers of inflammation (both pro- and anti
      inflammatory) and neuropsychological functioning through the Texas Alzheimer's
      Research and Care Consortium (TARCC) cohort. Methods. There were 320 participants
      (Probable AD n = 124, Controls n = 196) in the TARCC Longitudinal Research Cohort
      available for analysis. Regression analyses were utilized to examine the relation
      between proinflammatory and anti-inflammatory markers and neuropsychological
      functioning. Follow-up analyses were conducted separately by case versus control
      status. Results. Proinflammatory and anti-inflammatory markers were found to be
      associated with neuropsychological testing. Third tertile proinflammatory markers
      were negatively associated with measures of attention and language, and anti
      inflammatory markers were positively associated with measures of immediate verbal
      memory and delayed verbal and visual memory. Conclusions. These findings support
      the link between peripheral inflammatory markers and neuropsychological
      functioning and suggest the utility of examining profiles of inflammatory markers
      in the future.

PMID- 23008798
TI  - New insights into ligand-receptor pairing and coevolution of relaxin family
      peptides and their receptors in teleosts.
AB  - Relaxin-like peptides (RLN/INSL) play diverse roles in reproductive and
      neuroendocrine processes in placental mammals and are functionally associated
      with two distinct types of receptors (RXFP) for each respective function. The
      diversification of RLN/INSL and RXFP gene families in vertebrates was
      predominantly driven by whole genome duplications (2R and 3R). Teleosts
      preferentially retained duplicates of genes putatively involved in neuroendocrine
      regulation, harboring a total of 10-11 receptors and 6 ligand genes, while most
      mammals have equal numbers of ligands and receptors. To date, the ligand-receptor
      relationships of teleost Rln/Insl peptides and their receptors have largely
      remained unexplored. Here, we use selection analyses based on sequence data from
      5 teleosts and qPCR expression data from zebrafish to explore possible ligand
      receptor pairings in teleosts. We find support for the hypothesis that, with the
      exception of RLN, which has undergone strong positive selection in mammalian
      lineages, the ligand and receptor genes shared between mammals and teleosts
      appear to have similar pairings. On the other hand, the teleost-specific
      receptors show evidence of subfunctionalization. Overall, this study underscores
      the complexity of RLN/INSL and RXFP ligand-receptor interactions in teleosts and
      establishes theoretical background for further experimental work in nonmammals.

PMID- 23008800
TI  - Phylogeographic Diversity of the Lower Central American Cichlid Andinoacara
      coeruleopunctatus (Cichlidae).
AB  - It is well appreciated that historical and ecological processes are important
      determinates of freshwater biogeographic assemblages. Phylogeography can
      potentially lend important insights into the relative contribution of historical
      processes in biogeography. However, the extent that phylogeography reflects
      historical patterns of drainage connection may depend in large part on the
      dispersal capability of the species. Here, we test the hypothesis that due to
      their relatively greater dispersal capabilities, the neotropical cichlid species
      Andinoacara coeruleopunctatus will display a phylogeographic pattern that differs
      from previously described biogeographic assemblages in this important region.
      Based on an analysis of 318 individuals using mtDNA ATPase 6/8 sequence and
      restriction fragment length polymorphism data, we found eight distinct clades
      that are closely associated with biogeographic patterns. The branching patterns
      among the clades and a Bayesian clock analysis suggest a relatively rapid
      colonization and diversification among drainages in the emergent Isthmus of
      Panama followed by the coalescing of some drainages due to historical
      connections. We also present evidence for extensive cross-cordillera sharing of
      clades in central Panama and the Canal region. Our results suggest that
      contemporary phylogeographic patterns and diversification in Lower Central
      American fishes reflect an interaction of historical drainage connections,
      dispersal, and demographic processes.

PMID- 23008799
TI  - In with the old, in with the new: the promiscuity of the duplication process
      engenders diverse pathways for novel gene creation.
AB  - The gene duplication process has exhibited far greater promiscuity in the
      creation of paralogs with novel exon-intron structures than anticipated even by
      Ohno. In this paper I explore the history of the field, from the neo-Darwinian
      synthesis through Ohno's formulation of the canonical model for the evolution of
      gene duplicates and culminating in the present genomic era. I delineate the major
      tenets of Ohno's model and discuss its failure to encapsulate the full complexity
      of the duplication process as revealed in the era of genomics. I discuss the
      diverse classes of paralogs originating from both DNA- and RNA-mediated
      duplication events and their evolutionary potential for assuming radically
      altered functions, as well as the degree to which they can function unconstrained
      from the pressure of gene conversion. Lastly, I explore theoretical population
      genetic considerations of how the effective population size (N(e)) of a species
      may influence the probability of emergence of genes with radically altered
      functions.

PMID- 23008801
TI  - Purifying Selection Bias against Microsatellites in Gene Rich Segmental
      Duplications in the Rice Genome.
AB  - Little data is available on microsatellite dynamics in the duplicated regions of
      the rice genome, even though efforts have been made in the past to align genome
      sequences of its two sub-species. Based on the coordinates of duplicated
      sequences in the indica genome as available in the public domain, we identified
      microsatellites in these regions. CCG and GAAAA repeats occurred most frequently.
      In all, 259 microsatellites could be identified in the duplicated sequences using
      the criteria of minimum 90% alignability spread over a minimum of 1 Kb sequence.
      More than 25% of the repeats in duplicated regions occurred in the genic
      sequences. Only 45 (17%) of these 259 microsatellites were found conserved in the
      duplicated paralogues. Among these repeats, 40% maintained both sequence and
      length conservation. The effect of mutability of nearby regions could also be
      clearly seen in microsatellite regions. The overall purpose of this study was to
      investigate, whether microsatellites follow an independent course of evolutionary
      dynamics subsequent to events like genome reshuffling that simply drives these
      elements to different locations in the genome. To the best of our knowledge, this
      is the first comprehensive analysis of microsatellite conservation in the
      duplicated regions of any genome.

PMID- 23008802
TI  - Development of antimetastatic drugs by targeting tumor sialic acids.
AB  - One-third of all cancer categories in clinics have a high incidence of neoplasm
      metastasis. Neoplasm metastasis is one of the leading causes of cancer deaths.
      However, the prevailing therapeutic approach to this pathogenic process is
      presently unsatisfactory. Paradoxically to our efforts and expectations, except
      for some antibodies, no obvious improvements and therapeutic benefits in
      currently used drugs have been achieved until now. Therapeutic benefits in late
      stage or elderly cancer patients are especially poor and useless. One of the
      reasons for this, we would guess, is the lack of therapeutic targets specifically
      related to neoplasm metastasis. In order to enhance the therapeutic efficacy, the
      development of antimetastatic drugs transcending from current drug-screening
      pathways is urgently needed. Antimetastatic drugs targeting aberrantly sialylated
      in tumors have evolved for about a quarter of a century and might be a future
      therapeutic option other than the currently utilized antimetastatic drugs, such
      as antivascular and MMP inhibitors. Since neoplasm tissues often manifest high
      levels of sialic acids and sialyl antigens or glycoligands, some types of sialic
      acid analogue, such as N-glycolylneuraminic acid (Nau5Gc), occurred in most tumor
      tissues which is normally absent in most humans. Consequently, more attention is
      needed to work with new therapeutic approaches to target these changes. This
      review addresses and discusses the latest six types of therapeutic approaches
      targeting sialic acids in metastatic tissues.

PMID- 23008803
TI  - Fused Thiopyrano[2,3-d]thiazole Derivatives as Potential Anticancer Agents.
AB  - rel-(5aR,11bR)-3,5a,6,11b-tetrahydro-2H,5H-chromeno[4',3':4,5]thiopyrano[2,3
      d][1,3]thiazol-2-ones formed by the stereoselective Knoevenagel-hetero-Diels
      Alder reaction were functionalized at the nitrogen in position 3 via reactions of
      alkylation, cyanoethylation, and acylation. The synthesized compounds were
      evaluated for their anticancer activity in NCI60 cell lines. Among the tested
      compounds, 3f was found to be the most active candidate with the greatest
      influence on leukemia, non-small cell lung cancer, colon cancer, CNS cancer,
      melanoma, prostate cancer, and breast cancer subpanel cell lines with GI(50)
      values over a range of 0.37-0.67 MUM.

PMID- 23008804
TI  - Design, Synthesis, and Antitumor Evaluation of Novel Pyrazolo[3,4-d]pyrimidine
      Derivatives.
AB  - A new series of pyrazolo[3,4-d]pyrimidines has been synthesized. The new
      compounds were tested for their antitumor activity on 60 different cell lines,
      and some of the compounds were found to have potent antitumor activity. In
      particular, 2-hydroxybenzaldehyde [1-(4-chlorophenyl)-3-methyl-1H-pyrazolo-[3,4
      d]pyrimidin-4-yl]hydrazone (VIIa) was found to be the most effective among the
      other derivatives, showing IC50 values of 0.326 to 4.31 MUM on 57 different cell
      lines.

PMID- 23008805
TI  - Improvement of the Prediction Power of the CoMFA and CoMSIA Models on Histamine
      H3 Antagonists by Different Variable Selection Methods.
AB  - The aim of this study is to enhance the predictivity power of CoMFA and CoMSIA
      models by means of different variable selection algorithms. The genetic algorithm
      (GA), successive projection algorithm (SPA), stepwise multiple linear regression
      (SW-MLR), and the enhanced replacement method (ERM) were used and tested as
      variable selection algorithms. Then, the selected variables were used to generate
      a simple and predictive model by the multilinear regression algorithm. A set of
      74 histamine H(3) antagonists were split into 40 compounds as a training set, and
      17 compounds as a test set, by the Kennard-Stone algorithm. Before splitting the
      data, 17 compounds were randomly selected from the pool of the whole data set as
      an evaluation set without any supervision, pretreatment, or visual inspection.
      Among applied variable selection algorithms, ERM had noticeable improvement on
      the statistical parameters. The r(2) values of training, test, and evaluation
      sets for the ERM-MLR model using CoMFA fields were 0.9560, 0.8630, and 0.8460 and
      using the CoMSIA fields were 0.9800, 0.8521, and 0.9080, respectively. In this
      study, the principles of organization for economic cooperation and development
      (OECD) for regulatory acceptability of QSARs are considered.

PMID- 23008806
TI  - Development and Validation of a Stability-Indicating RP-HPLC Method for the
      Quantitative Analysis of Anagrelide Hydrochloride.
AB  - A simple, rapid, and stability-indicating reverse-phase liquid chromatographic
      assay method was developed for Anagrelide Hydrochloride (ANG) in the presence of
      its degradation products generated from forced decomposition studies. The HPLC
      separation was achieved on a C18 Inertsil column (250 mm * 4.6 mm i.d. particle
      size is 5 MUm), using solution A, a mixture of 0.03 M potassium di-hydrogen
      phosphate pH-adjusted to 3.0 using ortho-phosphoric acid (buffer): methanol:
      acetonitrile (90:5:5, v/v/v), and solution B, which contains a mixture of buffer:
      acetonitrile (10:90, v/v). The UV detector was operated at 251 nm while column
      temperature was maintained at 40 degrees C, and the gradient program had the flow
      rate of 1.0 mL min(-1). The developed method was validated as per ICH guidelines
      with respect to specificity, linearity, precision, accuracy, robustness, and
      limit of quantification. The method was found to be simple, specific, precise,
      accurate, and reproducible. Selectivity was validated by subjecting the stock
      solution of ANG to acidic, basic, photolysis, oxidative, and thermal degradation.
      The calibration curve was found to be linear in the concentration range of 0.05
      152 MUg mL(-1) (R(2) = 0.9991). The peaks of degradation products did not
      interfere with that of pure ANG. The utility of the developed method was examined
      by analyzing the tablets containing ANG.

PMID- 23008807
TI  - Simultaneous Estimation of Amlodipine Besylate and Indapamide in a Pharmaceutical
      Formulation by a High Performance Liquid Chromatographic (RP-HPLC) Method.
AB  - An isocratic reversed-phase liquid chromatograpic assay method was developed for
      the quantitative determination of amlodipine besylate (AML) and indapamide (IND)
      in combined dosage form. A Brownlee C-18, 5 MUm column with a mobile phase
      containing 0.02 M potassium dihydrogen phosphate-methanol (30+70, v/v) total pH
      adjusted to 3 using o-phosphoric acid was used. The flow rate was 1.0 mL min(-1)
      and effluents were monitored at 242 nm. The retention times of amlodipine
      besylate and indapamide were 5.9 min and 3.6 min, respectively. The proposed
      method was validated with respect to linearity, accuracy, precision, and
      robustness. The method was successfully applied to the estimation of amlodipine
      besylate and indapamide in combined tablet dosage forms.

PMID- 23008808
TI  - A Rapid, Stability-Indicating RP-HPLC Method for the Simultaneous Determination
      of Formoterol Fumarate, Tiotropium Bromide, and Ciclesonide in a Pulmonary Drug
      Product.
AB  - A stability-indicating reversed-phase high performance liquid chromatography (RP
      HPLC) method was developed for the simultaneous determination of Formoterol
      fumarate (FOR), Tiotropium bromide (TRI), and Ciclesonide (CLS) in a pulmonary
      drug product. The desired chromatographic separation was achieved on the Zorbax
      SB C8, 5 MUm (150 * 4.6 mm) column, using gradient elution at 230 nm detector
      wavelength. The optimized mobile phase consisted of a 0.2 % v/v perchloric acid
      as solvent-A and acetonitrile as solvent-B. The developed method separated FOR,
      TRI, and CLS in the presence of its five unknown degradation products within 10
      minutes. The stability-indicating capability was established by forced
      degradation experiments and the separation of unknown degradation products. The
      developed RP-HPLC method was validated according to the International Conference
      on Harmonization (ICH) guidelines. This validated method was applied for the
      simultaneous estimation of FOR, TRI, and CLS in commercially available
      Triohale((r)) pMDI (Pressurized Metered-Dose Inhaler) samples. Furthermore, this
      method can be extended for individual estimation of FOR, TRI, and CLS in various
      commercially available pulmonary dosage forms.

PMID- 23008809
TI  - Identification and characterization of potential impurities in raloxifene
      hydrochloride.
AB  - During the synthesis of the bulk drug Raloxifene hydrochloride, eight impurities
      were observed, four of which were found to be new. All of the impurities were
      detected using the gradient high performance liquid chromatographic (HPLC)
      method, whose area percentages ranged from 0.05 to 0.1%. LCMS was performed to
      identify the mass number of these impurities, and a systematic study was carried
      out to characterize them. These impurities were synthesized and characterized by
      spectral data, subjected to co-injection in HPLC, and were found to be matching
      with the impurities present in the sample. Based on their spectral data (IR, NMR,
      and Mass), these impurities were characterized as Raloxifene-N-Oxide [Impurity:
      1]; EP impurity A [Impurity: 2]; EP impurity B [Impurity: 3]; Raloxifene Dimer
      [Impurity: 4]; HABT (6-Acetoxy-2-[4-hydroxyphenyl]-1-benzothiophene or 6-Hydroxy
      2-[4-acetoxyphenyl]-1-benzothiophene) [Impurity: 5]; PEBE (Methyl[4-[2-(piperidin
      1-yl)ethoxy]]benzoate) [Impurity: 6]; HHBA (1-[6-hydroxy-2-(4-hydroxyphenyl)-1
      benzothiophen-3-yl]ethanone) [Impurity: 7]; 7-MARLF (7-Acetyl-[6-hydroxy-2-(4
      hydroxyphenyl)-1-benzothiophen-3-yl][4-[2-(piperidin-1-yl)ethoxy]phenyl
      methanone) [Impurity: 8]; of which impurities 5-8 are reported for the first
      time.

PMID- 23008810
TI  - Stability-Indicating RP-HPLC Method for the Simultaneous Determination of
      Prazosin, Terazosin, and Doxazosin in Pharmaceutical Formulations.
AB  - The current study was carried out with an attempt to separate similarly
      structured title drugs by liquid chromatography. Spectrophotometric techniques
      were generally insufficient under these conditions because of the spectral
      overlapping of drugs with similar functional groups. The pharmaceutical drugs
      prazosin, terazosin, and doxazosin contain the same parent quinazoline nucleus,
      thus making it especially difficult to separate the former two drugs because of
      their very similar structures. A simple and sensitive method for the routine
      determination of these drugs in pharmaceutical formulations was attempted. We
      found that the mobile phase consisting of A: ACN-diethylamine (0.05 ml), B:
      methanol, and C: 10 mM Ammonium acetate separated these drugs effectively.
      Separations were carried out on a new Kromasil C18 column (250 * 4.6 mm, 5.0 MUm)
      at 254 nm wavelength. The calibration curve was found to be linear in the range
      of 2-500 MUg/ml. The stated method was then validated in terms of specificity,
      linearity, precision, and accuracy. Additionally, the proposed method reduced the
      duration of the analysis.

PMID- 23008811
TI  - Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl
      Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass
      Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation.
AB  - A new method for the simultaneous determination of celecoxib, erlotinib, and its
      active metabolite desmethyl-erlotinib (OSI-420) in rat plasma, by liquid
      chromatography/tandem mass spectrometry with positive/negative ion-switching
      electrospray ionization mode, was developed and validated. Protein precipitation
      with methanol was selected as the method for preparing the samples. The analytes
      were separated on a reverse-phase C(18) column (50mm*4.6mm i.d., 3MU) using
      methanol: 2 mM ammonium acetate buffer, and pH 4.0 as the mobile phase at a flow
      rate 0.8 mL/min. Sitagliptin and Efervirenz were used as the internal standards
      for quantification. The determination was carried out on a Theremo Finnigan
      Quantam ultra triple-quadrupole mass spectrometer, operated in selected reaction
      monitoring (SRM) mode using the following transitions monitored simultaneously:
      positive m/z 394.5->278.1 for erlotinib, m/z 380.3->278.1 for desmethyl erlotinib
      (OSI-420), and negative m/z -380.1-> -316.3 for celecoxib. The limits of
      quantification (LOQs) were 1.5 ng/mL for Celecoxib, erlotinib, and OSI-420.
      Within- and between-day accuracy and precision of the validated method were
      within the acceptable limits of < 15% at all concentrations. The quantitation
      method was successfully applied for the simultaneous estimation of celecoxib,
      erlotinib, and desmethyl erlotinib in a pharmacokinetic study in Wistar rats.

PMID- 23008812
TI  - Chronic inhibition of central Angiotensin-converting enzyme ameliorates
      colchicine-induced memory impairment in mice.
AB  - Preclinical and clinical studies indicated involvement of the central renin
      angiotensin system (RAS) in memory functions. However, the role of central
      angiotensin-converting enzyme (ACE) in memory function is still unclear. The
      present study investigated the involvement of central ACE in colchicine-induced
      memory impairment in the context of cholinergic function and oxidative stress.
      Memory impairment was induced by intracerebral colchicine administration in mice.
      The ACE inhibitor, perindopril (0.05 and 0.1 mg/kg/day), was administered orally
      for 14 days. Memory function was evaluated by the Morris water maze (MWM) test
      from the 14(th) day on after colchicine injection. Donepezil was used as a
      standard. Parameters of oxidative stress and cholinergic function, ACE activity
      in serum and the brain were estimated after the completion of behavioral studies.
      Colchicine caused memory impairment as revealed by no significant change in
      latency to reach a hidden platform in the MWM test. Furthermore, there was a
      significant increase in MDA, ROS, and nitrite levels with a reduction in GSH
      level and acetylcholinesterase (AChE) activity in the brain of colchicine-treated
      mice. Colchicine significantly increased brain ACE activity without affecting
      serum ACE. Donepezil prevented colchicine-induced memory impairment in mice. The
      antidementic effect of perindopril may be attributed to reduced oxidative stress
      and improvement in cholinergic function. Moreover, the elevated brain ACE
      activity was also inhibited by perindopril. The study showed that central ACE
      plays an important role in colchicine-induced memory deficit, corroborating a
      number of studies that show that treatment with ACE inhibitors could be
      neuroprotective.

PMID- 23008813
TI  - Comparative study of the cytotoxicity and genotoxicity of alpha- and Beta
      asarone.
AB  - The cytotoxicity of alpha- and beta-asarone was investigated with the BrdU assay
      in HepG2-cells. Alpha-asarone was found to be more toxic than beta-asarone after
      24 hours of treatment. Investigation of the genotoxicity using the micronucleus
      assay in the HepG2-cell system showed that only after metabolic activation by a
      liver microsomal preparation, beta-asarone was able to induce micronuclei at
      concentrations higher than 50 MUg/mL.

PMID- 23008814
TI  - Effects of Calendula Essential Oil-Based Cream on Biochemical Parameters of Skin
      of Albino Rats against Ultraviolet B Radiation.
AB  - Reactive oxygen species (ROS) generated from UV-B radiation have the capacity to
      cause oxidative decomposition which leads to the formation of toxic components as
      well as lipid peroxidation. Considering this fact, the present study was
      performed to evaluate the effect of a cream (O/W) containing the essential oil of
      Calendula officinalis on biochemical parameters of the skin of albino rats
      against UV-B radiation. The fingerprint analysis of Calendula essential oil was
      performed by HPLC with special reference to 1,8-cineole and alpha-pinene. The
      results indicated that the treatment with creams containing 4% and 5% of
      Calendula essential oil caused a significant decrease in the malonyldialdehyde
      level, whereas the levels of catalase, glutathione, superoxide dismutase,
      ascorbic acid, and the total protein level were significantly increased after 1
      month of daily irradiation and treatment when compared to untreated control
      groups. The results suggest that the cutaneous application of the essential oil
      of Calendula prevents UV-B-induced alterations in the level of antioxidants in
      skin tissue.

PMID- 23008815
TI  - Anti-Inflammatory and Antinociceptive Activities of a Hydroethanolic Extract of
      Tamarindus indica Leaves.
AB  - The present study aimed to investigate the anti-inflammatory and anti-nociceptive
      potential of a hydroethanolic extract of Tamarindus indica L. leaves (HTI) along
      with its possible mode of action. The anti-inflammatory activity of HTI was
      estimated by carrageenan-induced hind paw oedema in male Wistar albino rats.
      Furthermore, HTI was assessed to determine its effects on membrane stabilization.
      The antinociceptive action was determined by acetic acid-induced writhing, tail
      flick, and the hot plate model. Oral administration of HTI at the dose of 500,
      750, and 1000 mg/kg body weight produced significant (P< 0.01) anti-inflammatory
      as well as antinociceptive actions in a dose-dependent manner. Among all tested
      doses, 1000 mg/kg, p. o. reduced carrageenan-induced rat paw oedema at 1, 2, 3,
      and 4 h. Moreover, the 1000 mg/kg dose exhibited maximum percentage inhibition of
      acetic acid-induced writhing (48.9%), whereas standard drug diclofenac (25 mg/kg,
      p. o.) showed maximum inhibition (50.9%) of writhing. In the hot plate model, HTI
      (1000 mg/kg, orally) increased mean basal reaction time after 120 min (7.12+/
      0.05 sec). In the tail flick model, HTI increased the maximum percentage of
      latency (36.06%), whereas the standard drug pethidine (4 mg/kg,
      intraperitoneally) showed maximum percentage of latency (43.85%) after 60 min.
      The findings of the present study supported anti-inflammatory and antinociceptive
      claims of T. indica as were mentioned in Indian traditional and folklore
      practices.

PMID- 23008817
TI  - Impact of Adjunctive Therapy with Chlorellav ulgaris Extract on Antioxidant
      Status, Pulmonary Function, and Clinical Symptoms of Patients with Obstructive
      Pulmonary Diseases.
AB  - This present trial investigated the efficacy of supplementation with Chlorella
      vulgaris, a bioactive microalga rich in macro- and micronutrients, in the
      improvement of biochemical and clinical symptoms in patients with obstructive
      pulmonary disorders. Ninety-seven patients with chronic obstructive pulmonary
      disease (COPD) or asthma who were under conventional treatment regimens were
      randomly assigned to C. vulgaris extract (CVE) (n=48; 2700 mg/day) or no
      adjunctive therapy (n=49) for eight weeks. Serum levels of antioxidants along
      with spirometric parameters and clinical symptoms were evaluated pre- and post
      trial. The magnitude of increases in the concentrations of glutathione, vitamin
      E, and vitamin C, and activities of glutathione peroxidase, catalase, and
      superoxide dismutase enzymes were all significantly greater in the CVE vs.
      control group (p<0.05). In spite of increases, none of the assessed spirometric
      parameters (FVC, FEV1, FEV1/FVC, and FEF(25-75%)) did significantly differ by the
      end of the trial in the study groups, apart from a significant elevation of FEV1
      in the control group (p=0.03). The frequency of coughing, shortness of breath,
      wheezing, and sputum brought up were all significantly reduced in both CVE and
      control groups (p<0.05). The rate of improvement for sputum brought up and
      wheezing were significantly greater in the CVE group compared to the control
      group (p<0.05). Although CVE was found to ameliorate serum antioxidant status,
      its supplementation was not associated with any bronchodilatory activity. The
      results of the present trial do not support any clinical efficacy for CVE in
      patients with obstructive pulmonary disorders.

PMID- 23008816
TI  - The Gastroprotective Role of Acanthus ilicifolius - A Study to Unravel the
      Underlying Mechanism of Anti-Ulcer Activity.
AB  - Acanthus ilicifolius (Acanthaceae), a mangrove medicinal plant, is widely used by
      the local inhabitants of the Sundarbans (India) to treat a variety of diseases.
      As a part of our continued search for novel bioactive products from mangrove
      medicinal plants, we were able to document the anti-inflammatory effects of this
      plant. In the present study, we have performed a detailed evaluation of the
      gastroprotective activity of the methanolic extract of Acanthus ilicifolius using
      different models of gastric ulceration. Unlike the conventional non-steroidal
      anti-inflammatory drugs, a methanolic extract of Acanthus ilicifolius leaves
      (MEAL) possessing significant anti-inflammatory properties, as revealed from our
      previous studies displayed in rats in dosages of 200 mg and 400 mg/kg BW after
      intraperitoneal administration, showed significant protective activity (anti
      ulcer activity) against the gastric lesions induced by aspirin, indomethacin,
      stress, ethanol, and pylorus ligation. In pylorus-ligated rats, administration of
      Methanolic extract of Acanthus ilicifolius leaves (MEAL) significantly decreased
      gastric volume, acidity, and peptic activity. Moreover, pre-treatment with MEAL
      significantly restored the levels of reduced glutathione (GSH) and the
      antioxidant enzyme superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GPX), along with significant inhibition of both lipid peroxidation
      and myeloperoxidase (MPO) activity in pylorus-ligated animals. Ulceration induced
      with ethanol was significantly inhibited with MEAL, and the extract also resulted
      in the reduction of both lipid peroxidation and myeloperoxidase activity.
      Furthermore, in this experimental model, administration of MEAL improved the
      activities of SOD, CAT, GSH, and GPX. A similar pattern of action was also
      noticed in cold-restraint stress-induced (CRS) ulceration, where MEAL pre
      treatment inhibited CRS-induced ulceration, improved the status of antioxidant
      enzymes, and also reduced the level of lipid peroxides. These results suggest
      that extracts of the leaves of Acanthus ilicifolius may exhibit anti-ulcer
      activities additional to the anti-inflammatory properties.

PMID- 23008818
TI  - Formulation and optimization of clotrimazole-loaded proniosomal gel using 3(2)
      factorial design.
AB  - The main aim of the study was to develop and statistically optimize the
      proniosomal gel for enhanced transdermal delivery using 3(2) factorial designs to
      investigate the influence of both non-ionic surfactant and cholesterol to
      maximize the entrapment efficiency and flux. The concentration of non-ionic
      surfactant and cholesterol were taken as independent variables, while entrapment
      efficiency and flux were taken as dependent variables. The study showed that the
      entrapment efficiency depends on both cholesterol and surfactant, whereas
      permeation flux depends only on the surfactant. Proniosomal gel showed a
      significantly enhanced drug permeation through the skin, with an enhancement
      ratio 3.81+/-1.85 when compared to the drug solution. Comparative evaluation of
      permeation studies and the in vitro release study of optimized proniosomal gel
      (F5) with that of marketed gel and carbopol gel showed that the penetration of
      the optimized formulation was enhanced 1.75 times in comparison with that of the
      marketed formulation, and the release was in a controlled manner. Similarly, the
      anticandidial activity showed a significantly higher activity (p<0.05) than the
      marketed and carbopol gel. This may be due to the enhanced penetration of noisome
      containing drug through the fungal cell wall, inhibiting the ergo sterol
      synthesis, thereby causing the fungal cell death due to the presence of
      penetration enhancer. The stability study at two different temperatures (30 +/- 2
      degrees C and 4 +/- 2 degrees C) confirmed that the formulations were stable even
      at the end of 45 days. Hence, proniosomal gel is an efficient carrier for the
      delivery of clotrimazole, thereby prolonging the action.

PMID- 23008819
TI  - Nanostructured Lipid Carriers (NLC)-Based Gel for the Topical Delivery of
      Aceclofenac: Preparation, Characterization, and In Vivo Evaluation.
AB  - The aim of this study was to prepare nanostructured lipid carriers (NLC)-based
      topical gel of aceclofenac for the treatment of inflammation and allied
      conditions. Stearic acid as the solid lipid, oleic acid as the liquid lipid,
      pluronic F68 as the surfactant, and phospholipon 90G as the co-surfactant were
      used. NLCs were prepared by melt-emulsification, low-temperature solidification,
      and high-speed homogenization methods. Characterization of the NLC dispersion was
      carried out through particle size analysis, scanning electron microscopy (SEM),
      differential scanning calorimetry (DSC), and an in vitro release study. The anti
      inflammatory effect of the NLC gel was assessed by the rat paw edema technique
      and compared to marketed aceclofenac gel. The NLC dispersions exhibited d(90%)
      between 233 nm and 286 nm. All of the NLC showed high entrapment efficiency
      ranging from 67% to 82%. The particle size of NLC was further confirmed by the
      SEM study. The result of DSC showed that aceclofenac was dispersed in NLC in an
      amorphous state. Both the entrapment and release rate were affected by the
      percentage of oleic acid, but the method of preparation affected only the
      entrapment efficiency. The nanoparticulate dispersion was suitably gelled and
      assessed for in vitro permeation. Finally, NLC-based gels were found to possess
      superior (almost double) the anti-inflammatory activity compared to the marketed
      product. The anti-inflammatory activity of NLC gel showed a rapid onset of
      action, as well as a prolonged duration of action as compared with the marketed
      gel.

PMID- 23008820
TI  - Occlusive and non-occlusive application of microemulsion for transdermal delivery
      of progesterone: mechanistic studies.
AB  - This work evaluated the occlusive versus non-occlusive application of
      microemulsion (ME) for the transdermal delivery of progesterone. The mechanisms
      of enhanced skin penetration were investigated. ME comprised of oleic acid, Tween
      80, propylene glycol, and water, was used neat or with ethanol as a volatile
      cosurfactant. The ME formulations enhanced progesterone transdermal flux compared
      to the saturated drug solution in 14% aqueous propylene glycol (control). Ethanol
      containing ME (EME) was better than the ethanol-free system (EFME). Open
      application of EFME produced a marginal reduction in flux compared to occlusive
      application. For EME, open application reduced the flux by 26-28% with the flux
      remaining significantly higher than that obtained with EFME. The mechanistic
      studies revealed synergism between ethanol and EFME with EME, producing greater
      flux than the sum of fluxes obtained from 40% ethanol in water and EFME.
      Penetration enhancement and supersaturation played a role in enhanced transdermal
      delivery, but other mechanisms were also possible. This study thus introduced EME
      as a transdermal delivery system for progesterone with good potential for open
      application as a spray.

PMID- 23008821
TI  - Development and characterization of pharmacokinetic parameters of fast-dissolving
      films containing levocetirizine.
AB  - A fast-dissolving film containing levocetirizine, a non-sedative antihistamine
      drug, was developed using pullulan, xanthan gum, propylene glycol, and tween 80
      as the base materials. The drug content of the prepared films was within an
      acceptable limit as prescribed by the USP. The film exhibited excellent stability
      for four months when stored at 40  degrees C and 75% humidity. In vitro
      dissolution studies suggested a rapid disintegration, in which most of
      levocetirizine (93.54 +/- 3.9%) dissolved within 90 seconds after insertion into
      the medium. Subsequently, Sprague-Dawley rats were used to compare the
      pharmacokinetic properties of the film preparation administered to the oral
      cavity, to those with oral administration of the pure drug solution. The
      pharmacokinetic parameters were similar between the two groups in which AUC(0-t)
      (ng h/ml), AUC(0-infinity) (ng h/ml) C(max) (ng/ml), T(max) (min), K(el) (h(-1)),
      and t(1/2) (h) of the reference were 452.033 +/- 43.68, 465.78 +/- 48.16, 237.16
      +/- 19.87, 30, 0.453 +/- 0.051, and 1.536 +/- 0.118, respectively, for the film
      formulation 447.233 +/- 46.24, 458.22 +/- 46.74, 233.32 +/- 17.19, 30, 0.464 +/-
      0.060, and 1.496 +/- 0.293, respectively. These results suggest that the present
      levocetirizine containing fast-dissolving film is likely to become one of the
      choices to treat different allergic conditions.

PMID- 23008822
TI  - [Breast care nurse. A new specialist in the multidisciplinary care of breast
      cancer patients].
AB  - The uniform European structure and professional standards for high quality breast
      cancer care were established in conjunction with the European Organisation for
      Research and Treatment, the European Society of Mastology and the European Breast
      Cancer Coalition with the support of the European Parliament. Well-prepared
      professional teams including a new member called the breast care nurse serve as
      ground for special breast cancer centers with international accreditation that
      provide modern, evidence based, patient centered multidisciplinary oncological
      care. The responsibilities of the new qualified professional staff member include
      the psycho-social support of the patient and carers from the moment of diagnosis
      throughout the whole oncological treatment, the fostering of delivering
      information and communication between patients and specialists. As a result of
      the curriculum founded by the European Oncology Nursing Society, breast care
      nurses have become key members of the practice of holistic breast cancer care in
      countries where the European recommendations have already been implemented.
      Considering the expected rearrangement of national oncological care, the new sub
      specialty is outlined for the first time in the light of the experiences gained
      at the National Institute of Oncology, Budapest, a comprehensive cancer center.

PMID- 23008823
TI  - [Supportive care during chemotherapy for lung cancer in daily practice].
AB  - Active oncotherapy, combination chemotherapy of lung cancer is accompanied with
      many side effects which may impair patients' quality of life and compromise the
      effectiveness of chemotherapy. Most side effects of chemotherapy are preventable
      or treatable with optimal supportive care which enhances success in patient care
      and treatment. The aim of this review is to summarize the most important
      conditions that may be associated with combined chemotherapy of lung cancer from
      the practical point of view.

PMID- 23008824
TI  - [Use of angioneogenesis inhibitor monoclonal antibody following standard therapy
      in recurrent or progressive glioblastoma multiforme].
AB  - Glioblastoma is a brain tumor with poor prognosis in the therapy of which
      operation, postoperative temozolomide sensitized radiochemotherapy followed by
      temozolomide monotherapy offer the best chances. Administration of temozolomide
      is also recommended in relapse if the patient is naive to this treatment. In
      recurrent or progressive glioblastoma following the above therapy, several
      biological therapeutic agents were tested, out of which the angiogenesis
      inhibitor bevacizumab has been approved by FDA (and similar authority of several
      other countries). Bevacizumab monotherapy resulted in objective tumor response in
      28.2%, the median of progression-free survival was 4.2 (2.9-5.8) months, the
      median of overall survival was 9.2 (8.2-10.7) months. When combined with
      irinotecan, these results were 37.8%, 5.6 (4.4-6.2) and 8.7 (7.8-10.9) months,
      respectively. Adverse events were known from the use of bevacizumab in other
      indications, symptoms affecting the central nervous system were mild, i.e. the
      therapy proved to be not only effective but safe as well. Reduction of edema
      provided further advantage. In Hungary the product is available for "off-label"
      use only through a fairness request process.

PMID- 23008826
TI  - [Role of MRI in determining the therapy of rectal cancer].
AB  - Over the past decade, significant progress has been made in the management of
      rectal cancer. Advances in surgical technique and adjuvant therapies have led to
      significant improvements in outcome for some patients. The advances in
      preoperative therapies have led to the need for an accurate preoperative staging
      technique to select those patients who are expected to benefit from these
      interventions without subjecting others to unnecessary treatment. Performing
      neoadjuvant therapy knowledge of the relationship of the tumor to the
      circumferential resection margin is of importance. In Hungary, respecting
      European guidelines, the high resolution magnetic resonance imaging is mandatory
      in the staging of rectal cancer, and in early rectal cancer transrectal
      endosonography has a complementary role. The current role of multidetector
      computer tomography is for detecting distant metastasis and in local tumor
      staging of advanced cancers.

PMID- 23008825
TI  - [Complete pathologic remission after preoperative high-dose brachytherapy in
      patients with operable cervical cancer: preliminary results of a prospective
      randomized study].
AB  - The purpose of the study was a preliminary evaluation of the efficacy of
      preoperative intracavitary high-dose-rate brachytherapy (HDR BT) in sterilization
      of the specimen of operable cervical cancer patients enrolled into a prospective,
      randomized study. Between 2005 and 2010, 100 operable cervical cancer patients of
      FIGO stage I/A2 (n=4), I/B1 (n=51), I/B2 (n=19), IIA (n=17), and proximal II/B
      (n=9) were randomized in two arms: in arm "A" (n=50) allocated treatment was 2x8
      Gy preoperative intracavitary HDR BT followed by radical surgery, in arm "B" (n=
      50) no preoperative treatment was given before the planned radical Wertheim
      hysterectomy. The rates of pathologic complete remission (pCR) were compared
      using the Fisher-exact test. In arm "A" 41 patients (82%), in arm "B" 42 patients
      (84%) underwent radical hysterectomy. The rate of pCR after preoperative BT was
      26.8% (11/41), while in the control group the specimen was free of tumor in 7.1%
      (3/42; p=0.0204). Preoperative HDR BT for cervical cancer patients significantly
      increases the rate of pathologically tumor-free specimens. Longer follow-up is
      needed to evaluate the impact of pCR on local tumor control and survival. Our
      preliminary results support further enrollment of patients into our randomized
      clinical trial.

PMID- 23008827
TI  - [Smoking: a prognostic factor of lung cancer survival].
AB  - Eighty % of lung cancer cases are attributable to smoking. There have been
      several publications concerning the prognostic factor role of smoking in lung
      cancer survival. Our research proposed four aims: 1) to gather more concise data
      about the smoking habits of lung cancer patients; 2) to demonstrate the
      relationship between the quantitative indicator pack year index (PYI) of smoking
      history and survival; 3) to test the hypothesis that smoking is not only a risk
      factor, but also a prognostic factor in lung cancer survival; and 4) to assess
      the survival advantage of smoking cessation at the time of diagnosis among lung
      cancer patients. We employed a questionnaire based prospective cohort design of
      lung cancer patients diagnosed in Budapest, 2009. We collected data on the method
      of cancer detection, cell types, stage, treatment, comorbidities and smoking
      habits at baseline. Follow-up questionnaires were completed to document changes
      (survival, smoking habits) every six months. Our sample included 929 patients
      (521 males and 408 females). The majority had a history of smoking (79%),
      including 68% current and 32% former smokers. The average PYI was 33. Fifty-seven
      % of current smokers quit at the time of lung cancer diagnosis (3% relapsed) and
      43% continued smoking. The 30-month survival probabilities were found to be as
      follows: smokers who had PYI<=39: 44%; PYI>=40: 35%. PYI <=39 vs. >=40 [HR=1.26,
      95% CI 1.02 1.64; p=0.045]. The 30-month survival proved to be significantly
      better for those patients who quit at the time of diagnosis (quitters: 54% vs.
      continuous smokers: 42% [HR=1.29, 95% CI 1.12 1.78; p<0.001]). The benefit of
      quitting smoking was observed both in the surgically resected and the not
      resected group. Our results demonstrate that smoking is not only a risk factor
      for lung cancer, but also a strong prognostic factor of survival at 30 months
      after diagnosis. Survival is also significantly influenced by the smoking history
      (PYI). It is markedly important for smoking patients to quit smoking at the time
      of diagnosis.

PMID- 23008828
TI  - [Patient positioning using in-room kV CT for image-guided radiotherapy (IGRT) of
      prostate cancer].
AB  - The purpose of the study was to evaluate accuracy of patients' set up verified by
      kV CT-on-rails system and compare automatic and manual image registration of
      planning and verification kVCT-s. Between January 2001 and March 2011, at ten
      patients with prostate cancer the clinical target volumes (CTVs) for prostate
      (CTV-PROS), and prostate plus caudal 1 cm of seminal vesicles (CTV-PVS) with or
      without pelvic lymph node region were contoured on the treatment planning CT,
      according to risk category of the patient. Planning target volumes (PTVs) were
      created with 1 cm margin extended around the CTVs in each direction. The
      isocentre was marked on the skin with three radiopaque markers. After the set up,
      treatment couch with the patient was turned by 180 degree and images were
      acquired of the region of the isocentre with a kV helical CT-on-rails system
      (treatment CT). An image registration software was used to co-register planning
      and treatment CT images. Automatic CT image co-registration was followed by
      manual co-registration taking into account the CTV-PROS contour and soft tissue
      informations. Deviations of the isocentres in lateral (LAT), longitudinal (LONG)
      and vertical (VERT) directions were recorded after each image co-registration.
      Corresponding data were compared using the t-probe. Systematic (S) and random (s)
      errors of the set up were calculated. Adequate PTV to CTV margins were calculated
      by van Herk's formula (2.5xS + 0,7xs). Overall 252 deviations were analysed on
      fourty-two CT series of 10 patients. The mean errors of the set up with automatic
      and manual image co-registrations were 0.19 cm and 0.07 cm (p=0.001) in LAT, 0.05
      cm and 0.03 cm (p=0.07) in LONG and 0.16 cm and 0.22 cm (p=0.16) in VERT
      directions, respectively. The systematic errors of the set up for automatic and
      manual image registrations were 0.22 cm and 0.26 cm in LAT, 0.17 cm and 0.18 cm
      in LONG, 0.25 cm and 0.26 cm in VERT directions, respectively. The random errors
      of the set up for automatic and manual image registrations were 0.31 cm and 0.26
      cm in LAT, 0.27 cm and 0.27 cm in LONG and 0.24 cm and 0.33 cm in VERT
      directions, respectively. In case of manual image co-registration, the required
      PTV to CTV margins to cover at least 95% of the CTVs with at least 95% percent of
      the prescribed dose were calculated to 0.93 cm in LAT, 0.65 cm in LONG, and 0.89
      cm in VERT directions. Patients set up can be verified with manual image co
      registration based on soft tissues around the prostate using a kV CT-on-rails
      system installed in the treatment room. The difference between automatic and
      manual image co-registration was significant in LAT direction. A PTV to CTV
      margin <1 cm seems to be appropriate to cover the CTVs in image-guided prostate
      radiotherapy. These findings support our recent clinical protocol.

PMID- 23008830
TI  - The evaluation of Coulombic interaction in the oriented-attachment growth of
      colloidal nanorods.
AB  - An analytical expression of Coulomb interaction between a sphere and a
      cylindrical rod was derived. Along with a recently reported van der Waals
      interaction expression, the derived Coulomb interaction expression, for the first
      time, allows one to quantitatively evaluate the activation energy in the oriented
      attachment growth of colloidal nanorods.

PMID- 23008831
TI  - A new strategy for effective construction of protein stacks by using
      cucurbit[8]uril as a glue molecule.
AB  - Cucurbit[8]uril (CB[8]) is found to induce the aggregation of pristine proteins
      in aqueous solution. Based on this finding, a new strategy for effective
      construction of layer-by-layer homo- and hetero-protein stacks was developed,
      where their bioactivities are preserved.

PMID- 23008829
TI  - [Nintedanib (BIBF 1120) in the treatment of solid cancers: an overview of
      biological and clinical aspects].
AB  - Angiogenesis is essential for tumor growth and metastasis. The main regulators of
      the process are the signaling cascades of VEGF-, PDGF- and FGF receptors.
      Inhibition of these pathways holds potential therapeutic benefit not only for
      cancer patients, but also for the treatment of other diseases. This paper
      summarizes the experimental and clinical results of studies available so far on
      the multi-target tyrosine kinase inhibitor nintedanib (BIBF 1120). According to
      these studies, nintedanib effectively inhibits VEGFR-, PDGFR- and FGFR
      signalization and thus the proliferation and survival of cell types which highly
      express these receptors (i.e. endothelial and smooth muscle cells and pericytes).
      In vitro studies and in vivo xenograft experiments have provided promising
      results. In the clinical setting, BIBF 1120 seems to be effective and well
      tolerated in various tumor types, such as lung, prostate, colorectal and
      hepatocellular carcinoma, as well as in gynecological tumors. The main adverse
      events are gastrointestinal toxicities and the reversible elevation of liver
      enzyme levels. Nintedanib might also be combined with paclitaxel, carboplatin,
      pemetrexed and docetaxel. There are several ongoing clinical trials testing the
      efficacy of BIBF 1120.

PMID- 23008832
TI  - Facile one-pot preparation of calcite mesoporous carrier for sustained and
      targeted drug release for cancer cells.
AB  - Herein, mesoporous calcite/chondroitin sulfate hybrid microrods are prepared
      through a one-pot method. Biological assays indicate that the microrods might be
      used as good active targeted drug delivery carriers to treat tumor tissues with
      high specificity and low toxic side effects.

PMID- 23008833
TI  - Molecular interactions of 2'-deoxyguanosine 5'-monophosphate with glycine in
      aqueous media probed via concentration and pH dependent Raman spectroscopic
      investigations and DFT study.
AB  - In order to gain insights into nucleotide-protein interaction, the molecular
      interaction of glycine (Gly) with 2'-deoxyguanosine 5'-monophosphate (dGMP) was
      monitored in aqueous media through Raman spectroscopic measurements and density
      functional theory (DFT) calculations. Raman spectra of dGMP, glycine and their
      binary mixtures (dGMP + Gly) in aqueous media at 10 different concentrations
      corresponding to the dGMP : Gly molar ratios varying from 1 : 1 to 1 : 10 were
      recorded in the fingerprint region 2000-400 cm(-1). Raman spectra of the dGMP :
      Gly mixture with a molar ratio of 1 : 3 in aqueous media at 10 different pH
      values starting from 1 to 10 at an interval of 1 were also recorded. The DFT
      calculations were performed on dGMP, glycine and their various complexes with
      varying number of H(2)O molecules in gas phase as well as in solvation using
      hybrid functional B3LYP employing the high level basis set 6-311+G(d,p). The
      variations in the observed spectral features were explained in terms of
      calculated optimized structures of dGMP, glycine and their various complexes with
      water molecules and a good spectra-structure correlation was obtained. Raman
      spectra of glycine in 1.2 M aqueous solution were also recorded at three pH
      values, 2, 6 and 10, and the subtle differences in the spectral features were
      correlated with the calculated Raman spectra of protonated, deprotonated and
      zwitterionic forms of glycine. The results also give experimental evidence rather
      convincingly that the zwitterionic and protonated forms of glycine are formed at
      pH = 6 and 2, respectively, but even at pH = 10, deprotonated glycine is not
      formed. An important aspect of this study is the monitoring of the interaction of
      dGMP with the zwitterionic form of glycine giving insightful details regarding
      the binding site.

PMID- 23008834
TI  - Novel group 13 Lewis superacids and 13-15 donor-acceptor cryptands for hydrogen
      activation: a theoretical study.
AB  - Structures of group 13 Lewis acids ER(3) and group 15 Lewis bases YR'(3) as well
      as respective hydrogen splitting products [HER(3)](-) and [HYR'(3)](+) (E = B,
      Al, Ga; Y = N, P, As; R(3) = (C(6)F(5))(3), (C(6)H(2)F(2))(3)CF; R' = H,
      C(6)H(5), 2,6-Me(2)C(6)H(3)) have been fully optimized at B3LYP/pVDZ and
      B3LYP/def2-TZVPP levels of theory. Energetic characteristics of the hydrogen
      splitting process ER(3) + YR'(3) + H(2) = [HYR'(3)](+) + [HER(3)](-) have been
      obtained. Energetics for the ion formation does not depend on the nature of group
      13 element E. However, the Lewis acid environment (pyramidal vs. planar) and
      nature of Lewis base play a significant role in the energetics of heterocyclic
      hydrogen splitting. The endothermicity of the heterolytic hydrogen splitting
      process is reduced by about 80 kJ mol(-1) by using pyramidal Lewis acids
      E(C(6)H(2)F(2))(3)CF, and by 40 kJ mol(-1) by using Lewis bases with 2,6
      Me(2)C(6)H(3) substituents. Thus, the overall process of the heterolytic hydrogen
      splitting is predicted to be endothermic by only 130 kJ mol(-1) for the
      E(C(6)H(2)F(2))(3)CF-P(2,6-Me(2)C(6)H(3))(3) combinations (compared to 450 kJ
      mol(-1) for E(C(6)F(5))(3)-PH(3)). It is shown that H(2) splitting in the gas
      phase by nitrogen-containing DA cryptands, featuring group 13 element acceptor
      centers with a pyramidalized environment, is highly exothermic.

PMID- 23008835
TI  - Kinetic study of the reaction of vanadium and vanadium-titanium oxide cluster
      anions with SO2.
AB  - The reactivity of mass-selected V(4)O(10)(-) cluster anions towards sulphur
      dioxide is investigated in an ion trap under multi-collision conditions. Gas
      phase reaction kinetics are studied as a function of temperature (T(R) = 150-275
      K). The binding energy of SO(2) to V(4)O(10)(-) is obtained by analyzing the
      experimental low pressure rate constants, employing the Lindemann energy transfer
      model for association reactions in conjunction with statistical RRKM theory. In
      addition, infrared multiple photon dissociation spectroscopy is used in
      conjunction with density functional theory for the structural assignment of the
      [V(4)O(10)(-), SO(2)] complex, revealing a square pyramidal structure with the
      SO(2) molecule incorporated in the vanadium oxide framework. Energy profiles are
      calculated for the reaction between V(4)O(10)(-) and V(6)O(15)(-) with SO(2).
      Whereas the transition structures along the reaction pathway of V(4)O(10)(-) with
      SO(2) have energies below those of the separated partners, the reaction of
      V(6)O(15)(-) with SO(2) proceeds via a transition structure with energy higher
      than the educts. The role of cluster size and composition is investigated by
      studying the reaction kinetics of larger (V(6)O(15)(-) and V(8)O(20)(-)) and
      titanium doped (V(3)TiO(10)(-) and V(2)Ti(2)O(10)(-)) vanadium oxide clusters
      with SO(2). The observed cluster size and composition dependencies are discussed.

PMID- 23008836
TI  - Translational research at the interface of neurology and psychiatry. Abstracts of
      the 2012 AFPBN (French Association for Psychiatric Biology and
      Neuropsychopharmacology) Annual Meeting. March 15-17, 2012. Paris, France.

PMID- 23008837
TI  - Exempting in-home video telehealth from copayments. Direct final rule;
      confirmation of effective date.
AB  - The Department of Veterans Affairs (VA) published a direct final rule amending
      its regulation that governs VA services that are not subject to copayment
      requirements for inpatient hospital care or outpatient medical care.
      Specifically, the regulation exempted in-home video telehealth care from having
      any required copayment. VA received no significant adverse comments concerning
      this rule or its companion substantially identical proposed rule published on the
      same date. This document confirms that the direct final rule became effective on
      May 7, 2012. In a companion document in this issue of the Federal Register, we
      are withdrawing as unnecessary the proposed rule.

PMID- 23008838
TI  - Women in engineering.

PMID- 23008839
TI  - Graduate school: the problem of choice.

PMID- 23008840
TI  - Southern California: a hotbed of biomedical engineering: nine bioengineers
      describe their research and why Southern California has the biotech market
      cornered.

PMID- 23008842
TI  - Tomato genome gets fully decoded--paves way to tastier and healthier fruits.

PMID- 23008843
TI  - Inspiring engineering minds to advance human health: the Henry Samueli School of
      Engineering's Department of BME.
AB  - The growth of biomedical engineering at The Henry Samueli School of Engineering
      at the University of California, Irvine (UCI) has been rapid since the Center for
      Biomedical Engineering was first formed in 1998 [and was later renamed as the
      Department of Biomedical Engineering (BME) in 2002]. Our current mission
      statement, "Inspiring Engineering Minds to Advance Human Health," serves as a
      reminder of why we exist, what we do, and the core principles that we value and
      by which we abide. BME exists to advance the state of human health via
      engineering innovation and practices. To attain our goal, we are empowering our
      faculty to inspire and mobilize our students to address health problems. We
      treasure the human being, particularly the human mind and health. We believe that
      BME is where minds are nurtured, challenged, and disciplined, and it is also
      where the health of the human is held as a core mission value that deserves our
      utmost priority (Figure 1). Advancing human health is not a theoretical practice;
      it requires bridging between disciplines (engineering and medicine) and between
      communities (academic and industry).

PMID- 23008844
TI  - Optimised design and development of a bio-medical healthcare device through
      quality function deployment (QFD).
AB  - Technology is major stimulus for change and is imbibed in various forms;
      especially in the field of medical devices and bio-medical instruments used in
      life and death situations. Cardiotocograph (CTG), a foetal heart rate and uterine
      contraction monitoring and measurement machine, is a valuable tool in the process
      of childbirth. The Quality Function Deployment (QFD) is an engineering technique
      with the number one priority being to satisfy the customer. The aim of using QFD
      in this paper is to highlight the limitations and complexities of the present
      instrument. The paper attempts to first discuss out the operational details of
      the instrument along with a brief review of the relevant literature. Following
      this, its functional analysis is carried out through QFD - a TQM tool. The
      resultant outcome enlists CTG functions with their Raw Weight and Priority Score.
      A detailed theoretical analysis of results pinpoints basic functional limitation
      of exiting machine.

PMID- 23008845
TI  - Production of large unilamellar vesicles by a rapid extrusion procedure:
      characterization of size distribution, trapped volume and ability to maintain a
      membrane potential.
AB  - A technique for the rapid production of large unilamellar vesicles by repeated
      extrusion under moderate pressures (<= 500 lb/in2) of multilamellar vesicles
      through polycarbonate filters (100 nm pore size) is demonstrated. In combination
      with freeze-thaw protocols where required, this procedure results in unilamellar
      vesicles with diameters in the range 60-100 nm and with trapped volumes in the
      region of 1-3 MUl/MUmol phospholipid. Advantages of this technique include the
      absence of organic solvents or detergents, the high lipid concentrations (up to
      300 MUmol/ml) that can be employed and the high trapping efficiencies (up to 30%)
      that can be achieved. Further, the procedure for generating these 'LUVET's'
      (large unilamellar vesicles by extrusion techniques) is rapid (<= min preparation
      time) and can be employed to generate large unilamellar vesicles from a wide
      variety of lipid species and mixtures. As a particular illustration of the
      utility of this vesicle preparation, LUVET systems exhibiting a membrane
      potential (DeltaPsi) in response to a transmembrane Na+/K+ gradient (K+ inside)
      have been characterized. By employing the lipophilic cation
      methyltriphenylphosphonium (MTPP+) it is shown that a K+ of diffusion potential
      (DeltaPsi < -100 mV) forms rapidly in the presence of the K+ ionophore
      valinomycin for soya phosphatidylcholine (soya PC) LUVET's. The values of
      Deltapsi obtained correlate well with the K+ concentration gradient across the
      membrane, and it is demonstrated that the decay of Deltapsi with time depends on
      the flux of Na+ into the vesicles.

PMID- 23008846
TI  - [Post-infectious irritable bowel syndrome in the community: a prospective cohort
      study].

PMID- 23008847
TI  - [Low vaccine coverage in indigenous migrant boys and girls].

PMID- 23008848
TI  - [Prevalence of bullying among students at a public secondary school].

PMID- 23008849
TI  - [Suicide among South American adolescents: a growing problem].

PMID- 23008850
TI  - [H1N1 influenza A in pediatric patients in a university hospital].

PMID- 23008851
TI  - [Actinomycosis in pancreas and psoas muscle].

PMID- 23008852
TI  - [Practice guideline for the diagnosis and management of non-alcoholic fatty liver
      disease].

PMID- 23008853
TI  - [Verification of sterilization cycles at dental practices in San Luis Potosi,
      Mexico].

PMID- 23008854
TI  - Should veterinary technicians be allowed to perform dental extractions?

PMID- 23008855
TI  - Comparing the degree of exothermic polymerization in commonly used acrylic and
      provisional composite resins for intraoral appliances.
AB  - The use of dental acrylics and composite resins in veterinary dentistry has
      become widespread. However their use is not without potential complications. All
      acrylics and composite resins produce an exothermic reaction during the
      polymerization process. The aim of the current study was to evaluate thermal
      conduction during the polymerization reaction of each material to offer clinical
      guidelines when choosing a material with particular consideration for the
      significant volumes typically used. Results showed that methylmethacrylate based
      resins generated a significantly higher degree of heat during polymerization. Bis
      acryl based composite resins generated a significantly lower degree of heat
      during polymerization, making them the material of choice to potentially minimize
      thermal injury to the dentin-pulp complex. It is the responsibility of the
      clinician to become aware of all materials available, and to have an
      understanding of their properties to guide them in making sound clinical
      judgments.

PMID- 23008856
TI  - Retention of antimicrobial activity after reconstitution of doxycycline gel.
AB  - Doxycycline gel is licensed for the treatment of periodontal disease in dogs.
      Package labeling indicates the product is stable after reconstitution of
      antibiotic with polymer gel for up to 3-days when stored at room temperature. The
      purpose of this study was to determine if reconstituted doxycycline gel retained
      antimicrobial activity for greater than 3-days. The antibiotic activity of
      reconstituted doxycycline gel was evaluated against antimicrobial testing strains
      of bacteria and bacteria collected from throat swabs of 2 dogs using a standard
      disc diffusion assay. Our results showed that reconstituted doxycycline gel
      retained undiminished antimicrobial activity for a minimum of 8-weeks.

PMID- 23008858
TI  - Multicentric oral plasmacytoma in 3 dogs.
AB  - Oral extramedullary plasmacytomas (EMP) are locally aggressive tumors in the dog
      that rarely metastasize. They represent 5.2% of all canine oral tumors and 22.0
      to 28.0% of all EMPs diagnosed are in the oral cavity. EMPs consist of neoplastic
      plasma cells that do not arise from the bone marrow. No relationship between EMP
      and the development of multiple myeloma has been determined in dogs. Complete
      surgical excision is the primary treatment for this neoplasm and is usually
      curative. Multiple oral EMPs within the same patient have been rarely reported
      with tumors arising in the same location in the mouth. To the authors' knowledge,
      multicentric oral EMP, as described in the following cases, has not been reported
      in the dog.

PMID- 23008857
TI  - Efficacy of a barrier gel for reducing the development of plaque, calculus, and
      gingivitis in cats.
AB  - This study was performed to assess the field efficacy of a professional and home
      care barrier gel against the development of plaque, calculus, gingival bleeding,
      and gingivitis in client-owned cats over a 56-day period compared with negative
      controls. In a randomized, negative-controlled, outcome evaluator-blinded, client
      owned animal clinical field study, 31 cats were evaluated to assess if the
      barrier gel dental product was effective in cats. Following an enrollment
      qualification assessment and enrollment of each cat, all cats received a
      professional dental cleaning, including polishing and irrigation. Following
      cleaning, a post-cleaning assessment was performed by the evaluator. Then, using
      a pre-developed randomization schedule, cats were assigned to the treated or
      control group. The professional version of the barrier gel was applied to the
      treated group on day 0. The negative-control group patients did not receive any
      applications of the barrier gel following dental cleaning. Treated-group cats
      were brought back to the clinic for subsequent applications of the home-care
      version of the barrier gel, applied by a non-blinded trained assistant. The home
      care version product applications began on day 14 and then were applied weekly
      (days, 21, 28, 35, 42, 49 and 56) through day 56. All cats enrolled in the study
      underwent full oral examinations and assessments by the blinded evaluator on or
      about their respective days 28 and 56. At these evaluations, the evaluator
      performed standardized assessments for plaque, calculus, gingivitis, and gingival
      bleeding. Numeric scores were assigned for each assessment using predetermined
      target teeth to ensure consistency. Using these assessment scores, statistical
      analyses were performed to determine the efficacies against plaque and calculus
      deposition; additionally, measurements of gingivitis and gingival bleeding were
      assessed. Change in plaque score from baseline, for all teeth assessed (all 4
      canine teeth, and all 4 [corrected] premolar teeth), was significantly (P < 0.05)
      lower for treated cats than for control cats for both left side average and right
      side average on day 56. No statistical differences were seen for calculus,
      gingivitis, or gingival bleeding in this study. In cats with a history of
      developing plaque, application of the barrier gel dental product following dental
      cleaning reduced plaque deposition (P < 0.05) compared with control cats.

PMID- 23008859
TI  - Developmental tooth anomaly in a cat.

PMID- 23008860
TI  - Periodontal hand instruments.

PMID- 23008861
TI  - Surgical extraction of the mandibular canine tooth in the cat.

PMID- 23008862
TI  - What's new?

PMID- 23008863
TI  - Managing minor wounds.

PMID- 23008864
TI  - Liability for student deaths from asthma.

PMID- 23008865
TI  - How school nurses are implementing the 2010 National Diabetes Education Program's
      School Guide.

PMID- 23008866
TI  - Do I really need to buy the newest edition of School Nursing: a comprehensive
      text?

PMID- 23008867
TI  - Symptoms and treatment of anxiety disorders.

PMID- 23008868
TI  - Understanding the different methods for taking a temperature.

PMID- 23008869
TI  - Implementing pulse oximetry in the school health office: the time is now.
AB  - Pulse oximetry can be a useful tool for professional school nurses who daily
      assess students with a variety of health issues and injuries. Pulse oximeters are
      now smaller and more affordable and, therefore, an option for school districts to
      purchase. Before implementing this new tool into their practice, school nurses
      must have an understanding of how pulse oximeters work and how they measure the
      oxygen saturation of arterial hemoglobin. A review of the literature will guide a
      nurse in developing clinical guidelines for practice and facilitating competency
      in using a pulse oximeter with the ultimate goal of improving student health
      assessments.

PMID- 23008870
TI  - Creating a new community of support for students with food allergies.
AB  - Managing food allergies in schools is a necessary but complex task. Breakdowns in
      implementation of school policies have resulted in devastating consequences and
      can create a divided school community. School nurses play the central role in the
      food allergy education of staff parents and students. An educated school
      community can then be united in supporting children with food allergies. A
      thoughtful approach that takes these different members of the school community
      into consideration is essential to put a successful food allergy policy into
      action. This article outlines issues to consider when educating each specific
      group as well as discussing the challenges that can hamper school community-wide
      education and their potential solutions. The ultimate goal of food allergy
      management education is to create a community of support and to create a self
      sustaining environment of understanding and awareness that may save time,
      decrease divisiveness, and even save a life.

PMID- 23008871
TI  - Bed bugs: they are back! The role of the school nurse in bed bug management.
AB  - Recently there has been a resurgence of bed bugs in all facets of our society.
      Bed bugs have even been found in schools, causing unnecessary exclusion of
      students and unfounded hysteria. School nurses are again called upon to be front
      line sources of information to quell the hysteria and confusion related to this
      unsavory condition. By arming themselves with the best evidence regarding proper
      identification of bed bugs and their bites and information about integrated
      prevention measures to control transmission of infestations, school nurses can
      contribute to the control and management of bed bugs and aid in the overall
      battle against this "new and improved" invasion of the bed bugs.

PMID- 23008872
TI  - Danger zone.

PMID- 23008873
TI  - The allergic march.

PMID- 23008874
TI  - A topic in 10 questions: how to manage reflux in infants.

PMID- 23008875
TI  - A bright start.

PMID- 23008876
TI  - The power of play.

PMID- 23008877
TI  - Going for gold.

PMID- 23008878
TI  - Mothers and babies--reducing risk through audits and confidential enquiries.

PMID- 23008879
TI  - Quality measures in breast cancer surgery.

PMID- 23008880
TI  - Atrial fibrillation--not so NICE in Ireland!

PMID- 23008881
TI  - Suicide in children over two decades: 1993-2008.
AB  - Suicide rates have increased in Ireland's youth over the past two decades.
      However, no research report has focussed on suicide rates in those aged under 18-
      the children of Ireland. We retrieved national disaggregated age and sex-specific
      suicide mortality data from 1993-1998 and compared it with similar suicide
      mortality data from 2003-2008. Significant age (older vs younger) and sex effects
      (boys greater risk than girls) are apparent in both decades Suicide rates in both
      males and females have increased (males: 9.3-13.5/100,000), (females: 2.4
      5.1/100,000. Suicide rates in under 15 year olds boys and girls is extremely rare
      for both time periods studied (1.6/100,000). Results are discussed in light of
      the rights of children and the obligation of the nation in this regard, as well
      as more child-specific and transition to adulthood-specific suicide prevention
      policy implications.

PMID- 23008883
TI  - Periconceptional folic acid supplementation in a nationally representative sample
      of mothers.
AB  - This study reports recent trends in periconceptional folic acid use in Ireland
      using archived data from Growing Up in Ireland--the National Longitudinal Study
      of Children. Of a sample of 10,891 mothers, 6,936 (64%) reported taking folic
      acid before conception and 10,157 (93%) reported taking folic acid during the
      first trimester of pregnancy. Younger (OR = 0.38, 95% CI = 0.29-0.50), lower
      income (OR = 0.59, 95% CI = 0.51-0.68), lower educated (OR = 0.77, 95% CI = 0.66
      0.89), and single mothers (OR = 0.46, 95% Cl = 0.40-0.52) were less likely to
      have taken folic acid pre-conception. A similar pattern was found post-conception
      with younger (OR = 0.58, 95% Cl = 0.40-0.84), lower income (OR = 0.40, 95% Cl =
      0.30-0.53), lower educated (OR = 0.50, 95% Cl = 0.38-0.66), and single mothers
      (OR = 0.74, 95% CI = 0.60-0.91) less likely to have taken folic acid post
      conception. The findings highlight an ongoing need for targeted promotional
      campaigns to increase supplementation rates among younger and socially
      disadvantaged mothers.

PMID- 23008882
TI  - Improving patient care--the first year in a dedicated surgical assessment unit.
AB  - A surgical assessment unit (SAU) was established in October 2009 at the Mid
      Western Regional Hospital. We assessed this servic in its initial year and
      compared it to Emergency Department (ED) services. We audited SAU and ED
      databases and theatre logbooks from November 2009 to October 2010. 1949 patients
      were referred to the SAU and 857 patients were admitted (44%). Only 44 SAU
      patients (6%) waited more than 6 hours for a bed compared to 828 patients (68%)
      admitted through the ED. SAU patients who required emergency surgery had a
      shorter waiting time before theatre (37 (18.6%) vs 9(6%) waited less than 6
      hours, p < 0.05). To summarise, we found that almost 2,000 patients who would
      otherwise have presented to the ED were referred to the SAU. Waiting times for
      admission and theatre were significantly shorter. Further resource allocation
      could expand the service and improve it further, by diverting more patients from
      the ED.

PMID- 23008884
TI  - "In somno securitas" anaesthetists' noise exposure in Orthopaedic operating
      theatres.
AB  - Excessive noise exposure can have adverse effects on the health and performance
      of healthcare providers. Irish statutory regulations limit daily workplace noise
      exposure to 87 A-weighted decibels [dB(A)]. The World Health Organisation
      recommends noise levels remain under 35 dB(A) in patient treatment rooms. We
      measured anaesthetists' noise exposure during elective orthopaedic surgery. The
      mean and maximum sound levels were 63.0 (SD 4.26) and 92.8 dB(A) respectively.
      Noise was louder than 65 dB(A) 22.2% of the time and louder than 80 dB(A) less
      than 1% of the time. Staff conversation and metal instruments were responsible
      for 29.5% and 19.9% of peaks louder than 65 dB(A) respectively. Sound levels
      recorded were lower than recognised levels associated with hearing loss. Sound
      regularly exceeded World Health Organisation (WHO) recommended levels for patient
      comfort and safety. Anaesthetists need to be aware of the influence of
      environmental noise on clinical practice.

PMID- 23008885
TI  - Transanal irrigation in the management of neurogenic bowel dysfunction.
AB  - Many patients with a spinal cord injury (SCI) or spina bifida suffer from
      neurogenic bowel dysfunction which causes significant physical and psychological
      morbidity. For the last four years at the National Rehabilitation Hospital,
      transanal irrigation (TAI) has been offered to patients who were dissatisfied
      with a conservative bowel management programme. This is an observational study of
      eleven patients who were offered TAI. Three questionnaires, scoring bowel
      symptoms at baseline and follow-up (3-28 months) were completed by patients. Nine
      patients had a SCl and two had spina bifida, mean age was 44 years. A reduction
      in mean scores for all three questionnaires occurred post TAI (39.5-42.1%)
      indicating fewer bowel symptoms. Statistically significant reductions in faecal
      incontinence (p < 0.05), abdominal pain (p < 0.05) and lifestyle alterations
      secondary to bowel management (p < 0.05) occurred. No serious adverse events
      occurred during the study. TAI is an effective treatment option for the
      management of neurogenic bowel dysfunction.

PMID- 23008886
TI  - The case for cognitive screening in HIV clinics.
AB  - A retrospective chart review was carried out at the HIV clinic in St. James's
      Hospital, Dublin to examine the rate of cognitive impairment through the use of
      surrogate markers for cognitive impairment. 500 consecutive hospital charts were
      reviewed. There were 306 men and 194 women. Median age was 37. The most common
      mode of transmission was heterosexual. 45% had a nadir CD4 < 200. 78.6% were on
      antiretroviral therapy and 72.26% were virally suppressed. 69/500 patients
      (13.8%) had one or more positive surrogate markers for cognitive impairment. The
      surrogate markers used were subjective complaints, a new onset of a psychiatric
      diagnosis post diagnosis with HIV, neurological complications and radiological
      evidence of atrophy. Multivariate analysis using logistic regression showed
      significant relationships only with gender and year of diagnosis. This figure is
      lower than reported international prevalence rates of cognitive impairment and
      demonstrates that surrogate markers are no match for structured cognitive
      screening. We have since commenced structured prospective screening to obtain a
      true prevalence of cognitive impairment in this population.

PMID- 23008887
TI  - Blowout fracture of the orbital floor secondary to vigorous nose blowing.
AB  - Orbital floor fracture due to vigorous nose blowing in the absence of mechanical
      trauma is rare, only four cases having previously been reported. In each of these
      cases, predisposing factors have been identified; preceding URTI in three and a
      history of sino-nasal surgery in the fourth case. We present the case of a 49
      year-old woman who developed a maxillary sinus fracture and orbital emphysema
      after blowing her nose.

PMID- 23008888
TI  - Pancreatico pleural fistula: an unusual complication of chronic pancreatitis.
AB  - Pancreatico-pleural fistula secondary to chronic pancreatitis is a rare cause of
      pleural effusion. This case report presents a case of a middle aged female, a
      known case of chronic pancreatitis who presented with severe epigastric pain and
      progressive shortness of breath. CT and MRCP were useful in visualising the
      fistulous communication between the pancreas and pleural cavity. Treatment
      consisted of ERCP placement of a pancreatic stent, which facilitated internal
      drainage of pancreatic fluid thus resolving the pleural effusion and promoting
      healing of the fistula.

PMID- 23008889
TI  - The non specialist paediatric training registrar in the healthcare system.
AB  - This study evaluated the experiences of non Specialist Paediatric Training
      Registrars (nonSPTR) in the Irish Healthcare system. The survey explored their
      adaptation to the healthcare system, skill development, perceptions of training
      and career development inclusive of working conditions. Thirty nine (53%) doctors
      responded. The time spent in Paediatrics ranged from 3 to 19 years with a mean of
      8.9 years. Nineteen (49%) had only worked in non regional hospitals and for 20
      (51%) the mean time spent in regional hospitals was 2.6 years. The very positives
      experiences (likert scores 5/6) included journal appraisal for 19 (49%), clinical
      skill development for 17 (44%) and consultant feedback for 11 (28%).The very
      negative experiences were difficulty obtaining desired clinical posts for 16
      (43%) doctors and only 5 (13%) were happy with their career progression. Thirty
      one (79.5%) cited specific barriers to career progression, with only 10 (25%)
      making an application to the Specialist Paediatrics Registrar (SPR) training
      programme. Solutions for the non SPTR difficulties include the expansion of the
      SPR programme and the utilization of a criterion based portfolio system to
      integrate the nonSPTR into formal training.

PMID- 23008890
TI  - Regionalisation and neonatal networks.

PMID- 23008891
TI  - Appropriateness of bleeps: an audit of the bleep system over two week period.

PMID- 23008892
TI  - Thrombophilia testing--reducing the burden.

PMID- 23008894
TI  - Make staffing levels mandatory.

PMID- 23008893
TI  - The HSE/ICGP guidelines on the management of depression and anxiety disorders in
      primary care.

PMID- 23008895
TI  - Safety compromised by rising workloads.

PMID- 23008896
TI  - Experience is best foundation for careers in leadership.

PMID- 23008897
TI  - Expert group devises tool to evaluate learning disabilities care outcomes.

PMID- 23008898
TI  - Warning system prompts staff to step up care.

PMID- 23008899
TI  - Patients deserve a say.

PMID- 23008900
TI  - What influences mentors to pass or fail students.
AB  - The aim of the study was to establish mentorship practice in relation to the
      University of the West of Scotland pre-registration nursing students. Surveys
      were sent to 4,341 mentors, with a 41 per cent response rate. Results show that
      18 per cent of participants had passed a failing student. A number of factors
      influenced mentors' decisions, which to some extent echo findings from previous
      research. However, this study provides new perspectives on failing to fail and
      considers the supportive role of universities in relation to mentors and
      students' practice placements. The knowledge derived from this study will help
      inform mentoring and mentorship practice to ensure only safe and competent
      practitioners gain entry to the register.

PMID- 23008901
TI  - How nurse leaders can foster a climate of good governance.
AB  - This article is the first in a series of four examining the components of good
      corporate governance. Poor governance can result in patients receiving poor
      quality care; all healthcare professionals, therefore, have a role in ensuring
      effective governance. This article discusses how an organisation's culture and
      leadership can contribute to good corporate governance. Nurse leaders can
      influence the culture of effective governance by building trust and respect and
      challenging the behaviours that led to poor quality care. The next article in
      this series will look at how an organisation's systems and processes can affect
      the effectiveness of its governance.

PMID- 23008902
TI  - Developing an e-learning resource in clinical risk assessment.
AB  - This article describes a project in which computer-centred technology was used to
      deliver clinical risk assessment training to staff in a specialist addictions
      unit. The difficulty in releasing staff from already stretched services led to
      the development of an in-house e-learning tool designed to bridge the gap between
      standardised risk assessment training and the requirements of staff who work in
      addictions services. The e-learning tool was developed on a small budget and is
      fairly rudimentary, but has been well received by staff, although they do not
      regard it as a replacement for classroom-based teaching. This was a pilot project
      that aimed to develop the resource and consider its use as a method of future
      training delivery.

PMID- 23008903
TI  - Partnering industry to develop clinical information systems.
AB  - Over the past six months, the nursing team from the Department of Health's
      Informatics Directorate has been working with colleagues in industry to promote
      and share learning and understanding of issues surrounding the nursing
      profession. Team members were asked among other things to identify key questions
      senior nursing colleagues and suppliers should ask one another when considering
      the implementation of a new system for recording clinical information and
      extracting pertinent data. This article aims to encourage collaborative working
      and understanding of the importance of senior nurse involvement in choosing and
      delivering the right system for staff and patients.

PMID- 23008904
TI  - Advancing patient care.

PMID- 23008905
TI  - Learning about other countries and cultures shouldn't stop with the Olympics.

PMID- 23008906
TI  - Oncology nursing, international style: sharing information and best practices
      across cultures and customs.

PMID- 23008907
TI  - How has ONS helped you to perform cancer care internationally?

PMID- 23008908
TI  - Manage side effects of cabazitaxel in patients with castrate-resistant prostate
      cancer.

PMID- 23008909
TI  - FDA remodels REMS for opioid medications.

PMID- 23008910
TI  - The case of the catabolic catastrophe.

PMID- 23008911
TI  - Some children with Hodgkin lymphoma may not require radiation therapy.

PMID- 23008912
TI  - Standards aim to boost care.

PMID- 23008913
TI  - Government's lack of clarity on funding could affect services.

PMID- 23008914
TI  - Deprivation of liberty safeguard.

PMID- 23008915
TI  - An overview of foot ulceration in older people with diabetes.
AB  - A patient's whole body is affected by diabetes but in particular this chronic
      disease can cause foot complications. Damage to the nerve and blood supply to the
      feet as a result of diabetes causes lack of sensation and ischaemia. These
      problems can lead to diabetic foot ulceration, which, if left untreated, can
      result in amputation or even death. An essential part of nurses' role in caring
      for older patients with diabetes in community, acute and residential settings is
      learning to recognise the signs of a high-risk diabetic foot, and when and where
      to get help for its treatment.

PMID- 23008916
TI  - The role of telemonitoring in caring for older people with long-term conditions.
AB  - Long-term conditions have a negative effect on the lives of older people and
      those who care for them. As the population ages, so the prevalence of long-term
      conditions increases, which presents substantial challenges to providers of
      health and social care. This article examines how telemonitoring could help to
      meet some of these challenges. Telemonitoring involves patients at home recording
      vital signs, for example, blood pressure and pulse, and transmitting this
      information electronically to nurses based elsewhere. Nurses can then use these
      data to identify signs of deterioration, intervene promptly and prevent admission
      to hospital. There is some evidence that this form of care is popular with
      patients and can improve clinical outcomes. However, nurses should ensure that
      they understand the opportunities and difficulties presented by telemonitoring,
      develop the skills necessary to use it effectively and put themselves at the
      forefront of this innovative method of supporting care provision.

PMID- 23008917
TI  - Safeguarding older patients.
AB  - Active involvement of patients, relatives and staff in the clinical processes of
      assessment, care planning, evaluation of care and audit of clinical practices can
      improve standards of care to patients and encourage an open culture in which
      concerns are raised and resolved promptly. Through good safeguarding practice,
      hospital teams can ensure that processes and systems of care are appropriate for
      individuals and do not subject patients to harm. For staff to feel confident in
      reporting safeguarding incidents and raising patients' or relatives' concerns,
      they need to have confidence in the leadership and processes of safeguarding in
      their organisation. Safeguarding should focus on developing and improving
      standards of care, become embedded into the culture of the organisation, be seen
      as integral to the management and organisation of care and supported and promoted
      through clinical leadership.

PMID- 23008918
TI  - Managing agitated behaviour in older people.
AB  - Older people diagnosed with dementia can have complex needs, especially when they
      exhibit agitated behaviour. Patients with agitated behaviour challenge the
      delivery of health care. Often the behaviour is a symptom of unmet needs in this
      population (Dewing 2010). It is important for nurses to understand the underlying
      causes and apply evidence-based interventions in their nursing practice to
      promote health, safety and the highest quality of life possible. This article
      defines and classifies agitated behaviours, discusses implications for their
      management and then presents evidence-based interventions nurses can use. The
      interventions are categorised according to each of the five senses.

PMID- 23008919
TI  - Seize each opportunity.

PMID- 23008920
TI  - Estimating prevalence of chronic obstructive pulmonary disease: from
      questionnaires to spirometry.

PMID- 23008921
TI  - Drug-resistant tuberculosis: new challenges.

PMID- 23008922
TI  - Treatment practices in pulmonary tuberculosis by private sector physicians of
      Meerut, Uttar Pradesh.
AB  - BACKGROUND: Majority of the qualified medical practitioners in the country are in
      the private sector and more than half of patients with tuberculosis (TB) seek
      treatment from them. The present study was conducted with the objective of
      assessing the treatment modalities in pulmonary tuberculosis by the private
      physicians in Meerut City, Uttar Pradesh, India. METHODS: A cross-sectional study
      was carried out covering all the private physicians (graduates and postgraduates
      in Medicine and Chest Diseases) registered under the Indian Medical Association,
      Meerut Branch (n = 154). The physicians were interviewed by a pre-designed and
      pre-tested questionnaire about the treatment modalities practiced by them.
      RESULTS: Only 43.5% private physicians had attended any Revised National
      Tuberculosis Control Programme (RNTCP) training in the past five years. Only
      33.1% of them were aware of the International Standards of Tuberculosis Care
      (ISTC). Fifty-three different regimens were used to treat the patients. Majority
      of physicians (76%) prescribed daily regimens while 24% administered both daily
      and intermittent treatment. None of the private physicians prescribed exclusive
      intermittent regimen. Eighty-seven different treatment regimens were used for the
      treatment of multidrug-resistant TB (MDR-TB) with none of them prescribing
      standard treatment under RNTCP. CONCLUSION: As majority of private practitioners
      do not follow RNTCP guidelines for treating TB, there is an urgent need for their
      continued education in this area.

PMID- 23008923
TI  - Role of endobronchial electrocautery in management of neoplastic central airway
      obstruction: initial experience with seven cases.
AB  - BACKGROUND: Central airway obstruction (CAO) due to malignant and benign
      conditions is common. Tumour ablation by various techniques helps effective
      palliation of symptoms in such patients. Tumour ablation using endobronchial
      electrocautery (EBEC) with flexible bronchoscope (FB) is an established
      procedure. However, there is paucity of data from India on this topic. METHODS:
      EBEC was performed in seven patients with CAO; six of these patients had
      malignant (non-small cell carcinoma) and one had benign aetiology (tracheal fibro
      epithelial polyp) as the cause of CAO. Pre- and post-procedure assessment was
      done with the help of Speiser's symptomatic scoring. RESULTS: Mean age of the
      patients was 52.9 +/- 7.0 years; there were five males. All the patients had
      symptomatic relief after the procedure; in five of them the improvement in
      symptom scores was significant. No major complication was encountered in any
      patient. CONCLUSIONS: EBEC can be a safe, effective and cost-effective tool for
      palliation in patients with benign or malignant CAO. It is especially beneficial
      for centres where cost of bronchoscopic laser and cryotherapy is prohibitive.

PMID- 23008924
TI  - Cervical mediastinoscopy: re-evaluation of an old technique in era of new imaging
      technology.
AB  - CONTEXT: With the advent of modern anatomical and functional imaging
      technologies, application of cervical mediastinoscopy has decreased in diagnosis
      and staging of mediastinal diseases. AIM: To evaluate the usefulness of cervical
      mediastinoscopy in assessing the mediastinal disease when imaging modalities are
      non-diagnostic. SETTINGS AND DESIGN: Retrospective analysis of records of a
      tertiary care hospital. PATIENTS AND METHODS: Thirty-nine patients with
      mediastinal pathology of varied aetiologies underwent cervical mediastinoscopy.
      Pre- and post-operative diagnosis was compared. RESULTS: In 34 out of 39 cases
      (87.5%), cervical mediastinoscopy provided a confirmatory final diagnosis. One
      case had a major complication in the form of recurrent laryngeal nerve palsy.
      CONCLUSION: Cervical mediastinoscopy is useful, minimally invasive modality in a
      scenario where anatomical and functional imaging tools are non-diagnostic.

PMID- 23008925
TI  - Research in clinical sciences.
AB  - The scope and spectrum of medical research, including that in clinical sciences
      has tremendously expanded. It now extends from simple clinical observations to
      gathering of epidemiological data to the study of molecular mechanisms of
      diseases to evaluation of effects of therapeutic interventions. It is more
      meaningful to engage in multi-disciplinary and collaborative arrangements for the
      better achievements in health research. Translational approach involves the
      direct application of results of laboratory experiments to clinical use for
      benefit of patients. Besides clinical and experimental research, it is equally
      important to strengthen operational research for efficient implementation of
      health programmes and policies in the hospitals as well as in the community.
      There are several difficulties and constraints related to ethical principles,
      patient's safety, confidentiality and costs. It is critically important to adhere
      to ethical principles and guidelines to maintain the moral and social
      perspectives. It is equally important to follow the scientific research
      methodology for the maximum gains from research experiments and projects.
      Interpretation of results of clinical experiments are hardly ever unequivocal,
      hence, there is a need for repetitive studies, systematic reviews and meta
      analyses to reach definitive conclusions. It is important for busy physicians to
      adopt a scientific temper of logic and engage themselves in searching for answers
      to different research questions. It is always gainful to spare some time and
      resources for research out of a busy clinical practice. It is also worthwhile to
      go through a formal training programme in research methodology to improve
      capacity and competence to conduct meaningful research.

PMID- 23008926
TI  - Right diaphragmatic hernia in an elderly man.
AB  - A 71-year-old male presented with progressive exertional breathlessness and cough
      for the last four years. His breathlessness aggravated after a heavy meal and on
      lying down. He was a smoker, but had no co-morbidities. He did not remember any
      major trauma or surgery. Examination of the respiratory system revealed
      mediastinal shift to the left, diminished breath sounds over the whole of the
      right hemithorax and gurgling sounds all over, mainly the infrascapular area.
      Examination of other organ systems revealed no abnormality.

PMID- 23008927
TI  - Doughnut sign on FDG-PET scan in a ruptured lung hydatid cyst.

PMID- 23008929
TI  - Post-traumatic synchronous twin inter-muscular abdominal and diaphragmatic
      hernias: a rare presentation.
AB  - Simultaneous occurrence of traumatic abdominal wall hernia (TAWH) and traumatic
      diaphragmatic hernia (TDH) is uncommon. Our report documents the rare delayed
      presentation of simultaneous occurrence of TAWH and TDH in a patient who
      sustained a bicycle handlebar injury as a consequence of the bicycle he was
      riding colliding with a motorbike in a road-traffic accident. Excellent outcome
      could be achieved in this patient with surgical repair without requiring the use
      of a mesh.

PMID- 23008928
TI  - Pulmonary blastoma in a young adult.
AB  - Pulmonary blastoma is a rare but aggressive malignancy of the lung comprising
      epithelial and mesenchymal elements that resemble fetal lung tissue. This report
      described a case of an 18-year-old male who presented with cough and weight loss
      for a month. Computed tomography (CT) of the thorax revealed a large mass with
      mixed solid and cystic lesions on the right side of chest along with pleural
      effusion and mediastinal lymphadenopathy. Massive debulking was performed
      followed by chemotherapy. A biphasic pulmonary blastoma was diagnosed on
      histopathology.

PMID- 23008930
TI  - Severe lipoid pneumonia following aspiration of machine oil: successful treatment
      with steroids.
AB  - Lipoid pneumonia in children follows mineral oil aspiration and may result in
      acute respiratory failure. Majority of the patients recover without long-term
      morbidity, though a few may be left with residual damage to the lungs. We report
      a case of a two-and-a-half-year-old child with persistent lipoid pneumonia
      following accidental inhalation of machine oil, who was successfully treated with
      steroids.

PMID- 23008931
TI  - Calcified left atrial myxoma with osseous metaplasia.
AB  - An intracardiac myxoma is the most common tumour of the heart with an estimated
      incidence of 0.5 per million population per year. Extensive calcification is rare
      in these tumours. We describe a rare case of a large left atrial myxoma, visible
      on the chest radiograph, with extensive calcification and osseous metaplasia.

PMID- 23008932
TI  - Retrospective study of interstitial lung disease in a tertiary care centre in
      India.

PMID- 23008933
TI  - Breath carbon monoxide level of non-smokers exposed to environmental tobacco
      smoke.

PMID- 23008934
TI  - Pediculosis capitis revisited.

PMID- 23008935
TI  - Aquagenic wrinkling of the palms.

PMID- 23008936
TI  - Podoconiosis: the forgotten tropical lymphedema.

PMID- 23008937
TI  - Acyclovir susceptibility of herpes simplex virus isolates from transplanted and
      nontransplanted patients in Rio de Janeiro, Brazil.
AB  - Herpes simplex virus (HSV) is prevalent worldwide and known as a notorious
      opportunistic pathogen ofimmunocompromised patients. During the course of HSV
      treatment, acyclovir (ACV)-resistant HSV strains may emerge, causing many
      clinical complications. Because few studies in this area showing the presence
      and/or frequency ofACV-resistant HSV are available, the authors evaluated the
      sensitivity of HSV isolated from 3 hematopoietic stem cell transplant recipients
      and 24 normal patients observed in a University Hospital in Rio de Janeiro,
      Brazil. Twenty-seven HSV isolated in VERO cells and typed by the direct
      immunofluorescence assay were tested for their susceptibility to various
      concentrations ofACV by the dye-uptake method. The susceptibility of the HSV
      strains was expressed as ED50 (the concentration of drug reducing viral
      cytophatic effect by 50%). The sensitivity to ACV by the dye-uptake assay
      revealed that 25 samples (92.6%) were sensitive to ACV concentrations < 1.5
      microg/mL. One sample (3.7%) showed intermediate susceptibility (1.56 microg/mL)
      and one other sample (3.7%) showed resistance to ACV concentrations above the cut
      off (2 microg/mL). The presence of resistance in immunocompetent patients could
      be the result of the frequent use of ACV for the treatment of recurrence. The
      routine use of HSV susceptibility testing is fundamental in the clinical
      suspicion of resistance not only for the knowledge of the incidence of HSV
      resistance in Brazil, but also to understand the mechanism of HSV resistance.

PMID- 23008938
TI  - The asymmetric gait toenail unit sign.
AB  - The aim of this investigation was to resolve a diagnostic problem and report
      toenail unit changes attributable to shoe friction that resemble onychomycosis,
      but that are fungus-negative, and identify common skeletal causes in patients
      with an asymmetric walking gait. X-ray and clinical feet inspections were
      performed to evaluate skeletal components that change normal foot biodynamics.
      Forty-nine patients, all dermatophyte-negative, were reviewed. All patients were
      those seen in our private practice who demonstrated skeletal and toenail unit
      abnormalities such as onycholysis, nail bed keratosis resembling distal subungual
      onychomycosis, nail plate surface abnormalities, distal toe skin keratosis, a
      diagnostic nail plate shape, as well as several skeletal abnormalities. The
      clinical abnormalities of the asymmetric gait syndrome include onycholysis, nail
      bed keratosis, nail plate surface abnormalities, and a diagnostic nail plate
      shape. By the patient's history, the skeletal findings that were present worsened
      with age and, in many patients, they were familial. Onychomycosis does not lead
      to an asymmetric gait nail problem, asymmetric gait toenail does not favor
      dermatophyte infection, and not all nail dystrophies are the result of an
      asymmetric walking gait.

PMID- 23008940
TI  - Eosinophilic ulcer of the oral mucosa.
AB  - A 56-year-old woman presented with a painless lesion on the inner aspect of her
      upper lip. The clinical differential diagnoses were oral syphilitic chancre,
      tuberculosis, histoplamosis, and neoplasia. A biopsy was performed, and the
      histopathologic diagnosis revealed an eosinophilic ulcer of the oral mucosa.
      Based on this case, we discuss the history, mechanisms of pathogenesis, clinical
      manifestations, histopathology, differential diagnosis, and therapy of
      eosinophilic ulcer of the oral mucosa.

PMID- 23008939
TI  - Treatment of female pattern hair loss.
AB  - Female pattern hair loss (FPHL) as a distinctive entity was first described about
      30 years ago. The objective of this study was to perform a systematic review of
      all randomized controlled trials for treatment of FPHL. A preliminary search was
      carried out in several databases up to August 2008 to identify all randomized
      controlled trials on nonsurgical interventions for treatment of FPHL. Studies
      reporting fewer than 10 patients and non-English articles were excluded.
      Additionally, references of relevant articles and reviews were checked manually
      in search for additional sources. Among 238 citations found in the preliminary
      search, 12 fulfilled all criteria to be included in the systematic review.
      Topical minoxidil 1% to 5% for 24 to 48 weeks was shown to be effective in FPHL
      and its effect was not related to age or androgen level of patients. In addition,
      it may be effective in women with FPHL, both with and without hyperandrogenism,
      and in young and old premenopausal or postmenopausal. In patients with increased
      serum androgens, oral flutamide but not finasteride or cyproterone acetate was
      more effective than no treatment. Topical minoxidil is effective in patients with
      FPHL, with or without hyperandrogenism, but there is limited evidence for the
      efficacy of antiandrogens.

PMID- 23008941
TI  - Physiopathology of adverse cutaneous drug reactions--applied perceptions: part I.
AB  - Adverse cutaneous drug reactions are common, but their physiopathology is largely
      elusive. The authors assess various reactions to facilitate their diagnosis and
      treatment. Some of the common reaction patterns are included with the prime
      objective of highlighting their physiopathology.

PMID- 23008942
TI  - Floaters and pickups your mother never told you about.

PMID- 23008943
TI  - Entities and eponyms: two each, and a painter--"175" years on.
AB  - Time frames are always dictated by the calendar. Kaposi was born 175 years ago,
      Carl Heitzmann one year before, and lupus erythematosus (LE) just one year later.
      Strawberry Hill and its lord played not too small a role in unraveling some
      details of LE and the "hemorrhagic sarcoma to-be." Kaposi (1837-1902) lent his
      name to one of the above two syndromes, but he published extensively on both in
      the same year, same journal, and same volume (German Archives, volume 4, 1872).
      The literary "birth" of chronic discoid LE (CDLE) (1838) trails the master's by
      one year. Carl Heitzmann's birth precedes it, also by one--justification enough
      to deal with the three in one.

PMID- 23008944
TI  - Pralatrexate (Folotyn).
AB  - T-cell lymphoma accounts for 10% to 15% of all cases of non-Hodgkin lymphoma in
      the United States (approximately 5000 to 6000 cases a year). Peripheral T-cell
      lymphoma (PTCL) comprises a subgroup of rare and aggressive non-Hodgkin lymphomas
      that develop from T cells in different stages of maturity outside of the thymus.
      Cutaneous T-cell lymphoma is a subgroup that falls within the T-cell lymphoma
      population but is classified differently than other PTCLs. Most cases of CTCL are
      considered indolent and can often be treated with less aggressive therapies.
      Eight percent to 55% of CTCL cases undergo transformation, and once this
      transformation occurs, the disease acts similarly to other PTCLs and its
      classification changes to that of a PTCL. Transformed CTCL requires aggressive
      systemic therapy. Pralatrexate is the first Food and Drug Administration-approved
      drug for relapsed and refractory PTCL and has also gained compendia approval for
      treatment of CTCL. Pralatrexate is an antifolate chemotherapeutic inhibitor of
      dihydrofolatereductase. It has a high affinity for the one carbon-reduced folate
      carrier, which leads to better cellular internalization of the drug and has a
      greater antitumor effect than methotrexate. Several clinical trials have been
      conducted to evaluate the use of this drug in PTCL and other malignancies such as
      non-small cell lung cancer. This review offers focused information for
      dermatologists about pralatrexate and its use as a novel treatment for relapsed
      or refractory PTCL.

PMID- 23008945
TI  - Umbilical endometriosis in a woman with bicornuate uterus.
AB  - A 39-year-old woman presented for evaluation of a tender nodule on the umbilicus
      that had been present for 6 months. She stated that it had slowly been increasing
      in size and would occasionally open up and crust over with dried blood. Physical
      examination revealed a 4-mm firm, tender, brown papule in the umbilicus (Figure
      1). She had a history of chronic pelvic pain and exploratory laparoscopy for
      endometriosis 10 years prior, at which time the diagnosis ofa bicornuate uterus
      was made. Subsequently, hysterectomy was performed (Figure 2) at which time the
      entire umbilical lesion was excised. Histopathology revealed branching tubular
      glands in the dermis lined by stratified columnar epithelium, surrounded by small
      cells with scant cytoplasm, characteristic of proliferative-phase endometrial
      stroma (Figure 3 and Figure 4). These findings were consistent with a diagnosis
      of umbilical endometriosis (Villar's nodule). Subsequent examination revealed no
      evidence of recurrence.

PMID- 23008946
TI  - Acute generalized erythematous pustulosis occurring with Hailey-Hailey disease.
AB  - A 70-year-old woman urgently presented with severe eruptive skin dermatitis
      associated with fever and malaise 7 days after taking clindamycin for an unknown
      skin eruption. She had a 40-year-long history of well-controlled Hailey-Hailey
      disease. Physical examination revealed erythrodermic skin changes covering more
      than 80% of the patient's body surface, with hundreds of nonfollicular pustules.
      Many of the pustules fused into large bullae, involving the intertriginous as
      well as the extensor areas, sparing the mucosa. Her body temperature was 103
      degrees F. Laboratory workup was significant for neutrophilia with a white cell
      count > 10,000/mm3.

PMID- 23008947
TI  - Levamisole-induced Wegener's granulomatosis following contaminated cocaine abuse.
AB  - A 44-year-old woman with a medical history of chronic pain syndrome presented
      with a 3-day history of a painful "rash" that started on her face and spread to
      her legs. Further history revealed that she recently started a new medication,
      varenicline, 7 weeks prior to admission and had a long-standing history of
      intranasal cocaine use. Review of systems was significant for rhinitis, nasal
      congestion, joint pain, and a febrile episode 2 days prior to admission. Physical
      examination revealed centrally violaceous, tender, stellate, and retiform
      purpuric patches and plaques on her extremities, nasal dorsum, and cheeks.
      Approximately 1.0-centimeter tender purpuric nodules were noted on her bilateral
      second proximal interphalangeal joints. She was afebrile. Initial laboratory data
      revealed a mild leukopenia, normal serum urea nitrogen and creatinine without
      hematuria, and an elevated erythrocyte sedimentation rate. Further analysis
      showed a normal complement level, negative antinuclear antibody, human
      immunodeficiency virus, rapid plasma reagin, and hepatitis panel. Trace
      cryoglobenemia and a positive anti-streptolysin O were noted, along with a
      positive antineutrophil cytoplasmic antibody (c-ANCA) (> 8.0 U) and perinuclear
      antineutrophil cytoplasmic antibodies, or p-ANCA (1.5 U). The hypercoagulable
      workup was negative. A skin biopsy taken from the left thigh was consistent with
      leukocytoclastic vasculitis. After several weeks of high-dose oral prednisone
      taper, the patient's symptoms improved, but flared upon discontinuation. On
      follow-up, she admitted to frequent relapses of cocaine abuse and had developed
      tender purpuric plaques on her nose, ears, and extremities, some with ulcerations
      (Figure 1 and Figure 2). She also had significant edema and joint pain that
      limited her ambulation. Further evaluation revealed normal chest x-ray results;
      however, computed tomography of her sinuses demonstrated thickened maxillary
      sinuses consistent with subacute/ chronic sinusitis. She also developed
      hematuria. Mass spectrometry analysis ofhair and urine samples tested positive
      for cocaine and levamisole. A presumptive diagnosis of levamisole-induced
      Wegener's vasculitis was made. She was restarted on high-dose prednisone and
      methotrexate with improvement and advised to discontinue cocaine use, so as to
      avoid exposure to both substances.

PMID- 23008948
TI  - Bilateral scaly plaques in axillae: pityriasis rosea of Vidal.
AB  - A 32-year-old man was referred for acute onset of pruritic scaly eruptions in the
      axillae of 8 days' duration, which was unresponsive to topical clotrimazole. The
      lesions consisted of multiple, coalescent oval plaques of 1 cm to 6 cm in longest
      diameter (Figure 1 and Figure 2) with central clearing and typical collarette
      scales at the periphery (Figure 3). Other skin areas and mucosal surfaces were
      unaffected. His general and systemic examinations were normal. Family and past
      histories were unremarkable except for a "ring worm-like patch" on his lower
      aspect of the abdomen 4 months ago, which rapidly regressed. On further inquiry,
      he gave a history of an episode of fever, coryza, and headache 3 weeks earlier to
      his eruption on the abdomen, which resolved with conservative remedies and one
      paracetamol tablet. He remained asymptomatic until axillary lesions appeared. We
      made a provisional diagnosis of pityriasis rosea (PR). Investigations including
      scrapings for potassium hydroxide examination, complete blood cell counts,
      urinalysis, blood sugar, VDRL test, and human immunodeficiency virus antibodies
      were all normal or non-reactive. As cutaneous biopsy revealed parakeratosis,
      epidermal spongiosis, dermal inflammatory cells, and extravasated red blood cells
      (Figure 4). The eruptions cleared within 8 days, following treatment with
      mometasone furoate cream and oral desloratidine 5 mg/d, leaving post-inflammatory
      hyperpigmentation. There was no recurrence for the next 6 months of observation.
      He was later lost to follow-up.

PMID- 23008949
TI  - Nerve injury and localized skin lesions: an instance of immunocompromised
      district.

PMID- 23008950
TI  - Serpiginous, transluscent, erythematous raised tracts over the hands.

PMID- 23008951
TI  - [Age-specific peculiarities of the structure of fatal combined traumas in
      children].
AB  - The objective of this work was to study the structure and the totality of
      injuries associated with the fatal combined traumas in the children of different
      age based on the materials of forensic medical examination of children's corpses
      (115 original observations and 188 archived cases). The children died as a
      results of road traffic accidents or a fall from the height. It was shown that
      the structure of the combined trauma strongly depends on the children's age. Head
      injuries prevailed in the children under the age of 3 years whereas the frequency
      of this trauma decreased with age. On the contrary, the number of injuries to the
      chest, abdomen, pelvis, and extremities increased with the age of the children.
      Moreover, the age was an important factor influencing the extent of all injuries
      and the severity of combined traumas. These parameters increased with increasing
      age.

PMID- 23008952
TI  - [The mechanisms of formation of liver injuries associated with the blunt
      abdominal trauma].
AB  - The mechanisms of liver damage associated with the blunt abdominal trauma are
      considered based on the analysis of the literature publications. The general
      characteristic of these mechanisms and the processes underlying the development
      of liver injuries is presented. It is argued that the mechanisms underlying the
      formation of damages to the liver differ depending on the form of the traumatic
      impact, the injurious factor, and the processes leading to the destruction of the
      hepatic tissue. The main forms of traumatic impact in the case of a blunt
      abdominal trauma include the strike (blow), pressure, and concussion of the organ
      while the major traumatic factors are deformation, displacement, and "shock
      resistant effects". The mechanisms underlying tissue destruction are compression
      and stretching. These two mechanisms are responsible for the formation of
      different variants of liver destruction. The results of the study suggest the
      necessity of the search for other mechanisms of degradation of the hepatic tissue
      following a blunt abdominal trauma for the improvement of forensic medical
      diagnostics of its cause and the underlying mechanism.

PMID- 23008953
TI  - [On the forensic medical estimation of the harm to health in the case of the
      ankle joint injury].
AB  - This paper is focused on the forensic medical evaluation of the severity of the
      harm to health of the subjects suffering an ankle joint (AJ) injury. The
      retrospective data pertinent to the forensic medical evaluation of ankle joint
      injuries are presented in conjunction with the methods for their clinical
      diagnostics currently applied in traumatology and orthopedics and by the
      specialists in socio-medical expertise for the assessment of the efficacy of the
      surgical treatment, prognosis, and rehabilitation of the affected patients.

PMID- 23008954
TI  - [Forensic medical diagnostics of the form of an external impact based on the
      morphometric study of the fracture and mathematical modeling].
AB  - The authors propose a method for the diagnostics of the form of an external
      impact responsible for the fracture of long tubular bones based on the
      morphometric investigations and mathematical modeling. The study revealed
      specific morphological patterns of the fracture contour and fissures in the
      compact bone matter reflecting the character of the blow and the force of the
      accompanying pressure. A set of signs is formulated for the quantitative analysis
      of the fracture, and a morphometric study of the destroyed zone was carried out.
      The data obtained were used to develop a model for diagnostics of the form of the
      external impact. A computer software has been elaborated to promote the extensive
      application of diagnostic models in forensic medical practice.

PMID- 23008955
TI  - [The reconstruction of gunshot circumstances by means of situational forensic
      medical expertise].
AB  - The authors discuss the objective potential of situational forensic medical
      expertise for the determination of the direction and the distance of a gunshot as
      well as the position of the gun in the shooter's hand. The use of fundamental
      theoretical propositions determining the essence of the form of expertise being
      considered is illustrated by an example from forensic medical practice.

PMID- 23008956
TI  - [On the problem of traumatic shock associated with a combined injury (based on
      the materials of one forensic medical expertise)].
AB  - The author presents the results of the critical analysis of the materials of
      forensic medical expertise of a case of the serious harm to health that has led
      to involunry manslaughter. According to the expert opinion, the death resulted
      from the traumatic shock associated with the combined head and the chest injury.
      Such conclusion levels out the difference between the two accused persons and
      their "contribution" to the extent and severity of the inflicted damage to the
      victim's body; thereby, it equalizes the degree of their guilt and criminal
      responsibility. The present study showed that such interpretation of
      tanatogenesis associated with the combined injury is erroneous. The death of the
      injured person resulted from cerebral coma that developed following a severe
      craniocerebral injury as a constituent component of the combined trauma. It is
      emphasized that the thorough investigation of tanatogenesis based on the reliable
      elucidation of the immediate cause of death makes it possible to avoid poorly
      substantiated expert conclusions and their potential dire legal consequences.

PMID- 23008957
TI  - [The estimation of defects in the provision of medical care to the victims of
      road traffic accidents at the stage of hospitalization].
AB  - The retrospective analysis of 2,657 medical records of the victims of road
      traffic accidents that took place in the city of Chelyabinsk is presented. It was
      shown that the majority of defects of the medical care at the stage of
      hospitalization were related to its poor organization whereas the defects of
      diagnostics, the treatment proper, and its continuity were less significant.
      Taken together, defects of the medical care were responsible for 25.3% of the
      fatal cases. The study revealed the most important factors that may enhance the
      potential risk of unfavourable outcomes of the treatment of the consequences of a
      road traffic accident by 2-9.5 times.

PMID- 23008958
TI  - [The detection of amphetamines in urine samples using immunochromatographic test
      strips].
AB  - This study has demonstrated the possibility of using immunochromatographic test
      strips for the reliable qualitative detection of amphetamine and methamphetamine
      in the urine samples at a cut-off level of 300 ng/ml. The test strips obtained
      from different manufactures are shown to be slightly different in terms of
      specificity as appears from the frequency of cross-reactions with various
      pharmaceutical products and narcotic drugs. Also, the use of the
      immunochromatographic strips makes it possible to determine amphetamine in a
      range of concentrations from 100 to 1000 ng/ml by measuring the intensity of test
      line colour with the help of a TotalLab TL120 programmer and special scanning
      programs. The analysis for amphetamine using the NrcoStop (Osiris S)
      immunochromatographic strips failed to confirm the presence of this substance in
      the urine samples from the subjects who had drunk 0.5 l of energy drinks, such as
      Adrenaline RUSH, Red Bull, and Burn. It means that the presence of amphetamine in
      the urine should not be attributed to the consumption of such drinks.

PMID- 23008959
TI  - [The application of the solid phase extraction technique to the analysis of blood
      for the presence of narcotic and pharmaceutical substances].
AB  - This paper is devoted to the application of the solid phase extraction (SFE)
      technique based on the use of the SampliQ Evidex cartridges prepacked with a
      mixed phase "granular" sorbent for the screening of pharmaceuticals and narcotic
      substances in the whole blood by means of gas chromatography and mass
      spectrometry. It is concluded based on the available data that the solid phase
      extraction technique has advantages over the traditional liquid-liquid extraction
      and may be used for the purpose of forensic chemical examination carried out in
      Bureaus of Forensic Medical Expertise.

PMID- 23008960
TI  - [The determination of clozapine for the forensic chemical study of the cadaveric
      blood, urine, and liver using high performance liquid chromatography].
AB  - The method for the determination of clozapine during chemical studies of
      cadaveric blood, urine, and liver (kidneys) has been developed based on the use
      of high performance liquid chromatography. Clozapine losses were estimated at 40
      60% with the fractional uncertainty below 10-11% and the detection limit of 0.001
      mg%. An algorithm for the estimation of the quality of clozapine isolation and
      the results of analysis of individual samples is proposed.

PMID- 23008961
TI  - [The methods for the protection against counterfeit medications. Part 1. The
      estimation of the quality of metoprolol succinate substance and tablets from
      different manufacturers in terms of "identity" and "active ingredient content"].
AB  - This paper was designed to report the results of analysis of metoprolol succinate
      substance and tablets obtained from two manufacturers, Akrikhin (Russia) and
      AstraZeneca (Sweden). The analysis was performed by spectroscopy in the near IR
      region and followed by the chemometric treatment of the data obtained. The method
      was used to confirm the "identity" of metoprolol succinate tablets. The approach
      to distinguishing the differences between pharmaceutical dosage forms produced by
      different manufacturers is proposed. Also, the method for the qualitative
      determination of metoprolol succinate in the pharmaceutical formulations has been
      developed.

PMID- 23008962
TI  - [Professional errors in practical neonatology associated with blood transfusion].

PMID- 23008963
TI  - [Emilii Fedorovich Bellin: the triumph and tragedy].

PMID- 23008964
TI  - [The overview of research on toxicological (forensic) chemistry based on the
      materials of the abstracts of dissertation theses. The forms and modes of
      information].
AB  - The authors discuss the system of information about investigations on
      toxicological (forensic) chemistry carried out for obtaining the scientific
      degree as it has formed in this country. They present a review and a list of
      theses and their abstracts in this discipline defended during the period from
      1936 to 2010. The analysis of the themes of the studies is performed with
      reference to the dynamics of preparation of the theses in the Soviet and post
      Soviet periods.

PMID- 23008966
TI  - [The 6th scientific and practical conference of young scientists and specialists,
      members of the Moscow Society of Medicolegists, "Forensic medical science and
      practice"].

PMID- 23008965
TI  - [Inter-regional scientific and practical conference "Topical problems of forensic
      medicine, medical law, and biomedical ethics"].

PMID- 23008967
TI  - Research fatigue among Tongans in Aotearoa: an exploratory study introducing the
      Fei'umu research method for empowering the researched.
AB  - INTRODUCTION: There has been a number of references in the literature to over
      research and research fatigue, but rarely have the concepts been empirically
      investigated, and never for Pasifikans. There have been claims that researchers
      have built careers out of the 'natural experiment situations of the Pacific with
      minimal benefits to the researched, e.g. the Tongans. In response, an exploratory
      investigation into the New Zealand Tongan communities' understanding of and
      participation in, research, (HRC Seeding Grant No. 11/529), was conducted.
      METHOD: We consulted 2 different church meetings in Auckland (approximately 50
      people in each group). We also engaged in talanoa/discussions of the issues with
      5: church leaders from different denominations; Tongan researchers; business
      owners; and 5 community leaders from Auckland, Wellington, Hamilton and
      Christchurch, respectively. RESULTS: The study found, that the Tongan communities
      are subjected to a variety of research, information, and data gatherings, from a
      myriad of agencies. The respondents used a variety of mechanisms to avoid
      discomfort, get rid of researchers as expediently as possible, including;
      heliaki, white lies, sarcasm, or give expected answers, thus confirming research
      fatigue. The interviews and surveys employing the Tongan language and ethnic
      specific research approaches were preferred, especially for sensitive issues. The
      study suggests that ownership of the research process will improve the robustness
      of the data collection, and the community ownership of research outcomes.
      CONCLUSION: The presence of research fatigue will threaten robust data collection
      and ownership of research findings. This paper discussed research fatigue and its
      dangers, and suggest ways to address this problem, before researchers are driven
      further from the researched communities and the utility of research knowledge.

PMID- 23008968
TI  - Cancer incidence in four pacific countries: Tonga, Fiji Islands, Cook Islands and
      Niue.
AB  - BACKGROUND: We have established and/or upgraded cancer registries in four Pacific
      countries, a region where few cancer registries exist. We report age-standardised
      cancer incidence in Tonga (2000-2005), Fiji (2002-2005), Cook Islands (2000-2005)
      and Niue (2000-2005), and in Pacific people in New Zealand (2000-2005). METHODS:
      In each country we identified incident cancer cases by reviewing hospital
      discharge, death registration, cancer registration records, and pathology
      reports. The primary site and morphology data were coded using ICD-0, and age
      standardised incidence rates were calculated. RESULTS: Age-standardised cancer
      incidence rates for Pacific people in New Zealand (315 per 100,000 person-years
      in females, 379 in males) were similar to those for New Zealand overall (322 in
      females, 404 in males); incidence rates were lower in the Pacific, with rates of
      195 and 151 per 100,000 person-years for females and males respectively in Tonga,
      231 and 126 in Fiji, 165 and 142 in the Cook Islands, and 228 and 131 in Niue.
      However, some specific cancers were elevated in the Pacific including cervical
      cancer (16 per 100,000 in Tonga, 51 in Fiji, 17 in Cook Islands, and 26 in Niue
      compared with 10 in Pacific people in New Zealand, and 8 in New Zealand overall),
      liver cancer (rates of 8, 5, 19, 0, 7, and 2 respectively) and uterine cancer
      (rates of 24, 18, 47, 19 and 12 respectively). CONCLUSIONS: Cancer incidence in
      the Pacific is lower than for Pacific people living in New Zealand. Environmental
      rather than genetic factors are most likely to explain these patterns, and cancer
      incidence in the Pacific is likely to increase to rates similar to those in New
      Zealand as the region becomes more 'westernised' The high rates of cervical
      cancer and liver cancer in the Pacific indicate an important role of

PMID- 23008969
TI  - Body image and its relation to obesity for Pacific minority ethnic groups in New
      Zealand: a critical analysis.
AB  - The stimulus behind most of the early investigations into Pacific or Polynesian
      peoples' body image, particularly those that looked to compare with Western or
      Westernised groups, is the assumption that Pacific peoples valued and therefore
      desired very large bodies, and in relation to obesity-risk, this is a problematic
      cultural feature to have. This may be driven by popular anecdotes which are
      captured in the title of one such study "Do Polynesians still believe that big is
      beautiful?" To the author's knowledge, no research in Pacific peoples' body image
      has been conducted in the New Zealand (NZ) context by Pacific researchers. This
      study makes a contribution to the literature gap and more importantly through an
      emic viewpoint. A critique of the current literature is provided below which
      calls into question the initial catalyst behind earlier investigations which have
      led to the perpetuation of particular types of body image research for Pacific
      groups. Using mixed-methods, the specific objective of this study was to describe
      the behaviours, beliefs and values of Pacific adolescents and their parents, that
      are related to body image. A self-completion questionnaire was administered to
      2495 Pacific students who participated in the New Zealand arm of the Obesity
      Prevention In Communities (OPIC) project. Sixty-eight people (33 adolescents and
      35 parents) from 30 Pacific households were interviewed in the qualitative phase
      of the study. This study found Pacific adolescents and their parents did not
      desire obesity-sized bodies but desired a range of average-sized bodies that met
      their Pacific-defined view of health. It is not clear whether body image research
      makes any meaningful contribution to obesity prevention for Pacific people, given
      the cultural-bounded nature of the concept "body image" which sits communication
      and understanding between obesity interventionists and all healthcare workers
      generally and Pacific communities. For obesity interventions to be acceptable and
      useful for Pacific people, they must be responsive to the beliefs and desires of
      these communities.

PMID- 23008970
TI  - Young people's perceptions and experiences of physical activity in Apia, Samoa.
AB  - Physical inactivity is one of the main risk factors contributing to the
      prevalence of lifestyle diseases in Samoa. Lifestyle diseases are now the major
      causes of death in this Pacific island. As part of a Master's thesis in Sport and
      Leisure Studies, a study was carried out in Apia, Samoa, 2007 to investigate
      perceptions and experiences of physical activity at five secondary schools and a
      tertiary institution. A total of 801 respondents aged 13-50 years were surveyed.
      The survey data were analysed to explore the respondents' perceptions about
      physical activity and health, perspectives about barriers that stopped them from
      being active and sources of encouragement for being active. Most respondents
      reported a positive attitude towards physical activity and indicated that
      physical activity was important to improve health, get fitter and lose weight.
      Although, many respondents believed they were physically active, they did not
      meet the recommended national physical activity guidelines. Respondents reported
      a number of barriers to physical activity such as cultural, environmental and
      discomfort factors. More than half of them wanted to be more active and almost
      56% wanted to lose weight, but need help and encouragement from friends and
      community. A coordinated response engaging all health sector partners is
      recommended to improve physical activity in the community. Such efforts would
      ensure that everyone accepts the responsibility of preventing and controlling the
      prevalence of lifestyle diseases.

PMID- 23008971
TI  - Domestic violence as a major cause of trauma in Western Province, Papua New
      Guinea.
AB  - BACKGROUND: Domestic violence is endemic in PNG accounting for 90% of female
      trauma. It is a significant cause of morbity in the country and a drain on
      already scarce healthcare resources. Few studies have assessed the scale of the
      problem in rural areas. AIM: To assess the scale of the problem in the Western
      Province and the views of the victims to try and identify the underlying causes.
      METHODS: Trauma presentations to the outpatient department and trauma admissions
      to Kiunga hospital were audited over a four week period in September 2009.
      Patients admitted with domestic violence-related injuries were then asked a short
      questionnaire. RESULTS: 16 patients (15 females, 1 male) presented to Kiunga
      hospital with domestic violence-related injuries. 13 of these patients were
      admitted. In this time only one other female was admitted for acute trauma thus
      over 90% of female trauma admissions were due to domestic violence. The victims
      were not as accepting of the problem as other studies have suggested. Victims all
      reported that the police failed to act when they reported an incident.
      CONCLUSIONS: Domestic violence is a major public health problem in PNG.
      Increasing the presence of women in law enforcement agencies and law reform to
      offer more support to victims is needed to improve the problem.

PMID- 23008972
TI  - Well-nourished women in a Solomon Islands society with a biased sex ratio.
AB  - This study reports on the growth and nutritional status of females in Roviana
      (population 12 235), Solomon Islands, where there are fewer surviving females
      than males in all age groups (male/female = 1.10; Solomon Islands Government
      2000). Anthropometric measurements were performed for 1243 voluntary participants
      from seven villages. The results showed that females were better nourished than
      males; weight-forage z-scores, for instance, were better for females than those
      for males throughout all age groups, with statistical significance in the
      following age groups: younger than 5 years, 10-14 years and 15-19 years. The same
      pattern was also observed for adults. Results suggest that gender inequality
      might not be caused by social discrimination.

PMID- 23008973
TI  - Indigos in Hawai'i: a phenomenological study of the experience of growing up with
      spiritual intelligence.
AB  - There is a special group of children around the world who have high intelligence
      and intuition, healing abilities, and a strong spiritual connection with God, yet
      these children are often mislabeled as having behavior disorders. Little is known
      from scientific research about the Indigo phenomenon in America, although many
      countries, especially among indigenous populations, are familiar with Indigo-like
      children. The purpose of studying these children when they are adults is to
      better understand these children when they are older and advance behavior health
      sciences by increasing awareness of the Indigo phenomenon and learning about
      their lived experiences. This phenomenological study explored the lived
      experiences of 10 adult Indigos (> or = 18+ years old) on the island of Oahu,
      Hawai'i (7 females, 3 males; mean age = 52.4 + SD). Through in-depth semi
      structured personal interviews, the experiences of these adults were analyzed and
      interpreted to identify the common experiences faced during childhood, what
      worked for their assimilation into society, and recommendations for parents,
      educators, and health professionals on how to work with Indigos. Bioenergy field
      (aura) photographs of each participant were also taken. Statements related to the
      phenomenon were placed into themes, coded, and categorized as the investigators
      reached a consensus of common themes. Seven primary themes and nine secondary
      themes emerged from the findings. The primary themes were: grandmother/mother had
      a similar gift; guided by a higher power to heal self and others; felt
      "different" or misunderstood; did not openly share their unique abilities; having
      challenges with partner relationships; history of abuse/violence or frequently
      disciplined; and use of intuition at work and/or school. Secondary themes
      included: Using Hawaiian and cultural healing methods; everyone has a degree of
      intuition and the use of intuition to know when to see a doctor or not; various
      unique abilities from body and multiple careers; mental health institutions, and
      financial struggle. Self reports on participants' life purpose, their unique
      abilities, and being misunderstood were also collected. It was concluded that
      Indigos felt mislabeled or misunderstood throughout their lives in spite of their
      belief that their life purpose was to help humankind.

PMID- 23008974
TI  - 'Getting rid of tobacco...that's the key': strong feelings of Pacific
      policymakers in New Zealand about tobacco, and smoking around children.
AB  - AIM: To further explore the views of New Zealand-based Pacific policymakers on
      smoking in general, smoking in public and private spaces, and smoking around
      children. METHODS: Key informants (n = 18) were recruited and interviewed by
      Pacific interviewers during May-October 2008, in person or by phone. RESULTS: The
      interviews revealed a great depth of feeling about smoking in general, smoking in
      public places, and smoking around children. There was considerable variance of
      opinion on the extent to which smokefree areas should be extended, with some
      informants reluctant to interfere with smokers' "choices" There was a general
      consensus that adults' right to smoke should be limited by social and ethical
      responsibilities to children. CONCLUSIONS: The strong feelings found in favour of
      tobacco control by some of the interviewees is notable. Mobilising such feelings
      may help facilitate further progress for advancing tobacco control for Pacific
      communities in New Zealand and for assisting tobacco control in other South
      Pacific island nations.

PMID- 23008975
TI  - Rheumatic fever in Samoa: education as prevention.
AB  - The incidence of acute rheumatic fever (ARF) and its sequela rheumatic heart
      disease (RHO) is disproportionately high among the children of Western Samoa.
      Basic symptoms of ARF include fever, joint pain, and a sore throat. The condition
      of strep throat, if left untreated, may initiate an immune response which can
      damage the heart and become RHD. Primary prevention currently consists of
      educating locally trained nurses to detect strep throat and dispense antibiotics
      as necessary. The concept of targeting proximal caregivers with prevention
      information has not been explored. Health behavior theories offer methodology for
      the development, implementation, and evaluation of health promotion programs.
      This study incorporates the interpersonal level of the ecological model (EM) in
      conjunction with the four elements of the social change model (SCM) which are
      critical thinking, fundamental skills, cultural sensitivity, and action. The
      purpose of this study was to test the hypothesis that an educational prevention
      program can be effective in disseminating pertinent information regarding ARF
      prevention. This study followed a matched-pairs, same subject design, using a pre
      /post-survey as the observational tool in which to measure the effectiveness of
      the presentation. The question that targeted trust of health care workers showed
      a statistically significant increase (p = < .0001) from approximately 50% in the
      pre-survey to 73% in the post-survey. The question regarding antibiotic treatment
      was slightly significant for the pre-survey (p = 0.0428), but showed increased
      statistical significance for the post-survey (p -< 0.0001). Responses targeting
      the contagious factor changed in significance between the pre- and post-survey
      from p = .009 to p = < .001. The response change for the question targeting the
      possibility of a child contracting a sore throat as school changed from p = .0123
      to p = < < .0001. These findings support the use of a basic and inexpensive
      educational prevention program.

PMID- 23008976
TI  - The epidemiology of dengue fever in Palau.
AB  - BACKGROUND: Dengue fever has been a longstanding problem in Palau, and Public
      Health programs were implemented in 2001 to conduct surveillance for cases of the
      disease. Epidemiologic analysis of dengue fever cases in Palau is needed to
      describe disease occurrence in Palau and to help target prevention and control
      efforts. METHODS: Case data were collected from the Palau Ministry of Health's
      Reportable Disease Surveillance System. Descriptive epidemiology was performed on
      the case data, and spatial analysis was used to assess the distribution of dengue
      fever cases in Palau. RESULTS: Between January of 2001 and June of 2006, 676
      cases of dengue fever occurred in Palau, and sporadic outbreaks without
      seasonality were noted. Characteristics of the case population included being
      male (57.8%), being under the age of 20 (mean age = 23.4 years), being Palauan
      (88.2%), having an indoor occupation (91.7%), and having no history of travel
      outside of Palau during the estimated exposure period (96.3%). Most cases also
      lived in urban areas of Palau (92.0%), and the disease rate was significantly
      higher in urban areas compared to rural areas (3941.8 versus 1175.7 cases per
      100,000, respectively for the 5.4-year study period; p = 0.0007). CONCLUSION:
      This study supports the idea that dengue fever is still endemic in Palau. Control
      and prevention measures should be continued, and targeted toward urban areas and
      populations at increased risk of this disease.

PMID- 23008977
TI  - The epidemiology of leptospirosis in Palau.
AB  - BACKGROUND: Leptospirosis has been a longstanding problem in Palau, and Public
      Health programs were implemented in 2000 to conduct surveillance for cases of the
      disease. Epidemiologic analysis of leptospirosis cases is needed to describe
      disease occurrence in Palau and to help target prevention and control efforts.
      METHODS: Case data were collected from the Palau Ministry of Health's Reportable
      Disease Surveillance System. Descriptive epidemiology was performed on the case
      data, and spatial analysis was used to assess the distribution of leptospirosis
      cases in Palau. RESULTS: Between May of 2000 and June of 2006, 81 cases of
      leptospirosis occurred in Palau. Characteristics of the case population included
      being male (72.8%), being Palauan (70.4%), having an indoor occupation (71.0%),
      and living in an urban area of Palau (80.3%). It was also found that non-Palauan
      cases were significantly more likely to die of leptospirosis compared to the
      Palauan cases (p = 0.0018). Non-Palauan cases were significantly more likely to
      live in rural areas of Palau (p = 0.0001). There was no significant difference in
      the disease risk when comparing urban and rural areas. The crude disease risk for
      Palau is 401.9 (95% Cl 313.8-489.9) cases per 100,000 for the 6.2-year study
      period, and the average annual risk was 65.2 per 100,000. CONCLUSIONS:
      Leptospirosis continues to be present in Palau, and prevention and control
      measures should be continued and targeted toward specific states and hamlets of
      Koror. Furthermore, non-Palauan populations should be targeted for interventions
      to prevent more severe outcomes of this disease.

PMID- 23008978
TI  - Investigation of an outbreak of cholera among Chuukese residents of Guam, 2005.

PMID- 23008979
TI  - Nutritionally acquired immune deficiency syndromes (NAIDS): common but often not
      diagnosed early.
AB  - It has been the perception in some pacific island countries that the textbook
      presentation of kwashiorkor has decreased in incidence possibly due to improved
      public health services and economic development of the country. However, the
      diagnosis and treatment is nonetheless crucial to child survival. This paper
      discusses the clinical courses of 2 children with kwashiorkor whose presentation
      were not of that taught to medical students or even junior doctors. Their
      presentation together with their subsequent nutritionally acquired immune
      deficiency syndrome (NAIDS) is illustrated to raise awareness of the complexities
      in diagnosis and management of such patients.

PMID- 23008980
TI  - Left-sided congenital abdominal wall defect and intestinal malformation--a rare
      case.
AB  - A case report of a female newborn with a rare congenital abdominal wall defect
      associated with intestinal malformation. To our knowledge, only a few case
      reports of left sided congenital abdominal wall defect with this type of
      anomalies have been reported in the world literatures and this is the first in
      Fiji. This case brought numerous challenges to the team in terms of defining the
      pathology, role of undertaking surgery, providing supportive and nutritional
      therapy to a neonate and the ethical dilemma with the management in a developing
      country.

PMID- 23008981
TI  - Is kava alcohol?: The myths and the facts.
AB  - This paper addresses the misconception that kava is an alcoholic substance. After
      a brief introduction as to what prompted the writing of this, I follow by
      discussing kava's cultural importance to Pacific peoples, and then compare kava
      'intoxication' with alcohol intoxication. The paper concludes with a discussion
      of the historical influences that have promoted some of the misconceptions
      surrounding kava. Ultimately the paper demonstrates that kava and alcohol are
      entirely different kinds of beverages with different effects, and that lingering
      misconceptions can be seen as a 'colonial hangover'.

PMID- 23008982
TI  - Drug and alcohol use in Fiji: a review.

PMID- 23008983
TI  - An evaluation of a nutrition intervention in Kapinga Village on Pohnpei,
      Federated States of Micronesia.
AB  - The people of Kapinga Village are suffering from chronic diseases as a result of
      their lifestyles and eating habits, similar to many Pohnpeians. Kapinga Village
      is an urban area on the island of Pohnpei, Federated States of Micronesia,
      settled by people from Kapingamarangi, a remote atoll. The villagers have limited
      access to traditional staple foods, including breadfruit, banana, and taro,
      fruits, vegetables, and other healthy foods. The Island Food Community of Pohnpei
      (IFCP) carried out several nutrition interventions in Kapinga Village to prevent
      disease, including promotion of physical activity through growing local food, a
      nutritious diet of local foods, cooking classes, container gardening, and
      charcoal oven workshops. This study evaluated the effect of those interventions
      on dietary intake. A 7-day Food Frequency Questionnaire (FFQ) was administered in
      June-July, 2010 to participants from 68 households and data were compared to 2009
      baseline data. Qualitative data were collected and analyzed to identify salient
      themes that were associated with changes in dietary intake. The FFQ data
      indicated that there was an increase in consumption of local fruits and
      vegetables compared with the baseline. Qualitative data revealed that
      participants viewed the interventions positively. The data also revealed that
      some of the new foods and drinks consumed were those already available in the
      village, but for which their uses had not previously been known (such as banana
      flower and hibiscus tea). Such improvements are likely to be sustainable.
      Recommendations are for more education, in the Kapingan language if possible, and
      future research to determine what culturally appropriate interventions are still
      needed to improve nutrition in Kapinga Village.

PMID- 23008984
TI  - Improving integration and coordination of funding, technical assistance, and
      reporting/data collection: recommendations from CDC and USAPI stakeholders.
AB  - BACKGROUND: Current US Federal funding mechanisms may foster program silos that
      disable sharing of resources and information across programs within a larger
      system of public health services. Such silos present challenges to USAPI
      communities where human resources, health infrastructure, and health financing
      are limited. Integrative and coordinated approaches have been recommended. The
      CDC Pacific Islands Integration and Coordination project was initiated by the CDC
      Division of Cancer Prevention and Control (DCPC). The project aim was to identify
      ways for the CDC to collaborate with the USAPI in improving CDC activities and
      processes related to chronic disease. This article focuses on recommendations for
      improving coordination and integration in three core areas of health services
      programming: funding, program reporting/data collection and analysis, and
      technical assistance. METHOD: Preliminary information on challenges and issues
      relevant to the core areas was gathered through site visits, focus groups, key
      informant interviews, and other sources. This information was used by stakeholder
      groups from the CDC and the USAPI to develop recommendations in the core
      programming areas. Recommendations generated at the CDC and USAPI stakeholder
      meetings were prepared into a single set of recommendations and stakeholders
      reviewed the document for accuracy prior to its dissemination to CDC's National
      Center for Chronic Disease Prevention and Health Promotion programs management
      and staff. RESULTS: Key recommendations, include: (1) consideration of resources
      and other challenges unique to the USAPI when reviewing funding applications, (2)
      consideration of ways to increase flexibility in USAPI use of program funds, (3)
      dedication of funding and human resources for technical assistance, (4) provision
      of opportunities for capacity-building across programs and jurisdictions, (5)
      consideration of ways to more directly link program reporting with technical
      assistance. CONCLUSIONS: This project provided a unique opportunity for CDC and
      USAPI stakeholders to share diverse perspectives on challenges to public health
      programs in the USAPI. Despite diverse experiences, the final set of
      recommendations reflected a high level of concordance between USAPI and CDC
      stakeholders. Recommendations have informed or reinforced actions initiated by
      the DCPC, including the dedication of funds for leadership institutes aimed at
      enhancing USAPI capacity for sustainable, integrated regional and jurisdictional
      cancer control infrastructure. Such efforts are an important beginning, but more
      remains to be done. Indicated is the need for continuous dialogue and
      collaboration. While this project focused on the USAPI, our results may be
      relevant to those interested in inter-organizational collaborations, medically
      underserved areas, public health services programs, and community-based
      participatory approaches.

PMID- 23008985
TI  - "Australia's nurses and midwives. You couldn't be in better hands.".

PMID- 23008986
TI  - Pressure injury prevention: do patients have a role?

PMID- 23008987
TI  - Primary and secondary amputation in critical limb ischemia patients: different
      aspects.
AB  - The TASC II working group reports on primary amputation incidence rates vary
      between 12 and 50 per 100,000 per year. The primary amputation rate does not only
      depend on co-morbidities like diabetes and PAD, but also on local factors like
      the regional availability of vascular surgeons and interventional radiologists
      and their case load. Further-more, several studies could show that increasing
      revascularisation rates have drastically reduced amputation rates in the US, with
      a 50% decrease in amputation rates during a 10 year study period and a
      corresponding increase in surgical and endovascular revascularisation rates. An
      analysis of national and state US databases confirmed a drop in major amputations
      and open surgical revascularisations, in favour of an increase in endovascular
      interventions. The same study observed an increase in minor amputations during
      the same period. However, it remains unclear whether this trend is a consequence
      of the increased usage of endovascular procedures in high-risk patients who are
      unfit for open surgery or of earlier endovascular intervention in less critical
      lesions. This review gives an overview of the incidence, indication, amputation
      level finding and outcome of major amputations performed in critical limb
      ischemia (CLI) patients.

PMID- 23008988
TI  - Pituitary incidentaloma: to operate or not to operate?
AB  - The wide use of sophisticated imaging techniques has led to the discovery of
      asymptomatic pituitary lesions, which are called 'incidentalomas'. Their global
      prevalence averages 10% whereas that of macroadenomas (> 10 mm) is less than 1%.
      The most frequently encountered lesions are non-functioning adenomas followed by
      Rathke's cleft cysts. Physiological pituitary hypertrophy is also frequent in
      young women. Silent functioning adenomas especially prolactinomas can be found
      among incidentalomas. Hypopituitarism appears to be more frequent in larger
      lesions but can occur in microadenomas (< 10 mm). The incidence of tumour growth
      is higher in macroadenomas and solid lesions in comparison with microadenomas and
      cystic lesions. The baseline evaluation should include in all patients a complete
      history and physical examination, a screening for hormone hypersecretion and
      hypopituitarism and a visual field examination if the lesion abuts the optic
      nerves or chiasm. If there is hormone hypersecretion, an appropriate treatment is
      indicated (dopamine agonists for prolactinomas and surgery for tumours producing
      GH, ACTH or TSH). If there is hypopituitarism, adequate hormone replacement
      therapy is required. According to recent guidelines, the indications for surgery
      of non-functioning incidentalomas include a visual field deficit, other visual
      abnormalities such as ophtalmoplegia or a lesion abutting the optic nerves or
      chiasm on magnetic resonance imaging (MRI). Regarding the follow-up of
      incidentalomas not meeting the criteria for surgery, the following tests should
      be performed: MRI at 1 year for micro-incidentalomas, at 6 months for macro
      incidentalomas and then less frequently if unchanged in size, visual field
      examination for lesions enlarging to abut or compress the optic nerves or chiasm
      (6 months and yearly) and endocrine testing for macro-incidentalomas (6 months
      and yearly). Nowadays, data are insufficient to suggest the routine use of
      medical therapy in non-functioning tumours. Pituitary radiotherapy may be useful
      as an adjunctive treatment for tumour remnants growing progressively.

PMID- 23008989
TI  - Complications after conservative treatment of blunt liver trauma in children.
AB  - BACKGROUND: Nonoperative treatment is the gold standard approach to treat blunt
      liver trauma (BLT) in hemodynamically stable children. The purpose of this study
      was to evaluate the incidence, risk factors, timing for appearance, diagnostic
      modalities, management and outcome of hepatic complications secondary to such
      approach. METHODS: This retrospective study included children admitted at
      Montpellier University Hospital for BLT over a 10-year period. All
      hemodynamically stable children were initially conservatively treated. RESULTS: A
      total of 51 children underwent nonoperative treatment for BLT during the study
      period. The success rate was 94.1% (48/51). Three patients (5.9%) presented 13
      complications related to hepatic injuries and required secondary surgical
      treatment. These 3 patients presented grade 3 or higher liver lesions. Others
      factors identified as predictive of complications included initial hemodynamic
      instability (responding to the first resuscitative measures), presence of
      peritoneal irritation at first examination, severe hemoperitoneum, an initially
      low haemoglobin level (< 8.5 g/dl) and need for important transfusions during the
      first 48h (> 10 cc/kg). The median interval for appearance of complications was
      19 days after injury (range 1-60 days). Complications were successfully treated
      using minimally invasive techniques in 69.2% of cases (9/13). The rest of the
      complications (30.8% : 4/13) were surgically treated. All children included in
      our study had favourable outcomes (follow-up 1-54 months). CONCLUSIONS: This
      series fully validates conservative approach of BLT in hemodynamically stable
      children. Complications of such approach are uncommon; many can be successfully
      treated using minimally invasive techniques with very satisfying results.

PMID- 23008990
TI  - Life-threatening side effects of malabsorptive procedures in obese patients
      necessitating conversion surgery: a review of 17 cases.
AB  - BACKGROUND: Malabsorptive surgery (MAS) can cause huge weight loss but is also
      known for its serious side effects. We investigated whether conversion surgery is
      an effective treatment for MAS-induced complications. METHODS: We searched our
      hospital database for patients who underwent conversion surgery after MAS. Any
      complication was recorded till time of conversion. The conversion techniques and
      their effect on the course of the patients were analyzed and compared to the
      situation after MAS. RESULTS: We identified 17 patients who suffered a wide range
      of complications after biliopancreatic diversion (BPD) (n = 11), biliopancreatic
      diversion with duodenal switch (BPD-DS) (n = 4), or distal gastric bypass (D-GBP)
      (n = 2). After a (mean +/- SD) period of 6.0 +/- 3.6 years the MAS was either
      converted to a gastric bypass (GBP) in 6 patients or an elongation of the common
      limb (ECL) in 9 patients. Two conversions were atypical. After a (mean +/- SD)
      follow-up of 2.4 +/- 2.5 years the majority of blood test results improved. The
      incidence of most complaints diminished except abdominal discomfort, critical
      illness polyneuropathy, need for total parenteral nutrition (TPN), wheelchair
      dependency, and asthenia. One patient died of irreversible liver failure after 3
      liver transplantations. Two patients died of cachexia. The preferred conversion
      technique is still unclear. CONCLUSIONS: MAS can cause invalidating and life
      threatening side effects. If there are signs of incipient deterioration in organ
      function and/or nutritional status, conversion surgery should not be delayed.
      Although we have the impression that early conversion causes better outcome, many
      patients experience lifelong postoperative complications.

PMID- 23008991
TI  - Indocyanine green angiography for evaluation of gastric conduit perfusion during
      esophagectomy--first experience.
AB  - BACKGROUND: A complication of esophageal surgery is leakage at the anastomosis
      site and one of the factors involved in this complication is poor blood flow in
      the distal portion of the tube. The aim of this study was to evaluate the
      feasibility of indocyanine green fluorescence imaging as a method of determining
      the perfusion of the gastric conduit after esophagectomy. METHODS: We analysed 15
      consecutive patients who underwent transhiatal esophagectomy (THE) due to cancer.
      All of the patients had reconstruction of the gastrointestinal tract using the
      gastric conduit. Before performing the anastomosis, the blood flow in the area of
      the tube was evaluated using intravenous indocyanine green and observing its
      vascular flow with a camera equipped with an infrared laser. RESULTS: In all
      cases it was possible to visualize the vascular flow of indocyanine green within
      the region of the gastric tube. The fluorescence imaging system showed vascular
      insufficiency of the distal gastric conduit in 4 patients--in all of these
      patients the anastomosis was performed end-to-side and there was no subsequent
      leak. Leakage at the anastomosis site was observed in 1 patient (6.66%). The leak
      was observed in the 9th postoperative day, despite visualization of a good
      vascular supply of the tube. CONCLUSIONS: Indocyanine green fluorescence imaging
      of gastric tube allows for intraoperative modifications, but it must be noted
      that the patient's comorbidities and general health may also increase the risk of
      anastomosis leakage.

PMID- 23008992
TI  - Surgical treatment of mediastinal cysts: report on 29 cases.
AB  - AIM: Mediastinal cysts are rare, forming 12-18% of all primary mediastinal
      tumors. The purpose of this study is to evaluate type, clinical properties,
      treatment modalities, and results of mediastinal cystic neoplasm in the light of
      available literature. PATIENTS AND METHODS: We retrospectively investigated 29
      patients who were diagnosed and surgically treated for mediastinal cysts in our
      clinic between January 1996 and May 2011. RESULTS: Sixteen (55.2%) patients were
      male and 13 (44.8%) were female. The average age of the patients was 36.5 +/-
      22.1 (17-77 years old). The mediastinal cysts comprised 11 (37.9%) bronchogenic
      cysts; seven (24.1%) hydatid cysts; four (13.8%) benign cystic teratomas; three
      (10.3%) pericardial cysts; one (5.3%) thymic cyst; one (5.3%) cyst of the
      thoracic duct; one (5.3%) enteric cyst; and one (5.3%) lymphangioma. Approach
      methods were thoracotomy in 18 (62.1%) cases; video-assisted thoracoscopicsurgery
      (VATS) in seven (24.1%) cases; median sternotomy in three (10.3%) cases; and
      anterior mediastinotomy in one case. Postoperative observations during the follow
      up period showed chylothorax in one patient; pleural effusion in one patient; and
      the recurrence of a bronchogenic cyst in one patient five years after the
      operation. Postoperative mortality did not occur in any case. The average
      postoperative hospitalization period was 7.3 days (2-14 days). CONCLUSION: A
      surgical approach to mediastinal cysts offers histological analysis, pathological
      diagnosis, curative treatment, and prevention from complications.

PMID- 23008993
TI  - Diaphragm valves reduce gastroesophageal reflux following cardiomyotomy for
      patients with achalasia.
AB  - BACKGROUND: This study was designed to investigate the effect of a novel surgical
      method on cardia sphincter function and complication rates after Heller's
      cardiomyotomy for patients with achalasia. METHODS: Forty-eight patients (19
      males, mean age 34.0 +/- 10.5 years, range, 12-58) were included in this study. A
      spindle diaphragm valve was used in the surgery to rebuild the cardiac sphincter
      function. The efficacy of the surgery was determined by clinical assessment of
      symptoms and lower esophageal sphincter pressure (LESP) measurements. Barium meal
      examination was also used to evaluate the efficacy. RESULTS: The mean LESP before
      surgery was 41.3 +/- 11.6 mmHg. It was reduced to 16.8 +/- 3.7 mmHg and 17.5 +/-
      2.5 mmHg 3 and 12 months after surgery (P < 0.01). All patients were free of
      symptoms such as swallow difficulties or acid reflux during the follow up.
      However, barium swallow examination showed that 1 patient had mild reflux after
      the surgery. Clinical symptom scores on swallow difficulties/obstruction was
      reduced from 2.5 +/- 0.65 before surgery to 0.06 +/- 0.24 12 months after the
      surgery (P < 0.01). CONCLUSION: A spindle diaphragm valve used with Heller's
      cardiomyotomy was associated with a very low incidence of post-surgical
      complications, such as gastroesophageal reflux. This technique may be used in
      treating all patients with achalasia.

PMID- 23008994
TI  - The acute-phase response in differentiating sepsis from inflammation in neonates
      who require abdominal surgery.
AB  - INTRODUCTION: In neonates, the influence of surgery on the inflammatory response
      has not been fully characterized and it remains difficult to differentiate an
      inflammatory response from sepsis. In this study, we evaluated changes in
      interleukin-6 (IL-6) and C-reactive protein (CRP) in neonates undergoing
      different major abdominal surgeries who had a normal postoperative course without
      infection. MATERIAL AND METHODS: In total, 43 neonates undergoing major abdominal
      surgery owing to congenital malformations involving the gastrointestinal tract,
      and who did not show blood culture positivity were enrolled in the study. As a
      control group, 40 neonates with proven sepsis were enrolled in the study over the
      same period. Blood samples for IL-6, CRP, and white blood cell count (WBC)
      determination were drawn before surgery and 48, 96, and 144 h [postoperative days
      (POD) 2,4, and 6] after surgery. RESULTS: There was a statistically significant
      increase in IL-6 concentrations on POD 2 compared with preoperative levels (p <
      0.05). After POD 2, IL-6 levels decreased to preoperative levels. There was a
      statistically significant increase in CRP concentrations on POD 2, 4, and 6 (p <
      0.05). Levels of CRP tended to be higher after surgery, and began to fall by the
      6th day, but were still statistically higher than preoperative levels. In the
      sepsis group, CRP concentrations on day 6 were lower than in the surgery group (p
      < 0.05). White blood cell counts did not show statistically significant
      differences preoperatively versus postoperatively. CONCLUSIONS: In contrast to
      previous studies, our results show high levels of IL-6 on POD 2 and CRP on POD 6.
      It is important to differentiate between the diagnoses of sepsis and
      postoperative inflammation, because of the need to treat the infection. High
      levels of IL-6 and CRP are not always associated with sepsis after major
      abdominal surgeries, but may instead be associated with the inflammatory response
      and multiorgan dysfunction. Further studies are needed to better differentiate
      sepsis from inflammatory responses in patients undergoing other surgeries.

PMID- 23008995
TI  - The influence of the law on patient's rights on the practice of the Flemish
      paediatricians anno 2010.
AB  - BACKGROUND: The law on patients' rights in Belgium was issued in 2002. The new
      legal framework recommends the establishment of a true dialogue between physician
      and patient, and it assigns decisive priority to the adolescent rather than to
      the physician or his parents. PURPOSE AND METHODS: The purpose of this study is
      to map the current interpretation of the paediatrician and the realisation of the
      law in practice. The answers of 117 Flemish paediatricians to an anonymous
      questionnaire were analyzed. RESULTS: Only 7.8% of the paediatricians state that
      they know the law well. 15.5% experience the law as a burden. 20.9% have adopted
      a different attitude when rendering care to adolescents under impulse of this
      law. 6.2% say they do not strictly follow the law. 27.8% think that the
      emancipating thought is too far-reaching. Most paediatricians apply protocols to
      interpret the traditional values that are stamped as being good medical practice:
      high quality care (81%), free patient's choice (70.7%), adequate pain control
      (77.4%). On the other hand paediatricans seldom dispose of procedures regarding
      the more emancipated amenities in the law such as obtaining informed consent
      (16.4%), access to the medical file (24.8%) and safe-guarding the privacy (13%).
      In practice most of the physicians offer the possibility of a free choice in 80%
      of the cases. All questioned physicians strive for a high quality care, for
      adequate pain control and for a careful maintained medical file. 79.1% of the
      physicians transfer to the parents all medical information regarding the
      adolescent. Proper experience and expertise (80.7%), case by case completed, are
      most often used as the basis for the judgment about the competence of the
      adolescent. From the patient's side, little advance is taken to exercise his own
      rights. Barely 1% of the adolescents consulting a paediatrician use their legal
      right to autonomously consent to a medical intervention. In barely 0.16% access
      is requested to the medical file. Practically no complaints are received
      regarding the law on patients' rights (0.1% in intramural setting, versus 0.001%
      extramural). CONCLUSION: The law on patients' rights is, after 8 years of
      issuance, badly penetrated in the paediatric practice. On the one hand this is
      due to a poor knowledge of the law as well from the side of the physician as from
      the side of the adolescent and/or his parents. On the other hand 42.2% of the
      paediatricians experience difficulties with the practical interpretation of the
      law because of the lack of applicable guidelines. An important obstacle is the
      fact that more than a quarter of the paediatricians do not agree with the in the
      law foreseen autonomy of the adolescents. For that reason, paediatricians
      urgently need to be instructed in these matters. It is the moral duty of the
      Society of Paediatrics to organize workshops on these matters and develop clear
      guidelines concerning this law. Proper application of the legal context, the
      handling of the watertight procedures and the necessary communication in this
      respect is indispensable for the confidence and will lower the barrier for
      adolescents to use the healthcare system.

PMID- 23008996
TI  - Misleading diagnosis of renal artery stenosis by magnetic resonance angiography
      in a patient with primary aldosteronism.
AB  - A 24-year-old woman presented with severe hypertension. A diagnostic evaluation
      for secondary hypertension was undertaken. A duplex ultrasonography followed by a
      magnetic angiography suspected fibromuscular dysplasia. Unexpectedly, a contrast
      enhanced angiography performed for renal angioplasty showed normal renal
      arteries. Primary aldosteronism was then evoked on the basis of decreased plasma
      renin and increased plasma aldosterone and aldosterone/renin ratio. After a CT
      scan disclosed a left adrenal tumour, the patient underwent a left laparoscopic
      adrenalectomy. Pathological findings confirmed a benign adrenocortical adenoma.
      Blood pressure and aldosterone levels were normalized after surgery. Thus,
      clinicians should be aware of false-positive results of magnetic resonance
      angiography that could hide other causes of secondary hypertension.

PMID- 23008997
TI  - Pneumoretroperitoneum, bilateral pneumothorax and emphysema following endoscopic
      biliary sphincterotomy.
AB  - We report a case of pneumothorax, subcutaneous emphysema and
      pneumoretroperitoneum after an endoscopic sphincterotomy. A 40-yr-old woman
      presented with dyspnea immediately after she had undergone an endoscopic
      retrograde cholangiopancreatogram for a residual stone in common bile duct. On
      arrival to our hospital, she complained about severe dyspnea and on examination
      subcutaneous emphysema was discovered. A CT scan was conducted and showed a right
      sided pneumothorax, a pneumoretroperitoneum in the peritoneal cavity. We
      recommended to the patient an immediate laparotomic exploration. We discovered a
      duodenal perforation in which we sutured it with accompanying pyloric exclusion,
      double truncular vagotomy and gastroenteroanastomosis. Endoscopic retrograde
      cholangiopancreatogram (ERCP) is a popular procedure for biliary and pancreatic
      diseases, but it can cause severe complications such as intestinal perforation.
      Besides perforations, air can spread through the abdominal cavity,
      retroperitoneum, mediastinum, and the soft tissues of the neck, eventually
      causing pneumothorax. Early recognition and appropriate management is crucial for
      optimal results.

PMID- 23008998
TI  - Cardiac paraganglioma: diagnostic work up and review of the literature.
AB  - Paraganglioma of the heart are potentially invasive, highly vascularized tumors
      for which complete resection may be curative. Derived from the cardiac wall in
      most instances, resectability can be assessed after integration of the data
      provided by MRI in T2 sequence, and coronarography. A fully documented case of a
      large cardiac pheochromocytoma of the left atrium and AV groove is reported and
      the pertinent literature on the subject is here presented.

PMID- 23008999
TI  - Malignant fibrous tumor of the pleura: case report and literature review.
AB  - Solitary fibrous tumours (SFT) of the pleura are uncommon and are incidental
      findings or discovered in patients with non-specific respiratory symptoms. We
      report a case of a 74 year old man diagnosed with a mesenchymal pleural neoplasm,
      associated with typical hypertrophic osteoarthropathy, referred to as Pierre
      Marie-Bamberg syndrome. As reported in the literature, complete surgical
      resection is the gold standard for treatment of such lesions and recurrences.
      Radiotherapy and chemotherapy are of limited value in the curative treatment of
      pleural SFT. In our case surgical excision of the mass was performed. After a
      disease-free period of 3 years a second intervention was necessary because of
      recurrence. Until now our patient is free of complaints and no signs of
      reappearance were noted. Based on our experience and on literature findings we
      would like to underline the importance of regular long-term follow-up because of
      the substantial risk of recurrence.

PMID- 23009000
TI  - A Merkel cell carcinoma presenting as a solitary lymph node metastasis without a
      primary lesion. Report of a case and review of the literature.
AB  - Merkel cell carcinoma is an uncommon, aggressive neuroendocrine tumour of the
      skin. At presentation regional lymph nodes are involved in approximately one
      third of the patients. In this report a patient is presented in whom Merkel cell
      carcinoma presented as a solitary lymph node metastasis with an unknown primary
      skin lesion. The diagnosis of unknown primary merkel cell carcinoma including the
      use of immunohistochemical markers and treatment options based on data from the
      literature are discussed.

PMID- 23009001
TI  - [Genetically modified food--great unknown].
AB  - Genetically modified food (GMF) creates evident threat to consumers' health. In
      spite of assurances of biotechnologists, DNA of transgenic plants is instable,
      so, synthesis of foreign, allergenic proteins is possible. Due to high trypsin
      inhibitor content the GMF is digested much more slowly what, alike Bt toxin
      presence, increases probability of alimentary canal diseases. Next threats are
      bound to the presence of fitoestrogens and residues of Roundup pesticide, that
      can diminish reproductiveness; and even lead to cancerogenic transformation
      through disturbance of human hormonal metabolism. In spite of food producers and
      distributors assurances that food made of GMF raw materials is marked, de facto
      consumers have no choice. Moreover, along the food law products containing less
      than 0.9% of GMF protein are not included into genetically modified food.

PMID- 23009002
TI  - [Dilatation of the left atrium as one of the indicators of worse prognosis in
      patients treated with intermittent hemodialysis].
AB  - Cardiovascular diseases are the most frequent cause of death in patients
      undergoing treatment with hemodialysis (HD). Echocardiography is the established
      method in diagnosis and searching for HD patients with an increased risk of death
      from cardiovascular events. The aim of the study was to show parameters, obtained
      also in the echocardiographic examination, which are helpful to distinguish
      persons with the worse prognosis among the group of HD patients. MATERIAL AND
      METHODS: Observation was done in 56 patients. Echocardiographic examination was
      performed at baseline before and after HD. The observation lasted 26.3 +/- 13.6
      months. The analysis included the effect of the patient demographic
      characteristics, clinical and echocardiographic parameters: gender, age, duration
      of renal replacement therapy, body mass index, presence of ischemic heart
      disease, chronic heart failure, presence of valvular defects, hypertension,
      pharmacological therapy, systolic and diastolic left ventricular function, the
      size of the left and right atrium, atrial volume changes that occur due to
      decreased blood volume during HD treatment on the death risk. RESULTS: In the
      group of 56 patients significantly worse survival was shown in persons with
      symptoms of cardiac failure. After 3 years of the observational study in the
      group without diagnosis of chronic cardiac failure 90.9% patients survived,
      whereas in the group with diagnosis of cardiac failure 51.0% (p = 0.020). In the
      group of patients with diagnosis of severe valvular disease 14.3% survived,
      whereas in the group without severe valvular disease 66.1% survived, (p = 0.009).
      Among patients without diagnosis of arterial hypertension 30.0% survived; in the
      group with diagnosis of arterial hypertension 65.9% (p = 0.016). In the group of
      patients with left atrial dimension > 50 mm all patients died, whereas in the
      group of patients with left atrial dimension < or = 50 mm 62.6% (p = 0.010)
      survived. CONCLUSIONS: HD patients with worse survival prognosis can be
      identified by echocardiographic examination showing risk factors which were
      severe valvular disease and dilatation of the left atrium.

PMID- 23009003
TI  - [The impact of cochlear implant (CI) on the process of phonation and quality of
      life of patients with pre- and postlingual deafness].
AB  - Cochlear Implant (CI) is the most advanced method of treatment in receptive type
      of deafness and profound hearing loss. Good functioning auditory organ plays a
      significant role not only in auditory perception but also in the process of
      phonation, giving the possibility of good realization of the process of verbal
      communication. The aim of the study is to assess the quality of voice and life in
      adults with pre- and postlingual deafness treated using cochlear implant.
      MATERIAL AND METHODS: Twenty six patients with pre- (group I) and postlingual
      (group II) deafness deriving no benefit from hearing aids were included into the
      study. Voice quality was assessed using subjective and objective methods. The
      endoscopic (VLS) and stroboscopic (VLSS) examination of the larynx and the
      acoustic voice analysis were carried out. The quality of life was assessed using
      the Nijmegen Cochlear Implant Questionnaire (NCIQ). Examinations were conducted
      before implantation and 6 months after activation of speech processor. RESULTS:
      In the subjective and objective assessment of voice quality the improvement was
      registered in both groups. The effects were less spectacular in prelingual
      patients. In this group of patients the subjective assessment of voice quality
      and stroboscopic examination confirmed the hypofunctional type of dysphonia. In
      postlingual patients the hyperfunctional type of dysphonia was registered what
      was confirmed by the analysis of acoustic parameters of voice. The improvement of
      quality of life was observed in both groups of patients after implantation.
      CONCLUSIONS: The voice quality was improved after implantation in both analyzed
      groups. In patients with postlingual deafness values of parameters of voice
      quality assessment were closed to physiological. Results of the subjective
      assessment of voice quality were confirmed by objective examinations and the
      acoustic voice analysis. Rehabilitation with cochlear implant gave the
      opportunity for active participation in private and social life, improving the
      quality of life in patients with pre- and postlingual deafness.

PMID- 23009005
TI  - [Fear-driven cesarean section on request].
AB  - Traditionally, women gave birth surrounded by other, experienced women. Modern
      women not only require continuous support during labor, but they also want to
      have a part in decision-taking. That is why some of them, regardless of how much
      or how little medical knowledge they have, want to decide about the way of birth
      on their own. The aim of this study was to find the underlying cause of the
      growing percentage of cesarean sections and cesarean sections on request and to
      find an answer to the question of what can be done to reduce that number.
      MATERIAL AND METHODS: A survey was conducted among 100 nulliparas between 38 and
      40 week of pregnancy who were determined to give birth in a natural way, and
      among 50 nulliparas, in the same gestational age, who requested cesarean section.
      RESULTS: The analysis of our survey shows that request for cesarean section in
      12% of cases resulted from fear of labor pain, more than before were declared 2%.
      After they were informed about methods of reducing labor pain and guaranteed that
      those methods would be available, as many as 52% of pregnant women who had
      previously requested cesarean section changed their mind and wanted to give birth
      in a natural way (this could reduce cesarean section rate about 52%, p<0.05), and
      42% (of the total) wanted to have epidural anesthesia. CONCLUSIONS: Better access
      of pregnant women to information about pharmacological and non-pharmacological
      methods of reducing labor pain, coupled with the availability of those methods,
      can reduce the number of cesarean sections on request even by half. In the group
      of pregnant women determined to have cesarean section, one in four would give it
      up if they had access to epidural anesthesia, and one in ten if they had access
      to non-pharmacological methods of reducing labor pain (mainly acupuncture).

PMID- 23009004
TI  - [Vaccination against Streptococcus pneumonia and knowledge about it in the
      cardiology and general practitioners patients].
AB  - Streptococcus pneumoniae is a reason of many infectious diseases, from prosy
      respiratory tract infections to the grave bacterial hematosepsis which often is a
      cause of patients death. Infection spreads with droplets or sometimes by direct
      contact. Symptomatic Staphylococcal infections most often unfold as a otitis,
      sinusitis, broncho-pneumonia and lobal pneumonia or as a chronic obstructive
      pulmonary disease, bronchial asthma aggravation or they can be the cause of many
      other illnesses like: meningitis and encephalitis, endocarditis, epicarditis,
      peritonitis, arthritis and hematosepsis. The aim of the study was to evaluate
      anti-streptococcal vaccinations and to analyze cardiology patients and General
      Practitioners patients knowledge about Streptococcus pneumoniae. MATERIAL AND
      METHODS: There were 312 Cardiology and General Practitioners patient's from
      Outpatients Clinic in Katowice included to the study. Additionally there were
      national registers analyzed involving anti-streptococcal vaccination and
      streptococcal infections data from years from 2006 to 2009. Informations about
      anti-streptococcal vaccination and data evaluating knowledge about streptococcal
      infections problems were obtained from the poll made especially for this study.
      RESULTS: Results of the study showed, that patient's knowledge about anti
      streptococcal vaccination is very poor. From 312 patients included to the study
      only 16 were vaccinated and 118 persons had no knowledge about Streptococus
      pneumoniae. Data from the national registers showed, that in the years 2006-2009
      the invasive form of streptococcal infection had similar number of patients - 273
      and 274 respectively - in Silesia, 28 and 26 patients respectively. CONCLUSIONS:
      The knowledge about anti-streptococcal vaccinations is very poor and a number of
      people vaccinated small. There is the need to provide more information to rise
      the number of vaccinated persons, especially in the group of increased risk and
      consequently reduce worker absenteeism in the work and financial loss.

PMID- 23009006
TI  - [Drugs acting on the heart-conductive system in suicide attempts].
AB  - The prevalence of diseases of the cardiovascular system is the cause of their
      frequent use, and thus, easy availability of drugs acting on the cardiovascular
      system, including people they do not require. In Poland, annually are taken from
      4.5 to 5.5 thousand suicide attempts, about 3.7% of them due to excessive
      consumption of pharmaceuticals. The aim of this study was to analyze patients who
      for suicidal attempts ingested drugs acting on the cardiac conduction system, and
      to study performed diagnostic and therapeutic procedures and obtained results.
      MATERIAL AND METHODS: The study included all hospitalized in the years 1995-2010
      in the Department of Anesthesiology and Intensive Care patients after excessive
      suicidal ingestion of drugs acting on the heart conductive system. The study
      group comprised a total of 40 patients aged from 15 to 70 years. RESULTS: Suicide
      attempts in the study group were mostly taken by the lonely people and by the
      subjects with disturbed adaptation. The patients were unconscious mainly after
      ingestion of psychotropic drugs. From the 40-person group of patients after
      suicidal ingestion of drugs affecting the conduction system of heart eight
      patients (20%) required respirator. It has not been shown that any group of drugs
      significantly more frequent induced respiratory distress requiring mechanical
      assistance. Rhythm and conduction disturbances during hospitalization occurred in
      15 patients (38%), of which 12 (30%) required temporary endocardial stimulation.
      The study revealed the longest ventricular stimulation need in patients after
      consumption of calcium channel blockers. Blood pressure in half of the patients
      was depressed, and 15 of them (38%) required the use of pressor amines. From the
      40-person group 2 people died (one patient after ingestion of 4000 mg of
      propranolol and the other after eating 6000 mg of verapamil). Patients who died
      differed from the other patients with in younger age, longer time elapsed since
      the consumption of drugs to their hospitalization, during admission they had
      undetectable blood pressure, bradycardia, and decreased serum potassium levels.
      The remaining 38 patients (95%) were discharged from the Department of
      Anesthesiology and Intensive Care. CONCLUSIONS: Attempts to take his own life
      with the use of drugs in the cardiac conduction system in the study group were
      taken by a lonely and adaptive disturbances. The most commonly used preparations
      for suicide were beta-adrenergic receptors blockers, whereas hemodynamic
      abnormalities, arrhythmias and conduction disturbances were observed more
      frequently after the drugs that block calcium channels. In patients with life
      saving use in suicide attempts important role in addition to medication dosage
      plays an elapsed time of their consumption and speed of action taken to remove
      and prevent absorbtion the poison", as well as close supervision in the intensive
      care unit.

PMID- 23009007
TI  - [Anxiety associated with parachute jumping].
AB  - The aim of the study was to estimate an influence of parachute jumps on anxiety
      among professional soldiers from air-borne forces. MATERIAL AND METHODS: The
      investigation was carried out on 46 professional soldiers from 16 Air-Borne
      Battalion, patients of outpatient department of 4495 Military Unit, men at 20 to
      45 age, healthy--admitted to parachute jumping in air-borne forces. They were
      divided on groups according to a knowledge and an experience in parachuting. In
      order to estimate the level of nervous tension and mental stress, personal
      questionnaires in accordance with STAI were carried out on free day, day of
      parachute jump and 24h after jump. RESULTS: The results show the influence of
      parachute jumps on the parameters of psychological stress.

PMID- 23009008
TI  - [Epidemiology and risk factors of the cervical squamous cell carcinoma].
AB  - Neoplasm of the cervix, especially squamous cell cancer, is one of the most
      common malignancy of female genital organs. It etiology is complex; however,
      human papilloma virus (mostly HPV type 18, 16 and 45) infection seems to be the
      most important one. Other risk factors include: early sexual initiation, multiple
      pregnancies and labors, concomitant infections (Chlamydia trachomatis, Neisseria
      gonorrhea, HSV2 - herpes simplex virus) of the genital tract, AIDS,
      immunosuppressive therapy, smoking and low socioeconomic status. The incidence of
      cervical cancer is particularly high in developing countries, while in countries
      where government founding for the prevention and health education is high, the
      diseases is significantly less likely to occur. The incidence and mortality rate
      of the cervical cancer can be substantially reduced by systematic screening
      cytological examinations. For such reason a liquid-based cytology is currently
      preferred. Implementation of HPV vaccines decrease the risk of infection, but
      effect on rate of the cervical cancer has to be confirmed in long-time
      prospective clinical and epidemiological studies.

PMID- 23009009
TI  - [Role of positron emission tomography in diagnosis and monitoring of
      sarcoidosis].
AB  - Positron emission tomography is a three-dimensional nuclear imaging technique. It
      is often use in diagnosis of neoplasms, disease of cardiovascular and central
      nerve system. There are some researches which show role of this method in
      diagnosis and monitoring some of pulmonary disease. This paper sums up current
      reports about role of positron emission tomography in diagnosis and monitoring
      of: occupancy of organs and treatment in sarcoidosis. It shows limited capability
      to differentiating sarcoidosis from chest malignancy at use 18-fluorodeoxyglucose
      as radiolabel and result of promising research which show usefulness 18
      metyltyrosine in this range. We summarise papers which present benefits of PET in
      determination of advancing disease especially in multi-systemic and atypical
      cases. Advantage of PET over present use radiological patechnique in defining of
      sarcoidosis activity allows using it in monitoring of treatment with standard
      therapy and help in determination of usefulness of new drugs. Future large
      randomised studies could help in using this still expensive method in wide range
      of patient to diagnose and monitoring of sarcoidosis and other nowadays unused
      recommendation.

PMID- 23009010
TI  - [The alterations of proteins glycosylation in rheumatic diseases].
AB  - The alterations in glycosylation of serum glycoproteins were reported in several
      pathological conditions including rheumatic diseases. The many studies
      demonstrated the occurrence of some differentially glycosylated plasma
      immunoglobulins, especially IgG in rheumatoid arthritis. The most characteristic
      features are the decrease in galactose content, the presence of N
      acetylglucosamine and the increase in fucose content. The structure of
      oligosaccharides attached to the antibody Fc region affect the pharmacokinetics
      and antibody effector functions of antibody-dependent cellular cytotoxicity and
      complement-dependent cytotoxicity. The changes in immunoglobulin glycosylation
      was suggested to be important in the etiology of rheumatoid athritis and
      correlated with the disease severity. In addition to impaired glycosylation of
      imunoglubulins, in rheumatic diseases exist the disturbances in glycosylation of
      both acute-phase and non acute-phase response, such as alpha-1 acid glycoprotein,
      haptoglobin and alpha-2 macroglobulin. The alterations in glycosylation of these
      glycoproteins were also correlated with the disease activity.

PMID- 23009011
TI  - [Depression in metabolic syndrome].
AB  - The paper is concentrated on a problem of coexisting two syndromes: metabolic and
      depression. The importance of glucocorticoids, especially a role of glucose and
      proteins in metabolism, is presented here. The paper also presents the criteria
      of metabolic syndrome developed by: the USA National Cholesterol Education
      program Adult Treatment, World Health Organization and International Diabetes
      Federation. Common existence of both metabolic and depression syndromes was taken
      into consideration in the light of the latest research. A significance of
      environmental factors (a life style) in metabolic syndrome was indicated. Basing
      on the investigation results, a frequency of the occurrence of the individual
      components of the metabolic syndrome and their correlation with depression
      syndrome was evaluated. The correlation between laboratory studies in both sexes
      and revealing depression symptoms were highlighted. The relationship between both
      unhealthy diet and little activity and the development of depression syndrome
      ware observed. Finally, an advantageous role of psychological distress as a
      factor protecting against development of the individual components of metabolic
      syndrome was emphasized.

PMID- 23009012
TI  - [Human orgasm from the physiological perspective--part II].
AB  - In contrast to the male orgasm, female orgasm is characterized by high
      variability and diversity, not only in the general population, but also during
      the life. Women experience sexual pleasure on many levels: physical, emotional,
      spiritual and intellectual. Sexual functioning of women and men is determined by
      many factors. A strong correlation between the state of subjective arousal and
      genital response (erection) is typical for men. In the case of women important
      role played: emotions, cognitive interpretation of the situation, age, self
      esteem and previous sexual experiences. Among women experience orgasm during
      intercourse or masturbation is not a goal in itself. Modern approach to the
      phenomenon of orgasm and sexual education of women, make absence of orgasm as a
      failure. It becomes a source of low self-esteem, less self-confidence or sense of
      lack of attractiveness.

PMID- 23009013
TI  - President-elect looks to the challenge ahead.
AB  - Next month's Healthcare Estates conference and exhibition will see a new IHEEM
      President take up the reins, as Greg Markham, BEng (Hons) CEng FIHEEM MIET MBIFM,
      unusual in being one of very few private sector employees to have taken on the
      role (he is currently technical services director at G4S Integrated Services
      [UK]), succeeds Paul Kingsmore. HEJ editor, Jonathan Baillie, met Greg Markham in
      London to find out more about his professional background, career, and interests,
      talk through the key challenges he believes healthcare estates and engineering
      personnel will face as the NHS enters a new era, and discuss how he plans to use
      the experience and expertise gained during an extremely varied 25-year career in
      estates and facilities management and engineering--both within and outside
      healthcare--to good effect in the new role.

PMID- 23009014
TI  - Considering the 'known unknowns'.
AB  - Speaking at a recent IHEEM seminar focusing on some of the key water hygiene and
      safety, and waterborne infection prevention issues, facing healthcare estates/
      engineering personnel responsible for 'large, complex' water systems, Dr Nick
      Hill, technical director of the Water Hygiene Centre, examined some of the
      continuing areas of uncertainty over the characteristics and properties of
      different Legionella serogroups, the colonisation levels necessary to cause
      illness in individuals of varying susceptibility, potential sources, and the
      materials most likely to harbour the bacterium, and discussed effective methods
      for killing the organism, and preventing its spread. HEJ editor, Jonathan
      Baillie, reports.

PMID- 23009015
TI  - Training tomorrow's estates teams.
AB  - According to Stephen Lloyd, lead facilities management (FM) tutor at
      Gloucestershire-based training provider, Eastwood Park, 'a combined 150 years'
      invaluable estates experience has just disappeared from one hospital in the past
      month', and, as many experienced healthcare estates personnel retire, and the
      sector struggles to attract replacements, the situation is being replicated in
      many hospitals UK-wide. HEJ editor, Jonathan Baillie, spoke to Stephen Lloyd, and
      to several of his training colleagues for a new 'Essentials for Estates' course
      being launched next month by Eastwood Park to address some of the 'skills gaps',
      to discover where they feel the biggest challenges lie for tomorrow's healthcare
      estates teams, and where the training focus should be.

PMID- 23009016
TI  - Ensuring condensate recovery efficiency.
AB  - According to steam system specialist, Spirax Sarco, 'condensate contains about a
      quarter of the energy of the steam from which it came--a significant amount of
      heat available to an energy centre'. Ensuring that existing condensate recovery
      systems are as efficient as possible is therefore 'key' to reducing energy centre
      costs, the company says. Paul Mayoh, product manager, Spirax Sarco, considers
      ways to ensure that as much condensate as possible is re-used.

PMID- 23009017
TI  - Dirty ducting's numerous hazards.
AB  - Hospitals and other healthcare facilities that do not regularly inspect, monitor,
      and, if necessary, clean, both their general ventilation ductwork and 'often
      forgotten' kitchen grease extract systems could not only be putting occupants'
      health, and even lives, at risk, but could also face heavy financial penalties,
      significant damage to buildings, and even prosecution, a leading ductwork
      cleaning specialist has warned. In many cases, Richard Norman, managing director,
      and Simon Vann, business development director, at Indepth Hygiene Services, told
      HEJ editor, Jonathan Baillie, the cost of having a grease extract ductwork system
      professionally cleaned could be 'relatively insignificant', while the 'generally
      higher' outlay required for thorough clean of a hospital-wide general ventilation
      ductwork system may well be spreadable over months, or even years.

PMID- 23009018
TI  - Challenges of moving in large equipment.
AB  - Getting new, and often heavy, medical equipment, such as MRI and CT scanners,
      into busy working hospitals, is often highly challenging--from a structural,
      mechanical, electrical, and logistical standpoint. Stuart Beardwell, BEng (Hons)
      CEng MIStructE, an associate director at consulting engineers, Crofton, who has
      overseen the moving of heavy medical equipment into many UK hospitals, discusses
      the key issues to consider, explains how time and costs can be saved, and
      considers how to manage such work without excessively disrupting everyday
      clinical activities.

PMID- 23009019
TI  - Towards achieving the 'quiet hospital'.
AB  - Alex Krasnic BEng MSc MIOA, senior acoustician at ZBP Acoustics, the acoustics
      division of consulting engineer, Zisman Bowyer & Partners, explores practical
      steps towards achieving 'the quiet hospital' without compromising other design
      elements, while also recognising that acoustic design features can sometimes be
      seen to conflict with certain healthcare protocols.

PMID- 23009020
TI  - Modern shutters can be a thing of beauty.
AB  - Roger Humphreys, managing director of Charter Specialist Security, a specialist
      supplier of 'built-in' roller shutters, argues that, with the ability to be
      effectively 'integrated' into the fabric of a building, and availability in a
      wide range of 'exciting' colours and finishes, modern security shutter systems
      are a world away from the 'often ugly and purely functional' designs many will
      immediately picture when they consider using such items to protect their
      properties and their contents against attack.

PMID- 23009021
TI  - State-of-the-art HDU's critical importance.
AB  - Phil Green, senior project engineer at independent building services company,
      Shepherd Engineering Services (SES), describes SES's creation a new 'state-of-the
      art', 4.5 million sterling pounds, high dependency unit (HDU) at The James Cook
      University Hospital, Middlesbrough. Completion of the 16-bed HDU, part of a wider
      South Tees Hospitals NHS Foundation Trust investment programme to remodel and
      enhance the hospital's facilities, follows last September's completion, also by
      SES, of the Endeavour Unit (HEJ - November 2011), a new oncology satellite
      building built as a key element of the Trust's 30 million sterling pounds
      expansion and redevelopment of its Radiotherapy Unit at the Middlesbrough
      hospital.

PMID- 23009022
TI  - The health impact of demolition dust.
AB  - Dr Claire Holman, Principal at ENVIRON, a global consultancy which works with
      clients 'to manage their most challenging environmental and health and safety
      issues, and attain their sustainability goals', considers the impacts on health
      of dust released during demolition work, and the measures that can be taken to
      mitigate them. Drawing on a recent case study, she explains how ENVIRON prepared
      a comprehensive site dust management plan (DMP) to minimise fungal spore release
      during the demolition of a building located adjacent to residential accommodation
      for child leukaemia patients and their parents. She also considers some of the
      lessons learned, in terms of actions that 'worked well' and those that could,
      with hindsight, have been undertaken 'better'.

PMID- 23009023
TI  - Prevalence and risk factors of metabolic syndrome in the Korean population-
      Korean National Health Insurance Corporation Survey 2008.
AB  - AIM: To determine the factors affecting the prevalence of metabolic syndrome in
      younger and older Koreans. BACKGROUND: Metabolic syndrome, in combination with
      other, interrelated predisposing factors, is a risk factor for cardiovascular
      disease. In Korea, the prevalence of this syndrome, like those of other chronic
      diseases, has increased continually in recent years. DESIGN: This is an analytic,
      descriptive cross-sectional study. METHODS: This survey targeted 690,283
      examinees that had undergone a medical examination on a life transition period
      performed by the National Health Insurance Corporation from January-December
      2008. For the purpose of this study, the diagnosis of metabolic syndrome was
      based on the criteria of the American Heart Association and the Heart, Lung, and
      Blood Institute. The relationship between the risk factors and prevalence rate
      was shown using a multiple logistic regression model. RESULTS: The prevalence of
      metabolic syndrome was 24.8% in the 40 year olds and 40.8% in the 66 year olds.
      Among the younger adults, the prevalence in women was only 0.57 times that in
      men. A multiple logistic regression analysis demonstrated that heavy obesity and
      family history of cardiovascular disease are the strongest independent predictors
      of metabolic syndrome among younger and older Koreans. CONCLUSION: As a
      management strategy, a nursing intervention strategy for the improvement of
      lifestyle factors including self-care through proper diet and exercise should be
      developed and implemented.

PMID- 23009024
TI  - Stereoselective C-glycoside formation with 2-O-benzyl-4,6-O-benzylidene protected
      3-deoxy gluco- and mannopyranoside donors: comparison with O-glycoside formation.
AB  - Unlike alcohols, the reaction of C-nucleophiles with 2-O-benzyl-4,6-O-benzylidene
      protected 3-deoxy-gluco- and mannopyranosyl thioglycosides is highly
      stereoselective providing the alpha-C-glycosides in the gluco-series and the beta
      C-glycosides in the manno-series. Conformational analysis of nucleophilic attack
      of putative intermediate glycosyl oxocarbenium ions suggests that the observed
      selectivities for C-glycoside formation can be explained by preferential attack
      on the opposite face of the oxocarbenium to the C2-H2 bond and that eclipsing
      interactions with this bond are the main stereodetermining factor. It is argued
      that the steric interactions in the attack of alcohols (sp(3)-hybridized O) and
      of typical carbon-based nucleophiles (sp(2) C) on oxocarbenium ions are very
      different, with the former being less severe, and thus that there is no a priori
      reason to expect O- and C-glycosylation to exhibit parallel stereoselectivities
      for attack on a given oxocarbenium ion.

PMID- 23009025
TI  - Cross-informant agreement between parent-reported and adolescent self-reported
      problems in 25 societies.
AB  - We used population sample data from 25 societies to answer the following
      questions: (a) How consistently across societies do adolescents report more
      problems than their parents report about them? (b) Do levels of parent-adolescent
      agreement vary among societies for different kinds of problems? (c) How well do
      parents and adolescents in different societies agree on problem item ratings? (d)
      How much do parent-adolescent dyads within each society vary in agreement on item
      ratings? (e) How well do parent-adolescent dyads within each society agree on the
      adolescent's deviance status? We used five methods to test cross-informant
      agreement for ratings obtained from 27,861 adolescents ages 11 to 18 and their
      parents. Youth Self-Report (YSR) mean scores were significantly higher than Child
      Behavior Checklist (CBCL) mean scores for all problem scales in almost all
      societies, but the magnitude of the YSR-CBCL discrepancy varied across societies.
      Cross-informant correlations for problem scale scores varied more across
      societies than across types of problems. Across societies, parents and
      adolescents tended to rate the same items as low, medium, or high, but within
      dyad parent-adolescent item agreement varied widely in every society. In all
      societies, both parental noncorroboration of self-reported deviance and
      adolescent noncorroboration of parent-reported deviance were common. Results
      indicated many multicultural consistencies but also some important differences in
      parent-adolescent cross-informant agreement. Our findings provide valuable
      normative baselines against which to compare multicultural findings for clinical
      samples.

PMID- 23009026
TI  - Tetraoctylphosphonium tetrakis(pentafluorophenyl)borate room temperature ionic
      liquid toward enhanced physicochemical properties for electrochemistry.
AB  - Presented herein is the facile preparation of a new room temperature ionic liquid
      (RTIL), tetraoctylphosphonium tetrakis(pentafluorophenyl)borate (P(8888)TB).
      Subsequently, its physicochemical properties such as density, viscosity, and
      conductivity were characterized relative to temperature, demonstrating values of
      1.22 g.cm(-3), 727 mPa.s, and 180 MUS.cm(-1), respectively, at 60  degrees C. The
      electrochemistry of P(8888)TB was also investigated using cyclic voltammetry at a
      Pt-disk ultramicroelectrode and at a microinterface between water and the RTIL;
      this analysis revealed a wide metal-electrolyte potential window, ~3.5 V, and a
      large liquid|liquid polarizable potential window, ~0.9 V, at a temperature of 60 
      degrees C. Additionally, electron transfer (ET) reactions at a metal
      electrode|RTIL interface along with ion transfer (IT) reactions at the
      water|P(8888)TB interface were examined; the kinetics of these reactions were
      explored using finite element analysis. Increased ET and IT kinetics combined
      with enhancements of physicochemical properties versus RTILs we made previously
      seemingly suggest modest improvements. However, taken as a whole, they
      demonstrate significant progress toward a hydrophobic RTIL that can be used in
      conventional electrochemistry and biphasic metal ion extractions.

PMID- 23009027
TI  - Ruthenium(II) thiacrown complexes incorporating noninnocent redox active ligands:
      synthesis, electrochemical properties, and theoretical studies.
AB  - The synthesis and characterization of a series of nine new complexes
      incorporating [Ru(II)Cl([n]aneS(3))] (n = 12,14, 16) metal centers coordinated to
      redox active catechol ligands is reported. The solid-state structure of one of
      these complexes has been determined by X-ray crystallography. The redox
      properties of these complexes have been probed experimentally through absorption
      spectroscopy, cyclic voltammetry, and spectroelectrochemistry, as well as
      computationally through density functional theory calculations. These studies
      reveal that, whereas the tetrachlorocatechol-based complexes are isolated with
      the dioxolene unit in the catechol form, the rest of the complexes are isolated
      in the semiquinone oxidation state. It was also found that the Ru(III/II)-based
      couple for the complexes is dependent on the nature of the thiacrown ligand
      coordinated to the metal center. A combination of optical and theoretical studies
      revealed that the absorption spectra of the complexes contain contributions from
      a variety of charge transfer processes; in the case of the tetrachlorocatechol
      complexes these transitions include catechol-to-thiacrown ligand-to-ligand charge
      transfer.

PMID- 23009028
TI  - Understanding and optimizing the dual excipient functionality of sodium lauryl
      sulfate in tablet formulation of poorly water soluble drug: wetting and
      lubrication.
AB  - PURPOSE: To evaluate and optimize sodium lauryl sulfate (SLS) and magnesium
      stearate (Mg.St) levels, with respect to dissolution and compaction, in a high
      dose, poorly soluble drug tablet formulation. METHODS: A model poorly soluble
      drug was formulated using high shear aqueous granulation. A D-optimal design was
      used to evaluate and model the effect of granulation conditions, size of milling
      screen, SLS and Mg.St levels on tablet compaction and ejection. The compaction
      profiles were generated using a Presster((c)) compaction simulator. Dissolution
      of the kernels was performed using a USP dissolution apparatus II and intrinsic
      dissolution was determined using a stationary disk system. RESULTS: Unlike
      kernels dissolution which failed to discriminate between tablets prepared with
      various SLS contents, the intrinsic dissolution rate showed that a SLS level of
      0.57% was sufficient to achieve the required release profile while having minimal
      effect on compaction. The formulation factors that affect tablet compaction and
      ejection were identified and satisfactorily modeled. The design space of best
      factor setting to achieve optimal compaction and ejection properties was
      successfully constructed by RSM analysis. CONCLUSIONS: A systematic study design
      helped identify the critical factors and provided means to optimize the
      functionality of key excipient to design robust drug product.

PMID- 23009029
TI  - Negligible environmental sensitivity of graphene in a hexagonal boron
      nitride/graphene/h-BN sandwich structure.
AB  - Using Raman spectroscopy, we study the environmental sensitivity of mechanically
      exfoliated and electrically floating single-layer graphene transferred onto a
      hexagonal boron nitride (h-BN) substrate, in comparison with graphene deposited
      on a SiO(2) substrate. In order to understand and isolate the substrate effect on
      graphene electrical properties, we model and correct for Raman optical
      interference in the substrates. As-deposited and unannealed graphene shows a
      large I(2D)/I(G) ratio on both substrates, indicating extremely high quality,
      close to that of graphene suspended in vacuum. Thermal annealing strongly
      activates subsequent environmental sensitivity on the SiO(2) substrate; such
      activation is reduced but not eliminated on the h-BN substrate. In contrast, in a
      h-BN/graphene/h-BN sandwich structure, with graphene protected on both sides,
      graphene remains pristine despite thermal processing. Raman data provide a deeper
      understanding of the previously observed improved graphene electrical
      conductivity on h-BN substrates. In the sandwich structure, the graphene 2D Raman
      feature has a higher frequency and narrower line width than in pristine suspended
      graphene, implying that the local h-BN environment modestly yet measurably
      changes graphene electron and phonon dispersions.

PMID- 23009030
TI  - Effects of care pathways on the in-hospital treatment of heart failure: a
      systematic review.
AB  - BACKGROUND: Care pathways have become a popular tool to enhance the quality of
      care by improving patient outcomes, promoting patient safety, increasing patient
      satisfaction, and optimizing the use of resources. We performed a disease
      specific systematic review to determine how care pathways in the hospital
      treatment of heart failure affect in-hospital mortality, length of in-hospital
      stay, readmission rate and hospitalisation cost when compared with standard care.
      METHODS: Medline, Cinahl, Embase and the Cochrane Central Register of Controlled
      Trials were searched from 1985 to 2010. Each study was assessed independently by
      two reviewers. Methodological quality of the included studies was assed using the
      Jadad methodological approach for randomised controlled trials, controlled
      clinical trials and the New Castle Ottawa Scale for case-control studies, cohort
      studies and time interrupted series. RESULTS: Seven studies met the study
      inclusion criteria and were included in the systematic review with a total sample
      of 3,690 patients. The combined overall results showed that care pathways have a
      significant positive effect on mortality and readmission rate. A shorter length
      of hospital stay was also observed compared with the standard care group. No
      significant difference was found in the hospitalisation costs. More positive
      results were observed in controlled trials compared to randomized controlled
      trials. CONCLUSION: By combining all possible results, it can be concluded that
      care pathways for treatment of heart failure decrease mortality rates and length
      of hospital stay, but no statistically significant difference was observed in the
      readmission rates and hospitalisation costs. However, one should be cautious with
      overall conclusions: what works for one organization may not work for another
      because of the subtle differences in processes and bottlenecks.

PMID- 23009031
TI  - Tamm-Horsfall protein facilitates catheter associated urinary tract infection.
AB  - BACKGROUND: Urinary catheters are associated, commonly with bacteriuria and
      frequently with urinary tract infection. Tamm-Horsfall Protein (THP) is urine's
      most abundant protein and is known to bind to uropathogenic bacteria. The role of
      THP in the pathogenesis of catheter associated urinary tract infection (CAUTI) is
      not clear. We examined the role of THP in facilitating bacterial binding to
      urinary catheters in vivo and in vitro. FINDINGS: Twenty one urinary catheters
      were obtained from 20 hospitalized patients. THP was eluted from the catheter
      surface and catheter segments were cultured. Additional studies were performed in
      vitro on unused silicone and latex catheters to determine the binding of THP, and
      the effect of THP on the binding of Escherichia coli (E. coli) and Pseudomonas
      aeruginosa (P. aeruginosa), to the catheter surface.On catheters obtained from
      patients, the THP deposition was significantly more on culture positive catheters
      than on culture negative catheters. In the in vitro studies, THP bound to both
      silicone and latex catheters, and THP enhanced the adherence of E. coli and P.
      aeruginosa to both types of catheters. CONCLUSION: THP binds to urinary catheters
      and facilitates the binding of uropathogenic bacteria to catheters.

PMID- 23009032
TI  - Formulation and optimization of spray-dried amlodipine solid dispersion for
      enhanced oral absorption.
AB  - OBJECTIVE: To enhance the oral absorption of photosensitive amlodipine free base,
      which exhibits a slow dissolution rate and low permeability characteristics, an
      amorphous solid dispersion system was formulated and characterized. MATERIAL AND
      METHODS: The solid dispersion was prepared by dispersing the amlodipine free base
      in excess dextrin (1:10 by weight) using a spray-drying technique in the presence
      of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin
      based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of
      formulation, characterization and in vivo absorption study, as well as the spray
      drying process was also optimized. RESULTS AND DISCUSSION: The Amlo-SD particles
      were spherical with a smooth surface and an average particle size of 12.9 MUm.
      Amlodipine was dispersed in an amorphous state and its content remained uniform
      in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at
      room temperature for 6 months and the photostability was considerably improved.
      The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2
      and 6.8. Amlo-SD produced significantly higher plasma concentrations of
      amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided
      2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be
      attributed to a permeability enhancement effect by SLS. CONCLUSION: The Amlo-SD
      with SLS system is a potential formulation option for amlodipine.

PMID- 23009033
TI  - Anisotropic chemical pressure effects in single-component molecular metals based
      on radical dithiolene and diselenolene gold complexes.
AB  - On the basis of the reported radical neutral complex [Au(Et-thiazdt)(2)] (Et
      thiazdt = N-ethyl-1,3-thiazoline-2-thione-4,5-dithiolate), a series of single
      component conductors derived from [Au(Et-thiazdt)(2)], also noted as
      [AuS(4)(?S)(2)], has been developed, by replacing the outer sulfur atoms of the
      thiazoline-2-thione rings by oxygen atoms and/or by replacing the coordinating
      sulfur atoms by selenium atoms toward the corresponding diselenolene complexes.
      Comparison of the X-ray crystal structures and transport properties of the four
      isostructural complexes, noted as [AuS(4)(?S)(2)], [AuS(4)(?O)(2)],
      [AuSe(4)(?S)(2)], and [AuSe(4)(?O)(2)], shows that the oxygen substitution on the
      outer thiazoline ring actually decreases the conductivity by a factor of 100,
      despite a contracted unit cell volume reflecting a positive chemical pressure
      effect. On the other hand, the S/Se substitution increases the conductivity by a
      factor of 100, and the pressure needed to transform these semiconductors into the
      metallic state is shifted from 13 kbar in [AuS(4)(?S)(2)] to only ~6 kbar in
      [AuSe(4)(?S)(2)]. Analysis of unit cell evolutions and ab initio band structure
      calculations demonstrates the strongly anisotropic nature of this chemical
      pressure effect and provides an explanation for the observed changes in
      conductivity. The greater sensitivity of these neutral single-component
      conductors to external pressure, as compared with "classical" radical salts, is
      also highlighted.

PMID- 23009034
TI  - A comparison of fingerprint sweat corrosion of different alloys of brass.
AB  - Fingerprint sweat from 40 donors was deposited onto samples of five alpha and
      alpha + beta phase brasses, comprising five alloys with different copper and zinc
      concentrations, two of which also had the addition of small concentrations of
      lead. Visual grading of the visibility of the corrosion revealed that brasses
      with the least amount of zinc produced the most visible and fully formed
      fingerprints from the most donors. Consideration of previously reported
      mechanisms for the corrosion of brass suggests red copper (I) oxide as a likely
      corrosion product for low zinc brasses, and a consideration of the color,
      composition, and solubility of fingerprint sweat corrosion products suggests that
      copper (I) oxide produces good contrast and visibility with the brass substrate.
      Scanning electron microscope images of the corrosion of all five alloys confirmed
      the enhanced contrast between corroded and uncorroded areas for low zinc alloys.

PMID- 23009035
TI  - Novel use of intrathecal baclofen drug delivery system for periodic focal
      dystonia in a teenager.
AB  - INTRODUCTION:  Focal dystonia, often affecting part of a limb, is a manifestation
      of complex regional pain syndrome (CRPS). This can be difficult to diagnose and
      treat. Furthermore, there may be significant latency between the onset of
      dystonia after the diagnosis of CRPS. We present the case of a 15-year-old girl
      with periodic focal dystonia who has been successfully treated with an
      intrathecal baclofen pump. MATERIALS AND METHODS:  The patient had sustained a
      minor ankle fracture four years prior to presentation. Despite radiologic
      evidence of adequate bony union, the patient continued to complain of spasms and
      pain in her left foot leading to dystonic posturing of the foot. Multiple
      therapies including subcutaneous morphine infusion, ankle splinting,
      physiotherapy, and local botulinum injections had not provided adequate relief.
      Intrathecal baclofen on three separate occasions resulted in successful temporary
      resolution of the dystonia. A placebo double-blinded injection of intrathecal
      saline at a separate setting however did not resolve the dystonia. RESULTS:  We
      then proceeded with permanent delivery of baclofen by implantation of an
      intrathecal drug delivery pump, which resulted in resolution of the dystonia. The
      patient also was able to receive bolus doses of intrathecal baclofen. The patient
      is now able to partake in sporting and dancing activities. A detailed history of
      the patient, along with the difficulties in diagnosis and management, is
      presented. CONCLUSION:  Intrathecal baclofen therapy can be effective in the
      management of focal dystonia after rigorous preoperative testing and counseling
      of adolescents with CRPS.

PMID- 23009036
TI  - Polymorphisms of the CD14 genes are associated with susceptibility to alcoholic
      liver disease in Greek patients.
AB  - BACKGROUND: The incidence and severity of alcoholic liver disease (ALD) in
      chronic drinkers has been found to correlate with some environmental factors and
      especially with the dose of alcohol consumption, but it is obvious that other
      parameters clearly contribute to individual alcohol susceptibility. Chronic
      ethanol exposure leads to continuous endotoxin-mediated Toll-like receptor-4 (TLR
      4) and CD14 activation and subsequent cytokine release resulting in chronic
      inflammation with continued hepatocellular damage. Therefore, genetic studies of
      polymorphism in TLR-4 and CD14 genes seem to be appropriate in determining
      genetic susceptibility to ALD. Our aim is to evaluate in a series of Greek
      drinkers, the possible association of polymorphisms in the TLR-4 and CD14 genes
      with ALD. METHODS: In 96 patients with ALD polymorphism of TLR-4 and CD14 genes
      were studied compared with 104 patients with cirrhosis of other etiology, 100
      healthy subjects, and 50 patients with a history of alcohol abuse but without
      liver disease. RESULTS: No association between ALD and the presence of the
      Asp299Gly and Thr399Ile polymorphisms in the TLR-4 gene could be documented in
      our patients. Regarding the CD14 -159 (C/T) genotypes, TT genotype and T allele
      were found to be overrepresented in alcoholic patients compared with patients
      with nonalcohol-induced liver disease and healthy controls. On the other side,
      when compared patients with ALD and patients with alcohol abuse and no liver
      disease, TT genotype was found to be significantly less frequent. There is no
      statistically significant association with the presence of the T allele and the
      severity of ALD, suggesting that CD14 polymorphism does not influence disease
      severity in advanced stages of the disease. CONCLUSIONS: In our series in Greek
      patients with alcohol abuse and alcoholic cirrhosis, a significant negative
      association with the CD14 endotoxin receptor gene polymorphism (TT genotype) but
      not with the TLR-4 gene polymorphism was documented.

PMID- 23009038
TI  - Eliminating the dreaded "so what?".

PMID- 23009039
TI  - An integrative review of the literature about the transition of pediatric
      patients with intestinal failure from hospital to home.
AB  - PURPOSE: Children with intestinal failure (IF) have complex needs that pose many
      challenges while in the hospital and upon transition to home. The purpose of this
      review was to identify factors associated with the complexity of transitional
      care in this population of children, as well as to explore frameworks for
      providing care for transition to home. DESIGN AND METHOD: Eleven publications,
      including research and clinical practice articles, were identified for an
      integrative review. RESULTS: Four themes emerged regarding IF and transition:
      complex healthcare needs, planning for and beginning transition, identification
      of family requirements, and frameworks for providing transitional care. PRACTICE
      IMPLICATIONS: Nurses working with families of children with IF can facilitate
      successful transition into the home by planning in advance and using a framework
      that addresses the needs of the patient and family.

PMID- 23009037
TI  - Full correction and Undercorrection of Myopia Evaluation Trial: design and
      baseline data of a randomized, controlled, double-blind trial.
AB  - BACKGROUND: To determine the difference in the rate of myopic progression between
      children wearing single vision lenses with undercorrection of +0.50 D and
      children whose myopia is fully corrected, and to explore the factors that may
      influence the process. DESIGN: Randomized, controlled, double-blind trial.
      PARTICIPANTS: Two hundred children aged 7-15 years with low-to-moderate myopia (
      1.5 D to -6.0 D), astigmatism <-1.5 D and anisometropia <1.0 D. METHODS: The
      children were randomly allocated to wear single vision lenses with full
      correction or undercorrection by +0.50 D. Ocular examinations and questionnaire
      surveys for myopia-related factors will be performed every 6 months. MAIN OUTCOME
      MEASURES: Cycloplegic autorefraction and axial length. RESULTS: Of 200 children,
      100 (50%) were girls, 41 (21%) esophoric and 82 (42%) exophoric at near. The
      characteristics of gender, age, age of myopia onset, phoria, eye dominance,
      parental myopia, refractive error, axial length, corneal curvature, mean time
      spent in near work and outdoor activities between the two groups were not
      significantly different. The accommodative responses at 33 cm, the accommodative
      demands and lags at infinity were significantly different in the two groups as
      they were measured with full correction in one group and undercorrection in the
      other. CONCLUSION: Full correction and Undercorrection of Myopia Evaluation Trial
      is a clinical trial designed to determine the effectiveness of undercorrection of
      myopia by +0.5 D on myopic progression in a population of school-aged children
      known to be susceptible to myopia and to identify the factors influencing the
      process.

PMID- 23009040
TI  - 17-year outcome of preterm infants with diverse neonatal morbidities: part 2,
      impact on activities and participation.
AB  - PURPOSE: To examine functioning and participation in a diverse U.S. sample of 180
      infants at age 17 years. DESIGN AND METHODS: The World Health Organization
      International Classification of Functioning, Disability and Health model framed
      functioning and participation domains and contextual factors. Assessment included
      cognition, executive functioning, academic achievement, personal functioning,
      community participation, and social involvement. RESULTS: Socioeconomic status,
      not prematurity, impacted cognitive and academic outcomes. Across neonatal
      morbidities, male gender and social disadvantage are key determinants of
      cognitive, academic, and social functioning. PRACTICE IMPLICATIONS: Interventions
      addressing academic and social-behavioral competencies in early school years may
      potentially optimize long-term preterm outcomes.

PMID- 23009041
TI  - Gender differences in associations between parental problem drinking and early
      adolescents' internet addiction.
AB  - PURPOSE: The purpose was to examine gender differences between parental problem
      drinking (PPD) and early adolescents' Internet addiction (IA). DESIGN AND
      METHODS: This was a cross-sectional, correlational design with 519 (266 boys and
      253 girls) early adolescents. RESULTS: PPD had a significant direct effect on IA
      in boys but not in girls. Significant indirect effects of PPD on IA were
      evidenced via anxiety-depression and aggression for boys and via family function
      and aggression for girls. PRACTICE IMPLICATIONS: Findings suggest that tailored
      interventions for the prevention of IA should consider gender.

PMID- 23009042
TI  - Nutritional status among pediatric cancer patients: a comparison between
      hematological malignancies and solid tumors.
AB  - PURPOSE: This study aimed to compare the nutritional status of pediatric patients
      with hematological malignancies and solid tumors. DESIGN AND METHODS: A total of
      74 pediatric cancer patients were assessed for anthropometric status, biochemical
      profiles, and dietary intake. RESULTS: The prevalence of undernutrition was
      higher among patients with solid tumors as reflected in their lower dietary
      intakes of energy and nutrients compared with patients with hematological
      malignancies. PRACTICE IMPLICATION: Adequate dietary intake is important for
      pediatric cancer patients, but nurses need to pay more attention to the diets of
      patients with solid tumors as compared with those with hematological
      malignancies.

PMID- 23009043
TI  - A parent-directed portion education intervention for young children: Be Beary
      Healthy.
AB  - PURPOSE: This pilot study aimed to determine the effects of an intervention on
      nutrition knowledge, food parents serve, and children's dietary intake. DESIGN
      AND METHODS: A single-group pre-/posttest design was used with 45 mothers and
      their 4- to 6-year-old children. After pretesting, parents received child
      nutrition information and portion-related activities. RESULTS: Paired samples t
      tests revealed that from pre- to posttest the average calories mothers served and
      the average calories children ate significantly decreased (medium effect size).
      Medium effects also were recognized from pre- to posttest for the carbohydrates
      served and carbohydrates consumed. No significant change was found in parents'
      nutrition knowledge. PRACTICE IMPLICATIONS: Interventions focusing on skill
      building rather than on increasing knowledge may more effectively lead to changed
      child intake.

PMID- 23009044
TI  - Expectations associated with the use of music in neonatal intensive care: a
      survey from the viewpoint of parents.
AB  - PURPOSE: The purpose of this study was to describe parents' expectations
      concerning the use of music in a neonatal intensive care unit (NICU) and to
      reveal any related background factors. DESIGN AND METHODS: A cross-sectional,
      descriptive, and correlational design guided a survey of 197 parents from five
      NICUs in Finland. RESULTS: Most parents agreed that the preferred music could
      have positive effects on the infants, staff, and parents in the NICU. PRACTICE
      IMPLICATIONS: When nurses consider making use of music in the NICU, it is also
      important to take into account the parents' viewpoints.

PMID- 23009045
TI  - Pediatric skin care: what do nurses really know?
AB  - PURPOSE: The purpose of this study was to explore pediatric nurses' knowledge of
      pressure ulcer prevention, investigate their beliefs and practices, and identify
      the barriers and facilitators to providing evidence-based pressure ulcer
      preventive practices. DESIGN AND METHODS: An exploratory, descriptive, and cross
      sectional survey was taken of registered nurses in a freestanding children's
      hospital. RESULTS: Nurses have adequate knowledge of general pressure ulcer
      prevention; however, they struggle with individualization. Further, analysis
      revealed that nursing knowledge did not always correlate with nursing practice.
      PRACTICE IMPLICATIONS: Nurses require education on individualized interventions
      and access to user-friendly, interactive, and comprehensive resources, including
      unit-based champions and order sets.

PMID- 23009046
TI  - Recognizing the healthcare needs of Ethiopia's children.

PMID- 23009048
TI  - Experienced workers exhibit distinct torso kinematics/kinetics and patterns of
      task dependency during repetitive lifts and lowers.
AB  - Individual differences in work methods may be related to the risk of injury
      during manual material handling tasks, yet existing evidence comparing
      experienced workers and novices is mixed. This study assessed torso kinematics
      and kinetics among six experienced workers and six novices during repetitive
      lifts/lowers under different task configurations (symmetric vs. asymmetric and
      lift vs. lower). Several important potential confounding effects were controlled.
      Peak kinematic and kinetic measures were typically higher among experienced
      workers and suggestive of exposure to higher levels of low back injury risk,
      though overall exposure levels were moderate. Work methods used by experienced
      workers were modified between task conditions, whereas novice behaviours were
      more consistent. Control of torso kinematics/kinetics may thus not be a primary
      factor in determining experienced worker's work methods, and future investigation
      is needed to establish if, or under what conditions, these methods are protective
      and/or should be the basis for interventions including training. PRACTITIONER
      SUMMARY: Whether lifting experience reduces low back injury risk is unclear from
      earlier findings. Results from a controlled experiment suggest that lifting
      experience may not be associated consistently with reduced physical demands or
      injury risk. Further investigation is needed to assess the utility of training
      based on the methods of experienced workers.

PMID- 23009047
TI  - Fire ignition during laser surgery in pet rodents.
AB  - BACKGROUND: Laser surgery is an attractive alternative to other means of section
      device in terms of tissue inflammation and interaction, which has been
      extensively used in human and veterinary medicine. Although accidental ignition
      during laser surgeries is sporadically reported in human medical literature, to
      the authors' knowledge this is the first report regarding laser-dependent fire
      ignition during surgery in veterinary medicine. CASE PRESENTATION: Two rodents, a
      13-month old, 27-gram, male pet mouse (Mus musculus) and a 1-year old, female
      Russian hamster (Phodopus sungorus), underwent surgical removal of masses with
      diode laser. During the surgical procedures fires ignited from the face masks.
      The mouse presented severe burns on the head and both forelimbs, it was
      hospitalized and approximately 2 months after surgery burns were resolved. The
      hamster presented severe burns on the face and the proximal regions of the body.
      At 72 hours from the accident the hamster was euthanized. CONCLUSION: The present
      report suggests that fire ignition is a potential life-threatening complication
      of laser surgery in non-intubated rodents maintained under volatile anesthesia.
      High oxygen concentrations, the presence of combustible, and the narrowness of
      the surgical field with the face mask during laser surgery on rodents are risk
      factors for fire ignition.

PMID- 23009049
TI  - Sports injuries among adolescents: incidence, causes and consequences.
AB  - AIM: The purpose of this study was to evaluate the 1-year incidence, location,
      type, mechanism and severity of sports injuries for adolescents in Germany.
      METHODS: Data were from the 'German Health Interview and Examination Survey for
      Children and Adolescents', a nationwide study of n = 17 641 children and
      adolescents. Analyses were based on a weighted total sample size of n(w) = 7451
      adolescents between 11 and 17 years of age, 51% of them boys. RESULTS: A total of
      577 adolescents (8%) reported having experienced a sports injury during the past
      year. Collisions and falls were reported as being the most important causes. The
      most frequent diagnoses were contusions, dislocations, strains and sprains (60%),
      followed by fractures (26%). Most injuries (88%) were treated on an outpatient
      basis with only 12% resulting in hospitalisation. Gender-specific analyses showed
      that 9% of the boys and 7% of the girls suffered from a sports injury during the
      past year. After adjusting for the level of physical activity, these gender
      differences disappeared (OR(girls) 0.94; 95% confidence intervals: 0.74-1.18).
      Excluding injuries incurred from falls while horse riding, there were no gender
      differences in the mechanism of injury. Among boys, 30% of all injuries were
      fractures, among girls 20% (P < 0.05). Apart from fractures, no further
      differences between the sexes in the range of diagnoses were identified.
      CONCLUSIONS: Although these results suggest that the risk of sports injuries does
      not differ significantly based on adolescents' gender, the incidence rate of
      adolescent sports injuries within Germany is relatively high.

PMID- 23009050
TI  - Measurement and scaling of hydrodynamic interactions in the presence of draining
      channels.
AB  - Central to the adhesion and locomotion of tree frogs are their structured toe
      pads, which consist of an array of 10 MUm hexagonal epithelial cells separated by
      interconnected channels that are 1 MUm wide and 10 MUm deep. It has been proposed
      that the channels facilitate the drainage of excess fluid trapped between the toe
      pads and the contacting surface, and thus reduce the hydrodynamic repulsion
      during approach. We performed direct force measurement of the normal hydrodynamic
      interactions during the drainage of fluid from the gap between a structured and a
      smooth surface using surface force apparatus. The structured surface consisted of
      a hexagonal array of cylindrical posts to represent the network of interconnected
      channels. The measured hydrodynamic drainage forces agree with the predictions
      from Reynolds' theory for smooth surfaces at large separations. Deviations from
      theory, characterized by a reduction in the hydrodynamic repulsion, are observed
      below some critical separation (h(c)), which is independent of drive velocity. We
      employ a scaling analysis to establish the relationship between structural
      features (channel depth, width, and post diameter) and the critical separation
      for the onset of deviations. We find agreement between our experiments and the
      scaling analysis, which allows us to estimate a characteristic length scale that
      corresponds to the transition from the fluid being radially squeezed out of the
      nominal contact area to being squeezed out through the network of interconnected
      channels.

PMID- 23009051
TI  - Optical properties of silicon nanowire arrays formed by metal-assisted chemical
      etching: evidences for light localization effect.
AB  - We study the structure and optical properties of arrays of silicon nanowires
      (SiNWs) with a mean diameter of approximately 100 nm and length of about 1-25 MUm
      formed on crystalline silicon (c-Si) substrates by using metal-assisted chemical
      etching in hydrofluoric acid solutions. In the middle infrared spectral region,
      the reflectance and transmittance of the formed SiNW arrays can be described in
      the framework of an effective medium with the effective refractive index of about
      1.3 (porosity, approximately 75%), while a strong light scattering for wavelength
      of 0.3 / 1 MUm results in a decrease of the total reflectance of 1%-5%, which
      cannot be described in the effective medium approximation. The Raman scattering
      intensity under excitation at approximately 1 MUm increases strongly in the
      sample with SiNWs in comparison with that in c-Si substrate. This effect is
      related to an increase of the light-matter interaction time due to the strong
      scattering of the excitation light in SiNW array. The prepared SiNWs are
      discussed as a kind of 'black silicon', which can be formed in a large scale and
      can be used for photonic applications as well as in molecular sensing.

PMID- 23009052
TI  - Linking management effectiveness indicators to observed effects of protected
      areas on fire occurrence in the Amazon rainforest.
AB  - Management-effectiveness scores are used widely by donors and implementers of
      conservation projects to prioritize, track, and evaluate investments in protected
      areas. However, there is little evidence that these scores actually reflect the
      capacity of protected areas to deliver conservation outcomes. We examined the
      relation between indicators of management effectiveness in protected areas and
      the effectiveness of protected areas in reducing fire occurrence in the Amazon
      rainforest. We used data collected with the Management Effectiveness Tracking
      Tool (METT) scorecard, adopted by some of the world's largest conservation
      organizations to track management characteristics believed to be crucial for
      protected-area effectiveness. We used the occurrence of forest fires from 2000
      through 2010 as a measure of the effect of protected areas on undesired land
      cover change in the Amazon basin. We used matching to compare the estimated
      effect of protected areas with low versus high METT scores on fire occurrence. We
      also estimated effects of individual protected areas on fire occurrence and
      explored the relation between these effects and METT scores. The relations
      between METT scores and effects of protected areas on fire occurrence were weak.
      Protected areas with higher METT scores in 2005 did not seem to have performed
      better than protected areas with lower METT scores at reducing fire occurrence
      over the last 10 years. Further research into the relations between management
      effectiveness indicators and conservation outcomes in protected areas seems
      necessary, and our results show that the careful application of matching methods
      can be a suitable method for that purpose.

PMID- 23009054
TI  - Behavioral health providers' perspectives of delivering behavioral health
      services in primary care: a qualitative analysis.
AB  - BACKGROUND: Co-located, collaborative care (CCC) is one component of VA's model
      of Integrated Primary Care that embeds behavioral health providers (BHPs) into
      primary care clinics to treat commonly occurring mental health concerns among
      Veterans. Key features of the CCC model include time-limited, brief treatments
      (up to 6 encounters of 30 minutes each) and emphasis on multi-dimensional
      functional assessment. Although CCC is a mandated model of care, the barriers and
      facilitators to implementing this approach as identified from the perspective of
      BHPs have not been previously identified. METHODS: This secondary data analysis
      used interview data captured as part of a quality improvement project in 2008.
      Fourteen BHPs (48% of providers in a regional VA network) agreed to participate
      in a 30-minute, semi-structured phone interview. The interview included questions
      about their perceived role as a CCC provider, depiction of usual practice styles
      and behaviors, and perceptions of typical barriers and facilitators to providing
      behavioral healthcare to Veterans in CCC. Interviews were transcribed verbatim
      into a text database and analyzed using grounded theory. RESULTS: Six main
      categories emerged from the analysis: (a) Working in the VA Context, (b) Managing
      Access to Care on the Front Line, (c) Assessing a Care Trajectory, (d) Developing
      a Local Integrated Model, (e) Working in Collaborative Teams, and (f) Being a
      Behavioral Health Generalist. These categories pointed to system, clinic, and
      provider level factors that impacted BHP's role and ability to implement CCC.
      Across categories, participants identified ways in which they provided Veteran
      centered care within variable environments. CONCLUSIONS: This study provided a
      contextualized account of the experiences of BHP's in CCC. Results suggest that
      these providers play a multifaceted role in delivering clinical services to
      Veterans while also acting as an interdependent component of the larger VA
      behavioral health and primary care systems. Based on the inherent challenges of
      enacting this role, BHPs in CCC may benefit from additional implementation
      support in their effort to promote health care integration and to increase access
      to patient-centered care in their local clinics.

PMID- 23009053
TI  - A systematic review of symptom assessment scales in children with cancer.
AB  - BACKGROUND: The objective was to describe symptom assessment scales that have
      been used in children with cancer. METHODS: We conducted electronic searches of
      OVID Medline and EMBASE in order to identify all symptom assessment scales that
      have been used in pediatric cancer. Two reviewers abstracted information from
      each identified study. Data collected included study demographics and information
      related to the instrument and children enrolled. We also collected information
      about the purpose of instrument administration and whether treatment was altered
      as a result of this information. RESULTS: Fourteen studies were identified which
      evaluated eight different symptom assessment scales. Eight studies used child
      self-report and all studies included children on active treatment for cancer
      although 4 studies also included children following completion of treatment. The
      most common purpose of instrument administration was to measure the prevalence of
      symptom burden (n = 8). None of the 14 studies used the scale to screen for
      symptoms and none changed patient management on the basis of identified symptoms.
      CONCLUSIONS: We failed to identify any symptom assessment scales that were used
      as a symptom screening tool. There is a need to develop such a tool for use in
      children with cancer.

PMID- 23009055
TI  - Working with previously anonymous gamete donors and donor-conceived adults:
      recent practice experiences of running the DNA-based voluntary information
      exchange and contact register, UK DonorLink.
AB  - This article describes recent practice experiences with donor conceived adults,
      donors, non-donor-conceived adult children of donors using the voluntary DNA
      based register, UK DonorLink. It highlights additional complexities faced when
      using DNA rather than paper records for searching, in particular from the risk of
      false positives, low chances of success and potential inclusion of biological
      parents' DNA. Professionals' experiences in supporting those being "linked"
      suggest challenges as well as rewards. Registration carries the potential to be
      therapeutic for donor-conceived adults and donors and to enhance their political
      awareness regardless of links being made. Registrants value both peer and
      professional support, providing the latter can respond flexibly and be delivered
      by staff experienced in intermediary work. Given that the majority of those
      affected by donor conception internationally come from anonymous donation
      systems, these findings are highly pertinent and argue the need for political and
      moral debate about such service provision.

PMID- 23009056
TI  - Validation of alternative indicators of social support in perinatal outcomes
      research using quality of the partner relationship.
AB  - AIM: To test alternatives to the current research and clinical practice of
      assuming that married or partnered status is a proxy for positive social support.
      BACKGROUND: Having a partner is assumed to relate to better health status via the
      intermediary process of social support. However, women's health research
      indicates that having a partner is not always associated with positive social
      support. DESIGN: An exploratory post hoc analysis focused on posttraumatic stress
      and childbearing was conducted using a large perinatal database from 2005-2009.
      METHODS: To operationalize partner relationship, four variables were analysed:
      partner ('yes' or 'no'), intimate partner violence ('yes' or 'no'), the
      combination of those two factors, and the woman's appraisal of the quality of her
      partner relationship via a single item. Construct validity of these four
      alternative variables was assessed in relation to appraisal of the partner's
      social support in labour and the postpartum using linear regression standardized
      betas and adjusted R-squares. Predictive validity was assessed using unadjusted
      and adjusted linear regression modelling. RESULTS: Four groups were compared.
      Married, abused women differed most from married, not abused women in relation to
      the social support, and depression outcomes used for validity checks. The
      variable representing the women's appraisals of their partner relationships
      accounts for the most variance in predicting depression scores. CONCLUSIONS: Our
      results support the validity of operationalizing the impact of the partner
      relationship on outcomes using a combination of partnered status and abuse status
      or using a subjective rating of quality of the partner relationship.

PMID- 23009057
TI  - Importance of boundary on the electrophoresis of a soft cylindrical particle.
AB  - We modeled the electrophoresis of a soft cylindrical particle comprising a rigid
      core and a polyelectrolyte layer along the axis of a long, cylindrical pore, and
      the applicability of the model proposed is verified by the experimental data
      available in the literature. Previous analysis is extended to the case where the
      effects of double-layer polarization (DLP) and electroosmotic flow (EOF) can be
      significant. We show that the interaction between the particle's double layer and
      the pore, the competition between the effective charge density and the local
      electric field strength, and the presence of EOF yield interesting and
      significant results. For example, if EOF is absent, the particle mobility as the
      bulk salt concentration varies depends highly on the amount of fixed charge of
      its polyelectrolyte layer: if that amount is small, the mobility decreases
      monotonically with increasing bulk salt concentration, and if that amount is
      large, then the mobility shows a local maximum. At a high bulk salt
      concentration, the longer the particle the larger is its mobility, that trend is
      reversed if it is low. That local minimum vanishes when the boundary effect is
      important. If the pore is positively charged, a positively charged particle can
      be driven to the direction opposite to that of the applied electric field. These
      provide necessary information for the design of electrophoresis devices.

PMID- 23009058
TI  - A protecting-group-free synthesis of Hagen's gland lactones.
AB  - A practical protecting group free synthesis of Hagen's gland lactones 1 and 2 is
      accomplished in four steps and 25.6 and 37.4% overall yields, respectively. The
      strategy relies on a one-pot conversion of D-glucono-delta-lactone to beta
      hydroxy-gamma-vinyl-gamma-lactone, cross-metathesis, and iodocyclization
      deiodinization as key steps.

PMID- 23009059
TI  - Separating metagenomic short reads into genomes via clustering.
AB  - BACKGROUND: The metagenomics approach allows the simultaneous sequencing of all
      genomes in an environmental sample. This results in high complexity datasets,
      where in addition to repeats and sequencing errors, the number of genomes and
      their abundance ratios are unknown. Recently developed next-generation sequencing
      (NGS) technologies significantly improve the sequencing efficiency and cost. On
      the other hand, they result in shorter reads, which makes the separation of reads
      from different species harder. Among the existing computational tools for
      metagenomic analysis, there are similarity-based methods that use reference
      databases to align reads and composition-based methods that use composition
      patterns (i.e., frequencies of short words or l-mers) to cluster reads.
      Similarity-based methods are unable to classify reads from unknown species
      without close references (which constitute the majority of reads). Since
      composition patterns are preserved only in significantly large fragments,
      composition-based tools cannot be used for very short reads, which becomes a
      significant limitation with the development of NGS. A recently proposed
      algorithm, AbundanceBin, introduced another method that bins reads based on
      predicted abundances of the genomes sequenced. However, it does not separate
      reads from genomes of similar abundance levels. RESULTS: In this work, we present
      a two-phase heuristic algorithm for separating short paired-end reads from
      different genomes in a metagenomic dataset. We use the observation that most of
      the l-mers belong to unique genomes when l is sufficiently large. The first phase
      of the algorithm results in clusters of l-mers each of which belongs to one
      genome. During the second phase, clusters are merged based on l-mer repeat
      information. These final clusters are used to assign reads. The algorithm could
      handle very short reads and sequencing errors. It is initially designed for
      genomes with similar abundance levels and then extended to handle arbitrary
      abundance ratios. The software can be download for free at
      http://www.cs.ucr.edu/~tanaseio/toss.htm. CONCLUSIONS: Our tests on a large
      number of simulated metagenomic datasets concerning species at various
      phylogenetic distances demonstrate that genomes can be separated if the number of
      common repeats is smaller than the number of genome-specific repeats. For such
      genomes, our method can separate NGS reads with a high precision and sensitivity.

PMID- 23009060
TI  - Changes in muscle activation following ankle strength training in children with
      spastic cerebral palsy: an electromyography feasibility case report.
AB  - ABSTRACT Children with cerebral palsy (CP) are likely to experience decreased
      participation in activities and less competence in activities of daily living.
      Studies of children with spastic CP have shown that strengthening programs
      produce positive results in strength, gait, and functional outcomes (measured by
      the Gross Motor Function Measure). No investigations have analyzed
      electromyography (EMG) activity before and after strength training to determine
      whether any changes occur in the GMFM.  This feasibility case report quantified
      dorsiflexor and plantarflexor muscle activation changes during performance of 3-5
      selected GMFM items following a plantarflexor strength training in two children
      with cerebral palsy. Increased plantarflexor strength and increased ability to
      selectively activate muscles were found. Little carryover to performance on GMFM
      items was observed. It is feasible to use EMG during performance on selected GMFM
      items to evaluate motor control changes following strength training in children
      with CP.

PMID- 23009061
TI  - Management algorithms for primary angle closure disease.
AB  - In contrast to primary open angle glaucoma, preventive interventions in primary
      angle closure disease (PACD) can sometimes be definitive. Data from randomized,
      controlled trials - and where this is not available - principles grounded in
      known biology, biological plausibility, logic, preferred practice and personal
      experience have been synthesized to develop explicit clinical algorithms for
      management of the spectrum of PACD. The mainstay of first-line intervention is
      usually a laser iridotomy: a commonly necessary but sometimes insufficient
      manoeuvre in PACD. The crucial stepwise considerations after iridotomy are:
      whether the angle is open or closed; whether the IOP can be medically controlled;
      the extent of PAS, and the presence of visually significant cataract. Indication
      for subsequent interventions--which may include iridoplasty, cataract surgery,
      trabeculectomy or phacotrabeulectomy--are herein based on an arbitrary threshold
      (180 degrees) for angle opening and extent of PAS following initial treatment.

PMID- 23009062
TI  - Long-term binge and escalating ethanol exposure causes necroinflammation and
      fibrosis in rat liver.
AB  - BACKGROUND: To investigate whether "binge" and escalating alcohol exposure in the
      rat influences the development of pathological liver injury. METHODS: Time
      courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative
      stress and nitrosative stress production, expression of hypoxia-inducible factor
      1 (HIF-1), cytokines, hepatic tissue necroinflammation, and fibrosis were
      assessed in rats during 16 weeks of daily alcohol gavage. RESULTS: In this model
      of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and
      inflammation as well as fibrosis were increased over the 16-week period. The
      levels of COX-2, oxidative stress, nitrosative stress, HIF-1, proinflammatory
      mediators (tumor necrosis factor-alpha, interleukin 1(beta)  [IL-1(beta) ], IL
      6), and procollagen-I were increased over the 16-week period. The content of IL
      10 in rat serum increased at the end of 4 and 8 weeks but decreased thereafter
      and was significantly decreased at 12 and 16 weeks. CONCLUSIONS: A rat model of
      alcoholic liver disease (ALD) with long-term binge and escalating ethanol
      exposure was developed. Our data support the hypothesis that enhanced eicosanoid
      production by COX, oxidative stress and nitrosative stress, HIF-1, and the
      imbalance between pro- and anti-inflammatory cytokines plays an important role in
      the pathogenesis of ALD.

PMID- 23009064
TI  - Adsorption of diblock polypeptides on polystyrene latex.
AB  - The adsorption of peptides at solid/liquid interfaces is affected by
      peptide/surface and peptide/peptide hydrophobic and electrostatic forces. Three
      diblock copolypeptides and two homopeptides were adsorbed on poly(styrene)
      nanospheres from water, water/methanol, and water/glycerol mixtures at different
      pH's to study both of these effects. Peptides with one hydrophilic (glutamic acid
      or lysine) and one nonpolar block (alanine) or with both hydrophilic blocks with
      opposite charges (glutamic acid and lysine) were chemically synthesized and used
      as adsorbates in this study. The amount adsorbed was determined, and dynamic
      light scattering (DLS) was used to measure the adsorbed layer thickness. It was
      found that peptide/surface and peptide/peptide electrostatic interactions
      dominate the adsorption process. Hydrophobic forces also play a role, but
      secondary to electrostatic forces. Positively charged blocks show high affinity
      for the surface, whereas negatively charged blocks were excluded from it.
      Poly(Lys) has the highest affinity by the surface, while (Glu)(14)-b-(Ala)(5) has
      the lowest. Adsorption of all peptides was inhibited by methanol and promoted by
      glycerol. The adsorption for (Lys)(5)-b-(Glu)(6) was extremely sensitive to pH,
      irrespective of cosolvent, whereas the thickness for (Lys)(30)-b-(Ala)(41) was
      sensitive to pH as well as cosolvent. Aggregation was observed in the presence of
      the nanosurfaces but not in the bulk peptides under some pH and solvent
      conditions.

PMID- 23009063
TI  - Stereoselective synthesis of biphenolate/binaphtolate titanate and zirconate
      alkoxide species: structural characterization and use in the controlled ROP of
      lactide.
AB  - Well-defined biphenol/binaphtolate group 4 alkoxide salt species [(Ph-Biphen
      O)(2)M(O(i)Pr)]Li(THF) (2a, M = Ti; 4a, M = Zr) and [(Ph-binapht
      O)(2)M(O(i)Pr)]Li(THF) (2b, M = Ti; 4b, M = Zr) were found to be readily
      accessible in good yields via alcohol elimination routes and/or substitution
      reactions from the corresponding pro-ligands Ph-Biphen-OH (1a) and rac-Ph-Binapht
      OH (1b). As established via X-ray crystallographic analysis, the molecular
      structures of the Ti derivatives 2a and 2b consist of Li(+) salts of anionic Ti
      O(i)Pr moieties in which the Ti center adopts a distorted tbp geometry and is
      effectively chelated by two biphenolate/binaphtolate units. Remarkably, the
      solution and solid state data for salt species 2a,b agree with the sole presence
      of one diastereomer (with a (Delta, aS, aS)/(Lambda, aR, aR) configuration), thus
      indicating that formation of the Ti and Zr alkoxide complexes 2a,b/4a,b proceeds
      stereoselectively. In contrast, the neutral biphenolate/binaphtolate Zr complexes
      (Ph-biphen-O)(2)Zr(THF)(2) (3a) and (Ph-binapht-O)(2)Zr(THF)(2) (3b) were both
      isolated and X-ray characterized as stereomers in a heterochiral configuration
      (Delta, aR, aS)/(Lambda, aS, aR). The Ti and Zr alkoxide anionic chelates were
      found to initiate the ROP of rac-lactide in a controlled manner for production of
      narrowly disperse and ester-end group PLA, as deduced from SEC, kinetic, and
      MALDI-TOF data. The Zr-O(i)Pr derivatives 4a,b exhibit superior performance to
      their Ti counterparts (whether regarding activity, polymerization control, or
      stereoselectivity) to produce narrowly disperse and heterotactically enriched PLA
      (P(r) = 0.67, PDI < 1.15). The significantly decreased Lewis acidity of the Zr
      metal center in anions 4a,b (versus neutral analogues) due to the anionic charge
      and a likely substantial electronic pi donation of the four Zr-O(ArO) oxygens to
      the Zr metal center may rationalize the moderate polymerization activity. Control
      experiments suggest that the nature of the countercation has little influence on
      lactide ROP activity and stereocontrol.

PMID- 23009065
TI  - Stimulus point distribution in deep or superficial peroneal nerve for treatment
      of ankle spasticity.
AB  - OBJECTIVES:  To develop effective electrical stimulation treatment to reduce
      spasticity, we examined the optimal stimulus point of the common peroneal nerve.
      MATERIALS AND METHODS:  The locations of selective stimulus points for the deep
      peroneal nerve or superficial peroneal nerve fiber were examined in 25 healthy
      subjects in both legs (50 legs) using the ratio of the tibialis anterior (TA) to
      the peroneus longus (PL) M-wave amplitude (TA/PL ratio). In addition, we measured
      reciprocal Ia inhibition in ten healthy subjects. The amount of inhibition was
      determined from short-latency suppression of the soleus (Sol) H-reflex by
      conditioning stimuli to the deep or superficial peroneal nerve. The paired t-test
      was used for statistical analysis. RESULTS:  The mean TA/PL ratio during deep
      peroneal nerve stimulation was significantly different from superficial peroneal
      nerve stimulation (p < 0.001). The mean stimulus point for the deep peroneal
      nerve was located 7 +/- 5 mm distal and 3 +/- 6 mm anterior from the distal edges
      of the head of fibula and was markedly different from the stimulus point for the
      superficial peroneal nerve (20 +/- 7 mm distal and 12 +/- 8 mm posterior). During
      deep peroneal nerve stimulation, the mean conditioned H-reflex was depressed to
      83.8 +/- 10.7% of the unconditioned value of the H-reflex. In contrast, during
      superficial peroneal nerve stimulation, the mean conditioned H-reflex increased
      to 105.3 +/- 5.2%. These values were significantly different (p < 0.001).
      CONCLUSIONS:  In the present study, we revealed a stimulus area of the deep
      peroneal nerve. Also, we observed the inhibitory effects of stimulation upon the
      deep peroneal nerve at individual stimulus point. Our results appear to indicate
      that localized stimulation of the deep peroneal nerve is more useful for the
      reduction of ankle spasticity.

PMID- 23009066
TI  - A new self-microemulsifying mouth dissolving film to improve the oral
      bioavailability of poorly water soluble drugs.
AB  - A new self-microemulsifying mouth dissolving film (SMMDF) for poorly water
      soluble drugs such as indomethacin was developed by incorporating self
      microemulsifying components with solid carriers mainly containing
      microcrystalline cellulose, low-substituted hydroxypropyl cellulose and
      hypromellose. The uniformity of dosage units of the preparation was acceptable
      according to the criteria of Chinese Pharmacopoeia 2010. The SMMDF was
      disintegrated within 20 s after immersion into water, released completely at 5
      min in the dissolution medium and achieved microemulsion particle size of 28.81
      +/- 3.26 nm, which was similar to that of liquid self- microemulsifying drug
      delivery system (SMEDDS). Solid state characterization of the SMMDF was performed
      by SEM, DSC and X-ray powder diffraction. Results demonstrated that indomethacin
      in the SMMDF was in the amorphous state, which might be due to self
      microemulsifying ingredients. Pharmacokinetic parameters in rats including
      T(max), C(max), AUC were similar between the SMMDF and liquid SMEDDS. AUC and
      C(max) from the SMMDF were significantly higher than those from the common mouth
      dissolving film or the conventional tablet, and Tmax from SMMDF group was also
      significantly decreased. These findings suggest that the SMMDF is a new promising
      dosage form, showing notable characteristics of convenience, quick onset of
      action and enhanced oral bioavailability of poorly water-soluble drugs.

PMID- 23009067
TI  - Modeling near-edge fine structure X-ray spectra of the manganese catalytic site
      for water oxidation in photosystem II.
AB  - The Mn 1s near-edge absorption fine structure (NEXAFS) has been computed by means
      of transition-state gradient-corrected density functional theory (DFT) on four
      Mn(4)Ca clusters modeling the successive S(0) to S(3) steps of the oxygen
      evolving complex (OEC) in photosystem II (PSII). The model clusters were obtained
      from a previous theoretical study where they were determined by energy
      minimization. They are composed of Mn(III) and Mn(IV) atoms, progressing from
      Mn(III)(3)Mn(IV) for S(0) to Mn(III)(2)Mn(IV)(2) for S(1) to Mn(III)Mn(IV)(3) for
      S(2) to Mn(IV)(4) for S(3), implying an Mn-centered oxidation during each step of
      the photosynthetic oxygen evolution. The DFT simulations of the Mn 1s absorption
      edge reproduce the experimentally measured curves quite well. By the half-height
      method, the theoretical IPEs are shifted by 0.93 eV for the S(0) -> S(1)
      transition, by 1.43 eV for the S(1) -> S(2) transition, and by 0.63 eV for the
      S(2) -> S(3) transition. The inflection point energy (IPE) shifts depend strongly
      on the method used to determine them, and the most interesting result is that the
      present clusters reproduce the shift in the S(2) -> S(3) transition obtained by
      both the half-height and second-derivative methods, thus giving strong support to
      the previously suggested structures and assignments.

PMID- 23009068
TI  - Coeliac disease and C virus-related chronic hepatitis: a non association.
AB  - BACKGROUND: A higher prevalence of coeliac disease has recently been reported
      among patients with HCV-related chronic hepatitis. Moreover, development of
      clinically overt coeliac disease has been described in a number of HCV-related
      chronic hepatitis patients during alpha-interferon therapy. This prospective
      study was designed to evaluate 1) the prevalence of coeliac disease in patients
      with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in
      patients with coeliac disease; 3) whether PEG interferon-alpha treatment might
      favour the development of coeliac disease in patients with chronic hepatitis C.
      MATERIALS AND METHODS: Two hundred-ten consecutive patients (M/F = 140/70, range
      of age 35-58 years, median age 46.5 years) with biopsy proven chronic hepatitis C
      underwent serological screening for antiendomysial and tissue transglutaminase
      IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of
      age 18-74 years, median age 34 years) were screened for HCV antibodies.
      Positivity for HCV antibodies in coeliac disease patients was confirmed by
      detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to
      ethical guidelines of Declaration of Helsinki and was approved by Institutional
      Ethics Committee of the Second University of Naples. All patients gave informed
      written consent. RESULTS: 1) none of the 210 HCV-related chronic hepatitis
      patients were positive for coeliac disease serologic screening; 2) prevalence of
      HCV infection among coeliac patients was 1.54% (3/194) which is comparable to
      that reported in the Southern Italy population; 3) PEG interferon-alpha treatment
      was not associated with development of coeliac disease either clinical or
      serological. CONCLUSIONS: 1) coeliac disease is not associated with HCV
      infection; 2) PEG interferon-alpha does not trigger celiac disease.

PMID- 23009069
TI  - Efficient generation of pyridines by ruthenium carbene mediated [2 + 2 + 2]
      cyclotrimerization.
AB  - Hoveyda-Grubbs' catalyst is able to catalyze crossed [2 + 2 + 2]
      cyclotrimerizations of diynes with nitriles. Pyridines are obtained with
      excellent yields when using activated nitriles and low to moderate yields with
      nonactivated nitriles which are unreactive under previously described ruthenium
      catalyzed reaction conditions. Both terminal and internal alkynes give the
      reaction using this experimental procedure.

PMID- 23009070
TI  - Treatment options for lysosomal storage disorders: developing insights.
AB  - INTRODUCTION: Lysosomal storage disorders (LSDs) are clinically heterogeneous
      disorders that result primarily from lysosomal accumulation of macromolecules in
      various tissues. LSDs are always progressive, and often lead to severe symptoms
      and premature death. The identification of the underlying genetic and enzymatic
      defects has prompted the development of various treatment options. AREAS COVERED:
      To describe the current treatment options for LSDs, the authors provide a focused
      overview of their pathophysiology. They discuss the current applications and
      challenges of enzyme-replacement therapy, stem-cell therapy, gene therapy,
      chaperone therapy and substrate-reduction therapy, as well as future therapeutic
      prospects. EXPERT OPINION: Over recent decades, considerable progress has been
      made in the treatment of LSDs and in the outcome of patients. None of the current
      options are completely curative yet. They are complicated by the difficulty in
      efficiently targeting all affected tissues (particularly the central nervous
      system), in reaching sufficiently high enzyme levels in the target tissues, and
      by their high costs. The pathways leading from the genetic mutation to the
      clinical symptoms should be further elucidated, as they might prompt the
      development of new and ultimately curative therapies.

PMID- 23009072
TI  - Intraspecific variation in mitochondrial genome sequence, structure, and gene
      content in Silene vulgaris, an angiosperm with pervasive cytoplasmic male
      sterility.
AB  - In angiosperms, mitochondrial-encoded genes can cause cytoplasmic male sterility
      (CMS), resulting in the coexistence of female and hermaphroditic individuals
      (gynodioecy). We compared four complete mitochondrial genomes from the
      gynodioecious species Silene vulgaris and found unprecedented amounts of
      intraspecific diversity for plant mitochondrial DNA (mtDNA). Remarkably, only
      about half of overall sequence content is shared between any pair of genomes. The
      four mtDNAs range in size from 361 to 429 kb and differ in gene complement, with
      rpl5 and rps13 being intact in some genomes but absent or pseudogenized in
      others. The genomes exhibit essentially no conservation of synteny and are highly
      repetitive, with evidence of reciprocal recombination occurring even across short
      repeats (< 250 bp). Some mitochondrial genes exhibit atypically high degrees of
      nucleotide polymorphism, while others are invariant. The genomes also contain a
      variable number of small autonomously mapping chromosomes, which have only
      recently been identified in angiosperm mtDNA. Southern blot analysis of one of
      these chromosomes indicated a complex in vivo structure consisting of both
      monomeric circles and multimeric forms. We conclude that S. vulgaris harbors an
      unusually large degree of variation in mtDNA sequence and structure and discuss
      the extent to which this variation might be related to CMS.

PMID- 23009071
TI  - Increasing the open-circuit voltage of photoprotein-based photoelectrochemical
      cells by manipulation of the vacuum potential of the electrolytes.
AB  - The innately highly efficient light-powered separation of charge that underpins
      natural photosynthesis can be exploited for applications in photoelectrochemistry
      by coupling nanoscale protein photoreaction centers to man-made electrodes.
      Planar photoelectrochemical cells employing purple bacterial reaction centers
      have been constructed that produce a direct current under continuous illumination
      and an alternating current in response to discontinuous illumination. The present
      work explored the basis of the open-circuit voltage (V(OC)) produced by such
      cells with reaction center/antenna (RC-LH1) proteins as the photovoltaic
      component. It was established that an up to ~30-fold increase in V(OC) could be
      achieved by simple manipulation of the electrolyte connecting the protein to the
      counter electrode, with an approximately linear relationship being observed
      between the vacuum potential of the electrolyte and the resulting V(OC). We
      conclude that the V(OC) of such a cell is dependent on the potential difference
      between the electrolyte and the photo-oxidized bacteriochlorophylls in the
      reaction center. The steady-state short-circuit current (J(SC)) obtained under
      continuous illumination also varied with different electrolytes by a factor of ~6
      fold. The findings demonstrate a simple way to boost the voltage output of such
      protein-based cells into the hundreds of millivolts range typical of dye
      sensitized and polymer-blend solar cells, while maintaining or improving the
      J(SC). Possible strategies for further increasing the V(OC) of such protein-based
      photoelectrochemical cells through protein engineering are discussed.

PMID- 23009073
TI  - Micro-generation schemes: user behaviours and attitudes towards energy
      consumption.
AB  - In the last decade, there has been increasing pressure on developed nations to
      reduce their carbon emissions. Distributed micro-generation (MG) initiatives
      provide incentives for small-scale renewable energy generation, particularly by
      residential home-owners. This paper investigates the existing knowledge base to
      consider if living in a property with on-site renewable electricity generation
      may affect user attitudes and behaviours. This knowledge is interpreted from a
      human factors perspective by focussing on individual behaviour and social
      learning as well as identifying underlying user requirements and user needs.
      Suggestions are then made with regard to the effects that MG schemes may have on
      public attitudes and where further research efforts should be focused. There is
      evidence that renewable energy initiatives are likely to result in a shift in
      public behaviour, particularly towards reduced energy consumption where
      mechanisms for increased feedback can act as a facilitator to learning and
      motivator to change. PRACTITIONER SUMMARY: The role of human factors/ergonomics
      in supporting renewable energy initiatives has not been fully exploited. A range
      of case studies explore user needs and awareness of renewable energy, presenting
      mixed evidence for reduced consumption. However, individual behaviour and social
      learning can be influenced through increased feedback that acts as a facilitator
      to change.

PMID- 23009074
TI  - Goldmann applanation tonometry compared with corneal-compensated intraocular
      pressure in the evaluation of primary open-angle Glaucoma.
AB  - BACKGROUND: To better understand the role of corneal properties and intraocular
      pressure (IOP) in the evaluation of primary open-angle glaucoma (POAG); and to
      determine the feasibility of identifying glaucomatous optic neuropathy (GON)
      using IOP corrected and uncorrected for corneal biomechanics. METHODS: Records
      from 1,875 eyes of consecutively evaluated new patients were reviewed. Eyes were
      excluded if central corneal thickness (CCT) or Ocular Response Analyzer (ORA)
      measurements were unavailable. Presence or absence of GON was determined based on
      morphology of the optic disc, rim and retinal nerve fiber layer at the time of
      clinical examination, fundus photography and Heidelberg Retinal Tomography.
      Goldmann-applanation tonometry (GAT) in the untreated state was recorded and
      Goldmann-correlated (IOPg) and corneal-compensated IOP (IOPcc) were obtained
      using the ORA. Glaucomatous eyes were classified as normal or high-tension (NTG,
      HTG) using the conventional cutoff of 21 mm Hg. One eligible eye was randomly
      selected from each patient for inclusion. RESULTS: A total of 357 normal, 155 HTG
      and 102 NTG eyes were included. Among NTG eyes, IOPcc was greater than GAT (19.8
      and 14.4 mm Hg; p < 0.001) and the difference between IOPcc and GAT was greatest
      for this subgroup of patients with NTG (p <= 0.01). The maximum combined
      sensitivity and specificity for detection of GON occurred at 20.9 mm Hg for GAT
      (59%, 90%) and 18.4 mm Hg for IOPcc (85%, 85%) and the area under the curve was
      greater for IOPcc (0.93 vs. 0.78; p < 0.001). CONCLUSIONS: IOPcc may account for
      measurement error induced by corneal biomechanics. Compared to GAT, IOPcc may be
      a superior test in the evaluation of glaucoma but is unlikely to represent an
      effective diagnostic test.

PMID- 23009076
TI  - Top-Hat HELLISH-VCSOA for optical amplification and wavelength conversion for
      0.85 to 1.3MUm operation.
AB  - The Top-Hat hot electron light emission and lasing in semiconductor
      heterostructure (HELLISH)-vertical cavity semiconductor optical amplifier (VCSOA)
      is a modified version of a HELLISH-VCSOA device. It has a shorter p-channel and
      longer n-channel. The device studied in this work consists of a simple GaAs p-i-n
      junction, containing 11 Ga0.35In0.65 N0.02As0.08/GaAs multiple quantum wells in
      its intrinsic region; the active region is enclosed between six pairs of
      GaAs/AlAs top distributed Bragg reflector (DBR) mirrors and 20.5 pairs of
      AlAs/GaAs bottom DBR mirrors. The operation of the device is based on
      longitudinal current transport parallel to the layers of the GaAs p-n junction.
      The device is characterised through I-V-L and by spectral photoluminescence,
      electroluminescence and electro-photoluminescence measurements. An amplification
      of about 25 dB is observed at applied voltages of around V = 88 V.

PMID- 23009075
TI  - The knowledge, attitude and behavior about public health emergencies and the
      response capacity of primary care medical staffs of Guangdong Province, China.
AB  - BACKGROUND: Primary care medical staffs' knowledge, attitude and behavior about
      health emergency and the response capacity are directly related to the control
      and prevention of public health emergencies. Therefore, it is of great
      significance for improving primary care to gain in-depth knowledge about
      knowledge, attitude and behavior and the response capacity of primary care
      medical staffs. The main objective of this study is to explore knowledge,
      attitude and behavior, and the response capacity of primary care medical staffs
      of Guangdong Province, China. METHODS: Stratified clustered sample method was
      used in the anonymous questionnaire investigation about knowledge, attitude and
      behavior, and the response capacity of 3410 primary care medical staffs in 15
      cities of Guangdong Province, China from July, 2010 to October 2010. The
      emergency response capacity was evaluated by 33 questions. The highest score of
      the response capacity was 100 points (full score), score of 70 was a standard.
      RESULTS: 62.4% primary care medical staffs believed that public health
      emergencies would happen. Influenza (3.86 +/- 0.88), food poisoning (3.35 +/-
      0.75), and environmental pollution events (3.23 +/- 0.80) (the total score was 5)
      were considered most likely to occur. Among the 7 public health emergency skills,
      the highest self-assessment score is "public health emergency prevention skills"
      (2.90 +/- 0.68), the lowest is "public health emergency risk management (the
      total score was 5)" (1.81 +/- 0.40). Attitude evaluation showed 66.1% of the
      medical staffs believed that the community awareness of risk management were
      ordinary. Evaluation of response capacity of health emergency showed that the
      score of primary care medical staffs was 67.23 +/- 10.61, and the response
      capacity of senior physicians, public health physicians and physicians with
      relatively long-term practice were significantly better (P <0.05). Multiple
      linear stepwise regression analysis showed gender, title, position, type of work,
      work experience and whether to participate relative training were the main
      factors affecting the health emergency response capacity. CONCLUSIONS: The
      knowledge, attitude and behavior about public health emergencies and the response
      capacity of primary care medical staffs of Guangdong Province (China) were poor.
      Health administrative departments should strengthen the training of health
      emergency knowledge and skills of the primary care medical staffs to enhance
      their health emergency response capabilities.

PMID- 23009077
TI  - Costs and benefits of trap-neuter-release and euthanasia for removal of urban
      cats in Oahu, Hawaii.
AB  - Our goal was to determine whether it is more cost-effective to control feral cat
      abundance with trap-neuter-release programs or trap and euthanize programs. Using
      STELLA 7, systems modeling software, we modeled changes over 30 years in
      abundance of cats in a feral colony in response to each management method and the
      costs and benefits associated with each method . We included costs associated
      with providing food, veterinary care, and microchips to the colony cats and the
      cost of euthanasia, wages, and trapping equipment in the model. Due to a lack of
      data on predation rates and disease transmission by feral cats the only benefits
      incorporated into the analyses were reduced predation on Wedge-tailed Shearwaters
      (Puffinus pacificus). When no additional domestic cats were abandoned by owners
      and the trap and euthanize program removed 30,000 cats in the first year, the
      colony was extirpated in at least 75% of model simulations within the second
      year. It took 30 years for trap-neuter-release to extirpate the colony. When the
      cat population was supplemented with 10% of the initial population size per year,
      the colony returned to carrying capacity within 6 years and the trap and
      euthanize program had to be repeated, whereas trap-neuter-release never reduced
      the number of cats to near zero within the 30-year time frame of the model. The
      abandonment of domestic cats reduced the cost effectiveness of both trap-neuter
      release and trap and euthanize. Trap-neuter-release was approximately twice as
      expensive to implement as a trap and euthanize program. Results of sensitivity
      analyses suggested trap-neuter-release programs that employ volunteers are still
      less cost-effective than trap and euthanize programs that employ paid
      professionals and that trap-neuter-release was only effective when the total
      number of colony cats in an area was below 1000. Reducing the rate of abandonment
      of domestic cats appears to be a more effective solution for reducing the
      abundance of feral cats.

PMID- 23009078
TI  - An adolescent patient with post-thrombotic syndrome achieves excellence in sport.
AB  - The reported incidence of post-thrombotic syndrome (PTS) following deep venous
      thrombosis (DVT) in children has increased. Diagnosis of PTS is reliant on
      assessment of clinical signs and self-report of physical symptoms. We present the
      case of an 11-year-old young man, diagnosed with a spontaneous lower-limb DVT,
      who developed significant clinical signs of severe PTS with no apparent physical
      symptoms. In adolescence, the patient participated in high-level competitive
      sport with no reported functional limitations. This case highlights that reliance
      on the severity of only clinical signs without an understanding of a child's
      physical abilities limits the assessment of PTS.

PMID- 23009079
TI  - Investigating linkage rates among probabilistically linked birth and
      hospitalization records.
AB  - BACKGROUND: With the increasing use of probabilistically linked administrative
      data in health research, it is important to understand whether systematic
      differences occur between the populations with linked and unlinked records. While
      probabilistic linkage involves combining records for individuals, population
      perinatal health research requires a combination of information from both the
      mother and her infant(s). The aims of this study were to (i) describe
      probabilistic linkage for perinatal records in New South Wales (NSW) Australia,
      (ii) determine linkage proportions for these perinatal records, and (iii) assess
      records with linked mother and infant hospital-birth record, and unlinked records
      for systematic differences. METHODS: This is a population-based study of
      probabilistically linked statutory birth and hospital records from New South
      Wales, Australia, 2001-2008. Linkage groups were created where the birth record
      had complete linkage with hospital admission records for both the mother and
      infant(s), partial linkage (the mother only or the infant(s) only) or neither.
      Unlinked hospital records for mothers and infants were also examined. Rates of
      linkage as a percentage of birth records and descriptive statistics for maternal
      and infant characteristics by linkage groups were determined. RESULTS: Complete
      linkage (mother hospital record - birth record - infant hospital record) was
      available for 95.9% of birth records, partial linkage for 3.6%, and 0.5% with no
      linked hospital records (unlinked). Among live born singletons (complete linkage
      = 96.5%) the mothers without linked infant records (1.6%) had slightly higher
      proportions of young, non-Australian born, socially disadvantaged women with
      adverse pregnancy outcomes. The unlinked birth records (0.4%) had slightly higher
      proportions of nulliparous, older, Australian born women giving birth in private
      hospitals by caesarean section. Stillbirths had the highest rate of unlinked
      records (3-4%). CONCLUSIONS: This study shows that probabilistic linkage of
      perinatal records can achieve high, representative levels of complete linkage.
      Records for mother's that did not link to infant records and unlinked records had
      slightly different characteristics to fully linked records. However, these groups
      were small and unlikely to bias results and conclusions in a substantive way.
      Stillbirths present additional challenges to the linkage process due to lower
      rates of linkage for lower gestational ages, where most stillbirths occur.

PMID- 23009081
TI  - Toward the characterization of fractional stochastic processes underlying methyl
      dynamics in proteins.
AB  - In this article, we investigate the multiple-scale structure of methyl side chain
      dynamics in proteins. We show that the orientational correlation functions of
      CH(3) methyl groups are well described by a fractional Brownian dynamics model.
      Typical angular correlation functions involved in NMR relaxation were computed
      from MD simulations performed on two different proteins. These correlation
      functions were shown to be very well fitted by a fractional Ornstein-Uhlenbeck
      process in the presence of effective local potentials at the C-H and C-C methyl
      bonds. In addition, our analysis highlights the presence of the asymptotic power
      law decay of the waiting time probability density of the stochastic process
      involved, thereby illustrating the connection between approaches based on
      fractional diffusion equations and the continuous time random walk.

PMID- 23009082
TI  - A snapshot of guideline compliance reveals room for improvement: a survey of
      peripheral arterial catheter practices in Australian operating theatres.
AB  - AIM: To report a study in Australian operating theatres of compliance by the
      anaesthetic team with best peripheral arterial catheter practice for blood gas
      sampling and infection prevention. Comparisons are made with research
      recommendations and Centres for Disease Control Guidelines. BACKGROUND: There is
      wide global usage of peripheral arterial catheters in the operating theatre for
      haemodynamic monitoring and blood gas analysis. Frequent blood sampling from
      arterial catheters can lead to statistically significant blood loss and provide
      an infective potential. Evidence-based research and clinical guidelines prescribe
      best practice. DESIGN: Cross-sectional descriptive survey METHODS: Data were
      collected in 2009 from 64 major Australian hospitals using a self-designed
      internet survey. RESULTS/FINDINGS: Hand hygiene prior to catheter insertion was
      the only infection prevention practice entirely adherent with guidelines. The
      recommended ratio of discard to dead space volume of 2:1 to decrease unnecessary
      blood loss during blood gas sampling was reported by only 11 (17%) respondents.
      Less than 32 (50%) respondents used the preferred solution, chlorhexidine to
      disinfect the insertion site. Access ports were reported as 'never disinfected'
      before use by 30 (47%) respondents. CONCLUSION: The complex operating theatre
      environment presents barriers, which contribute to non-adherence with guidelines.
      These barriers need to be identified to plan strategies for improvement. A
      quality audit tool is proposed for development by nurses in collaboration with
      the anaesthetic team, providing a needed method to assess ongoing compliance with
      best peripheral arterial catheter care. Further international research would test
      the generalizability of our Australian findings.

PMID- 23009083
TI  - Psychosocial oncofertility issues faced by adolescents and young adults over
      their lifetime: a review of the research.
AB  - This review considers psychosocial oncofertility research relevant to adolescents
      and young adults over their lifetime. There is growing awareness of the fertility
      preservation needs of younger males including lowering practical barriers and
      attending to emotional impact. Despite decisional challenges facing females--the
      experimental nature of procedures, time involved and potential involvement of
      partners/donors (for embryo cryopreservation)--findings suggest they too benefit
      from fertility information at diagnosis and access to fertility specialists.
      Studies consistently report that fertility concerns affect well-being,
      relationships and life planning. Both genders thus want fertility issues to be
      raised proactively by professionals in the years following diagnosis: to help
      them make informed decisions at a time relevant to them, develop coping
      strategies for current and future related areas and to be referred to specialist
      and/or therapeutic help if needed. Little is known about why cancer survivors are
      less likely to marry or have children, or about their parenthood experiences.

PMID- 23009084
TI  - Vaginal distribution and retention of tablets comprising starch-based
      multiparticulates: evaluation by colposcopy.
AB  - We have developed fast-disintegrating tablets comprising starch-based pellets and
      excipient granules for intravaginal drug delivery. The purpose of this study was
      to evaluate the intravaginal disintegration, distribution and retention behavior
      of these tablets in sheep and women using colposcopy as visualization technique.
      One tablet was administered to each study subject (n = 6) and repeated colposcopy
      examination was performed over a 48 h and 24 h period in sheep and women,
      respectively. Colposcopy in sheep indicated that in vivo tablet disintegration
      was initiated within 30 min of vaginal administration and that due to
      disintegration of the pellets themselves, the formulation was transformed into a
      gel-like mass which distributed throughout the entire vaginal cavity within 2-4
      h. In vivo tablet disintegration after intravaginal administration to women was
      complete within 4 h, whereby the formulation gradually spread throughout the
      vaginal cavity as complete covering was observed after 12 and 24 h. The
      persistent retention (up to 24 and 48 h in women and sheep, respectively)
      confirmed the long retention time of this vaginal formulation. 

PMID- 23009085
TI  - Emergency presentation of the gastric cancer; prognosis and implications for
      service planning.
AB  - AIMS: To compare emergency and elective presentation of gastric cancer by mode of
      clinical presentation, initial stage, intervention and prognosis. METHODS: Data
      were collected prospectively for all cases of gastric cancer presenting to a
      tertiary referral centre between 2003 and 2010. This was stratified by emergency
      and elective presentation and was analysed for mode of presentation, initial
      stage and outcome. Statistical analysis was performed using unpaired t-test and
      Chi2 test. RESULTS: A total of 291 patients presented: Forty-two (14.43%) were
      emergencies and 249 (85.57%) elective presentations. Analysis of the emergency
      cohort showed 25 patients presented with obstruction (59.52%), 15 presented with
      haematemesis (35.71%) and 2 with perforation (4.76%).Eighteen of the emergency
      patients (45%) presented with stage 4 disease compared to 60 (25.42%) in the
      elective group (p < 0.005). Fourteen of the emergency patients were treated with
      curative intent (33.3%) compared with 130 (55.56%) in the elective group (p <
      0.01). Over 6 years only 2 patients needed operation within 24 hours of
      presentation.Overall survival at one year for emergency patients was 48.3%
      compared to 63.4% in elective patients (p < 0.05). There were no survivors from
      the emergency group after 3 years but 32.46% of the elective patients survived (p
      < 0.02). Elective presentation with disease stage 1A-3B had a two year survival
      rate of 54.95% compared to only 20% in the emergency group (p < 0.05). Of
      patients who underwent operative intervention 67.44% of patients who presented
      electively survived to 2 years. This compared to just 25% presenting as
      emergencies (p < 0.001). CONCLUSIONS: Emergency presentation of gastric cancer is
      rare; is associated with higher stage of disease at presentation and lower rates
      of operability. The necessity to perform emergency operation within 24 hours is
      exceedingly rare. Emergency presentation is a marker of poor long term outcome
      for equivalent cancer stage in non-advanced (stages 1A-3B) disease.

PMID- 23009086
TI  - Modified metaphyseal-loading anterolaterally flared anatomic femoral stem: five-
      to nine-year prospective follow-up evaluation and results of three-dimensional
      finite element analysis.
AB  - We have designed a proximal-fitting, anterolaterally flared, arc-deposit
      hydroxyapatite-coated anatomical femoral stem (FMS-anatomic stem; KYOCERA
      Medical, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese
      patients with dysplastic hip osteoarthritis, using a nonlinear three-dimensional
      finite element analysis simulating loading conditions. The Anatomic Fit stem was
      modified in the region of the arc-sprayed surface, to allow more proximal
      appearance of spot welds. The aim of the present study was to analyze the
      clinical and radiographic outcomes of patients who underwent THA using this stem.
      We reviewed 73 consecutive patients (79 hips; 13 men 16 hips; 60 women 63 hips;
      age at surgery, 57.6 years, range, 35-78) who underwent cementless THA using the
      Anatomic Fit stem, at a follow-up period of 7.1 years (range, 5.1-9.4). Harris
      Hip score improved from 40.7 +/- 17.1 before surgery to 91.0 +/- 5.2 points at
      follow-up. The 7.1-year stem survival rate was 100%. Radiographs at follow-up
      confirmed the stability of the femoral stems within the femoral canal in all
      cases, with sufficient bone ingrowth. None of the patients had subsidence of the
      stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus
      position of more than 2.0 degrees . The Anatomic Fit stem provided excellent
      results. The nonlinear three-dimensional finite element analysis demonstrated
      that the stem-bone relative motion was 10 um at the proximal end of the stem and
      proximal load transfer. Our analysis confirmed reduced radiolucency around the
      stem, minimal subsidence, appropriate stress shielding, and promising medium-term
      stability within the femoral canal.

PMID- 23009087
TI  - Quenching dynamics in CdSe nanoparticles: surface-induced defects upon dilution.
AB  - We have analyzed the decays of the fluorescence of colloidal CdSe quantum dots
      (QDs) suspensions during dilution and titration by the ligands. A ligand shell
      made of a combination of trioctylphosphine (TOP), oleylamine (OA), and stearic
      acid (SA) stabilizes the as-synthesized QDs. The composition of the shell was
      analyzed and quantified using high resolution liquid state 1H nuclear magnetic
      resonance (NMR) spectroscopy. A quenching of the fluorescence of the QDs is
      observed upon removal of the ligands by diluting the stock solution of the QDs.
      The fluorescence is restored by the addition of TOP. We analyze the results by
      assuming a binomial distribution of quenchers among the QDs and predict a linear
      trend in the time-resolved fluorescence decays. We have used a nonparametric
      analysis to show that for our QDs, 3.0 +/- 0.1 quenching sites per QD on average
      are revealed by the removal of TOP. We moreover show that the quenching rates of
      the quenching sites add up. The decay per quenching site can be compared with the
      decay at saturation of the dilution effect. This provides a value of 2.88 +/-
      0.02 for the number of quenchers per QD. We extract the quenching dynamics of one
      site. It appears to be a process with a distribution of rates that does not
      involve the ligands.

PMID- 23009088
TI  - Approaches to Ras signaling modulation and treatment of Ras-dependent disorders:
      a patent review (2007--present).
AB  - INTRODUCTION: Ras proteins are small GTPases molecular switches that cycle
      through two alternative conformational states, a GDP-bound inactive state and a
      GTP-bound active state. In the active state, Ras proteins interact with and
      modulate the activity of several downstream effectors regulating key cellular
      processes including proliferation, differentiation, survival, senescence,
      migration and metabolism. Activating mutations of RAS genes and of genes encoding
      Ras signaling members have a great incidence in proliferative disorders, such as
      cancer, immune and inflammatory diseases and developmental syndromes. Therefore,
      Ras and Ras signaling represent important clinical targets for the design and
      development of pharmaceutically active agents, including anticancer agents. AREAS
      COVERED: The authors summarize methods available to down-regulate the Ras pathway
      and review recent patents covering Ras signaling modulators, as well as methods
      designed to kill specifically cancer cells bearing activated RAS oncogene. EXPERT
      OPINION: Targeted therapy approach based on direct targeting of molecules
      specifically altered in Ras-dependent diseases is pursued with molecules that
      down-regulate expression or inhibit the biological function of mutant Ras or Ras
      signaling members. The low success rate in a clinical setting of molecules
      targeting activated members of the Ras pathway may require development of novel
      approaches, including combined and synthetic lethal therapies.

PMID- 23009089
TI  - Correcting Indigenous Australians' refractive error and presbyopia.
AB  - BACKGROUND: This paper aims to identify the barriers and solutions for refractive
      error and presbyopia vision correction for Indigenous Australians. DESIGN: A
      qualitative study, using semistructured interviews, focus groups, stakeholder
      workshops and consultation, conducted in community, private practice, hospital,
      non-government organization and government settings. PARTICIPANTS: Five hundred
      and thirty-one people participated in consultations. METHODS: Data were collected
      at 21 sites across Australia. Semistructured interviews were conducted with 289
      people working in Indigenous health and eye care sectors; focus group discussions
      with 81 community members; stakeholder workshops involving 86 individuals; and
      separate meetings with 75 people. Barriers were identified through thematic
      analysis and policy solutions developed through iterative consultation. MAIN
      OUTCOME MEASURES: Barriers and solutions to remedy Indigenous Australians'
      uncorrected refractive error and presbyopia. RESULTS: Indigenous Australians'
      uncorrected refractive error and presbyopia can be eliminated through improvement
      of primary care identification and referral of people with poor vision, increased
      availability of optometry services in Aboriginal Health Services, introduction of
      a nationally consistent Indigenous subsidized spectacle scheme and proper
      coordination, promotion and monitoring of these services. CONCLUSIONS: The
      refractive error and presbyopia correction needs of Indigenous Australians are
      immediately treatable by the simple provision of glasses. The workforce capacity
      exists to provide the eye exams to prescribe glasses and the cost is modest. What
      is required is identification of patients with refractive needs within community,
      referral to accessible optometry services, a good supply system for appropriate
      and affordable glasses and the coordination and integration of this service
      within a broader eye care system.

PMID- 23009090
TI  - Thermal stability and ordering study of long- and short-alkyl chain phosphonic
      acid multilayers.
AB  - Long-range order evolution of self-assembled phosphonic acid multilayers as a
      function of temperature is studied here for two molecules with different alkyl
      chain length. By using synchrotron conventional diffraction, distinct order
      configurations are retrieved on phosphonic acid multilayers and their
      thermodynamic behavior monitored by energy-dispersive diffraction. This later
      technique allows us to observe the system behavior near order-disorder
      temperatures, as well as to determine the most stable configurations in the range
      from room temperature up to 120  degrees C. Planar order is also addressed by
      wide-angle X-ray scattering (WAXS) transmission experiments. Order parameter
      phase diagrams are built based on the experimental results, showing the dominant
      configuration at each temperature. The multilayer molecular long-range order
      retrieved from the experiments is corroborated by first principles calculations
      based on the Density Functional Theory. The bulk configurations depicted in this
      work are produced by molecule-molecule interactions and allow for future
      comparisons with the behavior of ordered molecules in few-monolayers
      configurations, commonly used in organic devices, where the presence of surfaces
      and interfaces strongly affects the molecule packing.

PMID- 23009091
TI  - Predicting interactions among fishing, ocean warming, and ocean acidification in
      a marine system with whole-ecosystem models.
AB  - An important challenge for conservation is a quantitative understanding of how
      multiple human stressors will interact to mitigate or exacerbate global
      environmental change at a community or ecosystem level. We explored the
      interaction effects of fishing, ocean warming, and ocean acidification over time
      on 60 functional groups of species in the southeastern Australian marine
      ecosystem. We tracked changes in relative biomass within a coupled dynamic whole
      ecosystem modeling framework that included the biophysical system, human effects,
      socioeconomics, and management evaluation. We estimated the individual, additive,
      and interactive effects on the ecosystem and for five community groups (top
      predators, fishes, benthic invertebrates, plankton, and primary producers). We
      calculated the size and direction of interaction effects with an additive null
      model and interpreted results as synergistic (amplified stress), additive (no
      additional stress), or antagonistic (reduced stress). Individually, only ocean
      acidification had a negative effect on total biomass. Fishing and ocean warming
      and ocean warming with ocean acidification had an additive effect on biomass.
      Adding fishing to ocean warming and ocean acidification significantly changed the
      direction and magnitude of the interaction effect to a synergistic response on
      biomass. The interaction effect depended on the response level examined
      (ecosystem vs. community). For communities, the size, direction, and type of
      interaction effect varied depending on the combination of stressors. Top predator
      and fish biomass had a synergistic response to the interaction of all three
      stressors, whereas biomass of benthic invertebrates responded antagonistically.
      With our approach, we were able to identify the regional effects of fishing on
      the size and direction of the interacting effects of ocean warming and ocean
      acidification.

PMID- 23009092
TI  - O'3-Na(x)VO2 system: a superstructure for Na(1/2)VO2.
AB  - The electrochemical cycling in a sodium battery of the lamellar oxide NaVO(2) is
      reversible in the Na(x)VO(2) composition range 1/2 <= x <= 1. The complex
      electrochemical curve reveals the presence of several transitions taking place
      during deintercalation. With the help of in situ X-ray diffraction, we observed
      the structural transitions taking place between Na(2/3)VO(2) and Na(1/2)VO(2).
      The diffractograms show the presence of several monophasic domains separated by
      biphasic domains. All phases present a monoclinic distortion of the alpha
      NaFeO(2) structure in the composition range 1/2 <= x <= 2/3. Moreover the
      presence of a superstructure is evidenced for Na(1/2)VO(2). It is the first time
      that an ordered structure is reported at the Na(1/2)MO(2) composition with an O'3
      oxygen stacking. A thorough investigation of electrochemically obtained O'3
      Na(1/2)VO(2) was performed. The structure refinement reveals the existence of a
      sodium/vacancy ordering, with a peculiar arrangement of the V-V distances hinting
      at a pairing of vanadium atoms. Our first measurements of the physical properties
      of O'3-Na(1/2)VO(2) show a semiconductor behavior and a complex thermal
      dependence of the magnetic susceptibility related to the pairing of the vanadium
      atoms.

PMID- 23009094
TI  - Analysis of HLA-G polymorphisms in couples with implantation failure.
AB  - PROBLEM: HLA-G expression is related as an immune modulator of fetal-maternal
      tolerance, and its levels was correlated with pregnancy outcome. In a case
      control study, we investigate the association between the genetic variability of
      the HLA-G gene and serum levels of soluble HLA-G in cases of embryo implantation
      failure. METHOD OF STUDY: Forty couples with at least two unsuccessful fresh
      embryo transfers (implantation failure; IF) and 83 fertile couples with at least
      two successful pregnancies was genotyped by sequencing-based typing. HLA-G
      alleles were defined by nucleotide sequence variations at exon 2, 3, and 4, and
      the quantification of soluble HLA-G (sHLA-G) was performed by ELISA. RESULTS:
      There was a significant difference between the HLA-G allelic distributions
      between IF couples and the control couples. The HLA-G*01:03:01 allele was
      increased in the IF couples. There were no significant differences in the serum
      levels of sHLA-G in the IF and control groups. CONCLUSION: The results suggest
      that the distribution of HLA-G products may play a significant role in the
      modulation of maternal-fetal immune response.

PMID- 23009093
TI  - Decrypting cryptochrome: revealing the molecular identity of the photoactivation
      reaction.
AB  - Migrating birds fly thousands of miles or more, often without visual cues and in
      treacherous winds, yet keep direction. They employ for this purpose, apparently
      as a powerful navigational tool, the photoreceptor protein cryptochrome to sense
      the geomagnetic field. The unique biological function of cryptochrome supposedly
      arises from a photoactivation reaction involving radical pair formation through
      electron transfer. Radical pairs, indeed, can act as a magnetic compass; however,
      the cryptochrome photoreaction pathway is not fully resolved yet. To reveal this
      pathway and underlying photochemical mechanisms, we carried out a combination of
      quantum chemical calculations and molecular dynamics simulations on plant (
      Arabidopsis thaliana ) cryptochrome. The results demonstrate that after
      photoexcitation a radical pair forms, becomes stabilized through proton transfer,
      and decays back to the protein's resting state on time scales allowing the
      protein, in principle, to act as a radical pair-based magnetic sensor. We briefly
      relate our findings on  A. thaliana  cryptochrome to photoreaction pathways in
      animal cryptochromes.

PMID- 23009095
TI  - Use of selected ambulatory dental services in Taiwan before and after global
      budgeting:  a longitudinal study to identify trends in hospital and clinic-based
      services.
AB  - BACKGROUND: The Taiwan government adopted National Health Insurance (NHI) in
      1995, providing universal health care to all citizens. It was financed by
      mandatory premium contributions made by employers, employees, and the government.
      Since then, the government has faced increasing challenges to control NHI
      expenditures. The aim of this study was to determine trends in the provision of
      dental services in Taiwan after the implementation of global budgeting in 1998
      and to identify areas of possible concern. METHODS: This longitudinal
      before/after study was based on data from the National Health Insurance Research
      Database from 1996 to 2001. These data were subjected to logistic regression
      analysis. Linear regression analysis was used to examine changes in delivery of
      specific services after global budgeting implementation. Utilization of hospital
      and clinic services was compared. RESULTS: Reimbursement for dental services
      increased significantly while the number of visits per patient remained steady in
      both hospitals and clinics. In hospitals, visits for root canal procedures,
      ionomer restoration, tooth extraction and tooth scaling increased significantly.
      In dental clinics, visits for amalgam restoration decreased significantly while
      those for ionomer restoration, tooth extraction, and tooth scaling increased
      significantly. After the adoption of global budgeting, expenditures for dental
      services increased dramatically while the number of visits per patient did not,
      indicating a possible shift in patients to hospital facilities that received
      additional National Health Insurance funding. CONCLUSIONS: The identified trends
      indicate increased utilization of dental services and uneven distribution of care
      and dentists. These trends may be compromising the quality of dental care
      delivered in Taiwan.

PMID- 23009096
TI  - Adhesion GPCRs are widely expressed throughout the subsections of the
      gastrointestinal tract.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) represent one of the largest
      families of transmembrane receptors and the most common drug target. The Adhesion
      subfamily is the second largest one of GPCRs and its several members are known to
      mediate neural development and immune system functioning through cell-cell and
      cell-matrix interactions. The distribution of these receptors has not been
      characterized in detail in the gastrointestinal (GI) tract. Here we present the
      first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion
      GPCRs in the rat GI tract divided into twelve subsegments. METHODS: Using RT
      qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus
      and antrum of the stomach, the proximal and distal parts of the duodenum, ileum,
      jejunum and colon, and the cecum. RESULTS: We found that twenty-one Adhesion
      GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous
      (expressed in eleven or more segments) distribution, seven (23%) were restricted
      to a few segments of the GI tract and two were not expressed in any segment. Most
      notably, almost all Group III members were ubiquitously expressed, while the
      restricted expression was characteristic for the majority of group VII members,
      hinting at more specific/localized roles for some of these receptors.
      CONCLUSIONS: Overall, the distribution of Adhesion GPCRs points to their
      important role in GI tract functioning and defines them as a potentially crucial
      target for pharmacological interventions.

PMID- 23009097
TI  - Multiple regulation of Arabidopsis AtGST11 gene expression by four transcription
      factors under abiotic stresses.
AB  - The Arabidopsis thaliana glutathione S-transferase (GST; E.C. 2.5.1.18) gene,
      AtGST11, is regulated by a number of environmental stresses, including metal
      toxicities, oxidative stress and extremes of temperature. To clarify the
      mechanisms of this regulation, two transcription factors [(TFs), P1-1 and P1-3]
      were isolated by yeast one-hybrid (Y1H) analysis and characterized. These TFs
      encoded a putative bZIP TF (AtbZIP30) and ethylene-response element-binding
      factor 2 (AtERF2), respectively. Y1H and electrophoresis mobility shift assay
      (EMSA) showed that both proteins bound to the 5'-upstream region of the AtGST11
      gene. Promoter activity assays indicated that both TFs upregulate AtGST11. In
      addition, another two previously isolated TFs (#13 and #43), encoding C3 HC4 
      type RING finger (DAL1) and Homeobox protein 6 (AtHB6), respectively, were found
      to downregulate. Expression of the AtGST11 gene in a wild-type line (Col-0) was
      increased by Cd, Cu and Al, but decreased by cold, heat and diamide treatment. To
      determine how each TF relates to the environmental regulation of the AtGST11
      gene, quantitative real-time polymerase chain reaction was performed using RNA
      samples derived from two disrupted mutant lines (DeltaDAL1 and DeltaAtHB6) or an
      over-expression line (oxAtERF2) under various stresses. The results indicated
      that DAL1 and AtHB6 downregulated the expression of AtGST11 under, most of the
      stresses tested as, repressors and AtERF2 upregulated the expression under heat
      stress as inducer.

PMID- 23009098
TI  - Human myometrium - the ultrastructural 3D network of telocytes.
AB  - Telocytes (TCs), a novel type of interstitial cells, were recently described in
      the interstitial space of tissues (www.telocytes.com). Telocytes TCs have several
      very long, moniliform extensions, namely telopodes (Tps). However, the functional
      role(s) of TCs is not yet understood. Successive photomicrographs of ultrathin
      sections were concatenated to capture the entire length of Tps which usually
      measure tens to hundreds of micrometres. Besides the podoms (dilations) and
      podomers (thin segments), ultrastructural features of Tps include the dichotomous
      branching and establishing homo- and heterocellular contacts. Telopodes make a
      labyrinthine system by 3D convolution and overlapping, their number being roughly
      estimated at approximately 20 per 1000 MUm(2) . Moreover, the presence of
      extracellular vesicles (shedding vesicles/exosomes) along the Tps suggests an
      active intercellular signalling (micro- and macromolecules), with possible
      significance in regulating uterine contractility.

PMID- 23009100
TI  - Formation of surface relief gratings:  effect of the density of the host
      material.
AB  - We use molecular dynamics simulations to investigate the effect of the density of
      the host material on the isomerization-induced diffusion mechanism that results
      in surface relief gratings formation. We find that a decrease in density
      increases the diffusion coefficient in a similar way for  driven and  spontaneous
      diffusion. This result suggests that the driving mechanism depends only slightly
      on the density of the host material. The pressure variations during the
      isomerization process decrease when the driven diffusion increases due to
      material softening for smaller densities. These results suggest that the pressure
      variations are not at the origin of the driven motions. The relative local
      density variation around the probe is also weakly dependent on the mean density
      of the host material as long as the material structure is preserved.

PMID- 23009099
TI  - Attraction of the cutaneous leishmaniasis vector Nyssomyia neivai (Diptera:
      Psychodidae) to host odour components in a wind tunnel.
AB  - BACKGROUND: Laboratory studies of host-seeking olfactory behaviour in sandflies
      have largely been restricted to the American visceral leishmaniasis vector
      Lutzomyia longipalpis. In comparison, almost nothing is known about the chemical
      ecology of related species, which transmit American cutaneous leishmaniasis
      (ACL), due in part to difficulties in raising these insects in the laboratory.
      Understanding how ACL vectors locate their hosts will be essential to developing
      new vector control strategies to combat this debilitating disease. METHODS: This
      study examined host-odour seeking behaviour of the ACL vector Nyssomyia neivai
      (Pinto) (=Lutzomyia neivai) using a wind tunnel olfactometer. The primary aim was
      to determine whether field-collected female N. neivai would respond to host
      odours in the laboratory, thereby eliminating the need to maintain colonies of
      these insects for behavioural experiments. Responses to two key host odour
      components, 1-octen-3-ol and lactic acid, and a commercially-available mosquito
      lure (BG-LureTM) were assessed and compared relative to an air control. We also
      tested whether trials could be conducted outside of the normal evening activity
      period of N. neivai without impacting on fly behaviour, and whether the same
      flies could be used to assess baseline responses to air without affecting
      responses to octenol, thereby reducing the number of flies required for
      experiments. RESULTS: Octenol was found to both activate host-seeking behaviour
      and attract female N. neivai in the wind tunnel, while lactic acid elicited
      weaker responses of activation and attractiveness under identical conditions. The
      BG-Lure did not activate or attract N. neivai under test conditions. Further
      experiments showed that sandfly behaviour in the wind tunnel was not affected by
      time of day, such that experiments need not be restricted to nocturnal hours.
      Moreover, using the same flies to measure both baseline responses to air and
      attraction to test compounds did not affect odour-seeking behaviour. CONCLUSIONS:
      The results of this study demonstrate that N. neivai taken from the field are
      suitable for use in laboratory olfactometer experiments. It is hoped this work
      will facilitate further research into chemical ecology of this species, and other
      ACL vectors.

PMID- 23009101
TI  - Telomere length is shorter in affected members of families with familial
      nonmedullary thyroid cancer.
AB  - BACKGROUND: The theory that short telomere length and genetic defects in
      maintaining telomere length are associated with familial nonmedullary thyroid
      cancer (FNMTC) is controversial. Thus, the aim of this study was to determine
      whether telomere length and genes involved in maintaining telomere length are
      altered in FNMTC. METHODS: Blood samples were collected from 44 members (13
      affected and 31 unaffected) of six families with FNMTC and from 60 controls.
      Quantitative polymerase chain reaction (Q-PCR) and reverse transcription PCR were
      performed to analyze relative telomere length (RTL), gene copy number, and mRNA
      expression of telomerase reverse transcriptase (hTERT), telomere repeat binding
      factor 1 (TRF1), telomere repeat binding factor 2 (TRF2), repressor activator
      protein 1 (RAP1), TRF1 interacting nuclear factor 2 (TIN2), tripeptidyl peptidase
      1 (TPP1), and protection of telomere 1 (POT1). RESULTS: Affected members had
      shorter RTL, as compared with unaffected members (0.98 vs. 1.23, p<0.01). There
      was no significant difference in hTERT, TRF1, TRF2, RAP1, TIN2, TPP1, and POT1
      gene copy number or mRNA expression between affected and unaffected members.
      CONCLUSIONS: RTL is shorter in affected members with FNMTC but is not associated
      with altered copy number or expression in hTERT, TRF1, TRF2, RAP1, TIN2, TPP1,
      and POT1. The small differences in RTL preclude the utility of RTL as a marker
      for FNMTC in at-risk individuals.

PMID- 23009102
TI  - Assessing children's competence to consent in research by a standardized tool: a
      validity study.
AB  - BACKGROUND: Currently over 50% of drugs prescribed to children have not been
      evaluated properly for use in their age group. One key reason why children have
      been excluded from clinical trials is that they are not considered able to
      exercise meaningful autonomy over the decision to participate. Dutch law states
      that competence to consent can be presumed present at the age of 12 and above;
      however, in pediatric practice children's competence is not that clearly
      presented and the transition from assent to active consent is gradual. A gold
      standard for competence assessment in children does not exist. In this article we
      describe a study protocol on the development of a standardized tool for assessing
      competence to consent in research in children and adolescents. METHODS/DESIGN: In
      this study we modified the MacCAT-CR, the best evaluated competence assessment
      tool for adults, for use in children and adolescents. We will administer the tool
      prospectively to a cohort of pediatric patients from 6 to18 years during the
      selection stages of ongoing clinical trials. The outcomes of the MacCAT-CR
      interviews will be compared to a reference standard, established by the judgments
      of clinical investigators, and an expert panel consisting of child psychiatrists,
      child psychologists and medical ethicists. The reliability, criterion-related
      validity and reproducibility of the tool will be determined. As MacCAT-CR is a
      multi-item scale consisting of 13 items, power was justified at 130-190 subjects,
      providing a minimum of 10-15 observations per item. MacCAT-CR outcomes will be
      correlated with age, life experience, IQ, ethnicity, socio-economic status and
      competence judgment of the parent(s). It is anticipated that 160 participants
      will be recruited over 2 years to complete enrollment. DISCUSSION: A validity
      study on an assessment tool of competence to consent is strongly needed in
      research practice, particularly in the child and adolescent population. In this
      study we will establish a reference standard of children's competence to consent,
      combined with validation of an assessment instrument. Results can facilitate
      responsible involvement of children in clinical trials by further development of
      guidelines, health-care policies and legal policies.

PMID- 23009103
TI  - The effect of spinal cord stimulation (SCS) on static balance and gait.
AB  - OBJECTIVES: To investigate whether spinal cord stimulation (SCS) has a negative
      effect on static balance and gait, which is implicated by the increased incidence
      of falls leading to frequently occurring lead migrations. MATERIALS AND METHODS:
      A controlled trial is performed with 11 subjects (four female, seven male) with a
      mean age of 46 years old. A baseline measurement consisting of static balance and
      gait tests was performed. Within two weeks after implantation of a spinal cord
      stimulator, subjects performed the same tests with both stimulation switched on
      and off. Static balance was assessed with eyes open and eyes closed on hard
      surface and foam surface. The velocity of the center of pressure and weight
      symmetry were the main outcome parameters. Kinematics and spatiotemporal outcome
      parameters were used to analyze gait. ANOVAs were used to compare between
      baseline, stimulation on, and stimulation off. RESULTS:  Spinal cord stimulation
      resulted in significant pain relief as scored on a Visual Analog Scale (p <
      0.001). Gait width decreased and this change (indicative of improvement in
      balance) was significant (p = 0.007). No other significant group differences were
      found between stimulation baseline and post-surgery measurements. SCS did not
      influence static balance or gait when group effects were analyzed. Four subjects
      showed significant differences in static balance between stimulation on and off.
      CONCLUSIONS:  The lack of group differences in normal gait and static balance
      cannot explain the increased incidence of falls. However, four subjects showed an
      effect of SCS on static balance. Further research to clarify why only a part of
      the subjects experienced balance problems is recommended and assessments of more
      demanding balance and gait tasks are desirable.

PMID- 23009104
TI  - Enantioselective cyclopropanation of indoles: construction of all-carbon
      quaternary stereocenters.
AB  - The first enantioselective copper-catalyzed cyclopropanation of N-acyl indoles is
      described. Using carbohydrate-based bis(oxazoline) ligands (glucoBox), the
      products were obtained in up to 72% ee. Cyclopropanation of N-Boc 3-methyl indole
      yielded a product with an all-carbon quaternary stereocenter, which is a valuable
      building block for the synthesis of indole alkaloids: Deprotection and
      rearrangement gave a tricyclic hemiaminal ester in 96% ee, which was subsequently
      employed as a key intermediate for the synthesis of (-)-desoxyeseroline.

PMID- 23009105
TI  - Gain studies of 1.3-MUm dilute nitride HELLISH-VCSOA for optical communications.
AB  - The hot electron light emitting and lasing in semiconductor heterostructure
      vertical-cavity semiconductor optical amplifier (HELLISH-VCSOA) device is based
      on Ga0.35In0.65 N0.02As0.08/GaAs material for operation in the 1.3-MUm window of
      the optical communications. The device has undoped distributed Bragg reflectors
      (DBRs). Therefore, problems such as those associated with refractive index
      contrast and current injection, which are common with doped DBRs in conventional
      VCSOAs, are avoided. The gain versus applied electric field curves are measured
      at different wavelengths using a tunable laser as the source signal. The highest
      gain is obtained for the 1.3-MUm wavelength when an electric field in excess of 2
      kV/cm is applied along the layers of the device.

PMID- 23009106
TI  - Morbidity and mortality of diabetic ketoacidosis with and without insulin pump
      care.
AB  - Diabetic ketoacidosis (DKA) is one of the most common, costly, and dangerous
      acute complications in people with type 1 diabetes (T1D). Although DKA has been
      reported to occur with less frequency than severe hypoglycemia, it is associated
      with a higher mortality rate and is the leading cause of diabetes-related deaths
      in children and adolescents. The most common risk factor for DKA is lack of
      adherence to insulin treatment. Other factors include underinsurance, psychiatric
      disorders, occlusion of insulin pump infusion sets, and illness. It has been
      suggested that use of continuous subcutaneous insulin infusion therapy may
      increase the risk for DKA, although clinical trials have not supported this
      claim. Expert care within a T1D specialty clinic may help reduce the risk of DKA
      mortality. Further advances are needed in developing new technologies and methods
      to improve glycemic control in intensively treated patients without increasing
      the risk of acute complications. The purpose of this review is to discuss DKA
      morbidity and mortality in youth with T1D, particularly in relation to insulin
      pump use.

PMID- 23009107
TI  - Re-do aortic operation in a young patient for aggressive Takayasu's arteritis.
AB  - Takayasu's arteritis is an inflammatory arteriopathy which involves the aorta
      and its major branches, causing mainly stenosis of their lumen, though aneurysmal
      lesions can also occur. A young female with Takayasu's disease presented to our
      hospital with acute lung oedema due to severe aortic insufficiency and ascending
      aorta dilatation. She had already undergone distal ascending aorta and hemiarch
      replacement due to Standford type A aortic dissection five years ago. The patient
      had also undergone reconstruction of abdominal arteries' stenoses with
      extraanatomical bypass. We performed a Bentall procedure with a valved conduit
      and implantation of the coronary ostia as buttons on the conduit. A mechanical
      valved graft was used instead of a bioprosthesis, due to possible early
      degradation of a bioprosthesis. The postoperative course was uneventful and the
      one year follow-up was normal. Valve-sparing aortic root replacement should be
      avoided in Takayasu's arteritis due to high rate of recurrent regurgitation.

PMID- 23009108
TI  - TIPE2, a novel biomarker for clinical chronic kidney allograft rejection.
AB  - Tumor necrosis factor-a--induced protein 8-like 2 (TIPE2) has an essential role
      in immune homeostasis, yet the relationship between TIPE2 expression and
      allograft rejection has not been addressed. Dependent on clinical diagnosis, 96
      kidney transplant recipients were divided into three groups, long-term survival
      group, acute rejection group (AR) and chronic rejection group (CR). Thirty-two
      healthy volunteers were used as a control group. The expression of TIPE2 in
      peripheral blood mononuclear cells (PBMC) and kidney biopsy samples was performed
      using reverse transcript-polymerase chain reaction, immunohistochemistry and
      immunofluorescence. The expression of TIPE2 in PBMC of CR group was significantly
      higher than that of the healthy control (P < 0.001), but TIPE2 expression in AR
      group was lower than that of control individuals (P < 0.05). The renal expression
      of TIPE2 in allograft tissue of CR was significantly lower and its expression in
      AR slightly lower than in normal kidneys. The positive correlation between TIPE2
      expression in PBMCs and the CR of allo-kidney grafts indicates that detection of
      TIPE2 in the blood samples may be used as one of the diagnosis molecular markers
      in clinical monitoring kidney chronic rejection.

PMID- 23009110
TI  - Primary biliary cirrhosis: a multi-faced interactive disease involving genetics,
      environment and the immune response.
AB  - Primary biliary cirrhosis (PBC) is considered a model autoimmune disease based on
      several features, including the presence of a highly directed and very specific
      immune response to mitochondrial autoantigens, a female predominance, a targeted
      destruction of the biliary epithelium, and homogeneity between patients. It is
      essentially a chronic progressive cholestatic liver disease characterized by
      immune-mediated destruction of small- and medium-sized intrahepatic bile ducts.
      There is considerable variation in the incidence and prevalence of the disease
      between regions of the world, although such differences likely reflect not only a
      true disparity in disease but also differences in awareness; for example, in the
      United States, PBC is often detected in an asymptomatic stage based on multi
      phasic clinical testing. There has been considerable progress at defining the
      immune response in this disease, including quantitation of autoreactive T cells
      against PDC-E2, the major mitochondrial autoantigen. The overwhelming data
      suggests that patients develop PBC based on a genetic predisposition and loss of
      tolerance to one or more environmental agents. In this review, we will present an
      updated overview of PBC and place it in the context of autoimmunity.

PMID- 23009111
TI  - Expression of Toll-like receptor9 in diffuse large B-cell lymphoma: further
      exploring CpG oligodeoxynucleotide in NFkappaB pathway.
AB  - Human Toll-like receptors (TLRs) that recognize a variety of pathogen-associated
      molecular patterns are associated with activation and immunogenic response in
      lymphoid neoplasms, but rarely explored in diffuse large B-cell lymphoma (DLBCL).
      We conducted this study to evaluate the expression of TLR9 in and potential
      treatment of DLBCL with TLR9 agonist - CpG oligodeoxynucleotide (ODN). The real
      time quantitative reverse transcription-polymerase chain reaction was carried out
      to detect TLR9 expression in 41 formalin-fixed paraffin-embedded samples. The
      transformation of immunophenotype and NFkappaB pathway of DLBCL upon CpG ODN
      stimulation were investigated by a DLBCL cell line. TLR9 was commonly detected in
      DLBCL with relative mRNA levels above 1.0 * 10(-2)  in 35 of 41 cases (85.36%).
      It was suspected that a high proportion of DLBCL to be activated by CpG
      stimulation. In vitro study with a DLBCL cell line revealed an increased CD20,
      but decreased BCL-6 and MUM1/IRF4 expression after treatment with CpG ODN. The
      NFkappaB pathway was initially activated, but finally suppressed upon CpG ODN
      stimulation. The proliferation of tumor cells was also inhibited by long time
      incubation. These findings provide new insights into the role of TLR9 in DLBCL
      and potential implication of TLR9 agonist in the treatment of DLBCL.

PMID- 23009112
TI  - TP53  mutations in astrocytic gliomas: an association with histological grade,
      TP53  codon 72 polymorphism and p53 expression.
AB  - TP53 mutations and polymorphisms have been widely related to many cancers as long
      as these alterations may impair its capacity to induce cell cycle arrest, DNA
      repair mechanisms, and apoptosis. Although TP53 alterations have been studied in
      astrocytic tumors, there is a lack of analysis considering specific TP53
      mutations and their associations with p53 immunostainning, polymorphisms and
      their significance among the histological grades. Thus, we analyzed TP53
      alterations in exons 2-11, including the codon 72 polymorphism, using DNA
      sequencing in 96 astrocytic gliomas (18 grade I, 20 grade II, 14 grade III, and
      44 grade IV). Also, immunohistochemistry was assessed to evaluate the p53 protein
      expression. In this study, we found that the higher histological grades were
      statistically associated with TP53 mutations. Some of these mutations, such as
      TP53 P98T and TP53 G244S, seemed to be a specific marker for the higher grades,
      and the TP53 E286K mutation appears to be a World Health Organization grade III
      IV progression marker. Also, the TP53 P98T mutation, in exon 4, is very likely to
      be important on the stabilization of the p53 protein, leading to its
      immunopositivity and it is potentially associated with the TP53 72Pro/Pro
      genotype.

PMID- 23009113
TI  - Altered expression of p27(Kip1) -interacting cell-cycle regulators in the adult
      testicular germ cell tumors: potential role in tumor development and histological
      progression.
AB  - We examined the potential role of cell-cycle dysregulation in the development and
      histological progression of adult testicular germ cell tumors (TGCTs).
      Expressions of p27(Kip1) -interacting cell-cycle regulators (down-regulation of
      p27(Kip1)  and overexpression of Skp2, Cks1, cyclin A, and cyclin E) and Ki-67
      labeling index (LI) were immunohistochemically examined in histological
      components of 50 intratubular germ cell neoplasms, unclassified (IGCNUs); 74
      seminomas; and 25 embryonal carcinomas, identified from 88 patients. Altered
      expression of p27(Kip1) , Skp2, Cks1, cyclin A, and cyclin E was observed in 20%,
      12%, 16%, 10%, and 24% of IGCNUs; 26%, 36%, 27%, 89%, and 23% of seminomas; and
      48%, 68%, 56%, 100%, and 60% of embryonal carcinomas, respectively. A significant
      difference in the frequency of Skp2 and cyclin A overexpression was observed
      between IGCNUs and seminomas. Significantly more frequent alterations of Skp2,
      Cks1, and cyclin E and p27(Kip1)  were detected in embryonal carcinomas than in
      seminomas. Alterations of all cell-cycle regulators were significantly more
      frequent in embryonal carcinomas than in IGCNUs. The mean Ki-67 LI significantly
      increased from IGCNU (21.2%) through seminoma (34.7%) to embryonal carcinoma
      (54.2%). These results suggest that alterations of the p27(Kip1) -interacting
      cell-cycle regulators are common in TGCTs and may be involved in their
      histological progression.

PMID- 23009114
TI  - Intratumoral T but not B lymphocytes are related to clinical outcome in prostate
      cancer.
AB  - The number of tumor-infiltrating lymphocytes is functionally important and
      correlates with clinical outcome in several tumor entities. Herein we explore the
      impact of the density of T and B lymphocytes in prostate cancer tissue on
      prostate-specific antigen (PSA) recurrence after prostatectomy in 3261 prostate
      cancer tissue samples. The number of prostate cancer-infiltrating CD3-positive T
      cells and CD20-positive B cells per tissue spot in a tissue microarray format was
      determined by immunohistochemistry and was correlated with clinical and
      pathological data from the same patient cohort. Patients with very low and very
      high numbers of CD3-positive T cells per tissue spot had a significantly shorter
      PSA recurrence-free survival compared to patients with intermediate numbers of T
      cells (p = 0.0188). Furthermore, a high number of CD3-positive T cells per tissue
      spot was associated with fusion type prostate cancer identified by ERG expression
      analysis. The number of CD20-positive B cells per tissue spot was not associated
      with other clinical and histopathological parameters. This study indicates that
      the density of T but not B cells plays a functional role in the biology of
      prostate cancer and may have an impact on clinical outcome in this frequent
      neoplasia.

PMID- 23009115
TI  - The use of sequential organ failure assessment parameters in an awake porcine
      model of severe Staphylococcus aureus sepsis.
AB  - The human sequential organ failure assessment (SOFA) scoring system is used
      worldwide in intensive care units for assessing the extent of organ
      dysfunction/failure in patients with severe sepsis. An increasing number of
      septic cases are caused by Gram-positive bacteria as Staphylococcus aureus. The
      aim of the current study was to apply the human SOFA parameters in an awake,
      porcine model of severe S. aureus sepsis. Five pigs were inoculated intravenously
      with S. aureus and two control animals were sham-inoculated. Extensive clinical
      monitoring and sequential blood sampling was obtained and analysed for SOFA
      parameters. Dysfunction/failure was observed in the respiratory, haemostatic and
      hepatic system of all infected animals, together with initial cardiovascular
      dysfunction. The pulmonary system was the first to fail clinically, which
      corresponds with similar human findings, whereas the liver was affected earlier
      in pigs compared to humans. The use of human SOFA parameters was valuable in
      identifying dysfunctional/failing organs and showed consistency between this
      porcine model and human severe sepsis. Applying SOFA parameters in this model
      increased the relevance for comparison to clinical methods of evaluating human
      severe sepsis. Changes in SOFA parameters may in future porcine studies serve as
      a target for monitoring the effect of therapeutic intervention.

PMID- 23009116
TI  - No link between rosacea and Propionibacterium acnes.
AB  - Rosacea is a common skin disease in adults affecting mainly the facial skin.
      Although inflammation appears to play a pathogenic role in rosacea, initiating
      factors are largely unknown. Microbial involvement in the development of rosacea
      has been suggested previously. We aimed to visualize Propionibacterium acnes in
      the skin compartments of rosacea patients. Facial skin biopsies from 82 rosacea
      patients and 25 controls were stained with a P. acnes-specific monoclonal
      antibody (QUBPa3). Seven of 82 patients (8.5%) tested positive for P. acnes which
      was present either as a biofilm (57% of positive) or a microcolony (43%) in
      colonized patients. Our results suggest that P. acnes does not play a major role
      in the pathogenesis of rosacea.

PMID- 23009117
TI  - Antibiotic resistance and molecular epidemiology of the beta-lactamase-producing
      Haemophilus influenzae isolated in Chongqing, China.
AB  - This study aimed to determine the antibiotic resistance and molecular
      epidemiology of Haemophilus influenzae isolated from children with acute
      respiratory infection in Chongqing, China. To this end, 1967 H. influenzae
      isolates from 2006 to 2009 were analysed regarding beta-lactamase production and
      antibiotic resistance. Ninety-nine beta-lactamase-producing H. influenzae
      isolates from 2010 were analysed for antibiotic resistance and promoter regions
      of bla(TEM) (-1) . beta-lactamase production was found in 35.8% (705/1967) of the
      strains. All ninety-nine beta-lactamase-producing strains from 2010 were of the
      TEM-1 type as determined by PCR but did not produce the predicted 1075 bp
      product. According to PCR-SSCP and DNA sequencing, the promoter regions of
      bla(TEM) (-1) were categorized into 6 genotypes as SSCP1 (Pdel), SSCP2 (Pa/Pb),
      SSCP3 (P4), SSCP4 (Prpt.b), SSCP5 (2Prpt) and SSCP6 (P3.b). The Pdel, Pa/Pb and
      Prpt.b were common promoters of bla(TEM) (-1) for H. influenzae isolated from
      children in Chongqing. Strains with Prpt.b were more resistant to ampicillin
      (AMP) than strains with Pdel, Pa/Pb and P4 (p < 0.05). Therefore, bla(TEM-1) beta
      lactamase is the main mechanism for resistance of H. influenzae to ampicillin in
      Chongqing. Furthermore, the Prpt.b promoters may be related to the high
      resistance of H. influenzae to AMP.

PMID- 23009118
TI  - Serologic response to a 23-valent pneumococcal vaccine administered prior to
      autologous stem cell transplantation in patients with multiple myeloma.
AB  - Patients with multiple myeloma are known to have an increased risk of infections
      with Streptococcus pneumoniae and vaccination is recommended. We retrospectively
      investigated the response of a 23-valent polysaccharide-based pneumococcal
      vaccine in 60 patients with multiple myeloma administered prior to autologous
      stem cell transplantation (ASCT). Specific antibody titers were measured before
      and after vaccination. Disease stage was evaluated and associated to the
      response. We found that 33% of the patients responded to the vaccine. There was a
      statistic significant association between response to the vaccine and disease
      stage (p = 0.01). We conclude that vaccination against S. pneumoniae prior to
      ASCT is reasonable at least in patients responding well to induction therapy, but
      still it is important to be aware that the response is frequently poor and the
      duration of it is unknown.

PMID- 23009119
TI  - Length-dependent change of optical, magnetic, and vibrational properties of
      vanadate (V(IV)O3(2-)) quantum wire embedded in AM-6 vanadosilicate.
AB  - AM-6 and VSH-1 are vanadosilicates containing VO(3)(2-) quantum wires and
      oxovanadate [O?VO(4)](2-) quantum dots, respectively. We developed methods to
      synthesize pure, highly crystalline, monodisperse, and all-V(IV) AM-6 and VSH-1
      crystals with sizes between 0.2-0.3 and 10 MUm. On the basis of their optical,
      magnetic susceptibility, vibrational, and electron spin resonance (ESR)
      properties, we have elucidated the following interesting phenomena. The length of
      the VO(3)(2-) quantum wire (l) linearly increases as the length along the [110]
      direction {L([110])} increases. The band gap energy (E(g)) of the VO(3)(2-)
      quantum wire progressively decreases with increasing l even when it reaches ~210
      nm, indicating that the Bohr length (the length at which the quantum confinement
      effect no longer appears) is longer than 200 nm. The deduced MU(z) and MU(xy) are
      0.0005m(e) and 15.7m(e), respectively. Per-V(IV)-ion oscillator strength of the d
      d transition increases by 7-9 times and that of CT transition increases by 1.5
      1.9 times with increasing l from ~50 to 210 nm (by ~4 times). The longitudinal
      vibration frequency nu of the VO(3)(2-) quantum wire decreases and the intensity
      of the vibrational band increases as l increases. The ESR intensity increases
      while the peak-to-peak width decreases as l increases, indicating that the spin
      spin relaxation rate (R(ssr)) decreases as l increases. The magnetic
      susceptibility chi decreases as l increases, especially at T > 125 K, indicating
      that the tendency of the d(1) electron spins to orient to the external magnetic
      field decreases with increasing l.

PMID- 23009120
TI  - Development of the Pediatric Quality of Life InventoryTM Eosinophilic Esophagitis
      module items: qualitative methods.
AB  - BACKGROUND: Currently there is no disease-specific outcome measure to assess the
      health-related quality of life (HRQOL) of pediatric patients with Eosinophilic
      Esophagitis (EoE). Therefore, the objective of this qualitative study was to
      further develop and finalize the items and support the content validity for the
      new Pediatric Quality of Life InventoryTM (PedsQLTM) Eosinophilic Esophagitis
      Module. METHODS: Multiphase qualitative methodology was utilized in the
      development of the PedsQLTM EoE Module conceptual model. Focus interview
      transcripts of pediatric patients with EoE and their parents and expert review
      were previously used to develop the initial items and domains for the PedsQLTM
      EoE Module. In the current investigation, utilizing the respondent debriefing
      methodology, cognitive interviewing was conducted individually with pediatric
      patients with EoE and their parents on each newly developed item. RESULTS:
      Information from a total of 86 participants was obtained in combination from the
      previous investigation and the current study. From the previous 42 focus
      interviews, items were developed around the domain themes of symptoms,
      difficulties with eating food, treatment adherence, worry about symptoms and
      illness, feelings of being different than family and peers, and problems
      discussing EoE with others. In the current study's cognitive interviewing phase,
      a separate cohort of 44 participants systematically reviewed and provided
      feedback on each item. Items were added, modified or deleted based on this
      feedback. Items were finalized after this feedback from patients and parents.
      CONCLUSIONS: Using well-established qualitative methods, the content validity of
      the new PedsQLTM Eosinophilic Esophagitis Module items was supported in the
      current investigation. In the next iterative instrument development phase, the
      PedsQLTM Eosinophilic Esophagitis Module is now undergoing multisite national
      field testing.

PMID- 23009121
TI  - Role of boundary layer diffusion in vapor deposition growth of chalcogenide
      nanosheets: the case of GeS.
AB  - We report a synthesis of single-crystalline two-dimensional GeS nanosheets using
      vapor deposition processes and show that the growth behavior of the nanosheet is
      substantially different from those of other nanomaterials and thin films grown by
      vapor depositions. The nanosheet growth is subject to strong influences of the
      diffusion of source materials through the boundary layer of gas flows. This
      boundary layer diffusion is found to be the rate-determining step of the growth
      under typical experimental conditions, evidenced by a substantial dependence of
      the nanosheet's size on diffusion fluxes. We also find that high-quality GeS
      nanosheets can grow only in the diffusion-limited regime, as the crystalline
      quality substantially deteriorates when the rate-determining step is changed away
      from the boundary layer diffusion. We establish a simple model to analyze the
      diffusion dynamics in experiments. Our analysis uncovers an intuitive correlation
      of diffusion flux with the partial pressure of source materials, the flow rate of
      carrier gas, and the total pressure in the synthetic setup. The observed
      significant role of boundary layer diffusions in the growth is unique for
      nanosheets. It may be correlated with the high growth rate of GeS nanosheets, ~3
      5 MUm/min, which is 1 order of magnitude higher than other nanomaterials (such as
      nanowires) and thin films. This fundamental understanding of the effect of
      boundary layer diffusions may generally apply to other chalcogenide nanosheets
      that can grow rapidly. It can provide useful guidance for the development of
      general paradigms to control the synthesis of nanosheets.

PMID- 23009123
TI  - Attractive and repulsive interactions originating from lateral nanometer
      variations in surface charge/energy of hyaluronic acid and chondroitin sulfate
      doped polypyrrole observed using atomic force microscopy.
AB  - Phase imaging in atomic force microscopy (AFM) is a useful technique for
      determining dissipative tip-sample interactions related to changes in the
      material surface properties such as local stiffness or adhesion. In this work, we
      applied both phase imaging and phase spectroscopy measurements to conducting
      polymer (polypyrrole) doped with either hyaluronic acid or chondroitin sulfate.
      As observed in previous studies, phase-separated regions correlating with the
      characteristic nodular topography of polypyrrole and attributed to crystalline
      (doped) and amorphous (undoped) regions were observed. However, through
      additional phase spectroscopy measurements, we show that the phase-separated
      regions can arise due to variation in attractive and repulsive tip-sample
      interactions across the polymer surface. We show that these attractive and
      repulsive interactions are dependent on the redox state and degree of doping and
      suggest that they are related to phase separation of the polymer surface charge
      and/or energy. The latter may have implications for these materials when under
      investigation in a fluid, or biological, environment. For example, such surface
      variations will play a role in electrostatic forces, which in turn can influence
      protein and cellular interactions.

PMID- 23009124
TI  - Rare case of optic fracture in a glass intraocular lens after neodymium-doped
      yttrium aluminium garnet capsulotomy.

PMID- 23009122
TI  - Novel NMDA receptor modulators: an update.
AB  - INTRODUCTION: The NMDA receptor is a ligand-gated ion channel that plays a
      critical role in higher level brain processes and has been implicated in a range
      of neurological and psychiatric conditions. Although initial studies for the use
      of NMDA receptor antagonists in neuroprotection were unsuccessful, more recently,
      NMDA receptor antagonists have shown clinical promise in other indications such
      as Alzheimer's disease, Parkinson's disease, pain and depression. Based on the
      clinical observations and more recent insights into receptor pharmacology, new
      modulatory approaches are beginning to emerge, with potential therapeutic
      benefit. AREAS COVERED: The article covers the known pharmacology and important
      features regarding NMDA receptors and their function. A discussion of pre
      clinical and clinical relevance is included, as well. The subsequent patent
      literature review highlights the current state of the art targeting the receptor
      since the last review in 2010. EXPERT OPINION: The complex nature of the NMDA
      receptor structure and function is becoming better understood. As knowledge about
      this receptor increases, it opens up new opportunities for targeting the receptor
      for many therapeutic indications. New strategies and advances in older
      technologies will need to be further developed before clinical success can be
      achieved. First-in-class potentiators and subunit-selective agents form the basis
      for most new strategies, complemented by efforts to limit off-target liability
      and fine-tune on-target properties.

PMID- 23009125
TI  - Body site matters: an evaluation and application of a novel histological
      methodology on the quantification of mucous cells in the skin of Atlantic salmon,
      Salmo salar L.
AB  - Mucous cell size and distribution were investigated in the skin of five salmon
      using a novel stereology-based methodology: one (48 cm) fish to test 15 tissue
      treatment combinations on measures of cell area and density on the dorsolateral
      region and, using the most suitable treatment, we mapped mucous cell differences
      between body regions on four (52 cm) salmon, comprising a male and a female on
      each of two diets. The section site, decalcification, embedding medium and plane
      of sectioning all impacted significantly on mucous cell size, whereas mucous cell
      density is more robust. There were highly significant differences in both mucosal
      density and mean mucous cell size depending on body site: the dorsolateral skin
      of the four salmon had significantly denser (about 8% of skin area) and larger
      (mean about 160 MUm(2)) mucous cells, whereas the lowest mean density (about 4%)
      and smallest mean area (115 MUm(2)) were found on the head. We found that 100
      random measurements may be sufficient to distinguish differences >7 MUm(2) in
      mean mucous cell areas. The results further suggest that salmon exhibit a dynamic
      repeatable pattern of mucous cell development influenced by sex, diet and
      possibly strain and season.

PMID- 23009126
TI  - The Beijing version of the Montreal Cognitive Assessment as a brief screening
      tool for mild cognitive impairment: a community-based study.
AB  - BACKGROUND: A cross-sectional validation study was conducted in several urban and
      rural communities in Beijing, China, to evaluate the effectiveness of the Beijing
      version of the Montreal Cognitive Assessment (MoCA-BJ) as a screening tool to
      detect mild cognitive impairment (MCI) among Chinese older adults. METHODS: The
      MoCA-BJ and the Mini-Mental State Examination (MMSE) were administered to 1001
      Chinese elderly community dwellers recruited from three different regions (i.e.,
      newly developed, old down-town, and rural areas) in Beijing. Twenty-one of these
      participants were diagnosed by experienced psychiatrists as having dementia, 115
      participants were diagnosed as MCI, and 865 participants were considered to be
      cognitively normal. To analyze the effectiveness of the MoCA-BJ, we examined its
      psychometric properties, conducted item analyses, evaluated the sensitivity and
      specificity of the scale, and compared the scale with the MMSE. Demographic and
      regional differences among our subjects were also taken into consideration.
      RESULTS: Under the recommended cut-off score of 26, the MoCA-BJ demonstrated an
      excellent sensitivity of 90.4%, and a fair specificity (31.3%). The MoCA-BJ
      showed optimal sensitivity (68.7%) and specificity (63.9%) when the cut-off score
      was lowered to 22. Among all the seven cognitive sub-domains, delayed recall was
      shown to be the best index to differentiate MCI from the normal controls.
      Regional differences disappeared when the confounding demographic variables
      (i.e., age and education) were controlled. Item analysis showed that the internal
      consistency was relatively low in both naming and sentence repetition tasks, and
      the diagnostic accuracy was similar between the MoCA-BJ and the MMSE.
      CONCLUSIONS: In general, the MoCA-BJ is an acceptable tool for MCI screening in
      both urban and rural regions of Beijing. However, presumably due to the
      linguistic and cultural differences between the original English version and the
      Chinese version of the scale, and the lower education level of Chinese older
      adults, the MoCA-BJ is not much better than the MMSE in detecting MCI, at least
      for this study sample. Further modifications to several test items of the MoCA-BJ
      are recommended in order to improve the applicability and effectiveness of the
      MoCA-BJ in MCI screening among the Chinese population.

PMID- 23009127
TI  - The rationale of patients with early-stage papillary thyroid cancer for accepting
      or rejecting radioactive iodine remnant ablation.

PMID- 23009128
TI  - ICF and casemix models for healthcare funding: use of the WHO family of
      classifications to improve casemix.
AB  - PURPOSE: Casemix models for funding activity in health care and assessing
      performance depend on data based on uniformity of resource utilisation. It has
      long been an ideal to relate the measure of value more to patient outcome than
      output. A problem frequently expressed by clinicians is that measures of activity
      such as Functional Independence Measure (FIM) and Barthel Index scores may not
      sufficiently represent the aspirations of patients in many care programs. METHOD:
      Firstly, the key features of the International Classification of Functioning,
      Disability and Health are outlined. Secondly, the use of ICF dimensions in
      Australia and other countries is reviewed. Thirdly, a broader set of domains with
      potential for casemix funding models and performance reporting is considered.
      RESULTS: In recent years, the ICF has provided a more developed set of domains
      against which outcome goals can be expressed. Additional dimensions could be used
      to supplement existing data. Instances of developments in this area are
      identified and their potential discussed. CONCLUSIONS: A well-selected set of
      data items representing the broader dimensions of outcome goals may provide the
      ability to more meaningfully and systematically measure the goals of both
      curative and rehabilitation care against which outcome should be measured. More
      information about patient goals may be needed.

PMID- 23009129
TI  - The movement characteristics of English Premiership rugby union players.
AB  - The purpose of this investigation was to quantify the movement characteristics of
      elite rugby union players during competitive play and identify whether position
      related differences exist. Ninety-eight elite players from eight English
      Premiership Clubs were tracked using global positioning systems (GPS) during 44
      competitive matches throughout the 2010/2011 season. Player positions were
      defined as: (1) backs or forwards; (2) front, second and back rows, scrum half,
      inside and outside backs; (3) 15 individual positions (numbers 1-15). Analysis
      revealed the game is predominantly played at low speeds with little distance
      covered 'sprinting' by either the backs (50 +/- 76 m) or the forwards (37 +/- 64
      m). The backs travelled greater (P < 0.05) absolute and relative distances than
      the forwards. The scrum half covered the greatest total distance during a match
      (7098 +/- 778 m) and the front row the least (5158 +/- 200 m). The back row
      covered the greatest distances at 'sprinting' speeds, particularly the number 8
      position (77 m). These findings reflect notable differences in the movement
      characteristics displayed by elite rugby union players in specific positional
      roles, and reinforce the contemporary view that training programmes for such
      players ought to be structured with this in mind.

PMID- 23009130
TI  - Survivors of torture: prevalence in an urban emergency department.
AB  - OBJECTIVES: Torture has been documented in 132 countries, and approximately
      400,000 survivors of torture reside in the United States. It is unknown if
      torture survivors seek medical care in emergency departments (EDs). The authors
      set out to estimate the prevalence of survivors of torture presenting to an urban
      ED. METHODS: A cross-sectional survey of ED patients was performed by convenience
      sampling from October 2008 to September 2009 in a large urban teaching hospital
      in New York City. ED patients not of a vulnerable population were consented and
      entered into the study. Participants were asked two screening questions to
      ascertain if they were self-reported survivors of torture. For exploratory
      purposes only, these individuals were further queried about their experiences.
      The detailed responses of these self-reported survivors of torture were compared
      to the United Nations Convention Against Torture (UNCAT) definition by a blinded,
      independent panel. RESULTS: Of 470 study participants, 54 individuals (11.5%, 95%
      confidence interval [CI] = 8.6% to 14.4%) self-reported torture. Nine (16.7%) had
      ongoing physical disabilities, 30 (55.6%) had recurrent intrusive and distressing
      memories, 42 (77.8%) never had a physician inquire about torture, and only eight
      (14.8%) had requested political asylum. Of these self-reported survivors of
      torture, 29 (53.7%) met the UNCAT definition, for an adjudicated prevalence of
      6.2% (95% CI = 4.3% to 8.7%). CONCLUSIONS: Self-reported survivors of torture
      presented to this urban ED, and a significant proportion of them met the UNCAT
      definition of a torture survivor. Continuing torture-related medical and
      psychological sequelae were identified, yet there was a low rate of asylum
      seeking. Only a minority were previously identified by a physician. These data
      suggest an unrecognized public health concern and an opportunity for emergency
      physicians to intervene and refer survivors of torture to existing community
      resources.

PMID- 23009131
TI  - Adsorption of self-assembled rigid rods on two-dimensional lattices.
AB  - Monte Carlo (MC) simulations have been carried out to study the adsorption on
      square and triangular lattices of particles with two bonding sites that, by
      decreasing temperature or increasing density, polymerize reversibly into chains
      with a discrete number of allowed directions and, at the same time, undergo a
      continuous isotropic-nematic (IN) transition. The process has been monitored by
      following the behavior of the adsorption isotherms (chemical potential MU as a
      function of the surface coverage theta) for different values of lateral
      interaction energy/temperature. The numerical data were compared with mean-field
      analytical predictions and exact functions for noninteracting and 1D systems. The
      obtained results revealed the existence of three adsorption regimes in
      temperature. (1) At high temperatures, above the critical one characterizing the
      IN transition at full coverage T(c)(theta = 1), the particles are distributed at
      random on the surface and the adlayer behaves as a noninteracting 2D system. (2)
      At very low temperatures, the asymmetric monomers adsorb, forming chains over
      almost the entire range of coverage, and the adsorption process behaves as a 1D
      problem. (3) In the intermediate regime, the system exhibits a mixed regime and
      the filling of the lattice proceeds according to two different processes. In the
      first stage, the monomers adsorb isotropically on the lattice until the IN
      transition occurs in the system and, from this point, particles adsorb, forming
      chains so that the adlayer behaves as a 1D fluid. The two adsorption processes
      are present in the adsorption isotherms, and a marked singularity can be observed
      that separates both regimes. Thus, the adsorption isotherms appear as sensitive
      quantities with respect to the IN phase transition, allowing us (i) to reproduce
      the phase diagram of the system for square lattices and (ii) to obtain an
      accurate determination of the phase diagram for triangular lattices.

PMID- 23009132
TI  - Spinal cord stimulation for intractable pain following limb amputation.
AB  - OBJECTIVE: ?? Spinal cord stimulation (SCS) by high-frequency electrical pulses
      has been used since the early 1970s for relief of chronic intractable pain
      following limb amputation. The long-??term effectiveness of SCS for amputation
      ??related pain with ongoing after-care is reviewed by assessment of all such
      cases managed over 20 years in the Neurostimulator Clinic at the Royal London
      Hospital. MATERIALS AND METHODS: ?? Twelve amputation-??related pain patients had
      quadripolar paddle electrodes (Resume; Medtronic Inc., Minneapolis, MN, USA)
      inserted epidurally by laminectomy over the thoracic or cervical dorsal spinal
      cord and connected to remotely controlled subcutaneously implanted stimulators
      (Itrel2, Itrel3, Synergy; Medtronic). RESULTS: ?? Two of 12 patients had
      unsuccessful stimulation, one despite repeated electrode revisions. Two were
      subsequently lost to follow-??up, one had delayed spontaneous resolution of
      phantom limb pain, one had a technical fault, and one had gradually waning
      benefit over 19 years. In the remaining five patients having ongoing follow-up,
      self-??reported initial and final magnitudes of pain relief were unchanged, with
      a mean (SD) of 66% (18.2%). Benefits calculated from local and general visual
      analogue pain scores were similarly unchanged (initial local 48.8% [18.7%]; final
      local 50.0% [17.6%]; initial general 60.8% [10.9%]; final general 57.9% [12.3%]).
      Continued successful stimulation often required frequent changes of stimulating
      electrode contacts. Revision procedures for technical problems or pain at the
      battery site were universally successful. CONCLUSIONS: ?? Successful SCS in some
      patients with amputation-??related pain otherwise resistant to treatment
      indicates that the procedure merits continued use with further efforts to refine
      technique.

PMID- 23009133
TI  - Species diversity and biting activity of Anopheles dirus and Anopheles baimaii
      (Diptera: Culicidae) in a malaria prone area of western Thailand.
AB  - BACKGROUND: A survey of adult anopheline mosquito diversities, collected from
      September 2009 to August 2010, was conducted in a malaria endemic area of western
      Thailand. Two anopheline species complexes, Dirus and Minimus, along with the
      Maculatus group were observed. Of several species documented from within each
      complex and group, four important malaria vectors were identified, including An.
      dirus, An. baimaii, An. minimus, and An. sawadwongporni. Information on biting
      activity and host preference for any single species within the Dirus complex has
      never been assessed. Using specific molecular identification assays, the trophic
      behavior and biting activity of each sibling species within the Dirus complex
      were observed and analyzed for the Kanchanaburi Province, Thailand. METHODS:
      Adult female mosquitoes were collected for two consecutive nights each month
      during a one year period. Three collection methods, human landing indoor (HLI),
      human landing outdoor (HLO), and cattle baited collections (CBC) were applied.
      Each team of collectors captured mosquitoes between 1800 and 0600 h. RESULTS:
      From a total of 9,824 specimens, 656 belong to the Dirus complex (An. dirus 6.09%
      and An. baimaii 0.59%), 8,802 to the Minimus complex (An. minimus 4.95% and An.
      harrisoni 84.65%) and 366 to the Maculatus group (An. maculatus 2.43% and An.
      sawadwongporni 1.29%). Both An. dirus and An. baimaii demonstrated exophagic and
      zoophilic behaviors. Significantly greater numbers of An. dirus and An. baimaii
      were collected from cattle as compared to humans (P = 0.003 for An. dirus and P =
      0.048 for An. baimaii). CONCLUSIONS: Significantly greater numbers of An. dirus
      and An. baimaii were collected from cattle baited traps as compared to human
      landing collections (P < 0.05), demonstrating that both species show a strong
      zoophilic behavior. Knowledge of host-seeking behavior helps to define a species'
      capacity to acquire and transmit malaria and its contribution to the overall risk
      for disease transmission in the human population, as well as, assisting in the
      design and implementation of appropriate vector prevention and control
      strategies.

PMID- 23009134
TI  - The AJT Report: news and issues that affect organ and tissue transplantation.
AB  - In a climate of mainstream media stories touting the latest discoveries in
      regenerative medicine and claims from what are sometimes referred to as "stem
      cell clinics," this month "The AJT Report" takes a look at how regenerative
      medicine fits into the field of transplantation, and how we might balance the
      competing forces of science and fiction.

PMID- 23009135
TI  - Literature Watch: implications for transplantation.

PMID- 23009136
TI  - The graying of organ transplantation.

PMID- 23009137
TI  - A novel definition of cardiac allograft vasculopathy.

PMID- 23009138
TI  - Is the time ripe for genomic diagnosis and prediction of rejection?

PMID- 23009140
TI  - Successful emergent lung transplantation after remote ex vivo perfusion
      optimization and transportation of donor lungs.
AB  - A recent clinical trial provided evidence that ex vivo lung perfusion (EVLP)
      results in optimized human donor lungs for transplantation. Excellent recipient
      outcomes were documented after 4 h of normothermic perfusion. We report a
      clinical case utilizing remote EVLP to assess and improve function of initially
      otherwise unacceptable injured donor lungs followed by transportation and
      subsequent bilateral lung transplantation in a patient with virally induced
      refractory respiratory failure supported with extracorporeal membrane
      oxygenation. This is the first lung transplantation with the application of
      remote EVLP, wherein the donor lungs were transported from the donor hospital to
      a center for EVLP and then transported to another hospital for transplantation.
      It is also the first case of lung transplantation in the United States utilizing
      EVLP for functional optimization leading to successful transplantation. Organ
      procurement data, EVLP assessment, and the pre- and postoperative course of the
      recipient are presented. The available evidence supporting EVLP, the humanitarian
      and cooperative utilization of lungs otherwise discarded, are discussed.

PMID- 23009139
TI  - A peripheral blood diagnostic test for acute rejection in renal transplantation.
AB  - Monitoring of renal graft status through peripheral blood (PB) rather than
      invasive biopsy is important as it will lessen the risk of infection and other
      stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker
      panels were discovered by microarrays at a single center and subsequently
      validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12
      US pediatric transplant programs. A total of 367 unique human PB samples, each
      paired with a graft biopsy for centralized, blinded phenotype classification,
      were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft
      injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a
      five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high
      accuracy. A logistic regression model was built on independent training-set (n =
      47) and validated on independent test-set (n = 198)samples, discriminating AR
      from STA with 91% sensitivity and 94% specificity and AR from all other non-AR
      phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose
      AR potentially avoiding the need for invasive renal biopsy. These data support
      the conduct of a prospective study to validate the clinical predictive utility of
      this diagnostic tool.

PMID- 23009142
TI  - Biliary leak with tardus parvus arterial waveform after liver transplantation.

PMID- 23009143
TI  - Reasons for breakthrough CMV disease in patients who receive preemptive therapy.

PMID- 23009144
TI  - Response to letter regarding "cytomegalovirus replication kinetics in solid organ
      transplant recipients managed by preemptive therapy".

PMID- 23009146
TI  - Detection of nerve agent stimulants based on photoluminescent porous silicon
      interferometer.
AB  - Porous silicon (PSi) exhibiting dual optical properties, both Fabry-Perot fringe
      and photolumincence, was developed and used as chemical sensors. PSi samples were
      prepared by an electrochemical etch of p-type silicon under the illumination of
      300-W tungsten lamp during the etch process. The surface of PSi was characterized
      by cold field-emission scanning electron microscope. PSi samples exhibited a
      strong visible orange photoluminescence at 610 nm with an excitation wavelength
      of 460 nm as well as Fabry-Perot fringe with a tungsten light source. Both
      reflectivity and photoluminescence were simultaneously measured under the
      exposure of organophosphate vapors. An increase of optical thickness and
      quenching photoluminescences under the exposure of various organophosphate vapors
      were observed.

PMID- 23009147
TI  - Clinical use of ventricular assist devices as destination therapy for obese
      patients: what remains unanswered?

PMID- 23009148
TI  - Super-resolution fluorescence quenching microscopy of graphene.
AB  - Lately, fluorescence quenching microscopy (FQM) has been introduced as a new tool
      to visualize graphene-based sheets. Even though quenching of the emission from a
      dye molecule by fluorescence resonance energy transfer (FRET) to graphene happens
      on the nanometer scale, the resolution of FQM so far is still limited to several
      hundreds of nanometers due to the Abbe limit restricting the resolution of
      conventional light microscopy. In this work, we demonstrate an advancement of FQM
      by using a super-resolution imaging technique for detecting fluorescence of color
      centers used in FQM. The technique is similar to stimulated emission depletion
      microscopy (STED). The combined "FRET+STED" technique introduced here for the
      first time represents a substantial improvement to FQM since it exhibits in
      principle unlimited resolution while still using light in the visible spectral
      range. In the present case we demonstrate all-optical imaging of graphene with
      resolution below 30 nm. The performance of the technique in terms of imaging
      resolution and contrast is well described by a theoretical model taking into
      account the general distance dependence of the FRET process and the distance
      distribution of donor centers with respect to the flake. In addition, the change
      in lifetime for partially quenched emitters allows extracting the quenching
      distance from experimental data for the first time.

PMID- 23009150
TI  - First total synthesis of epicoccarine A via O- to C-acyl rearrangement strategy.
AB  - The first total synthesis of antibacterial epicoccarine A isolated from a fungus
      Epicoccum sp. has been accomplished in 10 steps along with synthetic elaboration
      of its C5-epimer, highlighting the utility of O- to C-acyl rearrangement of a 4-O
      acyltetramic acid derivative. Comparison of spectroscopic properties and specific
      optical rotations of the synthetic samples with those reported for authentic
      material has clearly indicated the unspecified absolute stereochemistry of this
      natural product to be 5S.

PMID- 23009149
TI  - A pilot randomized controlled trial to improve geriatric frailty.
AB  - BACKGROUND: Few randomized controlled trials (RCTs) report interventions
      targeting improvement of frailty status as an outcome. METHODS: This RCT enrolled
      117 older adults (65-79 years of age) in Toufen, Taiwan who scored 3-6 on The
      Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone
      Version and then score >=1 on the Cardiovascular Health Study Phenotypic
      Classification of Frailty (CHS_PCF). With a two by two factorial design, subjects
      were randomly assigned to interventions (Exercise and nutrition, EN, n = 55 or
      problem solving therapy, PST, n = 57) or controls (non-EN, n = 62 or non-PST, n =
      60). Educational booklets were provided to all. EN group subjects received
      nutrition consultation and a thrice-weekly exercise-training program while PST
      group subjects received 6 sessions in 3 month. Subjects were followed at 3, 6,
      and 12 months. Primary outcome was improvement of the CHS_PCF by at least one
      category (from pre-frail to robust, or from frail to pre-frail or robust) from
      baseline assessments. One hundred and one completed final assessments. Intention
      to-treat analysis with the generalized estimating equation model was applied with
      adjustment for time and treatment-by-time interactions. RESULTS: Mean age was
      71.4 +/- 3.7 years, with 59% females. Baseline characteristic were generally
      comparable between groups. EN group subjects had a higher improvement rate on the
      primary outcome than non-EN group subjects (45% vs 27%, adjusted p = 0.008) at 3
      months, but not 6 or 12 months. They also had more increase of serum 25(OH)
      vitamin D level (4.9 +/- 7.7 vs 1.2 +/- 5.4, p = 0.006) and lower percentage of
      osteopenia (74% vs 89% p = 0.042) at 12 months. PST group subjects had better
      improvement (2.7 +/- 6.1 vs 0.2 +/- 6.7, p = 0.035, 6-month) and less
      deterioration (-3.5 +/- 9.7 vs -7.1 +/- 8.7, p = 0.036, 12-month) of dominant leg
      extension power than non-PST subjects. Some secondary outcomes were also improved
      in control groups (non-EN or non-PST). No adverse effects were reported.
      CONCLUSIONS: The three-month EN intervention resulted in short-term (3-month)
      frailty status improvement and long-term effect on bone mineral density and serum
      vitamin D (12-month) among Taiwanese community-dwelling elders. The effect of PST
      was less pronounced. TRIAL REGISTRATION: ClinicalTrials.gov: EC0970301

PMID- 23009151
TI  - Discovery of novel inhibitors of amyloid beta-peptide 1-42 aggregation.
AB  - Alzheimer's disease, characterized by deposits of amyloid beta-peptide (Abeta),
      is the most common neurodegenerative disease, but it still lacks a specific
      treatment. We have discovered five chemically unrelated inhibitors of the in
      vitro aggregation of the Abeta17-40 peptide by screening two commercial chemical
      libraries. Four of them (1-4) exhibit relatively low MCCs toward HeLa cells (17
      184 MUM). The usefulness of compounds 1-4 to inhibit the in vivo aggregation of
      Abeta1-42 has been demonstrated using two fungi models, Saccharomyces cerevisiae
      and Podospora anserina, previously transformed to express Abeta1-42. Estimated
      IC(50)s are around 1-2 MUM. Interestingly, addition of any of the four compounds
      to sonicated preformed P. anserina aggregates completely inhibited the appearance
      of SDS-resistant oligomers. This combination of HTP in vitro screening with
      validation in fungi models provides an efficient way to identify novel inhibitory
      compounds of Abeta1-42 aggregation for subsequent testing in animal models.

PMID- 23009153
TI  - Targeting the ATF4 pathway in cancer therapy.
AB  - INTRODUCTION: Activating transcription factor 4 (ATF4) is a member of the
      activating transcription factor family. ATF4 expression is increased in response
      to a diverse array of microenvironmental stresses including amino acid depletion,
      oxidative stress and endoplasmic reticulum (ER) stress that are sensed by
      upstream eukaryotic translation initiation factor 2alpha (eIF2alpha) kinases. In
      tumours, ATF4 expression is detected in hypoxic- and nutrient-deprived regions
      where it promotes metabolic homeostasis and cancer cell survival by
      transcriptionally regulating amino acid uptake and biosynthesis, autophagy, redox
      balance and angiogenesis. AREAS COVERED: The mechanism governing translational
      expression of ATF4 is discussed along with the physiological roles of ATF4 in
      growth and development. Conditions that result in ATF4 expression in tumours are
      described with a focus on the role of ATF4 in cancer progression and treatment
      resistance. Several approaches to target ATF4 are presented including strategies
      aimed at inhibiting transcriptional activity or increasing degradation,
      approaches to reduce ATF4 translation by inhibiting upstream eIF2alpha kinases
      and targeting of downstream pathways that are regulated by ATF4 including amino
      acid biosynthesis, ER-associated degradation and autophagy. EXPERT OPINION: The
      authors provide a number of suggestions that may assist in the development of
      ATF4 inhibitors.

PMID- 23009152
TI  - Design of a prostate cancer patient navigation intervention for a Veterans
      Affairs hospital.
AB  - BACKGROUND: Patient navigation programs have been launched nationwide in an
      attempt to reduce racial/ethnic and socio-demographic disparities in cancer care,
      but few have evaluated outcomes in the prostate cancer setting. The National
      Cancer Institute-funded Chicago Patient Navigation Research Program (C-PNRP) aims
      to implement and evaluate the efficacy of a patient navigation intervention for
      predominantly low-income minority patients with an abnormal prostate cancer
      screening test at a Veterans Affairs (VA) hospital in Chicago. METHODS/DESIGN:
      From 2006 through 2010, C-PNRP implemented a quasi-experimental intervention
      whereby trained social worker and lay health navigators worked with veterans with
      an abnormal prostate screen to proactively identify and resolve personal and
      systems barriers to care. Men were enrolled at a VA urology clinic and were
      selected to receive navigated versus usual care based on clinic day. Patient
      navigators performed activities to facilitate timely follow-up such as
      appointment reminders, transportation coordination, cancer education, scheduling
      assistance, and social support as needed. Primary outcome measures included time
      (days) from abnormal screening to diagnosis and time from diagnosis to treatment
      initiation. Secondary outcomes included psychosocial and demographic predictors
      of non-compliance and patient satisfaction. Dates of screening, follow-up visits,
      and treatment were obtained through chart audit, and questionnaires were
      administered at baseline, after diagnosis, and after treatment initiation. At the
      VA, 546 patients were enrolled in the study (245 in the navigated arm, 245 in the
      records-based control arm, and 56 in a subsample of surveyed control subjects).
      DISCUSSION: Given increasing concerns about balancing better health outcomes with
      lower costs, careful examination of interventions aimed at reducing healthcare
      disparities attain critical importance. While analysis of the C-PNRP data is
      underway, the design of this patient navigation intervention will inform other
      patient navigation programs addressing strategies to improve prostate cancer
      outcomes among vulnerable populations.

PMID- 23009154
TI  - Topical ganciclovir treatment in patients with cytomegalovirus endotheliitis
      receiving penetrating keratoplasty.
AB  - BACKGROUND: To report seven cases diagnosed as cytomegalovirus endotheliitis and
      treated with topical 2% ganciclovir following penetrating keratoplasty. DESIGN: A
      retrospectively comparative case series. PARTICIPANTS: A retrospective
      interventional case series, including seven eyes of seven patients with
      cytomegalovirus endotheliitis after penetrating keratoplasty. METHODS: Clinical
      and immunological characteristics were studied in seven penetrating keratoplasty
      cases with positive quantitative polymerase chain reaction results for
      cytomegalovirus DNA from aqueous taps and treated with topical 2% ganciclovir.
      MAIN OUTCOME MEASURES: Clinical features and responses to topical 2% ganciclovir.
      RESULTS: Seven immunocompetent patients experienced acute anterior inflammation
      with graft oedema and pigmented keratic precipitates after penetrating
      keratoplasty. Their immunological profiles showed immunoglobulin G
      cytomegalovirus (+) and immunoglobulin M cytomegalovirus (-) in all cases.
      Topical 2% ganciclovir was prescribed every 2 to 3 h daily as induction therapy
      and every 4 h as long-term maintenance therapy. All cases had undetectable
      cytomegalovirus DNA after follow-up aqueous taps. Topical 2% ganciclovir
      preserved endothelium of cytomegalovirus-infected grafts at early stage and also
      provided a steady anticytomegalovirus environment for further regrafting in
      failed grafts at late stage. Acute inflammation reactivated in two cases and was
      suppressible by steroid under topical ganciclovir. No delayed re
      epithelialization and any toxicity were observed. To date, no case treated in
      this way had displayed cytomegalovirus recurrence. CONCLUSIONS: Continuous
      topical 2% ganciclovir and a topical steroid adjusted by anterior inflammation
      are suggested after penetrating keratoplasty in all cases with cytomegalovirus
      endotheliitis to prevent cytomegalovirus recurrence.

PMID- 23009156
TI  - Sensitivity of common carp, Cyprinus carpio L., strains and crossbreeds reared in
      the Czech Republic to infection by cyprinid herpesvirus 3 (CyHV-3; KHV).

PMID- 23009157
TI  - Encapsulation of an adamantane-doxorubicin prodrug in pH-responsive
      polysaccharide capsules for controlled release.
AB  - Supramolecular microcapsules (SMCs) with the drug-loaded wall layers for pH
      controlled drug delivery were designed and prepared. By using layer-by-layer
      (LbL) technique, the SMCs were constructed based on the self-assembly between
      polyaldenhyde dextran-graft-adamantane (PAD-g-AD) and carboxymethyl dextran-graft
      beta-CD (CMD-g-beta-CD) on CaCO(3) particles via host-guest interaction.
      Simultaneously, adamantine-modified doxorubicin (AD-Dox) was also loaded on the
      LbL wall via host-guest interaction. The in vitro drug release study was carried
      out at different pHs. Because the AD groups were linked with PAD (PAD-g-AD) or
      Dox (AD-Dox) by pH-cleavable hydrazone bonds, AD moieties can be removed under
      the weak acidic condition, leading to destruction of SMCs and release of Dox. The
      pH-controlled drug release can enhance the uptake by tumor cells and thus achieve
      improved cancer therapy efficiency.

PMID- 23009158
TI  - Reaction of Cu(I) with dialkyl peroxides: Cu(II)-alkoxides, alkoxy radicals, and
      catalytic C-H etherification.
AB  - Kinetic analysis of the reaction of the copper(I) beta-diketiminate [Cl(2)NN]Cu
      ([Cu(I)]) with (t)BuOO(t)Bu to give [Cu(II)]-O(t)Bu (1) reveals first-order
      behavior in each component implicating the formation of free (t)BuO(*) radicals.
      Added pyridine mildly inhibits this reaction indicating competition between
      (t)BuOO(t)Bu and py for coordination at [Cu(I)] prior to peroxide activation.
      Reaction of [Cu(I)] with dicumyl peroxide leads to [Cu(II)]-OCMe(2)Ph (3) and
      acetophenone suggesting the intermediacy of the PhMe(2)CO(*) radical.
      Computational methods provide insight into the activation of (t)BuOO(t)Bu at
      [Cu(I)]. The novel peroxide adduct [Cu(I)]((t)BuOO(t)Bu) (4) and the square
      planar [Cu(III)](O(t)Bu)(2) (5) were identified, each unstable toward loss of the
      (t)BuO(*) radical. Facile generation of the (t)BuO(*) radical is harnessed in the
      catalytic C-H etherification of cyclohexane with (t)BuOO(t)Bu at rt employing
      [Cu(I)] (5 mol %) to give the ether Cy-O(t)Bu in 60% yield.

PMID- 23009155
TI  - Description and outcome of a cohort of 8 patients with WHIM syndrome from the
      French Severe Chronic Neutropenia Registry.
AB  - BACKGROUND: WHIM syndrome (WS), a rare congenital neutropenia due to mutations of
      the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)
      induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The
      long term follow up of eight patients highlights the clinical heterogeneity of
      this disease as well as the main therapeutic approaches and remaining challenges
      in the light of the recent development of new CXCR4 inhibitors. OBJECTIVE: This
      study aims to describe the natural history of WS based on a French cohort of 8
      patients. METHODS: We have reviewed the clinical, biological and immunological
      features of patients with WS enrolled into the French Severe Chronic Neutropenia
      Registry. RESULTS: We identified four pedigrees with WS comprised of eight
      patients and one foetus. Estimated incidence for WS was of 0.23 per million
      births. Median age at the last visit was 29 years. Three pedigrees encompassing
      seven patients and the fetus displayed autosomal dominant heterozygous mutations
      of the CXCR4 gene, while one patient presented a wild-type CXCR4 gene. Two
      subjects exhibited congenital conotruncal heart malformations. In addition to
      neutropenia and myelokathexis, all patients presented deep monocytopenia and
      lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well
      as severe bacterial infections that were curable with antibiotics. Four patients
      with late onset prophylaxis developed chronic obstructive pulmonary disease
      (COPD). Two patients reported atypical mycobacteria infections which in one case
      may have been responsible for one patient's death due to liver failure at the age
      of 40.6 years. HPV-related disease manifested in five subjects and progressed as
      invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5
      years. In addition, two patients developed T cell lymphoma skin cancer and basal
      cell carcinoma at the age of 38 and 65 years. CONCLUSIONS: Continuous
      prophylactic anti-infective measures, when started in early childhood, seem to
      effectively prevent further bacterial infections and the consequent development
      of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV
      targeted prophylaxis on the development of skin and genital warts.

PMID- 23009159
TI  - Epithelial-to-mesenchymal transdifferentiation of renal tubular epithelial cell
      mediated by oxidative stress and intervention effect of probucol in diabetic
      nephropathy rats.
AB  - OBJECTIVE: To elucidate the relationship of oxidative stress and specificity
      protein 1 (Sp1) in the process of epithelial-to-mesenchymal transdifferentiation
      (EMT) and also to investigate the molecular mechanism of protective effect of
      probucol on the pathogenesis of diabetic kidney disease (DKD). METHODS: Thirty
      male Sprague-Dawley (SD) rats were randomly divided into control group, diabetic
      group, and diabetic group under probucol therapy (n = 10 per group). The
      biochemical indicators including 24-h urinary total protein (24-h UTP) excretion,
      blood glucose (BG), lipids [triglycerides (TGs), total cholesterol (TC)], serum
      creatinine (Scr), creatinine clearance rate (Ccr), kidney tissue malondialdehyde
      (MDA) level, and glutathione peroxidase (GSH-Px) activity were assessed in all
      groups. The renal pathological changes were evaluated by hematoxylin and eosin
      (HE) and Masson staining. The protein expression of Sp1, alpha-smooth muscle
      actin (alpha-SMA), and E-cadherin was also measured and analyzed by
      immunohistochemistry and Western blotting. RESULTS: Compared with the control
      group, the BG, TC, Scr, 24-h UTP, and MDA level of renal tissue increased
      significantly and the Ccr reduced in the rats of diabetic group (all p < 0.01).
      The pathological scores and the expression of Sp1 and alpha-SMA in renal tissue
      were up-regulated (p < 0.01) and the expression of E-cadherin was down-regulated
      significantly in the diabetic animals (p < 0.01). In the diabetic animals treated
      with probucol, the renal injuries were alleviated (p < 0.01). CONCLUSIONS:
      Oxidative stress may play an important role in the EMT process of tubular
      epithelial cells. Probucol could ameliorate renal disease progression in this
      model of diabetic nephropathy, which might be due to an antioxidant action, down
      regulation of Sp1 protein expression, and inhibition of renal tubular EMT.

PMID- 23009160
TI  - The effect of ketamine on intraocular pressure in pediatric patients during
      procedural sedation.
AB  - OBJECTIVES: Ketamine is one of the most commonly used procedural sedation and
      analgesia (PSA) agents in pediatric emergency departments (PEDs). It is
      considered a very safe and reliable agent, with limited respiratory suppression,
      hemodynamic effects, and adverse outcomes. However, physicians are often
      reluctant to use ketamine for patients with eye injuries due to a concern that
      ketamine might increase intraocular pressure (IOP). The objective was to measure
      IOP in previously healthy children receiving ketamine for PSA for a reason other
      than eye injury. METHODS: This was a prospective noninferiority study of patients
      seen in an academic tertiary care children's hospital emergency department (ED)
      who required ketamine for PSA. The authors measured IOP in the right eye as soon
      as possible after ketamine had been administered and then at 2.5, 5, and 10
      minutes after ketamine had been administered. RESULTS: Eighty patients were
      enrolled (28 between 1 and 5 years of age, 26 between 6 and 10 years, 26 between
      11 and 15 years); 49 (61%) were male. Procedures requiring PSA included
      fracture/dislocation reduction (63%), abscess incision and drainage (16%),
      laceration repair (11%), dental abscess incision and drainage (6%), and other
      (4%). The mean total ketamine dosage was 1.6 mg/kg (95% confidence interval [CI]
      = 1.4 to 1.7). The mean initial IOP was 17.5 mm Hg (95% CI = 16.4 to 18.6 mm Hg)
      and at 2.5 minutes was 18.9 mm Hg (95% CI = 17.9 to 19.9 mm Hg). The mean
      difference was 1.4 mm Hg (95% CI = 0.4 to 2.4 mm Hg). Using a noninferiority
      margin of 2.6 mm Hg (15%), noninferiority (no significant elevation in IOP) was
      demonstrated with 95% confidence between the first and second readings.
      CONCLUSIONS:  Ketamine does not significantly increase IOP in pediatric patients
      without eye injuries receiving typical PSA dosages in the PED. Further study
      should assess its safety in patients with ocular injury.

PMID- 23009161
TI  - Barriers and facilitators to mental health help-seeking for young elite athletes:
      a qualitative study.
AB  - BACKGROUND: Adolescents and young adults experience a high level of mental
      disorders, yet tend not to seek help. Research indicates that there are many
      barriers and facilitators to help-seeking for young people in the general
      community. However there are limited data available for young elite athletes.
      This study aims to determine what young elite athletes perceive as the barriers
      and facilitators to help-seeking for common mental health problems. METHODS:
      Fifteen elite athletes aged 16-23 years each participated in one of three focus
      group discussions. In addition to written data, verbal responses were audio
      taped, transcribed and thematically analysed. RESULTS: Participants' written and
      verbal data suggested that stigma was the most important perceived barrier to
      seeking help for young elite athletes. Other notable barriers were a lack of
      mental health literacy, and negative past experiences of help-seeking.
      Facilitators to help-seeking were encouragement from others, having an
      established relationship with a provider, pleasant previous interactions with
      providers, the positive attitudes of others, especially their coach, and access
      to the internet. CONCLUSIONS: Intervention strategies for improving help-seeking
      in young elite athletes should focus on reducing stigma, increasing mental health
      literacy, and improving relations with potential providers.

PMID- 23009162
TI  - Electrochemical oxidation of pyrogallol: formation and characterization of long
      lived oxygen radicals and application to assess the radical scavenging abilities
      of antioxidants.
AB  - Electrochemical oxidation of pyrogallol in a pH 5.0 phosphate buffer was carried
      out on a reduced graphene oxide/glassy carbon (RGO/GC) electrode. Reduced
      graphene oxide plays an important role in catalyzing the electrochemical
      oxidation of pyrogallol. A deep yellow film deposited on the electrode exhibits
      electroactivity in a wide pH range. On the basis of the experimental results from
      measurements of (1)H NMR, (13)C NMR, and IR spectra, there are  hydroxyl,
      carbonyl, and aldehyde groups in the product. No visible absorption peak occurs
      in the UV-vis spectrum of the product, and its molecular weight is lower than
      that of the dipolymer but higher than that of the monomer. Therefore, the film is
      neither a polymer nor a dipolymer and is only a product of pyrogallol oxidation
      with oxygen radicals. No tendency toward the decay of the ESR signal intensity of
      the electrogenerated film deposited on the RGO/graphite electrode was observed
      after 210 days. Electrogenerated film was used as a radical source to test the
      radical scavenging abilities of ascorbic acid, catechin, and catechol in  aqueous
      solutions based on the ESR signal intensity. The result indicates that ascorbic
      acid and catechin can scavenge the free radicals, but catechol can hardly
      scavenge the free radicals.

PMID- 23009163
TI  - Reflective action assessment with a prospective clinical problem solving tool in
      the context of rehabilitation medicine: an illustrative case study.
AB  - PURPOSE: This study describes a case formulation approach applying a prospective
      ICF derived clinical tool to assess rehabilitation needs for a community dwelling
      stroke survivor with care from an outpatient rehabilitation medicine clinic.
      METHOD: Case history data on the person were assessed for rehabilitation
      management planning using a prospective tool to interlink current with projected
      future functional status in everyday settings. Implicit assessment with
      reflective action informed decision points at each stage of the rehabilitation
      process. RESULTS: As a result of reflective action using the prospective tool,
      rehabilitation management led to significant changes in client participation
      after limitations to mobility and self care were mapped to the living conditions
      of the stroke survivor. The context sensitive rehabilitative plan resulted in
      higher subjective health-related quality of life in the stroke survivor and
      significant other and enhanced their capacity for participation. CONCLUSIONS:
      Reflective action informed assessment applying ICF concepts to clinical problem
      solving resulted in positive gains in health-related quality of life in a stroke
      survivor.

PMID- 23009164
TI  - Layered metal sulfides capture uranium from seawater.
AB  - Uranium is the main source for nuclear energy but also one of the most toxic
      heavy metals. The current methods for uranium removal from water present
      limitations, such as narrow pH operating range, limited tolerance to high salt
      concentrations, or/and high cost. We show here that a layered sulfide ion
      exchanger K(2)MnSn(2)S(6) (KMS-1) overcomes these limitations and is
      exceptionally capable in selectively and rapidly sequestering high (ppm) as well
      as trace (ppb) quantities of UO(2)(2+) under a variety of conditions, including
      seawater. KMS-1 can efficiently absorb the naturally occurring U traces in
      seawater samples. The results presented here reveal the exceptional potential of
      sulfide-based ion-exchangers for remediating of uranium-containing wastes and
      groundwater and for extracting uranium from the sea.

PMID- 23009165
TI  - Pulsatile paracorporeal pump membrane rupture: clinical advantage of a multilayer
      membrane.

PMID- 23009166
TI  - Reactive adsorption of PS-PMMA block copolymers on concave alumina surfaces.
AB  - The influence of pore size, relative block size, and solvent quality on the
      extent of diblock copolymer adsorption on alumina surfaces was determined. To
      this end, the block copolymer that was chosen was poly(styrene)-b-poly(methyl
      methacrylate) (PS-b-PMMA), in which the PMMA block strongly chemisorbs to the
      surface and the PS block weakly physisorbs. Several architectures (i.e.,
      different ratios of M(n(PMMA)) and M(n)((PS))) of the PS-b-PMMA copolymers were
      adsorbed from various solvents onto porous alumina membranes with various pore
      sizes. It was determined that the diblock copolymer coverage decreased
      significantly as the pore size decreased, similar to the behavior of the PMMA
      homopolymer under the same conditions. However, the coverage decreased as the
      molecular weight of the anchoring block (PMMA) increased for all pore sizes,
      which is in contrast to the behavior of the PMMA homopolymer under the same
      conditions. The dependence of the coverage on the relative block size and solvent
      quality is analyzed on the basis of the anchor-buoy model and the deviation from
      it in a nonideal system. The results presented in this work are relevant to the
      study of block copolymer conformation in solutions and on surfaces, adsorption
      chromatography, and solvent sensors and controls.

PMID- 23009167
TI  - Cross-reactive antibody response to the pandemic A (H1N1) 2009 influenza virus
      induced by vaccination with a seasonal trivalent influenza vaccine: a
      longitudinal study of three influenza seasons in Japan.
AB  - The cross-reactivity of antibody to the swine-origin pandemic influenza A (H1N1)
      2009 virus induced by vaccination with a seasonal trivalent influenza vaccine was
      studied. Paired sera from a cohort of adult volunteers vaccinated with a
      trivalent seasonal influenza vaccine every year from 2006 to 2008 were collected
      each year and tested by hemagglutination inhibition (HI) for antibody against the
      pandemic influenza A (H1N1) 2009 virus. There was little increase in the
      geometric mean titer overall; a slight increase was detected in the sera obtained
      in the 2007-2008 season but not in the other two seasons. The proportion of
      individuals with HI antibody titers >= 1:40 did not change significantly from
      year to year. These results indicate that cross-reactivity of the antibodies
      induced by a trivalent seasonal vaccine to the pandemic influenza A (H1N1) 2009
      virus is marginal.

PMID- 23009168
TI  - Magnetic Mn5Ge3 nanocrystals embedded in crystalline Ge: a magnet/semiconductor
      hybrid synthesized by ion implantation.
AB  - The integration of ferromagnetic Mn5Ge3 with the Ge matrix is promising for spin
      injection in a silicon-compatible geometry. In this paper, we report the
      preparation of magnetic Mn5Ge3 nanocrystals embedded inside the Ge matrix by Mn
      ion implantation at elevated temperature. By X-ray diffraction and transmission
      electron microscopy, we observe crystalline Mn5Ge3 with variable size depending
      on the Mn ion fluence. The electronic structure of Mn in Mn5Ge3 nanocrystals is a
      3d6 configuration, which is the same as that in bulk Mn5Ge3. A large positive
      magnetoresistance has been observed at low temperatures. It can be explained by
      the conductivity inhomogeneity in the magnetic/semiconductor hybrid system.

PMID- 23009171
TI  - Occurrence and characterization of monophasic Salmonella enterica serovar
      typhimurium (1,4,[5],12:i:-) of non-human origin in Poland.
AB  - The epidemiological role of monophasic Salmonella enterica subsp. enterica
      serovar Typhimurium tends to increase, indicating pandemic spread. The aim of the
      present study was to confirm the occurrence of this serological variant in Poland
      and to report the first cases in Belarus and Ukraine. Genetic similarity of
      monophasic isolates with Salmonella Typhimurium already present in these
      countries was assessed. Serotyping, duplex-polymerase chain reaction (PCR) assay,
      antibiotic resistance and pulsed-field gel electrophoresis (PFGE) profiling have
      been used to meet the study objectives. Monophasic Salmonella Typhimurium was
      found at low frequency in various sources along the food chain, including feed,
      animals, meat, and sewage sludge. The first isolates date back to 2008. The
      clones observed in other European countries were found, along with a number of
      new, unrelated genetic lineages appearing locally in three countries. Monophasic
      Salmonella Typhimurium is claimed to replace and discontinue the domination of
      pentaresistant Salmonella Typhimurium. Pigs and pork are assumed to be the main
      vectors of monophasic Salmonella Typhimurium, but their relevance for public
      health is limited.

PMID- 23009170
TI  - Enhanced identification and characterization of non-O157 Shiga toxin-producing
      Escherichia coli: a six-year study.
AB  - Non-O157 Shiga toxin-producing Escherichia coli (STEC) are emerging pathogens
      with the potential to cause serious illness and impact public health due to
      diagnostic challenges. Between 2005 and 2010, the Wadsworth Center (WC), the
      public health laboratory of the New York State (NYS) Department of Health,
      requested that Shiga toxin enzyme immunoassay (EIA)-positive stool enrichment
      broths and/or stool specimens be submitted by clinical and commercial reference
      laboratories testing NYS patient specimens. A total of 798 EIA-positive specimens
      were received for confirmation and serotyping, and additionally a subset of STEC
      was assessed for the presence of six virulence genes (stx1, stx2, eaeA, hlyA,
      nleA, and nleB) by real-time polymerase chain reaction. We confirmed 591
      specimens as STEC, 164 (28%) as O157 STEC, and 427 (72%) as non-O157 STEC. Of the
      non-O157 STEC serogroups identified, over 70% were O103, O26, O111, O45, O121, or
      O145. During this time period, WC identified and characterized a total of 1282
      STEC received as E. coli isolates, stool specimens, or EIA broths. Overall, the
      STEC testing identified 59% as O157 STEC and 41% as non-O157 STEC; however, out
      of 600 isolates submitted to the WC as E. coli cultures, 543 (90%) were
      identified as O157 STEC. This report summarizes a 6-year study utilizing enhanced
      STEC testing that resulted in increased identification and characterization of
      non-O157 STEC in NYS. Continued utilization of enhanced STEC testing may lead to
      effective and timely outbreak response and improve monitoring of trends in STEC
      disease epidemiology.

PMID- 23009169
TI  - Development of oseltamivir phosphonate congeners as anti-influenza agents.
AB  - Oseltamivir phosphonic acid (tamiphosphor, 3a), its monoethyl ester (3c),
      guanidino-tamiphosphor (4a), and its monoethyl ester (4c) are potent inhibitors
      of influenza neuraminidases. They inhibit the replication of influenza viruses,
      including the oseltamivir-resistant H275Y strain, at low nanomolar to picomolar
      levels, and significantly protect mice from infection with lethal doses of
      influenza viruses when orally administered with 1 mg/kg or higher doses. These
      compounds are stable in simulated gastric fluid, liver microsomes, and human
      blood and are largely free from binding to plasma proteins. Pharmacokinetic
      properties of these inhibitors are thoroughly studied in dogs, rats, and mice.
      The absolute oral bioavailability of these compounds was lower than 12%. No
      conversion of monoester 4c to phosphonic acid 4a was observed in rats after
      intravenous administration, but partial conversion of 4c was observed with oral
      administration. Advanced formulation may be investigated to develop these new
      anti-influenza agents for better therapeutic use.

PMID- 23009172
TI  - Functional diversity of CYCLOIDEA-like TCP genes in the control of zygomorphic
      flower development in Lotus japonicus.
AB  - CYCLOIDEA (CYC)-like TCP genes play key roles in dorsoventral differentiation of
      zygomorphic flowers in Papilionoideae legumes. In this study, we analyzed the kew
      mutants whose flowers lost lateral identity, and investigated the diverse
      functions of three LjCYC genes during zygomorphic flower development in the model
      legume Lotus japonicus. We showed that kew1 and kew3 are allelic mutants of
      LjCYC3, a CYC-like TCP gene. Through transgenic experiments, it was shown that
      LjCYC1 possesses dorsal activity similar to LjCYC2, and that LjCYC3 alone is
      sufficient to confer lateral activity, and an epistatic effect between dorsal and
      lateral activities was identified. Sequence analysis revealed a striking
      alteration at the 3' end of the LjCYC3 open reading frame (ORF) in comparison
      with those of LjCYC1 and LjCYC2 ORFs. Furthermore, it was found that LjCYC
      proteins could interact with each other and possess different activities by means
      of a transcriptional activity assay. Our data demonstrate that the sequence
      variation and the subsequent alteration of protein property play important roles
      in the functional diversity of different LjCYC genes in controlling zygomorphic
      flower development in Lotus japonicus.

PMID- 23009173
TI  - Identifying resident care areas for a quality improvement intervention in long
      term care: a collaborative approach.
AB  - BACKGROUND: In Canada, healthcare aides (also referred to as nurse aides,
      personal support workers, nursing assistants) are unregulated personnel who
      provide 70-80% of direct care to residents living in nursing homes. Although they
      are an integral part of the care team their contributions to the resident care
      planning process are not always acknowledged in the organization. The purpose of
      the Safer Care for Older Persons [in residential] Environments (SCOPE) project
      was to evaluate the feasibility of engaging front line staff (primarily
      healthcare aides) to use quality improvement methods to integrate best practices
      into resident care. This paper describes the process used by teams participating
      in the SCOPE project to select clinical improvement areas. METHODS: The study
      employed a collaborative approach to identify clinical areas and through
      consensus, teams selected one of three areas. To select the clinical areas we
      recruited two nursing homes not involved in the SCOPE project and sampled
      healthcare providers and decision-makers within them. A vote counting method was
      used to determine the top five ranked clinical areas for improvement. RESULTS:
      Responses received from stakeholder groups included gerontology experts, decision
      makers, registered nurses, managers, and healthcare aides. The top ranked areas
      from highest to lowest were pain/discomfort management, behaviour management,
      depression, skin integrity, and assistance with eating. CONCLUSIONS: Involving
      staff in selecting areas that they perceive as needing improvement may facilitate
      staff engagement in the quality improvement process.

PMID- 23009174
TI  - Sublingual vs oral immunotherapy for food allergy: identifying the right
      approach.
AB  - The incidence of food allergy in developed countries has increased in recent
      years, escalating the need to find a suitable form of treatment as an alternative
      to current management, which includes strict avoidance and ready availability of
      injectable epinephrine (adrenaline). Allergen immunotherapy is currently being
      studied for use in the treatment of IgE-mediated food allergy to the most common
      foods, including peanut, tree nut, milk and egg. Two modalities, oral
      immunotherapy (OIT) and sublingual immunotherapy (SLIT), have shown great
      promise. Both OIT and SLIT have been able to desensitize subjects to varying
      degrees, but the two treatment methods differ in doses that can be achieved,
      duration of treatment, safety profile and ease of use outside the research
      setting, among other aspects. More research is needed to conclude which mode of
      treatment is more effective in inducing long-term tolerance with the least amount
      of serious adverse reactions. However, OIT and SLIT show great promise, and a
      widespread treatment for food allergy may be within reach.

PMID- 23009175
TI  - Concomitance of Gitelman syndrome and familial Mediterranean fever: a rare case
      presentation.
AB  - We report a case that has Gitelman syndrome (GS) and familial Mediterranean fever
      (FMF) presenting with recurrent arthritis of right knee and heel pain.
      Investigations showed hypokalemia and hypomagnesemia with urinary magnesium
      wasting. Genetic analysis revealed the presence of heterozygous E148Q mutation in
      the MEFV gene. Management with potassium, magnesium supplements, spironolactone
      for GS, and colchicine for FMF resulted in a significant improvement in symptoms.
      To the best of our knowledge, this is the first report of association between GS
      and FMF. Further studies are needed to identify if there is an association
      between these two diseases and the genes responsible for these diseases.

PMID- 23009176
TI  - Treatment patterns of childhood diarrhoea in rural Uganda: a cross-sectional
      survey.
AB  - BACKGROUND: Diarrhoea is the second leading cause of death in children under five
      accounting for 1.8 million deaths yearly. Despite global efforts to reduce
      diarrhoea mortality through promotion of proper case management, there is still
      room for ample improvement. In order to seek options for such improvements this
      study explored the knowledge and practices of diarrhoea case management among
      health care providers at health centres and drug shops in Uganda. METHODS:
      Records were reviewed for case management and structured interviews concerning
      knowledge and practices were conducted with the staff at all health centres and
      at all identified drug shops in the rural district of Namutumba, Uganda. RESULTS:
      There was a significant gap between knowledge and documented practices among
      staff. Antibiotics, antimalarials and antipyretics were prescribed or recommended
      as frequently as Oral Rehydration Solution (ORS). In almost a third of the health
      facilities, ORS was out of stock. 81% of staff in health centres and 87% of staff
      in drug shops stated that they prescribed antibiotics for common diarrhoea. Zinc
      was not prescribed or recommended in any case. CONCLUSIONS: The findings indicate
      that many children presenting with diarrhoea are inadequately treated. As a
      result they may not get the rehydration they need and are at risk of potential
      side effects from unjustified usage of antibiotics. Practices must be improved at
      health centres and drug shops in order to reduce childhood mortality due to
      diarrhoeal diseases.

PMID- 23009177
TI  - Toxic epidermal necrolysis, DRESS, AGEP: do overlap cases exist?
AB  - BACKGROUND: Severe cutaneous adverse reactions to drugs (SCARs) include acute
      generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and
      systemic symptoms (DRESS) and epidermal necrolysis (Stevens-Johnson syndrome
      toxic epidermal necrolysis [SJS-TEN]). Because of the varied initial presentation
      of such adverse drug reactions, diagnosis may be difficult and suggests overlap
      among SCARs. Overlapping SCARs are defined as cases fulfilling the criteria for
      definite or probable diagnosis of at least 2 ADRs according to scoring systems
      for AGEP, DRESS and SJS-TEN. We aimed to evaluate the prevalence of overlap among
      SCARs among cases in the referral hospital in France. METHODS: We retrospectively
      analyzed data for 216 patients hospitalized in the referral centre over 7 years
      with a discharge diagnosis of AGEP (n = 45), DRESS (n = 47), SJS-TEN (n = 80) or
      "drug rash" (n = 44). Each case with detailed clinical data and a skin biopsy
      specimen was scored for AGEP, DRESS and SJS-TEN by use of diagnostic scores
      elaborated by the RegiSCAR group. RESULTS: In total, 45 of 216 cases (21%) had at
      least 2 possible diagnoses: 35 had a single predominant diagnosis (definite or
      probable), 7 had several possible diagnoses and 3 (2.1% of 145 confirmed SCARs)
      were overlap SCARs. CONCLUSIONS: Despite ambiguities among SCARs, confirmed
      overlap cases are rare. This study did not avoid pitfalls linked to its
      retrospective nature and selection bias. In the acute stage of disease, early
      identification of severe ADRs can be difficult because of clinical or biologic
      overlapping features and missing data on histology, biology and evolution.
      Retrospectively analyzing cases by use of diagnostic algorithms can lead to
      reliable discrimination among AGEP, DRESS and SJS-TEN.

PMID- 23009178
TI  - DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the
      EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer.
AB  - BACKGROUND: It is well known that genetic alternation of epidermal growth factor
      receptor (EGFR) plays critical roles in tumorgenesis of lung cancer and can
      predict outcome of non-small-cell lung cancer treatment, especially the EGFR
      tyrosine-kinase inhibitors (EGFR-TKIs) therapy. However, it is unclear whether
      epigenetic changes such as DNA methylation involve in the response to the EGFR
      TKI therapy. METHODS: Tumor samples from 155 patients with stages IIIB to IV
      NSCLC who received EGFR-TKI therapy were analyzed for DNA methylation status of
      Wnt antagonist genes, including SFRP1, SFRP2, SFRP5, DKK3, WIF1, and APC, using
      methylation specific PCR (MSP) method. EGFR mutations detections were performed
      in the same tissues samples using Denaturing High Performance Liquid
      Chromatography (DHPLC). RESULTS: We found that Wnt antagonists tend to methylate
      simultaneously. Methylation of sFRP1 and sFRP5 are reversely correlated with EGFR
      mutation (P = 0.005, P = 0.011). However, no correlations of methylations of
      other Wnt antagonist genes with EGFR mutation were found. The patients with
      methylated SFRP5 have a significant shorter progression free survival than those
      with unmethylated SFRP5 in response to EGFR-TKI treatment (P = 0.002), which is
      independent of EGFR genotype. CONCLUSIONS: Patients with unmethylated SFRP5 are
      more likely to benefit from EGFR-TKI therapy.

PMID- 23009179
TI  - Implant placement under existing removable dental prostheses and its effect on
      oral health-related quality of life.
AB  - OBJECTIVE: One aim of this prospective clinical study was to measure the effects
      of strategicimplant placement under removable partial dental prostheses (RPDPs)
      and among removable complete dental prostheses (RCDPs) on oral health-related
      quality of life (OHRQoL). MATERIALS AND METHODS: Twenty-three patients
      participated in this study restored with RCDPs (n = 12) or RPDPs retained by
      telescopic crowns with 1-2 abutment teeth (n = 11). The total number of abutments
      was increased to 5-6 (maxilla) or to 4 (mandible) by placing implants in
      strategically advantageous regions. Ball attachments were attached to the
      implants and integrated in the existing denture. The Oral Health Impact Profile
      (49 questions) was completed by patients before implant placement, at baseline
      (integration of ball attachments), and during 12- and 24-month follow-up visits.
      RESULTS: There were marked reductions of impacts in both groups when comparing
      pre-treatment scores and scores at baseline (P < 0.0001), 12-month (P < 0.0001),
      and 24-month follow-up visits (P < 0.0001), respectively. For none of the visits,
      a significant difference between the two groups was detected (P > 0.05).
      CONCLUSION: It can be concluded that a strategic placement of implants under the
      existing dental prostheses improves OHRQoL in both treatment groups.

PMID- 23009180
TI  - Esophageal squamous cell carcinoma arising after endoscopic ablation therapy of
      Barrett's esophagus with high-grade dysplasia. Report of a case.
AB  - Patients with Barrett's esophagus are at risk for dysplasia and esophageal
      adenocarcinoma. Although surgery was the mainstay treatment for Barrett's
      dysplasia and cancer, patients with high-grade dysplasia and early cancers now
      have several nonsurgical treatment options. Most of the endoscopic therapies are
      relatively safe but do carry a risk for complications. Treatment failure with
      progression of the disease is the most severe complication, especially among
      patients with low surgical risk. Cryoablation has been used with promising
      results in both high-grade dysplasia and early esophageal cancer. A patient with
      a well-documented history of Barrett's esophagus with high-grade dysplasia that
      underwent multiple sessions of photodynamic therapy and salvage cryoablation for
      residual high-grade dysplasia was presented. The patient was diagnosed with
      squamous cell carcinoma of the distal esophagus approximately 1 year after
      cryoablation. This is the first complete report of squamous cell carcinoma
      occurring after endoscopic ablation for Barrett's neoplasia. Careful follow up is
      necessary in any endoscopic ablation program due to the risk of recurrent
      neoplasia.

PMID- 23009181
TI  - A benchmark comparison of sigma/sigma and pi/pi dispersion: the dimers of
      naphthalene and decalin, and coronene and perhydrocoronene.
AB  - The stacking interaction between pi systems is a well-recognized structural
      motif, but stacking between sigma systems was long considered of secondary
      importance. A recent paper points out that sigma stacking can reach the energy of
      chemical bonds and concludes that "sigma/sigma and pi/pi interactions are equally
      important" (Fokin, A. F.; Gerbig, D.; Schreiner, P. R. J. Am. Chem. Soc. 2011,
      133, 20036). Our analysis shows that strong dispersion interaction requires rigid
      subsystems and good fits of their repulsive potential walls, conditions which are
      satisfied for both graphenes and larger graphanes (perhydrographenes). Comparison
      of the dimerization energies of decalin and perhydrocoronene with those of the
      naphthalene and coronene dimers at the coupled cluster (CC) CCSD(T) level
      confirms the substantial sigma-stacking energies in graphanes but shows lower
      binding energies than do the B97D calculations of Fokin et al. Graphane
      dimerization energies are substantially lower at the CC level than the
      corresponding pi-stacking energies: the value for perhydrocoronene is only 67% of
      the value for coronene, and the difference increases with system size. Our best
      estimate for the dimerization energy of naphthalene is 6.1 kcal/mol. Spin
      component scaled MP2 is unbalanced: it gives only 70% of the CCSD(T) binding
      energy in sigma dimers. The B3LYP-D3 method compares very well with CC for both
      sigma and pi dimers at the van der Waals minimum but underestimates the binding
      at larger distances. We used the largest possible atomic basis for these systems
      with 64-bit arithmetic, half-augmented-pVDZ, and the results were corrected for
      basis set incompleteness at the MP2 level.

PMID- 23009182
TI  - Polymer-composite materials for radiation protection.
AB  - Unwanted exposures to high-energy or ionizing radiation can be hazardous to
      health. Prolonged or accumulated radiation dosage from either particle-emissions
      such as alpha/beta, proton, electron, neutron emissions, or high-energy
      electromagnetic waves such as X-rays/gamma rays, may result in carcinogenesis,
      cell mutations, organ failure, etc. To avoid occupational hazards from these
      kinds of exposures, researchers have traditionally used heavy metals or their
      composites to attenuate the radiation. However, protective gear made of heavy
      metals are not only cumbersome but also are capable of producing more penetrative
      secondary radiations which requires additional shielding, increasing the cost and
      the weight factor. Consequently, significant research efforts have been focused
      toward designing efficient, lightweight, cost-effective, and flexible shielding
      materials for protection against radiation encountered in various industries
      (aerospace, hospitals, and nuclear reactors). In this regard, polymer composites
      have become attractive candidates for developing materials that can be designed
      to effectively attenuate photon or particle radiation. In this paper, we review
      the state-of-the-art of polymer composites reinforced with micro/nanomaterials,
      for their use as radiation shields.

PMID- 23009183
TI  - Target animal safety study of meloxicam administered via transmucosal oral spray
      (Promist((r)) technology) for 6 months in dogs.
AB  - This study evaluated the safety of meloxicam administered via transmucosal oral
      spray (TMOS) at 1, 2, 3 and 5 times the maximum proposed dose for 6 months in
      dogs. After baseline assessments, 40 Beagles (20 M, 20 F) were randomized to
      gender-balanced groups administered either water or meloxicam TMOS at 1, 2, 3 and
      5 times the maximum proposed dose once daily for 26 weeks. Dogs were subjected to
      daily food consumption measurements and clinical and dose site observations.
      Periodic evaluations were made of body weight, physical examination, clinical
      pathology, urinalysis, buccal mucosal bleeding time (BMBT) and gastroduodenal
      endoscopy. At study completion, all dogs were subjected to gross necropsy.
      Histopathology was performed on tissues from dogs in groups 0X and 5X and from
      selected tissues in other dose groups. Clinical signs of previously reported
      NSAID-associated gastrointestinal upset were noted with higher frequency in
      meloxicam-dosed animals than in controls. Despite the presence of statistically
      significant effects on some clinicopathological variables, no toxicologically
      relevant dose-associated effects were determined on these or on food consumption,
      dose site observations, body weight, physical examination, urinalysis, BMBT,
      endoscopic examination or gross and histopathological examination of necropsy
      tissues. 

PMID- 23009184
TI  - Single-incision versus conventional laparoscopic cholecystectomy: a meta
      analysis.
AB  - BACKGROUND: Conventional laparoscopic cholecystectomy (CLC) is now accepted as
      the gold standard surgical treatment for gallbladder stone disease. Single
      incision laparoscopic technology has recently been introduced into laparoscopic
      clinical practice in order to reduce the invasiveness of this procedure. A meta
      analysis of randomized clinical trials (RCTs) was performed to compare single
      incision laparoscopic cholecystectomy (SICL) and CLC. METHODS: Medline, Embase,
      ISI Web of Knowledge CPCI-S and the Cochrane Library were searched and the
      methodological quality of the included trials was evaluated. Outcomes evaluated
      were adverse events, conversion rate, post-operative hospital stay, blood loss,
      post-operative pain, total wound length, operative time and wound satisfaction
      score. Results were pooled in meta-analyses as odds ratio and weighted mean
      differences (WMD). RESULTS: Five RCTs on 264 patients qualified for the meta
      analysis, 139 being allocated to SILC and 125 to CLC. There was no significant
      difference between SICL and CLC for adverse events, conversion rate, post
      operative hospital stay, blood loss, post-operative pain and total wound length;
      however, operative time was significantly longer in SICL than in CLC (WMD 7.72
      (95% confidence interval (CI): 1.38-14.07) min; P = 0.02, chi(2)  P = 0.02, I(2) 
      = 69%). Furthermore, wound satisfaction score was significantly higher in SICL
      than in CLC (WMD 1.40 (95% CI: 1.19-1.61) min; P < 0.00001, chi(2)  P = 0.19,
      I(2)  = 42%). CONCLUSION: SILC may be superior to CLC in terms of cosmetic
      outcome, but not in operative time. Currently, SILC is a safe procedure for
      proper patients in experienced surgeons.

PMID- 23009185
TI  - Predictors of overweight and obesity in adult women in Nairobi Province, Kenya.
AB  - BACKGROUND: Since obesity in urban women is prevalent in Kenya the study aimed to
      determine predictors of overweight and obesity in urban Kenyan women. METHODS: A
      cross-sectional study was undertaken in Nairobi Province. The province was
      purposively selected because it has the highest prevalence of overweight and
      obesity in Kenya.A total of 365 women aged 25-54 years old were randomly selected
      to participate in the study. RESULTS: Higher age, higher socio-economic (SE)
      group, increased parity, greater number of rooms in the house, and increased
      expenditure showed greater mean body mass index (BMI),% body fat and waist
      circumference (WC) at highly significant levels (p <0.001). Most of the variance
      in BMI was explained by age, total physical activity, percentage of fat consumed,
      parity and SE group in that order, together accounting for 18% of the variance in
      BMI. The results suggest that age was the most significant predictor of all the
      dependent variables appearing first in all the models, while parity was a
      significant predictor of BMI and WC. The upper two SE groups had significantly
      higher mean protein (p <0.05), cholesterol (p <0.05) and alcohol (p <0.001)
      intakes than the lower SE groups; while the lower SE groups had significantly
      higher mean fibre (p <0.001) and carbohydrate (p <0.05) intakes. A fat intake
      greater than 100% of the DRI dietary reference intake (DRI) had a significantly
      greater mean BMI (p <0.05) than a fat intake less than the DRI. CONCLUSIONS: The
      predictors of overweight and obesity showed that urbanization and the nutrition
      transition were well established in the sample of women studied in the high SE
      groups. They exhibited a sedentary lifestyle and consumed a diet high in energy,
      protein, fat, cholesterol, and alcohol and lower in fibre and carbohydrate
      compared with those in the low SE groups.

PMID- 23009186
TI  - Adjunctive atropine versus metoclopramide: can we reduce ketamine-associated
      vomiting in young children? a prospective, randomized, open, controlled study.
AB  - OBJECTIVES: Pediatric procedural sedation and analgesia (PPSA) with ketamine
      administration occurs commonly in the emergency department (ED). Although
      ketamine-associated vomiting (KAV) is a less serious complication of ketamine
      administration, it seems to be cumbersome and not uncommon. The authors evaluated
      the incidence of KAV and the prophylactic effect of adjunctive atropine and
      metoclopramide in children receiving ketamine sedation in the ED setting.
      METHODS: This prospective, randomized, open, controlled study was conducted in
      children receiving ketamine sedation in the ED of a university-affiliated,
      tertiary hospital with 85,000 ED visits, including 32,000 pediatric patients from
      October 2010 to September 2011. The primary outcome was a measure of the
      incidence of KAV in the ED and after discharge according to the adjunctive drug
      administered. Secondary outcome measures included the time to resumption of a
      normal diet after ketamine sedation. RESULTS: Of the 1,883 children administered
      ketamine for primary wound repair during the study period, a convenience sample
      of 338 patients aged 4 months to 5 years was enrolled. The incidences of KAV were
      28.4% in the ketamine alone group, 27.9% in the ketamine with adjunctive atropine
      group, and 31.2% in the ketamine with adjunctive metoclopramide group (p = 0.86).
      The vomiting rate after discharge was 9.2% in the ketamine alone group. The
      nothing-by-mouth (NPO) status before sedation did not influence the incidence of
      KAV in any of the groups. Mean times to resumption of normal diet after ketamine
      administration were 7 hours 59 minutes in the ketamine alone group, 7 hours 35
      minutes in the ketamine with atropine group, and 8 hours 1 minute in the ketamine
      with metoclopramide group (p = 0.64). CONCLUSIONS:  In this study, a high rate
      (28.4%) of KAV was observed, consistent with prior reports using the
      intramuscular (IM) route. However, the authors were unable to reduce KAV using
      adjunctive atropine or metoclopramide. Parents or caregivers should be given more
      detailed discharge instructions about vomiting and diet considering the
      relatively long time to resuming a normal diet after ketamine sedation and the
      fact that KAV often occurred after ED discharge.

PMID- 23009187
TI  - Chemical resistance of disposable nitrile gloves exposed to simulated movement.
AB  - Large discrepancies between laboratory permeation testing and field exposures
      have been reported, with indications that hand movement could account for a
      portion of these differences. This study evaluated the influence of simulated
      movement on chemical permeation of 30 different disposable nitrile glove
      products. Products were investigated out-of-box and with exposure to simulated
      whole-glove movement. Permeation testing was conducted using ethanol as a
      surrogate test chemical. A previously designed pneumatic system was used to
      simulate hand movement. No movement and movement tests were matched-paired to
      control for environmental conditions, as were statistical analyses. Permeation
      data were collected for a 30-min exposure period or until a breakthrough time
      (BT) and steady-state permeation rate (SSPR) could be determined. A third
      parameter, area under the curve at 30 min (AUC-30), was used to estimate
      potential worker exposure. With movement, a significant decrease in BT (p <=
      0.05), ranging from 6-33%, was observed for 28 products. The average decrease in
      BT was 18% (p <= 0.001). With movement, a significant increase in SSPR (p <=
      0.05), ranging from 1-78%, was observed with 25 products. The average increase in
      SSPR was 18% (p <= 0.001). Significant increases in AUC-30 (p <= 0.05), ranging
      from 23-277%, were also observed for all products where it could be calculated.
      On average, there was a 58% increase (p <= 0.001). The overall effect of movement
      on permeation through disposable nitrile gloves was significant. Simulated
      movement significantly shortened the BT, increased the SSPR, and increased the
      cumulative 30-min exposure up to three times. Product variability also accounted
      for large differences, up to 40 times, in permeation and cumulative exposure.
      Glove selection must take these factors into account. It cannot be assumed that
      all products will perform in a similar manner.

PMID- 23009188
TI  - Rate determination of azide click reactions onto alkyne polymer brush scaffolds:
      a comparison of conventional and catalyst-free cycloadditions for tunable surface
      modification.
AB  - The postpolymerization functionalization of poly(N-hydroxysuccinimide 4
      vinylbenzoate) brushes with reactive alkynes that differ in relative rates of
      activity of alkyne-azide cycloaddition reactions is described. The alkyne-derived
      polymer brushes undergo "click"-type cycloadditions with azido-containing
      compounds by two mechanisms: a strain-promoted alkyne-azide cycloaddition (SPAAC)
      with dibenzocyclooctyne (DIBO) and azadibenzocyclooctyne (ADIBO) or a copper
      catalyzed alkyne-azide cycloaddition (CuAAC) to a propargyl group (PPG). Using a
      pseudo-first-order limited rate equation, rate constants for DIBO, ADIBO, and PPG
      derivatized polymer brushes functionalized with an azide-functionalized dye were
      calculated as 7.7 * 10(-4), 4.4 * 10(-3), and 2.0 * 10(-2) s(-1), respectively.
      The SPAAC click reactions of the surface bound layers were determined to be
      slower than the equivalent reactions in solution, but the relative ratio of the
      reaction rates for the DIBO and ADIBO SPAAC reactions was consistent between
      solution and the polymer layer. The rate of functionalization was not influenced
      by the diffusion of azide into the polymer scaffold as long as the concentration
      of azide in solution was sufficiently high. The PPG functionalization by CuAAC
      had an extremely fast rate, which was comparable to other surface click reaction
      rates. Preliminary studies of dilute solution azide functionalization indicate
      that the diffusion-limited regime of brush functionalization impacts a 50 nm
      polymer brush layer and decreases the pseudo-first-order rate by a constant
      diffusion-limited factor of 0.233.

PMID- 23009189
TI  - Study protocol: a randomised controlled trial of the effects of a multi-modal
      exercise program on cognition and physical functioning in older women.
AB  - BACKGROUND: Intervention studies testing the efficacy of cardiorespiratory
      exercise have shown some promise in terms of improving cognitive function in
      later life. Recent developments suggest that a multi-modal exercise intervention
      that includes motor as well as physical training and requires sustained attention
      and concentration, may better elicit the actual potency of exercise to enhance
      cognitive performance. This study will test the effect of a multi-modal exercise
      program, for older women, on cognitive and physical functioning. METHODS/DESIGN:
      This randomised controlled trial involves community dwelling women, without
      cognitive impairment, aged 65-75 years. Participants are randomised to exercise
      intervention or non-exercise control groups, for 16 weeks. The intervention
      consists of twice weekly, 60 minute, exercise classes incorporating aerobic,
      strength, balance, flexibility, co-ordination and agility training. Primary
      outcomes are measures of cognitive function and secondary outcomes include
      physical functioning and a neurocognitive biomarker (brain derived neurotrophic
      factor). Measures are taken at baseline and 16 weeks later and qualitative data
      related to the experience and acceptability of the program are collected from a
      sub-sample of the intervention group. DISCUSSION: If this randomised controlled
      trial demonstrates that multimodal exercise (that includes motor fitness
      training) can improve cognitive performance in later life, the benefits will be
      two-fold. First, an inexpensive, effective strategy will have been developed that
      could ameliorate the increased prevalence of age-related cognitive impairment
      predicted to accompany population ageing. Second, more robust evidence will have
      been provided about the mechanisms that link exercise to cognitive improvement
      allowing future research to be better focused and potentially more productive.
      TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registration
      Number: ANZCTR12612000451808.

PMID- 23009190
TI  - Blue light (470 nm) effectively inhibits bacterial and fungal growth.
AB  - Blue light (470 nm) LED antimicrobial properties were studied alone against
      bacteria and with or without the food grade photosensitizer, erythrosine (ERY)
      against filamentous fungi. Leuconostoc mesenteroides (LM), Bacillus atrophaeus
      (BA) or Pseudomonas aeruginosa (PA) aliquots were exposed on nutrient agar plates
      to Array 1 (AR1, 0.2 mW cm(-2)) or Array 2 (AR2, 80 mW cm(-2)), which emitted
      impure or pure blue light (0-300 J cm(-2)), respectively. Inoculated control
      (room light only) plates were incubated (48 h) and colonies enumerated. The
      antifungal properties of blue light combined with ERY (11.4 and 22.8 MUmol l(-1))
      on Penicillium digitatum (PD) and Fusarium graminearum (FG) conidia were
      determined. Conidial controls consisted of: no light, room light-treated conidia
      and ERY plus room light. Light-treated (ERY + blue light) conidial samples were
      exposed only to AR2 (0-100 J cm(-2)), aliquots spread on potato dextrose agar
      plates, incubated (48 h, 30 degrees C) and colonies counted. Blue light alone
      significantly reduced bacterial and FG viability. Combined with ERY, it
      significantly reduced PD viability. Blue light is lethal to bacteria and
      filamentous fungi although effectiveness is dependent on light purity, energy
      levels and microbial genus. SIGNIFICANCE AND IMPACT OF THE STUDY: Light from two
      arrays of different blue LEDs significantly reduced bacterial (Leuconostoc
      mesenteroides, Bacillus atrophaeus and Pseudomonas aeruginosa) viabilities.
      Significant in vitro viability loss was observed for the filamentous fungi,
      Penicillium digitatum and Fusarium graminearum when exposed to pure blue light
      only plus a photosensitizer. F. graminearum viability was significantly reduced
      by blue light alone. Results suggest that (i) the amount of significant loss in
      bacterial viability observed for blue light that is pure or with traces of other
      wavelengths is genus dependent and (ii) depending on fungal genera, pure blue
      light is fungicidal with or without a photosensitizer.

PMID- 23009191
TI  - Addressing the barriers to accessing therapy services in rural and remote areas.
AB  - PURPOSE: Throughout the world, people with a disability who live in rural and
      remote areas experience difficulty accessing a range of community-based services
      including speech-, physio- and occupational therapy. This paper draws on
      information gathered from carers and adults with a disability living in a rural
      area in New South Wales (NSW), Australia to determine the extent to which people
      living in rural areas may receive a person-centred therapy service. METHODS: As
      part of a larger study in rural NSW into the delivery of therapy services, focus
      groups and individual interviews were conducted with 78 carers and 10 adults with
      a disability. Data were analysed using constant comparison and thematic analysis.
      RESULTS: Three related themes emerged: (i) travelling to access therapy; (ii)
      waiting a long time to get therapy; and (iii) limited access to therapy past
      early childhood. The themes overlaid the problems of recruiting and retaining
      sufficient therapists to work in rural areas. CONCLUSIONS: Community-based
      rehabilitation principles offer possibilities for increasing person-centred
      therapy services. We propose a person-centred and place-based approach that
      builds on existing service delivery models in the region and involves four inter
      related strategies aimed at reducing travel and waiting times and with
      applicability across the life course. IMPLICATIONS FOR REHABILITATION: Therapy
      service delivery in rural and remote areas requires: Place-based and person
      centred strategies to build local capacity in communities. Responsive outreach
      programs working with individuals and local communities. Recognition of the need
      to support families who must travel to access remotely located specialist
      services. Innovative use of technology to supplement and enhance service
      delivery.

PMID- 23009192
TI  - Lower limb mechanical properties: determining factors and implications for
      performance.
AB  - Limb stiffness or musculotendinous stiffness (MTS) has previously been examined
      in relation to performance and characterized using a number of different methods.
      However, the fact that MTS shows only low to moderate correlations to
      performances may indicate a lack of understanding of this parameter. In addition
      to this, variation is seen between studies examining the same factors. To date,
      our understanding of MTS and its components are not complete and thus it is
      unclear which characteristic value represents the ideal index of stiffness as it
      relates to performance. Moreover, it is uncertain how MTS stiffness as a
      functional measure relates to performance, and also if there is an optimal amount
      of MTS stiffness for specific functions or tasks. The knowledge of the interplay
      of MTU stiffness as it relates to performance and injury risk is also poorly
      understood in that there is likely a disparity between levels of stiffness
      required to optimize performance and those required to minimize injury risk. The
      aim of this article is to review the literature as it describes the components of
      MTS and to discuss these in terms of their relationship to functional
      performance; consider adaptations of the MTU with training along with associated
      performance changes; highlight and discuss how stiffness may affect loading of
      the soft and bony tissues in terms of the MTU components and gender, with respect
      to risk of injury; discuss the apparent differences in the literature regarding
      associations of the various forms of stiffness index to function; suggest
      recommendations for training in light of adaptation of the muscle and tendon and
      injury risk in context of gender; and, finally, to highlight potential
      limitations of current methodologies and suggest further work to gain insight
      into the mechanisms of stiffness. It is hoped that by suggesting future work, a
      more detailed and comprehensive understanding of MTS will be gained, thus
      enabling appropriate interventions to optimally modify this parameter for
      specific requirements.

PMID- 23009193
TI  - A prospective, randomized, placebo-controlled, double-blind trial about safety
      and efficacy of combined treatment with alteplase (rt-PA) and Cerebrolysin in
      acute ischaemic hemispheric stroke.
AB  - BACKGROUND: The neurotrophic drug Cerebrolysin accelerated recovery and prevented
      acute neuronal damage in preclinical models of ischaemia. Previous clinical
      trials support therapeutic effects in stroke patients. The study investigated
      whether the combination with alteplase and Cerebrolysin is safe and can further
      reduce disability after acute ischaemic stroke. METHODS: This placebo-controlled,
      double-blind trial involved 119 patients with acute ischaemic hemispheric stroke,
      randomly assigned to a combined treatment with alteplase plus Cerebrolysin or
      placebo (administered 1 h after thrombolytic treatment) starting within three
      hours after onset of symptoms. A daily i.v. infusion of 30 ml Cerebrolysin or
      placebo was given for 10 consecutive days. Primary outcome was the modified
      Rankin Scale at day 90. A sequential design with interim analyses was applied.
      RESULTS: The third interim analysis did not show a benefit in the modified Rankin
      Scale for Cerebrolysin on day 90 compared to placebo and the study was stopped.
      The National Institutes of Health Stroke Scale responder analysis (secondary
      outcome measure) showed significantly more patients with an improvement of 6 or
      more points (or a total score of 0 or 1) after two-, five-, 10, and 30 days in
      the Cerebrolysin group. Similar trends were observed for the modified Rankin
      Scale responder analysis without achieving statistical significance. There was no
      difference between treatment groups regarding adverse events. CONCLUSIONS: The
      combination of Cerebrolysin with recombinant tissue-Plasminogen Activator is safe
      for treatment of acute ischaemic stroke but did not improve outcome at day 90.
      During the treatment period with Cerebrolysin (10 days), significantly more
      patients had a favourable response in neurological outcome measures (National
      Institutes of Health Stroke Scale) as compared to the placebo group.

PMID- 23009194
TI  - Equine multinodular pulmonary fibrosis in association with asinine herpesvirus
      type 5 and equine herpesvirus type 5: a case report.
AB  - A standardbred gelding with a history of 10 days pyrexia and lethargy was
      referred to the Equine Hospital at the Swedish University of Agricultural
      Sciences in Uppsala, Sweden.The horse had tachypnea with increased respiratory
      effort and was in thin body condition. Laboratory findings included leukocytosis,
      hyperfibrinogenemia and hypoxemia. Thoracic radiographs showed signs of pneumonia
      with a multifocal nodular pattern, which in combination with lung biopsy findings
      indicated Equine Multinodular Pulmonary Fibrosis (EMPF). EMPF is a recently
      described disease in adult horses with clinical signs of fever, weight loss and
      respiratory problems. The pathological findings include loss of functional
      pulmonary parenchyma due to extensive nodular interstitial fibrosis which has
      been related to infection with the equine herpesvirus type 5 (EHV-5). In this
      case, lung biopsy and tracheal wash samples tested positive for both asinine
      herpesvirus type 5 (AHV-5) and EHV-5 using PCR assays. The horse failed to
      respond to treatment and was euthanized for humane reasons. Postmortem
      examination confirmed the diagnosis of EMPF. This case suggests that not only EHV
      5 alone should be considered in association with the development of this disease.

PMID- 23009195
TI  - Immunoreactivities of androgen receptor, estrogen receptors, p450arom, p450c17
      proteins in wild ground squirrels ovaries during the nonbreeding and breeding
      seasons.
AB  - The aim of this study was to elucidate the regulatory role of androgen in the
      follicular development of wild female ground squirrels. Immunohistochemical
      staining of FSHR, LHR, P450c17, P450arom, androgen receptor (AR), estrogen
      receptors (ERa and ERb) were executed in ovaries of female ground squirrels from
      both breeding and nonbreeding seasons. In addition, total ovarian proteins were
      extracted from the ovaries of squirrels from breeding and nonbreeding seasons,
      and Western blot analysis were performed in order to probe for FSHR, LHR,
      P450c17, P450arom, AR, ERa and ERb. The results of immunohistochemical staining
      and Western blotting of P450c17 showed that there was no significant difference
      between the breeding and nonbreeding seasons. It was found that granulosa cells
      expressed P450arom during the breeding season. In contrast, there was no positive
      staining of P450arom in the nonbreeding season. There was no significant
      difference in immunoreactivity of AR between the breeding and nonbreeding
      seasons. However, the immunoreactivities of ERa and ERb were both significantly
      reduced in the nonbreeding season compared to the breeding season. The positive
      stains of FSHR and LHR were found in the granulosa cells and theca cells of the
      ovaries of the breeding and nonbreeding seasons. In addition, the Western
      blotting results of FSHR and LHR showed a significant reduction in the
      nonbreeding season compared with the breeding season. These findings suggested
      that androgen might be predominantly converted into estrogen in order to regulate
      the follicular development via binding of estrogen receptors during the breeding
      season, whereas androgen might predominantly directly bind androgen receptor to
      regulate the follicular development during the nonbreeding season in the ovaries
      of wild female ground squirrels.

PMID- 23009196
TI  - An analysis of Hall mobility in as-grown and annealed n- and p-type modulation
      doped GaInNAs/GaAs quantum wells.
AB  - In this study, we investigate the effect of annealing and nitrogen amount on
      electronic transport properties in n- and p-type-doped Ga0.68In0.32NyAs1 - y/GaAs
      quantum well (QW) structures with y = 0%, 0.9%, 1.2%, 1.7%. The samples are
      thermal annealed at 700 degrees C for 60 and 600 s, and Hall effect measurements
      have been performed between 10 and 300 K. Drastic decrease is observed in the
      electron mobility of n-type N-containing samples due to the possible N-induced
      scattering mechanisms and increasing effect mass of the alloy. The temperature
      dependence of electron mobility has an almost temperature insensitive
      characteristic, whereas for p-type samples hole mobility is decreased drastically
      at T > 120 K. As N concentration is increased, the hole mobility also increased
      as a reason of decreasing lattice mismatch. Screening effect of N-related alloy
      scattering over phonon scattering in n-type samples may be the reason of the
      temperature-insensitive electron mobility. At low temperature regime, hole
      mobility is higher than electron mobility by a factor of 3 to 4. However, at high
      temperatures (T > 120 K), the mobility of p-type samples is restricted by the
      scattering of the optical phonons. Because the valance band discontinuity is
      smaller compared to the conduction band, thermionic transport of holes from QW to
      the barrier material, GaAs, also contributes to the mobility at high temperatures
      that results in a decrease in mobility. The hole mobility results of as-grown
      samples do not show a systematic behavior, while annealed samples do, depending
      on N concentration. Thermal annealing does not show a significant improvement of
      electron mobility.

PMID- 23009197
TI  - Remission of de novo membranous nephropathy in a kidney allograft recipient: a
      case report.
AB  - Membranous nephropathy (MN), one of the most frequent causes of nephrotic
      syndrome in native kidneys, is also a common glomerular pathology in transplanted
      kidneys(Davison AM, Johnston PA. Allograft membranous nephropathy, Nephrol Dial
      Transplant, 1992;7(Suppl. 1):114-118. Specific treatment modalities have not been
      described for this population. However, renal transplanted patients presented
      with MN could have spontaneous remission as those with idiopathic MN. Here, we
      report a kidney allograft recipient diagnosed with de novo MN in early phases of
      posttransplantation period having a clinical remission over months.

PMID- 23009198
TI  - Differences in the risk factors of reflux esophagitis according to age in Korea.
AB  - The prevalence of gastroesophageal reflux disease in Korea has been believed to
      be low, but the incidence of gastroesophageal reflux disease in Korea is expected
      to increase because of the longer life expectancy and more ingestion of
      westernized food. The aim of this study was to report differences in the risk
      factors of reflux esophagitis (RE) according to age in Korea. We prospectively
      recruited the subjects who had RE among those who visited a health promotion
      center for upper gastrointestinal cancer surveillance at Hallym Medical Center
      (five institutions) between January 2008 and February 2009. The enrolled study
      participants comprised 742 subjects with RE and 1484 healthy controls. The
      independent risk factors of RE in young and adult group were male sex, smoking,
      coffee, body mass index >= 25, hiatal hernia, and Helicobacter pylori negativity.
      The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia.
      The risk factors for RE according to age group were found to differ. In elderly
      group, Helicobacter pylori infection was not a significant protective factor
      contrary to young and adult groups. 

PMID- 23009199
TI  - Origin of long-range ferromagnetic ordering in metal-organic frameworks with
      antiferromagnetic dimeric-Cu(II) building units.
AB  - Even though metal-organic frameworks (MOFs) derived from antiferromagnetic
      dimeric-Cu(II) building units and nonmagnetic molecular linkers are known to
      exhibit unexpected ferromagnetic behavior, a comprehensive understanding of the
      underlying mechanism remains elusive. Using a combined theoretical and
      experimental approach, here we reveal the origin of the long-range ferromagnetic
      coupling in a series of MOFs, constructed from antiferromagnetic dimeric-Cu(II)
      building blocks. Our studies show that the strong localization of copper vacancy
      states favors spontaneous spin polarization and formation of local moment. These
      copper vacancy-induced moments are coupled via the itinerant electrons in the
      conjugated aromatic linkers to establish a long-range ferromagnetic ordering. The
      proposed mechanism is supported by direct experimental evidence of copper
      vacancies and the magnetic hysteresis (M-H) loops.

PMID- 23009200
TI  - Low-temperature fabrication of Au-Co cluster mixed nanohybrids with high magnetic
      moment of Co.
AB  - In recent years, the synergistic effects of Au-based hybrids have generated
      enormous scientific interest. The hybrids of Au and Co are expected to exhibit
      attractive properties. In this paper, we report the successful fabrication of the
      nanohybrids between bulk-immiscible Au and Co with chain-like structures via a
      mild solution method. Elemental mapping, XRD and EXAFS data reveal that the as
      prepared AuCo nanohybrids might be of cluster mixed configuration. A sequential
      redox and imperfection-promoted aggregation/diffusion process is proposed to
      elucidate the formation mechanism of the nanohybrids. The as-prepared products
      exhibit a temperature-independent saturation magnetization with the magnetic
      moment of Co as high as ~2.95 MU(B) for each Co atom at 300 K, much higher than
      the bulk value (~1.7 MU(B) for each Co atom) and approaching the theoretical
      value of an atomic Co (~3.0 MU(B) for each Co atom).

PMID- 23009201
TI  - Splenocyte apoptosis in Plasmodium berghei ANKA infection: possible role of TNF
      alpha and TGF-beta.
AB  - Cerebral malaria is associated with the circulating levels of tumour necrosis
      factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), but
      association between these two cytokines and implications in splenocyte apoptosis
      remain largely obscured. We have evaluated the outcome of TGF-beta and TNF-alpha
      production in the context of splenocyte apoptosis during Plasmodium berghei ANKA
      (PbA) infection. Blood-stage PbA infection confirmed blood-brain barrier
      disruption, disarray of white pulp, increase in percentage of sub-G0/G1 and
      splenocyte apoptosis. Flow cytometric analysis reveals up-regulation of Fas-L
      followed by caspase-8 and caspase-3 activation and signifies possible involvement
      of Fas-L-mediated splenocyte apoptosis. We have observed down-regulation of TGF
      beta and up-regulation of TNF-alpha in tissue and serum level, respectively,
      during PbA infection. Association between the production of TGF-beta and the
      severity of malaria infection in splenocytes was verified with TGF-beta inhibitor
      that exacerbated the apoptotic process. In contrary, TNF-alpha inhibitor causes
      significant delay in apoptotic process, but could not alter the lethality of
      parasite. Thus, results from this study suggest that the critical balance between
      TGF-beta and TNF-alpha might have a key role on Fas-L-mediated splenocyte
      apoptosis during experimental cerebral malaria.

PMID- 23009202
TI  - Client characteristics and acceptability of a home-based HIV counselling and
      testing intervention in rural South Africa.
AB  - BACKGROUND: HIV counselling and testing (HCT) is a critical gateway for
      addressing HIV prevention and linking people to treatment, care, and support.
      Since national testing rates are often less than optimal, there is growing
      interest in expanding testing coverage through the implementation of innovative
      models such as home-based HIV counselling and testing (HBHCT). With the aim of
      informing scale up, this paper discusses client characteristics and acceptability
      of an HBHCT intervention implemented in rural South Africa. METHODS: Trained lay
      counsellors offered door-to-door rapid HIV testing in a rural sub-district of
      KwaZulu-Natal, South Africa. Household and client data were captured on cellular
      phones and transmitted to a web-based data management system. Descriptive
      analysis was undertaken to examine client characteristics, testing history, HBHCT
      uptake, and reasons for refusal. Chi-square tests were performed to assess the
      association between client characteristics and uptake. RESULTS: Lay counsellors
      visited 3,328 households and tested 75% (5,086) of the 6,757 people met. The
      majority of testers (73.7%) were female, and 57% had never previously tested.
      With regard to marital status, 1,916 (37.7%), 2,123 (41.7%), and 818 (16.1%) were
      single, married, and widowed, respectively. Testers ranged in age from 14 to 98
      years, with a median of 37 years. Two hundred and twenty-nine couples received
      couples counselling and testing; 87.8%, 4.8%, and 7.4% were concordant negative,
      concordant positive, and discordant, respectively. There were significant
      differences in characteristics between testers and non-testers as well as between
      male and female testers. The most common reasons for not testing were: not being
      ready/feeling scared/needing to think about it (34.1%); knowing his/her status
      (22.6%), being HIV-positive (18.5%), and not feeling at risk of having or
      acquiring HIV (10.1%). The distribution of reasons for refusal differed
      significantly by gender and age. CONCLUSIONS: These findings indicate that HBHCT
      is acceptable in rural South Africa. However, future HBHCT programmes should
      carefully consider community context, develop strategies to reach a broad range
      of clients, and tailor intervention messages and services to meet the unique
      needs of different sub-groups. It will also be important to understand and
      address factors related to refusal of testing.

PMID- 23009204
TI  - Thermal effects of a combined irrigation method during implant site drilling. A
      standardized in vitro study using a bovine rib model.
AB  - OBJECTIVES: The purpose of this study was to evaluate the temperature changes
      during implant osteotomies with a combined irrigation system as compared to the
      commonly used external and internal irrigation under standardized conditions.
      MATERIAL AND METHODS: Drilling procedures were performed on VII bovine ribs using
      a computer-aided surgical system that ensured automated intermittent drilling
      cycles to simulate clinical conditions. A total of 320 drilling osteotomies were
      performed with twist (2 mm) and conical implant drills (3.5/4.3/5 mm) at various
      drilling depths (10/16 mm) and with different saline irrigation (50 ml/min)
      methods (without/external/internal/combined). Temperature changes were recorded
      in real time by two custom-built thermoprobes with 14 temperature sensors (7
      sensors/thermoprobe) at defined measuring depths. RESULTS: The highest
      temperature increase during osteotomies was observed without any coolant
      irrigation (median, 8.01 degrees C), followed by commonly used external saline
      irrigation (median, 2.60 degrees C), combined irrigation (median, 1.51 degrees C)
      and ultimately with internal saline irrigation (median, 1.48 degrees C).
      Temperature increase with different drill diameters showed significant
      differences (P < 0.05) regarding drill depth, confirming drill depth and time of
      drilling as influencing factors of heat generation. Internal saline irrigation
      showed a significantly smaller temperature increase (P < 0.05) compared with
      combined and external irrigation. A combined irrigation procedure appears to be
      preferable (P < 0.05) to an external irrigation method primarily with higher
      osteotomy depths. CONCLUSIONS: Combined irrigation provides sufficient reduction
      in temperature changes during drilling, and it may be more beneficial in deeper
      site osteotomies. Further studies to optimize the effects of a combined
      irrigation are needed.

PMID- 23009203
TI  - Selective histone deacetylase 6 inhibitors bearing substituted urea linkers
      inhibit melanoma cell growth.
AB  - The incidence of malignant melanoma has dramatically increased in recent years
      thus requiring the need for improved therapeutic strategies. In our efforts to
      design selective histone deactylase inhibitors (HDACI), we discovered that the
      aryl urea 1 is a modestly potent yet nonselective inhibitor. Structure-activity
      relationship studies revealed that adding substituents to the nitrogen atom of
      the urea so as to generate compounds bearing a branched linker group results in
      increased potency and selectivity for HDAC6. Compound 5 g shows low nanomolar
      inhibitory potency against HDAC6 and a selectivity of ~600-fold relative to the
      inhibition of HDAC1. These HDACIs were evaluated for their ability to inhibit the
      growth of B16 melanoma cells with the most potent and selective HDAC6I being
      found to decrease tumor cell growth. To the best of our knowledge, this work
      constitutes the first report of HDAC6-selective inhibitors that possess
      antiproliferative effects against melanoma cells.

PMID- 23009205
TI  - Object habituation in horses: the effect of voluntary versus negatively
      reinforced approach to frightening stimuli.
AB  - REASONS FOR PERFORMING THE STUDY: The ability of horses to habituate to novel
      objects influences safety in the horse-human relationship. However, the
      effectiveness of different habituation techniques has not been investigated in
      detail. OBJECTIVES: 1) To investigate whether horses show increased stress
      responses when negatively reinforced to approach novel objects, compared with
      horses allowed to voluntarily explore the objects and 2) whether a negatively
      reinforced approach facilitates object habituation. METHODS: Twenty-two 2-3-year
      old Danish Warmblood geldings were included. Half of the horses (NR group) were
      negatively reinforced by a familiar human handler to approach a collection of
      novel objects in a test arena. The other half were individually released in the
      arena and were free to explore the objects (VOL group). On the next day, the
      horses were exposed to the objects again without a human handler, to investigate
      the rate of habituation. Behavioural and heart rate responses were recorded.
      RESULTS: All VOL horses initially avoided the unknown objects, whereas the
      handler was able to get all NR horses to approach and stand next to the objects
      within the first 2 min session. The NR horses had a significantly longer duration
      of alertness and a higher max heart rate in the first session. On the next day,
      however, NR horses spent significantly less time investigating the objects and
      had a shorter latency to approach a feed container, placed next to the objects,
      indicating increased habituation. CONCLUSION: A negatively reinforced approach to
      novel objects increases stress responses during the initial exposure but
      facilitates habituation in young horses. POTENTIAL RELEVANCE: Although a
      negatively reinforced approach appears beneficial for habituation, the procedure
      should be carefully managed due to increased stress responses in the horse, which
      may constitute a safety risk. Further experiments should aim to investigate
      differences in stimulus intensity.

PMID- 23009207
TI  - Dynamic effects on containment of air-curtain fume hood operated with heat
      source.
AB  - This study focused on the leakage characteristics of the air-curtain fume hood
      that are subject to the influences of sash movement and walk-by motion while a
      high temperature heat source was operated in the hood. The flow visualization and
      trace gas test method were used to investigate the performance of the air-curtain
      fume hood. An electric heater was placed in the hood to simulate the heat source.
      The temperature of the heat source installed inside the air-curtain fume hood
      varied between 180 degrees C and 300 degrees C. Trace gas tests following the
      dynamic test methods of EN-14175 protocol were employed to measure the spillages
      of sulfur hexafluoride gas that were released in the hood. When subject to the
      influence of sash movement at a heat source temperature lower than 260 degrees C,
      the leakage level was high at the suction velocity V(s) < 8 m/sec but was
      negligibly small at V(s) > 10 m/sec. When subject to the influence of people walk
      by, the leakage level was relatively low at the suction velocity larger than 8
      m/sec at sash height H = 50 cm. The height of the sash opening was a crucial
      parameter for the containment of the air-curtain fume hood. At the sash opening
      lower than about 25 cm, suction velocity less than or equal to 6 m/sec was enough
      to make the sulfur hexafluoride leakage less than the threshold value, 0.65 ppm,
      suggested by the BG Chemie. The air-curtain fume hood presented a great
      performance to resist the effect of drafts even though there was a high
      temperature heat source working in the hood.

PMID- 23009206
TI  - The role of mediastinal adipose tissue 11beta-hydroxysteroid d ehydrogenase type
      1 and glucocorticoid expression in the development of coronary atherosclerosis in
      obese patients with ischemic heart disease.
AB  - BACKGROUND: Visceral fat deposition and its associated atherogenic complications
      are mediated by glucocorticoids. Cardiac visceral fat comprises mediastinal
      adipose tissue (MAT) and epicardial adipose tissue (EAT), and MAT is a potential
      biomarker of risk for obese patients. AIM: Our objective was to evaluate the role
      of EAT and MAT 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) and
      glucocorticoid receptor (GCR) expression in comparison with subcutaneous adipose
      tissue (SAT) in the development of coronary atherosclerosis in obese patients
      with coronary artery disease (CAD), and to assess their correlations with CD68
      and fatty acids from these tissues. METHODS AND RESULTS: Expression of 11beta-HSD
      1 and GCR was measured by qRT-PCR in EAT, MAT and SAT of thirty-one obese
      patients undergoing coronary artery bypass grafting due to CAD (obese CAD group)
      and sixteen obese patients without CAD undergoing heart valve surgery (controls).
      11beta-HSD-1 and GCR expression in MAT were found to be significantly increased
      in the obese CAD group compared with controls (p < 0.05). In the obese CAD group,
      11beta-HSD-1 and GCR mRNA levels were strongly correlated in MAT. Stearidonic
      acid was significantly increased in EAT and MAT of the obese CAD group and
      arachidonic acid was significantly expressed in MAT of the obese male CAD group
      (p < 0.05). CONCLUSIONS: We report for the first time the increased expression of
      11beta-HSD-1 and GCR in MAT compared with EAT and SAT, and also describe the
      interrelated effects of stearidonic acid, HOMA-IR, plasma cortisol and GCR mRNA
      levels, explaining 40.2% of the variance in 11beta-HSD-1 mRNA levels in MAT of
      obese CAD patients. These findings support the hypothesis that MAT contributes
      locally to the development of coronary atherosclerosis via glucocorticoid action.

PMID- 23009208
TI  - The connecticut experiment: the role of ultrasound in the screening of women with
      dense breasts.
AB  - The aim of this study was to determine the potential of screening breast
      ultrasound to improve breast cancer detection in women with mammographically
      normal, but dense breasts. Six Connecticut radiology practices with 12 total
      sites participated in a retrospective chart review. The total number of screening
      mammograms, screening ultrasounds broken down by BIRADS (Breast Imaging Reporting
      and Data System) codes, and the number of positive and negative biopsies were
      collected from November 2009 through November 2010. Demographic data on the
      patients with positive biopsies as well as cancer staging were also collected.
      Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive
      Value were calculated. A total of 72,030 screening mammograms and 8,647 screening
      ultrasounds were performed at the research sites during the study period.
      Relevant research indicates that 41% of the female population has dense breasts.
      In this study, 12% (8,647/72,030) underwent follow-up breast ultrasound
      screening. A total of 86% (7,451/8,647) of the ultrasounds were BIRADS 1 or 2, 9%
      (767/8,647) were BIRADS 3, 5% (429/8,647) were BIRADS 4 or 5. Of those 429
      recommended to undergo biopsy 418 were performed and 28 cancers were found. There
      was one false negative. Screening breast ultrasound in women with
      mammographically normal, but dense breasts has a Positive Predictive Value (PPV)
      of 6.7% (28/418), Negative Predictive Value (NPV) of 99.9% (7,450/7,451),
      sensitivity of 96.6% (28/29), and a specificity of 94.9% (7,450/7,851). Screening
      ultrasound had an additional yield of 3.25 per 1,000 cancers in women with dense
      breasts and normal mammograms and no additional risk factors. As with all
      screening tests, time, cost, and false positive risk must be considered.

PMID- 23009209
TI  - Reconstruction of infected abdominal wall defects using latissimus dorsi free
      flap.
AB  - INTRODUCTION: Infected abdominal defects are a challenge to surgeons. In this
      study, we describe 10 cases in which the latissimus dorsi myocutaneous flap was
      used for successful reconstruction of abdominal wall defects severely infected
      with methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Retrospective
      review of 10 patients with abdominal wall defects that were reconstructed using
      the latissimus dorsi myocutaneous flap between 2002 and 2010. All patients had
      abdominal defects with hernias, combined with MRSA infections. The sizes of the
      flaps ranged from 120 to 364 cm(2) . The deep inferior epigastric artery was the
      recipient vessel in nine patients and the internal mammary vessels were used for
      one patient. RESULTS: There were no complications relating to the flaps, although
      there were other minor complications including wound dehiscence, haematoma and
      fluid correction. After reconstruction, there were no signs of infection during
      follow-up periods, and the patients were satisfied with the final results.
      CONCLUSION: Reconstruction using the latissimus dorsi myocutaneous flap,
      including muscle fascia structures, is a potential treatment option for severely
      infected large abdominal wall defects.

PMID- 23009210
TI  - Understanding the quenching effects of aromatic C-H- and C-D-oscillators in near
      IR lanthanoid luminescence.
AB  - Several series of selectively deuterated 2,2'-bipyridine-based cryptates with the
      near-IR emissive lanthanoids Pr, Nd, Er, and Yb are reported. The structural and
      luminescence properties of these complexes have been comprehensively
      investigated. A combination of experimental techniques (X-ray crystallography,
      lanthanoid-induced NMR shift analysis, luminescence, vibrational near-IR
      absorption) and theoretical concepts has been applied with a focus on
      nonradiative deactivation through multiphonon relaxation of lanthanoid excited
      states by aromatic, high-energy C-(H/D) oscillators. It is shown that the
      characteristics for the overtones of these vibrational modes deviate
      substantially from harmonic oscillators and that anharmonicity within a local
      mode Morse model is an essential parameter for any accurate description. The
      spectral overlap integrals (SOIs) of lanthanoid electronic states with aromatic C
      (H/D) overtones are evaluated quantitatively for different lanthanoid/oscillator
      combinations and the implications for luminescence enhancement through
      deuteration is discussed. Simple Gaussian functions are proposed as appropriate
      mathematical forms for the empirical approximation of SOIs.

PMID- 23009211
TI  - Tailoring the pore sizes of microporous pillared interlayered clays through layer
      charge reduction.
AB  - A F-rich potassium hectorite,
      [K(0.48(2))](inter)[Mg(2.54(8))Li(0.43)](oct)[Si(4)](tet)O(10)F(2), with a layer
      charge of x = 0.48 per formula unit (pfu) was synthesized by high temperature
      melt synthesis. After Mg-exchange, the layer charge could be reduced
      significantly post synthesis by annealing (250  degrees C) as confirmed by
      alkylammonium exchange and cation exchange capacity. By pillaring this new low
      charge material with Me(2)DABCO(2+) (N,N-dimethyl-1,1-diazabicyclo [2.2.2]octane
      dication) and Rh(bpy)(3)(3+) (rhodium-tris-2,2'-bipyridin trication), we observed
      a remarkable increase in micropore volume and pore diameter by Ar/Ar(l)
      physisorption measurements. This method allows the tailoring of pore sizes of
      pillared clays by reducing the layer charge and consequently the pillar density.

PMID- 23009212
TI  - Intensive physiotherapy for vegetative and minimally conscious state patients: a
      retrospective audit and analysis of therapy intervention.
AB  - PURPOSE: To analyse physiotherapy interventions and evaluate their effectiveness
      in the prevention and management of contracture with patients admitted in either
      vegetative or minimally conscious state in a UK Inpatient Regional Acquired Brain
      Injury Rehabilitation Service. METHOD: Retrospective audit of dependency levels
      and physiotherapy interventions in ten vegetative or minimally conscious state
      patients admitted over a 3-year period (2006-2009). Admission and discharge
      patient dependency status, Wessex Head Injury Matrix data and passive range of
      movement measurements on admission and discharge from physiotherapy were
      recorded. RESULTS: All patients presented with hypertonicity including
      contractures and all initially received a manual stretching/passive movement
      programme. Casting/splinting was employed in 8 cases and 7 received botulinum
      toxin injections. Standing regimes were initiated for 8 patients. No patient
      emerged out of either vegetative or minimally conscious state. Although they
      remained fully dependent for care needs, carer burden was reduced and all
      patients were able sustain a seating regimen. No minimal clinically important
      difference was observed in 85 out of 120 joint ranges measured (70.8%). Positive
      outcomes were observed in only 14 joints (11.7%) and negative outcomes in 21
      joints (17.5%). CONCLUSION: At present, there is a paucity of evidence regarding
      physiotherapy efficacy to inform the management of patients in vegetative or
      minimally conscious state. Clearer agreed definitions of clinically important
      difference in passive range of movement are required to allow better
      interpretation of outcomes. Interventions should be aimed at minimising carer
      burden and developing individualised disability management programmes. Further
      research documenting the long-term outcomes in such patients is warranted.

PMID- 23009213
TI  - Highly fluorescent graphene oxide-poly(vinyl alcohol) hybrid: an effective
      material for specific Au3+ ion sensors.
AB  - We have developed a new highly fluorescent graphene oxide (GO)/poly(vinyl
      alcohol) (PVA) hybrid (GO-PVA) in an acidic medium (pH 4). Fourier transform
      infrared (FTIR) spectra indicate the formation of hydrogen bonds between the
      hydroxy group of PVA and the hydroxy groups of GO. The hybrid is highly
      fluorescent, because of passivation by hydrogen bonding, as evident from Raman
      spectra. The quantum yields of GO-PVA hybrids are higher than that of GO. The
      fluorescent microscopic images of the hybrids exhibit a fibrillar morphology, and
      all of them emit highly intense green light. Field-emission scanning electron
      microscopy (FESEM) micrographs also show a fibrillar morphology, which is
      produced due to the supramolecular organization of GO-PVA complex. The highly
      fluorescent GO-PVA1 hybrid has been used as a fascinating tool for selective
      sensing of Au(3+) ions in aqueous media with a detectable limit of ~275 ppb. The
      sensitivity of the Au(3+) ion (300 MUM) in the presence of 600 MUM concentrations
      of each ion (Cu(2+), Ag(+), Mg(2+), Ca(2+), Zn(2+), K(+), Pb(2+), Co(2+), Ni(2+),
      Pd(2+), Fe(2+), Fe(3+), and Cr(3+)), taken together, is unique, exhibiting a
      quenching efficiency of 76%. The quenching efficiency in the presence of a
      biologically analogous mixture (d-glucose, d-lysine, BSA, Na(+), K(+), Ca(2+),
      Mg(2+), Zn(2+)) (600 MUM each) is 73%, which suggests that the GO-PVA1 hybrid is
      an efficient sensor of Au(3+) ions. The average lifetime of GO at pH 4 increases
      in the GO-PVA1 hybrid, indicating the formation of a more stable excited state
      but the increase in lifetime value after addition of Au(3+) salt solution to the
      hybrid solution indicates dynamic quenching. The selectivity of sensing of Au(3+)
      is attributed to its reduction potential being higher than that of other metal
      ions and XPS data of GO-PVA1 hybrid with 300 MUM Au(3+) substantiate the
      reduction of Au(3+) to Au(0), because of the transfer of excitons from the hybrid
      facilitating the selective photoluminescence (PL) quenching.

PMID- 23009216
TI  - Surfactant-controlled polymerization of semiconductor clusters to quantum dots
      through competing step-growth and living chain-growth mechanisms.
AB  - This article reports control of the competition between step-growth and living
      chain-growth polymerization mechanisms in the formation of cadmium chalcogenide
      colloidal quantum dots (QDs) from CdSe(S) clusters by varying the concentration
      of anionic surfactant in the synthetic reaction mixture. The growth of the
      particles proceeds by step-addition from initially nucleated clusters in the
      absence of excess phosphinic or carboxylic acids, which adsorb as their anionic
      conjugate bases, and proceeds indirectly by dissolution of clusters, and
      subsequent chain-addition of monomers to stable clusters (Ostwald ripening) in
      the presence of excess phosphinic or carboxylic acid. Fusion of clusters by step
      growth polymerization is an explanation for the consistent observation of so
      called "magic-sized" clusters in QD growth reactions. Living chain-addition
      (chain addition with no explicit termination step) produces QDs over a larger
      range of sizes with better size dispersity than step-addition. Tuning the molar
      ratio of surfactant to Se(2-)(S(2-)), the limiting ionic reagent, within the
      living chain-addition polymerization allows for stoichiometric control of QD
      radius without relying on reaction time.

PMID- 23009214
TI  - Comparative multi-goal tradeoffs in systems engineering of microbial metabolism.
AB  - BACKGROUND: Metabolic engineering design methodology has evolved from using
      pathway-centric, random and empirical-based methods to using systems-wide,
      rational and integrated computational and experimental approaches. Persistent
      during these advances has been the desire to develop design strategies that
      address multiple simultaneous engineering goals, such as maximizing productivity,
      while minimizing raw material costs. RESULTS: Here, we use constraint-based
      modeling to systematically design multiple combinations of medium compositions
      and gene-deletion strains for three microorganisms (Escherichia coli,
      Saccharomyces cerevisiae, and Shewanella oneidensis) and six industrially
      important byproducts (acetate, D-lactate, hydrogen, ethanol, formate, and
      succinate). We evaluated over 435 million simulated conditions and 36 engineering
      metabolic traits, including product rates, costs, yields and purity. CONCLUSIONS:
      The resulting metabolic phenotypes can be classified into dominant clusters (meta
      phenotypes) for each organism. These meta-phenotypes illustrate global phenotypic
      variation and sensitivities, trade-offs associated with multiple engineering
      goals, and fundamental differences in organism-specific capabilities. Given the
      increasing number of sequenced genomes and corresponding stoichiometric models,
      we envisage that the proposed strategy could be extended to address a growing
      range of biological questions and engineering applications.

PMID- 23009215
TI  - Nasal cytology in children: recent advances.
AB  - Nasal cytology is a very useful diagnostic tool in nasal disorders, being able to
      detect both the cellular modifications of the nasal epithelium caused by either
      allergen exposure or irritative stimuli (that may be physical or chemical, acute
      or chronic), or inflammation. Over these past few years, nasal cytology has
      allowed to identify new disorders, such as the non-allergic rhinitis with
      eosinophils (NARES), the non-allergic rhinitis with mast cells (NARMA), the non
      allergic rhinitis with neutrophils (NARNE), and the non-allergic rhinitis with
      eosinophils and mast cells (NARESMA). The rhinocytogram is actually able to
      distinguish the different forms of allergic rhinitis and to suggest the
      appropriate treatment, such as antinflammatory drugs or allergen immunotherapy.
      The technique is easy to perform and nasal cytology is therefore particularly
      suitable even for children. Such a consideration suggests the utility of a
      systematic use of nasal cytology in the diagnostic work-up of nasal disorders in
      children, in order to reach a proper defined diagnosis and to set a rational
      therapeutic approach: in facts, these two elements are fundamental in order to
      prevent from complications and to improve the patient's quality of life.

PMID- 23009217
TI  - FLT3-driven redox-modulation of Ezrin regulates leukaemic cell migration.
AB  - The concept of reactive oxygen species (ROS) being produced via the activation of
      specific oncogenes provides a basis for generating genomic instability and pro
      survival signalling in tumour cells. The purpose of this study was to identify
      downstream targets of NADPH oxidase (Nox)-derived ROS signalling in acute myeloid
      leukaemia cells, by performing a proteomic analysis utilizing two-dimensional
      phosphotyrosine immunoblotting. The majority of the targets identified were
      cytoskeletal-associated proteins including Ezrin, a known regulator of the
      cytoskeleton, which was examined further. The study demonstrated that inhibition
      of Nox enzymes, using diphenyleneiodonium chloride in the acute myeloid leukaemia
      cell line MOLM-13, resulted in a decrease in Ezrin tyrosine phosphorylation and
      also triggered a shift in Ezrin sub-cellular localization as detected by
      immunofluorescence. The change in Ezrin localization coincided with altered cell
      morphology, observed using scanning electron microscopy and a decreased ability
      to migrate through a polycarbonate transwell membrane. Similar effects were
      observed upon inhibition of the oncogenic receptor tyrosine kinase FLT3 using the
      staurosporine derivate PKC412, implicating a role for FLT3 as an upstream
      regulator of Ezrin. Our results indicate that FLT3 drives production of ROS by
      Nox, which stimulates changes in Ezrin tyrosine phosphorylation and localization
      via redox regulation of Src. Furthermore, inhibition of FLT3 signalling leads to
      alterations in MOLM-13 cell morphology and has a significant influence on cell
      motility.

PMID- 23009218
TI  - Submicron machining and biomolecule immobilization on porous silicon by electron
      beam.
AB  - Three-dimensional submicrometric structures and biomolecular patterns have been
      fabricated on a porous silicon film by an electron beam-based functionalization
      method. The immobilized proteins act as a passivation layer against material
      corrosion in aqueous solutions. The effects' dependence on the main parameters of
      the process (i.e., the electron beam dose, the biomolecule concentration, and the
      incubation time) has been demonstrated.

PMID- 23009219
TI  - Composite lymphoma after chemotherapy with regressed diffuse large B-cell
      lymphoma and transformed cytotoxic T-cell lymphoma.

PMID- 23009220
TI  - Regulatory T-cells in B-cell chronic lymphocytic leukemia: their role in disease
      progression and autoimmune cytopenias.
AB  - Regulatory T-cells (Tregs) have been shown to be important for the balance of
      autoimmunity and oncogenesis. Tregs have a protective role in autoimmune diseases
      and conversely promote oncogenesis. Chronic lymphocytic leukemia (CLL) is unique
      in being at the cross-roads of oncogenesis and autoimmunity. We studied Tregs,
      defined as CD4+CD25(high)CD127(low)FOXP3+, in 32 treatment-naive patients with
      CLL. Our study shows that patients with CLL had a higher absolute Treg count than
      the control group (p < 0.001). A progressive increase of Tregs was noted in
      advanced stages of the disease (p < 0.001). The increase in absolute Treg count
      is more significant than the increase in percentage Tregs. The absolute Treg
      count appears to be more important in disease pathogenesis. The absolute Treg
      count was significantly higher in those patients having autoimmune cytopenias.
      There was an inverse correlation between lymphocyte doubling time and absolute
      Treg count (p = 0.03). The absolute Treg count may be used as a prognostic marker
      in CLL.

PMID- 23009221
TI  - BRAF V600E mutation in adult acute lymphoblastic leukemia.

PMID- 23009222
TI  - Lymphatic mapping with fluorescence navigation using indocyanine green and
      axillary surgery in patients with primary breast cancer.
AB  - The indocyanine green fluorescence (ICGf) navigation method provides real-time
      lymphatic mapping and sentinel lymph node (SLN) visualization, which enables the
      removal of SLNs and their associated lymphatic networks. In this study, we
      investigated the features of the drainage pathways detected with the ICGf
      navigation system and the order of metastasis in axillary nodes. From April 2008
      to February 2010, 145 patients with clinically node-negative breast cancer
      underwent SLN surgery with ICGf navigation. The video-recorded data from 79
      patients were used for lymphatic mapping analysis. We analyzed 145 patients with
      clinically node-negative breast cancer who underwent SLN surgery with the ICGf
      navigation system. Fluorescence-positive SLNs were identified in 144 (99%) of 145
      patients. Both single and multiple routes to the axilla were identified in 47% of
      cases using video-recorded lymphatic mapping data. An internal mammary route was
      detected in 6% of the cases. Skip metastasis to the second or third SLNs was
      observed in 6 of the 28 node-positive patients. We also examined the strategy of
      axillary surgery using the ICGf navigation system. We found that, based on the
      features of nodal involvement, 4-node resection could provide precise information
      on the nodal status. The ICGf navigation system may provide a different lymphatic
      mapping result than computed tomography lymphography in clinically node-negative
      breast cancer patients. Furthermore, it enables the identification of lymph nodes
      that do not accumulate indocyanine green or dye adjacent to the SLNs in the
      sequence of drainage. Knowledge of the order of nodal metastasis as revealed by
      the ICGf system may help to personalize the surgical treatment of axilla in SLN
      positive cases, although additional studies are required.

PMID- 23009223
TI  - Total cholesterol content of erythrocyte membranes is associated with the
      severity of coronary artery disease and the therapeutic effect of rosuvastatin.
AB  - INTRODUCTION: Numerous studies suggest that total cholesterol content of
      erythrocyte membranes (CEM) might play a critical role in atherosclerotic plaque
      progression and instability. However, the exact role of CEM in atherosclerosis
      remains obscure. Our study was designed to investigate the association between
      CEM and the severity of coronary artery disease (CAD), and to assess the effect
      of rosuvastatin on CEM levels. METHODS: CEM levels were assessed in 136
      participants, including acute coronary syndrome (ACS) (non-ST-segment elevation
      ACS (NSTEACS) and ST-segment elevation myocardial infarction (STEMI)), stable
      angina pectoris (SAP), and controls. The Gensini score was used to estimate the
      severity of CAD. Additionally, 54 patients with CAD were medicated with
      rosuvastatin, 5 or 10 mg once daily, and then checked at 6 months. RESULTS: The
      highest level of CEM was found in the STEMI group, followed by the NSTEACS, the
      SAP, and the control groups. Gensini score in group IV (CEM > 141.6 MUg/mg) was
      markedly higher compared with group I (CEM <=77.6 MUg/mg). Gensini scores in
      group II (77.6 < CEM <=111.1 MUg/mg) and group III (111.1 < CEM <=141.6 MUg/mg)
      were also higher than in group I (all P < 0.001). Furthermore, a positive
      correlation was found between CEM levels and Gensini score (r = 0.714, P <
      0.001). CEM levels were dose-dependently reduced by rosuvastatin therapy.
      CONCLUSIONS: CEM levels are positively associated with the severity of CAD,
      meaning that CEM might contribute to the development of CAD. Importantly,
      rosuvastatin could decrease CEM levels in patients with CAD and might effectively
      help to attenuate the progression of CAD.

PMID- 23009225
TI  - A case of metachronous double primary neuroendocrine cancer in pancreas/ileum and
      uterine cervix.
AB  - We describe an unusual case of a 50-year-old female patient developing two
      primary cancers with neuroendocrine features. Initially the patient underwent
      surgery for an entero-pancreatic neuroendocrine carcinoma. During the subsequent
      follow-up she experienced some episodes of vaginal bleeding with negative PET
      scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG). A
      Papanicolaou (pap) smear and an endometrial biopsy revealed a primary
      neuroendocrine cancer of the uterine cervix. The present case underlines the
      importance of clinical follow-up after a diagnosis of intestinal neuroendocrine
      tumor, investigating any new symptom. Female patients, after the diagnosis of
      entero-pancreatic neuroendocrine carcinoma, must be recommended to continue
      screening pap test examinations for the likelihood of classical squamous and
      glandular cervical cancers and also for neuroendocrine cervical cancer.

PMID- 23009226
TI  - Dialysis methods may affect carotid intima-media thickness in Chinese end-stage
      renal disease patients.
AB  - Atherosclerosis is the most common cause of cardiovascular morbidity in end-stage
      renal disease (ESRD) patients and carotid intima-media thickness (IMT) is an
      early independent predictor of atherosclerosis. The aim of this study is to
      compare the continuous ambulatory peritoneal dialysis (CAPD) and the maintenance
      hemodialysis (MHD) for carotid IMT in Chinese ESRD patients. A total of 72 CAPD
      patients, 92 MHD patients, and 50 age- and sex-matched healthy controls were
      included. Dialysis patients were divided into five subgroups according to
      dialysis duration: 3-6, 7-12, 13-59, 60-119, and 120-179 months. Carotid IMT and
      carotid plaques were detected for each patient. The carotid IMT and total plaque
      detection rate in the CAPD and MHD groups were considerably higher than in the
      healthy control group (p < 0.01). No significant difference was found in the
      carotid IMT and total plaque detection rate between the CAPD group and the MHD
      group (p > 0.05). However, after stratification by dialysis duration, the total
      carotid IMT in the CAPD subgroup was higher than in the MHD subgroup in dialysis
      duration of 60-119 and 120-179 months (p < 0.05), and there was no significant
      difference in the total plaque detection rate between the CAPD and MHD subgroups
      in the same dialysis duration (p > 0.05). Our study showed that both CAPD and MHD
      affect carotid IMT in Chinese ESRD patients, and the degree of atherosclerosis in
      CAPD patients might be higher than that in MHD patients after 5 years of
      dialysis.

PMID- 23009224
TI  - Obstructive sleep apnea syndrome (OSAS) and hypertension: pathogenic mechanisms
      and possible therapeutic approaches.
AB  - Obstructive sleep apnea syndrome (OSAS), a chronic condition characterized by
      collapse of the pharynx during sleep, has been increasingly recognized as a
      health issue of growing importance over the last decade. Recently emerging
      evidence suggests that there is a causal link between OSAS and hypertension, and
      hypertension represents an independent risk factor in OSAS patients. However, the
      pathophysiological basis for patients with OSAS having an increased risk for
      hypertension remains to be elucidated. The main acute physiological outcomes of
      OSAS are intermittent hypoxia, intrapleural pressure changes, and arousal from
      sleep, which might induce endothelial dysfunction, sympathetic activation, renin
      angiotensin-aldosterone system activation, lipid metabolism dysfunction, and
      increased oxidative stress. This brief review focuses on the current
      understanding of the complex association between OSAS and hypertension.

PMID- 23009228
TI  - Secluded and restrained patients' perceptions of their treatment.
AB  - Though some empirical and anecdotal accounts can be located in the extant
      literature, it remains the case that little is known about how
      secluded/restrained (S/R) patients perceive their overall treatment. The purpose
      of this study was to explore patients' perceptions of their hospital treatment
      measured after S/R. The data were collected with a Secluded and Restrained
      Patients' Perceptions of their Treatment (S/R-PPT) questionnaire from S/R
      patients aged 18-65 years. Ninety completed questionnaires were analysed.
      Patients perceived that they received enough attention from staff, and they were
      able to voice their opinions, but their opinions were not taken into account.
      Patients denied the necessity and beneficence of S/R. Women and older patients
      were more critical than men and younger patients regarding the use of
      restrictions. There were also statistically-significant differences in responses
      among patients at different hospitals. It is concluded that patients' opinions
      need more attention in treatment decisions. To achieve this, psychiatric
      treatment needs genuine dialogue between patients and staff, and individual care
      should have alternatives and no routine decisions. Therefore, the treatment
      culture must improve towards involving patients in treatment planning, and giving
      them a say when S/R is considered.

PMID- 23009229
TI  - Achieving quality and containing cost through oncology pharmacy management.

PMID- 23009227
TI  - The effects of varying acidity on Helicobacter pylori growth and the bactericidal
      efficacy of ampicillin.
AB  - BACKGROUND: Penicillins inhibit cell wall synthesis; therefore, Helicobacter
      pylori must be dividing for this class of antibiotics to be effective in
      eradication therapy. Identifying growth responses to varying medium pH may allow
      design of more effective treatment regimens. AIM: To determine the effects of
      acidity on bacterial growth and the bactericidal efficacy of ampicillin. METHODS:
      H. pylori were incubated in dialysis chambers suspended in 1.5-L of media at
      various pHs with 5 mM urea, with or without ampicillin, for 4, 8 or 16 h, thus
      mimicking unbuffered gastric juice. Changes in gene expression, viability and
      survival were determined. RESULTS: At pH 3.0, but not at pH 4.5 or 7.4, there was
      decreased expression of ~400 genes, including many cell envelope biosynthesis,
      cell division and penicillin-binding protein genes. Ampicillin was bactericidal
      at pH 4.5 and 7.4, but not at pH 3.0. CONCLUSIONS: Ampicillin is bactericidal at
      pH 4.5 and 7.4, but not at pH 3.0, due to decreased expression of cell envelope
      and division genes with loss of cell division at pH 3.0. Therefore, at pH 3.0,
      the likely pH at the gastric surface, the bacteria are nondividing and persist
      with ampicillin treatment. A more effective inhibitor of acid secretion that
      maintains gastric pH near neutrality for 24 h/day should enhance the efficacy of
      amoxicillin, improving triple therapy and likely even allowing dual amoxicillin
      based therapy for H. pylori eradication.

PMID- 23009230
TI  - Treatment and cost implications of pertuzumab.

PMID- 23009231
TI  - Rationalizing treatment and coverage decisions with predictive biomarkers.

PMID- 23009232
TI  - Implementation of cancer clinical care pathways.

PMID- 23009233
TI  - Trends in the 2012 Eisai Oncology Digest: counseling and communication of cancer
      treatment.

PMID- 23009234
TI  - The keys to obtaining best value in non-small cell lung cancer.

PMID- 23009238
TI  - How can we get better value in end-of-life care?

PMID- 23009239
TI  - Down the road for breast cancer.

PMID- 23009240
TI  - How payers and oncologists really feel about oncology pathways.

PMID- 23009241
TI  - Partnering with a payer to develop a value-based medical home pilot: a West Coast
      practice's experience.

PMID- 23009242
TI  - Oncology patient-centered medical home.

PMID- 23009243
TI  - Medical drug benefit management in the pathway era.

PMID- 23009244
TI  - Scale-up of home-based management of malaria based on rapid diagnostic tests and
      artemisinin-based combination therapy in a resource-poor country: results in
      Senegal.
AB  - BACKGROUND: Effective case management of malaria requires prompt diagnosis and
      treatment within 24 hours. Home-based management of malaria (HMM) improves access
      to treatment for populations with limited access to health facilities. In
      Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated
      use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP).
      Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861
      villages in 2010. This paper reports the results of the scale-up in the targeted
      communities and the impact of the strategy on malaria in the formal health
      sector. METHODS: Data reported by the HCPs were used to assess their performance
      in 2009 and 2010, while routine malaria morbidity and mortality data were used to
      assess the impact of the HMM programme. Two high transmission regions where HMM
      was not implemented until 2010 were used as a comparison. RESULTS AND DISCUSSION:
      From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93%
      (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a
      positive RDT, 97% (4126) of whom were reported treated and cured. Home care
      providers referred 6871 patients to health posts for management: 6486 with a
      negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases.
      There were no deaths among these patients. In 2009 compared to 2008, incidence of
      suspected and confirmed malaria cases, all hospitalizations and malaria-related
      hospitalizations decreased in both intervention and comparison regions. Incidence
      of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the
      intervention regions, while the decrease in comparison regions was smaller and
      not statistically significant. CONCLUSION: Home-based management of malaria
      including diagnosis with RDT and treatment based on test results is a promising
      strategy to improve the access of remote populations to prompt and effective
      management of uncomplicated malaria and to decrease mortality due to malaria.
      When scaled-up to serve remote village communities in the regions of Senegal with
      the highest malaria prevalence, home care providers demonstrated excellent
      adherence to guidelines, potentially contributing to a decrease in hospital
      deaths attributed to malaria.

PMID- 23009245
TI  - Orally active metabotropic glutamate subtype 2 receptor positive allosteric
      modulators: structure-activity relationships and assessment in a rat model of
      nicotine dependence.
AB  - Compounds that modulate metabotropic glutamate subtype 2 (mGlu(2)) receptors have
      the potential to treat several disorders of the central nervous system (CNS)
      including drug dependence. Herein we describe the synthesis and structure
      activity relationship (SAR) studies around a series of mGlu(2) receptor positive
      allosteric modulators (PAMs). The effects of N-substitution (R(1)) and
      substitutions on the aryl ring (R(2)) were identified as key areas for SAR
      exploration (Figure 3). Investigation of the effects of varying substituents in
      both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with
      improved in vitro potency and/or efficacy. In addition, several analogues
      exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was
      shown to dose-dependently decrease nicotine self-administration in rats following
      oral administration. Our data, showing for the first time efficacy of an mGlu(2)
      receptor PAM in this in vivo model, suggest potential utility for the treatment
      of nicotine dependence in humans.

PMID- 23009246
TI  - No red cell alloimmunization or change of clinical outcome after using fresh
      frozen cancellous allograft bone for acetabular reconstruction in revision hip
      arthroplasty: a follow up study.
AB  - BACKGROUND: Possible immunization to blood group or other antigens and subsequent
      inhibition of remodeling or incorporation after use of untreated human bone
      allograft was described previously. This study presents the immunological,
      clinical and radiological results of 30 patients with acetabular revisions using
      fresh frozen non-irradiated bone allograft. METHODS: AB0-incompatible (donor
      recipient) bone transplantation was performed in 22 cases, Rh(D) incompatible
      transplantation in 6 cases. The mean follow up of 23 months included measuring
      Harris hip score and radiological examination with evaluation of remodeling of
      the bone graft, implant migration and heterotopic ossification. In addition, all
      patients were screened for alloimmunization to Rh blood group antigens. RESULTS:
      Compared to the whole study group, there were no differences in clinical or
      radiological measurements for the groups with AB0- or Rh(D)-incompatible bone
      transplantation. The mean Harris Hip Score was 80.6. X-rays confirmed total
      remodeling of all allografts with no acetabular loosening. At follow up, blood
      tests revealed no alloimmunization to Rh blood group donor antigens. CONCLUSIONS:
      The use of fresh frozen non-irradiated bone allograft in acetabular revision is a
      reliable supplement to reconstruction. The risk of alloimmunization to donor
      blood group antigens after AB0- or Rh-incompatible allograft transplantation with
      a negative long-term influence on bone-remodeling or the clinical outcome is
      negligible.

PMID- 23009247
TI  - A prospective, multicenter, observational study of complicated skin and soft
      tissue infections in hospitalized patients: clinical characteristics, medical
      treatment, and outcomes.
AB  - BACKGROUND: Complicated skin and soft tissue infections (cSSTIs) occur
      frequently, but limited data do not allow any consensus on an optimal treatment
      strategy. We designed this prospective, multicenter, observational study to to
      explore the current epidemiology, treatment, and resulting clinical outcomes of
      cSSTIs to help develop strategies to potentially improve outcomes. METHODS: From
      June 2008 to December 2009 we enrolled a pre-specified number of adults treated
      in 56 U.S. hospitals with intravenous antibiotic(s) for any of the following
      cSSTIs: diabetic foot infection (DFI); surgical site infection (SSI); deep soft
      tissue abscess (DSTA); or, cellulitis. Investigators treated all patients per
      their usual practice during the study and collected data on a standardized form.
      RESULTS: We enrolled 1,033 patients (DFI 27%; SSI 32%; DSTA 14%; cellulitis 27%;
      mean age 54 years; 54% male), of which 74% had healthcare-associated risk
      factors. At presentation, 89% of patients received initial empiric therapy with
      intravenous antibiotics; ~20% of these patients had this empiric regimen changed
      or discontinued based on culture and sensitivity results. Vancomycin was the most
      frequently used initial intravenous antibiotic, ordered in 61% of cases. During
      their stay 44% of patients underwent a surgical procedure related to the study
      infection, usually incision and drainage or debridement. The mean length of stay
      was 7.1 days, ranging from 5.8 (DSTA) to 8.1 (SSI). CONCLUSION: Our findings from
      this large prospective observational study that characterized patients with
      cSSTIs from diverse US inpatient populations provide useful information on the
      current epidemiology, clinical management practices and outcomes of this common
      infection.

PMID- 23009248
TI  - The impact of dis-/reconnection of laser microgrooved and machined implant
      abutments on soft- and hard-tissue healing.
AB  - OBJECTIVES: To (i) investigate the influence of different extensions of a laser
      microgrooved abutment zone on connective tissue attachment and (ii) assess the
      impact of a repeated abutment dis-/reconnection on soft- and hard-tissue healing.
      MATERIALS AND METHODS: Titanium implants were inserted epicrestally in the lower
      jaws of six dogs. Healing abutments with either partially (LP) or completely (LC)
      laser microgrooved margins or machined surface margins (M) were randomly
      allocated either to a single (1*)/repeated (2*) dis-/reconnection at 4 and 6
      weeks (test), respectively, or left undisturbed (control). At 6 and 8 weeks,
      histomorphometrical (e.g. most coronal level of bone in contact with the implant
      [CBI], subepithelial connective tissue attachment [STC]) and immunohistochemical
      (Collagen Type-I [CI]) parameters were assessed. RESULTS: At control sites, LP/LC
      groups revealed lower mean CBL (8 weeks, 0.95 +/- 0.51 vs. 0.54 +/- 0.63 vs. 1.66
      +/- 1.26 mm), higher mean STC (8 weeks, 82.58 +/- 24.32% vs. 96.37 +/- 5.12% vs.
      54.17 +/- 8.09%), but comparable CI antigen reactivity. A repeated abutment
      manipulation was associated with increased mean CBL (8 weeks, 1.53 +/- 1.09 vs.
      0.94 +/- 0.17 vs. 1.06 +/- 0.34 mm), decreased STC (8 weeks, 57.34 +/- 43.06% vs.
      13.26 +/- 19.04% vs. 37.76 +/- 37.08%) and CI values. CONCLUSIONS: It was
      concluded that (i) LC>LP abutments enhanced subepithelial connective tissue
      attachment and preserved crestal bone levels, (ii) repeated abutment dis
      /reconnection during the initial healing phase (4-6 weeks) may be associated with
      increased soft- and hard-tissue changes and (iii) LP and LC should be considered
      using a one abutment, one time approach.

PMID- 23009250
TI  - PBL Scenario Bank.

PMID- 23009249
TI  - The efficacy of i-SCAN for detecting reflux esophagitis: a prospective randomized
      controlled trial.
AB  - New imaging technologies have been applied in endoscopy to improve the detection
      and differentiation of subtle mucosal changes using a digital contrast method.
      Among them, i-SCAN technology is the most recently developed image-enhancing
      technology. We investigated whether i-SCAN could improve the detection rate of
      reflux esophagitis. Interobserver agreement between endoscopists was compared
      with conventional white light (WL) endoscopic examination. We performed a
      prospective randomized controlled trial. A consecutive series of 514 subjects
      that underwent an esophagogastroduodenoscopy for health inspection were enrolled
      and randomized into the i-SCAN group (n = 246) and WL group (n = 268). An
      esophagogastroduodenoscopy with video recording was used for detecting reflux
      esophagitis, and reflux esophagitis were categorized by the modified Los Angeles
      (LA) classification. The total number of reflux esophagitis identified by WL and
      i-SCAN was 58 (21.7%) and 74 (30.1%), respectively. The diagnostic yield of
      reflux esophagitis was significantly higher (P = 0.034) in the i-SCAN group
      (30.1%) as compared to the WL group (21.6%). Using the modified LA
      classification, the detection rate of minimal changes was significantly higher (P
      = 0.017) in the i-SCAN group (11.8%) as compared to the WL group (5.6%), but the
      detection rates of LA-A and LA-B were not significantly different between the two
      groups (P = 0.897 and P = 0.311, respectively). After comparison of the
      interobserver agreement using randomly selected video clips, the i-SCAN group
      showed better agreement than the WL group (Kappa value, 0.793 vs. 0.473).
      Compared to WL endoscopy, applying i-SCAN in daily practice can improve the
      diagnostic yield of reflux esophagitis by detecting more minimal changes in the
      squamo-columnar junction of the esophagus and can improve the interobserver
      agreement of the modified Los Angeles classification.

PMID- 23009251
TI  - Unexpected findings from an interdisciplinary case conference.

PMID- 23009252
TI  - Who teaches the evidence-based medicine teacher?

PMID- 23009253
TI  - Acceptability of the extended matching question format as formative assessment in
      online continuing professional development.

PMID- 23009254
TI  - Comparison of three problem-based learning conditions (real patients, digital and
      paper) with lecture-based learning in a dermatology course: a prospective
      randomized study from China.
AB  - BACKGROUND: The precise effect and the quality of different cases used in
      dermatology problem-based learning (PBL) curricula are yet unclear. AIM: To
      prospectively compare the impact of real patients, digital, paper PBL (PPBL) and
      traditional lecture-based learning (LBL) on academic results and student
      perceptions. METHODS: A total of 120 students were randomly allocated into either
      real-patients PBL (RPBL) group studied via real-patient cases, digital PBL (DPBL)
      group studied via digital-form cases, PPBL group studied via paper-form cases, or
      conventional group who received didactic lectures. Academic results were assessed
      through review of written examination, objective structured clinical examination
      and student performance scores. A five-point Likert scale questionnaire was used
      to evaluate student perceptions. RESULTS: Compared to those receiving lectures
      only, all PBL participants had better results for written examination, clinical
      examination and overall performance. Students in RPBL group exhibited better
      overall performance than those in the other two PBL groups. Real-patient cases
      were more effective in helping develop students' self-directed learning skills,
      improving their confidence in future patient encounters and encouraging them to
      learn more about the discussed condition, compared to digital and paper cases.
      CONCLUSION: Both real patient and digital triggers are helpful in improving
      students' clinical problem-handling skills. However, real patients provide
      greater benefits to students.

PMID- 23009255
TI  - How to stay mentally healthy during medical education. Stress coping and
      relaxation behaviour of female and male students.

PMID- 23009256
TI  - Selection of medical students in Taiwan.

PMID- 23009257
TI  - Development of emotional intelligence in a team-based learning internal medicine
      clerkship.
AB  - BACKGROUND: Although increasing number of articles have been published on team
      based learning (TBL), none has explored team emotional intelligence. AIM: We
      extend the literature by examining changes in team emotional intelligence during
      a third year clerkship where TBL is a primary instructional strategy. We
      hypothesized that team emotional intelligence will change in a positive direction
      (i.e., increase) during the clerkship. METHOD: With IRB approval, during the 2009
      2010 academic year third-year students in their internal medicine clerkship (N =
      105, 100% response rate) completed the Workgroup Emotional Intelligence Profile -
      Short Version (WEIP-S) at the beginning and at the end of their 12-week
      clerkship. TBL is an instructional strategy utilized during the internal medicine
      clerkship. RESULTS: Paired t-tests showed that team emotional intelligence
      increased significantly pre to post clerkship for three of the four areas:
      awareness of own emotions (p = 0.018), recognizing emotions in others (p =
      0.031), and ability to manage other's emotions (p = 0.013). There was no change
      for ability to control own emotions (p = 0.570). CONCLUSION: In an internal
      medicine clerkship, where TBL is utilized as an instructional strategy, team
      emotional intelligence increases. This supports TBL as an adjunctive tool to
      traditional medical education pedagogy.

PMID- 23009258
TI  - Photosystem I in Langmuir-Blodgett and Langmuir-Schaefer monolayers.
AB  - Photosystem I (PSI) is a membrane protein complex that generates photoinduced
      electrons and transfers them across the thylakoid membrane during photosynthesis.
      The PSI complex, separated from spinach leaves, was spread onto the air-water
      interface as a monolayer and transferred onto a gold electrode surface that was
      precoated with a self-assembled monolayer (SAM). The electrochemical properties
      of the transferred PSI monolayer, including cyclic voltammetry and photoinduced
      chronoamperometry, were measured. The results showed that PSI retained its
      bioactivity after the manipulation. Its capability of converting photoenergy into
      electrical potential was demonstrated by its reducing an electron acceptor,
      dichloroindophenol (DCIP), and by oxidizing an electron donor, sodium ascorbate
      (ASC). We have shown that the protein has two possible orientations at the water
      interface. The orientation distribution was determined by comparing the
      controlled reductive and oxidative photocurrents generated from Langmuir-Blodgett
      and Langmuir-Schaefer monolayers.

PMID- 23009259
TI  - Secondhand smoke in combination with ambient air pollution exposure is associated
      with increasedx CpG methylation and decreased expression of IFN-gamma in T
      effector cells and Foxp3 in T regulatory cells in children.
AB  - BACKGROUND: Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have
      been associated with increased prevalence and severity of asthma and DNA
      modifications of immune cells. In the current study, we examined the association
      between SHS and AAP with DNA methylation and expression of interferon-gamma (IFN
      gamma) and forkhead box protein 3 (Foxp3) in T cell populations. METHODS:
      Subjects 7-18 years old were recruited from Fresno (high AAP; n = 62) and
      Stanford, CA (low AAP; n = 40) and divided into SHS-exposed (Fresno: n = 31,
      Stanford: n = 6) and non-SHS-exposed (nSHS; Fresno: n = 31, Stanford: n = 34)
      groups. T cells purified from peripheral blood were assessed for levels of DNA
      methylation and expression of IFN-gamma (in effector T cells) or Foxp3 (in
      regulatory T cells). RESULTS: Analysis showed a significant increase in mean %
      CpG methylation of IFN-gamma and Foxp3 associated with SHS exposure (IFN-gamma:
      FSHS 62.10%, FnSHS 41.29%, p < 0.05; SSHS 46.67%, SnSHS 24.85%, p < 0.05; Foxp3:
      FSHS 74.60%, FnSHS 54.44%, p < 0.05; SSHS 62.40%, SnSHS 18.41%, p < 0.05) and a
      significant decrease in mean transcription levels of both genes (IFN-gamma: FSHS
      0.75, FnSHS 1.52, p < 0.05; SHS 2.25, nSHS 3.53, p < 0.05; Foxp3: FSHS 0.75,
      FnSHS 3.29, p < 0.05; SSHS 4.8, SnSHS 7.2, p < 0.05). AAP was also associated
      with hypermethylation (IFN-gamma: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p <
      0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05) and decreased
      transcription of both genes (IFN-gamma: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS,
      p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05). Average
      methylation between AAP- and SHS-only exposures was not significantly different
      (IFN-gamma: p = 0.15; Foxp3: p = 0.27), nor was Foxp3 expression (p = 0.08); IFN
      gamma expression was significantly decreased in AAP-only subjects (p < 0.05).
      CONCLUSIONS: Exposures to SHS and AAP are associated with significant
      hypermethylation and decreased expression of IFN-gamma in Teffs and Foxp3 in
      Tregs. Relative contributions of each exposure to DNA modification and asthma
      pathogenesis warrant further investigation.

PMID- 23009260
TI  - Pleural function and lymphatics.
AB  - The pleural space plays an important role in respiratory function as the negative
      intrapleural pressure regimen ensures lung expansion and in the mean time
      maintains the tight mechanical coupling between the lung and the chest wall. The
      efficiency of the lung-chest wall coupling depends upon pleural liquid volume,
      which in turn reflects the balance between the filtration of fluid into and its
      egress out of the cavity. While filtration occurs through a single mechanism
      passively driving fluid from the interstitium of the parietal pleura into the
      cavity, several mechanisms may co-operate to remove pleural fluid. Among these,
      the pleural lymphatic system emerges as the most important one in quantitative
      terms and the only one able to cope with variable pleural fluid volume and
      drainage requirements. In this review, we present a detailed account of the
      actual knowledge on: (a) the complex morphology of the pleural lymphatic system,
      (b) the mechanism supporting pleural lymph formation and propulsion, (c) the
      dependence of pleural lymphatic function upon local tissue mechanics and (d) the
      effect of lymphatic inefficiency in the development of clinically severe pleural
      and, more in general, respiratory pathologies.

PMID- 23009261
TI  - Traumatic intercostal arterial bleeding controlled with a novel surgical
      technique: a case report.
AB  - INTRODUCTION: A blunt thoracic trauma may cause arterial bleeding requiring
      operative treatment or endovascular embolization or endovascular aortic stenting.
      A novel damage control technique to stop such bleeding is presented. CASE
      PRESENTATION: We present the case of an 82-year-old Caucasian man who experienced
      rib fractures I-VII on the left side and bleeding from damaged intercostal
      arteries after a blunt thoracic trauma. Emergency thoracotomy was performed.
      CONCLUSIONS: Effective hemostasis was achieved by using a rolled surgical swab
      and inserting it against the chest wall next to the aorta with sutures pulled
      through the intercostal muscles and then sutured to the back side of the patient.
      The patient died four days after the surgery due to a head injury sustained in
      the car crash.

PMID- 23009262
TI  - The association between alcohol and tobacco use among elementary and high school
      students in Crete, Greece.
AB  - BACKGROUND: Tobacco and alcohol use during adolescence have potential long term
      health consequences and a possibility of future addiction. METHODS: This cross
      sectional study took place in 2007 among a convenience sample of 981 adolescents
      from public elementary and high schools in Eastern Crete, Greece. Following
      parental consent, an anonymous structured questionnaire including information on
      personal and family use of alcohol and tobacco was distributed. RESULTS: Among
      the entire study population, cigarette experimentation was found to be associated
      with current alcohol use, with an Adjusted Odds Ratio (aOR) of 38.8; (95%C.I:
      5.33-58.2) and with having a smoker in the immediate family (aOR 10.3; 95%C.I:
      3.14-34.0). Among the subset of elementary school children, cigarette smoking was
      strongly associated with current alcohol use aOR 9.7; (95%C.I: 2.12-44.3), while
      the association between smoking experimentation and sibling and parental alcohol
      use was statistically significant within the entire population (however not among
      elementary students) with an aOR of 2.76 (95%C.I: 1.24-6.15) and aOR 3.66,
      (95%C.I: 1.97-6.81) respectively. The elementary child's gender was not found to
      be associated with cigarette experimentation among this study population.
      CONCLUSIONS: Strong associations were found between alcohol use and tobacco
      experimentation. The potential parental influence on consequent adolescent
      tobacco and alcohol use was also noted. Potential community based interventions,
      if launched in Greece, should take the role of the Greek family into account.

PMID- 23009263
TI  - Ophthalmological findings in a closed herd of Lipizzaners.
AB  - REASONS FOR PERFORMING THE STUDY: There are no studies on the ophthalmic health
      status in the Lipizzaner breed. OBJECTIVE: To perform an ophthalmological survey
      in a closed herd in 3 housing systems. MATERIALS: All horses at the Federal Stud
      Piber, Heldenberg and the Spanish Riding School Vienna were subjected to
      ophthalmological examination. Findings were documented and correlated with
      factors such as age, gender, location and housing situation. The interrelation of
      abnormalities of different regions was determined by calculating accuracy.
      Pedigree analysis of horses affected by cataract was performed. RESULTS: A total
      of 267 horses met the inclusion criteria of this study. Of these, 172 horses were
      stabled in Piber, 72 in Vienna and 23 in Heldenberg. Ophthalmological examination
      revealed 203 cases with ocular findings, predominantly involving the conjunctiva
      (44.6%), cornea (21.7%) and fundus (37.5%). In 24 (8.9%) horses a diagnosis of
      cataract was made. There was no interrelation between different eye diseases.
      Horses stabled at Piber were significantly more affected by conjunctival and
      fundic abnormalities. Fewer abnormalities were found in horses stabled in open
      boxes. Access to free stalls resulted in more cases of conjunctivitis. Pedigree
      analysis showed no evidence of inbreeding as a cause of cataract formation.
      CONCLUSION AND POTENTIAL RELEVANCE: Acquired corneal abnormalities were over
      represented in this study. This survey may serve as a basis for further research
      on the pathogenesis of ophthalmic diseases in Lipizzaners.

PMID- 23009264
TI  - The antiapoptotic activity of Heligmosomoides polygyrus antigen fractions.
AB  - Our study identified Heligmosomoides polygyrus antigen factors with potential
      activity for regulation of T-cell proliferation and surviving of CD4(+) CD25(-) ,
      CD4(+) CD25(hi) and CD3(+) CD8(+) cell populations. The antiapoptotic activity of
      antigenic fractions separated by HPLC was evaluated in vitro after exposure of
      cells to DEX and rTNF-alpha. Different populations of cells responded to antigen
      fractions in distinct pattern; the most sensitive population of cells to H.
      polygyrus products were CD4(+) CD25(hi) after exposure to DEX and CD3(+) CD8(+) T
      cells after exposure to rTNF-alpha. H. polygyrus antigens may influence survival
      of CD8(+) T cells by regulation of c-FLIP rather than Bcl-2, which affects
      survival of CD4(+) CD25(hi) Treg cells and CD4(+) T cells. Activation of NF
      kappaB subunits, for example, p50 and p65 was essential for resistance of cells
      to apoptosis, and antigenic fractions F9 and F17 exerted different effect to F13.
      The most active fraction in inhibition of apoptosis was F9, which includes Hsp
      60, calumenin, ferritin, galectin and thrombospondin. This study may provide new
      clues for recognition of factors that regulate the immune response during
      infection and which engage the TNF-alpha receptor-mediated and the mitochondria
      mediated death pathway.

PMID- 23009265
TI  - Comparison of the Huggins band for six ozone isotopologues: vibrational levels
      and absorption cross section.
AB  - By use of the 3(1)A' ab initio potential energy surface (PES) of ozone and the
      multi-configuration time-dependent Hartree program for wavepacket propagation, we
      have determined numerous eigenstates of this state for six ozone isotopologues.
      These bound vibrational levels are the upper levels of the Huggins band, which
      covers the range from 27,000 to ~33,000 cm(-1). This study extends our previous
      work on the Hartley band, which was limited to the range ~32,000-50,000 cm(-1).
      Four isotopologues, (16)O(3), (16)O(17)O(16)O, (16)O(18)O(16)O, and (18)O(3)
      (noted hereafter 666, 676, 686, and 888), are symmetric, and two are asymmetric,
      (17)O(16)O(2) and (18)O(16)O(2) (noted hereafter 667 and 668). The PES of the
      3(1)A' state has two equivalent minima of C(s) symmetry located at ~27,000 cm(-1)
      above the X(1)A(1) ground state. The equilibrium geometry of these two minima is
      r(e(1)) = 2.28 a(0), r(e(2)) = 3.2 a(0), and theta(e) = 107 degrees . The
      dissociation limit of this PES, which correlates to the O((1)D) + O(2) ((1)Delta)
      "singlet" channel, is about 4300 cm(-1) above the two minima. For the (16)O(3)
      isotopologue, the 120 lowest bound eigenstates have been calculated and partially
      assigned up to 800 cm(-1) below the dissociation limit. The 60 lower eigenstates
      are easily assignable in term of three normal modes, the "long" bond (nu(1)), the
      bending (nu(2)), and the "short" bond (nu(3)). A new family of wave functions,
      aligned along the dissociation channels, appears at 3782 cm(-1) above the 3(1)A'
      (0,0,0) level. The 3(1)A' vibrational levels and the corresponding intensity
      factors from the (000), (010), (100), and (001) levels of the X(1)A(1) ground
      state have been calculated for the six isotopologues. The Huggins absorption
      cross sections of the six isotopologues have been calculated from the 3(1)A'
      vibrational energy levels and the corresponding intensity factors. The rotational
      envelope of each vibronic band has been empirically described by an ad hoc
      function. The ratio of the Huggins cross section of each ozone isotopologue with
      one of (16)O(3) provides the fractionation factor of each ozone isotopologue as a
      function of the photon energy. These various fractionation factors will allow
      predicting enrichments due to photolysis by various light sources like the
      actinic flux.

PMID- 23009266
TI  - PEG conjugation of a near-infrared fluorescent probe for noninvasive dual imaging
      of lung deposition and gene expression by pulmonary gene delivery.
AB  - Dual imaging of lung deposition and gene expression following the pulmonary
      delivery of a gene formulation is useful for a precise analysis of gene
      transfection efficiency in vivo. As a novel probe for evaluating lung deposition,
      in this study, a poly(ethylene glycol)-conjugated near-infrared fluorescent probe
      (PEG-NIRF) was newly synthesized, and compared with indocyanine green (ICG), for
      application to pDNA/polyethyleneimine (PEI) complex. PEG-NIRF had superior
      characteristics including a larger Stokes shift (absorption maximum, 662 nm;
      emission maximum, 772 nm) and relatively equivalent fluorescence intensity
      compared with ICG. ICG affected the physicochemical properties of pDNA/PEI
      complex with a loss of fluorescence intensity, while PEG-NIRF did not.
      Experiments in mice demonstrated that PEG-NIRF showed greater lung localization
      than ICG following pulmonary co-delivery with pDNA/PEI complex, indicating the
      possibility of accurately evaluating lung deposition. Moreover, it was clarified
      that the evaluation of lung deposition by PEG-NIRF even at 60 min could be
      significantly correlated with gene expression in each mouse following pulmonary
      co-delivery with pDNA/PEI complex. These results suggest that PEG-NIRF is widely
      applicable to the dual imaging of the lung deposition and gene expression of
      inhaled gene formulations.

PMID- 23009267
TI  - Editorial: plagiarism: words and ideas.

PMID- 23009268
TI  - Risk assessment as a paradox: when actions of an IRB become incompatible with
      ethical principles.
AB  - As anecdotal evidence mounts up of Institutional Review Boards becoming an
      impediment to research, I share a personal experience in this article to argue
      how the conduct of an Institutional Review Board was incompatible with a number
      of ethical principles such as Respect for Persons, Deception, Informed Consent,
      and Justice. I conclude by promoting Evidence-Based Ethical Problem Solving to
      facilitate and enhance risk assessments through empirical evidence.

PMID- 23009269
TI  - Are research papers reporting results from nutrigenetics clinical research a
      potential source of biohype?
AB  - Nutrigenetics is a promising field, but the achievability of expected benefits is
      challenged by the methodological limitations that are associated with clinical
      research in that field. The mere existence of these limitations suggests that
      promises about potential outcomes may be premature. Thus, benefits claimed in
      scientific journal articles in which these limitations are not acknowledged might
      stimulate biohype. This article aims to examine whether nutrigenetics clinical
      research articles are a potential source of biohype. Of the 173 articles
      identified, 16 contained claims in which clinical applications were extrapolated
      from study results. The methodological limitations being incompletely
      acknowledged, these articles could potentially be a source of biohype.

PMID- 23009270
TI  - Preparing whistleblowers for reporting research misconduct.
AB  - Making an allegation of research misconduct can be stressful for a whistleblower.
      The Research Integrity Officer (RIO) can play an important role in helping reduce
      the stress by thoroughly discussing what whistleblowers can expect if they make
      an allegation. Through interviews with 77 RIOs who had recently handled a
      research misconduct case, we found that RIOs who addressed more topics as well as
      specific aspects of the topics were more likely to have used some type of memory
      aide in their initial contact with whistleblowers, talked with ORI staff or other
      RIOs about "hypothetical" research misconduct cases, or attended a RIO boot camp
      training. We believe that RIOs who more fully inform whistleblowers are providing
      timely preparation and building whistleblowers' confidence so they can make a
      more informed decision about reporting and experience less stress.

PMID- 23009271
TI  - An alternative approach for locating a mammographic lesion by ultrasound using a
      simple x,y coordinate system.
AB  - We present an accurate and reliable method for localizing a mammographic lesion
      by ultrasound using a simple coordinate system. It does not require special grid
      equipment or additional personnel. We use our system, step-by-step, on a sample
      patient and include appropriate image documentation. The nipple is the point of
      reference or "origin". The lesion is located on ultrasound using its x and y
      coordinates, which are the two distances from the nipple in the horizontal and
      vertical axes, measured with an ordinary ruler or caliper tool. The true distance
      from the nipple can also easily be measured and reported. Our method is
      reproducible and shortens ultrasound exam times to less than 10 minutes.

PMID- 23009272
TI  - Development of a live tissue microtome: reflections of an amateur machinist.
AB  - Live circular tissue slices of nearly identical diameter and thickness can be
      generated from most tissues by the use of two instruments; a coring tool to cut
      cylindrical tissue cores which are subsequently sliced by a microtome into thin
      circular sections 5-8 mm in diameter and 50-300 microns thick. The sections are
      of very similar geometry permitting direct comparisons without normalization.
      Both instruments operate submerged in a cold isotonic medium that caries the cut
      slices outside the microtome. The slices are cut by a rapidly oscillating
      disposable Gillette blade mounted at an angle of 20 degrees to the vertical main
      axis of the tissue core. The latter is advanced against the oscillating blade by
      a weighted plunger pushing it against a screw adjustable limit plate that defines
      the desired slice thickness. Both instruments can be sterilized and slices can be
      obtained at a rate of approximately one every ten seconds.

PMID- 23009273
TI  - The changing pattern of renal amyloidosis in Indian subcontinent: two decades of
      experience from a single center.
AB  - BACKGROUND: Renal amyloidosis is a major cause of morbidity and mortality among
      the patients of systemic amyloidosis. The causes of amyloidosis vary from country
      to country and from time to time at individual center. AIM: This study
      investigates the changes in epidemiological and clinical profile of renal
      amyloidosis in recent years. METHOD: Cases of biopsy-proven renal amyloidosis
      from January 1992 to December 2010 were studied retrospectively. They were
      divided into two groups: 1990s (between 1992 and 2002) and 2000s (between 2003
      and 2010). The clinical characteristics of patients were studied and compared
      between the groups. RESULT: A total of 2498 (974 in 1990s and 1524 in 2000s)
      renal biopsies was done during the 19-year period. The incidence of amyloidosis
      in 1990s and 2000s was 1.74% (n = 17) and 1.9% (n = 29), respectively (p > 0.05).
      We noted that the incidence of renal amyloidosis increased significantly (p <
      0.05) among the females in 2000s. The mean age of patients in 2000s and 1990s was
      38 +/- 17.9 and 39.2 +/- 19 years, respectively (p = 0.83). Renal insufficiency
      in patients with renal amyloidosis significantly increased (p < 0.05) in 2000s (n
      = 14; 48.2%) in comparison to 1990s (n = 2; 12.8%). Subnephrotic proteinuria was
      observed in 12.8% (n = 2) and 48.82% (n = 14) of patients in 1990s and 2000s,
      respectively (p < 0.05). Infection (n = 10; 58.8%) was the most common cause of
      secondary amyloidosis during the 1990s, whereas chronic inflammation (n = 14;
      48.2%) was the most common cause in 2000s. In 1990s, the incidence of ankylosing
      spondylitis (AS) and rheumatoid arthritis (RA) was 11.7% (n = 2) and 5.8% (n =
      1), respectively, but in 2000s, their respective incidence was 17.2% (n = 5)
      each. Multiple myeloma (MM) was the most common cause of amyloid light chain
      protein (AL) amyloidosis in both the groups. We observed systemic lupus
      erythromatosus (SLE)-related renal amyloidosis in two cases and Hodgkin lymphoma
      associated amyloidosis in one case in 2000s. CONCLUSION: The overall incidence of
      renal amyloidosis showed little change from 1990s to 2000s. Chronic inflammatory
      diseases were the most common cause of renal amyloidosis in 2000s in contrast to
      infections in 1990s. Female gender was more affected in 2000s than in 1990s.
      Renal insufficiency and subnephrotic-range proteinuria were more frequent
      clinical manifestations of renal amyloidosis in recent years (2000s) in
      comparison to the earlier decade (1990s).

PMID- 23009274
TI  - The differing impact of induced astigmatic blur on crowded and uncrowded
      paediatric visual acuity chart results.
AB  - PURPOSE: Vision screening programs often rely on acuity measures to detect
      significant refractive error and clinicians use measures of acuity to monitor
      refractive treatment. This study investigated the effects of induced astigmatism
      on visual acuity (VA) using several paediatric acuity tests: the Keeler LogMAR
      crowded and single letter acuity tests, the single letter Sheridan Gardiner
      chart, and the crowded and single Kay picture tests. METHODS: Six fully-corrected
      emmetropic adults had induced astigmatic blur imposed at different axes of
      astigmatism (90 degrees , 180 degrees , 135 degrees , 45 degrees ). Astigmatic
      errors ranged from 0.75 to 3.50 DC. Monocular VA was measured with induced
      astigmatic blur for each acuity test. Participants and examiner were masked to
      the axis and power of the astigmatism. RESULTS: All participants demonstrated
      similar variability in performance across acuity charts (p = 0.54). For all
      charts, there was a linear reduction in VA with increasing amounts of induced
      astigmatism. The Keeler crowded LogMAR acuity test required the least amount of
      astigmatic blur to exceed a 0.2 LogMAR threshold (1.17 D, for 90 degrees  induced
      astigmatism), while the crowded and single Kay pictures required the largest
      magnitudes (2.09 and 2.85 D for 90 degrees  induced astigmatism respectively).
      The most variable acuities were recorded within and between participants with the
      Sheridan Gardiner chart. CONCLUSIONS: The present study demonstrated that none of
      the acuity charts under test are likely to detect uncorrected astigmatic
      refractive error unless the magnitude of astigmatism is large. Given the
      limitations of other paediatric acuity charts under test, it is important that
      practitioners use a crowded, LogMAR letter chart as soon as it is feasible.

PMID- 23009275
TI  - A clinical primer on restless legs syndrome: what we know, and what we don't
      know.
AB  - Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common
      sensorimotor disorder that may be idiopathic (primary) or secondary to a diverse
      group of conditions. The pathophysiology of primary RLS is only partly
      understood, but a strong association with brain iron deficiency possibly
      resulting in impaired dopaminergic function has been recognized. Genomic studies
      have established a genetic basis for primary RLS as well, and at least 42% of
      people with primary RLS possess a first-degree relative with the disorder.
      Secondary RLS is often associated with renal insufficiency, pregnancy, iron
      deficiency anemia, diabetic neuropathy, and Parkinson's disease. Approximately
      one-fourth of pregnant women experience RLS, with more intense symptoms
      experienced during the third trimester, and resolution of symptoms typically
      occurring within a few months after delivery, though RLS may resolve as early as
      2 weeks after delivery. Restless legs syndrome is associated with increased
      prevalence of mood disturbances, sleep disturbances, and an impaired quality of
      life. The diagnosis of RLS involves 4 essential criteria related to a compelling
      urge to move the legs with an accompanying unpleasant sensation in the legs that
      is worse in the evening and at rest and improved by movement. Treatment of RLS
      incorporates both pharmacologic and nonpharmacologic approaches. Dopamine
      agonists are the mainstay of RLS treatment, but other therapies, including
      gabapentin, benzodiazepines, and low-potency opioids, are also commonly employed.

PMID- 23009276
TI  - Reflective practice groups for nurses: a consultation liaison psychiatry nursing
      initiative: part 1--The model.
AB  - In the present study, we outline the evolution of a process-focused reflective
      practice group (RPG) model for nurses working in clinical settings. The groups
      were initiated at Redcliffe and Caboolture hospitals by the consultation liaison
      psychiatry nurse and author. An associated article provides an evaluation of
      these RPG. The literature review identifies the key themes and theories on which
      the model is based, and the article outlines the process and practicalities of
      facilitating RPG in critical care, midwifery, and oncology specialties over a 3
      year period. The model proposes that the effectiveness and sustainability of RPG
      arises from adequate preparation and engagement with prospective participants.
      Group rules, based on principles of confidentially, supportiveness, and
      diversity, were collaboratively developed for each group. Facilitation utilized a
      group-as-a-whole approach to manage process and stimulate reflection. While the
      purpose of RPG was a reflection on interpersonal aspects of nursing, contextual
      workplace issues were frequently raised in groups. Acknowledgement and
      containment of such issues were necessary to maintain clinical focus. The
      literature highlights facilitator credibility and style as crucial factors in the
      overall success of RPG, and it is proposed that reflective practice as a process
      focused model for groups succeeds when nurse facilitators are trained in group
      process and receive concurrent supervision.

PMID- 23009277
TI  - Outcomes of a classroom-based team training intervention for multi-professional
      hospital staff.

PMID- 23009278
TI  - Marine proteomics: a critical assessment of an emerging technology.
AB  - The application of proteomics to marine sciences has increased in recent years
      because the proteome represents the interface between genotypic and phenotypic
      variability and, thus, corresponds to the broadest possible biomarker for eco
      physiological responses and adaptations. Likewise, proteomics can provide
      important functional information regarding biosynthetic pathways, as well as
      insights into mechanism of action, of novel marine natural products. The goal of
      this review is to (1) explore the application of proteomics methodologies to
      marine systems, (2) assess the technical approaches that have been used, and (3)
      evaluate the pros and cons of this proteomic research, with the intent of
      providing a critical analysis of its future roles in marine sciences. To date,
      proteomics techniques have been utilized to investigate marine microbe, plant,
      invertebrate, and vertebrate physiology, developmental biology, seafood safety,
      susceptibility to disease, and responses to environmental change. However, marine
      proteomics studies often suffer from poor experimental design, sample
      processing/optimization difficulties, and data analysis/interpretation issues.
      Moreover, a major limitation is the lack of available annotated genomes and
      proteomes for most marine organisms, including several "model species". Even with
      these challenges in mind, there is no doubt that marine proteomics is a rapidly
      expanding and powerful integrative molecular research tool from which our
      knowledge of the marine environment, and the natural products from this resource,
      will be significantly expanded.

PMID- 23009280
TI  - Symptomatic knee disorders in floor layers and graphic designers. A cross
      sectional study.
AB  - BACKGROUND: Previous studies have described an increased risk of developing tibio
      femoral osteoarthritis (TF OA), meniscal tears and bursitis among those with a
      trade as floor layers. The purpose of this study was to analyse symptomatic knee
      disorders among floor layers that were highly exposed to kneeling work tasks
      compared to graphic designers without knee-demanding work tasks. METHODS: Data on
      the Knee injury and Osteoarthritis Outcome Score (KOOS) were collected by
      questionnaires. In total 134 floor layers and 120 graphic designers had a
      bilateral radiographic knee examination to detect TF OA and patella-femoral (PF)
      OA. A random sample of 92 floor layers and 49 graphic designers had Magnetic
      Resonance Imaging (MRI) of both knees to examine meniscal tears. Means of the
      subscales of KOOS were compared by analysis of variance. The risk ratio of
      symptomatic knee disorders defined as a combination of radiological detected knee
      OA or MRI-detected meniscal tears combined with a low KOOS score was estimated by
      logistic regression in floor layers with 95% confidence interval (CI) and
      adjusted for age, body mass index, traumas, and knee-straining sports activities.
      Symptomatic knee OA or meniscal tears were defined as a combination of low KOOS
      scores and radiographic or MRI pathology. RESULTS: Symptomatic TF and medial
      meniscal tears were found in floor layers compared to graphic designers with odds
      ratios 2.6 (95%CI 0.99-6.9) and 2.04 (95% CI 0.77-5.5), respectively. There were
      no differences in PF OA. Floor layers scored significantly lower on all KOOS
      subscales compared to graphic designers. Significantly lower scores on the KOOS
      subscales were also found for radiographic TF and PF OA regardless of trade but
      not for meniscal tears. CONCLUSIONS: The study showed an overall increased risk
      of developing symptomatic TF OA in a group of floor layers with a substantial
      amount of kneeling work positions. Prevention would be appropriate to reduce the
      proportion of kneeling postures e.g. by working with tools used from a standing
      working position.

PMID- 23009281
TI  - Preparation of gelatin hydrogels incorporating small interfering RNA for the
      controlled release.
AB  - The objective of this study is to design biodegradable hydrogels of gelatin for
      the controlled release of bioactive small interfering RNA (siRNA). Gelatin was
      cationized by chemically introducing ethylene diamine into the carboxyl groups in
      different conditions to obtain cationized gelatins (CGs). The CG was mixed with
      siRNA at various mixing ratios of amino groups of gelatin to the phosphate groups
      of siRNA in aqueous solution to form the siRNA-CGnano-complex. Gelatin together
      with the complex of siRNA and CG was chemically crosslinked to prepare the
      gelatin hydrogel incorporating the complex. The hydrogel incorporating the siRNA
      CG complex was hardly degraded in phosphate-buffered saline solution (PBS) at 37
      degrees C and did not release the siRNA complex after initial siRNA release. When
      placed in PBS containing collagenase, the hydrogel was enzymatically degraded to
      release the siRNA complex. In this release system, the siRNA was released as a
      result of hydrogel degradation. The siRNA released showed an activity to
      specifically suppress the expression of the corresponding gene. The hydrogel is
      promising to release siRNA and also elicit biological activity for a longer time.

PMID- 23009283
TI  - Interprosthetic humeral fracture revision using a tibial allograft total elbow
      prosthetic composite in a patient with hemophilia A : a case report.
AB  - INTRODUCTION: Interprosthetic fractures of the humerus are rare. Revisions of
      total elbow arthroplasty components in these cases are difficult. We report the
      first case of a patient with hemophilia who underwent a revision with a tibial
      allograft prosthetic composite without the need for hardware augmentation. CASE
      PRESENTATION: A 43-year-old Caucasian man with a history of hemophilia and
      transfusion-related human immunodeficiency virus and hepatitis B and C presented
      with an interprosthetic fracture of his humerus after months of pain between his
      total elbow and total shoulder arthroplasties. Because of the poor remaining bone
      stock available in his distal humerus, a revision using a barrel-staved tibial
      allograft prosthetic composite was performed. Our patients' factor VIII level was
      optimized before the operation and he suffered no major long-term complications
      at 28 months. His only complication was an incomplete radial nerve palsy that
      ultimately recovered and left him with some numbness on the dorsum of his hand.
      CONCLUSION: Careful use of an allograft prosthetic composite is a very reasonable
      option when a patient experiences an interprosthetic fracture. We have
      successfully performed revision total elbow arthroplasty for a patient with
      hemophilia with an interprosthetic fracture using a tibial allograft and no
      additional fixation, which resulted in his return to full activities of daily
      living, minimal pain and full incorporation of the allograft to host bone.

PMID- 23009282
TI  - Effective treatment of mouse experimental colitis by alpha 2 integrin antibody:
      comparison with alpha 4 antibody and conventional therapy.
AB  - AIM: To compare the therapeutic effect of alpha(2) and alpha(4) integrin-blocking
      antibodies to conventional inflammatory bowel disease drugs methotrexate, 5
      aminosalicylic acid and azathioprine in the dextran sulphate sodium mouse colitis
      model. METHODS: Colitis was induced in balb/c mice with 2.5-3.0% dextran sulphate
      sodium. Treatment was given daily for 7 days after the onset of colitis, by
      rectal installation. Clinical signs of disease were assessed daily using a
      disease activity index. After 19 days, all animals were killed and colon samples
      collected for histological grading and mRNA/protein analysis. All treatment
      groups were compared with an untreated control group and a treatment group
      receiving dextran sulphate sodium alone to monitor the potential degree of
      clinical remission. RESULTS: Treatment with anti-alpha(2) antibodies and
      methotrexate reduced the body weight loss. At the end of treatment, anti-alpha(2)
      antibodies reduced rectal bleeding, while methotrexate reduced the disease
      activity index score. Histological evaluation showed that anti-alpha(2)
      antibodies, methotrexate, 5-aminosalicylic acid and azathioprine treatment
      reduced the acute inflammation; methotrexate was the only treatment with effect
      on the crypt score. Compared with the dextran sulphate sodium alone group, the
      methotrexate group showed down-regulation of IL-1beta at the mRNA level, while
      the anti-alpha(2) antibody group displayed decreased protein expression of iNOS
      and IL-1beta. CONCLUSIONS: Specific blocking of extravascular trafficking of
      leucocytes with alpha(2)-antibodies could be a new beneficial drug target in
      inflammatory bowel disease.

PMID- 23009284
TI  - Factors associated with the presence of multiple Lugol-voiding lesions in
      patients with esophageal squamous-cell carcinoma.
AB  - Multicentric squamous dysplasia of the esophagus is characterized by multiple
      Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are
      associated with a very high risk of multiple cancers arising in the esophagus as
      well as the head and neck. To gain insight into the pathogenesis of multiple LVLs
      of the esophageal mucosa, we studied risk factors for the development of such
      lesions in 76 patients who had a current or previous diagnosis of esophageal
      squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the
      esophageal mucosa. The history of tobacco and alcohol use was documented.
      Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified
      by polymerase chain reaction using sequence-specific primers. Clinical factors
      related to multiple LVLs were analyzed. All patients with multiple LVLs were
      drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence
      interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5,
      95% CI 1.55-13.24: P = 0.006), and smoking index >=1000 (OR 2.6, 95% CI 1.02-6.6:
      P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex
      (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR
      4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among
      drinkers, a daily alcohol intake of >=100 g pure ethanol with the ALDH2-2 allele
      (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure
      ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more
      strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g
      pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of >=100
      g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18)
      did not. In conclusion, male sex and the ALDH2-2 allele are associated with an
      increased risk for multiple LVLs of the esophageal mucosa in patients with
      esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the
      risk of multiple LVLs increased in parallel to the daily alcohol intake. 

PMID- 23009285
TI  - Elution of antimicrobials from a cross-linked dextran gel: In vivo
      quantification.
AB  - REASONS FOR PERFORMING STUDY: Use of a novel, biodegradable, antimicrobial
      impregnated gel provides an alternative method of local treatment of infections
      in horses. OBJECTIVES: To determine in vivo elution of antimicrobial medications
      from antimicrobial-impregnated cross-linked dextran gel and to evaluate the
      effect on wound healing when implanted subcutaneously in horses. METHODS:
      Amikacin-, vancomycin- or amikacin/clindamycin-impregnated gel was placed
      subcutaneously in 11 horses' necks, using 6 replicates with a 3 month washout
      between experiments. Capillary ultrafiltration probes for collection of
      interstitial fluid were placed 0 cm and 1.5 cm from the gel-filled incisions.
      Samples were collected at 0, 4, 8 and 12 h, and on Days 1-10. Blood was collected
      on Days 0, 1 and 7. Amikacin and vancomycin samples were analysed via
      fluorescence polarisation immunoassay, and clindamycin samples via high
      performance liquid chromatography. Histology of biopsy samples was performed at
      the completion of the study. Differences in mean histomorphological scores
      between groups were assessed using Wilcoxon's signed ranks test. RESULTS: Maximum
      antimicrobial concentrations were detected at 4 h (amikacin), and 8 h
      (vancomycin, and amikacin and clindamycin from the combination gel). Mean +/-
      s.d. peak concentrations for amikacin, vancomycin, amikacin
      (amikacin/clindamycin) and clindamycin were 6133 +/- 1461, 7286 +/- 2769, 3948 +/
      317 and 985 +/- 960, respectively. Median number of days for which antimicrobial
      concentration remained above minimum inhibitory concentration for target
      microorganisms at implantation was >=10 days for vancomycin, 9 days (+/- 1) for
      amikacin and 8 days (+/- 1) for clindamycin. Mean plasma amikacin and vancomycin
      concentrations were lower than detectable limits; mean serum clindamycin
      concentrations were 0.52 ug/ml and 0.63 ug/ml at 24 h and 7 days, respectively.
      There were no significant differences in histomorphological scores between
      treatment and control incisions (P>=0.22). CONCLUSIONS AND POTENTIAL RELEVANCE:
      Cross-linked dextran gel is a safe, effective alternative local antimicrobial
      delivery method.

PMID- 23009286
TI  - Self-assembly of LiMo3Se3 nanowire networks from nanoscale building-blocks in
      solution.
AB  - LiMo(3)Se(3) is a highly anisotropic solid comprised of a regular pattern of
      quasi-1-D wire-like structures. Solutions of LiMo(3)Se(3) deposited on substrates
      and TEM grids reveal the presence of two-dimensional network morphologies. High
      resolution STEM imaging reveals that the junctions within these networks are not
      formed by discrete overlying LiMo(3)Se(3) fibers or wires. Rather the junctions
      are continuous in that the wires are seamlessly interwoven from one bundle to the
      next. We investigated network formation by dynamic light scattering and AFM and
      demonstrate that the networks are not pre-existent in solution but rather form
      via self-assembly of nanoscale building blocks that is driven by solvent
      evaporation.

PMID- 23009287
TI  - Kinetic ATR-FTIR studies on phosphate adsorption on iron (oxyhydr)oxides in the
      absence and presence of surface arsenic: molecular-level insights into the ligand
      exchange mechanism.
AB  - The surface chemistry of phosphorus and arsenic compounds in their organic and
      inorganic forms is of great interest to the scientific and industrial communities
      due to its role in controlling their transport, bioaccessibility and speciation.
      We report herein in situ and surface-sensitive rapid kinetic studies on the
      adsorption of phosphate to Fe (oxyhydr)oxides in the presence and absence of
      dimethylarsinic acid (DMA) and arsenate. These studies were conducted at pH 7
      using ATR-FTIR in the flow mode, which were complemented with detailed kinetic
      analysis of the desorption behavior of DMA and arsenate over the same range of
      aqueous [phosphate]. Values for apparent rates of adsorption and desorption were
      extracted from the time dependence of given spectral components characteristic of
      surface phosphate, DMA, or arsenate. Results show that pseudo adsorption rate
      constants of phosphate on Fe (oxyhydr)oxide films increase in this order:
      arsenate-covered < DMA-covered <= freshly prepared. Also, pseudo desorption rate
      constants of DMA complexes are 7-12 times higher than arsenate using phosphate as
      a desorbing agent. When these results are combined with earlier work on the
      thermodynamics, kinetics, and structure of surface complexes, they suggest that,
      during initial times of surface interactions, increasing organic substitution on
      arsenate increases the proportion of relatively weakly bonded complexes
      (monodentate and outer-sphere).

PMID- 23009288
TI  - High density trans-admittance mammography development and preliminary phantom
      tests.
AB  - BACKGROUND: Malignant breast tumor tissue has a significantly different
      electrical impedance spectrum than surrounding normal tissues. This has led to
      the development of impedance imaging as a supplementary or alternative method to
      X-ray mammography for screening and assessment of breast cancers. However low
      spatial resolution and poor signal to noise ratio has limited the clinical
      application. METHODS: In order to improve spatial resolution we developed a trans
      admittance mammography (TAM) system including an array of 60*60 current sensing
      electrodes. We adopted a similar setup to X-ray mammography where the breast is
      situated between two holding plates. The top plate is a large solid metal
      electrode for applying a sinusoidal voltage over a range of frequencies from 50
      Hz to 500 kHz. The bottom plate has 3600 current sensing electrodes that are kept
      at the ground potential. Currents are generated from the top voltage-applying
      electrode and spread throughout the breast, entering the TAM system through the
      array of current sensing electrodes on the bottom plate. The TAM system measures
      the exit currents through 6 switching modules connected to 600 electrodes each.
      Each switching module is connected to 12 ammeter channels which are switched
      sequentially to 50 of the 600 electrodes each measurement time. Each ammeter
      channel is comprised of a current-to-voltage converter, a gain amplifier,
      filters, an analog to digital converter, and a digital phase sensitive
      demodulator. RESULTS: We found an average noise level of 38 nA, amplitude
      stability of less than 0.2%, crosstalk of better than -60 dB and 70 dB signal to
      noise ratio over all channels and operating frequencies. Images were obtained in
      time difference and frequency difference modes in a saline phantom. CONCLUSION:
      We describe the design, construction, and calibration of a high density TAM
      system in detail. Successful high resolution time and frequency difference images
      showed regions of interest with the expected admittivity changes in the frequency
      spectrum.

PMID- 23009289
TI  - Sex differences in microRNA regulation of gene expression: no smoke, just miRs.
AB  - Males and females differ widely in morphology, physiology, and behavior leading
      to disparities in many health outcomes, including sex biases in the prevalence of
      many neurodevelopmental disorders. However, with the exception of a relatively
      small number of genes on the Y chromosome, males and females share a common
      genome. Therefore, sexual differentiation must in large part be a product of the
      sex biased expression of this shared genetic substrate. microRNAs (miRs) are
      small non-coding RNAs involved in the post-transcriptional regulation of up to
      70% of protein-coding genes. The ability of miRs to regulate such a vast amount
      of the genome with a high degree of specificity makes them perfectly poised to
      play a critical role in programming of the sexually dimorphic brain. This review
      describes those characteristics of miRs that make them particularly amenable to
      this task, and examines the influences of both the sex chromosome complement as
      well as gonadal hormones on their regulation. Exploring miRs in the context of
      sex differences in disease, particularly in sex-biased neurodevelopmental
      disorders, may provide novel insight into the pathophysiology and potential
      therapeutic targets in disease treatment and prevention.

PMID- 23009290
TI  - Cefditoren: Comparative efficacy with other antimicrobials and risk factors for
      resistance in clinical isolates causing UTIs in outpatients.
AB  - BACKGROUND: To investigate a possible role of Cefditoren, a recently marketed in
      Greece third-generation oral cephalosporin in urinary infections of outpatients.
      METHODS: During a multicenter survey of Enterobacteriaceae causing UTIs in
      outpatients during 2005-2007, Cefditoren MICs were determined by agar dilution
      method in a randomly selected sample of uropathogens. Susceptibility against 18
      other oral/parenteral antimicrobials was determined according to Clinical and
      Laboratory Standards Institute methodology. RESULTS: A total of 563 isolates (330
      Escherichia coli, 142 Proteus mirabilis and 91 Klebsiella spp) was studied;
      MIC50/MIC90 of Cefditoren was 0.25/0.5 mg/L respectively, with 97.1% of the
      isolates being inhibited at 1 mg/L. All 12 strains producing ESBLs or AmpC
      enzymes were resistant to cefditoren. Susceptibility rates (%) for
      amoxicillin/clavulanic acid, cefuroxime axetil, cefotaxime, ciprofloxacin,
      trimethoprim/sulfamethoxazole and fosfomycin were 93.1- 94.1- 96.8-93.1-71.9 and
      92.8% respectively. Cefditoren MIC was significantly higher in
      nalidixic/ciprofloxacin non-susceptible strains; resistance to cefditoren was not
      associated with resistance to mecillinam, fosfomycin nitrofurantoin and
      aminoglycosides. Multivariate analysis demonstrated history of urinary infection
      in the last two weeks or three months as risk factors for cefditoren resistance.
      CONCLUSIONS: Cefditoren exhibited enhanced in vitro activity against the most
      common uropathogens in the outpatient setting, representing an alternative oral
      treatment option in patients with risk factors for resistance to first-line
      antibiotics.

PMID- 23009291
TI  - Obesity and prostate cancer: gene expression signature of human periprostatic
      adipose tissue.
AB  - BACKGROUND: Periprostatic (PP) adipose tissue surrounds the prostate, an organ
      with a high predisposition to become malignant. Frequently, growing prostatic
      tumor cells extend beyond the prostatic organ towards this fat depot. This study
      aimed to determine the genome-wide expression of genes in PP adipose tissue in
      obesity/overweight (OB/OW) and prostate cancer patients. METHODS: Differentially
      expressed genes in human PP adipose tissue were identified using microarrays.
      Analyses were conducted according to the donors' body mass index characteristics
      (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ
      confined prostate cancer versus benign prostatic hyperplasia). Selected genes
      with altered expression were validated by real-time PCR. Ingenuity Pathway
      Analysis (IPA) was used to investigate gene ontology, canonical pathways and
      functional networks. RESULTS: In the PP adipose tissue of OB/OW subjects, we
      found altered expression of genes encoding molecules involved in adipogenic/anti
      lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes
      (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated).
      Conversely, in the PP adipose tissue of subjects with prostate cancer, altered
      genes were related to adipose tissue cellular activity (increased cell
      proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas
      a downward impact on immunity and inflammation was also observed, mostly related
      to the complement (down-regulation of CFH). Interestingly, we found that the
      microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer
      patients. CONCLUSIONS: Obesity and excess adiposity modified the expression of PP
      adipose tissue genes to ultimately foster fat mass growth. In patients with
      prostate cancer the expression profile of PP adipose tissue accounted for
      hypercellularity and reduced immunosurveillance. Both findings may be liable to
      promote a favorable environment for prostate cancer progression.

PMID- 23009293
TI  - Comparison of optometrist glaucoma referrals against published guidelines.
AB  - PURPOSE: To examine if community optometrists follow published guidelines for
      referral of patients with suspect glaucoma to the hospital eye service. METHODS:
      A retrospective audit of new optometrist-initiated referrals to the Glaucoma
      Service at Moorfields Eye Hospital, London was performed. Clinical data from
      referral letters recorded included evidence of intraocular pressure (IOP)
      measurement and tonometer used. Referral letter information was compared to 2009
      guidelines published jointly by the College of Optometrists and Royal College of
      Ophthalmologists on referring glaucoma suspect patients. RESULTS: A total of 289
      new patients were seen in the Glaucoma Service over a 6 week period from 4th
      January 2011; a 100% hospital record retrieval rate was obtained. Of these, 114
      (39%) were optometrists initiated referrals. Optometrist letters were available
      for 105 patients. IOP measurements were recorded in 102 (97%); most practitioners
      used non-contact tonometry (NCT; n = 69; 68%). Practitioners recorded <4 NCT
      readings per eye (4 readings: n = 3, 4%; 3 readings: n = 42, 61%; 2 readings: n =
      6, 9%; 1 reading: n = 18, 26%). Seventy-seven patients (73%) reported with raised
      IOP as the main referral reason; of these, 33 (43%) were referred with raised IOP
      in isolation. NCT was the instrument used in the majority of these raised IOP
      cases (n = 56; 73%). In cases where raised IOP in isolation was the referral
      reason, 24 (73%) were recorded using NCT; 10 (30%) provided repeat IOP
      measurement data in the letter. One hundred and two (97%) referred patients
      attended the hospital appointment. Thirty (29%) were deemed not to have glaucoma,
      with the remainder diagnosed with ocular hypertension (n = 25; 25%), glaucoma
      suspect/glaucoma (n = 35, 34%) or narrow angles requiring intervention (n = 12,
      12%). Thirty of the 33 patients referred with raised IOP in isolation attended
      their hospital visit. Ten (33%) of these patients were subsequently discharged.
      Six (20%) patients had IOP within normal limits when measured with applanation
      tonometry; all of these patients were kept within the service. CONCLUSIONS:
      Community optometrists using NCT for measurement should be reminded of the
      guidelines on number of readings to take and also the value of repeating NCT
      measures when appropriate. This may help to increase the accuracy of glaucoma
      suspect referrals to hospital eye service.

PMID- 23009292
TI  - Nitric oxide signalling pathway in Duchenne muscular dystrophy mice: up
      regulation of L-arginine transporters.
AB  - DMD (Duchenne muscular dystrophy) is an incurable rapidly worsening neuromuscular
      degenerative disease caused by the absence of dystrophin. In skeletal muscle a
      lack of dystrophin disrupts the recruitment of neuronal NOS (nitric oxide
      synthase) to the sarcolemma thus affecting NO (nitric oxide) production. Utrophin
      is a dystrophin homologue, the expression of which is greatly up-regulated in the
      sarcolemma of dystrophin-negative fibres from mdx mice, a mouse model of DMD.
      Although cardiomyopathy is an important cause of death, little is known about the
      NO signalling pathway in the cardiac muscle of DMD patients. Thus we used
      cardiomyocytes and hearts from two month-old mdx and mdx:utrophin-/- (double
      knockout) mice (mdx:utr) to study key steps in NO signalling: L-arginine
      transporters, NOS and sGC (soluble guanylyl cyclase). nNOS did not co-localize
      with dystrophin or utrophin to the cardiomyocyte membrane. Despite this nNOS
      activity was markedly decreased in both mdx and mdx:utr mice, whereas nNOS
      expression was only decreased in mdx:utr mouse hearts, suggesting that utrophin
      up-regulation in cardiomyocytes maintains nNOS levels, but not function. sGC
      protein levels and activity remained at control levels. Unexpectedly, L-arginine
      transporter expression and function were significantly increased, suggesting a
      novel biochemical compensatory mechanism of the NO pathway and a potential entry
      site for therapeutics.

PMID- 23009294
TI  - Malignancy rates of non-masslike enhancement on breast magnetic resonance imaging
      using American College of Radiology Breast Imaging Reporting and Data System
      descriptors.
AB  - The purpose of this study was to evaluate the malignancy rates for non-masslike
      enhancement on breast magnetic resonance imaging by American College of Radiology
      Breast Imaging Reporting and Data System descriptors. We retrospectively reviewed
      breast magnetic resonance imaging reports with non-masslike enhancement performed
      at Mayo Clinic Florida from April 1, 2003, through March 14, 2007. Each
      descriptor of non-masslike enhancement as per the American College of Radiology
      Breast Imaging Reporting and Data System magnetic resonance lexicon was
      correlated with percutaneous biopsy pathologic results and/or surgical pathologic
      results and follow-up imaging. Positive predictive values were obtained for each
      Breast Imaging Reporting and Data System descriptor. We identified 578 incidents
      of non-masslike enhancement in 378 patients. Of 343 non-masslike enhancements
      that could be correlated with pathology results, 141 (41.1%) were malignant. Of
      the malignant lesions, 53% were found to be ductal carcinoma in situ at
      percutaneous biopsy. Clumped pattern of enhancement and segmental distribution of
      non-masslike enhancement had the highest sensitivities of 40.5% and 23.5%,
      respectively. Asymmetric pattern and segmental distribution had the highest
      positive predictive values of 75.0% and 57.4%, respectively. We concluded that
      the moderate positive predictive values make it difficult to establish guidelines
      for management of non-masslike enhancement and reveal the current limitations of
      breast magnetic resonance imaging.

PMID- 23009295
TI  - Protective effects of glutathione and lipoic acid against cadmium-induced
      oxidative stress in rat's kidney.
AB  - Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the
      mammalian kidney is a major target of Cd-induced toxicity. We analyzed the
      effects of cadmium exposure on the model system of experimental animals, the
      thiobarbituric acid (TBA)-reactive substance (TBARS) level, and the activity of
      xanthine oxidase (XO) and catalase in kidney of rats, with and without
      glutathione and lipoic acid (LA). The experimental animals were classified into
      six groups, regarding cadmium, glutathione, and LA intake. The concentration of
      TBARSs in the homogenate was determined by spectrophotometric method according to
      Nabavi et al. The specific activity of XO was determined spectrophotometrically
      by the method of Aygul et al. Catalase activity in tissues was determined by
      spectrophotometric method according to Nabavi et al. The increased level of TBARS
      and the increased activity of XO in kidney tissue in cadmium poisoning are
      statistically significant compared to control (p < 0.001). Glutathione and LA
      applied along with cadmium lowered TBARS concentration and reduced XO activity (p
      < 0.001). Catalase activity in the kidney tissue was increased in the group,
      which was administered cadmium (p < 0.001). In conclusion, glutathione and LA, as
      physiological antioxidants applied with cadmium, have reduced the level of lipid
      peroxide and the activity of XO, and can be used as protectors in conditions of
      cadmium poisoning.

PMID- 23009296
TI  - Tissue damage and immunity in cutaneous leishmaniasis.
AB  - Cutaneous leishmaniasis (CL) is caused by parasitic infection of dermal
      macrophages resulting in intense immune-mediated tissue inflammation and skin
      ulceration. The severity of the disease is dependent on parasite species as well
      as the immune responses evoked by the host. Most cases of CL heal spontaneously.
      In rare cases, the ulcer/s become chronic, and some Leishmania species may induce
      mucosal leishmaniasis (MCL) leading to severe tissue damage. Due to difficulties
      in obtaining skin tissue, most human studies of CL have been limited to the
      analysis of peripheral blood. While systemic responses may be good correlates of
      immunity, tissue damage and local immune responses at the site of infection is
      seldom reflected in alterations in the peripheral blood. In this review, we
      discuss the different forms of CL focusing on the in situ responses in
      established disease and the mechanisms involved in pathology and healing of
      Leishmania infection. Great effort has been put into animal models dissecting the
      immune events behind the evolution of disease, tissue pathology and parasite
      control. These models of genetically engineered, immune deficient mice or mice
      given therapy prior to onset of overt disease poorly reflect the clinical
      situation, where patients seek treatment once infection is well established.
      Models of established disease are needed to address the clinical challenge of
      identifying new therapeutic targets in treatment CL. Through understanding immune
      deviations during CL potential benefits and risks of emerging biological drugs in
      leishmaniasis can be addressed.

PMID- 23009297
TI  - Microbial biotransformation of kurarinone by Cunninghamella echinulata AS 3.3400.
AB  - In this paper, microbial transformation of kurarinone (1) by Cunninghamella
      echinulata AS 3.3400 was investigated and four transformed products were isolated
      and identified as 6"-hydroxykurarinone (2), 4",5",8"-trihydroxynorkurarinone (3),
      norkurarinone (4), and kurarinone-7-O-beta-glucoside (5), respectively. Among
      them, 3 and 5 are new compounds, and the rare glycosylation in microbial
      transformation was observed. In addition, the cytotoxicities of transformed
      products (2-5) were also investigated.

PMID- 23009298
TI  - The internal dynamics of mini c TAR DNA probed by electron paramagnetic resonance
      of nitroxide spin-labels at the lower stem, the loop, and the bulge.
AB  - Electron paramagnetic resonance (EPR) at 236.6 and 9.5 GHz probed the tumbling of
      nitroxide spin probes in the lower stem, in the upper loop, and near the bulge of
      mini c TAR DNA. High-frequency 236.6 GHz EPR, not previously applied to spin
      labeled oligonucleotides, was notably sensitive to fast, anisotropic, hindered
      local rotational motion of the spin probe, occurring approximately about the NO
      nitroxide axis. Labels attached to the 2'-aminocytidine sugar in the mini c TAR
      DNA showed such anisotropic motion, which was faster in the lower stem, a region
      previously thought to be partially melted. More flexible labels attached to
      phosphorothioates at the end of the lower stem tumbled isotropically in mini c
      TAR DNA, mini TAR RNA, and psi(3) RNA, but at 5  degrees C, the motion became
      more anisotropic for the labeled RNAs, implying more order within the RNA lower
      stems. As observed by 9.5 GHz EPR, the slowing of nanosecond motions of large
      segments of the oligonucleotide was enhanced by increasing the ratio of the
      nucleocapsid protein NCp7 to mini c TAR DNA from 0 to 2. The slowing was most
      significant at labels in the loop and near the bulge. At a 4:1 ratio of NCp7 to
      mini c TAR DNA, all labels reported tumbling times of >5 ns, indicating a
      condensation of NCp7 and TAR DNA. At the 4:1 ratio, pulse dipolar EPR
      spectroscopy of bilabels attached near the 3' and 5' termini showed evidence of
      an NCp7-induced increase in the 3'-5' end-to-end distance distribution and a
      partially melted stem.

PMID- 23009299
TI  - Outpatient-shopping behavior and survival rates in newly diagnosed cancer
      patients.
AB  - OBJECTIVES: To evaluate the appropriateness of the definition of outpatient
      shopping behavior in Taiwanese patients. STUDY DESIGN: Linked study of 3
      databases (Taiwan Cancer Registry, National Health Insurance [NHI] claim
      database, and death registry database). METHODS: Outpatient shopping behavior was
      defined as making at least 4 or 5 physician visits to confirm a cancer diagnosis.
      We analyzed patient-related factors and the 5-year overall survival rate of the
      outpatient-shopping group compared with a nonshopping group. Using the household
      registration database and NHI database, we determined the proportion of
      outpatient shopping, characteristics of patients who did and did not shop for
      outpatient therapy, time between diagnosis and start of regular treatment, and
      medical service utilization in the shopping versus the nonshopping group.
      RESULTS: Patients with higher incomes were significantly more likely to shop for
      outpatient care. Patients with higher comorbidity scores were 1.4 times more
      likely to shop for outpatient care than patients with lower scores. Patients
      diagnosed with more advanced cancer were more likely to shop than those who were
      not. Patients might be more trusting of cancer diagnoses given at higher-level
      hospitals. The nonshopping groups had a longer duration of survival over 5 years.
      CONCLUSIONS: Health authorities should consider charging additional fees after a
      specific outpatient- shopping threshold is reached to reduce this behavior. The
      government may need to reassess the function of the medical sources network by
      shrinking it from the original 4 levels to 2 levels, or by enhancing the referral
      function among different hospital levels.

PMID- 23009300
TI  - Asthma expenditures in the United States comparing 2004 to 2006 and 1996 to 1998.
AB  - OBJECTIVES: To describe how the types of healthcare expenditures for patients
      with asthma have changed over the past decade. STUDY DESIGN: Cross-sectional
      comparison between individuals from 1996 to 1998 and 2004 to 2006. METHODS:
      Expenditures among US individuals (aged 5 to 56 years) with asthma were compared
      using the 1996 to 1998 and the 2004 to 2006 Medical Expenditure Panel Surveys.
      Direct expenditures (medications, inpatient, outpatient, and emergency services)
      and changes in productivity (missed school and work days) were compared over this
      time frame. The adjusted analyses controlled for age, education level,
      race/ethnicity, gender, poverty, region, metropolitan statistical area, self
      reported health, and Charlson Comorbidity Index. RESULTS: Mean annual per capita
      healthcare expenditures increased between 1996 to 1998 and 2004 to 2006 ($3802 vs
      $5322 inflated to 2010 US dollars, P <.0001). Annual medication expenditures
      doubled from $974 to $2010 per person (P <.0001) and outpatient visit
      expenditures increased from $861 to $1174 (P <.0001) while hospitalization and
      emergency department (ED) visit expenditures were similar over the same time
      period. Missed school and work days decreased between the 2 periods (9.23 days in
      1996-1998 vs 6.39 days in 2004-2006, P = .001). CONCLUSIONS: An increase in total
      direct expenditures in individuals with asthma was largely driven by an increase
      in spending on medications comparing 2004 to 2006 and 1996 to 1998 data. However,
      this increase was not offset by lower spending on hospitalization and ED visits.

PMID- 23009302
TI  - Impact of a managed controlled-opioid prescription monitoring program on care
      coordination.
AB  - INTRODUCTION: Inappropriate opioid medication utilization has grown tremendously
      in recent years. Managed care organizations have the opportunity to identify
      potential opioid misuse and implement care coordination interventions. METHODS:
      This randomized controlled study evaluated the impact of providing actionable
      information to prescribers of members who received opioid prescriptions from 3 or
      more prescribers at 3 or more pharmacies in a 3-month identification period.
      Impact was assessed through change in number of prescribers, dispensing
      pharmacies, and filled opioid prescriptions over a 1-year period following
      identification. RESULTS: Members randomly assigned to the intervention group
      demonstrated greater reductions in the number of prescribers (23.98%), dispensing
      pharmacies (16.28%), and filled opioid prescriptions (15.25%) over the 1-year
      period. Regression analyses identified group assignment and the number of opioid
      prescribers in the 3-month identification period as statistically significant
      predictors of reductions in the number of prescribers, pharmacies, and filled
      prescriptions. CONCLUSIONS: This intervention provided action-able information to
      prescribers regarding member opioid utilization, in addition to available managed
      care resources. It resulted in significantly greater reductions in the number of
      prescribers, pharmacies, and prescriptions compared with a general information
      letter notifying prescribers of available managed care resources. Implementation
      of this intervention has the potential to enhance coordination of care for
      members potentially at risk for poor health outcomes.

PMID- 23009301
TI  - Impact of clinical complexity on the quality of diabetes care.
AB  - OBJECTIVES: To assess the impact of clinical complexity on 3 dimensions of
      diabetes care. STUDY DESIGN: We identified 35,872 diabetic patients receiving
      care at 7 Veterans Affairs facilities between July 2007 and June 2008 using
      administrative and clinical data. We examined control at index and appropriate
      care (among uncontrolled patients) within 90 days, for blood pressure (<130/80 mm
      Hg), glycated hemoglobin (<7%), and low-density lipoprotein cholesterol (<100
      mg/dL). We used ordered logistic regression to examine the impact of complexity,
      defined by comorbidities count and illness burden, on control at index and a
      combined measure of quality (control at index or appropriate follow-up care) for
      all 3 measures. RESULTS: There were 6260 (17.5%) patients controlled at index for
      all 3 quality indicators. Patients with >3 comorbidities (odds ratio [OR], 1.94;
      95% confidence interval [CI], 1.67-2.26) and illness burden >2.00 (OR, 1.22; 95%
      CI, 1.13-1.32) were more likely than the least complex patients to be controlled
      for all 3 measures. Patients with >3 comorbidities (OR, 2.30; 95% CI, 2.07-2.54)
      and illness burden >2.00 (OR, 1.25; 95% CI, 1.18-1.33) were also more likely than
      the least complex patients to meet the combined quality indicator for all 3
      measures. CONCLUSIONS: Patients with greatest complexity received higher quality
      diabetes care compared with less complex patients, regardless of the definition
      of complexity chosen. Although providers may appropriately target complex
      patients for aggressive control, deficits in guideline achievement among all
      diabetic patients highlight the challenges of caring for chronically ill patients
      and the importance of structuring primary care to promote higher-quality, patient
      centered care.

PMID- 23009303
TI  - State-level projections of cancer-related medical care costs: 2010 to 2020.
AB  - BACKGROUND: As the population ages, the financial amount spent on cancer care is
      expected to increase substantially. In this study, we projected cancer-related
      medical costs by state from 2010 through 2020. METHODS: We used pooled Medical
      Expenditure Panel Survey data for 2004 to 2008 and US Census Bureau population
      projections to produce state-level estimates of the number of people treated for
      cancer and the average cost of their treatment, from a health system perspective,
      by age group (18-44, 45-64, >65 years) and sex. In the base model, we assumed
      that the percentage of people in each of the 6 age-by-sex categories who had been
      treated for cancer would remain constant and that the inflation-adjusted average
      cancer treatment cost per person would increase at the same rate as Congressional
      Budget Office projections of overall medical spending. RESULTS: We projected that
      state-level cancer-related medical costs would increase by 34% to 115% (median =
      72%) and that state-level costs in 2020 would range from $347 million to $28.3
      billion in 2010 dollars (median = $3.7 billion). CONCLUSIONS: The number of
      people treated for cancer and the costs of their cancer-related medical care are
      projected to increase substantially for each state. Effective prevention and
      early detection strategies are needed to limit the growing burden of cancer.

PMID- 23009304
TI  - Impact of medical homes on quality, healthcare utilization, and costs.
AB  - OBJECTIVES: To assess baseline quality metrics, healthcare utilization, and costs
      of commercially insured patients treated at practices participating in a patient
      centered medical home (PCMH) pilot. STUDY DESIGN: Observational cohort study
      utilizing claims data for patients treated at PCMH and non-PCMH practices.
      METHODS: Data from Empire Blue Cross and Blue Shield, 1 of 14 plans in the
      HealthCore Integrated Research Database, were queried for patients identified
      based on visits to PCMH and non-PCMH practices during 2007-2008; outcome metrics
      were formulated from the baseline calendar year, 2009. Differences in healthcare
      utilization were determined with x(2) and 2-sample t tests. Regression models
      were used to test differences in adjusted emergency department (ED) use,
      inpatient services, and costs. RESULTS: The study included 31,032 PCMH and
      350,015 non-PCMH patients. Among PCMH-treated patients, diabetics had higher
      rates of glycated hemoglobin testing; cardiovascular disease patients had higher
      rates of testing and better low-density lipoprotein cholesterol control; imaging
      rates for low back pain were lower; among pediatric patients, inappropriate
      antibiotic use for nonspecific or viral respiratory infections was lower. PCMH
      treated adults and children had 12% and 23% lower odds of hospitalization, and
      required 11% and 17% fewer ED services, respectively, than non-PCMH patients.
      Risk-adjusted total per member per month costs were 8.6% and 14.5% lower for PCMH
      treated pediatric and adult patients, respectively (P <.01). CONCLUSIONS: PCMH
      practices in this pilot were associated with better preventive health, higher
      levels of disease management, and lower resource utilization and costs in 2009
      compared with practices not pursuing PCMH status.

PMID- 23009305
TI  - Competitive bidding in Medicare: who benefits from competition?
AB  - OBJECTIVES: To conduct the first empirical study of competitive bidding in
      Medicare. STUDY DESIGN AND METHODS: We analyzed 2006-2010 Medicare Advantage data
      from the Centers for Medicare and Medicaid Services using longitudinal models
      adjusted for market and plan characteristics. RESULTS: A $1 increase in
      Medicare's payment to health maintenance organization (HMO) plans led to a $0.49
      (P <.001) increase in plan bids, with $0.34 (P <.001) going to beneficiaries in
      the form of extra benefits or lower cost sharing. With preferred provider
      organization and private fee-for-service plans included, higher Medicare payments
      increased bids less ($0.33 per dollar), suggesting more competition among these
      latter plans. CONCLUSIONS: As a market-based alternative to cost control through
      administrative pricing, competitive bidding relies on private insurance plans
      proposing prices they are willing to accept for insuring a beneficiary. However,
      competition is imperfect in the Medicare bidding market. As much as half of every
      dollar in increased plan payment went to higher bids rather than to
      beneficiaries. While having more insurers in a market lowered bids, the design of
      any bidding system for Medicare should recognize this shortcoming of competition.

PMID- 23009306
TI  - Medication adherence and Medicare expenditure among beneficiaries with heart
      failure.
AB  - OBJECTIVES: To (1) measure utilization of and adherence to heart failure
      medications and (2) assess whether better adherence is associated with lower
      Medicare spending. STUDY DESIGN: Pooled cross-sectional design using six 3-year
      cohorts of Medicare beneficiaries with congestive heart failure (CHF) from 1997
      through 2005 (N = 2204). METHODS: Adherence to treatment was measured using
      average daily pill counts. Bivariate and multivariate methods were used to
      examine the relationship between medication adherence and Medicare spending.
      Multivariate analyses included extensive variables to control for confounding,
      including healthy adherer bias. RESULTS: Approximately 58% of the cohort were
      taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor
      blocker (ARB), 72% a diuretic, 37% a beta-blocker, and 34% a cardiac glycoside.
      Unadjusted results showed that a 10% increase in average daily pill count for ACE
      inhibitors or ARBs, beta-blockers, diuretics, or cardiac glycosides was
      associated with reductions in Medicare spending of $508 (not significant [NS]),
      $608 (NS), $250 (NS), and $1244 (P <.05), respectively. Estimated adjusted
      marginal effects of a 10% increase in daily pill counts for beta-blockers and
      cardiac glycosides were reductions in cumulative 3-year Medicare spending of $510
      to $561 and $750 to $923, respectively (P <.05). CONCLUSIONS: Higher levels of
      medication adherence among Medicare beneficiaries with CHF were associated with
      lower cumulative Medicare spending over 3 years, with savings generally exceeding
      the costs of the drugs in question.

PMID- 23009308
TI  - Talking science and wishing for miracles: understanding cultures of mental health
      practice.
AB  - Science can only offer a limited account of, and prescription for, mental health
      care. Yet the language of science and faith in the universal applicability of
      particular scientific methods to the craft of mental health care has come to
      permeate mental health practice communities. In this paper, the argument that
      many beliefs held by mental health professionals might be considered to be based
      on faith rather than science is presented, and the view that culture provides a
      useful lens for understanding mental health services and these paradoxes is
      proposed. Clearly there is a grand mental health narrative or colonizing
      influence of biological psychiatry that in various ways affects all mainstream
      mental health services. Local health services and professional communities might
      be considered subcultures. Understanding how mental health professions and
      practice are embedded in culture might be useful in considering how practice
      changes and why. Culture and caring practices are mutually embedded in localized
      subcultures. Therefore, a rich description of context and history is necessary in
      publication, presentation, or other communications to enable genuine
      understanding by a global audience. Viewing mental health practice in a cultural
      context highlights the importance of values and differences, and encourages
      humility in the face of ambiguity.

PMID- 23009307
TI  - Picosecond to second dynamics reveals a structural transition in Clostridium
      botulinum NO-sensor triggered by the activator BAY-41-2272.
AB  - Soluble guanylate cyclase (sGC) is the mammalian endogenous nitric oxide (NO)
      receptor that synthesizes cGMP upon NO activation. In synergy with the artificial
      allosteric effector BAY 41-2272 (a lead compound for drug design in
      cardiovascular treatment), sGC can also be activated by carbon monoxide (CO), but
      the structural basis for this synergistic effect are unknown. We recorded in the
      unusually broad time range from 1 ps to 1 s the dynamics of the interaction of CO
      binding to full length sGC, to the isolated sGC heme domain beta(1)(200) and to
      the homologous bacterial NO-sensor from Clostridium botulinum. By identifying all
      phases of CO binding in this full time range and characterizing how these phases
      are modified by BAY 41-2272, we show that this activator induces the same
      structural changes in both proteins. This result demonstrates that the BAY 41
      2272 binding site resides in the beta(1)(200) sGC heme domain and is the same in
      sGC and in the NO-sensor from Clostridium botulinum.

PMID- 23009309
TI  - Effects of feeding pistachio by-products silage on growth performance, serum
      metabolites and urine characteristics in Holstein male calves.
AB  - This study investigated physiological effects of pistachio by-products silage
      (PBPS) substituted in Holstein male calves diets and its effects on the growth
      performance. Twenty-four Holstein male calves (4-5 months of age and 155.6 +/-
      13.5 kg BW) were randomly assigned to one of four experimental diets (n = 6);
      contained 0%, 6%, 12% and 18% of PBPS (DM basis) respectively. During a 6-month
      experiment, dry matter intake (DMI) and weight gain were recorded and blood and
      urine samples were collected at different times. Results showed that mean DMI was
      not affected by different levels of PBPS in diets. But the calves fed 6% PBPS had
      the highest average daily gain (p < 0.05) and the lowest feed conversion ratio (p
      < 0.05). The calves fed 12% and 18% PBPS had lower albumin, white blood cell,
      haemoglobin and packed cell volume (p < 0.05) than those fed other diets.
      However, other serum metabolites, complete blood count (CBC), insulin and liver
      enzymes were not affected by the experimental diets. The long-term feeding of
      PBPS at different levels had no significant effect (p > 0.05) on pH, specific
      gravity, the number of white and red blood cells and epithelial cells count in
      urine. The animals did not show any symptom of illness or toxicity during the
      experimental period and all of the blood and urine parameters were in a normal
      range. It was concluded that substitution of PBPS up to 18% of the total diet
      that provide up to 18.2 g/kg DM total tannin had no adverse effects for Holstein
      male calves. 

PMID- 23009310
TI  - Use of near-infrared spectroscopy as a measure of cerebrovascular health in aging
      adults.
AB  - Neuroimaging techniques assessing oxygenation of cerebral blood (such as near
      infrared spectroscopy, NIRS) may reflect general cerebrovascular health, a factor
      not always considered in studies comparing younger and older adults. We examined
      whether baseline dorsolateral prefrontal cerebral oxygenation (measured by NIRS)
      was related to cardiovascular risk factors and cognitive test performance in
      healthy older adults. We found that cardiovascular risk factors are associated
      with both baseline dorsolateral prefrontal cortex cerebral oxygenation and memory
      performance. In addition, cardiovascular health factors were associated with
      memory performance, and the relationship between cerebral oxygenation and memory
      performance was explained by these cardiovascular health factors, supporting our
      contention that NIRS can reflect general cerebrovascular health in older adults.
      Results suggest that studies examining differences in cortical activation in
      older and younger adults should consider the potential confound of cardiovascular
      and cerebrovascular health when interpreting data from imaging methods based on
      oxygenated cerebral blood flow.

PMID- 23009311
TI  - An urea, arginine and carnosine based cream (Ureadin Rx Db ISDIN) shows greater
      efficacy in the treatment of severe xerosis of the feet in Type 2 diabetic
      patients in comparison with glycerol-based emollient cream. A randomized,
      assessor-blinded, controlled trial.
AB  - BACKGROUND: Xerosis is a common skin disorder frequently observed in diabetic
      patients. An effective hydration of foot skin in diabetics is a relevant
      preventive strategy in order to maintain a healthy foot. Urea is considered an
      effective hydrating and emollient topical product. The aim of the present study
      was to evaluate the efficacy of topical urea 5% with arginine and carnosine
      (Ureadin Rx Db, ISDIN Spain) (UC) in comparison with glycerol-based emollient
      topical product (Dexeryl, Pierre Fabre) (EC), in Type 2 diabetic patients.
      METHODS: We assessed the effect of UC on skin hydration in a randomized,
      evaluator-blinded comparative study in 40 type II diabetic patients, aged 40-75
      years, treated with UC or the comparator for 28 days with a twice-daily
      application. The principal outcomes were the Dryness Area Severity Index (DASI)
      Score and the Visual Analogue Score (VAS) for skin dryness evaluated at baseline
      and at the end of study period by an investigator unaware of treatment
      allocation. RESULTS: UC induced significantly greater hydration than EC with an
      89% reduction in DASI score (from 1.6 to 0.2; p < 0.001) in comparison with
      baseline values. After 4 weeks, compared with the control group, DASI score in UC
      treated group was significantly lower (0.2 vs. 1.0; p = 0.048). VAS score (high
      values mean better hydration) significantly increased in both groups during
      treatment. VAS score at the end of treatment period was significantly higher in
      UC group in comparison with EC group (9.8 vs. 8.2; p = 0.05). CONCLUSION:
      Application of urea 5%, arginine and carnosine cream increases skin hydration and
      alleviates the condition of skin dryness in Type 2 diabetic patients in
      comparison with a control glycerol-based emollient product. (Dutch Trials
      Register trial number 3328).

PMID- 23009312
TI  - Professor Mitsuru Hashida: his outstanding achievements in drug delivery
      research.

PMID- 23009313
TI  - Combining proton and electron transfer to modulate the stability of
      cucurbit[7]uril complexes.
AB  - (Ferrocenylmethyl)methylammonium (1H(+)) is an excellent cationic guest for
      inclusion complexation by the cucurbit[7]uril host. However, deprotonation of the
      guest leads to a decrease of 14.8 kJ mol(-1) in the overall stability of its
      inclusion complex, and one-electron oxidation of the guest's ferrocene residue
      further diminishes the complex stability by another 12.3 kJ mol(-1). Overall,
      guest deprotonation followed by its oxidation constitutes an accessible method to
      lower the equilibrium association constant for the CB7.1H(+) complex by more than
      4 orders of magnitude.

PMID- 23009314
TI  - Giant deep orbital dermoid cyst presenting early in infancy in a Nigerian child:
      a case report and review of the literature.
AB  - INTRODUCTION: Dermoid cysts are the most common orbital cystic lesions seen in
      children. While superficial orbital dermoid cysts present early in life, deep
      dermoid cysts remain clinically occult until adolescence or adulthood. We here
      present a case of a deep orbital dermoid cyst in a Nigerian child that became
      symptomatic early in infancy. CASE PRESENTATION: A female Nigerian infant of
      Yoruba ethnicity presented at three months of age with left non-axial proptosis
      and a hazy cornea. A superotemporal cystic orbital mass was seen on
      ultrasonography, and her parents were counseled for simple tumor excision. They
      however defaulted, only for their child to re-present two years later with
      gradually progressive proptosis, an enlarged orbit and keratinized ocular
      surface, necessitating orbital exenteration. CONCLUSION: Deep orbital dermoid
      cysts may be symptomatic from birth. Late presentation may result in an
      irreversible loss of vision, as demonstrated in our case. The need for public
      enlightenment on early presentation and prompt management of such benign lesions
      is emphasized.

PMID- 23009316
TI  - Infrared spectra of M-eta2-C2H2, HM-C=CH, and HM-C=CH- prepared in reactions of
      laser-ablated group 3 metal atoms with acetylene.
AB  - The major HM-C=CH and M-eta(2)-C(2)H(2) products are observed in the matrix
      infrared spectra from reactions of laser-ablated group 3 metal atoms with
      acetylene, while the vinylidene product is not detected. These results reveal
      that coordination of group 3 metal atoms to the acetylene pi-bond and H-migration
      from C to M readily occur during codeposition and photolysis afterward. The
      product absorption assigned to the La-vinylidene complex in a previous study is
      reassigned to one of the absorptions of La-eta(2)-C(2)H(2)...C(2)H(2). Two strong
      Sc-H stretching absorptions are assigned to the free HSc-CCH(-) anion, in accord
      with a previous study, but a lower frequency counterpart is reassigned to HSc
      CCH(-) coordinated to acetylene based on the increasing relative intensity of the
      low-frequency component at higher acetylene concentration. The group 3 metals
      evidently form weaker pi-complexes than the group 4 metals. The addition of an
      electron to HM-CCH elongates the M-H and M-C bonds in the anionic species due to
      the lower ionic contributions to the bonding.

PMID- 23009315
TI  - Three-dimensional measurement of foot arch in preschool children.
AB  - BACKGROUND: The prevalence of flexible flatfoot is high among preschool-aged
      children, but the effects of treatment are inconclusive due to the unclear
      definitions of normal flatfoot. To date, a universally accepted evaluation method
      of the foot arch in children has not been completely established. Our aims of
      this study were to establish a new method to evaluate the foot arch from a three
      dimensional perspective and to investigate the flexibility of the foot arch among
      children aged from two to six. METHODS: A total of 44 children aged from two to
      six years of age were put into five age groups in this study. The navicular
      height was measured with one leg standing, and both feet were scanned separately
      in both sitting and one leg standing positions to compute the foot arch volume.
      The arch volume index, which represents the ratio of the difference in volume
      between sitting and one leg standing positions to the volume when sitting was
      calculated to demonstrate the flexibility of the foot arch. The differences of
      measured parameters between each aged group were analyzed by one-way ANOVA.
      RESULTS: The arch volumes when sitting and standing were highly correlated with
      the navicular height. The navicular height ranged from 15.75 to 27 mm, the arch
      volume when sitting ranged from 6,223 to 11,630 mm3, and the arch volume when
      standing from 3,111 to 7,848 mm3 from two to six years of age. The arch volume
      index showed a declining trend as age increased. CONCLUSION: This study is the
      first to describe the foot arch with volume perspective in preschool-aged
      children. The foot arch volume was highly correlated with the navicular height.
      Research results show both navicular height index and arch volume index gradually
      increase with age from two to six. At the same time the arch also becomes rigid
      with age from two to six. These results could be applied for clinical evaluation
      of the foot arch and post-treatment evaluation.

PMID- 23009317
TI  - Benchmarking HIV health care: from individual patient care to health care
      evaluation. An example from the EuroSIDA study.
AB  - BACKGROUND: State-of-the-art care involving the utilisation of multiple health
      care interventions is the basis for an optimal long-term clinical prognosis for
      HIV-patients. We evaluated health care for HIV patients based on four key
      indicators. METHODS: Four indicators of health care were assessed: Compliance
      with current guidelines on initiation of: 1) combination antiretroviral therapy
      (cART); 2) chemoprophylaxis; 3) frequency of laboratory monitoring; and 4)
      virological response to cART (proportion of patients with HIV-RNA < 500copies/ml
      for >90% of time on cART). RESULTS: 7097 EuroSIDA patients were included from
      Northern (n = 923), Southern (n = 1059), West Central (n = 1290) East Central (n
      = 1366), Eastern (n = 1964) Europe, and Argentina (n = 495). Patients in Eastern
      Europe with a CD4 < 200cells/mm(3) were less likely to initiate cART and
      Pneumocystis jiroveci-chemoprophylaxis compared to patients from all other
      regions, and less frequently had a laboratory assessment of their disease status.
      The proportion of patients with virological response was highest in Northern, 89%
      vs. 84%, 78%, 78%, 61%, 55% in West Central, Southern, East Central Europe,
      Argentina and Eastern Europe, respectively (p < 0.0001). Compared to Northern,
      patients from other regions had significantly lower odds of virological response;
      the difference was most pronounced for Eastern Europe and Argentina (adjusted OR
      0.16 [95%CI 0.11-0.23, p < 0.0001]; 0.20[0.14-0.28, p < 0.0001] respectively).
      CONCLUSIONS: This assessment of HIV health care utilization revealed pronounced
      regional differences in adherence to guidelines and can help to identify gaps and
      direct target interventions. It may serve as a tool for the assessment and
      benchmarking of the clinical management of HIV patients in any setting worldwide.

PMID- 23009318
TI  - Distinction between persistent and transient infection in a bovine viral
      diarrhoea (BVD) control programme: appropriate interpretation of real-time RT-PCR
      and antigen-ELISA test results.
AB  - Control of bovine viral diarrhoea (BVD) in Belgium is currently implemented on a
      voluntary basis at herd level and mainly relies on detection and culling of
      persistently infected (PI) animals. The present field study was conducted during
      the winter of 2010/2011 to assess the performances of diagnostic assays used in
      the testing scheme for BVD as proposed by the two Belgian regional laboratories.
      Individual blood samples were collected from 4972 animals, and individual samples
      from the same herd were pooled (maximum of 30 individual samples per pool) and
      screened for the presence of Bovine Viral Diarrhoea Virus (BVDV)-specific RNA
      using a commercial real-time RT-PCR test (ADIAGENE). Individual samples from
      positive pools were then tested in parallel with the same RT-PCR test and with an
      antigen-capture ELISA test (IDEXX) to detect viremic animals. This study
      demonstrated that individual results differed according to the type of assay used
      (P < 0.001): 140 animals (2.8%) were positive by RT-PCR and 72 (1.4%) by antigen
      ELISA. A second blood sample was taken 40 days later from 74 PCR positive animals
      to detect persistent viremia: 17 (23%) of these were still PCR positive and
      considered to be PI and the 57 that no longer tested positive were assumed to be
      transiently infected (TI) animals. All PI animals were positive also by antigen
      ELISA at both time points. Among TI animals, 10 (16%) were positive by antigen
      ELISA at the first but none at the second sampling. A highly significant
      difference in cycle threshold (Ct ) values obtained by RT-PCR was observed
      between PI and TI animals. ROC analysis was performed to establish thresholds to
      confirm with high probability that an animal is PI, based on the result of RT-PCR
      test performed on a single individual blood sample. 

PMID- 23009319
TI  - Invasive fungal diseases in haematopoietic cell transplant recipients and in
      patients with acute myeloid leukaemia or myelodysplasia in Brazil.
AB  - Invasive fungal disease (IFD) shows distinct regional incidence patterns and
      epidemiological features depending on the geographic region. We conducted a
      prospective survey in eight centres in Brazil from May 2007 to July 2009. All
      haematopoietic cell transplant (HCT) recipients and patients with acute myeloid
      leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year
      (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative
      incidence (CI) of proven or probable IFD was calculated, and curves were compared
      using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378
      allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and
      autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23
      episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the
      most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS,
      allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%,
      3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%,
      and was lower in cases of fusariosis (41%). We observed a high burden of IFD and
      a high incidence and mortality for fusariosis in this first multicentre
      epidemiological study of IFD in haematological patients in Brazil.

PMID- 23009320
TI  - Is methane a new therapeutic gas?
AB  - BACKGROUND: Methane is an attractive fuel. Biologically, methanogens in the colon
      can use carbon dioxide and hydrogen to produce methane as a by-product. It was
      previously considered that methane is not utilized by humans. However, in a
      recent study, results demonstrated that methane could exert anti-inflammatory
      effects in a dog small intestinal ischemia-reperfusion model. POINT OF VIEW:
      Actually, the bioactivity of methane has been investigated in gastrointestinal
      diseases, but the exact mechanism underlying the anti-inflammatory effects is
      required to be further elucidated. Methane can cross the membrane and is easy to
      collect due to its abundance in natural gas. Although methane is flammable,
      saline rich in methane can be prepared for clinical use. These seem to be good
      news in application of methane as a therapeutic gas. CONCLUSION: Several problems
      should be resolved before its wide application in clinical practice.

PMID- 23009321
TI  - Breast cancer recurrence after inadvertent malpositioning of a partial breast
      radiation catheter.
AB  - Accelerated partial breast irradiation (APBI) is an alternative to receiving
      whole breast radiation in carefully selected patients. Because breast cancer
      local recurrence rates are low and follow-up has been short-term, the exact cause
      of recurrences after APBI has been difficult to evaluate. We report the first
      case of documented radiation balloon catheter malpositioning that resulted in
      local recurrence. Patients undergo CT imaging of the breast after radiation
      balloon catheter placement for radiotherapy treatment planning, which evaluates
      adequate conformance of the balloon to the surrounding breast parenchyma and
      confirms a >7 mm distance between the balloon surface and the skin surface.
      Although true local recurrences are rare in appropriately selected partial breast
      irradiation candidates, inadvertent malpositioning of the radiation treatment
      catheter can increase the risk. This case is presented to illustrate the
      importance of comparing CT radiation planning images, with treatment catheter in
      place, to the original diagnostic breast imaging studies to confirm proper
      catheter positioning (in addition to measuring balloon to skin distance and
      conformance) prior to initiating radiotherapy.

PMID- 23009322
TI  - Equine bone marrow-derived mesenchymal stromal cells (BMDMSCs) from the ilium and
      sternum: are there differences?
AB  - REASONS FOR PERFORMING STUDY: The 2 sites of bone marrow harvest for isolation of
      mesenchymal stromal cells (MSC) in the horse are the sternum and ilium. The
      technical procedure is based on practitioner preference, but no studies have
      compared MSC concentrations and growth rates between the sites in horses aged 2-5
      years. OBJECTIVES: The objective of this study was to compare nucleated cell
      counts and growth rates between the sternum and ilium and between consecutive 5
      ml bone marrow aspirates. We hypothesised that there would be a higher
      concentration of MSCs in the sternum than the ilium, and that the first
      sequential aspirate from either site would yield the greatest concentration of
      MSCs. We hypothesised that growth rates of cells from each site would not differ.
      METHODS: Seven horses, aged 2 to 5 years, had 2 sequential 5 ml marrow aspirates
      taken from the sternum and ilium. Nucleated cell counts (NCCs) were obtained
      before and after marrow processing. Cells were expanded in culture for 3 passages
      and growth rate characteristics compared for all aspirates. RESULTS: The NCCs of
      the first 5 ml aspirate were higher than those of the second 5 ml aspirate for
      both sites (P<0.05). There was no difference between growth rates for any of the
      groups (P>0.05). CONCLUSIONS: The NCCs and growth rates of progenitor cells in
      the ilium and sternum are similar for horses in the 2-5 year age category. The
      first 5 ml bone marrow aspirate has a higher concentration of NCCs and resulting
      bone marrow-derived MSC population than subsequent aspirates. POTENTIAL
      RELEVANCE: The first 5 ml aspirates from the sternum and ilium offer a rich
      supply of bone marrow-derived MSCs with similar growth rate characteristics. The
      harvesting procedure of only a 5 ml draw from either the sternum or ilium should
      result in adequate numbers of MSCs.

PMID- 23009323
TI  - Hyperbaric oxygen therapy alleviates oxidative stress and tissue injury in renal
      ischemia/reperfusion injury in rats.
AB  - Hyperbaric oxygen (HBO) therapy has been shown to attenuate renal
      ischemia/reperfusion (I/R) injury in rats, when applied in the early reperfusion
      period. The aim of this study was to elucidate possible beneficial effects of HBO
      therapy on renal I/R injury, when applied 24 h after ischemia. Rats were
      randomized into three groups: (1) control group (n = 20), (2) I/R group (n = 20),
      and (3) I/R + HBO group (n = 20). Renal I/R injury was created by interrupting
      renal blood flow for 30 min with a non-traumatic vascular clamp. HBO therapy was
      administered 24 h after I/R injury and continued for 5 days. At the end of the
      study, rats were sacrificed under anesthesia, blood was drawn, and right kidneys
      were harvested for analysis. Renal I/R injury increased serum and tissue
      malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) levels. HBO therapy attenuated MDA levels by
      increasing SOD and GPx activities. HBO therapy also prevented neutrophil
      infiltration and tissue injury in kidneys. Taken together, HBO therapy has been
      found to be effective in the delayed period of I/R injury.

PMID- 23009324
TI  - Influence of central corneal thickness on measured intraocular pressure
      differentials: Nidek RKT-7700, Topcon CT-80 NCTs and Goldmann Tonometer.
AB  - PURPOSE: We sought to compare the intraocular pressure (IOP) measured by RKT-7700
      and CT-80 noncontact tonometers (NCTs) with that measured by Goldmann applanation
      tonometry (GAT). We also examined the influence of central corneal thickness
      (CCT) on the agreement between both NCTs and GAT in a sub-population of healthy,
      young normals. METHODS: Triplicate IOP and CCT measurements were obtained twice
      from one randomized eye of 49 subjects (28 males and 21 females) aged 22.2 +/-
      1.3 (mean +/- S.D.) years. Goldmann tonometry was performed subsequent to
      assessment with the RKT-7700 and CT-80, to negate the 'ocular massage effect',
      followed by ultrasound pachymetry. The results from each method were compared and
      assessed for repeatability and between-observer reproducibility. Analysis was
      performed to determine the correlation between the differences in IOP
      measurements and corneal thicknesses. RESULTS: The mean differences (+/-S.D.) in
      sessions 1 and 2 respectively between RKT-7700 and GAT (2.6 +/- 2.0 and 2.7 +/-
      1.4 mmHg), between CT-80 and GAT (2.8 +/- 2.0 and 3.2 +/- 1.3 mmHg) were
      statistically significant (p < 0.0001). The repeatability coefficients in
      sessions 1 and 2 respectively were; +/-1.2 and +/-1.0 mmHg (GAT), +/-1.3  and +/
      1.6 mmHg (CT-80), +/-2.3  and +/-1.7 mmHg (RKT-7700) and inter-observer
      reproducibility was; +/-1.9 (RKT-7700), +/-2.3 (GAT) and +/-2.6 mmHg (CT-80).
      Between the corneal thickness and the differences in GAT-measured and NCT
      measured IOPs, there was a significant negative correlation and a trend for a
      larger difference in thicker corneas. CONCLUSION: Neither the RKT-7700 nor the CT
      80 can be used interchangeably with the Goldmann tonometer, although all three
      tonometers give repeatable measurements of IOP, in this sub-population. IOP
      differences between GAT and the NCTs significantly correlated with CCT, with the
      possibility of even greater differences in thicker corneas.

PMID- 23009325
TI  - The relationship between obesity and prostate cancer: from genetics to disease
      treatment and prevention.
AB  - Recent studies demonstrated that obesity is associated with prostate cancer
      aggressiveness and prognosis. However, the mechanisms underlying this
      relationship are poorly understood. Tumor microenvironment has been increasingly
      considered as an important determinant of cancer growth and progression. In the
      light of this growing evidence, Ribeiro et al., in a BMC Medicine research
      article, investigated the gene expression profiles of periprostatic adipose
      tissue of obese patients with and without prostate cancer and compared them to
      those of lean patients. Their findings provide the first evidence of a
      differential gene expression in the periprostatic adipose tissue of obese
      individuals. Differences were also observed when comparing the periprostatic
      adipose tissue of patients with and without prostate cancer. Differentially
      expressed genes are related to cell proliferation and immunological responses.
      Besides suggesting the genetic bases for the observed relationship between
      obesity and prostate cancer aggressiveness, these findings provide new insights
      on the important link between local microenvironment and cancer progression.

PMID- 23009326
TI  - Correlating conformational shift induction with altered inhibitor potency in a
      multidrug resistant HIV-1 protease variant.
AB  - Inhibitor-induced conformational ensemble shifts in a multidrug resistant HIV-1
      protease variant, MDR769, are characterized by site-directed spin labeling double
      electron-electron resonance spectroscopy. For MDR769 compared to the native
      enzyme, changes in inhibitor IC(50) values are related to a parameter defined as
      |DeltaC|, which is the relative change in the inhibitor-induced shift to the
      closed state. Specifically, a linear correlation is found between |DeltaC| and
      the magnitude of the change in IC(50), provided that inhibitor binding is not too
      weak. Moreover, inhibitors that exhibit MDR769 resistance no longer induce a
      strong shift to a closed conformational ensemble as seen previously in the native
      enzyme.

PMID- 23009327
TI  - An ABC transporter with two periplasmic binding proteins involved in iron
      acquisition in Pseudomonas aeruginosa.
AB  - Pyoverdine I is the main siderophore secreted byPseudomonas aeruginosa PAO1 to
      obtain access to iron. After extracellular iron chelation, pyoverdine-Fe uptake
      into the bacteria involves a specific outer-membrane transporter, FpvA. Iron is
      then released in the periplasm by a mechanism involving no siderophore
      modification but probably iron reduction. The proteins involved in this
      dissociation step are currently unknown. The pyoverdine locus contains the
      fpvCDEF operon, which contains four genes. These genes encode an ABC transporter
      of unknown function with the distinguishing characteristic of encompassing two
      periplasmic binding proteins, FpvC and FpvF, associated with the ATPase, FpvE,
      and the permease, FpvD. Deletion of these four genes partially inhibited
      cytoplasmic uptake of (55)Fe in the presence of pyoverdine and markedly slowed
      down the in vivo kinetics of iron release from the siderophore. This transporter
      is therefore involved in iron acquisition by pyoverdine in P. aeruginosa.
      Sequence alignments clearly showed that FpvC and FpvF belong to two different
      subgroups of periplasmic binding proteins. FpvC appears to be a metal-binding
      protein, whereas FpvF has homology with ferrisiderophore binding proteins. In
      vivo cross-linking assays and incubation of purified FpvC and FpvF proteins
      showed formation of complexes between both proteins. These complexes were able to
      bind in vitro PVDI-Fe, PVDI-Ga, or apo PVDI. This is the first example of an ABC
      transporter involved in iron acquisition via siderophores, with two periplasmic
      binding proteins interacting with the ferrisiderophore. The possible roles of
      FpvCDEF in iron uptake by the PVDI pathway are discussed.

PMID- 23009328
TI  - Resonance in neocortical neurons and networks.
AB  - Neocortical networks produce oscillations that often correspond to characteristic
      physiological or pathological patterns. However, the mechanisms underlying the
      generation of and the transitions between such oscillatory states remain poorly
      understood. In this study, we examined resonance in mouse layer V neocortical
      pyramidal neurons. To accomplish this, we employed standard electrophysiology to
      describe cellular resonance parameters. Bode plot analysis revealed a range of
      resonance magnitude values in layer V neurons and demonstrated that both
      magnitude and phase response characteristics of layer V neocortical pyramidal
      neurons are modulated by changes in the extracellular environment. Specifically,
      increased resonant frequencies and total inductive areas were observed at higher
      extracellular potassium concentrations and more hyperpolarised membrane
      potentials. Experiments using pharmacological agents suggested that current
      through hyperpolarization-activated cyclic nucleotide-gated channels (I(h) ) acts
      as the primary driver of resonance in these neurons, with other potassium
      currents, such as A-type potassium current and delayed-rectifier potassium
      current (Kv1.4 and Kv1.1, respectively), contributing auxiliary roles. The
      persistent sodium current was also shown to play a role in amplifying the
      magnitude of resonance without contributing significantly to the phase response.
      Although resonance effects in individual neurons are small, their properties
      embedded in large networks may significantly affect network behavior and may have
      potential implications for pathological processes.

PMID- 23009329
TI  - Pex5p stabilizes Pex14p: a study using a newly isolated pex5 CHO cell mutant,
      ZPEG101.
AB  - Pex5p [PTS (peroxisome-targeting signal) type 1 receptor] plays an essential role
      in peroxisomal matrix protein import. In the present study, we isolated a novel
      PEX5-deficient CHO (Chinese-hamster ovary) cell mutant, termed ZPEG101, showing
      typical peroxisomal import defects of both PTS1 and PTS2 proteins. ZPEG101 is
      distinct from other known pex5 CHO mutants in its Pex5p expression. An
      undetectable level of Pex5p in ZPEG101 results in unstable Pex14p, which is due
      to inefficient translocation to the peroxisomal membrane. All of the mutant
      phenotypes of ZPEG101 are restored by expression of wild-type Pex5pL, a longer
      form of Pex5p, suggesting a role for Pex5p in sustaining the levels of Pex14p in
      addition to peroxisomal matrix protein import. Complementation analysis using
      various Pex5p mutants revealed that in the seven pentapeptide WXXXF/Y motifs in
      Pex5pL, known as the multiple binding sites for Pex14p, the fifth motif is an
      auxiliary binding site for Pex14p and is required for Pex14p stability.
      Furthermore, we found that Pex5p-Pex13p interaction is essential for the import
      of PTS1 proteins as well as catalase, but not for that of PTS2 proteins.
      Therefore ZPEG101 with no Pex5p would be a useful tool for investigating Pex5p
      function and delineating the mechanisms underlying peroxisomal matrix protein
      import.

PMID- 23009330
TI  - Medicare Part D and potentially inappropriate medication use in the elderly.
AB  - OBJECTIVES: Inappropriate medication use, which is common in older adults, may be
      responsive to out-of-pocket costs. We examined the impact of Medicare Part D on
      inappropriate medication use among Medicare beneficiaries. STUDY DESIGN: Pre-post
      with comparison group. METHODS: Using data from 34,679 elderly beneficiaries in
      Medicare plans from 2004 to 2007, we used Healthcare Effectiveness Data and
      Information Set measures of prescribing quality: (1) any use of Drugs to Avoid in
      the Elderly (DAE), (2) a proportion of total medication use attributable to DAEs,
      and (3) any Potentially Harmful Drug-Disease Interactions in the Elderly (DDE).
      Rates of inappropriate use among 3 groups transitioning from no drug coverage or
      limited coverage ($150 or $350 quarterly caps) to Part D in 2006 were compared
      with those with constant drug coverage. RESULTS: DAE use increased slightly among
      those moving from no coverage to Part D (from 15.72%-17.61%) whereas the
      comparison group's use decreased (20.97%-18.32%) [relative odds ratio (ROR) =
      1.34, 95% confidence interval [CI] 1.22-1.48, P <.0001]. However, the proportion
      of total drug use attributable to DAEs declined among the no coverage group after
      Part D (3.01%-1.98%), a significant difference relative to the comparison group
      (ROR = 0.84, 95% CI 0.72-0.98, P = .03). Rates of DDE were low (1%) both before
      and after Part D. CONCLUSIONS: While use of high-risk drugs increased slightly
      among those gaining Part D drug coverage, high-risk drug use actually declined as
      a proportion of total drug use, and the prevalence of drug-disease interactions
      remained stable.

PMID- 23009331
TI  - Frequency of and harm associated with primary care safety incidents.
AB  - OBJECTIVE: To assess frequency and severity of patient safety incidents in
      primary care. STUDY DESIGN: Cross-sectional survey of health-care professionals
      in Swiss primary care offices. METHODS: Physicians and nurses in primary care
      offices were surveyed about the frequency and severity of 23 safety incidents.
      Differences between professional groups and types of offices were analyzed.
      Reported incidents were classified in a matrix. RESULTS: A total of 630
      individuals (50.2% physicians, 49.8% nurses) participated. Among them, 30% of
      physicians (95% confidence interval [CI] 25%-35%) and 16.6% of nurses (95% CI 12%
      21%) reported that at least 1 of the incidents occurred daily or weekly in their
      offices (c2 16.1, P <.001). On average, each responder reported a total of 92
      incidents during the preceding 12 months (mean of 117 events for physicians, mean
      of 66 events for nurses; P <.001). Documentation failure was reported most
      frequently.The highest fraction of last occurrences with severe injury or death
      was for diagnostic errors (4.1%). Unadjusted for caseload, staff working in
      medical centers reported higher frequencies of several incidents. The frequency
      harm matrix suggests that triage by nurse at initial contact, diagnostic errors,
      medication errors, failure to monitor patients after medical procedures, and test
      or intervention errors should be prioritized for action. CONCLUSIONS: This study
      presents a supplemental approach to identification of safety threats in primary
      care. Many incidents occur regularly and are highly relevant for healthcare
      professionals' daily work.The results offer guidance on setting priorities for
      patient safety in primary care.

PMID- 23009332
TI  - Outcomes associated with timing of maintenance treatment for COPD exacerbation.
AB  - OBJECTIVES: To examine the impact of timing of maintenance treatment initiation
      (early vs delayed) on risk of future exacerbations and costs in chronic
      obstructive pulmonary disease (COPD) patients. STUDY DESIGN: Retrospective cohort
      design using data (January 1, 2003, through June 30, 2009) from a large, US-based
      integrated pharmacy and medical claims database. METHODS: Administrative claims
      from January 1, 2003, through June 30, 2009, were used. Methotrexate (MTx)-naive
      patients (aged >40 years) with at least 1 COPD-related hospitalization/emergency
      department (ED) visit were included (discharge date was index date). Patients
      initiating MTx within the first 30 days and 31 to 180 days post-index were
      classified into early and delayed cohorts, respectively. Clinical and economic
      outcomes related to COPD exacerbations were assessed for 1 year post-index and
      compared between cohorts using regression models controlling for baseline
      characteristics. The incremental effect on outcomes of every 30-day delay in MTx
      initiation up to 6 months after the index event was also assessed. RESULTS: The
      majority of the 3806 patients (78.6%) received early MTx. A significantly higher
      proportion of patients in the delayed cohort had a COPD-related
      hospitalization/ED visit compared with the early cohort (25.6% vs 18.0%; P
      <.001). After controlling for baseline differences, the delayed cohort had a 43%
      (P <.001) higher risk of a future COPD-related hospitalization/ED visit compared
      with the early cohort. Every 30-day delay was associated with 9% risk increase (P
      = .002). Treatment delay also increased COPD-related costs ($5012 vs $3585; P
      <.001). CONCLUSION: Early MTx initiation is associated with reduced risk of
      future COPD exacerbations and lower costs.

PMID- 23009333
TI  - Antidepressant medication adherence via interactive voice response telephone
      calls.
AB  - OBJECTIVES: Outpatients given antidepressants discontinue treatment at a high
      rate during the first few months. We evaluated the effectiveness of Highmark's
      use of interactive voice response (IVR) to improve antidepressant medication
      adherence. STUDY DESIGN: Quasi-experimental cohort intervention study. METHODS:
      We placed 39,020 members newly given antidepressant medication into 3
      intervention groups based on results of interactive voice response (IVR) call 1
      month post-prescription: (1) not reached; (2) reached but not transferred to
      depression management consultant (DMC); and (3) reached and transferred to DMC.
      We evaluated medication adherence based on the Healthcare Effectiveness Data and
      Information Set effective acute phase (3 months) and continuation phase (6
      months) treatment outcomes using member claims data. We used generalized
      estimating equations to model intervention effectiveness on medication adherence.
      RESULTS: Adherence increased markedly with age group, with members older than 65
      years having a 5.11-fold higher odds (P <.0001) of compliance than the baseline
      group aged 18 to 24 years. In models adjusted for time, month of intervention,
      and drug, the odds of compliance for groups (3) and (2) relative to group (1)
      were 1.34 (P = .009) and 1.19 (P <.001), respectively. In models also adjusted
      for age group, the group (3) and (2) odds decreased to 1.00 and 1.03 and were not
      statistically significant. CONCLUSIONS: We found that IVR calls had little impact
      on antidepressant medication adherence rates. Adherence rates increased markedly
      with increasing age in each intervention group, suggesting that other
      intervention strategies to improve adherence should focus on the younger segment
      of the patient population.

PMID- 23009334
TI  - Measuring value for low-acuity care across settings.
AB  - Increasing healthcare costs have created an emphasis on improving value, defined
      as how invested time, money, and resources improve health. The role of emergency
      departments (EDs) within value-driven health systems is still undetermined. Often
      questioned is the value of an ED visit for conditions that could be reasonably
      treated elsewhere such as office-based, urgent, and retail clinics. This paper
      presents a conceptual approach to assess the value of these low-acuity visits. It
      adapts an existing analytic model to highlight specific factors that impact key
      stakeholders' (patients, insurers, and society) assessments of the value of ED
      based care compared with care in alternative settings. These factors are
      presented in 3 equations, 1 for each stakeholder, emphasizing how tangible and
      intangible benefits of care weigh against direct and indirect costs and how each
      perspective influences value. Aligning value among groups could allow
      stakeholders to influence each other and could guide rational change in the
      delivery of acute medical care for low-acuity conditions.

PMID- 23009335
TI  - Restraint use in acute and extended mental health services for older persons.
AB  - Restraint of older persons in inpatient and residential care is used to control
      aggression, and prevent falls and other adverse outcomes. Initiatives to reduce
      these practices are being implemented worldwide. However, there has been little
      examination of restraint practice in psychiatric services for older persons. This
      paper reports a retrospective comparative analysis of restraint use in three
      acute and two extended care psychiatric inpatient wards in Australia. The
      analysis involved examination of restraint incidents and comparison of restrained
      and non-restrained patients. There was significant variation in restraint use
      between wards. On one acute ward, 12.74% of patients were restrained, although
      restraint use declined during the data collection period. Patients with dementia
      were restrained at higher rates than patients with other diagnoses, and
      restrained patients stayed in hospital for a longer duration. Restraint occurred
      early in admission, and few differences emerged between those restrained once or
      multiple times. Mechanical restraint was more prevalent than physical restraint,
      with restraint predominantly used to manage aggression and falls. Findings
      provide new data on restraint in older persons' psychiatric services. Greater
      conceptual understandings of behaviours associated with dementia and the unique
      needs of patients with these disorders may assist in reducing restraint use in
      these settings. 

PMID- 23009336
TI  - EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like
      side-population cells in non-small cell lung cancer.
AB  - BACKGROUND: Cancer stem cells are thought to be responsible for the initiation
      and progression of cancers. In non-small cell lung cancers (NSCLCs), Hoechst
      33342 dye effluxing side population (SP) cells are shown to have stem cell like
      properties. The oncogenic capacity of cancer stem-like cells is in part due to
      their ability to self-renew; however the mechanistic correlation between
      oncogenic pathways and self-renewal of cancer stem-like cells has remained
      elusive. Here we characterized the SP cells at the molecular level and evaluated
      its ability to generate tumors at the orthotopic site in the lung
      microenvironment. Further, we investigated if the self-renewal of SP cells is
      dependent on EGFR mediated signaling. RESULTS: SP cells were detected and
      isolated from multiple NSCLC cell lines (H1650, H1975, A549), as well as primary
      human tumor explants grown in nude mice. SP cells demonstrated stem-like
      properties including ability to self-renew and grow as spheres; they were able to
      generate primary and metastatic tumors upon orthotopic implantation into the lung
      of SCID mice. In vitro study revealed elevated expression of stem cell associated
      markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to
      mesenchymal transition features in SP cells. Further, we show that abrogation of
      EGFR, Src and Akt signaling through pharmacological or genetic inhibitors
      suppresses the self-renewal growth and expansion of SP-cells and resulted in
      specific downregulation of Sox2 protein expression. siRNA mediated depletion of
      Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity;
      whereas other transcription factors like Oct4 and Nanog played a relatively
      lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in
      metastatic foci of human NSCLC samples. CONCLUSIONS: Our findings suggest that
      Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self
      renewal and expansion of stem-like cells from NSCLC. Therefore, the outcome of
      the EGFR-Src-Akt targeted therapy may rely upon the expression and function of
      Sox2 within the NSCLC-CSCs.

PMID- 23009338
TI  - Age-related associative deficits and the isolation effect.
AB  - If all but one of the items in a list are similar (e.g., all black except one
      red), memory for the different item is enhanced (the isolation effect). Older
      adults generally show similar or smaller isolation effects compared to young
      adults, which has been attributed to age-related deficits in associative memory
      whereby older adults are less able to associate an isolated stimulus to its
      isolating feature. Experiment 1 examined the isolation effect for isolation based
      on spatial position, modality and color; in Experiment 2, the criterion for
      isolation was the associative relation between stimuli. The results consistently
      showed no differences between young and older participants in the magnitude of
      the isolation effect. Whilst age deficits in associative memory may act to reduce
      the isolation effect in older adults, age deficits in self-initiated processing
      and inhibitory functionality may counteract this reduction by enhancing the
      isolation effect in older adults. 

PMID- 23009339
TI  - pH and solvent H/D isotope effects on the thermodynamics and kinetics of electron
      transfer for electrode-immobilized native and urea-unfolded stellacyanin.
AB  - The thermodynamics of Cu(II) to Cu(I) reduction and the kinetics of the electron
      transfer (ET) process for  Rhus vernicifera  stellacyanin (STC) immobilized on a
      decane-1-thiol coated gold electrode have been measured through cyclic
      voltammetry at varying pH and temperature, in the presence of urea and in D(2)O.
      Immobilized STC undergoes a limited conformational change that mainly results in
      an enhanced exposure of one or both copper binding histidines to solvent which
      slightly stabilizes the cupric state and increases histidine basicity. The large
      immobilization-induced increase in the pK(a) for the acid transition (from 4.5 to
      6.3) makes this electrode-SAM-protein construct an attractive candidate as a
      biomolecular ET switch operating near neutral pH in molecular electronics. Such a
      potential interest is increased by the robustness of this interface against
      chemical unfolding as it undergoes only moderate changes in the reduction
      thermodynamics and in the ET rate in the presence of up to 8 M urea. The
      sensitivity of these parameters to solvent H/D isotope effects testifies to the
      role of protein solvation as effector of the thermodynamics and kinetics of ET.

PMID- 23009340
TI  - The effects of perineural and intrasynovial anaesthesia of the equine foot on
      subsequent magnetic resonance images.
AB  - REASONS FOR PERFORMING STUDY: Artefacts caused by regional anaesthesia can
      influence image interpretation of ultrasonography and nuclear scintigraphy.
      Perineural and intrasynovial anaesthesia are commonly performed prior to magnetic
      resonance imaging (MRI); and the effects on MR images, if any, are unknown.
      OBJECTIVES: To determine if perineural and intrasynovial anaesthesia of
      structures in the equine foot cause iatrogenic changes detectable with MRI.
      METHODS: A baseline MRI examination of both front feet was performed on 15
      horses, 2-6 days prior to mepivacaine injection adjacent to the lateral and
      medial palmar digital nerves, and into the podotrochlear bursa, digital flexor
      tendon sheath and distal interphalangeal joint of one randomly assigned forelimb.
      Magnetic resonance imaging was repeated at 24 and 72 h post injection; then
      qualitative and quantitative assessments of MRI findings were performed. RESULTS:
      Magnetic resonance imaging findings associated with the palmar digital nerves,
      podotrochlear bursa and distal interphalangeal joint at 24 and 72 h after
      mepivacaine injection did not alter significantly from those at baseline.
      Compared with baseline, a significant increase in synovial fluid volume of the
      digital flexor tendon sheath was detected with MRI at 24 and 72 h post injection.
      CONCLUSIONS: Perineural anaesthesia of the palmar digital nerves and
      intrasynovial anaesthesia of the podotrochlear or distal interphalangeal joint
      did not interfere with the interpretation of MR images acquired at 24 or 72 h
      after injection. However, intrasynovial anaesthesia of the digital flexor tendon
      sheath caused an iatrogenic increase in synovial fluid, detectable on MR images
      for at least 72 h. POTENTIAL RELEVANCE: Although a definite time frame for
      resolution of digital flexor tendon sheath distension was not determined, we
      recommend waiting more than 3 days between intrasynovial anaesthesia of the
      digital flexor tendon sheath and evaluation with MRI.

PMID- 23009341
TI  - Cardiac damage induced by immunization with heat-killed Trypanosoma cruzi is not
      antibody mediated.
AB  - Cardiac inflammation that develops during infection with Trypanosoma cruzi may
      result in part from autoimmunity, which may occur after bystander activation,
      after parasite-induced cardiomyocyte damage, or molecular mimicry. A/J mice
      infected with T. cruzi or immunized with heat-killed T. cruzi (HKTC) develop
      strong autoimmunity accompanied by cardiac damage. To determine whether this
      cardiac damage occurs via an antibody-dependent mechanism, we analysed T. cruzi
      infected and HKTC-immunized mice for the presence of autoantibodies, cardiac
      antibody deposition, and serum cardiac troponin I as a measure of cardiac damage.
      We also performed a serum transfer experiment in which sera from T. cruzi
      infected and T. cruzi-immunized mice (and controls) were transferred into naive
      recipients, which were then analysed for the presence of antibodies and serum
      troponin. Unlike T. cruzi-infected mice, T. cruzi-immunized mice did not show
      significant antibody deposition in the myocardium. These results indicate that
      antibody deposition does not precede cardiac damage and inflammation in mice
      immunized with or infected with T. cruzi. Serum adoptive transfer did not induce
      cardiac damage in any recipients. Based on these findings, we conclude that the
      cardiac damage induced by immunization with HKTC is not mediated by antibodies.

PMID- 23009337
TI  - Biological rationale for the design of polymeric anti-cancer nanomedicines.
AB  - Understanding the biological features of cancer is the basis for designing
      efficient anti-cancer nanomedicines. On one hand, important therapeutic targets
      for anti-cancer nanomedicines need to be identified based on cancer biology, to
      address the unmet medical needs. On the other hand, the unique pathophysiological
      properties of cancer affect the delivery and interactions of anti-cancer
      nanomedicines with their therapeutic targets. This review discusses several
      critical cancer biological properties that challenge the currently available anti
      cancer treatments, including cancer heterogeneity and cancer stem cells, the
      complexcity of tumor microenvironment, and the inevitable cancer metastases. In
      addition, the biological bases of the enhanced permeability and retention (EPR)
      effect and tumor-specific active targeting, as well as the physiological barriers
      for passive and active targeting of anti-cancer nanomedicines are covered in this
      review. Correspondingly, possible nanomedicine strategies to target cancer
      heterogeneity, cancer stem cells and metastases, to overcome the challenges
      related to tumor passive targeting and tumor penetration, and to improve the
      interactions of therapeutic payloads with the therapeutic targets are discussed.
      The focus is mainly on the designs of polymeric anti-cancer nanomedicines.

PMID- 23009342
TI  - Evaluation of Coxiella burnetii status in dairy cattle herds with bulk-tank milk
      positive by ELISA and PCR.
AB  - Bulk-tank milk (BTM) samples are frequently used to evaluate the health status of
      dairy livestock. A large-scale investigation carried out in BTM samples from
      dairy cattle herds from a Q fever-endemic region in Northern Spain revealed a
      high degree of exposure to Coxiella burnetii. This study was aimed at assessing
      the value of BTM samples analysis as an indicator of the C. burnetii status in
      dairy cattle herds. Three herds with BTM samples positive for C. burnetii by
      ELISA and PCR were selected, and blood, faeces and individual milk and BTM
      samples were analysed by serology and PCR. In spite of the high antibodies titres
      found in BTM samples, only one of the three farms presented an active infection
      by C. burnetii, as revealed by the presence of bacterial DNA in vaginal mucus and
      in environmental samples collected in the calving area, a seroprevalence around
      40% in heifers and the seroconversion rate observed in cows. Results obtained
      indicated that the analysis of BTM samples is a good epidemiological tool at the
      population level that can be used to discriminate between seropositive and
      seronegative herds, but at the herd level, additional tests are necessary to
      evaluate whether Q fever is a potential problem in the farm. When Q fever is
      suspected in a cattle herd, sera from a small group of 1- to 3-year-old animals
      need to be analysed to investigate recent contact with C. burnetii. 

PMID- 23009343
TI  - Performance comparison of phenotypic and molecular methods for detection and
      differentiation of Candida albicans and Candida dubliniensis.
AB  - BACKGROUND: Candida albicans is the most pathogenic Candida species but shares
      many phenotypic features with Candida dubliniensis and may, therefore, be
      misidentified in clinical microbiology laboratories. Candidemia cases due to C.
      dubliniensis are increasingly being reported in recent years. Accurate
      identification is warranted since mortality rates are highest for C. albicans
      infections, however, C. dubliniensis has the propensity to develop resistance
      against azoles more easily. We developed a duplex PCR assay for rapid detection
      and differentiation of C. albicans from C. dubliniensis for resource-poor
      settings equipped with basic PCR technology and compared its performance with
      three phenotypic methods. METHODS: Duplex PCR was performed on 122 germ tube
      positive and 12 germ tube negative isolates of Candida species previously
      identified by assimilation profiles on Vitek 2 ID-YST system. Typical morphologic
      characteristics on simplified sunflower seed agar (SSA), and reaction with a
      commercial (Bichro-Dubli) latex agglutination test were also performed. The assay
      was further applied on 239 clinical yeast and yeast-like fungi and results were
      confirmed by DNA sequencing of internal transcribed spacer (ITS) region of rDNA.
      RESULTS: The results of duplex PCR assay for 122 germ tube positive and 12 germ
      tube negative isolates of Candida species were comparable to their identification
      by Vitek 2 ID-YST system, colony characteristics on SSA and latex agglutination
      test. Application of duplex PCR also correctly identified all 148 C. albicans and
      50 C. dubliniensis strains among 239 yeast-like fungi. CONCLUSIONS: The data show
      that both, duplex PCR and Bichro-Dubli are reliable tests for rapid (within few
      hours) identification of clinical yeast isolates as C. dubliniensis or C.
      albicans. However, duplex PCR may be applied directly on clinical yeast isolates
      for their identification as C. dubliniensis or C. albicans as it does not require
      prior testing for germ tube formation or latex Candida agglutination.

PMID- 23009344
TI  - Synergism of clinical evaluation and penile sonographic imaging in diagnosis of
      penile fracture: a case report.
AB  - INTRODUCTION: Penile fracture is an uncommon urologic emergency, and is the
      traumatic rupture of the tunica albuginea covering the corpus cavernosa. This
      usually occurs following blunt trauma sustained during coitus, masturbation or
      self-manipulations to hide or suppress an erection. Clinical diagnosis can often
      be easily made with typical history and examination findings. However, the
      patient may present atypically and/or with a suspicion of associated urethral
      injury. The roles of various diagnostic investigations are being evaluated in
      these situations. CASE PRESENTATION: We report the case of a 31-year-old African
      man with penile fracture and suspected associated urethral injury that occurred
      after self-manipulations to hide an erection. CONCLUSIONS: Penile ultrasound and
      sonourethrography provide useful additional diagnostic information to supplement
      clinical history and physical examination findings and can be performed easily,
      at low cost and with no delays to surgery.

PMID- 23009345
TI  - Dissociation of molecular iodine in a flow tube in the presence of O2(1Sigma)
      molecules.
AB  - Molecular iodine dissociates in the presence of O(2)((1)Delta) and O(2)((1)Sigma)
      molecules, but the mechanism of this process is not completely understood. In
      this paper, using flow tube experiments, we  studied the initiation stage of 
      iodine dissociation. Absolute spectral irradiance measurements were employed for
      measurements of concentrations of electronically excited particles. It was found
      that under the present experimental conditions  initiation of  iodine
      dissociation is mainly caused by reaction O(2)((1)Sigma) + I(2) -> O(2)((3)Sigma)
      + 2I with a rate constant of (9.3 +/- 2.0) * 10(-11) cm(3) s(-1). An appreciable
      role of the O(2)((1)Delta) molecule as the dissociation initiator has not been
      observed. It was observed that the growth rate of iodine atoms sharply
      accelerated when the concentration of I((2)P(1/2)) atoms approached 2 * 10(-4) of
      O(2)((1)Delta) concentration or when production rates of O(2)((1)Sigma) molecules
      in reactions O(2)((1)Delta) + I((2)P(1/2)) and O(2)((1)Delta) + O(2)((1)Delta)
      became equal.

PMID- 23009346
TI  - The other side of rumination: reflective pondering as a strategy for regulating
      emotions in social situations.
AB  - Recent studies have questioned the idea of rumination as a unitary dysfunctional
      process and identified an adaptive subcomponent: reflective pondering. We tested
      whether reflective pondering could represent an adaptive strategy of regulating
      emotions, and contrasted it with reappraisal and acceptance, strategies linked to
      major psychotherapeutic approaches. Participants (103 students) received training
      in one of these and were exposed to a negative mood induction consisting of
      social scenarios, both in the presence and in the absence of the specific emotion
      regulation instruction. Acceptance was more useful than reflective pondering in
      impacting negative emotions and anxiety. Reappraisal was more efficient than
      pondering for anxiety. However, moderation analysis showed that social anxiety
      (SA) levels influenced the comparative efficiency of reappraisal and acceptance
      as contrasted to reflective pondering for negative emotions and anxiety.
      Participants low in SA made equal use of all strategies, while for those high in
      SA reappraisal and acceptance were more efficient than pondering. Our results
      provide preliminary evidence that reflective pondering can, in some
      circumstances, be an adaptive regulation strategy. 

PMID- 23009347
TI  - The impact of outmigration of men on fertility and marriage in the migrant
      sending states of Mexico, 1995-2000.
AB  - Using the 2000 Mexican Census, we examined whether the level of migration was
      associated with total fertility and the proportion of women married in 314
      municipalities from seven traditional sending states. Across these
      municipalities, we observe lower fertility in higher-migration areas.
      Municipalities in the quartile with the highest levels of migration have total
      fertility more than half a child lower than municipalities in the lowest
      migration quartile. However, there are no differences in marital fertility by
      level of migration, indicating that lower proportions of women married account
      for lower total fertility in high-migration municipalities. In municipal-level
      regression models, lower sex ratios are associated with a lower proportion of
      women married, while there is an inverse association between education and
      marriage. The level of migration also has an independent association with
      marriage, suggesting that there may be changing ideas surrounding family
      formation in high-migration areas.

PMID- 23009348
TI  - Flexible bronchoscopy may decrease respiratory muscle strength: premedicational
      midazolam in focus.
AB  - BACKGROUND: Flexible bronchoscopy (FB) is a procedure accepted to be safe in
      general, with low complication rates reported. On the other hand, it is known
      that patients with pre-existing respiratory failure have developed
      hypoventilation following FB. In this study the effects of FB on respiratory
      muscle strength were investigated by measuring maximum respiratory pressures.
      METHODS: One hundred and forty patients, aged between 25 and 90 years, who had
      undergone diagnostic bronchoscopy between February 2012 and May 2012, were
      recruited to the study. Pre- and post-procedure maximal inspiratory pressure
      (MIP) and maximal expiratory pressure (MEP) were measured. A correlation between
      the MIP and MEP changes and patient characteristics and FB variables were
      investigated. RESULTS: Significant decreases in both MIP and MEP values were
      observed following FB (p < 0.001 for both). Decreases were attributed to the
      midazolam used for sedation. Significant decreases in respiratory muscle
      strengths were observed especially in the high-dose midazolam group, compared to
      both low-dose and non-midazolam groups. CONCLUSIONS: It was determined that
      respiratory muscle weakness may arise post-procedure in patients who have
      undergone FB, and this is constitutively related to midazolam premedication.
      Respiratory muscle weakness might play a role in potential hypoventilation in
      critical patients who undergo FB.

PMID- 23009349
TI  - Development of an improved polykaryon-based influenza virus rescue system.
AB  - BACKGROUND: Virus rescue from transfected cells is an extremely useful technique
      that allows defined viral clones to be engineered for the purpose of rational
      vaccine design or fundamental reverse genetics studies. However, it is often
      hindered by low primary rescue success rates or yields, especially with field
      derived viral strains. APPROACH: We investigated the possibility of enhancing
      influenza virus rescue by eliciting cell fusion to increase the chances of having
      all necessary plasmids expressed within the same polykaryon. To this end we used
      the Maedi-Visna Virus envelope protein which has potent fusion activity in cells
      from a wide range of different species. RESULTS: Co-transfecting cells with the
      eight plasmids necessary to rescue influenza virus plus a plasmid expressing the
      Maedi-Visna Virus envelope protein resulted in increased rescue efficiency. In
      addition, partial complements of the 8-plasmid rescue system could be transfected
      into two separate populations of cells, which upon fusion led to live virus
      rescue. CONCLUSION: The simple modification described here has the potential to
      improve the efficiency of the virus rescue process and expand the potential
      applications for reverse genetic studies.

PMID- 23009350
TI  - Regional dissemination of Acinetobacter species harbouring metallo-beta-lactamase
      genes in Japan.
AB  - Metallo-beta-lactamase (MBL) producers have been reported among the various
      Acinetobacter species worldwide. In this study, the epidemiology and molecular
      characteristics of carbapenemase-encoding genes and mobile elements were studied
      to analyse the regional dissemination of MBL genes in Acinetobacter species. From
      January 2001 to December 2006, 48 Acinetobacter isolates harbouring MBL genes
      identified from five hospitals in Kyoto and Shiga Prefecture, Japan were
      collected and analysed. The partial rpoB gene or the 16S-23S ribosomal RNA
      intergenic spacer region was sequenced to obtain a species-level identification.
      Molecular typing using pulsed-field gel electrophoresis (PFGE) and multilocus
      sequence typing (MLST) was performed. Twenty-five Acinetobacter pittii isolates
      were divided into eight PFGE types and five sequence types (STs) using MLST. Nine
      Acinetobacter bereziniae isolates belonged to five PFGE types. Five Acinetobacter
      nosocomialis isolates were divided into two PFGE types and two STs. Three
      unclassified Acinetobacter species isolates were divided into two PFGE types.
      Eighteen of the 25 A. pittii isolates belonged to ST119 and were identified from
      four hospitals. The bla(IMP-19) gene was detected in 41 of 48 isolates, including
      all of the A. pittii ST119 isolates. The bla(IMP-1) and bla(IMP-11) genes were
      detected in four and three isolates, respectively. The MBL genes were all
      embedded within a class 1 integron as a gene cassette array: bla(IMP-19) -aac(6')
      31-bla(OXA-21) -aadA1, catB8-like/aacA4-bla(IMP-1) and bla(IMP-11). This study is
      the first report demonstrating the regional dissemination of MBL-producing
      Acinetobacter species. A. pittii ST119 harbouring blaIMP-19 was widely spread
      throughout the Kyoto-Shiga region.

PMID- 23009351
TI  - pH-and thermo-sensitive pluronic/poly(acrylic acid) in situ hydrogels for
      sustained release of an anticancer drug.
AB  - In this study, we developed oral in situ gelling formulations composed of
      pluronic (Plu) and polyacrylic acid (PAA) for the delivery of an anticancer drug,
      epirubicin (Epi). We investigated various Plu/PAA/Epi formulations for their
      physicochemical properties and in vitro permeation and accumulation, as well as
      for in vivo pharmacokinetic and antitumor efficacy. A scanning electron
      microscopic (SEM) image of Plu 14%/PAA 0.75%/Epi hydrogel showed a sponge-like
      structure. This formulation has suitable gelation time, water content,
      bioadhesive force, structural stability, and a high permeation percentage of Epi,
      with sustained drug release characteristics for 96 h. This hydrogel was retained
      at the end of the ileum near the colon of Sprague-Dawley (SD) rats for at least
      12 h. An in vivo pharmacokinetic study using SD rats showed that after oral
      administration in this formulation, Epi had prolonged half-life, greater area
      under the curve, and higher relative bioavailability than in an oral Epi
      solution. In vivo tumor growth inhibition of Epi in this formulation was more
      pronounced compared with oral Epi and intravenous Epi solutions in CT-26 mouse
      colon adenocarcinoma bearing Balb/c mice. This study highlights the advantages of
      using oral in situ temperature- and pH-sensitive hydrogels for future cancer
      therapy.

PMID- 23009352
TI  - Invasive duct carcinoma of the breast with multinucleated osteoclast-like giant
      cells: a rare case diagnosed on fine needle aspiration cytology.

PMID- 23009353
TI  - Limited response to CRH stimulation tests at 2 weeks of age in preterm infants
      born at less than 30 weeks of gestational age.
AB  - BACKGROUND: The high incidence of glucocorticoid-responsive complications in
      extremely preterm infants suggests the immaturity of their adrenal function;
      however, knowledge of the hypothalamus-pituitary-adrenal (HPA) axis in extremely
      preterm infants is limited. METHODS: To clarify the characteristics of the HPA
      axis in preterm very low birthweight (VLBW) infants, we performed CRH tests
      repeatedly: at about 2 weeks of age and at term (37-41 weeks of postmenstrual
      age) for 21 VLBW infants with a gestational age (GA) <30 weeks at birth. RESULTS:
      Basal cortisol values at 2 weeks of age were significantly higher than those at
      term in VLBW infants < 30 weeks of gestation at birth (304.1 +/- 146.3 nmol/l vs
      184.7 +/- 108.2 nmol/l). Response to corticotropin-releasing hormone (CRH)
      stimulation tests at 2 weeks of age was significantly lower than at term (delta
      cortisol 148.3 +/- 90.7 nmol/l vs 271.8 +/- 167.0 nmol/l, delta ACTH 3.9 +/- 3.2
      pmol/l vs 12.3 +/- 9.2 pmol/l, respectively). We found that earlier GA
      contributed to the higher basal cortisol values, and antenatal glucocorticoid
      (AG) contributed to the lower response of cortisol to CRH tests at 2 weeks of
      age. CONCLUSIONS: VLBW infants showed a characteristic pattern in the HPA axis at
      2 weeks of age: higher basal cortisol values and lower response to CRH tests.
      This study suggested that AG was related to the lower response to CRH tests, at
      least partly.

PMID- 23009354
TI  - Novel protease inhibitors via computational redesign of subtilisin BPN'
      propeptide.
AB  - The propeptide domain of subtilisin BPN' functions as a molecular chaperone for
      its cognate protease yet quickly assumes a predominantly unfolded structure
      following cleavage by the mature protease. In contrast, structural stabilization
      of the propeptide domain has been proposed to competitively inhibit protease self
      cleavage, suggesting the possibility for the generation of novel proteinaceous
      subtilisin inhibitors. Using a Rosetta fixed backbone design, we have redesigned
      the subtilisin BPN' propeptide structure to generate synthetic peptide sequences
      with increased and tunable structural stability. Molecular dynamics simulations
      provide supporting evidence that the artificial sequences retain structure
      without its protease cognate unlike the inherently disordered wild-type
      propeptide. Experimental evaluation of two designer domains by spectroscopic
      methods verified their structural integrity. Furthermore, the novel propeptide
      domains were shown to possess significantly enhanced thermostability.
      Nevertheless, their modest functional performance as protease inhibitors raises
      doubt that propeptide stability alone is sufficient for effective inhibitor
      design.

PMID- 23009355
TI  - Photoinduced dynamics of formic acid monomers and dimers: the role of the double
      hydrogen bond.
AB  - Nonadiabatic dynamics in the framework of time-dependent density functional
      theory was used to simulate gas-phase relaxation dynamics of pairs of
      conformations of formic acid monomers (cis and trans FAM) and dimers (acyclic
      aFAD and cyclic cFAD). In the early phase of the excited state dynamics,
      elongation of the C?O bond and pyramidalization of the carbon atom is observed in
      both FAM and FAD. Subsequently, the photodynamics of FAM is shown to be dominated
      by fragmentation processes occurring mostly in the excited state and resulting in
      HCO and OH radicals. In only a few cases does the dissociation take place from
      the vibrationally excited ground electronic state, whereby CO and H(2)O are the
      major reaction products. In the dimers, single proton transfer triggers ultrafast
      relaxation to the ground electronic state. In the single hydrogen bonded dimer
      about half of the trajectories dissociate into electronically excited monomers,
      whereas this potentially destructive dissociation is effectively suppressed in
      the double hydrogen bonded dimer. Upon relaxation to the ground electronic state,
      separation of FAD into monomers takes place, but without their further
      fragmentation on the time scale of the simulation. We conclude that the crucial
      difference between the FAM and FAD photodynamics is that the latter is dominated
      by nondestructive radiationless deactivation pathways during which a key
      protective role is assumed by the single (aFAD) or double (cFAD) intermonomer
      hydrogen bonds.

PMID- 23009356
TI  - Antigenic differences between the EG95-related proteins from Echinococcus
      granulosus G1 and G6 genotypes: implications for vaccination.
AB  - Cystic echinococcosis caused by Echinococcus granulosus remains an important and
      neglected issue in public health. The study of the likely efficacy of the
      currently available EG95 vaccine against other genotypes of the parasite is
      important to improve the vaccine as a potential tool to be used in control
      programmes. The recombinant vaccine EG95-1G1 was developed based on the G1
      genotype of E. granulosus. Characterization of the eg95 gene family in the G6
      genotype by genomic DNA cloning previously produced the first unequivocal
      information about the composition of the gene family in a different genotype. The
      information was used in this study to predict and express two EG95-related
      proteins from the G6 genotype as recombinants, for assessment of their capacity
      to bind antibodies raised in sheep vaccinated with the EG95-1G1 vaccine. The
      proteins (EG95-1G6 and EG95-5G6) from the G6 genotype of E. granulosus were
      unable to bind all the antibodies raised by sheep vaccinated with EG95-1G1.
      Differences in the amino acid sequence of EG95-related proteins from G6 and
      likely the differences in the encoded FnIII domain may be responsible for changes
      in the conformation of these epitopes.

PMID- 23009357
TI  - Engineering of acetyl-CoA metabolism for the improved production of
      polyhydroxybutyrate in Saccharomyces cerevisiae.
AB  - Through metabolic engineering microorganisms can be engineered to produce new
      products and further produce these with higher yield and productivities. Here, we
      expressed the bacterial polyhydroxybutyrate (PHB) pathway in the yeast
      Saccharomyces cerevisiae and we further evaluated the effect of engineering the
      formation of acetyl coenzyme A (acetyl-CoA), an intermediate of the central
      carbon metabolism and precursor of the PHB pathway, on heterologous PHB
      production by yeast. We engineered the acetyl-CoA metabolism by co-transformation
      of a plasmid containing genes for native S. cerevisiae alcohol dehydrogenase
      (ADH2), acetaldehyde dehydrogenase (ALD6), acetyl-CoA acetyltransferase (ERG10)
      and a Salmonella enterica acetyl-CoA synthetase variant (acsL641P), resulting in
      acetoacetyl-CoA overproduction, together with a plasmid containing the PHB
      pathway genes coding for acetyl-CoA acetyltransferase (phaA), NADPH-linked
      acetoacetyl-CoA reductase (phaB) and poly(3-hydroxybutyrate) polymerase (phaC)
      from Ralstonia eutropha H16. Introduction of the acetyl-CoA plasmid together with
      the PHB plasmid, improved the productivity of PHB more than 16 times compared to
      the reference strain used in this study, as well as it reduced the specific
      product formation of side products.

PMID- 23009358
TI  - The inpatient psychiatric unit as both a safe and unsafe place: implications for
      absconding.
AB  - Absconding from acute psychiatric inpatient units is a significant issue with
      serious social, economic, and emotional costs. A qualitative study was undertaken
      to explore the experiences of people (n = 12) who had been held involuntarily
      under the local mental health act in an Australian inpatient psychiatric unit,
      and who had absconded (or attempted to abscond) during this time. The aim of the
      study was to explore why people abscond from psychiatric inpatient units, drawing
      on published work from health geography on the significance of the person-place
      encounter, and in particular the concept of 'therapeutic landscapes'. The
      findings show that the inpatient unit is perceived as a safe or unsafe place,
      dependent on the dialectical relationship between the physical, individual,
      social, and symbolic aspects of the unit. Consumers absconded when the unit was
      perceived as unsafe. Forming a therapeutic relationship with staff, familiarity
      with the unit, a comfortable environment, and positive experiences with other
      consumers all supported perceptions that the unit was safe, decreasing the
      likelihood of absconding. Findings extend existing work on the person-place
      encounter within psychiatric inpatient units, and bring new knowledge about the
      reasons why consumers abscond. Implications for practice are discussed.

PMID- 23009359
TI  - Pulpar temperature changes during mechanical reduction of equine cheek teeth:
      comparison of different motorised dental instruments, duration of treatments and
      use of water cooling.
AB  - REASONS FOR PERFORMING STUDY: Although equine motorised dental instruments are
      widely used, there is limited information on their thermal effect on teeth. The
      recently described variation in subocclusal secondary dentine depth overlying
      individual pulp horns may affect heat transmission to the underlying pulps.
      OBJECTIVES: This study compared the effect of 3 different equine motorised dental
      instruments on the pulpar temperature of equine cheek teeth with and without the
      use of water cooling. It also evaluated the effect of subocclusal secondary
      dentine thickness on pulpar temperature changes. METHODS: A thermocouple probe
      was inserted into the pulp horns of 188 transversely sectioned maxillary cheek
      teeth with its tip lying subocclusally. Pulpar temperature changes were recorded
      during and following the continuous use of 3 different equine motorised dental
      instruments (A, B and C) for sequential time periods, with and without the use of
      water cooling. RESULTS: Using motorised dental instrument B compared with either
      A or C increased the likelihood that the critical temperature was reached in
      pulps by 8.6 times. Compared with rasping for 30 s, rasping for 45, 60 and 90 s
      increased the likelihood that the critical temperature would be reached in pulps
      by 7.3, 8.9 and 24.7 times, respectively. Thicker subocclusal secondary dentine
      (odds ratio [OR] = 0.75/mm) and water cooling (OR = 0.14) were both protective
      against the likelihood of the pulp reaching the critical temperature.
      CONCLUSIONS: Prolonged rasping with motorised dental instruments increased the
      likelihood that a pulp would be heated above the critical temperature. Increased
      dentinal thickness and water cooling had protective roles in reducing pulpar
      heating. POTENTIAL RELEVANCE: Motorised dental instruments have the potential to
      seriously damage equine pulp if used inappropriately. Higher speed motorised
      dental instruments should be used for less time and teeth should be water cooled
      during or immediately after instrument use to reduce the risk of thermal pulpar
      damage.

PMID- 23009360
TI  - Neural stem cells engrafted in the adult brain fuse with endogenous neurons.
AB  - Neural stem cells (NSCs) have become promising tools for basic research and
      regenerative medicine. Intracerebral transplantation studies have suggested that
      these cells may be able to adopt neuronal phenotypes typical of their engraftment
      site and to establish appropriate connections in the recipient circuitries. Here,
      we examined the in vivo neurogenic competence of well-characterized NSC lines
      subjected to in vitro priming and subsequent implantation into the adult intact
      mouse brain. Upon implantation into the hippocampus and, less frequently, in the
      striatum and in the cerebral cortex, numerous green fluorescent protein (GFP)
      tagged cells acquired differentiated features indistinguishable from resident
      neurons. Upon closer examination, however, we found that this outcome resulted
      from fusion of donor cells with local neuronal elements generating long-term
      persistent GFP(+) neuronal hybrids. This fusogenic behavior of NSCs was
      unexpected and also observed in coculture with E18 hippocampal immature neural
      cells, but not with microglia or astrocytes. Similar findings were consistently
      obtained with different NSC lines, mouse recipients, and donor cell-labeling
      methods. The frequent and cell type-specific fusion of donor NSCs with host
      neurons highlights a previously underestimated biological property of the nervous
      tissue that might prove profitable for basic and therapeutically oriented
      studies.

PMID- 23009361
TI  - Computational modeling of the mechanical modulation of the growth plate by
      sustained loading.
AB  - This paper presents a computational model that describes the growth of the bone
      as a function of the proliferation and hypertrophy of chondrocytes in the growth
      plate. We have included the effects of the mechanical loads on the sizes of the
      proliferative and hypertrophic areas, the number of proliferative chondrocytes
      and the final size of the hypertrophic chondrocytes. The validation of the model
      was performed with experimental data published on other investigations about
      proximal tibia of rats, subjected to sustained axial stresses of 0.1 MPa, 0.0
      MPa, -0.1 MPa and -0.2 MPa. Growth was simulated during 23 days, obtaining
      numerical errors between 2.77% and 3.73% with respect to experimental growth
      rates. The results obtained show that the model adequately simulates the behavior
      of the growth plate and the effect of mechanical loads over its cellular
      activity.

PMID- 23009362
TI  - Temporal features of human tendon vibration illusions.
AB  - Muscle spindles provide information about the position and movement of our
      bodies. One method for investigating spindle signals is tendon vibration.
      Vibration of flexor tendons can produce illusions of extension, and vibration of
      extensor tendons can produce illusions of flexion. Here we estimate the temporal
      resolution and persistence of these illusions. In Experiments 1 and 2, sequences
      of alternating vibration of wrist flexor and extensor tendons produced position
      illusions that varied with alternation period. When vibrations alternated at 1 Hz
      or slower, perceived position at the end of the sequence depended on the last
      vibration. When vibrations alternated every 0.3 s, perceived position was
      independent of the last vibration. Experiment 2 verified and extended these
      results using more trials and concurrent electromyographic recording. Although
      tendon vibrations sometimes induce reflexive muscle activity, we found no
      evidence that such activity contributed to these effects. Experiment 3
      investigated how long position sense is retained when not updated by current
      information from spindles. Our first experiments suggested that vibrating
      antagonistic tendons simultaneously could produce conflicting inputs, leaving
      position sense reliant on memory of position prior to vibration onset. We
      compared variability in position sense after different durations of such double
      vibration. After 12 s of double vibration, variability across trials exceeded
      levels predicted from vibrations of flexor or extensor tendons alone. This
      suggests that position sense memory had decayed too much to substitute for the
      current conflicting sensory information. Together, our results provide novel,
      quantitative insight into the temporal properties of tendon vibration illusions.

PMID- 23009363
TI  - Parallel Markov chain Monte Carlo - bridging the gap to high-performance Bayesian
      computation in animal breeding and genetics.
AB  - BACKGROUND: Most Bayesian models for the analysis of complex traits are not
      analytically tractable and inferences are based on computationally intensive
      techniques. This is true of Bayesian models for genome-enabled selection, which
      uses whole-genome molecular data to predict the genetic merit of candidate
      animals for breeding purposes. In this regard, parallel computing can overcome
      the bottlenecks that can arise from series computing. Hence, a major goal of the
      present study is to bridge the gap to high-performance Bayesian computation in
      the context of animal breeding and genetics. RESULTS: Parallel Monte Carlo Markov
      chain algorithms and strategies are described in the context of animal breeding
      and genetics. Parallel Monte Carlo algorithms are introduced as a starting point
      including their applications to computing single-parameter and certain multiple
      parameter models. Then, two basic approaches for parallel Markov chain Monte
      Carlo are described: one aims at parallelization within a single chain; the other
      is based on running multiple chains, yet some variants are discussed as well.
      Features and strategies of the parallel Markov chain Monte Carlo are illustrated
      using real data, including a large beef cattle dataset with 50K SNP genotypes.
      CONCLUSIONS: Parallel Markov chain Monte Carlo algorithms are useful for
      computing complex Bayesian models, which does not only lead to a dramatic speedup
      in computing but can also be used to optimize model parameters in complex
      Bayesian models. Hence, we anticipate that use of parallel Markov chain Monte
      Carlo will have a profound impact on revolutionizing the computational tools for
      genomic selection programs.

PMID- 23009365
TI  - Primary human hepatocytes versus hepatic cell line: assessing their suitability
      for in vitro nanotoxicology.
AB  - The use of hepatocyte cell lines as a replacement for animal models have been
      heavily criticised mainly due to low expression of metabolism enzymes. This study
      compares primary human hepatocytes with the C3A cell line and with respect to
      their response to a panel of nanomaterials (NMs; two ZnO, two MWCNTs, one Ag and
      one positively functionalised TiO2). The cell line was very comparable with the
      primary hepatocytes with regards to their cytotoxic response to the NMs (Ag >
      uncoated ZnO > coated ZnO). The LC50 was not attained in the presence of the
      MWCNTs and the TiO2 NMs. All NMs significantly increased IL-8 production, with no
      change in levels of TNF-alpha and IL-6. Albumin production was measured as an
      indicator of hepatic function. The authors found no change in levels of albumin
      with the exception of the coated ZnO NM at the LC50 concentration. NM uptake was
      similar for both the primary hepatocytes and C3A cells as investigated by TEM.
      Meanwhile, the authors confirmed greater levels of CYP450 activity in untreated
      primary cells. This study demonstrates that the C3A cell line is a good model for
      investigating NM-induced hepatocyte responses with respect to uptake,
      cytotoxicity, pro-inflammatory cytokine production and albumin production.

PMID- 23009364
TI  - Life satisfaction two-years after stroke onset: the effects of gender, sex
      occupational status, memory function and quality of life among stroke patients
      (Newsqol) and their family caregivers (Whoqol-bref) in Luxembourg.
AB  - BACKGROUND: Life satisfaction (LS) of cerebrovascular disease survivors and their
      family caregivers may relate to socioeconomic factors, impaired functions, health
      related quality of life (QoL), but their respective influences remain unclear.
      This study assessed, two years post-stroke onset, the effects of these factors on
      patients' LS and family caregivers' LS in Luxembourg. METHODS: All stroke
      patients admitted to all hospitals in Luxembourg were identified by the
      'Inspection General de la Securite Sociale' using the only national system
      database for care expenditure reimbursement. Their diagnosis was confirmed by
      medical investigator. The sample included ninety four patients living at home
      having given consent (mean age 65.5 years) and sixty two main caregivers (mean
      age 59.3 years). Questionnaires were completed during face-to-face interviews. LS
      was assessed via European single question (range 1-10), survivors' QoL via
      Newsqol (11 dimensions), and caregivers' QoL via Whoqol-bref (4 domains) (range 0
      100). Data were analysed using multiple regression models. RESULTS: Two years
      after stroke onset, 44.7% of patients suffered from impaired sensory function,
      35.1% from impaired motor function, and 31.9% from impaired memory function. Mean
      patient' LS was 7.1/10 (SD 1.9). It was higher in women (+12.4) and lower among
      unemployed socioeconomically active patients (-13.1, vs. retired people).
      Adjusted for sex, occupation, impaired motor and memory functions, LS positively
      correlated with scores of Newsqol feelings, sleep, emotion, cognition and pain
      dimensions (slopes 0.20 to 0.31), but did not correlate with those of caregivers'
      Whoqol-bref domains. Family caregiver' LS was 7.2 (SD 1.7). It was lower in those
      with patients suffering from impaired memory function (-12.8) as well as from
      feelings and emotion issues (slopes 0.22). It was associated with all caregivers'
      Whoqol-bref domains (physical health, psychological health, environment, and
      social relationships) (slopes 0.53 to 0.68). CONCLUSIONS: Two-year post
      cerebrovascular disease patient' LS was associated with gender, occupation, and
      impaired memory function. It correlated with feelings, sleep, emotion, cognition,
      and pain issues. Family caregivers of patients with impaired memory function had
      lower LS. Family caregiver' LS correlated with dimensions of patients' feelings
      (less independent, yourself, life changed, depressed, useless, less control
      because of stroke) and emotion (get more emotional, fear of another stroke or to
      become dependent on others), and with their own QoL. LS, Newsqol, and Whoqol
      appeared to be appropriate tools. Our findings may be useful for policy makers in
      relation to family and medical-social issues of stroke home-based rehabilitation.

PMID- 23009366
TI  - Activation of IP3 receptors requires an endogenous 1-8-14 calmodulin-binding
      motif.
AB  - Binding of IP3 (inositol 1,4,5-trisphosphate) to the IP3-binding core (residues
      224-604) of IP3Rs (IP3 receptors) initiates opening of these ubiquitous
      intracellular Ca2+ channels. The mechanisms are unresolved, but require
      conformational changes to pass through the suppressor domain (residues 1-223). A
      calmodulin-binding peptide derived from myosin light chain kinase uncouples these
      events. We identified a similar conserved 1-8-14 calmodulin-binding motif within
      the suppressor domain of IP3R1 and, using peptides and mutagenesis, we
      demonstrate that it is essential for IP3R activation, whether assessed by IP3
      evoked Ca2+ release or patch-clamp recoding of nuclear IP3R. Mimetic peptides
      specifically inhibit activation of IP3R by uncoupling the IP3-binding core from
      the suppressor domain. Mutations of key hydrophobic residues within the
      endogenous 1-8-14 motif mimic the peptides. Our results show that an endogenous 1
      8-14 motif mediates conformational changes that are essential for IP3R
      activation. The inhibitory effects of calmodulin and related proteins may result
      from disruption of this essential interaction.

PMID- 23009367
TI  - Contrasting habitat associations of imperilled endemic stream fishes from a
      global biodiversity hot spot.
AB  - BACKGROUND: Knowledge of the factors that drive species distributions provides a
      fundamental baseline for several areas of research including biogeography,
      phylogeography and biodiversity conservation. Data from 148 minimally disturbed
      sites across a large drainage system in the Cape Floristic Region of South Africa
      were used to test the hypothesis that stream fishes have similar responses to
      environmental determinants of species distribution. Two complementary statistical
      approaches, boosted regression trees and hierarchical partitioning, were used to
      model the responses of four fish species to 11 environmental predictors, and to
      quantify the independent explanatory power of each predictor. RESULTS: Elevation,
      slope, stream size, depth and water temperature were identified by both
      approaches as the most important causal factors for the spatial distribution of
      the fishes. However, the species showed marked differences in their responses to
      these environmental variables. Elevation and slope were of primary importance for
      the laterally compressed Sandelia spp. which had an upstream boundary below 430 m
      above sea level. The fusiform shaped Pseudobarbus 'Breede' was strongly
      influenced by stream width and water temperature. The small anguilliform shaped
      Galaxias 'nebula' was more sensitive to stream size and depth, and also
      penetrated into reaches at higher elevation than Sandelia spp. and Pseudobarbus
      'Breede'. CONCLUSIONS: The hypothesis that stream fishes have a common response
      to environmental descriptors is rejected. The contrasting habitat associations of
      stream fishes considered in this study could be a reflection of their
      morphological divergence which may allow them to exploit specific habitats that
      differ in their environmental stressors. Findings of this study encourage wider
      application of complementary methods in ecological studies, as they provide more
      confidence and deeper insights into the variables that should be managed to
      achieve desired conservation outcomes.

PMID- 23009368
TI  - Perceptions of stigma and barriers to care among UK military personnel deployed
      to Afghanistan and Iraq.
AB  - Perceived stigma and organizational barriers to care (stigma/BTC) can influence
      the decision to seek help for military personnel when they are suffering from
      mental health problems. We examined the relationship between stigmatizing
      beliefs, perceived BTC, and probable post-traumatic stress disorder (PTSD) in
      23,101 UK military personnel deployed to Afghanistan and Iraq both during and
      after deployment; and in a smaller group some six months later. Overall, our
      results suggest that stigma/BTC perceptions were significantly, and substantially
      higher during deployment than when personnel are returning home; however, within
      the smaller follow-up group, the rates climbed significantly over the first six
      months post-deployment although they still remained lower than during-deployment
      levels. Male personnel, those who reported higher levels of PTSD symptoms and/or
      greater combat exposure were significantly more likely to endorse more stigma/BTC
      at both sampling points. Rates of stigma/BTC on deployment are substantially
      higher than rates measured when personnel are in less threatening environments.
      We suggest that the considerable efforts that military forces make to encourage
      effective help seeking should take account of the fluctuating levels of
      stigma/BTC. Commanders should be aware that encouraging help seeking may be more
      difficult in operational environments than when personnel have returned home. 

PMID- 23009369
TI  - Metastatic pituitary carcinoma in a patient with acromegaly: a case report.
AB  - INTRODUCTION: Asymptomatic pituitary abnormalities occur in about 10% of cranial
      magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland
      is rare: 133 cases have been reported. Two thirds secreted either prolactin or
      adrenocorticotropic hormone, and another 24% were non-secreting. CASE
      PRESENTATION: A 42-year-old Caucasian man lived for 30 years after the diagnosis
      of a pituitary tumor whose clinical and biochemical features were those of
      acromegaly and hypogonadism. Radiotherapy, totaling 7300 rad, was administered to
      the sella over two courses. Growth hormone levels normalized, but he developed
      both thyroid and adrenal insufficiency, and replacement therapy was commenced.
      Fourteen years later, growth hormone levels again became elevated, and
      bromocriptine was commenced but led to side effects that could not be tolerated.
      An attempted surgical intervention failed, and octreotide and pergolide were used
      in succession. Twenty-seven years after the diagnosis, a mass from an excisional
      biopsy of below the angle of the mandible proved to be metastatic pituitary
      carcinoma. Immunohistochemical staining was positive for synaptophysin, growth
      hormone, and prolactin. One year later, an octreotide scan showed uptake at the
      sella, neck, and spleen. Our patient declined further active oncology treatment.
      CONCLUSIONS: Metastatic pituitary carcinoma associated with acromegaly is
      particularly rare. To the best of our knowledge, this is the eighth such case and
      is the first report of growth hormone and prolactin present in the metastatic
      mass.

PMID- 23009370
TI  - Loss of clinical nursing expertise: a discussion paper.
AB  - There is evidence to suggest that there is a general decline in clinical
      expertise in nursing as a result of experienced clinicians leaving the
      profession. The expertise of clinical nursing practice is an important resource
      and needs to be captured and made available to others as loss of this knowledge
      and expertise has implications for clinical outcomes. This paper aims to discuss
      the current nursing workforce, loss of clinical expertise, the nature of
      expertise and the way it can be captured. Clarification and articulation of
      clinical knowledge of nursing experts provides the means for knowledge to be
      transferred to a less experienced workforce and be available in an accessible
      form in the workplace. Leverage of nursing expertise in this manner has the
      potential to benefit less experienced staff, hold clinical nursing expertise in
      the workplace and improve clinical outcomes and satisfaction with performance.

PMID- 23009371
TI  - Integrating the online nursing evidence-based information resources for evidence
      based nursing study in China.
AB  - At present Chinese nurses could not get the up-to-date and high-quality evidences
      efficiently and conveniently due to language barrier and other practical
      difficulties. This program built a Chinese website of integrated evidence-based
      network information resources for EBN studies. Researchers hope to provide
      practical guidance and advice for nurses in non-English-speaking countries..

PMID- 23009372
TI  - Attitudes of Turkish midwives and nurses working at hospitals towards people
      living with human immunodeficiency virus/acquired immune deficiency syndrome.
AB  - Health professionals caring for people living with human immunodeficiency virus
      (HIV)/acquired immune deficiency syndrome (AIDS) show poor or negative attitudes
      because of fear of contagion. Therefore, it is important to know the attitudes of
      midwives' and nurses' towards people living with HIV/AIDS. The aim of this
      descriptive and cross-sectional study is to assess the attitudes of Turkish
      midwives and nurses working at hospitals to people living with HIV/AIDS and to
      identify factors that affect these attitudes. A group of 46 midwives and 192
      nurses working in hospitals were included in the study. Data were collected
      through AIDS Attitude Scale. Age, professional experience, number of children and
      marital status influenced the attitudes of the participants towards people living
      with HIV/AIDS. We concluded that higher level of education appear to positively
      influence the attitudes of the participants. Education programmes including
      evidence-based nursing implications might be planned to improve positive
      attitudes and to prevent stigmatization of people living with HIV/AIDS.

PMID- 23009373
TI  - The effect of individual training and counselling programme for patients with
      myocardial infarction over patients' quality of life.
AB  - The aim of the present study was to identify the effect of individual training
      and counselling programme for patients having experienced myocardial infarction
      over patients' quality of life. The sample was composed of 90 patients, 45 in the
      intervention and 45 in the control group, selected by sequential sampling from
      patients who had myocardial infarction for the first time. Data were collected
      between April and November 2008 by means of patient information form, Myocardial
      Infarction Dimensional Assessment Scale MIDAS, and Short Form SF-36. In the
      intervention group, more improvement was observed in comparison with the control
      group in terms of quitting smoking, physical activity, body mass index, waist
      circumference (mean differences P = 0.000). A significant difference was observed
      in the third month of evaluation of both MIDAS and SF-36 quality of life scales
      in comparison with the baseline values (P <= 0.000). The results indicated that
      individual training and counselling provided to patients having experienced acute
      myocardial infarction lead to improvement in quality of life and decrease risk
      factors by increasing behaviours that protect cardiac health. Such educational
      programmes should be applied to patients with acute myocardial infarction prior
      to discharge.

PMID- 23009374
TI  - Self-neglect consultation rates and comorbidities in primary care.
AB  - The aims of this study were, through secondary data analysis, to establish
      consultation rates for self-neglect by 100 000 of the Scottish population and by
      deprivation and to identify the main comorbidities associated with self-neglect.
      Data from a national dataset recording consultations in general practices where a
      self-neglect diagnoses was made were analysed. Rates of self-neglect in patients
      who consulted a Practice Nurse or General Medical Practitioners vary over time.
      Self-neglect is more common in the 75 years and over group but is found across
      the age spectrum. It is more common in males and is linked to higher levels of
      deprivation. Self-neglect is recorded as a diagnosis relatively infrequently in
      general practice. A wide range of comorbid conditions are found coexisting with
      self-neglect. Nurse interventions generally focus on comorbidities and not self
      neglect. Self-neglect does present in primary care. Nurses need to be aware of
      its varied presentations. Practice Nurse interventions suggest we need to develop
      self-management interventions rather than respond to associated comorbid
      conditions.

PMID- 23009375
TI  - Exploring the structure and organization of information within nursing clinical
      handovers.
AB  - Clinical handover is the primary source of patient information for nurses;
      however, inadequate information transfer compromises patient safety. We
      investigated the content and organization of information conveyed at 81
      handovers. A structure that captures and presents the information transferred at
      handover emerged: identification of the patient and clinical risks, clinical
      history/presentation, clinical status, care plan and outcomes/goals of care
      (ICCCO). This approach covers essential information while allowing for
      prioritization of information when required. Further research into the impact of
      ICCCO on patient safety is in progress.

PMID- 23009376
TI  - An exploratory study of complaints handling and nature.
AB  - Different countries have different complaints handling systems. This study
      reveals general pathways to handling complaints that provide an overview at the
      case hospital as well as a general complaints handling picture in Taiwan. It
      explores hospital complaints and how hospital staff handle them. A large teaching
      hospital in Taiwan was purposefully chosen as a case study. Data were collected
      through in-depth interviews, document analysis and interrogating a 3-year
      complaints archive. The study found that dissatisfaction with 'humaneness' and
      'care/treatment' commonly causes the case hospital patients to complain.
      Understanding complaint patterns, therefore, can help hospital managers improve
      organizational performance, which shows that certain service provision needs to
      be prioritized if hospital staff intend to improve service quality.

PMID- 23009377
TI  - Home environmental and health-related factors among home fallers and recurrent
      fallers in community dwelling older Korean women.
AB  - The purpose of the study was to determine home environmental and health-related
      factors among home fallers and recurrent fallers in community dwelling older
      Korean women. The study population included 438 older women aged 65 years and
      over. Measures included a checklist of home environments and health-related
      items. Risk indicators for accidental falls and recurrent falling were analysed
      using logistic regression. Logistic regression analysis revealed that chronic
      disease (odds ratio (OR) = 2.02, P = 0.007), poor night light (OR = 1.97, P =
      0.032) and obstacle of door sill (OR = 1.76, P = 0.021) were predictors of
      accidental falls, and physical inactivity (OR = 2.34, P = 0.018) and slippery
      floor in the bathroom (OR = 0.41, P = 0.034) were predictors of recurrent
      falling. The findings have implications for strategies and suggest the need to
      modify home environmental context in systematic and consistent ways and the need
      to maintain physical activities to prevent falls and recurrent falling.

PMID- 23009378
TI  - Stress and coping styles in Japanese nursing students.
AB  - The objective of this investigation was to examine the stress and coping styles
      in Japanese nursing students. The principal measures of the stress and coping
      styles were the General Health Questionnaire (GHQ)-12 and Brief Coping
      Orientations to Problems Experienced scale. In a cross-sectional analysis, 1324
      students completed the anonymous self-administered questionnaires including the
      scales earlier. Feeling stress, living with family, not eating breakfast every
      day, having no regular exercise and poor sleep were associated with GHQ responder
      (psychological distressed group). The most commonly reported source of stress was
      taking examinations, followed by relationships with friends, engaging in clinical
      practice and presenting reports. The three most common coping styles adopted by
      the nursing students were acceptance, self-distraction and using instrumental
      support. By logistic regression analysis of coping styles with GHQ responder,
      self-blame, active coping, acceptance and behavioural disengagement were highly
      associated with GHQ responder. The nursing school educators as well as students
      should be aware of stress management strategies (e.g. using active coping and
      avoiding self-blame) that may help prevent depression.

PMID- 23009379
TI  - Symptom burden: a forgotten area of measurement in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) collectively known as Crohn's disease and
      ulcerative colitis are chronic inflammatory diseases of the digestive tract.
      Periods of active and inactive disease are common along the trajectory of this
      illness. A range of symptoms such as fatigue, diarrhoea and abdominal pain are
      experienced and are often very debilitating in nature resulting in significance
      interference in daily life. Despite this, to date, research in the area of
      symptoms remains an underexplored topic. This paper aims to discuss current
      approaches to symptom assessment in IBD and the potential to measure symptom
      burden in further research, in order to gain a greater understanding into the
      experiences of individuals with IBD.

PMID- 23009380
TI  - Short hospital stays and new demands for nurse competencies.
AB  - Short hospital length of stays present new challenges for nurse competencies. The
      purpose of this study was to describe Finnish nurses' self-assessed level of
      competencies and their actual use in the ambulatory surgery setting. A cross
      sectional descriptive design was used, and the data were collected electronically
      using the Nurse Competence Scale. Statistical methods were used for analyses. The
      nurses self-assessed level of competence items ranged from moderate to excellent
      along with the increased frequency of using competencies. Statistically
      significant relationship between the level competence and age, work experience,
      work rotation and permanent position were found. The findings indicate that
      patient-centred education and ensuring of patients' well-being and safety are the
      most essential competencies in this setting. Managerial intervention can be
      focused to increase nursing competencies in these areas.

PMID- 23009381
TI  - Self-reported body weight and height on admission to hospital: a reliable method
      in multi-professional evidence-based nutritional care?
AB  - Screening patients' nutritional status on admission to hospital is recommended by
      evidence-based guidelines on malnutrition. In practice, self-reported values for
      body weight and height are often used by nurses and dieticians. This study
      assessed the accuracy of self-reported body weight and height and whether these
      self-reported values might be influenced by the nature of the health-care worker
      involved. Patients (n = 611) on admission reported their body weight and height
      to a nurse and a dietician. Reported values were analysed and compared with the
      measured values. Self-reported values for body weight and height on admission are
      not always accurate. Patients do report different values to different health-care
      workers. Self-reported values for body weight to nurses were more accurate as
      compared with dieticians. Self-reported values for body weight and height are
      subject to observer bias and should be used with caution in nutritional screening
      and multi-professional nutritional care.

PMID- 23009383
TI  - Two-center two-electron covalent bonds with deficient bonding densities.
AB  - Electron-deficient covalent bonds are a type of covalent bonds without electron
      accumulation at their bonding regions. Compared with normal covalent bonds, they
      are quite sensitive to chemical environments. Electron-deficient and normal
      covalent bonds are not isolated from each other. An electron-deficient bond may
      change to a normal one upon the change of substituting groups. Neither bond
      elongation nor atom electronegativity is directly related to the electron
      deficiency in an electron-deficient bond. Atoms in molecules (AIM) analyses
      suggest that electron-deficient bonds are characterized by positive Laplacians
      and small rho(BCP) values. The positive Laplacian is caused by insignificant
      electron accumulation perpendicular to the bond path. On the basis of electron
      localization function (ELF) descriptors, electron-deficient bonds have small
      basin populations, low eta values and high relative fluctuations. There may be
      one or two bond basins for an electron-deficient bond. In addition, such a bond
      may correlate with two more valence basins close to the two participating atoms.
      Electron-deficient bonds are usually weak and long. This is consistent with the
      low s characters in their natural bond orbitals (NBOs).

PMID- 23009382
TI  - Lymphocyte depletion in experimental hemorrhagic shock in Swine.
AB  - BACKGROUND: Hemorrhagic shock results in systemic activation of the immune
      system and leads to ischemia-reperfusion injury. Lymphocytes have been identified
      as critical mediators of the early innate immune response to ischemia-reperfusion
      injury, and immunomodulation of lymphocytes may prevent secondary immunologic
      injury in surgical and trauma patients. METHODS: Yorkshire swine were
      anesthetized and underwent a grade III liver injury with uncontrolled hemorrhage
      to induce hemorrhagic shock. Experimental groups were treated with a lymphocyte
      depletional agent, porcine polyclonal anti-thymocyte globulin (PATG) (n = 8) and
      compared to a vehicle control group (n = 9). Animals were observed over a 3 day
      survival period. Circulating lymphocytes were examined with FACS analysis for
      CD3/CD4/CD8, and central lymphocytes with mesenteric lymph node and spleen
      staining for CD3. Circulating and lung tissue16 infiltrating neutrophils were
      measured. Circulating CD3 lymphocytes in the blood and in central lymphoid organs
      (spleen/lymph node) were stained and evaluated using FACS analysis. Immune
      related gene expression from liver tissue was quantified using RT-PCR. RESULTS:
      The overall survival was 22% (2/9) in the control and 75% (6/8) in the PATG
      groups, p = 0.09; during the reperfusion period (following hemorrhage) survival
      was 25% (2/8) in the control and 100% (6/6) in the PATG groups, p = 0.008. Mean
      blood loss and hemodynamic profiles were not significantly different between the
      experimental and control groups. Circulating CD3+CD4+ lymphocytes were
      significantly depleted in the PATG group compared to control. Lymphocyte
      depletion in the setting of hemorrhagic shock also significantly decreased
      circulating and lung tissue infiltrating neutrophils, and decreased expression of
      liver ischemia gene expression. CONCLUSIONS: Lymphocyte manipulation with a
      depletional (PATG) strategy improves reperfusion survival in experimental
      hemorrhagic shock using a porcine liver injury model. This proof of principle
      study paves the way for further development of immunomodulation approaches to
      ameliorate secondary immune injury following hemorrhagic shock.

PMID- 23009384
TI  - Alveolar variant of invasive lobular carcinoma in a fibroadenoma.

PMID- 23009385
TI  - Why superhydrophobic surfaces are not always icephobic.
AB  - We discuss mechanical forces that act upon a water droplet and a piece of ice on
      a rough solid surface and the difference between dewetting and ice fracture. The
      force needed to detach a water droplet depends on contact angle (CA) hysteresis
      and can be reduced significantly in the case of a superhydrophobic surface. The
      force needed to detach a piece of ice depends on the receding CA and the initial
      size of interfacial cracks. Therefore, even surfaces with very high receding CA
      may have strong adhesion to ice if the size of the cracks is small.

PMID- 23009386
TI  - Molecular insight into propeptide-protein interactions in cathepsins L and O.
AB  - Cathepsins are mammalian papain-like cysteine proteases that play an important
      role in numerous physiological and pathological processes. In the present study,
      various molecular dynamics (MD) simulations of pro- and mature human cathepsins L
      and O were performed. This study is the first to report MD simulations to
      complement the initial model structure of (pro-)cathepsin O through
      conformational sampling, thus offering insight into the maturation of
      procathepsin O, which to date has not been described experimentally. The overall
      fold of (pro-)cathepsin O appears very similar to that of (pro-)cathepsin L. The
      propeptide binding loop (PBL)-propeptide interface of both procathepsins is found
      to form a stable two-stranded beta-sheet. Additional stabilization of the PBL
      propeptide interface is provided by hydrophobic side chain contacts in
      procathepsin L, whereas this seems to be due to charge-dipole interactions in
      procathepsin O. Introduction of two mutations (L147P and G148P) into procathepsin
      O entails a significant loss of hydrogen bonding, disabling formation of the
      interfacial beta-sheet. Simulations at different protonation states suggest that
      procathepsin L is more sensitive to a change in pH than procathepsin O. Potential
      differences between the maturation of procathepsin O and procathepsin L inferred
      from the MD simulations might be caused by (i) stronger PBL-propeptide
      interactions in procathepsin O due to salt-bridge formation across the interface,
      (ii) more limited entropic gain of the propeptide of procathepsin O upon release
      into the bulk solvent due to diverse conformational states sampled in the bound
      state, (iii) more pronounced entropic loss of the PBL in procathepsin O upon
      substrate binding caused by diverse conformational states sampled in the free,
      mature enzyme, and (iv) lower sensitivity of procathepsin O to pH change caused
      by the presence of fewer carboxylate groups at the PBL-propeptide interface.

PMID- 23009387
TI  - Cost-effectiveness of vaccination with a quadrivalent HPV vaccine in Germany
      using a dynamic transmission model.
AB  - INTRODUCTION: Persistent infections with human papillomavirus (HPV) are a
      necessary cause of cervical cancer and are responsible for important morbidity in
      men and women. Since 2007, HPV vaccination has been recommended and funded for
      all girls aged 12 to 17 in Germany. A previously published cost-effectiveness
      analysis, using a static model, showed that a quadrivalent HPV vaccination
      programme for 12-year-old girls in Germany would be cost effective. Here we
      present the results from a dynamic transmission model that can be used to
      evaluate the impact and cost-effectiveness of different vaccination schemas.
      METHODS: We adapted a HPV dynamic transmission model, which has been used in
      other countries, to the German context. The model was used to compare a cervical
      cancer screening only strategy with a strategy of combining vaccination of
      females aged 12-17 years old and cervical cancer screening, based on the current
      recommendations in Germany. In addition, the impact of increasing vaccination
      coverage in this cohort of females aged 12-17 years old was evaluated in
      sensitivity analysis. RESULTS: The results from this analysis show that the
      current quadrivalent HPV vaccination programme of females ages 12 to 17 in
      Germany is cost-effective with an ICER of 5,525?/QALY (quality adjusted life
      year). The incremental cost-effectiveness ratio (ICER) increased to 10,293?/QALY
      when the vaccine effects on HPV6/11 diseases were excluded. At steady state, the
      model predicted that vaccinating girls aged 12 to 17 could reduce the number of
      HPV 6/11/16/18-related cervical cancers by 65% and genital warts among women and
      men by 70% and 48%, respectively. The impact on HPV-related disease incidence and
      costs avoided would occur relatively soon after initiating the vaccine programme,
      with much of the early impact being due to the prevention of HPV6/11-related
      genital warts. CONCLUSIONS: These results show that the current quadrivalent HPV
      vaccination and cervical cancer screening programmes in Germany will
      substantially reduce the incidence of cervical cancer, cervical intraepithelial
      neoplasia (CIN) and genital warts. The evaluated vaccination strategies were all
      found to be cost-effective. Future analyses should include more HPV-related
      diseases.

PMID- 23009388
TI  - The association of age at first start with career length in the Australian
      Thoroughbred racehorse population.
AB  - REASONS FOR PERFORMING STUDY: Studies of Thoroughbred racing populations have
      provided evidence of a positive effect on racing careers for horses that commence
      racing as 2-year-olds. Currently, research investigating the presence of this
      effect in the Australian Thoroughbred racing population is limited. OBJECTIVES:
      To investigate the association between age at first start and career length in
      the Australian Thoroughbred population and estimate the risk of racing retirement
      for horses racing in Australia based on age at first start, career earnings,
      number of starts as a 2-year-old and distance raced. METHODS: Data were collected
      for Thoroughbreds, born on or after 1 January 1998, that had raced between 1
      August 2000 and 22 February 2011 in Australia. A Kaplan-Meier survival curve,
      stratified by age group, was produced for career length. A Cox proportional
      hazard model was fitted to assess factors influencing the risk of retirement from
      racing. The model included sex, age at first start, career earnings, number of
      starts as a 2-year-old, distance raced and appropriate interaction terms.
      RESULTS: The study population included 117,088 horses. Geldings had significantly
      (P<0.001) longer careers than females and intact males, and females had
      significantly (P<0.001) longer careers than intact males. Risk of retirement from
      racing decreased with a younger age at first start, a higher number of starts as
      a 2-year-old, and a longer average distance raced. For intact males, the risk of
      retirement from racing increased as earnings increased, while for females and
      geldings the risk of retirement from racing decreased as earnings increased.
      CONCLUSIONS AND POTENTIAL RELEVANCE: The introduction of young Thoroughbreds to
      racing appears to have no apparent adverse effects on these horses racing in
      Australia. The impact of some risk factors associated with retirement from racing
      varied between sexes and should be considered when evaluating career outcomes.

PMID- 23009389
TI  - Analysis of serum cytokine levels in children with chronic cough associated with
      Toxocara canis infection.
AB  - Toxocara infection is associated with an increased prevalence of airway symptoms
      and may be a possible aetiologic agent of chronic cough. The occurrence of
      toxocariasis in Hungary is mild and/or sporadic. The purpose of this study was to
      investigate the levels of serum cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, IL-10,
      IL-13, IFN-gamma and TNF-alpha) and total IgE, the blood eosinophil count, the
      results of skin prick and non-specific bronchus provocation tests in Toxocara
      seropositive children with chronic cough relative to those in healthy controls.
      The patients exhibited moderate eosinophilia, significantly elevated levels of
      serum total IgE, IL-6, IL-10, IL-13 and IFN-gamma, and higher skin reactivity to
      common allergens, whereas the bronchial hyperreactivity was similar in the two
      groups. The protective proinflammatory cytokines (IL-6, IFN-gamma and IL-13) in
      association with the anti-inflammatory cytokine (IL-10) were simultaneously
      increased in Toxocara-infected children with chronic cough. During infections,
      the activation and suppression of immune processes occur simultaneously and
      cytokines of Th1/Th2 and regulatory T cells contribute to the regulation of the
      immune response evoked by helminth infections (depending on the parasite load,
      the timing and duration of the infection and the status of the host immune
      system).

PMID- 23009391
TI  - Multifunctional nanoparticles of Fe(3)O(4)@SiO(2)(FITC)/PAH conjugated the
      recombinant plasmid of pIRSE2-EGFP/VEGF(165) with dual functions for gene
      delivery and cellular imaging.
AB  - OBJECTIVES: Technologies to increase tissue vascularity are critically important
      to the fields of tissue engineering and cardiovascular medicine. Angiogenic
      factors, like VEGF, have been widely investigated to induce vascular endothelial
      cell proliferation and angiogenesis for establishing a vascular network. However,
      effective transport of VEGF gene to target cells with minimal side effects
      remains a challenge despite the use of unique viral and non-viral delivery
      approaches. METHODS: This study presents a novel gene delivery system of
      fluorescein isothiocyanate (FITC) doped and poly(allylamine hydrochloride) (PAH)
      grafted Fe(3)O(4)@SiO(2) nanoparticles, which allows efficient loading of pVEGF
      to form Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes for VEGF gene delivery and
      cellular imaging. RESULTS: The nanocomplexes maintain their superparamagnetic
      property in the silica composites at room temperature, reaching a saturation
      magnetization value of 5.19 emu/g of material, and no appreciable change in
      magnetism even after PAH modification. The quantitative analysis of cellular
      internalization into the living human umbilical vein endothelial cells (HUVECs)
      demonstrated that the Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could be
      entirely internalized by HUVECs, and exhibit high VEGF gene expression and an
      innocuous toxic profile. The magnetic resonance (MR) images showed that the
      superparamagnetic iron oxide core of Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF
      nanocomplexes could also act as a contrast agent for MR imaging. This property
      provides a benefit for monitoring gene delivery. CONCLUSION: These data highlight
      multifunctional Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes as an attractive
      platform for gene delivery of angiogenesis, and also making it a potential
      candidate of nanoprobes for cellular fluorescent imaging or MR imaging.

PMID- 23009392
TI  - An algorithm for chemical genomic profiling that minimizes batch effects: bucket
      evaluations.
AB  - BACKGROUND: Chemical genomics is an interdisciplinary field that combines small
      molecule perturbation with traditional genomics to understand gene function and
      to study the mode(s) of drug action. A benefit of chemical genomic screens is
      their breadth; each screen can capture the sensitivity of comprehensive
      collections of mutants or, in the case of mammalian cells, gene knock-downs,
      simultaneously. As with other large-scale experimental platforms, to compare and
      contrast such profiles, e.g. for clustering known compounds with uncharacterized
      compounds, a robust means to compare a large cohort of profiles is required.
      Existing methods for correlating different chemical profiles include diverse
      statistical discriminant analysis-based methods and specific gene filtering or
      normalization methods. Though powerful, none are ideal because they typically
      require one to define the disrupting effects, commonly known as batch effects, to
      detect true signal from experimental variation. These effects are not always
      known, and they can mask true biological differences. We present a method, Bucket
      Evaluations (BE) that surmounts many of these problems and is extensible to other
      datasets such as those obtained via gene expression profiling and which is
      platform independent. RESULTS: We designed an algorithm to analyse chemogenomic
      profiles to identify potential targets of known drugs and new chemical compounds.
      We used levelled rank comparisons to identify drugs/compounds with similar
      profiles that minimizes batch effects and avoids the requirement of pre-defining
      the disrupting effects. This algorithm was also tested on gene expression
      microarray data and high throughput sequencing chemogenomic screens and found the
      method is applicable to a variety of dataset types. CONCLUSIONS: BE, along with
      various correlation methods on a collection of datasets proved to be highly
      accurate for locating similarity between experiments. BE is a non-parametric
      correlation approach, which is suitable for locating correlations in somewhat
      perturbed datasets such as chemical genomic profiles. We created software and a
      user interface for using BE, which is publically available.

PMID- 23009393
TI  - Co-inheritance of HNF1a and GCK mutations in a family with maturity-onset
      diabetes of the young (MODY): implications for genetic testing.
AB  - OBJECTIVE: To determine the genetic basis of dominant early-onset diabetes
      mellitus in two families. PATIENTS AND METHODS: Molecular analysis by PCR
      sequencing of the promoter, the 5' untranslated region (UTR) and exons of both
      GCK and HNF1A genes was carried out in two families with clinically diagnosed
      dominant diabetes mellitus. RESULTS: The novel HNF1A c.-154_-160TGGGGGT mutation,
      located in the 5' UTR, was present in several members of the two families in the
      heterozygous state. Interestingly, the GCK p.Y61X mutation was also identified in
      three members of one of the families, and two of them carried both mutations in
      heterozygosis. To the best of our knowledge, this is the first report of the co
      inheritance of GCK and HNF1A mutations and the coexistence of maturity-onset
      diabetes of the young (MODY) 2, MODY 3 and unusual MODY 2-3 genotypes in the same
      family. CONCLUSIONS: Carriers of both GCK and HNF1A mutations manifested a
      typical MODY 3 phenotype and showed that the presence of a second mutation in the
      GCK gene apparently did not modify the clinical outcome, at least at the time of
      this study. Our data show that co-inheritance of MODY 2 and MODY 3 mutations
      should be considered, at least in some cases, for accurate genetic testing.

PMID- 23009394
TI  - Fragile X-associated tremor/ataxia syndrome (FXTAS) in grey zone carriers.
AB  - The grey zone (GZ; 45-54 CGG repeats in the FMR1 gene) is considered a normal
      allele; however, several studies have found a high frequency of GZ in movement
      disordered populations. Here, we describe neurological features of fragile X
      associated tremor/ataxia syndrome (FXTAS) in two carriers of GZ alleles, although
      FXTAS has been defined as occurring only in premutation carriers (55-200 CGG
      repeats). Both patients had family members who had premutation and were diagnosed
      with FXTAS. The presence of relatively high GZ alleles with elevated fragile X
      mental retardation 1 mRNA (FMR1-mRNA) combined with a family history of FXTAS
      that may represent a facilitating genetic background for FXTAS are the factors
      that led to the presence of FXTAS in these individuals with a GZ allele. Further
      research into clinical involvement of GZ alleles is recommended and the
      definition of FXTAS may require revision.

PMID- 23009396
TI  - GM1 cluster mediates formation of toxic Abeta fibrils by providing hydrophobic
      environments.
AB  - The conversion of soluble, nontoxic amyloid beta-proteins (Abeta) to aggregated,
      toxic forms rich in beta-sheets is considered to be a key step in the development
      of Alzheimer's disease. Accumulating evidence suggests that lipid-protein
      interactions play a crucial role in the aggregation of amyloidogenic proteins
      like Abeta. Our group has previously reported that amyloid fibrils of Abeta
      formed on membranes containing clusters of GM1 ganglioside (M-fibrils) exhibit
      greater cytotoxicity than fibrils formed in aqueous solution (W-fibrils) [   
      Okada (  2008  )   J. Mol. Biol.  382  ,   1066 - 1074  ]. W-fibrils are
      considered to consist of in-register parallel beta-sheets. However, the precise
      molecular structure of M-fibrils and force driving the formation of toxic fibrils
      remain unclear. In this study, we hypothesized that low-polarity environments
      provided by GM1 clusters drive the formation of toxic fibrils and compared the
      structure and cytotoxicity of W-fibrils, M-fibrils, and aggregates formed in a
      low-polarity solution mimicking membrane environments. First, we determined
      solvent conditions which mimic the polarity of raftlike membranes using Abeta-(1
      40) labeled with the 7-diethylaminocoumarin-3-carbonyl dye. The polarity of a
      mixture of 80% 1,4-dioxane and 20% water (v/v) was found to be close to that of
      raftlike membranes. Abeta-(1-40) formed amyloid fibrils within several hours in
      80% dioxane (D-fibrils) or in the presence of raftlike membranes, whereas a much
      longer incubation time was required for fibril formation in a conventional
      buffer. D-fibrils were morphologically similar to M-fibrils. Fourier-transform
      infrared spectroscopy suggested that M-fibrils and D-fibrils contained
      antiparallel beta-sheets. These fibrils had greater surface hydrophobicity and
      exhibited significant toxicity against human neuroblastoma SH-SY5Y cells, whereas
      W-fibrils with less surface hydrophobicity were not cytotoxic. We concluded that
      ganglioside clusters mediate the formation of toxic amyloid fibrils of Abeta with
      an antiparallel beta-sheet structure by providing less polar environments.

PMID- 23009395
TI  - Hyperconjugation-mediated solvent effects in phosphoanhydride bonds.
AB  - Density functional theory and natural bond orbital analysis are used to explore
      the impact of solvent on hyperconjugation in methyl triphosphate, a model for
      "energy rich" phosphoanhydride bonds, such as found in ATP. As expected, dihedral
      rotation of a hydroxyl group vicinal to the phosphoanhydride bond reveals that
      the conformational dependence of the anomeric effect involves modulation of the
      orbital overlap between the donor and acceptor orbitals. However, a
      conformational independence was observed in the rotation of a solvent hydrogen
      bond. As one lone pair orbital rotates away from an optimal antiperiplanar
      orientation, the overall magnitude of the anomeric effect is compensated
      approximately by the other lone pair as it becomes more antiperiplanar.
      Furthermore, solvent modulation of the anomeric effect is not restricted to the
      antiperiplanar lone pair; hydrogen bonds involving gauche lone pairs also affect
      the anomeric interaction and the strength of the phosphoanhydride bond. Both
      gauche and anti solvent hydrogen bonds lengthen nonbridging O-P bonds, increasing
      the distance between donor and acceptor orbitals and decreasing orbital overlap,
      which leads to a reduction of the anomeric effect. Solvent effects are additive
      with greater reduction in the anomeric effect upon increasing water coordination.
      By controlling the coordination environment of substrates in an active site,
      kinases, phosphatases, and other enzymes important in metabolism and signaling
      may have the potential to modulate the stability of individual phosphoanhydride
      bonds through stereoelectronic effects.

PMID- 23009397
TI  - Effects of positive cognitions and resourcefulness on caregiver burden among
      caregivers of persons with dementia.
AB  - Currently, 5.4 million persons in the USA are diagnosed with dementia, and this
      number is projected to rise to 7.7 million by the year 2030. Family caregivers
      provide up to 80% of the care needed by persons with dementia and published work
      suggests that caring for persons with dementia can be very costly to caregivers'
      health. This study examined the mediating and the moderating effects of positive
      cognitions on the relationship between caregiver burden and resourcefulness in 80
      caregivers of persons with dementia. A descriptive, correlational, and cross
      sectional design was used in this study. The researcher contacted the
      administrators at the Alzheimer's Association early stage programs in
      Southeastern Wisconsin and questionnaires were distributed to interested
      caregivers. Positive cognitions explained 31% of the variance in resourcefulness
      (F (1, 78) = 35.46, P < 0.001) and as positive cognitions increased, caregivers'
      resourcefulness increased. Positive cognitions were found to be a mediator as
      evidenced by a substantial drop in the beta weight of caregiver burden from B = 
      0.28 to B = -0.11 when positive cognitions were entered into the equation.
      Interventions to strengthen positive thinking among caregivers of persons with
      dementia are needed to help caregivers overcome their burden.

PMID- 23009398
TI  - Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter
      activation.
AB  - BACKGROUND: The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1)
      is a powerful activator of the NF-kappaB pathway, a property critical for HTLV-1
      induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this
      pathway at a cytoplasmic level by activating the IkappaB kinase (IKK) complex and
      at a nuclear level by enhancing the binding of the NF-kappaB factor RelA to its
      cognate promoters and by forming nuclear bodies, believed to represent
      transcriptionally active structures. In previous studies, we reported that Tax
      ubiquitination and SUMOylation play a critical role in Tax localization and NF
      kappaB activation. Indeed, analysis of lysine Tax mutants fused or not to
      ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination
      first intervenes to activate IKK while Tax SUMOylation is subsequently required
      for promoter activation within Tax nuclear bodies. However, recent studies
      showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus
      or the cytoplasm and that SUMOylated Tax can serve as substrate for
      ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate
      redundant rather than successive functions. RESULTS: In this study, we analyzed
      the properties of a new Tax mutant that is properly ubiquitinated, but defective
      for both nuclear body formation and SUMOylation. We report that reducing Tax
      SUMOylation and nuclear body formation do not alter the ability of Tax to
      activate IKK, induce RelA nuclear translocation, and trigger gene expression from
      a NF-kappaB promoter. Importantly, potent NF-kappaB promoter activation by Tax
      despite low SUMOylation and nuclear body formation is also observed in T cells,
      including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies
      are hardly observed in HTLV-1-infected T cells. Finally, we provide direct
      evidence that the degree of NF-kappaB activation by Tax correlates with the level
      of Tax ubiquitination, but not SUMOylation. CONCLUSIONS: These data reveal that
      the formation of Tax nuclear bodies, previously associated to transcriptional
      activities in Tax-transfected cells, is dispensable for NF-kappaB promoter
      activation, notably in CD4+ T cells. They also provide the first evidence that
      Tax SUMOylation is not a key determinant for Tax-induced NF-kappaB activation.

PMID- 23009400
TI  - 37th Congress of the Society of Biomechanics. Editorial.

PMID- 23009402
TI  - Biomechanics for computer-assisted surgery.

PMID- 23009399
TI  - Evaluation of the inhibitory effects of quercetin-related flavonoids and tea
      catechins on the monoamine oxidase-A reaction in mouse brain mitochondria.
AB  - Quercetin, a typical dietary flavonoid, is thought to exert antidepressant
      effects by inhibiting the monoamine oxidase-A (MAO-A) reaction, which is
      responsible for regulation of the metabolism of the neurotransmitter 5
      hydroxytryptamine (5-HT) in the brain. This study compared the MAO-A inhibitory
      activity of quercetin with those of O-methylated quercetin (isorhamnetin,
      tamarixetin), luteolin, and green tea catechins ((-)-epicatechin, (-)-epicatechin
      gallate, (-)-epigallocatechin, and (-)-epigallocatechin gallate) by measuring the
      formation of the oxidative deamination product of 5-HT, 5-hydroxyindole aldehyde
      (5-HIAL), in mouse brain mitochondria. Quercetin was inferior to luteolin in the
      inhibition of MAO-A activity, whereas isorhamnetin, tamarixetin, and tea
      catechins scarcely exerted inhibitory activity. Quercetin did not affect MAO-A
      activity in mouse intestinal mitochondria, indicating that it does not evoke side
      effects on the metabolism of dietary monoamines in the gut. These data suggest
      that quercetin is a weak (but safe) MAO-A inhibitor in the modulation of 5-HT
      levels in the brain.

PMID- 23009403
TI  - Nanoreinforcement of hydroxyapatite coatings on titanium for osseointegration of
      orthopaedic implants.

PMID- 23009404
TI  - Equine superficial digital flexor tendon force and axial speed of sound: a
      calibration method under clinical conditions.

PMID- 23009405
TI  - A purely mechanical model to explore amoeboid cell migration.

PMID- 23009406
TI  - Biofluidics of animal morphogenesis: does evolution follow stream lines?

PMID- 23009407
TI  - Effect of macroscopic loading on nanoscopic signal for cellular activity.

PMID- 23009408
TI  - A reactive model to predict the periprosthetic healing.

PMID- 23009409
TI  - Numerical analysis of keloid scar in the presternal area.

PMID- 23009410
TI  - Discrete model combined with mimetic microfluidic chips to study cell growth in
      porous scaffold under flow conditions.

PMID- 23009411
TI  - Inverse problems for the determination of traction forces by cells on a
      substrate: a comparison of two methods.

PMID- 23009412
TI  - On the air permeability of Populus pit.

PMID- 23009413
TI  - Characterisation of membrane elastic properties of capsules flowing in a square
      section microfluidic channel.

PMID- 23009414
TI  - Shear-induced diffusion in a red blood cell suspension.

PMID- 23009415
TI  - Ultrasonic assessment of arterial wall elasticity: the palpography technique
      revisited.

PMID- 23009416
TI  - Patient-specific finite element model of the buttocks for pressure ulcer
      prevention--linear versus non-linear modelling.

PMID- 23009417
TI  - Using a 3D biomechanical model to improve a light aspiration device for in vivo
      soft tissue characterisation.

PMID- 23009418
TI  - Patient-specific numerical model of soft tissues in the compressed leg:
      application to six subjects.

PMID- 23009419
TI  - Computational flow dynamics based on an intracranial aneurysm animal model.

PMID- 23009420
TI  - Influence of blood shear-thinning behaviour on flow dynamics in abdominal aortic
      aneurysm in vitro compliant model.

PMID- 23009421
TI  - Geometrical orifice area compared to effective orifice area of valvular mitral
      bioprosthesis: in vitro study.

PMID- 23009422
TI  - Flow and particles deposition in anatomically realistic airways.

PMID- 23009423
TI  - Boundary conditions in arterial flows and evaluation of reflection indices.

PMID- 23009424
TI  - Comparing different numerical methods for solving arterial 1D flows in networks.

PMID- 23009425
TI  - Non-invasive method for measuring local pulse wave velocity in arteries: part II.

PMID- 23009426
TI  - Control of brain blood flow by capillaries: a simulation study in an anatomically
      accurate large human vascular network.

PMID- 23009427
TI  - Glottal motion and its impact on the respiratory flow.

PMID- 23009428
TI  - A numerical study on the influence of CT scan orientation for mandible
      biomechanical simulation.

PMID- 23009429
TI  - Image-based patient-specific simulation: a computational modelling of the human
      left heart haemodynamics.

PMID- 23009430
TI  - 3D geometrical modelling of adolescent idiopathic scoliosis.

PMID- 23009431
TI  - Pressure drop reconstruction in the aqueduct of sylvius from MRI acquisitions.

PMID- 23009432
TI  - Finite element vertebral model for fracture risk prediction: comparison of a full
      CT-based model versus two media simplified model, a preliminary study.

PMID- 23009433
TI  - In vitro validation of non-invasive aortic compliance measurements using MRI.

PMID- 23009434
TI  - Development of a model to analyse foot biomechanics using dynamic 3D surface
      scanning.

PMID- 23009435
TI  - The effect of the thermal treatment on the stress-corrosion of nickel-titanium
      wires.

PMID- 23009436
TI  - Nanoindentation characterisation of poly(DL-lactide)/collagen nanocomposites.

PMID- 23009437
TI  - The influence of sterilisation processes on the micromechanical properties of
      polyamide fibre-reinforced PDMS composites for orthopaedic applications.

PMID- 23009438
TI  - Fatigue life prediction of cardiovascular stent using finite element method.

PMID- 23009439
TI  - Variation of foot-to-foot resistance measured by body fat analysers with
      electrode geometry and contact area.

PMID- 23009440
TI  - Numerical durability evaluation of Nitinol stent.

PMID- 23009441
TI  - A human skin culture system for a wound-healing model.

PMID- 23009442
TI  - A new optical feedback interferometer for measuring red blood cell velocity
      distributions in individual capillaries: a feasibility study in microchannels.

PMID- 23009443
TI  - Quasi-static failure properties of the human gastro-colic ligament.

PMID- 23009444
TI  - Non-invasive method for measuring local pulse wave velocity in arteries: part I.

PMID- 23009445
TI  - Thermo-mechanics of growth and mass transfer: morphogenesis of seashells.

PMID- 23009446
TI  - Study of the renal cortex by light scattering.

PMID- 23009447
TI  - Flow dynamics characterisation of a novel perfusion-type bioreactor for bone
      tissue engineering.

PMID- 23009448
TI  - Morphometric classification of cranial vault deformation in trigonocephaly: a
      preliminary study in 10 patients.

PMID- 23009449
TI  - Comparative approach of predatory/feeding behaviours in Tetrapods.

PMID- 23009450
TI  - Morphometric characterisation of an arboreal lizard (Anolis marmoratus
      marmoratus).

PMID- 23009451
TI  - Use of motion trackers for equine locomotion analysis to implement a horse
      simulator.

PMID- 23009452
TI  - 3D accelerometric assessment of the gait of dogs with cranial cruciate ligament
      rupture.

PMID- 23009453
TI  - Use of a 3D dynamometric horseshoe for the measurement of grip parameters in a
      horse cantering on right and left circles on two surfaces.

PMID- 23009454
TI  - Prey effect on capture kinematics in Pogona vitticeps (Iguania, Squamata).

PMID- 23009455
TI  - Ballistic food transport in birds: the example of Casuarius casuarius.

PMID- 23009456
TI  - Evaluation of the effectiveness of bandages on restricting carpus range of motion
      in healthy dogs at a walk using electrogoniometry.

PMID- 23009457
TI  - Effects of ground surface on the equine superficial digital flexor tendon loading
      at the walk and trot.

PMID- 23009458
TI  - Synergies between humanoid robotics and biomechanics for motion generation.

PMID- 23009459
TI  - Simulating the effect of upper-body inertia on human balance recovery.

PMID- 23009460
TI  - A machine learning approach to reaching tasks.

PMID- 23009461
TI  - Biomechanical versus robotic indices to assess isometric force generation
      capabilities.

PMID- 23009462
TI  - Generation of human-like motion on anthropomorphic systems using inverse
      dynamics.

PMID- 23009463
TI  - Comparison of muscle loadings between power and pinch grip tasks.

PMID- 23009464
TI  - Effect of velocity on muscular coordination during isokinetic lifting: a
      preliminary study on healthy subjects.

PMID- 23009465
TI  - Specific neuromuscular fatigue induced by repetitive isoload concentric knee
      extension.

PMID- 23009466
TI  - Biomechanical model of the ankle to estimate the musculotendinous forces during
      an isometric plantar flexion.

PMID- 23009467
TI  - Gait abnormalities in type 1 myotonic muscular dystrophy: 3D motion analysis,
      energy cost and surface EMG.

PMID- 23009468
TI  - Computation of the mechanical power of a manual wheelchair user in actual
      conditions: preliminary results.

PMID- 23009469
TI  - Gait analysis of amputee people in limiting situations of daily living.

PMID- 23009470
TI  - Description and classification of the effect of hamstrings lengthening in
      cerebral palsy children multi-site surgery.

PMID- 23009471
TI  - Dynamic footprint analysis by time-of-flight camera.

PMID- 23009472
TI  - Joint and segment coordinate systems revisited.

PMID- 23009473
TI  - Improvement of musculoskeletal model inputs: adjustment of acceleration by
      dynamic optimisation.

PMID- 23009474
TI  - Froude and Strouhal dimensionless numbers to study human gait: an experimental
      approach.

PMID- 23009475
TI  - Multi-body optimisation with deformable ligament constraints: influence of
      ligament geometry.

PMID- 23009476
TI  - Feasibility of incorporating a soft tissue artefact model in multi-body
      optimisation.

PMID- 23009477
TI  - Biomechanics of the human hip joint.

PMID- 23009478
TI  - A non invasive protocol for the in vivo estimation of lumbar spine kinematics.

PMID- 23009479
TI  - Kinematics of human spine during hippotherapy.

PMID- 23009480
TI  - Influence of lower limbs strength on trunk flexion and extension in chronic low
      back pain patients.

PMID- 23009481
TI  - Validation of a volumic model to obtain personalized body segment inertial
      parameters for people sitting in a wheelchair.

PMID- 23009482
TI  - Evolutions of the wheelchair user's centre of mass and centre of pressure
      according to the seat fore-aft position during sprinting: a case study of an
      elite wheelchair tennis player.

PMID- 23009483
TI  - Analysis of the agreement between the Fortius cycling ergometer and the PowerTap
      powermeter PO during time trials of 6 and 30 min.

PMID- 23009484
TI  - Evolution of pedalling biomechanics during a Wingate test for different cyclist
      types: a preliminary study.

PMID- 23009485
TI  - New performance indicators for BMX riders.

PMID- 23009486
TI  - Comparison of motor strategy between confirmed and professional cyclists during
      an incremental maximal test.

PMID- 23009487
TI  - Experimental and computational studies of the front crawl swimming, at the end of
      the entry-and-stretch phase.

PMID- 23009488
TI  - Does bilateral index differ between countermovement jump, drop jump and squat
      jump?

PMID- 23009489
TI  - Method to assess the effect of the position in the starting blocks on the
      acceleration phase of an elite female sprinter.

PMID- 23009490
TI  - On the effect of playing surfaces on lower limb intersegmental loads.

PMID- 23009491
TI  - Effects of different types of tyres and surfaces on the power output in the
      mountain bike field conditions: a preliminary study.

PMID- 23009492
TI  - Design and prototyping of a system for ankle spasticity quantification.

PMID- 23009493
TI  - Minimal predicted distance: a kinematic cue to investigate collision avoidance
      between walkers.

PMID- 23009494
TI  - Normal/tangential force proportion during steering under simulation condition.

PMID- 23009495
TI  - Development of a 3D accelerometric device for gait analysis in dogs.

PMID- 23009496
TI  - Is the time of release during a precision throwing task, predictable?

PMID- 23009497
TI  - Low-cost motion capture systems in practice.

PMID- 23009498
TI  - Quantifying standing posture during multi-joint movements.

PMID- 23009499
TI  - Quantification of facial movements by motion capture.

PMID- 23009500
TI  - New statistic analysis for BMX rider.

PMID- 23009501
TI  - Simulation of muscle retraction in cerebral palsy. Validation of a decision
      support system for surgical lengthening of contractured muscles.

PMID- 23009502
TI  - Atypical EMG activation patterns of the elbow extensors after complete C6
      tetraplegia during isometric contractions: a case report.

PMID- 23009503
TI  - Analysis of revolution time variability in cycling pattern.

PMID- 23009504
TI  - Passive skeletal muscle mechanical behaviour: considerations for constitutive
      modelling.

PMID- 23009505
TI  - Epidemiological study applied to the design of wrist guard.

PMID- 23009506
TI  - Mechanical characterisation under cycling loading of humerus cortical bone.

PMID- 23009507
TI  - Geometric variability of ribs, costal cartilages and sternums from childhood to
      teenage.

PMID- 23009508
TI  - Analysis of the cortical bone thickness of human thorax based on multi-scale
      imaging techniques.

PMID- 23009509
TI  - Characterisation of the difference in fracture mechanics between children and
      adult cortical bone.

PMID- 23009510
TI  - Quasi-static failure properties of the human gastro-colic ligament.

PMID- 23009511
TI  - Influence of the velocity on the in vitro fracture of the femoral neck for
      lateral compression tests.

PMID- 23009512
TI  - Cosserat 3D anisotropic models of trabecular bone from the homogenisation of the
      trabecular structure.

PMID- 23009513
TI  - Links between microstructural properties of cancellous bone and its mechanical
      response to different strain rates.

PMID- 23009514
TI  - In vivo biomechanical response of ovine heads to shaken baby syndrome events.

PMID- 23009515
TI  - Influence of pre-crash driver posture on injury outcome: airbag interaction with
      human upper extremities.

PMID- 23009516
TI  - Geometrical personalisation of human FE model using palpable markers on
      volunteers.

PMID- 23009517
TI  - Injury criteria of knee joint regarding car-pedestrian impact environments.

PMID- 23009518
TI  - Comparison of geometrical models of cranial bone samples for the identification
      of an apparent elastic modulus.

PMID- 23009519
TI  - Investigation on the interindividual differences influence on submarining in
      frontal crash.

PMID- 23009520
TI  - Development and validation of a bicycle helmet: assessment of head injury risk
      under standard impact conditions.

PMID- 23009521
TI  - On the use of Hopkinson bar-bending apparatus to study soft impact on porcine
      ribs.

PMID- 23009522
TI  - Experimental and numerical characterisation of the mechanical behaviour of the
      cranial bone.

PMID- 23009523
TI  - In vitro production and biomechanical experimental analysis of thoracolumbar
      burst fractures.

PMID- 23009524
TI  - Peri-operative exercise training programme for hip arthroplasty: the effect on
      locomotion.

PMID- 23009525
TI  - An optimisation approach of a new dynamic spinal device.

PMID- 23009526
TI  - Implant fixation of novel and commercial TMJ implants.

PMID- 23009527
TI  - Investigation of in-vivo hinge knee behaviour using a dynamic finite element
      model of the lower limb.

PMID- 23009528
TI  - Design a total hip prosthesis with modular channel under CAD environment.

PMID- 23009529
TI  - Parametric study of interstitial fluid flow in the bone lacuno-canalicular
      network.

PMID- 23009530
TI  - Mechanical coupling effects into a L3-L5 vertebral segment.

PMID- 23009531
TI  - Nanoindentation of intervertebral disc tissues localised by SHG imaging.

PMID- 23009532
TI  - Comparison of the effect of locking vs standard screws on the mechanical
      properties of bone-plate constructs in a comminuted diaphyseal fracture model.

PMID- 23009533
TI  - Measuring primary stability of cervical implant.

PMID- 23009534
TI  - A method to measure glenoid wear in 3D.

PMID- 23009535
TI  - Design and implementation of orthosis to improve gait of patients with
      hemiplegia.

PMID- 23009536
TI  - Assessing shoulder posture ergonomy thanks to a finite element analysis.

PMID- 23009537
TI  - Biomechanical testing of the primary stability of macro and micro-roughnesses
      acetabular cups: a numerical and an experimental study.

PMID- 23009538
TI  - Model of cancellous bone adaptation considering hypermineralised bone tissue.

PMID- 23009539
TI  - Achilles tendon force and axial speed of sound: a calibration method under
      clinical conditions.

PMID- 23009540
TI  - The bouncing mechanism of running in a transfemoral amputee wearing a blade
      prosthesis.

PMID- 23009541
TI  - Foot biomechanical modelling to study orthoses influence.

PMID- 23009542
TI  - The strain distribution for the natural and implanted hip joint articulation.

PMID- 23009543
TI  - Relevance of skin deformation to track the scapula during forward humeral
      elevations.

PMID- 23009544
TI  - Scapulo-thoracic kinematics in children: accuracy and reliability.

PMID- 23009545
TI  - A simple method to compare body and upper limb kinetics in the course of pointing
      task.

PMID- 23009546
TI  - Determination of force platform parameters during sit-to-stand movement in
      elderly: a preliminary study.

PMID- 23009547
TI  - Posture and chronic gonalgia in the elderly: contribution of osteopathic
      treatment.

PMID- 23009550
TI  - Gracilis muscle interposition with primary rectal without urethral repair for
      moderate sized rectourethral fistula caused by brachytherapy for prostate cancer:
      a case report.
AB  - INTRODUCTION: There is a 0.16% chance of a rectourethral fistula after prostate
      brachytherapy monotherapy using Palladium-103 or Iodine-125 implants. We present
      an unusual case report of a rectourethral fistula following brachyradiotherapy
      monotherapy for prostate adenocarcinoma. It was also associated with unusual
      management of the fistula. CASE PRESENTATION: A 58-year-old Caucasian man
      underwent brachyradiotherapy monotherapy as definitive treatment for verified
      intracapsular prostate adenocarcinoma receiving 56 Iodine-125 implants using a
      transrectal ultrasound-guided technique. The patient started to complain of
      severe perineal pain and mild rectal bleeding 15A months after
      brachyradiotherapy. A biopsy of mucosa of his anterior rectal wall was performed.
      A moderate sized rectourethral fistula was confirmed 23A months after
      implantation of Iodine-125 seeds. Laparoscopic sigmoidostomy and suprapubic
      cystostomy were then performed. Long-term cortisone applications in combination
      with 30 sessions of hyperbaric oxygen therapy, and antibacterial therapies were
      initiated due to necrotic infection. A gracilis muscle interposition to create a
      partition between the patient's rectum and urethra in conjunction with primary
      rectal repair but without urethral repair were performed 6 months later. The 3cm
      rectal defect was repaired via a 3cm-long horizontal perineal incision. The 1.5cm
      urethral defect just below the prostate was not repaired. The patient underwent
      an optic internal urethrotomy 3A months later for a 1.5cm-long urethral
      stricture. Several planned preventive urethral buginages were performed to avoid
      urethral stricture recurrence. At 12A months postoperatively, there were no signs
      of a fistula and cancer recurrence. He now has a normal voiding and anal
      continence. CONCLUSION: Severe rectal pain, bleeding, and local anterior necrotic
      proctitis are predictors of a rectourethral fistula. Urinary and fecal diversion
      is the first-step operation. Gracilis muscle interposition in conjunction with
      primary rectal repair but without urethral reconstruction is one of the
      reconstructive surgery options for moderate 2cm to 3cm rectourethral fistulas.
      Internal urethrotomy is a procedure for postoperative urethral strictures of
      1.5cm in length.

PMID- 23009548
TI  - Proteomic identification of MYC2-dependent jasmonate-regulated proteins in
      Arabidopsis thaliana.
AB  - BACKGROUND: MYC2, a basic helix-loop-helix (bHLH) domain-containing transcription
      factor, participates in the jasmonate (JA) signaling pathway and is involved in
      the modulation of diverse JA functions. However, a comprehensive list of MYC2
      dependent JA-responsive proteins has yet to be defined. RESULTS: In this paper,
      we report the comparative proteomics of wild-type (WT) plants and jin1-9, a MYC2
      mutant plant, in response to methyl jasmonate (MeJA) treatment. Proteins from
      mock/MeJA-treated jin1-9 and WT samples were extracted and separated by two
      dimensional gel electrophoresis. Twenty-seven JA-mediated proteins demonstrated
      differential expression modulated by MYC2. We observed that MYC2 negatively
      regulates the accumulation of JA-dependent indolic glucosinolate-related proteins
      and exhibits opposite effects on the biosynthetic enzymes involved aliphatic
      glucosinolate pathways. In addition, proteins involved in the tricarboxylic acid
      cycle and a majority of the MeJA-inducible proteins that are involved in multiple
      protective systems against oxidative stress were reduced in jin1-9/myc2 sample
      compared to the WT sample. These results support a positive role for MYC2 in
      regulating JA-mediated carbohydrate metabolism and oxidative stress tolerance.
      CONCLUSIONS: We have identified MYC2-dependent jasmonate-regulated proteins in
      Arabidopsis thaliana by performing two-dimensional gel electrophoresis and MALDI
      TOF/TOF MS analysis. The observed pattern of protein expression suggests that
      MYC2 has opposite effects on the biosynthetic enzymes of indolic and aliphatic
      glucosinolate pathways and positively regulates JA-mediated carbohydrate
      metabolism and oxidative stress tolerance-related proteins. Furthermore, it is
      very interesting to note that MYC2 plays opposite roles in the modulation of a
      subset of JA-regulated photosynthetic proteins during short-term and long-term JA
      signaling. This study will enhance our understanding of the function of MYC2 in
      JA signaling in Arabidopsis thaliana.

PMID- 23009552
TI  - Transdermal rotigotine for the perioperative management of restless legs
      syndrome.
AB  - BACKGROUND: Immobilisation, blood loss, sleep deficiency, and (concomitant)
      medications during perioperative periods might lead to acute exacerbation of
      symptoms in patients with the restless legs syndrome (RLS). Continuous
      transdermal delivery of the dopamine agonist rotigotine provides stable plasma
      levels over 24 h and may provide RLS patients with a feasible treatment option
      for perioperative situations. To assess the feasibility of use of rotigotine
      transdermal patch for the perioperative management of moderate to severe RLS,
      long-term data of an open-label extension of a rotigotine dose-finding study were
      retrospectively reviewed. METHODS: The data of all 295 patients who had entered
      the 5-year study were screened independently by two reviewers for the occurrence
      of surgical interventions during the study period. The following data were
      included in this post-hoc analysis: patient age, sex, surgical intervention and
      outcome, duration of hospital stay, rotigotine maintenance dose at the time of
      surgery, rotigotine dose adjustment, and continuation/discontinuation of
      rotigotine treatment. All parameters were analysed descriptively. No pre
      specified efficacy assessments (e.g. IRLS scores) were available for the
      perioperative period. RESULTS: During the study period, 61 surgical interventions
      were reported for 52 patients (median age, 63 years; 67% female); the majority of
      patients (85%) had one surgical intervention. The mean rotigotine maintenance
      dose at time of surgery was 3.1 +/- 1.1 mg/24 h. For most interventions (95%),
      rotigotine dosing regimens were maintained during the perioperative period.
      Administration was temporarily suspended in one patient and permanently
      discontinued in another two. The majority (96%) of the patients undergoing
      surgery remained in the study following the perioperative period and 30 of these
      patients (61%) completed the 5-year study. CONCLUSIONS: Although the data were
      obtained from a study which was not designed to assess rotigotine use in the
      perioperative setting, this post-hoc analysis suggests that treatment with
      rotigotine transdermal patch can be maintained during the perioperative period in
      the majority of patients and may allow for uninterrupted alleviation of RLS
      symptoms. TRIAL REGISTRATION: The 5-year rotigotine extension study is registered
      with ClinicalTrials.gov, identifier NCT00498186.

PMID- 23009553
TI  - Factors influencing foaling rate following colic surgery in pregnant Thoroughbred
      mares in Central Kentucky.
AB  - REASONS FOR PERFORMING STUDY: Clinical experience has suggested that foaling
      rates following colic surgery in the pregnant mare are influenced by days of
      gestation. This premise has not been supported in previous studies. We also aimed
      to determine the effects of other potential influencing factors. OBJECTIVE: To
      determine the influence of age of gestation on foaling rates in pregnant mares
      following colic surgery and evaluate the relationships between other factors and
      foaling rates. METHODS: Medical records of Thoroughbred mares, which had colic
      surgery performed from 1993 to 2007 at the Rood and Riddle Equine Hospital, were
      reviewed. Mares identified in the record as pregnant or bred within the previous
      15 days were included in this study. Age of the mare, date of surgery,
      gestational age, duration of colic at admission, packed cell volume at admission,
      surgical diagnosis, duration of general anaesthesia, intraoperative hypotension,
      intraoperative hypoxaemia and post operative signs of endotoxaemia were recorded.
      A mare was considered to have a live foal if that foal was registered with the
      North American Jockey Club. RESULTS: Of the 228 mares, where pregnancy had been
      confirmed, 152 (66.7%) had a live foal registered after surgery. Mares bred <40
      days before surgery had a lower foaling rate compared with mares undergoing
      surgery >=40 days after breeding: 48.7% vs. 69.8% (odds ratio [OR] = 0.41 [95%
      confidence interval (CI) 0.20-0.83], P = 0.012). Foaling rate was also influenced
      by mare's age (P = 0.008) and duration of colic signs before surgery (P = 0.03).
      CONCLUSIONS: The prognosis for a live foal after colic surgery in the pregnant
      Thoroughbred mare is significantly better if the mare is <=15 years of age and
      >=40 days of gestation. POTENTIAL RELEVANCE: The results of this study are useful
      for clinicians offering a prognosis for a live foal following colic surgery in
      pregnant mares.

PMID- 23009554
TI  - Changes in beta-adrenergic neurotransmission during postoperative ileus in rat
      circular jejunal muscle.
AB  - BACKGROUND: To explore postoperative changes in beta-adrenergic neurotransmission
      that participate in pathophysiology of postoperative ileus. METHODS: Contractile
      activity of circular jejunal muscle strips was studied. Groups (n = 6/group)
      were: naive controls, sham controls 1 and 7 days after laparotomy, and rats 12 h,
      1, 3, and 7 days after laparotomy with standardized small bowel manipulation
      (postoperative ileus). Dose-responses to the beta-agonist isoprenaline (3 * 10(
      10) - 10(-7) mol L(-1)) were studied in presence/absence of tetrodotoxin (global
      neural blockade; 10(-6) mol L(-1) ), N6-(1-iminoethyl)-l-lysine (inhibition of
      inducible nitric oxide synthesis; 10(-4) mol L(-1)), nimesulide (cyclooxygenase-2
      inhibition; 10(-5) mol L(-1)), or propranolol (beta-blockade; 5 * 10(-6) mol L(
      1)). Histochemistry for inflammatory cells and intestinal transit were studied.
      KEY RESULTS: Intramural inflammation and delayed transit (postoperative ileus)
      occurred only in ileus groups. The inhibitory potential of isoprenaline decreased
      in all postoperative groups including sham (P < 0.05). Tetrodotoxin enhanced
      isoprenaline-induced inhibition in ileus and sham groups (P < 0.05). N6-(1
      iminoethyl)-l-lysine and nimesulide decreased isoprenaline-induced inhibition in
      ileus groups 12 h, 1, and 7 days, and in sham controls 7 days postoperatively (P
      < 0.05). Propranolol prevented isoprenaline effects in all groups (P < 0.05).
      CONCLUSIONS & INFERENCES: Inhibitory effects of isoprenaline on contractile
      activity were decreased for 7 days postoperatively. Changes in beta-adrenergic
      neurotransmission do not induce postoperative ileus and appear to be caused by
      anesthesia and laparotomy rather than bowel manipulation.

PMID- 23009555
TI  - A novel method to quantify IRDye800CW fluorescent antibody probes ex vivo in
      tissue distribution studies.
AB  - BACKGROUND: We describe a new method for biodistribution studies with IRDye800CW
      fluorescent antibody probes. This method allows the quantification of the
      IRDye800CW fluorescent tracer in percentage of injected dose per gram of tissue
      (% ID/g), and it is herein compared to the generally used reference method that
      makes use of radioactivity. METHODS: Cetuximab was conjugated to both the near
      infrared fluorophore IRDye800CW and/or the positron emitter 89-zirconium, which
      was injected in nude mice bearing A431 human tumor xenografts. Positron emission
      tomography (PET) and optical imaging were performed 24 h post-injection (p.i.).
      For the biodistribution study, organs and tumors were collected 24 h p.i., and
      each of these was halved. One half was used for the determination of probe uptake
      by radioactivity measurement. The other half was homogenized, and the content of
      the fluorescent probe was determined by extrapolation from a calibration curve
      made with the injected probe. RESULTS: Tumors were clearly visualized with both
      modalities, and the calculated tumor-to-normal tissue ratios were very similar
      for optical and PET imaging: 3.31 +/- 1.09 and 3.15 +/- 0.99, respectively.
      Although some variations were observed in ex vivo analyses, tumor uptake was
      within the same range for IRDye800CW and gamma ray quantification: 15.07 +/-
      3.66% ID/g and 13.92 +/- 2.59% ID/g, respectively. CONCLUSIONS: The novel method
      for quantification of the optical tracer IRDye800CW gives similar results as the
      reference method of gamma ray quantification. This new method is considered very
      useful in the context of the preclinical development of IRDye800CW fluorescent
      probes for optical molecular imaging, likely contributing to the selection of
      lead compounds that are the most promising for clinical translation.

PMID- 23009556
TI  - Glycated haemoglobin and the risk of cardiovascular disease, diabetes and all
      cause mortality in the Copenhagen City Heart Study.
AB  - OBJECTIVE: Individuals with diabetes mellitus (DM) have a considerably elevated
      risk of developing serious health problems including cardiovascular disease
      (CVD). Long-term elevated levels of blood glucose in nondiabetic individuals may
      also be associated with increased risk of CVD. The aim of this study was to
      investigate the relationships between glycated haemoglobin A(1c)  (HbA(1c) ) and
      CVD, DM and all-cause mortality. SUBJECTS AND DESIGN: The Copenhagen City Heart
      Study is a prospective study of individuals from the Danish general population.
      The cohort was followed for 10 years via national registers with respect to
      incident CVD, DM and all-cause mortality. Follow-up was 100% complete. RESULTS: A
      total of 5127 subjects were included, of whom 597 had DM. In the nondiabetic
      population, HbA(1c)  was significantly associated with incident CVD events in
      both univariate [hazard ratio (HR) 1.38, 95% CI 1.11-1.71] and multivariate
      analyses (HR 1.31, 95% CI 1.05-1.64). In the nondiabetic population, increased
      levels of HbA(1c)  were correlated with developing DM. There was a threefold
      increase in risk of incident DM per unit increase in HbA(1c)  with a univariate
      HR of 3.83 (95% CI 1.96-7.51). This relationship was essentially unchanged after
      multivariate adjustments (HR 4.19, 95% CI 2.01-8.71). Furthermore, we found that
      net reclassification improvement for diagnosed DM and CVD was significantly
      improved with the addition of HbA(1c)  in the analyses. Although not
      statistically significant, we found a strong trend towards an association between
      HbA(1c)  and all-cause mortality (HR 1.21, 95% CI 0.99-1.47). We did not find the
      same associations amongst the population with DM. CONCLUSION: In the Danish
      general population, HbA(1c)  was strongly associated with CVD in individuals
      without DM.

PMID- 23009557
TI  - 2D solid-state NMR analysis of inclusion in drug-cyclodextrin complexes.
AB  - The solubility of drug molecules can often be improved through preparation and
      delivery of cyclodextrin (CD) inclusion complexes. These drug-oligosaccharide
      complexes can be prepared in solution and converted to the solid state via
      methods such as lyophilization and spray-drying, or they can be prepared directly
      from solids by a variety of methods. The development of drug-CD complexes as
      solids allows for potential advantages in dosage form design, such as the
      preparation of layered formulations, and it also can yield improvements in
      chemical and physical stability. 2D solid-state NMR (SSNMR) methods provide a
      direct way to probe drug-CD interactions in solid complexes through dipolar
      interactions between nuclei within the drug and CD molecules. In this study, 2D
      heteronuclear and homonuclear correlation SSNMR experiments involving (1)H,
      (13)C, (19)F, and (31)P nuclei are used to demonstrate the inclusion of drug
      within the CD cavity in a variety of powder samples. To illustrate the general
      applicability of the SSNMR approach presented, examples are shown for the drugs
      diflunisal, adefovir dipivoxil, voriconazole, dexamethasone, and prednisolone in
      complexes with alpha-CD, beta-CD, and sulfobutylether-substituted beta-CD. The
      quantitative analysis of included and free drug fractions in a solid drug-CD
      complex using SSNMR is also demonstrated. On the basis of these results, general
      approaches to the characterization of these materials using SSNMR are proposed.

PMID- 23009558
TI  - Insulin analogues dosing and costs - comparing real-life daily doses of insulin
      detemir and insulin glargine in type 2 diabetes patients.
AB  - BACKGROUND: The uncertainties regarding dose similarities between basal long
      acting insulin analogues remain. Recent real-world studies indicate dose
      similarities between insulin detemir and insulin glargine, but further studies
      are still warranted.The aim of this study was to compare real-life daily doses of
      insulin detemir and insulin glargine in type 2 diabetes patients when
      administered once daily. METHODS: We analysed 536 patient cases from general
      practice (63%) and endocrinological outpatient clinics (37%). A self-administered
      questionnaire completed by the treating physician was used to obtain data on
      patient characteristics (gender, age, weight, height, latest HbA1c-value), daily
      doses, administration of and number of years treated with insulin detemir and
      insulin glargine, concomitant insulin use and use of non-insulin anti-diabetic
      medication. Both bivariate analyses and multivariate regression analyses were
      applied to examine whether there were differences in the daily doses of insulin
      detemir and insulin glargine. RESULTS: There was no significant difference in the
      mean daily doses of insulin detemir (0.414 U/kg) and insulin glargine (0.416
      U/kg) (p = 0.4341). In multivariate regression analyses, age and BMI had a
      significant influence on daily insulin dose with the dose increasing 0.003 U/kg
      (p = 0.0375) and 0.008 U/kg (p = 0.0003) with every 1 increment in age and BMI,
      respectively. CONCLUSIONS: Dose similarities between insulin detemir and insulin
      glargine were seen in type 2 diabetes patients when administered once daily.
      Thus, the use of insulin detemir and insulin glargine is not associated with
      different medical costs if the price and treating algorithm are similar.

PMID- 23009559
TI  - Pure primary squamous cell carcinoma of the breast presenting as an intracystic
      tumor.

PMID- 23009560
TI  - Body work in assisted conception: exploring public and private settings.
AB  - Body work has been foregrounded in recent sociological writings on health and
      social care, particularly the emotional labour of patient care. In this article I
      explore the social and emotional dimensions of body work in assisted conception
      in private and public National Health Service (NHS) clinics. Drawing on an
      ethnographic study, I explore how tensions around bodily attributes, treatment
      costs, clinic performance and the extent of consumer sovereignty were managed in
      decisions about who to treat and in what manner. In NHS settings, body work
      involved efforts to standardise and constrain bodies in line with an ethics of
      justice that included the co-construction of protocols and performance
      measurement and a strong emphasis upon teamwork and influencing the behaviour of
      the sector as a whole. In contrast, body work in private settings was more
      overtly organised around an ethos of individual consumption that emphasised
      bespoke treatment together with an active critique of the regulator, based on a
      strong entrepreneurial ethos. Emotional labour in private settings was also more
      overt. I conclude by exploring the implications of my analysis for the study of
      assisted conception, the sociology of body work and the further marketisation and
      deregulation of medicine. 

PMID- 23009561
TI  - ncRNAclassifier: a tool for detection and classification of transposable element
      sequences in RNA hairpins.
AB  - BACKGROUND: Inverted repeat genes encode precursor RNAs characterized by hairpin
      structures. These RNA hairpins are then metabolized by biosynthetic pathways to
      produce functional small RNAs. In eukaryotic genomes, short non-autonomous
      transposable elements can have similar size and hairpin structures as non-coding
      precursor RNAs. This resemblance leads to problems annotating small RNAs.
      RESULTS: We mapped all microRNA precursors from miRBASE to several genomes and
      studied the repetition and dispersion of the corresponding loci. We then searched
      for repetitive elements overlapping these loci. We developed an automatic method
      called ncRNAclassifier to classify pre-ncRNAs according to their relationship
      with transposable elements (TEs). We showed that there is a correlation between
      the number of scattered occurrences of ncRNA precursor candidates and the
      presence of TEs. We applied ncRNAclassifier on six chordate genomes and report
      our findings. Among the 1,426 human and 721 mouse pre-miRNAs of miRBase, we
      identified 235 and 68 mis-annotated pre-miRNAs respectively corresponding
      completely to TEs. CONCLUSIONS: We provide a tool enabling the identification of
      repetitive elements in precursor ncRNA sequences. ncRNAclassifier is available at
      http://EvryRNA.ibisc.univ-evry.fr.

PMID- 23009562
TI  - Within- and between-session reliability of the maximal voluntary knee extension
      torque and activation.
AB  - A ratio between the torque generated by maximal voluntary isometric contraction
      (MVIC) and exogenous electrical stimulus, central activation ratio (CAR), has
      been widely used to assess quadriceps function. To date, no data exist regarding
      between-session reliability of this measurement. Thirteen neurologically sound
      volunteers underwent three testing sessions (three trials per session) with 48
      hours between-session. Subjects performed MVICs of the quadriceps with the knee
      locked at 90 degrees  flexion and the hip at 85 degrees . Once the MVIC reached a
      plateau, an electrical stimulation from superimposed burst technique (SIB: 125 V
      with peak output current 450 mA) was manually delivered and transmitted directly
      to the quadriceps via stimulating electrodes. CAR was calculated by using the
      following equation: CAR = MVIC torque/MVIC + SIB torque. Intraclass correlation
      coefficients (ICC) were calculated within- (ICC((2,1))) and between-session
      (ICC((2,k))) for MVIC torques and CAR values. Our data show that quadriceps MVIC
      and CAR are very reliable both within- (ICC((2,1)) = 0.99 for MVIC; 0.94 for CAR)
      and between-measurement sessions (ICC((2,k)) = 0.92 for MVIC; 0.86 for CAR) in
      healthy young adults. For clinical research, more data of the patients with
      pathological conditions are required to ensure reproducibility of calculation of
      CAR.

PMID- 23009563
TI  - Osteoporosis and metabolic syndrome according to socio-economic status,
      contribution of PTH, vitamin D and body weight: The Canarian Osteoporosis Poverty
      Study (COPS).
AB  - BACKGROUND: Poverty is associated with a great number of diseases, but the
      prevalence of vitamin D deficiency, secondary hyperparathyroidism and the
      potential association of osteoporosis, osteoporotic fractures and metabolic
      syndrome in this situation are less well known. OBJECTIVE: To evaluate the
      associations between poverty, bone density, fragility fractures and metabolic
      syndrome in a population of southern European postmenopausal women. Also, to
      assess the potential role of vitamin D and parathyroid hormone (PTH) levels in
      these associations. METHOD: Cross-sectional study was carried out in 1 250
      postmenopausal Caucasian Spanish women. The socio-economic status of the
      participants was determined after a personal interview, according to the criteria
      of the Spanish Institute of Statistics. Participants were divided into two socio
      economic levels: low (poverty) and medium or high socioeconomic level. The study
      protocol included a health questionnaire, a complete physical examination,
      lateral radiograph of the dorsal and lumbar spine and measurement of bone mineral
      density (BMD) at the lumbar spine (L2-L4) and proximal femur. Fasting blood was
      obtained to measure 25-hydroxy-vitamin D (25-OHD), intact PTH and selected
      biochemical variables. RESULTS: Low socio-economic status was associated with 25
      OHD insufficiency, higher values of PTH, higher body weight and body mass index
      (BMI), lower values of BMD at the lumbar spine and a higher prevalence of
      fragility fractures, both vertebral and nonvertebral. Poverty was also associated
      with higher prevalence of metabolic syndrome, but this association was driven
      mainly by the higher BMI and not by poverty itself. Both vitamin D insufficiency
      and elevated PTH were consistently related to poverty and osteoporotic fractures.
      CONCLUSIONS: Poor postmenopausal women in southern Europe have a high prevalence
      of metabolic syndrome and osteoporotic fractures. Poverty was associated with
      higher BMI and metabolic syndrome on the one hand and, on the other, with 25OHD
      insufficiency, higher PTH levels and osteoporosis. 25OHD insufficiency and/or
      secondary hyperparathyroidism do not have a significant influence on the presence
      of metabolic syndrome in this population.

PMID- 23009564
TI  - Effects of juvenile court exposure on crime in young adulthood.
AB  - BACKGROUND: The juvenile justice system's interventions are expected to help
      reduce recidivism. However, previous studies suggest that official processing in
      juvenile court fails to reduce adolescents' criminal behavior in the following
      year. Longer term effects have not yet been investigated with a rigorous method.
      This study used propensity score matching to assess the impact of juvenile court
      processing into young adulthood. METHOD: Participants were part of a prospective
      longitudinal study of 1,037 boys from low- socioeconomic areas of Montreal,
      followed from ages 6-25 years. During their adolescence, 176 participants were
      processed in juvenile court, whereas 225 were arrested, but not sent to court.
      Propensity score matching was used to balance the group of participants exposed
      to juvenile court and the unexposed comparison group on 14 preadolescent child,
      family and peer characteristics. The two groups were compared on their official
      adult criminal outcomes. RESULTS: The risk of conviction for an adult offence was
      50.0% for court-processed participants compared with 24.3% for their matched
      counterparts, OR = 3.13, 95% CI = 1.80-5.44. Court-processed participants
      committed an average of 0.39 violent crimes, compared with 0.15 for their matched
      counterparts; Poisson model IRR = 2.60, 95% CI = 1.39-4.87. They also committed
      an average of 2.38 nonviolent crimes, compared to 1.30 for their matched
      counterparts, IRR = 1.87, 95% CI = 1.19-2.93. CONCLUSIONS: Rather than decreasing
      recidivism, juvenile court intervention increased both violent and nonviolent
      future crimes. Along with previous studies, this study highlights a pressing need
      for more research and knowledge transfer about effective interventions to reduce
      recidivism among youths who commit crime.

PMID- 23009565
TI  - NF-kappaB activation: Tax sumoylation is out, but what about Tax ubiquitination?
AB  - Activation of the NF-kappaB transcription factors by the viral protein Tax plays
      a vital role in the pathogenesis of diseases associated with human T-cell
      lymphotropic virus type I (HTLV-I). The Tax oncoprotein undergoes constitutive
      K63-linked ubiquitination and sumoylation; however, the roles and molecular
      mechanisms of these post-translational modifications in Tax-mediated NF-kappaB
      activation are being debated. Here, we discuss our current understanding of Tax
      activation of NF-kappaB, with a focus on the controversies and the challenges
      that we are facing.

PMID- 23009566
TI  - Biomolecular analyses of starch and starch granule proteins in the high-amylose
      rice mutant Goami 2.
AB  - Elevated proportions of amylose in cereals are commonly associated with either
      the loss of starch branching or starch synthase activity. Goami 2 is a high
      amylose mutant of the temperate japonica rice variety Ilpumbyeo. Genotyping
      revealed that Goami 2 and Ilpumbyeo carry the same alleles for starch synthase
      IIa and granule-bound starch synthase I genes. Analyses of granule-bound proteins
      revealed that SSI and SSIIa accumulate inside the mature starch granules of Goami
      2, which is similar to the amylose extender mutant IR36ae. However, unlike the
      amylose extender mutants, SBEIIb was still detectable inside the starch granules
      of Goami 2. Detection of SBEIIb after protein fractionation revealed that most of
      the SBEIIb in Goami 2 accumulates inside the starch granules, whereas most of it
      accumulates at the granule surface in Ilpumbyeo. Exhaustive mass spectrometric
      characterisations of granule-bound proteins failed to detect any peptide sequence
      mutation or major post-translational modifications in Goami 2. Moreover, the
      signal peptide was found to be cleaved normally from the precursor protein, and
      there is no apparent N-linked glycosylation. Finally, no difference was found in
      the SBEIIb structural gene sequence of Goami 2 compared with Ilpumbyeo. In
      contrast, a G-to-A mutation was detected in the SBEIIb gene of IR36ae located at
      the splice site between exon and intron 11, which could potentially introduce a
      premature stop codon and produce a truncated form of SBEIIb. It is suggested that
      the mutation responsible for producing high amylose in Goami 2 is not due to a
      defect in SBEIIb gene as was observed in IR36ae, even though it produces a
      phenotype analogous to the amylose extender mutation. Understanding the molecular
      genetic basis of this mutation will be important in identifying novel targets for
      increasing amylose and resistant starch contents in rice and other cereals.

PMID- 23009567
TI  - Post-partum blues among Korean mothers: a structural equation modelling approach.
AB  - The objective of this study was to propose the post-partum blues (PPB) model and
      to estimate the effects of self-esteem, social support, antenatal depression, and
      stressful events during pregnancy on PPB. Data were collected from 249 women post
      partum during their stay in the maternity units of three hospitals in Korea using
      a self-administered questionnaire. A structural equation modelling approach using
      the Analysis of Moments Structure program was used to identify the direct and
      indirect effects of the variables on PPB. The full model had a good fit and
      accounted for 70.3% of the variance of PPB. Antenatal depression and stressful
      events during pregnancy had strong direct effects on PPB. Household income showed
      indirect effects on PPB via self-esteem and antenatal depression. Social support
      indirectly affected PPB via self-esteem, antenatal depression, and stressful
      events during pregnancy.

PMID- 23009568
TI  - Correction to Synthesis of Heterocycles via Pd-Ligand Controlled Cyclization of 2
      Chloro-N-(2-vinyl)aniline: Preparation of Carbazoles, Indoles, Dibenzazepines,
      and Acridines.

PMID- 23009569
TI  - Economic evaluations conducted for assessment of genetic testing technologies: a
      systematic review.
AB  - AIMS: To systematically review the methods used in economic evaluations (EEs)
      included in health technology assessments (HTAs) of genetic testing technologies
      (GTTs). METHODS: A systematic search using bibliographic databases and gray
      literature was undertaken to identify HTA reports on GTTs that included EEs in
      addition to clinical effectiveness results. Studies were reviewed in terms of
      methodology and reporting. RESULTS: Of 361 identified citations, 15 HTAs
      consisting of 11 model-based and 4 trial-based EEs were included, more than 50%
      of which had moderate-to-low-quality scores mainly due to not reporting
      information on basic elements of a standard EE and inadequate management of
      uncertainty. Cost-effectiveness analysis accounted for 62% of studies.
      Approximately 66% of the studies adopted a third-party payer perspective, and 46%
      used a lifelong time horizon. The majority of studies exclusively included
      technical costs of testing (100%) and therapeutic or preventive interventions
      (60%). The most frequent variables tested in sensitivity analysis included costs
      (66%), effects (50%), and transition probabilities (58%). CONCLUSIONS: We found
      several methodological challenges in the reviewed EEs, including identification
      of a proper analytical perspective, inclusion of wider range of outcomes and
      costs, allowing for long-term medical and nonmedical impacts of genetic tests,
      and sufficient management of uncertainty. These issues should be carefully
      considered in future EEs of GTTs.

PMID- 23009570
TI  - Association between the CTLA-4 +49A/G polymorphism and type 1 diabetes: a meta
      analysis.
AB  - BACKGROUND: +49A/G polymorphism of the cytotoxic T-lymphocyte-associated antigen
      4 gene (CTLA-4) has been associated with type 1 diabetes (T1D). However, results
      were inconsistent. The aim of this study was to quantitatively summarize the
      evidence for CTLA-4 +49A/G polymorphism and T1D. METHODS: Electronic search of
      PubMed was conducted to select studies. Case-control studies containing available
      genotype frequencies of CTLA-4 +49 were chosen, and the odds ratio (OR) with 95%
      confidence interval (CI) was used to assess the strength of this association.
      RESULTS: 49 case-control studies, including 8976 cases and 11012 controls, were
      identified. 8 studies were eliminated from the total 49 studies because of p<0.05
      (p value for Hardy-Weinberg equilibrium in the control group) in these studies,
      which induce significant publication bias. The overall results suggested that the
      variant genotypes were highly associated (p<0.01) with T1D risk in all genetic
      models (additive model: OR 1.345, 95% CI 1.249-1.448, p<0.001; recessive model:
      OR 1.530, 95% CI 1.370-1.708, p<0.001; dominant model: OR 1.409, 95% CI 1.263
      1.572 p<0.001). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian),
      the results were positive. CONCLUSION: This meta-analysis suggests that the CTLA
      4 +49A/G polymorphism is highly associated (p<0.01) with increased risk of T1D,
      especially in Caucasians and Asians. To validate this association, further
      studies with more participants worldwide are needed to examine associations
      between this polymorphism and T1D. Otherwise, we found that the studies of
      Africans are rare. More studies in Africans are needed especially.

PMID- 23009571
TI  - ABL kinase domain mutations in patients with chronic myeloid leukemia in Jordan.
AB  - Mutations of the BCR-ABL tyrosine kinase domain constitute a major cause of
      resistance to tyrosine kinase inhibitors in patients with chronic myelogenous
      leukemia (CML). In this study, we analyzed peripheral blood samples from 185
      Jordanian CML patients for ABL mutations, who were on imatinib for a minimum of 6
      months regardless of their disease status and over a period of 5 years. Mutations
      were detected by nested RT-polymerase chain reaction, followed by direct
      sequencing of the ABL kinase domain. Twelve different point mutations were
      detected 25 times in 21 patients. The resultant mutations were as follows: four
      patients have T315I, three of each of the following: L248V, F317L, and G250E, two
      of each of the following: H396R, M244V, and T277A, and one of each of the
      following: F311I, M318T, Q252H, F359A, F359I, and Y326H. After patient follow-up,
      the mutation had disappeared in 12 patients; 3 patients died; 3 patients were not
      retested; and 3 patients had persistent mutation. The finding of our study is in
      line with what has been described in the literature. Detecting ABL mutations in
      chronic phase may lead to positive outcome by modifying treatment.

PMID- 23009572
TI  - beta-catenin and K-ras mutations and RASSF1A promoter methylation in Taiwanese
      colorectal cancer patients.
AB  - AIMS: The purpose of this study was to investigate the associations of beta
      catenin mutations, K-ras mutations, methylations of the RASSF1A promoter, and the
      survival of Taiwanese colorectal cancer (CRC) subjects who received 5
      fluorouracil (5-FU) adjuvant chemotherapy. RESULTS: The complete coding region of
      the K-ras gene and exon 3 and exon 4 of the beta-catenin gene isolated from tumor
      tissues and adjacent normal colon tissues from 117 CRC subjects were sequenced,
      respectively. Methylations in the RASSF1A promoter region were also investigated.
      Various characteristics of the 117 subjects were recorded and used in the Cox
      proportional-hazard model analyses. Three missense mutations, one nonsense
      mutation, and one deletion were identified in the beta-catenin gene. A 2 bp
      deletion was identified in the K-ras gene. We found that the frequencies of
      mutations in the beta-catenin and K-ras genes were less pronounced in Taiwanese
      CRC subjects as compared with other populations. Methylations in the RASSF1A
      promoter region were detected in 73.5% (n=86/117) of the subjects, which was
      higher than in other studies. Methylations in the RASSF1A promoter have no
      significant effect on hazards for all CRC deaths caused in Taiwanese CRC
      patients. No interaction between 5-FU adjuvant chemotherapy and methylations of
      the RASSF1A promoter was observed. CONCLUSIONS: The mutation frequencies of beta
      catenin and K-ras genes in Taiwanese CRC patients are very low, which may suggest
      that they are not the dominant factors for CRC occurrence and prognosis in
      Taiwanese CRC patients. Methylation of RASSF1A promoter is independent of the
      prognosis for Taiwanese CRC patients. Taiwanese subjects differ from subjects of
      other populations with regard to beta-catenin, K-ras, and RASSF1A presentations
      for CRC.

PMID- 23009573
TI  - Listening to music during cystoscopy decreases anxiety, pain, and dissatisfaction
      in patients: a pilot randomized controlled trial.
AB  - PURPOSE: To determine whether listening to music during cystoscopy decreases
      anxiety, pain, and dissatisfaction among patients and results in a more
      comfortable and better-tolerated procedure. MATERIALS AND METHODS: Seventy male
      patients who underwent rigid cystoscopy between May 2011 and December 2011 were
      randomized into the following: no music (Group I, n=35) or classical music during
      procedure (Group II, n=35). Before cystoscopy, lidocaine gel was instilled in the
      urethra, and both groups viewed their procedures on a video monitor. Anxiety
      levels were quantified according to the State-Trait Anxiety Inventory. A visual
      analog scale (0-10) was used for a self-assessment of satisfaction, discomfort,
      and willingness among patients to repeat the cystoscopy. RESULTS: Demographic
      characteristics, mean age, procedure duration, and procedure indications were
      statistically similar between the two groups. The mean anxiety level and mean
      pain score of Group II were significantly lower than those of Group I (p<0.001
      for both). Group II also carried a significant greater mean satisfaction score
      compared with Group I (p<0.001). Statistically significant differences were
      detected between groups in the postprocedural pulse rate and the systolic blood
      pressure (p=0.012 and p=0.008, respectively), whereas preprocedure pulse rate and
      systolic blood pressure were similar. CONCLUSIONS: Listening to music during
      rigid cystoscopy significantly reduces feelings of pain, discomfort, and
      dissatisfaction. Music can serve as a simple, inexpensive, and effective adjunct
      to sedation during cystoscopy. We recommend the application of music during rigid
      cystoscopy for clinical use.

PMID- 23009574
TI  - Evidence of Oral diseases' impact.

PMID- 23009575
TI  - MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated
      with interferon beta along two-year follow-up.
AB  - BACKGROUND: In previous studies we found that MHC2TA +1614 genotype frequency was
      very different when MS patients with and without human herpesvirus 6 (HHV-6) in
      serum samples were compared; a different clinical behavior was also described.
      The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients
      was influenced by interferon beta (IFN-beta) treatment. 2. To study MHC2TA
      expression in MS patients with and without minor allele C. 3. To analyze the
      relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients.
      METHODS: Blood and serum samples of 154 MS patients were collected in five
      programmed visits: basal (prior to beginning IFN-beta treatment), six, twelve,
      eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were
      evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs) against
      IFN-beta were analyzed by the cytopathic effect assay. RESULTS: We found that
      MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active
      infection at the basal visit (without treatment) than in those MS patients
      without HHV-6 active infection at the basal visit (p = 0.012); in all the
      positive samples we only found variant A. Furthermore, 58/99 (58.6%) MS patients
      without HHV-6 along the five programmed visits and an increase of MHC2TA
      expression after two-years of IFN-beta treatment were clinical responders vs.
      5/21 (23.8%) among those MS patients with HHV-6 and a decrease of MHC2TA mRNA
      levels along the two-years with IFN-beta treatment (p = 0.004); no differences
      were found between patients with and without NAbs. CONCLUSIONS: MHC2TA mRNA
      levels could be decreased by the active replication of HHV-6; the absence of HHV
      6 in serum and the increase of MHC2TA expression could be further studied as
      markers of good clinical response to IFN-beta treatment.

PMID- 23009576
TI  - Melatonin decreases duodenal epithelial paracellular permeability via a nicotinic
      receptor-dependent pathway in rats in vivo.
AB  - Intestinal epithelial intercellular tight junctions (TJs) provide a rate-limiting
      barrier restricting passive transepithelial movement of solutes. TJs are highly
      dynamic areas, and their permeability is changed in response to various stimuli.
      Defects in the intestinal epithelial TJ barrier may contribute to intestinal
      inflammation or leaky gut. The gastrointestinal tract may be the largest
      extrapineal source of endogenous melatonin. Melatonin released from the duodenal
      mucosa is a potent stimulant of duodenal mucosal bicarbonate secretion (DBS). The
      aim of this study was to elucidate the role of melatonin in regulating duodenal
      mucosal barrier functions, including mucosal permeability, DBS, net fluid flux,
      and duodenal motor activity, in the living animal. Rats were anesthetized with
      thiobarbiturate, and a ~30-mm segment of the proximal duodenum with an intact
      blood supply was perfused in situ. Melatonin and the selective melatonin receptor
      antagonist luzindole were perfused luminally or given intravenously. Effects on
      permeability (blood-to-lumen clearance of (51)Cr-EDTA), DBS, mucosal net fluid
      flux, and duodenal motility were monitored. Luminal melatonin caused a rapid
      decrease in paracellular permeability and an increase in DBS, but had no effect
      on duodenal motor activity or net fluid flux. Luzindole did not influence any of
      the basal parameters studied, but significantly inhibited the effects of
      melatonin. The nonselective and noncompetitive nicotinic acetylcholine receptor
      antagonist mecamylamine abolished the effect of melatonin on duodenal
      permeability and reduced that on DBS. In conclusion, these findings provide
      evidence that melatonin significantly decreases duodenal mucosal paracellular
      permeability and increases DBS. The data support the important role of melatonin
      in the neurohumoral regulation of duodenal mucosal barrier.

PMID- 23009577
TI  - Chloramine-induced anaphylaxis while showering: a case report.
AB  - INTRODUCTION: Sodium-N-chlorine-p-toluene sulfonamide, commonly known as
      chloramine-T, is a derivative of chlorine which is widely used as a disinfectant.
      For many years, chloramine-T has been described as a cause of immediate-type
      hypersensitivity, especially with regard to asthma and rhinitis, and as a cause
      of occupational dermatoses in cleaning personnel in hospitals, although no
      anaphylactic reaction has yet been reported. Hence, to the best of our knowledge
      we present the first case of anaphylaxis to chloramine-T with evidence of
      specific immunoglobulin E antibodies. CASE PRESENTATION: We describe the case of
      a 25-year-old Caucasian woman who was in good health and with a negative history
      for atopy, including no respiratory symptoms of rhinitis or asthma, and with no
      professional exposure to chloramine-T. She, while showering, applied a chloramine
      T solution to a skin area with folliculitis on her leg, and within a few minutes
      developed generalized urticaria and angioedema, followed by vomiting and collapse
      with loss of consciousness. A skin prick test with a chloramine-T solution at
      10mg/mL concentration was positive, and specific immunoglobulin E to chloramine-T
      was quantified at a value of 2.9 optical density as measured by the enzyme
      allergosorbent test technique. CONCLUSION: The strict cause-effect relationship
      and the results of the skin test and the in vitro test make certain the causative
      role of chloramine-T in this case of anaphylaxis. This suggests that chloramine
      T, based on its wide use as a disinfectant, should be considered a possible cause
      in anaphylaxis of unknown origin.

PMID- 23009578
TI  - Capture and dimethyl labeling of glycopeptides on hydrazide beads for
      quantitative glycoproteomics analysis.
AB  - Incorporation of isotopic tag onto peptides via chemical labeling is a popular
      approach for quantitative proteomics. Chemical labeling via solution based
      methods usually lead to a tedious process and sample loss because several sample
      preparation steps including buffer exchange and desalting are performed. In this
      study, a solid phase based labeling approach by integration of glycopeptide
      enrichment and stable isotope labeling on hydrazide beads was developed for
      relative quantification of protein glycosylation, by which enrichment, washing,
      labeling, and release of the glycopeptides were all performed on the hydrazide
      beads sequentially. This approach was proved to be accurate in quantitative
      glycoproteome analysis and have good linearity range with 2 orders of magnitude
      for quantification of glycopeptides. Compared with dimethyl labeling
      conventionally performed in solution, the developed approach has better
      enrichment recovery (10-330% improvement) and high detection sensitivity in which
      42% of annotated glycosites (vs 26%) still can be quantified using only 10 MUg of
      four standard glycoprotein mixtures and 400 MUg of bovine serum album
      interference as starting sample. The applicability of the approach for
      quantitative glycopeptide profiling was also explored by differential analysis of
      glycoproteome between human normal serum and liver cancer serum.

PMID- 23009579
TI  - Validation study of the prototype of a disease-specific index measure for health
      related quality of life in dementia.
AB  - BACKGROUND: Index measures for health-related quality of life (HRQoL) quantify
      the desirability (utility) of a certain health state. The commonly used generic
      index measure, e.g. EuroQol: EQ-5D, may underestimate relevant areas of specific
      diseases, resulting in lower validity. Disease-specific index measures on the
      other hand combine disease-specificity and quantification of perceived quality on
      several health domains of a certain disease into one single figure. These
      instruments have been developed for several diseases, but a dementia-specific
      HRQoL index instrument was not yet available. Facing the increasing individual
      and societal burden of dementia, specific HRQoL values with metric
      characteristics are especially useful because they will provide vital information
      for health outcome research and economic evaluations. AIMS OF THE STUDY: To
      develop and validate the prototype of a dementia-specific HRQoL index measure:
      Dementia Quality of life Instrument (DQI), as the first step towards valuation of
      the dementia health state. METHODS: For development of the DQI we created a
      conceptual framework based on a review of the literature, qualitative interviews
      with people with dementia and their carers, expert opinion and team discussion.
      To assess validity we undertook a survey under 241 dementia professionals.
      Measurements consisted of ranking (1-5) and rating (1-10) of 5 dementia-specific
      DQI domains (memory, orientation, independence, social activities and mood) and
      simultaneously rating of 9 DQI-derived health states on a visual analogue scale
      (VAS). We also performed a cross-sectional study in a large sample of people with
      very mild to moderate dementia and their caregivers (N=145) to assess feasibility
      and concurrent validity. In addition, caregivers valued 10 DQI and 10 EQ-5D + C
      derived health states of the patient simultaneously on the same VAS. SETTING:
      outpatient clinics, nursing homes and patient residences. RESULTS: All
      professionals judged the selected DQI domains to be relevant. Differences in
      ranking and rating behaviors were small. Mood was ranked (>= 3.3) and rated (>=
      8.2) as most, orientation as least important (rank <= 2.6, value 7.5) health
      domain for dementia. For the validation part of this study the completion rates
      for all domains were above 98% for patients and 100% for caregivers on patients.
      A priori hypothesized DQI versus QOL-AD correlations that were significant in
      both patients and caregivers were: memory/memory, orientation/memory,
      independence/physical health, social activities/energy and mood/mood.
      Patient/caregiver inter-rater agreement was low (K <0.2) for memory/independence,
      fair (K 0.2-0.4) for orientation/mood, and moderate (K 0.4-0.6) for social
      activities. Concurrent validity of the DQI with the EQ-5D +C was moderate. The
      fact that most of the correlations between the domains of these two instruments
      were low (<= 0.40) showed that both instruments measure different elements of
      health status. As expected, modest correlations (>= 0.40) were observed between
      corresponding domains of the two instruments. CONCLUSIONS: Professionals judged
      all domains as relevant. The DQI prototype proved valid and feasible for patients
      and caregivers and is appropriate for very mild to moderate dementia. The
      differences in concurrent correlations with generic health status instruments
      imply that the dementia-specific DQI health domains indeed provide different
      information. The finding that patient HRQoL measured with the DQI was lower
      supports this notion. The new DQI shows comparable psychometric properties to the
      best available dementia-specific (QOL-AD) and generic (EQ-5D +C) measures.
      Further research is needed to generate values in the general population for each
      of the possible DQI states and to derive an algorithm that converts the 5
      separate DQI domain scores into one single DQI Index score. Introducing the DQI
      Index will advance dementia-related HRQoL measurement by overcoming the
      shortcomings of generic and non-index instruments. This will allow more
      unequivocal interpretation of subjective dementia HRQoL states in dementia
      research.

PMID- 23009580
TI  - Renal and hematological toxicity in patients of neuroendocrine tumors after
      peptide receptor radionuclide therapy with 177Lu-DOTATATE.
AB  - PURPOSE: Peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE is an
      efficient new treatment option in patients with neuroendocrine tumors (NETs),
      with low risk of toxicity. Since the kidneys are critical organs in PRRT, renal
      function is known to deteriorate after PRRT. We analyzed the decline in
      glomerular filtration rate (GFR), increase in serum creatinine (SCr), and changes
      in hemogram parameters between pretherapy and at least 6 months after last cycle
      post-therapy with (177)Lu-DOTATATE. METHODS: Forty-seven patients with NETs
      received 2-6 cycles of (177)Lu-DOTATATE, leading to a total renal radiation
      absorbed dose of 12.5 +/- 4.1 Gy. All renal dose estimates were calculated with
      the help of OLINDA/EXM software. All patients were infused with renal protective
      amino acids during the administration of the radiopharmaceuticals. In this study,
      we used GFR that was estimated by in vitro method using (99m)Tc-DTPA and SCr to
      assess renal toxicity. RESULTS: The patients were administered a mean cumulative
      activity of 20.1 +/- 6.74 GBq of (177)Lu-DOTATATE. There was a significant
      decrease in GFR from 86.8 +/- 15.4 mL/1.73 m(2)/min to 66.1 +/- 14.5 mL/1.73
      m(2)/min and rise in SCr from 0.86 +/- 0.19 mg/dL to 1.0 +/- 0.2 mg/dL with
      treatment. Patients with WHO grade 1 renal toxicity (group 2) at baseline
      demonstrated an increase in SCr that was significantly higher compared with
      patients with normal baseline creatinine levels (group 1). No serious acute or
      remote adverse events were recorded. Self-limiting serious hematological toxicity
      was observed in 2 patients. CONCLUSIONS: The decline in renal function as
      measured by in vitro GFR tends to be of greater magnitude in patients with
      baseline impaired renal function than in patients with preserved renal function
      after PRRT. Hematologic toxicity is relatively rare and can be managed
      conservatively when encountered.

PMID- 23009581
TI  - Clinical investigations on the spinal osteoblastic metastasis treated by
      combination of percutaneous vertebroplasty and (125)I seeds implantation versus
      radiotherapy.
AB  - To investigate the clinical efficacy of combining digital subtraction angiography
      guided percutaneous vertebroplasty (PVP) and (125)I seeds implantation for the
      treatment of spinal osteoplastic metastasis. A combination of PVP and (125)I
      implantation was conducted for 50 patients with spinal osteoplastic metastasis,
      while the other 50 patients who received regular radiation therapy were used as a
      comparison. Visual analogue pain scale (VAS) and score of life quality (EORTCQLQ
      30) were determined for all the patients. Surgery was successful in 89 spinal
      segments of vertebral body in 50 patients. Each segment of vertebral body was
      injected with 1-5 mL (2.8 mL for thoracic and 3.1 mL for lumbar vertebral body on
      average) of bone cement. Postoperative X-ray and CT examination showed that all
      the patients in the PVP group achieved spinal stability. During the follow-up
      examination from 6 months to 5 years, 49 patients (98.0%) had significantly
      relieved back pain, and only 1 case (2.0%) had no obvious improvement.
      Postoperative VAS score and Karnofsky performance score (KPS) were significantly
      different from the preoperative scores (p<0.05); and compared to the regular
      treatment group, PVP combined (125)I seeds showed much better clinical efficacy
      (p<0.05). PVP is a minimally invasive treatment with easy operation and less
      complications. PVP can effectively relieve the pain, stabilize the spine, improve
      the life quality, and reduce the occurrence of paraplegia in patients with spinal
      osteoplastic metastasis. Utilization of (125)I seeds with PVP can enhance the
      clinical efficacy.

PMID- 23009582
TI  - Comparison of cell-labeling methods with 124I-FIAU and 64Cu-PTSM for cell
      tracking using chronic myelogenous leukemia cells expressing HSV1-tk and firefly
      luciferase.
AB  - Cell-tracking methods with molecular-imaging modality can monitor the
      biodistribution of cells. In this study, the direct-labeling method with 64Cu
      pyruvaldehyde-bis(N4-methylthiosemicarbazone) (64Cu-PTSM), indirect cell-labeling
      methods with herpes simplex virus type 1-thymidine kinase (HSV1-tk)-mediated 124I
      2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (124I-FIAU) were
      comparatively investigated in vitro and in vivo for tracking of human chronic
      myelogenous leukemia cells. K562-TL was established by retroviral transduction of
      the HSV1-tk and firefly luciferase gene in the K562 cell. K562-TL cells were
      labeled with 64Cu-PTSM or 124I-FIAU. Cell labeling efficiency, viability, and
      radiolabels retention were compared in vitro. The biodistribution of radiolabeled
      K562-TL cells with each radiolabel and small-animal positron emission tomography
      imaging were performed. Additionally, in vivo and ex vivo bioluminescence imaging
      (BLI) and tissue reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis were used for confirming those results. K562-TL cells were efficiently
      labeled with both radiolabels. The radiolabel retention (%) of 124I-FIAU (95.2%+/
      1.1%) was fourfold higher than 64Cu-PTSM (23.6%+/-0.7%) at 24 hours postlabeling.
      Viability of radiolabeled cells was statistically nonsignificant between 124I
      FIAU and 64Cu-PTSM. The radioactivity of each radiolabeled cells was
      predominantly accumulated in the lungs and liver at 2 hours. Both the
      radioactivity of 64Cu-PTSM- and 124I-FIAU-labeled cells was highly accumulated in
      the liver at 24 hours. However, the radioactivity of 124I-FIAU-labeled cells was
      markedly decreased from the body at 24 hours. The K562-TL cells were dominantly
      localized in the lungs and liver, which also verified by BLI and RT-PCR analysis
      at 2 and 24 hours postinjection. The 64Cu-PTSM-labeled cell-tracking method is
      more efficient than 124I-FIAU-labeled cell tracking, because of markedly decrease
      of radioactivity and fast efflux of 124I-FIAU in vivo. In spite of a high
      labeling yield and radiolabel retention of 124I-FIAU in vitro, the in vivo cell
      tracking method using 64Cu-PTSM could be a useful method to evaluate the
      distribution and targeting of various cell types, especially, stem cells and
      immune cells.

PMID- 23009583
TI  - Ferulic acid inhibits gamma radiation-induced DNA strand breaks and enhances the
      survival of mice.
AB  - Ferulic acid (FA) is a monophenolic phenylpropanoid occurring in plant products
      such as rice bran, green tea, and coffee beans. It has been shown to have
      significant antioxidant effects in many studies. In the present study, we show
      that intraperitoneal administration of FA at a dose of 50 mg/kg body weight 1
      hour prior to or immediately after whole-body gamma-irradiation of mice with 4 Gy
      results in considerable reduction in the micronuclei formation in peripheral
      blood reticulocytes. Administration of the same amount of FA immediately after 4
      Gy gamma-irradiation showed significant decrease in the amount of DNA strand
      breaks in murine peripheral blood leukocytes and bone marrow cells as examined by
      comet assay. Further, immunostaining of mouse splenic lymphocytes for phspho
      gammaH2AX was carried out, and it was observed that FA inhibits the gammaH2AX
      foci formation. Finally, the survival of mice upon 6, 8, and 10 Gy gamma-ray
      exposure was monitored. FA enhances the survival of mice by a factor of 2.5 at a
      dose of 6 Gy gamma-radiation but not at higher doses. In conclusion, FA has
      protective potential in both pre- and postirradiation exposure scenarios and
      enhances the survival of mice possibly by decreasing DNA damage as examined by
      gammaH2AX foci, micronuclei formation, and comet assay.

PMID- 23009584
TI  - The bioinformatics analysis of miRNAs signatures differentially expressed in
      HER2(+) versus HER2(-) breast cancers.
AB  - OBJECTIVE: To identify the signatures of miRNAs differentially expressed in
      HER2(+) versus HER2(-) breast cancers that accurately predict the HER2 status of
      breast cancer, and to provide further insight into breast cancer therapy.
      METHODS: By the methods of literature search, aberrant expressed miRNAs were
      collected. By target prediction algorithm of TargetScan and PicTar and the data
      enrichment analysis, target gene sets of miRNAs differentially expressed in
      HER2(+) versus HER2(-) breast cancers were built. Then, using the Database for
      Annotation, Visualization, and Integrated Discovery (DAVID) database, the
      function modules of Gene Ontology categories and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) and BIOCARTA pathway, biological functions and signaling pathways
      that are probably regulated by miRNAs, were analyzed. RESULTS: We got five sets
      of miRNAs expressed in different HER2 status of breast cancers finally. The five
      sets of data contain 22; 32; 3; 38; and 62 miRNAs, respectively. After miRNAs
      target prediction and data enrichment, 5,734; 22,409; 1,142; 22,293; and 43,460
      target genes of five miRNA sets were collected. Gene ontology analysis found
      these genes may be involved in transcription, protein transport, angiogenesis,
      and apoptosis. Moreover, certain KEGG and BIOCARTA signaling pathways related
      toHER2 status were found. CONCLUSION: Using TargetScan and PicTar for data
      enrichment, and DAVID database, Gene Ontology categories, KEGG and BIOCARTA
      pathway for analysis of miRNAs different expression, we conducted a new method
      for biological interpretation of miRNA profiling data in HER2(+) versus HER2(-)
      breast cancers. It may improve understanding the regulatory roles of miRNAs in
      different molecular subtypes of breast cancers. Therefore, it is beneficial to
      improve the accuracy of experimental efforts to breast cancer and potential
      therapeutic targets.

PMID- 23009585
TI  - Availability of yttrium-90 from strontium-90: a nuclear medicine perspective.
AB  - Yttrium-90 (T(1/2) 64.1 hours, E(betamax)=2.28 MeV) is a pure beta- particle
      emitting radionuclide with well-established applications in targeted therapy.
      There are several advantages of 90Y as a therapeutic radionuclide. It has a
      suitable physical half-life (~64 hours) and decays to a stable daughter product
      90Zr by emission of high-energy beta- particles. Yttrium has a relatively simple
      chemistry and its suitability for forming complexes with a variety of chelating
      agents is well established. The 90Sr/90Y generator is an ideal source for the
      long-term continuous availability of no-carrier-added 90Y suitable for the
      preparation of radiopharmaceuticals for radionuclide therapy. The parent
      radionuclide 90Sr, which is a long-lived fission product, is available in large
      quantities from spent fuel. Several useful technologies have been developed for
      the preparation of 90Sr/90Y generators. There are several well-established
      radiopharmaceuticals based on monoclonal antibodies, peptides, and particulates
      labeled with 90Y, that are in regular use for the treatment of some forms of
      primary cancers and arthritis. At present, there are no generators for the
      elution of 90Y that can be set up in a hospital radiopharmacy. The radionuclide
      is procured from manufacturers and the radiopharmaceuticals are formulated on
      site. This article reviews the development of 90Sr/90Y generator and the
      development of 90Y radiopharmaceuticals.

PMID- 23009586
TI  - Nanomaterials in the field of design ergonomics: present status.
AB  - Application of nanotechnology and nanomaterials is not new in the field of
      design, but a recent trend of extensive use of nanomaterials in product and/or
      workplace design is drawing attention of design researchers all over the world.
      In the present paper, an attempt has been made to describe the diverse use of
      nanomaterials in product and workplace design with special emphasis on ergonomics
      (occupational health and safety; thermo-regulation and work efficiency, cognitive
      interface design; maintenance of workplace, etc.) to popularise the new
      discipline 'nanoergonomics' among designers, design users and design researchers.
      Nanoergonomics for sustainable product and workplace design by minimising
      occupational health risks has been felt by the authors to be an emerging research
      area in coming years. PRACTITIONER SUMMARY: Use of nanomaterials in the field of
      design ergonomics is less explored till date. In the present review, an attempt
      has been made to extend general awareness among ergonomists/designers about
      applications of nanomaterials/nanotechnology in the field of design ergonomics
      and about health implications of nanomaterials during their use.

PMID- 23009587
TI  - Abstracts of the XXX Annual Scientific Meeting of the British Blood Transfusion
      Society. September 27-28, 2012. Harrogate, United Kingdom.

PMID- 23009588
TI  - The 'bra sign' in breast cancer.

PMID- 23009589
TI  - A multi-pad electrode based functional electrical stimulation system for
      restoration of grasp.
AB  - BACKGROUND: Functional electrical stimulation (FES) applied via transcutaneous
      electrodes is a common rehabilitation technique for assisting grasp in patients
      with central nervous system lesions. To improve the stimulation effectiveness of
      conventional FES, we introduce multi-pad electrodes and a new stimulation
      paradigm. METHODS: The new FES system comprises an electrode composed of small
      pads that can be activated individually. This electrode allows the targeting of
      motoneurons that activate synergistic muscles and produce a functional movement.
      The new stimulation paradigm allows asynchronous activation of motoneurons and
      provides controlled spatial distribution of the electrical charge that is
      delivered to the motoneurons. We developed an automated technique for the
      determination of the preferred electrode based on a cost function that considers
      the required movement of the fingers and the stabilization of the wrist joint.
      The data used within the cost function come from a sensorized garment that is
      easy to implement and does not require calibration. The design of the system also
      includes the possibility for fine-tuning and adaptation with a manually
      controllable interface. RESULTS: The device was tested on three stroke patients.
      The results show that the multi-pad electrodes provide the desired level of
      selectivity and can be used for generating a functional grasp. The results also
      show that the procedure, when performed on a specific user, results in the
      preferred electrode configuration characteristics for that patient. The findings
      from this study are of importance for the application of transcutaneous
      stimulation in the clinical and home environments.

PMID- 23009590
TI  - Induction of beta-glucuronidase release by cytostatic agents in small tumors.
AB  - Extracellular beta-glucuronidase (beta-GUS) in tumors has been investigated as a
      target enzyme for prodrug therapy. However, despite encouraging preclinical
      results, animal studies also indicate that the success of prodrug therapy might
      be limited by the insufficient prodrug-converting enzyme activity, especially in
      small tumors. We hypothesized that a single dose of a cytostatic drug might
      induce the release of beta-GUS in small tumors, resulting in increased levels of
      extracellular beta-GUS and consequently a higher efficacy of the prodrug
      treatment. Here we examine the extent of beta-GUS release in small C6 glioma
      tumors after a single treatment of doxorubicin (DOX), carmustine (BCNU) and tumor
      necrosis factor alpha (TNF-alpha) with positron emission tomography (PET) and the
      tracer 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-beta-d
      glucopyronuronate, [(18)F]FEAnGA, which has been proven to be selective for
      extracellular beta-GUS. Induction of beta-GUS release was first investigated in
      cultured C6 glioma cells. In addition, a [(18)F]FEAnGA PET study was performed in
      C6 tumor-bearing rats 48 h after a single treatment with different cytostatics to
      evaluate the extent of beta-glucuronidase release. The cleavage of [(18)F]FEAnGA
      by beta-GUS was analyzed in tumor homogenates. The induction of tumor necrosis
      and leukocyte infiltration was confirmed by histochemical analysis and flow
      cytometry. The in vitro studies indicated that all treatments resulted in a
      decline of viable cells and an increase of extracellular beta-GUS activity. PET
      studies confirmed that beta-GUS was released in vivo and the distribution volume
      of the PET tracer [(18)F]FEAnGA in C6 gliomas was increased significantly by 15
      70%, depending on the treatment. Histochemical analysis of the tumors indicated
      that carmustine and TNF-alpha treatment caused a larger necrotic area with the
      absence of infiltrating immune cells, whereas doxorubicin induced an increase in
      leukocyte infiltration. These results were confirmed by flow cytometry. In
      conclusion, the present study demonstrates that a single dose of a cytostatic
      agent is able to increase the release of beta-GUS. The release in beta-GUS can be
      monitored by [(18)F]FEAnGA PET in a noninvasive manner. This study may open the
      way to a two-step chemotherapy-prodrug approach, in which tumors are treated with
      a single dose of a cytostatic drug prior to prodrug treatment.

PMID- 23009591
TI  - In search of the cancer candidate: can lay epidemiology help?
AB  - First published in 1991, the ideas embedded in 'Lay epidemiology and the
      prevention paradox' offered a novel and rational explanation for the lay public's
      failure to fully engage with the lifestyle messages offered by health educators.
      During the course of a large ethnographic study in South Wales, Davison and
      colleagues described the emergence of what they termed the coronary candidate.
      Candidacy provides a 'cultural mechanism' that facilitates the estimation of risk
      for coronary heart disease. The model has rarely been applied to other major
      illnesses. This article presents findings from a study that sought to explore the
      lay epidemiology model, candidacy and cancer. In a series of in-depth individual
      interviews, members of the lay public discussed their ideas about cancer, and
      what emerged was an explanatory hierarchy to account for cancer events. Yet the
      random and unpredictable nature of cancer was emphasised as well as a general
      reluctance to accept the idea of cancer candidacy.

PMID- 23009592
TI  - Associations of insulin-like growth factor-I and its binding proteins and
      testosterone with frailty in older men.
AB  - OBJECTIVE: Ageing is associated with frailty and decreased anabolic hormones,
      insulin-like growth factor-I (IGF-I) and testosterone. We hypothesized that
      components of the IGF-I system, in conjunction with testosterone, modulate
      frailty risk in the elderly. We examined associations between IGF-I, its binding
      proteins IGFBP1 and IGFBP3 and testosterone with frailty in men. DESIGN:
      Observational study of 3 447 community-dwelling men aged 70-89 years assessed in
      2001-04, with 1 654 reassessed in 2008-09. METHODS: Baseline total IGF-I, IGFBP1,
      IGFBP3 and testosterone were assayed. Frailty was assessed using the FRAIL scale,
      comprising 5 domains: fatigue; difficulty climbing stairs; difficulty walking
      >100 m; >5 illnesses; weight loss >5%. Men with >= 3 domains were considered
      frail. RESULTS: At baseline, 527 men (15.3%) were frail. Frail men had lower
      IGFBP3 (3 630 ng/ml vs not frail: 3 800 ng/ml, P < 0.001) and comparable IGFBP1
      (23.5 vs 21.5 ng/ml, P = 0.09). In multivariate analyses, higher IGFBP1 was
      associated with increased prevalence of frailty (highest vs lowest quartile
      Q4:Q1, adjusted odds ratio [OR] = 1.39, 95% CI = 1.03-1.88). New-onset frailty
      arose in 260 (17.5%) of 1 484 men. Lower baseline IGF-I predicted new-onset
      frailty (Q1:Q4 OR = 1.48, 95% CI = 1.00-2.20) as did higher IGFBP1 (Q4:Q1 OR =
      1.59, 95% CI = 1.01-2.50). Men with both IGF-I and free testosterone in Q1 had
      greater odds of prevalent frailty (OR = 2.13, 95% CI = 1.54-2.95). CONCLUSIONS:
      Older men with higher IGFBP1 level, or both lower IGF-I and testosterone, are
      more likely to be frail, while those with lower IGF-I and higher IGFBP1 are more
      likely to become frail. Components of the IGF-I system may be biomarkers or
      independent predictors of frailty.

PMID- 23009593
TI  - ESTclean: a cleaning tool for next-gen transcriptome shotgun sequencing.
AB  - BACKGROUND: With the advent of next-generation sequencing (NGS) technologies,
      full cDNA shotgun sequencing has become a major approach in the study of
      transcriptomes, and several different protocols in 454 sequencing have been
      invented. As each protocol uses its own short DNA tags or adapters attached to
      the ends of cDNA fragments for labeling or sequencing, different contaminants may
      lead to mis-assembly and inaccurate sequence products. RESULTS: We have designed
      and implemented a new program for raw sequence cleaning in a graphical user
      interface and a batch script. The cleaning process consists of several modules
      including barcode trimming, sequencing adapter trimming, amplification primer
      trimming, poly-A tail trimming, vector screening and low quality region trimming.
      These modules can be combined based on various sequencing applications.
      CONCLUSIONS: ESTclean is a software package not only for cleaning cDNA sequences,
      but also for helping to develop sequencing protocols by providing summary tables
      and figures for sequencing quality control in a graphical user interface. It
      outperforms in cleaning read sequences from complicated sequencing protocols
      which use barcodes and multiple amplification primers.

PMID- 23009594
TI  - Police referrals to a psychiatric hospital: experiences of nurses caring for
      police-referred admissions.
AB  - Police are a major source of referral to psychiatric hospitals in industrialized
      countries with mental health legislation. However, little attention has been paid
      to nurses' experience of caring for police-referred patients to psychiatric
      hospitals. This study utilized a Heideggerian phenomenological framework to
      explore the experiences of nine nurses caring for patients referred by the
      police, through semistructured interviews. Two major themes emerged from the
      hermeneutic analyses of interviews conducted with nurse participants: (i)
      'expecting "the worst" '; and (ii) 'balancing therapeutic care and forced
      treatment'. Expecting 'the worst' related to the perceptions nurse participants
      had about patients referred by the police. This included two sub-themes: (i) 'we
      are here to care for whoever they bring in'; and (ii) 'but who deserves care?'
      The second theme balancing therapeutic care and forced treatment included the sub
      themes: (i) 'taking control, taking care'; and (ii) 'managing power'. The study
      raises ethical and skill challenges for nursing including struggling with the
      notion of who deserves care, and balancing the imperatives of legislation with
      the need to work within a therapeutic framework.

PMID- 23009595
TI  - Na(+)/K(+)-ATPase expression changes in the rabbit lacrimal glands during
      pregnancy.
AB  - PURPOSE: To investigate the expressional changes of Na(+)/K(+)-ATPase subunits in
      the lacrimal glands (LG) of term pregnant rabbits. METHODS: LG were obtained from
      term pregnant rabbits and age-matched female control rabbits for laser capture
      microdissection (LCM), real time RT-PCR, western blot, and immunofluorescence.
      The mRNA and proteins of alpha1, alpha2, beta1, beta2, and beta3 subunits of
      Na(+)/K(+)-ATPase were detected and quantified. RESULTS: Although only the mRNA
      for beta3 from whole LG of pregnant rabbits was significantly different from that
      of normal controls, many mRNA levels for alpha1, alpha2, beta1, beta2, and beta3
      from acini and epithelial cells from various duct segments that were collected by
      LCM were significantly different from those of normal control rabbits. Western
      blots demonstrated that the expressions of all three beta subunits were
      significantly higher in pregnant rabbits, while both alpha subunits remained
      unchanged during pregnancy. Interestingly, immunofluorescence results showed that
      the distribution patterns of all Na(+)/K(+)-ATPase subunits during pregnancy were
      similar to those of the control rabbits. CONCLUSIONS: Changes were found in mRNA
      and protein expressions of Na(+)/K(+)-ATPase subunits in LG from term pregnant
      rabbits and these changes suggest a role in the pregnancy-related LG secretion
      changes and dry eye symptoms observed in these animals.

PMID- 23009596
TI  - Preventing protein adsorption and macrophage uptake of gold nanoparticles via a
      hydrophobic shield.
AB  - Polyethylene glycol (PEG) surface coatings are widely used to render stealth
      properties to nanoparticles in biological applications. There is abundant
      literature on the benefits of PEG coatings and their ability to reduce protein
      adsorption, to diminish nonspecific interactions with cells, and to improve
      pharmacokinetics, but very little discussion of the limitations of PEG coatings.
      Here, we show that physiological concentrations of cysteine and cystine can
      displace methoxy-PEG-thiol molecules from the gold nanoparticle (GNP) surface
      that leads to protein adsorption and cell uptake in macrophages within 24 h.
      Furthermore, we address this problem by incorporating an alkyl linker between the
      PEG and the thiol moieties that provides a hydrophobic shield layer between the
      gold surface and the hydrophilic outer PEG layer. The mPEG-alkyl-thiol coating
      greatly reduces protein adsorption on GNPs and their macrophage uptake. This has
      important implications for the design of GNP for biological systems.

PMID- 23009597
TI  - Simple and real-time colorimetric assay for glycosidases activity using
      functionalized gold nanoparticles and its application for inhibitor screening.
AB  - The development of real-time assays for enzymes has been receiving a great deal
      of attention in biomedical research recently. Self-immolative elimination is the
      spontaneous and irreversible disassembly of a multicomponent construct into its
      constituent fragments through a cascade of elimination processes, in response to
      external stimuli. Here, we report a simple and real-time colorimetric assay for
      glycosidases (beta-galactosidase and beta-glucosidase). Self-immolative
      elimination was utilized to release amines to give rise to aggregation and color
      change by electrostatic attraction after cleavage of the trigger by enzymes
      displayed on functionalized gold nanoparticles (Gal-Lip-AuNPs and Glc-Lip-AuNPs,
      where AuNPs denotes gold nanoparticles). The detection limits for beta
      galactosidase and beta-glucosidase were as low as 9.2 and 22.3 nM at 20 min, and
      they improved slightly over time. Thus, glycosidase activity was detected
      successfully in real time, and this technique could be used for glycosidase
      inhibitor screening, based on real-time colorimetric variation.

PMID- 23009598
TI  - Diagnostic issues and capabilities in 48 isolation facilities in 16 European
      countries: data from EuroNHID surveys.
AB  - BACKGROUND: Highly infectious diseases (HIDs) are defined as being transmissible
      from person to person, causing life-threatening illnesses and presenting a
      serious public health hazard. The sampling, handling and transport of specimens
      from patients with HIDs present specific bio-safety concerns. FINDINGS: The
      European Network for HID project aimed to record, in a cross-sectional study, the
      infection control capabilities of referral centers for HIDs across Europe and
      assesses the level of achievement to previously published guidelines. In this
      paper, we report the current diagnostic capabilities and bio-safety measures
      applied to diagnostic procedures in these referral centers. Overall, 48 isolation
      facilities in 16 European countries were evaluated. Although 81% of these
      referral centers are located near a biosafety level 3 laboratory, 11% and 31% of
      them still performed their microbiological and routine diagnostic analyses,
      respectively, without bio-safety measures. CONCLUSIONS: The discrepancies among
      the referral centers surveyed between the level of practices and the European
      Network of Infectious Diseases (EUNID) recommendations have multiple reasons of
      which the interest of the individuals in charge and the investment they put in
      preparedness to emerging outbreaks. Despite the fact that the less prepared
      centers can improve by just updating their practice and policies any support to
      help them to achieve an acceptable level of biosecurity is welcome.

PMID- 23009599
TI  - Mindfulness-based stress reduction for low back pain. A systematic review.
AB  - BACKGROUND: Mindfulness-based stress reduction (MBSR) is frequently used for pain
      conditions. While systematic reviews on MBSR for chronic pain have been
      conducted, there are no reviews for specific pain conditions. Therefore a
      systematic review of the effectiveness of MBSR in low back pain was performed.
      METHODS: MEDLINE, the Cochrane Library, EMBASE, CAMBASE, and PsycInfo were
      screened through November 2011. The search strategy combined keywords for MBSR
      with keywords for low back pain. Randomized controlled trials (RCTs) comparing
      MBSR to control conditions in patients with low back pain were included. Two
      authors independently assessed risk of bias using the Cochrane risk of bias tool.
      Clinical importance of group differences was assessed for the main outcome
      measures pain intensity and back-specific disability. RESULTS: Three RCTs with a
      total of 117 chronic low back pain patients were included. One RCT on failed back
      surgery syndrome reported significant and clinically important short-term
      improvements in pain intensity and disability for MBSR compared to no treatment.
      Two RCTs on older adults (age >= 65 years) with chronic specific or non-specific
      low back pain reported no short-term or long-term improvements in pain or
      disability for MBSR compared to no treatment or health education. Two RCTs
      reported larger short-term improvements of pain acceptance for MBSR compared to
      no treatment. CONCLUSION: This review found inconclusive evidence of
      effectiveness of MBSR in improving pain intensity or disability in chronic low
      back pain patients. However, there is limited evidence that MBSR can improve pain
      acceptance. Further RCTs with larger sample sizes, adequate control
      interventions, and longer follow-ups are needed before firm conclusions can be
      drawn.

PMID- 23009600
TI  - Intravenous immunoglobulin treatment in a patient with adrenomyeloneuropathy.
AB  - BACKGROUND: Adrenomyeloneuropathy (AMN) is one of several phenotypes of the
      adrenoleukodystrophy spectrum caused by mutations in the ABCD1 gene on the X
      chromosome. An inflammatory component is part of the disease complex ranging from
      severe childhood CNS demyelination to spinal cord and peripheral nerve
      degeneration. CASE PRESENTATION: We present a patient with clinical progressive
      AMN and severe lower limb pain. Longitudinal brain magnetic resonance
      spectroscopy showed a constant slightly elevated myoinositol/total creatine ratio
      during the five year treatment period, probably reflecting demyelination,
      microglial activation and gliosis, indicating an inflammatory response. The pain
      was refractory to conventional therapy but intravenous immunoglobulin (IVIG)
      treatment was highly efficient. CONCLUSION: IVIG may be considered as a last
      resort for treatment of refractory pain in AMN patients with indications of an
      inflammatory component.

PMID- 23009602
TI  - Development of an improved method for trace analysis of quinolones in eggs of
      laying hens and wildlife species using molecularly imprinted polymers.
AB  - A sensitive, selective, and efficient method was developed for simultaneous
      determination of 11 fluoroquinolones (FQs), ciprofloxacin, danofloxacin,
      difloxacin, enrofloxacin, flumequine, marbofloxacin, norfloxacin, ofloxacin,
      oxolinic acid, pipemidic acid, and sarafloxacin, in eggs by molecularly imprinted
      polymer (MIP) and column liquid chromatography-electrospray ionization-tandem
      mass spectrometry (LC-ESI-MS/MS). Samples were diluted with 50 mM sodium
      dihydrogen phosphate at pH 7.4, followed by purification with a commercial MIP
      (SupelMIP SPE-Fluoroquinolones). Recoveries for the 11 quinolones were in the
      range of 90-106% with intra- and interday relative standard deviation ranging
      from 1 to 6% and from 3 to 8%, respectively. Limits of detection (LODs) were 0.12
      0.85 ng/g, and limits of quantification (LOQs) were 0.36 and 2.59 ng/g, whereas
      the decision limit (CC(alpha)) and detection capability (CC(beta)) ranged from
      0.46 to 3.35 ng/g and from 0.59 to 4.12 ng/g, respectively. The calculated
      relevant validation parameters are in an acceptable range and in compliance with
      the requirements of Commission Decision 2002/657/EC. Moreover, a comparison to
      two other sample treatments [solid-phase extraction (SPE) and solvent extraction]
      has been carried out. The method was applied to lying hens, Japanese quail, and
      black-headed gull eggs, in which FQs were not found. The method was also applied
      to study the depletion of sarafloxacin in eggs.

PMID- 23009601
TI  - Markers for severity of illness associated with decreased snoring in toddlers
      born ELGA.
AB  - AIM: To describe the prevalence of paediatric sleep disordered breathing (SDB)
      symptoms in extremely low gestational age infants and identify neonatal risk
      factors, including early exposure to hypoxia and hyperoxia. METHODS: Patients <28
      weeks gestation were monitored with high-resolution pulse oximetry.
      Hypoxia/hyperoxia variables were defined as percentage time of first 4 weeks of
      life that SaO(2) < 80% or SaO(2) > 98%, respectively. Parents completed part of
      the OSA-18 questionnaire for symptoms of SDB at 18-22 months. Logistic regression
      was used to test the association between risk factors and sleep symptoms.
      RESULTS: Of 182 patients recruited, 138 (76%) completed the questionnaire. The
      mean gestation was 26 weeks, and mean birth weight 887 grams. Loud snoring (21%)
      and restless sleep (24%) were the most prevalent symptoms. Female sex was
      associated with an increased risk of loud snoring (OR, 2.7; CI, 1.13-6.5).
      Prolonged mechanical ventilation, necrotizing enterocolitis and prolonged
      caffeine use, however, were inversely correlated with loud snoring. Neither
      neonatal hypoxia nor hyperoxia were associated with sleep symptoms. CONCLUSIONS:
      While the prevalence of sleep disordered breathing symptoms is similar to
      reported rates, we found a sex difference not previously reported. Interestingly,
      markers for severity of illness show a pattern of being protective against loud
      snoring.

PMID- 23009603
TI  - The chiral herbicide beflubutamid (II): Enantioselective degradation and
      enantiomerization in soil, and formation/degradation of chiral metabolites.
AB  - Beflubutamid is a chiral soil herbicide currently marketed as racemate against
      dicotyledonous weeds in cereals. Biotests have shown that (-)-beflubutamid is at
      least 1000* more active than (+)-beflubutamid. Potential substitution of the
      racemate by (-)-beflubutamid should therefore be further considered. Here, we
      investigated the degradation behavior in soils and formation and degradation of
      two chiral metabolites. Laboratory incubation experiments were performed with an
      alkaline and an acidic soil. The compounds were analyzed by enantioselective GC
      MS. Degradation rate constants were determined by kinetic modeling. In the
      alkaline soil, degradation of beflubutamid was slightly enantioselective, with
      slower degradation of the herbicidally active (-)-enantiomer. In the acidic soil,
      however, both enantiomers were degraded at similar rates. In contrast,
      degradation of a phenoxybutanamide metabolite was highly enantioselective. Chiral
      stability of beflubutamid and its metabolites was studied in separate incubations
      with the pure enantiomers in the same soils. In these experiments, (-)
      beflubutamid was not converted to the nonactive (+)-enantiomer and vice versa.
      Significant enantiomerization was, however, observed for the major metabolite, a
      phenoxybutanoic acid. With regard to biological activity and behavior in soils,
      enantiopure (-)-beflubutamid definitively has the potential to substitute for the
      racemic herbicide. 

PMID- 23009604
TI  - Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel
      protein tyrosine phosphatase 1B inhibitors.
AB  - A series of 5,7-dihydroxyflavanone derivatives were synthesized and identified as
      reversible and competitive protein tyrosine phosphatase (PTP) 1B inhibitors with
      IC50 values in the micromolar range. Compound 4k had the most potent in vitro
      inhibition activity against PTP1B (IC50 = 2.37 +/- 0.37 MUM) and the greatest
      selectivity (3.7-fold) for PTP1B relative to T-cell protein tyrosine phosphatase.
      Cell-based studies revealed that 4k was membrane-permeable and enhanced insulin
      receptor tyrosine phosphorylation in CHO/hIR cells.

PMID- 23009605
TI  - Forensic expertise and judicial practice: evidence or proof?
AB  - RATIONALE, AIMS AND OBJECTIVES: This study presents for discussion the
      possibility of adopting a hypothesis of absolute truth in forensic serology and
      DNA testing of biological traces, taking into account identification probability,
      which is usually assumed to be greater than 95%. Can this be so? Established
      identity and mathematically calculated probability below this rate is not false
      because it depends on the sensitivity of the method, the possible number of
      variations and theoretical combinations. The result from a study can be
      considered a 100% identification result only if this study takes account of
      absolutely all quantitative criteria that characterize it. METHODS: Under the
      conditions of continually evolving theory and practice, and the introduction of
      modified and expanded methods for analysis of biological materials, it may
      therefore be asked which method considers 'everything'. Although this finding is
      nihilistic, it reflects a truth, which we can define as absolute. In forensic
      practice, research methods assumed to be orientation ones and others identified
      as evidence for the presence of biological traces on objects carriers, are
      routinely employed. RESULTS: Based on several groups of forensic cases, the
      question of the limits of precision and relevance of the results to the
      categories of evidence and proof is formulated and discussed. Three groups of
      expertise cases are presented, which warrant discussion: (i) a study of condoms
      with genetic material on both sides: female DNA on the outer surface and male DNA
      on the inner. What is this evidence for or what does it prove?; (ii) a study of
      cigarette butts found at a crime scene with deposited cellular material from the
      offender. Is this evidence or proof?; (iii) the DNA expertise in the case of
      controversial parental origin or the vasectomy of the man referred to as the
      father. CONCLUSIONS: What will the court choose as proof or is it a case of
      mutually exclusive evidence? Such considerations lead to the dilemma: 'evidence
      or proof'?

PMID- 23009607
TI  - Washing when the sun is shining! How users interact with a household energy
      management system.
AB  - To make optimal use of sustainable energy, domestic electricity consumption
      should shift to match local supply conditions. Energy management systems (EMS)
      are a new sustainable technology that can help to disrupt consumers' habits
      concerning electricity consumption, whilst reinforcing desired behaviours. This
      research examined the factors that influence the likelihood that people will
      shift their electricity consumption to match sustainable supply. Twenty-one
      interviews were conducted with households who had used the EMS 'Smart Wash' for
      several months. The findings showed that the likelihood of behaviour change is
      influenced by a combination of the user's motivation, specific contextual factors
      and the design of the EMS. Based on these results, several recommendations are
      given for the future design of EMSs. PRACTITIONER SUMMARY: Energy management
      systems (EMS) are a new technology that encourages people to shift electricity
      consumption to match local solar supply. Interviews among users of an EMS showed
      that the likelihood of behaviour change is influenced by the combination of the
      user's motivation, contextual factors and the EMS design.

PMID- 23009606
TI  - Periodontal disease: the influence of metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that
      include obesity, impaired glucose tolerance or diabetes, hyperinsulinemia,
      hypertension, and dyslipidemia. Recently, more attention has been reserved to the
      correlation between periodontitis and systemic health. MetS is characterized by
      oxidative stress, a condition in which the equilibrium between the production and
      the inactivation of reactive oxygen species (ROS) becomes disrupted. ROS have an
      essential role in a variety of physiological systems, but under a condition of
      oxidative stress, they contribute to cellular dysfunction and damage. Oxidative
      stress may act as a common link to explain the relationship between each
      component of MetS and periodontitis. All those conditions show increased serum
      levels of products derived from oxidative damage, promoting a proinflammatory
      state. Moreover, adipocytokines, produced by the fat cells of fat tissue, might
      modulate the balance between oxidant and antioxidant activities. An increased
      caloric intake involves a higher metabolic activity, which results in an
      increased production of ROS, inducing insulin resistance. At the same time, obese
      patients require more insulin to maintain blood glucose homeostasis - a state
      known as hyperinsulinemia, a condition that can evolve into type 2 diabetes.
      Oxidation products can increase neutrophil adhesion and chemotaxis, thus favoring
      oxidative damage. Hyperglycemia and an oxidizing state promote the genesis of
      advanced glycation end-products, which could also be implicated in the
      degeneration and damage of periodontal tissue. Thus, MetS, the whole of
      interconnected factors, presents systemic and local manifestations, such as
      cardiovascular disease and periodontitis, related by a common factor known as
      oxidative stress.

PMID- 23009608
TI  - Characterization of aroma compounds in Chinese bayberry (Myrica rubra Sieb. et
      Zucc.) by gas chromatography mass spectrometry (GC-MS) and olfactometry (GC-O).
AB  - The aroma-active compounds in Chinese bayberry were identified using gas
      chromatography-olfactometry (GC-O) and GC-mass spectrometry techniques. The
      volatile compounds were extracted using Liquid-liquid extraction, solvent
      assisted flavor evaporation and headspace solid-phase microextraction (HS-SPME),
      respectively. On the basis of odor intensity, the most important aroma compounds
      in Chinese bayberry samples were caryophyllene, menthol, 4-terpineol, linalool
      oxide, linalool, benzyl alcohol, alpha-methylbenzyl alcohol, beta-phenylethanol,
      3-methylbutanoic acid and acetic acid, and so on. Moreover, HS-SPME technique was
      employed to investigate the aroma compounds among immature and mature waxberry
      fruits. The results showed that terpenes (for example, beta-caryophyllene) was
      predominant and its concentration represented over 89.9% of the overall
      compounds, and alcohols, aldehydes, ketones, esters, acids, and others were
      typically present in lesser amounts. Finally, principal component analysis
      revealed that there was also significant difference between immature and mature
      waxberry fruits.

PMID- 23009610
TI  - Relating hydrogen-bonding interactions with the phase behavior of naproxen/PVP K
      25 solid dispersions: evaluation of solution-cast and quench-cooled films.
AB  - In this work, we investigated the relationship between various intermolecular
      hydrogen-bonding (H-bonding) interactions and the miscibility of the model
      hydrophobic drug naproxen with the hydrophilic polymer polyvinylpyrrolidone (PVP)
      across an entire composition range of solid dispersions prepared by quasi
      equilibrium film casting and nonequilibrium melt quench cooling. The binary phase
      behavior in solid dispersions exhibited substantial processing method dependence.
      The solid state solubility of crystalline naproxen in PVP to form amorphous solid
      dispersions was 35% and 70% w/w naproxen in solution-cast films and quench-cooled
      films, respectively. However, the presence of a single mixed phase glass
      transition indicated the amorphous miscibility to be 20% w/w naproxen for the
      films, beyond which amorphous-amorphous and/or crystalline phase separations were
      apparent. This was further supported by the solution state interactions data such
      as PVP globular size distribution and solution infrared spectral profiles. The
      borderline melt composition showed cooling rate dependence of amorphization. The
      glass transition and melting point depression profiles of the system were treated
      with the analytical expressions based on Flory-Huggins mixing theory to
      interpolate the equilibrium solid solubility. FTIR analysis and subsequent
      spectral deconvolution revealed composition and miscibility dependent variations
      in the strength of drug-polymer intermolecular H-bonding. Two types of H-bonded
      populations were evidenced from 25% w/w and 35% w/w naproxen in solution-cast
      films and quench-cooled films, respectively, with the higher fraction of strongly
      H-bonded population in the drug rich domains of phase separated amorphous film
      compositions and highly drug loaded amorphous quench-cooled dispersions.

PMID- 23009609
TI  - A woman with breast cancer and severe impaired lactose tolerance: an intriguing
      therapeutic dilemma.

PMID- 23009611
TI  - Chromosomal structural analysis in carcinoma of the gallbladder.
AB  - BACKGROUND: The etiopathogenesis of gallbladder cancer is still unknown. Both
      environmental and patient factors have been incriminated in its cause. That it is
      found in pockets of epidemiological distribution raises an issue of genetic
      changes associated with it. The aim of this study was to find out the chromosomal
      changes in gallbladder cancer. METHODS: Lymphocyte cell culture was carried out
      on blood of gallbladder cancer patients to determine chromosomal banding
      abnormalities. Native PAGE was also evaluated to analyze lactate dehydrogenase
      (LDH), superoxide dismutase (SOD) and catalase enzyme activity from the same
      blood of gallbladder cancer patients. RESULTS: Out of 30 gallbladder cancer
      patients, 4 male showed breakage on the long arm of chromosome 1 while only one
      male patient showed the translocation from the long arm of chromosome 4 to the
      long arm of chromosome 6 in a male patient. CONCLUSION: The aberrations found in
      our study may suggest underlying genetic predisposition for the development of
      gallbladder cancer. They can act as a marker for gallbladder cancer, which needs
      further study.

PMID- 23009613
TI  - Food work and feeding assistance on hospital wards.
AB  - Approximately 60 per cent of UK patients aged 65 years or older are at risk of
      malnutrition or their situation worsening while in hospital. We report the
      results of a qualitative study embedded in research to prevent malnutrition in
      older people in hospital (the mappmal study). Our aim was to understand and
      describe processes that promote or inhibit nutrition in hospital. Throughout 2009
      we examined meal services at four UK hospital sites across two regional
      locations, focusing on older patients admitted with dementia, for stroke or for
      fractured neck of femur. Data were collected through semi-structured interviews
      with National Health Service staff (n = 54), stakeholders (n = 6), and a focus
      group with former patients and carers (n = 5). We identified ward-based food work
      as a technical and interpersonal challenge in narratives around malnutrition.
      Food work constituted two overlapping spheres of activity: interpersonal
      engagement through feeding assistance and reassurance and the arrangement of
      resources that facilitate meals such as the preparation of food trolleys. Our
      analysis is framed by the literature on emotional labour, dirty work and the
      professionalisation of nursing. We demonstrate how food work is overlooked by
      being conceptualised as common sense and as one of the most mundane and
      elementary tasks in hospitals.

PMID- 23009612
TI  - Smelt was the likely beneficiary of an antifreeze gene laterally transferred
      between fishes.
AB  - BACKGROUND: Type II antifreeze protein (AFP) from the rainbow smelt, Osmerus
      mordax, is a calcium-dependent C-type lectin homolog, similar to the AFPs from
      herring and sea raven. While C-type lectins are ubiquitous, type II AFPs are only
      found in a few species in three widely separated branches of teleost fishes.
      Furthermore, several other non-homologous AFPs are found in intervening species.
      We have previously postulated that this sporadic distribution has resulted from
      lateral gene transfer. The alternative hypothesis, that the AFP evolved from a
      lectin present in a shared ancestor and that this gene was lost in most species,
      is not favored because both the exon and intron sequences are highly conserved.
      RESULTS: Here we have sequenced and annotated a 160 kb smelt BAC clone containing
      a centrally-located AFP gene along with 14 other genes. Quantitative PCR
      indicates that there is but a single copy of this gene within the smelt genome,
      which is atypical for fish AFP genes. The corresponding syntenic region has been
      identified and searched in a number of other species and found to be devoid of
      lectin or AFP sequences. Unlike the introns of the AFP gene, the intronic
      sequences of the flanking genes are not conserved between species. As well, the
      rate and pattern of mutation in the AFP gene are radically different from those
      seen in other smelt and herring genes. CONCLUSIONS: These results provide stand
      alone support for an example of lateral gene transfer between vertebrate species.
      They should further inform the debate about genetically modified organisms by
      showing that gene transfer between 'higher' eukaryotes can occur naturally.
      Analysis of the syntenic regions from several fishes strongly suggests that the
      smelt acquired the AFP gene from the herring.

PMID- 23009614
TI  - Exploiting the pi-acceptor properties of carbene-stabilized phosphorus centered
      trications [L3P]3+: applications in Pt(II) catalysis.
AB  - Reaction of tris(dimethylaminocyclopropenium) substituted phosphine 1 with
      K(2)PtCl(4) afforded the bench stable complex 3 which upon treatment with
      Ag[CB(11)H(6)Cl(6)] turned out to be an excellent catalyst for the transformation
      of a variety of ortho-biaryl substituted alkynes into polycyclic homo- and
      heteroarenes of different size, shape, and curvature through a 6-endo-dig
      cyclization. This constitutes the first example ever reported of using a P(1)
      centered trication as ligand in catalysis. The strong pi-acceptor character of 1
      that derives from its three positive charges substantially increases the
      intrinsic pi-acidity of Pt in complex 1.PtCl(2) and dramatically enhances its
      ability to activate pi-systems toward nucleophilic attack. As a consequence, a
      remarkable acceleration of the model transformation is observed when compared
      with other classical pi-acceptor ligands such as P(OPh)(3) or P(C(6)F(5))(3).
      Moreover, the employment of 1 as ligand also expands the scope of this reaction
      to previously inaccessible substitution patterns. Kinetic studies and deuterium
      labeling experiments as well as density functional theory (DFT) calculations were
      performed in order to explain these findings.

PMID- 23009615
TI  - The challenge of delivering endocrine care and successful transition to adult
      services in adolescents with congenital adrenal hyperplasia: experience in a
      single centre over 18 years.
AB  - BACKGROUND: Congenital adrenal hyperplasia (CAH) has implications throughout a
      patient's life. The challenges of organizing transition from paediatric to adult
      care in endocrinology are recognized. OBJECTIVE: To evaluate whether young people
      with CAH have been successfully transitioned from paediatric care to specialist
      adult services and the influence of the introduction of a Young Person Clinic
      (YPC) where the young person is introduced to the adult endocrinologist. DESIGN,
      PATIENTS AND MEASUREMENTS: Patients aged 16+ years with CAH who had attended the
      adrenal clinic at Royal Manchester Children's Hospital between 1992 and 2009 were
      identified. Clinical information, attendance data in paediatric and adult
      services were obtained from patient records and the electronic appointment
      system. RESULTS: A total of 61 patients (27 men) were identified. Thirty-six
      patients were referred to specialist adult services from the paediatric service;
      eighteen of these (50%) were lost to follow-up (two were never offered an
      appointment). Only 53% of the whole group attended their first new and subsequent
      second appointment (i.e. good early attenders). There was no difference in
      engagement with adult services in those who transitioned through the YPC. Good
      early attenders were less likely to get lost to follow-up compared with poor
      early attenders (11-33% lost to follow-up compared with 63-71%). CONCLUSIONS:
      Half of all young people with CAH referred to specialist adult services are no
      longer attending. Introducing the adult endocrinologist prior to transfer had no
      positive effect on engagement with adult services. Attendance at the first two
      appointments in the adult services should be seen as an indicator of 'reasonable'
      engagement.

PMID- 23009616
TI  - Effect of 300 mT static and 50 Hz 0.1 mT extremely low frequency magnetic fields
      on  Tuber borchii  mycelium.
AB  - The present work aimed to investigate whether exposure to static magnetic field
      (SMF) and extremely low frequency magnetic field (ELF-MF) can induce biomolecular
      changes on  Tuber borchii  hyphal growth. Tuber borchii mycelium was exposed for
      1 h for 3 consecutive days to a SMF of 300 mT or an ELF-MF of 0.1 mT 50 Hz. Gene
      expression and biochemical analyses were performed. In mycelia exposed to ELF-MF,
      some genes involved in hyphal growth, investigated using quantitative real-time
      polymerase chain reaction, were upregulated, and the activity of many glycolytic
      enzymes was increased. On the contrary, no differences were observed in gene
      expression after exposure to SMF treatment, and only the activities of glucose 6
      phosphate dehydrogenase and hexokinase increased. The data herein presented
      suggest that the electromagnetic field can act as an environmental factor in
      promoting hyphal growth and can be used for applicative purposes, such as the set
      up of new in vitro cultivation techniques.

PMID- 23009617
TI  - The yeast factory.
AB  - A report on the 13th International Congress on Yeasts(ICY), held at Madison,
      Wisconsin, USA, 26-30 August 2012.

PMID- 23009618
TI  - Mass spectrometry imaging on porous silicon: investigating the distribution of
      bioactives in marine mollusc tissues.
AB  - Desorption/ionization on porous silicon-mass spectrometry (DIOS-MS) is an
      attractive alternative to conventional matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) for the analysis of low
      molecular weight compounds. Porous silicon (pSi) chips are also suitable as
      support for mass spectrometry imaging (MSI). Here, we report an implementation of
      DIOS-MSI using the biosynthetic organs of a marine mollusc for proof of
      principle. The tissue section is stamped onto a fluorocarbon-functionalized pSi
      chip, which extracts and traps small hydrophobic molecules from the tissue under
      retention of their relative spatial distribution. The section is subsequently
      removed and the chip is imaged without any remaining tissue. We apply this novel
      tissue contact printing approach to investigate the distribution of biologically
      active brominated precursors to Tyrian purple in the hypobranchial gland of the
      marine mollusc, Dicathais orbita, using DIOS-MSI. The tissue contact printing is
      also compatible with other types of desorption/ionization surfaces, such as
      nanoassisted laser desorption/ionization (NALDI) targets.

PMID- 23009619
TI  - Temperature and heart rate responses to exercise following mild traumatic brain
      injury.
AB  - We have previously reported that mild fluid percussion injury (FPI) is associated
      with a heightening of the hypothalamic-pituitary-adrenal axis response during the
      first post-injury weeks. This is the same time period when rehabilitative
      exercise has been strongly suggested to be ineffective. Here, we explored whether
      cardiac and temperature autonomic function may also be compromised during this
      early post-injury period. Following an FPI or sham injury, rats were exercised
      with forced (fRW) or voluntary (vRW) running wheels on post-injury days 0-4 and 7
      11. Results indicated that overall activity levels were decreased and circadian
      rhythm was affected after FPI. Autonomic disruptions became evident when exercise
      was introduced, and these disruptions were dependent upon the characteristics of
      exercise. Elevations in heart rate (HR) and core body temperature (CBT) were
      observed as a response to vRW and fRW. FPI animals had more pronounced increases
      in HR as a result of vRW. Likewise, increases in HR were observed with fRW in all
      animals. A strong stress response has recently been associated with fRW exercise.
      FPI rats exposed to fRW were more responsive to experimental manipulations and
      had higher a CBT after the FRW session. The results suggest that subacute
      exercise, particularly if linked to a strong stress response, may be
      counterproductive. Here we show that cardiac and temperature autonomic function
      are compromised during the subacute period following a mild TBI.

PMID- 23009620
TI  - Illustration of extensive extracellular matrix at the epithelial-mesenchymal
      interface within the renal stem/progenitor cell niche.
AB  - BACKGROUND: Stem/progenitor cells are promising candidates to treat diseased
      renal parenchyma. However, implanted stem/progenitor cells are exposed to a
      harmful atmosphere of degenerating parenchyma. To minimize hampering effects
      after an implantation investigations are in progress to administer these cells
      within an artificial polyester interstitum supporting survival. Learning from
      nature the renal stem/progenitor cell niche appears as a valuable model. At this
      site epithelial stem/progenitor cells within the collecting duct ampulla face
      mesenchymal stem/progenitor cells. Both cell types do not have close contact but
      are separated by a wide interstitium. METHODS: To analyze extracellular matrix in
      this particular interstitium, special contrasting for transmission electron
      microscopy was performed. Kidneys of neonatal rabbits were fixed in solutions
      containing glutaraldehyde (GA) or in combination with cupromeronic blue,
      ruthenium red and tannic acid. RESULTS: GA revealed a basal lamina at the ampulla
      and a bright but inconspicuously looking interstitial space. In contrast, GA
      containing cupromeronic blue exhibits numerous proteoglycan braces lining from
      the ampulla towards the interstitial space. GA containing ruthenium red or tannic
      acid demonstrates clouds of extracellular matrix protruding from the basal lamina
      of the ampulla to the surface of mesenchymal stem/progenitor cells. CONCLUSIONS:
      The actual data show that the interstitium between epithelial and mesenchymal
      stem/progenitor cells contains much more and up to date unknown extracellular
      matrix than earlier observed by classical GA fixation.

PMID- 23009621
TI  - Quantifying the shelter rabbit population: an analysis of Massachusetts and Rhode
      Island animal shelters.
AB  - Scholarly work on the nonhuman animal shelter population has widely focused on
      cats and dogs. As a result, little is known about the population dynamics of
      domestic rabbits (Oryctolagus cuniculus) in shelters. The records from 4
      companion animal shelters in Massachusetts and Rhode Island were analyzed to
      describe these dynamics. A majority of the rabbits at the 4 shelters were
      surrendered by their caregivers, were between 1 and 6 years old, and were
      unaltered at the time of intake. The most common reasons for surrender were the
      caregivers' inability to care for the rabbits or a lack of interest in doing so.
      Over half of the total rabbit population was subsequently adopted and the overall
      live release rate (percentage of rabbits leaving the shelter alive) was 75.54%.
      In some cases, the use of a foster care system was correlated with a decrease in
      the euthanasia rate. The results from this study will help the sheltering field
      clarify the scope of the problem of homeless rabbits.

PMID- 23009622
TI  - Lion, ungulate, and visitor reactions to playbacks of lion roars at Zoo Atlanta.
AB  - Felids in captivity are often inactive and elusive in zoos, leading to a
      frustrating visitor experience. Eight roars were recorded from an adult male lion
      and played back over speakers as auditory enrichment to benefit the lions while
      simultaneously enhancing the zoo visitor experience. In addition, ungulates in an
      adjacent exhibit were observed to ensure that the novel location and increased
      frequency of roars did not lead to a stress or fear response. The male lion in
      this study roared more in the playback phase than in the baseline phases while
      not increasing any behaviors that would indicate compromised welfare. In
      addition, zoo visitors remained at the lion exhibit longer during playback. The
      nearby ungulates never exhibited any reactions stronger than orienting to
      playbacks, identical to their reactions to live roars. Therefore, naturalistic
      playbacks of lion roars are a potential form of auditory enrichment that leads to
      more instances of live lion roars and enhances the visitor experience without
      increasing the stress levels of nearby ungulates or the lion themselves, who
      might interpret the roar as that of an intruder.

PMID- 23009623
TI  - Dairy cow behavior and welfare implications of time waiting before entry into the
      milking parlor.
AB  - The objective of this study was to investigate dairy cows' time spent in the
      possibly stressful waiting area (WA) of the milking parlor (MP) and their
      behavioral patterns while there and thereby investigate comparative effects on
      their welfare. The experiments were carried out in 3 loose-housing cowsheds. The
      study consisted of a total of 3,522 observations of individual dairy cows.
      Depending on the group size and the number of places in the MP, cows' waiting
      times in the WA were as high as 1:42:22 (h:mm:ss). In Cowsheds I and II, only one
      third of cows were observed ruminating in the WA, and up to 52% of cows were
      observed ruminating in the WA of Cowshed III where the feeding group size was the
      smallest, waiting time the shortest, and space per cow the largest. Cows spending
      more time in the WA have limited opportunities to behave normally; therefore, the
      welfare of these cows in particular is poor.

PMID- 23009624
TI  - Shelter animal management and trends in Taiwan.
AB  - Trends in the number of dogs entering and departing Taiwan public shelters are
      analyzed in this article. There were 40 public shelters surveyed from 2000 to
      2005 for dog entries and departures. The results indicate that (a) adoption rates
      and relinquished animal numbers increased, and euthanasia rates decreased at the
      beginning of the study, but they are showing signs of reversal; (b) shelters in
      cities have higher adoption rates than those in rural areas; (c) euthanasia
      remains the main means of controlling dog numbers in most shelters; and (d)
      potential adopters in Taiwan prioritize animal health and body size when
      selecting dogs for adoption. There is a need for increased and persistent public
      education to ensure continued progress is made in encouraging people to treat
      companion animals responsibly. In addition to educational efforts, creating new,
      specialized shelters for housing highly adoptable animals can alleviate the space
      constraint problems in existing kennels and improve the welfare of stray dogs.

PMID- 23009625
TI  - Effects of single-use and group-use enrichment on stereotypy and intragroup
      aggressive and affiliative behaviors of a social group of squirrel monkeys
      (Saimiri sciureus) at the Singapore Zoo.
AB  - Four food-based enrichment devices were used to test the effects of single-use
      and group-use enrichment devices on stereotypy, intragroup aggression, and
      affiliation in a compatible group of 5 squirrel monkeys (Saimiri sciureus). All
      enrichment devices were found to reduce overall stereotypic behavior from
      baseline levels (without enrichment). The occurrence of stereotypic behavior
      differed between individual squirrel monkeys with an adult female showing the
      highest level of stereotypic behavior. This individual also showed the highest
      usage of enrichment devices, and stereotypic behavior was significantly reduced
      when enrichment was applied. The occurrence of stereotypic behavior did not
      differ significantly between single-use and group-use enrichment treatments.
      Higher intragroup aggression and lower affiliation were observed during the
      provision of enrichment compared with baseline levels. However, aggressive
      behavior was higher and affiliation lower during single-use enrichment compared
      with group-use enrichment. The results of this study showed that enrichment had
      positive effects on alleviating stereotypic behavior in a group of zoo-housed
      squirrel monkeys and such effects were similar when group-use and single-use
      enrichment devices were used, but with variations between individuals. The
      application of enrichment, particularly single-use enrichment devices, elicited
      higher levels of aggression within the group and lower affiliation. Such effects
      could curtail the benefits of original enrichment goals as higher intragroup
      aggression could lead to higher stress levels within the group. When food-based
      enrichment for social nonhuman primates is implemented, the most appropriate
      methods to alleviate undesirable behavior without additional negative effects
      such as increased group aggression should be considered.

PMID- 23009626
TI  - Physiological responses in wild broodstocks of the Caspian Kutum (Rutilus frisii
      kutum) subjected to transportation stress.
AB  - Caspian Kutum (Rutilus frisii kutum) broodstocks in the wild were subjected to 2
      different densities (100 and 300 kg m(-3)) for 2 hr of transport, and their
      physiological responses were examined. Fifteen fish were placed into the plastic
      container for each replicate and blood was taken at 0, 10, 30, 60, and 120 min
      after transportation in different densities. Mean levels of cortisol and glucose
      as primary and secondary responses to the stress were significantly different
      between densities. Significant differences in both densities were observed in
      cortisol for all times and glucose levels at 30 and 120 min after transportation,
      and the highest values were found in both densities at 120 min. Testosterone
      concentrations declined considerably in the first 10 min, and then they showed a
      gradual decrease with a significant difference between 2 densities at 10 and 30
      min after transportation. Serum estradiol reached the lowest level at 120 min
      after transportation, and differences were significant between the 2 densities
      after 30 min. Based on the results, it was concluded that Kutum broodstocks are
      sensitive to transport, especially at high density. Therefore, welfare during
      transport should be considered.

PMID- 23009627
TI  - Circadian rhythm of salivary cortisol in Asian elephants (Elephas maximus): a
      factor to consider during welfare assessment.
AB  - Elevated glucocorticoid levels during an extended time period might be a stress
      indicator in nonhuman animals. Therefore, knowledge of the circadian pattern of
      cortisol secretion is very important to correctly interpret data obtained for
      welfare assessment of animals in captivity through salivary cortisol. In order to
      define the circadian rhythm of salivary cortisol secretion in the Asian elephant
      (Elephas maximus), morning and evening saliva samples of 3 Asian elephants were
      collected and analyzed by radioimmunoassay. Significantly higher salivary
      cortisol concentrations were found in the morning than in the evening in all
      individuals. These results show that salivary cortisol of Asian elephants follows
      a diurnal pattern of secretion, which could be taken into account when using this
      methodology to assess welfare in captive Asian elephants.

PMID- 23009630
TI  - A new score predicting the survival of patients with spinal cord compression from
      myeloma.
AB  - BACKGROUND: This study was performed to create and validate a scoring system for
      the survival of patients with malignant spinal cord compression (SCC) from
      myeloma. METHODS: Of the entire cohort (N = 216), 108 patients were assigned to a
      test group and 108 patients to a validation group. In the test group, nine pre
      treatment factors including age, gender, Eastern Cooperative Oncology Group
      performance status (ECOG-PS), number of involved vertebrae, ambulatory status
      prior to radiotherapy, other bone lesions, extraosseous lesions, interval from
      first diagnosis of myeloma to radiotherapy of SCC, and the time developing motor
      deficits were retrospectively analyzed. RESULTS: On univariate analysis, improved
      survival was associated with ECOG-PS 1-2 (p = 0.006), being ambulatory (p =
      0.005), and absence of other bone lesions (p = 0.019). On multivariate analysis,
      ECOG-PS (p = 0.036) and ambulatory status (p = 0.037) were significant; other
      bone lesions showed a strong trend (p = 0.06). These factors were included in the
      score. The score for each factor was determined by dividing the 12-month survival
      rate (in%) by 10. The total risk score was the sum of the three factor scores and
      ranged from 19 to 24 points. Three prognostic groups were designed with the
      following 12-month survival rates: 49% for 19-20 points, 74% for 21-23 points,
      and 93% for 24 points (p= 0.002). In the validation group, the 12-month survival
      rates were 51%, 80%, and 90%, respectively (p < 0.001). CONCLUSIONS: This score
      appears reproducible, because the 12-month survival rates of both the test and
      the validation group were very similar. This new survival score can help
      personalize the treatment of patients with SCC from myeloma and can be of benefit
      when counseling patients.

PMID- 23009631
TI  - Epistemological and methodological significance of quantitative studies of
      psychomotor activity for the explanation of clinical depression.
AB  - RATIONALE, AIMS AND OBJECTIVES: Psychomotor disturbances have been regarded as
      cardinal symptoms of depression for centuries and their objective assessment may
      have predictive value with respect to the severity of clinical depression,
      treatment outcome and prognosis of the affective disorder. METHODS: Montgomery
      Asberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Anxiety (HAM
      A). Psychomotor indicators of activity and reactivity were objectively recorded
      and measured by means of computerized ultrasonographic craniocorpography.
      RESULTS: We found a statistically significant correlation between disturbances in
      psychomotor indicators and MADRS total score (r = 0.4; P < 0.0001). The severity
      of HAM-A total score had no statistically significant correlation with
      psychomotor indicators (P > 0.05). We found that different items of MADRS and HAM
      A correlated with psychomotor disturbances of different strength and
      significance. Objectively, measured psychomotor retardation was associated with
      greater severity of depressive symptoms assessed at the clinical level.
      CONCLUSIONS: Integration between different methods is needed in order to improve
      understanding of the psychopathology and the neurobiology of a disputable
      diagnosis such as clinical depression.

PMID- 23009632
TI  - Cubane-type Mo3FeS4(4+,5+) complexes containing outer diphosphane ligands: ligand
      substitution reactions, spectroscopic studies, and electronic structure.
AB  - A general protocol to access Mo(3)FeS(4)(4+) clusters selectively modified at the
      Fe coordination site is presented starting from the all-chlorine
      Mo(3)(FeCl)S(4)(dmpe)(3)Cl(3) (1) [dmpe = 1,2-bis(dimethylphosphane-ethane)]
      cluster and tetrabutylammonium salts (n-Bu(4)NX) (X = CN(-), N(3)(-), and PhS(
      )). Clusters Mo(3)(FeX)S(4)(dmpe)(3)Cl(3) [X = CN(-) (2), N(3)(-) (3), and PhS(-)
      (4)] are prepared in high yield, and comparison of geometric and redox features
      upon modification of the coordination environment at the Fe site at parity of
      ligands at the Mo sites is also presented. The existence of the cubane-type
      Mo(3)FeS(4)(4+,5+) redox couple is demonstrated by cyclic voltammetry and for
      compound 1 by cluster synthesis and X-ray structure determinations. Ground states
      for the 1/1(+) redox couple are evaluated on the basis of magnetic susceptibility
      measurements, electron paramagnetic resonance, and (57)Fe Mossbauer spectroscopy
      aimed at providing an input of experimental data for electronic structure
      determination based on density functional theory calculations.

PMID- 23009633
TI  - Binding processes determine the stereoselective intestinal and hepatic extraction
      of verapamil in vivo.
AB  - The aim of this study was to investigate the mechanisms that might explain the
      observed route-dependent stereoselective pharmacokinetics (PK) of R/S-verapamil
      (R/S-VER) following oral and intravenous (iv) administration, by using a novel
      pig-specific physiologically based pharmacokinetic (PBPK) model suitable for
      investigations of first-pass extraction in the gut (E(G)) and the liver (E(H)).
      The PBPK model consisted of eight tissue compartments and was designed to
      simultaneously model the plasma concentration-time (PCT) profiles from three
      sampling sites after intrajejunal (ij) or iv administration of VER. The PBPK
      model successfully described the observed PCT profiles and E(H) over time for R-
      and S-VER. Extensive tissue binding to gut mucosa, liver, and lungs was an
      important determinant of the observed PK data. The stereoselective PK of VER was
      explained by a combination of several processes, including enantioselective
      plasma protein binding, blood-to-plasma partition, and gut mucosa and liver
      tissue distribution. The absence of stereoselectivity after iv dosing indicates
      that the first-pass tissue binding effect is an important factor in determining
      the steroselective PK of R/S-VER after oral administration. Additionally a
      combination of extensive liver tissue binding and a metabolite inhibition
      mechanism explained the time-dependent E(H) for both R- and S-VER. An in vitro-in
      vivo correlation of absorption needs to consider these processes because tissue
      binding may confound analysis of a drug's biopharmaceutical properties when using
      classical deconvolution or convolution techniques. In conclusion, a combination
      of PK data from multiple plasma sampling sites and a PBPK modeling approach
      provided a mechanistic understanding of processes involved in the intestinal
      absorption and first-pass extraction of R- and S-VER.

PMID- 23009634
TI  - Functionalization of graphene: covalent and non-covalent approaches, derivatives
      and applications.

PMID- 23009635
TI  - Early risk predictors for impaired numerical skills in 5-year-old children born
      before 32 weeks of gestation.
AB  - AIM: To unravel risk predictors for impaired numerical skills at 5 years of age
      in a population-based cohort of very preterm infants. METHODS: Between January
      2003 and August 2006, we prospectively enrolled all infants born in Tyrol with
      <32 weeks of gestation. A total of 161 of 223 preterm infants (participation rate
      72.2%) had a detailed examination at 5 years of age including cognitive
      assessment (Hannover-Wechsler Intelligence Test for preschool children, third
      edition (HAWIVA-III) or Snijders-Oomen Nonverbal Intelligence Test (SON-R)). In
      135 children, numerical abilities were assessed with the dyscalculia test TEDI
      MATH. The association between pre- and postnatal factors and impaired numerical
      skills was analyzed by means of logistic regression analysis. RESULTS:
      Dyscalculia test showed delayed numerical skills (TEDI-MATH Sum T-score <40) in
      27 of 135 children tested (20.0%). In half of the children tested, delayed
      numerical abilities were related to lower IQ scores. Smoking in pregnancy,
      intracerebral haemorrhage and chronic lung disease were predictive of delayed
      numerical skills at 5 years of age in the multivariate analysis. CONCLUSION: This
      study identified risk predictors for impaired numerical skills in preterm
      infants. Our data support the role of both pre- and perinatal factors in the
      evolution of mathematical deficits.

PMID- 23009636
TI  - Advanced breast cancer-are we doing enough?

PMID- 23009637
TI  - Lumbar posture and trunk muscle activation during a typing task when sitting on a
      novel dynamic ergonomic chair.
AB  - Low back pain (LBP) is a common musculoskeletal disorder and prolonged sitting
      often aggravates LBP. A novel dynamic ergonomic chair ('Back App'), which
      facilitates less hip flexion while sitting on an unstable base has been
      developed. This study compared lumbar posture and trunk muscle activation on this
      novel chair with a standard backless office chair. Twelve painfree participants
      completed a typing task on both chairs. Lumbar posture and trunk muscle
      activation were collected simultaneously and were analysed using paired t-tests.
      Sitting on the novel dynamic chair significantly (p < 0.05) reduced both lumbar
      flexion and the activation of one back muscle (Iliocostalis Lumborum pars
      Thoracis). The discomfort experienced was mild and was similar (p > 0.05) between
      chairs. Maintaining lordosis with less muscle activation during prolonged sitting
      could reduce the fatigue associated with upright sitting postures. Studies with
      longer sitting durations, and in people with LBP, are required. PRACTITIONER
      SUMMARY: Sitting on a novel dynamic chair resulted in less lumbar flexion and
      less back muscle activation than sitting on a standard backless office chair
      during a typing task among pain-free participants. Facilitating lordotic sitting
      with less muscle activation may reduce the fatigue and discomfort often
      associated with lordotic sitting postures.

PMID- 23009638
TI  - Evasion of tumours from the control of the immune system: consequences of brief
      encounters.
AB  - BACKGROUND: In this work a mathematical model describing the growth of a solid
      tumour in the presence of an immune system response is presented. Specifically,
      attention is focused on the interactions between cytotoxic T-lymphocytes (CTLs)
      and tumour cells in a small, avascular multicellular tumour. At this stage of the
      disease the CTLs and the tumour cells are considered to be in a state of dynamic
      equilibrium or cancer dormancy. The precise biochemical and cellular mechanisms
      by which CTLs can control a cancer and keep it in a dormant state are still not
      completely understood from a biological and immunological point of view. The
      mathematical model focuses on the spatio-temporal dynamics of tumour cells,
      immune cells, chemokines and "chemorepellents" in an immunogenic tumour. The CTLs
      and tumour cells are assumed to migrate and interact with each other in such a
      way that lymphocyte-tumour cell complexes are formed. These complexes result in
      either the death of the tumour cells (the normal situation) or the inactivation
      of the lymphocytes and consequently the survival of the tumour cells. In the
      latter case, we assume that each tumour cell that survives its "brief encounter"
      with the CTLs undergoes certain beneficial phenotypic changes. RESULTS: We
      explore the dynamics of the model under these assumptions and show that the
      process of immuno-evasion can arise as a consequence of these encounters. We show
      that the proposed mechanism not only shape the dynamics of the total number of
      tumor cells and of CTLs, but also the dynamics of their spatial distribution. We
      also briefly discuss the evolutionary features of our model, by framing them in
      the recent quasi-Lamarckian theories. CONCLUSIONS: Our findings might have some
      interesting implication of interest for clinical practice. Indeed, immuno-editing
      process can be seen as an "involuntary" antagonistic process acting against
      immunotherapies, which aim at maintaining a tumor in a dormant state, or at
      suppressing it.

PMID- 23009639
TI  - Enantioselective analysis and degradation studies of isocarbophos in soils by
      chiral liquid chromatography-tandem mass spectrometry.
AB  - An enantioselective method is presented for the determination of isocarbophos in
      soil by liquid chromatography coupled with tandem mass spectrometry. The
      pesticide residues in soil samples were extracted with acetonitrile, and complete
      enantioseparation was obtained on an amylose tris(3,5-dimethylphenylcarbamate)
      chiral column using acetonitrile/2 mM ammonium acetate solution containing 0.1%
      formic acid (60:40, v/v) as the mobile phase. The absolute configuration of
      isocarbophos enantiomers was determined by the combination of experimental and
      calculated electronic circular dichroism spectra. The method was utilized to
      investigate the degradation of isocarbophos in soils (Changchun, Hangzhou, and
      Zhengzhou) under sterilized or native conditions. Isocarbophos enantiomers were
      configurationally stable in the selected soils, and the pesticide degradation was
      not enantioselective in the sterilized condition. The degradation behavior of rac
      isocarbophos was different under native conditions, with no enantioselectivity in
      the Changchun soil and with the S-(+)-isocarbophos enriched in the Hangzhou and
      Zhengzhou soils.

PMID- 23009640
TI  - Heat degradation of eukaryotic and bacterial DNA: an experimental model for
      paleomicrobiology.
AB  - BACKGROUND: Theoretical models suggest that DNA degradation would sharply limit
      the PCR-based detection of both eukaryotic and prokaryotic DNA within ancient
      specimens. However, the relative extent of decay of eukaryote and prokaryote DNA
      over time is a matter of debate. In this study, the murine macrophage cell line
      J774, alone or infected with Mycobacterium smegmatis bacteria, were killed after
      exposure to 90 degrees C dry heat for intervals ranging from 1 to 48 h in order
      to compare eukaryotic cells, extracellular bacteria and intracellular bacteria.
      The sizes of the resulting mycobacterial rpoB and murine rpb2 homologous gene
      fragments were then determined by real-time PCR and fluorescent probing.
      FINDINGS: The cycle threshold (Ct) values of PCR-amplified DNA fragments from
      J774 cells and the M. smegmatis negative controls (without heat exposure) varied
      from 26-33 for the J774 rpb2 gene fragments and from 24-29 for M. smegmatis rpoB
      fragments. After 90 degrees C dry heat incubation for up to 48 h, the Ct values
      of test samples increased relative to those of the controls for each amplicon
      size. For each dry heat exposure time, the Ct values of the 146-149-bp fragments
      were lower than those of 746-747-bp fragments. During the 4- to 24-h dry heat
      incubation, the non-infected J774 cell DNA was degraded into 597-bp rpb2
      fragments. After 48 h, however, only 450-bp rpb2 fragments of both non-infected
      and infected J774 cells could be amplified. In contrast, the 746-bp rpoB
      fragments of M. smegmatis DNA could be amplified after the 48-h dry heat exposure
      in all experiments. Infected and non-infected J774 cell DNA was degraded more
      rapidly than M. smegmatis DNA after dry heat exposure (ANOVA test, p < 0.05).
      CONCLUSION: In this study, mycobacterial DNA was more resistant to dry-heat
      stress than eukaryotic DNA. Therefore, the detection of large, experimental,
      ancient mycobacterial DNA fragments is a suitable approach for
      paleomicrobiological studies.

PMID- 23009641
TI  - Synthesis and antifungal activity of new hydrazide derivatives.
AB  - In this study, nine new hydrazide derivatives were synthesized. The reaction of 2
      [(5,6,7,8-tetrahydronaphthalen-2-yl)oxy]acetohydrazide with various benzaldehydes
      or acetophenones resulted in N'-substituted-2-[(5,6,7,8-tetrahydronaphthalen-2
      yl)oxy]acetohydrazide derivatives. The structure elucidation of the synthesized
      and purified compounds was performed by using IR, (1)H-NMR, and FAB(+)-MS
      spectral data and elemental analyses, respectively. Furthermore, the compounds
      were screened and evaluated for their antifungal activity against a panel of
      different human pathogenic Candida strains such as C. albicans, C. glabrata, C.
      utilis, C. tropicalis, C. krusei, C. zeylanoides and C. parapsilosis using agar
      diffusion and broth microdilution assays, respectively. Some of the tested
      compounds showed comparable antifungal activity (MIC = 0.0156->2 mg/mL) with
      ketoconazole.

PMID- 23009642
TI  - Stereospecific positional distribution of fatty acids of Camellia (Camellia
      japonica L.) seed oil.
AB  - The stereospecific positional distribution of fatty acids of camellia seed oil
      (also called camellia oil) was determined. The camellia oil was mainly composed
      of neutral lipids (88.2%), and the oleic acid (86.3%) was found to be a major
      fatty acid of neutral lipids. In the glycolipids and phospholipids, the oleic
      acid was also found to be a major fatty acid at 62.5% and 54.2%, respectively.
      The oleic acid was distributed abundantly in all sn-1, 2, and 3 positions. It was
      found that the oleic acid was present more at sn-2 (93.6%) and 3 positions
      (94.7%), than at sn-1 position (66.0%). Practical Application:  The information
      of stereospecific positional distribution of fatty acids in the camellia oil can
      be used for the development of the structured lipids for food, pharmaceutical,
      and medical purposes.

PMID- 23009643
TI  - Reconstructing the history of a fragmented and heavily exploited red deer
      population using ancient and contemporary DNA.
AB  - BACKGROUND: Red deer (Cervus elaphus) have been an important human resource for
      millennia, experiencing intensive human influence through habitat alterations,
      hunting and translocation of animals. In this study we investigate a time series
      of ancient and contemporary DNA from Norwegian red deer spanning about 7,000
      years. Our main aim was to investigate how increasing agricultural land use,
      hunting pressure and possibly human mediated translocation of animals have
      affected the genetic diversity on a long-term scale. RESULTS: We obtained mtDNA
      (D-loop) sequences from 73 ancient specimens. These show higher genetic diversity
      in ancient compared to extant samples, with the highest diversity preceding the
      onset of agricultural intensification in the Early Iron Age. Using standard
      diversity indices, Bayesian skyline plot and approximate Bayesian computation, we
      detected a population reduction which was more prolonged than, but not as severe
      as, historic documents indicate. There are signs of substantial changes in
      haplotype frequencies primarily due to loss of haplotypes through genetic drift.
      There is no indication of human mediated translocations into the Norwegian
      population. All the Norwegian sequences show a western European origin, from
      which the Norwegian lineage diverged approximately 15,000 years ago. CONCLUSIONS:
      Our results provide direct insight into the effects of increasing habitat
      fragmentation and human hunting pressure on genetic diversity and structure of
      red deer populations. They also shed light on the northward post-glacial
      colonisation process of red deer in Europe and suggest increased precision in
      inferring past demographic events when including both ancient and contemporary
      DNA.

PMID- 23009644
TI  - A case of wedge resection of duodenum for massive gastrointestinal bleeding due
      to duodenal metastasis by renal cell carcinoma.
AB  - BACKGROUND: Gastrointestinal bleeding due to duodenal metastasis from renal cell
      carcinoma is extremely rare. Several previous reports have shown that embolic
      therapy or pancreatoduodenectomy (radical surgical resection) could be effective
      in controlling this type of clinical complication. Management is entirely
      dependent on the general condition and concurrent metastases at other sites.
      Optimizing the therapeutic strategies thus deserves further discussion and
      exploration. METHODS: In this report, we describe a patient with severe co
      morbidities who underwent successful palliative wedge resection of duodenum and
      direct duodenal wall defect repair without reconstruction of duodeno-jejunostomy
      for acute upper digestive tract hemorrhage caused by duodenal metastasis from
      renal clear cell carcinoma. RESULTS: The patient recovered uneventfully and did
      not experience rebleeding and frequent vomiting after surgery. Since then (1.5
      years) he has had no evidence of rebleeding. CONCLUSIONS: Gastrointestinal
      bleeding due to duodenal metastasis of RCC may benefit from emergent resection
      even in the presence of severe co-morbidities, and for palliative treatment.

PMID- 23009645
TI  - The risk of maternal obesity to the long-term health of the offspring.
AB  - The prevalence of maternal obesity has risen dramatically in recent years, with
      approximately one in five pregnant women in the UK now classed as obese (body
      mass index >= 30 kg/m(2) ) at antenatal booking. Obesity during pregnancy has
      been hypothesized to exert long-term health effects on the developing child
      through 'early life programming'. While this phenomenon has been well studied in
      a maternal undernutrition paradigm, the processes by which the programming
      effects of maternal obesity are mediated are less well understood. In humans,
      maternal obesity has been associated with a number of long-term adverse health
      outcomes in the offspring, including lifelong risk of obesity and metabolic
      dysregulation with increased insulin resistance, hypertension and dyslipidaemia,
      as well as behavioural problems and risk of asthma. The complex relationships
      between the maternal metabolic milieu and the developing foetus, as well as the
      potential influence of postnatal lifestyle and environment, have complicated
      efforts to study the programming effects of maternal overnutrition in humans.
      This review will examine the emerging evidence from human studies linking
      maternal obesity to adverse offspring outcomes.

PMID- 23009646
TI  - Illegal gene flow from transgenic creeping bentgrass: the saga continues.
AB  - Ecologists have paid close attention to environmental effects that fitness
      enhancing transgenes might have following crop-to-wild gene flow (e.g. Snow et
      al. 2003). For some crops, gene flow also can lead to legal problems,especially
      when government agencies have not approved transgenic events for unrestricted
      environmental release.Creeping bentgrass (Agrostis stolonifera), a common turf
      grass used in golf courses, is the focus of both areas of concern. In 2002, prior
      to expected deregulation (still pending), The Scotts Company planted creeping
      bentgrass with transgenic resistance to the herbicide glyphosate,also known as
      RoundUp, on 162 ha in a designated control area in central Oregon (Fig.
      1).Despite efforts to restrict gene flow, wind-dispersed pollen carried
      transgenes to florets of local A. stolonifera and A. gigantea as far as 14 km
      away, and to sentinel plants placed as far as 21 km away (Watrud et al.
      2004).Then, in August 2003, a strong wind event moved transgenic seeds from wind
      rows of cut bentgrass into nearby areas. The company's efforts to kill all
      transgenic survivors in the area failed: feral glyphosate-resistant populations
      of A. stolonifera were found by Reichman et al.(2006), and 62% of 585 bentgrass
      plants had the telltale CP4 EPSPS transgene in 2006 (Zapiola et al. 2008; Fig.
      2).Now, in this issue, the story gets even more interesting as Zapiola & Mallory
      Smith (2012) describe a transgenic,intergeneric hybrid produced on a feral,
      transgenic creeping bentgrass plant that received pollen from Polypogon
      monspeliensis (rabbitfoot grass). Their finding raises a host of new questions
      about the prevalence and fitness of intergeneric hybrids, as well as how to
      evaluate the full extent of gene flow from transgenic crops.

PMID- 23009647
TI  - Transcriptomic insights into mechanisms of symbiotic cooperation.
AB  - Intraspecific genetic variation can affect community structure and ecosystem
      processes (Bolnick et al. 2011). It can also influence phenotypic expression by
      genotypes within other species to produce genotype-by-genotype (G * G)
      interaction (Falconer & Mackay 1996). Evolution of one species drives correlated
      evolution of others when it causes G * G for fitness (Thompson 2005). However,
      the mechanisms by which species interact also influence evolutionary outcomes
      (Kummel & Salant 2006; Golubski & Klausmeier 2010; Akcay & Simms 2011; Grman et
      al. 2012). To identify genes and putative functional mechanisms underlying G * G
      interactions, Heath et al. (2012) analysed natural variation in the symbiotic
      transcriptome of the mutualistic nutritional symbiosis between a legume host
      Medicago truncatula and the facultative endosymbiotic rhizobium Sinorhizobium
      meliloti. Using twelve microarrays, the authors simultaneously measured host and
      symbiont gene expression in root nodules from four factorial pairings of host and
      symbiont genotypes that produced G * G in host fitness (Fig. 1, upper panel).
      Rhizobium gene expression was influenced by rhizobium and plant genotype and the
      G * G interaction (Fig. 1, lower panel), whereas plant gene expression was
      influenced primarily by plant genotype. The authors identified rhizobium genes
      that might contribute to G * G in host plant fitness. Heath et al. (2012) have
      moved beyond the constraints of single organism analysis towards a more realistic
      understanding of plants and bacteria as organisms inextricably linked with
      symbioses that affect even basic patterns of gene expression.

PMID- 23009648
TI  - Invasion of the hybrids.
AB  - Human activity and climate change are increasingly driving species, which were
      once separate together, leading to the potential for gene flow. Hybridization
      between diverged species brings together two genomes which have evolved to meet
      different adaptive requirements. The unique combination of these traits in a
      hybrid may be beneficial or maladaptive, but either way it results in increased
      phenotypic variation. A percentage of hybrid individuals may, therefore, find
      themselves able to exploit environmental niches which their progenitors cannot,
      leading to invasive hybrid swarms becoming established in new habitats. Previous
      research into hybrids, most famously that of Loren Rieseberg and co-workers
      (Rieseberg et al. 1999, 2003) in sunflowers, demonstrated that hybridization can
      give rise to transgressive segregation of adaptive traits, wherein the
      combination of favourable alleles from both parents in hybrids can enable them to
      outperform either. However, the question still remains as to how much of the
      competitive ability of hybrids is a direct result of admixture and how much is
      the result of selection after the fact. In this issue of Molecular Ecology,
      (Czypionka et al. 2012) describe their study of transcriptional changes resulting
      from hybridization in a fish hybrid termed invasive sculpins (Cottus). Using gene
      expression microarray assays, they compare gene expression in both wild and lab
      reared invasive hybrids to the progenitor species and experimentally produced
      F(2)  hybrids. They demonstrate that whilst hybridization alone does result in
      higher variance in gene expression (some of which is transgressive), many of the
      transgressive changes distinguishing the invasives appear to have come about
      subsequent to the initial natural hybridization event. They speculate that
      initial success of the hybrids in their new habitat is facilitated by
      hybridization, but that optimization of the invasive phenotype and removal of
      maladaptive traits rapidly reduces the variation in gene expression seen in early
      hybrids.

PMID- 23009649
TI  - Playing the numbers: how hepatitis C patients create meaning and make healthcare
      decisions from medical test results.
AB  - In this article we describe how patients assign meanings to medical test results
      and use these meanings to justify their actions. Evidence is presented from lay
      interpretations of medical tests for monitoring hepatitis C viral infection (HCV)
      to show how numeracy becomes embodied in the absence of physical symptoms.
      Illness narratives from 307 individuals infected with HCV were collected from the
      internet and analysed qualitatively. As part of standard medical care,
      chronically infected HCV patients are required to have periodic blood tests for
      laboratory testing. The lab results are presented numerically and compared with
      established physiological standards. HCV patients' knowledge and interpretations
      of test results have important consequences for their health behaviour and their
      medical decisions. In their stories, the patients described their decisions to
      begin, delay or stop treatment and developed strategies to alter their diet,
      exercise and use alternative therapies according to changes in their test result.
      The perceived meanings of test results are powerful signifiers that are capable
      of altering the course of HCV patients' illness, lives and stories. An
      interpretive model of health numeracy has the advantage of promoting
      understanding between patients and healthcare providers over a model that views
      innumeracy as a skill deficit.

PMID- 23009650
TI  - Reducing young driver crash casualties in Great Britain - use of routine police
      crash data to estimate the potential benefits of graduated driver licensing.
AB  - Crashes involving young drivers (YD) cause significant morbidity and mortality in
      Great Britain (GB). Graduated Driver Licensing (GDL) is used in some countries to
      address this. This study assessed potential casualty and cost savings of possible
      GDL programmes in GB. Police road crash data were analysed to identify YD crashes
      at night or while carrying passengers. These data were then used to estimate the
      potential effects of GDL. 314,561 casualties and 3469 fatalities occurred in YD
      crashes. 25.1% of YD crashes occurred between 9 pm and 6 am and 24.4% occurred
      with a 15- to 24-year old passenger in the car. A 'strict' form of GDL in GB
      (night time restriction 9 pm-6 am, no 15-24 year old passengers) with 50%
      compliance would prevent 114 deaths and 872 serious casualties each year. The
      estimated value of prevention is L424M pa. A 'less strict' form of GDL (night
      time restriction 10 pm-5 am, maximum of one 15-19 year old passenger) with 50%
      compliance would prevent 81 deaths and 538 serious injuries. The estimated value
      of prevention is L273M pa. Implementing GDL in GB could save significant numbers
      of lives. Public health organisations have a duty to advocate for such
      legislation. 

PMID- 23009651
TI  - Molecular analysis of model gut microbiotas by imaging mass spectrometry and
      nanodesorption electrospray ionization reveals dietary metabolite
      transformations.
AB  - The communities constituting our microbiotas are emerging as mediators of the
      health-disease continuum. However, deciphering the functional impact of microbial
      communities on host pathophysiology represents a formidable challenge, due to the
      heterogeneous distribution of chemical and microbial species within the
      gastrointestinal (GI) tract. Herein, we apply imaging mass spectrometry (IMS) to
      localize metabolites from the interaction between the host and colonizing
      microbiota. This approach complements other molecular imaging methodologies in
      that analytes need not be known a priori, offering the possibility of untargeted
      analysis. Localized molecules within the GI tract were then identified in situ by
      surface sampling with nanodesorption electrospray ionization Fourier transform
      ion cyclotron resonance-mass spectrometry (nanoDESI FTICR-MS). Products from
      diverse structural classes were identified including cholesterol-derived lipids,
      glycans, and polar metabolites. Specific chemical transformations performed by
      the microbiota were validated with bacteria in culture. This study illustrates
      how untargeted spatial characterization of metabolites can be applied to the
      molecular dissection of complex biology in situ.

PMID- 23009652
TI  - A new non-invasive approach based on polyhexamethylene biguanide increases the
      regression rate of HPV infection.
AB  - BACKGROUND: HPV infection is a worldwide problem strictly linked to the
      development of cervical cancer. Persistence of the infection is one of the main
      factors responsible for the invasive progression and women diagnosed with
      intraepithelial squamous lesions are referred for further assessment and surgical
      treatments which are prone to complications. Despite this, there are several
      reports on the spontaneous regression of the infection.This study was carried out
      to evaluate the effectiveness of a long term polyhexamethylene biguanide (PHMB)
      based local treatment in improving the viral clearance, reducing the time
      exposure to the infection and avoiding the complications associated with the
      invasive treatments currently available. METHOD: 100 women diagnosed with HPV
      infection were randomly assigned to receive six months of treatment with a PHMB
      based gynecological solution (Monogin(r), Lo.Li. Pharma, Rome - Italy) or to
      remain untreated for the same period of time. RESULTS: A greater number of
      patients, who received the treatment were cleared of the infection at the two
      time points of the study (three and six months) compared to that of the control
      group. A significant difference in the regression rate (90% Monogin group vs 70%
      control group) was observed at the end of the study highlighting the time
      dependent ability of PHMB to interact with the infection progression.
      CONCLUSIONS: The topic treatment with PHMB is a preliminary safe and promising
      approach for patients with detected HPV infection increasing the chance of
      clearance and avoiding the use of invasive treatments when not strictly
      necessary. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01571141.

PMID- 23009653
TI  - Interactive associations of drug-drug and drug-drug-drug with IIA subdomain of
      human serum albumin.
AB  - Owing to advantageous biochemical and pharmacological properties of human serum
      albumin (HSA), HSA-based drug carrier is playing an increasing role in the
      clinical setting. Since the IIA subdomain of HSA is a big hydrophobic cavity, we
      proposed that HSA delivers multiple drugs simultaneously docking on the IIA
      subdomain and that drugs may influence each other's binding affinity to albumin
      when cobinding the HSA IIA subdomain. Therefore, we studied the interactive
      association of drugs with the IIA subdomain of HSA by fluorescence spectroscopy
      and X-ray crystallography, in order to elucidate the molecular mechanism and
      behavior of drugs cobinding the IIA subdomain of HSA, and develop a universal
      structure-based model for HSA carrier design. We solved HSA-fatty acid-cinnamic
      acid, HSA-fatty acid-cinnamic acid-indometacin and HSA-fatty acid-cinnamic acid
      indometacin-lamivudine complex structures, respectively. HSA complex structures
      and fluorescence quenching of HSA revealed that different drugs can regulate
      binding sites, binding mode and binding affinity of each other. For example,
      indometacin renders cinnamic acid to make reposition, and decreases binding
      affinity of HSA for cinnamic acid, but increases binding affinity of itself to
      HSA. Lamivudine makes cinnamic acid and indometacin to bind new subsites.
      Cinnamic acid-indometacin enhances binding affinity of lamivudine, and cinnamic
      acid-lamivudine increases binding affinity of indometacin, but indometacin
      lamivudine decreases binding affinity of cinnamic acid to HSA. The study provided
      a biochemical basis for structure-guided development of HSA delivery system.

PMID- 23009654
TI  - Is baseline bone imaging in high-risk breast cancer patients justified?

PMID- 23009655
TI  - Throwing caution to the wind: callous-unemotional traits and risk taking in
      adolescents.
AB  - Developmental research suggests that adolescents may be highly influenced by
      their peers to take risks. Although youths with callous-unemotional (CU) traits
      engage in high-risk behaviors in the form of antisocial behavior and aggression,
      little is known about their decision making, particularly when their peers are
      present. Youths high on CU traits may be most susceptible to influence,
      especially when rewards are involved, or they may be highly rational relative to
      their low CU peers and less susceptible to social peer pressures. The present
      study used a gambling task with 675 youths (female n = 348), ages 16 to 20 years
      (M = 16.9, SD = .8). The majority were White British (64%). We experimentally
      manipulated whether youths made decisions in groups with peers or individually.
      All members of the group reported on their CU traits. Using multilevel modeling
      to control for group-level effects, youths with higher levels of CU traits were
      found to be less sensitive to accruing rewards on the gambling task than youths
      low on these traits. When in groups, male participants with higher levels of CU
      traits made quicker decisions to take risks than male participants lower on CU
      traits, particularly after punishment. Youths with CU traits are distinct in
      showing a lack of emotion and this may facilitate heightened rationality in
      responding to rewards. However, results suggest that male adolescents who are
      high on CU traits may react to the possible frustration of losing by attempting
      to gain back rewards quickly when their peers are watching.

PMID- 23009656
TI  - Structural and energetic properties of closed shell XF(n) (X = Cl, Br, and I; n =
      1-7) and XO(n)F(m) (X = Cl, Br, and I; n = 1-3; m = 0-6) molecules and ions
      leading to stability predictions for yet unknown compounds.
AB  - Atomization energies at 0 K and heats of formation at 0 and 298 K were predicted
      for the closed shell compounds XF, XF(2)(-), XF(2)(+), XF(3), XF(4)(-), XF(4)(+),
      XF(5), XF(6)(-), XF(6)(+) (X = Cl and Br) and XO(+), XOF, XOF(2)(-), XOF(2)(+),
      XOF(3), XOF(4)(-), XOF(4)(+), XOF(5), XOF(6)(-), XO(2)(+), XO(2)F, XO(2)F(2)(-),
      XO(2)F(2)(+), XO(2)F(3), XO(2)F(4)(-), XO(3)(+), XO(3)F, XO(3)F(2)(-) (X = Cl,
      Br, and I) using a composite electronic structure approach based on coupled
      cluster CCSD(T) calculations extrapolated to the complete basis set limit with
      additional corrections. The calculated heats of formation are in good agreement
      with the available experimental data. The calculated heats of formation were used
      to predict fluoride affinities, fluorine cation affinities, and F(2) binding
      energies. On the basis of our results, BrOF(5) and BrO(2)F(3) are predicted to be
      stable against spontaneous loss of F(2) and should be able to be synthesized,
      whereas BrF(7), ClF(7), BrOF(6)(-), and ClOF(6)(-) are unstable by a very wide
      margin. The stability of ClOF(5) is a borderline case. Although its F(2) loss is
      predicted to be exothermic by 4.4 kcal/mol, it may have a sufficiently large
      barrier toward decomposition and be preparable. This situation would resemble
      ClO(2)F(3) which was successfully synthesized in spite of being unstable toward
      F(2) loss by 3.3 kcal/mol. On the other hand, the ClOF(4)(+) and BrOF(4)(+)
      cations are less likely to be preparable with F(2) loss exothermicities of -17.5
      and -9.3 kcal/mol, respectively. On the basis of the F(-) affinities of ClOF
      (45.4 kcal/mol), BrOF (58.7 kcal/mol), and BrO(2)F(3) (65.7 kcal/mol) and their
      predicted stabilities against loss of F(2), the ClOF(2)(-), BrOF(2)(-), and
      BrO(2)F(4)(-) anions are excellent targets for synthesis. Our previous failure to
      prepare the ClO(2)F(4)(-) anion can be rationalized by the predicted high
      exothermicity of -17.4 kcal/mol for the loss of F(2).

PMID- 23009657
TI  - Association of maternal scaffolding to maternal education and cognition in
      toddlers born preterm and full term.
AB  - AIM: Parental behaviour described as 'scaffolding' has been shown to influence
      outcomes in at-risk children. The purpose of this study was to compare maternal
      verbal scaffolding in toddlers born preterm and full term. METHODS: The
      scaffolding behaviour of mothers of toddlers born preterm and healthy full term
      was compared during a 5-min videotaped free play session with standardized toys.
      We compared two types of scaffolding and their associations with socio
      demographic, neonatal medical factors and cognition. RESULTS: The mothers of
      toddlers born full term used more complex scaffolding. Maternal education was
      associated with complex scaffolding scores for the preterm children only.
      Specifically, the preterm children who were sicker in the neonatal period, and
      whose mothers had higher education, used more complex scaffolding. In addition,
      children born preterm, who had less days of ventilation, had higher cognitive
      scores when their mothers used more complex scaffolding. Similarly, cognitive and
      scaffolding scores were higher for children born full term. CONCLUSION: Our
      findings highlight early differences in mother-child interactive styles of
      toddlers born preterm compared with full term. Teaching parents play methods that
      support early problem-solving skills may support a child's method of exploration
      and simultaneously their language development.

PMID- 23009658
TI  - The AAA ATPase VPS4/SKD1 regulates endosomal cholesterol trafficking
      independently of ESCRT-III.
AB  - The exit of low-density lipoprotein derived cholesterol (LDL-C) from late
      endosomes (LE)/lysosomes (Ly) is mediated by Niemann-Pick C1 (NPC1), a multipass
      integral membrane protein on the limiting membranes of LE/Ly, and by NPC2, a
      cholesterol-binding protein in the lumen of LE/Ly. NPC2 delivers cholesterol to
      the N-terminal domain of NPC1, which is believed to insert cholesterol into the
      limiting membrane for subsequent transport to other subcellular organelles. Few
      cytoplasmic factors have been identified to govern cholesterol efflux from LE/Ly,
      and much less is known about the underlying molecular mechanisms. Here we
      establish VPS4, an AAA ATPase that has a well-established role in disassembling
      the ESCRT (endosomal sorting complex required for transport)-III polymer, as an
      important regulator of endosomal cholesterol transport. Knocking down VPS4 in
      HeLa cells resulted in prominent accumulation of LDL-C in LE/Ly, and disrupted
      cholesterol homeostatic responses at the endoplasmic reticulum. The level and
      localization of NPC1 and NPC2 appeared to be normal in VPS4 knockdown cells.
      Importantly, depleting any of the ESCRT-III components did not exert a
      significant effect on endosomal cholesterol transport. Our results thus identify
      an important cytoplasmic regulator of endosomal cholesterol trafficking and
      represent the first functional separation of VPS4 from ESCRT-III.

PMID- 23009659
TI  - An experimental investigation on the requirement of roof height and sill width
      for car ingress and egress.
AB  - This study aimed at experimentally investigating the influence of roof height and
      sill width on car ingress/egress movements. The first uncomfortable (Ht1) and the
      lowest acceptable (Ht2) roof heights were obtained from 26 participants of three
      different stature groups thanks to a multi-adjustable vehicle mock-up. Both Ht1
      and Ht2 were affected neither by stature nor by vehicle type. Only a difference
      of 45 mm between Ht1 and Ht2 was observed. Tall volunteers more flexed the trunk
      and neck than short persons thanks to a larger space available around the seat
      when the head passing under the roof. The vehicle type had almost no effect on
      upper body posture. The roof height only affected neck flexion. The sill width
      mainly imposed a lateral translation. Results demonstrated that an appropriate
      roof height should be determined carefully. A small change of 45 mm in roof
      height may lead to an unacceptable situation. PRACTITIONER SUMMARY: The present
      study experimentally investigated the effects of roof height and sill width on
      car ingress and egress movements. Short females required almost the same roof
      height as tall males due to smaller space around the seat. The results would help
      to optimise car dimensions for improving car accessibility.

PMID- 23009660
TI  - Structure-activity relationships of bergenin derivatives effect on alpha
      glucosidase inhibition.
AB  - The alpha-glucosidase inhibitory activities of bergenin derivatives were
      evaluated. Bergenin derivatives were synthesized from bergenin which is a
      characteristic compound of B. ligulata. A new bergenin derivative, 11-O-(3',4'
      dimethoxybenzoyl)-bergenin showed the highest potent inhibitory activity among
      those of bergenin derivatives. The presence of substituents at 3',4'-position in
      bergenin derivatives altered the alpha-glucosidase inhibitory activity. 11-O
      (3',4'-dimethoxybenzoyl)-bergenin was noncompetitive inhibitor for alpha
      glucosidase. The present study reveals that bergenin derivatives could be
      classified as a new group of alpha-glucosidase inhibitors. 

PMID- 23009661
TI  - Surviving in a toxic world: transcriptomics and gene expression profiling in
      response to environmental pollution in the critically endangered European eel.
AB  - BACKGROUND: Genomic and transcriptomic approaches have the potential for
      unveiling the genome-wide response to environmental perturbations. The abundance
      of the catadromous European eel (Anguilla anguilla) stock has been declining
      since the 1980s probably due to a combination of anthropogenic and climatic
      factors. In this paper, we explore the transcriptomic dynamics between
      individuals from high (river Tiber, Italy) and low pollution (lake Bolsena,
      Italy) environments, which were measured for 36 PCBs, several organochlorine
      pesticides and brominated flame retardants and nine metals. RESULTS: To this end,
      we first (i) updated the European eel transcriptome using deep sequencing data
      with a total of 640,040 reads assembled into 44,896 contigs (Eeelbase release
      2.0), and (ii) developed a transcriptomic platform for global gene expression
      profiling in the critically endangered European eel of about 15,000 annotated
      contigs, which was applied to detect differentially expressed genes between
      polluted sites. Several detoxification genes related to metabolism of pollutants
      were upregulated in the highly polluted site, including genes that take part in
      phase I of the xenobiotic metabolism (CYP3A), phase II (glutathione-S
      transferase) and oxidative stress (glutathione peroxidase). In addition, key
      genes in the mitochondrial respiratory chain and oxidative phosphorylation were
      down-regulated at the Tiber site relative to the Bolsena site. CONCLUSIONS:
      Together with the induced high expression of detoxification genes, the suggested
      lowered expression of genes supposedly involved in metabolism suggests that
      pollution may also be associated with decreased respiratory and energy
      production.

PMID- 23009662
TI  - Methods of improving speech intelligibility for listeners with hearing resolution
      deficit.
AB  - Methods developed for real-time time scale modification (TSM) of speech signal
      are presented. They are based on the non-uniform, speech rate depended SOLA
      algorithm (Synchronous Overlap and Add). Influence of the proposed method on the
      intelligibility of speech was investigated for two separate groups of listeners,
      i.e. hearing impaired children and elderly listeners. It was shown that for the
      speech with average rate equal to or higher than 6.48 vowels/s, all of the
      proposed methods have statistically significant impact on the improvement of
      speech intelligibility for hearing impaired children with reduced hearing
      resolution and one of the proposed methods significantly improves comprehension
      of speech in the group of elderly listeners with reduced hearing resolution.
      VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2065486371761991.

PMID- 23009663
TI  - Stress associated gene expression in blood cells is related to outcome in
      radiotherapy treated head and neck cancer patients.
AB  - BACKGROUND: We previously observed that a radiotherapy-induced biochemical
      response in plasma was associated with favourable outcome in head and neck
      squamous carcinoma cancer (HNSCC) patients. The aim of the present study was to
      compare stress associated blood cell gene expression between two sub-groups of
      HNSCC patients with different biochemical responses to radiotherapy. METHODS: Out
      of 87 patients (histologically verified), 10 biochemical 'responders' having a
      high relative increase in plasma oxidative damage and a concomitant decrease in
      plasma antioxidants during radiotherapy and 10 'poor-responders' were selected
      for gene-expression analysis and compared using gene set enrichment analysis.
      RESULTS: There was a significant induction of stress-relevant gene-sets in the
      responders following radiotherapy compared to the poor-responders. The relevance
      of the involvement of similar stress associated gene expression for HNSCC cancer
      and radioresistance was verified using two publicly available data sets of 42
      HNSCC cases and 14 controls (GEO GSE6791), and radiation resistant and radiation
      sensitive HNSCC xenografts (E-GEOD-9716). CONCLUSIONS: Radiotherapy induces a
      systemic stress response, as revealed by induction of stress relevant gene
      expression in blood cells, which is associated to favourable outcome in a cohort
      of 87 HNSCC patients. Whether these changes in gene expression reflects a
      systemic effect or are biomarkers of the tumour micro-environmental status needs
      further study. TRIAL REGISTRATION: Raw data are available at ArrayExpress under
      accession number E-MEXP-2460.

PMID- 23009664
TI  - Identification and characterization of D410E, a novel mutation in the loop 3
      domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach
      using a novel calcilytic, AXT914.
AB  - OBJECTIVE: Activating mutations of the calcium-sensing receptor (CASR) gene are
      associated with autosomal dominant hypocalcemia (ADH) characterized by benign
      hypocalcemia, inappropriately low (PTH) levels and mostly hypercalciuria. Herein,
      we report a novel activating mutation in the CASR gene in a Korean family with
      ADH. METHOD: The CASR gene was sequenced in the patient with ADH. The identified
      mutations were also evaluated in the patient's family members by PCR-based
      sequencing. For functional studies, we examined phosphorylation of ERK1/2. In
      addition, intracellular Ca(2+) mobilization and the effects of the calcilytic,
      AXT914 were measured using fluorophore Fura-2 dye. RESULT: Direct sequencing
      analysis of the CASR gene showed that the proband and her daughter possess a
      novel mutation c.1230T>A, resulting in a D410E missense mutation on exon 4 of the
      CASR gene. Escalation of the extracellular Ca(2+) concentration resulted in
      stronger phosphorylation of ERK1/2 and higher levels of intracellular Ca(2+) in
      HEK293 cells expressing mutant CASR, compared with wild-type CASR. The increase
      in intracellular Ca(2+) signalling via CASR was successively blunted by treatment
      with AXT914. CONCLUSIONS: Over 60 activating mutations in the CASR gene have been
      identified to cause ADH so far. Here, we add one more activating mutation that
      causes ADH. The novel activating mutation (D410E) occurred in the loop 3 region
      of CASR, where its function was believed to be of little importance; therefore,
      this mutation may be of interest. Further clinical study will be needed to
      validate the effectiveness of calcilytics in treatment of ADH in vivo.

PMID- 23009665
TI  - Effect of UK policy on medical migration: a time series analysis of physician
      registration data.
AB  - BACKGROUND: Economically developed countries have recruited large numbers of
      overseas health workers to fill domestic shortages. Recognition of the negative
      impact this can have on health care in developing countries led the United
      Kingdom Department of Health to issue a Code of Practice for National Health
      Service (NHS) employers in 1999 providing ethical guidance on international
      recruitment. Case reports suggest this guidance had limited influence in the
      context of other NHS policy priorities. METHODS: The temporal association between
      trends in new professional registrations from doctors qualifying overseas and
      relevant United Kingdom government policy is reported. Government policy
      documents were identified by a literature review; further information was
      obtained, when appropriate, through requests made under the Freedom of
      Information Act. Data on new professional registration of doctors were obtained
      from the General Medical Council (GMC). RESULTS: New United Kingdom professional
      registrations by doctors trained in Africa and south Asia more than doubled from
      3105 in 2001 to 7343 in 2003, as NHS Trusts sought to achieve recruitment targets
      specified in the 2000 NHS Plan; this occurred despite ethical guidance to avoid
      active recruitment of doctors from resource-poor countries. Registration of such
      doctors declined subsequently, but in response to other government policy
      initiatives. A fall in registration of South African-trained doctors from 3206 in
      2003 to 4 in 2004 followed a Memorandum of Understanding with South Africa signed
      in 2003. Registrations from India and Pakistan fell from a peak of 4626 in 2004
      to 1169 in 2007 following changes in United Kingdom immigration law in 2005 and
      2006. Since 2007, registration of new doctors trained outside the European
      Economic Area has remained relatively stable, but in 2010 the United Kingdom
      still registered 722 new doctors trained in Africa and 1207 trained in India and
      Pakistan. CONCLUSIONS: Ethical guidance was ineffective in preventing mass
      registration by doctors trained in resource-poor countries between 2001 and 2004
      because of competing NHS policy priorities. Changes in United Kingdom immigration
      laws and bilateral agreements have subsequently reduced new registrations, but
      about 4000 new doctors a year continue to register who trained in Africa, Asia
      and less economically developed European countries.

PMID- 23009666
TI  - Atomistic description of electron beam damage in nitrogen-doped graphene and
      single-walled carbon nanotubes.
AB  - By combining ab initio simulations with state-of-the-art electron microscopy and
      electron energy loss spectroscopy, we study the mechanism of electron beam damage
      in nitrogen-doped graphene and carbon nanotubes. Our results show that the
      incorporation of nitrogen atoms results in noticeable knock-on damage in these
      structures already at an acceleration voltage of 80 kV, at which essentially no
      damage is created in pristine structures at corresponding doses. Contrary to an
      early estimate predicting rapid destruction via sputtering of the nitrogen atoms,
      in the case of substitutional doping, damage is initiated by displacement of
      carbon atoms neighboring the nitrogen dopant, leading to the conversion of
      substitutional dopant sites into pyridinic ones. Although such events are
      relatively rare at 80 kV, they become significant at higher voltages typically
      used in electron energy loss spectroscopy studies. Correspondingly, we measured
      an energy loss spectrum time series at 100 kV that provides direct evidence for
      such conversions in nitrogen-doped single-walled carbon nanotubes, in excellent
      agreement with our theoretical prediction. Besides providing an improved
      understanding of the irradiation stability of these structures, we show that
      structural changes cannot be neglected in their characterization employing high
      energy electrons.

PMID- 23009667
TI  - Prevalence of overweight and obesity in preschool children (2-5 year-olds) in
      Birjand, Iran.
AB  - BACKGROUND: Childhood overweight and obesity have increased progressively in
      developing countries and nowadays they are considered as a global epidemic.The
      aim of the present study was to determine prevalence of overweight and obesity in
      2-5 year-old children in kindergartens of Birjand in 2008. FINDINGS: This cross-
      sectional and descriptive- analytical study was conducted on 500 children, who
      were 2-5 years-old, in kindergartens of Birjand selected through census. It was
      found that prevalence of overweight was 10.6% (11.7% in females and 9.6% in
      males) and obesity 7.6% (6.3% in females and 9.6% in males). Prevalence of
      overweight and obesity were statistically significant regarding birth weight,
      mother's occupation and father's level of education. CONCLUSION: Prevalence of
      overweight and obesity in pre-schoolchildren is more than that of 7-18 year-old
      group in Birjand, but it is less than the result of similar studies in Tehran and
      most studies in other countries. Further studies are recommended to identify risk
      factors in obese children. Periodic studies are necessary to compare the changes
      in prevalence of obesity in children in future.

PMID- 23009668
TI  - Direct observation and control of ultrafast photoinduced twisted intramolecular
      charge transfer (TICT) in triphenyl-methane dyes.
AB  - Femtosecond time-resolved infrared spectroscopy was employed to study
      intramolecular charge transfer in triphenylmethane dyes, including malachite
      green (MG), malachite green carbinol base (MGCB), and leucomalachite green (LMG).
      A local excited state (LE) and a twisted intramolecular charge-transfer (TICT)
      state have been observed directly in MG. Furthermore, solvent-controlled TICT
      measurements in a series of linear alcohols indicate that the transition time (4
      11 ps) from LE to TICT is strongly dependent on alcohol viscosity, which is due
      to rotational hindrance of dimethylaniline in high-viscosity solvents. For LMG,
      no TICT is observed due to steric hindrance caused by the sp(3)-hybridized
      central carbon atom. However, for MGCB, TICT is rescued by the addition of the
      electron-donating hydroxyl group to the bridge. These results for MG and its
      analogues provide new insight regarding the dynamics and mechanism of twisted
      intramolecular charge transfer (TICT) in triphenylmethane dyes.

PMID- 23009669
TI  - Physicochemical, microstructural, and antibacterial properties of beta-chitosan
      and kudzu starch composite films.
AB  - This study investigated physicochemical, microstructural, and antibacterial
      properties of beta-chitosan-kudzu starch composite films with addition of 0%,
      20%, 60%, or 100% kudzu starch (w starch/w chitosan) in 1% chitosan solution.
      Molecular interactions between chitosan and kudzu starch and the crystal
      structure of the films were also determined. Adding 60% kudzu starch reduced
      water vapor permeability and solubility of pure beta-chitosan film by about 15%
      and 20%, respectively, whereas mechanical strength and flexibility of the film
      were increased about 50% and 25%, respectively. Micrograph showed that beta
      chitosan film was totally amorphous, and the composite films generally became
      rougher with more starch added. Fourier transform infrared and X-ray diffraction
      spectra showed that the 2 film-forming components were compatible with each
      other. Pure beta-chitosan film resulted in 9.5 and 11.5 log CFU/mL reduction in
      Escherichia coli and Listeria innocua based on plate count method, respectively.
      Addition of kudzu starch reduced the antibacterial activity of film, but still
      achieved 8.3 and 10.3 log CFU/mL reduction in E. coli and L. innocua,
      respectively when kudzu starch to chitosan weight ratio was 1:1. Reduced
      antibacterial activity might attribute to the interaction of amino groups in beta
      chitosan with the hydroxyl groups in kudzu starch. This study demonstrated that
      kudzu starch effectively improved water barrier of beta-chitosan film, and the
      composite films retained strong antibacterial ability. PRACTICAL APPLICATION: One
      percent of beta-chitosan containing 60% kudzu starch (w/w chitosan) composite
      films possessed better mechanical and water barrier properties than pure beta
      chitosan films, and showed strong antibacterial activity against both Gram
      positive and Gram-negative bacteria. The films may be used as wraps or coatings
      to prolong the shelf life of different foods or other similar applications.

PMID- 23009671
TI  - A retrospective mathematical analysis of controlled release design and
      experimentation.
AB  - The development and performance evaluation of new biodegradable polymer
      controlled release formulations relies on successful interpretation and
      evaluation of in vitro release data. However, depending upon the extent of
      empirical characterization, release data may be open to more than one qualitative
      interpretation. In this work, a predictive model for release from degradable
      polymer matrices was applied to a number of published release data in order to
      extend the characterization of release behavior. Where possible, the model was
      also used to interpolate and extrapolate upon collected released data to clarify
      the overall duration of release and also kinetics of release between widely
      spaced data points. In each case examined, mathematical predictions of release
      coincide well with experimental results, offering a more definitive description
      of each formulation's performance than was previously available. This information
      may prove particularly helpful in the design of future studies, such as when
      calculating proper dosing levels or determining experimental end points in order
      to more comprehensively evaluate a controlled release system's performance.

PMID- 23009672
TI  - A randomised controlled trial of the Home Independence Program, an Australian
      restorative home-care programme for older adults.
AB  - A randomised controlled trial was conducted to test the effectiveness of the Home
      Independence Program (HIP), a restorative home-care programme for older adults,
      in reducing the need for ongoing services. Between June 2005 and August 2007, 750
      older adults referred to a home-care service for assistance with their personal
      care participated in the study and received HIP or 'usual' home-care services.
      Service outcomes were compared at 3 and 12 months. Subgroups of 150 from each
      group were also compared on functional and quality of life measures. Data were
      analysed by 'intention-to-treat' and 'as-treated'. The intention-to-treat
      analysis showed at 3 and 12 months that the HIP group was significantly less
      likely to need ongoing personal care [Odds ratio (OR) = 0.18, 95% CI = 0.13-0.26,
      P < 0.001; OR = 0.22, 95% CI = 0.15-0.32, P < 0.001]. Both subgroups showed
      improvements on the individual outcome measures over time with the only
      significant differences being found at 12 months for Instrumental Activities of
      Daily Living (IADL) in the as-treated analysis. Contamination of the control
      group by an increased emphasis on independence across the home-care agency
      involved, together with other methodological problems encountered, is thought to
      account for the few differences between groups in individual outcomes. Despite no
      difference between the groups over time in their overall ADL scores, a
      significantly smaller proportion of the HIP group required assistance with
      bathing/showering, the most common reason for referral, at 3 and 12 months. The
      results support earlier findings that participating in a short-term restorative
      programme appears to reduce the need for ongoing home care. The implementation of
      such programmes more broadly throughout Australia could substantially offset the
      projected increase in demand for home care associated with the five-fold
      projected increase in numbers of the oldest old expected over the next 40 years.

PMID- 23009673
TI  - Laserspray ionization imaging of multiply charged ions using a commercial vacuum
      MALDI ion source.
AB  - This is the first report of imaging mass spectrometry (MS) from multiply charged
      ions at vacuum. Laserspray ionization (LSI) was recently extended to applications
      at vacuum producing electrospray ionization-like multiply charged ions directly
      from surfaces using a commercial intermediate pressure matrix-assisted laser
      desorption/ionization ion mobility spectrometry (IMS) MS instrument. Here, we
      developed a strategy to image multiply charged peptide ions. This is achieved by
      the use of 2-nitrophloroglucinol as matrix for spray deposition onto the tissue
      section and implementation of "soft" acquisition conditions including lower laser
      power and ion accelerating voltages similar to electrospray ionization-like
      conditions. Sufficient ion abundance is generated by the vacuum LSI method to
      employ IMS separation in imaging multiply charged ions obtained on a commercial
      mass spectrometer ion source without physical instrument modifications using the
      laser in the commercially available reflection geometry alignment. IMS gas-phase
      separation reduces the complexity of the ion signal from the tissue, especially
      for multiply charged relative to abundant singly charged ions from tissue lipids.
      We show examples of LSI tissue imaging from charge state +2 of three endogenous
      peptides consisting of between 1 and 16 amino acid residues from the acetylated N
      terminal end of myelin basic protein: mass-to-charge (m/z) 795.81 (+2) molecular
      weight (MW) 1589.6, m/z 831.35 (+2) MW 1660.7, and m/z 917.40 (+2) MW 1832.8.

PMID- 23009674
TI  - The evolution of breast self-examination to breast awareness.

PMID- 23009676
TI  - The ESX/type VII secretion system modulates development, but not virulence, of
      the plant pathogen Streptomyces scabies.
AB  - Streptomyces scabies is a model organism for the investigation of plant-microbe
      interactions in Gram-positive bacteria. Here, we investigate the type VII protein
      secretion system (T7SS) in S. scabies; the T7SS is required for the virulence of
      other Gram-positive bacteria, including Mycobacterium tuberculosis and
      Staphylococcus aureus. The hallmarks of a functional T7SS are an EccC protein
      that forms an essential component of the secretion apparatus and two small,
      sequence-related substrate proteins, EsxA and EsxB. A putative transmembrane
      protein, EccD, may also be associated with T7S in Actinobacteria. In this study,
      we constructed strains of the plant pathogen S. scabies carrying marked mutations
      in genes coding for EccC, EccD, EsxA and EsxB. Unexpectedly, we showed that all
      four mutant strains retain full virulence towards several plant hosts. However,
      disruption of the esxA or esxB, but not eccC or eccD, genes affects S. scabies
      development, including a delay in sporulation, abnormal spore chains and
      resistance to lysis by the Streptomyces-specific phage phiC31. We further showed
      that these phenotypes are specific to the loss of the T7SS substrate proteins
      EsxA and EsxB, and are not observed when components of the T7SS secretion
      machinery are lacking. Taken together, these results imply an unexpected
      intracellular role for EsxA and EsxB.

PMID- 23009675
TI  - De novo mutations in neurological and psychiatric disorders: effects, diagnosis
      and prevention.
AB  - Neurological and psychiatric disorders account for a considerable proportion of
      the global disease burden. Although there is a high heritability and a
      significant genetic component in these disorders, the genetic cause of most cases
      has yet to be identified. Advances in DNA sequencing allowing the analysis of the
      whole human genome in a single experiment have led to an acceleration of the
      discovery of the genetic factors associated with human disease. Recent studies
      using these platforms have highlighted the important role of de novo mutations in
      neurological and psychiatric disorders. These findings have opened new avenues
      into the understanding of genetic disease mechanisms. These discoveries, combined
      with the increasing ease with which we can sequence the human genome, have
      important implications for diagnosis, prevention and treatment. Here, we present
      an overview of the recent discovery of de novo mutations using key examples of
      neurological and psychiatric disorders. We also discuss the impact of
      technological developments on diagnosis and prevention. 

PMID- 23009677
TI  - Unemployment, gender and mental health: the role of the gender regime.
AB  - Existing research suggests that gender differences in the effect of unemployment
      on mental health are related to the different positions and roles that are
      available for men and women in society and the family; roles that are connected
      with their different psychosocial and economic need for employment. The aim of
      this article is to analyse the role of gender in the relationship between
      unemployment and mental wellbeing in Sweden, representing a gender regime with a
      similar need for employment among women and men, and Ireland, representing a
      gender regime in which the need for employment differs between women and men. The
      results, based on longitudinal data from the two countries, show that
      unemployment was more negatively related to mental health among men than among
      women in Ireland, while men and women were equally affected by unemployment in
      Sweden. Factors related to the family and economic situation, as well as gendered
      selection into the unemployment population, explains the difference in mental
      health between unemployed men and women in Ireland. The overall conclusion is
      that the context has a major influence on the relationship between unemployment,
      gender and mental health. 

PMID- 23009678
TI  - Anaesthesia monitor alarms: a theory-driven approach.
AB  - The development of physiologic monitors has contributed to the decline in
      morbidity and mortality in patients undergoing anaesthesia. Diverse factors
      (physiologic, technical, historical and medico-legal) create challenges for
      monitor alarm designers. Indeed, a growing body of literature suggests that
      alarms function sub-optimally in supporting the human operator. Despite existing
      technology that could allow more appropriate design, most anaesthesia alarms
      still operate on simple, pre-set thresholds. Arguing that more alarms do not
      necessarily make for safer alarms is difficult in a litigious medico-legal
      environment and a competitive marketplace. The resultant commitment to the status
      quo exposes the risks that a lack of an evidence-based theoretical framework for
      anaesthesia alarm design presents. In this review, two specific theoretical
      foundations with relevance to anaesthesia alarms are summarised. The potential
      significance that signal detection theory and cognitive systems engineering could
      have in improving anaesthesia alarm design is outlined and future research
      directions are suggested. PRACTITIONER SUMMARY: The development of physiologic
      monitors has increased safety for patients undergoing anaesthesia. Evidence
      suggests that the full potential of the alarms embedded within those monitors is
      not being realised. In this review article, the authors propose a theoretical
      framework that could lead to the development of more ergonomic anaesthesia
      alarms.

PMID- 23009679
TI  - [1.1]Ferrocenophanes and bis(ferrocenyl) species with aluminum and gallium as
      bridging elements: synthesis, characterization, and electrochemical studies.
AB  - Salt-metathesis reactions between dilithioferrocene (Li(2)fc.2/3tmeda) and
      intramolecularly coordinated aluminum and gallium species RECl(2) [R = 5-Me(3)Si
      2-(Me(2)NCH(2))C(6)H(3); E = Al (2a), Ga (2b); and R = (2-C(5)H(4)N)Me(2)SiCH(2);
      E = Al (3a), Ga (3b)] gave respective [1.1]ferrocenophanes ([1.1]FCPs). Those
      obtained from 2a and 2b, respectively, were isolated as analytically pure
      compounds and fully characterized including single-crystal X-ray structure
      determinations [4a (Al): 43%; 4b (Ga): 47%]. Bis(ferrocenyl) compounds of the
      type REFc(2) [R = 5-Me(3)Si-2-(Me(2)NCH(2))C(6)H(3); E = Al (5a), Ga (5b); and R
      = (2-C(5)H(4)N)Me(2)SiCH(2); E = Al (6a), Ga (6b)] and R(2)SiFc(2) [R = Me
      (7(Me)); Et (7(Et))] were prepared, starting from respective element dichlorides
      and lithioferrocene (LiFc). Molecular structures of 6a, 7(Me), and 7(Et) were
      solved by single-crystal X-ray analyses. One of the two Fc moieties of 6a was
      bent toward the open coordination site of the aluminum atom. The measured dip
      angles alpha* of the two independent molecules in the asymmetric unit were
      11.9(5) and 13.3(5) degrees , respectively. The redox behavior of [1.1]FCPs 4 and
      bis(ferrocenyl) species 5, 6, 7, and (Mamx)EFc(2) [Mamx = 2,4-tBu(2)-6
      (Me(2)NCH(2))C(6)H(2); E = Al (8a), Ga (8b)] were investigated with cyclic
      voltammetry. While all gallium and silicon compounds gave meaningful and
      interpretable data, all aluminum compounds were problematic with the exception of
      8a. Aluminum species, compared to respective gallium species, are more sensitive
      and, presumably, fluoride ions or residual water from the electrolyte and solvent
      are causing degradation. The splitting between the formal potentials for
      bis(ferrocenyl) species was significantly smaller (5b, 6b, and 8b: DeltaE degrees
      ' = 0.138-0.159 V) than that of the [1.1]FCP 4b (DeltaE degrees ' = 0.309 V).
      These results were explained by assuming an electrostatic interaction between the
      two iron centers; differences between bis(ferrocenyl) species and [1.1]FCPs are
      likely due to a more effective solvation of Fe-containing moieties in the more
      flexible bis(ferrocenyl) species.

PMID- 23009680
TI  - Academic achievement after extreme prematurity: optimizing outcomes for
      vulnerable children in times of uncertainty.

PMID- 23009681
TI  - Myeloperoxidase catalyzes the conjugation of serotonin to thiols via free
      radicals and tryptamine-4,5-dione.
AB  - Serotonin (5-hydroxytryptamine; 5HT) is a favorable substrate for myeloperoxidase
      and is likely to be oxidized by this heme enzyme during inflammation. In this
      study, we have investigated how serotonin becomes conjugated to amino acid
      residues and proteins when it is oxidized by myeloperoxidase. 5HT formed three
      adducts with N-acetylcysteine (NAC) when it was incubated with myeloperoxidase,
      xanthine oxidase, and acetaldehyde. One of the adducts was identified as 5HT-NAC,
      and the others were conjugates of NAC and tryptamine-4,5-dione (TD). There was no
      evidence for coupling of oxidized serotonin to amine residues. Glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) was exposed to 5HT with the enzymatic system or
      synthetic TD. Both caused a loss of thiols on GAPDH and covalent attachment of
      quinones derived from TD to the protein. Biotin-labeled 5HT was used instead of
      5HT to confirm the conjugation of 5HT to GAPDH. It was incorporated into the
      GAPDH when oxidized by myeloperoxidase. Analysis of tryptic peptides of human
      GAPDH by liquid chromatography with mass spectrometry revealed that an adduct of
      TD was formed with the peptide containing Cys(152) and Cys(156). Our results
      indicate that myeloperoxidase can oxidize serotonin to species that form adducts
      with low molecular weight thiols and cysteine residues in proteins. Low molecular
      weight conjugates will redox cycle and fuel oxidative stress. Conjugation of
      serotonin to proteins will affect their function and may provide useful
      biomarkers of serotonin oxidation during inflammatory events.

PMID- 23009682
TI  - Electrochemical switching of photoelectrochemical processes at CdS QDs and
      photosystem I-modified electrodes.
AB  - Photoactive inorganic CdS quantum dots (QDs) or the native photosystem I (PSI) is
      immobilized onto a pyrroloquinoline quinone (PQQ) monolayer linked to Au
      electrodes to yield hybrid relay/QDs (or photosystem) assemblies. By the
      electrochemical biasing of the electrode potential, the relay units are retained
      in their oxidized PQQ or reduced PQQH(2) states. The oxidized or reduced states
      of the relay units dictate the direction of the photocurrent (anodic or
      cathodic). By the cyclic biasing of the electrode potential between the values E
      >= -0.05 V and E <= -0.3 V vs Ag quasi-reference electrode (Ag QRE), retaining
      the relay units in the oxidized PQQ or reduced PQQH(2) states, the photocurrents
      are respectively switched between anodic and cathodic values. Different
      configurations of electrically switchable photoelectrochemical systems are
      described: (i) the PQQ/CdS QDs/(triethanolamine, TEOA) or PQQ/PSI/(ascorbic
      acid/dichlorophenolindophenol, DCPIP) systems, leading to anodic photocurrents;
      (ii) the PQQ/CdS QDs (or PSI)/(flavin adenine dinucleotide) systems, leading to
      cathodic photocurrents; (iii) the PQQ/CdS QDs (or PSI)/(O(2)) switchable systems,
      leading to cyclic anodic/cathodic switching of the photocurrents.

PMID- 23009683
TI  - Monocenter feasibility study of the MRI compatibility of the Evia pacemaker in
      combination with Safio S pacemaker lead.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of the
      magnetic resonance (MR) conditional pacemaker (PM) system (Evia SR-T and DR-T
      with Safio S leads) under MR conditions. METHODS: Patients with standard PM
      indications and Evia PM were eligible for enrollment in this single center
      prospective non-randomized pilot study. Patients underwent MR of the brain and
      lower lumbar spine at 1.5 Tesla. Atrial (RA) und ventricular (RV) lead parameters
      (sensing, pacing threshold [PTH], pacing impedance) were assessed immediately
      before (baseline follow-up [FU]) and immediately after MRI (1st FU), after 1
      month (2nd FU) and 3 months (3rd FU). The effect of MR on serious adverse device
      effect (SADE) free-rate, on atrial and ventricular sensing (AS/VS; mV) and atrial
      (RA) and ventricular (RV) pacing thresholds (PTH; V/0.4 ms) were investigated
      between baseline and 2nd FU. Continuous variables are expressed as mean +/- SD
      and were compared using paired Student's t-test. A p < 0.05 was considered
      significant. RESULTS: Thirty-one patients were enrolled. One patient had to be
      excluded because of an enrollment violation. Therefore, data of 30 patients
      (female 12 [40%], age 73 +/- 12 years, dual chamber PM 15 [50%]) were included in
      this analysis. No MR related SADE occurred. Lead measurements were not
      statistically different between the baseline FU and the 2nd FU (AS/VS at baseline
      3.2 +/- 2.1/15.0 +/- 6.0, at 2nd FU 3.2 +/- 2.1/14.9 +/- 6.5; p = ns. RA-PTH/RV
      PTH at baseline 0.68 +/- 0.18/0.78 +/- 0.22, at 2nd FU 0.71 +/- 0.24/0.78 +/-
      0.22; p = ns). The presence of the permanent pacemakers led to MR imaging
      artifacts on diffusion weighted sequences of the brain, but did not affect other
      sequences (e.g. FLAIR and T2 weighted spin-echo images). CONCLUSION: The use of
      the MR conditional Evia PM in a MR environment under predefined conditions is
      feasible. No MR related SADEs nor clinically relevant changes in device functions
      occurred.

PMID- 23009684
TI  - Genetic structure of community acquired methicillin-resistant Staphylococcus
      aureus USA300.
AB  - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) is a significant bacterial pathogen that poses considerable clinical and
      public health challenges. The majority of the CA-MRSA disease burden consists of
      skin and soft tissue infections (SSTI) not associated with significant morbidity;
      however, CA-MRSA also causes severe, invasive infections resulting in significant
      morbidity and mortality. The broad range of disease severity may be influenced by
      bacterial genetic variation. RESULTS: We sequenced the complete genomes of 36 CA
      MRSA clinical isolates from the predominant North American community acquired
      clonal type USA300 (18 SSTI and 18 severe infection-associated isolates). While
      all 36 isolates shared remarkable genetic similarity, we found greater overall
      time-dependent sequence diversity among SSTI isolates. In addition, pathway
      analysis of non-synonymous variations revealed increased sequence diversity in
      the putative virulence genes of SSTI isolates. CONCLUSIONS: Here we report the
      first whole genome survey of diverse clinical isolates of the USA300 lineage and
      describe the evolution of the pathogen over time within a defined geographic
      area. The results demonstrate the close relatedness of clinically independent CA
      MRSA isolates, which carry implications for understanding CA-MRSA epidemiology
      and combating its spread.

PMID- 23009685
TI  - Engineered measles virus Edmonston strain used as a novel oncolytic viral system
      against human hepatoblastoma.
AB  - BACKGROUND: Hepatoblastoma (HB) is the most common primary, malignant pediatric
      liver tumor in children. The treatment results for affected children have
      markedly improved in recent decades. However, the prognosis for high-risk
      patients who have extrahepatic extensions, invasion of the large hepatic veins,
      distant metastases and very high alpha-fetoprotein (AFP) serum levels remains
      poor. There is an urgent need for the development of novel therapeutic
      approaches. METHODS: An attenuated strain of measles virus, derived from the
      Edmonston vaccine lineage, was genetically engineered to produce carcinoembryonic
      antigen (CEA). We investigated the antitumor potential of this novel viral agent
      against human HB both in vitro and in vivo. RESULTS: Infection of the Hep2G and
      HUH6 HB cell lines, at multiplicities of infection (MOIs) ranging from 0.01 to 1,
      resulted in a significant cytopathic effect consisting of extensive syncytia
      formation and massive cell death at 72-96 h after infection. Both of the HB lines
      overexpressed the measles virus receptor CD46 and supported robust viral
      replication, which correlated with CEA production. The efficacy of this approach
      in vivo was examined in murine Hep2G xenograft models. Flow cytometry assays
      indicated an apoptotic mechanism of cell death. Intratumoral administration of MV
      CEA resulted in statistically significant delay of tumor growth and prolongation
      of survival. CONCLUSIONS: The engineered measles virus Edmonston strain MV-CEA
      has potent therapeutic efficacy against HB cell lines and xenografts. Trackable
      measles virus derivatives merit further exploration in HB treatment.

PMID- 23009686
TI  - Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression
      in Malaysian women.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of
      breast cancer characterized by the lack of estrogen receptor (ER), progesterone
      receptor (PR) and the human epidermal growth factor receptor 2 (HER2)
      expressions. This subgroup of refractory disease tends to have aggressive
      clinical behavior, high frequency of metastasis and lack of response to current
      hormonal or targeted therapies. Despite numerous studies reporting the
      clinicopathological features of TNBC and its association with the basal-like
      phenotype in the Western population, only limited data are available in the Asian
      population. Therefore, the aim of this study was to investigate the
      clinicopathological characteristics of TNBC and its association with epidermal
      growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6) and mast/stem cell growth
      factor receptor (c-KIT or CD117) expression in Malaysian women. METHODS: A total
      of 340 patients diagnosed with primary breast cancer between 2002 and 2006 in
      Malaysia were reviewed and analyzed. RESULTS: The incidence of TNBC was 12.4%
      (42/340). Bivariate analysis revealed that TNBC was strongly associated with a
      younger age, higher grade tumor and p53 expression. Further immunohistochemical
      analysis suggested that TNBC in Malaysian women was strongly associated with
      EGFR, CK5/6 and c-KIT expression with high a Ki-67 proliferation index.
      CONCLUSION: In conclusion, our study confirms the association of TNBC with basal
      like marker expression (EGFR, CK5/6 and c-KIT) in Malaysian women, consistent
      with studies in other populations.

PMID- 23009687
TI  - The effect of infection order of porcine circovirus type 2 and porcine
      reproductive and respiratory syndrome virus on dually infected swine alveolar
      macrophages.
AB  - BACKGROUND: Concurrent infection with porcine circovirus type 2 (PCV2) and
      porcine reproductive and respiratory syndrome virus (PRRSV) is known as one of
      the major causes for porcine respiratory disease complex (PRDC). Dual infection
      with PCV2 and PRRSV is consistently to have more severe clinical presentations
      and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it
      is not known if dual infections with PCV2 and PRRSV in different infection order
      may lead to different clinical symptoms in the host. To mimic the possible field
      conditions, swine alveolar macrophages (AMs) were inoculated with PCV2 and PRRSV
      in vitro simultaneously or with one virus 18 h earlier than the other. The cell
      viability, cytopathic effects, antigen-containing rates, phagocytotic and
      microbial killing capabilities, cytokine profiles (IL-8, TNF-alpha, and IFN
      alpha) and FasL transcripts were determined, analyzed, and compared to prove the
      hypothesis. RESULTS: A marked reduction in PRRSV antigen-containing rate,
      cytopathic effect, and TNF-alpha expression level was revealed in AMs inoculated
      with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then
      PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h
      later. Transient decrease in phagocytosis but constant reduction in microbicidal
      capability in AMs in the group inoculated with PCV2 alone and constant decrease
      in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups
      were noted. The levels of IL-8, TNF-alpha, IFN-alpha, and FasL transcripts in AMs
      in all groups with dual inoculation of PCV2 and PRRSV were significantly
      increased regardless of the infection orders as compared with infection by PCV2
      alone or PRRSV alone. CONCLUSIONS: Swine AMs infected with PCV2 first then PRRSV
      later or infected with PCV2 and PRRSV simultaneously displayed marked reduction
      in PRRSV antigen-containing rate, cytopathic effect, and TNF-alpha expression
      level. The different inoculation orders of PCV2 and PRRSV in AMs leading to
      different results in viral antigen positivity, cytopathology, and cytokine
      profile may explain, at least partially, the underlying mechanism of the enhanced
      pulmonary lesions in PRDC exerted by dual infection with PCV2 and PRRSV and the
      variable clinical manifestations of PRDC-affected pigs in the field.

PMID- 23009688
TI  - Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy,
      safety and exploratory analysis of role of serum thyroglobulin and FDG-PET.
AB  - CONTEXT: Radioactive iodine is a crucial tool for treatment of differentiated
      thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an
      aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We
      report the experience of off-label use of the tyrosine kinase inhibitor sorafenib
      for treatment of advanced iodine-refractory DTC. DESIGN: Patients with
      progressive DTC refractory to radioactive iodine were treated with sorafenib used
      off-label independently from their performance status. Primary study end-points
      were radiological response, progression-free survival (PFS) and safety. Secondary
      end-points were site-specific radiological response and overall survival (OS). An
      exploratory analysis of the role of serum thyroglobulin (Tg) and
      fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed.
      RESULTS: A total of 17 patients were included in the study. Median follow-up was
      15.5 months. Clinical benefit was obtained in 71% of subjects (30% partial
      response and 41% stable disease). Sorafenib was mostly well tolerated, but a high
      incidence of fatal events was reported (three patients died from severe bleeding
      events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10
      months. The best responses were observed in lymph nodes and lung. Baseline Tg
      levels and the Tg response to treatment were correlated to both radiological
      response and PFS. Baseline FDG-PET assessment and early FDG-PET response were
      correlated to radiological response. CONCLUSIONS: Sorafenib allows morphological
      disease control in the majority of patients with iodine-refractory DTC.
      Progression-free survival and overall survival were lower than in previous
      studies as a consequence of the worse clinical condition of our patients.
      Sorafenib is mostly well tolerated but could have been responsible for the
      reported fatal events. Baseline Tg and the Tg response to treatment could be
      useful for predicting morphological response and clinical outcome. Early FDG-PET
      response could be helpful for the timely identification of nonresponding
      patients.

PMID- 23009689
TI  - Plane of best fit: a novel method to characterize the three-dimensionality of
      molecules.
AB  - We describe a computational method, plane of best fit (PBF), to quantify and
      characterize the 3D character of molecules. This method is rapid and amenable to
      analysis of large diverse data sets. We compare PBF with alternative literature
      methods used to assess 3D character and apply the method to diverse data sets of
      fragment-like, drug-like, and natural product compound libraries. We show that
      exemplar fragment libraries underexploit the potential of 3D character in
      fragment-like chemical space and that drug-like molecules in the libraries
      examined are predominantly 2D in character.

PMID- 23009690
TI  - Foliage response of young central European oaks to air warming, drought and soil
      type.
AB  - Three Central European oak species, with four provenances each, were
      experimentally tested in 16 large model ecosystem chambers for their response to
      passive air warming (AW, ambient +1-2  degrees C), drought (D, -43 to -60%
      irrigation) and their combination (AWD) for 3 years on two forest soil types of
      pH 4 or 7. Throughout the entire experiment, the influence of the different
      ambient and experimental climates on the oak trees was strong. The morphological
      traits of the Quercus species were affected in opposing ways in AW and D
      treatments, with a neutral effect in the AWD treatment. Biochemical parameters
      and LMA showed low relative plasticity compared to the morphological and growth
      parameters. The high plasticity in physiologically important parameters of the
      three species, such as number of intercalary veins or leaf size, indicated good
      drought acclimation properties. The soil type influenced leaf chlorophyll
      concentration, C/N and area more than drought, whereas foliage mass was more
      dependent on drought than on soil type. Through comparison of visible symptom
      development with the water deficits, a drought tolerance threshold of -1.3 MPa
      was determined. Although Q. pubescens had xeromorphic leaf characteristics (small
      leaf size, lower leaf water content, high LMA, pilosity, more chlorophyll, higher
      C/N) and less response to the treatments than Q. petraea and Q. robur, it
      suffered more leaf drought injury and shedding of leaves than Q. petraea.
      However, if foliage mass were used as the criterion for sustainable performance
      under a future climate, Q. robur would be the most appropriate species.

PMID- 23009691
TI  - Structural attributes for the recognition of weak and anomalous regions in coiled
      coils of myosins and other motor proteins.
AB  - BACKGROUND: Coiled-coils are found in different proteins like transcription
      factors, myosin tail domain, tropomyosin, leucine zippers and kinesins. Analysis
      of various structures containing coiled-coils has revealed the importance of
      electrostatic and hydrophobic interactions. In such domains, regions of different
      strength of interactions need to be identified since they could be biologically
      relevant. FINDINGS: We have updated our coiled-coil validation webserver, now
      called COILCHECK+, where new features were added to efficiently identify the
      strength of interaction at the interface region and measure the density of
      charged residues and hydrophobic residues. We have examined charged residues and
      hydrophobic ladders, using a new algorithm called CHAHO, which is incorporated
      within COILCHECK + server. CHAHO permits the identification of spatial charged
      residue patches and the continuity of hydrophobic ladder which stabilizes and
      destabilizes the coiled-coil structure. CONCLUSIONS: The availability of such
      computational tools should be useful to understand the importance of spatial
      clustering of charged residues and the continuity of hydrophobic residues at the
      interface region of coiled-coil dimers. COILCHECK + is a structure based tool to
      validate coiled-coil stability; it can be accessed at
      http://caps.ncbs.res.in/coilcheckplus.

PMID- 23009692
TI  - Heterobimetallic MOFs containing tetrathiocyanometallate building blocks:
      pressure-induced spin crossover in the porous {Fe(II)(pz)[Pd(II)(SCN)4]} 3D
      coordination polymer.
AB  - Here we describe the synthesis, structure, and magnetic properties of two related
      coordination polymers made up of self-assembling Fe(II) ions, pyrazine (pz), and
      the tetrathiocyanopalladate anion. Compound {Fe(MeOH)(2)[Pd(SCN)(4)]}.pz (1a) is
      a two-dimensional coordination polymer where the Fe(II) ions are equatorially
      coordinated by the nitrogen atoms of four [Pd(SCN)(4)](2-) anions, each of which
      connects four Fe(II) ions, forming corrugated layers {Fe[Pd(SCN)(4)]}(infinity).
      The coordination sphere of Fe(II) is completed by the oxygen atoms of two CH(3)OH
      molecules. The layers stack one on top of each other in such a way that the
      included pz molecule establishes strong hydrogen bonds with the coordinated
      methanol molecules of adjacent layers. Compound {Fe(pz)[Pd(SCN)(4)]} (2) is a
      three-dimensional porous coordination polymer formed by flat
      {Fe[Pd(SCN)(4)]}(infinity) layers pillared by the pz ligand. Thermal analysis of
      1a shows a clear desorption of the two coordinated CH(3)OH molecules giving a
      rather stable phase (1b), which presumably is a polymorphic form of 2. The
      magnetic properties of the three derivatives are typical of the high-spin Fe(II)
      compounds. However, compounds 1b and 2, with coordination sphere [FeN(6)], show
      thermal spin crossover behavior at pressures higher than ambient pressure (10(5)
      MPa).

PMID- 23009694
TI  - Micro-micro hierarchy replacing micro-nano hierarchy: a precisely controlled way
      to produce wear-resistant superhydrophobic polymer surfaces.
AB  - Superhydrophobic polymer surfaces are typically fabricated by combining
      hierarchical micro-nanostructures. The surfaces have a great technological
      potential because of their special water-repellent and self-cleaning properties.
      However, the poor mechanical robustness of such surfaces has severely limited
      their use in practical applications. This study presents a simple and swift mass
      production method for manufacturing hierarchically structured polymer surfaces at
      micrometer scale. Polypropylene surface structuring was done using injection
      molding, where the microstructured molds were made with a microworking robot. The
      effect of the micro-microstructuring on the polymer surface wettability and
      mechanical robustness was studied and compared to the corresponding properties of
      micro-nanostructured surfaces. The static contact angles of the micro
      microstructured surfaces were greater than 150 degrees  and the contact angle
      hysteresis was low, showing that the effect of hierarchy on the surface wetting
      properties works equally well at micrometer scale. Hierarchically micro
      microstructured polymer surfaces exhibited the same superhydrophobic wetting
      properties as did the hierarchically micro-nanostructured surfaces. Micro
      microstructures had superior mechanical robustness in wear tests as compared to
      the micro-nanostructured surfaces. The new microstructuring technique offers a
      precisely controlled way to produce superhydrophobic wetting properties to
      injection moldable polymers with sufficiently high intrinsic hydrophobicity.

PMID- 23009693
TI  - The reciprocal relationship between alliance and symptom improvement across the
      treatment of childhood anxiety.
AB  - This study examined changes in the therapeutic alliance and in self-reported
      anxiety over the course of 16 weeks of manual-based family treatment for child
      anxiety disorders. Eighty-six children (51.3% female; aged 7.15-14.44; 86.2%
      Caucasian, 14.8% minority) with a principal diagnosis of separation anxiety
      disorder, generalized anxiety disorder, and/or social phobia, and their parents,
      received family treatment for anxiety disorders in youth. Child, therapist, and
      parent ratings of therapeutic alliance and child ratings of state anxiety were
      measured each session. Latent difference score growth modeling investigated the
      interacting relationship. Therapeutic alliance change, as rated by the mother and
      by the therapist, was a significant predictor (medium effect) of latter change in
      child anxiety (with greater therapeutic alliance leading to later reduction in
      anxiety). However, changes in child-reported anxiety also predicted latter change
      in father- and therapist-reported alliance (small-to-medium effect). Prospective
      relationships between child-reported therapeutic alliance and child-reported
      symptom improvement were not significant. Results provide partial support for a
      reciprocal model in which therapeutic alliance improves outcome, and anxiety
      reduction improves therapeutic alliance.

PMID- 23009695
TI  - Feature selection and recognition from nonspecific volatile profiles for
      discrimination of apple juices according to variety and geographical origin.
AB  - Apple juice is a complex mixture of volatile and nonvolatile components. To
      develop discrimination models on the basis of the volatile composition for an
      efficient classification of apple juices according to apple variety and
      geographical origin, chromatography volatile profiles of 50 apple juice samples
      belonging to 6 varieties and from 5 counties of Shaanxi (China) were obtained by
      headspace solid-phase microextraction coupled with gas chromatography. The
      volatile profiles were processed as continuous and nonspecific signals through
      multivariate analysis techniques. Different preprocessing methods were applied to
      raw chromatographic data. The blind chemometric analysis of the preprocessed
      chromatographic profiles was carried out. Stepwise linear discriminant analysis
      (SLDA) revealed satisfactory discriminations of apple juices according to variety
      and geographical origin, provided respectively 100% and 89.8% success rate in
      terms of prediction ability. Finally, the discriminant volatile compounds
      selected by SLDA were identified by gas chromatography-mass spectrometry. The
      proposed strategy was able to verify the variety and geographical origin of apple
      juices involving only a reduced number of discriminate retention times selected
      by the stepwise procedure. This result encourages the similar procedures to be
      considered in quality control of apple juices. PRACTICAL APPLICATION: This work
      presented a method for an efficient discrimination of apple juices according to
      apple variety and geographical origin using HS-SPME-GC-MS together with
      chemometric tools. Discrimination models developed could help to achieve greater
      control over the quality of the juice and to detect possible adulteration of the
      product.

PMID- 23009697
TI  - New jobs old roles - working for prevention in a whole-system model of health and
      social care for older people.
AB  - The Partnerships for Older People Projects programme provided government funding
      for local and health authorities to pilot prevention and intervention services in
      partnership with the voluntary sector and older people between 2006 and 2009.
      This local evaluation of a pilot in southern England undertaken between 2007 and
      2009 used a Theory of Change approach to gathering and reflecting on data with
      different groups involved in the delivery of this whole-system based model of
      prevention. The model was delivered in the same way in seven social services
      locality areas within a large county authority. The method of data gathering
      enabled structured reflection on the implementation, development and projected
      outcomes of the model and a consideration of the key learning of working in a
      whole-system way with partners and stakeholders. The whole-system model, although
      complex and challenging to implement, was considered overall to have been a
      success and provided significant learning for partners and stakeholders on the
      challenges and benefits of working across professional and sectoral boundaries.
      New posts were created as part of the model. Two of these, recruited to and
      managed by voluntary sector partners, were identified as 'new jobs', but echoed
      'old roles' within community and voluntary sector based health and social care.
      The authors reflect on the parallels of these roles with previously existing
      roles and ways of working and reflect on how the whole-system approach of this
      particular pilot enabled these new jobs to develop in particularly appropriate
      and successful ways.

PMID- 23009698
TI  - A novel externally applied neuromuscular stimulator for the treatment of stress
      urinary incontinence in women--??a pilot study.
AB  - OBJECTIVES: ?? Neuromuscular electrical stimulation (NMES) is commonly used to
      treat lower urinary tract dysfunctions. This study evaluated the efficacy of a
      novel externally applied stimulator in the treatment of stress urinary
      incontinence (SUI). MATERIALS AND METHODS: ?? Nine women were included in this
      study. Provocative tests included a cough and jumping jack test assessed via pad
      weight. Ultrasound (US) imaging assessed pelvic floor muscle (PFM) contraction. A
      bladder filling protocol allowed for delineation of the bladder from the pelvic
      floor and standardized volume. External electrodes were used during 30 ??min, at
      least four times per week treatment protocol at home for eight weeks.
      Participants were blinded to US and were not instructed regarding pelvic floor
      contractions. RESULTS: ?? At week 1, participants could perform PFM contractions
      verified with US. More importantly, an 87.43% decrease in leakage was noted. At
      week 8, participants reported a 97.71% decrease in leakage (p= 0.0001). Changes
      noted in Incontinence Impact Questionnaire and Modified Oxford scores were
      significant (p= 0.0001 and p= 0.0001). CONCLUSIONS: ?? NMES is frequently used to
      promote muscle strength and coordination. Studies have shown NMES to be effective
      in decreasing symptoms associated with SUI; however, few, if any, have used it as
      a primary treatment modality. The novel device in this study was shown to be
      effective in improving muscle strength, reducing or ablating the symptoms
      associated with SUI, and in eliciting PFM contractions. The device is noninvasive
      and can be used as a home treatment.

PMID- 23009699
TI  - Methanotrophy in a Paleoproterozoic oil field ecosystem, Zaonega Formation,
      Karelia, Russia.
AB  - Organic carbon rich rocks in the c. 2.0 Ga Zaonega Formation (ZF), Karelia,
      Russia, preserve isotopic characteristics of a Paleoproterozoic ecosystem and
      record some of the oldest known oil generation and migration. Isotopic data
      derived from drill core material from the ZF show a shift in delta(13) C(org)
      from c. -250/00 in the lower part of the succession to c. -400/00 in the upper
      part. This stratigraphic shift is a primary feature and cannot be explained by
      oil migration, maturation effects, or metamorphic overprints. The shift toward
      (13) C-depleted organic matter (delta(13) C(org) < -250/00) broadly coincides
      with lithological evidence for the generation of oil and gas in the underlying
      sediments and seepage onto the sea floor. We propose that the availability of
      thermogenic CH(4) triggered the activity of methanotrophic organisms, resulting
      in the production of anomalously (13) C-depleted biomass. The stratigraphic shift
      in delta(13) C(org) records the change from CO(2) -fixing autotrophic biomass to
      biomass containing a significant contribution from methanotrophy. It has been
      suggested recently that this shift in delta(13) C(org) reflects global forcing
      and progressive oxidation of the Earth. However, the lithologic indication for
      local thermogenic CH(4) , sourced within the oil field, is consistent with
      basinal methanotrophy. This indicates that regional/basinal processes can also
      explain the delta(13) C(org) negative isotopic shift observed in the ZF.

PMID- 23009700
TI  - Rate of prescription of antidepressant and anxiolytic drugs after Cyclone Yasi in
      North Queensland.
AB  - INTRODUCTION: The need to manage psychological symptoms after disasters can
      result in an increase in the prescription of psychotropic drugs, including
      antidepressants and anxiolytics. Therefore, an increase in the prescription of
      antidepressants and anxiolytics could be an indicator of general psychological
      distress in the community. PURPOSE: The purpose of this study was to determine if
      there was a change in the rate of prescription of antidepressant and anxiolytic
      drugs following Cyclone Yasi. METHODS: A quantitative evaluation of new
      prescriptions of antidepressants and anxiolytics was conducted. The total number
      of new prescriptions for these drugs was calculated for the period six months
      after the cyclone and compared with the same six month period in the preceding
      year. Two control drugs were also included to rule out changes in the general
      rate of drug prescription in the affected communities. RESULTS: After Cyclone
      Yasi, there was an increase in the prescription of antidepressant drugs across
      all age and gender groups in the affected communities except for males 14-54
      years of age. The prescription of anxiolytic drugs decreased immediately after
      the cyclone, but increased by the end of the six-month post-cyclone period.
      Control drug prescription did not change. CONCLUSION: There was a quantifiable
      increase in the prescription of antidepressant drugs following Cyclone Yasi that
      may indicate an increase in psychosocial distress in the community.

PMID- 23009701
TI  - Machine learning applied to chemical analysis: sensing multiple biomarkers in
      simulated breath using a temperature-pulsed electronic-nose.
AB  - Monitoring of chemical species in breath offers an approach for the detection of
      disease and other conditions that cause homeostatic imbalance. Here, we
      demonstrate the use of microsensor-based devices for detecting select biomarkers
      in simulated exhaled breath as a step toward enabling fast and inexpensive breath
      screening technology. Microhotplate elements functionalized with three
      chemiresistive metal-oxide films (SnO(2), In(2)O(3), and CuO) were used to
      acquire data in simulated breath containing single targets [(5 to 20) MUmol/mol
      ammonia, methanol, and acetone], as well as mixtures of those species. All
      devices were operated with programmed thermal cycles featuring rapid temperature
      excursions, during which film resistances were measured. Material-specific
      temperature programs were optimized to achieve temperature-dependent metal-oxide
      sensing film conductance levels and target selectivity. A supervised hierarchical
      machine-learning algorithm using linear discriminant analysis for dimensional
      reduction of sensing data and discrimination was developed. This algorithm was
      employed in the classification and quantification of biomarkers. This approach to
      microsensor data collection and processing was successful in classifying and
      quantifying the model biomarkers in validation-set mixtures.

PMID- 23009702
TI  - Causes of death in infants admitted to Australian neonatal intensive care units
      between 1995 and 2006.
AB  - AIM: To compare causes and rates of mortality among infants admitted to 10
      Australian neonatal intensive care units (NICUs) between 1995 and 2006. METHODS:
      De-identified perinatal data from the Neonatal Intensive Care Units' (NICUS) Data
      Collection for 24 131 infants were examined for causes and rates of death. The
      study period was divided into two epochs: I (1995-2000, n = 11 185 infants) and
      II (2001-2006, n = 12 946 infants). RESULTS: A total of 2224 (9.2%) infants died
      in hospital. Mortality decreased from 10.3% (1152/11 185) in epoch I to 8.3%
      (1072/12 946) in epoch II (p < 0.001) due to improved survival in term infants.
      Extreme prematurity also decreased as a primary cause of death (118 (10.2%) vs 76
      (7.1%), p = 0.008). No infant >42-week gestation was admitted in epoch II.
      Congenital abnormalities were the most common cause of death (>20%) in both
      epochs, mostly in term rather than preterm infants (40.7% vs 13.9%, p < 0.001).
      Age of death was unchanged between the two epochs (median 4, 1st, 3rd quartiles:
      1,16 days). CONCLUSION: Mortality rates have continued to decrease but
      improvement is predominantly due to improved survival of term infants and
      prevention of postdate deliveries. Congenital abnormalities continue to be the
      most common cause of death.

PMID- 23009703
TI  - Phenylmethylsulfonyl fluoride, a potentiator of neuropathy, alters the
      interaction of organophosphorus compounds with soluble brain esterases.
AB  - Phenylmethylsulfonyl fluoride (PMSF) is a protease and esterase inhibitor that
      causes protection or potentiation/promotion of organophosphorus delayed
      neuropathy (OPIDN) depending on whether it is dosed before or after an inducer of
      delayed neuropathy. The molecular target of promotion has not yet been
      identified. Kinetic data of esterase inhibition were first obtained for PMSF with
      a soluble chicken brain fraction and then analyzed using a kinetic model with a
      multienzymatic system in which inhibition occurred with the simultaneous chemical
      hydrolysis of the inhibitor and ongoing inhibition (inhibition during the
      substrate reaction). The best fitting model was a model with resistant fraction,
      Ealpha (28%), and two sensitive enzymatic entities, Ebeta (61%) and Egamma (11%),
      with I(50) at 20 min of 70 and 447 MUM, respectively. The estimated constant of
      the chemical hydrolysis of PMSF was kh = 0.23 min(-1). Ealpha, which is sensitive
      to mipafox and resistant to PMSF, became less sensitive to mipafox when the
      preparation was preincubated with PMSF. Its Ealpha I(50) (30 min) of mipafox
      increased with the PMSF concentration used to preincubate it. Egamma is sensitive
      to both PMSF and mipafox, and after preincubation with PMSF, Egamma became less
      sensitive to mipafox and was totally resistant after preincubation with 10 MUM
      PMSF or more. The sensitivity of Ealpha to paraoxon (I(50) 30 min from 9 to 11
      nM) diminished after PMSF preincubation (I(50) 30 min 185 nM) and showed no
      spontaneous reactivation capacity. The nature of these interactions is unknown
      but might be due to covalent binding at sites other than the substrate catalytic
      center. Such interactions should be considered to interpret the
      potentiation/promotion phenomenon of PMSF and to understand the effects of
      multiple exposures to chemicals.

PMID- 23009704
TI  - Social network influences on smoking, drinking and drug use in secondary school:
      centrifugal and centripetal forces.
AB  - We explore how school experiences and social networks structure young people's
      substance use in different institutional contexts. The concepts of 'selection'
      and 'influence' are situated within the context of bounded agency, counter-school
      cultures and Bourdieusian notions of capital. We employed individual and group
      interviews, network-mapping, and observations at two contrasting English
      secondary schools. Both schools were characterised by extended social network
      structures that appeared to influence patterns of substance use, although the
      mechanisms via which this occurred varied according to school context. At Grange
      House school (suburban context) a minority of students from disadvantaged
      families were alienated by the attainment-focused regime, marginalised by a
      strong peer-led centrifugal force pushing them outwards, and substance use was an
      alternative source of bonding and identity for these students. In contrast, at
      North Street a centripetal force operated whereby the majority of students were
      pulled towards highly-visible, normative markers of 'safe', 'road culture', such
      as cannabis use and gang-involvement, as they attempted to fit in and survive in
      an inner-city school environment. We conclude that health inequalities may be
      reproduced through these distinctive centrifugal and centripetal forces in
      different institutional contexts, and this should be the focus of quantitative
      examination in the UK and elsewhere. 

PMID- 23009706
TI  - 15th International Congress on Behcet's Disease.

PMID- 23009705
TI  - Transcriptomic analysis of peritoneal cells in a mouse model of sepsis:
      confirmatory and novel results in early and late sepsis.
AB  - BACKGROUND: The events leading to sepsis start with an invasive infection of a
      primary organ of the body followed by an overwhelming systemic response. Intra
      abdominal infections are the second most common cause of sepsis. Peritoneal fluid
      is the primary site of infection in these cases. A microarray-based approach was
      used to study the temporal changes in cells from the peritoneal cavity of septic
      mice and to identify potential biomarkers and therapeutic targets for this subset
      of sepsis patients. RESULTS: We conducted microarray analysis of the peritoneal
      cells of mice infected with a non-pathogenic strain of Escherichia coli.
      Differentially expressed genes were identified at two early (1 h, 2 h) and one
      late time point (18 h). A multiplexed bead array analysis was used to confirm
      protein expression for several cytokines which showed differential expression at
      different time points based on the microarray data. Gene Ontology based
      hypothesis testing identified a positive bias of differentially expressed genes
      associated with cellular development and cell death at 2 h and 18 h respectively.
      Most differentially expressed genes common to all 3 time points had an immune
      response related function, consistent with the observation that a few bacteria
      are still present at 18 h. CONCLUSIONS: Transcriptional regulators like PLAGL2,
      EBF1, TCF7, KLF10 and SBNO2, previously not described in sepsis, are
      differentially expressed at early and late time points. Expression pattern for
      key biomarkers in this study is similar to that reported in human sepsis,
      indicating the suitability of this model for future studies of sepsis, and the
      observed differences in gene expression suggest species differences or
      differences in the response of blood leukocytes and peritoneal leukocytes.

PMID- 23009707
TI  - Antibacterial therapeutics for the treatment of chytrid infection in amphibians:
      Columbus's egg?
AB  - BACKGROUND: The establishment of safe and effective protocols to treat
      chytridiomycosis in amphibians is urgently required. In this study, the
      usefulness of antibacterial agents to clear chytridiomycosis from infected
      amphibians was evaluated. RESULTS: Florfenicol, sulfamethoxazole, sulfadiazine
      and the combination of trimethoprim and sulfonamides were active in vitro against
      cultures of five Batrachochytrium dendrobatidis strains containing sporangia and
      zoospores, with minimum inhibitory concentrations (MIC) of 0.5-1.0 MUg/ml for
      florfenicol and 8.0 MUg/ml for the sulfonamides. Trimethoprim was not capable of
      inhibiting growth but, combined with sulfonamides, reduced the time to visible
      growth inhibition by the sulfonamides. Growth inhibition of B. dendrobatidis was
      not observed after exposure to clindamycin, doxycycline, enrofloxacin,
      paromomycin, polymyxin E and tylosin. Cultures of sporangia and zoospores of B.
      dendrobatidis strains JEL423 and IA042 were killed completely after 14 days of
      exposure to 100 MUg/ml florfenicol or 16 MUg/ml trimethoprim combined with 80
      MUg/ml sulfadiazine. These concentrations were, however, not capable of
      efficiently killing zoospores within 4 days after exposure as assessed using flow
      cytometry. Florfenicol concentrations remained stable in a bathing solution
      during a ten day period. Exposure of Discoglossus scovazzi tadpoles for ten days
      to 100 MUg/ml but not to 10 MUg florfenicol /ml water resulted in toxicity. In an
      in vivo trial, post metamorphic Alytes muletensis, experimentally inoculated with
      B. dendrobatidis, were treated topically with a solution containing 10 MUg/ml of
      florfenicol during 14 days. Although a significant reduction of the B.
      dendrobatidis load was obtained, none of the treated animals cleared the
      infection. CONCLUSIONS: We thus conclude that, despite marked anti B.
      dendrobatidis activity in vitro, the florfenicol treatment used is not capable of
      eliminating B. dendrobatidis infections from amphibians.

PMID- 23009708
TI  - Pleural fluid cell-free DNA integrity index to identify cytologically negative
      malignant pleural effusions including mesotheliomas.
AB  - BACKGROUND: The diagnosis of malignant pleural effusions (MPE) is often
      clinically challenging, especially if the cytology is negative for malignancy.
      DNA integrity index has been reported to be a marker of malignancy. The aim of
      this study was to evaluate the utility of pleural fluid DNA integrity index in
      the diagnosis of MPE. METHODS: We studied 75 pleural fluid and matched serum
      samples from consecutive subjects. Pleural fluid and serum ALU DNA repeats
      [115bp, 247bp and 247bp/115bp ratio (DNA integrity index)] were assessed by real
      time quantitative PCR. Pleural fluid and serum mesothelin levels were quantified
      using ELISA. RESULTS: Based on clinico-pathological evaluation, 52 subjects had
      MPE (including 16 mesotheliomas) and 23 had benign effusions. Pleural fluid DNA
      integrity index was higher in MPE compared with benign effusions (1.2 vs. 0.8;
      p<0.001). Cytology had a sensitivity of 55% in diagnosing MPE. If cytology and
      pleural fluid DNA integrity index were considered together, they exhibited 81%
      sensitivity and 87% specificity in distinguishing benign and malignant effusions.
      In cytology-negative pleural effusions (35 MPE and 28 benign effusions), elevated
      pleural fluid DNA integrity index had an 81% positive predictive value in
      detecting MPEs. In the detection of mesothelioma, at a specificity of 90%,
      pleural fluid DNA integrity index had similar sensitivity to pleural fluid and
      serum mesothelin (75% each respectively). CONCLUSION: Pleural fluid DNA integrity
      index is a promising diagnostic biomarker for identification of MPEs, including
      mesothelioma. This biomarker may be particularly useful in cases of MPE where
      pleural aspirate cytology is negative, and could guide the decision to undertake
      more invasive definitive testing. A prospective validation study is being
      undertaken to validate our findings and test the clinical utility of this
      biomarker for altering clinical practice.

PMID- 23009709
TI  - A lower value for quantitative ultrasound at radius is an additional indicator of
      metabolic syndrome and cardiovascular disease risk.
AB  - BACKGROUND: The relationships between quantitative ultrasound (QUS) values,
      metabolic syndrome (MetS) and cardiovascular disease (CVD) risk are unclear.
      Objective The objective was to determine the relationships between QUS and MetS
      as well as CVD risk. DESIGN: This was a cross-sectional study conducted in
      Shanghai, China. PATIENTS: One-thousand four hundred and thirty-nine Chinese
      women and men with or without MetS were studied. MEASUREMENTS: Speed of sound
      (SOS) at radius, phalanx and tibia and their relationships with MetS and
      Framingham's 10-year cardiovascular disease risk scores were investigated.
      RESULTS: Premenopausal women with MetS had significant lower SOS at radius than
      those without MetS after adjusting for age, BMI and fat mass percentage (P =
      0.02). The radius SOS was negatively associated with waist circumference (r = 
      0.109, P = 0.025), waist-to-hip ratio (r = -0.124, P = 0.01) and 2 h postprandial
      glucose level (r = -0.125, P = 0.012) in premenopausal women. Waist
      circumference, waist-to-hip ratio and 2 h postprandial glucose level increased
      with the decreasing tertiles of radius SOS after adjustment of age (P = 0.003,
      0.002 and 0.008, respectively). The CVD risk increased with decreasing tertiles
      of radius SOS in postmenopausal women even after the adjustment of age, years
      since menopause, MetS components, smoking and alcohol habits (P < 0.001), but not
      in premenopausal women and men. CONCLUSIONS: Lower radius SOS is associated with
      greater risks of MetS and CVD in premenopausal and postmenopausal women,
      respectively. The QUS value derived from non-weight-bearing site, such as radius,
      may represent an additional indicator of MetS and CVD risk in women.

PMID- 23009710
TI  - Copper@polypyrrole nanocables.
AB  - A simple hydrothermal redox reaction between microcrystalline CuOHCl and pyrrole
      leads to the isolation of striking nanostructures formed by polypyrrole-coated
      copper nanocables. These multicomponent cables that feature single-crystalline
      face-centered cubic Cu cores (ca. 300 nm wide and up to 200 MUm long) are
      smoothly coated by conducting polypyrrole, which in addition to its
      functionality, offers protection against oxidation of the metal core.

PMID- 23009711
TI  - Controllable core-shell-type resin for solid-phase peptide synthesis.
AB  - A simple, mild, and inexpensive biphasic functionalization approach is attempted
      for preparing an ideal core-shell-type resin. The core-shell-type architecture
      was constructed by coupling Fmoc-OSu to the amino groups on the shell layer of an
      aminomethyl polystyrene (AM PS) resin. The shell layer thickness of the resin
      could be easily controlled under mild conditions, which was characterized by
      confocal laser scanning microscopy (CLSM). The efficiency of core-shell-type
      resin for solid-phase peptide synthesis (SPPS) was demonstrated by the synthesis
      of various peptides and compared with commercially available noncore-shell-type
      resins such as AM PS and poly(ethylene glycol)-based resins. The core-shell-type
      resin provided effective performance during the synthesis of hydrophobic peptide
      sequences, a disulfide-bridged cyclic peptide, and a difficult PNA sequence.
      Furthermore, a highly aggregative peptide fragment, MoPrP 105-125, was
      synthesized more efficiently on the core-shell-type resin under microwave
      conditions than AM PS and ChemMatrix resins.

PMID- 23009712
TI  - Stable isotope analysis of archaeological oak charcoal from eastern Anatolia as a
      marker of mid-Holocene climate change.
AB  - Comparison between modern trees and archaeological charred wood is an under
      explored method to study climate change, which may help to infer past
      environmental changes. The stable carbon content of deciduous oak charcoals was
      analysed for five periods covering more than a 1000 years (3350-2000 BC) at the
      site of Arslantepe, Turkey, together with modern deciduous oak specimens from
      five rare arboreal patches still present in the area (17-64 km from the site). In
      studies of past climate change it is difficult to distinguish human-induced
      changes from independent variations, such as the impact of past populations on
      the landscape and their relationship with climate changes in the mid-Holocene.
      Archaeology can evaluate climate signals preserved in fossil plants in light of
      past human life. This paper will contribute to understanding environmental
      changes that can be attributed to climate variation and those linked to human
      activities. We compared (13) C/(12) C of modern and fossil oaks in order to
      correlate the (13) C-content to environmental features of Arslantepe, both today
      and between 3350 and 2000 BC. At present, this area is semi-arid. The results
      show important similarities to palaeoenvironmental records for the rest of the
      Near East. The climate trend can be divided in three main phases: instability
      phase from ca. 3200 to 2900 BC; a phase of relative stability (until 2350 BC);
      and a final increase in aridity. The comparison of Delta(13) C values between
      fossil and modern plants shows that present climate is more arid than that
      between the end of the fourth and the whole third millennium BC.

PMID- 23009713
TI  - Personal health records in the preclinical medical curriculum: modeling student
      responses in a simple educational environment utilizing Google Health.
AB  - BACKGROUND: Various problems concerning the introduction of personal health
      records in everyday healthcare practice are reported to be associated with
      physicians' unfamiliarity with systematic means of electronically collecting
      health information about their patients (e.g. electronic health records--EHRs).
      Such barriers may further prevent the role physicians have in their patient
      encounters and the influence they can have in accelerating and diffusing personal
      health records (PHRs) to the patient community. One way to address these problems
      is through medical education on PHRs in the context of EHR activities within the
      undergraduate medical curriculum and the medical informatics courses in specific.
      In this paper, the development of an educational PHR activity based on Google
      Health is reported. Moreover, student responses on PHR's use and utility are
      collected and presented. The collected responses are then modelled to relate the
      satisfaction level of students in such a setting to the estimation about their
      attitude towards PHRs in the future. METHODS: The study was conducted by
      designing an educational scenario about PHRs, which consisted of student
      instruction on Google Health as a model PHR and followed the guidelines of a
      protocol that was constructed for this purpose. This scenario was applied to a
      sample of 338 first-year undergraduate medical students. A questionnaire was
      distributed to each one of them in order to obtain Likert-like scale data on the
      sample's response with respect to the PHR that was used; the data were then
      further analysed descriptively and in terms of a regression analysis to model
      hypothesised correlations. RESULTS: Students displayed, in general, satisfaction
      about the core PHR functions they used and they were optimistic about using them
      in the future, as they evaluated quite high up the level of their utility. The
      aspect they valued most in the PHR was its main role as a record-keeping tool,
      while their main concern was related to the negative effect their own opinion
      might have on the use of PHRs by patients. Finally, the estimate of their future
      attitudes towards PHR integration was found positively dependent of the level of
      PHR satisfaction that they gained through their experience (rho=0.524, p<0.001).
      CONCLUSIONS: The results indicate that students support PHRs as medical record
      keeping helpers and perceive them as beneficial to healthcare. They also
      underline the importance of achieving good educational experiences in improving
      PHR perspectives inside such educational activities. Further research is
      obviously needed to establish the relative long-term effect of education to other
      methods of exposing future physicians to PHRs.

PMID- 23009714
TI  - A fatality following ingestion of the designer drug meta-chlorophenylpiperazine
      (mCPP) in an asthmatic--HPLC-MS/MS detection in biofluids and hair.
AB  - A 20-year-old man, a cocaine addict and regular ecstasy user, with a medical
      history of allergic asthma died after ingesting half a tablet earlier the same
      day. The white tablet, stamped with a "smiling sun" logo looked very much like an
      ecstasy tablet and was sold as such. He experienced a severe asthma attack just
      after ingesting the half tablet and it evolved over the next few hours into fatal
      cardiorespiratory arrest. Biological samples, taken after embalming, were
      analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC
      MS/MS). Analysis revealed meta-chlorophenylpiperazine (mCPP) in concentrations of
      45.8 mg in a similar tablet obtained later from the drug dealer, 5.1 ng/mL in the
      bile, 0.3 ng/g in the liver, 15.0 ng/mL in the urine, and its absence in a hair
      sample (<0.02 ng/mg), which indicated he was not a regular user (whereas strong
      concentrations of MDMA and cocaine were found in the hair). Interrogated by the
      police after his arrest, the dealer said that he had sold the victim and for the
      very first time two tablets with the same "smiling sun" logo. The tablet used for
      analysis was from the same brand as the one ingested by the victim. The autopsy
      excluded other causes of death, while the histological analyses showed a large
      number of polynuclear eosinophils in the bronchial walls, confirming the
      asthmatic pathology. None of the other organs examined (larynx, liver, heart,
      adrenal glands, and kidneys) showed any distinctive signs, and in particular no
      inflammatory infiltrate. The death was the result of an asthma attack in an
      asthmatic person, violently decompensated following ingestion of approximately 20
      mg of mCPP.

PMID- 23009715
TI  - Perinatal characteristics among early (10-14 years old) and late (15-19 years
      old) pregnant adolescents.
AB  - BACKGROUND: Pregnancy in adolescents is a worldwide health problem and has been
      mostly common in poor populations. It is not clear if socioeconomic or biological
      factors are the main determinants of perinatal adverse outcomes in pregnant
      adolescents. Adolescents under 15 years old may present a high growth rate which
      may contribute to impair fetal growth. Our aim is to compare perinatal
      characteristics among early (aged 10 to 14 years) and late (aged 15 to 19 years)
      pregnant adolescents. METHODS: A cross-sectional study was performed using data
      from Pernambuco State 2009, obtained from DATASUS/SISNAC, a Brazilian Government,
      open-access public health database. Maternal and neonatal outcomes were compared
      between early (aged 10-14 years) and late (aged 15-19 years) pregnant
      adolescents. Family income was compared between early and late pregnant
      adolescents using a sample of 412 subjects evaluated at Instituto de Medicina
      Integral Prof. Fernando Figueira (IMIP) during 2011. Statistical comparisons were
      made using the chi-square test was used with a significant level of 0.05;
      bivariate and multivariate analysis were performed. This project was approved by
      the Institutional Ethics Review Board. RESULTS: Data from 31,209 pregnant
      adolescents were analyzed. 29,733 (95.2%) were aged 15 to 19 years and 1,476
      (4.7%) were aged 10 to 14 years. There were significant differences with respect
      to marital status, education level and number of prenatal visits of mothers aged
      10 to 14 years compared to 15 to 19 years. Of importance, early adolescents had a
      greater rate of neonates born premature and with low birth weight. Prematurity
      and low birth weight remained statistically significant after multivariate
      analysis. CONCLUSIONS: Early aged adolescents may have an increased risk of
      prematurity and low birth weight. These findings highlight the potential role of
      biological factors in newborn outcomes in pregnant adolescents.

PMID- 23009716
TI  - Correlating protein hot spot surface analysis using ProBiS with simulated free
      energies of protein-protein interfacial residues.
AB  - A protocol was developed for the computational determination of the contribution
      of interfacial amino acid residues to the free energy of protein-protein binding.
      Thermodynamic integration, based on molecular dynamics simulation in CHARMM, was
      used to determine the free energy associated with single point mutations to
      glycine in a protein-protein interface. The hot spot amino acids found in this
      way were then correlated to structural similarity scores detected by the ProBiS
      algorithm for local structural alignment. We find that amino acids with high
      structural similarity scores contribute on average -3.19 kcal/mol to the free
      energy of protein-protein binding and are thus correlated with hot spot residues,
      while residues with low similarity scores contribute on average only -0.43
      kcal/mol. This suggests that the local structural alignment method provides a
      good approximation of the contribution of a residue to the free energy of binding
      and is particularly useful for detection of hot spots in proteins with known
      structures but undetermined protein-protein complexes.

PMID- 23009717
TI  - Thoracic epidural steroid injection for rib fracture pain.
AB  - Treatment for rib fracture pain can be broadly divided into pharmacologic
      approaches with oral and/or parenteral medication and interventional approaches
      utilizing neuraxial analgesia or peripheral nerve blocks to provide pain relief.
      Both approaches attempt to control nociceptive and neuropathic pain secondary to
      osseous injury and nerve insult, respectively. Success of treatment is ultimately
      measured by the ability of the selected modality to decrease pain, chest
      splinting, and to prevent sequelae of injury, such as pneumonia. Typically,
      opioids and NSAIDs are the drugs of first choice for acute pain because of ease
      of administration, immediate onset of action, and rapid titration to effect. In
      contrast, neuropathic pain medications have a slower onset of action and are more
      difficult to titrate to therapeutic effect. Interventional approaches include
      interpleural catheters, intercostal nerve blocks, paravertebral nerve blocks, and
      thoracic and lumbar epidural catheters. Each intervention has its own inherent
      advantages, disadvantages, and success rates. Rib fracture pain management
      practice is founded on the thoracic surgical and anesthesiology literature.
      Articles addressing rib fracture pain are relatively scarce in the pain medicine
      literature. As life expectancy increases, and as healthcare system modifications
      are implemented, pain medicine physicians may be consulted to treat increasing
      number of patients suffering rib fracture pain and may need to resort to novel
      therapeutic measures because of financial constraints imposed by those changes.
      Here we present the first published case series of thoracic epidural steroid
      injections used for management of rib fracture pain.

PMID- 23009719
TI  - Monitoring a toxicological outbreak using Internet search query data.
AB  - BACKGROUND: A novel group of drugs of abuse colloquially known as "bath salts"
      had a dramatic rise in exposures recently noted in Europe and the United States.
      Internet search query data have been shown to be correlated with office visits
      for influenza-like illnesses. The purpose of this study was to determine whether
      internet search query data could have been used as a surveillance method for this
      outbreak. METHODS: This was a retrospective database review of the National
      Poison Database System and internet search query data provided by Google Insights
      for Search (GIS) comparing exposures reported to "bath salts" with internet
      searches for "bath salts". RESULTS: 1072 cases of exposures to "bath salts" were
      reported to US poison centers from 7/1/10 to 2/28/11. GIS data for the search
      term "bath salts" had a correlation of 0.84 with exposures to bath salts reported
      to US poison centers over the study period. Poison center exposures and GIS data
      did not differ significantly in detecting a change from the baseline (p = 0.85).
      When comparing exposures by state to search volumes by state for "bath salts",
      the correlation was 0.79. Symptoms and treatments were typical of an exposure to
      a sympathomimetic drug. CONCLUSIONS: Internet search data correlated very well
      with exposures reported to US poison centers for a novel drug of abuse. In this
      particular outbreak, it is possible that using internet search data may have
      provided a means for public health officials to monitor the rise in usage on a
      national and regional basis.

PMID- 23009718
TI  - Why do patients with long-term conditions use unscheduled care? A qualitative
      literature review.
AB  - Unscheduled care (UC) refers to non-routine face-to-face care, such as accident
      and emergency care, out-of-hours care, or walk-in centres. Current health service
      policy aims to reduce its use. Unscheduled care is common in people with long
      term conditions such as diabetes, asthma, chronic obstructive pulmonary disease
      and coronary heart disease. By reviewing qualitative research literature, we
      aimed to understand the breadth of psychosocial and other influences on UC use in
      people with long-term conditions. Few qualitative papers specifically address UC
      in patients in these disease groups. Therefore, our literature search also
      included qualitative research that explored factors potentially relevant to UC
      use, including attitudes to healthcare use in general. By searching Medline,
      Embase, Psycinfo and Cinahl from inception to 2011, we identified 42 papers,
      published since 1984, describing relevant original research and took a meta
      ethnographic approach in reviewing them. The review was conducted between Spring
      2009 and April 2011, with a further search in December 2011. Most papers reported
      on asthma (n = 13) or on multiple or unspecified conditions (n = 12). The most
      common methods reported were interviews (n = 33) and focus groups (n = 13), and
      analyses were generally descriptive. Theoretical and ethical background was
      rarely explicit, but the implicit starting point was generally the 'problem' of
      UC, and health-care, use in general, decontextualised from the lives of the
      patients using it. Patients' use of UC emerged as understandable, rational
      responses to pressing clinical need in situations in which patients thought it
      the only option. This belief reflected the value that they had learned to attach
      to UC versus routine care through previous experiences. For socially or
      economically marginalised patients, UC offered access to clinical or social care
      that was otherwise unavailable to them.

PMID- 23009720
TI  - Alarin 6-25Cys antagonizes alarin-specific effects on food intake and luteinizing
      hormone secretion.
AB  - Previous data from our labs and from others have demonstrated that
      intracerebroventricular (ICV) injection of alarin has orexigenic activity and
      significantly increases plasma luteinizing hormone (LH) secretion in a
      gonadotropin-releasing hormone (GnRH) dependent manner. The purpose of the
      current experiments was to determine if the amino acids at the amino-terminal end
      of the alarin peptide are critical for alarin's effects on reproductive and
      feeding systems. First, we injected male mice ICV with full-length alarin (Ala1
      25) or peptide fragments missing residues at the amino-terminal end (Ala3-25 or
      Ala6-25 Cys). Neither peptide fragment alone, significantly increased food intake
      in male mice compared to controls. Second, ICV injection of Ala1-25, but not Ala3
      25, significantly (p < 0.01) increased GnRH-mediated LH secretion. Surprisingly,
      Ala6-25 Cys significantly (p < 0.05) inhibited plasma LH secretion and inhibited
      Ala1-25 actions. In conclusion, elimination of the first five amino acids of
      alarin not only abolishes the biological activity of alarin, but becomes an
      antagonist to alarin-specific effects. Furthermore, Ala6-25 Cys seems to act as a
      specific antagonist to putative alarin receptors and therefore may be an
      important tool in identifying alarin-specific receptors.

PMID- 23009721
TI  - Empiricism in managing Behcet's syndrome.

PMID- 23009722
TI  - Electronic health records critical in the aftermath of disasters.

PMID- 23009723
TI  - Ocular melanoma and mammary mucinous carcinoma in an African lion.
AB  - BACKGROUND: Reports of neoplasms in Panthera species are increasing, but they are
      still an uncommon cause of disease and death in captive wild felids. The presence
      of two or more primary tumor in large felids is rarely reported, and there are no
      documented cases of ocular melanoma and mammary mucinous carcinoma in African
      lions. CASE PRESENTATION: An ocular melanoma and a mammary mucinous carcinoma are
      described in an African lion (Panthera leo). The first tumour was histologically
      characterized by the presence of epithelioid and fusiform melanocytes, while the
      latter was composed of mucus-producing cells with an epithelial phenotype that
      contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases
      of both tumor were identified in various organs and indirect immunohistochemistry
      was used to characterize them. Peribiliary cysts were observed in the liver.
      CONCLUSIONS: This is the first description of these tumor in African lions.

PMID- 23009725
TI  - Challenging deprotection steps during the synthesis of tetra- and pentasaccharide
      fragments of the Le(a)Le(x) tumor-associated hexasaccharide antigen.
AB  - We report the convergent synthesis of two novel tetrasaccharide and two novel
      pentasaccharide fragments of the Le(a)Le(x) TACA: the tetrasaccharides contain
      neither the galactose at the Le(a) nonreducing end nor the fucose at the Le(x)
      reducing end; the pentasaccharides only lack the galactose residue at the Le(a)
      nonreducing end. Two of the analogues were prepared as hexyl glycosides to be
      used in NMR experiments and as soluble inhibitors in binding studies and two as 6
      aminohexyl glycosides to be conjugated to carrier proteins. Our strategy relied
      on stepwise extensions using excess monosaccharide glycosyl donors
      (trichloroacetimidates and thioglycosides) in sequential glycosylation reactions.
      The protecting groups were chosen to limit the number of deprotection steps
      required to obtain the final derivatives. While this strategy ensured that all
      glycosylation reactions proceeded in very good yields (70-84%), deprotection of
      the oligosaccharide intermediates was challenging. Global deprotection using
      Birch metal dissolving conditions did not remove the tert-butyldiphenylsilyl
      group, which indeed was incompatible with such reaction conditions. Attempts to
      remove the TBDPS with tetrabutylammonium fluoride was unsuccessful and led to a
      complex mixture of compounds that could not be separated. The desired hexyl and
      aminohexyl tetrasaccharides were finally obtained after four- and five-step
      deprotection sequences, respectively. Deprotection of the pentasaccharide
      intermediate to give the hexyl and aminohexyl analogues also led to unexpected
      results. Indeed, during Zemplen deacylation, a chloroacetamide chlorine atom was
      displaced by methoxide ions leading to the corresponding methoxyacetamide. Once
      the chloroacetamide was fully reduced to an acetamide the pentasaccharides were
      obtained in four and five steps, respectively.

PMID- 23009724
TI  - Longitudinal effects of parental bereavement on adolescent developmental
      competence.
AB  - The aim of this study is to assess the impact of sudden parental bereavement on
      subsequent attainment of developmental competencies. This longitudinal study
      reports on 126 youth bereaved by sudden parental death (suicide, accident, or
      natural death) and 116 demographically similar nonbereaved controls assessed at
      9, 21, 33, and 62 months after parental death, and at comparable times in
      controls. Half were female and 84.7% Caucasian. Youths and care-giving parents
      were assessed on psychiatric disorders, psychological characteristics, and
      contextual variables antecedent and subsequent to bereavement. At Month 62, at
      which time youth on average aged 18.4 years (SD = 3.1), participants were
      assessed on developmental competence using an adaptation of the Status
      Questionnaire, peer attachment using the Inventory of Parent and Peer Attachment,
      and educational aspirations using the Future Expectations Scale. The bereaved and
      nonbereaved groups were compared using univariate and multivariate statistics,
      including path analyses. On univariate analyses, bereaved youth had more
      difficulties at work, less well-elaborated plans for career development, lower
      peer attachment, and diminished educational aspirations. The effects of
      bereavement were most commonly mediated via its effects on offspring and
      caregiver functioning and family climate, even after adjusting for the impact of
      predeath characteristics. Outcomes were unrelated to age at the time of parental
      death, gender of the deceased parent, or cause of death. Children who lost a
      parent to sudden death evidenced lower competence in work, peer relations, career
      planning, and educational aspirations, primarily mediated by the impact of
      bereavement on child and parental functioning and on family climate.

PMID- 23009726
TI  - Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non
      small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based
      chemotherapy (CT) at disease progression: a multicenter phase II trial (SAKK
      19/05).
AB  - PURPOSE: This phase II trial aimed to evaluate feasibility and efficacy of a
      first-line combination of targeted therapies for advanced non-squamous NSCLC:
      bevacizumab (B) and erlotinib (E), followed by platinum-based CT at disease
      progression (PD). METHODS: 103 patients with advanced non-squamous NSCLC were
      treated with B (15 mg/kg day 1 of each 21-day cycle) and E (150 mg daily) until
      PD or unacceptable toxicity. Upon PD patients received 6 cycles of CT
      (cisplatin/carboplatin and gemcitabine). The primary endpoint was disease
      stabilization rate (DSR) after 12 weeks of BE treatment. RESULTS: 101 patients
      were evaluable. Under BE, DSR at week 12 was 54.5%. 73 patients had at least
      stable disease (SD), including 1 complete remission and 17 partial responses
      (PR). No unexpected toxicities were observed. Median time to progression (TTP)
      under BE was 4.1 months. 62 patients started CT; 35 received at least 4 cycles (6
      PR, 32 SD). At a median follow-up of 36 months, median overall survival (OS) was
      14.1 months. CONCLUSIONS: First-line BE treatment followed by a fixed CT regimen
      at PD is feasible with acceptable toxicity and activity. In a non-squamous NSCLC
      population unselected for EGFR status, we found OS rates similar to standard CT.

PMID- 23009727
TI  - Metabolic imaging metrics correlate with survival in early stage lung cancer
      treated with stereotactic ablative radiotherapy.
AB  - BACKGROUND AND PURPOSE: To test whether (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography-computed tomography (PET-CT) imaging metrics correlate with
      outcomes in patients with stage I non-small cell lung cancer (NSCLC) treated with
      stereotactic ablative radiotherapy (SABR). MATERIAL AND METHODS: Fifty-four
      patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR
      PET within 6 months. We analyzed maximum standardized uptake value (SUV(max)) and
      metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7,
      and 10). Endpoints included primary tumor control (PTC), progression-free
      survival (PFS), overall survival (OS) and cancer-specific survival (CSS). We
      performed Kaplan-Meier, competing risk, and Cox proportional hazards survival
      analyses. RESULTS: Patients received 25-60 Gy in 1 to 5 fractions. Median follow
      up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83,
      87 and 94%, respectively. Pre-treatment SUV(max) (p=0.014), MTV(7) (p=0.0077),
      and MTV(10) (p=0.0039) correlated significantly with OS. In the low-MTV(7)vs.
      high-MTV(7) sub-groups, 1-year estimated OS was 100 vs. 78% (p=0.0077) and CSS
      was 100 vs. 88% (p=0.082). CONCLUSIONS: In this hypothesis-generating study we
      identified multiple pre-treatment PET-CT metrics as potential predictors of OS
      and CSS in patients with NSCLC treated with SABR. These could aid risk
      stratification and treatment individualization if validated prospectively.

PMID- 23009728
TI  - Increased knowledge of Francisella genus diversity highlights the benefits of
      optimised DNA-based assays.
AB  - BACKGROUND: Recent advances in sequencing technologies offer promising tools for
      generating large numbers of genomes, larger typing databases and improved mapping
      of environmental bacterial diversity. However, DNA-based methods for the
      detection of Francisella were developed with limited knowledge about genetic
      diversity. This, together with the high sequence identity between several
      Francisella species, means there is a high risk of false identification and
      detection of the highly virulent pathogen Francisella tularensis. Moreover,
      phylogenetic reconstructions using single or limited numbers of marker sequences
      often result in incorrect tree topologies and inferred evolutionary distances.
      The recent growth in publicly accessible whole-genome sequences now allows
      evaluation of published genetic markers to determine optimal combinations of
      markers that minimise both time and laboratory costs. RESULTS: In the present
      study, we evaluated 38 previously published DNA markers and the corresponding PCR
      primers against 42 genomes representing the currently known diversity of the
      genus Francisella. The results highlight that PCR assays for Francisella
      tularensis are often complicated by low specificity, resulting in a high
      probability of false positives. A method to select a set of one to seven markers
      for obtaining optimal phylogenetic resolution or diagnostic accuracy is
      presented. CONCLUSIONS: Current multiple-locus sequence-typing systems and
      detection assays of Francisella, could be improved by redesigning some of the
      primers and reselecting typing markers. The use of only a few optimally selected
      sequence-typing markers allows construction of phylogenetic topologies with
      almost the same accuracy as topologies based on whole-genome sequences.

PMID- 23009729
TI  - Dysfunctional problem-based learning curricula: resolving the problem.
AB  - BACKGROUND: Problem-based learning (PBL) has become the most significant
      innovation in medical education of the past 40 years. In contrast to exam
      centered, lecture-based conventional curricula, PBL is a comprehensive curricular
      strategy that fosters student-centred learning and the skills desired in
      physicians. The rapid spread of PBL has produced many variants. One of the most
      common is 'hybrid PBL' where conventional teaching methods are implemented
      alongside PBL. This paper contends that the mixing of these two opposing
      educational philosophies can undermine PBL and nullify its positive benefits.
      Schools using hybrid PBL and lacking medical education expertise may end up with
      a dysfunctional curriculum worse off than the traditional approach. DISCUSSION:
      For hybrid PBL schools with a dysfunctional curriculum, standard PBL is a cost
      feasible option that confers the benefits of the PBL approach. This paper
      describes the signs of a dysfunctional PBL curriculum to aid hybrid PBL schools
      in recognising curricular breakdown. Next it discusses alternative curricular
      strategies and costs associated with PBL. It then details the four critical
      factors for successful conversion to standard PBL: dealing with staff resistance,
      understanding the role of lectures, adequate time for preparation and support
      from the administrative leadership. SUMMARY: Hybrid PBL curricula without
      oversight by staff with medical education expertise can degenerate into
      dysfunctional curricula inferior even to the traditional approach from which PBL
      emerged. Such schools should inspect their curriculum periodically for signs of
      dysfunction to enable timely corrective action. A decision to convert fully to
      standard PBL is cost feasible but will require time, expertise and commitment
      which is only sustainable with supportive leadership.

PMID- 23009730
TI  - Update on antimicrobial susceptibility trends among Streptococcus pneumoniae in
      the United States: report of ceftaroline activity from the SENTRY Antimicrobial
      Surveillance Program (1998-2011).
AB  - A 14-year longitudinal survey of Streptococcus pneumoniae (18,911) strains by the
      SENTRY Antimicrobial Surveillance Program shows significant increases in
      resistance to amoxicillin/clavulanate (18.9%), penicillin at a MIC of >= 4 MUg/mL
      (14.8%), and ceftriaxone (11.7%) among 2011 isolates. Fluoroquinolones
      (levofloxacin; 98.8% susceptible) and ceftaroline (99.1-100.0% susceptible
      depending on breakpoint criteria) exhibited high levels of potency, as did
      linezolid, tigecycline, and vancomycin (100.0%). In summary, resistance rates to
      several antimicrobials continue to rise after introductions of both pneumococcal
      conjugate vaccines, as noted from these results for 1998 through 2011.

PMID- 23009732
TI  - Inviting pain? Pain, dualism and embodiment in narratives of self-injury.
AB  - The role of pain in the practice of self-injury is not straightforward. Existing
      accounts suggest that self-injury does not cause 'physical' pain, however self
      injury is also said to alleviate 'emotional' pain by inflicting 'physical' pain.
      This article explores these tensions using sociological theories regarding the
      socio-cultural and subjective nature of pain. Analysis derives from in-depth,
      life-story interviews carried out in the UK with people who had self-injured.
      Findings contribute to on-going debates within social science regarding the
      nature of pain. Participants' narratives about pain and self-injury both drew on
      and challenged dualistic models of embodiment. I suggest that self-injury offers
      a unique case on which to extend existing theoretical work, which has tended to
      focus on pain as an unwanted and uninvited entity. In contrast, accounts of self
      injury can feature pain as a central aspect of the practice, voluntarily invited
      into lived experience. 

PMID- 23009731
TI  - Outcomes in patients tested for Clostridium difficile toxins.
AB  - Clostridium difficile testing is shifting from toxin detection to C. difficile
      detection. Yet, up to 60% of patients with C. difficile by culture test negative
      for toxins and it is unclear whether they are infected or carriers. We reviewed
      medical records for 7046 inpatients with a C. difficile toxin test from 2005 to
      2009 to determine the duration of diarrhea and rate of complications and
      mortality among toxin-positive (toxin+) and toxin- patients. Overall, toxin-
      patients had less severe diarrhea, fewer diarrhea days, and lower mortality (P <
      0.001, all comparisons) than toxin+ patients. One toxin- patient (n = 1/6121;
      0.02%) was diagnosed with pseudomembranous colitis, but there were no
      complications such as megacolon or colectomy for fulminant CDI among toxin-
      patients. These data suggest that C. difficile-attributable complications are
      rare among patients testing negative for C. difficile toxins. More studies are
      needed to evaluate the clinical significance of C. difficile detection in toxin-
      patients.

PMID- 23009733
TI  - Microplasma illumination enhancement of vertically aligned conducting
      ultrananocrystalline diamond nanorods.
AB  - Vertically aligned conducting ultrananocrystalline diamond (UNCD) nanorods are
      fabricated using the reactive ion etching method incorporated with nanodiamond
      particles as mask. High electrical conductivity of 275 Omega.cm-1 is obtained for
      UNCD nanorods. The microplasma cavities using UNCD nanorods as cathode show
      enhanced plasma illumination characteristics of low threshold field of 0.21 V/MUm
      with plasma current density of 7.06 mA/cm2 at an applied field of 0.35 V/MUm.
      Such superior electrical properties of UNCD nanorods with high aspect ratio
      potentially make a significant impact on the diamond-based microplasma display
      technology.

PMID- 23009734
TI  - Reproducibility of intraocular pressure peak and fluctuation of the water
      drinking test.
AB  - BACKGROUND: The water-drinking test has been used as a stress test to evaluate
      the drainage system of the eye. However, in order to be clinically applicable,a
      test must provide reproducible results with consistent measurements. This study
      was performed to verify the reproducibility of intraocular pressure peaks and
      fluctuation detected during the water-drinking test in patients with ocular
      hypertension and open-angle glaucoma. DESIGN: A prospective analysis of patients
      in a tertiary care unit for glaucoma treatment. PARTICIPANTS: Twenty-four ocular
      hypertension and 64 open-angle glaucoma patients not under treatment. METHODS:
      The water-drinking test was performed in 2 consecutive days by the same examiners
      in patients not under treatment. Reproducibility was assessed using the
      intraclass correlation coefficient. MAIN OUTCOME MEASURES: Peak and fluctuation
      of intraocular pressure obtained with the water-drinking test were analysed for
      reproducibility. RESULTS: Eighty-eight eyes from 24 ocular hypertension and 64
      open-angle glaucoma patients not under treatment were evaluated. Test and retest
      intraocular pressure peak values were 28.38 +/- 4.64 and 28.38 +/- 4.56 mmHg,
      respectively (P = 1.00). Test and retest intraocular pressure fluctuation values
      were 5.75 +/- 3.9 and 4.99 +/- 2.7 mmHg, respectively (P = 0.06). Based on
      intraclass coefficient, reproducibility was excellent for peak intraocular
      pressure (intraclass correlation coefficient = 0.79) and fair for intraocular
      pressure fluctuation (intraclass correlation coefficient = 0.37). CONCLUSION:
      Intraocular pressure peaks detected during the water-drinking test presented
      excellent reproducibility, whereas the reproducibility of fluctuation was
      considered fair.

PMID- 23009735
TI  - Sex estimation of infants between birth and one year through discriminant
      analysis of the humerus and femur.
AB  - Estimation of sex when investigating subadult skeletal remains is largely
      problematic because of unreliable and inaccurate results. Despite the limitations
      encountered with skeletal material, the medical literature clearly demonstrates
      differences between males and females in utero that persist through life. The
      current study investigates sexual dimorphism in the long bones of the humerus and
      femur for individuals between birth and 1 year of age. A radiographic sample
      amassed from Erie County Medical Examiner's office includes 85 femoral and 45
      humeral images for analysis in relation to sex. Measurements for lengths and
      breadths were collected through tpsDig software. Discriminant analysis proved to
      be the most successful method, with error rates of 3% when utilizing maximum
      breadth at midshaft of the femur and 11% with humerus maximum distal breadth.
      This research demonstrates that it is possible to correctly classify sex of
      unknown subadult remains when comparing them to a known sample.

PMID- 23009736
TI  - Tumor size as measured at initial X-ray examination, not length of bile duct
      stricture, predicts survival in patients with unresectable pancreatic cancer.
AB  - BACKGROUND: The survival of unresectable pancreatic cancer patients is extremely
      poor. The aim of this study was to examine if tumor size could predict survival
      length in order to optimize patient care. METHODS: A retrospective observational
      study was performed on 185 consecutive patients with unresectable pancreatic
      cancer (ICD10: C250-2 and C258) who were diagnosed from 2003 to May 2010. The
      patients' initial radiographs at presentation of symptoms were reviewed by the
      same radiologist, and tumor extent was determined. RESULTS: The largest tumor
      diameter of the primary tumor was measured in 132 patients, 22 by an ultrasound
      and the other patients by a CT scan. In 53 patients, the tumor size could not be
      delimited and measured. Seventy-five patients (41%) had liver metastases at
      presentation of symptoms. Median survival for the entire patient group was only
      119 days. The median diameter of the patient's largest tumor was 4.35 cm, while
      the sample groups ranged from 1.2 to 14 cm. Patients were divided into two
      groups: those with a largest tumor diameter of <= 4.3 cm (66 patients) and those
      with a largest tumor diameter of > 4.3 cm (66 patients). Median survival for
      these groups was 149 and 94 days (p = 0.019), respectively. Cox regression showed
      a hazard ratio for tumor size of 1.48 (95% CI 1.02, 2.07) (p = 0.038), adjusted
      for the gemcitabine treatment which had been given to 49 patients and the
      presence of liver metastasis. In 88 patients, stricture length could be measured
      at ERCP. When comparing stricture lengths of <= 2 cm and > 2 cm, no difference in
      survival time was noted within a Kaplan-Meier analysis. CONCLUSION: The size of
      the maximum tumor diameter of the primary tumor during the initial X-ray
      examination of patients with pancreatic cancer may predict survival time for
      those patients who had no surgical resection. Stricture length at ERCP gave no
      information on survival.

PMID- 23009737
TI  - Daily sugar-sweetened beverage consumption and insulin resistance in European
      adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence)
      Study.
AB  - OBJECTIVE: The present study aimed to evaluate the relationship between the
      consumption of selected food groups and insulin resistance, with an emphasis on
      sugar-sweetened beverages (SSB). DESIGN: The present research is a large
      multicentre European study in adolescents, the HELENA-CSS (Healthy Lifestyle in
      Europe by Nutrition in Adolescence Cross-Sectional Study). SETTING: Homeostasis
      model assessment-insulin resistance index (HOMA-IR) was calculated. Several
      anthropometric and lifestyle characteristics were recorded. Dietary assessment
      was conducted by using a short FFQ. SUBJECTS: The participants were a subset of
      the original sample (n 546) with complete data on glucose, insulin and FFQ. All
      participants were recruited at schools. RESULTS: Median (25th, 75th percentile)
      HOMA-IR was 0.62 (0.44, 0.87). Mean HOMA-IR was significantly higher among
      adolescents consuming brown bread <=1 time/week than among those consuming 2-6
      times/week (P = 0.011). Mean values of HOMA-IR were also higher in adolescents
      consuming SSB >5 times/week compared with those consuming less frequently,
      although a statistically significant difference was detected between those
      consuming SSB 5-6 times/week and 2-4 times/week (P = 0.049). Multiple linear
      regression analysis showed that only the frequency of SSB consumption was
      significantly associated with HOMA-IR after controlling for potential
      confounders. In particular, it was found that HOMA-IR levels were higher among
      adolescents consuming SSB 5-6 times/week and >=1 time/d compared with those
      consuming <=1 time/week by 0.281 and 0.191 units, respectively (P = 0.009 and
      0.046, respectively). CONCLUSIONS: The present study revealed that daily
      consumption of SSB was related with increased HOMA-IR in adolescents.

PMID- 23009738
TI  - Determinants of engagement in HIV treatment and care among Zambians new to
      antiretroviral therapy.
AB  - This pilot study assessed the determinants of engagement in HIV care among
      Zambian patients new to antiretroviral (ARV) therapy, and the effect of an
      intervention to increase medication adherence. Participants (n = 160) were
      randomized to a 3-month group or individual intervention utilizing a crossover
      design. Psychophysiological (depression, cognitive functioning, health status),
      social (social support, disclosure, stigma), structural factors (health care
      access, patient-provider communication), and treatment engagement (adherence to
      clinic visits and medication) were assessed. Participants initially receiving the
      group intervention improved their adherence, but gains were not maintained
      following crossover to the individual intervention. Increased social support and
      patient-provider communication and decreased concern about HIV medications
      predicted increased clinic attendance across both arms. Results suggest that
      early participation in a group intervention may promote increased adherence among
      patients new to ARV therapy, but long-term engagement in care may be sustained by
      both one-on-one and group interventions by health care staff.

PMID- 23009739
TI  - Yield and cost effectiveness of mycobacterial infection detection using a simple
      IGRA-based protocol in UK subjects with inflammatory bowel disease suitable for
      anti-TNFalpha therapy.
AB  - BACKGROUND AND AIMS: Testing for LTBI is recommended prior to anti-TNFalpha
      agents. This includes an assessment of TB risk factors, chest radiograph, and
      interferon-gamma release assay alone or with concurrent Tuberculin skin testing.
      Here we review our experience and cost-effectiveness of using T-SPOT.TB IGRA to
      detect mycobacterial infection in patients with IBD suitable for anti-TNFalpha
      therapy. METHODS: This was a single-centre, retrospective review and economic
      evaluation (compared to British Thoracic Society guidance) of 125 adult IBD
      patients (90 anti-TNFalpha naive, 35 established on anti-TNFalpha) tested for
      LTBI using T-SPOT.TB IGRA. RESULTS: All subjects had normal chest radiographs and
      no clinical evidence for TB. 109 (87%) were BCG vaccinated. 27 (22%) of all
      patients tested were not using immunomodulation at the time of testing. 66 (53%)
      were taking thiopurines, 22 (18%)corticosteroids, and 35 (28%) anti-TNFalpha
      agents. One hundred twenty two (98%) had a negative IGRA result, two (2%) had
      positive results, and one (1%) had an indeterminate IGRA. A strategy using IGRA
      to guide TB preventative treatment produced cost savings of L10.79 per person
      compared to the BTS guidance. Eighty eight percent of the anti-TNFalpha naive
      group have subsequently received treatment with either infliximab or adalimumab
      (median follow-up of 24 months, IQR 18-30) with no cases of TB disease occurring.
      CONCLUSIONS: The use of a simple screening protocol for LTBI incorporating T
      SPOT.TB IGRA in place of TST in a largely BCG vaccinated population, many using
      immunomodulatory agents, appears to work well and is a cost-effective strategy in
      our IBD service.

PMID- 23009740
TI  - Behcet's syndrome: a critical digest of the recent literature.
AB  - A similar disease severity among men and women in Brasil, a high frequency of
      gastrointestinal involvement in China, Japan and USA, a low frequency of pathergy
      positivity in Japan and USA underline the ethnic variations reported in recent
      studies. Polymorphisms pertaining both to innate and adaptive immunity in genome
      wide association studies, clusters in phenotype, and new mechanisms for emerging
      therapeutic implications have been reported. A Th17 dominance seems to be likely
      with the exception of gastrointestinal involvement. Infliximab, interferon-alpha
      and cyclosporine-A may be showing their beneficial effects also by affecting the
      Th17 cells. The clinical course and outcome of isolated pulmonary artery
      thrombosis is similar to pulmonary artery aneurysms. Parenchymal lesions
      (nodules, consolidations, cavities and ground glass lesions) are common in
      patients with pulmonary involvement. Pericarditis is a frequent cardiac
      manifestation in France. Treatment of BS became more intensive than before.
      Immunosuppressives and corticosteroids seem to prevent relapses of venous
      thrombosis. Studies are needed to understand the role of anticoagulants.
      Interferon alpha-2a appears to be effective at lower dosage, which brings the
      advantage of decreased cost and increased tolerability. Switching between anti
      TNF agents, when needed, is possible. Interleukin-1 and interleukin-6 are new
      promising targets.

PMID- 23009742
TI  - Access and acceptability of community-based services for older Greek migrants in
      Australia: user and provider perspectives.
AB  - In most developed nations, ageing migrants represent a growing proportion of the
      older population. Policies that emphasise care in the community depend on older
      migrants having access to formal services along with informal support, yet little
      is known about how older migrants experience community-based formal services. By
      examining the views of both Greek elders in Australia and those of formal service
      providers, this research fills an important gap in the literature around access
      to and acceptability of formal community-based services for older migrants. A
      research team including two Greek background researchers used existing social
      groups and a snowball sampling method to conduct face-to-face interviews and
      focus groups with seventy older Greeks in Adelaide, Australia. In addition, 22
      community-based service providers were interviewed over the telephone. Results
      from users and providers showed that while many older Greeks experience service
      access issues, they also relied heavily on family for support and assistance at
      home. Reliance on family was both in preference to formal services or where
      formal services were used, to locate, negotiate and monitor such services. Common
      barriers identified by both groups included cost, transport and availability, but
      additional challenges were posed by language, literacy and cultural attitudes.
      Demographic changes including greater employment mobility and female workforce
      participation among adult children will have implications for both formal and
      informal care providers. Formal service providers need to ensure that services
      are promoted and delivered to take account of the important role of family in
      informal support while also addressing the access challenges posed by language
      and literacy. Research conducted by researchers from the same cultural background
      in the respondent's native language can further advance knowledge in this area.

PMID- 23009741
TI  - Ocular perfusion pressure and ocular blood flow in glaucoma.
AB  - Glaucoma is a progressive optic neuropathy of unknown origin. It has been
      hypothesized that a vascular component is involved in glaucoma pathophysiology.
      This hypothesis has gained support from studies showing that reduced ocular
      perfusion pressure is a risk factor for the disease. The exact nature of the
      involvement is, however, still a matter of debate. Based on recent evidence we
      propose a model including primary and secondary insults in glaucoma. The primary
      insult appears to happen at the optic nerve head. Increased intraocular pressure
      and ischemia at the post-laminar optic nerve head affects retinal ganglion cell
      axons. Modulating factors are the biomechanical properties of the tissues and
      cerebrospinal fluid pressure. After this primary insult retinal ganglion cells
      function at a reduced energy level and are sensitive to secondary insults. These
      secondary insults may happen if ocular perfusion pressure falls below the lower
      limit of autoregulation or if neurovascular coupling fails. Evidence for both
      faulty autoregulation and reduced hyperemic response to neuronal stimulation has
      been provided in glaucoma patients. The mechanisms appear to involve vascular
      endothelial dysfunction and impaired astrocyte-vessel signaling. A more detailed
      understanding of these pathways is required to direct neuroprotective strategies
      via the neurovascular pathway.

PMID- 23009743
TI  - Youth anxiety and parent factors over time: directionality of change among youth
      treated for anxiety.
AB  - The relationship between improvements in child anxiety and changes in parent
      factors (e.g., parental anxiety, parenting behaviors) is poorly understood. The
      present study investigated the directionality of change for child anxiety and
      parent factors among youth treated for anxiety disorders. Structural equation
      modeling examined these relationships pre- to posttreatment and at 1-year follow
      up for 111 youth aged 7 to 14 (57% male, 84% Caucasian). Child anxiety was
      measured using the Anxiety Disorders Interview Schedule for Children and the
      Child Behavior Checklist. The State-Trait Anxiety Inventory, Children's Report of
      Parental Behavior Inventory, and Family Assessment Device were used to measure
      maternal anxiety, psychological control, behavior control, and family affective
      involvement. Findings suggest that decreases in mother-reported child anxiety led
      to decreases in maternal anxiety. Decreases in maternal psychological control and
      family affective involvement preceded decreases in clinician-rated child anxiety.
      Youth who showed the most reductions in anxiety over the course of treatment were
      those who tended to have lower family affective involvement, behavior control,
      and maternal anxiety at pretreatment. Stability of the parent factors and child
      anxiety over time suggest that stability was greater for behavior control and
      maternal anxiety relative to affective involvement and psychological control. The
      findings are consistent with previous research indicating the importance of these
      parent factors as they relate to anxiety in youth. Furthermore, results indicate
      that changes in child anxiety may precede changes in parent factors and suggest
      that parental psychological control and affective involvement are important
      treatment targets for youth with anxiety disorders.

PMID- 23009745
TI  - Effects of corticosteroid, montelukast and iNOS inhibition on distal lung with
      chronic inflammation.
AB  - We evaluated the effects of anti-iNOS (1400W - W) associated with leukotriene
      antagonist (montelukast - M) or corticosteroid (dexamethasone - D) on distal lung
      of guinea pigs (GP) with chronic pulmonary inflammation. METHODS: GP were inhaled
      with ovalbumin (OVA-2*/week/4 weeks), treated with M (OVAM), D (OVAD) and/or W
      (OVAW, OVADW, OVAMW) and distal lungs were evaluated by morphometry. RESULTS:
      Isolated treatments were not sufficient to reduce all parameters. In OVADW, all
      parameters were reduced with greater reduction in elastic fibers, TIMP-1, IL-4,
      IL-5, IFN-gamma and PGF2-alpha compared with OVAD (p<0.05). OVAMW potentiated the
      reduction of actin, elastic fibers, TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma,
      iNOS, and PGF2-alpha to a greater extent than OVAM (p<0.05). A reduction of TIMP
      1, IL-4, IL-5, TGF-beta, IFN-gamma and iNOS was observed in OVADW compared with
      OVAMW (p<0.05). CONCLUSIONS: Although anti-iNOS paired with montelukast or
      dexamethasone yields better results than isolated treatments, the most effective
      pairing for controlling inflammation, oxidative stress and remodeling in this
      asthma model was found to be corticosteroids and anti-iNOS.

PMID- 23009746
TI  - RF performances of inductors integrated on localized p+-type porous silicon
      regions.
AB  - To study the influence of localized porous silicon regions on radiofrequency
      performances of passive devices, inductors were integrated on localized porous
      silicon regions, full porous silicon sheet, bulk silicon and glass substrates. In
      this work, a novel strong, resistant fluoropolymer mask is introduced to localize
      the porous silicon on the silicon wafer. Then, the quality factors and resonant
      frequencies obtained with the different substrates are presented. A first
      comparison is done between the performances of inductors integrated on same
      thickness localized and full porous silicon sheet layers. The effect of the
      silicon regions in the decrease of performances of localized porous silicon is
      discussed. Then, the study shows that the localized porous silicon substrate
      significantly reduces losses in comparison with high-resistivity silicon or
      highly doped silicon bulks. These results are promising for the integration of
      both passive and active devices on the same silicon/porous silicon hybrid
      substrate.

PMID- 23009744
TI  - A qualitative study using traditional community assemblies to investigate
      community perspectives on informed consent and research participation in western
      Kenya.
AB  - BACKGROUND: International collaborators face challenges in the design and
      implementation of ethical biomedical research. Evaluating community understanding
      of research and processes like informed consent may enable researchers to better
      protect research participants in a particular setting; however, there exist few
      studies examining community perspectives in health research, particularly in
      resource-limited settings, or strategies for engaging the community in research
      processes. Our goal was to inform ethical research practice in a biomedical
      research setting in western Kenya and similar resource-limited settings. METHODS:
      We sought to use mabaraza, traditional East African community assemblies, in a
      qualitative study to understand community perspectives on biomedical research and
      informed consent within a collaborative, multinational research network in
      western Kenya. Analyses included manual, progressive coding of transcripts from
      mabaraza to identify emerging central concepts. RESULTS: Our findings from two
      mabaraza with 108 community members revealed that, while participants understood
      some principles of biomedical research, they emphasized perceived benefits from
      participation in research over potential risks. Many community members equated
      health research with HIV testing or care, which may be explained in part by the
      setting of this particular study. In addition to valuing informed consent as
      understanding and accepting a role in research activities, participants endorsed
      an increased role for the community in making decisions about research
      participation, especially in the case of children, through a process of community
      consent. CONCLUSIONS: Our study suggests that international biomedical research
      must account for community understanding of research and informed consent,
      particularly when involving children. Moreover, traditional community forums,
      such as mabaraza in East Africa, can be used effectively to gather these data and
      may serve as a forum to further engage communities in community consent and other
      aspects of research.

PMID- 23009747
TI  - Experimental chronic ocular hypertension by anterior chamber injection of 0.3%
      carbomer solution in the rat.
AB  - BACKGROUND: To evaluate a chronic ocular hypertensive model by anterior chamber
      injection of 0.3% carbomer solution in rats. METHODS: Chronic ocular hypertension
      was induced unilaterally by injecting 20 MUL of 0.3% carbomer solution into the
      anterior chamber in 3-month-old Sprague Dawley rats. Intraocular pressure was
      measured everyday for 1 week and then every week for 2 months after a single or
      repeated injection. Retinal ganglion cell loss was assessed quantitatively using
      FluoroGold labelling at 2, 4 and 8 weeks after injection. Anterior chamber angle
      and optic nerve were examined after chronic intraocular pressure elevation.
      RESULTS: The mean and peak intraocular pressure of the injected eyes were
      elevated significantly higher than those of the control eyes for 6 weeks of the
      experiment, after a single injection of carbomer solution and a second injection
      at 2 weeks resulted in an 8-week elevation of the mean and peak intraocular
      pressure, which was significantly higher than those of the control eyes. Elevated
      intraocular pressure induced retinal ganglion cell loss by approximately 21%, 27%
      and 38% compared with that in the control eyes at 2, 4 and 8 weeks, respectively,
      after a single injection. In carbomer-injected eyes with chronic intraocular
      pressure elevation, the obstruction of anterior chamber angle by peripheral
      anterior synechia and optic nerve degeneration were observed. CONCLUSIONS:
      Anterior chamber injection of 0.3% carbomer solution was an effective and
      reproducible method to produce chronic intraocular pressure elevation and
      glaucomatous neurodegeneration in rats.

PMID- 23009749
TI  - The craft of intensive care medicine.
AB  - The practice of medicine is often represented as a dualism: is medicine a
      'science' or an 'art'? This dualism has been long-lasting, with evident appeal
      for the medical profession. It also appears to have been rhetorically powerful,
      for example in enabling clinicians to resist the encroachment of 'scientific'
      evidence-based medicine into core areas of medical work such as individual
      clinical judgement. In this article I want to make the case for a more valid
      conceptualisation of medical practice: that it is a 'craft' activity. The case I
      make is founded on a theoretical synthesis of the concept of craft, combined with
      an analysis of ethnographic observations of routine medical practice in intensive
      care. For this context the craft aspects of medical work can be seen in how
      biomedical and other types of knowledge are used in practice, the embodied skills
      and practical judgement of practitioners and the technological and material
      environment. These aspects are brought together in two conceptual dimensions for
      'craft': first, the application of knowledge; second, interaction with the
      material world. Some practical and political implications of a 'craft' metaphor
      for medical practice are noted. 

PMID- 23009748
TI  - Oxidative stress resistance genes contribute to the pathogenic potential of the
      anaerobic protozoan parasite, Entamoeba histolytica.
AB  - The protozoan parasite, Entamoeba histolytica, invades the host colon causing
      significant tissue destruction and inflammation. Upon host infection, the
      parasite is confronted with reactive oxygen and nitrogen species (ROS/RNS) that
      cause large-scale changes in gene expression profiles, which likely support the
      parasite's adaptation to the host environment. We have previously identified
      oxidative and nitrosative stress responsive genes using whole-genome expression
      profiling. Functional studies on two such genes are now reported and demonstrate
      that they have roles in parasite virulence. EHI_056680 encodes a small
      hypothetical protein named E. histolytica stress-induced adhesion factor
      (EhSIAF); EHI_188210 encodes a putative phospholipid transporting P-type
      ATPase/flippase (EhPTPA). Over-expression of each protein in E. histolytica
      trophozoites enhanced parasite survival in response to oxidative stress. Exposure
      to oxidative and nitrosative stress did not affect the localization of EhSIAF or
      EhPTPA but markedly increased EhPTPA protein levels. Interestingly, over
      expression of each gene resulted in parasites with increased adherence to healthy
      mammalian cells, but increased adherence to apoptotic cells was noted only in
      EhSIAF over-expressing parasites. However, despite having increased adherence to
      both healthy and apoptotic host cells, EhSIAF-over-expressing parasites were
      reduced in their ability to destroy mammalian cell monolayers, raising the
      intriguing possibility that EhSIAF over-expression caused signaling defects or
      resulted in a dominant negative phenotype. Over-expression of EhSIAF and EhPTPA
      also resulted in decreased motility in a transwell motility assay. Thus, we have
      confirmed that two genes that are upregulated by ROS confer increased resistance
      to oxidative stress and have identified an unexpected role of EhSIAF and EhPTPA
      in host cell adherence and a role of EhSIAF in parasite virulence. Our data imply
      that stress response genes may play multi-factorial roles in amoebic
      pathogenesis.

PMID- 23009750
TI  - Small molecule inhibitors of the hepatitis C virus-encoded NS5A protein.
AB  - Hepatitis C virus (HCV) is a modern-day pandemic; 2-3% of the world's population
      are thought to be infected with the virus and are subsequently at risk of
      developing end-stage liver diseases. The traditional standard of care (SOC) for
      HCV-infected patients has been limited to a regimen of pegylated-interferon alpha
      (pegIFN) and ribavirin; displaying low cure rates in a majority of patients and
      severe side effects. However, in 2011 the first direct-acting antivirals (DAA)
      were licensed to treat HCV-infected patients in combination with SOC, which
      served to elevate treatment response rates. The HCV drug development pipeline is
      currently populated with many additional and improved DAAs; primarily molecules
      that target the virus-encoded protease or polymerase enzymes. These molecules are
      being evaluated both in combination with the traditional SOC and together with
      other DAAs as all-oral pegIFN-free regimens with the ultimate goal of developing
      multiple DAA-containing HCV therapies that do not rely on an pegIFN backbone. A
      recent addition to the arsenal of HCV inhibitors in development is represented by
      an entirely new DAA class; molecules that target the HCV-encoded non-enzymatic
      NS5A protein. NS5A is essential for HCV propagation and, although its actual
      functions are largely unknown, it is likely a key regulator of viral genome
      replication and virion assembly. The protein is exquisitely sensitive to small
      molecule-mediated inhibition; NS5A-targeting molecules are probably the most
      potent antiviral molecules ever discovered and exhibit a number of other
      attractive drug-like properties, including activity against many HCV
      genotypes/subtypes and once-daily dosing potential. Although their mechanism of
      action is unclear, NS5A-targeting molecules are already proving their utility in
      clinical evaluation; particularly as components of pegIFN-sparring DAA
      combination regimens. This review will aim to amalgamate our current
      understanding and knowledge of NS5A-targeting molecules; their discovery,
      properties, applications, and insight into their future impact as components of
      all-oral pegIFN-free DAA combination therapies to combat HCV infection.

PMID- 23009751
TI  - Designing the eatwell week: the application of eatwell plate advice to weekly
      food intake.
AB  - OBJECTIVE: To develop a menu and resource to illustrate to consumers and health
      professionals what a healthy balanced diet looks like over the course of a week.
      DESIGN: Development and analysis of an illustrative 7 d 'eatwell week' menu to
      meet current UK recommendations for nutrients with a Dietary Reference Value,
      with a daily energy base of 8368 kJ (2000 kcal). Foods were selected using market
      research data on meals and snacks commonly consumed by UK adults. Analysis used
      the food composition data set from year 1 (2008) of the UK National Diet and
      Nutrition Survey rolling programme. The eatwell week menu was developed using an
      iterative process of nutritional analysis with adjustments made to portion sizes
      and the inclusion/exclusion of foods in order to achieve the target macronutrient
      composition. RESULTS: Three main meals and two snacks were presented as
      interchangeable within the weekdays and two weekend days to achieve adult food
      and nutrient recommendations. Main meals were based on potatoes, rice or pasta
      with fish (two meals; one oily), red meat (two meals), poultry or vegetarian
      accompaniments. The 5-a-day target for fruit and vegetables (range 5-6.7
      portions) was achieved daily. Mean salt content was below recommended maximum
      levels (<6 g/d). All key macro- and micronutrient values were achieved.
      CONCLUSIONS: Affordable foods, and those widely consumed by British adults, can
      be incorporated within a 7 d healthy balanced menu. Future research should
      investigate the effect of using the eatwell week on adults' dietary habits and
      health-related outcomes.

PMID- 23009752
TI  - FMF - clinical features, new treatments and the role of genetic modifiers: a
      critical digest of the 2010-2012 literature.
AB  - The last two years have been marked by many studies trying to better characterize
      the clinical features of FMF in children and proposal of new treatment for those
      who are resistant to colchicine. In addition, many studies tried to address the
      potential effect of genetic modifiers on FMF and the potential effect of MEFV
      mutations on other inflammatory diseases. The main points arose from these
      studies include a breakthrough in the therapeutic approach for FMF and the lack
      of consistency regarding the reciprocal effect of MEFV mutations on other
      diseases and the effect of genetic modifiers on FMF. The highlights of these
      studies, their potential clinical implications and the unmet needs, which are
      still to be addressed, are summarised in this review.

PMID- 23009755
TI  - Constitutive overexpression of Norrin activates Wnt/beta-catenin and endothelin-2
      signaling to protect photoreceptors from light damage.
AB  - Norrin is a retinal signaling molecule which is expressed in Muller glia and
      binds to Frizzled-4 to activate canonical Wnt/beta-catenin signaling. Norrin is
      part of an essential signaling system that controls the formation of retinal
      capillaries during development. To evaluate neuroprotective properties of Norrin
      independently from its function during retinal angiogenesis, we generated
      transgenic mice (Rpe65-Norrin) that constitutively express Norrin in the retinal
      pigmented epithelium. Substantial amounts of Norrin were secreted into the outer
      retina, which triggered retinal Wnt/beta-catenin signaling in conjunction with an
      increase in the expression of endothelin-2 (EDN2), endothelin receptor B (EDNRB),
      and glial fibrillary acidic protein (GFAP). Photoreceptors of Norrin
      overexpressing mice were significantly less vulnerable to light-induced damage
      compared to their wild-type littermates. Following light damage, we observed less
      apoptotic death of photoreceptors and a better retinal function than in controls.
      The protective effects were abolished if either Wnt/beta-catenin or EDN2
      signaling was blocked by intravitreal injection of Dickkopf-1 or BQ788,
      respectively. Light-damaged retinae from transgenic mice contained higher amounts
      of brain-derived neurotrophic factor (BDNF) and pAkt than those of wild-type
      littermates. We conclude that constitutive overexpression of Norrin protects
      photoreceptors from light damage, an effect that is mediated by Wnt/beta-catenin
      and EDN2 signaling and involves neurotrophic activities of BDNF. The findings
      suggest that Norrin and its associated signaling pathways have strong potentials
      to attenuate photoreceptor death following injury.

PMID- 23009754
TI  - Stress, caffeine and ethanol trigger transient neurological dysfunction through
      shared mechanisms in a mouse calcium channelopathy.
AB  - Several episodic neurological disorders are caused by ion channel gene mutations.
      In patients, transient neurological dysfunction is often evoked by stress,
      caffeine and ethanol, but the mechanisms underlying these triggers are unclear
      because each has diverse and diffuse effects on the CNS. Attacks of motor
      dysfunction in the Ca(V)2.1 calcium channel mouse mutant tottering are also
      triggered by stress, caffeine and ethanol. Therefore, we used the tottering mouse
      attacks to explore the pathomechanisms of the triggers. Despite the diffuse
      physiological effects of these triggers, ryanodine receptor blockers prevented
      attacks induced by all of them. In contrast, compounds that potentiate ryanodine
      receptors triggered attacks suggesting a convergent biochemical pathway.
      Tottering mouse attacks were both induced and blocked within the cerebellum
      suggesting that the triggers act locally to instigate attacks. In fact, stress,
      caffeine and alcohol precipitated attacks in Ca(V)2.1 mutant mice in which
      genetic pathology was limited to cerebellar Purkinje cells, suggesting that the
      triggers initiate dysfunction within a specific brain region. The surprising
      biochemical and anatomical specificity of the triggers and the discovery that the
      triggers operate through shared mechanisms suggest that it is possible to develop
      targeted therapies aimed at blocking the induction of episodic neurological
      dysfunction, rather than treating the symptoms once provoked.

PMID- 23009753
TI  - Nicotine-mediated improvement in L-dopa-induced dyskinesias in MPTP-lesioned
      monkeys is dependent on dopamine nerve terminal function.
AB  - L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements that develop
      with long term L-dopa therapy for Parkinson's disease. Studies show that nicotine
      administration reduced LIDs in several parkinsonian animal models. The present
      work was done to understand the factors that regulate the nicotine-mediated
      reduction in LIDs in MPTP-lesioned nonhuman primates. To approach this, we used
      two groups of monkeys, one with mild-moderate and the other with more severe
      parkinsonism rendered dyskinetic using L-dopa. In mild-moderately parkinsonian
      monkeys, nicotine pretreatment (300 MUg/ml via drinking water) prevented the
      development of LIDs by ~75%. This improvement was maintained when the nicotine
      dose was lowered to 50 MUg/ml but was lost with nicotine removal. Nicotine re
      exposure again decreased LIDs. By contrast, nicotine treatment did not reduce
      LIDs in monkeys with more severe parkinsonism. We next determined how nicotine's
      ability to reduce LIDs correlated with lesion-induced changes in the striatal
      dopamine transporter and (3)H-dopamine release in these two groups of monkeys.
      The striatal dopamine transporter was reduced to 54% and 28% of control in mild
      moderately and more severely parkinsonian monkeys, respectively. However, basal,
      K(+), alpha4beta2* and alpha6beta2* nAChR-evoked (3)H-dopamine release were near
      control levels in striatum of mild-moderately parkinsonian monkeys. By contrast,
      these same release measures were reduced to a significantly greater extent in
      striatum of more severely parkinsonian monkeys. Thus, nicotine best improves LIDs
      in lesioned monkeys in which striatal dopamine transmission is still relatively
      intact. These data suggest that nicotine treatment would most effectively reduce
      LIDs in patients with mild to moderate Parkinson's disease.

PMID- 23009756
TI  - Nitric oxide and cell death in liver cancer cells.
AB  - Nitric oxide (NO) is a lipophillic, highly diffusible, and short-lived
      physiological messenger which regulates a variety of physiopathological
      responses. NO may exert its cellular action through cGMP-dependent and cGMP
      independent pathways which includes different postranslational modifications. The
      effect of NO in cancer depends on the activity and localization of NOS isoforms,
      concentration and duration of NO exposure, cellular sensitivity, and hypoxia/re
      oxygenation process. NO regulates critical factors such as the hypoxia inducible
      factor-1 (HIF-1) and p53 generally leading to growth arrest, apoptosis or
      adaptation. NO sensitizes hepatoma cells to chemotherapeutic compounds probably
      through increased p53 and cell death receptor expressions.

PMID- 23009758
TI  - School food cost-benefits: England.
AB  - OBJECTIVE: To estimate the costs per relevant unit (pupils and meals) associated
      with improvements to school food and the potential economic and health gains that
      may result. DESIGN: Calculation of costs per relevant unit (pupils and meals)
      based on (i) Department for Education expenditure to support improvements in
      school food, 2005-2011 and (ii) measures of the changes in the number of pupils
      taking school lunch and the number of meals served over the same time period;
      plus examples of the use of linked data to predict longer-term economic and
      health outcomes of healthier eating at school. SETTING: England. SUBJECTS: Local
      authorities, government departments and non-departmental public bodies. RESULTS:
      Analysis of investment over a 6-year period indicates that costs of setting up
      and maintaining a change organization such as the School Food Trust were low in
      relation to short-term benefits in nutrition and behaviour. Models that predict
      long-terms gains to the exchequer and to quality-adjusted life years need further
      elaboration. CONCLUSIONS: Modest levels of government investment in the delivery
      and promotion of healthier school food is likely to yield both short-term and
      long-term benefits in relation to nutrition, learning, economics and health.

PMID- 23009757
TI  - TNF-alpha messenger ribonucleic acid (mRNA) in patients with nonalcoholic
      steatohepatitis.
AB  - BACKGROUND AND AIM: tumor necrosis factor (TNF)-alpha plays a significant role in
      the pathogenesis of nonalcoholic steatohepatitis (NASH). A few studies have
      confirmed high TNF-alpha plasma protein levels in patients with NASH compared to
      healthy volunteers. We herein aimed to revisit these findings using other
      molecular techniques. METHODS: a cross-sectional evaluation of patients newly
      diagnosed with NASH. A quantitative assay for the measurement of TNF-alpha
      messenger ribonucleic acid (mRNA) was performed for NASH patients and controls
      using real-time reverse transcription polymerase chain reaction (RT-PCR).
      RESULTS: in 39 patients with NASH (mean age 38.6 +/- 9.4 years, range 28-60
      years; 79% males), the mean TNF-alpha mRNA level was significantly higher than
      that found for controls (137.6 +/- 102.3 ng/mL versus 83.5 +/- 43.8 ng/mL,
      respectively; P = 0.012). A TNF-alpha mRNA cut-off of 100 ng/mL predicted NASH
      most optimally (AUC 0.685 +/- 0.066, P = 0.01; with 66.7% sensitivity and 74.1%
      specificity). Serum TNF-alpha and soluble TNF-alpha receptor II (sTNFRII) levels
      were significantly higher in patients compared to controls using ELISA.
      CONCLUSION: high TNF-alpha mRNA levels, determined by RT-PCR, characterize
      patients with NASH.

PMID- 23009759
TI  - Emerging trends in Sjogren's syndrome: basic and translational research.
AB  - This review will address the 'state of the art' of novel genomic and proteomic
      biomarkers for primary Sjogren's syndrome (pSS) and the current status and
      potential of gene transfer to salivary glands in restoring the function of
      salivary glands.

PMID- 23009761
TI  - Gut microbiota in preterm infants: assessment and relevance to health and
      disease.

PMID- 23009762
TI  - Design, testing and validation of an innovative web-based instrument to evaluate
      school meal quality.
AB  - OBJECTIVE: To develop a feasible, valid, reliable web-based instrument to
      objectively evaluate school meal quality in Swedish primary schools. DESIGN: The
      construct 'school meal quality' was operationalized by an expert panel into six
      domains, one of which was nutritional quality. An instrument was drafted and
      pilot-tested. Face validity was evaluated by the panel. Feasibility was
      established via a large national study. Food-based criteria to predict the
      nutritional adequacy of school meals in terms of fat quality, iron, vitamin D and
      fibre content were developed. Predictive validity was evaluated by comparing the
      nutritional adequacy of school menus based on these criteria with the results
      from a nutritional analysis. Inter-rater reliability was also assessed. SETTING:
      The instrument was developed between 2010 and 2012. It is designed for use in all
      primary schools by school catering and/or management representatives. SUBJECTS: A
      pilot-test of eighty schools in Stockholm (autumn 2010) and a further test of
      feasibility in 191 schools nationally (spring 2011). RESULTS: The four nutrient
      specific food-based criteria predicted nutritional adequacy with sensitivity
      ranging from 0.85 to 1.0, specificity from 0.45 to 1.0 and accuracy from 0.67 to
      1.0. The sample in the national study was statistically representative and the
      majority of users rated the questionnaire positively, suggesting the instrument
      is feasible. The inter-rater reliability was fair to almost perfect for
      continuous variables and agreement was >= 67 % for categorical variables.
      CONCLUSIONS: An innovative web-based system to comprehensively monitor school
      meal quality across several domains, with validated questions in the nutritional
      domain, is available in Sweden for the first time.

PMID- 23009760
TI  - Cancer cell metabolism: one hallmark, many faces.
AB  - Cancer cells must rewire cellular metabolism to satisfy the demands of growth and
      proliferation. Although many of the metabolic alterations are largely similar to
      those in normal proliferating cells, they are aberrantly driven in cancer by a
      combination of genetic lesions and nongenetic factors such as the tumor
      microenvironment. However, a single model of altered tumor metabolism does not
      describe the sum of metabolic changes that can support cell growth. Instead, the
      diversity of such changes within the metabolic program of a cancer cell can
      dictate by what means proliferative rewiring is driven, and can also impart
      heterogeneity in the metabolic dependencies of the cell. A better understanding
      of this heterogeneity may enable the development and optimization of therapeutic
      strategies that target tumor metabolism.

PMID- 23009763
TI  - Saliva as an ideal milieu for emerging diagnostic approaches in primary Sjogren's
      syndrome.
AB  - This review will summarise the state of the art of salivary diagnostics in
      primary Sjogren's syndrome exploring the potential usefulness of both traditional
      and emerging biotechnologies for primary Sjogren's syndrome non-invasive and
      early detection.

PMID- 23009764
TI  - Interleukin-17A correlates with interleukin-6 production in human cystic
      echinococcosis: a possible involvement of IL-17A in immunoprotection against
      Echinococcus granulosus infection.
AB  - Hydatidosis is a parasitic disease caused by the development, in humans and other
      mammals, of the larval form of Taenia, Echinococcus granulosus. It is one of the
      world's major zoonotic infections. This study aimed to examine interleukin-6 (IL
      6), interferon-gamma (IFN-gamma) and interleukin-17A (IL-17A) production in
      patients with cystic echinococcosis (CE), and the role of IL-17A in the
      modulation of the immune response against the extracellular parasite, E.
      granulosus. A relationship between IL-6, IL-17A production and C reactive Protein
      (CRP) levels was also assessed. IL-6, IFN-gamma, IL-17A and CRP production were
      determined in serum from Algerian hydatid patients. Cytokine production was also
      measured in supernatants from cultures of peripheral blood mononuclear cells
      (PBMCs) from hydatid patients stimulated by a major parasitic antigen (antigen
      5). The increased activity of IL-6, IFN-gamma and IL-17A were observed in most
      serum samples from patients. In contrast, healthy controls showed only minor
      levels. Similarly, high levels of CRP were detected. Our in vitro results
      indicate a positive correlation between IL-6, IFN-gamma and IL-17A production in
      PBMC culture supernatants. However, IL-6, IFN-gamma and IL-17A activity was low
      in serum and supernatants of PBMC cultures from relapsing patients, and there was
      no evidence of an immune response against parasitic antigen. Collectively, our
      results show that IL-17A was produced during human cystic echinococcosis, and was
      involved in the host defense mechanisms against the extracellular parasite E.
      granulosus. Our data suggest that IL-17A plays an immunoprotective role in this
      parasitic, helminth infection.

PMID- 23009766
TI  - Use of point-of-sale data to assess food and nutrient quality in remote stores.
AB  - OBJECTIVE: To examine the feasibility of using point-of-sale data to assess
      dietary quality of food sales in remote stores. DESIGN: A multi-site cross
      sectional assessment of food and nutrient composition of food sales. Point-of
      sale data were linked to Australian Food and Nutrient Data and compared across
      study sites and with nutrient requirements. SETTING: Remote Aboriginal Australia.
      SUBJECT: Six stores. RESULTS: Point-of-sale data were readily available and
      provided a low-cost, efficient and objective assessment of food and nutrient
      sales. Similar patterns in macronutrient distribution, food expenditure and key
      food sources of nutrients were observed across stores. In all stores, beverages,
      cereal and cereal products, and meat and meat products comprised approximately
      half of food sales (range 49-57 %). Fruit and vegetable sales comprised 10.4 (SD
      1.9) % on average. Carbohydrate contributed 54.4 (SD 3.0) % to energy; protein
      13.5 (SD 1.1) %; total sugars 28.9 (SD 4.3) %; and the contribution of total
      saturated fat to energy ranged from 11.0 to 14.4% across stores. Mg, Ca, K and
      fibre were limiting nutrients, and Na was four to five times higher than the
      midpoint of the average intake range. Relatively few foods were major sources of
      nutrients. CONCLUSIONS: Point-of-sale data enabled an assessment of dietary
      quality within stores and across stores with no burden on communities and at no
      cost, other than time required for analysis and reporting. Similar food spending
      patterns and nutrient profiles were observed across the six stores. This suggests
      potential in using point-of-sale data to monitor and evaluate dietary quality in
      remote Australian communities.

PMID- 23009765
TI  - Behcet's disease: features of neurological involvement in a dedicated centre in
      Italy.
AB  - OBJECTIVES: The aim of the present study was to retrospectively assess the
      prevalence of neurological involvement and the clinical patterns of presentation
      in a monocentric cohort of patients with BD, who have been followed in the last
      twenty years at our centre. METHODS: One hundred and seventeen patients were
      retrospectively studied. The male/female ratio was 1.6:1, with a mean disease
      duration of 11+/-5 years. Their mean age was 42+/-9 years (min:18, max:77), while
      the mean age at disease onset was 25+/-4 years (min:10, max:58). The mean +/- SD
      duration of follow-up at our centre was 7+/-2 (min:1, max:11) years. RESULTS:
      Neurological involvement was observed in 38% (44 patients, 36 males and 8
      females; mean age at onset 25+/-4 years). Organic brain involvement, demonstrated
      by MRI was due to ischaemic pons-mesencephalon lesions in 19 patients and to
      meningoencephalitis with brainstem involvement in 16. Peripheral nervous system
      involvement was confirmed by electroneuromyographic study in 4 patients, and
      consisted of peripheral neuropathy prominent in the lower extremities in all
      cases; we have also observed only 2 cases of endocranial hypertension and 3 BD
      patients suffering from pulsatile, severe headache, without abnormal neurological
      examination, responding only to medium-high doses of steroids. Excluding
      peripheral neuropathy and isolated headache, the onset of CNS involvement (total
      prevalence: 32% of the cohort) was observed in 2 patients within the first year
      from the onset of BD, in 4 cases between the first and the third year, in 24
      between the third and the fifth year, 7 between the fifth and the tenth year;
      none presented a CNS involvement after the first 10 years of disease.
      CONCLUSIONS: Neuro-BD is more frequent in young males and it never represents a
      presenting feature of the disease. The most frequent time of onset of
      neurological involvement seems to be within the first 10 years of disease. Since
      neurological involvement may result in severe functional disability or be a life
      threatening disease, a careful follow-up during the first years after onset is
      recommended.

PMID- 23009767
TI  - Magnesium and Gitelman's syndrome: a paradox awaiting resolution.

PMID- 23009768
TI  - Coherent picosecond exciton dynamics in a photosynthetic reaction center.
AB  - Photosynthetic reaction centers convert sunlight into a transmembrane
      electrochemical potential difference, providing chemical energy to almost all
      life on earth. Light energy is efficiently transferred through chromophore
      cofactors to the sites, where charge separation occurs. We applied two
      dimensional electronic spectroscopy to assess the role of coherences in the
      photoresponse of the bacterial reaction center of  Rhodobacter sphaeroides.  By
      controlling the polarization of the laser beams, we were able to assign
      unambiguously the oscillatory dynamics to electronic (intermolecular) coherences.
      The data show that these coherences are sustained for more than 1 ps, indicating
      that the protein coherently retains some excitation energy on this time scale.
      Our finding provides a mechanism for effective delocalization of the excitations
      on the picosecond time scale by electronic coherence, setting the stage for
      efficient charge separation.

PMID- 23009769
TI  - Reduced efficacy of the intravenous anesthetic agent AZD3043 at GABA(A) receptors
      with beta2 (N289M) and beta3 (N290M) point-mutations.
AB  - AZD3043 (previously named THRX-918661) is a novel short-acting intravenous
      anesthetic agent in clinical trials. Although AZD3043 is a positive modulator at
      the gamma-aminobutyric acid (GABA)(A)-receptor, its potency and efficacy have not
      been characterized in detail. Nor is it known whether the point-mutations in the
      beta-subunit of the GABA(A)-receptor that dramatically reduce the anesthetic
      effect of propofol (i.e. beta2 (N289M) and beta3 (N290M)), also influence the
      effect of AZD3043. This study investigated the in vitro pharmacology of AZD3043
      at the most common human GABA(A) receptor subtypes. Subunits of four human wild
      type (alpha1beta2, alpha1beta2gamma2, alpha2beta2gamma2 and alpha2beta3gamma2)
      and two mutant (alpha1beta2(N289M)gamma2 and alpha2beta3(N290M)gamma2) GABA(A)
      receptor channels were introduced into Xenopus oocytes and studied with two
      electrode voltage-clamp. AZD3043 potentiated and directly activated the
      alpha1beta2gamma2, alpha2beta2gamma2 and alpha2beta3gamma2 GABA(A) receptor
      subtypes. Moreover, both potency and efficacy of AZD3043 were reduced at the
      mutant alpha1beta2(N289M)gamma2 and alpha2beta3(N290M)gamma2 subtypes. AZD3043
      increased the GABA response also in GABA(A) receptors lacking the gamma2-subunit,
      i.e. alpha1beta2. In conclusion, AZD3043 is a positive modulator and a direct
      agonist at human GABA(A) receptors and is not dependent on the gamma2-subunit for
      its effect. Similar to propofol, the effect of AZD3043 is dramatically reduced by
      point-mutations in the beta2(N289M) and beta3(N290M) subunits, indicating similar
      molecular mechanisms of action for propofol and AZD3043 at the human GABA(A)
      receptor.

PMID- 23009770
TI  - Thoracic radiologic manifestations of melioidosis.
AB  - Melioidosis (Burkholderia pseudomallei) is a gram-negative bacterial infection
      that is highly endemic in Southeast Asia and Oceania. Pulmonary disease is the
      most common form of involvement. The clinical-radiologic thoracic manifestations
      of melioidosis can be classified as acute, subacute, subclinical, and chronic
      forms. Radiographic findings include nodular, alveolar, or mixed
      infiltration/consolidation with or without cavities. Pleural effusion,
      pneumothorax, and pericardial involvement can be seen. Melioidosis can easily be
      confused with other infections, especially tuberculosis. Suspicion of this
      disease in the proper clinical radiologic setting is important for early
      diagnosis and treatment. In this article, we provide a broad clinical overview of
      melioidosis, review the radiologic thoracic manifestations of melioidosis with
      appropriate clinical correlation, as well as compare and contrast the imaging
      findings of thoracic melioidosis with other similar pulmonary infections.

PMID- 23009771
TI  - Teratomas: a multimodality review.
AB  - Germ cell tumors (GCTs) may occur in both children and adults and include a broad
      array of histologic subtypes, such as teratoma, seminoma (known as dysgerminoma
      in the ovary and germinoma in the pineal gland), choriocarcinoma, yolk sac tumor,
      embryonal cell carcinoma, and mixed GCT. In adults, GCTs occur most commonly in
      the gonads. In children, sacrococcygeal tumors predominate. Teratomas are a
      common form of GCT. They are defined histologically as containing tissues derived
      from all 3 germ cell layers: ectoderm, mesoderm (most teratomas contain fat, an
      imaging hallmark, which is a mesodermal derivative), and endoderm. Teratomas are
      also classified as mature or immature, depending on the degree of differentiation
      of its components, and in adults, immature tumors are more likely to exhibit
      malignant behavior.

PMID- 23009772
TI  - Anorectal opportunistic diseases in human immunodeficiency virus/acquired
      immunodeficiency syndrome patients: spectrum of cross-sectional imaging findings.
AB  - Patients infected with the human immunodeficiency virus, particularly male
      homosexuals, are prone to develop disorders involving the anorectal and perineal
      structures. Cross-sectional imaging techniques, such as multidetector computed
      tomography with multiplanar reformations and magnetic resonance imaging performed
      with phased-array coils, are increasingly adopted to detect and stage infectious
      and neoplastic diseases, and to assess posttreatment modifications. Pyogenic
      perianal sepsis may be usefully investigated with imaging, particularly to assess
      the presence and topography of abscess collections to allow a correct surgical
      choice. Rectal inflammatory involvement is frequently detected during intestinal
      opportunistic infections, such as cytomegalovirus, pseudomembranous, and amebic
      colitides, including primary and secondary imaging signs consistent with
      proctocolitis. Anal carcinoma and intestinal lymphoma are increasingly diagnosed;
      therefore, special attention should be paid to the identification of solid tissue
      consistent with tumor; furthermore, MRI provides optimal staging and
      posttreatment follow-up of neoplastic lesions. Knowledge of this varied spectrum
      of anorectal and perineal opportunistic abnormalities and their imaging
      appearances should help radiologists to propose appropriate differential
      diagnoses, suggest correlation with laboratory and microbiological assays or
      biopsy, and reliably assess therapeutic response.

PMID- 23009774
TI  - From the editor: the enigma of hypertriglyceridemia.

PMID- 23009773
TI  - Hemorrhagic complications of anticoagulant therapy: role of multidetector
      computed tomography and spectrum of imaging findings from head to toe.
AB  - Highly effective in preventing and treating thromboembolic conditions in acute
      and chronic settings, anticoagulant therapy is associated with a non-negligible
      risk of hemorrhagic complications with a considerable clinical impact. Advanced
      age and comorbidities further increase the risk of bleeding during
      heparinization, treatment with low-molecular-weight heparins or long-term oral
      warfarin anticoagulation. Multidetector computed tomography represents the
      mainstay diagnostic technique to image-suspected hemorrhages in anticoagulated
      patients, as it can quickly assess presence, site, and extent of hemorrhage,
      identify active bleeding, and possible underlying diseases. Cross-sectional
      imaging appearances of the wide spectrum of anticoagulant therapy-related
      bleeding complications are hereby presented, including peripheral and thoracic
      abdominal wall muscular hematomas, intrathoracic, abdominal, retroperitoneal
      genitourinary, gastrointestinal, and brain hemorrhages. Prompt recognition and
      comprehensive diagnostic assessment with multidetector computed tomography allow
      clinicians to correctly choose treatment modification or withdrawal, surgery, or
      interventional procedures as needed, with the aim to reduce the associated
      morbidity and mortality.

PMID- 23009775
TI  - Severe hypertriglyceridemia.

PMID- 23009776
TI  - The interaction of familial and secondary causes of hypertriglyceridemia: role in
      pancreatitis.

PMID- 23009777
TI  - Treatment options for the management of hypertriglyceridemia: strategies based on
      the best-available evidence.
AB  - A severe elevation in triglycerides (TG; >=500 mg/dL) increases the risk for
      pancreatitis. TG levels >=200 mg/dL are associated with a greater risk of
      atherosclerotic coronary heart disease (CHD). However, no outcomes trials exist
      to assess the efficacy of TG lowering for preventing pancreatitis in patients
      with severe hypertriglyceridemia. Similarly, no completed prospective outcomes
      trial exists to support or refute a reduction in CHD risk resulting from lipid
      altering therapy in patients specifically selected for the presence of
      hypertriglyceridemia. This review examines the available evidence for the use of
      statins, omega-3 fatty acids, fibrates, and niacin in the management of
      hypertriglyceridemic patients. Results from CHD outcomes trials support statins
      as the first-line lipid-altering drug therapy to reduce CHD in
      hypercholesterolemic patients, and subgroup analyses suggest statins are
      efficacious in hypertriglyceridemic patients with fasting TG levels <500 mg/dL.
      Omega-3 fatty acids and fibrates are reasonable first drug options for patients
      with TG >=500 mg/dL and often are used to lower TG levels with the objective of
      reducing pancreatitis risk, although a statin or niacin may also be reasonable
      options. Combination lipid drug therapy may be needed to achieve both low-density
      lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment
      goals for CHD prevention in patients with elevated TG levels, particularly those
      with TG >=500 mg/dL. Additional clinical outcomes data are needed to provide a
      more evidence-based rationale for clinical lipid management of
      hypertriglyceridemic patients.

PMID- 23009778
TI  - Phenotypes of hypertriglyceridemia caused by excess very-low-density lipoprotein.
AB  - OBJECTIVE: To characterize the composition of very-low-density lipoprotein (VLDL)
      particles and the proportion of VLDL to total apolipoprotein B (apoB) particles
      in patients with hypertriglyceridemia caused by excess VLDL. METHODS: Subjects
      were selected from 2023 consecutive patients attending the Lipid Clinic at the
      Laval University Centre. Plasma lipids, apoB, and apoA-I were measured and
      chylomicron lipids and VLDL and LDL lipids and apoB determined after
      ultracentrifugation. Patients with hypertriglyceridemia caused by excess VLDL
      were divided into four groups on the basis of triglyceride and apoB. RESULTS: A
      total of 440 controls, 387 subjects with normotriglyceridemic hyperapoB, 38 with
      type III dysbetalipoproteinemia, 270 with mild hypertriglyceridemic normoapoB,
      163 with moderate hypertriglyceridemic normoapoB, 458 with mild
      hypertriglyceridemic hyperapoB, and 295 subjects with moderate
      hypertriglyceridemic hyperapoB were compared. In patients with
      hypertriglyceridemia caused by excess VLDL, the VLDL particles were triglyceride
      and cholesterol-enriched. HyperapoB is associated with greater low-density
      lipoprotein (LDL) apoB than normoapoB, whereas greater triglycerides are
      associated with greater VLDL apoB. Thus, the ratio of VLDL apoB/total apoB was
      significantly less in those with mild hypertriglyceridemia compared with those
      with moderate hypertriglyceridemia, irrespective of the plasma apoB. CONCLUSIONS:
      The apoB phenotypes in hypertriglyceridemia caused by excess VLDL appear to be
      determined by the extent to which VLDL secretion increases, the extent to which
      VLDL particles can be converted to LDL particles, and the effects of core lipid
      exchange. More accurate characterization of hypertriglyceridemia caused by excess
      VLDL should lead to a better understanding of the determinants of VLDL clearance
      and conversion to LDL as well as of the atherogenic potential of VLDL.

PMID- 23009779
TI  - Hypertriglyceridemia and residual dyslipidemia in statin-treated, patients with
      diabetes at the highest risk for cardiovascular disease and achieving very-low
      low-density lipoprotein-cholesterol levels.
AB  - BACKGROUND: As the result of the high prevalence of comorbidities and
      conventional risk factors among patients with type 2 diabetes (T2DM), most
      patients belong to the highest cardiovascular disease risk category, and have a
      target low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL. Because
      substantial residual risk persists at LDL-C <70 mg/dL, a more comprehensive
      control of non-LDL-C and particles was recommended in the joint 2008 American
      Diabetes Association/American College of Cardiology Consensus. OBJECTIVE: To
      ascertain, in statin-treated T2DM patients belonging to this greatest-risk group,
      with on-statin LDL-C <70 mg/dL, (1) the proportion of patients meeting all three
      critical levels (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol [HDL
      C] <100 mg/dL, apoB <80 mg/dL) and (2) the variables associated with target
      attainment versus nonattainment. PATIENTS AND METHODS: Among 675 unselected
      patients with T2DM, 367 were both at very high cardiometabolic risk and taking
      statins; 118 of these patient had LDL-C levels <70 mg/dL. Patients meeting all
      three criteria (LDL-C, non-HDL-C, and apoB; n = 79; all three at goal group) were
      compared with those only reaching LDL-C (n = 49; only LDL-C at goal group).
      RESULTS: LDL-C was 54 (12) for the all three at goal group versus 57 (10) mg/dL
      for the only LDL-C at goal group (NS). The two groups were similar regarding age,
      gender, diabetes duration, body mass index, waist circumference, blood pressure,
      renal function and micro-/macroangiopathy prevalence. A statin plus fibrate was
      given to 16% of patients in the all three at goal group and 32% in the only LDL-C
      at goal group. The two groups did not differ in baseline (prestatin) LDL-C, HDL
      C, and non-HDL-C, except for pre-/post-lipid-lowering drug(s) triglycerides (TG):
      177 (95)/118 (56) for all three at goal versus 279 (134)/ 241 (103) mg/dL for
      only LDL-C at goal (P = .0230 and P = .0001). The only LDL-C at goal group had
      lower HDL-C (vs. all three at goal): 41 (12) vs. 47 (14) mg/dL (P = .0237), with
      atherogenic dyslipidemia [hypo-HDL-C + hyper-TG] prevalence of 35% in the all
      three at goal versus 56% in the only LDL-C at goal group (P < .0001). log(TG)/HDL
      C was 0.049 (0.021) for all three at goal versus 0.063 (0.021) for only LDL-C at
      goal (P < .0001). The LDL-C/apoB ratio was 0.92 (0.24) for all three at goal vs.
      0.67 (0.18) for only LDL-C at goal (P < .0001), suggestive of smaller/denser LDL.
      CONCLUSION: The presence of atherogenic dyslipidemia was associated with a
      failure to meet all three critical modifiable targets for hypercholesterolemia,
      such a nonachievement being found in a large proportion (one-third) of very-high
      risk T2DM patients with very-low on-statin LDL-C. Attainment of all three targets
      will require (1) titration/permutation of statins, (2) lifestyle (re)inforcement;
      and/or (3) statin-fibrate bitherapy.

PMID- 23009780
TI  - Hospital use and medical care costs up to 5 years after triglyceride lowering
      among patients with severe hypertriglyceridemia.
AB  - BACKGROUND: Severe hypertriglyceridemia is associated with resource-intensive
      conditions such as cardiovascular disease, diabetes, and pancreatitis. Whether
      triglyceride (TG) reduction reduces annual medical costs has not been studied.
      OBJECTIVE: The objective was to compare medical care costs after changes in
      triglyceride levels for up to 5 years of follow-up. METHODS: Using an
      observational cohort, we identified 808 individuals who had a baseline TG level
      >=500 mg/dL in calendar year 2004 and had a second measure 6 to 24 weeks later.
      We collected all subsequent inpatient, outpatient, and pharmacy use and medical
      cost data through 2009. Percentage change from baseline TG level was used to
      create six categories: decreased >=60%, 45%-59%, 30%-44%, 15%-29%, 0%-14%, and TG
      increase. We estimated and compared annualized medical care costs by adjusting
      for baseline costs, baseline TG, high-density lipoprotein, and low-density
      lipoprotein cholesterol levels, age, sex, smoking status, body mass index, blood
      pressure, and presence of comorbidities such as diabetes and cardiovascular
      disease. RESULTS: Mean age of the cohort was 55.9 +/- 11.7 years and 66% were
      men. Patients who reduced their TG levels by >=60% experienced a mean annualized
      reduction from baseline medical costs of $471, whereas costs increased in all
      other TG change categories. Between-group differences were most pronounced in the
      first three years, but none were statistically significant. CONCLUSION: This
      observational study was unable to establish that TG lowering among patients with
      severe hypertriglyceridemia produced statistically significantly lower hospital
      use or medical care costs. However, the nonsignificant trends observed suggest
      that a larger study conducted with controlled TG lowering may be warranted.

PMID- 23009781
TI  - Clinical and economic benefits observed when follow-up triglyceride levels are
      less than 500 mg/dL in patients with severe hypertriglyceridemia.
AB  - BACKGROUND: Increased levels of triglycerides are associated with an increased
      risk of cardiovascular disease and pancreatitis. In this study we investigated
      the association between patients with severely increased triglycerides whose
      follow-up triglyceride levels were <500 mg/dL and reduction of important clinical
      events and associated health care costs. METHODS: By using two large U.S. health
      care claims databases, we identified an initial cohort of 41,210 patients with
      severe hypertriglyceridemia between June 2001 and September 2010 who had a follow
      up laboratory test result 6 to <24 weeks after the initial severe
      hypertriglyceridemia laboratory value. Of these, 8493 patients' follow-up
      triglyceride levels remained elevated (>=500 mg/dL) whereas 32,717 were <500
      mg/dL. After their qualifying follow-up triglyceride level, patients'
      cardiovascular events, diabetes-related events, pancreatitis episodes, kidney
      disease, and related costs were identified. Adjusted incidence rate ratios with
      the use of Cox proportional hazards models were developed for each outcome.
      RESULTS: Patients whose triglycerides remained >=500 mg/dL had a greater rate of
      pancreatitis episodes (hazard ratio [HR]1.79; 95% confidence interval [CI] 1.47
      2.18), cardiovascular events (HR1.19; 95% CI 1.10-1.28), diabetes-related events
      (HR1.42; 95% CI 1.27-1.59), and kidney disease (HR1.13; 95% CI 1.04-1.22)
      compared with patients whose follow-up triglycerides were <500 mg/dL, after we
      adjusted for important confounders. Adjusted all-cause total and cardiovascular
      related costs were significantly lower in the first 3 years in patients whose
      follow-up triglyceride levels were <500 mg/dL compared with those whose
      triglyceride levels remained increased. CONCLUSION: When follow-up triglyceride
      levels were <500 mg/dL, we observed an associated reduction in the risk of
      clinical events and decrease in health care resource use and costs.

PMID- 23009782
TI  - Serum apolipoprotein A-V in patients with coronary artery disease and its
      association with triglyceride.
AB  - BACKGROUND: Apolipoprotein A-V (ApoA-V) has been shown to play an important role
      in the metabolism of plasma triglyceride (TG) levels. However, data for the
      relationship between serum ApoA-V and TG level and the association between ApoA-V
      levels and the risk of coronary artery disease (CAD) are inconsistent. OBJECTIVE:
      To investigate plasma ApoA-V level and its association with TG in patients with
      CAD determined by angiography. METHODS: Three hundred forty subjects who
      underwent coronary angiography (CAG) were classified into a CAD group (n = 211)
      and a non-CAD group (n = 129) according to the results of their CAG. Serum ApoA-V
      levels were determined by enzyme-linked immunosorbent assays. RESULTS: Patients
      in the CAD group had greater ApoA-V levels than controls (192.0 +/- 114.6 ng/mL
      vs 164.4 +/- 107.5 ng/mL, P < .05). The concentration of ApoA-V was positively
      correlated to TG level (r = 0.229, P < .01). This correlation was more intense in
      non-CAD group (r = 0.306, P < .01) than in CAD group (r = 0.172, P < .05). ApoA-V
      was positively associated with Gensini score. However, the contribution of ApoA-V
      to Gensini score and CAD risk disappeared after adjustment for the TG level.
      CONCLUSION: The positive correlation between serum ApoA-V and TG differs in
      strength between control and CAD patients. The correlation between ApoA-V and CAD
      is confounded by the effect of TG. We speculate that the increase of ApoA-V may
      be a consequence of compensation for the increased demand for plasma TG
      hydrolysis.

PMID- 23009783
TI  - Pseudohypertriglyceridemia: two cases of probable glycerol kinase deficiency.
AB  - The National Cholesterol Educational Program Adult Treatment Panel's third report
      define borderline-high, high, and very high triglycerides as serum levels of 150
      199 mg/dL, 200-499 mg/dL, and >=500 mg/dL, respectively. Hypertriglyceridemia
      (HTG) is generally very responsive to both therapeutic lifestyle changes (TLC),
      and drug therapy, with niacin, omega-3 fatty acids, fibrates, and statins, each
      reducing levels by ~10-50%. This paper presents two cases of patients who were
      aggressively treated for significant HTG with little response to therapy.
      Although most measured triglyceride (TG) values in these patients were markedly
      elevated, periodic concentrations were reported as normal. When this occurs, the
      clinician must immediately think of the diagnosis 'pseudohypertriglyceridemia' or
      as it is more aptly termed 'glycerolemia' secondary to glycerol kinase deficiency
      (GKD).

PMID- 23009784
TI  - Plasma exchange for severe hypertriglyceridemia-induced pancreatitis in an
      orthotopic heart transplant recipient.
AB  - We here report a 33-year old male with diabetes, hypertension and history of
      orthotopic heart transplantation treated by plasma exchange for severe HTG
      (hypertriglyceridemia) induced pancreatitis. At the time of presentation, his
      serum TG (triglyceride) level was 10,278 mg/dL. He underwent one of the three
      planned sessions of plasma exchange, resulting in a decrease in TG level from
      4728 mg/dL to 1708 mg/dL. The hospital course was complicated with shock,
      hemorrhagic transformation of the pancreatitis and acute respiratory distress
      syndrome. This prevented any further plasma exchange sessions. He was
      subsequently discharged home in a stable state and TG level of 80 mg/dL. Plasma
      exchange can be safely used to manage HTG induced pancreatitis in heart
      transplant recipients.

PMID- 23009786
TI  - EPA and DHA: distinct yet essential n-3 fatty acids.

PMID- 23009787
TI  - Lifetime experiences, the brain and personalized medicine: an integrative
      perspective.
AB  - The aim of personalized medicine is to base medical prevention and therapy on the
      unique health and disease susceptibility profile of each individual. Starting
      from this idea, we briefly discuss the meaning of the word 'personalized' before
      analyzing the practical content of personalized healthcare. From a medical
      perspective, knowledge of a person encompasses both biological and biographical
      perspectives. The latter includes significant events and experiences throughout
      the person's lifespan, from conception to the present, in which epigenetic
      influences play an important role. In practice, we believe personalized medicine
      should emphasize the development and maintenance of a healthy nervous system. The
      neurobiological processes involved here depend heavily on the psychosocial
      environment, in particular the presence of responsible, caring adults and
      integration in a reasonably fair society. A healthy brain subsequently promotes
      good health throughout life, both through direct, favorable influences on the
      body's intrinsic biological pathways, and indirectly by enabling the person to
      engage in supportive relationships, make wise decisions and take good care of
      him/herself. From a public health perspective, we conclude that hi-tech
      personalized medicine based on detailed bio-molecular mapping, monitoring and
      tailored drug interventions holds promise only as part of a wider, socio
      culturally informed approach to the person.

PMID- 23009788
TI  - Evaluation of BTEX and phenol removal from aqueous solution by multi-solute
      adsorption onto smectite organoclay.
AB  - The removal process of BTEX and phenol was evaluated. The smectite organoclay for
      single-solute system reached removal was evaluated by adsorption on smectite
      organoclay adsorbent by kinetic and equilibrium efficiencies between 55 and 90%
      while was reached between 30 and 90% for multi-solute system at 297 K and pH 9.
      The Langmuir-Freundlich model was used to fit the experimental data with
      correlation coefficient between 0.98 and 0.99 providing kinetic and equilibrium
      parameter values. Phenol and ethylbenzene presented high maximum adsorbed amount,
      8.28 and 6.67 mg/g, respectively, compared to the other compounds for single
      solute. Toluene and p-xylene presented high values of adsorption constant which
      indicates a high adsorption affinity of compounds to organoclay surface and high
      binding energy of adsorption. Phenol presented low kinetic adsorption constant
      value indicating slow rate of adsorption.

PMID- 23009789
TI  - Effect of surface modification on single-walled carbon nanotube retention and
      transport in saturated and unsaturated porous media.
AB  - This work investigated the effect of different surface modification methods,
      including oxidization, surfactant coating, and humic acid coating, on single
      walled carbon nanotube (SWNT) stability and their mobility in granular porous
      media under various conditions. Characterization and stability studies
      demonstrated that the three surface modification methods were all effective in
      solubilizing and stabilizing the SWNTs in aqueous solutions. Packed sand column
      experiments showed that although the three surface medication methods showed
      different effect on the retention and transport of SWNTs in the columns, all the
      modified SWNTs were highly mobile. Compared with the other two surface
      modification methods, the humic acid coating method introduced the highest
      mobility to the SWNTs. While reductions in moisture content in the porous media
      could promote the retention of the surface modified SWNTs in some sand columns,
      results from bubble column experiment suggested that only oxidized SWNTs were
      retention in unsaturated porous media through attachment on air-water interfaces.
      Other mechanisms such as grain surface attachment and thin-water film straining
      could also be responsible for the retention of the SWNTs in unsaturated porous
      media. An advection-dispersion model was successfully applied to simulate the
      experimental data of surface modified SWNT retention and transport in porous
      media.

PMID- 23009790
TI  - In vitro assessment on the impact of soil arsenic in the eight rice varieties of
      West Bengal, India.
AB  - Rice is an efficient accumulator of arsenic and thus irrigation with arsenic
      contaminated groundwater and soil may induce human health hazard via water-soil
      plant-human pathway. A greenhouse pot experiment was conducted on three high
      yielding, one hybrid and four local rice varieties to investigate the uptake,
      distribution and phytotoxicity of arsenic in rice plant. 5, 10, 20, 30 and 40 mg
      kg(-1) dry weights arsenic dosing was applied in pot soil and the results were
      compared with the control samples. All the studied high yielding and hybrid
      varieties (Ratna, IET 4094, IR 50 and Gangakaveri) were found to be higher
      accumulator of arsenic as compared to all but one local rice variety, Kerala
      Sundari. In these five rice varieties accumulation of arsenic in grain exceeded
      the WHO permissible limit (1.0 mg kg(-1)) at 20 mg kg(-1) arsenic dosing.
      Irrespective of variety, arsenic accumulation in different parts of rice plant
      was found to increase with increasing arsenic doses, but not at the same rate. A
      consistent negative correlation was established between soil arsenic and
      chlorophyll contents while carbohydrate accumulation depicted consistent positive
      correlation with increasing arsenic toxicity in rice plant.

PMID- 23009791
TI  - Effects of ozone and ozone/peroxide pretreatments on disinfection byproduct
      formation during subsequent chlorination and chloramination.
AB  - Ozone (O3) and ozone/hydrogen peroxide (O3/H2O2) can be used in water treatment
      facilities to remove many organic micropollutants with taste, odor, and color
      implications. The effects of O3 and O3/H2O2 on the formation of disinfection
      byproducts (DBPs) in subsequent chlorination and chloramination processes,
      however, are not well determined. In this study, we compared the yields of a
      series of regulated and emerging DBPs during sequenced O3-Cl2, O3/H2O2-Cl2, O3
      NH2Cl, and O3/H2O2-NH2Cl oxidation of 11 samples, each with different
      hydrophobicity, bromide concentration, soluble microbial products, and humic
      substances. For most water, pretreatment with O3 and O3/H2O2 increased the
      formation of chloral hydrate (CH), trichloronitromethane (TCNM) and haloketones
      (HKs) but lowered the yields of haloacetonitriles (HANs) during chlorination
      processes. Compared with O3 alone, O3/H2O2 in combination generated more CH and
      HKs during chlorination, and their extents of formation appeared to depend on the
      O3 doses. In terms of chloramination, both O3 and O3/H2O2 reduced THM, HAA, and
      HAN formation significantly without increasing CH, TCNM, or HKs. These results
      suggest that O3 or O3/H2O2 pretreatments may provide some benefits for the
      chloramination process in controlling regulated and emerging DBPs in waters
      without high bromide content.

PMID- 23009792
TI  - Evaluation of optimal reuse system for hydrofluoric acid wastewater.
AB  - The treatment of hydrofluoric acid (HF) wastewater has been an important
      environmental issue in recent years due to the extensive use of hydrofluoric acid
      in the chemical and electronics industries, such as semiconductor manufacturers.
      Coagulation/precipitation and ion exchange technologies have been used to treat
      HF wastewater, but these conventional methods are ineffective in removing
      organics, salts, and fluorides, limiting its reuse for water quality and economic
      feasibility. One promising alternative is reverse osmosis (RO) after lime
      treatment. Based on pilot-scale experiment using real HF wastewater discharged
      from semiconductor facility, the spiral wound module equipped with polyamide
      membranes has shown excellent flux and chemical cleaning cycles. Our results
      suggest that coagulation/precipitation and spiral wound RO constitute the optimal
      combination to reuse HF wastewater.

PMID- 23009793
TI  - Catalytic ozonation of metolachlor under continuous operation using nanocarbon
      materials grown on a ceramic monolith.
AB  - The catalytic ozonation of the herbicide metolachlor (MTLC) was tested using
      carbon nanomaterials as catalysts. Multiwalled carbon nanotubes were used in semi
      batch experiments and carbon nanofibres grown on a honeycomb cordierite monolith
      were tested in continuous experiments. The application of the carbon catalyst was
      shown to improve the mineralization degree of MTLC and to decrease the toxicity
      of the solution subject to ozonation. Degradation by-products were also followed
      in order to compare the two processes. The application of the carbon coated
      monolith to the continuous ozonation process was shown to have potential as it
      improved the TOC removal from 5% to 35% and decreased the inhibition of
      luminescent activity of Vibrio Fischeri from 25% to 12%.

PMID- 23009794
TI  - Effective adsorption of hexavalent chromium through a three center (3c) co
      operative interaction with an ionic liquid and biopolymer.
AB  - Biopolymers as well as ionic liquids are known for their potential applications.
      In this work, we report the utility of chitosan as an excellent platform for
      impregnating the ionic liquid, tetraoctylammonium bromide by ultrasonication and
      its subsequent adsorption for chromium(VI). The effective mass transfer due to
      sonication coupled with the hydrogen bonding interaction between chitosan-ionic
      liquid and the electrostatic interaction involving the amino groups in chitosan
      and hexavalent chromium governs this three center (3c) co-operative mechanism.
      The adsorption followed a pseudo second order kinetics with a Langmuir adsorption
      capacity of 63.69 mg g(-1). Various isotherm models were used to correlate the
      experimental data and the adsorption process is exothermic with a decreased
      randomness at the solid-solution interface. The thermodynamics of the spontaneous
      adsorption process could be explained through a positive co-operative effect
      between the host (chitosan) and the guest (ionic liquid). The adsorbed
      chromium(VI) could be converted to ammonium chromate using ammonium hydroxide,
      thereby regenerating the adsorbent. The method could be translated into action in
      the form of practical application to a real sample containing chromium.

PMID- 23009795
TI  - Comparing the joint effect of arsenic exposure, cigarette smoking and risk
      genotypes of vascular endothelial growth factor on upper urinary tract urothelial
      carcinoma and bladder cancer.
AB  - Arsenic exposure and cigarette smoking are environmental risk factors for
      urothelial carcinoma (UC). Vascular endothelial growth factor (VEGF) is the key
      regulator of angiogenesis in various malignancies. This study investigates the
      joint effect of arsenic exposure, cigarette smoking, and VEGF polymorphisms on UC
      risk. This was a hospital-based case-control study consisting of 730
      histopathologically confirmed UC cases, including 470 bladder cancers, 260 upper
      urinary tract UCs (UUTUCs), and 850 age-matched controls, recruited from
      September 1998 to December 2009. UC risk was estimated by odds ratios and 95%
      confidence intervals using unconditional logistic regression. Ever smokers with
      high arsenic exposure had significantly increased risks of 5.7 and 6.4 for
      bladder cancer and UUTUC, respectively. Moreover, ever smokers with high arsenic
      exposure carrying 1 or 2 risk genotypes of the VEGF gene had a significantly
      increased risk of 6.6 for bladder cancer and a strikingly higher risk of 9.9 for
      UUTUC. Additionally, UUTUC cases with high arsenic exposure carrying 1 or 2 risk
      genotypes of the VEGF gene had a non-significant increased risk of advanced tumor
      stage. Our findings suggest that arsenic exposure, cigarette smoking, and risk
      genotypes of VEGF contribute to a higher risk of UUTUC than of bladder cancer. 

PMID- 23009796
TI  - Catalytic ozonation of sulphamethoxazole in the presence of carbon materials:
      catalytic performance and reaction pathways.
AB  - Two carbon materials (multi-walled carbon nanotubes, MWCNTs, and activated
      carbon) were investigated as ozonation catalysts for the mineralization of the
      antibiotic sulphamethoxazole (SMX). MWCNTs presented a higher catalytic
      performance than activated carbons, which was justified by their differences in
      surface chemistry and by the higher internal mass transfer resistances expected
      for activated carbons. 3-Amino-5-methylisoxazole and p-benzoquinone were detected
      as primary products of single and catalytic ozonation of SMX, whereas oxamic,
      oxalic, pyruvic and maleic acids were identified as refractory final oxidation
      products. The original sulphur of the SMX was almost completely converted to
      sulphate and part of the nitrogen was converted to NH4+ and NO3-. The presence of
      the radical scavenger tert-butanol during catalytic and single ozonation
      evidenced the participation of HO radicals in the oxidation mechanisms of SMX,
      especially in the mineralization of several intermediates. Microtox tests
      revealed that simultaneous use of ozone and MWCNTs originated lower acute
      toxicity. The time course of all detected compounds was studied and the
      transformation pathway for the complete mineralization of SMX by single and
      catalytic ozonation in the presence of the selected materials was elucidated.

PMID- 23009797
TI  - Azo dye removal in a membrane-free up-flow biocatalyzed electrolysis reactor
      coupled with an aerobic bio-contact oxidation reactor.
AB  - Azo dyes that consist of a large quantity of dye wastewater are toxic and
      persistent to biodegradation, while they should be removed before being
      discharged to water body. In this study, Alizarin Yellow R (AYR) as a model azo
      dye was decolorized in a combined bio-system of membrane-free, continuous up-flow
      bio-catalyzed electrolysis reactor (UBER) and subsequent aerobic bio-contact
      oxidation reactor (ABOR). With the supply of external power source 0.5 V in the
      UBER, AYR decolorization efficiency increased up to 94.8+/-1.5%. Products
      formation efficiencies of p-phenylenediamine (PPD) and 5-aminosalicylic acid (5
      ASA) were above 90% and 60%, respectively. Electron recovery efficiency based on
      AYR removal in cathode zone was nearly 100% at HRTs longer than 6 h. Relatively
      high concentration of AYR accumulated at higher AYR loading rates (>780 gm(-3) d(
      1)) likely inhibited acetate oxidation of anode-respiring bacteria on the anode,
      which decreased current density in the UBER; optimal AYR loading rate for the
      UBER was 680 gm(-3) d(-1) (HRT 2.5 h). The subsequent ABOR further improved
      effluent quality. Overall the Chroma decreased from 320 times to 80 times in the
      combined bio-system to meet the textile wastewater discharge standard II in
      China.

PMID- 23009798
TI  - Electrochemical depassivation of zero-valent iron for trichloroethene reduction.
AB  - Permeable reactive barriers (PRBs) composed of zero-valent iron (ZVI) are
      susceptible to passivation, resulting in substantially decreased rates of
      chlorinated solvent removal over time. In this study, the application of low
      electrical direct current (DC) to restore the reductive capacity of passivated
      ZVI was examined. Electrical current was applied to a laboratory column reactor
      filled with a mixture of pre-passivated ZVI and sand. Variable voltage settings
      (0-12 V) were applied through two stainless steel electrodes placed at the ends
      of the reactor. While only partial restoration of the reductive capacity of the
      passivated ZVI was observed, higher rates of trichloroethene (TCE) removal were
      always obtained when current was applied, and the rates of TCE removal were
      roughly proportional to the voltage level. Although differences were observed
      between the rates and extent of TCE removal within the column, it is noteworthy
      that TCE removal was not restricted to that region of the column where the
      electrons entered (i.e., at the cathode). While complete "depassivation" of ZVI
      may be difficult to achieve in practice, the application of DC demonstrated
      observable restoration of reactivity of the passivated ZVI. This study provides
      evidence that this approach may significantly extend the life of a ZVI PRB.

PMID- 23009800
TI  - Computer simulation games as an adjunct for treatment in male veterans with
      alcohol use disorder.
AB  - This study examined the impact of a computer simulation designed to provide the
      opportunity for individuals with alcohol use disorders (AUDs) to practice relapse
      prevention skills. Participants were 41 male veterans enrolled in an intensive
      outpatient substance abuse treatment program. Participants were randomly assigned
      to either view educational slides about treatment for AUD or play a simulation
      videogame for eight sessions within 12 weeks. Participants were assessed at a 4
      week follow-up visit. Outcome measures included relapse rates as well as ratings
      on the Obsessive Compulsive Drinking Scale (OCDS) and a custom-designed relapse
      prevention self efficacy scale. While rates of relapse did not differ between
      groups, those who played the game showed overall reductions in ratings on the
      OCDS, as well as higher ratings of self-efficacy at week 8, suggesting that the
      videogame simulation may be a useful adjunct to AUD treatment.

PMID- 23009799
TI  - Regulation of Staphylococcus aureus immunodominant antigen B (IsaB).
AB  - Staphylococcus aureus is a leading cause of nosocomial and community-acquired
      infections and increased prevalence of antibiotic resistance has necessitated the
      search for novel therapeutic targets. The immunodominant antigen B induces an
      antibody response during septicemia and has therefore been proposed as a vaccine
      target. Because it appears to be expressed during infection but not during
      colonization, we sought to characterize the regulation of isaB expression by
      internal transcription factors and external stimuli. We found that expression of
      isaB was stimulated by glucose, human serum, and plasma. Furthermore isaB
      transcript levels increased in the absence of the global staphylococcal accessory
      regulator SarA and decreased in the absence of the carbon catabolite regulator
      CcpA. Interestingly, glucose and CcpA-mediated isaB expression appeared to be
      related to the decrease in pH subsequent to carbon metabolism, rather than a
      direct response to the carbon source and could be prevented by buffering the
      growth medium.

PMID- 23009801
TI  - Demographic screening for MRSA may compromise the effectiveness of ring fencing
      on a joint replacement unit.
AB  - Ring fencing of joint replacement (JR) units has been reported to reduce
      infections and is recommended by health authorities in Australia and the UK. It
      has not been determined whether a demographic risk assessment is adequate to
      prevent the admission of patients colonized with meticillin-resistant
      Staphylococcus aureus (MRSA) to ring-fenced units. As such, 250 admissions to the
      JR unit of a suburban Sydney hospital were screened, and MRSA colonization was
      identified in 2.8% of patients complying with the demographic risk assessment.
      Demographic risk assessment is not an adequate substitute for physical MRSA
      screening, and undermines the effectiveness of ring-fencing procedures.

PMID- 23009802
TI  - A simple inexpensive audio-visual reminder of infection control procedures on
      entry to a neonatal intensive care unit.
AB  - A novel audio-visual computerized infection control initiative was designed,
      installed and tested in the neonatal intensive care unit at a busy teaching
      hospital, with the primary aim of improving visitors' adherence to hand hygiene
      and infection control procedures. The system has proved to be reliable, self
      administering, inexpensive, requires no prior education or training, is rapidly
      deployable and can be used immediately. A measurable improvement in visitors'
      handwashing technique and recall of infection control instructions was seen after
      introduction of this initiative. This system provides a new opportunity to
      educate and promote infection control measures to visitors.

PMID- 23009803
TI  - Comparison of virucidal activity of alcohol-based hand sanitizers versus
      antimicrobial hand soaps in vitro and in vivo.
AB  - Three ethanol-based sanitizers were compared with three antimicrobial liquid
      soaps for their efficacy to inactivate polio-, adeno-, vaccinia- and bovine viral
      diarrhoea virus (BVDV) as well as feline calicivirus (FCV) and murine norovirus
      (MNV) as surrogates for human norovirus in a suspension test. Additionally,
      sanitizers and soaps were examined against MNV in a modified fingerpad method.
      All sanitizers sufficiently inactivated the test viruses in the suspension test
      whereas two soaps were active only against vaccinia virus and BVDV. In the
      modified fingerpad test a povidone-iodine-containing soap was superior to the
      sanitizers whereas the other two soaps showed no activity.

PMID- 23009804
TI  - Getting stuck in: protein palmitoylation in Plasmodium.
AB  - Palmitoylation is the reversible post-translational addition of a lipid moiety to
      cysteine residues on targeted proteins. The recent use of proteomic-scale
      techniques to study protein palmitoylation in multiple organisms has radically
      changed our understanding of the diversity of proteins and signaling pathways
      that are affected by palmitoylation. These experiments have made clear that,
      similarly to phosphorylation, palmitoylation is a regulatory tool that has an
      impact upon a wide range of essential eukaryotic processes. A recent proteome
      level analysis of protein palmitoylation in Plasmodium has revealed the
      importance of palmitoylation in parasite biology and has raised new and exciting
      questions about several Plasmodium-specific and virulence-associated processes.

PMID- 23009805
TI  - Public health benefits and risks of fish consumption: current scientific evidence
      v. media coverage.
AB  - OBJECTIVE: To evaluate if and how the current degree of scientific uncertainty
      about the safety of fish consumption is incorporated at the media level. DESIGN:
      We used a dedicated software (TalTac(r)) to investigate the content of 169 news
      articles related to 'mercury and fish consumption' that appeared from 1990 to
      2010 in the two Italian broadsheets with the highest circulation figures, in
      order to identify journalistic frames used in the coverage of benefits v. risks
      associated with fish consumption. Hypotheses were made on how the public might
      change fish consumption patterns as a result of media coverage. SETTING: Italy.
      RESULTS: The two newspapers have different agendas in covering the issue. La
      Repubblica appears to support the view that, besides health benefits, there may
      be risks associated with fish consumption, while Corriere della Sera emphasizes
      health benefits more than possible risks. Depending on the preferred information
      source, the public could: (i) reduce its fish intake; (ii) increase its fish
      intake; or (iii) become confused about the problem and sceptical towards the
      media, as a result of conflicting journalistic frames. CONCLUSIONS: The Italian
      media, in cooperation with scientists, public health nutritionists and
      dietitians, should place more emphasis on the existence of a few fish species
      with high to very high Hg levels and relatively low contents of beneficial n-3
      fatty acids (e.g. swordfish and shark). This would enable consumers to make more
      educated purchasing decisions to maximize the benefits of n-3 intake while
      reducing possible risks from consuming Hg-contaminated fish.

PMID- 23009806
TI  - Future prospects for salivary proteomics in rheumatology: the example of
      eosinophil granulomatosis with polyangiitis.

PMID- 23009807
TI  - Evaluation of structural features in fungal cytochromes P450 predicted to rule
      catalytic diversification.
AB  - Fungi belong to the large kingdom of lower eukaryotic organisms encompassing
      yeasts along with filamentous and dimorphic members. Microbial P450 enzymes have
      contributed to exploration of and adaptation to diverse ecological niches such as
      conversion of lipophilic compounds to more hydrophilic derivatives or degradation
      of a vast array of environmental toxicants. To better understand diversification
      of the catalytic behavior of fungal P450s, detailed insight into the molecular
      machinery steering oxidative attack on the distinctly structured endogenous and
      xenobiotic substrates is of preeminent interest. Based on a general, CYP102A1
      related template the bulk of predicted substrate/inhibitor-binding determinants
      were shown to cluster near the distal heme face within the six known substrate
      recognition sites (SRSs) made up by the alpha-helical B'/F/G/I tetrad, the B'-C
      interhelical loop and strands of the beta6-sheet, population density being
      highest in the structurally flexible SRS-1 and SRS-4 domains, showing a low
      degree of conservation. Reactivity toward ligands favorably coincides with the
      lipophilicity/hydrophilicity profile and bulkiness of critical amino acids acting
      as selective filters. Some decisive elements may also serve in maintenance of
      catalytic competence via their action as gatekeepers directing substrate
      access/positioning or stabilizers of the heme environment enabling dioxygen
      activation. Non-SRS residues seem to control spin state equilibria and attract
      redox partners by electrostatic forces. Of note, the inhibitory potency of azole
      type fungicides is likely to arise from perturbation of the complex interplay of
      the mechanistic principles addressed above. Knowledge-supported exploitation of
      the topological data will be helpful in the manufacture of commodity/specialty
      chemicals as well as therapeutic agents. Also, engineered fungal P450s may be
      used to improve pollutant-specific bioremediation of contaminated soils.

PMID- 23009808
TI  - The heterodimerization of platelet-derived chemokines.
AB  - Chemokines encompass a large family of proteins that act as chemoattractants and
      are involved in many biological processes. In particular, chemokines guide the
      migration of leukocytes during normal and inflammatory conditions. Recent studies
      reveal that the heterophilic interactions between chemokines significantly affect
      their biological activity, possibly representing a novel regulatory mechanism of
      the chemokine activities. The co-localization of platelet-derived chemokines in
      vivo allows them to interact. Here, we used nano-spray ionization mass
      spectrometry to screen eleven different CXC and CC platelet-derived chemokines
      for possible interactions with the two most abundant chemokines present in
      platelets, CXCL4 and CXCL7. Results indicate that many screened chemokines,
      although not all of them, form heterodimers with CXCL4 and/or CXCL7. In
      particular, a strong heterodimerization was observed between CXCL12 and CXCL4 or
      CXCL7. Compared to other chemokines, the main structural difference of CXCL12 is
      in the orientation and packing of the C-terminal alpha-helix in relation to the
      beta-sheet. The analysis of one possible structure of the CXCL4/CXCL12
      heterodimer, CXC-type structure, using molecular dynamics (MD) trajectory reveals
      that CXCL4 may undergo a conformational transition to alter the alpha helix
      orientation. In this new orientation, the alpha-helix of CXCL4 aligns in parallel
      with the CXCL12 alpha-helix, an energetically more favorable conformation.
      Further, we determined that CXCL4 and CXCL12 physically interact to form
      heterodimers by co-immunoprecipitations from human platelets. Overall, our
      results highlight that many platelet-derived chemokines are capable of
      heterophilic interactions and strongly support future studies of the biological
      impact of these interactions.

PMID- 23009809
TI  - Stereochemical features of the envelope protein Domain III of dengue virus
      reveals putative antigenic site in the five-fold symmetry axis.
AB  - We bring to attention a characteristic parasitic pattern present in the dengue
      virus: it undergoes several intensive thermodynamic variations due to host
      environmental changes, from a vector's digestive tract, through the human
      bloodstream and intracellular medium. Comparatively, among the known dengue
      serotypes, we evaluate the effects that these medium variations may induce to the
      overall structural characteristics of the Domain III of the envelope (E) protein,
      checking for stereochemical congruences that could lead to the identification of
      immunologic relevant regions. We used molecular dynamics and principal component
      analysis to study the protein in solution, for all four dengue serotypes, under
      distinct pH and temperature. We stated that, while the core of Domain III is
      remarkably rigid and effectively unaffected by most of the mentioned intensive
      variations, the loops account for major and distinguishable flexibilities.
      Therefore, the rigidity of the Domain III core provides a foothold that projects
      specifically two of these high flexible loop regions towards the inner face of
      the envelope pores, which are found at every five-fold symmetry axis of the
      icosahedron-shaped mature virus. These loops bear a remarkable low identity
      though with high occurrence of ionizable residues, including histidines. Such
      stereochemical properties can provide very particular serotype-specific
      electrostatic surface patterns, suggesting a viral fingerprint region, on which
      other specific molecules and ions can establish chemical interactions in an
      induced fit mechanism. We assert that the proposed regions share enough relevant
      features to qualify for further immunologic and pharmacologic essays, such as
      target peptide synthesis and phage display using dengue patients' sera.

PMID- 23009810
TI  - Translational control by negative-strand RNA viruses: methods for the study of a
      crucial virus/host interaction.
AB  - Protein synthesis is a vital step in the successful replication of negative
      strand RNA viruses. Protein synthesis is also a critical step in the development
      of a successful antiviral response from the host. This makes understanding the
      interplay between host and viral translation an important aspect of defining the
      virus/host interaction. For the negative-strand RNA viruses there are disparate
      mechanism of how viruses interact with the host protein synthesis apparatus,
      ranging from the complete takeover of all protein synthesis to the subtle
      insertion of viral mRNAs into an otherwise unchanged protein synthesis pattern.
      In this article, we discuss different ways to investigate protein synthesis in
      virus-infected cells, ranging from the use of metabolic labeling for the study of
      general translation changes to using fluorescence-coupled labeling techniques
      that allow the pinpointing of any subcellular localization of protein synthesis
      during virus replication. We also discuss methods for analyzing the translation
      initiation factors that are frequently modified in virus-infected cells.

PMID- 23009811
TI  - Methods for studying IRES-mediated translation of positive-strand RNA viruses.
AB  - Internal ribosome entry sites are RNA elements that mediate translation in a cap
      independent manner. A subset of positive strand RNA viruses utilize an IRES
      mechanism as a viral strategy to ensure efficient viral protein synthesis. IRES
      elements vary in sequence, structure, and factor requirements between virus
      families. Here, we describe methods to determine IRES activity and approaches to
      study the regulation and function of IRES-mediated translation both in vitro and
      in vivo. Finally, we describe a new IRES-directed reporter system which exploits
      the 2A 'self-cleavage' or 'stop-go' peptide for optimal detection of IRES
      activity.

PMID- 23009812
TI  - Entry and replication of recombinant hepatitis C viruses in cell culture.
AB  - Hepatitis C virus (HCV) is a positive-strand enveloped RNA virus and belongs to
      the Flaviviridae family. The heavy health burden associated with the virus
      infection in humans and the intriguing peculiarities of the interaction between
      the HCV replication cycle and the hepatocyte host cell have stimulated a
      flourishing research field. The present review aims at recapitulating the
      different viral and cellular systems modelling HCV entry and replication, and in
      particular at gathering the tools available to dissect the HCV entry pathway.

PMID- 23009813
TI  - Role of membrane addition in animal cell cytokinesis.
AB  - Addition of membrane in the form of vesicles is essential for the cytokinesis of
      animal and plant cells. In the animal cell cytokinesis, membrane fusion acts
      along with the contraction of an actomyosin ring to separate the cytoplasmic
      contents. In this study, the possible driving mechanisms for the membrane
      addition to the plasma membrane of the dividing animal cell and their
      consequences are presented. Taking cues from earlier studies, we propose that the
      membrane addition to the plasma membrane in the form of vesicles can be governed
      by the lateral tension present in the plasma membrane or, the concentrations of
      actin and myosin proteins at the cleavage furrow or, both simultaneously. The
      study attempts to elucidate the relationship between membrane addition and the
      force exerted by the contractile ring. The predictions from our study agree
      qualitatively with the experimental studies in which the vesicle fusion or the
      acto-myosin assembly were blocked during cytokinesis. However, the precise role
      of the two above mentioned mechanisms may depend on various parameters including
      but not limited to the cell type, organism and microenvironment around the
      dividing cell.

PMID- 23009814
TI  - Metal accumulation in fish from different zones of a large, shallow freshwater
      lake.
AB  - Metal (Cd, Pb, Cr, Ni, Mn, Cu, and Zn) concentrations in different fish species
      sampled from two distinct (phytoplankton- and macrophyte-dominated) lake zones of
      a large, shallow freshwater lake, Taihu Lake, were investigated. Concentrations
      of most metals in muscle of the small-sized fish (Protosalanx hyalocranius,
      Pseudorasbora parva, and Rhodeus ocellatus) were always significantly higher than
      those of the large-sized (Carassius auratus, Cyprinus carpio, and Aristichthys
      nobilis) and carnivorous fish (Pelteobagrus fulvidraco, Cultrichthys
      erythropterus, and Erythroculter ilishaeformis). Metal accumulation in the small
      sized fish from the phytoplankton-dominated lake zone was always greater than
      those from the macrophyte-dominated lake zone in summer. However, no significant
      differences were observed between the two lake zones for most metals in the small
      sized fish collected in winter. Metal accumulation in gills, liver, and intestine
      of the large-sized fish from the phytoplankton-dominated lake zone was generally
      greater than those from the macrophyte-dominated lake zone in summer. The
      presence of distinct ecological regions in the lake might affect the metal
      distribution in the small-sized or large-sized fish. For the carnivorous fish,
      however, metal concentrations in fish tissues from the two different lake zones
      were not significantly different, suggesting that metal accumulation in
      carnivorous fish might be less influenced by the ecological status of the lake.

PMID- 23009815
TI  - Response of antioxidant defences to Zn stress in three duckweed species.
AB  - In the plants, Lemna gibba, Lemna minor and Spirodela polyrrhiza L., the effect
      of different concentrations of zinc (0.01, 0.05, 0.1, 0.5 and 1.5mgL(-1) Zn)
      applied for four day was assessed by measuring changes in the chlorophyll,
      protein, malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD),
      ascorbate peroxidase (APX) and guiacolperoxidase (GPX) activity of the plants.
      According to results, Zn contents in plants increased with increasing Zn supply
      levels. The level of photosynthetic pigments and soluble proteins reduced only
      upon exposure to high Zn concentrations. At the same time, the level of
      malondialdehyde (MDA) increased with increasing Zn concentration. These results
      suggested an alleviation of stress that was possibly the result of antioxidants
      such as catalase (CAT), superoxide dismutase (SOD), ascorbate peroxidase (APX) as
      well as guaiacol peroxidise (GPOX), which increased linearly with increasing Zn
      levels. Cellular antioxidant levels showed an increase suggesting a defensive
      mechanism to preserve against oxidative stress given rise to by Zn. Besides, the
      proline amount in L. gibba, L. minor and S. polyrrhiza increased with increasing
      zinc levels. These conclusions proposed that L. gibba, L. minor and S. polyrrhiza
      are supplied with an efficient antioxidant mechanism against Zn-induced oxidative
      stress which saves the plant's photosynthetic machinery from damage. It is
      concluded that higher zinc levels cause oxidative stress in L. gibba, L. minor
      and S. polyrrhiza cells and may reason membrane damage through production of ROS
      and interferes with chlorophyll metabolism.

PMID- 23009816
TI  - [A man with a painful knee].
AB  - A 53-year-old patient presented with a rupture of the left patellar tendon. The
      tendon was reconstructed using Krackow whipstitch sutures through drill holes in
      the patella.

PMID- 23009817
TI  - [A man with progressive neck and shoulder pain].
AB  - A 66-year-old man was referred to the hospital with progressive neck and right
      shoulder pain. Conventional radiographs and a thoracic CT-scan demonstrated
      destruction of the first rib on the right side due to a tumour invading the
      apical chest wall. The patient was diagnosed with a Pancoast tumour (i.e.
      superior sulcus tumour).

PMID- 23009818
TI  - [A man with a painful thumb].
AB  - A 22-year-old man presented with a subluxation of the metacarpophalangeal joint
      of his left thumb. Correct anatomical position was obtained with manual
      reposition. The hand was immobilised for 2 weeks and was thereafter actively
      mobilised. After 1 month he was free of pain and the function of his thumb had
      completely recovered.

PMID- 23009819
TI  - [A woman with a perianal skin disease].
AB  - A 69-year-old woman presented with a large pigmented perianal ulcer and inguinal
      lymphomas. The ulcer was fixed to the rectovaginal septum and the anal sphincter.
      Histological examination of a perianal skin biopsy revealed an anorectal
      melanoma. Prognosis is poor in these patients, median survival being less than 20
      months.

PMID- 23009820
TI  - [A newborn with an ovarian cyst].
AB  - BACKGROUND: An ovarian cyst is one of the most common types of cysts found in
      neonates. As a result of the introduction of the 20-week screening ultrasound,
      the detection of ovarian cysts will likely increase. CASE DESCRIPTION: An
      abdominal cyst was detected by ultrasound in a female foetus in her 20th
      gestational week. This simple cyst remained smaller than 5 cm in diameter so an
      expectative course was opted for. Six months after her birth, however, the cyst's
      echographic appearance changed. A necrotic left ovary was resected during a
      diagnostic laparoscopy. CONCLUSION: We recommend taking an expectative approach
      to asymptomatic simple or complex ovarian cysts, because they usually regress
      spontaneously in the first year of life. It is important to monitor the cyst by
      ultrasound and to repeatedly measure tumour marker concentrations as necessary.

PMID- 23009821
TI  - [Post-traumatic lung herniation].
AB  - BACKGROUND: Post-traumatic lung herniation due to a pathological defect in the
      chest wall is rare. CASE DESCRIPTION: We present a 73-year-old polytrauma patient
      who had extensive chest wall trauma after an accident, resulting in traumatic
      herniation of the lung. The patient was initially treated according to surgical
      principles for 'damage control'. The chest wall was then reconstructed with
      polypropylene mesh. CONCLUSION: There is still no consensus on surgical treatment
      of lung herniation. It may be performed immediately (primary) or after a delay
      (secondary) and depends on the clinical condition of the patient.

PMID- 23009822
TI  - [Double-balloon enteroscopy in children: indications, safety, and efficacy].
AB  - BACKGROUND: Double-balloon enteroscopy is a technique that utilises an endoscope
      equipped with an overtube to inspect the entire small bowel. Diagnostic and
      therapeutic procedures can be performed during this type of endoscopy. So far,
      the use of this technique in children has been limited. In this article, we
      present a case illustrating the indication, efficacy and safety of this technique
      in the paediatric setting. CASE DESCRIPTION: In a 17-year-old girl with chronic
      abdominal pain and iron deficiency anaemia, neither gastroduodenoscopy nor
      ileocolonoscopy revealed any abnormality. Video capsule endoscopy revealed a few
      suspicious erosive lesions and ulcerations, presumed to be located in the ileum.
      A double-balloon enteroscopy was then performed during which an ulcer was seen on
      a small-bowel stenosis; this was consistent with the diagnosis of Crohn's
      disease. The symptoms diminished after treatment with budesonide and azathioprine
      was initiated. CONCLUSION: Double-balloon enteroscopy also appears to be an
      effective and safe method of diagnosing and performing therapeutic interventions
      in paediatric small bowel pathology.

PMID- 23009823
TI  - [Quincke and his oedema].
AB  - Heinrich Irenaeus Quincke (1842-1922), the son of a physician, was born in
      Frankfurt but was educated in Berlin where he also completed his medical studies
      in 1864. After a 'grand tour' that took him to Paris, Vienna and London, he was
      trained in Berlin, first in surgery and later in internal medicine, under Von
      Frerichs (1819-1885). In 1878, he became a professor of internal medicine in
      Berne; from 1883 he held the chair of medicine in Kiel, which he would hold for
      the next 30 years. In 1882, he published a synthesis of several observations of
      'acute, circumscribed oedema of the skin'. Quincke accurately described the
      clinical features and distinguished the familial from the sporadic forms. He was
      correct in attributing the condition to increased vascular permeability, but he
      surmised the causal factors were neurogenic rather than humoral, according to
      current insights (excess of bradykinin due to external factors or hereditary
      deficiency of C1-esterase inhibitor). Quincke not only contributed to several
      other clinical observations, but also pioneered the lumbar puncture, initially
      not for diagnostic purposes, but to relieve headache in hydrocephalic children.

PMID- 23009824
TI  - [New oral anticoagulants for atrial fibrillation: a neurologist's view].
AB  - Recent randomized controlled trials have shown that new oral anticoagulants
      (dabigatran, rivaroxaban en apixaban) in patients with atrial fibrillation are
      equally or more effective in preventing cerebral infarction than vitamin K
      antagonists (VKA). New oral anticoagulants cause significant less intracranial
      haemorrhages. These results also apply to patients at high risk for complications
      such as those with a history of cerebral infarction, and those aged 75 years and
      over. It is not known whether patients in the acute phase after cerebral
      infarction and those with blood pressure exceeding 180/110 mmHg benefit as well.
      Monitoring anticoagulation is no longer needed in patients using these new oral
      anticoagulants, which makes daily use easier but provides less insight into
      medication compliance. There is no need to switch medication in patients who
      respond well to VKA. However, new oral anticoagulants should be considered in
      patients who have problems with VKA and who have a de novo indication for
      anticoagulation. Practical issues such as interaction with other drugs,
      medication compliance, antagonizing, monitoring of the anticoagulation and
      asymptomatic deteriorating renal function should be studied further.

PMID- 23009826
TI  - [How the media get the blame for everything].
AB  - Scientists, just like everyone else, have to be careful and meticulous in their
      contact with the media. Journalists do not get it all right all the time, but it
      is too easy to try to blame them if things do not go as expected.

PMID- 23009827
TI  - Effect of cigarette smoking on human oviductal ciliation and ciliogenesis.
AB  - OBJECTIVE: To investigate the effect of cigarette smoke exposure on ciliation and
      ciliogenesis in human oviductal epithelium. DESIGN: Molecular analysis using
      human tubal segments. SETTING: Academic medical center. PATIENT(S): Twenty women
      undergoing elective tubal sterilization procedure. INTERVENTION(S): Expression of
      ciliated cell-specific markers was compared in tubal segments from smokers and
      nonsmokers using quantitative immunohistochemistry and Western blot analysis. The
      expression of transcription factors in the motile ciliogenesis program was
      compared using quantitative polymerase chain reaction and quantitative
      immunohistochemistry. MAIN OUTCOME MEASURE(S): Oviductal ciliation and expression
      of transcription factors involved in ciliogenesis. RESULT(S): No significant
      differences were detected in density of ciliation between groups. Neither number
      of years of smoking nor pack-year history correlated with density of ciliation.
      Expression of ciliogenic transcription factors FOXJ1, RFX2, and RFX3 was
      consistent between groups. CONCLUSION(S): Few studies have evaluated the
      relationship between smoking and ciliated epithelium in human oviducts. Cigarette
      smoking does not seem to result in quantitative differences in the density of
      ciliation nor expression of ciliogenesis factors. Our findings suggest that
      pathophysiologic mechanisms other than ciliation account for the increased risk
      of ectopic pregnancy in women who smoke.

PMID- 23009828
TI  - Breast Cancer Incidence After Risk-Reducing Salpingo-Oophorectomy in BRCA1 and
      BRCA2 Mutation Carriers.
AB  - Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation
      carriers effectively reduces ovarian cancer risk, but also reduces breast cancer
      risk. Breast cancer risk reductions up to 50% have been reported for both BRCA1
      and BRCA2 mutation carriers, but recent prospective studies were not able to
      reproduce this finding for BRCA1 mutation carriers. Breast cancer incidence after
      RRSO was assessed in a consecutive series of 104 BRCA1 and 58 BRCA2 mutation
      carriers. On the basis of data from our own centre, and assuming a 50% risk
      reduction through RRSO at premenopausal age, we expected to find 8 breast cancers
      (range 6-10) in this population for the reported screening period (532 women
      years). In 162 carriers with a median age of 41 years at RRSO, 13 incident breast
      cancers were diagnosed. In BRCA1 mutation carriers, 12 incident breast cancers
      were found compared with 5 (range 3-6) expected and in BRCA2 mutation carriers 1
      breast cancer was found compared with 3 (range 2-5) expected. Breast cancer
      incidence after premenopausal RRSO is still high, especially in BRCA1 mutation
      carriers. Previously reported breast cancer risk reductions up to 50% were not
      confirmed. As a consequence, continued intensive screening for breast cancer is
      warranted in BRCA1 and BRCA2 mutation carriers after RRSO.

PMID- 23009829
TI  - Transition-metal-free oxyarylation of alkenes with aryl diazonium salts and
      TEMPONa.
AB  - The reaction of readily available TEMPONa with aryl diazonium salts allows for
      clean generation of the corresponding aryl radicals along with TEMPO. Aryl
      radical addition to alkenes with subsequent TEMPO trapping provides the
      corresponding oxyarylation products in good to excellent yields. These
      experimentally easy to conduct transformations occur in the absence of any
      transition metal under mild conditions, and the process shows broad functional
      group compatibility.

PMID- 23009831
TI  - Vascular injury and concomitant long-bone fracture in war wounds.

PMID- 23009832
TI  - Application of duplex ultrasound imaging in determining in-stent stenosis during
      surveillance after mesenteric artery revascularization.
AB  - OBJECTIVE: Currently, there are no well-established duplex ultrasound (DUS)
      criteria for the evaluation of the mesenteric arteries after stenting for
      occlusive disease. Previous studies suggested DUS velocity criteria in the native
      superior mesenteric artery (SMA) overestimate stenosis in stented arteries, but
      most studies have not evaluated DUS imaging after SMA stenting longitudinally.
      This study was undertaken to determine the accuracy of DUS after mesenteric
      artery revascularization and, in particular, to evaluate the utility of DUS
      imaging for the detection of in-stent stenosis (ISS) of the SMA. METHODS: A
      retrospective record review was performed for all patients who underwent SMA
      stenting for chronic mesenteric ischemia at a single institution from January
      2004 to May 2011. RESULTS: Mesenteric artery occlusive disease resulted in 24
      patients undergoing mesenteric stenting of the SMA alone (n = 20) or the SMA and
      celiac artery simultaneously (n = 3). The mean +/- standard deviation peak
      systolic velocity (PSV) in 13 prestent DUS images of the SMA was 464 +/- 130
      cm/s. Prestenting angiography revealed an average SMA stenosis of 79% +/- 14%.
      After stenting, completion angiography in each case revealed <20% residual
      stenosis. No significant correlation was identified between SMA PSV and
      angiographic stenosis before and after stenting (P > .05). Follow-up SMA DUS
      imaging showed an average PSV of 335 +/- 138 cm/s at 0.9 +/- 1.5 months, 360 +/-
      143 cm/s at 4.8 +/-2.6 months, and 389 +/- 95 cm/s at 14.4 +/- 5.1 months. A
      significant difference existed between the prestent and the first poststent mean
      SMA PSV (P < .05), but no significant difference existed between each
      poststenting interval. Eight reinterventions for SMA ISS were performed, with a
      mean elevated in-stent SMA PSV of 505 +/- 74 vs 341 +/- 145 cm/s in patients who
      did not undergo reintervention. Angiography before the eight reinterventions
      demonstrated an average SMA ISS of 53% +/- 25%. In-stent SMA PSV decreased from
      505 +/- 74 to 398 +/- 108 cm/s after the reintervention (P < .05). CONCLUSIONS:
      Consistent with other reports, our data demonstrate the PSV in successfully
      stented SMAs remains higher than the PSV threshold of 275 cm/s used for the
      diagnosis of high-grade native SMA stenosis. In addition, in-stent SMA PSVs did
      not significantly change over DUS surveillance for patients who did not undergo
      reintervention. Thus, obtaining a baseline DUS early after mesenteric stenting
      should be considered to compare future surveillance DUS. An increase above this
      baseline or an in-stent SMA PSV approaching 500 cm/s should be considered
      suspicious for ISS, but larger prospective studies will be required to validate
      these preliminary findings.

PMID- 23009833
TI  - Tuning the calcium sensitivity of cardiac muscle.

PMID- 23009834
TI  - Dynamic organization of transcription compartments is dependent on functional
      nuclear architecture.
AB  - Transcription in higher organisms requires spatiotemporal coordination of
      transcription machinery and the transcription factors at promoter sites. Toward
      this, recent evidence suggests that both static compartmentalization and dynamic
      self-organization of transcriptional apparatus are in effect at sites of
      transcription. Although the dynamics of transcription machinery is essential to
      genome regulation, the principles underlying this organization and its functional
      coupling to nuclear architecture is unclear. In a recent study we revealed that
      Uridine-5'-triphosphate (UTP) uptake in living cells labeled transcription
      related compartments. In this article, we quantitatively establish multicolor
      labeling strategies for UTP-enriched transcription compartments (TCs) and probe
      their dynamic organization. UTP-enriched TCs were found to be in two distinct
      fractions: one colocalized with phosphorylated RNA pol II and the other as
      nascent aggregates. The fraction colocalized with the phosphorylated RNA pol II
      decreased with the inhibition of transcription initiation or elongation.
      Fluorescence anisotropy imaging and photobleaching experiments suggest that TCs
      are functional aggregates of nascent transcripts that are assembled in a
      transcription-dependent manner. Fluorescence correlation spectroscopy analysis
      revealed the relative fraction and sizes of fluorescent UTP-labeled transcripts
      in the nucleoplasm. Time-lapse imaging experiments of TCs exhibited pause and a
      mobile nature of these compartments within interchromosome territories.
      Perturbation of either nucleoskeletal protein or the cytoskeleton resulted in
      reduced active mobility of TCs, whereas inhibitors of transcription enhanced the
      mobile fraction of TCs. Further, high temporal resolution imaging showed evidence
      of stepping dynamics of TCs regulated by nucleoskeleton and chromatin
      modifications. Taken together, our experiments suggest the transient
      compartmentalization of UTP-enriched aggregates and their dynamic reorganization
      in a transcription-dependent manner. These results may have important
      implications for understanding spatiotemporal control of eukaryotic
      transcription.

PMID- 23009835
TI  - Maximal force characteristics of the Ca(2+)-powered actuator of Vorticella
      convallaria.
AB  - The millisecond stalk contraction of the sessile ciliate Vorticella convallaria
      is powered by energy from Ca(2+) binding to generate contractile forces of ~10
      nN. Its contractile organelle, the spasmoneme, generates higher contractile force
      under increased stall resistances. By applying viscous drag force to contracting
      V. convallaria in a microfluidic channel, we observed that the mechanical force
      and work of the spasmoneme depended on the stalk length, i.e., the maximum
      tension (150-350 nN) and work linearly depended on the stalk length (~2.5 nN and
      ~30 fJ per 1 MUm of the stalk). This stalk-length dependency suggests that motor
      units of the spasmoneme may be organized in such a way that the mechanical force
      and work of each unit cumulate in series along the spasmoneme.

PMID- 23009836
TI  - Elasticity maps of living neurons measured by combined fluorescence and atomic
      force microscopy.
AB  - Detailed knowledge of mechanical parameters such as cell elasticity, stiffness of
      the growth substrate, or traction stresses generated during axonal extensions is
      essential for understanding the mechanisms that control neuronal growth. Here, we
      combine atomic force microscopy-based force spectroscopy with fluorescence
      microscopy to produce systematic, high-resolution elasticity maps for three
      different types of live neuronal cells: cortical (embryonic rat), embryonic chick
      dorsal root ganglion, and P-19 (mouse embryonic carcinoma stem cells) neurons. We
      measure how the stiffness of neurons changes both during neurite outgrowth and
      upon disruption of microtubules of the cell. We find reversible local stiffening
      of the cell during growth, and show that the increase in local elastic modulus is
      primarily due to the formation of microtubules. We also report that cortical and
      P-19 neurons have similar elasticity maps, with elastic moduli in the range 0.1-2
      kPa, with typical average values of 0.4 kPa (P-19) and 0.2 kPa (cortical). In
      contrast, dorsal root ganglion neurons are stiffer than P-19 and cortical cells,
      yielding elastic moduli in the range 0.1-8 kPa, with typical average values of
      0.9 kPa. Finally, we report no measurable influence of substrate protein coating
      on cell body elasticity for the three types of neurons.

PMID- 23009837
TI  - Ion-controlled conformational dynamics in the outward-open transition from an
      occluded state of LeuT.
AB  - Neurotransmitter:sodium symporter (NSS) proteins are secondary Na(+)-driven
      active transporters that terminate neurotransmission by substrate uptake. Despite
      the availability of high-resolution crystal structures of a bacterial homolog of
      NSSs-Leucine Transporter (LeuT)-and extensive computational and experimental
      structure-function studies, unanswered questions remain regarding the transport
      mechanisms. We used microsecond atomistic molecular-dynamics (MD) simulations and
      free-energy computations to reveal ion-controlled conformational dynamics of LeuT
      in relation to binding affinity and selectivity of the more extracellularly
      positioned Na(+) binding site (Na1 site). In the course of MD simulations
      starting from the occluded state with bound Na(+), but in the absence of
      substrate, we find a spontaneous transition of the extracellular vestibule of
      LeuT into an outward-open conformation. The outward opening is enhanced by the
      absence of Na1 and modulated by the protonation state of the Na1-associated Glu
      290. Consistently, the Na(+) affinity for the Na1 site is inversely correlated
      with the extent of outward-open character and is lower than in the occluded state
      with bound substrate; however, the Na1 site retains its selectivity for Na(+)
      over K(+) in such conformational transitions. To the best of our knowledge, our
      findings shed new light on the Na(+)-driven transport cycle and on the symmetry
      in structural rearrangements for outward- and inward-open transitions.

PMID- 23009838
TI  - On the Lubensky-Nelson model of polymer translocation through nanopores.
AB  - We revisit the one-dimensional stochastic model of an earlier study by D. K.
      Lubensky and D. R. Nelson for the electrically driven translocation of
      polynucleotides through alpha-hemolysin pores. We show that the model correctly
      describes two further important properties of the experimentally observed
      translocation time distributions, namely their spread (width) and their
      exponential decay. The resulting overall agreement between theoretical and
      experimental translocation time distributions is thus very good.

PMID- 23009839
TI  - Confidence intervals for concentration and brightness from fluorescence
      fluctuation measurements.
AB  - The theory of photon count histogram (PCH) analysis describes the distribution of
      fluorescence fluctuation amplitudes due to populations of fluorophores diffusing
      through a focused laser beam and provides a rigorous framework through which the
      brightnesses and concentrations of the fluorophores can be determined. In
      practice, however, the brightnesses and concentrations of only a few components
      can be identified. Brightnesses and concentrations are determined by a nonlinear
      least-squares fit of a theoretical model to the experimental PCH derived from a
      record of fluorescence intensity fluctuations. The chi(2) hypersurface in the
      neighborhood of the optimum parameter set can have varying degrees of curvature,
      due to the intrinsic curvature of the model, the specific parameter values of the
      system under study, and the relative noise in the data. Because of this varying
      curvature, parameters estimated from the least-squares analysis have varying
      degrees of uncertainty associated with them. There are several methods for
      assigning confidence intervals to the parameters, but these methods have
      different efficacies for PCH data. Here, we evaluate several approaches to
      confidence interval estimation for PCH data, including asymptotic standard error,
      likelihood joint-confidence region, likelihood confidence intervals, skew
      corrected and accelerated bootstrap (BCa), and Monte Carlo residual resampling
      methods. We study these with a model two-dimensional membrane system for
      simplicity, but the principles are applicable as well to fluorophores diffusing
      in three-dimensional solution. Using simulated fluorescence fluctuation data, we
      find the BCa method to be particularly well-suited for estimating confidence
      intervals in PCH analysis, and several other methods to be less so. Using the BCa
      method and additional simulated fluctuation data, we find that confidence
      intervals can be reduced dramatically for a specific non-Gaussian beam profile.

PMID- 23009840
TI  - Probing the orientational distribution of dyes in membranes through multiphoton
      microscopy.
AB  - Numerous dyes are available or under development for probing the structural and
      functional properties of biological membranes. Exogenous chromophores adopt a
      range of orientations when bound to membranes, which have a drastic effect on
      their biophysical behavior. Here, we present a method that employs optical
      anisotropy data from three polarization-imaging techniques to establish the
      distribution of orientations adopted by molecules in monolayers and bilayers. The
      resulting probability density functions, which contain the preferred molecular
      tilt MU and distribution breadth gamma, are more informative than an average tilt
      angle [phi]. We describe a methodology for the extraction of anisotropy data
      through an image-processing technology that decreases the error in polarization
      measurements by about a factor of four. We use this technique to compare di-4
      ANEPPS and di-8-ANEPPS, both dipolar dyes, using data from polarized 1-photon, 2
      photon fluorescence and second-harmonic generation imaging. We find that di-8
      ANEPPS has a lower tilt but the same distributional width. We find the
      distribution of tilts taken by di-4-ANEPPS in two phospholipid membrane models:
      giant unilamellar vesicles and water-in-oil droplet monolayers. Both models
      result in similar distribution functions with average tilts of 52 degrees  and 47
      degrees , respectively.

PMID- 23009841
TI  - The capacitance and electromechanical coupling of lipid membranes close to
      transitions: the effect of electrostriction.
AB  - Biomembranes are thin capacitors with the unique feature of displaying phase
      transitions in a physiologically relevant regime. We investigate the voltage and
      lateral pressure dependence of their capacitance close to their chain melting
      transition. Because the gel and the fluid membrane have different area and
      thickness, the capacitance of the two membrane phases is different. In the
      presence of external fields, charges exert forces that can influence the state of
      the membrane, thereby influencing the transition temperature. This phenomenon is
      called "electrostriction". We show that this effect allows us to introduce a
      capacitive susceptibility that assumes a maximum in the melting transition with
      an associated excess charge. As a consequence, voltage regimes exist in which a
      small change in voltage can lead to a large uptake of charge and a large
      capacitive current. Furthermore, we consider electromechanical behavior such as
      pressure-induced changes in capacitance, and the application of such concepts in
      biology.

PMID- 23009842
TI  - Structural states and dynamics of the D-loop in actin.
AB  - Conformational changes induced by ATP hydrolysis on actin are involved in the
      regulation of complex actin networks. Previous structural and biochemical data
      implicate the DNase I binding loop (D-loop) of actin in such nucleotide-dependent
      changes. Here, we investigated the structural and conformational states of the D
      loop (in solution) using cysteine scanning mutagenesis and site-directed
      labeling. The reactivity of D-loop cysteine mutants toward acrylodan and the
      mobility of spin labels on these mutants do not show patterns of an alpha-helical
      structure in monomeric and filamentous actin, irrespective of the bound
      nucleotide. Upon transition from monomeric to filamentous actin, acrylodan
      emission spectra and electron paramagnetic resonance line shapes of labeled
      mutants are blue-shifted and more immobilized, respectively, with the central
      residues (residues 43-47) showing the most drastic changes. Moreover, complex
      electron paramagnetic resonance line shapes of spin-labeled mutants suggest
      several conformational states of the D-loop. Together with a new (to our
      knowledge) actin crystal structure that reveals the D-loop in a unique hairpin
      conformation, our data suggest that the D-loop equilibrates in F-actin among
      different conformational states irrespective of the nucleotide state of actin.

PMID- 23009843
TI  - The N-terminal extension of cardiac troponin T stabilizes the blocked state of
      cardiac thin filament.
AB  - Cardiac troponin T (cTnT) is a key component of contractile regulatory proteins.
      cTnT is characterized by a ~32 amino acid N-terminal extension (NTE), the
      function of which remains unknown. To understand its function, we generated a
      transgenic (TG) mouse line that expressed a recombinant chimeric cTnT in which
      the NTE of mouse cTnT was removed by replacing its 1-73 residues with the
      corresponding 1-41 residues of mouse fast skeletal TnT. Detergent-skinned
      papillary muscle fibers from non-TG (NTG) and TG mouse hearts were used to
      measure tension, ATPase activity, Ca(2+) sensitivity (pCa(50)) of tension, rate
      of tension redevelopment, dynamic muscle fiber stiffness, and maximal fiber
      shortening velocity at sarcomere lengths (SLs) of 1.9 and 2.3 MUm. Ca(2+)
      sensitivity increased significantly in TG fibers at both short SL (pCa(50) of
      5.96 vs. 5.62 in NTG fibers) and long SL (pCa(50) of 6.10 vs. 5.76 in NTG
      fibers). Maximal cross-bridge turnover and detachment kinetics were unaltered in
      TG fibers. Our data suggest that the NTE constrains cardiac thin filament
      activation such that the transition of the thin filament from the blocked to the
      closed state becomes less responsive to Ca(2+). Our finding has implications
      regarding the effect of tissue- and disease-related changes in cTnT isoforms on
      cardiac muscle function.

PMID- 23009844
TI  - Protein oligomerization monitored by fluorescence fluctuation spectroscopy: self
      assembly of rubisco activase.
AB  - A methodology is presented to characterize complex protein assembly pathways by
      fluorescence correlation spectroscopy. We have derived the total autocorrelation
      function describing the behavior of mixtures of labeled and unlabeled protein
      under equilibrium conditions. Our modeling approach allows us to quantitatively
      consider the relevance of any proposed intermediate form, and K(d) values can be
      estimated even when several oligomeric species coexist. We have tested this
      method on the AAA+ ATPase Rubisco activase (Rca). Rca self-association regulates
      the CO(2) fixing activity of the enzyme Rubisco, directly affecting biomass
      accumulation in higher plants. However, the elucidation of its assembly pathway
      has remained challenging, precluding a detailed mechanistic investigation. Here,
      we present the first, to our knowledge, thermodynamic characterization of
      oligomeric states of cotton beta-Rca complexed with Mg.ADP. We find that the
      monomer is the dominating species below 0.5 micromolar. The most plausible model
      supports dissociation constants of ~4, 1, and 1 micromolar for the monomer-dimer,
      dimer-tetramer, and tetramer-hexamer equilibria, in line with the coexistence of
      four different oligomeric forms under typical assay conditions. Large aggregates
      become dominant above 40 micromolar, with continued assembly at even higher
      concentrations. We propose that under some conditions, ADP-bound Rca self
      associates by forming spiral arrangements that grow along the helical axis. Other
      models such as the stacking of closed hexameric rings are also discussed.

PMID- 23009845
TI  - Coarse-grain simulations reveal movement of the synaptobrevin C-terminus in
      response to piconewton forces.
AB  - Fusion of neurosecretory vesicles with the plasma membrane is mediated by SNARE
      proteins, which transfer a force to the membranes. However, the mechanism by
      which this force transfer induces fusion pore formation is still unknown. The
      neuronal vesicular SNARE protein synaptobrevin 2 (syb2) is anchored in the
      vesicle membrane by a single C-terminal transmembrane (TM) helix. In coarse-grain
      molecular-dynamics simulations, self-assembly of the membrane occurred with the
      syb2 TM domain inserted, as expected from experimental data. The free-energy
      profile for the position of the syb2 membrane anchor in the membrane was
      determined using umbrella sampling. To predict the free-energy landscapes for a
      reaction pathway pulling syb2 toward the extravesicular side of the membrane,
      which is the direction of the force transfer from the SNARE complex, harmonic
      potentials were applied to the peptide in its unbiased position, pulling it
      toward new biased equilibrium positions. Application of piconewton forces to the
      extravesicular end of the TM helix in the simulation detached the synaptobrevin C
      terminus from the vesicle's inner-leaflet lipid headgroups and pulled it deeper
      into the membrane. This C-terminal movement was facilitated and hindered by
      specific mutations in parallel with experimentally observed facilitation and
      inhibition of fusion. Direct application of such forces to the intravesicular end
      of the TM domain resulted in tilting motion of the TM domain through the membrane
      with an activation energy of ~70 kJ/mol. The results suggest a mechanism whereby
      fusion pore formation is induced by movement of the charged syb2 C-terminus
      within the membrane in response to pulling and tilting forces generated by C
      terminal zippering of the SNARE complex.

PMID- 23009846
TI  - Role of the DELSEED loop in torque transmission of F1-ATPase.
AB  - F(1)-ATPase is an ATP-driven rotary motor that generates torque at the interface
      between the catalytic beta-subunits and the rotor gamma-subunit. The beta-subunit
      inwardly rotates the C-terminal domain upon nucleotide binding/dissociation;
      hence, the region of the C-terminal domain that is in direct contact with gamma
      termed the DELSEED loop-is thought to play a critical role in torque
      transmission. We substituted all the DELSEED loop residues with alanine to
      diminish specific DELSEED loop-gamma interactions and with glycine to disrupt the
      loop structure. All the mutants rotated unidirectionally with kinetic parameters
      comparable to those of the wild-type F(1), suggesting that the specific
      interactions between DELSEED loop and gamma is not involved in cooperative
      interplays between the catalytic beta-subunits. Glycine substitution mutants
      generated half the torque of the wild-type F(1), whereas the alanine mutant
      generated comparable torque. Fluctuation analyses of the glycine/alanine mutants
      revealed that the gamma-subunit was less tightly held in the alpha(3)beta(3)
      stator ring of the glycine mutant than in the wild-type F(1) and the alanine
      mutant. Molecular dynamics simulation showed that the DELSEED loop was disordered
      by the glycine substitution, whereas it formed an alpha-helix in the alanine
      mutant. Our results emphasize the importance of loop rigidity for efficient
      torque transmissions.

PMID- 23009847
TI  - Structural transformation and physical properties of a hydrogel-forming peptide
      studied by NMR, transmission electron microscopy, and dynamic rheometer.
AB  - Peptide-based hydrogels are attractive biological materials. Study of their self
      assembly pathways from their monomer structures is important not only for
      undertaking the rational design of peptide-based materials, but also for
      understanding their biological functions and the mechanism of many human diseases
      relative to protein aggregation. In this work, we have monitored the
      conformation, morphological, and mechanical properties of a hydrogel-forming
      peptide during hydrogelation in different dimethylsulfoxide (DMSO)/H(2)O
      solutions. The peptide shows nanofiber morphologies in DMSO/H(2)O solution with a
      ratio lower than 4:1. Increased water percentage in the solution enhanced the
      hydrogelation rate and gel strength. One-dimensional and two-dimensional proton
      NMR and electron microscopy studies performed on the peptide in DMSO/H(2)O
      solution with different ratios indicate that the peptide monomer tends to adopt a
      more helical structure during the hydrogelation as the DMSO/H(2)O ratio is
      reduced. Interestingly, at the same DMSO/H(2)O ratio, adding Ca(2+) not only
      promotes peptide hydrogelation and gel strength, but also leads to special shear
      thinning and recovery properties of the hydrogel. Without changing the peptide
      conformation, Ca(2+) binds to the charged Asp residues and induces the change of
      interfiber interactions that play an important role in hydrogel properties.

PMID- 23009848
TI  - Dynamics of forced nucleosome unraveling and role of nonuniform histone-DNA
      interactions.
AB  - A coarse-grained model of the nucleosome is introduced to investigate the
      dynamics of force-induced unwrapping of DNA from histone octamers. In this model,
      the DNA is treated as a charged, discrete worm-like chain, and the octamer is
      treated as a rigid cylinder carrying a positively charged superhelical groove
      that accommodates 1.7 turns of DNA. The groove charges are parameterized to
      reproduce the nonuniform histone/DNA interaction free energy profile and the
      loading rate-dependent unwrapping forces, both obtained from single-molecule
      experiments. Brownian dynamics simulations of the model under constant loading
      conditions reveal that nucleosome unraveling occurs in three distinct stages. At
      small extensions, the flanking DNA exhibits rapid unwrapping-rewrapping
      (breathing) dynamics and the octamer flips ~180 degrees  and moves toward the
      pulling axis. At intermediate extensions, the outer turn of DNA unwraps gradually
      and the octamer swivels about the taut linkers and flips a further ~90 degrees 
      to orient its superhelical axis almost parallel to the pulling axis. At large
      extensions, a portion of the inner turn unwraps abruptly with a notable rip in
      the force-extension plot and a >90 degrees  flip of the octamer. The remaining
      inner turn unwraps reversibly to leave a small portion of DNA attached to the
      octamer despite extended pulling. Our simulations further reveal that the
      nonuniform histone/DNA interactions in canonical nucleosomes serve to: stabilize
      the inner turn against unraveling while enhancing the breathing dynamics of the
      nucleosome and prevent dissociation of the octamer from the DNA while
      facilitating its mobility along the DNA. Thus, the modulation of the histone/DNA
      interactions could constitute one possible mechanism for regulating the
      accessibility of the nucleosome-wound DNA sequences.

PMID- 23009849
TI  - A generalized mathematical model to estimate T- and B-cell receptor diversities
      using AmpliCot.
AB  - The efficiency of the adaptive immune system is dependent on the diversity of T-
      and B-cell receptors, which is created by random rearrangement of receptor gene
      segments. AmpliCot is an experimental technique that allows the measurement of
      the diversity of the T- and B-cell repertoire. This procedure has the advantage
      over other cloning and sequencing techniques of being time- and expense
      effective. In previous studies, receptor diversity, measured with AmpliCot, has
      been inferred assuming a second-order kinetics model. The latter implies that the
      relation between diversity and concentration * time (Cot) values is linear. We
      show that a more detailed model, involving heteroduplex and transient-duplex
      formation, leads to significantly better fits of experimental data and to
      nonlinear diversity-Cot relations. We propose an alternative fitting procedure,
      which is straightforward to apply and which gives an improved description of the
      relationship between Cot values and diversity.

PMID- 23009850
TI  - Contrasting factors on the kinetic path to protein complex formation diminish the
      effects of crowding agents.
AB  - The crowded environment of cells poses a challenge for rapid protein-protein
      association. Yet, it has been established that the rates of association are
      similar in crowded and in dilute solutions. Here we probe the pathway leading to
      fast association between TEM1 beta-lactamase and its inhibitor protein BLIP in
      crowded solutions. We show that the affinity of the encounter complex, the rate
      of final complex formation, and the structure of the transition state are similar
      in crowded solutions and in buffer. The experimental results were reproduced by
      calculations based on the transient-complex theory for protein association. Both
      experiments and calculations suggest that while crowding agents decrease the
      diffusion constant of the associating proteins, they also induce an effective
      excluded-volume attraction between them. The combination of the two opposing
      effects thus results in nearly identical overall association rates in diluted and
      crowded solutions.

PMID- 23009851
TI  - The alpha-helix to beta-sheet transition in stretched and compressed hydrated
      fibrin clots.
AB  - Fibrin is a protein polymer that forms the viscoelastic scaffold of blood clots
      and thrombi. Despite the critical importance of fibrin deformability for outcomes
      of bleeding and thrombosis, the structural origins of the clot's elasticity and
      plasticity remain largely unknown. However, there is substantial evidence that
      unfolding of fibrin is an important part of the mechanism. We used Fourier
      transform infrared spectroscopy to reveal force-induced changes in the secondary
      structure of hydrated fibrin clots made of human blood plasma in vitro. When
      extended or compressed, fibrin showed a shift of absorbance intensity mainly in
      the amide I band (1600-1700 cm(-1)) as well as in the amide II and III bands,
      indicating an increase of the beta-sheets and a corresponding reduction of the
      alpha-helices. The structural conversions correlated directly with the strain or
      pressure and were partially reversible at the conditions applied. The additional
      absorbance observed at 1612-1624 cm(-1) was characteristic of the nascent
      interchain beta-sheets, consistent with protein aggregation and fiber bundling
      during clot deformation observed using scanning electron microscopy. We conclude
      that under extension and/or compression an alpha-helix to beta-sheet conversion
      of the coiled-coils occurs in the fibrin clot as a part of forced protein
      unfolding.

PMID- 23009852
TI  - Single-stranded DNA within nanopores: conformational dynamics and implications
      for sequencing; a molecular dynamics simulation study.
AB  - Engineered protein nanopores, such as those based on alpha-hemolysin from
      Staphylococcus aureus have shown great promise as components of next-generation
      DNA sequencing devices. However, before such protein nanopores can be used to
      their full potential, the conformational dynamics and translocation pathway of
      the DNA within them must be characterized at the individual molecule level. Here,
      we employ atomistic molecular dynamics simulations of single-stranded DNA
      movement through a model alpha-hemolysin pore under an applied electric field.
      The simulations enable characterization of the conformations adopted by single
      stranded DNA, and allow exploration of how the conformations may impact on
      translocation within the wild-type model pore and a number of mutants. Our
      results show that specific interactions between the protein nanopore and the DNA
      can have a significant impact on the DNA conformation often leading to localized
      coiling, which in turn, can alter the order in which the DNA bases exit the
      nanopore. Thus, our simulations show that strategies to control the conformation
      of DNA within a protein nanopore would be a distinct advantage for the purposes
      of DNA sequencing.

PMID- 23009853
TI  - Rigidifying acyl carrier protein domain in iterative type I PKS CalE8 does not
      affect its function.
AB  - Acyl carrier protein (ACP) domains shuttle acyl intermediates among the catalytic
      domains of multidomain type I fatty acid synthase and polyketide synthase (PKS)
      systems. It is believed that the unique function of ACPs is associated with their
      dynamic property, but it remains to be fully elucidated what type of protein
      dynamics is critical for the shuttling domain. Using NMR techniques, we found
      that the ACP domain of iterative type I PKS CalE8 from Micromonospora echinospora
      is highly dynamic on the millisecond-second timescale. Introduction of an
      interhelical disulfide linkage in the ACP domain suppresses the dynamics on the
      millisecond-second timescale and reduces the mobility on the picosecond
      nanosecond timescale. We demonstrate that the full-length PKS is fully functional
      upon rigidification of the ACP domain, suggesting that although the flexibility
      of the disordered terminal linkers may be important for the function of the ACP
      domain, the internal dynamics of the helical regions is not critical for that
      function.

PMID- 23009854
TI  - Inclusion of many-body effects in the additive CHARMM protein CMAP potential
      results in enhanced cooperativity of alpha-helix and beta-hairpin formation.
AB  - Folding simulations on peptides and proteins using empirical force fields have
      demonstrated the sensitivity of the results to details of the backbone potential.
      A recently revised version of the additive CHARMM protein force field, which
      includes optimization of the backbone CMAP potential to achieve good balance
      between different types of secondary structure, correcting the alpha-helical bias
      present in the former CHARMM22/CMAP energy function, is shown to result in
      improved cooperativity for the helix-coil transition. This is due to retention of
      the empirical corrections introduced in the original CMAP to reproduce folded
      protein structures-corrections that capture many-body effects missing from an
      energy surface fitted to gas phase calculations on dipeptides. The experimental
      temperature dependence of helix formation in (AAQAA)(3) and parameters for helix
      nucleation and elongation are in much better agreement with experiment than those
      obtained with other recent force fields. In contrast, CMAP parameters derived by
      fitting to a vacuum quantum mechanical surface for the alanine dipeptide do not
      reproduce the enhanced cooperativity, showing that the empirical backbone
      corrections, and not some other feature of the force field, are responsible. We
      also find that the cooperativity of beta-hairpin formation is much improved
      relative to other force fields we have studied. Comparison with (phi,psi)
      distributions from the Protein Data Bank further justifies the inclusion of many
      body effects in the CMAP. These results suggest that the revised energy function
      will be suitable for both simulations of unfolded or intrinsically disordered
      proteins and for investigating protein-folding mechanisms.

PMID- 23009855
TI  - Functional roles of slow enzyme conformational changes in network dynamics.
AB  - Extensive studies from different fields reveal that many macromolecules,
      especially enzymes, show slow transitions among different conformations. This
      phenomenon is named such things as dynamic disorder, heterogeneity, hysteretic or
      mnemonic enzymes across these different fields, and has been directly
      demonstrated by single molecule enzymology and NMR studies recently. We analyzed
      enzyme slow conformational changes in the context of regulatory networks. A
      single enzymatic reaction with slow conformational changes can filter upstream
      network noises, and can either resonantly respond to the system stimulus at
      certain frequencies or respond adaptively for sustained input signals of the
      network fluctuations. It thus can serve as a basic functional motif with
      properties that are normally for larger intermolecular networks in the field of
      systems biology. We further analyzed examples including enzymes functioning
      against pH fluctuations, metabolic state change of Artemia embryos, and kinetic
      insulation of fluctuations in metabolic networks. The study also suggests that
      hysteretic enzymes may be building blocks of synthetic networks with various
      properties such as narrow-banded filtering. The work fills the missing gap
      between studies on enzyme biophysics and network level dynamics, and reveals that
      the coupling between the two is functionally important; it also suggests that the
      conformational dynamics of some enzymes may be evolutionally selected.

PMID- 23009856
TI  - Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of
      TGF-beta1.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent regulator of
      extracellular matrix production, wound healing, differentiation, and immune
      response, and is implicated in the progression of fibrotic diseases and cancer.
      Extracellular activation of TGF-beta1 from its latent form provides
      spatiotemporal control over TGF-beta1 signaling, but the current understanding of
      TGF-beta1 activation does not emphasize cross talk between activators. Plasmin
      (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of
      TGF-beta1, and in this work we used a systems-level approach with mathematical
      modeling and in vitro experiments to study the interplay between PLS and TSP1 in
      TGF-beta1 activation. Simulations and steady-state analysis predicted a switch
      like bistable transition between two levels of active TGF-beta1, with an inverse
      correlation between PLS and TSP1. In particular, the model predicted that
      increasing PLS breaks a TSP1-TGF-beta1 positive feedback loop and causes an
      unexpected net decrease in TGF-beta1 activation. To test these predictions in
      vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which
      caused proteolytic cleavage of TSP1 and decreased activation of TGF-beta1. The
      TGF-beta1 activation levels showed a cooperative dose response, and a test of
      hysteresis in the cocultured cells validated that TGF-beta1 activation is
      bistable. We conclude that switch-like behavior arises from natural competition
      between two distinct modes of TGF-beta1 activation: a TSP1-mediated mode of high
      activation and a PLS-mediated mode of low activation. This switch suggests an
      explanation for the unexpected effects of the plasminogen activation system on
      TGF-beta1 in fibrotic diseases in vivo, as well as novel prognostic and
      therapeutic approaches for diseases with TGF-beta dysregulation.

PMID- 23009857
TI  - A model of epithelial invagination driven by collective mechanics of identical
      cells.
AB  - We propose a 2D mechanical model of a tubular epithelium resembling the early
      Drosophila embryo. The model consists of a single layer of identical cells with
      energy associated with the tension of cell cortex. Depending on the relative
      tension of the apical, basal, and lateral sides of the cells, tissue thickness,
      and the degree of external constraint, the minimal-energy states of the
      epithelial cross section include circular shapes as well as a range of inward
      buckled shapes. Some of the solutions are characterized by a single deep groove,
      which shows that an epithelium consisting of cells of identical mechanical
      properties can infold. This is consistent with what is seen in embryos of certain
      Drosophila mutants. To ensure that the infolding occurs at a predetermined
      section of the epithelium, we extend the model by increasing the cross-sectional
      area of a subset of cells, which is consistent with observations in wild-type
      embryos. This variation of cell parameters across the epithelium is sufficient to
      make it fold at a specific site. The model explores previously untested minimal
      conditions for tissue invagination and is devoid of specificity needed to
      accurately describe an in vivo situation in Drosophila.

PMID- 23009858
TI  - Cell-to-cell diversity in a synchronized Chlamydomonas culture as revealed by
      single-cell analyses.
AB  - In a synchronized photoautotrophic culture of Chlamydomonas reinhardtii, cell
      size, cell number, and the averaged starch content were determined throughout the
      light-dark cycle. For single-cell analyses, the relative cellular starch was
      quantified by measuring the second harmonic generation (SHG). In destained cells,
      amylopectin essentially represents the only biophotonic structure. As revealed by
      various validation procedures, SHG signal intensities are a reliable relative
      measure of the cellular starch content. During photosynthesis-driven starch
      biosynthesis, synchronized Chlamydomonas cells possess an unexpected cell-to-cell
      diversity both in size and starch content, but the starch-related heterogeneity
      largely exceeds that of size. The cellular volume, starch content, and amount of
      starch/cell volume obey lognormal distributions. Starch degradation was initiated
      by inhibiting the photosynthetic electron transport in illuminated cells or by
      darkening. Under both conditions, the averaged rate of starch degradation is
      almost constant, but it is higher in illuminated than in darkened cells. At the
      single-cell level, rates of starch degradation largely differ but are unrelated
      to the initial cellular starch content. A rate equation describing the cellular
      starch degradation is presented. SHG-based three-dimensional reconstructions of
      Chlamydomonas cells containing starch granules are shown.

PMID- 23009859
TI  - Consequences of mRNA transport on stochastic variability in protein levels.
AB  - Homogeneous cell populations can exhibit considerable cell-to-cell variability in
      protein levels arising from the stochastic nature of the gene-expression process.
      In particular, transcriptional bursting of mRNAs from the promoter has been
      implicated as a major source of stochasticity in the expression of many genes. In
      eukaryotes, transcribed pre-mRNAs have to be exported outside the nucleus and in
      many cases, export rates can be slow and comparable to mRNA turnover rates. We
      investigate whether such export processes can be effective mechanisms in
      buffering protein levels from transcriptional bursting of pre-mRNAs in the
      nucleus. For a stochastic gene-expression model with both transcriptional
      bursting and export, we derive an exact solution of the steady-state probability
      generating function for both the nuclear and the cytoplasmic mRNA levels. These
      formulas reveal that decreasing export rates can dramatically reduce variability
      in cytoplasmic mRNA levels. However, our results also show that decreasing export
      rates enhance mRNA autocorrelation times, which function to increase
      heterogeneity in protein levels. Our overall analysis concludes that under
      physiologically relevant parameter regimes, a pre-mRNA export step can decrease
      steady-state variability at the mRNA level but not at the protein level. Finally,
      we reinforce previous observations that saturation in the pre-mRNA transport
      machinery can be an important mechanism in suppressing protein variability from
      underlying transcriptional bursts.

PMID- 23009860
TI  - Protein logic: a statistical mechanical study of signal integration at the single
      molecule level.
AB  - Information processing and decision-making is based upon logic operations, which
      in cellular networks has been well characterized at the level of transcription.
      In recent years, however, both experimentalists and theorists have begun to
      appreciate that cellular decision-making can also be performed at the level of a
      single protein, giving rise to the notion of protein logic. Here we
      systematically explore protein logic using a well-known statistical mechanical
      model. As an example system, we focus on receptors that bind either one or two
      ligands, and their associated dimers. Notably, we find that a single heterodimer
      can realize any of the 16 possible logic gates, including the XOR gate, by
      variation of biochemical parameters. We then introduce what to our knowledge is a
      novel idea: that a set of receptors with fixed parameters can encode functionally
      unique logic gates simply by forming different dimeric combinations. An
      exhaustive search reveals that the simplest set of receptors (two single-ligand
      receptors and one double-ligand receptor) can realize several different groups of
      three unique gates, a result for which the parametric analysis of single
      receptors and dimers provides a clear interpretation. Both results underscore the
      surprising functional freedom readily available to cells at the single-protein
      level.

PMID- 23009861
TI  - Efficient targeted mutagenesis in the monarch butterfly using zinc-finger
      nucleases.
AB  - The development of reverse-genetic tools in "nonmodel" insect species with
      distinct biology is critical to establish them as viable model systems. The
      eastern North American monarch butterfly (Danaus plexippus), whose genome is
      sequenced, has emerged as a model to study animal clocks, navigational
      mechanisms, and the genetic basis of long-distance migration. Here, we developed
      a highly efficient gene-targeting approach in the monarch using zinc-finger
      nucleases (ZFNs), engineered nucleases that generate mutations at targeted
      genomic sequences. We focused our ZFN approach on targeting the type 2 vertebrate
      like cryptochrome gene of the monarch (designated cry2), which encodes a putative
      transcriptional repressor of the monarch circadian clockwork. Co-injections of
      mRNAs encoding ZFNs targeting the second exon of monarch cry2 into "one nucleus"
      stage embryos led to high-frequency nonhomologous end-joining-mediated, mutagenic
      lesions in the germline (up to 50%). Heritable ZFN-induced lesions in two
      independent lines produced truncated, nonfunctional CRY2 proteins, resulting in
      the in vivo disruption of circadian behavior and the molecular clock mechanism.
      Our work genetically defines CRY2 as an essential transcriptional repressor of
      the monarch circadian clock and provides a proof of concept for the use of ZFNs
      for manipulating genes in the monarch butterfly genome. Importantly, this
      approach could be used in other lepidopterans and "nonmodel" insects, thus
      opening new avenues to decipher the molecular underpinnings of a variety of
      biological processes.

PMID- 23009862
TI  - Intracellular magnesium content decreases during mitochondria-mediated apoptosis
      induced by a new indole-derivative in human colon cancer cells.
AB  - A newly synthesized indole-derivative is able to induce cytostatic and cytotoxic
      effects in the colon cancer cells HT29, effecting apoptosis by activation of an
      intrinsic pathway. Magnesium is involved in both cell growth and apoptosis even
      though its role in the latter process is not well defined. The aims of this work
      were: firstly, to verify if magnesium content is related to the proliferative
      rate in HT29 cells; secondly, to assess the involvement of the cation in
      mitochondria-mediated apoptosis triggered by the new antiproliferative molecule.
      The effects of the indole-derivative in treated cells included cell-cycle arrest
      in the G2/M phase, and apoptotic death confirmed by release of cytochrome c from
      the mitochondrial compartment. Moreover, we demonstrated that the basal content
      of magnesium in HT29 cells inversely correlates with cell saturation density. In
      addition, a decrease in both free and intracellular total magnesium concentration
      was observed along with the induced apoptosis. Taken together, these data suggest
      that magnesium participates in the complex signaling network of cell
      proliferation and apoptosis.

PMID- 23009863
TI  - Physical symptom profile for adult cancer inpatients at a Lebanese cancer unit.
AB  - BACKGROUND: Hospital-based palliative care programs in Lebanon are nonexistent in
      a structured form. One of obstacles is the lack of knowledge about symptom
      prevalence and burden of cancer patients in Lebanon. METHODS: This is a cross
      sectional observational study where 100 adult cancer patients admitted to the
      American University of Beirut Medical Center inpatient unit completed a survey to
      assess 20 physical symptoms according the National Cancer Institute's Common
      Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0) guidelines. RESULTS:
      Hematologic, gastrointestinal, breast, and lung cancers were the most common.
      Mean age was 51.5 years; 51% were female. 74% of patients with solid tumors had
      metastatic disease. Treatment approaches were palliative chemotherapy, followed
      by curative chemotherapy and best supportive care. The most common symptoms were
      fatigue, appetite loss, nausea, and pain; most distressing were nausea, pain, and
      fatigue. Nausea and vomiting were more prevalent among females than males.
      Females reported more severe vomiting than males, but males had more intense
      pain. Overall symptom burden difference was statistically significant across age
      groups, with the 51-60 year group having the most symptoms, but not among
      different genders. Difference was significant among different treatment intents,
      with the best supportive care group having most symptoms. CONCLUSION: Fatigue
      should be better addressed as a legitimate symptom. Subgroup differences must be
      considered when managing gastrointestinal symptoms. Pain should be more
      effectively managed, and vulnerable subgroups such as the 51-60 year age group
      and those on best supportive care should receive special consideration.

PMID- 23009864
TI  - Chemical modification of collagen improves glycosaminoglycan retention of their
      co-precipitates.
AB  - Being prevalent extracellular matrix components, collagen and glycosaminoglycan
      (GAG) are co-precipitated as scaffolds for tissue regeneration. However, the
      amount of GAG incorporated and its long-term retention present a persistent
      problem. In this study, chemical modifications, namely deamination, methylation
      and amination, were used to alter the net charge of collagen prior to fabrication
      of collagen-GAG co-precipitate. While most GAGs were lost in the untreated group
      and the deaminated group within 1 day, methylation and amination of collagen
      retained over 20% and 40% GAG after 6 days, respectively. Moreover, over 60% of
      GAG retention was achieved in the aminated group after cell seeding for 8 days.
      Furthermore, amination of collagen increased the GAG/hydroxyproline ratio in the
      co-precipitate to >4.5, approaching that of native nucleus pulposus.
      Ultrastructural analysis showed that the aminated group contains abundant
      granular substances resembling the extracellular matrix of native nucleus
      pulposus. Despite lower initial cell adhesion than untreated, all modified
      scaffolds promoted proliferation of human mesenchymal stem cells (hMSCs) and
      showed >95% cell viability at all time points. Cell morphology was distinct among
      the different groups, being round in the untreated control and methylated groups
      but elongated in deaminated and aminated groups. hMSCs adhered to scaffolds via
      collagen receptor integrin alpha2beta1 in all groups, while all but the aminated
      group showed extensive expression of the general matrix receptor integrin alphav.
      This work reports an effective method, namely amination of collagen, to improve
      GAG incorporation and retention in collagen-GAG co-precipitates, facilitating the
      fabrication of GAG-rich collagenous scaffold for intervertebral disc tissue
      engineering.

PMID- 23009865
TI  - The relationship of reported neighborhood conditions with child mental health.
AB  - OBJECTIVE: Although in many studies authors have documented the relationship
      between neighborhood socioeconomic status and child mental health, few have
      examined the association between neighborhood conditions and mental health
      disorders. The objective of this study was to determine whether parent-reported
      neighborhood conditions are associated with common child mental health disorders.
      METHODS: We analyzed data on children ages 6 to 17 (N = 64,076) collected through
      the 2007 National Survey of Children's Health. Primary outcome variables were a
      child being reported to have a diagnosis of (1) anxiety and/or depression and (2)
      attention-deficit-hyperactivity disorder (ADHD) and/or disruptive behavior. Main
      independent variables were parent-reported neighborhood amenities (eg, recreation
      center), poor physical characteristics (eg, dilapidated housing), social
      support/trust, neighborhood safety, and school safety. Multivariate logistic
      regression analyses were conducted to examine associations between neighborhood
      conditions and (1) anxiety/depression and (2) ADHD/disruptive behavior. RESULTS:
      Children living in a neighborhood with 3 poor physical characteristics had
      greater odds of anxiety/depression (adjusted odds ratio [AOR] 1.58, 95%
      confidence interval [95% CI] 1.01-2.46) and ADHD/disruptive behavior (AOR 1.44,
      95% CI 1.04-1.99) compared with children living in a neighborhood with no poor
      physical characteristics. Children of parents who reported living in a
      neighborhood with low social support/trust had greater odds of depression/anxiety
      (AOR 1.71, 95% CI 1.28-2.30) and ADHD/disruptive behavior (AOR 1.47, 95% CI 1.19
      1.81) than children living in a neighborhood with greater social support/trust.
      CONCLUSIONS: Parent perception of neighborhood social support/trust and physical
      characteristics may be important to assess in clinical settings and should be
      examined in future study of child mental health burden.

PMID- 23009867
TI  - Transperineal management for postoperative and radiation rectourethral fistulas.
AB  - PURPOSE: The rectal sphincter preserving transperineal approach has been
      increasingly used successfully. We analyzed our experience with this surgical
      approach. A secondary aim was to evaluate the surgical outcome of energy ablative
      rectourethral fistulas without a concomitant interposition muscle flap. MATERIALS
      AND METHODS: We identified all patients with rectourethral fistula who underwent
      rectal sphincter preserving transperineal repair from 1998 to 2011. Re
      approximation of the urethral mucosa, posterior anastomotic urethroplasty or
      partial/total prostatectomy with urethrovesical anastomosis was performed for
      urinary closure. The fistula cohort was divided into 2 groups, including
      postoperative and energy ablative fistulas, respectively. Success after perineal
      rectourethral fistula repair was defined as resolution after the first attempt at
      repair. RESULTS: A total of 23 patients underwent rectal sphincter preserving,
      transperineal rectourethral fistula repair. In the postoperative fistula cohort
      the fistula was successfully resolved in all 10 patients. A dartos interposition
      muscle flap was used in 2 of 10 patients. In the energy ablative cohort the
      fistula was successfully closed in 8 of 13 patients. An interposition muscle flap
      was not placed in 8 patients with an energy ablative fistula, of whom success was
      achieved in 5. Two of the 5 patients with an energy ablative fistula and a
      successful outcome without a concomitant interposition muscle flap had urinary
      extravasation, necessitating temporary catheterization. CONCLUSIONS: Rectal
      sphincter preserving transperineal repair is a successful surgical method to
      repair postoperative and energy ablative rectourethral fistulas. An interposition
      muscle flap should be considered in the setting of energy ablative rectourethral
      fistulas to increase successful outcomes.

PMID- 23009866
TI  - Imaging the clear cell renal cell carcinoma proteome.
AB  - PURPOSE: A key barrier to identifying tissue biomarkers of clear cell renal cell
      carcinoma is the heterogeneity of protein expression in tissue. However, by
      providing spectra for every 0.05 mm(2) area of tissue, imaging mass spectrometry
      reveals the spatial distribution of peptides. We determined whether this approach
      could be used to identify and map protein signatures of clear cell renal cell
      carcinoma. MATERIALS AND METHODS: We constructed 2 tissue microarrays with 2
      cores each of matched tumor and normal tissue from the nephrectomy specimens of
      70 patients with clear cell renal cell carcinoma. Samples were analyzed by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry. In each
      tissue microarray peptide signatures were identified that differentiated cancer
      from normal tissue. The signatures were then cross validated. Mass
      spectrometry/mass spectrometry sequencing was performed to determine the identity
      of select, differentially expressed peptides. Immunohistochemistry was used for
      validation. RESULTS: In each tissue microarray peptide signatures were identified
      that had 94.7% to 98.5% classification accuracy for each 0.05 mm(2) spot
      (spectrum) and 96.9% to 100% accuracy for each tissue core. Cross validation
      across tissue microarrays revealed a classification accuracy of 82.6% to 84.7%
      for each spot and 88.9% to 92.4% for each core. We identified vimentin, histone
      2A.X and alpha-enolase as proteins with greater expression in cancer tissue. This
      was validated by immunohistochemistry. CONCLUSIONS: Imaging mass spectrometry
      identified and mapped specific peptides that accurately distinguished malignant
      from normal renal tissue. This demonstrates its potential as a novel, high
      throughput approach to clear cell renal cell carcinoma biomarker discovery. Given
      the multiple pathways and known heterogeneity involved in tumors such as clear
      cell renal cell carcinoma, multiple peptide signatures that maintain their
      spatial relationships may outperform traditional protein biomarkers.

PMID- 23009868
TI  - Frequency of the male infertility evaluation: data from the national survey of
      family growth.
AB  - PURPOSE: An estimated 7 million American couples per year seek infertility care
      in the United States. A male factor contributes to 50% of cases but it is unclear
      what proportion of infertile couples undergoes male evaluation. MATERIALS AND
      METHODS: We analyzed data from cycles 5 to 7 of the National Survey of Family
      Growth performed by the Centers for Disease Control to determine the frequency of
      a male infertility evaluation, and associated reproductive and demographic
      factors. RESULTS: A total of 25,846 women and 11,067 men were surveyed. Male
      evaluation was not completed in 18% of couples when the male partner was asked vs
      27% when female partners were asked. This corresponds to approximately 370,000 to
      860,000 men in the population who were not evaluated at the time of infertility
      evaluation. Longer infertility duration and white race were associated with
      increased odds of male infertility evaluation. The male and female samples showed
      no change in the receipt of male examination with time. CONCLUSIONS: Many men
      from infertile couples do not undergo male evaluation in the United States. Given
      the potential implications to reproductive goals and male health, further
      examination of this pattern is warranted.

PMID- 23009869
TI  - Drain placement can be safely omitted after the majority of robotic partial
      nephrectomies.
AB  - PURPOSE: Drain placement after partial nephrectomy is considered standard but it
      is based on routine and not on evidence. With experience we performed robotic
      partial nephrectomy and routinely omitted a drain even with significant
      collecting system violation. We have rarely used drains after robotic partial
      nephrectomy for several years, and we report our outcomes. MATERIALS AND METHODS:
      We reviewed a single surgeon, prospective database of all robotic partial
      nephrectomies from February 2008 to March 2012, including the characteristics of
      those with and without a drain. RESULTS: The 150 patients underwent a total of
      160 robotic partial nephrectomy procedures with a drain used in 11 patients and
      omitted in 93%. Mean patient age was 57 years (range 22 to 89), mean American
      Society of Anesthesiologists score was 2.8 (range 2 to 4) and mean body mass
      index was 32 kg/m(2) (range 18 to 54). Values were similar in patients with and
      without a drain. In patients without a drain and in those with a drain mean tumor
      size was 3.5 cm (range 1.0 to 11.0) and 4.6 cm (range 1.1 to 8.6), and mean
      R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system
      or sinus, anterior/posterior, location relative to polar lines, hilar tumor
      touching main renal artery or vein) nephrometry score was 7.8 (range 4 to 12) and
      8.8 (range 6 to 11), respectively. Collecting system violation occurred in 88
      patients (59%), including 78 without a drain. Two patients (1.3%) required
      transfusion with no intervention for bleeding. All except 5 patients (97%) were
      discharged home on postoperative day 1 with all drains removed before discharge.
      In 2 patients (1.3%) without a drain small urinomas without infection developed
      more than 2 weeks postoperatively, which were treated with a week of Foley
      catheter drainage and percutaneous drainage, respectively. CONCLUSIONS: Drain
      placement after robotic partial nephrectomy can be routinely omitted with a low
      rate of urine leaks, which can be managed safely when they rarely occur.

PMID- 23009870
TI  - Urinary diversion practice patterns among certifying American urologists.
AB  - PURPOSE: We investigated trends in urinary diversion use and surgeon
      characteristics in the performance of incontinent and continent urinary diversion
      using American Board of Urology data. MATERIALS AND METHODS: Annualized case log
      data for urinary diversion were obtained from the American Board of Urology for
      urologists who certified or recertified from 2002 to 2010. We evaluated the
      association between surgeon characteristics and the performance of any urinary
      diversion or the type of urinary diversion. RESULTS: Of the 5,096 certifying or
      recertifying urologist case logs examined 1,868 (37%) urologists performed any
      urinary diversion. The median number of urinary diversions was 4 per year (IQR 2,
      6) and 222 urologists (4%) performed 10 or more per year. On multivariate
      analysis younger urologists, those self-identified as oncologists or female
      urologists, those who certified in more recent years and those in larger practice
      areas or outside the Northeast region of the United States were more likely to
      perform any urinary diversion. Only 9% of the total cohort (471 urologists)
      performed any continent urinary diversion. The likelihood of performing any
      continent urinary diversion increased with the number of urinary diversions (p
      <0.0001). As urinary diversion volume increased, the proportion representing
      continent urinary diversion also increased (p <0.0005). Surgeons in private
      practice settings and those in the Northeast were less likely to perform
      continent urinary diversion. CONCLUSIONS: Few urologists perform any urinary
      diversion. Continent urinary diversion is most frequently done by high volume
      surgeons. The type of urinary diversion that a patient receives may depend in
      part on surgeon characteristics.

PMID- 23009871
TI  - Risk factors and prevention of inguinal hernia after radical prostatectomy: a
      systematic review and meta-analysis.
AB  - PURPOSE: Inguinal hernia is widely recognized as a complication after radical
      prostatectomy. We systematically investigated the risk factors for inguinal
      hernia, compared the incidence after various surgical procedures and explored
      prophylactic surgical maneuvers. MATERIALS AND METHODS: A systematic search of
      the literature was performed using Medline(r), Web of Knowledge(r) and the
      Cochrane Library databases. All analyses and tests were conducted using STATA(r)
      software. RESULTS: A total of 31 trials from 29 eligible studies were identified
      according to the predefined selection criteria. As integrated, postoperative
      inguinal hernia developed in 15.9% (13.1-18.7) of patients who underwent radical
      retropubic prostatectomy and 6.7% (4.8-8.6) of those who underwent laparoscopic
      radical prostatectomy. Most cases of inguinal hernia occurred within the first 2
      years after surgery. Right side and indirect-type dominance was found in those
      inguinal hernias. Pooled results of comparative studies revealed that the
      incidence of inguinal hernia after radical retropubic prostatectomy was
      significantly higher than that after no operation, laparoscopic surgery, radical
      perineal prostatectomy, mini-laparotomy radical retropubic prostatectomy and
      pelvic lymph node dissection, but was not significantly higher than that after
      open prostatectomy and cystectomy. In addition, increasing age, low body mass
      index, subclinical inguinal hernia, previous inguinal hernia repair and
      anastomotic stricture can increase the risk for inguinal hernia after radical
      prostatectomy. CONCLUSIONS: While some limitations cannot be overcome, this meta
      analysis suggests that damage to the posterior layer of the rectus sheath may be
      involved in the development of inguinal hernia after radical prostatectomy.
      Prophylactic surgery for high risk subjects is advised at the time of radical
      prostatectomy to minimize the incidence of inguinal hernia.

PMID- 23009872
TI  - Cryoablation versus minimally invasive partial nephrectomy for small renal masses
      in the solitary kidney: impact of approach on functional outcomes.
AB  - PURPOSE: We evaluated the change in renal function after renal cryoablation and
      partial nephrectomy based on tumor complexity according to the R.E.N.A.L.
      nephrometry score. MATERIALS AND METHODS: We retrospectively reviewed the data of
      patients who had a renal tumor in a solitary kidney, and underwent renal
      cryoablation and partial nephrectomy between December 2000 and January 2012.
      Renal tumor complexity was categorized into 3 groups by R.E.N.A.L. nephrometry
      score as low (4 to 6), intermediate (7 to 9) and high (10 to 12). All baseline
      demographic data, perioperative parameters and followup data including renal
      function were collected. Comparisons were made among similar tumor complexities.
      RESULTS: In the renal cryoablation and partial nephrectomy groups 29 patients (43
      tumors) and 33 patients were identified, respectively. In all renal tumor
      complexities, renal cryoablation provided a better perioperative outcome in terms
      of median operative time, estimated blood loss, transfusion, hospital stay and
      complications. The median change in serum creatinine and estimated glomerular
      filtration rate was slightly greater in the partial nephrectomy group. However,
      the differences were not statistically significant for any of the tumor
      complexities. Three patients (10%) in the renal cryoablation group and 2 (6%) in
      the partial nephrectomy group required long-term dialysis. CONCLUSIONS: In
      patients with solitary kidneys, renal cryoablation is associated with superior
      perioperative outcomes compared to partial nephrectomy. Specifically, partial
      nephrectomy is not associated with greater loss of renal function than renal
      cryoablation regardless of the extent of tumor complexity.

PMID- 23009873
TI  - Combined ciprofloxacin and amikacin prophylaxis in the prevention of septicemia
      after transrectal ultrasound guided biopsy of the prostate.
AB  - PURPOSE: A steady increase in the incidence of septicemia after prostate biopsy
      in our unit between 2001 and 2005 prompted us to review our prophylactic
      antibiotic regimen. We compared the incidence of septicemia in patients
      undergoing prostate biopsy between 2001 and 2005 when only oral ciprofloxacin was
      used prophylactically (group 1) to the incidence among patients undergoing biopsy
      between 2006 and 2010 when a single dose of intravenous amikacin was added to
      ciprofloxacin (group 2). MATERIALS AND METHODS: In group 1 the 300 patients were
      given 500 mg oral ciprofloxacin twice daily 1 day before and for 2 days after the
      biopsy while in group 2 the 897 patients, in addition to the ciprofloxacin
      previously mentioned, received 500 mg intravenous amikacin 30 minutes before the
      biopsy. Patients admitted to the hospital with septicemia after prostate biopsy
      had urine and blood culture and sensitivity tests. The number of patients in whom
      septicemia developed in each group after prostate biopsy and the microorganisms
      isolated from the urine and blood of such patients were compared using the chi
      square test. RESULTS: Septicemia was seen in 24 of 300 (8%) and 15 of 897 (1.7%)
      patients in groups 1 and 2, respectively (p <0.001). In group 1 the rate of
      septicemia after prostate biopsy was 2.1% and 13% in 2001 and 2005, respectively
      (p <0.001). In group 2 the rate of septicemia was 1.5% in 2006 and 1.6% in 2010
      (p <0.25). Escherichia coli resistant to quinolones was responsible for 33 of 39
      (84.6%) septicemic cases. CONCLUSIONS: The addition of amikacin to ciprofloxacin
      prophylaxis significantly reduces the incidence of septicemia after prostate
      biopsy.

PMID- 23009874
TI  - Production of toxic pavettamine and pavettamine conjugates in the gousiekte
      causing Fadogia homblei plant and its relation to the bacterial endosymbiont.
AB  - Plant poisoning of livestock is responsible for considerable economic losses in
      southern Africa. Six plant species of the Rubiaceae family are known to cause
      gousiekte, a cardiac syndrome of ruminants induced by ingestion of the toxic
      compound pavettamine. Progress in understanding the etiology of this disease is
      largely hampered by the variable toxicity of the plants and the absence of a
      quantification method for pavettamine. The pavettamine concentration in leaf
      samples of Fadogia homblei, a known gousiekte causing plant, was analyzed by mass
      spectrometry. In the most apical leaf pair, the highest concentration of
      pavettamine was detected. Distal leaves contained progressively less pavettamine.
      Besides a significant amount of free pavettamine, most pavettamine was found to
      occur in a conjugated form. To which molecules the pavettamine is conjugated
      remains unknown as is the function of conjugated pavettamine in the development
      of gousiekte. All know gousiekte-causing plants contain symbiotic bacteria in
      their leaves; it was hypothesized that these bacteria might be involved in the
      production of pavettamine. However, analysis of in vitro cultures of the F.
      homblei endosymbiont revealed no production of pavettamine. Pavettamine is
      therefore not produced by the bacteria alone. It is either the product of the
      interaction with the plant or solely produced by the host.

PMID- 23009875
TI  - Chemical constituents from Brucea javanica.
AB  - Fourteen apotirucallane-type triterpenoids, named brujavanones A-N, were isolated
      from the twigs of Brucea javanica, along with four known quassinoids and seven
      known lignans from the seeds of B. javanica. Their structures were elucidated on
      the basis of extensive spectroscopic data analysis. The structure of a previously
      reported triterpenoid, bruceajavanin C, was revised as its C-21 epimer. The
      cytotoxic activities of triterpenoids and quassinoids against two human tumor
      cell lines, HL-60 and A-549, were evaluated, but all the compounds were inactive
      (IC50>10 MUM).

PMID- 23009876
TI  - Myrosinases TGG1 and TGG2 from Arabidopsis thaliana contain exclusively
      oligomannosidic N-glycans.
AB  - In all eukaryotes N-glycosylation is the most prevalent protein modification of
      secretory and membrane proteins. Although the N-glycosylation capacity and the
      individual steps of the N-glycan processing pathway have been well studied in the
      model plant Arabidopsis thaliana, little attention has been paid to the
      characterization of the glycosylation status of individual proteins. We report
      here the structural analysis of all N-glycans present on the endogenous
      thioglucoside glucohydrolases (myrosinases) TGG1 and TGG2 from A. thaliana. All
      nine glycosylation sites of TGG1 and all four glycosylation sites of TGG2 are
      occupied by oligomannosidic structures with Man5GlcNAc2 as the major glycoform.
      Analysis of the oligomannosidic isomers from wild-type plants and mannose
      trimming deficient mutants by liquid chromatography with porous graphitic carbon
      and mass spectrometry revealed that the N-glycans from both myrosinases are
      processed by Golgi-located alpha-mannosidases.

PMID- 23009877
TI  - Bisabololoxide derivatives from Artemisia persica, and determination of their
      absolute configurations by ECD.
AB  - Five antiplasmodial bisabololoxide sesquiterpene diesters were isolated from an
      EtOAc extract of the aerial parts of Artemisia persica following an HPLC-time
      based activity profiling of the extract. Structure elucidation was achieved by 1D
      and 2D NMR experiments. Relative configurations of cyclohexenone/cyclohexene and
      tetrahydropyran moieties of 1-5 were established on the basis of 3J(H-H) coupling
      constants and NOE difference spectra. Stereochemical correlation of the two
      rings, and assignment of absolute configuration of 1-5 were achieved by
      comparison of experimental ECD spectra with simulated ECD data for possible
      stereoisomers, by using time dependent density function theory (TDDFT).
      Bisaboloids 1-4 exhibited in vitro antimalarial activity against Plasmodium
      falciparum, with IC50 values ranging from 2.8 to 20.1 MUM, and selectivity
      indices (SI) in L-6 cells of 3.7-11.9.

PMID- 23009878
TI  - Functional characterization of wheat copalyl diphosphate synthases sheds light on
      the early evolution of labdane-related diterpenoid metabolism in the cereals.
AB  - Two of the most agriculturally important cereal crop plants are wheat (Triticum
      aestivum) and rice (Oryza sativa). Rice has been shown to produce a number of
      diterpenoid natural products as phytoalexins and/or allelochemicals-
      specifically, labdane-related diterpenoids, whose biosynthesis proceeds via
      formation of an eponymous labdadienyl/copalyl diphosphate (CPP) intermediate
      (e.g., the ent-CPP of gibberellin phytohormone biosynthesis). Similar to rice,
      wheat encodes a number of CPP synthases (CPS), and the three CPS characterized to
      date (TaCPS1-3) all have been suggested to produce ent-CPP. However, several of
      the downstream diterpene synthases will only react with CPP intermediate of
      normal or syn, but not ent, stereochemistry, as described in the accompanying
      report. Investigation of additional CPS did not resolve this issue, as the only
      other functional synthase (TaCPS4) also produced ent-CPP. Chiral product
      characterization of all the TaCPS then established that TaCPS2 uniquely produces
      normal, rather than ent-, CPP, thus, providing a suitable substrate source for
      the downstream diterpene synthases. Notably, TaCPS2 is most homologous to the
      similarly stereochemically differentiated syn-CPP synthase from rice (OsCPS4),
      while the non-inducible TaCPS3 and TaCPS4 cluster with the rice OsCPS1 required
      for gibberellin phytohormone biosynthesis, as well as with a barley (Hordeum
      vulgare) CPS (HvCPS1) that also is characterized here as similarly producing ent
      CPP. These results suggest that diversification of labdane-related diterpenoid
      metabolism beyond the ancestral gibberellins occurred early in cereal evolution,
      and included the type of stereochemical variation demonstrated here.

PMID- 23009880
TI  - Triterpenoid glycosides from the stems of Gordonia kwangsiensis.
AB  - Eleven oleanane-type triterpenoid glycosides, named gordonsaponins A-K, were
      isolated from the stems of Gordonia kwangsiensis. Their structures were
      elucidated by spectroscopic and chemical methods. The cytotoxic activities of all
      eleven were evaluated against five human tumor cell lines (HCT-8, Bel-7402, BGC
      823, A549, and A2780), with only one having activity against all tested cell
      lines, with IC50 values ranging from 0.1 to 2.41 MUM.

PMID- 23009879
TI  - Functional characterization of wheat ent-kaurene(-like) synthases indicates
      continuing evolution of labdane-related diterpenoid metabolism in the cereals.
AB  - Wheat (Triticum aestivum) and rice (Oryza sativa) are two of the most
      agriculturally important cereal crop plants. Rice is known to produce numerous
      diterpenoid natural products that serve as phytoalexins and/or allelochemicals.
      Specifically, these are labdane-related diterpenoids, derived from a
      characteristic labdadienyl/copalyl diphosphate (CPP), whose biosynthetic
      relationship to gibberellin biosynthesis is evident from the relevant expanded
      and functionally diverse family of ent-kaurene synthase-like (KSL) genes found in
      rice the (OsKSLs). Herein reported is the biochemical characterization of a
      similarly expansive family of KSL from wheat (the TaKSLs). In particular, beyond
      ent-kaurene synthases (KS), wheat also contains several biochemically diversified
      KSLs. These react either with the ent-CPP intermediate common to gibberellin
      biosynthesis or with the normal stereoisomer of CPP that also is found in wheat
      (as demonstrated by the accompanying paper describing the wheat CPP synthases).
      Comparison with a barley (Hordeum vulgare) KS indicates conservation of monocot
      KS, with early and continued expansion and functional diversification of KSLs in
      at least the small grain cereals. In addition, some of the TaKSLs that utilize
      normal CPP also will react with syn-CPP, echoing previous findings with the OsKSL
      family, with such enzymatic promiscuity/elasticity providing insight into the
      continuing evolution of diterpenoid metabolism in the cereal crop plant family,
      as well as more generally, which is discussed here.

PMID- 23009881
TI  - Effects of pregabalin on sleep in generalized anxiety disorder.
AB  - Sleep disturbance is a cardinal symptom in both DSM-IV and ICD-10 criteria for
      generalized anxiety disorder (GAD). This review summarizes the results of
      clinical trials and pooled analyses that provide data on pregabalin's effect on
      sleep disturbance in patients diagnosed with GAD. The hypothesized mechanism of
      action of pregabalin is distinctly different from other anxiolytics. Pregabalin
      binds to a membrane alpha2delta subunit protein to inhibit release in excited
      central nervous system neurons of neurotransmitters implicated in pathological
      anxiety. Treatment with pregabalin has been found to be associated with
      significant improvement in GAD-related sleep disturbance across seven placebo
      controlled clinical trials. Treatment with pregabalin is associated with
      improvement in all forms of insomnia and improvement in sleep has been found to
      be correlated with reduction in functional impairment and improvement in quality
      of life on subjective global measures. Results of a mediational analysis suggest
      that 53% of the effect of pregabalin on sleep disturbance was due to a direct
      effect and 47% was due to an indirect effect, mediated through prior reduction in
      anxiety symptom severity. In patients with GAD, improvement in sleep has been
      found to be associated with a reduction in daytime sleepiness. However, dose
      related sedation is reported, typically in the first 2 wk of treatment, in
      approximately 10-30% of patients, depending on the dose used and the speed of
      titration. Insomnia is a common component of the clinical presentation of GAD and
      pregabalin appears to be an efficacious treatment for this often chronic and
      disabling symptom.

PMID- 23009882
TI  - Biochemical characterization of a new recombinant TNF receptor-hyFc fusion
      protein expressed in CHO cells.
AB  - The currently used Tumor Nectosis Factor (TNF)-alpha blockers such as infliximab,
      adalimumab and etanercept have Fc regions of the human IgG1 subtype have
      advantages in terms of in vivo half-life, however these could raise potential
      concerns for unwanted effector-mediated effects, such as antibody dependent
      cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). To
      address this issue, we constructed a novel hybrid protein with decreased ADCC and
      CDC potentials by fusing the TNF receptor to a hybrid Fc (hyFc) containing CH2
      and CH3 regions of IgG4 and highly flexible hinge regions of IgD which neither
      has ADCC and CDC activities. The resulting fusion protein, TNFR-hyFc, was over
      expressed in CHO cells. For use as a pre-clinical material in pharmacology, PK
      and toxicological evaluations were carried out for biochemical characterization
      which was then compared with etanercept that has similarity in structure. Amino
      acid composition analysis and peptide mapping showed that the expressed TNFR-hyFc
      matched the theoretical composition derived from the DNA sequence. Matrix
      assisted laser desorption/ionization-time of flight (MALDI-TOF) showed that TNFR
      hyFc is 2.9 kDa larger than etanercept. MALDI-TOF after removal of N-glycans by
      PNGase treatment showed that TNFR-hyFc is 3.9 kDa larger than etanercept.
      Isoelectric focusing and monosaccharide analysis showed that TNFR-hyFc is
      slightly more acidic than etanercept. N-terminal amino acid sequencing showed
      that N-terminal heterogeneity is present in both TNFR-hyFc and etanercept,
      although the ratios are somewhat different. Glycan analysis showed that the main
      glycan form is bi-antennary, similar to etanercept.

PMID- 23009883
TI  - Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year
      drinking water exposure.
AB  - Acrylamide is a component of roasted coffee and certain baked and fried
      carbohydrate-rich foods prepared at high temperatures. We have assessed the
      carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats
      administered 0, 0.0875, 0.175, 0.35, or 0.70mM acrylamide in the drinking water
      ad libitum for 2 years. Acrylamide caused significant dose-related decreasing
      trends in the body weights of F344/N rats. Acrylamide administration resulted in
      significant dose-related decreasing trends in survival in both sexes of B6C3F(1)
      mice and in female F344/N rats. Histopathological analyses indicated significant
      dose-related increases in Harderian gland and lung tumors in male and female
      B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of
      forestomach tumors, while female B6C3F(1) mice had significant dose-related
      increases in mammary gland, ovary, and skin tumors. In male and female F344/N
      rats, there were significant increases in thyroid tumors. Male F344/N rats also
      had significant dose-related increases in testes, heart, and pancreas tumors,
      while female F344 rats demonstrated significant increases in clitoral gland,
      mammary gland, oral cavity, and skin tumors. These results, combined with
      previous mechanistic studies, provide strong support for the concept that
      acrylamide is activated to a carcinogen through metabolism to glycidamide.

PMID- 23009884
TI  - Safety evaluation of some wild plants in the New Nordic Diet.
AB  - One of the dietary components in the New Nordic Diet, is plants from the wild
      countryside. However, these may have a high content of bioactive components, some
      of which could be toxic in larger quantities. The objective of this paper is to
      outline a strategy for safety evaluation of wild plants not covered in current
      food compositional databases and to apply the method for selected plants used in
      the New Nordic Diet recipes. Four examples of typical wild edible plants were
      evaluated (stinging nettle, sorrel, chickweed and common lambsquarters), and
      based on substantial equivalence with known food plants the majority of the
      bioactive components reported were within the range experienced when eating or
      drinking typical food stuffs. For most compounds the hazards could be evaluated
      as minor. The only precaution found was for common lambsquarters because of its
      presumed high level of oxalic acid. It is concluded that a substance-by-substance
      evaluation of intake by equivalence to common foods is a useful and efficient
      strategy to evaluate the safety of newly introduced wild edible plants. Further
      evaluation and better compositional analyses are warranted before a daily
      consumption of significant amounts of wild edible plants can be generally
      regarded as safe.

PMID- 23009885
TI  - Buccal versus lingual mucosal graft urethroplasty for complex hypospadias repair.
AB  - OBJECTIVES: To compare surgical outcomes and donor site complications of buccal
      and lingual mucosa used as ventral onlay graft for complex hypospadias cases.
      PATIENTS & METHODS: Forty four cases with complex hypospadias after failed
      previous surgery were prospectively included. All had severely scarred penile
      skin with reasonable residual urethral plate. Cases were categorized into two
      groups: Group I (23) where buccal mucosal graft [BMG] was used and group II (21)
      where lingual mucosal graft [LMG] was used. Donor site complications as well as
      functional and esthetic outcomes were recorded for each group. RESULTS: Mean
      follow up was 20.8 months (range 12-24). Average graft harvesting time was 24 min
      for BMG and 19 min for LMG. Donor site pain was reported with both techniques but
      recovery was earlier with LMG. Slurred speech and difficult tongue protrusion
      were reported with lingual but not buccal grafts; however mouth tightness, peri
      oral numbness and persistent oral discomfort were reported only with buccal
      grafts. Successful urethroplasty was obtained in 78.2% of BMG compared to 76.1%
      of LMG. CONCLUSION: Surgical outcomes of LMG urethroplasty were comparable to
      those of BMG in complex hypospadias cases. Compared to buccal mucosa, LMG is easy
      to harvest, with minimal donor site complications.

PMID- 23009886
TI  - A review of current statistical methodologies for in-storage sampling and
      surveillance in the grains industry.
AB  - Effective, statistically robust sampling and surveillance strategies form an
      integral component of large agricultural industries such as the grains industry.
      Intensive in-storage sampling is essential for pest detection, integrated pest
      management (IPM), to determine grain quality and to satisfy importing nation's
      biosecurity concerns, while surveillance over broad geographic regions ensures
      that biosecurity risks can be excluded, monitored, eradicated or contained within
      an area. In the grains industry, a number of qualitative and quantitative
      methodologies for surveillance and in-storage sampling have been considered.
      Primarily, research has focussed on developing statistical methodologies for in
      storage sampling strategies concentrating on detection of pest insects within a
      grain bulk; however, the need for effective and statistically defensible
      surveillance strategies has also been recognised. Interestingly, although
      surveillance and in-storage sampling have typically been considered
      independently, many techniques and concepts are common between the two fields of
      research. This review aims to consider the development of statistically based in
      storage sampling and surveillance strategies and to identify methods that may be
      useful for both surveillance and in-storage sampling. We discuss the utility of
      new quantitative and qualitative approaches, such as Bayesian statistics, fault
      trees and more traditional probabilistic methods and show how these methods may
      be used in both surveillance and in-storage sampling systems.

PMID- 23009887
TI  - Impact of cytokine and cytokine receptor gene polymorphisms on cellular immunity
      after smallpox vaccination.
AB  - We explored associations between SNPs in cytokine/cytokine receptor genes and
      cellular immunity in subjects following primary smallpox vaccination. We also
      analyzed the genotype-phenotype associations discovered in the Caucasian subjects
      among a cohort of African-Americans. In Caucasians we found 277 associations
      (p<0.05) between gene SNPs and inter-individual variations in IFN-alpha, IL
      12p40, IL-1beta, IL-2, and TNF-alpha secretion levels. A collection of SNPs in
      the IL1RN, IL2RB, IL4R, IL6, IL10RB, IL12A, and IL12RB2 genes had consistent
      associations among both Caucasians and African-Americans. A regulatory SNP
      (rs452204) in the IL1RN gene was significantly associated with higher levels of
      IL-2 secretion in an allele dose-dependent manner in both race groups (p=0.05 for
      Caucasians and p=0.002 for African-Americans). IL12RB2 polymorphism rs3790567 was
      associated with a dose-related decrease in IL-1beta secretion (p=0.009 for
      Caucasians and p=0.01 for African-Americans). Our results demonstrate that
      variations in smallpox vaccine-induced cytokine responses are modulated by
      genetic polymorphisms in cytokine and cytokine receptor genes.

PMID- 23009888
TI  - Classification algorithms based on anterior segment optical coherence tomography
      measurements for detection of angle closure.
AB  - OBJECTIVE: A recent study found that a combination of 6 anterior segment optical
      coherence tomography (ASOCT) parameters (anterior chamber area, volume, and width
      [ACA, ACV, ACW], lens vault [LV], iris thickness at 750 MUm from the scleral
      spur, and iris cross-sectional area) explain >80% of the variability in angle
      width. The aim of this study was to evaluate classification algorithms based on
      ASOCT measurements for the detection of gonioscopic angle closure. DESIGN: Cross
      sectional study. PARTICIPANTS: We included 2047 subjects aged >=50 years.
      METHODS: Participants underwent gonioscopy and ASOCT (Carl Zeiss Meditec, Dublin,
      CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China)
      was used to measure ASOCT parameters in horizontal ASOCT scans. Six
      classification algorithms were considered (stepwise logistic regression with
      Akaike information criterion, Random Forest, multivariate adaptive regression
      splines, support vector machine, naive Bayes' classification, and recursive
      partitioning). The ASOCT-derived parameters were incorporated to generate point
      and interval estimates of the area under the receiver operating characteristic
      (AUC) curves for these algorithms using 10-fold cross-validation as well as 50:50
      training and validation. MAIN OUTCOME MEASURES: We assessed ASOCT measurements
      and angle closure. RESULTS: Data on 1368 subjects, including 295 (21.6%) subjects
      with gonioscopic angle closure were available for analysis. The mean (+/-standard
      deviation) age was 62.4+/-7.5 years and 54.8% were females. Angle closure
      subjects were older and had smaller ACW, ACA, and ACV; greater LV; and thicker
      irides (P<0.001 for all). For both, the 10-fold cross-validation and the 50:50
      training and validation methods, stepwise logistic regression was the best
      algorithm for detecting eyes with gonioscopic angle closure with testing set AUC
      of 0.954 (95% confidence interval [CI], 0.942-0.966) and 0.962 (95% CI, 0.948
      0.975) respectively, whereas recursive partitioning had relatively the poorest
      performance with testing set AUC 0.860 (95% CI, 0.790-0.930) and 0.905 (95% CI,
      0.876-0.933), respectively. This algorithm performed similarly well (AUC, 0.957)
      in a second independent sample of 200 angle closure subjects and 302 normal
      controls. CONCLUSIONS: A classification algorithm based on stepwise logistic
      regression that used a combination of 6 parameters obtained from a single
      horizontal ASOCT scan identified subjects with gonioscopic angle closure>95% of
      the time. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial
      interest in any of the materials discussed in this article.

PMID- 23009889
TI  - Wide-field spectral-domain optical coherence tomography in patients and carriers
      of X-linked retinoschisis.
AB  - PURPOSE: To evaluate macular and extramacular retinal anatomy in patients and
      carriers of X-linked retinoschisis (XLRS) using a wide-field spectral-domain
      optical coherence tomography (SD-OCT) imaging technique. DESIGN: Case series.
      PARTICIPANTS: Six XLRS-affected male subjects and 3 XLRS female carriers.
      METHODS: The subjects prospectively underwent XLRS DNA genotyping and
      comprehensive ophthalmic examination, including visual acuity, 30-2 Humphrey
      visual field, fundus photography, and wide-field SD-OCT, a montage technique to
      generate SD-OCT images spanning approximately 50 degrees horizontally and 35
      degrees vertically of the posterior pole. MAIN OUTCOME MEASURES: Distribution and
      location of schisis cavities. RESULTS: Among male subjects affected by XLRS,
      asymmetric bilateral schisis was seen in all eyes imaged with montage SD-OCT (11
      eyes). Wide-field OCT images demonstrated schisis cavities only in the central
      macula in 6 eyes (55%), throughout the macula extending to the outside of the
      temporal arcades in 3 eyes (27%), and throughout the macula extending nasal to
      the optic nerve in 2 eyes (18%). Cystoid spaces accounting for macular splitting
      were present in the inner nuclear layer (INL) in all 11 eyes and in the outer
      nuclear layer (ONL) in 4 eyes. A few small cysts were seen parafoveally in the
      ganglion cell layer (GCL) or nerve fiber layer (NFL) in 4 eyes. Subclinical
      extramacular schisis spaces were seen (n=5 eyes) within the INL in 1 eye, the ONL
      in 1 eye, the INL/GCL/NFL in 1 eye, the ONL/GCL/NFL in 1 eye, and the
      INL/ONL/GCL/NFL in 1 eye. Schisis was rarely seen nasal to the optic nerve (2
      eyes). Central/paracentral visual field defects were seen in 9 eyes. Female
      carriers did not show schisis on examination or OCT. CONCLUSIONS: Wide-field SD
      OCT is a useful tool for evaluating complex retinal anatomy. In patients with
      XLRS, the foveomacular schisis was seen most frequently in the INL. Subclinical
      extramacular schisis was seen in 45% of eyes and was equally prevalent in the
      INL, ONL, and GCL/FNL. The GCL/FNL cystoid spaces were small and seen near the
      fovea and the arcades only. Carriers were schisis-free. FINANCIAL DISCLOSURE(S):
      The author(s) have no proprietary or commercial interest in any materials
      discussed in this article.

PMID- 23009890
TI  - Rotational autokeratoplasty in pediatric patients for nonprogressive paracentral
      corneal scars.
AB  - OBJECTIVE: To report the outcomes of ipsilateral rotational autokeratoplasty
      (RAK) for nonprogressive paracentral corneal opacities in children <16 years of
      age. DESIGN: Retrospective, consecutive, interventional case series.
      PARTICIPANTS: Thirty-three eyes of 33 children aged <16 years undergoing RAK for
      nonprogressive paracentral scars. METHODS: Medical records were retrospectively
      reviewed for the primary etiology of corneal opacity, time of onset, duration of
      opacity, preoperative visual acuity, formula used for calculation of trephine
      size, size of the trephine used, and duration of follow-up. Any intraoperative
      and early and late postoperative complications were noted for all patients.
      Postoperative visual acuity and astigmatism were noted. Visual acuity was
      converted to logarithm of the minimum angle of resolution units for analysis.
      MAIN OUTCOME MEASURES: Primary outcome was postoperative visual acuity. Graft
      clarity and complications were analyzed as secondary outcomes. RESULTS: The mean
      age at surgery was 7.2 +/- 3 .9 months. The mean follow-up duration was 27 +/- 37
      months. The commonest etiology of corneal opacity was trauma (62.5%), followed by
      resolved microbial keratitis (21.9%). Postoperative visual acuity (1.25 +/- 0.84)
      was significantly better (P<0.001) than preoperative visual acuity (2.05 +/-
      0.96). The mean astigmatism at last visit was 4.04 +/- 2.21 diopters.
      Postoperative visual acuity was better in older children (beta = -0.01; P = 0.03)
      and had a shorter delay in presentation (beta = 0.02; P = 0.05). At the last
      follow-up, the graft was clear in 27 cases (81.25%). The cumulative probability
      of graft survival was 85% at 2 years and 65% at 5 years. Complications included
      wound leak in 4 eyes, secondary glaucoma in 2 eyes, graft infiltrate and
      traumatic dehiscence in 1 eye each. CONCLUSIONS: Rotational is a autokeratoplasty
      viable alternative surgical option to allogenic keratoplasty. Graft survival at 2
      years seems to be better than allogenic keratoplasty. Younger age and delay in
      presentation contribute to poorer visual outcomes after surgery. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 23009891
TI  - Driving ability reported by neovascular age-related macular degeneration patients
      after treatment with ranibizumab.
AB  - OBJECTIVES: To determine the impact of ranibizumab on driving status, driving
      ability perception, and having 20/40 vision or better in patients with choroidal
      neovascularization resulting from age-related macular degeneration (AMD). DESIGN:
      Phase III, multicenter, randomized clinical trials (Minimally Classic/Occult
      Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age
      Related Macular Degeneration [MARINA] and Anti-VEGF Antibody for the Treatment of
      Predominantly Classic Choroidal Neovascularization in Age-Related Macular
      Degeneration [ANCHOR]). PARTICIPANTS: One thousand one hundred twenty-six
      patients with choroidal neovascularization resulting from AMD. METHODS:
      Participants were assigned randomly to sham (n=238), 0.3-mg ranibizumab monthly
      injections (n=238), or 0.5-mg ranibizumab monthly injections (n=240) for 24
      months (MARINA), or were randomized to verteporfin photodynamic therapy (PDT;
      n=143), 0.3-mg ranibizumab monthly injections (n=140), or 0.5-mg ranibizumab
      monthly injections (n=140) for 24 months (ANCHOR). MAIN OUTCOME MEASURES: Self
      reported driving status and driving ability perception were assessed as
      exploratory outcomes at baseline through 24 months after baseline using the 25
      item National Eye Institute Visual Function Questionnaire. Best-corrected visual
      acuity in each eye was assessed monthly through 24 months. RESULTS: At baseline,
      68.6% of patients in the MARINA trial and 62.7% of patients in the ANCHOR trial
      reported driving. Among patients driving at baseline in the MARINA trial 2 years
      after randomization, 67.2% (95% confidence interval [CI], 59.2-75.2) of sham
      patients and 78.4% (95% CI, 71.8-85.0) of 0.5-mg patients reported that they were
      still driving. Among patients driving at baseline in the ANCHOR trial at 2 years
      after randomization, 71.6% (95% CI, 60.8-82.4) of PDT patients and 91.4% (95% CI,
      85.3-97.5) of 0.5-mg patients were still driving. Also in the ANCHOR trial,
      ranibizumab-treated patients who were not driving at baseline seemed more likely
      to drive by months 12 and 24 than PDT patients. Perception of driving ability was
      correlated with improvement in visual acuity (VA) in the better-seeing eye at 12
      and 24 months (R2=0.17 and R2=0.20 at 12 and 24 months, respectively [P<0.001],
      in the MARINA trial; R2=0.13 and R2=0.14, respectively [P<0.001], in the ANCHOR
      trial). Visual acuity in one or both eyes 2 years after randomization was more
      likely to be 20/40 or better in the ranibizumab-treated groups. CONCLUSIONS:
      These results suggest that patients with neovascular AMD treated with ranibizumab
      are more likely to report driving ability and have vision of at least 20/40 than
      patients given sham treatment or PDT. FINANCIAL DISCLOSURE(S): Proprietary or
      commercial disclosure may be found after the references.

PMID- 23009892
TI  - Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked,
      multicenter, placebo-controlled phase II study.
AB  - OBJECTIVE: To investigate the dose response for efficacy of 1% and 2% rebamipide
      ophthalmic suspension compared with placebo in patients with dry eye. DESIGN: A
      randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose
      response phase II study. PARTICIPANTS: A total of 308 patients with dry eye.
      METHODS: After a 2-week screening period, patients were randomized to receive
      placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4
      times daily for 4 weeks. MAIN OUTCOME MEASURES: The primary objective end point
      was change in fluorescein corneal staining (FCS) score from baseline to last
      observation carried forward (LOCF). Secondary objective end points were lissamine
      green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the
      Schirmer's test. Secondary subjective end points included dry eye-related ocular
      symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred
      vision) score and patients' overall treatment impression score. RESULTS:
      Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and
      2% rebamipide were significantly more effective than the placebo in terms of the
      change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no
      significant difference between the rebamipide and placebo groups from baseline to
      LOCF in Schirmer's test values, and dose response was not observed. In the
      predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean
      change from baseline in the 2% rebamipide group was larger than that in the 1%
      rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular
      symptom scores and patients' overall treatment impression showed significant
      improvements in the 1% and 2% rebamipide groups compared with the placebo group,
      except for photophobia in the 1% rebamipide group. No deaths or drug-related
      serious adverse events occurred in any treatment group. The incidence of ocular
      abnormalities was similar across the rebamipide and placebo groups. CONCLUSIONS:
      Rebamipide was effective in treating both objective signs and subjective symptoms
      of dry eye and were well tolerated in this 4-week study. Although 1% and 2%
      rebamipide were both efficacious, 2% rebamipide may be more effective than 1%
      rebamipide in some measures. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 23009894
TI  - Retinal vascular geometry and glaucoma: the Singapore Malay Eye Study.
AB  - PURPOSE: To determine the associations of geometric measurements (tortuosity,
      branching angle, and fractal dimension) of retinal vessels with glaucoma. DESIGN:
      Population-based, cross-sectional study. PARTICIPANTS: Persons aged 40 to 80
      years who participated in the Singapore Malay Eye Study (n=3280; 78.7% response
      rate). METHODS: Quantitative retinal vascular parameters (tortuosity, branching
      angle, and fractal dimension) were measured from digital retinal fundus
      photographs using a computer-assisted program following a standardized grading
      protocol. Glaucoma was diagnosed according to the International Society of
      Geographic and Epidemiological Ophthalmology classification system. MAIN OUTCOME
      MEASURES: The associations among retinal vascular parameters with glaucoma, the
      main glaucoma subtype primary open-angle glaucoma (POAG), and ocular hypertension
      (OHT). RESULTS: A total of 123 persons (4.4% of the 2789 participants) had
      glaucoma in the final analysis, 87 (70.7%) of whom were diagnosed with POAG.
      After adjusting for age, sex, body mass index, diabetes, hypertension, smoking,
      axial length, and intraocular pressure (IOP), decreased retinal arteriolar
      tortuosity (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.38-2.18,
      comparing lowest vs. highest quartiles), decreased retinal venular tortuosity
      (OR, 1.59; 95% CI, 1.29-1.97), and narrower retinal venular branching angle (OR,
      1.22; 95% CI, 1.00-1.48) were associated with glaucoma. Similar associations were
      found between these retinal vascular parameters and POAG. Decreased retinal
      vascular fractal dimension was associated with OHT (OR 1.37; 95% CI, 1.04-1.82).
      CONCLUSIONS: Certain features of retinal vascular geometry are associated with
      glaucomatous optic neuropathy independently of vascular risk factors and IOP.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 23009893
TI  - Genetic studies of age-related macular degeneration: lessons, challenges, and
      opportunities for disease management.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a common cause of visual
      impairment in individuals >55 years of age worldwide. The varying clinical
      phenotypes of AMD result from contributions of genetic, epigenetic, and
      nongenetic (environmental) factors. Genetic studies of AMD have come of age as a
      direct result of tremendous gains from the human genome project, genome-wide
      association studies, and identification of numerous susceptibility loci. These
      findings have implicated immune response, high-density lipoprotein cholesterol
      metabolism, extracellular matrix, and angiogenesis signaling pathways in disease
      pathophysiology. MAIN OUTCOME MEASURES: Herein, we address how the wealth of
      genetic findings in AMD is expected to impact the practice of medicine, providing
      opportunities for improved risk assessment, molecular diagnosis, preventive, and
      therapeutic intervention. CONCLUSIONS: We propose that the potential of using
      genetic variants for monitoring treatment response (pharmacogenetics) may usher
      in a new era of personalized medicine in the clinical management of AMD.
      FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after
      the references.

PMID- 23009895
TI  - Subfoveal choroidal thickness: the Beijing Eye Study.
AB  - PURPOSE: To study subfoveal choroidal thickness (SFCT) in adult Chinese subjects
      and its correlation with ocular biometric parameters, refractive error, and age.
      DESIGN: Population-based longitudinal study. PARTICIPANTS: The population-based
      Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6+/-9.8
      years (range, 50-93 years). METHODS: A detailed ophthalmic examination was
      performed, including spectral-domain optical coherence tomography (SD-OCT) with
      enhanced depth imaging for measurement of SFCT. MAIN OUTCOME MEASURES: Subfoveal
      choroidal thickness. RESULTS: The SFCT measurements were available for 3233
      subjects (93.2%). Mean SFCT was 253.8+/-107.4 MUm (range, 8-854 MUm). In
      multivariate analysis, SFCT increased with younger age (P<0.001; correlation
      coefficient r=4.12; beta coefficient=0.37), shorter axial length (P<0.001;
      r=44.7; beta coefficient=0.46), male gender (P<0.001; r=28.5; beta coefficient=
      0.13), deeper anterior chamber depth (P<0.001; r=39.3; beta coefficient=0.13),
      thicker lens (P<0.001; r=26.8; beta coefficient=0.08), flatter cornea (P<0.001;
      r=46.0; beta coefficient=0.11), and better best-corrected visual acuity (BCVA)
      (logarithm of minimal angle of resolution; P=0.001; r=48.4; beta
      coefficient=0.06). In multivariate analysis, SFCT was not significantly
      associated with blood pressure, ocular perfusion pressure, intraocular pressure,
      cigarette smoking, alcohol consumption, serum concentrations of lipids and
      glucose, diabetes mellitus, and arterial hypertension. In the myopic refractive
      error range of more than -1 diopter (D), SFCT decreased by 15 MUm (95% confidence
      interval [CI], 11.9-18.5) for every increase in myopic refractive error of 1 D,
      or by 32 MUm (95% CI, 37.1-26.0) for every increase in axial length of 1 mm. For
      each year increase in age, the SFCT decreased by 4.1 MUm (95% CI, 4.6-3.7)
      (multivariate analysis). CONCLUSIONS: Subfoveal choroidal thickness with a mean
      of 254+/-107 MUm in elderly subjects with a mean age of 65 years decreased with
      age (4 MUm per year of age) and myopia (15 MUm per diopter [D] of myopia). It was
      also associated with male gender and the ocular biometric parameters of a deeper
      anterior chamber and thicker lens. The association between SFCT and BCVA
      indicates a functional aspect of SFCT. FINANCIAL DISCLOSURE(S): The author(s)
      have no proprietary or commercial interest in any materials discussed in this
      article.

PMID- 23009896
TI  - Transesterification catalyzed by ionic liquids on superhydrophobic mesoporous
      polymers: heterogeneous catalysts that are faster than homogeneous catalysts.
AB  - Homogeneous catalysts usually show higher catalytic activities than heterogeneous
      catalysts because of their high dispersion of catalytically active sites. We
      demonstrate here that heterogeneous catalysts of ionic liquids functionalized on
      superhydrophobic mesoporous polymers exhibit much higher activities in
      transesterification to form biodiesel than homogeneous catalysts of the ionic
      liquids themselves. This phenomenon is strongly related to the unique features of
      high enrichment and good miscibility of the superhydrophobic mesoporous polymers
      for the reactants. These features should allow the design and development of a
      wide variety of catalysts for the conversion of organic compounds.

PMID- 23009898
TI  - The power of longitudinal population-based studies for investigating the etiology
      of chronic widespread pain.

PMID- 23009900
TI  - [Perirenal abscess and ureteral foreign body].

PMID- 23009899
TI  - Distinct spatiotemporal roles of hedgehog signalling during chick and mouse
      cranial base and axial skeleton development.
AB  - The cranial base exerts a supportive role for the brain and includes the
      occipital, sphenoid and ethmoid bones that arise from cartilaginous precursors in
      the early embryo. As the occipital bone and the posterior part of the sphenoid
      are mesoderm derivatives that arise in close proximity to the notochord and floor
      plate, it has been assumed that their development, like the axial skeleton, is
      dependent on Sonic hedgehog (Shh) and modulation of bone morphogenetic protein
      (Bmp) signalling. Here we examined the development of the cranial base in chick
      and mouse embryos to compare the molecular signals that are required for
      chondrogenic induction in the trunk and head. We found that Shh signalling is
      required but the molecular network controlling cranial base development is
      distinct from that in the trunk. In the absence of Shh, the presumptive cranial
      base did not undergo chondrogenic commitment as determined by the loss of Sox9
      expression and there was a decrease in cell survival. In contrast, induction of
      the otic capsule occurred normally demonstrating that induction of the cranial
      base is uncoupled from formation of the sensory capsules. Lastly, we found that
      the early cranial mesoderm is refractory to Shh signalling, likely accounting for
      why development of the cranial base occurs after the axial skeleton. Our data
      reveal that cranial and axial skeletal induction is controlled by conserved, yet
      spatiotemporally distinct mechanisms that co-ordinate development of the cranial
      base with that of the cranial musculature and the pharyngeal arches.

PMID- 23009901
TI  - [Utility of diffusion-weighted magnetic resonance imaging in severe focal
      traumatic brain injuries].
AB  - OBJECTIVE: To describe the apparent diffusion coefficient (ADC) in a series of
      severe traumatic brain injuries, their clinical and outcome features, and
      possible implications. DESIGN: A descriptive, observational case-series study was
      carried out. PATIENTS AND INTERVENTIONS: Patients with severe traumatic brain
      injuries (TBIs) admitted to the ICU were subjected to MRI study using a 1.5 T
      scanner. Diffusion-weighted images (DWMR) were obtained using the following echo
      planar pulse sequence: TR 10000 ms, TE 126.9 ms, with b values 1000 s/mm2 in the
      three spatial dimensions. Combining the three sets of images, an isotropic image
      conforming a map of the mean ADCs was obtained. RESULTS: DWMR was performed in 23
      patients with severe TBI admitted to the ICU between 2001 and 2004. In the MR
      images we selected 26 regions of interest (ROIs) where ADC was recorded. We
      observed a clear increase in diffusion in non-treated space-occupying lesions
      versus other types of injuries and the normal values. A poorer outcome was
      recorded in patients with lower ADC values. CONCLUSIONS: Mean ADC in the lesions
      was greater than the normal values and greater in contusions than in other types
      of injuries, as an expression of extracellular edema. ADCs were decreased in
      patients with a poor outcome, suggesting an association between ischemia and the
      patient prognosis.

PMID- 23009902
TI  - [Hospitalists as a work force in intensive care in the United States and Latin
      America?].

PMID- 23009903
TI  - A polymorphism in the leptin receptor gene at position 223 is associated with
      growth hormone replacement therapy responsiveness in idiopathic short stature and
      growth hormone deficiency patients.
AB  - We hypothesized that responses to growth hormone (GH) therapy by idiopathic short
      stature (ISS) and growth hormone deficiency (GHD) patients were associated with
      single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor
      (LEPR) genes. We retrospectively enrolled ISS (n = 32) and GHD (n = 38) patients
      and forty healthy age-and gender-matched children. They were genotyped for the
      LEP promoter at nt.-2548, and LEPR K109R and LEPR Q223R polymorphisms. Clinical
      and laboratory variables were determined before and after 2 years of GH
      treatment. ISS patients with G/A or A/A genotypes of the LEPR Q223R SNP had a
      significantly higher height velocity (cm/y) than ISS patients with the G/G
      genotype at 2 years after GH treatment. For GHD patients, G/A or A/A genotype of
      the LEPR K109R SNP was associated with higher body weight, higher BMI, and higher
      weight velocity than patients with the G/G genotype before GH treatment, but not
      after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with
      a significantly higher body weight, higher height velocity before treatment, but
      not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated
      with a significantly higher weight velocity before treatment, but a significantly
      lower weight velocity was found at 2 years after GH treatment. These results
      suggest LEPR Q223R SNP (rs1137101) is associated with outcomes of GH replacement
      therapy in ISS and GHD patients.

PMID- 23009904
TI  - Estimating infectivity rates and attack windows for two viruses.
AB  - Cells exist in an environment in which they are simultaneously exposed to a
      number of viral challenges. In some cases, infection by one virus may preclude
      infection by other viruses. Under the assumption of independent times until
      infection by two viruses, a procedure is presented to estimate the infectivity
      rates along with the time window during which a cell might be susceptible to
      infection by multiple viruses. A test for equal infectivity rates is proposed and
      interval estimates of parameters are derived. Additional hypothesis tests of
      potential interest are also presented. The operating characteristics of these
      tests and the estimation procedure are explored in simulation studies.

PMID- 23009905
TI  - Pulmonary vascular disease and the right ventricle. Introduction.

PMID- 23009906
TI  - WHO Group 1 pulmonary arterial hypertension: current and investigative therapies.
AB  - Major advances have been made in the treatment of World Health Organization Group
      1 pulmonary arterial hypertension (PAH). Since the mid-1990s, nine medications
      have become available in the United States to target three key pathophysiologic
      derangements in PAH - the prostacyclin, endothelin, and nitric oxide pathways. As
      a group, these agents have led to improvements in functional capacity, symptoms,
      hemodynamics, and survival. Most patients with mild to moderate PAH are started
      on orally active agents such as endothelin receptor antagonists or
      phosphodiesterase inhibitors. Patients with more severe disease, particularly
      those with evidence of right heart failure, should be treated with continuous
      prostacyclin infusion or a combination of a prostacyclin and oral therapy. Each
      medication has unique properties and clinical considerations, and the selection
      of an appropriate therapy must be tailored to the individual patient. None of the
      currently available WHO Group 1 PAH therapies are curative, however, and it is
      the hope that new therapies in development may halt or reverse disease
      progression. This review will discuss the major therapeutic classes of presently
      available medications and their role in managing the patient with PAH. We will
      also review data supporting the use of combination therapy, adjuvant background
      therapy, and new agents currently under investigation.

PMID- 23009907
TI  - Pulmonary hypertension and right ventricular dysfunction in left heart disease
      (group 2 pulmonary hypertension).
AB  - Group 2 pulmonary hypertension is most frequently caused by left heart disease, a
      heterogeneous set of disorders. These processes include left ventricular systolic
      dysfunction, left ventricular dysfunction with preserved ejection fraction and
      valvular (mitral and/or aortic) diseases. Left heart disease may cause passive
      backward transmission of pressure leading to elevated left atrial and pulmonary
      arterial pressures due to a myriad of processes. Increasingly, it has been
      recognized that some patients may develop pulmonary arterial pressure out of
      proportion from what is expected. This is believed to be due to increases in
      vasomotor tone and/or vascular remodeling. Over time patients may go on to
      develop progressive right ventricular dysfunction, a marker for poor prognosis.
      This review will explore the different characteristics of these conditions
      including the incidence, pathophysiology, clinical implications, prognosis and
      current state of available medical therapies.

PMID- 23009908
TI  - World Health Organization Group III pulmonary hypertension.
AB  - Pulmonary hypertension in the setting of parenchymal lung disease and conditions
      associated with chronic hypoxemia is commonly encountered in clinical practice
      and may adversely affect patients' function and mortality. Diagnosis of this
      subgroup of pulmonary hypertension has evolved but still requires right heart
      catheterization for confirmation. The primary treatment goal is optimization of
      the underlying parenchymal lung or hypoxemia-associated condition prior to
      consideration of pharmacologic therapy. Limited published experience with
      pulmonary hypertension-specific medications for treatment of WHO Group 3
      pulmonary hypertension suggests symptomatic and functional benefit in selected
      individuals. The potential for worsening ventilation-perfusion matching must be
      considered in these cases, however, since there is a paucity of data regarding
      the optimal approach to treatment selection. Ongoing medication trials and
      further investigation of mechanisms of hypoxic pulmonary vasoconstriction provide
      hope for these patients who in the past often had only lung transplantation as a
      potential treatment option.

PMID- 23009909
TI  - Congenital heart disease and pulmonary hypertension: pharmacology and feasibility
      of late surgery.
AB  - Pulmonary arterial hypertension (PAH) with increased pulmonary vascular
      resistance (PVR), previously termed pulmonary vascular obstructive disease or
      pulmonary vascular disease is a frequent complication of congenital heart disease
      (CHD).While there have been advances in the medical treatments available for
      classic Eisenmenger syndrome patients who are not suitable for repair, the sub
      group of patients with moderate sized congenital systemic to pulmonary shunts and
      mild to moderately elevated PVR remains challenging. With the development of
      targeted medical treatments for pulmonary arterial hypertension (PAH), the
      concept of a combined medical and interventional/surgical approach for patients
      with PAH associated with CHD (APAH-CHD) has emerged. Careful evaluation and an
      understanding of the predominant physiologic features will help guide the
      management of these complex patients and whether late surgical repair is
      feasible.

PMID- 23009910
TI  - Chronic thromboembolic pulmonary hypertension: a review of current practice.
AB  - Pulmonary artery hypertension is a complex and multi-faceted disease process with
      numerous etiologies. Chronic thromboembolic pulmonary hypertension (CTEPH) is an
      underdiagnosed and highly treatable form of pulmonary hypertension. In this
      disease, certain patients with a history of pulmonary thromboembolic disease go
      on to develop elevated pulmonary artery pressures, shortness of breath, and
      progressive right heart failure. This article will review the epidemiology,
      pathophysiology, diagnosis and treatment of CTEPH with a review of pulmonary
      thromboendarterectomy surgery.

PMID- 23009911
TI  - Echocardiographic assessment of the right ventricle and associated hemodynamics.
AB  - Echocardiographic imaging of the right ventricle has inherent challenges stemming
      from the chamber's complex shape. More focus has been placed on right ventricular
      function recently because it is an independent prognostic indicator of morbidity
      and mortality in heart failure and pulmonary hypertension. Echocardiography is a
      widely available, inexpensive, and well-validated tool that allows for
      comprehensive evaluation of the right ventricle's size and function. With
      improvements in ultrasound techniques and methods, there are many qualitative and
      quantitative indices that, when used in conjunction with noninvasive pulmonary
      hemodynamics, provide important diagnostic and prognostic information to the
      clinician. As echocardiographic modalities - particularly three-dimensional
      imaging - improve, enhanced assessment of the right ventricle will lead to a
      better understanding of the pathophysiology of right heart failure and enhanced
      ability to follow responses to therapy.

PMID- 23009912
TI  - Computed tomography and cardiac magnetic resonance imaging in pulmonary
      hypertension.
AB  - Recent advances in imaging technology have allowed for better temporal and
      spatial resolution in cardiovascular imaging. The idea of a "one-stop shop" for
      anatomical and functional cardiopulmonary and vascular assessment in patients
      with pulmonary hypertension is very appealing since diagnostic, prognostic, and
      therapeutic response can be measured. Modalities, such as computed tomography
      (CT) and cardiac magnetic resonance (CMR), are better suited to image the right
      heart and associated structures in multiple projections allowing for three
      dimensional data sets and image reconstruction. This review will focus on the use
      of CT and CMR in the assessment of the right ventricle and pulmonary structures
      as they relate to pulmonary vascular disease.

PMID- 23009913
TI  - Exercise physiology and pulmonary arterial hypertension.
AB  - The lungs are the only organ that receives the entire cardiac output with every
      stroke. The pulmonary circulation is normally a high-flow, low-resistance, low
      pressure system that carries blood into the pulmonary microcirculation. In
      pulmonary artery hypertension (PAH)vascular remodeling contributes to a sustained
      elevation of pulmonary vascular resistance (PVR) and pulmonary artery pressure
      (PAP) as a result of vascular remodeling characterized largely by vascular smooth
      muscle cell proliferation and medial hypertrophy, and endothelial cell
      proliferation resulting in lumen obliteration. The loss of pulmonary arterial
      compliance and development of elevated PVR puts an excessive burden on the right
      ventricle due to the increased workload necessary to overcome the downstream
      pressure, ultimately leading to right-sided heart failure. The functional status
      of the pulmonary circulation and the levels of PVR and PAP ultimately determine
      the outcome of patients with PAH. Study of the pressure-flow relationships in the
      pulmonary vascular bed will provide an improved appreciation of the
      pathophysiology of pulmonary hypertension.

PMID- 23009915
TI  - Pulmonary hypertension in the intensive care unit.
AB  - Pulmonary hypertension, a condition that can lead to right ventricular failure
      and hemodynamic collapse, can be very challenging to manage in critically ill
      patients who require the intensive care unit. Because of the underlying structure
      of the right ventricle, significant increases in right ventricular afterload
      initiate a vicious cycle of degenerating right ventricular function, giving rise
      to right ventricular failure and cardiogenic shock. In patients with pulmonary
      hypertension, inciting factors such as sepsis and arrhythmias can exacerbate this
      process. Important management principles include close monitoring of hemodynamics
      with both noninvasive and invasive modalities, optimization of right ventricular
      preload, maintenance of systemic blood pressure, enhancement of right ventricular
      contractility, reduction of right ventricular afterload, and reversal of
      identifiable inciting factors. The goal of this review is to discuss these key
      concepts in managing this difficult patient population.

PMID- 23009914
TI  - Arrhythmias in pulmonary arterial hypertension.
AB  - Cardiac arrhythmias are important contributors to morbidity and mortality in
      patients with pulmonary arterial hypertension (PAH). Such patients manifest a
      substrate resulting from altered autonomics, repolarization abnormalities, and
      ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter
      are associated with worsened outcomes, and maintenance of sinus rhythm is a goal.
      Sudden death is a relatively common issue, though the contribution of malignant
      ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients.
      Congenital heart disease patients with PAH benefit from catheter ablation of
      medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker
      therapy for primary prevention against sudden death in PAH patients are lacking.

PMID- 23009916
TI  - Anesthesia and pulmonary hypertension.
AB  - Anesthesia and surgery are associated with significantly increased morbidity and
      mortality in patients with pulmonary hypertension due mainly to right ventricular
      failure, arrhythmias, postoperative hypoxemia, and myocardial ischemia.
      Preoperative risk assessment and successful management of patients with pulmonary
      hypertension undergoing cardiac surgery involve an understanding of the
      pathophysiology of the disease, screening of patients at-risk for pulmonary
      arterial hypertension, analysis of preoperative and operative risk factors,
      thorough multidisciplinary planning, careful intraoperative management, and early
      recognition and treatment of postoperative complications. This article will cover
      each of these aspects with particular focus on the anesthetic approach for non
      cardiothoracic surgeries.

PMID- 23009919
TI  - Right ventricular assist device in end-stage pulmonary arterial hypertension:
      insights from a computational model of the cardiovascular system.
AB  - BACKGROUND: The high mortality rate of pulmonary arterial hypertension (PAH)
      mainly relates to progressive right ventricular (RV) failure. With limited
      efficacy of medical therapies, mechanical circulatory support for the RV has been
      considered. However, there is lack of understanding of the hemodynamic effects of
      mechanical support in this setting. METHODS: We modeled the cardiovascular
      system, simulated cases of PAH and RV dysfunction and assessed the theoretical
      effects of a continuous flow micro-pump as an RV assist device (RVAD). RVAD
      inflow was sourced either from the RV or RA and outflow was to the pulmonary
      artery. RVAD support was set at various flow rates and additional simulations
      were carried out in the presence of atrial septostomy (ASD) and tricuspid
      regurgitation (TR). RESULTS: RVAD support increased LV filling, thus improving
      cardiac output and arterial pressure, unloading the RA and RV, while raising
      pulmonary arterial and capillary pressures in an RVAD flow-dependent manner.
      These effects diminished with increasing disease severity. The presence of TR did
      not significantly impact the hemodynamic effects of RVAD support. ASD reduced the
      efficacy of RVAD support, since right-to-left shunting decreased and ultimately
      reversed with increasing RVAD support due to the progressive drop in RA pressure.
      CONCLUSIONS: The results of this theoretical analysis suggest that RVAD support
      can effectively increase cardiac output and decreases RA pressure with the
      consequence of increasing pulmonary artery and capillary pressures. Especially in
      advanced PAH, low RVAD flow rates may mitigate these potentially detrimental
      effects while effectively increasing systemic hemodynamics.

PMID- 23009917
TI  - Immune and inflammatory mechanisms in pulmonary arterial hypertension.
AB  - Altered immunity and inflammation are increasingly recognized features of
      pulmonary arterial hypertension (PAH). This is suggested by infiltration of
      various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased
      cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled
      pulmonary vessels, and the presence of circulating chemokines and cytokines. In
      certain diseases associated with PAH, increased expression of growth and
      transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors, and
      viral protein components (e.g., HIV-1 Nef), appear to contribute directly to
      recruitment of inflammatory cells in remodeled vessels, and may potentially serve
      as specific therapeutic targets. This section provides an overview of
      inflammatory pathways highlighting their potential role in pulmonary vascular
      remodeling in PAH and the possibility of future targeted therapy.

PMID- 23009918
TI  - Metabolism of the right ventricle and the response to hypertrophy and failure.
AB  - Profound transcriptional, translational and energetic derangements develop in the
      right ventricle (RV) in response to physiologic and pathophysiologic stress. The
      transition from pressure and volume overload to cardiac hypertrophy and
      subsequent failure is accompanied by a distinct switch from preferential fatty
      acid to glucose utilization for ATP generation. The failing RV is characterized
      by an energy-starved state with insufficient ATP levels. Modern non-invasive
      imaging using positron emission tomography using specific radioactive tracers
      allows a detailed spatial and temporal characterization of RV metabolism. While
      the current role for pharmacologic interventions on RV metabolic abnormalities is
      unclear, several potentially promising molecular targets have been identified and
      clinical trials targeting molecular dysfunction in RV hypertrophy and failure
      have been designed.

PMID- 23009920
TI  - Antibodies recognizing both IgM isotypes in Atlantic salmon.
AB  - Identification and characterization of subpopulations of cells involved in
      immunological reactions against invading organisms are essential for
      understanding defense mechanisms against disease. In lower vertebrates like
      teleost fish, as opposed to mammals, immune cell subsets are still poorly
      defined, mostly due to the lack of appropriate working tools like antibodies and
      functional assays. Membrane bound molecules like immunoglobulins (Ig) serve as
      cell surface markers for specific cell subsets and the identification of cells
      relies upon the production of specific antibodies towards these molecules. The
      present study aimed at identifying tools to separate IgM positive (IgM(+)) B
      cells from IgM negative (IgM(-)) non-B cell populations using flow cytometry.
      Several monoclonal antibodies (mAbs), and one polyclonal antibody (pAb) to both
      rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) IgM, either
      commercially available or locally produced were tested for their recognition of
      Atlantic salmon IgM(+) cells. Leukocytes were isolated from peripheral blood
      (PB), spleen (S) and head kidney (HK) and stained with all mAbs and the pAb, to
      possibly verify the approximate number of IgM(+) cells in the respective tissues
      in salmon. To our surprise, this seemingly simple task did not reveal similar
      staining patterns for all antibodies as expected, but rather large differences in
      the number of positively stained cells were discovered. In short, positively
      stained cells by each antibody ranged from below 5% to above 80% with similar
      ratios between the antibodies in each tissue. The three most used mAbs, 4c10, N2
      and 1.14; originally produced towards rainbow trout IgM, recognize only a
      fraction of salmon B cells as previously shown for the 4c10 mAb binding
      exclusively to the IgM-A isotype. In comparison, our three novel mAbs, IgF1-3, 
      18 and -19, bind to both IgM-A and -B isotypes as shown using intracellular
      staining of 293T cells transfected with both IgM-A and -B constructs. Based on
      binding percentages, one of three commercially available Abs, IgH FITC from
      Cedarlane, may also identify both isotypes. The three new IgF1-3, -18 and -19
      mAbs and potentially IgH FITC from Cedarlane, provide us with great tools
      enabling complete depletion or enrichment of IgM(+) B cells and/or IgM(-) T cells
      in Atlantic salmon.

PMID- 23009921
TI  - Molecular cloning, characterization and expression of cathepsin D from grass carp
      (Ctenopharyngodon idella).
AB  - Cathepsin D is a lysosomal aspartic proteinase which participates in various
      degradation functions within the cell. In this current study, we cloned and
      characterized the complete cDNA of grass carp cathepsin D through 5'- and 3'
      RACE. The cathepsin D contained a 56 bp 5' terminal untranslated region (5'-UTR),
      a 1197 bp open reading frame encoding 398 amino acids, and a 394 bp 3'-UTR. Grass
      carp cathepsin D shared high similarity with those from other species, and showed
      the highest amino acid identity of 91% to Danio rerio. Unlike many other
      organisms, the grass carp cathepsin D contains only one N-glycosylation site
      closest to the N-terminal. Real-time quantitative RT-PCR demonstrated that
      Cathepsin D expressed in all twelve tissues (bladder, brain, liver, heart, gill,
      muscle, fin, eye, intestines, spleen, gonad and head kidney). The relative
      expression levels of Cathepsin D in gonad and liver were 26.58 and 24.95 times as
      much as those in fin, respectively. The expression level of Cathepsin D in muscle
      approximately 16-fold higher, in intestines and spleen were 12-fold higher. The
      cathepsin D expression showed an upward trend during embryonic development. After
      challenged with Aeromonas hydrophil, the expression of grass carp cathepsin D
      gene showed significant changes in the four test tissues (liver, head kidney,
      spleen and intestines). The fact that the bacterial infection can obviously
      improve the cathepsin D expression in immune-related organs, may suggest that
      cathepsin D plays an important role in the innate immune response of grass carp.

PMID- 23009922
TI  - [Radiology and the butterfly effect].

PMID- 23009923
TI  - Cost comparison between private and public collection of residual household
      waste: multiple case studies in the Flemish region of Belgium.
AB  - The rising pressure in terms of cost efficiency on public services pushes
      governments to transfer part of those services to the private sector. A trend
      towards more privatizing can be noticed in the collection of municipal household
      waste. This paper reports the findings of a research project aiming to compare
      the cost between the service of private and public collection of residual
      household waste. Multiple case studies of municipalities about the Flemish region
      of Belgium were conducted. Data concerning the year 2009 were gathered through in
      depth interviews in 2010. In total 12 municipalities were investigated, divided
      into three mutual comparable pairs with a weekly and three mutual comparable
      pairs with a fortnightly residual waste collection. The results give a rough
      indication that in all cases the cost of private service is lower than public
      service in the collection of household waste. Albeit that there is an interest in
      establishing whether there are differences in the costs and service levels
      between public and private waste collection services, there are clear
      difficulties in establishing comparisons that can be made without having to rely
      on a large number of assumptions and corrections. However, given the cost
      difference, it remains the responsibility of the municipalities to decide upon
      the service they offer their citizens, regardless the cost efficiency: public or
      private.

PMID- 23009924
TI  - The value of composting in Germany--economy, ecology, and legislation.
AB  - Based on a recent survey of German composting plants an evaluation of costs and
      benefits of composting was attempted. In this regard, several economical,
      ecological and legal aspects and some interrelations are discussed in this paper.
      A special emphasis is placed on the fees and compost prices of composting plants.
      It is also shown how the legal framework provides the economic basis for
      composting in Germany, how economical and ecological costs and benefits could be
      assessed, and why it is so difficult to determine the value of composting.

PMID- 23009925
TI  - Deepening TOL and TOU catabolic pathways of Pseudomonas sp. OX1: cloning,
      sequencing and characterization of the lower pathways.
AB  - Pseudomonas sp. OX1 is able to metabolize toluene and o-xylene through the TOU
      catabolic pathway, whereas its mutant M1 strain was found to be able to use m-
      and p-xylene as carbon and energy source, using the TOL catabolic pathway. Here
      we report the complete nucleotide sequence of the phe lower operon of the TOU
      catabolic pathway, and the sequence of the last four genes of the xyl-like lower
      operon of the TOL catabolic pathway. DNA sequence analysis shows the gene order
      within the operons to be pheCDEFGHI (phe operon) and xyl-likeQKIH (xyl-like
      operon), identical to the order found for the isofunctional genes of meta operons
      in the toluene/xylene pathway of TOL plasmid pWW0 from Pseudomonas putida mt-2
      and the phenol/methylphenol pathway of pVIl50 from Pseudomonas sp. CF600. The
      nucleotide and the deduced amino acid sequences are homologous to the equivalent
      gene and enzyme sequences from other Pseudomonas meta pathways. Recombinant 2
      hydroxymuconic semialdehyde dehydrogenase (HMSD) and 2-hydroxymuconic
      semialdehyde hydrolase (HMSH), coded by pheCD genes, respectively, and ADA and
      HOA enzymes from both phe and xyl operons were expressed in E. coli and steady
      state kinetic analysis was carried out. The analysis of the kinetic parameters of
      HMSD and HMSH showed that the enzymes from Pseudomonas sp. OX1 are more
      specialized to channel metabolites into the two branches of the lower pathway
      than homologous enzymes from other pseudomonads. The kinetics parameters of
      recombinant ADA from phe and xyl-like operon were found to be similar to those of
      homologous enzymes from other Pseudomonas strains. In addition, the enzyme from
      xyl-like operon showed a substrate affinity three times higher than the enzyme
      from phe operon.

PMID- 23009926
TI  - Plant sterol oxidation products--analogs to cholesterol oxidation products from
      plant origin?
AB  - Cholesterol and plant sterols are lipids which are abundantly present in a
      western type diet of animal and plant origin, respectively. The daily intake
      averages 300 mg/day each. Over the past decades, a steadily increasing
      consumption of plant sterol enriched dairy products (2-3 g/day) took place to
      lower circulating LDL cholesterol concentrations. Like all unsaturated
      components, plant sterols can be attacked by reactive oxygen species resulting in
      plant sterol oxidation products (POPs). The most widespread methods for POP
      determination are high-performance liquid chromatography and gas-liquid
      chromatography. Yet, based on the low plasma POP concentrations in
      normophytosterolemic subjects (POPs: ~0.3-4.5 ng/mL), a reliable quantification
      yielding an appropriate limit of detection remains a challenge. While the more
      abundantly present cholesterol oxidation products (COPs) have elaborately been
      studied, research on the metabolism and biological effects of POPs is only
      emerging. In relation to atherogenity, biological effects including modulation of
      cholesterol homeostasis, membrane functioning, and inflammation are attributed to
      POPs. Although mostly supra-physiological concentrations are applied in in vitro
      assays, anti-tumor activity, cytotoxicity and estrogen-competition have been
      attributed to specific POPs. However, it is not obvious, if and how POPs may
      exert in vivo adverse or beneficial health effects similar to those attributed to
      COPs. In the field of nutritional science, standardized methods for the
      determination of POPs are required to perform relevant biological studies and to
      assess their presence in complex foods or biological tissues and fluids. The aim
      of this review is to provide an overview and evaluation of the published methods
      and an update on the biological effects attributed to POPs.

PMID- 23009927
TI  - F(2)-Dihomo-isoprostanes and brain white matter damage in stage 1 Rett syndrome.
AB  - Oxidative damage has been reported in Rett syndrome (RTT), a pervasive
      development disorder mainly caused up to 95% of cases by mutations in the X
      linked methyl-CpG binding protein 2 (MeCP2) gene. We have recently synthesized
      F(2)-Dihomo-isoprostanes (F(2)-Dihomo-IsoP), peroxidation products from adrenic
      acid (C22:4 n - 6, AdA), a known component of myelin, and tested the potential
      value of F(2)-Dihomo-IsoPs as a novel disease marker and its relationship with
      clinical presentation, and disease progression. F(2)-Dihomo-IsoPs were determined
      by a gas chromatography/negative ion chemical ionization tandem mass
      spectrometry. The ent-7(RS)-F(2t)-Dihomo-IsoP and 17-F(2t)-Dihomo-IsoP were used
      as reference standards. The measured ions were the product ions at m/z 327
      derived from the [M - 181](-) precursor ions (m/z 597) produced from both the
      derivatized ent-7(RS)-F(2t)-Dihomo-IsoP and 17-F(2t)-Dihomo-IsoP. Average plasma
      F(2)-Dihomo-IsoP levels in RTT were about 1 order of magnitude higher than in
      healthy controls, being higher in typical RTT as compared to RTT variants, with a
      remarkable increase of about 2 orders of magnitude in patients at the earliest
      stage of the disease followed by a steady decrease during the natural clinical
      progression. These data indicate for the first time that quantification of F(2)
      Dihomo-IsoPs in plasma represents an early marker of the disease and may provide
      a better understanding of the pathogenic mechanisms behind the neurological
      regression in patients with RTT.

PMID- 23009928
TI  - The structural analysis and the role of calcium binding site for thermal
      stability in mannanase.
AB  - Mannanase is an important enzyme involved in the degradation of mannan,
      production of bioactive oligosaccharides, and biobleaching of kraft pulp.
      Mannanase must be thermostable for use in industrial applications. In a previous
      study, we found that the thermal stability of mannanase from Streptomyces
      thermolilacinus (StMan) and Thermobifida fusca (TfMan) is enhanced by calcium.
      Here, we investigated the relationship between the three-dimensional structure
      and primary sequence to identify the putative calcium-binding site. The results
      of site-directed mutagenesis experiments indicated that Asp-285, Glu-286, and Asp
      287 of StMan (StDEDAAAdC) and Asp-264, Glu-265, and Asp-266 of TfMan (TfDEDAAAdC)
      were the key residues for calcium binding affinity. Isothermal titration
      calorimetry revealed that the catalytic domain of StMan and TfMan (StMandC and
      TfMandC, respectively) bound calcium with a K(a) of 3.02 * 10(4) M(-1) and 1.52 *
      10(4) M(-1), respectively, both with stoichiometry consistent with one calcium
      binding site per molecule of enzyme. Non-calcium-binding mutants (StDEDAAAdC and
      TfDEDAAAdC) did not show any calorimetric change. From the primary structure
      alignment of several mannanases, the calcium-binding site was found to be highly
      conserved in GH5 bacterial mannanases. This is the first study indicating
      enhanced thermal stability of GH5 bacterial mannanases by calcium binding.

PMID- 23009929
TI  - A novel cell-penetrating peptide TAT-A1 delivers siRNA into tumor cells
      selectively.
AB  - siRNA is promising in anti-tumor therapy. The main challenge is lack of tumor
      specific intracellular delivery. In this study, a 6 amino acids peptide (A1) with
      high affinity for vascular endothelial growth factor receptor-1 (VEGFR1) was
      conjugated with a cell penetrating peptide (CPP) TAT to form a tumor-selective
      CPP. To evaluate the tumor-targeted penetrate property of TAT-A1, the uptake of
      TAT-A1 was measured by flow cytometry. The selectivity in vitro was tested in co
      cultured tumor cells and normal cells by laser confocal microscope. The
      internalization efficiency of TAT-A1 was significantly higher than that of TAT (p
      < 0.05). TAT-A1 penetrated into tumor cells selectively when added to co-cultured
      tumor cells and normal cells due to the recognition of VEGFR1 which is over
      expressed on tumor cells. Furthermore, siRNA was successfully transferred by TAT
      A1 into tumor cells in a similar way of Lipofectamine 2000, which was proved to
      be an efficient vector. The knockout effect of siRNA transferred by TAT-A1 was
      obtained at both mRNA and protein level. These results indicated that the tumor
      targeted TAT-A1 can act as an excellent vehicle for specific delivery of anti
      cancer agents.

PMID- 23009930
TI  - Modification of SR-PSOX functions by multi-point mutations of basic amino acid
      residues.
AB  - SR-PSOX can function as a scavenger receptor, a chemokine and an adhesion
      molecule, and it could be an interesting player in the formation of
      atherosclerotic lesions. Our previous studies demonstrated that basic amino acid
      residues in the chemokine domain of SR-PSOX are critical for its functions. In
      this study the combinations of the key basic amino acids in the chemokine domain
      of SR-PSOX have been identified. Five combinations of basic amino acid residues
      that may form conformational motif for SR-PSOX functions were selected for multi
      point mutants. The double mutants of K61AR62A, R76AK79A, R82AH85A, and treble
      mutants of R76AR78AK79A, R78AR82AH85A were successfully constructed by replacing
      the combinations of two or three basic amino acid residues with alanine. After
      successful expression of these mutants on the cells, the functional studies
      showed that the cells expressing R76AK79A and R82AH85A mutants significantly
      increased the activity of oxLDL uptake compared with that of wild-type SR-PSOX.
      Meanwhile, the cells expressing R76AK79A mutant also dramatically enhanced the
      phagocytotic activity of SR-PSOX. However, the cells expressing the construct of
      combination of R78A mutation in R76AK79A or R82AH85A could abolish these effects.
      More interestingly, the adhesive activities were remarkably down regulated in the
      cells expressing the multi-point mutants respectively. This study revealed that
      some conformational motifs of basic amino acid residues, especially R76 with K79
      in SR-PSOX, may form a common functional motif for its critical functions. R78 in
      SR-PSOX has the potential action to stabilize the function of oxLDL uptake and
      bacterial phagocytosis. The results obtained may provide new insight for the
      development of drug target of atherosclerosis.

PMID- 23009932
TI  - Role of additional novel therapies in myeloproliferative neoplasms.
AB  - The recent approval of ruxolitinib (INCB018424) for myelofibrosis and the
      preclinical/clinical development of several additional janus kinase (JAK)
      targeted agents have ushered in an era of novel therapies for advanced
      myeloproliferative neoplasms (MPN), which are associated with constitutive
      activation of the JAK-signal transducer and activation of transcription (STAT)
      signaling pathway. Collectively, these novel therapeutic approaches could rapidly
      broaden the spectrum of available therapies, with potential for improved clinical
      outcome for patients with advanced MPN. This review covers the recent
      developments in the testing of novel therapeutic agents other than JAK inhibitors
      that target signaling pathways in addition to JAK/STAT, or target the deregulated
      epigenetic mechanisms in MPN.

PMID- 23009933
TI  - Acquired uniparental disomy in myeloproliferative neoplasms.
AB  - The finding of somatically acquired uniparental disomy, where both copies of a
      chromosome pair or parts of chromosomes have originated from one parent, has led
      to the discovery of several novel mutated genes in myeloproliferative neoplasms
      and related disorders. This article examines how the development of single
      nucleotide polymorphism array technology has facilitated the identification of
      regions of acquired uniparental disomy and has led to a much greater
      understanding of the molecular pathology of these heterogeneous diseases.

PMID- 23009931
TI  - Differential regulation of GLUT1 activity in human corneal limbal epithelial
      cells and fibroblasts.
AB  - The corneal epithelial tissue is a layer of rapidly growing cells that are highly
      glycolytic and express GLUT1 as the major glucose transporter. It has been shown
      that GLUT1 in L929 fibroblast cells and other cell lines can be acutely activated
      by a variety agents. However, the acute regulation of glucose uptake in corneal
      cells has not been systematically investigated. Therefore, we examined glucose
      uptake in an immortalized human corneal-limbal epithelial (HCLE) cell line and
      compared it to glucose uptake in L929 fibroblast cells, a cell line where glucose
      uptake has been well characterized. We report that the expression of GLUT1 in
      HCLE cells is 6.6-fold higher than in L929 fibroblast cells, but the HCLE cells
      have a 25-fold higher basal rate of glucose uptake. Treatment with agents that
      interfere with mitochondrial metabolism, such as sodium azide and berberine,
      activate glucose uptake in L929 cells over 3-fold, but have no effect on glucose
      uptake HCLE cells. Also, agents known to react with thiols, such cinnamaldehyde,
      phenylarsine oxide and nitroxyl stimulate glucose uptake in L929 cells 3-4-fold,
      but actually inhibit glucose uptake in HCLE cells. These data suggest that in the
      fast growing HCLE cells, GLUT1 is expressed at a higher concentration and is
      already highly activated at basal conditions. These data support a model for the
      acute activation of GLUT1 that suggests that the activity of GLUT1 is enhanced by
      the formation of an internal disulfide bond within GLUT1 itself.

PMID- 23009934
TI  - Genotype-phenotype interactions in the myeloproliferative neoplasms.
AB  - The chronic myeloproliferative neoplasms (MPNs) are clonal disorders
      characterized by overproduction of mature myeloid cells. They share associations
      with molecular abnormalities such as the JAK2V617F mutation but are distinguished
      by important phenotypic differences. This review first considers the factors that
      may influence phenotype in JAK2-mutated MPNs, especially polycythemia vera (PV)
      and essential thrombocythemia (ET), and then discusses the mutations implicated
      in JAK2-negative MPNs such as in MPL and epigenetic regulators. Current evidence
      supports a model where ET and PV are disorders of relatively low genetic
      complexity, whereas evolution to myelofibrosis or blast-phase disease reflects
      accumulation of a higher mutation burden.

PMID- 23009935
TI  - Disordered signaling in myeloproliferative neoplasms.
AB  - The human myeloproliferative neoplasms (MPN) have long been associated with
      abnormal responses to cytokines and activation of signaling pathways, although
      the exact molecular mechanisms underlying these observations were unknown. This
      situation altered with the discovery of the JAK2 V617F, which presaged the
      ongoing description of further mutations predicted to activate canonical
      signaling pathways in MPN. This article covers the nature of these mutations and
      summarizes functional experiments in model systems and in human MPN cells to
      define the signaling pathways altered and how these drive and determine the MPN
      cellular phenotype. Also discussed are recently described, novel noncanonical
      signaling pathways to chromatin predicted to alter gene transcription more
      directly and to also contribute to the MPN phenotype.

PMID- 23009936
TI  - Role of germline genetic factors in MPN pathogenesis.
AB  - It is thought that myeloproliferative neoplasms (MPNs) are driven by somatic
      mutations, although hereditary factors also play a prominent role in the
      pathogenesis of the disease. Hereditary thrombocytosis and erythrocytosis are not
      malignant disorders but are clinically similar to MPNs. Several mutations have
      been found that explain a proportion of hereditary thrombocytosis and hereditary
      erythrocytosis. Germline variants can influence the risk of leukemic
      transformation in MPNs and the course of the disease through interaction with
      acquired chromosomal aberrations. Overall, it has been shown that germline
      factors play an important part in MPN pathogenesis.

PMID- 23009937
TI  - Role of TET2 and ASXL1 mutations in the pathogenesis of myeloproliferative
      neoplasms.
AB  - Since the discovery of activating mutations in JAK2 in patients with
      myeloproliferative neoplasms (MPNs) in 2005, gene discovery efforts have
      identified additional disease alleles, which can predate or occur subsequent to
      acquisition of JAK2/MPL mutations. In 2009, somatic copy number loss and
      mutations in the genes TET2 and ASXL1 were identified in MPN patients. Genetic
      analysis of MPN patient cohorts with adequate sample size and clear clinical
      annotation are needed to understand the importance of these mutations on MPN
      phenotype, risk of transformation to leukemia, response to therapy, and influence
      on overall survival.

PMID- 23009938
TI  - Myeloproliferative neoplasm animal models.
AB  - Myeloproliferative neoplasm (MPN) animal models accurately re-capitulate human
      disease in mice and have been an important tool for the study of MPN biology and
      therapy. Transplantation of BCR-ABL transduced bone marrow into irradiated
      syngeneic mice established the field of MPN animal modeling. Genetically
      engineered MPN animal models have enabled detailed characterization of the
      effects of specific MPN-associated genetic abnormalities on hematopoietic stem
      and progenitor cells (HSPCs). Xenograft models have allowed the study of primary
      human MPN-propagating cells in vivo. JAK2V617F, the most common molecular
      abnormality in BCR-ABL negative MPN, has been extensively studied using
      retroviral, transgenic, knock-in and xenograft models.

PMID- 23009941
TI  - Systemic mastocytosis: disease overview, pathogenesis, and treatment.
AB  - The clinical presentation of mastocytosis is diverse, and patients may not fit
      the classical description. Diagnosis requires a bone marrow examination,
      including immunohistochemical stains for mast cell tryptase or CD117. The
      treatment of adult systemic mastocytosis is highly individualized. This article
      presents an overview of systemic mastocytosis and describes its pathogenesis and
      treatment.

PMID- 23009940
TI  - Clinical predictors of outcome in MPN.
AB  - Myeloproliferative neoplasms include 3 diseases: polycythemia vera (PV),
      essential thrombocythemia (ET), and primary myelofibrosis (PMF). PV and ET are
      dominated by a high risk of thrombosis and a late risk of clonal evolution into
      secondary MF and acute myeloid leukemia. Patients with PMF may encounter many
      complications associated with disease progression or with PMF evolution. This
      article defines factors that determine prognosis in these 3 diseases.

PMID- 23009942
TI  - Non-CML myeloproliferative diseases. Preface.

PMID- 23009939
TI  - Therapy with JAK2 inhibitors for myeloproliferative neoplasms.
AB  - The development of JAK2 inhibitors followed the discovery of activating mutation
      of JAK2 (JAK2V617F) in patients with classic Philadelphia-negative
      myeloproliferative neoplasms (Ph-negative MPN). It is now known that mutations
      activating the JAK-STAT pathway are ubiquitous in Ph-negative MPN, and that the
      deregulated JAK-STAT pathway plays a central role in the pathogenesis of these
      disorders. JAK2 inhibitors thus are effective in patients both with and without
      the JAK2V617F mutation. This article reviews the rationale for using JAK2
      inhibitors in Ph-negative MPN, and the results of more recent clinical trials
      with these drugs.

PMID- 23009943
TI  - Imported scrub typhus in The Netherlands.
AB  - Two cases of travel-acquired scrub typhus imported in the Netherlands are
      described. The characteristic eschar was absent in both cases. One case acquired
      scrub typhus in non-rural surroundings in India, highlighting that scrub typhus
      must also be considered a (sub) urban zoonosis.

PMID- 23009944
TI  - Sexual asphyxia causing blunt carotid artery injury and Horner's syndrome.
AB  - OBJECTIVE: To highlight a rare cause of Horner's syndrome, and to review the
      management of blunt carotid artery injury. METHOD: Literature search via PubMed
      for related articles. RESULTS: Horner's syndrome and blunt carotid artery injury
      are rare phenomena; sexual asphyxia as a cause has not previously been reported.
      This case is also the first of its kind to have radiological evidence of injury
      to the external carotid artery but not the internal carotid artery. In Horner's
      syndrome, additional symptoms of ipsilateral headache or neck pain, tinnitus, or
      any cerebral ischaemic symptoms should raise suspicion of blunt carotid injury.
      CONCLUSION: Blunt carotid artery injury is a potentially fatal condition and can
      present without radiological evidence. Early recognition and management with
      anticoagulants or antiplatelet drugs is crucial to prevent mortality and
      morbidity.

PMID- 23009945
TI  - Assessing preference for social interactions.
AB  - We examined a procedure to assess preference for social interactions in
      individuals with intellectual and developmental disabilities. Preferences were
      identified in five individuals using a paired-choice procedure in which
      participants approached therapists who provided different forms of social
      interactions. A subsequent tracking test showed that participants' approaches
      were under control of the form of social interaction provided as opposed to
      idiosyncratic features of the therapists. Results of a reinforcer assessment
      found that the social interaction identified as preferred also functioned as a
      reinforcer for all five participants.

PMID- 23009946
TI  - Two women with multiple disabilities communicate with distant partners via a
      special text messaging system.
AB  - This study extended the research on a special text messaging system, which allows
      persons with multiple disabilities to (a) write and send messages to distant
      partners and (b) have messages from those partners read out to them. The study
      involved two women with multiple disabilities (including blindness or minimal
      residual vision). The system comprised a net-book computer, a mobile
      communication modem, and an input microswitch, and relied on special keyboards
      (not used before) to allow the women to write their messages. One of the
      keyboards included (a) two rows of 10 and 11 keys, respectively, reporting the 21
      basic letters of the Italian alphabet arranged in alphabetical order and marked
      with Braille labels and (b) a space bar and an enlarged back/erase key. The other
      keyboard had Braille cues on the initial, central, and final keys of the letter
      rows. Moreover, most function keys were covered (cut out from the usable space).
      Both women learned to use the messaging system with the special keyboards
      successfully (i.e., to write their messages, to send them out, and to listen to
      incoming messages). These findings are analyzed in relation to preliminary data
      with the system and the need to adapt the writing technology to the participants'
      characteristics.

PMID- 23009947
TI  - [Neuroendocrine pancreatic tumors and helpfulness of targeted therapies].
AB  - The neuroendocrine pancreatic tumors are rare tumors, but their incidence is
      constantly rising. Even if the management of these tumors has to be surgical as
      soon as possible, the disease is most often metastatic at the stage of the
      diagnostic. The prognostic and the therapeutic options differ from pancreatic
      adenocarcinoma. Available treatments have evolved over the last years with recent
      publications of studies that bring to light the benefits of targeted therapies in
      this pathology. This has resulted in modifications of both practices and either
      French and international guidelines. Therefore, we focus on the management of the
      grade 1 and grade 2 well-differentiated neuroendocrine pancreatic tumors as
      classified in new WHO classification of neuroendocrine neoplasms published in
      2010.

PMID- 23009948
TI  - Developmental stage of strongyle eggs affects the outcome variations of real-time
      PCR analysis.
AB  - Strongyle and trichostrongyle parasites are ubiquitous nematodes of grazing
      livestock. Several molecular diagnostic tests are based upon measuring and
      quantifying DNA obtained from parasite eggs. It is well known that such eggs
      undergo development during storage, but it remains unknown to which extent
      developmental stages can affect the variation of diagnostic test results. This
      study investigated the influence of developmental stages of strongyle eggs on the
      variation real-time polymerase chain reaction (PCR) results. Mixed species
      strongyle eggs were obtained from the faeces of a naturally infected horse. Eggs
      were isolated and placed in microtiter plates with demineralized water. A total
      of 25 wells containing 100 eggs each were set up and kept refrigerated for up to
      five days. Once daily, five wells were examined on an inverted microscope at 100*
      magnification, where the developmental stages of the eggs were noted, and then
      eggs harvested for DNA extraction. The protocol was repeated three times. Genomic
      DNA was extracted using a commercial kit previously validated for strongyle type
      eggs. PCR reactions were performed with a primer set specific for the ribosomal
      DNA region for all strongyle type parasites (NC1, NC2). SYBR Green Real-Time PCRs
      were performed in triplicates. Results revealed a statistically significant
      increase in PCR yield after three days, which was statistically associated with
      beginning embryonation of the eggs. In conclusion, storage time and developmental
      stage of strongyle eggs are significant sources of error in studies based on
      quantitative real-time PCR analysis. This study suggests that for refrigerated
      storage of more than three days, eggs should be inactivated and preserved for
      further analysis.

PMID- 23009949
TI  - Multi-organ hydatidosis with extensive involvement of the hemi-pelvis and
      ipsilateral femur.
AB  - Bone involvement of hydatid disease is uncommon but when encountered, it presents
      few unique pathological features. The pattern of tissue involvement is largely
      different from that of visceral hydatid cyst. We describe the case of a 47 year
      old man from northern India, a case of systemic hydatidosis including the liver
      and the right lung, presenting with an abscess like lesion in the left gluteal
      region with pathological fractures of the left femur. Radiographs and CT-scan
      images showed extensive invasion of the left hemi-pelvis and left proximal femur.
      Debridement of the honeycombed ilium yielded hydatid fluid, numerous small cysts
      and necrotic material. Multiple large devitalized and sequestrated bone pieces
      were recovered from the bone cavity of the affected ilium. A histopathological
      study of the bone sequestrums revealed the unique pattern of bone invasion by the
      characteristic laminated multi-layered cyst walls into areas of least resistance.
      Bone sequestration has not often been described or demonstrated elaborately in
      published studies of the past. The bone defects formed after debridement of the
      ilium and proximal femur were filled with bone cement along with augmentation of
      the femur using intra-medullary nail. The surgical technique adopted in our case
      although was not expected to be curative owing to the multi-system disease; it
      did result in significant functional improvement in the patient.

PMID- 23009950
TI  - Quantitative proteomic analysis reveals protein expression changes in the murine
      neuronal secretome during apoptosis.
AB  - Neurodegenerative diseases often lack early and specific diagnostic and
      prognostic biomarkers. Many studies are focusing on the cerebrospinal fluid (CSF)
      proteome to identify relevant biomarkers and therapeutic targets for these
      disorders. An alternative approach consists in comparing proteins secreted by
      healthy neurons and neurons degenerating by apoptosis, one of the mechanisms
      underlying neuronal death in neurodegenerative diseases. Here, we adapted the
      stable isotope labeling by amino acids in cell culture (SILAC) technology to
      primary cultures of mouse cerebellar granule neurons (CGNs), a well-characterized
      in vitro model of neuronal apoptosis, in order to identify variations in protein
      release by neurons during apoptosis. Using two different heavy isotope labels
      followed by liquid chromatography coupled with Fourier transform tandem mass
      spectrometry, we directly compared the secretome of apoptotic and surviving CGNs.
      A total of 1375 proteins were identified in CGN-conditioned media. Among these
      proteins, 47 were differentially expressed in the supernatants of apoptotic and
      surviving neurons. About 50% of them have been previously identified in human CSF
      and some are involved in neuronal death or neuroprotection. This list of
      apoptosis-regulated proteins should be considered when using targeted
      quantitative proteomics approaches to characterize or validate CSF biomarkers of
      neurodegenerative disorders.

PMID- 23009952
TI  - [Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome].

PMID- 23009951
TI  - Global effects of subchronic treatment of microcystin-LR on rat splenetic protein
      levels.
AB  - Microcystin-LR (MCLR), released by toxic cyanobacterial blooms, has received
      worldwide concerns in the past decades for its hepatotoxicity. Recent studies
      show that microcystins (MCs) can be accumulated in immune organs and exert
      notable immunotoxicity. In order to better understand cellular responses in
      immune tissues disrupted by MCLR treatment, this work mainly focuses on the
      spleen impairments of rats. After a subchronic 50 d exposure (1 or 10 MUg/kg body
      weight per day), spleen index, MCLR accumulation, histological change and plasma
      lysozyme activity were detected in MCLR-treated rat. Results indicated that
      prolonged exposure of MCLR led to toxin accumulation and caused severe damage in
      spleen of rats, and eventually impaired the immune functions. To further our
      understanding of the toxic effects of MCLR on the spleen and the mechanisms
      behind it, a proteomic analysis was performed to determine the global effects of
      MCLR on splenetic protein levels. In total, 48 proteins were identified and
      showed a significant increase or decrease in abundance compared to the control
      after MCLR exposure. These proteins are mainly involved in immune response,
      oxidative stress, energetic metabolism and the cytoskeleton assembly, indicating
      that MCLR exerts complex toxic effects in rat spleen and jointly results in
      immunotoxicity.

PMID- 23009953
TI  - Potassium restores vasorelaxation of resistance arterioles in non-hypertensive
      DOCA/salt fed mice.
AB  - BACKGROUND: Potassium-enriched diets exert renal and cardiovascular protective
      effects, but the underlying mechanisms are largely unknown. METHODS: Using the
      dorsal skinfold chamber model for intravital microscopy, we examined endothelium
      dependent vasorelaxation of precapillary resistance arterioles in response to
      acetylcholine or the NO donor SNAP in awake mice. Experiments were performed in
      uni-nephrectomized one renin gene (Ren-1c) C57BL/6 mice (control group) and in
      mice having received a continuous administration of deoxycorticosterone acetate
      and a dietary supplementation of 1% sodium chloride for 8 weeks (DOCA/salt
      group). An additional group of DOCA/salt treated animals received a dietary
      supplement of 0.4% KCl for 3 weeks prior to the experiments (DOCA/salt +
      potassium group). RESULTS: DOCA/salt treatment for 8 weeks resulted in
      hypokalemia, but blood pressure remained unchanged. In DOCA/salt mice, relaxation
      of resistance arterioles was blunted in response to acetylcholine, and to a
      lesser extent to SNAP, suggesting endothelial dysfunction. Endothelium-dependent
      vasorelaxation was restored by the potassium-enriched diet. CONCLUSION: This
      study is the first to demonstrate a protective effect of potassium on endothelium
      dependent vasorelaxation in the absence of confounding anti-hypertensive effects,
      as observed in most animal models and the clinical situation. We propose that the
      known cardio- and nephro-protective effects of potassium might - at least in part
      - be mediated by the salutary effects on endothelium-dependent arteriolar
      relaxation.

PMID- 23009954
TI  - High prevalence of retinal endothelial dysfunction in obesity WHO class III.
AB  - BACKGROUND: The extent of retinal endothelial dysfunction (ED) in patients with
      obesity is unknown. We evaluated markers of endothelial dysfunction to assess
      cardiovascular risk in patients with obesity WHO III degrees  and their
      interrelation with classical cardiovascular risk factors. METHODS: 120 patients
      (mean age 42.7+/-10.6 years, 87 women) were prospectively evaluated for metabolic
      and cardiovascular risk using anthropometry, cardiovascular risk factors, lipid
      and glucose profiles. Intima media thickness (IMT) as marker of subclinical
      atherosclerosis, ED of retinal vessels, and the arteriole-to-venule ratio (AVR)
      of retinal vessels were assessed. RESULTS: The mean BMI in our cohort was 48.7
      kg/m(2). We diagnosed an overall prevalence of impaired glucose metabolism of
      69.2%. 71.6% and 65.2% presented with arterial hypertension or dyslipidemia,
      respectively. Prevalences of retinal ED, pathologically reduced AVR, and enlarged
      IMT were 62.7%, 56.6% and 30%, respectively. Markers of endothelial function
      demonstrated correlation of neck to height ratio with dilatation of arteries (r=
      0.333, p=0.01) and HDL cholesterol with dilatation of veins (r=-0.393, p=0.002).
      AVR was significantly related to neck circumference (r=-0.269, p=0.004).
      CONCLUSION: Retinal ED, AVR, and IMT as direct noninvasive surrogate measures of
      cardiovascular risk showed a high prevalence in patients with obesity WHO III
      degrees . We found no association of classical parameters for metabolic or
      cardiovascular risk with markers of endothelial dysfunction. Therefore, we have
      to hypothesize that other factors also play a pivotal role in the development of
      vascular pathology in patients with obesity.

PMID- 23009955
TI  - Analysis of cognitive, functional, health service use, and cost trajectories
      prior to and following memory loss.
AB  - OBJECTIVES: This brief report examines whether significant changes in cognition,
      functional dependence, health service use, and out-of-pocket medical expenditures
      (OOPMD) occur in the years prior to a physician-identified memory problem in a
      nationally representative sample of older adults. METHOD: Longitudinal data from
      the RAND-Health and Retirement Survey were utilized. Those who reported a
      physician-identified memory problem (n = 387) were compared with a randomly
      selected control group of similar age, race, and gender who did not indicate a
      memory problem (n = 387). Multilevel linear models were used to construct
      trajectories for various measures of cognition, function, health service use, and
      OOPMD in the years prior to and following memory problem identification. RESULTS:
      Several trajectories demonstrated significant rates of change in the years
      leading up to a physician-identified memory problem, including symptoms (mental
      status, fine motor skills, and instrumental activities of daily living) and
      utilization (OOPMD and overnight stays in hospital). DISCUSSION: Preclinical
      declines in mental status and function and increases in hospital use and OOPMD
      are apparent prior to the formal identification of memory problems. Earlier
      identification of these changes might provide a basis for interventions that
      could alter the clinical course of dementia.

PMID- 23009956
TI  - Aging and visual crowding.
AB  - OBJECTIVES: The ability to perceive high spatial frequencies (i.e., fine detail)
      is impaired when contours are placed near the detail to be resolved (Bouma, H.
      [1970]. Interaction effects in parafoveal letter recognition. Nature, 226, 177
      178. doi:10.1038/226177a0; Flom, M. C., Weymouth, F. W., & Kahneman, D. [1963].
      Visual resolution and contour interaction. Journal of the Optical Society of
      America A, 53, 1026-1032. doi:10.1364/JOSA.53.001026.). This visual crowding is
      more pronounced outside of central vision and may be more pronounced in older
      adults. Thus, the motivation for the present study. METHOD: Younger (M = 20.95
      years) and older adults (M = 70.32 years) detected gap orientation in a Landolt C
      presented at 3 degrees  or 6 degrees  either alone or flanked by bars of the same
      spatial scale. RESULTS: Both age groups demonstrated a visual crowding effect, in
      that acuity deteriorated in the flanking condition, an effect that grew with
      eccentricity. Older adults exhibited a larger crowding effect, particularly at 6
      degrees . Younger adults tested at reduced illumination did not show the crowding
      effect of older adults. Thus, age differences do not appear to result from
      reduced retinal illumination. When the crowding effect was operationalized as the
      ratio of crowded to uncrowded acuity, age differences were eliminated at both 3
      degrees  and 6 degrees . DISCUSSION: These data have implications for
      understanding age differences in functional vision, including reading and visual
      search.

PMID- 23009957
TI  - Social support, stressors, and frailty among older Mexican American adults.
AB  - BACKGROUND: There is little research on the effects of stressors and social
      support on frailty. Older Mexican Americans, in particular, are at higher risk of
      medical conditions, such as diabetes, that could contribute to frailty. Given
      that the Mexican American population is rapidly growing in the United States, it
      is important to determine whether there are modifiable social factors related to
      frailty in this older group. METHOD: To address the influence of social support
      and stressors on frailty among older Mexican Americans, we utilized five waves of
      the Hispanic Established Populations for the Epidemiologic Study of the Elderly
      (Hispanic EPESE) to examine the impact of stressors and social support on frailty
      over a 12-year period. Using a modified version of the Fried and Walston Frailty
      Index, we estimated the effects of social support and stressors on frailty over
      time using trajectory modeling (SAS 9.2, PROC TRAJ). RESULTS: We first grouped
      respondents according to one of three trajectories: low, progressive moderate,
      and progressive high frailty. Second, we found that the effects of stressors and
      social support on frailty varied by trajectory and by type of stressor. Health
      related stressors and financial strain were related to increases in frailty over
      time, whereas social support was related to less-steep increases in frailty.
      CONCLUSION: Frailty has been hypothesized to reflect age-related physiological
      vulnerability to stressors, and the analyses presented indicate partial support
      for this hypothesis in an older sample of Mexican Americans. Future research
      needs to incorporate measures of stressors and social support in examining those
      who become frail, especially in minority populations.

PMID- 23009958
TI  - What mom and dad don't know can hurt you: adolescent disclosure to and secrecy
      from parents about type 1 diabetes.
AB  - OBJECTIVE: To examine how adolescent disclosure to and secrecy from parents were
      related to parental knowledge of diabetes management behaviors, and to adolescent
      adherence, metabolic control, and depressive symptoms. METHODS: A total of 183
      adolescents with type 1 diabetes reported on disclosure to and secrecy from
      parents regarding diabetes management, adherence behaviors, depressive symptoms,
      and perceptions of parental knowledge. Mothers and fathers reported on their own
      knowledge. RESULTS: Adolescent disclosure was associated with all reporters'
      perceptions of knowledge. Secrecy from both parents moderated the relationship
      between disclosure and adherence, and secrecy from fathers moderated the
      relationship between disclosure to fathers and glycosylated hemoglobin level. In
      all cases, disclosure was associated with better diabetes management only when
      secrecy was low. Finally, higher secrecy related to greater adolescent depressive
      symptoms. CONCLUSIONS: Disclosure to parents appears to be an important component
      of how parents get their knowledge about adolescents' diabetes management, but
      may be most beneficial for diabetes management when it occurs together with low
      secrecy.

PMID- 23009959
TI  - Test-retest reliability of the BOLD pharmacological MRI response to ketamine in
      healthy volunteers.
AB  - The pharmacological MRI (phMRI) technique is being increasingly used in both pre
      clinical and clinical models to investigate pharmacological effects on task-free
      brain function. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist,
      induces a strong phMRI response and represents a promising pharmacological model
      to investigate the role of glutamatergic abnormalities in psychiatric
      symptomatology. The aim of this study was to assess whether the brain response to
      ketamine is reliable in order to validate ketamine phMRI as a mechanistic marker
      of glutamatergic dysfunction and to determine its utility in repeated measures
      designs to detect the modulatory effect of other drugs. Thus we assessed the test
      retest reliability of the brain response to ketamine in healthy volunteers and
      identified an optimal modelling approach with reliability as our selection
      criterion. PhMRI data were collected from 10 healthy male participants, at rest,
      on two separate occasions. Subanaesthetic doses of I.V. ketamine infusion (target
      plasma levels 50 ng/mL and 75 ng/mL) were administered in both sessions. Test
      retest reliability of the ketamine phMRI response was assessed voxel-wise and on
      pre-defined ROIs for a range of temporal design matrices including different
      combinations of nuisance regressors designed to model shape variance, linear
      drift and head motion. Effect sizes are also reported. All models showed a
      significant and widespread response to low-dose ketamine in predicted cerebral
      networks and as expected, increasing the number of model parameters improved
      model fit. Reliability of the predefined ROIs differed between the different
      models assessed. Using reliability as the selection criterion, a model capturing
      subject motion and linear drift performed the best across two sessions. The
      anatomical distribution of effects for all models was consistent with results of
      previous imaging studies in humans with BOLD signal increases in regions
      including midline cingulate and supracingulate cortex, thalamus, insula, anterior
      temporal lobe and ventrolateral prefrontal structures, and BOLD signal decreases
      in the subgenual cingulate cortex. This study represents the first investigation
      of the test-retest reliability of the BOLD phMRI response to acute ketamine
      challenge. All models tested were effective at describing the ketamine response
      although the design matrix associated with the highest reliability may represent
      a robust and well-characterised ketamine phMRI assay more suitable for repeated
      measures designs. This ketamine assay is applicable as a model of
      neurotransmitter dysfunction suitable as a pharmacodynamic imaging tool to test
      and validate modulatory interventions, as a model of NMDA hypofunction in
      psychiatric disorders, and may be adapted to understand potential antidepressant
      and analgesic effects of NMDAR antagonists.

PMID- 23009960
TI  - Introduction. Cesarean delivery.

PMID- 23009961
TI  - Epidemiology of cesarean delivery: the scope of the problem.
AB  - Approximately one-third of births in the United States are via cesarean delivery
      (CD). The rate of CD has increased dramatically since the 1990s, reaching a peak
      of 32.9% in 2009. The increase can be seen among women of all ages and
      race/ethnicities, in every state, and across all gestational ages. The primary CD
      rate has increased from 14.5% in 1996 to 23.4% in 2007. Because the primary CD
      rate has increased and the rate of trial of labor after CD has decreased, the
      primary cesarean rate has become a major driver in the total CD rate. Also
      contributing to the high CD rate is an increase in somewhat subjective
      indications, such as fetal distress or nonreassuring fetal tracing and failure to
      progress leading to performance of CD in the latent phase of labor. Addressing
      these factors--as well as focusing on the use of elective induction and
      management of early labor in the particular subgroup of nulliparous women at
      term, with singleton fetuses in vertex presentation--may have a significant
      impact on the total CD rate.

PMID- 23009962
TI  - Implications of the first cesarean: perinatal and future reproductive health and
      subsequent cesareans, placentation issues, uterine rupture risk, morbidity, and
      mortality.
AB  - Rates of cesarean delivery have substantially increased worldwide during the past
      30 years. Indeed, almost one-third of deliveries in the United States are
      cesareans. Most cesareans are safe, and major complications are uncommon.
      However, there is a "concealed" downside to cesarean deliveries. There are rare
      but life-threatening morbidities that may occur, which are often overlooked
      because most cesareans go well. In addition, subsequent pregnancies are fraught
      with an increased risk of both maternal and fetal complications. The worst of
      these are associated with placental problems such as previa, abruption, and
      accreta. The risk dramatically worsens in patients with multiple repeat cesarean
      deliveries. This article will summarize and highlight the implications of the
      rising cesarean rate on maternal and fetal morbidity and mortality.

PMID- 23009963
TI  - When is primary cesarean appropriate: maternal and obstetrical indications.
AB  - To describe appropriate maternal and obstetrical indications for primary cesarean
      delivery. The list of potential indications is long. Among all maternal and
      obstetrical indications, labor dystocia is the most common; multifetal pregnancy
      and malpresentation are not infrequent. Maternal indications, including human
      immunodeficiency virus (with high viral load) and herpes simplex virus (with
      active lesions), are rare. Preeclampsia alone typically is not an appropriate
      indication for cesarean delivery. Although the need for a cesarean is absolute
      for some conditions, such as complete placenta previa or placenta accreta,
      minimum criteria for a cesarean are variable and subjective for many indications,
      including dystocia. The subjective diagnosis of labor dystocia provides the best
      opportunity to prevent the first cesarean.

PMID- 23009964
TI  - When is primary cesarean appropriate: fetal indications.
AB  - The objective of this review was to assess the evidence that supports cesarean
      delivery for fetal indications. The main fetal reasons for abdominal delivery
      include abnormal fetal heart rate patterns in labor, malpresentation, fetal
      macrosomia, multiple gestation, and both functional and structural fetal
      abnormalities. Although the level of evidence is not as strong as anticipated,
      there is sufficient support for cesarean delivery when these fetal conditions
      complicate pregnancy. Efforts to decrease cesarean delivery for fetal indications
      in the current medicolegal environment will not be easy; however, the development
      of more sensitive tools to assess fetal well-being in labor and practices to
      deliver or reduce fetuses in breech presentation at term have the potential for
      greatest impact on the overall primary cesarean delivery rate.

PMID- 23009965
TI  - Induction of labor in the United States: a critical appraisal of appropriateness
      and reducibility.
AB  - Approximately 1 in 4 women in the United States are induced, with up to 1 in 10
      12 being induced for elective reasons. National guidelines by the American
      College of Obstetricians and Gynecologists, the Society of Obstetricians
      Gynaecologists of Canada, and the Royal College of Obstetricians and
      Gynaecologists list 21 indications for inductions; however, all 3 concur in only
      14% women (3 of 21). An induction should be considered appropriate if it meets
      the following 4 criteria: (1) concordant with women's autonomous informed
      decisions and desideratum; (2) optimizes maternal-fetal outcomes, including
      psychological maternal well-being; (3) congruous with evidence-based medicine;
      and (4) cost-effective. A meta-analysis of 22 randomized trials noted that
      membrane sweeping reduces the likelihood of induction. Implementing policies to
      prevent elective induction at 37-38 weeks provides conflicting results about the
      rate of macrosomia and stillbirth at early term. We argue that a well-designed
      randomized controlled trial, with adequate power to demonstrate whether
      prohibiting elective induction increases the rate of stillbirth or complications
      such as macrosomia, is warranted. Patient education during their prenatal course
      is a promising strategy to decrease the rate of induction.

PMID- 23009966
TI  - Predictors of induction success.
AB  - If the prediction of induction success is to be used as a tool to lower the
      frequency of a first cesarean delivery, such prediction would need to be among
      women who are undergoing elective induction, and would need to indicate which
      women are more likely to have cesarean if they are induced as opposed to
      expectantly managed. This review summarizes the data that link elective labor
      induction and cesarean delivery, as well as the factors (or lack thereof) that
      may be used to better understand which women who are induced ultimately have a
      vaginal delivery.

PMID- 23009967
TI  - Current methods of labor induction.
AB  - In 2009, approximately 23% of all pregnant women in the United States underwent
      induction of labor, which is more than double the incidence of 9.5% in 1990. The
      ultimate goal of labor induction is to achieve vaginal delivery by stimulating
      uterine contractions before the spontaneous onset of labor. Labor induction is
      clearly indicated when the benefits outweigh the maternal and fetal risks of
      continued gestation, as well as potential risks associated with the procedure.
      Many women undergoing labor induction require cervical ripening--a method to
      facilitate softening, thinning, and dilation of an unfavorable cervix--because it
      reduces the time to delivery and incidence of failed induction. This article
      summarizes currently available methods for labor induction and cervical ripening,
      advantages and disadvantages of various methods, and the safety and effectiveness
      of each method based on well-conducted clinical trials.

PMID- 23009968
TI  - The influence of analgesia on labor--is it related to primary cesarean rates?
AB  - Multiple observational studies have reported an association between neuraxial
      (epidural, spinal, or combined spinal-epidural) labor analgesia and cesarean
      delivery. The purpose of this review is to summarize data from controlled trials
      addressing the question of whether neuraxial labor analgesia causes an increased
      risk of cesarean delivery. Additionally, the review will discuss whether the
      timing of initiation of analgesia or the specific type of neuraxial analgesia
      influences mode of delivery. Finally, the issue of external validity of published
      trials will be discussed.

PMID- 23009970
TI  - Prevention of the first cesarean delivery: the role of operative vaginal
      delivery.
AB  - While the cesarean delivery (CD) rates have increased worldwide, operative
      vaginal delivery (OVD) rates continue to decline, with the United States having
      some of the lower rates amongst developed countries. It is clear that the use of
      forceps or vacuum can safely assist in accomplishing a vaginal delivery and
      prevent a cesarean during the IInd stage of labor performed for a variety of
      maternal or fetal indications. In the absence of randomized trials between OVD's
      and immediate CD's for anticipated difficult births the question of the balance
      of risks between the two interventions remains unanswered. Properly performed
      OVD's are associated with lower maternal morbidity compared with cesarean,
      without an increase in significant neonatal morbidity. In order to reverse the
      current trends and for these skills to continue active training in OVD's is
      clearly needed during and after residency. The availability of clinicians with
      expertise in OVD's should aid in decreasing the rates of CD and the training of
      newer generations of practitioners. The professional endorsement of OVD's is also
      fundamental not only to frame the practice for physicians but to promote and
      improve the general acceptance of assisted deliveries and facilitate the societal
      discourse to reduce CD rates.

PMID- 23009969
TI  - Preventing primary cesarean sections: intrapartum care.
AB  - Some intrapartum care practices promote vaginal birth, whereas others may
      increase the risk for cesarean section. Electronic fetal monitoring and use of
      the Friedman graph to plot and monitor labor progress are associated with
      increasing the cesarean section rate. Continuous one-to-one support and midwifery
      management are associated with lower cesarean section rates. This article reviews
      the evidence that links specific intrapartum care practices to cesarean section.
      Strategies that can be implemented in the current social and cultural setting of
      obstetrics today are recommended.

PMID- 23009972
TI  - The first cesarean: role of "fetal distress" diagnosis.
AB  - The goal of this review is to synthesize the available information regarding
      factors leading to the first cesarean, especially as it relates to the role of
      electronic fetal heart rate monitoring (EFM) in the prevention of the first
      cesarean. The widespread use of EFM did not reduce perinatal or neonatal adverse
      outcomes. Coupled with its inherent problems, such as poor sensitivity and
      reliability, this has led to a dramatic increase in cesarean delivery rates. To
      be realistic in any attempt to lower the current cesarean rate, we must address
      the inherent limitations in our current EFM methods.

PMID- 23009971
TI  - Diagnosis and management of arrest disorders: duration to wait.
AB  - To assess the thresholds of normal and protracted labor in contemporary US
      parturients. Select studies addressing first- and second-stage labor duration
      among contemporary cohorts of women in the United States were reviewed.
      Particular emphasis was placed on the work of the Consortium on Safe Labor.
      Duration of labor appears longer today than in the past. For both nulliparous and
      multiparous women, labor may take >6 hours to progress from 4 to 5 cm and >3
      hours to progress from 5 to 6 cm of dilation. A cervical dilation of 6 cm appears
      to be a better landmark for the start of the active phase. The 95th percentile
      for duration of the second stage in a nulliparous woman with conduction
      anesthesia is closer to 4 hours. Current data on first and second stages of labor
      allow for an opportunity to reconsider traditionally accepted thresholds of
      normal and protracted labor, and thus affect consequent labor management
      paradigms.

PMID- 23009973
TI  - Decision making for primary cesarean delivery: the role of patient and provider
      preferences.
AB  - Primary cesarean delivery requires both the clinical assessment and judgment of
      the provider performing the procedure and the consent of the patient. The
      interaction between patient and provider and the relative weight and influence of
      patient preferences and provider recommendations may vary depending on whether a
      cesarean delivery is planned or unplanned, elective or indicated; understanding
      the range of contexts in which decision making takes place and the interplay of
      patient and provider factors in each of these situations is crucial to
      identifying ways to impact the cesarean rate that are safe and acceptable to both
      patients and providers. We conducted a review of the literature on patient and
      provider preferences and obstetrical decision making in the context of primary
      cesarean delivery, and offer recommendations for future research directions,
      including potential interventions that may impact the patient and provider
      factors affecting the primary cesarean rate.

PMID- 23009974
TI  - Fear of litigation and cesarean section rates.
AB  - Both the rates of cesarean section and the rates and payouts from obstetrical
      malpractice suits have risen in past decades, albeit not always in tandem. A
      great deal of evidence suggests that physicians practice defensive medicine, and
      many obstetricians acknowledge that a more liberal recourse to cesarean section
      is one such behavior in which they sometimes engage. However the degree to which
      fear of litigation actually is a contributor to, or perhaps even a driver of, the
      rising cesarean section rate is not as clearly known. In this article I will
      discuss the research that has been performed that attempts to epidemiologically
      assess the link between lawsuits, malpractice premiums and cesarean section
      rates. I will also consider factors beyond dollars and cents (e.g., cognitive
      biases, changing risk tolerance of doctors and patients) that may lie at the base
      of the relationship. Finally I will offer a brief discussion of how professional
      ethics should inform the actions that physicians take in these difficult
      circumstances.

PMID- 23009975
TI  - Impact of non-clinical factors on primary cesarean deliveries.
AB  - The patient characteristics that influence cesarean rates are well known.
      However, there are many non clinical factors that also influence cesarean rates.
      Understanding these non clinical factors and how they can be changed to improve
      care is an important part of obstetrics. Provider staffing patterns, the types of
      providers and how information can be used to effectively change practice patterns
      are explored in this article.

PMID- 23009976
TI  - The influence of practice management on primary cesarean birth.
AB  - As the cesarean delivery rate has increased to once unimaginable levels,
      obstetricians should question the loss of our credibility. Older mothers,
      obesity, larger birth weights, too many twins, and no more breech vaginal
      deliveries have all been cited as contributing factors to the increase in primary
      cesarean birth, but one cannot neglect the influence of physician practice style.
      Attempts to curtail or reverse the escalating incidence of primary abdominal
      deliveries should focus on caution with inductions of labor, patience with the
      management of arrest disorders, more accurate assessment of fetal compromise,
      patient education and informed decision making about the benefits/risks of
      operative delivery, and improvement in the medicolegal environment.

PMID- 23009977
TI  - Informing the patient and the community about the implications of primary
      cesarean.
AB  - Education of patients and the community should begin with an acknowledgment of
      the increase in primary and secondary morbidity and mortality associated with the
      initial cesarean delivery. Women with cesarean birth have a higher rate of
      rehospitalization for various indications, including surgical site infections.
      The direct cost for cesarean-related surgical site infection alone is in the tens
      of millions of dollars. It is important for patients to appreciate risk factors
      that lead to an increase the risk for primary cesarean, such as obesity, and
      medical comorbidities. Education on these factors allows in some instances for
      preconception interventions that can potentially lower the risk for primary
      cesarean. The obstetrician and the maternal fetal medicine subspecialist have an
      obligation to focus on evidence-based obstetrical practices that can lead to a
      more acceptable primary cesarean rate for the obstetrical population. Patient and
      community awareness can contribute to the promotion of this expectation in
      obstetrical practice.

PMID- 23009978
TI  - Comparative histomorphological assessment of the testes of two Clarias species
      from the Okavango Delta Panhandle, Botswana.
AB  - The testes of two Clarias species from the Okavango Delta Panhandle were
      histomorphologically assessed for differences in structure mainly because the
      testes varied externally in colour, with Clarias ngamensis having black testes
      while those of Clarias gariepinus were off-white. Although a detailed
      histological description of normal testes in C. gariepinus has been compiled
      based on laboratory experimentation, there is limited histomorphological field
      data available on both species which could be used as reference material in the
      histology and histomorphology assessment of gonads both in the laboratory and
      field experiments. In August 2006 and 2007 fifteen fish per species of C.
      ngamensis and C. gariepinus were collected from the Shakawe Panhandle in the
      Okavango Delta. Testicular samples excised from the fish were fixed in 10%
      neutral buffered formalin and later transported to the University of Johannesburg
      where laboratory analyses using standard histological procedures were conducted.
      Microscopic assessments were used to describe the testicular morphology and the
      reproductive developmental stages. Haematoxylin and Eosin (H&E), Periodic Acid
      Schiff (PAS), Perl's Prussian Blue and Gordon and Sweets Silver Stain Solution
      were used to enhance finer cellular detail and the morphology of various
      structures present in the catfish testes. Results emanating from this study (a)
      form a histomorphological baseline set of data from an undisturbed wetland system
      for comparison between normal morphology and anomalies within the catfish
      species, (b) contribute to the limited database of the normal histomorphology of
      gonads in Southern African freshwater fish species and (c) expand the academic
      knowledge and skills required for the conservation of wetland ecosystems in
      Southern Africa.

PMID- 23009979
TI  - An unusual case of aggressive systemic mastocytosis with associated refractory
      plasma cell myeloma.

PMID- 23009980
TI  - A case of type B lactic acidosis in multiple myeloma.

PMID- 23009981
TI  - Factors associated with delayed activation of medical emergency team and excess
      mortality: an Utstein-style analysis.
AB  - AIM: We used the Utstein template, with special reference to patients having
      automated patient monitoring, and studied the factors which are associated with
      delayed medical emergency team (MET) activation and increased hospital mortality.
      DESIGN AND SETTING: A prospective observational study in a tertiary hospital with
      45 of 769 general ward beds (5.9%) equipped with automated monitoring. COHORT:
      569 MET reviews for 458 patients. RESULTS: Basic MET review characteristics were
      comparable to literature. We found that 41% of the reviews concerned monitored
      ward patients. These patients' vitals had been more frequently documented during
      the 6h period preceding MET activation compared to patients in normal ward areas
      (96% vs. 74%, p<0.001), but even when adjusted to the documentation frequency of
      vitals, afferent limb failure (ALF) occurred more often among monitored ward
      patients (81% vs. 53%, p<0.001). In MET population, factors associated with
      increased hospital mortality were non-elective hospital admission (OR 6.25, 95%
      CI 2.77-14.11), not-for-resuscitation order (3.34, 1.78-6.35), ICD XIV
      genitourinary diseases (2.42, 1.16-5.06), ICD II neoplasms (2.80, 1.59-4.91), age
      (1.02, 1.00-1.04), preceding length of hospital stay (1.04, 1.01-1.07), ALF
      (1.67, 1.02-2.72) and transfer to intensive care (1.85, 1.05-3.27). CONCLUSIONS:
      Documentation of vital signs before MET activation is suboptimal. Documentation
      frequency seems to increase if automated monitors are implemented, but our
      results suggest that benefits of intense monitoring are lost without appropriate
      and timely interventions, as afferent limb failure, delay to call MET when
      predefined criteria are fulfilled, was independently associated to increased
      hospital mortality.

PMID- 23009982
TI  - Suggested change to Resuscitation Council guidelines on reversible causes of
      cardiac arrest: acute subarachnoid haemorrhage, and malignant tachyarrhythmia.

PMID- 23009983
TI  - Evaluation of anti-cancer activity of Acanthester planci extracts obtained by
      different methods of extraction.
AB  - Acanthaster planci, the crown-of-thorns starfish, naturally endowed with the
      numerous toxic spines around the dorsal area of its body. Scientific
      investigations demonstrated several toxico-pharmacological efficacies of A.
      planci such as, myonecrotic activity, hemorrhagic activity, hemolytic activity,
      mouse lethality, phospholipase A2 (PLA2) activity, capillary permeability
      increasing activity, edema-forming activity, anticoagulant activity and histamine
      releasing activity from mast cells. The present study was performed to evaluate
      the cytotoxic activity of A. planci extracts obtained by different methods of
      extraction on MCF-7 and HCT-116, human breast and colon cancer cell lines,
      respectively. Results of the cell proliferation assay showed that PBS extract
      exhibited very potent cytotoxic activity against both MCF-7 and HCT-116 cell
      lines with IC(50) of 13.48 MUg/mL and 28.78 MUg/mL, respectively, while the
      extracts prepared by Bligh and Dyer method showed moderate cytotoxicity effect
      against MCF-7 and HCT-116 cell lines, for chloroform extract, IC(50) = 121.37
      MUg/mL (MCF-7) and 77.65 MUg/mL (HCT-116), and for methanol extract, IC(50) =
      46.11 MUg/mL (MCF-7) and 59.29 MUg/mL (HCT-116). However, the extracts prepared
      by sequential extraction procedure from dried starfish found to be ineffective.
      This study paves the way for further investigation on the peptide composition in
      the PBS extract of the starfish to discover potential chemotherapeutic agents.

PMID- 23009984
TI  - Behavioral and neurochemical profile of some novel phenacyl based isonipecotamide
      derivatives.
AB  - Study of natural products led to the development of new molecules of potential
      biological activity. Piperidine nucleus constitutes one of the components of
      various alkaloids and drugs. During the course of our project regarding the
      synthesis of derivatives of piperidine carboxamide to study the effects of these
      compounds as anti-depressive agents, some of the compounds exhibited significant
      effects at all three doses, through open field activity thus establishing a
      direct relationship between dose and locomotion. Moreover, these compounds have
      also shown the decreased level of 5-HT alone with increased level of dopamine as
      an indication of their antagonism towards 5-HT receptor.

PMID- 23009985
TI  - Antimicrobial and anti-inflammatory activities of leaf extract of Valeriana
      wallichii DC.
AB  - Valeriana wallichii DC (Valerianaceae) is one of the most widely used traditional
      remedies for various complications associated with nervous system and digestion.
      No antimicrobial and anti-inflammatory studies have so far been carried out on
      the aerial parts of the plant. The present work was focused to evaluate the
      antimicrobial (antifungal and antibacterial) and anti-inflammatory properties of
      V. wallichii using reported methods. Chloroform fraction (VW-2) and hexane
      fraction (VW-3) exhibited significant activity against S. aureus and B. subtilus,
      respectively. The chloroform fraction (VW-2) showed significant activity against
      S. aureus with 0.27 mg/ml MIC, where 0.31 mg/ml MIC was deduced for VW-3 fraction
      against B. subtilus. VW-3 fraction was also found to be the most potent inhibitor
      of M. canis, showing 70% inhibition with an MIC value of 0.19 mg/ml. Considerable
      inhibitory activity was also observed for VW-2 and water fraction (VW-6) against
      M. canis and A. flavus. A remarkable anti-inflammatory like activity was observed
      for the crude extract at a dose of 200 mg/kg at all observed durations. Other
      doses of the sample also showed excellent activity. Looking to these results it
      may be concluded that V. wallichii may be a potential source for activity guided
      isolation of natural products with antimicrobial and anti-inflammatory-like
      properties.

PMID- 23009986
TI  - A new validated HPTLC method for quantitative determination of 1, 5
      dicaffeoylquinic acid in Inula crithmoides roots.
AB  - 1, 5-Dicaffeoylquinic acid (1, 5-DCQA), a potent HIV-1 integrase inhibitor, is
      currently undergoing an evaluation as a promising novel HIV therapeutic agent.
      This work aims at developing an accurate, rapid, repeatable and robust HPTLC
      method for the determination of 1, 5-DCQA in its natural sources. 1, 5-DCQA is
      the major component of the n-butanol fraction, the most biologically active
      hepatoprotective fraction, of Inula crithmoides roots extract. Thus, it will be
      of interest to evaluate the plant roots as a potential source of 1, 5-DCQA using
      a fully validated HPTLC method. The percentage of 1, 5-DCQA in the studied plant
      (0.035% w/w) was found to be approximately similar to those previously determined
      in other antioxidant herbal drugs, in which 1, 5- DCQA is the main phenolic
      constituent. The results obtained showed that the described HPTLC method is
      suitable for routine use in quality control of herbal raw material, extracts and
      pharmaceutical preparations containing 1, 5-DCQA. No HPTLC method has been
      reported in literature for the determination of 1, 5-DCQA in medicinal plants.

PMID- 23009987
TI  - Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin
      associated nephrotoxicity in rabbits.
AB  - Oxidative stress causes the generation of reactive oxygen species (ROS) that lead
      to nephrotoxicity. An aminoglycoside, gentamicin, has pronounced nephrotoxic
      effect in humans and animals and this study was planned to observe the nephro
      protective effect of antioxidants, vitamin C and Nigella sativa oil. Serum
      creatinine, blood urea nitrogen, and antioxidant activity were measured as
      indicators of nephrotoxicity for all the groups of rabbits. Results showed that
      vitamin C and Nigella sativa oil both had nephro-protective effect as they
      lowered the values of nephrotoxicity indicators (serum creatinine, blood urea
      nitrogen, and antioxidant activity) as compared to gentamicin control group
      values. When these two antioxidants were given as combination, they proved to
      have synergistic nephro-protective effect.

PMID- 23009988
TI  - Anti-inflammatory, anti-bacterial activity and structure-activity relationships
      of substitutions on 4-thiazolidinone derivatives - Part-1.
AB  - Environmentally benign and economically feasible procedures have been adopted for
      the synthesis of novel biologically potential 4-thiazolidinone derivatives.
      Purpose built microwave oven and ionic liquids (PTCs) showed wrack improvements
      in yield, time and cost. The yield of 1st series (01-08) obtained in the ranged
      from 82.4-94.2% and for 2nd series (09-16) obtained 80.6-92.8%. The compounds (01
      16) were applied for anti-inflammatory activity at concentrations of 0.5 and 01
      mg/kg in carrageenan induced acute and formalin induced chronic inflammatory
      procedures in mice and better results were obtained at 0.5 mg/kg dose. Some of
      the compounds 03, 04, 07, 12, 13 showed remarkable anti-inflammatory activity in
      both procedures as compared to the standard reference drug 2-(2,6-dichloranilino)
      phenyl acetic acid (diclofenac). Particularly compound 12 and 13 may be used as a
      non-steroidal anti-inflammatory drug (NSAID) to reduce inflammation. The
      compounds (01-16) were screened for their antimicrobial activity (in-vivo) and
      found that the compounds 12, 13 and 14 exhibited comparable or higher
      antibacterial activity then ciprofloxacin (standard) against E. coli, S.
      enteritidis, P. aeruginosa, S. aureus and B. subtilis. The compounds of series-2
      showed significant activity as compared with ciprofloxacin. These compounds could
      be lead to the selection and use as efficient antimicrobial agents, especially
      for the treatment of multi-drug resistant infections.

PMID- 23009989
TI  - Formulation and optimization of tramadol loaded alginate beads using response
      surface methodology.
AB  - Tramadol loaded alginate beads were formulated by ionic cross-linking technique
      employing calcium chloride as cross-linking agent. Several parameters like bead
      size, swelling index, incorporation efficiency, in vitro release and in vivo drug
      activity studies were investigated. Tramadol loading and concentration of calcium
      chloride were found to have a significant effect on the selected parameters.
      Tramadol release decreased with decreasing drug loading and increasing
      concentration of cross-linking agent. Kinetic modeling indicates the involvement
      of both swelling and erosion on the release characteristics of the drug from the
      beads. A 2 factors-3 levels central composite design (CCD) was employed to
      evaluate the effect of critical formulation variables, namely drug loading (X1)
      and concentration of calcium chloride (X2) on various responses. Multiple linear
      regression analysis generated polynomial mathematical models for various response
      variables and the corresponding response surface and contour plots were drawn. X1
      was found to have more significant effect than X2 on the dependent variables. In
      vivo drug activity studies of the alginate beads demonstrated significant
      antinociceptive effect of tramadol.

PMID- 23009990
TI  - Formulation development and investigation of ibuprofen controlled release tablets
      with hydrophilic polymers and the effect of co-excipients on drug release
      patterns.
AB  - The aim and objective of the present study was to formulate and evaluate
      controlled release polymeric tablets of ibuprofen with determinations of
      formulation factors using various grades and types of polymer ethocel i.e.
      ethocel standard 10P; 10FP, 100P and100FP for their release rates and release
      patterns in suitable media and also the mechanism involved in the release of drug
      from the matrices. The effect of several co-excipients was also studied on the
      drug release rates and patterns of Ibuprofen from the polymeric matrices.
      Ibuprofen-ethocel CR tablets were prepared at three different D: P ratios i.e.
      10:1, 10:2 and 10:3. The effects of co-excipients were studied only in
      formulations having D: P ratio of 10:3. In vitro drug release studies of
      ibuprofen-ethocel controlled release matrix tablets were carried out in phosphate
      buffer pH 6.8 using pharma test dissolution apparatus adopting rotating basket
      method according to USP. Different kinetic models were applied to the release
      data of test formulations in order to investigate the release mechanism of drug
      from the controlled release matrix tablets. The release patterns of ibuprofen
      ethocel CR matrices were compared with reference conventional ibuprofen tablets
      and ibuprofen SR tablets. F2 similarity factor was applied to the test
      formulations and reference standard to compare their similarities. The drug
      formulations studied exhibited satisfactory release results.

PMID- 23009991
TI  - Phytochemical screening and antimicrobial activity of Coccinia cordifolia L.
      plant.
AB  - The medicinal plant, Coccinia cordifolia L. was analyzed for its chemical
      composition. The antimicrobial activities of the methanol, water, ethanol and
      ethyl acetate extracts of Coccinia cordifolia L. plant were evaluated against
      some Gram positive bacteria (Sarcina lutea, Bacillus subtilis and Staphylococcus
      aureus), Gram negative bacteria (Salmonella typhi, Shigella dysenteriae and
      Escherichia coli) and fungi (Candida albicans, Aspergillus niger and Penicillium
      notatum). Chemical analysis showed that the plant is rich in nutrients,
      especially antioxidant compounds such as total phenol, vitamin C and beta
      carotene. Phytochemical screening showed that the methanolic extract contains the
      bioactive constituents such as tannins, saponins, phenols, flavonoids and
      terpenoids. In the methanolic extract of the plant, promising antimicrobial
      potential was observed against the tested microorganism. Methanolic extract
      showed highest activity against Shigella dysenteriae, Escherichia coli,
      Staphylococcus aureus, and Candida albicans compared to the other extracts. Water
      extract showed less antimicrobial activity as compared to other extractants.

PMID- 23009992
TI  - Human Pappilomavirus (HPV) induced cancers and prevention by immunization.
AB  - Incidences of different types of cancer are increasing in Pakistan, among which
      cancer of Cervix and Respiratory pappilomatosis are of great concern because of
      their association with human Pappilomavirus (HPV). Cervical cancers typically
      distress women of middle age or older; however it may affect women in any age
      after the puberty. Two serotypes of HPV (16 & 18) accounts 70% of cervical cancer
      cases, while HPV (6 & 11) are considered low-risk viruses associated with genital
      warts (Condyloma acuminata) and Respiratory pappilomatosis in both gender.
      Generally, there is transient role of HPV in human body and are removed by immune
      system in or around 1 year. Data from different Pakistani hospitals provides
      sound evidence for increasing trends of cervical cancer, which is, being
      developing country imperative for us. As the cost of cancer management is
      increasing day by day with poor survival rate and its burden is borne by patient,
      their family or society in-large, so if screening or prevention is possible then
      there would be need to identify target population for screening and vaccination.
      By quality adjusted life year (QALY) measurement, the data from different sources
      indicates that adolescent age is the appropriate target population and is cost
      effective for vaccination. Two vaccines manufactured by recombinant DNA
      technology are licensed in some parts of the world for prevention of HPV related
      cancers, however both have certain advantage over another, as one of the vaccines
      contains viral like proteins of two HPV serotypes 16 & 18 and provide additional
      cross protection against HPV type 13 and 45 with 100% seroprotection, while the
      other vaccine, being quadrivalent offers protection against four serotypes 6, 11,
      16 and 18. Both vaccines tolerability and safety profiles are similar and
      acceptable, however bivalent vaccine appears to provide long-lasting immunity by
      the development of memory B-cells hypothetically due to difference of adsorbing
      agent used by manufacturer, on the other hand, quadrivalent vaccine offers
      protection against cervical cancer but also offers additional protection against
      Condyloma acuminata and respiratory Pappilomatosis. As these vaccines are new in
      the market and initial trials indicate availability of antibodies for up to
      around 5 years i.e. why it is controversial at the moment that whether booster
      dose is recommended or not, however it is assumed that, there is no harm to have
      booster dose at 5th year of vaccination.

PMID- 23009993
TI  - Effect of compression pressure, preservative, and storage with potassium chloride
      on the microbiological quality of tablets formulated with Terminalia randii Gum
      (Combretaceae).
AB  - Gums are used as binders in tablets and also as emulsion stabilisers, suspending
      agents and thickeners in syrups. The need for other natural gums apart from the
      conventional gums to be employed as binding agents in tablets formulation led to
      this study. A gum obtained from the incised trunk of Terminalia randii
      (Combretaceae) was evaluated for the effect of compression pressure, methyl
      paraben preservative and storage with potassium chloride, on the microbial load
      of tablets formulated with the gum. The microbial load was determined by surface
      spread method on the processed gum at suitable dilutions, and tablets formulated
      from the gum at different compression pressures. The formulated tablets were
      evaluated for microbial load, also when stored in potassium chloride for 8 and 12
      weeks with and without preservation with 1% Methyl Paraben. In each case the
      compressed tablets were incubated in 0.1% peptone water as control. The microbial
      load recorded reflected generally, reduction in microbial counts in tablets
      formulated with the gum as a binder both in terms of compression at different
      pressures and when the different compression pressures were associated with or
      without 1% methyl paraben in the presence of potassium chloride. Comparatively,
      the processed gum showed higher microbial load than the pressure compressed
      tablets. Besides the different compression pressures, duration of storage was
      also found to cause reduction of microbial load, particularly in the formulated
      tablets compressed with methyl paraben stored in potassium chloride such that
      after 8 weeks, the microbial load was zero. The studies showed that compression
      pressures and duration of storage caused marked reduction in microbial load of
      the tablets formulated with the processed gum of Terminalia randii as a binder.

PMID- 23009995
TI  - Preparation and characterization of domperidone solid dispersions.
AB  - Domperidone is a highly water insoluble drug exhibiting poor dissolution pattern.
      The purpose of this work was to increase the dissolution rate of Domperidone by
      formation of solid dispersion with different water soluble carriers. Binary
      systems of Domperidone were prepared with polyvinyl pyrrolidone k-30 (PVP),
      poloxamer 188 (P188) and polyethylene glycol 6000 (PEG 6000) at different weight
      ratios using the solvent evaporation method, physical mixtures of the same
      systems were also used. The effect of the method of preparation was also
      investigated by preparing some selected formulations using melting method. As
      P188 is known to inhibit CYP3A4 enzyme which is responsible for hepatic
      metabolism of many drugs including Domperidone, the effect of incorporation of
      PVP or PEG 6000 as ternary component to P188 solid dispersion on dissolution rate
      was also investigated. Formulations were characterized by Fourier transform
      infrared (FTIR) and Differential scanning calorimetry (DSC). Drug content
      uniformity and dissolution rate were studied. Solid dispersions showed a better
      dissolution compared to the pure drug and physical mixtures, with PVP showing the
      highest dissolution efficiency. As indicated from DSC data, Domperidone was in
      the amorphous form, which confirmed the better dissolution rate of solid
      dispersions. Some ternary P188 combinations showed a better enhancement in drug
      dissolution compared to the optimized P188 binary system. This would present a
      potential of increasing oral bioavailability of Domperidone by increasing its
      dissolution rate and by inhibiting its pre-systemic metabolism by the presence of
      P188.

PMID- 23009994
TI  - Comparing the effects of salts of diclofenac and alminoprofen with aspirin on
      serum electrolytes, creatinine and urea levels in rabbits.
AB  - The effects of diclofenac sodium, diclofenac potassium, alminoprofen and aspirin
      on serum electrolytes (serum Na(+) and K(+)), urea and creatinine were compared
      in rabbits in acute and chronic phases of treatment. The data suggested that all
      the four drugs markedly increased the serum electrolytes, urea and creatinine
      levels in both post-treatment phases. In conclusion, present study does not
      present any advantage of diclofenac sodium over diclofenac potassium at
      electrolyte levels on short and long term treatment. Nevertheless, current data
      support the evidence of renal function impairment by all the four drug therapies
      used in the present study, which is generally caused by NSAIDS.

PMID- 23009996
TI  - Exploration of potential ligands against cancer-causing transcription factor
      E2F3.
AB  - The transcription factor-based therapeutic approaches are the mainstay of current
      anticancer drug design options to develop highly selective agents with novel
      modes of action. In this paper, a homology model of DNA-binding domain of
      transcription factor E2F3 was generated according to X-ray structure of E2F4. As
      a first step of our proposed project aspired towards exploration of highly
      selective potential E2F3 ligands, we performed structure-based virtual screening
      of ZINC 3D chemical database by using Dock Blaster server. Then 31 compounds,
      selected by filtration step, were docked against the prominent DNA binding site
      residues of E2F3 model. Two of them have shown a promising interaction with
      respect to binding poses. The aim is to propose new active ligands against
      neoplasias characterized by overexpression of E2F3 transcription factor.

PMID- 23009997
TI  - Biological activities of Eremostachys laevigata Bunge. grown in Iran.
AB  - Essential oil from flowers, stems, and roots of Eremostachys laevigata Bunge.
      gathered in Iran was analyzed using gas chromatography (GC) and gas
      chromatography/mass spectroscopy (GC/MS), and 23, 21, and 9 compounds were
      identified, respectively. The primary components of all three oils were found to
      be 1,8-cineole, benzaldehyde, and piperitenone oxide: 18.3%, 18.7%, and 2.5%;
      17.9%, 7.7%, and 63.3%; and 15.7%, 21.3%, and 1.2%, respectively. The oils
      derived from flowers and stems also contained cis-piperitone oxide as a major
      component (10.1% and 12.2%, respectively). E. laevigata oil showed antibacterial
      activity, particularly towards Gram-positive bacteria; additionally antioxidant
      activity was induced with IC(50) of flowers, stems and roots of E. laevigata
      (277.1, 495.0, and 212.6 MUg/ml), respectively. Furthermore, under beta-carotene
      linoleic acid test assay the flower, stem, and root oils of E. laevigata had a
      high antibacterial effect.

PMID- 23009998
TI  - Synthesis, characterization and biological screening of sulfonamides derived form
      2-phenylethylamine.
AB  - In the present study, a series of N-substituted derivatives of 2-phenylethylamine
      has been synthesized. The reaction of 2-phenylethylamine (1) with benzene
      sulfonyl chloride (2) yielded N-(2-phenylethyl) benzenesulfonamide (3), which
      further on treatment with alkyl/acyl halides (4a-i) in the presence of sodium
      hydride furnished into N-substituted sulfonamides (5a-i).  These derivatives were
      characterized by IR, (1)H-NMR and EI-MS and then screened against acetyl
      cholinesterase (AChE), butyryl cholinesterase (BChE) and lipoxygenase enzyme
      (LOX)  and were found to be potent inhibitors of butyryl cholinesterase only.

PMID- 23009999
TI  - Impact of chitosan as a disintegrant on the bioavailability of furosemide
      tablets: in vitro evaluation and in vivo simulation of novel formulations.
AB  - To determine the effect of chitosan, starch powder, polyvinylpyrrolidone (PVP),
      Avicel PH 101 powder, Avicel PH 102 granules as a function of different
      concentrations on the solubility, disintegration and hence dissolution of
      furosemide from immediate release tablet dosage forms. The tablets were prepared
      by the wet granulation method and evaluated for hardness, friability,
      disintegration and in vitro dissolution. Chitosan 7% w/w showed the fastest
      disintegration of furosemide tablets among the other disintegrants studied. This
      was attributed to its highest swelling properties and velocity constant of water
      uptake. The step of adding chitosan during tablet preparation had a great effect
      on the physical properties and dissolution profiles of the prepared tablets with
      external addition of chitosan showed best results compared to  best results
      comparing to internal-external or internal addition. The most appropriate force
      of compression was 4ton/cm(2). The selected formula F15 containing 7% w/w
      chitosan was successful and showed a high significant (p<0.001) enhancement in
      disintegration and dissolution behaviors of furosemide tablets in comparison with
      the commercially available Furosemide (r) tablets. These results were supported
      by the simulated data where F15 formula showed the highest plasma concentration C
      max 1.89mcg/mL after 0.5 hr compared to C-max 1.05mcg/mL after 1hr for the
      reference. The present study demonstrated that chitosan is a very good candidate
      to be used as a tablet disintegrant and was able to enhance the dissolution of
      poorly absorbable drugs.

PMID- 23010000
TI  - Quantification of sparfloxacin in pharmaceutical dosages and biological samples.
AB  - A simple and fast method for spectrophotometric determination of sparfloxacin
      using p-dimethyl-aminobenzaldehyde (DMAB) has been developed.  A yellow coloured
      product formed from reaction between sparfloxacin and DMAB as a result of
      condensation reaction at room temperature. The maximum absorbance was found at
      392 nm with molar absorptivity of 4.9 * 10(3) L mol(-1) cm(-1). All parameters
      for the reaction, as concentration of DMBA reagent, molarity of sulphuric acid,
      and reaction temperature were studied. Under the conditions studied, a linear
      relationship between absorbance of the condensation product and concentration of
      sparfloxacin in the range of 2.0-80.0 MUg mL(-1) was found with good correlation
      coefficient (0.9997). The limits of detection (LOD) and quantification (LOQ) for
      the proposed method were found to be 0.22 and 0.75 MUg mL(-1) respectively. The
      repeatability and accuracy (model) of the method was studied at three different
      concentrations of sparfloxacin and found with value of relative standard
      deviation less than 2.0%. The method was found selective for determination of
      sparfloxacin in the presence of commonly used excipients in dosage forms. The
      developed method was validated statistically and applied successfully to the
      analysis of the drug in pure form, pharmaceutical preparations, and spiked blood
      plasma and urine samples with good accuracy (real) and precision. The percentage
      recovery was found from 99.0-100.0% with relative standard deviation less than
      1%. The results of the proposed method were compared statistically with the
      results of literature HPLC method.

PMID- 23010001
TI  - Cytotoxicity evaluation of vancomycin and its complex with beta-cyclodextrin on
      human glial cell line.
AB  - The possible cytotoxic effects of vancomycin and its complex with beta
      cyclodextrin (beta-CD) on human glial cell line (CRL 8621) were studied
      accordingly by means of MTS assay. The cultured cells were incubated with various
      concentrations of vancomycin, beta-CD as well as beta-CD/vancomycin complex
      ranging from 4.69 to 300 ug/ml. A linear dose-dependency cytotoxicity followed by
      hermetic-like biphasic dose-dependence was observed after incubation period of 72
      hours. In general, significant increase (p<0.001) of cell proliferation was
      observed at lower concentrations: <18.75 MUg/ml for cells treated with beta-CD
      and their complex while < 9.38 MUg/ml for cells treated with vancomycin. In
      contrary, regardless of the treatments given, significant (p<0.001) reduce in
      cell survival was found at higher concentrations >150 MUg/ml. In particular, 50 %
      inhibitory in vitro was achieved at the concentrations of 115.95 MUg/ml (for beta
      CD), 116.48 MUg/ml (for vancomycin) and 115.44 MUg/ml (for beta-CD/vancomycin
      complex).

PMID- 23010002
TI  - Anti-microbial activities of sulfonamides using disc diffusion method.
AB  - Sulfonamides, being the member of the oldest anti-microbial group of compounds
      possess wide anti-microbial activities and are effective against pathogenic
      strains of gram-positive and gram-negative bacteria. They are widely used in the
      treatment of various infectious diseases e.g. malaria, urinary tract infections,
      respiratory tract infections etc. Based on their effectiveness against most of
      the bacteria, two novel sulfonamides (N-(2-methoxy phenyl)-4
      methylbenzenesulfonamide and N-ethyl-4-methyl-N-(3-methyl
      phenyl)benzenesulfonamide) were synthesized. The compounds were characterized by
      FT-IR and elemental analyzer. Their anti-microbial activity was assessed and
      observed against gram-positive and gram-negative bacteria using disc diffusion
      method. They showed good anti-microbial activities.

PMID- 23010003
TI  - The role of zinc on anti-Newcastle disease virus specific antibody response and
      agranulocytes count in rabbits treated with methotrexate and prednisolone.
AB  - Zinc (Zn) plays a pivotal role in highly proliferative tissues including immune
      system. The long-term therapy of neoplastic and autoimmune disorders is
      associated with immunosuppression and myleosuppression. In the current study role
      of Zn on anti-Newcastle disease virus response and agranulocytes count of
      methotrexate and prednisolone treated rabbits. Thirty six healthy rabbits were
      randomly segregated into six groups (group I to VI) each containing six rabbits.
      Oil based Newcastle disease virus (NDV) vaccine was administered subcutaneously
      to rabbits of all the groups at day 0 and 21  and after one week, all the groups
      received Zn, (Zn + prednisolone), prednisolone, (Zn + methotrexate) methotrexate
      orally from day 7 to day 21, except the control. The serum antibody titer, total
      and differential leukocyte count were measured weekly for 6 weeks. The
      administration of zinc in combination with methotrexate showed same antibody
      titer as that of the control suggesting that Zn has ability to counteract the
      methotrexate-induced immunosuppression. However, Zn did not show any significant
      impact in combination with prednisolone (p<0.05). The results of the present
      study indicate that co-administration of Zn and methotrexate is beneficial in the
      activity of immune system.

PMID- 23010004
TI  - In vitro hemolytic effect of sulfadoxine/pyrimethamine and
      artemether/lumefantrine on malaria parasitized erythrocytes of female patients.
AB  - G6PD is an X-linked gene enzyme that protects erythrocytes from hemolysis when
      they are exposed to antimalarial drugs because of the effects of the free
      radicals generated by these drugs. We investigated the effects of Fansidar TM
      (Sulfatoxine/Pyrimethamine) and Coartem TM (Artemether/Lumefantrine) on the
      hemolysis of malaria parasitized female erythrocytes. Twelve (12) malarious
      patients attending the University of Benin Teaching Hospital, Benin City,
      Nigeria, were used in this study. Ten (10) apparently healthy female students
      from the Medical School, University of Benin, acted as control. Low, normal (the
      recommended adult dose) and high doses of Fansidar TM and Coartem TM were used to
      determine the percentage hemolysis by checking the absorbance of the various
      samples. Data was analyzed by the Student's t-test and ANOVA with p<0.05
      indicating the level of significance. At low doses of Fansidar TM and Coartem TM,
      no hemolysis occurred, while at normal doses, Fansidar TM showed no hemolysis but
      significant hemolysis (p<0.05) was observed in the Coartem TM group. At high
      doses, both FansidarTM and CoartemTM caused significant (p<0.05) hemolysis. High
      doses of both drugs and normal dose of CoartemTM caused significant hemolysis.
      There was no hemolysis observed in the normal dose of FansidarTM and low doses
      for both drugs, similar to the trend reported for male subjects.

PMID- 23010005
TI  - Role of electrolytes disturbances and Na(+)-K(+)-ATPase in cisplatin - induced
      renal toxicity and effects of ethanolic extract of Cichorium intybus.
AB  - Cisplatin is known by its toxicity by disturbing electrolytes homeostasis. Thus
      we aimed to find out the role of herbal plant Cichorium intybus on Cisplatin -
      induced toxicity. 24 male Albino Wistar rats were randomly divided into 4 groups:
      Group I is termed as untreated control; Group II is Cisplatin control and
      received 3 mg/ kg b.w.; i.p.; Group III received C. intybus ethanolic extract at
      a dose of 500 mg/kg b.w. orally for 10 consecutive days and Group IV is Cisplatin
      + C. intybus pretreated group.  C. intybus is given 30 minutes prior to
      Cisplatin. Cisplatin - induced electrolytes disturbances is indicated by increase
      Intra - erythrocyte sodium content, decreased plasma magnesium, calcium and Intra
      erythrocyte Na(+)-K(+)-ATPase which implicates the renal toxicity. At a dose of
      500 mg/kg b.w. of C. Intybus pretreatment showed partial counter action on the
      electrolytes imbalances and Na(+)-K(+)-ATPase activity.

PMID- 23010006
TI  - Report: Platelet aggregation inhibition activity of selected legumes of Pakistan.
AB  - The current study was designed to explore the platelet aggregation activity of
      methanolic extracts of green gram, lentil, mash bean and soya bean. The extracts
      dose-dependently inhibited platelet aggregation initiated by arachidonic acid
      (AA) and platelet activating factor (PAF). Extract of green gram was effective
      only against AA mediated activity while mash bean and soya bean extracts were
      effective against both AA and PAF mediated activity. But lentil extract has no
      activity. The order of activity based on IC(50) value is, Mash bean > Soya bean >
      Green gram. This preliminary result suggests that legume seed extract may be
      taken as a candidate lead natural compound to be considered in the search for
      natural products with beneficial effects on aberrant platelet activation mediated
      cardiovascular disorders.

PMID- 23010007
TI  - Formulation and evaluation of herbal anti-acne moisturizer.
AB  - The moisture content present in human skin makes it look young and the use of
      moisturizer results in fastening the moisture with a surface film of oil. Acne
      vulgaris is one of the most commonly seen diseases among the youth. The present
      study is focused on the use of herbs as moisturizer for acne treatment. The anti
      acne moisturizer was formulated from herbal crude extracts and investigated the
      physico-chemical parameters as well as antibacterial activity of the formulation.
      The study revealed that ethanol extract of Andrographis paniculata, Glycyrrhiza
      glabra, Ocimum sanctum, Azadiracta indica and Green tea possessed the potential
      for inhibiting acne. It was observed that the optimal formula of anti-acne
      moisturizer was satisfactorily effective to control acne inducing bacteria i.e.,
      Staphylococcus epidermis and Propionibacterium. The physico-chemical parameters
      of the formulation were also optimal with no signs of irritation.

PMID- 23010008
TI  - Report: Comprehensive nutrients analysis of rhizomes of Polygonatum
      verticillatum.
AB  - The current study was undertaken to estimate the concentration of micronutrients
      (Zn, Fe, Pb, Cu, Ni, Cd, Cr, Co, Sb and Mn), macronutrients (Na, Ca and K) and
      essential life nutrients (proteins, fats, carbohydrates and ascorbic acid) along
      with ash, fiber and moisture contents. Atomic absorption spectrophotometer was
      employed for the analysis of micronutrients while flame photometry for
      macronutrients. For proximate analysis (proteins, fats, carbohydrates, ash,
      fibers and moisture), Association of Official Analytical Chemists methods (AOAC)
      were used and titration method for ascorbic acid determination. It is evident
      from the results that the crude extract and its fractions accumulate significant
      concentrations of both micro and macro nutrients. The significant quantities of
      essential life nutrients like proteins, fats, carbohydrates and ascorbic acid
      along with ash, fiber and moisture contents were also found in extracts. It is
      concluded that the extracts of rhizomes accumulated significant quantities of
      life indispensible nutrients and validated the ethnobotanical uses of the plant
      as tonic and energizer.

PMID- 23010009
TI  - Emergence of resistance to fluoroquinolones among gram positive and gram negative
      clinical isolates.
AB  - Fluoroquinolones are broad-spectrum antibiotics that are considered as first line
      drugs to treat infectious diseases. In order to find out useful fluoroquinolones,
      the antibiotic resistance of fluoroquinolones, namely, ofloxacin (OFL),
      ciprofloxacin (CIP), norfloxacin (NRF), enoxacin (ENX), pefloxacin (PFL) and
      levofloxacin (LVF) was investigated against ninety five clinical isolates that
      includes Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and
      Proteus mirabilis. In vitro activity of these isolates was carried out by agar
      dilution method. All Staphylococcus aureus were sensitive to OFL at 2 MUg/ml.
      About 6% isolates of Klebsiella pneumoniae were found to be resistance to LVF and
      ENX, 6% to CIP, OFL and PFL and none of the isolates were resistant to LVF and
      ENX. Percentage resistance of P. aeruginosa was found to be 4.35% to CIP, 7% to
      OFL and 2.2% to NRF, whereas 8.69% to ENX, 0% to PFL and 17.4% to LVF,
      respectively. The present study provides the data about the emergence of
      resistance to fluoroquinolones among gram positive and gram negative bacteria and
      strongly recommends the rational and appropriate use of these antibiotics.

PMID- 23010010
TI  - Study of the effects of BaCl(2) on the level of glutathione in plasma and
      cytosolic fraction in whole blood.
AB  - Barium has important role in the field of medical sciences, but it has been found
      in various studies that barium can cause numerous toxic effects. Studies have
      proven the strong affinity of the metalloelements for the sulfhydryl group (SH),
      present in reduced glutathione (GSH) and other biological molecules. In this
      context, the study about the possible interaction of BaCl(2) with glutathione in
      whole blood components was of interest, as an indication about the extent of
      barium toxicity and the role of glutathione in the conjugation and detoxification
      of the metalloelement barium. The concentration dependent and time dependent
      effect of BaCl(2) on the level of GSH in plasma and cytosolic fraction in whole
      blood was investigated, following Ellman's method. It was found that BaCl(2)
      causes a decrease in the GSH level, which is more pronounced with increasing
      concentration of BaCl(2) and with time incubation as well. The observed effect
      GSH concentration may be presumably due to production of oxidized glutathione
      (GSSG) or then due to barium-glutathione (GS-Ba-SG) conjugate formation.

PMID- 23010011
TI  - Mining of protein based biomarkers for type 2 diabetes mellitus.
AB  - Diabetes mellitus in general and Type 2 Diabetes (T2D) in particular, are very
      complex diseases with heterogeneous etiology. T2D results from the impaired
      secretion or action of the insulin with a clinical phenotype of persistent
      hyperglycemia in the uncontrolled subjects. The disease clinical features appear
      after several years of latent preclinical asymptomatic conditions. Thus, when the
      disease is full blown, there are limited chances to reverse the disease
      phenotype; however, it can be managed by controlling diet, changing life style
      and using medicines. Understanding pathological mechanisms whereby genetic and/or
      environmental factors contribute to the development of diabetes is important for
      the prevention and treatment of the disease. In this regard, approaches such as
      genomics, transcriptomics, proteomics and metabolomics are being applied to
      identify more specific biomarkers for T2D for its early detection, management and
      devising new therapies. The emphasis of the present review is to provide updates
      on the applications of proteomics in addressing T2D with a focus on protein based
      biomarker discovery. Moreover, the idea of personalized medicine and intervention
      is also discussed for diabetes treatment in proteomics perspective.

PMID- 23010012
TI  - An Assessment of nutrition education in selected counties in New York State
      elementary schools (kindergarten through fifth grade).
AB  - OBJECTIVE: To assess the extent to which nutrition education is implemented in
      selected counties in New York State elementary schools (kindergarten through
      fifth grade) and explore how nutrition knowledge is presented in the classroom
      and what factors support it. DESIGN: Cross-sectional, self-administered survey.
      SETTING: New York State elementary schools in selected counties. PARTICIPANTS:
      New York State elementary school teachers (n = 137). MAIN OUTCOME MEASURES: Hours
      spent teaching nutrition; nutrition topics, methods of teaching, education
      resources, and aspects of the school environment that may influence nutrition
      education. ANALYSIS: Crosstabs with a chi-square statistic and ANOVA. RESULTS:
      Eighty-three percent of teachers taught some nutrition (9.0 +/- 10.5 hours)
      during the academic year. Teachers taught lessons about finding and choosing
      healthy food (61%), relationship between diet and health (54%), and MyPyramid
      (52%) most often. Suburban teachers (12.4 +/- 12.5 hours) taught significantly (P
      = .006) more hours of nutrition than rural teachers (4.2 +/- 3.9 hours). Teachers
      at schools with fewer than 80% nonwhite students taught significantly (P = .02)
      more (10.4 +/- 11.4 hours) compared to schools with greater than 80% nonwhite
      students (5.6 +/- 6.4 hours). CONCLUSIONS AND IMPLICATIONS: Teachers reported
      that nutrition education is important and that they are willing to teach
      nutrition. Efforts should be made that support integrated nutrition topics,
      methods of instruction, and availability of resources.

PMID- 23010013
TI  - Nutrition claims influence health perceptions and taste preferences in fourth-
      and fifth-grade children.
AB  - OBJECTIVE: To determine whether children perceive food with nutrition claims as
      healthier and tasting differently than those without claims. METHODS: Fourth- and
      fifth-graders (n = 47) from 3 California schools participated. Two identical
      products (cookies, crackers, or juice) were placed in front of product packages,
      1 with a nutrition claim, the other without. Each child was asked which product
      was healthier and which tasted better. RESULTS: The percentage of children who
      identified the reduced-fat cookie, whole-grain cracker, or 100% juice as
      healthier was 81%, 83% and 81%, respectively. The taste of the "healthier"
      product (ie, with nutrition claim) was preferred by 72%, 67%, and 54%,
      respectively. CONCLUSIONS AND IMPLICATIONS: A convenience sample of children
      perceived products with a nutrition claim as healthier and identified the
      "healthier" cookies and crackers as tasting better. Future research should
      examine whether food labeling can be used to encourage children to consume
      healthier diets.

PMID- 23010014
TI  - The healthy toddlers curriculum.

PMID- 23010015
TI  - Sensitive immunosensor for the label-free determination of tumor marker based on
      carbon nanotubes/mesoporous silica and graphene modified electrode.
AB  - A novel label-free immunoassay strategy for sensitive detection of alpha
      fetoprotein (AFP) was proposed based on controlled fabrication of single-wall
      carbon nanotubes (CNTs) inside the channels of mesoporous silica (MPS). The
      silanol groups on the internal pore walls of MPS were grafted with amino groups,
      while the silanol groups on the external surface were blocked by
      trimethylchlorosilane (TMCS). Thus, CNTs and the monoclonal antibodies of AFP
      (anti-AFP) could be confined inside the mesopores of MPS by the covalent linking
      of the carboxyl and amino groups. For the preparation of immunosensing electrode,
      graphene sheets (GS) and anti-AFP/CNTs/TMCS-MPS were coated on the electrode
      surface based on layer by layer assembly. After dipping the anti-AFP/CNTs/TMCS
      MPS/GS/GCE into the sample solution, the immunoconjugates formed after the
      immunological reaction, which resulted in the increment of spatial blocking and
      impedance of the immunosensing interface. Thus, the peak current decreased with
      the increasing concentration of AFP. CNTs inside the mesopores could promote the
      electron transportation through the pore channel. Meanwhile, modified GS with
      distinctive conduction capacity could also improve the electrochemical response.
      Under the optimal experimental conditions, the label-free immunosensor could
      detect AFP in a linear range from 0.1 to 100 ng mL(-1) with a detection limit of
      0.06 ng mL(-1) (3sigma).

PMID- 23010016
TI  - Microfluidic reflectometric interference spectroscopy-based sensing for
      exploration of protein-protein interaction conditions.
AB  - A microfluidic reflectometric interference spectroscopy (RIfS) system was adopted
      for the investigation of protein-protein interaction (PPI). The influence of
      reaction conditions (pH and temperature) on the antigen-antibody reaction of
      alpha-fetoprotein (AFP) and its monoclonal antibody (anti-AFP) as a model of PPI
      was investigated in real time with a label-free fusion, where anti-AFP was
      covalently immobilized on the carboxylated silicon nitride sensor chips via amide
      bonds. Optimal pH and temperature were rapidly found by successive and alternate
      injections of AFP and the regeneration solution (glycine-HCl, pH 1.5) onto the
      anti-AFP immobilized sensor chip. The resultant optimized reaction conditions (30
      degrees C, pH 5.0) gave a 10 times higher detection limit, compared with the
      response under the commonly employed conditions (25 degrees C, pH 7.4). The
      proposed system was revealed to provide rapid tracking response against the
      change in temperature and pH. Consequently, the proposed RIfS system has a
      potential for the effective tool towards PPI analyses.

PMID- 23010017
TI  - In with the old and out with the new.

PMID- 23010018
TI  - Risk factors for the development of locoregional cutaneous metastases as the sole
      form of recurrence in patients with melanoma.
AB  - BACKGROUND: While locoregional cutaneous metastases (in transit and satellite) in
      melanoma have received little attention from researchers to date, they have
      pathogenic and prognostic features that distinguish them from other forms of
      locoregional recurrence. Identifying predictors of these metastases would be of
      great value for their prevention, early diagnosis, and treatment. The aim of this
      study was to identify the risk factors associated with locoregional cutaneous
      metastases as the first form of recurrence in the metastatic progression of
      melanoma. MATERIAL AND METHODS: Between 2000 and 2010, we prospectively collected
      the data of 1327 patients diagnosed with stage I and II melanoma. During follow
      up, 112 patients (8.4%) developed metastases. Of these, 36 had exclusively
      locoregional cutaneous metastases. The clinical and histological characteristics
      of this subgroup were evaluated. RESULTS: In the univariate analysis, significant
      predictors were patient age, primary tumor thickness, site, ulceration, mitotic
      index, and histological type. After multivariate analysis, the independent risk
      factors were tumor thickness (risk ratio [RR] 5.6; 95% CI: 2.7-11.5) and the
      location of the primary tumor on the lower limbs (RR 3.4; 95% CI: 1.0-11.5), on
      the head or neck (RR 4.8; 95% IC: 1.7-13.5), or in acral sites (RR 6.7; 95% IC:
      2.2-20.8). CONCLUSION: Patients who have melanomas with a Breslow thickness of
      more than 2mm located on the lower limbs, head, neck, or acral sites have a
      higher risk of developing locoregional cutaneous metastases. These findings could
      be useful in the design of future guidelines for the monitoring and management of
      melanoma.

PMID- 23010019
TI  - Activity of glucose oxidase immobilized onto Fe3+ attached hydroxypropyl
      methylcellulose films.
AB  - Hydroxypropyl methylcellulose (HMPC) insoluble films were prepared by (60)Co
      gamma irradiation of 10% (w/w) aqueous solutions of hydroxypropyl
      methylcellulose. The adsorption of Fe(3+) onto HPMC films was studied in the
      range of pH 3.0-7.0. The effect of initial concentrations of Fe(3+) solutions on
      adsorption capacity was studied in the range of 100-1000 ppm. Maximum adsorption
      capacity was found as 250 mg Fe(3+)/g dry HPMC film at pH 5.0. The structure and
      the morphology of Fe(3+)-attached HPMC film were evaluated by using FTIR/ATR and
      SEM-EDX methods. Glucose oxidase (GOX) immobilization on both pristine HPMC and
      maximum Fe(3+)-attached HPMC film was investigated in aqueous solutions
      containing different amount of GOX and at different pHs. Maximum GOX adsorption
      capacity was found as 500 mg/g Fe(3+)-attached HPMC film. Residual activity of
      GOX on pristine HPMC and Fe(3+)-attached HPMC films was investigated with
      changing pH. While maximum residual GOX activity was observed at pH 6.0 for free
      enzyme, it was obtained by HPMC and Fe(3+)-attached HPMC at pH 7.0. GOX
      desorption studies were achieved by using pH 6.0 buffer (I=0.02 M) and 0.1 M EDTA
      solutions. The long-term stability and activity studies of GOX, which is
      immobilized onto Fe(3+)-attached HPMC films are still under our investigation.

PMID- 23010020
TI  - Filtration, adsorption and immunodetection of virus using polyelectrolyte
      multilayer-modified paper.
AB  - A new method for detection of viruses has been developed. The entire assay can be
      performed within 2h, and consists of a polyelectrolyte-multilayer-modified
      cellulosic filter paper combined with immunodetection. The M13 bacteriophage was
      used as a model virus. A visual colour-based detection system, anti-M13
      horseradish peroxidase (HRP) conjugate and 3,3',5,5'-tetramethylbenzidine (TMB),
      was selected to allow semi-quantitative assessment by human eye, or quantitative
      assessment using a digital scanner. By filtering a volume of 0.50 ml, it was
      possible to visually detect a concentration of 10(6) pfu/ml. The detection limit
      was improved to 5*10(4) pfu/ml by increasing the volume of the sample to 100ml.
      For comparison, it was only possible to detect a concentration of 10(7) pfu/ml
      using conventional sandwich enzyme-linked immunosorbent assay (ELISA) with the
      same detection system.

PMID- 23010021
TI  - A facile one-pot solvothermal method to produce superparamagnetic graphene-Fe3O4
      nanocomposite and its application in the removal of dye from aqueous solution.
AB  - A superparamagnetic graphene-Fe(3)O(4) nanocomposite (G/Fe(3)O(4)) was
      synthesized by a facile one-pot solvothermal method. The nanocomposite
      G/Fe(3)O(4) prepared by the new method was firstly used as an adsorbent to remove
      dye for water pollution remediation. In comparison with G/Fe(3)O(4) prepared by
      the in situ chemical coprecipitation, the newly prepared G/Fe(3)O(4) had a higher
      adsorption efficiency for the dye. The adsorption characteristics of the
      nanocomposite adsorbent were examined using the organic dye pararosaniline as the
      adsorbate. The adsorption kinetics, adsorption capacity of the adsorbent, and the
      effect of the adsorbent dosage and solution pH on the removal efficiency of
      pararosaniline were investigated. The adsorption capacity of G/Fe(3)O(4) for
      pararosaniline was evaluated using the Freundlich and Langmuir adsorption
      isotherm models. The G/Fe(3)O(4) hybrid composite can be easily manipulated in
      magnetic field for desired separation, leading to an easy removal of the dye from
      polluted water. The G/Fe(3)O(4) hybrid composite would have a great potential in
      removing organic dyes from polluted water.

PMID- 23010022
TI  - Colloidal formulations of etoposide based on poly(butyl cyanoacrylate)
      nanoparticles: preparation, physicochemical properties and cytotoxicity.
AB  - This article describes the preparation, physicochemical characterization and
      cytotoxicity assessment of novel colloidal formulations of etoposide based on
      poly(butyl cyanoacrylate) nanoparticles. Nanoparticles were prepared by
      controlled emulsion polymerization of butyl cyanoacrylate in aqueous medium using
      two different non-ionic colloidal stabilizers (pluronic F68 and polysorbate 80).
      The nanoparticles were spherical in shape, with average size ranging from 110-150
      nm (empty nanoparticles) to 170-260 nm (drug-loaded nanoparticles), monomodal
      size distributions, and negative zeta-potentials at pH 7.4. Drug loading
      efficiency was around 63-68%. More than 80% of the drug was released from the
      formulations within 6-7h of dialysis experiments. Pluronic-coated nanoparticles
      possessed lower magnitude of the zeta-potentials (around -4 mV) in comparison
      with the polysorbate-coated ones (around -12 mV). All tested etoposide
      formulations induced apoptosis in adenocarcinoma human epithelial (A549) cells,
      as evident from condensation of chromatin and fragmentation of nuclei. It was
      found that etoposide formulated with poly(butyl cyanoacrylate) nanoparticles and
      polysorbate 80 exhibited the highest cytotoxicity toward adenocarcinoma cells.

PMID- 23010023
TI  - Development of amphiphilic, enzymatically-degradable PEG-peptide conjugate as
      cell crosslinker for spheroid formation.
AB  - In this study, we developed a novel kind of PEG-peptide conjugated cell
      crosslinker which is composed of amphiphilic oleyl-polyethylene glycol (PEG)
      derivatives conjugated with an enzymatically degradable peptide. The oleyl groups
      at both ends of the polymer chain act as anchoring moiety which can incorporate
      into cell membrane bilayer via hydrophobic interaction while the incorporation of
      the peptide sequence in the polymer chain renders the cell crosslinker
      enzymatically degradable. The average molecular weight, critical micelle
      concentration of the crosslinker was systematically characterized by gel
      permeation chromatography, fluorescence method and the crosslinker was shown to
      be readily cleaved by collagenase. HepG2 cells spheroids formation was observed
      when the cell crosslinker was added. The number of cells kept increasing over the
      culture period in the presence of cell crosslinker, suggesting its improved
      cytocompatibility. With the addition of cell crosslinker, the liver-specific
      functions of HepG2, such as ammonia elimination, albumin secretion, was enhanced
      by 1.9 times and 3.0 times on 7th day culture, respectively. Fluorescence
      microscopy showed more distinct and intense albumin staining in spheroids with
      cell crosslinker than that without crosslinker. This novel kind of cell
      crosslinker will be a promising material for tissue engineering and regenerative
      medicine.

PMID- 23010024
TI  - Effects of particle morphology, pore size and surface coating of mesoporous
      silica on Naproxen dissolution rate enhancement.
AB  - Naproxen (Nap) is a commonly used drug for antiphlogosis and analgesia, but its
      dissolution rate in water is quite low. In this work, the dissolution behavior of
      Nap after loading in mesoporous silica materials was investigated in a simulated
      intestinal fluid (pH=6.8). The results indicated that the pore sizes,
      morphologies and surface chemical groups of the mesoporous silica were
      significant factors on the dissolution behavior of Nap. The physical state of
      encapsulated Nap was affected by the pore sizes of mesoporous silica, which
      influenced its dissolution rate. Amorphous Nap exhibited a higher dissolution
      rate than crystallized Nap, even though the larger pore size could facilitate its
      diffusion from the matrix. The effect of the morphology of mesoporous silicas on
      the dissolution of Nap can be ascribed to the length of pore channels, that the
      longer channel showed a longer diffusion pathway of Nap. Moreover, the release
      rate of Nap from functionalized mesoporous materials was effectively controlled
      compared with that of unmodified materials.

PMID- 23010025
TI  - Complexation of HIV derived peptides with carbosilane dendrimers.
AB  - Dendrimers have been proposed as new carriers for selected HIV-1 peptides. This
      paper reports on the complexation behaviour of the three HIV-derived-peptides:
      Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef,
      NHGMDDPEREVLEWRFDSRLAF-COOH with second generation cationic carbosilane
      dendrimers (CBD) branched with carbonsilicon bonds (CBD-CS) or oxygensilicon
      bonds (CBD-OS). Studies on the formation of complexes between HIV peptides and
      CBDs by fluorescence polarization, zeta-potential, electrophoresis and
      transmission electron microscopy have shown that both studied dendrimers form
      complexes with HIV peptides. At a molar ratio of (2.5-3):1 (dendrimer:peptide),
      the complexes formed were in the size range of 180-275 nm and with significant
      positive surface charge. The results suggest that interactions between dendrimers
      and HIV peptides have electrostatic nature due to the negative charge of peptides
      backbone and positive charge of dendrimer functional groups. Dendriplex stability
      depended on the type of studied dendrimers. Time of peptides release from the
      complexes ranged from 1 (CBD-OS) to ~36 (CBD-CS)h. Basing on the obtained
      results, we propose that the water-soluble cationic carbosilane dendrimers can be
      considered for delivery of HIV peptides to dendritic cells.

PMID- 23010026
TI  - Structural characterization and antimicrobial properties of silver nanoparticles
      prepared by inverse microemulsion method.
AB  - Silver nanoparticles have been synthesized in the inverse microemulsions formed
      using three different surfactants viz., cetyl-trimethyl ammonium bromide (CTAB),
      Tergitol and Triton X-100. We have done a systematic study of the effect of the
      surfactants on the particle size and properties of the silver nanoparticles.
      Microscopic studies show the formation of spheres, cubes and discs shaped silver
      nanostructures with the size in the range from 8 to 40 nm. Surface plasmon
      resonance (SPR) peak was observed around 400 nm and 500 nm. In addition to SPR
      some extra peaks have also been observed due to the formation of silver metal
      clusters. The surface area increases from 3.45 to 15.06 m(2)/g with decreasing
      the size of silver nanoparticles (40-8 nm). To investigate the antimicrobial
      activity of silver nanoparticles, the nanoparticles were tested against the
      yeast, Candida albicans and the bacterium, E. coli. The results suggest very good
      antimicrobial activity of the silver nanoparticles against the test microbes. The
      mode of action of the antimicrobial activity was also proposed.

PMID- 23010027
TI  - Thermosensitive poly(N-isopropylacrylamide-co-glycidyl methacrylate) microgels
      for controlled drug release.
AB  - A new type of thermosensitive microgels with epoxy functional groups is designed
      and synthesized for drug delivery. The thermosensitive poly(N-isopropylacrylamide
      co-glycidyl methacrylate) (designated as P(NIPAM-co-GMA)) microgels are prepared
      by an emulsifier-free emulsion polymerization method and the chemical composition
      of the copolymer is determined by Fourier transform infrared spectroscopy (FTIR)
      and nuclear magnetic resonance ((1)H NMR). The lower critical solution
      temperature (LCST) of the microgels is 32 degrees C based on the transmittance
      changes at 500 nm monitored by UV/visible spectrophotometry. The hydrodynamic
      diameter and morphology of the microgel particles are examined by dynamic light
      scattering (DLS) and scanning electron microscopy (SEM), respectively. The drug
      release properties determined using 5-FU as the drug model in vitro reveal
      temperature dependence and low cytotoxicity. The thermosensitive microgels have
      large potential as targeted anti-cancer drug carriers.

PMID- 23010028
TI  - Physicochemical characterization of a monorhamnolipid secreted by Pseudomonas
      aeruginosa MA01 in aqueous media. An experimental and molecular dynamics study.
AB  - Given the increasing interest in the characterization of new biosurfactants, in
      this work we have carried out a physicochemical study of a monorhamnolipid
      (monoRL) produced by Pseudomonas aeruginosa MA01 in aqueous media. The detailed
      knowledge of the physicochemical properties of these monoRL biosurfactant is of
      importance for the validation of this particular P. aeruginosa strain as a useful
      biosurfactant producer. A pKa value for monoRL of 5.9 was consistently obtained,
      as well as the indication that the presence of one or two rhamnose rings does not
      have a notorious influence on the pKa of the carboxyl group. The critical micelle
      concentration (cmc) of the negatively charged monoRL is dependent on the ionic
      strength, whereas that of the protonated form is not, whereas the charge of the
      polar head of monoRL has little effect on the surface area. Dynamic light
      scattering showed that in the vicinity of the cmc structures with an average
      diameter of 50 nm are present, whereas at concentrations well above the cmc the
      size increases to about 200 nm. Taken together our results show that monoRL
      presents a monomer-to-micelle transition, which depends on pH and ionic strength,
      similar to that described before for the diRL species. However the formation of
      lamellar vesicles described for diRL at pH 7.4, was not observed here. Molecular
      dynamics (MD) simulations yielded a similar value for the lateral diffusion
      coefficient of protonated anionic monoRL, indicating that the negative charge
      does not affect biosurfactant mobility in the monolayer surface. The radial
      distribution function value is slightly higher for the protonated monoRL;
      therefore the number of molecules located at a particular distance is somehow
      higher in the case of the protonated form. On the other hand, it is clearly
      obtained that the carboxylate group of the anionic form moves more inside the
      aqueous phase as compared to the carboxyl group of the protonated form. The
      results obtained correspond to the expected behaviour for a biosurfactant
      molecule in relation to the dependence of protonation state and micelle
      formation, and therefore the molecular dynamics simulation appears to describe
      properly our molecular systems.

PMID- 23010029
TI  - Real-time analysis and direct observations of different superoxide dismutase
      (SOD1) molecules bindings to aggregates in temporal evolution step.
AB  - The misfolding and intracellular aggregation of Cu-Zn superoxide dismutase (SOD1)
      is pathologically key feature of amyotrophic lateral sclerosis (ALS). Although
      details of the mechanisms continue to be unclear, there are key steps in the
      possible pathway to the development of ALS. This study focuses on interactions
      between different SOD1 molecules (A4V apo/holo, and WT apo/holo) and homogeneous
      aggregates in the temporal evolution step, and a determination of whether any of
      the SOD1 molecules are reactive to the aggregates with the extent of binding, as
      determined by surface plasmon resonance (SPR) measurements. Using a kinetic
      binding model, the association constant of A4V apo was found to be three times
      larger than that for the WT apo species. Differences in the extent of the
      interactions were also simultaneously measured and visualized by means of SPR
      imaging techniques. The SPR-based approach suggests direct correlation between
      SPR signal and the extent of molecular binding, which can identify the
      significant contributors to the formation of macroaggregates of SOD1 in the
      temporal evolution step.

PMID- 23010030
TI  - The effect of various concentrations of papain on the properties and hydrolytic
      rates of beta-casein layers.
AB  - Recently, much attention has been focused on the investigation of the surface
      biocatalysis of proteases. In this study, papain, a proteolytic enzyme was used
      to hydrolyze a bovine beta-casein (beta-CN) layer, which was monitored by a
      quartz crystal microbalance with dissipation (QCM-D). The changes of the beta-CN
      layers before and after hydrolysis were characterized by atomic force microscopy
      (AFM) imaging, grazing angle infrared spectroscopy (GA-FTIR) spectra, and contact
      angle measurement. Our results demonstrated that the proteolytic reaction was
      enzyme concentration-dependent and started with the hydrophobic C-terminal
      sequence of the beta-CN. The remaining beta-CN layer became thinner, smoother,
      stiffer, and hydrophilic after hydrolysis. These results are conducive to the
      further understanding of the catalysis of papain on beta-CN layers in liquid
      solid interfaces and the promotion of biocatalytic applications.

PMID- 23010031
TI  - A novel approach for efficient immobilization and stabilization of papain on
      magnetic gold nanocomposites.
AB  - In the present study, a facile functionalization of magnetic nanoparticles has
      been described for the immobilization of enzyme that offers many advantages for
      reuse and excellent efficiencies. The magnetic gold nanocomposites have been
      fabricated for the successful immobilization of an industrially important enzyme
      "papain". For immobilization of papain on magnetic gold nanocomposites, magnetic
      nanoparticles were modified with 3-(mercaptopropyl) trimethoxy silane (MPTS).
      Further, the citrate stabilized gold nanoparticles were chemisorbed on these
      thiol coated magnetic nanoparticles to fabricate the desired magnetic gold
      nanocomposites. Papain containing net positive charge (isoelectric point of
      papain=8.75) in PBS buffer (pH 7.4) has immobilized on the surface of the
      negatively charged magnetic gold nanocomposites through the ionic or
      electrostatic interaction. The Michaelis-Menten kinetic constant (K(m)) and
      maximum reaction velocity (V(max)) for free papain were 0.236*10(5) g ml(-1) and
      4.08 g ml(-1)/s respectively whereas for immobilized papain, K(m) and V(max)
      values were 0.308*10(5) g ml(-1) and 5.4 g ml(-1)/s respectively. The loading
      amount of papain on magnetic gold nanocomposites was 54 mg/g support and the
      activity recovery of the immobilized papain reached to 47 (+/-5)% compared to
      native papain. The main advantage of this papain nanobiocatalyst is the easy
      isolation of enzyme from the reaction medium.

PMID- 23010033
TI  - Poly(L-aspartic acid) nanogels for lysosome-selective antitumor drug delivery.
AB  - Advanced materials that have controllable pH-responsive properties when submerged
      in the lysosome have a great potential in intracellular drug delivery. We
      developed novel poly(L-amino acid) nanogels that were prepared by a facile cross
      linking of poly[L-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol)
      maleimide [poly(L-Asp-g-DEAP)-b-PEG-Mal] and poly(L-aspartic acid-g-ethyl thiol)
      b-PEG [poly(L-Asp-SH)-b-PEG] in an oil/water emulsion condition. Interestingly,
      these nanogels (~125 nm in diameter) modulated volume expansion (~375 nm in
      diameter) in a lysosomal pH (~pH 5.0) due to an extensive proton absorption of
      DEAP at a low pH, which mediated lysosome swelling and the subsequent lysosome
      destabilization. In the in vitro tumor cell cytotoxicity test, they encouraged
      tumor cell death, probably owing to the leakage of lysosomal enzymes.
      Furthermore, encapsulating antitumor drug (e.g., doxorubicin, DOX) into these
      nanogels enhanced tumor cell cytotoxicity. We conclude that this nanogel system
      will have great potential for tumor therapy.

PMID- 23010032
TI  - Formation and retention of staphylococcal biofilms on DLC and its hybrids
      compared to metals used as biomaterials.
AB  - Staphylococcus epidermidis and Staphylococcus aureus cause most of the implant
      related infections. Antibiotic treatment often fails and cure requires surgical
      intervention. It was hypothesized that biomaterial coatings resistant to biofilms
      offer a preventive option. Physical vapour deposited diamond-like carbon (DLC)
      and its polytetrafluoroethylene (DLC-PTFE-h) and polydimethylsiloxane (DLC-PDMS
      h) hybrids were compared to titanium (Ti), tantalum (Ta) and chromium (Cr) thin
      films on silicon wafers for their resistance against formation and/or retention
      of biofilms produced by S. epidermidis and S. aureus in vitro. Sample surfaces
      were characterized for surface topography, contact angle and zeta-potential,
      because such properties might affect the biofilm. Biofilm was stained using
      calcofluor white and analysed in fluorescence microscopy using morphometry.
      Sixteen hour incubation was selected in pilot tests; at this checkpoint Ti, Ta,
      Cr and DLC-PDMS-h were almost fully covered by biofilm, but DLC and DLC-PTFE-h
      were only partially biofilm coated by S. epidermidis (88+/-26%, p<0.001 and 56+/
      39%, p<0.001, respectively) or S. aureus (81+/-24%, p<0.001 and 51+/-26%,
      p<0.001, respectively). DLC and its PTFE hybrid offer a potential biofilm hostile
      surface coating for implants and medical devices. This ability to resist biofilm
      formation and attachment could not be explained by only one factor, but it seems
      to be related to a combination of various properties, with electrokinetic
      streaming potential and protein coating being particularly important for its
      outcome.

PMID- 23010034
TI  - Chemical modification of a plant origin biomass using cationic surfactant ABDAC
      and the biosorptive decolorization of RR45 containing solutions.
AB  - This study focused on the improvement of the decolorization potential of biomass
      derived from Pyracantha coccinea. Alkyl benyzldimethyl ammonium chloride (ABDAC)
      was used as modification agent. Batch mode decolorization potential of modified
      biosorbent was explored at different operating conditions. ABDAC modification
      significantly increased the biosorption yield to 97.27%, which was 3.88 times
      higher than that of natural biomass. The prepared biosorbent was effectively used
      for the decolorization of Reactive Red 45 contaminated solutions after the
      optimization of biosorption conditions. The non-linear regression analysis was
      used to evaluate the isotherm and kinetic model parameters. Process followed the
      Langmuir isotherm model and the highest monolayer capacity of 152.49 mg g(-1) was
      obtained with a small amount of modified biosorbent. Kinetic studies indicated
      fast decolorization rate of the process following the pseudo-first-order model.
      Biosorption performance of the prepared biosorbent was tested in RR45 containing
      real wastewater sample. The possible dye biosorbent interactions in the
      biosorption process were explored by zeta potential, scanning electron microscobe
      and FTIR analysis.

PMID- 23010035
TI  - Physicochemical characterization of tensio-active produced by Geobacillus
      stearothermophilus isolated from petroleum-contaminated soil.
AB  - Biosurfactants are surface-active agents of microbial origin, and have a property
      of lowering the interfacial tension between two liquids. They act on the
      interface and are amphiphathic molecules; in with both hydrophilic and
      hydrophobic portions are present in the same molecule. However, the economics of
      producing biosurfactant has limited its commercial applications, and the costs
      can be reduced using cheap substrates or industrial waste. The present study
      showed the biosurfactant production using corn steep liquor and palm oil as
      carbon and nitrogen sources for reduction the costs of production. The
      biosurfactant production by Geobacillus stearothermophilus UCP 986 was carried
      out using optimized culture medium constituted by palm oil (7.5%) and corn steep
      liquor (4.5%) using Bioflo fermentor, at temperature of 45 degrees C, during 32 h
      and agitation of 300 rpm. The biosurfactant showed a reduction of the water
      surface tension of 72-31 mN/m and interfacial tension of 0.3 mN/m. The
      biosurfactant was obtained from the net metabolic liquid by acetone precipitation
      corresponding to the yield of 2.3g/L. The isolate biosurfactant showed a CMC of
      2.5% and non-ionic profile. The best emulsification index (E(24)) obtained was
      87% using motor oil burned. The biosurfactant solution (2.5%) used in oil
      spreading test increases the viscosity of engine burning oil of 149.2% and 138.2%
      to vegetable fat post-frying, respectively. The gas chromatography-mass
      spectrometer indicated at 29.52 min a molecular weight of 207 Da and eight peaks
      by FT-IR identified the chemical structure of the biosurfactant produced by G.
      stearothermophilus.

PMID- 23010036
TI  - Synthesis and anticoagulation activities of polymer/functional graphene oxide
      nanocomposites via Reverse Atom Transfer Radical Polymerization (RATRP).
AB  - The anticoagulation properties of biomaterials are crucial for biomedical
      applications, especially for blood-contacting materials. In this work, a range of
      functional graphene oxide based on the biomimetic monomer 2-(methacryloyloxy)
      ethyl phosphorylcholine (GO-g-pMPC) were synthesized by RATRP in alcoholic media
      using peroxide groups as initiator, and then filled into the polyurethane matrix
      to obtain the polyurethane (PU)/functional graphene oxide nanocomposite films
      (PU/GO-g-pMPC). The tensile strength and elongation and morphology of the PU/GO-g
      pMPC were characterized by mechanical properties test, Transmission electron
      microscope (TEM), respectively. The results showed that a small amount of
      graphene oxide can improve the mechanical properties of PU. The blood
      compatibility of the PU substrates was evaluated by protein adsorption tests and
      platelet adhesion tests in vitro. It was found that all the PU/GO-g-pMPC showed
      improved resistance to nonspecific protein adsorption and platelet adhesion.

PMID- 23010037
TI  - Biosynthesized silver nanoparticles by ethanolic extracts of Phytolacca decandra,
      Gelsemium sempervirens, Hydrastis canadensis and Thuja occidentalis induce
      differential cytotoxicity through G2/M arrest in A375 cells.
AB  - The capability of crude ethanolic extracts of certain medicinal plants like
      Phytolacca decandra, Gelsemium sempervirens, Hydrastis canadensis and Thuja
      occidentalis used as homeopathic mother tinctures in precipitating silver
      nanoparticles from aqueous solution of silver nitrate has been explored.
      Nanoparticles thus precipitated were characterized by spectroscopic, dynamic
      light scattering, X-ray diffraction, atomic force and transmission electron
      microscopic analyses. The drug-DNA interactions of silver nanoparticles were
      analyzed from data of circular dichroism spectroscopy and melting temperature
      profiles using calf thymus DNA (CT-DNA) as target. Biological activities of
      silver nanoparticles of different origin were then tested to evaluate their
      effective anti-proliferative and anti-bacterial properties, if any, by exposing
      them to A375 skin melanoma cells and to Escherichia coli C, respectively. Silver
      nanoparticles showed differences in their level of anti-cancer and anti-bacterial
      potentials. The nanoparticles of different origin interacted differently with CT
      DNA, showing differences in their binding capacities. Particle size differences
      of the nanoparticles could be attributed for causing differences in their
      cellular entry and biological action. The ethanolic extracts of these plants had
      not been tested earlier for their possible efficacies in synthesizing
      nanoparticles from silver nitrate solution that had beneficial biological action,
      opening up a possibility of having therapeutic values in the management of
      diseases including cancer.

PMID- 23010038
TI  - Biodeterioration of funeral sculptures in La Recoleta Cemetery, Buenos Aires,
      Argentina: pre- and post-intervention studies.
AB  - Stone materials exposed to weathering are subject to biological colonization and
      consequently to biofilm formation, causing biodeterioration. The color changes on
      the stone substrates caused by biogenic pigments, mechanical stress on the
      mineral structure due to extracellular polymeric substances (EPS) and the
      accumulation of atmospheric pollutants by the biofilm are some of the
      deteriogenic effects, which modify esthetic and functional aspects of the work.
      The aim of this study was to determine biodeterioration and biofilm formation on
      marble tombstones from La Recoleta Cemetery, Buenos Aires, Argentina. The effect
      of the biocide benzalkonium chloride on biofilm formation was studied, and a
      chart produced of the treated tombstones. Pre- and post-intervention
      microbiological studies, scanning electron microscopy and X-ray dispersion
      analysis showed a significant decrease of the biofilm flora after treatment.
      However, algae of the genus Trentepohlia were difficult to eradicate. These
      studies are a valuable contribution to determine restoration criteria against
      biofilm formation, to characterize chromatic variations of biological origin on
      the stone and to formulate conservation and restoration policies.

PMID- 23010039
TI  - Influence of TiN coating on the biocompatibility of medical NiTi alloy.
AB  - The biocompatibility of TiN coated nickel-titanium shape memory alloy (NiTi-SMA)
      was evaluated to compare with that of the uncoated NiTi-SMA. Based on the
      orthodontic clinical application, the surface properties and biocompatibility
      were characterized by scanning electron microscopy (SEM), X-ray diffraction
      (XRD), wettability test, mechanical test and in vitro tests including MTT, cell
      apoptosis and cell adhesion tests. It was observed that the bonding between the
      substrate and TiN coating is excellent. The roughness and wettability increased
      as for the TiN coating compared with the uncoated NiTi-SMA. MTT test showed no
      significant difference between the coated and uncoated NiTi-SMA, however the
      percentage of early cell apoptosis was significantly higher as for the uncoated
      NiTi alloy. SEM results showed that TiN coating could enhance the cell
      attachment, spreading and proliferation on NiTi-SMA. The results indicated that
      TiN coating bonded with the substrate well and could lead to a better
      biocompatibility.

PMID- 23010040
TI  - Adsorption of various antimicrobial agents to endotoxin removal polymyxin-B
      immobilized fiber (Toraymyxin(r)). Part 2: Adsorption of two drugs to Toraymyxin
      PMX-20R cartridges.
AB  - In our previous study, the degree of adsorption of 9 representative antimicrobial
      agents to Toraymyxin((r)) PMX-F sheets was quantitatively evaluated. As a result,
      the adsorption rate was 22.1% for Linezolid in the presence of serum. Therefore,
      we investigated whether two types of antimicrobial agents (Ciprofroxacin and
      Linezolid) can be better adsorbed on PMX-F sheets. When the number of PMX-F
      sheets was increased in a step wise manner, specifically 2, 4, 6, 8 and 12, the
      adsorption rate increased linearly. In addition, the adsorption to polymyxin-B
      immobilized fiber (Toraymyxin((r)) PMX-20R) cartridges, widely used to remove
      endotoxins from circulating blood in the treatment of sepsis, was quantitatively
      evaluated. As a result, in the presence of serum, Linezolid showed adsorption to
      PMX-20R, and the adsorption rate after 2h was 54.5%, and that after 4h was 65.8%.
      The results of this study suggest the necessity of monitoring blood antimicrobial
      concentration during treatment for sepsis with Linezolid, which showed adsorption
      to PMX-20R in an environment close to a clinical environment.

PMID- 23010041
TI  - Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after
      oral administration in rats.
AB  - The aim of this study was to assess the potential of nanoparticles to improve the
      pharmacokinetics of curcumin, with a primary goal of enhancing its
      bioavailability. Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol
      (PEG) (PLGA-PEG) blend nanoparticles containing curcumin were obtained by a
      single-emulsion solvent-evaporation technique, resulting in particles size
      smaller than 200 nm. The encapsulation efficiency was over 70% for both
      formulations. The in vitro release study showed that curcumin was released more
      slowly from the PLGA nanoparticles than from the PLGA-PEG nanoparticles. A LC
      MS/MS method was developed and validated to quantify curcumin in rat plasma. The
      nanoparticles were orally administered at a single dose in rats, and the
      pharmacokinetic parameters were evaluated and compared with the curcumin aqueous
      suspension. It was observed that both nanoparticles formulations were able to
      sustain the curcumin delivery over time, but greater efficiency was obtained with
      the PLGA-PEG nanoparticles, which showed better results in all of the
      pharmacokinetic parameters analyzed. The PLGA and PLGA-PEG nanoparticles
      increased the curcumin mean half-life in approximately 4 and 6h, respectively,
      and the C(max) of curcumin increased 2.9- and 7.4-fold, respectively. The
      distribution and metabolism of curcumin decreased when it was carried by
      nanoparticles, particularly PLGA-PEG nanoparticles. The bioavailability of
      curcumin-loaded PLGA-PEG nanoparticles was 3.5-fold greater than the curcumin
      from PLGA nanoparticles. Compared to the curcumin aqueous suspension, the PLGA
      and PLGA-PEG nanoparticles increased the curcumin bioavailability by 15.6- and
      55.4-fold, respectively. These results suggest that PLGA and, in particular, PLGA
      PEG blend nanoparticles are potential carriers for the oral delivery of curcumin.

PMID- 23010042
TI  - Poly(epsilon-caprolactone) modified with fusion protein containing self-assembled
      hydrophobin and functional peptide for selective capture of human blood outgrowth
      endothelial cells.
AB  - Human blood outgrowth endothelial cells (HBOECs)-specific binding peptide,
      TPSLEQRTVYAK (TPS), was proposed to be applied on autologous cell therapy for
      treating cardiovascular diseases. Hydrophobins, as a family of self-assembly
      proteins originated from fungi, have demonstrated unique characteristics to
      modulate surface properties of other materials coated with these amphiphilic
      proteins in previous studies. In this report, a fusion protein which was composed
      of class I hydrophobin HGFI originated from Grifola frondosa and functional
      peptide TPS was expressed by Pichia pastoris expression system. Then, we purified
      this fusion protein by ultrafiltration and reverse-phase high performance liquid
      chromatography. Water contact angle, X-ray photoelectron spectroscopy
      measurements indicated that the surface properties of hydrophobin were greatly
      preserved by this fusion protein while comparing with wild HGFI. Cell binding
      assay showed that this fusion protein demonstrated specific binding property to
      HBOECs while coating on biodegradable poly(epsilon-caprolactone) (PCL) grafts in
      the presence of fetal bovine serum, whereas HGFI-coated PCL non-selectively
      enhanced all types of cells attachments. Methylthiazol tetrazolium assay was
      employed to verify the cytocompatibility of this fusion protein-based material.
      This work presented a new perspective to apply hydrophobin in tissue engineering
      and regenerative medicine and provided an alternative approach to study
      endothelial progenitor cells.

PMID- 23010043
TI  - Improving the binding capacity of Ni2+ decorated porous magnetic silica spheres
      for histidine-rich protein separation.
AB  - Biomagnetic immobilization of histidine-rich proteins based on the single-step
      affinity adsorption of transition metal ions continues to be a suitable practice
      as a cost effective and a up scaled alternative to the to multiple-step
      chromatographic separations. In our previous work, we synthesised Porous Magnetic
      silica (PMS) spheres by one-step hydrothermal-assisted modified-stober method.
      The obtained spheres were decorated with Ni(2+) and Co(2+), and evaluated for the
      capture of a H6-Tagged green fluorescence protein (GFP-H6) protein. The binding
      capacity of the obtained spheres was found to be slightly higher in the case
      Ni(2+) decorated PMS spheres (PMSNi). However, comparing with commercial
      products, the binding capacity was found to be lower than the expected. In this
      way, the present work is an attempt to improve the binding capacity of PMSNi to
      histidine-rich proteins. We find that increasing the amount of Ni(2+) onto the
      surface of the PMS spheres leads to an increment of the binding capacity to GFP
      H6 by a factor of two. On the other hand, we explore how the size of histidine
      rich protein can affect the binding capacity comparing the results of the GFP-6H
      to those of the His-tagged alpha-galactosidase (alpha-GLA). Finally, we
      demonstrate that the optimization of the magnetophoresis parameters during
      washing and eluting steps can lead to an additional improvement of the binding
      capacity.

PMID- 23010044
TI  - Solvent and concentration effects on the surface characteristics and platelet
      compatibility of zwitterionic sulfobetaine-terminated self-assembled monolayers.
AB  - The structural organization of a monolayer influences biological responses as the
      material makes contact with the bodily fluid. Zwitterionic materials containing
      the sulfobetaine functionalities have been shown to exhibit protein-repelling
      characteristics. In this study, the effect of solvent and thiol concentrations on
      the sulfobetaine-terminated SAM (self-assembled monolayer) is discussed. Four
      different types of solvents were selected: deionized water, PBS, methanol and
      ethanol. The total thiol concentration was set at either 2mM or 0.1 mM. X-ray
      photoelectron analyses indicated that all SAMs demonstrated similar chemical
      configurations. Reflection adsorption infrared spectroscopy showed that
      conformation of the SAMs was more organized when prepared from a 0.1 mM solution
      compared to a 2 mM solution. The contact angle of the SAMs prepared from 2 mM
      concentration was dependent upon the solvent utilized and was more hydrophobic
      than the SAMs prepared from 0.1 mM concentration. Moreover, all of these
      sulfobetaine-terminated SAMs showed a fairly negative zeta potential in PBS at pH
      7.4. After contact with blood, these sulfobetaine-terminated SAMs demonstrated
      distinct platelet reactivity among each other. The highest platelet compatibility
      was shown on the SAMs prepared in 0.1 mM solution and the one formed in 2 mM
      ethanolic solution, where they exhibited a more organized conformation and
      enhanced hydrophilic properties. These properties might be caused by the
      different hydration layers, which are affected by the assembly conditions on the
      topmost monolayer. This study demonstrated that optimizing solvent and
      concentration conditions could control the structural organization of
      zwitterionic sulfobetaine-terminated SAMs and, consequently, modify biomedical
      properties.

PMID- 23010045
TI  - Synthesis of latex-antigen complexes from single and multiepitope recombinant
      proteins. Application in immunoagglutination assays for the diagnosis of
      Trypanosoma cruzi infection.
AB  - The physical adsorption and the chemical coupling of recombinant proteins of
      Trypanosoma cruzi onto polystyrene and core-shell carboxylated particles were
      respectively investigated with the ultimate aim of producing latex-protein
      complexes to be used in an immunoagglutination assay able to detect the Chagas
      disease. To this effect, two single proteins (RP1 and RP5) and a multiepitope
      protein derived from three antigenic peptides (CP2) were evaluated, and
      sensitizations were carried out at different pHs. The maximum physical adsorption
      was produced at pHs close to the protein isoelectric point (i.e., pH 6 for RP5
      and pH 5 for RP1 and CP2). High fractions of antigens were chemically bound to
      the carboxyl groups, and the highest surface density of linked protein was also
      observed at pHs close to the protein isoelectric point. The three latex-protein
      complexes obtained by covalent coupling at such pHs were tested with sera from a
      panel of 16 infected and 16 non-infected patients. In the immunoagglutination
      assays, the latex-CP2 complex produced the best discrimination between positive
      and negative sera.

PMID- 23010046
TI  - Partition in aqueous two-phase system: its application in downstream processing
      of tannase from Aspergillus niger.
AB  - Tannase from Aspergillus niger was partitioned in aqueous two-phase systems
      composed by polyethyleneglycol of molar mass 400, 600 and 1000 and potassium
      phosphate. Tannase was found to be partitioned toward the salt-rich phase in all
      systems, with partition coefficients lower than 0.5. Partition coefficients
      values and low entropic and enthalpic changes associated with tannase partition
      suggest that the entropic effect may be the driving force of the concentration of
      the enzyme in the bottom phase due to the high molar mass of the enzyme. The
      process was significantly influenced by the top phase/bottom phase volume ratio.
      When the fungal culture broth was partitioned in these systems, a good
      performance was found, since the enzyme recovery in the bottom phase of the
      system composed by polyethyleneglycol 1000 was around 96% with a 7.0-fold
      increase in purity.

PMID- 23010047
TI  - Interactions between ionic liquid surfactant [C12mim]Br and DNA in dilute brine.
AB  - Interactions between ionic liquid surfactant [C(12)mim]Br and DNA in dilute brine
      were investigated in terms of various experimental methods and molecular dynamics
      (MD) simulation. It was shown that the aggregation of [C(12)mim]Br on DNA chains
      is motivated not only by electrostatic attractions between DNA phosphate groups
      and [C(12)mim]Br headgroups but also by hydrophobic interactions among
      [C(12)mim]Br alkyl chains. Isothermal titration calorimetry analysis indicated
      that the [C(12)mim]Br aggregation in the presence and absence of DNA are both
      thermodynamically favored driven by enthalpy and entropy. DNA undergoes size
      transition and conformational change induced by [C(12)mim]Br, and the charges of
      DNA are neutralized by the added [C(12)mim]Br. Various microstructures were
      observed such as DNA with loose coil conformation in nature state, necklace-like
      structures, and compact spherical aggregates. MD simulation showed that the
      polyelectrolyte collapses upon the addition of oppositely charged surfactants and
      the aggregation of surfactants around the polyelectrolyte was reaffirmed. The
      simulation predicted the gradual neutralization of the negatively charged
      polyelectrolyte by the surfactant, consistent with the experimental results.

PMID- 23010048
TI  - Design of pH-responsive nanoparticles of terpolymer of poly(methacrylic acid),
      polysorbate 80 and starch for delivery of doxorubicin.
AB  - This work focused on the design of new pH-responsive nanoparticles for controlled
      delivery of anticancer drug doxorubicin (Dox). Nanoparticles of poly(methacrylic
      acid)-polysorbate 80-grafted starch (PMAA-PS 80-g-St) were synthesized by using a
      one-pot method that enabled simultaneous grafting of PMAA and PS 80 onto starch
      and nanoparticle formation in an aqueous medium. The particles were characterized
      by FTIR, (1)H NMR, TEM, DLS, and potentiometric titration. Dox loading and in
      vitro release from the nanoparticles were investigated. The FTIR and (1)H NMR
      confirmed the chemical composition of the graft terpolymer. The nanoparticles
      were relatively spherical with narrow size distribution and porous morphology.
      They exhibited pH-dependent swelling in a physiological pH range. The particle
      size and magnitude of phase transition were dependent on polymer composition and
      formulation parameters such as concentrations of surfactant and cross-linking
      agent and total monomer concentration. The nanoparticles with optimized
      compositions showed high loading capacity for Dox and sustained Dox release. The
      results suggest that the new pH-responsive terpolymer nanoparticles are useful in
      controlled drug delivery.

PMID- 23010049
TI  - Development of solid self-nanoemulsifying granules (SSNEGs) of ondansetron
      hydrochloride with enhanced bioavailability potential.
AB  - The current work aims to prepare the solid self-nanoemulsifying granules (SSNEGs)
      of ondansetron hydrochloride (ONH) to enhance its oral bioavailability by
      improving its aqueous solubility and facilitating its absorption though lymphatic
      pathways. Preformulation studies including screening of excipients for solubility
      and pseudoternary phase diagrams suggested the suitability of Capmul MCM as
      lipid, Labrasol as surfactant, and Tween 20 as cosurfactant for preparation of
      self-emulsifying formulations. Preliminary composition of the SNEDDS formulations
      were selected from the phase diagrams and subjected to thermodynamic stability
      studies and dispersibility tests. The prepared liquid SNEDDS formulations were
      characterized for viscosity, refractive index, droplet size and zeta potential.
      The TEM study confirmed the formation of nanoemulsion following dilution of
      liquid SNEDDS. The optimized liquid SNEDDS were transformed into free flowing
      granules by adsorption on the porous carriers like Sylysia (350, 550, and 730)
      and NeusilinTM US2. Solid state characterization employing the FTIR, DSC and
      powder XRD studies indicated lack of any significant interaction of drug with the
      lipidic and emulsifying excipients, and porous carriers. In vitro drug release
      studies indicated faster solubilization of the drug by optimized SSNEGs (over 80%
      within 30 min) vis-a-vis the pure drug (only 35% within 30 min). In vivo
      pharmacokinetic studies in Wistar rats observed significant increase in C(max)
      (3.01-fold) and AUC (5.34-fold) using SSNEGs compared to pure drug, whereas no
      significant difference (p>0.1) was observed with the liquid SNEDDS. Thus, the
      present studies ratify the bioavailability enhancement potential of SSNEGs of ONH
      prepared using porous carriers.

PMID- 23010050
TI  - TiO2 nanorods via one-step electrospinning technique: a novel nanomatrix for
      mouse myoblasts adhesion and propagation.
AB  - This study was aimed at the synthesis and characterization of novel Titania
      nanorods by sol-gel electrospinning technique. The physicochemical properties of
      the synthesized nanorods were determined by field emission scanning electron
      microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), transmission
      electron microscopy (TEM), and X-ray diffraction (XRD) pattern. To examine the in
      vitro cytotoxicity, mouse myoblast C2C12 cells were treated with different
      concentrations of as prepared TiO(2) nanorods and the viability of cells was
      analyzed by Cell Counting Kit-8 assay at regular time intervals. The
      morphological features of the cells attached with nanorods were examined by Bio
      SEM. Cytotoxicity experiments indicated that the mouse myoblast cells could
      attach to the TiO(2) nanorods after being cultured. We observed that TiO(2)
      nanorods could support cell adhesion and growth and guide spreading behavior of
      myoblasts. We conclude that the electrospun TiO(2) nanorods scaffolds with unique
      morphology had excellent biocompatibility. Thus, the current work demonstrates
      that the as-synthesized TiO(2) nanorods represent a promising biomaterial to be
      exploited for various tissue engineering applications.

PMID- 23010051
TI  - Synthesis and evaluation of antioxidant and antibacterial behavior of CuO
      nanoparticles.
AB  - CuO nanoparticles were synthesized by thermal decomposition methods and
      characterized by UV-visible spectroscopy, XRD and TEM analysis. The resultant
      particles are nearly spherical and particle size is in the range of 15-30 nm. The
      antioxidant behavior of synthesized CuO nanoparticles was evaluated by scavenging
      free radicals of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH). The free radical
      scavenging activity of CuO nanoparticles was monitored by UV-visible
      spectrophotometry. The antibacterial activity of CuO nanoparticles was tested
      against different bacterial strains. CuO nanoparticles showed efficient
      antioxidant activity and bactericidal effect against Eschericia coli and
      Pseudomonas aeruginosa.

PMID- 23010052
TI  - Formulation of Tyloxapol niosomes for encapsulation, stabilization and
      dissolution of anti-tubercular drugs.
AB  - The present study delineates the formulation of niosomes from biocompatible
      surfactant Tyloxapol and their potential as drug delivery system for anti
      tuberculosis drugs. Drug loaded niosomes have a size of 150 nm with a loading
      efficiency of 97.95+/-0.2, 98.89+/-0.2 and 99.50+/-0.2% for rifampicin (RIF),
      isoniazid (INH), pyrazinamide (PZA), respectively. Fourier transform infrared
      spectroscopic studies infer that the drugs are in harmony with the fabricated
      niosomes since no visible interactions between the drug and niosomes have been
      detected. The prepared formulations are quite stable as assessed using absorption
      spectroscopy. TEM images and photoluminescence results reveal that RIF and INH
      are located in the film bilayer whereas PZA is adsorbed mainly on the surface
      head groups. In vitro dissolution studies at physiological conditions have been
      undertaken to compare the release behavior of drugs from the prepared niosomes.
      Sustained release has been achieved for hydrophilic drugs and an acceptable
      release in case of RIF. Comparison of regression coefficients of different
      kinetic models reveal that INH release follows Fickian diffusion mechanism
      whereas RIF and PZA, a non-Fickian release mechanism. Such a versatile system is
      expected to reduce dose-related drug toxicity and reach the atelectatic areas.

PMID- 23010053
TI  - Mechanism of HSA adsorption on mica determined by streaming potential, AFM and
      XPS measurements.
AB  - Adsorption of human serum albumin (HSA) on mica at pH 3.5 (0.15M NaCl) was
      studied using in situ streaming potential measurements, AFM imaging and XPS.
      Results obtained by streaming potential were consistent with AFM measurements and
      theoretical predictions based on the random sequential adsorption model. These
      results in combination with complementary data derived from XPS allowed one to
      determine both the kinetics of adsorption and the maximum coverage of
      irreversibly bound HSA, which was close to 1.6 mg m(-2) (dimensionless coverage
      0.45). It was concluded that HSA adsorption on mica at pH 3.5 occurred under side
      on, electrostatically controlled mechanisms with no tendency to multilayer
      formation. Such irreversible bound HSA monolayers of well-defined coverage can
      find applications for performing efficient immunological tests, designing
      biomaterials surfaces and biosensors.

PMID- 23010054
TI  - Facile synthesis of cysteine and triethanolamine capped CdTe nanoparticles.
AB  - Cysteine and triethanolamine capped CdTe nanoparticles have been synthesized
      using a simple aqueous solution based method. This method involves the reaction
      of tellurium powder with sodium borohydride (NaBH(4)) in water to produce
      telluride ions (Te(2-)), followed by the simultaneous addition of an aqueous
      solution of cadmium chloride or other cadmium source (acetate, carbonate and
      nitrate) and solution of L-cysteine ethyl ester hydrochloride or triethanolamine.
      The effect of capping agent on the size, structure and morphology of the as
      synthesized nanoparticles was investigated. The particles were characterized
      using optical spectroscopy, transmission electron microscopy (TEM), high
      resolution TEM (HRTEM), X-ray diffraction (XRD) and Fourier transform infrared
      (FT-IR) spectroscopy.

PMID- 23010055
TI  - Novel durable bio-photocatalyst purifiers, a non-heterogeneous mechanism:
      accelerated entrapped dye degradation into structural polysiloxane-shield nano
      reactors.
AB  - This research has designed innovative Ag/TiO(2) polysiloxane-shield nano-reactors
      on the PET fabric to develop novel durable bio-photocatalyst purifiers. To create
      these very fine nano-reactors, oppositely surface charged multiple size
      nanoparticles have been applied accompanied with a crosslinkable amino
      functionalized polysiloxane (XPs) emulsion. Investigation of photocatalytic dye
      decolorization efficiency revealed a non-heterogeneous mechanism including an
      accelerated degradation of entrapped dye molecules into the structural
      polysiloxane-shield nano-reactors. In fact, dye molecules can be adsorbed by both
      Ag and XPs due to their electrostatic interactions and/or even via forming a
      complex with them especially with silver NPs. The absorbed dye and active oxygen
      species generated by TiO(2) were entrapped by polysiloxane shelter and the
      presence of silver nanoparticles further attract the negative oxygen species
      closer to the adsorbed dye molecules. In this way, the dye molecules are in close
      contact with concentrated active oxygen species into the created nano-reactors.
      This provides an accelerated degradation of dye molecules. This non-heterogeneous
      mechanism has been detected on the sample containing all of the three components.
      Increasing the concentration of Ag and XPs accelerated the second step beginning
      with an enhanced rate. Further, the treated samples also showed an excellent
      antibacterial activity.

PMID- 23010056
TI  - Optimized nanoemulsifying systems with enhanced bioavailability of carvedilol.
AB  - The current studies entail a novel approach of formulating the solid self
      nanoemulsifying drug delivery systems (S-SNEDDS) of carvedilol solely using
      rational blends of lipidic and emulsifying excipients without using equipment
      intensive techniques and/or inert porous carriers. Delineating the nanoemulsion
      regions, the amounts of Capmul MCM (i.e., lipid) and Nikkol HCO 50 (i.e.,
      emulgent) were selected as the critical factors for systematically formulating
      the optimized S-SNEDDS employing face centered cube design. The optimized
      formulation (mean globule size: 40.8 nm) indicated marked improvement in drug
      release profile vis-a-vis pure drug and marketed formulation. Augmentation in the
      values of C(max) (134.2%) and AUC (85.2%) indicated significant enhancement in
      the rate and extent of bioavailability by the S-SNEDDS formulation compared to
      pure drug. In situ SPIP studies ascribed the significant enhancement in
      absorptivity parameters of SNEDDS formulations to transport through the lymphatic
      system and reduced P-gp efflux. Successful establishment of various levels of in
      vitro/in vivo correlations (IVIVC's) substantiated the judicious choice of the in
      vitro dissolution milieu for simulating the in vivo conditions. The optimized
      formulation was found to be quite stable during six months of study period. The
      current investigations, therefore, report the successful development of
      systematically optimized S-SNEDDS with enhanced bioavailability potential of
      carvedilol.

PMID- 23010057
TI  - A novel lipid nanoemulsion system for improved permeation of granisetron.
AB  - A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed
      and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell
      monolayers. Particle size, polydispersity index (PI) and stability of the
      prepared GRN-loaded LNE systems were also characterized. The mean diameters of
      prepared LNEs were around 50 nm with PI<0.2. Developed LNEs were stable at 4
      degrees C in the dark place over a period of 12 weeks. In vitro drug dissolution
      and cytotoxicity studies of GRN-loaded LNEs were performed. GRN-loaded LNEs
      exhibited significantly higher drug dissolution than GRN suspension at pH 6.8 for
      2h (P<0.05). In vitro permeation study in Caco-2 cell monolayers showed that the
      LNEs significantly enhanced the drug permeation compared to GRN powder. The in
      vivo toxicity study in the rat jejunum revealed that the prepared GRN-loaded LNE
      was as safe as the commercial formulation (Kytril). These results suggest that
      LNE could be used as a potential oral liquid formulation of GRN for anti-emetic
      treatment on the post-operative and chemotherapeutic patients.

PMID- 23010058
TI  - A novel immunosensor for detecting toxoplasma gondii-specific IgM based on
      goldmag nanoparticles and graphene sheets.
AB  - A novel electrochemical immunosensor for detecting toxoplasma gondii-specific IgM
      (Tg-IgM) was constructed based on goldmag (Au-Fe(3)O(4)) nanoparticles and
      graphene sheets (GS). Thionine (Thi), as a mediator, was first electropolymerized
      on a nafion-GS (Nf-GS) modified electrode. Subsequently, gold nanoparticles
      (AuNPs) were attached onto the poly-thionine film through pi-stacking
      interactions, and then were used to immobilize toxoplasma gondii antigen (Tg-Ag)
      for immunosensor fabrication. A sandwich-type immunoassay for Tg-IgM was
      performed using Au-Fe(3)O(4) labeled anti-IgM-horseradish peroxidase (HRP) as
      trace label. Electrochemical detection was carried out in the presence of
      H(2)O(2) as HRP substrate. Using Au-Fe(3)O(4) provided a simple, non-chemical
      damaging method for regeneration, and enhanced the HRP reduction ability toward
      H(2)O(2). The AuNPs/Thi/Nf-GS nanocomposite also had good conductivity and
      biocompatibility, which effectively improved the immunosensor sensitivity. Under
      optimal conditions, the immunosensor can detect Tg-IgM in two linear ranges from
      0.0375 to 1.2 AU mL(-1) and from 2.0 to 18 AU mL(-1) with a detection limit of
      0.016 AU mL(-1) (S/N=3). The immunosensor exhibited good reproducibility,
      stability, and selectivity as well.

PMID- 23010059
TI  - Designing carboxymethyl cellulose based layer-by-layer capsules as a carrier for
      protein delivery.
AB  - Stable hollow microcapsules composed of sodium carboxymethyl cellulose (CMC) and
      poly (allylamine hydrochloride) (PAH) were produced by layer-by-layer adsorption
      of polyelectrolytes onto CaCO(3) microparticles. Subsequently the core was
      removed by addition of chelating agents for calcium ions. Zeta potential studies
      showed charge reversal with deposition of successive polyelectrolyte layers,
      indicating that the alternate electrostatic adsorption of polyelectrolytes of
      opposite charge was successfully achieved. The size and surface morphology of the
      capsules was characterized by various microscopy techniques. The pH responsive
      loading behavior was elucidated by confocal laser scanning microscopy (CLSM)
      studies using fluorescence labeled dextran (FITC-dextran) and labeled BSA (FITC
      BSA). CLSM images confirmed the open (pH<=6) and closed state (pH>=7) of the
      capsules. A model drug bovine serum albumin (BSA) was spontaneously loaded below
      its isoelectric point into hollow microcapsules, where BSA is positively charged.
      The loading of the BSA into the microcapsules was found to be dependent on the
      feeding concentration and pH of the medium. 65% of the loaded BSA was released
      over 7h of which about 34% was released in the first hour. These findings
      demonstrate that (CMC/PAH)(2) hollow capsules can be further exploited as a
      potential drug delivery system.

PMID- 23010060
TI  - A nano complex of hydrophilic phthalocyanine and polyethylenimine for improved
      cellular internalization efficiency and phototoxicity.
AB  - To enhance the cellular internalization and phototoxicity of sulfonated aluminum
      phthalocyanine (AlPcS), a hydrophilic photosensitizer (PS), nano complexes
      composed of a mixture of AlPcS (negatively charged) and polyethylenimine (PEI;
      positively charged) with different weight ratios of PEI to AlPcS were prepared
      via electrostatic interaction. The size of the PEI/AlPcS 0.6 (weight
      ratio=PEI/AlPcS) was below 200 nm with a monodispersed size distribution. The
      cellular uptake of the complex was determined using a fluorescence image test, a
      cell lysis test and confocal observation. The cellular internalization of AlPcS
      in the PEI/AlPcS 0.6 nano complex was 87 times higher than that of free AlPcS
      after 6h. The photoactivity of the nano complex, as measured by fluorescence
      intensity and singlet oxygen generation activity in PBS buffer, was completely
      eliminated by a self-quenching effect. After cellular uptake, the loss of the
      fluorescence intensity was restored by the dissociation of the nano complex.
      Additionally, the phototoxicity of the complex, both with and without light
      irradiation, was investigated using an MTT colorimetric assay. Although the free
      AlPcS did not exhibit phototoxicity, the nano complex showed strong phototoxicity
      after irradiation. Therefore, we suggest that the nano complex system has
      potential use in clinical photodynamic therapy and in the biological study of
      various cancers.

PMID- 23010061
TI  - Rupture of single receptor-ligand bonds: a new insight into probability
      distribution function.
AB  - Single molecule force spectroscopy is widely used to determine kinetic parameters
      of dissociation by analyzing bond rupture data obtained via applying mechanical
      force to cells, capsules, and beads that are attached to an intermolecular bond.
      The current analysis assumes that the intermolecular bond force is equal to the
      externally applied mechanical force. We confirm that viscous drag alone or in
      combination with cellular deformation resulting in viscoelasticity modulates bond
      force so that the instantaneous intermolecular bond force is not equivalent to
      the applied force. The bond force modulation leads to bond rupture time and force
      histograms that differ from those predicted by probability distribution function
      (PDF) using the current approach. A new methodology that accounts for bond force
      modulation in obtaining PDF is presented. The predicted histograms from the new
      methodology are in excellent agreement with the respective histograms obtained
      from Monte Carlo simulation.

PMID- 23010062
TI  - [An unusual cause of hemoptysis: a leech].
AB  - We report an exceptional case of hemoptysis observed in a 71-year-old woman with
      an uneventful past history. After 48 hours of admission, the patient
      spontaneously expelled a leech from the nose. The parasite was examined in
      parasitology laboratory, which confirmed the hemiptera. The infestation of the
      airway by a leech is not uncommon; however, this diagnosis is rarely mentioned.
      The clinical symptoms are variable depending on location and the diagnosis should
      be made rapidly to prevent complications. Whatever the localization, removing the
      parasite is difficult. Evolution after treatment is rapidly favorable, with
      complete disappearance of symptoms.

PMID- 23010063
TI  - Discriminating Thatcherised from typical faces in a case of prosopagnosia.
AB  - We report data from a prosopagnosic patient (PHD), and aged-matched control
      participants, from experiments where participants categorised individually
      presented emotional faces (experiment 1) and Thatcherised (from typical) faces
      (experiment 2). In experiment 2 participants also discriminated between
      simultaneously presented Thatcherised and typical faces. PHD was at chance
      categorising Thatcherised from typical faces. He was, however, able to
      discriminate between Thatcherised and typical faces, and partially able to
      categorise emotional faces. The results are discussed in terms of a loss of
      configural processing but preserved feature processing in PHD. The loss of
      configural processing impacts his categorisation of Thatcherised and typical
      faces, and his emotion processing, while his preserved feature processing
      supports his ability to categorise some emotional faces and his ability to
      discriminate between Thatcherised and typical faces.

PMID- 23010064
TI  - Does bimanual grasping of the Muller-Lyer illusion provide evidence for a
      functional segregation of dorsal and ventral streams?
AB  - Studies claiming a differential processing of visual illusions for perception and
      action have been subjected to many challenges. One criticism is that attentional
      demands were mismatched between the perception and action tasks. Dewar and Carey
      (2006) reexamined this argument by comparing bimanual grasping to bimanual size
      estimation and concluded that manual size estimation (ManEst) was affected by the
      illusion to a greater extent than grasping, supporting the case for two
      functionally distinct streams of visual processing. We tested whether this result
      may be due to their use of closed loop visual conditions by replicating their
      study under both closed and open loop conditions. We found that the difference in
      illusion effects between grasping and ManEst disappeared under open loop
      conditions, indicating that Dewar and Carey's findings can be explained by the
      availability of visual feedback and not a perception/action dissociation. We also
      discuss potential shortcomings of bimanual designs.

PMID- 23010065
TI  - [The first cases of influenza A/HINI diagnosed in Spain].

PMID- 23010066
TI  - Gamma knife radiosurgery for symptomatic brainstem intra-axial cavernous
      malformations.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      gamma knife radiosurgery (GKRS) for the treatment of symptomatic brainstem intra
      axial cavernous malformations (CMs) associated with high surgical morbidity.
      METHODS: Twenty-one patients with symptomatic brainstem intra-axial CMs were
      treated by GKRS between 2005 and 2010. One patient was lost to follow-up. The
      median age of the patients was 39.5 years (range, 24-69 years). All patients had
      experienced 1 or more symptomatic hemorrhages before GKRS (range, 1-3). The
      median marginal radiation dose was 13 Gy, and the median volume of the
      malformation was 0.56 mL. The median follow-up period after radiosurgery was 32
      months (range, 12-82 months; mean, 38.9 months). RESULTS: Before GKRS, 31
      hemorrhages (1.55 per patient) were observed. The annual hemorrhage rate before
      GKRS was 39.5%, excluding the first hemorrhage. After GKRS, 1 hemorrhage (0.05
      per patient) was identified. It occurred 6 months after radiosurgery. The patient
      showed complete recovery to a premorbid status with steroid medication. The
      annual hemorrhage rate after GKRS was 8.2% for the first 2 years. After the
      expected latency period, no hemorrhages were identified. One patient (5%)
      exhibited permanent paresthesia, which was a new neurologic symptom in absence of
      any hemorrhagic event, after the radiosurgery. CONCLUSIONS: GKRS seems to be
      relatively effective and safe for reducing the rebleeding rate of brainstem intra
      axial CMs that have high surgical risk. Careful selection of a low marginal dose
      and an optimal radiosurgical technique are helpful to achieve good outcomes.

PMID- 23010067
TI  - Percutaneous access to the vertebral bodies: a video and fluoroscopic overview of
      access techniques for trans-, extra-, and infrapedicular approaches.
AB  - OBJECTIVE: With increasing popularity of percutaneous spinal access for minimally
      invasive spinal neurosurgery, the treatment paradigm has shifted from open
      approaches to vertebroplasty or kyphoplasty for degenerative spinal disease and
      vertebral compression fractures. Addressing the challenges of this shift, we
      integrate the fluoroscopic studies of these percutaneous approaches with the
      three-dimensional surgical anatomy. Step-by-step techniques are illustrated in
      video demonstrations that highlight the nuances of effective percutaneous access
      during spinal surgeries for vertebral compression fractures and pedicle screw
      fixation. METHODS: Imaging guidelines, approach planning, surgical techniques,
      and relevant anatomical features are noted for the transpedicular, lumbar
      extrapedicular, and thoracic extra- and infrapedicular approaches. Video clips
      and accompanying fluoroscopic images highlight the critical steps. Subtle
      refinements unique to each percutaneous access are presented related to skin
      incision, needle trajectory, and cement deposition. RESULTS: With the
      transpedicular approach (popular technique for vertebroplasty and pedicle screw
      placement), safe access requires accurate interpretation of the fluoroscopic
      anatomy, specifically identification of the target vertebral body in true
      anterior-posterior and lateral planes. The transpedicular trajectory uses the
      slight inferior and medial orientation of the pedicle followed anteriorly. The
      lumbar extrapedicular approach uses an oblique trajectory anterior to the
      transverse process at the level of the pedicles. A thoracic approach uses the
      potential space between the rib head, transverse process, and pedicle. The
      infrapedicular approach, which allows greater flexibility in its medial
      angulation but at the expense of the bony confines of the thoracic extrapedicular
      approach, takes advantage of the narrow-waisted thoracic laminae. CONCLUSIONS:
      With an appreciation for the standard anatomical landmarks, fluoroscopic views,
      and avenues of approach, percutaneous access techniques can be safely and
      effectively applied to many spinal procedures.

PMID- 23010068
TI  - Factors influencing the prognosis in intracranial dural arteriovenous fistulas
      with perimedullary drainage.
AB  - OBJECTIVE: Intracranial dural arteriovenous fistulas with perimedullary venous
      drainage (IDAVFPD) are classified as type V dural arteriovenous fistulas.
      Publications are limited to single case reports and small case series. We
      conducted a systematic review of the literature for patients with IDAVFPD. The
      aim of this study is to identify the predictive factors of poor prognosis in
      patients with IDAVFPD. METHODS: We present the case of a 48-year-old man who
      underwent surgical interruption of IDAVFPD. A complete MEDLINE search was then
      undertaken for all articles reporting outcomes data for IDAVFPD. According to the
      results we have divided the patient population into two groups: I, those patients
      who showed improvement after treatment, and II: those patients who did not show
      improvement. We conducted a comparative statistical analysis of the
      epidemiologic, clinical, radiologic, and therapeutic parameters between the two
      groups. RESULTS: A total of 37 articles comprising with 58 cases were included
      for analysis with an average follow-up of 12 months. There were 36 patients in
      group I and 22 in group II. The average age was 57.8 years in group I and 54.3
      years in group II (P=0.32). Onset of symptoms was acute or subacute in 57% of
      patients in group I, and in 50% of patients in group II (P=0.62). Bulbar signs
      were present in 28% of cases in group I and in 36% of cases in group II (P=0.49).
      Hyperintensity of the brainstem on T2-weighted sequence magnetic resonance
      imaging was more common in patients in group II (78%) compared with patients in
      group I (45%) (P=0.012). Patients who underwent surgical procedure have shown
      good outcomes compared to patients treated with endovascular approach (P=0.039).
      CONCLUSIONS: The poor outcomes were correlated to the presence of brainstem
      signal abnormalities on magnetic resonance imaging, whereas the prognosis does
      not depend on age, sex, clinical presentation, or anatomic characteristics of the
      fistula.

PMID- 23010069
TI  - Right iliac aortic aneurysmal hemorrhage as a complication of lumbar discectomy.
AB  - BACKGROUND: Vascular injury is rarely reported but can be a life-threatening
      complication after lumbar disc surgery. CASE DESCRIPTION: We report a case of the
      rupture of a pseudoaneurysm of the right common iliac artery after spinal surgery
      for herniation of an intervertebral disc. It was successfully treated by prompt
      surgical repair. CONCLUSION: This case reminds us of this rare but possible
      complication, and emphasizes the importance of early diagnosis and urgent
      intervention.

PMID- 23010070
TI  - A 13-year analysis from Switzerland of non-fatal sledging (sledding or
      tobogganing) injuries.
AB  - INTRODUCTION: Winter sports have evolved from an upper class activity to a mass
      industry. Especially sledging regained popularity at the start of this century,
      with more and more winter sports resorts offering sledge runs. This study
      investigated the rates of sledging injuries over the last 13 years and analysed
      injury patterns specific for certain age groups, enabling us to make suggestions
      for preventive measures. METHODS: We present a retrospective analysis of
      prospectively collected data. From 1996/1997 to 2008/2009, all patients involved
      in sledging injuries were recorded upon admission to a Level III trauma centre.
      Injuries were classified into body regions according to the Abbreviated Injury
      Scale (AIS). The Injury Severity Score (ISS) was calculated. Patients were
      stratified into 7 age groups. Associations between age and injured body region
      were tested using the chi-squared test. The slope of the linear regression with
      95% confidence intervals was calculated for the proportion of patients with
      different injured body regions and winter season. RESULTS: 4956 winter sports
      patients were recorded. 263 patients (5%) sustained sledging injuries. Sledging
      injury patients had a median age of 22 years (interquartile range [IQR] 14-38
      years) and a median ISS of 4 (IQR 1-4). 136 (51.7%) were male. Injuries (AIS >=
      2) were most frequent to the lower extremities (n=91, 51.7% of all AIS >= 2
      injuries), followed by the upper extremities (n=48, 27.3%), the head (n=17,
      9.7%), the spine (n=7, 4.0%). AIS >= 2 injuries to different body regions varied
      from season to season, with no significant trends (p>0.19). However, the number
      of patients admitted with AIS >= 2 injuries increased significantly over the
      seasons analysed (p=0.031), as did the number of patients with any kind of
      sledging injury (p=0.004). Mild head injuries were most frequent in the youngest
      age group (1-10 years old). Injuries to the lower extremities were more often
      seen in the age groups from 21 to 60 years (p<0.001). CONCLUSION: Mild head
      trauma was mainly found in very young sledgers, and injuries to the lower
      extremities were more frequent in adults. In accordance with the current
      literature, we suggest that sledging should be performed in designated, obstacle
      free areas that are specially prepared, and that children should always be
      supervised by adults. The effect of routine use of helmets and other protective
      devices needs further evaluation, but it seems evident that these should be
      obligatory on official runs.

PMID- 23010071
TI  - Differential expressions of lysyl oxidase family in ACL and MCL fibroblasts after
      mechanical injury.
AB  - Lysyl oxidase (LOX) family has the capacity to catalyse the cross-linking of
      collagen and elastin, implicating its important fundamental roles in tissue
      development and injury healing. However, the variations in expression of the LOX
      family in the normal and injured anterior cruciate ligament (ACL) are not fully
      known. To better understand the role of LOX family in the self-healing inability
      mechanism of injured ACL, this study is to measure the LOX family's differential
      expressions in ACL and medial collateral ligament (MCL) fibroblasts after
      mechanical injury induced by using an equi-biaxial stretching chamber. The cells
      received various degrees of mechanical stretch 0% (resting state), 6%
      (physiological state) and 12% (injurious state), respectively. The gene profile
      and protein expressions were analysed by semi-quantitative PCR, quantitative real
      time PCR and Western blotting. At physiological state, gene expression showed LOX
      in ACL was 2.6-5.2 folds higher than that in MCL in all culture time periods,
      LOXL-4 1.2-3.6 folds, but LOXL-3 in MCL showed 1.1-4.8 folds higher than that in
      ACL. In injurious state, MCL gene expressions were 2.8-29.6 folds higher than ACL
      in LOX, LOXL-2, LOXL-3 and LOXL-4 at 2, 6 and 12h periods. These differential
      expression profiles of the LOX family in the two ligament tissues were further
      used to explain the intrinsic differences between ACL and MCL, and why injured
      ACL could not be amenable to repair itself, whereas MCL could.

PMID- 23010072
TI  - Early and ultra-early surgery in hip fracture patients improves survival.
AB  - BACKGROUND: Hip fracture is a common injury with associated high mortality.
      Recent drives by the Department of Health have sought to prioritise these
      patients' care. In April 2010, the Best Practice Tariff was introduced in England
      and Wales. This offers financial incentives to institutions that provide holistic
      care and surgery within 36h for hip fracture patients. The England and Wales
      National Institute for Health and Clinical Excellence (NICE) published its first
      guidance on hip fracture management in June 2011, and emphasised the need for
      surgery on the day or day after admission. In spite of the emphasis placed on
      this injury, the predictors of in-hospital mortality remain ill-defined. In
      particular the effect of the timing of surgery remains contentious. OBJECTIVE: To
      address the issues raised by NICE around surgical timing and examine whether
      surgery before a 36h watershed improves survival. In addition, to examine
      survival outcomes for each 12h watershed following admission. MATERIALS AND
      METHODS: Prospectively collected data on 2056 patients presenting to our unit
      with hip fractures between February 2008 and May 2011 were retrospectively
      reviewed. Multivariate regression analysis was used to correct for confounders,
      and so determine the effect of various parameters on in-patient mortality.
      RESULTS: Age (p<0.0001), male-gender (p<0.0001), source of admission (p<0.05),
      ASA-grade (p<0.0001) and delay of surgery (p<0.01) were associated with an
      increased risk of in-hospital mortality. The adjusted odds of in-hospital
      mortality were 1.58 (p<0.05) times higher in those undergoing surgery after 36h
      compared to surgery before this time. Early surgery (within 24h) resulted in
      reduced in-hospital mortality when compared to the 36h watershed. Similarly ultra
      early surgery (within 12h) was even better still (adjusted odds ratio 3.9
      p<0.05). CONCLUSIONS: Expeditious surgery is associated with improved patient
      survival. Other predictors of in-hospital mortality include age, gender, in
      hospital fracture and ASA-grade. Ultra-early surgery (within 12h) reduces risk of
      in-hospital mortality.

PMID- 23010073
TI  - Radiation-free distal locking of intramedullary nails: evaluation of a new
      electromagnetic computer-assisted guidance system.
AB  - Distal locking of intramedullary nails (IMNs) is a difficult part of
      intramedullary nailing (IMN) that could be time-consuming and expose the surgeon,
      the surgery personnel and the patient to a considerable amount of radiation as
      fluoroscopy is usually guiding the procedure. Utilization of electromagnetic
      fields for that purpose offers an attractive alternative. The SURESHOTTM Distal
      Targeting System (Smith & Nephew, Inc., Memphis, TN, USA) is a novel commercially
      available radiation-free aiming system that utilizes computerized electromagnetic
      field tracking technology for the distal locking of IMNs. In order to evaluate
      the efficacy of the system we conducted the present study. Nineteen patients (six
      females-thirteen males, mean age 39.5 years, range 17-85 years) with closed
      diaphyseal fracture of the femur (eight patients) or the tibia (eleven patients)
      were treated with IMN using the SURESHOTTM Distal Targeting System for the distal
      interlocking. All targeting attempts were successful at first try and followed by
      correct positioning of the screws. Mean time for distal locking of tibial IMNs
      (two screws) was 219sec (range 200-250sec). Mean time for distal locking of
      femoral IMNs (two screws) was 249 (range 220-330sec). In the current study the
      SURESHOTTM Distal Targeting System proved to be accurate, fast and easy to learn.

PMID- 23010074
TI  - In vitro neurotoxic Fe(III) and Fe(III)-chelator activities in rat hippocampal
      cultures. From neurotoxicity to neuroprotection prospects.
AB  - It is well known that iron dysregulation is involved in a number of processes
      involving genetic and non-genetic factors leading to neurodegeneration. Molecules
      bearing iron or influencing iron metabolism reflect directly into the levels of
      that redox active metal, present as Fe(II)/Fe(III), in the brain. In turn, iron
      level variations are associated with chemical reactivity disrupting iron
      homeostasis, generating variable neurotoxic iron forms and contributing to the
      vulnerability of cells toward oxidative stress and neuronal death in Alzheimer's
      disease (AD). Efforts to delineate the interactions of neurotoxic Fe(III) with
      low molecular mass substrates, relevant to cellular processes, led to the
      discovery of specific well-defined binary iron-quinate (FeQ) species. Poised to
      investigate the specific effects of a) well-defined forms of labile soluble
      Fe(III), b) the nature and chemistry of the ligand bound to Fe(III), and c) a
      natural metal ion binder - quinic acid - acting as a potential neuroprotectant
      toward iron toxicity, FeCl(3), FeQ, and free quinate were employed in in vitro
      studies involving primary rat hippocampal cultures. Three hour and 24-hour
      exposures of such cultures to Fe(III) reveal significant differential effects on
      both glial and neuronal cell survival linked to neurotoxicity of the specific yet
      variably composed complex forms of iron. The use of quinic acid both in the free
      and bound form to Fe(III) a) exemplifies essential structural and chemical
      attributes of naturally encountered metal ion binders promoting well-defined
      interactions with neurotoxic Fe(III), and b) signifies the potential linkage of
      labile Fe(III) chemical reactivity in neurodegeneration with natural substrate
      neuroprotection.

PMID- 23010075
TI  - Basal but not luminal mammary epithelial cells require PI3K/mTOR signaling for
      Ras-driven overgrowth.
AB  - The mammary ducts of humans and mice are comprised of two main mammary epithelial
      cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of
      luminal MECs. Breast cancer subtypes show divergent clinical behavior that may
      reflect properties inherent in their MEC compartment of origin. How the response
      to a cancer-initiating genetic event is shaped by MEC subtype remains largely
      unexplored. Using the mouse mammary gland, we designed organotypic three
      dimensional culture models that permit challenge of discrete MEC compartments
      with the same oncogenic insult. Mammary organoids were prepared from mice
      engineered for compartment-restricted coexpression of oncogenic H-RAS(G12V)
      together with a nuclear fluorescent reporter. Monitoring of H-RAS(G12V)
      expressing MECs during extended live cell imaging permitted visualization of Ras
      driven phenotypes via video microscopy. Challenging either basal or luminal MECs
      with H-RAS(G12V) drove MEC proliferation and survival, culminating in aberrant
      organoid overgrowth. In each compartment, Ras activation triggered modes of
      collective MEC migration and invasion that contrasted with physiologic modes used
      during growth factor-initiated branching morphogenesis. Although basal and
      luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies
      revealed divergent use of Ras effector pathways. Blocking either the
      phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely
      suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly
      attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype
      defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin
      may critically determine the drug sensitivity profiles of mammary neoplasia.

PMID- 23010076
TI  - Skin-test infiltrating lymphocytes early predict clinical outcome of dendritic
      cell-based vaccination in metastatic melanoma.
AB  - The identification of responding patients early during treatment would improve
      the capability to develop effective new immunotherapies more rapidly. Here, we
      describe a bioassay that may link early T-cell-mediated immune responses to later
      clinical benefits. This bioassay rests upon the tenet of immunotherapy that tumor
      specific effector T cells capable of invading peripheral tissue can recognize
      tumor antigens and exert cytotoxic functions there. To show its utility, we
      conducted a retrospective study of a large cohort of metastatic melanoma patients
      (n = 91) enrolled in dendritic cell (DC)-based vaccination protocols to examine a
      hypothesized correlation of posttreatment skin-infiltrating lymphocytes (SKIL)
      with overall survival (OS). Stringent immunologic criteria were defined to
      identify long-term survivors. The presence of tumor-associated antigen (TAA)
      specific CD8(+) T cell populations within SKILs (criterion I) was highly
      predictive for long-term survival. Further restriction by selecting for the
      presence of TAA-specific CD8(+) T cells specifically recognizing tumor peptide
      (criterion II) was also associated with improved OS. Recognition of naturally
      processed antigen (criterion III) maximized the accuracy of the test, with a
      median OS of 24.1 versus 9.9 months (P = 0.001). Our results show that detailed
      characterization of SKILs can permit an accurate selection of metastatic melanoma
      patients who benefit most from DC-based vaccination. This simple and robust
      bioassay integrates multiple aspects of cellular functions that mediate effective
      immune responses, thereby offering an effective tool to rapidly identify patients
      who are responding to immunotherapy at an early stage of treatment.

PMID- 23010077
TI  - Inactivation of the Dlc1 gene cooperates with downregulation of p15INK4b and
      p16Ink4a, leading to neoplastic transformation and poor prognosis in human
      cancer.
AB  - The tumor suppressor gene deleted in liver cancer-1 (DLC1), which encodes a
      protein with strong RhoGAP (GTPase activating protein) activity and weak Cdc42GAP
      activity, is inactivated in various human malignancies. Following Dlc1
      inactivation, mouse embryo fibroblasts (MEF) with a conditional Dlc1 knockout
      allele reproducibly underwent neoplastic transformation. In addition to
      inactivation of Dlc1 and increased activity of Rho and Cdc42, transformation
      depended on the subsequent decreased expression of the Cdk4/6 inhibitors
      p15(Ink4b) and p16(Ink4a) together with increased expression and activation of
      Cdk4/6. The level of expression of these cell-cycle regulatory genes was relevant
      to human tumors with low DLC1 expression. Analysis of publicly available
      annotated datasets of lung and colon cancer with gene expression microarray
      profiles indicated that, in pairwise comparisons, low DLC1 expression occurred
      frequently together (P < 0.01) with downregulation of p15(Ink4b) or p16(Ink4a) or
      upregulation of CDK4 or CDK6. In addition, an unfavorable prognosis (P < 0.05)
      was associated with low DLC1 and low p15(Ink4b) in lung cancer and colon cancer,
      low DLC1 and low p16(Ink4a) in lung cancer, low DLC1 and high CDK4 in lung
      cancer, and low DLC1 and high CDK6 in colon cancer. Thus, several genes and
      biochemical activities collaborate with the inactivation of DLC1 to give rise to
      cell transformation in MEFs, and the identified genes are relevant to human
      tumors with low DLC1 expression.

PMID- 23010078
TI  - Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy.
AB  - Microbubble contrast agents can specifically deliver nucleic acids to target
      tissues when exposed to ultrasound treatment parameters that mediate microbubble
      destruction. In this study, we evaluated whether microbubbles and ultrasound
      targeted microbubble destruction (UTMD) could be used to enhance delivery of EGF
      receptor (EGFR)-directed siRNA to murine squamous cell carcinomas. Custom
      designed microbubbles efficiently bound siRNA and mediated RNAse protection. UTMD
      mediated delivery of microbubbles loaded with EGFR-directed siRNA to murine
      squamous carcinoma cells in vitro reduced EGFR expression and EGF-dependent
      growth, relative to delivery of control siRNA. Similarly, serial UTMD-mediated
      delivery of EGFR siRNA to squamous cell carcinoma in vivo decreased EGFR
      expression and increased tumor doubling time, relative to controls receiving EGFR
      siRNA-loaded microbubbles but not ultrasound or control siRNA-loaded microbubbles
      and UTMD. Taken together, our results offer a preclinical proof-of-concept for
      customized microbubbles and UTMD to deliver gene-targeted siRNA for cancer
      therapy.

PMID- 23010079
TI  - Is collagen fiber damage the cause of early softening in articular cartilage?
AB  - OBJECTIVE: Because collagen damage and cartilage softening have not yet been
      determined simultaneously in one study for the very early onset of osteoarthritis
      (OA), it remains questionable whether they are associated. The aim of the present
      study is therefore to evaluate whether indeed, initial collagen damage can be
      found when tissue softening occurs as a result of excessive mechanical loading.
      METHODS: To investigate this aim, a series of specific indentation loading
      protocols were designed to induce and monitor cartilage softening in
      osteochondral explants of bovine carpometacarpal joints. The experiment contained
      one control group (n = 6) in which no damage was induced and four experimental
      groups in which samples received either a constant load of 3 (n = 5), 6 (n = 5)
      or 15 N (n = 6), or an increasing load (n = 7) from 2 to 13 N in 11 steps.
      Moreover, to determine mechanically induced collagen damage, Col2-3/4M
      (cumulative collagen damage) and Col2-3/4C(short) (only enzymatic damage)
      staining were compared. RESULTS: The normalized peak and equilibrium reaction
      forces decreased in the groups that received increasing and 15 N peak loading.
      However, Col2-3/4M staining was negative in all samples, while enzymatic damage
      (Col2-3/4C(short)) appeared similar in experiments and in unloaded control
      groups. CONCLUSION: It was shown that a loading magnitude threshold exists above
      which softening occurs in cartilage. However, in samples that did show softening,
      we were unable to detect collagen damage. Thus, our results demonstrate that
      cartilage softening most likely precedes collagen damage.

PMID- 23010080
TI  - Receiver-operating characteristics of adjusted urine measurements of oxycodone
      plus metabolites to distinguish between three different rates of oxycodone
      administration.
AB  - OBJECTIVES: In a study by Couto et al. (Use of an algorithm applied to urine drug
      screening to assess adherence to an oxycontin regimen. J Opioid Manag 2009;5:359
      64), adjusted urine measurements of oxycodone plus metabolites noroxycodone and
      oxymorphone were determined among volunteer subjects in three groups according to
      oxycodone administration rates (A: 80 mg/day; B: 160 mg/day; C: 240 mg/day). We
      performed receiver-operating characteristic (ROC) analyses of the distribution
      data from this study to determine the ability to correctly categorize individual
      measurements with respect to each group. DESIGN AND METHODS: For groups A-C,
      assumed reference ranges were defined as median-centered intervals encompassing a
      designated central percentage of the group's distribution. By varying assumed
      reference ranges across all possible reference ranges, ROC analyses of the
      ability of each group's reference ranges to appropriately include or exclude
      members of all groups were calculated. This generated six ROC curves (sensitivity
      vs. specificity): A vs. (B or C); B vs. (A or C); C vs. (A or B). RESULTS:
      Overlaps of distributions A, B, and C were large, such that none of the ROC
      curves exceeded areas-under-curves of 0.8. The greatest sensitivity-specificity
      combination had a sensitivity of 74% for C with specificity of 75% for A, for
      which oxycodone administration rates were different by a factor of 3.
      CONCLUSIONS: ROC analyses of data from a previous study demonstrated that, even
      under experimentally controlled conditions, adjusted urine drug measurements
      could not be used reliably to correctly categorize individual subjects' results
      according to their known oxycodone administration rates in the range of 80-240
      mg/day. Misclassifications of results were 25% or greater.

PMID- 23010081
TI  - Celecoxib induces proliferation and Amphiregulin production in colon
      subepithelial myofibroblasts, activating erk1-2 signaling in synergy with EGFR.
AB  - The COX-2 inhibitor Celecoxib, tested in phase III trials for the prevention of
      sporadic colon adenomas, reduced the appearance of new adenomas, but was unable
      to affect the incidence of colon cancer. Moreover the 5years follow-up showed
      that patients discontinuing Celecoxib treatment had an increased incidence of
      adenomas as compared to the placebo arm. In the APC(min/+) mouse model short term
      treatment with Celecoxib reduced gut adenomas, but a prolonged administration of
      the drug induced fibroblast activation and intestinal fibrosis with a final tumor
      burden. The way Celecoxib could directly activate human colon myofibroblasts (MF)
      has not yet been investigated. We found that MF are activated by non toxic doses
      of Celecoxib. Celecoxib induces erk1-2 and Akt phosphorylation within 5'. This
      short term activation is apparently insufficient to cause phenotypic changes, but
      the contemporary triggering of EGFR causes an impressive synergic effect inducing
      MF proliferation and the neo-expression and release of Amphiregulin (AREG), a
      well known EGFR agonist involved in colon cancer progression. As a confirm to
      these observations, the erk inhibitor U0126 and the EGFR inhibitors Tyrphostin
      and Cetuximab were able to contrast AREG induction. Our data provide evidence
      that Celecoxib directly activates MF empowering EGFR signaling. According to
      these results the association with EGFR (or erk1-2) inhibitors could abolish the
      off-target activity of Celecoxib, possibly extending the potential of this drug
      for colon cancer prevention.

PMID- 23010082
TI  - DNA methylome alterations in chemical carcinogenesis.
AB  - Carcinogenesis, a complex multifactorial process of the transformation of normal
      cells into malignant cells, is characterized by many biologically significant and
      interdependent alterations triggered by the mutational and/or non-mutational
      (i.e., epigenetic) events. One of these events, specific to all types of cancer,
      is alterations in DNA methylation. This review summarizes the current knowledge
      of the role of DNA methylation changes induced by various genotoxic chemicals
      (carcinogenic agents that interact with DNA) and non-genotoxic carcinogens
      (chemicals causing tumor by mechanisms other than directly damaging DNA) in the
      lung, colorectal, liver, and hematologic carcinogenesis. It also emphasizes the
      potential role for epigenetic changes to serve as markers for carcinogen exposure
      and carcinogen risk assessment. 

PMID- 23010083
TI  - Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and
      tumor formation of human glioblastoma cells in nude mice.
AB  - Glioblastoma is the most common and fatal type of primary brain tumors featured
      with hyperplastic blood vessels. Here, we performed meta-analyses of published
      data and established a correlation between high TIP-1 expression levels and the
      poor prognosis of glioblastoma patients. Next, we explored the biological
      relevance of TIP-1 expression in the pathogenesis of glioblastoma. By using
      orthotopic and heterotopic mouse models of human glioblastomas, this study has
      characterized TIP-1 as one contributing factor to the tumor-driven angiogenesis.
      In vitro and in vivo functional assays, along with biochemical analyses with
      microarrays and antibody arrays, have demonstrated that TIP-1 utilizes multiple
      pathways including modulating fibronectin gene expression and uPA protein
      secretion, to establish or maintain a pro-angiogenic microenvironment within
      human glioblastoma. In conclusion, this work supports one hypothesis that TIP-1
      represents a novel prognostic biomarker and a therapeutic target of human
      glioblastoma.

PMID- 23010084
TI  - A meta-analysis of randomized controlled trials comparing percutaneous coronary
      intervention with medical therapy in stable angina pectoris.
AB  - There continues to remain uncertainty regarding the effect of percutaneous
      coronary intervention (PCI) vs medical therapy in patients with stable angina. We
      therefore performed a systematic review and study-level meta-analysis of
      randomized controlled trials of patients with stable angina comparing PCI vs
      medical therapy for each of the following individual outcomes: all-cause
      mortality, cardiovascular (CV) mortality, myocardial infarction (MI), and angina
      relief. We used 8 strategies to identify eligible trials including bibliographic
      database searches of MEDLINE, PubMed, EMBASE, and the Cochrane Controlled Trials
      Registry until November 2011. Two independent reviewers undertook decisions about
      study eligibility and data abstraction. Data were pooled using a random effects
      model. Ten prospective randomized controlled trials fulfilled our eligibility
      criteria and they included a total of 6752 patients. We did not detect
      differences between PCI vs medical therapy for all-cause mortality (663 events;
      relative risk [RR], 0.97 [confidence interval (CI), 0.84-1.12]; I(2) = 0%), CV
      mortality (214 events; RR, 0.91 [CI, 0.70-1.17]; I(2) = 0%), MI (472 events; RR,
      1.09 [CI, 0.92-1.29]; I(2) = 0%), or angina relief at the end of follow-up (2016
      events; RR, 1.10 [CI, 0.97-1.26]; I(2)=85%). PCI was not associated with
      reductions in all-cause or CV mortality, MI, or angina relief. Considering the
      cost implication and the lack of clear clinical benefit, these findings continue
      to support existing clinical practice guidelines that medical therapy be
      considered the most appropriate initial clinical management for patients with
      stable angina.

PMID- 23010085
TI  - Canadian Society for Cardiovascular Magnetic Resonance (CanSCMR) recommendations
      for cardiovascular magnetic resonance image analysis and reporting.
AB  - Cardiovascular magnetic resonance (CMR) imaging is a rapidly developing
      technology that is becoming increasingly important in the diagnostic assessment
      of heart disease. Recognizing the need for recommendations to optimize the use of
      this technique, the Canadian Society for Cardiovascular Magnetic Resonance
      developed a task force to generate recommendations on the clinical use of
      parameters acquired by CMR imaging and how they should be reported. This article
      is the consensus report generated by the task force. The online material of this
      report provides such parameters for all relevant clinical settings, including
      pediatric and congenital applications. It considers the current clinical role of
      CMR, general requirements for CMR imaging, components of CMR studies,
      quantitative CMR image analysis, and appropriate contents of CMR reports. The
      recommendations are based on previously published recommendations on analysis and
      reporting and are the first of their kind. It is hoped that the use of these
      recommendations to guide daily clinical routine will help institutions offering
      CMR to adhere to high standards of quality according to the present state of the
      art.

PMID- 23010086
TI  - The representation of suicide on the Internet: implications for clinicians.
AB  - BACKGROUND: Suicide is one of the major causes of death in the world, leading to
      approximately 1 million deaths per year. While much of what is said about suicide
      and its causes is still taboo in most contemporary societies and cultures,
      internet websites and discussion forums have become an important and
      controversial source of information on the subject. A great deal of ambivalence
      is discernible as to whether online communication about suicide primarily should
      be seen as an opportunity or a serious threat. OBJECTIVE: To investigate how the
      subject of suicide is represented on the Internet, based on hits generated by the
      search engine Google. METHODS: In an exploratory design, Google search results on
      the target word "suicide", for the years 2005, 2009, and 2012 respectively, were
      systematically analyzed and compared. RESULTS: The study shows that web pages of
      institutional origin on the subject predominate, that the content provided by
      these institutions concerns primarily research and prevention, and that the form
      of communication used by these senders is almost exclusively monological.
      However, besides these institutional pages there are a substantial number of
      private senders and pages, often anti-medical and against treatment of depression
      and other mental problems, characterized by dialogue, confessions and narratives,
      and to a higher degree, an alternative pro-suicide stance. CONCLUSIONS: To
      counteract the influence of anti-medical and pro-suicide information, the role of
      the Internet should be discussed with the patient in clinical practice.
      Dialogical and confessional communications provide an opportunity for the
      clinician to gain a deeper perspective into perceptions of patients, regarding
      both their afflictions and the role of medical treatment in their lives.

PMID- 23010088
TI  - The impact of antibiotic impregnated PICC lines on the incidence of bacteremia in
      a regional burn center.
AB  - INTRODUCTION: Peripherally inserted central catheters (PICCs) have been used
      increasingly in burn patients who often have decreased intravascular volumes and
      obtaining intravascular access for resuscitative efforts can be difficult. A
      potentially serious complication is bloodstream infection. The purpose of our
      study is to examine the impact of antibiotic impregnated PICC lines on the
      bacteremia rate in a regional burn center. METHODS: Consecutive patients admitted
      to the burn unit and receiving an antibiotic impregnated PICC line were included
      in the study. Baseline demographics and bacteremia rate was recorded. A
      retrospective chart review was then undertaken of the 30 consecutive patients
      admitted to the burn unit and receiving a PICC line prior to the study period.
      RESULTS: Nineteen patients were enrolled over the two-year period. The bacteremia
      rate for the study group was 0% compared to the 50% bacteremia rate of the
      retrospective control group (p=<0.001). CONCLUSION: Antibiotic impregnated PICC
      lines decrease the bacteremia rate in our burn population. This has potential
      benefits for both patient morbidity and mortality as well as potential cost
      savings for the healthcare system.

PMID- 23010087
TI  - Surgical staple as a transcutaneous transducer for ECG electrodes in burnt skin:
      safe surgical monitoring in major burns.
AB  - It is often difficult to apply traditional ECG electrodes on patients with
      extensive burns due to a large operative site, compromise of sterility, the fact
      that traditional placement would be within the operative site or because stick-on
      pads cannot stick due to prep solution, bleeding and other factors. We present an
      effective solution based on our experience, of using a common staple or "clip"
      where the ECG electrode is attached. We can see the patient in the prone position
      with the back having been debrided and grafted. This technical improvisation
      gives clinicians the ability to monitor safely and accurately the patients'
      physiological parameters.

PMID- 23010089
TI  - Why do some like it hot? Genetic and environmental contributions to the
      pleasantness of oral pungency.
AB  - Although potential environmental influences on hedonic responses to oral pungency
      have been identified, little is known of the possible role of genetics underlying
      these responses. We explored the contribution of genetic and environmental
      influences on the pleasantness of oral pungency and spicy foods. Respondents were
      young adult Finnish twins (n=331, 21-25 years), including 47 complete monozygotic
      and 93 dizygotic twin pairs and 51 twin individuals without their co-twin.
      Pleasantness and intensity of strawberry jelly spiked with capsaicin (0.0001%
      w/v) relative to untainted strawberry jelly were rated. Furthermore, pleasantness
      of spicy foods and oral pungency caused by spices were rated based on food names
      in a questionnaire. Respondents were grouped as non-likers, medium-likers, and
      likers by their pleasantness responses to capsaicin spiked jelly. The
      contribution of genetic and environmental factors to variation and co-variation
      of the pleasantness traits was analyzed using quantitative genetic modeling. The
      non-likers perceived oral pungency as more intense (sensory) and rated
      pleasantness of spicy foods and pungent sensations caused by spices
      (questionnaire) as less pleasant than the likers. Genetic factors accounted for
      18-58% of the variation in the pleasantness of oral pungency, spicy foods and
      pungent sensations. The rest was due to environmental factors. All pleasantness
      traits (sensory and questionnaire based) were shown to share a common genetic
      variance. This indicates that an underlying genetic aptitude to like oral
      pungency, and spicy foods exists and it is expressed in these measures. The
      findings broaden the understanding of the diverse nature of individual food
      preferences and motivate further search for the underlying genetic components of
      oral pungency.

PMID- 23010090
TI  - Titanium-treated surroundings attenuate psychological stress associated with
      autonomic nerve regulation in office workers with daily emotional stress.
AB  - Housing mice in the presence of small particles of titanium has been shown to
      reduce stress-responsive behavior via the autonomic nervous system. Here, we
      examined the effects of nighttime titanium exposure on stress parameters and
      autonomic nerve activity in office workers with emotional stress. A randomized
      double-blind, placebo controlled trial was performed in 24 male subjects with
      desk jobs, who were randomly allocated to spend 5 nights in rooms with or without
      titanium. The serum concentrations of stress-responsive hormones (cortisol,
      adrenocorticotropin, and catecholamine) were measured, and profiles of emotional
      stress were collected to subjectively assess relaxation. Autonomic nerve activity
      was examined by power spectra analysis of heart rate variability. In
      psychological tests, factors related to tension (-14.5%, 95% CI=-15.7--2.1),
      anger (-11.3%, 95% CI=-13.9--0.7), and emotional stress (-28.5%, 95% CI=-30.0-
      5.3) were significantly decreased by exposure to titanium. The serum level of
      adrenocorticotropin was gradually elevated throughout the experimental period in
      the placebo group (day 4, 80.5%, 95% CI=7.1-37.5 vs. before trial) but not the
      titanium group. Power spectral analysis of R-R interval data showed a significant
      elevation in the high-frequency power spectral ratio in subjects housed in
      titanium rooms (days 1-2, 14.3%, 95% CI=4.7-21.9; days 3-4, 26.8%, 95% CI=4.9
      38.7; and days 5-6, 24.1%, 95% CI=5.8-34.0 vs. before trial). These results
      suggest that sleeping in a room containing titanium lowers physiological and
      psychological stress.

PMID- 23010091
TI  - In vivo microvascular mosaics show air embolism reduction after perfluorocarbon
      emulsion treatment.
AB  - Massive arteriolar gas embolism (AGE) has never been evaluated in vivo using
      intravital microscopy and previous perfluorocarbon (PFC) emulsions were only
      effective in AGE when administered before AGE. We implemented a new system for
      quantitative studies of massive AGE using brightfield microscopy and tested a
      treatment with a third-generation PFC emulsion after massive AGE. We studied
      bubble dynamics in cremaster muscles from anesthetized rats after AGE was induced
      by direct air injection into the femoral artery ipsilateral to the studied
      muscle. Using a motorized microscope stage and a color camera, in vivo
      microvascular mosaics were produced on-line from over 2000 digital images to
      evaluate multiple networks in order to investigate the distribution, lodging,
      breaking, reduction and moving of 105 air bubbles in microvessels. Thirty minutes
      after PFC treatment, there was a reduction of 80% in bubble volume while
      untreated and saline-treated rats showed significantly smaller decreases of 33%
      and 40%, respectively (p<0.05). Air bubbles also dissolved into a larger number
      of smaller bubbles after PFC treatment. The proposed methodology may prove useful
      for rapid in vivo data acquisition from large networks. Since large air bubbles
      broke-up, decreased in length and volume, and moved toward smaller microvessels,
      the study provides quantitative data to support a mechanism by which PFC may
      improve tissue blood flow following massive AGE. The findings suggest that this
      new generation of PFC emulsions administered after severe AGE may reach
      compromised microvascular networks and provide help to alleviate microvascular
      obstruction by increasing air bubble reabsorption.

PMID- 23010092
TI  - Combined SCLC clinical and pathologic characteristics.
AB  - INTRODUCTION: Despite the well characterized clinical course of 'pure' SCLC,
      there have not been many data on combined SCLC, ie, tumors, which contain both
      small-cell and non-small-cell components. MATERIALS AND METHODS: We analyzed 1628
      consecutive cases of lung cancer (1200 NSCLC, 428 SCLC) at our institution over
      the past decade. We identified 22 patients with C-SCLC. The pathologic and
      clinical characteristics of these patients were reviewed. Survival analysis was
      performed and prognostic factors were assessed. These data were compared with the
      results obtained from our 406 pure SCLC patients who presented during the same
      time period. RESULTS: The most common pathology was combined small-cell and large
      cell with 16 cases followed by combined small- and squamous-cell carcinoma (3
      cases), 2 cases of small-cell and nonspecified NSCLC, and 1 case of small cell
      and adenocarcinoma. Overall survival was significantly higher in C-SCLC patients
      compared with pure SCLC (median 15 vs. 10.8 months; P = .035). Surgery was
      significantly more common in this group of patients (45% vs. 3% in the pure small
      cell group; P < .0001). No difference in overall survival was observed in
      patients with C-SCLC and patients with pure SCLC, that did not receive surgery (P
      = .64). CONCLUSION: Patients with combined SCLC carry a better prognosis than
      those with pure small-cell variety and are more likely to undergo surgery.

PMID- 23010093
TI  - [Gait instability revealing a syndrome of inappropriate antidiuretic hormone
      secretion associated to pregabalin].
AB  - Pregabalin, a molecule with similar structure of GABA neurotransmitter, initially
      developed as an antiepileptic, is now commonly used in the treatment of painful
      peripheral neuropathies. We report an 82-year-old man who presented with
      confusion, urinary incontinence and gait instability. He was receiving pregabalin
      for a left L5 radicular pain. Laboratory tests at admission revealed a profound
      hyponatremia (117 mmol/L) that was corrected by fluid restriction and pregabalin
      withdrawal. According to the patient and laboratory outcome, we established the
      diagnosis of inappropriate antidiuretic hormone secretion due to pregabalin. The
      test of Naranjo demonstrated a probable imputability of pregabalin.

PMID- 23010095
TI  - Guest editorial--polyphenols and health (ICPH2011).

PMID- 23010096
TI  - Outdoor built environment barriers and facilitators to activity among midlife and
      older adults with mobility disabilities.
AB  - PURPOSE: To gain better understanding of how the built environment impacts
      neighborhood-based physical activity among midlife and older adults with mobility
      disabilities. DESIGN AND METHODS: We conducted in-depth interviews with 35 adults
      over age 50, which used an assistive device and lived in King County, Washington,
      U.S. In addition, participants wore global positioning systems (GPS) devices for
      3 days prior to the interview. The GPS maps were used as prompts during the
      interviews. Open coding of the 35 interviews using latent content analysis
      resulted in key themes and subthemes that achieved consensus between coders. Two
      investigators independently coded the text of each interview. RESULTS:
      Participants were on average of 67 years of age (range: 50-86) and predominantly
      used canes (57%), walkers (57%), or wheelchairs (46%). Key themes pertained to
      curb ramp availability and condition, sidewalk availability and condition, hills,
      aesthetics, lighting, ramp availability, weather, presence and features of
      crosswalks, availability of resting places and shelter on streets, paved or
      smooth walking paths, safety, and traffic on roads. IMPLICATIONS: A variety of
      built environment barriers and facilitators to neighborhood-based activity exist
      for midlife and older adults with mobility disabilities. Preparing our
      neighborhood environments for an aging population that uses assistive devices
      will be important to foster independence and health.

PMID- 23010097
TI  - Adult-onset Still's disease: clinical, serological and therapeutic
      considerations.
AB  - OBJECTIVES: This paper aims to describe the clinical manifestations, laboratory
      abnormalities and treatment of adult-onset Still's disease (AOSD) in Greek
      patients. METHODS: This is a retrospective observational study. Forty-four
      patients, diagnosed with AOSD, followed since 1985 up to June 2011, were
      included. The disease course and treatment were recorded and compared to
      previously published studies. RESULTS: Twenty-one males and 23 females were
      identified. Mean age at diagnosis was 38.3 years. The most common clinical
      manifestations were fever (100%), arthralgias (97.7%), arthritis (93.2%), salmon
      coloured rash (84%), myalgias (50%) and sore throat (38.6%). Characteristic
      laboratory abnormalities were leucocytosis with neutrophilia (81.8%), elevated C
      reactive protein (100%) and erythrocyte sedimentation rate (100%). Elevated liver
      enzymes and hyperferritinaemia were found in 50% and in 59% of the patients
      respectively. Very high ferritin serum levels (>5000 MUg/l) were found in 22.7%.
      Rheumatoid factor and antinuclear antibodies were negative in all patients.
      Thirty patients (68.2%) received non-steroidal anti-inflammatory drugs or aspirin
      with or without corticosteroids. Response to corticosteroids was common (58.9%).
      When this treatment was ineffective, a disease-modifying anti-rheumatic drug
      (DMARD), usually methotrexate, was added with a response rate of 63.6%. Anakinra
      was used in cases resistant to conventional immunosuppressive treatment. Ten out
      of 44 patients (22.7%) were treated with anakinra and response was achieved in
      all of them. CONCLUSIONS: Our results regarding clinical manifestations and
      laboratory abnormalities were similar to those of previous reports. High ferritin
      serum levels were reported in all studies of AOSD and are considered as
      diagnostically valuable. When treatment with corticosteroids and DMARDS had
      failed, biologic agents such as anakinra were successfully applied.

PMID- 23010098
TI  - Who is he and what is he to you? Recognition in Drosophila melanogaster.
AB  - The inability to discriminate friend from foe or the 'one' among many potential
      mates can have immediate life-threatening consequences or a long-term
      evolutionary impact. Successful social interactions depend on the ability to
      recognize and identify individuals within a social context. Once recognition
      occurs, a repertoire of behavioral responses becomes available and choices are
      made as interactions between individuals unfold. The vinegar fly, Drosophila
      melanogaster, displays a wide range of social activities and patterns of social
      interaction. If a male fly is unable to recognize other males or distinguish them
      from females, he may attempt to court both males and females alike, wasting
      energy and reducing his fitness. We review recent studies on the mechanisms of
      social recognition in this organism that pertain to both sides of an interaction:
      the generation of signals by one individual and the receiving and processing of
      these signals by others.

PMID- 23010094
TI  - 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with
      cervical length less than 30 mm.
AB  - OBJECTIVE: We sought to evaluate whether 17 alpha-hydroxyprogesterone caproate
      (17-OHP) reduces preterm birth (PTB) in nulliparous women with a midtrimester
      cervical length (CL) <30 mm. STUDY DESIGN: In this multicenter randomized
      controlled trial, nulliparous women with a singleton gestation between 16 and 22
      3/7 weeks with an endovaginal CL <30 mm (<10th percentile in this population)
      were randomized to weekly intramuscular 17-OHP (250 mg) or placebo through 36
      weeks. The primary outcome was PTB <37 weeks. RESULTS: The frequency of PTB did
      not differ between the 17-OHP (n = 327) and placebo (n = 330) groups (25.1% vs
      24.2%; relative risk, 1.03; 95% confidence interval, 0.79-1.35). There also was
      no difference in the composite adverse neonatal outcome (7.0% vs 9.1%; relative
      risk, 0.77; 95% confidence interval, 0.46-1.30). CONCLUSION: Weekly 17-OHP does
      not reduce the frequency of PTB in nulliparous women with a midtrimester CL <30
      mm.

PMID- 23010100
TI  - Left atrial appendage occlusion for stroke prevention.
AB  - Atrial fibrillation (AF) remains the most common arrhythmia encountered in
      clinical practice. One of its most devastating complication is the development of
      thromboembolism leading to stroke. The left atrial appendage (LAA) has been shown
      to be the site of thrombus formation in the majority of strokes associated with
      AF. Anticoagulation with warfarin has been the treatment of choice for prevention
      of embolic events in these patients, but it does have significant limitations
      including bleeding, need for continued follow-up blood tests, and drug-drug
      interactions. Although newer anticoagulants have been developed, they still have
      the potential side effect of causing significant bleeding. Closure or exclusion
      of the LAA has emerged as an alternative therapeutic approach to medical therapy.
      The aim of this article is to review the anatomy and physiology of the LAA,
      discuss the various treatment strategies for stroke prevention, review the
      current devices and technologies available for LAA occlusion, and discuss some of
      the more recent data available on these technologies.

PMID- 23010101
TI  - The stakeholder-consultation process in developing training and awareness-raising
      material within the framework of the EU Directive on Sustainable Use of
      Pesticides: the case of the EU-project BROWSE.
AB  - In September 2009, the Council of the European Union adopted the Directive on
      Sustainable Use of Pesticides (SUD). The core idea is that in order to achieve
      sustainable use of pesticides, it is necessary that everyone is conscious about
      the risks to both human health and the environment associated with the use of
      plant protection products. Therefore, in the SUD, training and raising awareness
      play key roles in order to achieve the objectives of the directive. In this
      sense, the European-founded project BROWSE (Bystanders, Residents, Operators and
      WorkerS Exposure models for plant protection products) has, as one of its main
      objectives, to contribute to the implementation of the SUD through the
      development and dissemination of communication materials for training and raising
      awareness. For this reason, a consultation process was implemented involving all
      relevant stakeholders in order to identify their opinions regarding the subjects
      to be prioritised, the factors influencing pesticide exposure to be focused on
      and the most suitable formats to develop training and awareness-raising material
      as well as identification of target groups. To collect the required information,
      participants were asked to answer an electronic questionnaire (giving the
      possibility through several debates for additional comments). The collected
      findings and the ensuing debates are described in this article and are going to
      be taken into account in the development of the BROWSE training and communication
      material for the raising of awareness.

PMID- 23010102
TI  - Arsenic species in broiler (Gallus gallus domesticus) litter, soils, maize (Zea
      mays L.), and groundwater from litter-amended fields.
AB  - Manure and bedding material (litter) generated by the broiler industry (Gallus
      gallus domesticus) often contain high levels of arsenic (As) when organoarsenical
      roxarsone and p-arsanilic acid are included in feed to combat disease and improve
      weight gain of the birds. This study was conducted to determine As levels and
      species in litter from three major broiler producing companies, and As levels in
      soils, corn tissue (Zea mays L.), and groundwater in fields where litter was
      applied. Total As in litter from the three different integrators ranged between
      <1 and 44 mg kg(-1). Between 15 and 20% of total As in litter consisted of mostly
      of arsenate, with smaller amounts of roxarsone and several transformation
      products that were extractable with phosphate buffer. Soils amended with litter
      had higher levels of bioavailable As (extractable with Mehlich 3 solution and
      taken up by corn leaves). Arsenic concentrations in plant tissue and groundwater,
      however, were below the World Health Organization thresholds, which was
      attributed to strong sorption/precipitation of arsenate in Fe- and Al-rich soils.
      Ecological impacts of amending soils with As-laden litter depend on the As
      species in the litter, and chemical and physical properties of soil that strongly
      affect As mobility and bioavailability in the environment.

PMID- 23010103
TI  - Immune cells and cardiovascular health in premenopausal women of rural India
      chronically exposed to biomass smoke during daily household cooking.
AB  - Changes in cells of the immune system are important indicators of systemic
      response of the body to air pollution. The aim of this study was to investigate
      the immunological changes in rural women who have been cooking exclusively with
      biomass for the past 5 years or more and compare the findings with women cooking
      exclusively with liquefied petroleum gas (LPG). We conducted a cross-sectional
      analysis of the associations between indices of indoor air pollution (IAP) and a
      set of immune assays. Biomass users illustrated marked suppression in the total
      number of T-helper (CD4+) cells and B (CD19+) cells while appreciable rise was
      documented in the number of CD8+ T-cytotoxic cells and CD16+CD56+ natural killer
      (NK) cells. A consistent finding among biomass users was rise in regulatory T
      (Treg) cells. Among biomass users, peripheral lymphocyte subpopulations, Treg
      cells, and the number of typical monocytes (CD16-CD64+ cells), antigen presenting
      types (CD16+CD64- cells) and plasmacytoid cells (CD16-CD64- cells) were found to
      be significantly altered in those who daily cooked with dung in comparison to
      wood and crop residue users (p<0.05). Biomass users who cooked in kitchens
      adjacent to their living areas had significant changes in peripheral lymphocyte
      subpopulations, typical monocytes (CD16-CD64+) with high phagocytic activity and
      antigen presenting monocytes (CD16+CD64-) against women who cooked in separate
      kitchens (p<0.01). This study has shown that women who cooked exclusively with
      biomass fuel had alterations in immune defense compared with their neighbors who
      cooked with LPG.

PMID- 23010104
TI  - For whom the bell tolls: distress signals from long-lived osteocytes and the
      pathogenesis of metabolic bone diseases.
AB  - Osteocytes are long-lived and far more numerous than the short-lived osteoblasts
      and osteoclasts. Immured within the lacunar-canalicular system and mineralized
      matrix, osteocytes are ideally located throughout the bone to detect the need
      for, and accordingly choreograph, the bone regeneration process by independently
      controlling rate limiting steps of bone resorption and formation. Consistent with
      this role, emerging evidence indicates that signals arising from apoptotic and
      old/or dysfunctional osteocytes are seminal culprits in the pathogenesis of
      involutional, post-menopausal, steroid-, and immobilization-induced osteoporosis.
      Osteocyte-originated signals may also contribute to the increased bone fragility
      associated with bone matrix disorders like osteogenesis imperfecta, and perhaps
      the rapid reversal of bone turnover above baseline following discontinuation of
      anti-resorptive treatments, like denosumab.

PMID- 23010106
TI  - A case-control study of fractures in men with idiopathic osteoporosis: fractures
      are associated with older age and low cortical bone density.
AB  - OBJECTIVES: To determine biochemical, radiological and micro-architectural bone
      factors related to fragility fractures in idiopathic male osteoporosis (IMO)
      patients. IMO is a rare disorder characterized by low areal bone mineral density
      (aBMD) (Z-score<-2) occurring in men after excluding secondary causes of low BMD.
      METHODS: We conducted a case-control study in 31 patients with fragility fracture
      (IMO F+) that had occurred after the age of 40 years and 37 without fracture (IMO
      F-). We first compared IMO group to 40 age-matched disease-free men. We measured
      aBMD and bone micro-architectural indices at distal radius and tibia sites with a
      HR-pQCT scan (XtremeCT) using standard and extended cortical analysis. Urine and
      blood samples were collected in order to determine the levels of bone-turnover
      markers and the potential determinant of bone fragility. Models of analysis of
      covariance, including age, height and weight as adjustment factors, were used to
      compare the groups. RESULTS: Compared to their controls, IMO patients showed
      marked disturbance of their micro-architectural parameters at tibia and radius
      affecting both trabecular and cortical parameters. IMO F+ subjects were
      significantly older than IMO F- subjects (58 +/- 8 vs. 53 +/- 9 yrs, p=0.01). BMD
      Z-score at the total-hip was significantly lower in IMO F+ (-1.3 +/- 0.5 vs. -0.9
      +/- 0.8 g/cm(2), p=0.01). After adjustment, trabecular micro-architectural
      parameters, biochemical markers and hormonal parameters were not different in the
      2 groups. At distal tibia, cortical v-BMD was significantly lower in IMO F+
      patients (799 +/- 73 vs. 858 +/- 60 mg/cm(3), p=0.03), while cortical thickness
      was not different. CONCLUSION: Our results show that patients with IMO display a
      marked disturbance of trabecular and cortical bone micro-architecture, and that
      age and low cortical density are determinants of the fracture occurrence.

PMID- 23010107
TI  - Influence of size scale and morphology on antibacterial properties of ZnO powders
      hydrothemally synthesized using different surface stabilizing agents.
AB  - Metal oxide nanoparticles represent a new class of important materials that are
      increasingly being developed for use in research and health-related applications.
      Although the antibacterial activity and efficiency of bulk zinc oxide were
      investigated in vitro, the knowledge about the antibacterial activity of ZnO
      nanoparticles remains deficient. In this study, we have synthesized ZnO particles
      of different sizes and morphologies with the assistance of different types of
      surface stabilizing agents - polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA)
      and poly (alpha,gamma, l-glutamic acid) (PGA) - through a low-temperature
      hydrothermal procedure. The characterization of the prepared powders was
      preformed using X-ray diffraction (XRD) method and field emission scanning
      electron microscopy (FE SEM), as well as Malvern's Mastersizer instrument for
      particle size distribution. The specific surface area (SSA) of the ZnO powders
      was measured by standard Brunauer-Emmett-Teller (BET) technique. The
      antibacterial behavior of the synthesized ZnO particles was tested against gram
      negative and gram-positive bacterial cultures, namely Escherichia coli (E. coli)
      and Staphylococcus aureus (S. aureus), respectively. We compared the results of
      the antibacterial properties of the synthesized ZnO samples with those of the
      commercial ZnO powder. According to the obtained results, the highest microbial
      cell reduction rate was recorded for the synthesized ZnO powder consisting of
      nanospherical particles. In all of the examined samples, ZnO particles
      demonstrated a significant bacteriostatic activity.

PMID- 23010105
TI  - MMP9 regulates the cellular response to inflammation after skeletal injury.
AB  - Like other tissue injuries, bone fracture triggers an inflammatory response,
      which plays an important role in skeletal repair. Inflammation is believed to
      have both positive and negative effects on bone repair, but the underlying
      cellular mechanisms are not well understood. To assess the role of inflammation
      on skeletal cell differentiation, we used mouse models of fracture repair that
      stimulate either intramembranous or endochondral ossification. In the first
      model, fractures are rigidly stabilized leading to direct bone formation, while
      in the second model, fracture instability causes cartilage and bone formation. We
      compared the inflammatory response in these two mechanical environments and found
      changes in the expression patterns of inflammatory genes and in the recruitment
      of inflammatory cells and osteoclasts. These results suggested that the
      inflammatory response could influence skeletal cell differentiation after
      fracture. We then exploited matrix metalloproteinase 9 (MMP9) that is expressed
      in inflammatory cells and osteoclasts, and which we previously showed is a
      potential regulator of cell fate decisions during fracture repair. Mmp9(-/-) mice
      heal stabilized fractures via endochondral ossification, while wild type mice
      heal via intramembranous ossification. In parallel, we observed increases in
      macrophages and T cells in the callus of Mmp9(-/-) compared to wild type mice. To
      assess the link between the profile of inflammatory cells and skeletal cell fate
      functionally, we transplanted Mmp9(-/-) mice with wild type bone marrow, to
      reconstitute a wild type hematopoietic lineage in interaction with the Mmp9(-/-)
      stroma and periosteum. Following transplantation, Mmp9(-/-) mice healed
      stabilized fractures via intramembranous ossification and exhibited a normal
      profile of inflammatory cells. Moreover, Mmp9(-/-) periosteal grafts healed via
      intramembranous ossification in wild type hosts, but healed via endochondral
      ossification in Mmp9(-/-) hosts. We observed that macrophages accumulated at the
      periosteal surface in Mmp9(-/-) mice, suggesting that cell differentiation in the
      periosteum is influenced by factors such as BMP2 that are produced locally by
      inflammatory cells. Taken together, these results show that MMP9 mediates
      indirect effects on skeletal cell differentiation by regulating the inflammatory
      response and the distribution of inflammatory cells, leading to the local
      regulation of periosteal cell differentiation.

PMID- 23010108
TI  - Synthesis and cellular compatibility of Co-doped ZnO particles in silk-fibroin
      peptides.
AB  - Co-doped ZnO particles were successfully prepared via a facile biomineralization
      process in the template of silk-fibroin (SF) peptides at room temperature, and SF
      peptides were coated onto the surface of particles. The ratio of Zn/Co in
      reactive solution could substantially influence the morphology of as-prepared
      particles, and the rough spherical particles including some nanoparticles of 50
      nm diameters could be obtained at 4:1 ratio of Zn/Co. The saturation
      magnetization of SF-coated Co-ZnO particles was 8.63 emu/g, much larger than that
      of Co-ZnO without SF. L929 cell test revealed that the Co-doped ZnO particles had
      a good cellular compatibility at the concentration of less than 0.25 mg/mL due to
      silk-peptide coating, indicating that the prepared Co-doped ZnO particles have a
      potential for the biomedical applications.

PMID- 23010109
TI  - A novel 'green' synthesis of colloidal silver nanoparticles (SNP) using Dillenia
      indica fruit extract.
AB  - In the present research we have defined a novel green method of silver
      nanoparticles synthesis using Dillenia indica fruit extract. D. indica is an
      edible fruit widely distributed in the foothills of Himalayas and known for its
      antioxidant and further predicted for cancer preventive potency. The maximum
      absorbance of the colloidal silver nanoparticle solution was observed at 421 nm
      when examined with UV-vis spectrophotometer.

PMID- 23010110
TI  - Immobilization of lipase on amino-cyclodextrin functionalized carbon nanotubes
      for enzymatic catalysis at the ionic liquid-organic solvent interface.
AB  - Amino-cyclodextrin was covalently attached to multiwalled carbon nanotubes
      (MWNTs). The functionalized MWNTs have a good dispersibility in water. The lipase
      was adsorbed onto the functionalized MWNTs. The immobilized lipase was utilized
      for the resolution of the model compound (R, S)-1-phenyl ethanol in heptane, the
      ionic liquid [Bmim]PF(6) as well as the heptane/[Bmim]PF(6) mixture. In the
      reaction media, the enzymatic activity of the immobilized lipase is much higher
      than that of the native lipase. In comparison to the catalysis in the ionic
      liquid and heptane, when using the mixture of heptane/[Bmim]PF(6) as the reaction
      medium, the catalysis by the immobilized lipase at the heptane-ionic liquid
      interface exhibited a higher catalysis activity. This is due to two aspects: the
      continuous diffusion of substrate from the heptane phase to the ionic liquid
      phase; the simultaneous extraction of product from the ionic liquid phase. In
      addition, the interfacial enzymatic catalysis facilitates the reuse of the
      immobilized lipase and the ionic liquid.

PMID- 23010111
TI  - Immobilizing silver nanoparticles (SNP) on Musa balbisiana cellulose.
AB  - Cellulose from Musa balbisiana was purified. A part of it was dispersed in
      distilled water using ultrasonication. The silver nanoparticles (SNP) were
      synthesized in the colloidal cellulose solution and stability of the
      nanoparticles was tested using UV-Vis spectrophotometer. Further characterization
      of the composite was done using spectral analysis by Fourier Transform Infrared
      Spectroscopy (FTIR) to reveal any bond formation between silver nanoparticles
      with M. balbisiana cellulose. Here we found that cellulose/silver nanoparticle
      colloid is stable for 29 days and there is no chemical interaction of cellulose
      with silver nanoparticles.

PMID- 23010112
TI  - Studies of Fe3O4/Ag/Au composites for immunoassay based on surface plasmon
      resonance biosensor.
AB  - A novel method immunosensor based on chemically functionalized Fe(3)O(4)/Ag/Au
      nanocomposite was developed. Fe(3)O(4)/Ag seeds were coated with Au and
      Fe(3)O(4)/Ag/Au nanocomposites were obtained. The nanocomposites could be
      obtained without violent stirring and the operation was easy and convenient. The
      magnetic nanocomposites can be easily immobilized on Au film of the surface
      plasmon resonance (SPR) biosensor with a magnetic pillar. The immobilization of
      Fe(3)O(4)/Ag/Au nanocomposites on the Au film leads to a large shift in resonance
      wavelength, which is due to the increase of the sensing membrane thickness, high
      dielectric constant of Ag and Au particles, and electromagnetic coupling between
      Fe(3)O(4)/Ag/Au nanocomposites and the Au film. The effects of Fe(3)O(4)/Ag/Au
      nanocomposites on the sensitivity of SPR biosensor were also investigated. As a
      result, the biosensor based on Au film shows a response for dog IgG in the
      concentration range of 1.25-20.00 MUg ml(-1), whereas the SPR biosensor based on
      Fe(3)O(4)/Ag/Au nanocomposites shows a response for dog IgG in the concentration
      range of 0.15-40.00 MUg ml(-1). The sensitivity of the SPR biosensor based on
      Fe(3)O(4)/Ag/Au nanocomposites is higher than that based on Au film.

PMID- 23010113
TI  - Development and optimization of multiparticulate drug delivery system of
      alfuzosin hydrochloride.
AB  - The purpose of present research was to develop and optimize sustained release
      floating pellets of alfuzosin hydrochloride which has narrow absorption window in
      proximal intestine to improve patient compliance and therapeutic efficacy in the
      treatment of benign prostatic hyperplasia. The system was designed to provide
      drug loaded pellets coated with three successive coatings over Celphere((r))
      (microcrystalline cellulose pellets) - drug layer, effervescent layer (HPMC and
      sodium bicarbonate) and gas entrapped polymeric membrane (Kollicoat((r)) SR 30D).
      A 3(2) factorial design was employed with HPMC:sodium bicarbonate and
      Kollicoat((r)) SR 30D concentration as independent variables while drug release
      and floating lag time were the dependent variables. Regression analysis was
      performed to identify best formulation conditions. Scanning electron microscopy
      was used to study pellet morphology. The floating ability and in vitro drug
      release of the system were dependent on amount of sodium bicarbonate layered onto
      pellets and coating level of Kollicoat((r)) SR 30D.

PMID- 23010114
TI  - The influence of plant stanol (beta-sitostanol) on inner leaflet of human
      erythrocytes membrane modeled with the Langmuir monolayer technique.
AB  - The presence of dietary phytocompounds - plant sterols and stanols - in human
      plasma and membranes raises the question on their influence on membrane
      properties. A good way to get an insight into interactions of these biomolecules
      with membranes at molecular level is to perform experiments on artificial
      systems, e.g. Langmuir monolayers, composed of membrane lipids. In this paper the
      influence of plant stanol - beta-sitostanol - on monolayers imitating the inner
      leaflet of human membrane, composed of phosphatidylethanolamine
      (POPE)/phosphatidylserine (POPS)/cholesterol (Chol) was studied. Two effects have
      been investigated and compared, namely the systematic increase of plant stanol
      (beta-sitostanol) content in the mixed film as well as the replacement of
      cholesterol by beta-sitostanol in POPE/POPS/Chol monolayer. The analysis of the
      collected data evidenced that the plant stanol strongly influences the
      condensation and interactions in POPE/POPS/Chol film. BAM images taken for the
      studied monolayers demonstrated that the presence of beta-sitostanol in the
      mixture leads to the formation of 3D crystallites within the film, which seems to
      result from a limited solubility of plant stanol in phospholipids environment.
      All these effects have got intensified upon systematic elimination of cholesterol
      and its replacement by plant stanol in the mixed monolayer. The obtained results
      evidence that the presence of plant stanol may significantly alter organization
      of the inner leaflet of human membrane.

PMID- 23010115
TI  - Dissolution process analysis using model-free Noyes-Whitney integral equation.
AB  - Drug dissolution process of solid dosages is theoretically described by Noyes
      Whitney-Nernst equation. However, the analysis of the process is demonstrated
      assuming some models. Normally, the model-dependent methods are idealized and
      require some limitations. In this study, Noyes-Whitney integral equation was
      proposed and applied to represent the drug dissolution profiles of a solid
      formulation via the non-linear least squares (NLLS) method. The integral equation
      is a model-free formula involving the dissolution rate constant as a parameter.
      In the present study, several solid formulations were prepared via changing the
      blending time of magnesium stearate (MgSt) with theophylline monohydrate, alpha
      lactose monohydrate, and crystalline cellulose. The formula could excellently
      represent the dissolution profile, and thereby the rate constant and specific
      surface area could be obtained by NLLS method. Since the long time blending
      coated the particle surface with MgSt, it was found that the water permeation was
      disturbed by its layer dissociating into disintegrant particles. In the end, the
      solid formulations were not disintegrated; however, the specific surface area
      gradually increased during the process of dissolution. The X-ray CT observation
      supported this result and demonstrated that the rough surface was dominant as
      compared to dissolution, and thus, specific surface area of the solid formulation
      gradually increased.

PMID- 23010116
TI  - Systematic investigation on the interaction of bovine serum albumin with ZnO
      nanoparticles using fluorescence spectroscopy.
AB  - Zinc oxide (ZnO) nanoparticles with average size of ~7.5nm were synthesized to
      investigate their interaction with bovine serum albumin (BSA) at different
      temperatures. Fluorescence quenching, synchronous and polarization spectroscopy
      along with UV-vis absorption, circular dichroism and resonance light scattering
      spectroscopy techniques were used to establish the interaction mechanism between
      ZnO and BSA. The obtained results confirmed that the ZnO nanoparticles (NPs)
      quench the fluorophore of BSA by forming ground state complex in the solution.
      The fluorescence quenching data was also used to determine binding sites and
      binding constants at different temperatures. The calculated thermodynamic
      parameters (DeltaG degrees , DeltaH degrees , and DeltaS degrees ) suggest that
      the binding process occurs spontaneously by involving hydrogen bond and van der
      Waals interactions. The synchronous fluorescence spectra reveal that the
      microenvironment close to both the tyrosine and tryptophan residues of BSA is
      perturbed and that the hydrophobicity of both the residues is increased in the
      presence of ZnO NPs. Resonance light scattering, circular dichroism, and
      fluorescence polarization spectra suggest the formation of BSA-ZnO complex and
      conformational changes in BSA. The calculated distance between the BSA and ZnO
      NPs suggests that the energy transfer from excited state of BSA to ZnO NPs occurs
      with high efficiency.

PMID- 23010117
TI  - Synthesis of Fe3O4@silica/poly(N-isopropylacrylamide) as a novel thermo
      responsive system for controlled release of H3PMo12O40 nano drug in AC magnetic
      field.
AB  - In this work, a new method is introduced for synthesis of nano drug for the first
      time. H(3)PMo(12)O(40) and Fe(3)O(4)@SiO(2)/poly(N-isopropylacrylamide), were
      prepared as nano drug and magneto thermally responsive nano-carrier respectively.
      Then the released behavior of H(3)PMo(12)O(40) nano-drug from this thermo
      responsive carrier was investigated in an AC magnetic field. When a drug particle
      is broken up to nanometer range, the total surface area is increased; therefore
      the rate of dissolution and the rate of release are increased. The as-synthesized
      nanostructures were characterized by scanning electron microscopy (SEM), X-ray
      powder diffraction (XRD), transmission electron microscopy (TEM), vibrating
      sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FT-IR).
      Furthermore, experimental condition which lead to the released profile of
      H(3)PMo(12)O(40) nano-drug from Fe(3)O(4)@SiO(2)/poly(N-isopropylacrylamide),
      such as strength of magnetic field (H), temperature (T), particle size of drug
      and content of loaded drug were tested. Increasing the strength of magnetic
      field, temperature and content of loaded drug, the rate of drug release was also
      increased.

PMID- 23010118
TI  - Antibacterial activities of Nd doped and Ag coated TiO2 nanoparticles under solar
      light irradiation.
AB  - Nanosized (8-9 nm) Nd doped and Ag coated TiO(2) nanoparticles have been
      synthesized by sol-gel method. The physicochemical properties of these particles
      were investigated by X-ray diffraction (XRD), diffuse reflectance UV-visible
      (DRUV) spectra and Brunauer-Emmett-Teller (BET) surface area analysis. The
      antibacterial activities of the samples were studied for Staphylococcus aureus
      (S. aureus) and Escherichia coli (E. coli) both, under the light and dark
      conditions. The results reveal that the extent of activity shows the order as
      undoped TiO(2)<Nd doped TiO(2)<Ag coated TiO(2). The mechanism of bactericidal
      action of the nanoparticles, in presence of sunlight has been explained with the
      help of microscopic analyses. The bacterial damage is observed to proceed through
      initial perforation of the cell, damage of cell wall and finally the bacterial
      death.

PMID- 23010119
TI  - Effect of Al2O3 nanoparticles on bacterial membrane amphiphilic biomolecules.
AB  - Lipopolysaccharide (LPS) and l-alpha-phosphatidyl-ethanolamine (PE) are
      amphiphilic biomolecules that are key constituents in the outer cell membranes of
      Gram-negative bacteria. In this study, micelles and vesicles of LPS/PE were used
      as cell membrane models to evaluate nanoparticle (NP) effects on membrane
      structure. Using atomic force microscopy and sorption experiments, we observed
      that LPS vesicles were dispersed by Al(2)O(3) NPs because of the strong
      attachment between LPS polysaccharide chain and oxide surface. LPS coated on the
      Al(2)O(3) NPs, and formed a layer of tens of nanometer as shown from atom force
      microscopy (AFM) images. High pH, ionic strength and sulfate concentration
      inhibited the adsorption of LPS molecules on NPs. The features of PE vesicles
      were changed after exposing to Al(2)O(3) NPs, inducing large round vesicles with
      detectable thickness as revealed by AFM, resulting in the increase of vesicle
      diameter. The aqueous stability of PE was disturbed when adding Al(2)O(3) NPs,
      but was enhanced by increasing pH. The interaction between NPs and membrane
      amphiphilic biomolecules may affect membrane fluidity, integrity and lateral
      organization, which is important for NP safety evaluation and for new NP designs
      in biological and biomedical applications.

PMID- 23010120
TI  - Tuning protein GlnB-Hs surface interaction with silicon: FTIR-ATR, AFM and XPS
      study.
AB  - Herbaspirillum seropedicae GlnB (GlnB-Hs) is a signal transduction protein
      involved in the control of nitrogen, carbon and energetic metabolism. The
      adsorption of GlnB-Hs deposited by spin coating on hydrophilic and hydrophobic
      silicon forms a thin layer that was characterized using atomic force microscopy
      (AFM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared
      attenuated total reflectance spectroscopy (FTIR-ATR). AFM allowed the
      identification of globular, face-up donut like array of protein on hydrophilic
      silicon substrate, favoring deprotonated residues to contact the silicon oxide
      surface. Over hydrophobic silicon, GlnB-Hs adopts a side-on conformation forming
      a filament network, avoiding the contact of protonated residues with silicon
      surface. XPS allowed us to determine the protonated and non-protonated states of
      nitrogen 1s (N 1s). The FTIR-ATR measurements provided information about protein
      secondary structure and its conservation, after surface adsorption.

PMID- 23010121
TI  - Bioremoval of Basic Violet 3 and Acid Blue 93 by Pseudomonas putida and its
      adsorption isotherms and kinetics.
AB  - Basic Violet 3 and Acid Blue 93 are the most important group of synthetic
      colourants extensively used in textile industries for dyeing cotton, wool, silk
      and nylon. Release of these dye pollutants in to the environment adversely
      affects the human health and aquatic organisms. The present study we used
      Pseudomonas putida MTCC 4910 for the adsorptive removal of Basic Violet 3 and
      Acid Blue 93 from the aqueous solutions. The pH (4-9) and NaCl concentrations
      (1mM-1M) did not influence the adsorption process. The equilibrium adsorption
      process fitted well to Freundlich model than Langmuir model. The kinetics of
      adsorption fitted well by pseudo-second-order. Thus in the present study an
      attempt has been made to exploit the dye removal capability of P. putida MTCC
      4910, and it was found to be an efficient microbe that could be used for bio
      removal of dyes from textile effluents.

PMID- 23010122
TI  - New voltammetric strategy for simultaneous determination of N-acetylcysteine and
      folic acid using a carbon nanotube modified glassy carbon electrode.
AB  - A novel 1-benzyl-4-ferrocenyl-1H-[1,2,3]-triazole (BFT)/carbon nanotube modified
      glassy carbon electrode (BFT-CNT-GCE) was prepared for the simultaneous
      determination of N-acetylcysteine (NAC) and folic acid (FA). Cyclic voltammetry
      (CV), chronoamperometry (CHA), and square wave voltammetry (SWV) methods were
      used to investigate the modified electrode for the electrocatalytic oxidation of
      NAC and FA in aqueous solutions. The separation of the oxidation peak potentials
      for NAC-FA was about 280 mV. The calibration curve obtained for NAC was in the
      range of 0.1-600.0 MUM. The detection limit (S/N=3) was 62.0+/-2.0 nM for NAC.
      The diffusion coefficient and the catalytic rate constant for the oxidation of
      NAC at the modified electrode were calculated as (3.5+/-0.2)*10(-5) cm(2) s(-1)
      and (9.85+/-0.4)*10(-4) M(-1) s(-1), respectively. The method was employed for
      the determination of NAC and FA in some real samples.

PMID- 23010123
TI  - Solid lipid nanoparticles as delivery systems for Gambogenic acid.
AB  - In this study, Gambogenic acid loaded by solid lipid nanoparticles (GNA-SLNs) was
      explored to reduce toxicity and improve therapeutic efficacy. GNA-SLNs were
      prepared by emulsification and low temperature solidification methods, and the
      freeze-dried powders were then developed to improve the stability. The physical
      chemical properties of the products in terms of particle size, zeta potential,
      morphology and entrapment efficiency were well evaluated. The results revealed
      that the mean diameter, polydispersivity index (PI), zeta potential, and the
      entrapment efficiency of the nanoparticles were 163.3 nm, 0.203, -16.9 mV and
      61.2%, respectively. In comparion with GNA-SLNs, the freeze-dried solid lipid
      nanoparticles (SLNs) showed a slight augmentation in the mean particle size (from
      163.3 to 173 nm) and PI (from 0.203 to 0.253), and no significant modification in
      the zeta potential, entrapment efficiency and drug loading. In vitro release
      kinetics based on a dialysis method demonstrated that Gambogenic acid (GNA) was
      released in a prolonged fashion for 96 h and followed Higuchi equation unitarily.
      The release profile did not show any significant modification after the freeze
      drying process. The Pharmacokinetic study was carried out, the i.p.
      administration of GNA formulations to rats at doses of 2.5mg/kg. AUC((0-t)) was
      increased (up to 3.1-fold) and clearance was decreased (up to 3.03-fold) when GNA
      entrapped in SLNs. In conclusions, the freeze-dried powders form could enhance
      the long-term stability of SLN, and solid lipid nanoparticles encapsulation could
      effectively strategy to change the poor aqueous solubility and prolong the half
      life of GNA.

PMID- 23010124
TI  - Differentiation of induced pluripotent stem cells toward neurons in hydrogel
      biomaterials.
AB  - Regeneration of nerve tissue is one of the most significant challenges in
      contemporary surgical therapy for nervous system injury. This study presents the
      neuronal differentiation of induced pluripotent stem (iPS) cells in hydrogels
      comprising alginate and poly(gamma-glutamic acid) (gamma-PGA) with surface neuron
      growth factor (NGF). Differentiating iPS cells in NGF-grafted alginate/gamma-PGA
      constructs were identified by immunochemical staining of anti-SSEA-1 and anti
      beta III tubulin. The results revealed that the pore diameter of hydrogels
      increased with an increasing weight ratio of alginate to gamma-PGA. The porosity
      slightly decreased with an increasing weight ratio of alginate to hydrogel. In
      addition, an increase in the weight ratio of alginate to hydrogel raised the
      swelling ratio. Morphological images of differentiating iPS cells in NGF-grafted
      alginate/gamma-PGA constructs exhibited neuronal characteristics. The surface NGF
      enhanced the intensity of beta III tubulin and inhibited the intensity of SSEA-1
      expressed by differentiating iPS cells in cultured constructs, indicating the
      differentiation of iPS cells toward neurons. NGF-grafted alginate/gamma-PGA
      hydrogels can be efficient biomaterials in the production of neurons from iPS
      cells for animal study and preclinical trial.

PMID- 23010125
TI  - Non-cytotoxic antibacterial silver-coumarin complex doped sol-gel coatings.
AB  - Microbial colonisation on clinical and industrial surfaces is currently of global
      concern and silane based sol-gel coatings are being proposed as potential
      solutions. Sol-gels are chemically inert, stable and homogeneous and can be
      designed to act as a reservoir for releasing antimicrobial agents over extended
      time periods. In the present study, silver nitrate (AgN) and a series of silver
      coumarin complexes based on coumarin-3-carboxylatosilver (AgC) and it is 6, 7 and
      8 hydroxylated analogues (Ag6, Ag7, Ag8) were incorporated into sol-gel coatings.
      The comparative antibacterial activity of the coatings was determined against
      meticillin resistant Staphylococcus aureus (MRSA) and multidrug resistance
      Enterobacter cloacae WT6. The percentage growth inhibitions were found in the
      range of 9.2 (+/-2.7)-66.0 (+/-1.2)% at low silver loadings of 0.3% (w/w) with E.
      cloacae being the more susceptible. Results showed that among the Ag coumarin
      complexes, the Ag8 doped coating had the highest antibiofilm property. XPS
      confirmed the presence of silver in the nanoparticulate state (Ag(0)) at the
      coating surface where it remained after 4 days of exposure to bacterial culture.
      Comparative cytotoxicity studies revealed that the Ag-complex coatings were less
      toxic than the AgN coating. Thus, it can be concluded that a sol-gel matrix with
      Ag-coumarin complexes may provide non-toxic surfaces with antibacterial
      properties.

PMID- 23010126
TI  - Magnetite nanoparticles doped photoresist derived carbon as a suitable substratum
      for nerve cell culture.
AB  - A method which alters the substrate's physical and electrochemical properties by
      doping photoresist derived carbon with magnetite nanoparticles has been developed
      to enhance the existing substrate's ability to foster cell growth. Cyclic
      voltammetry, scanning electron microscopy and atomic force microscopy are used to
      evaluate the characters of the prepared film. And then, the magnetite
      nanoparticles doped carbon film is used as substrate for the growth of nerve
      cell. Here, rat pheochromocytoma cells are used for culture to test substrate
      cell interactions. The results showed an increase in cell concentration and
      average neurite length with the increase of nanoparticle concentration on the
      surface. Importantly, the nerve cells can be grown on the magnetite nanoparticles
      doped carbon even in the absence of nerve growth factor. This finding will
      potentially provide a new material for nerve regeneration.

PMID- 23010127
TI  - The adsorption mechanism of titanium-binding ferritin to amphoteric oxide.
AB  - We investigated the origin of selective adsorption of titanium-binding ferritin
      (TBF), the outer surface of which is genetically modified with titanium-binding
      peptides (TBPs). By varying pH conditions (7-9), TBF adsorption behavior onto
      amphoteric and acidic oxide substrates was observed using atomic force
      microscopy, and the zeta potential of substrates was measured. This suggests that
      a TBP interacted with local charges such as -O(-), -OH(+), and -OH(2)(+) on
      substrates regardless of the constituent elements of the substrate, which makes
      it possible for TBF to adsorb on TiO(X), ZrO(2), Fe(2)O(3), and SiO(2) substrates
      despite the presence of an overall electrostatic repulsive force between TBF and
      the substrates. This also suggests that a surfactant, TWEEN20, can completely
      hamper attractive interaction between TBF and acidic oxide, but amphoteric oxide
      can withstand TWEEN20 interference.

PMID- 23010128
TI  - Poly(epsilon-caprolactone), Eudragit(r) RS 100 and poly(epsilon
      caprolactone)/Eudragit(r) RS 100 blend submicron particles for the sustained
      release of the antiretroviral efavirenz.
AB  - The design of simple and scalable drug delivery systems to target the central
      nervous system (CNS) could represent a breakthrough in the addressment of the HIV
      associated neuropathogenesis. The intranasal (i.n.) route represents a minimally
      invasive strategy to surpass the blood-brain barrier, though it demands the use
      of appropriate nanocarriers bearing high drug payloads and displaying
      sufficiently long residence time. The present work explored the development of
      submicron particles made of poly(epsilon-caprolactone) (PCL), Eudragit((r)) RS
      100 (RS a copolymer of ethylacrylate, methylmethacrylate and methacrylic acid
      esterified with quaternary ammonium groups) and their blends, loaded with the
      first-choice antiretroviral efavirenz (EFV) as an approach to fine tune the
      particle size and the release kinetics. Particles displaying hydrodynamic
      diameters between 90 and 530 nm were obtained by two methods: nanoprecipitation
      and emulsion/solvent diffusion/evaporation. In general, the former resulted in
      smaller particles and narrower size distributions. The encapsulation efficiency
      was greater than 94%, the drug weight content approximately 10% and the yield in
      the 72.5-90.0% range. The highly positive surface (>+30 mV) rendered the
      suspensions physically stable for more than one month. In vitro release assays
      indicated that the incorporation of the poly(methacrylate) into the composition
      reduced the burst effect and slowed the release rate down with respect to pure
      poly(epsilon-caprolactone) particles. The analysis of the release profile
      indicated that, in all cases, the kinetics adjusted well to the Higuchi model
      with R(adj)(2) values >0.9779. These findings suggested that the release was
      mainly controlled by diffusion. In addition, when data were analyzed by the
      Korsmeyer-Peppas model, n values were in the 0.520-0.587 range, indicating that
      the drug release was accomplished by the combination of two phenomena: diffusion
      and polymer chain relaxation. Based on ATR/FT-IR analysis that investigated
      drug/polymer matrix interactions, the potential role of the hydrophobic
      interactions of C-F groups of EFV with carbonyl groups in the backbone of PCL and
      poly(methacrylate) could be ruled out. The developed EFV-loaded particles appear
      as a useful platform to investigate the intranasal administration to increase the
      bioavailability in the CNS.

PMID- 23010129
TI  - Isolation and immobilization of aroid polyphenol on magnetic nanoparticles:
      enhancement of potency on surface immobilization.
AB  - Five polyphenolic compounds were isolated from four aroid species [using High
      Performance Liquid Chromatography (HPLC)] and identified using Fourier Transform
      Infrared (FTIR) spectroscopy and Nuclear Magnetic Resonance (NMR) analysis. The
      compounds benzoic acid, caffeic acid, coumaric acid, ferulic acid and syringic
      acids were immobilized on magnetic nanoparticles (MNPs) using poly(ethylene
      glycol) (PEG) as linker polymer. The obtained PEG-MNP-polyphenol trios were
      characterized using transmission electron microscopy (TEM) and FTIR. Their
      biochemical characterization were done to find out the DPPH scavenging capacity
      and amount of polyphenol loaded (galic acid equivalent) in each type of MNP
      polyphenol trio. To know the antioxidant activity the MNP-polyphenol trios were
      subjected to H(2)O(2) induced haemolysis prevention assay and syringic acid trio
      was found to most potent. To ensure that the MNP-polyphenol trios were
      magnetically active the hysteresis loop analysis was also done.

PMID- 23010130
TI  - Fabrication of biomolecule-PEG micropattern on titanium surface and its effects
      on platelet adhesion.
AB  - Reducing platelet adhesion, controlling platelet distribution and decreasing
      degree of platelet activation are very important for improving blood
      compatibility of cardiovascular implants. In this study, the micropattern of
      heparin and fibronectin mixture (Hep-Fn) embedded within a cell-resistant alpha
      methoxy-poly(ethylene glycol)-omega-succinimidyl carbonate (mPEG-SC) background
      was fabricated on titanium (Ti) surface. Firstly, the Ti sample was activated by
      NaOH solution and treated with ethanol solution of (3-aminopropyl)
      triethoxysilane (APTE). Secondly, microtransfer molding (MUTM) was used to
      pattern mPEG-SC for resisting protein absorption and platelet adhesion on
      silanized Ti surface. Finally, Hep-Fn mixture was absorbed on the areas uncovered
      by mPEG-SC to form a surface for selective adhesion of platelet. Scanning
      electron microscopy (SEM) showed the surface morphology of the patterned Ti,
      Fourier transform infrared spectroscopy (FTIR) demonstrated the existence of Hep
      Fn and mPEG-SC on the modified Ti surface. The platelet adhesion test was used to
      evaluate adhesion, activation and distribution of platelets on the bare Ti
      samples with or without biomolecule micropattern. The results indicated that the
      patterned samples could effectively reduce platelet adhesion, control platelet
      distribution and influence platelet activation compared with the non-patterned
      pure Ti sample. The micropattern sample, P25/10 with a geometry of 25 MUm mPEG-SC
      (ridges) and 10 MUm Hep-Fn (grooves), presented better blood compatibility.

PMID- 23010131
TI  - Congenital and oral transmission of American trypanosomiasis: an overview of
      physiopathogenic aspects.
AB  - Chagas disease or American trypanosomiasis is a pathology affecting about 8-11
      million people in Mexico, Central America, and South America, more than 300 000
      persons in the United States as well as an indeterminate number of people in
      other non-endemic countries such as USA, Spain, Canada and Switzerland. The
      aetiological agent is Trypanosoma cruzi, a protozoan transmitted by multiple
      routes; among them, congenital route emerges as one of the most important
      mechanisms of spreading Chagas disease worldwide even in non-endemic countries
      and the oral route as the responsible of multiple outbreaks of acute Chagas
      disease in regions where the vectorial route has been interrupted. The aim of
      this review is to illustrate the recent research and advances in host-pathogen
      interaction making a model of how the virulence factors of the parasite would
      interact with the physiology and immune system components of the placental
      barrier and gastrointestinal tract in order to establish a response against T.
      cruzi infection. This review also presents the epidemiological, clinical and
      diagnostic features of congenital and oral Chagas disease in order to update the
      reader about the emerging scenarios of Chagas disease transmission.

PMID- 23010132
TI  - Factors associated with intended and effective settlement of nursing students and
      newly graduated nurses in a rural setting after graduation: a mixed-methods
      review.
AB  - OBJECTIVES: To identify factors that influence the initial plan and final
      decision to choose a rural area as first employment location in final-year
      nursing students or newly graduated nurses. DESIGN: We conducted a mixed-methods
      review of the literature, including both published and gray literature, using
      established criteria. Two reviewers performed data extraction of relevant
      information independently. DATA SOURCES: We retrieved empirical studies from the
      following databases: PubMED, Embase, CINAHL (EBSCO), Web of Science (SCI and
      SSCI), The Cochrane Library, Business Source Premier (EBSCO), ERIC, Proquest and
      PsychInfo. We also searched for empirical studies in the technical and gray
      literature and reviewed journals related to rural health. Additionally, we
      conducted searches in websites such as the Center for Health Workforce Planning
      and Analysis, as well as Google and Google Scholar search engines. RESULTS: Of
      the 523 studies thus screened, 15 were included for data extraction. We
      identified more than 40 factors associated with initial plans and final decision
      to settle in a rural area among nursing graduates. CONCLUSIONS: Only limited
      literature is currently available on the factors associated with the intention of
      nursing students or newly graduated nurses of practicing in rural areas and on
      the relationship between intention and effective behavior. This review highlights
      the needs for further research in this field.

PMID- 23010133
TI  - Publication efficiency among the higher impact factor nursing journals in 2009: a
      retrospective analysis.
AB  - BACKGROUND: Knowledge translation is attracting different professional,
      educational and institutional strategies mainly focused on how new knowledge
      should be tailored and transferred at bedside. Less attention is dedicated to the
      antecedent of knowledge translation, which is the availability of the knowledge
      itself. Knowledge diffusion is a process by which an innovation is communicated
      through certain channels among members of a social system over time. Publishing
      in peer review journals is recognised as the main method for knowledge diffusion:
      nevertheless publication efficiency has received little attention to date.
      OBJECTIVES: Describing publication efficiency via nursing journals as the time
      occurring between data collection and manuscript publication was the main aim of
      the study. The secondary aim was to discover the differences, if any, in
      publication efficiency within manuscripts reporting results from different study
      designs. DESIGN: A retrospective study design was adopted in 2010. METHODS: The
      2009 Impact Factor List of Nursing Journals published by the ISI web of Knowledge
      in 2010 was obtained. The first top ten IF Nursing Journals available as a full
      text and for which the overall ISI 5-Year Impact Factor was also available, was
      eligible. The articles published on paper by the selected journals, from 1st
      January to 31st December 2009, were then included. Commentaries, editorials and
      book reviews were excluded. For each article included, the following were
      evaluated: (a) the time occurring between each step of publication, from data
      collection to article submission, acceptance and publication online and on paper;
      and (b) the differences in the publication efficiency within articles reporting
      different study designs. RESULTS: 1152 articles were included. From the end of
      data collection to manuscript publication online/on paper it takes an average of
      981 days [CI95% 929-1032] (2.5-3 years). Meta-analysis and systematic reviews
      have demonstrated the fastest process, requiring an average 1.3 years and 1.9
      years respectively. Case-control, cohort and quasi-experimental studies have
      required more time to enjoy publication in nursing journals, 4 years, 3.5 years
      and 3.2 years respectively. CONCLUSIONS: The production time of an article from
      its data collection involves significant processes and skills. However, the time
      may also be lengthened by factors not related to the processes of research, such
      as the time available to researchers. The scientific world needs to reflect on
      publication efficiency because lateness can potentially have a negative impact on
      patients and on further research. In the future, the same emphasis given to the
      evaluation of knowledge translation effectiveness should be given also to the
      complex process of knowledge diffusion, discovering facilitators and barriers.

PMID- 23010135
TI  - Continuous buccolingual masticatory dyskinesia in Parkinson's disease.
AB  - Usually, levodopa-induced dyskinesia does not remain unchanged throughout the day
      in Parkinson's disease (PD) patients and varies according to the level of
      correction of PD symptomatology provided by the treatment. We observed two PD
      patients with unusual buccolingual masticatory movements which did not seem to
      fluctuate, either throughout the day during dopaminergic treatment or during a
      standardised levodopa challenge. After their dopaminergic treatment had been
      changed to a less pulsatile form of administration (ie, the use of dopamine
      agonist alone in the first patient and an increase in the dosage of dopamine
      agonist with a low dose of levodopa in the second), these abnormal movements
      totally disappeared in the first patient and were greatly improved in the second.
      These observations suggest that levodopa can have prolonged effects (several
      days) and induce prolonged buccolingual masticatory movements similar in type to
      those classically observed with dopamine receptor antagonists (neuroleptics).

PMID- 23010134
TI  - Development and preliminary testing of a brief screening measure of healthy
      lifestyle for diabetes patients.
AB  - OBJECTIVES: Improving diabetes control is a critical issue world-wide, because
      mortality rates and costs are increasing dramatically. Maintaining a healthy
      lifestyle is positively associated with diabetes control. However, the
      availability of practical screening tools suitable for determining and modifying
      healthy or unhealthy lifestyle choices is limited. The main aim of this study was
      to determine the appropriateness of the type 2 diabetes and health promotion
      scale (T2DHPS) for use in patients with type 2 diabetes. METHODS: This study
      examined the Cronbach's alpha, content validity, construct and concurrent
      validity of the Chinese language version of the T2DHPS for assessing lifestyle
      and disease control among patients with type 2 diabetes. The dimensions of the
      T2DHPS were generated from the Chinese version of adult health promotion and
      interviews with experts, and were corroborated by the literature. A total of 323
      patients previously diagnosed with type 2 diabetes were recruited. A cross
      sectional, descriptive design questionnaire was developed and tested at diabetes
      outpatient departments in three teaching hospitals between August 2010 and June
      2011. Construct validity was established using factor analysis. The total and
      subscale scores of the T2DHPS were correlated with biomarkers of diabetes control
      for concurrent validity. RESULTS: Kaiser-Meyer-Olkin (KMO) and Bartlett's
      sphericity tests showed that the sample met the criteria required for factor
      analysis. A 28-item Likert-type scale of the T2DHPS was established, and
      explained 56.7% of the total variance. The simplified version of the T2DHPS was
      made up of six dimensions of behavior: physical activity, risk reduction, stress
      management, enjoy life, health responsibility and a healthy diet. The reliability
      coefficient for the total scale was 0.89, and alpha coefficients for the
      subscales ranged from 0.63 to 0.86. Concurrent validity indicated that the T2DHPS
      is significantly positively associated with diabetes control. CONCLUSIONS: T2DHPS
      was shown to be a reliable and valid tool for assessing patients with type 2
      diabetes, and can possibly predict diabetic control. This scale appears to be a
      useful screening tool for type 2 diabetic people in primary health care settings,
      to promote health status through modification of an unhealthy lifestyle.

PMID- 23010136
TI  - A role for hippocampal actin rearrangement in object placement memory in female
      rats.
AB  - Actin rearrangement, the polymerization of globular actin (G-actin) to
      filamentous actin, causes morphological changes in dendritic spines and is
      hypothesized to be a substrate of learning and memory. The ovarian hormone
      estradiol promotes hippocampal actin rearrangement and enhances performance on
      hippocampus-dependent tasks, including object placement memory. The goals of the
      current study were to determine a role for actin rearrangement and its regulatory
      pathway in object placement memory in female rats and to determine if estradiol
      impacts actin rearrangement in ovariectomized rats during the performance of the
      task. In an initial experiment, young adult Long-Evans rats were ovariectomized
      and implanted with capsules containing either cholesterol vehicle or estradiol.
      Bilateral intrahippocampal infusions of aCSF vehicle or the actin rearrangement
      inhibitor, latrunculin A, were administered 15 min prior to initiation of the
      object placement task. Latrunculin A dose-dependently impaired object placement
      memory. Estradiol had no impact on the ability of latrunculin A to affect
      performance. In a second experiment, rats were ovariectomized and received
      implants containing cholesterol or estradiol. Half of each hormone treatment
      group was exposed to the object placement memory task and half underwent control
      procedures. Immediately following completion of behavior, rats were euthanized
      and hippocampi removed. Western blotting was used to measure hippocampal levels
      of phosphorylated and total levels of a regulator of actin polymerization, the
      actin depolymerization factor cofilin. Exposure to the object placement memory
      task resulted in significant increases in phosphorylated levels of cofilin.
      Estradiol treatment had no impact on protein levels. These data support a role
      for hippocampal actin rearrangement and its regulatory proteins in object
      placement memory in female rats and suggest that chronic estradiol treatment does
      not impact hippocampal actin arrangement.

PMID- 23010137
TI  - Baclofen administration alters fear extinction and GABAergic protein levels.
AB  - The investigation of GABAergic systems in learning and extinction has principally
      focused on ionotropic GABA(A) receptors. Less well characterized is the
      metabotropic GABA(B) receptor, which when activated, induces a more sustained
      inhibitory effect and has been implicated in regulating oscillatory activity. Few
      studies have been carried out utilizing GABA(B) ligands in learning, and
      investigations of GABA(B) in extinction have primarily focused on interactions
      with drugs of abuse. The current study examined changes in GABA(B) receptor
      function using the GABA(B) agonist baclofen (2 mg/mL) or the GABA(B) antagonist
      phaclofen (0.3 mg/mL) on trace cued and contextual fear conditioning and
      extinction. The compounds were either administered during training and throughout
      extinction in Experiment 1, or starting 24 h after training and throughout
      extinction in Experiment 2. All drugs were administered 1 mL/kg via
      intraperitoneal injection. These studies demonstrated that the administration of
      baclofen during training and extinction trials impaired animals' ability to
      extinguish the fear association to the CS, whereas the animals that were
      administered baclofen starting 24 h after training (Experiment 2) did display
      some extinction. Further, contextual fear extinction was impaired by baclofen in
      both experiments. Tissue analyses suggest the cued fear extinction deficit may be
      related to changes in the GABA(B2) receptor subunit in the amygdala. The data in
      the present investigation demonstrate that GABA(B) receptors play an important
      role in trace cued and contextual fear extinction, and may function differently
      than GABA(A) receptors in learning, memory, and extinction.

PMID- 23010139
TI  - [The impact of direct access to primary angioplasty on reducing the mortality
      associated with anterior ST-segment elevation myocardial infarction: the
      experience of the Algarve region of Portugal].
AB  - INTRODUCTION: There are few published data on mortality in anterior ST-segment
      elevation myocardial infarction (STEMI) in Portugal, particularly in centers with
      direct access to primary angioplasty. We present the experience of a center with
      direct access to primary angioplasty in the management of patients admitted with
      anterior STEMI. METHODS: We performed a retrospective study of 120 patients
      admitted with anterior STEMI in 2008 to Faro Hospital (Algarve region, Portugal).
      RESULTS: Significant coronary artery stenosis was found in 99 patients (82.5%).
      These patients were predominantly male (79%), and had a mean age of 63 years.
      Primary angioplasty was performed in the majority of patients within 6 hours of
      symptom onset and median ECG-to-balloon time was 89 minutes. Primary angioplasty
      was successful in 98% of patients and complete revascularization was achieved in
      83%. Radial access was used in 82% of cases. In-hospital and 30-day mortality was
      3%. CONCLUSION: Direct access to primary angioplasty was associated with low
      mortality in patients admitted with anterior STEMI.

PMID- 23010138
TI  - Skill learning induced plasticity of motor cortical representations is time and
      age-dependent.
AB  - Movement representations in the motor cortex can reorganize to support motor
      skill learning during young adulthood. However, little is known about how motor
      representations change during aging or whether their change is influenced by
      continued practice of a skill after it is learned. We used intracortical
      microstimulation to characterize the organization of the forelimb motor cortex in
      young and aged C57/BL6 mice after short (2-4 weeks) or long (8 weeks) durations
      of training on a skilled reaching task or control procedures. In young mice, a
      short duration of reach training increased the area of proximal forelimb movement
      representations at the expense of distal representations. Following a longer
      training duration, ratios of proximal to distal movements returned to baseline,
      even with ongoing practice and skill maintenance. However, lingering changes were
      evident in thresholds for eliciting distal forelimb movements, which declined
      over the longer training period. In aged mice, movement representations and
      movement thresholds failed to change after either duration of training.
      Furthermore, there was an age-related loss of digit representations and
      performance decrements on other sensorimotor tests. Nevertheless, in quantitative
      measures of reaching success, aged mice learned and performed the skilled
      reaching task at least as well as younger mice. These results indicate that
      experience-driven topographical reorganization of motor cortex varies with age,
      as well as time, and is partially dissociable from behavioral performance. They
      also support an enduring capacity to learn new manual skills during aging, even
      as more youthful forms of cortical plasticity and sensorimotor function are lost.

PMID- 23010140
TI  - Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles:
      proteoliposomes as a tool to gain insights in the molecular mechanism of action
      and of antitumor activity.
AB  - The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and
      other neutral amino acids which is involved in amino acid metabolism. A library
      of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the
      glutamine/amino acid ASCT2 transporter in the model system of proteoliposomes
      reconstituted with the rat liver transporter. Fifteen of the tested compounds at
      concentration of 20MUM or below, inhibited more than 50% the glutamine/glutamine
      antiport catalysed by the reconstituted transporter. These good inhibitors bear a
      phenyl ring with electron withdrawing substituents. The inhibition was reversed
      by 1,4-dithioerythritol indicating that the effect was likely owed to the
      formation of mixed sulfides with the protein's Cys residue(s). A dose-response
      analysis of the most active compounds gave IC(50) values in the range of 3-30MUM.
      Kinetic inhibition studies indicated a non-competitive inhibition, presumably
      because of a potential covalent interaction of the dithiazoles with cysteine
      thiol groups that are not located at the substrate binding site. Indeed,
      computational studies using a homology structural model of ASCT2 transporter,
      suggested as possible binding targets, Cys-207 or Cys-210, that belong to the
      CXXC motif of the protein.

PMID- 23010142
TI  - Adolescence fluoxetine increases serotonergic activity in the raphe-hippocampus
      axis and improves depression-like behaviors in female rats that experienced
      neonatal maternal separation.
AB  - This study was conducted to examine if fluoxetine, a selective 5
      hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral
      effects of neonatal maternal separation in female rats. Sprague-Dawley pups were
      separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal
      separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups
      received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from
      PND 35 until the end of the whole experimental period. Rats were either subjected
      to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses
      during PND 43-45. Daily food intake and weight gain of both NH and MS pups were
      suppressed by fluoxetine, with greater effects in MS pups. MS experience
      increased immobility and decrease swimming in forced swim test. Swimming was
      increased, although immobility was not significantly decreased, in MS females by
      adolescence fluoxetine. However, adolescence fluoxetine increased immobility
      during forced swim test and decreased time spent in open arms during elevated
      plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the
      raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females,
      and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the
      raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest
      that decreased 5-HTergic activity in the raphe nucleus is implicated in the
      pathophysiology of depression-like behaviors, and increased 5-HTergic activities
      in the raphe-hippocampus axis may be a part of anti-depressant efficacy of
      fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may
      contribute to the increased anorectic efficacy of fluoxetine in MS females.
      Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may
      be related with fluoxetine-induced depression- and/or anxiety-like behaviors in
      NH females.

PMID- 23010141
TI  - Many roads lead to recognition: electrophysiological correlates of familiarity
      derived from short-term masked repetition priming.
AB  - The neural mechanisms that underlie familiarity memory have been extensively
      investigated, but a consensus understanding remains elusive. Behavioral evidence
      suggests that familiarity sometimes shares sources with instances of implicit
      memory known as priming, in that the same increases in processing fluency that
      give rise to priming can engender familiarity. One underappreciated implication
      of this account is that patterns of neural activity that appear to index
      familiarity in a generic sense may instead reflect fluency-related precursors of
      recognition. In a novel illustration of this principle, we examined brain
      potentials during recognition tests for visual words. In two experiments, fluency
      was selectively enhanced for half of the test cues via masked repetition priming.
      Replicating previous findings, the proportion of words endorsed as "old" was
      greater for words immediately preceded by a matching masked word versus an
      unrelated one. In addition, N400 potentials were more positive for test cues
      preceded by matching versus unrelated masked words. Similar N400 differences were
      observed when false alarms were compared to correct rejections for the subset of
      unstudied words that were preceded by matching masked words. These N400 effects
      were topographically dissociable from other potentials that correlated with
      familiarity for studied words. We conclude that experiences of familiarity can
      have different neural correlates that signal the operation of distinct
      neurocognitive precursors of recognition judgments. Conceptualizations of the
      neural basis of recognition memory must account for a plurality of mechanisms
      that produce familiarity memory.

PMID- 23010144
TI  - Ocular Surface Disease Index (OSDI): a potential useful instrument for the
      assessment of vision-targeted health-related quality of life (VT-HRQ) in primary
      Sjogren's syndrome (pSS) clinical trials?

PMID- 23010143
TI  - Distinguishing features of cancer patients who smoke: pain, symptom burden, and
      risk for opioid misuse.
AB  - Although many cancer patients who have pain are smokers, the extent of their
      symptom burden and risk for opioid misuse are not well understood. In this study
      we analyzed records of patients being treated for cancer pain, 94 of whom were
      smokers and 392 of whom were nonsmokers, to determine smoking status group
      differences. Smokers had significantly higher pain intensity, fatigue,
      depression, and anxiety than nonsmokers (independent samples t-tests P < .002).
      Smokers were at higher risk for opioid misuse based on the short form of the
      Screener and Opioid Assessment for Patients with Pain (SOAPP). Specifically,
      smokers had more frequent problems with mood swings, taking medications other
      than how they are prescribed, a history of illegal drug use, and a history of
      legal problems (chi-square tests P <= .002). Changes in pain and opioid use were
      examined in a subset of patients (146 nonsmokers and 46 smokers) who were
      receiving opioid therapy on at least 2 of the 3 data time points (consult, follow
      up 1 month after consult, follow-up 6 to 9 months after consult). Results based
      on multilevel linear modeling showed that over a period of approximately 6
      months, smokers continued to report significantly higher pain than nonsmokers.
      Both smokers and nonsmokers reported a significant decline in pain across the 6
      month period; the rate of decline did not differ across smokers and nonsmokers.
      No significant difference over time was found in opioid use between smokers and
      nonsmokers. These findings will guide subsequent studies and inform clinical
      practice, particularly the relevancy of smoking cessation. PERSPECTIVE: This
      article describes pain, symptom burden, and risk for opioid misuse among cancer
      patients with pain across smoking status. Smoking appears to be a potential
      mechanism for having an increased pain and symptom burden and risk for opioid
      misuse. This improved understanding of cancer pain will inform clinical practice.

PMID- 23010145
TI  - A brief overview of space applications for ultrasonics.
AB  - Sonics and space are two topics which are not commonly considered together.
      However, sonic and ultrasonic models, devices and systems have space applications
      in both science and engineering, as well as showing promise in fields such as
      cleaning, healthcare and construction. This short paper describes some of these
      activities and appears as results start to come in from the Curiosity rover,
      which landed on Mars on the 6th of August, 2012, with over 20 piezoelectric and
      mechanically-resonant components on board.

PMID- 23010146
TI  - Lower carotid intima media thickness is predicted by higher serum bilirubin in
      both non-diabetic and Type 2 diabetic subjects.
AB  - BACKGROUND: Higher serum bilirubin levels may be implicated cardiovascular
      protection. It is unknown whether the impact of serum bilirubin on carotid artery
      intima media thickness (IMT), a marker of subclinical atherosclerosis, is
      different in diabetic subjects compared to non-diabetic subjects. We assessed
      relationships of IMT with serum total bilirubin in non-diabetic and Type 2
      diabetic subjects without clinically manifest cardiovascular disease. METHODS:
      IMT, total bilirubin, transaminases, C-reactive protein (CRP) and lipid levels
      were measured in 40 predominantly middle-aged non-diabetic and 80 diabetic
      subjects. RESULTS: IMT was higher in diabetic subjects compared to non-diabetic
      subjects (unadjusted, p<0.001), whereas bilirubin was not different (p=0.82). In
      both non-diabetic and in diabetic subjects, IMT was negatively related to
      bilirubin (beta=-0.316, p=0.045 and beta=-0.247 p=0.014, respectively) taking
      account of age, sex and mean arterial pressure. In the combined subjects, IMT
      remained independently related to bilirubin (beta=-0.183, p=0.028) after
      additional adjustment for diabetes status, alcohol intake, transaminases, CRP and
      lipid levels. There was no interaction of bilirubin with the presence of diabetes
      on IMT (p=0.98). CONCLUSION: Carotid artery IMT relates negatively to bilirubin
      in non-diabetic and Type 2 diabetic subjects. The association of subclinical
      atherosclerosis with bilirubin appears to be unaltered in the diabetic state.

PMID- 23010147
TI  - Indications for bone marrow examination in autoimmune disorders with concurrent
      haematologic alterations.
AB  - OBJECTIVES: The aim of this study was to evaluate the aetiology of 'unexplained'
      cytopenias in patients with autoimmune disorders, as well as to identify
      parameters that should alert clinicians to the need for bone marrow examination.
      METHODS: During the study period (2005-2010), 110 consecutive patients with an
      underlying systemic autoimmune disease, excluding Sjogren's syndrome, were
      referred for haematological consultation and bone marrow examination, due to
      cytopenias without evident cause including blood loss, haemolysis, nutritional
      deficiencies and haemoglobin disorders. RESULTS: Systemic lupus erythaematosus
      was the most frequent underlying condition (38/110, 34.5%), and anaemia
      (haemoglobin<12gr/dl) the most common haematologic abnormality (81/110, 74%).
      Prior to evaluation, more than half of the patients received cytotoxic or
      immunosuppressive drugs, with methotrexate being the most commonly administrated
      agent (29/110, 26.4%). Evaluation was informative in 31 (28.2%) of the cases.
      Twenty-four (21.8%) cases of haematologic clonal disease were diagnosed; 11
      myelodysplastic syndromes, 6 lymphoproliferative disorders, 6 plasma cell
      dyscrasias and one myeloproliferative neoplasm. Seven cases (6.4%) with bone
      marrow toxicity were also noted. Male gender, serum iron >90 MUg/dl, mean
      corpuscular volume (MCV) >90fl, and serum monoclonal band were significant
      predictors of specific diagnosis including clonal haematologic disorder or bone
      marrow toxicity. All other correlations were insignificant. CONCLUSIONS: Clonal
      haematologic disorders and toxicity are frequent findings in patients with
      autoimmunity referred for haematologic consultation, owing to otherwise
      unexplained cytopenias. Patients with high serum iron, high MCV and presence of
      serum monoclonal band should undergo bone marrow examination to exclude
      haematologic malignancy or bone marrow toxicity.

PMID- 23010148
TI  - Epidemiological features and risk factors of Salmonella gastroenteritis in
      children resident in Ho Chi Minh City, Vietnam.
AB  - Non-typhoidal Salmonella are an important but poorly characterized cause of
      paediatric diarrhoea in developing countries. We conducted a hospital-based case
      control study in children aged <5 years in Ho Chi Minh City to define the
      epidemiology and examine risk factors associated with Salmonella diarrhoeal
      infections. From 1419 diarrhoea cases and 571 controls enrolled between 2009 and
      2010, 77 (5?4%) diarrhoea cases were stool culture-positive for non-typhoidal
      Salmonella. Salmonella patients were more likely to be younger than controls
      (median age 10 and 12 months, respectively) [odds ratio (OR) 0?97; 95% confidence
      interval (CI) 0?94-0?99], to report a recent diarrhoeal contact (8?1% cases, 1?8%
      controls; OR 5?98, 95% CI 1?8-20?4) and to live in a household with >2 children
      (cases 20?8%, controls 10?2%; OR 2?32, 95% CI 1?2-4?7). Our findings indicate
      that Salmonella are an important cause of paediatric gastroenteritis in this
      setting and we suggest that transmission may occur through direct human contact
      in the home.

PMID- 23010149
TI  - Evolution of discrimination in populations at equilibrium between selfishness and
      altruism.
AB  - Where there is genetically based variation in selfishness and altruism, as in
      man, altruists with an innate ability to recognise and thereby only help their
      altruistic relatives may evolve. Here we use diploid population genetic models to
      chart the evolution of genetically-based discrimination in populations initially
      in stable equilibrium between altruism and selfishness. The initial stable
      equilibria occur because help is assumed subject to diminishing returns. Similar
      results were obtained whether we used a model with two independently inherited
      loci, one controlling altruism the other discrimination, or a one locus model
      with three alleles. The latter is the opposite extreme to the first model, and
      can be thought of as involving complete linkage between two loci on the same
      chromosome. The introduction of discrimination reduced the benefits obtained by
      selfish individuals, more so as the number of discriminators increased, and
      selfishness was eventually eliminated in some cases. In others selfishness
      persisted and the evolutionary outcome was a stable equilibrium involving selfish
      individuals and both discriminating and non-discriminating altruists. Heritable
      variation in selfishness, altruism and discrimination is predicted to be
      particularly evident among full sibs. The suggested coexistence of these three
      genetic dispositions could explain widespread interest within human social groups
      as to who will and who will not help others. These predictions merit experimental
      and observational investigation by primatologists, anthropologists and
      psychologists.

PMID- 23010150
TI  - The tobacco carcinogen nitrosamine induces a differential gene expression
      response in tumour susceptible A/J and resistant C3H mouse lungs.
AB  - The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), an
      important carcinogen found in tobacco products, causes lung cancer in genetically
      susceptible animals. In addition to mutations of the K-Ras gene, NNK has non
      mutagenic effects that include alterations in gene expression and
      immunomodulation in the lung. Here we report the identification of two gene sets
      associated with NNK-induced pulmonary tumourigenesis. First, to identify genes
      involved in the susceptibility to NNK, we compared the lung transcriptomes of NNK
      resistant C3H mice with that of the NNK-susceptible A/J mice, identifying
      differential expression of genes related to innate immunity and inflammation.
      Second, to identify gene expression induced by NNK, we compared the lung
      transcriptomes of C3H and A/J mice post-treatment. The Resistin-like alpha
      (Retnla) gene was highly upregulated in response to NNK only in susceptible mice.
      This gene product is known to recruit immune cells to the lung, and accumulation
      of CD45 positive cells in A/J lungs correlated with increased Retnla expression.
      Genetic susceptibility to NNK-induced lung tumourigenesis may relate in part to
      gene expression changes and alterations in the immune response to create a pro
      tumourigenic environment, acting in concert with NNK's mutagenic effects.

PMID- 23010151
TI  - The ABC transporter ABC40 encodes a phenylacetic acid export system in
      Penicillium chrysogenum.
AB  - The filamentous fungus Penicillium chrysogenum is used for the industrial
      production of beta-lactam antibiotics. The pathway for beta-lactam biosynthesis
      has been resolved and involves the enzyme phenylacetic acid CoA ligase that is
      responsible for the CoA activation of the side chain precursor phenylacetic acid
      (PAA) that is used for the biosynthesis of penicillin G. To identify ABC
      transporters related to beta-lactam biosynthesis, we analyzed the expression of
      all 48 ABC transporters present in the genome of P. chryso-genum when grown in
      the presence and absence of PAA. ABC40 is significantly upregulated when cells
      are grown or exposed to high levels of PAA. Although deletion of this transporter
      did not affect beta-lactam biosynthesis, it resulted in a significant increase in
      sensitivity to PAA and other weak acids. It is concluded that ABC40 is involved
      in weak acid detoxification in P. chrysogenum including resistance to
      phenylacetic acid.

PMID- 23010153
TI  - Oleanane-type triterpenoid saponins from Xanthoceras sorbifolia Bunge.
AB  - Phytochemical analysis of the extract from the seed oil leavings of Xanthoceras
      sorbifolia Bunge led to the isolation of five new oleanane-type triterpeniod
      saponins, sorbifoliasides G-K (1-5). Their structures were elucidated on the
      basis of spectroscopic analysis and chemical derivatization. To our knowledge,
      compound 5 is the first example of a naturally occurring 3,28-O-bisdesmosic
      triterpenoid saponin with olefinic linkages at C12 and C15. The cytotoxicity of
      all compounds against ten selected human cancer cell lines was assayed.

PMID- 23010154
TI  - Two pregnane derivatives and a quinolone alkaloid from Helicteres angustifolia.
AB  - Phytochemical investigation of the ethanol extract from roots of Helicteres
      angustifolia led to the isolation of two new pregnane derivatives, heligenin A-B
      (1-2), and a new quinolone alkaloid, helicterone A (3), along with thirteen known
      compounds (4-16). The structures of new compounds were established by analysis of
      extensive spectroscopic data. The absolute configuration of 1 was determined by
      application of the modified Mosher's method. All of the isolates were evaluated
      for their anti-proliferative activities against HT-29 human colon cancer cells
      and OVCA 429 ovarian cancer cells by MTT assay.

PMID- 23010152
TI  - A Paracoccidioides brasiliensis glycan shares serologic and functional properties
      with cryptococcal glucuronoxylomannan.
AB  - The cell wall of the yeast form of the dimorphic fungus Paracoccidioides
      brasiliensis is enriched with alpha1,3-glucans. In Cryptococcus neoformans,
      alpha1,3-glucans interact with glucuronoxylomannan (GXM), a heteropolysaccharide
      that is essential for fungal virulence. In this study, we investigated the
      occurrence of P. brasiliensis glycans sharing properties with cryptococcal GXM.
      Protein database searches in P. brasiliensis revealed the presence of sequences
      homologous to those coding for enzymes involved in the synthesis of GXM and
      capsular architecture in C. neoformans. In addition, monoclonal antibodies (mAbs)
      raised to cryptococcal GXM bound to P. brasiliensis cells. Using protocols that
      were previously established for extraction and analysis of C. neoformans GXM, we
      recovered a P. brasiliensis glycan fraction composed of mannose and galactose, in
      addition to small amounts of glucose, xylose and rhamnose. In comparison with the
      C. neoformans GXM, the P. brasiliensis glycan fraction components had smaller
      molecular dimensions. The P. brasiliensis components, nevertheless, reacted with
      different GXM-binding mAbs. Extracellular vesicle fractions of P. brasiliensis
      also reacted with a GXM-binding mAb, suggesting that the polysaccharide-like
      molecule is exported to the extracellular space in secretory vesicles. An
      acapsular mutant of C. neoformans incorporated molecules from the P. brasiliensis
      extract onto the cell wall, resulting in the formation of surface networks that
      resembled the cryptococcal capsule. Coating the C. neoformans acapsular mutant
      with the P. brasiliensis glycan fraction resulted in protection against
      phagocytosis by murine macrophages. These results suggest that P. brasiliensis
      and C. neoformans share metabolic pathways required for the synthesis of similar
      polysaccharides and that P. brasiliensis yeast cell walls have molecules that
      mimic certain aspects of C. neoformans GXM. These findings are important because
      they provide additional evidence for the sharing of antigenically similar
      components across phylogenetically distant fungal species. Since GXM has been
      shown to be important for the pathogenesis of C. neoformans and to elicit
      protective antibodies, the finding of similar molecules in P. brasiliensis raises
      the possibility that these glycans play similar functions in paracoccidiomycosis.

PMID- 23010155
TI  - Personalized primary tumor xenograft model established for the pre-clinical trial
      to guide postoperative chemotherapy.
AB  - Despite of the fact that a large amount of therapeutic agents have been developed
      for cancer treatment, we are still sometimes in a dilemma of choosing a most
      effective regimen for individual. With the reference of several recent
      researches, positive clinical correlations have been identified with primary
      tumor xenografts models, but limitations in existed models reveals a need for
      improvement. Over the past decade, conceptual progress has been made that tumors
      had increasingly been recognized as organs in which ostensibly normal cells as
      well as cancer cells participate actively in tumorigenesis by creating the "tumor
      microenvironment". Herein, we propose a hypothesis based on this novel conception
      that if transplanted as an organ, tumor implantation in nude mice would conserve
      most approximated biological traits with improved success rate, which make
      personalized tumor xenograft model practical for pre-clinical trials as
      substitutes for each patient. In our pilot study, intact tumor bloc was applied
      in implantation to evaluate this notion. As a result, 107 xenografts from all 20
      patients of gastric cancer were transplanted successfully. Pathological
      comparison confirmed that no differences between xenografts and primary tumors
      while the therapeutic response to two chemotherapeutic agents, docetaxel and
      pemetrexed, exhibited differently. In conclusion, applying personalized primary
      tumor xenograft model derived from freshly excised tumor in pre-clinic trails
      would potentially lead to a more effective customized chemotherapy.

PMID- 23010156
TI  - Stone gum: to prevent the stone migration and provide stone clearance during
      percutaneous nephrolithotomy.

PMID- 23010157
TI  - Medico-religiousplantsusedbytheHajongcommunityofAssam,India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Hajong people use many medicinal plants in
      their different rituals. The information generated from the present study
      regarding the medico-religious plants used by the Hajong tribes need a thorough
      phytochemical investigation. This could help in creating awareness regarding the
      need for conservation of such plants and also in the promotion of ethno-medico
      botany knowledge within the region besides contributing to the preservation and
      enrich- ment of the gene bank of such economically important species before they
      are lost forever. Medico-religious plants so found out in this study should be
      screened for their efficacy by which new drugs or products could be brought out.
      There is also need to document this information and compare with that of other
      tribes in the state and region. MATERIALS AND METHODS: The diseases found during
      the research work among the Hajong community were grouped in 11 categories. The
      category of diseases includes plants used for both human and animal diseases. The
      informants having good knowledge on medico-religious plants were chosen for the
      interview. Kabiraj or Vaidyas were also included among the informants though they
      were not available in all villages. The informants were asked about the ritual
      and religious importance and the medicinal properties of the plants used in
      different cultural practices. RESULTS: Some 36 plant species including herbs,
      shrubs and trees are used for curing 51 different diseases with 63 formulations
      which are recorded during the study. Most of the medicinal plants were collected
      from their own homestead and rest from the forest. Hajongs make sustainable use
      of available natural resources that include both medicinal and religious plants.
      They lead a much disciplined life. They are very much religious and
      knowledgeable. The survey revealed that not only the Kabiraj but also the elder
      community member have good knowledge of the medicinal value of some plant usually
      those species used to treat common diseases like cough, cold, fever, viral fever,
      headache, stomachache, joint pain, diarrhea, dysentery, minor wounds and cuts
      etc. Thus 36 plants are found to be used by Hajong in different medico-religious
      practices. These are regarded as holy plants. These plants are strictly protected
      by the community. Traditional conservation and management on cultural grounds,
      therefore, represents a historic contribution to the present day rich
      biodiversity in the region. CONCLUSION: The whole life system and socio-economic
      as well as religious and cultural activities of Hajongs were totally dependent
      upon forests. It reflected their high possession of knowledge on medico religious
      plants which allowed them to apply their indigenous knowledge regarding various
      aspects of exploitation of such resources. Different types of important species
      have been disappeared from the study area, which ultimately creates social,
      economical and religious problem in Hajong community. The information generated
      from the present study regarding the medico-religious plants used by the Hajong
      tribes need a thorough phytochemical investigation. This could help in creating
      awareness regarding the need for conservation of such plants and also in the
      promotion of ethno-medico-botany knowledge within the region besides contributing
      to the preservation and enrichment of the gene bank of such economically
      important species before they are lost forever. Traditional culture in different
      Hajong populated areas is very fast declining with lot of traditional knowledge
      under the influence of dominant culture. Cultural diversity conservation is
      needed urgently.

PMID- 23010158
TI  - Single-port thoracoscopic surgery can be a first-line approach for elective
      thoracoscopic surgery.
AB  - BACKGROUND: Thoracoscopic surgery has become very popular in recent years.
      Conventional thoracoscopic surgery requires three or more port wounds for
      manipulations of endoscopic instruments. For complicated cancer surgery, more
      port wounds and a larger thoracotomy wound may be required due to technical
      reasons. We want to investigate the effectiveness of single-port thoracoscopic
      approach in elective thoracoscopic surgery for thoracic disease. MATERIALS AND
      METHODS: From July 1st, 2010 to March 31, 2011, 90 consecutive patients underwent
      general thoracoscopic surgery performed by the same thoracic surgeon. Two
      patients with severe trauma and massive bleeding were excluded from the study.
      All patients included had thoracoscopic surgery with a single-port approach. The
      surgical outcomes, complications, mortality and conversion rates were recorded
      and analyzed. RESULTS: A total of 88 patients were included in this study. All
      these patients were operated on by the same surgeon. For sixty-eight patients,
      the single-port thoracoscopic approach was used. Nineteen patients were changed
      to a two-port thoracoscopic approach and one patient's was changed to mini
      thoracotomy. Two patients died from terminal lung cancer and severe mitral
      regurgitation. Complications occurred in six cases. Eighty-seven patients (98.8%)
      were effectively managed with either single-port or a two-port approach. Only one
      patient was managed by mini-thoracotomy. CONCLUSION: Elective thoracoscopic
      surgery performed through a single-port wound is feasible. Single-incisional
      thoracoscopic surgery can be safely applied as a first-line approach in most
      cases of elective thoracoscopic procedures.

PMID- 23010159
TI  - Vasoreactivity before and after handgrip training in chronic heart failure
      patients.
AB  - The purpose of this study was to investigate the vasodilatory and vasoconstrictor
      responses of the brachial artery in patients with chronic heart failure (CHF) and
      controls (CON) before and after a period of training and detraining. METHODS: CHF
      (n = 10; age = 62 +/- 8 yrs) and CON (n = 10; age = 55 +/- 5 yrs) subjects
      completed 4 weeks of bilateral handgrip training (20 min; 60% of maximal handgrip
      strength; 15 grips*min(-1); 4 days*week(-1)). Handgrip strength was measured
      using a hand dynamometer. Brachial artery flow-mediated dilation (BAFMD) and cold
      pressor test (CPT) responses were determined using ultrasonography prior to
      training, at the end of 4 weeks of training and following 4 weeks of detraining.
      Absolute (mm) BAFMD and CPT responses were combined to yield a vascular operating
      range (VOR). RESULTS: Baseline BAFMD was higher in CON (CHF: 2.98 +/- 1.49%; CON:
      6.21 +/- 1.21%; p = 0.01), while CPT responses were higher in CHF (CHF: 3.38 +/-
      0.83%; CON: 2.46 +/- 0.62%; p = 0.05). Baseline VOR tended to be greater in the
      CON subjects (CHF: 0.28 +/- 0.05 mm; CON: 0.32 +/- 0.12 mm; p = 0.06). Training
      increased handgrip strength (~5%; p < 0.05, for both groups), BAFMD (CHF: 2.98 +/
      1.49% to 3.75 +/- 1.56%; CON: 6.21 +/- 1.21% - 8.02 +/- 1.75%; p = 0.01) and VOR
      (CHF: 0.28 +/- 0.05 mm - 0.3 +/- 0.09 mm; CON: 0.32 +/- 0.12 mm - 0.42 +/- 0.11
      mm; p = 0.01). There were no significant changes in CPT responses. All markers
      approached pre-training values following detraining. CONCLUSION: Handgrip
      exercise increases strength, BAFMD and VOR in both CHF and CON subjects. These
      improvements are transient and return to pre-training values after removal of the
      training stimulus.

PMID- 23010160
TI  - Anatomo-clinical and molecular description of liver neotropical echinococcosis
      caused by Echinococcus oligarthrus in human host.
AB  - Since humans rarely play the role as Echinococcus oligarthrus host, there is lack
      of knowledge about the complex infectious process. Only three cases have been
      reported to occur in humans in the neotropics until now. We present the anatomo
      clinical and molecular findings describing a new case of infection by E.
      oligarthrus in a man. The muscular or subcutaneous tissues tropism described for
      this species in the previously reported cases was not present, but a liver
      tropism was observed. Additionally, the larval stage rostellar hooks morphometry
      differed from E. oligarthrus in the other human cases.

PMID- 23010161
TI  - Parasitological and malacological surveys reveal urogenital schistosomiasis on
      Mafia Island, Tanzania to be an imported infection.
AB  - To confirm the local endemicity of Schistosoma haematobium on Mafia Island,
      Tanzania, conjoint parasitological and malacological surveys were undertaken in
      July 2006 with parasitological investigations supplemented with case-history
      questionnaires. A total of 238 children (125 girls and 113 boys, mean age of 13.9
      years) across 9 primary schools were examined. The prevalence of micro-haematuria
      and egg-patent infection was 18.1% (CI95=9.6-33.6) and 4.2% (CI95=1.9-7.6),
      respectively but a strong female bias was observed for micro-haematuria (5.6F:1M)
      contrasting with a strong male bias for the presence of eggs (1F:4M). All egg
      patent infections were of light-intensity (<10eggs/10ml). No clear associations
      between infection prevalence and local water-contact, by school, were found and
      all 10 of the egg-positive children had a travel history to the nearby mainland
      or Zanzibar. Inspection of community diagnostic registers at Kilindoni Hospital
      revealed a low proportion (<2%) of egg-patent infection for 20,306 samples tested
      in the 2000-2005 period. A total of 43 freshwater sites, a third of which were
      previously sampled in 1999 and 2002, were surveyed and 11 species of freshwater
      mollusc were found. Four species of Bulinus (B. nasutus, B. forskalii, B. barthi
      and B. sp.) were encountered across 13 sites with B. nasutus restricted to 3 of
      these towards the north of the island. No collected snail was observed to shed
      schistosome cercariae. Further characterisation of B. nasutus and S. haematobium
      included infection challenge on two occasions, with miracidia obtained from egg
      patent children from Mafia and Unguja islands as well as DNA barcoding of snails
      and schistosomes. B. nasutus was shown refractory to infection. With the
      substantial travel to and from Mafia, the refractory nature of local snails and
      evidence from DNA barcoding in schistosomes and snails, we conclude that
      urogenital schistosomiasis is an imported infection.

PMID- 23010162
TI  - Cloning of cDNAs and molecular characterisation of C-type lectin-like proteins
      from snake venoms.
AB  - C-type lectin-like proteins (CTLPs) isolated from snake venoms are the largest
      and most complex non-mammalian vertebrate C-type lectin-like domain family. In
      the present study, we simultaneously amplified four cDNAs encoding different
      types of CTLP subunits from the venoms of two different species of snakes by RT
      PCR with a single sense primer and a nested universal primer - two CTLP subunit
      encoding cDNAs were cloned from Deinagkistrodon acutus venom and two from
      Agkistrodon halys Pallas venom. All four cloned CTLP subunits exhibited typical
      motifs in their corresponding domain regions but with relatively-low sequence
      similarities to each other. Compared with previously-published CTLPs, the four
      cloned CTLPs subunits showed slight variations in the calcium-binding sites and
      the disulphide bonding patterns. To our knowledge, these data constitute the
      first example of co-expression of CTLP platelet glycoprotein Ib-binding subunits
      and coagulation factors in Agkistrodon halys Pallas venom.

PMID- 23010163
TI  - The continuing saga of snake venom disintegrins.
AB  - Disintegrins, a family of polypeptides released in the venoms of viperid snakes
      (vipers and rattlesnakes) by the proteolytic processing of multidomain
      metalloproteinases, selectively block the function of beta(1) and beta(3)
      integrin receptors. Few of the proteins isolated and characterized from snake
      venoms have proven to be more structural and functional versatile than the
      disintegrins. Not surprisingly, 25 years after their discovery, our knowledge on
      the evolutionary history and the molecular determinants modulating the integrin
      inhibitory activity of disintegrins still remain fragmentary. This paper
      highlights some seminal contributions, including personal accounts of pioneer
      authors, related to basic and applied research on disintegrins. Investigators
      have evaluated disintegrin applications in therapies for a number of pathologies
      in which integrin receptors play relevant roles, particularly myocardial
      infarction and inappropriate tumor angiogenesis. Completing the continuing story
      of the disintegrin family by applying novel research approaches may hold the key
      to learn how to use deadly toxins as therapeutic agents.

PMID- 23010164
TI  - The long road of research on snake venom serine proteinases.
AB  - It has long been recognized that snake venom serine proteinases (SVSPs) affect
      various physiological functions including blood coagulation, fibrinolysis, blood
      pressure and platelet aggregation. Therefore, SVSPs have been used as refined
      tools to study molecular mechanisms involved in the activation of key factors
      that control hemostasis and as therapeutic agents in various thrombotic and
      hemostatic conditions. The aim of this review is to highlight the state of our
      knowledge on the advances made in SVSP research since the 18th century. It
      includes the personal accounts of some distinguished scientists that addressed
      specific problems and contributed to advance the field.

PMID- 23010165
TI  - A brief review of the scientific history of several lesser-known snake venom
      proteins: l-amino acid oxidases, hyaluronidases and phosphodiesterases.
AB  - When considering the proteins and toxins in snake venom one's thoughts generally
      migrate to the proteinases, neurotoxins and phospholipases since these families
      of proteins are comprised by many of the toxins found in venom. However as modern
      proteomic and transcriptomic venom research has abundantly shown snake venoms are
      complex and containing numerous families of protein beyond the "big three". In
      this brief review we will discuss three of the lesser discussed proteins
      typically found in snake venoms: l-amino acid oxidases (LAAO); hyaluronidases and
      phosphodiesterases. These proteins have long been known to be part of many
      venoms' proteomes with reports appearing in the literature as early as 1944 for
      LAAO, 1947 for hyaluronidase (spreading factor), and 1932 for venom
      phosphodiesterase. These are more or less contemporary with the first reports
      (circa 1950) on snake venom proteases. Thus, the relatively modest literature on
      these snake venom proteins stems not from lack of early discovery but rather more
      likely to their ostensibly minor role in snake venom pathophysiology. In this
      review we will provide an overview of the experimental history of these venom
      proteins, their biochemical and structural features and their role in snake venom
      toxinology with the aim of bringing a fuller, more comprehensive, understanding
      of the history of laboratory research on snake venoms. In addition, there are
      some comments on these proteins from investigators who were actively engaged in
      their investigation.

PMID- 23010166
TI  - Venom and cnidome ontogeny of the cubomedusae Chironex fleckeri.
AB  - This is the first study to explore venom and cnidome variation of individual
      cubomedusae, Chironex fleckeri, of different ages and from different regional
      locations in relation to feeding ecology. As medusae matured the proportion of
      mastigophores (those nematocysts containing the lethal venom component) in the
      cnidome increased, along with proportion of the vertebrate toxic fraction, in the
      venom profile. This switch in cnidome and venom occurred at the seven to ten
      tentacle stage. Whole venom was found to be toxic specifically to vertebrate
      cardiac cells, as opposed to vertebrate skeletal cells, and dose dependent, along
      with the vertebrate toxic fraction. The venom and cnidome ontogeny, along with
      venom toxicity, is correlated with C. fleckeri's known feeding ecology. Large and
      mature C. fleckeri feed predominantly on vertebrates, and have a greater
      proportion of mastigophores in their cnidome along with more vertebrate toxic
      fraction in their venom, compared to when they are young and small feeding on
      invertebrates.

PMID- 23010167
TI  - Surgical versus conservative treatment in patients with cerebral cavernomas and
      non refractory epilepsy.
AB  - PURPOSE: The optimal therapy of patients with cerebral cavernoma (CCs) and new
      onset epilepsy, sporadic seizures, or non well established refractory epilepsy is
      still not clear. The aim of this study was to compare the incidence of seizures
      in patients with CCs both operated and non operated, in order to obtain more
      information on the correct management of these patients. MATERIALS AND METHODS:
      We studied retrospectively 43 patients with non refractory epilepsy secondary to
      CCs. Twenty-six of them (60.5%) underwent surgery and made up the surgical group,
      and 17 patients were treated medically and constituted the medical group. Seizure
      frequency and other clinical variables were compared between both groups.
      RESULTS: At two years, out of the 26 operated patients, 19 (73%) remained seizure
      free, 4 (15%) had less than a seizure per month, and one patient (4%) had more
      than one seizure per month. At five years, 15 patients of the surgical group
      remained for analysis. Of them, 11 (73.3%) were seizure free, and 4 (26.7%) had
      less than one seizure a month. In the medical group, 12 out of 17 patients were
      seizure free (70.6%). There were no significant differences between the two
      groups (p=0.2 and p=0.3, respectively). Seven patients had postoperative
      neurological sequelae. CONCLUSION: Surgical treatment of patients with non
      refractory epilepsy due to CCs did not significantly reduce the likelihood of
      seizures when compared to medical treatment. It must also be considered that
      surgery carries serious risks. A prospective and randomized study must be carried
      out to further clarify our findings.

PMID- 23010168
TI  - A functional nuclear localization sequence in the VP1 capsid protein of
      coxsackievirus B3.
AB  - The capsid proteins of some RNA viruses can translocate to the nucleus and
      interfere with cellular phenotypes. In this study we found that the VP1 capsid
      protein of coxsackievirus B3 (CVB3) was dominantly localized in the nucleus of
      the cells transfected with VP1-expressing plasmid. The VP1 nuclear localization
      also occurred in the cells infected with CVB3. Truncation analysis indicated that
      the VP1 nuclear localization sequence located near the C-terminal. The
      substitution of His220 with threonine completely abolished its translocation. The
      VP1 proteins of other CVB types might have the nuclear localization potential
      because this region was highly conserved. Moreover, the VP1 nuclear localization
      induced cell cycle deregulation, including a prolonged S phase and shortened G2-M
      phase. Besides these findings, we also found a domain between Ala72 and Phe106
      that caused the VP1 truncates dotted distributed in the cytoplasm. Our results
      suggest a new pathogenic mechanism of CVB.

PMID- 23010169
TI  - AMP-activated protein kinase: implications on ischemic diseases.
AB  - Ischemia is a blockage of blood supply due to an embolism or a hemorrhage in a
      blood vessel. When an organ cannot receive oxygenated blood and can therefore no
      longer replenish its blood supply due to ischemia, stresses, such as the
      disruption of blood glucose homeostasis, hypoglycemia and hypoxia, activate the
      AMPK complex. LKB1 and CaMKKbeta are essential activators of the AMPK signaling
      pathway. AMPK triggers proangiogenic effects through the eNOS protein in tissues
      with ischemic conditions, where cells are vulnerable to apoptosis, autophagy and
      necrosis. The AMPK complex acts to restore blood glucose levels and ATP levels
      back to homeostasis. This review will discuss AMPK, as well as its key activators
      (LKB1 and CaMKKbeta), as a central energy regulator and evaluate the upstream and
      downstream regulating pathways of AMPK. We will also discuss how we can control
      this important enzyme in ischemic conditions to prevent harmful effects in
      patients with vascular damage.

PMID- 23010170
TI  - The roles of FADD in extrinsic apoptosis and necroptosis.
AB  - Fas-associated protein with death domain (FADD), an adaptor that bridges death
      receptor signaling to the caspase cascade, is indispensible for the induction of
      extrinsic apoptotic cell death. Interest in the non-apoptotic function of FADD
      has greatly increased due to evidence that FADD-deficient mice or dominant
      negative FADD transgenic mice result in embryonic lethality and an immune defect
      without showing apoptotic features. Numerous studies have suggested that FADD
      regulates cell cycle progression, proliferation, and autophagy, affecting these
      phenomena. Recently, programmed necrosis, also called necroptosis, was shown to
      be a key mechanism that induces embryonic lethality and an immune defect.
      Supporting these findings, FADD was shown to be involved in various necroptosis
      models. In this review, we summarize the mechanism of extrinsic apoptosis and
      necroptosis, and discuss the in vivo and in vitro roles of FADD in necroptosis
      induced by various stimuli.

PMID- 23010171
TI  - Biphasic effects of TGFbeta1 on BMP9-induced osteogenic differentiation of
      mesenchymal stem cells.
AB  - We have found that the previously uncharacterized bone morphogenetic protein-9
      (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9
      cross-talks with TGFbeta1 during osteogenic differentiation. Using the
      recombinant BMP9 adenovirus, we find that low concentration of rhTGFbeta1
      synergistically induces alkaline phosphatase activity in BMP9-transduced
      C3H10T1/2 cells and produces more pronounced matrix mineralization. However,
      higher concentrations of TGFbeta1 inhibit BMP9-induced osteogenic activity. Real
      time PCR and Western blotting indicate that BMP9 in combination with low dose of
      TGFbeta1 potentiates the expression of later osteogenic markers osteopontin,
      osteocalcin and collagen type 1 (COL1a2), while higher concentrations of TGFbeta1
      decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle
      analysis reveals that TGFbeta1 inhibits C3H10T1/2 proliferation in BMP9-induced
      osteogenesis and restricts the cells in G(0)/G(1) phase. Our findings strongly
      suggest that TGFbeta1 may exert a biphasic effect on BMP9-induced osteogenic
      differentiation of mesenchymal stem cells.

PMID- 23010173
TI  - Nuclear Akt promotes neurite outgrowth in the early stage of neuritogenesis.
AB  - In addition to its pivotal role in neuronal survival, PI3K/Akt signaling is
      integral to neuronal differentiation and neurite outgrowth. However, the exact
      role of Akt in neuronal differentiation is still controversial. Here, we found
      that nuclear expression of CA-Akt resulted in unusual rapid neurite outgrowth and
      overexpression of KD-Akt caused multiple dendrite growth without specific axon
      elongation. Moreover, microarray data revealed that the expression of FOXQ1
      expression was about 10-fold higher in cells with nuclear, active Akt than in
      control cells. Quantitative real-time PCR analysis showed that mRNA levels were
      upregulated in NLS-CA-Akt cells as compared to KD or EV cells. Furthermore, our
      FACS analysis demonstrated that overexpression of NLS-CA-Akt accumulate cells in
      the G1 phase within 24 h, fitting with the rapid sprouting of neuritis. Thus, our
      data implied that at least in this early time frame, the overexpression of
      nuclear, active Akt forced cells into neurite development through probably
      FOXQ1regulation.

PMID- 23010172
TI  - Alternative splicing and expression analysis of High expression of osmotically
      responsive genes1 (HOS1) in Arabidopsis.
AB  - High expression of osmotically responsive genes1 (HOS1), a key regulator of low
      temperature response and flowering time, encodes an E3 ubiquitin ligase in
      Arabidopsis. Here, we report characterization of a newly identified splice
      variant (HOS1-L) of HOS1. Comparative analyses revealed that HOS1-L has a longer
      5' nucleotide sequence than that of the previously identified HOS1 (HOS1-S) and
      that its protein sequence was more conserved than that of HOS1-S in plants. HOS1
      L transcripts were spatio-temporally more abundant than those of HOS1-S. The
      recovery rate of HOS1-S expression was faster than that of HOS1-L after cold
      treatment. Diurnal oscillation patterns of HOS1-L revealed that HOS1-L expression
      was affected by photoperiod. An in vitro pull-down assay revealed that the HOS1-L
      protein interacted with the ICE1 protein. HOS1-L overexpression caused delayed
      flowering in wild-type plants. Collectively, these results suggest regulation of
      HOS1 expression at the post-transcriptional level.

PMID- 23010174
TI  - Parkin induces apoptotic cell death in TNF-alpha-treated cervical cancer cells.
AB  - Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-alpha)
      induced cell death during carcinogenesis. In the present study, we examined
      whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer
      cell line resistant to TNF-alpha-induced cell death. TNF-alpha-treatment alone
      did not affect HeLa cell viability. However, expression of parkin restored TNF
      alpha-induced apoptosis in HeLa cells. Increased cell death was due to the
      activation of the apoptotic pathway. Expression of parkin in TNF-alpha-treated
      HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, 
      7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted
      in decreased expression of the caspase inhibitory protein, survivin. These
      results suggest that parkin acts as a tumor suppressor in human cervical cancer
      cells by modulating survivin expression and caspase activity. We propose that
      this pathway is a novel molecular mechanism by which parkin functions as a tumor
      suppressor.

PMID- 23010175
TI  - PEP-1-p18 prevents neuronal cell death by inhibiting oxidative stress and Bax
      expression.
AB  - P18, a member of the INK4 family of cyclin-dependent kinase inhibitors, is a
      tumor suppressor protein and plays a key cell survival role in a variety of human
      cancers. Under pathophysiological conditions, the INK4 group proteins participate
      in novel biological functions associated with neuronal diseases and oxidative
      stress. Parkinson's disease (PD) is characterized by loss of dopaminergic
      neurons, and oxidative stress is important in its pathogenesis. Therefore, we
      examined the effects of PEP-1-p18 on oxidative stress-induced SH-SY5Y cells and
      in a PD mouse model. The transduced PEP-1-p18 markedly inhibited 1-methyl-4
      phenyl pyridinium-induced SH-SY5Y cell death by inhibiting Bax expression levels
      and DNA fragmentation. Additionally, PEP-1-p18 prevented dopaminergic neuronal
      cell death in the substantia nigra of a 1-methyl-4-phenyl-1,2,3,6,
      tetrahydropyridine-induced PD mouse model. These results indicate that PEP-1-p18
      may be a useful therapeutic agent against various diseases and is a potential
      tool for treating PD.

PMID- 23010176
TI  - Differential expression of cell surface markers in response to 2,4
      dinitrofluorobenzene in RAW 264.7 and primary immune cells.
AB  - We evaluated the expression of the costimulatory molecules CD80 and CD83 and
      major histocompatibility (MHC) class II induced by 2,4-dinitrofluorobenzene
      (DNFB) in the RAW 264.7 macrophage cell line. In contrast to the previously
      reported effect of DNFB on dendritic cells, CD86 expression did not change.
      Furthermore, we observed that the CD83 expression level transiently increased and
      then decreased. Induction of CD80 and MHC class II molecule expression and a
      decrease in CD83 expression by DNFB in vitro were also confirmed in splenocytes
      of BALB/c and NC/Nga mice. However, DNFB did not influence CD83 expression in
      peritoneal CD11b(+) cells from BALB/c or NC/Nga mice. Detailed in vivo
      experiments and further studies on the possible contribution of CD11b(+) cells to
      induce atopic dermatitis (AD) would be helpful to attain a better understanding
      of AD pathogenesis.

PMID- 23010177
TI  - The seasonal effect in one-dimensional Daisyworld.
AB  - We have studied the effects of seasonal Solar Radiation Forcing (SRF) on the
      climate self-regulatory capability of life, using a latitudinal-dependent
      Daisyworld model. Because the seasonal polarity of SRF increases poleward,
      habitable conditions exist in the equatorial regions year round, whereas, in the
      high latitudes, harsh winters cause annual extinction of life, and only the
      summers are inhabited or regulated by life. Seasonality affects climate
      regulation by two major mechanisms: (1) the cold winter conditions in the high
      latitudes reduce the global temperature below the optimal temperature; (2) during
      summer, life experiences higher SRF anomalies and, therefore, shifts to higher
      albedo when compared to annual mean SRF. In turn, a full capacity for temperature
      regulation is reached at lower SRF, and the range of SRF over which life
      regulates climate is significantly reduced. Lastly, initiation/extinction of life
      at low/highly-perturbed SRF occurs at the poles. Therefore, an irreversible
      global extinction occurs once life passes its regulatory capacity in the poles.
      We conduct extensive sensitivity analyses on various model parameters
      (latitudinal heat diffusion, heat capacity, and population death rate),
      strengthening the generality/robustness of the above net seasonal effects.
      Applications to other SRF fluctuation, as Milankovitch cycles are discussed.

PMID- 23010178
TI  - Prevalence and distribution of Cryptosporidium and Giardia in wastewater and the
      surface, drinking and ground waters in the Lower Rhine, Germany.
AB  - Samples from different water sources (n = 396) were collected during 2009 and
      2011. Wastewater (2-5 l) was purified by aluminium sulphate flocculation.
      Surface, ground and drinking waters (400-6400 l) were collected by filtration.
      Cryptosporidium oocysts and Giardia cysts were further concentrated by sucrose
      centrifugation. (Oo)cysts were identified by IFT (immunofluorescence test), DAPI
      (4',6-diamidino-2-phenylindole) staining and DICM (difference interference
      contrast microscopy). Out of 206 wastewater samples, 134 (65.0%) were found to be
      positive for Giardia cysts and 64 (31.1%) for Cryptosporidium oocysts. Parasite
      numbers ranged from 0 to 2436 cysts/l and 0 to 1745 oocysts/l. Eight (4.2%)
      surface and drinking water samples (n = 190) were found to be positive for
      Giardia cysts (0-56000/100 l), and 18 (9.5%) for Cryptosporidium oocysts
      (2400/100 l). The purpose of this study was to establish the prevalence and
      concentrations of Giardia lamblia and Cryptosporidium spp. by detecting (oo)cysts
      from water samples. This study provides substantial evidence that G. lamblia
      cysts and Cryptosporidium spp. oocysts are able to enter and circulate in the
      aquatic environment with negative implications for public health.

PMID- 23010179
TI  - Images in emergency medicine. Elderly male with respiratory failure. Chronic
      idiopathic intestinal pseudo-obstruction.

PMID- 23010180
TI  - Commentary: death on our nation's roadways: not just for cars.

PMID- 23010181
TI  - Clinical policy: critical issues in the prescribing of opioids for adult patients
      in the emergency department.

PMID- 23010182
TI  - Change of shift. Do you believe in miracles?

PMID- 23010183
TI  - Some think antibiotics are candy, but we know they're not: answers to the May
      2012 Journal Club Questions.

PMID- 23010184
TI  - Images in emergency medicine. A suddenly collapsed man. Neurogenic pulmonary
      edema.

PMID- 23010185
TI  - Procalcitonin of questionable value.

PMID- 23010186
TI  - Repeated CTs-let's use our heads.

PMID- 23010187
TI  - Pharmacologic prevention for acute mountain sickness-lack of appropriate
      inclusion of the available evidence.

PMID- 23010189
TI  - Ethylene glycol elimination kinetics and outcomes in patients managed without
      hemodialysis.

PMID- 23010191
TI  - Policy statement. Availability of hospital diagnostic and therapeutic services.

PMID- 23010192
TI  - Policy statement. Use of short courses in emergency medicine as criteria for
      privileging or employment.

PMID- 23010193
TI  - Policy statement. Good Samaritan protection.

PMID- 23010194
TI  - Images in emergency medicine. Fever, cough and weight loss. Miliary tuberculosis.

PMID- 23010195
TI  - Modulation of the expression of ryanodine receptor mRNA from Plutella xylostella
      as a result of diamide insecticide application.
AB  - Ryanodine receptors (RyRs), members of the largest family of calcium channel
      proteins, have been studied because of their key roles in calcium signalling
      within cells. With the development of diamide insecticides that exhibit a novel
      mode of action on the RyRs from Lepidoptera, research on insect RyRs has become
      more attractive in the field of plant protection. To enhance our understanding of
      the effects of diamides on RyRs, we cloned the Plutella xylostella RyR gene (Px
      RyR), which is the most serious pest of Brassicaceae plants throughout the world.
      Furthermore, we investigated the modulation of the expression of Px-RyR as a
      result of the application of diamide insecticides. The full-length cDNAs of Px
      RyR contain an open reading frame (ORF) of 15,372bp with a predicted protein
      consisting of 5123 amino acids. Px-RyR possesses a high level of overall amino
      acid homology with other isoforms (77-92% identity with insect isoforms and 45
      47% identity with vertebrate isoforms). The weight of Px. gradually decreased as
      the concentration of the diamides increased. However, the relative expression
      levels of the RyRs from larvae were dependent on the insecticide concentration
      and gradually increased with increasing insecticide concentrations.

PMID- 23010196
TI  - Patterns of cis-element enrichment reveal potential regulatory modules involved
      in the transcriptional regulation of anoxia response of japonica rice.
AB  - Unlike other cereal species, rice is able to germinate and elongate under anoxia.
      The regulatory mechanism that configures the transcriptome of rice during
      anaerobic germination is yet to be established. In this study, the major
      regulatory modules among anoxia-responsive genes in rice identified from
      published microarray data were predicted by ab initio analysis of cis-regulatory
      information content. Statistically overrepresented sequence motifs were detected
      from bona fide promoter sequences [-1000 to +200], revealing various patterns of
      cis-element enrichment that are highly correlated with bZIP, ERF and MYB types of
      transcription factors. As implied by the cis-element enrichment patterns,
      combinatorial mechanisms configure the overall changes in gene expression during
      anoxic germination and coleoptile elongation. High enrichment of cis-elements
      associated with ARF, bZIP, ERF, MYB and WRKY (SUSIBA2) transcription factors was
      also detected among the glycolytic and fermentative associated genes that were
      upregulated during anoxia. The patterns established from the global analysis of
      cis-element distribution for upregulated and downregulated genes and their
      associations with potential cognate regulatory transcription factors indicate the
      significant roles of ethylene and abscisic acid mediated signaling during
      coleoptile elongation under anoxia. In addition, the regulation of genes encoding
      enzymes in the glycolytic and fermentative metabolism could be associated with
      abscisic acid and auxin in rice coleoptiles to maintain sugar and ATP levels for
      longer survival.

PMID- 23010197
TI  - Molecular and expression characterization of a nanos1 homologue in Chinese
      sturgeon, Acipenser sinensis.
AB  - The nanos gene family was essential for germ line development in diverse
      organisms. In the present study, the full-length cDNA of a nanos1 homologue in A.
      sinensis, Asnanos1, was isolated and characterized. The cDNA sequence of Asnanos1
      was 1489 base pairs (bp) in length and encoded a peptide of 228 amino acid
      residues. Multiple sequence alignment showed that the zinc-finger motifs of
      Nanos1 were highly conserved in vertebrates. By RT-PCR analysis, Asnanos1 mRNAs
      were ubiquitously detected in all tissues examined except for the fat, including
      liver, spleen, heart, ovary, kidney, muscle, intestines, pituitary, hypothalamus,
      telencephalon, midbrain, cerebellum, and medulla oblongata. Moreover, a specific
      polyclonal antibody was prepared from the in vitro expressed partial AsNanos1
      protein. Western blot analysis revealed that the tissue expression pattern of
      AsNanos1 was not completely coincided with that of its mRNAs, which was not found
      in fat, muscle and intestines. Additionally, by immunofluoresence localization,
      it was observed that AsNanos1 protein was in the cytoplasm of primary oocytes and
      spermatocytes. The presented results indicated that the expression pattern of
      Asnanos1 was differential conservation and divergence among diverse species.

PMID- 23010198
TI  - Identification of a novel ZNF469 mutation in a large family with Ehlers-Danlos
      phenotype.
AB  - Brittle cornea syndrome (BCS) is a genetically heterogeneous disorder
      characterized by extreme corneal fragility and thinning, which may lead to
      spontaneous or trauma-induced corneal rupture. BCS-1 and BCS-2 are caused by
      recessive mutations in ZNF469 and PRDM5, respectively. Both genes play a role in
      the regulatory pathway of corneal development and maintenance. We report a
      consanguineous family with five patients affected with the cardinal ocular
      features of BCS and significant musculoskeletal findings primarily in the form of
      joint hypermobility and severe kyphoscoliosis. The patients had thin velvety
      skin, hallux valgus, variable sensorineural hearing loss and arachnodactyly.
      Interestingly, one of the patients additionally had phenylketonuria and showed a
      milder ophthalmological and musculoskeletal phenotype than his affected siblings.
      The urinary pyridinoline and deoxypyridinoline concentrations and their ratios
      were mildly elevated indicating increased bone-collagen turnover. A novel
      homozygous 14 bp duplication in exon 2 of ZNF469 (c.8817_8830dup) was uncovered
      by direct sequencing. This family highlights the phenotypic overlap between BCS
      and Ehlers-Danlos syndrome.

PMID- 23010199
TI  - Molecular basis of albinism in India: evaluation of seven potential candidate
      genes and some new findings.
AB  - Albinism represents a group of genetic disorders with a broad spectrum of
      hypopigmentary phenotypes dependent on the genetic background of the patients.
      Oculocutaneous albinism (OCA) patients have little or no pigment in their eyes,
      skin and hair, whereas ocular albinism (OA) primarily presents the ocular
      symptoms, and the skin and hair color may vary from near normal to very fair.
      Mutations in genes directly or indirectly regulating melanin production are
      responsible for different forms of albinism with overlapping clinical features.
      In this study, 27 albinistic individuals from 24 families were screened for
      causal variants by a PCR-sequencing based approach. TYR, OCA2, TYRP1, SLC45A2,
      SLC24A5, TYRP2 and SILV were selected as candidate genes. We identified 5 TYR and
      3 OCA2 mutations, majority in homozygous state, in 8 unrelated patients including
      a case of autosomal recessive ocular albinism (AROA). A homozygous 4-nucleotide
      novel insertion in SLC24A5 was detected in a person showing with extreme
      cutaneous hypopigmentation. A potential causal variant was identified in the
      TYRP2 gene in a single patient. Haplotype analyses in the patients carrying
      homozygous mutations in the classical OCA genes suggested founder effect. This is
      the first report of an Indian AROA patient harboring a mutation in OCA2. Our
      results also reveal for the first time that mutations in SLC24A5 could contribute
      to extreme hypopigmentation in humans.

PMID- 23010200
TI  - Association of TCF7L2 gene polymorphisms with type 2 diabetes mellitus in Han
      Chinese population: a meta-analysis.
AB  - Variants of transcription factor 7-like 2 (TCF7L2) gene have been reported to be
      associated with type 2 diabetes mellitus (T2DM), but the available data on this
      relationship are inconsistent in Han Chinese populations. A meta-analysis was
      performed to quantitatively analyze the association of TCF7L2 gene polymorphisms
      with T2DM using previous case-control studies in Chinese Han populations. Several
      electronic databases were searched for relevant articles up to May 2012. After
      data collection and gene loci selection, a meta-analysis was performed to assess
      heterogeneity, combine results and evaluate variations. Publication bias was
      examined by the Egger's linear regression test. Hardy-Weinberg equilibrium (HWE)
      test and by omitting one study at a time were employed for the sensitivity
      analysis. Eighteen studies from sixteen eligible papers were included in the meta
      analysis. Ten eligible studies were analyzed for rs7903146, and eight were
      analyzed for rs290487. We found that the rs7903146 T allele was associated with
      an increased risk for T2DM under a dominant model, a co-dominant model and an
      allele contrast model, with an OR of 1.54 (1.32, 1.79), an OR of 1.53 (1.31,
      1.79) and an OR of 1.52 (1.31, 1.76), respectively. The rs290487 C allele showed
      no significant overall association with T2DM, yielding ORs of 1.08 (0.88, 1.32)
      under a dominant model, with strong evidence of heterogeneity. Similar results
      were also obtained in other genetic models. Sensitivity analysis confirmed the
      reliability and stability of this meta-analysis. The accumulated evidence
      suggested that the rs7903146 T allele was associated with an increased risk for
      T2DM, but the rs290487 C allele is not associated with T2DM in the Chinese Han
      population. More well-designed large studies are required for the validation of
      this association.

PMID- 23010201
TI  - Elimination of permanent injuries to the inferior alveolar nerve following
      surgical intervention of the "high risk" third molar.
AB  - We aimed to find out whether improved preoperative assessment and surgical
      planning with cone beam computed tomography (CT) could reduce damage to the
      inferior alveolar nerve when high risk impacted mandibular third molars are
      extracted. We recorded the presence or absence of postoperative neuropathy after
      extraction of 200 lower third molars in 185 patients (where cone beam CT had
      shown contact between the nerve and root) after treatment in the oral surgery
      department of King's College Hospital. All patients had had cone beam CT of the
      teeth after panoramic radiography had indicated increased risk of injury to the
      nerve during extraction. Experienced oral surgeons did all the operations and
      postoperative reviews. Patients reported temporary alteration of sensation after
      operation in 12% of teeth but it resolved in all cases and no patient reported
      permanent loss of sensation. Permanent sensory disturbance in the distribution of
      the inferior alveolar nerve after third molars have been removed can be
      eliminated in high risk cases if operations are planned carefully (including cone
      beam CT), and the procedure is done by a skilled surgeon who has an appreciation
      of the anatomy of the nerve and roots, and an insight into the mechanical effect
      of their surgical manipulation. The incidence of permanent neurosensory
      dysfunction in this study was zero even though all teeth were intimately related
      to the inferior alveolar canal.

PMID- 23010202
TI  - From "blockbusters" to "biosimilars": an opportunity for patients, medical
      specialists and health care providers.
AB  - Advances in basic research and research and development plans of pharmaceutical
      companies are radically changing the kind of available drugs and therapeutic
      targets. We are switching from predominantly chemical molecules, aimed at
      treating large populations of patients (blockbuster drugs), to a new generation
      of products, mostly biotech, aimed at modifying a specific pathogenetic
      mechanism. In other word we are moving fast to targeted therapy, which represents
      the first step toward personalized therapy, where the right drug at the right
      dose is administered to the right person, at the right time. Like the patent
      expiration of chemical products has corresponded to the development of generic
      drugs, the expiration of new biotech products will witness the appearance of
      biosimilars. The latter are biologic products that are highly similar but not
      identical to the reference medical products in terms of quality, safety and
      efficacy. This implies specific research, clinical monitoring, physicians
      updating of knowledge for a safe and appropriate use of these products. We are
      the beginning of a devolution in patient's care and physicians' practice.

PMID- 23010203
TI  - Complete radiologic response and long-term survival with use of systemic high
      dose methotrexate for breast cancer-associated leptomeningeal disease.

PMID- 23010204
TI  - From DAS 28 to SAS 1.

PMID- 23010205
TI  - Lotus seed epicarp extract as potential antioxidant and anti-obesity additive in
      Chinese Cantonese Sausage.
AB  - The antioxidative activities of a lotus seed epicarp extract in different
      concentrations (6.25, 12.5, 25, 50 and 100 MUg.mL(-1)) in pork homogenates
      representative of Chinese Cantonese Sausage were evaluated using three methods:
      thiobarbituric acid-reactive substances (TBARS) values, peroxide values (POVs)
      and acid values (AVs). Also the cytotoxic and anti-obesity effects of the lotus
      seed epicarp extracts were evaluated using an in vitro 3T3-L1 preadipocyte cell
      model. Results showed that the lotus seed epicarp extracts were non-toxic and
      effective in inhibiting preadipocyte differentiation. Supplementation of pork
      homogenate with lotus seed epicarp extracts was effective in retarding lipid
      oxidation. Moreover, the antioxidative and preadipocyte differentiation
      inhibition effects of the lotus seed epicarp extracts were dose-dependent. Thus,
      the lotus seed epicarp extract might be a good candidate as an antioxidant and
      anti-obesity natural additive in Chinese Cantonese Sausage.

PMID- 23010206
TI  - Fatty acid composition of adipose tissue and muscle from Jersey steers was
      affected by finishing diet and tissue location.
AB  - To determine the impacts of finishing diet and tissue type and location on fatty
      acid composition and palatability of Jersey beef, twenty steers were assigned to
      a factorial treatment design with initial weight (Light vs. Heavy) and finishing
      diet (70 vs. 85% concentrate) as treatments. Ribeye steaks were collected for
      sensory evaluation. Muscle, seam and subcutaneous (s.c.) fat from steaks, kidney
      fat (KF) and omental fat (OMF) were collected for fatty acid analysis. Initial
      weight and finishing diet had little impact on beef palatability. The 85%
      concentrate decreased polyunsaturated fatty acids (PUFA) in muscle and increased
      trans fatty acids in all tissues (P<0.05). The monounsaturated:saturated fatty
      acid ratio (MUFA:SFA) was highest in s.c. fat, intermediate in muscle and seam
      fat, and lowest in KF and OMF. The PUFA:SFA was highest in muscle, intermediate
      in s.c. and seam fat, and lowest in KF and OMF. Fatty acid composition differed
      greatly among tissues and the lower concentrate diet increased omega-3 and PUFA
      percentages in muscle.

PMID- 23010207
TI  - Effects of lairage time on welfare indicators, energy metabolism and meat quality
      of pigs in Beijing.
AB  - A total of forty Duroc-Landrace-Large White female pigs (90 +/- 5 kg) were used
      to study the effects of different lairage times (0 h, 3h, 8 h, 24 h) on welfare,
      energy metabolism and meat quality. The results showed that lairage time of 3h
      led to a lower blood cortisol, a decreased drip loss and a delayed degradation of
      glycogen in muscles compared with pigs without rest, while lairage times of 8h
      and 24h resulted in a significant increase in pork toughness. It was concluded
      that three hours of lairage was appropriate to reduce pre-slaughter stress and
      obtain better meat quality for pigs transported for 4h in winter, under the most
      frequent commercial conditions in Beijing, China. No lairage, or excessively long
      lairage time, might compromise animal welfare and meat quality.

PMID- 23010208
TI  - Thermodynamic analysis of a high-yield biochemical process for biofuel
      production.
AB  - This paper presents a thermodynamic analysis of a high-yield biochemical process
      for biofuel production from lignocelluosic biomass based on a previously proposed
      process. Unlike the standard biochemical process, which ferments sugar
      intermediates to ethanol, the process under consideration converts sugars to
      acetic acid which is esterified and hydrogenated to produce ethanol. This process
      has a significantly higher yield and produces no carbon dioxide. However, we find
      that the thermodynamic efficiency of the process is not increased in proportion
      to the yield gain. An additional survey of various biofuel production processes
      showed no direct correlation between yield and thermodynamic efficiency. This
      survey and the detailed thermodynamic analyses lead us to conclude that yield
      alone is an unreliable performance metric for biofuel technologies.

PMID- 23010209
TI  - Characterization of denitrifying granular sludge with and without the addition of
      external carbon source.
AB  - In this study granular sludge taken from a denitrifying upflow sludge reactor was
      characterized. Denitrification rates were determined in batch tests with and
      without external carbon source addition and pH microprofiles of the granules were
      studied. The microbial community structure was also determined. The results
      showed that denitrification without carbon source addition occurs; however, the
      process rate was lower than with external carbon source. This suggests that
      bacteria use dead biomass and extracellular material in the granular sludge as a
      carbon source when readily available substrate has been exhausted and nitrate is
      still present. Microprofiles showed a slight pH decrease for denitrification
      without external carbon source addition, and an increase in pH when using nitrite
      as the electron acceptor. Microprofiles using acetate as the carbon source for
      denitrification showed a significant increase in pH. Clone sequences obtained
      were close to the species Vitellibacter sp., Denitromonas indolicum str. and
      Denitromonas aromaticaus sp.

PMID- 23010210
TI  - Integrated multiplex ligation dependent probe amplification (MLPA) assays for the
      detection of alterations in the HEXB, GM2A and SMARCAL1 genes to support the
      diagnosis of Morbus Sandhoff, M. Tay-Sachs variant AB and Schimke immuno-osseous
      dysplasia in humans.
AB  - Multiplex ligation dependent probe amplification (MLPA) assays were designed for
      the genes HEXB (OMIM: 606873), GM2A (OMIM: 613109) and SMARCAL1 (OMIM: 606622) of
      humans. Two sets of synthetic MLPA probes for these coding exons were tested.
      Changes in copy numbers were detected as well as single nucleotide polymorphisms
      (SNPs) by complementary DNA sequence analyses. The MLPA method was shown to be
      reliable for mutation detection and identified five published and 12 new
      mutations. In all cases from a Morbus Sandhoff cohort of patients, exclusively
      one variation in copy number was observed and linked to a nucleotide alteration
      called c.1614-14C>A. This deletion comprised exons 1-5. One of these cases is
      described in detail. Deletions were neither detected in the GM2A nor the SMARCAL1
      genes. The MLPA assays complement routine diagnostics for M. Sandhoff (OMIM:
      268800), M. Tay-Sachs variant AB (OMIM: 272750) and Schimke immuno-osseous
      dysplasia (OMIM: 242900).

PMID- 23010211
TI  - Succinate production by metabolically engineered Escherichia coli using sugarcane
      bagasse hydrolysate as the carbon source.
AB  - Efficient biosynthesis of succinate from a renewable biomass resource by
      engineered Escherichia coli is reported in this paper. Fermentation of sugarcane
      bagasse hydrolysate by engineered E. coli BA204, a pflB, ldhA, and ppc deletion
      strain overexpressing the ATP-forming phosphoenolpyruvate carboxykinase from
      Bacillus subtilis 168, produced a final succinate concentration of 15.85 g L(-1)
      with a high yield of 0.89 g L(-1) total sugar under anaerobic conditions. During
      dual-phase fermentations, initial aerobic growth facilitated subsequent anaerobic
      succinate production, with a final succinate concentration of 18.88 g L(-1) and a
      yield of 0.96 g g(-1) total sugar after 24 h of anaerobic fermentation. The high
      succinate yield from sugarcane bagasse hydrolysate demonstrated a great potential
      application of renewable biomass as a feedstock for the economical production of
      succinate using metabolically engineered E. coli.

PMID- 23010212
TI  - Optimization of ethanol production from carob pod extract using immobilized
      Saccharomyces cerevisiae cells in a stirred tank bioreactor.
AB  - In this study, optimization of ethanol production from carob pod extract was
      carried out by immobilized Saccharomyces cerevisiae. Results showed that Ca
      alginate concentration and the amount of immobilized cells had significant
      effects on yield. Optimum conditions for ethanol fermentation were determined to
      be 2% Ca-alginate concentration, 150 rpm agitation rate, 5% yeast cells entrapped
      in beads and pH 5.5. After validation experiments; ethanol concentration, yield,
      production rate and sugar utilization rate were respectively 40.10 g/L, 46.32%,
      3.19 g/L/h and 90.66%; and the fermentation time was decreased to 24 h. In
      addition, the immobilized cells were shown to be reusable for five cycles, though
      a decrease in yield was observed. Finally, carob pod extract was used for ethanol
      fermentation by controlled and uncontrolled pH without any enrichment, and the
      results suggest that carob extract can be utilized effectively by immobilized
      cell fermentation without the use of enrichments to facilitate yeast growth.

PMID- 23010213
TI  - Influence of organic matter generated by Chlorella vulgaris on five different
      modes of flocculation.
AB  - Microalgae excrete relatively large amounts of algal organic matter (AOM) that
      may interfere with flocculation. The influence of AOM on flocculation of
      Chlorella vulgaris was studied using five different flocculation methods:
      aluminum sulfate, chitosan, cationic starch, pH-induced flocculation and electro
      coagulation-flocculation (ECF). The presence of AOM was found to inhibit
      flocculation for all flocculation methods resulting in an increase of dosage
      demand. For pH-induced flocculation, the dosage required to achieve 85%
      flocculation increased only 2-fold when AOM was present, while for chitosan, this
      dosage increased 9-fold. For alum, ECF and cationic starch flocculation, the
      dosage increased 5-6-fold. Interference by AOM is an important parameter to
      consider in the assessment of flocculation-based harvesting of microalgae.

PMID- 23010214
TI  - An integrated approach for Cr(VI)-detoxification with polyaniline/cellulose fiber
      composite prepared using hydrogen peroxide as oxidant.
AB  - In this short communication, the demonstration of a new integrated process
      concept involving the use of a bio-based material for detoxification of Cr(VI)
      contaminated water is presented. Specifically, the bio-based material is a
      polyaniline/cellulose fiber composite prepared by in situ polymerization of
      aniline in the presence of cellulose fibers, using the industrially favorable
      hydrogen peroxide (instead of costly oxidants such as ammonium persulfate) as the
      oxidant. Ferric chloride was used to catalyze the polymerization reaction. The
      process conditions for the preparation of the composite were preliminarily
      optimized, and the proposed concept was demonstrated. Under the conditions
      studied, the use of the composite was quite effective in the detoxification of
      the model solution. The proposed concept may serve as an alternative approach for
      water treatment using renewable materials.

PMID- 23010215
TI  - One-step fermentation of pretreated rice straw producing microbial oil by a novel
      strain of Mortierella elongata PFY.
AB  - A fungus strain producing microbial oils utilizing pretreated rice straw was
      isolated from soil. This strain was identified as Mortierella elongata PFY based
      on the morphology and internal transcribed spacer sequence. Using pretreated rice
      straw as substrate, the average yield of total lipids was 7.07% after 7 days
      fermentation. The GC-MS detection demonstrated that the lipids were composed of
      saturated fatty acids and polyunsaturated fatty acids. This work presents one new
      way to make the waste biomass (rice straw) valuable.

PMID- 23010216
TI  - Effects of pH and dissolved CO2 level on simultaneous production of 2,3
      butanediol and succinic acid using Klebsiella pneumoniae.
AB  - The influences of pH and dissolved CO2 level on the regulation of growth and
      formation of catabolic end products have been investigated in Klebsiella
      pneumoniae. With increasing CO2 levels, there were no apparent changes in 2,3
      butanediol production but succinic acid productions were enhanced significantly.
      A novel strategy for co-production of 2,3-butanediol and succinic acid using K.
      pneumoniae was developed by controlling pH and dissolved CO2 concentration in
      fermentation medium. Under the optimum condition, maximal 77.1 g l(-1) 2,3
      butanediol and 28.7 g l(-1) succinic acid were obtained after 60 h of fed-batch
      fermentation, giving a 2,3-butanediol+succinic acid yield of 1.03 mol mol(-1)
      glucose. This type of fermentation producing two commercial interests at the same
      fermentation process might be considered for a promising biological production
      process which will decrease the production cost by sharing the operation and
      recovery cost.

PMID- 23010217
TI  - Probiotic Lactobacillus reuteri strains ATCC PTA 5289 and ATCC 55730 differ in
      their cariogenic properties in vitro.
AB  - OBJECTIVE: The effects of probiotics on cariogenic biofilms remain controversial.
      Our aim was to characterise two probiotic Lactobacillus reuteri strains, ATCC PTA
      5289 and ATCC 55730 from a cariogenic standpoint in vitro. These strains are used
      in commercial products designed for oral health purposes. DESIGN: The adhesion
      and biofilm formation were studied on saliva-coated hydroxyapatite. The effects
      of glucose or sucrose on the biofilm formation were also tested. Arginine
      metabolism was assessed by measuring the pH in the presence of glucose and
      arginine. The degradation of hydroxyapatite was measured in three different
      growth media. Streptococcus mutans strains Ingbritt and MT 8148 were used as
      positive controls for bacterial adhesion and degradation of hydroxyapatite.
      RESULTS: Strain ATCC PTA 5289 adhered on saliva-coated hydroxyapatite and formed
      detectable biofilm, but strain ATCC 55730 was poor in both adhesion and biofilm
      formation. Both strains were arginolytic and raised the pH in the presence of
      arginine. The amount of dissolved calcium from hydroxyapatite correlated with
      bacterial growth rate and the final pH of the growth medium. CONCLUSION: L.
      reuteri strains ATCC PTA 5289 and ATCC 55730 differed in their adhesion, biofilm
      formation and arginine metabolism in vitro. Thus, these probiotic lactobacilli
      are likely to differ in their behaviour and cariogenic potential also in an oral
      environment.

PMID- 23010218
TI  - Particle-cell dynamics in human blood flow: implications for vascular-targeted
      drug delivery.
AB  - The outcome of vascular-targeted therapies is generally determined by how
      efficiently vascular-targeted carriers localize and adhere to the endothelial
      wall at the targeted site. This study investigates the impact of leukocytes,
      platelets and red blood cells on the margination of vascular-targeted polymeric
      nanospheres and microspheres under various physiological blood flow conditions.
      We report that red blood cells either promote or hinder particle adhesion to an
      endothelial wall in a parallel plate flow chamber depending on the blood flow
      pattern, hematocrit, and particle size. Leukocytes prevent microspheres - but not
      nanospheres - from adhering in laminar and pulsatile flows via (1) competition
      for the available binding space and (2) physical removal of previously bound
      spheres. In recirculating blood flow, the negative effect of leukocytes on
      particle adhesion is minimal for large microspheres in the disturbed flow region
      beyond the flow reattachment. Resting platelets were found to have no effect on
      particle binding likely due to their dimensions and minimal interaction with the
      endothelial wall. Overall, the findings of the present work would be critical for
      designing effective vascular-targeted carriers for imaging and drug delivery
      applications in several human diseases.

PMID- 23010219
TI  - Human head-neck computational model for assessing blast injury.
AB  - A human head finite element model (HHFEM) was developed to study the effects of a
      blast to the head. To study both the kinetic and kinematic effects of a blast
      wave, the HHFEM was attached to a finite element model of a Hybrid III ATD neck.
      A physical human head surrogate model (HSHM) was developed from solid model files
      of the HHFEM, which was then attached to a physical Hybrid III ATD neck and
      exposed to shock tube overpressures. This allowed direct comparison between the
      HSHM and HHFEM. To develop the temporal and spatial pressures on the HHFEM that
      would simulate loading to the HSHM, a computational fluid dynamics (CFD) model of
      the HHFEM in front of a shock tube was generated. CFD simulations were made using
      loads equivalent to those seen in experimental studies of the HSHM for shock tube
      driver pressures of 517, 690 and 862 kPa. Using the selected brain material
      properties, the peak intracranial pressures, temporal and spatial histories of
      relative brain-skull displacements and the peak relative brain-skull
      displacements in the brain of the HHFEM compared favorably with results from the
      HSHM. The HSHM sensors measured the rotations of local areas of the brain as well
      as displacements, and the rotations of the sensors in the sagittal plane of the
      HSHM were, in general, correctly predicted from the HHFEM. Peak intracranial
      pressures were between 70 and 120 kPa, while the peak relative brain-skull
      displacements were between 0.5 and 3.0mm.

PMID- 23010220
TI  - Immunological evaluation of Vibrio alginolyticus, Vibrio harveyi, Vibrio
      vulnificus and infectious spleen and kidney necrosis virus (ISKNV) combined
      vaccine efficacy in Epinephelus coioides.
AB  - Combined vaccines are immunological products intended for immunization against
      multifactorial infectious diseases caused by different types or variants of
      pathogens. In this study, the effectiveness of Vibrio alginolyticus (Va), Vibrio
      harveyi (Vh), Vibrio vulnificus (Vv) and infectious spleen and kidney necrosis
      virus (ISKNV), an iridovirus, combined-vaccine (Vibrio and ISKNV combined
      vaccines, VICV), Va+Vh+Vv inactive vaccine (VIV) and ISKNV whole cell inactive
      vaccine (IWCIV) in Epinephelus coioides were evaluated using various
      immunological parameters including antibody titer, serum lysozyme activity (LA),
      respiratory burst (RB) activity, bactericidal activity (BA) and relative
      percentage survival (RPS). E. coioides immunized with VICV and challenged with
      Va+Vh+Vv+ISKNV had an RPS of 80%. The RPS was 73.3% in E. coioides immunized with
      VIV and challenged with Va+Vh+Vv. E. coioides immunized with IWCIV and challenged
      with ISKNV had an RPS of 69.6%. Serum LA in the vaccinated group was
      significantly higher than the control group on days 21 and 28 post-vaccination
      (P<0.01). The RB activity of head kidney cells in the vaccinated group was
      significantly higher (P<0.01) compared to that in the control group. However, RB
      activity of spleen cells in the vaccinated group and the control group were not
      significantly different (P>0.05). After immunization with VICV, BA values of
      blood leucocytes and head kidney cells increased significantly more than spleen
      cells. BA value of blood leucocytes was higher than that in head kidney cells.
      There were distinct difference between BA values in head kidney cells and in
      spleen cells (P<0.05) as well as between BA value of blood leucocytes and head
      kidney cells (P<0.01). E. coioides vaccinated with VICV have significantly higher
      antibody levels than control groupers (P<0.01). Our study suggests that the VICV
      candidate can effectively protect groupers against multiple bacterial and viral
      pathogens.

PMID- 23010221
TI  - Evaluation of cell-mediated immune responses against porcine circovirus type 2
      (PCV2) Cap and Rep proteins after vaccination with a commercial PCV2 sub-unit
      vaccine.
AB  - This study investigated the development of cellular immunity to Porcine
      circovirus type 2 (PCV2) Cap and Rep proteins in pigs vaccinated with a
      commercial PCV2 genotype a (PCV2a) based sub-unit vaccine, before and after a
      heterologous challenge with a PCV2b isolate. At three weeks of age, 20 pigs were
      inoculated intramuscularly with either the vaccine product (V group, n=9) or
      phosphate buffered saline solution (PBS) (NV group, n=11). Three weeks after
      vaccination, pigs were challenged intranasally with PCV2b (V-C and NV-C groups)
      or PBS (V-NC and NV-NC groups). None of the pigs developed clinical signs during
      the whole experiment, but all NV-C and 3/5 V-C pigs developed viraemia.
      Vaccination induced the development IFN-gamma-secreting cells in response to the
      Cap protein of PCV2, which appeared three weeks post-vaccination and increased
      after challenge. By that time, no significant differences were detected on PCV2
      antibody titres between vaccinated and non-vaccinated pigs, although there were
      significant differences on day 7 post-challenge. PCV2-inoculation induced a
      cellular response against the Rep protein. Such response was significantly
      reduced or even absent in PCV2-inoculated pigs that were previously vaccinated (V
      C group), presumably as a result of a lower PCV2 replication in vaccinated
      animals compared to non-vaccinated ones.

PMID- 23010222
TI  - Mechanisms for epigallocatechin gallate induced inhibition of drug metabolizing
      enzymes in rat liver microsomes.
AB  - Epigallocatechin gallate (EGCG) inhibits drug metabolizing enzymes by unknown
      mechanisms. Here we examined if the inhibition is due to covalent-binding of EGCG
      to the enzymes or formation of protein aggregates. EGCG was incubated with rat
      liver microsomes at 1-100MUM for 30min. The EGCG-binding proteins were affinity
      purified using m-aminophenylboronic acid agarose and probed with antibodies
      against glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin, cytochrome P450
      (CYP) 1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP3A, catechol-O-methyltransferase (COMT)
      and microsomal glutathione transferase 1 (MGST1). All but actin and soluble COMT
      were positively detected at >=1MUM EGCG, indicating EGCG selectively bound to a
      subset of proteins including membrane-bound COMT. The binding correlated well
      with inhibition of CYP activities, except for CYP2E1 whose activity was
      unaffected despite evident binding. The antioxidant enzyme MGST1, but not
      cytosolic GSTs, was remarkably inhibited, providing novel evidence supporting the
      pro-oxidative effects of EGCG. When microsomes incubated with EGCG were probed on
      Western blots, all but the actin and CYP2E1 antibodies showed a significant
      reduction in binding at >=1MUM EGCG, suggesting that a fraction of the indicated
      proteins formed aggregates that likely contributed to the inhibitory effects of
      EGCG but were not recognizable by antibodies against the intact proteins. This
      raised the possibility that previous reports on EGCG regulating protein
      expression using GAPDH as a reference should be revisited for accuracy.
      Remarkable protein aggregate formation in EGCG-treated microsomes was also
      observed by analyzing Coomassie Blue-stained SDS-PAGE gels. EGCG effects were
      partially abolished in the presence of 1mM glutathione, suggesting they are
      particularly relevant to the in vivo conditions when glutathione is depleted by
      toxicant insults.

PMID- 23010223
TI  - Chronic exposure to sulfur dioxide enhances airway hyperresponsiveness only in
      ovalbumin-sensitized rats.
AB  - Sulfur dioxide (SO(2)) is a common air pollutant that triggers asthmatic
      symptoms, but its toxicological mechanisms are not fully understood.
      Specifically, it is unclear how airborne SO(2) affects airway hyperresponsiveness
      (AHR) - a hallmark feature of asthma. To this end, we investigated the effects of
      chronic exposure to SO(2) on AHR, airway inflammation, tissue remodeling, cell
      stiffness (G') and contractility of the airway smooth muscle cell (ASMC). Newborn
      Sprague-Dawley (SD) rats sensitized to ovalbumin (OVA) was used as the model to
      mimic asthmatic symptoms. The experimental results show that exposure to SO(2):
      (1) significantly increased Penh (an indicator of AHR) in the OVA-sensitized rats
      (p<0.01) but not in the normal rats (p>0.05), which correlated with the increase
      of airway smooth muscle mass; (2) increased IL-4 production in BALF of both the
      normal (p<0.05) and OVA-sensitized rats (p<0.001), but decreased IFN-gamma in
      BALF of only the normal rats, and in serum only increased IL-4 production of the
      OVA-sensitized rats (p<0.001); (3) increased ASMC stiffness (G') and
      contractility only in the OVA-sensitized rats (p<0.001, p<0.05, respectively).
      Taken together, these results demonstrate that SO(2) may be a universal airway
      inflammatory factor, but more importantly, specific to exacerbating AHR in
      asthmatics only. These findings uncover a potential mechanism of SO(2)-induced
      health effects and may provide a basis for therapeutic targets.

PMID- 23010224
TI  - Dietary intake of PCDD/Fs and dioxin-like PCBs from the Chinese total diet study
      in 2007.
AB  - Concentrations of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) and 12 dioxin-like polychlorinated biphenyls (dl-PCBs) were measured in
      96 food composite samples from eight varieties of food groups from the Chinese
      total diet study (TDS) in 2007. The concentrations of samples, expressed as WHO
      toxic equivalents (TEQ), ranged from 0.001 pg TEQ g(-1) to 0.85 pg TEQ g(-1)
      (fresh weight). Dietary intake of PCDD/Fs and dl-PCBs of 12 age/gender subgroups
      of the Chinese population subsequently estimated ranges from 15.4 pg TEQ kg(-1)
      bw month(-1) to 38.7 pg TEQ kg(-1) bw month(-1) for average population and from
      68.5 pg TEQ kg(-1) bw month(-1) to 226.1 pg TEQ kg(-1) bw month(-1) for high
      consumers (the 97.5th percentile). Dietary exposure of children (mean: 32.5 pg
      TEQ kg(-1) bw month(-1)) is significantly higher than that of the adults (mean:
      21.5 pg TEQ kg(-1) bw month(-1)) (p<0.01) presumably due to more food consumed by
      children relative to their body weight compared to adults. There is no difference
      of dietary exposure, expressed as pg TEQ kg(-1) bw, found between different
      genders. Across various regions in China, there are large differences of dietary
      exposure of adult population and pattern of contribution of food groups to total
      exposure due to different contamination level and food habits. Dietary exposures
      of average population of various subgroups were all below the PTMI recommended by
      JECFA, but those of higher consumers were found exceeding or comparable to the
      PTMI.

PMID- 23010225
TI  - In vitro opsonin-independent interactions between cells of smooth and rough
      phenotypes of Flavobacterium psychrophilum and rainbow trout (Oncorhynchus
      mykiss) head kidney macrophages.
AB  - The cytotoxic activity of smooth and rough phenotypic cells of the fish
      pathogenic Gram-negative bacterium Flavobacterium psychrophilum to rainbow trout
      (Oncorhynchus mykiss) head kidney macrophages was investigated in vitro. The
      cytotoxicity to macrophages was significantly higher for rough cells compared
      with the smooth cells. The cytotoxic activity increased for both cell types with
      increasing temperature and the cells retained their cytotoxic nature after
      metabolical inactivation by heat, suggesting a cell-bound cytotoxic mechanism.
      The cytotoxicity was significantly reduced in both cell types after treatment
      with sodium (meta)periodate, indicating that the major bacterial structure
      involved in the cytotoxicity is of carbohydrate nature. Trypsin treatment further
      reduced the cytotoxicity in smooth cells, while sialic acid treatment reduced the
      cytotoxicity in rough cells, suggesting different lysing mechanisms for the two
      phenotypic variants. The results from the present study therefore suggest that
      the cytotoxic activity of F. psychrophilum to rainbow trout macrophages in vitro
      is stronger expressed in the rough phenotype and that it is opsonin-independent
      and initiated by binding of bacterial surface carbohydrates to lectins on the
      surface of the macrophages. How the lysis of the macrophages is executed is still
      unclear but it is suggested to function by different mechanisms in the smooth and
      the rough cells. The migration of rainbow trout macrophages toward smooth and
      rough cells of F. psychrophilum was further investigated. The results show that
      the macrophages were able to recognize both cell types, but the migration rate
      did not differ between the two phenotypes.

PMID- 23010226
TI  - Th1/Th17 cells in organic dust-induced airway disease.

PMID- 23010227
TI  - Evaluation of paradoxical vocal fold motion.

PMID- 23010228
TI  - Effect of depressive symptoms on asthma intervention in urban teens.
AB  - BACKGROUND: The literature suggests that depression is an important comorbidity
      in asthma that can significantly influence disease management and quality of life
      (QOL). OBJECTIVE: To study the effect of coexisting depressive symptoms on the
      effectiveness of self-management interventions in urban teens with asthma.
      METHODS: We analyzed data from a randomized controlled trial of Puff City, a web
      based, tailored asthma management intervention for urban teens, to determine
      whether depression modulated intervention effectiveness for asthma control and
      QOL outcomes. Teens and caregivers were classified as depressed based on
      responses collected from baseline questionnaires. RESULT: Using logistic
      regression analysis, we found that a lower percentage of treatment students had
      indicators of uncontrolled asthma compared with controls (adjusted odds ratios
      <1). However, for teens depressed at baseline, QOL scores at follow-up were
      significantly higher in the treatment group compared with the control group for
      the emotions domain (adjusted relative risk, 2.08; 95% confidence interval, 1.2
      3.63; P = .01; interpreted as emotional QOL for treatment students increased by a
      factor of 2.08 above controls). Estimates for overall QOL and symptoms QOL were
      borderline significant (adjusted relative risk, 1.57; 95% confidence interval,
      0.93-2.63; P = .09; and adjusted relative risk, 1.72; 95% confidence interval,
      0.94-3.15; P = .08; respectively). Among teens not depressed at baseline, no
      significant differences were observed between treatment and control groups in QOL
      domains at follow-up. CONCLUSION: Our results suggest that depression modified
      the relationship between the effectiveness of an asthma intervention and
      emotional QOL in urban teens. Further assessment of self-management behavioral
      interventions for asthma should explore the mechanism by which depression may
      alter the intervention effect.

PMID- 23010229
TI  - Association between obesity and asthma in the elderly population: potential roles
      of abdominal subcutaneous adiposity and sarcopenia.
AB  - BACKGROUND: Obesity is a significant risk factor for asthma; however, the
      association of asthma with obesity has rarely been studied in the elderly
      population. The role of central obesity has been suggested as a link between the
      2 entities but has not been comprehensively studied in elderly populations.
      OBJECTIVE: To investigate the mechanisms of association between obesity and
      asthma in the elderly population. METHODS: This cross-sectional analysis included
      994 participants (aged >=65 years) in the Korean Longitudinal Study on Health and
      Aging. Asthma was defined by using questionnaires. Spirometry and chest
      radiography were performed to exclude asthma-mimicking conditions. Measurements
      of abdominal subcutaneous and visceral fat were calculated by computed tomography
      of the abdomen, and regional body compositions were measured by dual energy X-ray
      absorptiometry. Biochemical parameters were also measured. RESULTS: The
      prevalence of asthma was 5.4%. The study population had a mean body mass index
      (BMI) of 24.0. Multivariate logistic regression tests revealed that the risk of
      asthma increased in proportion to an increase in BMI or abdominal subcutaneous
      adiposity. However, no association was found with visceral adiposity, serum
      adiponectin levels, or serum vitamin D levels. The dual energy X-ray
      absorptiometry-measured appendicular fat-free mass index was inversely related to
      asthma among patients with a BMI of 25.0 or greater. CONCLUSION: Our findings
      suggest that the relationships between obesity and asthma in the elderly
      population may be mediated by factors such as abdominal subcutaneous adiposity
      and sarcopenia. These associations warrant further investigations to identify
      their potential roles.

PMID- 23010231
TI  - Factors contributing to risks for pediatric asthma in rural Saskatchewan.
AB  - BACKGROUND: Rural children have lower reported rates of asthma compared with
      urban children. Although reasons for these differences remain unclear, 3 possible
      explanations exist: (1) environmental differences, (2) variations in health care
      access, and (3) variations in health risk behaviors. OBJECTIVE: We investigated
      asthma among children living on farms and in small towns and its potential
      determinants, including personal, behavioral, and environmental factors. METHODS:
      School children (n = 842, ages 6-13; participation rate = 72.0%) were involved in
      a 2003 cross-sectional study. Their parents completed a lung health survey that
      included questions about asthma, asthma-like symptoms, and potential determinants
      of asthma (demographic, environmental, health risk behaviors). Participating
      children were classified into farm dwellers (live on farm or acreage) and small
      town dwellers. Multiple logistic regression was used to investigate the
      association between asthma and wheeze with demographic, environmental, and
      behavioral exposures with simultaneous adjustment for confounders. RESULTS:
      Asthma and wheeze prevalence was not significantly different between farm and
      small town areas (current asthma: 16% vs 13%, respectively; current wheeze: 27%
      vs 21%, respectively) and followed consistent patterns. Factors associated with
      diagnosed asthma were dampness (odds ratio [OR] = 1.85; 95% confidence interval
      [CI] = 1.08-3.17), with enrollment in daycare found to be protective (OR = 0.53;
      95% CI = 0.33-0.85). Being obese or overweight was associated with wheeze (OR =
      1.77; 95% CI = 1.06-2.97). CONCLUSION: Given the differences between areas and
      the associations between environmental risk factors and obesity with asthma and
      wheeze, the study findings support environment and health risk behavior
      explanations for the observed geographic variations.

PMID- 23010230
TI  - Repeated exposure to polycyclic aromatic hydrocarbons and asthma: effect of
      seroatopy.
AB  - BACKGROUND: Exposure to traffic-related air pollutants, including polycyclic
      aromatic hydrocarbons (PAHs), can induce asthma. However, the effects of early
      repeated PAH exposure over time on different asthma phenotypes have not been
      examined. OBJECTIVE: To assess associations between repeated PAH exposure,
      measured from prenatal personal and residential indoor monitors in children's
      homes, and asthma in an inner-city cohort. METHODS: Prenatal exposure was
      assessed by personal air monitoring during 48 hours and exposure at 5 to 6 years
      of age by 2-week residential monitoring in the Columbia Center for Children's
      Environmental Health cohort. PAH was dichotomized into pyrene (representative
      semivolatile PAH) and the sum of 8 nonvolatile PAHs. High exposure to each was
      defined as measures above the median at both repeated time points. Asthma and
      wheeze were determined by validated questionnaires at ages 5 to 6 years. Children
      with specific IgE levels greater than 0.35 IU/mL to any of 5 indoor allergens
      were considered seroatopic. RESULTS: Among all 354 children, repeated high
      exposure to pyrene was associated with asthma (odds ratio [OR], 1.90; 95%
      confidence interval [CI], 1.13-3.20). Among 242 nonatopic children, but not those
      sensitized to indoor allergens (n = 87) or with elevated total IgE levels (n =
      171), high pyrene levels were associated positively with asthma (OR, 2.89; 95%
      CI, 1.77-5.69), asthma medication use (OR, 2.28; 95% CI, 1.13-4.59), and
      emergency department visits for asthma (OR, 2.43; 95% CI, 1.20-4.91).
      Associations between the levels of the 8 nonvolatile PAHs and asthma were not
      observed, even when stratifying by seroatopy. CONCLUSION: Nonatopic children may
      be more susceptible to the respiratory consequences of early pyrene exposures.

PMID- 23010232
TI  - Associations of patient outcomes with level of asthma control.
AB  - BACKGROUND: Despite effective medications, asthma remains a significant burden to
      the US health care system. OBJECTIVE: To determine whether partly and
      uncontrolled asthma in respondents to the Asthma Insights and Management (AIM)
      survey was associated with adverse outcomes (such as visits to health care
      professionals and medication use) compared with well-controlled asthma. METHODS:
      The AIM survey, conducted in 2009, included 2,500 patients with asthma who were
      12 years or older. We classified patients into levels of control and compared use
      of health care services and limitations of activities in patients whose asthma
      was well controlled vs those with partly and uncontrolled asthma. RESULTS:
      Patients who reported lower income and educational status and lacked health
      insurance were less likely to have had well-controlled asthma. Respondents with
      uncontrolled asthma were more likely to report ever use of oral steroids (odds
      ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.2) and over-the-counter
      medicine (OR, 2.7; 95% CI, 2.0-3.7) compared with patients whose asthma was well
      controlled. Respondents with partly and uncontrolled asthma were also
      significantly more likely to report ever visiting physicians, specialists, or the
      emergency department or being hospitalized for asthma compared with those whose
      asthma was well controlled (ORs ranging from 2.1 to 5.6). Finally, respondents
      whose asthma was uncontrolled had increased odds (ORs ranging from 14 to 34) of
      reporting that asthma limited their activities compared with respondents whose
      asthma was well controlled. CONCLUSION: Patients with partly and uncontrolled
      asthma defined by international guidelines reported use of significantly more
      health care resources and greater limitations of their daily activities compared
      with patients whose asthma was well controlled.

PMID- 23010234
TI  - Comparison of the long-term efficacy of 3- and 5-year house dust mite allergen
      immunotherapy.
AB  - BACKGROUND: The recommended duration of specific immunotherapy (SIT) treatment
      relies on empiric data and is not well documented. OBJECTIVE: To detect possible
      differences in the long-term effectiveness between 3 and 5 years of house dust
      mite (HDM) SIT in asthmatic children. METHODS: We performed a 3-year natural
      history study of 90 asthmatic children who were sensitive only to HDM. Three
      groups were recruited: 30 who had completed 3 years of HDM SIT (SIT3), 30 who had
      completed 5 years of HDM SIT (SIT5), and 30 who had an indication for HDM SIT but
      whose parents refused HDM SIT. Patients attended an enrollment visit in 2007,
      after SIT discontinuation, and 3 annual follow-up visits at the clinic. The long
      term effectiveness of HDM SIT was primarily assessed via analysis of the
      reduction in required inhaled corticosteroid dose, forced expiratory volume in 1
      second, and asthma remission. RESULTS: A total of 84 children completed the
      study. Both SIT durations produced excellent results; asthma remission in both
      SIT3 (50%) and SIT5 (54%) groups was significantly higher when compared with
      control (3.3%). The minimal controlling inhaled corticosteroid dose reduction in
      SIT5 group (median, 75%) was significantly higher compared with the SIT3 group
      (median, 50%) after immunotherapy discontinuation; after 3 years without SIT, no
      differences were found between the SIT5 and SIT3 groups (median, 100% and 94%,
      respectively). We observed a slightly higher increase in forced expiratory volume
      in 1 second in the SIT5 group compared with the SIT3 group. CONCLUSION: Three
      years of SIT is an adequate duration for the treatment of childhood asthma
      associated with HDM allergy because 2 further years of SIT added no clinical
      benefit.

PMID- 23010233
TI  - alphabeta T cells and a mixed Th1/Th17 response are important in organic dust
      induced airway disease.
AB  - BACKGROUND: Organic dust exposure in agricultural environments induces an
      inflammatory response that attenuates over time, yet repetitive dust exposures
      result in chronic lung diseases. Animal models resembling this chronic lung
      inflammatory response have been developed, yet the underlying cellular mechanisms
      are not well defined. OBJECTIVE: Because mice repetitively exposed to organic
      dust extracts (DE) display increased CD3+ T cell lung infiltrates, we sought to
      determine the phenotype and importance of these cells. METHODS: Mice received
      swine confinement DE repetitively for 3 weeks by established intranasal
      inhalation protocol. Studies were conducted with peptidoglycan (PGN) because it
      is a major DE component in large animal farming environments and has shared
      similar biologic effects with DE. Enumeration of T cells and intracellular
      cytokine profiles were conducted by flow cytometry techniques. Whole lung
      homogenate cytokines were analyzed by multiplex immunoassay. T cell receptor
      (TCR) alphabeta knockouts were used to determine the functional importance of
      alphabeta-expressing T cells. RESULTS: DE increased lung-associated CD3+CD4+ T
      cells and interleukin (IL)-17 (but not IL-4, interferon [IFN]-gamma, IL-10)
      producing CD4+ T cells. PGN treatment resulted in increased IL-17 and IFN-gamma
      producing CD4+ T cells and IFN-gamma producing CD8+ T cells. Both DE and PGN
      augmented expression of cytokines associated with Th1 and Th17 polarization in
      lung homogenates. DE-induced lung mononuclear aggregates and bronchiolar
      compartment inflammation were significantly reduced in TCR knockout animals;
      however, neutrophil influx and alveolar compartment inflammation were not
      affected. CONCLUSION: Studies demonstrated that DE and PGN exposure promote a
      Th1/Th17 lung microenvironment and that alphabeta-expressing T cells are
      important in mediating DE-induced lung pathologic conditions.

PMID- 23010235
TI  - Anaphylaxis secondary to contact with a vomited food allergen.

PMID- 23010236
TI  - Vancomycin-induced DRESS with evidence of T-cell activation in a 22-month-old
      patient.

PMID- 23010237
TI  - Successful treatment of exercise-induced anaphylaxis with omalizumab.

PMID- 23010238
TI  - Exercise-induced hyperventilation: more common than appreciated.

PMID- 23010240
TI  - Allergen of the month--European aspen.

PMID- 23010239
TI  - Successful sirolimus graded dose challenge in an erythromycin-allergic patient.

PMID- 23010241
TI  - Pharmacological characterization of the heartbeat in an extant vertebrate
      ancestor, the Pacific hagfish, Eptatretus stoutii.
AB  - Pharmacological ion-channel blockers were used to investigate the spontaneous
      heart rates in Pacific hagfish, Eptatretus stoutii. Zatebradine, a
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, vastly
      reduced atrial and ventricular contraction rates in a similar concentration
      dependent manner, indicating a major role for HCN in setting intrinsic heart
      rate. When voltage-gated Na(+) channels were blocked with tetrodotoxin (TTX),
      atrial contraction rate declined in a dose-dependent manner, but remained faster
      than ventricular rate even at very high TTX concentrations. This TTX resistance
      compared with other fish suggests an important role for a TTX-sensitive
      inactivation-resistant Na(+) current in atrioventricular conduction and chamber
      synchrony, and a lesser role in setting intrinsic heart rate. T and L-type
      calcium channel blockers, nickel and nifedipine respectively, also reduced atrial
      and ventricular contraction rates, nickel having a larger effect on the atrium.
      These novel results for hagfish are consistent with intrinsic atrial and
      ventricular rates being set mostly by HCN, with lesser contributions from other
      ion channels. We suggest that future electrophysiological studies will reveal
      that hagfishes, with their ancestral position in the evolution of the vertebrate
      type chambered heart, share some but not all features of vertebrate intrinsic
      heart rate control.

PMID- 23010242
TI  - Cortisol promotes differentiation of epidermal ionocytes through Foxi3
      transcription factors in zebrafish (Danio rerio).
AB  - Glucocorticoid regulates epidermal cell proliferation, and is used to treat
      certain skin disorders. Cortisol, a glucocorticoid, is also linked to skin
      development in teleost fish. Cortisol increases the number of epithelial
      ionocytes during environmental acclimation in euryhaline fishes, but it is
      unclear whether this is due to increased differentiation or proliferation. To
      investigate, we treated zebrafish embryos with exogenous cortisol (20mg/L). The
      densities of the ionocytes Na(+)-K(+)-ATPase rich cells (NaRCs) and H(+)-ATPase
      rich cells (HRCs) were significantly increased by cortisol, and this was
      accompanied by an increase in the respective marker genes. Expression of the
      glucocorticoid receptor (GR) gene was decreased. Cortisol treatment also
      increased ionocytes in cultured adult zebrafish gills, and up-regulated
      expression of genes encoding forkhead box I3 (foxi3a and foxi3b) transcription
      factors, which regulate ionocyte progenitor development. GR expression was up
      regulated by cortisol in vitro; as such, the observed decrease in vivo reflects a
      regulatory systemic-negative feedback. Notably, in situ hybridization revealed
      that foxi3a/b mRNA expression was increased by cortisol at 24-48h post
      fertilization. Cortisol also decreased keratinocytes, but did not affect
      epidermal stem cells or mucus cells. We conclude that foxi3a/b transactivation by
      cortisol-GR favors differentiation of ionocyte progenitors, thereby facilitating
      proliferation of mature ionocytes.

PMID- 23010243
TI  - Response of hepatic lipid and glucose metabolism to a mixture or single fatty
      acids: Possible presence of fatty acid-sensing mechanisms.
AB  - To assess the hypothesis that an acute dietary fatty acid (FA) supply may improve
      glucose tolerance in rainbow trout, we orally administered fish with fish oil
      (FO; 10mL.kg(-1), one time), which were then subjected to a glucose tolerance
      test and sampled 6h after injection. Parameters related to glucose and lipid
      metabolism were then assessed. The results suggest that when both nutrients were
      administered at the same time, an increased potential for lipogenesis occurred
      concomitantly with a lower level of glycaemia. In a second experiment we
      administered intraperitoneally a single FA present in the FO mixture such as
      oleic acid (60 or 300MUg.kg(-1)) whereas octanoic acid (60 or 300MUg.kg(-1)) was
      used as negative control (absent from the FO). However, the effects of both FA
      were similar in reducing the potential of lipid synthesis and oxidation, and in
      enhancing the potential of glucose synthesis and glycogenesis. Differences found
      between FO and single FA administration show that response to FA was dependent on
      the treatment (mixture vs. single FA) but also comply with the idea that an
      interaction between FA and glucose rather than FA alone are in the origin of the
      results reported. The administration of individual FA such as oleic and octanoic
      acid failed in enhancing lipogenesis and reducing plasma glucose levels and thus
      in explaining results obtained with FO. However, results provide evidence that FA
      even provided at a low dose play a key role in the regulation of several putative
      components of a FA sensing system present in rainbow trout liver.

PMID- 23010244
TI  - Real-time monitoring of tyrosine hydroxylase activity using a plate reader assay.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting step in dopamine (DA) synthesis,
      oxidizing tyrosine to l-DOPA, which is further metabolized to DA. Current assays
      for monitoring activity of this enzyme require extensive work-up, require long
      analysis time, and measure end points, thereby lacking real-time kinetics. This
      work presents the development of the first real-time colorimetric assay for
      determining the activity of TH using a plate reader. The production of l-DOPA is
      followed using sodium periodate to oxidize l-DOPA to the chromophore dopachrome,
      which can be monitored at 475 nm. Advantages to this method include decreased
      sample analysis time, shorter assay work-up, and the ability to run a large
      number of samples at one time. Furthermore, the assay was adapted for high
      throughput screening and demonstrated an excellent Z-factor (> 0.8), indicating
      suitability of this assay for high-throughput analysis. Overall, this novel assay
      reduces analysis time, increases sample number, and allows for the study of
      activity using real-time kinetics.

PMID- 23010246
TI  - Critical assessment of extraction methods for the simultaneous determination of
      pesticide residues and mycotoxins in fruits, cereals, spices and oil seeds
      employing ultra-high performance liquid chromatography-tandem mass spectrometry.
AB  - This study addresses a current trend in chemical food safety control represented
      by an effort to integrate analyses of various groups of food
      contaminants/toxicants into a single, high-throughput method. The choice of
      optimal sample preparation step is one of the key conditions to achieve good
      performance characteristics. In this context, we investigated the possibility to
      expand the scope of the three multi-analyte extraction procedures employed
      earlier in other studies for rapid isolation of either pesticides or mycotoxins
      from plant matrices. Following procedures were tested: A - aqueous acetonitrile
      extraction followed by partition (QuEChERS-like method), B - aqueous acetonitrile
      extraction, and C - pure acetonitrile extraction. On the list of target analytes,
      we had 288 pesticides (including 'troublesome' acidic, basic and base-sensitive
      compounds) together with 38 mycotoxins (including all EU regulated ones and many
      'emerging' toxins on the European Food Safety Authority (EFSA) list). The
      matrices selected for the experiments, apple baby food, wheat flour, spices and
      sunflower seeds, represented various composition categories in terms of moisture,
      fat and extractable compounds (e.g. pigments and essential oils) content. In
      preliminary experiments, acceptable recoveries (70-120%) for most of analytes
      were obtained by the analysis of spiked matrices, regardless which extraction
      procedure was used. However, when analysing dry samples with incurred pesticide
      residues/mycotoxins, the method C did not enable efficient extraction of some
      common contaminants. Procedure A, thanks to a higher matrix equivalent compared
      to the method B and relatively less pronounced matrix effects, enabled lower
      quantification limits for all analyte/matrix combinations, with the exception of
      polar mycotoxins and/or pesticides. Higher recoveries for the latter group of
      analytes could be achieved by the method B; on the other hand, extraction
      efficiency of non-polar pesticides from fatty matrix was rather poor by this
      method.

PMID- 23010245
TI  - A sequentially Markov conditional sampling distribution for structured
      populations with migration and recombination.
AB  - Conditional sampling distributions (CSDs), sometimes referred to as copying
      models, underlie numerous practical tools in population genomic analyses. Though
      an important application that has received much attention is the inference of
      population structure, the explicit exchange of migrants at specified rates has
      not hitherto been incorporated into the CSD in a principled framework. Recently,
      in the case of a single panmictic population, a sequentially Markov CSD has been
      developed as an accurate, efficient approximation to a principled CSD derived
      from the diffusion process dual to the coalescent with recombination. In this
      paper, the sequentially Markov CSD framework is extended to incorporate
      subdivided population structure, thus providing an efficiently computable CSD
      that admits a genealogical interpretation related to the structured coalescent
      with migration and recombination. As a concrete application, it is demonstrated
      empirically that the CSD developed here can be employed to yield accurate
      estimation of a wide range of migration rates. 

PMID- 23010247
TI  - Validation of a method for the determination of tributyltin in seawater by stir
      bar sorptive extraction-liquid chromatography tandem mass spectrometry.
AB  - The main objective of this work is to develop an accurate, sensitive, simple and
      cost-effective method for the determination of tributyltin species (as cationic
      form) in seawater at ultra-trace levels. The method is based on the use of stir
      bar sorptive extraction (SBSE) followed by solvent desorption and liquid
      chromatography tandem mass spectrometry (SD-LC-MS/MS (QqQ)) analysis, operating
      in positive electrospray ionisation (ESI) and in the selected reaction monitoring
      (SRM) mode. Extraction and LC-MS/MS parameters were accurately optimised to
      achieve the highest recoveries and to enhance the analytical characteristics of
      the method. The different parameters that affect the extraction procedure, the
      chromatographic and spectrometric conditions, and the surrogate selection were
      evaluated. In contrast with previously proposed methods, the proposed method
      involves a simplified sample treatment. Quality parameters such as linearity,
      accuracy in terms of trueness and precision, uncertainty and specificity were
      examined with good results. The evaluation of two surrogates (tri-n-propyltin
      chloride and tripentyltin chloride) was also carried out. The limit of detection
      (LOD) and limit of quantification (LOQ) obtained were 0.8 and 2.5 ngL(-1),
      respectively. Precision, expressed as relative standard deviation (%RSD), was
      lower than 16%, and the determination coefficient (R(2)) was higher than 0.990
      with a residual deviation for each calibration point lower than +/-25%. Mean
      recoveries were between 92% and 102%. The accuracy of the method was also studied
      by participating in an external proficiency testing scheme. After validation, the
      method was applied to the analysis of all tributyltin species found in natural
      seawater samples. The method meets the requirements of the United States
      Environmental Protection Agency (US-EPA).

PMID- 23010248
TI  - Theoretical and experimental impact of the bed aspect ratio on the axial
      dispersion coefficient of columns packed with 2.5 MUm particles.
AB  - The impact of the ratio of the column diameter to the average particle size (or
      bed aspect ratio) on the column performance was investigated from theoretical and
      experimental viewpoints. The experiments were conducted for two series of 100mm
      long columns, 2.1, 3.0, and 4.6mm in diameter, packed with 2.5 MUm fully porous
      particles of Bridge Ethylene Hybrid (BEH) for one series and Charged Surface
      Hybrid (CSH) for the other. The heights equivalent to a theoretical plate (HETP)
      of two low molecular weight compounds, uracil (non-retained, k=0) and naphthalene
      (retained, k=2.5), were determined from the true moments of the recorded peak
      profiles. The results showed a systematic decrease of the column performance for
      uracil at high flow velocities with decreasing column inner diameter, in
      agreement with the theoretical predictions of the variation of the trans-column
      eddy dispersion HETP term with decreasing bed aspect ratio. This result is
      consistent with the increasing volume fraction of the wall region of the column,
      in which the average linear velocity of the mobile phase over a distance of 5
      particle diameters from the column wall is about 10% larger than in the bulk
      center of the column (infinite diameter column). For the retained compound, the
      discrepancies are levelled out due to the longer average residence time and
      larger particle diffusivities of retained compounds, which allow a more efficient
      relaxation of the radial concentration gradients. Further improvements of the
      performance of the larger I.D. columns (3.0 and 4.6mm I.D.) may be achieved by
      decreasing the harmful effect of this trans-column velocity bias by injecting
      and/or collecting the sample molecules in a wide central zone of the column. For
      2.1mm I.D. columns, this approach would prove useful only when HPLC instruments
      providing a lower extra-column band broadening contribution will become
      available. Finally, the further minimization of the trans-column eddy dispersion
      HETP term and the design of new, better inlet/outlet column endfitting/frit
      assemblies requires newer and more accurate models of eddy dispersion in packed
      columns than those previously provided by Gunn and Giddings and the numerical
      calculation of band profiles using original functions to account for the
      distribution and collection of the sample molecules at the inlet and outlet of
      the column.

PMID- 23010249
TI  - Optimization of human serum albumin monoliths for chiral separations and high
      performance affinity chromatography.
AB  - Various organic-based monoliths were prepared and optimized for immobilization of
      the protein human serum albumin (HSA) as a binding agent for chiral separations
      and high-performance affinity chromatography. These monoliths contained co
      polymers based on glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate
      (EDMA) or GMA and trimethylolpropane trimethacrylate (TRIM). A mixture of
      cyclohexanol and 1-dodecanol was used as the porogen, with the ratio of these
      solvents being varied along with the polymerization temperature to generate a
      library of monoliths. These monoliths were used with both the Schiff base and
      epoxy immobilization methods and measured for their final content of HSA.
      Monoliths showing the highest protein content were further evaluated in
      chromatographic studies using R/S-warfarin and d/l-tryptophan as model chiral
      solutes. A 2.6-2.7-fold increase in HSA content was obtained in the final
      monoliths when compared to similar HSA monoliths prepared according to the
      literature. The increased protein content made it possible for the new monoliths
      to provide higher retention and/or two-fold faster separations for the tested
      solutes when using 4.6mm i.d.* 50 mm columns. These monoliths were also used to
      create 4.6mm i.d.* 10 mm HSA microcolumns that could separate the same chiral
      solutes in only 1.5-6.0 min. The approaches used in this study could be extended
      to the separation of other chiral solutes and to the optimization of organic
      monoliths for use with additional proteins as binding agents.

PMID- 23010250
TI  - Bacteriological and molecular detection of Mycobacterium bovis in cattle with
      inconclusive results to intradermal tuberculin tests.
AB  - A dairy herd (77 cows) from Rio de Janeiro, Brazil, with a history of
      tuberculosis infection was tested by a comparative cervical test (CCT). Seventeen
      cows were reactive and seven were inconclusive (swelling >= 2.0 mm and <= 3.9 mm,
      respectively). All of these 24 cows were slaughtered and necropsied ; samples
      from lungs and lymph nodes were collected for multiplex polymerase chain reaction
      (PCR) and culturing. Infection was confirmed in 23/24 (95.8%) of the slaughtered
      animals (five by culturing, four by PCR, and 14 by both tests). All cows with
      inconclusive results at CCT were confirmed as infected. Although slaughter of
      inconclusive reactor cows is not mandatory in many countries, our study provided
      evidence to support the slaughter of these cows, at least during an outbreak.

PMID- 23010251
TI  - The N-terminal glycine-rich and cysteine-rich regions are essential for
      antimicrobial activity of crustinPm1 from the black tiger shrimp Penaeus monodon.
AB  - An antimicrobial protein crustinPm1 from Penaeus monodon is a WAP domain
      containing protein with an antimicrobial activity against Gram-positive bacteria
      but does not have antiproteinase activity. The lack of antiproteinase is
      speculated to be due to the P(1)' Met and/or the length of spacing between the
      conserved Cys2 and Cys3 while the antimicrobial activity may be due to the N
      terminal Gly-rich and Cys-rich regions. In this study, the P(1)-P(1)' and the N
      terminal Gly-rich and Cys-rich regions of crustinPm1 were mutated by amino acid
      substitution or deletion. Substitutions of P(1)-P(1)' from Pro-Pro to Leu-Leu,
      Leu-His, Leu-Met, Leu-Ala and P(1)' from Pro to Met did not make the protein
      inhibitory to subtilisin, trypsin, chymotrypsin and elastase. The mutations at
      P(1)-P(1)' positions in rcrustinPm1 had no effect on antibacterial activity. The
      WAP domain mutant with both Gly-rich and Cys-rich regions deleted did not exhibit
      antibacterial activity against Staphylococcus aureus while the deletion mutants
      of either Gly-rich or Cys-rich regions exhibited lower antibacterial activity
      than the wild type crustinPm1. Therefore, both Gly-rich and Cys-rich regions
      attached to a WAP domain are essential for efficient antibacterial activity of
      crustinPm1.

PMID- 23010252
TI  - New method of quantifying corneal topographic astigmatism that corresponds with
      manifest refractive cylinder.
AB  - PURPOSE: To derive a method of quantifying corneal topographic astigmatism (CorT)
      that accurately represents manifest refractive cylinder. SETTING: Private
      practice, Melbourne, Australia. DESIGN: Retrospective study. METHOD: Axial power
      measurements obtained using topography in right eyes and left eyes were analyzed.
      For each Placido ring, an astigmatism value was calculated. The ring astigmatism
      values were combined via vector summation to create a new measure termed CorT.
      This parameter was assessed against other commonly used measures of corneal
      astigmatism using the ocular residual astigmatism (ORA) and its standard
      deviation (SD) on how closely each measure matched manifest refractive cylinder.
      The flat meridian of the CorT can also be used to conceptually divide the cornea
      into 2 hemidivisions and a CorT value subsequently calculated for each
      hemidivision of the cornea. RESULTS: The CorT was assessed against other commonly
      used measures of corneal astigmatism using the ORA (0.62 diopters [D] +/- 0.33
      [SD]) and had better correlation with manifest refractive cylinder than manual
      keratometry (K) (ORA 0.68 +/- 0.38 D), simulated K (ORA 0.70 +/- 0.35 D), corneal
      wavefront (ORA 0.74 +/- 0.36 D), and paraxial curvature matching (ORA 0.85 +/-
      0.48 D). The SD of the ORA for CorT was significantly less than the other
      measures of astigmatism (P<.001). CONCLUSIONS: An alternative measure of corneal
      astigmatism, known as CorT, corresponded better to manifest refractive cylinder
      than other commonly used measures. A hemidivisional CorT can also represent the
      nonorthogonal asymmetrical astigmatism in irregular corneas. FINANCIAL
      DISCLOSURE: Dr. Alpins and Mr. Stamatelatos have a financial interest in the
      ASSORT software program used to support the planning and analysis of astigmatic
      correction. Dr. Ong is an employee of ASSORT.

PMID- 23010253
TI  - Perfluoroalkyl substances in polar bear mother-cub pairs: a comparative study
      based on plasma levels from 1998 and 2008.
AB  - Perfluoroalkyl substances (PFASs) are protein-binding blood-accumulating
      contaminants that may have detrimental toxicological effects on the early phases
      of mammalian development. To enable an evaluation of the potential health risks
      of PFAS exposure for polar bears (Ursus maritimus), an exposure assessment was
      made by examining plasma levels of PFASs in polar bear mothers in relation to
      their suckling cubs-of-the-year (~4 months old). Samples were collected at
      Svalbard in 1998 and 2008, and we investigated the between-year differences in
      levels of PFASs. Seven perfluorinated carboxylic acids (?7PFCAs: PFHpA, PFOA,
      PFNA, PFDA, PFUnDA, PFDoDA, and PFTrDA) and two perfluorinated sulfonic acids
      (?2PFSAs: PFHxS and PFOS) were detected in the majority of the mothers and cubs
      from both years. In mothers and cubs, most PFCAs were detected in higher
      concentrations in 2008 than in 1998. On the contrary, levels of PFOS were lower
      in 2008 than in 1998, while levels of PFHxS did not differ between the two
      sampling years. PFOS was the dominating compound in mothers and cubs both in 1998
      and in 2008. Concentration of PFHpA did not differ between mothers and cubs,
      while concentrations of PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFHxS, and PFOS
      were higher in mothers than in their cubs. Except from PFHpA, all compounds
      correlated significantly between mothers and their cubs. The mean cub to mother
      ratios ranged from 0.15 for PFNA to 1.69 for PFHpA. On average (mean+/-standard
      error of mean), the levels of ?7PFCAs and ?2PFSAs in cubs were 0.24+/-0.01 and
      0.22+/-0.01 times the levels in their mothers, respectively. Although maternal
      transfer appears to be a substantial source of exposure for the cubs, the low cub
      to mother ratios indicate that maternal transfer of PFASs in polar bears is
      relatively low in comparison with hydrophobic contaminants (e.g. PCBs). Because
      the level of several PFASs in mothers and cubs from both sampling years exceeded
      the levels associated with health effects in humans, our findings raise concern
      on the potential health effects of PFASs in polar bears from Svalbard. Effort
      should be made to examine the potential health effects of PFASs in polar bears.

PMID- 23010254
TI  - Traffic-related fine and ultrafine particle exposures of professional drivers and
      illness: an opportunity to better link exposure science and epidemiology to
      address an occupational hazard?
AB  - Exposures to traffic-related air pollution (TRAP) can be particularly high in
      transport microenvironments (i.e. in and around vehicles) despite the short
      durations typically spent there. There is a mounting body of evidence that
      suggests that this is especially true for fine (<2.5 um) and ultrafine (<100 nm,
      UF) particles. Professional drivers, who spend extended periods of time in
      transport microenvironments due to their job, may incur exposures markedly higher
      than already elevated non-occupational exposures. Numerous epidemiological
      studies have shown a raised incidence of adverse health outcomes among
      professional drivers, and exposure to TRAP has been suggested as one of the
      possible causal factors. Despite this, data describing the range and determinants
      of occupational exposures to fine and UF particles are largely conspicuous in
      their absence. Such information could strengthen attempts to define the aetiology
      of professional drivers' illnesses as it relates to traffic combustion-derived
      particles. In this article, we suggest that the drivers' occupational fine and UF
      particle exposures are an exemplar case where opportunities exist to better link
      exposure science and epidemiology in addressing questions of causality. The
      nature of the hazard is first introduced, followed by an overview of the health
      effects attributable to exposures typical of transport microenvironments. Basic
      determinants of exposure and reduction strategies are also described, and finally
      the state of knowledge is briefly summarised along with an outline of the main
      unanswered questions in the topic area.

PMID- 23010255
TI  - Exposure to domoic acid through shellfish consumption in Belgium.
AB  - A main known culprit causing amnesic shellfish poisoning in humans is domoic acid
      (DA). The toxin appearance in sea waters (by counting the toxin producing algae)
      and consequently in shellfish is closely monitored to prevent acute intoxications
      with gastrointestinal symptoms and neurological signs. However it is assumed that
      there might be some chronic problems with repetitive exposures to the toxin in
      animals. In humans this is greatly unknown and it is mostly assessed by relating
      reported toxin episodes and representative consumption data. Although in Belgium
      no alarming outbreaks have been reported in recent years, different
      concentrations of DA have been found in shellfish samples. In this study the
      human acute and chronic exposure to DA through shellfish consumption was
      evaluated by linking the data of DA concentrations in samples collected in the
      scope of the National Food control program in the period 2004-2009 and
      consumption data obtained from the National Belgian Food Consumption Survey
      including 3245 adults. The found level of toxin was highest in scallops while
      lowest in mussels. The mean usual long-term intake of molluscs such as scallops,
      mussels and oysters for the whole Belgian population was from 0.10 g/day for
      scallops to 1.21 g/day for mussels. With average portion size estimated to be 56
      108 g/day depending on the shellfish source it was calculated that less than 1%
      of the population would be at risk of acute intoxication. Using a medium bound
      approach, 5-6% of the population shows chronic exposure exceeding the tolerable
      daily intake of 0.075 MUg/kg bw per day with scallops being the most probable
      toxin vector when using lower (68.5%) and medium (45.6%) bound concentrations.

PMID- 23010256
TI  - Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia,
      antipsychotic-naive patients and healthy controls while performing a cognitive
      task.
AB  - BACKGROUND: The dopamine (DA) D2 receptors exist in 2 states: a high-affinity
      state (D2 high) that is linked to second messenger systems, responsible for
      functional effects, exhibits high affinity for agonists (e.g., DA), and a low
      affinity state that is functionally inert exhibits lower affinity for agonists.
      The DA D3 receptor subtype exhibits high agonist affinity, whereas the existence
      of the multiple affinity states is controversial. Preclinical studies in animal
      models of psychosis have shown a selective increase of D2 high as the common
      factor in psychosis, and the D3 receptor has been suggested to be involved in the
      pathophysiology of schizophrenia. METHODS: We studied D2 high and D3 in people at
      clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients
      with schizophrenia using the novel positron emission tomography radiotracer,
      [11C]-(+)-PHNO. The binding potential nondisplaceable (BP(ND)) was examined in
      the regions of interest (ROI; caudate, putamen, ventral striatum, globus
      pallidus, substantia nigra and thalamus) using an ROI and a voxel-wise approach
      while participants performed a cognitive task. RESULTS: We recruited 12 CHR
      individuals and 13 antipsychotic-naive patients with schizophrenia-spectrum
      disorder, whom we compared with 12 age- and sex-matched healthy controls. The
      BP(ND) between patients and controls did not differ in any of the ROIs,
      consistent with the voxel-wise analysis. Correlations between the BP(ND) in D3
      rich regions and psychopathology warrant further investigation. LIMITATIONS: In
      the absence of resting-state (baseline) BP(ND) data, or following a depletion
      paradigm (i.e., alpha-methyl partyrosine), it is not possible to ascertain
      whether the lack of difference among the groups is owing to different levels of
      baseline DA or to release during the cognitive task. CONCLUSION: To our
      knowledge, the present study represents the first effort to measure the D2 and D3
      receptors under a cognitive challenge in individuals putative/prodromal for
      schizophrenia using [11C]-(+)-PHNO.

PMID- 23010258
TI  - From quantitative protein complex analysis to disease mechanism.
AB  - Interest in the field of cilia biology and cilia-associated diseases -
      ciliopathies - has strongly increased over the last few years. Proteomic
      technologies, especially protein complex analysis by affinity purification-based
      methods, have been used to decipher various basic but also disease-associated
      mechanisms. This review focusses on some selected recent studies using affinity
      purification-based protein complex analysis, thereby exemplifying the great
      possibilities this technology offers.

PMID- 23010257
TI  - Recruitment of the left hemispheric emotional attention neural network in risk
      for and protection from depression.
AB  - BACKGROUND: Family history of major depressive disorder (MDD) increases
      individuals' vulnerability to depression and alters the way depression manifests
      itself. Emotion processing and attention shifting are functions altered by MDD
      and family history of the disease; therefore, it is important to recognize the
      neural correlates of these functions in association with both factors. METHODS:
      Our study determines neural correlates of emotion processing and attention
      shifting for healthy individuals and patients with MDD with and without family
      history of depression. We compared the performance and neural activity in a
      functional magnetic resonance imaging experiment examining emotion processing and
      attention shifting in all participants. RESULTS: Our sample included 4 study
      groups: healthy controls without family history of depression (n = 25), patients
      with MDD without family history of the disease (n = 20), unaffected healthy first
      degree relatives of patients with MDD (n = 21) and patients with MDD with family
      history of MDD (n = 30). Compared with healthy controls, unaffected first-degree
      relatives overactivate the somatosensory cortex and the attention controlling
      areas during both emotion processing and attention shifting. Patients with family
      history of MDD have stronger neural activation in subcortical areas during
      shifting attention from negative stimuli. Patients without family history of MDD
      have less activation in the paralimbic regions and more activation in core limbic
      areas, especially during emotion processing. LIMITATIONS: The conclusions about
      the intergroup differences in activation can be drawn only about neural areas
      engaged in the task. CONCLUSION: Unaffected first-degree relatives of patients
      with MDD overreact to external emotional cues and compensate for the
      vulnerability with increased involvement of executive control. Patients with a
      family history of MDD have less executive control over their attentional shifts
      in the face of negative stimuli. Patients without a family history of MDD process
      emotional stimuli in a more visceral way than controls.

PMID- 23010259
TI  - Take the matter into your own hands: a brief review of the effect of nearby-hands
      on visual processing.
AB  - An exciting new line of research that investigates the impact of one's own hands
      on visual perception and attention has flourished in the past several years.
      Specifically, several studies have demonstrated that the nearness of one's hands
      can modulate visual perception, visual attention, and even visual memory. These
      studies together shed new light on how the brain prioritizes certain information
      to be processed first. This review first outlines the recent progress that has
      been made to uncover various characteristics of the nearby-hand effect, including
      how they may be transferred to a familiar tool. We then summarize the findings
      into four specific characteristics of the nearby-hand effect, and conclude with a
      possible neural mechanism that may account for all the findings.

PMID- 23010260
TI  - Hemophilic arthropathy in patients with von Willebrand disease.
AB  - von Willebrand disease (VWD) affects approximately 1% of the population. Joint
      bleeds are not a predominant symptom of VWD, however they do occur. Especially in
      patients with severe VWD, joint bleeds have been described in up to 45% of the
      patients. Recurrent hemarthroses can lead to joint destruction which is the main
      cause of morbidity, as is observed in hemophilia patients. In VWD however, the
      occurrence, severity, onset, treatment and impact of arthropathy have not been
      well described. This literature review summarizes all publications on arthropathy
      in patients with hereditary VWD, published until 1-5-2012. Joint bleeds in VWD
      are associated with low FVIII levels and seem to occur at young age. Depending on
      the severity of VWD, arthropathy occurs in 2-30% of the patients. Radiological
      joint damage can be seen but has not systematically been studied. Arthropathy can
      affect daily functioning and interfere with the quality of life. For acute
      management of joint bleeds FVIII/VWF concentrates can be used in VWD patients
      unresponsive to desmopressin or desmopressin in responsive VWD patients. When
      severe joint bleeds have caused synovitis and arthropathy, chemical or
      radioactive synovectomy and surgical joint procedures seem feasible to prevent
      further joint damage. Additional research is needed to learn more about the
      severity, onset and impact of arthropathy in VWD. Ongoing studies will hopefully
      answer the question whether prophylactic treatment with coagulation factor
      concentrates should be considered standard of care in severe VWD to prevent
      arthropathy.

PMID- 23010262
TI  - Discovery of phosphoinositide 3-kinases (PI3K) p110beta isoform inhibitor 4-[2
      hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin
      2-one, an effective antithrombotic agent without associated bleeding and insulin
      resistance.
AB  - Structure-based evolution of the original fragment leads resulted in the
      identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2
      methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective
      phosphoinositide 3-kinases (PI3K) p110beta isoform inhibitor with favourable in
      vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not
      significantly increase bleeding time in dogs. Additionally, due to its enhanced
      selectivity over p110alpha, (S)-21 did not induce any insulin resistance in rats.

PMID- 23010261
TI  - The clinical characteristics and outcome of intracardiac thrombus and aortic
      valvular involvement in Behcet's disease: an analysis of 20 cases.
AB  - OBJECTIVES: To assess the clinical characteristics and outcome of patients with
      cardiac Behcet's disease(BD). METHODS: Medical charts of 20 cardiac BD patients
      admitted in Peking Union Medical College Hospital from June 1996 to June 2011
      were systematically reviewed, including demographic data, clinical features,
      laboratory and histopathology findings and outcome. RESULTS: Patients age ranged
      19~57 yrs[mean (35+/-10) yrs], included 17 males and 3 females. Six (30%) of them
      did not fulfill the ISG criteria at cardiac onset, and fourteen (70%) of them
      experienced heart failure. Echocardiography findings included intracardiac
      thrombus (n=7), and aortic valve involvement with left ventricular enlargement
      and severe aortic regurgitation (n=13). Eight patients underwent surgery before
      efficient immunosuppressant treatment, and five (62.5%) underwent re-operation
      due to recurrence of thrombus or valvular dehiscence and severe paravalvular
      leakage. Histopathology findings revealed predominantly inflammatory cells
      infiltration, thrombus and fibrous tissue formation. After initiation of
      prednisone plus immunosuppressant, patients were followed up for 6~42 months
      (mean 14.8+/-9.9 months), the intracardiac thrombus disappeared or decreased in
      size in five cases, remained stable after surgery in the other two cases, and the
      heart failure disappeared in all patients with aortic involvement. CONCLUSIONS:
      Cardiac BD affects males more than females, and is prone to delayed diagnosis
      because some patients do not have typical clinical manifestations at cardiac
      onset; Corticosteroids plus immunosuppressants reduce the thrombus and improve
      aortic regurgitation and heart failure in cardiac BD, whereas surgery alone does
      not lead to complete resolution.

PMID- 23010263
TI  - Synthesis and in vitro antitumour screening of 2-(beta-D-xylofuranosyl)thiazole-4
      carboxamide and two novel tiazofurin analogues with substituted
      tetrahydrofurodioxol moiety as a sugar mimic.
AB  - 2-(beta-D-xylofuranosyl)thiazole-4-carboxamide (2) and two new tiazofurin
      analogues with 5-hydroxymethyl-2-methyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-ol
      moiety as a sugar mimic (27 and 28) have been synthesized and evaluated for their
      in vitro antitumour activity against a panel of human tumour cell lines (K562, HL
      60, Jurkat, Raji and HeLa). In contrast to previous literature reports, a
      metabolic MTT assay revealed remarkable cytotoxicity of 2 against K562
      (IC(50)=0.15 MUM) and HL-60 (IC(50)=0.13 MUM) cells. Flow cytometry data suggest
      that cytotoxic effects of analogue 2 in the culture of K562 cells might be
      mediated by apoptosis, in opposite to tiazofurin, which did not induce apoptosis
      of K562 cells after 24h, thus suggesting a different mechanism of action. All
      three analogues 2, 27 and 28 were also active against Jurkat, Raji and HeLa
      cells, with IC(50) values in the range from 0.06 to 5.61 MUM, but were completely
      inactive against the normal foetal lung fibroblasts (MRC-5).

PMID- 23010264
TI  - [18F](R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-(2-fluoroethoxy)-2,5
      dimethyl phenylamino)pyrazin-2(1H)-one: introduction of N3-phenylpyrazinones as
      potential CRF-R1 PET imaging agents.
AB  - Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic
      stability, compound 10 was evaluated for potential development as PET
      radioligand. Compound [(18)F]10 was prepared with high radiochemical purity and
      showed promising binding properties in rat brain imaging experiments.

PMID- 23010265
TI  - Synthesis and evaluation of naphthoic acid derivatives as fluorescent probes to
      screen advanced glycation end-products breakers.
AB  - Advanced glycation end-products, namely AGEs, are involved in the pathogenesis of
      numerous diseases. If AGEs inhibitors are well-known, only few products are
      described as compounds able to destroy those deleterious products. In this work,
      we describe naphthoic acid derivatives, particularly 1-(naphthalen-1-yl)propane
      1,2-dione 9, allowing the simple and rapid detection of AGEs breakers using a 96
      well microplate fluorescence assay. Since the inaugurate publication about AGEs
      breakers whose activity was demonstrated using HPLC analysis, this work proposes
      the first assay suitable for automated and high throughput screening of AGEs
      breakers.

PMID- 23010266
TI  - Novel histone deacetylase 8 ligands without a zinc chelating group: exploring an
      'upside-down' binding pose.
AB  - A novel series of HDAC8 inhibitors without a zinc-chelating hydroxamic acid
      moiety is reported. Photoaffinity labeling and molecular modeling studies suggest
      that these ligands are likely to bind in an 'upside-down' fashion in a secondary
      binding site proximal to the main catalytic site. The most potent ligand in the
      series exhibits an IC(50) of 28 MUM for HDAC8 and is found to inhibit the
      deacetylation of H4 but not alpha-tubulin in SH-SY5Y cell line.

PMID- 23010267
TI  - Novel sulfanylphthalimide analogues as highly potent inhibitors of monoamine
      oxidase B.
AB  - Monoamine oxidase (MAO) plays an essential role in the catabolism of
      neurotransmitter amines. The two isoforms of this enzyme, MAO-A and -B, are
      considered to be drug targets for the therapy of depression and neurodegenerative
      diseases, respectively. Based on a recent report that the phthalimide moiety may
      be a useful scaffold for the design of potent MAO-B inhibitors, the present study
      examines a series of 5-sulfanylphthalimide analogues as potential inhibitors of
      both human MAO isoforms. The results document that 5-sulfanylphthalimides are
      highly potent and selective MAO-B inhibitors with all of the examined compounds
      possessing IC(50) values in the nanomolar range. The most potent inhibitor, 5
      (benzylsulfanyl)phthalimide, exhibits an IC(50) value of 0.0045 MUM for the
      inhibition of MAO-B with a 427-fold selectivity for MAO-B compared to MAO-A. We
      conclude that 5-sulfanylphthalimides represent an interesting class of MAO-B
      inhibitors and may serve as lead compounds for the design of antiparkinsonian
      therapy.

PMID- 23010268
TI  - Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying
      prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole
      templates.
AB  - A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core
      structure with different prime side alkyl substituted 4,5,6,7
      tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized.
      Striking differences were observed on potencies in the BACE-1 enzymatic and
      cellular assays depending on the nature of the heteroatoms in the bicyclic ring,
      from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of
      44 nM (enzyme assay) and 65 nM (cell-based assay).

PMID- 23010270
TI  - Synthesis and pharmacological evaluation of N-substituted 2-(2-oxo-2H-chromen-4
      yloxy)propanamide as cyclooxygenase inhibitors.
AB  - A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide
      derivatives were synthesized via converting the readily available 4-hydroxy
      coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate
      followed by hydrolysis and then reacting with different substituted amines. The
      molecular structures of two representative compounds, that is, 3 and 5l were
      confirmed by single crystal X-ray diffraction study. All the compounds
      synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties
      in vitro. The compound 5i showed balanced selectivity towards COX-2 over COX-1
      inhibition and good docking scores when docked into the COX-2 protein.

PMID- 23010269
TI  - Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate
      (ML221) as a functional antagonist of the apelin (APJ) receptor.
AB  - The recently discovered apelin/APJ system has emerged as a critical mediator of
      cardiovascular homeostasis and is associated with the pathogenesis of
      cardiovascular disease. A role for apelin/APJ in energy metabolism and
      gastrointestinal function has also recently emerged. We disclose the discovery
      and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4
      nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays
      that is >37-fold selective over the closely related angiotensin II type 1 (AT1)
      receptor. ML221 was derived from an HTS of the ~330,600 compound MLSMR
      collection. This antagonist showed no significant binding activity against 29
      other GPCRs, except to the kappa-opioid and benzodiazepinone receptors (<50/<70%I
      at 10 MUM). The synthetic methodology, development of structure-activity
      relationship (SAR), and initial in vitro pharmacologic characterization are also
      presented.

PMID- 23010271
TI  - Novel cyanocombretastatins as potent tubulin polymerisation inhibitors.
AB  - A series of novel cyanocombretastatins bearing a 3,4,5-trimethoxyphenyl moiety
      combined with a variety of substituted phenyl rings, were synthesised and their
      antitumour activity was evaluated. The Z-cyanocombretastatins were synthesised in
      a one-step protocol in high purity and yield. Fluoro, bromo, iodo, and
      derivatives with boronic acid and an ethyne function at meta position of the B
      ring were synthesised. In vitro MTT bioassays against human chronic myelogenous
      leukaemia (K562) and transfected breast adenocarcinoma (MDA NQO1) cell lines,
      revealed promising IC(50) inhibitory values in nanomolar range (<50 nM).
      Introduction of a nitrile function on the olefinic bond not only increased the
      cytotoxicity of the less active Z-isomers but rendered the analogues as moderate
      to potent inhibitors of tubulin polymerisation comparable to that of CA-4
      (IC(50)=2.2 MUM).

PMID- 23010272
TI  - Design, synthesis and in vitro activities on anti-platelet aggregation of 4
      methoxybenzene-1,3-isophthalamides.
AB  - On the purpose of searching for the structure-activity relationship (SAR) and
      obtaining novel anti-platelet drugs, 41 4-methoxybenzene-1,3-isophthalamides have
      been described the synthesis process and in vitro activities on anti-platelet
      aggregation. The target compounds have been classified into four series: series 1
      (ortho-substituted phenyl: 1a-1j), series 2 (meta-substituted phenyl: 2a-2k),
      series 3 (para-substituted phenyl: 3a-3l) and series 4 (aromatic of no
      substituted group and aromatic heterocyclic substituted groups: 4a-4h). The
      chemical structures of the target compounds were confirmed by MS, IR, (1)H NMR,
      and their in vitro activities on anti-platelet aggregation were tested and
      assessed by using Born test. The result showed that thirteen compounds 1c, 1d,
      1i, 1j, 2g, 3a, 3c, 3d, 3f, 3h, 3l, 4b and 4c have superior anti-platelet
      aggregation activities than the reference drug Picotamide.

PMID- 23010274
TI  - Discovery of 4-morpholino-pyrimidin-6-one and 4-morpholino-pyrimidin-2-one
      containing Phosphoinositide 3-kinase (PI3K) p110beta isoform inhibitors through
      structure-based fragment optimisation.
AB  - The discovery of 4-morpholino-pyrimidin-6-one and 4-morpholino-pyrimidin-2-one
      containing inhibitors of Phosphoinositide 3-kinases (PI3K) p110beta isoform is
      reported. Structure-based optimisation of the original fragment hit resulted in
      lead compounds with improvements in ligand efficiency, lipophilicity efficiency,
      p110beta potency and selectivity over p110alpha.

PMID- 23010273
TI  - Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV
      1 by the combination of resveratrol and decitabine.
AB  - Ribonucleotide reductase inhibitors enhance the anti-HIV-1 activities of a
      variety of nucleoside analogs, including those that act as chain terminators and
      those that increase the HIV-1 mutation rate. However the use of these
      ribonucleotide reductase inhibitors is limited by their associated toxicities.
      The hydroxylated phytostilbene resveratrol has activity in a host of systems
      including inhibition of ribonucleotide reductase and has minimal toxicity. Here
      we synthesized derivatives of resveratrol and examined them for anti-HIV-1
      activity and their ability to enhance the antiviral activity of decitabine, a
      nucleoside analog that decreases viral replication by increasing the HIV-1
      mutation rate. The data demonstrates that six of the derivatives have anti-HIV-1
      activity greater than resveratrol. However, only resveratrol acted in synergy
      with decitabine to inhibit HIV-1 infectivity. These results reveal novel
      resveratrol derivatives with anti-HIV-1 activity that may have mechanisms of
      action that differ from the drugs currently used to treat HIV-1.

PMID- 23010275
TI  - Antipsychotic drug use-understanding the recent attention and response to the
      increased scrutiny.

PMID- 23010276
TI  - Nutrition in hospitals: mealtimes matter.

PMID- 23010277
TI  - Commentary on "Changes in the aetiological spectrum of leg ulcers after a broad
      scale intervention in a defined geographical population in Sweden".

PMID- 23010278
TI  - Stimulation of the Na(+)-coupled glucose transporter SGLT1 by B-RAF.
AB  - Gain of function mutations of B-RAF, a serine/threonine protein kinase may lead
      to development of tumor cells. As tumor cells mainly utilize glucose as fuel,
      their survival critically depends on their ability to accumulate glucose from
      extracellular space. The Na(+)-coupled glucose transporter SGLT1 accomplishes
      concentrative cellular glucose uptake against a chemical glucose gradient and
      thus even at low extracellular glucose concentrations. SGLT1 contributes to
      glucose uptake in several tumor cells. The present study thus explored whether B
      RAF activates SGLT1. To this end, SGLT1 was expressed in Xenopus oocytes with or
      without additional coexpression of B-RAF and electrogenic glucose transport was
      determined by dual electrode voltage clamp. In SGLT1-expressing oocytes but not
      in oocytes injected with water the addition of glucose to the extracellular bath
      generated a current (I(g)), which was significantly increased following
      coexpression of wild-type B-RAF. According to kinetic analysis, coexpression of B
      RAF enhanced the maximal transport rate without significantly modifying the
      affinity of the carrier. According to chemiluminescence and confocal microscopy
      experiments, B-RAF enhanced the Na(+)-coupled glucose transporter SGLT1 protein
      abundance in the cell membrane. Exposure of the Xenopus oocytes to Brefeldin A
      (5MUM), an inhibitor of vesicle insertion, was followed by a decline of I(g),
      which was higher in oocytes expressing SGLT1 together with B-RAF than in oocytes
      expressing SGLT1 alone. In conclusion, B-RAF upregulates SGLT1 activity, an
      effect requiring vesicle insertion into the cell membrane.

PMID- 23010279
TI  - Analysis of HLA-DRB3 alleles and supertypical genotypes in the MHC Class II
      region in sporadic inclusion body myositis.
AB  - We compared the carriage frequencies of HLA-DRB3 and its major alleles and of HLA
      DRB4 and HLA-DRB5 in an Australian sIBM cohort and a population control group who
      had previously been genotyped for the HLA-DRB1*03:01 risk allele. There was a
      strong disease association with the carriage of the DRB3*01:01 allele which was
      accounted for by its linkage disequilibrium with DRB1*03:01. The carriage of HLA
      DRB4 was found to be strongly protective and abrogated the risk effect of HLA
      DRB1*03:01. The findings indicate that haplotypic combinations of alleles at the
      HLA-DRB1 and secondary HLA-DRB loci have important risk modifying effects in
      sIBM.

PMID- 23010280
TI  - Low dose zymosan ameliorates both chronic and relapsing experimental autoimmune
      encephalomyelitis.
AB  - Zymosan has previously been reported to have both pro-inflammatory and anti
      inflammatory effects. Here we demonstrate that low dose zymosan prevented or
      reversed chronic and relapsing paralysis in EAE. In suppressing CNS autoimmune
      inflammation, zymosan not only regulated APC costimulator and MHC class II
      expression, but also promoted differentiation of regulatory T cells. Following
      adoptive transfer of zymosan-primed CD4(+) T cells, recipient mice were protected
      from EAE. In contrast, a MAPK inhibitor and a blocker of beta-glucan, reversed
      the effects of zymosan. These results demonstrate that zymosan may be a promising
      beneficial agent for Multiple Sclerosis (MS).

PMID- 23010281
TI  - beta-Lapachone ameliorization of experimental autoimmune encephalomyelitis.
AB  - beta-Lapachone is a naturally occurring quinine, originally isolated from the
      bark of the lapacho tree (Tabebuia avellanedae) which is currently being
      evaluated in clinical trials for the treatment of cancer. In addition, recent
      investigations suggest its potential application for treatment of inflammatory
      diseases. Multiple sclerosis (MS) is an autoimmune disorder characterized by CNS
      inflammation and demyelination. Reactive T cells including IL-17 and IFN-gamma
      secreting T cells are believed to initiate MS and the associated animal model
      system experimental autoimmune encephalomyelitis (EAE). IL-12 family cytokines
      secreted by peripheral dendritic cells (DCs) and CNS microglia are capable of
      modulating T-cell phenotypes. The present studies demonstrated that beta
      lapachone selectively inhibited the expression of IL-12 family cytokines
      including IL-12 and IL-23 by DCs and microglia, and reduced IL-17 production by
      CD4(+) T-cells indirectly through suppressing IL-23 expression by microglia.
      Importantly, our studies also demonstrated that beta-lapachone ameliorated the
      development on EAE. beta-Lapachone suppression of EAE was associated with
      decreased expression of mRNAs encoding IL-12 family cytokines, IL-23R and IL
      17RA, and molecules important in Toll-like receptor signaling. Collectively,
      these studies suggest mechanisms by which beta-lapachone suppresses EAE and
      suggest that beta-lapachone may be effective in the treatment of inflammatory
      diseases such as MS.

PMID- 23010282
TI  - Atmospheric transport of speciated mercury across southern Lake Michigan:
      Influence from emission sources in the Chicago/Gary urban area.
AB  - Quantifying the local and regional impacts of speciated mercury (Hg) emissions
      from major urban and industrial areas is critical for understanding Hg transport
      and cycling in the environment. The Chicago/Gary urban area is one location where
      Hg emissions from industrial sources are significant and the regional transport
      of emissions may contribute to elevated ambient Hg concentrations at downwind
      locations. From July to November 2007, we collected semi-continuous measurements
      of gaseous elemental Hg (Hg(0)), fine particulate bound Hg (Hgp), and divalent
      reactive gaseous Hg (RGM) in Chicago, IL and Holland, MI to characterize the
      impact of Chicago/Gary source emissions on Hg concentrations in southwest
      Michigan and to improve our overall understanding of speciated Hg transport and
      deposition. The mean (and median) concentrations of Hg(0), Hgp, and RGM in
      Chicago were 2.5ng/m(3) (1.9ng/m(3)), 9pg/m(3) (5pg/m(3)), and 17pg/m(3)
      (6pg/m(3)), respectively. In Holland the mean (and median) concentrations were
      1.3ng/m(3) (1.3ng/m(3)), 6pg/m(3) (6pg/m(3)), and 8pg/m(3) (2pg/m(3)),
      respectively. Cluster analysis of 24-hour HYSPLIT back-trajectories associated
      with the semi-continuous Hg measurements indicated that southwest transport from
      Chicago/Gary to Holland occurred during approximately 27% of the study. In
      Holland, under this transport regime, we observed a five-fold increase in RGM
      relative to the median concentration of the other transport clusters. We applied
      the HYSPLIT dispersion model to two case study periods to further quantify the
      impact of Chicago/Gary sources on southeast Michigan and investigate the role of
      direct transport and dispersion of speciated Hg emissions. Results suggested that
      more than 50% of the maximum RGM concentrations observed in Holland during the
      selected periods could be attributed to direct transport of primary RGM emissions
      from Chicago/Gary. The remaining RGM fractions are believed to be associated with
      Hg(0) oxidation during transport over Lake Michigan.

PMID- 23010283
TI  - Stability study and lyophilization of vitamin E-loaded nanocapsules prepared by
      membrane contactor.
AB  - In this research, we studied the accelerated stability of vitamin E-loaded
      nanocapsules (NCs) prepared by the nanoprecipitation method. Vitamin E-loaded NCs
      were optimized firstly at the laboratory scale and then scaled up using the
      membrane contactor technique. The optimum conditions of the membrane contactor
      preparation (pilot scale) produced vitamin E-loaded NCs with an average size of
      253 nm, polydispersity index 0.19 and a zeta potential -16 mV. The average size,
      polydispersity index and zeta potential values were 185 nm, 0.12 and -15 mV,
      respectively for the NCs prepared at laboratory scale. No significant changes
      were noticed in these values after 3 and 6 months of storage at high temperature
      (40+/-2  degrees C) and relative humidity (75+/-5%) in spite of vitamin E
      sensitivity to light, heat and oxygen. The entrapment efficiency of NCs prepared
      at pilot scale was 97% at the beginning of the stability study, and became (95%,
      59%) after 3 and 6 months of storage, respectively. These values at lab-scale
      were (98%, 96%, and 89%) at time zero and after 3 and 6 months of storage,
      respectively. This confirms the ability of vitamin E encapsulation to preserve
      its stability, which is one major goal of our work. Lyophilization of the
      optimized formula at lab-scale was also performed. Four types of cryoprotectants
      were tested (poly(vinyl pyrrolidone), sucrose, mannitol, and glucose). Freeze
      dried NCs prepared with sucrose were found acceptable. The other lyophilized NCs
      obtained at different conditions presented large aggregates.

PMID- 23010285
TI  - Beyond the antibiotic prophylaxis of infective endocarditis: the problem of
      dental surveillance.

PMID- 23010284
TI  - Modification of concomitant drug release from oil vehicles using drug-prodrug
      combinations to achieve sustained balanced analgesia after joint installation.
AB  - Intra-articular injection of two drugs in a sustained drug delivery system
      combining the use of lipophilic solution with the prodrug approach may provide
      efficient and prolonged postoperative pain treatment after arthroscopic
      procedures. In the present study, the concomitant release of N,N-diethyl
      glycolamide ester of naproxen and ropivacaine from an oil vehicle consisting of
      medium-chain triglycerides were investigated in vitro. The release into both
      phosphate buffer and 80% (v/v) synovial fluid at pH 7.4 was examined in two
      dialysis membrane-based release models. The ester prodrug exhibited high
      solubility in medium-chain triglyceride, a high partition coefficient and was
      rapidly converted to naproxen in synovial fluid. Compared to naproxen, the
      release of the prodrug from the oil was sustained. In synovial fluid, the
      reconversion to naproxen resulted in faster release compared to that observed
      using buffer. In both release models, the use of ropivacaine-prodrug combination
      provided concomitant release from the oil into synovial fluid with ropivacaine
      being released faster than naproxen. The use of lipophilic prodrugs that are
      converted fast to the parent drug in synovial fluid seems to be a feasible
      approach to obtain prolonged joint residence time.

PMID- 23010286
TI  - Trends and predictors of rehospitalisation following an acute coronary syndrome:
      report from the Australian and New Zealand population of the Global Registry of
      Acute Coronary Events (GRACE).
AB  - BACKGROUND: Readmission following an acute coronary syndrome (ACS) is frequent in
      our community. Patient specific factors identifying those at risk of readmission
      are poorly described. METHODS: Data were analysed from 5219 patients with an ACS
      enrolled in the Australian and New Zealand population of the Global Registry of
      Acute Coronary Events (GRACE) between 1999 and 2007. Patients who were readmitted
      for cardiovascular disease within 6 months of discharge were identified;
      regression analysis was used to predict independent patient factors associated
      with readmission 1 month and 1-6 months after discharge. RESULTS: 1048 patients
      (20.1%) were readmitted within 6 months, with a significant proportion (n=434,
      41.4%) of readmissions occurring within 30 days of discharge. Readmission within
      6 months was associated with a higher incidence of unscheduled cardiac
      catheterisation (HR 25.64, 95% CI 18.41 to 35.71), unscheduled percutaneous
      coronary intervention (PCI) (HR 15.78, 95% CI 10.56 to 23.59), stroke (HR 1.92,
      95% CI 1.08 to 3.43), and death (HR 2.40, 95% CI 1.66 to 3.49). Recurrent
      ischemia in hospital and a diagnosis of S-T elevation myocardial infarction
      during the index admission were associated with the strongest risk of early
      rehospitalisation, while revascularisation by PCI or coronary artery bypass
      surgery (CABG) was associated with lowest risk of early readmission. A history of
      heart failure, prior myocardial infarction or angina was associated with a
      greater likelihood of later rehospitalisation, whereas revascularisation by CABG
      was associated with the lowest risk of later rehospitalisation. CONCLUSIONS:
      Several patient and clinical factors identify patients at higher risk of
      readmission. Identifying these factors and escalating in-hospital and post
      discharge care for these higher risk patients may prevent readmission and improve
      outcome.

PMID- 23010287
TI  - Comprehensive assessment of a quadricuspid aortic valve and coronary arteries by
      multidetector cardiac CT.

PMID- 23010288
TI  - High-density lipoproteins and cardiovascular disease: the plots thicken.

PMID- 23010289
TI  - Subclinical atrial fibrillation: how hard should we look?

PMID- 23010290
TI  - Do early experiences with cannabis vary in cigarette smokers?
AB  - INTRODUCTION: We examine whether regular cigarette smokers were more likely to be
      exposed to and use cannabis at an earlier age, and further, upon initiation,
      whether their initial experiences with cannabis varied from those reported by
      never/non-regular cigarette smokers. METHOD: A sample of 3797 Australian twins
      and siblings aged 21-46 years was used. Survival analyses examined whether
      cigarette smokers were at increased likelihood of early opportunity to use
      cannabis and early onset of cannabis use. Logistic regression examined whether
      cigarette smokers reported greater enjoyment of their cannabis experience,
      inhaling on the first try, differing positive and negative initial subjective
      reactions, smoked cigarettes with cannabis the first time and were more likely to
      try cannabis again within a week. RESULTS: Regular cigarette smokers were more
      likely to report an earlier opportunity to use cannabis and early onset of
      cannabis use. Regular cigarette smokers were also considerably more likely to
      have enjoyed their first experience with cannabis and reported higher rates of
      positive initial reactions. They were more likely to report inhaling on the first
      try and smoking cigarettes with cannabis. Potentially negative subjective
      reactions were also elevated in regular cigarette smokers. Importantly, cigarette
      smokers were at 1.87 increased odds of smoking cannabis within a week of their
      initial use. CONCLUSION: These findings indicate that the well-known overlap in
      cannabis and cigarette smoking behaviors may evolve as early as opportunity to
      use and extend through the course of the substance use trajectory.

PMID- 23010291
TI  - Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based
      nationwide cohort study.
AB  - The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are
      very sensitive to drugs that interfere with the folic acid cycle and thereby
      inhibit DNA synthesis, use of trimethoprim during the first trimester could be
      associated with miscarriage. A nationwide cohort study including all women in
      Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used
      nationwide registers to identify all women giving birth, having a record of
      miscarriage or induced abortion. Data on exposure to trimethoprim were obtained
      from the National Prescription Register. Cox proportional hazard regression
      analysis with exposure to trimethoprim as a time-dependent variable was used to
      estimate the risk of miscarriage. The adjusted hazard ratio of having a
      miscarriage after exposure to trimethoprim in the first trimester compared to non
      exposure was 2?04 (95% confidence interval 1?43-2?91). Our results indicate that
      trimethoprim exposure in the first trimester is associated with a doubling of the
      hazard of miscarriage.

PMID- 23010292
TI  - Trypanosoma cruzi uses macropinocytosis as an additional entry pathway into
      mammalian host cell.
AB  - Several intracellular pathogens are internalized by host cells via multiple
      endocytic pathways. It is no different with Trypanosoma cruzi. Evidences indicate
      that T. cruzi entry may occur by endocytosis/phagocytosis or by an active manner.
      Although macropinocytosis is largely considered an endocytic process where cells
      internalize only large amounts of solutes, several pathogens use this pathway to
      enter into host cells. To investigate whether T. cruzi entry into peritoneal
      macrophages and LLC-MK2 epithelial cells can be also mediated through a
      macropinocytosis-like process, we used several experimental strategies presently
      available to characterize macropinocytosis such as the use of different
      inhibitors. These macropinocytosis' inhibitors blocked internalization of T.
      cruzi by host cells. To further support this, immunofluorescence microscopy and
      scanning electron microscopy techniques were used. Field emission scanning
      electron microscopy revealed that after treatment, parasites remained attached to
      the external side of host cell plasma membrane. Proteins such as Rabankyrin 5,
      tyrosine kinases, Pak1 and actin microfilaments, which participate in
      macropinosome formation, were localized at T. cruzi entry sites. We also observed
      co-localization between the parasite and an endocytic fluid phase marker. All
      together, these results indicate that T. cruzi is able to use multiple mechanisms
      of penetration into host cell, including macropinocytosis.

PMID- 23010293
TI  - Functional characteristics of the novel, human-derived recombinant FVIII protein
      product, human-cl rhFVIII.
AB  - INTRODUCTION: Hemophilia A is routinely treated by administration of exogenous
      coagulation factor VIII (FVIII). As safety and efficacy of FVIII products have
      improved over the years, development of FVIII-neutralizing antibodies (FVIII
      inhibitors) has emerged as the most serious complication. The new human cell line
      derived recombinant human FVIII (human-cl rhFVIII) is the first recombinant FVIII
      product produced in a human cell line without additive animal proteins, with a
      goal of minimizing the risk of inhibitor development. MATERIALS AND METHODS:
      Biochemical analyzes of purity, molecular and functional attributes of the novel
      human-cl rhFVIII were undertaken for product characterization. RESULTS AND
      CONCLUSIONS: Human-cl rhFVIII was shown to be highly pure, with host-cell protein
      and DNA traces comparable to, or lower than, currently marketed recombinant FVIII
      (rFVIII) products. Human-cl rhFVIII was shown to have high specific FVIII
      activity and characteristics similar to full-length rFVIII products. Furthermore,
      no significant discrepancy between one-stage and chromogenic assay results were
      observed for human-cl rhFVIII, indicating potency ratios of these assays
      comparable to the full-length rFVIII products. In functional tests, human-cl
      rhFVIII exhibited physiological thrombin generation and a normal rate of
      inactivation by activated protein C. Importantly, human-cl rhFVIII displayed
      higher binding capacity with von Willebrand factor than comparator products, thus
      minimizing circulating unbound FVIII and further reducing the potential risk of
      inhibitor development.

PMID- 23010294
TI  - Atorvastatin-associated necrotising inflammatory myopathy.

PMID- 23010295
TI  - Prognostic value of telomere length in acute coronary syndrome.
AB  - Telomere and telomerase are involved in cellular and organismal ageing and have
      been related to human diseases. Coronary artery disease is one of the most common
      age-related health problems in developed countries. Nevertheless, the specific
      role of cellular ageing in this process is still unclear. In this study, we
      analyze the possible prognostic value of telomere length and telomerase
      polymorphisms in a population of 150 middle aged males (mean age 62 +/- 7)
      admitted for acute coronary syndrome who were followed up for more than 600 days.
      Peripheral blood samples were obtained and relative and comparative qPCR was used
      to measure telomere length and real time PCR to study the polymorphisms. Two
      prognostic combined events were defined. Long telomere length was revealed as an
      independent predictor (protector) of combined event presentation during long term
      follow up in our patients.

PMID- 23010296
TI  - A rare cause of rectal bleeding.

PMID- 23010297
TI  - Genotypes and phenotypes: animal models of familial adenomatous polyposis coli.

PMID- 23010298
TI  - An uncommon cause of ulceroinfiltrative gastric wall thickening in a young
      patient.

PMID- 23010299
TI  - Incidental endoscopic finding of foreign material in the duodenum.

PMID- 23010300
TI  - Acute gastric outlet obstruction after left hemicolectomy.

PMID- 23010301
TI  - An unusual cause of abdominal pain.

PMID- 23010302
TI  - Abdominal cystic mass in an adolescent.

PMID- 23010303
TI  - Hepatocellular carcinoma surveillance: all cirrhotic patients may not be equal.

PMID- 23010304
TI  - Abdominal distension in an infant.

PMID- 23010306
TI  - 160th ENMC International Workshop (First ENMC practical care workshop) Exercise
      training in patients with muscle diseases: 20-22 June 2008, Naarden, The
      Netherlands.

PMID- 23010307
TI  - Targeted array comparative genomic hybridization--a new diagnostic tool for the
      detection of large copy number variations in nemaline myopathy-causing genes.
AB  - Nemaline myopathy (NM) constitutes a heterogeneous group of congenital
      myopathies. Mutations in the nebulin gene (NEB) are the main cause of recessively
      inherited NM. NEB is one of the most largest genes in human. To date, 68 NEB
      mutations, mainly small deletions or point mutations have been published. The
      only large mutation characterized is the 2.5 kb deletion of exon 55 in the
      Ashkenazi Jewish population. To investigate any copy number variations in this
      enormous gene, we designed a novel custom comparative genomic hybridization
      microarray, NM-CGH, targeted towards the seven known genes causative for NM.
      During the validation of the NM-CGH array we identified two novel deletions in
      two different families. The first is the largest deletion characterized in NEB to
      date, (~53 kb) encompassing 24 exons. The second deletion (1 kb) covers two
      exons. In both families, the copy number change was the second mutation to be
      characterized and shown to have been inherited from one of the healthy carrier
      parents. In addition to these novel mutations, copy number variation was
      identified in four samples in three families in the triplicate region of NEB. We
      conclude that this method appears promising for the detection of copy number
      variations in NEB.

PMID- 23010308
TI  - Bifidobacterium spp. influences the production of autoinducer-2 and biofilm
      formation by Escherichia coli O157:H7.
AB  - The effect of Bifidobacterium spp. on the production of quorum-sensing (QS)
      signals and biofilm formation by enterohemorrhagic Escherichia coli (EHEC)
      O157:H7 was investigated. In an AI-2 bioassay, cell extracts of Bifidobacterium
      longum ATCC 15707 resulted in a 98-fold reduction in AI-2 activity in EHEC
      O157:H7 as well as in the Vibrio harveyi reporter strain, even though they did
      not inhibit the growth of EHEC O157:H7. In addition, they resulted in a 36%
      reduction in biofilm formation by the organism. Consistently, the virulence of
      EHEC O157:H7 was significantly attenuated by the presence of cell extracts of B.
      longum ATCC 15707 in the Caenorhabditis elegans nematode in vivo model. By a
      proteome analysis using two dimensional electrophoresis (2-DE), we determined
      that seven proteins including formation of iron-sulfur protein (NifU),
      thiol:disulfide interchange protein (DsbA), and flagellar P-ring protein (FlgI)
      were differentially regulated in the EHEC O157:H7 when supplemented with cell
      extracts of B. longum ATCC 15707. Taken together, these findings propose a novel
      function of a dairy adjunct in repressing the virulence of EHEC O157:H7.

PMID- 23010309
TI  - [Hospitalized nonagenarians: a new challenge in the geriatric care].

PMID- 23010310
TI  - Dopaminergic axons preferentially innervate dendritic spines with hyperactive
      glutamatergic synapses in the rat striatum.
AB  - Dopaminergic and glutamatergic afferents simultaneously innervate median spiny
      neurons (MSNs) and interact to mediate basal ganglia functions. However, the
      association between dopaminergic and glutamatergic axons is not clear. In the
      present study, nigrostriatal, corticostriatal, and thalamostriatal axons were
      anterogradely traced with biotinylated dextran amines (BDA) in rats, and MSNs
      were labeled with chloromethylbenzamido-DiI for neurogeometric analysis. Results
      showed that nigrostriatal, but not corticostriatal or thalamostriatal, axons were
      biased to a target on dendritic spines of the MSNs. In addition, the MSN
      dendritic spines, which were innervated by tyrosine hydroxylase-immunoreactive
      (TH-IR) axons and vesicular glutamate transporter 1 or 2-immunoreactive (VGluT
      IR) terminals, were significantly larger than dendritic spines innervated by
      VGluT-IR terminals alone. Under electron microscopy, glutamatergic synapses on
      the dendritic spines were located with TH-IR terminals and displayed longer
      postsynaptic density. In addition, these synapses were more perforated than those
      on dendritic spines lacking innervated TH-IR terminals. These results
      demonstrated that dopaminergic axons were biased to a target and preferred to
      innervate dendritic spines with hyperactive and high-efficacy glutamatergic
      synapses in the striatum.

PMID- 23010311
TI  - A preliminary study of alterations in default network connectivity in post
      traumatic stress disorder patients following recent trauma.
AB  - This study used resting-state functional magnetic resonance imaging (fMRI) to
      investigate whether functional connectivity is altered in people developing post
      traumatic stress disorder (PTSD) following recent trauma. Sixty-two participants
      who had experienced recent acute traumatic events underwent a 7.3 min resting
      fMRI scan within 2 days post accident. Of these, 22 participants were diagnosed
      with PTSD within 1 to 6 months. Nineteen age- and sex-matched subjects without
      PTSD were selected as the trauma-exposed control group. Posterior cingulate
      cortex connectivity was determined from 17 PTSD patients and 15 control subjects
      by investigating synchronic low-frequency fMRI signal fluctuations using a
      temporal correlation method. To assess the relationship between PTSD symptom
      severity and PCC connectivity, the contrast image representing areas correlated
      with the PCC was correlated with the 17 PTSD subjects' Clinician Administered
      PTSD Scale (CAPS) scores at diagnosis. Compared with the control group, PTSD
      patients exhibited decreased functional connectivity in the right lingual and
      right middle temporal gyri, and left lingual/posterior cingulate cortex. The left
      inferior temporal gyrus, right middle temporal gyrus, left middle temporal
      gyrus/insula, left medial frontal lobe/anterior cingulate cortex, and right
      medial frontal gyrus also showed increased connectivity within two days post
      accident. A negative correlation was found between PCC connectivity and CAPS
      scores in the left medial prefrontal cortex (mPFC). These results suggest that
      patients who develop PTSD exhibit different resting-state patterns of neuronal
      activity following recent trauma. Abnormal FC of mPFC may be a major risk factor
      predisposing patients to the development of PTSD.

PMID- 23010312
TI  - Protective effects of hydrogen-rich saline in a rat model of permanent focal
      cerebral ischemia via reducing oxidative stress and inflammatory cytokines.
AB  - Hydrogen gas (H(2)) as a new medical gas exerts organ-protective effects through
      regulating oxidative stress, inflammation and apoptosis. In contrast to H(2),
      hydrogen-rich saline (HS) may be more suitable for clinical application. The
      present study was designed to investigate whether HS can offer a neuroprotective
      effect in a rat model of permanent focal cerebral ischemia and what mechanism(s)
      underlies the effect. Sprague-Dawley rats were subjected to permanent focal
      cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO).
      Different doses of HS or normal saline were intraperitoneally administered at
      5min after pMCAO or sham operation followed by injections at 6h, 12h and 24h.
      Here, we found that HS treatment significantly reduced infarct volume and
      improved neurobehavioral outcomes at 24h, 48h and 72h after pMCAO operation in a
      dose-dependent manner (P<0.05). Moreover, we found that HS treatment dose
      dependently increased the activities of endogenous antioxidant enzymes (SOD and
      CAT) as well as decreased the levels of oxidative products (8-iso-PGF2alpha and
      MDA) and inflammatory cytokines (TNF-alpha and HMGB1) in injured ipsilateral
      brain tissues at 6h, 12h and 24h after pMCAO operation (P<0.05). Thus, hydrogen
      rich saline dose-dependently exerts a neuroprotective effect against permanent
      focal cerebral ischemia, and its beneficial effect is at least partially mediated
      by reducing oxidative stress and inflammation. Molecular hydrogen may be an
      effective therapeutic strategy for stroke patients.

PMID- 23010313
TI  - Testosterone has sublayer-specific effects on dendritic spine maturation mediated
      by BDNF and PSD-95 in pyramidal neurons in the hippocampus CA1 area.
AB  - Testosterone has a number of important physiological roles and acts on peripheral
      target tissues and the central nervous system. Testosterone exerts many of its
      effects through the androgen receptor (AR). ARs are widely distributed in nervous
      tissues and particularly strongly expressed in hippocampal CA1 pyramidal neurons,
      which play critical roles in spatial memory tasks. Dendritic spines are
      specialized to receive synaptic inputs, and a change in spine morphology is
      correlated with the strength and maturity of each synapse. In this study, we used
      thy1-GFP transgenic male adult mice to analyze the morphology of dendritic spines
      in the hippocampal CA1 area. Gonadectomy (GDX) induced aberrant morphologies with
      less mushroom-type and more stubby- and thin-type spines in the proximal part of
      the stratum radiatum after two weeks. These morphological changes were also
      observed in the distal part of the stratum radiatum, whereas there was no change
      in the stratum lacunosum-moleculare after GDX. Testosterone replacement in GDX
      mice recovered the changes in spine types to those found in controls. To
      determine the mechanism of the testosterone-dependent morphological changes, we
      examined expression of brain-derived neurotrophic factor (BDNF) and its
      downstream target post-synaptic density protein 95 (PSD-95). GDX induced a
      significant decrease in the protein levels of BDNF and PSD-95 in the CA1 area,
      which were prevented by testosterone replacement. These findings reveal a novel
      role of testosterone in prevented the differential response properties of spine
      maturation in sublayers of dendritic spines in the CA1 area via the actions of
      BDNF and PSD-95.

PMID- 23010314
TI  - Action-related semantic content and negation polarity modulate motor areas during
      sentence reading: an event-related desynchronization study.
AB  - Our study evaluated motor cortex involvement during silent reading of sentences
      referring to hand actions. We aimed at defining whether sentential polarity
      (affirmative vs. negative) would modulate motor cortex activation using the event
      related desynchronization (ERD) analysis of the mu rhythm. Eleven healthy
      volunteers performed a reading task involving 160 sentences (80 affirmative: 40
      hand-related, 40 abstract; 80 negative: 40 hand-related, 40 abstract). After
      reading each sentence, subjects had to decide whether the verb was high or low
      frequency in Italian. Electroencephalographic (EEG) activity was recorded with 32
      surface electrodes and mu ERD analyses were performed for each subject. Hand
      action related sentences induced a greater mu ERD over the left premotor and
      motor hand areas compared to abstract sentences. Mu ERD was greater and
      temporally delayed when the hand-related verbs were presented in the negative
      versus affirmative form. As predicted by the "embodied semantic" theory of
      language understanding, motor areas were activated during sentences referring to
      hand actions. In addition, motor cortex activation was larger for negative than
      affirmative motor sentences, a finding compatible with the hypothesis that
      comprehension is more demanding in the specific case of motor content negation.

PMID- 23010315
TI  - The effect of flow configuration on hydrodynamic stresses and dispersion of low
      density rigid aggregates.
AB  - The effect of flow configuration on the distribution of internal stresses in
      rigid colloidal aggregates was investigated numerically for cluster-cluster
      aggregates with fractal dimensions ranging from 1.7 to 2.3. Stokesian dynamics
      was used to evaluate the hydrodynamic force on each monomer, while the internal
      intermonomer interactions were calculated by applying force and torque balances
      on each primary particle. The examined two-dimensional flows were characterised
      by a mixing index lambda, that ranged from 0 (rotation) to 1 (elongation), with
      pure shear flow at lambda=0.5. Two regimes of motion were identified: for lambda
      > or approximately equal to 0.6 aggregates rotate continuously, whereas at higher
      values (lambda or approximately equal to 0.7) they reach a stationary orientation
      with respect to the flow field. A transition region, in which only some of the
      aggregates reach the stationary condition, separates the two regimes. The
      stationary regime appeared more favourable to induce breakage or restructuring,
      because in this case the generated internal stresses are sustained in time, while
      in the rotational regime they vary cyclically. We showed that the greater
      effectiveness of elongation with respect to shear can be explained by relating
      the condition of breakage to the time-averaged value of the internal stress
      rather than to the instantaneous value. By exploiting this relationship, the
      information on the viscous stress required to break or restructure an aggregate
      in a particular flow configuration can be easily extended to a different flow
      type.

PMID- 23010316
TI  - Impact of ionic strength of growth on the physiochemical properties, structure,
      and adhesion of Listeria monocytogenes polyelectrolyte brushes to a silicon
      nitride surface in water.
AB  - The adhesion energies between pathogenic Listeria monocytogenes EGDe to a model
      surface of silicon nitride were quantified using atomic force microscopy (AFM) in
      water for cells grown in pure media (as the control) and in media of four
      different ionic strengths of added NaCl (IS of 0.05 M, 0.1 M, 0.3 M and 0.5 M
      NaCl). The physiochemical properties of L. monocytogenes EGDe surface brushes
      were shown to have a strong influence on the adhesion of the microbe to the
      silicon nitride surface. The transitions in the adhesion energies, physiochemical
      properties, and the structure of bacterial surface polyelectrolyte brushes were
      observed for the cells grown in the media of 0.1M added NaCl. Our results
      suggested that the highest long-range electrostatic repulsion which was partially
      balanced by the Liftshitz-van der Waals attraction for the cells grown at 0.1M
      was responsible for the highest energy barrier to adhesion for these cells as
      predicted by the soft-particle analysis of DLVO theory and the lower adhesion
      measured by AFM.

PMID- 23010317
TI  - Interaction of human serum albumin with monofluorinated phospholipid monolayers.
AB  - In this work the interaction between human serum albumin (HSA) and a
      monofluorinated phospholipid, 1-palmitoyl-2-[16-fluoropalmitoyl
      phosphatidylcholine] (F-DPPC), was studied by using Langmuir monolayer and
      Brewster angle microscopy (BAM) techniques. Different amounts of F-DPPC were
      spread on a previously formed HSA monolayer located at the air/water interface at
      25 degrees C and the mixed monolayers thus obtained showed the existence of a
      liquid expanded-liquid condensed (LE-LC) phase transition (at 14 mN/m),
      attributed to the pure F-DPPC monolayer, coexisting with a second transition (at
      22-24 mN/m) corresponding to the protein conformational change from an unfolded
      state to another in "loops" configuration. Relative thickness measurements
      recorded during the compression of the mixed monolayers showed the existence of
      an "exclusion" surface pressure (pi(exc)), above which the protein is squeezed
      out the interface, but not totally. BAM images reveal that some protein molecules
      in a packed "loops" configuration remain at the interface at surface pressures
      higher than the "exclusion" surface pressure. The application of the Defay-Crisp
      phase rule to the phase diagram of the F-DPPC/HSA system can explain the
      existence of certain regions of surface pressure in which the mixed monolayer
      components are miscible, as well as those others that they are immiscible.

PMID- 23010318
TI  - High ethanol sensitivity of palladium/TiO2 nanobelt surface heterostructures
      dominated by enlarged surface area and nano-Schottky junctions.
AB  - TiO(2) nanobelts were prepared by the hydrothermal growth method. The surface of
      the nanobelts was coarsened by selective acid corrosion and functionalized with
      Pd catalyst particles. Three nanobelt samples (TiO(2) nanobelts, surface
      coarsened TiO(2) nanobelts and Pd nanoparticle/TiO(2) nanobelt surface
      heterostructures) were configured as gas sensors and their sensing ability was
      measured. Both the surface-coarsened nanobelts and the Pd nanoparticle-decorated
      TiO(2) nanobelts exhibited dramatically improved sensitivity to ethanol vapor. Pd
      nanoparticle-decorated TiO(2) nanobelts with surface heterostructures exhibited
      the best sensitivity, selectivity, working temperature, response/recovery time,
      and reproducibility. The excellent ethanol sensing performance is attributed to
      the large surface area and enhancement by Schottky barrier-type junctions between
      the Pd nanoparticles and TiO(2) nanobelts.

PMID- 23010319
TI  - Synthesis of nanostructured magnetic photocatalyst by colloidal approach and
      spray-drying technique.
AB  - Nanostructured particles with a magnetic core and a photocatalytic shell are very
      interesting systems for their properties to be magnetically separable (and so
      reusable) in photocatalytic water depuration implant. Here, a robust, low time
      consuming, easily scale up method to produce Fe(3)O(4)/SiO(2)/TiO(2) hierarchical
      nanostructures starting from commercial precursors (i.e. Fe(3)O(4), SiO(2)) by
      employing a colloidal approach (i.e. heterocoagulation) coupled with the spray
      drying technique is presented. In particular, a self-assembled layer-by-layer
      methodology based on the coagulation of dissimilar colloidal particles was
      applied. First, a passive layer of silica (SiO(2), amorphous) was created on
      magnetite in order to avoid detrimental phenomena arising from the direct contact
      between magnetite and titania, then the deposition of titania onto silica-coated
      magnetite was promoted. TiO(2), SiO(2) and Fe(3)O(4) nanosols were characterized
      in terms of zeta potential, optimized and a self-assembled layer-by-layer
      approach was followed in order to promote the heterocoagulation of silica onto
      magnetite surface and of titania onto silica coated magnetite. Once optimized the
      colloidal route, the mixture was then spray-dried to obtain a granulated powder
      with nano-scale reactivity, easier to handle and re-disperse in comparison to
      starting nanopowders with the same surface properties. The nanostructured
      particles have been characterized by different techniques such as SEM, TEM, XDR
      and their magnetic properties have been investigated. Moreover, preliminary
      photocatalytic texts have been performed.

PMID- 23010320
TI  - Relation between the gel structure and the mobility of tracers in globular
      protein gels.
AB  - Diffusion of fluorescent-labeled dextran with different molecular weights was
      investigated in beta-lactoglobulin (beta-lg) solutions and gels over a wide range
      of salt and protein concentrations at pH 7 by combining confocal laser scanning
      microscope (CLSM) with fluorescence recovery after photobleaching (FRAP). Effects
      of the protein concentration, the salt concentration and the tracer size were
      investigated in detail. Diffusion in turbid heterogeneous gels formed at 0.2M
      NaCl depended weakly on the probe size and the protein concentration and remained
      close to that in unheated solutions. A strong decrease of the diffusion
      coefficient with increasing tracer size and protein concentration was observed in
      more homogeneous gels formed at lower salt concentrations. Larger dextran chains
      were trapped in transparent gels formed at NaCl concentration below 0.1M. The
      present investigation complements an earlier study of tracer diffusion of larger
      spherical probes in beta-lg gels using multi-particle tracking.

PMID- 23010321
TI  - TiO2/activated carbon fibers photocatalyst: effects of coating procedures on the
      microstructure, adhesion property, and photocatalytic ability.
AB  - In order to more easily separate TiO(2) photocatalyst from the treated
      wastewater, TiO(2) film was immobilized on the surface of activated carbon fibers
      (ACFs) by employing two kinds of coating procedures, dip-coating, and
      hydrothermal treatment. The effects of coating procedures on microstructure of
      TiO(2)-coated ACFs (TiO(2)/ACFs), such as morphology, porous property, crystal
      structure, and light absorption characteristics were investigated in detail. The
      adhesion property between TiO(2) film and ACFs was evaluated by ultrasonic
      vibration, and the photocatalytic activity of TiO(2)/ACFs was tested by the
      photocatalytic decoloration of methylene blue solution. The results show that
      hydrothermal treatment presented many advantages to obtain high-performance
      TiO(2)/ACFs photocatalyst in comparison with dip-coating. Hydrothermal treatment
      could improve the binding property between TiO(2) films and ACFs, which endowed
      the as-obtained TiO(2)/ACFs photocatalyst with improved reusable performance, and
      TiO(2)/ACFs synthesized by hydrothermal treatment presented higher photocatalytic
      activity.

PMID- 23010322
TI  - Highly concentrated emulsified microemulsions as solvent-free plant protection
      formulations.
AB  - Effective plant protection agents are readily available and well implemented in
      industry. However, delivery to the plant and application on the leaf are
      processes that still need to be optimized. Up to now plant protection
      formulations represent either emulsion or suspension concentrates that often
      contain environmentally harmful organic solvents and/or adjuvants. Emulsified
      microemulsions are hierarchically organized systems comprising emulsion droplets
      that confine a water-in-oil microemulsion. In the present contribution we show
      that emulsified microemulsions prepared from environmentally friendly components
      can be loaded with the plant-protection agent Fenpropimorph(r) up to 48 wt.%
      without organic solvent. The emulsion itself is highly concentrated, containing
      60 wt.% of dispersed phase, and can be readily diluted with water for spraying in
      farming applications. Small-angle X-ray measurements reveal the existence of a
      water-in-Fenpropimorph(r) microemulsion confined inside the emulsion droplets.
      Dynamic light scattering shows that the emulsions prepared are monomodal,
      comprising droplet radii in the hundred nanometer range.

PMID- 23010323
TI  - Relevance of copper transporter 1 for cisplatin resistance in human ovarian
      carcinoma cells.
AB  - Defects in intracellular accumulation of the antitumour drug cisplatin are a
      commonly observed feature in the cells selected for cisplatin resistance. Copper
      transporter 1 (CTR1) has been suggested to play an important role in drug uptake
      and resistance. Here, we describe a detailed investigation of the involvement of
      CTR1 in cisplatin uptake and its relevance for cisplatin resistance using a well
      characterised sensitive/cisplatin-resistant cell line pair: A2780 human ovarian
      carcinoma cell line and its cisplatin-resistant variant A2780cis. A2780cis cells
      showed decreased cisplatin accumulation and lower CTR1 expression compared to
      A2780 cells. Co-incubation with copper sulphate affected neither cisplatin
      accumulation (determined by flameless atomic absorption spectrometry) nor its
      cytotoxicity (determined using an MTT-assay, MTT=3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl-2H-tetrazolium bromide). In both cell lines, CTR1 was localised near the
      nucleus as found using confocal fluorescence microscopy. The steady-state
      localisation of the protein in perinuclear region appears to involve its
      continuous endocytosis from cell surface. In contrast to copper, cisplatin
      exposure had no influence on the sub cellular localisation of CTR1. Co
      localisation between CTR1 and a fluorescent cisplatin analogue labelled with
      carboxyfluorescein-diacetate could be observed in vesicular structures when
      continuous retrieval of the protein from cell membrane was inhibited. Our results
      strongly suggest that CTR1 mediates cisplatin uptake in the cell lines studied.
      Upon its transport across the plasma membrane by CTR1 the platinum drug is likely
      to be internalised along with the protein. Our findings imply that reduced CTR1
      expression accounts for decreased cisplatin accumulation and represents one of
      the determinants of cisplatin resistance in A2780cis cell line.

PMID- 23010324
TI  - Interaction of apo-transferrin with anticancer ruthenium complexes NAMI-A and its
      reduced form.
AB  - NAMI-A i.e. (ImH)[trans-RuCl(4)(DMSO)(Im)] (where Im is imidazole) is a
      ruthenium(III) complex with promising antimetastatic activity, which has been
      classified for II phase clinical trial. In this study, its binding properties
      toward apo-transferrin (apo-Tf) with regard to its hydrolytic and redox behavior
      are systematically investigated by the use of fluorescence spectroscopy. The
      reaction of NAMI-A and its reduced form with apo-Tf is proceeded by formation of
      aqua derivatives and the presence of at least one labile aqua ligand is
      sufficient to form adducts. It is found that presence of bicarbonate is not
      necessary for interaction of studied ruthenium complexes with apo-Tf. The
      calculated association constants for both NAMI-A and its reduced form are very
      similar with the values of 1.28 * 10(4)M(-1) and 1.36 * 10(4)M(-1) at 37  degrees
      C, respectively however, the reduced derivatives reach the equilibrium ca. 8-10
      times slower. The percentage of ruthenium content in protein fractions separated
      from protein-unbounded ruthenium by using FPLC (fast protein liquid
      chromatography) method is rather high and depends on redox state of the complex,
      for most samples is found higher for reduced species.

PMID- 23010325
TI  - Syntheses and in vitro antitumor activities of ferrocene-conjugated Arg-Gly-Asp
      peptides.
AB  - Ferrocene (Fc) and its conjugates have attracted considerable attention in recent
      years due to their unique electrochemical behavior and significant biological
      activities such as antitumor, antimalarial, and antifungal. Arg-Gly-Asp (RGD)
      containing peptides, because of their selective binding to integrins which are
      highly expressed in tumor-induced angiogenesis, play a key role in cancer
      targeted therapy. In this study, Fc-RGD and Fc-Am-RGD (Fc: ferrocenoyl; Am: 6
      aminohexanoic acid) conjugates were synthesized, and the antitumor activities in
      vitro were investigated. The cell uptake of the conjugates by B16 murine melanoma
      cells was measured using HPLC-electrochemical method. The antitumor activities of
      the conjugates were also evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) and flow cytometric measurements. The
      experimental results revealed that Fc-RGD and Fc-Am-RGD exhibit more effective
      antitumor activities than their parent compounds RGD and Fc-COOH. Moreover, it is
      found that Fc-Am-RGD yields the lowest IC(50) values of 5.2 +/- 1.4 MUM toward
      B16 cells. The HPLC-electrochemical studies confirmed that the insertion of
      flexible alkyl spacer Am between Fc and RGD significantly increases the cell
      uptake toward B16 cells and consequently improves the antitumor activity. Our
      results suggest that Fc-RGD and Fc-Am-RGD conjugates are potential candidates for
      cancer treatment.

PMID- 23010326
TI  - Dual role of Cu2+ ions on the aggregation and degradation of soluble Abeta
      oligomers and protofibrils investigated by fluorescence spectroscopy and AFM.
AB  - The neuropathological character of copper(II) ions (Cu(2+)) upon interaction with
      soluble human amyloid-beta(1-42) that subsequently generates senile plaques
      and/or reactive oxygen species (ROS) is considered as one of the very important
      features of Alzheimer's disease. The present study carried out by using
      fluorescence spectroscopy and atomic-force microscopy (AFM) indeed confirms the
      dual role played by Cu(2+), namely as mediator of protein aggregation and as
      generator of ROS leading to irreversible protein alteration, which most likely
      involve two distinct copper-binding sites. The AFM investigations clearly
      evidence the copper-induced aggregation of Abeta oligomers and protofibrils,
      while comparative fluorescence measurements with copper and zinc reveals the
      crucial involvement of redox-active copper in the generation of Abeta-cross
      linked structures.

PMID- 23010328
TI  - Amino acid-based tweezers: the role of turn-like conformation in the binding of
      copper(II).
AB  - The importance of turn-like peptide conformation for the copper(II) binding has
      been revealed by the synthesis of simple amino acid-based tweezers and the study
      of their interaction with copper(II). Amino acids Phe, Leu, Val, Ala and Gly were
      bridged through their C-terminuses with conformationally constrained motif, cis
      enediyne moiety ((Z)-octa-4-en-2,6-diyne-1,8-diamine). The interaction of
      prepared diamine ligands with copper(II) was studied by means of potentiometric
      titrations, UV-visible and EPR spectroscopic and mass spectrometric techniques.
      All ligands interact efficiently with copper(II) and form complexes of 1:1
      stoichiometry differing in the protonation state of the ligand. LCu(2+) species
      were found predominant at pH<6.5, with log K* ranging from -8.06 to -6.65, while
      at higher pH deprotonation occurred, giving rise to LH(-1)Cu(+) complexes or LH(
      2)Cu complex for the phenylalanine-related ligand. An additional species, LH(
      3)Cu(-) were found at pH>9 for the valine- and alanine-related ligands,
      respectively. Comparing stability of studied complexes with those reported in
      previous work revealed that ligands effectively emulate properties of copper(II)
      binding peptides. Based on the results obtained in this work it can be concluded
      that structural rigidity significantly enhances coordination properties of the
      ligand, thus conforming importance of the turn-like peptide conformation for the
      copper(II) binding.

PMID- 23010329
TI  - Effect of quaternary structure change on the low-lying electronic states of the
      ferrous heme in deoxy-Hb studied by multi-frequency EPR.
AB  - The effect of the quaternary structure change in deoxy-Hb on the electronic
      states of the ferrous high-spin heme was studied by multi-frequency electron
      paramagnetic resonance (MFEPR). We used a single-pass transmission-type EPR at 70
      220 GHz and at 1.5K. We compared the EPR spectra of deoxy-Hb at high pH with
      those at low pH and in the presence of the allosteric effectors, such as inositol
      hexaphosphate (IHP). Our EPR results imply that the low-lying electronic states
      of the ferrous heme in deoxy-Hb could be altered by the changes in the heme
      geometry, which might be caused by the quaternary structure change in Hb. We also
      measured EPR spectra of deoxy FeMg hybrid Hb to clarify the difference between
      alpha and beta hemes at low pH with IHP. The additional complicated resonance
      branches appeared in deoxy-Hb as well as in deoxy FeMg hybrid Hbs at low pH with
      IHP may reflect the energy states of the ferrous high-spin heme correlated with
      the low oxygen affinity state. The magnetic moment of the lowest excited state of
      the alpha heme seems to be different from that of the beta heme in the low oxygen
      affinity state.

PMID- 23010327
TI  - Biochemical and structural characterization of recombinant human serum
      transferrin from rice (Oryza sativa L.).
AB  - The Fe(3+) binding protein human serum transferrin (hTF) is well known for its
      role in cellular iron delivery via the transferrin receptor (TFR). A new
      application is the use of hTF as a therapy and targeted drug delivery system for
      a number of diseases. Recently, production of hTF in plants has been reported;
      such systems provide a relatively inexpensive, animal-free (eliminating potential
      contamination by animal pathogens) method to produce large amounts of recombinant
      proteins for such biopharmaceutical applications. Specifically, the production of
      Optiferrin (hTF produced in rice, Oryza sativa, from InVitria) has been shown to
      yield large amounts of functional protein for use in culture medium for cellular
      iron delivery to promote growth. In the present work we describe further
      purification (by gel filtration) and characterization of hTF produced in rice
      (purified Optiferrin) to determine its suitability in biopharmaceutical
      applications. The spectral, mass spectrometric, urea gel and kinetic analysis
      shows that purified Optiferrin is similar to recombinant nonglycosylated N-His
      tagged hTF expressed by baby hamster kidney cells and/or serum derived
      glycosylated hTF. Additionally, in a competitive immunoassay, iron-loaded
      Optiferrin is equivalent to iron-loaded N-His hTF in its ability to bind to the
      soluble portion of the TFR immobilized in an assay plate. As an essential
      requirement for any functional hTF, both lobes of purified Optiferrin bind Fe(3+)
      tightly yet reversibly. Although previously shown to be capable of delivering
      Fe(3+) to cells, the kinetics of iron release from iron-loaded OptiferrinTM/sTFR
      and iron-loaded N-His hTF/sTFR complexes differ somewhat. We conclude that the
      purified Optiferrin might be suitable for consideration in biopharmaceutical
      applications.

PMID- 23010330
TI  - Copper complexation of methanobactin isolated from Methylosinus trichosporium
      OB3b: pH-dependent speciation and modeling.
AB  - Methanobactins are copper-binding ligands produced by aerobic methanotrophic
      microorganisms. A quantitative understanding of their potential role in
      methanotrophic copper acquisition requires the investigation of their copper
      complexes under relevant pH conditions. In this study, a chemical speciation
      model describing the pH-dependence of copper binding and the formation of the
      different complexes by methanobactin (mb) is released by Methylosinus
      trichosporium OB3b was developed. Potentiometric and spectrophotometric
      titrations of the free ligand indicated the presence of four protonation sites
      consistent with the molecular structure of methanobactin. Metal titrations
      revealed a distinct pH-dependence of copper binding to methanobactin between pH 5
      and 8. Based on evidence from size-exclusion chromatography coupled to
      inductively coupled plasma mass spectrometry (ICP-MS), the copper binding was
      quantitatively described with three different types of copper-methanobactin
      complexes which can additionally undergo protonation reactions. The high affinity
      observed upon initial copper additions resulted from the predominant occurrence
      of copper-methanobactin dimer complexes, mb(2)H(4)Cu and mb(2)H(3)Cu with log K
      values of 58 and 52, respectively. With increasing copper to methanobactin
      ratios, methanobactin bound copper as monomers, mbHCu (log K=25) and mbCu (log
      K=18), whereas at elevated copper activities methanobactin was able to bind two
      copper ions (mbHCu(2) and mbCu(2)). Model calculations based on the fitted
      complexation constants suggest that in natural systems, copper-methanobactin
      complexes are mostly present as monomers.

PMID- 23010331
TI  - The acute toxicity of iron and copper: biomolecule oxidation and oxidative damage
      in rat liver.
AB  - The transition metals iron (Fe) and copper (Cu) are needed at low levels for
      normal health and at higher levels they become toxic for humans and animals. The
      acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g)
      that received ip 0-60 mg/kg FeCl(2) or 0-30 mg/kg CuSO(4). Dose and time
      responses were determined for spontaneous in situ liver chemiluminescence,
      phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants.
      The doses linearly defined the tissue content of both metals. Liver
      chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with
      half maximal responses at contents (C(50%)) of 110 MUgFe/g and 42 MUgCu/g liver,
      and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid
      peroxidation increased 4 and 1.8 times with C(50%) of 118 MUg Fe/g and 45 MUg
      Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe
      with C(50%) at 113 MUg Fe/g and 1.2 times for Cu with 50 MUg Cu/g and t(1/2) of
      4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate
      of free radical reactions and produced oxidative damage. A similar free radical
      mediated process, through the formation HO(*) and RO(*) by a Fenton-like
      homolytic scission of H(2)O(2) and ROOH, seems to operate as the chemical
      mechanism for the liver toxicity of both metals.

PMID- 23010332
TI  - Metal-binding domains and the metal selectivity of the vanadium(IV)-binding
      protein VBP-129 in blood plasma.
AB  - Ascidians are well known to accumulate extremely high levels of vanadium in their
      blood cells. Several key proteins related to vanadium accumulation and
      physiological function have been isolated from vanadium-rich ascidians. Of these,
      vanadium(IV)-binding protein-129 (VBP-129) is a unique protein that has been
      identified from the blood plasma of an ascidian Ascidia sydneiensis samea, but
      its metal binding domains are not known. In this study, several deletion and
      point mutants of VBP-129 were generated, and their metal binding abilities were
      assessed by immobilized metal ion affinity chromatography (IMAC) and electron
      spin resonance spectroscopy (ESR). The internal partial protein, VBP-Int41, did
      not bind to V(IV), but the two constructs, VBP-N52 and VBP-Int55, added with
      additional 11 or 14 neighboring amino acids bound to V(IV). Mutations for
      cysteine-47 and lysine-50 in VBP-Int55 diminished V(IV)-binding in VBP-Int55,
      suggesting that these amino acid residues play important roles in binding V(IV).
      ESR titration analysis revealed that VBP-129, VBP-N52 and VBP-Int55 could bind to
      6, 3 and 2 V(IV) ions, respectively. ESR spectrum analysis indicated a N(2)O(2)
      coordination geometry, which is similar to vanabins. The cysteines may contribute
      to the maintenance of the three-dimensional structure that is necessary for
      binding V(IV) ions. VBP-129 did not have a V(V)-reductase activity, as expected
      from its tissue localization in blood plasma. This study provided the evidences
      that VBP-129 possesses V(IV)-binding domains that make a similar coordination to
      V(IV) as those by vanabins but VBP-129 acts solely as a V(IV)-chaperon in blood
      plasma.

PMID- 23010333
TI  - Behavioral consequences of unilateral inferior colliculus lesions in the rat.
AB  - This study was carried out to determine the behavioral sensitivity to sound of
      rats with unilateral lesions of inferior colliculus (IC) located ipsilateral or
      contralateral to the projection pathway from one ear. Absolute thresholds for the
      detection of a broad-band noise burst were compared for rats with a profound
      conductive hearing loss in one ear and a lesion placed either ipsilateral or
      contralateral to the normally functioning ear. The rats were trained to make
      withdrawal responses to avoid a shock when they detected the presence of a noise
      burst. Sound pressure level was systematically lowered to obtain psychophysical
      curves from which absolute thresholds could be determined. Complete lesions of
      the contralateral IC resulted in substantial elevations in absolute threshold
      relative to normal whereas equivalent lesions of the ipsilateral IC produced
      relatively little elevation. In neither case did unilateral destruction of the IC
      produce a total inability to respond to sound. Contralateral IC lesions that
      included the dorsal nucleus of the lateral lemniscus (DNLL) produced a
      significantly greater elevation in behavioral thresholds than complete lesions
      limited to the IC. The results indicate a predominance of the contralateral over
      the ipsilateral pathway to IC for maintaining normal thresholds. They also
      indicate that other pathways that bypass the IC are likely involved in detecting
      the presence of a sound.

PMID- 23010334
TI  - Parvalbumin immunoreactivity in the auditory cortex of a mouse model of
      presbycusis.
AB  - Age-related hearing loss (presbycusis) affects ~35% of humans older than sixty
      five years. Symptoms of presbycusis include impaired discrimination of sounds
      with fast temporal features, such as those present in speech. Such symptoms
      likely arise because of central auditory system plasticity, but the underlying
      components are incompletely characterized. The rapid spiking inhibitory
      interneurons that co-express the calcium binding protein Parvalbumin (PV) are
      involved in shaping neural responses to fast spectrotemporal modulations. Here,
      we examined cortical PV expression in the C57bl/6 (C57) mouse, a strain commonly
      studied as a presbycusis model. We examined if PV expression showed auditory
      cortical field- and layer-specific susceptibilities with age. The percentage of
      PV-expressing cells relative to Nissl-stained cells was counted in the anterior
      auditory field (AAF) and primary auditory cortex (A1) in three age groups: young
      (1-2 months), middle-aged (6-8 months) and old (14-20 months). There were
      significant declines in the percentage of cells expressing PV at a detectable
      level in layers I-IV of both A1 and AAF in the old mice compared to young mice.
      In layers V-VI, there was an increase in the percentage of PV-expressing cells in
      the AAF of the old group. There were no changes in percentage of PV-expressing
      cells in layers V-VI of A1. These data suggest cortical layer(s)- and field
      specific susceptibility of PV+ cells with presbycusis. The results are consistent
      with the hypothesis that a decline in inhibitory neurotransmission, particularly
      in the superficial cortical layers, occurs with presbycusis.

PMID- 23010335
TI  - Binaural release from masking in forward-masked intensity discrimination:
      evidence for effects of selective attention.
AB  - In a forward-masked intensity discrimination task, we manipulated the perceived
      lateralization of the masker via variation of the interaural time difference
      (ITD). The maskers and targets were 500 Hz pure tones with a duration of 30 ms.
      Standards of 30 and 60 dB SPL were combined with 60 or 90 dB SPL maskers. As
      expected, the presentation of a forward masker perceived as lateralized to the
      other side of the head as the target resulted in a significantly smaller
      elevation of the intensity difference limen than a masker lateralized
      ipsilaterally. This binaural release from masking in forward-masked intensity
      discrimination cannot be explained by peripheral mechanisms because varying the
      ITD leaves the neural representation in the monaural channels (i.e., in the
      auditory nerve) unaltered. Instead, our results are compatible with the
      assumption that lateralization differences between masker and target promote
      object segregation and therefore facilitate object-based selective attention to
      the target.

PMID- 23010336
TI  - One-stage vs. two-stage BAHA implantation in a pediatric population.
AB  - OBJECTIVES: BAHA implantation surgery in a pediatric population is usually done
      in two-stage surgeries. This study aims to evaluate the safety and possible
      superiority of the one-stage over the two-stage BAHA implantation and which one
      would be the best standard of care for our pediatric patients. METHODS: A
      retrospective chart review of 55 patients operated in our tertiary care
      institutions between 2005 and 2010 was conducted. The actual tendency in our
      institutions, applied at the time of the study, is to perform a one-stage surgery
      for all operated patients (pediatric and adult), except for patients undergoing
      translabyrinthine surgeries for cerebellopontine tumor excision. These patients
      indeed had a two-stage insertion. 26 patients underwent one-stage surgery (group
      I) while 29 patients had a two-stage (group II) BAHA insertion. A period of 4
      months was allowed for osseointegration before BAHA processor fitting. As for the
      safety assessment of the one-stage surgery, we compared both groups regarding the
      incidence and severity (minor, moderate and major) of encountered complications,
      as well as the operating time and follow-up. The operating time of the two-stage
      surgery includes the time of the first and of the second stage. RESULTS: The mean
      age at surgery was 8.5 years old for the group I and 50 years old for the group
      II patients. There was no difference in the incidence of minor (p=0.12), moderate
      (p=0.41) nor severe (p=0.68) complications between groups I and II. Two cases of
      traumatic extrusion were noted in the group I. Furthermore, the one-stage BAHA
      implantation requests a significantly lower operating time (mean: 54 [32-100]
      min) than the two-stage surgery (mean: 79 [63-148] min) (p=0.012). All pediatric
      cases of BAHA insertion were performed in a one day surgery. The mean
      postoperative follow-up was 114 and 96 weeks for groups I and II respectively
      (p=0.058). CONCLUSIONS: One-stage BAHA insertion surgery in the pediatric
      population is a reliable, safe and efficient therapeutic option that allows a
      good result in a significantly lower operating time compared to the two-stage
      insertion and is achieved in a one day surgery. It could therefore be considered
      as a standard of care for pediatric patients.

PMID- 23010337
TI  - Associations between friends' disordered eating and muscle-enhancing behaviors.
AB  - Dieting, unhealthy weight control and muscle-enhancing behaviors are common among
      adolescents: friends are a probable source of influence on these behaviors. The
      present study uses data provided by nominated friends to examine associations
      between friends' disordered eating and muscle-enhancing behaviors and
      participants' own behaviors in a diverse sample of American youth. Male and
      female adolescents (mean age = 14.4) completed surveys and identified their
      friends from a class roster; friends' survey data were then linked to each
      participant. Participants (N = 2126) who had at least one nominated friend were
      included in the analytic sample. Independent variables were created using the
      same weight control and muscle-enhancing behaviors reported by nominated friends,
      and were used in logistic regression models to test associations between
      participants' and their friends' behaviors, stratified by gender. Results
      indicated that dieting, disordered eating and muscle-enhancing behaviors were
      common in this sample, and selected friends' behaviors were associated with the
      same behaviors in participants. For example, girls whose friends reported extreme
      weight control behaviors had significantly greater odds of using these behaviors
      than girls whose friends did not report these same behaviors (OR = 2.39). This
      research suggests that friends' weight- and shape-related behaviors are a feature
      of social relationships, and is the first report demonstrating these associations
      for muscle-enhancing behaviors. Capitalizing on the social element may be
      important to the development of increasingly effective intervention and
      prevention programs.

PMID- 23010338
TI  - Neighborhood poverty, park use, and park-based physical activity in a Southern
      California city.
AB  - A rich literature indicates that individuals of lower socio-economic status
      engage in less leisure time physical activity than individuals of higher socio
      economic status. However, the source of the difference is believed to be, in
      part, due to differential access to resources that support physical activity.
      However, it has not been shown as to whether equal access to parks can mitigate
      differences in leisure time physical activity. Using systematic direct
      observation, we quantified physical activity in neighborhood parks in a large
      Southern California city located in areas with high, medium, and a low percentage
      of households in poverty. We documented how neighborhood parks are managed and
      programmed and also interviewed both a sample of park users and a random sample
      of households within a mile radius of the parks. We found that parks are used
      less in high-poverty areas compared to medium- and low-poverty area parks, even
      after accounting for differences in size, staffing, and programming. The
      strongest correlates of park use were the number of part time staff, the number
      of supervised and organized programs, and knowing the park staff. Perceptions of
      safety were not relevant to park use among those interviewed in the park, however
      it had a small relationship with reported frequency of park use among local
      residents. Among park users, time spent watching electronic media was negatively
      correlated with the frequency of visiting the park. Future research should test
      whether increasing park staffing and programming will lead to increased park use
      in high-poverty neighborhoods.

PMID- 23010339
TI  - A pilot randomised controlled trial in intensive care patients comparing 7 days'
      treatment with empirical antibiotics with 2 days' treatment for hospital-acquired
      infection of unknown origin.
AB  - BACKGROUND: Management of cardiac intensive care unit (ICU) sepsis is complicated
      by the high incidence of systemic inflammatory response syndrome, which mimics
      sepsis but without an infective cause. This pilot randomised trial investigated
      whether or not, in the ICU, 48 hours of broad-spectrum antibiotic treatment was
      adequate to safely treat suspected sepsis of unknown and unproven origin and also
      the predictive power of newer biomarkers of sepsis. OBJECTIVE: The main objective
      of this pilot study was to provide preliminary data on the likely safety and
      efficacy of a reduced course of antibiotics for the treatment of ICU infections
      of unknown origin. DESIGN: A pilot, single-centre, open-label randomised trial.
      SETTING: This study was carried out in the ICU of a tertiary heart and chest
      hospital. PARTICIPANTS: Patients being treated within the ICU were recruited into
      the trial if the intensivist was planning to commence antibiotics because of
      evidence of systemic inflammatory response syndrome and a strong suspicion of
      infection but there was no actual known source for that infection. INTERVENTIONS:
      Broad-spectrum antibiotic treatment administered for 48 hours (experimental)
      compared with treatment for 7 days (control). MAIN OUTCOME MEASURES: The primary
      outcome was a composite outcome of the rate of death or initiation of antibiotic
      therapy after the completion of the treatment schedule allocated at
      randomisation. Secondary outcomes included the duration of mechanical ventilation
      and ICU and hospital stay; the incidence of infection with Clostridium difficile
      (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008, or
      methicillin-resistant Staphylococcus aureus (MRSA) (B. S. Weeks & E. Alcamo)
      Jones & Bartlett International Publishers, 2008; resource utilisation and costs
      associated with each of the two pilot arms; the ratio of patients screened to
      patients eligible to patients randomised; the incidence of crossover between
      groups; and the significance of newer biomarkers for sepsis for predicting
      patients' need for further antibiotics. RESULTS: A total of 46 patients were
      recruited into the trial, with 23 randomised to each group. There was no
      significant difference between the two groups in terms of the composite primary
      outcome measure. The risk difference was 0.12 [95% confidence interval (CI) 0.11
      to 0.13; p = 0.3]. In the 2-day group, four patients (17.4%) required further
      antibiotics compared with three (13%) in the 7-day group. Four patients died
      within the trial period and the deaths were not trial related. Patients who died
      during the trial period received no additional antibiotics in excess of their
      trial allocation. There were no documented incidences of MRSA or C. difficile
      infection in either group. No significant differences in adverse events were
      observed between the groups. Key economic findings were mean antibiotic costs per
      patient of L168.97 for the 2-day group and L375.86 for the 7-day group. The
      potential per annum cost saving for the ICU of 2-day treatment was estimated to
      range from L108,140 to L126,060. Patient screening was considered the biggest
      barrier to recruitment. There was no crossover between the two randomised groups.
      Data verification ascertained > 98% accuracy in data collection. Baseline
      procalcitonin was found to be predictive of the composite outcome (death and
      needing further antibiotics) (odds ratio 1.79, 95% CI 1.20 to 2.67; p = 0.005).
      Analysis of baseline procalcitonin also indicated a trend towards it being a
      predictor of restarting antibiotics, with an odds ratio of 1.45 (95% CI 1.04 to
      2.02; p = 0.01). CONCLUSIONS: Data from this pilot study suggest that there could
      be significant benefits of reducing broad-spectrum antibiotic use in the ICU
      without it undermining patient safety, with a potential cost saving in our unit
      of over L100,000 per year. Evidence from this pilot trial is not definitive but
      warrants further investigation using a large randomised controlled trial. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN82694288. FUNDING: This project was
      funded by the NIHR Health Technology Assessment programme and will be published
      in full in Health Technology Assessment; Vol. 16, No. 36. See the HTA programme
      website for further project information.

PMID- 23010340
TI  - Amplatz sheath for cystolithotripsy using Ho: YAG laser in female patients.
AB  - OBJECTIVE: To evaluate the effectiveness of cystoscopic lithotripsy, we performed
      Amplatz sheath technique using Ho: YAG laser. Maheshwari first reported the use
      of an Amplatz sheath in the female urethra in 1998, and Okeke et al reported the
      use of an Amplatz sheath for male patients during cystolithotripsy in 2004. The
      usefulness of the holmium (Ho): yttrium aluminum garnet (YAG) laser lithotripsy
      is widely accepted, even for large bladder calculi. Since then, there have been
      no more reports of using the sheath with an Ho: YAG laser. TECHNICAL
      CONSIDERATIONS: We inserted the Amplatz sheath conversely. Because of the clear
      visualization, we used higher laser settings with 2.5 J * 15 to 20 Hz. RESULTS:
      We experienced 3 female patients that were successfully treated with the Amplatz
      sheath technique using Ho: YAG laser lithotripsy. In these 3 patients, whose
      stone burdens were 4.5, 3.8, and 4.3 cm, they were able to successfully become
      stone-free with surgeries of 74 minutes, 67 minutes, and 58 minutes,
      respectively, with no complications. CONCLUSION: We experienced 3 female patients
      that were successfully treated with the Amplatz sheath technique using Ho: YAG
      laser lithotripsy.

PMID- 23010341
TI  - Presence of metastasis-associated protein 1 in Sertoli cells is required for
      proper contact between Sertoli cells and adjacent germ cells.
AB  - OBJECTIVE: To investigate whether the normal expression of metastasis-associated
      protein 1 (MTA1) in Sertoli cells (SCs) is associated with adjacent germ cells
      (GCs) and to provide the functional relevance of MTA1 in this somatic cell.
      METHODS: The expression pattern of MTA1 in the SCs of impaired human
      spermatogenesis was determined using immunohistochemistry. The effect of the
      depletion of GCs on the expression of MTA1 in isolated SCs was evaluated using
      reverse transcriptase polymerase chain reaction in murine testes treated with
      busulphan. Finally, using multiple assays, the functional investigation of MTA1
      by its specific knockdown was performed in SC-GC co-cultures. RESULTS: SCs were
      negatively immunolabeled in the tubules with impaired spermatogenesis. Depletion
      of murine GCs by treatment with busulphan resulted in a dramatic decrease of the
      MTA1 transcripts level in the isolated SCs on the 15th day of treatment and
      thereafter had totally abolished MTA1 expression by the 30th day of treatment,
      respectively. The addition of isolated round spermatids into SC culture could
      partially elevate MTA1 expression in the latter. Furthermore, MTA1 is crucial to
      maintain the GC nursery function and normal anchoring junction formation in SCs
      because ablation of MTA1 by siRNA induced extensive defects of genes related to
      SC homeostasis. CONCLUSION: We propose a novel role for SC-expressing MTA1, which
      is determined by the presence of surrounding GCs, in mediating the crosstalk
      between SCs and GCs by influencing a broad spectrum of gene changes.

PMID- 23010342
TI  - The journey of women in urology: the perspective of a female urology resident.

PMID- 23010343
TI  - Protective effects of phosphodiesterase-4-specific inhibitor rolipram on acute
      ischemia-reperfusion injury in rat kidney.
AB  - OBJECTIVE: To investigate the effect of Rolipram, a phosphodiesterase-4
      inhibitor, on renal ischemia-reperfusion injury (IRI) in rats. METHODS: Thirty
      rats were divided into 5 different groups of 6 rats. Nothing was done to the
      control group. In the second group, the renal pedicle was clamped for 30 minutes.
      In the third group, 1 mg/kg of Rolipram was given by intraperitoneal injection 30
      minutes before clamping. The fourth group received the same injection when the
      clamp was placed, as did the fifth group 30 minutes after the clamp was opened.
      Clamping time was set at 30 minutes. Twenty-four hours later, nephrectomy was
      performed in all the groups. Half of each kidney was examined
      histopathologically. Levels of biochemical agents, such as malondialdehyde,
      superoxide dismutase, and catalase, were measured in the other half. RESULTS: The
      malondialdehyde (MDA) levels significantly decreased and reached control levels
      in the group in which Rolipram was administered 30 minutes after reperfusion (P =
      .07). The catalase and superoxide dismutase activities obtained from renal
      homogentisates of the ischemia groups were evaluated; there were striking
      increases in tissue levels of these 2 enzymes in the groups in which Rolipram was
      administered during ischemia and 30 minutes after ischemia (P < .001).
      Histopathologically, there was no significant difference in inflammation between
      the Rolipram-administrated groups compared with group 1 (control) and group 2
      (IRI). Tubular necrosis and apoptosis was significantly lower in group 5 than the
      other groups, except group 1 (P < .001). CONCLUSION: We suggest that in surgical
      procedures that can lead to renal IRI, the administration of Rolipram can
      decrease oxidative renal tissue damage and the severe deterioration of renal
      function.

PMID- 23010344
TI  - Preliminary assessment of safety and efficacy in proof-of-concept, randomized
      clinical trial of tanezumab for chronic prostatitis/chronic pelvic pain syndrome.
AB  - OBJECTIVE: To assess the efficacy and safety of tanezumab, a humanized monoclonal
      antibody directed against the pain-mediating neurotrophin, nerve growth factor,
      to treat pain and other symptoms of chronic prostatitis/chronic pelvic pain
      syndrome in a Phase IIa, proof-of-concept clinical trial powered to provide 2
      sided 90% confidence interval around the primary endpoint. METHODS: Patients
      received a single intravenous dose of tanezumab (20 mg) or placebo. The primary
      efficacy endpoint was the change from baseline to week 6 in average daily
      numerical rating scale pain score. The secondary endpoints included the change
      from baseline to week 6 in the National Institutes of Health Chronic Prostatitis
      Symptom Index and urinary symptoms. Safety was also assessed. RESULTS: Overall,
      62 patients were randomized (30 to tanezumab and 32 to placebo). At week 6,
      tanezumab marginally improved the average daily pain (least-squares mean
      difference from placebo -0.47, 90% confidence interval -1.150-0.209) and urgency
      episode frequency (least-squares mean difference from placebo -1.37, 90%
      confidence interval -3.146-0.401). No difference was seen in the National
      Institutes of Health chronic prostatitis symptom index total score or micturition
      frequency at week 6. The most common adverse events were paresthesia and
      arthralgia. The odds of having a >= 30% reduction in pain were 1.75-fold greater
      (90% confidence interval 0.65-4.69) for patients receiving tanezumab versus
      placebo. CONCLUSION: Tanezumab might improve symptoms for some patients with
      chronic prostatitis/chronic pelvic pain syndrome. Although proof of concept was
      not demonstrated in the present study, additional studies with larger populations
      and stricter inclusion criteria according to patient phenotype might identify
      populations in which antinerve growth factor treatment will provide clinical
      benefit.

PMID- 23010345
TI  - Validation of Web-based physical activity measurement systems using doubly
      labeled water.
AB  - BACKGROUND: Online or Web-based measurement systems have been proposed as
      convenient methods for collecting physical activity data. We developed two Web
      based physical activity systems-the 24-hour Physical Activity Record Web (24hPAR
      WEB) and 7 days Recall Web (7daysRecall WEB). OBJECTIVE: To examine the validity
      of two Web-based physical activity measurement systems using the doubly labeled
      water (DLW) method. METHODS: We assessed the validity of the 24hPAR WEB and
      7daysRecall WEB in 20 individuals, aged 25 to 61 years. The order of email
      distribution and subsequent completion of the two Web-based measurements systems
      was randomized. Each measurement tool was used for a week. The participants'
      activity energy expenditure (AEE) and total energy expenditure (TEE) were
      assessed over each week using the DLW method and compared with the respective
      energy expenditures estimated using the Web-based systems. RESULTS: The mean AEE
      was 3.90 (SD 1.43) MJ estimated using the 24hPAR WEB and 3.67 (SD 1.48) MJ
      measured by the DLW method. The Pearson correlation for AEE between the two
      methods was r = .679 (P < .001). The Bland-Altman 95% limits of agreement ranged
      from -2.10 to 2.57 MJ between the two methods. The Pearson correlation for TEE
      between the two methods was r = .874 (P < .001). The mean AEE was 4.29 (SD 1.94)
      MJ using the 7daysRecall WEB and 3.80 (SD 1.36) MJ by the DLW method. The Pearson
      correlation for AEE between the two methods was r = .144 (P = .54). The Bland
      Altman 95% limits of agreement ranged from -3.83 to 4.81 MJ between the two
      methods. The Pearson correlation for TEE between the two methods was r = .590 (P
      = .006). The average input times using terminal devices were 8 minutes and 10
      seconds for the 24hPAR WEB and 6 minutes and 38 seconds for the 7daysRecall WEB.
      CONCLUSIONS: Both Web-based systems were found to be effective methods for
      collecting physical activity data and are appropriate for use in epidemiological
      studies. Because the measurement accuracy of the 24hPAR WEB was moderate to high,
      it could be suitable for evaluating the effect of interventions on individuals as
      well as for examining physical activity behavior.

PMID- 23010346
TI  - Involvement of gecko SNAP25b in spinal cord regeneration by promoting outgrowth
      and elongation of neurites.
AB  - SNARE complex mediates cellular membrane fusion events essential for
      neurotransmitter release and synaptogenesis. SNAP25, a member of the SNARE
      proteins, plays critical roles during the development of the central nervous
      system via regulation by alternative splicing and protein kinase phosphorylation.
      To date, little information is available regarding the protein in the spinal cord
      regeneration, especially for the postnatal highly expressed isoform SNAP25b. In
      the present study, we characterized gecko SNAP25b, which shared high identity
      with those of other vertebrates. Expression of gecko SNAP25b was temporally
      upregulated in both neurons of spinal cord and forming ependymal tube following
      tail amputation, coinciding with the occurrence of regenerate re-innervation.
      Overexpression of gecko wild type SNAP25b in the SH-SY5Y and undifferentiated
      PC12 cells promoted the elongation and outgrowth of neurites, while mutant
      constructs at Serine(187) resulted in differential effects for which S187A had a
      promoting role. Knockdown of endogenous SNAP25b affected the formation of
      neurites, which could be rescued by overexpression of SNAP25b. FM1-43 staining
      revealed that transfection of S187E mutant construct reduced the recruitment of
      vesicles. In addition, transfection of gecko SNAP25b in the astrocyte, which is
      absent from neuronal specific VAMP2, was capable of enhancing process elongation,
      indicating a potential for various alternative protein combinations. Taken
      together, our data suggest that gecko SNAP25b is involved in spinal cord
      regeneration by promoting outgrowth and elongation of neurites in a more
      extensive protein binding manner.

PMID- 23010347
TI  - Tumor-derived secretory clusterin induces epithelial-mesenchymal transition and
      facilitates hepatocellular carcinoma metastasis.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer
      mortality. Metastasis is the major concern that causes death in HCC. The goal of
      this study was to identify tumor-derived proteins in serum during HCC metastasis
      using an orthotopic xenograft tumor model and explore the role of key protein in
      HCC metastasis. Serum samples collected from HCCLM3-R metastatic HCC tumor model
      at specific stages of metastasis (1 wk, 3 wks and 6 wks) were subjected to iTRAQ
      labeling followed by 2DLC-ESI-MS/MS analysis. Twenty tumor-derived proteins were
      identified through human specific peptides. Secretory clusterin (sCLU), which was
      significantly upregulated during cancer progression and metastasis, was chosen
      for further study. The expression of sCLU was significantly higher in metastatic
      HCC cell lines and samples from metastatic HCC patients. ShRNA-mediated down
      regulation of sCLU resulted in a reduced migratory capacity in HCC cell lines, as
      well as a reduction in pulmonary metastasis in vivo. Overexpression of sCLU in
      HepG2 cell line showed increased cell migratory ability. Further study found that
      sCLU contributed to HCC migration and epithelial-mesenchymal transition (EMT) in
      vitro, and metastasis in vivo. In addition, sCLU also plays an important role in
      the regulation of TGF-beta1-smad3 signaling. These findings suggest that sCLU may
      promote HCC metastasis via the induction of EMT process and may be a candidate
      target for HCC therapy.

PMID- 23010348
TI  - Romidepsin (FK228) combined with cisplatin stimulates DNA damage-induced cell
      death in ovarian cancer.
AB  - OBJECTIVE: Romidepsin (FK228) was recently approved by the FDA for the treatment
      of cutaneous and peripheral T cell lymphoma. We have shown in vitro efficacy of
      FK228 in ovarian cancer. Here, our goal was to evaluate FK228 combined with
      cisplatin in ovarian cancer in vitro and in vivo. METHODS: Ovarian cancer cell
      lines were treated with cisplatin, FK228 or the combination of drugs.
      Colorimetric assays were used to determine cytotoxicity in vitro. Mice engrafted
      with 5*10(6) SKOV-3 ovarian cancer cells were treated with cisplatin, FK228 or
      the combination, and tumor weights and volumes were measured. We assessed
      molecular markers of proliferation (mib-1), apoptosis (cleaved PARP and cleaved
      caspase 3) and DNA damage (pH2AX, RAD51 and 53BP1). RESULTS: FK228 enhanced the
      cytotoxic effects of cisplatin in ovarian cells compared to vehicle-treated
      controls or each drug alone. The combination of FK228 and cisplatin-induced
      apoptosis and activated aberrant DNA damage responses demonstrated by increased
      expression of pH2AX, RAD51 and 53BP1. Mice treated with FK228, cisplatin and both
      drugs showed reduced tumor weights and volumes. Drug-treated tumors showed
      decreased mib-1 and increased cleaved-caspase 3 expression levels. The number and
      intensity of pH2AX stained cells was greatest in tumors exposed to the
      combination of FK228 and cisplatin. CONCLUSION: FK228 causes DNA damage-induced
      apoptosis and enhances the anti-tumor effects of cisplatin. The DNA damage mark
      pH2AX is activated by FK228 and cisplatin and may be a useful pharmacodynamic
      mark of these effects.

PMID- 23010349
TI  - Thickened skull, scoliosis and other skeletal findings in Unverricht-Lundborg
      disease link cystatin B function to bone metabolism.
AB  - PURPOSE: Unverricht-Lundborg disease (EPM1) is a rare type of inherited
      progressive myoclonic epilepsy resulting from mutations in the cystatin B gene,
      CSTB, which encodes a cysteine cathepsin inhibitor. Cystatin B, cathepsin K, and
      altered osteoclast bone resorption activity are interconnected in vitro. This
      study evaluated the skeletal characteristics of patients with EPM1. METHODS:
      Sixty-six genetically verified EPM1 patients and 50 healthy controls underwent
      head MRI. Skull dimensions and regional calvarial thickness was measured
      perpendicular to each calvarial bone from T1-weighted 3-dimensional images using
      multiple planar reconstruction tools. All clinical X-ray files of EPM1 patients
      were collected and reviewed by an experienced radiologist. A total of 337 X-ray
      studies were analyzed, and non-traumatic structural anomalies, dysplasias and
      deformities were registered. RESULTS: EPM1 patients exhibited significant
      thickening in all measured cranial bones compared to healthy controls. The mean
      skull thickness was 10.0+/-2.0mm in EPM1 patients and 7.6+/-1.2mm in healthy
      controls (p<0.001). The difference was evident in all age groups and was not
      explained by former phenytoin use. Observed abnormalities in other skeletal
      structures in EPM1 patients included thoracic scoliosis (35% of EPM1 patients)
      and lumbar spine scoliosis (35%), large paranasal sinuses (27%), accessory
      ossicles of the foot, and arachnodactyly (18%). CONCLUSIONS: Skull thickening and
      an increased prevalence of abnormal findings in skeletal radiographs of patients
      with EPM1 suggest that this condition is connected to defective cystatin B
      function. These findings further emphasize the role of cystatin B in bone
      metabolism in humans.

PMID- 23010350
TI  - Lack of association between CTLA-4 +49A/G and -318C/T polymorphisms and Behcet's
      disease risk: a meta-analysis.
AB  - OBJECTIVES: To more precisely determine whether there is a significant
      association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene
      polymorphisms with the susceptibility for Behcet's disease. METHODS: Eight
      studies that included data from 7 articles were identified using PubMed, Embase,
      Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge
      Infrastructure (CNKI) published before March 2012. Meta-analysis was performed
      for two CTLA-4 gene polymorphisms, +49A/G (rs231775) and -318C/T (rs5742909).
      Statistical analyses were performed using software Review Manager (version 5.1)
      and Stata (version 11.0). The pooled odds ratio (OR) with 95% confidence interval
      (95%CI) were presented. RESULTS: Overall, no significant association was detected
      in all genetic models when all studies were pooled into the meta-analysis (for
      +49A/G polymorphism: A vs. G, OR=1.173, 95% CI=0.790-1.743; A/A vs. A/G+G/G,
      OR=1.422, 95% CI=0.718-2.814; A/A+A/G vs. G/G, OR=1.421, 95% CI=0.729-2.767; and
      for -318C/T polymorphism: C vs. T, OR=1.051, 95% CI=0.844-1.307; C/C vs. T/T+C/T,
      OR=1.154 95% CI=0.891-1.495, C/C+C/T vs. T/T, OR=1.044, 95% CI=0.301-3.617).
      Furthermore, in the subgroup analysis by ethnicity, there was also lack of
      evidence for the association in Turkish patients. CONCLUSIONS: Our study failed
      to provide evidence for the genetic association between CTLA-4 +49A/G and -318C/T
      polymorphisms with Behcet's disease based on currently available evidence from
      literature. Further confirmations in large and well-designed studies including
      other CTLA-4 gene polymorphisms are needed.

PMID- 23010351
TI  - Laboratory surveillance of invasive pneumococcal disease in New South Wales,
      Australia, before and after introduction of 7-valent conjugate vaccine: reduced
      disease, but not antibiotic resistance rates.
AB  - We compared serotype distributions of Streptococcus pneumoniae isolates from
      patients aged <5 and o5 years with invasive pneumococcal disease in New South
      Wales, Australia, and antibiotic susceptibilities of isolates from the <5 years
      age group only, before (2002-2004) and after(2005-2009) introduction of the 7
      valent pneumococcal conjugate vaccine (PCV7). Overall, there were significant
      decreases in the mean annual number of referred isolates (770 vs. 515) and the
      proportion belonging to PCV7 serotypes (74% vs. 38%), but non-PCV7 serotypes,
      particularly 19A, increased (5% vs. 18%). All changes were more marked in the <5
      years age group.Susceptibility testing of isolates from the <5 years age group
      showed variation in resistance between serotypes, but significant overall
      increases in penicillin non-susceptibility (23% vs. 31%),ceftriaxone resistance
      (2% vs. 12%) and multidrug resistance (4% vs. 7%) rates ; erythromycin resistance
      fell (32% vs. 25%). Continued surveillance is needed to monitor changes following
      the introduction of 13-valent PCV in 2012.

PMID- 23010356
TI  - It's all about location, location, location: children's memory for the "where" of
      personally experienced events.
AB  - Episodic memory is defined as the ability to recall specific past events located
      in a particular time and place. Over the preschool and into the school years,
      there are clear developmental changes in memory for when events took place. In
      contrast, little is known about developmental changes in memory for where events
      were experienced. In the current research, we tested 4-, 6-, and 8-year-old
      children's memories for specific laboratory events, each of which was experienced
      in a unique location. We also tested the children's memories for the conjunction
      of the events and their locations. Age-related differences were observed in all
      three types of memory (event, location, and conjunction of event and location),
      with the most pronounced differences being in memory for conjunctions of events
      and their locations. The results have implications for our understanding of the
      development of episodic memory, including suggestions of protracted development
      of the ability to contextualize events in their spatial locations.

PMID- 23010357
TI  - Association between sequence variations of the Mediterranean fever gene and
      fibromyalgia syndrome in a cohort of Turkish patients.
AB  - OBJECTIVE: Fibromyalgia syndrome (FMS) is a common chronic widespread pain
      syndrome mainly affecting women. Genetic risk factors are known to contribute to
      the etiology of the syndrome. Clinical features show that FMS and familial
      Mediterranean fever (FMF) have some overlapping symptoms. Mediterranean fever
      (MEFV) gene has already been identified as being responsible for FMF. The aim of
      this study was to explore the frequency and clinical significance of missense
      mutations and a common polymorphism of MEFV gene in a cohort of Turkish patients
      with FMS. METHODS: The study included 187 patients with FMS and 190 healthy
      controls. Genomic DNA was isolated and genotyped using polymerase chain reaction
      (PCR) and restriction fragment length polymorphism (RFLP) analyses for the five
      MEFV gene mutations (M694V, M680I, V726A, E148Q and P369S) and one polymorphism
      (R202Q). RESULTS: There were statistically significant differences of the MEFV
      gene mutation carrier rates and allele frequencies between FMS patients and
      healthy controls (p=0.002, OR: 2.3, 95% CI: 1.35-4.16 and p=0.003, OR: 2.2, 95%
      CI: 1.28-3.75, respectively). There was also a significant difference between
      MEFV mutation carriers and non-carriers with respect to the clinical
      characteristic of morning fatigue (p=0.045). The genotype and allele frequencies
      of R202Q polymorphism of MEFV gene showed statistically significant differences
      between FMS patients and healthy controls (p<0.0001 and p<0.0001, respectively)
      and especially the homozygous AA genotype was significantly higher in FMS
      patients than in healthy controls (p=0.0003; OR: 7.43, 95% CI: 2.14-39.75). While
      13 of the 44 FMS patients with MEFV mutation had R202Q polymorphism, none of the
      22 controls with MEFV mutation had R202Q polymorphism. Stratification analysis
      according to clinical features for this disease reveals that morning fatigue and
      irritable bowel syndrome had associations with R202Q polymorphism (p=0.022 and
      p=0.031 respectively). CONCLUSION: The results of this study suggest that MEFV
      gene mutations and polymorphism are positively associated with predisposition to
      develop FMS. Further studies with larger populations will be required to confirm
      these findings.

PMID- 23010358
TI  - Effects of hemoglobin D and E on the measurement of HbA1c with the modified
      Menarini/ARKRAY ADAMS A1c HA-8180V analyser.

PMID- 23010359
TI  - Functional matrix metalloproteinase (MMP)-9 genetic variants modify the effects
      of hemodialysis on circulating MMP-9 levels.
AB  - BACKGROUND: Altered levels of matrix metalloproteinases (MMPs) and their
      inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in
      cardiovascular alterations associated with end stage kidney disease (ESKD).
      Genetic polymorphisms in MMP-9 gene affect MMP-9 levels. We examined how MMP-9
      polymorphisms and haplotypes affect the changes in plasma MMP-9 and TIMP-1 levels
      found in patients with ESKD undergoing hemodialysis. METHODS: We studied 94 ESKD
      patients undergoing hemodialysis for at least 3 months. MMP-9 and TIMP-1 were
      measured by ELISA in plasma from blood samples collected before and after a
      session of hemodialysis. Genotypes for three MMP-9 polymorphisms (C(-1562)T,
      rs3918242; -90 (CA)(14-24), rs2234681; and Q279R, rs17576) were determined by
      Taqman(r) Allele Discrimination Assay and real-time polymerase chain reaction.
      Haplotype frequencies were determined with the software program PHASE 2.1.
      RESULTS: Hemodialysis increased MMP-9 and TIMP-1 levels (P<0.05). Genotypes had
      no effects on baseline MMP-9 and TIMP-1 levels (P>0.05). Hemodialysis increased
      MMP-9 and TIMP-1 levels in subjects with the CC (but not CT or TT) genotype for
      the C(-1562)T polymorphism (P<0.05), and increased MMP-9 levels in subjects with
      the QQ (but not QR or RR) genotype for the Q279R polymorphism (P<0.05), whereas
      the CA(n)(14-24) polymorphism had no major effects. While MMP-9 haplotypes had no
      effects on baseline MMP-9 levels (P>0.05), hemodialysis increased MMP-9 levels
      and MMP-9/TIMP-1 ratios in subjects carrying the CLQ haplotype (P=0.0012 and
      P=0.0045, respectively). CONCLUSION: ESKD patients with the QQ genotype for the
      Q279R polymorphism or with the CLQ haplotype are exposed to more severe increases
      in MMP-9 levels after hemodialysis. Such patients may benefit from the use of MMP
      inhibitors.

PMID- 23010360
TI  - A novel, potent, and selective inhibitor of cardiac late sodium current
      suppresses experimental arrhythmias.
AB  - Inhibition of cardiac late sodium current (late I(Na)) is a strategy to suppress
      arrhythmias and sodium-dependent calcium overload associated with myocardial
      ischemia and heart failure. Current inhibitors of late I(Na) are unselective and
      can be proarrhythmic. This study introduces GS967 (6-[4-(trifluoromethoxy)phenyl]
      3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine), a potent and selective
      inhibitor of late I(Na), and demonstrates its effectiveness to suppress
      ventricular arrhythmias. The effects of GS967 on rabbit ventricular myocyte ion
      channel currents and action potentials were determined. Anti-arrhythmic actions
      of GS967 were characterized in ex vivo and in vivo rabbit models of reduced
      repolarization reserve and ischemia. GS967 inhibited Anemonia sulcata toxin II
      (ATX-II)-induced late I(Na) in ventricular myocytes and isolated hearts with
      IC(50) values of 0.13 and 0.21 uM, respectively. Reduction of peak I(Na) by GS967
      was minimal at a holding potential of -120 mV but increased at -80 mV. GS967 did
      not prolong action potential duration or the QRS interval. GS967 prevented and
      reversed proarrhythmic effects (afterdepolarizations and torsades de pointes) of
      the late I(Na) enhancer ATX-II and the I(Kr) inhibitor E-4031 in isolated
      ventricular myocytes and hearts. GS967 significantly attenuated the proarrhythmic
      effects of methoxamine+clofilium and suppressed ischemia-induced arrhythmias.
      GS967 was more potent and effective to reduce late I(Na) and arrhythmias than
      either flecainide or ranolazine. Results of all studies and assays of binding and
      activity of GS967 at numerous receptors, transporters, and enzymes indicated that
      GS967 selectively inhibited late I(Na). In summary, GS967 selectively suppressed
      late I(Na) and prevented and/or reduced the incidence of experimentally induced
      arrhythmias in rabbit myocytes and hearts.

PMID- 23010361
TI  - A TRPC3 blocker, ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5
      (trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), prevents stent-induced
      arterial remodeling.
AB  - TRPC-mediated Ca(2+) entry has been implicated in the control of smooth muscle
      proliferation and might represent a pivotal mechanism underlying in-stent
      restenosis. As we have observed significant expression of TRPC3 in human smooth
      muscle from the coronary artery as well as the aorta, we tested the efficiency of
      a recently discovered TRPC3 selective Ca(2+) entry blocker Pyr3 to prevent
      vascular smooth muscle proliferation and stent implantation-induced hyperplasia
      of human aorta. The effect of Pyr3 on proliferation was measured by detection of
      BrdU incorporation and PCNA expression in human coronary smooth muscle and
      microvascular endothelium, which displays significantly smaller expression levels
      of TRPC3 as compared with smooth muscle. Pyr3 inhibited smooth muscle
      proliferation but lacked detectable effects on endothelial proliferation.
      Measurements of ATP-induced Ca(2+) signals revealed that Pyr3 suppressed agonist
      induced Ca(2+) entry more effectively in vascular smooth muscle than in
      endothelial cells. Inhibitory effects of Pyr3 on stent implantation-induced
      arterial injury was tested using a novel in vitro model of in-stent hyperplasia
      in human arteries based on organ typical culture of human aortic constructs. Pyr3
      effectively prevented increases in tissue levels of PCNA and Ki-67 at 2 weeks
      after stent implantation into human aortae. Similarly, proliferation markers were
      significantly suppressed when implanting a Pyr3-releasing stent prototype as
      compared with a bare metal stent (BMS) control. Our results suggest TRPC3 as a
      potential target for pharmacological control of smooth muscle proliferation.
      Selectively inhibition of TRPC Ca(2+) entry channels in vascular smooth muscle is
      suggested as a promising strategy for in-stent restenosis prevention.

PMID- 23010362
TI  - Functional and structural interaction of (-)-reboxetine with the human
      alpha4beta2 nicotinic acetylcholine receptor.
AB  - The interaction of the selective norepinephrine reuptake inhibitor (-)-reboxetine
      with the human alpha4beta2 nicotinic acetylcholine receptor (nAChR) in different
      conformational states was studied by several functional and structural
      approaches. Patch-clamp and Ca(2+)-influx results indicate that (-)-reboxetine
      does not activate halpha4beta2 nAChRs via interaction with the orthosteric sites,
      but inhibits agonist-induced halpha4beta2 activation by a noncompetitive
      mechanism. Consistently, the results from the electrophysiology-based functional
      approach suggest that (-)-reboxetine may act via open channel block; therefore,
      it is capable of producing a use-dependent type of inhibition of the halpha4beta2
      nAChR function. We tested whether (-)-reboxetine binds to the luminal
      [(3)H]imipramine site. The results indicate that, although (-)-reboxetine binds
      with low affinity to this site, it discriminates between the resting and
      desensitized halpha4beta2 nAChR ion channels. Patch-clamp results also indicate
      that (-)-reboxetine progressively inhibits the halpha4beta2 nAChR with two-fold
      higher potency at the end of one-second application of agonist, compared with the
      peak current. The molecular docking studies show that (-)-reboxetine blocks the
      ion channel at the level of the imipramine locus, between M2 rings 6' and 14'. In
      addition, we found a (-)-reboxetine conformer that docks in the helix bundle of
      the alpha4 subunit, near the middle region. According to molecular dynamics
      simulations, (-)-reboxetine binding is stable for both sites, albeit less stable
      than imipramine. The interaction of these drugs with the helix bundle might alter
      allostericaly the functionality of the channel. In conclusion, the clinical
      action of (-)-reboxetine may be produced (at least partially) by its inhibitory
      action on halpha4beta2 nAChRs.

PMID- 23010363
TI  - Proteins with an alpha/beta hydrolase fold: Relationships between subfamilies in
      an ever-growing superfamily.
AB  - Alpha/beta hydrolases function as hydrolases, lyases, transferases, hormone
      precursors or transporters, chaperones or routers of other proteins. The amount
      of structural and functional available data related to this protein superfamily
      expands exponentially, as does the number of proteins classified as alpha/beta
      hydrolases despite poor sequence similarity and lack of experimental data.
      However the superfamily can be rationally divided according to sequence or
      structural homologies, leading to subfamilies of proteins with potentially
      similar functions. Since the discovery of proteins homologous to cholinesterases
      but devoid of enzymatic activity (e.g., the neuroligins), divergent functions
      have been ascribed to members of other subfamilies (e.g., lipases,
      dipeptidylaminopeptidase IV, etc.). To study the potentially moonlighting
      properties of alpha/beta hydrolases, the ESTHER database (for ESTerase and
      alpha/beta Hydrolase Enzymes and Relatives; http://bioweb.ensam.inra.fr/esther),
      which collects, organizes and disseminates structural and functional information
      related to alpha/beta hydrolases, has been updated with new tools and the web
      server interface has been upgraded. A new Overall Table along with a new Tree
      based on HMM models has been included to tentatively group subfamilies. These
      tools provide starting points for phylogenetic studies aimed at pinpointing the
      origin of duplications leading to paralogous genes (e.g., acetylcholinesterase
      versus butyrylcholinesterase, or neuroligin versus carboxylesterase). Another of
      our goals is to implement new tools to distinguish catalytically active enzymes
      from non-catalytic proteins in poorly studied or annotated subfamilies.

PMID- 23010364
TI  - DNA barcoding of the Mexican sedative and anxiolytic plant Galphimia glauca.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Galphimia glauca (Malpighiaceae) is a Mexican plant
      popularly used as a tranquilizer in the treatment of nervous system disorders,
      although it is also used to treat other common illnesses. AIM OF THE STUDY: The
      aim of this investigation is to find out if populations of Galphimia glauca
      collected in different regions and ecosystems in Mexico actually belong to the
      same species by using the contemporary technique of DNA barcodes. Our previous
      metabolic profiling study demonstrates that different collections of this plant
      obtained from various geographical areas exhibited diverse chemical profiles in
      terms of the active compounds named Galphimines. We expected the DNA barcodes
      apart from indicating the different species of Galphimia would indicate the
      active populations. MATERIALS AND METHODS: We employed matK, rpoC1 and rbcL DNA
      barcodes to indicate the different species. Furthermore to investigate the
      possible impact of the several different ecosystems where the seven populations
      were collected, thin layer chromatography was employed to create a partial
      chemical profile, which was then compared with the metabolic profiles obtained by
      (1)H-NMR and multivariate data analysis. RESULTS AND CONCLUSIONS: This study
      showed that the seven populations here analyzed contain at least three different
      species of the genus Galphimia, although each individual population is
      homogeneous. Interestingly our TLC analysis clearly showed that the active
      populations displayed a distinctively unique chemical profile. This work also
      showed that the use of DNA barcodes combined with chemical profile analysis is an
      excellent approach to solve the problems of quality control in the development of
      Galphimia-based medicines as well as for any breeding programs for this species.

PMID- 23010365
TI  - Anti-inflammatory and anti-nociceptive properties of Prunus padus.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Prunus padus Linne has been widely used as a
      traditional medicine, with beneficial effects in numerous diseases, including
      stroke, neuralgia and hepatitis. In this study, we demonstrated anti-inflammatory
      and anti-nociceptive activities of the methylene chloride fraction of P. padus
      (MPP). MATERIALS AND METHODS: In vitro studies, the anti-inflammatory effects of
      MPP were examined using IFN-gamma/LPS-activated murine peritoneal macrophage
      model. To confirm the anti-inflammatory effects of MPP in vivo, trypsin-induced
      paw edema test was also conducted. The anti-nociceptive activities of MPP were
      measured using various experimental pain models including thermal nociception
      methods such as the tail immersion test and the hot plate test as well as
      chemical nociception methods like acetic acid-induced writhing test and formalin
      test. To determine whether analgesic activity of MPP is connected with the opioid
      receptor, we carried out combination test with naloxone, a nonselective opioid
      receptor antagonist. RESULTS: In the current study, MPP showed potent inhibitory
      effect on IFN-gamma/LPS-induced NO production. MPP also suppressed not only iNOS
      enzyme activity but also iNOS expression. Moreover, MPP inhibited COX-2
      expression dose dependently. IFN-gamma/LPS stimulation induced the translocation
      of NF-kappaB to nucleus but it was attenuated in the presence of MPP. In vivo
      study revealed that MPP could reduce paw volume after subplantar injection of
      trypsin. In addition, MPP showed potent analgesic activities both thermal and
      chemical nociception compared to tramadol and indomethacin. Furthermore, pre
      treatment of naloxone slightly suppress the analgesic activity of MPP indicating
      that MPP acts as a partial opioid receptor agonist. CONCLUSIONS: In the present
      study, MPP showed potent anti-inflammatory properties through not only by
      suppressing various inflammatory mediators in vitro, but reducing the
      inflammatory edema in vivo. MPP also exhibited strong anti-nociceptive activities
      via both central and peripheral mechanism by acting as a partial opioid agonist.
      Based on these results we suggest that P. padus has the potential to provide a
      therapeutic approach to inflammation-mediated chronic diseases as an effective
      anti-inflammatory agent and painkiller.

PMID- 23010366
TI  - Protective effect of Danhong injection on cerebral ischemia-reperfusion injury in
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DH), a Chinese medical
      product, is used extensively for the treatment of cerebrovascular diseases such
      as acutely cerebral infarction in clinic. AIM OF THE STUDY: To explore the
      protective effect and the relevant mechanisms of DH on cerebral ischemia
      reperfusion (I/R) injury. MATERIALS AND METHODS: Cerebral I/R injury was induced
      through four-vessel occlusion (4-VO) or middle cerebral artery occlusion (MCAO).
      Adult male SD rats were randomly divided into six kinds of groups: normal control
      group, sham-operated group, I/R injury group, DH-treated groups at doses of
      0.5ml/kg, 1.0ml/kg and 2.0ml/kg. The effects of DH on murine neurological
      deficits and cerebral infarct volume, 6-keto-prostagladin F(1alpha) (6-keto
      PGF(1alpha)) level, malondialdehyde (MDA) level and superoxide dismutase (SOD)
      activity in brain tissue, as well as the activities of plasma tissue-type
      plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) after I/R
      were evaluated. Moreover, the expressions of Bcl-2 and Bax protein were detected
      by immunohistochemistry. RESULTS: There was no significant difference between the
      control group and the sham-operated group based on the measurement indicators.
      Compared with the vehicle-treated group, rats treated with DH showed dose
      dependent reductions in brain infarction size, and improvement of neurological
      outcome. The level of 6-keto-PGF(1alpha) and the activities of SOD and plasma t
      PA were enhanced significantly, whereas the level of MDA and the activity of
      plasma PAI were declined significantly. The immunohistochemical staining results
      also revealed that the expression of Bcl-2 protein was up-regulated and that of
      Bax protein was down-regulated when exposed to DH. CONCLUSION: DH demonstrates a
      strong ameliorative effect on cerebral I/R damage in rats by its anticoagulant,
      antithrombotic, antifibrinolytic and antioxidant activities. Furthermore,
      suppressing apoptosis through regulating Bcl-2 and Bax protein expressions should
      be another potential mechanism by which DH exerts its neuroprotective function.

PMID- 23010367
TI  - Breastfeeding and short sleep duration in mothers and 6-11-month-old infants.
AB  - This study examined breastfeeding and sleep in 77 dyads of mothers and infants 6
      11 months old. Data revealed no significant difference in sleep patterns between
      breastfed and non-breastfed infants. Controlling for variables including
      breastfeeding status, only infant nighttime sleep duration was significant in
      predicting maternal short sleep duration.

PMID- 23010368
TI  - Quantitative evaluation of neurosensory disturbance after bilateral sagittal
      split osteotomy using Semmes-Weinstein monofilaments: a systematic review.
AB  - PURPOSE: To evaluate neurosensory disturbance of the inferior alveolar nerve,
      after bilateral sagittal split osteotomy, from before surgery to 1 year
      postoperatively, by quantitatively evaluating published data using Semmes
      Weinstein monofilaments. MATERIALS AND METHODS: A literature search was conducted
      by use of PubMed, EMBASE, Scopus, Web of Science, CINAHL (Cumulative Index to
      Nursing and Allied Health Literature), and the Cochrane Library in June 2012. The
      related citations function in PubMed, reference lists, and authors' names were
      used to expand the search. From each included study, study and sample
      characteristics were extracted, as were results. The main outcome was the
      lightest pressure the patient could discern at 1 month and at 1 year after the
      osteotomy procedure, in comparison with before surgery. RESULTS: Of the 3,107
      articles initially identified, 7 were chosen according to the preset inclusion
      and exclusion criteria. The results from the studies could not be combined for
      the purpose of a meta-analysis because of the lack of standardization. Only 2
      studies provided data that allowed an estimation of average detectable applied
      force to be carried out. Before surgery, the lowest detectable threshold
      corresponded to a mean of 0.07 to 0.16 g. At 1 month after surgery, the lowest
      detectable threshold averaged 6 g, and at 1 year after surgery, the mean value
      was 0.16 to 0.4 g. CONCLUSIONS: After bilateral sagittal split osteotomy, at 1
      month after surgery, the sensory threshold increases approximately 35- to 85-fold
      compared with the presurgery threshold. Within 1 year, the threshold normally
      decreases almost to presurgery levels, representing 96% to 98% sensory recovery.
      Studies should aim to quantitatively use the Semmes-Weinstein monofilament method
      and standardize the presentation of results.

PMID- 23010370
TI  - Risk factors for the development of lower border defects after bilateral sagittal
      split osteotomy.
AB  - PURPOSE: Defects at the lower border of the mandible may persist after bilateral
      sagittal split osteotomy (BSSO). The purpose of this study was to estimate the
      frequency of lower border defects after BSSO and to identify factors associated
      with the development of these defects. MATERIALS AND METHODS: This retrospective
      study included patients who underwent BSSO at St John's Hospital from January
      2010 through December 2011. The predictor variables were length of advancement
      and inclusion of the full thickness of the lower border in the split. The outcome
      variable was the presence or absence of a lower border defect. Other variables
      were age and the side of the mouth. All analyses were performed using SAS 9.22.
      RESULTS: The analysis included 400 operation sites in 200 patients (124 female,
      76 male; median age, 24.5 yr; range, 14 to 57 yr). A defect at the mandibular
      border presented in more than one third of operation sites. Inclusion of the full
      thickness of the lower border in the split, length of advancement, side of the
      jaw, and age (P < .0001) were risk factors for a permanent defect at the lower
      border of the osteotomy gap after BSSO. CONCLUSIONS: Inclusion of the full
      thickness of the lower mandibular border, the age of the patient, and the
      magnitude of advancement during BSSO are important predictors of whether a
      postoperative mandibular defect will remain after surgery. Surgeons should ensure
      that the lingual cortex of the lower border is not included in the split in large
      mandibular advancements.

PMID- 23010369
TI  - Dental implant stability is influenced by implant diameter and localization and
      by the use of plasma rich in growth factors.
AB  - PURPOSE: The objective was to analyze the factors that influence the stability of
      dental implants at 12 weeks after implant placement as measured by resonance
      frequency analysis using the Osstell system. MATERIALS AND METHODS: This
      prospective clinical study was performed in 235 implants placed in 93 patients at
      the Oral Surgery and Implantology Clinic of the University of Granada. The
      gathered predictor variables were grouped into patient variables, implant
      variables, operative variables, and baseline implant stability quotient (ISQ).
      All variables were analyzed in a multivariate model to determine their influence
      on the ISQ score at 12 weeks after implant insertion (outcome variable). SUDAAN
      software was used for clustered sampling (multiple implants in patients).
      RESULTS: Two hundred thirty-five dental implants were placed in 47 men (50.5%)
      and 46 women (49.5%; total, 93 patients; mean age, 52.13 +/- 11.23 years; range,
      27 to 76 years). No association was found between the patient variables and the
      ISQ values at 12 weeks. Among implant variables, worse ISQ values at 12 weeks
      were observed for a narrow diameter (P < .001) and maxillary implants (P = .006).
      Among surgical technique variables, the use of plasma rich in growth factors (P =
      .011) showed the best ISQ values at 12 weeks. CONCLUSIONS: The diameter and
      localization of implants and the application of plasma rich in growth factors
      influenced the stability of implants measured at 12 weeks of wound healing.
      Accordingly, stability was less with a narrower implant diameter and maxillary
      localization and greater with implants humidified with plasma rich in growth
      factors.

PMID- 23010371
TI  - Rapid, early-onset group a streptococcus infection after impacted third molar
      removal: a review and case series.

PMID- 23010372
TI  - Maxillary yaw as the primary predictor of maxillary dental midline deviation: 3D
      analysis using cone-beam computed tomography.
AB  - PURPOSE: The purpose of this study was to investigate which factors affect upper
      dental midline deviation in dentofacial deformity patients using cone-beam
      computed tomography analysis. PATIENTS AND METHODS: Twenty-eight patients were
      selected for this study. Subjects were divided into 2 groups according to the
      amount of upper incisor (U1) midline deviation from the clinical facial midline:
      group 1 (U1 deviation <2 mm) and group 2 (U1 deviation >2 mm). Linear
      measurements, angles, and reference planes on 3-dimensional (3D) computed
      tomograms were obtained. The predictor variables were maxillary yaw, palatal
      plane angle, differences of maxillary point to the coronal and sagittal planes,
      and maxillary canting. The outcome variable was U1 deviation. The variables
      between the 2 groups and 2 sides were analyzed with a t test. Pearson correlation
      coefficient and multiple regression analysis were also calculated within each
      group for each measurement against the U1 deviation to determine which variables
      affect U1 deviation. P < .05 was considered statistically significant. RESULTS:
      The patients were evenly distributed between each group (n = 14 in each group).
      There was significant deviation of U1 from the sagittal plane in group 2 compared
      with group 1 (0.99 mm in group 1 vs 1.73 mm in group 2, P < .05). When we
      compared yaw with the sagittal plane, group 2 was more rotated than group 1 (1.16
      degrees  in group 1 vs 2.28 degrees  in group 2, P < .01). Through multiple
      regression analysis, the primary predictor variable for U1 deviation was
      maxillary yaw (P < .05). CONCLUSIONS: This study suggests that maxillary yaw is
      the primary contributing factor for upper dental midline deviation. The use of
      maxillary yaw should be considered when one is performing orthognathic surgery in
      patients with U1 deviation to achieve optimum esthetics.

PMID- 23010373
TI  - Oral tori are associated with local mechanical and systemic factors: a case
      control study.
AB  - PURPOSE: To estimate if various dental factors, medications, and medical
      conditions are associated with an increased risk for the presence of oral tori.
      MATERIALS AND METHODS: Using a case-control study design, the investigators
      identified and adjudicated a sample of cases with torus palatinus (TP) and/or
      torus mandibularis (TM) during a 1.5-year period. The medical records were
      abstracted and data on dental factors, temporomandibular dysfunction (TMD),
      medications, and medical conditions were recorded. Risk estimates were calculated
      as adjusted odds ratios (AORs) with 95% confidence intervals (CIs) using
      conditional logistic regression analyses, and the P value was set at .05.
      RESULTS: The sample was composed of 66 subjects with TM, 34 subjects with TP, and
      100 control subjects from the same database. Any form of oral torus (TP and/or
      TM) was associated significantly with TMD (AOR, 10.51; 95% CI, 4.46 to 24.78;
      P<.01) and tooth attrition (AOR, 5.22; 95% CI, 2.32 to 11.77; P<.01). TP was
      associated significantly with TMD (AOR, 4.14; 95% CI, 1.21 to 14.21; P<.05),
      tooth attrition (AOR, 38.18; 95% CI, 7.20 to 202.41; P<.01), and treated
      hypertension (AOR, 6.64; 95% CI, 1.31 to 33.57; P<.05). TM was associated
      significantly with TMD (AOR, 5.77; 95% CI, 2.38 to 13.98; P<.01), tooth attrition
      (AOR, 6.69; 95% CI, 2.78 to 16.14; P<.01), and a penicillin allergy (AOR, 4.45;
      95% CI, 1.05 to 18.83; P<.05). CONCLUSIONS: This study provides clinical evidence
      showing significant associations between oral tori and various dental factors,
      medications, and medical conditions. These findings add to the list of
      environmental factors believed to contribute to the formation of oral tori.

PMID- 23010374
TI  - Management of ranula: 9 years' clinical experience in pediatric and adult
      patients.
AB  - PURPOSE: The aim of the present study was to evaluate the long-term results in
      the authors' department in the management of patients with oral and plunging
      ranulas. A specific diagnostic and therapeutic approach is suggested based on
      these data and data from the literature. MATERIALS AND METHODS: A retrospective
      analysis of 65 patients with a final diagnosis of ranula was carried out. The
      medical records were evaluated for the principal demographic, clinical,
      diagnostic, and therapeutic data. Statistical analysis was used to compare
      outcomes of the different treatments. RESULTS: Treatments that included complete
      sublingual gland excision were associated with the lowest recurrence rate (3.6%),
      followed by partial sublingual gland excision (9.1%), marsupialization (13%), and
      ranula excision (36.7%). Nine patients (13.8%) had recurrences. A statistically
      significant difference was observed (P = .01) in the recurrence rate between
      complete sublingual gland excision and ranula excision alone. Complications
      developed in 7 patients (10.8%). Ultrasonography performed in all patients showed
      an intimate relation among the cyst, mylohyoid muscle, and sublingual gland.
      Dehiscence of the mylohyoid muscle was noted in some cases. CONCLUSIONS: The
      surgical experience in the authors' department confirms the different treatments
      that are offered for ranula. Sublingual gland excision should be the preferred
      treatment, but marsupialization may be useful as an alternative minimally
      invasive procedure, with a success rate higher than 85% and no risk of increased
      complications if revision surgery is needed. Ultrasound is the recommended
      diagnostic tool, in addition to the clinical examination, for the differential
      diagnosis and during follow-up.

PMID- 23010375
TI  - Predicting third molar surgery operative time: a validated model.
AB  - PURPOSE: The purpose of the present study was to develop and validate a
      statistical model to predict third molar (M3) operative time. MATERIALS AND
      METHODS: This was a prospective cohort study consisting of a sample of subjects
      presenting for M3 removal. The demographic, anatomic, and operative variables
      were recorded for each subject. Using an index sample of randomly selected
      subjects, a multiple linear regression model was generated to predict the
      operating time. A nonoverlapping group of randomly selected subjects (validation
      sample) was used to assess model accuracy. P<=.05 was considered significant.
      RESULTS: The sample was composed of 150 subjects (n) who had 450 (k) M3s removed.
      The index sample (n=100 subjects, k=313 M3s extracted) had a mean age of 25.4+/
      10.0 years. The mean extraction time was 6.4+/-7.0 minutes. The multiple linear
      regression model included M3 location, Winter's classification, tooth morphology,
      number of teeth extracted, procedure type, and surgical experience (R2=0.58). No
      statistically significant differences were seen between the index sample and the
      validation sample (n=50, k=137) for any of the study variables. Compared with the
      index model, the beta-coefficients of the validation model were similar in
      direction and magnitude for most variables. Compared with the observed extraction
      time for all teeth in the sample, the predicted extraction time was not
      significantly different (P=.16). CONCLUSIONS: Fair agreement was seen between the
      beta-coefficients for our multiple models in the index and validation
      populations, with no significant difference in the predicted and observed
      operating times.

PMID- 23010376
TI  - Prefabricated iliac crest transplant.
AB  - PURPOSE: Our aim was to augment the extremely atrophic mandibular alveolar crest
      with a pedicled transplant as the best option for a satisfactory preprosthetic
      outcome. MATERIALS AND METHODS: After computed tomography of the mandible, a
      model was milled for 6 patients. The iliac crest transplant with its vascular
      pedicle was harvested and, after preliminary preparation, fixed to the model. The
      transplant was then placed in the axilla. After 3 months, the graft was removed
      and fixed to the mandible. RESULTS: The prefabricated transplant fit exactly in
      all 6 patients. The length of the pedicle and coverage with the newly developed
      alveolar mucous membrane were satisfactory. The grafts allowed prosthetic
      reconstruction with good functional outcomes. No bone loss was observed during 7
      years of follow-up. Additionally, indocyanine green angiography showed good
      perfusion in 4 patients after 6 months. CONCLUSIONS: The results suggest that
      carefully prefabricated pedicled transplants can augment an atrophied mandibular
      alveolar crest.

PMID- 23010377
TI  - Does provider-initiated counselling and testing (PITC) strengthen early diagnosis
      and treatment initiation? Results from an analysis of an urban cohort of HIV
      positive patients in Lusaka, Zambia.
AB  - INTRODUCTION: Building on earlier works demonstrating the effectiveness and
      acceptability of provider-initiated counselling and testing (PITC) services in
      integrated outpatient departments of urban primary healthcare clinics (PHCs),
      this study seeks to understand the relative utility of PITC services for
      identifying clients with early-stage HIV-related disease compared to traditional
      voluntary testing and counselling (VCT) services. We additionally seek to
      determine whether there are any significant differences in the clinical and
      demographic profile of PITC and VCT clients. METHODS: Routinely collected, de
      identified data were collated from two cohorts of HIV-positive patients referred
      for HIV treatment, either from PITC or VCT in seven urban-integrated PHCs.
      Univariate and multivariate analyses were conducted to compare the two cohorts
      across demographic and clinical characteristics at enrolment. RESULTS: Forty-five
      per cent of clients diagnosed via PITC had CD4 < 200, and more than 70% (i.e. two
      thirds) had CD4 < 350 at enrollment, with significantly lower CD4 counts than
      that of VCT clients (p < 0.001). PITC clients were more likely to be male (p =
      0.0005) and less likely to have secondary or tertiary education (p < 0.0001).
      Among those who were initiated on antiretroviral therapy (ART), PITC clients had
      lower odds of initiating treatment within four weeks of enrollment into HIV care
      (adjusted odds ratio, or AOR: 0.86; 95% confidence interval, or CI: 0.75-0.99; p
      = 0.035) and significantly lower odds of retention in care at six months (AOR:
      0.84; CI: 0.77-0.99; p = 0.004). CONCLUSIONS: In Lusaka, Zambia, large numbers of
      individuals with late-stage HIV are being incidentally diagnosed in outpatient
      settings. Our findings suggest that PITC in this setting does not facilitate more
      timely diagnosis and referral to care but rather act as a "safety net" for
      individuals who are unwilling or unable to seek testing independently. Further
      work is needed to document the way provision of clinic-based services can be
      strengthened and linked to community-based interventions and to address socio
      cultural norms and socio-economic status that underpin healthcare-seeking
      behaviour.

PMID- 23010378
TI  - Patients' demographic and clinical characteristics and level of care associated
      with lost to follow-up and mortality in adult patients on first-line ART in
      Nigerian hospitals.
AB  - INTRODUCTION: Clinical outcome is an important determinant of programme success.
      This study aims to evaluate patients' baseline characteristics as well as level
      of care associated with lost to follow-up (LTFU) and mortality of patients on
      antiretroviral treatment (ART). METHODS: Retrospective cohort study using routine
      service data of adult patients initiated on ART in 2007 in 10 selected hospitals
      in Nigeria. We captured data using an electronic medical record system and
      analyzed using Stata. Outcome measures were probability of being alive and
      retained in care at 12, 24 and 36 months on ART. Potential predictors associated
      with time to mortality and time to LTFU were assessed using competing risks
      regression models. RESULTS: After 12 months on therapy, 85% of patients were
      alive and on ART. Survival decreased to 81.2% and 76.1% at 24 and 36 months,
      respectively. Median CD4 count for patients at ART start, 12, 18 and 24 months
      were 152 (interquartile range, IQR: 75 to 242), 312 (IQR: 194 to 450), 344 (IQR:
      227 to 501) and 372 (IQR: 246 to 517) cells/ul, respectively. Competing risk
      regression showed that patients' baseline characteristics significantly
      associated with LTFU were male (adjusted sub-hazard ratio, sHR = 1.24 [95% CI:
      1.08 to 1.42]), ambulatory functional status (adjusted sHR = 1.25 [95% CI: 1.01
      to 1.54]), World Health Organization (WHO) clinical Stage II (adjusted sHR = 1.31
      [95% CI: 1.08 to 1.59]) and care in a secondary site (adjusted sHR = 0.76 [95%
      CI: 0.66 to 0.87]). Those associated with mortality include CD4 count < 50
      cells/ul (adjusted sHR = 2.84 [95% CI: 1.20 to 6.71]), WHO clinical Stage III
      (adjusted sHR = 2.67 [95% CI: 1.26 to 5.65]) and Stage IV (adjusted sHR = 5.04
      [95% CI: 1.93 to 13.16]) and care in a secondary site (adjusted sHR = 2.21 [95%
      CI: 1.30 to 3.77]). CONCLUSIONS: Mortality was associated with advanced HIV
      disease and care in secondary facilities. Earlier initiation of therapy and
      strengthening systems in secondary level facilities may improve retention and
      ultimately contribute to better clinical outcomes.

PMID- 23010379
TI  - Preferred antiretroviral drugs for the next decade of scale up.
AB  - Global commitments aim to provide antiretroviral therapy (ART) to 15 million
      people living with HIV by 2015, and recent studies have demonstrated the
      potential for widespread ART to prevent HIV transmission. Increasingly, countries
      are adapting their national guidelines to start ART earlier, for both clinical
      and preventive benefits. To maximize the benefits of ART in resource-limited
      settings, six key principles need to guide ART choice: simplicity, tolerability
      and safety, durability, universal applicability, affordability and heat
      stability. Currently available drugs, combined with those in late-stage clinical
      development, hold great promise to simplify treatment in the short term. Over the
      longer-term, newer technologies, such as long-acting formulations and
      nanotechnology, could radically alter the treatment paradigm. This commentary
      reviews recommendations made in an expert consultation on treatment scale up in
      resource-limited settings.

PMID- 23010380
TI  - Utility of spine bone mineral density in fracture prediction within FRAX.
AB  - Predicting individuals at risk for fracturing and modifying that risk are
      important in preventative health. Our aim was to quantify the impact of spine
      bone mineral density (BMD) on fracture risk prediction and determine the positive
      predictive value of fracture prediction using the lowest BMD value at the femoral
      neck, total hip, or lumbar spine. A retrospective cross-sectional analysis of
      15,033 women was performed, assessing the contribution of age, body mass index,
      number of clinical risk factors, T-score, and osteoporosis category to the
      presence of fracture. In patients whose lumbar spine T-scores are 1 or 2
      osteoporosis categories lower than femoral neck, there is an approximately 30%
      increased risk of fracture compared with the femoral neck alone. For patients
      younger than 60 years, the odds ratio of having a fracture based on the presence
      of lumbar spine osteoporosis was greater than that based on femoral neck
      osteoporosis. Osteoporosis at the total hip correlated best with the presence of
      fracture. When using FRAX, we recommend that the 10-yr fracture prediction be
      adjusted when lumbar spine T-score is 1-2 osteoporosis categories lower than the
      femoral neck T-score or when lumbar spine T-score is >=1 standard deviation less
      than femoral neck T-score.

PMID- 23010381
TI  - The role of the NMDA receptors and l-arginine-nitric oxide-cyclic guanosine
      monophosphate pathway in the antidepressant-like effect of duloxetine in the
      forced swimming test.
AB  - Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor used as
      antidepressant. However, its mechanisms of action are not fully understood. This
      study investigated the effect of duloxetine in the mouse forced swimming test
      (FST) and in the tail suspension test (TST) and the involvement of the NMDA
      receptors and the l-arginine-NO-cGMP pathway in its effect in the FST. Duloxetine
      reduced the immobility time both in the FST and in the TST (dose range of 1
      30mg/kg, i.p.), without changing locomotion in an open-field. Duloxetine
      administered orally (1-30mg/kg) also reduced the immobility time in the FST. The
      effect of duloxetine (10mg/kg, p.o.) in the FST was prevented by pre-treatment
      with NMDA (0.1pmol/site, i.c.v.), d-serine (30MUg/site, i.c.v.), (l-arginine
      (750mg/kg, i.p.), S-nitroso-N-acetyl-penicillamine (SNAP, 25MUg/site, i.c.v) or
      sildenafil (5mg/kg, i.p.). The administration of MK-801 (0.001mg/kg, i.p.), 7
      nitroindazole (50mg/kg, i.p.), methylene blue (20mg/kg, i.p.) or 1H
      [1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30pmol/site i.c.v.) in
      combination with a sub-effective dose of duloxetine (0.3mg/kg, p.o.) reduced the
      immobility time in the FST. Moreover, the administration of duloxetine (10mg/kg)
      produced a reduction in NOx levels in the hippocampus and cerebral cortex.
      Altogether the results suggest that the effect of duloxetine in the FST is
      dependent on either a blockade of NMDA receptors or an inhibition of NO. In
      addition, our results further reinforce the role of NMDA receptors and l-arginine
      NO-cGMP pathway, besides the monoaminergic systems, in the mechanism of action of
      current prescribed antidepressant agents.

PMID- 23010382
TI  - Lithium and valproate modulate energy metabolism in an animal model of mania
      induced by methamphetamine.
AB  - Studies have shown alterations in mitochondrial complexes of bipolar disorder
      (BD) patients. However, changes in the Krebs cycle enzymes have been little
      studied. The animal model of mania induced by amphetamine has been widely used
      for the study of bipolar mania. The aim of this study is to assess behavioral and
      energy metabolism changes in an animal model of mania induced by methamphetamine
      (m-AMPH). Wistar rats were first given m-AMPH or saline for 14 days, and then,
      between days 8 and 14, rats were treated with lithium (Li), valproate (VPA), or
      saline (Sal). Locomotor behavior was assessed using the open-field task and
      activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase),
      mitochondrial respiratory chain complexes (I, II, III, and IV), and creatine
      kinase measured in the brain structures (prefrontal, amygdala, hippocampus, and
      striatum). Li and VPA reversed m-AMPH-induced hyperactivity. The administration
      of m-AMPH inhibited the activities of Krebs cycle enzymes and complexes of the
      mitochondrial respiratory chain in all analyzed structures. Li and VPA reversed m
      AMPH-induced energetic metabolism dysfunction; however, the effects of Li and VPA
      were dependent on the brain region analyzed. From the results obtained in this
      study, we suggested that the decreased Krebs cycle enzymes activity induced by m
      AMPH may be inhibiting mitochondrial respiratory chain complexes. Therefore,
      changes in the Krebs cycle enzymes may also be involved in BD.

PMID- 23010384
TI  - Staphylococcus aureus carrying divergent mecA homologue (mecA LGA251) isolated
      from a free-ranging wild bird.

PMID- 23010383
TI  - Operant psychostimulant self-administration in a rat model of depression.
AB  - Depression and psychostimulant addiction are co-morbid conditions; depression is
      a significant risk factor for psychostimulant abuse, and the rate of depression
      in drug addicts is higher than in the general population. Despite the prevalence
      of this comorbidity, there are few animal models examining psychostimulant abuse
      behaviors in depression. We have shown previously that while rats selectively
      bred for depression-like phenotypes (SwLo) have blunted mesolimbic dopamine (DA)
      signaling and locomotor responses to dopaminergic drugs, they voluntarily
      administer excessive amounts of psychostimulants compared to normal or depression
      resistant (SwHi) rats in oral consumption paradigms. To determine whether this
      increased drug intake by depression-sensitive rats extends to operant self
      administration, we assessed fixed ratio-1, progressive ratio, extinction, and
      reinstatement responding for cocaine and amphetamine in SwLo and SwHi rats.
      Contrary to the oral consumption results, we found that the SwHi rats generally
      responded more for both cocaine and amphetamine than the SwLo rats in several
      instances, most notably in the progressive ratio and reinstatement tests. Food
      primed reinstatement of food seeking was also elevated in SwHi rats. These
      results provide further insight into the neurobiology of depression and addiction
      comorbidity and caution that oral and operant psychostimulant self-administration
      paradigms can yield different, and this case, opposite results.

PMID- 23010385
TI  - A novel strategy for intrastriatal dopaminergic cell transplantation: sequential
      "nest" grafting influences survival and behavioral recovery in a rat model of
      Parkinson's disease.
AB  - Neural transplantation in experimental parkinsonism (PD) is limited by poor
      survival of grafted embryonic dopaminergic (DA) cells. In this proof-of-principle
      study we hypothesized that a first regular initial graft may create a
      "dopaminergic" environment similar to the perinatal substantia nigra and
      consequently stimulate a subsequent graft. Therefore, we grafted ventral
      mesencephalic neurons sequentially at different time intervals into the same
      target localization. Rats with a unilateral lesion of the dopamine neurons
      produced by injections of 6-hydroxydopamine (6-OHDA) received E14 ventral
      mesencephalon derived grafts into the DA-depleted striatum. In the control group
      we grafted all 6 deposits on the first day (d0). The other 4 groups received four
      graft deposits distributed over 2 implantation tracts followed by a second
      engraftment injected into the same site 3, 6, 14 and 21 days later. Quantitative
      assessment of the survival of tyrosine hydroxylase-immunoreactive neurons and
      graft volume revealed best results for those DA grafts implanted 6 days after the
      first one. In the present study, a model of short-interval sequential
      transplantation into the same target-site, so called "nest" grafts were
      established in the 6-OHDA rat model of PD which might become a useful tool to
      further elucidate the close neurotrophic and neurotopic interactions between the
      immediate graft vicinity and the cell suspension graft. In addition, we could
      show that the optimal milieu was established around the sixth day after the
      initial transplantation. This may also help to further optimize current
      transplantation strategies to restore the DA system in patients with PD.

PMID- 23010386
TI  - Raising the bar.

PMID- 23010387
TI  - Switching of anti-TNF-alpha agents in Behcet's disease.
AB  - OBJECTIVES: Recent reports suggest efficacy of anti-tumour necrosis factor-alpha
      (TNF-alpha) therapy in Behcet's disease. However, the switching of anti-TNF-alpha
      agents for treatment failure remains unexplored. Our aims were to describe the
      efficacy and safety of a second anti-TNF-alpha agent in Behcet's disease patients
      after failure of a first agent. METHODS: In this retrospective case series, 34
      Behcet's disease patients receiving anti-TNF-alpha agents, 19 of whom switched to
      a second anti-TNF-alpha agent, were identified. We assessed the response to anti
      TNF-alpha agents, the duration of anti-TNF-alpha therapy, the reasons for
      withdrawal, adverse events, the Behcet's Disease Current Activity Form (BDCAF), C
      reactive protein (CRP), ESR and concomitant therapies at the onset of the first
      and second anti-TNF-alpha therapies, and after 6, 12 and 24 months. RESULTS:
      Clinical improvements were seen in 26/34 (76%) after the first and 18/19 (95%)
      after the second anti-TNF-alpha agent. Continuation rates at 24 months were 14.4%
      after the first and 22.3% after the second anti-TNF-alpha agent. The most
      frequent reason for discontinuation was secondary failure in both groups (12
      after the first anti-TNF-alpha agent and 8 after the second). Adverse events
      leading to treatment withdrawal were seen in 10 after the first anti-TNF-alpha
      agent and three after the second. CONCLUSIONS: [corrected] The second anti-TNF
      alpha agent in Behcet's disease demonstrated similar efficacy to that seen with
      the first agent without new safety concerns, supporting switching to a second
      anti-TNF-alpha agent. However, long-term continuation rates for anti-TNF-alpha
      therapy were low after both the first and second agents.

PMID- 23010388
TI  - Cyto-genotoxic effects of smoke from commercial filter and non-filter cigarettes
      on human bronchial and pulmonary cells.
AB  - Cigarette smoke is a complex mixture of chemicals, some of which are known as
      carcinogens. The cyto-genotoxic effects of cigarette-smoke extract (CSE) from
      commercial cigarettes without (A and B) and with filter (C and D) were evaluated
      at different CSE concentrations on A549 and BEAS-2B cells. The particle content
      of the cigarette smoke and the metal composition of the CSE were also analyzed.
      The cells were exposed to 1-10% of the CSE from one cigarette per experiment.
      Cytotoxicity was evaluated by use of the MTT assay after 24h, and the lactate
      dehydrogenase (LDH) assay after 30min and 24h. The Fpg-modified comet assay was
      used to evaluate direct-oxidative DNA damage on cells exposed for 30min. As
      expected, unfiltered cigarette smoke (particularly from the B cigarette)
      contained a higher number of particles than filtered smoke. With smoke extract
      from the B cigarette we found a decrease in cell viability only in BEAS-2B cells.
      The results of the LDH test showed membrane damage for B-cigarette smoke extract,
      particularly in BEAS-2B cells. Extracts from unfiltered cigarette smoke induced
      significant direct DNA damage, to a larger extent in A549 cells. Filtered
      cigarette-smoke extract induced a significant direct DNA damage at 5-10%. A
      significant induction of oxidative DNA damage was found at the highest CSE
      concentration in both cell types (by smoke extracts from B and C cigarettes in
      A549 cells, and from A and D cigarettes in BEAS-2B cells). Smoke extracts from
      filter cigarettes induced less direct DNA damage than those from unfiltered
      cigarettes in A549 cells, probably due to a protective effect of filter. In BEAS
      2B cells the smoke extract from the B-cigarette showed the highest genotoxic
      effect, with a concentration-dependent trend. These findings show a higher cyto
      genotoxicity for smoke extracts from the B-cigarette and oxidative effects for
      those from the A and D cigarettes, particularly in BEAS-2B cells. Moreover, there
      was a higher responsiveness of A549 cells to genotoxic insult of CSE, and a
      cigarette-dependent genotoxicity in BEAS-2B cells. Our experimental model
      demonstrated to be suitable to sensitively detect early genotoxic response of
      different lung-cell types to non-cytotoxic concentrations of complex inhalable
      mixtures.

PMID- 23010389
TI  - Development of histopathological indices in a commercial marine bivalve
      (Ruditapes decussatus) to determine environmental quality.
AB  - Bivalve histopathology is an acknowledged tool in environmental toxicology
      studies, however geographically restricted, limited to a few species and still
      lacking the degree of detail needed to develop effective (semi)quantitative
      approaches. A first-time detailed histopathological screening was performed on
      grooved carpet shell clams collected from commercial shellfish beds in distinct
      coastal ecosystems of the Southern Portuguese coast: two parted sites within an
      impacted estuary (S(1) and S(2)), an inlet channel of a fish farm at a considered
      pristine estuary (site M) and a site allocated in a clean coastal lagoon (A). A
      total of thirty histopathological lesions and alterations were analysed in the
      gills and digestive glands following a weighted condition indices approach,
      including inflammation-related responses, necrosis, neoplastic diseases and
      parasites. Digestive glands were consistently more damaged than gills, except for
      animals collected from site M, where the most severe lesions were found in both
      organs, immediately followed by S(2). Clams from sites S(1) and A were overall
      the least damaged. Neoplastic diseases were infrequent in all cases. Inflammation
      related traits were some of the most common alterations progressing in animals
      enduring severe lesions such as digestive tubule (diverticula) and intertubular
      tissue necrosis. Some alterations, such as lipofuscin aggregates within digestive
      tubule cells, did not relate to histological lesions. Granulocytomas only
      occurred in heavily infected tissues. Animals from M and A presented the highest
      infections in the digestive gland, especially by protozoa. Gill infections were
      more similar between sites. Still, the level of infection does not account for
      all histopathological lesions in either organ. Overall, the results are in
      accordance with environmental parameters, such as distance to pollution sources,
      sediment type and hydrodynamics, and show that the combination of multiple
      histopathological features in these clams provides good sensitivity for inter
      site distinction even when low or moderate anthropogenic impacts are at stake.

PMID- 23010390
TI  - Ciliate Nassula sp. grazing on a microcystin-producing cyanobacterium
      (Planktothrix agardhii): impact on cell growth and in the microcystin fractions.
AB  - The proliferation of microcystins (MCs)-producing cyanobacteria (MCs) can have
      detrimental effects on the food chain in aquatic environments. Until recently,
      few studies had focused on the fate of MCs in exposed organisms, such as primary
      consumers of cyanobacteria. In this study, we investigate the impact of an MC
      producing strain of the cyanobacterium Planktothrix agardhii on the growth and
      physiology of a Nassula sp. ciliate isolated from a non-toxic cyanobacterial
      bloom. We show that this Nassula sp. strain was able to consume and grow while
      feeding exclusively on an MC-producing cyanobacterium over a prolonged period of
      time (8 months). In short-term exposure experiments (8 days), ciliates consuming
      an MC-producing cyanobacterial strain displayed slower growth rate and higher
      levels of antioxidant enzymes than ciliates feeding on two non-MC-producing
      strains. Three high-performance methods (LC/MS, LC/MS-MS and ELISA) were used to
      quantify the free and bound MCs in the culture medium and in the cells. We show
      that ciliate grazing led to a marked decrease in free MCs (methanol extractable)
      in cells, the MCs were therefore no longer found in the surrounding culture
      medium. These findings suggest that MCs may have undergone redistribution (free
      vs bound MCs) or chemical degradation within the ciliates.

PMID- 23010391
TI  - Enzymatic GST levels and overall health of mullets from contaminated Brazilian
      Lagoons.
AB  - Glutathione S-transferase (GST) assays in non-mammalian organisms are usually
      conducted inappropriately, since no previous standardization of the optimal
      concentrations of proteins and substrates and adequate pH is conducted.
      Standardization is a key task to adjust enzyme assays at their kinetically
      correct maximal initial velocities, if one wants these velocities to indicate the
      amount of enzyme in a sample. In this paper GST assays were standardized in liver
      cytosol to compare seasonal GST levels in liver of mullet from two contaminated
      lagoons in the Rio de Janeiro to those from a reference bay. GST potential as a
      biomarker of sublethal intoxication in this species was also evaluated. Mullet
      liver GST levels assayed with substrates that corresponded to three different GST
      isoenzymes varied throughout the year. The differences indicated that mullets are
      suffering from sublethal intoxication from contaminants in these lagoons.
      Seasonal variations of activity were relevant, since these could indicate
      differences in xenobiotic input into the areas. An analysis of overall mullet
      health condition using a morphological index (the Fulton Condition Factor) and
      macroscopic abnormalities corroborated the differences in GST levels, with fish
      from one of the sites in worse overall health condition showing lower and
      significantly different FCF when compared to the reference site. Therefore, GST
      standardized activity levels are useful biomarkers of environmental contamination
      for mullet.

PMID- 23010392
TI  - Changes in trace elements during lactation in a marine top predator, the grey
      seal.
AB  - Lactation in pinnipeds represents the most significant cost to mothers during the
      reproductive cycle. Dynamics of trace elements and their mobilization associated
      with energy reserves during such an intense physiological process remains poorly
      understood in marine mammals. The changes in tissue concentrations of 11 elements
      (Ca, Cd, Cr, Cu, Fe, Hg, Ni, Pb, Se, V, and Zn) were investigated in a
      longitudinal study during the lactation period and during the post-weaning fast
      period. Blood, milk, blubber, and hair samples were collected sequentially from
      21 mother-pup pairs of grey seals (Halichoerus grypus) from the Isle of May in
      Scotland. Maternal transfer through the milk was observed for all trace elements,
      except for Cd. As an indicator of the placental transfer, levels in pup lanugo
      (natal coat) revealed also the existence of maternal transfer and accumulation of
      all assayed trace elements during the foetal development. The placental and
      mammary barriers against non-essential metal transfer to offspring appear to be
      absent or weak in grey seals. Examining the contamination levels showed that this
      grey seal population seems more highly exposed to Pb than other phocid
      populations (2.2 mg/kg dw of grey seal hair). In contrast, blood and hair levels
      reflected a lower Hg exposure in grey seals from the Isle of May than in harbour
      seals from the southeastern North Sea. This study also showed that trace element
      concentrations in blood and blubber could change rapidly over the lactation
      period. Such physiological processes must be considered carefully during
      biomonitoring of trace elements, and potential impacts that rapid fluctuations in
      concentrations can exert on seal health should be further investigated.

PMID- 23010393
TI  - Maintaining long-term adherence to lifestyle interventions for cognitive health
      in late life.

PMID- 23010396
TI  - [Second review for lymphoma diagnosis. A clinical point of view].

PMID- 23010397
TI  - [Second expert review on lymphoma: assessment of a one year activity in a general
      hospital].
AB  - A standardized second histological review for lymphomas was established by the
      French National Cancer Institute in 2010. The objective of our study was to
      assess the clinical impact of this process between a general hospital (reader 1)
      and an expert (reader 2). This prospective study was conducted between April 1st
      2010 and April 1st 2011. Fifty-four cases of lymphoma were subjected to an expert
      review following the "LYMPHOPATH" recommendations and diagnoses of readers 1 and
      2 were compared according to the WHO 2008 classification of lymphomas. We
      distinguished serious discrepancies (lymphoma versus other malignancy) from
      subtyping disagreement with or without impact on therapeutic strategy. We also
      determined the delays between the initial reception of the sample and reader 1's
      (period A) and reader 2's (period B) reports, respectively. Any additional
      analysis performed by second reader was also reported. Our study revealed one
      case of subtyping discordance (1.85%). The mean delays were 7 days for period A
      and 20 days for period B, respectively. Additional immunohistochemical techniques
      were requested by reader 2 in 11 cases (20.4%). These data provide evidence to
      suggest that in our department, a second review targeted on difficult diagnoses,
      rare lymphomas or when further analyses are required would be more relevant than
      a standardized second review.

PMID- 23010398
TI  - [A silent-growing and fast-killing melanoma in a teenager].
AB  - Malignant melanoma is a relatively rare but potentially aggressive tumor in
      children and adolescents. We report the case of a metastatic malignant melanoma
      in a 17-year-old girl, first diagnosed on cytological features of a fine-needle
      lymph node aspiration and then histologically confirmed by both examination of
      the metastatic adenopathy and a clinically harmless skin lesion of the scalp,
      which harbored focal microscopic pattern of melanoma. A fluorescent in situ
      hybridization study revealed that both metastatic and primary cutaneous tumours
      contained the same and pejorative chromosomal aberration consisting in CCND1
      amplification (11q13). This observation raises actual limits and challenges in
      the fields of diagnosis and treatment of fast-killing melanomas.

PMID- 23010399
TI  - [Telangiectatic osteosarcoma secondary to a liposclerosing myxofibrous tumor: a
      case report].
AB  - Malignant transformation of a fibrous dysplasia into an osteosarcoma is very
      rare. We report the case of an 84-year-old man with telangiectatic osteosarcoma
      of the upper femur arising in a previous fibrous dysplasia also known as
      liposclerosing myxofibrous tumor. The tumor was expressing the epithelial
      membrane antigen. This is the first described case of a malignant transformation
      into an osteosarcoma arising in a liposclerosing myxofibrous tumor. We discuss
      the main differential diagnosis with a review.

PMID- 23010401
TI  - [Retroperitoneal bronchogenic cyst].
AB  - Bronchogenic cysts are benign lesions, which are usually described at the chest
      level. We present here a case report of a retroperitoneal bronchogenic cyst. A 77
      year-old man presented with a left retroperitoneal tumor discovered by scanner.
      There was no endocrine disruption. Excision of the lesion was performed and final
      diagnosis was a bronchogenic cyst. Current widespread use of modern radiology
      enables increased discovery of such "incidentalomes". In the future, pathologists
      will be routinely faced with this type of diagnosis, which up to now has been
      described as exceptional.

PMID- 23010400
TI  - [Q fever: bone marrow characteristic granuloma].
AB  - Q fever is a worldwise zoonosis, caused by an obligate intracellular bacterium,
      Coxiella burnetii. In humans, acute disease, when symptomatic, can manifest by a
      flu-like illness, pneumonia or hepatitis. Patients with predisposing conditions
      can evolve with chronic disease, which major clinical presentation is
      endocarditis with negative routine blood cultures. Histological studies of Q
      fever based on infected organs biopsies (liver and bone marrow) have demonstrated
      a distinctive type of granuloma, typically appearing as a "doughnut" granuloma,
      characterized by a central clean space surrounded by inflammatory cells and
      rimmed with an eosinophilic fibrinoid material. We describe a 37-year-old man,
      admitted to hospital for persistent fever. Bone marrow biopsy showed the
      characteristic "doughnut" granuloma, suggesting a Q fever. Diagnosis was then
      confirmed by serological tests for C. burnetii.

PMID- 23010402
TI  - [Eosinophilic angiocentric fibrosis: a form of IgG4-related systemic disease?].
AB  - Eosinophilic angiocentric fibrosis is a rare fibro-inflammatory disorder of
      unknown etiology with only 40 cases reported in the literature. It primarily
      affects the sinonasal tract and more rarely the orbit, the larynx and the gums.
      This benign disorder is characterized by a slowly progressive process mimicking a
      tumor, with frequent recurrences after surgical excision and cortico-therapy. The
      typical histology consists of fibro-inflammatory lesion with numerous
      eosinophils, arranged in a perivascular pattern. As the lesion matures,
      inflammation becomes less intense and the fibrosis progresses with an onion-skin
      type perivascular fibrosis. A recent paper suggests that EAF is part of the
      spectrum of IgG4-related systemic disease. We report a case of orbital EAF in an
      86-year-old woman which sustained this hypothesis.

PMID- 23010403
TI  - [A peridiverticular colonic granuloma].

PMID- 23010404
TI  - [Vulvar papulpustules and perianal ulcerations].

PMID- 23010405
TI  - [Multiple ulcerative nodules].

PMID- 23010407
TI  - [A lethal multivisceral failure].

PMID- 23010406
TI  - [An unusual native kidney neoplasm presenting in a kidney graft recipient].

PMID- 23010408
TI  - [Mixed ductal endocrine carcinoma of the pancreas].

PMID- 23010409
TI  - [A rare infantile maxillary tumor].

PMID- 23010410
TI  - [Unusual naso-sinusal tumor].

PMID- 23010411
TI  - [Malakoplakia associated with a colonic adenocarcinoma].

PMID- 23010412
TI  - [The role of histopathology investigations in legal medicine].

PMID- 23010414
TI  - Salvage stereotactic body radiotherapy for patients with limited prostate cancer
      metastases: deferring androgen deprivation therapy.
AB  - BACKGROUND: We investigated whether repeated stereotactic body radiotherapy
      (SBRT) of oligometastatic disease is able to defer the initiation of palliative
      androgen deprivation therapy (ADT) in patients with low-volume bone and lymph
      node metastases. PATIENTS AND METHODS: Patients with up to 3 synchronous
      metastases (bone and/or lymph nodes) diagnosed on positron emission tomography,
      following biochemical recurrence after local curative treatment, were treated
      with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation
      therapy-free survival (ADT-FS) defined as the time interval between the first day
      of SBRT and the initiation of ADT was the primary end point. ADT was initiated if
      more than 3 metastases were detected during follow-up even when patients were
      still asymptomatic or in case of a prostate specific antigen elevation above 50
      ng/mL in the absence of metastases. Secondary end points were local control,
      clinical progression-free survival, and toxicity. Toxicity was scored using the
      Common Terminology Criteria for Adverse Events. RESULTS: We treated 24 patients
      with a median follow-up of 24 months. Ten patients started with ADT resulting in
      a median ADT-FS of 38 months. The 2-year local control and clinical progression
      free survival was 100% and 42%, respectively. Eleven and 3 patients,
      respectively, required a second and third salvage treatment for metachronous low
      volume metastatic disease. No grade 3 toxicity was observed. CONCLUSION: Repeated
      salvage SBRT is feasible, well tolerated and defers palliative ADT with a median
      of 38 months in patients with limited bone or lymph node PCa metastases.

PMID- 23010415
TI  - Involvement of endoplasmic reticulum and autophagy in microcystin-LR toxicity in
      Vero-E6 and HepG2 cell lines.
AB  - This work investigates the involvement of the endoplasmic reticulum (ER) and
      autophagy in microcystin-LR (MCLR) toxicity in Vero-E6 and HepG2 cell lines.
      Additionally, morphological alterations induced by MCLR in lysosomes and
      mitochondria were studied. Cytotoxicity evaluation showed that pure MCLR and MCLR
      from LMECYA110 extract induce concentration dependent viability decays after 24h
      exposure. HepG2 cells showed an increased sensitivity to MCLR than Vero cells,
      with lower cytotoxic thresholds and EC(50) values. Conversely, LC3B
      immunofluorescence showed that autophagy is triggered in both cell lines as a
      survival response to low MCLR concentrations. Furthermore, MCLR induced a MCLR
      concentration-dependent decrease of GRP94 expression in HepG2 cells while in Vero
      cells no alteration was observed. This suggests the involvement of the ER in
      HepG2 apoptosis elicited by MCLR, while in Vero cells ER destructuration could be
      a consequence of cytoskeleton inflicted damages. Additionally, in both cell
      lines, lysosomal destabilization preceded mitochondrial impairment which occurred
      at high toxin concentrations. Although not an early cellular target of MCLR,
      mitochondria appears to serve as central mediators of different signaling
      pathways elicited by the organelles involved in MCLR toxicity. As a result,
      kidney and hepatic cell lines exhibit cell type and dose-dependent mechanisms to
      overcome MCLR toxicity.

PMID- 23010416
TI  - Genetic biomarkers of hypertension and future challenges integrating epigenomics.
AB  - Essential hypertension is a multifactorial disease, considered to be one of the
      world's greatest public health problems. Despite recent, major, technical
      advances aiming to elucidate its genetic component, the discovered biomarkers up
      to now were reported to have only small effects, explaining consequently a tiny
      fraction of its phenotypic variance and resulting in a large proportion of
      missing heritability. Likewise, little evidence is available with regard to the
      epigenetic regulation of essential hypertension, since no robust biomarkers have
      yet been reported. In the current review, we discuss the main approaches used
      exclusively to study the genetics and epigenetics of essential hypertension, the
      biomarkers identified, their clinical utility and the difficulties to be
      overcome. Furthermore, we propose a new category of functional genetic-epigenetic
      biomarkers, eMethSNPs, and we provide their hypothetical gene expression profiles
      for a genetic functional regulation of hypertension via DNA methylation. Though
      believed to be infrequent, eMethSNPs could constitute a new category of
      mechanistically-based genetic biomarkers predisposing to essential hypertension.

PMID- 23010417
TI  - Elderly subjects with type 2 diabetes show altered tissue electrical properties.
AB  - OBJECTIVE: The aim of the present research was to show the characteristics of
      body composition in a sample of elderly subjects with type 2 diabetes compared
      with healthy controls matched by age and body mass index (BMI) by bioelectrical
      impedance vector analysis. METHODS: The sample consisted of 144 free-living
      patients (84 women and 60 men) with type 2 diabetes 60 to 84 y old and 209 age
      matched controls (116 women and 93 men). Anthropometric measurements (weight;
      height; upper arm, hip, waist, and calf circumferences; biceps; triceps; and
      subscapular and suprailiac skinfolds) were taken. Blood samples for the
      assessment of plasma glucose and glycated hemoglobin were collected. The BMI,
      upper arm muscular area, and waist-to-hip ratio were calculated. Bioelectrical
      impedance vector analysis was applied. The analysis was performed in the entire
      diabetic sample and the healthy BMI-matched groups. RESULTS: Compared with
      healthy subjects, patients had greater weight (P < 0.01 in women), higher BMI (P
      < 0.01 in women), smaller muscular area (P < 0.01 in men), and thicker skinfolds
      (P < 0.01 in women and men). Female and male patients showed larger phase angles
      (P < 0.01). Moreover, female patients showed a shorter vector length and lower
      resistance (P < 0.01) and male patients showed a higher reactance (P < 0.01). The
      BMI-matched analysis confirmed that patients were characterized by larger phase
      angles. CONCLUSIONS: Older patients with type 2 diabetes were characterized by
      peculiar anthropometric and bioelectrical patterns, which can be related to their
      smaller appendicular muscular area and lower extracellular/intracellular water
      ratio.

PMID- 23010418
TI  - Comparison of eicosapentaenoic acid concentrations in plasma between patients
      with ischemic stroke and control subjects.
AB  - OBJECTIVE: omega-3 fatty acids, including eicosapentaenoic acid (EPA), prevent
      ischemic stroke. However, the clinical importance of EPA for ischemic stroke and
      its subtype has not been fully elucidated. METHODS: In a cross-sectional study,
      we determined whether omega-3 fatty acids were predictive factors for ischemic
      stroke. We compared common clinical parameters among 65 patients with ischemic
      stroke and 65 control subjects. The parameters included blood chemistry data;
      concentrations of EPA, docosahexaenoic acid, and arachidonic acid (AA); EPA/AA
      ratio; smoking; alcohol intake; fish consumption more than four times per week;
      and the incidence of underlying diseases. The comparisons were performed using
      the Mann-Whitney U test, and multiple logistic regression analysis was applied to
      the significant factors in the non-parametric test. We also applied the same
      approach to the ischemic stroke subtypes, cardioembolism and large-artery
      atherosclerosis. RESULTS: In the multiple logistic regression analysis after the
      Mann-Whitney U test, a lower EPA concentration was one of the significant risk
      factors for ischemic stroke, as were a lower body mass index, lower high-density
      lipoprotein cholesterol, and smoking (sensitivity 0.846, specificity 0.831,
      positive predictive value 0.833). In the analysis of subtypes, a lower EPA/AA
      ratio and a lower body mass index were the significant risk factors for
      cardioembolism (sensitivity 0.800, specificity 0.733, positive predictive value
      0.750). However, large-artery atherosclerosis was not related to the EPA
      concentration or the EPA/AA ratio. CONCLUSIONS: In this study, the plasma EPA
      concentration and the EPA/AA ratio were potential predictive risk factors for
      ischemic stroke, especially for cardioembolism. Further prospective studies are
      necessary.

PMID- 23010419
TI  - Effects of weight loss from a high-calcium energy-reduced diet on biomarkers of
      inflammatory stress, fibrinolysis, and endothelial function in obese subjects.
AB  - OBJECTIVE: Obesity is characterized by chronic subclinical inflammation, which is
      critical to endothelial dysfunction. Weight loss, induced by lifestyle
      interventions, is associated with a decline in biomarkers of inflammation and
      endothelial dysfunction. There is little evidence that high dietary calcium
      intake may reduce inflammation and improve endothelial function. The purpose of
      this study was to evaluate the effects of weight loss from a high-calcium energy
      reduced diet on biomarkers of inflammation, fibrinolysis, and endothelial
      function in obese individuals. METHODS: In this randomized clinical trial, we
      analyzed the data from 35 obese adults who lost at least 3% of initial body
      weight, during a period of 16 wk of energy restriction (-800 Kcal/d). Individuals
      were randomized into the following dietary regimens: (1) a high calcium diet
      (HCD; 1200-1300 mg/d) or (2) a low-calcium diet (LCD; <500 mg/d). RESULTS: After
      16 wk of intervention subjects on HCD compared with those on LCD exhibited
      greater reduction in waist circumference and waist-to-hip ratio. Participants on
      HCD presented a significant reduction in all biomarkers of endothelial
      dysfunction evaluated in the study (intracellular adhesion molecule-1, vascular
      cell adhesion molecule 1, and E-Selectin), whereas subjects on LCD showed a
      significant decrease in intracellular adhesion molecule-1 and E-Selectin.
      Biomarkers of inflammation and fibrinolysis were reduced in both diets, although
      without reaching statistical significance. The reduction in all markers of
      inflammation, fibrinolysis, and endothelial dysfunction was similar in both
      diets. CONCLUSION: The findings of this study suggest that increased calcium
      intake during weight loss has no benefits with respect to biomarkers of
      inflammation, fibrinolysis, and endothelial function.

PMID- 23010420
TI  - Selenium blood concentrations in patients undergoing elective cardiac surgery and
      receiving perioperative sodium selenite.
AB  - OBJECTIVES: We recently reported that cardiac surgical patients in our
      institution exhibited low selenium blood levels preoperatively, which were
      further aggravated during surgery and independently associated with the
      development of postoperative multiorgan failure. Low circulating selenium levels
      result in a decreased antioxidant capacity. Both can be treated effectively by
      sodium-selenite administration. Little is known about the kinetics of exogenously
      administered sodium-selenite during acute perioperative oxidative stress. The aim
      of this study was to assess the effects of perioperative high-dose sodium
      selenite administration on selenium blood concentrations in cardiac surgical
      patients. METHODS: One hundred four cardiac surgical patients were enrolled in
      this prospective observational trial. Patients received an intravenous bolus of
      2000 MUg selenium after an induction of anesthesia and 1000 MUg selenium every
      day further during their intensive care unit (ICU) stay. Selenium blood levels
      were measured at regular intervals. RESULTS: Preoperative sodium-selenite
      administration increased selenium blood concentrations to normal values on ICU
      admission, but failed to prevent a significant decrease of circulating selenium
      on the first postoperative day. During the further ICU stay, selenium blood
      levels were normalized by the administration strategy and did not exceed the
      German reference range. No acute selenium-specific side effects occurred. When
      matching the participating patients to a historical control group without sodium
      selenite administration, the chosen strategy was associated with a decrease in
      SAPS II (23 +/- 7 versus 29 +/- 8, P = 0.005) and SOFA scores (4 +/- 3 versus 7
      +/- 2, P = 0.007) on the first postoperative day, but was unable to improve the
      postoperative outcome in patients staying >1 d in ICU. CONCLUSIONS: Despite
      preemptive high-dose sodium-selenite administration, cardiac surgical patients
      experienced a significant decrease in circulating selenium levels on the first
      postoperative day.

PMID- 23010421
TI  - [Dorsi elastofibroma. About 14 cases, and review of the literature].
AB  - Elastofibroma dorsi is a benign tumor which usually occurs at the inferior angle
      of the scapula. We retrospectively reviewed 14 cases of elastofibroma dorsi, in
      nine patients. The patients were hospitalized in the departments of plastic
      surgery, orthopedic surgery or visceral surgery. Mean age was 67 years. The
      location of the lesions (bilateral in five patients) was typical, in the
      thoracoscapular region. Nine lesions were removed surgically, six shoulders were
      asymptomatic after surgery. Elastofibroma is a rare, slow-growing lesion. It
      occurs in connective tissue of the infrascapular region of elderly patients. The
      pathogenesis of the lesion still remains unclear. MRI and computed tomography are
      useful for assessment of elastofibroma dorsi, and can potentially help avoid the
      need for unnecessary biopsy and surgery, especially in the asymptomatic patient.
      It should be surgically removed only in symptomatic patients. 

PMID- 23010422
TI  - Blockade of orexin receptor 1 attenuates the development of morphine tolerance
      and physical dependence in rats.
AB  - The goals of this study were to evaluate the effects of pretreatment by orexin
      receptor-1 antagonist on the development of morphine tolerance and physical
      dependence in rat. Animals were rendered dependent on morphine by subcutaneous
      (SC) injection of morphine sulfate (10mg/kg) at set intervals of 12h for 10days.
      Just before the morphine administration, the animals received SB-334867, a
      selective orexin receptor 1 (OXR1) antagonist. To assess morphine tolerance, the
      antinociceptive responses of morphine were measured using the warm-water tail
      immersion test before and after its administration. On day 11, naloxone was
      injected 2h after morphine administration and the physical dependence evaluated
      by quantifying/scoring naloxone-precipitated withdrawal signs for 30min. The
      effect of chronic SB-334867 on locomotion was carried out by calculating the
      number of grid crossings as a measure of locomotor activity. Our findings
      demonstrated that although morphine-tolerance tended to develop in response to
      repeated injections of morphine, pre-treatment of OXR1 antagonist prevented this
      effect, causing a delay in the development of morphine-tolerance. Moreover, co
      administration of orexin receptor 1 antagonist with morphine significantly
      decreased the somatic signs of withdrawal including diarrhea, teeth chattering,
      jumping, and defecation. Administration of SB-334867 alone or in a chronic co
      administration with morphine failed to change locomotor activity. These results
      suggest that the activation of OXR1 might be involved in the development of
      morphine tolerance and dependence.

PMID- 23010423
TI  - Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c
      mice: low doses induce hypolocomotion.
AB  - The overall goal of the present study was to determine the effects of different
      doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four
      experiments were designed to test a wide range of meth doses in BALB/c female
      mice. In Experiment 1, we examined locomotor activity induced by an acute
      administration of low doses of meth (0.01 and 0.03mg/kg) in a 90-min session.
      Experiment 2 was conducted to test higher meth doses (0.3-10mg/kg). In Experiment
      3, separate sets of mice were pre-treated with various meth doses once or twice
      (one injection/week) prior to a locomotor challenge with a low meth dose.
      Finally, in Experiment 4, we tested whether locomotor activation would be
      affected by pretreatment with a low or moderate dose of meth one month prior to
      the low meth dose challenge. Results show that low doses of meth induce
      hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior
      exposure to either one moderate or high dose of meth or to two, low doses of meth
      attenuated the hypolocomotor effect of a low meth dose one week later. This
      effect was also attenuated in mice tested one month after administration of a
      moderate meth dose. These results show that low and high doses of meth can have
      opposing effects on locomotor activity. Further, prior exposure to the drug leads
      to tolerance, rather than sensitization, of the hypolocomotor response to low
      meth doses.

PMID- 23010424
TI  - Induction of osteoclastogenesis in an in vitro model of Gaucher disease is
      mediated by T cells via TNF-alpha.
AB  - Gaucher disease is a lysosomal storage disorder caused by deficiency of
      glucocerebrosidase enzymatic activity leading to accumulation of its substrate
      glucocerebrosidase mainly in macrophages. Skeletal disorder of Gaucher disease is
      the major cause of morbidity and is highly refractory to enzyme replacement
      therapy. However, pathological mechanisms of bone alterations in Gaucher disease
      are still poorly understood. We hypothesized that cellular alteration in Gaucher
      disease produces a proinflammatory milieu leading to bone destruction through
      enhancement of monocyte differentiation to osteoclasts and osteoclasts resorption
      activity. Against this background we decided to investigate in an in vitro
      chemical model of Gaucher disease, the capacity of secreted soluble mediators to
      induce osteoclastogenesis, and the mechanism responsible for this phenomena. We
      demonstrated that soluble factors produced by CBE-treated PBMC induced
      differentiation of osteoclasts precursors into mature and active osteoclasts that
      express chitotriosidase and secrete proinflammatory cytokines. We also showed a
      role of TNF-alpha in promoting osteoclastogenesis in Gaucher disease chemical
      model. To analyze the biological relevance of T cells in osteoclastogenesis of
      Gaucher disease, we investigated this process in T cell-depleted PBMC cultures.
      The findings suggest that T cells play a role in osteoclast formation in Gaucher
      disease. In conclusion, our data suggests that in vitro GCASE deficiency, along
      with concomitant glucosylceramide accumulation, generates a state of
      osteoclastogenesis mediated in part by pro-resorptive cytokines, especially TNF
      alpha. Moreover, T cells are involved in osteoclastogenesis in Gaucher disease
      chemical model.

PMID- 23010425
TI  - Molecular cloning and characterization of the anti-obesity gene adipose in pig.
AB  - Obesity has become an epidemic health problem characterized by aberrant energy
      metabolism. As the major player in energy homeostasis, adipose tissue has a
      decisive role in the development of obesity. Many genes involved in adipogenesis
      are also correlated with obesity. Adipose (Adp) has been established as an anti
      obesity gene to repress adipogenesis and fat accumulation in mice, which inhibits
      the transcriptional activity of PPARgamma by forming a chromatin remodeling
      complex with histones and HDAC3. Here, we reported the cloning and
      characterization of the pig Adp gene. Pig Adp cDNA had an ORF of 2034 nucleotides
      and was highly conserved among various species. Genomic sequence analysis
      indicated that pig Adp gene contains 16 exons and 15 introns, spanning more than
      60kb on chromosome 6q21-24. The expression of pig Adp was high in testis, lung,
      kidney and adipose tissues, and relatively low in skeletal muscle. Bioinformatic
      analysis of 5'-flanking region of Adp has identified several potential binding
      sites for pivotal transcriptional factors related to both adipocyte
      differentiation and inflammation, highlighting the significance of Adp in energy
      metabolism. We have confirmed that KLF6, a positive regulator of adipogenesis,
      can enhance the promoter activity of Adp and up-regulate its mRNA expression.
      Taken together, our results would be helpful for further study of Adp regulation
      in the process of fat accumulation.

PMID- 23010426
TI  - Deep brain stimulation lead fixation after Stimloc failure.
AB  - We report a method for deep brain stimulation (DBS) lead fixation in the event
      that the primary anchoring device fails to function effectively. The method
      involves the application of a titanium microplate to secure the lead to the
      skull, thereby providing a fast and reliable "rescue" mechanism for lead
      fixation. This method can supplement any burr hole cap and fixation method.
      Furthermore, this method has several advantages over removal and replacement of
      the primary anchor, such as a lower possibility of lead migration, faster
      procedural time, and cost-effectiveness.

PMID- 23010427
TI  - Endovascular management of sigmoid sinus dural arteriovenous fistula associated
      with sinus stenosis in an infant.
AB  - A 4-month-old female presented with a dural arteriovenous fistula (DAVF), which
      was successfully managed using endovascular techniques. There are very few case
      series reporting DAVF in infants younger than 12 months and, to our knowledge,
      only 60 pediatric patients with DAVF have been reported to date. Although most
      DAVF have a benign course, they can result in life-threatening hemorrhage.
      Endovascular therapies are usually indicated in the management of these
      neurosurgical vascular malformations. Endovascular therapy of DAVF in neonatal
      patients presents some major issues. Gaining arterial access may be problematic
      in femoral arteries too small for the introduction of a sizeable guiding
      catheter. The volumes of contrast and infused fluids must be carefully monitored
      to prevent fluid overload. Radiation exposure should be restricted as far as
      possible. This report contributes to the limited body of evidence on neonatal
      DAVF and its endovascular management.

PMID- 23010428
TI  - Anatomy of the petrous apex as related to the endoscopic endonasal approach.
AB  - The endoscopic endonasal approach (EEA) has been reported to be an efficient
      approach for treating lesions of the petrous apex. However, there have been only
      limited anatomic studies for the EEA. Furthermore, most of the relevant distances
      for EEA cannot be measured easily on a cadaveric skull. Two fresh adult cadaver
      heads and five formalin-fixed adult cadaver heads were dissected using the EEA to
      identify groups of landmarks for safe guidance during this approach. The
      distances between these landmarks were then measured by CT angiography by using
      three-dimensional software. The EEA to the petrous apex can be divided into five
      phases. In each phase, a group of landmarks, rather than a single landmark, can
      be identified easily for guiding the next phase of the approach. There was no
      significant difference between males and females in any of the distances reported
      in the present study. The EEA can be performed to manage a petrous apex lesion
      more safely by referring to multiple landmarks and the distances between them.

PMID- 23010429
TI  - Clinical and radiologic spectrum of corpus callosum infarctions: clues to the
      etiology.
AB  - Infarctions of the corpus callosum are rare. The clinical picture varies from an
      acute onset to slow evolving symptoms, frequently with poor localizing signs;
      however, the location of the infarct in the callosum often correlates with a
      specific etiology. We describe three patients with varying degrees of callosal
      infarction, each corresponding to a particular etiology.

PMID- 23010430
TI  - Scrub typhus associated with transient parkinsonism and myoclonus.
AB  - Parkinsonism with myoclonus is rarely associated with infectious disease in
      adults. We present a 55-year-old man experiencing acute onset bilateral limb
      tremor, rigidity, and myoclonus with small-stepped gait, and skin rash involving
      the trunk and limbs, after a fever. Serum was positive for anti-Orientia
      tsutsugamushi immunoglobulin M antibody. Brain MRI revealed no abnormalities. The
      fever improved with oral doxycycline, and the parkinsonism and myoclonus improved
      with amantadine and clonazepam. This is a rare case of parkinsonism with myolonus
      associated with scrub typhus infection.

PMID- 23010431
TI  - Temporal development of genetic and metabolic effects of biotin deprivation. A
      search for the optimum time to study a vitamin deficiency.
AB  - Biotin deficiency (Bt-D) is usually studied at the point at which the animal
      model exhibits the signs of full-blown deficiency symptoms; in rats, this
      typically occurs at 6-8 weeks of feeding a deficient diet. To differentiate
      specific deficiency effects from those of undernutrition, biotin sufficient and
      deficient rats were studied at 2, 3, 4, and 5 weeks on the deficiency diet,
      before the onset of weight loss and deficiency signs. The deficiency state was
      confirmed by biochemical and molecular analyses. Blood and liver metabolites were
      determined and western blots of signaling proteins, and qRT-PCR gene expression
      studies. The main effects of Bt-D were already well established by the fourth
      week on the diet; thus, we consider the fourth week as the optimum time to study
      the consequences of biotin depletion. Early effects, which were already apparent
      at week 2, included cellular energy deficit (as assessed by increased AMP/ATP
      ratio), activation of the AMPK energy sensor, and changes of carbon metabolism
      gene transcripts (e.g., phosphoenolpyruvate carboxykinase, carnitine palmitoyl
      transferase 1, liver glucokinase and fatty acid synthetase). Reduced post
      prandial blood concentrations of glucose were also observed early; we speculate
      that these are attributable to augmented sensitivity to insulin and increased
      glucose utilization, a likely effect of AMPK induction of translocation of
      glucose transporter GLUT4 to the cell membranes and increased hexokinase
      expression. Other late-onset changes (week 4) included increased serum
      concentrations of lactate and free fatty acids and decreased liver glycogen and
      serum concentrations of triglycerides and total cholesterol. The identification
      of the early specific molecular and metabolic disturbances of biotin deficiency
      might be useful in identifying individuals with marginal deficiency of this
      vitamin, which appears to be common in normal human pregnancy. The study of time
      course of other vitamin deficiencies, such as this one, might help to better
      understand and cope with their effects.

PMID- 23010432
TI  - A novel homozygous mutation in SUCLA2 gene identified by exome sequencing.
AB  - Mitochondrial disorders with multiple mitochondrial respiratory chain (MRC)
      enzyme deficiency and depletion of mitochondrial DNA (mtDNA) are autosomal
      recessive conditions due to mutations in several nuclear genes necessary for
      proper mtDNA maintenance. In this report, we describe two Italian siblings
      presenting with encephalomyopathy and mtDNA depletion in muscle. By whole exome
      sequencing and prioritization of candidate genes, we identified a novel
      homozygous missense mutation in the SUCLA2 gene in a highly conserved aminoacid
      residue. Although a recurrent mutation in the SUCLA2 gene is relatively frequent
      in the Faroe Islands, mutations in other populations are extremely rare. In
      contrast with what has been reported in other patients, methyl-malonic aciduria,
      a biomarker for this genetic defect, was absent in our proband and very mildly
      elevated in her affected sister. This report demonstrates that next-generation
      technologies, particularly exome-sequencing, are user friendly, powerful means
      for the identification of disease genes in genetically and clinically
      heterogeneous inherited conditions, such as mitochondrial disorders.

PMID- 23010433
TI  - EPI-743 reverses the progression of the pediatric mitochondrial disease-
      genetically defined Leigh Syndrome.
AB  - BACKGROUND: Genetically defined Leigh syndrome is a rare, fatal inherited
      neurodegenerative disorder that predominantly affects children. No treatment is
      available. EPI-743 is a novel small molecule developed for the treatment of Leigh
      syndrome and other inherited mitochondrial diseases. In compassionate use cases
      and in an FDA Expanded Access protocol, children with Leigh syndrome treated with
      EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement.
      To confirm these initial findings, a phase 2A open label trial of EPI-743 for
      children with genetically-confirmed Leigh syndrome was conducted and herein we
      report the results. METHODS: A single arm clinical trial was performed in
      children with genetically defined Leigh syndrome. Subjects were treated for 6
      months with EPI-743 three times daily and all were eligible for a treatment
      extension phase. The primary objective of the trial was to arrest disease
      progression as assessed by neuromuscular and quality of life metrics. Results
      were compared to the reported natural history of the disease. RESULTS: Ten
      consecutive children, ages 1-13 years, were enrolled; they possessed seven
      different genetic defects. All children exhibited reversal of disease progression
      regardless of genetic determinant or disease severity. The primary endpoints-
      Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function
      Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant
      improvement (p<0.05). In addition, all children had an improvement of one class
      on the Movement Disorder-Childhood Rating Scale. No significant drug-related
      adverse events were recorded. CONCLUSIONS: In comparison to the natural history
      of Leigh syndrome, EPI-743 improves clinical outcomes in children with
      genetically confirmed Leigh syndrome.

PMID- 23010434
TI  - sCTLA-4, CD4+CD25+Foxp3+ regulatory T cells in Behcet's disease patients.

PMID- 23010436
TI  - Web-based studies: The future in nutritional epidemiology (and overarching
      epidemiology) for the benefit of public health?

PMID- 23010435
TI  - Non-fasting blood glucose and risk of incident coronary heart disease in middle
      aged general population: the Circulatory Risk in Communities Study (CIRCS).
AB  - OBJECTIVE: The objective was to determine whether non-fasting glucose
      concentration is a predictor for incident coronary heart disease. METHODS: We
      investigated a cohort data of 9,900 40- to 69-year-old residents in four Japanese
      communities for 1975-1986 baseline surveys of the Circulatory Risk in Communities
      Study (CIRCS). Non-fasting blood glucose concentrations were available for 7,332
      participants. Diabetic type was defined as a glucose level of >= 11.1 mmol/L
      and/or the use of medication for diabetes mellitus. RESULTS: A total of 170
      coronary heart disease including 113 myocardial infarctions occurred in non
      fasting participants within the median 22-year follow-up period. Multivariable
      hazard ratios (HRs) of incident coronary heart disease for the participants with
      diabetic type compared with the normal type were 1.98 (0.84-4.68) for men, 3.39
      (1.47-7.81) for women, and 2.47 (1.37-4.46) for total subjects. Corresponding HRs
      for myocardial infarction were 2.14 (0.83-5.55), 5.70 (2.21-14.67) and 3.17 (1.65
      6.10), respectively. Multivariable HRs of incident coronary heart disease per one
      standard deviation of serum glucose levels were 1.17 (1.02-1.36), 1.19 (1.03
      1.38), and 1.19 (1.08-1.32), respectively. The corresponding HRs for myocardial
      infarction were 1.18 (1.00-1.38), 1.27 (1.07-1.49) and 1.23 (1.10-1.37).
      CONCLUSION: Non-fasting glucose concentration, either as diagnosis of diabetic
      type or as continuous variable, proved to be an independent predictor for
      incident coronary heart disease in middle-aged general population.

PMID- 23010437
TI  - Low intake of B-vitamins is associated with poor adolescent mental health and
      behaviour.
AB  - OBJECTIVE: The current prevalence of mental health problems in Western
      populations is approximately 20% and half of all adult mental health disorders
      are estimated to originate in adolescence. Diet plays an important role in
      modulating psychological wellbeing and B-vitamins are vital for the synthesis of
      neurotransmitters such as serotonin. We aimed to examine the relationship between
      B-group vitamins and adolescent mental health and behaviour. METHODS: This is a
      cross-sectional analysis of the West Australian Pregnancy Cohort (Raine) Study.
      The 17-year follow-up included collection of a food frequency questionnaire
      allowing B-vitamin intake calculation. Mental health was assessed using the Youth
      Self Report (YSR) which measures total, internalising (withdrawn/depressed) and
      externalising (aggressive/delinquent) behaviour scores. Multiple linear
      regression was used to analyse associations between B-vitamins and mental health
      with adjustment for relevant confounders (n=709). RESULTS: Lower intake of
      vitamins B1, B2, B3, B5, B6, and folate was associated with higher externalising
      behaviour scores (p <= 0.05). Reduced intake of vitamin B6 and folate was
      associated with higher internalising behaviour scores (p <= 0.05). CONCLUSIONS:
      Poor nutrition may contribute to the pathogenesis of mental health problems in
      adolescence. The role of B-vitamins requires further investigation in randomised
      controlled trials.

PMID- 23010438
TI  - Towards more eclectic evidence-based medicine in cancer prevention and control.

PMID- 23010439
TI  - Overweight and reduced heart rate variability in British children: an exploratory
      study.
AB  - OBJECTIVE: To investigate the associations between heart rate variability (HRV)
      and weight status in children. METHOD: Following ethics approval, 182 children
      (87 males, 95 females) aged between 6 and 11 years old (Mean (SD) age 9.1 (1.4)
      years) were assessed for height and body mass from which body mass index (BMI,
      kg/m(2)) was calculated. Data were collected in Central England, March-June 2011.
      Resting HRV was assessed in the supine position. Time domain (RMSSD and pNN50)
      and frequency domain (HF and LF power (ms(2)), LF/HF ratio) measures of HRV were
      calculated. Pearson correlations were used to assess the associations between BMI
      and HRV parameters. Differences in HRV parameters according to gender or weight
      status were analysed using t-tests. RESULTS: BMI was significantly and inversely
      related to RMSSD (r=-0.23, p=0.001) and pNN50 (r=0.20, p=0.008) but not frequency
      domain measures of HRV (p>0.05). Overweight/obese children demonstrated lower HF
      power compared to normal weight children (p=0.02). RMSSD and pNN50 were
      significantly lower in overweight/obese children compared to normal weight
      children (p<0.05). Age was associated with changes in Mean R-R and RMSSD
      (p<0.05). CONCLUSION: This exploratory study suggests that HRV is reduced in
      overweight/obese children.

PMID- 23010440
TI  - Promiscuous activity of arginine:glycine amidinotransferase is responsible for
      the synthesis of the novel cardiovascular risk factor homoarginine.
AB  - Low plasma homoarginine has emerged as a risk marker for cardiovascular disease.
      We exploited cells of a patient with a rare inborn error of metabolism to explore
      potential pathways of homoarginine synthesis, using stable isotopes and mass
      spectrometry. Control lymphoblasts, as opposed to lymphoblasts from an
      arginine:glycine amidinotransferase (AGAT)-deficient patient, were able to
      synthesize homoarginine from arginine and lysine. In contrast, in a patient with
      a deficiency of the urea cycle enzyme argininosuccinate synthase, plasma
      homoarginine was not decreased. We conclude that promiscuous activity of AGAT, a
      key enzyme in creatine synthesis, plays a pivotal role in homoarginine synthesis.

PMID- 23010441
TI  - The role of DNA repair in the pluripotency and differentiation of human stem
      cells.
AB  - All living cells utilize intricate DNA repair mechanisms to address numerous
      types of DNA lesions and to preserve genomic integrity, and pluripotent stem
      cells have specific needs due to their remarkable ability of self-renewal and
      differentiation into different functional cell types. Not surprisingly, human
      stem cells possess a highly efficient DNA repair network that becomes less
      efficient upon differentiation. Moreover, these cells also have an anaerobic
      metabolism, which reduces the mitochondria number and the likelihood of oxidative
      stress, which is highly related to genomic instability. If DNA lesions are not
      repaired, human stem cells easily undergo senescence, cell death or
      differentiation, as part of their DNA damage response, avoiding the propagation
      of stem cells carrying mutations and genomic alterations. Interestingly, cancer
      stem cells and typical stem cells share not only the differentiation potential
      but also their capacity to respond to DNA damage, with important implications for
      cancer therapy using genotoxic agents. On the other hand, the preservation of the
      adult stem cell pool, and the ability of cells to deal with DNA damage, is
      essential for normal development, reducing processes of neurodegeneration and
      premature aging, as one can observe on clinical phenotypes of many human genetic
      diseases with defects in DNA repair processes. Finally, several recent findings
      suggest that DNA repair also plays a fundamental role in maintaining the
      pluripotency and differentiation potential of embryonic stem cells, as well as
      that of induced pluripotent stem (iPS) cells. DNA repair processes also seem to
      be necessary for the reprogramming of human cells when iPS cells are produced.
      Thus, the understanding of how cultured pluripotent stem cells ensure the genetic
      stability are highly relevant for their safe therapeutic application, at the same
      time that cellular therapy is a hope for DNA repair deficient patients.

PMID- 23010442
TI  - Pulmonary vein stenosis after radiofrequency ablation of lone atrial fibrillation
      in an ironman triathlete.

PMID- 23010443
TI  - Community Assessment for Public Health Emergency Response (CASPER) one year
      following the Gulf Coast oil spill: Alabama and Mississippi, 2011.
AB  - BACKGROUND: On April 20, 2010, the Deepwater Horizon drilling unit exploded off
      the coast of Louisiana, resulting in 11 deaths and the largest marine petroleum
      release in history. Previous oil spill disasters have been associated with
      negative mental health outcomes in affected communities. In response to requests
      from Mississippi and Alabama, potential mental health issues resulting from this
      event were identified by implementing a novel use of a Community Assessment for
      Public Health Emergency Response (CASPER) in the months immediately following the
      Gulf Coast oil spill. PURPOSE: This assessment was repeated one year later to
      determine long-term mental health needs and changes. METHODS: A two-stage
      sampling method was used to select households, and a questionnaire including the
      Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance
      System (BRFSS) questions was administered. Weighted cluster analysis was
      conducted, and BRFSS questions were compared to the most recent BRFSS reports and
      the 2010 results. RESULTS: In 2011, 8.8%-15.1% of individuals reported depressive
      symptoms compared to 15.4%-24.5% of individuals in 2010, with 13.2%-20.3%
      reporting symptoms consistent with an anxiety disorder compared to 21.4%-31.5% of
      individuals in 2010. Respondents reporting decreased income following the oil
      spill were more likely to report mental health symptoms compared to respondents
      reporting no change in income. CONCLUSIONS: Overall, mental health symptoms were
      higher in the three assessment areas compared to BRFSS reports, but lower than
      2010 surveys. These results suggest that mental health services are still needed,
      particularly in households experiencing decreased income since the oil spill.

PMID- 23010445
TI  - RNF8 and RNF168 but not HERC2 are required for DNA damage-induced ubiquitylation
      in chicken DT40 cells.
AB  - The ubiquitylation cascade plays an important role in the recruitment of repair
      factors at DNA double-strand breaks. The involvement of a growing number of
      ubiquitin E3 ligases adds to the complexity of the DNA damage-induced ubiquitin
      signaling. Here we use the genetically tractable avian cell line DT40 to
      investigate the role of HERC2, RNF8 and RNF168 in the DNA damage-induced
      ubiquitylation pathway. We show that formation of ubiquitin foci as well as cell
      survival after DNA damage depends on both RNF8 and RNF168. However, we find that
      RNF8 and RNF168 knockout cell lines respond differently to treatment with
      camptothecin indicating that they do not function in a strictly linear manner.
      Surprisingly, we show that HERC2 is required neither for survival nor for
      ubiquitin foci formation after DNA damage in DT40. Moreover, the E3 ubiquitin
      ligase activity of HERC2 is not redundant to that of RNF8 or RNF168.

PMID- 23010446
TI  - Performance characteristics of the ARCHITECT Galectin-3 assay.
AB  - OBJECTIVES: Galectin-3 is an emerging biomarker that is commonly increased in
      patients with heart failure and/or patients at risk for cardiovascular disease.
      We evaluated the Galectin-3 assay on the Abbott ARCHITECT i1000(SR) and ARCHITECT
      i2000(SR) at 2 testing sites. DESIGN AND METHODS: Imprecision (%CV),
      interference, limits of blank (LoB), detection (LoD), and quantitation (LoQ),
      linearity, method comparison to an ELISA method, comparisons between plasma and
      serum, and reference intervals were evaluated. Imprecision was performed based on
      two runs of duplicate testing conducted daily. Verification of LoB, LoD, and LoQ
      was performed according to Clinical and Laboratory Standards Institute
      guidelines. Linearity was evaluated by making 5 dilutions of a high patient EDTA
      plasma pool with a low patient pool. Reference intervals were established using
      EDTA plasma collected from self-reported healthy volunteers. A second lot of
      reagent was used at one site for method comparison and imprecision studies.
      RESULTS: Total CV's were <=6.0%. A positive interference was observed for
      hemolyzed samples over 2.0 g/L hemolysate. The LoB ranged from 0.1 to 0.3 ng/mL,
      the LoD from 1.4 to 2.1 ng/mL and the LoQ from 3.0 to 3.3 ng/mL. Linearity
      studies had slopes and correlation coefficients equal to 1.0. Comparison of the
      i1000(SR) and i2000(SR) to the ELISA method demonstrated slopes of 1.0 to 1.2 and
      correlation coefficients of 0.93 to 0.97. The 97.5th percentile of the reference
      interval was 18.7 and 17.9 ng/mL for the i1000(SR) and i2000(SR), respectively.
      CONCLUSIONS: The Abbott Galectin-3 assay demonstrated acceptable analytical
      performance on both the ARCHITECT i1000(SR) and ARCHITECT i2000(SR).

PMID- 23010447
TI  - Complement and atherosclerosis-united to the point of no return?
AB  - Atherosclerosis is widely regarded as a chronic inflammatory disease that
      develops as a consequence of entrapment of oxidized low-density lipoprotein (LDL)
      in the arterial intima and its interaction with components of both innate and
      adaptive immunity. This article reviews the role of the complement system in the
      context of a different concept on atherogenesis. Arguments are forwarded in
      support of the contention that enzymatic and not oxidative modification of LDL is
      the prerequisite for transforming the lipoprotein into a moiety that is
      recognized by the innate immune system. In a departure from general wisdom, it is
      proposed that these processes are initially not pathological. To the contrary,
      they are physiological and meaningful because only thus can the stranded
      lipoprotein with its insoluble cargo, cholesterol, be removed from tissues. It is
      contended that histopathologically defined initial foam cell formation develops
      without inflammation and is reversible. Atherosclerosis as a disease evolves only
      when the cholesterol removal machinery is overloaded and it then represents a
      special type of immunopathological process primarily involving immune effectors
      of the innate rather than the adaptive immune system. This sets it apart from
      classical immunopathological reactions that are all based on dysfunctional
      adaptive immunity. But as with all other diseases of known origin, a defined
      molecular trigger, enzymatically modified-LDL (eLDL), exists whose intimal
      accumulation is required to initiate the pathologic process. And as with other
      diseases, the course of atherosclerosis will then be influenced by myriad
      genetic, endogenous, and environmental factors that by themselves, however, will
      not cause the disease. This simple concept is completely in line with general
      clinical experience and with the results of major clinical trials that have been
      conducted during the past decades.

PMID- 23010448
TI  - Clinical and environmental influences on metabolic biomarkers collected for
      newborn screening.
AB  - OBJECTIVES: Identifying common clinical and environmental factors that influence
      newborn metabolic biomarkers will improve the utilization of metabolite panels
      for clinical diagnostic medicine. DESIGN AND METHODS: Environmental effects
      including gender, season of birth, gestational age, birth weight, feeding method
      and age at time of collection were evaluated for over 50 metabolites collected by
      the Iowa Neonatal Metabolic Screening Program on 221,788 newborns over a six year
      period. RESULTS: We replicated well known observations that low birth weight and
      preterm infants have higher essential amino acids and lower medium and long chain
      acylcarnitine levels than their term counterparts. Smaller, but still
      significant, differences were observed for gender and timing of sample
      collection, specifically the season in which the infant was born. Most intriguing
      were our findings of higher thyroid stimulating hormone in the winter months
      (P<1*10(-40)) which correlated with an increased false positive rate of
      congenital hypothyroidism in the winter (0.9%) compared to summer (0.6%).
      Previous studies, conducted globally, have identified an increased prevalence of
      suspected and confirmed cases of congenital hypothyroidism in the winter months.
      We found that the percentage of unresolved suspected cases were slightly higher
      in the winter (0.3% vs. 0.2%). CONCLUSIONS: We identified differences in
      metabolites by gestational age, birth weight, gender and season. Some are widely
      reported such as gestational age and birth weight, while others such as the
      effect of seasonality are not as well studied.

PMID- 23010449
TI  - Low concentration of a Gd-chelate increases the signal-to-noise ratio in fast
      pulsing BEST experiments.
AB  - Despite numerous developments in the past few years that aim to increase the
      sensitivity of NMR multidimensional experiments, NMR spectroscopy still suffers
      from intrinsic low sensitivity. In this report, we show that the combination of
      two developments in the field, the Band-selective Excitation Short-Transient
      (BEST) experiment [Schanda et al., J. Am. Chem. Soc., 128 (2006) 9042] and the
      addition of the nonionic paramagnetic gadolinium chelate gadodiamide into NMR
      samples, enhances the signal-to-noise ratio. This effect is shown here for four
      different proteins, three globular and one unfolded, of molecular weights ranging
      from 6.5 kDa to 40 kDa, using 2D BEST HSQC and 3D BEST triple resonance
      sequences. Moreover, we show that the increase in signal-to-noise ratio provided
      by the gadodiamide is higher for peak resonances with lower than average
      intensity in BEST experiments. It is interesting to note that these residues are
      on average the weakest ones in those experiments. In this case, the gadodiamide
      mediated increase can reach a value of 60% for low and 30% for high molecular
      weight proteins respectively. An investigation into the origin of this
      "paramagnetic gain" in BEST experiments is presented.

PMID- 23010450
TI  - Validation of XiO Electron Monte Carlo-based calculations by measurements in a
      homogeneous phantom and by EGSnrc calculations in a heterogeneous phantom.
AB  - The purpose of the present study is to perform a clinical validation of a new
      commercial Monte Carlo (MC) based treatment planning system (TPS) for electron
      beams, i.e. the XiO 4.60 electron MC (XiO eMC). Firstly, MC models for electron
      beams (4, 8, 12 and 18 MeV) have been simulated using BEAMnrc user code and
      validated by measurements in a homogeneous water phantom. Secondly, these BEAMnrc
      models have been set as the reference tool to evaluate the ability of XiO eMC to
      reproduce dose perturbations in the heterogeneous phantom. In the homogeneous
      phantom calculations, differences between MC computations (BEAMnrc, XiO eMC) and
      measurements are less than 2% in the homogeneous dose regions and less than 1 mm
      shifting in the high dose gradient regions. As for the heterogeneous phantom, the
      accuracy of XiO eMC has been benchmarked with predicted BEAMnrc models. In the
      lung tissue, the overall agreement between the two schemes lies under 2.5% for
      the most tested dose distributions at 8, 12 and 18 MeV and is better than the 4
      MeV one. In the non-lung tissue, a good agreement has been found between BEAMnrc
      simulation and XiO eMC computation for 8, 12 and 18 MeV. Results are worse in the
      case of 4 MeV calculations (discrepancies ~ 4%). XiO eMC can predict dose
      perturbation induced by high-density heterogeneities for 8, 12 and 18 MeV.
      However, significant deviations found in the case of 4 MeV demonstrate that
      caution is necessary in using XiO eMC at lower electron energies.

PMID- 23010451
TI  - Low performance in attention testing is associated with reduced grey matter
      density of the left inferior frontal gyrus in euthyroid patients with Hashimoto's
      thyroiditis.
AB  - Hashimoto's thyroiditis (HT) can casually co-occur with an encephalopathy
      associated with autoimmune thyroid disease. Recently we found an increased
      occurrence of weaknesses in sustained attention and response inhibition in a
      subgroup of euthyroid patients with HT as obtained by the d2 attention test.
      Previous studies in healthy subjects and patients with brain lesions demonstrated
      a pivotal role for the left inferior frontal gyrus (LIFG) in these skills.
      Therefore, we studied the association between the performance in the d2 test and
      grey matter (GM) density of the LIFG in 13 euthyroid patients with HT compared to
      a control group of 12 euthyroid patients with other thyroid diseases. A
      significant correlation between GM density and d2 test total score was detected
      for the opercular part of the LIFG in patients with HT (p<0.001), but not in the
      control group (p=0.94). Regression in patients with HT was significantly stronger
      than in the control group (p=0.02). Moreover, GM density was significantly
      reduced when comparing HT patients with control patients that scored in the lower
      third during d2 attention testing (p<0.05). It can be concluded that in HT
      performance in the d2 test correlated with GM density of the LIFG. Particularly
      low achievement was associated with reduced GM density of this brain region
      suggesting an influence of autoimmune processes on the frontal cortex in this
      disease. This could be due to not yet known antibodies affecting brain morphology
      or an influence of thyroid antibodies themselves.

PMID- 23010453
TI  - A stepforward in understanding the association between social attainment and
      health disparities: evidence from late life telomere length and educational
      level.

PMID- 23010454
TI  - Search for anticonvulsant and analgesic active derivatives of dihydrofuran-2(3H)
      one.
AB  - A series of derivatives of dihydrofuran-2(3H)-one (gamma-butyrolactone, GBL) was
      synthesized and tested for anticonvulsant, neurotoxic and analgesic activity. In
      the anticonvulsant screening 10 lactones were effective in the maximal
      electroshock test (MES) at the highest doses (300 and 100 mg/kg, 0.5 h, ip,
      mice). Statistical analysis showed correlation between the anticonvulsant
      activity and relative lipophilicity parameters determined by experimental and
      computational methods (R(M0), ClogP and MlogP). Preliminary antinociceptive
      evaluation of selected derivatives revealed strong analgesic activity. The
      majority of the tested compounds showed high efficacy in animal models of acute
      pain (hot plate and writhing tests) and strong local anesthetic activity
      (modified tail immersion test). The obtained ED(50) values were comparable with
      such analgesics as acetylsalicylic acid and morphine.

PMID- 23010452
TI  - Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A
      randomized controlled trial.
AB  - Shorter telomeres have been associated with poor health behaviors, age-related
      diseases, and early mortality. Telomere length is regulated by the enzyme
      telomerase, and is linked to exposure to proinflammatory cytokines and oxidative
      stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated
      fatty acid (PUFA) supplementation lowered the concentration of serum
      proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation
      also affected leukocyte telomere length, telomerase, and oxidative stress. In
      addition to testing for group differences, changes in the continuous n-6:n-3 PUFA
      ratio were assessed to account for individual differences in adherence,
      absorption, and metabolism. The double-blind four-month trial included 106
      healthy sedentary overweight middle-aged and older adults who received (1)
      2.5g/day n-3 PUFAs, (2) l.25g/day n-3 PUFAs, or (3) placebo capsules that
      mirrored the proportions of fatty acids in the typical American diet.
      Supplementation significantly lowered oxidative stress as measured by F2
      isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values
      were 15% lower in the two supplemented groups compared to placebo. Although group
      differences for telomerase and telomere length were nonsignificant, changes in
      the n-6:n-3 PUFA plasma ratios helped clarify the intervention's impact: telomere
      length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that
      lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation,
      oxidative stress, and immune cell aging represents important pre-disease
      mechanisms that may be ameliorated through nutritional interventions. This
      translational research broadens our understanding of the potential impact of the
      n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723.

PMID- 23010455
TI  - Synthesis of C-cinnamoyl glycosides and their inhibitory activity against
      mammalian carbonic anhydrases.
AB  - A small series of C-cinnamoyl glycosides incorporating the phenol moiety has been
      prepared by reaction of glycosyl ketones with the appropriate benzaldehydes.
      Glycosides were tested for the inhibition of twelve mammalian isoforms of
      carbonic anhydrase. This is the first study in which alpha-CAs have been
      investigated for their interaction with C-glycosides, a novel carbohydrate
      scaffold in the design of carbonic anhydrase inhibitors. The C-cinnamoyl
      glycosides were generally effective CA inhibitors, with inhibition constants in
      the low micromolar range against CA I, II, IV, VA, VB, VI, VII, IX, XII, XIII,
      XIV and ineffective inhibitors of CA III. These results confirm that attaching
      carbohydrate moieties to CA phenol pharmacophore improves its inhibitory
      activity.

PMID- 23010456
TI  - Synthesis and structure-activity relationship of fused-pyrimidine derivatives as
      a series of novel GPR119 agonists.
AB  - A series of fused-pyrimidine derivatives have been discovered as potent and
      orally active GPR119 agonists. A combination of the fused-pyrimidine structure
      and 4-chloro-2,5-difluorophenyl group provided the 5,7-dihydrothieno[3,4
      d]pyrimidine 6,6-dioxide derivative 14a as a highly potent GPR119 agonist.
      Further optimization of the amino group at the 4-position in the pyrimidine ring
      led to the identification of 2-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxido
      5,7-dihydrothieno[3,4-d]pyrimidin-4-yl]piperidin-4-yl}acetamide (16b) as an
      advanced analog. Compound 16b was found to have extremely potent agonistic
      activity and improved glucose tolerance at 0.1 mg/kg po in mice. We consider
      compound 16b and its analogs to have clear utility in exploring the practicality
      of GPR119 agonists as potential therapeutic agents for the treatment of type 2
      diabetes mellitus.

PMID- 23010457
TI  - Ibuprofen-loaded chitosan and chemically modified chitosans--release features
      from tablet and film forms.
AB  - The biopolymer chitosan was chemically modified in two sequences of reactions:
      (i) immobilization of methyl acrylate followed by cysteamine and (ii) the
      sequence of immobilization reactions involving ethylene sulfide, methyl acrylate
      and finally cysteamine. In both cases the pendant chains have attached nitrogen,
      oxygen and sulfur basic centers. The corresponding structures were characterized
      through elemental analysis, infrared spectroscopy, nuclear magnetic resonance in
      the solid state for carbon, thermogravimetry and scanning electron microscopy.
      The newly synthesized biopolymers have abilities to immobilize and controllably
      release the non-steroidal drug ibuprofen. The ibuprofen-loaded biomaterials as
      tablets or as films crosslinked with glutaraldehyde revealed that drug release is
      pH sensitive. The chemically modified chitosan may allow reduction of drug
      release in stomach fluids, since the functional groups cause a decrease in
      swelling rate at pH 1.2, opposite to the behavior that occurs at pH 7.4, that of
      nutritional fluid, where an increase of the rate of swelling occurs. In such
      conditions the negatively charge ibuprofen is electrostatically repelled by
      negative chitosan derivative surfaces.

PMID- 23010458
TI  - Prenatal ultrasound diagnosis of holoprosencephaly and associated anomalies.
AB  - Holoprosencephaly is a rare spectrum of cerebral and facial malformations
      resulting from incomplete division of the embryonic forebrain (prosencephalon)
      into distinct lateral cerebral hemisphere. Holoprosencephaly spectrum in the
      fetus is often associated with other anomalies, particularly of the face and
      extremities. Here we present three different cases of patients with
      holoprosencephaly who failed to attain routine sonography during 11-20 weeks
      owing to some unavoidable circumstances. Two of them were diagnosed during the
      third trimester and one in the late second trimester. Ultrasound findings of
      associated anomalies were confirmed after a clinical examination of the delivered
      fetuses.

PMID- 23010459
TI  - Successful management of congenital chylous ascites with early octreotide and
      total parenteral nutrition in a newborn.
AB  - Congenital chylous ascites (CCA) is a rare disease that results from
      maldevelopment of the intra-abdominal lymphatic system. Few cases have been
      described and no gold standard treatment has been defined so far. Octreotide, a
      somatostatin analogue, has been used for the treatment of CCA, but always after a
      failed conservative approach with fasting, total parenteral nutrition (TPN) or
      medium chain triglyceride (MCT) feeds. We report the case of a newborn with CCA
      treated by fasting, TPN and octreotide for a period of 15 days until the
      abdominal distension was successfully reduced at which point treatment was
      switched to an MCT formula. On day 25 the patient was breastfed and was
      discharged on day 33. No recurrence of chylous ascites was noted. Our experience
      highlights the successful treatment with TPN and octreotide as the first step for
      the conservative approach of CCA in a newborn, reducing the length of treatment
      and hospitalisation.

PMID- 23010460
TI  - Penoscrotal entrapment: a safe, innovative technique for removing metal
      constricting devices.
AB  - Penoscrotal entrapment is a rare urological emergency that requires urgent
      treatment to avoid penile ischaemia and subsequent erectile dysfunction. Non
      metallic and thin metallic objects are easily removed via cutting, while thick
      metallic constricting devices require specialist saws or motorised cutters, all
      of which may be difficult to locate in the emergency setting. We report a case of
      a 45-year-old patient who presented with a 48-h history of gross penoscrotal
      oedema secondary to entrapment by a thick metal ring (internal diameter 55 mm,
      external diameter 74 mm and thickness 19 mm). The positioning, thickness of the
      ring, delayed presentation and extensive oedema meant its removal was especially
      challenging. We improvised a simple, three-step technique (aspiration, strapping
      and sling) which enabled the metal ring to be removed without the need for
      specialist equipment. We would encourage others to employ this safe technique in
      an emergency setting.

PMID- 23010461
TI  - Recurrent hyperphosphatemic tumoural calcinosis.
AB  - Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur
      in a variety of clinical settings, characterised by subcutaneous deposition of
      calcium phosphate with or without giant cell reaction. We describe a case of 11
      year-old girl presenting with recurrent hard swellings in the vicinity of
      shoulder and hip joints associated with elevated serum phosphate and normal serum
      calcium levels. TC has been mainly reported from Africa, with very few cases
      reported from India. After the diagnosis of hyperphosphatemic TC was established,
      the patient was treated with oral sevelamer and is under constant follow-up to
      detect recurrence, if any. The present case highlights the fact that although an
      uncommon lesion, TC must be considered in the differential diagnosis of
      subcutaneous hard lump in the vicinity of a joint.

PMID- 23010462
TI  - Recurrence of a paediatric arteriovenous malformation 9 years postcomplete
      excision: case report and review of literature.
AB  - Cerebral arteriovenous malformations (AVMs) are a common congenital vascular
      anomaly, which often present in both children and adults. Surgery is considered
      curative once postoperative angiography confirms the absence of vessels. We
      describe a 6-year-old girl, who had a Spetzler-Martin Grade II AVM resected
      successfully, in which a recurrent AVM was detected on routine follow-up over 9
      years post excision. The aetiopathogenesis of this rare occurrence with a review
      of literature is discussed. Long-term postoperative follow-up in the form of
      MRI/MR angiogram is recommended for all fully resected AVMs in the paediatric age
      group, anticipating the possibility of future recurrence.

PMID- 23010463
TI  - Extensive extracranial and intracranial Varicella zoster vasculopathy.
AB  - Varicella zoster virus (VZV)-induced vasculopathy is an uncommon cause of stroke
      in a young immunocompetent host. Owing to scarcity of data of VZV-induced
      vasculopathy and lack of awareness about this condition and its diagnostic test,
      these cases may be easily missed. In this case, we report an immunocompetent host
      presenting right-side hemiplegia with motor aphasia and complete loss of vision
      in the left eye due to complete occlusion of the left common carotid artery
      without any history of skin rash preceding stroke. Cerebrospinal fluid analysis
      for varicella antibody revealed very high titres and CT aortogram demonstrated
      aortoarteritis with occlusion of left common carotid artery. To our knowledge,
      varicella zoster vasculopathy-associated aortoarteritis has not been described in
      the literature.

PMID- 23010464
TI  - Giant cavernous carotid artery aneurysm mimicking a fungal granuloma and
      presenting with massive epistaxis.
AB  - A 42-year-old man presented with frequent minor nasal bleeds since 1 month. He
      was undergoing chemotherapy for pulmonary tuberculosis. MRI brain revealed a
      space occupying lesion in the right cavernous sinus extending to sphenoid sinus,
      with T2 inversion. An initial diagnosis of fungal granuloma was made and
      endoscopic trans-nasal biopsy was attempted. During surgery, a pink pulsating
      mass was seen in the sphenoid sinus and the procedure was abandoned. A cerebral
      CT-angiography done subsequently revealed a giant right cavernous segment
      internal carotid artery (ICA) aneurysm. He was then referred to our centre and
      upon admission he collapsed secondary to a major bout of epistaxis. An emergency
      cervical carotid artery ligation resulted in transient control of epistaxis.
      Owing to recurrence of bleed, trapping of the aneurysm was done resulting in
      cure. The present case shows that a giant cavernous ICA aneurysm can occasionally
      be erroneously diagnosed as fungal granuloma.

PMID- 23010465
TI  - Postchemotherapy expulsion of oesophageal endoluminal stent with vomiting: a rare
      occurrence.
AB  - Self-expandable metallic stents (SEMS) are currently the most widely used
      modality for palliation of dysphagia from oesophageal malignancy. However,
      placement of SEMS is associated with a number of complications. We report a rare
      late complication of SEMS placed for relief of malignant dysphagia (Locally
      advanced Carcinoma mid-esophagus) in a 65-year-old man. SEMS was expelled out
      intact with vomiting following complete response to disease after three cycles of
      chemotherapy. Check on endoscopy done the day after, patient's growth had shown
      partial response to chemotherapy with scope easily negotiable upto
      Gastroesophageal junction with area of scarring and healed ulceration and stent
      imprint on the oesophageal wall. Partial response of the disease to chemotherapy
      and lack of expected fibrosis between stent and oesophageal wall resulted in loss
      of scaffolding for the stent and its subsequent expulsion in vomiting and relief
      in patient's dysphagia.

PMID- 23010466
TI  - Acute tuberculous abscess of the thyroid gland.
AB  - The authors are presenting our experience of managing an interesting case of a 28
      year-old woman who presented to our clinic with a midline neck swelling of 1
      month duration. There was a rapid increase in the degree of swelling associated
      with erythema, pain and fever 7 days before seeking medical help. Plain and
      contrast-enhanced CT scans of the neck were done. Diagnosis of acute suppurative
      abscess was made and the patient underwent emergency incision and drainage.
      Histopathological examination of the abscess wall showed epitheloid and Langhans'
      giant cells. The findings were suggestive of tuberculosis. Subsequently, a
      positive culture for Mycobacterium tuberculosis was obtained on Lowenstein-Jenson
      medium. The patient was started on antituberculous chemotherapy for 6 months. On
      a 6-month clinical follow-up, the patient was asymptomatic and euthyroid. We
      discuss the clinical presentation, diagnosis and treatment of this case as well
      as a review of the literature.

PMID- 23010467
TI  - Appendiceal torsion associated with undescended caecum: a case report and review
      of the literature.
AB  - Torsion of the vermiform appendix is a rare disorder that causes symptoms similar
      to those of acute appendicitis. Primary and secondary causes of appendiceal
      torsion have been reported in the literature. Laparoscopy appears to be the most
      appropriate modality for diagnosis and treatment where the condition is
      suspected. To our knowledge this is the first case of appendiceal torsion in an
      adult causing right upper quadrant pain related to caecal malposition.

PMID- 23010468
TI  - Repeated exposure to codeine alters morphine glucuronidation by affecting UGT
      gene expression in the rat.
AB  - We have previously found that phenantrenic opioids, such as heroin or naltrexone,
      modulate morphine glucuronidation in the rat. Here we further investigated the
      effects of phenantrenic opioids on morphine glucuronidation comparing the effects
      of codeine and heroin. In particular, we measured the synthesis of morphine-3
      glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine: in the liver
      microsomal preparations obtained from rats repeatedly treated with two different
      doses of codeine (ex vivo study); in primary cultures of rat hepatocytes
      previously incubated for 72h with codeine, or heroin (in vitro study); in the
      latter conditions, the levels of expression of genes coding for uridine-5'
      diphosphate-glucuronosyltransferases (UGTs) A1, A6, A7 and 2B1 were also
      determined; finally, the levels of glucuronic acid in rat hepatocytes previously
      incubated for 72h with codeine or heroin were assessed. The ex vivo study shows
      that codeine exposure in vivo stimulated liver microsomal M3G formation and de
      novo synthesis of M6G. Differently, in primary hepatocyte cultures both codeine
      and heroin inhibited M3G formation, whereas heroin only stimulated de novo
      synthesis of M6G; moreover, codeine significantly reduced UGT2B1 expression at 6h
      and caused a trend toward inhibition of UGT1A1 expression at 72h; heroin enhanced
      UGT2B1 expression and inhibited that of UGT1A1 at 72h; finally, both codeine and
      heroin depleted UDPGA content of hepatocytes. In conclusion, codeine affects
      liver glucuronidation of morphine enlightening the possible contribution of
      changes in the spectrum of UGT gene expression and co-factor synthesis in this
      phenomenon.

PMID- 23010469
TI  - The triple reuptake inhibitor DOV 216,303 induces long-lasting enhancement of
      brain reward activity as measured by intracranial self-stimulation in rats.
AB  - Triple reuptake inhibitors (TRIs) are potential new antidepressants, which not
      only enhance brain serotonin and norepinephrine concentrations but also increase
      dopamine levels. Therefore TRIs are believed to have faster therapeutic onset
      than SSRIs, and may be particularly useful for the treatment of anhedonia (i.e.
      inability to experience pleasure), one of the core symptoms of major depression.
      The current study aimed at getting better insight into the rewarding properties
      of DOV 216,303, which is a TRI, regarding its possible use to treat anhedonia. It
      is known that psychostimulant drugs lower intracranial self-stimulation (ICSS)
      reward thresholds, reflecting enhanced brain reward activity, whereas withdrawal
      from those compounds mostly results in increased ICSS thresholds. Therefore we
      assessed the effects of DOV 216,303 on ICSS thresholds in rats. Animals were
      trained in the discrete-trial current-threshold procedure and after stable ICSS
      reward thresholds were established, animals received one injection per day of DOV
      216,303 (20mg/kg) or amphetamine (5mg/kg) for four consecutive days. ICSS
      thresholds were assessed 3, 6, and 23 h after each injection. DOV 216,303
      decreased ICSS thresholds up to 6h after drug treatment. To our knowledge this is
      the first time that a triple reuptake inhibitor, DOV 216,303, induces relatively
      long-lasting enhancement of brain reward activity. Elevated ICSS thresholds were
      found after amphetamine administration, which is consistent with previously
      reported reward deficits induced after amphetamine-withdrawal.

PMID- 23010470
TI  - The cross talk between pathways in the repair of 8-oxo-7,8-dihydroguanine in
      mouse and human cells.
AB  - Although oxidatively damaged DNA is repaired primarily via the base excision
      repair (BER) pathway, it is now evident that multiple subpathways are needed.
      Yet, their relative contributions and coordination are still unclear. Here, mouse
      embryo fibroblasts (MEFs) from selected nucleotide excision repair (NER) and/or
      BER mouse mutants with severe (Csb(m/m)/Xpa(-/-) and Csb(m/m)/Xpc(-/-)), mild
      (Csb(m/m)), or no progeria (Xpa(-/-), Xpc(-/-), Ogg1(-/-), Csb(m/m)/Ogg1(-/-)) or
      wild-type phenotype were exposed to an oxidizing agent, potassium bromate, and
      genomic 8-oxo-7,8-dihydroguanine (8-oxoGua) levels were measured by HPLC-ED. The
      same oxidized DNA base was measured in NER/BER-defective human cell lines
      obtained after transfection with replicative plasmids encoding siRNA targeting
      DNA repair genes. We show that both BER and NER factors contribute to the repair
      of 8-oxoGua, although to different extents, and that the repair profiles are
      similar in human compared to mouse cells. The BER DNA glycosylase OGG1 dominates
      8-oxoGua repair, whereas NER (XPC, XPA) and transcription-coupled repair proteins
      (CSB and CSA) are similar, but minor contributors. The comparison of DNA
      oxidation levels in double versus single defective MEFs indicates increased
      oxidatively damaged DNA only when both CSB and XPC/XPA are defective, indicating
      that these proteins operate in different pathways. Moreover, we provide the first
      evidence of an involvement of XPA in the control of oxidatively damaged DNA in
      human primary cells.

PMID- 23010471
TI  - Therapeutic approach to patients with familial Mediterranean fever-related
      amyloidosis resistant to colchicine.
AB  - The frequency of FMF-related amyloidosis has been decreased by colchicine use
      over the past few decades. However, the beneficial effect of colchicine may
      differ in accordance with nephropathic stages. When used in proper doses and with
      compliance, colchicine is very effective in preclinical and proteinuric stages of
      FMF-related amyloidosis. Even so, a large number of patients with nephrotic range
      proteinuria, despite compliance and an ideal dose of colchicine, may still
      progress to end-stage renal failure (ESRF).We do not know exactly what we can do
      with such patients. This paper discusses the therapeutic approach to patients
      with FMF-related amyloidosis.

PMID- 23010472
TI  - NPC1 defect results in abnormal platelet formation and function: studies in
      Niemann-Pick disease type C1 patients and zebrafish.
AB  - Niemann-Pick type C is a lysosomal storage disease associated with mutations in
      NPC1 or NPC2, resulting in an accumulation of cholesterol in the endosomal
      lysosomal system. Niemann-Pick type C has a clinical spectrum that ranges from a
      neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative
      disease combined with remarkably, in some cases, hematological defects such as
      thrombocytopenia, anemia and petechial rash. A role of NPC1 in hematopoiesis was
      never shown. Here, we describe platelet function abnormalities in three unrelated
      patients with a proven genetic and biochemical NPC1 defect. Their platelets have
      reduced aggregations, P-selectin expression and ATP secretions that are
      compatible with the observed abnormal alpha and reduced dense granules as studied
      by electron microscopy and CD63 staining after platelet spreading. Their blood
      counts were normal. NPC1 expression was shown in platelets and megakaryocytes
      (MKs). In vitro differentiated MKs from NPC1 patients exhibit hyperproliferation
      of immature MKs with different CD63(+) granules and abnormal cellular
      accumulation of cholesterol as shown by filipin stainings. The role of NPC1 in
      megakaryopoiesis was further studied using zebrafish with GFP-labeled
      thrombocytes or DsRed-labeled erythrocytes. NPC1 depletion in zebrafish resulted
      in increased cell death in the brain and abnormal cellular accumulation of
      filipin. NPC1-depleted embryos presented with thrombocytopenia and mild anemia as
      studied by flow cytometry and real-time QPCR for specific blood cell markers. In
      conclusion, this is the first report, showing a role of NPC1 in platelet function
      and formation but further studies are needed to define how cholesterol storage
      interferes with these processes.

PMID- 23010473
TI  - Integrative genomics reveals frequent somatic NF1 mutations in sporadic
      pheochromocytomas.
AB  - Pheochromocytomas are neuroendocrine tumors of the adrenal medulla which can
      occur either sporadically or in the context of hereditary tumor syndromes.
      Whereas the genetic background of hereditary pheochromocytomas is becoming rather
      well-defined, very little is known about the more common sporadic form of the
      disease which constitutes ~70% of all cases. In this study, we elucidate some of
      the molecular mechanisms behind sporadic pheochromocytoma by performing a
      comprehensive analysis of copy number alterations, gene expression, promoter
      methylation and somatic mutations in the genes RET, VHL, NF1, SDHA, SDHB, SDHC,
      SDHD, SDHAF2, KIF1Bbeta, TMEM127 and MAX, which have been associated with
      hereditary pheochromocytoma or paraganglioma. Our genomic and genetic analyses of
      42 sporadic pheochromocytomas reveal that a large proportion (83%) has an altered
      copy number in at least one of the known susceptibility genes, often in
      association with an altered messenger RNA (mRNA) expression. Specifically, 11
      sporadic tumors (26%) displayed a loss of one allele of the NF1 gene, which
      significantly correlated with a reduced NF1 mRNA expression. Subsequent
      sequencing of NF1 mRNA, followed by confirmation in the corresponding genomic DNA
      (gDNA), revealed somatic truncating mutations in 10 of the 11 tumors with NF1
      loss. Our results thus suggest that the NF1 gene constitutes the most frequent
      (24%) target of somatic mutations so far known in sporadic pheochromocytomas.

PMID- 23010474
TI  - New trends in lysophospholipid research.

PMID- 23010475
TI  - Cholesterol efflux is differentially regulated in neurons and astrocytes:
      implications for brain cholesterol homeostasis.
AB  - Disruption of cholesterol homeostasis in the central nervous system (CNS) has
      been associated with neurological, neurodegenerative, and neurodevelopmental
      disorders. The CNS is a closed system with regard to cholesterol homeostasis, as
      cholesterol-delivering lipoproteins from the periphery cannot pass the blood
      brain-barrier and enter the brain. Different cell types in the brain have
      different functions in the regulation of cholesterol homeostasis, with astrocytes
      producing and releasing apolipoprotein E and lipoproteins, and neurons
      metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that
      astrocytes and neurons adopt different mechanisms also in regulating cholesterol
      efflux. We found that in astrocytes cholesterol efflux is induced by both lipid
      free apolipoproteins and lipoproteins, while cholesterol removal from neurons is
      triggered only by lipoproteins. The main pathway by which apolipoproteins induce
      cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by
      inhibiting its activity and silencing its expression, we show that ABCA1 is
      involved in cholesterol efflux from astrocytes but not from neurons. Furthermore,
      our results suggest that ABCG1 is involved in cholesterol efflux to
      apolipoproteins and lipoproteins from astrocytes but not from neurons, while
      ABCG4, whose expression is much higher in neurons than astrocytes, is involved in
      cholesterol efflux from neurons but not astrocytes. These results indicate that
      different mechanisms regulate cholesterol efflux from neurons and astrocytes,
      reflecting the different roles that these cell types play in brain cholesterol
      homeostasis. These results are important in understanding cellular targets of
      therapeutic drugs under development for the treatments of conditions associated
      with altered cholesterol homeostasis in the CNS.

PMID- 23010476
TI  - The ins and outs of phosphatidylethanolamine synthesis in Trypanosoma brucei.
AB  - Phospholipids are not only major building blocks of biological membranes but
      fulfill a wide range of critical functions that are often widely unrecognized. In
      this review, we focus on phosphatidylethanolamine, a major glycerophospholipid
      class in eukaryotes and bacteria, which is involved in many unexpected biological
      processes. We describe (i) the ins, i.e. the substrate sources and biochemical
      reactions involved in phosphatidylethanolamine synthesis, and (ii) the outs, i.e.
      the different roles of phosphatidylethanolamine and its involvement in various
      cellular events. We discuss how the protozoan parasite, Trypanosoma brucei, has
      contributed and may contribute in the future as eukaryotic model organism to our
      understanding of phosphatidylethanolamine homeostasis. This article is part of a
      Special Issue entitled Phospholipids and Phospholipid Metabolism.

PMID- 23010480
TI  - Determination of andrograpolide sodium bisulphite in Beagle dog plasma by LC
      MS/MS and its application to pharmacokinetics.
AB  - A sensitive and reliable liquid chromatography-tandem mass spectrometry (LC
      MS/MS) has been developed and validated for the determination of andrographolide
      sodium bisulphite (ASB) in dog plasma using dehydroandrographolide (DAG) as an
      internal standard. Chromatographic separation was achieved on a Hypersil Gold
      C(18) column (50 mm * 2.1 mm, 1.9 MUm) with gradient elution that consisted of
      methanol and water at a flow rate of 0.2 mL/min. Quantification was done using
      selected reaction monitoring (SRM) mode to monitor precursor-product ion
      transitions of m/z 413.2->287.2 for ASB and 331.2->303.3 for DAG at negative
      ionization mode. Good linearity was obtained over the range of 10-1000 ng/mL and
      the correlation coefficient was better than 0.99. The intra- and inter-day
      accuracies ranged from 97.2% to 107.8% and precisions (RSD) were within 13.9%.
      ASB was found stable under three freeze-thaw cycles, short-term temperature, post
      preparative and long-term temperature conditions. The method was successfully
      applied to a pharmacokinetic study of ASB intravenously administered to Beagle
      dogs.

PMID- 23010479
TI  - Analysis of daidzein in nanoparticles after oral co-administration with sodium
      caprate to rats by ultra-performance liquid chromatography-quadrupole-time-of
      flight mass spectrometry.
AB  - An ultra-performance-liquid-chromatography-quadrupole-time-of-flight mass
      spectrometry (UPLC/Q-TOF-MS) method was developed and validated for the
      quantitation of daidzein (DZ) in rat plasma. Ethylparaben was chosen as internal
      standards (IS). DZ was linear over the range of 0.001-5 MUg/mL. The lower limit
      of quantification (LLOQ) was 0.001 MUg/mL and the limit of detection (LOD) was
      0.0005 MUg/mL. The intra-day and inter-day relative standard deviations (RSDs)
      were ranged from 3.59% to 6.43% and 5.35% to 7.25%, respectively. This UPLC/Q-TOF
      MS method provided good specifity, highly sensitivity, accurate and high-speed
      detection (6 min), applicable to the pharmacokinetics study in rats in vivo after
      oral administration of free daidzein solution, daidzein-loaded poly (lactide-co
      glycolide) (PLGA) nanoparticles (D-NPs) suspension and D-NPs co-administered with
      sodium caprate (C(10)) which as the oral absorption promoter. It was shown that
      the pharmacokinetics behavior was significantly improved after the oral
      administration of D-NPs suspension co-administered with absorption promoter C(10)
      by the fact that the relative bioavailability were enhanced about 4.24-fold,
      compared to that of DZ suspension.

PMID- 23010478
TI  - Cardiac progenitor cells engineered with Pim-1 (CPCeP) develop cardiac phenotypic
      electrophysiological properties as they are co-cultured with neonatal myocytes.
AB  - Stem cell transplantation has been successfully used for amelioration of
      cardiomyopathic injury using adult cardiac progenitor cells (CPC). Engineering of
      mouse CPC with the human serine/threonine kinase Pim-1 (CPCeP) enhances
      regeneration and cell survival in vivo, but it is unknown if such apparent
      lineage commitment is associated with maturation of electrophysiological
      properties and excitation-contraction coupling. This study aims to determine
      electrophysiology and Ca(2+)-handling properties of CPCeP using neonatal rat
      cardiomyocyte (NRCM) co-culture to promote cardiomyocyte lineage commitment.
      Measurements of membrane capacitance, dye transfer, expression of connexin 43
      (Cx43), and transmission of ionic currents (I(Ca), I(Na)) from one cell to the
      next suggest that a subset of co-cultured CPCeP and NRCM becomes connected via
      gap junctions. Unlike NRCM, CPCeP had no significant I(Na), but expressed
      nifedipine-sensitive I(Ca) that could be measured more consistently with Ba(2+)
      as permeant ion using ramp-clamp protocols than with Ca(2+) and step
      depolarization protocols. The magnitude of I(Ca) in CPCeP increased during
      culture (4-7 days vs. 1-3 days) and was larger in co-cultures with NRCM and with
      NRCM-conditioned medium, than in mono-cultured CPCeP. I(Ca) was virtually absent
      in CPC without engineered expression of Pim-1. Caffeine and KCl-activated Ca(2+)
      transients were significantly present in co-cultured CPCeP, but smaller than in
      NRCM. Conversely, ATP-induced (IP(3)-mediated) Ca(2+) transients were larger in
      CPCeP than in NRCM. I(NCX) and I(ATP) were expressed in equivalent densities in
      CPCeP and NRCM. These in vitro studies suggest that CPCeP in co-culture with
      NRCM: a) develop I(Ca) current and Ca(2+) signaling consistent with cardiac
      lineage, b) form electrical connections via Cx43 gap junctions, and c) respond to
      paracrine signals from NRCM. These properties may be essential for durable and
      functional myocardial regeneration under in vivo conditions.

PMID- 23010477
TI  - Phosphatidylcholine and the CDP-choline cycle.
AB  - The CDP-choline pathway of phosphatidylcholine (PtdCho) biosynthesis was first
      described more than 50 years ago. Investigation of the CDP-choline pathway in
      yeast provides a basis for understanding the CDP-choline pathway in mammals.
      PtdCho is considered as an intermediate in a cycle of synthesis and degradation,
      and the activity of a CDP-choline cycle is linked to subcellular membrane lipid
      movement. The components of the mammalian CDP-choline pathway include choline
      transport, choline kinase, phosphocholine cytidylyltransferase, and choline
      phosphotransferase activities. The protein isoforms and biochemical mechanisms of
      regulation of the pathway enzymes are related to their cell- and tissue-specific
      functions. Regulated PtdCho turnover mediated by phospholipases or neuropathy
      target esterase participates in the mammalian CDP-choline cycle. Knockout mouse
      models define the biological functions of the CDP-choline cycle in mammalian
      cells and tissues. This article is part of a Special Issue entitled Phospholipids
      and Phospholipid Metabolism.

PMID- 23010482
TI  - Dasatinib, a multi-kinase inhibitor increased radiation sensitivity by
      interfering with nuclear localization of epidermal growth factor receptor and by
      blocking DNA repair pathways.
AB  - BACKGROUND AND PURPOSE: Although inhibition of epidermal growth factor receptor
      (EGFR) signaling during radiation led to improvement of tumor control and
      survival, novel strategies are needed to further improve the outcome of patients
      with locally advanced head and neck carcinoma. Because EGFR is known to interact
      with c-Src kinases, the present study investigated dasatinib (BMS-354825), an
      inhibitor of c-Src kinases, for its efficacy in enhancing radiosensitivity of
      human head and neck squamous cell carcinomas (HNSCC) in vitro and examined the
      underlying mechanisms for this effect. MATERIALS AND METHODS: Six HNSCC lines
      were exposed to dasatinib, radiation, or both, and assessed for c-Src and EGFR
      expression, cell survival and colony forming ability. Among these cell lines, HN
      5 and FaDu lines were analyzed for induction of apoptosis, cell cycle re
      distribution and for nuclear localization of EGFR, gamma-H2AX and 53BP1 proteins.
      Immuno-precipitation and Western blots were performed to analyze the levels and
      binding of proteins involved in cell survival, apoptosis and DNA repair pathways.
      Suppression of c-Src by siRNA and subsequent clonogenic assay was performed in HN
      5 cells. RESULTS: All six HNSCC lines that were examined expressed high levels of
      c-Src. Two (HN-5 and MDA-183) expressed higher levels of EGFR than other lines.
      Dasatinib suppressed cell survival of all cell lines tested independent of c-Src
      or EGFR levels but enhanced the radiosensitivity of HN-5 and MDA-183. HN-5 and
      FaDu were analyzed further. Dasatinib suppressed phosphorylation of c-Src in both
      cell lines, but decreased repair of radiation-induced DNA damage in HN-5 cells
      only as evidenced by suppression of c-Abl and Nbs-1 activity, inhibition of the
      association between c-Src and EGFR or Her-2, prolongation of nuclear gamma-H2AX
      and 53BP1 foci and inhibition of EGFR nuclear localization and its association
      with DNA-PKcs. Finally, partial suppression of c-Src resulted in a small increase
      in HN-5 cell radiosensitivity. CONCLUSIONS: Our data demonstrate that dasatinib
      induces apoptosis and blocks DNA repair in EGFR-expressing HNSCC cells and
      improves radiotherapy outcome. These findings warrant further investigation using
      in vivo tumor models for potential translation into clinical testing.

PMID- 23010483
TI  - Effect of freezing-thawing process and quercetin on human sperm survival and DNA
      integrity.
AB  - We aimed in the first part of our work to study the effect of cryopreservation on
      the human sperm DNA integrity and the activation of caspase 3, the main apoptosis
      indicator. In the second part, we were interested in testing the effect of
      quercetin, as an antioxidant, in preventing sperm damage during the freeze
      thawing process. Seventeen semen samples were obtained from 17 men recruited for
      infertility investigations. Liquefied sperm was cryopreserved using
      spermfreeze(r). Nine of the used samples were divided into two aliquots; the
      first one was cryopreserved with spermfreeze only (control) and the second one
      was cryopreserved with spermfreeze supplemented with quercetin to a final
      concentration of 50 MUM. Sperm motility and viability were assessed according to
      WHO criteria. We used TUNEL assay and the Oxy DNA assay to assess sperm DNA
      integrity. Activated caspase 3 levels were measured in spermatozoa using
      fluorescein-labeled inhibitor of caspase (FLICA). Cryopreservation led to a
      significant increase in sperm DNA fragmentation, DNA oxidation and caspase 3
      activation (p<0.01). Supplementation of the cryopreservation medium with
      quercetrin induced a significant improvement in post thaw sperm parameters,
      compared to those of control, regarding sperm motility (p=0.007), viability
      (p=0.008) and DNA integrity (p=0.02); however, it had no effect on caspase 3
      activation (p=0.3). We conclude that oxidative stress plays a major role in
      inducing sperm cryodamage but implication of apoptosis in this impairment
      requires further investigations. Quercetin could have protective effect during
      cryopreservation but further research is needed to confirm this effect.

PMID- 23010484
TI  - Methionine supplementation improves ram sperm parameters during liquid storage at
      5 degrees C.
AB  - The aim of this study was to investigate the effects of methionine and lipoic
      acid on ram sperm parameters during liquid storage (5  degrees C). Ejaculates
      collected from five Merino rams were pooled at 37  degrees C. Each pooled
      ejaculate was divided into five equal aliquots and diluted (37  degrees C) with
      five extenders, one of which was without additives, two of which contained
      methionine at two different doses, and the other two of which contained lipoic
      acid at two different doses. Sperm parameters were determined at 0, 24, 48, 72
      and 96 h of liquid storage at 5  degrees C. The extenders containing 2 and 4mM of
      methionine resulted in higher motility percentages, in comparison to the control,
      up to 96 h of storage. Methionine at doses of 2 and 4mM led to higher viability
      and sperm mitochondrial activity percentages, when compared to the controls
      during 48, 72 and 96 h of liquid storage (P<0.05). The findings of this study
      showed that methionine was of greater benefit to ram sperm parameters during
      liquid storage.

PMID- 23010485
TI  - Multivariate prediction of emerging psychosis in adolescents at high risk for
      schizophrenia.
AB  - BACKGROUND: Accurate prediction of psychosis development in high-risk populations
      is an important but thus far elusive goal. Of the many diverse etiologic and risk
      factors identified thus far, few have been combined into prospective multivariate
      risk ascertainment models. We tested the predictive power of familial,
      neurobiological, socioenvironmental, cognitive and clinical risk factors through
      an integrative biopsychosocial model for emerging psychosis in young relatives at
      familial risk for schizophrenia. METHODS: 96 young first- and second- degree
      relatives of schizophrenia probands were followed for an average of 2.38
      (SD=0.98) years to examine their trajectory towards psychosis. Iterative
      structural equation modelling utilizing multiple etiologic and risk factors was
      employed to estimate their joint contribution to prediction of psychosis
      development. RESULTS: The rate of conversion to psychosis over the study period
      was 12.5%. In the final model, clinical measures of schizotypy were directly
      predictive of conversion, with early (familial, biological, socioenvironmental)
      and cognitive risk factors indirectly predictive of psychosis through increased
      baseline clinical symptomatology. Our model provided an excellent fit to the
      observed data, with sensitivity of 0.17, specificity of 0.99, positive predictive
      value of 0.67 and negative predictive value of 0.89. CONCLUSIONS: Integrative
      modeling of multivariate data from familial, neurobiological, socioenvironmental,
      cognitive and clinical domains represents a powerful approach to prediction of
      psychosis development. The high specificity and low sensitivity found using a
      combination of such variables suggests that their utility may be in confirmatory
      testing among already selected high-risk individuals, rather than for initial
      screening. These findings also highlight the importance of data from a broad
      array of etiologic and risk factors, even within a familial high-risk population.
      With further refinement and validation, such methods could form key components of
      early detection, intervention and prevention programs.

PMID- 23010486
TI  - Expression analysis of a novel mRNA variant of the schizophrenia risk gene
      ZNF804A.

PMID- 23010487
TI  - The denial of aggression in violent patients with schizophrenia.
AB  - BACKGROUND: There is no literature investigating denial of aggression in
      schizophrenia. Our goal was to study this phenomenon and to determine what
      deficits are associated with it. METHODS: 102 inpatients with schizophrenia were
      divided into three groups: (1) patients with a documented history of violent
      crime who denied it on extensive interviews ("deniers"); (2) those with such a
      history who admitted to it; and (3) those without violent crime. Patients were
      administered a psychometrically validated self-report scale of aggression, the
      Buss-Perry Aggression Questionnaire (BPAQ), the Positive and Negative Syndrome
      Scale and a comprehensive neurocognitive battery. They were followed for twelve
      weeks during which all violent incidents were recorded. RESULTS: The deniers were
      significantly more impaired in executive function, but not in any other cognitive
      domain. They did not evidence more severe psychotic symptoms or greater lack of
      insight in their psychosis, but this lack of insight was strongly related to
      hostility and suspiciousness. Their denial of aggression was also evidenced in a
      significantly lower self-reported BPAQ aggression score. In the patients who
      admitted to violent crimes, baseline BPAQ aggression score predicted subsequent
      aggression; in the deniers, it was negatively related to subsequent aggression.
      CONCLUSION: Denial of aggression is associated with executive dysfunction which
      facilitates a misappraisal of the surrounding world as threatening and hostile.
      For those who admit to crimes, self-reported aggression predicts future
      aggression. In contrast, in the deniers, the extent of denial is related to
      future aggression. The denial itself is a marker of greater aggressive
      tendencies.

PMID- 23010488
TI  - Rapid clozapine dose titration and concomitant sodium valproate increase the risk
      of myocarditis with clozapine: a case-control study.
AB  - BACKGROUND: Despite the implementation of cardiac monitoring guidelines,
      clozapine-induced myocarditis continues to cause deaths in Australia, and the
      risk is a barrier to prescription of this effective drug for the treatment of
      schizophrenia. This study was designed to identify clinical and phenotypic risk
      factors for clozapine-induced myocarditis. METHOD: Possible cases of clozapine
      related myocarditis occurring between June 1993 and November 2009 and a
      comparative group of controls taking clozapine for at least 45days without
      cardiac disease were documented from the patients' medical records. RESULTS: 105
      cases, with time to onset of 10-33days, and 296 controls were included in the
      study. In multivariate analysis, the risk of myocarditis increased by 26% for
      each additional 250mg of clozapine administered in the first nine days of
      clozapine titration (odds ratio 1.26; 95% confidence interval 1.02-1.55; p=0.03)
      and concomitant sodium valproate more than doubled the risk (2.59; 1.51-4.42;
      0.001). Further, each successive decade in age was associated with a 31% increase
      in risk (1.31; 1.07-1.60; 0.009). Nevertheless, 33 cases received less than 920mg
      of clozapine during the first nine days of dose titration, did not take sodium
      valproate and were aged less than 40years; and nine control patients received
      sodium valproate and more than 920mg of clozapine in the first nine days without
      developing myocarditis. CONCLUSIONS: Clozapine should be initiated by slow dose
      titration and sodium valproate is best avoided, if clinically feasible, during
      this period. All patients commencing clozapine should be monitored for
      myocarditis up to Day 28.

PMID- 23010489
TI  - Distinguishing grammatical constructions with fMRI pattern analysis.
AB  - All linguistic and psycholinguistic theories aim to provide psychologically valid
      analyses of particular grammatical patterns and the relationships that hold among
      them. Until recently, no tools were available to distinguish neural correlates of
      particular grammatical constructions that shared the same content words,
      propositional meaning, and degree of surface complexity, such as the dative
      (e.g., Sally gave the book to Joe) and the ditransitive (e.g., Sally gave Joe a
      book). We report the first fMRI data that distinguish such closely related,
      abstract grammatical patterns. Multi-voxel pattern analysis (MVPA) proved capable
      of discriminating at above-chance levels between activity patterns arising during
      reading of dative and ditransitive sentences. Region-of-interest analyses reveal
      that the union of certain language-relevant areas, anterior and posterior BA22,
      BA44/45 and BA47, yield classification accuracy above chance and above that of
      control conditions in the left hemisphere but not in the right. Looking more
      closely at the LH ROIs, we find that the combination of areas aBA22 and BA47 is
      sufficient to distinguish the two constructions better than the controls and
      better than chance. The fact that both of these areas-particularly BA47-have been
      implicated in semantics, lends support to claims that the two constructions are
      distinguishable semantically. More generally, the ability to distinguish closely
      related grammatical constructions using MVPA offers the promise of addressing
      traditional theoretical questions on a neuroscientifically grounded basis.

PMID- 23010491
TI  - Structure of building blocks in amylopectins.
AB  - Building blocks represent the smallest, branched units found inside clusters of
      amylopectins. The building blocks from clusters of 10 different amylopectins,
      representing a wide variety of plants, were isolated and size-fractionated. The
      unit chain compositions were then analysed. It was found that the number of
      chains in building blocks increased in proportion to their size similarly in all
      samples regardless plant source. The smallest blocks (DP 5-9) consisted of 2
      chains and the largest blocks (DP >=45), of which generally only little existed,
      possessed >=10 chains. Generally, the degree of branching increased with building
      block size, but the organisation of chains inside the blocks was unique for each
      sample. Nevertheless, compared to other plants, amylopectins from cereals
      (represented by rye, oats, rice and waxy maize) possessing elevated number of the
      shortest internal B-chains (DP 3-7), tended to have blocks with a lower ratio of
      A:B-chains, indicative of a preferred Haworth type of structure as opposed to the
      Staudinger configuration.

PMID- 23010490
TI  - Regulation of cnidarian-dinoflagellate mutualisms: Evidence that activation of a
      host TGFbeta innate immune pathway promotes tolerance of the symbiont.
AB  - Animals must manage interactions with beneficial as well as detrimental microbes.
      Immunity therefore includes strategies for both resistance to and tolerance of
      microbial invaders. Transforming growth factor beta (TGFbeta) cytokines have many
      functions in animals including a tolerance-promoting (tolerogenic) role in
      immunity in vertebrates. TGFbeta pathways are present in basal metazoans such as
      cnidarians but their potential role in immunity has never been explored. This
      study takes a two-part approach to examining an immune function for TGFbeta in
      cnidarians. First bioinformatic analyses of the model anemone Aiptasia pallida
      were used to identify TGFbeta pathway components and explore the hypothesis that
      an immune function for TGFbetas existed prior to the evolution of vertebrates. A
      TGFbeta ligand from A. pallida was identified as one that groups closely with
      vertebrate TGFbetas that have an immune function. Second, cellular analyses of A.
      pallida were used to examine a role for a TGFbeta pathway in the regulation of
      cnidarian-dinoflagellate mutualisms. These interactions are stable under ambient
      conditions but collapse under elevated temperature, a phenomenon called cnidarian
      bleaching. Addition of exogenous human TGFbeta suppressed an immune response
      measured as LPS-induced nitric oxide (NO) production by the host. Addition of
      anti-TGFbeta to block a putative TGFbeta pathway resulted in immune stimulation
      and a failure of the symbionts to successfully colonize the host. Finally,
      addition of exogenous TGFbeta suppressed immune stimulation in heat-stressed
      animals and partially abolished a bleaching response. These findings suggest that
      the dinoflagellate symbionts somehow promote host tolerance through activation of
      tolerogenic host immune pathways, a strategy employed by some intracellular
      protozoan parasites during their invasion of vertebrates. Insight into the
      ancient, conserved nature of host-microbe interactions gained from this cnidarian
      dinoflagellate model is valuable to understanding the evolution of immunity and
      its role in the regulation of both beneficial and detrimental associations.

PMID- 23010492
TI  - Glycosidic constituents from the roots and rhizomes of Melicope pteleifolia.
AB  - Seven new diglycosidic constituents, named pteleifosides A-G (1-7), along with
      ten known glycosides, were isolated from the roots and rhizomes of Melicope
      pteleifolia (Champ. ex Benth.) T. Hartley. The structures of the isolated
      compounds were established on the basis of chemical and spectroscopic methods,
      mainly 1D and 2D NMR data and mass spectrometry.

PMID- 23010493
TI  - A prominent R wave in V(1) but not in V(2) is a specific sign of a large lateral
      transmural infarction.
AB  - INTRODUCTION AND OBJECTIVES: In the absence of right ventricular hypertrophy or
      bundle-branch block, a prominent R wave in V(1) or V(2) is considered to reflect
      a lateral myocardial infarction. We investigated the differences in infarct
      location, size and transmural extent between patients with prominent R wave in
      V(1) and those with prominent R wave in V(2). METHODS: We studied 50 patients
      with a previous first infarction involving left ventricular inferior and/or
      lateral wall at contrast-enhanced magnetic resonance. RESULTS: A prominent R wave
      in V(1) was present in 8 patients (16%), in V(2) in 23 (46%). At magnetic
      resonance, the infarction involved the inferior wall in 11 patients (22%), the
      lateral wall in 6 (12%), and both walls in 33 patients (66%). The sensitivity of
      a prominent R wave in V(1) in detecting a lateral infarction was low (17.9%),
      while the specificity was high (90.9%). The sensitivity and specificity of a
      prominent R wave in V(2) were 46.2% and 54.5%, respectively. In patients with a
      prominent R wave in V(1), infarct size and lateral and transmural extent were
      greater than in patients without this pattern (P<.005, <.001, and <.05,
      respectively); conversely, infarct size and transmural extent in the inferior
      wall and in its basal-posterior segment were not significantly different. In
      patients with a prominent R wave in V(2), infarct size, lateral and transmural
      extent were not different from patients without this pattern. CONCLUSIONS: Only a
      prominent R wave in V(1) is a specific sign of large and transmural lateral
      infarction.

PMID- 23010494
TI  - Hepatic mitochondrial dysfunction induced by fatty acids and ethanol.
AB  - Understanding the key aspects of the pathogenesis of alcoholic fatty liver
      disease particularly alterations to mitochondrial function remains to be
      resolved. The role of fatty acids in this regard requires further investigation
      due to their involvement in fatty liver disease and obesity. This study aimed to
      characterize the early effects of saturated and unsaturated fatty acids alone on
      liver mitochondrial function and during concomitant ethanol exposure using
      isolated liver mitochondria and VA-13 cells (Hep G2 cells that efficiently
      express alcohol dehydrogenase). Liver mitochondria or VA-13 cells were treated
      with increasing concentrations of palmitic or arachidonic acid (1 to 160 MUM) for
      24 h with or without 100 mM ethanol. The results showed that in isolated liver
      mitochondria both palmitic and arachidonic acids significantly reduced state 3
      respiration in a concentration-dependent manner (P<0.001), implicating their
      ionophoric activities. Increased ROS production occurred in a dose-dependent
      manner especially in the presence of rotenone (complex I inhibitor), which was
      significantly more prominent in arachidonic acid at 80 MUM (+970%, P<0.001) than
      palmitic acid (+40%, P<0.01). In VA-13 cells, ethanol alone and both fatty acids
      (40 MUM) were able to decrease the mitochondrial membrane potential and cellular
      ATP levels and increase lipid formation. ROS production was significantly
      increased with arachidonic acid (+110%, P<0.001) exhibiting a greater effect than
      palmitic acid (+39%, P<0.05). While in the presence of ethanol, the drop in the
      mitochondrial membrane potential, cellular ATP levels, and increased lipid
      formation were further enhanced by both fatty acids, but with greater effect in
      the case of arachidonic acid, which also correlated with significant cytotoxicity
      (P<0.001). This study confirms the ability of fatty acids to promote
      mitochondrial injury in the development of alcoholic fatty liver disease.

PMID- 23010496
TI  - In vivo redox state of human thioredoxin and redox shift by the histone
      deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA).
AB  - The cytosolic thioredoxin (Trx1) system is essential for maintaining a reduced
      intracellular environment, via reduced Trx1 acting as a general protein disulfide
      reductase. Trx1 is implicated in cell signaling such as proliferation, DNA
      synthesis, enzyme activation, cell cycle regulation, transcription, gene
      activation, and prevention of apoptosis. Human Trx1 contains the active-site
      cysteines, Cys32 and Cys35, and three additional structural cysteines, Cys62,
      Cys69, and Cys73, that regulate Trx1 structure and activity via a second
      disulfide formation, S-glutathionylation or S-nitrosylation. The present study
      uses an electrophoretic redox Western blot method to analyze the oxidation state
      of Trx1 in vivo separating the protein-changed isoform following alkylation with
      iodoacetic acid in 8M urea. Treatment with the histone deacetylase inhibitor SAHA
      increased Trx1 inhibitor thioredoxin interacting protein (Txnip) levels,
      decreased Trx1 activity, and switched the Trx1 oxidation state toward a more
      oxidized one, as a result of complex formation with Trx1, and increased reactive
      oxygen species (ROS). SAHA is currently in clinical trials for cancer treatment,
      and one possible mechanism for its anticancer effect is via effects on the Trx1
      system. Determining the exact oxidation state of human cytosolic Trx1 may be
      useful in developing and evaluating cancer drugs and antioxidant agents.

PMID- 23010495
TI  - Mitochondrial handling of excess Ca2+ is substrate-dependent with implications
      for reactive oxygen species generation.
AB  - The mitochondrial electron transport chain is the major source of reactive oxygen
      species (ROS) during cardiac ischemia. Several mechanisms modulate ROS
      production; one is mitochondrial Ca(2+) uptake. Here we sought to elucidate the
      effects of extramitochondrial Ca(2+) (e[Ca(2+)]) on ROS production (measured as
      H(2)O(2) release) from complexes I and III. Mitochondria isolated from guinea pig
      hearts were preincubated with increasing concentrations of CaCl(2) and then
      energized with the complex I substrate Na(+) pyruvate or the complex II substrate
      Na(+) succinate. Mitochondrial H(2)O(2) release rates were assessed after giving
      either rotenone or antimycin A to inhibit complex I or III, respectively. After
      pyruvate, mitochondria maintained a fully polarized membrane potential (DeltaPsi;
      assessed using rhodamine 123) and were able to generate NADH (assessed using
      autofluorescence) even with excess e[Ca(2+)] (assessed using CaGreen-5N), whereas
      they remained partially depolarized and did not generate NADH after succinate.
      This partial DeltaPsi depolarization with succinate was accompanied by a large
      release in H(2)O(2) (assessed using Amplex red/horseradish peroxidase) with later
      addition of antimycin A. In the presence of excess e[Ca(2+)], adding cyclosporin
      A to inhibit mitochondrial permeability transition pore opening restored DeltaPsi
      and significantly decreased antimycin A-induced H(2)O(2) release. Succinate
      accumulates during ischemia to become the major substrate utilized by cardiac
      mitochondria. The inability of mitochondria to maintain a fully polarized
      DeltaPsi under excess e[Ca(2+)] when succinate, but not pyruvate, is the
      substrate may indicate a permeabilization of the mitochondrial membrane, which
      enhances H(2)O(2) emission from complex III during ischemia.

PMID- 23010497
TI  - Histone deacetylase 6 (HDAC6) plays a crucial role in p38MAPK-dependent induction
      of heme oxygenase-1 (HO-1) in response to proteasome inhibition.
AB  - The proteasome is responsible for the degradation of polyubiquitinated proteins.
      Inhibition of the proteasome leads to an accumulation of polyubiquitinated
      proteins and thus to an impairment of the cellular protein homeostasis. To
      prevent cellular damage on proteasome inhibition there is an up-regulation of
      several heat shock proteins (Hsps), including Hsp27, Hsp70, and heme oxygenase-1
      (HO-1). It was demonstrated that the induction of classical Hsps, such as Hsp27
      and Hsp70, is dependent on a HDAC6-dependent mechanism which releases HSF-1 and
      induces the expression of newly synthesized Hsps. In this study we demonstrate
      that the up-regulation of HO-1 on proteasome inhibition is mediated by p38MAPK
      and Nrf-2. Interestingly we found additional evidence, proving the involvement of
      HDAC6 in the up-regulation of HO-1. By using RNAi technologies against HDAC6 we
      demonstrate that there is a lack of the expected induction of HO-1, Nrf-2, and
      phosphorylated p38 (pp38) after proteasome inhibition. Furthermore, we can show
      that p38 is acetylated in unstressed cells and is a good substrate for HDAC6
      mediated deacetylation. Therefore, we propose that on proteasome inhibition HDAC6
      deacetylates p38, allowing the subsequent phosphorylation of p38 and resultant
      activation of NRF-2. NRF-2 enters the nucleus and functions as a transcription
      factor for HO-1.

PMID- 23010498
TI  - Thyroid hydrogen peroxide production is enhanced by the Th2 cytokines, IL-4 and
      IL-13, through increased expression of the dual oxidase 2 and its maturation
      factor DUOXA2.
AB  - The dual oxidases (DUOX) 1 and 2 constitute the major components of the thyroid
      H(2)O(2)-generating system required for thyroid hormone synthesis. With their
      maturation factor, DUOXA1 or DUOXA2, they share the same bidirectional promoter
      allowing coexpression of DUOX/DUOXA in the same tissue. However, the molecular
      mechanisms regulating their transcription in the human thyroid gland are not well
      characterized yet. Inflammatory molecules associated with autoimmune thyroid
      diseases have been shown to repress the thyroid function by down-regulating the
      expression of the major thyroid differentiation markers. These findings led us to
      investigate the effects of the main cytokines involved in Hashimoto thyroiditis
      (IFN-gamma) and Graves' diseases (IL-4/IL-13) on the transcriptional regulation
      of DUOX and their corresponding DUOXA genes in thyroid cells. Human thyrocytes
      exposed to the Th2 cytokines IL-4 and IL-13 showed up-regulation of DUOX2 and
      DUOXA2 genes but not DUOX1/DUOXA1. The DUOX2/DUOXA2 induction was rapid and
      associated with a significant increase of calcium-stimulated extracellular
      H(2)O(2) generation. IFN-gamma treatment inhibited DUOX gene expression and
      repressed the Th2 cytokine-dependent DUOX2/DUOXA2 expression. In another DUOX
      expressing model, the human intestinal Caco-2 cell line, expression of DUOX2 and
      DUOXA2 mRNA was also positively modulated by IL-4 and IL-13. Analysis of the IL-4
      signaling pathway revealed that the JAK1-STAT6 cascade activated by the IL-4 type
      2 receptor is required for DUOX2/DUOXA2 induction. The present data open new
      perspectives for a better understanding of the pathophysiology of thyroid
      autoimmune diseases considering DUOX2-mediated oxidative damages.

PMID- 23010499
TI  - Internalization and induction of antioxidant messages by microvesicles contribute
      to the antiapoptotic effects on human endothelial cells.
AB  - Microvesicles are plasma membrane-derived fragments released from various cell
      types during activation and/or apoptosis and posses the ability to deliver
      biological information between cells. Microvesicles generated from T lymphocytes
      undergoing activation and apoptosis bear the morphogen Sonic Hedgehog, and exert
      a beneficial potential effect on the cardiovascular system through their dual
      capacity to increase nitric oxide and reduce reactive oxygen species production.
      This study investigated the effect of microvesicles on the apoptosis of human
      umbilical vein endothelial cells triggered by actinomycin D. Microvesicles
      prevented apoptosis induced by actinomycin D by modulating reactive oxygen
      species production: during the early phase of apoptosis, microvesicles might act
      directly as reactive oxygen species scavengers, owing to their ability to carry
      active antioxidant enzymes, catalase, and isoforms of the superoxide dismutase.
      Furthermore, their effects were associated with the ability to increase the
      expression of manganese-superoxide dismutase in endothelial cells, through the
      internalization process. Interestingly, microvesicles bearing Sonic Hedgehog
      induced cytoprotection in endothelial cells through the activation of the Sonic
      Hedgehog pathway. These findings provide additional evidence that microvesicles
      from T lymphocytes exert their vasculoprotective effects by promoting
      internalization and induction of antioxidant messages to the endothelial
      monolayer.

PMID- 23010500
TI  - Human skeletal muscle releases leptin in vivo.
AB  - Leptin is considered an adipokine, however, cultured myocytes have also been
      found to release leptin. Therefore, as proof-of-concept we investigated if human
      skeletal muscle synthesized leptin by measuring leptin in skeletal muscle
      biopsies. Following this, we quantified human skeletal muscle and adipose tissue
      leptin release in vivo. We recruited 16 healthy male human participants.
      Catheters were inserted into the femoral artery and vein draining skeletal
      muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose
      tissue. By combining the veno-arterial differences in plasma leptin with
      measurements of blood flow, leptin release from both tissues was quantified. To
      induce changes in leptin, the participants were infused with either saline or
      adrenaline in normo-physiological concentrations. The presence of leptin in
      skeletal muscle was confirmed by western blotting. Leptin was released from leg
      skeletal muscle (50.6 +/- 12 ng min(-1)) and the pattern of release was different
      from subcutaneous adipose tissue. Moreover, during adrenaline infusion the leptin
      release from leg skeletal muscle was strongly suppressed (20.5 +/- 7.9 ng min(
      1), p<0.017), whereas the release from fat was unaltered. During saline infusion
      the adipose tissue release averaged 0.8 +/- 0.3 ng min(-1) 100g tissue(-1)
      whereas skeletal muscle release was 0.5 +/- 0.1 ng min(-1) 100g tissue(-1). In
      young healthy humans, skeletal muscle contribution to whole body leptin
      production could be substantial given the greater mass of muscle compared to fat.
      An understanding of the role that leptin plays in skeletal muscle metabolism may
      prove important in light of several late-phase trials with recombinant leptin as
      an anti-obesity drug.

PMID- 23010501
TI  - Need for clarification of data in a recent meta-analysis on vascular endothelial
      growth factor (VEGF) and risk of breast cancer.

PMID- 23010502
TI  - Pretreatment circulating serum cytokines associated with follicular and diffuse
      large B-cell lymphoma: a clinic-based case-control study.
AB  - BACKGROUND: Abnormal immune function is a key factor in predisposition to non
      Hodgkin lymphoma (NHL). We evaluated the association of 30 cytokines individually
      and as a profile with diffuse large B-cell (DLBCL) and follicular (FL) lymphomas.
      METHODS: We used a multiplexed assay to measure 30 cytokine concentrations in pre
      treatment serum in a case-control study of 234 FL, 188 DLBCL, and 400 control
      participants. Unconditional logistic regression was used to estimate odds ratios
      (ORs) and 95% confidence intervals (CIs) adjusted for age and sex, and polytomous
      regression was used to evaluate heterogeneity between FL and DLBCL. Principal
      components analysis (PCA) was used to assess cytokine profiles associated with FL
      and DLBCL. RESULTS: In single cytokine modeling, we found that 12 of the 30
      circulating serum cytokines were significantly (P<0.05) associated with FL and/or
      DLBCL after accounting for multiple testing (q<0.05). Soluble IL-2R (sIL-2R) had
      the strongest association with both FL (OR=6.0 for highest versus lowest tertile,
      95% CI 3.8-9.5; p-trend=1.8 * 10(-21)) and DLBCL (OR=7.6, 95% CI 4.5-13.1; p
      trend=7.2 * 10(-20)). IL1RA and IL-12p40 also showed similar associations for
      DLBCL and FL. In contrast, HGF, MIG, and MIP-1alpha had a stronger association
      with DLBCL compared to FL, and IL-6, IL-8, IL-10, IFN-gamma, IP-10, and VEGF were
      only statistically significantly associated with DLBCL after accounting for
      multiple testing. However, in PCA modeling, a cytokine profile based on sIL-2R,
      IL-1RA, MIG, IP-10, IL-8, and IL-12p40 explained most of the variability between
      controls and both FL and DLBCL. CONCLUSIONS: We identified some cytokines unique
      to DLBCL, but overall cytokine associations were more similar than distinct for
      DLBCL and FL. While these data are limited by concerns of reverse causality, they
      do suggest cytokines and cytokine profiles that can be prioritized in future
      studies.

PMID- 23010504
TI  - [Management of neurovascular disease in Neurosurgical Departments in Spain].

PMID- 23010503
TI  - Obesity and IL-6 interact in modulating the response to endotoxemia in mice.
AB  - Obesity is associated with elevated levels of IL-6. High IL-6 is prognostic of
      mortality in sepsis, while controversial data link obesity to sepsis outcome. We
      used Lean and diet-induced obese (DIO) WT and IL-6 KO mice to investigate the
      interaction between obesity and IL-6 in endotoxemia. Circulating levels of IL-6
      were significantly higher in WT DIO versus WT Lean mice receiving LPS (2.5
      MUg/mouse, ip). Obesity lead to greater weight loss in response to LPS, with IL-6
      deficiency being partially protective. Plasma TNFalpha, IFNgamma, Galectin-3 and
      leptin were significantly elevated in response to LPS and were each
      differentially affected by obesity and/or IL-6 deficiency. Plasma Galectin-1 and
      adiponectin were significantly suppressed by LPS, with obesity and IL-6
      deficiency modulating the response. However, LPS comparably increased IL-10
      levels in each group. Leukopenia with relative neutrophilia and thrombocytopenia
      developed in each group after injection of LPS, with obesity and genotype
      affecting the kinetics, but not the magnitude, of the response. Hepatic induction
      of the acute-phase protein SAA by LPS was not affected by obesity or IL-6
      deficiency, although baseline levels were highest in WT DIO mice. Injection of
      LPS significantly increased hepatic mRNA expression of PAI-1 in Lean WT and Lean
      KO mice, while it suppressed the high baseline levels observed in the liver of
      DIO WT and DIO KO mice. Thus, both IL-6 and obesity modulate the response to
      endotoxemia, suggesting a complex interaction that needs to be considered when
      evaluating the effect of obesity on the outcome of septic patients.

PMID- 23010505
TI  - [Reply "Management of neurovascular disease in Neurosurgical Departments in
      Spain"].

PMID- 23010507
TI  - How do mandibles sense? The sensory apparatus of larval mandibles in Palaemon
      elegans Rathke, 1837 (Decapoda, Palaemonidae).
AB  - The mandibles of decapod zoea-I larvae are robustly built masticating mouthparts
      equipped with several processes and spines. Superficial examination of these
      sturdy, inflexible structures can suggest that they are lacking sensory
      receptors. However, detailed TEM analysis of their ultrastructure revealed up to
      11 sensillar cell clusters on the gnathal edges of the mandibles of the zoea-I in
      Palaemon elegans Rathke, 1837. Based on ultrastructural criteria we distinguish 7
      types of sensilla: mechanoreceptors, chemoreceptors and mechano- and
      chemoreceptors. One sensory unit located at the base of the 'lacinia mobilis'
      exhibits the typical features of a crustacean mechanosensitive sensillum with an
      external seta and corresponding ultrastructure. Another unit shows features
      indicating bimodal contact chemosensitivity. A third one is similar to known
      olfactory chemoreceptors. Using the concept of modality-specific structures we
      analyse the structure and functional morphology of each sensillum, and give a
      comprehensive overview of the sensory abilities of zoea mandibles. We take a
      closer look at the ultrastructure of the 'lacinia mobilis', providing further
      features to trace its evolutionary history in Decapoda, and thus contributing to
      a better understanding of malacostracan phylogeny.

PMID- 23010508
TI  - The skeletomuscular system of the larva of Drosophila melanogaster
      (Drosophilidae, Diptera): a contribution to the morphology of a model organism.
AB  - The morphological features of the third instar larva of the most important insect
      model, Drosophila melanogaster, are documented for the first time using a broad
      spectrum of modern morphological techniques. External structures of the body
      wall, the cephaloskeleton, and the musculature are described and illustrated.
      Additional information about other internal organs is provided. The systematic
      implications of the findings are discussed briefly. Internal apomorphic features
      of Brachycera and Cyclorrhapha are confirmed for Drosophila. Despite the
      intensive investigations of the phylogeny of the megadiverse Diptera,
      evolutionary reconstructions are still impeded by the scarcity of anatomical data
      for brachyceran larvae. The available morphological information for the life
      stages of three insect model organisms -D. melanogaster (Diptera, Drosophilidae),
      Manduca sexta (Lepidoptera, Sphingidae) and Tribolium castaneum (Coleoptera,
      Tenebrionidae) - is addressed briefly. The usefulness of a combination of
      traditional and innovative techniques for an optimized acquisition of anatomical
      data for different life stages is highlighted.

PMID- 23010510
TI  - Jak-STAT regulation of cyst stem cell development in the Drosophila testis.
AB  - Establishment and maintenance of functional stem cells is critical for organ
      development and tissue homeostasis. Little is known about the mechanisms
      underlying stem establishment during organogenesis. Drosophila testes are among
      the most thoroughly characterized systems for studying stem cell behavior, with
      germline stem cells (GSCs) and somatic cyst stem cells (CySCs) cohabiting a
      discrete stem cell niche at the testis apex. GSCs and CySCs are arrayed around
      hub cells that also comprise the niche and communication between hub cells, GSCs,
      and CySCs regulates the balance between stem cell maintenance and
      differentiation. Recent data has shown that functional, asymmetrically dividing
      GSCs are first established at ~23 h after egg laying during Drosophila testis
      morphogenesis (Sheng et al., 2009). This process correlates with coalescence of
      the hub, but development of CySCs from somatic gonadal precursors (SGPs) was not
      examined. Here, we show that functional CySCs are present at the time of GSC
      establishment, and that Jak-STAT signaling is necessary and sufficient for CySC
      maintenance shortly thereafter. Furthermore, hyper-activation of Jak in CySCs
      promotes expansion of the GSC population, while ectopic Jak activation in the
      germline induces GSC gene expression in GSC daughter cells but does not prevent
      spermatogenic differentiation. Together, these observations indicate that,
      similar to adult testes, Jak-STAT signaling from the hub acts on both GSCs and
      CySC to regulate their development and differentiation, and that additional
      signaling from CySCs to the GSCs play a dominant role in controlling GSC
      maintenance during niche formation.

PMID- 23010511
TI  - Transcriptome analysis of Drosophila CNS midline cells reveals diverse
      peptidergic properties and a role for castor in neuronal differentiation.
AB  - One of the key aspects of neuronal differentiation is the array of
      neurotransmitters and neurotransmitter receptors that each neuron possesses. One
      important goal of developmental neuroscience is to understand how these
      differentiated properties are established during development. In this paper, we
      use fluorescence activated cell sorting and RNA-seq to determine the
      transcriptome of the Drosophila CNS midline cells, which consist of a small
      number of well-characterized neurons and glia. These data revealed that midline
      cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and
      31 small-molecule neurotransmitter receptor genes. In situ hybridization and high
      resolution confocal analyses were carried-out to determine the midline cell
      identity for these neuropeptides and the neuropeptide receptors. The results
      revealed a surprising level of diversity. Neuropeptide genes are expressed in a
      variety of midline cell types, including motoneurons, GABAergic interneurons, and
      midline glia. These data revealed previously unknown functional differences among
      the highly-related iVUM neurons. There also exist segmental differences in
      expression for the same neuronal sub-type. Similar experiments on midline
      expressed neuropeptide receptor genes reveal considerable diversity in synaptic
      inputs. Multiple receptor types were expressed in midline interneurons and
      motoneurons, and, in one case, link feeding behavior to gut peristalsis and
      locomotion. There were also segmental differences, variations between the 3
      iVUMs, and three hormone receptor genes were broadly expressed in most midline
      cells. The Drosophila Castor transcription factor is present at high levels in
      iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor
      gene. Genetic and misexpression experiments indicated that castor specifically
      controls expression of the short neuropeptide F precursor gene, but does not
      affect iVUM cell fate or expression of Gad1. This indicates a novel function for
      castor in regulating neuropeptide gene expression.

PMID- 23010512
TI  - Liver graft pretreated in vivo or ex vivo by gamma-aminobutyric acid receptor
      regulation.
AB  - BACKGROUND: gamma-Aminobutyric acid exists throughout the body, and the brain
      gamma-aminobutyric acid receptor (GABAR) regulation reduces oxidative stress
      (OS). Effects of GABAR regulation in the liver are unknown. Ischemia or
      reperfusion injury after orthotopic liver transplantation (OLT) or shear stress
      after split OLT (SOLT) with a small-for-size graft causes OS-induced graft
      damage. Here, the strategic potential of graft pretreatment in vivo and ex vivo
      by GABAR regulation was investigated. MATERIALS AND METHODS: Recipient rats were
      divided into seven groups according to the graft pretreatments and graft types:
      (1) laparotomy, (2) OLT, (3) GABAR regulation in vivo and OLT, (4) GABAR
      regulation ex vivo and OLT, (5) SOLT, (6) GABAR regulation in vivo and SOLT, and
      (7) GABAR regulation ex vivo and SOLT. Survival study, biochemical assays,
      histopathologic or immunohistologic assessments, and Western blotting were
      performed at 6 h after OLT or SOLT. RESULTS: Graft pretreatment in vivo prolonged
      survival after SOLT. Histopathologic and biochemical profiles verified that graft
      pretreatment in vivo reduced graft damage after OLT or SOLT.
      Immunohistologically, graft pretreatment in vivo prevented apoptotic inductions
      after OLT or SOLT. The 4-hydroxynonenal confirmed the OS after OLT or SOLT, and
      graft pretreatment in vivo improved the OS. Graft pretreatment in vivo decreased
      ataxia-telangiectasia-mutated kinase and H2AX after OLT or SOLT. Graft
      pretreatment in vivo increased phosphatidylinositol 3 kinase and Akt after SOLT.
      In contrast, GABAR regulation ex vivo did not work. CONCLUSIONS: Graft
      pretreatment in vivo, not ex vivo, prevented the ischemia or reperfusion injury
      mediated OS after OLT or SOLT via the ataxia-telangiectasia-mutated kinase/H2AX
      pathway and the shear stress-mediated OS after SOLT with small-for-size graft via
      the phosphatidylinositol 3 kinase/Akt pathway.

PMID- 23010513
TI  - Tissue-engineering repair of extrahepatic bile ducts.
AB  - BACKGROUND: In recent years, with the widespread use of laparoscopic
      cholecystectomy and liver transplantation, complications involving the biliary
      system are increasing. All techniques available have a high risk of recurrence or
      high-morbidity problems. We developed a three-dimensional collagen duct modified
      with agarose hydrogel, to substitute the affected extrahepatic bile duct.
      MATERIALS AND METHODS: We used it in 40 guinea pigs and studied the histology and
      physiology at 4 wk, 3, and 6 mo after transplantation. Blood test, histologic
      techniques, and cholangiography were performed in all of them. RESULTS: All
      experimental animals survived up to their sacrifices. Our graft showed highly
      potential applications to treat hepatobiliary diseases that require surgery.

PMID- 23010509
TI  - Using mouse models of autism spectrum disorders to study the neurotoxicology of
      gene-environment interactions.
AB  - To better study the role of genetics in autism, mouse models have been developed
      which mimic the genetics of specific autism spectrum and related disorders. These
      models have facilitated research on the role genetic susceptibility factors in
      the pathogenesis of autism in the absence of environmental factors. Inbred mouse
      strains have been similarly studied to assess the role of environmental agents on
      neurodevelopment, typically without the complications of genetic heterogeneity of
      the human population. What has not been as actively pursued, however, is the
      methodical study of the interaction between these factors (e.g., gene and
      environmental interactions in neurodevelopment). This review suggests that a
      genetic predisposition paired with exposure to environmental toxicants plays an
      important role in the etiology of neurodevelopmental disorders including autism,
      and may contribute to the largely unexplained rise in the number of children
      diagnosed with autism worldwide. Specifically, descriptions of the major mouse
      models of autism and toxic mechanisms of prevalent environmental chemicals are
      provided followed by a discussion of current and future research strategies to
      evaluate the role of gene and environment interactions in neurodevelopmental
      disorders.

PMID- 23010514
TI  - Prognostic value of circulating cytokines for stage III colon cancer.
AB  - BACKGROUND: This study was to determine preoperative serum levels of epidermal
      growth factor (EGF), interleukin-6 (IL-6), and C-reactive protein (CRP) in stage
      III colon cancer and correlate them with disease status and prognosis. The
      circulating EGF in correlation with primary site epidermal growth factor receptor
      (EGFR) was also evaluated. METHODS: Seventy-seven patients with curatively
      resected stage III colon cancer were selected for analysis. Enzyme-linked
      immunosorbent assay was used to determine EGF and IL-6 serum levels, and serum
      CRP levels were measured via immunoturbidimetry. EGFR expression was observed
      with immunohistochemical studies. RESULTS: The median levels of EGFR, IL-6, and
      CRP were 189.4 pg/mL, 9.09 pg/mL, and 1.4 mg/mL, respectively. The factors
      related to recurrence with statistical significance included positive node status
      (P = 0.041), lymphovascular invasion (P = 0.001), and preoperative IL-6 level >=9
      pg/mL (P = 0.020). CRP and EGF levels were not significantly associated with
      disease-free survival rates (P = 0.438 and P = 0.309, respectively). Multivariate
      analysis using Cox's proportion model revealed that lymph node status was the
      single independent prognostic factor for predicting time until recurrence (odds
      ratio, 4.99; 95% confidence interval, 1.09-22.91; P = 0.038). CONCLUSION: IL-6
      expression in stage III colon cancer patients appears to be a prognostic marker
      of tumor behavior. No correlations between serum EGF concentrations and tumor
      EGFR positivity were found in this study.

PMID- 23010515
TI  - 17beta-Estradiol reappropriates mass lost to the hypermetabolic state in
      thermally injured rats.
AB  - BACKGROUND: The hypermetabolic response to severe thermal injury is unlike any
      physiologic response seen in medicine. While some parallels can be drawn to shock
      and sepsis states, this response is typified by its intensity and duration. Our
      group has been interested in the myriad effects of estrogens after injury,
      specifically the ability of estrogens to reduce inflammatory responses. Given
      this, and the known link between severe inflammation and the hypermetabolic
      response, we examined the effects of a single dose of 17beta estradiol
      administered after a severe thermal injury in rats. METHODS: Twelve male Sprague
      Dawley rats were subject to either a sham burn or a 40% total body surface area
      burn, followed by fluid resuscitation. Burned animals were divided into a vehicle
      and treatment group, with injections given 15 min after the injury. Animals were
      monitored for a period of 45 d, with markers of hypermetabolism (weight, fecal
      output, food intake, and serum insulin and glucose) measured daily. RESULTS: We
      identified a significant difference in daily measured weights between the burned
      groups. We observed a sparing of body mass during the acute phase lasting 2 wk
      after the injury and an improved recovery phase during the remainder of the
      study. Glucose and insulin levels during the first week of the study did not
      differ between the treatment groups. CONCLUSION: Estrogen may have a role in
      preserving body mass after severe thermal injury. Further studies are required to
      determine if this spared body mass composition.

PMID- 23010516
TI  - PNPLA3 Ile148Met variant and hepatocellular carcinoma: a matter of fat.

PMID- 23010517
TI  - What is the ideal stent as initial intervention for malignant gastric outlet
      obstruction?
AB  - BACKGROUND: Self-expandable metal stents are effective palliation for malignant
      gastric outlet obstruction. The aims of study were to evaluate efficacy and
      safety of double-layered Comvi, uncovered and covered stent to find out protocols
      which enhance stent patency. METHODS: We retrospectively analysed data from 224
      patients who underwent endoscopic stent placement for malignant gastric outlet
      obstruction caused by stomach cancer from 2006 to 2011. Technical and clinical
      success rates were evaluated and clinical outcomes were compared according to
      stent types and chemotherapy. RESULTS: The overall technical and clinical success
      rates were achieved in 99.6% and 80.4%, respectively without immediate
      complications. The clinical success rate was not significantly different between
      three groups. The median stent patency time was 156 days [interquartile range 66
      279] without differences between groups. The 4-, 8-, and 12-week patency rates
      were 89.4%, 77.3%, and 61.2%, respectively with no differences between groups.
      The re-stenosis of stent frequently occurred in the case of the uncovered stents,
      while migration was more likely to be observed for the covered and Comvi stent.
      Chemotherapy significantly lowered re-intervention rates, especially in uncovered
      stents. CONCLUSIONS: Patency rates are significantly improved by combining the
      use of uncovered stent with follow-up chemotherapy treatment, which retains the
      advantages of the mechanical and chemical aspects of stent and chemotherapy,
      respectively.

PMID- 23010518
TI  - New trends in inflammatory bowel disease epidemiology and disease course in
      Eastern Europe.
AB  - Trends in current epidemiological data suggest that the incidence of inflammatory
      bowel diseases is changing. Eastern Europe previously was seen as a low incidence
      area; however, new data confirm that incidence and prevalence are quickly
      increasing in some countries, reaching moderate-to-high incidence as reported in
      Western European countries. The quality of the studies also improved. Recently,
      data became available on the natural history of the disease from Eastern European
      countries. Current trends are similar to those reported from Western Europe and
      North America, including less complicated disease at diagnosis, accelerated use
      of immunomodulators and decreased need for surgery in Crohn's disease, more cases
      of proctitis and relatively low colorectal cancer risk in ulcerative colitis. In
      addition, in-depth analysis of disease course enabled the identification of
      possible predictive factors leading to some novel findings, such as the
      association between the decline in surgery risk and early treatment strategy. In
      contrast, some unexplained differences exist, such as the low overall colectomy
      risk in ulcerative colitis.

PMID- 23010519
TI  - [The retina as a biological marker of neuronal damage].

PMID- 23010520
TI  - [Comparison of three optical coherence tomography devices, one time-domain and
      two fourier-domain, for the estimation of the retinal nerve fibre layer
      thickness].
AB  - PURPOSE: To assess agreement between one system of time-domain optical coherence
      tomography (OCT) (Stratus) and two systems of fourier-domain OCT (Cirrus and 3D
      OCT-1000) for the measurement of the retinal nerve fibre layer thickness (RNFL).
      METHODS: Fifty eyes from 25 patients with neuro-ophthalmological disorders of the
      afferent visual pathway were included. A triple RNFL thickness OCT examination
      with Stratus, Cirrus and 3D OCT-1000 was performed on both eyes of every patient,
      on the same day and by the same technician. The average RNFL thickness by
      quadrants and clock sectors were compared with the Lin's concordance correlation
      coefficient (CCC) and Bland-Altman plots. RESULTS: The average RNFL thickness,
      the temporal and nasal quadrants and corresponding clock sectors, was higher by
      3D OCT-1000 (mean 90.02 microns), nevertheless, RNFL thickness of the superior
      and inferior quadrants and corresponding clock hours was higher when measured by
      Stratus device. The CCC agreement between Stratus and Cirrus was high (0.820),
      between Stratus and 3D OCT-1000 was moderate (mean 0.573) and between Cirrus and
      3D OCT-1000 was moderate with a mean of 0.564 but too low in the nasal and
      temporal quadrants (0.362 and 0.347 respectively). CONCLUSIONS: The RNFL
      thickness measurements by Stratus, Cirrus and 3D OCT-1000 OCT are not equivalent.
      Although the agreement between Stratus and Cirrus was high, it was too low
      between 3D OCT-1000 and Stratus or Cirrus.

PMID- 23010521
TI  - [Appropriateness of treating glaucoma suspects. Concordancy study with the RAND
      study group].
AB  - OBJECTIVE: The Appropriateness of Treating Glaucoma Suspects Study Group proposes
      to identify which patients suspected of glaucoma are suitable for treatment. Our
      objective is to analyse the concordance between our clinical decisions and this
      Study Group. METHODS: Retrospective study of 77 patients (39 suspects, 38 ocular
      hypertensives). Variables such as age, family history, intraocular pressure, disc
      size, cup-to-disc ratio, central corneal thickness and life expectancy were
      collected.They were scored following the Appropriateness of Treating Glaucoma
      Suspects Scale. Whether there was a consensus to treat or not depended on this
      value. The kappa index was used to measured the concordancy. RESULTS: The kappa
      index was 0.082 (95% confidence interval between -0.11 and 0.27). Total
      concordancy was obtained in 41 patients (63,08%). We decided to treat 25 patients
      (22 of which were not treated by the experts) and not to treat 40 patients (2 of
      which were treated by the experts). In 12 patients there was noconsensus by the
      experts to treat, but we decided to treat 8 of them. CONCLUSIONS: [corrected] The
      concordancy index was low. Others variables such as visual fields and Heidelberg
      Retina Tomography (HRT III) parameters were not collected by the experts but were
      important in our decisions. There are no clinical guidelines on suspects.
      Individualised decisions are still necessary.

PMID- 23010522
TI  - [Atrophy of the retinal nerve fibre layer in multiple sclerosis patients.
      Prospective study with two years follow-up].
AB  - OBJECTIVE: To evaluate the changes over two years in the retinal nerve fibre
      layer (RNFL) of patients with multiple sclerosis (MS). To compare the ability of
      optical coherence tomography (OCT), scanning laser polarimetry (GDx), visual
      evoked potentials (VEP) and visual field examination to detect axonal loss in
      these patients. MATERIAL AND METHODS: Fifty eyes of MS patients without episodes
      or optic neuritis during follow-up were enrolled in this study. All patients
      underwent a complete ophthalmic examination that included visual acuity (VA),
      colour vision, refractive evaluation, visual field examination, OCT, GDx and VEP.
      All the patients were re-evaluated over a period of 12 and 24 months.
      Correlations between parameters were analysed by Pearson's test. RESULTS: There
      were changes in the RNFL thickness in MS patients with a 12 and 24-month follow
      up. Differences between baseline and 2-year evaluation were statistically
      significant (p <= 0.05, t test) in the mean, superior and inferior RNFL thickness
      and macular volume provided by OCT, while no significant differences were found
      using functional parameters (VA, colour vision, visual field and VEP) and GDx.
      The greater differences were obtained in the inferior RNFL thickness (113.67
      frente a 105.39 MUm, p < 0.001). Correlations were observed between structural
      parameters using GDx and TCO. CONCLUSIONS: Progressive axonal loss can be
      detected in the optic nerve of MS patients. Measurements provided by TCO are
      useful tools to evaluate structural abnormalities in the RNFL and changes in
      macular volume, however these changes were not detected using functional tests or
      GDx.

PMID- 23010523
TI  - [Overcorrection secondary to augmented rectus muscle transposition].
AB  - CASE REPORT: Patient with abducens palsy treated with Foster technique after
      injection of botulinum toxin. Exotropia, adduction limitation, face-turn
      inversion and diplopia were observed during the post-operative period. He was
      reinterviened by performing a resection on the medial rectus of the affected and
      toxin was injected into the lateral rectus, as it was technically impossible to
      remove the scleral fixation with an acceptable result. Two years later diplopia
      and increased exotropia reoccurred which again required resection. CONCLUSIONS:
      The Foster technique is our technique of choice in complete abducens palsy,
      however it is important to point out that there could be complications, such as
      overcorrections.

PMID- 23010524
TI  - [Rembrandt's strabismus].

PMID- 23010525
TI  - [Not Available].

PMID- 23010526
TI  - [Not Available].

PMID- 23010527
TI  - [Not Available].

PMID- 23010528
TI  - [Not Available].

PMID- 23010530
TI  - Correlation between the capsaicin test and objective skin measurements in
      evaluating sensitive skin in Chinese females.

PMID- 23010529
TI  - A novel visuospatial priming task for rats with relevance to Tourette syndrome
      and modulation of dopamine levels.
AB  - Individuals with Tourette syndrome (TS) exhibit deficits in inhibitory
      information processing which may reflect impaired neural mechanisms underlying
      symptoms and which can be detected using a negative priming (NP) task. NP is the
      normal reduction of performance when identifying target stimuli that appear where
      non-target stimuli appeared previously. TS subjects exhibit diminished NP and
      their NP levels predict their response to behavioral therapy. Here we review
      relevant literature on this issue and also report a novel rat NP task. In the
      latter, rats respond to target stimuli (continuous light) while ignoring non
      target stimuli (blinking light). Each trial was preceded by a prime in which
      target and non-target stimuli were briefly presented. Performance was challenged
      by shortening prime duration and by administering amphetamine. During the short
      prime challenge, rats exhibited lower accuracy in NP vs. baseline trials,
      indicative of inhibitory information processing. Modulation by amphetamine
      administration indicates that this drug had rate-dependent effects. Evidence is
      provided of individual differences in NP and response to the drug, with priming
      being reduced in high NP rats, while it was increased in low NP subjects. The rat
      NP task represents a novel and suitable tool for investigating the neural bases
      of inhibitory information processing and its dysfunction in TS.

PMID- 23010531
TI  - Monocrotophos pesticide modulates the expression of sexual differentiation genes
      and causes phenotypic feminization in zebrafish (Danio rerio).
AB  - Monocrotophos (MCP) is an organophosphorus pesticide moderately toxic to fish,
      and it has significant estrogenic properties in vivo. In this study, zebrafish
      (Danio rerio) were exposed to 0.001, 0.010, and 0.100 mg/L 40% MCP pesticide in a
      semi-static manner from fertilization to 40 days post-hatching. Histological
      analyses were performed to determine whether sex differentiation in zebrafish was
      affected by MCP, and the mRNA expression levels of genes involved in sexual
      differentiation were quantified by real-time PCR to clarify the possible
      mechanism(s) of action. The results revealed a prominent increase in the
      proportion of females (71%) in the 0.100 mg/L MCP pesticide treatment as well as
      the presence of one intersex individual in each of the groups exposed to 0.001
      and 0.100 mg/L MCP. MCP exposure stimulated forkhead transcription factor gene L2
      (foxl2) expression and suppressed doublesex/mab-3 related transcription factor 1
      (dmrt1) expression, indirectly leading to elevated gonadal aromatase (cyp19a1a)
      gene expression, which should promote phenotypic feminization. In addition, MCP
      treatment increased the transcription of brain aromatase (cyp19a1b), resulting in
      an indirect impact on sexual differentiation. The results from this investigation
      can be used for risk and hazard assessment of MCP pesticide.

PMID- 23010532
TI  - No evidence for genetic association with the let-7 microRNA-binding site or other
      common KRAS variants in risk of endometriosis.
AB  - STUDY QUESTION: Is there a contribution of the minor allele at the KRAS single
      nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to
      endometriosis risk? SUMMARY ANSWER: We found no evidence for association between
      endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN
      ALREADY: The rs61764370 SNP in the 3' untranslated region of the KRAS gene is
      predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA,
      and was recently reported to be at a high frequency (31%) in 132 women of varying
      ancestry with endometriosis compared with frequencies in a database of population
      controls (up to 7.6% depending on ancestry), suggesting a strong effect of this
      KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION: This
      was a case-control study with a total of 11 206 subjects. The study was performed
      between February 2012 and July 2012.   PARTICIPANTS/MATERIALS, SETTINGAND
      METHODS:  We first investigated a possible association between common markers in
      KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194
      surgically confirmed endometriosis cases and 7060 controls of European ancestry.
      Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the
      study were highly correlated with this variant. The rs61764370 and two SNPs
      highly correlated with rs61764370 were then genotyped in 933 endometriosis cases
      and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE
      OF CHANCE: There was no evidence for an association between rs61764370 and
      endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals:
      0.88-1.36). We also found no evidence for an association between the highly
      correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in
      cases and controls were of 0.087-0.091 similar to the population frequency
      reported previously for this variant in controls. Analyses of endometriosis cases
      with revised American Fertility Society stage III/IV disease also showed no
      evidence for an association between these SNPs and endometriosis risk.
      LIMITATIONS AND REASONS FOR CAUTION: The GWA and genotyped data sets were not
      independent since individuals and cases from some families overlap. Controls in
      our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE
      FINDINGS: The key SNP, rs61764370, was genotyped in a subset of samples. Our
      results do not support the suggestion that carrying the minor allele at
      rs61764370 contributes to a significant number of endometriosis cases and
      rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk.
      STUDY FUNDING/COMPETING INTEREST(S): The research was funded by grants from the
      Australian National Health and Medical Research Council and Wellcome Trust. None
      of the authors has competing interests for the study.

PMID- 23010533
TI  - Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen
      samples of infertile couples correlates with recurrent spontaneous abortion.
AB  - STUDY QUESTION: Is the methylation status of the methylenetetrahydrofolate
      reductase (MTHFR) promoter region in semen samples associated with 'recurrent
      spontaneous abortion' (RSA)? SUMMARY ANSWER: MTHFR promoter hypermethylation is
      more frequent in semen samples from RSA couples than in semen samples from
      infertile couples with no history of RSA (NRSA) and affects the whole sperm
      population significantly more often. WHAT IS KNOWN ALREADY: Modifications to the
      MTHFR gene such as polymorphisms and promoter methylations are associated with
      male infertility. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of
      semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between
      2011 and 2012. MATERIALS, SETTING AND METHODS: DNA from the semen samples of RSA,
      NRSA and fertile men were analyzed by methylation-specific PCR amplification
      using primers which anneal to the methylated or unmethylated cytosine
      phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR.
      The specificity of the PCR products was assessed by DNA sequencing. MAIN RESULTS
      AND THE ROLE OF CHANCE: The methylated MTHFR epigenotype (including samples where
      it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA
      men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in
      the whole sperm population in semen samples from 55% of RSA men compared with 8%
      in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis
      was fully concordant with the PCR results and revealed that when MTHFR
      methylation occurred, CpG islands within the promoter region were 100% methylated
      (hypermethylation of MTHFR promoter). LIMITATIONS, REASONS FOR CAUTION: The
      relatively small sample size of RSA infertile couples. WIDER IMPLICATIONS OF THE
      FINDINGS: The hypermethylation of the MTHFR gene promoter should be taken into
      consideration as a novel putative risk factor in RSA etiology. STUDY
      FUNDING/COMPETING INTEREST(S): Our institution has received an FAR research grant
      from the University of Ferrara, Ferrara, Italy. No competing interests declared.

PMID- 23010534
TI  - Tumoral calcinosis in systemic sclerosis.

PMID- 23010535
TI  - Endoplasmic reticulum stress inhibits cell cycle progression via induction of p27
      in melanoma cells.
AB  - The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers
      the unfolded protein response (UPR), a stress signaling pathway. The UPR
      coordinates the induction of ER chaperones with decreased protein synthesis and
      growth arrest in G1 phase of the cell cycle. However, the molecular mechanism
      underlying UPR-induced G1 cell cycle arrest remains largely unknown. Here we
      report that activation of the UPR response by tunicamycin (TM), an ER stress
      inducer, leads to accumulation of p27 and G1 cell cycle arrest in melanoma cells.
      This accumulation of p27 is due to the inhibition on its polyubiquitination and
      subsequent degradation upon TM treatment. Correlated with p27 stabilization, the
      levels of Skp2, an E3 ligase for p27, are decreased in response to TM treatment.
      More importantly, knockdown of p27 greatly reduces TM-induced G1 cell cycle
      arrest. Taken together, these data implicate p27 as a critical mediator of ER
      stress-induced growth arrest.

PMID- 23010536
TI  - Associated clinical characteristics of patients with candidemia among different
      Candida species.
AB  - BACKGROUND: The rising incidence of non-albicans Candida (NAC) infection has been
      associated with a potentially adverse outcome for patients with candidemia.
      However, categorizing various species causing candidemia into a single NAC group
      might lead to inappropriate conclusions due to heterogeneity in species. Thus we
      examined the associated factors among patients with candidemia caused by
      different species. METHODS: This retrospective study was conducted at a tertiary
      medical center in Taiwan from 2006 to 2009. Mortality rate, demographic and
      clinical characteristics, albumin levels, and severity scores of acute illness of
      patients at the onset of candidemia were analyzed. RESULTS: A total of 447
      episodes among 418 patients were included for analysis. The overall 30-day crude
      mortality was 48.2%, with no significant difference between C. albicans and NAC
      candidemia, but apparently C. parapsilosis candidemia was associated with a lower
      mortality rate. Time to positivity for yeast was significantly different between
      species. Compared with infection involving C. albicans, more frequent use of
      total parenteral nutrition, lower Sequential Organ Failure Assessment score and
      higher albumin levels were observed for C. parapsilosis candidemia. CONCLUSION:
      Identifying associated factors for each species may be a more effective approach
      than single NAC grouping. Time to positivity may be a hint for treatment guidance
      in candidemia. More frequent use of total parenteral nutrition and less virulent
      nature were noted for C. parapsilosis candidemia.

PMID- 23010537
TI  - X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature
      review in Taiwanese patients.
AB  - Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder
      characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due
      to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the
      most frequent type, is caused by mutations in the CD40 ligand gene, and is
      regarded as a combined T and B immunodeficiency. We report an 18-year-old male
      who was diagnosed initially with hypogammaglobulinemia in infancy, but developed
      repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and
      bronchiectasis despite regular intravenous immunoglobulin replacement therapy.
      The patient died at age 18 years due to pneumonia and tension pneumothorax.
      Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide
      position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon
      (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L
      protein expression. Sequence analysis in the family confirmed a de novo mutation.
      The second case of 6-month-old male infant presented as Pneumocystis jiroveci
      pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L
      gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a
      carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was
      arranged in the second case.

PMID- 23010538
TI  - Corynebacterium minutissimum infecting pseudomeningocele: a rare case.
AB  - Invasive infections by Corynebacterium minutissimum are rarely documented. The
      significance of laboratory isolation of this bacterium from a sterile specimen
      such as cerebrospinal fluid is difficult to determine as it usually colonizes the
      skin. However, repeated isolation in a clinical setting should be treated
      appropriately. Here we report a first case of infected pseudomeningocele by C.
      minutissimum in an adult woman operated on for falcotentorial psammomatous
      meningioma. The patient was treated successfully with linezolid. 

PMID- 23010539
TI  - Dissemination of multidrug-resistant Acinetobacter baumannii carrying BlaOxA-23
      from hospitals in central Taiwan.
AB  - BACKGROUND: Imipenem-resistant Acinetobacter baumannii (IRAB) poses a great
      threat to healthcare systems. Production of carbapenem-hydrolyzing class D beta
      lactamases (CHDLs) is the major mechanism for imipenem resistance. In this study,
      we found a high prevalence of IRAB carrying a gene encoding CHDL, bla(OxA-23), in
      central Taiwan and elucidated the molecular characteristics and possible
      mechanisms of the spread of these isolates. METHODS: During 2007, we collected
      291 nonrepetitive A baumannii isolates from 10 teaching hospitals in Taiwan. The
      antimicrobial susceptibility of the isolates was determined by agar dilution or
      Etest. The genes encoding carbapenemase and related structure were detected by
      polymerase chain reaction mapping and sequencing, and the clonal relationship of
      the isolates was analyzed by pulsed-field gel electrophoresis. Plasmid
      localization of bla(OxA-23) was determined by extraction of plasmid with
      commercial kit and Southern blot analysis. RESULTS: Among 142 IRAB isolates, 30
      harbored the bla(OxA-23). The prevalence of IRAB with bla(OxA-23) was highest in
      central Taiwan compared to other areas [24.8% (27/109) vs. 1.6% (3/182); p <
      0.001]. These IRAB with bla(OxA-23) were also resistant to other antimicrobial
      agents, except colistin. The PCR methods showed the presence of bla(OxA-51) in
      all isolates. We could exclude clonal spreading due to the diversity of the
      pulsotype. The bla(OxA-23) gene was detected in the plasmids of 6 isolates.
      Tn2006 was present in 22 (73.3%) isolates, and Tn2008, in 6 other isolates
      (26.7%). Two strains had bla(oxa-23)-DeltaATPase but lacked upstream ISAba1.
      CONCLUSION: The high prevalence of bla(OxA-23)-harboring IRAB in central Taiwan
      might be attributed to the transposition event of Tn2006.

PMID- 23010540
TI  - Lipopolysaccharide extracted from Porphyromonas gingivalis induces DNA
      hypermethylation of runt-related transcription factor 2 in human periodontal
      fibroblasts.
AB  - BACKGROUND/PURPOSE: Epigenetic alterations such as DNA methylation and histone
      acetylation are described as changes in the pattern of gene expression not
      involving the DNA sequence. Lipopolysaccharide (LPS) derived from Porphyromonas
      gingivalis has been shown to inhibit osteoblastic cell differentiation. We
      examined whether DNA hypermethylation was involved in the inhibitory effect of
      LPS on osteoblastic differentiation of fibroblasts derived from human periodontal
      ligament (HPDL). METHODS: The HPDL cells were incubated with LPS derived from P.
      gingivalis at a concentration of 10 MUg/ml for 24 h. The cells were treated with
      DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5Aza). Untreated cells
      were used as a control. Cell viability was determined using cell proliferation
      reagent. DNA methyltransferase (DNMT1) and runt-related transcription factor 2
      (RUNX2) mRNAs were evaluated by quantitative polymerase chain reaction (RT-PCR).
      Analysis of RUNX2 DNA methylation was performed using quantitative methylation
      specific PCR. RESULTS: The expression level of RUNX2 was significantly lower in
      the cells stimulated with LPS than the controls. The presence of 5Aza increased
      the expression of RUNX2 in cells stimulated with LPS. The expression levels of
      DNMT1 mRNA in the cells stimulated with LPS were significantly higher than in the
      control. The presence of 5Aza completely abolished the upregulated expression of
      DNMT1 in cells stimulated with LPS. The methylation of DNA at 0.1 kb and -1.9 kb
      in the cells stimulated with LPS was significantly higher than the control.
      CONCLUSION: The results indicate that DNA hypermethylation may be involved in the
      inhibitory effect of LPS on osteoblastic differentiation in HPDL.

PMID- 23010541
TI  - Rapamycin-induced modulation of HIV gene transcription attenuates progression of
      HIVAN.
AB  - HIV-associated nephropathy (HIVAN) is the manifestation of HIV gene expression by
      kidney cells in the presence of specific host factors. Recently, rapamycin
      (sirolimus) has been demonstrated to modulate the progression of HIVAN. We
      hypothesized that rapamycin would modulate the progression of HIVAN by
      attenuating HIV gene expression. To test our hypothesis, three weeks old Tg26
      mice (n=6) were administered either vehicle or rapamycin (5 mg/kg, every other
      day, intraperitoneal) for eight weeks. At the end of the experimental period, the
      kidneys were harvested. In in vitro studies, human podocytes were transduced with
      either HIV-1 (NL4-3) or empty vector (EV), followed by treatment with either
      vehicle or rapamycin. Total RNA and proteins were extracted from renal
      tissues/cellular lysates and HIV gene transcription/translation was measured by
      real time PCR and Western blotting studies. Renal histological slides were graded
      for glomerular sclerosis and tubular dilatation with microcyst formation.
      Rapamycin attenuated both glomerular and tubular lesions in Tg26 mice. Rapamycin
      decreased transcription of HIV genes both in renal tissues as well as in HIV-1
      transduced podocytes. Our data strongly indicate that HIV-1 long terminal repeat
      mediated transcriptional activity was targeted by rapamycin. Rapamycin enhanced
      podocyte NF-kappaB and CREB activities but then it decreased AP-1 binding
      activity. Since expression of HIV genes by kidney cells has been demonstrated to
      be the key factor in the development HIVAN, it appears that rapamycin-induced
      altered transcription of HIV genes might have partly contributed to its disease
      modulating effects.

PMID- 23010542
TI  - Ecological status assessment and response of benthic communities to environmental
      variability: the Valli di Comacchio (Italy) as a study case.
AB  - The Valli di Comacchio is one of most representative choked (not influenced by
      the tidal regime) lagoons in the Mediterranean and Europe. We compared the
      ecological status (ES) classification (sensu European Water Framework Directive,
      2000/60/EC) of the Valli obtained through supporting physicochemical elements and
      biotic indices. The variability of water parameters was investigated through 1997
      2002 at 4 permanent sampling stations. During the six years of investigation,
      macrobenthic data were collected to identify the response of several biological
      indices (taxonomic, functional and ecological). ES classification through
      supporting physicochemical elements resulted in discordant patterns. Nor
      taxonomic neither functional measures were able to add more information than that
      given by univariate biodiversity measures. Gaps and bias of the indices used were
      identified. Due to the absence of well defined environmental gradients, taxonomic
      and functional measures loose most of their usefulnesses. ES classification
      through ecological indices (M-AMBI and BITS) resulted in quite a concordant
      pattern, although BITS underestimated ES when there was a strong dominance of one
      opportunist family in the benthic community.

PMID- 23010543
TI  - Evaluation of olfactory dysfunction in neurodegenerative diseases.
AB  - It is known that the olfactory dysfunction is involved in various neurological
      diseases, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis,
      Huntington's disease and motor neuron disease. In particular, the ability to
      identify and discriminate the odors, as well as the odor threshold, can be
      altered in these disorders. These changes often occur as early manifestation of
      the pathology and they are not always diagnosed on time. The aim of this review
      is to summarize the major neurological diseases which are preceded or accompanied
      by olfactory dysfunction. In addition, new instrumental approaches, such as
      psychophysical testing, olfactory event-related potentials (OERPs) and functional
      magnetic resonance imaging (fMRI) measurements, supported by olfactometer for the
      stimuli delivery, and their combination in evaluation of olfactory function will
      be discussed. In particular, OERPs and fMRI might to be good candidates to become
      useful additional tools in clinical protocols for early diagnosis of neurological
      diseases.

PMID- 23010546
TI  - ZVI-Clay remediation of a chlorinated solvent source zone, Skuldelev, Denmark: 1.
      Site description and contaminant source mass reduction.
AB  - Field investigations on the effects of ZVI-Clay soil mixing were conducted at a
      small DNAPL source zone with PCE as the parent compound. In a one-year monitoring
      program, soil samples were collected at three horizontal sampling planes (2.5,
      5.0 and 7.5m bgs.). PCE was found to have a pseudo first-order degradation half
      life of 47days resulting in more than 99% depletion of the source mass after one
      year. The main degradation product was ethene, while only low concentrations of
      the primarily biotic sequential degradation products (cDCE, VC) were detected.
      The soil mixing resulted in more homogeneous vertical conditions, while the
      horizontal homogenization was very limited. Iron was delivered in the full
      targeted depth with an average iron enrichment of 3.1%, and an average decline in
      the oxidation-reduction potential of more than 500mV. Due to the applied top-down
      addition of ZVI, the iron content decreased from 4.6% to 2.1% on average over a
      depth of 5m; hence, there is a potential for optimization of the delivery method.
      Most in situ technologies are limited by subsurface heterogeneities, whereby the
      successful dispersion of geological units and contaminants holds great promise
      for remediation of DNAPL source zones with ZVI-Clay soil mixing.

PMID- 23010545
TI  - Perineural tumor spread - Interconnection between spinal and cranial nerves.
AB  - The secondary neoplastic involvement of the cervical plexus in patients with head
      and neck malignancies is extremely rare. MR examination of the neck revealed the
      diffuse neoplastic infiltration of the right C2 root, in a 57-year-old patient
      with several months long pain in the right ear region and a history of the tongue
      squamous cell carcinoma. Associated perineural tumor spread and consequent distal
      involvement of great auricular nerve and vagus nerve were evident. Best of our
      knowledge, this is the first reported involvement of the cervical plexus in
      patients with head and neck cancers, associated with the clearly documented
      interconnection between the cervical plexus and cranial nerves via great
      auricular nerve.

PMID- 23010547
TI  - ZVI-Clay remediation of a chlorinated solvent source zone, Skuldelev, Denmark: 2.
      Groundwater contaminant mass discharge reduction.
AB  - The impact of source mass depletion on the down-gradient contaminant mass
      discharge was monitored for a 19-month period as a part of a field demonstration
      of the ZVI-Clay soil mixing remediation technology. Groundwater samples were
      collected from conventional monitoring wells (120 samples) and a dense network of
      multilevel samplers (640 samples). The hydraulic gradient and conductivity were
      determined. Depletion of the contaminant source is described in the companion
      paper (Fjordboge et al., 2012). Field data showed four distinct phases for PCE
      mass discharge: (1) baseline conditions, (2) initial rapid reduction, (3)
      temporary increase, and (4) slow long-term reduction. Numerical modeling was
      utilized to develop a conceptual understanding of the four phases and to identify
      the governing processes. The initial rapid reduction of mass discharge was a
      result of the changed hydraulic properties in the source zone after soil mixing.
      The subsequent phases depended on the changed accessibility of the contaminant
      mass after mixing, the rate of source depletion, and the concentration gradient
      at the boundaries of the mixed source zone. Overall, ZVI-Clay soil mixing
      resulted in a significant down-gradient contaminant mass discharge reduction
      (76%) for the parent compound (PCE), while the overall reduction of chlorinated
      ethenes was smaller (21%).

PMID- 23010548
TI  - Laboratory-scale experiments and numerical modeling of cosolvent flushing of
      multi-component NAPLs in saturated porous media.
AB  - This study examines the mechanistic processes governing multiphase flow of a
      water-cosolvent-NAPL system in saturated porous media. Laboratory batch and
      column flushing experiments were conducted to determine the equilibrium
      properties of pure NAPL and synthetically prepared NAPL mixtures as well as NAPL
      recovery mechanisms for different water-ethanol contents. The effect of contact
      time was investigated by considering different steady and intermittent flow
      velocities. A modified version of multiphase flow simulator (UTCHEM) was used to
      compare the multiphase model simulations with the column experiment results. The
      effect of employing different grid geometries (1D, 2D, 3D), heterogeneity and
      different initial NAPL saturation configurations was also examined in the model.
      It is shown that the change in velocity affects the mass transfer rate between
      phases as well as the ultimate NAPL recovery percentage. The experiments with low
      flow rate flushing of pure NAPL and the 3D UTCHEM simulations gave similar
      effluent concentrations and NAPL cumulative recoveries. Model simulations over
      estimated NAPL recovery for high specific discharges and rate-limited mass
      transfer, suggesting a constant mass transfer coefficient for the entire flushing
      experiment may not be valid. When multi-component NAPLs are present, the
      dissolution rate of individual organic compounds (namely, toluene and benzene)
      into the ethanol-water flushing solution is found not to correlate with their
      equilibrium solubility values.

PMID- 23010549
TI  - [Not Available].

PMID- 23010550
TI  - [Not Available].

PMID- 23010551
TI  - [Not Available].

PMID- 23010552
TI  - [Not Available].

PMID- 23010553
TI  - Functional development of the olfactory system in zebrafish.
AB  - The olfactory system has become a popular model to study the function of neuronal
      circuits and the molecular and cellular mechanisms underlying the development of
      neurons and their connections. An excellent model to combine studies of function
      and development is the zebrafish because it not only permits sophisticated
      molecular and genetic analyses of development, but also functional measurements
      of neuronal activity patterns in the intact brain. This article reviews insights
      into the functional development of the olfactory system that have been obtained
      in zebrafish. The focus is on the specification of olfactory sensory neurons
      (OSNs), the mechanisms controlling odorant receptor expression and OSN identity,
      the pathfinding of OSN axons towards target glomeruli in the olfactory bulb (OB),
      the development of glomeruli and functional topographic maps in the OB, and the
      development of inhibitory interneurons in the OB.

PMID- 23010554
TI  - Comparison of whole-blood interferon-gamma assay and flow cytometry for the
      detection of tuberculosis infection.
AB  - OBJECTIVE: Limited data exist about the performance of the intracellular cytokine
      flow cytometry (ICCFC) with respect to that of the commercial interferon-gamma
      release assay for the detection of tuberculosis (TB) infection. Here, we compared
      the diagnostic accuracy of an ICCFC with that of the QuantiFERON-TB Gold In-Tube
      (QFT-IT) test for the detection of TB in a clinical setting. METHODS: Eighty-nine
      patients suspected of having TB were prospectively included. Both the QFT-IT test
      and ICCFC were performed for all subjects (TB [n = 65] and non-TB [n = 24]). Ten
      healthy controls who tested negative by QFT-IT were also assessed by ICCFC.
      RESULTS: The sensitivity of the ICCFC was significantly superior to that of the
      QFT-IT test (91% vs. 78%, p = 0.021). The clinical characteristics of patients in
      whom the ICCFC exhibited superior sensitivity compared to the QFT-IT test
      included advanced age, lymphocytopenia, hypoalbuminemia, increased C-reactive
      protein level, a positive acid-fast bacilli smear of respiratory specimens, and
      radiographically more extensive disease. CONCLUSIONS: ICCFC might be a preferable
      technique for the detection of TB infection, particularly in patients with
      conditions associated with impaired performance of the QFT-IT test.

PMID- 23010555
TI  - Sleep disturbances and low psychological well-being are associated with an
      increased risk of autoimmune diabetes in adults. Results from the Nord-Trondelag
      Health Study.
AB  - AIMS: To investigate whether sleep disturbances and low psychological well-being
      are associated with an increased risk of autoimmune diabetes in adults (including
      LADA and type 1 diabetes) and type 2 diabetes. METHODS: We used data from the
      Norwegian HUNT Study (n = 53,394) and estimated the risk of developing autoimmune
      diabetes in adults (n = 138) and type 2 diabetes (n = 1895) between 1984 and 2008
      in relation to baseline self-reported psychological well-being and sleep
      problems. RESULTS: Sleep disturbances and low psychological well-being were
      associated with an increased risk of autoimmune diabetes (hazard ratio 1.84, 95%
      confidence interval 1.10-3.09), primarily linked to poor sleep in men (1.83, 1.05
      3.20) and low well-being in women (2.50, 1.03-6.54). Similar associations were
      seen with type 2 diabetes in relation to sleep problems (1.25, 1.08-1.44) in men
      and low well-being (1.34, 1.16-1.54), in both men and women. In autoimmune
      diabetes, these factors were associated with lower anti-GAD levels (177 vs. 306
      WHO units/ml, p = 0.04). CONCLUSIONS: Our findings indicate that psychosocial
      factors influence the risk of autoimmune diabetes in adults, possibly through
      mechanisms related to insulin resistance. This supports the notion that the
      aetiology of autoimmune diabetes with adult onset in some respects is similar to
      that of type 2 diabetes.

PMID- 23010556
TI  - Tianjin Gestational Diabetes Mellitus Prevention Program: study design, methods,
      and 1-year interim report on the feasibility of lifestyle intervention program.
AB  - OBJECTIVE: To assess whether lifestyle intervention can reduce type 2 diabetes
      risk in women with prior GDM in the Tianjin Gestational Diabetes Mellitus (GDM)
      Prevention Program. METHODS: 1180 women who were diagnosed with GDM from 2005 to
      2009 were randomly assigned to either a lifestyle intervention (n=586) or a
      control group (n=594). Major elements of the intervention include six face-to
      face meetings with study dietitians in the first year, and two additional
      sessions and two telephone calls in second year. RESULTS: During the first year,
      average body weight loss in the first 404 subjects was 1.40 kg (2.1%) in the
      intervention group vs 0.21 kg (0.3%) in the control group (P=0.001), and the
      decrease was more significant among baseline overweight women (body bass index
      [BMI]>=24 kg/m2) in the intervention (2.91 kg/4.2%) compared with that in the
      control group (0.51 kg/0.7%) (P<0.001). In addition, women in the intervention
      group, compared with those in the control group, have decreased BMI, body fat,
      waist circumference, and plasma insulin levels, and have improved behaviors
      including increased leisure time activity and dietary fiber intake and decreased
      sedentary time and fat consumptions. CONCLUSION: The interim results support the
      efficacy and feasibility of the lifestyle intervention program.

PMID- 23010557
TI  - Determining the optimal cutoff points for waist circumference and body mass index
      for identification of metabolic abnormalities and metabolic syndrome in urban
      Thai population.
AB  - This study describes the prevalence and optimal waist circumference (WC) and body
      mass index (BMI) cutoff point for metabolic abnormalities and metabolic syndrome
      (MS) from urban Thai population. The optimal BMI/WC cutoff has been used for
      identifying and evaluating metabolic abnormalities for screening individuals
      having risk factor of MS.

PMID- 23010558
TI  - The glucokinase activator AZD6370 decreases fasting and postprandial glucose in
      type 2 diabetes mellitus patients with effects influenced by dosing regimen and
      food.
AB  - AIMS: To investigate the pharmacodynamics, pharmacokinetics and safety of the
      glucokinase activator AZD6370 after 1 day of administration under fed and fasted
      conditions in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a
      two-part study. In Part A, patients received a single oral dose of AZD6370 (20,
      60 or 180 mg) or placebo in the fasted or fed states (both n=8). In Part B,
      patients (n=8) received placebo and a total dose of AZD6370 180 mg given in one,
      two or four divided doses. Plasma glucose, insulin and C-peptide changes versus
      placebo were assessed. RESULTS: AZD6370 provided dose-dependent reductions in
      plasma glucose of up to 30% versus placebo in both fasted and fed patients
      (p<0.001 at 60 and 180 mg doses). Insulin secretion increased with dose, but
      absolute increases were relatively small in the fasted versus fed state (0-4 h).
      Dosing AZD6370 twice or four-times over 1 day gave a smoother 24-h glucose
      profile than single-dose. AZD6370 was rapidly absorbed. Pharmacokinetics of
      AZD6370 were dose-independent and unaffected by food. AZD6370 was generally well
      tolerated. CONCLUSIONS: AZD6370 produced dose-dependent glucose reductions and
      increased glucose-stimulated insulin secretion in patients with T2DM.

PMID- 23010559
TI  - Risk scores based on self-reported or available clinical data to detect
      undiagnosed type 2 diabetes: a systematic review.
AB  - OBJECTIVE: To systematically review published primary research on the development
      or validation of risk scores that require only self-reported or available
      clinical data to identify undiagnosed Type 2 Diabetes Mellitus (T2DM). METHODS: A
      systematic literature search of Medline and EMBASE was conducted until January
      2011. Studies focusing on the development or validation of risk scores to
      identify undiagnosed T2DM were included. Risk scores to predict future risk of
      T2DM were excluded. RESULTS: Thirty-one studies were included; 17 developed a new
      risk score, 14 validated existing scores. Twenty-six studies were conducted in
      high-income countries. Age and measures of body mass/fat distribution were the
      most commonly used predictor variables. Studies developing new scores performed
      better than validation studies, with 11 reporting an AUC of >0.80 compared to one
      validation study. Fourteen validation studies reported sensitivities of <80%. The
      performance of scores did not differ by the number of variables included or the
      country setting. CONCLUSIONS: There is a proliferation of newly developed risk
      scores using similar variables, which sometimes perform poorly upon external
      validation. Future research should explore the recalibration, validation and
      applicability of existing scores to other settings, particularly in low/middle
      income countries, and on the utility of scores to improve diabetes-related
      outcomes.

PMID- 23010560
TI  - Reduction in metabolic syndrome among obese young men is associated with exercise
      induced body composition changes during military service.
AB  - AIMS: A population-based study of 1046 young Finnish men was performed to
      evaluate whether body composition changes observed during military service are
      associated with a reduction in prevalence of metabolic syndrome (MetS), and
      whether the effect is body mass index (BMI)-dependent. METHODS: A prospective
      study of 1046 men (mean age 19.2 years, SD 1.0), with follow-up during 6-12
      months of military service in northern Finland. Anthropometry, body composition,
      biochemical measurements and physical fitness were assessed at baseline and
      follow-up. MetS was defined using the International Diabetes Federations (IDF)
      criterion, continuous MetS Z-score calculated, and changes evaluated in BMI
      categories. RESULTS: Prevalence of MetS at baseline and follow-up was 6.1% and
      3.6%, respectively (p < 0.001). Prevalence of MetS decreased by 40% (p < 0.001)
      among the obese young men (BMI >= 30 kg/m(2)). Reduction in the MetS Z-score was
      mainly attributable to weight loss and reduced fat mass (p < 0.001) and
      improvement in physical fitness (muscle fitness index, p = 0.016). CONCLUSIONS:
      Beneficial exercise-induced changes in body composition significantly reduced the
      prevalence of MetS among young, obese men. Our findings support the efficacy of
      increased physical activity for prevention of early-onset cardiovascular disease,
      particularly among overweight and obese young men.

PMID- 23010561
TI  - A meta-analysis of serious adverse events reported with exenatide and
      liraglutide: acute pancreatitis and cancer.
AB  - AIMS: The association between GLP-1 agonists, acute pancreatitis (AP), any cancer
      and thyroid cancer is discussed. This meta-analysis was aimed at evaluating the
      risk of those serious adverse events associated with GLP-1 agonists in patients
      with type 2 diabetes. METHODS: Medline, EMBASE, Cochrane Library and
      clinicaltrials.gov were searched in order to identify longitudinal studies
      evaluating exenatide or liraglutide use and reporting data on AP or cancer. Odds
      ratios (ORs) were pooled using a random-effects model. I(2) statistics assessed
      heterogeneity. RESULTS: Twenty-five studies were included. Neither exenatide (OR
      0.84 [95% CI 0.58-1.22], I(2) = 30%) nor liraglutide (OR 0.97 [95% CI 0.21-4.39],
      I(2) = 0%) were associated with an increased risk of AP, independent of baseline
      comparator. The pooled OR for cancer associated with exenatide was 0.86 (95% CI
      0.29, 2.60, I(2) = 0%) and for liraglutide was 1.35 (95% CI 0.70, 2.59, I(2) =
      0%). Liraglutide was not associated with an increased risk for thyroid cancer (OR
      1.54 [95% CI 0.40-6.02], I(2) = 0%). For exenatide, no thyroid malignancies were
      reported. CONCLUSIONS: Current available published evidence is insufficient to
      support an increased risk of AP or cancer associated with GLP-1 agonists. These
      rare and long-term adverse events deserve properly monitoring in future studies
      evaluating GLP-1 agonists.

PMID- 23010562
TI  - Subtypes of developmental dyslexia: testing the predictions of the dual-route and
      connectionist frameworks.
AB  - We investigated the phonological and surface subtypes of developmental dyslexia
      in light of competing predictions made by two computational models of single word
      reading, the Dual-Route Cascaded Model (DRC; Coltheart, Rastle, Perry, Langdon, &
      Ziegler, 2001) and Harm and Seidenberg's connectionist model (HS model; Harm &
      Seidenberg, 1999). The regression-outlier procedure was applied to a large sample
      to identify children with disproportionately poor phonological coding skills
      (phonological dyslexia) or disproportionately poor orthographic coding skills
      (surface dyslexia). Consistent with the predictions of the HS model, children
      with "pure" phonological dyslexia, who did not have orthographic deficits, had
      milder phonological impairments than children with "relative" phonological
      dyslexia, who did have secondary orthographic deficits. In addition, pure cases
      of dyslexia were more common among older children. Consistent with the
      predictions of the DRC model, surface dyslexia was not well conceptualized as a
      reading delay; both phonological and surface dyslexia were associated with
      patterns of developmental deviance. In addition, some results were problematic
      for both models. We identified a small number of individuals with severe
      phonological dyslexia, relatively intact orthographic coding skills, and very
      poor real word reading. Further, a subset of controls could read normally despite
      impaired orthographic coding. The findings are discussed in terms of improvements
      to both models that might help better account for all cases of developmental
      dyslexia.

PMID- 23010563
TI  - Probiotics in transition.
AB  - Despite the hyperbole often linked with a popular research field, the scientific
      rationale for probiotics is sound. The probiotic concept is not new but is
      undergoing transition as knowledge of the gut microbiota in health and disease
      becomes translated to the clinic. Operationally, a probiotic represents a mimic
      of and/or supplement to the normal gut microbiota. Much confusion has arisen
      among consumers because of media misportrayals of probiotics as all being the
      same. However, with clarification of the molecular basis of host-microbe
      interactions, the selection criteria for probiotics and the delineation of their
      distinct mechanisms of action are improving. Most probiotics are from the genus
      Lactobacillus or Bifidobacterium; this is likely to change and diversify.
      Similarly, the development of new therapeutic strategies, such as the development
      of phagebiotics, psychobiotics, and genetically modified pharmabiotics, is poised
      to become a therapeutic reality.

PMID- 23010564
TI  - Synergistic combination dry powders for inhaled antimicrobial therapy:
      formulation, characterization and in vitro evaluation.
AB  - In combination antimicrobial therapy, the desired outcome is to broaden the
      antimicrobial spectrum and to achieve a possible synergistic effect. However,
      adverse antagonistic species may also emerge from such combinations, leading to
      treatment failure with serious consequences. It is therefore imperative to screen
      the drug candidates for compatibility and possible antagonistic interactions. The
      aim of this work was to develop a novel synergistic dry powder inhaler (DPI)
      formulation for antimicrobial combination therapy via the pulmonary route. Binary
      (ciprofloxacin hydrochloride and gatifloxacin hydrochloride, SD-CIP/GAT) and
      ternary (ciprofloxacin hydrochloride, gatifloxacin hydrochloride, and lysozyme,
      SD-CIP/GAT/LYS) combinations were prepared via spray-drying on a BUCHI(r) Nano
      Spray Dryer B-90. The powder morphologies were spherical with a slightly
      corrugated surface and all within the respirable size range. The powders yielded
      fine particle fractions (of the loaded dose) of over 40% when dispersed using an
      Aerolizer(r) at 60 L/min. Time-kill studies carried out against the respiratory
      tract infection-causing bacteria Pseudomonas aeruginosa, Staphylococcus aureus,
      Klebsiella pneumonia, and Acinetobacter baumannii at 1 * the minimum inhibitory
      concentration (MIC) over 24h revealed no antagonistic behavior for both the
      binary and ternary combinations. While the interactions were generally found to
      be indifferent, a favorable synergistic effect was detected in the dual
      combination (SD-CIP/GAT) when it was tested against P. aeruginosa bacteria.

PMID- 23010565
TI  - Liquid crystalline phase nanodispersions enable skin delivery of siRNA.
AB  - The ability of small interfering RNAs (siRNAs) to potently but reversibly silence
      genes in vivo has made them particularly well suited as a new class of drugs that
      interfere with disease-causing or disease-promoting genes. However, the largest
      remaining hurdle for the widespread use of this technology in skin is the lack of
      an effective delivery system. The aim of the present study was to evaluate
      nanodispersed systems in liquid crystalline phases that deliver siRNA into the
      skin. The proposed systems present important properties for the delivery of
      macromolecules in a biological medium, as they are formed by substances that have
      absorption-enhancing and fusogenic effects; additionally, they facilitate
      entrapment by cellular membranes due to their nano-scale structure. The cationic
      polymer polyethylenimine (PEI) or the cationic lipid oleylamine (OAM) were added
      to monoolein (MO)-based systems in different concentrations, and after dispersion
      in aqueous medium, liquid crystalline phase nanodispersions were obtained and
      characterized by their physicochemical properties. Then, in vitro penetration
      studies using diffusion cell and pig ear skin were carried out to evaluate the
      effect of the nanodispersions on the skin penetration of siRNA; based on these
      results, the nanodispersions containing MO/OA/PEI/aqueous phase (8:2:5:85,
      w/w/w/w) and MO/OA/OAM/aqueous phase (8:2:2:88, w/w/w/w) were selected. These
      systems were investigated in vivo for skin penetration, skin irritation, and the
      ability to knockdown glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein
      levels in animal models. The results showed that the studied nanodispersions may
      represent a promising new non-viral vehicle and can be considered highly
      advantageous in the treatment of skin disorders; they were effective in
      optimizing the skin penetration of siRNA and reducing the levels of the model
      protein GAPDH without causing skin irritation.

PMID- 23010566
TI  - Iodinated nano-emulsions as contrast agents for preclinical X-ray imaging: Impact
      of the free surfactants on the pharmacokinetics.
AB  - This study presents new important aspects in the design of contrast agents for X
      ray preclinical imaging. The first one is a new simple formulation of long
      circulating contrast agents, formulated from a commercial iodinated oil, and
      resulting in CT contrast agents containing more than twice the iodine
      concentration commercial contrast agents. The second point is a methodological
      aspect, utilizing tangential filtration for reducing the residual surfactants in
      the bulk phase and serving as well for concentrating droplets (and iodine) in the
      suspension. The last point is a more general aspect regarding the influence of
      the free surfactant on the pharmacokinetics and biodistribution of the nano
      emulsion droplets on mice. We showed that cross-flow filtration is efficient for
      concentrating the droplets and reducing the concentration of free surfactant from
      10wt.% to 1wt.%, without any changes in the nano-emulsion droplet morphologies or
      surface properties. We also showed that the presence of free surfactant has a
      significant impact on the elimination way of the nano-emulsion droplets, shared
      between liver and kidneys. The purified nano-emulsions are preferentially
      eliminated by the kidneys in contrast to raw nano-emulsions, predominantly
      eliminated by the liver. In practice, for two similar suspensions, half-life
      decreases from 4.1+/-1.10h to 2.5+/-0.77h before and after purification. Since
      the design and development of long circulating systems are critical in numerous
      domains, and not for preclinical CT imaging, this study presents important
      results in that field, taken under a formulation and technical point of view.

PMID- 23010567
TI  - Fronto-limbic microstructure and structural connectivity in remission from major
      depression.
AB  - Previous research has suggested that abnormalities within the amygdala and
      prefrontal cortex (PFC) may underlie major depressive disorder (MDD). The
      contribution of microstructural alterations within these regions in adult MDD is
      still equivocal. Therefore, seventeen middle-aged medication-free remitted MDD
      patients and 21 matched never-depressed control subjects underwent structural
      magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Despite
      comparable amygdala volumes, remitted MDD patients revealed decreased mean
      diffusivity (MD) and increased fractional anisotropy (FA) within the left
      amygdala, which may be interpreted as greater cell density and increased number
      of fibers, respectively. This last notion was supported by probabilistic
      tractography results, which revealed increased connectivity from the left
      amygdala to the hippocampus, the cerebellum and the brain stem. Further, altered
      microstructure as indicated by increased MD possibly reflecting decreased cell
      density within the medial PFC (mPFC) was found. Taken together, the current DTI
      study shows that abnormal microstructure and connectivity of the amygdala and
      mPFC might be key factors in the pathophysiology of MDD that may account for
      functional changes.

PMID- 23010568
TI  - Evaluation of an indirect ELISA using a tachyzoite surface antigen SAG1 for
      diagnosis of Toxoplasma gondii infection in cats.
AB  - Toxoplasma gondii infection is very common in cats throughout the world. Most
      cats are subclinically infected and potentially fatal clinical disease occurs in
      some of them. The aim of this study is to develop an indirect enzyme linked
      immunosorbent assay (ELISA) test using an affinity purified tachyzoite surface
      antigen (SAG1) to detect T. gondii infection in cats. Six sero-negative kittens
      were used in this study; four kittens received 10(4) T. gondii tachyzoites of NED
      strain (type III) and the remaining two were used as uninfected controls. Serum
      samples were collected within 41 days and were evaluated for anti-T. gondii
      antibodies using indirect fluorescent antibody test (IFAT) and ELISA method. IgG
      antibodies were detectable at least from eight days after tachyzoites inoculation
      and an increasing pattern in both serum ELISA indices (SIns) and IFAT titers were
      detected. SIns were significantly different in sera of cats presenting different
      IFAT titers. In order to evaluate the performance of ELISA to detect anti-T.
      gondii antibodies of naturally infected cats, serum samples were also collected
      from household and stray cats and evaluated in the same way. IFAT was regarded as
      the standard test and sensitivity and specificity of the ELISA to detect the
      infection in naturally infected kittens were analyzed using two-graph receiver
      operating characteristic (TG-ROC) analysis. An area under curve (AUC) of 0.996
      revealed the test as a highly accurate test with relative sensitivity and
      specificity of 100% and 96% for a cut-off value of 0.10 for SIn.

PMID- 23010569
TI  - Anti-Acanthamoebic properties of resveratrol and demethoxycurcumin.
AB  - Acanthamoeba is an opportunist protist pathogen that is known to infect the
      cornea to produce eye keratitis and the central nervous system to produce fatal
      granulomatous encephalitis. Early diagnosis, followed by aggressive treatment
      using a combination of drugs is a prerequisite in successful treatment but even
      then, prognosis remains poor due to lack of effective drugs. The overall aim of
      the present study was to determine the anti-Acanthamoebic potential of natural
      compounds, resveratrol and curcuminoids. Adhesion and cytotoxicity assays were
      performed using primary human brain microvascular endothelial cells, which
      constitute the blood-brain barrier. Pre-exposure of organisms to 100 MUg
      resveratrol and demethoxy curcumin prevented amoeba binding by 57% and 73%,
      respectively, while cytotoxicity of host cells was inhibited by 86%. In an assay
      for viability of amoebae in the absence of host cells, resveratrol and de-methoxy
      curcumin exhibited significant amoebicidal effects (23% and 25%, respectively) at
      100 MUg concentrations (P<0.01). Neither resveratrol nor demethoxycurcumin had
      any effect on the proteolytic activities of Acanthamoeba castellanii. Of both
      compounds, resveratrol is of most interest for further investigation, because of
      the selective toxicity of resveratrol on A. castellanii but not the human brain
      microvascular endothelial cells.

PMID- 23010570
TI  - An investigation to determine if a single validated density-elasticity
      relationship can be used for subject specific finite element analyses of human
      long bones.
AB  - Subject-specific FE-models of human long bones have to predict mechanical
      parameters with sufficient accuracy to be applicable in a clinical setting. One
      of the main aspects in subject-specific FE-models of bones regarding accuracy is
      the modeling of the material inhomogeneity. The goal of this study was therefore
      to develop FE-models of human femurs and investigate if a single validated
      density-elasticity relationship can be used for subject specific finite element
      analyses of human long bones, when the task is to predict the bone's mechanical
      response to load. To this aim, 23 human cadaver femurs were tested in axial
      compression with a load of 1000 N. Strains, local displacements, and axial bone
      stiffness were determined. Subject-specific FE-models were developed for each
      bone based on quantitative CT-scans. Three different density-elasticity
      relationships were retrieved from the literature, and were implemented in the FE
      models. The predicted mechanical values depended largely on the used equation.
      The most reasonable equation showed a mean error of -11% in strain prediction, a
      mean error of -23% in local displacement prediction, and a mean error of +23% in
      axial stiffness prediction. The scatter of the predictions was very low in all
      three categories of measurements with a 1.96 standard deviation of about 30% to
      the mean errors. In conclusion, a framework for subject-specific FE-models was
      developed that was able to predict surface strains and bone deformation with good
      accuracy by using a single density-elasticity relationship. However, it was also
      found that the most appropriate density-elasticity relationship was specimen
      specific.

PMID- 23010572
TI  - Characteristics of women visiting an infertility clinic and their interest in
      preimplantation sex selection in the north of Jordan.
AB  - OBJECTIVES: To describe the characteristics of women attending a fertility clinic
      for infertility treatment and to determine their interest in the use of
      preconception sex selection and its associated factors. METHODS: A cross
      sectional study was conducted among women who presented to the fertility clinic
      in the IVF center for infertility treatment. A total of 335 women were included
      in the study and interviewed using the study questionnaire, which included
      information on patients' demographics, obstetric and infertility history, child
      gender preference, and interest in preconception sex selection. RESULTS: A total
      of 155 (46.3%) women had primary infertility and 180 (53.7%) had secondary
      infertility. While preference for a boy was reported by 50 (14.9%) participants
      and preference for a girl was reported by seven (2.1%), the majority of women
      (83.0%) had no preference for gender. A total of 59 (17.6%) women showed an
      interest in using preconception sex selection. In the multivariate analysis,
      women who preferred a boy were more likely to be interested in preconception sex
      selection (OR=3.52) compared to women who had no preference for gender. Trying to
      conceive for >=2 years was associated with an 80% increase in the odds of being
      interested in preconception sex selection. CONCLUSIONS: The majority of women
      (83.0%) had no gender preference. Less than one fifth of women (17.6%) showed an
      interest in using assisted method for sex selection. Preference for a boy and
      trying to conceive for >=2 years were significantly associated with increased
      odds of being interested in using preconception sex selection.

PMID- 23010571
TI  - A disintegrin-like and metalloprotease domain containing thrombospondin type 1
      motif-like 5 (ADAMTSL5) is a novel fibrillin-1-, fibrillin-2-, and heparin
      binding member of the ADAMTS superfamily containing a netrin-like module.
AB  - ADAMTS-like proteins are related to ADAMTS metalloproteases by their similarity
      to ADAMTS ancillary domains. Here, we have characterized ADAMTSL5, a novel member
      of the superfamily with a unique modular organization that includes a single C
      terminal netrin-like (NTR) module. Alternative splicing of ADAMTSL5 at its 5' end
      generates two transcripts that encode different signal peptides, but the same
      mature protein. These transcripts differ in their translational efficiency.
      Recombinant ADAMTSL5 is a secreted, N-glycosylated 60kDa glycoprotein located in
      the subcellular matrix, on the cell-surface, and in the medium of transfected
      cells. RT-PCR and western blot analysis of adult mouse tissues showed broad
      expression. Western blot analysis suggested proteolytic release of the NTR module
      in transfected cells as well as in some mouse tissues. Immunostaining during
      mouse organogenesis identified ADAMTSL5 in musculoskeletal tissues such as
      skeletal muscle, cartilage and bone, as well as in many epithelia. Affinity
      chromatography demonstrated heparin-binding of ADAMTSL5 through its NTR-module.
      Recombinant ADAMTSL5 bound to both fibrillin-1 and fibrillin-2, and co-localized
      with fibrillin microfibrils in the extracellular matrix of cultured fibroblasts,
      but without discernible effect on microfibril assembly. ADAMTSL5 is the first
      family member shown to bind both fibrillin-1 and fibrillin-2. Like other ADAMTS
      proteins implicated in microfibril biology through identification of human and
      animal mutations, ADAMTSL5 could have a role in modulating microfibril functions.

PMID- 23010573
TI  - DUXO, a novel double homeobox transcription factor, is a regulator of the
      gastrula organizer in human embryonic stem cells.
AB  - Human embryonic stem cells differentiate into gastrula organizer cells that
      express typical markers and induce secondary axes when injected into frog
      embryos. Here, we report that these human organizer cells express DUXO (DUX of
      the Organizer), a novel member of the double-homeobox (DUX) family of
      transcription factors, a group of genes unique to placental mammals. Both of
      DUXO's homeodomains share high similarity with those of Siamois and Twin, the
      initial inducers of the amphibian gastrula organizer. DUXO overexpression in
      human embryoid bodies induces organizer related genes, whereas its knock down
      hampers formation of the organizer and its derivatives. Finally, we show that
      DUXO regulates GOOSECOID, the canonical organizer marker, in a direct manner,
      suggesting that DUXO is a major regulator of human organizer formation.

PMID- 23010574
TI  - Potentiation of anti-angiogenic activity of heparin by blocking the ATIII
      interacting pentasaccharide unit and increasing net anionic charge.
AB  - Heparin, a potent anticoagulant used for the prevention of venous
      thromboembolism, has been recognized as a tumor angiogenesis inhibitor. Its
      limitation in clinical application for cancer therapy, however, arises from its
      strong anticoagulant activity, which causes associated adverse effects. In this
      study, we show the structural correlation of LHT7, a previously developed heparin
      based angiogenesis inhibitor, with its influence on VEGF blockade and its
      decreased anticoagulant activity. LHT7 was characterized as having average seven
      molecules of sodium taurocholates conjugated to one molecule of low-molecular
      weight heparin (LMWH). This study showed that the conjugation of sodium
      taurocholates selectively blocked interaction with antithrombin III (ATIII) while
      enhancing the binding with VEGF. This resulted in LHT7 to have negligible
      anticoagulant activity but potent anti-angiogenic activity. Following up on this
      finding, we showed that the bidirectional effect of sodium taurocholate
      conjugation was due to its unique structure, that is, the sterane core hindering
      the ATIII-binding pentasaccharide unit of LMWH with its bulky and rigid
      structural characteristics while the terminal sulfate group interacts with VEGF
      to produce stronger binding. In addition, we showed that LHT7 was localized in
      the tumor, especially on the endothelial cells. One explanation for this might be
      that LHT7 was delivered to the tumor via platelets.

PMID- 23010575
TI  - Directing tissue morphogenesis via self-assembly of vascular mesenchymal cells.
AB  - Rebuilding injured tissue for regenerative medicine requires technologies to
      reproduce tissue/biomaterials mimicking the natural morphology. To reconstitute
      the tissue pattern, current approaches include using scaffolds with specific
      structure to plate cells, guiding cell spreading, or directly moving cells to
      desired locations. However, the structural complexity is limited. Also, the
      artificially-defined patterns are usually disorganized by cellular self
      organization in the subsequent tissue development, such as cell migration and
      cell-cell communication. Here, by working in concert with cellular self
      organization rather than against it, we experimentally and mathematically
      demonstrate a method which directs self-organizing vascular mesenchymal cells
      (VMCs) to assemble into desired multicellular patterns. Incorporating the
      inherent chirality of VMCs revealed by interfacing with microengineered
      substrates and VMCs' spontaneous aggregation, differences in distribution of
      initial cell plating can be amplified into the formation of striking radial
      structures or concentric rings, mimicking the cross-sectional structure of liver
      lobules or osteons, respectively. Furthermore, when co-cultured with VMCs, non
      pattern-forming endothelial cells (ECs) tracked along the VMCs and formed a
      coherent radial or ring pattern in a coordinated manner, indicating that this
      method is applicable to heterotypical cell organization.

PMID- 23010576
TI  - Cruoricaptor ignavus gen. nov., sp. nov., a novel bacterium of the family
      Flavobacteriaceae isolated from blood culture of a man with bacteraemia.
AB  - A Gram-reaction-negative bacterium, strain IMMIB L-12475(T), was isolated from
      blood cultures of a human with septicaemia. The yellowish orange pigmented strain
      contained flexirubin pigment. Phylogenetic analysis based on 16S rRNA gene
      sequence revealed that strain IMMIB L-12475(T) belonged to the family
      Flavobacteriaceae, forming a distinct phyletic line that is distantly related
      (79.1-89.4% sequence similarity) to described genera of this family. Membership
      to the family was confirmed by a fatty acid profile consisting of branched-chain
      and 3-hydroxy fatty acids with major amounts of iso-C(17:0) 3-OH and iso-C(15:0),
      by the presence of menaquinone MK-6 as the only respiratory quinone and a
      polyamine pattern that contained sym-homospermidine as major component. The
      phospholipids consisted of phosphatidylethanolamine and an unknown phospholipid.
      The genomic DNA mol% G+C content was 45.6%. The distant phylogenetic position as
      compared to other representative of the family and the significant phenotypic
      properties such as pigment composition, morphology, and physiology support the
      proposal of a novel genus and species Cruoricaptor ignavus gen. nov., sp. nov.
      The type strain is IMMIB L-12475(T) (=DSM 25479(T)=CCUG 62025(T)).

PMID- 23010577
TI  - A novel mutation in the transmembrane nonpore region of the KCNH2 gene causes
      severe clinical manifestations of long QT syndrome.
AB  - BACKGROUND: Long QT syndrome (LQTS) is characterized by prolonged ventricular
      repolarization and variable clinical course with arrhythmia-related syncope and
      sudden death. Mutations in the nonpore region of the LQTS-associated KCNH2 gene
      (also known as hERG) are mostly associated with coassembly or trafficking
      abnormalities, resulting in haplotype insufficiency and milder clinical
      phenotypes compared with mutations in the pore domain. OBJECTIVE: To investigate
      the effect of a nonpore mutation on the channel current, which was identified
      from an LQTS family with severe clinical phenotypes. METHODS: Two members of a
      Japanese family with LQTS were searched for mutations in KCNQ1, KCNH2, SCN5A,
      KCNE1, KCNE2, and KCNJ2 genes by using automated DNA sequencing. We characterized
      the electrophysiological properties and glycosylation pattern of the mutant
      channels by using patch clamp recording and Western blot analysis. RESULTS: In
      the LQTS patient with torsades de pointes and cardiopulmonary arrest, we
      identified the novel T473P mutation in the transmembrane nonpore region of KCNH2.
      The proband's father carried the same mutation and showed prolonged corrected QT
      interval and frequent torsades de pointes in the presence of hypokalemia
      following the administration of garenoxacin. Patch clamp analysis in heterologous
      cells showed that hERG T473P channels generated no current and exhibited a
      dominant negative effect when coexpressed with wild-type protein. Only
      incompletely glycosylated hERG T473P channels were observed by using Western blot
      analysis, suggesting impaired trafficking. CONCLUSIONS: These results
      demonstrated that a trafficking-deficient mutation in the transmembrane nonpore
      region of KCNH2 causes a dominant negative effect and a severe clinical course in
      affected patients.

PMID- 23010578
TI  - The neural substrates of inferential and referential semantic processing.
AB  - INTRODUCTION: A distinction has been proposed, on theoretical grounds, between
      referential and inferential semantic abilities. The former account for the
      relationship of words to the world, the latter for the relationship of words
      among themselves. The hypothesis of, at least partially, different neurological
      underpinnings for this distinction has been supported by the presence of double
      dissociations in neurological patients between tasks that can be considered to
      tap the cognitive processes involving these two different classes of semantic
      knowledge, such as, for example, picture naming (referential) and naming to a
      verbal definition (inferential). METHODS: We report here the results of a
      functional magnetic resonance experiment, contrasting the pattern of brain
      activity associated with, respectively, "referential" (picture naming, word-to
      picture matching) and "inferential" (naming to definition, word-to-word matching)
      tasks. RESULTS: All tasks activate an extensive set of brain areas involving both
      hemispheres, corresponding to the "common semantic network". In addition, left
      hemispheric temporal areas are selectively engaged by the inferential tasks.
      Conversely, a specific activation of the right fusiform gyrus is associated with
      the referential tasks. CONCLUSIONS: These findings suggest that while inferential
      tasks, as compared with referential tasks, engage additional processing resources
      subserved by left hemispheric language areas involved in lexical retrieval,
      referential tasks (as compared with inferential tasks) recruit right hemispheric
      areas generally associated with nonverbal conceptual and structural object
      processing. These findings are compatible with the double dissociations reported
      in neurological patients.

PMID- 23010579
TI  - Recombinant human hepatocyte growth factor transfection alleviates hyperkinetic
      pulmonary artery hypertension in rabbit models.
AB  - OBJECTIVE: The study objective was to investigate the effect of recombinant human
      hepatocyte growth factor gene transfection via an endotracheal approach on
      hyperkinetic pulmonary artery hypertension rabbit models. METHODS: The rabbits
      with established pulmonary artery hypertension were separated into a gene
      transfection group (rabbits treated with intratracheal instillation of human
      hepatocyte growth factor 2 * 10(9) plaque-forming units coded by replication
      defective recombinant adenovirus), an empty vector group, and a control group.
      Two weeks after endotracheal gene transfection, immunohistochemistry examination
      and Western blot were used to detect the protein expression of human hepatocyte
      growth factor. The hemodynamic data were measured, and pulmonary angiography was
      performed to investigate the pulmonary collateral vessels. The vascular density
      in lung also was analyzed. RESULTS: Two weeks after gene transfection, human
      hepatocyte growth factor was expressed in the gene transfection group. The mean
      pulmonary artery pressure in the gene transfection group was lower than in the
      control and empty vector groups (P < .05 for both). The arteriolar density in the
      lung tissues of the gene transfection group was higher than in the other groups
      (P < .05), which was confirmed by immunohistochemistry, double-labeling
      immunofluorescence, and pulmonary angiography. CONCLUSIONS: Human hepatocyte
      growth factor was expressed in rabbit lung after gene transfection via an airway
      approach. Recombinant human hepatocyte growth factor transfection ameliorates the
      pulmonary artery hypertension induced by shunt flow by promoting angiogenesis in
      lung tissues.

PMID- 23010580
TI  - Tricuspid regurgitation and right ventricular function after mitral valve surgery
      with or without concomitant tricuspid valve procedure.
AB  - OBJECTIVES: To study the effect of mitral valve repair with or without
      concomitant tricuspid valve repair on functional tricuspid regurgitation and
      right ventricular function. METHODS: From 2001 to 2007, 1833 patients with
      degenerative mitral valve disease, a structurally normal tricuspid valve, and no
      coronary artery disease underwent mitral valve repair, and 67 underwent
      concomitant tricuspid valve repair. Right ventricular function (myocardial
      performance index and tricuspid annular plane systolic excursion) was measured
      before and after surgery using transthoracic echocardiography for randomly
      selected patients with tricuspid regurgitation grade 0, 1+, and 2+ (100 patients
      for each grade) and 93 with grade 3+/4+, 393 patients in total. RESULTS: In
      patients with mild (<3+) preoperative tricuspid regurgitation, mitral valve
      repair alone was associated with reduced tricuspid regurgitation and mild
      worsening of right ventricular function. Tricuspid regurgitation of 2+ or greater
      developed in fewer than 20%, and right ventricular function had improved, but not
      to preoperative levels, at 3 years. In patients with severe (3+/4+) preoperative
      tricuspid regurgitation, mitral valve repair alone reduced tricuspid
      regurgitation and improved right ventricular function; however, tricuspid
      regurgitation of 2+ or greater returned and right ventricular function worsened
      toward preoperative levels within 3 years. Concomitant tricuspid valve repair
      effectively eliminated severe tricuspid regurgitation and improved right
      ventricular function. Also, over time, tricuspid regurgitation did not return and
      right ventricular function continued to improve to levels comparable to that of
      patients with lower grades of preoperative tricuspid regurgitation. CONCLUSIONS:
      In patients with mitral valve disease and severe tricuspid regurgitation, mitral
      valve repair alone was associated with improved tricuspid regurgitation and right
      ventricular function. However, the improvements were incomplete and temporary. In
      contrast, concomitant tricuspid valve repair effectively and durably eliminated
      severe tricuspid regurgitation and improved right ventricular function toward
      normal, supporting an aggressive approach to important functional tricuspid
      regurgitation.

PMID- 23010581
TI  - Durability of pericardial versus porcine bioprosthetic heart valves.
AB  - OBJECTIVES: To compare the probability, and modes, of explantation for Carpentier
      Edwards pericardial versus porcine valves. METHODS: Our porcine series began in
      1974 and our pericardial series in 1991, with annual prospective follow-up. We
      used the Kaplan-Meier method and Cox regression for estimation and analysis of
      patient mortality, and the cumulative incidence function and competing risks
      regression for estimation and analysis of valve durability. RESULTS: Through the
      end of 2010, we had implanted 506 porcine and 2449 pericardial aortic valves and
      181 porcine and 163 pericardial mitral valves. The corresponding total and
      maximum follow-up years were 3471 and 24, 11,517 and 18, 864 and 22, and 645 and
      9. The corresponding probabilities (cumulative incidence function) of any valve
      explant were 7%, 8%, 22%, and 8%, and of explant for structural valve
      deterioration were 4%, 5%, 16%, and 5% at 15 years for the first 3 series and at
      8 years for the fourth (pericardial mitral valve) series. Using competing risks
      regression for structural valve deterioration explant, with age, gender, valve
      size, and concomitant coronary bypass surgery as covariates, a slight (subhazard
      ratio, 0.79), but nonsignificant, protective effect was found for the pericardial
      valve in the aortic position and a greater (subhazard ratio, 0.31) and almost
      significant (P = .08) protective effect of the pericardial valve in the mitral
      position. Leaflet tear was responsible for 61% of the structural valve
      deterioration explants in the porcine series and 46% in the pericardial series.
      CONCLUSIONS: Using competing risks regression, the pericardial valve had a
      subhazard ratio for structural valve deterioration explant of less than 1 in both
      positions, approaching statistical significance in the mitral position. The mode
      of structural valve deterioration was predominantly leaflet tear for porcine
      valves and fibrosis/calcification for pericardial valves.

PMID- 23010582
TI  - Imaging of vascular remodeling after simulated thoracoabdominal aneurysm repair.
AB  - OBJECTIVE: A better understanding of the response of the spinal cord blood supply
      to segmental artery (SA) sacrifice should help minimize the risk of paraplegia
      after both open and endovascular repair of thoracoabdominal aortic (TAA)
      aneurysms. METHODS: Twelve female juvenile Yorkshire pigs were randomized into 3
      groups and perfused with a barium-latex solution. Pigs in group 1 (control) had
      infusion without previous intervention. Pigs in group 2 were infused 48 hours
      after ligation of all SAs (T4-L5) and those in group 3 at 120 hours after
      ligation. Postmortem computed tomographic scanning of the entire pig enabled
      overall comparisons and measurement of vessel diameters in the spinal cord
      circulation. RESULTS: We ligated 14.5 +/- 0.8 SAs: all filled retrograde to the
      ligature. Paraplegia occurred in 38% of operated pigs. A significant increase in
      the mean diameter of the anterior spinal artery (ASA) was evident after SA
      sacrifice (P < .0001 for 48 hours and 120 hours). The internal thoracic and
      intercostal arteries also increased in diameter. Quantitative assessment showed
      an increase in vessel density 48 hours after ligation of SAs, reflected by an
      obvious increase in small collateral vessels seen on 3-dimensional
      reconstructions of computed tomographic scans at 120 hours. CONCLUSIONS:
      Remodeling of the spinal cord blood supply--including dilatation of the ASA and
      proliferation of small collateral vessels--is evident at 48 and 120 hours after
      extensive SA sacrifice. It is likely that exploitation of this process will prove
      valuable in the quest to eliminate paraplegia after TAA aneurysm repair.

PMID- 23010584
TI  - [Not Available].

PMID- 23010583
TI  - Distinctive roles of PLD signaling elicited by oxidative stress in synaptic
      endings from adult and aged rats.
AB  - The role of iron in oxidative injury in the nervous system has been extensively
      described. However, little is known about the role of lipid signal transduction
      in neurodegeneration processes triggered by iron overload. The purpose of this
      work was to characterize the regulation and the crosstalk between
      phosphatidylcholine (PC)-derived diacylglycerol (DAG) and cannonical signaling
      pathways during iron-induced oxidative stress in cerebral cortex synaptic endings
      (Syn) obtained from adult (4 months old) and aged (28 months old) rats. DAG
      production was increased in Syn exposed to iron. This rise in DAG formation was
      due to phospholipase D1 (PLD1) and PLD2 activations. In adult rats, PKD1, ERK1/2
      and PKCalpha/betaII activations were PLD1 and PLD2 dependent. In contrast, in
      senile rats, DAG formation catalyzed by PLDs did not participate in PKD1, ERK1/2
      and PKCalpha/betaII regulations, but it was dependent on ERK and PKC activities.
      Iron-induced oxidative stress promoted an increased localization of PLD1 in
      membrane rafts, whereas PLD2 was excluded from these domains and appeared to be
      involved in glutamate transporter function. Our results show a differential
      regulation and synaptic function of DAG generated by PLDs during iron-induced
      oxidative stress as a consequence of aging.

PMID- 23010586
TI  - Texture feature ranking with relevance learning to classify interstitial lung
      disease patterns.
AB  - OBJECTIVE: The generalized matrix learning vector quantization (GMLVQ) is used to
      estimate the relevance of texture features in their ability to classify
      interstitial lung disease patterns in high-resolution computed tomography images.
      METHODOLOGY: After a stochastic gradient descent, the GMLVQ algorithm provides a
      discriminative distance measure of relevance factors, which can account for
      pairwise correlations between different texture features and their importance for
      the classification of healthy and diseased patterns. 65 texture features were
      extracted from gray-level co-occurrence matrices (GLCMs). These features were
      ranked and selected according to their relevance obtained by GMLVQ and, for
      comparison, to a mutual information (MI) criteria. The classification performance
      for different feature subsets was calculated for a k-nearest-neighbor (kNN) and a
      random forests classifier (RanForest), and support vector machines with a linear
      and a radial basis function kernel (SVMlin and SVMrbf). RESULTS: For all
      classifiers, feature sets selected by the relevance ranking assessed by GMLVQ had
      a significantly better classification performance (p<0.05) for many texture
      feature sets compared to the MI approach. For kNN, RanForest, and SVMrbf, some of
      these feature subsets had a significantly better classification performance when
      compared to the set consisting of all features (p<0.05). CONCLUSION: While this
      approach estimates the relevance of single features, future considerations of
      GMLVQ should include the pairwise correlation for the feature ranking, e.g. to
      reduce the redundancy of two equally relevant features.

PMID- 23010587
TI  - Black sentinel lymph node and 'scary stickers'.
AB  - An unusual case is presented of a young adult patient with two black-stained,
      radio-nucleotide tracer-active sentinel lymph nodes biopsied following her
      primary cutaneous melanoma treatment. This was subsequently confirmed to be
      secondary to cutaneous tattoos, averting the need of an elective regional node
      dissection. History of tattooing and tattoo removal should therefore be obtained
      as a routine in all melanoma patients considered for sentinel node biopsy (SLN).
      SLN biopsy and any subsequent completion node dissection should be strictly
      staged so that proper histologic diagnosis of the sentinel node is available for
      correct decision making and treatment.

PMID- 23010588
TI  - The use of a silicone flexor tendon as a teaching model for flexor tendon repair:
      a clear view.

PMID- 23010589
TI  - LeFort I osteotomy and secondary procedures in full-face transplant patients.
AB  - Composite tissue allotransplantion has been the latest addition to reconstructive
      plastic surgery of limbs and faces. These techniques have opened up a new
      paradigm in reconstruction. However, plastic surgeons will have to face a new
      patient population that receives the application of vascularised tissue
      allografts and immunosuppression. Secondary surgery may be necessary in this
      population, especially in the transplanted tissues, to improve aesthetics and
      function following the transplant, although little is known regarding the exact
      clinical protocol to be followed and the feasibility of standard plastic surgery
      techniques on transplanted tissues. We present our experience of a LeFort I
      osteotomy, limited ritidectomy and blepharoplasty in a full-face transplant
      recipient.

PMID- 23010590
TI  - Structural insight into the interaction of ADP-ribose with the PARP WWE domains.
AB  - The WWE domain is often identified in proteins associated with ubiquitination or
      poly-ADP-ribosylation. Structural information about WWE domains has been obtained
      for the ubiquitination-related proteins, such as Deltex and RNF146, but not yet
      for the poly-ADP-ribose polymerases (PARPs). Here we determined the solution
      structures of the WWE domains from PARP11 and PARP14, and compared them with that
      of the RNF146 WWE domain. NMR perturbation experiments revealed the specific
      differences in their ADP-ribose recognition modes that correlated with their
      individual biological activities. The present structural information sheds light
      on the ADP-ribose recognition modes by the PARP WWE domains.

PMID- 23010591
TI  - Structural features of human histone acetyltransferase p300 and its complex with
      p53.
AB  - The protein p300 is a multifunctional transcriptional coactivator that plays
      pivotal role in several cellular functions. Although structures of several
      domains have been solved in isolation, the structures of full-length protein
      (p300 FL) or its complexes with transcription activators are completely unknown.
      Herein, we applied atomic force microscopy to visualize p300 FL. We found that it
      is almost prolate ellipsoidal in shape, having several bulges. We further
      identified the functionally significant N-terminal and C-terminal regions, by
      applying domain-specific antibodies and found that they are located near one end
      and centre of the molecule, respectively. Importantly, we have visualized the
      complex between p300 FL and tumor suppressor protein p53. The relevance of these
      data in understanding dynamics of p300 during acetylation and transcription will
      be mentioned.

PMID- 23010592
TI  - NOK/STYK1 interacts with GSK-3beta and mediates Ser9 phosphorylation through
      activated Akt.
AB  - NOK (also known as STYK1) has been identified as an oncogene. However, its
      biochemical and biological activities as a molecular regulator are poorly
      defined. In the present study, we report that NOK overexpression led to enhanced
      phosphorylation of GSK-3beta at its Ser9 residue via Akt phosphorylation at
      Thr308. NOK could make complexes with both Akt and GSK-3beta. Moreover, the
      expression levels of NOK, p-Akt(Thr308) and p-GSK-3beta(Ser9) were positively
      correlated in cancerous and non-cancerous breast cell lines. Thus, our data
      identified a novel functional molecular complex formed by NOK, Akt and GSK-3beta
      that may relay a NOK-directed tumourigenic cascade.

PMID- 23010593
TI  - Functional characterization of a novel Mn2+ dependent protein serine/threonine
      kinase KpnK, produced by Klebsiella pneumoniae strain MGH78578.
AB  - Klebsiella pneumoniae MGH78578 contains ~500 uncharacterized signaling proteins
      and in this study, we characterized the biological functions of a novel
      eukaryotic-like serine/threonine kinase; ESTK (KpnK). Studies demonstrated that
      KpnK undergoes autophosphorylation within the pH range 7.0-7.5 at 37 degrees C in
      a time- and concentration- dependent manner, with Mn(2+) as its cofactor. The
      DeltakpnK mutant exhibited higher sensitivity to gastrointestinal and oxidative
      stresses. Deletion of kpnK resulted in a two to threefold increased
      susceptibility towards imipenem, cefepime, ceftriaxone and ceftazidime. Our study
      has provided overall evidence for the involvement of ESTK in regulating bacterial
      physiology, stress response and drug resistance. This report has unmasked the
      occurrence of Ser/Thr kinase mediated signaling for the first time in K.
      pneumoniae.

PMID- 23010595
TI  - Elevated level of human RPA interacting protein alpha (hRIPalpha) in cervical
      tumor cells is involved in cell proliferation through regulating RPA transport.
AB  - Replication protein A (RPA) is a eukaryotic single-stranded DNA binding protein
      that is essential for DNA replication, repair, and recombination, and human RPA
      interacting protein alpha (hRIPalpha) is the nuclear transporter of RPA. Here, we
      report the regulatory role of hRIPalpha protein in cell proliferation. Western
      blot analysis revealed that the level of hRIPalpha was frequently elevated in
      cervical tumors tissues and hRIPalpha knockdown by siRNA inhibited cellular
      proliferation through deregulation of the cell cycle. In addition, overexpression
      of hRIPalpha resulted in increased clonogenicity. These results indicate that
      hRIPalpha is involved in cell proliferation through regulation of RPA transport.

PMID- 23010594
TI  - Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core
      protein.
AB  - Aminoacylase 3 (AA3) mediates deacetylation of N-acetyl aromatic amino acids and
      mercapturic acids. Deacetylation of mercapturic acids of exo- and endobiotics are
      likely involved in their toxicity. AA3 is predominantly expressed in kidney, and
      to a lesser extent in liver, brain, and blood. AA3 has been recently reported to
      interact with the hepatitis C virus core protein (HCVCP) in the yeast two-hybrid
      system. Here we demonstrate that AA3 directly binds to HCVCP (K(d) ~10 MUM) that
      may by implicated in HCV pathogenesis. AA3 also revealed a weak endopeptidase
      activity towards the N-terminus of HCVCP.

PMID- 23010596
TI  - Site-specific cleavage of mutant ABL mRNA by DNAzyme is facilitated by peptide
      nucleic acid binding to RNA substrate.
AB  - RNA-cleaving DNAzymes were constructed to target the point mutation in the BCR
      ABL transcript that causes imatinib resistance in leukemic cells. We examined the
      effect of 12mer peptide nucleic acids (PNAs) as facilitator oligonucleotides that
      bind to RNA substrate at the termini of the DNAzyme to improve DNAzyme-mediated
      cleavage of full-length RNA. When imatinib-resistant cells were transfected with
      the facilitator PNA and DNAzyme, DNAzyme activity was enhanced and the cells were
      sensitized to imatinib treatment. Thus, facilitator PNA may be used to enhance
      activity of antisense oligonucleotide targeting the full-length transcript.

PMID- 23010597
TI  - miR-134 inhibits epithelial to mesenchymal transition by targeting FOXM1 in non
      small cell lung cancer cells.
AB  - Recent studies have implied that miRNAs act as crucial modulators for epithelial
      to-mesenchymal transition (EMT). We found that miR-134 expression correlated with
      invasive potential and EMT phenotype of NSCLC cells. Functional assays
      demonstrated that miR-134 inhibited EMT in NSCLC cells. In addition, we showed
      that Forkhead Box M1 (FOXM1) is a direct target of miR-134. Knockdown of FOXM1
      reversed EMT resembling that of miR-134 overexpression. We further found that
      FOXM1 was involved in TGF-beta1-induced EMT in A549 cells. These findings suggest
      that miR-134 acts as a novel EMT suppressor in NSCLC cells.

PMID- 23010598
TI  - Homodimeric pregnancy-associated plasma protein-A in normal human placenta of
      first and third trimester of pregnancy: biochemical and morphological
      observations.
AB  - Insulin-like growth factors (IGFs) become bio-available following hydrolysis of
      binding proteins by homodimeric PAPP-A (dPAPP-A); this is a metzincin associated
      with the membranes of trophoblast phenotypes, the precise placental localization
      of which was unknown. Our study on placental samples of the first trimester shows
      the immunohistochemical localization of proMBP and dPAPP-A in the same cells. In
      contrast, dPAPP-A is mainly negative in the syncytium (ST) and positive in the
      villous cytotrophoblast (VCT) while htPAPP-A is strongly expressed in the ST and
      negative in the VCT at term, suggesting a progressive deactivation of the enzyme
      with gestational age. In agreement with the above, dPAPP-A is released only by
      first trimester placental explants in culture.

PMID- 23010599
TI  - The influence of the Tubingen soft palate plate and early cleft closure on the
      nasopharyngeal airway for the management of airway obstruction in an infant with
      Pierre Robin sequence: A case report.
AB  - INTRODUCTION: A Tubingen palate plate and early cleft closure for successful
      airway management is described in a newborn with Pierre Robin sequence.
      PRESENTATION OF CASE: A three-day-old newborn with an acute airway obstruction
      underwent primary treatment with a Tubingen soft palate plate. DISCUSSION: After
      stabilization of the airway, the cleft soft palate was closed after three months.
      CONCLUSION: The Tubingen soft palate plate proved to be a very satisfactory
      treatment for the infant.

PMID- 23010600
TI  - Determination of esculentoside A in dog plasma by LC-MS/MS method: application to
      pre-clinical pharmacokinetics.
AB  - A simple and rapid high performance liquid chromatography electrospray ionization
      ion-trap tandem mass spectrometry (LC-MS/MS) method has been developed and
      validated for the quantitative determination of esculentoside A (EsA) in dog
      plasma using ginsenoside Rg1 as the internal standard (IS). After liquid-liquid
      extraction (LLE) with n-butanol, the analyte and IS were separated on a Diamonsil
      C(18) (2.1 mm * 50 mm, 3 MUm) column with the mobile phase of methanol-water
      containing 0.1% acetic acid (70:30, v/v) at a flow rate of 0.2 ml/min. An ion
      trap mass spectrometer equipped with an electrospray ionization source performed
      in selected reaction monitoring (SRM) mode was used as the detector. The
      precursor-product ion transitions were m/z 849.3 [M+Na](+)->m/z 805.3 for EsA and
      m/z 823.3 [M+Na](+)->m/z 643.3 for IS. The total chromatographic run time was 5
      min. The method was sensitive enough with a lower limit of quantitation (LLOQ) of
      5 ng/ml and had a good linearity (r(2)>0.997) over the linear range of 5-500
      ng/ml. The mean extraction recovery of EsA from spiked plasma samples was over
      75%. The intra- and inter-precisions were no more than 8.8% and accuracies were
      within the range of -4.6 to 8.7%. All the validated data were within the accepted
      criteria as stated in the FDA bioanalytical method validation guideline. The
      developed method was suitable for the quantification of EsA and successfully
      applied to the pharmacokinetic study of EsA after an oral administration to
      beagle dogs.

PMID- 23010601
TI  - Safety and pharmacokinetics of a human monoclonal antibody to rabies virus: a
      randomized, dose-escalation phase 1 study in adults.
AB  - BACKGROUND: Rabies is an essentially fatal disease that is preventable with the
      timely administration of post-exposure prophylaxis (PEP). The high cost of PEP,
      which includes vaccine and hyperimmune globulin, is an impediment to the goal of
      preventing rabies in the developing world. Recently a recombinant human IgG(1)
      anti-rabies monoclonal antibody (SII RMab) has been developed in India to replace
      serum-derived rabies immunoglobulin. The present study was conducted to
      demonstrate the safety of SII RMab and to determine the dose resulting in
      neutralizing serum antibody titers comparable to human rabies immunoglobulin
      (HRIG) when administered in conjunction with rabies vaccine in a simulated PEP
      regimen. METHODS: This randomized, open label, dose-escalation phase 1 study was
      conducted in healthy adults at a large tertiary care, referral, public hospital
      in India. Safety was assessed by active surveillance for adverse events along
      with standard laboratory evaluations and measurement of anti-drug antibodies
      (ADA). Anti-rabies antibody levels were measured by rapid fluorescent focus
      inhibition test (RFFIT) and ELISA. The study duration was 365 days. FINDINGS: SII
      RMab was well tolerated with similar frequency of local injection site reactions
      to HRIG. The geometric mean concentrations of rabies neutralizing antibody in the
      vaccine plus SII RMab 10 IU/kg cohort were comparable to the vaccine plus HRIG 20
      IU/kg cohort throughout the 365-day study period; day 14 geometric mean
      concentrations 23.4 IU/ml (95% CI 14.3, 38.2) vs. 15.3 IU/ml (95% CI 7.72, 30.3;
      p=NS), respectively. Future post-exposure prophylaxis studies of SII RMab at a
      dose of 10 IU/kg in conjunction with vaccine are planned.

PMID- 23010603
TI  - Treatment intensification for head and neck carcinoma: do we have a verdict?

PMID- 23010602
TI  - DSG3 as a biomarker for the ultrasensitive detection of occult lymph node
      metastasis in oral cancer using nanostructured immunoarrays.
AB  - OBJECTIVES: The diagnosis of cervical lymph node metastasis in head and neck
      squamous cell carcinoma (HNSCC) patients constitutes an essential requirement for
      clinical staging and treatment selection. However, clinical assessment by
      physical examination and different imaging modalities, as well as by histological
      examination of routine lymph node cryosections can miss micrometastases, while
      false positives may lead to unnecessary elective lymph node neck resections.
      Here, we explored the feasibility of developing a sensitive assay system for
      desmoglein 3 (DSG3) as a predictive biomarker for lymph node metastasis in HNSCC.
      MATERIALS AND METHODS: DSG3 expression was determined in multiple general cancer-
      and HNSCC-tissue microarrays (TMAs), in negative and positive HNSCC metastatic
      cervical lymph nodes, and in a variety of HNSCC and control cell lines. A
      nanostructured immunoarray system was developed for the ultrasensitive detection
      of DSG3 in lymph node tissue lysates. RESULTS: We demonstrate that DSG3 is highly
      expressed in all HNSCC lesions and their metastatic cervical lymph nodes, but
      absent in non-invaded lymph nodes. We show that DSG3 can be rapidly detected with
      high sensitivity using a simple microfluidic immunoarray platform, even in human
      tissue sections including very few HNSCC invading cells, hence distinguishing
      between positive and negative lymph nodes. CONCLUSION: We provide a proof of
      principle supporting that ultrasensitive nanostructured assay systems for DSG3
      can be exploited to detect micrometastatic HNSCC lesions in lymph nodes, which
      can improve the diagnosis and guide in the selection of appropriate therapeutic
      intervention modalities for HNSCC patients.

PMID- 23010604
TI  - Glaucoma risk assessment using a non-linear multivariable regression method.
AB  - The present research investigates the relationship between the central corneal
      thickness (CCT), Heidelberg Retina Tomograph II (HRTII) structural measurements
      and intraocular pressure (IOP) using an innovative non-linear multivariable
      regression method in order to define the risk factors in future glaucoma
      development and patient management. The method is implemented to data from ninety
      three open angle glaucoma eyes. The results show that in established glaucoma,
      CCT is significantly associated with HRTII structural measurements (maximum
      contour depression, cup volume inferotemporally) and IOP. They are also compared
      to those obtained from the application of standard linear regression methods,
      improving the coefficient determination R(2) by 35%, exhibiting thus the
      performance of the proposed methodology.

PMID- 23010605
TI  - The impact of altered task mechanics on timing and duration of eccentric bi
      articular muscle contractions during cycling.
AB  - In order to understand muscle adaptations to altered task mechanics during
      cycling, this study investigated the impact of altered seat height and cadence on
      timing and duration of gastrocnemius (GAST), biceps femoris (BF) and vastus
      lateralis (VL) eccentric contractions and muscle activation patterns, and cycling
      economy. Ten male cyclists completed 9 * 5 min of cycling at 3 seat heights and 3
      cadences. Three-dimensional leg kinematics and muscle activation patterns were
      recorded to estimate timing of eccentric muscle contractions. Onset, offset and
      duration of eccentric contractions and, onset, offset and duration of muscle
      activation were calculated, along with cycling economy. Duration of GAST and VL
      eccentric contractions decreased with increasing seat height due to earlier
      offset of eccentric muscle contractions. Duration of BF eccentric contractions
      significantly increased with seat height due to a later eccentric contraction
      offset. Offset of GAST and BF muscle activation occurred earlier with increasing
      cadence. Cycling economy was significantly affected by cadence but not seat
      height. The results suggest that as a consequence of altered seat height,
      proprioceptive feedback is used to fine-tune the timing of bi-articular eccentric
      muscle contractions. These results may have implications for seat height self
      selection.

PMID- 23010606
TI  - Systematic identification of Lactobacillus plantarum auxotrophs for fermented
      Nham using genome-scale metabolic model.
AB  - In this study, a systematic strategy is presented, which identifies auxotrophic
      starters for the popular Thai fermented sausage product, called Nham, using a
      genome-scale metabolic model. A published genome-scale model of Lactobacillus
      plantarum WCFS1 is adopted for studying the L. plantarum BCC9546 characteristics
      cultured on Simulated Nham Broth. Single gene deletion analysis is performed to
      determine the genes essential for cell growth. Strains lacking such essential
      genes are considered potential auxotrophic mutants. Then, metabolite supplement
      analysis is introduced to determine a list of metabolites supplements for each
      mutant required to restore its growth. Herein, 9 potential auxotrophs are
      proposed for use in Nham fermentation, along with their metabolite supplements.
      Simulation studies showed that the secreted fluxes of organic acids, as well as
      amino-derived flavor compounds of these auxotrophs, are similar to those of the
      wild-type, indicating that Nham fermented by these auxotrophs would have similar
      tastes and flavors as Nham fermented by the wild-type. These proposed auxotrophs
      and corresponding nutritional supplements will be useful for the design of
      auxotroph starter culture utilized for Nham production in the laboratory. The
      systematic strategy presented here will facilitate the analysis and development
      of auxotroph starters used in the food industry.

PMID- 23010607
TI  - Attenuation of oxidative damage and inflammatory responses by apigenin given to
      mice after irradiation.
AB  - We determined the in vivo efficacy of apigenin, as an anti-oxidant and anti
      inflammatory agent, given to mice after irradiation. Various concentrations of
      apigenin (0, 10, 20, and 40mg/kg body weight) were administered to mice by a
      single intraperitoneal injection 3hr after receiving 0 or 3Gy of (137)Cs gamma
      rays. Mice receiving vehicle only (no radiation and no apigenin) served as sham
      controls. We assessed the anti-oxidative activity of apigenin in vivo by
      measuring levels of 8-hydroxy-2-deoxy guanosine (8-OH-dG) in bone marrow (BM)
      cells, collected at days 3 and 10 after irradiation, from groups of mice (5 mice
      per treatment group) with or without apigenin treatment. Simultaneously, we
      evaluated the ability of apigenin to diminish radiation-induced inflammatory
      responses in bone-marrow-derived macrophages (BMDMs) from the same individual
      mice used for measuring the level of 8-OH-dG. To do this, the levels of activated
      nuclear factor-kappa B (NF-kappa B) and NF-kappa B-regulated pro-inflammatory
      cytokines [i.e. interleukin 1-beta (IL-1beta), IL-6, and tumor necrosis factor
      alpha (TNF-alpha)] were measured in BMDMs. Our results indicated significant
      reductions (p<0.01 or <0.05) in the levels of 8-OH-dG in BM cells collected at
      both harvest times from irradiated mice receiving apigenin treatment, at all
      apigenin concentrations tested. Likewise, activation of NF-kappa B in BMDMs
      collected from gamma-irradiated mice that received apigenin was suppressed at
      both harvest times. Further, the levels of pro-inflammatory cytokines in gamma
      irradiated mice treated with 20 or 40mg/kg body weight apigenin were
      significantly lower than those in mice receiving radiation only (p<0.01 or <0.05)
      even at day 10 post-irradiation. Additionally, the ratio of neutrophils to
      lymphocytes indicated that apigenin ameliorated radiation-induced hematological
      toxicity. Our study is the first to demonstrate the mitigative/therapeutic
      effects of apigenin given to mice after irradiation.

PMID- 23010608
TI  - A multifaceted prospective memory intervention to improve medication adherence:
      design of a randomized control trial.
AB  - Adherence to prescribed antihypertensive agents is critical because control of
      elevated blood pressure is the single most important way to prevent stroke and
      other end organ damage. Unfortunately, nonadherence remains a significant
      problem. Previous interventions designed to improve adherence have demonstrated
      only small benefits of strategies that target single facets such as understanding
      medication directions. The intervention described here is informed by prospective
      memory theory and performance of older adults in laboratory-based paradigms and
      uses a comprehensive, multifaceted approach to improve adherence. It incorporates
      multiple strategies designed to support key components of prospective remembering
      involved in taking medication. The intervention is delivered by nurses in the
      home with an education control group for comparison. Differences between groups
      in overall adherence following the intervention and 6 months later will be
      tested. Systolic and diastolic blood pressure levels also will be examined
      between groups and as they relate to adherence. Intra-individual regression is
      planned to examine change in adherence over time and its predictors. Finally, we
      will examine the association between executive function/working memory and
      adherence, predicting that adherence will be related to executive/working memory
      in the control group but not in the intervention group.

PMID- 23010609
TI  - Serum high-density lipoprotein cholesterol and progression to arterial stiffness
      in middle-aged and elderly Chinese.
AB  - BACKGROUND AND AIMS: Low high-density lipoprotein cholesterol (HDL-c) is a risk
      factor for cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is
      an indicator of arterial stiffness, which is recognized as a predictor of
      cardiovascular disease. The aim of this study was to investigate the association
      between HDL-c and baPWV among middle-aged and elderly Chinese. METHODS: A total
      number of 1133 Chinese (430 men, 703 women) aged from 50 to 90 years old were
      recruited from Shanghai downtown district. The baPWV and major cardiovascular
      risk factors of the participants were measured. RESULTS: Serum HDL-c was
      negatively correlated with baPWV (r = -0.143, P < 0.001) after adjustment for age
      and gender. Multivariate linear regression analysis demonstrated that age (P <
      0.001), systolic blood pressure (P < 0.001), HDL-c (P < 0.001), smoking (P =
      0.001), BMI (P = 0.002), fasting plasma glucose (P = 0.004), and white blood cell
      (P = 0.005) were independently associated with baPWV. After multiple adjustments,
      participants in the highest quartile of HDL-c had an odds ratio of 0.442 (95% CI
      0.268-0.729) for developing high arterial stiffness compared with participants in
      the lowest quartile. The association remained significant after further
      adjustment for major cardiovascular risk factors. CONCLUSION: HDL-c has an
      independent protective effect on arterial stiffness in middle-aged and elderly
      Chinese. Early detection of HDL-c level is important in high risk populations
      with arterial stiffness. Increasing HDL-c level may be an attractive therapeutic
      target for the prevention of arterial function and subsequent disease.

PMID- 23010610
TI  - Quantification and normalization of x-ray mammograms.
AB  - The analysis of (x-ray) mammograms remains qualitative, relying on the judgement
      of clinicians. We present a novel method to compute a quantitative, normalized
      measure of tissue radiodensity traversed by the primary beam incident on each
      pixel of a mammogram, a measure we term the standard attenuation rate (SAR). SAR
      enables: the estimation of breast density which is linked to cancer risk; direct
      comparison between images; the full potential of computer aided diagnosis to be
      utilized; and a basis for digital breast tomosynthesis reconstruction. It does
      this by removing the effects of the imaging conditions under which the mammogram
      is acquired. First, the x-ray spectrum incident upon the breast is calculated,
      and from this, the energy exiting the breast is calculated. The contribution of
      scattered radiation is calculated and subtracted. The SAR measure is the scaling
      factor that must be applied to the reference material in order to match the
      primary attenuation of the breast. Specifically, this is the scaled reference
      material attenuation which when traversed by an identical beam to that traversing
      the breast, and when subsequently detected, results in the primary component of
      the pixel intensity observed in the breast image. We present results using two
      tissue equivalent phantoms, as well as a sensitivity analysis to detector
      response changes over time and possible errors in compressed thickness
      measurement.

PMID- 23010611
TI  - Paediatric pain assessment and management in the emergency setting: the impact of
      a paediatric pain bundle.
AB  - OBJECTIVES: To evaluate the impact of a paediatric pain bundle on pain assessment
      and management of children with fractured forearms who presented to an Emergency
      Department (ED). METHODS: A descriptive, comparative pilot study was conducted at
      a large regional hospital ED to describe differences in pain assessment,
      management and documentation in the 4months before and after the implementation
      of a paediatric pain bundle. RESULTS: A total of 242 children with fractured
      forearms visited the ED over two separate 4-month periods during 2009. Compared
      to the pre time period, children in the post time period did not differ
      significantly regarding pain assessment score documentation (13.5% vs. 20.7%,
      p=0.14), administration rate of analgesia (58.7% vs. 65.5%, p=0.28) or time to
      analgesia (28min vs. 35min, p=0.22). CONCLUSIONS: In this pilot study, findings
      indicated clinical significance but not statistical significance. The assessment
      and management of pain in the ED paediatric population is challenging due to
      difficulties interpreting responsiveness and to organisational and system
      imperatives that delay time critical aspects such as time to analgesia. Further
      focus on documentation, assessment and management practices is required in larger
      populations across a number of sites.

PMID- 23010612
TI  - Increased intracranial pressure is associated with the development of acute lung
      injury following severe traumatic brain injury.
AB  - OBJECTIVE: This study investigated the relationship among intracranial pressure
      (ICP), the development of acute lung injury (ALI) and systemic inflammatory
      response syndrome (SIRS) following a severe traumatic brain injury (TBI).
      METHODS: Post-traumatic ICP was continuously monitored for the first week
      following injury in a series of consecutive patients with isolated severe TBI.
      The initial ICP and the duration of intracranial hypertension (ICH) were
      calculated. The risk factors associated with the development of ALI and SIRS were
      evaluated. RESULTS: Of the 86 patients enrolled, 22 patients developed ALI and 52
      patients developed SIRS during the observation period. The patients with ALI
      presented with a significantly higher initial ICP (31.3+/-7.8 mmHg vs. 23.0+/-8.8
      mmHg, p<0.001) and a longer duration of ICH (16.8+/-6.5 h vs. 11.9+/-6.0 h,
      p=0.002) than those without ALI. The incidence of both ALI and SIRS increased
      with increasing initial ICP, and the presence of SIRS was associated with a
      fourfold increase in the risk of developing ALI (odds ratio [OR], 4.0; 95%
      confidence interval [CI], 1.2-13.0). CONCLUSIONS: Increased ICP is associated
      with increased risks of developing ALI and SIRS following severe TBI. Future
      studies designed to verify the causative relationship between increased ICP and
      the systemic responses are warranted.

PMID- 23010613
TI  - Complete segmentation failure causing non-dysjunction of os odontoideum and
      hypertrophic C1 arch: a case report.

PMID- 23010614
TI  - The impact of preoperative immunonutrition and other nutrition models on tumor
      infiltrative lymphocytes in colorectal cancer patients.
AB  - AIM: The importance of the alteration of tumor infiltrative lymphocytes (CD4(+),
      CD8(+), CD16(+), and CD56(+)) in colorectal cancer prognosis is well known. In
      this study, we analyzed the effect of preoperative immunonutrition and different
      nutritional models on the clinical condition of colorectal cancer patients.
      METHODS: Twenty-eight colorectal cancer patients were grouped into 4 groups
      according to their nutrition regimens randomly and were given immunonutrition
      (IMN), standard enteral (SE), total parental nutrition (TPN), and normal
      nutrition (NN) regimens, all of which contained the same calorie-nitrogen content
      within a 7-day preoperative period. All patients had an endoscopic biopsy before
      and after the regimen, and the lymphocyte population infiltrating mucosal parts
      of the resected tumor tissue were evaluated. Immunohistochemical analysis of the
      tissue specimens was performed by staining with antihuman CD4(+), CD8(+),
      CD16(+), and CD56(+) antibodies. RESULTS: After nutrition, there were significant
      increases in each of the 4 groups of CD4(+) and CD8(+) cells within the tumor.
      Comparing the rates of augmentation, the increased rates of the CD8(+) cells
      infiltrating the tumor after nutrition in the patients who were fed with IMN were
      significantly more than the ones in other groups (P = .01). CD16(+) cell
      infiltration was significantly higher in all groups except the SE and IMN groups.
      The SE group had increased CD56(+) cell infiltration compared with the other
      groups. CONCLUSIONS: In the colorectal cancer patients who had nutrition in the 7
      day preoperative period, except for the SE nutrition group, there were
      significant increases of infiltration of CD56(+) cells at the mucosal part of the
      tumor tissue within the CD4(+) and CD8(+) cell population. When postnutrition
      values were compared, there was a marked increase of CD8(+) cells in the IMN
      group.

PMID- 23010615
TI  - Characteristics and costs of surgical scheduling errors.
AB  - BACKGROUND: Errors that increase the risk of wrong-side/-site procedures not only
      occur the day of surgery but also are often introduced much earlier during the
      scheduling process. The frequency of these booking errors and their effects are
      unclear. METHODS: All surgical scheduling errors reported in the institution's
      medical event reporting system from January 1, 2011, to July 31, 2011, were
      analyzed. Focus groups with operating room nurses were held to discuss delays
      caused by scheduling errors. RESULTS: Of 17,606 surgeries, there were 151 (.86%)
      booking errors. The most common errors were wrong side (55, 36%), incomplete (38,
      25%), and wrong approach (25, 17%). Focus group participants said incomplete and
      wrong-approach bookings resulted in the longest delays, averaging 20 minutes and
      costing at least $320. CONCLUSIONS: Although infrequent, scheduling errors
      disrupt operating room team dynamics, causing delays and bearing substantial
      costs. Further research is necessary to develop tools for more accurate
      scheduling.

PMID- 23010616
TI  - Between a rock and a hard place: commentary on "adverse cardiac events in
      patients with coronary stents undergoing noncardiac surgery: a systematic
      review".

PMID- 23010617
TI  - The role of biologic mesh in abdominal wall reconstruction: a systematic review
      of the current literature.
AB  - BACKGROUND: Biologic mesh in the form of allograft or xenograft products have
      been used in complicated abdominal hernia repair, but few comparative studies
      exist. METHODS: A systematic review of original incisional hernia studies was
      conducted to include 2 primary end points: hernia recurrence and surgical site
      occurrence. Analysis of variance and a Satterthwaite t test compared the devices.
      RESULTS: Twenty-nine studies were included in this analysis, which included 1,257
      patients. The total number of studies and the total subjects for each device
      include the following: Permacol (Tissue Science Laboratories, Hampshire, UK)
      (4/64), Surgisis (Cook Medical, Bloomington, IN) (3/87), and Alloderm (LifeCell,
      Corp, Branchburg, NJ) (23/1,106). Device-specific recurrence rates and surgical
      site occurrence rates, respectively, were as follows: Alloderm (20.8%, 31.4%),
      Permacol (10.9%, 25%), and Surgisis (8.0%, 40.2%). A Satterthwaite t test
      comparison revealed significantly higher numbers of hernia recurrence (P = .006)
      and surgical site occurrence (P = .04) when comparing Alloderm with Permacol.
      CONCLUSIONS: Biologic mesh does play a beneficial role in abdominal wall
      reconstruction although allograft acellular dermal matrix does have a higher
      recurrence rate as compared with xenograft products, which limits its current
      role in hernia repair.

PMID- 23010618
TI  - The autologous normothermic ex vivo perfused porcine liver-kidney model:
      improving the circuit's biochemical and acid-base environment.
AB  - BACKGROUND: The ex vivo porcine liver perfused model isolates the organ from
      extrinsic regulatory mechanisms, facilitating an improved understanding of the
      organ physiology and reaction to various conditions. We have assessed the
      influence of the addition of a porcine kidney to the circuit. METHODS: Eight
      livers were harvested and perfused for 6 hours. In 5 additional experiments a
      kidney also was connected in parallel. Hourly arterial blood gases were collected
      to analyze glucose, acid base, and renal parameters. The primary end point was an
      evaluation of the influence of the kidney on glucose, pH, and electrolyte levels.
      RESULTS: In the combined porcine liver-kidney circuit all the parameters
      significantly improved compared with the liver circuit alone. This was
      particularly evident for glucose values because normoglycemia was reached by the
      end of the perfusion, and for pH and electrolyte values that were maintained at
      initial levels. CONCLUSIONS: The addition of a porcine kidney to the perfusion
      circuit improves the biochemical milieu. This might produce more consistent and
      reliable results, particularly during studies requiring a steady-state
      environment.

PMID- 23010619
TI  - Dose reconstruction of di(2-ethylhexyl) phthalate using a simple pharmacokinetic
      model.
AB  - BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP), used primarily as a plasticizer
      for polyvinyl chloride, is found in a variety of products. Previous studies have
      quantified human exposure by back calculating intakes based on DEHP metabolite
      concentrations in urine and by determining concentrations of DEHP in exposure
      media (e.g., air, food, dust). OBJECTIVES: To better understand the timing and
      extent of DEHP exposure, we used a simple pharmacokinetic model to "reconstruct"
      the DEHP dose responsible for the presence of DEHP metabolites in urine. METHODS:
      We analyzed urine samples from eight adults for four DEHP metabolites [mono(2
      ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5
      oxohexyl) phthalate, and mono(2-ethyl-5-carboxypentyl) phthalate]. Participants
      provided full volumes of all voids over 1 week and recorded the time of each void
      and information on diet, driving, and outdoor activities. Using a model
      previously calibrated on a single person self-dosed with DEHP in conjunction with
      the eight participants' data, we used a simple trial-and-error method to
      determine times and doses of DEHP that resulted in a best fit of predicted and
      observed urinary concentrations of the metabolites. RESULTS: The average daily
      mean and median reconstructed DEHP doses were 10.9 and 5.0 ug/kg-day,
      respectively. The highest single modeled dose of 60 ug/kg occurred when one study
      participant reported consuming coffee and a bagel with egg and sausage that was
      purchased at a gas station. About two-thirds of all modeled intake events
      occurred near the time of reported food or beverage consumption. Twenty percent
      of the modeled DEHP exposure occurred between 2200 hours and 0500 hours.
      CONCLUSIONS: Dose reconstruction using pharmacokinetic models-in conjunction with
      biomonitoring data, diary information, and other related data-can provide a
      powerful means to define timing, magnitude, and possible sources of exposure to a
      given contaminant.

PMID- 23010621
TI  - Src kinase signaling mediates estrous behavior induced by 5beta-reduced
      progestins, GnRH, prostaglandin E2 and vaginocervical stimulation in estrogen
      primed rats.
AB  - The progesterone receptor (PR) is a dual function protein that acts in the
      nucleus as a transcriptional factor and at the cytoplasm as a scaffold for the
      Src-MAPK signaling pathway. Several agents lacking affinity for the PR, such as
      5beta-reduced progestins, GnRH or prostaglandin E(2) (PGE(2)) facilitate estrous
      behavior in ovariectomized (ovx), estrogen-primed rats yet their action is
      blocked by the antiprogestin RU486. We hypothesize that these agents act by using
      the PR-Src-mitogen activated protein kinase alternative pathway. To test this
      hypothesis we used PP2, a specific inhibitor of the Src kinase family.
      Intraventricular infusion of 30 MUg of PP2, 30 min before behavioral testing,
      significantly attenuated estrous behaviors induced in estradiol benzoate (E(2)B)
      primed rats by 5beta-dihydroprogesterone (5beta-DHP), 5beta-pregnan-3beta-ol-20
      one (5beta,3beta-Pgl), GnRH, PGE(2) and by manual flank/vaginocervical
      stimulation. These results suggest that the Src signaling system, by activating
      mitogen-activated protein kinases, participates in the facilitation of estrous
      behavior in E(2)B-primed rats induced by agents lacking affinity for the PR.

PMID- 23010622
TI  - Exploration of the in vitro antiviral activity of a series of new pyrimidine
      analogues on the replication of HIV and HCV.
AB  - BACKGROUND: In continuation of our search for new anti-HIV and anti-HCV agents,
      the suggestion, synthesis and structure elucidation of a new series of 2,6
      diamino-4-alkylthio- or (2-benzylhydrazinyl)-5-p-chlorophenylazopyrimidines), 2,6
      diamino-4-(2-benzylhydrazinyl)-5-(aryl-[1,1'-biphenyl]-4-yl)pyrimidines, 2,6
      diamino-4-(aryl)-5-(aryl[1,1'-biphenyl]-4-yl) pyrimidines), 6-(aryl)-1,3-dimethyl
      5-nitro pyrimidine-2,4-dione and 6-amino-4-methoxy-N,N-dimethyl-6-arylpyrimidines
      were described. METHODS: The anti-HIV-1 (strain IIIB) and HIV-2 (strain ROD)
      activity of the newly synthesized pyrimidine analogues was evaluated in vitro in
      human MT-4 cells using the MT-4/MTT assay. Similarly, the same compounds were
      evaluated in vitro for their selective antiviral activity against HCV in the Huh
      5-2 replicon system (type 1b, Con1 strain). RESULTS: None of the tested compounds
      exhibited inhibition of HIV-1 and HIV-2 replication in cell culture. Even though
      many compounds yielded a 50% effective concentration in the HCV replicon system
      with selectivity indexes up to 6.9, none of the compounds matched the selection
      criteria of a selective inhibitor of virus replication in this assay (that is,
      >70% inhibition at concentrations that do not elicit an anti-metabolic effect on
      the host cells). CONCLUSIONS: Structural modification of these compounds might
      optimize their anti-HCV activity by introducing diverse and potent functional
      groups at the pyrimidine backbone, like nitrile residue. Because of the nature of
      the molecules, these new derivatives will also be evaluated for their potential
      anti-HIV activity.

PMID- 23010620
TI  - Estrogenic plant consumption predicts red colobus monkey (Procolobus
      rufomitratus) hormonal state and behavior.
AB  - Numerous studies have examined the effects of anthropogenic endocrine disrupting
      compounds; however, very little is known about the effects of naturally occurring
      plant-produced estrogenic compounds (i.e., phytoestrogens) on vertebrates. To
      examine the seasonal pattern of phytoestrogen consumption and its relationship to
      hormone levels (407 fecal samples analyzed for estradiol and cortisol) and social
      behavior (aggression, mating, and grooming) in a primate, we conducted an 11
      month field study of red colobus (Procolobus rufomitratus) in Kibale National
      Park, Uganda. The percent of diet from estrogenic plants averaged 10.7% (n=45
      weeks; range: 0.7-32.4%). Red colobus fed more heavily on estrogenic Millettia
      dura young leaves during weeks of higher rainfall, and the consumption of this
      estrogenic item was positively correlated to both their fecal estradiol and
      cortisol levels. Social behaviors were related to estradiol and cortisol levels,
      as well as the consumption of estrogenic plants and rainfall. The more the red
      colobus consumed estrogenic plants the higher their rates of aggression and
      copulation and the lower their time spent grooming. Our results suggest that the
      consumption of estrogenic plants has important implications for primate health
      and fitness through interactions with the endocrine system and changes in hormone
      levels and social behaviors.

PMID- 23010623
TI  - Measuring stock and change in the GB countryside for policy--key findings and
      developments from the Countryside Survey 2007 field survey.
AB  - Countryside Survey is a unique large scale long-term monitoring programme
      investigating stock and change of habitats, landscape features, vegetation, soil
      and freshwaters of Great Britain. Repeat field surveys combine policy and
      scientific objectives to provide evidence on how multiple aspects of the
      environment are changing over time, a key goal of international science in the
      face of profound human impacts on ecosystems. Countryside Survey 2007 (CS2007),
      the fifth survey since 1978, retained consistency with previous surveys, whilst
      evolving in line with technological and conceptual advances in the collection and
      integration of data to understand landscape change. This paper outlines
      approaches taken in the 2007 survey and its subsequent analysis and presents some
      of the headline results of the survey and their relevance for national and
      international policy objectives. Key changes between 1998 and 2007 included: a)
      significant shifts in agricultural land cover from arable to grassland,
      accompanied by increases in the area of broadleaved woodland, b) decreases in the
      length of managed hedges associated with agricultural land, as a proportion
      deteriorated to lines of trees and c) increases in the areas and numbers of wet
      habitats (standing open water, ponds) and species preferring wetter conditions
      (1998-2007 and 1978-2007). Despite international policy directed at maintaining
      and enhancing biodiversity, there were widespread decreases in species richness
      in all linear and area habitats, except on arable land, consistent with an
      increase in competitive and late successional species between 1998 and 2007 and
      1978 and 2007. Late successional and competitive species: Stinging nettle (Urtica
      dioica), Hawthorn (Cratageous monogyna) and Bramble (Rubus fruticosus), in the
      top ten recorded species recorded in 2007, all increased between 1998 and 2007.
      The most commonly recorded species in CS (1990, 1998 and 2007) was agricultural
      Ryegrass (Lolium perenne). Increases in both water quality and soil pH were in
      line with policy aimed at addressing previous deterioration of both. Headwater
      streams broadly showed continued improvements in biological quality from 1998 to
      2007, continuing trends seen since 1990. In soils, there were significant
      increases in soil pH between 1998 and 2007 consistent with recovery from
      acidification.

PMID- 23010624
TI  - The influence of beta-cyclodextrin encapsulation on the binding of 2'
      hydroxyflavanone with calf thymus DNA.
AB  - Inclusion complexation of 2'-hydroxyflavanone (2'HF) with beta-cyclodextrin (beta
      CD) was studied, both in solution phase and as solid inclusion complexes, by UV
      visible and fluorescence spectroscopic, scanning electron microscopic and X-ray
      diffractometric techniques. The interaction of 2'HF with calf thymus DNA (ctDNA)
      in the presence and the absence of beta-CD were compared. Fluorescence
      enhancement was observed for 2'HF due to the formation of 1:1 complex with beta
      CD. The structure of 1:1 complex is proposed based on spectral observation,
      molecular modeling and by calculated theoretical bond lengths. The possible mode
      of interaction between 2'HF and DNA was analyzed by molecular modeling method.
      The interaction of 2'HF with calf thymus DNA (ctDNA) was investigated by
      absorption and fluorescence measurements in the presence and the absence of beta
      CD as capping agent. Both in the presence and the absence of beta-CD, 2'HF showed
      hyper-chromic effect, red shift of absorption spectra, and quenching of
      fluorescence due to binding of 2'HF with ctDNA. The results reveal that the
      phenolic moiety is involved in inclusion complexation with beta-CD and
      interaction with DNA. In the presence of beta-CD, the phenolic moiety may be
      included in cyclodextrin cavity, whereas the dihydrobenzopyran-4-one moiety
      interacts with DNA. Further, beta-CD selectively blocks a part of the 2'HF
      molecule binding with DNA. This renders the remaining portion of the flavanone
      available for interaction with DNA.

PMID- 23010625
TI  - High-pressure resonance Raman spectroscopic study of ultramarine blue pigment.
AB  - The resonance Raman spectrum of ultramarine has been studied as a function of
      pressure up to 5 GPa. The overtone progressions of the nu(1) fundamental and the
      combination bands of S(3)(-) and the nu(1) band of S(2)(-) were measured and the
      pressure dependences were determined. The symmetric stretching mode of S(3)(-) is
      nearly harmonic. No phase transition was observed over the measured pressure
      range.

PMID- 23010626
TI  - Monomer- and polymer radicals of vinyl compounds: EPR and DFT studies of
      geometric and electronic structures in the adsorbed state.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was applied to study the
      paramagnetic species formed from styrene, 1,1-diphenylethylene, alpha
      methylstyrene, beta-methylstyrene and methylmethacrylate adsorbed on amorphous
      silica gel after gamma-irradiation at 77K. Radicals formed by the hydrogen atom
      addition at the vinyl group of the monomers were observed in all samples. The
      hydrogen atoms were shown to originate to a large extent from the adsorbent by
      using silica gel with deuterated silanol groups. An EPR spectrum assigned to a
      propagating radical was observed at increased temperature for samples containing
      methylmethacrylate (MMA). The structures of the adsorption complexes, the
      respective hyperfine splitting constants and the adsorption energies were
      calculated by applying DFT quantum chemical methods. The reaction between an MMA
      molecule and the MMA radical and the structure of the propagating radical was
      modeled. The calculated hyperfine splitting constants for all radicals confirmed
      the assignment of the experimental spectra.

PMID- 23010627
TI  - Malva parviflora extract assisted green synthesis of silver nanoparticles.
AB  - Five plant leaf extracts (Malva parviflora, Beta vulgaris subsp. Vulgaris,
      Anethum graveolens, Allium kurrat and Capsicum frutescens) were screened for
      their bioreduction behavior for synthesis of silver nanoparticles. M. parviflora
      (Malvaceae) was found to exhibit the best reducing and protecting action in terms
      of synthesis rate and monodispersity of the prepared silver nanoparticles. Our
      measurements indicate that biosynthesis of Ag nanoparticles by M. parviflora
      produces Ag nanoparticles with the diameters in the range of 19-25 nm. XRD
      studies reveal a high degree of crystallinity and monophasic Ag nanoparticles of
      face-centered cubic structure. FTIR analysis proved that particles are reduced
      and stabilized in solution by the capping agent that is likely to be proteins
      secreted by the biomass. The present process is an excellent candidate for the
      synthesis of silver nanoparticles that is simple, easy to perform, pollutant free
      and inexpensive.

PMID- 23010628
TI  - Synthesis, spectroscopic characterization and crystal structure of novel NNNN
      donor MU-bis(bidentate) tetraaza acyclic Schiff base ligands.
AB  - Novel NNNN-donor MU-bis(bidentate) tetraaza acyclic Schiff base ligands with
      different substituents (CF(3), N(CH(3))(2) or OH groups) were synthesized by the
      condensation reaction of triethylenetetramine with 4-substituted benzaldehydes.
      Triethylenetetramine tris(4-trifluoromethylbenzylidene) (TTFMB),
      triethylenetetramine tris(4-dimethylaminobenzylidene) (TTDMB) and
      triethylenetetramine tris(2,4-dihydroxybenzylidene) (TTDHB) were formed as N(4)
      donor ligands. The formation of a five-membered imidazolidine ring from the
      ethylenediamine backbone as a spacer-cumbridging unit gives rise to a new type of
      imidazolidine ligand. The structure of the TTFMB and TTDMB were determined by
      single crystal X-ray crystallography. The synthesized ligands have been
      characterized on the basis of the results of cyclic voltammetry (CV) and
      spectroscopic studies viz. FT-IR spectroscopy (FT-IR), mass spectroscopy (MS) and
      UV-Vis spectroscopy (UV-Vis).

PMID- 23010629
TI  - Density functional study of stereo-chemistry and chiroptics of helical alkynyl
      cyclophanes with binaphthyls.
AB  - Stereo-chemistry and chiroptics of several alkynyl cyclophanes with multiple
      binaphthyls are investigated using density functional calculations. It is
      revealed that the lower-energy Cotton effects of tetragon-shape cyclophanes
      originate from electronic transitions on two long sides while the higher-energy
      Cotton effects have important origin in electronic transitions on two short
      sides. According to spectral characteristic and relative energy, we deduce that
      two low-energy conformers of S5 with two meta-position-substituted benzene rings
      are likely to coexist. For S6 as a macrocyclic molecule including eight
      binaphthyls, we infer that only one conformer as S6c is populated. This conformer
      is of a groove-shape structure with the alphabetaalphabeta orientation of four
      meta-position-substituted benzene rings.

PMID- 23010630
TI  - Size dependent electron-phonon coupling in N, Li, In, Ga, F and Ag doped ZnO thin
      films.
AB  - Polarized micro-Raman measurements are performed to study the phonon modes of N,
      Li, In, Ga, F and Ag doped ZnO thin films, grown by spray pyrolysis on corning
      glass substrates. The E(2)(high) mode displays a visible asymmetric line shape.
      The size and dopant dependence onto coupling strength between electron and LO
      phonon is experimentally estimated.

PMID- 23010631
TI  - Brain natriuretic peptide: a relevant marker to rule out delayed atrial
      fibrillation in stroke patient.
AB  - Detection of new atrial fibrillation (AF) after ischemic stroke is challenging.
      The aim of the TARGET-AF study was to identify relevant markers for ruling out
      delayed AF in stroke patients. Early and prolonged Holter electrocardiography
      (ECG) monitoring during hospitalization was performed systematically in
      consecutive acute stroke patients naive to AF (no history of AF or no AF on
      baseline ECG). All clinical and paraclinical data for routine etiologic
      assessment were collected. The diagnostic value of all parameters significantly
      associated with AF was assessed by comparison of area under the receiver
      operating characteristic curve (AUC). Of the 300 stroke patients enrolled (mean
      age, 62.5 +/- 15.5 years; sex ratio: 1.7; mean National Institutes of Health
      Stroke Scale score, 7.1 +/- 7.9, median duration of Holter ECG monitoring, 6.8
      days), 52 (17.3%) had newly diagnosed AF. Parameters significantly associated
      with AF were classified by increasing AUC: anterior circulation localization
      (AUC, 0.604; 95% confidence interval [CI], 0.546-0.660), P-wave initial force
      (AUC, 0.608; 95% CI, 0.545-0.669), left atrial dilatation (AUC, 0.657; 95% CI,
      0.600-0.711), National Institutes of Health Stroke Scale score (AUC, 0.667; 95%
      CI, 0.611-0.720), sex (AUC, 0.683; 95% CI, 0.627-0.736), age (AUC, 0.755; 95% CI,
      0.707-0.797), CHA2DS2-VASc score (AUC, 0.796; 95% CI, 0.746-0.841), STAF (score
      for the targeting of AF) score (AUC, 0.842; 95% CI, 0.796-0.882), and plasma
      brain natriuretic peptide (BNP) level (AUC, 0.868; 95% CI, 0.825-0.904). The use
      of all parameters combined (AUC, 0.910; 95% CI, 0.872-0.940) was not
      significantly more efficient in diagnosing AF than BNP alone (P = .248). At the
      Youden plot, the diagnostic properties for BNP >131 pg/mL were sensitivity, 98.1%
      (95% CI, 89.7-99.7); specificity, 71.4% (95% CI, 65.3-76.9); and negative
      predictive value, 99.4% (95% CI, 96.9-99.9). Our data indicate that a BNP level
      <= 131 pg/mL might rule out delayed AF in stroke survivors and could be included
      in algorithms for AF detection.

PMID- 23010632
TI  - Targeting IRF4 in autoimmune diseases.
AB  - As a member of the IRF family of transcription factors, interferon regulatory
      factor 4 (IRF4) is expressed in most cell types of the immune system. Recent
      findings suggest that IRF4 is essential for the development and function of T
      helper (Th) cell, regulatory T (Treg) cell, B cell, as well as dendritic cell
      (DC). Since these cells are crucial in the pathogenesis of autoimmune diseases,
      such as systemic lupus erythematosus, multiple sclerosis, inflammatory bowel
      disease (Crohn's disease and ulcerative colitis), and type I diabetes, the roles
      of IRF4 in the initiation and progression of autoimmune diseases can not be
      neglected. In this review, we summarize recent advances on the pathological roles
      of IRF4 in autoimmunity and discuss the therapeutic significance of these new
      findings.

PMID- 23010633
TI  - Do integrated care pathways have a place in critical care?
AB  - PURPOSE OF REVIEW: Recent high-profile campaigns have endeavoured to improve the
      quality of critical care provision. Within other specialities, integrated care
      pathways (ICPs) have been advocated as an effective means of improving practice.
      We review the published research regarding their efficacy and potential role in
      critical care. RECENT FINDINGS: ICPs have been used in many specialities to good
      effect, reducing morbidity, increasing adherence to practice guidelines and
      improving multidisciplinary communication and efficiency. Many aspects of ICPs
      are already used in critical and perioperative care. SUMMARY: ICPs show promise
      as a mechanism for improving efficiency and care quality in specific
      circumstances. However, little research specific to critical care has been
      undertaken and it may be challenging to protocolize the multisystem care required
      in many critical illnesses. Although further evaluation is required to find the
      most appropriate way of incorporating ICPs into critical care, we commend their
      thoughtful adoption.

PMID- 23010634
TI  - Structure and function:  planning a new ICU to optimize patient care.
AB  - PURPOSE OF REVIEW: To survey the recent medical literature reporting effects of
      ICU design on patients' and family members' well being, safety and functionality.
      RECENT FINDINGS: Features of ICU design linked to the needs of patients and their
      family are single rooms, privacy, quiet surrounding, exposure to daylight, views
      of nature, prevention of infection, a family area and open visiting hours. Other
      features such as safety, working procedures, ergonomics and logistics have a
      direct impact on the patient care and the nursing and medical personnel. SUMMARY:
      An organization structured on the needs of the patient and their family is
      mandatory in designing a new ICU. The main aims in the design of a new department
      should be patient-centered care, safety, functionality, innovation and a future
      proof concept.

PMID- 23010635
TI  - Protocoled resuscitation and the prevention of acute kidney injury.
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) occurrence in critically ill
      patients is common and is associated with a substantial increase in morbidity and
      mortality. The scope of this review is to summarize the most recent evidence
      based knowledge for prevention of AKI. RECENT FINDINGS: Recent recommendations
      for prevention of AKI in ICU patients are all 'negative' and, similarly, the most
      recent and updated guidelines about major topic areas of interest for AKI,
      including definition and classification, prevention, and pharmacologic treatment,
      have failed to identify single evidence-based recommendations for prevention and
      treatment of AKI. Therefore, the evaluation and management of AKI should be
      guided by clinical algorithms aiming to protocolized hemodynamic optimization,
      metabolic control, monitoring of intra-abdominal hypertension, use of diuretics
      to control fluid overload, and careful management of nephrotoxic factors.
      SUMMARY: Key components of optimal AKI prevention include maintenance of renal
      perfusion and avoidance of precipitating factors. Adequate renal blood flow
      maintenance is the first strategy to employ not only to assure renal oxygenation,
      but also to prevent nephrotoxic drugs-associated AKI. Many potential therapies
      and interventions are on the horizon, but most of the future research will need
      to focus more on a step-wise, protocoled, kidney-oriented approach, than on
      single treatments.

PMID- 23010636
TI  - The pathophysiology of trauma-induced coagulopathy.
AB  - PURPOSE OF REVIEW: Transfusion paradigms and protocols have evolved at a rapid
      pace in the last few years to ameliorate the adverse effects of trauma-induced
      coagulopathy (TIC). This has occurred despite fragmented and inadequate knowledge
      of the underlying pathophysiology that they are supposed to treat. This review
      will collate and assimilate the most recent data about TIC in order to present
      our state-of-the-art understanding of this condition. RECENT FINDINGS: TIC was
      conventionally construed simply as depletion, dysfunction or dilution of
      procoagulant factors. However, contemporary understanding recognizes it as an
      imbalance of the dynamic equilibrium between procoagulant factors, anticoagulant
      factors, platelets, endothelium and fibrinolysis. The endogenous component of TIC
      (acute traumatic coagulopathy) is not merely a consumptive coagulopathy, but is
      characterized by isolated factor V inhibition, dysfibrinogenaemia, systemic
      anticoagulation, impaired platelet function and hyperfibrinolysis. Acute
      traumatic coagulopathy then becomes exacerbated by hypothermia, acidosis and
      resuscitation with hypocoagulable fluids. SUMMARY: Further improvement in the
      outcome from trauma-haemorrhage is possible with more refined and tailored
      haemostatic resuscitation. Achieving this will depend upon a better understanding
      of the haemostatic defects that develop after injury.

PMID- 23010637
TI  - Adjustment to vision loss in a mixed sample of adults with established visual
      impairment.
AB  - PURPOSE: To determine factors associated with the level of adjustment to vision
      loss in a cross-sectional sample of adults with mixed visual impairment. METHODS:
      One hundred participants were administered the Acceptance and Self-Worth
      Adjustment Scale (AS-WAS) to assess adjustment to vision loss. The severity of
      vision loss was determined using binocular clinical visual function assessments
      including visual acuity, contrast sensitivity, reading performance, and visual
      fields. Key demographics including age, duration of visual impairment, general
      health, education, and living arrangements were evaluated, as were self-reported
      vision-related activity limitation (VRAL), depression, social support, and
      personality. RESULTS: Multivariate analysis showed that higher levels of
      depressive symptoms (beta = -0.26, P < 0.01) and of the personality trait
      neuroticism (beta = -0.33, P < 0.001), and lower levels of the personality trait
      of conscientiousness (beta = 0.29, P < 0.01), were associated with poorer
      adjustment to vision loss, explaining 56% variance. CONCLUSIONS: Adjustment to
      vision loss is significantly associated with depression and certain traits of
      personality (specifically neuroticism and conscientiousness), independent of the
      severity of vision loss, VRAL, and duration of vision loss. The results suggest
      certain individuals may be predisposed to exhibiting less adjustment to vision
      loss due to personality characteristics, and exhibit poorer adjustment owing to
      or as a consequence of depression, rather than due to other factors such as the
      onset and severity of visual impairment.

PMID- 23010638
TI  - The effects of transforming growth factor-beta2 on the expression of follistatin
      and activin A in normal and glaucomatous human trabecular meshwork cells and
      tissues.
AB  - PURPOSE: To compare follistatin (FST) and activin (Act) expression in normal and
      glaucomatous trabecular meshwork (TM) cells and tissues and determine if
      exogenous TGF-beta2 regulates the expression of FST and Act in TM cells. METHODS:
      Total RNA was isolated from TM cell strains, and mRNA expression for FST 317/344
      isoforms and Act was determined via RT-PCR and quantitative PCR (qPCR). Western
      immunoblotting and immunocytochemistry determined FST and Act A protein levels in
      normal TM (NTM) and glaucomatous TM (GTM) cells. Cells were treated with
      recombinant human TGF-beta2 protein at 0 to 10 ng/mL for 0 to 72 hours. qPCR,
      Western immunoblotting, immunocytochemistry, and ELISA immunoassay were utilized
      to determine changes in FST and Act A mRNA and protein levels. In addition, NTM
      and GTM tissue samples were examined by immunohistochemistry for expression of
      FST, FST 315, FST 288, and Act A. RESULTS: Both FST mRNA and protein levels were
      significantly elevated in GTM cells. FST mRNA transcripts FST 317/344 were also
      significantly elevated in GTM cells. Immunohistochemistry showed FST levels were
      significantly elevated in GTM tissues. Exogenous TGF-beta2 significantly induced
      FST mRNA and protein expression. Immunohistochemistry demonstrated that Act A
      protein levels were significantly higher in NTM tissues compared to GTM tissues.
      CONCLUSIONS: FST is elevated in GTM cells and tissues. FST is known to be an
      inhibitor of bone morphogenetic proteins (BMPs), which, coupled with the ability
      of TGF-beta2 to upregulate FST levels, may indicate a possible role of FST in the
      pathogenesis of glaucoma. These results suggest that additional endogenous
      molecules in human TM may regulate TGF-beta2 signaling via inhibition of BMP
      family members.

PMID- 23010640
TI  - Sign-dependent sensitivity to peripheral defocus for myopes due to aberrations.
AB  - PURPOSE: Animal studies suggest that the periphery of the eye plays a major role
      in emmetropization. It is also known that human myopes tend to have relative
      peripheral hyperopia compared to the foveal refraction. This study investigated
      peripheral sensitivity to defocus in human subjects, specifically whether myopes
      are less sensitive to negative than to positive defocus. METHODS: Sensitivity to
      defocus (logMAR/D) in the 20 degrees  nasal visual field was determined in 16
      emmetropes (6 males and 10 females, mean spherical equivalent -0.03 +/- 0.13 D,
      age 30 +/- 10 years) and 16 myopes (3 males and 13 females, mean spherical
      equivalent -3.25 +/- 2 D, age 25 +/- 6 years) using the slope of through-focus
      low-contrast resolution (10%) acuity measurements. Peripheral wavefront
      measurements at the same angle were obtained from 13 of the myopes and 9 of the
      emmetropes, from which the objective depth of field was calculated by assessing
      the area under the modulation transfer function (MTF) with added defocus. The
      difference in depth of field between negative and positive defocus was taken as
      the asymmetry in depth of field. RESULTS: Myopes were significantly less
      sensitive to negative than to positive defocus (median difference in sensitivity
      0.06 logMAR/D, P = 0.023). This was not the case for emmetropes (median
      difference -0.01 logMAR/D, P = 0.382). The difference in sensitivity between
      positive and negative defocus was significantly larger for myopes compared to
      emmetropes (P = 0.031). The correlation between this difference in sensitivity
      and objective asymmetry in depth of field due to aberrations was significant for
      the whole group (R(2) = 0.18, P = 0.02) and stronger for myopes (R(2) = 0.8, P <
      0.01). CONCLUSIONS: We have shown that myopes, in general, are less sensitive to
      negative than to positive defocus, which can be linked to their aberrations. This
      finding is consistent with a previously proposed model of eye growth that is
      driven by the difference between tangential and radial peripheral blur.

PMID- 23010639
TI  - Ultraviolet radiation-induced cataract in mice: the effect of age and the
      potential biochemical mechanism.
AB  - PURPOSE: To study the effect of age on the morphologic and biochemical
      alterations induced by in vivo exposure of ultraviolet radiation (UV). METHODS:
      Young and old C57BL/6 mice were exposed to broadband UVB+UVA and euthanized after
      2 days. Another batch of UV-exposed young mice was monitored for changes after 1,
      2, 4, and 8 days. Age-matched nonexposed mice served as controls. Lens changes
      were documented in vivo by slit-lamp biomicroscopy and dark field microscopy
      photographs ex vivo. Lens homogenates were analyzed for glutathione (GSH) level,
      and the activities of thioredoxin (Trx), thioltransferase (TTase), and
      glyceraldehyde-3-phosphate dehydrogenase (G3PD). Glutathionylated lens proteins
      (PSSGs) were detected by immunoblotting using GSH antibody. Western blot analysis
      was also done for the expression levels of TTase and Trx. RESULTS: Both age
      groups developed epithelial and superficial anterior subcapsular cataract at 2
      days postexposure. The lens GSH level and G3PD activity were decreased, and PSSGs
      were elevated in both age groups, but more prominent in the older mice. TTase and
      Trx activity and protein expression were elevated only in the young mice.
      Interestingly, lens TTase and Trx in the young mice showed a transient increase,
      peaking at 2 days after UV exposure and returning to baseline at day 8,
      corroborated by lens transparency. CONCLUSIONS: The lenses of old mice were more
      susceptible to UV radiation-induced cataract. The upregulated TTase and Trx
      likely provided oxidation damage repair in the young mice.

PMID- 23010641
TI  - Upregulation of retinal neuronal MCP-1 in the rodent model of diabetic
      retinopathy and its function in vitro.
AB  - PURPOSE: To  evaluate the expression of monocyte chemoattractant protein-1 (MCP
      1) in the rodent model of diabetic retinopathy (DR) and to study the stimulation
      of microglial activation by retinal neuronal MCP-1 in vitro. METHODS: Diabetes
      mellitus was induced by streptozotocin (STZ) injection. The expression of MCP-1
      was determined using immunohistochemical methods, Western blotting and RT-PCR
      analyses. Retinal neurons and microglia were separated and co-cultured in a
      Transwell apparatus. The levels of soluble MCP-1 that were produced after
      stimulation of retinal neurons by adding advanced glycation end products (AGEs)
      to the medium were measured by ELISA. The degree of microglial activation was
      measured by testing microglial migration and the level of soluble TNF-alpha in
      the medium by ELISA. The ability of neuronal MCP-1 to stimulate microglia
      activation was examined by pre-exposing the retinal neurons to AGEs and an MCP-1
      antibody or to AGEs and SiRNA specific to MCP-1. RESULTS: A marked increase in
      the expression of MCP-1 was detected 4 weeks after STZ injection, and the
      expression was consistently upregulated at 3 and 5 months in the rodent DR model.
      Stimulation with AGEs significantly increased the expression of MCP-1 in retinal
      neurons, which activated microglial cells, including increased microglial
      migration and upregulated secretion of TNF-alpha. Retinal neurons that were pre
      exposed to AGEs and an MCP-1 antibody or MCP-1 knockdown displayed greatly
      reduced microglial migration and TNF-alpha secretion. CONCLUSIONS: Upregulation
      of MCP-1 began during the early stage of DR and increased with the development of
      the disease. Retinal neurons are the main source of MCP-1, and they play an
      important role in retinal microglial activation, which may be an important link
      in the pathogenesis of DM.

PMID- 23010642
TI  - Methylation of the polycomb group target genes is a possible biomarker for
      favorable prognosis in colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in the
      Kingdom of Saudi Arabia with ever increasing incidence rates. DNA methylation is
      a common event in CRC where it is now considered an important phenomenon in CRC
      carcinogenesis and useful for the classification and prognosis of CRC. METHODS:
      To gain insight into the molecular mechanisms underpinning CRC in Saudi Arabian
      patients, we profiled the DNA methylation frequency of key genes (MLH1, MSH2,
      RASSF1A, SLIT2, HIC1, MGMT, SFRP1, MYOD1, APC, CDKN2A, as well as five CIMP
      markers) in 120 sporadic CRC cases. CRC tumors originating from the rectum, left,
      and right colons are represented in this cohort of formalin-fixed paraffin
      embedded tissues. RESULTS: The most common methylation frequency was detected in
      the polycomb group target genes (PCGT) including SFRP1 (70%), MYOD1 (60.8%), HIC1
      (61.7%), and SLIT2 (56.7%). In addition, MGMT methylation was detected at a high
      frequency (68.3%). RASSF1A, APC, and CDKN2A methylation frequencies were 42.5%,
      25%, and 32.8%, respectively. K-means clustering analysis of the methylation
      events results in the clustering of the CRC samples into three groups depending
      on the level of methylation detected. CONCLUSION: Group II (PCGT methylation and
      CIMP-negative) methylation signature carried a favorable prognosis for male
      patients, whereas older patients with group I rare methylation signature have a
      potentially poorer clinical outcome. IMPACT: Methylation of the PCGT genes along
      with RASSF1A, APC, and MGMT can be potentially used as a new biomarker for the
      classification and prognosis of CRC tumors and independently of where the tumor
      has originated.

PMID- 23010643
TI  - Bile acid promotes intestinal metaplasia and gastric carcinogenesis.
AB  - BACKGROUND: Bile acid and Helicobacter pylori (H. pylori) are important toxic
      factors for gastric mucosal injury. We examined the role of bile acid in
      promoting histologic gastritis and gastric carcinoma in Japanese patients.
      METHODS: A total of 767 patients (452 men, mean age 51.1 years) were studied.
      Gastric juice was collected by gastro-endoscopic examination, and the bile acid
      concentration was examined by enzymatic method. The grade of histologic gastritis
      was evaluated by gastric biopsies, and the relationship between the bile acid
      concentration and the gastritis score was examined. The occurrence of gastric
      cancer was examined by a retrospective cohort study. CDX2/CINC1 expression in RGM
      1 cells was evaluated by real-time PCR. RESULTS: In H. pylori-positive patients,
      we found significant positive correlation between the bile acid concentration and
      the grades of atrophy/intestinal metaplasia (P < 0.01). However, we found
      significant negative associations between the bile acid concentrations and the
      histologic scores of mononuclear cell/neutrophil infiltrations (P < 0.01).
      Patients with a high concentration of bile acid developed gastric cancer more
      frequently than those with a low concentration (P < 0.05). Cholic acid treatment
      significantly increased CDX2 expression in RGM-1 cells. CINC1 expression in RGM-1
      cell was significantly induced by coculture with H. pylori, and the induction was
      reduced by glycochenodeoxycholic acid treatment. CONCLUSION: The bile acid in
      gastric juice contributes to the progression of histologic atrophy and intestinal
      metaplasia without inflammatory cell infiltration, followed by carcinogenesis in
      H. pylori-positive patients. IMPACT: Bile acid promotes intestinal metaplasia and
      gastric carcinogenesis without inflammatory cell infiltration.

PMID- 23010644
TI  - Fibroregulation of mesenchymal progenitor cells by BMP-4 after traumatic muscle
      injury.
AB  - OBJECTIVES: Traumatized muscle is a complex healing environment containing cells
      with robust reparative and regenerative potential interacting in a cytokine
      milieu that influences the function and differentiation of these cells, leading
      to a spectrum of healing responses. In particular, bone morphogenetic protein-4
      (BMP-4) is of interest as a potential modulator of healing because its
      dysregulation has been associated with fibrosis and heterotopic ossification
      formation. We propose a descriptive study of altered BMP-4 expression in
      traumatized muscle tissue and to evaluate its role in the fibroregulatory
      function of resident mesenchymal progenitor cells (MPCs) at the protein- and gene
      expression levels. METHODS: Protein-level expression of BMP-4 from cells resident
      in traumatized muscle specimens was evaluated using ELISA and also using sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis to compare BMP-4 in
      homogenized muscle tissue specimens. BMP-4, cartilage oligomeric matrix protein
      (COMP), and osteocalcin expression localization was analyzed via
      immunohistochemistry. Reverse transcription-polymerase chain reaction was
      performed to evaluate fibroregulatory gene expression in MPCs after treatment
      with BMP-4. RESULTS: BMP-4 was present in all traumatized muscle tissue
      specimens. Immunohistochemistry demonstrated that traumatized muscle fibers
      contained greater number of cells expressing BMP-4 in a more disorganized fashion
      compared with control samples. Reverse transcription-polymerase chain reaction
      demonstrated that COMP, growth and differentiation factor-10, and integrin beta-2
      were up-regulated, whereas tumor necrosis factor-alpha was significantly down
      regulated. COMP expression was colocalized in the traumatized muscle tissue with
      osteocalcin. CONCLUSIONS: BMP-4 has an effect on MPCs that seems to promote
      fibrotic tissue formation. These findings suggest that BMP-4, while promoting
      osteoinduction, may also act on MPCs to promote formation of a fibrotic
      osteoinductive matrix. Thus, this signaling axis might be a potential target for
      heterotopic ossification prevention.

PMID- 23010645
TI  - Pre- and postoperative function after scapula malunion reconstruction: a novel
      kinematic technique.
AB  - This report describes a novel kinematic analysis technique that was used to
      assess a floating shoulder malunion before and after corrective osteotomy. The
      patient underwent this analysis pre- and postoperatively using electromagnetic
      motion sensors and monitoring software. Pre- and postoperative motion curves were
      compared with normal subject data to determine if shoulder girdle movement was
      more or less similar to subjects without any shoulder pathology. Additionally,
      strength, range of motion, and patient-based questionnaires, including DASH and
      SF-36, were obtained. The preoperative DASH score was 30 and decreased to 3 in 18
      months after surgery. Kinematic analysis demonstrated improved postoperative
      resting position of the scapula and motion patterns more consistent with healthy
      subject data.

PMID- 23010646
TI  - Mesenchymal stem cells facilitate fracture repair in an alcohol-induced impaired
      healing model.
AB  - OBJECTIVES: Clinical studies have shown alcohol to be a risk factor for traumatic
      orthopaedic injuries and for nonunion. Data from animal studies suggest that
      alcohol exposure inhibits fracture healing. This report presents a novel rodent
      model of impaired fracture healing caused by repeated alcohol exposure. Using
      this model, we examined the regenerative effects of an intravenously administered
      population of isolated and expanded mesenchymal stem cells (MSCs) on fracture
      healing. METHODS: Bone marrow-derived MSC were isolated from transgenic green
      fluorescent protein C57BL/6 mice, and culture expanded using a lineage depletion
      protocol. Adult wild-type C57BL/6 mice were subjected to a 2-week binge alcohol
      exposure paradigm (3 days during which they received daily intraperitoneal
      injections of a 20% alcohol/saline solution followed by a 4-day rest period and
      another binge cycle for 3 consecutive days). At completion of the second binge
      cycle, mice were subjected to a mid-shaft tibia fracture while intoxicated.
      Twenty-four hours after the fracture, animals were administered an intravenous
      transplant of green fluorescent protein-labeled MSC. Two weeks after the
      fracture, animals were euthanized and injured tibiae were collected and subjected
      to biomechanical, histologic, and microcomputed tomography analysis. RESULTS: Pre
      injury binge alcohol exposure resulted in a significant impairment in
      biomechanical strength and decrease in callus volume. MSC transplants restored
      both fracture callus volume (P < 0.05) and biomechanical strength (P < 0.05) in
      animals with alcohol-impaired healing. In vivo imaging demonstrated a time
      dependent MSC migration to the fracture site. CONCLUSIONS: These data suggest
      that a 2-week binge alcohol exposure significantly impairs fracture healing in a
      murine tibia fracture model. Intravenously administered MSC were capable of
      specifically homing to the fracture site and of normalizing biomechanical,
      histologic, and microcomputed tomography parameters of healing in animals exposed
      to alcohol. Understanding MSC recruitment patterns and functional contributions
      to fracture repair may lead to their use in patients with impaired fracture
      healing and nonunion.

PMID- 23010647
TI  - Designing a biomechanics investigation:  choosing the right model.
AB  - Physical testing is commonly performed to answer important biomechanical
      questions in the treatment of patients with fractures and other orthopaedic
      conditions. However, a variety of mistakes that are made in performing such
      investigations can severely limit their impact. The goal of this article is to
      discuss important aspects of study design to consider when planning for
      biomechanical investigations so that the studies can provide maximal benefit to
      the field. The best mechanical investigations begin with a good research
      question, one that comes out of patient care experience, is clearly defined, and
      can be stated concisely. The first practical issue to be considered is often
      choosing the type of physical specimens to be tested to address the research
      question. A related issue involves determining how many specimens will be needed
      to answer the posed mechanical question. Cadavers are generally still the closest
      to the actual clinical situation, but they are limited by interspecimen
      variability, which often requires a matched pair design that can address only one
      question. Simulated bone specimens limit variability and can replicate normal and
      osteoporotic bone. In planning the physical testing, the critical mechanical
      variables involved in answering the research question must be identified and due
      consideration given to deciding how best to measure them. Another important issue
      that arises relates to whether or not single static loadings will suffice in the
      testing (eg, to study construct stiffness) or whether cyclic dynamic testing is
      necessary (eg, to study late failure likely attributable to fatigue). To
      summarize, experimental design should be carefully planned before initiating
      mechanical testing. Sample size calculations should be performed to ensure
      adequate power and that clinically relevant differences can be detected. This
      pregame analysis can save significant time and cost and greatly increase the
      likelihood that the results will advance knowledge.

PMID- 23010648
TI  - Heterotopic ossification in orthopaedic trauma.
AB  - Heterotopic ossification (HO) can be defined as the pathologic formation of bone
      in extraskeletal tissues. There has been a substantial amount of recent research
      on the pathophysiology, prophylaxis, and treatment of HO and traumatic conditions
      associated with the development of HO. This research has advanced our
      understanding of this disease and helped to clarify evidence-based approaches to
      both the prophylaxis and treatment of HO. This article reviews the literature on
      these topics with a focus on their application in orthopaedic trauma.

PMID- 23010649
TI  - Use of healthy volunteers drives clinical oncology drug development decision
      making.

PMID- 23010650
TI  - Contribution of the OATP1B subfamily to cancer biology and treatment.

PMID- 23010651
TI  - Computational modeling to accelerate the identification of substrates and
      inhibitors for transporters that affect drug disposition.

PMID- 23010652
TI  - Hepatocyte hopping of OATP1B substrates contributes to efficient hepatic
      detoxification.

PMID- 23010653
TI  - Multi-biomarker responses in fishes from two typical marine aquaculture regions
      of South China.
AB  - The impact of typical pollutants upon the fish-farming was assessed by use of a
      battery of biomarkers in two typical marine aquaculture regions in South China.
      Biotransformation parameters including 7-ethoxyresorufin-O-deethylase (EROD),
      aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND), glutathione
      S-transferase (GST) and Malondialdehyde (MDA) were measured in five cultured fish
      species. Pollutants such as polycyclic aromatic hydrocarbon (PAHs),
      organochlorinated compounds (OCs), heavy metals and antibiotics (quinolones and
      sulfonamides) in sediments were characterized. Higher pollutant residue levels
      were observed in Dapeng Cove. EROD, APND and ERND activities were lower in fish
      from Dapeng Cove compared with fish from Hailing Island, while it is just on the
      contrary for GST and MDA. ERND, APND and GST showed sensitivity corresponding to
      different pollutants. Small fish species seemed to exhibit more sensitive to
      pollutants. The study further supports usefulness of multi-biomarker approach
      considering multiple species to define the effects of anthropogenic inputs in
      marine aquaculture systems.

PMID- 23010654
TI  - Photosynthetic response of two seaweed species along an urban pollution gradient:
      evidence of selection of pollution-tolerant species.
AB  - Urbanization leads to the expansion of ephemeral seaweed species and the decline
      of important perennial, canopy-forming seaweed species. Understanding the
      mechanisms that lead to these changes is a current challenge. In the present
      study, laboratory assays and field transplantations were performed with two
      seaweed species: the perennial, canopy-forming seaweed Sargassum stenophyllum and
      the ephemeral seaweed Ulva lactuca. Photosynthetic efficiency was assessed using
      modulated chlorophyll fluorometry. Brief exposure to urban waters does not appear
      to be a major stressor to the photosynthetic efficiency of either species.
      However, after 26 days of transplantation in urban waters, S. stenophyllum
      declined, whereas U. lactuca had enhanced photosynthetic efficiency. This
      difference reflects their divergent abilities to regulate the energy distribution
      at the PSII and shows that urban stressors alter these mechanisms. Our results
      provide evidence of the physiological causes for the decline of Sargassum species
      and the expansion of Ulva species in impacted urban areas.

PMID- 23010655
TI  - Gold nanoparticles-catalyzed activation of 1,2-disilanes: hydrolysis, silyl
      protection of alcohols and reduction of tert-benzylic alcohols.
AB  - Gold nanoparticles supported on TiO(2) catalyze under mild conditions the
      activation of a series of 1,2-disilanes towards hydrolysis and alcoholysis, with
      concomitant evolution of H(2) gas. For the case of tert-benzyl alcohols, the main
      or only pathway is reduction to the corresponding alkanes.

PMID- 23010657
TI  - Cellular circadian clocks in mood disorders.
AB  - Bipolar disorder (BD) and major depressive disorder (MDD) are heritable
      neuropsychiatric disorders associated with disrupted circadian rhythms. The
      hypothesis that circadian clock dysfunction plays a causal role in these
      disorders has endured for decades but has been difficult to test and remains
      controversial. In the meantime, the discovery of clock genes and cellular clocks
      has revolutionized our understanding of circadian timing. Cellular circadian
      clocks are located in the suprachiasmatic nucleus (SCN), the brain's primary
      circadian pacemaker, but also throughout the brain and peripheral tissues. In BD
      and MDD patients, defects have been found in SCN-dependent rhythms of body
      temperature and melatonin release. However, these are imperfect and indirect
      indicators of SCN function. Moreover, the SCN may not be particularly relevant to
      mood regulation, whereas the lateral habenula, ventral tegmentum, and
      hippocampus, which also contain cellular clocks, have established roles in this
      regard. Dysfunction in these non-SCN clocks could contribute directly to the
      pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non
      SCN clocks is a trait marker of mood disorders, encoded by pathological genetic
      variants. Because network features of the SCN render it uniquely resistant to
      perturbation, previous studies of SCN outputs in mood disorders patients may have
      failed to detect genetic defects affecting non-SCN clocks, which include not only
      mood-regulating neurons in the brain but also peripheral cells accessible in
      human subjects. Therefore, reporters of rhythmic clock gene expression in cells
      from patients or mouse models could provide a direct assay of the molecular gears
      of the clock, in cellular clocks that are likely to be more representative than
      the SCN of mood-regulating neurons in patients. This approach, informed by the
      new insights and tools of modern chronobiology, will allow a more definitive test
      of the role of cellular circadian clocks in mood disorders.

PMID- 23010656
TI  - Hyaluronan activation of the Nlrp3 inflammasome contributes to the development of
      airway hyperresponsiveness.
AB  - BACKGROUND: The role of the Nlrp3 inflammasome in nonallergic airway
      hyperresponsiveness (AHR) has not previously been reported. Recent evidence
      supports both interleukin (IL) 1beta and short fragments of hyaluronan (HA) as
      contributors to the biological response to inhaled ozone. OBJECTIVE: Because
      extracellular secretion of IL-1beta requires activation of the inflammasome, we
      investigated the role of the inflammasome proteins ASC, caspase1, and Nlrp3 in
      the biological response to ozone and HA. METHODS: C57BL/6J wild-type mice and
      mice deficient in ASC, caspase1, or Nlrp3 were exposed to ozone (1 ppm for 3 hr)
      or HA followed by analysis of airway resistance, cellular inflammation, and total
      protein and cytokines in bronchoalveolar lavage fluid (BALF). Transcription
      levels of IL-1beta and IL-18 were determined in two populations of lung
      macrophages. In addition, we examined levels of cleaved caspase1 and cleaved IL
      1beta as markers of inflammasome activation in isolated alveolar macrophages
      harvested from BALF from HA-treated mice. RESULTS: We observed that genes of the
      Nlrp3 inflammasome were required for development of AHR following exposure to
      either ozone or HA fragments. These genes are partially required for the cellular
      inflammatory response to ozone. The expression of IL-1beta mRNA in alveolar
      macrophages was up-regulated after either ozone or HA challenge and was not
      dependent on the Nlrp3 inflammasome. However, soluble levels of IL-1beta protein
      were dependent on the inflammasome after challenge with either ozone or HA. HA
      challenge resulted in cleavage of macrophage-derived caspase1 and IL-1beta,
      suggesting a role for alveolar macrophages in Nlrp3-dependent AHR. CONCLUSIONS:
      The Nlrp3 inflammasome is required for the development of ozone-induced reactive
      airways disease.

PMID- 23010659
TI  - Sympatric Drosophilid species melanogaster and ananassae differ in temporal
      patterns of activity.
AB  - The fruit fly Drosophila melanogaster has long served as a model system for
      circadian rhythm research. Various aspects of its genetic, molecular, and circuit
      level properties are the subject of investigation, based on which several
      circadian behaviors and their neuronal controls have been unraveled. In an
      attempt to address the question of functional significance of circadian
      organization using a comparative approach, we studied activity/rest rhythm of
      wild-caught D. melanogaster (DM) and its close relative, Drosophila ananassae
      (DA). We compared features of the rhythm such as the ability to anticipate
      morning and evening transitions, presence or absence of morning-associated or
      evening-associated activity peaks, and phase of these peaks in both species. We
      found that these 2 sympatric species are different from each other in several
      aspects of activity/rest rhythm. Unlike DM, which showed a distinct bimodal
      activity pattern with both morning and evening peaks and a midday interval of
      relative inactivity under a 12:12-h light/dark regime, DA exhibited unimodal
      activity with a predominant morning peak, restricting most of its activity to the
      light phase with no apparent "siesta" during midday. While daytime sleep levels
      were not different between the 2 species, DA exhibited significantly lesser
      nighttime activity and higher, more consolidated sleep. This predominant morning
      activity of DA was also reflected in persistence and phasing of the morning peak
      under a range of photoperiods. Both under long and short days, the morning peak
      was the most dominant and persistent peak of DA, whereas the evening peak was
      more dominant in DM. In addition, DA had a significantly faster circadian clock
      and more consolidated activity compared with DM. Hence, we hypothesize that these
      recently diverged sympatric species of fruit flies occupy distinct temporal
      niches due to differences in their underlying circadian clocks and speculate that
      they occupy different spatial microenvironments in the wild.

PMID- 23010658
TI  - A mechanism for circadian control of pacemaker neuron excitability.
AB  - Although the intracellular molecular clocks that regulate circadian (~24 h)
      behavioral rhythms are well understood, it remains unclear how molecular clock
      information is transduced into rhythmic neuronal activity that in turn drives
      behavioral rhythms. To identify potential clock outputs, the authors generated
      expression profiles from a homogeneous population of purified pacemaker neurons
      (LN(v)s) from wild-type and clock mutant Drosophila. They identified a group of
      genes with enriched expression in LN(v)s and a second group of genes rhythmically
      expressed in LN(v)s in a clock-dependent manner. Only 10 genes fell into both
      groups: 4 core clock genes, including period (per) and timeless (tim), and 6
      genes previously unstudied in circadian rhythms. The authors focused on one of
      these 6 genes, Ir, which encodes an inward rectifier K(+) channel likely to
      regulate resting membrane potential, whose expression peaks around dusk. Reducing
      Ir expression in LN(v)s increased larval light avoidance and lengthened the
      period of adult locomotor rhythms, consistent with increased LN(v) excitability.
      In contrast, increased Ir expression made many adult flies arrhythmic and
      dampened PER protein oscillations. The authors propose that rhythmic Ir
      expression contributes to daily rhythms in LN(v) neuronal activity, which in turn
      feed back to regulate molecular clock oscillations.

PMID- 23010660
TI  - Flies in the north: locomotor behavior and clock neuron organization of
      Drosophila montana.
AB  - The circadian clock plays an important role in adaptation in time and space by
      synchronizing changes in physiological, developmental, and behavioral traits of
      organisms with daily and seasonal changes in their environment. We have studied
      some features of the circadian activity and clock organization in a northern
      Drosophila species, Drosophila montana, at both the phenotypic and the neuronal
      levels. In the first part of the study, we monitored the entrained and free
      running locomotor activity rhythms of females in different light-dark and
      temperature regimes. These studies showed that D. montana flies completely lack
      the morning activity component typical to more southern Drosophila species in an
      entrained environment and that they are able to maintain their free-running
      locomotor activity rhythm better in constant light than in constant darkness. In
      the second part of the study, we traced the expression of the PDF neuropeptide
      and the CRY protein in the neurons of the brain in D. montana adults and found
      differences in the number and location of PDF- and CRY-expressing neurons
      compared with those described in Drosophila melanogaster. These differences could
      account, at least in part, for the lack of morning activity and the reduced
      circadian rhythmicity of D. montana flies in constant darkness, both of which are
      likely to be adaptive features during the long and dark winters occurring in
      nature.

PMID- 23010661
TI  - Time of day changes in cyclic nucleotides are modified via octopamine and
      pheromone in antennae of the Madeira cockroach.
AB  - The cockroach Rhyparobia (Leucophaea) maderae expresses a circadian rhythm in
      pheromone-dependent mating activity that peaks at the late day/early night. In
      contrast, the circadian rhythm in olfactory sensitivity of the Madeira cockroach
      is at its minimum during this time. Until now, the reasons for this obvious
      discrepancy in phase were not understood. Previously, it was shown that cyclic
      nucleotides modulate olfactory sensitivity in a zeitgeber time (ZT)-dependent
      manner. In moths' olfactory receptor neurons, adapting pheromone concentrations
      elevate cGMP levels, which decrease pheromone sensitivity. In contrast, cAMP
      elevations sensitized pheromone responses. Thus, with immunoassay kits, it was
      determined whether cAMP and cGMP baseline levels vary in a ZT-dependent manner in
      antennal lysates of female R. maderae, revealing underlying circadian rhythms in
      olfactory sensitivity. Furthermore, it was examined whether adapting pheromone
      exposure elevates cGMP levels in cockroach antennae, possibly overshadowing
      underlying circadian rhythms in sensitivity via sensory adaptation. It was shown
      for the first time that cAMP and cGMP baseline levels oscillate in antiphase in a
      ZT-dependent manner in an insect's antenna, with the maximum in cAMP
      concentrations coinciding with maximal mating activity during the late day.
      Moreover, the cAMP baseline level oscillation expressed a circadian rhythm since
      it persisted under constant darkness in contrast to cGMP baseline levels.
      Furthermore, while excess exposure to male pheromones increased cGMP and
      decreased cAMP baseline levels, the stress hormone octopamine increased adenylyl
      cyclase activity at all ZTs tested. Therefore, it is suggested that cyclic
      nucleotide-dependent modulation of olfactory sensitivity due to olfactory
      overstimulation and stress could be responsible for previously measured phase
      discrepancies between rhythms in mating behavior and pheromone sensitivity.

PMID- 23010662
TI  - Dopamine is involved in food-anticipatory activity in mice.
AB  - When food is available during a restricted and predictable time of the day,
      mammals exhibit food-anticipatory activity (FAA), an increase in locomotor
      activity preceding the presentation of food. Although many studies have attempted
      to locate the food-entrainable circadian oscillator in the central nervous
      system, the pathways that mediate food entrainment are a matter of controversy.
      The present study was designed to determine the role of dopaminergic and
      histaminergic systems on FAA. Mice were given access to food for 2 h (ZT12-ZT14),
      and FAA was defined as the locomotor activity that occurred 2 h before the
      availability of food. Dopamine D(1) receptor (R), D(2)R, and histamine H(1)R
      specific antagonists were used to clarify the role of dopamine and histamine
      receptors in FAA induced by food restriction (FR). FAA was monitored by infrared
      locomotor activity sensors. Mice were sacrificed at ZT12 on the 14th day of FR,
      and monoamine concentrations were determined by high-performance liquid
      chromatography coupled to electrochemical detection (HPLC-ECD). The results
      showed that pretreatment with the D(1)R antagonist SCH23390 at 1, 3, or 10 ug/kg
      significantly reduced FAA by 19% (p < 0.05), 26% (p < 0.05), or 19% (p < 0.01),
      respectively, and the D(2)R antagonist raclopride at 22, 67, or 200 ug/kg
      significantly reduced FAA by 16% (p < 0.05), 36% (p < 0.01), or 41% (p < 0.01),
      respectively, as compared with vehicle control. Moreover, coadministration of
      SCH23390 (10 ug/kg) and raclopride (200 ug/kg) synergistically inhibited FAA by
      57% (p < 0.01) as compared with vehicle control. Consistently, the levels of
      dopamine and its metabolites in the striatum and midbrain were significantly
      increased during FAA, even with the pretreatment of D(1)R and D(2)R antagonists.
      However, pretreatment with pyrilamine at 2.5, 5, or 10 mg/kg did not
      significantly reduce FAA, although it reduced the locomotor activity during the
      dark period in ad libitum mice. These results strongly indicate that the
      dopaminergic system plays an essential role in the FAA in mice.

PMID- 23010663
TI  - Individual differences in circadian waveform of Siberian hamsters under multiple
      lighting conditions.
AB  - Because the circadian clock in the mammalian brain derives from a network of
      interacting cellular oscillators, characterizing the nature and bases of
      circadian coupling is fundamental to understanding how the pacemaker operates.
      Various phenomena involving plasticity in circadian waveform have been theorized
      to reflect changes in oscillator coupling; however, it remains unclear whether
      these different behavioral paradigms reference a unitary underlying process. To
      test whether disparate coupling assays index a common mechanism, we examined
      whether there is covariation among behavioral responses to various lighting
      conditions that produce changes in circadian waveform. Siberian hamsters,
      Phodopus sungorus, were transferred from long to short photoperiods to
      distinguish short photoperiod responders (SP-R) from nonresponders (SP-NR). Short
      photoperiod chronotyped hamsters were subsequently transferred, along with
      unselected controls, to 24-h light:dark:light: dark cycles (LDLD) with dim
      nighttime illumination, a procedure that induces bifurcated entrainment. Under
      LDLD, SP-R hamsters were more likely to bifurcate their rhythms than were SP-NR
      hamsters or unselected controls. After transfer from LDLD to constant dim light,
      SP-R hamsters were also more likely to become arrhythmic compared to SP-NR
      hamsters and unselected controls. In contrast, short photoperiod chronotype did
      not influence more transient changes in circadian waveform. The present data
      reveal a clear relationship in the plasticity of circadian waveform across 3
      distinct lighting conditions, suggesting a common mechanism wherein individual
      differences reflect variation in circadian coupling.

PMID- 23010665
TI  - Automated quantitative 3D analysis of faceting of particles in tomographic
      datasets.
AB  - Characterization of facets of particles is a common problem. In this paper an
      algorithm is presented which allows automated quantitative 3D analysis of facets
      of many particles within tomographic datasets. The algorithm is based on the
      analysis of probability distributions of the orientations of triangle normals of
      mesh representations. The result consists of lists containing number of detected
      facets, their size, global orientation and the interplanar angles between facets
      for each analyzed particle. Characterization of each particle according to any of
      these facet properties is then possible, e.g. statistics about different crystal
      shapes or removal of particles that do not show significant faceting. Analyses of
      a 3D dataset obtained by focused ion beam (FIB) tomography of a sample containing
      spinel particles are presented.

PMID- 23010666
TI  - The feasibility of caseload midwifery in rural Australia: a literature review.
AB  - BACKGROUND: Caseload midwifery is a continuity of care(r) model being implemented
      in an increasing number of Australian maternity settings. Question for review: is
      caseload midwifery a feasible model for introducing into the rural Australian
      context? METHOD: Integrative literature review. FINDINGS: Four main categories
      were identified and these include the evidence for caseload midwifery;
      applicability to the rural context; experiences of registered and student
      midwives and implementation of caseload midwifery models. CONCLUSION: There is
      evidence to support caseload midwifery and its implementation in the rural
      setting. However, literature to date is limited by small participant size and
      possible selection bias. Further research, including rural midwives' expectations
      and experience of caseload midwifery may lead to improved sustainability of
      midwifery care for rural Australian women.

PMID- 23010667
TI  - A model of primary and scattered photon fluence for mammographic x-ray image
      quantification.
AB  - We present an efficient method to calculate the primary and scattered x-ray
      photon fluence component of a mammographic image. This can be used for a range of
      clinically important purposes, including estimation of breast density,
      personalized image display, and quantitative mammogram analysis. The method is
      based on models of: the x-ray tube; the digital detector; and a novel ray tracer
      which models the diverging beam emanating from the focal spot. The tube model
      includes consideration of the anode heel effect, and empirical corrections for
      wear and manufacturing tolerances. The detector model is empirical, being based
      on a family of transfer functions that cover the range of beam qualities and
      compressed breast thicknesses which are encountered clinically. The scatter
      estimation utilizes optimal information sampling and interpolation (to yield a
      clinical usable computation time) of scatter calculated using fundamental physics
      relations. A scatter kernel arising around each primary ray is calculated, and
      these are summed by superposition to form the scatter image. Beam quality,
      spatial position in the field (in particular that arising at the air-boundary due
      to the depletion of scatter contribution from the surroundings), and the possible
      presence of a grid, are considered, as is tissue composition using an iterative
      refinement procedure. We present numerous validation results that use a purpose
      designed tissue equivalent step wedge phantom. The average differences between
      actual acquisitions and modelled pixel intensities observed across the adipose to
      fibroglandular attenuation range vary between 5% and 7%, depending on beam
      quality and, for a single beam quality are 2.09% and 3.36% respectively with and
      without a grid.

PMID- 23010668
TI  - Spontaneous self-assembly of partially fluorinated bolaamphiphiles into ordered
      layered structures.
AB  - We developed a simple method for preparation of well-defined films of X-, T- and
      anchor-shaped bolaamphiphiles. The compounds were judiciously chosen to
      investigate the influence of the general molecular structure on the self-assembly
      properties. Precisely calculated (on the basis of Langmuir pi(A) isotherms)
      volumes of chloroform solutions of the compounds of known concentrations were
      spread (drop-casted) directly onto the surface of water or silicon wafer. During
      the solvent evaporation, regular thin films were spontaneously formed. With use
      of the drop-casting (DC) method, films of thickness of up to three molecular
      layers could be obtained. X-ray reflectivity (XRR) measurements gave insight into
      arrangement of the molecules within the films. Different models of molecular
      organisation in the films were confronted with the experimental results. Advanced
      fitting procedures allowed for precise determination of the structure of the
      films. Comparison of films of different compounds obtained using different
      methods (Langmuir-Blodgett, DC) allowed for a deeper insight into the process of
      self-assembly, providing guidelines for designing functional molecules
      spontaneously forming thin, regular films. The proposed DC procedure is a novel
      alternative to broadly used self-assembled monolayers (SAMs). Unlike SAMs, our
      method does not require specific molecule-surface interactions and allows
      formation of films thicker than a monolayer.

PMID- 23010670
TI  - Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.
AB  - Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were
      evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots
      of peripheral venous human blood were incubated with tarragon extract, saline, or
      the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose
      were electrophoresed in ethidium bromide. The resulting DNA migration trails were
      obtained using fluorescent microscopy at 400* magnification, and graded according
      to the mutagenicity index (MI) for each cell incubation condition. The in vivo
      liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated
      orally with the extract of the herb, using alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) as liver function indicators. Liver morphology
      was assessed using hematoxylin and eosin (HE) staining of liver tissue. The
      present study demonstrated a direct correlation between tarragon extract dosage
      and three major outcome variables: MI; serum liver enzyme activity; and liver
      histopathology. These outcomes are possibly due to the presence in tarragon of
      methylchavicol and other genotoxic compounds. These findings provide a
      preliminary guide for risk assessment of tarragon in diet and in possible
      therapeutic applications.

PMID- 23010671
TI  - Beyond survival: recommendations from INTERMACS for assessing function and
      quality of life with mechanical circulatory support.

PMID- 23010672
TI  - Photophysical properties of iminopyrrolyl boron complexes: a DFT interpretation.
AB  - The three compounds [BPh(2)(kappa(2)N,N'-NC(4)H(3)C(H)=N-C(6)H(5))] (A),
      [BPh(2)(kappa(2)N,N'-NC(4)H(3)C(H)=N-1,4-C(6)H(4)-N=H)C-H(3)C(4)N
      N,N'kappa(2))BPh(2)] (B) and [BPh(2)(kappa(2)N,N'-NC(4)H(3)C(H)=N-4,4'-C(6)H(4)
      C(6)H(4)-N=(H)C-H(3)C(4)N-N,N'kappa(2))BPh(2)] (C) are blue to green light
      emitters with average to excellent quantum yields. DFT and TD-DFT calculations
      were performed in order to understand their behaviour. The geometry of their
      ground and singlet excited state was optimised, and their absorption patterns and
      emission were calculated. The large dihedral angles between the planes of the N
      aryl and 2-formiminopyrrolyl moieties of the chelating ligand drop considerably,
      leading to an almost planar geometry in the singlet state. In the three species,
      the lowest energy absorption occurs at 383, 428, and 419 nm, being calculated at
      377, 502, and 529 nm in the gas-phase (slightly shifted in the right direction in
      THF). It results from a HOMO to LUMO excitation, and was assigned to a transition
      between pi and pi* orbitals (ILCT) of the iminopyrrolyl ligand, despite small
      differences in the exact composition of the HOMO and LUMO in A, B, and C.
      Introduction of the LB94 functional did not improve the calculated absorption
      wavelengths, but PBE0 with an all electron basis set within the SOPERT
      approximation led to better agreement with the experimental absorption maxima and
      a good reproduction of the excited state lifetimes. The estimated emission
      wavelengths reproduce the experimental trends.

PMID- 23010673
TI  - Evaluation of a modified extraction protocol increasing sensitivity in
      quantification of CMV viremia in Guthrie cards.

PMID- 23010674
TI  - Monitoring brain repair in stroke using advanced magnetic resonance imaging.

PMID- 23010675
TI  - Poststroke hypertension in Africa.
AB  - BACKGROUND AND PURPOSE: Little is known about the frequency of hypertension and
      related knowledge in Africans who have had a stroke. The objective of this study
      was to determine the frequency of hypertension, its control, and associated
      knowledge among patients with and without a history of stroke at Uganda's main
      referral hospital. METHODS: Subjects with a history of stroke (n=157) were
      compared with stroke-free control subjects (n=149). Demographics and clinical
      characteristics were recorded and hypertension-related knowledge assessed by
      questionnaire. Multiple logistic regression including cases and control subjects
      was used to determine factors independently associated with blood pressure
      control and hypertension-related knowledge. RESULTS: A total of 69.4% of cases
      versus 54.7% of control subjects were hypertensive at the time of the research
      visit (P=0.001). Univariable analyses showed the odds of having good blood
      pressure control (OR, 0.53; 95% CI, 0.33-0.84; P=0.006) and good hypertension
      knowledge (OR, 0.35; 95% CI, 0.22-0.56; P<0.0001) were lower in cases. Age <40
      years (P=0.002), good hypertension-related knowledge (P=0.002), and poorer
      medication adherence (P<0.0001) were independently associated with poorer blood
      pressure control. Those with a history of hypertension had better hypertension
      related knowledge (P=0.001), but knowledge was poorer among cases (P<0.0001).
      CONCLUSIONS: Hypertension is common in Ugandans with and without a history of
      stroke. Barriers to effective blood pressure control in Uganda other than patient
      knowledge need to be identified.

PMID- 23010676
TI  - Validating the stroke-thrombolytic predictive instrument in a population in the
      United kingdom.
AB  - BACKGROUND AND PURPOSE: This study aimed to test the explanatory qualities of the
      Stroke-Thrombolytic Predictive Instrument (S-TPI) when applied to patients
      treated in routine practice. METHODS: S-TPI predictions were compared with
      observed outcomes in terms of normal/near-normal (modified Rankin Scale score,
      <=1) and catastrophic outcome (modified Rankin Scale score, >=5) at 3 months.
      Logistic regression was used to calibrate and expand the S-TPI. RESULTS: The S
      TPI overestimated probability of catastrophic outcomes and overestimated the
      probability of a normal/near normal outcome above 0.4 and underestimated those
      below. Calibrating the S-TPI minimized discrepancies between predicted and
      observed outcomes, in the case of normal/near-normal outcomes, where including
      additional predictors (serum glucose and signs of current infarction on
      pretreatment brain scan) further reduced discrepancies between predicted and
      observed outcomes. CONCLUSIONS: The explanatory power of the S-TPI in
      thrombolytic-treated patients can be improved to reflect outcomes seen in routine
      practice.

PMID- 23010677
TI  - Identification of a genetic variant common to moyamoya disease and intracranial
      major artery stenosis/occlusion.
AB  - BACKGROUND AND PURPOSE: The c.14576G>A variant in ring finger protein 213
      (RNF213) was recently identified as a susceptibility gene variant for moyamoya
      disease (MMD). The occurrence of c.14576G>A variant was evaluated in patients
      with intracranial major artery stenosis/occlusion (ICASO) without signs of MMD
      (non-MMD ICASO), as well as in patients with MMD and other cerebrovascular
      diseases as controls. METHODS: This single-hospital-based case-control study was
      completed in 7 months (from October 2011-April 2012) at Department of
      Neurosurgery, The University of Tokyo Hospital. The occurrence of c.14576G>A
      variant was analyzed in 41 patients with non-MMD ICASO, in 48 with MMD, in 21
      with cervical disease, in 61 with cerebral aneurysm, and in 25 normal subjects.
      RESULTS: Nine of 41 patients (21.9%) with non-MMD ICASO and 41 of 48 (85.4%) with
      MMD had the c.14576G>A variant. One of 61 patients (1.6%) with cerebral aneurysm
      and no patients with cervical disease or normal subjects had the variant.
      Comparison of each phenotype group with the normal subjects showed that presence
      of c.14576G>A variant had significant associations with MMD (odds ratio [OR],
      292.8; 95% confidence interval [CI], 15.4-5153.0; P<0.0001) and with non-MMD
      ICASO (OR, 14.9; 95% CI, 0.82-268.4; P=0.01), but no association with either
      cerebral aneurysm (OR, 1.2; 95% CI, 0.04-32.0; P=1.00) or cervical disease (OR,
      1.1; 95% CI, 0.02-62.3; P=1.00). CONCLUSIONS: The present study indicates that a
      particular subset of Japanese patients with non-MMD ICASO has a genetic variant
      associated with MMD. Therefore, we propose the existence of a new entity of ICASO
      caused by the c.14576G>A variant in RNF213.

PMID- 23010678
TI  - Will delays in treatment jeopardize the population benefit from extending the
      time window for stroke thrombolysis?
AB  - BACKGROUND AND PURPOSE: Pooled analyses show benefits of intravenous alteplase
      (recombinant tissue-type plasminogen activator) treatment for acute ischemic
      stroke up to 4.5 hours after onset despite marketing approval for up to 3 hours.
      However, the benefit from thrombolysis is critically time-dependent and if
      extending the time window reduces treatment urgency, this could reduce the
      population benefit from any extension. METHODS: Based on 3830 UK patients
      registered between 2005 to 2010 in the Safe Implementation of Treatments in
      Stroke-International Stroke Thrombolysis Registry (SITS-ISTR), a Monte Carlo
      simulation was used to model recombinant tissue-type plasminogen activator
      treatment up to 4.5 hours from onset and assess the impact (numbers surviving
      with little or no disability) from changes in hospital treatment times associated
      with this extended time window. RESULTS: We observed a significant relation
      between time remaining to treat and time taken to treat in the UK SITS-ISTR data
      set after adjustment for censoring. Simulation showed that as this "deadline
      effect" increases, an extended treatment time window entails that an increasing
      number of patients are treated at a progressively lower absolute benefit to a
      point where the population benefit from extending the time window is entirely
      negated. CONCLUSIONS: Despite the benefit for individual patients treated up to
      4.5 hours after onset, the population benefit may be reduced or lost altogether
      if extending the time window results in more patients being treated but at a
      lower absolute benefit. A universally applied reduction in hospital arrival to
      treatment times of 8 minutes would confer a population benefit as large as the
      time window extension.

PMID- 23010679
TI  - On communication between gut microbes and the brain.
AB  - PURPOSE OF REVIEW: Interest in the microbiota-gut-brain axis is increasing apace
      and what was, not so long ago, a hypothetical relationship is emerging as a
      potentially critical factor in the regulation of intestinal and mental health.
      Studies are now addressing the neural circuitry and mechanisms underlying the
      influence of gut bacteria on the central nervous system and behavior. RECENT
      FINDINGS: Gut bacteria influence development of the central nervous systems (CNS)
      and stress responses. In adult animals, the overall composition of the microbiota
      or exposure to specific bacterial strains can modulate neural function,
      peripherally and centrally. Gut bacteria can provide protection from the central
      effects of infection and inflammation as well as modulate normal behavioral
      responses. Behavioral effects described to date are largely related to stress and
      anxiety and an altered hypothalamus-pituitary-adrenal axis response is a common
      observation in many model systems. The vagus nerve has also emerged as an
      important means of communicating signals from gut microbes to the CNS. SUMMARY:
      Studies of microbiota-gut-brain communication are providing us with a deeper
      understanding of the relationship between the gut bacteria and their hosts while
      also suggesting the potential for microbial-based therapeutic strategies that may
      aid in the treatment of mood disorders.

PMID- 23010680
TI  - The impact of gut microbes in allergic diseases.
AB  - PURPOSE OF REVIEW: The prevalence of allergic diseases continues to rise globally
      in developed countries. Since the initial proposal of the hygiene hypothesis,
      there has been increasing evidence to suggest that the intestinal microbiota,
      particularly during early infancy, plays a critical role in regulating immune
      responses associated with the development of atopy. This review evaluates the key
      epidemiologic and mechanistic data published to date. RECENT FINDINGS:
      Epidemiological data have provided the framework for animal studies investigating
      the importance of gut commensals in allergy development. These studies provide
      new insights about the microbial regulation of mucosal immune responses inside
      and outside the gut, and how these effects may drive allergic inflammation in
      susceptible individuals. Specific immune cells have been identified as mediators
      of these microbiota-regulated allergic responses. SUMMARY: In the last year,
      technological advances have provided us with a better understanding of the gut
      microbiome in healthy and allergic individuals. Recent studies have identified
      the associations between particular gut microbes and different disease
      phenotypes, as well as identified immune cells and their mediators involved in
      allergy development. This research has provided a number of host and microbe
      targets that may be used to develop novel therapies suitable for the treatment or
      prevention of allergic diseases.

PMID- 23010681
TI  - Proton pump inhibitors:  potential adverse effects.
AB  - PURPOSE OF REVIEW: This review summarizes adverse effects of potential proton
      pump inhibitors (PPIs), including nutritional deficiencies (B12 and magnesium),
      rebound acid hypersecretion, acute interstitial nephritis, gastric carcinoid
      tumor, cardiovascular risk with clopidogrel and PPI coprescription, bone
      fractures, enteric infections and pneumonia. An epidemiologic framework is
      applied to assess clinical relevance and reinforce best practice recommendations.
      RECENT FINDINGS: The evidence for PPI adverse events is limited by the absence of
      Level 1 (randomized controlled trial) studies. The best evidence supports
      Clostridium difficile and bone fractures in susceptible populations. A
      substantial reduction in gastrointestinal bleeding risk without increase in
      cardiovascular events was observed in the COGENT trial when clopidogrel was
      coprescribed with omeprazole. The risk of pneumonia is inconsistent, and although
      acute interstitial nephritis, nutritional deficiencies (including B12 and
      hypomagnesemia), gastric carcinoid and rebound hyperacidity are biologically
      plausible, studies have failed to demonstrate supportive clinical relevance.
      SUMMARY: Prescribe PPI for robust indications only. Strong data supporting risk
      of adverse events are lacking; however, exercise caution in the elderly and in
      patients with other risk factors for bone fractures or C. difficile infection.

PMID- 23010682
TI  - Helicobacter pylori:  clinical management.
AB  - PURPOSE OF REVIEW: Progress continues in our understanding of the role of
      Helicobacter pylori infection in gastroduodenal as well as extragastric
      disorders. This review gives an overview on selected areas of the H. pylori
      infection and their clinical implications. RECENT FINDINGS: Indications for
      therapy have been extended and now include idiopathic thrombocytopenic purpura,
      iron deficiency anemia, and vitamin B12 deficiency. New data are presented on the
      role of H. pylori in neurodegenerative disorders and in the metabolic syndrome.
      H. pylori is associated with a (small) increase in the risk for colorectal
      adenoma and colon cancer. The biggest challenge is the selection of new therapies
      and treatment strategies because of the increasing failure of standard triple
      therapies. The best option in high clarithromycin resistance areas is bismuth
      based quadruple therapy. Probiotic bacteria and yeasts reduce adverse effects of
      standard H. pylori eradication regimens. In gastric cancer prevention, screening
      programs based on the serological detection of preneoplastic conditions may prove
      useful. SUMMARY: New algorithms for preventing H. pylori-induced disease and
      eradicating the organism should be individualized.

PMID- 23010683
TI  - Current opinion in gastroenterology.

PMID- 23010684
TI  - Drinking and driving in southeastern Brazil: results from a roadside survey
      study.
AB  - OBJECTIVE: The objective of this study is to present data from a roadside survey
      study on drinking and driving and alcohol consumption in southeastern Brazil.
      METHODS: A cross-sectional roadside survey study using a questionnaire and
      breathalyzer data is the method used to determine the prevalence of drinking and
      driving and to examine whether socio-demographic characteristics and drivers'
      behavior, attitude and alcohol consumption predicted positive blood alcohol
      content (BAC). The data were gathered from 2005 to 2007 through roadside surveys
      conducted on high volume public roads in four cities in southeastern Brazil. A
      total of 4182 randomly selected drivers took part in the research. Of these
      drivers, 3488 (83.4%) completed the questionnaire and agreed to take a breath
      test. RESULTS: Overall, 24.6% of drivers had a detectable blood alcohol
      concentration (BAC) and 15.9% had a BAC above the legal limit (0.6g/l) at the
      time of the study. Logistic regression controlling for locale (city), sex, age
      and marital status was used to predict whether each driver would present a
      positive breath test. Socio-demographic characteristics, driving behaviors and
      attitudes, and alcohol consumption patterns were included as predictors. These
      analyses indicated that those who believed drinking and driving was a serious
      offense were about two-thirds as likely to have a positive breath test, and that
      drivers reporting a pattern of regular alcohol use were three times as likely to
      have a positive breath test. CONCLUSIONS: These findings indicate that drinking
      and driving is relatively common in Brazil, and that it occurs considerably more
      frequently than similar surveys suggest, is the case in other countries.

PMID- 23010686
TI  - A proliferation-inducing ligand (APRIL) in neutrophils of patients with oral
      cavity squamous cell carcinoma.
AB  - Available data indicating a role for neutrophils in the tumor-host reactions are
      controversial. In 37 patients with oral cavity squamous cell carcinoma (OSCC), we
      investigated the expression of a tumor-promoting, proliferation-inducing ligand
      (APRIL) molecule by peripheral blood neutrophils isolated from blood samples
      collected at presentation and three weeks after surgery, and the serum levels of
      TGF-beta in the same samples. Additionally, we investigated the consequences of
      TLR4 activation by LPS for the synthesis of APRIL by those cells. The levels of
      mRNA for APRIL and TLR4 were measured using a real-time PCR method. Western blot
      analysis was used to assay the expressions of APRIL and ERK1/2 in cell lysates.
      The results of the present study revealed the unfavorable features of the
      detection, in the blood, of neutrophils displaying an enhanced expression of the
      tumor-promoting APRIL molecule. The increased expression and release of APRIL
      accompanying advanced stages of disease demonstrated by these cells, combined
      with the increased number of neutrophils, may be an important marker of disease
      progression in the patient group examined. Simultaneously, an increased level of
      circulating TGF-beta in the serum of these patients appeared to be associated
      with the overexpression of APRIL in their neutrophils. In contrast to the healthy
      controls, TLR4 expression and the ERK1/2 signaling pathway appear to play only
      minor roles in APRIL induction in the cells of patients with cancer. The changes
      presented in the current study suggest that modulation of the expression of tumor
      promoting APRIL, in addition to TRAIL and BAFF, might be taken into account in
      the development of new strategies for supportive immunotherapy of OSCC disease
      and possibly for other types of neoplasm as well.

PMID- 23010687
TI  - Concomitant use of enteral nutrition therapy is associated with sustained
      response to infliximab in patients with Crohn's disease.
AB  - BACKGROUND/OBJECTIVES: A significant proportion of Crohn's disease (CD) patients
      receiving infliximab (IFX) maintenance therapy show loss of responsiveness
      despite a good initial response. The factors other than immunomodulators that
      prevent IFX dose escalation have yet to be fully elucidated. This study was
      performed to identify clinical factors or concomitant therapies associated with
      sustained response to IFX. SUBJECTS/METHODS: Seventy-four consecutive CD patients
      who had successful IFX induction therapy between 2002 and 2010 underwent IFX
      maintenance therapy. Patients showing loss of response to IFX were treated with
      IFX intensification therapy. Factors involved in the sustained response to IFX
      were investigated retrospectively. RESULTS: After a median follow-up of 85 weeks,
      loss of response to IFX was observed in 30 (40.5%) cases. On logistic regression
      analysis, concomitant use of enteral nutrition (EN) therapy (elemental and/or
      polymeric formulas) was identified as an independent factor associated with
      sustained response to IFX. Receiver operating characteristic curve analysis
      indicated a cutoff value of 600 kcal/day. We divided the patients into the 'EN
      group' (>= 600 kcal/day) and 'control group' (<600 kcal/day). The cumulative
      number of loss of response was significantly lower in the EN group (odds ratio:
      0.23, P = 0.0043). Kaplan-Meier analysis confirmed the significantly lower rate
      of loss of response in the EN group (P = 0.013). Multivariate hazard ratio was
      0.37 (P = 0.025). Type of EN formula did not affect the results. CONCLUSIONS:
      Concomitant use of EN >= 600 kcal/day is likely to yield a sustained response to
      IFX in CD patients.

PMID- 23010685
TI  - Individual and contextual predictors of severity of marijuana use events among
      young frequent users.
AB  - This study used momentary sampling to characterize marijuana events among young
      frequent users and determine contextual and individual predictors of use
      severity. Medical clinic outpatients aged 15-24 who used marijuana at least twice
      a week completed a baseline assessment, then used a handheld computer to report
      marijuana use at 4-6 signal-prompted times per day and before/after use for 2
      weeks. Reports assessed event characteristics (when, with whom, where, how, why,
      how much, how high). Timestamps identified time, weekend, and duration for each
      event. Generalized estimating equations tested associations of individual and
      event-specific contextual characteristics with hits/event, duration, and high.
      Forty-one youth completed 3868 momentary reports; 40 (98%) reported at least one
      marijuana use event (N=432 events; M=10.5/participant) and thus provided data for
      these analyses. Marijuana was most commonly used with other people (74% of
      events), at home (58%), via blunt (66%), and for social or enhancement reasons
      (86%). Most events (62%) occurred on weekdays; use was least likely in the
      morning (8%). Most events involved 6 or more hits (81%). Mean high was 5.2 (out
      of 8). Of events with start and end times (n=250), mean duration was 46.8 min.
      Poor mental health and use with a blunt or a bong, in the morning or evening, and
      on the weekend were associated with 6 or more hits/event. Female gender was
      associated with greater event duration. Poor mental health predicted higher high.
      Among youth who used it frequently, marijuana was used in a variety of contexts,
      with diversity in method, dose, and duration. Contextual factors appeared to
      predict marijuana dose for a given event, while individual characteristics were
      more predictive of high and duration.

PMID- 23010688
TI  - Validity of a short diet-quality index to predict changes in anthropometric and
      cardiovascular risk factors: a simulation study.
AB  - Coronary heart disease prevention in the primary care setting, where time is
      extremely limited, requires valid instruments that efficiently screen for
      unhealthy lifestyle habits. Identification of the individuals who would most
      benefit from dietary intervention is particularly important in this context. We
      used dietary intake data derived from a full-length food frequency questionnaire
      to simulate responses to our previously validated short dietary quality screener.
      We determined the prospective association of the resulting diet-quality index
      (DQI) with changes in anthropometric and cardiometabolic risk variables in 2181
      men and women in a 10-year follow-up. Multiple linear regression analyses
      revealed that a higher DQI score at baseline related directly (P=0.002) to high
      density lipoprotein cholesterol (HDL-C) and inversely (P<0.016) to waist
      circumference (WC), triacylglycerides (TG), the TG to HDL-C ratio and the total
      cholesterol to HDL-C ratio at follow-up. A low DQI score is predictive for an
      increase in WC and the development of an unfavourable cardiometabolic profile.

PMID- 23010690
TI  - Pulse shape discrimination and classification methods for continuous depth of
      interaction encoding PET detectors.
AB  - In previous work we demonstrated the potential of positron emission tomography
      (PET) detectors with depth-of-interaction (DOI) encoding capability based on
      phosphor-coated crystals. A DOI resolution of 8 mm full-width at half-maximum was
      obtained for 20 mm long scintillator crystals using a delayed charge integration
      linear regression method (DCI-LR). Phosphor-coated crystals modify the pulse
      shape to allow continuous DOI information determination, but the relationship
      between pulse shape and DOI is complex. We are therefore interested in developing
      a sensitive and robust method to estimate the DOI. Here, linear discriminant
      analysis (LDA) was implemented to classify the events based on information
      extracted from the pulse shape. Pulses were acquired with 2*2*20 mm(3) phosphor
      coated crystals at five irradiation depths and characterized by their DCI values
      or Laguerre coefficients. These coefficients were obtained by expanding the
      pulses on a Laguerre basis set and constituted a unique signature for each pulse.
      The DOI of individual events was predicted using LDA based on Laguerre
      coefficients (Laguerre-LDA) or DCI values (DCI-LDA) as discriminant features.
      Predicted DOIs were compared to true irradiation depths. Laguerre-LDA showed
      higher sensitivity and accuracy than DCI-LDA and DCI-LR and was also more robust
      to predict the DOI of pulses with higher statistical noise due to low light
      levels (interaction depths further from the photodetector face). This indicates
      that Laguerre-LDA may be more suitable to DOI estimation in smaller crystals
      where lower collected light levels are expected. This novel approach is promising
      for calculating DOI using pulse shape discrimination in single-ended readout
      depth-encoding PET detectors.

PMID- 23010691
TI  - Beyond delayed cerebral vasospasm: infarct patterns in patients with subarachnoid
      hemorrhage.
AB  - PURPOSE: Angiographic vasospasm (CVS) has been accused to be the main cause of
      delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH).
      However, treatment success including endovascular treatment remains to be
      improved. We performed a pattern analysis of ischemic lesions in SAH patients in
      the absence of angiographic cerebral vasospasm to generate further hypotheses
      concerning etiology and risk factors of DCI apart from vasospastic narrowing.
      METHODS: We retrospectively included 309 patients with cerebral infarcts after
      SAH. Vasospasm was assessed by means of CT or MR angiography and perfusion
      measurement or digital subtraction angiography. All clinical and radiological
      data were used to determine the most probable etiology for new infarcts. RESULTS:
      Twenty-seven percent of patients showed infarcts without presence of angiographic
      vasospasm. Seventy-three percent of these "atypical infarcts" were induced by
      complications of aneurysm therapy, 7 % by hypoxia, 2 % by ICP-related herniation.
      In 17 %, the etiology remained unclear; however, disturbances of the
      microcirculation for different reasons were the most likely cause in these
      patients. CONCLUSION: Beyond CVS and treatment complications, a not insignificant
      number of SAH patients suffered from infarcts of other etiology probably due to
      disturbance of the microcirculation. Therapeutic approaches for vasodilation of
      angiographic vasospasm alone should be reconsidered.

PMID- 23010692
TI  - Lacrimo-auriculo-dento-digital syndrome with unilateral inner ear dysplasia and
      craniocervical osseous abnormalities: case report and review of literature.

PMID- 23010693
TI  - Effect of cued training on motor evoked potential and cortical silent period in
      people with Parkinson's disease.
AB  - OBJECTIVE: To examine whether training under visual cues could enhance motor
      cortical excitability and intracortical inhibition in individuals with
      Parkinson's disease (PD). METHODS: This was a single blinded cross-over study.
      Eight individuals with PD received two sessions of 30-min pinch-grip training
      with and without visual cues. The visual cue was given in form of an arrow that
      indicated the pre-set force level on a computer screen. Outcome measures
      consisted of peak motor evoked potential (MEP) and cortical silent period (CSP)
      of the first dorsal interosseus as well as behavioural tests including Purdue
      pegboard test, tapping speed in 30s, and the maximum pinch grip force exerted by
      the thumb and index finger. RESULTS: After cued training, there were significant
      increases in the peak MEP, CSP duration and tapping speed (all p<0.05). In
      contrast, there was no change in all outcome measures after training under the
      non-cued condition. CONCLUSIONS: Thirty minutes of pinch-grip training with
      visual cues could enhance motor cortical excitability and intracortical
      inhibition in individuals with PD. SIGNIFICANCE: The findings on the
      neurophysiological changes after cued-training may inform further clinical
      application of visual cues to maximize motor improvement and corticomotor
      plasticity in people with PD.

PMID- 23010694
TI  - Stationary wavelet transform and higher order statistical analyses of
      intrafascicular nerve recordings.
AB  - Nerve signals were recorded from the sciatic nerve of the rabbits in the acute
      experiments with multi-channel thin-film longitudinal intrafascicular electrodes.
      5.5 s sequences of quiescent and high-level nerve activity were spectrally
      decomposed by applying a ten-level stationary wavelet transform with the
      Daubechies 10 (Db10) mother wavelet. Then, the statistical distributions of the
      raw and subband-decomposed sequences were estimated and used to fit a fourth
      order Pearson distribution as well as check for normality. The results indicated
      that the raw and decomposed background and high-level nerve activity
      distributions were nearly zero-mean and non-skew. All distributions with the
      frequency content above 187.5 Hz were leptokurtic except for the first-level
      decomposition representing frequencies in the subband between 12 and 24 kHz,
      which was Gaussian. This suggests that nerve activity acts to change the
      statistical distribution of the recording. The results further demonstrated that
      quiescent recording contained a mixture of an underlying pink noise and low-level
      nerve activity that could not be silenced. The signal-to-noise ratios based upon
      the standard deviation (SD) and kurtosis were estimated, and the latter was found
      as an effective measure for monitoring the nerve activity residing in different
      frequency subbands. The nerve activity modulated kurtosis along with SD,
      suggesting that the joint use of SD and kurtosis could improve the stability and
      detection accuracy of spike-detection algorithms. Finally, synthesizing the
      reconstructed subband signals following denoising based upon the higher order
      statistics of the subband-decomposed coefficient sequences allowed us to
      effectively purify the signal without distorting spike shape.

PMID- 23010695
TI  - Enantioselective apoptosis induction in histiocytic lymphoma cells and acute
      promyelocytic leukemia cells.
AB  - The aim of this study was to identify valproic acid (VPA) analogs with a broad
      spectrum of anti-cancer activities and an increased apoptosis-inducing potential
      compared with the parent VPA, which is enrolled as histone deacetylase (HDAC)
      inhibitor in a large number of clinical trials. We identified a chiral VPA
      derivative, (S)-2-pentyl-4-pentynoic acid, previously characterized as HDAC
      inhibitor that induced massive programmed cell death in a strongly
      enantioselective manner in U937 histiocytic lymphoma cells and NB4 acute
      promyelocytic leukemia cells. By performing fluorescence-activated cell sorting
      and Western blotting analyses, we established that enantiomer (S)-2-pentyl-4
      pentynoic acid has higher apoptosis-inducing potential than VPA itself. The optic
      antipode (R)-2-pentyl-4-pentynoic acid and VPA caused under the same conditions
      only a weak growth inhibition without inducing cell differentiation and
      apoptosis. (S)-2-pentyl-4-pentynoic acid is more apoptogenic than VPA and
      displays enantioselective anti-cancer properties that warrant further research
      regarding the mechanistic basis of its activity and its potential use in cancer
      therapy.

PMID- 23010696
TI  - Cost-effectiveness of internet and telephone treatment for smoking cessation: an
      economic evaluation of The iQUITT Study.
AB  - BACKGROUND: Internet and telephone treatments for smoking cessation can reach
      large numbers of smokers. There is little research on their costs and the impact
      of adherence on costs and effects. OBJECTIVE: To conduct an economic evaluation
      of The iQUITT Study, a randomised trial comparing Basic Internet, Enhanced
      Internet and Enhanced Internet plus telephone counselling ('Phone') at 3, 6, 12
      and 18 months. METHODS: We used a payer perspective to evaluate the average and
      incremental cost per quitter of the three interventions using intention-to-treat
      analysis of 30-day single-point prevalence and multiple-point prevalence (MPP)
      abstinence rates. We also examined results based on adherence. Costs included
      commercial charges for each intervention. Discounting was not included given the
      short time horizon. RESULTS: Basic Internet had the lowest cost per quitter at
      all time points. In the analysis of incremental costs per additional quitter,
      Enhanced Internet+Phone was the most cost-effective using both single and MPP
      abstinence metrics. As adherence increased, the cost per quitter dropped across
      all arms. Costs per quitter were lowest among participants who used the 'optimal'
      level of each intervention, with an average cost per quitter at 3 months of US$7
      for Basic Internet, US$164 for Enhanced Internet and US$346 for Enhanced
      Internet+Phone. CONCLUSIONS: 'Optimal' adherence to internet and combined
      internet and telephone interventions yields the highest number of quitters at the
      lowest cost. Cost-effective means of ensuring adherence to such evidence-based
      programmes could maximise their population-level impact on smoking prevalence.

PMID- 23010697
TI  - Safety of CETP inhibition.
AB  - PURPOSE OF REVIEW: Cholesteryl ester transfer protein (CETP)-inhibiting drugs
      effectively raise HDL cholesterol. In 2007, the CETP inhibitor torcetrapib
      unexpectedly showed increased fatality and cardiovascular events, possibly
      related to increased blood pressure and aldosterone levels caused by torcetrapib.
      Since then, novel CETP inhibiting drugs have been investigated. This review will
      discuss the safety of the CETP-inhibiting drugs. RECENT FINDINGS: The novel CETP
      inhibitors dalcetrapib, evacetrapib and anacetrapib did not show harmful effects
      on blood pressure or aldosterone levels. Ultrasound brachial artery flow-mediated
      vasodilation, carotid MRI and (18)F-fluordeoxyglucose PET imaging studies, showed
      that dalcetrapib therapy had neither harmful nor beneficial effects on
      endothelial function, atherosclerosis progression, or vessel wall inflammation.
      Recently, the clinical endpoint study investigating dalcetrapib was announced to
      be terminated early, after the second interim analysis showed that dalcetrapib
      lacked clinically meaningful efficacy. SUMMARY: Dalcetrapib, evacetrapib and
      anacetrapib did not show the harmful effects on aldosterone and blood pressure
      that were exhibited by torcetrapib, indicating that CETP inhibition is well
      tolerated. So far CETP inhibition did not show beneficial effects on clinical
      outcome. The phase III study with anacetrapib will give final answers on whether
      CETP inhibition can reduce cardiovascular events.

PMID- 23010698
TI  - Omega-3 fatty acids and coronary heart disease. The final verdict?
AB  - PURPOSE OF REVIEW: The fish fatty acids eicosapentenoic acid (EPA) and
      docosahexenoic acid (DHA) may be protective against fatal coronary heart disease
      (CHD) and sudden cardiac death. This review summarizes the recent findings of
      prospective cohort studies and randomized controlled trials. RECENT FINDINGS: A
      recently published meta-analysis of 17 prospective cohort studies showed that
      eating fish once a week compared to eating less fish was associated with a 16%
      lower risk of fatal CHD. Epidemiologic studies with cardiac arrest or sudden
      cardiac death as endpoint observed also an inverse relation with fish
      consumption. In contrast, a recently published meta-analysis of 14 randomized,
      double-blind, placebo-controlled trials in cardiovascular patients did not show a
      protective effect of an additional amount of EPA-DHA on fatal CHD and sudden
      cardiac death. Subgroup analyses suggested that this could be because of a low
      absolute risk as a consequence of the state-of-the-art drug treatment. SUMMARY:
      Eating fatty fish once or lean fish twice a week is recommended for both primary
      and secondary prevention of CHD. A definite statement cannot be made about the
      dosage of EPA-DHA required for secondary prevention of CHD.

PMID- 23010699
TI  - Long-term surgical outcomes of patients with type 1 autoimmune pancreatitis.
AB  - BACKGROUND: Although pancreatectomy has sometimes been performed for patients
      with autoimmune pancreatitis (AIP) presenting atypical radiologic findings under
      the diagnosis of pancreatobiliary malignancy, the long-term surgical outcome of
      these patients had not yet been fully elucidated. METHODS: The long-term surgical
      outcomes of 13 patients with pathologically diagnosed type 1 AIP with
      immunohistochemical staining for immunoglobulin G4 (IgG4) were retrospectively
      compared with those of 34 patients with conventional chronic pancreatitis to
      evaluate the residual pancreatic function. RESULTS: A definite relapse of AIP in
      terms of the clinical manifestations and diagnostic imaging was not found in any
      of the patients, although one patient experienced an attack of acute pancreatitis
      caused by pancreatic stones, and stricture of the hepaticojejunostomy occurred in
      one patient. The overall body weight decreased significantly more in patients
      with AIP than in patients with conventional chronic pancreatitis (p < 0.05);
      however, there was no difference in the preoperative nondiabetic patients.
      Refractory diarrhea occurred in only one patient with AIP. The cumulative new
      onset rates of diabetes mellitus of the ten patients with AIP and 24 patients
      with conventional chronic pancreatitis at 5 years after the surgery were 32.5 and
      26.1 %, respectively (p = 0.70). CONCLUSIONS: Careful long-term follow-up is
      needed for patients undergoing pancreatectomy for type 1 AIP because remnant
      pancreatic function can deteriorate as severely as that of patients who undergo
      pancreatectomy for conventional chronic pancreatitis. In the present series,
      however, there were few definite manifestations indicating relapse or the
      persistent existence of AIP.

PMID- 23010700
TI  - Efficacy of 10% sucralfate ointment in the reduction of acute postoperative pain
      after open hemorrhoidectomy: a prospective, double-blind, randomized, placebo
      controlled trial.
AB  - BACKGROUND: The aim of the present study was to evaluate the efficacy of 10 %
      sucralfate ointment in the reduction of acute postoperative pain after open
      hemorrhoidectomy. METHODS: A total of 48 patients (24 men and 24 women) between
      20 and 70 years of age who underwent open hemorrhoidectomy were included in this
      prospective, double-blind, randomized, controlled trial and were randomly divided
      into two groups (24 in each group), receiving either sucralfate ointment or
      placebo immediately after surgery and then every 12 h for 14 days. The primary
      outcome measure was pain intensity measured by a visual analogue scale at
      different time points after hemorrhoidectomy. RESULTS: The sucralfate group had
      significantly less pain than the placebo group at 24th h and the 48th h after
      hemorrhoidectomy (4 +/- 1.14 vs 5.08 +/- 0.97; P = 0.001 and 3 +/- 0.72 vs 4.41
      +/- 0.8; P < 0.001, respectively), and they consumed lower amounts of analgesics
      at the same time intervals (12.50 +/- 16.48 vs 21.87 +/- 15.30 mg of pethidine; P
      = 0.047 and 152 +/- 23 vs 172 +/- 29 mg of diclofenac; P = 0.009, respectively).
      The same trend continued until the end of the trial. CONCLUSIONS: Sucralfate
      ointment reduced the acute postoperative pain after hemorrhoidectomy.

PMID- 23010701
TI  - Withdrawing artificial nutrition and patients' interests.
AB  - I argue that the arguments brought by Counsel for M to the English Court of
      Protection are morally problematic in prioritising subjective interests that are
      the result of 'consistent autonomous thought' over subjective interests that are
      the result of a more limited cognitive perspective. 

PMID- 23010702
TI  - Underrecognition of pathologist contributions to articles published in a major
      multidisciplinary medical journal.
AB  - The Canadian Medical Association Journal (CMAJ) is a high-impact
      multidisciplinary medical journal. We have observed instances in which a
      pathology diagnosis, documented with gross or microscopic images, forms an
      integral part of a CMAJ article, but a pathologist is neither an author nor
      acknowledged as a contributor. To examine the hypothesis that pathologist
      contributions are underrecognized and/or underdocumented, we reviewed all CMAJ
      articles over a 6-year period (September 2003-2009), and correlated the use of
      pathology images with pathologist authorship or contribution. For each article
      containing pathology images, department affiliations of authors were determined,
      and acknowledgments were assessed. Although only 1.7% of articles contained
      pathology images, 47% (26/55) of these articles did not include a pathologist as
      either an author or a contributor. We conclude that important intellectual
      contributions of pathologists are underrecognized and suggest that the scientific
      credibility of pathology data is in doubt when pathologists do not take on full
      responsibility of authorship or are not acknowledged as contributors.

PMID- 23010703
TI  - Pathology consultation on transfusion-related acute lung injury (TRALI).
AB  - Transfusion-related acute lung injury (TRALI) is a serious condition
      characterized by respiratory distress, hypoxia, and bilateral pulmonary
      infiltrates, which occur within 6 hours of transfusion. Several theories have
      been proposed to explain the underlying pathologic mechanisms of TRALI. Immune
      mediated TRALI accounts for over 80% of reported cases and is mediated by donor
      antibodies to HLAs and/or human neutrophil antigens (HNA). Immune-mediated TRALI
      is most commonly associated with donor plasma transfusion or other blood products
      from multiparous women, which has led many countries to reduce or exclude women
      from donating high-volume plasma products. This policy change has resulted in a
      decrease in the incidence of TRALI and highlighted the importance of nonimmune
      mediated TRALI, which is thought to be caused by bioreactive lipids and other
      biologic response modifiers that accumulate during storage of blood products.
      When TRALI is suspected, clinical consultation with a transfusion medicine
      specialist helps differentiate it from other transfusion reactions with similar
      characteristics.

PMID- 23010704
TI  - Pathologic findings associated with invasive EEG monitoring for medically
      intractable epilepsy.
AB  - Invasive electroencephalography (EEG) monitoring is often needed for presurgical
      evaluation in patients with medically intractable epilepsy (MIE). This study
      retrospectively reviews the pathologic changes associated with EEG monitoring.
      Two hundred twenty-six patients who underwent invasive monitoring (53.5% males;
      mean age, 29.8 years) and 55 controls without EEG monitoring (52.7% males; mean
      age, 25.6 years) were evaluated. Median length of invasive EEG monitoring was 7.0
      days. Compared with controls, patients who were monitored had more pathologic
      changes related to invasive EEG monitoring (n = 171 [75.7%] vs n = 12 [21.8%]; P
      < .0001) including meningeal or parenchymal chronic inflammation (n = 128 [56.4%]
      vs n = 11 [20.4%]; P < .0001) and acute contusion and/or acute/subacute infarct
      (n = 110 [48.5%] vs n = 0; P < .0001). Histologic evidence of pathologic changes
      typically associated with invasive monitoring and/or craniotomy occurred in 76%
      of our patients with invasive monitoring compared with 19% in patients without
      prior invasive EEG evaluation. The most common pathologic changes related to
      invasive monitoring were chronic inflammation and contusion/infarct.

PMID- 23010705
TI  - Decreased androgen receptor expression is associated with distant metastases in
      patients with androgen receptor-expressing triple-negative breast carcinoma.
AB  - To characterize prognostic values of androgen receptor (AR) in triple-negative
      (TN) breast cancers, we investigated AR expression status and levels, explored an
      association of AR expression with metastatic disease, and correlated AR
      expression with Ki-67 in TN invasive breast carcinomas. AR expression was
      analyzed with immunohistochemistry in 121 cases of TN tumors. Thirty-nine cases
      had distant metastatic disease and 82 had locoregional disease only. AR was
      positive in 38 (31.4%) of the 121 cases. Our results indicate that among the AR
      positive TN tumors, distant metastases are significantly associated with lower
      expression of AR compared with cases with only locoregional disease, and that AR
      expression negatively correlates with Ki-67 expression. These findings suggest
      that decreased intratumoral AR expression may be predictive of distant metastatic
      disease and AR expression levels may have potential prognostic value in AR
      expressing TN tumors.

PMID- 23010706
TI  - Follow-up outcomes in a large cohort of patients with human papillomavirus
      negative ASC-H cervical screening test results.
AB  - Limited follow-up data are available on patients with cervical cytology results
      of atypical squamous cells, cannot exclude a high-grade intraepithelial lesion
      (ASC-H), who test negative for high-risk human papillomavirus (hrHPV). Between
      June 2005 and December 2010, 885 patients were identified with ThinPrep results
      of Hybrid Capture 2 (HC2) hrHPV-negative cervical ASC-H liquid-based cytology and
      follow-up histopathology or cytology results extending to September 2011. Of the
      885 patients with available follow-up results, 549 (62.0%) had at least 1
      histopathologic result during the entire follow-up period, whereas 336 (38.0%)
      had only cytologic follow-up documented. In an average follow-up period of 29
      months, 14 (1.6%) of 885 patients with HPV-negative ASC-H results showed evidence
      of high-grade cervical intraepithelial neoplasia (CIN2/3). No cases of invasive
      cervical cancer were diagnosed. Four of 14 patients with HPV-negative ASC-H
      results with follow-up diagnoses of CIN2/3 had a history of earlier CIN2/3
      diagnoses before HPV-negative ASC-H results. Follow-up of patients with HPV
      negative ASC-H results using methods specified in this study yielded low rates of
      detectible CIN2/3 and no diagnoses of cervical cancer. Triage of study patients
      with HPV-negative ASC-H results to routine HPV and cytology cotesting at 1 year
      was a safe follow-up option.

PMID- 23010707
TI  - Assessing endometrial hyperplasia and carcinoma treated with progestin therapy.
AB  - The effects of increased amounts of progesterone on the endometrium, including
      such features as eosinophilic cytoplasmic metaplasia, glandular atrophy, and
      decidualized stroma, are well-known among surgical pathologists. These changes
      are typically seen as secondary effects of pregnancy or exogenous hormone therapy
      for birth control purposes or abnormal bleeding. Treatment with progesterone has
      become a viable alternative to hysterectomy in some patients with complex
      atypical hyperplasia (CAH) and well-differentiated endometrial carcinoma (WDC),
      especially those who are poor surgical candidates or those wishing to preserve
      fertility. To date, only 1 study has specifically examined the effects of
      progestin therapy on patients with a previous diagnosis of CAH or WDC. That study
      proposed a classification scheme for the assessment of treated CAH and WDC. The
      authors concluded that after 6 months of treatment, endometrial biopsy findings
      of persistent cytologic atypia and architectural abnormalities were associated
      with treatment failure. This current study aims to assess the previously proposed
      criteria in a cohort of 30 patients (18 with a diagnosis of CAH and 12 with a
      diagnosis of WDC), and determine the usefulness of these criteria in clinical
      practice. Our study confirms that cytologic atypia after 6 months of therapy is
      strongly associated with treatment failure, and should be an indication to pursue
      definitive surgical treatment in these patients.

PMID- 23010708
TI  - Notch3 overexpression as potential therapeutic target in advanced stage
      chemoresistant ovarian cancer.
AB  - This study examined the clinical significance of Notch3 expression and assessed
      its usefulness as a potential therapeutic target in chemoresistant ovarian
      cancer. Notch3 expression was assessed with immunohistochemical examination, and
      clinical variables were collected with a retrospective chart review. Notch3 siRNA
      or gamma-secretase inhibitor was used to assess Notch3 function in ovarian cancer
      cell lines. Notch3 overexpression correlated with shorter progression
      free/overall survival in patients with advanced stage (stage III, IV) ovarian
      carcinoma treated with platinum and taxane. Three of 5 patients showed increased
      Notch3 immunostaining in recurrent tumors compared with corresponding primary
      tumors. Notch3 overexpression was observed in both the cisplatin-resistant KFr13
      and cisplatin/paclitaxel-resistant KFr13Tx cells. Inactivation of Notch3 by gamma
      secretase inhibitor or siRNA decreased cell proliferation and induced apoptosis
      in the KFr13 and KFr13Tx cells. Our findings suggest that Notch3 expression may
      be related to chemoresistance and that the Notch3 pathway may represent a novel
      therapeutic target for advanced stage chemoresistant ovarian cancer.

PMID- 23010709
TI  - Bleeding risks and response to therapy in patients with INR higher than 9.
AB  - An international normalized ratio (INR) higher than 9 is associated with a high
      risk of bleeding, yet most studies have focused on outpatients with lower INR. We
      retrospectively analyzed diagnosis, bleeding, treatment, and mortality in 162
      patients with INR higher than 9, including inpatients and outpatients with and
      without warfarin treatment. Patients without anticoagulant treatment with INR
      higher than 9 had a poor prognosis, 67% experienced bleeding and 74% died. Among
      outpatients receiving warfarin with INR higher than 9, 11% had bleeding, but none
      died. Among inpatients receiving warfarin, 35% had bleeding and 17% died. Factors
      associated with bleeding were older age, renal failure, and alcohol use.
      Withholding warfarin or giving vitamin K treatment was ineffective at reducing
      the INR within 24 hours, whereas plasma infusion immediately dropped the INR to
      2.4 +/- 0.9. Because of underlying disease, comorbidities, and medications,
      hospitalized patients with INR higher than 9 may not respond quickly to
      withholding warfarin or vitamin K treatment, and plasma infusion may be needed to
      reduce INR and the risk of bleeding within 24 hours.

PMID- 23010710
TI  - Measuring direct thrombin inhibitors with routine and dedicated coagulation
      assays: which assay is helpful?
AB  - The use of direct thrombin inhibitors (DTIs) for prophylactic or therapeutic
      anticoagulation is increasing because of the predictable bioavailability and
      short half-life of these DTIs. However, in certain situations, indication of the
      concentration is warranted. We investigated the effects of 3 DTIs (lepirudin,
      argatroban, and bivalirudin) in 6 pooled plasma specimens on routine coagulation
      assays (activated partial thromboplastin time [aPTT], prothrombin time [PT], and
      thrombin time [TT]) and dedicated DTI assays (Hemoclot, HemosIL, the ecarin
      clotting time, and a chromogenic ecarin clotting time) on 2 coagulation
      analyzers. We found routine tests to be nondiscriminative between concentrations
      of different DTIs in the aPTT. Moreover, for PT and TT, the responses for
      different DTIs differed. This was similar for ecarin clotting assays. The
      Hemoclot and HemosIL assays showed identical linear increases for all 3 DTIs. We
      conclude that dedicated calibrated assays based on a diluted TT (Hemoclot and
      HemosIL) appear to be the most suitable for monitoring purposes.

PMID- 23010711
TI  - Informed consent for blood transfusion: what do medicine residents tell? What do
      patients understand?
AB  - Blood transfusion is a common intervention in the hospital setting, and its
      benefits may not be clear but it has associated risks. Despite this, transfusion
      consent may not be obtained satisfactorily. We assessed transfusion consent
      effectiveness by comparing information given by residents with information
      understood by patients who receive transfusions. Medicine department residents
      who obtained consent were surveyed via telephone in conjunction with bedside
      surveys of adult inpatients who received transfusions. A total of 43 patient and
      34 resident surveys were completed. Deficiencies in the transfusion consent
      process were noted. Discussed transfusion benefits (such as wound healing) were
      not always true benefits whereas some important risks (such as transfusion
      related acute lung injury) were infrequently conferred. Risks were more often
      reported as "not discussed" than benefits. Only a few participants were aware of
      the hospital's Transfusion Health Guide, which provides information on
      transfusion benefits, risks, and alternatives.

PMID- 23010712
TI  - Early posttransplant lymphoproliferative disease: clinicopathologic features and
      correlation with mTOR signaling pathway activation.
AB  - Early posttransplant lymphoproliferative disorders (EPTLDs) represent the first
      changes in posttransplant lymphoproliferative disorders (PTLDs) morphologic
      spectrum. EPTLD data are available mostly from case reports and series that
      include other types of PTLD. Fifteen EPTLDs were reviewed retrospectively.
      Clinical data, histopathology, clonality, and Epstein- Barr virus (EBV) status
      were correlated with staining intensity to an antibody for phosphorylated S6
      (pS6) ribosomal protein, a downstream effector of mammalian target of rapamycin
      (mTOR). Median time from transplantation to EPTLD was 50 months (range, 7-135
      mo). EPTLDs involved tonsil and/or adenoids (n = 11) and lymph nodes (n = 4), all
      of which were nonclonal and EBV-encoded RNA-positive. Most (n = 11) were
      plasmacytic hyperplasia and florid follicular hyperplasia (n = 4). All regressed
      with reduced immunosuppression, and had increased pS6 staining compared with
      normal tonsil (P = .002, F test). EPTLDs developed later than previously
      reported, involved mostly tonsils/adenoids, were EBV-encoded RNA (EBER) positive,
      showed increased pS6, and had excellent clinical outcome with reduction of
      immunosuppression.

PMID- 23010713
TI  - Array-based karyotyping in plasma cell neoplasia after plasma cell enrichment
      increases detection of genomic aberrations.
AB  - The discovery of genomic abnormalities present in monoclonal plasma cells has
      diagnostic, prognostic, and disease-monitoring implications in plasma cell
      neoplasms (PCNs). However, technical and disease-related limitations hamper the
      detection of these abnormalities using cytogenetic analysis or fluorescence in
      situ hybridization (FISH). In this study, 28 bone marrow specimens with known
      PCNs were examined for the presence of genomic abnormalities using microarray
      analysis after plasma cell enrichment. Cytogenetic analysis was performed on 15
      of 28 samples, revealing disease-related genomic aberrations in only 3 (20%) of
      15 cases. FISH analysis was performed on enriched plasma cells and detected
      aberrations in 84.6% of specimens while array comparative genomic hybridization
      (aCGH) detected abnormalities in 89.3% of cases. Furthermore, aCGH revealed
      additional abnormalities in 24 cases compared with FISH alone. We conclude that
      aCGH after plasma cell enrichment, in combination with FISH, is a valuable
      approach for routine clinical use in achieving a more complete genetic
      characterization of patients with PCN.

PMID- 23010714
TI  - Fluorescence microscopy is superior to polarized microscopy for detecting amyloid
      deposits in Congo red-stained trephine bone marrow biopsy specimens.
AB  - The classic gold standard for detecting amyloid deposits is Congo red-stained
      bright field and polarized microscopy (CRPM). A prior study showed that Congo red
      fluorescence (CRF) microscopy had increased sensitivity compared with traditional
      CRPM when analyzing fat pad specimens. The purpose of the current study was to
      determine the sensitivity of CRF for evaluating Congo red-stained bone marrow
      biopsy specimens, and to compare these results with those of CRPM. We compared
      the CRPM and the CRF analyses of 33 trephine bone marrow biopsy specimens with
      clinical or morphologic suspicion of amyloid deposits. These results were
      verified against immunohistochemical staining with anti-amyloid P antibody. CRF
      achieved 100% sensitivity, and CRPM achieved 75% sensitivity. Both groups showed
      100% specificity compared with amyloid P immunohistochemical staining. The
      results show that CRF is a sensitive method to analyze trephine bone marrow
      biopsy specimens for amyloid deposits.

PMID- 23010715
TI  - Application of linear discriminant analysis in performance evaluation of
      extractable nuclear antigen immunoassay systems in the screening and diagnosis of
      systemic autoimmune rheumatic diseases.
AB  - This study applied a linear discriminant analysis model to evaluate the
      performance of 2 types of commercially available extractable nuclear antigen
      (ENA) immunoassays for the screening and diagnosis of systemic autoimmune
      rheumatic diseases (SARDs) in a large tertiary hospital reference laboratory: (1)
      an enzyme-linked immunosorbent assay (ELISA) and (2) a multiplex bead-based
      immunoassay (MPBI). The results of the study showed both ENA immunoassays had
      comparable sensitivity for the detection of SARDs compared with the antinuclear
      antigen immunofluorescence (ANA-IF) method (ANA-IF: 85.6%, ENA-ELISA: 91.5%, ENA
      MPBI: 83.1%, pairwise comparisons with ANA-IF: P > .05). However, both ENA
      immunoassays offered improved specificity compared with the ANA-IF (ANA-IF:
      24.2%; ENA-ELISA: 39.8%; ENA-MPBI: 53.1%; pairwise comparison with ANA-IF: P <
      .001). The use of a more specific screening immunoassay with comparable
      sensitivity to ANA-IF is important in a tertiary hospital with high prevalence of
      non-SARD immune diseases. Diagnostic performance of the ENA/dsDNA components by
      the MPBI and ELISA methods did not differ significantly (area under the curve
      [AUC], 81.0% vs 83.0%, respectively, P > .05), but the key ENA/dsDNA variables
      contributing to the discriminating power of the assays for the diagnosis of
      specific SARDs were reagent/method dependent.

PMID- 23010716
TI  - Identification of M protein from filter paper using serum protein and
      immunofixation electrophoresis.
AB  - Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) are
      standard methods for detection and monitoring of monoclonal (M) proteins.
      However, these tests are rarely available in the remote areas, especially in
      developing countries. Transportation of fresh serum (FS) samples is also usually
      inconvenient. This study investigated M-protein identification using serum blot
      on filter paper (FP). SPE and IFE were performed on FS and FP specimens using the
      Sebia Hydrasys automated electrophoresis system. Statistical analyses were
      conducted to assess sample stability and agreement of FS vs FP. The FP method
      showed good agreement with the FS method. The r values for correlation of albumin
      levels-alpha(1), alpha(2), beta, and gamma (%)-between FP and FS samples in SPE
      were all more than 0.95 (P < .01). IFE displayed no significant difference
      between those 2 methods in the identification of M protein. The FP method
      demonstrated an accurate and reproducible alternative to FS for identification of
      M protein using SPE and IFE.

PMID- 23010717
TI  - Laboratory persistence and clinical progression of small monoclonal
      abnormalities.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) that presents with no
      quantifiable M spike on immunofixation electrophoresis (IFE) can be termed IFE
      MGUS. We retrospectively identified patients with IFE MGUS who were monitored
      with at least 1 subsequent assessment that included an IFE, and evaluated the
      persistence of the monoclonal protein and the progression of disease. Although
      the monoclonal proteins persisted in the majority of patients, 16% did not
      experience this persistence, and had no documented immunomodulatory therapy.
      After a median follow-up of 3.9 years, the disease clinically progressed in 14
      patients (3.2%). Eight of these 14 patients with clinical progression had an
      immunoglobulin (Ig) A IFE M protein and 6 had an IgG M protein. This study
      demonstrates that in some patients with IFE MGUS, the M proteins are transient
      and that IgA IFE MGUS is more likely to persist and progress to myeloma.

PMID- 23010718
TI  - Factors associated with alkali production from arginine in dental biofilms.
AB  - Alkali production by oral bacteria in the oral cavity has been linked to
      protection against dental caries. The current study assessed various parameters
      associated with ammonium produced during arginine catabolism in dental biofilms.
      Polymicrobial biofilms were formed with saliva as the inoculum. The NH(3) level
      and the pH of the spent medium were used to monitor and quantitate the bacterial
      reactions. The presence of sucrose, a low buffer capacity, and a low pH (<= pH
      4.5) were found to hamper alkali production from arginine. The rate of alkali
      production exhibited an optimum around pH 5.5. Biofilms were found to produce
      NH(3) also from polypeptides and proteins in the medium. The biofilm age affected
      these processes. The experimental model proved valuable for the assessment of the
      collective bacterial reactions determining the overall pH outcome. This
      experimental approach could bridge the gap in our knowledge between pH-rise
      phenomena and caries susceptibility from clinical observations and studies
      performed on alkali-producing bacteria in well- controlled, though simplified, in
      vitro models. Analysis of our data supports the hypothesis that the initiation
      and progression of dental caries may be influenced by the relative rates of acid
      and base formation, which critically depend on the aforementioned parameters.

PMID- 23010719
TI  - SHP is involved in BMP2-induced odontoblast differentiation.
AB  - Small Heterodimer Partner (SHP) interacts with diverse transcription factors such
      as Runx2 and regulates many cellular events including differentiation,
      proliferation, and energy metabolism. SHP is reported to be a positive regulator
      of BMP2-induced bone formation. This study aimed to clarify the role of SHP in
      odontoblast differentiation and matrix mineralization. Rat tooth germs were
      isolated, and gene expression was determined by RT-PCR and real-time PCR.
      Localization of SHP protein expression was identified by immunofluorescent
      analysis. Primary human dental pulp cells (HDPCs) were cultured with BMP2 and/or
      Ad-siSHP. Matrix mineralization was evaluated by Alizarin red staining. Transient
      transfection experiment was performed with the SHP or Dlx5 expressional plasmids
      and the DSPP gene. In tooth germs from post-natal days 3 to 9, BMP-2 and SHP
      expression increased with DSPP and DMP1 mRNA expression. In an immunostaining
      study, SHP was expressed in odontoblasts and surrounding osteoblasts. When HDPCs
      were cultured with BMP2 in mineralization-inducing medium, SHP expression also
      increased with an increase in DSPP expression. Down-regulation of SHP by Ad-siSHP
      inhibited matrix mineralization. In transient transfection experiments,
      overexpression of SHP was shown to enhance DSPP promoter activity through
      interactions between SHP and Dlx5. These results suggest that SHP may mediate
      BMP2 signaling to promote mineralization of the dentin matrix.

PMID- 23010720
TI  - Biological nitrogen and phosphorus removal in membrane bioreactors: model
      development and parameter estimation.
AB  - Membrane bioreactors (MBR) are being increasingly used for wastewater treatment.
      Mathematical modeling of MBR systems plays a key role in order to better explain
      their characteristics. Several MBR models have been presented in the literature
      focusing on different aspects: biological models, models which include soluble
      microbial products (SMP), physical models able to describe the membrane fouling
      and integrated models which couple the SMP models with the physical models.
      However, only a few integrated models have been developed which take into account
      the relationships between membrane fouling and biological processes. With respect
      to biological phosphorus removal in MBR systems, due to the complexity of the
      process, practical use of the models is still limited. There is a vast knowledge
      (and consequently vast amount of data) on nutrient removal for conventional
      activated sludge systems but only limited information on phosphorus removal for
      MBRs. Calibration of these complex integrated models still remains the main
      bottleneck to their employment. The paper presents an integrated mathematical
      model able to simultaneously describe biological phosphorus removal, SMP
      formation/degradation and physical processes which also include the removal of
      organic matter. The model has been calibrated with data collected in a UCT-MBR
      pilot plant, located at the Palermo wastewater treatment plant, applying a
      modified version of a recently developed calibration protocol. The calibrated
      model provides acceptable correspondence with experimental data and can be
      considered a useful tool for MBR design and operation.

PMID- 23010721
TI  - Synthesis of nylon 4 from gamma-aminobutyrate (GABA) produced by recombinant
      Escherichia coli.
AB  - In this study, we developed recombinant Escherichia coli strains expressing
      Lactococcus lactis subsp. lactis Il1403 glutamate decarboxylase (GadB) for the
      production of GABA from glutamate monosodium salt (MSG). Syntheses of GABA from
      MSG were examined by employing recombinant E. coli XL1-Blue as a whole cell
      biocatalyst in buffer solution. By increasing the concentration of E. coli XL1
      Blue expressing GadB from the OD600 of 2-10, the concentration and conversion
      yield of GABA produced from 10 g/L of MSG could be increased from 4.3 to 4.8 g/L
      and from 70 to 78 %, respectively. Furthermore, E. coli XL1-Blue expressing GadB
      highly concentrated to the OD600 of 100 produced 76.2 g/L of GABA from 200 g/L of
      MSG with 62.4 % of GABA yield. Finally, nylon 4 could be synthesized by the bulk
      polymerization using 2-pyrrolidone that was prepared from microbially synthesized
      GABA by the reaction with Al2O3 as catalyst in toluene with the yield of 96 %.

PMID- 23010722
TI  - Reaction engineering analysis of cellulase production with Trichoderma reesei RUT
      C30 with intermittent substrate supply.
AB  - The effects of varying initial concentrations of microcrystalline cellulose on
      cellulase production with Trichoderma reesei RUT-C30 as well as the effects of
      varying lactose and ammonium sulfate concentrations in the feed medium were
      studied simultaneously in parallel-operated shake flasks and, alternatively, in
      parallel-operated stirred-tank bioreactors on a 10-mL scale. Fifteen experiments
      were performed as triplicates in shake flasks as well as in stirred-tank
      bioreactors in parallel to identify the parameters of second-order polynomials
      for the estimation of the final filter paper activity of T. reesei RUT-C30 after
      a process time of 96 h. Even though parameter estimation was not possible based
      on the results of the shake flasks due to final enzyme activities at or below the
      detection limit (with the exception of one shake flask), the identification of
      the second-order polynomial was successful with the results of the parallel
      operated stirred-tank bioreactors on a 10-mL scale. Reaction conditions with 53.3
      g L-1 microcrystalline cellulose in the initial medium, no lactose feeding and
      3.3 g L-1 day-1 intermittent ammonium sulfate addition were estimated to be
      optimal. The final experimental validation of the optimum substrate supply on a L
      scale resulted in the production of 4.88 filter paper units (FPU) mL-1 with T.
      reesei RUT-C30 after 96 h. This is an improvement by a factor of 3.6 compared to
      the reference batch process (1.35 FPU mL-1).

PMID- 23010723
TI  - The effect of hydrodynamic stress on the growth of Xanthomonas campestris
      cultures in a stirred and sparged tank bioreactor.
AB  - The specific growth and the xanthan production rates by the bacterium Xanthomonas
      campestris under different shear levels in shake flasks and in a stirred and
      sparged tank bioreactor have been studied. The shake flask has been used as a
      reference for studying the shear effects. An effectiveness factor expressed by
      the ratio of the observed growth rate and the growth rate without oxygen
      limitation or cell damage was calculated in both modes of cultures. It was
      observed that the effectiveness factor was strongly dependent on the operational
      conditions. A strong oxygen transfer limitation at low stirring rates, indicated
      by a 54 % decrease in the effectiveness factor was observed. In contrast, at
      higher stirrer speed, cell damage was caused by hydrodynamic stress in the
      turbulent bulk of the broth, yielding again a decrease in the effectiveness
      factor values for stirrer speeds higher than 500 rpm. Cell morphological changes
      were also observed depending on the agitation conditions, differences in
      morphology being evident at high shear stress.

PMID- 23010724
TI  - Characterization of stirrers for screening studies of enzymatic biomass
      hydrolyses on a milliliter scale.
AB  - The evaluation of mixing quality is an important factor for improving the
      geometry of stirred-tank reactors and impellers used in bioprocess engineering
      applications, such as the enzymatic hydrolysis of plant materials. Homogeneity
      depends on different factors, including the stirrer type and the reactor type
      (e.g., ratio of diameter/height, ratio of impeller tip diameter/reactor diameter)
      with or without baffles. This study compares two impellers for enzymatic
      hydrolysis of suspensions of biomass particles on a milliliter scale. Both
      impellers were derived from industrially relevant geometries, such as blade and
      grid stirrers, although the geometry of the second stirrer was slightly modified
      to an asymmetric shape. The stirrers were investigated with different stirrer
      reactor configurations. This was done experimentally and with the aid of
      computational fluid dynamics. The flow field, mixing numbers, power
      characteristics and initial conversion rates of sugars were considered to compare
      the two stirrers. The simulated mixing numbers and power characteristics in
      baffled and unbaffled milliliter-scale reactors were found to be in good
      agreement with the measured mixing times and power consumption. The mixing
      numbers required to reach homogeneity were much higher for the symmetric impeller
      and remained at least twice as high as the mixing numbers required when using the
      asymmetric impeller. The highest initial sugar releases from milled corn stover
      suspensions were achieved with the asymmetric impeller shape. Regardless of the
      differences in the flow fields or mixing times, diverging enzymatic sugar
      releases could be confirmed for Newtonian media only.

PMID- 23010725
TI  - Pilot-scale production of fuel ethanol from concentrated food waste hydrolysates
      using Saccharomyces cerevisiae H058.
AB  - The aim of this study was to develop a bioprocess to produce ethanol from food
      waste at laboratory, semipilot and pilot scales. Laboratory tests demonstrated
      that ethanol fermentation with reducing sugar concentration of 200 g/L, inoculum
      size of 2 % (Initial cell number was 2 * 106 CFU/mL) and addition of YEP (3 g/L
      of yeast extract and 5 g/L of peptone) was the best choice. The maximum ethanol
      concentration in laboratory scale (93.86 +/- 1.15 g/L) was in satisfactory with
      semipilot scale (93.79 +/- 1.11 g/L), but lower than that (96.46 +/- 1.12 g/L) of
      pilot-scale. Similar ethanol yield and volumetric ethanol productivity of 0.47 +/
      0.02 g/g, 1.56 +/- 0.03 g/L/h and 0.47 +/- 0.03 g/g, 1.56 +/- 0.03 g/L/h after
      60 h of fermentation in laboratory and semipilot fermentors, respectively,
      however, both were lower than that (0.48 +/- 0.02 g/g, 1.79 +/- 0.03 g/L/h) of
      pilot reactor. In addition, simple models were developed to predict the
      fermentation kinetics during the scale-up process and they were successfully
      applied to simulate experimental results.

PMID- 23010726
TI  - Adsorption of alcohol from water by poly(ionic liquid)s.
AB  - Bioethanol is used widely as a solvent and is considered a potential liquid fuel.
      Ethanol can be produced from biomass by fermentation, which results in low
      concentrations of alcohol in water. Conventional distillation is normally used to
      separate ethanol from water, but it required high energy consumption. Therefore,
      alternative approaches to this separation are being pursued. This study examined
      the potential use of poly(ionic liquid)s (PILs) for the extraction and separation
      of alcohols from the aqueous phase. Hydrophobic PILs were developed and evaluated
      by the adsorption of ethanol from ethanol/water solutions. All the necessary
      parameters, such as cations and anions of the ionic liquid, morphology of the
      polymer and processing conditions, were evaluated.

PMID- 23010727
TI  - The glucose metabolic frame of conditions induce the overproduction of a co
      culture pigment: induction mechanism of the pigment and development of a specific
      eutrophic-oligotrophic transition cultivation system.
AB  - Induction mechanism of a potential red pigment (RPc) was investigated in the
      present paper. A typical competition relationship exists between Penicillium sp.
      HSD07B and Candida tropicalis during co-culture, and C. tropicalis converts
      glucose into glycerol, organic acids and other substances, resulting in a
      stricter glucose limitation and the secretion of RPc. Moreover, a novel eutrophic
      oligotrophic transition cultivation system (E-OTCS) was developed to produce red
      pigment during monoculture of Penicillium sp. HSD07B. However, the monoculture
      pigment (RPm) is different from RPc in components, and RP3 and RP4 only occur in
      RPm when glycerol is supplied. In addition, the additions of glycerol and organic
      acids to glucose exhaustion medium can significantly improve the pigment yield.
      These facts not only prove the feasibility of producing RPm using E-OTCS, but
      also reveal that, besides glucose exhaustion, the accumulation of metabolites of
      glucose including glycerol and organic acids is also an important factor
      influencing the production of RPc.

PMID- 23010728
TI  - First steps towards conformationally selective artificial lectins: the chair-boat
      discrimination by molecularly imprinted polymers.
AB  - A series of molecularly imprinted polymers (MIPs) were prepared in the presence
      of a synthetic galactoside locked in a (1,4)B boat conformation. This study
      demonstrates that, depending on the polymerisation technique, an organic material
      can selectively bind a carbohydrate in a biologically relevant boat conformation.

PMID- 23010729
TI  - Vaginal reconstruction following radical surgery for colorectal malignancies: a
      systematic review of the literature.
AB  - INTRODUCTION: Vaginectomy is frequently indicated to ensure an adequate resection
      in rectal cancer. This paper reviews the success, complications, and functional
      results after various methods of vaginal reconstruction following resection for
      rectal tumors. METHODS: A systematic review of the literature was performed by
      using the MEDLINE database, Embase, and the Cochrane library (1990-2010).
      RESULTS: Eighteen papers were available to review. Fifty percent of all women who
      received a neovagina following vaginectomy returned to sexual activity
      postoperatively. The rectus abdominis myocutaneous (RAM) flap remains the most
      common method of vaginal reconstruction after surgery for colorectal cancer.
      Advantages include low operative morbidity, a wide arc of rotation, and ease of
      harvest. Alternatives to flap reconstruction of the vagina have limited
      indications because of higher morbidity rates. CONCLUSIONS: Preferred techniques
      for vaginal reconstruction following vaginectomy with colorectal cancer resection
      include RAM flaps for partial posterior vaginal defects and bilateral Gracilis
      myocutaneous flaps for complete vaginal excisions.

PMID- 23010730
TI  - A comparison of clinical and pathologic assessments for the prediction of occult
      nipple involvement in nipple-sparing mastectomies.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) for both risk reduction and cancer is
      increasing. In the cancer setting, most studies suggest the use of both clinical
      and intraoperative biopsy criteria in patient selection. This study examines the
      use of both biopsy and clinical criteria in women undergoing total nipple
      removing mastectomy. METHODS: The study consisted of 58 patients undergoing total
      mastectomy without nipple sparing. Biopsies of the subareola tissue (SA),
      proximal nipple (NC) contents and radial sections of the residual nipple (NR)
      were examined microscopically. Tumor size and distance from the nipple were also
      noted. RESULTS: Using clinical criteria alone, the false negative rate was 53.8%
      and a false positive rate of 44.4%. When adding subareola and nipple core
      biopsies to clinical criteria the false negative rate fell to 7.7% but the false
      positive rate remained at 44.4%. When using only SA and NC biopsies to predict
      occult nipple involvement, the false negative rate was 11.8%. In 4 cases the NC
      was positive while the SA was negative for cancer and in 6 cases the SA was
      positive and NC negative. In 2 cases both the NC and SA biopsies were negative
      while the NR was positive. CONCLUSIONS: This study supports a more limited role
      in the use of clinical criteria for evaluating patients for NSM. This maximizes
      the number of patients who are candidates for NSM with minimal risk of nipple
      involvement. It was also noted that intraoperative biopsies are not totally
      reliable in predicting occult nipple involvement.

PMID- 23010731
TI  - 1 or 2 cm margins of excision for T2 melanomas: do they impact recurrence or
      survival?
AB  - BACKGROUND: NCCN guidelines recommend 1 or 2 cm margins for melanomas 1-2 mm (T2
      melanomas) in depth; however, no head-to-head comparison has been performed. We
      hypothesized 1- or 2-cm margins would have similar local recurrence (LR) and
      overall survival (OS). METHODS: An institutional database was queried for
      patients with 1.0-2.0 mm melanomas treated from July 1995 to January 2011. All
      had wide excision and sentinel lymph node biopsy. Patients without documented
      surgical margins or follow-up were excluded. Clinicopathologic and recurrence
      data were reviewed. Univariate and multivariate analyses were performed. RESULTS:
      Of 2,118 patients, 1,225 met study criteria. Of these, 576 had complete data: 224
      (38.9%) had 1 cm margins and 352 (61.1%), 2 cm margins. Median follow-up was 38
      months. Mean age was 52.6 years (range 11.3-86.7). Mean thickness was 1.27 and
      1.48 mm (1 and 2 cm, respectively, p<0.001) with ulceration more common in the 2
      cm group (12.3 and 21.3%, respectively; p=0.009). LR was 3.6 and 0.9% in the 1 cm
      versus 2 cm group, respectively (p=0.044). OS was 29.1 months with 1 cm and 43.7
      months in the 2 cm group. On multivariate analysis, only head and neck location
      and nodal status were associated with overall survival. CONCLUSIONS: In this
      series, 1 cm margins were associated with a small increase in LR that did not
      impact OS. This is concordant with the NCCN recommendations; however, a
      prospective, randomized trial would be optimal.

PMID- 23010732
TI  - Effect of prophylactic central compartment neck dissection on serum thyroglobulin
      and recommendations for adjuvant radioactive iodine in patients with
      differentiated thyroid cancer.
AB  - BACKGROUND: Controversy exists in the management of patients with differentiated
      thyroid cancer (DTC). The purpose of this study was to examine the effect of
      prophylactic central compartment neck dissection (CCND) on serum thyroglobulin
      (Tg) levels and recommendations for adjuvant radioactive iodine (RAI). METHODS:
      The records of 103 patients who underwent completion/total thyroidectomy for DTC
      between January 2009 and November 2010 were reviewed. Prophylactic CCND was
      defined as removal of central compartment lymph nodes with no preoperative or
      intraoperative evidence of lymphadenopathy. Institutional protocol included a
      diagnostic whole-body scan before RAI; patients with a negative scan and Tg < 2.0
      did not receive adjuvant RAI. RESULTS: Among the 103 patients, therapeutic CCND
      was performed in 17 (17 %) and prophylactic CCND in 49 (48 %). Of the 49
      patients, 20 (41 %) had positive cervical lymph nodes. Positive lymph nodes
      changed American Joint Committee on Cancer tumor, node, metastasis staging in 17
      patients and recommendations for RAI in 14. At a median follow-up of 21 months,
      there was no difference in Tg level based on the application of CCND; however, 92
      % of patients with M0 disease had an undetectable Tg. One patient had recurrent
      DTC based on serum Tg only. CONCLUSIONS: Prophylactic CCND resulted in detection
      of unsuspected metastatic lymphadenopathy in 20 (41 %) of 49 patients and changed
      RAI recommendations in 14 (33 %). To date, most patients have an undetectable Tg.
      Longer follow-up is needed to detect potential differences in recurrent disease
      based on the use of CCND or long-term effects of RAI.

PMID- 23010733
TI  - Colorectal cancer with synchronous resectable liver metastases: monocentric
      management in a hepatobiliary referral center improves survival outcomes.
AB  - BACKGROUND: Management of patients with synchronous colorectal liver metastases
      (SCRLM) should be individually tailored. This study compares patients managed by
      hepatobiliary centers from diagnosis with those referred for liver resection
      (LR). METHODS: Between 1998 and 2010, a total of 284 patients with SCRLM
      underwent resection; 106 resectable patients (1-3 unilobar metastases, diameter
      <100 mm, liver-only disease) were divided into two groups: 66 managed from
      diagnosis (group A) and 40 referred for LR (group B). RESULTS: Group A contained
      a greater proportion of multiple metastases (55.0 vs. 34.8%, P = 0.042). Group B
      always received colorectal surgery as up-front treatment (vs. 18.2%, P < 0.0001).
      In group B, chemotherapy before LR was more common (72.5 vs. 33.3%, P = 0.0001)
      and lasted longer (P = 0.010). More patients in group B exhibited disease
      progression before LR (17.5 vs. 3.0%, P = 0.025). Group A underwent fewer
      surgical procedures (80.3% simultaneous resection vs. 0%, P < 0.00001), with
      similar short-term outcomes. After a median follow-up of 42.0 months, group A
      exhibited higher 5 year disease-free survival (DFS, 64.8 vs. 30.8%, P = 0.005)
      and fewer extrahepatic recurrences (21.5 vs. 47.5%, P = 0.005). The late-referral
      group (>6 months, n = 24) had shorter median overall survival (OS) and DFS than
      group A (49.1 and 25.3 months vs. not achieved and not achieved, P < 0.05). The
      early-referral group exhibited OS and DFS similar to group A. Multivariate
      analysis confirmed late referral as a negative predictive factor of OS and DFS.
      CONCLUSIONS: Monocentric management of SCRLM in hepatobiliary centers is
      associated with shorter preoperative chemotherapy, better disease control, fewer
      surgical procedures (simultaneous resection), and, compared with late-referred
      patients, better survival.

PMID- 23010734
TI  - Esophageal carcinosarcoma: a unique entity with better prognosis.
AB  - BACKGROUND: Esophageal carcinosarcoma is a rare kind of malignancy, and how to
      identify the patients with poor prognosis is critical for improving treatment
      efficacy and survival outcome. METHODS: The clinical characteristics, pathologic
      features, treatments, and outcomes of esophageal carcinosarcoma were analyzed in
      33 patients. Meanwhile, we hypothesized that elevated neutrophil to lymphocyte
      ratio (NLR) correlates with poor prognosis. RESULTS: Most patients had polypoid
      tumors, and the carcinomatous elements were squamous in all patients except one
      with adenosquamous carcinoma. Eight patients had elevated NLR (>=5). The median
      follow-up time was 39.1 (range, 0.5-178.2) months. The median overall survival
      time (OS) was 43.5 months, and the 1-, 3-, and 5-year OS rates were 74, 57, and
      48%, respectively. Tumor recurrence occurred in 15 patients, and the median
      relapse-free survival time (RFS) was 23.9 months, and the 2-year RFS rate was
      50%. For patients who received curative resection, OS and RFS were significantly
      associated with preoperative NLR. In the multivariate Cox regression model,
      higher NLR was an independent prognostic factor (P value was 0.001 for both OS
      and RFS). CONCLUSIONS: Our study identified the baseline NLR to be an
      independently prognostic factor for curatively resected esophageal
      carcinosarcoma.

PMID- 23010735
TI  - Application of ACOSOG Z0011 criteria reduces perioperative costs.
AB  - BACKGROUND: The ACOSOG Z0011 (Z0011) trial concluded that sentinel lymph node
      biopsy (SLNB) without completion axillary lymph node dissection (ALND) provides
      excellent regional control in women with T1-T2 sentinel lymph node (SLN) positive
      breast cancers receiving breast conservation therapy. We determined whether
      application of Z0011 guidelines would reduce costs. METHODS: A retrospective
      chart review of patients with invasive breast cancer treated with lumpectomy and
      SLNB at our institution during 2009 was performed. We determined the number of
      overnight hospital admissions following ALND and estimated costs pertaining to
      the perioperative surgical management of the axilla patients actually received,
      and compared those to the estimated number of inpatient days and perioperative
      costs if Z0011 guidelines had been followed for eligible patients. The 2011
      Medicare Fee Schedule was used to estimate costs for procedures, and costs for OR
      time were estimated using procedure length and cost of OR time per minute.
      RESULTS: A total of 71 patients underwent lumpectomy with SLNB and had at least 1
      positive SLN. Estimated costs related to perioperative surgical management of the
      axilla were $322,775, and there were 36 overnight admissions. Applying Z0011
      criteria, 51 patients (72%) would have been eligible to forego completion ALND.
      Estimated costs would have been $264,513 with 13 overnight admissions,
      translating into a cost savings of $58,262 and 23 fewer overnight admissions.
      CONCLUSION: Application of Z0011 guidelines resulted in cost savings, with a 64%
      reduction in inpatient hospital days and an 18% reduction in early perioperative
      costs.

PMID- 23010738
TI  - Thermolysis and solid state NMR studies of NaB3H8, NH3B3H7, and NH4B3H8.
AB  - In an effort to broaden the search for high-capacity hydrogen storage materials,
      three triborane compounds, NaB(3)H(8), NH(3)B(3)H(7), and NH(4)B(3)H(8), were
      studied. In addition to hydrogen, thermal decomposition also releases volatile
      boranes, and the relative amounts and species depend on the cations (Na(+),
      NH(4)(+)) and the Lewis base (NH(3)). Static-sample hydrogen NMR is used to probe
      molecular motion in the three solids. In each case, the line width decreases from
      low temperatures to room temperature in accordance with a model of isotropic or
      nearly isotropic reorientations. Such motions also explain a deep minimum in the
      relaxation time T(1). Translational diffusion never appears to be rapid on the
      10(-5) s time scale of NMR.

PMID- 23010737
TI  - Elevated CEA levels and low distance of the tumor from the anal verge are
      predictors of incomplete response to chemoradiation in patients with rectal
      cancer.
AB  - BACKGROUND: The objective of this study was to evaluate pretreatment clinical
      parameters as predictive factors for complete pathological response after long
      term chemoradiotherapy (RCT) for rectal cancer. Tumor downstaging after RCT for
      rectal cancer can be obtained in half of cases, whereas a complete pathological
      response (CPR) is reported to range between 15 and 30%. It is not possible to
      foresee before therapies who will respond. METHODS: Patients with stage II-III
      rectal cancer that had undergone RCT and rectal resection between January 1995
      and October 2010 were considered. Patients were divided in those who achieved a
      CPR, "CR" group, and those who did not achieve a CPR, "NCR" group. Univariate and
      multivariate analyses between groups were performed considering the clinical
      parameters: gender, age, ASA score, preoperative hematic CEA, tumor grading;
      distance of the tumor from the anal verge, maximum tumor diameter, TNM stage, and
      neoadjuvant treatment details. RESULTS: Among 260 patients, 43 (16.5%) achieved a
      CPR. The two groups resulted homogeneous for age, sex, pretreatment status, and
      tumor stage. A CEA <5 ng/dl and distance from anal verge >5 cm were correlated
      with CPR at multivariate analysis. Patients with both these conditions presented
      a significantly higher CPR rate (30.6%) as well as improved 5-year survival. CPR
      was also correlated with improved survival. CONCLUSIONS: Very low tumors with a
      high serum CEA are very unlikely to reach a CPR. The predictive value of these
      easily available clinical factors should not be underestimated, and better
      therapeutic strategies for these tumors are needed.

PMID- 23010736
TI  - Regulatory T cell infiltration predicts outcome following resection of colorectal
      cancer liver metastases.
AB  - BACKGROUND: Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver
      metastases (CRCLM) predict survival following resection. While CD4 and CD8 T
      cells have been correlated with outcome following CRCLM resection, the role of
      regulatory T cells (Treg) is not well defined. METHODS: TIL in 188 patients who
      underwent CRCLM resection between 1998 and 2000 were analyzed by
      immunohistochemistry using tissue microarrays. Correlation between TIL
      composition and outcome was determined while controlling for established
      prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells
      (CD8), and Treg (FoxP3) were analyzed. RESULTS: Median follow-up time was 40
      months for all patients and 95 months for survivors. Overall survival (OS) at 5
      and 10 years was 40 and 25%, respectively. The CD4 T cell count correlated with
      OS (p = .02) and recurrence-free survival (p = .04). A high number of CD8 T cells
      relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05).
      Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05)
      ratios were independent predictors of shorter OS. Patients with a high clinical
      risk score (CRS) were more likely to have a high number of intratumoral Treg, and
      patients >=65 years old had a less robust CRCLM T cell infiltration. CONCLUSIONS:
      A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome,
      suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune
      response was an independent predictor of outcome in patients with colorectal
      liver metastases.

PMID- 23010739
TI  - Independent verification of gantry angle for pre-treatment VMAT QA using EPID.
AB  - We propose a method to incorporate independent verification of gantry angle for
      electronic portal imaging device (EPID)-based pre-treatment quality assurance
      (QA) of clinical volumetric modulated arc therapy (VMAT) plans. Gantry angle is
      measured using projections in the EPID of a custom phantom placed on the couch
      and the treatment plan is modified so as to be incident on the phantom with a
      portion of the beam that is collimated in the clinical plan. For our
      implementation, collimator and couch angles were set to zero and the inferior jaw
      and two most inferior multi-leaf collimator pairs were opened for the entire QA
      delivery. A phantom containing five gold coils was used to measure the gantry
      rotation through which each portal image was acquired. We performed the EPID QA
      for ten clinical plans and evaluated accuracy of gantry angle measurement,
      scatter incident on the imager due to the phantom, inter-image pixel linearity
      and inter- and intra-image noise. The gantry angle could be measured to within
      0.0 +/- 0.3 degrees  for static gantry and 0.2 +/- 0.2 degrees  for arc
      acquisitions. Scatter due to the presence of the phantom was negligible. The
      procedure was shown to be feasible and adds gantry angle to the treatment
      planning parameters that can be verified by EPID-based pre-treatment VMAT QA.

PMID- 23010740
TI  - Helicobacter pylori protection against reflux esophagitis.
AB  - BACKGROUND AND AIM: Negative association has been reported between presence of
      Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its
      complications. The aim of this study was to determine whether H. pylori (HP) can
      be protective against GERD in an African American (AA) population. METHODS: From
      2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both
      esophagitis and gastritis (363) and a normal control group (41). We collected
      their pathology and endoscopy unit reports. HP status was determined based on
      staining of gastric biopsy. RESULTS: HP data was available for 79 % (1,611) of
      the cases. The frequency of HP positivity in gastritis patients was 40 % (506),
      in esophagitis patients 4 % and in normal controls 34 % (11), while HP was
      positive in 34 % of the patients with both esophagitis and gastritis. After
      adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01
      0.59; P value = 0.01) for the esophagitis group versus the normal group.
      CONCLUSIONS: Our results show H. pylori has a significant negative association
      with esophagitis in AAs which may point to a protective role of H. pylori in the
      pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low
      GERD complications in AAs.

PMID- 23010741
TI  - Enhanced RegIV expression predicts the intrinsic 5-fluorouracil (5-FU) resistance
      in advanced gastric cancer.
AB  - AIM: RegIV, a member of the Regenerating (REG) gene family, may be a marker for
      the prediction of resistance to 5-fluorouracil (5-FU)-based chemotherapy.
      However, the relationship between the intrinsic drug resistance of gastric cancer
      (GC) cells to 5-FU used alone (single FU) or in multidrug therapeutic regimens (5
      FU combinations) and RegIV expression has not been investigated. METHODS: The
      patient cohort comprised 45 patients with primary GC. The chemoresistance of GC
      cells to therapeutic regimens consisting of single 5-FU or FU combinations was
      investigated using the ATP-tumor chemosensitivity assay. The level of RegIV mRNA
      transcripts was determined by real-time reverse transcriptase-PCR. RegIV
      expression was evaluated as a novel predictive biomarker for the intrinsic drug
      resistance of primary GC cells to single 5-FU or 5-FU combinations. RESULTS:
      Upregulation of RegIV mRNA transcripts was observed in 36 of the 45 tumor
      specimens and was positively correlated with the invasive depth of the tumor
      cells (p = 0.000), the clinical stages (p = 0.000) and the in vitro intrinsic
      drug resistance of primary GC cells to 5-FU (p = 0.000) or 5-FU combinations.
      CONCLUSION: RegIV mRNA transcript level was strongly associated with the
      intrinsic resistance of GC cells to single 5-FU or 5-FU combinations, suggesting
      that RegIV may play an important role in the intrinsic resistance of GC cells to
      5-FU and that targeted therapy against the RegIV gene could be applied to
      overcome 5-FU resistance in the treatment of GC.

PMID- 23010742
TI  - Febuxostat improves the local and remote organ changes induced by intestinal
      ischemia/reperfusion in rats.
AB  - BACKGROUND: Xanthine oxidase has been implicated in the pathogenesis of a wide
      spectrum of diseases, and is thought to be the most important source of oxygen
      free radicals and cell damage during re-oxygenation of hypoxic tissues. AIMS: The
      present study was undertaken to demonstrate whether febuxostat is superior to
      allopurinol in prevention of the local and remote harmful effects of small
      intestinal ischemia/reperfusion injury in rats. METHODS: Intestinal ischemia was
      induced by superior mesenteric artery ligation. The rats were assigned to five
      groups: the sham control; the intestinal ischemia/reperfusion; the allopurinol;
      and the febuxostat 5 and 10 mg/kg pretreated ischemia/reperfusion groups.
      Treatment was administered from 7 days before ischemia induction. After the
      reperfusion, the serum and tissues were obtained for biochemical,
      pharmacological, and histological studies. RESULTS: Intestinal reperfusion led to
      an elevation in the serum levels of alanine aminotransferase, aspartate
      aminotransferase, tumor necrosis factor-alpha, malondialdehyde, and xanthine
      oxidase as well as intestinal myeloperoxidase, malonadialdehyde, and xanthine
      oxidase/xanthine dehydrogenase activity. Furthermore, the ischemia/reperfusion
      induced a reduction in the contractile responsiveness to acetylcholine. These
      changes were significantly regulated by the pretreatment with febuxostat compared
      to allopurinol. The degree of pathological impairment in the intestinal mucosa,
      liver, and lung tissues were lighter in the pretreated groups. CONCLUSIONS:
      Febuxostat may offer advantages over allopurinol in lessening local intestinal
      injury as well as remote hepatic and lung injuries induced by small intestinal
      ischemia/reperfusion.

PMID- 23010743
TI  - DNA methylation of NDRG2 in gastric cancer and its clinical significance.
AB  - BACKGROUND: Gastric cancer is one of the most common digestive malignancies
      worldwide. N-myc downstream-regulated gene 2 (NDRG2) is a differentiation-related
      gene that is considered to be a metastasis suppressor gene. In this study, we
      examined the expression and DNA methylation of NDRG2 in gastric cancer cell lines
      and tissues, as well as its clinical significance. METHODS: Six gastric cancer
      cell lines and 42 paired normal and gastric cancer tissue samples were used to
      assess NDRG2 mRNA expression using RT-PCR. NDRG2 DNA methylation status was
      evaluated by methylation-specific PCR (MSP) in gastric cancer cell lines and
      tissues. The suppression of NDRG2 in BGC823 cells by siRNA transfection was
      utilized to detect the role of NDRG2 in gastric cancer progression. RESULTS:
      NDRG2 mRNA was down-regulated in gastric cancer cell lines and tissues, and its
      expression was just related to lymph node metastasis (p = 0.032). MSP showed
      methylation of NDRG2 in 54.0 % (47/87) of primary gastric cancer specimens and in
      20.0 % (16/80) of corresponding nonmalignant gastric tissues. NDRG2 methylation
      was related to depth of tumor invasion, Borrmann classification and TNM stage (p
      < 0.05). Upon treatment with 5-aza-2'-deoxycytidine and trichostatin A, NDRG2
      expression was upregulated in HGC27 cells, and demethylation of the highly
      metastatic cell line, MKN45, inhibited cell invasion. Furthermore, the
      suppression of NDRG2 by siRNA transfection enhanced BGC823 cells invasion.
      CONCLUSIONS: Our results suggest that the aberrant methylation of NDRG2 may be
      mainly responsible for its downregulation in gastric cancer, and may play an
      important role in the metastasis of gastric cancer.

PMID- 23010744
TI  - Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy
      for entecavir partial responders.
AB  - BACKGROUND AND AIMS: Despite high potency, a significant proportion of patients
      treated with entecavir achieve only partial viral suppression. Our goal was to
      examine the complete viral suppression rate (undetectable HBV DNA PCR levels)
      with alternative therapies in such patients. METHODS: We retrospectively studied
      42 consecutive patients with partial response to entecavir (detectable HBV DNA at
      >=12 months of therapy) who were treated at three clinics with rescue therapies:
      entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n =
      31). Antiviral resistance was excluded by negative mutation analysis and/or
      absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir). RESULTS:
      All patients were Asian and 57 % were male with a median age of 36 (22-64) years.
      Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %).
      Almost all patients (95 %) had positive HBeAg. Overall, the complete viral
      suppression rate was 79 %, and the alanine aminotransferase normalization rate
      was 83 % in entecavir partial responders after 6 months on rescue therapies.
      Cumulative complete viral suppression rates were significantly different (P =
      0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir
      treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20
      vs. 100 vs. 97 %). All three patients without complete viral suppression on
      entecavir + adefovir became aviremic 6 months after switching to entecavir +
      tenofovir. CONCLUSIONS: Virologic response to entecavir + tenofovir combination
      therapy and tenofovir monotherapy appeared to be similar in most patients, but
      not with the entecavir + adefovir combination.

PMID- 23010745
TI  - Thrombocytopenia and bleeding in veterans with non-hepatitis C-related chronic
      liver disease.
AB  - BACKGROUND: Thrombocytopenia in chronic liver disease (CLD) typically reflects
      disease severity and may indicate an increased risk for bleeding. AIMS: To
      describe the longitudinal course of thrombocytopenia and risks for bleeding in
      veteran patients with non-hepatitis C-related CLD. METHODS: We identified 2,349
      patients with non-hepatitis C-related CLD from databases of the New England
      Veterans Healthcare System between 1999 and 2008. The cohort was stratified by
      baseline platelet counts of <50,000, 50-100,000, > 100,000-150,000, and
      >150,000/MUl. Primary outcomes were the incidence and hazard rates for bleeding
      episodes requiring hospitalization and incident severe thrombocytopenia
      (<50,000/MUl). RESULTS: Over a median follow-up of 3.3 years (IQR 1.2, 6.3),
      incident major bleeds, predominantly gastrointestinal, occurred in 254 patients
      (10.8 % of the cohort) and in 19.9 % of those with baseline platelets
      <50,000/MUl. Incident severe thrombocytopenia occurred in 315 patients (13.4 % of
      cohort) and in 40.7 % of those with baseline platelet counts between 50,000 and
      100,000/MUl. Baseline platelet counts between 50,000 and 100,000/MUl
      independently predicted bleeding [adjusted HR 2.89 (1.76, 4.73) p < 0.001] as did
      esophageal varices, hemoglobin <= 9.9 g %, and INR 1.4-2.0. Incident severe
      thrombocytopenia and minimum platelet counts <25,000/MUl each associated with
      bleeding episodes, but the average of minimum platelet counts recorded for those
      who bled was 76,000/MUl. CONCLUSIONS: Among veteran patients with non-hepatitis C
      related CLD, baseline platelet counts of 50,000 to 100,000/MUl increased
      subsequent risks for both incident severe thrombocytopenia and major bleeding
      events. Whereas associations between severe thrombocytopenia and bleeding most
      likely reflect CLD severity, liver-related coagulopathies, and co-morbid bleeding
      risks, interventions to enhance platelet production may be beneficial for such
      patients.

PMID- 23010746
TI  - Calcitonin gene-related peptide is a promising marker in ulcerative colitis.
AB  - BACKGROUND: Assessment of the severity and extent of disease activity continues
      to present challenges for physicians in the treatment of ulcerative colitis.
      Standard markers that can objectively reflect disease activity are useful for
      physicians to both evaluate the course of ulcerative colitis and monitor the
      effectiveness of therapy for any given patient. AIMS: We hypothesize that
      calcitonin gene-related peptide (CGRP) can reflect the activity and severity of
      ulcerative colitis and be used as a marker to assess the effectiveness of various
      therapies. METHODS: We examined the expression levels of CGRP by reverse
      transcription polymerase chain reaction (RT-PCR) and semi-quantitative
      immunohistochemisty in mucosal biopsies from 38 patients with UC and 18 controls.
      Levels of CGRP mRNA and protein expression were compared between patients and
      controls with the clinical activity index (CAI) and the endoscopic activity index
      (EAI) for various levels of UC severity. RESULTS: Our results showed that the
      levels of CGRP mRNA and protein expression were significantly reduced in UC
      patients compared to controls. This effect was more pronounced in patients with
      more severe cases of UC. There is a statistically significant negative
      correlation between levels of CGRP mRNA expression and CAI/EAI scores. A
      statistically significant negative correlation was also found between levels of
      CGRP protein expression and CAI/EAI scores. Overall, high CAI and EAI scores were
      accompanied by low CGRP mRNA and protein expression levels. CONCLUSION: Levels of
      CGRP protein and mRNA expression in the colonic mucosa of patients are closely
      associated with UC severity and corroborate traditional indices used to assess
      the disease.

PMID- 23010747
TI  - Quantification of early stages of cortical reorganization of the topographic map
      of V1 following retinal lesions in monkeys.
AB  - We quantified the capacity for reorganization of the topographic representation
      of area V1 in adult monkeys. Bias-free automated mapping methods were used to
      delineate receptive fields (RFs) of an array of neuronal clusters prior to, and
      up to 6 h following retinal lesions. Monocular lesions caused a significant
      reorganization of the topographic map in this area, both inside and outside the
      cortical lesion projection zone (LPZ). Small flashed stimuli revealed responses
      up to 0.85 mm inside the boundaries of the LPZ, with RFs representing regions of
      undamaged retina immediately surrounding the lesion. In contrast, long moving
      bars that spanned the scotoma resulting from the lesion revealed responsive units
      up to 1.87 mm inside the LPZ, with RFs representing interpolated responses in
      this region. This reorganization is present immediately after monocular retinal
      lesioning. Both stimuli showed a similar and significant (5-fold) increase of the
      RF scatter in the LPZ, 0.56 mm (median), compared with the undamaged retina, 0.12
      mm. Our results reveal an array of preexisting subthreshold functional
      connections of up to 2 mm in V1, which can be rapidly mobilized independently
      from the differential qualitative reorganization elicited by each stimulus. 

PMID- 23010749
TI  - Functional signalers of changes in visual stimuli: cortical responses to
      increments and decrements in motion coherence.
AB  - How does our brain detect changes in a natural scene? While changes by increments
      of specific visual attributes, such as contrast or motion coherence, can be
      signaled by an increase in neuronal activity in early visual areas, like the
      primary visual cortex (V1) or the human middle temporal complex (hMT+),
      respectively, the mechanisms for signaling changes resulting from decrements in a
      stimulus attribute are largely unknown. We have discovered opposing patterns of
      cortical responses to changes in motion coherence: unlike areas hMT+, V3A and
      parieto-occipital complex (V6+) that respond to changes in the level of motion
      coherence monotonically, human areas V4 (hV4), V3B, and ventral occipital always
      respond positively to both transient increments and decrements. This pattern of
      responding always positively to stimulus changes can emerge in the presence of
      either coherence-selective neuron populations, or neurons that are not tuned to
      particular coherences but adapt to a particular coherence level in a stimulus
      selective manner. Our findings provide evidence that these areas possess
      physiological properties suited for signaling increments and decrements in a
      stimulus and may form a part of cortical vigilance system for detecting salient
      changes in the environment. 

PMID- 23010750
TI  - Cloning, expression and biochemical characterization of a novel, moderately
      thermostable GDSL family esterase from Geobacillus thermodenitrificans T2.
AB  - A thermostable GDSL family esterase-encoding gene, EstL5, was directly obtained
      from the genomic DNA of Geobacillus thermodenitrificans T2. Recombinant
      hexahistidine-tagged EstL5 was overexpressed, purified, and its biochemical
      properties were partially characterized. EstL5 was observed to be active within
      the temperature range of 0-80 degrees C, having maximal activity at 60 degrees C.
      Unlike most other thermostable enzymes, EstL5 displayed 24% of its highest
      activity at 0 degrees C. EstL5 exhibited a high level of activity within a pH
      range of 6.0-11.0, showing the highest activity at pH 8.0. EstL5 also retained
      100% of its activity after a 12-h incubation at 55 degrees C. Furthermore, this
      enzyme was observed to be strongly inhibited by 10% (w/v) SDS and 0.1 mM PMSF.

PMID- 23010751
TI  - Clinical utility gene card for: osteogenesis imperfecta.

PMID- 23010748
TI  - A weighted and directed interareal connectivity matrix for macaque cerebral
      cortex.
AB  - Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex
      revealed 1,615 interareal pathways, a third of which have not previously been
      reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was
      determined for each area-to-area pathway. Newly found projections were weaker on
      average compared with the known projections; nevertheless, the 2 sets of pathways
      had extensively overlapping weight distributions. Repeat injections across
      individuals revealed modest FLNe variability given the range of FLNe values
      (standard deviation <1 log unit, range 5 log units). The connectivity profile for
      each area conformed to a lognormal distribution, where a majority of projections
      are moderate or weak in strength. In the G29 * 29 interareal subgraph, two-thirds
      of the connections that can exist do exist. Analysis of the smallest set of areas
      that collects links from all 91 nodes of the G29 * 91 subgraph (dominating set
      analysis) confirms the dense (66%) structure of the cortical matrix. The G29 * 29
      subgraph suggests an unexpectedly high incidence of unidirectional links. The
      directed and weighted G29 * 91 connectivity matrix for the macaque will be
      valuable for comparison with connectivity analyses in other species, including
      humans. It will also inform future modeling studies that explore the regularities
      of cortical networks.

PMID- 23010752
TI  - Familial cosegregation of rare genetic variants with disease in complex
      disorders.
AB  - Family-based designs are increasingly being used for identification of rare
      variants in complex disorders. This paper addresses two questions related to the
      utility of these designs. First, under what circumstances are rare disease
      related variants expected to cosegregate with disease in families? Second, under
      what circumstances is a disease-variant association expected to be greater in
      studies restricted to familial cases than in studies of unselected cases? To
      investigate these questions, we developed a probability model of disease
      causation involving two loci. To address cosegregation, we examined the
      probability that an affected first-degree relative of a variant-carrying proband
      would also carry the variant. We find that this probability increases with
      increasing odds ratio (OR) for the variant, but declines with increasing sibling
      recurrence risk ratio (lambdas). For example, under reasonable assumptions, the
      15q13.3 microdeletion in idiopathic generalized epilepsy, with an OR estimate of
      68 in large case-control studies, is expected to be present in >95% of affected
      first-degree relatives of variant-carrying probands. However, for a variant with
      OR=5, the probability an affected relative has the variant ranges from 82% (when
      lambdas=2) to 58% (when lambdas=50). We also find that restriction of a study to
      familial cases does not necessarily increase a rare variant's association with
      disease, especially if lambdas is high and the variant contributes little to
      overall disease familial aggregation. These findings provide guidance for the
      design of family-based studies of rare variants in complex disorders.

PMID- 23010753
TI  - A theoretical model for evaluation of the design of a hollow-fiber membrane
      oxygenator.
AB  - Geometric data are fundamental to the design of a contactor. The efficiency of a
      membrane contactor is mainly defined by its mass-transfer coefficient. However,
      design modifications also have significant effects on the performance of membrane
      contactors. In a hollow-fiber membrane oxygenator (HFMO), properties such as
      priming volume and effective membrane surface area (referred to as design
      specifications) can be determined. In this study, an extensive theoretical model
      for calculation of geometric data and configuration properties, and,
      consequently, optimization of the design of an HFMO, is presented. Calculations
      were performed for Oxyphan((r)) hollow-fiber micro-porous membranes, which are
      frequently used in current HFMOs because of their high gas exchange performance.
      The results reveal how to regulate both the transverse and longitudinal pitches
      of fiber bundles to obtain a lower rand width and a greater number of windings.
      Such modifications assist optimization of module design and, consequently,
      substantially increase the efficiency of an HFMO. On the basis of these
      considerations, three values, called efficiency factors, are proposed for
      evaluation of the design specifications of an HFMO with regard with its
      performance characteristics (i.e. oxygen-transfer rate and blood pressure drop).
      Moreover, the performance characteristics of six different commercial HFMOs were
      measured experimentally, in vitro, under the same standard conditions. Comparison
      of calculated efficiency factors reveals Quadrox((r)) is the oxygenator with the
      most efficient design with regard with its performance among the oxygenators
      tested.

PMID- 23010754
TI  - Pentraxin 3 as a new biomarker of peritoneal injury in peritoneal dialysis
      patients.
AB  - It is well known that bioincompatible peritoneal dialysate plays a central role
      in the development of peritoneal fibrosis. Peritoneal inflammation continues even
      after the cessation of peritoneal dialysate stimulation. It is important to
      establish the definition of persistent inflammation in the peritoneal cavity at
      the cessation of peritoneal dialysis (PD). The objective of the present study was
      to determine whether pentraxin 3 (PTX3) in peritoneal effluent (PE) may be a new
      biomarker in PD patients. Serum, PE, and peritoneal specimens were obtained from
      50 patients with end-stage kidney disease at Juntendo University Hospital.
      Samples of 19 patients were obtained at the initiation of PD and those of 31
      patients at the cessation of PD. PTX3, high-sensitivity CRP, and MMP-2 and IL-6
      were analyzed. An immunohistological examination using an anti-PTX3 antibody was
      performed. Expressions of PTX3 were observed in endothelial cells, fibroblasts,
      and mesothelial cells in the peritoneum. The PTX3 level in PE at the cessation of
      PD was significantly higher than that at the initiation of PD. Effluent PTX3
      levels in patients with a history of peritonitis or a PD duration of more than 8
      years were significantly higher than those in patients without peritonitis or
      patients with a PD duration of <8 years. The PTX3 level was significantly
      correlated with MMP-2 and IL-6 levels in PE, as well as the thickness of the
      submesothelial compact zone and the vasculopathy. It appears that PTX3 may be a
      new biomarker of peritoneal inflammation and progressive fibrosis.

PMID- 23010755
TI  - Age related changes in gene expression within the cochlea of C57BL/6J mice.
AB  - BACKGROUND AND AIMS: Hearing loss as a unique symptom is highly prevalent in the
      elderly and while there exists several pathologies that would result in age
      related hearing loss (ARHL), most agree it is multifactorial with environmental,
      metabolic and genetic components. However, no research to date has discovered a
      definitive genetic cause. This paper describes the use of microarray to address
      this issue. METHODS: The left cochlea of laboratory aged C57BL6J mice at 4, 15
      and 45 weeks was extracted from pooled, agematched animals and the RNA extracted
      for use in microarray analysis. The contralateral cochlea was also removed and
      used for immunohistochemical analysis. RESULTS: Microarray revealed 116 genes to
      be up or down regulated between young and old animals, the most prominent being
      prolactin (108.2 fold increase) and growth hormone (43.94 fold increase). The
      prolactin inhibitor calcitonin was also down regulated over 2 fold.
      Immunohistochemistry revealed prolactin to be weakly expressed within the spiral
      ganglion, whilst its receptor was widely distributed throughout the cochlea.
      CONCLUSION: This is the first study demonstrating the cochlea as a site for
      extrapituitary prolactin expression and that this expression is related to age.
      Combined with the widespread distribution of prolactin receptor, there may be
      implications for prolactin's role in ARHL.

PMID- 23010756
TI  - Comprehensive characterization and failure modes of tungsten microwire arrays in
      chronic neural implants.
AB  - For nearly 55 years, tungsten microwires have been widely used in
      neurophysiological experiments in animal models to chronically record neuronal
      activity. While tungsten microwires initially provide stable recordings, their
      inability to reliably record high-quality neural signals for tens of years has
      limited their efficacy for neuroprosthetic applications in humans. Comprehensive
      understanding of the mechanisms of electrode performance and failure is necessary
      for developing next generation neural interfaces for humans. In this study, we
      evaluated the abiotic (electrophysiology, impedance, electrode morphology) and
      biotic (microglial reactivity, blood-brain barrier disruption, biochemical
      markers of axonal injury) effects of 16-channel, 50 um diameter, polyimide
      insulated tungsten microwires array for implant durations that ranged from acute
      to up to 9 months in 25 rats. Daily electrode impedance spectroscopy,
      electrophysiological recordings, blood and cerebrospinal fluid (CSF) withdrawals,
      and histopathological analysis were performed to study the time-varying effects
      of chronic electrode implantation. Structural changes at the electrode recording
      site were observed as early as within 2-3 h of electrode insertion. Abiotic
      analysis indicated the first 2-3 weeks following surgery was the most dynamic
      period in the chronic electrode lifetime as there were greater variations in the
      electrode impedance, functional electrode performance, and the structural changes
      occurring at the electrode recording tips. Electrode recording site deterioration
      continued for the long-term chronic animals as insulation damage occurred and
      recording surface became more recessed over time. In general, electrode impedance
      and functional performance had smaller daily variations combined with reduced
      electrode recording site changes during the chronic phase. Histopathological
      studies were focused largely on characterizing microglial cell responses to
      electrode implantation. We found that activated microglia were present near the
      electrode tracks in all non-acute animals studied, thus indicating presence of a
      neuroinflammatory response regardless of post-implantation survival times and
      electrode performance. Conversely, dystrophic microglia detectable as fragmented
      cells were found almost exclusively in acute animals surviving only few hours
      after implantation. While there was no consistent relationship between microglial
      cell responses and electrode performance, we noticed co-occurrence of high
      ferritin expression, intraparenchymal bleeding, and microglial degeneration
      suggesting presence of excessive oxidative stress via Fenton chemistry.
      Biochemical analysis indicated that these electrodes always caused a persistent
      release of axonal injury biomarkers even several months after implantation
      suggesting persistent tissue damage. Our study suggests that mechanisms of
      electrode failure are multi-factorial involving both abiotic and biotic
      parameters. Since these failure modes occur concurrently and cannot be isolated
      from one another, the lack of consistent relationship between electrode
      performance and microglial responses in our results suggest that one or more of
      the abiotic factors were equally responsible for degradation in electrode
      performance over long periods of time.

PMID- 23010757
TI  - Predicting progression to chronic kidney disease after recovery from acute kidney
      injury.
AB  - PURPOSE OF REVIEW: This review examines the association between acute kidney
      injury (AKI) and subsequent risk for chronic kidney disease (CKD) development.
      The discussion focuses on patients who fully recover from an episode of AKI, the
      majority of whom do not receive follow-up care with nephrology services. RECENT
      FINDINGS: Several studies have demonstrated a strong association between AKI and
      later CKD risk. Animal models provide evidence for a causal link between AKI and
      CKD while also elucidating some of the potential mechanisms for this progression.
      Large observational studies have quantified the risk of CKD following AKI
      recovery, and clinical and emerging biomarker risk factors have been identified.
      SUMMARY: The association between AKI with incomplete recovery or nonrecovery and
      CKD is evident. Recent studies demonstrate that even AKI with apparent full
      recovery confers an increased risk for subsequent CKD development. Risk
      prediction models have been developed and require further refinement and
      validation. The ability to identify patients with AKI recovery who are at high
      risk for later CKD development is an important clinical and research goal, as
      there exists a significant opportunity to improve care in this population.

PMID- 23010758
TI  - Assessment of obesity in chronic kidney disease:  what is the best measure?
AB  - PURPOSE OF REVIEW: Obesity is a major driver of the current epidemic of chronic
      kidney disease (CKD), but metrics of obesity in the CKD population have been
      studied sparsely. This review updates knowledge on this issue. RECENT FINDINGS:
      Measures of abdominal obesity, waist circumference and waist-to-hip ratio (WHR),
      are better predictors than BMI of the high risk of mortality in predialysis and
      dialysis patients and waist circumference reliably reflects visceral fat in CKD
      patients. Skinfold thickness and WHR are superior to BMI for the classification
      of obesity in CKD patients. Multifrequency body impedance analysis (BIA) provides
      valid estimates of fat mass in hemodialysis patients. SUMMARY: Skinfold
      thickness,WHR and multifrequency BIA are superior to BMI for measuring body fat
      in CKD patients and measures of abdominal obesity are stronger predictors of
      adverse clinical outcomes than the BMI. These metrics should be preferentially
      applied for the assessment of obesity in CKD, but it remains unproven that these
      techniques offer real advantages over the BMI in clinical practice in CKD
      patients.

PMID- 23010759
TI  - Chronic kidney disease 10 years on:  what have we learned?
AB  - PURPOSE OF REVIEW: The aim is to review in broad terms the rapid growth in
      knowledge and understanding of chronic kidney disease in the key areas of
      epidemiology, diagnosis and risk prediction in the 10 years since publication of
      the first formal definition and classification. RECENT FINDINGS: Epidemiological
      studies that utilized the MDRD equation to estimate glomerular filtration rate
      (GFR) identified that chronic kidney disease (CKD) was more prevalent than
      previously appreciated. Considerable effort has been invested in developing more
      accurate formulae to estimate GFR from serum creatinine and/or cystatin C. There
      is a growing appreciation of the increased risk of cardiovascular disease and
      death associated with even small reductions in GFR or mild albuminuria. Risk
      prediction equations have been developed to assess risk of progression of CKD but
      these require further validation, and equations to predict the cardiovascular
      risk associated with CKD are urgently required. SUMMARY: The first 10 years of
      'CKD' have been characterized by an unprecedented growth in knowledge and
      understanding but over the next decade efforts should focus on translating this
      enhanced knowledge into improved outcomes for the many people now living with
      this diagnosis.

PMID- 23010760
TI  - CKD impairs barrier function and alters microbial flora of the intestine:  a
      major link to inflammation and uremic toxicity.
AB  - PURPOSE OF REVIEW: Chronic kidney disease (CKD) is associated with oxidative
      stress and inflammation which contribute to progression of kidney disease and its
      numerous complications. Until recently, little attention had been paid to the
      role of the intestine and its microbial flora in the pathogenesis of CKD
      associated inflammation. This article is intended to provide an over view of the
      impact of uremia on the structure and function of the gut and its microbial flora
      and their potential link to the associated systemic inflammation. RECENT
      FINDINGS: Recent studies conducted in the author's laboratories have demonstrated
      marked disintegration of the colonic epithelial barrier structure and significant
      alteration of the colonic bacterial flora in humans and animals with advanced
      CKD. The observed disruption of the intestinal epithelial barrier complex can
      play an important part in the development of systemic inflammation by enabling
      influx of endotoxin and other noxious luminal contents into the systemic
      circulation. Similarly via disruption of the normal symbiotic relationship and
      production, absorption and retention of noxious products, alteration of the
      microbial flora can contribute to systemic inflammation and uremic toxicity. In
      fact recent studies have documented the role of colonic bacteria as the primary
      source of several well known pro-inflammatory/pro-oxidant uremic toxins as well
      as many as-yet unidentified retained compounds. SUMMARY: CKD results in
      disruption of the intestinal barrier structure and marked alteration of its
      microbial flora - events that play a major role in the pathogenesis of
      inflammation and uremic toxicity.

PMID- 23010761
TI  - MRI for the assessment of organ perfusion in patients with chronic kidney
      disease.
AB  - PURPOSE OF REVIEW: Recent data have highlighted the importance of quantitative
      measures of organ perfusion and functional reserve. Magnetic resonance imaging
      allows the assessment of markers of perfusion without the use of contrast media.
      Techniques such as arterial spin labelling (ASL) and blood oxygen level-dependent
      (BOLD) imaging have been available for some time, but advances in the technology
      and concerns over the safety of contrast media in renal disease have spurred
      renewed interest and development. RECENT FINDINGS: ASL measures perfusion,
      whereas BOLD imaging provides a marker of blood oxygenation, arising from the
      compound effect of a number of measures including perfusion, blood volume and
      oxygen consumption; thus, the techniques are complementary rather than analogous.
      They were initially confined to brain imaging as inherently low signal,
      susceptibility effects and motion limited their use in thoracic and abdominal
      organs. Advances in technology have led to robust sequences that can quantify
      clinically relevant changes and correlate well with reference standards. Novel
      approaches are likely to accelerate translation into clinical practice. SUMMARY:
      The noninvasive and repeatable nature of ASL and BOLD imaging makes it likely
      that they will be increasingly used in clinical research. Using a developmental
      framework, we suggest that the application of these techniques to thoracic and
      abdominal organs requires validation before they are suitable for generalized
      clinical use. The demand for these techniques is likely to be driven by the
      incentive to avoid the use of contrast media.

PMID- 23010763
TI  - Gait pattern and lower extremity alignment in children with Morquio syndrome.
AB  - The gait in children with Morquio syndrome (MPS IV) has not been previously
      described. We reviewed the charts, gait analysis reports, and radiographs of nine
      children with no previous lower extremity surgery. Children with MPS IV had a
      slower walking speed, reduced cadence, and reduced stride length as compared with
      normal (P<0.05). There was increased knee flexion, genu valgus, and external
      tibial torsion during stance (P<0.05). Kinetics showed that knee varus moment was
      increased (P<0.05). There was a strong correlation between genu valgus measured
      on gait analysis and standing radiographs (r=0.89).

PMID- 23010762
TI  - Proximal tubule angiotensinogen modulation of arterial pressure.
AB  - PURPOSE OF REVIEW: Although the existence of a complete intrarenal renin
      angiotensin system is now well established, its role in modulating tubule sodium
      transport and blood pressure is incompletely understood. Several recent studies
      have shed light on one component of the system, proximal tubule-derived
      angiotensinogen (AGT). This review discusses the synthesis, regulation and
      function of AGT in the proximal tubule. RECENT FINDINGS: Under normal sodium
      intake, AGT within the S1 and S2 segments of the proximal tubule may derive from
      the systemic circulation, whereas the S3 segment synthesizes AGT. Urinary AGT
      likely primarily reflects proximal tubule-derived AGT. Proximal tubule AGT
      synthesis is regulated by high Na intake, angiotensin-II and inflammatory
      cytokines. Transgenic expression of mouse AGT in the proximal tubule causes
      hypertension. Overexpression of rat AGT in the proximal tubule leads to
      hypertension, enhanced reactive oxygen species generation via NADPH oxidase,
      tubular apoptosis and tubulointerstitial fibrosis; these effects can be mitigated
      by catalase overexpression. SUMMARY: Proximal tubule-derived AGT has the
      potential to modulate blood pressure and sodium balance, and promote renal
      injury. Interactions with the systemic renin-angiotensin system may influence the
      role of proximal tubule-derived AGT in the kidney.

PMID- 23010764
TI  - Hydrophobicity/hydrophilicity tunable hyperbranched polystyrenes as novel
      supports for transition-metal nanoparticles.
AB  - Development of a new preparative procedure for hyperbranched polystyrene having
      Cl end groups (HPS-Cl) enables to prepare HPS-NR(3)(+)Cl(-), for which the
      hydrophobicity/hydrophilicity is tunable by the R groups. The resulting ammonium
      salts behave as a good support of platinum nanoparticles, which is useful for
      catalytic biphasic hydrogenation of alkenes.

PMID- 23010765
TI  - The associative and limbic thalamus in the pathophysiology of obsessive
      compulsive disorder: an experimental study in the monkey.
AB  - Obsessive-compulsive disorder (OCD) is a frequent psychiatric disorder
      characterized by repetitive intrusive thoughts and severe anxiety, leading to
      compulsive behaviors. Although medical treatment is effective in most cases,
      resistance is observed in about 30% of patients. In this context, deep brain
      stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed
      with encouraging results. However, some patients were unimproved or exhibited
      awkward side effects. Therefore, exploration of new targets for DBS remains
      critical in OCD. In the latter, functional imaging studies revealed overactivity
      in the limbic and associative cortico-subcortical loops encompassing the
      thalamus. However, the role of the thalamus in the genesis of repetitive
      behaviors and related anxiety is unknown. Here, we tested the hypothesis that
      pharmacological-induced overactivity of the medial thalamus could give rise to
      abnormal behaviors close to that observed in OCD. We modulated the ventral
      anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline
      (GABA(A) antagonist) microinjections in subhuman primates and assessed their
      pharmacological-induced behavior. Bicuculline injections within the VA caused
      significant repetitive and time-consuming motor acts whereas those performed
      within the MD induced symptoms of dysautonomic dysregulation along with abnormal
      vocalizations and marked motor hypoactivity. These findings suggest that
      overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like
      behaviors and neurovegetative manifestations usually associated with the feeling
      of anxiety in OCD patients. In further research, this translational approach
      should allow us to test the effectiveness and side effects of these thalamic
      nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this
      technique to severely disabled OCD patients.

PMID- 23010766
TI  - Failure to extinguish fear and genetic variability in the human cannabinoid
      receptor 1.
AB  - Failure to extinguish fear can lead to persevering anxiety and has been
      postulated as an important mechanism in the pathogenesis of human anxiety
      disorders. In animals, it is well documented that the endogenous cannabinoid
      system has a pivotal role in the successful extinction of fear, most importantly
      through the cannabinoid receptor 1. However, no human studies have reported a
      translation of this preclinical evidence yet. Healthy medication-free human
      subjects (N=150) underwent a fear conditioning and extinction procedure in a
      virtual reality environment. Fear potentiation of the eyeblink startle reflex was
      measured to assess fear-conditioned responding, and subjective fear ratings were
      collected. Participants were genotyped for two polymorphisms located within the
      promoter region (rs2180619) and the coding region (rs1049353) of cannabinoid
      receptor 1. As predicted from the preclinical literature, acquisition and
      expression of conditioned fear did not differ between genotypes. Crucially,
      whereas both homozygote (G/G, N=23) and heterozygote (A/G, N=68) G-allele
      carriers of rs2180619 displayed robust extinction of fear, extinction of fear
      potentiated startle was absent in A/A homozygotes (N=51). Additionally, this
      resistance to extinguish fear left A/A carriers of rs2180619 with significantly
      higher levels of fear-potentiated startle at the end of the extinction training.
      No effects of rs1049353 genotype were observed regarding fear acquisition and
      extinction. These results suggest for the first time involvement of the human
      endocannabinoid system in fear extinction. Implications are that genetic
      variability in this system may underlie individual differences in anxiety,
      rendering cannabinoid receptor 1 a potential target for novel pharmacological
      treatments of anxiety disorders.

PMID- 23010769
TI  - Displaying 3D radiation dose on endoscopic video for therapeutic assessment and
      surgical guidance.
AB  - We have developed a method to register and display 3D parametric data, in
      particular radiation dose, on two-dimensional endoscopic images. This
      registration of radiation dose to endoscopic or optical imaging may be valuable
      in assessment of normal tissue response to radiation, and visualization of
      radiated tissues in patients receiving post-radiation surgery. Electromagnetic
      sensors embedded in a flexible endoscope were used to track the position and
      orientation of the endoscope allowing registration of 2D endoscopic images to CT
      volumetric images and radiation doses planned with respect to these images. A
      surface was rendered from the CT image based on the air/tissue threshold,
      creating a virtual endoscopic view analogous to the real endoscopic view.
      Radiation dose at the surface or at known depth below the surface was assigned to
      each segment of the virtual surface. Dose could be displayed as either a
      colorwash on this surface or surface isodose lines. By assigning transparency
      levels to each surface segment based on dose or isoline location, the virtual
      dose display was overlaid onto the real endoscope image. Spatial accuracy of the
      dose display was tested using a cylindrical phantom with a treatment plan created
      for the phantom that matched dose levels with grid lines on the phantom surface.
      The accuracy of the dose display in these phantoms was 0.8-0.99 mm. To
      demonstrate clinical feasibility of this approach, the dose display was also
      tested on clinical data of a patient with laryngeal cancer treated with radiation
      therapy, with estimated display accuracy of ~2-3 mm. The utility of the dose
      display for registration of radiation dose information to the surgical field was
      further demonstrated in a mock sarcoma case using a leg phantom. With direct
      overlay of radiation dose on endoscopic imaging, tissue toxicities and tumor
      response in endoluminal organs can be directly correlated with the actual tissue
      dose, offering a more nuanced assessment of normal tissue toxicities following
      radiation therapy and accurate registration of radiation dose to the surgical
      field.

PMID- 23010768
TI  - Genome-wide significant association between a 'negative mood delusions' dimension
      in bipolar disorder and genetic variation on chromosome 3q26.1.
AB  - Research suggests that clinical symptom dimensions may be more useful in
      delineating the genetics of bipolar disorder (BD) than standard diagnostic
      models. To date, no study has applied this concept to data from genome-wide
      association studies (GWAS). We performed a GWAS of factor dimensions in 927
      clinically well-characterized BD patients of German ancestry. Rs9875793, which is
      located in an intergenic region of 3q26.1 and in the vicinity of the solute
      carrier family 2 (facilitated glucose transporter), member 2 gene (SLC2A2), was
      significantly associated with the factor analysis-derived dimension 'negative
      mood delusions' (n=927; P=4.65 * 10(-8), odds ratio (OR)=2.66). This dimension
      was comprised of the symptoms delusions of poverty, delusions of guilt and
      nihilistic delusions. In case-control analyses, significant association with the
      G allele of rs9875793 was only observed in the subgroup of BD patients who
      displayed symptoms of 'negative mood delusions' (allelic chi(2) model:
      P(G)=0.0001, OR=1.92; item present, n=89). Further support for the hypothesis
      that rs9875793 is associated with BD in patients displaying 'negative mood
      delusions' symptom, such as delusions of guilt, was obtained from an European
      American sample (GAIN/TGEN), which included 1247 BD patients and 1434 controls
      (P(EA)=0.028, OR=1.27).

PMID- 23010770
TI  - A 13C and 1H NMR spectroscopic investigation of the structure of the iminium ion
      with a dipolar form in metal complexes of 2-N-substituted N-confused porphyrins.
AB  - The crystal structures of chloro(2-aza-2-ethoxycarbonylmethyl-5,10,15,20
      tetraphenyl-21-carbaporphyrinato-N,N'N'') zinc(II) [Zn(2-NCH2COOC2H5NCTPP)Cl; 4],
      (2-aza-2-ethoxycarbonylmethyl-5,10,15,20-tetraphenyl-21-carbaporphyrinato
      N,N'N'') palladium(II) [Pd(2-NCH2COOC2H5NCTPP); 5], bromo(2-aza-2
      ethoxycarbonylmethyl-5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N'')
      manganese(III) [Mn(2-NCH2COOC2H5NCTPP)Br; 6], [2-aza-(3'-phenoxypropyl)
      5,10,15,20-tetraphenyl-21-carbaporphyrinato-N,N'N''] nickel(II) [Ni(2
      NCH2CH2CH2OC6H5NCTPP); 7] and chloro(2-aza-2-methoxycarbonylmethyl-5,10,15,20
      tetraphenyl-21-carbaporphyrinato-N,N'N'') zinc(II) [Zn(2-NCH2COOCH3NCTPP)Cl; 8]
      have been established. The g value of 9.54, which was measured from the parallel
      polarization of the X-band EPR spectra in CHCl3 at 4 K, is consistent with the
      high spin mononuclear manganese(III) centre (S = 2) in 6. The magnitude of the
      axial (D) zero-field splitting (ZFS) for the mononuclear Mn(III) centre in 6 was
      determined approximately to be 1.63 cm(-1) by paramagnetic susceptibility
      measurements. The NMR spectroscopic investigation of the iminium ion with a
      dipolar canonical contribution to the metal complexes 5-7, Pd(2-NCH2C6H5NCTPP)
      (10) and Ni(2-NCH2C6H5NCTPP) (11) in CDCl3 is reported. A resonance between the
      dipolar canonical form II and covalent canonical form I exists for complexes 5-7,
      10 and 11 in CDCl3. To develop the correlations between delta13C [C(3)], delta1H
      [H(3)] and the canonical form II in 5-7, 10 and 11, this work thoroughly examines
      the 13C and 1H NMR of N+=CH(Ar) fragment on seven metal complexes of 2-N
      substituted N-confused porphyrin. According to these results, the 13C [C(3)] and
      1H [H(3)] chemical shifts of the N+=CH(Ar) fragment at 20  degrees C in CDCl3 are
      separately located at 152.6 +/- 0.5 and 8.30 +/- 0.15 ppm respectively for the
      iminium ion. This exists as a dipolar canonical form II for complexes 5-7, 10 and
      11, and the N-CH(Ar) group appears at 121.1 +/- 0.1 ppm and 6.35 +/- 0.01 ppm,
      which is in a covalent canonical form I contribution to complexes 4 and 8. X-Ray
      diffraction data indicate that N(2)-C(3) = 1.315 +/- 0.011 A for the dipolar
      contribution of 5-7, 10-13, while N(2)-C(3) = 1.331 +/- 0.008 A for the covalent
      contribution of 4 and 8.

PMID- 23010771
TI  - Self-paced brain-computer interface control of ambulation in a virtual reality
      environment.
AB  - OBJECTIVE: Spinal cord injury (SCI) often leaves affected individuals unable to
      ambulate. Electroencephalogram (EEG) based brain-computer interface (BCI)
      controlled lower extremity prostheses may restore intuitive and able-body-like
      ambulation after SCI. To test its feasibility, the authors developed and tested a
      novel EEG-based, data-driven BCI system for intuitive and self-paced control of
      the ambulation of an avatar within a virtual reality environment (VRE). APPROACH:
      Eight able-bodied subjects and one with SCI underwent the following 10-min
      training session: subjects alternated between idling and walking kinaesthetic
      motor imageries (KMI) while their EEG were recorded and analysed to generate
      subject-specific decoding models. Subjects then performed a goal-oriented online
      task, repeated over five sessions, in which they utilized the KMI to control the
      linear ambulation of an avatar and make ten sequential stops at designated points
      within the VRE. MAIN RESULTS: The average offline training performance across
      subjects was 77.2 +/- 11.0%, ranging from 64.3% (p = 0.001 76) to 94.5% (p = 6.26
      * 10(-23)), with chance performance being 50%. The average online performance was
      8.5 +/- 1.1 (out of 10) successful stops and 303 +/- 53 s completion time
      (perfect = 211 s). All subjects achieved performances significantly different
      than those of random walk (p < 0.05) in 44 of the 45 online sessions.
      SIGNIFICANCE: By using a data-driven machine learning approach to decode users'
      KMI, this BCI-VRE system enabled intuitive and purposeful self-paced control of
      ambulation after only 10 minutes training. The ability to achieve such BCI
      control with minimal training indicates that the implementation of future BCI
      lower extremity prosthesis systems may be feasible.

PMID- 23010772
TI  - An exercise-based physical therapy program for patients with patellar
      tendinopathy after platelet-rich plasma injection.
AB  - OBJECTIVES: To describe a post platelet-rich plasma (PRP) injection, exercise
      based physical therapy program, investigate feasibility and report the first
      results of patellar tendinopathy patients treated with PRP injection combined
      with the physical therapy program. STUDY DESIGN: Case-series. SETTING: A PRP
      injection followed by a physical therapy program seems promising for the
      treatment of patellar tendinopathy. However, descriptions of physical therapy
      programs are often limited and incomplete. PARTICIPANTS: Five patellar
      tendinopathy patients (six tendons) in the degenerative phase. MAIN OUTCOME
      MEASURE: VISA-P score. RESULTS: Muscle strength, endurance, power and retraining
      sport-specific function form the basis for the physical therapy program aiming to
      improve the load capacity of the knee. The program is characterised by gradually
      increasing intensity and difficulty of exercises. Five of the six tendons showed
      an improvement of at least 30 points on the VISA-P after 26 weeks. CONCLUSIONS:
      This study extensively describes, based on current knowledge, a physical therapy
      program after PRP injection for patellar tendinopathy patients. The combination
      treatment reported in this study is feasible and seems to be promising for
      patients in the late/degenerative phase of patellar tendinopathy.

PMID- 23010773
TI  - Adverse effects of peg-Interferon and Ribavirin combined antiviral treatment in a
      Romanian hepatitis C virus infected cohort.
AB  - INTRODUCTION: Adverse effects appearing during combined peg-Interferon and
      Ribavirin antiviral treatment against chronic infection with the hepatitis C
      virus are a major cause for treatment failures and abrupt interruption. In the
      prospect of the imminent introduction of new direct acting antiviral agents, with
      demonstrated higher rates of adverse effects, our study aimed to assess the
      severity and incidence of several types of adverse effects in a cohort of
      genotype 1 infected Romanian patients. MATERIALS AND METHODS: We prospectively
      included a total of 150 patients (45 men), aged 25 to 64 years, who received
      combined peg-Interferon and Ribavirin antiviral treatment for chronic hepatitis
      C. Out of these, 145 patients also had liver biopsies prior to treatment
      initiation. We recorded their viral loads, hemoglobin values and thrombocyte
      counts, as well as any dermatological, psychiatric or constitutional adverse
      effect after twelve doses, eight and twelve months of treatment, with two follow
      up examinations at three and six months after treatment completion. RESULTS:
      Viral loads significantly decreased after 12 doses of treatment, in the end a
      total of six patients (two men and four women) being declared non-responders.
      Hemoglobin values and thrombocyte counts significantly decreased during treatment
      (p<0.0001), with their values being restored to pre-treatment levels during the
      follow-up period. We did not find significant differences between the 12-doses, 8
      and 12 months values during treatment (p>0.05). We recorded 43 cases (11 men and
      32 women) presenting with rashes, drug eruptions and erythema. We only
      encountered grade 1 and 2 dermatological adverse effects. Psychiatric effects
      were present in 34 cases (10 men and 24 women, 22.6% of the group) and manifested
      as mild depressions, which did not require specific medication or antiviral dose
      adjustment. Patients also presented headaches (80.6%), fatigue (71.3%), nausea
      (47.3%), arthralgias (35.3%) and fever (30%). CONCLUSIONS: We did not encounter
      severe hematological adverse effects that would require Ribavirin dosage
      adjustments. Cutaneous and psychiatric adverse effects were also present in a
      significant number of patients; however, their severity did not influence the
      continuity or outcome of the antiviral treatment. Other constitutional effects
      were also present with no direct consequence on the course of treatment. Future
      agents employed in antiviral therapy shall require extensive monitoring of all
      adverse effects already acknowledged during dual combination therapy.

PMID- 23010774
TI  - Understanding biocompatibility:  the importance of study design, methods, and
      proper interpretation.

PMID- 23010775
TI  - Reply. Intraoperative corneal thickness measurements during corneal collagen
      cross-linking with hypoosmolar riboflavin solution in thin corneas.

PMID- 23010776
TI  - Intraocular lens calcification after keratoplasty.
AB  - PURPOSE: To report calcification of intraocular lenses (IOLs) after various
      keratoplasty procedures. METHODS: Clinical data of all cases with calcified IOLs
      after keratoplasty procedures were analyzed. A total of 6 explanted IOLs were
      analyzed with light microscopy before and after staining with 1% alizarin red and
      the von Kossa method. RESULTS: A total of 7 cases occurred after Descemet
      stripping automated endothelial keratoplasty, 1 case after deep anterior lamellar
      keratoplasty, and 2 cases after penetrating keratoplasty. Median time interval
      from keratoplasty to first notice of IOL opacification was 6.5 months (minimum 3
      months, maximum 51 months). A total of 3 IOLs had been placed at the time of
      keratoplasty and 7 IOLs before keratoplasty. All affected IOLs were hydrophilic
      acrylic and comprised IOLs from at least 3 different polymer sources. Common
      clinical aspects were some amount of inflammation in the anterior chamber during
      the postoperative period and use of air at the end of surgery in 8 of the 10
      cases. Histochemical analysis demonstrated the presence of fine granular deposits
      located within the very superficial optic material in all cases. The deposits
      stained positive for calcium with alizarin red and the von Kossa method.
      CONCLUSIONS: IOL calcification associated with keratoplasty in our series does
      not seem to be a problem related to a specific IOL model or polymer. The process
      of calcification may be mediated by inflammation, which also may be related to
      multiple injections of air into the anterior chamber.

PMID- 23010777
TI  - 3'-UTRs as a source of regulatory RNAs in bacteria.
AB  - Bacterial small non-coding RNAs, sRNAs, have up to now been identified primarily
      in intergenic regions. Chao et al reveal that the 3'-region of mRNAs is another
      rich reservoir of sRNAs.

PMID- 23010779
TI  - Diet type and changes in food cravings following weight loss: findings from the
      POUNDS LOST Trial.
AB  - Few well-controlled trials have evaluated the effects that macronutrient
      composition has on changes in food cravings during weight loss treatment. The
      present study, which was part of the Preventing Overweight Using Novel Dietary
      Strategies (POUNDS LOST) trial, investigated whether the fat and protein content
      of four different diets affected changes in specific food cravings in overweight
      and obese adults. A sample of 811 adults were recruited across two clinical
      sites, and each participant was randomly assigned to one of four macronutrient
      prescriptions: 1) low fat (20% of energy), average protein (15% of energy); 2)
      moderate fat (40%), average protein (15%); 3) low fat (20%), high protein (25%);
      4) moderate fat (40%), high protein (25%). With few exceptions, the type of diet
      that participants were assigned did not differentially affect changes in specific
      food cravings. Participants assigned to the high-fat diets, however, had reduced
      cravings for carbohydrates at month 12 (p<0.05) and fruits and vegetables at
      month 24. Also, participants assigned to high-protein diets had increased
      cravings for sweets at month 6 and month 12 (ps<0.05). Participants in all four
      dietary conditions reported significant reductions in food cravings for specific
      types of foods (i.e., high fat foods, fast food fats, sweets, and
      carbohydrates/starches; all ps<0.05). Cravings for fruits and vegetables,
      however, were increased at month 24 (p<0.05). Calorically restricted diets
      (regardless of their macronutrient composition) yielded significant reductions in
      cravings for fats, sweets, and starches whereas cravings for fruits and
      vegetables were increased.

PMID- 23010778
TI  - A role for CTCF and cohesin in subtelomere chromatin organization, TERRA
      transcription, and telomere end protection.
AB  - The contribution of human subtelomeric DNA and chromatin organization to telomere
      integrity and chromosome end protection is not yet understood in molecular
      detail. Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF-
      and cohesin-binding site within ~1-2 kb of the TTAGGG repeat tract and adjacent
      to a CpG-islands implicated in TERRA transcription control. ChIP-Seq also
      revealed that RNA polymerase II (RNAPII) was enriched at sites adjacent to the
      CTCF sites and extending towards the telomere repeat tracts. Mutation of CTCF
      binding sites in plasmid-borne promoters reduced transcriptional activity in an
      orientation-dependent manner. Depletion of CTCF by shRNA led to a decrease in
      TERRA transcription, and a loss of cohesin and RNAPII binding to the
      subtelomeres. Depletion of either CTCF or cohesin subunit Rad21 caused telomere
      induced DNA damage foci (TIF) formation, and destabilized TRF1 and TRF2 binding
      to the TTAGGG proximal subtelomere DNA. These findings indicate that CTCF and
      cohesin are integral components of most human subtelomeres, and important for the
      regulation of TERRA transcription and telomere end protection.

PMID- 23010780
TI  - Body dissatisfaction is improved but the ideal silhouette is unchanged during
      weight recovery in anorexia nervosa female inpatients.
AB  - OBJECTIVE: Few studies have examined the impact of weight gain on body image
      disturbance (BID) in patients suffering from anorexia nervosa (AN). This study
      aims to explore the evolution of body distortion and body dissatisfaction
      following inpatient treatment. METHOD: Sixty-four women suffering from AN
      enrolled in our inpatient Cognitive and Behavioural Therapy programme and
      undertook a body image perception test and completed the Eating Disorder
      Inventory (EDI). Thirty-four participants completed a total of four evaluations
      over a three-month period. RESULTS: Patients' weight gain following treatment was
      significant. Weight regain was accompanied by significant reductions in both body
      distortion and body dissatisfaction. These reductions were complemented by
      improved scores for both EDI Drive for Thinness and Body Dissatisfaction.
      Perceived body image differed significantly between the onset and the completion
      of inpatient treatment whereas ideal body image did not. DISCUSSION: The high
      severity of the included patients and the significant attrition rate should limit
      our conclusions for a subgroup of patients. New approaches are needed to
      facilitate changes in the way patients assess their ideal body image.

PMID- 23010781
TI  - Body dissatisfaction among pre-adolescent girls is predicted by their involvement
      in aesthetic sports and by personal characteristics of their mothers.
AB  - Empirical evidence indicates that the dissatisfaction with one's body is widely
      present in the general population even at very early ages, and that it is
      predictive of future eating disorders. The family seem particularly influent for
      the development of body dissatisfaction while sports practice is associated to a
      higher prevalence of disordered eating. However the role of sports practice in
      the development of body dissatisfaction is still under debate and only few
      studies have evaluated together the influences of family and sport practice on
      body dissatisfaction. The present study aimed at evaluating both the singular and
      conjoint role of the type of sport and maternal influences in young female
      children. The sport influence was assessed comparing aesthetic and non-aesthetic
      disciplines; the mother's influence was evaluated considering her personal
      characteristics and her desire to have a thinner child. Results evidence that
      children involved in aesthetic sports, although thinner than those involved in
      non-aesthetic sports, report higher desire to be much thinner and have mothers
      who pressure them toward a greater thinness. Furthermore, children's body
      dissatisfaction in the sport groups is predicted by maternal characteristic like
      her habit to restrict her own eating and her perfectionism.

PMID- 23010782
TI  - The relationship between borderline personality symptoms and body mass index in a
      consecutive sample of cardiac stress test patients.
AB  - Borderline personality disorder (BPD) is characterized by inherent difficulties
      with self-regulation. While a number of studies have examined the relationship
      between BPD and body mass index (BMI)/overweight/obesity, findings have been
      mixed. In this cross-sectional study of a consecutive sample of 238 participants
      presenting for cardiac stress testing, we investigated the relationship between
      borderline personality symptoms, according to two self-report measures, and BMI.
      Compared to participants who were negative on both measures of borderline
      personality symptoms, participants who were positive on either measure of
      borderline personality symptoms demonstrated no differences in current BMI or
      highest BMI in adulthood. These results in a unique study population mirror the
      findings of other studies in medical and community populations.

PMID- 23010783
TI  - Attention deficit hyperactivity disorder increases the risk of having abnormal
      eating behaviours in obese adults.
AB  - OBJECTIVE: To determine the rate of abnormal eating behaviours in obese adult
      patients with attention deficit hyperactivity disorder (ADHD) in comparison with
      obese adult patients without ADHD. METHOD: This case-control study includes:
      obese adult patients defined by a body mass index (BMI) >=30 kg/m2, screening
      positive in the adult ADHD self-report scale-V1.1. (ASRS-V1.1), attending the
      Nutrition Section, as cases; and obese adult patients screening negative, as
      controls. Weight, height and BMI were determined in all the participants. The
      rate of abnormal eating behaviours was determined using an eating pattern
      questionnaire. RESULTS: Forty-five out of 51 (88.2%) cases vs 127 out of 179
      (70.9%) controls had abnormal eating behaviours (p=0.01). Eating between-meal
      snacks was found in 39 (76.5%) cases vs 107 (59.8%) controls (p=0.03), going on
      binge eating episodes in 28 (54.9%) vs 42 (23.5%) (p=0.00), waking up at night to
      eat in 11 (21.6%) vs 16 (8.9%) (p=0.01), eating large amounts of food in 13
      (25.5%) vs 38 (21.2%) (p=0.52), and eating in secret in 11 (21.6%) vs 16 (8.9%)
      (p=0.01), respectively. CONCLUSION: This is the first study that determines the
      rate of these abnormal eating behaviours in obese adult patients with ADHD in
      comparison with obese adult patients without ADHD. A high rate of abnormal eating
      behaviours was observed in obese patients with ADHD. Our results suggest that
      ADHD is a risk factor for the development of these abnormal eating behaviours,
      which may be contributing factors of obesity and the unsuccessful treatment of
      obese patients.

PMID- 23010784
TI  - Differences in laboratory eating behaviour between overweight boys and girls
      before treatment.
AB  - Sex differences in treatment response have been observed in overweight children.
      The present study therefore investigated differences in 52 boys and girls before
      treatment, with respect to laboratory eating characteristics, measured with a
      universal eating monitor. Differences were obtained for average eating rate
      (p<0.01), frequency of spoonfuls (p<0.01), and a trend for differences was seen
      for initial eating rate (p<0.10). The results point to the necessity of specific
      treatment elements for boys to modify their unfavourable microstructure of
      intake.

PMID- 23010785
TI  - Pitfalls of the psychotherapy of twins with eating disorders.
AB  - AIM: Scientific literature is limited on problems related to the psychotherapy of
      twins, especially eating disorders. This paper discusses the therapeutic
      difficulties encountered with two anorexic and one bulimic sets of twins. METHOD
      AND RESULTS: The three case reports show that the symbiotic tendency of twins is
      a frequent phenomenon, which may be a special resistance against change, and can
      serve as a factor maintaining the pathological state. In many cases, the parental
      behaviour strengthens the symbiosis of the twins, instead of helping the
      individuation. CONCLUSION: The integration of individual and family therapeutic
      interventions is proposed. The separation-individuation process of the twins can
      be stimulated by individual sessions with each of the twins, or separate sessions
      during family therapy (i.e., sessions with the parents and with one of the
      twins). In this case, the best strategy would be to have the individual and
      family therapies conducted by the same therapist.

PMID- 23010786
TI  - Visual deterioration caused by vitamin A deficiency in patients after bariatric
      surgery.
AB  - Vitamin A deficiency (VAD) after bariatric surgery is recognised as a significant
      post-operative complication that can lead to visual impairment. We report two
      cases of night blindness and visual impairment caused by VAD after malabsorptive
      bariatric surgery. Both patients were treated with intramuscular vitamin A
      replacement and made near complete recovery in their vision. Ocular complications
      due to VAD should be diagnosed and treated promptly in patients after bariatric
      surgery because these complications are reversible.

PMID- 23010787
TI  - The Attitudes and Patterns of Eating (APE) Questionnaire: development and factor
      analysis in a U.S. adolescent community sample.
AB  - OBJECTIVE: This paper describes the creation and demonstrates the internal
      consistency of the Attitudes and Patterns of Eating (APE) Questionnaire, English
      version, which assesses adolescent food beliefs and eating habits and can be used
      for comparative studies on various cultures and lifestyles. The questionnaire is
      intended for use in a study comparing French and U.S. adolescents, the details of
      which will be presented in a future article. METHOD: A research team composed of
      French and American researchers observed eating behaviors in community samples
      from each country and reviewed previous studies comparing Europe and North
      America regarding eating attitudes/practices. Common eating-related themes were
      identified and corresponding questionnaire items were constructed, then a group
      of U.S. high school students (N=1230) was administered the questionnaire.
      RESULTS: A principal components analysis (PCA) identified 5 components: "Eating
      Diet/Light Foods," "Unhealthy/Increased Eating," "Homemade Meals," "Skipping
      Meals" and "Healthy Eating". DISCUSSION: The testing and factor analysis of the
      APE (English) Questionnaire demonstrated its internal consistency. Further
      validity and reliability studies will be needed to complete the global validation
      process for both the French and English versions.

PMID- 23010788
TI  - Copper-catalyzed intramolecular direct amination of sp2 C-H bonds for the
      synthesis of N-aryl acridones.
AB  - A copper-catalyzed approach for the synthesis of N-aryl acridones via sp(2) C-H
      bond amination using air as oxidant under neutral conditions is disclosed. This
      reaction not only provides a complementary method for synthesizing medicinally
      important acridones, but also offers a new strategy for sp(2) C-H bond amination.

PMID- 23010790
TI  - Antibiotics do not reduce post-tonsillectomy morbidity in children.
AB  - The objectives are to assess the efficacy of antibiotics in reducing post
      tonsillectomy morbidities in children. This is a clinical trial study that was
      undertaken at the Jordan University Hospital during the period from June 2008 to
      July 2009. All patients undergoing tonsillectomy were randomly divided into two
      matched groups on alternating basis: group A included patients who received
      antibiotics (amoxicillin with clavulanic acid) for 5 days in the post
      tonsillectomy period and group B included patients who received none. The two
      groups were compared with respect to fever, secondary bleeding, throat pain, and
      the time to resume to normal diet. Bleeding was more common in group A (5.5 %)
      than in group B (2 %). The average duration of throat pain was 4.2 days in group
      A, while it was 3.9 days in group B. The average time to resume normal diet was
      5.7 days in group A, whereas it was 5.3 days in group B. Fever was noted in 17
      (31 %) patients from group A, while it was observed in 15 (30 %) patients from
      group B. The use of antibiotics in the post-tonsillectomy period does not reduce
      post-operative morbidity in children and therefore it is advised to use
      antibiotics on an individual basis rather than routinely for patients undergoing
      tonsillectomy.

PMID- 23010789
TI  - Impact of video-endoscopy on the results of retrosigmoid-transmeatal microsurgery
      of vestibular schwannoma: prospective study.
AB  - Endoscopy-assisted microsurgery represents modern trend of treatment of the
      cerebellopontine angle (CPA) pathologies including vestibular schwannoma (VS).
      Endoscopes are used in adjunct to microscope to achieve better functional results
      with less morbidity. Angled optics, magnification and illumination enable
      superior view in the operative field. Consecutive 89 patients with untreated
      unilateral sporadic vestibular schwannoma undergoing tumor resection via a
      retrosigmoid approach during 2008-2010 were prospectively analysed. Endoscopy
      assisted microsurgical (EA-MS) removal was performed in 39 cases (Grade 1: 2,
      Grade 2: 5, Grade 3: 9, Grade 4: 22, Grade 5: 1) and microsurgical (MS) removal
      was performed in 50 cases (Grade 1: 1, Grade 2: 3, Grade 3: 9, Grade 4: 34, Grade
      5: 3). Minimally invasive approach with craniotomy <= 2.5 cm was employed for
      small tumors (Grade 1 and 2) in the EA-MS group. Endoscopic technique was used
      for monitoring of neuro-vascular anatomy in CPA, during dissection of the meatal
      portion of tumors, assessment of radicality and for identification of potential
      pathways for CSF leak formation. All cases in MS group were deemed as radically
      removed. In the EA-MS group, residual tumor tissue in the fundus of internal
      auditory canal not observable with microscope was identified with endoscope in
      four cases. Such cases were radicalized. Tumor recurrence was not observed during
      the follow-up in EA-MS group. There is a suspicious intrameatal tumor recurrence
      on the repeated MRI scan in one patient in the MS group. Neither mortality nor
      infection was observed. The most common complication was pseudomeningocele (EA-MS
      20 cases; MS 23). It was managed with aspiration with or without tissue-gluing in
      all cases without the need for any surgical revision. Adjunctive use of endoscope
      in the EA-MS group identified potential pathways for CSF leak formation, which
      was not observable with the microscope in five patients. Improved cochlear nerve
      (EA-MS: 22, MS: 14; p = 0.012), brainstem auditory evoked potentials (EA-MS: 3 of
      8, MS: 0 of 4) and hearing (EA-MS: 14 of 36, MS: 4 of 45; p = 0.001) preservation
      were observed in EA-MS group. Despite the trend for better useful hearing
      (Gardner-Robertson class 1 and 2) preservation (EA-MS: 8 of 26, MS: 1 of 16)
      there were no significant differences in the postoperative hearing handicap
      inventory in both groups. There were no differences in the postoperative tinnitus
      in both groups. Better facial nerve preservation (EA-MS: 39, MS: 44; p = 0.027)
      and excellent-very good (House-Brackmann 1 or 2) facial nerve function (EA-MS:
      31, MS: 29; p = 0.035) were observed in EA-MS group. Postoperative compensation
      of vestibular lesion, symptoms typical for VS, patients assessed by dizziness
      handicap inventory, facial disability index were comparable in both studied
      groups. Adjunctive use of endoscope during the VS surgery due to its
      magnification and illumination enable superior view in the operative field. It is
      valuable for assessment of radicality of resection in the region of internal
      auditory meatus. Improved information about critical structures and tumor itself
      helps the surgeon to preserve facial nerve and in selected cases also hearing.
      These techniques can help to decrease incidence of postoperative complications.

PMID- 23010791
TI  - Comparison of incus interpositioning technique versus glass ionomer cement
      application in type 2 tympanoplasty.
AB  - Objective of this study is to compare glass ionomer cement application and incus
      interpositioning techniques in patients who have chronic otitis media, conductive
      hearing loss with intact tympanic membrane and who undergo hearing reconstruction
      of staged surgery using a retrospective chart review in the setting of Ministry
      of Health Ankara Training and Research Hospital ENT Clinic, Turkey. We
      retrospectively evaluated patients who underwent otological surgery and hearing
      reconstruction with auto graft incus during 2005-2008 or glass ionomer cement
      during 2008-2010. Patients who had cholesteatoma, stapes fixation and
      tympanosclerosis were excluded. Postoperative mean follow-up time of 107 patients
      was 9.8 months (6-38 months, 83.2 % of them was <= 9 months). Postoperative pure
      tone hearing thresholds, graft status, gain scores and air bone gaps were
      recorded. Intact graft, dry ear on the operated side and ABG scores less than 20
      dB were accepted as surgical success. Preoperative ABG score was 30.6 +/- 7.93 dB
      in glass ionomer (group I) and 33.6 +/- 11.99 dB in incus interpositioning (group
      II). Postoperative ABG scores were 13.6 +/- 10.40 and 22.6 +/- 12.39 dB,
      respectively, in group I and II. Success of closure in ABG scores was obtained in
      both groups (p < 0.001). Gain scores in group I were better (p = 0.035). Graft
      success (p = 0.020) correlated with gain score. Results showed that the glass
      ionomer cement application is a good, cost-effective technique, easy to perform
      and yields better hearing scores and lower complication rates compared to incus
      interpositioning technique.

PMID- 23010792
TI  - The temporary effect of short-term endotracheal intubation on vocal function.
AB  - The objective of the study was to assess and perceive the vocal and pharyngeal
      symptoms and acoustic changes of voice after short-term endotracheal intubation
      and to evaluate the relation between these changes and the endotracheal tube
      parameters, number of intubation attempts, duration of anaesthesia, experience of
      anaesthesiologist. A total of 108 patients were evaluated preoperatively, 1-2 and
      24 h after extubation. The vocal and pharyngeal symptoms, voice acoustic
      characteristics and maximum phonation time (MPT) were evaluated to find the
      relationship with endotracheal tube parameters, number of intubation attempts,
      duration of anaesthesia, experience of anaesthesiologist. All vocal and
      pharyngeal symptoms increased significantly at 24 h and remained significantly
      increased at 24 h after general anaesthesia. The vocal acoustic parameters
      changed significantly at 1-2 h: decrease of MPT and increase relative average
      perturbation were recorded. The day after the short-term intubation: only noise
      to harmony ratio and habitual pitch remains significantly changed. The most
      important endotracheal tube parameters that affect significantly (P value <0.05)
      the vocal function were the size of tube, cuff volume and number of intubation
      attempts. In relation to the anaesthesia, the changes of the acoustic parameters
      did not associate significantly with the anaesthesia-related parameters. No
      statistically significant relationship between experience of an anaesthesiologist
      and changes of the voice after anaesthesia was detected. Though being short-term,
      endotracheal anaesthesia is an invasive procedure, and its temporary influence on
      vocal function is important.

PMID- 23010793
TI  - A prognostic role for Nm23-H1 in laryngeal carcinoma treated with postoperative
      radiotherapy: an introductory investigation.
AB  - Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at
      high risk of recurrence after surgery. There are currently no clinicopathological
      parameters available to predict response to such adjuvant RT in LSCC, and only a
      few potentially predictive biomarkers have been investigated. Nm23-H1 protein is
      reportedly related to the tumor cells' metastatic potential, and low Nm23-H1
      expression levels in human carcinomas often correlate with a poor prognosis. The
      novel aim of the present preliminary study was to investigate the prognostic
      value of Nm23-H1 expression and subcellular localization in a series of patients
      given postoperative RT for LSCC. A retrospective clinicopathological
      investigation was conducted at an academic tertiary referral center of 28
      consecutive patients given postoperative RT for LSCC. Image analysis of
      immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear
      expression levels. Disease-free survival (DFS) was significantly shorter among
      LSCC patients with total Nm23-H1 levels <50.0 % (p = 0.03); the mean total Nm23
      H1 expression was lower in patients with recurrent disease than in patients
      without it (statistical trend, p = 0.07). The disease recurrence rate was
      significantly higher (p = 0.021) and the DFS shorter (statistical trend, p =
      0.052) among LSCC patients with nuclear Nm23-H1 levels <5.0 %. The locoregional
      recurrence-risk ratio in LSCC patients with nuclear Nm23-H1 levels <5.0 % was
      9.16. Nm23-H1 warrants further investigation of its potential role as a
      predictive biomarker with a view to providing tailored treatments after surgery,
      such as combinations of chemotherapy and RT instead of RT alone, in patients
      whose LSCCs have low or no Nm23-H1 expression.

PMID- 23010794
TI  - From external to internal auditory canal: surgical anatomy by an exclusive
      endoscopic approach.
AB  - Surgical approaches to the inner ear and internal auditory canal (IAC) are well
      known and well documented. The objective of this study is to analyze the
      morphology, and surgical and anatomic findings of an exclusive endoscopic
      transcanal approach (EETA) to the IAC. Cadaveric dissections were performed on 11
      temporal bones, approaching the internal auditory meatus directly through the
      external ear canal and avoiding mastoidectomy. In all cases, it was possible to
      dissect the internal carotid artery and jugular bulb with a 0 degrees  endoscope,
      and with good control of these two structures. The medial wall of the bony
      labyrinth guaranteed good landmarks for IAC dissection, such as the spherical
      recess, and the labyrinthine tract of the facial nerve. The IAC can be thoroughly
      visualized in the cadaver using EETA, avoiding mastoidectomy, extensive temporal
      bone tissue removal and external incisions. Clinically based reports will be
      required in future to strengthen our preliminary results.

PMID- 23010795
TI  - Exploring the characteristics of children with obstructive adenoid responding to
      mometasone fuorate monohydrate: preliminary results.
AB  - This study aimed at observing the efficacy of mometasone fuorate monohydrate
      nasal spray on obstructive adenoids in children and identifying the
      characteristics of responders using a pilot study including children aged 2-11
      years, with evidence of more than 50 % obstruction. Allergic rhinitis and nasal
      obstruction were evaluated on baseline (V0), 6- (V1), and 12-week (V2) visits.
      Degree of obstruction was evaluated by nasopharyngoscopy at V0 and V2. Subjects
      received 100 MUg mometasone fuorate daily. Results were compared with those of a
      matching control group. Nineteen children (8 females, 11 males; 2.25-8.50 years
      old, mean 4.24 years, median 4.00 years) completed treatment and follow-up
      adequately. There was 58 % reduction in a clinical score assessing the severity
      of adenoidal obstruction (P < 0.05), 56 % reduction in severity of obstructive
      symptom (P < 0.05), and 75 % reduction in allergic rhinitis score (P < 0.05)
      between V0 and V1. No further significant improvement was noticed between V1 and
      V2. The degree of obstruction dropped from 85 to 61 % as noted on endoscopy (P <
      0.05). None in the control group showed spontaneous decrease or resolution of the
      symptoms. Age of patients, allergic rhinitis score, and severity of the clinical
      score had no impact on the response parameters. No side effects were observed.
      Mometasone furoate monohydrate nasal spray appears to be effective in treating
      children with obstructive adenoids. The effect seems to be independent of the
      presence of mild intermittent allergic rhinitis, the age of patient, or the
      severity of symptoms.

PMID- 23010796
TI  - Comparison of three techniques in adult tonsillectomy.
AB  - This study aimed at investigating the thermal welding (TW), classic dissection
      (CD) and bipolar cautery dissection (BCD) tonsillectomy in adults. 120 adults
      with chronic tonsillitis, who were scheduled for elective tonsillectomy between
      January 2009 and April 2012, were randomized to tonsillectomy with the TW, CD and
      BCD methods. Operation time, intraoperative blood loss, post-operative
      haemorrhage rate and especially post-operative pain were evaluated. The
      difference between operative time of the TW and BCD groups against CD group was
      statistically significant (p < 0.05). The difference between intraoperative blood
      loss of the TW and BCD groups against CD group was statistically significant (p <
      0.05). No significant difference was found in the incidence of post-tonsillectomy
      haemorrhage between the three groups (p > 0.05). The difference between post
      operative pain score between CD and TW was not statistically significant (p >
      0.05). The difference between post-operative pain score of the two groups against
      BCD group was statistically significant (p < 0.05). TW technique is a relatively
      safe and reliable method with significantly less post-operative morbidity than CD
      and BCD tonsillectomy. When we compared TW with the CD and BCD tonsillectomy, we
      found significant reduction in the surgical time and the intraoperative blood
      loss without any increase in the post-operative pain.

PMID- 23010797
TI  - Altered feeding and body weight following melanocortin administration to the
      ventral tegmental area in adult rats.
AB  - RATIONALE: The melanocortin system is an important component of the brain
      circuitry controlling feeding and body weight, and most of the effects of
      melanocortins are attributed to their actions in hypothalamic and brainstem
      nuclei. The mesolimbic dopamine system is another component of the central
      circuitry controlling feeding, and there is evidence that melanocortins can act
      on mesolimbic dopamine pathways. It is unknown, however, whether melanocortins
      can act on the mesolimbic dopamine system to regulate feeding. OBJECTIVE: These
      studies tested whether injection of melanocortin receptor agonists and
      antagonists directly into the ventral tegmental area (VTA) of adult rats affects
      feeding and body weight. METHODS: Varying doses of the melanocortin receptor
      agonist, MTII, or the melanocortin receptor antagonist, SHU9119, were injected
      directly into the VTA, and food intake was measured at specific intervals. In
      addition, melanocortin receptors in the VTA were chronically blocked through
      repeated daily injections of SHU9119 into the VTA, and the resulting effects on
      food intake and body weight were determined. RESULTS: Injection of MTII into the
      VTA dose-dependently inhibited feeding for up to 24 h, while injection of SHU9119
      into the VTA dose-dependently stimulated feeding for up to 24 h. In addition,
      chronic blockade of melanocortin receptors in the VTA increased feeding, body
      weight, and caloric efficiency. CONCLUSIONS: These studies demonstrate that
      melanocortins can control feeding and body weight by acting in the VTA and
      suggest that endogenous melanocortins control feeding in part through actions on
      the mesolimbic dopamine system in vivo.

PMID- 23010799
TI  - Genetic labeling of Tas1r1 and Tas2r131 taste receptor cells in mice.
AB  - Characterization of the peripheral taste system relies on the identification and
      visualization of the different taste bud cell types. So far, genetic strategies
      to label taste receptor cells are limited to sweet, sour, and salty detecting
      cells. To visualize Tas1r1 umami and Tas2r131 bitter sensing cells, we generated
      animals in which the Tas1r1 and Tas2r131 open reading frames are replaced by
      expression cassettes containing the fluorescent proteins mCherry or hrGFP,
      respectively. These animals enabled us to visualize and quantify the entire oral
      Tas1r1 and Tas2r131 cell populations. Tas1r1-mCherry cells were predominantly
      detected in fungiform papillae, whereas Tas2r131-hrGFP cells, which are ~4-fold
      more abundant, were mainly present in foliate and vallate papillae. In the
      palate, both cell types were similarly distributed. Mice carrying both
      recombinant alleles demonstrated completely segregated Tas1r1 and Tas2r131 cell
      populations. Only ~50% of the entire bitter cell population expressed hrGFP,
      indicating that bitter taste receptor cells express a subset of the bitter
      receptor repertoire. In extragustatory tissues, mCherry fluorescence was observed
      in testis and hrGFP fluorescence in testis, thymus, vomeronasal organ, and
      respiratory epithelium, suggesting that only few extraoral sites express Tas2r131
      and Tas1r1 receptors at levels comparable to taste tissue.

PMID- 23010798
TI  - Exaggerated cue-induced reinstatement of cocaine seeking but not incubation of
      cocaine craving in a developmental rat model of schizophrenia.
AB  - RATIONALE: Patients with schizophrenia exhibit high comorbidity for substance
      abuse, but the biological underpinnings of this dual-diagnosis condition are
      still unclear. Previous studies have shown that rats with a neonatal ventral
      hippocampal lesion (NVHL), a widely used developmental animal model of
      schizophrenia, exhibit increased cocaine and methamphetamine self-administration
      and cocaine-induced reinstatement. OBJECTIVE: Here, we assessed whether a NVHL
      would also potentiate cue-induced reinstatement of cocaine seeking and the time
      dependent increases in cue-induced cocaine seeking after withdrawal (incubation
      of cocaine craving) in adult rats. METHODS: Rats were trained to self-administer
      cocaine (3 or 6 h/day with 0.75 mg kg(-1) infusion(-1) paired with a tone-light
      cue) for 10 days, followed by extinction training (3 h/day) and cue-induced
      reinstatement of cocaine seeking. Other rats were tested for incubation of
      cocaine craving, assessed in extinction tests 1 and 30 days after the last self
      administration session. RESULTS: Although there was no significant difference in
      cocaine intake between NVHL and sham controls, NVHL rats took significantly
      longer to reach an a priori set extinction criterion and exhibited enhanced cue
      induced reinstatement. However, while cue-induced cocaine seeking was higher
      after 30 days than after 1 day of withdrawal (incubation of cocaine craving), the
      NVHL had no effect on this incubation. CONCLUSION: These data confirm previous
      reports on enhanced resistance to extinction after NVHL and demonstrate that NVHL
      rats exhibit enhanced cue-induced reinstatement of cocaine seeking after
      extinction, a measure of drug relapse.

PMID- 23010800
TI  - Perioperative outcomes of revisional laparoscopic gastric bypass after failed
      adjustable gastric banding and after vertical banded gastroplasty: experience
      with 107 cases and subgroup analysis.
AB  - BACKGROUND: A growing number of revision procedures are to be expected in
      bariatric surgery after failed restrictive procedures such as failed adjustable
      gastric banding (AGB) or vertical banded gastroplasty (VBG). Conversion to
      revisional laparoscopic Roux-en-Y gastric bypass (ReLRYGBP) has been advocated as
      the procedure of choice. METHODS: The results of ReLRYGBP were reviewed in a
      retrospective chart review. A subgroup analysis compared perioperative results
      after VBG and after AGB. A second subgroup analysis compared perioperative
      results of ReLRYGBP immediately after AGB removal and after a delay as a two-step
      procedure. RESULTS: Between 2003 and 2009, ReLRYGBP was performed for 107
      patients. Of these 107 operations, 21 were performed after failed VBG and 86
      after failed AGB. The mean body mass index (BMI) was 42 kg/m(2). The causes of
      failure were mainly insufficient weight loss or reflux disease-related symptoms.
      During a median follow-up period of 44 months, there was no mortality, and
      morbidity was 34 %, including late complications. Major early complications
      occurred in 11 % of the cases (n = 12). Conversions and major early complications
      occurred significantly more frequently after VBG than after AGB (p < 0.05). In 59
      % of the cases (n = 50), ReLRYGBP was performed as a single-stage procedure
      immediately after removal of AGB and in 41 % of the cases (n = 36) as a delayed
      two-step procedure. The outcomes did not differ significantly (p > 0.5).
      CONCLUSIONS: The perioperative outcomes of ReLRYGBP are worse after VBG than
      after AGB. The ReLRYGBP operation can be performed safely as a one-step procedure
      after AGB removal.

PMID- 23010801
TI  - Synthesis and immunochemical evaluation of a non-methylated disaccharide analogue
      of the anthrax tetrasaccharide.
AB  - Anthrax tetrasaccharide is an oligosaccharide expressed at the outermost surface
      of the Bacillus anthracis spores, featuring three rhamnoses and a rare sugar
      called anthrose. This motif has now been identified as a plausible component of
      future human vaccines against anthrax. We report herein the synthesis of a 2-O
      demethylated-beta-D-anthropyranosyl-(1->3)-alpha-L-rhamnopyranose disaccharide
      analogue of this tetrasaccharide from a cyclic sulfate intermediate. This
      disaccharide conjugated to BSA induces an anti-native tetrasaccharide IgG
      antibody response when administered in BALB/c mice. Moreover, induced sera bound
      to native B. anthracis endospores. These results suggest that the disaccharide
      analogue, easily amenable for a synthetic scale-up, could be used in a
      glycoconjugate antigen formulation.

PMID- 23010802
TI  - Activating CBL mutations are associated with a distinct MDS/MPN phenotype.
AB  - Activating point mutations in CBL have recently been identified in diverse
      subtypes of myeloid neoplasms. Because detailed clinical and hematological
      characteristics of CBL-mutated cases is lacking, we screened 156 BCR-ABL and JAK2
      V617F negative patients with myeloproliferative neoplasms (MPN) and overlap
      syndromes between myelodysplastic syndrome (MDS) and MPN (MPS/MPN) for mutations
      in exons 8 and 9 of CBL by denaturing high-performance liquid chromatography and
      direct sequencing. CBL mutations were identified in 16/156 patients (10%), of
      which five also carried mutations in EZH2 (n = 3) and TET2 (n = 2). Comprehensive
      clinical and hematological characteristics were available from 13/16 patients
      (81%). In addition to splenomegaly (77%), striking common hematological features
      were CML-like left-shifted leukocytosis (85%) with monocytosis (85%), anemia
      (100%), and thrombocytopenia (62%). Thrombocytosis was not observed in any
      patient. Relevant bone marrow features (n = 12) included hypercellularity (92%)
      with marked granulopoiesis (92%), nonclustered microlobulated megakaryocytes
      (83%), and marrow fibrosis (83%). Nine deaths (progression to secondary acute
      myeloid leukemia/blast phase, n = 7; cytopenia complications, n = 2) were
      recorded. Three-year survival rate was 27%, possibly indicating poor prognosis of
      CBL mutated MDS/MPN patients.

PMID- 23010804
TI  - Dalton Discussion 13: Inorganic photophysics and photochemistry: fundamentals and
      applications (DD13).

PMID- 23010803
TI  - Perioperative brain shift and deep brain stimulating electrode deformation
      analysis: implications for rigid and non-rigid devices.
AB  - Deep brain stimulation (DBS) efficacy is related to optimal electrode placement.
      Several authors have quantified brain shift related to surgical targeting; yet,
      few reports document and discuss the effects of brain shift after insertion.
      OBJECTIVE: To quantify brain shift and electrode displacement after device
      insertion. Twelve patients were retrospectively reviewed, and one post-operative
      MRI and one time-delayed CT were obtained for each patient and their implanted
      electrodes modeled in 3D. Two competing methods were employed to measure the
      electrode tip location and deviation from the prototypical linear implant after
      the resolution of acute surgical changes, such as brain shift and pneumocephalus.
      In the interim between surgery and a pneumocephalus free postoperative scan,
      electrode deviation was documented in all patients and all electrodes.
      Significant shift of the electrode tip was identified in rostral, anterior, and
      medial directions (p < 0.05). Shift was greatest in the rostral direction,
      measuring an average of 1.41 mm. Brain shift and subsequent electrode
      displacement occurs in patients after DBS surgery with the reversal of
      intraoperative brain shift. Rostral displacement is on the order of the height of
      one DBS contact. Further investigation into the time course of intraoperative
      brain shift and its potential effects on procedures performed with rigid and non
      rigid devices in supine and semi-sitting surgical positions is needed.

PMID- 23010805
TI  - Cellular imaging using biocompatible dendrimer-functionalized graphene oxide
      based fluorescent probe anchored with magnetic nanoparticles.
AB  - We describe a novel multicomponent graphene nanostructured system that is
      biocompatible, and has strong NIR optical absorbance and superparamagnetic
      properties. The fabrication of the multicomponent nanostructure system involves
      the covalent attachment of 3 components; Fe(3)O(4)(Fe) nanoparticles, PAMAM-G4
      NH(2) (G4) dendrimer and Cy5 (Cy) on a graphene oxide (GO) surface to synthesize
      a biologically relevant multifunctional system. The resultant GO-G4-Fe-Cy
      nanosystem exhibits high dispersion in an aqueous medium, and is magnetically
      responsive and fluorescent. In vitro experiments provide a clear indication of
      successful uptake of the GO-G4-Fe-Cy nanosystem by MCF-7 breast cancer cells, and
      it is seen to behave as a bright and stable fluorescent marker. The study also
      reveals varied cellular distribution kinetics profile for the GO nanostructured
      system compared to free Cy. Furthermore, the newly developed GO nanostructured
      system is observed to be non-toxic to MDA-MB-231 cell growth, in striking
      contrast to free G4 dendrimer and GO-G4 conjugate. The GO-G4-Fe-Cy nanostructured
      system characterized by multifunctionality suggests the merits of graphene for
      cellular bioimaging and the delivery of bioactives.

PMID- 23010808
TI  - Breastfeeding: preserving a human instinct.

PMID- 23010807
TI  - Applying competing risks regression models: an overview.
AB  - In many clinical research applications the time to occurrence of one event of
      interest, that may be obscured by another--so called competing--event, is
      investigated. Specific interventions can only have an effect on the endpoint they
      address or research questions might focus on risk factors for a certain outcome.
      Different approaches for the analysis of time-to-event data in the presence of
      competing risks were introduced in the last decades including some new
      methodologies, which are not yet frequently used in the analysis of competing
      risks data. Cause-specific hazard regression, subdistribution hazard regression,
      mixture models, vertical modelling and the analysis of time-to-event data based
      on pseudo-observations are described in this article and are applied to a dataset
      of a cohort study intended to establish risk stratification for cardiac death
      after myocardial infarction. Data analysts are encouraged to use the appropriate
      methods for their specific research questions by comparing different regression
      approaches in the competing risks setting regarding assumptions, methodology and
      interpretation of the results. Notes on application of the mentioned methods
      using the statistical software R are presented and extensions to the presented
      standard methods proposed in statistical literature are mentioned.

PMID- 23010809
TI  - Smoking and nicotine dependence in Singapore: findings from a cross-sectional
      epidemiological study.
AB  - INTRODUCTION: Smoking is one of the leading preventable causes of death
      throughout the world and can lead to nicotine dependence, particularly when
      initiated at a young age. This paper describes the prevalence of smoking and
      nicotine dependence in the adult Singapore resident population, whilst also
      exploring rates among the major ethnic groups (Chinese, Malay and Indian),
      different education levels and those with chronic psychiatric and physical
      comorbidities. MATERIAL AND METHODS: The Singapore Mental Health Study (SMHS) is
      a cross-sectional epidemiological study that was conducted between December 2009
      and December 2010. Information on smoking status was assessed using the Composite
      International Diagnostic Interview version 3.0 (CIDI 3.0) and the Fagerstrom Test
      for Nicotine Dependence measured nicotine dependence. Socio-demographic
      information was also collected. RESULTS: In total, 6616 respondents participated
      in the SMHS giving a response rate of 75.9%. We found that 16% of the population
      were current smokers and 4.5% had nicotine dependence. Current smokers were more
      likely to be younger (18 to 34 years old), males, Malay and have lower education,
      whilst males had a 4.6 times higher risk of nicotine dependence to that of
      females. The prevalence of nicotine dependence was also higher in those with
      alcohol abuse and those experiencing chronic pain. CONCLUSION: The results from
      this study highlight the important differences in the prevalence of smoking and
      nicotine dependence among different age groups, gender and ethnicity in Singapore
      and are important for developing future health policies and targeted preventive
      strategies.

PMID- 23010810
TI  - Unused arteriovenous grafts as a source of chronic infection in haemodialysed
      patients with relevance to diagnosis of Fluorodeoxyglucose PET/CT examination.
AB  - INTRODUCTION: Clotted arteriovenous grafts (AVG) for haemodialysis which are not
      used (silent grafts) can serve as a potential source of chronic bacterial
      infection in patients on dialysis programs. In some cases, the local finding is
      unclear. The patient only suffers from repeated metastatic infection and the
      detection of AVG infection is difficult. Nuclear medicine methods have the
      potential to uncover AVG infection. In this study, we correlated the positron
      emission tomography (PET)/ computed tomography (CT) findings of the AVG
      examination with the microbiological findings from removed grafts. The aim was to
      evaluate the relevance of the Fluorodeoxyglucose (FDG) PET/CT method in detecting
      clotted graft infection. MATERIAL AND METHODS: A cohort of 13 patients with
      clotted grafts were followed-up. Four patients had overall symptoms of infection
      and 9 patients were asymptomatic. In all cases, the PET CT examination and
      microbiological examination of the removed graft were provided. RESULTS: Only one
      mismatch-negative PET CT finding and positive microbiological culture was
      recorded in the 13 followed-up patients. CONCLUSION: In patients with silent
      grafts and recurrent infection of equivocal aetiology, PET CT examination can
      contribute to the diagnosis of AVG infection and, subsequently, to prevent
      further infectious complications, if the AVG infection is treated appropriately
      and the graft is removed.

PMID- 23010811
TI  - National Health Survey on the prevalence of urinary abnormalities in the
      population: then and now (1975 to 2012).
AB  - INTRODUCTION: This paper presents the results of a community survey on urinary
      abnormalities which covered 1/80th of the population of Singapore in 1975. These
      findings were compared with the data from the Singapore National Service
      Registrants in 1974 as well as data from a recent survey in Singapore and that of
      other Asian and Western countries. MATERIALS AND METHODS: The study covered
      18,000 persons aged 15 years and above, representing a sampling fraction of
      1/80th of the population. A total of 16,808 respondents attended the field
      examination centres, of whom 16,497 had their urine sample tested representing
      92.7% of the sample population. RESULTS: In the dipstick urine testing at the
      field examination centres, 769 subjects (4.6%) were found to have urinary
      abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were
      found to have urinary abnormalities based on urine microscopy constituting a
      prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both
      haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43%
      and renal insufficiency was 0.1%. DISCUSSION: The consensus is that routine
      screening for chronic kidney disease (CKD) in the general population is not cost
      effective as the yield is too low. Whilst, most studies showed that screening of
      the general population was not cost effective, it has been suggested that
      screening for targeted groups of subjects could help to identify certain risk
      groups who may benefit from early intervention to prevent or retard the
      progression of CKD. CONCLUSION: The prevalence of urinary abnormalities in
      Singapore has remained the same, now and three decades ago.

PMID- 23010812
TI  - Prospective evaluation of argon gas probe delivery for cryotherapy of bone
      tumours.
AB  - INTRODUCTION: Cryosurgery for tumoural ablation traditionally involves instilling
      liquid nitrogen into a tumoural bed. The inability to control precise delivery
      can result in potentially disastrous consequences of skin necrosis and nitrogen
      gas embolism. In this study, we evaluated a probe-based closed cryosurgical
      system, which eliminates these risks. MATERIALS AND METHODS: We performed a
      prospective evaluation of 36 cases of bone tumours treated with a probe-based
      cryosurgical system at the National University Hospital, Singapore. Cases
      consisted of patients with benign aggressive tumours (42%), primary malignant
      bone tumours (25%) and bone metastases (33%). In primary bone tumours, the aim of
      therapy was cure. In bone metastasis, the aim of therapy was palliation defined
      as the relief of symptoms for the patients' remaining lifetime. RESULTS: In the
      primary bone tumour group, no recurrences were reported. In the metastases group,
      where the intention was palliation, there were 3 cases of radiological relapses
      (P = 0.02) and 2 clinical relapses. Kaplan-Meier evaluation showed a
      statistically significant tendency for radiological relapse in metastatic disease
      versus primary disease (P = 0.02). Median time for relapse free survival in the
      metastatic group was 17 months (P = 0.01). There were 4 deaths in the metastatic
      group due to progression of disease unrelated to the index region of cryosurgical
      treatment. There were no deaths in the primary bone tumor group. We had 2
      complications from this therapy involving fractures through the cryoablated
      segments. One case healed spontaneously and the other was most expediently
      managed with a shoulder hemiarthoplasty. There were no skin burns or embolic
      complications. CONCLUSION: Good clinical efficacy with probe delivered
      cryotherapy has been shown in this group of 32 patients with cure in all primary
      disease. Relapse occurred in only a small proportion of patients with bone
      metastasis.

PMID- 23010813
TI  - A subacute model of geriatric care for frail older persons: the Tan Tock Seng
      Hospital experience.
AB  - INTRODUCTION: The subacute care unit in Tan Tock Seng Hospital (TTSH) was set up
      in May 2009. We examined its impact on the transitions at the nexus between
      hospital and community sectors, patients' discharge destination and functional
      performance. MATERIALS AND METHODS: We studied patients admitted during the
      initial 6-month period (May to October 2009). Differences in demographics, length
      of stay (LOS), comorbidity and severity of illness measures, functional outcomes
      (modified Barthel Index (MBI)) according to discharge destinations were obtained.
      We also studied the impact of LOS on the geriatric department and the bill size
      over the pre- and post-subacute implementation periods. RESULTS: Majority of the
      subacute patients' hospital stay was in subacute care. Of these patients, 44.9%
      were discharged home, 24.2% to a slow stream rehabilitation (SSR) setting and
      29.2% to nursing homes. 16.9% consisted of a subgroup of dementia patients
      requiring further behavioural and functional interventions, of which 50% managed
      to be discharged home. Functional gains were seen during subacute stay; with
      greatest gains observed in the SSR group. There were no differences in overall
      LOS nor total bill size (DRG-adjusted) for the geriatric medicine department
      during the first 6 months of operating this new subacute model compared with the
      prior 4-month period. CONCLUSION: We propose this subacute model of geriatric
      care, which allows right-siting of care and improved functional outcomes. It
      fulfills the role easing transitions between acute hospital and community
      sectors. In particular, it provides specialised care to a subgroup of dementia
      patients with challenging behaviours and is fiscally sound from the wider
      hospital perspective.

PMID- 23010814
TI  - Urinary bladder paraganglioma in a post-heart transplant patient.

PMID- 23010815
TI  - A persistent red eye and diplopia--when to neuroimage?

PMID- 23010816
TI  - A less known dermatological emergency.

PMID- 23010817
TI  - 7th Tan Tock Seng Oration: surgical excellence at TTSH--100 years on and onward.

PMID- 23010819
TI  - Electrochemical and electrocatalytic properties of thin films of poly(3,4
      ethylenedioxythiophene) grown on basal plane platinum electrodes.
AB  - The first part of this communication studies the electrochemical properties of
      thin films of poly(3,4-ethylenedioxythiophene) (PEDOT) grown on the three basal
      plane platinum electrodes via cyclic voltammetry, chronoamperometry,
      electrochemical impedance spectroscopy and in situ FTIR spectroelectrochemistry.
      In the second part of this work the redox reaction of 2,5-dimercapto-1,3,4
      thiadiazole (DMcT) at these platinum modified electrodes is investigated via
      cyclic voltammetry and electrochemical impedance spectroscopy in order to
      elucidate the effect of some polymer properties on its electrocatalytic behavior,
      such as the ionic resistance, nature of the doping ion and the structure. First
      of all, it was found that the ionic resistance of the PEDOT films
      electrochemically synthesized on platinum electrodes increases in the order
      Pt(100) < Pt(110) < Pt(111) and the advantages of using single crystal platinum
      electrodes coated with PEDOT for the IR study of individual mobile species flux
      and the evolution of charge carriers during the reduction process of p-doped
      PEDOT were proven. On the other hand, it was found that compact, rigid and low
      resistance PEDOT films show higher standard charge transfer rates for the DMcT
      redox reaction than those that have a more porous structure and higher ionic
      resistance. Finally, PEDOT films doped with alkaline ions are more
      electrocatalytic for the oxidation process of the protonated form of DMcT.

PMID- 23010818
TI  - Polysaccharide from Ganoderma atrum induces tumor necrosis factor-alpha secretion
      via phosphoinositide 3-kinase/Akt, mitogen-activated protein kinase and nuclear
      factor-kappaB signaling pathways in RAW264.7 cells.
AB  - The aim of this study was to investigate the signaling pathways involved in the
      macrophage activation by Ganoderma atrum polysaccharide (PSG-1) and elucidate the
      molecular mechanism of PSG-1-induced signal transduction in the regulation of
      tumor necrosis factor (TNF)-alpha secretion. Our results illustrated that the
      mitogen-activated protein kinase (MAPK) pathways were simultaneously activated
      and involved in PSG-1-induced TNF-alpha secretion in RAW264.7 cells. Moreover,
      our results also demonstrated that the phosphoinositide 3-kinase (PI3K)/Akt
      pathway was stimulated and played an important role in the PSG-1 induced TNF
      alpha secretion. Additionally, the present study showed that nuclear factor (NF)
      kappaB activation by PSG-1 was triggered by PI3K/Akt/MAPK pathway and NF-kappaB
      participated in PSG-1 stimulated TNF-alpha production. In conclusion, we have
      elucidated the mechanism of PSG-1-mediated immunomodulatory activities, and
      provide a theoretical basis for the potential of PSG-1 as a novel
      immunomodulating agent.

PMID- 23010821
TI  - Periodic acid Schiff loops and blood lakes associated with metastasis in
      cutaneous melanoma.
AB  - Aggressive melanoma cells are able to form alternative routes for angiogenesis.
      The formation of extracellular matrix-rich vasculogenic-like networks [periodic
      acid Schiff (PAS) loops] and expression of endothelial-associated genes [allowing
      direct contact of erythrocytes (blood lakes)] are forms of vasculogenic mimicry
      (VM). The detection of these alternative routes may be used as an additional
      staging factor for cutaneous melanoma and predicts the route of metastasis in
      melanoma. We studied the association of the presence of VM with metastasis
      (lymphogenous and/or haematogenous) in patients diagnosed with cutaneous
      malignant melanoma in het Groene Hart Hospital, the Netherlands, between 1995 and
      2000. Tumour tissue samples of 123 patients were assessed on PAS loops and blood
      lakes and correlated to clinical data. VM was detected in 42 (34%) and proven
      metastasis developed in 23 patients (18.7%). VM was associated with shorter
      survival (P<0.001). In 36 tumours, PAS loops were detected. PAS loops were
      correlated with the presence of lymphogenous as well as haematogenous metastasis
      (P=0.062 and 0.013). In 20 tumours, blood lakes were detected and correlated with
      haematogenous metastasis (P<0.001). In multivariate analyses, the detected blood
      lakes were significantly associated with haematogenous metastasis (P<0.001,
      adjusted odds ratio 6.8, 95% confidence interval 1.47-31). Blood lakes were
      strongly correlated with haematogenous metastasis of cutaneous melanoma and were
      an independent determinant for survival. These interesting findings need further
      investigation, although we believe that implementation of this detection can
      directly lead to better staging of cutaneous melanoma.

PMID- 23010820
TI  - Paternal transmission of mitochondrial DNA as an integral part of mitochondrial
      inheritance in metapopulations of Drosophila simulans.
AB  - Maternal inheritance is one of the hallmarks of animal mitochondrial DNA (mtDNA)
      and central to its success as a molecular marker. This mode of inheritance and
      subsequent lack of heterologous recombination allows us to retrace evolutionary
      relationships unambiguously down the matriline and without the confounding
      effects of recombinant genetic information. Accumulating evidence of biparental
      inheritance of mtDNA (paternal leakage), however, challenges our current
      understanding of how this molecule is inherited. Here, using Drosophila simulans
      collected from an East African metapopulation exhibiting recurring mitochondrial
      heteroplasmy, we conducted single fly matings and screened F1 offspring for the
      presence of paternal mtDNA using allele-specific PCR assays (AS-PCR). In all, 27
      out of 4092 offspring were identified as harboring paternal mtDNA, suggesting a
      frequency of 0.66% paternal leakage in this species. Our findings strongly
      suggest that recurring mtDNA heteroplasmy as observed in natural populations of
      Drosophila simulans is most likely caused by repeated paternal leakage. Our
      findings further suggest that this phenomenon to potentially be an integral part
      of mtDNA inheritance in these populations and consequently of significance for
      mtDNA as a molecular marker.

PMID- 23010822
TI  - Superficial-spreading and nodular melanomas in Norway:  a comparison by body site
      distribution and latitude gradients.
AB  - Superficial-spreading melanoma (SSM) and nodular melanoma (NM) are the most
      common histological types of melanoma. These are seemingly distinct entities, on
      the basis of epidemiology, clinical behavior, tumor biological, and histological
      aspects as well as molecular characteristics. Intermittent sun exposure seems to
      play a major role in SSM, which has an increasing incidence rate during the last
      decades. However, relationship with sun exposure is more complex in the case of
      NM, as the latter may arise on any body part and has a more stable incidence
      rate. To obtain more information on the role of sun exposure in these two types
      of melanoma, we have compared body site distributions and latitude gradients for
      a period of 30 years in Norway. The study was based on official reports from the
      Cancer Registry of Norway, using melanoma incidence rates for a period of 30
      years (1978-2007), by age, sex, anatomic site, and region of Norway. Our results
      show that in Norway, SSM is more strongly related to intermittent sun exposure
      than NM, as it arises mostly on the trunk as compared with the head and neck.
      Moreover, SSM has a higher incidence in the Southern regions of Norway, whereas
      for NM, the north-south gradient is not statistically significant. Differences in
      sun exposure at northern latitudes have a major impact on different types of
      melanoma. It seems that NM is less sun-induced than SSM, for which other
      etiological and pathogenetic factors may play important roles.

PMID- 23010824
TI  - Contact alternatives and the internet.
AB  - The Internet has dramatically changed the way we live our lives and the way we
      practice medicine over the past 20 years. The amount of information that is
      available, the speed at which new information is shared and disseminated, and the
      availability of that information to anyone, anywhere have all grown
      exponentially. This rapid growth presents 2 major challenges: (1) among the vast
      amount of information available, one must be able to find the specific
      information needed, at the moment it is needed, without knowing for certain if it
      even exists; (2) the accuracy and "currentness" of the information must be
      assessed once it is found.

PMID- 23010826
TI  - Cobalt sensitization and dermatitis:  considerations for the clinician.
AB  - This clinical review article presents clinical and scientific data on cobalt
      sensitization and dermatitis. It is concluded that cobalt despite being a strong
      sensitizer and a prevalent contact allergen to come up on patch testing should be
      regarded as a very complex metal to test with. Exposure data together with
      clinical data from metal workers heavily exposed to cobalt suggest that patch
      test reactions are sometimes false positive and that patch testers should
      carefully evaluate their clinical relevance.

PMID- 23010825
TI  - T-cell inhibitors: a bench-to-bedside review.
AB  - Allergic contact dermatitis is the quintessential example of a delayed-in-time
      and T-cell-mediated immune response. In the last decade, many of the molecular
      events required to initiate (or block) such a response have been uncovered.
      Textbook and journal reviews have emphasized the costimulatory requirements, with
      less focus on the coinhibitory signals that are of equal importance in
      understanding this central event of adaptive immunity. To fill this gap, we offer
      a compendium of discoveries characterizing the ligand-receptor pairs inhibiting T
      cell activation and of selected illnesses and therapeutic applications that
      illuminate their role in health and disease.

PMID- 23010828
TI  - Additive value of patch testing custom epoxy materials from the workplace at the
      occupational disease specialty clinic in Toronto.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) to epoxy resins is one of the major
      causes of occupationally induced ACD. Testing of custom epoxy materials from the
      workplace is often performed to diagnose ACD. OBJECTIVE: The objective of this
      study was to investigate the additive value of patch testing custom-made epoxy
      materials. METHOD: We retrospectively analyzed outcomes of 24 patients who were
      tested to custom epoxy resin materials between January 2002 and July 2011.
      RESULTS: For 11 patients (46%), the testing of their materials from work had no
      additional value (negative results). For 13 patients (54%), there was an
      additional value of testing custom allergens. Of those, 7 patients (54%) had
      positive reactions to custom epoxy materials that reinforced the test results
      found with the commercially available allergens, and 6 (46%) patients had
      positive reactions only to custom epoxy materials. Therefore, for 6 patients
      (25%), there was a definite additive value of testing custom epoxy materials
      because the allergy was discovered with custom testing and not with the
      commercially available allergens. CONCLUSIONS: Because of the high percentage
      (54%) of patients with additive value of patch testing custom epoxy materials, we
      think that the inclusion of actual workplace epoxy materials should be strongly
      considered when patch testing patients with occupational epoxy exposure.

PMID- 23010827
TI  - Contact dermatitis to topical medicaments: a retrospective chart review from the
      Ottawa Hospital Patch Test Clinic.
AB  - BACKGROUND: Topical medicaments are a common cause of allergic contact
      dermatitis. This study will evaluate the prevalence of contact allergy to a wide
      array of topical medicaments at the Ottawa Patch Test Clinic. OBJECTIVES: The
      objectives of this study are to report the results of positive patch testing to
      topical medicaments at the Ottawa Patch Test Clinic and identify common
      sensitizers in topical medicaments. METHODS: Patients were tested with the
      standard North American Contact Dermatitis screening series of 70 allergens plus
      supplementary allergens when indicated. A retrospective chart review of patients
      positive to topical medicaments between January 1, 2000, and September 30, 2010,
      was undertaken. RESULTS: The average age of patients was 49.5 years. Thirty-four
      percent were atopic. Common sensitizers included topical antibiotics (58%),
      steroids (30%), anesthetics (6%), and antifungals (6%). Patch testing showed that
      61% of patients tested positive to antibiotics, 21% to topical steroids, 17%
      tested positive to topical anesthetics, and 1% tested positive to topical
      antifungals. The most common reactions were to bacitracin (44%) and neomycin
      (29%). The most common steroid screener was tixocortol-17-pivalate (group A)
      (19%), and the most common local anesthetic was lidocaine (12%). CONCLUSIONS:
      Topical medicaments of all kinds are common causes of allergic contact
      dermatitis. Those that are more readily available, in over-the-counter
      preparations, are the most frequent culprits.

PMID- 23010829
TI  - Cutaneous hypersensitivity to gluten.
AB  - We enrolled 14 female patients (aged 12-60 years) affected by celiac disease
      (confirmed by duodenal biopsy), presenting dermatologic eczematous lesions
      involving their face, neck, and overall arms, after application of gluten
      containing emollient cream, bath, or face powder, or after contact with foods
      containing wheat and durum wheat. Five patients resulted positive to patch-by
      patch with wheat and durum wheat (mild to moderate positivity) with erythema and
      vesicles, in correspondence of their sites of application. Utilizing gluten-free
      cream and bath, and wearing gloves before hand contact with food-containing
      wheat, in their common life, these patients showed an improvement of their
      cutaneous lesions and no relapses of dermatitis for a 6-month follow-up period.

PMID- 23010830
TI  - Dental allergic contact dermatitis:  an interesting case series and review of the
      literature.
AB  - When patients have persistent oral complaints, it is important to consider
      allergic contact dermatitis to dental components. We present 3 cases seen at the
      Ottawa Hospital Patch Test Clinic between 2007 and 2009 with persistent oral
      lesions. Mercury, methacrylate, and beryllium were found to be the responsible
      allergens after patch testing. Of note, our case is the fourth reported dental
      contact dermatitis case to beryllium. Subsequently, a literature review and an
      examination of reported cases and management strategies were done. There is
      debate over the necessity of changing dental work after a positive patch-test
      result. We conclude that it is necessary to do your best to uncover all of the
      materials used in dental work. Often, material safety sheets do not include all
      allergens present in products. We advocate that if a positive reaction is found
      and deemed relevant, then appropriate replacement of the offending agent should
      be recommended.

PMID- 23010831
TI  - Airborne allergic contact dermatitis from tylosin in pharmacy compounders and
      cross-sensitization to macrolide antibiotics.
AB  - Tylosin is a broad-spectrum macrolide antibiotic that is restricted to veterinary
      use. Allergic contact dermatitis (ACD) caused by tylosin has been reported in the
      literature from the farming industry and veterinary medicine. It is also reported
      as the most common antibiotic to cause ACD in the previously mentioned
      occupational settings. We present 2 cases of airborne ACD from tylosin among
      veterinary pharmaceutical compounding technicians. To our knowledge, only one
      other case of patch test-confirmed tylosin ACD has been reported in the
      manufacturing setting. Based on our results, cross-sensitization to other
      clinically relevant macrolides does not appear to be a concern. Our cases
      highlight the importance of patch testing among pharmaceutical compounders where
      the incidence of an airborne contact may be greater, given that the exposure is
      to the powdered form of potential allergens.

PMID- 23010832
TI  - Hydrofluoric acid exposure: a case report and review on the clinical presentation
      and management.
AB  - Exposure to hydrofluoric acid can cause severe skin damage via both corrosive and
      chemical means. Dermatologists should be aware of the various clinical
      presentations and knowledgeable of how to manage such patients. A case of a man
      with exposure of the hands after use of a consumer product containing
      hydrofluoric acid is presented. The presentation may vary depending on the
      concentration and duration of exposure. Patients experiencing exposure are at
      risk of serious complications, including death, resulting from electrolyte
      abnormalities. Information regarding the source of exposure will allow the
      physician to better predict the patient's course. The use of immediate flushing
      with water and the use of topical calcium gluconate can prevent extensive damage
      to the area of exposure and potentially fatal complications that may occur. More
      extensive burns may necessitate more invasive therapies. The treatment and the
      management and monitoring of such cases will allow for more optimal outcomes.

PMID- 23010833
TI  - Trichomegaly of the eyelashes during therapy with epidermal growth factor
      receptor inhibitors:  report of 3 cases.
AB  - A wide spectrum of skin toxicities has been described in patients receiving
      epidermal growth factor receptor (EGFR), inhibitors, including papulopustular
      rash, xerosis and fissures, pruritus, mucositis, paronychia, and hair
      changes.Trichomegaly of the eyelashes is a rare adverse effect of EGFR inhibitor
      therapy and is characterized by a paradoxical overgrowth of eyelashes. We present
      3 cases of trichomegaly occurred during EGFR inhibitor therapy.

PMID- 23010834
TI  - Black salve as self-treatment for cutaneous squamous cell carcinoma.

PMID- 23010835
TI  - Eczema herpeticum complicating topical 5-Fluorouracil therapy.

PMID- 23010836
TI  - Long-lasting allergic patch test reaction to methyl methacrylate.

PMID- 23010837
TI  - Sodium dehydroacetate:  an emerging allergen.

PMID- 23010838
TI  - A bum deal from wooden toilet seats:  reemergence of allergic contact dermatitis.

PMID- 23010839
TI  - Cigarette smoking modulates medication-associated deficits in a monetary reward
      task in patients with schizophrenia.
AB  - Imaging studies of reward processing have demonstrated a mesolimbic-mesocortical
      dopaminergic dysfunction in schizophrenia. Such studies on reward processing in
      patients and also in healthy controls showed that differential activations of
      dopaminergic brain areas are associated with adaptive changes in response speed
      related to different reward values. Given this relationship, we investigated
      reward processing on the behavioural level in a larger sample of 49 medicated
      patients with a diagnosis of schizophrenia (ICD-10 F20) and 49 healthy controls.
      Subjects were instructed to react by button press upon two different stimuli in
      order to retain a 60 % chance winning a previously announced high (1$) or low
      (20c) amount of money paid to participants after the experiment. Concordant with
      previous reports on deficits in reward processing, acceleration of reaction times
      in patients upon low rewards differed significantly (p < 0.05) from healthy
      controls in our present behavioural study. This effect was pronounced in the non
      smoking subgroup of patients (n = 24). In this subgroup, we also observed a
      significant (p < 0.05) positive correlation with medication type (relatively high
      vs. low D2 receptor affinity) and with the PANSS score, the latter with a trend
      to significance (p = 0.08). Our study demonstrates that reaction time measures in
      a monetary reward task might constitute a feasible behavioural proxy for
      dopaminergic dysfunction and its different dimensions regarding psychopathology
      but also medication in patients with schizophrenia. In line with clinical
      observations, our findings support the notion that smoking modulates medication
      associated side effects on reward processing in patients with schizophrenia.

PMID- 23010840
TI  - Cardiorenal [corrected] syndrome: an emerging problem in pediatric critical care.
AB  - The cardiorenal syndrome (CRS) refers to a complex pathophysiologic state in
      which heart and kidney dysfunction coexist. Although a robust amount of adult
      literature exists, limited reports have been made regarding CRS in pediatric
      patients. However, CRS is increasingly being recognized as an impactful clinical
      problem that can have important implications regarding the need for treatment and
      prognosis. Although wide acceptance of a unified definition of CRS is lacking, a
      general consensus exists that CRS can be either primarily caused by cardiac
      disease with secondary effects on the kidney, or vice versa, as well as systemic
      conditions in which cardiac and renal disease are both considered to be
      secondary. Convincing data in the pediatric perioperative population have been
      reported, but there is a paucity of information in acute and chronic heart
      failure (HF), as well as acute kidney injury (AKI) and chronic kidney disease
      (CKD). Herein, we briefly report on the adult literature and summarize the
      current pediatric experience.

PMID- 23010841
TI  - Improving species-specific IDMS: the advantages of triple IDMS.
AB  - Triple isotope dilution mass spectrometry (triple IDMS) has been applied for the
      first time on protein quantification, especially on transferrin. Transferrin as
      an acute phase protein is a marker for several inflammation processes in the
      human body. Therefore, in Germany, the accurate and precise measurement of this
      important analyte is required. In this work, a new approach to triple IDMS is
      described and compared to double IDMS. Also, complete uncertainty budgets for
      both methods were set up to demonstrate the ability of this method to be used as
      a reference procedure. The relative expanded uncertainty (k=2) for triple IDMS
      (3.6 %) is smaller than the one for double IDMS (4.0 %). The content of
      transferrin found in the human serum reference material ERM-DA470k/IFCC ((2.41+/
      0.08) g/kg) with both methods was in good agreement with each other and with the
      certificate. For triple IDMS ((2.426+/-0.086) g/kg) and for double IDMS ((2.317+/
      0.092) g/kg), transferrin was determined. Although triple IDMS is a little more
      time consuming compared to double IDMS, there is the advantage that the isotopic
      composition of the spike material does not have to be determined. This is very
      useful especially in case of a marginal isotopic enrichment in the spike or
      problems with the accurate measurement of the spike isotope ratio.

PMID- 23010842
TI  - A modified lead-matrix separation procedure shown for lead isotope analysis in
      Trojan silver artefacts as an example.
AB  - A modified Pb-matrix separation procedure using NH4HCO3 solution as eluent has
      been developed and validated for determination of Pb isotope amount ratios by
      thermal ionization mass spectrometry. The procedure is based on chromatographic
      separation using the Pb.Spec resin and an in-house-prepared NH4HCO3 solution
      serving as eluent. The advantages of this eluent are low Pb blanks (<40 pg mL(
      1)) and the property that NH4HCO3 can be easily removed by use of a heating step
      (>60  degrees C). Pb recovery is >95 % for water samples. For archaeological
      silver samples, however, the Pb recovery is reduced to approximately 50 %, but
      causes no bias in the determination of Pb isotope amount ratios. The validated
      procedure was used to determine lead isotope amount ratios in Trojan silver
      artefacts with expanded uncertainties (k = 2) <0.09 %.

PMID- 23010843
TI  - Isotopic labeling-assisted metabolomics using LC-MS.
AB  - Metabolomics has emerged as the latest of the so-called "omics" disciplines and
      has great potential to provide deeper understanding of fundamental biochemical
      processes at the biological system level. Among recent technological
      developments, LC-HRMS enables determination of hundreds to thousands of
      metabolites over a wide range of concentrations and has developed into one of the
      most powerful techniques in non-targeted metabolomics. The analysis of mixtures
      of in-vivo-stable isotopic-labeled samples or reference substances with un
      labeled samples leads to specific LC-MS data patterns which can be systematically
      exploited in practically all data-processing steps. This includes recognition of
      true metabolite-derived analytical features in highly complex LC-MS data and
      characterization of the global biochemical composition of biological samples. In
      addition, stable-isotopic labeling can be used for more accurate quantification
      (via internal standardization) and identification of compounds in different
      organisms.

PMID- 23010844
TI  - Simultaneous enantiomeric determination of MDMA and its phase I and phase II
      metabolites in urine by liquid chromatography-tandem mass spectrometry with
      chiral derivatization.
AB  - A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI
      MS/MS) procedure was developed for the simultaneous determination of enantiomers
      of the prevalent designer drug 3,4-methylenedioxymethamphetamine (MDMA) and its
      phase I and phase II metabolites in urine with chiral derivatization. The
      analytes in urine were directly derivatized with chiral Marfey's reagent,
      N(alpha)-(5-fluoro-2,4-dinitrophenyl)-D-leucinamide, without extraction. The
      diastereomers of the N(alpha)-(2,4-dinitrophenyl)-D-leucinamide derivatives
      generated were determined by LC-MS/MS. Satisfactory chromatographic separation
      was achieved for the enantiomers of MDMA and its metabolites 3,4
      methylenedioxyamphetamine, 4-hydroxy-3-methoxymethamphetamine (HMMA), HMMA
      glucuronide, and HMMA sulfate on a semimicro octadecylsilane column using linear
      gradient elution. With use of multiple reaction monitoring mode, the limits of
      detection of these analytes ranged from 0.01 to 0.03 MUg/mL. Linear calibration
      curves were obtained for all enantiomers from 0.1 to 20 MUg/mL in urine. The
      method showed sufficient reproducibility and quantitative ability. This is the
      first report of a simple LC-MS/MS-based analytical procedure with direct chiral
      derivatization in aqueous media that allows simultaneous enantiomeric
      determination of drugs and their metabolites, including glucuronide and sulfate
      derivatives.

PMID- 23010845
TI  - Biocatalytic reactors based on ribonuclease A immobilized on macroporous
      monolithic supports.
AB  - Immobilized enzyme reactors (IMERs) produced by the covalent attachment of
      ribonuclease A to macroporous methacrylate-based monolithic supports using
      different experimental approaches are discussed and compared. Enzyme
      immobilization was carried out by direct covalent binding, as well as through
      attachment via a polymer spacer. The kinetic properties of an IMER operating in
      either recirculation mode or zonal elution mode were studied. Additionally, the
      effect of flow rate on the bioconversion efficiency of each IMER sample was
      examined.

PMID- 23010846
TI  - Development of a novel method for quantification of sterols and oxysterols by
      UPLC-ESI-HRMS: application to a neuroinflammation rat model.
AB  - Cholesterol and oxysterols are involved as key compounds in the development of
      severe neurodegenerative diseases and in neuroinflammation processes. Monitoring
      their concentration changes under pathological conditions is of interest to get
      insights into the role of lipids in diseases. For numerous years, liquid
      chromatography coupled to mass spectrometry has been the method of choice for
      metabolites identification and quantification in biological samples. However,
      sterols and oxysterols are relatively apolar molecules poorly adapted to
      electrospray ionization (ESI). To circumvent this drawback, we developed a novel
      and robust analytical method involving derivatization of these analytes in
      cholesteryl N-4-(N,N-dimethylamino)phenyl carbamates under alkaline conditions
      followed by ultra-performance liquid chromatography-high resolution mass
      spectrometry analysis (UPLC-HRMS). Optimized UPLC conditions led to the
      separation of a mixture of 11 derivatized sterols and oxysterols especially side
      chain substituted derivatives after 6 min of chromatographic run. High
      sensitivity time-of-flight mass analysis allowed analytes to be detected in the
      nanomolar range. The method was validated for the analysis of oxysterols and
      sterols in mice brain in respect of linearity, limits of quantification,
      accuracy, precision, analyte stability, and recovery according to the Food and
      Drug Administration (FDA) guidelines. The developed method was successfully
      applied to investigate the impact of lipopolysaccharide (LPS) treatment on the
      rat cerebral steroidome.

PMID- 23010847
TI  - Dual-color bioluminescent bioreporter for forensic analysis: evidence of
      androgenic and anti-androgenic activity of illicit drugs.
AB  - Bioassays represent promising complementary techniques to conventional analytical
      approaches used in doping analysis to detect illicit drugs like anabolic
      androgenic steroids (AAS). The fact that all AAS share a common mechanism of
      action via the human androgen receptor (hAR) enables the use of bioassays,
      relying on the activation of hAR as antidoping screening tools. Previously, we
      developed a dual-color bioreporter based on yeast cells engineered to express hAR
      and androgen response elements driving the expression of the bioluminescent (BL)
      reporter protein Photinus pyralis luciferase. A second reporter protein, the red
      emitting luciferase PpyRE8, was introduced in the bioreporter as internal
      viability control. Here, we report the first forensic application of a
      straightforward, accurate, and cost-effective bioassay, relying on spectral
      resolution of the two BL signals, in 96-microwell format. The bioreporter
      responds to dihydrotestosterone as reference androgen in a concentration
      dependent manner from 0.08 to 1,000 nM with intra- and inter-assay variation
      coefficients of 11.4 % and 13.1 %, respectively. We also demonstrated the
      suitability of this dual-color bioreporter to assess (anti)-androgenic activity
      of pure AAS, mixtures of AAS, and other illicit drugs provided by the Scientific
      Police. Significant anti-androgenic activity was observed in samples labeled as
      marijuana and hashish, containing Delta(9)-tetrahydrocannabinol as major
      constituent.

PMID- 23010848
TI  - Intrinsic single-band upconversion emission in colloidal Yb/Er(Tm):Na3Zr(Hf)F7
      nanocrystals.
AB  - Novel Yb/Er(Tm):Na(3)MF(7) (M = Zr, Hf) nanocrystals with intrinsic single-band
      upconversion emission, in contrast to the routine lanthanide-doped fluoride
      nanocrystals which show typical multi-band upconversion emissions, are reported
      for the first time. Specifically, the red upconversion intensity of the
      Yb/Er:Na(3)ZrF(7) nanocrystals is about 5 times as high as that of the hexagonal
      Yb/Er:NaYF(4) ones with a similar crystal size.

PMID- 23010849
TI  - Plasma glutathione peroxidase (GSH-Px) concentration is elevated in rheumatoid
      arthritis: a case-control study.
AB  - Plasma glutathione peroxidase (GSH-Px) by enzyme-linked immunosorbent assay
      (ELISA) offers a complimentary measurement approach to traditional GSH-Px
      activity methods. The aim was to investigate whether GSH-Px measured by ELISA in
      rheumatoid arthritis patients was elevated compared to controls. This was a case
      control study with rheumatoid arthritis patients recruited from private practice
      and gender and age-matched controls randomly selected from the electoral role.
      GSH-Px concentration was measured by ELISA. Plasma malondialdehyde was used as a
      measure of oxidative stress, and antioxidant capacity was measured based on
      reduction of Cu(++) to Cu(+) by antioxidants in the sample. Disease severity was
      measured using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and
      C-reactive protein was measured using an immunoturbidometric method. A total of
      74 patients were recruited, consisting of 35 rheumatoid arthritis cases and 39
      healthy controls. There were no differences between rheumatoid arthritis cases
      and controls for oxidative stress and antioxidant capacity; however, GSH-Px
      concentration was markedly elevated in the rheumatoid arthritis sufferers (85.9
      +/- 147.7 versus 17.3 +/- 13.0 mg/L, respectively; mean +/- SD; p < 0.01). GSH-Px
      levels were not associated with severity measured by the HAQ-DI or C-reactive
      protein. Patients with rheumatoid arthritis demonstrated increased GSH-Px
      consistent with an adaptive upregulation of GSH-Px to protect against oxidative
      stress.

PMID- 23010850
TI  - Acute and long-term effect of infliximab on humoral and echocardiographic
      parameters in patients with chronic inflammatory diseases.
AB  - Tumor necrosis factor alpha (TNF-alpha) plays an important role in the
      pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA),
      ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC).
      Anti-TNF-alpha strategies are successfully used in their treatment. However,
      their effect on heart function is still uncertain. The objectives of the study
      were to examine the acute and long-term effect of infliximab on the heart
      morphology and function in patients with chronic inflammatory disorders. Thirty
      one patients (21 men and 10 women) were included. Ten percent of them were
      diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC,
      respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP)
      was measured before and immediately after infliximab administration at the
      beginning of the study and in the sixth and 12th months. Echocardiography was
      performed at baseline and in the sixth and 12th months. There was a significant
      increase in NT-proBNP after the first infliximab infusion (88.40 +/- 14.09 vs.
      95.24 +/- 14.28 pg/ml, p = 0.0046) and similar response was detected after each
      infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not
      significantly decreased (88.40 +/- 14.09 vs. 81.74 +/- 23.14 pg/ml, p = 0.583,
      and 88.40 +/- 14.09 vs. 56.83 +/- 17.77 pg/ml, p = 0.0576, in the sixth and 12th
      months, respectively). There were no significant changes in echocardiographic
      structural and functional parameters of the left ventricle during follow-up.
      Plasma NT-proBNP mildly but significantly increases immediately after infliximab
      infusion. However, long-term infliximab administration does not deteriorate both
      cardiac morphology and function.

PMID- 23010851
TI  - Disposition and metabolism of 14C-dovitinib (TKI258), an inhibitor of FGFR and
      VEGFR, after oral administration in patients with advanced solid tumors.
AB  - PURPOSE: This study investigated the metabolism and excretion of dovitinib
      (TKI258), a tyrosine kinase inhibitor that inhibits fibroblast, vascular
      endothelial, and platelet-derived growth factor receptors, in patients with
      advanced solid tumors. METHODS: Four patients (cohort 1) received a single 500 mg
      oral dose of (14)C-dovitinib, followed by the collection of blood, urine, and
      feces for <=10 days. Radioactivity concentrations were measured by liquid
      scintillation counting and plasma concentrations of dovitinib by liquid
      chromatography-tandem mass spectrometry. Both techniques were applied for
      metabolite profiling and identification. A continuous-dosing extension phase
      (nonlabeled dovitinib 400 mg daily) was conducted with the 3 patients from cohort
      1 and 9 additional patients from cohort 2. RESULTS: The majority of radioactivity
      was recovered in feces (mean 61 %; range 52-69 %), as compared with urine (mean
      16 %; range 13-21 %). Only 6-19 % of the radioactivity was recovered in feces as
      unchanged dovitinib, suggesting high oral absorption. (14)C-dovitinib was
      eliminated predominantly via oxidative metabolism, with prominent primary
      biotransformations including hydroxylation on the fluorobenzyl ring and N
      oxidation and carbon oxidation on the methylpiperazine moiety. Dovitinib was the
      most prominent radioactive component in plasma. The high apparent volume of
      distribution (2,160 L) may indicate that dovitinib distributes extensively to
      tissues. Adverse events were predominantly mild to moderate, and most common
      events included nausea, vomiting, constipation, diarrhea, and fatigue.
      CONCLUSIONS: Dovitinib was well absorbed, extensively distributed, and eliminated
      mainly by oxidative metabolism, followed by excretion, predominantly in feces.
      The adverse events were as expected for this class of drug.

PMID- 23010852
TI  - Phase II study of irinotecan and cisplatin with concurrent split-course
      radiotherapy in limited-disease small cell lung cancer.
AB  - BACKGROUND: Irinotecan and cisplatin are one of active regimens for patients with
      extensive-stage small cell lung cancer (SCLC). To determine the efficacy and
      toxicity of irinotecan and cisplatin with concurrent split-course thoracic
      radiotherapy in limited-disease (LD) SCLC, we conducted a phase II study.
      PATIENTS AND METHODS: Thirty-four patients fulfilling the following eligibility
      criteria were enrolled: chemotherapy-naive, good performance status (PS 0-1), age
      <=75, LD-SCLC, and adequate organ function. The patients received irinotecan 40
      mg/m(2) i.v. on days 1, 8, and 15, and cisplatin 60 mg/m(2) i.v. on day 1. Four
      cycles of chemotherapy were repeated every 4 weeks. Split-course thoracic
      radiotherapy of once-daily 2 Gy/day commenced on day 2 of each chemotherapy
      cycle, with 26 and 24 Gy administered in the first and second cycles,
      respectively. RESULTS: Thirty-four patients were eligible and assessable for
      response, toxicity, and survival. Patients' characteristics were as follows:
      male/female = 29/5; PS 0/1 = 18/16; median age (range) = 67 (50-73); and stage
      IB/IIA/IIB/IIIA/IIIB = 2/2/3/16/11. The overall response was 100 % (CR 8, PR 26).
      Grade 4 leukopenia, neutropenia, grade 3-5 pneumonitis, diarrhea, and esophagitis
      occurred in 24, 38, 6, 3, and 0 %, respectively. There were 2 treatment-related
      deaths from pneumonitis. The median time to tumor progression was 14.3 months.
      The median overall survival time and the 2- and 5-year survival rates were 44.5
      months, 66.7 and 46.1 %, respectively. No tumor progression was observed in
      patients with CR. CONCLUSION: Irinotecan plus cisplatin with concurrent split
      course thoracic radiotherapy was effective and tolerable in untreated LD-SCLC.

PMID- 23010853
TI  - Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic
      impairment.
AB  - PURPOSE: The aim of this study was to determine the plasma pharmacokinetics of
      eribulin mesylate in patients with solid tumors with mild and moderate hepatic
      impairment. PATIENTS AND METHODS: A phase I, pharmacokinetic study was performed
      in patients with advanced solid tumors and normal hepatic function or Child-Pugh
      A (mild) or Child-Pugh B (moderate) hepatic impairment. Treatments were given on
      day 1 and 8 of a 21-day cycle and consisted of 1.4, 1.1 and 0.7 mg/m(2) eribulin
      mesylate, for normal hepatic function, Child-Pugh A and B hepatic impairment,
      respectively. Also safety and anti-tumor activity were determined. RESULTS:
      Hepatic impairment increased exposure to eribulin. In patients with Child-Pugh A
      (N = 7) and Child-Pugh B (N = 5), mean dose-normalized AUC(0-infinity) was 1.75
      fold (90 % confidence intervals (CI): 1.16-2.65) and 2.48-fold (90 % CI: 1.57
      3.92) increased, respectively, compared with patients who have normal function (N
      = 6). The most frequently reported treatment-related events were alopecia (12/18)
      and fatigue (7/18) and these were observed across all groups. Nine patients (50
      %) had stable disease as best response. CONCLUSIONS: A reduced dose of 1.1 and
      0.7 mg/m(2) of eribulin mesylate is recommended for patients with Child-Pugh A or
      B hepatic impairment, respectively.

PMID- 23010854
TI  - [Stroke always with an emergency physician? - Pro].
AB  - Good management of acute stroke is dependent on time and expertise. In Germany
      emergency medical care by ambulance services sometimes occurs without an
      emergency physician being sent to the scene. By reviewing current literature the
      question of patient care in the ambulance with or without an emergency physician
      is discussed. Presence of an emergency physician at the scene results in high
      diagnostic accuracy, allows for invasive procedures to be carried out, and
      enables referral to a specialist centre with a stroke-unit. The "rendezvous"
      system of separate deployment of patient ambulance and emergency physician allow
      flexible assignment of the physician resulting in short response times. Current
      research does not support a turn away from the deployment of an emergency
      physician in cases of acute stroke.

PMID- 23010855
TI  - [Condition following tongue cancer, persistent pleural effusion and bilateral
      lung nodules].

PMID- 23010856
TI  - [Update on tracheotomy].
AB  - Tracheotomy in mechanically ventilated critically ill patients is a procedure
      commonly performed in the intensive care unit. The aim is to facilitate
      respiratory weaning and improve clinical outcome by reducing side effects of
      prolonged invasive mechanical ventilation and sedation. At the same time, the
      risk of tracheotomy associated complications must be minimized. Indications,
      method and timing must be individualized for each patient. Main determinants for
      decision-making, success and safety are the expected individual clinical
      benefits, the patient risk factors for complications and aspects of local
      experience and logistics. This review summarizes current concepts and evidence.

PMID- 23010857
TI  - Multi-GPU Jacobian accelerated computing for soft-field tomography.
AB  - Image reconstruction in soft-field tomography is based on an inverse problem
      formulation, where a forward model is fitted to the data. In medical
      applications, where the anatomy presents complex shapes, it is common to use
      finite element models (FEMs) to represent the volume of interest and solve a
      partial differential equation that models the physics of the system. Over the
      last decade, there has been a shifting interest from 2D modeling to 3D modeling,
      as the underlying physics of most problems are 3D. Although the increased
      computational power of modern computers allows working with much larger FEM
      models, the computational time required to reconstruct 3D images on a fine 3D FEM
      model can be significant, on the order of hours. For example, in electrical
      impedance tomography (EIT) applications using a dense 3D FEM mesh with half a
      million elements, a single reconstruction iteration takes approximately 15-20 min
      with optimized routines running on a modern multi-core PC. It is desirable to
      accelerate image reconstruction to enable researchers to more easily and rapidly
      explore data and reconstruction parameters. Furthermore, providing high-speed
      reconstructions is essential for some promising clinical application of EIT. For
      3D problems, 70% of the computing time is spent building the Jacobian matrix, and
      25% of the time in forward solving. In this work, we focus on accelerating the
      Jacobian computation by using single and multiple GPUs. First, we discuss an
      optimized implementation on a modern multi-core PC architecture and show how
      computing time is bounded by the CPU-to-memory bandwidth; this factor limits the
      rate at which data can be fetched by the CPU. Gains associated with the use of
      multiple CPU cores are minimal, since data operands cannot be fetched fast enough
      to saturate the processing power of even a single CPU core. GPUs have much faster
      memory bandwidths compared to CPUs and better parallelism. We are able to obtain
      acceleration factors of 20 times on a single NVIDIA S1070 GPU, and of 50 times on
      four GPUs, bringing the Jacobian computing time for a fine 3D mesh from 12 min to
      14 s. We regard this as an important step toward gaining interactive
      reconstruction times in 3D imaging, particularly when coupled in the future with
      acceleration of the forward problem. While we demonstrate results for EIT, these
      results apply to any soft-field imaging modality where the Jacobian matrix is
      computed with the adjoint method.

PMID- 23010859
TI  - Cell membrane conformation at vertical nanowire array interface revealed by
      fluorescence imaging.
AB  - The perspectives offered by vertical arrays of nanowires for biosensing
      applications in living cells depend on the access of individual nanowires to the
      cell interior. Recent results on electrical access and molecular delivery suggest
      that direct access is not always obtained. Here, we present a generic approach to
      directly visualize the membrane conformation of living cells interfaced with
      nanowire arrays, with single nanowire resolution. The method combines confocal z
      stack imaging with an optimized cell membrane labelling strategy which was
      applied to HEK293 cells interfaced with 2-11 MUm long and 3-7 MUm spaced
      nanowires with various surface coatings (bare, aminosilane-coated or
      polyethyleneimine-coated indium arsenide). We demonstrate that, for all commonly
      used nanowire lengths, spacings and surface coatings, nanowires generally remain
      enclosed in a membrane compartment, and are thereby not in direct contact with
      the cell interior.

PMID- 23010860
TI  - Pregnancy and birth outcome improvements for American Indians in the Healthy
      Start project of the Inter-Tribal Council of Michigan, 1998-2008.
AB  - American Indians living in Michigan experience disproportionately high rates of
      infant mortality. This 11-year (1998-2008) cohort study evaluated impacts of a
      Healthy Start (HS) program administered by the Inter-Tribal Council of Michigan
      (ITCM) on perinatal outcomes. Women who enrolled in ITCM's HS program ("exposed")
      were compared with non-enrolled ("unexposed") for four outcomes: low birth weight
      (LBW), small for gestational age, preterm birth, and inadequate prenatal care. To
      classify exposed and unexposed women and their children, Michigan vital records
      data were linked with HS enrollment records to identify participants and non
      participants among all American Indian births. Logistic regression was used to
      calculate odds ratios for the four outcomes of interest. Analyses were stratified
      for high and low access to care based on Medically Underserved Area (MUA)
      designation for a woman's county of residence. Of 4,149 American Indian births
      during the period, 872 were to women who enrolled prenatally in HS. Although
      unstratified analysis showed no differences between HS participants and non
      participants, stratified analyses demonstrated that participants from MUA
      counties had decreased odds of LBW and inadequate prenatal care. Results suggest
      that in MUA counties where participants and non-participants are at similar risk
      for poor outcomes, HS may be reducing barriers and improving outcomes. In non-MUA
      counties participants had similar outcomes as non-participants. These results may
      reflect a wider disparity in risk factors between the two groups in non-MUA
      counties. The complex interplay among need, access, and benefit complicates
      analyses and suggests the importance of more in-depth and focused studies. 

PMID- 23010861
TI  - Correlates of high perceived stress among pregnant Hispanic women in Western
      Massachusetts.
AB  - Prenatal psychosocial stress has been associated with adverse pregnancy outcomes,
      even after controlling for known risk factors. This paper aims to evaluate
      correlates of high perceived stress among Hispanic women, a group with elevated
      rates of stress during pregnancy. We conducted this analysis among 1,426 pregnant
      Hispanic women using data from Proyecto Buena Salud, a prospective cohort study
      conducted in Western Massachusetts. Cohen's Perceived Stress Scale (PSS-14)
      validated in English and Spanish was administered in early (mean = 12.4 weeks
      gestation), mid (mean = 21.3 weeks gestation) and late (mean = 30.8 weeks
      gestation) pregnancy at which time bilingual interviewers collected data on socio
      demographic, acculturation, behavioral, and psychosocial factors. High perceived
      stress was defined as a PSS score >30. Young maternal age (odds ratio (OR) = 0.6;
      95 % confidence interval (CI) 0.4-0.9 for <19 vs. 19-23 years), pre-pregnancy
      consumption of alcohol (OR = 2.2; 95 % CI 1.4-3.5 for >12 drinks/month vs. none)
      and smoking (OR = 2.2; 95 % CI 1.3-3.7 for >10 cigarettes/day vs. none) were
      associated with high perceived stress during early pregnancy. Furthermore, higher
      annual household income (OR = 0.4; 95 % CI 0.1-0.9 for >$30,000 vs. <$15,000),
      greater number of adults in the household (OR = 1.8; 95 % CI 1.1-3.0 for >=3 vs.
      1) and language preference (OR = 0.6; 95 % CI 0.4-0.9 for Spanish vs. English)
      were associated with high stress during mid-pregnancy. Likewise, annual household
      income was inversely associated with high stress during late pregnancy. Our
      results have important implications for incorporation of routine screening for
      psychosocial stress during prenatal visits and implementation of psychosocial
      counseling services for women at high risk.

PMID- 23010862
TI  - Association between smoking cessation interventions during prenatal care and
      postpartum relapse: results from 2004 to 2008 multi-state PRAMS data.
AB  - Cigarette smoking is a serious global public health issue, and is particularly
      harmful to the maternal and child population. The study aimed to determine if
      there was an association between smoking cessation intervention during pregnancy
      and postpartum smoking relapse, and to define a time trend of postpartum smoking
      relapse after delivery. Data from the 2004-2008 pregnancy risk assessment
      monitoring systems of Colorado, Maine, Ohio, and Washington were analyzed.
      Logistic regression was used to define the association between smoking cessation
      intervention and postpartum smoking relapse, and to identify trend of postpartum
      smoking relapse. Analyses were done using SAS-Callable SUDAAN v.10.0 and Mplus
      v.6.0. Among the 2,938 women in the study the relapse rate was 48 %. It was 45 %
      among those without intervention, 58 % among those who received only counseling,
      and 57 % among those who received both counseling with treatment and/or referral.
      The rate was 42, 61, and 67 % among women whose infants were at 2-3, 4-5, and 6
      months or more, respectively. Adjusted logistic regression models showed a trend
      of increased smoking relapse, but did not indicate an association between smoking
      cessation intervention and smoking relapse. Rates of smoking relapse were high
      and increased by time after delivery. Smoking cessation intervention during
      pregnancy may not be successful at preventing postpartum smoking relapse. 

PMID- 23010863
TI  - Subcutaneous body fat in pregnant New Zealand women: association with wheeze in
      their infants at 18 months.
AB  - To investigate the association of subcutaneous body fat levels in pregnant women
      with wheezing in their 18 month old infants. A prospective study of European and
      Polynesian volunteers (n = 369) recruited from northern New Zealand were visited
      in months 4 and 7 of pregnancy when height, weight, and triceps, biceps and
      costal skinfolds were measured, and questionnaires determining personal details
      administered; and again visited 18 months after birth when infants were measured
      and questions on infant feeding and wheeze administered. At 18 months 32 % of
      infants had wheezed in the past 12 months. Increased wheeze was associated with
      maternal asthma, eczema or allergy (p = 0.001); receiving family welfare payments
      (p = 0.010); and being Polynesian (p = 0.021); while exclusive breastfeeding to 2
      months (p = 0.045) was associated with decreased wheeze. Individual month 4 and
      month 7 mean triceps, biceps and costal skinfolds were all greater in mothers of
      wheezers compared to nonwheezers, biceps and costal skinfolds significantly so (p
      = 0.002, p = 0.005 at month 7). The sum of these skinfolds at month 4, at month
      7, and the difference between these sums, were all significantly associated with
      increased risk of infant wheeze at 18 months when considered alone (p = 0.037, p
      = 0.001 and p = 0.015) or in combination. Prevalence of infant wheeze was 22.7 %
      for mothers with lower quartile month 7 skinfolds, compared to 45.0 % for mothers
      with upper quartile. After adjusting for significant covariates the difference in
      skinfolds had the strongest association (p = 0.003) followed by sum at month 4 (p
      = 0.074 or 0.003 depending on whether Polynesian ethnicity was included in the
      model). The sum of skinfolds declined between month 4 and month 7 in 34 % of
      women. Prevalence of wheeze was 19.2 % where the difference in mothers' skinfolds
      between month 4 and month 7 decreased by 10 mm or more and 41.7 % where the
      difference increased by 10 mm or more. Mean month 4 weights, BMI and sum of
      skinfolds were below average in the latter group. As the sum of month 4 or month
      7 maternal skinfolds increased the prevalence of infant wheeze increased. In
      addition as the change in skinfolds between month 4 and month 7 became more
      positive the prevalence of infant wheeze increased. This study suggests for the
      first time that changes in subcutaneous fat during pregnancy are associated with
      prevalence of infant wheeze.

PMID- 23010864
TI  - Measuring dosage: a key factor when assessing the relationship between prenatal
      case management and birth outcomes.
AB  - To assess whether a measure of prenatal case management (PCM) dosage is more
      sensitive than a dichotomous PCM exposure measure when evaluating the effect of
      PCM on low birthweight (LBW) and preterm birth (PTB). We constructed a
      retrospective cohort study (N = 16,657) of Iowa Medicaid-insured women who had a
      singleton live birth from October 2005 to December 2006; 28 % of women received
      PCM. A PCM dosage measure was created to capture duration of enrollment, total
      time with a case manager, and intervention breadth. Propensity score (PS)
      adjusted odds ratios (ORs), and 95 % confidence intervals (95 % CIs) were
      calculated to assess the risk of each outcome by PCM dosage and the dichotomous
      PCM exposure measure. PS-adjusted ORs of PTB were 0.88 (95 % CI 0.70-1.11), 0.58
      (95 % CI 0.47-0.72), and 1.43 (95 % CI 1.23-1.67) for high, medium, and low PCM
      dosage, respectively. For LBW, the PS-adjusted ORs were 0.76 (95 % CI 0.57-1.00),
      0.64 (95 % CI 0.50-0.82), and 1.36 (95 % CI 1.14-1.63), for high, medium, and low
      PCM dosage, respectively. The PCM dichotomous participation measure was not
      significantly associated with LBW (OR = 0.95, 95 % CI 0.82-1.09) or PTB (0.97, 95
      % CI 0.87-1.10). The reference group in each analysis is No PCM. PCM was
      associated with a reduced risk of adverse pregnancy outcomes for Medicaid-insured
      women in Iowa. PCM dosage appeared to be a more sensitive measure than the
      dichotomous measure of PCM participation. 

PMID- 23010865
TI  - Chronic l-arginine treatment improves metabolic, cardiovascular and liver
      complications in diet-induced obesity in rats.
AB  - l-Arginine is an important dietary amino acid in both health and disease,
      especially of the cardiovascular system. This study has determined whether
      dietary supplementation with l-arginine attenuates cardiovascular, metabolic,
      pancreatic and liver changes in a rat model of the human metabolic syndrome. Male
      Wistar rats (8-9 weeks old) were divided into four groups. Two groups of rats
      were fed a corn starch-rich diet (C) whereas the other two groups were given a
      high carbohydrate, high fat diet (H) with 25% fructose in the drinking water, for
      16 weeks. One group fed each diet was supplemented with 5% l-arginine in the food
      for the final 8 weeks of this protocol. The corn starch diet (C) contained ~68%
      carbohydrates mainly as polysaccharides, while the high-carbohydrate, high-fat
      diet contained ~68% carbohydrates mainly as fructose and sucrose together with
      24% fat mainly as saturated and monounsaturated fats from beef tallow. The high
      carbohydrate, high-fat diet-fed rats showed the symptoms of metabolic syndrome
      including obesity and hypertension with heart and liver damage. Supplementation
      with l-arginine attenuated impairment in left ventricular and liver structure and
      function, glucose tolerance, and decreased blood pressure, abdominal fat pads,
      inflammatory cell infiltration, pancreatic cell hypertrophy and oxidative stress.
      This study indicates that oral supplementation with l-arginine attenuated or
      normalised obesity-related changes in the heart, liver and pancreas by reducing
      inflammation and oxidative stress associated with high carbohydrate, high fat
      feeding in rats.

PMID- 23010866
TI  - SWI/SNF complex in disorder: SWItching from malignancies to intellectual
      disability.
AB  - Heterozygous germline mutations in components of switch/sucrose nonfermenting
      (SWI/SNF) chromatin remodeling complexes were recently identified in patients
      with non-syndromic intellectual disability, Coffin-Siris syndrome and Nicolaides
      Baraitser syndrome. The common denominator of the phenotype of these patients is
      severe intellectual disability and speech delay. Somatic and germline mutations
      in SWI/SNF components were previously implicated in tumor development. This
      raises the question whether patients with intellectual disability caused by
      SWI/SNF mutations in the germline are exposed to an increased risk of developing
      cancer. Here we compare the mutational spectrum of SWI/SNF components in
      intellectual disability syndromes and cancer, and discuss the implications of the
      results of this comparison for the patients.

PMID- 23010867
TI  - Influence of pH, light cycle, and temperature on ecotoxicity of four sulfonylurea
      herbicides towards Lemna gibba.
AB  - In chemical regulation, e.g. the EU Water Framework Directive, REACH, or the
      Pesticide Directive, standardized ecotoxicological tests are applied to evaluate
      and rank the hazard of compounds and for deriving environmental quality standards
      (EQS). Standardized test methods prescribe fixed testing conditions e.g. specific
      temperature, pH, light intensity etc. However, environmental conditions under
      which the organisms live are rarely identical to the standard conditions. Thus,
      the ecotoxicity of compounds found in standard test is not only a function of the
      compounds inherent physico-chemical properties but is also affected by test
      conditions. It is therefore important to study the effect of changes in test
      conditions in order to get reliable input ecotoxicity data for assessing the
      potential risk posed by a compound. The objective of this study was to
      investigate the implications of changing test conditions on the toxicity of four
      sulfonylurea herbicides (SUs). The toxicity of the four SUs towards Lemna gibba
      was investigated at three pH levels (6, 7.5 and 9), at two temperatures (15 and
      24  degrees C) and two light regimes (continuous and 12:12 h light:dark cycle)
      The EC50 increased twofold to tenfold for the four SUs when pH was increased from
      6 to 9. Decreasing the temperature from 24 to 15  degrees C or introducing a
      dark:light cycle did not cause any trends in changes in toxicity. The results
      show that test conditions can have an effect on the toxicity and this should be
      considered when the standard test results are used for derivation of EQS.

PMID- 23010868
TI  - Side effects of two reduced-risk insecticides, indoxacarb and spinosad, on two
      species of Trichogramma (Hymenoptera: Trichogrammatidae) on cabbage.
AB  - Trichogramma pretiosum Riley and T. brassicae Bezdenko are common egg parasitoids
      of many lepidopteran pest species damaging vegetable, but their effectiveness can
      be severely curtailed by insecticide applications. To identify insecticides that
      are potentially compatible with these parasitoid species, the effects of
      indoxacarb and spinosad were bioassayed in the laboratory. The bioassays included
      exposure of adults to various aged residues on glass and cabbage leaf surfaces at
      different intervals after application, and direct spray on host eggs for effects
      on parasitism and development and mortality of parasitoid eggs, young and old
      larvae and pupae. The results showed that the glass- and leaf-surface residues of
      indoxacarb were harmless to both parasitoid species, whereas those of spinosad
      were moderately harmful to harmful to both parasitoid species depending on the
      rates used. The use of indoxacarb on host eggs did not affect significantly
      parasitism by both parasitoid species, whereas the higher rates of spinosad
      reduced parasitism. However, both insecticides did not affect immature
      development and adult emergence. Results from direct spray of host eggs with
      various immature stages inside showed that indoxacarb did not have significant
      effects on the egg, young and old larval stages and the pupal stage; whereas the
      high rates of spinosad when applied at the older larval and pupal stages
      significantly reduced adult emergence for both parasitoid species. Therefore,
      application of spinosad in an agro-ecosystem where Trichogramma are dominant
      should be carefully evaluated or avoided.

PMID- 23010869
TI  - Designing ionic liquids: the chemical structure role in the toxicity.
AB  - Ionic liquids (ILs) are a novel class of solvents with interesting
      physicochemical properties. Many different applications have been reported for
      ILs as alternatives to organic solvents in chemical and bioprocesses. Despite the
      argued advantage of having low vapor pressure, even the most hydrophobic ILs show
      some degree of solubility in water, allowing their dispersion into aquatic
      systems and raising concerns on its pollutant potential. Moreover, nowadays most
      widespread notion concerning the ILs toxicity is that there is a direct
      relationship with their hydrophobicity/lipophilicity. This work aims at enlarging
      the currently limited knowledge on ILs toxicity by addressing negative impacts in
      aquatic ecosystems and investigating the possibility of designing hydrophobic ILs
      of low ecotoxicity, by the manipulation of their chemical structures. The impact
      of aromaticity on the toxicity of different cations (pyridinium, piperidinium,
      pyrrolidinium and imidazolium) and hydrophobic anions
      (bis(trifluoromethylsulfonyl)imide [NTf(2)] and hexafluorophosphate [PF(6)]) was
      analysed. Concomitantly, several imidazolium-based ILs of the type [C( n )C( m
      )C( j )im][NTf(2)] were also studied to evaluate the effects of the position of
      the alkyl chain on the ILs' toxicity. For that purpose, standard assays were
      performed using organisms of different trophic levels, Vibrio fischeri,
      Pseudokirchneriella subcapitata and Daphnia magna, allowing to evaluate the
      consistency of the structure-activity relationships across different biological
      targets. The results here reported suggest the possibility of designing ILs with
      an enhanced hydrophobic character and lower toxicity, by elimination of their
      aromatic nature.

PMID- 23010870
TI  - Nondestructive indices of mercury exposure in three species of turtles occupying
      different trophic niches downstream from a former chloralkali facility.
AB  - Turtles are useful for studying bioaccumulative pollutants such as mercury (Hg)
      because they have long life spans and feed at trophic levels that result in high
      exposure to anthropogenic chemicals. We compared total Hg concentrations in blood
      and toenails of three species of turtles (Chelydra serpentina, Sternotherus
      odoratus, and Graptemys geographica) with different feeding ecologies from
      locations up- and downstream of a superfund site in Virginia, USA. Mercury
      concentrations in turtle tissues were low at the reference site (average +/- 1SE:
      blood = 48 +/- 6 ng g(-1); nail = 2,464 +/- 339 ng g(-1) FW) but rose near the
      contamination source to concentrations among the highest ever reported in turtles
      [up to 1,800 ng g(-1) (blood) and 42,250 ng g(-1) (nail) FW]. Tissue
      concentrations remained elevated ~130 km downstream from the source compared to
      reference concentrations. Tissue Hg concentrations were higher for C. serpentina
      and S. odoratus than G. geographica, consistent with the feeding ecology and our
      stable isotope (delta(13)C and delta(15)N) analyses of these species. In
      addition, we suggest that toenails were a better indication of Hg exposure than
      blood, probably because this keratinized tissue represents integrated exposure
      over time. Our results demonstrate that downstream transport of Hg from point
      sources can persist over vast expanses of river thereby posing potential exposure
      risks to turtles, but relative exposure varies with trophic level. In addition,
      our study identifies turtle toenails as a simple, cost-efficient, and minimally
      invasive tissue for conservation-minded sampling of these long-lived vertebrates.

PMID- 23010871
TI  - Association of global weather changes with acute coronary syndromes: gaining
      insights from clinical trials data.
AB  - The aim of this study was to develop a method for the identification of global
      weather parameters and patient characteristics associated with a type of heart
      attack in which there is a sudden partial blockage of a coronary artery. This
      type of heart attack does not demonstrate an elevation of the ST segment on an
      electrocardiogram and is defined as a non-ST elevation acute coronary syndrome
      (NSTE-ACS). Data from the Global Summary of the Day database was linked with the
      enrollment and baseline data for a phase III international clinical trial in NSTE
      ACS in four 48-h time periods covering the week prior to the clinical event that
      prompted enrollment in the study. Meteorological events were determined by
      standardizing the weather data from enrollment dates against an empirical
      distribution from the month prior. These meteorological events were then linked
      to the patients' geographic region, demographics and comorbidities to identify
      potential susceptible populations. After standardization, changes in temperature
      and humidity demonstrated an association with the enrollment event. Additionally
      there appeared to be an association with gender, region and a history of stroke.
      This methodology may provide a useful global insight into assessing the
      biometeorologic component of diseases from international data.

PMID- 23010872
TI  - Endothelialization approaches for viable engineered tissues.
AB  - One of the main limitation in obtaining thick, 3-dimensional viable engineered
      constructs is the inability to provide a sufficient and functional blood vessel
      system essential for the in vitro survival and the in vivo integration of the
      construct. Different strategies have been proposed to simulate the ingrowth of
      new blood vessels into engineered tissue, such as the use of growth factors,
      fabrication scaffold technologies, in vivo prevascularization and cell-based
      strategies, and it has been demonstrated that endothelial cells play a central
      role in the neovascularization process and in the control of blood vessel
      function. In particular, different "environmental" settings (origin, presence of
      supporting cells, biomaterial surface, presence of hemodynamic forces) strongly
      influence endothelial cell function, angiogenic potential and the in vivo
      formation of durable vessels. This review provides an overview of the different
      techniques developed so far for the vascularization of tissue-engineered
      constructs (with their advantages and pitfalls), focusing the attention on the
      recent development in the cell-based vascularization strategy and the in vivo
      applications.

PMID- 23010873
TI  - NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos
      induced mesothelioma.
AB  - Asbestos exposure can result in serious and frequently lethal diseases, including
      malignant mesothelioma. The host sensor for asbestos-induced inflammation is the
      NLRP3 inflammasome and it is widely assumed that this complex is essential for
      asbestos-induced cancers. Here, we report that acute interleukin-1beta production
      and recruitment of immune cells into peritoneal cavity were significantly
      decreased in the NLRP3-deficient mice after the administration of asbestos.
      However, NLRP3-deficient mice displayed a similar incidence of malignant
      mesothelioma and survival times as wild-type mice. Thus, early inflammatory
      reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in
      the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage
      carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance
      phenotype in two different strain backgrounds, suggesting a tumour-promoting role
      of NLRP3 in certain chemically-induced cancer types.

PMID- 23010874
TI  - How epigenetic imprinting contributes to stabilizing the Th2 phenotype.

PMID- 23010875
TI  - ADAM28 is elevated in humans with the metabolic syndrome and is a novel sheddase
      of human tumour necrosis factor-alpha.
AB  - Metalloproteinases are implicated in cleaving numerous proinflammatory mediators
      from the cell surface. Interestingly, the elevated levels of tumour necrosis
      factor-alpha (TNF-alpha) have been associated with the metabolic syndrome. We
      aimed to ascertain whether the human metalloproteinase ADAM28 correlates with
      parameters of the metabolic syndrome and whether ADAM28 is a novel sheddase of
      human TNF-alpha. To identify novel metalloproteinases associated with the
      metabolic syndrome, we conducted microarray studies on peripheral blood
      mononuclear cells from a well characterised human cohort. Human ADAM28 and TNF
      alpha were overexpressed and ADAM28 expression or activity was reduced with small
      interfering RNA (siRNA) or pharmacological inhibition. TNF-alpha levels were
      measured in cell supernatant by enzyme-linked immunosorbent assay. We also
      conducted ADAM28 inhibition studies in human THP-1 macrophages. Human ADAM28
      expression levels were positively correlated with parameters of the metabolic
      syndrome. When human ADAM28 and TNF-alpha were overexpressed in HEK293 cells,
      both proteins co-localised, co-immunoprecipitated and promoted TNF-alpha
      shedding. The shedding was significantly reduced when ADAM28 activity was
      inhibited or ADAM28 expression was downregulated. In human THP-1 macrophages,
      endogenous ADAM28 and TNF-alpha were co-expressed and TNF-alpha shedding was
      significantly reduced when ADAM28 was inhibited by pharmacological inhibition or
      siRNA knockdown. Our data suggest a novel mechanistic role for the
      metalloproteinase ADAM28 in inflammation, obesity and type 2 diabetes.

PMID- 23010876
TI  - Toxoplasmosis and neuropsychiatric diseases: can serological studies establish a
      clear relationship?
AB  - Toxoplasmosis is a widespread infection, with clinical spectrum ranging from a
      completely asymptomatic infection to multi-organ involvement. After entering the
      body, the parasite forms tissue cysts and establishes a chronic infection,
      involving also the central nervous system (CNS). During the last years, a lot of
      research has focused on the possible link between exposure to T. gondii and
      development of neuropsychiatric disorders such as schizophrenia and Parkinson's
      disease (PD). If a firm association between Toxoplasma infection and
      neuropsychiatric disorders will be established, this would lead to novel
      strategies for their prevention and treatment. We will review data from
      serological and neurodevelopment studies relating infection with T. gondii to
      such neuropsychiatric diseases.

PMID- 23010877
TI  - Epidemiology of headaches in Tehran urban area: a population-based cross
      sectional study in district 8, year 2010.
AB  - Many population-based studies have been performed to determine the prevalence of
      different types of headaches; however, none of them was performed in Tehran urban
      area as a huge and crowded metropolitan with multiple serious problematic crises.
      This study was performed to evaluate the prevalence rates of different types of
      headache among adult population of Tehran urban area in the year 2010. In this
      cross-sectional survey, a "face-to-face, in-door" structured interview was
      developed and used in district 8 of Tehran urban area as one representative
      region in the year 2010. A form concerning the prevalence of different types of
      headaches which also comprised the characteristics of the headaches and
      sociodemographic data was designed. After enrollment, participation rate of 91%
      (3,655 out of 4,000) was achieved. Of 3,655 recruited individuals, 2,778 (76%)
      people have experienced headache within last year. Tension-type headache and
      migraine were the most common types with the prevalence of 48.6% (n = 1,777) and
      18.2% (n = 665), while, chronic daily, medication overuse headache and cluster
      headaches were presented in 7.0% (n = 255), 4.9% (n = 180) and 0.1% (n = 3),
      respectively. The prevalence of primary headaches in a sample of Tehran adult
      population is considerable. This high prevalence of headaches necessitates
      further evaluation of possible risk factors derived from leaving in such a
      crowded metropolitan area.

PMID- 23010878
TI  - Myasthenia gravis developing in an HIV-negative patient with Kaposi's sarcoma.
AB  - Myasthenia gravis is a disorder of neuromuscular transmission caused by
      autoimmune mechanisms. We reported a possible association between seropositive
      myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed
      interactions between the treatment regimen for these two conditions. A 62-year
      old man came to our attention for ocular myasthenia gravis. He suffered from a
      classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms
      worsened, the patient was started on prednisone and azathioprine. The patient had
      a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were
      reduced and he was treated with vinblastine, with improvement both in
      dermatologic than in neurological symptomatology. We propose some considerations:
      the potential correlation between Kaposi's sarcoma and myasthenia gravis through
      immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of
      Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both
      the conditions.

PMID- 23010879
TI  - A selective fluorescent probe for thiols based on alpha,beta-unsaturated acyl
      sulfonamide.
AB  - We report herein a novel fluorescent probe based on alpha,beta-unsaturated acyl
      sulfonamide to detect thiols. The probe has good water solubility and reacts with
      thiols under aqueous conditions. It reacts selectively with cysteine but not with
      the other natural amino acids. The probe was subsequently applied to detect
      intracellular thiols.

PMID- 23010880
TI  - Characteristics of metabolically obese, normal-weight women differ by menopause
      status:  the Fourth Korea National Health and Nutrition Examination Survey.
AB  - OBJECTIVE: People with metabolically obese, normal-weight (MONW) phenotype,
      characterized by insulin resistance, are vulnerable to cardiovascular disease
      even though they are not physically obese. We assessed whether the
      characteristics of the MONW phenotype differed by menopause status in Korean
      women. METHODS: A nationally representative sample of 1,736 Korean women aged 19
      years or older (1,197 premenopausal women and 539 postmenopausal women), without
      diabetes, and with a body mass index of 18.5 to less than 25 kg/m were randomly
      selected from the Fourth Korean National Health and Nutrition Examination Survey
      in 2008. MONW individuals were defined as those included in the highest quartile
      of a homeostatic model assessment of insulin resistance. RESULTS: The prevalence
      of the MONW phenotype was highest (23.8%) in young women (<30 y) and decreased
      with age in premenopausal women. In postmenopausal women, there was a sharp
      increase in the prevalence of the MONW phenotype after the age of 60 years. After
      adjustment for covariates, including age, we found that young age, rural
      residence, high body mass index, high systolic blood pressure, low high-density
      lipoprotein cholesterol, high white blood cell count, and lack of regular
      exercise were significantly associated with the MONW phenotype in premenopausal
      women. However, for postmenopausal women, alanine aminotransferase was the only
      predictor that was independently associated with the MONW phenotype. CONCLUSIONS:
      The characteristics of the MONW phenotype seem to vary between premenopausal and
      postmenopausal women. This suggests that optimal clinical approaches to
      preventing cardiovascular disease in women with the MONW phenotype may differ
      according to menopause status.

PMID- 23010881
TI  - Protective effects of estrogen on ischemia/reperfusion-induced bladder
      dysfunction in female rabbits.
AB  - OBJECTIVE: The present study investigated the effects of ovarian hormone
      depletion and estrogen administration on ischemia/reperfusion (I/R)-induced
      bladder damage in female rabbits. METHODS: Female New Zealand white rabbits were
      divided into five groups. A sham surgical procedure was performed on rabbits in
      group 1. In group 2, both vesical arteries were clamped for 2 hours and then
      released (I/R surgical procedure). In group 3, 17beta-estradiol (100 MUg/kg/d)
      was injected intramuscularly before I/R surgical procedure. In group 4,
      ovariectomies were performed before I/R surgical procedure. Group 5 had
      ovariectomy, recovered for 2 weeks, and then received 17beta-estradiol for 2
      weeks. I/R surgical procedure was performed thereafter. Rabbits were killed 7
      days after I/R surgical procedure. Masson's trichrome stain was used, and
      immunohistochemical experiments were performed to evaluate interstitial fibrosis
      and intramural nerve changes. Western immunoblots were examined to determine the
      expressions of markers for inflammation, fibrosis, and oxidative stress. RESULTS:
      I/R surgical procedure decreased bladder contractile responses by 30% to 50%.
      Ovarian hormone depletion further reduced bladder contractile function by 45% to
      55% compared with the I/R group members that retained their ovaries. Moreover,
      I/R surgical procedure significantly decreased intramural neurofilament staining
      by two thirds compared with the control group. Estrogen replacement after
      ovariectomy significantly increased the density of nerve terminals. In addition,
      the expression of transforming growth factor-beta and fibronectin increased
      twofold and fivefold after I/R, respectively. Ovarian hormone depletion further
      increased the expression of these inflammatory and fibrosis markers. Ovariectomy
      significantly exacerbated oxidative damage, whereas estrogen replacement
      diminished oxidative stress to a level approaching that of the control group.
      CONCLUSIONS: I/R surgical procedure increases oxidative damage, enhances
      interstitial fibrosis, and results in bladder denervation. Ovarian hormone
      deficiency exacerbates this I/R-induced bladder damage, whereas estrogen therapy
      after ovariectomy attenuates this injury. These results reveal estrogen's
      protective effects on bladders subjected to I/R injury and the potential benefits
      of estrogen therapy on I/R-induced bladder damage.

PMID- 23010883
TI  - Impact of denosumab on the peripheral skeleton of postmenopausal women with
      osteoporosis:  bone density, mass, and strength of the radius, and wrist
      fracture.
AB  - OBJECTIVE: The aim of this study was to report the effects of denosumab on radius
      cortical and trabecular bone density, mass, and strength, and wrist fracture
      incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in
      Osteoporosis every 6 Months) study. METHODS: In the FREEDOM study, postmenopausal
      women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every
      6 months for 36 months. Radius bone mineral density (BMD), bone mineral content,
      and strength (polar moment of inertia) were evaluated in two prespecified
      substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n
      = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified
      analysis assessed wrist fracture incidence in all FREEDOM participants (placebo,
      N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those
      with higher fracture risk (baseline femoral neck T-score <=-2.5; placebo, N =
      1,406; denosumab, N = 1,384). RESULTS: Denosumab significantly increased areal
      BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone
      mineral content, and polar moment of inertia (assessed by quantitative CT),
      compared with placebo, in radius cortical and trabecular bone at all time points
      evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5%
      for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants
      with a femoral neck T-score of -2.5 or lower were at increased risk for wrist
      fracture, and denosumab significantly reduced wrist fracture incidence compared
      with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%;
      absolute risk reduction, 1.6%; P = 0.03). CONCLUSIONS: Denosumab significantly
      improves radius bone density, mass, and strength compared with placebo. In higher
      risk women, denosumab significantly reduces wrist fracture risk.

PMID- 23010885
TI  - [Treatment of bony avulsions of the posterior cruciate ligament (PCL) by a
      minimally invasive dorsal approach].
AB  - OBJECTIVE: Reduction and fixation of bony avulsions of the posterior cruciate
      ligament (PCL) through a minimally invasive dorsal approach to restore stability
      of the knee joint. Prevention of soft tissue damage through a minimally invasive
      procedure and achieving early functional rehabilitation by stable osteosynthesis.
      INDICATIONS: Bony tibial avulsions of the PCL and simple posteromedial tibial
      fractures. CONTRAINDICATIONS: Infections in or around the knee, critical soft
      tissue conditions and lack of patient compliance. OPERATION TECHNIQUE: Supine
      position, skin incision mediodorsal over the head of the medial gastrocnemius
      muscle. After dissection of soft tissue and superficial fascia the medial
      gasteocnemius muscle is retracted to the lateral side, nerves and vessels of the
      popliteal fossa are thereby protected. Incision of the posterior capsule from the
      tibial attachment, exposure of the fracture and the PCL, reduction of the
      fracture, fixation with two drill wires and definitive fixation with two
      cannulated screws. In case of multifragment fracture a suture anchor is used for
      fixation. POSTOPERATIVE MANAGEMENT: Partial weight bearing of 10-20 kg for 4-6
      weeks and limitation of knee flexion up to 90 degrees  for 4 weeks. RESULTS:
      Between November 2010 and November 2011 three patients were treated with the new
      minimally invasive posteromedial approach to fix bony avulsions of the PCL. In
      two cases an osteosynthesis with two screws was performed and in the other
      patient a comminuted avulsion fracture was fixed with a suture anchor. In the
      latter patient the posterolateral corner was additionally augmented according to
      Larson with an autologous semitendinosus tendon. No intraoperative or
      postoperative complications could be observed. In all three patients an excellent
      fracture reduction without steps or gaps could be achieved. In two cases an early
      functional treatment protocol and in one case (suture anchor fixation plus
      augmentation of the posterolateral corner) a special postoperative PCL
      rehabilitation protocol was used. Good clinical results with stable knee joints
      could be achieved in all cases. The minimally invasive dorsal approach for the
      treatment of bony avulsions of the PCL was demonstrated to be safe and simple
      with a low complication rate.

PMID- 23010886
TI  - [Minimally invasive osteosynthesis].

PMID- 23010882
TI  - Desvenlafaxine compared with placebo for treatment of menopausal vasomotor
      symptoms:  a 12-week, multicenter, parallel-group, randomized, double-blind,
      placebo-controlled efficacy trial.
AB  - OBJECTIVE: The aim of this study was to assess the 12-week efficacy of
      desvenlafaxine in treating moderate to severe vasomotor symptoms and the clinical
      relevance of improvements in postmenopausal women experiencing 50 or more
      moderate to severe hot flashes per week. METHODS: Participants were randomized to
      placebo or desvenlafaxine 100 mg/day in the 12-week efficacy substudy of a year
      long, multicenter, parallel-group, double-blind study. Coprimary outcomes were
      changes from baseline in the daily number and severity of hot flashes on weeks 4
      and 12. The percentage of women achieving the minimal clinically important
      difference (MCID) in the number of hot flashes on week 12 was determined.
      RESULTS: The efficacy substudy modified intent-to-treat population included 365
      women (desvenlafaxine, n = 184; placebo, n = 181). Desvenlafaxine 100 mg/day
      significantly reduced the number and severity of hot flashes versus placebo on
      week 4 (P < 0.001) and week 12 (P < 0.001). On week 12, desvenlafaxine reduced
      the number of moderate and severe hot flashes by 7.3 (62%) per day (placebo, -4.5
      [38%] per day) and the severity score by 0.59 (25%) per day (placebo, -0.28 [12%]
      per day). MCID-a reduction of 5.35 moderate and severe hot flashes per day-was
      achieved by 64% of desvenlafaxine-treated women (placebo, 41%; P < 0.001). In
      all, 17.2% (67/390) of participants discontinued, 10.0% (20/200) of participants
      taking desvenlafaxine and 3.7% (7/190) of participants taking placebo
      discontinued because of adverse events (P = 0.016), and 2.5% (5/200) of
      participants taking desvenlafaxine and 8.4% (16/190) of participants taking
      placebo discontinued because of lack of efficacy (P = 0.012). CONCLUSIONS:
      Postmenopausal women with moderate to severe hot flashes who are treated with
      desvenlafaxine achieve rapid symptom reduction that is clinically relevant based
      on MCID.

PMID- 23010887
TI  - [Certified continuing medical education in Operative Orthopadie und
      Traumatologie].

PMID- 23010889
TI  - Autoimmune manifestations in viral hepatitis.
AB  - Infections by the viruses responsible for hepatitis B, C and D are accompanied by
      a number of immunopathological manifestations. A link between infection and
      autoimmunity is particularly well documented for the hepatitis C virus.
      Immunopathological manifestations range from production of autoantibodies to
      overt autoimmune disease, including thyroiditis and autoimmune hepatitis, and to
      immune-complex-mediated disorders, including cryoglobulinaemia,
      glomerulonephritis and vasculitis. Several of these manifestations improve with
      successful antiviral treatment, directly incriminating the virus in their
      pathogenesis. Mechanisms considered responsible for hepatitis virus-related
      immunopathology, including molecular mimicry, impairment of regulatory T cells
      and activation of B lymphocytes, will be examined in this review.

PMID- 23010890
TI  - Hepatocellular carcinoma in chronic hepatitis C: from bench to bedside.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and seventh
      in women, accounting for 7 % of all cancers, and the third cause of cancer
      related death worldwide. Nearly 90 to 95 % of all HCC occur in the context of
      known and often preventable risk factors, such as chronic viral hepatitis,
      alcohol abuse, and metabolic disorders. Although several experimental lines of
      research support a direct role for hepatitis C virus (HCV) in cancer promotion,
      cirrhosis is the main risk factor for this tumor, whereas other factors like
      alcohol and tobacco smoking are clearly able to accelerate HCC development. For
      this reason, cirrhotic patients with chronic HCV infection are subjected to
      abdominal ultrasound surveillance every 6 months, aimed at an early diagnosis of
      HCC to allow curative treatment options. Current strategies to positively impact
      on HCC incidence rates in HCV patients include prevention of cirrhosis
      development by avoiding metabolic, pharmacological, or social factors associated
      with accelerated progression of liver disease, or through virus eradication by
      interferon-based treatments. Moreover, a successful antiviral treatment has the
      added benefit of positively impacting on the rate of HCC development also in
      patients who are already cirrhotic.

PMID- 23010891
TI  - Participation of protein kinase C in the activation of Nrf2 signaling by ischemic
      preconditioning in the isolated rabbit heart.
AB  - Activation of protein kinase C (PKC) is a critical intracellular signaling
      triggered by ischemic preconditioning (IPC), but the precise mechanisms
      underlying the actions of PKC in IPC-mediated cardioprotection remain unclear.
      Here, we investigated the role of PKC activation on the antioxidant activity by
      IPC in rabbit hearts. Isolated rabbit hearts were subjected to 60 min of global
      ischemia by cold cardioplegic arrest (4  degrees C) and 60 min of reperfusion (37
      degrees C). IPC was induced by three cycles of 2-min ischemia following 3 min of
      reperfusion (37  degrees C) before cardioplegic arrest. IPC resulted in a better
      recovery of mechanical function, increased tissue reduced glutathione-to-oxidized
      glutathione ratio (GSH/GSSG), superoxide dismutase and catalase content, and
      decreased tissue malondialdehyde (MDA) content compared to control hearts
      subjected to 60 min of cardioplegic ischemia and 60 min of reperfusion. IPC also
      significantly induced activation of nuclear factor erythroid 2-related factor 2
      (Nrf2) and the inductions of antioxidant genes heme oxygenase-1 (HO-1) and
      manganese superoxide dismutase (MnSOD). Injection of phorbol 12-myristate 13
      acetate, an activator of PKC, before cardioplegic ischemia induced translocation
      of PKC-delta and -epsilon isoforms to membrane fraction, nuclear accumulation of
      Nrf2, and conferred cardioprotection similar to IPC. Polymyxin B, an inhibitor of
      PKC, blocked the membrane translocation of PKC-delta and -epsilon during IPC,
      inhibited Nrf2 nuclear accumulation, and significantly diminished the IPC-induced
      cardioprotection when administrated before IPC. These results indicate that the
      activation of PKC induces the translocation of Nrf2 and the enhancement of
      endogenous antioxidant defenses in the IPC hearts and suggest that PKC may target
      Nrf2 to confer cardioprotection.

PMID- 23010892
TI  - Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC-PKC-CaMK II- and
      Janus kinase-dependent signaling pathway.
AB  - Serotonin (5-HT) is a hormone that has been implicated in the regulation of many
      physiological and pathological events. One of the most intriguing properties of
      this hormone is its ability to up-regulate mitosis. Moreover, 5-HT stimulates
      glucose uptake and up-regulates PFK activity through the 5-HT(2A) receptor,
      resulting in the phosphorylation of a tyrosine residue of PFK and the
      intracellular redistribution of PFK within skeletal muscle. The present study
      investigated some of the signaling intermediates involved in the effects of 5-HT
      on 6-phosphofructo-1-kinase (PFK) regulation from skeletal muscle using kinetic
      assessments, immunoprecipitation, and western blotting assays. Our results
      demonstrate that 5-HT stimulates PFK from skeletal muscle via phospholipase C
      (PLC). The activation of PLC in skeletal muscle leads to the recruitment of
      protein kinase C (PKC) and calmodulin and the stimulation of calmodulin kinase
      II, which associates with PFK upon 5-HT action. Alternatively, 5-HT loses its
      ability to up-regulate PFK activity when Janus kinase is inhibited, suggesting
      that 5-HT is able to control glycolytic flux in the skeletal muscle of mice by
      recruiting different pathways and controlling PFK activity.

PMID- 23010893
TI  - Inhibition of anti-apoptotic signals by Wortmannin induces apoptosis in the
      remote myocardium after LAD ligation: evidence for a protein kinase C-delta
      dependent pathway.
AB  - It has been shown that, in the remote myocardium after infarction (MI), protein
      kinase C (PKC) inhibition reduces apoptosis both by blocking proapoptotic
      pathways and by activating antiapoptotic signals including the Akt pathway.
      However, it was open if vice versa, blockade of antiapoptotic pathways may
      influence proapoptotic signals. To clarify this, the present study tested the
      effects of the PI3-kinase blocker Wortmannin on proapoptotic signals and on
      apoptosis execution in the remote myocardium after infarction. Rats were
      subjected to MI by LAD ligation in situ. Some were pre-treated with Wortmannin
      alone or in combination with the PKC inhibitor Chelerythrine. After 24 h, pro-
      and anti-apoptotic signals (caspase-3, PKC isoforms, p38-MAPK, p42/44-MAPK, Akt,
      Bad), and marker of apoptosis execution (TUNEL) were quantified in the myocardium
      remote from the infarction. Wortmannin treatment increased apoptosis in the
      remote myocardium both at baseline and after MI, together with an activation of
      the PKC-delta/p38-MAPK-pathway. PKC-epsilon and p42/44-MAPK were unaffected.
      Combined treatment with Wortmannin and Chelerythrine fully reversed the pro
      apoptotic effects of Wortmannin both at baseline and after MI. The PKC-delta-p38
      MAPK-pathway as a strong signal for apoptosis in the non-infarcted myocardium can
      be influenced by targeting the anti-apoptotic PI3-kinase pathway. This gives
      evidence of a bi-directional crosstalk of pro- and anti-apoptotic signals after
      infarction.

PMID- 23010894
TI  - Atmospheric influence on the distribution of organic pollutants in the
      Guadalquivir River estuary, SW Spain.
AB  - In the lower Guadalquivir river basin, a system stressed by a wide variety of
      anthropogenic activities, eight pesticides (four triazines, two chloroacetanilide
      herbicides, one organochlorine, and one organophosphorus insecticide); and four
      emerging pollutants (two personal care products, one organophosphorous flame
      retardant, and one xanthine alkaloid) were analyzed in river water during a 2
      year monitoring program, and after rain episodes. Samples were extracted using
      the solid phase extraction (SPE) technique prior to determination of compounds
      using gas chromatograph coupled to a mass spectrometer detector. Except for
      caffeine, recoveries were mostly above 80 %, while limits of detection and
      quantification were in the low nanograms per liter level (except for dimethoate).
      Terbuthylazine, simazine (triazine herbicides), and dimethoate (organophosphorus
      insecticide), present in agrochemicals, were predominant in the river water,
      although concentrations were below the quality standards established by the EU
      Water-Framework-Directive. A general trend to increase concentration was observed
      after rain events, in particular for pesticides, possibly as a consequence of
      surface runoff.

PMID- 23010895
TI  - Seasonal analysis of the generation and composition of solid waste: potential use
      -a case study.
AB  - Ensenada health officials lack pertinent information on the sustainable
      management of solid waste, as do health officials from other developing
      countries. The aims of this research are: (a) to quantify and analyze the
      household solid wastes generated in the city of Ensenada, Mexico, and (b) to
      project biogas production and estimate generation of electrical energy. The
      characterization study was conducted by socioeconomic stratification in two
      seasonal periods, and the biogas and electrical energy projections were performed
      using the version 2.0 Mexico Biogas Model. Per capita solid waste generation was
      0.779 +/- 0.019 kg per person per day within a 98 % confidence interval. Waste
      composition is composed mainly of food scraps at 36.25 %, followed by paper and
      cardboard at 21.85 %, plastic at 12.30 %, disposable diapers at 6.26 %, and
      textiles at 6.28 %. The maximum capacity for power generation is projected to be
      1.90 MW in 2019. Waste generated could be used as an intermediate in different
      processes such as recycling (41.04 %) and energy recovery (46.63 %). The
      electrical energy that could be obtained using the biogas generated at the
      Ensenada sanitary landfill would provide roughly 60 % of the energy needed for
      street lighting.

PMID- 23010896
TI  - Pneumothorax as a complication of ultrasound-guided interscalene block for
      shoulder surgery.

PMID- 23010897
TI  - Anaesthesia and orphan disease:  management of cardiac and perioperative risks in
      a patient with Emery-Dreifuss muscular dystrophy.

PMID- 23010898
TI  - Anaesthesia for renal transplant surgery:  an update.
AB  - Although the overall outcome of patients undergoing renal transplant surgery has
      improved in recent years, delayed graft function and myocardial infarction remain
      common and severe postoperative complications. This review article provides an
      update on anaesthesia for renal transplant surgery in order to optimise
      perioperative therapy and improve the outcome of these patients. In particular,
      the characteristics of this high-risk population and the recommendations for
      preoperative 'work-up' are summarised. Care for the living donor, commonly used
      drugs and their potential nephrotoxic properties are discussed. Finally, the
      current knowledge about volume therapy, optimised haemodynamic management and
      postoperative care is described.

PMID- 23010899
TI  - 5-Hydroxy ericamycin, a new anthraquinone with potent antimicrobial activity.

PMID- 23010900
TI  - Bioactive anthraquinone dimers from the leafhopper pathogenic fungus Torrubiella
      sp. BCC 28517.
AB  - Torrubiellins A (1) and B (2), two new dimeric anthraquinones were isolated from
      the leafhopper pathogenic fungus Torrubiella sp. BCC 28517. The structures of the
      new compounds were elucidated by analyses of the NMR spectroscopic and mass
      spectrometry data. Torrubiellin B (2) exhibited broad range of biological
      activities.

PMID- 23010901
TI  - Diversity in the antimicrobial susceptibility patterns of methicillin-resistant
      Staphylococcus aureus clones.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is well known for its
      epidemicity, with the emergence of new clones on a daily basis. Diversity in the
      clonal types of MRSA challenges the success of treatment, as different clones
      respond to different sets of antibiotics. However, the antibiotic susceptibility
      among the isolates within the same clones is largely unexplored. In a previous
      study on MRSA epidemiology in Malaysia, we identified six major clonal complexes
      (ST-239-CC8, ST-1-CC1, ST-188-CC1, ST-22-CC22, ST-7-CC7 and ST-1283-CC8). In the
      present study, we investigated the antibiotic susceptibility patterns of isolates
      of different clones. Three hundred and eighty-nine MRSA isolates were subjected
      to the disc diffusion test, oxacillin minimum inhibitory concentration (MIC)
      determination and assessment of the distribution of macrolide, lincosamide and
      streptogramin B (MLS(B)) resistance genes. Thirty-six different antibiotic
      profiles were observed: 30 (83.3 %) among ST-239, 2 (5.6 %) among ST-1283 and 1
      (2.8 %) each for ST-1, ST-7, ST-22 and ST-188. All ST-239 (362, 9 %) isolates
      were multiple drug-resistant (MDR; resistant to more than three classes of
      antibiotics) and had oxacillin MICs >256 mg/l. Among the 385 clindamycin
      resistant isolates, 375 (96.4 %) illustrated inducible resistance (D-zone
      positive), while 10 (2.6 %) showed constitutive resistance. The vast majority of
      the macrolide-resistant isolates carried the ermA gene (95.1 %), followed by ermC
      (12.9 %). Diversity in the antibiotic susceptibilities of isolates within the
      clones emphasises the need for continuous surveillance of MDR strains to
      prescribe the correct antibiotic rather than empirical treatment. This will
      likely reduce the emergence of new endemic or epidemic resistant MRSA clones.

PMID- 23010903
TI  - Unnecessary repeat Clostridium difficile PCR testing in hospitalized adults with
      C. difficile-negative diarrhea.
AB  - The aim of this study was to determine the extent and associated costs of repeat
      Clostridium difficile stool polymerase chain reaction (PCR) assays in patients
      with initially negative PCRs. C. difficile stool PCRs were done on adult
      hospitalized patients with diarrhea. The number/time course of repeat PCRs on
      initially negative PCR patients was determined. Of 5,027 C. difficile stool PCRs,
      814 (16.2 %) were positive and 4,213 (83.8 %) were negative. Ninety-seven of the
      initially PCR-negative patients had >2 repeat tests 1-59 days after the initial
      negative stool PCR. Repeat negative PCR testing rarely resulted in a subsequent
      positive result (0.05 %). The unnecessary costs of 97 repeat PCRs was $32,658.00.
      Many of these patients were originally given empiric oral anti-C. difficile
      therapy, in spite of repeatedly negative PCRs.

PMID- 23010902
TI  - Utility of two biomarkers for directing care among patients with non-severe
      community-acquired pneumonia.
AB  - The aim of the present study is to evaluate the usefulness of two biomarkers
      procalcitonin (PCT) and C-reactive protein (CRP)-in addition to the CURB-65 score
      for assessing the site of care and the etiology of non-severe community-acquired
      pneumonia (CAP). We conducted a prospective observational study from April 1,
      2006, to June 30, 2007, in a single teaching hospital in northern Spain among
      patients with non-severe CAP. In addition to collecting data needed to determine
      the CURB-65 score, microbial cultures were taken and levels of PCT and CRP were
      measured. We compared the prognostic accuracy of these biomarkers with the CURB
      65 score to predict hospitalization and microbial etiology using receiver
      operating characteristic (ROC) curves. A total of 344 patients with non-severe
      CAP were enrolled; 73 were admitted to the hospital and 271 were treated on an
      outpatient basis. An etiologic diagnostic was made for 44 %, with atypical
      pathogens predominating. Levels of PCT and CRP increased with increasing CURB-65
      scores. Patients admitted to the hospital had higher PCT and CRP levels than
      outpatients (p < 0.001). For predicting hospitalization, PCT had a better area
      under the ROC curve (AUC) (0.81) than the CURB-65 score alone (0.77). For PCT
      plus the CURB-65 score, the AUC increased significantly from 0.77 to 0.83. In
      patients with bacterial CAP, the biomarker levels were significantly higher than
      among patients with atypical or viral etiology (p < 0.001). PCT with a cut-off
      point of 0.15 ng/mL was the best predictor for bacterial etiology and for select
      patients eligible for outpatient care. In conclusion, levels of PCT and CRP
      positively correlate with increasing severity of CAP and may have a role in
      predicting both patients who can safely receive outpatient care and the microbial
      etiology in patients with low CURB-65 scores.

PMID- 23010904
TI  - Evaluation of Meridian TRU Legionella(r), a new rapid test for detection of
      Legionella pneumophila serogroup 1 antigen in urine samples.
AB  - We evaluated the ability of a new antigen test (TRU Legionella(r) assay, Meridian
      Bioscience, Cincinnati, OH, USA) to detect Legionella pneumophila serogroup 1
      antigen in urine. The results were compared with those obtained with the Binax
      NOW(r) urinary antigen test (Binax, Portland, ME, USA). The sensitivities and
      specificities were 73 % [95 % confidence interval (CI), 65 to 81 %] and 100 %,
      respectively, for the Meridian TRU Legionella test and 77 % (95 % CI, 68 to 84 %)
      and 100 %, respectively, for the Binax NOW urinary antigen test. The sensitivity
      of the Meridian TRU Legionella test increased to 81 % if tests were re-examined
      after 60 min of incubation. Prolonged incubation did not affect the specificity.
      We conclude that both assays evaluated have similar performance characteristics
      and are suitable for the rapid diagnosis of Legionnaires' disease.

PMID- 23010905
TI  - Targeted screening as a tool for the early detection of chronic Q fever patients
      after a large outbreak.
AB  - In the aftermath of the Dutch Q fever outbreak, an increasing number of patients
      are being diagnosed with chronic Q fever. Most of these patients are unaware of
      being infected with Coxiella burnetii, the causative agent of Q fever. To find
      patients in an earlier, asymptomatic stage, a targeted screening strategy (TSS)
      for patients with risk factors for chronic Q fever was started in the southeast
      region of Noord-Brabant. In total, 763 patients were tested using an IgG phase II
      indirect fluorescent antibody test (IFAT), of which 52 (7 %) patients tested
      positive. Ten of these 52 patients displayed a chronic Q fever serological
      profile. All of these 10 patients had a heart valve(s) or (endo-)vascular
      prosthesis. All except one were asymptomatic. Suggestive signs for chronic
      infections on positron emission tomography-computed tomography (PET-CT) were
      demonstrated in 5 (50 %) of these patients. Forty-two out of the 52 patients with
      a positive screening test showed a past Q fever serological profile. After a year
      of follow-up (every 3 months), none of these patients showed elevation of
      antibody titres and no new chronic Q fever patients were found in this group. A
      targeted screening programme is a useful instrument for detecting patients at
      risk of developing chronic Q fever.

PMID- 23010906
TI  - Radiological age estimation: based on third molar mineralization and eruption in
      Turkish children and young adults.
AB  - Radiographic evaluation of mineralization and eruption stages of third molars
      using dental panoramic radiographies can be an efficient tool for chronological
      age estimation in both forensic sciences and legal medicine. The third molar
      tooth is utilized for dental age estimation about the age span of 15-23 years
      because it represents the only tooth still in development. The aim of this study
      is to obtain and analyze data regarding third molar development and eruption in
      Turkish population for dental age estimation. A total of 744 dental panoramic
      radiographies of 394 female and 350 male subjects aged between 8 and 22 years
      were examined. Third molar development was determined according to the Nolla
      classification system, and eruption was assessed relative to the alveolar bone
      level. Mandibular and maxillary third molars were generally found at similar
      stages of development on both sides. Nolla stage 6 (completed crown
      calcification) was reached at around the age of 15 in both maxillary and
      mandibular third molars in both sexes. Alveolar emergence was at around the age
      of 16 in males and around age of 17 in females. Although third molars' eruption
      shows greater variability than development of third molars, data which were
      obtained from this study about eruption of these teeth can be supportive to
      development data for age estimation.

PMID- 23010907
TI  - Stability of endogenous reference genes in postmortem human brains for
      normalization of quantitative real-time PCR data: comprehensive evaluation using
      geNorm, NormFinder, and BestKeeper.
AB  - In forensic molecular pathology, quantitative real-time polymerase chain reaction
      (RT-qPCR) provides a rapid and sensitive method to investigate functional changes
      in the death process. Accurate and reliable relative RT-qPCR requires ideal
      amplification efficiencies of target and reference genes. However, the
      amplification efficiency, changing during PCR, may be overestimated by the
      traditional standard curve method. No single gene meets the criteria of an ideal
      endogenous reference. Therefore, it is necessary to select suitable reference
      genes for specific requirements. The present study evaluated 32 potential
      reference genes in the human brain of 15 forensic autopsy cases using three
      different statistical algorithms, geNorm, NormFinder, and BestKeeper. On RT-qPCR
      data analyses using a completely objective and noise-resistant algorithm (Real
      time PCR Miner), 24 genes met standard efficiency criteria. Validation of their
      stability and suitability as reference genes using geNorm suggested IPO8 and
      POLR2A as the most stable ones, and NormFinder indicated that IPO8 and POP4 had
      the highest expression stabilities, while BestKeeper highlighted ABL1 and ELF1 as
      reference genes with the least overall variation. Combining these three
      algorithms suggested the genes IPO8, POLR2A, and PES1 as stable endogenous
      references in RT-qPCR analysis of human brain samples, with YWHAZ, PPIA, HPRT1,
      and TBP being the least stable ones. These findings are inconsistent with those
      of previous studies. Moreover, the relative stability of target and reference
      genes remains unknown. These observations suggest that suitable reference genes
      should be selected on the basis of specific requirements, experiment conditions,
      and the characteristics of target genes in practical applications.

PMID- 23010908
TI  - Micro-CT features of intermediate gunshot wounds severely damaged by fire.
AB  - Incineration or extensive burning of the body, causing changes in the content and
      distribution of fluids, fixation and shrinking processes of tissues, can alter
      the typical macroscopic and microscopic characteristics of firearm wounds,
      hampering or at least complicating the reconstruction of gunshot fatalities. The
      present study aims at evaluating the potential role of micro-computed tomography
      (micro-CT) for detecting and quantifying gunshot residue (GSR) particles in
      experimentally produced intermediate-range gunshot wounds severely damaged by
      fire. Eighteen experimental shootings were performed on 18 sections of human
      calves surgically amputated for medical reasons at three different firing
      distances (5, 15 and 30 cm). Six stab wounds produced with an ice pick were used
      as controls. Each calf section underwent a charring cycle, being placed in a wood
      burning stove for 4 min at a temperature of 400  degrees C. At visual inspection,
      the charred entrance wounds could not be differentiated from the exit lesions and
      the stab wounds. On the contrary, micro-CT analysis showed the presence of GSR
      particles in all burnt entrance gunshot wounds, while GSR was absent in the exit
      and stab wounds. The GSR deposits of the firearm lesions inflicted at very close
      distance (5 cm) were mainly constituted of huge particles (diameter >150 MUm)
      with an irregular shape and well-delineated edges; at greater distances (15 and
      30 cm), agglomerates of tiny radiopaque particles scattered in the epidermis and
      dermis layers were evident. Statistical analysis demonstrated that also in
      charred firearm wounds the amount of GSR roughly correlates with the distance
      from which the gun was fired. The obtained results suggest that micro-CT analysis
      can be a valid screening tool for identifying entrance gunshot wounds and for
      differentiating firearm wounds from sharp-force injuries in bodies severely
      damaged by fire.

PMID- 23010910
TI  - Iminium ion catalysis: the enantioselective Friedel-Crafts alkylation
      acetalization cascade of naphthols with alpha,beta-unsaturated cyclic ketones.
AB  - The first enantioselective Friedel-Crafts alkylation-acetalization-cascade of
      naphthols with alpha,beta-unsaturated cyclic ketones and 1H-inden-1-ones was
      realized. 9-Amino(9-deoxy)epi-quinine A was the catalyst of choice for the
      realization of polycyclic structures with high enantiocontrol.

PMID- 23010909
TI  - Studies of bacterial aerotaxis in a microfluidic device.
AB  - Aerotaxis, the directional motion of bacteria in gradients of oxygen, was
      discovered in the late 19th century and has since been reported in a variety of
      bacterial species. Nevertheless, quantitative studies of aerotaxis have been
      complicated by the lack of tools for generation of stable gradients of oxygen
      concentration, [O(2)]. Here we report a series of experiments on aerotaxis of
      Escherichia coli in a specially built experimental setup consisting of a computer
      controlled gas mixer and a two-layer microfluidic device made of
      polydimethylsiloxane (PDMS). The setup enables generation of a variety of stable
      linear profiles of [O(2)] across a long gradient channel, with characteristic
      [O(2)] ranging from aerobic to microaerobic conditions. A suspension of E. coli
      cells is perfused through the gradient channel at a low speed, allowing cells
      enough time to explore the [O(2)] gradient, and the distribution of cells across
      the gradient channel is analyzed near the channel outlet at a throughput of
      >10(5) cells per hour. Aerotaxis experiments are performed in [O(2)] gradients
      with identical logarithmic slopes and varying mean concentrations, as well as in
      gradients with identical mean concentrations and varying slopes. Experiments in
      gradients with [O(2)] ranging from 0 to ~11.5% indicate that, in contrast to some
      previous reports, E. coli cells do not congregate at some intermediate level of
      [O(2)], but rather prefer the highest accessible [O(2)]. The presented technology
      can be applied to studies of aerotaxis of other aerobic and microaerobic
      bacteria.

PMID- 23010911
TI  - Heart rate asymmetry follows the inspiration/expiration ratio in healthy
      volunteers.
AB  - Heart rate asymmetry (HRA) quantifies the uneven distribution of points above and
      below the identity-line in a Poincare plot of RR-intervals. The authors
      investigated if HRA could be influenced by the inspiration/expiration ratio.
      Healthy volunteers (n = 18) were studied in the supine position at 4.5 s
      metronome breathing. ECG and breathing signals were recorded for 360 s at each
      breathing pattern: inspiration controlled, inspiration/expiration controlled
      (1:2, 1:1, 2:1 ratio), inspiration controlled again. Time domain, frequency
      domain and Poincare plot heart rate variability (HRV) analysis with Porta's and
      Guzik's indices were performed on 300 s tachograms. There were no statistically
      significant differences in time domain, frequency domain and standard Poincare
      plot parameters during the various breathing patterns, whereas Porta's and
      Guzik's indices significantly rose at 1:1 and 2:1 compared to physiological 1:2
      breathing. There were no significant differences in the HRA parameters between
      the first and the last runs. In our population the inspiration/expiration ratio
      significantly influenced HRA, but not standard HRV parameters. Positive
      correlation of Guzik's and Porta's index reflects reciprocal changes of the
      number of points and their dispersion in the accelerating and decelerating sets
      of RR-intervals. HRA-analysis can be a promising method for investigating
      cardiovascular regulation/health particularly with further spreading of wearable
      monitors.

PMID- 23010912
TI  - Electron states in a silicon nanowire in the presence of surface potential and
      field.
AB  - In this paper, the energy states of electrons in a silicon nanowire are
      analytically calculated in the presence of a surface potential and an electric
      field, as in a nanowire field-effect transistor. The calculations are done for
      both partial and complete volume inversion and accumulation biasing conditions.
      Computations are performed for the <100> and <110> orientations of the silicon
      nanowire. The results show the effects of the surface potential, the electric
      field and the transverse dimensions of the nanowire on the electron energies and
      wavefunctions. Depending on the combinations of the surface potential and
      electric field, the energy level can increase, decrease or remain constant as the
      thickness of the nanowire increases. It is also observed that higher surface
      potentials can significantly change the energy states due to the increase of
      volume inversion/accumulation.

PMID- 23010913
TI  - Beyond reproach.

PMID- 23010915
TI  - Twenty years of donnerwheeler: what we've learned.

PMID- 23010916
TI  - All hands on deck!

PMID- 23010917
TI  - Who will lead nursing into the future?
AB  - Recent research reveals a need for improved leadership capabilities among nurses,
      from the front-line nurse to those in management capacities. This "op-ed" piece
      is a discussion arising from the results of a study examining two groups of high
      school students: one participating in a leadership training program and one not
      participating. With their responses, these students demonstrated a stereotypical
      view of the work of nurses and were not interested in pursuing a career in
      nursing. They also didn't see nursing as a career in which to practise their
      leadership abilities. We raise questions about our ability to meet the goals of
      the Canadian Nursing Association as set out in Toward 2020 if we, in the nursing
      profession, are not successful in attracting students who understand the
      complexities of nursing practice and have a desire and the ability to help
      advance the profession in Canada. Recommendations for further research are
      presented.

PMID- 23010918
TI  - Using quality indicators to evaluate the effect of implementing an enhanced
      collaborative care model among a community, primary healthcare practice
      population.
AB  - Over the past decade, Nova Scotia has been making important changes to strengthen
      its primary healthcare (PHC) system. Here we present the results from an
      observational, retrospective study evaluating the effect of an enhanced
      collaborative care model, which included team building and the addition of a
      nurse practitioner (NP) to the team, on the quality of healthcare delivery among
      a community, PHC population. To guide the evaluation, we used a broad range of
      national and provincially identified clinical quality-of-care indicators
      targeting a wide range of preventive and chronic disease management care
      (targeting process of care, and immediate and secondary outcomes). A total of 392
      patient charts were audited (197 pre-period; 195 post-period). Patients included
      the full spectrum of the practice population - the young, the old, those with
      chronic conditions and others without. Results support the increasing body of
      evidence, which indicates improved chronic disease management among patients with
      targeted chronic conditions, particularly patients diagnosed with diabetes, who
      receive care through a collaborative practice where a NP is part of the team. In
      addition, these results also demonstrate the beginning of better preventive care
      among all patients.

PMID- 23010919
TI  - An exploration of patient satisfaction in a nurse practitioner-led clinic.
AB  - A unique and innovative model of primary healthcare (PHC) delivery began at the
      Sudbury District Nurse Practitioner Clinics (SDNPC) in 2007. Significant growth
      and development has taken place since the opening of this new model of PHC
      delivery. Now that SDNPC is operating at full capacity, an evaluation was
      warranted of patient experiences with clinic services and the level of overall
      patient satisfaction. A survey of clinic patients was conducted in the spring of
      2011. Results demonstrated high satisfaction with clinic services. Some areas
      were identified for review, including the level of accessibility to same-day
      appointments and rationale for patient use of walk-in clinics and emergency
      department care. One of the strengths and benefits of this model of NP care was
      demonstrated in this evaluation, whereby a majority of patients identified that
      they had received counselling about a lifestyle issue and, of those patients,
      most reported a resulting positive health-related behavioural change. Ongoing
      comprehensive evaluation is important to ensure that services are efficient and
      directed to optimal patient health outcomes.

PMID- 23010920
TI  - Career advancement and educational opportunities: experiences and perceptions of
      internationally educated nurses.
AB  - The number of internationally educated nurses is increasing in the Canadian
      workforce. Recruitment of internationally educated nurses is often seen as a
      solution to ongoing nursing shortages. However, international recruitment needs
      to be accompanied by strategies to ensure long-term retention. One of the
      criteria for successful retention is the availability and accessibility of career
      advancement and educational opportunities. Little research exists on the
      opportunities for career advancement and education for internationally educated
      nurses in Canada. This interpretive descriptive study was conducted to look at
      the perceptions of internationally educated nurses regarding career advancement
      and educational opportunities in Alberta, Canada. Eleven internationally educated
      nurses, working as registered nurses in Alberta, were interviewed using semi
      structured interviews. Five themes were identified: motherhood as a priority,
      communication and cultural challenges, process of skill recognition, perceptions
      of opportunity and need for mentorship.

PMID- 23010921
TI  - Metal oxidation kinetics and the transition from thin to thick films.
AB  - We report an investigation of growth kinetics and transition from thin to thick
      films during metal oxidation. In the thin film limit (<20 nm), Cabrera and Mott's
      theory is usually adopted by explicitly considering ionic drift through the oxide
      in response to electric fields, where the growth kinetics follow an inverse
      logarithmic law log(dl/dt) is proportional to 1/l. It is generally accepted that
      Wagner's theory, involving self-diffusion, is valid only in the limit of thick
      film regime (>1 MUm) and leads to parabolic growth kinetics dl/dt is proportional
      to 1/l, where l is the oxide film thickness. Theory presented here unifies the
      two models and provides a complete description of oxidation including the
      transition from thin to thick film. The range of validity of Cabrera and Mott's
      theory and Wagner's theory can be well defined in terms of the Debye-Huckel
      screening length. The transition from drift-dominated ionic transport for thin
      film to diffusion-dominated transport for thick film is found to strictly follow
      the direct logarithmic law log(dl/dt) is proportional to -l that is frequently
      observed in many experiments.

PMID- 23010922
TI  - Dynamics of the leading process, nucleus, and Golgi apparatus of migrating
      cortical interneurons in living mouse embryos.
AB  - Precisely arranged cytoarchitectures such as layers and nuclei depend on neuronal
      migration, of which many in vitro studies have revealed the mode and underlying
      mechanisms. However, how neuronal migration is achieved in vivo remains unknown.
      Here we established an imaging system that allows direct visualization of
      cortical interneuron migration in living mouse embryos. We found that during
      nucleokinesis, translocation of the Golgi apparatus either precedes or occurs in
      parallel to that of the nucleus, suggesting the existence of both a
      Golgi/centrosome-dependent and -independent mechanism of nucleokinesis. Changes
      in migratory direction occur when the nucleus enters one of the leading process
      branches, which is accompanied by the retraction of other branches. The nucleus
      occasionally swings between two branches before translocating into one of them,
      the occurrence of which is most often preceded by Golgi apparatus translocation
      into that branch. These in vivo observations provide important insight into the
      mechanisms of neuronal migration and demonstrate the usefulness of our system for
      studying dynamic events in living animals.

PMID- 23010923
TI  - 3D imaging and mechanical modeling of helical buckling in Medicago truncatula
      plant roots.
AB  - We study the primary root growth of wild-type Medicago truncatula plants in
      heterogeneous environments using 3D time-lapse imaging. The growth medium is a
      transparent hydrogel consisting of a stiff lower layer and a compliant upper
      layer. We find that the roots deform into a helical shape just above the gel
      layer interface before penetrating into the lower layer. This geometry is
      interpreted as a combination of growth-induced mechanical buckling modulated by
      the growth medium and a simultaneous twisting near the root tip. We study the
      helical morphology as the modulus of the upper gel layer is varied and
      demonstrate that the size of the deformation varies with gel stiffness as
      expected by a mathematical model based on the theory of buckled rods. Moreover,
      we show that plant-to-plant variations can be accounted for by biomechanically
      plausible values of the model parameters.

PMID- 23010924
TI  - HIV-1 Gag protein can sense the cholesterol and acyl chain environment in model
      membranes.
AB  - Membrane binding of the HIV-1 group-specific antigen (Gag) structural protein, a
      critical step in viral assembly at the plasma membrane, is mediated by the
      myristoylated, highly basic matrix (MA) domain, which interacts with negatively
      charged lipids in the inner leaflet. According to a popular model, virus
      particles bud from membrane rafts, microdomains enriched in cholesterol and high
      melting phospholipids with higher order than found outside rafts. How Gag might
      recognize membrane rafts, if they exist in the inner leaflet, is unknown. Using a
      liposome flotation assay with proteins translated in vitro, we investigated
      whether Gag can sense the composition of the hydrophobic part of the bilayer, by
      fixing lipid head group composition and varying hydrophobic properties. In
      liposomes composed solely of phosphatidylserine and phosphatidylcholine, and with
      the same overall membrane negative charge, Gag strongly preferred lipids with
      both acyl chains unsaturated over those with only one chain unsaturated. Adding
      cholesterol increased Gag binding and led to closer packing of phospholipids.
      However, higher membrane order, as measured by electron spin resonance, was not
      correlated with increased Gag binding. Gag proteins from two other retroviruses
      gave similar results. These liposome binding preferences were qualitatively
      recapitulated by purified myristoylated HIV-1 MA. Phosphatidylinositol 4,5
      bisphosphate and cholesterol enhanced binding in an additive manner. Taken
      together, these results show that Gag is sensitive both to the acyl chains of
      phosphatidylserine and to cholesterol concentration and other details of the
      membrane environment. These observations may help explain how retroviruses
      acquire a raft-like lipid composition.

PMID- 23010925
TI  - Building microscopic soccer balls with evaporating colloidal fakir drops.
AB  - Evaporation-driven particle self-assembly can be used to generate three
      dimensional microstructures. We present a unique method to create colloidal
      microstructures in which we can control the amount of particles and their packing
      fraction. To this end, we evaporate colloidal dispersion droplets on a special
      type of superhydrophobic microstructured surface, on which the droplet remains in
      Cassie-Baxter state during the entire evaporative process. The remainders of the
      droplet consist of a massive spherical cluster of the microspheres, with
      diameters ranging from a few tens up to several hundreds of microns. We present
      scaling arguments to show how the final particle packing fraction of these balls
      depends on the dynamics of the droplet evaporation, particle size, and number of
      particles in the system.

PMID- 23010926
TI  - Long range order and two-fluid behavior in heavy electron materials.
AB  - The heavy electron Kondo liquid is an emergent state of condensed matter that
      displays universal behavior independent of material details. Properties of the
      heavy electron liquid are best probed by NMR Knight shift measurements, which
      provide a direct measure of the behavior of the heavy electron liquid that
      emerges below the Kondo lattice coherence temperature as the lattice of local
      moments hybridizes with the background conduction electrons. Because the transfer
      of spectral weight between the localized and itinerant electronic degrees of
      freedom is gradual, the Kondo liquid typically coexists with the local moment
      component until the material orders at low temperatures. The two-fluid formula
      captures this behavior in a broad range of materials in the paramagnetic state.
      In order to investigate two-fluid behavior and the onset and physical origin of
      different long range ordered ground states in heavy electron materials, we have
      extended Knight shift measurements to URu(2)Si(2), CeIrIn(5), and CeRhIn(5). In
      CeRhIn(5) we find that the antiferromagnetic order is preceded by a
      relocalization of the Kondo liquid, providing independent evidence for a local
      moment origin of antiferromagnetism. In URu(2)Si(2) the hidden order is shown to
      emerge directly from the Kondo liquid and so is not associated with local moment
      physics. Our results imply that the nature of the ground state is strongly
      coupled with the hybridization in the Kondo lattice in agreement with phase
      diagram proposed by Yang and Pines.

PMID- 23010927
TI  - Conserved small protein associates with the multidrug efflux pump AcrB and
      differentially affects antibiotic resistance.
AB  - The AcrAB-TolC multidrug efflux pump confers resistance to a wide variety of
      antibiotics and other compounds in Escherichia coli. Here we show that AcrZ
      (formerly named YbhT), a 49-amino-acid inner membrane protein, associates with
      the AcrAB-TolC complex. Co-purification of AcrZ with AcrB, in the absence of both
      AcrA and TolC, two-hybrid assays and suppressor mutations indicate that this
      interaction occurs through the inner membrane protein AcrB. The highly conserved
      acrZ gene is coregulated with acrAB through induction by the MarA, Rob, and SoxS
      transcription regulators. In addition, mutants lacking AcrZ are sensitive to
      many, but not all, of the antibiotics transported by AcrAB-TolC. This
      differential antibiotic sensitivity suggests that AcrZ may enhance the ability of
      the AcrAB-TolC pump to export certain classes of substrates.

PMID- 23010929
TI  - Statistical detection of systematic election irregularities.
AB  - Democratic societies are built around the principle of free and fair elections,
      and that each citizen's vote should count equally. National elections can be
      regarded as large-scale social experiments, where people are grouped into usually
      large numbers of electoral districts and vote according to their preferences. The
      large number of samples implies statistical consequences for the polling results,
      which can be used to identify election irregularities. Using a suitable data
      representation, we find that vote distributions of elections with alleged fraud
      show a kurtosis substantially exceeding the kurtosis of normal elections,
      depending on the level of data aggregation. As an example, we show that reported
      irregularities in recent Russian elections are, indeed, well-explained by
      systematic ballot stuffing. We develop a parametric model quantifying the extent
      to which fraudulent mechanisms are present. We formulate a parametric test
      detecting these statistical properties in election results. Remarkably, this
      technique produces robust outcomes with respect to the resolution of the data and
      therefore, allows for cross-country comparisons.

PMID- 23010928
TI  - Structural and functional insights into alphavirus polyprotein processing and
      pathogenesis.
AB  - Alphaviruses, a group of positive-sense RNA viruses, are globally distributed
      arboviruses capable of causing rash, arthritis, encephalitis, and death in
      humans. The viral replication machinery consists of four nonstructural proteins
      (nsP1-4) produced as a single polyprotein. Processing of the polyprotein occurs
      in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA
      template use during genome replication. Here, we report the structure of P23 in a
      precleavage form. The proteins form an extensive interface and nsP3 creates a
      ring structure that encircles nsP2. The P2/3 cleavage site is located at the base
      of a narrow cleft and is not readily accessible, suggesting a highly regulated
      cleavage. The nsP2 protease active site is over 40 A away from the P2/3 cleavage
      site, supporting a trans cleavage mechanism. nsP3 contains a previously
      uncharacterized protein fold with a zinc-coordination site. Known mutations in
      nsP2 that result in formation of noncytopathic viruses or a temperature sensitive
      phenotype cluster at the nsP2/nsP3 interface. Structure-based mutations in nsP3
      opposite the location of the nsP2 noncytopathic mutations prevent efficient
      cleavage of P23, affect RNA infectivity, and alter viral RNA production levels,
      highlighting the importance of the nsP2/nsP3 interaction in pathogenesis. A
      potential RNA-binding surface, spanning both nsP2 and nsP3, is proposed based on
      the location of ion-binding sites and adaptive mutations. These results offer
      unexpected insights into viral protein processing and pathogenesis that may be
      applicable to other polyprotein-encoding viruses such as HIV, hepatitis C virus
      (HCV), and Dengue virus.

PMID- 23010930
TI  - Structure of the floating water bridge and water in an electric field.
AB  - The floating water bridge phenomenon is a freestanding rope-shaped connection of
      pure liquid water, formed under the influence of a high potential difference
      (approximately 15 kV). Several recent spectroscopic, optical, and neutron
      scattering studies have suggested that the origin of the bridge is associated
      with the formation of anisotropic chains of water molecules in the liquid. In
      this work, high energy X-ray diffraction experiments have been performed on a
      series of floating water bridges as a function of applied voltage, bridge length,
      and position within the bridge. The two-dimensional X-ray scattering data showed
      no direction-dependence, indicating that the bulk water molecules do not exhibit
      any significant preferred orientation along the electric field. The only
      structural changes observed were those due to heating, and these effects were
      found to be the same as for bulk water. These X-ray scattering measurements are
      supported by molecular dynamics (MD) simulations which were performed under
      electric fields of 10(6) V/m and 10(9) V/m. Directional structure factor
      calculations were made from these simulations parallel and perpendicular to the E
      field. The 10(6) V/m model showed no significant directional-dependence
      (anisotropy) in the structure factors. The 10(9) V/m model however, contained
      molecules aligned by the E-field, and had significant structural anisotropy.

PMID- 23010931
TI  - Superstructure of the centromeric complex of TubZRC plasmid partitioning systems.
AB  - Bacterial plasmid partitioning systems segregate plasmids into each daughter
      cell. In the well-understood ParMRC plasmid partitioning system, adapter protein
      ParR binds to centromere parC, forming a helix around which the DNA is externally
      wrapped. This complex stabilizes the growth of a filament of actin-like ParM
      protein, which pushes the plasmids to the poles. The TubZRC plasmid partitioning
      system consists of two proteins, tubulin-like TubZ and TubR, and a DNA
      centromere, tubC, which perform analogous roles to those in ParMRC, despite being
      unrelated in sequence and structure. We have dissected in detail the binding
      sites that comprise Bacillus thuringiensis tubC, visualized the TubRC complex by
      electron microscopy, and determined a crystal structure of TubR bound to the tubC
      repeat. We show that the TubRC complex takes the form of a flexible DNA-protein
      filament, formed by lateral coating along the plasmid from tubC, the full length
      of which is required for the successful in vitro stabilization of TubZ filaments.
      We also show that TubR from Bacillus megaterium forms a helical superstructure
      resembling that of ParR. We suggest that the TubRC DNA-protein filament may bind
      to, and stabilize, the TubZ filament by forming such a ring-like structure around
      it. The helical superstructure of this TubRC may indicate convergent evolution
      between the actin-containing ParMRC and tubulin-containing TubZRC systems.

PMID- 23010932
TI  - Uranium extremophily is an adaptive, rather than intrinsic, feature for extremely
      thermoacidophilic Metallosphaera species.
AB  - Thermoacidophilic archaea are found in heavy metal-rich environments, and, in
      some cases, these microorganisms are causative agents of metal mobilization
      through cellular processes related to their bioenergetics. Given the nature of
      their habitats, these microorganisms must deal with the potentially toxic effect
      of heavy metals. Here, we show that two thermoacidophilic Metallosphaera species
      with nearly identical (99.99%) genomes differed significantly in their
      sensitivity and reactivity to uranium (U). Metallosphaera prunae, isolated from a
      smoldering heap on a uranium mine in Thuringen, Germany, could be viewed as a
      "spontaneous mutant" of Metallosphaera sedula, an isolate from Pisciarelli
      Solfatara near Naples. Metallosphaera prunae tolerated triuranium octaoxide
      (U(3)O(8)) and soluble uranium [U(VI)] to a much greater extent than M. sedula.
      Within 15 min following exposure to "U(VI) shock," M. sedula, and not M. prunae,
      exhibited transcriptomic features associated with severe stress response.
      Furthermore, within 15 min post-U(VI) shock, M. prunae, and not M. sedula, showed
      evidence of substantial degradation of cellular RNA, suggesting that
      transcriptional and translational processes were aborted as a dynamic mechanism
      for resisting U toxicity; by 60 min post-U(VI) shock, RNA integrity in M. prunae
      recovered, and known modes for heavy metal resistance were activated. In
      addition, M. sedula rapidly oxidized solid U(3)O(8) to soluble U(VI) for
      bioenergetic purposes, a chemolithoautotrophic feature not previously reported.
      M. prunae, however, did not solubilize solid U(3)O(8) to any significant extent,
      thereby not exacerbating U(VI) toxicity. These results point to uranium
      extremophily as an adaptive, rather than intrinsic, feature for Metallosphaera
      species, driven by environmental factors.

PMID- 23010933
TI  - Frequency-invariant temporal ordering of interneuronal discharges during
      hippocampal oscillations in awake mice.
AB  - Endogenous brain rhythms occurring at various frequencies and associated with
      distinct behavioral states provide multiscale temporal windows that enable cells
      to time their spiking activity with high precision, which is thought to be
      important for the coding of information in neuronal circuits. However, although
      the selective timing of GABAergic inputs to specific spatial domains of principal
      cells are known to play key roles in network oscillations, the in vivo firing
      patterns of distinct hippocampal interneurons in awake animals are not known.
      Here we used a combination of juxtacellular labeling techniques with recordings
      from anesthesia-free, head-fixed mice running or resting on a spherical treadmill
      to study the oscillation-dependent discharges by two major interneuronal
      subtypes, the perisomatically projecting parvalbumin-positive basket cells
      (PVBCs) and distal dendritically projecting oriens lacunosum moleculare (OLM)
      cells. Recordings of the spiking activity of post hoc-identified CA1 interneurons
      during theta (5-10 Hz), gamma (25-90Hz), epsilon ("high-gamma"; 90-130 Hz), and
      ripple (130-200 Hz) oscillations revealed both cell type- and behavioral state
      dependent entrainments of PVBC and OLM cell discharges in awake mice. Our results
      in awake mice differed in several respects from previous data on interneuronal
      discharge patterns in anesthetized animals. In addition, our results demonstrate
      a form of frequency-invariant, cell type-specific temporal ordering of inhibitory
      inputs in which PVBC-derived perisomatic inhibition is followed by OLM cell
      generated distal dendritic inhibition during each of the network oscillation
      bands studied, spanning more than an order of magnitude in frequencies.

PMID- 23010934
TI  - Region-specific changes in activities of cell death-related proteases and nitric
      oxide metabolism in rat brain in a chronic unpredictable stress model.
AB  - Effects of a chronic combined unpredictable stress on activities of two cell
      death-related proteases, calpain and cathepsin B, were studied along with indices
      of nitrergic system in rat brain structures. Male Wistar rats were subjected to a
      2-week-long combined stress (combination of unpaired flash light and moderate
      footshock associated with a white noise session). Stress resulted in a
      significant loss in the body and thymus weight and increased defecation in the
      open field test, though neither motor and exploratory activity, nor plasma
      corticosterone differed from the respective control levels. Decreased calpain
      activity and increased cathepsin B activity were demonstrated in the hippocampus
      of stressed rats (previously we have shown that caspase-3 activity was
      significantly suppressed in the brain of rats subjected to same type of stress).
      A significant reduction in the number of NOS-containing neurons was accompanied
      by a chronic stressinduced decline in NOS activity in the neocortex. Similar
      changes were observed in the hippocampus. However, levels of NO metabolites were
      elevated in both structures. Thus, stress-induced structural modifications in the
      brain may be mediated by disturbances in the nitrergic system and increased
      lysosomal proteolysis.

PMID- 23010935
TI  - Chronic hyperammonemia, glutamatergic neurotransmission and neurological
      alterations.
AB  - This mini-review focus on our studies on alterations in glutamatergic
      neurotransmission and their role in neurological alterations in rat models of
      chronic hyperammonemia and hepatic encephalopathy (HE). Hyperammonemia impairs
      the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum, which is responsible
      for reduced learning ability. We studied the underlying mechanisms and designed
      treatments to restore the pathway and learning. This was achieved by treatment
      with: phosphodiesterase 5 inhibitors, cGMP, anti-inflammatories (ibuprofen), p38
      inhibitors or GABAA receptor antagonists (bicuculline). Hyperammonemia alters
      signal transduction associated to metabotropic glutamate receptors (mGluRs).
      Hypokinesia in hyperammonemia and HE is due to increased extracellular glutamate
      and mGluR1 activation in substantia nigra; blocking this receptor restores motor
      activity. The motor responses to mGluRs activation in nucleus accumbens (NAcc)
      are altered in hyperammonemia and HE, with reduced dopamine and increased
      glutamate release. This leads to activation of different neuronal circuits and
      enhanced motor responses. These studies show that altered responses to activation
      of NMDA receptors and mGluRs play essential roles in cognitive and motor
      alterations in hyperammonemia and HE and provide new treatments restoring
      cognitive and motor function.

PMID- 23010937
TI  - Plasma sex steroid hormonal profile and gonad histology during the annual
      reproductive cycle of river catfish Hemibagrus nemurus (Valenciennes, 1840) in
      captivity.
AB  - Plasma sex steroid hormonal profile and gonad histology were correlated to study
      the annual reproductive cycle of Hemibagrus nemurus. Hormones were measured by
      Enzyme Linked Immunosorbent Assay. Gonad tissues were observed by using light
      microscopy. The highest testosterone (T) value for male was observed in November
      and that of female was in October. 11-ketotestosterone (11-KT) and 17beta
      estradiol (E2) levels were highest in June and November, respectively. Hormonal
      profiles of T, 11-KT and E2 showed several peaks which indicated a non-seasonal
      pattern. There were significant differences (p < 0.05) in the monthly levels of
      T, 11-KT and E2. Gonadosomatic index of H. nemurus ranged from 1.14 +/- 0.02 % to
      7.06 +/- 1.40 %, and high gonadosomatic indices were recorded in May, August and
      November. Gonad histology revealed that spermatozoa were always present in the
      testes which implied continuous spermatogenesis and asynchronous ovarian
      development pattern was observed in the ovaries. The annual reproductive cycle of
      H. nemurus did not show a seasonal pattern and this indicate that H. nemurus is a
      non-seasonal breeder with several spawning cycles and can be referred to as
      indeterminate batch spawner. The major significances of this study are annual sex
      steroid hormonal profile and asynchronous ovarian development of H. nemurus. This
      information will contribute to our knowledge of reproductive biology of H.
      nemurus.

PMID- 23010936
TI  - Histopathological alterations in Senegal sole, Solea Senegalensis, from a
      polluted Huelva estuary (SW, Spain).
AB  - As a component of a large research project to evaluate the effects of
      contaminants on fish health in the field, histopathological studies have been
      conducted to help establish causal relationship between pollutants (heavy metals
      and aromatic polycyclic hydrocarbons--PAHs) and histopathological responses in
      Senegal sole, Solea senegalensis, from an estuary of SW Spain. Heavy metals (As,
      Zn, Cd, Pb, Cu and Fe) and 16 PAHs (proprietary USEPA) concentrations in water,
      sediment and tissues (liver and gills) and histopathological alterations in S.
      senegalensis from three sampling sites of Ria de Huelva estuary during 2004-2006
      years have been analysed. The histopathological studies revealed seasonal and
      spatial differences in the lesion grade of alterations observing the highest
      lesion grades in fish from Odiel River and autumn season. No significant
      differences were observed in the alterations prevalence between sampling sites,
      but significant differences were observed between seasons observing the highest
      prevalence in autumn season. However, calculated IPAT demonstrated a low-moderate
      impact of pollutants on health fish. Correlations between histopathological
      alterations and pollutants analysed were observed being heavy metals the group
      that presented a major number of correlations with alterations in several organs
      of S. senegalensis. In evaluating the general health of fish, the use of
      histopathological studies in recommended for making more reliable assessment of
      biochemical responses in fish exposed to a variety of environmental stressors.
      Statistical analysis using semiquantitative data on pathological lesions can help
      to establish correlation between cause (stressor) and effect (biomarker).

PMID- 23010938
TI  - A potential biomarker of androgen exposure in European bullhead (Cottus sp.)
      kidney.
AB  - The aim of this study was to identify a signal that could be used as an androgen
      exposure indicator in the European bullhead (Cottus sp.). For this purpose, the
      ultra-structure of the kidney was characterized to identify normal structure of
      this organ, and histological changes previously described in the kidney of
      breeding male bullheads were quantified using the kidney epithelium height (KEH)
      assay previously developed and validated for the stickleback. In the next step,
      the effect of trenbolone acetate (TbA), a model androgen, was assessed to
      identify potential androgenic regulation of bullhead kidney hypertrophy.
      Measurement of KEH performed on adult non-breeding male and female bullheads
      exposed for 14 and 21 days to 0, 1.26 and 6.50 MUg/L showed that kidney
      hypertrophy is induced in a dose-dependent manner, confirming the hypothesis that
      the European bullhead possesses a potential biomarker of androgen exposure.
      Combined with the wide distribution of the European bullhead in European
      countries and the potential of this fish species for environmental toxicology
      studies in field and laboratory conditions, the hypothesis of a potential
      biomarker of androgen exposure offers interesting perspectives for the use of the
      bullhead as a relevant sentinel fish species in monitoring studies. Inducibility
      was observed with high exposure concentrations of TbA. Further studies are needed
      to identify molecular signals that could be more sensitive than KEH.

PMID- 23010939
TI  - Effects of chemical and handling exposure on fatty acids, oxidative stress and
      morphological welfare indicators in gilt-head sea bream (Sparus aurata).
AB  - This work investigates the changes in the morphological traits, body composition,
      body fat and oxidative stress of Sparus aurata under two stress conditions: a low
      weekly exposure to the pesticide Diuron and chronic handling stress. The fish
      exposed to handling stress showed lower values in the morphological traits and
      perivisceral fat, whereas chemical stress induced a decrease in the percentage of
      muscle and carcase and an increase in the percentage of spleen and hepatosomatic
      index. The two stress situations produced changes in the FRAP (ferric reducing
      antioxidant power) levels in all organs studied with a particularly marked
      response for Diuron in the gill. No significant differences in the ROS (reactive
      oxygen species) level were found for the digestive tract or the gill. In muscle,
      only Diuron produced a significant increase in ROS, while in liver, both
      treatments increased the ROS levels. This supports the oxidative stress
      sensitivity to chemical stress and shows that also could be an appropriate
      indicator of handling stress. The morphological indexes and body components
      examined could be practical and easy welfare indicators. Nevertheless, further
      works must be needed to use under the production conditions in fish farms.

PMID- 23010940
TI  - Codon usage methods for horizontal gene transfer detection generate an abundance
      of false positive and false negative results.
AB  - Bacteria acquire new DNA in a process known as horizontal gene transfer (HGT). To
      investigate the evolutionary impact of this transfer of DNA, various methods have
      been developed to detect past HGT events. For example, codon usage-based methods
      detect the presence of transferred genes by identifying atypical patterns of
      codon usage. However, some inherited genes exhibit atypical codon usage and some
      transferred genes have codon usage patterns similar to those of the inherited
      genes. In this study, we used a comparative phylogenetic approach with
      Methylobacterium and Caulobacter species to demonstrate that even well-designed
      codon usage methods fail to detect many HGT events and generate a high rate of
      false positives (60-75 %) and false negatives (23-61 %). Therefore, we recommend
      caution when employing codon usage methods to identify transferred genes and
      suggest that the rapidly increasing availability of bacterial genome sequences
      makes the phylogenetic approach the method of choice.

PMID- 23010941
TI  - The impact of African Americans' beliefs about HIV medical care on treatment
      adherence: a systematic review and recommendations for interventions.
AB  - Disparities in access to and retention of regular HIV medical treatment persist
      among African Americans living with HIV. Many scholars believe that the mistrust
      of health care held by many African Americans stems from a legacy of abuse, from
      medical experimentation on slaves to the unethical practices with patients in the
      Tuskegee Syphilis study. We performed a systematic appraisal of the literature,
      using several key terms, in order to understand how attitudes about HIV-related
      health care influence African Americans' engagement in care. We examined peer
      reviewed studies published during the period January 2001 through May 2012. An
      initial search generated 326 studies. Sixteen descriptive studies met our
      inclusion criteria. Experiences of racism, conspiracy beliefs and the quality of
      provider relationships appeared to impact engagement. Providers should openly
      investigate personal beliefs that adversely affect their treatment decisions,
      listen to patient narratives, and share treatment decisions in order to create a
      transparent environment.

PMID- 23010943
TI  - Applause sign in Alzheimer's disease: relationships to cognitive profile and
      severity of illness.
AB  - The present study aims to investigate the potential clinical utility of applause
      sign in Alzheimer's disease (AD), exploring whether it is consequent to the
      severity of cognitive impairment or to specific neuropsychological profiles.
      According to the current debate, the role of apraxia is also investigated. A
      total of 105 patients with AD were enrolled and classified on the basis of the
      severity of the disease: 37 had mild AD, 38 moderate AD, and 30 severe AD. They
      were compared to 42 normal subjects. The applause sign was detected using the
      three clap test. All patients underwent a broad neuropsychological examination
      and 95 AD patients were tested for the presence of apraxia with a detailed praxis
      battery. Applause sign was present in all AD patient groups, which showed a
      significant difference with respect to normal controls, but not between each
      other. No significant difference was reported between apraxic and non-apraxic
      patients. Applause sign correlated with measures of frontal lobe dysfunction. No
      correlations were found between the applause sign and other cognitive functions
      examined.

PMID- 23010942
TI  - Interconnections in superior temporal cortex revealed by musicogenic seizure
      propagation.

PMID- 23010944
TI  - Angelo Mosso (1846-1910).

PMID- 23010945
TI  - Jorjani (1042-1137).

PMID- 23010946
TI  - Clifford Allbutt (1836-1925).

PMID- 23010947
TI  - TLR9 bone marrow chimeric mice define a role for cerebral TNF in neuroprotection
      induced by CpG preconditioning.
AB  - Systemic preconditioning with the TLR9 ligand CpG induces neuroprotection against
      brain ischemic injury through a tumor necrosis factor (TNF)-dependent mechanism.
      It is unclear how systemic administration of CpG engages the brain to induce the
      protective phenotype. To address this, we created TLR9-deficient reciprocal bone
      marrow chimeric mice lacking TLR9 on either hematopoietic cells or radiation
      resistant cells of nonhematopoietic origin. We report that wild-type mice
      reconstituted with TLR9-deficient hematopoietic cells failed to show
      neuroprotection after systemic CpG preconditioning. Further, while hematopoietic
      expression of TLR9 is required for CpG-induced neuroprotection it is not
      sufficient to restore protection to TLR9-deficient mice that are reconstituted
      with hematopoietic cells bearing TLR9. To determine whether the absence of
      protection was associated with TNF, we examined TNF levels in the systemic
      circulation and the brain. We found that although TNF is required for CpG
      preconditioning, systemic TNF levels did not correlate with the protective
      phenotype. However, induction of cerebral TNF mRNA required expression of TLR9 on
      both hematopoietic and nonhematopoietic cells and correlated with
      neuroprotection. In accordance with these results, we show the therapeutic
      potential of intranasal CpG preconditioning, which induces brain TNF mRNA and
      robust neuroprotection with no concomitant increase in systemic levels of TNF.

PMID- 23010948
TI  - Pilot results of in vivo brain glutathione measurements in stroke patients.
AB  - Measurement of glutathione concentration for the study of redox status in
      subjects with neurological disease has been limited to peripheral markers. We
      recruited 19 subjects with large strokes. Using magnetic resonance spectroscopy
      we measured brain glutathione concentration in the stroke region and in healthy
      tissue to calculate a glutathione-ratio. Elevated glutathione-ratio was observed
      in subacute (<72 hours) subjects without hemorrhagic transformation (mean=1.19,
      P=0.03, n=6). No trend was seen when all subjects were considered (n=19, 3 to 754
      hours, range=0.45 to 1.41). This technique can detect glutathione changes because
      of disease, and may be valuable in clinical trials of stroke and other
      neurological diseases.

PMID- 23010949
TI  - Statins and primary liver cancer: a meta-analysis of observational studies.
AB  - Statins are among the most commonly prescribed drugs used to manage dyslipidemia.
      Hepatocellular carcinoma is the third leading cause of cancer mortality and its
      rates have recently been increasing in central and northern Europe and USA. To
      quantify the association between statin use and risk for HCC, we performed a meta
      analysis of published studies. We conducted a MEDLINE search for observational
      studies reporting the association between exposure to statins and risk for
      incident liver cancer until March 2012. Fixed-effect and random-effect models
      were used to estimate summary relative risks (RR) and the corresponding 95%
      confidence intervals (CIs). Moreover, between-study heterogeneity and publication
      bias were assessed using adequate statistical tests. Five observational studies
      (two case-control and three cohort studies) based on 2574 cases of HCC were
      included. Statin treatment, compared with no treatment, was inversely related to
      HCC (summary RR=0.58; 95% CI 0.46-0.74). Between-study heterogeneity was
      significant (P<0.001) and numerically relevant (I=65%). When only longest statin
      use was considered, the RR was 0.66 (95% CI 0.55-0.80). Influence analysis on the
      overall estimate showed that heterogeneity was largely because of one study; when
      omitting it, the I dropped to 27% (P=0.240), whereas the summary RR was only
      marginally modified (RR=0.52; 95% CI 0.44-0.62). There was no evidence of
      publication bias. This meta-analysis suggests a favorable effect of statins on
      HCC, in the absence, however, of a duration-risk relationship.

PMID- 23010950
TI  - Lipoprotein(a) plasma levels and the risk of cancer: the PRIME study.
AB  - Although experimental studies have shown lipoprotein(a) antiangiogenic and
      antitumoral effects, the association of lipoprotein(a) levels with cancer in
      population studies remains elusive and poorly documented. The aim of this study
      was to analyse the relationship between lipoprotein(a) plasma levels and the
      incidence of cancer over 10 years of follow-up. Data from two French centres of
      the PRIME cohort were used, representing 5237 men aged 50-59 years and free from
      a history of cancer at baseline. Data on medical history, socioeconomic and
      lifestyle factors were obtained by questionnaire. Lipoprotein(a) plasma levels
      were analysed from fasting blood samples collected at baseline. The relationship
      between lipoprotein(a) levels and first incident cancer was studied using the
      multivariate Cox proportional hazards models for all-site and the main-site
      specific cancers, adjusted for various potential confounders including age,
      centre, smoking status and alcohol consumption. During follow-up, 456 new cancers
      were identified. No significant association was found between lipoprotein(a) and
      the all-site or main-site-specific cancers (hazard ratios for quartiles 2-4 vs.
      1, respectively: 1.24, 1.11, 1.29, P=0.23). However, a higher risk seemed to be
      observed for highest lipoprotein(a) levels in all sites, lung, colorectal or
      tobacco/alcohol-related cancers. For prostate cancer, the lowest risk was
      observed for the highest levels of lipoprotein(a) (P=0.12). In conclusion, no
      evident association was found between the lipoprotein(a) levels and the incidence
      of cancer. Nevertheless, a higher cancer risk seemed to be observed for the
      highest lipoprotein(a) levels. Further research focusing on the lipoprotein(a)
      qualitative structure, that is, apolipoprotein(a) polymorphism could help clarify
      this highly complex relation.

PMID- 23010951
TI  - Reaction on the acrylamide and cancer review by Lipworth and colleagues.

PMID- 23010952
TI  - A numerical study of microparticle acoustophoresis driven by acoustic radiation
      forces and streaming-induced drag forces.
AB  - We present a numerical study of the transient acoustophoretic motion of
      microparticles suspended in a liquid-filled microchannel and driven by the
      acoustic forces arising from an imposed standing ultrasound wave: the acoustic
      radiation force from the scattering of sound waves on the particles and the
      Stokes drag force from the induced acoustic streaming flow. These forces are
      calculated numerically in two steps. First, the thermoacoustic equations are
      solved to first order in the imposed ultrasound field taking into account the
      micrometer-thin but crucial thermoviscous boundary layer near the rigid walls.
      Second, the products of the resulting first-order fields are used as source terms
      in the time-averaged second-order equations, from which the net acoustic forces
      acting on the particles are determined. The resulting acoustophoretic particle
      velocities are quantified for experimentally relevant parameters using a
      numerical particle-tracking scheme. The model shows the transition in the
      acoustophoretic particle motion from being dominated by streaming-induced drag to
      being dominated by radiation forces as a function of particle size, channel
      geometry, and material properties.

PMID- 23010954
TI  - A fluorescent probe capable of detecting H2S at submicromolar concentrations in
      cells.
AB  - A new internal charge transfer (ICT) fluorescent probe for highly selective and
      sensitive monitoring of H(2)S has been developed. The design takes advantage of
      the facile reduction of non-fluorescent hydroxyamine naphthalimide by H(2)S to
      highly fluorescent amine naphthalimide. It has been demonstrated that the probe
      is able to detect H(2)S at submicromolar concentrations in cells.

PMID- 23010955
TI  - Local cooling reduces skin ischemia under surface pressure in rats: an assessment
      by wavelet analysis of laser Doppler blood flow oscillations.
AB  - The objectives of this study were to investigate the effects of local cooling on
      skin blood flow response to prolonged surface pressure and to identify associated
      physiological controls mediating these responses using the wavelet analysis of
      blood flow oscillations in rats. Twelve Sprague-Dawley rats were randomly
      assigned to three protocols, including pressure with local cooling (Deltat = -10 
      degrees C), pressure with local heating (Deltat = 10  degrees C) and pressure
      without temperature changes. Pressure of 700 mmHg was applied to the right
      trochanter area of rats for 3 h. Skin blood flow was measured using laser Doppler
      flowmetry. The 3 h loading period was divided into non-overlapping 30 min epochs
      for the analysis of the changes of skin blood flow oscillations using wavelet
      spectral analysis. The wavelet amplitudes and powers of three frequencies
      (metabolic, neurogenic and myogenic) of skin blood flow oscillations were
      calculated. The results showed that after an initial loading period of 30 min,
      skin blood flow continually decreased under the conditions of pressure with
      heating and of pressure without temperature changes, but maintained stable under
      the condition of pressure with cooling. Wavelet analysis revealed that stable
      skin blood flow under pressure with cooling was attributed to changes in the
      metabolic and myogenic frequencies. This study demonstrates that local cooling
      may be useful for reducing ischemia of weight-bearing soft tissues that prevents
      pressure ulcers.

PMID- 23010956
TI  - Er,Cr:YSGG laser influence on microleakage of class V composite resin
      restorations.
AB  - One of the most challenging issues following restoration is microleakage. The aim
      of this study was to investigate the effects of Er,Cr:YSGG laser with and without
      acid etching on microleakage of class V composite restorations. A total of 68
      human intact premolars were selected, disinfected, and randomly allocated to four
      experimental groups (n = 16) as well as positive and negative controls (n = 2
      each). Dimensionally, similar class V cavities were prepared on buccal surface of
      each tooth under the following conditions: group 1, bur cavity preparation and
      chemical etching (BE); group 2, bur cavity preparation and Er,Cr:YSGG laser
      conditioning (BLc); group 3, Er,Cr:YSGG laser cavity preparation and chemical
      etching (LE); and group 4, Er,Cr:YSGG laser cavity preparation and Er,Cr:YSGG
      laser conditioning (LLc). All samples were restored with composite. The teeth
      were sealed and immersed in 1 % methylene blue for 48 h before being sectioned.
      The microleakage evaluation was done under a stereomicroscope (*20). The leakage
      scores were recorded and Kruskal-Wallis and Mann-Whitney tests were used for
      statistical evaluations. The highest microleakage score was seen in gingival
      margins of group 4 (LLc) and the lowest in occlusal margins of group 3 (LE). The
      overall difference in leakage scores among the groups was statistically
      significant (p < 0.001) with gingival margins showing a significantly higher
      score than its occlusal counterparts (p < 0.001). It was noted that less
      microleakage could be achieved when cavities were prepared by laser compared to
      bur. In addition, less microleakage was seen in acid-etched cavities than laser
      conditioned counterparts. 

PMID- 23010957
TI  - How people construct their experience of living with secondary lymphoedema in the
      context of their everyday lives in Australia.
AB  - PURPOSE: The purpose of this work was to explore how men and women construct
      their experiences living with lymphoedema following treatment for any cancer in
      the context of everyday life. METHODS: The design and conduct of this qualitative
      study was guided by Charmaz' social constructivist grounded theory. To collect
      data, focus groups and telephone interviews were conducted. Audiotapes were
      transcribed verbatim and imported into NVivo8 to organize data and codes. Data
      were analyzed using key grounded theory principles of constant comparison, data
      saturation, and initial, focused, and theoretical coding. RESULTS: Participants
      were 3 men and 26 women who had developed upper- or lower-limb lymphoedema
      following cancer treatment. Three conceptual categories were developed during
      data analysis and were labeled "accidental journey," "altered normalcy," and "ebb
      and flow of control." "Altered normalcy" reflects the physical and psychosocial
      consequences of lymphoedema and its relationship to everyday life. "Accidental
      journey" explains the participants' experiences with the health care system,
      including the prevention, treatment, and management of their lymphoedema. "Ebb
      and flow of control" draws upon a range of individual and social elements that
      influenced the participants' perceived control over lymphoedema. These conceptual
      categories were interrelated and contributed to the core category of "sense of
      self," which describes their perceptions of their identity and roles.
      CONCLUSIONS: Results highlight the need for greater clinical and public awareness
      of lymphoedema as a chronic condition requiring prevention and treatment, and one
      that has far-reaching effects on physical and psychosocial well-being as well as
      overall quality of life.

PMID- 23010958
TI  - Symptom clusters and symptom interference of HCC patients undergoing TACE: a
      cross-sectional study in China.
AB  - OBJECTIVE: The aim of this study was to investigate the symptom and symptom
      clusters of patients with hepatocellular carcinoma (HCC) before and after
      transcatheter arterial chemoembolization (TACE), and to discuss the relationship
      between symptoms, symptom clusters, and symptom interference. MATERIALS AND
      METHODS: Patients with HCC who received TACE were asked to rate their symptoms
      using the M. D. Anderson Symptom Inventory and the symptom checklist particularly
      for HCC. To determine the interrelationships among symptoms and identify the
      symptom clusters, a principal component analysis with varimax rotation was
      carried out on the symptom items. Spearman correlation analysis was done to
      assess the relationship between symptom clusters and symptom interference.
      RESULTS: A total of 155 patients finished the whole procedure between November
      2010 and May 2011. Before TACE, the five most severe symptoms, ranked in order,
      were fatigue (3.40 +/- 2.26), distress (3.35 +/- 2.60), sadness (3.01 +/- 2.66),
      sleep disturbance (2.63 +/- 2.57), and lack of appetite (2.26 +/- 2.38). After
      TACE, fatigue (4.88 +/- 2.31) was the most serious symptom, followed by sleep
      disturbance (4.80 +/- 2.25), distress (4.59 +/- 2.32), sadness (4.45 +/- 2.16),
      lack of appetite (4.25 +/- 2.51). Two symptom clusters were found before TACE:
      psychological symptom cluster and sickness symptom cluster. Two new symptom
      clusters were found after TACE: upper gastrointestinal symptom cluster and liver
      function impairment symptom cluster, with the two original symptom clusters
      remained relatively stable. The highest symptom interference items pre- and post
      TACE were work and enjoyment of life, followed by mood. The symptoms of distress,
      sadness, fatigue, sleep disturbance, and lack of appetite were all significantly
      associated with the total interference (r = 0.443-0.615, p < 0.01 or p < 0.05).
      Symptom clusters were significantly correlated with the total symptom
      interference before and after TACE (r = 0.176-0.638, p < 0.01 or p < 0.05).
      CONCLUSION: Psychological symptom cluster and sickness symptom cluster are common
      for HCC patients before and after TACE. Liver function impairment and upper
      gastrointestinal symptom clusters are directly related to TACE treatment. Both
      the symptoms and symptom clusters have significant interference on the daily life
      of HCC patients undergoing TACE. However, more work is needed to further clarify
      the symptom clusters associated with TACE and to test the effectiveness of TACE
      in easing symptoms and improving quality of life of HCC patients.

PMID- 23010959
TI  - Continuous enteral administration can overcome the limited capacity to absorb
      glucose in rats with methotrexate-induced gastrointestinal mucositis.
AB  - BACKGROUND: Patients with chemotherapy-induced gastrointestinal mucositis often
      suffer from weight loss. It is not well known how to enterally feed mucositis
      patients, potentially experiencing malabsorption. Recently, we showed in a rat
      model of methotrexate (MTX)-induced mucositis that intestinal absorption of
      glucose in trace amounts is still intact. We now determined the quantitative
      capacity to absorb glucose in rats with mucositis, relative to controls. METHODS:
      We administered a physiologically relevant amount of [1-(13)C]glucose-enriched
      glucose (meal size) as a bolus by oral gavage (2 g/kg once) or continuously by
      intraduodenal infusion (+/-1.9 g/(kg.h) for 5 h) to rats with MTX-induced
      mucositis and controls. Blood [1-(13)C]glucose concentrations were determined
      during the experimental period. To calculate the quantitative absorptive
      capacity, Steele's one-compartment model, including simultaneous intravenous
      infusion of [6,6-(2)H(2)]glucose, was used. After the experiment, jejunal
      histology and plasma citrulline concentrations were assessed. RESULTS: MTX
      induced mucositis was confirmed by a reduction in villus length and plasma
      citrulline (both -57%, relative to controls, P < 0.01). When glucose was
      administered as a bolus, MTX-treated rats only absorbed 15% of administered
      glucose, compared with 85% in controls (medians, P < 0.01). Upon continuous
      intraduodenal glucose infusion, the median absorptive capacity for glucose in MTX
      treated rats did not differ from controls (80 versus 93% of administered glucose
      respectively, P = 0.06). However, glucose absorption differed substantially
      between individual MTX-treated rats (range, 21-95%), which correlated poorly with
      villus length (rho = 0.54, P = 0.030) and plasma citrulline (rho = 0.56, P =
      0.024). CONCLUSION: Continuous enteral administration can almost completely
      overcome the reduced absorptive capacity for glucose in rats with mucositis.

PMID- 23010960
TI  - Response to "A cross-sectional study of constipation and laxative use in advanced
      cancer patients: insights for revision of current practise".

PMID- 23010961
TI  - An evolution from 3D face-centered-cubic ZnSnO3 nanocubes to 2D orthorhombic
      ZnSnO3 nanosheets with excellent gas sensing performance.
AB  - We have successfully observed the development of three-dimensional (3D) face
      centered-cubic ZnSnO(3) into two-dimensional (2D) orthorhombic ZnSnO(3)
      nanosheets, which is the first observation of 2D ZnSnO(3) nanostructures to date.
      The synthesis from 3D to 2D nanostructures is realized by the dual-hydrolysis
      assisted liquid precipitation reaction and subsequent hydrothermal treatment. The
      time-dependent morphology indicates the transformation via a 'dissolution
      recrystallization' mechanism, accompanied by a 'further growth' process.
      Furthermore, the 2D ZnSnO(3) nanosheets consist of smaller sized nanoflakes. This
      further increases the special specific surface area and facilitates their
      application in gas sensing. The 2D ZnSnO(3) nanosheets exhibit excellent gas
      sensing properties, especially through their ultra-fast response and recovery.
      When exposed to ethanol and acetone, the response rate is as fast as 0.26 s and
      0.18 s, respectively, and the concentration limit can reach as low as 50 ppb of
      ethanol. All these results are much better than those reported so far. Our
      experimental results indicate an efficient approach to realize high-performance
      gas sensors.

PMID- 23010962
TI  - Weight in infancy and adult calcium absorption as determinants of bone mineral
      density in adult men: the Hertfordshire cohort study.
AB  - Adult bone mass is modified by early life environmental influences, but the
      mechanism of this association is uncertain. Data support an inverse relationship
      between intestinal calcium absorption (alphaCa) and birth weight in women.
      However, little is known regarding determinants in men. This study examines the
      association between weight in infancy and adult alphaCa in healthy men and
      whether this could be a mechanism by which the early life environment may
      influence bone mass. Men were recruited from the MRC Hertfordshire Cohort Study,
      for whom detailed early life records were available. Areal bone mineral density
      (aBMD) was measured using a Hologic QDR 4500 at the femoral neck (FN) and lumbar
      spine. We randomly selected 123 men stratified by birth weight and assessed
      alphaCa using the stable strontium absorption test. The mean age was 63.6 (SD
      2.5) years. alphaCa was not associated with birth weight or weight at 1 year. FN
      aBMD was associated with both weight at 1 year (r = 0.20, p = 0.03) and alphaCa
      (r = 0.20, p = 0.03). Both of these associations remained statistically
      significant in a mutually adjusted, multivariable model but would account for
      only ~4 % variance in BMD. We demonstrated a positive association between weight
      at 1 year and aBMD and between alphaCa and FN BMD, but no association was found
      between birth weight and alphaCa. This suggests that in men, although alphaCa is
      a contributing factor in FN bone density, it is not the main mechanism whereby
      the early environment modifies adult BMD.

PMID- 23010963
TI  - Stress-related gene expression changes in rainbow trout hepatocytes exposed to
      various municipal wastewater treatment influents and effluents.
AB  - The present study sought to examine the performance of six different wastewater
      treatment processes from 12 wastewater treatment plants using a toxicogenomic
      approach in rainbow trout hepatocytes. Freshly prepared rainbow trout hepatocytes
      were exposed to increasing concentrations of influent (untreated wastewaters) and
      effluent (C(18)) extracts for 48 h at 15  degrees C. A test battery of eight
      genes was selected to track changes in xenobiotic biotransformation,
      estrogenicity, heavy metal detoxification, and oxidative stress. The wastewaters
      were processed by six different treatment systems: facultative and aerated
      lagoons, activated sludge, biological aerated filter, biological nutrient
      removal, chemically assisted primary treated, and trickling filter/solids
      contact. Based on the chemical characteristics of the effluents, the treatment
      plants were generally effective in removing total suspended solids and chemical
      oxygen demand, but less so for ammonia and alkalinity. The 12 influents differed
      markedly with each other, which makes the comparison among treatment processes
      difficult. For the influents, both population size and flow rate influenced the
      increase in the following mRNA levels in exposed hepatocytes: metallothionein
      (MT), cytochrome P4503A4 (CYP3A4), and vitellogenin (VTG). Gene expression of
      glutathione S-transferase (GST) and the estrogen receptor (ER), were influenced
      only by population size in exposed cells to the influent extracts. The remaining
      genes-superoxide dismutase (SOD) and multidrug resistance transporter (MDR)-were
      not influenced by either population size or flow rate in exposed cells. It is
      noteworthy that the changes in MT, ER, and VTG in cells exposed to the effluents
      were significantly affected by the influents across the 12 cities examined.
      However, SOD, CYP1A1, CYP3A4, GST, and MDR gene expression were the least
      influenced by the incoming influents. The data also suggest that wastewater
      treatments involving biological or aeration processes had the best performance.
      We found that the effects of municipal effluents on gene expression depended on
      the population size, the initial properties of the incoming influent, and the
      wastewater treatment method applied. Considering that the long-term goals of
      wastewater treatment is to produce clean effluents for the aquatic biota and
      independent of the incoming influent, more research is needed in developing
      treatment processes to better protect aquatic life from anthropogenic
      contamination.

PMID- 23010965
TI  - Maturation (and deja vu) comes to the research in medical education program at
      age 51.

PMID- 23010964
TI  - Screening for potential effects of endocrine-disrupting chemicals in peri-urban
      creeks and rivers in Melbourne, Australia using mosquitofish and recombinant
      receptor-reporter gene assays.
AB  - Sexually mature male mosquitofish (Gambusia holbrooki) were collected from
      various sites around Melbourne in 2009 to evaluate the performance of gonopodial
      indices as a biomarker for endocrine disruption in Melbourne's waterways. The
      mosquitofish indices assessed were body length (BL), gonopodial length (GL)/BL
      ratio, ray 4:6 ratio and the absence or presence of hooks and serrae, and these
      varied between sites. The study was complemented by measurements of estrogenic,
      retinoid, thyroid and aryl hydrocarbon (AhR) receptor activities of the water.
      Male mosquitofish were 16.3-21.5 mm in length, and although there was a
      statistically significant positive relationship showing that bigger fish had
      longer gonopodia than small fish (r2 = 0.52, p < 0.001), there were few
      significant differences in GL/BL ratio of fish between sites. Measured estrogenic
      activity was mostly in the range 0.1-1.7 ng/L EEQ, with one site having much
      higher levels (~12 ng/L EEQ). Aryl hydrocarbon (AhR) receptor activity was
      observed in all water samples (7-180 ng/L betaNF EQ), although there was no
      consistent pattern in the level of AhR activity observed, i.e., 'clean' sites
      were as likely to return a high AhR activity response as urban or wastewater
      treatment plant (WWTP)-impacted sites. There was no correlation between
      measurements of receptor actvity and gonopodial length (GL):BL ratio and BL. We
      conclude that the mosquitofish gonopodia only fulfills part of the criteria for
      biomarker selection for screening. The mosquitofish indices assessed were cheap
      and easy-to-perform procedures; however, there is no baseline data from the
      selected sites to evaluate whether differences in the morpholical indices
      observed at a site were a result of natural selection in the population or due to
      estrogenic exposure.

PMID- 23010966
TI  - Additional perspectives on transforming science into medicine.

PMID- 23010967
TI  - Additional perspectives on transforming science into medicine.

PMID- 23010968
TI  - Additional perspectives on transforming science into medicine.

PMID- 23010972
TI  - Assessing the climate and culture around diversity and inclusion in academic
      medicine:  difficult but essential.

PMID- 23010973
TI  - Medical school logos:  how many snakes?

PMID- 23010974
TI  - Foreword:  a year of tradition, a year of change.

PMID- 23010975
TI  - Artist's statement: Champei's Petals.

PMID- 23010976
TI  - Medicine and the arts. Where the groceries went [excerpt]: by Raymond Carver.
      Commentary.

PMID- 23010978
TI  - 2012 Humanism in Medicine Essay Contest: Third Place: Fair trade chocolate.

PMID- 23010979
TI  - AM last page. Avoiding four visual-design pitfalls in survey development.

PMID- 23010980
TI  - What's in a name?

PMID- 23010981
TI  - The accuracy and reproducibility of SPECT target volumes and activities estimated
      using an iterative adaptive thresholding technique.
AB  - OBJECTIVE: Our aim was to design a practical and reproducible image segmentation
      method for calculations of total absorbed doses in organs and tumours for
      internally delivered radioisotopes. We have built upon our previously proposed
      use of two separate thresholds and employed an iterative technique for
      semiautomatic selection of background regions for segmenting an object of
      interest using thresholds that depend on the source-to-background ratio of
      activity concentrations. METHODS: The parameters of curves relating volume and
      activity thresholds to source-to-background ratio were established using phantoms
      with 20 different inserts. The accuracy of our technique was validated using a
      second phantom experiment, whereas the reproducibility of volume, activity and
      dose estimates of organs and tumours was investigated using 13 patient studies.
      The accuracy and reproducibility of segmentations achieved were assessed using
      images reconstructed with three different methods that ranged from a standard
      clinical reconstruction to an advanced quantitative reconstruction approach.
      RESULTS: In the validation phantom experiment, bottle volumes and activities
      measured using iterative adaptive thresholding agreed on average with the true
      values to within 4%, regardless of the reconstruction method used. In the patient
      studies, volumes and activities estimated from the single-photon emission
      computed tomography images reconstructed with clinical software agreed with the
      volumes and activities estimated using the advanced reconstruction approach to
      within 6%, whereas the corresponding doses agreed to within 4%. CONCLUSION: The
      proposed iterative adaptive thresholding technique can accurately determine
      object volume and activity, which allows standard clinical reconstructions to
      generate absorbed dose estimates that are similar to those values obtained using
      more advanced reconstruction methods.

PMID- 23010982
TI  - Design of an organic redox mediator and optimization of an organic counter
      electrode for efficient transparent bifacial dye-sensitized solar cells.
AB  - A new thiolate/disulfide mediator was designed and synthesized by employing DFT
      calculations as a guide. It possesses high transparency to visible light, a very
      attractive feature for bifacially active transparent DSCs that require a highly
      transparent counter electrode (CE). Compared to the reported and most promising
      thiolate/disulfide mediator T(-)/T(2), this new analogous mediator produced a
      major enhancement in open circuit potential (V(OC)) by about 40 mV and
      correspondingly a higher power conversion efficiency (eta) for DSCs. Furthermore,
      a highly uniform and transparent (transmittance > 91%) poly(3,4
      ethylenedioxythiophene) (PEDOT(BE)) CE was prepared and could efficiently
      catalyze the reduction of the disulfide. Based on the novel transparent redox
      couple and PEDOT(BE) CE, a new type of iodine-free and Pt-free transparent
      bifacial DSC was successfully fabricated. This new bifacial device could not only
      yield a promising front-illuminated eta of 6.07%, but also produce an attractive
      eta as high as 4.35% for rear-side irradiation, which exceeds the rear
      illuminated eta of 3.93% achieved for the same type of device, employing the dark
      colored I(-)/I(3)(-) electrolyte.

PMID- 23010983
TI  - Molecular cytogenetic characterization of the Amazon River dolphin Inia
      geoffrensis.
AB  - Classical and molecular cytogenetic (18S rDNA, telomeric sequence, and LINE-1
      retrotransposon probes) studies were carried out to contribute to an
      understanding of the organization of repeated DNA elements in the Amazon River
      dolphin (boto, Inia geoffrensis). Twenty-seven specimens were examined, each
      presenting 2n = 44 chromosomes, the karyotype formula 12m + 14sm + 6st + 10t +
      XX/XY, and fundamental number (FN) = 74. C-positive heterochromatin was observed
      in terminal and interstitial positions, with the occurrence of polymorphism.
      Interstitial telomeric sequences were not observed. The nucleolar organizer
      region (NOR) was located at a single site on a smallest autosomal pair. LINE-1
      was preferentially distributed in the euchromatin regions, with the greatest
      accumulation on the X chromosome. Although the karyotype structure in cetaceans
      is considered to be conserved, the boto karyotype demonstrated significant
      variations in its formula, heterochromatin distribution, and the location of the
      NOR compared to other cetacean species. These results contribute to knowledge of
      the chromosome organization in boto and to a better understanding of
      karyoevolution in cetaceans.

PMID- 23010984
TI  - Picomolar level profiling of the methylation status of the p53 tumor suppressor
      gene by a label-free electrochemical biosensor.
AB  - An efficient electrochemical approach is developed for ultrasensitive profiling
      of the methylation status of the p53 tumor suppressor gene based on a label-free
      biosensor in combination with bisulfite conversion.

PMID- 23010985
TI  - Regions, concepts and integrations.

PMID- 23010986
TI  - Energy restriction ameliorates metabolic syndrome-induced cavernous tissue
      structural modifications in aged rats.
AB  - High-fat (HF) diet regular intake along life highly contributes to vascular
      dysfunction and to an increment in prevalence of metabolic syndrome (MetS) and
      erectile dysfunction (ED), a surrogate symptom of occult vascular disease, in the
      elderly. However, little is known about the effects of energy restriction (ER)
      alone/or after an HF-feeding period. We show here that in male Sprague-Dawley
      rats, 16 months of HF-diet consumption led to an increase in body adiposity,
      blood pressure, lipidemia, C-reactive protein, and insulin resistance and to
      hypoadiponectinemia, conditions that cluster in MetS. In addition, this treatment
      strongly favored collagen deposition in cavernous tissue and myocardium.
      Conversely, for the same time period, the ingestion of 75 % of ad libitum energy
      intake by controls (ER) extensively counteracted these outcomes. The impact of 6
      month ER after 10-month HF period was also analyzed, and despite the decrease in
      body weight, adiposity, blood pressure, lipidemia, and C-reactive protein and
      improvement of insulin sensitivity, no differences were observed either in
      adiponectin blood levels or in retroperitoneal fat pad mass. Moreover, this
      treatment led to a reduction in cavernous tissue collagen deposition, but not in
      the myocardium, and evidenced differential mobilization of adipose tissue
      accretions. The data show the ability of HF diet to cause MetS and produce
      unwanted effects on myocardium and corpora vascular structure. They also indicate
      that these consequences are preventable upon ER diet starting early, but not
      later, in life.

PMID- 23010987
TI  - Facile formation of dendrimer-stabilized gold nanoparticles modified with
      diatrizoic acid for enhanced computed tomography imaging applications.
AB  - We report a facile approach to forming dendrimer-stabilized gold nanoparticles
      (Au DSNPs) through the use of amine-terminated fifth-generation poly(amidoamine)
      (PAMAM) dendrimers modified by diatrizoic acid (G5.NH(2)-DTA) as stabilizers for
      enhanced computed tomography (CT) imaging applications. In this study, by simply
      mixing G5.NH(2)-DTA dendrimers with gold salt in aqueous solution at room
      temperature, dendrimer-entrapped gold nanoparticles (Au DENPs) with a mean core
      size of 2.5 nm were able to be spontaneously formed. Followed by an acetylation
      reaction to neutralize the dendrimer remaining terminal amines, Au DSNPs with a
      mean size of 6 nm were formed. The formed DTA-containing [(Au(0))(50)-G5.NHAc
      DTA] DSNPs were characterized via different techniques. We show that the Au DSNPs
      are colloid stable in aqueous solution under different pH and temperature
      conditions. In vitro hemolytic assay, cytotoxicity assay, flow cytometry
      analysis, and cell morphology observation reveal that the formed Au DSNPs have
      good hemocompatibility and are non-cytotoxic at a concentration up to 3.0 MUM. X
      ray absorption coefficient measurements show that the DTA-containing Au DSNPs
      have enhanced attenuation intensity, much higher than that of [(Au(0))(50)
      G5.NHAc] DENPs without DTA or Omnipaque at the same molar concentration of the
      active element (Au or iodine). The formed DTA-containing Au DSNPs can be used for
      CT imaging of cancer cells in vitro as well as for blood pool CT imaging of mice
      in vivo with significantly improved signal enhancement. With the two radiodense
      elements of Au and iodine incorporated within one particle, the formed DTA
      containing Au DSNPs may be applicable for CT imaging of various biological
      systems with enhanced X-ray attenuation property and detection sensitivity.

PMID- 23010989
TI  - Management of acute atrial fibrillation in the emergency department: a systematic
      review of recent studies.
AB  - The aim of the study was to provide an overview on the current evidence on the
      method of cardioversion in patients presenting with recent-onset atrial
      fibrillation at the emergency department. ISI Web of Science and MEDLINE were
      explored for articles published between January 2000 and December 2011 in English
      or Spanish for the keywords 'acute', 'recent-onset' or 'paroxysmal' AND 'atrial
      fibrillation' AND 'treatment' AND 'emergency'. Original published articles were
      included if they enrolled patients with atrial fibrillation episodes of short
      duration (<48 h) and if they specifically addressed time to conversion, length of
      stay in the emergency department, safety, and/or relapses. Data extracted
      included the number of patients included, agent(s) studied, type and level of
      evidence of the article, rate of sinus rhythm conversion, time to conversion,
      discharge rate, length of stay, adverse events, embolic complications, and
      relapses. Fourteen papers were included in the review, eight of them prospective
      and randomized. Cardioversion in the emergency department had an overall high
      rate of conversion and few side-effects and/or embolic complications. Direct
      current cardioversion was the most effective therapeutic strategy in terms of
      sinus rhythm restoration, rate of discharge, length of stay, and safety. Class I
      drugs were also effective in a selected population. Amiodarone had a longer
      conversion time, with a similar rate of acute adverse events. Cardioversion in
      the emergency department is feasible and safe. Direct current cardioversion is
      the most effective therapeutic strategy.

PMID- 23010990
TI  - Numerical bifurcation analysis of the pattern formation in a cell based auxin
      transport model.
AB  - Transport models of growth hormones can be used to reproduce the hormone
      accumulations that occur in plant organs. Mostly, these accumulation patterns are
      calculated using time step methods, even though only the resulting steady state
      patterns of the model are of interest. We examine the steady state solutions of
      the hormone transport model of Smith et al. (Proc Natl Acad Sci USA 103(5):1301
      1306, 2006) for a one-dimensional row of plant cells. We search for the steady
      state solutions as a function of three of the model parameters by using numerical
      continuation methods and bifurcation analysis. These methods are more adequate
      for solving steady state problems than time step methods. We discuss a trivial
      solution where the concentrations of hormones are equal in all cells and examine
      its stability region. We identify two generic bifurcation scenarios through which
      the trivial solution loses its stability. The trivial solution becomes either a
      steady state pattern with regular spaced peaks or a pattern where the
      concentration is periodic in time. 

PMID- 23010991
TI  - Quiescence, excitability, and heterogeneity in ecological models.
AB  - Introducing quiescent phases into dynamical systems and ecological models tends
      to stabilize equilibria against the onset of oscillations and also to lower the
      amplitudes of existing periodic orbits. However, these effects occur when all
      interacting species go quiescent with the same rates and return to activity with
      the same rates. On the other hand, if the species differ with respect to these
      rates, then an equilibrium may even be destabilized. At least in the case of two
      interacting species this bifurcation phenomenon is closely related to the well
      known Turing instability. In particular, for two species it is true that an
      equilibrium can be destabilized by quiescent phases if and only if it is
      excitable in the Turing sense. These effects are thoroughly studied and exhibited
      at the example of classical ecological models and epidemic models. Similar
      effects occur in delay equations and reaction-diffusion equations. The effect of
      stabilization against oscillations by quiescent phases can be shown as a special
      realization of a general principle saying that spatial heterogeneity stabilizes.
      The results on local stability of stationary points can be extended to periodic
      orbits. In particular, a geometric argument on the flow along a periodic orbit
      explains why convex periodic orbits, as observed in numerical simulations, tend
      to shrink when quiescent phases are introduced.

PMID- 23010992
TI  - Multiscale time irreversibility of heart rate and blood pressure variability
      during orthostasis.
AB  - Time irreversibility is a characteristic feature of non-equilibrium, complex
      systems such as the cardiovascular control mediated by the autonomic nervous
      system (ANS). Time irreversibility analysis of heart rate variability (HRV) and
      blood pressure variability (BPV) represents a new approach to assess
      cardiovascular regulatory mechanisms. The aim of this paper was to assess the
      changes in HRV and BPV irreversibility during the active orthostatic test (a
      balance of ANS shifted towards sympathetic predominance) in 28 healthy young
      subjects. We used three different time irreversibility indices-Porta's, Guzik's
      and Ehler's indices (P%, G% and E, respectively) derived from data segments
      containing 1000 beat-to-beat intervals on four timescales. We observed an
      increase in the HRV and a decrease in the BPV irreversibility during standing
      compared to the supine position. The postural change in irreversibility was
      confirmed by surrogate data analysis. The differences were more evident in G% and
      E than P% and for higher scale factors. Statistical analysis showed a close
      relationship between G% and E. Contrary to this, the association between P% and
      G% and P% and E was not proven. We conclude that time irreversibility of beat-to
      beat HRV and BPV is significantly altered during orthostasis, implicating
      involvement of the autonomous nervous system in its generation.

PMID- 23010993
TI  - Fe3O4 nanoparticles: protein-mediated crystalline magnetic superstructures.
AB  - The synthesis of magnetic, monodisperse nanoparticles has attracted great
      interest in nanoelectronics and nanomedicine. Here we report the fabrication of
      pure magnetite nanoparticles, less than ten nanometers in size, using the cage
      shaped protein apoferritin (Fe(3)O(4)-ferritin). Crystallizable proteins were
      obtained through careful successive separation methods, including a magnetic
      chromatography that enabled the effective separation of proteins, including a
      Fe(3)O(4) nanoparticle (7.9 +/- 0.8 nm), from empty ones. Macroscopic protein
      crystals allowed the fabrication of three-dimensional arrays of Fe(3)O(4)
      nanoparticles with interparticle gaps controlled by dehydration, decreasing their
      magnetic susceptibilities and increasing their blocking temperatures through
      enhanced dipole-dipole interactions.

PMID- 23010994
TI  - Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without
      microsatellite instability.
AB  - BACKGROUND: The discovery of practical biomarkers is important to realize
      personalized medicine for patients with malignant neoplasias, including
      colorectal cancer (CRC). PURPOSE: The aim of this study was to determine reliable
      prognostic biomarkers by the analysis of patients with resectable colorectal
      liver metastases (CRLM). METHODS: Genomic DNA was obtained from the CRLM tissues
      of a cohort of 126 patients with CRLM with curative hepatic resection. The
      KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were
      successfully analyzed in 100 of the 126 CRLM tissues and these findings were
      examined in relation to the patients' clinical outcomes. RESULTS: The cohort of
      100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver
      metastasis. Overall survival and disease-free survival at 5 years were 57.4 and
      24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens
      showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM
      patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant
      (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the
      survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer
      prognoses compared with Wild-type patients. Furthermore, although the population
      with the BRAF mutation was small, this mutation had a significant negative impact
      on disease-free survival. CONCLUSIONS: In this study, all tumors in the cohort of
      CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would
      rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be
      poor prognostic factors in CRLM. Genetic information has an essential role as a
      prognostic marker and could contribute to the decisions on treatment strategy for
      CRLM.

PMID- 23010995
TI  - Characteristics of hepatic stem/progenitor cells in the fetal and adult liver.
AB  - BACKGROUND: The liver is an essential organ that maintains vital activity through
      its numerous important functions. It has a unique capability of fully
      regenerating after injury. Regulating a balance between self-renewal and
      differentiation of hepatic stem cells that are resources for functional mature
      liver cells is required for maintenance of tissue homeostasis. METHODS: This
      review describes the characteristics of hepatic stem/progenitor cells and the
      regulatory mechanism of their self-renewal and differentiation capacity. RESULTS:
      In liver organogenesis, undifferentiated hepatic stem/progenitor cells expand
      their pool by repeated self-renewal in the early stage of liver development and
      then differentiate into two different types of cell lineage, namely hepatocytes
      and cholangiocytes. Liver development is regulated by expression of stem cell
      transcription factors in a complex multistep process. Recent studies suggest that
      stem cells are maintained by integrative regulation of gene expression patterns
      related to self-renewal and differentiation by epigenetic mechanisms such as
      histone modification and DNA methylation. CONCLUSIONS: Analysis of the proper
      regulatory mechanism of hepatic stem/progenitor cells is important for
      regenerative medicine that utilizes hepatic stem cells and for preventing liver
      cancer through clarification of the carcinogenetic mechanism involved in stem
      cell system failure.

PMID- 23010996
TI  - Noise drives sharpening of gene expression boundaries in the zebrafish hindbrain.
AB  - Morphogens provide positional information for spatial patterns of gene expression
      during development. However, stochastic effects such as local fluctuations in
      morphogen concentration and noise in signal transduction make it difficult for
      cells to respond to their positions accurately enough to generate sharp
      boundaries between gene expression domains. During development of rhombomeres in
      the zebrafish hindbrain, the morphogen retinoic acid (RA) induces expression of
      hoxb1a in rhombomere 4 (r4) and krox20 in r3 and r5. Fluorescent in situ
      hybridization reveals rough edges around these gene expression domains, in which
      cells co-express hoxb1a and krox20 on either side of the boundary, and these
      sharpen within a few hours. Computational analysis of spatial stochastic models
      shows, surprisingly, that noise in hoxb1a/krox20 expression actually promotes
      sharpening of boundaries between adjacent segments. In particular, fluctuations
      in RA initially induce a rough boundary that requires noise in hoxb1a/krox20
      expression to sharpen. This finding suggests a novel noise attenuation mechanism
      that relies on intracellular noise to induce switching and coordinate cellular
      decisions during developmental patterning.

PMID- 23010997
TI  - A model of spatially restricted transcription in opposing gradients of activators
      and repressors.
AB  - Morphogens control patterns of transcription in development, often by
      establishing concentration gradients of a single transcriptional activator.
      However, many morphogens, including Hedgehog, create opposing activator and
      repressor gradients (OARGs). In contrast to single activator gradients, it is not
      well understood how OARGs control transcriptional patterns. We present a general
      thermodynamic model that explains how spatial patterns of gene expression are
      established within OARGs. The model predicts that differences in enhancer binding
      site affinities for morphogen-responsive transcription factors (TFs) produce
      discrete transcriptional boundaries, but only when either activators or
      repressors bind cooperatively. This model quantitatively predicts the boundaries
      of gene expression within OARGs. When trained on experimental data, our model
      accounts for the counterintuitive observation that increasing the affinity of
      binding sites in enhancers of Hedgehog target genes produces more restricted
      transcription within Hedgehog gradients in Drosophila. Because our model is
      general, it may explain the role of low-affinity binding sites in many contexts,
      including mammalian Hedgehog gradients.

PMID- 23010998
TI  - Novel biomarkers for pre-diabetes identified by metabolomics.
AB  - Type 2 diabetes (T2D) can be prevented in pre-diabetic individuals with impaired
      glucose tolerance (IGT). Here, we have used a metabolomics approach to identify
      candidate biomarkers of pre-diabetes. We quantified 140 metabolites for 4297
      fasting serum samples in the population-based Cooperative Health Research in the
      Region of Augsburg (KORA) cohort. Our study revealed significant metabolic
      variation in pre-diabetic individuals that are distinct from known diabetes risk
      indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin.
      We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2)
      and acetylcarnitine) that had significantly altered levels in IGT individuals as
      compared to those with normal glucose tolerance, with P-values ranging from
      2.4*10(-4) to 2.1*10(-13). Lower levels of glycine and LPC were found to be
      predictors not only for IGT but also for T2D, and were independently confirmed in
      the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam
      cohort. Using metabolite-protein network analysis, we identified seven T2D
      related genes that are associated with these three IGT-specific metabolites by
      multiple interactions with four enzymes. The expression levels of these enzymes
      correlate with changes in the metabolite concentrations linked to diabetes. Our
      results may help developing novel strategies to prevent T2D.

PMID- 23010999
TI  - Need-based activation of ammonium uptake in Escherichia coli.
AB  - The efficient sequestration of nutrients is vital for the growth and survival of
      microorganisms. Some nutrients, such as CO2 and NH3, are readily diffusible
      across the cell membrane. The large membrane permeability of these nutrients
      obviates the need of transporters when the ambient level is high. When the
      ambient level is low, however, maintaining a high intracellular nutrient level
      against passive back diffusion is both challenging and costly. Here, we study the
      delicate management of ammonium (NH4+/NH3) sequestration by E. coli cells using
      microfluidic chemostats. We find that as the ambient ammonium concentration is
      reduced, E. coli cells first maximize their ability to assimilate the gaseous NH3
      diffusing into the cytoplasm and then abruptly activate ammonium transport. The
      onset of transport varies under different growth conditions, but always occurring
      just as needed to maintain growth. Quantitative modeling of known interactions
      reveals an integral feedback mechanism by which this need-based uptake strategy
      is implemented. This novel strategy ensures that the expensive cost of upholding
      the internal ammonium concentration against back diffusion is kept at a minimum.

PMID- 23011000
TI  - Balancing risk in ophthalmic prescribing: assessing the safety of anti-VEGF
      therapies and the risks associated with unlicensed medicines.
AB  - Vascular endothelial growth factor (VEGF) inhibitor medications such as
      ranibizumab, pegaptanib and bevacizumab are in use for the treatment of
      neovascular age-related macular degeneration (AMD) and other retinal conditions,
      although only ranibizumab and pegaptanib are approved for these conditions. In
      contrast, bevacizumab was developed for the intravenous systemic treatment of
      colorectal cancer and is not formulated for intravitreal use, but is commonly
      used off-label in ophthalmology. European Union legislation permits the use of
      drugs outside the terms of their licence ('off-label') only under certain
      circumstances, such as during clinical trials, compassionate/named patient use in
      the absence of a licensed alternative, emergency scenarios (e.g., pandemics) or
      at the discretion of a treating physician. In such cases, patients should be
      fully informed regarding their treatment and any potential risks involved. Off
      label drug use can be an important tool to provide patients with treatment in
      cases of unmet medical need. However, the use of an unlicensed medicinal product,
      when a suitable licensed alternative is available, puts prescribing physicians at
      risk of liability if safety issues arise. Emerging clinical evidence suggests
      safety differences exist between ranibizumab and bevacizumab.

PMID- 23011001
TI  - Identification and evaluation of a thinning agent compatible with MegaCell DCS,
      an animal product-free corneal storage medium.
AB  - PURPOSE: MegaCell DCS, an animal product-free culture medium formulated for
      storing corneas, is superior to the traditionally used MEM (Eagle's) with Earles
      salts, Hepes, and supplemented with foetal calf serum (2 %), glutamine and an
      antibiotic cocktail (EB MEM). Because this medium does not prevent corneal
      swelling, and Dextran T500, which is traditionally used for reversing this
      process before transplant may have adverse effects on corneas, the purpose of the
      current investigation was to identify an alternative polymer that is compatible
      with MegaCell DCS. METHODS: Corneas maintained in MegaCell DCS or EB MEM were
      transferred to either EB MEM 5 % Dextran T500 or MegaCell DCS containing 5 %
      Dextran T500, 4 % polyethylene glycol (PEG) 10,000, PEG 35,000 (2 %, 3 %, 4 %) or
      Poloxamer 188 (4 %). Endothelial cell losses were determined and corneal
      hydration levels measured. Stromal cell cultures were generated and immunostained
      with anti alpha-SMA antibody. Janus Green was used to compare the viability of
      endothelial cells of corneas maintained in MegaCell DCS and EB MEM and
      respectively thinned with PEG 35,000 and Dextran T500. RESULTS: The rates of
      endothelial cell loss from corneas held in MegaCell DCS and thinned in MegaCell
      DCS containing 5 % Dextran T500, 4 % PEG 10,000 and 4 % Poloxamer 188 for 6 days
      were similar. When explants of these corneas were cultured myofibroblasts were
      generated. Although at concentrations of 4 % (w/v) both PEG 10,000 and Poloxamer
      188 caused excessive dehydration, the hydration levels of corneas held in
      MegaCell DCS containing 3 % PEG 35,000 were similar to those of corneas held in
      EB MEM 5 % Dextran T500. Endothelial cell losses after 6 days were negligible,
      explants of the corneas generated uniform fibroblastic stromal cell cultures and
      the extents of Janus Green staining were similar. Over 20 days the inclusion of 5
      % Dextran T500 in EB MEM but not 3 % PEG 35,000 in MegaCell DCS, increased the
      rate of endothelial cell loss. CONCLUSION: PEG 35,000 at a concentration of 3 %
      w/v does not induce endothelial cell loss and is compatible with MegaCell DCS for
      thinning corneas prior to transplantation.

PMID- 23011002
TI  - Effects of wearing yellow spectacles on visual skills, reading speed, and visual
      symptoms in children with reading difficulties.
AB  - BACKGROUND: Possible beneficial effects of yellow-tinted spectacle lenses on
      binocular vision, accommodation, oculomotor scanning, reading speed and visual
      symptoms were assessed in children with reading difficulties. METHODS: A
      longitudinal prospective study was performed in 82 non-dyslexic children with
      reading difficulties in grades 3-6 (aged 9-11 years) from 11 elementary schools
      in Madrid (Spain). The children were randomly assigned to two groups: a treatment
      (n = 46) and a without-treatment group (n = 36). Children in the treatment group
      wore yellow spectacle lenses with best correction if necessary over 3 months (in
      school and at home). The tests were first undertaken without the yellow filter.
      With best spectacle correction in each subject, measurements were made of:
      distance and near horizontal heterophoria, distance and near horizontal fusional
      vergence ranges, the accommodative convergence/accommodation (AC/A) ratio, near
      point of convergence (NPC), stereoacuity, negative relative accommodation (NRA)
      and positive relative accommodation (PRA), monocular accommodative amplitude
      (MAA), binocular accommodative facility (BAF), oculomotor scanning, and reading
      speed (words per minute). The Convergence Insufficiency Symptom Survey (CISS)
      questionnaire was completed by all children. After the 3-month period,
      measurements were repeated with the yellow lenses (treatment group) or without
      the yellow lenses (without-treatment group) but with refractive correction if
      needed. RESULTS: Over the 3 months, the two groups showed similar mean changes in
      the variables used to assess binocular vision, accommodation, oculomotor
      scanning, and reading speed. However, mean relative changes in convergence
      insufficiency symptoms differed significantly between the groups (p = 0.01).
      CONCLUSION: No effects of wearing yellow spectacles emerged on binocular vision,
      accommodation, oculomotor scanning, and reading speed in children with reading
      difficulties. The yellow filter had no effect even in children with low MAA and
      BAF. The reduction in visual symptoms observed in children with reading
      difficulties using the yellow filters was clinically insignificant.

PMID- 23011003
TI  - [Development of radiation oncology in Hungary. Their collaboration with
      developments in Germany as well as the importance of co-editorship of our jointly
      published journal Strahlentherapie und Onkologie].

PMID- 23011004
TI  - Controlling carrageenan structure using a novel formylglycine-dependent
      sulfatase, an endo-4S-iota-carrageenan sulfatase.
AB  - Carrageenans are sulfated polysaccharides that are found in the cell walls of red
      algae. These polysaccharides have gelling and texturizing properties that are
      widely appreciated in industrial applications. However, these functional
      properties depend strongly on the sulfation of the moieties of the carrabiose
      repetition unit. Here we aimed to monitor the sulfate composition of gelling
      carrageenan. To do so, we screened and purified from Pseudoalteromonas atlantica
      a 4S-iota carrageenan sulfatase that converts iota-carrabiose into alpha
      carrabiose units. The sequence of this protein matched the annotated Q15XH3
      (Uniprot databank) formylglycine-dependent sulfatase found in the P. atlantica
      genome. With pure enzyme, iota-carrageenan could be transformed into a hybrid
      iota-/alpha-carrageenan or pure alpha-carrageenan. Analysis of the distribution
      of the carrabiose moieties in hybrid carrageenan chain using enzymatic
      degradation with Alteromonas fortis iota-carrageenase, coupled with
      chromatography and NMR spectroscopy experiments, showed that the sulfatase has an
      endo mode of action. The endo-character and the specificity of the sulfatase made
      it possible to prepare hybrid kappa-/iota-/alpha-carrageenan and kappa-/alpha
      carrageenan starting from kappa-/iota-carrageenan.

PMID- 23011005
TI  - Gigabase-scale transcriptome analysis on four species of pearl oysters.
AB  - Pearl oysters have been found to secrete nacre and form pearls with good quality
      and significant commercial interest. However, the transcriptomic and genomic
      resources for pearl oysters are still limited. To improve this situation,
      transcriptome sequencing was conducted from four species of pearl oysters with
      Illumina HiSeqTM 2000. There were four gigabase-scale transcriptomes for four
      species of pearl oysters, ~26.3 million reads with ~2.37 gigabase base pairs
      (Gbp) in Pinctada fucata, ~26.5 million reads with ~2.39 Gbp in Pinctada
      margaritifera, ~27.0 million reads with ~2.43 Gbp in Pinctada maxima, and ~25.9
      million reads with ~2.33 Gbp in Pteria penguin, respectively. After sequence
      assembly and blastx alignment, the numbers of annotated unigenes >=200 bp were
      33,882 in P. fucata, 30,666 in P. margaritifera, 26,420 in P. maxima, and 29,928
      in P. penguin. Based on these annotated unigenes among four species of pearl
      oysters, CDSs were extracted and predicted and furthermore, analyses of GO and
      KEGG assignments were performed. In addition, 60 putative genes of growth factors
      and their receptors from four species of pearl oysters were predicted. This study
      established an excellent resource for gene discovery and expression in pearl
      oysters, but also offered a significant platform for functional genomics and
      comparative genomic studies for mollusks.

PMID- 23011007
TI  - Streptomyces bullii sp. nov., isolated from a hyper-arid Atacama Desert soil.
AB  - A Streptomyces strain isolated from a hyper-arid Atacama Desert soil was
      characterised using a polyphasic taxonomic approach. The strain, designated
      C2(T), had chemical and morphological properties typical of the genus
      Streptomyces. The isolate formed a branch in the Streptomyces 16S rRNA gene tree
      together with the type strain of Streptomyces chromofuscus and was also loosely
      related to Streptomyces fragilis NRRL 2424(T). DNA:DNA relatedness values between
      the isolate and its two phylogenetic neighbours showed that it formed a distinct
      genomic species. The strain was readily distinguished from these organisms using
      a combination of morphological and phenotypic data. Based on the genotypic and
      phenotypic results, isolate C2(T) represents a novel species in the genus
      Streptomyces, for which the name Streptomyces bullii sp. nov. is proposed. The
      type strain is C2(T) (=CGMCC 4.7019(T) = KACC 15426(T)).

PMID- 23011006
TI  - Two new anamorphic yeasts species, Cyberlindnera samutprakarnensis sp. nov. and
      Candida thasaenensis sp. nov., isolated from industrial wastes in Thailand.
AB  - Three yeast strains were isolated from industrial wastes in Thailand. Based on
      the phylogenetic sequence analysis of the D1/D2 region of the large subunit rRNA
      gene, the internal transcribed spacer (ITS1-5.8S rRNA gene-ITS2; ITS1-2) region,
      and their physiological characteristics, the three strains were found to
      represent two novel species of the ascomycetous anamorphic yeast. Strain JP52(T)
      represent a novel species which was named Cyberlindnera samutprakarnensis sp.
      nov. (type strain JP52(T); = BCC 46825(T) = JCM 17816(T) = CBS 12528(T), MycoBank
      no. MB800879), which was differentiated from the closely related species
      Cyberlindnera mengyuniae CBS 10845(T) by 2.9 % sequence divergence in the D1/D2
      region and 4.4 % sequence divergence in the ITS1-2. Strain JP59(T) and JP60 were
      identical in their D1/D2 and ITS1-2 regions, which were closely related to those
      of Scheffersomyces spartinae CBS 6059(T) by 0.9 and 1.0 % sequence divergence,
      respectively. In addition, supportive evidence of actin gene and translational
      elongation factor gene by sequence divergence of 6.5 % each confirmed their
      distinct status. Furthermore, JP59(T) and JP60 differentiated from the closely
      related species in some biochemical and physiological characteristics. These two
      strains were assigned as a single novel species which was named Candida
      thasaenensis sp. nov. (type JP59(T) = BCC 46828(T) = JCM 17817(T) = CBS 12529(T),
      MycoBank no. MB800880).

PMID- 23011008
TI  - Estimating changes of isotopic fractionation based on chemical kinetics and
      microbial dynamics during anaerobic methane oxidation: apparent zero- and first
      order kinetics at high and low initial methane concentrations.
AB  - Changes in natural isotopic composition may be used to reveal metabolic pathways
      of substrate transformation by microbial communities (Vavilin in Ecol Model
      240:84-92, 2012b). Anaerobic oxidation of methane (AOM) by sulfate has been
      described using a mathematical model based on chemical kinetics, microbial
      dynamics and equations for (13)C isotope accumulation in products as well as
      their redistribution between substrate and products. Experimental data for two
      batch cultures that originated from microbial mats covering methane seep chimneys
      in the Black Sea, previously obtained by Seifert et al. (Org Geochem 37:1411
      1419, 2006) and Holler et al. (Env Microbiol Reports 1(5):370-376, 2009), were
      used to model AOM. During long-time incubation, changes of isotope signatures in
      CH(4) showed that in the Seifert et al. batch tests (low methane concentration),
      in contrast to the Holler et al. batch tests (high methane concentration),
      methane production occurred along with methane oxidation. In accordance with the
      model, apparent zero and first-order kinetics of methane oxidation were valid for
      the Holler et al. and Seifert et al. batch tests, respectively. The observed
      change of [Formula: see text] was explained by microbial kinetics reflecting that
      the rate is lower for heavy substrate microbial utilization when compared to
      light substrate microbial utilization. The model showed that small amounts of
      methanogenesis will change the carbon isotopic composition of methane because
      biogenic methane has a distinct isotopic composition and due to the large
      difference between the maximum specific rates of methane oxidation and
      production. The estimated biomass doubling time of methane-oxidizers for high and
      low methane concentration was 408/126 days and 4640/1160 days, respectively,
      depending on the value of the half-saturation constant K ( S ) (5 and 20 mM).

PMID- 23011009
TI  - Comparative bacterial genomics: defining the minimal core genome.
AB  - A comparative genomics analysis revealed 702 genes present in the bacterial Gram
      negative core gene set (92 species analyzed) and 959 genes in the Gram-positive
      core gene set (93 species analyzed). Mycoplasma genitalium, which has the
      smallest known genome (517 genes) of a non-symbiont, was used in a three-way
      reciprocal analysis with the Gram-negative core genes and the Gram-positive core
      genes, and 151 common bacterial core genes were found. Of these 151 core genes,
      39 were putative genes encoding the 30S and 50S ribosomal subunits, whilst among
      recognized cell division genes, only one gene, the major ftsZ, was present. In
      addition, 86 reciprocal matches were identified between the 151 common bacterial
      genes and a previously determined 2,723 common eukaryotic core gene set. An
      analysis was also done to optimize the threshold bit score used to declare that
      genes were homologous, and a bit score cutoff of 40 was selected.

PMID- 23011010
TI  - Wangella harbinensis gen. nov., sp. nov., a new member of the family
      Micromonosporaceae.
AB  - A novel endophytic actinomycete, designated strain NEAU-J3(T), was isolated from
      soybean root (Glycine max (L.) Merr) and characterized using a polyphasic
      approach. Phylogenetic analysis based on 16S rRNA gene sequences suggested that
      strain NEAU-J3(T) fell within the family Micromonosporaceae. The strain was
      observed to form an extensively branched substrate mycelium, which carried non
      motile oval spores with a smooth surface. The cell walls of strain NEAU-J3(T)
      were determined to contain meso-diaminopimelic acid and galactose, ribose and
      glucose were detected as whole-cell sugars. The major menaquinones were
      determined to be MK-9(H(4)) and MK-9(H(6)). The phospholipids detected were
      phosphatidylcholine and phosphatidylethanolamine. The major cellular fatty acids
      were determined to be C(16:0), C(18:1) omega9c, C(18:0), C(17:0), C(17:1)
      omega7c, anteiso-C(17:0), C(16:1) omega7c and C(15:0). The DNA G + C content was
      62.5 mol%. On the basis of the morphological and chemotaxonomic characteristics,
      phylogenetic analysis and characteristic patterns of 16S rRNA gene signature
      nucleotides, strain NEAU-J3(T) is considered to represent a novel species of a
      new genus within the family Micromonosporaceae, for which the name Wangella
      harbinensis gen. nov., sp. nov. is proposed. The type strain of Wangella
      harbinensis is strain NEAU-J3(T) (=CGMCC 4.7039(T) = DSM 45747(T)).

PMID- 23011011
TI  - Evaluation of an interferon-gamma release assay in children with suspected
      tuberculosis in Papua New Guinea.
AB  - There are few data from tuberculosis (TB) endemic settings of the performance and
      outcome predictors of the QuantiFERON-TB Gold in Tube assay (QFT) in children
      with suspected TB. A prospective cross-sectional study was conducted in Papua New
      Guinea children with suspected TB evaluated at Port Moresby General Hospital
      (Port Moresby, Papua New Guinea). Two hundred sixteen children were enrolled
      including 106 probable TB, 87 possible TB and 23 without TB. Concordance between
      QFT and tuberculin skin test results was 86% (P < 0.001, kappa = 0.70). QFT was
      significantly more likely to be positive than tuberculin skin test, overall and
      within the probable or possible TB categories, with no difference in prevalence
      of positivity between these 2 categories. The role of QFT in supporting the
      clinical diagnosis of TB in endemic settings, where resources are limited,
      remains uncertain especially as cost and technical requirements remain
      considerable.

PMID- 23011012
TI  - Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine given to
      korean children receiving routine pediatric vaccines.
AB  - BACKGROUND: The immunogenicity and safety of 13-valent and 7-valent pneumococcal
      conjugate vaccines (PCV13 and PCV7) were compared when administered with routine
      vaccines in Korea. METHODS: Healthy infants (n = 180) were randomly assigned
      (1:1) to receive PCV13 or PCV7 at 2, 4, 6 (infant series) and 12 months (toddler
      dose). Immune responses 1 month after the infant series and toddler dose were
      measured by enzyme-linked immunosorbent assay and opsonophagocytic activity (OPA)
      assay. IgG antibody geometric mean concentrations and OPA functional antibody
      geometric mean titers were calculated. Safety was assessed. RESULTS: After the
      infant series, for the 7 common serotypes, proportions of responders with IgG
      concentrations >=0.35 ug/mL were comparable (>=97.6%) between groups; IgG
      geometric mean concentrations and OPA geometric mean titers were generally
      similar, but tended to be lower in the PCV13 group for some serotypes. For the 6
      serotypes unique to PCV13, IgG geometric mean concentrations and OPA geometric
      mean titers were notably higher in the PCV13 group. Importantly, although PCV7
      elicited IgG antibodies to PCV13 serotypes 5 and 19A, OPA responses were minimal,
      whereas serotype 6A elicited both IgG and OPA responses. These observations are
      consistent with at least some protection by PCV7 against 6A-mediated invasive
      pneumococcal disease, but no cross-protection for serotypes 5 and 19A. The
      toddler dose elicited higher IgG and OPA responses than postinfant series
      responses for most serotypes; however, for serotypes 3 and 14 only OPA responses
      were increased posttoddler dose. Vaccine safety profiles were similar.
      CONCLUSIONS: PCV13 is safe and immunogenic in Korean children. PCV13 should
      provide broader protection than PCV7.

PMID- 23011013
TI  - Group B Streptococcus and Escherichia coli infections in the intensive care
      nursery in the era of intrapartum antibiotic prophylaxis.
AB  - BACKGROUND: Group B Streptococcus (GBS) and Escherichia coli cause serious
      bacterial infections (SBIs) and are associated with morbidity and mortality in
      newborn infants. Intrapartum antibiotic prophylaxis reduces early-onset SBIs
      caused by GBS. The effect of intrapartum antibiotic prophylaxis on late-onset
      SBIs caused by these organisms is unknown. METHODS: We examined all blood, urine
      and cerebrospinal fluid culture results from infants admitted from 1997 to 2010
      to 322 neonatal intensive care units managed by the Pediatrix Medical Group. We
      identified infants with positive cultures for GBS or E. coli and compared the
      incidence of early- and late-onset SBI for each organism in the time period
      before (1997 to 2001) and after (2002 to 2010) universal intrapartum antibiotic
      prophylaxis recommendations. RESULTS: We identified 716,407 infants with
      cultures, 2520 (0.4%) with cultures positive for GBS and 2476 (0.3%) with
      cultures positive for E. coli. The incidence of GBS early-onset SBI decreased
      between 1997 to 2001 and 2002 to 2010 from 3.5 to 2.6 per 1000 admissions, and
      the incidence for E. coli early-onset SBI remained stable (1.4/1000 admissions in
      both time periods). Over the same time period, the incidence of GBS late-onset
      SBI increased from 0.8 to 1.1 per 1000 admissions, and incidence of E. coli late
      onset SBI increased from 2.2 to 2.5 per 1000 admissions. CONCLUSIONS: In our
      cohort, the incidence of GBS early-onset SBI decreased, whereas the incidence of
      late-onset SBI for E. coli and GBS increased.

PMID- 23011014
TI  - Statistical approaches to indirectly compare bioequivalence between generics: a
      comparison of methodologies employing artemether/lumefantrine 20/120 mg tablets
      as prequalified by WHO.
AB  - PURPOSE: The objective of this study was to compare different methods of adjusted
      indirect comparisons that can be used to investigate the relative bioavailability
      of different generic products. To achieve this goal, generic
      artemether/lumefantrine 20/120 mg tablets that have been prequalified by the
      World Health Organization (WHO) were selected as model products for study.
      METHODS: Data from three bioequivalence studies conducted independently that
      compared three generics with the same reference product were used to indirectly
      determine the relative bioavailability between the generics themselves. RESULTS:
      The different methods of indirect comparison examined in this study provide
      consistent results. Methods based on the assumption of a large sample size give
      slightly narrower 90 % confidence intervals. Therefore, the use of methods based
      on the t test is recommended. Given the precision of the area under the time
      concentration curve (AUC) data, it is possible to conclude that the extent of
      exposure of artemether and lumefantrine is bioequivalent between the different
      generics studied. However, given the precision of the drug peak concentration
      (C(max)) data, it is not possible to demonstrate equivalence within the
      conventional acceptance range for all comparisons; it is possible to conclude
      bioequivalence within the widened acceptance range 75-133 %. CONCLUSIONS: From a
      clinical viewpoint, not only are these prequalified generics bioequivalent and
      interchangeable with the reference product (Coartem, Novartis), but also the
      existing indirect evidence makes it possible to conclude that these WHO
      prequalified products are bioequivalent between themselves with respect to the
      AUC. The lack of the necessary precision to demonstrate bioequivalence between
      generics with respect to the C(max) within the conventional acceptance range does
      not preclude considering them as interchangeable, if necessary, since C(max) is
      considered to be of less clinical relevance for the relevant therapy.

PMID- 23011015
TI  - Drugs and Birth Defects: a knowledge database providing risk assessments based on
      national health registers.
AB  - PURPOSE: To present concept, methods and use of a knowledge database providing
      assessments of potential fetal risks for all drugs on the Swedish market.
      METHODS: Assessments of fetal risks are made primarily by analyzing prospective
      epidemiological data from the Swedish Medical Birth Register on drug intake in
      relation to birth outcome. This is complemented by evaluation of the scientific
      literature. Following standardized working procedures, a statement is compiled
      for each substance, which is also classified into one of three categories
      depending on the estimated risk level. The final documents include drug product
      names on the market, via linkage to a medicinal products register. The
      information is free and published on the website www.janusinfo.se . It can also
      be used as an integrated part of electronic health records. RESULTS: The database
      covers assessments of fetal risks for close to 1,250 medicinal drug substances on
      the Swedish market. Each year, 96,000 searches are made, which might be compared
      to the around 100,000 children born in Sweden yearly. Apart from the Swedish
      Physicians' Desk Reference (Fass), the database is the most commonly used
      resource among specialists within gynaecology and perinatal medicine for
      information on drugs during pregnancy. CONCLUSIONS: A non-commercial knowledge
      base with assessments of fetal risk of different drugs is valued by health care
      professionals and is used extensively in Sweden. Based on analyses of national
      health registers, the database provides unique information on teratogenic drug
      risks.

PMID- 23011016
TI  - Combretastatin A-4 derivatives: synthesis and evaluation of 2,4,5-triaryl-1H
      imidazoles as potential agents against H1299 (non-small cell lung cancer cell).
AB  - A number of 2,4,5-triaryl-1H-imidazole derivatives were synthesized and evaluated
      for their antiproliferative activities against the growth of five cell lines
      including three non-small cell lung cancers (H460, H1299, and A549), one breast
      cancer (MCF-7), and one normal diploid embryonic lung cell line (MRC-5).
      Preliminary results indicated that both 2-(5-bromofuran-2-yl)-4,5-bis{4-[3
      (dimethylamino) propoxy] phenyl}-1H-imidazole (10f) and 4,5-bis{4-[3
      (dimethylamino)propoxy]phenyl}-2-(5-nitrofuran-2-yl)-1H -imidazole (10g) were
      selectively active against the growth of H1229 with an IC(50) of less than 0.1
      MUM, thus were more active than topotecan (IC(50) > 10.0 MU M). However, both 10f
      and 10g exhibited only marginal cytotoxicity against H460, A549, MCF-7, and MRC-5
      requiring an IC (50) of at least 4.16 MUM. Our results also indicated that 10f
      induced H1299 cell cycle arrest at G0/G1 through the inactivation of p38 MAPK,
      JNK, ERK, as well as the expression of SIRT1 and survivin. These results
      suggested that 10f might have therapeutic potential against H1299 (non-small cell
      lung cancer cell).

PMID- 23011017
TI  - [Opening speech of the Congress President of the German Society for Pathology].

PMID- 23011018
TI  - [New S3 guidelines on exocrine pancreatic cancer].
AB  - In order to guarantee a unified application of the R classification, the S3
      guidelines were amended. With the introduction of the so-called CRM concept the
      special situation of ductal adenocarcinoma of the pancreas head can be taken into
      account. In contrast to the R classification, in the CRM concept lymph node
      metastases, lymph vessel and perineural sheath infiltration are taken into
      consideration. The distance of the tumor from the resection margins is
      particularly documented. Because of the prognostic significance of tumor-free
      lymph nodes, in future the lymph node ratio should be given. This is defined as
      the relationship of lymph node metastases to the total number of lymph nodes
      removed/examined.

PMID- 23011019
TI  - [Eosinophilic esophagitis. The gastroenterologist's perspective].
AB  - Eosinophilic esophagitis is characterized by symptoms of esophageal dysfunction
      and eosinophil-predominant esophageal inflammation. Eosinophilic inflammation in
      other parts of the gastrointestinal tract is absent and several differential
      diagnoses for esophageal eosinophilia have to be excluded before diagnosing
      eosinophilic esophagitis. Most patients are male and have concomitant atopic
      disorders. Therapeutic options are based on drugs, diet and dilation.

PMID- 23011020
TI  - [Update on Barrett esophagus and Barrett carcinoma].
AB  - The definition of Barrett esophagus is currently under discussion. It is now
      suggested that a distal esophagus coated with cylinder epithelium with cardia
      fundus mucosa should also be classified as Barrett esophagus because the risk of
      cancer is significantly increased even without histological evidence of
      intestinal metaplasia with goblet cells. The results of recent epidemiological
      investigations imply that the cancer risk of cylinder cell metaplasia and low
      grade intraepithelial neoplasia in Barrett esophagus has previously been
      overestimated. The histological detection of dysplasia still remains the best
      biomarker for estimation of the risk of cancer of Barrett esophagus. Exact
      determination of invasion depth in the mucosa, respective submucosa is now
      established as prognostic marker for overall survival in Patients with early
      carcinomas and this classification is useful for therapy decisions (endoscopic
      versus surgical removal). In advanced Barrett carcinoma following neoadjuvant
      therapy the lymph node status (ypN) is a better prognostic factor than the ypT
      category. In metastasized tumors therapies targeting HER2/new, EGFR or c-Met have
      been investigated explicitly in Barrett carcinoma only in phase I/II studies,
      whereby the predictive value of appropriate molecular pathology investigations is
      not yet reliably established.

PMID- 23011021
TI  - [New insights into the origin of pancreatic cancer. Role of atypical flat lesions
      in pancreatic carcinogenesis].
AB  - The identification and characterization of precursor lesions is fundamental to
      develop screening programs for early diagnosis and treatment, aiming at reducing
      cancer-related mortality. Pancreatic ductal adenocarcinoma (PDAC) is an
      aggressive disease that becomes clinical apparent only in advanced stages. In
      order to enable screening procedures for early detection of PDAC, an exact
      characterization of precursor lesions is of utmost importance. Pancreatic
      intraepithelial neoplasias (PanIN) are the most frequent and best characterized
      precursors of PDAC and are lesions with a ductal phenotype thus indicating a
      ductal cell origin of PDAC. However, evidence from genetically engineered mouse
      models suggests that tubular complexes (TC) originating through a process of
      acinar-ductal metaplasia (ADM) form atypical flat lesions (AFL) that may
      represent an alternative pathway of pancreatic carcinogenesis. Based on a
      thorough morphological and genetic analysis of murine TC, AFL and PanIN and their
      human counterparts, a new dual model of pancreatic carcinogenesis is proposed
      taking into account the role of AFL as possible new precursors of PDAC.

PMID- 23011022
TI  - [Application of digital pathology tools. An unusual case of non-Hodgkin
      lymphoma].
AB  - Currently, lymphoma diagnosis is based on a combination of morphology,
      immunophenotyping, and molecular testing. Using the example of an unusual case of
      malignant non-Hodgkin lymphoma, we show that improved visualization using digital
      pathology contributes to the convergence of these complementary diagnostic
      modalities. A 45-year-old woman presented with skin rash and cervical
      lymphadenopathy. Histological workup of an excised lymph node showed loss of
      normal architecture with diffuse infiltration and increased mitotic activity.
      Immunohistochemistry for CD3/CD5 showed atypical arrangement and infiltration of
      a T-cell population that dominated over regionally dense, MUM1-positive
      plasmacellular infiltrates. Expanded CD21/CD23-positive meshworks of follicular
      dendritic cells were present within and between regressed follicles and the T
      cell infiltrate; staining for CD56 and cyclin-D1 was negative. Quantification of
      Ki-67 staining within the T-, B- and plasmacellular compartments was achieved by
      digital image conversion, overlay and subsequent quantification algorithms that
      revealed proliferation within more than 60% of T-cells, over 50% of plasma cells
      and only 20% of B-cells. Clonality analysis by PCR revealed monoclonal
      rearrangement for both T-cell receptor gamma chains and immunoglobulin heavy
      chains. Taken together, we present an unusual combination of an
      angioimmunoblastic T-cell lymphoma (AITL) and simultaneous plasmacellular
      lymphoma. This report demonstrates how application of modern tools of digital
      pathology can visually integrate unusual morphological and molecular findings.

PMID- 23011023
TI  - [Eosinophilic esophagitis. Role of the pathologist in the diagnosis].
AB  - Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease
      with clinical symptoms and eosinophil-predominant inflammation. The diagnosis of
      EoE is therefore complex. It is not reflux or infectious or drug-induced.
      Histological cases with a high number of eosinophils are not a diagnostic
      problem. However, limits are of necessity in borderline cases. These must be
      based on the high power field (HPF) size and the percentage of squamous
      epithelium covering an HPF, which may greatly vary. Also, it must be considered
      that EoE is patchy in nature. In order to establish a reliable diagnosis a
      minimal number of biopsies is essential. Alongside the number of eosinophils
      further histological features associated with EoE, such as abcesses of
      eosinophils or basal layer enlargement, may be of diagnostic help in borderline
      cases.

PMID- 23011024
TI  - [Mechanisms of cell death. Novel insights and implications for tumor pathology].
AB  - During tumorigenesis cancer cells acquire certain features allowing for sustained
      growth and circumvention of programmed cell death. For decades cancer research
      has been focused on the molecular mechanisms of apoptosis and how to overcome
      apoptosis resistance in tumor cells. Meanwhile, novel types of programmed cell
      death have turned out to be important for both physiological and pathological
      processes. Recent findings imply that induction of alternative forms of
      programmed cell death, such as necroptosis, might be used as a therapeutic
      approach to overcome therapy resistance in cancer.

PMID- 23011026
TI  - [Report of the working group on molecular pathology. Minutes of the members
      meeting held as part of the 96th annual meeting of the DGP in Berlin].

PMID- 23011027
TI  - [Report of the meeting of the working group on hematopathology].

PMID- 23011028
TI  - [Report of the working group on cardiologic pathology and transplant].

PMID- 23011030
TI  - Type I IFN counteracts the induction of antigen-specific immune responses by
      lipid-based delivery of mRNA vaccines.
AB  - The use of DNA and viral vector-based vaccines for the induction of cellular
      immune responses is increasingly gaining interest. However, concerns have been
      raised regarding the safety of these immunization strategies. Due to the lack of
      their genome integration, mRNA-based vaccines have emerged as a promising
      alternative. In this study, we evaluated the potency of antigen-encoding mRNA
      complexed with the cationic lipid 1,2-dioleoyl-3trimethylammonium-propane/1,2
      dioleoyl-sn-glycero-3-phosphoethanolamine (DOTAP/DOPE ) as a novel vaccination
      approach. We demonstrate that subcutaneous immunization of mice with mRNA
      encoding the HIV-1 antigen Gag complexed with DOTAP/DOPE elicits antigen
      specific, functional T cell responses resulting in specific killing of Gag
      peptide-pulsed cells and the induction of humoral responses. In addition, we show
      that DOTAP/DOPE complexed antigen-encoding mRNA displays immune-activating
      properties characterized by secretion of type I interferon (IFN) and the
      recruitment of proinflammatory monocytes to the draining lymph nodes. Finally, we
      demonstrate that type I IFN inhibit the expression of DOTAP/DOPE complexed
      antigen-encoding mRNA and the subsequent induction of antigen-specific immune
      responses. These results are of high relevance as they will stimulate the design
      and development of improved mRNA-based vaccination approaches.

PMID- 23011031
TI  - Reducing mitochondrial ROS improves disease-related pathology in a mouse model of
      ataxia-telangiectasia.
AB  - The disease ataxia-telangiectasia (A-T) has no cure and few treatment options. It
      is caused by mutations in the ATM kinase, which functions in the DNA-damage
      response and redox sensing. In addition to severe cerebellar degeneration, A-T
      pathology includes cancer predisposition, sterility, immune system dysfunction,
      and bone marrow abnormalities. These latter phenotypes are recapitulated in the
      ATM null (ATM(-/-)) mouse model of the disease. Since oxidative stress and
      mitochondrial dysfunction are implicated in A-T, we determined whether reducing
      mitochondrial reactive oxygen species (ROS) via overexpression of catalase
      targeted to mitochondria (mCAT) alleviates A-T-related pathology in ATM(-/-)
      mice. We found that mCAT has many beneficial effects in this context, including
      reduced propensity to develop thymic lymphoma, improved bone marrow hematopoiesis
      and macrophage differentiation in vitro, and partial rescue of memory T-cell
      developmental defects. Our results suggest that positive effects observed on
      cancer development may be linked to mCAT reducing mitochondrial ROS, lactate
      production, and TORC1 signaling in transforming double-positive cells, whereas
      beneficial effects in memory T cells appear to be TORC1-independent. Altogether,
      this study provides proof-of-principle that reducing mitochondrial ROS production
      per se may be therapeutic for the disease, which may have advantages compared
      with more general antioxidant strategies.

PMID- 23011032
TI  - The efficacy versus toxicity profile of combination virotherapy and TLR
      immunotherapy highlights the danger of administering TLR agonists to oncolytic
      virus-treated mice.
AB  - Injection of oncolytic vesicular stomatitis virus (VSV) into established B16ova
      melanomas results in tumor regression, in large part by inducing innate immune
      reactivity against the viral infection, mediated by MyD88- and type III
      interferon (IFN)-, but not TLR-4-, signaling. We show here that intratumoral (IT)
      treatment with lipopolysaccharide (LPS), a TLR-4 agonist, significantly enhanced
      the local therapy induced by VSV by combining activation of different innate
      immune pathways. Therapy was further enhanced by co-recruiting a potent
      antitumor, adaptive T-cell response by using a VSV engineered to express the
      ovalbumin tumor-associated antigen ova, in combination with LPS. However, the
      combination of IT LPS with systemically delivered VSV resulted in rapid morbidity
      and mortality in the majority of mice. Decreasing the intravenous (IV) dose of
      VSV to levels at which toxicity was ameliorated did not enhance therapy compared
      with IT LPS alone. Toxicity of the systemic VSV + IT LPS regimen was associated
      with rapidly elevated levels of serum tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL)-6, which neither systemic VSV, nor IT LPS, alone induced. These
      data show that therapy associated with direct IT injections of oncolytic viruses
      can be significantly enhanced by combination with agonists of innate immune
      activation pathways, which are not themselves activated by the virus alone.
      Importantly, they also highlight possible, unforeseen dangers of combination
      therapies in which an immunotherapy, even delivered locally at the tumor site,
      may systemically sensitize the patient to a cytokine shock-like response
      triggered by IV delivery of oncolytic virus.

PMID- 23011033
TI  - Improved survival and reduced phenotypic severity following AAV9/MECP2 gene
      transfer to neonatal and juvenile male Mecp2 knockout mice.
AB  - Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function
      mutations in the methyl-CpG binding protein 2 (MECP2) gene. The demonstrated
      reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement
      is a potential therapeutic option in patients. We report improvements in survival
      and phenotypic severity in Mecp2-null male mice after neonatal intracranial
      delivery of a single-stranded (ss) AAV9/chicken beta-actin (CBA)-MECP2 vector.
      Median survival was 16.6 weeks for MECP2-treated versus 9.3 weeks for green
      fluorescent protein (GFP)-treated mice. ssAAV9/CBA-MECP2-treated mice also showed
      significant improvement in the phenotype severity score, in locomotor function,
      and in exploratory activity, as well as a normalization of neuronal nuclear
      volume in transduced cells. Wild-type (WT) mice receiving neonatal injections of
      the same ssAAV9/CBA-MECP2 vector did not show any significant deficits,
      suggesting a tolerance for modest MeCP2 overexpression. To test a MECP2 gene
      replacement approach in a manner more relevant for human translation, a self
      complementary (sc) adeno-associated virus (AAV) vector designed to drive MeCP2
      expression from a fragment of the Mecp2 promoter was injected intravenously (IV)
      into juvenile (4-5 weeks old) Mecp2-null mice. While the brain transduction
      efficiency in juvenile mice was low (~2-4% of neurons), modest improvements in
      survival were still observed. These results support the concept of MECP2 gene
      therapy for RTT.

PMID- 23011034
TI  - Effect of the polymorphisms of tumor necrosis factor-alpha gene on the
      susceptibility to primary biliary cirrhosis:  a meta-analysis.
AB  - BACKGROUND: Previous studies have shown the genetic association of tumor necrosis
      factor (TNF)-alpha polymorphisms and susceptibility to primary biliary cirrhosis
      (PBC), but the results of individual studies have remained contradictory.
      Therefore, a meta-analysis was carried out to evaluate comprehensively the
      association of TNF-alpha polymorphisms and susceptibility to PBC. METHODS: The
      relevant published articles were searched in PubMed, EMBASE, and Cochrane
      library. Data were extracted using standardized forms and odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated for each study. Pooled data were
      estimated by fixed-effects and random-effects models when appropriate. We
      analyzed the association between the 'A' allele at position -308(rs1800629) and 
      238(rs361525) and the risk of PBC. RESULTS: We examined eight publications,
      showing that all eight studies discussed the TNF-alpha -308(rs1800629)
      polymorphism; four studies were relevant with -238(rs361525). No significant
      associations were found between the 'A' allele frequency of rs1800629 and
      rs361525 and the risk of PBC in the overall population (OR=0.89, 95% CI 0.71
      1.11, P=0.91; OR=0.98, 95% CI 0.66-1.47, P=0.93) and in Whites (OR=0.94, 95% CI
      0.74-1.19, P=0.58; OR=1.01, 95% CI 0.64-1.59, P=0.97). Besides, it was also found
      that the genotype (AA+AG vs. GG, GG+AG vs. AA) was not linked to susceptibility
      to PBC. CONCLUSION: The meta-analysis indicated that none of these two
      polymorphisms (-308G/A and -238G/A) showed any significant association with the
      risk of PBC.

PMID- 23011035
TI  - An evaluation of patient attitudes to the gastroenterology outpatient experience.
AB  - OBJECTIVE: To determine patient attitudes in gastroenterology outpatient care,
      including the preferences and expectations associated with satisfaction, waiting
      times and quality in the consultation. METHODS: A service evaluation of patient
      care in outpatient gastroenterology clinics was carried out using a composite,
      dedicated self-completed questionnaire; this included demographics,
      preconsultation and postconsultation Likert scale attitudes to process,
      interactive and environmental factors and a 16-point ranking questionnaire of
      domains of the patient pathway considered important to obtaining satisfaction.
      RESULTS: Two hundred and twenty-seven patients agreed to participate. The factors
      considered most important to obtaining satisfaction related to the quality of the
      consultation, including 'seeing the doctor', 'having confidence in the treatment
      plan', 'clear and appropriately set explanations', 'being listened to',
      'opportunity to express important issues' and 'recognition of needs'. Low
      importance was attributed to process and environmental aspects including waiting
      times (appointment and waiting room), explanations for delays and the quietness
      and privacy of the consultation room, and involvement of the patient's next of
      kin. Patients reported dissatisfaction with long waiting times and short
      consultation times, but this did not appear to influence postconsultation
      satisfaction, the likelihood of reattendance or following the treatment plan.
      CONCLUSION: Patients consider that factors most important to a satisfactory
      experience in gastroenterology outpatient care relate specifically to the quality
      of their interaction with their healthcare professional in consultation. The
      roles of environmental and process issues are considered less important.

PMID- 23011036
TI  - Histologic evolution and long-term outcome of Wilson's disease:  results of a
      single-center experience.
AB  - BACKGROUND/AIMS: Wilson's disease (WD) is a rare inborn disease related to copper
      storage, leading to liver cirrhosis and neuropsychological deterioration. The aim
      of this study was to determine the clinical presentation and long-term outcome,
      and to examine the progression of hepatic histopathology in serial liver biopsies
      from WD patients. MATERIALS AND METHODS: We carried out a retrospective analysis
      of 60 patients with WD treated with zinc and/or penicillamine. Demographic,
      clinical, and laboratory data were gathered and 40 patients underwent an initial
      biopsy and at least one repeat biopsy. Patients were divided into two groups:
      progressors (patients who presented worsening of at least one unit of fibrosis)
      and nonprogressors (patients who presented stable or improved fibrosis scores).
      RESULTS: A total of 33/40 (83%) patients (nonprogressors) showed stable hepatic
      histology or improvement. Seven of 40 (17%) patients (progressors) showed
      worsening of fibrosis. There was no significant correlation between the
      histological findings and clinical parameters or initial presentation.
      CONCLUSION: In our study cohort, liver disease was stable or improving in most of
      the patients, and development of progressive hepatic symptoms while under
      treatment was a rare event. The development of new symptoms while under treatment
      or progression of pre-existing symptoms was more often recorded for neurological
      than for hepatic symptoms.

PMID- 23011037
TI  - Treatment with Peg-IFNalpha2a/ribavirin and low-dose NSAID for patients with
      chronic hepatitis C and rheumatoid syndrome.
AB  - OBJECTIVE: To examine the safety and efficiency of using Peg-IFNalpha2a/ribavirin
      and low-dose NSAID therapy in patients with rheumatoid syndrome (RS) and chronic
      hepatitis C (CHC). METHODS: A group of 10 patients (group 1) known to have RS and
      established CHC undergoing Peg-IFNalpha2a/ribavirin and low-dose NSAID therapy
      was compared with a control group of 10 patients (group 2) also with CHC and
      associated RS, with no antiviral treatment. Their charts were reviewed for
      serological and clinical signs of rheumatic disease evolution while undergoing
      this type of treatment. RESULTS: At the end of a follow-up period of 12 months,
      patients receiving low-dose NSAID and Peg-IFNalpha2a/ribavirin therapy showed a
      sustained virusological response and also decreased levels of inflammation
      serological markers, with an improvement in the clinical rheumatic symptoms. In
      contrast, patients in group 2 showed no significant clinical modification in
      their rheumatic status. CONCLUSION: Peg-IFNalpha2a/ribavirin and low-dose NSAID
      in patients with RS and CHC appear to be well tolerated and can be efficient for
      rheumatic manifestations. Further controlled studies are required to confirm the
      results.

PMID- 23011038
TI  - Role of hyaluronic acid, its degrading enzymes, degradation products, and
      ferritin in the assessment of fibrosis stage in Egyptian patients with chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: Liver biopsy is considered a gold standard for fibrosis staging,
      but it has a high risk of morbidity. Therefore, there is an interest in
      developing noninvasive markers for the prediction of liver fibrosis stages.
      METHODS: Hyaluronic acid, ferritin, N-acetyl-beta-D-glucosaminidase, beta
      glucuronidase, glucosamine, aspartate transaminase, and alanine transaminase were
      assayed in 210 individuals with chronic hepatitis C infection. Statistical
      analysis was carried out by logistic regression and receiver-operating
      characteristic curves. RESULTS: The best linear combination of only significant
      blood markers was used for the determination of the fibrosis discriminant score;
      score=[1.64 (numerical constant)-0.002*hyaluronic acid (pg/l)-2.68*beta
      glucuronidase (umol/ml/min)-0.026*glucosamine (ug/dl)-0.001*ferritin-0.033
      (ng/ml)*aspartate transaminase/alanine transaminase]. The selected fibrosis
      discriminant score function correctly classified 81% of patients with severe
      liver fibrosis at a discriminant cut-off score=0.55 (i.e. less than 0.55
      indicated mild liver fibrosis and greater than 0.55 indicated severe liver
      fibrosis), with a sensitivity of 100% and a specificity of 73%. CONCLUSION: A
      simple fibrosis index can be useful to select hepatitis C virus-infected patients
      with a very low risk of significant fibrosis in whom the protocol of liver
      biopsies may be avoided.

PMID- 23011039
TI  - Hepatitis C virus antibody positivity may not be associated with hepatitis C
      infection in patients with autoimmune gastritis.

PMID- 23011040
TI  - Serrated polyposis:  prospective study of first-degree relatives.
AB  - INTRODUCTION: Serrated polyposis (SP) is an infrequent colorectal cancer (CRC)
      predisposition syndrome. An unidentified genetic defect is believed to play a
      role in this condition. The risk of SP and/or CRC for first-degree relatives
      (FDRs) is not yet well known. The aim of our study was to determine the incidence
      of both SP and/or CRC by studying the FDRs of our index SP cases and to propose
      an appropriate interval for colonoscopy surveillance in this group. METHODS: From
      2005 to December 2011, we prospectively included all patients from our hospital
      who fulfilled the SP diagnostic criteria. We interviewed FDRs face to face and
      offered a colonoscopy to those who were 35 years old or older. The study was
      carried out with conventional and high-definition colonoscopes and
      chromoendoscopy with indigo carmine at the discretion of a single endoscopist.
      The samples were assessed by two pathologists. We reviewed the clinical data for
      CRC diagnosed previously in FDRs. RESULTS: From 2005, we collected all the new
      cases of SP and offered a colonoscopy to 95 FDRs of 34 pedigrees. We performed
      colonoscopies on 78 FDRs (82.1%). The incidence of SP in the FDRs was 32% (25
      patients). Seventy-six percent of patients were diagnosed with SP as they had any
      number of serrated polyps proximal to the sigmoid colon. Only one patient was
      diagnosed with CRC as a result of the screening colonoscopy. 44.1% of our index
      cases had an FDR with a diagnosis of CRC. CONCLUSION: Our series, which is the
      largest prospective cohort of FDRs published, reports an elevated incidence of SP
      in FDRs, thus supporting the need for screening colonoscopy in FDR and its
      inclusion in the guidelines.

PMID- 23011041
TI  - Reversal of sarcopenia predicts survival after a transjugular intrahepatic
      portosystemic stent.
AB  - BACKGROUND: Sarcopenia is the most frequent complication of cirrhosis. A
      transjugular intrahepatic portosystemic stent (TIPS) lowers portal pressure in
      cirrhosis and alters the body composition. Changes in the skeletal muscle area
      and adipose tissue volume were quantified by computed tomography (CT) before and
      after TIPS. MATERIALS AND METHODS: Fifty-seven consecutive cirrhotics who had a
      CT scan before and after TIPS were studied. Simultaneous age-matched, sex
      matched, Child's score-matched, and Model for End-Stage Liver Disease score
      matched cirrhotics (n=32) who did not undergo TIPS comprised the disease control
      and 57 healthy individuals who had undergone CT abdomen comprised the healthy
      control population. Muscle area and fat volume were obtained at the mid-L4
      vertebra level on the CT scans. RESULTS: Patients (mean age 55.5+/-8.1 years)
      were followed up for a mean of 13.5+/-11.9 months following TIPS. Total psoas and
      paraspinal muscle area increased significantly (P<0.0001) after TIPS (from 22.8+/
      0.9 to 25.1+/-0.9 cm and 54.5+/-1.3 to 57.9+/-1.5 cm, respectively). After TIPS,
      muscle area increased in 41 patients but remained unchanged or decreased in 16
      patients. Post-TIPS visceral fat volume decreased significantly (47.7+/-4.1 to
      40.5+/-3.4 cm; P<0.001). Failure to reverse sarcopenia after TIPS was accompanied
      by higher (P=0.007) mortality (43.5%) compared with patients in whom the total
      muscle area increased (9.8%). On multivariate analysis, predictors of reversal of
      sarcopenia after TIPS included male sex and lower pre-TIPS muscle area. Cirrhotic
      patients who did not undergo TIPS showed no change in the mean muscle area over
      13.1+/-1.3 months. CONCLUSION: TIPS reverses sarcopenia in cirrhotic patients.
      Failure to improve muscle area after TIPS was accompanied by a higher mortality.

PMID- 23011042
TI  - Crosslinked self-assemblies of lipoid acid-substituted low molecular weight (1800
      Da) polyethylenimine as reductive-sensitive non-viral gene vectors.
AB  - In this study, amphiphilic polyethylenimine-graft-thioctic acid (PEI-TA) and
      polyethylenimine-graft-lauric acid (PEI-LA) were synthesized. Both PEI-TA and PEI
      LA could self-assemble into micelles. Due to the existence of disulfide-linked
      rings at the end of hydrophobic moieties, PEI-TA could form stable micelles with
      disulfide crosslinked cores (PEI-TA-SS). In comparison with the PEI-LA micelle,
      PEI-TA-SS possessed higher DNA binding ability according to the gel retardation
      assay and heparin replacement assay. In vitro transfection experiments indicated
      that PEI-TA-SS showed comparably high transfection efficiency as compared to 25
      kDa PEI. More interestingly, the luciferase expression of PEI-TA-SS was superior
      to that of PEI-LA at low N/P ratio, which might be ascribed to the stronger
      binding capacity of PEI-TA-SS facilitating the entering of PEI-TA-SS/pDNA
      complexes into cells.

PMID- 23011043
TI  - [EzPAP(r) therapy of postoperative hypoxemia in the recovery room : experiences
      with the new compact system of end-expiratory positive airway pressure].
AB  - BACKGROUND: Postoperative hypoxemia is a common complication in the anesthesia
      recovery room (ARR), which is predominantly based on the development of
      atelectasis, excessive intraoperative fluid shift and insufficient ventilation.
      The goal of this prospective observational study was to compare the effect of
      standard oxygen administration via a face mask with oxygen administration using
      the EzPAP(r) system, a device which additionally provides a positive end
      expiratory pressure (PEEP). METHODS: This study included 210 patients with
      postoperative hypoxemia (S(p)O(2) < 93%) subdivided into the control group (105
      patients) and the EzPAP group (105 patients). Postoperative residual paralysis
      was excluded using relaxometry and a train of four (TOF) ratio of 0.9 was assumed
      to ensure sufficient recovery of respiratory function from neuromuscular
      blockade. Patients who received a reversal of neuromuscular blockade were
      excluded. In cases of hypoxemia (S(p)O(2) < 93%) control patients were treated
      with oxygen (6 l/min) using a face mask, whereas the EzPAP group received oxygen
      using the EzPAP(r) system. In order to adjust the PEEP in the EzPAP group, the
      O(2) flow was verified and measured by a manometer. After 1 h of oxygen therapy,
      the oxygen supply was stopped. In cases of reoccurring hypoxemia (S(p)O(2) < 93%,
      persistence > 5 min), the oxygen therapy was restarted in both groups via a
      facemask. Both groups were compared using repeat measurement analysis of variance
      (ANOVA), the unpaired t-test, the Mann-Whitney U-test, Fisher's exact test and
      the chi(2)-test. The correlation of O(2) flow and PEEP was evaluated by
      regression analysis and p < 0.05 was considered to be statistically significant.
      Apart from this a subgroup analysis was performed depending on body-mass index
      (BMI), American Society of Anesthesiologists (ASA) classification, intraoperative
      airway management, the use of neuromuscular blocking agents and co-existing
      disorders, e.g. chronic obstructive lung disease (COLD), obesity and chronic
      heart failure. RESULTS: All patients were equally distributed between both groups
      with respect to demographic data, ASA classification, BMI, co-existing disorders
      and surgical procedures. The S(p)O(2) values did not differ between the EzPAP
      patients and the control group, except for 0.5 min after initiation of oxygen
      therapy: EzPAP group 96 +/- 3.7% (mean +/- standard deviation) versus the control
      group 93.8 +/- 4.4% (p < 0.001). However, restarting oxygen therapy was less
      common in the EzPAP group (EzPAP group 25 versus control group 41, p = 0.03), as
      well as the occurrence of postoperative complications (EzPAP group 13 versus
      control group 25, p = 0.02), e.g. nosocomial pneumonia (0 versus 4) and wound
      infections (2 versus 3). Furthermore, patients with obesity and pulmonary
      disorders, such as COLD had a benefit from oxygen administration using the EzPAP
      device and showed higher postoperative than preoperative S(p)O(2) values. In
      contrast, the subgroup analysis of patients with heart failure did not reveal any
      differences between both groups and both groups did not differ in terms of time
      spent in the recovery room (EzPAP group 113 min versus control group 174.8 min, p
      = 0.2). CONCLUSIONS: In this observational study oxygen supply using the EzPAP(r)
      system appeared to be at least equally as effective in the therapy of
      postoperative hypoxemia compared to standard oxygen supply using a face mask. In
      patients with a high risk of postoperative hypoxemia, such as patients with
      obesity and/or pulmonary disorders, oxygen administration using the EzPAP(r)
      system possibly improves pulmonary oxygenation more effectively and is longer
      lasting compared to standard oxygen supply via a face mask. Hence, the EzPAP(r)
      system represents a well-tolerated, effective, cost-effective and easily operated
      tool to improve postoperative oxygenation. In order to investigate the
      possibilities of this promising tool more intensively, randomized clinical trials
      are warranted.

PMID- 23011044
TI  - [Do residents and nurses communicate safety relevant concerns? : simulation study
      on the influence of the authority gradient].
AB  - BACKGROUND: Due to the negative impact on decision-making too steep authority
      gradients in teams represent a risk factor for patient safety. As residents and
      nursing staff may fear sanctions they may be reluctant to forward critical
      information to or challenge planned actions of attending physicians. In the
      setting of a simulation course it was investigated whether and to what extent
      team members would challenge decisions of familiar attending physicians. In each
      case where participants did not voice an opinion the underlying motives for the
      behavior were investigated. METHODS: A total of 59 physicians and 18 nursing
      staff participated in the scenario. During a rapid sequence induction they were
      confronted with 7 critical situations created by the attending physician who had
      been instructed by the simulation team. Recommendations of the German Society of
      Anaesthesiology were ignored as well as clinical standard operating procedures
      (SOPs) and two potentially fatal drug administrations were ordered. An attempt
      was made to determine whether team members were aware of the safety threat at all
      and if so how they would solve the resulting conflicts. The level of verbal
      challenge was scored. During debriefing participants were asked to verbalize the
      motives which they thought might account for their silence or level of challenge.
      RESULTS: In situations where non-verbal conflict resolution was possible 65% of
      the participants pursued that strategy whereas 35% voiced an opinion. Situations
      necessitating verbal intervention were identified in 66% but 72% of the
      participants chose to remain silent. Team members decided to challenge the
      attending physician in only 28% of the situations. In 35% their statement was
      oblique, in 25% the problem was addressed but not further pursued and only in 40%
      did participants show crisp advocacy and assertiveness and initiated discussion.
      Asked why they had refrained from challenging the attending physician 37% had no
      answer, in 35% of situations participants observed a discrepancy between their
      own knowledge and the intended course of action yet they decided not to address
      the problem, 12% explained their behavior with the perceived authority of the
      attending physician and 8% stated that in their opinion attending physicians
      violated SOPs on a daily basis. None of the participants had the feeling that the
      simulation setting had provoked a response different to what they might have done
      in everyday life. CONCLUSIONS: The authority gradient can have a major negative
      impact on perioperative patient care. Residents and nursing staff are seldom able
      to challenge the attending physicians when patient safety is at risk. However,
      even attending physicians who normally accept feedback and criticism from team
      members can fail to receive support.

PMID- 23011045
TI  - [Near-infrared spectroscopy in sepsis therapy : predictor of a low central venous
      oxygen saturation].
AB  - BACKGROUND: Early goal-directed hemodynamic optimization has become a cornerstone
      of sepsis therapy. One major defined goal is to achieve adequate central venous
      oxygen saturation (SO(2)). This study aimed to investigate the correlation
      between central venous SO(2) and frontal cerebral near-infrared spectroscopy
      (NIRS) measurement in patients with severe sepsis and septic shock. The NIRS
      method provides non-invasive measurement of regional oxygen saturation (rSO(2))
      in tissues approximately 2 cm below the optical NIRS sensors which depends on
      arterial, capillary and venous blood. Thus this system gives site-specific real
      time data about the balance of oxygen supply and demand. METHODS: This was a
      secondary analysis from a prospective study of surgical intensive care (ICU)
      patients in the early phase of severe sepsis or septic shock. Bilateral cerebral
      rSO(2), central venous SO(2), arterial oxygen saturation (S(a)O(2)) and other
      surrogate parameters of oxygen supply, such as hemoglobin, partial pressure of
      oxygen and oxygen content in arterial blood were recorded. RESULTS: A total of 16
      ICU patients (4 women, median age 65.5 years) were included in the study. As
      sepsis focus an intra-abdominal infection was detected in 62.5 % of patients,
      severe pneumonia was determined in 31.3 % and skin and soft tissue infections
      were recognized in 12.5 %. At study inclusion 50 % of patients had septic shock,
      the median sequential organ failure assessment (SOFA) score was 10.2
      (interquartile range 5.25-8.75) and the median acute physiology and chronic
      health evaluation II (APACHE II) score was 26 (range 23.25-29.75). Mortality at
      day 28 was 37.5 %. Minimum rSO(2) (median 58) and right-sided rSO(2) (median 58)
      values showed a significant correlation in the analysis of receiver operating
      characteristics (area under the curve 0.844, p= 0.045). A central venous SO(2)<
      70 % was indicated by rSO(2)< 56.5 with sensitivity and specificity of 75 % and
      100 %, respectively. CONCLUSIONS: Cerebral NIRS could provide a fast and easily
      available side effect-free monitoring that could be used in addition to
      established procedures for goal-directed treatment in the early phase of sepsis.
      Further studies should be made in a larger population to verify the correlation
      found and to investigate the impact of NIRS-directed resuscitation treatment in
      early sepsis.

PMID- 23011046
TI  - Introduction: experimenting with animals in the early modern era.
AB  - The aim of this special issue is to address issues surrounding the use of live
      animals in experimental procedures in the pre-modern era, with a special emphasis
      on the technical, anatomical, and philosophical sides. Such use raises
      philosophical, scientific, and ethical questions about the nature of life, the
      reliability of the knowledge acquired, and animal suffering.

PMID- 23011047
TI  - Adolf naef (1883-1949): on foundational concepts and principles of systematic
      morphology.
AB  - During the early twentieth century, the Swiss Zoologist Adolf Naef (1883-1949)
      established himself as a leader in German comparative anatomy and higher level
      systematics. He is generally labeled an 'idealistic morphologist', although he
      himself called his research program 'systematic morphology'. The idealistic
      morphology that flourished in German biology during the first half of the
      twentieth century was a rather heterogeneous movement, within which Adolf Naef
      worked out a special theoretical system of his own. Following a biographical
      sketch, we present an English translation of a previously unpublished typescript
      from Naef's estate, which Naef intended as the introduction to a textbook on
      Comparative Anatomy for which he was unable to find a publisher before his sudden
      death in 1949. The typescript contains Naef's mature thoughts with unprecedented
      conciseness, focus, and clarity. The density of Naef's text warrants a historical
      and contextual explication of its content. 

PMID- 23011048
TI  - Detection of mercury ions based on mercury-induced switching of enzyme-like
      activity of platinum/gold nanoparticles.
AB  - In this study, bimetallic platinum/gold nanoparticles (Pt/Au NPs) were found to
      exhibit peroxidase-like activity, and the deposition of mercury was found to
      switch the enzymatic activity to a catalase-like activity. Based on this
      phenomenon, we developed a new method for detecting mercury ions through their
      deposition on bimetallic Pt/Au NPs to switch the catalytic activity of Pt/Au NPs.
      Pt/Au NPs could be easily prepared through reduction of Au(3+) and Pt(4+) by
      sodium citrate in a one-pot synthesis. The peroxidase catalytic activity of the
      Pt/Au NPs was controlled by varying the ratios of Pt to Au. The Pt(0.1)/Au NPs
      (prepared with a [Au(3+)]/[Pt(4+)] molar ratio of 9.0/1.0) showed excellent
      oxidation catalysis for H(2)O(2)-mediated oxidation of Amplex(r) Red (AR) to
      resorufin. The oxidized product of AR, resorufin, fluoresces more strongly
      (excitation/emission wavelength maxima ca. 570/585 nm) than AR alone. The
      peroxidase catalytic activity of Pt(0.1)/Au NPs was switched to catalase-like
      activity in the presence of mercury ions in a 5.0 mM
      tris(hydroxymethyl)aminomethane (Tris)-borate solution (pH 7.0) through the
      deposition of Hg on the particle surfaces owing to the strong Hg-Au metallic
      bond. The catalytic activity of Hg-Pt(0.1)/Au NPs is superior (by at least 5
      fold) to that of natural catalase (from bovine liver). Under optimal solution
      conditions [5.0 mM Tris-borate (pH 7.0), H(2)O(2) (50 mM), and AR (10 MUM)] and
      in the presence of the masking agents polyacrylic acid and tellurium nanowires,
      the Pt(0.1)/Au NPs allowed the selective detection of inorganic mercury (Hg(2+))
      and methylmercury ions (MeHg(+)) at concentrations as low as several nanomolar.
      This simple, fast, and cost-effective system enabled selective determination of
      the spiked concentrations of Hg(2+) and MeHg(+) in tap, pond, and stream waters.

PMID- 23011049
TI  - Musculoskeletal: what's different in children? Steps in hole: pain in the
      forefoot.

PMID- 23011050
TI  - CT of the skin and subcutaneous tissues.
AB  - A broad spectrum of skin and subcutaneous (SQ) findings may be discovered in the
      emergency setting on CT examinations. There are some findings that are directly
      relevant to the reason or reasons why the patient has undergone the CT
      examination. However, other findings may be incidental. The skin and SQ tissues
      are by definition on the periphery of CT images and may be overlooked by the
      radiologist, although findings related to them can be of clinical importance. The
      purpose of this pictorial essay is to present a broad spectrum of skin and
      subcutaneous findings which may be identified on CT examinations in the emergency
      setting (and in some cases nonemergently), and to briefly review the relevant
      imaging literature, which surprisingly is relatively limited on this topic.
      Categories of cutaneous and subcutaneous abnormalities that will be covered
      include trauma and hemorrhage, iatrogenic findings, infection, neoplasms,
      calcification, and other miscellaneous entities, all of which may initially
      present on emergency CT examinations of the body.

PMID- 23011051
TI  - Mild cognitive impairment as a predictor of falls in community-dwelling older
      people.
AB  - OBJECTIVE: : Incidence of falls in people with cognitive impairment with or
      without a formal diagnosis of dementia is estimated to be twice that of
      cognitively intact older adults. This study aimed to investigate whether mild
      cognitive impairment (MCI) is associated with falls in older people. DESIGN: :
      Prospective cohort study. SETTING: : Community sample, Sydney Memory and Ageing
      Study. PARTICIPANTS: : A total of 419 nondemented community-dwelling adults, age
      70-90 years. MEASUREMENTS: : A comprehensive neuropsychological test battery
      measuring four cognitive domains provided classification being with or without
      MCI on the basis of objective published criteria. Assessments of medical,
      physiologic, and psychological measures were also performed. Fallers were defined
      as people who had at least one injurious fall or at least two noninjurious falls
      during a 12-month follow-up period. RESULTS: : Of the participants, 342 (81.6%)
      had normal cognitive functioning, 58 (13.8%) had nonamnestic MCI, and 19 (4.5%)
      had amnestic MCI. People with MCI performed worse than people without MCI in
      measures of general health and balance. Logistic regression analyses showed that
      fall risk was significantly greater in people with MCI (odds ratio [OR]: 1.72,
      95% confidence interval [95% CI]: 1.03-2.89). This association was mainly
      apparent when the analysis was restricted to those with nonamnestic MCI (OR:
      1.98, 95% CI: 1.11-3.53), where the relationship was primarily explained by
      impaired executive functioning (OR: 1.27, 95% CI: 1.02-1.59). CONCLUSION: : The
      findings indicate that objectively defined MCI is an independent risk factor for
      injurious or multiple falls in a representative sample of community-dwelling
      older people. The presence of nonamnestic MCI, based primarily on executive
      function, was found to be an important factor in increasing fall risk.

PMID- 23011052
TI  - Quantification of anaesthetic effects on atrial fibrillation rate by partial
      least-squares.
AB  - The mechanism underlying atrial fibrillation (AF) remains poorly understood.
      Multiple wandering propagation wavelets drifting through both atria under
      hierarchical models are not understood. Some pharmacological drugs, known as
      antiarrhythmics, modify the cardiac ionic currents supporting the fibrillation
      process within the atria and may modify the AF propagation dynamics terminating
      the fibrillation process. Other medications, theoretically non-antiarrhythmic,
      may slightly affect the fibrillation process in non-defined mechanisms. We
      evaluated whether the most commonly used anaesthetic agent, propofol, affects AF
      patterns. Partial least-squares (PLS) analysis was performed to reduce
      significant noise into the main latent variables to find the differences between
      groups. The final results showed an excellent discrimination between groups with
      slow atrial activity during the propofol infusion.

PMID- 23011053
TI  - Psychometric Analysis of the Perceptions of Computerized Therapy Questionnaire
      Patient Version (PCTQ-P).
AB  - Dissemination and implementation science (DIS) in psychology is a growing area of
      research, with the potential to increase access to evidence based care. However,
      the field is characterized by a paucity of validated measures of DIS constructs.
      The present study aimed to fill this gap in the literature by examining the
      psychometric properties of the Perceptions of Computerized Therapy Questionnaire
      Patient Version (PCTQ-P), a self-report questionnaire for potential consumers
      based on Diffusion of Innovations theory. Undergraduate students participated in
      this two-study design, and were instructed to complete a battery of self-report
      measures, including the PCTQ-P. Internal consistency reliability, retest
      reliability, and discriminant validity were evaluated. Results provide evidence
      that the PCTQ-P is a psychometrically sound instrument for assessing potential
      consumers' perceptions of computer-based psychological treatments that are
      distinct from general help-seeking attitudes. With slight adaptation, the PCTQ-P
      can be used to examine other therapeutic modalities. Potential applications of
      the measure are discussed. 

PMID- 23011054
TI  - Alleviation of autophagy by knockdown of Beclin-1 enhances susceptibility of
      hippocampal neurons to proapoptotic signals induced by amino acid starvation.
AB  - Autophagy has been described as a cellular response to stressful stimuli like
      starvation. One of its primary functions is to recycle amino acids from degraded
      proteins for cellular survival under nutrient deprived conditions. Autophagy is
      characterized by double membrane cytosolic vesicles called autophagosomes and
      prolonged autophagy is known to result in autophagic (Type II) cell death. Beclin
      1 is involved in the regulation of autophagy in mammalian cells. This study
      examined the potential impact of knockdown of beclin-1 in an autophagic response
      in HT22 neurons challenged with amino acid starvation (AAS). AAS exposure induced
      light chain-3 (LC-3)-immunopositive and monodansylcadaverine (MDC) fluorescent
      dye-labeled autophagosome formation in cell bodies as early as 3 h post-AAS in
      wild type cells. Elevated levels of the autophagosome-targeting LC3-II were also
      observed following AAS. In addition, neuronal death induced by AAS in HT22-cells
      led to a moderate activation of caspase-3, a slight upregulation of AIF and did
      not alter the HtrA2 levels. Autophagy inhibition by a knockdown of beclin-1
      significantly reduced AAS-induced LC3-II increase, reduced accumulation of
      autophagosomes, and potentiated AAS-mediated neuronal death. Collectively, this
      study shows that the both apoptotic and autophagic machineries are inducible in
      cultured hippocampal HT22 neurons subjected to AAS. Our data further show that
      attenuation of autophagy by a knockdown of beclin-1 enhanced neurons
      susceptibility to proapoptotic signals induced by AAS and underlines that
      autophagy is per se a protective than a deleterious mechanism.

PMID- 23011055
TI  - Locking the phenyl rings of tetraphenylethene step by step: understanding the
      mechanism of aggregation-induced emission.
AB  - Stepwise locking of phenyl rings of tetraphenylethene increases the emission
      efficiency of luminogen solutions gradually, thus verifying the restriction of
      intramolecular rotation (RIR) mechanism of the aggregation induced emission
      phenomenon. The emission of the luminogen with one "O" bridge could be tuned
      reversibly in solid state through repeated heating and grinding.

PMID- 23011061
TI  - A phenomenological model for circadian and sleep allostatic modulation of plasma
      cortisol concentration.
AB  - Both circadian rhythmicity and sleep play significant roles in the regulation of
      plasma cortisol concentration by the hypothalamo-pituitary-adrenal (HPA) axis.
      Numerous studies have found links between sleep and changes in cortisol
      concentration, but the implications of these results have remained largely
      qualitative. In this article, we present a quantitative phenomenological model to
      describe the effects of different sleep durations on cortisol concentration. We
      constructed the proposed model by incorporating the circadian and sleep
      allostatic effects on cortisol concentration, the pulsatile nature of cortisol
      secretion, and cortisol's negative autoregulation of its own production and
      validated its performance on three study groups that experienced four distinct
      sleep durations. The model captured many disparate effects of sleep on cortisol
      dynamics, such as the inhibition of cortisol secretion after the wake-to-sleep
      transition and the rapid rise of cortisol concentration before morning awakening.
      Notably, the model reconciled the seemingly contradictory findings between
      studies that report an increase in cortisol concentration following total sleep
      deprivation and studies that report no change in concentration. This work
      provides a biomathematical approach to combine the results on the effects of
      sleep on cortisol concentration into a unified framework and predict the impact
      of varying sleep durations on the cortisol profile.

PMID- 23011060
TI  - Portal glucose delivery stimulates muscle but not liver protein metabolism.
AB  - Portal vein glucose delivery (the portal glucose signal) stimulates glucose
      uptake and glycogen storage by the liver, whereas portal amino acid (AA) delivery
      (the portal AA signal) induces an increase in protein synthesis by the liver.
      During a meal, both signals coexist and may interact. In this study, we compared
      the protein synthesis rates in the liver and muscle in response to portal or
      peripheral glucose infusion during intraportal infusion of a complete AA mixture.
      Dogs were surgically prepared with hepatic sampling catheters and flow probes.
      After a 42-h fast, they underwent a 3-h hyperinsulinemic (4* basal)
      hyperglucagonemic (3* basal) hyperglycemic (~160 mg/dl) hyperaminoacidemic
      (hepatic load 1.5* basal; delivered intraportally) clamp (postprandial
      conditions). Glucose was infused either via a peripheral (PeG; n = 7) or the
      portal vein (PoG; n = 8). Protein synthesis was assessed with a primed,
      continuous [(14)C]leucine infusion. Net hepatic glucose uptake was stimulated by
      portal glucose infusion (+1 mg.kg(-1).min(-1), P < 0.05) as expected, but hepatic
      fractional AA extraction and hepatic protein synthesis did not differ between
      groups. There was a lower arterial AA concentration in the PoG group (-19%, P <
      0.05) and a significant stimulation (+30%) of muscle protein synthesis associated
      with increased expression of LAT1 and ASCT2 AA transporters and p70S6
      phosphorylation. Concomitant portal glucose and AA delivery enhances skeletal
      muscle protein synthesis compared with peripheral glucose and portal AA delivery.
      These data suggest that enteral nutrition support may have an advantage over
      parenteral nutrition in stimulating muscle protein synthesis.

PMID- 23011062
TI  - Expression of genes involved in fatty acid transport and insulin signaling is
      altered by physical inactivity and exercise training in human skeletal muscle.
AB  - Physical deconditioning is associated with the development of chronic diseases,
      including type 2 diabetes and cardiovascular disease. Exercise training
      effectively counteracts these developments, but the underlying mechanisms are
      largely unknown. To gain more insight into these mechanisms, muscular gene
      expression levels were assessed after physical deconditioning and after exercise
      training of the lower limbs in humans by use of gene expression microarrays. To
      exclude systemic effects, we used human models for local physical inactivity (3
      wk of unilateral limb suspension) and for local exercise training (6 wk of
      functional electrical stimulation exercise of the extremely deconditioned legs of
      individuals with a spinal cord injury). The most interesting subset of genes,
      those downregulated after deconditioning as well as upregulated after exercise
      training, contained 18 genes related to both the "insulin action" and
      "adipocytokine signaling" pathway. Of these genes, the three with strongest
      up/downregulation were the muscular fatty acid-binding protein-3 (FABP3), the
      fatty acid oxidizing enzyme hydroxyacyl-CoA dehydrogenase (HADH), and the
      mitochondrial fatty acid transporter solute carrier 25 family member A20
      (SLC25A20). The expression levels of these genes were confirmed using RT-qPCR.
      The results of the present study indicate an important role for a decreased
      transport and metabolism of fatty acids, which provides a link between physical
      activity levels and insulin signaling.

PMID- 23011063
TI  - Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in
      primary skeletal muscles and adipocytes and impairs glucose homeostasis.
AB  - Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to
      glucose homeostasis and is mediated by regulating glucose transporter GLUT4
      subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4
      intracellular retention and release to the cell surface and consequently
      regulates glucose uptake into cells. To determine AS160 function in GLUT4
      trafficking in primary skeletal muscles and adipocytes and investigate its role
      in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We
      observed increased and normal basal glucose uptake in isolated AS160(-/-)
      adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was
      impaired and GLUT4 expression decreased in both. No such abnormalities were found
      in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes
      isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative
      GLUT4 levels were increased under basal conditions and remained the same after
      insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4,
      determined with a glucose transporter photoaffinity label, were increased in
      AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions.
      Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest
      that AS160 is essential for GLUT4 intracellular retention and regulation of
      glucose uptake in adipocytes and skeletal muscles in which it is normally
      expressed. In vivo studies revealed impaired insulin tolerance in the presence of
      normal (male) and impaired (female) glucose tolerance. Concurrently, insulin
      elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal
      muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a
      target for differential manipulation of glucose homeostasis.

PMID- 23011064
TI  - Differential modulation of gonadotropin responses to kisspeptin by
      aminoacidergic, peptidergic, and nitric oxide neurotransmission.
AB  - Kisspeptins (Kp), products of the Kiss1 gene, have emerged as essential elements
      in the control of GnRH neurons and gonadotropic secretion. However, despite
      considerable progress in the field, to date limited attention has been paid to
      elucidate the potential interactions of Kp with other neurotransmitters known to
      centrally regulate the gonadotropic axis. We characterize herein the impact of
      manipulations of key aminoacidergic (glutamate and GABA), peptidergic (NKB, Dyn,
      and MCH), and gaseous [nitric oxide (NO)] neurotransmission on gonadotropin
      responses to Kp-10 in male rats. Blockade of ionotropic glutamate receptors (of
      the NMDA and non-NMDA type) variably decreased LH responses to Kp-10, whereas
      activation of both ionotropic and metabotropic receptors, which enhanced LH and
      FSH release per se, failed to further increase gonadotropin responses to Kp-10.
      In fact, coactivation of metabotropic receptors attenuated LH and FSH responses
      to Kp-10. Selective activation of GABA(A) receptors decreased Kp-induced
      gonadotropin secretion, whereas their blockade elicited robust LH and FSH bursts
      and protracted responses to Kp-10 when combined with GABA(B) receptor inhibition.
      Blockade of Dyn signaling (at kappa-opioid receptors) enhanced LH responses to Kp
      10, whereas activation of Dyn and NKB signaling modestly reduced Kp-induced LH
      and FSH release. Finally, MCH decreased basal LH secretion and modestly reduced
      FSH responses to Kp-10, whereas LH responses to Kp-10 were protracted after
      inhibition of NO synthesis. In summary, we present herein evidence for the
      putative roles of glutamate, GABA, Dyn, NKB, MCH, and NO in modulating
      gonadotropic responses to Kp in male rats. Our pharmacological data will help to
      characterize the central interactions and putative hierarchy of key
      neuroendocrine pathways involved in the control of the gonadotropic axis.

PMID- 23011059
TI  - Arginine de novo and nitric oxide production in disease states.
AB  - Arginine is derived from dietary protein intake, body protein breakdown, or
      endogenous de novo arginine production. The latter may be linked to the
      availability of citrulline, which is the immediate precursor of arginine and
      limiting factor for de novo arginine production. Arginine metabolism is highly
      compartmentalized due to the expression of the enzymes involved in arginine
      metabolism in various organs. A small fraction of arginine enters the NO synthase
      (NOS) pathway. Tetrahydrobiopterin (BH4) is an essential and rate-limiting
      cofactor for the production of NO. Depletion of BH4 in oxidative-stressed
      endothelial cells can result in so-called NOS3 "uncoupling," resulting in
      production of superoxide instead of NO. Moreover, distribution of arginine
      between intracellular transporters and arginine-converting enzymes, as well as
      between the arginine-converting and arginine-synthesizing enzymes, determines the
      metabolic fate of arginine. Alternatively, NO can be derived from conversion of
      nitrite. Reduced arginine availability stemming from reduced de novo production
      and elevated arginase activity have been reported in various conditions of acute
      and chronic stress, which are often characterized by increased NOS2 and reduced
      NOS3 activity. Cardiovascular and pulmonary disorders such as atherosclerosis,
      diabetes, hypercholesterolemia, ischemic heart disease, and hypertension are
      characterized by NOS3 uncoupling. Therapeutic applications to influence (de novo)
      arginine and NO metabolism aim at increasing substrate availability or at
      influencing the metabolic fate of specific pathways related to NO bioavailability
      and prevention of NOS3 uncoupling. These include supplementation of arginine or
      citrulline, provision of NO donors including inhaled NO and nitrite (sources),
      NOS3 modulating agents, or the targeting of endogenous NOS inhibitors like
      asymmetric dimethylarginine.

PMID- 23011065
TI  - Suppression in growth hormone during overeating ameliorates the increase in
      insulin resistance and cardiovascular disease risk.
AB  - Previously, we reported that overeating for only a few days markedly suppressed
      the secretion of growth hormone (GH). The purpose of the present study was to
      determine the role of this reduction in GH concentration on key metabolic
      adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults
      were admitted to the hospital for 2 wk, during which time they ate ~4,000
      kcal/day (70 kcal.kg fat-free mass(-1).day(-1); 50% carbohydrate, 35% fat, and
      15% protein), and their plasma GH concentration was allowed to decline naturally
      (control). An additional eight subjects underwent the same overeating
      intervention and received exogenous GH treatment (GHT) administered in four daily
      injections to mimic physiological GH secretion throughout the 2-wk overeating
      period. We measured plasma insulin and glucose concentrations in the fasting and
      postprandial state as well as fasting lipolytic rate, proteolytic rate, and
      fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT
      prevented the fall in plasma GH concentration, maintaining plasma GH
      concentration at baseline levels (1.2 +/- 0.2 ng/ml), which increased fasting and
      postprandial assessments of insulin resistance (P < 0.05) and increased fasting
      lipidemia (all P < 0.05 vs. control). In addition, preventing the suppression in
      GH with overeating also blunted the increase in systemic proteolysis (P < 0.05
      GHT vs. control). However, GHT did not alter lipolysis or FSR in response to
      overeating. In conclusion, our main findings suggest that the suppression in GH
      secretion that naturally occurs during the early stages of overeating may help
      attenuate the insulin resistance and hyperlipidemia that typically accompany
      overeating.

PMID- 23011066
TI  - Application of diagnosis-related groups (DRGs).

PMID- 23011067
TI  - Potentially preventable events:  an actionable set of measures for linking
      quality improvement and cost savings.
AB  - Rising health care costs will result in reduced payments to providers, but across
      the-board provider payment reductions are not the answer. Instead, existing
      payment systems should be reformed to strengthen value for the dollars spent.
      This can be accomplished by increasing efficiency, improving quality and
      outcomes, and lowering costs. Payment system reforms must be practical,
      transparent, identify opportunities for care improvement, and demonstrate
      material cost savings. Most importantly, because the current growth in health
      care costs is unsustainable, these reforms must be able to be implemented today.
      A set of comprehensive measures is being used by state government and private
      payers in the United States to adjust payment, based on improved outcomes
      quality. This article details the use of this set of measures, referred to as
      potentially preventable events, and demonstrates how they are being applied to
      achieve health care value.

PMID- 23011068
TI  - Cost and quality implications of discrepancies between admitting and discharge
      diagnoses.
AB  - BACKGROUND: Presenting and discharge diagnoses of hospitalized patients may
      differ as a result of patient complexity, diagnostic dilemmas, or errors in
      clinical judgment at the time of primary assessment. When diagnoses at admission
      and discharge are not in agreement, this discrepancy may indicate more complex
      processes of care and resultant costs. It is unclear whether surrogate measures
      reflecting quality of care are impacted by discrepant diagnoses. OBJECTIVE: To
      assess whether an association exists between admitting and discharge
      International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes
      and other quality markers including hospital length of stay, total cost of care,
      and 30-day readmission rate. METHODS: This was a retrospective, cross-sectional
      analysis of general internal medicine patients aged 18 years and older. Diagnosis
      discrepancy was defined as a difference between the 3-digit ICD-9 diagnosis code
      at admission and the principal 3-digit ICD-9 diagnosis code at discharge.
      RESULTS: Sixty-eight percent of patients had a diagnosis discrepancy. Diagnosis
      discrepancy was associated with a 0.41-day increase in length of stay (P < .001),
      $663 increase in direct costs (P < .001), and a 1.55 times greater odds of
      readmission within 30 days (P < .001). CONCLUSION: Diagnosis discrepancy was
      associated with hospital quality outcome measures. This finding likely reflects
      variations in patients' diagnostic complexity.

PMID- 23011069
TI  - Avoidable after-hours calls to physicians in family medicine.
AB  - OBJECTIVES: To assess avoidability in after-hours telephone calls. Identification
      of predictors of avoidable calls is necessary so that system changes can be
      implemented in the interest of efficiency in patient care. BACKGROUND: A new
      after-hours family physician call service was established in a large group
      practice to replace some of the resident call shifts and meet patient
      expectations. DATA SOURCE: Call logs completed by physicians who were on call.
      SAMPLE: A total of 131 completed after-hours calls. AVOIDABLE CALL: An after
      hours call to a physician that could have been effectively handled by another
      person, by a communication mechanism, or at another time. ASSESSMENT RESULT: Call
      defined as avoidable or not avoidable as assessed by the physician on call.
      SURVEY RESULTS: Less than half (41.9%) of calls were avoidable. Run charts failed
      tests for shifts and runs. Patient age, time of day, and day of the week were not
      related to being avoidable, but avoidability varied by physician (P = .003).
      CONCLUSION: The after-hours call service experienced high rates of avoidable
      calls. Avoidability was associated with the physician on call. Reducing avoidable
      after-hours calls to physicians will require building clinical consensus on which
      types of calls should be considered avoidable and how avoidable calls should be
      redirected.

PMID- 23011070
TI  - Use of computer alerts to prevent the inappropriate use of metformin in an
      inpatient setting.
AB  - BACKGROUND: Metformin is recommended as initial therapy for most patients with
      type 2 diabetes mellitus. Its most serious adverse effect, lactic acidosis, is a
      rare entity with a high mortality rate. Despite well-publicized
      contraindications, metformin is inappropriately prescribed to many hospitalized
      patients. OBJECTIVE: To determine the efficacy of computer alerts at reducing
      inappropriate metformin prescribing. METHODS: Retrospective chart review of all
      hospitalized patients who received an order for metformin, before (n = 144) and
      after (n = 147) an intervention designed to reduce inappropriate administration.
      This intervention included 2 "hard-stop" computer alerts that prevented
      prescribing metformin to patients with renal dysfunction and in critical care or
      postoperative units; and 2 "soft" alerts that fired when no serum creatinine was
      available or the patient was in an outpatient surgical unit. Charts were reviewed
      for the presence of contraindications: renal insufficiency, congestive heart
      failure, recent myocardial infarction, surgery, or intravenous contrast use
      within 48 hours of metformin administration. RESULTS: In the preintervention
      group there were 47 violations compared with 13 violations in the
      postintervention group (P < .001). The greatest improvement was in surgical
      patients (39 violations vs 11, P < .001). CONCLUSIONS: Computer alerts at order
      entry were effective in decreasing the inappropriate prescribing of metformin in
      an inpatient setting.

PMID- 23011071
TI  - Sustainability in primary care and Mental Health Integration projects in Veterans
      Health Administration.
AB  - OBJECTIVE: To explore staff perceptions about sustainability, commitment to
      change, participation in change process, and information received about the
      change project within the Veterans Administration Primary Care and Mental Health
      Integration (PC-MHI) initiative and to examine differences from the Veterans
      Health Administration Mental Health Systems Redesign (MHSR) initiative. DATA
      SOURCES: Surveys of change team members involved in the Veterans Affairs PC-MHI
      and MHSR initiatives. STUDY DESIGN: One-way analysis of variance examined the
      relationship between commitment, participation and information, and
      sustainability. Differences in PC-MHI sustainability were explored by location
      and job classification. Staff sustainability perceptions were compared with MHSR
      results. PRINCIPAL FINDINGS: Sustainability differed by staff discipline.
      Difference between MHSR and PC-MHI existed by job function and perceptions about
      the change benefits. Participation in the change process and information received
      about the change process were positively correlated with sustainability. Staff
      commitment to change was positively associated with staff perceptions about the
      benefits of change and staff attitudes toward change. CONCLUSIONS: Sustainability
      is an important part of organizational change efforts. Change complexity seems to
      influence perception about sustainability and impacts staff perceptions about the
      benefits of change. These perceptions seem to be driven by the information
      received and opportunities to participate in the change process. Further research
      is needed to understand how information and participation influence
      sustainability and affect employee commitment to change.

PMID- 23011072
TI  - Postreferral colonoscopy delays in diagnosis of colorectal cancer:  a mixed
      methods analysis.
AB  - BACKGROUND: Delays in diagnosis of colorectal cancer (CRC) are one of the most
      common reasons for malpractice claims and lead to poor outcomes. However, they
      are not well studied. AIMS: We used a mixed quantitative-qualitative approach to
      analyze postreferral colonoscopy delays in CRC patients and explored referring
      physician's perception of processes surrounding these delays. METHODS: Two
      physician-raters conducted independent electronic health record reviews of new
      CRC cases in a large integrated safety-net system to determine postreferral
      colonoscopy delays, which we defined as failures to perform colonoscopy within 60
      days of referral for an established indication(s). To explore perceptions of
      colonoscopy processes, we conducted semistructured interviews with a sample of
      primary care physicians (PCPs) and used a content analysis approach. RESULTS: Of
      104 CRC cases that met inclusion criteria, reviewers agreed on the presence of
      postreferral colonoscopy delays in 35 (33.7%) cases; kappa = 0.99 (95% CI, 0.83
      0.99). The median time between first referral and completion of colonoscopy was
      123.0 days (range 62.0-938.0; interquartile range = 90.0 days). In about two
      thirds of instances (64.8%), the reason for delay was a delayed future
      appointment with the gastroenterology service. On interviews, PCPs attributed
      long delays in scheduling to reduced endoscopic capacity and inefficient
      processes related to colonoscopy referral and scheduling, including considerable
      ambiguity regarding referral guidelines. Many suggested that navigation models be
      applied to streamline CRC diagnosis. CONCLUSION: Postreferral delays in CRC
      diagnosis are potentially preventable. A comprehensive mixed-methods methodology
      might be useful for others to identify the steps in the diagnostic process that
      are in most need for improvement.

PMID- 23011073
TI  - Impact of 5 years of lean six sigma in a University Medical Center.
AB  - Lean Six Sigma (LSS) is an originally industry-based methodology for cost
      reduction and quality improvement. In more recent years, LSS was introduced in
      health care as well. This article describes the experiences of the University
      Medical Center Groningen, the second largest hospital in the Netherlands, with
      LSS. It was introduced in 2007 to create the financial possibility to develop
      innovations. In this article, we describe how LSS was introduced, and how it
      developed in the following years. We zoom in at the traumatology department,
      where all main processes have been analyzed and improved. An evaluation after 5
      years shows that LSS helped indeed reducing cost and improving quality. Moreover,
      it aided the transition of the organization from purely problem oriented to more
      process oriented, which in turn is helpful in eliminating waste and finding
      solutions for difficult problems. A major benefit of the program is that own
      employees are trained to become project leaders for improvement. Several people
      from the primary process were thus stimulated and equipped to become role models
      for continuous improvement.

PMID- 23011074
TI  - Digital video recording in the inpatient setting:  a tool for improving care
      experiences and efficiency while decreasing waste and cost.
AB  - The need to significantly improve patient centeredness and efficiency, while
      reducing waste and cost, in health care is an area of focus for health policy
      leaders. We employed digital video recording on a postsurgical inpatient unit as
      a method of understanding care delivery through the eyes of patients, families,
      and caregivers. Key findings of the study included identification of the total
      number of staff (by function)-to-patient contacts and the percentage of time
      patients spent in their room during recovey. The use of digital video recording
      eliminated the impracticality of real-time observation in the inpatient setting
      and should be considered as a tool for helping to achieve necessary
      transformation in care delivery.

PMID- 23011075
TI  - Differential case reporting in a national clinical quality database:  an analysis
      of the impact on comparison of outcome between departments.
AB  - INTRODUCTION: Selection biases due to difference in reporting may cause spurious
      findings. The purpose of this study was to illustrate the effect of case
      incompleteness on the differences in 180-day survival rate when comparing
      departments. METHODS: Completeness was estimated as the proportion of patients
      reported to the Danish Lymphoma Database compared with the National Patient
      Registry. The effect of differential reporting between departments was
      investigated using plots were the proportion of patients who survived 180 days in
      the individual departments were compared with the national average as well as
      examining the association between the department and 180-day survival. RESULTS:
      In total, 8015 patients were registered in the National Patient Registry with a
      lymphoma diagnosis. Of these, 1824 patients were not reported to the Danish
      Lymphoma database equaling a rate of completion of 77.2%. There were large
      differences between departments with regard to patient completeness (range, 52.4%
      91.6%). The survival of the patients reported to the database was significantly
      better than those not reported and the differential reporting affected the
      department ranking. CONCLUSION: Differential case reporting may cause spurious
      findings. To ensure valid conclusions validation against a gold standard and
      continuous feedback to data providers is important.

PMID- 23011078
TI  - Ectopic expression of a fruit phytoene synthase from Citrus paradisi Macf.
      promotes abiotic stress tolerance in transgenic tobacco.
AB  - Abscisic acid (ABA) is an important regulator of plant responses to environmental
      stresses and an absolute requirement for stress tolerance. Recently, a third
      phytoene synthase (PSY3) gene paralog was identified in monocots and demonstrated
      to play a specialized role in stress-induced ABA formation, thus suggesting that
      the first committed step in carotenogenesis is a key limiting step in ABA
      biosynthesis. To examine whether the ectopic expression of PSY, other than PSY3,
      would similarly affect ABA level and stress tolerance, we have produced
      transgenic tobacco containing a fruit-specific PSY (CpPSY) of grapefruit (Citrus
      paradisi Macf.). The transgenic plants contained a single- or double-locus
      insertion and expressed CpPSY at varying transcript levels. In comparison with
      the wild-type plants, the CpPSY expressing transgenic plants showed a significant
      increase on root length and shoot biomass under PEG-, NaCl- and mannitol-induced
      osmotic stress. The enhanced stress tolerance of transgenic plants was correlated
      with the increased endogenous ABA level and expression of stress-responsive
      genes, which in turn was correlated with the CpPSY copy number and expression
      level in different transgenic lines. Collectively, these results provide further
      evidence that PSY is a key enzyme regulating ABA biosynthesis and that the
      altered expression of other PSYs in transgenic plants may provide a similar
      function to that of the monocot's PSY3 in ABA biosynthesis and stress tolerance.
      The results also pave the way for further use of CpPSY, as well as other PSYs, as
      potential candidate genes for engineering tolerance to drought and salt stress in
      crop plants.

PMID- 23011079
TI  - Computerized detection and recognition of follicles in ovarian ultrasound images:
      a review.
AB  - Observing changes in females' ovaries is essential in obstetrics and
      gynaecological imaging, e.g., genetic engineering and human reproduction. It is
      particularly important to monitor the dynamics of ovarian follicles' growth, as
      only fully mature and grown follicles, i.e., the dominant follicles have a
      potential to ovulate at the end of a follicular phase. Gynaecologists follow this
      process in two dimensions, but recently three-dimensional (3-D) ultrasound
      examinations are coming to the fore. This paper surveys the existing computer
      methods for detection, recognition, and analyses of follicles in two-dimensional
      (2-D) and 3-D ovarian ultrasound recordings. Our study focuses on the efficiency,
      validation, and assessment of proposed follicle processing algorithms. The most
      important processing steps were identified in order to compare their
      performances. Higher ranking solutions are suggested for the so-called best
      algorithm for 2-D and 3-D ultrasound recordings of ovarian follicles. Finally,
      some guidelines for future research in this field are discussed, in particular
      for 3-D ultrasound volumes.

PMID- 23011080
TI  - Fluctuation analysis of respiratory impedance waveform in asthmatic patients:
      effect of airway obstruction.
AB  - Fluctuation analysis has great potential to contribute to pulmonary clinical
      science and practice. We evaluated the relationship between asthma and the
      respiratory impedance recurrence period density entropy (RPDEnZrs) and the
      variability (SDZrs). A non-invasive and simple protocol for assessing respiratory
      mechanics during spontaneous breathing was used in a group of 74 subjects with
      various levels of airway obstruction. Airway obstruction resulted in a reduction
      in the RPDEnZrs that was significantly correlated with both spirometric indices
      of airway obstruction (R = 0.48, p < 0.0001) and mean respiratory impedance (R = 
      0.83, p < 0.0001). These results suggest that the impedance pattern becomes less
      complex in asthmatic patients, which may explain the reduction in respiratory
      systems' adaptability to daily life activities. Preliminary evaluations indicate
      that RPDEnZrs may contribute to the asthma diagnosis, presenting accuracies of 82
      and 87 % in patients with moderate and severe airway obstruction, respectively.
      On the other hand, SDZrs increased with obstruction (p < 0.0001) and was
      inversely correlated with spirometric indices of obstruction (R = -0.42, p =
      0.0003) and directly associated with mean impedance (R = 0.88, p < 0.0001). This
      analysis contributes to elucidate previous studies and identified respiratory
      changes in patients with moderate and severe obstruction with an adequate
      accuracy (85 and 87 %, respectively).

PMID- 23011081
TI  - Bortezomib induces tumor-specific cell death and growth inhibition in
      hepatocellular carcinoma and improves liver fibrosis.
AB  - BACKGROUND: Human hepatocellular carcinoma (HCC) is highly ubiquitinated. The
      ubiquitination is important to the generatation of HCC. The antitumor and
      antifibrosis effects of an ubiquitin-proteasome system inhibitor, bortezomib, on
      HCC with liver cirrhosis (LC) were analyzed in vitro and in vivo. METHODS: The
      effect of bortezomib was analyzed in the rat hepatocarcinogenesis model using a
      DEN and CDAA diet (DEN/CDAA model), which shows severe LC and generation of HCC.
      The decrease of GST-P-positive foci and HCC were analyzed in vivo. Cell death was
      analyzed by cell death detection kit. Liver fibrosis was checked by sirius-red
      staining and alpha-smooth muscle actin staining. The in vitro study involved 3
      HCC cell lines (HepG2, HuH7, and HLF) and primary rat and human hepatocytes. The
      proliferation rate of the HCC cell line was analyzed using the MTT assay and FACS
      analysis. The toxicity of bortezomib was checked using the LDH release assay for
      primary human and rat hepatocytes. RESULTS: In the rat hepatocarcinogenesis
      model, bortezomib prevented the development of preneoplastic lesions during the
      early stages of hepatocarcinogenesis and specifically induced cell death in HCC.
      Furthermore, bortezomib inhibited cell proliferation and induced tumor-specific
      cell death in HCC cell lines with decrease of cyclin D1 and phospho-Rb
      expression. Further, bortezomib showed no hepatotoxicity of primary rat and human
      hepatocytes, suggesting that it might be an HCC-specific drug. Bortezomib also
      prevented the activation of hepatic stellate cells and inhibited the liver
      fibrosis of the DEN/CDAA model. CONCLUSIONS: Bortezomib appears to be an ideal
      target drug for HCC with LC.

PMID- 23011083
TI  - Combinations of simple baseline variables accurately predict sustained
      virological response in patients with recurrent hepatitis C after liver
      transplantation.
AB  - BACKGROUND: The efficacy of antiviral therapy in patients with hepatitis C
      recurrence after liver transplantation (LT) is far from optimal and a careful
      selection of candidates with the best chances to achieve sustained virological
      response (SVR) is relevant. Moreover, investigating the effects of sustained
      viral clearance on clinical outcomes is particularly significant. We aimed to
      identify and combine the best baseline predictors of SVR and to assess the
      clinical outcomes of antiviral therapy after LT. METHODS: We studied 144
      hepatitis C virus (HCV)-infected LT recipients who underwent antiviral therapy
      following transplantation. Baseline predictors of SVR including donor and
      recipient interleukin IL28B (IL28B) rs12979860 genotype were evaluated, and the
      long-term effects of antiviral therapy on clinical outcomes were assessed.
      RESULTS: The presence of an IL28B CC genotype with either low viral load (VL),
      young donor age, or cyclosporine A (CsA)-based immunosuppression identified
      individuals with 69-80 % probabilities of SVR. In contrast, only 20% of
      recipients with a CT/TT IL28B genotype and either high VL, old donor age, or non
      CsA immunosuppression achieved an SVR (p = 0.004). Regarding clinical outcomes,
      the 5-year cumulative probability of graft loss was 2% for the SVR patients and
      48% for non-responders (p < 0.001). CONCLUSIONS: The use of simple combinations
      of baseline variables including IL28B polymorphisms identifies HCV-infected LT
      recipients with different probabilities of response to antiviral treatment. SVR
      is associated with improved clinical outcomes.

PMID- 23011082
TI  - Kinetics of peripheral hepatitis B virus-specific CD8+ T cells in patients with
      onset of viral reactivation.
AB  - BACKGROUND: Patients with resolved hepatitis B virus (HBV) infection undergoing
      chemotherapy or immunosuppressive therapy are potentially at risk of HBV
      reactivation. However, it remains unclear how liver disease develops after HBV
      reactivation. To compare the host immune response against HBV, we performed
      immunological analyses of six HBV reactivation patients. METHODS: The numbers of
      peripheral HBV-specific CD8+ T cells were investigated longitudinally in six HLA
      A2- and/or A24-positive patients with HBV reactivation. In addition, 34 patients
      with resolved HBV, 17 patients with inactive chronic hepatitis B (ICHB), 17
      patients with chronic hepatitis B (CHB) and 12 healthy controls were analyzed.
      The number and function of HBV-specific CD8+ T cells were assessed by flow
      cytometry using tetramer staining and intracellular IFN-gamma production.
      Furthermore, the numbers of CD4+ CD25+ or CD4+ Foxp3+ T cells and serum
      inflammatory cytokine levels were analyzed. RESULTS: The frequency of HBV
      specific CD8+ T cells was significantly increased in HBV reactivation patients
      compared with ICHB and CHB patients. In addition, the number of HBV-specific CD8+
      T cells was increased in resolved HBV patients compared with ICHB patients. PD-1
      expression was decreased in HBV reactivation patients compared with ICHB and CHB
      patients. The numbers of HBV-specific CD8+ T cells and CD4+ CD25+ or CD4+ Foxp3+
      T cells were negatively correlated following onset of HBV reactivation.
      CONCLUSIONS: During HBV reactivation, the frequency of HBV-specific CD8+ T cells
      increased even though the administration of immunosuppressive drugs and
      interactions with CD4+ regulatory T cells may be important for the onset of liver
      disease.

PMID- 23011084
TI  - Soluble CD163 serum levels are elevated and correlated with IL-12 and CXCL10 in
      patients with long-standing rheumatoid arthritis.
AB  - CD163, a membrane glycoprotein restricted to monocyte-macrophage cell lineage, is
      released in the terminal phase of acute inflammation and during chronic
      inflammation, with anti-inflammatory and antiangiogenic role. The proteolytically
      detached ectodomain of CD163 is the soluble component sCD163. A few studies were
      performed regarding circulating sCD163 in human diseases. Only two were
      accomplished in patients with rheumatoid arthritis (RA). Our concern was (1) to
      evaluate sCD163 serum concentrations in active RA patients with long-standing
      evolution, (2) to correlate them with clinical parameters, laboratory markers,
      disease activity, and (3) to search possible relationships with some cytokines
      (IL-12, IL-17) and chemokine (CXCL10), involved in RA pathogenesis. First and
      third topics were not achieved until now, and the second one points out
      discordant findings and unspecified aspects. It was achieved immunoassay of serum
      sCD163, IL-12, IL-17, CXCL10 and traditional methods for RA laboratory markers.
      The mean sCD163 level of 33 patients was significantly higher than in 20 normal
      controls (p = 0.0001), 59.3 % of them with concentrations above normal cut-off
      value. sCD163 levels were weakly correlated with CRP and RF but not with ERS and
      disease activity. IL-12 and CXCL10 serum levels strongly correlated with sCD163
      concentrations, while IL-17 positively but insignificantly correlated. In
      conclusion, serum sCD163 levels are significantly elevated in long-standing RA
      patients, but sCD163 has no role as a biomarker of disease activity. High
      correlation of sCD163 with IL-12 and CXCL10 suggests the association of their
      well-known anti-inflammatory function in long-standing RA patients.

PMID- 23011085
TI  - Does vasculitis alone cause AVN? A review of literature.
AB  - AVN is caused by a disease, or severe trauma that affects the blood supply to the
      bone or in many cases may be idiopathic, with no known cause. AVN pathophysiology
      is most closely linked to SLE literature, and there is a strong cause and effect
      relationship between corticosteroid intake and AVN development in SLE patients,
      and AVN is extremely rare in the absence of steroid use. Apart from few anecdotal
      reports, there is no data on exact pathophysiologic mechanisms responsible for
      AVN in the setting of vasculitis. We saw a 69-year-old man with femoral AVN and a
      possibility of vasculitis as the underlying cause was raised by the radiologist,
      and hence we present this literature search on vasculitis per se causing AVN of
      the bone. 

PMID- 23011086
TI  - Valentin dancing at the Moulin Rouge: a very good depiction of joint
      hypermobility by Toulouse-Lautrec.

PMID- 23011087
TI  - Intra-muscular arteries are also affected in Takayasu's arteritis.
AB  - Takayasu's arteritis (TA) is a chronic vasculitis, primarily affecting large
      vessels, such as the aorta and its main branches. Several reports suggest that
      the vascular inflammatory process is not always confined to large vessels. Here,
      a new case of vasculitis in intra-muscular arteries associated with TA is
      reported. This case provides further support for the idea that TA also involves
      small arterial vessels. 

PMID- 23011089
TI  - The effect of anti-tuberculosis treatment on levels of anti-phospholipid and anti
      neutrophil cytoplasmatic antibodies in patients with active tuberculosis.
AB  - The aim of this study is to determine the prevalence and effect of anti
      tuberculosis treatment on anti-phospholipid antibodies and anti-neutrophil
      cytoplasmatic antibodies (ANCA) in patients with active mycobacterial infections.
      Thirty-three consecutive patients (age 56 years, 26 males) with recently
      diagnosed active tuberculosis (TB) were enrolled. Data included clinical disease
      features, symptom duration, multidrug resistance and presence of HIV. Serum
      samples taken before and after TB treatment were frozen at -20  degrees C and
      tested for anti-cardiolipin IgG (aCL), anti-beta2 glycoprotein IgG (anti
      beta2GPI), anti-prothrombin, anti-proteinase 3 (PR3), myeloperoxidase (MPO),
      bactericidal/permeability (BPI) and lactoferrin. Thirty percent of patients had
      higher than cut-off value for anti-beta2GPI, and 9 % had increased aCL. The
      levels of antibodies against beta2GPI and aCL normalized post-treatment. A
      substantial proportion of patients had high baseline anti-PR3, MPO, BPI and
      lactoferrin levels. Most anti-lactoferrin and anti-MPO levels decreased post
      treatment, while anti-PR3 increased in most of the baseline-positive patients.
      Some patients had de novo anti-PR3 and MPO formation after 6-month treatment.
      Patients with active TB have significantly increased anti-beta2GPI and ANCA
      titers. While anti-beta2GPI titers normalize post-treatment, ANCA behave in a
      complex way. Anti-TB treatment may induce normalization of anti-lactoferrin and
      anti-MPO, and de novo anti-PR3 and MPO formation.

PMID- 23011090
TI  - Impact of sphingosine kinase 2 deficiency on the development of TNF-alpha-induced
      inflammatory arthritis.
AB  - Sphingolipids are components of the plasma membrane whose metabolic manipulation
      is of interest as a potential therapeutic approach in a number of diseases.
      Sphingosine kinase 1 (SphK1), the major kinase that phosphorylates sphingosine to
      sphingosine-1-phosphate (S1P), was previously shown by our group and others to
      modulate inflammation in murine models of inflammatory arthritis, inflammatory
      bowel disease and asthma. Sphingosine kinase 2's (SphK2) impact on inflammation
      is less well known, as variable results were reported depending on the disease
      model. A specific SphK2 inhibitor inhibited inflammatory arthritis in one model,
      while siRNA knockdown of SphK2 worsened arthritis in another. We previously
      demonstrated that SphK1 deficient mice are protected against development of hTNF
      alpha-induced arthritis. To investigate the role of SphK2 in TNF-alpha-induced
      arthritis, we developed SphK2 deficient hTNF-alpha overexpressing mice and
      separately treated hTNF-alpha mice with ABC294640, a SphK2-specific inhibitor.
      Our data show that genetic inhibition of SphK2 did not significantly impact the
      severity or progression of inflammatory arthritis, while pharmacologic inhibition
      of SphK2 led to significantly more severe arthritis. Compared to vehicle-treated
      mice, ABC294640 treated mice also had less S1P in whole blood and inflamed joint
      tissue, although the differences were not significant. ABC294640 treatment did
      not affect SphK1 activity in the inflamed joint while little SphK2 activity was
      detected in the joint. We conclude that the differences in the inflammatory
      phenotype in genetic inhibition versus pharmacologic inhibition of SphK2 can be
      attributed to the amount of ABC294640 used in the experiments versus the impact
      of acute inhibition of SphK2 with ABC294640 versus genetically induced life-long
      SphK2 deficiency. Thus, inhibition of SphK2 appears to be proinflammatory in
      contrast to the clear anti-inflammatory effects of blocking SphK1. Therapies
      directed at this sphingosine kinase pathways will need to be specific in their
      targeting of sphingosine kinases.

PMID- 23011088
TI  - Scleroderma therapy: clinical overview of current trends and future perspective.
AB  - Systemic sclerosis is a chronic autoimmune condition with a complex pathogenesis
      and a high rate of mortality and morbidity. Internal organ involvement requires
      interdisciplinary approach in individual patient management. New discoveries in
      the pathogenesis of scleroderma herald a drastic change in the traditional
      outlook to therapy and have led to the development of the target-based approach
      in management. The challenge at present is to translate these advances in
      molecular mechanisms into well-designed clinical trials that will recognize
      potential disease-modifying therapies. This article is an evidence-based review
      of prevailing treatment options and future therapeutic targets in systemic
      sclerosis.

PMID- 23011092
TI  - Strong positive associations between seafood, vegetables, and alcohol with blood
      mercury and urinary arsenic levels in the Korean adult population.
AB  - Blood mercury and urinary arsenic levels are more than fivefold greater in the
      Korean population compared with those of the United States. This may be related
      to the foods people consumed. Therefore, we examined the associations between
      food categories and mercury and arsenic exposure in the Korean adult population.
      Data regarding nutritional, biochemical, and health-related parameters were
      obtained from a cross-sectional study, the 2008-2009 Korean National Health and
      Nutrition Examination Survey (3,404 men and women age >= 20 years). The log
      transformed blood mercury and urinary arsenic levels were regressed against the
      frequency tertiles of each food group after covariate adjustment for sex, age,
      residence area, education level, smoking status, and drinking status using food
      frequency data. Blood mercury levels in the high consumption groups compared to
      the low consumption groups were elevated by about 20 percents with salted fish,
      shellfish, whitefish, bluefish, and alcohol, and by about 9-14 percents with
      seaweeds, green vegetables, fruits and tea, whereas rice did not affect blood
      mercury levels. Urinary arsenic levels were markedly increased with consumption
      of rice, bluefish, salted fish, shellfish, whitefish, and seaweed, whereas they
      were moderately increased with consumption of grains, green and white vegetables,
      fruits, coffee, and alcohol. The remaining food categories tended to lower these
      levels only minimally. In conclusion, the typical Asian diet, which is high in
      rice, salted fish, shellfish, vegetables, alcoholic beverages, and tea, may be
      associated with greater blood mercury and urinary arsenic levels. This study
      suggests that mercury and arsenic contents should be monitored and controlled in
      soil and water used for agriculture to decrease health risks from heavy-metal
      contamination.

PMID- 23011093
TI  - Diameter-controlled synthesis of alpha-Mn2O3 nanorods and nanowires with enhanced
      surface morphology and optical properties.
AB  - Single crystalline alpha-Mn(2)O(3) nanorods, and nanowires with and without
      nanoparticles on them have been successfully synthesized by a template-free
      hydrothermal route. The variation in hydrothermal temperature has not only
      affected the diameter of the nanostructure but also noticeably affected the
      morphology and optical properties of the alpha-Mn(2)O(3) nanostructure. The
      influence of temperature on the diameter, crystallinity, surface morphology and
      optical properties of the alpha-Mn(2)O(3) nanostructure have been characterized
      by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray
      analysis, transmission electron microscopy, high resolution transmission electron
      microscopy, Raman spectroscopy and UV-visible spectroscopy and photoluminescent
      (PL) spectroscopy. The results showed in our experimental conditions that single
      crystalline nanorods of the alpha-Mn(2)O(3) were obtained at a temperature of 180
      degrees C, while single crystalline nanowires were obtained by increasing the
      temperature to 240 and 300  degrees C. Nanowires with nanoparticles on them were
      obtained by increasing the temperature to 240  degrees C and nanowires without
      nanoparticles on them were obtained by increasing the temperature to 300  degrees
      C. The nanorods and nanowires obtained had a well-defined morphology. The
      nanowires synthesized at 300  degrees C exhibited an intense orange band PL
      spectrum.

PMID- 23011094
TI  - [From the work of the Commission for Hospital Hygiene and Infection Prevention].

PMID- 23011095
TI  - [Hygiene requirements for the reprocessing of medical devices. Recommendation of
      the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the
      Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical
      Devices (BfArM)].

PMID- 23011096
TI  - [Hygiene measures for infection or colonization with multidrug-resistant gram
      negative bacilli. Commission recommendation for hospital hygiene and infection
      prevention (KRINKO) at the Robert Koch Institute (RKI)].

PMID- 23011097
TI  - Home geriatric physiological measurements.
AB  - In an ageing society, the elderly can be monitored with numerous physiological,
      physical and passive devices. Sensors can be installed in the home for continuous
      mobility assistance and unobtrusive disease prevention. This review presents
      several modern sensors, which improve the quality of life and assist the elderly,
      disabled people and their caregivers. The main concept of geriatric sensors is
      that they are capable of providing assistance without limiting or disturbing the
      subject's daily routine, giving him or her greater comfort, pleasure and well
      being. Furthermore, this review includes associated technologies of
      wearable/implantable monitoring systems and the 'smart-house' project. This
      review concludes by discussing future challenges of the future aged society.

PMID- 23011098
TI  - Sevoflurane combined with ATP activates caspase-1 and triggers caspase-1
      dependent pyroptosis in murine J774 macrophages.
AB  - Sevoflurane is one of the most commonly used volatile anesthetics. Recent studies
      have shown that sevoflurane plays an important role in modulation of inflammation
      and immunity. However, little is known about the related molecular mechanisms.
      This study was designed to investigate the effects and mechanisms of sevoflurane
      on inflammatory cell death pyroptosis in the murine macrophage cell line J774
      cells. Sevoflurane combined with ATP could increase the level of activated
      caspase-1, pyroptosis, and reactive oxygen species (ROS). Furthermore, treatment
      of cells with the caspase-1 inhibitor Ac-YVAD-CMK dramatically decreased the
      percentage of pyroptosis. In addition, inhibition of ROS with N-acetyl-L-cysteine
      or diphenyleneiodonium significantly reduced the activated levels of caspase-1.
      These results demonstrated that sevoflurane combined with ATP could activate
      caspase-1 and trigger caspase-1-dependent pyroptosis through the modulation of
      ROS production.

PMID- 23011099
TI  - A phase II study of lapatinib for brain metastases in patients with HER2
      overexpressing breast cancer following trastuzumab based systemic therapy and
      cranial radiotherapy: subset analysis of Japanese patients.
AB  - BACKGROUND: It is known that one third of patients with human epidermal growth
      factor receptor 2 (HER2)-overexpressing metastatic breast cancer (MBC) treated
      with trastuzumab will develop brain metastases. As the development of brain
      metastases is fatal, controlling its progression is clinically meaningful.
      However, effective therapy for MBC patients with brain metastasis after cranial
      radiation is limited. The international clinical study in which six Japanese
      patients participated indicated the antitumor activity of lapatinib against brain
      metastases of HER2-overexpressing breast cancer. METHODS: The efficacy, safety,
      and pharmacokinetics of lapatinib 750 mg given twice daily to Japanese HER2
      overexpressing MBC patients with brain metastases were assessed as part of the
      international clinical study. RESULTS: Of six Japanese patients treated in this
      study, two patients had shown volumetric reduction >20 % in their central nervous
      system (CNS), one of whom had >50 % reduction. Three patients, including two of
      these patients, had shown >20 % volumetric reduction in non-CNS lesions.
      Frequently reported adverse events were diarrhea and rash, all of which were
      controllable. The AUC0-12 of lapatinib on day 28 was 1.74 times higher than that
      on day 1. CONCLUSION: These results suggest that lapatinib monotherapy 750 mg
      given twice daily can exert some efficacy and has potential as a clinically
      meaningful treatment option for Japanese HER2-overexpressing breast cancer
      patients with brain metastases after cranial radiation.

PMID- 23011100
TI  - Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by
      immediate cystectomy in patients with muscle-invasive bladder cancer, including
      those unfit for cisplatin: a prospective single-arm study.
AB  - BACKGROUND: Neoadjuvant cisplatin-based chemotherapy for patients with muscle
      invasive bladder cancer (BC) has better survival benefit than radical cystectomy
      (RC) alone. However, optimal dosing schedule, including drug selection, number of
      cycles, and interval between chemotherapy and cystectomy, as well as acceptable
      regimens remain to be established. We conducted a single-arm prospective study to
      evaluate efficacy and safety of neoadjuvant gemcitabine plus carboplatin (GCarbo)
      chemotherapy followed by immediate RC in patients with muscle-invasive BC,
      including cisplatin-unfit patients. METHODS: Between March 2005 and June 2011, we
      enrolled 116 patients with histologically proven muscle-invasive BC, including 44
      % of the patients who were identified as cisplatin-unfit. All participants
      received two courses of GCarbo therapy, gemcitabine 800 mg/m(2) administered on
      days 1, 8, and 15 and carboplatin with an area under the curve of four (AUC 4)
      administered on day 2. RC and bilateral pelvic lymphadenectomy were performed
      approximately within a month after cessation of chemotherapy. The primary
      endpoint was pT0 in the cystectomy specimen. Secondary endpoints were overall
      response rate, overall (OS) and disease-free survival (DFS), and toxicity.
      Survival after cystectomy was analyzed using the Kaplan-Meier method. RESULTS:
      The RC specimens of 28 (24.1 %) patients showed pT0. At a median follow-up period
      of 41 months, the OS and DFS rates were 89.7 and 86.3 %, respectively. No
      patients had grade 3/4 gastrointestinal toxicity or renal impairment.
      CONCLUSIONS: Neoadjuvant GCarbo therapy followed by immediate RC is safe, even in
      cisplatin-unfit patients, and provides a favorable pathological cancer-free
      state. The single-arm single-institution study design and relatively short
      observation period were limitations of this study.

PMID- 23011102
TI  - Pattern of prophylaxis administration for chemotherapy-induced nausea and
      vomiting: an analysis of city-based health insurance data.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) substantially affects
      patient quality of life. Although several guidelines have recommended the use of
      5-hydroxytryptamine 3 (5HT3) receptor antagonists with glucocorticoids to
      alleviate acute CINV, studies in other countries have reported that these
      recommendations were often not followed. We aimed to assess antiemetic use in
      community practices just before the Japanese Guidelines for the Appropriate Use
      of Antiemetics were published. METHODS: Using the insurance claims submitted to a
      public insurance program that covers residents up to 75 years old operated by a
      city with a population of 250,000, we examined the concurrent use of 5HT3
      receptor antagonists and glucocorticoids with high or moderate emetic risk
      chemotherapy. RESULTS: Overall, 448 patients received high or moderate emetic
      risk chemotherapy 1,342 times during the study period. The recommended antiemetic
      therapy was provided in 61.9 % (95 % confidence interval 55.5-68.3 %) of the
      treated patients, but the moderate emetic risk chemotherapy group received the
      recommended antiemetic therapy less frequently than the high emetic risk
      chemotherapy group (55.5 vs. 82.1 %, P < 0.01). A multivariate analysis showed
      that the use of non-recommended antiemetics and high emetic risk chemotherapy
      were associated with the recommended antiemetic therapy. Breast and lung cancer
      patients receiving high emetic risk chemotherapy received the recommended
      antiemetics in 100 % of cases, while only 67 % of patients with other cancer
      types received the recommended antiemetics. CONCLUSION: Despite several
      limitations associated with analysis of insurance claims, our study indicates
      that substantial room for improvement exists in the practice of preventing CINV.

PMID- 23011101
TI  - Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine
      followed by weekly paclitaxel in advanced non-small cell lung cancer.
AB  - BACKGROUND: Improving survival in non-small cell lung cancer (NSCLC) will require
      new strategies or new drugs. Sequential administration of conventional non-cross
      resistant cytotoxic drugs offers an opportunity to increase drug diversity while
      maintaining dose intensity. This Phase II trial was designed to assess the
      efficacy and feasibility of such a regimen in advanced NSCLC. METHODS: Patients
      with NSCLC stage IIIB or IV received as first-line treatment four cycles of
      carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m(2) (days 1 and 8) every 3
      weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80
      mg/m(2). RESULTS: In total, 46 patients were included. Median age was 59.6 years
      (range 41.3-74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology
      Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3
      %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of
      carboplatin-gemcitabine and 35 patients received at least 1 cycle of paclitaxel,
      of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The
      overall objective response rate was 49 %. Sixteen (37 %) patients had a response
      to carboplatin-gemcitabine, increasing to 21 (49 %) patients after administration
      of paclitaxel. Of the 13 assessable patients who showed a partial response (PR)
      on carboplatin-gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of
      19 assessable patients with stable disease (SD) on carboplatin-gemcitabine, 4 (21
      %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped
      because of toxicity. CONCLUSION: Sequential chemotherapy with carboplatin
      gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC
      patients.

PMID- 23011103
TI  - A retrospective analysis of periodontitis during bevacizumab treatment in
      metastatic colorectal cancer patients.
AB  - BACKGROUND: Bevacizumab, a humanized anti-vascular endothelial growth factor
      monoclonal antibody, has showed clinical benefits in patients with metastatic
      colorectal cancer. Periodontitis has been observed infrequently in bevacizumab
      containing chemotherapy in clinical practice. The purpose of this study was to
      retrospectively investigate bevacizumab-related periodontitis in metastatic
      colorectal cancer patients. METHODS: From January 2008 to March 2010, 274
      patients received bevacizumab-containing chemotherapy at the National Cancer
      Center Hospital in Tokyo. Patients who had consulted the dentist for
      periodontitis were included in the study. We examined the interval between the
      initiation of the first bevacizumab administration and the day of the
      consultation with the dentist. Periodontitis was evaluated before and after
      conservative therapy. RESULTS: Twenty-six patients (9.5 % of the 274 metastatic
      colorectal cancer patients) were included in this study. The median age was 60
      years (range 30-79 years). Nineteen (73 %) patients had a good performance status
      of 0. The combination regimens used with bevacizumab were infusional 5
      fluorouracil, leucovorin, and oxaliplatin (FOLFOX, 53 %); infusional 5
      fluorouracil, leucovorin, and irinotecan (FOLFIRI, 27 %); capecitabine +
      oxaliplatin (CapeOX, 8 %); S-1 + oxaliplatin (8 %); and S-1 + irinotecan (4 %).
      The median time from bevacizumab administration to the consultation with a
      dentist for periodontitis was 69 days (range 12-390 days), and the median number
      of bevacizumab administrations was 3.5 (range 1-25). After conservative therapy,
      22 (85 %) patients with periodontitis showed an improvement. CONCLUSIONS:
      Periodontitis occurred frequently in patients receiving bevacizumab. The
      conservative therapy for periodontitis was very effective, and the prophylaxitic
      treatment was important.

PMID- 23011105
TI  - Do plants use airborne cues to recognize herbivores on their neighbours?
AB  - Plants show defensive responses after exposure to volatiles from neighbouring
      plants infested by herbivores. When a plant's neighbours host only species of
      herbivores that do not feed on the plant itself, the plant can conserve energy by
      maintaining a low defence level. An intriguing question is whether plants respond
      differently to volatiles from plants infested by herbivores that pose greater or
      lesser degrees of danger. We examined the secretion of extrafloral nectar (EFN)
      in lima bean plants exposed to volatiles from cabbage plants infested by common
      cutworm, two-spotted spider mites, or diamondback moth larvae. Although the first
      two herbivore species feed on lima bean plants, diamondback moth larvae do not.
      As a control, lima bean plants were exposed to volatiles from uninfested cabbage
      plants. Only when exposed to volatiles from cabbage plants infested by spider
      mites did lima bean plants significantly increase their EFN secretion compared
      with the control. Increased EFN secretion can function as an indirect defence by
      supplying the natural enemies of herbivores with an alternative food source. Of
      the three herbivore species, spider mites were the most likely to move from
      cabbage plants to lima bean plants and presumably posed the greatest threat.
      Although chemical analyses showed differences among treatments in volatiles
      produced by herbivore-infested cabbage plants, which compounds or blends
      triggered the increased secretion of EFN by lima bean plants remains unclear.
      Thus, our results show that plants may tune their defence levels according to
      herbivore risk level.

PMID- 23011106
TI  - Community structures of Mesostigmata, Prostigmata and Oribatida in broad-leaved
      regeneration forests and conifer plantations of various ages.
AB  - The community structures of Mesostigmata, Prostigmata, and Oribatida in the soil
      of broad-leaved regeneration forests and conifer plantations of various ages were
      assessed alongside soil and plant environmental variables using three response
      metrics (density, species richness, and species-abundance distribution). The
      density and species richness of mites recovered swiftly after clear-cutting or
      replanting. Oribatid mites dominated the soil mite communities in terms of
      densities and species richness for both forest types. Soil mite communities in
      broad-leaved forests was related to forest age, the crown tree communities index,
      and forest-floor litter weight. In contrast, soil mite communities in the conifer
      plantation sites were related to various indices of understory plants. The
      development of the understory plants was synchronized with the silvicultural
      schedules, including a closed canopy and thinning. Such a conifer plantation
      management may affect indirectly the community of mites.

PMID- 23011108
TI  - Geotaxis and leaf-surface preferences mitigate negative effects of a predatory
      mite on an herbivorous mite.
AB  - Reproductive success and population growth of an herbivorous mite are limited by
      activities of phytoseiid predators. However, occurrences on upper versus lower
      leaf surfaces are sometimes mismatched between these prey and predators. The
      mismatch potentially mitigates predation risk for the prey species. We assessed
      factors that affect mite distributions on leaf surfaces, testing whether the
      presence of the phytoseiid mite Phytoseius nipponicus alters the leaf-surface
      distribution and reproductive success of the herbivorous false spider mite
      Brevipalpus obovatus. The host plant was Viburnum erosum var. punctatum
      (Adoxaceae). Leaves were set in natural (TRUE) and reversed (upside down;
      INVERTED) orientations using experimental devices. Both surfaces were accessible
      to mites. We detected lower and abaxial leaf-surface preferences in P.
      nipponicus. In contrast, upper and adaxial surfaces were preferred by B.
      obovatus. Thus, prey and predatory mites accumulated on different sides of
      leaves. Presence of the predator also indirectly decreased egg production in B.
      obovatus. Brevipalpus obovatus females actively avoided leaf surfaces with
      elevated predator numbers; these females shifted their distributions and changed
      oviposition sites to leaf surfaces with fewer predators. In consequence, B.
      obovatus eggs on the upper sides of leaves were less frequently preyed upon than
      were those on lower sides. We suggest that upper leaf-surface exploitation in
      this particular herbivorous mite species mitigates predation risk from phytoseiid
      mites, which prefer lower leaf surfaces.

PMID- 23011107
TI  - Comparison of thermal activity thresholds of the spider mite predators
      Phytoseiulus macropilis and Phytoseiulus persimilis (Acari: Phytoseiidae).
AB  - The lower and upper thermal activity thresholds of the predatory mite
      Phytoseiulus macropilis Banks (Acari: Phytoseiidae) were compared with those of
      its prey Tetranychus urticae Koch (Acari: Tetranychidae) and one of the
      alternative commercially available control agents for T. urticae, Phytoseiulus
      persimilis Athias-Henriot. Adult female P. macropilis retained ambulatory
      function (CTmin) and movement of appendages (chill coma) at significantly lower
      temperatures (8.2 and 0.4  degrees C, respectively) than that of P. persimilis
      (11.1 and 3.3  degrees C) and T. urticae (10.6 and 10.3  degrees C). As the
      temperature was raised, P. macropilis ceased walking (CTmax) and entered heat
      coma (42.7 and 43.6  degrees C), beyond the upper locomotory limits of P.
      persimilis (40.0 and 41.1  degrees C), but before T. urticae (47.3 and 48.7 
      degrees C). Walking speeds were investigated and P. persimilis was found to have
      significantly faster ambulation than P. macropilis and T. urticae across a range
      of temperatures. The lower thermal activity threshold data indicate that P.
      macropilis will make an effective biological control agent in temperate climates.

PMID- 23011109
TI  - Organization of functional postural responses following perturbations in multiple
      directions in elderly fallers standing quietly.
AB  - The objective of the study was to assess functional postural responses by
      analyzing the center-of-pressure trajectories resulting from perturbations
      delivered in multiple directions to elderly fallers. Ten elderly individuals were
      standing quietly on two force platforms while an apparatus delivered controlled
      perturbations at the level of pelvis in eight directions: 'forward (FW)' and
      'backward (BW)' [anterioposterior plane (AP)], 'left (LT)' and 'right (RT)'
      [mediolateral plane (ML)] and four combinations of these principal directions:
      forward-left (FL), forward-right (FR), backward-left (BL) and backward-right
      (BR). Perturbations were repeated randomly four times in each direction. Peak
      amplitude responses (PAR AP and PAR ML) and times to reach peak amplitude
      responses (TPAR-AP and TPAR-ML) were extracted for each perturbation direction
      from acquired center-of-pressure data. One-way analysis of variance was used to
      test differences between directionally-similar perturbation directions. Balance
      abilities were assessed by means of Berg Balance Scale. Average Berg Balance
      Scale for the group resulted in 33.9+/-5.8 points, which means that the
      participants were at greater risk of fall. The comparison of the group averaged
      PARAP and TPAR-AP in all 'forward' directions (FW, FL, FR) as well in all
      'backward' directions (BW, BL, BR) have not shown statistically significant
      differences. The comparison of the group averaged PARML and TPAR-ML in all 'left'
      directions (LT, FL, BL) as well in all 'right' directions (RT, FR, BR) have not
      shown statistically significant differences. These results suggest that a
      principle of decoupled control may to a large extent be preserved also in elderly
      with clearly diminished balancing abilities, which implies that the accuracy in
      the assessment of perturbation direction may be well preserved also in very old
      age.

PMID- 23011110
TI  - Nanoscaled tin dioxide films processed from organotin-based hybrid materials: an
      organometallic route toward metal oxide gas sensors.
AB  - Nanocrystalline tin dioxide (SnO(2)) ultra-thin films were obtained employing a
      straightforward solution-based route that involves the calcination of bridged
      polystannoxane films processed by the sol-gel process from bis(triprop-1
      ynylstannyl)alkylene and -arylene precursors. These films have been thoroughly
      characterized by FTIR, contact angle measurements, X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), atomic force (AFM) and scanning electron (SEM)
      microscopies. Annealing at a high temperature gave 30-35 nm thick cassiterite
      SnO(2) films with a mean crystallite size ranging from 4 to 7 nm depending on the
      nature of the organic linker in the distannylated compound used as a precursor.
      In the presence of H(2) and CO gases, these layers led to highly sensitive,
      reversible and reproducible responses. The sensing properties were discussed in
      regard to the crystallinity and porosity of the sensing body that can be tuned by
      the nature of the precursor employed. Organometallic chemistry combined with the
      sol-gel process therefore offers new possibilities toward metal oxide
      nanostructures for the reproducible and sensitive detection of combustible and
      toxic gases.

PMID- 23011111
TI  - Ultrastructural studies on the sporogenous tissue and anther wall of Leucojum
      aestivum (amaryllidaceae) in different developmental stages.
AB  - In this study, ultrastructures of anther wall and sporogenous tissue of Leucojum
      aestivum were investigated during different developmental stages. Cytomictic
      channels were seen between pollen mother cells during prophase I. Polar
      distribution was described in the organelle content of pollen mother cells and
      microspores in early phases of microsporogenesis and also in pollen mitosis.
      Active secretion was observed in tapetal cells. Previous reports about
      developmental stages of male gametophyte were compared with the results of this
      study.

PMID- 23011112
TI  - Cholinesterase as inflammatory markers in a experimental infection by Trypanosoma
      evansi in rabbits.
AB  - The aim of this study is to evaluate the role of cholinesterases as an
      inflammatory marker in acute and chronic infection by Trypanosoma evansi in
      rabbits experimentally infected. Twelve adult female New Zealand rabbits were
      used and divided into two groups with 6 animals each: control group (rabbits 1-6)
      and infected group (rabbits 7-12). Infected group received intraperitoneally 0.5
      mL of blood from a rat containing 108 parasites per animal. Blood samples used
      for cholinesterases evaluation were collected on days 0, 2, 7, 12, 27, 42, 57,
      87, 102 and 118 days post-inoculation (PI). Increased activity (P<0.05) of
      butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were observed in the
      blood on days 7 and 27, respectively and no differences were observed in
      cholinesterase activity in other periods. No significant difference in AChE
      activity (P>0.05) was observed in the encephalic structures. The increased
      activities of AChE and BChE probably have a pro-inflammatory purpose, attempting
      to reduce the concentration of acetylcholine, a neurotransmitter which has an
      anti-inflammatory property. Therefore, cholinesterase may be inflammatory markers
      in infection with T. evansi in rabbits.

PMID- 23011113
TI  - Ameliorative potential of Butea monosperma on chronic constriction injury of
      sciatic nerve induced neuropathic pain in rats.
AB  - The present study was designed to investigate the ameliorative role of ethanolic
      extract from leaves of Butea monosperma in chronic constriction injury (CCI) of
      sciatic nerve induced neuropathic pain in rats. Hot plate, acetone drop, paw
      pressure, Von Frey hair and tail immersion tests were performed to assess the
      degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia
      & allodynia in the left hind paw and tail thermal hyperalgesia. Further on,
      thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and
      total calcium levels were estimated to assess the biochemical changes in the
      sciatic nerve tissue. Histopathological changes were also observed in the sciatic
      nerve tissue. Ethanolic extract of Butea monosperma leaves and pregabalin
      (serving as positive control) were administered for 14 consecutive days starting
      from the day of surgery. CCI resulted in significant changes in behavioural and
      biochemical parameters. Pretreatment of Butea monosperma attenuated CCI induced
      development of behavioural, biochemical and histopathological alterations in a
      dose dependent manner, which is comparable to that of pregabalin pretreated
      group. These findings may be attributed to its potential anti-oxidative,
      neuroprotective and calcium channel modulatory actions of Butea monosperma.

PMID- 23011114
TI  - Synthesis and optical properties of macrocyclic lanthanide(III) chelates as new
      reagents for luminescent biolabeling.
AB  - The convenient and efficient synthesis of two macrocyclic ligands (15- and 18
      membered) based on a dipyrido-6,7,8,9-tetrahydrophenazine (dpqc) or 2,2':6',2''
      terpyridine (tpy) heterocycle and a DTTA (diethylenetriaminetriacetic acid)
      skeleton is described. In these ligands the DTTA skeleton contains an additional
      extracyclic functionality (NH(2) group) suitable for covalent attachment to
      bioactive molecules. These octa- and nonadentate ligands form very stable and
      luminescent neutral lanthanide complexes in aqueous solutions at physiological
      pH. The corresponding Eu(III) and Tb(III) complexes are characterized by a
      maximum absorption wavelength compatible with nitrogen laser excitation (337 nm)
      and attractive lifetimes and quantum yields. Further introduction of a maleimide
      bioconjugatable handle in the Eu(III) complexes was investigated and a valuable
      luminescence brightness above 1500 dm(3) mol(-1) cm(-1) at 337 nm was obtained
      with the corresponding Eu(III) tpy-derivative. Finally, these two luminescent
      chelates were grafted onto thiol residues of a model antibody (Mab GSS11) without
      loss of their luminescent properties.

PMID- 23011116
TI  - Congenital lung abnormalities: a pictorial review of imaging findings.
AB  - Congenital lung malformations (CLM) comprise a broad spectrum of maldevelopment
      that spans a continuum of maldevelopment involving parenchyma, bronchi, and
      vasculature. They may present as respiratory symptoms at birth and can be the
      source of morbidity and mortality. Early diagnosis is important for adequate
      therapy to prevent complications, such as recurrent infections, or to help normal
      lung development. Prenatal diagnosis of CLM using ultrasound (US) and magnetic
      resonance imaging (MRI) has increased, but chest radiography and computed
      tomography (CT) still play important roles in making diagnosis. This article
      reviews the clinical and radiographic features of various CLM.

PMID- 23011115
TI  - In Zucker diabetic fatty rats, subclinical diabetic neuropathy increases in vivo
      lidocaine block duration but not in vitro neurotoxicity.
AB  - BACKGROUND AND OBJECTIVES: Application of local anesthetics may lead to nerve
      damage. Increasing evidence suggests that risk of neurotoxicity is higher in
      patients with diabetic peripheral neuropathy. In addition, block duration may be
      prolonged in neuropathy. We sought to investigate neurotoxicity in vitro and
      block duration in vivo in a genetic animal model of diabetes mellitus type 2.
      METHODS: In the first experiments, neurons harvested from control Zucker diabetic
      fatty (ZDF) rats were exposed to acute (24 hours) or chronic (72 hours)
      hyperglycemia, followed by incubation with lidocaine 40 mM (approximately 1%). In
      a second experiment, neurons harvested from control ZDF rats, or diabetic ZDF
      rats, were incubated with lidocaine, with or without SB203580, an inhibitor of
      the p38 mitogen-activated protein kinase. Finally, we performed sciatic nerve
      block (lidocaine 2%, 0.2 mL) in control or diabetic ZDF rats and measured motor
      and nociceptive block duration. RESULTS: In vitro, neither acute nor chronic
      hyperglycemia altered neurotoxic properties of lidocaine. In vitro, incubation of
      neurons with lidocaine resulted in a slightly decreased survival ratio when
      neurons were harvested from diabetic (57% +/- 19%) as compared with control (64%
      +/- 9%) rats. The addition of SB203580 partly reversed this enhanced neurotoxic
      effect and raised survival to 71% +/- 12% in diabetic neurons and 66% +/- 9% in
      control rats, respectively. In vivo, even though no difference was detected at
      baseline testing, motor block was significantly prolonged in diabetic as compared
      with control rats (137 +/- 16 vs 86 +/- 17 min). CONCLUSIONS: In vitro, local
      anesthetic neurotoxicity was more pronounced on neurons from diabetic animals,
      but the survival difference was small. In vivo, subclinical neuropathy leads to
      substantial prolongation of block duration. We conclude that early diabetic
      neuropathy increases block duration, whereas the observed increase in toxicity
      was small.

PMID- 23011117
TI  - A low-cost sensitizer based on a phenolic resin for charge-transfer type
      photocatalysts working under visible light.
AB  - Phenolic resin (denoted as PR) was used as an economical sensitizer of titania to
      achieve efficient visible light photocatalytic activity. Through the surface
      complexation of PR with TiO(2), we demonstrate that the complexed PR layer
      sensitizes TiO(2) under visible light through the ligand-to-metal charge transfer
      (LMCT) mechanism.

PMID- 23011118
TI  - Benzodiazepine misadventure in acute alcohol withdrawal: the transition from
      delirium tremens to ICU delirium.

PMID- 23011119
TI  - Spinal cord stimulation for a woman with complex regional pain syndrome who
      wished to get pregnant.
AB  - A woman with complex regional pain syndrome (CRPS) in the right lower extremity
      who wished to discontinue medications to get pregnant underwent implantation of a
      spinal cord stimulation system (SCS). An electrode lead was placed at Th(10-11)
      in the epidural space, accessed via the L(2-3) interspace with a paramedian
      approach, and a pulse generator was implanted in the left buttock. She kept the
      SCS on 24 h a day. After she had experienced several chemical abortions, finally
      she got pregnant via artificial insemination. She had an uneventful delivery of a
      healthy baby by cesarean resection under spinal anesthesia. In a patient with
      CRPS who has an implanted SCS system and wishes to get pregnant, the electrode
      lead into the low thoracic epidural space should be accessed via the high lumbar
      intervertebral space in consideration of a future requirement for spinal or
      epidural anesthesia for cesarean section. The generator should be placed in the
      buttock to prevent impairment of the SCS system being caused by the enlarged
      abdomen during pregnancy. Although we were apprehensive of adverse effects owing
      to the electromagnetic field force and change of blood flow in the pelvic
      viscera, our patient had a successful delivery. SCS is a favorable option for
      patients with CRPS who wish to get pregnant.

PMID- 23011120
TI  - Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic
      resonance imaging.
AB  - SF188/V+ is a highly vascular human glioma model that is based on transfection of
      vascular endothelial growth factor (VEGF) cDNA into SF188/V- cells. This study
      aims to assess its growth and vascularity properties in vivo in a rat model.
      Thirty-two adult rats were inoculated with SF188/V+ tumor cells, and, for
      comparison, five were inoculated with SF188/V- tumor cells. Several conventional
      magnetic resonance imaging (MRI) sequences were acquired, and several
      quantitative structural (T(2) and T(1)), functional [isotropic apparent diffusion
      coefficient (ADC) and blood flow], and molecular [protein and peptide-based amide
      proton transfer (APT)] MRI parameters were mapped on a 4.7 T animal scanner. In
      rats inoculated with SF188/V+ tumor cells, conventional T(2)-weighted images
      showed a highly heterogeneous tumor mass, and post-contrast T(1)-weighted images
      showed a heterogeneous, strong enhancement of the mass. There were moderate
      increases in T(2), T(1), and ADC, and large increases in blood flow and APT in
      the tumor, compared to contralateral brain tissue. Microscopic examination
      revealed prominent vascularity and hemorrhage in the VEGF-secreting xenografts as
      compared to controls, and immunohistochemical staining confirmed increased
      expression of VEGF in tumor xenografts. Our results indicate that the SF188/V+
      glioma model exhibits some MRI and histopathology features that closely resemble
      human glioblastoma.

PMID- 23011121
TI  - Spark erosion: a high production rate method for producing Bi(0.5)Sb(1.5)Te3
      nanoparticles with enhanced thermoelectric performance.
AB  - We report a new 'spark erosion' technique for producing high-quality 
      thermoelectric nanoparticles at a remarkably high rate and with enhanced
      thermoelectric properties. The technique was utilized to synthesize p-type
      Bi(0.5)Sb(1.5)Te(3) nanoparticles with a production rate as high as 135 g h(-1),
      using a relatively small laboratory apparatus and low energy consumption. The
      compacted nanocomposite samples made from these nanoparticles exhibit a well
      defined, 20-50 nm size nanograin microstructure, and show an enhanced figure of
      merit, ZT, of 1.36 at 360 K. Such a technique is essential for providing
      inexpensive, oxidation-free nanoparticles which are required for the fabrication
      of high performance thermoelectric devices for power generation from waste heat,
      and for refrigeration.

PMID- 23011122
TI  - Oxygen consumption, oxygen cost, heart rate, and perceived effort during split
      belt treadmill walking in young healthy adults.
AB  - During split-belt treadmill walking the speed of the treadmill under one limb is
      faster than the belt under the contralateral limb. This unique intervention has
      shown evidence of acutely improving gait impairments in individuals with
      neurologic impairment such as stroke and Parkinson's disease. However, oxygen
      use, heart rate and perceived effort associated with split-belt treadmill walking
      are unknown and may limit the utility of this locomotor intervention. To better
      understand the intensity of this new intervention, this study was undertaken to
      examine the oxygen consumption, oxygen cost, heart rate, and rating of perceived
      exertion associated with split-belt treadmill walking in young healthy adults.
      Fifteen participants completed three sessions of treadmill walking: slow speed
      with belts tied, fast speed with belts tied, and split-belt walking with one leg
      walking at the fast speed and one leg walking at the slow speed. Oxygen
      consumption, heart rate, and rating of perceived exertion were collected during
      each walking condition and oxygen cost was calculated. Results revealed that
      oxygen consumption, heart rate, and perceived effort associated with split-belt
      walking were higher than slow treadmill walking, but only oxygen consumption was
      significantly lower during both split-belt walking than fast treadmill walking.
      Oxygen cost associated with slow treadmill walking was significantly higher than
      fast treadmill walking. These findings have implications for using split-belt
      treadmill walking as a rehabilitation tool as the cost associated with split-belt
      treadmill walking may not be higher or potentially more detrimental than that
      associated with previously used treadmill training rehabilitation strategies.

PMID- 23011123
TI  - Influence of muscle strength to weight ratio on functional task performance.
AB  - Existing models of muscle deconditioning such as bed rest are expensive and time
      consuming. We propose a new model utilizing a weighted suit to manipulate muscle
      strength, power, or endurance relative to body weight. The aims of the study were
      to determine as to which muscle measures best predict functional task performance
      and to determine muscle performance thresholds below which task performance is
      impaired. Twenty subjects performed seven occupational astronaut tasks (supine
      and upright seat egress and walk, rise from fall, hatch opening, ladder climb,
      object carry, and construction board activity), while wearing a suit weighted
      with 0-120 % of body weight. Models of the relationship between muscle
      function/body weight and task completion time were developed using fractional
      polynomial regression and verified with pre- and post-flight astronaut
      performance data. Spline regression was used to identify muscle function
      thresholds for each task. Upright seat egress and walk was the most difficult
      task according to the spline regression analysis thresholds. Thresholds
      normalized to body weight were 17.8 N/kg for leg press isometric force, 17.6 W/kg
      for leg press power, 78.8 J/kg for leg press work, 5.9 N/kg isometric knee
      extension and 1.9 Nm/kg isokinetic knee extension torque. Leg press maximal
      isometric force/body weight was the most reliable measure for modeling
      performance of ambulatory tasks. Laboratory-based manipulation of relative
      strength has promise as an analog for spaceflight-induced loss of muscle
      function. Muscle performance values normalized to body weight can be used to
      predict occupational task performance and to establish relevant strength
      thresholds.

PMID- 23011124
TI  - Drug-drug interactions that should be non-interruptive in order to reduce alert
      fatigue in electronic health records.
AB  - OBJECTIVE: Alert fatigue represents a common problem associated with the use of
      clinical decision support systems in electronic health records (EHR). This
      problem is particularly profound with drug-drug interaction (DDI) alerts for
      which studies have reported override rates of approximately 90%. The objective of
      this study is to report consensus-based recommendations of an expert panel on DDI
      that can be safely made non-interruptive to the provider's workflow, in EHR, in
      an attempt to reduce alert fatigue. METHODS: We utilized an expert panel process
      to rate the interactions. Panelists had expertise in medicine, pharmacy,
      pharmacology and clinical informatics, and represented both academic institutions
      and vendors of medication knowledge bases and EHR. In addition, representatives
      from the US Food and Drug Administration and the American Society of Health
      System Pharmacy contributed to the discussions. RESULTS: Recommendations and
      considerations of the panel resulted in the creation of a list of 33 class-based
      low-priority DDI that do not warrant being interruptive alerts in EHR. In one
      institution, these accounted for 36% of the interactions displayed. DISCUSSION:
      Development and customization of the content of medication knowledge bases that
      drive DDI alerting represents a resource-intensive task. Creation of a
      standardized list of low-priority DDI may help reduce alert fatigue across EHR.
      CONCLUSIONS: Future efforts might include the development of a consortium to
      maintain this list over time. Such a list could also be used in conjunction with
      financial incentives tied to its adoption in EHR.

PMID- 23011125
TI  - Live imaging of DORNROSCHEN and DORNROSCHEN-LIKE promoter activity reveals
      dynamic changes in cell identity at the microcallus surface of Arabidopsis
      embryonic suspensions.
AB  - KEY MESSAGE : Transgenic DRN::erGFP and DRNL::erGFP reporters access the window
      from explanting Arabidopsis embryos to callus formation and provide evidence for
      the acquisition of shoot meristem cell fates at the microcalli surface. The
      DORNROSCHEN (DRN) and DORNROSCHEN-LIKE (DRNL) genes encode AP2-type transcription
      factors, which are activated shortly after fertilisation in the zygotic
      Arabidopsis embryo. We have monitored established transgenic DRN::erGFP and
      DRNL::erGFP reporter lines using live imaging, for expression in embryonic
      suspension cultures and our data show that transgenic fluorophore markers are
      suitable to resolve dynamic changes of cellular identity at the surface of
      microcalli and enable fluorescence-activated cell sorting. Although DRN::erGFP
      and DRNL::erGFP are both activated in surface cells, their promoter activity
      marks different cell identities based on real-time PCR experiments and whole
      transcriptome microarray data. These transcriptome analyses provide no evidence
      for the maintenance of embryogenic identity under callus-inducing high-auxin
      tissue culture conditions but are compatible with the acquisition of shoot
      meristem cell fates at the surface of suspension calli.

PMID- 23011127
TI  - Escherichia coli noncoding RNAs can affect gene expression and physiology of
      Caenorhabditis elegans.
AB  - Food and other environmental factors affect gene expression and behaviour of
      animals. Differences in bacterial food affect the behaviour and longevity of
      Caenorhabditis elegans. However, no research has been carried out to investigate
      whether bacteria could utilize endogenous RNAs to affect C. elegans physiology.
      Here we show that two Escherichia coli endogenous noncoding RNAs, OxyS and DsrA,
      impact on the physiology of C. elegans. OxyS downregulates che-2, leading to
      impairment in C. elegans chemosensory behaviour and DsrA suppresses
      diacylglycerol lipase gene F42G9.6, leading to a decrease in longevity. We also
      examine some genes in the C. elegans RNA interference pathway for their possible
      involvement in the effects of OxyS and DsrA. Other bacteria, such as Bacillus
      mycoides, may also utilize its noncoding RNAs to interfere with gene expression
      in C. elegans. Our results demonstrate that E. coli noncoding RNAs can regulate
      gene expression and physiological conditions of C. elegans and indicate that
      noncoding RNAs might have interspecies ecological roles.

PMID- 23011128
TI  - Insights into the biomedical effects of carboxylated single-wall carbon nanotubes
      on telomerase and telomeres.
AB  - Both human telomeric G-rich and C-rich DNA have been considered as specific drug
      targets for cancer therapy. However, due to i-motif structure instability and
      lack of specific binding agents, it remains unclear whether stabilization of
      telomeric i-motif can inhibit telomerase activity. Single-walled carbon nanotubes
      (SWNTs) have been reported as the first ligand that can selectively stabilize
      human telomeric i-motif DNA. Here we report that SWNTs can inhibit telomerase
      activity through stabilization of i-motif structure. The persistence of i-motif
      and the concomitant G-quadruplex eventually leads to telomere uncapping and
      displaces telomere-binding proteins from telomere. The dysfunctional telomere
      triggers DNA damage response and elicits upregulation of p16 and p21 proteins.
      This is the first example that SWNTs can inhibit telomerase activity and
      interfere with the telomere functions in cancer cells. These results provide new
      insights into understanding the biomedical effects of SWNTs and the biological
      importance of i-motif DNA.

PMID- 23011129
TI  - Integrable microwave filter based on a photonic crystal delay line.
AB  - The availability of a tunable delay line with a chip-size footprint is a crucial
      step towards the full implementation of integrated microwave photonic signal
      processors. Achieving a large and tunable group delay on a millimetre-sized chip
      is not trivial. Slow light concepts are an appropriate solution, if propagation
      losses are kept acceptable. Here we use a low-loss 1.5 mm-long photonic crystal
      waveguide to demonstrate both notch and band-pass microwave filters that can be
      tuned over the 0-50-GHz spectral band. The waveguide is capable of generating a
      controllable delay with limited signal attenuation (total insertion loss below 10
      dB when the delay is below 70 ps) and degradation. Owing to the very small
      footprint of the delay line, a fully integrated device is feasible, also
      featuring more complex and elaborate filter functions.

PMID- 23011130
TI  - Direct visualization of cell division using high-resolution imaging of M-phase of
      the cell cycle.
AB  - Current approaches to monitor and quantify cell division in live cells, and
      reliably distinguish between acytokinesis and endoreduplication, are limited and
      complicate determination of stem cell pool identities. Here we overcome these
      limitations by generating an in vivo reporter system using the scaffolding
      protein anillin fused to enhanced green fluorescent protein, to provide high
      spatiotemporal resolution of mitotic phase. This approach visualizes cytokinesis
      and midbody formation as hallmarks of expansion of stem and somatic cells, and
      enables distinction from cell cycle variations. High-resolution microscopy in
      embryonic heart and brain tissues of enhanced green fluorescent protein-anillin
      transgenic mice allows live monitoring of cell division and quantitation of cell
      cycle kinetics. Analysis of cell division in hearts post injury shows that border
      zone cardiomyocytes in the infarct respond with increasing ploidy, but not cell
      division. Thus, the enhanced green fluorescent protein-anillin system enables
      monitoring and measurement of cell division in vivo and markedly simplifies in
      vitro analysis in fixed cells.

PMID- 23011131
TI  - The nuclear hormone receptor PPARgamma counteracts vascular calcification by
      inhibiting Wnt5a signalling in vascular smooth muscle cells.
AB  - Vascular calcification is a hallmark of advanced atherosclerosis. Here we show
      that deletion of the nuclear receptor PPARgamma in vascular smooth muscle cells
      of low density lipoprotein receptor (LDLr)-deficient mice fed an atherogenic diet
      high in cholesterol, accelerates vascular calcification with chondrogenic
      metaplasia within the lesions. Vascular calcification in the absence of PPARgamma
      requires expression of the transmembrane receptor LDLr-related protein-1 in
      vascular smooth muscle cells. LDLr-related protein-1 promotes a previously
      unknown Wnt5a-dependent prochondrogenic pathway. We show that PPARgamma protects
      against vascular calcification by inducing the expression of secreted frizzled
      related protein-2, which functions as a Wnt5a antagonist. Targeting this
      signalling pathway may have clinical implications in the context of common
      complications of atherosclerosis, including coronary artery calcification and
      valvular sclerosis.

PMID- 23011132
TI  - The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte
      autophagy.
AB  - Pathological growth of cardiomyocytes (hypertrophy) is a major determinant for
      the development of heart failure, one of the leading medical causes of mortality
      worldwide. Here we show that the microRNA (miRNA)-212/132 family regulates
      cardiac hypertrophy and autophagy in cardiomyocytes. Hypertrophic stimuli
      upregulate cardiomyocyte expression of miR-212 and miR-132, which are both
      necessary and sufficient to drive the hypertrophic growth of cardiomyocytes. MiR
      212/132 null mice are protected from pressure-overload-induced heart failure,
      whereas cardiomyocyte-specific overexpression of the miR-212/132 family leads to
      pathological cardiac hypertrophy, heart failure and death in mice. Both miR-212
      and miR-132 directly target the anti-hypertrophic and pro-autophagic FoxO3
      transcription factor and overexpression of these miRNAs leads to hyperactivation
      of pro-hypertrophic calcineurin/NFAT signalling and an impaired autophagic
      response upon starvation. Pharmacological inhibition of miR-132 by antagomir
      injection rescues cardiac hypertrophy and heart failure in mice, offering a
      possible therapeutic approach for cardiac failure.

PMID- 23011133
TI  - Genetic architecture supports mosaic brain evolution and independent brain-body
      size regulation.
AB  - The mammalian brain consists of distinct parts that fulfil different functions.
      Finlay and Darlington have argued that evolution of the mammalian brain is
      constrained by developmental programs, suggesting that different brain parts are
      not free to respond individually to selection and evolve independent of other
      parts or overall brain size. However, comparisons among mammals with matched
      brain weights often reveal greater differences in brain part size, arguing
      against strong developmental constraints. Here we test these hypotheses using a
      quantitative genetic approach involving over 10,000 mice. We identify independent
      loci for size variation in seven key parts of the brain, and observe that brain
      parts show low or no phenotypic correlation, as is predicted by a mosaic
      scenario. We also demonstrate that variation in brain size is independently
      regulated from body size. The allometric relations seen at higher phylogenetic
      levels are thus unlikely to be the product of strong developmental constraints.

PMID- 23011134
TI  - Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile
      X syndrome.
AB  - Fragile X syndrome, the most commonly known genetic cause of autism, is due to
      loss of the fragile X mental retardation protein, which regulates signal
      transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental
      retardation protein deletion in mice enhances metabotropic glutamate receptor-5
      dependent long-term depression in the hippocampus and cerebellum. Here we show
      that a distinct type of metabotropic glutamate receptor-5-dependent long-term
      depression at excitatory synapses of the ventral striatum and prefrontal cortex,
      which is mediated by the endocannabinoid 2-arachidonoyl-sn-glycerol, is absent in
      fragile X mental retardation protein-null mice. In these mutants, the
      macromolecular complex that links metabotropic glutamate receptor-5 to the 2
      arachidonoyl-sn-glycerol-producing enzyme, diacylglycerol lipase-alpha
      (endocannabinoid signalosome), is disrupted and metabotropic glutamate receptor-5
      dependent 2-arachidonoyl-sn-glycerol formation is compromised. These changes are
      accompanied by impaired endocannabinoid-dependent long-term depression.
      Pharmacological enhancement of 2-arachidonoyl-sn-glycerol signalling normalizes
      this synaptic defect and corrects behavioural abnormalities in fragile X mental
      retardation protein-deficient mice. The results identify the endocannabinoid
      signalosome as a molecular substrate for fragile X syndrome, which might be
      targeted by therapy.

PMID- 23011135
TI  - Thyroid hormone determines the start of the sensitive period of imprinting and
      primes later learning.
AB  - Filial imprinting in precocial birds is the process of forming a social
      attachment during a sensitive or critical period, restricted to the first few
      days after hatching. Imprinting is considered to be part of early learning to aid
      the survival of juveniles by securing maternal care. Here we show that the
      thyroid hormone 3,5,3'-triiodothyronine (T(3)) determines the start of the
      sensitive period. Imprinting training in chicks causes rapid inflow of T(3),
      converted from circulating plasma thyroxine by Dio2, type 2 iodothyronine
      deiodinase, in brain vascular endothelial cells. The T(3) thus initiates and
      extends the sensitive period to last more than 1 week via non-genomic mechanisms
      and primes subsequent learning. Even in non-imprinted chicks whose sensitive
      period has ended, exogenous T(3) enables imprinting. Our findings indicate that
      T(3) determines the start of the sensitive period for imprinting and has a
      critical role in later learning.

PMID- 23011136
TI  - Spin-orbit induced electronic spin separation in semiconductor nanostructures.
AB  - The demonstration of quantized spin splitting by Stern and Gerlach is one of the
      most important experiments in modern physics. Their discovery was the precursor
      of recent developments in spin-based technologies. Although electrical spin
      separation of charged particles is fundamental in spintronics, in non-uniform
      magnetic fields it has been difficult to separate the spin states of charged
      particles due to the Lorentz force, as well as to the insufficient and
      uncontrollable field gradients. Here we demonstrate electronic spin separation in
      a semiconductor nanostructure. To avoid the Lorentz force, which is inevitably
      induced when an external magnetic field is applied, we utilized the effective non
      uniform magnetic field which originates from the Rashba spin-orbit interaction in
      an InGaAs-based heterostructure. Using a Stern-Gerlach-inspired mechanism,
      together with a quantum point contact, we obtained field gradients of 10(8) T m(
      1) resulting in a highly polarized spin current.

PMID- 23011137
TI  - Continuous variable quantum key distribution with modulated entangled states.
AB  - Quantum key distribution enables two remote parties to grow a shared key, which
      they can use for unconditionally secure communication over a certain distance.
      The maximal distance depends on the loss and the excess noise of the connecting
      quantum channel. Several quantum key distribution schemes based on coherent
      states and continuous variable measurements are resilient to high loss in the
      channel, but are strongly affected by small amounts of channel excess noise. Here
      we propose and experimentally address a continuous variable quantum key
      distribution protocol that uses modulated fragile entangled states of light to
      greatly enhance the robustness to channel noise. We experimentally demonstrate
      that the resulting quantum key distribution protocol can tolerate more noise than
      the benchmark set by the ideal continuous variable coherent state protocol. Our
      scheme represents a very promising avenue for extending the distance for which
      secure communication is possible.

PMID- 23011138
TI  - Alternative alpha-synuclein transcript usage as a convergent mechanism in
      Parkinson's disease pathology.
AB  - alpha-Synuclein is implicated both in physiological functions at neuronal
      synaptic terminals as well as in pathological processes in the context of
      Parkinson's disease. However, the molecular mechanisms for these apparently
      diverse roles are unclear. Here we show that specific RNA transcript isoforms of
      alpha-synuclein with an extended 3' untranslated region, termed aSynL, appear
      selectively linked to pathological processes, relative to shorter alpha-synuclein
      transcripts. Common variants in the aSynL 3' untranslated region associated with
      Parkinson's disease risk promote the accumulation and translation of aSynL
      transcripts. The presence of intracellular dopamine can further enhance the
      relative abundance of aSynL transcripts through alternative polyadenylation site
      selection. We demonstrate that the presence of the extended aSynL transcript 3'
      untranslated region impacts accumulation of alpha-synuclein protein, which
      appears redirected away from synaptic terminals and towards mitochondria,
      reminiscent of Parkinson's disease pathology. Taken together, these findings
      identify a novel mechanism for aSyn regulation in the context of Parkinson's
      disease-associated genetic and environmental variations.

PMID- 23011139
TI  - A kinase inhibitor screen identifies small-molecule enhancers of reprogramming
      and iPS cell generation.
AB  - Somatic cells can be reprogrammed to form embryonic stem cell-like induced
      pluripotent stem cells (iPSCs), but the process suffers from low efficiency and
      the underlying molecular mechanisms that control reprogramming remain poorly
      understood. Here we perform an inhibitor screen to identify kinases that enhance,
      or present a barrier to, reprogramming. In particular, inhibitors of p38,
      inositol trisphosphate 3-kinase, and Aurora A kinase potently enhance iPSC
      generation, and iPSCs derived from inhibitor-treated somatic cells are capable of
      reaching a fully reprogrammed state. Knockdown of target kinases by short
      interfering RNAs confirms that they function as barrier genes. We show that
      Aurora A kinase, which functions in centrosome activity and spindle assembly, is
      highly induced during reprogramming and inhibits Akt-mediated inactivation of
      GSK3beta, resulting in compromised reprogramming efficiency. Together, our
      results not only identify new compounds that enhance iPSC generation but also
      shed new light on the function of Aurora A kinase in the reprogramming process.

PMID- 23011140
TI  - Quantifying through-space charge transfer dynamics in pi-coupled molecular
      systems.
AB  - Understanding the role of intermolecular interaction on through-space charge
      transfer characteristics in pi-stacked molecular systems is central to the
      rational design of electronic materials. However, a quantitative study of charge
      transfer in such systems is often difficult because of poor control over
      molecular morphology. Here we use the core-hole clock implementation of resonant
      photoemission spectroscopy to study the femtosecond charge-transfer dynamics in
      cyclophanes, which consist of two precisely stacked pi-systems held together by
      aliphatic chains. We study two systems, [2,2]paracyclophane (22PCP) and
      [4,4]paracyclophane (44PCP), with inter-ring separations of 3.0 and 4.0 A,
      respectively. We find that charge transfer across the pi-coupled system of 44PCP
      is 20 times slower than in 22PCP. We attribute this difference to the decreased
      inter-ring electronic coupling in 44PCP. These measurements illustrate the use of
      core-hole clock spectroscopy as a general tool for quantifying through-space
      coupling in pi-stacked systems.

PMID- 23011141
TI  - Computational design of self-assembling register-specific collagen heterotrimers.
AB  - The contribution of pairwise amino-acid interactions to the stability of collagen
      triple helices has remained elusive. Progress in this area is critical for the
      prediction of triple helical stability from sequences and the preparation of
      mimetic materials based on this fold. Here we report a sequence-based scoring
      function for triple helices that takes into account the stability conferred to
      collagen by axial lysine-aspartate salt bridges. This function is used to predict
      the stability of a specific register formed from three distinct peptide sequences
      and that of all alternative compositions and registers. In the context of a
      genetic algorithm we use it to select sequences likely to self-assemble with high
      stability and to the exclusion of the other 26 possible combinations. We validate
      our methodology by synthesis and structural characterization of the designed
      peptides, which self-assemble into a highly stable ABC triple helix with control
      over both composition and register.

PMID- 23011142
TI  - Monodisperse conjugated polymer particles by Suzuki-Miyaura dispersion
      polymerization.
AB  - The self-assembly of colloidal building blocks into complex and hierarchical
      structures offers a versatile and powerful toolbox for the creation of new
      photonic and optoelectronic materials. However, well-defined and monodisperse
      colloids of semiconducting polymers, which would form excellent building blocks
      for such self-assembled materials, are not readily available. Here we report the
      first demonstration of a Suzuki-Miyaura dispersion polymerization; this method
      produces highly monodisperse submicrometer particles of a variety of
      semiconducting polymers. Moreover, we show that these monodisperse particles
      readily self-assemble into photonic crystals that exhibit a pronounced photonic
      stopgap.

PMID- 23011143
TI  - Quasiparticles and Fermi liquid behaviour in an organic metal.
AB  - Many organic metals display exotic properties such as superconductivity, spin
      charge separation and so on and have been described as quasi-one-dimensional
      Luttinger liquids. However, a genuine Fermi liquid behaviour with quasiparticles
      and Fermi surfaces have not been reported to date for any organic metal. Here, we
      report the experimental Fermi surface and band structure of an organic metal
      (BEDT-TTF)(3)Br(pBIB) obtained using angle-resolved photoelectron spectroscopy,
      and show its consistency with first-principles band structure calculations. Our
      results reveal a quasiparticle renormalization at low energy scales (effective
      mass m*=1.9 m(e)) and omega(2) dependence of the imaginary part of the self
      energy, limited by a kink at ~50 meV arising from coupling to molecular
      vibrations. The study unambiguously proves that (BEDT-TTF)(3)Br(pBIB) is a quasi
      2D organic Fermi liquid with a Fermi surface consistent with Shubnikov-de Haas
      results.

PMID- 23011144
TI  - Novel Pauli-paramagnetic quantum phase in a Mott insulator.
AB  - In Mott insulators, the strong electron-electron Coulomb repulsion localizes
      electrons. In dimensions greater than one, their spins are usually ordered
      antiferromagnetically at low temperatures. Geometrical frustrations can destroy
      this long-range order, leading to exotic quantum spin liquid states. However,
      their magnetic ground states have been a long-standing mystery. Here we show that
      a quantum spin liquid state in the organic Mott insulator
      EtMe(3)Sb[Pd(dmit)(2)](2) (where Et is C(2)H(5)-, Me is CH(3)-, and dmit is 1,3
      dithiole-2-thione-4,5-dithiolate) with two-dimensional triangular lattice has
      Pauli-paramagnetic-like low-energy excitations, which are a hallmark of itinerant
      fermions. Our torque magnetometry down to low temperatures (30 mK) up to high
      fields (32 T) reveals distinct residual paramagnetic susceptibility comparable to
      that in a half-filled two-dimensional metal, demonstrating the magnetically
      gapless nature of the ground state. Moreover, our results are robust against
      deuteration, pointing toward the emergence of an extended 'quantum critical
      phase', in which low-energy spin excitations behave as in paramagnetic metals
      with Fermi surface, despite the frozen charge degree of freedom.

PMID- 23011145
TI  - Human adenovirus infection in Kawasaki disease: a confounding bystander?
AB  - BACKGROUND: Human adenovirus (HAdV) infection mimics Kawasaki disease (KD) but
      can also be detected in KD patients. Evidence suggests that HAdV-C species can
      persist in pediatric adenoids and/or tonsils. We sought to determine (1) the
      frequency of HAdV detection by real-time polymerase chain reaction in KD
      patients, (2) the differences in HAdV semiquantitative nasopharyngeal viral loads
      between KD patients with detectable HAdV vs those with HAdV disease, and (3)
      whether nasopharyngeal HAdV-C shedding is occurring in KD. METHODS: From August
      2009 through April 2011, HAdV-positive patients were identified in 1 of the
      following groups: group I, complete or incomplete KD as defined by the American
      Heart Association (AHA); group II, treated for incomplete KD but not fulfilling
      AHA criteria; and group III, otherwise healthy children with some KD-like
      features ultimately diagnosed with HAdV disease. RESULTS: Among 77 KD patients
      diagnosed, 8.8% (5/57) of group I and 25% (5/20) of group II KD patients had HAdV
      detected. Viral loads were significantly lower in group I (n = 5) vs group III (n
      = 26; P = .034). Of the 13 specimens available for HAdV typing, 7 of 7 group III
      and 1 of 3 group II specimens were determined to be HAdV-B using viral culture.
      The remaining 5 KD samples were unable to be cultured and molecular typing showed
      either HAdV-C (n = 3) or were nontypeable (n = 2). CONCLUSIONS: In KD, molecular
      based HAdV detection is not uncommon, may represent persistence of HAdV-C, and
      should be interpreted with caution. Together, quantitative polymerase chain
      reaction and HAdV typing may aid in distinguishing HAdV disease mimicking KD from
      KD with concomitant HAdV detection.

PMID- 23011146
TI  - Editorial commentary: missing the forest for the trees: respiratory viral assays
      in patients with kawasaki disease.

PMID- 23011147
TI  - Impact of the type of diagnostic assay on Clostridium difficile infection and
      complication rates in a mandatory reporting program.
AB  - BACKGROUND: Most Clostridium difficile infection (CDI) surveillance programs
      neither specify the diagnostic method to be used nor stratify rates accordingly.
      We assessed the difference in healthcare-associated CDI (HA-CDI) incidence and
      complication rates obtained by 2 validated diagnostic methods. METHODS: This was
      a prospective cohort study of patients for whom a C. difficile test was ordered
      between 1 August 2010 and 31 July 2011. All specimens were tested in parallel by
      a commercial polymerase chain reaction (PCR) assay targeting toxin B gene tcdB,
      and a 3-step algorithm detecting glutamate dehydrogenase and toxins A and B by
      enzyme immunoassay and cell culture cytotoxicity assay (EIA/CCA). CDI incidence
      rate ratios were calculated using univariate Poisson regression. RESULTS: A total
      of 1321 stool samples were tested during a period totaling 95 750 patient-days.
      Eighty-five HA-CDI cases were detected by PCR and 56 cases by EIA/CCA (P = .01).
      The overall incidence rate was 8.9 per 10 000 patient-days (95% confidence
      interval [CI], 7.1-10.9) by PCR and 5.8 per 10 000 patient-days (95% CI, 4.4-7.4)
      by EIA/CCA (P = .01). The incidence rate ratio comparing PCR and EIA/CCA was 1.52
      (95% CI, 1.08-2.13; P = .015). Overall complication rate was 27% (23/85) when CDI
      was diagnosed by PCR and 39% (22/56) by EIA/CCA (P = .16). Cases detected by PCR
      only were less likely to develop a complication of CDI compared with cases
      detected by both PCR and EIA/CCA (3% vs 39%, respectively; P < .001).
      CONCLUSIONS: Performing PCR instead of EIA/CCA is associated with a >50% increase
      in the CDI incidence rate. Standardization of diagnostic methods may be indicated
      to improve interhospital comparison.

PMID- 23011148
TI  - Recent twin earthquakes in northwest Iran: infectious concerns.

PMID- 23011150
TI  - [Osteoporotic fractures: What is new?].

PMID- 23011149
TI  - [Pathogenesis, classification and diagnosis of necrotizing soft tissue
      infections].
AB  - Necrotizing soft tissue infections are caused by a variety of pathogens and may
      affect different types of soft tissue. Even today mortality and lethality are
      very high. The primary symptoms of necrotizing soft tissue infections are local
      pain out of proportion, swelling, erythema and crepitation in cases of
      subcutaneous gas. A systemic inflammatory response syndrome (SIRS) is often
      associated. During the last decades early recognition and initiation of an
      adequate therapy were able to reduce lethality to an average of 20%. The physical
      examination remains the diagnostic gold standard and may be supported by typical
      findings of imaging technologies, e.g. subcutaneous gas on x-rays and laboratory
      tests. After diagnosis an adequate antibiotic and surgical therapy should be
      performed immediately.

PMID- 23011151
TI  - [Osteoporotic fractures of the distal radius. What is new?].
AB  - The demographic development will result in an increase of up to 30 % of distal
      radius fractures. There are various therapy options but what is new? Conservative
      therapy: conservative therapy is reserved for stable fractures only.
      Osteosynthesis by K-wires: due to low biomechanical stability in older patients,
      insufficient functional and radiological results were achieved. External fixator:
      external fixators are used in compound and complex fractures and show better
      results than K-wire osteosynthesis. Angular stable plate osteosynthesis: with
      angular stable plates it is possible to achieve good results with complex
      fractures and they are currently the method of choice. Intramedullary
      osteosynthesis: intramedullary nails result in a faster functional improvement
      than angular stable plates but have limitations. New is that 90% of osteoporotic
      distal radial fractures are treated with angular stable plates which have shown
      good results in single study groups.

PMID- 23011152
TI  - An unusual cause of macular infarction: protein-losing enteropathy.
AB  - Protein-losing enteropathy is a multisystem disorder characterized by abnormally
      high loss of plasma proteins in the gastrointestinal tract. In addition to loss
      of plasma proteins there is also loss of anticoagulant globulins leading to a
      prothrombotic state in the body. Single case observation. The patient developed
      unilateral macular infarction with non-embolic cerebral infarct due to loss of
      Antithrombin 3 and Protein S proteins in the gastrointestinal tract. The patient
      had poor recovery of vision due to severe ischemic retinal injury. The
      gastroenterology team should be on an alert to rule out prothrombotic states in
      such patients to prevent such complications.

PMID- 23011153
TI  - Tumor autoantibodies as biomarkers for predicting ovarian cancer recurrence.
AB  - Ovarian cancer (OVCA) has a high incidence of recurrence and a high rate of
      mortality. We performed a pilot study to evaluate the usefulness of tumor
      autoantibodies to tumor associated antigens (TAA) to predict OVCA recurrence. A
      validation study with 56 antigens, previously identified in the initial phase of
      the study, along with 13 known tumor antigens on protein arrays was performed on
      an independent cohort of recurrent and non-recurrent OVCA patients. Statistical
      analyses revealed that a panel of 3 antigens predicted recurrence at a median
      time of 9.07 months prior to clinical recurrence in a study population, where
      majority of patients had CA125 values less than 35 U/ml, with an average
      sensitivity, specificity and accuracy of 94.7%, 86.7% and 93.3% respectively. One
      of the top 3 antigens has been associated with the development of polymyositis
      (PM) which has been shown in some cases to precede the occurrence of ovarian
      carcinoma. Our results indicate that these 3 antigens have potential for
      predicting recurrence at an early time and may have better prognostic utility
      than CA125 alone for early therapeutic intervention. These biomarkers could guide
      us to identify those patients that could benefit most from maintenance or
      consolidation therapy.

PMID- 23011154
TI  - Quantitative DNA methylation and recurrence of breast cancer: a study of 30
      candidate genes.
AB  - BACKGROUND: The need for new prognostic factors in breast cancer is ever
      increasing as breast cancer management evolves. Aberrant DNA methylation plays a
      pivotal role in cancer development and progression; DNA methylation-based
      biomarkers may provide independent prognostic information. We used pyrosequencing
      to investigate the prognostic potential of quantitative DNA methylation of a
      large set of candidate genes in a Korean single-institution series of operable
      breast cancer. METHODS: Absolute DNA methylation in 20 candidate genes from an
      initial set of 30 genes was measured by pyrosequencing of bisulfite converted DNA
      in 121 fresh frozen breast cancer cases. Survival analyses used continuous and
      categorized (quintile-based) gene methylation data with time to recurrence (TTR)
      as an endpoint. Prognostic abilities of gene-only and risk-score models were
      explored. RESULTS: Median follow-up was 5.1 years; 25 recurrences (21%) were
      observed. Nodal status, methylation of TWIST1, SLIT2 (both as continuous and
      categorized variables) and APC, HLA-A, NKX2-5, SERPINB5, SFN (as categorized
      variables) were significantly prognostic; grade showed a prognostic trend. A
      multivariate model containing nodal status, grade and TWIST1 was a best fit (p<
      0.001) in stepwise regression; risk-score based on this model separated patients
      into 3 distinct risk-groups (p< 0.001). A gene-only model based on TWIST1 and SFN
      also classified patients into distinct risk-groups (p=0.009). CONCLUSIONS: This
      study shows that accurate quantitative measurement of DNA methylation by
      pyrosequencing identifies a small set of genes with independent prognostic
      potential in breast cancer. These genes complement the current clinico
      pathological prognostic factors and appear to be potential biomarkers that
      warrant further validation.

PMID- 23011155
TI  - Circulating cell-free DNA: a promising marker of regional lymphonode metastasis
      in breast cancer patients.
AB  - PURPOSE: We undertook the current study with untreated breast cancer to (1) role
      the variations in the plasma levels of cfDNA and the size distribution in early
      stage, (2) determine the frequency in plasma of methylation of three candidate
      genes, RASSF1A, MAL, and SFRP1, and (3) to determine whether detection of cfDNA
      variations and methylation changes in plasma might have specific clinical
      utility. METHODS AND MATERIALS: Thirty-nine patients woman patients (median age
      64 years; range, 36-90 years) who underwent surgery for primary BR and 49 healthy
      females' subjects (control group without any breast lesion) were evaluated. The
      cfDNA levels were analyzed using quantitative real-time polymerase chain reaction
      of beta-globin. Based on the ALU repeats, the cfDNA was considered as either
      total (fragments of 115 bp, ALU115) or tumoral (fragments of 247 bp, ALU247). The
      association between the levels of the ALU247, ALU115 repeat, and ALU 247/115and
      the pathologic tumor characteristics was analyzed. Used methylight qPCR method,
      cfDNA from plasma samples of healthy donors and patients with breast cancer were
      evaluated for the diagnotic value of the methylation status of three genes
      (RASSF1A, MAL, SFRP1) frequently methylated in breast cancer. RESULTS: The
      baseline levels of cfDNA were significantly higher in the patients with cancer,
      and the level of ALU247 was the most accurate circulating cfDNA marker in
      discriminating the cancer from non-cancer subjects. A high statistical
      significance was found by considering the T stage and patients with regional LN
      metastasis positive cancers showed significantly higher cfDNA level of ALU247.
      Moreover, patients with methylation of at least one of the gene under investigate
      showed a higher quantity of cfDNA ALU115 (p< 0.0001) and ALU247 level (p<
      0.0001). CONCLUSIONS: We observed that necrosis could be a potential source of
      circulating tumour-specific cfDNA ALU247; and that cfDNA ALU247 and methylated
      cfDNA (RASSF1A, MAL and SFRP1) are both a phenotypic feature of tumour biology.

PMID- 23011156
TI  - MPP3 inactivation by promoter CpG islands hypermethylation in colorectal
      carcinogenesis.
AB  - BACKGROUND: The Drosophila discs large tumor suppressor homologue-3 (MPP3), a
      putative tumor suppressor involved in cell adhesion and cell polarity, is
      frequently inactivated in several carcinomas due to promoter hypermethylation.
      The alteration of MPP3 methylation in colorectal carcinogenesis has not been
      investigated. OBJECTIVE: To determine the role of inactivated MPP3 in colorectal
      tumorigenesis and the potential clinical application as a novel epigenetic
      marker. METHODS: We measured MPP3 mRNA expression and promoter methylation in 6
      colorectal cancer cell lines, 23 primary colorectal carcinomas and corresponding
      non-cancerous tissues. The correlations between MPP3 expression, DNA methylation
      and clinicopathological characteristics were evaluated. RESULTS: Loss of MPP3
      expression was observed in 2 of 6 (33.3%) colorectal cancer cell lines and 10 of
      23 (43.5%) primary colorectal carcinomas. MPP3 promoter hypermethylation also
      occurred in the same colorectal cancer cell lines (SW1116 and LoVo) and 9 of 23
      (39.1%) primary colorectal carcinomas. Among tumors loss of MPP3 mRNA expression,
      the promoter hypermethylation rate was 80%, which was significantly higher than
      tumors with over-expressed MPP3 (7.7%, P=0.001). After treated with 5-aza-dC, two
      cell lines (SW1116 and LoVo) revealed significant restoration of MPP3 expression.
      MPP3 promoter methylation was also significantly higher in advanced colorectal
      carcinoma (57.1%) compared with early stage tumor (11.1%). CONCLUSION: These
      preliminary data suggested that epigenetic inactivation of MPP3 frequently
      occurred during the development of colorectal cancer and might also be a
      potential biomarker for molecular classification of colorectal cancer patients.

PMID- 23011157
TI  - Expression of CDC6 and GDF-9 and their clinicopathological significances in
      benign and malignant lesions of the gallbladder.
AB  - PURPOSE: Gallbladder cancers are cancers with high disease-specific mortality
      rates due to the lack of early diagnosis and effective therapy. In this study, we
      evaluated whether CDC6 and GDF-9 could be a marker for early diagnosis and target
      therapy. METHODS: CDC6 and GDF-9 expressions in 108 gallbladder adenocarcinomas,
      15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral
      tissues were detected using immunohistochemistry (IHC). RESULTS: We demonstrated
      that positive CDC6 and GDF-9 expressions were significantly higher in
      adenocarcinomas than that in peritumoral tissues, polyps, and chronic
      cholecystitis (p < 0.01). Benign lesions with positive CDC6 and negative GDF-9
      expression showed moderately- or severely-atypical hyperplasia. The positive
      rates of CDC6 were significantly lower in cases with well-differentiated
      adenocarcinoma, small tumor mass, no metastasis of the lymph node, and no
      invasion of regional tissues (p < 0.05 or p < 0.01). In contrast, GDF-9
      expression was significantly lower in the cases with poorly-differentiated
      adenocaarcinoma, lymph node metastasis, and invasion (p < 0.05 or p < 0.01).
      Univariate Kaplan-Meier analysis showed that CDC6 (p=0.046) or GDF-9 (p=0.032)
      expression was associated with decreased overall survival. Multivariate Cox
      regression analysis showed that increased expression of CDC6 (p=0.042) or
      decreased expression of GDF-9 (p=0.031) was an independent poor-prognostic
      predictor in gallbladder adenocarcinoma. CONCLUSION: CDC6 and GDF-9 might be
      closely related to the carcinogenesis, clinical biological behaviors, and
      prognosis of gallbladder adenocarcinoma. The positive expression of CDC6 and
      negative expression of GDF-9 have poor-prognosis in gallbladder carcinoma.

PMID- 23011158
TI  - AEG-1 is associated with clinical outcome in neuroblastoma patients.
AB  - Astrocyte elevated gene 1 (AEG-1), a novel gene that was cloned in 2002, has
      emerged in recent years as a potentially crucial mediator of tumor malignancy and
      aberrant elevation of AEG-1 expression frequently occurs in several human
      cancers, including breast cancer, prostate cancer, gastric cancer. However,
      whether AEG-1 deregulation also occurs in neuroblastoma remains unclear. In
      previous study we reported that AEG-1 was over expressed in neuroblastoma cell
      lines and knockdown of AEG-1 inhibits proliferation and enhancing chemo
      sensitivity to cisplatin or doxorubicin in neuroblastoma cells. In this study, we
      investigated the expression of AEG-1 and evaluate its prognostic significance by
      correlating AEG-1 expression levels with clinic pathologic features and survival
      in 32 archived neuroblastoma patients We found that positive AEG-1
      immunoreactivities were present in all neuroblastoma cases, 75% showed high
      expression of AEG-1. And high expression of AEG-1 was commonly seen in vascular
      endothelial cells and glandula in neuroblastoma samples. AEG-1 expression was
      strongly correlated with age at diagnosis (P=0.012), clinical stage (P=0.030) and
      tumor histology stage (P=0.041). However, our analyses did not show significant
      associations between AEG-1 expression and other clinical features including
      gender and primary tumor site. Importantly, our data presented in this report
      provide, for the first time, evidence that elevated expression of AEG-1 protein
      is correlated with poor prognosis and reduced survival of patients with
      neuroblastoma (P= 0.031). Overall, the data support the notion that AEG-1 might
      be used as a biomarker for neuroblastoma patients.

PMID- 23011159
TI  - Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine
      tumors of the lung.
AB  - BACKGROUND: Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion
      region 1 polycomb ring finger (BMI1) are involved in malignant transformation of
      many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their
      expression pattern is largely unknown. This study evaluated their expression in
      96 NELT and correlated it to clinical features including survival. MATERIALS AND
      METHODS: Paraffin embedded material from 50 typical carcinoids (TC), 13 atypical
      carcinoids (AC), 23 large cell neuroendocrine carcinomas (LCNEC) and 10 small
      cell lung carcinomas (SCLC) was evaluated by immunohistochemisty. RESULTS:
      Significantly higher expression of EZH2 was found in high grade NELT (LCNEC +
      SCLC) versus low grade NELT (TC + AC) (p < 0.0001). High expression of BMI1 was
      observed in low grade NELT (TC + AC) in contrast to the expression in high grade
      NELT (LCNEC+SCLC) (p=0.004). In multivariate models, diagnosis was the strongest
      predictor of survival. CONCLUSION: The immunohistochemical expression of EZH2 and
      BMI1 are significantly different in low versus high grade NELT. This difference
      might be related to NELT tumorigenesis. These markers have no independent
      prognostic impact in NELT. Whether EZH2 could become target in new treatments
      strategies against NELT remains to be elucidated.

PMID- 23011160
TI  - The management of rectal cancer with synchronous liver metastases: a modern
      surgical dilemma.
AB  - INTRODUCTION: One in ten patients with rectal cancer presents with synchronous
      colorectal liver metastases. We present an up-to-date review of the different
      surgical strategies available for rectal cancer patients with synchronous
      colorectal liver metastases. METHOD: A literature review of MEDLINE, Cochrane and
      Google scholar was performed. RESULTS: Twenty retrospective studies comparing
      staged versus simultaneous resections were found. Overall survival was similar
      for both approaches whilst the length of stay was decreased in simultaneous
      resections. Only two studies comparing the 'reverse' versus staged or
      simultaneous resections were found. The studies investigating resection versus
      non-resection for rectal primaries with unresectable liver metastases were
      limited. CONCLUSION: Simultaneous resections are a reasonable alternative to
      staged resections for either advanced rectal cancers with limited liver disease
      or early rectal cancers with extensive liver disease. Currently, staged
      resections are favoured over simultaneous resections in patients with locally
      advanced rectal cancers with extensive liver disease. There are too few studies
      to determine the safety of reverse resections in the context of locally advanced
      rectal cancers. A resection of the primary tumour or a non-surgical intervention
      can be justified in the management of the rectal cancer primary in the presence
      of unresectable liver metastases.

PMID- 23011161
TI  - Refractory thrombotic thrombocytopenic purpura associated with primary Sjogren
      syndrome treated with rituximab: a case report.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease that
      involves multiple organs and is rapidly fatal if left untreated. TTP is
      associated with multisystem symptoms, such as thrombocytopenia, microangiopathic
      hemolytic anemia, renal impairment, central nervous system involvement, and
      fever. TTP is idiopathic in about 37% of the cases and can be associated with
      autoimmune diseases in 13% of the cases. Autoimmune disease-associated TTP can be
      refractory to plasma exchange and requires immunosuppressive therapy. We report a
      case of a previously healthy 55-year-old African American female who presented
      with shortness of breath, hemolytic anemia, renal impairment, and
      thrombocytopenia. The diagnosis of TTP was made, and plasmapheresis was
      initiated. However, recurrence happened 48 hours after plasmapheresis was
      stopped. Autoimmune workup for refractory TTP revealed positive antinuclear
      antibodies, Anti-SSA, and Anti-SSB. Lip biopsy revealed findings consistent with
      Sjogren syndrome. Treatment with Rituximab was started, and significant clinical
      and laboratory response was achieved. The patient remained asymptomatic
      thereafter. A high clinical suspicion of autoimmune diseases is important as TTP
      tends to be refractory to plasma exchange in these cases, and immunosuppressive
      therapy is a key. 

PMID- 23011162
TI  - A case report: Multaq-induced leukocytoclastic vasculitis.
AB  - A 71-year-old white male presented to the emergency department complaining of a
      worsening lower extremity rash. Thirteen days before presentation, the patient
      was placed on Multaq (dronedarone) for his paroxysmal atrial fibrillation. Biopsy
      proven leukocytoclastic vasculitis (LV) was diagnosed, and causes for the
      condition other than drug-induced were investigated and ruled out. Rash has been
      cited as a possible side effect of Multaq; however, a literature search has
      revealed this to be the first documented case of likely multaq-induced LV. Other
      patients on Multaq therapy should be monitored for signs and symptoms of LV and
      be referred to an acute care setting as indicated. 

PMID- 23011163
TI  - Cerebral sinovenous thrombosis associated with mastoiditis due to recurrent
      otitis media.
AB  - Cerebral sinovenous thrombosis (CSVT) in childhood is a rare reported. In this
      era of widespread antibiotic use for acute otitis media, the incidence of
      otogenic CSVT has markedly declined but has not been completely prevented. The
      current therapies for CSVT include anticoagulation, thrombolysis, hydration,
      surgery, and supportive care that were based on adult studies, pediatric case
      studies, and expert opinion. We describe the case of a 3-year-old boy who
      presented with manifestations of CSVT associated with mastoiditis secondary to
      otitis media. He completed a 3-month course of combination antibiotic and
      anticoagulation therapy; the CSVT was recanalized, and the mastoiditis had
      partially improved. 

PMID- 23011164
TI  - Obesity genetics: a monopoly game of genes.
AB  - Obesity is a complex disease that affects all ethnic populations worldwide. The
      etiology of this disease is based on the interaction of genetic factors,
      environment and lifestyles indicators. Genetic contribution to the epidemic has
      gained attention from 2 sources: monogenic syndromes that display severe obesity,
      and the polygenic model of common obesity. Single mutations can render a syndrome
      with severe obesity resulting from alteration in central o peripheral appetite
      control mechanisms. The interaction of several polymorphisms and epigenetic
      modifications constitute the basic plot for common obesity, molecular ingredients
      that should not confuse the investigator-they make this riddle even harder to
      decipher. 

PMID- 23011165
TI  - Amisulpride treatment of somatoform disorders: not just chronic fatigue.
AB  - Amisulpride has been used to treat psychotic disorders and more recently even
      chronic fatigue. We describe 2 cases with somatoform disorders and who responded
      to low-dose amisulpride. 

PMID- 23011166
TI  - kappa-opioid receptor activation prevents against arrhythmias by preserving Cx43
      protein via alleviation of intracellular calcium.
AB  - kappa-opioid receptor (kappa-OR) activation with U50,488H, a selective kappa-OR
      agonist, has been previously demonstrated to prevent against cardiac arrhythmias
      via stabilizing the synthesis and degradation of an integral membrane protein,
      Cx43, in gap junctions. However, the exact prevention mechanism remains unclear.
      The present study tested the hypothesis that the kappa OR agonist U50,488H
      mediates the prevention of arrhythmia through the regulation of intracellular
      calcium leading to the preservation of Cx43 protein. By performing
      electrocardiogram monitoring and immunoblotting in isolated Langendorff-perfused
      rat hearts, high concentrations of calcium-perfused rat hearts exhibited
      increased cardiac arrhythmias. Diminished expression of Cx43 protein was
      observed. The utilization of a whole-cell patch clamp technique revealed that
      U50,488H inhibited L-type calcium current in single ventricular myocytes in a
      dose-dependent manner. These effects were blocked by nor-binaltorphimine, potent
      and selective kappa-OR antagonists. Administration of U50,488H before myocardial
      ischemia resulted in an attenuated of total arrhythmia scores. The attenuation
      effect was blocked by nor-binaltorphimine. The attenuation effect was antagonized
      both by Bay K8644, a L-type calcium channel agonist, and also by the Cx43
      uncoupler heptanol. Finally, immunoblotting data demonstrated that the
      preservation of Cx43 protein conferred by U50,488H was reversed in the presence
      of Bay K8644. In summary, the present study demonstrates kappa-OR activation with
      U50,488H may confer antiarrhythmic effects via modulation of the calcium-Cx43
      pathway. 

PMID- 23011167
TI  - Acetylcysteine for acetaminophen overdose in patients who weigh >100 kg.
AB  - N-Acetylcysteine (NAC) dosing for acetaminophen (APAP) overdose is weight based
      (150 mg/kg intravenous or 140-mg/kg oral loading dose) and, in the United States,
      the dosing protocol recommends using a maximum patient weight of 100 and 110 kg,
      respectively. Little clinical data describe the use of NAC for APAP poisoning in
      patients weighing >100 kg. The aim of this study was to describe the
      demographics, outcomes, and adverse event (AE) rates of patients weighing >100 kg
      treated with oral or IV NAC for APAP poisoning. Patients were identified from a
      multicenter retrospective NAC safety study for APAP overdose. We included
      patients with a recorded weight. Trained chart abstractors used a standardized
      form. Selected data included age, gender, weight, serum alanine transaminase, and
      aspartate transaminases, coingestants, NAC administration route, ingestion type,
      AEs, and outcome [hepatotoxicity (alanine transaminase > 1000 U/L), liver
      transplant, or death]. Descriptive statistics were used. Of 503 study patients,
      37 (7.4%) had recorded weights >100 kg. The median (range) weight was 110 kg (101
      160). The median (range) dosing for patients treated with oral NAC was 140 mg/kg
      (127-143 mg/kg) and 150 (108-168) mg/kg for IV NAC. Hepatotoxicity occurred in
      12/36 (33.3%) patients. Death occurred in 4/36 (11.1%) patients. Thirteen NAC
      related AEs occurred in 8 patients (1.6 per person). All AEs were related to NAC
      and were rated nonserious by the reviewer. Clinicians use an actual weight-based
      NAC dose rather than a maximum weight cutoff dose. Hepatotoxicity was common in
      our cohort. AEs were relatively common but not serious. 

PMID- 23011168
TI  - A case of moderate liver enzyme elevation after acute acetaminophen overdose
      despite undetectable acetaminophen level and normal initial liver enzymes.
AB  - Liver function test (LFT) increase is an early sign of acetaminophen (APAP)
      toxicity. Typically, when an acute overdose patient is evaluated and has an
      initial undetectable APAP level and normal liver enzymes, the patient is not
      treated with N-acetylcysteine, and liver enzymes are not expected to increase
      later. We report a case of moderate LFT increase despite normal LFTs and an
      undetectable APAP level after delayed presentation of an APAP ingestion. A 22
      year-old male with no medical history ingested 15-25 hydrocodone/APAP tablets (5
      mg/500 mg). His suicide note and his bunkmate corroborated the overdose time. He
      arrived at the emergency department 16 hours after ingestion. At that time, his
      APAP level was <10 MUg/mL, and his liver enzymes were normal [aspartate
      transaminase (AST) 31 U/L and alanine transaminase (ALT) 34 U/L]. Twenty-nine
      hours after ingestion, the psychiatry team obtained LFTs (AST 45, ALT 61). He had
      persistent nausea and diffuse abdominal pain. On repeat analysis, the APAP level
      at 36 hours was found to be <10 MUg/mL, AST 150, and ALT 204. After 2 more days
      of increasing LFTs and persistent abdominal pain and nausea, the toxicology
      department was consulted, the patient was transferred to the medicine department,
      and intravenous N-acetylcysteine was started 66 hours after ingestion. He was
      treated for 16 hours and had a significant decline in LFTs and symptom
      resolution. His prothrombin time, bilirubin, lactate, creatinine, and mental
      status were normal throughout the admission. Other cases of LFT increase were
      excluded. Our case report illustrates that a moderate increase in liver
      transaminase may occur despite an initial undetectable APAP level and normal
      transaminases after a delayed presentation. In our case, no serious clinical
      effects were reported. 

PMID- 23011169
TI  - Lamotrigine-induced lupus-like syndrome: a case report and literature review.
AB  - Lamotrigine, as a new generation anticonvulsant, has been widely used in treating
      epilepsy. It is also a mood stabilizer for bipolar disorder. Common adverse
      effects include nausea and vomiting, dyspepsia, insomnia, somnolence, and rash.
      However, drug-induced lupus (DIL) due to lamotrigine has been rarely reported. We
      report a case of lupus-like syndrome associated with lamotrigine. A 39-year-old
      male developed arthralgias and positive serum antinuclear antibody repeatedly
      with introductions of lamotrigine. The strong temporal relationship between the
      rheumatological features and drug exposure is illustrative of the disease course
      of DIL. Two hitherto reported lamotrigine-related DIL cases are compared with our
      case. 

PMID- 23011171
TI  - Acanthosis nigricans during treatment with aripiprazole.
AB  - Aripiprazole is typically regarded as a metabolically sparing agent, in contrast
      to other second-generation antipsychotics, which are widely known to lead to
      weight gain and increase the cardiometabolic risk. We report for the first time
      the emergence of Acanthosis nigricans, a dermatological correlate of insulin
      resistance, during treatment with aripiprazole in an adolescent with a family
      history of diabetes mellitus. 

PMID- 23011170
TI  - Use of corticosteroids in early pregnancy is not associated with risk of oral
      clefts and other congenital malformations in offspring.
AB  - Corticosteroids are commonly used to treat inflammatory diseases. There is
      conflicting evidence regarding the association of corticosteroid use in pregnancy
      and congenital malformations in offspring. We conducted a prevalence study of
      83,043 primiparous women who gave birth to a live-born singleton in northern
      Denmark, in 1999-2009. Through medical registries, we identified prescriptions
      for corticosteroids, congenital malformations, and covariates. Furthermore, we
      summarized the literature on this topic. Overall, 1449 women (1.7%) used inhaled
      or oral corticosteroids from 30 days before conception throughout the first
      trimester. Oral cleft in the offspring was recorded for 1 of the users (0.08%)
      and 145 of the nonusers (0.2%), prevalence odds ratio (OR) 0.47 [95% confidence
      interval (CI), 0.07-3.34]. The prevalence OR for congenital malformations overall
      was 1.02 (95% CI, 0.79-1.32). According to published studies, the use of
      corticosteroids in early pregnancy was associated with congenital malformations
      overall with relative estimates ranging from 0.8 (95% CI, 0.4-1.7) to 2.1 (95%
      CI, 0.5-9.6). For oral clefts, the ORs ranged from 0.6 (95% CI, 0.2-1.7) to 5.2
      (95% CI, 1.5-17.1). We found no evidence of an association between use of
      corticosteroids in early pregnancy and risk of congenital malformations in
      offspring. 

PMID- 23011172
TI  - Hyperinsulin therapy for calcium channel antagonist poisoning:  a seven-year
      retrospective study.
AB  - The use of hyperinsulin therapy (HIT) in severe calcium channel antagonist (CCA)
      poisoning has become a more common therapy within the last decade. The objective
      of this study is to report 7 years of experience recommending HIT. This was a
      retrospective chart review utilizing our regional poison center (RPC) data from
      January 1, 2002, through December 31, 2008. All cases of CCA poisoning receiving
      HIT were searched. Endpoints included the number of CCA cases utilizing HIT,
      insulin dose, time of initiation of HIT, patient outcome, adverse events, age,
      glucose concentration, and lowest systolic blood pressure recorded. Forty-six
      cases of CCA poisoning were managed with HIT over 7 years. All the patients
      received standard antidotal therapy (= intravenous fluids, calcium salts,
      glucagon, and pressors). HIT administration followed our RPC recommendation 23
      times (50%), and no hypoglycemic events occurred. Means (age, highest glucose
      measured, and lowest systolic blood pressure measured) were 51 years, 282 mg/dL,
      and 74 mm Hg, respectively. Our RPC recommendations for HIT were followed 50% of
      the time over the last 7 years. In light of the lack of hypoglycemia associated
      with HIT in our study population, we recommend HIT as an early and safe antidote
      in significant CCA poisoning.

PMID- 23011173
TI  - Clinical impact of temporary therapy interruptions on anticoagulation control in
      patients treated with warfarin.
AB  - This retrospective cohort study was completed to describe the impact of short
      term therapy interruptions on anticoagulation control in patients receiving
      warfarin. Patients seen in a pharmacist-managed anticoagulation clinic were
      included if they were on a stable warfarin dose and then underwent a planned
      interruption in therapy. Patients were excluded if phytonadione was administered
      before the interruption or if medications known to interact with warfarin were
      altered during the interruption. Data were analyzed for 2 groups: (1) patients
      with a single interruption in therapy (group 1) and (2) patients with a single
      interruption in therapy plus patients with an extended interruption in therapy
      (group 2). The primary endpoint was the change in weekly maintenance warfarin
      dose from preinterruption to postinterruption. Evaluation of 199 patients
      resulted in 31 interruptions in group 1 and 34 interruptions in group 2. A change
      in dose was required in 58% of patients in group 1 and 56% of patients in group
      2. The mean absolute change in dose was 2.03 +/- 2.79 mg (P < 0.003) in group 1
      and 1.96 +/- 2.72 mg (P < 0.002) in group 2. For the majority of patients, the
      dose change represented <10% of their preinterruption weekly dose. Of patients
      requiring a dose change, 50% required an increase in dose. In conclusion, close
      follow-up is warranted after a warfarin therapy interruption as dose adjustments
      will likely be needed to regain anticoagulation control and the direction of this
      dose change cannot be predicted.

PMID- 23011174
TI  - Carotid intima-media thickness: a target or a marker?
AB  - Evidence-based medicine requires us to use pharmacological agents that have been
      tested and that have been showed to reduce the disease in that particular group
      of affected patients. The choice of the efficacy endpoint is one of the most
      controversial issues in designing the trials. To reduce the high economic costs
      resulting by the large-scale trials design and implementation, the substitution
      of the primary endpoints with a surrogate one, is an optimal opportunity. Carotid
      intima-media thickness is considered an excellent predictor of cardiovascular
      events, and it is also seen as a perfect model of surrogate endpoint for
      pharmacological studies. However, the results from studies using it as a
      surrogate endpoints could lead to erroneous conclusions and could lead marketing
      of products with limited or doubt effectiveness on cardiovascular prevention.
      Studies showed that many interventions targeting the Carotid intima-media
      thickness not impact the final clinical endpoints of interest, whereas low
      density lipoprotein cholesterol level is an excellent biomarker because it can
      predict the cardiovascular outcomes and interventions therapy can efficaciously
      reduce it. 

PMID- 23011175
TI  - Pharmacokinetics of cyclosporine a conversion from twice-daily infusion to oral
      administration in allogeneic hematopoietic stem cell transplantation.
AB  - Twice-daily administration of cyclosporine A (CyA) has often been used for
      prophylaxis of acute graft versus host disease in allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). But there have not been any reports that
      calculated the conversion ratio of the switch from twice-daily intravenous
      infusion to oral administration of CyA in adult patients. To establish the
      conversion ratio and the best strategy of twice-daily administration of CyA, the
      authors investigated the serial changes in the blood CyA concentration during the
      switch from twice-daily intravenous infusion to oral administration while
      maintaining high-peak concentration (over 1000 ng/mL) and calculated the
      bioavailability of Neoral, a micro emulsion cyclosporine, in 11 patients. All the
      patients underwent allo-HSCT with graft versus host disease prophylaxis
      consisting of CyA at a high-peak concentration of twice-daily infusion with short
      term methotrexate and oral administration. Neoral was started at an oral dose, 2
      times daily, at twice the latest dose of intravenous dose according to the
      bioavailability of healthy volunteers. Micafungin, a mild inhibitor of CYP3A4,
      was administered for prophylaxis against fungal infection. The total area under
      the concentration-time curve during oral administration (AUCpo) was nearly the
      same as AUC during intravenous infusion (AUCiv) (mean +/- SD, 7206 +/- 1557
      ng.h.mL and 7783 +/- 897.7 ng.h.mL, respectively). The bioavailability of Neoral,
      defined as F = AUCpo * DOSEiv/AUCiv * DOSEpo was 0.58 +/- 0.15 (mean +/- SD,
      range: 0.41-0.94). When patients were switched from twice-daily infusion to oral
      administration, the dose conversion ratio of 1:2 seemed to be appropriate. At
      that time, the target trough level of Neoral was nearly the same as that of the
      infusion.

PMID- 23011176
TI  - Acetazolamide for the management of chronic metabolic alkalosis in neonates and
      infants.
AB  - In this study, we evaluated the efficacy and safety of acetazolamide in the
      management of chronic metabolic alkalosis in neonates and infants with chronic
      respiratory insufficiency. A retrospective chart review of 90 patients treated
      with acetazolamide between 2006 and 2007 admitted to the neonatal intensive care
      unit was performed. Blood gases and electrolytes obtained at baseline and by 24
      hours after acetazolamide administration were compared. Compared with baseline
      and after 24 hours of acetazolamide, mean measured serum bicarbonate (29.5+/-3.7
      vs. 26.9+/-3.8 mEq/L, P<0.001) and base excess (10.0+/-3.4 vs. 4.8+/-4.0 mEq/L,
      P<0.001) were significantly lower. No significant differences in other
      electrolytes, blood urea nitrogen, and urine output were noted, except for an
      increased serum chloride and creatinine. Uncompensated respiratory acidosis
      developed in 4 (3.1%) treatment courses. Acetazolamide may be effective in
      decreasing serum bicarbonate in carefully selected patients. Its use and safety
      as an adjunctive therapy for chronic metabolic alkalosis in neonates and infants
      with chronic respiratory insufficiency needs further study.

PMID- 23011177
TI  - Evaluating the completeness and accuracy of MedWatch data.
AB  - The Food and Drug Administration's MedWatch system--a voluntary surveillance
      program--received 600,000 adverse event reports on marketed drugs and devices in
      2011. The Food and Drug Administration credits the MedWatch system with improving
      awareness, and expediting early detection, of drug and device risks and in
      illuminating the adoption of medical treatments. Reporting bias has been
      acknowledged as a limitation of the MedWatch system. No systematic assessment of
      the accuracy and completeness of adverse event reporting has been conducted, yet
      inaccurate adverse event reporting may lead drug safety professionals to draw
      incorrect conclusions, manufacturers may be wrongly forced to suspend and
      withdraw medications and interventions, health professionals may mistakenly alter
      their clinical practices, and patients may be denied safe and effective
      treatments. In 2011, the Tufts Center for the Study of Drug Development gathered
      and analyzed 10.2 million adverse event reports filed with the MedWatch system.
      Patient information was generally complete and accurate. Suspect product
      information, on the other hand, showed high levels of incomplete and inaccurate
      data. Start and end dates of suspect product use had 37% and 23% completion
      rates, respectively. Dosage level was completed only 31% of the time, and product
      lot numbers had only a 9% completion rate. More than 25% of the names of reported
      suspect products were inaccurate, and 31% of suspect product start dates were
      inaccurate. Higher levels of completion and accuracy were associated with reports
      filed closer to the date when the adverse event was observed. Implications of the
      results and suggested improvements are discussed.

PMID- 23011178
TI  - Food and Drug Administration approval of cetuximab and a new KRAS genetic test
      for metastatic colorectal cancer: major advance but just the tip of the biomarker
      iceberg.

PMID- 23011179
TI  - Time resolved EPR of [70]fullerene monoadducts in the photoexcited triplet state.
AB  - Triplet excited states of isomers alpha, beta and gamma of N-methyl
      [70]fulleropyrrolidine in glassy toluene (T = 120 K) are investigated with Time
      Resolved EPR (TR-EPR) spectroscopy using pulsed laser photoexcitation. Both the
      zero field splitting (ZFS) parameters D, E and the anisotropic triplet population
      rates are measured. Results reveal a strong dependence of the triplet state
      wavefunction on the position (alpha, beta or gamma) of the pyrrolidine addend
      with respect to the pole of the [70]fullerene unit. The relevant molecular
      orbitals have been calculated giving support to this finding. The dipolar tensor
      principal axes are located at the molecular reference frame from the inspection
      of the EPR spectra in a frozen liquid crystal (E7). Time evolution of the triplet
      EPR signals is different among the isomers, suggesting different triplet
      lifetimes and/or spin relaxation properties. The spin-density distribution in the
      first triplet state for N-methyl-[70]fulleropyrrolidine is compared with that
      previously observed for pristine C(70).

PMID- 23011180
TI  - DAPK plays an important role in panobinostat-induced autophagy and commits cells
      to apoptosis under autophagy deficient conditions.
AB  - The histone deacetylase inhibitor (HDACi) LBH589 has been verified as an
      effective anticancer agent. The identification and characterization of new
      targets for LBH589 action would further enhance our understanding of the
      molecular mechanisms involved in HDACi therapy. The role of the tumor suppressor
      death-associated protein kinase (DAPK) in LBH589-induced cytotoxicity has not
      been investigated to date. Stable DAPK knockdown (shRNA) and DAPK overexpressing
      (DAPK+++) cell lines were generated from HCT116 wildtype colon cancer cells.
      LBH589 inhibited cell proliferation, reduced the long-term survival, and up
      regulated and activated DAPK in colorectal cancer cells. Moreover, LBH589
      significantly suppressed the growth of colon tumor xenografts and in accordance
      with the in vitro studies, increased DAPK levels were detected
      immunohistochemically. LBH589 induced a DAPK-dependent autophagy as assessed by
      punctuate accumulation of LC3-II, the formation of acidic vesicular organelles,
      and degradation of p62 protein. LBH589-induced autophagy seems to be
      predominantly caused by DAPK protein interactions than by its kinase activity.
      Caspase inhibitor zVAD increased autophagosome formation, decreased the cleavage
      of caspase 3 and PARP but didn't rescue the cells from LBH589-induced cell death
      in crystal violet staining suggesting both caspase-dependent as well as caspase
      independent apoptosis pathways. Pre-treatment with the autophagy inhibitor
      Bafilomycin A1 caused caspase 3-mediated apoptosis in a DAPK-dependent manner.
      Altogether our data suggest that DAPK induces autophagy in response to HDACi
      treatment. In autophagy deficient cells, DAPK plays an essential role in
      committing cells to HDACi-induced apoptosis.

PMID- 23011181
TI  - Mod(mdg4) participates in hormonally regulated midgut programmed cell death
      during metamorphosis.
AB  - The insect midgut undergoes programmed cell death (PCD) during metamorphosis, but
      the molecular basis for this phenomenon has not been demonstrated. We report a
      mod(mdg4) protein [designated as mod(mdg4)1A] that is involved in hormonally
      regulated insect midgut PCD, from the lepidopteran Helicoverpa armigera.
      Mod(mdg4)1A is localized in the larval midgut and is highly expressed during
      metamorphosis. Knockdown of mod(mdg4)1a by feeding dsRNA to the larvae suppressed
      midgut PCD and delayed metamorphosis. The mechanism is that mod(mdg4)1a knockdown
      decreased the transcript levels of genes involved in PCD and metamorphosis, but
      increased the transcript level of inhibitor of apoptosis survivin. The transcript
      level of mod(mdg4)1a is independently upregulated by 20-hydroxyecdysone (20E) or
      juvenile hormone (JH) analog methoprene. Overlapped 20E and methoprene
      counteractively regulate the transcript level of mod(mdg4)1a. 20E upregulates the
      mod(mdg4)1a transcript level not through its nuclear receptor EcRB1. Methoprene
      upregulates the mod(mdg4)1a transcript level through the juvenile hormone
      candidate receptor Met. These findings indicate that mod(mdg4)1a participates in
      midgut PCD and metamorphosis by regulating the transcript levels of a network of
      genes via different pathways under 20E and JH regulation.

PMID- 23011183
TI  - A domino synthetic strategy leading to two-carbon-tethered fused acridine/indole
      pairs and fused acridine derivatives.
AB  - A series of new poly-functionalized two-carbon-tethered fused acridine/indole
      pairs were synthesized via Bronsted acid-promoted domino reactions between
      indoline-2,3-dione and C(2)-tethered indol-3-yl enaminones. The reactions were
      further expanded to prepare C-tethered fused acridine/pyridine pairs, N
      substituted amino acids, N-cyclopropyl and N-aryl substituted fused acridine
      derivatives, as well as bis-furan-3-yl-substituted indoles. During these reaction
      processes, the domino construction of a fused acridine skeleton with concomitant
      formation of two new rings was readily achieved in a one-pot operation. The
      procedures are facile, avoiding time-consuming and costly syntheses, tedious work
      up and purification of precursors.

PMID- 23011184
TI  - Cerebrovascular accidents in patients treated for choroidal neovascularization
      with ranibizumab in randomized controlled trials.
AB  - PURPOSE: To analyze cerebrovascular accidents (CVAs) pooled from large,
      randomized, controlled clinical trials of ranibizumab treatment for neovascular
      age-related macular degeneration. METHODS: Events in five trials (FOCUS, MARINA,
      ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring
      process. Exact methods, stratified by study, were used to test for treatment
      differences based on odds ratios. A stepwise logistic regression model was fit to
      classify subjects' risk for CVA based on medical history. Treatment differences
      in CVA rates at 1 year or 2 years were evaluated within risk groups using
      stratified exact methods. RESULTS: Pooled 2-year CVA rates were <3%; odds ratios
      (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg
      versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for
      0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg
      versus 0.3 mg was identified in pooled analyses or any of the individual trials.
      In pooled analyses, the difference between 0.5-mg ranibizumab and control was
      larger (7.7 [1.2-177]) among high-risk CVA patients. CONCLUSION: This analysis
      provided some evidence, although not definitive, of a potential increased risk of
      CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab.
      Continued monitoring for CVA within clinical trials seems warrented.

PMID- 23011185
TI  - Author response: Nonspecific PCR amplification of CRYBB2-pseudogene leads to
      misconception of natural variation as mutation.

PMID- 23011186
TI  - Direct observation of one-dimensional plasmon coupling in metallic nanofibers
      prepared by evaporation-induced self-assembly with DNA.
AB  - Here we report a simple method for the preparation of highly aligned metallic
      nanofibers with anisotropic aggregates of silver nanoparticles (AgNPs) as well as
      a direct observation of localized plasmon field and its coupling in the prepared
      metallic nanofibers. Metallic nanofibers of several tens of nanometers wide and
      millimeters long were prepared. The preparation method, which is based on the
      process of evaporation-induced self-assembly with DNA and drying front movement,
      eliminates the need for lithography and an external field, and it is fast, cheap
      and easy. Dark-field scattering spectroscopy was used to study the strong plasmon
      coupling of AgNPs in the metallic nanofibers. We observed strong near-field
      coupling between neighboring nanoparticles, which results in red-shifted
      multipolar plasmon modes that are highly polarized along the fiber axis. The
      polarization dependence of plasmon coupling in the metallic nanofibers observed
      in this study was satisfactorily explained by the morphology of the metallic
      nanofibers, which was characterized by atomic force microscopy (AFM) and scanning
      electron microscopy (SEM). Furthermore, Raman spectra imaging of the metallic
      nanofibers revealed the existence of intense hot spots localized along their
      axes, which played a significant role in the intensity of surface enhanced Raman
      scattering (SERS) signals from DNA bases in the metallic nanofiber. Our results
      demonstrate the use of evaporation-induced self-assembly with DNA as a
      straightforward method to produce one-dimensional coupling of localized plasmons
      with a longer scale.

PMID- 23011187
TI  - Peripheral zone prostate cancer localization by multiparametric magnetic
      resonance at 3 T: unbiased cancer identification by matching to histopathology.
AB  - OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of
      peripheral zone prostate cancer localization by multiparametric magnetic
      resonance (MR) at 3 T using segmental matching of histopathology and MR images to
      avoid bias by image features in selection of cancer and noncancer regions.
      MATERIALS AND METHODS: Forty-eight patients underwent multiparametric MR imaging
      (MRI) on a 3 T system using a phased array body coil and spine coil elements for
      signal detection before prostatectomy. The examination included T2-weighted
      imaging (T2WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced
      imaging (DCE-MRI), and MR spectroscopic imaging (MRSI). Histopathology slides
      were correlated to T2W images and a stringent matching procedure was performed to
      define cancer and noncancer areas of the peripheral zone without influence of the
      MR image appearance. Mean T2W signal intensity, apparent diffusion coefficient,
      area under the enhancement curve, and choline + creatine-to-citrate signal ratio
      were calculated for cancer and noncancer areas. Receiver operating characteristic
      (ROC) analysis was performed on MR-derived parameters from the selected areas.
      Logistic regression was used to create models based on best combination of
      parameters. A simplified approach assigning a parametric score to each segment
      based on cutoff values from ROC analysis was also explored. RESULTS: By using the
      stringent matching procedure, 138 noncancer and 41 cancer segments were selected
      in the T2W images and transferred to the images of the other MR methods. A
      significant difference between mean values in cancer and noncancer segments was
      observed for all MR parameters analyzed (P < 0.001). Apparent diffusion
      coefficient was the best performing single parameter, with an area under the ROC
      curve Az,DWI of 0.90 for prostate cancer detection. Any combination of T2WI, DWI,
      and DCE-MRI was significantly better than T2WI alone in separating cancer from
      noncancer segments (Az,T2WI + DWI + DCE-MRI = 0.94, Az,T2WI + DWI = 0.92, Az,T2WI
      + DCE-MRI = 0.91, Az,T2WI = 0.85). The combination of T2WI and MRSI was also
      better than T2WI alone (Az, T2WI + MRSI = 0.90); however, the logistic regression
      models including MRSI did not have significant parameters. The simplified
      approach combining all parameters gave similar results to logistic regression
      combining all parameters (Az = 0.95 and 0.97, respectively). CONCLUSION: By
      selecting histopathology defined cancer and noncancer areas without influence of
      image contrast, this study objectively reveals that all investigated MR
      parameters have the ability to separate cancer from noncancer areas in the
      peripheral zone individually and that any combination is better than T2WI alone.

PMID- 23011188
TI  - Toxicological safety evaluation of gadobutrol.
AB  - OBJECTIVES: Gadobutrol (Gadovist/Gadavist, Bayer Pharma AG, Berlin, Germany) is a
      nonionic, macrocyclic, gadolinium-based contrast agent for magnetic resonance
      imaging of the central nervous system as well as liver and kidneys and for
      contrast enhancement in magnetic resonance angiography. For risk assessment of
      the single diagnostic use in humans, the toxicity of this compound was evaluated
      with a series of preclinical studies. MATERIALS AND METHODS: Preclinical studies
      into acute, repeated-dose, reproductive, and developmental toxicity as well as
      genotoxicity, local tolerance, contact-sensitizing potential, and antigenicity
      were performed. RESULTS: In rodents, lethality was observed after a single
      intravenous administration of 20 mmol/kg, representing doses at least 2 orders of
      magnitude higher than the standard single diagnostic dose in humans (0.1
      mmol/kg). The no observed adverse effect levels after repeated (daily)
      administrations over the course of 4 weeks exceeded the single diagnostic dose in
      humans by a factor of 12 in rats and 10 in dogs (calculated on the basis of body
      weight), and no unexpected organ toxicity was observed. The most salient finding
      of repeated dosing in both rats and dogs was vacuolization of renal tubular
      epithelium without concomitant effect on kidney function, which represents a well
      known finding for this class of compounds. Gadobutrol was not teratogenic in
      rats, rabbits, and monkeys even when given repeatedly during organogenesis at
      maximum dose levels tested, being 25 to 100 times (based on body weight) above
      the diagnostic dose in humans. No indications of potential genotoxic, contact
      allergenic, or immunotoxic effects were observed. In local tolerance testing,
      gadobutrol was well tolerated after intravenous administration. CONCLUSIONS:
      Gadobutrol was well tolerated with high safety margins between the single
      diagnostic dose of 0.1 mmol/kg in humans and the doses showing effects in animal
      studies.

PMID- 23011189
TI  - Clinical and histologic implications of delayed hepatobiliary enhancement on
      magnetic resonance imaging with gadolinium ethoxybenzyl
      diethylenetriaminepentaacetic Acid.
AB  - PURPOSE: The aim of this study was to evaluate the serial signal changes in
      hepatobiliary enhancement on gadolinium ethoxybenzyl
      diethylenetriaminepentaacetic acid or gadoxetic acid (Gd-EOB-DTPA)-enhanced
      magnetic resonance imaging and its correlation with clinical parameters. METHOD:
      Under institutional review board approval, Gd-EOB-DTPA-enhanced magnetic
      resonance imaging was performed in 77 subjects (21 healthy volunteers and 56
      biopsy-proven chronic hepatitis patients), and the signal intensities of the
      liver and common hepatic ducts (CHD) were measured every 2 minutes up to 50
      minutes postcontrast. The associations among hepatic and CHD signals,
      physiological and hematological variables, histological activity index, and
      Metavir scores were analyzed with Pearson correlation and multiple linear
      stepwise regressions. The predictive ability of contrast enhancement index (CEI)
      of the liver with histological activity index and fibrosis scores at different
      time points were studied using nonparametric receiver operating characteristic
      curves. RESULTS: Among the clinical parameters, body weight and body mass index
      had the highest negative correlation with hepatobiliary enhancement between 2 and
      50 minutes postcontrast (P < 0.001). Multiple regressions showed that creatinine
      level, body weight, and body mass index were independent predictors for both mean
      hepatic and CHD signal intensity (P < 0.05). Patients with more severe fibrosis
      or moderate necrosis tended to have lower CEIs than other patients were. The
      predictive ability of CEI for the best differentiation between no fibrosis and
      any fibrosis (F >= 1) was at 10 minutes postcontrast (area under the receiver
      operating characteristic curve, 0.797). CONCLUSIONS: Delayed hepatobiliary
      enhancement with Gd-EOB-DTPA could be possibly used for staging liver fibrosis.
      Contrast enhancement index of the liver at 10 minutes is useful for
      differentiating between no fibrosis and any degree of fibrosis in chronic
      hepatitis patients.

PMID- 23011190
TI  - D-pi-A-pi-D type benzothiadiazole-triphenylamine based small molecules containing
      cyano on the pi-bridge for solution-processed organic solar cells with high open
      circuit voltage.
AB  - Two novel D-pi-A-pi-D structured small molecules composed of benzothiadiazole and
      triphenylamine were designed and synthesized.  with cyano on the pi-bridge
      exhibited a deep HOMO energy level, resulting in an impressive V(OC) of up to
      1.04 V with a PCE of 3.85%, while non-cyano substituted  yielded a V(OC) of 0.94
      V and a PCE of 1.99%.

PMID- 23011191
TI  - Choices doctors would make if their infant had hypoplastic left heart syndrome:
      comparison of survey data from 1999 and 2007.
AB  - Data suggest that despite improved surgical outcomes for infants with hypoplastic
      left heart syndrome (HLHS), the past two decades have seen little change in
      parents' decisions whether to choose surgery or palliative treatment without life
      prolonging intervention. Data also suggest that doctors' predictions of the
      choices they would make if their own infant were diagnosed with HLHS do not
      correlate with their predictions of surgical outcomes. Although previous studies
      have compared rates of surgery and palliative treatment without life-prolonging
      intervention over time, no studies have assessed changes in doctors' attitudes.
      The current study used descriptive and quantitative statistics to compare
      responses from American pediatric cardiologists and congenital cardiac surgeons
      from studies conducted in 1999 and 2007. These doctors were asked what choice
      they believe they would make for their own affected infant. Comparison of
      responses from 1999 and 2007 showed no difference in the responses of
      cardiologists: 1999 (44 % surgery, 17 % palliative treatment, 40 % uncertain)
      versus 2007 (45 % surgery, 20 % palliative treatment, 35 % uncertain). Among
      surgeons, there was a non-statistically significant trend away from choosing
      surgery: 1999 (77 % surgery, 5 % palliative treatment, 18 % uncertain) versus
      2007 (56 % surgery, 8 % palliative treatment, 36 % uncertain). In conclusion,
      these analyses suggest that despite improving surgical outcomes, doctors are no
      more likely to predict that they would choose surgery for their own hypothetical
      infant with HLHS. Further research is needed to determine what factors influence
      choice making in the care of infants with HLHS.

PMID- 23011192
TI  - Left thoracoscopic sympathectomy used as primary therapy for a young child with
      intractable long QT syndrome.
AB  - A 3-year-old boy with familial long QT syndrome type 2 presented with recurrent
      syncope despite adequate beta-blocker therapy. Two family members had experienced
      sudden cardiac arrest, and one other relative had experienced sudden cardiac
      death. Given the high risk for ventricular arrhythmia/syncope, the decision was
      made to perform primary cardiac denervation therapy through a minimally invasive
      approach without concomitant automatic cardioverter-defibrillator implantation.
      Using video-assisted thoracoscopic surgery, the left-sided sympathetic ganglia
      from T2-T5 were identified, and dissection along the sympathetic chain with
      transection of the corresponding rami along T2-T5 in addition to the lower half
      of the stellate ganglion was performed. The chest tube was removed on day 1 after
      surgery, and the patient was discharged on postoperative day 4. During 14 months
      of follow-up evaluation, no intervening episodes of ventricular arrhythmia or
      syncope and no symptoms of Horner's syndrome were noted.

PMID- 23011193
TI  - Minimally-invasive coronary artery bypass grafting.

PMID- 23011194
TI  - Questioning the cost-benefit ratio of the telecardiology service in the state of
      Minas Gerais.

PMID- 23011195
TI  - Parasympathetic impairment in the preclinical stage of chronic Chagas disease.

PMID- 23011196
TI  - Case 6/2012: newborn with pulmonary atresia, ventricular septal defect and double
      aortic arch.

PMID- 23011197
TI  - ST-segment elevation in pulmonary thromboembolism.

PMID- 23011198
TI  - Sinus bradycardia persisting for 9 days after carotid angioplasty and stenting.

PMID- 23011199
TI  - Controllable growth of triangular hexagonal boron nitride domains on copper foils
      by an improved low-pressure chemical vapor deposition method.
AB  - We demonstrate an improved low-pressure chemical vapor deposition method to
      fabricate hexagonal boron nitride (h-BN) domains of a few layers (one-four
      layers) from ammonia borane by adding a small quartz tube to stabilize the gas
      flow over the copper substrate and reducing the growing rate of h-BN. The h-BN
      grows freely and spontaneously to form triangular domains on the Cu (100) plane.
      The triangular domains are prone to be parallel to each other on the copper
      substrate. The h-BN domains grow by extending in the normal direction of the
      triangle and form a large thin film by joining together. Both the size and
      coverage rate on Cu foils are well controlled by tuning the amount of ammonia
      borane.

PMID- 23011200
TI  - HIZ's relation to axial load and low back pain: investigated with axial loaded
      MRI and pressure controlled discography.
AB  - PURPOSE: The aims were to investigate if the detection of high-intensity zones
      (HIZ) is affected by axial load, and to study the correlation between HIZ and
      discogenic pain provoked with pressure controlled discography (PCD). METHODS: 41
      consecutive patients with chronic low back pain, referred for discography, were
      included. Each patient underwent PCD, CT, MRI, and axial loaded MRI (alMRI)
      within 24 h. 35 patients completed all MRI sequences (140 discs). The detection
      of HIZ was compared between conventional MRI and alMRI. PCD was performed in 119
      of the discs examined at MRI. Provoked pain at PCD was classified into four
      categories (none/unfamiliar/similar/exact), with the patients' daily pain as
      reference, and correlated with presence of HIZ. RESULTS: AlMRI did not affect the
      detection of HIZ compared with conventional MRI. No significant correlation
      between HIZ and the 4-graded pain response at discography was found (p = 0.34),
      neither when combining similarly/exactly reproduced pain (p = 0.08). The
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of HIZ in detecting discs with exactly reproduced pain were 49, 69,
      39 and 76 %. When combining similarly/exactly reproduced pain, PPV was higher but
      still only 70 %. CONCLUSIONS: The detection of HIZ was not influenced by axial
      load. With strict PCD, discogenic pain can neither be confirmed when having HIZ
      (PPV 39 %) nor ruled out in discs without HIZ (NPV 76 %). Larger PCD studies
      including quantification of HIZ at conventional and alMRI are needed, before any
      dynamic component affected by axial load can be ruled out completely.

PMID- 23011201
TI  - The impact of internal or external transanastomotic pancreatic duct stents
      following pancreaticojejunostomy. Which one is better? A meta-analysis.
AB  - BACKGROUND: The use of pancreatic duct stent to improve postoperative outcomes of
      pancreatic anastomosis remains a matter of debate, and the value of stenting when
      performing anastomosis for normal pancreas (soft and duct less than 3 mm) needs
      further study. The aim of the present meta-analysis was to evaluate the
      perioperative outcomes of patients with stenting during pancreatic anastomosis
      and compare the effect of external stent with that of internal stent indirectly.
      METHODS: A systematic literature search (EMBASE, MEDLINE, PubMed, The Cochrane
      Library, and Web of Science) was performed to identify studies evaluating
      external stent or internal stent. Included literature was assessed and extracted
      by two independent reviewers. A meta-analysis including comparative studies
      providing data on patients with and without external stenting or internal
      stenting during pancreaticojejunostomy anastomosis was performed. RESULTS:
      Thirteen articles including 1,867 patients were identified for inclusion: five
      randomized controlled trials study and eight observational clinical studies. Meta
      analyses revealed that use of external stent was associated with a significantly
      decreased risk for pancreatic fistula in total (odds ratio (OR) 0.47; 95 %
      confidence interval (CI) 0.31-0.71; P = 0.0004; I (2) = 3 %), pancreatic fistula
      in normal pancreas(OR 0.5; 95 % CI 0.30-0.82; P = 0.007; I (2) = 5 %), and
      overall morbidity(OR 0.64; 95 % CI 0.45-0.90; P = 0.01; I (2) = 0 %); however,
      the meta-analysis showed that there were no significant differences between
      internal stenting and non-stenting groups as regards perioperative outcomes and
      that in fact it may increase pancreatic fistula rate in normal pancreas(OR 1.97;
      95 % CI 1.05-3.69; P = 0.03; I (2) = 0 %). CONCLUSIONS: The results of this
      analysis demonstrate a trend toward reduced pancreatic fistula with the use of
      external pancreatic stents in pancreaticojejunostomy. An internal stent does not
      impact development of fistula and that in fact it was not useful in a soft
      pancreas. Our conclusion may be limited to stenting during the duct-to-mucosa
      pancreaticojejunostomy anastomosis, and the value of stenting during invagination
      anastomosis needs further study.

PMID- 23011202
TI  - Persistent perforation in non-faeculant diverticular peritonitis--incidence and
      clinical significance.
AB  - BACKGROUND: Non-resectional strategies (NRS) have improved outcomes for a sub
      group of patients with perforated diverticulitis. NRS are applicable to patients
      with non-faeculant peritonitis (Hinchey II and III). Success is dependent on the
      initial perforation sealing, which Hinchey estimated occurred 'most of the time'.
      An exact percentage remains ill-defined. OBJECTIVE: We aimed to define the
      percentage and clinical significance of a persistent perforation in non-faeculant
      diverticular peritonitis. DESIGN: A retrospective review was conducted of all
      patients admitted with a diagnosis of perforated diverticulitis between January
      1999 and July 2010. Patients undergoing an emergency operation were analysed
      according to Hinchey and physiological and operative severity scores and compared
      with histological findings. RESULTS: One hundred fifteen patients were
      identified. Fifty-three patients underwent a 'resectional' procedure. At surgery,
      15 patients had faeculent peritonitis, 27 patients had purulent peritonitis and
      11 patients had a contained abscess. Of the patients with non-faeculant
      peritonitis, 2/9 (22.2 %) Hinchey II and 10/27 (37.1 %) Hinchey III patients had
      persistent perforation on review of histology. Persistent perforation was
      associated with a significant increase in morbidity, length of stay,
      physiological and operative severity score (p = 0.015, 0.011, 0.049 and 0.002,
      respectively). CONCLUSION: A proportion of patients with non-faeculant
      peritonitis have a persistent perforation which is associated with a poorer
      outcome and is likely to result in failure of a non-resectional management
      strategy. Updated classification systems and tailored peri-operative
      investigations are required to identify this sub-group of patients and improve
      patient outcomes.

PMID- 23011203
TI  - Procedure for calculation of potency and efficacy for ligands acting on Gs- and
      Gi-coupled receptors.
AB  - Structure activity relationship (SAR) analyses of pharmacological data of
      compounds constitute an important part of the discovery process in the design of
      new drug candidates with improved pharmacological properties. In particular G
      Protein Coupled Receptors (GPCRs) associated with the cAMP second messenger
      systems G(s) and G(i) have constituted one of the most widely used basis for
      pharmacological in vitro assays for assessing functional receptor effects. Such
      assays are based on Radio Immuno Assay (RIA) analysis to measure the cellular
      cAMP concentration as readout of receptor activation. It appears, however, to be
      a common practice to omit the use of cAMP standard curves to transform the
      measured signals (cpm or cps) into cAMP concentrations on which estimations of
      potencies (EC(50) values) and efficacies (E(MAX) values) in G(s) and G(i) coupled
      receptor stimulation are based. Such practice may lead to significant errors as
      compounds mediating their effects via G(s) coupled receptors may appear more
      potent and efficacious than they actually are. Contrary, compounds mediating
      their effects via G(i) coupled receptors may appear less potent and efficacious
      than they are in reality. Potency rank orders will therefore change considerably,
      when estimations are based on incorrect calculation of the original experimental
      results. Thus, the only correct way to calculate effect data on which to base
      E(MAX) and EC(50) estimations is to use cAMP concentrations derived from
      transformation of the measured signals (cpm or cps) using cAMP standard curves.
      The present work outlines the mathematical procedures by which such
      transformations are to be performed.

PMID- 23011204
TI  - Poloxamer-188 attenuates TBI-induced blood-brain barrier damage leading to
      decreased brain edema and reduced cellular death.
AB  - Plasmalemma permeability plays an important role in the secondary neuronal death
      induced by traumatic brain injury (TBI). Previous works showed that Poloxamer 188
      (P188) could restore the intactness of the plasma membrane and play a
      cytoprotective action. However, the roles of P188 in blood-brain barrier (BBB)
      integrity and TBI-induced neural cell death are still not clear. In this study,
      mice were induced TBI by controlled cortical impact (CCI), and cerebral water
      content was measured to explore the profile of brain edema after CCI. Further,
      the regimen of P188 in mouse CCI models was optimized. The neurological test and
      BBB integrity assessment were performed, and the numbers of TBI-induced neural
      cell death were counted by propidium iodide (PI) labeling. The expression of
      apoptotic pathway associated proteins (Bax, cyt-c, caspase-8, caspase-9, caspase
      3, P53) and aquaporin-4 (AQP4) was assessed by RT-PCR or immunoblotting. The data
      showed that the brain edema peaked at 24 h after TBI in untreated animals. Tail
      intravenous injection of P188 (4 mg/ml, 100 MUl) 30 min before TBI or within 30
      min after TBI could attenuate TBI-induced brain edema. P188 pre-treatment
      restored BBB integrity, suppressed TBI-induced neural cell death, and improved
      neurological function. TBI induced an up-regulation of Bax, cyt-c, caspase-8,
      caspase-9, caspase-3, and the expression of p53 was down-regulated by P188 pre
      treatment. AQP4 mainly located on endothelial cells and astrocytes, and its
      expression was also regulated by P188 pretreatment. All these results revealed
      that P188 attenuates TBI-induced brain edema by resealing BBB and regulating AQP4
      expression, and suppressed apoptosis through extrinsic or intrinsic pathway.
      Plasmalemma permeability may be a potential target for TBI treatment.

PMID- 23011205
TI  - The age-related gliosis and accompanying deficit in spatial learning are
      unaffected by dimebon.
AB  - A non-selective antihistamine, dimebon, has recently emerged as a potential
      treatment for Alzheimer's disease and Huntington's disease. Dimebon exerts
      several effects in addition to its anti-histaminergic effect, and of particular
      interest is its ability to enhance cognitive function in several models. The
      mechanism underlying this is unknown though it has been suggested that it may be
      associated with its anti-cholinergic action. Dimebon has also been reported to be
      neuroprotective, perhaps as a result of its ability to stabilize mitochondria. We
      considered that these effects might impact on the well-described age-related
      impairment in spatial learning and therefore examined the effect of repeated
      administration of dimebon on performance of young and aged animals in the Morris
      water maze. Whereas a clear age-related deficit was observed, dimebon failed to
      exert any effect on performance. Similarly, dimebon exerted no effect on the age
      related increase in hippocampal expression of several markers of microglial and
      astroglial activation. We conclude that, despite its cognitive enhancing effects
      in some models, dimebon failed to modulate the deficit in spatial learning in
      aged rats and the evidence suggests that the drug does not possess anti
      inflammatory properties.

PMID- 23011206
TI  - PARP-1 inhibitors DPQ and PJ-34 negatively modulate proinflammatory commitment of
      human glioblastoma cells.
AB  - Poly(ADP-ribose) polymerases (PARPs) are recognized as key regulators of cell
      survival or death. PARP-1 is essential to the repair of DNA single-strand breaks
      via the base excision repair pathway. The enzyme may be overactivated in response
      to inflammatory cues, thus depleting cellular energy pools and eventually causing
      cell death. Accordingly, PARP-1 inhibitors, acting by competing with its
      physiological substrate NAD(+), have been proposed to play a protective role in a
      wide range of inflammatory and ischemia/reperfusion-associated diseases.
      Recently, it has also been reported that PARP-1 regulates proinflammatory
      mediators, including cytokines, chemokines, adhesion molecules, and enzymes
      (e.g., iNOS). Furthermore, PARP-1 has been shown to act as a coactivator of NF
      kappaB- and other transcription factors implicated in stress/inflammation, as AP
      1, Oct-1, SP-1, HIF, and Stat-1. To further substantiate this hypothesis, we
      tested the biomolecular effects of PARP-1 inhibitors DPQ and PJ-34 on human
      glioblastoma cells, induced to a proinflammatory state with lipopolysaccharide
      and Interferon-gamma. PARP-1 expression was evaluated by laser scanning confocal
      microscopy immunofluorescence (LSM); nitrite production, LDH release and cell
      viability were also determined. LSM of A-172, SNB-19 and CAS-1 cells demonstrated
      that DPQ and PJ-34 downregulate PARP-1 expression; they also cause a decrease of
      LDH release and nitrite production, while increasing cell viability. Similar
      effects were caused in all three cell lines by N-mono-methyl-arginine, a well
      known iNOS inhibitor, and by L-carnosine and trehalose, two antioxidant
      molecules. These results demonstrate that, similar to other well characterized
      drugs, DPQ and PJ-34 reduce cell inflammation and damage that follow PARP-1
      overexpression, while they increase cell survival: this suggests their potential
      exploitation in clinical Medicine.

PMID- 23011207
TI  - A phylogenetic analysis of the L1 family of neural cell adhesion molecules.
AB  - L1-type genes form one of several distinct gene families that encode adhesive
      proteins, which are predominantly expressed in developing and mature metazoan
      nervous systems. These proteins have a multitude of different important cellular
      functions in neuronal and glial cells. L1-type gene products are transmembrane
      proteins with a characteristic extracellular domain structure consisting of six
      immunoglobulin and three to five fibronectin type III protein folds. As reported
      here, L1-type proteins can be identified in most metazoan phyla with the notable
      exception of Porifera (sponges). This puts the origin of L1-type genes at a point
      in time when primitive cellular neural networks emerged, approximately 1,200 to
      1,500 million years ago. Subsequently, several independent gene duplication
      events generated multiple paralogous L1-type genes in some phyla, allowing for a
      considerable diversification of L1 structures and the emergence of new functional
      features and molecular interactions. One such evolutionary newer feature is the
      appearance of RGD integrin-binding motifs in some vertebrate L1 family members.

PMID- 23011208
TI  - Effects of selenium and topiramate on cytosolic Ca(2+) influx and oxidative
      stress in neuronal PC12 cells.
AB  - It has been widely suggested that selenium (Se) deficiency play an important role
      in the pathophysiology of epilepsy. It has been reported that Se provides
      protection against the neuronal damage in patients and animals with epilepsy by
      restoring the antioxidant defense mechanism. The neuroprotective effects of
      topiramate (TPM) have been reported in several studies but the putative mechanism
      of action remains elusive. We investigated effects of Se and TPM in neuronal PC12
      cell by evaluating Ca(2+) mobilization, lipid peroxidation and antioxidant
      levels. PC12 cells were divided into eight groups namely control, TPM, Se,
      H(2)O(2), TPM + H(2)O(2), Se + H(2)O(2), Se + TPM and Se + TPM + H(2)O(2). The
      toxic doses and times of H(2)O(2), TPM and Se were determined by cell viability
      assay which is used to evaluate cell viability. Cells were incubated with 0.01 mM
      TPM for 5 h and 500 nM Se for 10 h. Then, the cells were exposed to 0.1 mM
      H(2)O(2) for 10 h before analysis. The cells in all groups except control, TPM
      and Se were exposed to H(2)O(2) for 15 min before analysis. Cytosolic Ca(2+)
      release and lipid peroxidation levels were higher in H(2)O(2) group than in
      control, Se and TPM combination groups although their levels were decreased by
      incubation of Se and TPM combination. However, there is no difference on Ca(2+)
      release in TPM group. Glutathione peroxidase activity, reduced glutathione and
      vitamin C levels in the cells were lower in H(2)O(2) group than in control, Se
      and TPM groups although their values were higher in the cells incubated with Se
      and TPM groups than in H(2)O(2) groups. In conclusion, these results indicate
      that Se induced protective effects on oxidative stress in PC12 cells by
      modulating cytosolic Ca(2+) influx and antioxidant levels. TPM modulated also
      lipid peroxidation and glutathione and vitamin C concentrations in the cell
      system.

PMID- 23011209
TI  - Curcumin rescues aging-related loss of hippocampal synapse input specificity of
      long term potentiation in mice.
AB  - Curcumin has neuroprotective effect and could enhance memory. However, the
      mechanisms underlying the protection of curcumin on aging-related memory decline
      are not well understood. In this study, high frequency stimulation (HFS)-induced
      long term potentiation (LTP) was evaluated by a cellular model of memory
      formation. A two-input stimulation paradigm was used to record the potentiation
      as well as synapse input specificity. The data suggested that an N-Methyl-D
      aspartate receptors (NMDAR) -dependent LTP was inducible in adult hippocampal
      slices with a characteristic of synapse input specificity. It also indicated that
      aging resulted in a reduction in LTP but more importantly a loss of synaptic
      input specificity. The reason behind the above conclusions is that LTP induction
      is more dependent on the calcium channel. This is due to a switch of the
      dependence of LTP induction to voltage-dependent calcium channel (VDCC) compared
      to NMDA receptors. Curcumin administration recovers input specificity by re
      establishing NMDA receptor dependence of induction. In addition, curcumin
      administration ameliorated aging-related increase of brain thiobarbituric acid
      reactive substances and elevated aging-related decrease of glutathione in
      hippocampus. It is then concluded that curcumin modulates hippocampal redox
      status and restores aging-related loss of synapse input specificity of HFS
      induced LTP by switching VDCC calcium source into NMDA receptor-dependent one.

PMID- 23011210
TI  - The delayed effects of irreversible electroporation ablation on nerves.
AB  - OBJECTIVE: To evaluate the delayed effects of irreversible electroporation (IRE)
      ablation on nerves. METHODS: The study was approved by the institutional animal
      care and use committee. CT-guided IRE-ablation (electric field per distance,
      1,500 V/cm; pulse length, 70 MUs; number of pulses, 90) of 6 sciatic nerves was
      performed in 6 pigs that were euthanized 2 months after ablation. The sciatic
      nerves were harvested immediately after euthanasia for histopathological
      evaluation. Sections from selected specimens were stained with haematoxylin and
      eosin (H&E), Masson's trichrome (MT) method for collagen, and
      immunohistochemistry was performed for S100 and neurofilaments (markers for
      Schwann cells and axons, respectively). RESULTS: All nerves showed a preserved
      endoneural architecture and presence of numerous small calibre axons associated
      with Schwann cell hyperplasia, consistent with axonal regeneration. A fibrous
      scar was observed in the adjacent muscle tissue, confirming ablation at the site
      examined. CONCLUSION: After IRE-ablation of nerves, the preservation of the
      architecture of the endoneurium and the proliferation of Schwann cells may enable
      axonal regeneration as demonstrated after 2 months in this study.

PMID- 23011211
TI  - Post-embolisation susceptibility changes in giant meningiomas: multiparametric
      histogram analysis using non-contrast-enhanced susceptibility-weighted PRESTO,
      diffusion-weighted and perfusion-weighted imaging.
AB  - PURPOSE: To investigate imaging characteristics of post-embolised meningioma and
      to determine if SW imaging can delineate tumour ischaemia. MATERIALS AND METHODS:
      Sixteen patients were studied before and after preoperative embolisation therapy
      (8 histopathologically determined with ischaemia, 8 with non-ischaemia). In each
      patient, a slice-wise ROI for the entire tumour was established, and histogram
      variables (mean, SD, minimum, maximum, histogram width, mode, and peak height) of
      SW, ADC, CBV, CBF, MTT, and TTP maps were compared between ischaemic and non
      ischaemic groups. Changes in SW histogram were correlated with histopathological
      characteristics. RESULTS: Signal intensity on the SW map tended to decrease in
      the ischaemic group and partially increased in the non-ischaemic group. A similar
      trend was observed on the ADC map. The PW histogram showed an MTT increase in
      ischaemic group; however, CBV did not show significant changes between ischaemic
      and non-ischaemic groups. Microhaemorrhage was slightly correlated with Deltapeak
      height in the SW histogram. CONCLUSION: Post-embolisation changes of intrinsic T2
      weighted MR contrasts on SW map are most likely associated with alterations in
      deoxyhaemoglobin levels and arterial blood flow.

PMID- 23011212
TI  - Ascending aorta dilatation in patients with bicuspid aortic valve stenosis: a
      prospective CMR study.
AB  - BACKGROUND: The aim of this study was to evaluate the natural progression of
      aortic dilatation and its association with aortic valve stenosis (AoS) in
      patients with bicuspid aortic valve (BAV). METHODS: Prospective study of aorta
      dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR).
      Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and
      diastolic function and mass were assessed at baseline and at 3-year follow-up.
      RESULTS: Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17
      male; mean age: 31 +/- 8 years) completed the study. Aortic diameters
      significantly increased at the aortic annulus, sinus of Valsalva and tubular
      ascending aorta levels (P < 0.050). The number of patients with dilated tubular
      ascending aortas increased from 32 % to 43 %. No significant increase in sino
      tubular junction diameter was observed. Aortic peak velocity, ejection fraction
      and myocardial mass significantly increased while the early/late filling ratio
      significantly decreased at follow-up (P < 0.050). The progression rate of the
      ascending aorta diameter correlated weakly with the aortic peak velocity at
      baseline (R (2) = 0.16, P = 0.040). CONCLUSION: BAV patients with AoS showed a
      progressive increase of aortic diameters with maximal expression at the level of
      the tubular ascending aorta. The progression of aortic dilatation correlated
      weakly with the severity of AoS.

PMID- 23011213
TI  - How to design the optimal self-expandable oesophageal metallic stents: 22 years
      of experience in 645 patients with malignant strictures.
AB  - OBJECTIVES: To evaluate the clinical efficacy and safety of self-expandable
      metallic stent (SEMS) placement for malignant oesophageal strictures and their
      relationship with stent designs. METHODS: Seven generations of SEMS were used to
      treat 645 consecutive patients with oesophageal strictures. Logistic regression
      models were constructed to identify predictive factors associated with
      complications. RESULTS: Stent placement was technically successful in 641 of 645
      patients (99.4%). The clinical success rate was 95.5%. There were 260 (40.3%)
      complications after stent placement. Due to complications, 68 stents were
      removed; 66 of 68 stents (97.1%) were removed successfully. Stainless steel (SS)
      stents (odds ratio [OR] 4.18; 95% confidence interval [CI] 2.10, 8.32) and
      radiation therapy (RT) before stent placement (OR 4.23; CI 2.02, 8.83) were
      significantly associated with severe pain. Flared ends (OR 9.63; CI 3.38, 27.43),
      stricture length <6 cm (OR 2.01; CI 1.13, 3.60), and a stent diameter <18 mm (OR
      3.00; CI 1.32, 6.84) were predictive factors of stent migration. Polyurethane
      membranes were associated with more frequent tumour ingrowth than
      polytetrafluoroethylene (PTFE) membranes (P = 0.002). CONCLUSIONS: Despite the
      relatively high complication rate, retrievable self-expandable PTFE-covered
      nitinol stents equipped with a head and a tail appeared to be an effective
      treatment for malignant oesophageal strictures.

PMID- 23011215
TI  - Negative affect shares genetic and environmental influences with symptoms of
      childhood internalizing and externalizing disorders.
AB  - The co-occurrence of internalizing and externalizing disorders suggests that they
      may have common underlying vulnerability factors. Research has shown that
      negative affect is moderately positively correlated with both internalizing and
      externalizing disorders in children. The present study is the first to provide an
      examination of negative affect in relation to a wide spectrum of childhood
      internalizing and externalizing problems using a biometric model. This study
      extends prior findings of more narrowly focused associations by using a factor
      approach including multiple disorders. The sample for this study included
      families of 691 same-sex 7- to 13-year old twin pairs. A multifactorial
      independent pathway model was used to examine the genetic and environmental
      influences underlying the covariation of parent-reported negative affect,
      internalizing symptoms, and externalizing symptoms. Results of the current study
      suggest that negative affect shares genetic and environmental influences with
      both internalizing and externalizing disorders in childhood. These common
      influences may partially explain their comorbidity. Understanding that negative
      affect is at least one contributor to the covariation among these disorders may
      highlight avenues for early risk assessment, intervention, and perhaps
      prevention.

PMID- 23011214
TI  - Early negative affect predicts anxiety, not autism, in preschool boys with
      fragile X syndrome.
AB  - Children with fragile X syndrome (FXS) face high risk for anxiety disorders, yet
      no studies have explored FXS as a high-risk sample for investigating early
      manifestations of anxiety outcomes. Negative affect is one of the most salient
      predictors of problem behaviors and has been associated with both anxiety and
      autistic outcomes in clinical and non-clinical pediatric samples. In light of the
      high comorbidity between autism and anxiety within FXS, the present study
      investigates the relationship between longitudinal trajectories of negative
      affect (between 8 and 71 months) and severity of anxiety and autistic outcomes in
      young males with FXS (n = 25). Multilevel models indicated associations between
      elevated anxiety and higher fear and sadness, lower soothability, and steeper
      longitudinal increases in approach. Autistic outcomes were unrelated to negative
      affect. These findings suggest early negative affect differentially predicts
      anxiety, not autistic symptoms, within FXS. Future research is warranted to
      determine the specificity of the relationship between negative affect and
      anxiety, as well as to explore potential moderators. Characterizing the
      relationship between early negative affect and anxiety within FXS may inform
      etiology and treatment considerations specific to children with FXS, as well as
      lend insight into precursors of anxiety disorders in other clinical groups and
      community samples.

PMID- 23011216
TI  - Genetic and environmental transmission of body mass index fluctuation.
AB  - This study sought to determine the relationship between body mass index (BMI)
      fluctuation and cardiovascular disease phenotypes, diabetes, and depression and
      the role of genetic and environmental factors in individual differences in BMI
      fluctuation using the extended twin-family model (ETFM). This study included
      14,763 twins and their relatives. Health and Lifestyle Questionnaires were
      obtained from 28,492 individuals from the Virginia 30,000 dataset including
      twins, parents, siblings, spouses, and children of twins. Self-report
      cardiovascular disease, diabetes, and depression data were available. From self
      reported height and weight, BMI fluctuation was calculated as the difference
      between highest and lowest BMI after age 18, for individuals 18-80 years.
      Logistic regression analyses were used to determine the relationship between BMI
      fluctuation and disease status. The ETFM was used to estimate the significance
      and contribution of genetic and environmental factors, cultural transmission, and
      assortative mating components to BMI fluctuation, while controlling for age. We
      tested sex differences in additive and dominant genetic effects, parental, non
      parental, twin, and unique environmental effects. BMI fluctuation was highly
      associated with disease status, independent of BMI. Genetic effects accounted for
      ~34 % of variance in BMI fluctuation in males and ~43 % of variance in females.
      The majority of the variance was accounted for by environmental factors, about a
      third of which were shared among twins. Assortative mating, and cultural
      transmission accounted for only a small proportion of variance in this phenotype.
      Since there are substantial health risks associated with BMI fluctuation and
      environmental components of BMI fluctuation account for over 60 % of variance in
      males and over 50 % of variance in females, environmental risk factors may be
      appropriate targets to reduce BMI fluctuation.

PMID- 23011217
TI  - [Epidemiology of occupational skin cancer due to UV-irradiation].
AB  - Skin cancer induced by occupational UV-irradiation is not an official
      occupational disease number in the appendix of the German ordinance on
      occupational diseases (Berufskrankheitenverordnung (BKV) but can be recognized as
      a "virtually" occupational disease according to S 9 (2) of the 7th book of the
      German Social Code (SGB VII). Epidemiological studies have demonstrated a
      positive, statistically significant and relevant association between occupational
      UV-irradiation and the risk of squamous cell carcinoma (SCC) and actinic
      keratoses (AK). Outdoor workers have on average a 100% higher risk to develop SCC
      compared to the general population. Therefore, the prerequisites for a new
      occupational disease are fulfilled and SCC and AK should be reported as an
      occupational disease if an additional 40% occupationally-related UV-irradiation
      is documented and the clinical criteria are typical for work- related skin
      cancer. Epidemiologic evidence also indicates a significant association between
      work-related UV-irradiation and basal cell carcinoma (BCC) risk: however the
      results are less consistent and the association is weaker than with SCC. There is
      an urgent need for further studies in outdoor workers on BCC and lentigo maligna
      melanoma.

PMID- 23011218
TI  - Rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to
      heteroaryl alpha-ketoesters for synthesis of heteroaromatic alpha-hydroxy esters.
AB  - The first example of catalytic asymmetric 1,2-addition of arylboronic acids to
      heteroaryl alpha-ketoesters has been developed for the highly efficient and
      enantioselective synthesis of quaternary carbon-containing heteroaromatic alpha
      hydroxy esters. The reaction works well with a variety of alpha-ketoesters
      including 3-indoleglyoxylates, 3-benzofuranglyoxylates and 3
      benzothiopheneglyoxylates under very mild conditions, affording the corresponding
      products in moderate to good yields with high enantiomeric excesses (up to 97%).

PMID- 23011219
TI  - Clinical and anatomical correlates of gait dysfunction in Alzheimer's disease.
AB  - We conducted a cross-sectional study to investigate the clinical and anatomical
      correlates of gait dysfunction in advanced Alzheimer's disease (AD). A
      comprehensive clinical protocol that included cognitive, functional, behavioral,
      and motor variables was administered to patients with probable AD (n = 100),
      possible AD (n = 17), and AD with cerebrovascular disease (AD + CVD) (n = 27).
      Gait dysfunction was evaluated with the Rating Scale for Gait Evaluation in
      Cognitive Deterioration and magnetic resonance imaging was analyzed in 94
      patients (volumetry study) and 78 patients (diffusion tensor imaging study).
      Univariate correlations, multivariate regression, and statistical parametric
      mapping analyses were conducted in the total sample and in the subsample of
      patients with probable AD. Mean age was 82.5 (SD 6.3, range 56 to 98), 83.3% were
      female patients, and 95.1% displayed moderate to severe dementia. Parkinsonism,
      patient setting (nursing home), dementia severity, apathy, and (worse) cognitive
      performance significantly predicted gait dysfunction in the total sample (p <
      0.05, R(2) = 0.58), whereas parkinsonism, patient setting, and limb weakness due
      to non-AD conditions predicted gait dysfunction in probable AD (p < 0.05, R(2) =
      0.57). Gait dysfunction was related to atrophy in the motor cortex, the middle
      cingulate, the anterior insula, the right caudate (total sample only), and the
      anterior lobe of the cerebellum (p < 0.01, corrected). Significant correlations
      were also observed between gait dysfunction and damage in several white matter
      locations (p < 0.001, uncorrected). The present results are congruent with a
      model of multi-system gray matter degeneration, with progressive damage to
      critical regions (i.e., motor cortex, cingulate, insula, and cerebellum)
      producing gait dysfunction and, eventually, gait loss in AD.

PMID- 23011220
TI  - Prediction of amyloid-beta pathology in amnestic mild cognitive impairment with
      neuropsychological tests.
AB  - Assessment of disease biomarkers, particularly the in vivo assessment of amyloid
      beta (Abeta) burden with positron emission tomography (PET), is gradually
      becoming central to the diagnosis of mild cognitive impairment (MCI) due to
      Alzheimer's disease (AD). However, the incorporation of biomarker evidence to the
      diagnostic process is currently restricted mainly to research settings. The
      identification of memory measures that are associated with Abeta is of clinical
      relevance as this may enhance the confidence in making a diagnosis of MCI due to
      AD in clinical settings. Forty one persons with amnestic MCI underwent Abeta
      imaging with (18)F-Florbetaben PET, magnetic resonance imaging, and a
      comprehensive neuropsychological assessment. All measures of episodic memory were
      significantly correlated with Abeta burden, but regression analyses revealed a
      strong and selective association between story recall and Abeta over and beyond
      the effects of age, education, global cognition, hippocampal volume, or other
      memory tests. Analyses of sensitivity and specificity of memory measures to
      detect high versus low Abeta scans suggested that word-list recall performed
      better when high sensitivity was preferred, whereas story recall performed better
      when high specificity was preferred. In conclusion, a measure of story recall may
      increase the confidence in making a diagnosis of MCI due to AD in clinical
      settings.

PMID- 23011221
TI  - Respectful re-use.

PMID- 23011222
TI  - Bringing the genomic landscape of small-cell lung cancer into focus.

PMID- 23011223
TI  - Genomic landscape of liver cancer.

PMID- 23011224
TI  - Tissue specificity of genetic regulation of gene expression.

PMID- 23011230
TI  - Facile carbon-sulfur bond cleavage in diarylsulfonium ylides: a catalytic sulfur
      to-silicon group transfer.
AB  - An unusual cleavage of the non-ylidic carbon-sulfur bond of a sulfonium ylide is
      reported. The reaction can be catalysed by a variety of palladium(II) complexes
      under mild conditions. Preliminary results show that coordination of the ylide to
      the metal center results in significant structural changes.

PMID- 23011231
TI  - Abdominal actinomycosis masquerading as an omental tumor in a 12-year-old female.
AB  - We herein report a case of abdominal actinomycosis in a 12-year-old girl in whom
      an omental primary tumor was suspected before surgery. The patient began to
      experience intermittent lower left abdominal pain. Abdominal computed tomography
      (CT) scans were inconclusive at this time, but 6 months later, CT and magnetic
      resonance imaging (MRI) examinations showed a 7-cm, tumor-like lesion in the left
      abdominal cavity; malignancy could not be ruled out. The tumor, which originated
      in the omentum and adhered strongly to the left abdominal wall, was resected
      along with approximately 90 % of the omentum, the peritoneum in contact with the
      mass, and the posterior layer of the rectus abdominal sheath, under suspicion of
      a malignant tumor. However, omental actinomycosis was the final pathological
      diagnosis. The patient's antibiotic treatment was changed to a penicillin-series
      oral antibiotic to prevent recurrence of the actinomycosis. The patient was
      discharged from our hospital 16 days after the first surgery, but she developed
      three episodes of ileus; the first two required surgery. The patient has had no
      further recurrences of actinomycosis or postoperative ileus 20 months after
      discharge.

PMID- 23011233
TI  - Risk factors for refractory febrile neutropenia in urological chemotherapy.
AB  - During chemotherapy, patients are more susceptible to infectious complications as
      a result of bone marrow suppression, leading to neutropenia. The purpose of this
      study is to investigate risk factors for refractory febrile neutropenia (FN)
      during urological chemotherapy. Our method for suppressing FN is to use
      granulocyte colony-stimulating factor and prevent upper respiratory infection by
      masking and gargling. We studied 47 episodes of FN in 39 patients that occurred
      during urological chemotherapy for urothelial cancer, testicular cancer, and
      prostate cancer. Among our cases, there were 5 patients with refractory FN; we
      set risk factors for refractory FN and performed statistical analyses. The
      average age of the 39 patients was 60.6 years (range, 18-80 years). In 47 FN
      episodes, the chemotherapy regimen before the occurrence of FN included 15 (31.9
      %) MVAC (methotrexate, vinblastine, adriamycin, cisplatin) for urothelial cancer,
      5 (10.6 %) DE (docetaxel, estramustin) for prostate cancer, and 3 (6.4 %) TIP
      (paclitaxel, ifosfamide, cisplatin) for testicular cancer. The antibiotics used
      to treat FN included 17 (36.3 %) meropenem and 23 (49.0 %) cefepime, and the
      average duration of antibiotics was 4.4 days (range, 1-12). We investigated risk
      factors for refractory FN and showed a significant relationship between
      refractory FN and indwelling urinary catheter or smaller Multinational
      Association for Supportive Care in Cancer score by multivariate analysis. A
      future prospective study is needed for further evaluation for risk factors and
      establishing treatment protocols and guidelines for FN.

PMID- 23011232
TI  - A case of acute hepatitis B related to previous gynecological surgery in Japan.
AB  - A 41-year-old woman became ill with acute hepatitis B after gynecological surgery
      performed by a surgeon who was hepatitis B surface antigen positive. The surgeon
      was positive for hepatitis B e antigen, and HBV DNA concentrations in the serum,
      saliva, and sweat of the surgeon were very high. HBV genotype and partial HBV DNA
      sequences from the HBV-infected surgeon were identical to those in the HBV
      infected patient. Extensive research by the committee including infection control
      and prevention specialists judged the source of infection to be a surgeon
      infected with HBV. Transmission of HBV from a healthcare worker to patients who
      are not immune to HBV can actually happen. This case report illustrates the
      importance of a stringent policy of a nationwide HBV universal vaccination
      program.

PMID- 23011234
TI  - Improved pharmacological profile of the lipophilic antitumor dichloro-(N-dodecyl)
      propanediamine-platinum(II) complex after incorporation into pegylated liposomes.
AB  - Liposome encapsulation of platinum (Pt) drugs has emerged as a promising strategy
      to overcome their toxicity and cellular Pt resistance. The aim of the present
      work was to examine the impact of liposome encapsulation of a novel antitumor
      lipophilic Pt complex, dichloro-(N-dodecyl)-propanediamine-platinum(II) complex
      (DDPP), on its pharmacological profile as an antitumor agent. Biological assays
      included acute toxicity and histopathological evaluations, pharmacokinetics, and
      growth inhibition of B16-F1 tumor cells in C57Bl/6 mice. Comparison was made with
      cisplatin and free DDPP dissolved in castor oil. DDPP encapsulated in pegylated
      liposomes showed reduced acute toxicity in mice following intraperitoneal
      administration, compared with the free complex. Free DDPP at 5 mg Pt/kg induced
      histopathological alterations in the liver, in contrast to liposomal DDPP and
      cisplatin. Interestingly, the marked loss of body weight following the treatment
      of mice with cisplatin was not observed after liposomal DDPP at the same Pt dose.
      Liposomal DDPP was found to inhibit tumor growth significantly, when administered
      at 5 mg Pt/kg/day for 3 days, similar to cisplatin, but in contrast to the free
      complex. Pharmacokinetic studies after intraperitoneal and intravenous
      administrations at 5 mg Pt/kg indicated greater and more prolonged Pt levels in
      the plasma, liver, spleen, and kidneys from liposomal DDPP, compared with free
      DDPP or cisplatin. The tumor concentration of Pt increased after liposomal DDPP
      over the 24-h period, whereas it decreased after cisplatin. In conclusion, the
      encapsulation of DDPP in pegylated liposomes reduced the drug toxicity and
      enhanced its antitumoral activity in mice, as a result of improved drug
      pharmacokinetics.

PMID- 23011235
TI  - Midline brain-in-brain malformation associated with bilateral perirolandic
      cortical abnormalities: an image review of this rare disorder.
AB  - A midline brain-in-brain malformation was recently reported, but appropriate
      classification of this malformation remains uncertain. We describe a child with a
      complex brain malformation that was not restricted to the midline structures,
      enlarging the neuroanatomical spectrum of this pseudotumoral midline dysplasia
      associated with corpus callosum dysgenesis, azygos anterior cerebral artery,
      absent septum pellucidum and bilateral perirolandic cortical abnormalities. The
      spectrum of fusion of the cerebral hemispheres and associated brain hemispherical
      abnormalities is not completely understood. Our data are in line with previous
      arguments that this malformation could be an additional variant in the spectrum
      of holoprosencephaly.

PMID- 23011237
TI  - Gastric cancer trends in epidemiology.

PMID- 23011236
TI  - Essential tremor is a neurodegenerative disease.
AB  - There are many lines of evidence supporting the idea that essential tremor is
      more than simply a monosymptomatic disorder and that all the clinical
      manifestations of this frequent disorder are sustained by a neurodegenerative
      process. The most important lines of evidence in favor of a neurodegenerative
      nature of essential tremor are: the anatomic and neuroimaging data demonstrating
      a pathologic process involving the cerebellum and/or brainstem; the progression
      of symptom severity with disease duration; and the lack of spontaneous remission
      of this condition. All of this evidence is supported by recent studies that are
      summarized in this review.

PMID- 23011238
TI  - Gastric adenocarcinoma trends in the central region of Rio Grande do Sul
      (Southern Brazil): what has changed in 25 years?
AB  - CONTEXT: Gastric cancer is the fourth most common malignancy in the world. Its
      incidence varies greatly by geographic region. The highest rate is in Eastern
      Asia, mainly in Japan and China. In Brazil, gastric cancer is the third most
      common cancer in males and the fifth most common cancer in females. Rio Grande do
      Sul state, in Southern Brazil, has similar figures. The main histological type of
      gastric cancer is adenocarcinoma. OBJECTIVE: To assess the trends of this cancer
      over 25 years in a reference center in central Rio Grande do Sul. METHODS: We
      reviewed the records of upper gastrointestinal endoscopies performed at the
      University Hospital of Santa Maria, RS, between 1986 and 2010. We evaluated the
      incidence, age and gender distribution, anatomical subsite and histological
      subtype of gastric cancer throughout this 25-year period. RESULTS: We identified
      histologically confirmed primary gastric adenocarcinoma in 335 (1.6%) of the
      20,521 patients who underwent upper gastrointestinal endoscopy during the study
      period. The mean age of patients was 62.4 (+/- 13.0) years, and 67.8% were male
      (a male: female ratio of 2.0:1). Cardia cancer accounted for 14.3% of the cases,
      and non-cardia cancer accounted for 85.7%. According to Lauren's classification,
      48.1% were intestinal subtype and 40.9% were diffuse subtype. There were no
      differences in mean age or gender distribution by anatomical location or
      histological subtype. There was also no difference in the proportions of
      histological subtypes by anatomical location. Over the 25-year period, there was
      no change in the anatomical distribution of tumors, but there was a significant
      decrease in the intestinal subtype and a steady increase in the diffuse subtype
      (P = 0.02). The subset of 39 patients (11.6%) who presented at < 45 years of age
      was more likely to be female and to have tumors of the diffuse subtype than was
      the total series of patients. CONCLUSIONS: Over this 25-year period, there were
      no significant trends in age, gender distribution, or the proportions of cardia
      and non-cardia gastric adenocarcinomas in this series of patients from Southern
      Brazil. There was a significant decrease in the intestinal subtype and a steady
      increase in the diffuse subtype of this malignancy. In patients under 45 years
      old, gastric cancer was more frequent in women, and the diffuse subtype
      predominated.

PMID- 23011239
TI  - Trend of mortality rates for gastric cancer in Brazil and regions in the period
      of 30 years (1980-2009).
AB  - CONTEXT: The most recent global estimate revealed the presence of about one
      million new cases of stomach cancer for the year 2008, setting itself as the
      fourth most common cause of cancer. OBJECTIVE: The present study aims to assess
      the trend of mortality from stomach cancer in Brazil according to regions between
      1980 and 2009. METHODS: Data on deaths from stomach cancer were obtained from the
      Mortality Information System, and the demographic data, from the Brazilian
      Institute of Geography and Statistics. The rates of mortality were standardized
      by age according to world population. The trend curves were calculated for
      Brazilian regions by sex. The technique used was polynomial regression and
      joinpoint. RESULTS: The tendency for males and females is similar in all regions,
      although the magnitude is higher among men in all places. Regions Midwest, South,
      Southeast tended to decline, while the Northern region showed no significant
      trend, and the Northeast tended to increase. CONCLUSION: It is therefore a need
      to evaluate public health policies for gastric cancer aimed at the demographic
      transition (change of urbanization and lifestyle) that is occurring throughout
      the country.

PMID- 23011240
TI  - Liver transplantation and expanded Milan criteria: does it really work?
AB  - CONTEXT: Orthotopic liver transplantation is an excellent treatment approach for
      hepatocellular carcinoma in well-selected candidates. Nowadays some institutions
      tend to Expand the Milan Criteria including tumor with more than 5 cm and also
      associate with multiple tumors none larger than 3 cm in order to benefit more
      patients with the orthotopic liver transplantation. METHODS: The data collected
      were based on the online database PubMED. The key words applied on the search
      were "expanded Milan criteria" limited to the period from 2000 to 2009. We
      excluded 19 papers due to: irrelevance of the subject, lack of information and
      incompatibility of the language (English only). We compiled patient survival and
      tumor recurrence free rate from 1 to 5-years in patients with hepatocellular
      carcinoma submitted to orthotopic liver transplantation according to expanded the
      Milan criteria from different centers. RESULTS: Review compiled data from 23
      articles. Fourteen different criteria were found and they are also described in
      detail, however the University of California - San Francisco was the most studied
      one among them. CONCLUSION: Expanded the Milan criteria is a useful attempt for
      widening the preexistent protocol for patients with hepatocellular carcinoma in
      waiting-list for orthotopic liver transplantation. However there is no
      significant difference in patient survival rate and tumor recurrence free rate
      from those patients that followed the Milan criteria.

PMID- 23011241
TI  - Weight loss during cirrhosis is related to the etiology of liver disease.
AB  - CONTEXT: Malnutrition is widely described in patients waiting for liver
      transplantation (LTx). However, risk factors associated with weight loss during
      liver disease have not yet been well studied. OBJECTIVES: The aim of this study
      was to assess weight loss and its risk factors during liver disease and up to the
      first appointment after transplantation. Patients who underwent LTx were
      retrospectively assessed for weight loss during liver disease while on the
      waiting list for LTx. The usual weight of the patients before disease and their
      weight on the first outpatient appointment after transplant were considered.
      Demographic, socioeconomic, lifestyle and clinical variables were collected to
      assess risk factors using a linear regression analysis. We retrospectively
      evaluated 163 patients undergoing LTx between 1997 and 2008. RESULTS: Patients
      lost in average 7.7 +/- 12.4 kg while ill. Variables independently associated
      with weight loss by multiple linear regression analyses were as follows: former
      smoker (P = 0.03), greater body mass index (P<0.01), overweight before liver
      disease (P = 0.02) and indication for LTx (P = 0.01). Among these indications,
      patients with alcoholic cirrhosis had lost significantly more weight (P<0.01),
      and those with hepatitis C virus (P = 0.01) and autoimmune hepatitis (P = 0.02)
      had lost significantly less weight. CONCLUSIONS: Patients experienced weight loss
      during liver disease independent of age, sex, schooling and income; however, the
      etiology of liver disease was related to weight loss.

PMID- 23011242
TI  - Autoantibodies in relatives of celiac disease patients: a follow-up of 6-10
      years.
AB  - CONTEXT: Autoimmune diseases are 3 to 10 times more frequently in patients with
      celiac disease and their relatives than in the general population. OBJECTIVE: To
      investigate a broad spectrum of autoantibodies in celiac disease relatives from
      Southern Brazil, in a serological follow-up of 6-10 years, aiming to associate
      with other autoimmune diseases, degree of parentage, demographic and clinical
      data. METHODS: Serum samples of 233 relatives were analyzed in two different
      phases: n = 186 in phase I (1997-2000) and n = 138 (being 91 = follow-up group
      and 47 = newly tested) in phase II (2006-2007). As controls, 100 unrelated
      individuals were evaluated. Autoantibodies to smooth muscle, mitochondrial, liver
      kidney microssome, parietal cell and thyroid microssome were tested by indirect
      immunofluorescence. RESULTS: A significant increase of autoantibodies, in both
      phases, was observed in the relatives when compared to the non-relatives (P =
      0.0064), specifically to anti-thyroid microssome and anti-parietal cell. In both
      phases, the female/male proportion of autoantibodies was of 4:1 to 3:1 (P<0.041).
      The frequency of autoantibodies amongst 1st and 2nd degree relatives was 11.8%
      and 9.68% in phase I and 4% and 6.67% in phase II. CONCLUSION: Celiac disease
      relatives presented other autoantibodies and serological screening is a useful
      instrument for identifying autoimmune diseases along the years.

PMID- 23011243
TI  - Celiac disease in first degree relatives of celiac children.
AB  - CONTEXT: The first degree relatives of celiac patients represent a high risk
      group for the development of this disorder, so their screening may be crucial in
      the prevention of long-term complications. OBJECTIVE: In order to determine the
      prevalence of celiac disease in a group of first degree relatives of children
      with proven gluten intolerance, we conducted a prospective study that consisted
      in the screening of celiac disease, using a capillary immunoassay rapid test that
      allows a qualitative detection of IgA antibody to human recombinant tissue
      transglutaminase (IgA-TTG). METHODS: When the screening test was positive
      subjects were advised to proceed with further investigation. The screening test
      was performed in 268 first degree relatives (143 mothers, 89 fathers, 36
      siblings) corresponding to 163 children with celiac disease. RESULTS: Screening
      test was positive in 12 relatives (4.5%), of which 1 refused to continue the
      investigation. In the remaining 11 relatives celiac disease was diagnosed in 7
      cases (2.6%, 5 mothers, 2 fathers) who had a median age of 39 years (27-56
      years), mild gastrointestinal symptoms, high titre of IgA-TTG and histology
      abnormalities confirming the diagnosis. All these patients are currently on a
      gluten-free diet. CONCLUSION: The prevalence of celiac disease among first degree
      relatives (2.6%) was 5 times higher than that in the general population. Although
      the recommendations for screening asymptomatic high risk groups, such as first
      degree relatives, are not unanimous the early diagnosis is crucial in preventing
      complications, including nutritional deficiency and cancer.

PMID- 23011244
TI  - Alimentary factors in the development of gastric intestinal metaplasia in
      functional dyspeptic patients.
AB  - CONTEXT: Intestinal metaplasia of the stomach is a lesion in which metaplasia of
      gastric epithelial cells occurs for an intestinal phenotype. Gastric intestinal
      metaplasia is a lesion associated with an increase in the risk of gastric
      carcinoma development. Epidemiologic studies indicate a relation between dietary
      habits and stomach cancer development, some habits increasing the risk for it,
      and others have a protective effect, suggesting that antioxidants, such as
      vitamins A, C, and E, decrease the risk of this type of cancer. The relationship
      of these alimentary factors and intestinal metaplasia is unknown. METHODS: It is
      a case-control, observational study in which 320 patients with functional
      dyspepsia, divided in two groups, were assessed. The case I group (individuals
      with intestinal metaplasia) had their dietary pattern compared to that of the
      control group, constituted of individuals similar to those in the case group but
      without intestinal metaplasia, through a food frequency questionnaire. RESULTS:
      The analysis of the dietary pattern of functional dyspeptic patients with
      intestinal metaplasia, and its comparison with those without intestinal
      metaplasia, showed a higher frequency of canned and smoked foods consumption in
      the first group and, on the other hand, a higher consumption of fruits and
      vegetables in patients without intestinal metaplasia. No effect of salt
      consumption was detected. CONCLUSIONS: The results obtained in this study suggest
      changes in the diet, with a decrease in the consumption of smoked and canned
      foods, and an increase in the consumption of fruits and vegetables, can lead to a
      diminution of gastric intestinal metaplasia cases.

PMID- 23011245
TI  - Salivary parameters and teeth erosions in patients with gastroesophageal reflux
      disease.
AB  - CONTEXT: In the gastroesophageal reflux disease (GERD), a highly prevalent
      digestive disorder, gastric content may return to the esophagus and reach the
      mouth, thus leading to a small number of carious lesions and high incidence of
      dental erosion. Since saliva plays a major role in oral homeostasis, evaluating
      salivary parameters is necessary in attempting to explain such outcome.
      OBJECTIVES: This study aimed at analyzing salivary parameters (salivary flow, pH
      and buffering capacity), bacterial count, caries index and dental erosion in
      patients with GERD. MATERIALS: Sixty patients were studied, and of these, 30 had
      GERD (group 1), and 30 were controls (group 2). Gastroesophageal reflux disease
      diagnosis confirmation was achieved by means of endoscopy, manometry and pH
      metric esophageal monitoring. The above mentioned salivary parameters were
      evaluated in patients from groups 1 and 2. RESULTS: The number of erosions in
      patients with GERD (group 1) was larger than in controls (P<0.001). The number of
      carious teeth was smaller in group 1 than in group 2 (P<0.001). Salivary flow
      (non-stimulated and stimulated) and pH did not show differences between the 2
      groups (P = 0.49; P = 0.80 and P = 0.85, respectively). Salivary buffering
      capacity in patients with GERD showed lower values in controls (P = 0.018). The
      number of bacteria (Lactobacilli and Streptococci) was smaller in patients with
      gastroesophageal reflux disease than in controls (P = 0.0067 and P = 0.0017,
      respectively). CONCLUSION: It was concluded that the large number of erosions
      must be a result of GERD patients reduced salivary buffering capacity. The
      reduced number of caries of patients in group 1 can be explained by the low
      prevalence of bacteria (Lactobacilli and Streptococci), observed in the saliva of
      patients with chronic reflux.

PMID- 23011246
TI  - Assessing the extent of colon lengthening due to splenic flexure mobilization
      techniques: a cadaver study.
AB  - CONTEXT: Failure of a colorectal anastomosis represents a life-threatening
      complication of colorectal surgery. Splenic flexure mobilization may contribute
      to reduce the occurrence of anastomotic complications due to technical flaws.
      There are no published reports measuring the impact of splenic flexure
      mobilization on the length of mobilized colon viable to construct a safe
      colorectal anastomosis. OBJECTIVE: The aim of the present study was to determine
      the effect of two techniques for splenic flexure mobilization on colon
      lengthening during open left-sided colon surgery using a cadaver model. DESIGN:
      Anatomical dissections for left colectomy and colorectal anastomosis at the
      sacral promontory level were conducted in 20 fresh cadavers by the same team of
      four surgeons. The effect of partial and full splenic flexure mobilization on the
      extent of mobilized left colon segment was determined. SETTING: University of Sao
      Paulo Medical School, Sao Paulo, SP, Brazil. Tertiary medical institution and
      university hospital. PARTICIPANTS: A team of four surgeons operated on 20 fresh
      cadavers. RESULTS: The length of resected left colon enabling a tension-free
      colorectal anastomosis at the level of sacral promontory achieved without
      mobilizing the splenic flexure was 46.3 (35-81) cm. After partial mobilization of
      the splenic flexure, an additionally mobilized colon segment measuring 10.7 (2
      30) cm was obtained. After full mobilization of the distal transverse colon, a
      mean 28.3 (10-65) cm segment was achieved. CONCLUSION: Splenic flexure
      mobilization techniques are associated to effective left colon lengthening for
      colorectal anastomosis. This result may contribute to decision-making during
      rectal surgery and low colorectal and coloanal anastomosis.

PMID- 23011247
TI  - Minilaparoscopic fundoplication: technical adaptations and initial experience.
AB  - CONTEXT: Gastroesophageal reflux disease (GERD) is a highly prevalent disease.
      Treatment is divided into lifestyle modifications, medical and surgical
      treatment. Surgical laparoscopy is the gold standard treatment. In the last
      decade, there were an extensive research on procedures, less aggressive than
      laparoscopy and with better esthetic results. Minilaparoscopy is "reemerging" as
      a safe, effective and with excellent cosmetic results in selected patients
      treated for gastroesophageal reflux disease. We present a serie of 27 patients
      treated for GERD by minilaparoscopic laparoscopy. MATERIAL: Between October 2009
      July 2011 a total of 27 patients underwent fundoplication by minilaparoscopy. It
      is used one 10mm trocar, a telescope of 30 degrees and four 3 mm trocars at
      regular positions. Regular surgical steps are done with no modifications. Cardiac
      tape, suture needles, and eventually extracting bag, gauze, are placed and taken
      out through the umbilical port. With these technical adjustments, we can perform
      the procedure safely and effectively, similarly to standard laparoscopic
      technique. RESULTS: Of the 27 patients, 22 were female and 5 male. The average
      body mass index was 25.5 kg/m2. Hiatal hernias were small (<3 cm) in 24 patients.
      Mean operative time was 60 minutes. In all cases the hiatoplasty was performed
      with simple or 'x' stitches of 2.0 Ethibond. There was no need for conversion to
      standard laparoscopy or open surgery. The length of hospital stay was less than
      or equal to 24 hours in all patients. In this series of patients there were no
      postoperative complications. We did not observe any complication of the surgical
      wound. There were no evidence of recurrence of symptoms or endoscopic changes.
      CONCLUSION: Hiatoplasty associated with fundoplication using minilaparoscopic
      instruments is safe, feasible and effective. If compared to other "new access",
      has a spectacular esthetic results. Can be done with only minor technical
      adjustments, for any experienced laparoscopic surgeon, and is perfectly adaptable
      to our financial reality.

PMID- 23011248
TI  - Percutaneous endoscopic gastrostomy for nutritional palliation of upper
      esophageal cancer unsuitable for esophageal stenting.
AB  - CONTEXT: Esophageal cancer is often diagnosed at an advanced stage and has a poor
      prognosis. Most patients with advanced esophageal cancer have significant
      dysphagia that contributes to weight loss and malnutrition. Esophageal stenting
      is a widespread palliation approach, but unsuitable for cancers near the upper
      esophageal sphincter, were stents are poorly tolerated. Generally, guidelines do
      not support endoscopic gastrostomy in this clinical setting, but it may be the
      best option for nutritional support. OBJECTIVE: Retrospective evaluation of
      patients with dysphagia caused advanced esophageal cancer, no expectation of
      resuming oral intake and with percutaneous endoscopic gastrostomy for comfort
      palliative nutrition. METHOD: We selected adult patients with unresecable
      esophageal cancer histological confirmed, in whom stenting was impossible due to
      proximal location, and chemotherapy or radiotherapy were palliative, using
      gastrostomy for enteral nutrition. Clinical and nutritional data were evaluated,
      including success of gastrostomy, procedure complications and survival after
      percutaneous endoscopic gastrostomy, and evolution of body mass index, albumin,
      transferrin and cholesterol. RESULTS: Seventeen males with stage III or IV
      squamous cell carcinoma fulfilled the inclusion criteria. Mean age was 60.9
      years. Most of the patients had toxic habits. All underwent palliative
      chemotherapy or radiotherapy. Gastrostomy was successfully performed in all, but
      nine required prior dilatation. Most had the gastrostomy within 2 months after
      diagnosis. There was a buried bumper syndrome treated with tube replacement and
      four minor complications. There were no cases of implantation metastases or
      procedure related mortality. Two patients were lost and 12 died. Mean survival of
      deceased patients was 5.9 months. Three patients are alive 6, 14 and 17 months
      after the gastrostomy procedure, still increasing the mean survival. Mean body
      mass index and laboratory parameters were roughly stable 1 and 3 months after the
      gastrostomy procedure. CONCLUSIONS: In patients with advanced upper esophageal
      cancer where only palliative treatment is possible, nutritional support is easily
      achieved with percutaneous endoscopic gastrostomy, allowing patients to be at
      homes, surviving a significant period of time. Percutaneous endoscopic
      gastrostomy feeding should be considered as standard definitive nutritional
      palliation in patients with upper esophageal cancer, unsuitable for esophageal
      stenting.

PMID- 23011249
TI  - Relationship between serum transforming growth factor beta1 and liver collagen
      content in rats treated with carbon tetrachloride.
AB  - CONTEXT: Transforming Growth Factor beta1 (TGFbeta1) plays a fundamental role in
      fibrogenesis, although its importance as a biomarker of liver disease is still
      matter of debate. OBJECTIVE: Quantify serum TGFbeta1 and its association to liver
      collagen content in rats exposed to Carbon Tetrachloride (CCl4). METHODS: Rats
      were submitted to a fibrosis model using CCl4 and sacrificed after 6, 10, 12 and
      16 weeks of treatment. Serum levels of TGFbeta1 were measured by ELISA and
      collagen content was defined by morphometric analysis. RESULTS: Serum levels of
      TGFbeta1 increased between 6 and 10 weeks, whereas collagen density increased
      between 12 and 16 weeks. A negative correlation was observed between liver
      collagen deposition and serum levels of TGFbeta1 (r = -0. 48; P<0. 05).
      CONCLUSION: Serum levels of TGFbeta1 were inversely proportional to collagen
      intensity in cirrhotic livers of rats exposed to CCl4, thus suggesting a limited
      use as biomarker in advanced liver disease.

PMID- 23011251
TI  - Brief report: comparability of DSM-IV and DSM-5 ASD research samples.
AB  - Diagnostic and Statistical Manual (DSM-5) criteria for ASD have been criticized
      for being too restrictive, especially for more cognitively-able individuals. It
      is unclear, however, if high-functioning individuals deemed eligible for research
      via standardized diagnostic assessments would meet DSM-5 criteria. This study
      investigated the impact of DSM-5 on the diagnostic status of 498 high-functioning
      participants with ASD research diagnoses. The percent of participants satisfying
      all DSM-5-requirements varied significantly with reliance on data from the Autism
      Diagnostic Observation Schedule (ADOS; 33 %) versus Autism Diagnostic Interview
      Revised (ADI-R; 83 %), highlighting the impact of diagnostic methodology on
      ability to document DSM-5 symptoms. Utilizing combined ADOS/ADI-R data, 93 % of
      participants met DSM-5 criteria, which suggests likely continuity between DSM-IV
      and DSM-5 research samples characterized with these instruments in combination.

PMID- 23011252
TI  - Executive and visuo-motor function in adolescents and adults with autism spectrum
      disorder.
AB  - This study broadly examines executive (EF) and visuo-motor function in 30
      adolescent and adult individuals with high-functioning autism spectrum disorder
      (ASD) in comparison to 28 controls matched for age, gender, and IQ. ASD
      individuals showed impaired spatial working memory, whereas planning, cognitive
      flexibility, and inhibition were spared. Pure movement execution during visuo
      motor information processing also was intact. In contrast, execution time of
      reading, naming, and of visuo-motor information processing tasks including a
      choice component was increased in the ASD group. Results of this study are in
      line with previous studies reporting only minimal EF difficulties in older
      individuals with ASD when assessed by computerized tasks. The finding of impaired
      visuo-motor information processing should be accounted for in further
      neuropsychological studies in ASD.

PMID- 23011255
TI  - Influence of endourological devices on 3D reconstruction image quality using the
      Uro Dyna-CT.
AB  - PURPOSE: The urological Dyna-CT (Uro Dyna-CT) was established in clinical use for
      classical imaging as well as for interventional surgery. To evaluate whether
      irradiation artefacts may occur during interventional surgery, we analysed the
      impact of different instruments on 3D reconstruction in the Uro Dyna-CT.
      MATERIALS AND METHODS: Ten different endourological instruments [ureterorenoscope
      (URS)-fibrescope, percutaneous nephrolithotomy (PCNL) working sheath] and
      accessory equipments such as ureteral catheter, guide wires and stents (DJ, MJ)
      were introduced in a porcine renal pelvis either retrograde via the ureter or
      transparenchymally. Subsequently, digital fluoroscopy, standard X-ray and an Uro
      Dyna-CT were performed. Three colleagues evaluated the image quality independent
      from each other. RESULTS: There were basically no limitations regarding image
      quality in digital fluoroscopy and standard X-ray. In the Uro Dyna-CT, only with
      the URS fiberscope and the PCNL working sheath, small artefacts and irradiations
      were detected, whereas ureteric catheter with and without wire, as well as the
      hydrophilic guide wire, showed no artefacts at all. The remaining material
      demonstrated minimal artefacts, which did not affect the image quality.
      CONCLUSIONS: The Uro Dyna-CT can be used for all interventional endourological
      procedures using the common armamentarium and instruments without significant
      limitation of image quality. There are only minor limitations according a PCNL
      working sheath and the rigid URS. These instruments should be removed out of the
      examination field before performing the computed tomography and be replaced
      afterwards by using a safety wire.

PMID- 23011253
TI  - I don't want to be the one saying 'we should just let him die': intrapersonal
      tensions experienced by surrogate decision makers in the ICU.
AB  - BACKGROUND: Although numerous studies have addressed external factors associated
      with difficulty in surrogate decision making, intrapersonal sources of tension
      are an important element of decision making that have received little attention.
      OBJECTIVE: To characterize key intrapersonal tensions experienced by surrogate
      decision makers in the intensive care unit (ICU), and explore associated coping
      strategies. DESIGN: Qualitative interview study. PARTICIPANTS: Thirty surrogates
      from five ICUs at two hospitals in Pittsburgh, Pennsylvania, who were actively
      involved in making life-sustaining treatment decisions for a critically ill loved
      one. APPROACH: We conducted in-depth, semi-structured interviews with surrogates,
      focused on intrapersonal tensions, role challenges, and coping strategies. We
      analyzed transcripts using constant comparative methods. KEY RESULTS: Surrogates
      experience significant emotional conflict between the desire to act in accordance
      with their loved one's values and 1) not wanting to feel responsible for a loved
      one's death, 2) a desire to pursue any chance of recovery, and 3) the need to
      preserve family well-being. Associated coping strategies included 1) recalling
      previous discussions with a loved one, 2) sharing decisions with family members,
      3) delaying or deferring decision making, 4) spiritual/religious practices, and
      5) story-telling. CONCLUSIONS: Surrogates' struggle to reconcile personal and
      family emotional needs with their loved ones' wishes, and utilize common coping
      strategies to combat intrapersonal tensions. These data suggest reasons
      surrogates may struggle to follow a strict substituted judgment standard. They
      also suggest ways clinicians may improve decision making, including attending to
      surrogates' emotions, facilitating family decision making, and eliciting
      potential emotional conflicts and spiritual needs.

PMID- 23011256
TI  - Disease-free survival as a surrogate for overall survival in upper tract
      urothelial carcinoma.
AB  - OBJECTIVES: The primary endpoint in trials of perioperative systemic therapy for
      urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint
      could significantly speed the translation of advances into practice. We
      hypothesized that disease-free survival (DFS) could be a surrogate endpoint for
      OS in upper tract urothelial carcinoma (UTUC) patients treated with radical
      nephroureterectomy (RNU). PATIENTS AND METHODS: The study included 2,492 patients
      treated with RNU with curative intent for UTUC. RESULTS: 2/3-year DFS estimates
      were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between
      2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were
      similar when analyzed in subgroups stratified by pathological stages, lymph node
      status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55
      0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61-0.68) for 3-year DFS/5-year
      OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent
      variable for predicting OS was 11.5 (95 % CI 9.1-14.4), indicating a strong
      relationship between DFS and OS. CONCLUSIONS: In patients treated with RNU for
      UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant
      chemotherapy. While significant differences in DFS, assessed at 2 and 3 years,
      are highly likely to persist in OS at 5 years, marginal DFS advantages may not
      translate into OS benefit. External validation is necessary before accepting DFS
      as an appropriate surrogate endpoint for clinical trials investigating advanced
      UTUC patients.

PMID- 23011257
TI  - TVT versus TOT, 2-year prospective randomized study.
AB  - PURPOSE: To evaluate in a comprehensive way TVT in comparison with TOT, the
      results of a single-center RCT are presented. Many studies addressed efficacy and
      safety of TVT and TOT. METHODS: Women included were adults having predominant SUI
      with positive stress test. They were randomized to get either TVT (Gynecare((r)))
      or TOT (Aris((r))). All women were seen 1 week, 3, 6, 12, 18, and 24 months.
      RESULTS: Seventy-one women completed 2-year follow-up. Median age was 47 (range
      33-60 years). Mean +/- SD BMI in TVT group was 34 +/- 5 while in TOT group was 32
      +/- 5 kg/m(2). POP of any degree was seen in 50 % (35 women). At 1 year, pad test
      negative women were 31 and 29 for TVT and TOT, respectively. At 2 years, figures
      became 28 in TVT group and 27 in TOT. At 1 year, UDI 6 and IIQ 7 decreased by
      78.5 and 81 % for TVT and by 69 % and 75 % for TOT group. At 2 year, comparable
      percentages were 73 and 79 % for TVT and 69 and 82 % for TOT. Fifteen unique
      patients had adverse events, 10 of them had TOT. CONCLUSIONS: Both tapes have
      similar efficacy, regarding cure of incontinence. TVT is more effective, albeit
      insignificantly, than TOT at 2 years. However, serious adverse events were more
      frequent with TVT, yet TOT has more unique adverse events.

PMID- 23011258
TI  - MTHFR C677T polymorphism among three Mendelian populations: a study from North
      India.

PMID- 23011259
TI  - Lack of association of NOS3 and ACE gene polymorphisms with coronary artery
      disease in Southern Tunisia.

PMID- 23011260
TI  - Hebbian mechanisms help explain development of multisensory integration in the
      superior colliculus: a neural network model.
AB  - The superior colliculus (SC) integrates relevant sensory information (visual,
      auditory, somatosensory) from several cortical and subcortical structures, to
      program orientation responses to external events. However, this capacity is not
      present at birth, and it is acquired only through interactions with cross-modal
      events during maturation. Mathematical models provide a quantitative framework,
      valuable in helping to clarify the specific neural mechanisms underlying the
      maturation of the multisensory integration in the SC. We extended a neural
      network model of the adult SC (Cuppini et al., Front Integr Neurosci 4:1-15,
      2010) to describe the development of this phenomenon starting from an immature
      state, based on known or suspected anatomy and physiology, in which: (1) AES
      afferents are present but weak, (2) Responses are driven from non-AES afferents,
      and (3) The visual inputs have a marginal spatial tuning. Sensory experience was
      modeled by repeatedly presenting modality-specific and cross-modal stimuli.
      Synapses in the network were modified by simple Hebbian learning rules. As a
      consequence of this exposure, (1) Receptive fields shrink and come into spatial
      register, and (2) SC neurons gained the adult characteristic integrative
      properties: enhancement, depression, and inverse effectiveness. Importantly, the
      unique architecture of the model guided the development so that integration
      became dependent on the relationship between the cortical input and the SC.
      Manipulations of the statistics of the experience during the development changed
      the integrative profiles of the neurons, and results matched well with the
      results of physiological studies.

PMID- 23011261
TI  - [Epidemiology, anatomy, biomechanics and imaging of acromioclavicular joint
      injuries].
AB  - Current techniques of acromioclavicular (AC) joint repair primarily focus on the
      reconstruction of the coracoclavicular (CC) ligaments. However, it is not clear
      if this approach is sufficient to restore vertical as well as horizontal AC joint
      stability and kinematics. This review focuses on the epidemiology of AC joint
      injuries and the coincidence of intra-articular pathologies. Furthermore, the
      clinically relevant anatomy and the pathomechanism of AC joint instability are
      described. The biomechanical characteristics of current procedures as they have
      been revealed by in vitro investigations are summarized. As a basic result,
      neither selective repair of the CC ligaments nor selective repair of the AC
      ligaments could be shown to restore both vertical and horizontal joint stability.
      Similar to the intact ligaments CC repair primarily provides vertical joint
      stability while AC repair is able to restore horizontal stability. In conclusion
      a biomechanically effective treatment of AC joint separation should analyze the
      individual instability pattern in the first step. Therefore, the radiological
      standard according to Rockwood should be supplemented by specific stress x-rays
      for quantification of dynamic horizontal AC joint instability. In the second step
      an adequate surgical treatment considering CC and AC stabilization should be
      performed meeting the individual patient requirements.

PMID- 23011262
TI  - [Prophylaxis of thromboembolic events following hip and knee replacement:
      dabigatran, rivaroxaban or apixaban in comparison to enoxaparin].

PMID- 23011263
TI  - Hot extruded carbon nanotube reinforced aluminum matrix composite materials.
AB  - Carbon nanotube (CNT) reinforced aluminum (Al) matrix composite materials were
      successfully fabricated by mechanical ball milling followed by powder hot
      extrusion processes. Microstructural analysis revealed that the CNTs were well
      dispersed at the boundaries and were aligned with the extrusion direction in the
      composites obtained. Although only a small quantity of CNTs were added to the
      composite (1 vol%), the Vickers hardness and the tensile strength were
      significantly enhanced, with an up to three-fold increase relative to that of
      pure Al. From the fractography of the extruded Al-CNT composite, several shapes
      were observed in the fracture surface, and this unique morphology is discussed
      based on the strengthening mechanism. The damage in the CNTs was investigated
      with Raman spectroscopy. However, the Al-CNT composite materials were not only
      strengthened by the addition of CNTs but also enhanced by several synergistic
      effects. The nanoindentation stress-strain curve was successfully constructed by
      setting the effective zero-load and zero-displacement points and was compared
      with the tensile stress-strain curve. The yield strengths of the Al-CNT
      composites from the nanoindentation and tensile tests were compared and
      discussed. We believe that the yield strength can be predicted using a simple
      nanoindentation stress/strain curve and that this method will be useful for
      materials that are difficult to machine, such as complex ceramics.

PMID- 23011264
TI  - Low-flow mediated constriction is endothelium-dependent: effects of exercise
      training after radial artery catheterization.
AB  - BACKGROUND: Radial artery catheterization is associated with endothelial
      denudation and impaired vasodilator function, while postcatheterization exercise
      training may enhance artery function. The impact of catheterization and
      subsequent exercise training on low-flow mediated vasoconstriction (L-FMC) has
      not previously been studied. The aim of this study was to examine whether radial
      artery L-FMC is impaired by catheterization and consequent endothelial
      denudation. A further aim was to examine the effect of local handgrip exercise
      training on radial artery L-FMC and flow-mediated dilation (FMD) after
      transradial catheterization. METHODS AND RESULTS: Thirty-two subjects undergoing
      transradial catheterization underwent assessment of L-FMC and FMD in the
      catheterized and contralateral radial artery before, and the day after,
      catheterization. A further 18 patients were recruited and randomly assigned to
      either a 6-week handgrip exercise training program (N=9) or a nonexercise control
      period (N=9). L-FMC was attenuated 1 day postcatheterization in the catheterized
      arm (-2.07+/-0.84 to 0.35+/-0.83), but unchanged in the noncatheterized arm (
      0.93+/-0.86 to -0.90+/-0.92; P<0.05). In the training study, both FMD and L-FMC
      of the catheterized arm were preserved in the exercise group 7 weeks after
      catheterization (FMD-pre, 6.84+/-0.79; FMD-post, 6.85+/-1.16; L-FMC-pre, -2.14+/
      1.42; L-FMC-post, -3.58+/-1.04%), but reduced in the control group (FMD-pre,
      8.27+/-1.52; FMD-post, 4.66+/-0.70; P=0.06; L-FMC-pre, -3.26+/-1.19; L-FMC-post, 
      1.34+/-1.27%; P<0.05). CONCLUSIONS: Catheterization, and associated endothelial
      denudation, decreases L-FMC in the radial artery, suggesting that it is
      endothelium-dependent. Moreover, we demonstrate for the first time that exercise
      training has beneficial impacts on radial artery vasodilator and constrictor
      function.

PMID- 23011265
TI  - Optical coherence tomography findings in lesions after sirolimus-eluting stent
      implantation with peri-stent contrast staining.
AB  - BACKGROUND: We have sometimes noted abnormal angiographic coronary dilatation,
      <50% of the reference vessel, at the site of sirolimus-eluting stent
      implantation, suggesting contrast staining outside the stent struts and named
      this finding peri-stent contrast staining (PSS). Little was known about optical
      coherence tomography findings of lesions with PSS. METHODS AND RESULTS: Between
      May 2008 and March 2010, we performed optical coherence tomography for 90 in
      stent restenosis lesions after sirolimus-eluting stent implantation. We found PSS
      in 20 of the 90 lesions by coronary angiography. The differences in optical
      coherence tomography findings, including incomplete stent apposition, multiple
      interstrut hollows (MIH), strut coverage, and thrombus, were compared between
      lesions with PSS and those without PSS. PSS is defined as contrast staining
      outside the stent contour extending to >20% of the stent diameter measured by
      quantitative coronary angiography. MIH is defined as multiple hollows (the
      maximum depth >0.5 mm) existing between and outside well-apposed stent struts.
      Both incomplete stent apposition (60.0% versus 10%; P<0.001) and MIH (85.0%
      versus 25.7%; P<0.001) were frequently observed in lesions with PSS than in
      lesions without PSS. Among the 20 lesions with PSS, there was only 1 lesion in
      which we found neither MIH nor incomplete stent apposition, but only minor
      dissection. Uncovered struts (11.6% versus 3.9%; P=0.001), malapposed struts
      (2.0% versus 0.0%; P<0.001), and red thrombus (35% versus 10%; P=0.012) were
      frequently observed in lesions with PSS than in lesions without PSS. CONCLUSIONS:
      PSS might be closely associated with 2 different optical coherence tomography
      findings, MIH and incomplete stent apposition, in lesions after sirolimus-eluting
      stent implantation.

PMID- 23011266
TI  - Incidence and clinical impact of stent fracture after everolimus-eluting stent
      implantation.
AB  - BACKGROUND: Stent fracture (SF) after drug-eluting stent implantation has
      recently become an important concern because of its potential association with in
      stent restenosis and stent thrombosis. However, the incidence and clinical impact
      of SF after everolimus-eluting stent implantation remain unclear. METHODS AND
      RESULTS: A total of 1035 patients with 1339 lesions undergoing everolimus-eluting
      stent implantation and follow-up angiography 6 to 9 months after index procedure
      were analyzed. SF was defined as complete or partial separation of the stent, as
      assessed by plain fluoroscopy or intravascular ultrasound during follow-up. We
      assessed the rates of SF and major adverse cardiac events, defined as cardiac
      death, myocardial infarction, stent thrombosis, and clinically driven target
      lesion revascularization within 9 months. SF was observed in 39 of 1339 lesions
      (2.9%) and in 39 of 1035 patients (3.8%). Ostial stent location and lesions with
      hinge motion, tortuosity, or calcification were independent predictors of SF. The
      rate of myocardial infarction and target lesion revascularization were
      significantly higher in the SF group than in the non-SF group (5.1% versus 0.4%;
      P=0.018 and 25.6% versus 2.0%; P<0.001, respectively). Stent thrombosis was more
      frequently observed in the SF group than in the non-SF group (5.1% versus 0.4%;
      P=0.018). Major adverse cardiac events within 9 months were significantly higher
      in the SF group than in the non-SF group (25.6% versus 2.3%; P<0.001).
      CONCLUSIONS: SF after everolimus-eluting stent implantation occurs in 2.9% of
      lesions and is associated with higher rate of major adverse cardiac events,
      driven by higher target lesion revascularization and stent thrombosis.

PMID- 23011267
TI  - Involvement of the ventral tegmental area in a rodent model of post-traumatic
      stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is an anxiety disorder of considerable
      prevalence in individuals who have experienced a traumatic event. Studies of the
      neural substrate of this disorder have focused on the role of areas such as the
      hippocampus, the amygdala and the medial prefrontal cortex. We show that the
      ventral tegmental area (VTA), which directly modulates these areas, is part of
      this circuitry. Using a rat model of PTSD, we show that a brief but intense foot
      shock followed by three brief reminders can cause long-term behavioral changes as
      shown by anxiety-like, nociception, and touch-sensitivity tests. We show that an
      intraperitoneal injection of a dopamine (DA) antagonist or a bilateral
      inactivation of the VTA administered immediately before the traumatic event
      decrease the occurrence or intensity of these behavioral changes. Furthermore, we
      show that there is a significant decrease of baseline VTA dopaminergic but not
      GABAergic cell firing rates 2 weeks after trauma. Our data suggest that VTA DA
      neurons undergo long-term physiological changes after trauma and that this brain
      area is a crucial part of the circuits involved in PTSD symptomatology.

PMID- 23011269
TI  - An evaluation of medication review reports  across different settings.
AB  - BACKGROUND: There is a growing body of evidence which supports that a pharmacist
      conducted medication review increases the health outcomes for patients. A
      pharmacist integrated into a primary care medical centre may offer many potential
      advantages in conducting medication reviews in this setting however research
      describing this is presently limited. OBJECTIVE: To compare medication review
      reports conducted by pharmacists practicing externally to a medical centre to
      those medication review reports conducted by an integrated practice pharmacist.
      The secondary objective was to compare medication review reports conducted by
      pharmacists in the patient's home to those conducted in the medical centre.
      SETTING: A primary care medical centre, Brisbane, Australia. METHOD: A
      retrospective analysis of pharmacist conducted medication reviews prior to and
      after the integration of a pharmacist into a medical centre. MAIN OUTCOME
      MEASURES: Types of drug related problems identified by the Pharma cists,
      recommended intervention for drug related problems made by the pharmacist, and
      the extent of implementation of pharmacist recommendations by the general
      practitioner. RESULTS: The primary drug related problem reported in the practice
      pharmacist phase was Additional therapy required as compared to Precautions in
      the external pharmacist phase. The practice pharmacist most frequently
      recommended to add drug with Additional monitoring recommended most often in the
      external pharmacists. During the practice pharmacist phase 71 % of
      recommendations were implemented and was significantly higher than the external
      pharmacist phase with 53 % of recommendations implemented (p < 0.0001). Two of
      the 23 drug related problem domains differed significantly when comparing
      medication reviews conducted in the patient's home to those conducted in the
      medical centre.

PMID- 23011268
TI  - Disrupted-in-schizophrenia-1 Gln31Leu polymorphism results in social anhedonia
      associated with monoaminergic imbalance and reduction of CREB and beta-arrestin
      1,2 in the nucleus accumbens in a mouse model of depression.
AB  - Disrupted-in-schizophrenia-1 (DISC1) is associated with mental disorders,
      including major depression. We previously showed that DISC1-Q31L mutant mice have
      depression-like behaviors and can therefore be used to study neurobiological
      mechanisms of depression and antidepressant (AD) medication action. First, we
      found reduced levels of dopamine, serotonin and norepinephrine in the nucleus
      accumbens (NAC) of DISC1-Q31L mutants. Next, we assessed social-conditioned place
      preference as a reward-dependent task and the capacity of distinct ADs to correct
      impaired social behavior in DISC1-Q31L mice. Bupropion, but not fluoxetine or
      desipramine, was able to correct deficient social facilitation, social reward,
      and social novelty in DISC1-Q31L mutants, whereas all three ADs were able to
      improve social motivation and behavioral despair in DISC1-Q31L mutants.
      Furthermore, we sought to correlate social anhedonia with molecular and cellular
      features including dendritic spine density, beta-arrestin-1,2, and cAMP-response
      element-binding protein (CREB) in the NAC as biomarkers related to depression and
      the DISC1 pathway. DISC1-Q31L mutants showed reduced levels of beta-arrestin-1,2,
      CREB, and spine density in the NAC, further supporting the construct validity of
      the genetic model. Bupropion induced the greatest effect on CREB in DISC1-Q31L
      mutants, whereas all studied ADs corrected the reduced levels of beta-arrestin
      1,2 and modestly ameliorated deficient spine density in this brain region.
      Overall, we find neurobiological changes accompanying social anhedonia in the NAC
      of DISC1-Q31L mutant mice, consistent with a role for DISC1 in regulating social
      reward as an endophenotype of depression.

PMID- 23011272
TI  - Directional stack exchange along oriented oligothiophene stacks.
AB  - Directional growth of pi-basic oligothiophene stacks on solid substrates is
      achieved by self-organizing, surface-initiated disulfide exchange polymerization.
      Successful addition of co-axial pi-acidic stacks by templated hydrazone exchange
      provides general access to multicomponent architectures of unique complexity.

PMID- 23011270
TI  - Predictors of response of patients with solid tumors to granulocyte colony
      stimulating factor.
AB  - BACKGROUND: Granulocyte colony-stimulating factor administration is an important
      component of supportive therapy in chemotherapy-induced leukopenia. Although
      patient response to granulocyte colony-stimulating factor administration is known
      to vary, the factors responsible for poor response have not been identified.
      OBJECTIVE: To identify the predictors of the responses of patients with solid
      tumors to granulocyte colony-stimulating factor. SETTING: A 600-bed university
      hospital offering secondary and tertiary care in Japan. METHODS: This
      retrospective cohort study examined the response of 181 patients with solid
      tumors who were administered prophylactic granulocyte colony-stimulating factor
      for the first time after they developed severe grade 3/4 leukopenia (white blood
      cell count <2,000 * 10(-9)/L) because of adjuvant or neoadjuvant chemotherapy.
      The granulocyte colony-stimulating factor response was defined as the length of
      the leukocyte recovery period, which was assessed as the period within which the
      normal white blood cell count (white blood cell count >3,000 * 10(-9)/L) is
      reached after the first dosage of granulocyte colony-stimulating factor. After
      classification of the patients as either poor or normal granulocyte colony
      stimulating factor responders according to the confidence interval of the
      recovery period, their characteristics were compared. MAIN OUTCOME MEASURE: The
      time for recovery to normal white blood cell count was 2-7 days (90 % confidence
      interval), and the cutoff value for differentiating poor responders (n = 14) from
      normal responders (n = 167) was 8 days. Univariate analysis identified previous
      radiotherapy, number of chemotherapy courses, high granulocyte colony-stimulating
      factor dosage, and hypoalbuminemia to be significantly associated with
      granulocyte colony-stimulating factor response. Multivariate analysis identified
      undergoing four or more chemotherapy courses (odds ratio = 5.09; 95 % confidence
      interval, 1.14-22.71) and heart failure (odds ratio = 5.96; 95 % confidence
      interval, 1.09-32.57) to be significantly associated with poor granulocyte colony
      stimulating factor response. CONCLUSIONS: Undergoing four or more chemotherapy
      courses and heart failure are independent risk factors for poor response to
      granulocyte colony-stimulating factor. These findings may help prevent the
      complications of leukopenia during chemotherapy and highlight the need to develop
      better strategies for preventing and treating infectious disease in patients
      undergoing granulocyte colony-stimulating factor administration.

PMID- 23011273
TI  - Synthesis and cytotoxicity evaluation of 13-n-alkyl berberine and palmatine
      analogues as anticancer agents.
AB  - By introducing long carbon-chain alkyl groups at the C-13 position of berberine
      and palmatine, 13-n-hexyl/13-n-octyl berberine and palmatine chloride analogues
      4a-d were synthesized and examined by MTT assays for cytotoxic activity in seven
      human cancer cell lines (7701QGY, SMMC7721, HepG2, CEM, CEM/VCR, KIII, Lewis),
      yielding IC50 values of 0.02 +/- 0.01-13.58 +/- 2.84 MUM. 13-n-Octyl palmatine
      (compound 4d) gave the most potent inhibitor activity, with an IC50 of 0.02 +/-
      0.01 MUM for SMMC7721. In all cases, the 13-n-alkyl berberine and palmatine
      analogues 4a-d were more cytotoxic than berberine and palmatine. In addition,
      compounds 4a-d also exhibited more potent cytotoxicity than berberine and
      palmatine in mice with S180 sarcoma xenografted in vivo. The primary screening
      results indicated that the 13-n-hexyl/13-n-octyl berberine and palmatine
      analogues might be valuable source for new potent anticancer drug candidates.

PMID- 23011274
TI  - Benzopyranones from the endophytic fungus Hyalodendriella sp. Ponipodef12 and
      their bioactivities.
AB  - The endophytic fungus Hyalodendriella sp. Ponipodef12 was isolated from the
      hybrid 'Neva' of Populus deltoides Marsh * P. nigra L. In this study, four
      benzopyranones were isolated from the ethyl acetate extract of Hyalodendriella
      sp. Ponipodef12, and identified as palmariol B (1), 4-hydroxymellein (2),
      alternariol 9-methyl ether (3), and botrallin (4) by means of physicochemical and
      spectroscopic analysis. All the compounds were evaluated for their antibacterial,
      antifungal, antinematodal and acetylcholinesterase inhibitory activities. 4
      Hydroxymellein (2) exhibited stronger antibacterial activity than the other
      compounds. Palmariol B (1) showed stronger antimicrobial, antinematodal and
      acetylcholinesterase inhibitory activities than alternariol 9-methyl ether (3)
      which indicated that the chlorine substitution at position 2 may contribute to
      its bioactivity. The results indicate the potential of this endophytic fungus as
      a source of bioactive benzopyranones.

PMID- 23011276
TI  - Effects of yeast polysaccharide on growth and flavonoid accumulation in Fagopyrum
      tataricum sprout cultures.
AB  - The purpose of this study was to investigate the effects of yeast polysaccharide
      (YPS) on growth and flavonoid accumulation in sprout cultures of Fagopyrum
      tataricum (tartary buckwheat). Without obvious change in the appearance of the
      sprouts, the exogenous YPS notably stimulated the production of functional
      metabolites in F. tataricum sprouts, and the stimulation effect was concentration
      dependent. With 400 mg/L of YPS applied to the sprout cultures on day 6, the
      total rutin and quercentin content was effectively increased to 42.8 mg/gdw, or
      about 1.4-fold in comparison with the control of 31.2 mg/gdw. Feeding with 800
      mg/L of YPS on day 9, the sprouts biomass was increased by about 8% compared to
      the control culture (0.99 gdw/100 sprouts versus 0.92 gdw/100 sprouts). Moreover,
      the present study revealed that the accumulation of these bioactive metabolites
      resulted from the stimulation of the phenylpropanoid pathway by YPS treatment. It
      could be an effective strategy for improving the functional quality of the F.
      tataricum sprouts provided with YPS.

PMID- 23011275
TI  - Chemical composition and biological activity of extracts from Salvia bicolor
      Desf. growing in Egypt.
AB  - A petroleum ether extract (PEE) and a methanolic extract (ME) of aerial parts of
      Salvia bicolor Desf were prepared, and their chemical compositions and
      antioxidant, anti-inflammatory, analgesic and antimicrobial activities were
      evaluated. GC/MS analysis of the PEE revealed the presence of 20 compounds in the
      unsaponifiable matter, among which beta-sitosterol and beta-amyrin (constituting
      24.75% and 15.62%, respectively) were the main constituents, and 21 fatty acids,
      with linolenic acid and erucic acid being the main fatty acid constituents
      (21.65% and 16.65%, respectively). HPLC/MS analysis of the methanol extract for
      individual phenolics revealed the presence of 14 phenolic acids; protocatchuic
      acid was predominant (75.22 mg/g dry sample), followed by p-coumaric, gallic and
      synergic acids (70.27, 68.26 and 54.38 mg/g dry weight, respectively). HPLC/MS
      analysis of flavonoid contents revealed the presence of five flavonoid compounds,
      among which luteolin 7-O-glucoside and apigenin were the major constituents
      (120.25 mg/100 g dry sample and 88.48 mg/100g dry sample, respectively). The
      antioxidant activities of both extracts were evaluated using the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay, and the total antioxidant capacity was determined in
      terms of GAE (gallic acid equivalents). Anti-inflammatory and analgesic
      activities were evaluated using the rat paw edema and hot plate testing methods,
      respectively. The antimicrobial activities of both the PEE and ME were examined
      by means of the disk-diffusion method. The Salvia bicolor PEE and ME exhibited
      significant antioxidant, anti-inflammatory, and analgesic properties, in addition
      to antimicrobial effects against the selected microorganisms.

PMID- 23011277
TI  - A concise synthesis of glycolipids based on aspartic acid building blocks.
AB  - L-aspartic acid building blocks bearing galactosyl moieties were used to
      synthesise glycolipid mimetics of variable hydrocarbon chain length. The
      glycolipids were readily prepared through amide bond formation using the
      TBTU/HOBt coupling methodology. It was observed that, under these conditions,
      activation of the alpha-carboxylic acid of the intermediates led to near complete
      racemisation of the chiral centre if the reaction was carried out in the presence
      of a base such as triethylamine. The enantiomerically pure glycolipids were
      obtained after careful consideration of the synthetic sequence and by performing
      the coupling reactions in the absence of base.

PMID- 23011278
TI  - Weinreb amidation as the cornerstone of an improved synthetic route to A-ring
      modified derivatives of luotonin A.
AB  - Weinreb amidation of ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate with
      aromatic amines provides a significantly improved route to anilide-type key
      intermediates for the synthesis of the anticancer alkaloid, luotonin A, and new A
      ring-modified derivatives thereof. This method has advantages concerning overall
      yield, brevity, and versatility with regard to the aromatic amine component, even
      if the latter has less favourable nucleophilicity, solubility and/or stability
      properties. This is demonstrated by the concise synthesis of a small library of
      luotonin A analogues, including a novel thiophene isostere of the alkaloid.

PMID- 23011279
TI  - Study of the in vitro antiplasmodial, antileishmanial and antitrypanosomal
      activities of medicinal plants from Saudi Arabia.
AB  - The present study investigated the in vitro antiprotozoal activity of sixteen
      selected medicinal plants. Plant materials were extracted with methanol and
      screened in vitro against erythrocytic schizonts of Plasmodium falciparum,
      intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free
      trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5
      cells to assess selectivity. The criterion for activity was an IC50 < 10 MUg/mL
      (<5 MUg/mL for T. brucei) and a selectivity index of >=4. Antiplasmodial activity
      was found in the extracts of Prosopis juliflora and Punica granatum.
      Antileishmanial activity against L. infantum was demonstrated in Caralluma
      sinaica and Periploca aphylla. Amastigotes of T. cruzi were affected by the
      methanol extract of Albizia lebbeck pericarp, Caralluma sinaica, Periploca
      aphylla and Prosopius juliflora. Activity against T. brucei was obtained in
      Prosopis juliflora. Cytotoxicity (MRC-5 IC50 < 10 MUg/mL) and hence non-specific
      activities were observed for Conocarpus lancifolius.

PMID- 23011280
TI  - Theory of the transition from sequential to concerted electrochemical proton
      electron transfer.
AB  - A theory for the calculation of potential energy surfaces of electrochemical
      proton-coupled electron transfer is considered and parameterized on the basis of
      thermodynamic relations. The paper discusses the qualitatively different
      potential energy surfaces predicted by the theory, and their relation to the
      existence of sequential and concerted proton-electron transfer pathways. The
      concomitant activation energies for sequential and concerted PET are calculated.
      The applied overpotential may change the qualitative shape of the PES and
      therefore the mechanism of the proton-coupled electron transfer reaction.

PMID- 23011283
TI  - Boolean modeling in systems biology: an overview of methodology and applications.
AB  - Mathematical modeling of biological processes provides deep insights into complex
      cellular systems. While quantitative and continuous models such as differential
      equations have been widely used, their use is obstructed in systems wherein the
      knowledge of mechanistic details and kinetic parameters is scarce. On the other
      hand, a wealth of molecular level qualitative data on individual components and
      interactions can be obtained from the experimental literature and high-throughput
      technologies, making qualitative approaches such as Boolean network modeling
      extremely useful. In this paper, we build on our research to provide a
      methodology overview of Boolean modeling in systems biology, including Boolean
      dynamic modeling of cellular networks, attractor analysis of Boolean dynamic
      models, as well as inferring biological regulatory mechanisms from high
      throughput data using Boolean models. We finally demonstrate how Boolean models
      can be applied to perform the structural analysis of cellular networks. This
      overview aims to acquaint life science researchers with the basic steps of
      Boolean modeling and its applications in several areas of systems biology.

PMID- 23011284
TI  - Olfactory discrimination ability of South African fur seals (Arctocephalus
      pusillus) for enantiomers.
AB  - Using a food-rewarded two-choice instrumental conditioning paradigm we assessed
      the ability of South African fur seals, Arctocephalus pusillus, to discriminate
      between 12 enantiomeric odor pairs. The results demonstrate that the fur seals as
      a group were able to discriminate between the optical isomers of carvone,
      dihydrocarvone, dihydrocarveol, menthol, limonene oxide, alpha-pinene, fenchone
      (all p < 0.01), and beta-citronellol (p < 0.05), whereas they failed to
      distinguish between the (+)- and (-)-forms of limonene, isopulegol, rose oxide,
      and camphor (all p > 0.05). An analysis of odor structure-activity relationships
      suggests that a combination of molecular structural properties rather than a
      single molecular feature may be responsible for the discriminability of
      enantiomeric odor pairs. A comparison between the discrimination performance of
      the fur seals and that of other species tested previously on the same set of
      enantiomers (or subsets thereof) suggests that the olfactory discrimination
      capabilities of this marine mammal are surprisingly well developed and not
      generally inferior to that of terrestrial mammals such as human subjects and non
      human primates. Further, comparisons suggest that neither the relative nor the
      absolute size of the olfactory bulbs appear to be reliable predictors of between
      species differences in olfactory discrimination capabilities. Taken together, the
      results of the present study support the notion that the sense of smell may play
      an important and hitherto underestimated role in regulating the behavior of fur
      seals.

PMID- 23011285
TI  - Day 3 embryo transfer may have better pregnancy outcomes in younger than 35-year
      old patients with poor ovarian response.
AB  - OBJECTIVE: To explore the pregnancy outcomes of embryo transfer with D2 or D3
      embryos in patients with poor ovarian response. METHODS: The pregnancy outcomes
      of 620 patients who had poor ovarian response and underwent the first in vitro
      fertilization-embryo transfer (IVF-ET) were retrospectively analyzed. Of the 620
      cycles, all available fresh D2 embryos were used in 365 cycles (day 2 embryo
      transfer) and all available fresh D3 embryos were used in 255 cycles (day 3
      embryo transfer) without superfluous embryos for freezing. RESULTS: There was a
      significant difference in clinical pregnancy rate between day 2 (32.73 %) and day
      3 (50.83 %) embryo transfer in younger than 35-year-old patients, but no
      significant differences in implantation rate, live birth rate and spontaneous
      abortion rate (P > 0.05). There were similar pregnancy outcomes between day 2 and
      3 embryo transfer in 35-year and older patients. CONCLUSION: D3 embryo transfer
      may have better pregnancy outcomes in younger than 35-year-old patients with poor
      ovarian response.

PMID- 23011286
TI  - Changes in microbial communities associated with the sea anemone Anemonia viridis
      in a natural pH gradient.
AB  - Ocean acidification, resulting from rising atmospheric carbon dioxide
      concentrations, is a pervasive stressor that can affect many marine organisms and
      their symbionts. Studies which examine the host physiology and microbial
      communities have shown a variety of responses to the ocean acidification process.
      Recently, several studies were conducted based on field experiments, which take
      place in natural CO(2) vents, exposing the host to natural environmental
      conditions of varying pH. This study examines the sea anemone Anemonia viridis
      which is found naturally along the pH gradient in Ischia, Italy, with an aim to
      characterize whether exposure to pH impacts the holobiont. The physiological
      parameters of A. viridis (Symbiodinium density, protein, and chlorophyll a+c
      concentration) and its microbial community were monitored. Although reduction in
      pH was seen to have had an impact on composition and diversity of associated
      microbial communities, no significant changes were observed in A. viridis
      physiology, and no microbial stress indicators (i.e., pathogens, antibacterial
      activity, etc.) were detected. In light of these results, it appears that
      elevated CO(2) does not have a negative influence on A. viridis that live
      naturally in the site. This suggests that natural long-term exposure and dynamic
      diverse microbial communities may contribute to the acclimation process of the
      host in a changing pH environment.

PMID- 23011287
TI  - Complete nucleotide sequence of the large conjugative pTC2 multireplicon plasmid
      encoding the VIM-1 metallo-beta-lactamase.
AB  - OBJECTIVES: To determine the complete nucleotide sequence of the VIM-1-encoding
      plasmid pTC2, which was isolated from a Greek Providencia stuartii multiresistant
      strain. METHODS: The pTC2 plasmid was extracted and sequenced using shotgun and 3
      kb paired-end DNA libraries and a 454 sequencing approach. Following assembly
      into a unique scaffold, gaps were closed by PCR followed by Sanger DNA
      sequencing. Gene predictions and annotations were performed using the CAAT-Box
      tool and the Conserved Domain Search service. Sequence comparisons were performed
      using the Artemis Comparison Tool. RESULTS: Plasmid pTC2 (180,184 bp) was found
      to be a multireplicon plasmid (IncA/C and IncR), with a large IncA/C backbone and
      a mosaic multidrug resistance (MDR) region, in which was inserted a 13 kb IncR
      fragment. Gene annotation allowed the identification of a complete IncA/C-type
      transfer system and of several putative maintenance modules, both on the IncA/C
      backbone and on the IncR fragment. The complex MDR region contained 9 insertion
      sequences (7 IS26, 1 IS1 and 1 IS6100), 10 resistance genes and a mercury
      resistance operon integrated into unit transposons, composite transposons or
      integrons. CONCLUSIONS: The pTC2 combines a broad host range, transfer and
      maintenance capacities, plasticity of the MDR region and a wide variety of
      resistance genes, properties that may contribute to the spreading of resistance
      determinants.

PMID- 23011288
TI  - The silver cation (Ag+): antistaphylococcal activity, mode of action and
      resistance studies.
AB  - OBJECTIVES: To examine several poorly understood or contentious aspects of the
      antibacterial activity of silver (Ag(+)), including its cidality, mode of action,
      the prevalence of resistance amongst clinical staphylococcal isolates and the
      propensity for Staphylococcus aureus to develop Ag(+) resistance. METHODS: The
      effects of Ag(+) on the viability, macromolecular synthesis and membrane
      integrity of S. aureus SH1000 were assessed using established methodology. Silver
      nitrate MICs were determined for a collection of staphylococcal isolates (n =
      1006) collected from hospitals across Europe and Canada between 1997 and 2010. S.
      aureus biofilms were grown using the Calgary Biofilm Device. To examine the in
      vitro development of staphylococcal resistance to Ag(+), bacteria were subjected
      to continuous subculture in the presence of sub-MIC concentrations of Ag(+).
      RESULTS: Silver was bactericidal against S. aureus in buffered solution, but
      bacteriostatic in growth medium, and was unable to eradicate staphylococcal
      biofilms in vitro. Challenge of S. aureus with Ag(+) caused rapid loss of
      membrane integrity and inhibition of the major macromolecular synthetic pathways.
      All clinical staphylococcal isolates were susceptible to <= 16 mg/L silver
      nitrate and prolonged exposure (42 days) to Ag(+) in vitro failed to select
      resistant mutants. CONCLUSIONS: The rapid and extensive loss of membrane
      integrity observed upon challenge with Ag(+) suggests that the antibacterial
      activity results directly from damage to the bacterial membrane. The universal
      susceptibility of staphylococci to Ag(+), and failure to select for resistance to
      Ag(+), suggest that silver compounds remain a viable option for the prevention
      and treatment of topical staphylococcal infections.

PMID- 23011289
TI  - Contribution of OqxAB efflux pumps to quinolone resistance in extended-spectrum
      beta-lactamase-producing Klebsiella pneumoniae.
AB  - OBJECTIVES: The aims of this study were to analyse the presence of oqxA and oqxB
      genes in a collection of extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae strains, to determine their chromosomal and/or plasmidic
      locations and to analyse expression levels in relation to susceptibility or
      resistance to quinolones. METHODS: A collection of 114 non-repetitive isolates of
      ESBL-producing K. pneumoniae was used. K. pneumoniae ATCC 27799 and K. pneumoniae
      ATCC 700603 were also included. Detection of oqxA and oqxB genes was performed by
      PCR. Testing for chromosomal and/or plasmidic location was carried out using
      plasmid DNA and subsequent hybridization. oqxA gene expression was analysed using
      real-time RT-PCR. Transfer of the plasmid-encoded OqxAB was evaluated. RESULTS:
      The prevalence of both oqxA and oqxB detected in K. pneumoniae was high: 76% and
      75%, respectively. Hybridization assays showed that oqxA (16%) and oqxB (13%)
      were simultaneously present in locations on the chromosome and on large plasmids.
      The plasmids were transferable by transformation into K. pneumoniae. RT-PCR
      assays showed higher expression (4-fold) in strains with reduced susceptibility
      to quinolones than in susceptible strains. Interestingly, K. pneumoniae ATCC
      700603 showed an 18-fold higher expression than K. pneumoniae ATCC 27799. These
      differences were in accordance with quinolone susceptibility. CONCLUSIONS: The
      prevalence of the OqxAB efflux pump (both chromosomal and plasmid encoded) in
      ESBL-producing K. pneumoniae is high in Spain and represents a potential
      reservoir for the spread of these genes. High expression of this pump contributes
      to reduced susceptibility to quinolones in clinical isolates of ESBL-producing K.
      pneumoniae.

PMID- 23011290
TI  - The beneficial effect of high-dose mizoribine combined with cyclosporine,
      basiliximab, and corticosteroids on CMV infection in renal transplant recipients.
AB  - BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent,
      but has a less potent immunosuppressive effect up to 3 mg/kg/day MZR. Therefore,
      we investigated whether high-dose MZR, at 6 mg/kg/day, would be effective and
      safe for kidney transplant patients in conjunction with cyclosporine (CsA),
      basiliximab, and corticosteroids. METHODS: A total of 40 living related patients
      were administered MZR (6 mg/kg/day), CsA (7 mg/kg/day), prednisolone (maintenance
      dose 10 mg/day), and basiliximab (20 mg/body). A control group (n = 38) treated
      with CsA, mycophenolate mofetil (MMF, 25 mg/kg/day), basiliximab, and
      corticosteroids was also employed in this study. RESULTS: The 2-year graft
      survival rates for the MZR and MMF groups were 100 and 94.7 %, respectively. The
      rejection rate in the MZR group (25 %) was not significantly higher than that in
      the MMF group (16 %). Serum creatinine level was not significant between the two
      groups. The number of patients who developed cytomegalovirus (CMV) disease was 0
      (0 %) in the MZR group and 7 (18.4 %) in the MMF group (P < 0.05). The number of
      patients treated with ganciclovir was 3 (7.5 %) and 11 (28.9 %) (P < 0.05),
      respectively. CONCLUSIONS: The combination of high-dose MZR with CsA,
      basiliximab, and corticosteroids can establish not only satisfactory
      immunosuppression but also a low rate of CMV infection in vivo.

PMID- 23011291
TI  - Stiffness parameter beta as a predictor of the 4-year all-cause mortality of
      chronic hemodialysis patients.
AB  - BACKGROUND: There is a lack of information on stiffness parameter beta, an index
      of arterial stiffness, in hemodialysis (HD) patients. The aim of the present
      study was to investigate whether stiffness parameter beta is predictive of the
      long-term mortality of chronic HD patients. METHODS: We measured biochemical
      parameters and the stiffness parameter beta of 80 patients on maintenance HD
      therapy and followed their course for 4 years, and we enrolled 70 of these 80
      patients in the study. We divided the 70 patients into tertiles according to
      their stiffness parameter beta values, and conducted multivariate analyses to
      examine the impact of the tertiles on 4-year mortality. RESULTS: Older age and
      the presence of diabetes mellitus were found to be independently associated with
      higher stiffness parameter beta values. Fifteen patients (21.4 %) died and 16
      (22.9 %) experienced a new cardiovascular event during the follow-up period. The
      results of a Kaplan-Meier analysis revealed a significantly higher risk of all
      cause mortality in the HD patients with highest stiffness parameter beta values
      (p = 0.0106). According to the ROC curve, the cut-off level that yielded maximal
      sensitivity and specificity for predicting all-cause mortality was 10.1, and the
      sensitivity and specificity using the cut-off value were 69.2 and 70.2 %,
      respectively. CONCLUSION: The results of this study suggest that stiffness
      parameter beta is a predictor of all-cause mortality in chronic HD patients.

PMID- 23011292
TI  - Additive effects of cilnidipine and angiotensin II receptor blocker in preventing
      the progression of diabetic nephropathy in diabetic spontaneously hypertensive
      rats.
AB  - BACKGROUND: Cilnidipine (Cil) is an L/N-type calcium channel blocker (CCB) that
      is known to provide renal protection by decreasing the activity of the
      sympathetic nervous system and the renin-angiotensin system (RAS). However, very
      few studies have evaluated the renoprotective effects of Cil in hypertension
      complicated by diabetes mellitus. In this study, we compared the effects of
      cilnidipine and the L-type CCB, amlodipine (Aml), in combination with an
      angiotensin II receptor blocker (ARB) on diabetic nephropathy that developed as a
      result of inducing diabetes in hypertensive rats. METHODS: Diabetes was induced
      in 9-week-old male spontaneously hypertensive rats by intraperitoneally injecting
      them with streptozotocin (40 mg/kg twice) and the rats (8 per group) were
      randomly assigned to receive valsartan (Val), Cil + Val, Aml + Val, or vehicle
      for 8 weeks through a gastric tube. RESULTS: There were no significant
      differences in systolic blood pressure or plasma parameters between the two
      combination therapy groups. Blood pressure lowering by neither combination
      therapy significantly affected the glycemic variables. However, the increased
      glycogen levels in the kidney as a result of hyperglycemia were significantly
      suppressed in the groups that received combination therapy, and the increased
      proteinurea and glomerulosclerosis due to progression of the diabetic nephropathy
      were significantly suppressed in the Cil + Val group. In addition, a significant
      decrease in ED-1-positive cells was observed in the Cil + Val group alone.
      CONCLUSION: The results of this study suggested that the L/N-type CCB,
      cilnidipine, had additive antihypertensive and proteinuria-lowering effects when
      administered in combination with an ARB, even in type-1 diabetic rats, and that
      the L-type CCB, amlodipine, did not. Furthermore, combination therapy with
      cilnidipine and valsartan significantly reduced glycogen accumulation and ED-1
      positive cell infiltration, suggesting that cilnidipine suppressed the excessive
      increase in the activity of the sympathetic nervous system and RAS through N-type
      calcium channel blockade.

PMID- 23011293
TI  - Central hepatectomy under sequential hemihepatic control.
AB  - PURPOSE: Central hepatectomy is a complex, parenchymal-sparing procedure which
      has been associated with increased blood loss, prolonged operating time, and
      increased duration of remnant hypoxia. In this report, we compare two different
      techniques of vascular control, namely sequential hemihepatic vascular control
      (SHHVC) and selective hepatic vascular exclusion (SHVE) in central hepatectomies.
      METHODS: From January 2000 to September 2011, 36 consecutive patients underwent a
      central hepatectomy. SVHE was applied in 16 consecutive patients, and SHHVC was
      applied in 20 patients. Both groups were comparable regarding their demographics.
      RESULTS: Total operative time and morbidity rates were similar in both groups.
      Warm ischemia time was significantly longer in SVHE patients (46 min vs 28 min, p
      = 0.03). Total blood loss and number of transfusions per patient were also higher
      in the SVHE group (650 vs. 400 mL, p = 0.04 and 2.2 vs. 1.2 units, p = 0.04,
      respectively). AST values were significantly higher in SVHE on days 1 and 3
      compared to SHHVC patients (650 vs. 400, p = 0.04 and 550 vs. 250, p = 0.001,
      respectively). CONCLUSION: Sequential hemihepatic vascular control is a safe
      technique for central hepatectomies. Decreased intraoperative blood loss and
      transfusions and attenuated liver injury are the main advantages of this
      approach.

PMID- 23011294
TI  - Carbon and nitrogen stock and fluxes in coastal Atlantic Forest of southeast
      Brazil: potential impacts of climate change on biogeochemical functioning.
AB  - The Atlantic Forest is one of the most important biomes of Brazil. Originally
      covering approximately 1.5 million of km2, today this area has been reduced to
      12% of its original size. Climate changes may alter the structure and the
      functioning of this tropical forest. Here we explore how increases in temperature
      and changes in precipitation distribution could affect dynamics of carbon and
      nitrogen in coastal Atlantic Forest of the southeast region of Brazil The main
      conclusion of this article is that the coastal Atlantic Forest has high stocks of
      carbon and nitrogen above ground, and especially, below ground. An increase in
      temperature may transform these forests from important carbon sinks to carbon
      sources by increasing loss of carbon and nitrogen to the atmosphere. However,
      this conclusion should be viewed with caution because it is based on limited
      information. Therefore, more studies are urgently needed to enable us to make
      more accurate predictions.

PMID- 23011295
TI  - Biogeochemical cycling in terrestrial ecosystems of the Caatinga Biome.
AB  - The biogeochemical cycles of C, N, P and water, the impacts of land use in the
      stocks and flows of these elements and how they can affect the structure and
      functioning of Caatinga were reviewed. About half of this biome is still covered
      by native secondary vegetation. Soils are deficient in nutrients, especially N
      and P. Average concentrations of total soil P and C in the top layer (0-20 cm)
      are 196 mg kg(-1) and 9.3 g kg(-1), corresponding to C stocks around 23 Mg ha(
      1). Aboveground biomass of native vegetation varies from 30 to 50 Mg ha(-1), and
      average root biomass from 3 to 12 Mg ha(-1). Average annual productivities and
      biomass accumulation in different land use systems vary from 1 to 7 Mg ha(-1)
      year(-1). Biological atmospheric N2 fixation is estimated to vary from 3 to 11 kg
      N ha(-1) year-1 and 21 to 26 kg N ha(-1) year(-1) in mature and secondary
      Caatinga, respectively. The main processes responsible for nutrient and water
      losses are fire, soil erosion, runoff and harvest of crops and animal products.
      Projected climate changes in the future point to higher temperatures and rainfall
      decreases. In face of the high intrinsic variability, actions to increase
      sustainability should improve resilience and stability of the ecosystems. Land
      use systems based on perennial species, as opposed to annual species, may be more
      stable and resilient, thus more adequate to face future potential increases in
      climate variability. Long-term studies to investigate the potential of the native
      biodiversity or adapted exotic species to design sustainable land use systems
      should be encouraged.

PMID- 23011296
TI  - Potential impacts of climate change on biogeochemical functioning of Cerrado
      ecosystems.
AB  - The Cerrado Domain comprises one of the most diverse savannas in the world and is
      undergoing a rapid loss of habitats due to changes in fire regimes and intense
      conversion of native areas to agriculture. We reviewed data on the biogeochemical
      functioning of Cerrado ecosystems and evaluated the potential impacts of regional
      climate changes. Variation in temperature extremes and in total amount of
      rainfall and altitude throughout the Cerrado determines marked differences in the
      composition of species. Cerrado ecosystems are controlled by interactions between
      water and nutrient availability. In general, nutrient cycles (N, P and base
      cations) are very conservative, while litter, microbial and plant biomass are
      important stocks. In terms of C cycling, root systems and especially the soil
      organic matter are the most important stocks. Typical cerrado ecosystems function
      as C sinks on an annual basis, although they work as source of C to the
      atmosphere close to the end of the dry season. Fire is an important factor
      altering stocks and fluxes of C and nutrients. Predicted changes in temperature,
      amount and distribution of precipitation vary according to Cerrado sub-regions
      with more marked changes in the northeastern part of the domain. Higher
      temperatures, decreases in rainfall with increase in length of the dry season
      could shift net ecosystem exchanges from C sink to source of C and might
      intensify burning, reducing nutrient stocks. Interactions between the
      heterogeneity in the composition and abundance of biological communities
      throughout the Cerrado Domain and current and future changes in land use make it
      difficult to project the impacts of future climate scenarios at different
      temporal and spatial scales and new modeling approaches are needed.

PMID- 23011297
TI  - The southern Brazilian grassland biome: soil carbon stocks, fluxes of greenhouse
      gases and some options for mitigation.
AB  - The southern Brazilian grassland biome contains highly diverse natural ecosystems
      that have been used for centuries for grazing livestock and that also provide
      other important environmental services. Here we outline the main factors
      controlling ecosystem processes, review and discuss the available data on soil
      carbon stocks and greenhouse gases emissions from soils, and suggest
      opportunities for mitigation of climatic change. The research on carbon and
      greenhouse gases emissions in these ecosystems is recent and the results are
      still fragmented. The available data indicate that the southern Brazilian natural
      grassland ecosystems under adequate management contain important stocks of
      organic carbon in the soil, and therefore their conservation is relevant for the
      mitigation of climate change. Furthermore, these ecosystems show a great and
      rapid loss of soil organic carbon when converted to crops based on conventional
      tillage practices. However, in the already converted areas there is potential to
      mitigate greenhouse gas emissions by using cropping systems based on no soil
      tillage and cover-crops, and the effect is mainly related to the potential of
      these crop systems to accumulate soil organic carbon in the soil at rates that
      surpass the increased soil nitrous oxide emissions. Further modelling with these
      results associated with geographic information systems could generate regional
      estimates of carbon balance.

PMID- 23011298
TI  - Nitrogen mass balance in the Brazilian Amazon: an update.
AB  - The main purpose of this study is to perform a nitrogen budget survey for the
      entire Brazilian Amazon region. The main inputs of nitrogen to the region are
      biological nitrogen fixation occurring in tropical forests (7.7 Tg.yr(-1)), and
      biological nitrogen fixation in agricultural lands mainly due to the cultivation
      of a large area with soybean, which is an important nitrogen-fixing crop (1.68
      Tg.yr(-1)). The input due to the use of N fertilizers (0.48 Tg.yr(-1)) is still
      incipient compared to the other two inputs mentioned above. The major output flux
      is the riverine flux, equal to 2.80 Tg.yr(-1) and export related to foodstuff,
      mainly the transport of soybean and beef to other parts of the country. The
      continuous population growth and high rate of urbanization may pose new threats
      to the nitrogen cycle of the region through the burning of fossil fuel and
      dumping of raw domestic sewage in rivers and streams of the region.

PMID- 23011299
TI  - Nitrogen cycle and ecosystem services in the Brazilian La Plata Basin:
      anthropogenic influence and climate change.
AB  - The increasing human demand for food, raw material and energy has radically
      modified both the landscape and biogeochemical cycles in many river basins in the
      world. The interference of human activities on the Biosphere is so significant
      that it has doubled the amount of reactive nitrogen due to industrial fertiliser
      production (Haber-Bosch), fossil fuel burning and land-use change over the last
      century. In this context, the Brazilian La Plata Basin contributes to the
      alteration of the nitrogen cycle in South America because of its huge
      agricultural and grazing area that meets the demands of its large urban centres -
      Sao Paulo, for instance - and also external markets abroad. In this paper, we
      estimate the current inputs and outputs of anthropogenic nitrogen (in kg N.km(
      2).yr(-1)) in the basin. In the results, we observe that soybean plays a very
      important role in the Brazilian La Plata, since it contributes with an annual
      entrance of about 1.8 TgN due to biological nitrogen fixation. Moreover, our
      estimate indicates that the export of soybean products accounts for roughly 1.0
      TgN which is greater than the annual nitrogen riverine exports from Brazilian
      Parana, Paraguay and Uruguay rivers together. Complimentarily, we built future
      scenarios representing changes in the nitrogen cycle profile considering two
      scenarios of climate change for 2070-2100 (based on IPCC's A2 and B2) that will
      affect land-use, nitrogen inputs, and loss of such nutrients in the basin.
      Finally, we discuss how both scenarios will affect human well-being since there
      is a connection between nitrogen cycle and ecosystem services that affect local
      and global populations, such as food and fibre production and climate regulation.

PMID- 23011300
TI  - Climate change in Brazil: perspective on the biogeochemistry of inland waters.
AB  - Although only a small amount of the Earth's water exists as continental surface
      water bodies, this compartment plays an important role in the biogeochemical
      cycles connecting the land to the atmosphere. The territory of Brazil encompasses
      a dense river net and enormous number of shallow lakes. Human actions have been
      heavily influenced by the inland waters across the country. Both biodiversity and
      processes in the water are strongly driven by seasonal fluvial forces and/or
      precipitation. These macro drivers are sensitive to climate changes. In addition
      to their crucial importance to humans, inland waters are extremely rich
      ecosystems, harboring high biodiversity, promoting landscape equilibrium
      (connecting ecosystems, maintaining animal and plant flows in the landscape, and
      transferring mass, nutrients and inocula), and controlling regional climates
      through hydrological-cycle feedback. In this contribution, we describe the
      aquatic ecological responses to climate change in a conceptual perspective, and
      we then analyze the possible climate-change scenarios in different regions in
      Brazil. We also indentify some potential biogeochemical signals in running
      waters, natural lakes and man-made impoundments. The possible future changes in
      climate and aquatic ecosystems in Brazil are highly uncertain. Inland waters are
      pressured by local environmental changes because of land uses, landscape
      fragmentation, damming and diversion of water bodies, urbanization, wastewater
      load, and level of pollutants can alter biogeochemical patterns in inland waters
      over a shorter term than can climate changes. In fact, many intense environmental
      changes may enhance the effects of changes in climate. Therefore, the maintenance
      of key elements within the landscape and avoiding extreme perturbation in the
      systems are urgent to maintain the sustainability of Brazilian inland waters, in
      order to prevent more catastrophic future events.

PMID- 23011301
TI  - Tracing latitudinal gradient, river discharge and water masses along the
      subtropical South American coast using benthic Foraminifera assemblages.
AB  - More than 30% of Buccella peruviana (D'Orbigny), Globocassidulina crassa porrecta
      (Earland & Heron-Allen), Cibicides mackannai (Galloway & Wissler) and C.
      refulgens (Montfort) indicate the presence of cold Sub Antarctic Shelf Water in
      winter, from 33.5 to 38.3o S, deeper than 100 m, in the southern part of the
      study area. In summer, the abundance of this association decreases to less than
      15% around 37.5-38.9o S where two species (Globocassidulina subglobosa (Brady),
      Uvigerina peregrina (Cushman) take over. G. subglobosa, U. peregrina, and
      Hanzawaia boueana (D'Orbigny) are found at 27-33o S in both seasons in less than
      55 m deep in the northern part, and are linked with warm Subtropical Shelf Water
      and Tropical Water. Freshwater influence was signalized by high silicate
      concentration and by the presence of Pseudononion atlanticum (Cushman), Bolivina
      striatula (Cushman), Buliminella elegantissima (D'Orbigny), Bulimina elongata
      (D'Orbigny), Elphidium excavatum (Terquem), E. poeyanum (D'Orbigny),
      Ammobaculites exiguus (Cushman & Bronnimann), Arenoparrella mexicana (Kornfeld),
      Gaudryina exillis (Cushman & Bronnimann), Textularia earlandi (Parker) and
      thecamoebians in four sectors of the shelf. The presence of Bulimina marginata
      (D'Orbigny) between 34.1-32.8o S in the winter and 34.2-32.7o S in the summer
      indicates that the influence of the Subtropical Shelf Front on the sediment does
      not change seasonally, otherwise, the presence of Angulogerina angulosa
      (Williamson) in the winter, only in Mar del Plata (38.9o S), show that Malvinas
      currents are not influencing the sediment in the summer.

PMID- 23011302
TI  - Land-sea interface features of four estuaries on the South America Atlantic
      coast.
AB  - The Brazilian coastal zone extends from 4o N to 34o S latitude and because of its
      long extension, the interface zone from continent to ocean includes a high
      diversity of geomorphologic and oceanographic characteristics. The rivers from
      the Northeast and East regions are marked by a typical unimodal seasonal flux
      patterns but with different amplitudes. As the climate indicates, the rivers from
      the Northeast are subject to an accentuated seasonal variability with an elevated
      input and flood pulses during the rainy season and low to negligible fluxes
      during the dry season. Small-scale rivers usually present typical torrential
      behaviour. In the humid eastern region, the unimodal seasonal cycle is dampened
      with a more constant input supply. Recently, some studies have shown that the
      material supply from rivers along the Northeast and Eastern coasts is diluted by
      surface tropical waters of oceanic currents and that the estuarine plume
      dispersal is restricted to a narrow coastal belt. However, human impacts of
      course mask or even override both natural hydrological cycles and CO2 emissions
      from terrestrial biomes, or depending on the nature of the human impact, can even
      increase extreme events. Henceforth this contribution addresses the typological,
      hydrological and biome diversity of the four estuarine systems fed and affected
      by the respective Amazon, Sao Francisco, Paraiba do Sul and Plata watersheds.

PMID- 23011305
TI  - Brazilian Journal of Biology. Editorial note.

PMID- 23011303
TI  - A review on soil carbon accumulation due to the management change of major
      Brazilian agricultural activities.
AB  - Agricultural areas deal with enormous CO2 intake fluxes offering an opportunity
      for greenhouse effect mitigation. In this work we studied the potential of soil
      carbon sequestration due to the management conversion in major agricultural
      activities in Brazil. Data from several studies indicate that in soybean/maize,
      and related rotation systems, a significant soil carbon sequestration was
      observed over the year of conversion from conventional to no-till practices, with
      a mean rate of 0.41 Mg C ha(-1) year(-1). The same effect was observed in
      sugarcane fields, but with a much higher accumulation of carbon in soil stocks,
      when sugarcane fields are converted from burned to mechanised based harvest,
      where large amounts of sugarcane residues remain on the soil surface (1.8 Mg C
      ha(-1) year(-1)). The higher sequestration potential of sugarcane crops, when
      compared to the others, has a direct relation to the primary production of this
      crop. Nevertheless, much of this mitigation potential of soil carbon accumulation
      in sugarcane fields is lost once areas are reformed, or intensive tillage is
      applied. Pasture lands have shown soil carbon depletion once natural areas are
      converted to livestock use, while integration of those areas with agriculture use
      has shown an improvement in soil carbon stocks. Those works have shown that the
      main crop systems of Brazil have a huge mitigation potential, especially in soil
      carbon form, being an opportunity for future mitigation strategies.

PMID- 23011308
TI  - Genetic characterization of bovine viral diarrhoea (BVD) viruses: confirmation of
      the presence of BVD genotype 2 in Africa.
AB  - Bovine viral diarrhoea virus (BVDV) has emerged as one of the economically
      important pathogens in cattle populations, with a worldwide distribution and
      causing a complex of disease syndromes. Two genotypes, BVDV 1 and 2, exist and
      are discriminated on the basis of the sequence of the 5' non-coding region (5'
      NCR) using real-time PCR. Real-time PCR is more sensitive, specific, and less
      time-consuming than conventional PCR, and it has less risk of cross-contamination
      of samples. Limited information exists on BVDV genetic subtypes in South Africa.
      The aim of this study was to determine the genotypes of BVDV currently
      circulating in South African feedlots. A total of 279 specimens (219 tissue
      samples, 59 trans-tracheal aspirates and 1 blood sample) were collected from dead
      and living cattle with lesions or clinical signs compatible with BVDV infection.
      Pooled homogenates from the same animals were prepared, and total RNA was
      extracted. A screening test was performed on the pooled samples, and positive
      pools were investigated individually. A Cador BVDV Type 1/2 RT-PCR Kit (QIAGEN,
      Hilden, Germany) was used for the real-time PCR assay on a LightCycler((r)) V2.0
      real-time PCR machine (Roche Diagnostics, Mannheim, Germany). The results were
      read at 530 and 640 nm for BVDV 1 and 2, respectively. Bovine viral diarrhoea
      virus was detected in a total of 103 samples that included 91 tissue samples, 1
      blood sample and 11 trans-tracheal aspirates. Eighty-five (82.5 %) of the strains
      were genotype 1 and 18 (17.5 %) were genotype 2. Comparing the sequencing data,
      genotypes 1 and 2 from the field strains did not cluster with vaccine strains
      currently used in feedlots in South Africa. The present study revealed the
      presence of BVDV genotype 2 in cattle in South Africa based on the high sequence
      similarity between genotype 2 field strains and strain 890 from North America.
      The presence of genotype 2 viruses that phylogenetically belong to different
      clusters and coexist in feedlots is consistent with the possibility of multiple
      virus introductions. These results represent the first documented evidence for
      the presence of BVDV genotype 2 in African cattle.

PMID- 23011306
TI  - Functional identification of the DNA packaging terminase from Pseudomonas
      aeruginosa phage PaP3.
AB  - Terminase proteins are responsible for DNA recognition and initiation of DNA
      packaging in phages. We previously reported the genomic sequence of a temperate
      Pseudomonas aeruginosa phage, PaP3, and determined its precise integration site
      in the host bacterial chromosome. In this study, we present a detailed functional
      identification of the DNA packaging terminase for phage PaP3. The purified large
      subunit p03 was demonstrated to possess ATPase and nuclease activities, as well
      as the ability to bind to specific DNA when it is unassembled. In addition, a
      small terminase subunit (p01) of a new type was found and shown to bind
      specifically to cos-containing DNA and stimulate the cos-cleavage and ATPase
      activities of p03. The results presented here suggest that PaP3 utilizes a
      typical cos site mechanism for DNA packaging and provide a first step towards
      understanding the molecular mechanism of the PaP3 DNA packaging reaction.

PMID- 23011307
TI  - Genetic characterization of parvoviruses circulating in turkey and chicken flocks
      in Poland.
AB  - Between 2008 and 2011, commercial turkey and chicken flocks in Poland were
      examined for the presence of turkey parvovirus (TuPV) and chicken parvovirus
      (ChPV). Clinical samples (10 individual faecal swabs/flock) from 197 turkey
      flocks (turkeys aged 1 to 19 weeks) and 45 chicken flocks (chickens aged 3 to 17
      weeks) were collected in different regions of the country and tested using a PCR
      assay that targeted the NS1 gene (3'ORF). The prevalence of TuPV was 29.4 % in
      the flocks tested, while ChPV infections were found in 22.2 % of the studied
      flocks. Phylogenetic analysis revealed a clear division into three groups: ChPV
      like, TuPV-like and a third, previously unrecognized and distinct subgroup, TuPV
      LUB, containing exclusively three Polish isolates from turkeys. The isolates from
      the novel group showed as little as 50.6-64.5 % of nucleotide sequence identity
      to the prototype chicken and turkey parvovirus strains. Genetic analysis of a
      ChPV isolate that was classified in the TuPV group strongly suggests a
      recombination event between chicken and turkey parvoviruses.

PMID- 23011310
TI  - Analysis of synonymous codon usage patterns in torque teno sus virus 1 (TTSuV1).
AB  - Torque teno sus virus 1 (TTSuV1) is a novel virus that has been found widely
      distributed in the swine population in recent years. Analysis of codon usage can
      reveal much about the molecular evolution of TTSuV1. In this study, synonymous
      codon usage patterns and the key determinants in the coding region of 29
      available complete TTSuV1 genome sequences were examined. By calculating the
      nucleotide content and relative synonymous codon usage (RSCU) of TTSuV1 coding
      sequences, we found that the preferentially used codons were mostly those ending
      with A or C nucleotides; less-used codons were mostly codons ending with U or G
      nucleotides, and these were mainly affected by composition constraints. Although
      there was a variation in codon usage bias among different TTSuV1 genomes, the
      codon usage bias and GC content in the TTSuV1 coding region was lower, which was
      mainly determined by the base composition in the third codon position and the
      effective number of codons (ENC) value. Moreover, the results of correspondence
      analysis (COA) indicated that the codon usage patterns of TTSuV1 isolated from
      different countries varied greatly and had significant differences. In addition,
      Spearman's rank correlation analysis and an ENC plot revealed that apart from
      mutation pressure, which was critical in determining the codon usage pattern,
      other factors were involved in shaping the evolution of codon usage bias in
      TTSuV1, such as natural selection. Those results suggested that synonymous codon
      usage patterns of TTSuV1 genomes were the result of interaction between mutation
      pressure and natural selection. The information from this study not only provides
      important insights into the synonymous codon usage pattern of TTSuV1, but also
      helps to identify the main factors affecting codon usage by this virus.

PMID- 23011309
TI  - A new mutation in the human cytomegalovirus UL97 gene may confer ganciclovir
      resistance in Chinese kidney transplant recipients.
AB  - Mutations in the UL97 gene are the most common mechanism of human cytomegalovirus
      resistance to ganciclovir in transplant recipients. In this study, UL97 fragments
      were amplified and sequenced in 70 Chinese kidney transplant recipients who were
      diagnosed as having an active cytomegalovirus infection. A new mutation, C518Y,
      was identified in two kidney recipients, and this strain showed high-grade
      ganciclovir resistance by plaque reduction assay. The known mutations L595 W and
      C607F were detected in one recipient, but the D605E mutation was found in 42.9 %
      (30/70) of kidney recipients. The prevalence of this mutation was higher than
      that in Europe and may be associated with different regions or races.

PMID- 23011311
TI  - High prevalence of amantadine-resistant influenza A virus isolated in Gyeonggi
      Province, South Korea, during 2005-2010.
AB  - Amantadine resistance among influenza A viruses was investigated in South Korea
      in 2005-2010. Of 308 influenza A viruses examined, 229 had the S31N substitution
      in the M2 protein. The frequency of amantadine resistance was 30 %, 100 %, and 76
      % in influenza A/H1N1, pandemic A/H1N1 2009(A/H1N1pdm), and A/H3N2 subtypes,
      respectively. The amantadine-resistant influenza A/H1N1pdm and A/H3N2 viruses
      were circulating continuously from 2008 to 2009 and from 2005 to 2006,
      respectively. Amantadine resistance among influenza A viruses increased
      dramatically during the 5-year study period, and this has diminished the
      usefulness of this class of drugs.

PMID- 23011312
TI  - Pathogen-derived resistance using a viral nucleocapsid gene confers only partial
      non-durable protection in peanut against peanut bud necrosis virus.
AB  - Genetic engineering of peanut (Arachis hypogaea L.) using the gene encoding for
      the nucleocapsid protein (N gene) of peanut bud necrosis virus (PBNV; genus
      Tospovirus, family Bunyaviridae) was used to impart resistance to bud necrosis
      disease in peanut (PBND), a disease for which no durable resistance is available
      in the existing germplasm. Over 200 transgenic lines of peanut var. JL 24 were
      developed for which integration and expression of the transgenes was confirmed by
      PCR, Southern hybridization, RT-PCR and western blot analysis. The T(1) and T(2)
      generation transgenic plants were assayed through virus challenge in the
      greenhouse by using mechanical sap inoculation at 1:100 and 1:50 dilutions of
      PBNV, and they showed varying levels of disease incidence and intensity.
      Greenhouse and field evaluation with T(2) generation plants indicated somewhat
      superior performance of the three transgenic events that showed considerable
      reduction in disease incidence. However, only one of these events showed over 75
      % reduction in disease incidence when compared to the untransformed control,
      indicating partial and non-durable resistance to PBND using the viral N-gene.

PMID- 23011313
TI  - Iristectorigenin B isolated from Belamcanda chinensis is a liver X receptor
      modulator that increases ABCA1 and ABCG1 expression in macrophage RAW 264.7
      cells.
AB  - A novel liver X receptor (LXR) modulator, iristectorigenin B isolated from
      Belamcanda chinensis, stimulated the transcriptional activity of both LXR-alpha
      and LXR-beta. In macrophages, iristectorigenin B suppressed cholesterol
      accumulation in a dose-dependent manner and induced the transcriptional
      activation of LXR-alpha/-beta-responsive genes, ATP-binding cassette transporters
      A1 and G1. It did not induce hepatic lipid accumulation nor the expression of the
      lipogenesis genes sterol regulatory element-binding protein-1c, fatty acid
      synthase, and stearoyl-CoA desaturase-1. Iristectorigenin B thus is a dual-LXR
      agonist that regulates the expression of key genes in cholesterol homeostasis in
      macrophage cells without inducing hepatic lipid accumulation.

PMID- 23011314
TI  - A series of goblet-like heterometallic pentanuclear [Ln(III)Cu(II)4] clusters
      featuring ferromagnetic coupling and single-molecule magnet behavior.
AB  - A series of fascinating goblet-like clusters based on [Ln(III)Cu(II)(4)] cores
      have been assembled from a flexible carboxylate ligand, which exhibit a dominant
      ferromagnetic exchange coupling and single-molecule magnet behavior.

PMID- 23011315
TI  - Statistical identification of syndromes feature and structure of disease of
      western medicine based on general latent structure model.
AB  - Syndrome differentiation is the character of Chinese medicine (CM). Disease
      differentiation is the principle of Western medicine (WM). Identifying basic
      syndromes feature and structure of disease of WM is an important avenue for
      prevention and treatment of integrated Chinese and Western medicine. The idea
      here is first to divide all patients suffering from a disease of WM into several
      groups in the light of the stage of the disease, and secondly to identify basic
      syndromes feature in a distinct stage, and finally to achieve the purpose of
      syndrome differentiation. Syndrome differentiation is simply taken as a
      classifier that classifies patients into distinct classes primarily based on
      overall observation of their symptoms. Previous clustering methods are unable to
      cope with the complexity of CM. We therefore show a new multi-dimensional
      clustering method in the form of general latent structure (GLS) model, which is a
      suitable statistical learning technique of latent class analysis. In this paper,
      we learn an optimal GLS model which reflects much better model quality compared
      with other latent class models from the osteoporosis patient of community women
      (OPCW) real data including 40-65 year-old women whose bone mineral density (BMD)
      is less than mean-2.0 standard deviation (M-2.0SD). Further, we illustrate a case
      analysis of statistical identification of CM syndromes feature and structure of
      OPCW from qualitative and quantitative contents through the GLS model. Our
      analysis has discovered natural clusters and structures that correspond well to
      CM basic syndrome and factors of osteoporosis patients (OP). The GLS model
      suggests the possibility of establishing objective and quantitative diagnosis
      standards for syndrome differentiation on OPCW. Hence, for the future it can
      provide a reference for the similar study from the perspective of a combination
      of disease differentiation and syndrome differentiation.

PMID- 23011316
TI  - Identification of combining ability loci for five yield-related traits in maize
      using a set of testcrosses with introgression lines.
AB  - Combining ability is essential for hybrid breeding in crops. However, the genetic
      basis of combining ability remains unclear and has been seldom investigated.
      Identifying molecular markers associated with this complex trait would help to
      understand its genetic basis and provide useful information for hybrid breeding
      in maize. In this study, we identified genetic loci of general combining ability
      (GCA) and specific combining ability (SCA) for five yield-related traits under
      three environments using a set of testcrosses with introgression lines (ILs). GCA
      or SCA of the five yield-related traits of the ILs was estimated by the
      performance of testcrosses with four testers from different heterotic groups.
      Genetic correlations between GCA of the traits and the corresponding traits per
      se were not significant or not strong, suggesting that the genetic basis between
      them is different. A total of 56 significant loci for GCA and 21 loci for SCA
      were commonly identified in at least two environments, and only 5 loci were
      simultaneously controlling GCA and SCA, indicating that the genetic basis of GCA
      and SCA is different. For all of the traits investigated, positive and
      significant correlations between the number of GCA loci in the ILs and the
      performance of the corresponding GCA of the ILs were detected, implying that
      pyramiding GCA loci would have positive effect on the performance of GCA. Results
      in this study would be useful for maize hybrid breeding.

PMID- 23011317
TI  - Case scenario: anesthesia-related cardiac arrest in a child with Timothy
      syndrome.

PMID- 23011318
TI  - Neuromuscular monitoring: more than meets the eye.

PMID- 23011320
TI  - Daytime measurements underestimate nocturnal oxygen desaturations in pulmonary
      arterial and chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Nocturnal hypoxemia is important in precapillary pulmonary
      hypertension (pPH) as it worsens pulmonary hemodynamics. Whether daytime oxygen
      saturation (SpO(2)) predicts nocturnal hypoxemia in pPH patients has not been
      conclusively studied. OBJECTIVES: To investigate the prevalence of nocturnal
      hypoxemia in comparison to daytime SpO(2) and disease severity in ambulatory
      patients with pulmonary hypertension. METHODS: Consecutive patients diagnosed
      with pPH classified as either pulmonary arterial (PAH) or chronic thromboembolic
      pPH (CTEPH) had daytime resting and exercise SpO(2) (at the end of a 6-min walk
      test); thereafter, they underwent overnight pulse oximetry at home. Functional
      class, pro-brain natriuretic peptide (pro-BNP) and the tricuspid pressure
      gradient were assessed. RESULTS: Sixty-three patients [median (quartiles) age 62
      (53; 71), 43 females] with PAH (n = 44) and CTEPH (n = 19) were included. The
      resting SpO(2), exercise SpO(2), and mean nocturnal SpO(2) were 95% (92; 96), 88%
      (81; 95), and 89% (85; 92), respectively. Forty-nine patients (77%) spent >10% of
      the night with SpO(2) <90% (desaturators), and 33 (52%) spent >50% of the night
      with SpO(2) <90% (sustained desaturators). The positive predictive values of
      daytime SpO(2) >90% for being a nocturnal nondesaturator or sustained
      nondesaturator were 25 and 53%, respectively. Nocturnal SpO(2) was negatively
      correlated with the tricuspid pressure gradient, but not with functional class, 6
      min walk test, or pro-BNP. CONCLUSIONS: Nocturnal hypoxemia is very common in PAH
      and CTEPH despite often normal daytime SpO(2) and reflects disease severity.
      Nocturnal pulse oximetry should be considered in the routine evaluation of pPH
      patients and research should be directed toward the treatment of nocturnal
      desaturation in pPH.

PMID- 23011321
TI  - The acute effect of fludrocortisone on basal and hCRH-stimulated hypothalamic-
      pituitary--adrenal (HPA) axis in humans.
AB  - Mineralocorticoid receptors (MR) in the hippocampus display an important role in
      the control of hypothalamic-pituitary-adrenal (HPA)-axis, mediating the
      "proactive"-feedback of glucocorticoids. Fludrocortisone (FC), a potent MR
      agonist, has been shown to decrease HPA activity through a mechanism placed at
      hippocampal level. In order to clarify the effects of MR agonism on HPA function
      in humans, we studied the effects of FC, in a dose-related manner, on both basal
      and CRH-stimulated HPA axis during the quiescent phase. 8 young women were
      studied. ACTH, cortisol and aldosterone levels were evaluated every 15', from
      1600 to 2000 hours, in randomized sessions: (1) placebo p.o. + placebo i.v., (2)
      0.3 mg FC p.o. + placebo, (3) 0.1 mg FC. + placebo, (4) 0.075 mg FC + placebo,
      (5) 0.05 mg FC + placebo, (6) placebo + hCRH (2.0 MUg/kg iv-bolus), (7) 0.3 mg FC
      + hCRH, (8) 0.1 mg FC + hCRH, (9) 0.075 mg FC + hCRH, (10) 0.05 mg FC + hCRH. FC
      induced a dose-related trend toward a further decrease of the ACTH and cortisol
      levels, while it showed a significant and dose-dependent inhibition of the
      hormonal response to hCRH (p < 0.05 for the doses of 0.3, 0.1 and 0.075 mg).
      Conversely, 0.05 mg FC did not modify the CRH-stimulatory effect on both ACTH and
      cortisol secretion. Aldosterone levels were not modified by FC administration.
      Fludrocortisone inhibits corticotrope and adrenal response to hCRH in humans, in
      a dose-dependent manner. The 0.075 mg FC seems the lowest active while 0.05 mg
      the first neutral dose on HPA activity. These data suggest a possible hypophysial
      MR-mediated inhibiting effect of FC, although its pituitary glucocorticoid
      mediated effect cannot be excluded. The interplay between fludrocortisone and
      hypophysial glucocorticoid receptors needs to be clarified in order to define
      better the clinical consequences of the hormonal replacement therapy of patients
      with primary adrenal insufficiency.

PMID- 23011323
TI  - [Non-destructive ultrasonic technique of enamel thickness measurement].
AB  - An ultrasonic technique of enamel thickness measurement has been proposed. In
      this technique, a thin tray with a hole is placed on the surface of the tooth and
      the tip of the ultrasonic probe is inserted in this hole to prevent lateral shift
      of the tip during adjustment of angular position of the probe. Results of the
      ultrasonic measurements carried out on the extracted teeth with the enamel layer
      thickness in a range of 1-0.3 mm and the inclination angle up to 0.1 show that
      the relative thickness measurement error does not exceed +/- 2-3%. Typical
      deviation between the ultrasonic data and the results of the destructive
      evaluation of the specimens is about +/- 0.05 mm.

PMID- 23011324
TI  - [Reparative regeneration and adaptive remodeling of the mandible by transosseous
      osteosynthesis].
AB  - Mandibular injuries are the most common pathology of facial the skeleton. The aim
      of the study was to substantiate the effectiveness of treatment of this pathology
      using transosseous osteosynthesis method from the experimental and morphological
      point of view. The formation of bone union of mandibular fragments has been
      confirmed experimentally in 27 adult mongrel dogs after a month of fixation by
      the device and within a month after its demounting. The fibrous-and-connective
      union of full functional value has been formed in the zone of mandibular junction
      rupture in the same periods.

PMID- 23011322
TI  - Single-surgeon fully endoscopic endonasal transsphenoidal surgery: outcomes in
      three-hundred consecutive cases.
AB  - The objective of this study was to evaluate outcomes of endoscopic
      transsphenoidal surgery using a single-surgeon technique as an alternative to the
      more commonly employed two-surgeon, three-hand method. Three hundred consecutive
      endoscopic transsphenoidal procedures performed over a 5 year period from 2006 to
      2011 were reviewed. All procedures were performed via a binasal approach
      utilizing a single surgeon two handed technique with a pneumatic endoscope
      holder. Expanded enodnansal cases were excluded. Surgical technique, biochemical
      and surgical outcomes, and complications were analyzed. 276 patients underwent
      300 consecutive surgeries with a mean follow-up period of 37 +/- 22 months. Non
      functioning pituitary adenoma (NFPA) was the most common pathology (n = 152),
      followed by growth hormone secreting tumors (n = 41) and Rathke's cleft cysts (n
      = 30). Initial gross total cyst drainage based on radiologic criteria was
      obtained in 28 cases of Rathke's cleft cyst, with 5 recurrences. For NFPA and
      other pathologies (n = 173) gross total resection was obtained in 137 cases, with
      a 92% concordance rate between observed and expected extent of resection. For
      functional adenoma, remission rates were 30/41 (73%) for GH-secreting, 12/12
      (100%) for ACTH-secreting, and 8/17 (47%) for prolactin-secreting tumors. Post
      operative complications included transient (11%) and permanent (1.4%) diabetes
      insipidus, hyponatremia (13%), and new anterior pituitary hormonal deficits
      (1.4%). CSF leak occurred in 42 cases (15%), and four patients required surgical
      repair. Two carotid artery injuries occurred, both early in the series. Epistaxis
      and other rhinological complications were noted in 10% of patients, most of which
      were minor and diminished as surgical experience increased. Fully endoscopic
      single surgeon transsphenoidal surgery utilizing a binasal approach and a
      pneumatic endoscope holder yields outcomes comparable to those reported with a
      two-surgeon method. Endoscopic outcomes appear to be better than those reported
      in microscope-based series, regardless of a one or two surgeon technique.

PMID- 23011325
TI  - [General and local factors affecting periapical reparation after endodontic
      procedures].
AB  - Eighty-seven teeth with 100 periapical destruction foci have been treated in 78
      patients from 19 to 60 years of age. In 28 patients calcium-containing
      preparation was administrated orally for 1 to 3 months. The dynamics of
      destruction foci changes was similar in all patients though among patients with
      satisfactory X-ray findings 64% took calcium-containing preparation. No
      considerable difference in the regeneration dynamics was revealed in patients
      with somatic diseases and healthy individuals. The residual destruction size 12
      months later correlated positively with the initial size of destruction area.

PMID- 23011326
TI  - [Crystallographic picture of the gingival fluid in healthy teeth and by
      inflammatory periodontal disease].
AB  - The research revealed crystallographic structure of the gingival fluid in healthy
      teeth and by inflammatory periodontal disease. Comparing the results with
      clinical data both crystallographic patterns in healthy teeth gingival fluid and
      markers of periodontal tissue pathology were established.

PMID- 23011327
TI  - [Improving diagnostics of leukoplakia].
AB  - The study included 32 patients (among them 20 patients with simple and 12 with
      verrucous leukoplakia) and presents both classic and advanced diagnostic methods
      for this disease: clinical examination, histological and immunohistochemical
      studies. The latter allows revealing neoplastic transformation of the oral
      mucosa.

PMID- 23011328
TI  - [Artemisia absinthium L. in complex treatment of inflammatory periodontal
      disease].
AB  - The effectiveness of Artemisia absinthium L. in complex treatment of inflammatory
      periodontal disease was assessed in the study by ELIZA evaluation of PGE2 in
      mixed saliva. Microcirculation in periodontal tissues was also assessed by means
      of laser Doppler flowmetry. It was found out that complex treatment involving
      Artemisia absinthium L. improves microcirculation in periodontal tissues and
      reduces inflammation.

PMID- 23011329
TI  - [Surgical tactics by various ameloblastic tumors].
AB  - Ameloblastoma and ameloblastic fibroma are benign odontogenous tumors of the jaws
      with local destructive growth, prone to recurrence. They have various typical
      radiological and histological features. Surgical tactic generally includes
      partial resection of the affected jaw. Immunohistochemical study of the tumor
      tissues allows assessing the expression of tumor progression markers and
      forecasting tumor growth thus providing individual choice of surgical tactics.
      Our experience in treatment of ameloblastic tumors showed total biopsy with
      osseous surgical margins resection to be sufficient for normal bone structure
      remodeling in some patients.

PMID- 23011330
TI  - [Oral SCC regional metastatic disease patterns revealed by preventive neck
      dissections].
AB  - One hundred and seventy-two preventive neck dissections were performed in 159
      oral SCC patients. The study revealed the possibility of skip metastases in the
      lower cervical lymphatic nodes thus confirming the necessity for their removal in
      elective neck dissections.

PMID- 23011331
TI  - [Bone tissue restoration after tooth removal by means of tissue-engineering
      construction based on multipotent stromal adipose cells].
AB  - The paper contains clinical examples of tissue-engineering construction based on
      multipotent stromal adipose cells application for tooth socket healing. The
      method do not only prevents the bone tissue resorption but allows recreating its
      volume.

PMID- 23011332
TI  - [Antioxidant therapy by infectious complication of oral surgery procedures].
AB  - The study presents the results of prevention and treatment of infectious and
      inflammatory complications after oral surgery procedures. Combined therapy with
      antibiotics and superlimf promotes a more rapid reduction in the duration of
      clinical symptoms and duration of treatment than monotherapy with antibiotics.
      Results of the study substantiate the feasibility of using superlimf in
      outpatient oral surgical procedures for infectious and inflammatory complications
      treatment.

PMID- 23011333
TI  - [Antihomotoxic therapy in patients with inflammatory and dystrophic salivary
      gland diseases].
AB  - Traumeel S was used as monotherapy for salivary glands inflammatory and
      dystrophic disorders. The study showed the drug to be especially efficient by
      exacerbation of the recurrent disease but the results were poor by indolent
      disease and on the latter stages of dystrophic disorder. Traumel S may be
      recommended to be used in combined therapy for salivary glands inflammatory and
      dystrophic disorders treatment.

PMID- 23011334
TI  - [Soft tissue contour changes in restorative rehabilitation by complete dentures].
AB  - Virtual 3D models were made on the stages of prosthodontic treatment by upper
      complete dentures. Anthropometric points were marked on the lower third of the
      face and soft tissue contour changed were studied. The study results showed the
      vestibular surface of the occlusion rim may be used for computer design of
      removable complete dentures.

PMID- 23011335
TI  - [Microcirculation dynamics in marginal gingiva by its contouring after second
      stage of dental implantation].
AB  - Microcirculation dynamics in marginal gingiva by its contouring after second
      stage of dental implantation was examined by means of laser Doppler flowmetry.
      After installation of the 5.5 mm flared healing abutments there was a significant
      reduction in tissue blood flow indicating severe ischemia in marginal gingiva.
      Efficient prosthodontic treatment caused beneficial impact on microcirculation.

PMID- 23011336
TI  - [Periodontal tissue spectral assessment].
AB  - The periodontal condition was investigated by means of tooth natural frequency
      assessment. The correlation between tooth natural frequency and mobility was
      found out. The comparative estimation of percussion and spectral methods for
      natural frequency assessment revealed the percussion method to be more
      complicates because the initial acoustic signal is disturbed by external noises
      and hammer sound. The spectral method allows receiving reliable and reproducible
      results when using modified two-parametrical periodontometer.

PMID- 23011337
TI  - [Morphofunctional tongue features revealed by multispiral CT in cleft lip and
      palate patients].
AB  - Tongue structure and position as well as oral cavity volume were analyzed by
      means of multispiral CT in 82 cleft lip and palate patients and 27 healthy
      children. The study revealed microglossia and anomalous position and form of the
      tongue causing tongue tip to be pressed to the incisal part of the lower alveolar
      bone not exerting physiological impact on the upper alveolar bone. These results
      confirm the tongue position to be one of the factors for occlusion abnormalities
      in cleft lip and palate patients.

PMID- 23011338
TI  - [10-years caries incidence and intensity dynamics in pregnant women of Derbent
      city].
AB  - Caries incidence was assessed in pregnant women in 1998, 2003 an 2008 showing the
      values to be stable. DMF was almost the same in 1998 and 2003, but in 2008 the
      rate of "F" (filled) element was significantly higher thus confirming growth in
      motivation for dental treatment after introduction of private dental practices.

PMID- 23011339
TI  - [Standards in dentistry - state of the art].

PMID- 23011340
TI  - Chromatin: Defining heterochromatin.

PMID- 23011341
TI  - Non-coding RNAS: A new member of the family.

PMID- 23011344
TI  - Effects of noise on models of spiny dendrites.
AB  - We study the effects of noise in two models of spiny dendrites. Through the
      introduction of different types of noise to both the Spike-diffuse-spike (SDS)
      and Baer-Rinzel (BR) models we investigate the change in behaviour of the
      travelling wave solution present in both deterministic systems, as noise
      intensity increases. We show that the speed of wave propagation in both the SDS
      and BR models respectively differs as the noise intensity in the spine heads
      increases. In contrast the cable is very robust to noise and as such the speed
      shows very little variation from the deterministic system. We introduce a space
      dependent spine density, rho(x), to the original Baer-Rinzel model and show how
      this modified model can mimic behaviour (under influence of noise) of both
      original systems, through variation of one parameter. We also show that the
      correlation time and length scales of the noise can enhance propagation of
      travelling wave solutions where the white noise dominates the underlying signal
      and produces noise induced phenomena.

PMID- 23011345
TI  - Bimetallic catalysts for hydrogen generation.
AB  - Research interest in bimetallic catalysts is mainly due to their tunable
      chemical/physical properties by a number of parameters like composition and
      morphostructure. In catalysis, numerous bimetallic catalysts have been shown to
      exhibit unique properties which are distinct from those of their monometallic
      counterparts. To meet the growing energy demand while mitigating the
      environmental concerns, numerous endeavors have been made to seek green and
      sustainable energy resources, among which hydrogen has been identified as the
      most promising one with bimetallic catalysts playing important roles. This
      tutorial review intends to summarize recent progress in bimetallic catalysts for
      hydrogen production, specifically focusing on that of reforming technologies as
      well as the relevant processes like water-gas shift (WGS) and CO preferential
      oxidation (PROX), and emphasizing on the fundamental understanding of the nature
      of catalytic sites responsible for generating high purity hydrogen and minimizing
      carbon monoxide formation. Meanwhile, some important synthesis and
      characterization methods of bimetallic catalysts developed so far are also
      summarized.

PMID- 23011343
TI  - Nonlinear modeling of dynamic interactions within neuronal ensembles using
      Principal Dynamic Modes.
AB  - A methodology for nonlinear modeling of multi-input multi-output (MIMO) neuronal
      systems is presented that utilizes the concept of Principal Dynamic Modes (PDM).
      The efficacy of this new methodology is demonstrated in the study of the dynamic
      interactions between neuronal ensembles in the Pre-Frontal Cortex (PFC) of a
      behaving non-human primate (NHP) performing a Delayed Match-to-Sample task.
      Recorded spike trains from Layer-2 and Layer-5 neurons were viewed as the
      "inputs" and "outputs", respectively, of a putative MIMO system/model that
      quantifies the dynamic transformation of multi-unit neuronal activity between
      Layer-2 and Layer-5 of the PFC. Model prediction performance was evaluated by
      means of computed Receiver Operating Characteristic (ROC) curves. The PDM-based
      approach seeks to reduce the complexity of MIMO models of neuronal ensembles in
      order to enable the practicable modeling of large-scale neural systems
      incorporating hundreds or thousands of neurons, which is emerging as a preeminent
      issue in the study of neural function. The "scaling-up" issue has attained
      critical importance as multi-electrode recordings are increasingly used to probe
      neural systems and advance our understanding of integrated neural function. The
      initial results indicate that the PDM-based modeling methodology may greatly
      reduce the complexity of the MIMO model without significant degradation of
      performance. Furthermore, the PDM-based approach offers the prospect of improved
      biological/physiological interpretation of the obtained MIMO models.

PMID- 23011346
TI  - Dependence of structure stability and integrity of aerobic granules on ATP and
      cell communication.
AB  - Aerobic granules are dense and compact microbial aggregates with various
      bacterial species. Recently, aerobic granulation technology has been extensively
      explored for treatment of municipal and industrial wastewaters. However, little
      information is currently available with regard to their structure stability and
      integrity at levels of energy metabolism and cell communication. In the present
      study, a typical chemical uncoupler, 3,3',4',5-tetrachlorosalicylanilide with the
      power to dissipate proton motive force and subsequently inhibit adenosine
      triphosphate (ATP) generation, was used to investigate possible roles of ATP and
      cell communication in maintaining the structure stability and integrity of
      aerobic granules. It was found that inhibited ATP synthesis resulted in the
      reduced production of autoinducer-2 and N-acylhomoserine lactones essential for
      cell communication, while lowered extracellular polymeric substance (EPS)
      production was also observed. As a consequence, aerobic granules appeared to
      break up. This study showed that ATP-dependent quorum sensing and EPS were
      essential for sustaining the structure stability and integrity of aerobic
      granules.

PMID- 23011347
TI  - Biosorption of heavy metals in a photo-rotating biological contactor--a batch
      process study.
AB  - Metal removal potential of indigenous mining microorganisms from acid mine
      drainage (AMD) has been well recognised in situ at mine sites. However, their
      removal capacity requires to be investigated for AMD treatment. In the reported
      study, the capacity of an indigenous AMD microbial consortium dominated with
      Klebsormidium sp., immobilised in a photo-rotating biological contactor (PRBC),
      was investigated for removing various elements from a multi-ion synthetic AMD.
      The synthetic AMD was composed of major (Cu, Mn, Mg, Zn, Ca, Na, Ni) and trace
      elements (Fe, Al, Cr, Co, Se, Ag, Mo) at initial concentrations of 2 to 100 mg/L
      and 0.005 to 1 mg/L, respectively. The PRBC was operated for two 7-day batch
      periods under pH conditions of 3 and 5. The maximum removal was observed after 3
      and 6 days at pH 3 and 5, respectively. Daily water analysis data demonstrated
      the ability of the algal-microbial biofilm to remove an overall average of 25-40
      % of the major elements at pH 3 in the order of Na > Cu > Ca > Mg > Mn > Ni > Zn,
      whereas a higher removal (35-50 %) was observed at pH 5 in the order of Cu > Mn >
      Mg > Ca > Ni > Zn > Na. The removal efficiency of the system for trace elements
      varied extensively between 3 and 80 % at the both pH conditions. The batch data
      results demonstrated the ability for indigenous AMD algal-microbial biofilm for
      removing a variety of elements from AMD in a PRBC. The work presents the
      potential for further development and scale-up to use PBRC inoculated with AMD
      microorganisms at mine sites for first or secondary AMD treatment.

PMID- 23011348
TI  - Polyaniline-assisted silver nanoparticles: a novel support for the immobilization
      of alpha-amylase.
AB  - The size distribution of nanomaterials and their similarity in size with enzyme
      molecules together with other advantageous properties such as thermal stability,
      high surface-to-volume ratio, and irradiation resistance have revolutionized
      nanobiocatalytic approaches in various areas of enzyme technology. In the present
      study, polyaniline-assisted Ag nanocomposites were synthesized using ammonium
      peroxydisulfate as oxidant. These nanocomposites were used as a support for the
      covalent conjugation of alpha-amylase, one of the important industrial enzymes. X
      ray diffraction study showed that the crystalline nature of nanocomposites was
      increased in the presence of Ag nanoparticles. Thermogravimetric and differential
      thermal analysis revealed that the synthesized nanocomposites retained
      significantly very high thermal stability. Scanning electron micrograph showed
      that Ag nanoparticles were homogeneously dispersed in polyaniline film providing
      large surface area and microenvironment for enzyme loading. Fourier transform
      infrared spectroscopy confirmed the conjugation of alpha-amylase to the
      functionalized nanocomposites. The conjugated alpha-amylase exhibited better
      tolerance to variations in the medium pH and temperature compared with the native
      enzyme. Immobilized alpha-amylase hydrolyzes starch more efficiently as compared
      to the free enzyme in batch process.

PMID- 23011349
TI  - alpha-Fucosidases with different substrate specificities from two species of
      Fusarium.
AB  - Two fungal-secreted alpha-fucosidases and their genes were characterized. FoFCO1
      was purified from culture filtrates of Fusarium oxysporum strain 0685 grown on L
      fucose and its encoding gene identified in the sequenced genome of strain 4287.
      FoFCO1 was active on p-nitrophenyl-alpha-fucoside (pNP-Fuc), but did not
      defucosylate a nonasaccharide (XXFG) fragment of pea xyloglucan. A putative alpha
      fucosidase gene (FgFCO1) from Fusarium graminearum was expressed in Pichia
      pastoris. FgFCO1 was ~1,800 times less active on pNP-Fuc than FoFCO1, but was
      able to defucosylate the XXFG nonasaccharide. Although FgFCO1 and FoFCO1 both
      belong to Glycosyl Hydrolase family 29, they share <25 % overall amino acid
      identity. Alignment of all available fungal orthologs of FoFCO1 and FgFCO1
      indicated that these two proteins belong to two subfamilies of fungal GH29 alpha
      fucosidases. Fungal orthologs of subfamily 1 (to which FoFCO1 belongs) are
      taxonomically more widely distributed than subfamily 2 (FgFCO1), but neither was
      universally present in the sequenced fungal genomes. Trichoderma reesei and most
      species of Aspergillus lack genes for either GH29 subfamily.

PMID- 23011350
TI  - Inhibition of activin/nodal signalling is necessary for pancreatic
      differentiation of human pluripotent stem cells.
AB  - AIMS/HYPOTHESIS: Human embryonic stem cells (hESCs) and human induced pluripotent
      stem cells (hIPSCs) offer unique opportunities for regenerative medicine and for
      the study of mammalian development. However, developing methods to differentiate
      hESCs/hIPSCs into specific cell types following a natural pathway of development
      remains a major challenge. METHODS: We used defined culture media to identify
      signalling pathways controlling the differentiation of hESCs/hIPSCs into
      pancreatic or hepatic progenitors. This approach avoids the use of feeders,
      stroma cells or serum, all of which can interfere with experimental outcomes and
      could preclude future clinical applications. RESULTS: This study reveals, for the
      first time, that activin/TGF-beta signalling blocks pancreatic specification
      induced by retinoic acid while promoting hepatic specification in combination
      with bone morphogenetic protein and fibroblast growth factor. Using this
      knowledge, we developed culture systems to differentiate human pluripotent stem
      cells into near homogenous population of pancreatic and hepatic progenitors
      displaying functional characteristics specific to their natural counterparts.
      Finally, functional experiments showed that activin/TGF-beta signalling achieves
      this essential function by controlling the levels of transcription factors
      necessary for liver and pancreatic development, such as HEX and HLXB9.
      CONCLUSION/INTERPRETATION: Our methods of differentiation provide an advantageous
      system to model early human endoderm development in vitro, and also represent an
      important step towards the generation of pancreatic and hepatic cells for
      clinical applications.

PMID- 23011351
TI  - Effects of 12 weeks' treatment with a proton pump inhibitor on insulin secretion,
      glucose metabolism and markers of cardiovascular risk in patients with type 2
      diabetes: a randomised double-blind prospective placebo-controlled study.
AB  - AIMS/HYPOTHESIS: Recent studies suggest that proton pump inhibitor treatment may
      increase insulin secretion and improve glucose metabolism in type 2 diabetes. In
      a randomised double-blind prospective placebo-controlled 2 * 2 factorial study,
      we examined the effect of esomeprazole on insulin secretion, HbA(1c) and
      cardiovascular risk factors in type 2 diabetes. METHODS: Forty-one patients with
      type 2 diabetes using dietary control or oral glucose-lowering treatment were
      randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for
      12 weeks. Randomisation was carried out prior to inclusion on the basis of a
      computer-generated random-number list. The allocation sequence was concealed in
      sealed envelopes from the researcher enrolling and assessing participants. The
      study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary
      outcome was change in AUC for insulin levels during a meal test. Secondary
      outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular
      risk, including lipids, coagulation factors, inflammation markers, markers of
      endothelial function and 24 h ambulatory BP measurements. RESULTS: Forty-one
      participants were analysed. In the esomeprazole-treated group the AUC for insulin
      did not change (before vs after treatment: 28,049 +/- 17,659 vs 27,270 +/- 32,004
      pmol/l * min (p = 0.838). In the placebo group AUC for insulin decreased from
      27,392 +/- 14,348 pmol/l * min to 22,938 +/- 11,936 pmol/l * min (p = 0.002).
      Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for
      gastrin. HbA(1c) increased from 7.0 +/- 0.6% (53 +/- 5 mmol/mol) to 7.3 +/- 0.8%
      (56 +/- 6 mmol/mol) in the esomeprazole-treated group and from 7.0 +/- 0.6% (53
      +/- 5 mmol/mol) to 7.4 +/- 0.8% (57 +/- 6 mmol/mol) in the placebo group (n = 21)
      (p for difference in change >0.05). Except for BP, there were no differences
      between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring
      of 24 h ambulatory BP showed a significant decrease in daytime systolic BP,
      daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No
      change in BP was seen in the patients treated with esomeprazole.
      CONCLUSIONS/INTERPRETATION: Treatment with esomeprazole over 12 weeks did not
      improve insulin secretion, glycaemic control or cardiovascular disease biomarkers
      in patients with type 2 diabetes.

PMID- 23011352
TI  - Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in
      conjunction with dipeptidyl peptidase 4 inhibition.
AB  - AIMS/HYPOTHESIS: We have shown that chronic administration of the Toll-like
      receptor 2 (TLR2) agonist Pam3CSK(4) prevents diabetes in NOD mice by inducing
      TLR2 tolerance of dendritic cells (DCs). We have also reported that a novel
      dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1229, could increase beta cell mass.
      Here we investigated whether a combination of DPP4 inhibition, with beneficial
      effects on beta cell mass, and TLR2 tolerisation, protecting beta cells from
      autoimmune destruction, could treat a model of established type 1 diabetes.
      METHODS: Diabetic NOD mice were treated with 100 MUg Pam3CSK(4), administered
      three times a week for 3 weeks, in combination with feeding with chow containing
      0.3% DA-1229. Beta cell mass and proliferation were studied by
      immunohistochemistry. DC tolerance was assessed by studying diabetogenic CD4(+) T
      cell priming after adoptive transfer and expression of costimulatory molecules on
      DCs by flow cytometry. RESULTS: We observed reversal of diabetes in NOD mice by
      Pam3CSK(4)+DA-1229 but not by either Pam3CSK(4) or DA-1229 alone. Beta cell mass
      and the number of proliferating beta cells were significantly enhanced by
      Pam3CSK(4)+DA-1229, but not by either Pam3CSK(4) or DA-1229 alone. Diabetogenic T
      cell priming by DCs and upregulation of costimulatory molecules after ex vivo
      stimulation were attenuated in mice treated with Pam3CSK(4)+DA-1229, indicating
      DC tolerance. The relative proportions of CD4(+) T cells, CD8(+) T cells, B
      cells, DCs, macrophages and regulatory T cells, and T-helper polarisation were
      unchanged by treatment with Pam3CSK(4)+DA-1229. CONCLUSIONS/INTERPRETATION: These
      data demonstrate that a combination of TLR2 tolerisation and DPP4 inhibition can
      reverse early-onset diabetes in NOD mice.

PMID- 23011353
TI  - Effect of a common variant of the PCSK2 gene on reduced insulin secretion.
AB  - AIM/HYPOTHESIS: Individuals at risk of developing type 2 diabetes show a
      progressive decline in insulin secretion and increased insulin resistance over
      time. However, inability of the beta cells to compensate for the increased
      insulin resistance represents a key defect leading to overt type 2 diabetes. The
      aims of the present study were to replicate the association between genetic
      variants of the PCSK2 gene and insulin secretion, and to explore the effect on
      risk of type 2 diabetes. METHODS: Replication of PCSK2 variants against insulin
      secretion included 7,682 non-diabetic Scandinavian individuals. Insulin secretion
      was measured as the corrected insulin response or disposition index, i.e. insulin
      secretion adjusted for the degree of insulin resistance. Risk of type 2 diabetes
      was studied in 28,287 Scandinavian individuals. RESULTS: The C-allele of PCSK2
      rs2208203 was associated with reduced insulin secretion measured as the corrected
      insulin response (n = 8,151; beta = -0.112, p = 1.3 * 10(-6)) as well as
      disposition index (n = 8,078, beta = -0.128, p = 1.6 * 10(-7)). The variant was
      also associated with lower fasting glucagon levels (beta = -0.084, p = 0.005) in
      non-diabetic individuals with a fasting plasma glucose of over 5.5 mmol/l. In
      human pancreatic islets, PCSK2 expression correlated negatively with HbA(1c) (n =
      133, r = -0.196, p = 0.038), and showed a tendency to be lower in hyperglycaemic
      (HbA(1c) >=6.0% or type 2 diabetes; n = 47, p = 0.13) than normoglycaemic
      (HbA(1c) >6.0%; n = 66) donors. The presence of the PCSK2 rs2208203 risk allele
      did not influence gene expression, nor did it show an apparent risk in terms of
      type 2 diabetes. CONCLUSIONS/INTERPRETATION: A variant of the PCSK2 gene was
      associated with reduced glucose-stimulated insulin secretion, but also with lower
      glucagon levels, which could potentially counteract the effects of decreased
      insulin secretion on the risk of type 2 diabetes.

PMID- 23011354
TI  - In vitro scan for enhancers at the TCF7L2 locus.
AB  - AIMS/HYPOTHESIS: Recent functional characterisations of genome-wide association
      study (GWAS) loci suggest that cis-regulatory variation may be a common paradigm
      for complex disease susceptibility. Several studies point to a similar mechanism
      at the transcription factor 7-like 2 (TCF7L2) GWAS locus for type 2 diabetes. To
      address this possibility, we carried out an in vitro scan of this diabetes
      associated locus to fine-map cis-regulatory sequences within this genomic
      interval. METHODS: A systematic cell-based enhancer strategy was employed to
      interrogate all sequences within the 92 kb type-2-diabetes-association interval
      for cis-regulatory activity in a panel of cell lines (HCT-116, Neuro-2a, C2C12,
      U2OS, MIN6 and HepG2). We further evaluated chromatin state at a subset of these
      regions in HCT-116 and U2OS cells and examined allelic-specific enhancer
      properties at the type-2-diabetes-associated single nucleotide polymorphism (SNP)
      rs7903146. RESULTS: In total, we assigned cis-regulatory activity to
      approximately 30% (9/28) of constructs tested. Notably, a subset of enhancers was
      active across multiple cell lines and overlapped with key epigenetic markers
      suggestive of cis-regulatory sequences. We further replicated the allelic
      specific properties for SNP rs7903146 in pancreatic beta cells and additionally
      demonstrate identical allelic-specific enhancer effects in other cell lines.
      CONCLUSIONS: These results provide a detailed map of cis-regulatory elements
      within the TCF7L2 GWAS locus and support the hypothesis of cis-regulatory
      variation leading to type 2 diabetes predisposition. The detection of allelic
      specific effects for SNP rs7903146 in multiple cell lines further alludes to the
      likelihood of a peripheral defect in disease aetiology.

PMID- 23011355
TI  - Fertility in people with childhood-onset type 1 diabetes.
AB  - AIMS/HYPOTHESIS: To assess the number of live births in a population-based,
      retrospective cohort of women and men with childhood-onset type 1 diabetes, and
      matched controls. METHODS: The reproductive histories of people in a Finnish
      cohort of 2,307 women and 2,819 men with type 1 diabetes and two matched controls
      (for each case) were obtained from National Population Register data. All persons
      with diabetes were diagnosed with the disease in 1965-1979 at the age of 17 or
      under. A proportional hazards model was used to model the association between the
      rate of live births as a function of the age of an individual and the observed
      covariates (sex and age at onset of diabetes). RESULTS: Both women and men with
      diabetes had a smaller number of live births than the controls; the HR of having
      a first child for diabetic women compared with controls was 0.66 (95% CI 0.62,
      0.71) and for men was 0.77 (95% CI 0.72, 0.83). In women, a birth cohort effect
      was detected; in more recent birth cohorts, the difference between diabetic women
      and controls as regards having children was significantly smaller than in earlier
      cohorts. Later age at onset of diabetes was associated with a higher rate of
      having a first child among men (p = 0.04) and having a second live birth among
      women (p = 0.002). CONCLUSIONS/INTERPRETATION: Type 1 diabetes affects the number
      of live births in both women and men. The age at onset of diabetes is associated
      with the pattern of reproduction in both diabetic women and men.

PMID- 23011356
TI  - Salinity of incubation media influences embryonic development of a freshwater
      turtle.
AB  - Variations in water potential have marked effects on aspects of embryological
      development in reptiles. Therefore variation in the salinity of the incubation
      environment is likely to have significant consequences on the early life stage.
      The combination of an extended incubation period, coupled with the real threat of
      soil salinisation within their range makes Chelodina expansa an ideal model to
      assess the influence of salinity on turtle embryology. We quantified the
      influence of salt on the development of C. expansa hatchlings in four substrate
      treatments varying in salinity. Embryos incubated in higher salinities had 39 %
      less survival than those incubated in substrates with freshwater. Hatchlings that
      emerged from eggs in saline treatments were smaller with higher concentrations of
      plasma sodium, chloride, urea, and potassium. The physiological effects of
      salinity mirror those of turtles incubated in drier media with low water
      potential. Salinisation of river banks has the potential to reduce hatching
      success and fitness of nesting reptiles.

PMID- 23011357
TI  - The effect of methotrexate on improving serological abnormalities of patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: This was an open-labeled, prospective, control study to determine the
      efficacy of methotrexate (MTX) for improving serological abnormalities in
      patients with systemic lupus erythematosus (SLE). METHODS: Thirty patients with a
      low serum complement and/or high anti-double-stranded DNA (dsDNA) antibody levels
      during a prednisolone taper received MTX orally at a dose of 7.5 mg/week over 12
      18 months (MTX group). Eighteen SLE patients were selected as controls (control
      group). At the time of entrance into the study, all patients were receiving <15
      mg/day of prednisolone. The C3, C4, and immunoglobulin (Ig)G, IgA, and IgM levels
      were measured using a turbidimetric immunoassay. The anti-dsDNA antibody level
      was measured using the Farr assay. RESULTS: Significant increases in C3 and C4
      levels and significant decreases in anti-dsDNA antibody, IgG, IgA, and IgM levels
      from baseline were observed for 3-18 months after the trial in the MTX group but
      not in the control group. At the end of the study, C3 and/or C4 levels in 96.7%
      of the MTX patients and 33.3% of the control patients were normalized or elevated
      (p = 0.0001), and anti-dsDNA antibody levels were normalized or lowered in 24 of
      the 26 MTX patients (92.3%) and in 50.0% of the control patients (p = 0.0022). In
      addition, a significant reduction in SLE Disease Activity Index (SLEDAI) score
      and a prednisolone-sparing effect were observed for the MTX group but not the
      control group. A significant increase in mean corpuscular volume of red blood
      cells, which is indicative of an anti-folic-acid metabolic disorder induced by
      MTX, was observed only for patients in the MTX group. Five patients (16.7%)
      discontinued MTX treatment because of disease flare, and another three (10.0%)
      discontinued due to treatment side effects. CONCLUSION: MTX appears to be
      effective for improving serological abnormalities frequently observed before
      disease flares in SLE patients on a prednisolone taper.

PMID- 23011358
TI  - A phase 3 randomized, double-blind, multicenter comparative study evaluating the
      effect of etanercept versus methotrexate on radiographic outcomes, disease
      activity, and safety in Japanese subjects with active rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this phase 3, double-blind study was to compare the
      radiographic and clinical effects of etanercept (ETN) versus methotrexate (MTX)
      over 52 weeks in Japanese subjects with active rheumatoid arthritis. METHODS: The
      study population comprised 550 subjects with inadequate response to >=1 disease
      modifying anti-rheumatic drugs who were randomized to treatment groups of ETN 25
      mg twice weekly (BIW; n = 182), ETN 10 mg BIW (n = 192), or MTX (<=8.0 mg/week; n
      = 176). RESULTS: Of the 550 subjects initially enrolled in the three treatment
      groups, 21.6% discontinued the study; a significantly higher proportion of those
      who withdrew from the study due to lack of efficacy were in the MTX (21.6%) group
      compared with the ETN 25 mg (3.3%) and ETN 10 mg (6.8%) groups (P < 0.001). Mean
      change from baseline in the modified total Sharp score at week 52 (primary
      endpoint) was significantly lower in the ETN 25 mg [3.33; standard error (SE),
      0.73] and ETN 10 mg (5.19; SE 0.93) groups than in the MTX group (9.82; SE 1.16;
      P < 0.0001 vs. either ETN group). Compared with subjects receiving MTX,
      significantly higher percentages of subjects treated with ETN 25 and 10 mg
      achieved American College of Rheumatology (ACR) ACR20 and ACR50 response rates at
      all time points (P < 0.01). ETN was well-tolerated, with no unexpected safety
      findings. CONCLUSIONS: ETN 25 mg BIW and ETN 10 mg BIW slowed radiographic
      progression and improved clinical outcomes more effectively than MTX in this
      Japanese population.

PMID- 23011360
TI  - [One-step rhinootosurgery. Clinical, economic and social aspects].
AB  - The objective of this work was to estimate from the clinical, economic, and
      social standpoints the efficacy of medical aid provided to the patients with
      chronic suppurative otitis media (CSOM) and concomitant pathology of the nasal
      cavity by means of the one-step surgical intervention. The study included a total
      of 208 patients presenting with CSOM of whom 108 ones were treated by the
      traditional multistage method and the remaining 108 by simultaneous
      rhinootosurgery. The latter approach was shown to be much more efficacious in
      terms of clinical, economic, and social considerations.

PMID- 23011361
TI  - [The substantiation of the approach for endoscopic surgery of nasal liquorrhea].
AB  - The objective of the present study was to develop a rationale for the approach to
      be employed in endoscopic surgery of nasal liquorrhea. A total of 69 patients
      presenting with this condition were available for the observation. Traumatic
      liquorrhea accounted for 80% of the cases, iatrogenic liquorrhea for 10%,
      liquorrhea associated with malformations for 5%, and spontaneous liquorrhea for
      5% of the cases. The diagnostic algorithms elaborated for the identification of
      liquor cartilages were used to develop the criteria for the choice of the
      operative approach. A total of 69 surgical interventions were performed including
      54 transnasal, 20 transethmoidal, 29 transsphenoidal, 5 endonasal, and 15
      transcranial operations. The liquor fistulas were closed using tissue fragments
      and artificial materials, viz. muscles, broad fascia of thigh, periosteum and
      cartilage of the nasal septum, the mucous membrane from the nasal cavity,
      TachoComb plates, hemostatic sponge, fibrin-thrombin glue, bone crumbs, elements
      of bone marrow, and stem cells. The study has demonstrated the advantages of
      transnasal surgical treatment of liquor fistulas. The principles of postoperative
      care for the patients have been developed.

PMID- 23011362
TI  - [The substantiation of the rational otorhinolaryngological strategy for the
      treatment of the severe form of a combined head injury with the damage to the
      nasal sinuses].
AB  - The objective of the present work was to substantiate the rational
      otorhinolaryngological strategy for the treatment of the severe form of combined
      head injuries with the damage to the nasal sinuses. The theoretical support of
      the study was provided by the use of such methods as analysis and synthesis,
      generalization and comparison. The practical methods included the general
      clinical studies, tests for the functional state of the intranasal mucous
      membrane, evaluation of motor activity of ciliated epithelium and microbiological
      techniques. A total of 42 patients with a combined head injury were examined.
      Congestive processes in the system of nasal sinuses were shown to develop as
      early as the onset of artificial lung ventilation even in the absence of an
      injury to the paranasal sinuses. The functional activity of ciliated epithelium
      was compromised since the first day of artificial lung ventilation and continued
      to worsen with time. The restoration of the nasal breathing promoted the creation
      of conditions for the recovery of the functional activity of ciliated epithelium.
      The secondary site of infection in the nasal sinuses formed on days 3-5.

PMID- 23011363
TI  - [Otoneurology (definition, brief historical note, classification)].
AB  - The authors consider otoneurology to be an integral constituent part of general
      otorhinolaryngology. They propose its definition, present a brief historical
      sketch of this scientific discipline, and describe the principles of
      classification of the pathological conditions encompassed by this branch of
      general otorhinolaryngology.

PMID- 23011364
TI  - [Possibilities for the application of the computed videooculographic technique in
      the clinical practice for the treatment of the patients presenting with
      vestibular disorders].
AB  - The objective of the present study was to carry out clinical examination of the
      patients presenting with peripheral total cochleovestibular syndrome combined
      with vertebrobasiliar insufficiency before (in the phase of exacerbation),
      during, and after the conservative treatment that consisted of a course of
      traditional drug therapy. A relatively new diagnostic method of computed
      videooculography was applied. The 316 patients with the aforementioned combined
      pathology who received conservative pharmacotherapy were available for the
      dynamic follow-up. It was shown that computed videooculography provides a highly
      sensitive diagnostic tool detecting even the minimal changes in the
      responsiveness of the vestibular analyzer. The introduction of the computed
      videooculographic technique in the program of medical examination makes it
      possible to considerably increase the accuracy of diagnostics, optimize
      differential diagnostics and management of the patients suffering from vestibular
      disorders.

PMID- 23011365
TI  - [The importance of estimation of the quality of life in the patients with
      vestibular disorders].
AB  - The objective of the present study was to develop and introduce into clinical
      practice the method for the estimation of the quality of life in the patients
      with vestibular disorders as a measure of the efficacy of their treatment and as
      a diagnostic criterion to be used in regular medical examinations. Sixty eight
      patients presenting with total cochleovestibular syndrome were interviewed for
      the elucidation their quality of life using the questionnaire specially developed
      by the researchers of the Department of Otorhinolaryngology, I.I. Mechnikov Sankt
      Peterburg State Medical Academy, in accordance with the internationally accepted
      guidelines. Special attention was given to the determination of significant
      changes indicative of the severity of the pathological process at different
      periods of time. It is concluded that the questionnaire designed to estimate the
      quality of life of the patients provides an efficacious diagnostic tool for the
      estimation of the health status of the subjects with vestibular dysfunction that
      reflects the patient's self-assessment. Such information is impossible to obtain
      by objective diagnostic methods, such as computed videooculography.

PMID- 23011366
TI  - [The pathogenetic approach to the development of tools and methods for the
      improvement of statokinetic stability in the operators of aerospace systems].
AB  - The objective of the present study was to estimate the efficacy of the tools and
      methods for the optimization of the activity of the central nervous system (CNS)
      and analyzers involved in the maintenance of the statokinetic (SK) stability in
      man. To this effect, we evaluated the outcome of bemitil treatment during 10 days
      with and without A.I. Yarotsky test and the influence of these procedures on the
      pathophysiological characteristics of selected elements of the work of operators
      of aerospace systems. Based on the data obtained in the study, the tools and
      methods have been developed that allow the efficacy and quality of certain
      aspects of the operators' activity to be improved, viz. general working capacity
      under conditions requiring enhanced statokinetic stability, self-confidence,
      emotional and somatic comfort.

PMID- 23011367
TI  - [The role of genetic mutations in the patents with the acquired forms of
      sensorineural impairment of hearing].
AB  - The objective of the present work was to study the role of GST genes in
      pathogenesis of various neurodegenerative conditions with special reference to
      sensorineural impairment of hearing. The DNA samples obtained from 200 subjects
      were available for the investigation; 109 of them were the patients hospitalized
      in the otorhinolaryngologcal clinic of S.M. Kirov Military Medical Academy for
      the treatment of uni- or bilateral impairment of hearing. The polymerase chain
      reaction with subsequent specific restriction endonuclease analysis was used to
      study genetic mutations. The analysis was focused on the 35delG mutation in the
      GJB2 gene (DFNB1). In addition, the MTRNR1 (12S rRNA) and MTTS1 (serine tRNA)
      genes in the patients with acquired sensorineural impairment of hearing were
      subjected to analysis. Polymorphism of the second detoxication phase gene (GSTM1)
      was investigated. It was shown that mitochondrial genes MTRNR1 and MTTS1
      contribute to the development of acquired sensorineural impairment of hearing.
      The frequency of heterozygous 35delG mutations of the GJB2 (DFNB1) gene among the
      subjects with impaired hearing does not significantly differ from its prevalence
      in the general population. The allelic mutation of the GSTM1 gene is believed to
      be a predisposing factor for the development of sensorineural impairment of
      hearing under the action of intoxication and/or infections.

PMID- 23011368
TI  - [The stabilometric evaluation of resistance to motion sickness in man].
AB  - This work was designed to develop a mathematical model based on the results of
      computed stabilometry in the subjects differing in the degree of resistance to
      motion sickness. The model is designed for the purpose of instant diagnostics in
      the course of occupational selection. Stabilometric characteristics of 61 men
      aged from18 to 24 years were compared with those obtained by the method of
      continuous cumulation of Coriolis accelerations. The accuracy of diagnostics with
      the use of stabilometry was estimated at 93.2%. It is concluded that computed
      stabilometry provides an efficacious tool for the assessment of sensitivity to
      motion sickness for the purpose of professional selection.

PMID- 23011369
TI  - [The efficacy of medical care following modified rhinosurgical interventions].
AB  - The objective of the present study was to evaluate the efficacy of medical aid
      after modified rhinosurgical interventions with the use of the methods for the
      objective assessment of the normalization of the nasal function and the patients'
      quality of life during the treatment. A total of 38 patients presenting with
      deviation of the nasal septum and persistent disturbances of the nasal breathing
      were examined and treated to estimate the quality of the medical aid following
      modified rhinosurgical interventions. The study has demonstrated the high quality
      of medical care for the patients undergoing modified rhinosurgical interventions
      which is the leading criterion for the treatment of the subjects suffering
      diseases of the nasal cavity.

PMID- 23011370
TI  - [Epidemiology and prophylaxis of ENT diseases in the cadets of the Nakhimov Naval
      School].
AB  - The objective of the present study was to determine the prevalence of
      otorhinolaryngological morbidity among the cadets of the Nakhimov Naval School
      and propose the effective measures for its reduction and prevention. A total of
      335 children at the age from 11 to 17 years were available for the examination.
      The analysis of otorhinolaryngological morbidity during September and October
      2011 revealed the high frequency of acute respiratory diseases (46 cases) and
      maxillary sinus symptoms (12 cases). The newly recruited children accounted for
      40% of the affected patients. The results of the screening carried out in the
      military educational institution suggest the necessity of improvement of the
      quality of primary medical screening, timely diagnostics and correction of
      pathological conditions. They can be used to formulate the long-range objectives
      for the improvement of individual recommendations for the medical observation of
      the cadets presenting with chronic ENT diseases.

PMID- 23011371
TI  - [The magnitude and the structure of ENT sanitary losses in modern local armed
      conflicts].
AB  - The objective of the present study was to estimate the magnitude and the
      structure of ENT losses in modern local armed conflicts. We have considered
      characteristics of battle injuries inflicted in modern wars based on the
      materials collected during the armed conflicts in the Caucasus during 1999-2002
      and stored in the Military Medical Museum (MMM) of the Russian Defense Ministry.
      A total of 5608 case records of the surgical treatment of mechanical injuries
      were analysed including 4002 gunshot wounds and 1606 closed injuries
      (contusions). ENT and neck wounds were the main and concomitant injuries in 102
      and 107 subjects respectively who accounted for 2.5% and 2.7% of all the wounded
      servicemen. Fifty five (3.93%) and 21 (1.3%) of the 1606 subjects had a closed
      ENT and neck wound as the leading and concomitant injury, respectively. According
      to the materials collected in MMM, ENT contusion was the main injury in 111 (25%)
      of the 410 servicemen who had received contused wounds in the armed conflict of
      1999-2002.

PMID- 23011372
TI  - [The currently available possibilities for fixation of many-layer transplants in
      myringoplasty].
AB  - The objective of the present study was to improve the quality and efficacy of the
      surgical treatment of chronic otitis media including the plastic correction of
      total and subtotal tympanic defects by fixing a many-layer chondro-perichondrial
      autograft with the use of a latex tissue glue. Twenty seven patients presenting
      with total and subtotal defects of the tympanic membrane underwent surgical
      intervention in the lateral position. The multilayer transplants composed of a
      thinned cartilage, fascia, and transposed circular cutaneous graft on the feeding
      pedicle were fixed using the latex tissue glue. The morphological and functional
      results of the treatment were estimated one year after surgery. It was shown that
      the use of the latex tissue glue for the fixation of many-layer autografts during
      myringoplasty made it possible to decrease the duration of the hospital stay of
      the patients, reduce to a minimum manifestations of negative subjective feelings,
      and ensure the reliable clinico-morphological and functional outcome of the
      treatment.

PMID- 23011373
TI  - [The correction of Eustachiantube dysfunction after microscopic rhinological
      surgical interventions by prolonged transtubal drainage].
AB  - The objective of the present study was to analyse the results of he treatment of
      Eustachian tube dysfunction by means of prolonged transtubal drainage of the tube
      lumen using a polyethylene catheter introduced immediately after the completion
      of the rhinosurgical intervention for the targeted delivery of pharmaceutical
      products. Eighty four patients with Eustachian tube dysfunction and impairment of
      hearing had a thin catheter introduced in the tube lumen for 7-14 days after
      various rhinosurgical interventions. We estimated the efficacy of the local
      treatment following rhinosurgery with the subsequent prolonged administration of
      pharmaceutical products through the intratubal drainage system. It is concluded
      that the introduction of a thin polyethylene drainage in the Eustachian tube
      lumen immediately after the rhinosurgical intervention combined with subsequent
      prolonged local pharmacotherapy make it possible to achieve the long-term
      recovery of the tube function in 80% of the patients.

PMID- 23011374
TI  - [The application of computed stabilometry for the diagnostics of vestibular
      disorders following stapedoplasty and for the estimation of the functional status
      in man].
AB  - The present work was designed to estimate changes in the quality of the
      equilibrium function (QEF) and dynamic stabilization indices (DSI) of the
      vertical position of the body in comparison with the traditional stabilometric
      characteristics (the length and the area of statokinesigram, mean radius of body
      deviation, average linear centre of foot pressure displacement velocity). The
      computed stabilometric technique was used to study the equilibrium function in
      the patients (n=133) presenting with otorhinolaryngological problems and
      requiring the surgical treatment. It was shown that selected stabilometric
      characteristics (such as QEF and DSI) may be useful for control of the efficacy
      of the treatment of surgical patients; moreover, they can be applied to the
      evaluation of dynamics of the patients' health status during the postoperative
      period.

PMID- 23011375
TI  - [The experience with the rehabilitation of the patients with paralytic laryngeal
      stenosis].
AB  - This paper is designed to familiarize otorhinilaryngologists with the practical
      methods applied in the surgical rehabilitation of the patients presenting with
      paralytic laryngeal stenosis. We report the results of the treatment of 13
      patients with this pathology differing in age and duration of the disease
      following strumectomy. Paralytic laryngeal stenosis was eliminated in 11 of the
      13 patients. The favourable prognosis was strongly dependent on the time interval
      between the development of laryngeal paralysis and the surgical intervention. The
      total duration of the treatment of different patients varied from 8.5 months to
      1.5 years because some of them required corrective surgery.

PMID- 23011376
TI  - [Estimation of the quality of medical aid in otosurgery].
AB  - The objective of the present work was to develop a system of assessment of the
      efficacy and quality of the surgical treatment of the patients presenting with
      chronic otitis media as a method for the improvement of surgical aid to the
      subjects with this condition. The system of evaluation of the quality of medical
      aid to the patients with chronic suppurative otitis media was based on the
      criteria for the assessment of the efficacy and quality of the surgical treatment
      by both the attending physician and the patient. The proposed method makes it
      possible to standardize the approaches to the estimation of the quality of
      medical aid, objectivate its characteristics, and carry out the comparative
      analysis of the efficacy and quality of the new methods for the surgical
      treatment of the patients with chronic suppurative otitis media.

PMID- 23011377
TI  - [The acceleration of remission after exacerbation of chronic suppurative otitis
      media following functional-reconstructive operations on the middle ear].
AB  - This study had the objective to enhance the efficacy of the surgical treatment of
      the patients presenting with chronic suppurative otitis media by means of
      reduction of the time needed to achieve persistent remission of the disease in
      the framework of a complex of therapeutic and rehabilitative measures making
      possible the surgical intervention on the middle ear regardless of the activity
      of the inflammatory process and its severity. Sixty five patients with chronic
      suppurative otitis media were examined and treated to estimate the clinical
      efficiency of the proposed complex of therapeutic and rehabilitative measures. It
      is maintained that this complex allows to achieve the positive results of
      reconstructive and restorative surgery without waiting for the development of
      long-term remission.

PMID- 23011378
TI  - [The treatment of chronic polypous rhinosinusitis in the postoperative period
      with low doses of clarithromycin].
AB  - The aim of this work was to study efficacy and safety of long-term low-dose
      clarithromycin therapy of chronic polypous rhinosinusitis during 6 months after
      endoscopic polyposinusotomy. 112 patients aged 25-65 yr were randomized in groups
      7 days after surgery. Those in group 1 (n=66) received topic corticosteroid
      treatment in combination with clarithromycin (250 mg/day for 3 mo). The use of
      clarithromycin significantly decreased the number of clinical symptoms and
      improved quality of life. CT examination showed significant reduction in the
      frequency of relapses, episodes of acute respiratory viral infections, and their
      bacterial complications. All these effects persisted for 3 mo after withdrawal of
      clarithromycin.

PMID- 23011379
TI  - [Influence of sycloferon on the sytokine blood profile and production of
      proinflammatory sytokines in the cultures of mononucleares of peripheral blood of
      the patients with chronic tonsillitis].
AB  - The 88 patients with chronic tonsillitis (CT) was investigated. The 46 patients
      (basic group) got the modern immunoactive preparation cycloferon and 42 patients
      (comparison group) - only the generally accepted therapy. During immunological
      researches on a background clinical manifestation of ST the increase
      proinflammatory cytokines (CK) (TNFalpha, IL-1Beta) in the serum, and also
      increase the level of spontaneous products of these CK in the cultures
      mononucleares of periferal blood was detected. At general accepted treatment took
      place increase level proinflammatory CK at serum on background decline stimulated
      product of CK at mononucleares cultures. Arplication of cycloferon at the
      treatment of CT provided to normalization cytokines profile of the blood and
      production of CK in the cultures mononucleares.

PMID- 23011380
TI  - [Dysfunction of the Eustachian tube and endothelial dysfunction: the present view
      of the problem (Part 1)].
AB  - This paper is focused on the topical otorhinolaryngological problem of Eustachian
      tube dysfunction, a pathological condition preceding or accompanying exudative
      otitis media. Based on the results of modern fundamental research, the author
      considers for the first time the role of endotoxins of Gram-negative
      microorganisms and endothelial dysfunction in etiology and pathogenesis of tubal
      disorders, exudative otitis media, and the related complications of sensorineural
      impairment of hearing.

PMID- 23011381
TI  - Dynamics of a stochastic spatially extended system predicted by comparing
      deterministic and stochastic attractors of the corresponding birth-death process.
AB  - Living cells may be considered as biochemical reactors of multiple steady states.
      Transitions between these states are enabled by noise, or, in spatially extended
      systems, may occur due to the traveling wave propagation. We analyze a one
      dimensional bistable stochastic birth-death process by means of potential and
      temperature fields. The potential is defined by the deterministic limit of the
      process, while the temperature field is governed by noise. The stable steady
      state in which the potential has its global minimum defines the global
      deterministic attractor. For the stochastic system, in the low noise limit, the
      stationary probability distribution becomes unimodal, concentrated in one of two
      stable steady states, defined in this study as the global stochastic attractor.
      Interestingly, these two attractors may be located in different steady states.
      This observation suggests that the asymptotic behavior of spatially extended
      stochastic systems depends on the substrate diffusivity and size of the reactor.
      We confirmed this hypothesis within kinetic Monte Carlo simulations of a bistable
      reaction- diffusion model on the hexagonal lattice. In particular, we found that
      although the kinase-phosphatase system remains inactive in a small domain, the
      activatory traveling wave may propagate when a larger domain is considered.

PMID- 23011382
TI  - Default mode network activity and white matter integrity in healthy middle-aged
      ApoE4 carriers.
AB  - Alzheimer's disease (AD) is most commonly detected during old age, but the
      underlying neuropathologic changes likely appear decades earlier, especially
      among patients possessing genetic risk factors, such as the isoform E4 of the
      apolipoprotein E (ApoE4). In this study, we used magnetic resonance imaging (MRI)
      to assess default mode network (DMN) connectivity in 22 ApoE4 non-carriers and 14
      matched ApoE4 carriers as well as white matter fractional anisotropy (FA) in 15
      ApoE4 non-carriers and 11 demographically matched ApoE4 carriers. Cognitive tests
      were also administered. All of the participants were middle-aged adults. The
      analysis revealed no cognitive or white matter FA differences between carriers
      and non-carriers. However, in DMN regions previously implicated in AD, we did
      detect decreased functional connectivity. Our findings suggest that functional
      MRI abnormalities may be detectable well before cognitive decline or white matter
      changes among individuals at increased genetic risk for AD.

PMID- 23011384
TI  - Tetrametallic molecular catalysts for photochemical water oxidation.
AB  - Among molecular water oxidation catalysts (WOCs), those featuring a reactive set
      of four multi-redox transition metals can leverage an extraordinary interplay of
      electronic and structural properties. These are of particular interest, owing to
      their close structural, and possibly functional, relationship to the oxygen
      evolving complex of natural photosynthesis. In this review, special attention is
      given to two classes of tetrametallic molecular WOCs: (i) M(4)O(4) cubane-type
      structures stabilized by simple organic ligands, and (ii) systems in which a
      tetranuclear metal core is stabilized by coordination of two polyoxometalate
      (POM) ligands. Recent work in this rapidly evolving field is reviewed, with
      particular emphasis on photocatalytic aspects. Special attention is given to
      studies addressing the mechanistic complexity of these systems, sometimes
      overlooked in the rush for oxygen evolving performance. The complementary role of
      molecular WOCs and their relationship with bulk oxides and heterogeneous
      catalysis are discussed.

PMID- 23011383
TI  - Neuropsychological variability, symptoms, and brain imaging in chronic
      schizophrenia.
AB  - We examined variability in performance on widely-used neuropsychological Wechsler
      tests of intelligence and memory in a large sample of persons with chronic
      schizophrenia, a subset of whom had also undergone prior studies of magnetic
      resonance imaging (MRI) of the orbital frontal cortex (OFC) gray matter and
      diffusion tensor imaging (DTI) of the cingulum bundle (CB) and the uncinate
      fasiculus (UF) white matter. In comparison to controls, persons with
      schizophrenia showed lower scores across neuropsychological tests, with most
      pronounced drops in processing speed and immediate memory, in relation to oral
      reading. For patients, greater declines in intelligence and memory each
      correlated with reduced CB white matter fractional anisotropy and reduced OFC
      gray matter, respectively. However, only memory decline correlated with severity
      of negative symptoms. Taken together, these data raise the intriguing question as
      to whether communication and motivational deficits expressed in negative symptoms
      may contribute to the relationship of auditory memory decline and OFC volume
      observed in this patient sample.

PMID- 23011385
TI  - Experimental and theoretical study of the [3 + 2] cycloaddition of carbonyl
      ylides with alkynes.
AB  - The [3 + 2] cycloaddition reaction between carbonyl ylides generated from
      epoxides and alkynes (phenylacetylene, methyl propiolate, methyl but-2-ynoate and
      methyl 3-phenylpropiolate) to give substituted 2,5-dihydrofurans was
      investigated. The effect of indium(III) chloride on the outcome of the reaction
      was studied in the case of phenylacetylene and methyl propiolate. The thermal
      reaction between the carbonyl ylide coming from 2,2-dicyano-3-phenyloxirane and
      both methyl propiolate and methyl but-2-ynoate was theoretically investigated
      using DFT methods in order to explain the reactivity and regioselectivity
      observed.

PMID- 23011386
TI  - Implantation of a cardiac resynchronization therapy defibrillator in a patient
      with bilateral deep brain stimulator: feasibility and technique.
AB  - Uncommonly, a patient with a NeuroStimulator Device (NSD) for a neurologic
      indication requires a cardiovascular implantable electronic device (CIED) for a
      cardiac indication. Typically in those with a unilateral pectoral NSD, the
      contralateral pectoral space is used for CIED implantation; however, in very rare
      occasions the patient has bilateral pectoral NSDs which makes subsequent
      implantation of a CIED challenging both because of placement and device
      interaction. Herein, we introduce the case of a 68-year-old gentleman with
      bilateral pectoral deep brain stimulators for Parkinsonism who received cardiac
      resynchronization therapy-defibrillator (CRT-D) for advanced heart failure. The
      CRT-D generator was implanted in the abdomen and the CRT-D leads were placed
      through a minimally invasive epicardial approach. Both devices were tested
      without any evidence of device interaction.

PMID- 23011387
TI  - Atrial conduction time and atrial mechanical function in patients with impaired
      fasting glucose.
AB  - BACKGROUND: Prolonging atrial conduction time, as measured by tissue Doppler
      imaging (TDI), is an independent predictor of new onset or recurrent atrial
      fibrillation (AF). We investigated atrial conduction time and cardiac mechanical
      function in patients with impaired fasting glucose (IFG) using echocardiography.
      METHODS: Thirty patients with IFG (19 males and 11 females; age, 46.9 +/- 9.5
      years) and 30 control subjects (18 males and 12 females; age, 46.7 +/- 8.2 years)
      were included. Atrial conduction time was determined from the lateral mitral
      annulus (PA lateral), septal mitral annulus (PA septal), and lateral tricuspid
      annulus (PA tricuspid) by TDI. Inter- and intra-atrial electromechanical delays
      (EMDs) were calculated. Left atrial (LA) volumes were determined according to the
      biplane area-length method. LA mechanical function parameters were calculated.
      RESULTS: LA passive emptying volume and LA passive emptying fraction decreased
      significantly in patients with IFG as compared with control subjects (p < 0.001
      and p < 0.001, respectively). PA lateral and PA septal durations were
      significantly higher in patients with IFG than in the control group. However, no
      difference in PA tricuspid duration was observed between the two groups. Inter-
      and intra-atrial EMDs were significantly higher in patients with IFG as compared
      with the control subjects (median [interquartile range], 34.0 [17.0] vs. 17.0
      [4.0], p < 0.001 and 15.0 [8.5] vs. 7.5 [2.0], p < 0.001, respectively). Positive
      correlations were detected between both inter- and intra-atrial EMD and glucose
      levels (r = 0.76, p < 0.001 and r = 0.68, p < 0.001, respectively). Additionally,
      a multiple linear regression analysis revealed that glucose levels were
      independently associated with inter-atrial EMD (beta = 0.753, p < 0.001).
      CONCLUSION: We showed that IFG was associated with inter- and intra-atrial EMD.
      Our findings suggest that IFG is an etiological factor for the development of AF.

PMID- 23011388
TI  - High risks for adverse outcomes after gastric bypass surgery following failed
      gastric banding: a population-based trend analysis of the United States.
AB  - OBJECTIVES: The objectives of this investigation were to (1) compare short-term
      outcomes for patients undergoing primary gastric bypass surgery with those who
      had gastric bypass procedures performed as a rescue procedure after failed
      gastric banding and (2) study trends in the frequency of reoperations between
      2005 and 2008 for patients who had prior gastric banding. BACKGROUND: The use of
      gastric banding to treat obesity has increased drastically in the United States.
      However, the frequency of reoperations related to gastric banding and associated
      short-term outcomes are unknown. METHODS: The Nationwide Inpatient Sample from
      2005 to 2008 was used for this population-based study. Descriptive statistics as
      well as unadjusted and risk-adjusted generalized linear models were performed to
      assess adverse short-term outcomes. RESULTS: A total of 66,303 patients were
      included in the analysis, 63,171 (95.3%) underwent a primary gastric bypass
      procedure and 3132 patients (4.7%) underwent a gastric band-related reoperation.
      Patients undergoing a gastric bypass procedure concomitant with a band-related
      reoperation had more intraoperative complications [risk-adjusted odds ratio (OR):
      2.3, P = 0.002] and postoperative complications (risk-adjusted OR: 8.0, P <
      0.001), were at higher risk of reoperations/reinterventions (risk-adjusted OR:
      6.0, P < 0.001), increased length of hospital stay (adjusted mean difference:
      0.89 days, P < 0.001), and higher hospital charges (adjusted mean difference:
      $13,257, P < 0.001). The number of gastric band-related reoperations increased
      from 579 in 2005 to 1132 in 2008 (196%). CONCLUSIONS: The number of reoperations
      after gastric banding is rapidly increasing in the United States. To our
      knowledge, this is the first population-based study providing strong evidence
      that patients undergoing gastric bypass procedure after failed gastric banding
      have more adverse outcomes than those undergoing gastric bypass alone. The broad
      indication for gastric banding should be reaffirmed for the US population.

PMID- 23011391
TI  - Sensitive point-of-care monitoring of HIV related DNA sequences with a personal
      glucometer.
AB  - The hybridizations between the HIV target DNA and the capture probes as well as
      the signal probes conjugated to the multi-invertase/nanoparticle composites lead
      to the conversion of sucrose to glucose, which is monitored by the personal
      glucometer and provides quantitative digital readings for point-of-care diagnosis
      of HIV DNA fragments.

PMID- 23011390
TI  - Wnt pathway activation predicts increased risk of tumor recurrence in patients
      with stage I nonsmall cell lung cancer.
AB  - OBJECTIVE: To determine the incidence of Wnt pathway activation in patients with
      stage I NSCLC and its influence on lung cancer recurrence. BACKGROUND: Despite
      resection, the 5-year recurrence with localized stage I nonsmall cell lung cancer
      (NSCLC) is 18.4%-24%. Aberrant Wnt signaling activation plays an important role
      in a wide variety of tumor types. However, there is not much known about the role
      the Wnt pathway plays in patients with stage I lung cancer. METHODS: Tumor and
      normal lung tissues from 55 patients following resection for stage I NSCLC were
      subjected to glutathione S-transferase (GST) E-cadherin pulldown and immunoblot
      analysis to assess levels of uncomplexed beta-catenin, a reliable measure of Wnt
      signaling activation. The beta-catenin gene was also screened for oncogenic
      mutations in tumors with activated Wnt signaling. Cancer recurrence rates were
      correlated in a blinded manner in patients with Wnt pathway-positive and 
      negative tumors. RESULTS: Tumors in 20 patients (36.4%) scored as Wnt positive,
      with only 1 exhibiting a beta-catenin oncogenic mutation. Patients with Wnt
      positive tumors experienced a significantly higher rate of overall cancer
      recurrence than those with Wnt-negative tumors (30.0% vs. 5.7%, P = 0.02), with
      25.0% exhibiting distal tumor recurrence compared with 2.9% in the Wnt-negative
      group (P = 0.02). CONCLUSIONS: Wnt pathway activation occurred in a substantial
      fraction of Stage I NSCLCs, which was rarely due to mutations. Moreover, Wnt
      pathway activation was associated with a significantly higher rate of tumor
      recurrence. These findings suggest that Wnt pathway activation reflects a more
      aggressive tumor phenotype and identifies patients who may benefit from more
      aggressive therapy in addition to resection.

PMID- 23011392
TI  - Cognitive neuroscience: selection through synchrony.

PMID- 23011393
TI  - Tbx1 genetically interacts with the transforming growth factor-beta/bone
      morphogenetic protein inhibitor Smad7 during great vessel remodeling.
AB  - RATIONALE: Growth and remodeling of the pharyngeal arch arteries are vital for
      the development of a mature great vessel system. Dysmorphogenesis of the fourth
      arch arteries can result in interruption of the aortic arch type B, typically
      found in DiGeorge syndrome. Tbx1 haploinsufficient embryos, which model DiGeorge
      syndrome, display fourth arch artery defects during formation of the vessels.
      Recovery from such defects is a documented yet unexplained phenotype in Tbx1
      haploinsufficiency. OBJECTIVE: To understand the nature of fourth arch artery
      growth recovery in Tbx1 haploinsufficiency and its underlying genetic control.
      METHODS AND RESULTS: We categorized vessel phenotypes of Tbx1 heterozygotes as
      hypoplastic or aplastic at the conclusion of pharyngeal artery formation and
      compared these against the frequency of vessel defects scored at the end of great
      vessel development. The frequency of hypoplastic vessels decreased during
      embryogenesis, whereas no reduction of vessel aplasia was seen, implying recovery
      is attributable to remodeling of hypoplastic vessels. We showed that Smad7, an
      inhibitory Smad within the transforming growth factor-beta pathway, is regulated
      by Tbx1, is required for arch artery remodeling, and genetically interacts with
      Tbx1 in this process. Tbx1 and Tbx1;Smad7 haploinsufficiency affected several
      remodeling processes; however, concurrent haploinsufficiency particularly
      impacted on the earliest stage of vascular smooth muscle cell vessel coverage and
      subsequent fibronectin deposition. Conditional reconstitution of Smad7 with a
      Tbx1Cre driver indicated that the interaction between the 2 genes is cell
      autonomous. CONCLUSIONS: Tbx1 acts upstream of Smad7 controlling vascular smooth
      muscle and extracellular matrix investment of the fourth arch artery.

PMID- 23011394
TI  - Loss of adenomatous poliposis coli-alpha3 integrin interaction promotes
      endothelial apoptosis in mice and humans.
AB  - RATIONALE: Pulmonary hypertension (PH) is characterized by progressive elevation
      in pulmonary pressure and loss of small pulmonary arteries. As bone morphogenetic
      proteins promote pulmonary angiogenesis by recruiting the Wnt/beta-catenin
      pathway, we proposed that beta-catenin activation could reduce loss and induce
      regeneration of small pulmonary arteries (PAs) and attenuate PH. OBJECTIVE: This
      study aims to establish the role of beta-catenin in protecting the pulmonary
      endothelium and stimulating compensatory angiogenesis after injury. METHODS AND
      RESULTS: To assess the impact of beta-catenin activation on chronic hypoxia
      induced PH, we used the adenomatous polyposis coli (Apc(Min/+)) mouse, where
      reduced APC causes constitutive beta-catenin elevation. Surprisingly, hypoxic
      Apc(Min/+) mice displayed greater PH and small PA loss compared with control
      C57Bl6J littermates. PA endothelial cells isolated from Apc(Min/+) demonstrated
      reduced survival and angiogenic responses along with a profound reduction in
      adhesion to laminin. The mechanism involved failure of APC to interact with the
      cytoplasmic domain of the alpha3 integrin, to stabilize focal adhesions and
      activate integrin-linked kinase-1 and phospho Akt. We found that PA endothelial
      cells from lungs of patients with idiopathic PH have reduced APC expression,
      decreased adhesion to laminin, and impaired vascular tube formation. These
      defects were corrected in the cultured cells by transfection of APC. CONCLUSIONS:
      We show that APC is integral to PA endothelial cells adhesion and survival and is
      reduced in PA endothelial cells from PH patient lungs. The data suggest that
      decreased APC may be a cause of increased risk or severity of PH in genetically
      susceptible individuals.

PMID- 23011395
TI  - Family network proportion and HIV risk among black men who have sex with men.
AB  - OBJECTIVES: Black men who have sex with men (BMSM) have the highest rates of HIV
      in the United States. Despite increased attention to social and sexual networks
      as a framework for biomedical intervention, the role of family in these networks
      and their relationship to HIV prevention have received limited attention.
      METHODS: A network sample (N = 380) of BMSM (n = 204) and their family members (n
      = 176) was generated through respondent-driven sampling of BMSM and elicitation
      of their personal networks. The proportion of personal network members who were
      family was calculated, and the weighted logistic regression was used to assess
      the relationship between this proportion and unprotected anal intercourse, sex
      drug use (SDU), and group sex (GS), as well as intravention efforts to discourage
      these risk behaviors among their MSM social networks. RESULTS: 45.3% of
      respondents listed at least 1 family member in their close personal network.
      Greater family network proportion (having 2 or more family members in the close
      network) was associated with less SDU [adjusted odds ratio (AOR) 0.38, 95% CI:
      0.17 to 0.87] and participation in GS (AOR 0.25, 95% CI: 0.10 to 0.67). For
      intravention, BMSM with greater family proportion were more likely to discourage
      GS (AOR 3.83, 95% CI: 1.56 to 9.43) and SDU (AOR 2.18, 95% CI: 1.35 to 3.54)
      among their MSM friend network. Moreover, increased male family network
      proportion was associated with lower HIV risk and greater intravention than
      increased female network proportion. CONCLUSIONS: Nearly half of BMSM have a
      close family member with whom they share personal information. Combination
      prevention interventions might be made more potent if this often overlooked
      component of personal networks was incorporated.

PMID- 23011396
TI  - Simultaneous population pharmacokinetic modelling of atazanavir and ritonavir in
      HIV-infected adults and assessment of different dose reduction strategies.
AB  - OBJECTIVES: The objective of this study was to develop a simultaneous population
      pharmacokinetic (PK) model to describe atazanavir/ritonavir (ATV/RTV) PK (300/100
      mg) and to assess the effect of RTV dose reduction on ATV PK. Simulations of ATV
      concentration-time profiles were performed at doses of ATV/RTV 300/50 mg, 200/50
      mg, and 200/100 mg once daily. METHODS: A total of 288 ATV and 312 RTV plasma
      concentrations from 30 patients were included to build a population PK model
      using the stochastic approximation expectation maximization algorithm implemented
      in MONOLIX 3.2 software. RESULTS: A one-compartment model with first-order
      absorption and lag-time best described the data for both drugs in the final
      simultaneous model. A maximum-effect model in which RTV inhibited the elimination
      of ATV was used to describe the relationship between RTV concentrations and ATV
      clearance (CL/F). An RTV concentration of 0.22 mg/L was associated with 50%
      maximum inhibition of ATV CL/F. The population prediction of ATV CL/F in the
      absence of RTV was 16.6 L/h (relative standard error, 7.0%), and the apparent
      volume of distribution and absorption rate constant were 106 L (relative standard
      error, 8%) and 0.87 per hour (fixed), respectively. Simulated average ATV trough
      concentrations at ATV/RTV 300/50 mg, 200/50 mg, and 200/100 mg once daily were
      45%, 63%, and 33% lower, respectively, than that of the standard dose.
      CONCLUSION: Although simulated median ATV trough concentrations after dose
      reductions were still more than the ATV minimum effective concentration (2.9-,
      1.9-, and 3.6-fold for ATV/RTV 300/50 mg, 200/50 mg, and 200/100 mg,
      respectively); our modeling predicted a high proportion of individuals with
      subtherapeutic trough concentrations on the 200/50 mg dose. This suggests that
      300/50 mg and 200/100 mg dosing are preferred candidate regimens in future
      clinical studies.

PMID- 23011397
TI  - Measuring retention in HIV care: the elusive gold standard.
AB  - BACKGROUND: Measuring retention in HIV primary care is complex, as care includes
      multiple visits scheduled at varying intervals over time. We evaluated 6 commonly
      used retention measures in predicting viral load (VL) suppression and the
      correlation among measures. METHODS: Clinic-wide patient-level data from 6
      academic HIV clinics were used for 12 months preceding implementation of the
      Centers for Disease Control and Prevention/Health Resources and Services
      Administration (CDC/HRSA) retention in care intervention. Six retention measures
      were calculated for each patient based on scheduled primary HIV provider visits:
      count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit
      constancy, and the HRSA HIV/AIDS Bureau (HRSA HAB) retention measure. Spearman
      correlation coefficients and separate unadjusted logistic regression models
      compared retention measures with one another and with 12-month VL suppression,
      respectively. The discriminatory capacity of each measure was assessed with the c
      statistic. RESULTS: Among 10,053 patients, 8235 (82%) had 12-month VL measures,
      with 6304 (77%) achieving suppression (VL <400 copies/mL). All 6 retention
      measures were significantly associated (P < 0.0001) with VL suppression (odds
      ratio; 95% CI, c-statistic): missed visit count (0.73; 0.71 to 0.75, 0.67),
      missed visit dichotomous (3.2; 2.8 to 3.6, 0.62), visit adherence (3.9; 3.5 to
      4.3,0.69), gap (3.0; 2.6 to 3.3, 0.61), visit constancy (2.8; 2.5 to 3.0, 0.63),
      and HRSA HAB (3.8; 3.3 to 4.4, 0.59). Measures incorporating "no-show" visits
      were highly correlated (Spearman coefficient = 0.83-0.85), as were measures based
      solely on kept visits (Spearman coefficient = 0.72-0.77). Correlation
      coefficients were lower across these 2 groups of measures (range = 0.16-0.57).
      CONCLUSIONS: Six retention measures displayed a wide range of correlation with
      one another, yet each measure had significant association and modest
      discrimination for VL suppression. These data suggest there is no clear gold
      standard and that selection of a retention measure may be tailored to context.

PMID- 23011399
TI  - Medicinal and recreational marijuana use among HIV-infected women in the Women's
      Interagency HIV Study (WIHS) cohort, 1994-2010.
AB  - BACKGROUND: Despite the major benefits of effective antiretroviral therapy on HIV
      related survival, there is an ongoing need to help alleviate medication side
      effects related to antiretroviral therapy use. Initial studies suggest that
      marijuana use may reduce HIV-related symptoms, but medical marijuana use among
      HIV-infected individuals has not been well described. METHODS: The authors
      evaluated trends in marijuana use and reported motivations for use among 2776 HIV
      infected women in the Women's Interagency HIV Study between October 1994 and
      March 2010. Predictors of any and daily marijuana use were explored in
      multivariate logistic regression models clustered by person using generalized
      estimating equation. In 2009, participants were asked if their marijuana use was
      medical, "meaning prescribed by a doctor," or recreational, or both. RESULTS:
      Over the 16 years of this study, the prevalence of current marijuana use
      decreased significantly from 21% to 14%. In contrast, daily marijuana use almost
      doubled from 3.3% to 6.1% of all women and from 18% to 51% of current marijuana
      users. Relaxation, appetite improvement, reduction of HIV-related symptoms, and
      social use were reported as common reasons for marijuana use. In 2009, most
      marijuana users reported either purely medicinal use (26%) or both medicinal and
      recreational usage (29%). Daily marijuana use was associated with higher CD4 cell
      count, quality of life, and older age. Demographic characteristics and risk
      behaviors were associated with current marijuana use overall but were not
      predictors of daily use. CONCLUSIONS: This study suggests that both recreational
      and medicinal marijuana use are relatively common among HIV-infected women in the
      United States.

PMID- 23011400
TI  - Patient retention from HIV diagnosis through one year on antiretroviral therapy
      at a primary health care clinic in Johannesburg, South Africa.
AB  - OBJECTIVE: To compare patient retention at 3 stages of pre-antiretroviral (ART)
      care and 2 stages of post-ART care to identify when greatest attrition occurs.
      DESIGN: An observational cohort study. METHODS: We reviewed files of all adult
      nonpregnant individuals testing HIV-positive January 1-June 30, 2010, at a
      primary health clinic in Johannesburg, South Africa (N = 842). We classified
      retention in pre-ART stage 1 (HIV diagnosis to CD4 results notification in <=3
      months), pre-ART stage 2 (initially ineligible for ART with repeat CD4 test <=1
      year of prior CD4), pre-ART stage 3 (initiating ART <=3 months after first
      eligible CD4 result), and at 0-6 and 6-12 months post-ART. RESULTS: Retention
      among all patients during pre-ART stage 1 was 69.8% [95% confidence interval
      (CI): 66.7% to 72.9%]. For patients initially ART ineligible (n = 221), 57.4%
      (95% CI: 49.5% to 65.0%) returned for a repeat CD4 during pre-ART stage 2. Among
      those who were ART eligible (n = 589), 73.5% (95% CI: 69.0% to 77.6%) were
      retained during pre-ART stage 3. Retention increased with time on ART, from 80.2%
      (95% CI: 75.3% to 84.5%) at 6 months to 95.3% (95% CI: 91.7% to 97.6%) between 6
      and 12 months. Cumulative retention from diagnosis to 12 months on ART was 36.9%
      (95% CI: 33.0% to 41.1%) for those ART eligible and 43.0% (95% CI: 36.4% to
      49.8%) from diagnosis to repeat CD4 testing within one year among those ART
      ineligible. CONCLUSIONS: Patient attrition in the first year after HIV diagnosis
      was greatest before ART initiation: more than 25% at each of 3 pre-ART stages. As
      countries expand HIV testing and ART programs, success will depend on linkage to
      care, especially before ART eligibility and initiation.

PMID- 23011402
TI  - Coincidence of biophoton emission by wheat seedlings during simultaneous,
      transcontinental germination tests.
AB  - Measurements of spontaneous ultra-weak light (biophoton) emission from native
      Brazilian and German wheat seedlings in three simultaneous series of germination
      tests are presented, two run in Germany and one in Brazil. Seedlings in both
      countries presented semi-circadian rhythms of emission that were in accordance
      with the local lunisolar gravimetric tidal acceleration, as did seeds which had
      been transported from Brazil to Germany. The simultaneity of the photon emission
      patterns in all tests argues for the lunisolar tide and its rhythmic variations
      as regulators of the natural rhythm of photon emission. However, seedlings from
      seed samples transported from Brazil to Germany showed, in addition, a temporary
      disturbance within the emission periodicity which may indicate a possible short
      term acclimatization to the new location.

PMID- 23011401
TI  - Roles of the different components of magnesium chelatase in abscisic acid signal
      transduction.
AB  - The H subunit of Mg-chelatase (CHLH) was shown to regulate abscisic acid (ABA)
      signaling and the I subunit (CHLI) was also reported to modulate ABA signaling in
      guard cells. However, it remains essentially unknown whether and how the Mg
      chelatase-catalyzed Mg-protoporphyrin IX-production differs from ABA signaling.
      Using a newly-developed surface plasmon resonance system, we showed that ABA
      binds to CHLH, but not to the other Mg-chelatase components/subunits CHLI, CHLD
      (D subunit) and GUN4. A new rtl1 mutant allele of the CHLH gene in Arabidopsis
      thaliana showed ABA-insensitive phenotypes in both stomatal movement and seed
      germination. Upregulation of CHLI1 resulted in ABA hypersensitivity in seed
      germination, while downregulation of CHLI conferred ABA insensitivity in stomatal
      response in Arabidopsis. We showed that CHLH and CHLI, but not CHLD, regulate
      stomatal sensitivity to ABA in tobacco (Nicotiana benthamiana). The
      overexpression lines of the CHLD gene showed wild-type ABA sensitivity in
      Arabidopsis. Both the GUN4-RNA interference and overexpression lines of
      Arabidopsis showed wild-type phenotypes in the major ABA responses. These
      findings provide clear evidence that the Mg-chelatase-catalyzed Mg-ProtoIX
      production is distinct from ABA signaling, giving information to understand the
      mechanism by which the two cellular processes differs at the molecular level.

PMID- 23011403
TI  - Nucleolar chromatin organization at different activities of soybean root
      meristematic cell nucleoli.
AB  - Nucleolar chromatin, including nucleolus-associated chromatin as well as active
      and inactive condensed ribosomal DNA (rDNA) chromatin, derives mostly from
      secondary constrictions known as nucleolus organizer regions containing rDNA
      genes on nucleolus-forming chromosomes. This chromatin may occupy different
      nucleolar positions being in various condensation states which may imply
      different rDNA transcriptional competence. Sections of nucleoli originating from
      root meristematic cells of soybean seedlings grown at 25  degrees C (the
      control), then subjected to chilling stress (10  degrees C), and next transferred
      again to 25  degrees C (the recovery) were used to measure profile areas occupied
      by nucleolar condensed chromatin disclosed with sodium hydroxide methylation
      acetylation plus uranyl acetate technique. The biggest total area of condensed
      chromatin was found in the nucleoli of chilled plants, while the smallest was
      found in those of recovered plants in relation to the amounts of chromatin in the
      control nucleoli. The condensed nucleolar chromatin, in the form of different
      sized and different-shaped clumps, was mainly located in fibrillar centers. One
      can suppose that changes of condensed rDNA chromatin amounts might be a mechanism
      controlling the number of transcriptionally active rDNA genes as the nucleoli of
      plants grown under these experimental conditions show different transcriptional
      activity and morphology.

PMID- 23011404
TI  - In vitro inhibitory effects of imatinib mesylate on stromal cells and
      hematopoietic progenitors from bone marrow.
AB  - Imatinib mesylate (IM) is used to treat chronic myeloid leukemia (CML) because it
      selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis.
      Recent studies have shown that IM inhibits the growth of several non-malignant
      hematopoietic and fibroblast cells from bone marrow (BM). The aim of the present
      study was to evaluate the effects of IM on stromal and hematopoietic progenitor
      cells, specifically in the colony-forming units of granulocyte/macrophage (CFU
      GM), using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The
      results showed that low concentrations of IM (1.25 uM) reduced the growth of CFU
      GM in clonogenic assays. In culture assays with stromal cells, fibroblast
      proliferation and alpha-SMA expression by immunocytochemistry analysis were also
      reduced in a concentration-dependent manner, with a survival rate of
      approximately 50% with a dose of 2.5 uM. Cell viability and morphology were
      analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells
      were found to be viable after treatment with 5 uM IM, although there was gradual
      growth inhibition of fibroblastic cells while the number of round cells
      (macrophage-like cells) increased. At higher concentrations (15 uM), the majority
      of cells were apoptotic and cell growth ceased completely. Oil red staining
      revealed the presence of adipocytes only in untreated cells (control). Cell cycle
      analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases
      in groups treated with 5-15 uM. These results suggest that IM differentially
      inhibits the survival of different types of BM cells since toxic effects were
      achieved.

PMID- 23011405
TI  - IL-6 upregulation contributes to the reduction of miR-26a expression in
      hepatocellular carcinoma cells.
AB  - A recent study showed that miR-26a is downregulated in hepatocellular carcinoma
      tissues and that this downregulation is an independent predictor of survival.
      Interestingly, the same study also reported that miR-26a downregulation causes a
      concomitant elevation of IL-6 expression. Because miR-26a expression was found to
      be transcriptionally downregulated by oncogene c-Myc in various cancers, and the
      expression of c-Myc was increased by IL-6 stimulation, we hypothesized that IL-6
      contributes to reduction of miR-26a in hepatocellular carcinoma. Serum IL-6 was
      measured by ELISA and miR-26a was detected by qRT-PCR. The data of 30 patients
      with hepatocellular carcinoma who had undergone surgical tumor resection revealed
      that serum IL-6 could be considered to be a predictor of survival up to 5 years
      for hepatocellular carcinoma patients (log-rank test, P < 0.05). We observed that
      the serum IL-6 concentration was inversely correlated with miR-26a expression in
      cancerous tissues (Pearson correlation test, r = -0.651, P < 0.01). Furthermore,
      by in vitro experiments with HepG2 cells, we showed that IL-6 stimulation can
      lead to miR-26a suppression via c-Myc activation, whereas in normal hepatocyte
      LO2 cells incubation with IL-6 had no significant effect on miR-26a expression.
      Taken together, these results indicate that miR-26a reduction in hepatocellular
      carcinoma might be due to IL-6 upregulation.

PMID- 23011406
TI  - High sensitivity C-reactive protein distribution in the elderly: the Bambui
      Cohort Study, Brazil.
AB  - The measurement of the serum concentration of the acute-phase reactant C-reactive
      protein (CRP) provides a useful marker in clinical practice. However, the
      distribution of CRP is not available for all age and population groups. This
      study assessed the distribution of high sensitivity-CRP (hs-CRP) by gender and
      age in 1470 elderly individuals from a Brazilian community that participates in
      the Bambui Cohort Study. Blood samples were collected after 12 h of fasting and
      serum samples were stored at -70 degrees C. Measurements were made with a
      commercial hs-CRP immunonephelometric instrument. More than 50% of the results
      were above 3.0 mg/L for both genders. Mean hs-CRP was higher in women (3.62 +/-
      2.58 mg/L) than in men (3.03 +/- 2.50 mg/L). This difference was observed for all
      ages, except for the over-80 age group. This is the first population-based study
      to describe hs-CRP values in Latin American elderly subjects. Our results
      indicate that significant gender differences exist in the distribution of hs-CRP,
      and suggest that gender-specific cut-off points for hs-CRP would be necessary for
      the prediction of cardiovascular risks.

PMID- 23011407
TI  - Psychiatric disorders and cardiac anxiety in exercising and sedentary coronary
      artery disease patients: a case-control study.
AB  - Regular physical exercise has been shown to favorably influence mood and anxiety;
      however, there are few studies regarding psychiatric aspects of physically active
      patients with coronary artery disease (CAD). The objective of the present study
      was to compare the prevalence of psychiatric disorders and cardiac anxiety in
      sedentary and exercising CAD patients. A total sample of 119 CAD patients (74
      men) were enrolled in a case-control study. The subjects were interviewed to
      identify psychiatric disorders and responded to the Cardiac Anxiety
      Questionnaire. In the exercise group (N = 60), there was a lower prevalence (45
      vs 81%; P < 0.001) of at least one psychiatric diagnosis, as well as multiple
      comorbidities, when compared to the sedentary group (N = 59). Considering the
      Cardiac Anxiety Questionnaire, sedentary patients presented higher scores
      compared to exercisers (mean +/- SEM = 55.8 +/- 1.9 vs 37.3 +/- 1.6; P < 0.001).
      In a regression model, to be attending a medically supervised exercise program
      presented a relevant potential for a 35% reduction in cardiac anxiety. CAD
      patients regularly attending an exercise program presented less current
      psychiatric diagnoses and multiple mental-related comorbidities and lower scores
      of cardiac anxiety. These salutary mental effects add to the already known health
      benefits of exercise for CAD patients.

PMID- 23011408
TI  - Neuronal networks in west syndrome as revealed by source analysis and
      renormalized partial directed coherence.
AB  - West syndrome is a severe epileptic encephalopathy of infancy with a poor
      developmental outcome. This syndrome is associated with the pathognomonic EEG
      feature of hypsarrhythmia. The aim of the study was to describe neuronal networks
      underlying hypsarrhythmia using the source analysis method (dynamic imaging of
      coherent sources or DICS) which represents an inverse solution algorithm in the
      frequency domain. In order to investigate the interaction within the detected
      network, a renormalized partial directed coherence (RPDC) method was also applied
      as a measure of the directionality of information flow between the source
      signals. Both DICS and RPDC were performed for EEG delta activity (1-4 Hz) in
      eight patients with West syndrome and in eight patients with partial epilepsies
      (control group). The brain area with the strongest power in the given frequency
      range was defined as the reference region. The coherence between this reference
      region and the entire brain was computed using DICS. After that, the RPDC was
      applied to the source signals estimated by DICS. The results of electrical source
      imaging were compared to results of a previous EEG-fMRI study which had been
      carried out using the same cohort of patients. As revealed by DICS, delta
      activity in hypsarrhythmia was associated with coherent sources in the occipital
      cortex (main source) as well as the parietal cortex, putamen, caudate nucleus and
      brainstem. In patients with partial epilepsies, delta activity could be
      attributed to sources in the occipital, parietal and sensory-motor cortex. In
      West syndrome, RPDC showed the strongest and most significant direction of
      ascending information flow from the brainstem towards the putamen and cerebral
      cortex. The neuronal network underlying hypsarrhythmia in this study resembles
      the network which was described in previous EEG-fMRI and PET studies with
      involvement of the brainstem, putamen and cortical regions in the generation of
      hypsarrhythmia. The RPDC suggests that brainstem could have a key role in the
      pathogenesis of West syndrome. This study supports the theory that hypsarrhythmia
      results from ascending brainstem pathways that project widely to basal ganglia
      and cerebral cortex.

PMID- 23011409
TI  - The effects of topical coenzyme Q10 and vitamin E D-alpha-tocopheryl polyethylene
      glycol 1000 succinate after cataract surgery: a clinical and in vivo confocal
      study.
AB  - PURPOSE: To evaluate the postoperative effects of topical coenzyme Q(10) +
      vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate (CoQ(10)) after
      cataract surgery. METHODS: 40 consecutive patients were randomized to receive
      CoQ(10) or saline solution (SS) twice daily for 9 months after uneventful
      cataract surgery with a temporal port. Before surgery, on day 14 and at months 3,
      6 and 9, they underwent non-invasive break-up time (NIBUT) testing, Schirmer
      test, BUT, aesthesiometry as well as in vivo confocal microscopy of the subbasal
      nerve plexus of the cornea (SBP). The density of the subbasal nerves was
      calculated in the central (CFD) and temporal (TFD) cornea (number of fibres per
      field). RESULTS: On day 14, surgery reduced CFD and TFD, respectively, by 25-35
      and 50%; indices of ocular surface stability were all impaired. The treatment
      with CoQ(10) was associated with faster nerve regeneration than SS (at month 3,
      CFD +1.5 +/- 1.9 vs. +0.2 +/- 1.8, p = 0.04, and TFD +2.5 +/- 1.7 vs. +1.0 +/-
      1.6, p = 0.007; at month 6, TFD +2.7 +/- 1.9 vs. +1.4 +/- 1.5, p = 0.02) and
      better stability of ocular surface (NIBUT and BUT) throughout the study. No
      relevant side effects were found, apart from occasional burning in 10% of CoQ(10)
      patients. CONCLUSIONS: Changes of the corneal nerves occurring after cataract
      surgery may influence the integrity of the ocular surface. Treatment with topical
      CoQ(10) has a positive effect in restoring SBP anatomy and ocular surface
      stability.

PMID- 23011411
TI  - Deficiencies in numerical models of anisotropic nonlinearly elastic materials.
AB  - Incompressible nonlinearly hyperelastic materials are rarely simulated in finite
      element numerical experiments as being perfectly incompressible because of the
      numerical difficulties associated with globally satisfying this constraint. Most
      commercial finite element packages therefore assume that the material is slightly
      compressible. It is then further assumed that the corresponding strain-energy
      function can be decomposed additively into volumetric and deviatoric parts. We
      show that this decomposition is not physically realistic, especially for
      anisotropic materials, which are of particular interest for simulating the
      mechanical response of biological soft tissue. The most striking illustration of
      the shortcoming is that with this decomposition, an anisotropic cube under
      hydrostatic tension deforms into another cube instead of a hexahedron with non
      parallel faces. Furthermore, commercial numerical codes require the specification
      of a 'compressibility parameter' (or 'penalty factor'), which arises naturally
      from the flawed additive decomposition of the strain-energy function. This
      parameter is often linked to a 'bulk modulus', although this notion makes no
      sense for anisotropic solids; we show that it is essentially an arbitrary
      parameter and that infinitesimal changes to it result in significant changes in
      the predicted stress response. This is illustrated with numerical simulations for
      biaxial tension experiments of arteries, where the magnitude of the stress
      response is found to change by several orders of magnitude when infinitesimal
      changes in 'Poisson's ratio' close to the perfect incompressibility limit of 1/2
      are made. 

PMID- 23011412
TI  - Noninvasive therapy for the management of patients with advanced coronary artery
      disease.
AB  - OBJECTIVES: To determine the efficacy of cardiac shock wave therapy (CSWT) in the
      management of patients with end-stage coronary artery disease (CAD).
      INTRODUCTION: Patients with end-stage CAD have symptoms such as recurrent angina,
      breathlessness, and other debilitating conditions. End-stage CAD patients are
      usually those who have angina pectoris following a coronary artery bypass surgery
      or a percutaneous coronary intervention. These patients are refractory to optimal
      medical therapy and not fit for a redo procedure, and are often termed as 'no
      option' patients. METHODS: We carried out a prospective cohort study to examine
      the effects of CSWT application in patients who had end-stage CAD and were no
      option patients. Characteristics such as angina class scores and functional
      status scores among cases (patients with end-stage CAD who received CSWT) and
      controls (patients with end-stage CAD who did not receive CSWT) were compared at
      baseline and at 6 months after CSWT therapy. RESULTS: There were 43 patients in
      the case group and 43 patients in the control group. The mean age of the patients
      was 58.7 +/- 9.5 years in the case group and 56.6 +/- 11.6 years in the control
      group. Other characteristics such as the prevalence of diabetes, hypertension,
      coronary artery bypass graft and percutaneous coronary intervention were similar
      in both groups. Clinical results showed a significant improvement in exercise
      time between the cases and the controls 6 months after treatment with CSWT (20.1
      +/- 15.7 min in cases vs. 10.1 +/- 4.2 min in controls; P<0.0001), and
      symptomatic improvement in the CCS class scores (1.95 +/- 0.80 in cases and 2.63
      +/- 0.69 in controls; P<0.0001) and NYHA class scores (1.95 +/- 0.80 in cases vs.
      2.48 +/- 0.59 in controls; P<0.001). In the control group, there was no
      improvement in angina class, functional class and exercise time. CONCLUSION: The
      present study shows that CSWT application to the ischemic myocardium in patients
      with refractory angina pectoris improved symptoms and reduced the severity of
      ischemic areas at 6 months after CSWT treatment compared with the baseline. No
      side effects were observed with this therapy.

PMID- 23011413
TI  - Impact of clopidogrel resistance on ST-segment resolution and no-reflow in acute
      myocardial infarction with ST-elevation patients treated with a primary
      percutaneous coronary intervention.
AB  - INTRODUCTION: A rapid restoration of epicardial coronary flow in acute myocardial
      infarction is crucial for saving jeopardized myocardium. The no-reflow phenomenon
      is one of the major problems in a primary percutaneous coronary intervention
      (PCI) and may be defined as an outcome of different pathological pathways. Our
      aim was to evaluate clopidogrel resistance in patients who underwent primary PCI
      and the relationship with the no-reflow phenomenon. MATERIALS AND METHODS: A
      total of 127 patients (mean age 54.0 +/- 11.4 years, 83.7% men) were assessed for
      this purpose. No-reflow was defined as less than 50% ST-segment resolution on
      ECG. RESULT: No-reflow was significantly frequent in patients with clopidogrel
      resistance (25.3 vs. 57.1%, P=0.006). Univariate analysis and multivariate
      analysis showed that clopidogrel resistance and anterior myocardial infarction
      were only independent predictors of no-reflow phenomenon in patients treated with
      a primary PCI during acute myocardial infarction. CONCLUSION: Our study showed
      that clopidogrel resistance may be one of the responsible mechanisms for the no
      reflow phenomenon. Assessment of simple ECG after a primary PCI may help
      clinicians to determine patients with a poor prognosis.

PMID- 23011414
TI  - High SYNTAX score predicts worse in-hospital clinical outcomes in patients
      undergoing primary angioplasty for acute myocardial infarction.
AB  - OBJECTIVE: A high SYNTAX score (SXscore) is a predictor of adverse outcomes for
      stable and unstable coronary syndromes. We aimed to examine whether a high
      SXscore will determine in-hospital clinical outcomes in patients with ST
      elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention. METHODS: A total of 646 (mean age 56.1 +/- 12.5; 516 males, 130
      females) patients with STEMI undergoing a primary percutaneous coronary
      intervention were evaluated prospectively. The study population was divided into
      tertiles based on the SXscore values. A high SXscore (n=196) was defined as a
      value in the third tertile (>21.75), and a low SXscore (n=450) was defined as a
      value in the lower two tertiles (<=21.75). Patients were followed up for in
      hospital clinical outcomes. RESULTS: In-hospital cardiovascular mortality
      occurred more in the high SXscore group than in the low SXscore group (10.7 and
      2.4%, respectively, P<0.001). In a receiver-operating characteristic curve
      analysis, an SXscore value of 21.75 was identified as an effective cut point in
      STEMI for in-hospital cardiovascular mortality (area under curve=0.75, 95%
      confidence interval: 0.66-0.83, P<0.001). An SXscore value of more than 21.75
      yielded a sensitivity of 66% and a specificity of 71.5%. A significant
      association was noted between a high SXscore level and the adjusted risk of in
      hospital cardiovascular mortality (odds ratio: 3.92, 95% confidence interval: 1.1
      13.9, P=0.03). CONCLUSION: Our findings showed that patients with a high SXscore
      undergoing primary angioplasty for STEMI have a poor in-hospital survival, and
      that a high SXscore represents an independent risk factor for in-hospital
      cardiovascular mortality.

PMID- 23011415
TI  - [The early diagnostic of somatic inflammatory diseases in patients with acute
      ischemic stroke].
AB  - We examined 29 patients with acute ischemic stroke. Measurement of plasma nitrite
      and N-nitroso-compounds (NO2- +RNNO) to test for the presence of acute
      inflammatory process allows to timely and definitely determine its onset before
      the development of clinical symptoms and to operatively control the treatment,
      the latter being particularly important due to the restricted communication
      ability of neurologic patients.

PMID- 23011410
TI  - Cell signaling, post-translational protein modifications and NMR spectroscopy.
AB  - Post-translationally modified proteins make up the majority of the proteome and
      establish, to a large part, the impressive level of functional diversity in
      higher, multi-cellular organisms. Most eukaryotic post-translational protein
      modifications (PTMs) denote reversible, covalent additions of small chemical
      entities such as phosphate-, acyl-, alkyl- and glycosyl-groups onto selected
      subsets of modifiable amino acids. In turn, these modifications induce highly
      specific changes in the chemical environments of individual protein residues,
      which are readily detected by high-resolution NMR spectroscopy. In the following,
      we provide a concise compendium of NMR characteristics of the main types of
      eukaryotic PTMs: serine, threonine, tyrosine and histidine phosphorylation,
      lysine acetylation, lysine and arginine methylation, and serine, threonine O
      glycosylation. We further delineate the previously uncharacterized NMR properties
      of lysine propionylation, butyrylation, succinylation, malonylation and
      crotonylation, which, altogether, define an initial reference frame for
      comprehensive PTM studies by high-resolution NMR spectroscopy.

PMID- 23011418
TI  - [The cluster analysis of depression symptoms in elderly patients].
AB  - The vast number of clinical and psychopathological studies of depression in
      elderly patients is based on the simple description of symptoms. In the present
      paper, authors studied clinical and psychopathological symptoms of depression in
      elderly people using statistical cluster analysis. Four main clusters of
      psychopathological symptoms were singled out. The further cluster analysis
      revealed significant between-group differences in clinical and anamnesis
      information that were not included in the analysis. Based on this finding, we
      proposed that each cluster reflected a specific clinical type of depression in
      the old age. The atypical combination within each type did not allow to identify
      definitely the nosological attribution of depression according to current
      classifications. In conclusion, the study of the psychopathology of depression in
      elderly people using methods of multivariate statistics makes it possible to find
      new clinical variants of these disorders that may improve diagnosis and allow for
      differentiation of treatment.

PMID- 23011421
TI  - [The follow-up study of childhood-onset schizophrenia: clinical and social
      aspects].
AB  - Fifty-eight patients, 13 girls and 45 boys, with early-onset schizophrenia (mean
      5.4 years) were followed up for 9.5 years. The men age at end point was 19.7
      years. Full remission or recovery was not identified in any of the patients. The
      partial remission was observed in 14 (24%) patients and 44 (76%) patients had
      chronic course without remissions. Two thirds of patients were disabled including
      9 patients with severe, 25 patients with moderate and 1 patient with mild
      disability. Most of the patients (62%) became disabled in childhood. Fourteen
      patients need the constant care and control from caregivers; 24 patients were
      able to work in special conditions, 20 patients can live independently and
      support themselves; 57 patients lived with parents and 1 patient was married. It
      has been concluded that notwithstanding the intensive psychopharmacotherapy and
      rehabilitative programs, patients with early-onset schizophrenia show poor
      outcomes. Therefore, new social-therapeutic approaches for providing care to
      these patients are needed.

PMID- 23011423
TI  - [Efficacy of reflexology in the combination with neuroprotective treatment in
      hemiparetic form of children cerebral palsy].
AB  - Sixty patients with the diagnosis of cerebral palsy with hemiparesis at the age
      from 2 to 7 years were treated. All 60 patients had conventional treatment
      including massage and exercise therapy. Patients were divided into 2 randomized
      groups. The patients of the first group were given 3 sets of microcurrent
      reflexology sessions and 2 courses of treatment with cortexin. Patients of the
      second group were given reflexology treatments only. The microcurrent reflexology
      treatment included 15 sessions using the apparatus MAKS. Cortexin was introduced
      intramuscularly in dosage 10 mg. The bottle content was diluted in 2 ml of 0.5%
      novocaine. The treatment included 10 injections. This treatment showed the
      beneficial effects: 29 patients of the first group (97%) and 27 patients of the
      second group (90%) developed some ambulation skills. The progress in complicated
      manipulative activity of paralyzed upper extremities under microcurrent
      reflexology with cortexin was 2.2 times more visible in patients of the first
      group compared to the second one (11 patients (37%) versus 5 patients (17%),
      respectively). Positive changes in the encephalon functional status according to
      electroencephalography results were found in 21 patients (71%) of the first group
      and in 16 patients (53%) of the second group.

PMID- 23011425
TI  - [The use of the QMGS for quantitative assessment of the severity of movement
      disorders in patients with myasthenia].
AB  - The MRC scale is traditionally used for assessment of the severity of movement
      disorders. The patients' effort is graded on a scale of 0-5. The use of this
      scale is limited by subjective biases and inadequate assessment of some
      functions. The quantitative scale for assessment of the severity of clinical
      symptoms of myasthenia (QMGS) allows to evaluate pathological muscle
      fatigability, the main syndrome of this disease, which is important for
      evaluating the severity of symptoms before and after the pathogenetic treatment
      or when probes with the introduction of acetylcholinesterase preparations are
      used.

PMID- 23011427
TI  - [The neurodegenerative process in multiple sclerosis and the possible
      neuroprotective effect of treatment with Beta-interferon 1a (avonex)].
AB  - The aim of the study was to investigate the change of NAA/Cr ratio in the brain
      parenchyma in patients with MS with the help of protonic multivoxel magnetic
      resonance spectroscopy (PMMRS) and to detect the correlation between this factor
      and clinical status of the patients. The study was also performed in order to
      investigate whether this method can be potentially used for monitoring of the
      severity of the disease and severity of the neurodegenerative process. On the
      basis of this knowledge potential neuroprotective effect of the interferon beta
      1a (IFN Beta1a) i.m. (avonex) was investigated. Twenty six patients with
      relapsing-remitting multiple sclerosis (RRMS) were included in the study. The
      procedures included examination of the history of the disease, neurological
      examination, EDSS, neuropsychological tests, dynamic MRI with PMMRS. The decrease
      of the NAA/Cr ratio in patients with RRMS compared to healthy controls was
      detected. The dynamic control in a year revealed the decrease NAA/Cr in patients
      with MS. Negative association was revealed between NAA/Cr in the brain and the
      level of neurological and cognitive deficit. The analysis of the 1 year therapy
      with IFN Beta1a i.m. revealed neuroprotective effect which can be related to the
      possible positive effect of the drug on the neurodegenaration process.

PMID- 23011429
TI  - [Clinical-genetic characteristics of hereditary motor-sensory neuropathy type 1
      X].
AB  - Data of own researches and the review of the literary data for studying
      pathogenesis and features of HMSN, type 1 X caused by mutations in gene GJB1 are
      presented in this paper. X-linked HMSN is the genetic variant second for
      frequency in Russian, it constitute 22% from total of patients of this group.
      Features of this genetic variant are considerable distinction in weight clinical
      displays at patients man's and female. It is shown that at the majority of female
      patients clinical displays are expressed less, and at 20% were absent at all. The
      assumption is come out that at indicators of CNV from 35 to 52 m/s, it is
      necessary to conduct research in gene GJB1 especially at patients of a female and
      as to carry out search of mutations at all relatives with HMSN, type 1 X even in
      the absence of complaints from their party.

PMID- 23011431
TI  - [Effect of Catechol-O-methyltransferase deficiency on reinforcing effects of
      cocaine (experimental study)].
AB  - Catechol-O-methyltransferase (COMT) remains an important regulatory element in
      prefrontal cortex dopamine homeostasis. The literature data suggest that
      individual differences in COMT activity (Val158Met polymorphism) might have
      indirect downstream effects on the reward system. The aim of the present study
      was to examine whether COMT deletion affects reinforcing effects of cocaine in
      mice. The study was conducted in male mice with homozygous COMT deletion as well
      as their C57BL/6J wild-type littermates. Animals were trained to nose-poke to
      receive response-contingent intravenous infusions of cocaine (0.3 mg/kg per
      infusion; final schedule of reinforcement - fixed ratio (FR) 3 time out 30 s).
      Following the initial acquisition phase, cocaine self-administration dose-effect
      functions (0.03, 0.1, 0.3, 1, and 3 mg/kg per infusion) were determined under FR3
      and progressive ratio (PR) schedules of reinforcement. Cocaine dose-dependently
      maintained responding under FR3 and PR schedule of reinforcement when the unit
      dose of cocaine was varied across the sessions. The total cocaine intake did not
      differ in COMT deletion mice and wild-type mice. The results of this study
      suggest that individual differences in COMT activity do not affect primary
      reinforcing effects of cocaine in mice.

PMID- 23011433
TI  - [History of the neurology school of Nizhny Novgorod].

PMID- 23011434
TI  - [The effect of ozone therapy on the level of blood cholesterol in cerebrovascular
      pathology].

PMID- 23011435
TI  - [Transcranial magnetic stimulation in chronic tension-type headache].
AB  - In the treatment of 30 patients with chronic tension-type headache have included
      transcranial magnetic stimulation apparatus "TAMAS". The course of treatment was
      5 procedures. We evaluated the severity of pain on a visual analogue scale (VAS),
      the portability procedures, the possible local and general side effects. We
      compared performance before and after therapy. Showed a reduction in headache
      intensity on a scale of VAS, improved general well-being.

PMID- 23011437
TI  - [Lipid metabolism in Parkinson's disease].

PMID- 23011438
TI  - [The use of cytoflavin in the complex treatment of patients with tick-borne
      encephalitis].

PMID- 23011439
TI  - [Ectopic thymoma in a female patient with late-onset myasthenia].

PMID- 23011440
TI  - [Electroencephalogram characteristics in the assessment of cognitive functions].

PMID- 23011441
TI  - [Structural and functional brain changes in emotional disorders: foundation of
      neurocirculatory and neurotrophic hypothesis of depression].

PMID- 23011444
TI  - Inorganic photoisomerization: the case study of rhenium(I) complexes.
AB  - The mechanism of photoisomerization of stilbene-like ligands coordinated to
      rhenium polypyridine or alpha-diimine carbonyls is deciphered in the light of
      recent theoretical results obtained at various levels of theory, density
      functional theory (DFT, time-dependent DFT) and state-of-the-art ab initio
      methods, complete active space self-consistent field (CASSCF) and multi-state CAS
      perturbation theory 2nd Order (MS-CASPT2). On the basis of the electronic
      absorption spectra and potential energy profiles (PEF) associated to the low
      lying singlet and triplet intra-ligand (IL) and metal-to-ligand-charge-transfer
      (MLCT) excited states, coupled by spin-orbit interactions and calculated for the
      series [Re(CO)(3)(N,N)(L)](+) with N,N = bpy, phen and ph(2)phen (bpy = 2,2'
      bipyridine; phen = 1,10-phenanthroline; ph(2)phen = 4,7-diphenyl-1,10
      phenanthroline) and L = stpy or bpe (stpy = 4-styrylpyridine; bpe = 1,2-bis(4
      pyridylethylene) it is shown that the dynamics of the isomerization process are
      controlled by several features: (i) the occurrence of a (1)IL(L)/(1)MLCT(NN)
      conical intersection in the vicinity of the (1)MLCT(NN) absorption domain (ii)
      the kinetics of (1)MLCT(NN)/(3)MLCT(NN) intersystem crossings; (iii) the kinetics
      of (3)MLCT(NN)/(3)IL(L) internal conversion. The branching ratio between the two
      main isomerization pathways, namely along the (1)IL(L) PEF
      via(1)MLCT(NN)/(1)IL(L) internal conversion at the conical intersection or along
      the (3)IL(L) PEF after (3)MLCT(NN)/(3)IL(L) charge transfer is largely influenced
      by the nature of the N,N antenna and L isomerizable ligands.

PMID- 23011446
TI  - Postnatal catch-up fat after late preterm birth.
AB  - BACKGROUND: Late preterm birth accounts for 70% of preterm births. The aim of the
      study was to investigate the postnatal weight gain and weight gain composition
      changes in a cohort of late preterm infants. METHODS: A total of 49 late preterm
      infants (mean birth weight 2,496 +/- 330 g and gestational age 35.2 +/- 0.7 wks)
      underwent growth and body composition assessment by an air displacement
      plethysmography system on the fifth day of life, at term, and at 1 and 3 mo of
      corrected age. The reference group was composed of 40 healthy, full-term, breast
      fed infants. RESULTS: The late preterm infants showed a Delta fat mass gain
      between birth and term-corrected age equal to 182%. As compared with full-term
      infants, at term and 1 mo of corrected age mean weight (3,396 +/- 390 vs. 3,074
      +/- 409 g and 4,521 +/- 398 vs. 4,235 +/- 673 g, respectively) and percentage of
      fat mass (16.1 +/- 4.6 vs. 8.9 +/- 2.9 and 22.6 +/- 4.2 vs. 17.4 +/- 4.0,
      respectively) were significantly higher in late preterm infants, whereas no
      difference among groups was found at 3 mo. CONCLUSION: Rapid postnatal catch-up
      fat was found in these infants. Further studies are needed to investigate whether
      this short-term increase in fat mass may modulate the risk of chronic diseases or
      represent an adaptive mechanism to extrauterine life.

PMID- 23011445
TI  - Social inequalities in mental health: results from the EU contribution to the
      World Mental Health Surveys Initiative.
AB  - PURPOSE: The objective of the present study was to provide updated data from nine
      European countries about the impact of social inequalities in the prevalence of
      common mental disorders. METHODS: Cross-sectional household survey of a
      representative sample of the adult general population of Belgium, Bulgaria,
      Germany, Italy, The Netherlands, Northern Ireland, Portugal, Romania and Spain.
      In total, 34,395 individuals were included. Social inequalities in 12-month mood,
      anxiety and alcohol-related disorders were evaluated. RESULTS: In Europe, income
      seems not to be related to the prevalence of mental disorders. Unemployment and
      disablement are associated with mental disorders. Lower educational level
      augments the risk for mood disorders. Living in small (rural) areas decreases the
      risk for mood disorders and living in urban settings increases it. Northern
      Ireland, Portugal and Belgium are the countries with the highest risks for mental
      disorders. CONCLUSIONS: Despite some contradictions with previous literature, in
      Europe there are social inequalities in the prevalence of mental disorders.
      However, income showed not to be associated with inequalities in mental health.
      Being younger, unemployed or disabled, with no education or incomplete primary
      studies, living in urban settings, and in Northern Ireland, Portugal or Belgium
      were associated to an augmented prevalence of mental disorders. Policy makers
      could focus on mental health promotion and mental disorders prevention programmes
      for risk groups such as unemployed/disabled individuals. Support to vulnerable
      groups (unemployed or those with less education) and mental health literacy can
      improve European citizens' mental health.

PMID- 23011447
TI  - Preoperative embolisation of choroid plexus tumours in children: part I-does the
      reduction of perioperative blood loss affect the safety of subsequent surgery?
AB  - OBJECTIVE: Operative management of choroid plexus tumours is hindered by
      excessive bleeding and significant CSF production. Our aim was to assess whether
      the use of preoperative embolisation would increase the safety of surgery by
      reducing the perioperative blood loss and achieve higher rates of resection of
      the tumour. METHODS: Between 1996 and 2009, 30 patients (mean age 2.25 years)
      with choroid plexus tumours (24 papillomas, 6 carcinomas) were treated. Fifteen
      of them underwent preoperative super-selective embolisation of the feeding
      vessels with histoacryl glue. The perioperative blood loss as a percentage of
      estimated blood volume loss (EBV) was recorded together with mortality and
      morbidity of the two groups (embolised, EMB+ vs. not, EMB-). RESULTS: The
      embolisation was successful in 13/15 (86.6 %) patients. This manoeuvre rendered
      the tumour relatively avascular making the operative field "less hazardous" as
      reported by the surgeon. In addition, higher gross total resection rate was
      achieved (100 vs. 41 %; p = 0.001) at the first operative attempt in the EMB+
      group. The percentage EBV loss was 96 % in EMB- group vs. 224 % in EMB+ group (p
      = 0.038). CONCLUSION: Our observations with regards to preoperative embolisation
      of choroid plexus tumours show an acceptable safety profile for the endovascular
      technique. At the same time, it renders the operative treatment of the tumours
      safer by reducing perioperative blood loss resulting in a high gross total
      resection rate. In summary, we suggest that preoperative embolisation is a useful
      adjunct that should be considered prior to surgical resection in managing these
      patients.

PMID- 23011448
TI  - Craniospinal dissemination of filum myxopapillary ependymoma following spinal
      trauma: case report and literature review.
AB  - BACKGROUND: Myxopapillary ependymoma is a rare benign variant of ependymoma,
      occurring most commonly in the cauda equina/filum terminale of the spinal cord.
      It is rare in pediatric patients. Dissemination of the myxopapillary ependymoma
      along the neuraxis is uncommon both in adults and pediatric patients. METHODS: We
      report a 16-year-old boy with dissemination of the myxopapillary ependymoma along
      the neuraxis following spinal trauma. The possible mechanisms of tumor
      dissemination are discussed with a review of the literature.

PMID- 23011449
TI  - Few characteristics of dengue's fever epidemiology in Brazil.

PMID- 23011450
TI  - Global dengue epidemiology trends.

PMID- 23011451
TI  - Clinical experience in dengue: experience of specialized service.

PMID- 23011452
TI  - Laboratory diagnosis for dengue.

PMID- 23011453
TI  - Challenges in the control of Aedes aegypti.

PMID- 23011454
TI  - Development of Sanofi Pasteur tetravalent dengue vaccine.

PMID- 23011455
TI  - Designing a vaccination strategy against dengue.
AB  - In this work we propose a mathematical approach to estimate the dengue force of
      infection, the average age of dengue first infection, the optimum age to
      vaccinate children against dengue in a routine fashion and the optimum age
      interval to introduce the dengue vaccine in a mass vaccination campaign. The
      model is based on previously published models for vaccination against other
      childhood infections, which resulted in actual vaccination programmes in Brazil.
      The model was applied for three areas of distinct levels of endemicity of the
      city of Recife in Northeastern State of Pernambuco, Brazil. Our results point to
      an optimal age to introduce the dengue vaccine in the routine immunization
      programme at two years of age and an age interval to introduce a mass vaccination
      between three and 14 years of age.

PMID- 23011456
TI  - National immunization program: vaccination, compliance and pharmacovigilance.

PMID- 23011457
TI  - Q&A session 06 October 2011: I International Symposium on Dengue, FMUSP, Sao
      Paulo.

PMID- 23011458
TI  - Journal of Sao Paulo Institute of Tropical Medicine. Editorial.

PMID- 23011459
TI  - Veteran-specific suicide prevention.
AB  - Suicide rates have been increasing in some subgroups of Veteran populations, such
      as those who have experienced combat. Several initiatives are addressing this
      critical need and the Department of Veterans Affairs (VA) has been recognized for
      its leadership. This integrative review adopts the Research Impact Framework
      (RIM) to address suicide-specific prevention activities targeting Veterans. The
      RIM is a standardized approach for developing issue narratives using four broad
      areas: societal-related impacts, research-related impacts, policy-related
      impacts, and service-related impacts. The questions addressed in this review are:
      (1) What are the major initiatives in Veteran-specific suicide prevention in four
      areas of impact-society, research, policy, and services? (2) Are there gaps
      related in each impact area? and (3) What are the implications of this narrative
      for other strategies to address suicide prevention targeting Veterans? Systematic
      application of the RIM identifies exemplars, milestones, gaps, and health
      disparity issues.

PMID- 23011460
TI  - Improving the diagnostic accuracy of hiatal hernia in patients undergoing
      bariatric surgery.
AB  - BACKGROUND: Surgical correction of hiatal hernia (HH) during bariatric surgery
      has been found to improve patient outcomes and decrease reoperation rate.
      Although barium esophagram is more sensitive than endoscopy for detection of HH,
      accurate preoperative diagnosis remains a challenge. The aim of this study is to
      determine whether diagnostic accuracy improves by utilizing right anterior
      oblique (RAO) esophagram technique instead of the commonly used upright technique
      when comparing to the gold standard of intraoperative detection. METHODS: All
      patients undergoing bariatric surgery were prospectively evaluated for HH by
      barium esophagram. After the first 69 patients, the technique was changed from
      upright to RAO. Hiatal hernia was assessed intraoperatively by laxity of the
      phrenoesophageal ligament and, if present, was repaired posteriorly. Two board
      certified radiologists specializing in gastrointestinal radiology, who were
      blinded to the intraoperative results, retrospectively reviewed the esophagrams.
      Consensus reads were utilized for divergent opinions. Sensitivity and specificity
      were calculated for each technique. RESULTS: Between 2008 and 2010, a total of
      388 patients underwent preoperative esophagrams (69 upright, 388 RAO). For
      upright esophagram, sensitivity was 50 % and specificity was 97 %. For RAO
      esophagram, sensitivity was 70 % and specificity was 77 %. RAO had a lower
      percentage of false negatives (11 vs. 21 %) than upright esophagram. CONCLUSIONS:
      The use of RAO technique for preoperative esophagram is more sensitive for
      diagnosis of hiatal hernia than upright esophagram. If surgeons desire routine
      preoperative esophagram, RAO technique is the best.

PMID- 23011461
TI  - Five-year changes in psychiatric treatment status and weight-related
      comorbidities following bariatric surgery in a veteran population.
AB  - BACKGROUND: Although bariatric surgery is an established treatment for obesity,
      less is known regarding the long-term effects of surgery on psychiatric function.
      This paper reports changes in psychiatric treatment status, weight, and weight
      related comorbidities over 5 years of follow-up among a population of veterans
      completing bariatric surgery. METHODS: We assessed 55 veterans undergoing
      bariatric surgery at a single Veteran Affairs medical center for 5 years post
      surgery. Patients completed a pre-surgery clinical interview with a licensed
      psychologist. Using computerized medical records, we tracked pre- to post-surgery
      involvement with antidepressants, anxiolytics, psychotherapies, and overall
      psychiatric treatment visits along with changes in weight and metabolic function.
      RESULTS: Rates of antidepressant use and/or involvement with psychotherapy for
      depression declined from 56.4 % at pre-surgery to 34.6 % at 5 years post-surgery,
      p = 0.01. Anxiolytic use and/or involvement with psychotherapy for anxiety,
      however, increased from 23.6 to 32.7 % pre- to 5 years post-surgery. Average
      psychiatric treatment volume remained similar to pre-surgery status across follow
      up. These mixed indicators of psychiatric improvement occurred despite marked
      metabolic improvements from surgery. Mean percent excess weight loss = 51.7 and
      41.3 (1 and 5 years post-surgery, respectively), systolic blood pressure (-6.8
      mmHg (14.3)/-6.1 mmHg (12.8), respectively), glucose levels (-18.6 mg/dL (30.2)/
      10.0 mg/dL (25.9), respectively), triglycerides (-78.2 mg/dL (96.7)/-69.1 mg/dL
      (102.2), respectively) and high-density lipoproteins (+7.1 (9.9)/+11.3 (11.3),
      respectively) levels each improved. CONCLUSIONS: We report evidence of decreased
      antidepressant use and depression therapies following bariatric surgery, but no
      improvements on rates of anxiolytic use and anxiety therapies or on overall
      psychiatric treatment involvement. Despite metabolic improvements, bariatric
      patients with psychiatric histories may warrant ongoing attention to mental
      health.

PMID- 23011462
TI  - Laparoscopic Roux-en-Y vs. mini-gastric bypass for the treatment of morbid
      obesity: a 10-year experience.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the gold
      standard for the treatment of morbid obesity but is technically challenging and
      results in significant perioperative complications. While laparoscopic mini
      gastric bypass (LMGB) has been reported to be a simple and effective treatment
      for morbid obesity, controversy exists. Long-term follow-up data from a large
      number of patients comparing LMGB to LRYGB are lacking. METHODS: Between October
      2001 and September 2010, 1,657 patients who received gastric bypass surgery
      (1,163 for LMGB and 494 for LRYGB) for their morbid obesity were recruited from
      our comprehensive obesity surgery center. Patients who received revision
      surgeries were excluded. Minimum follow-up was 1 year (mean 5.6 years, from 1 to
      10 years). The operative time, estimated blood loss, length of hospital stay, and
      operative complications were assessed. Late complication, changes in body weight
      loss, BMI, quality of life, and comorbidities were determined at follow-up.
      Changes in quality of life were assessed using the Gastrointestinal Quality of
      Life Index. RESULTS: There was no difference in preoperative clinical parameters
      between the two groups. Surgical time was significantly longer for LRYGB (159.2
      vs. 115.3 min for LMGB, p < 0.001). The major complication rate was borderline
      higher for LRYGB (3.2 vs. 1.8%, p = 0.07). At 5 years after surgery, the mean BMI
      was lower in LMGB than LRYGB (27.7 vs. 29.2, p < 0.05) and LMGB also had a higher
      excess weight loss than LRYGB (72.9 vs. 60.1%, p < 0.05). Postoperative
      gastrointestinal quality of life increased significantly after operation in both
      groups without any significant difference at 5 years. Obesity-related clinical
      parameters improved in both groups without significant difference, but LMGB had a
      lower hemoglobin level than LRYGB. Late revision rate was similar between LRYGB
      and LMGB (3.6 vs. 2.8%, p = 0.385). CONCLUSIONS: This study demonstrates that
      LMGBP can be regarded as a simpler and safer alternative to LRYGB with similar
      efficacy at a 10-year experience.

PMID- 23011463
TI  - Predictors for remission of major components of the metabolic syndrome after
      biliopancreatic diversion with duodenal switch (BPDDS).
AB  - BACKGROUND: Metabolic surgery causes the remission of type 2 diabetes mellitus
      (T2DM), hypertension, and hyperlipidemia to varying degrees, depending on the
      patient characteristics and the surgical procedure. The aim of this study was to
      find predictors for the remission of T2DM and hypertension after biliopancreatic
      diversion with duodenal switch (BPDDS). METHODS: Eighty patients with T2DM were
      followed up for 2 years or more after BPDDS, and changes in body weight and
      metabolic status were noted. Remission was defined as fasting glucose <7 mmol/l
      with HbA1C <6.5 %, blood pressure <140/90 mmHg, and low-density lipoprotein (LDL)
      <2.6 mmol without the use of medication. RESULTS: Preoperatively, the mean age
      was 44 years, body mass index (BMI) was 48 kg/m(2), and duration of diabetes was
      5 years. Of the 80 patients, 38 patients were using insulin, 48 patients were
      using antihypertensives, and 38 patients were using a lipid-lowering drug. Five
      percent of the patients had recommended levels for HbA1C, blood pressure, and LDL
      prior to the operation. The remission rate at 2 years was 94 % for T2DM, 54 % for
      hypertension, and 86 % for LDL hyperlipidemia. Preoperative predictors for
      nonremission of T2DM were a higher BMI, insulin usage, and low insulin C-peptide,
      and for hypertension, older age and more severe hypertension. Postoperative
      weight loss was important for both. CONCLUSIONS: Surgical intervention with BPDDS
      is an effective treatment of T2DM, hypertension, and hyperlipidemia. The duration
      of T2DM and age of the patient are the most important preoperative predictors for
      the remission of T2DM and hypertension, respectively.

PMID- 23011464
TI  - "Our sickness record is a national disgrace": Adelle Davis, nutritional
      determinism, and the anxious 1970s.
AB  - America's most widely read nutritionist of the postwar decades, Adelle Davis,
      helped to shape Americans' eating habits, their child-feeding practices, their
      views about the quality of their food supply, and their beliefs about the impact
      of nutrition on their emotional and physical health. This paper closely examines
      Davis's writings and argues that even though she is often associated with
      countercultural food reformers like Alice Waters and Frances Moore Lappe, she had
      as much in common with the writings of interwar nutritionists and home
      economists. While she was alarmed about the impact of pesticides and food
      additives on the quality of the food supply, and concerned about the declining
      fertility of American soil, she commanded American women to feed their families
      better and promised that improved nutrition would produce stronger, healthier,
      more beautiful children who would ensure America's future strength. She believed
      that nearly every health problem could be solved through nutrition, and urged her
      readers to manage their diets carefully and to take extensive supplementation to
      ensure optimum health. As such, she played an important role in creating the
      ideology of "nutritionism" - the idea that food should be valued more for its
      constituent parts than for its pleasures or cultural significance. 

PMID- 23011465
TI  - Intermolecular G-quadruplex-based universal quencher free molecular beacon.
AB  - A simple and universal quencher-free molecular beacon (MB) with low background
      fluorescence is developed based on an intermolecular G-quadruplex signaling
      probe. Unlike previous fluorescent MB strategies, it can function without any
      fluorophore and quencher modifications on its hairpin sequence.

PMID- 23011466
TI  - Assessment of safety and efficacy of methylsulfonylmethane on bone and knee
      joints in osteoarthritis animal model.
AB  - Methylsulfonylmethane (MSM), which is one of the popular ingredients of so-called
      health foods in Japan, is expected to relieve inflammation in arthritis and
      allergies. However, there is no scientific evidence to confirm the efficacy and
      safety of MSM in detail. In this study, we examined the effects of MSM on
      cartilage formation in growing rats (G) and cartilage degradation in STR/Ort mice
      (A), an accepted human osteoarthritis (OA) model. For cartilage formation study,
      6-week-old growing male Wister rats were assigned to four groups to receive a
      control or MSM-containing diet. To examine the efficacy of MSM on the cartilage
      of OA model mouse, 10-week-old male STR/OrtCrlj mice were assigned to three
      groups to receive a control or MSM-containing diet. The dosages used were amounts
      equal to the recommended supplements for humans [0.06 g/kg body weight (BW)/day:
      MSM1G and MSM1A], 10 fold higher (0.6 g/kg BW/day: MSM10G and MSM10A), and 100
      fold higher (6 g/kg BW/day: MSM100G). Intake of MSM for 4 weeks did not affect
      cartilage formation in the knee joint in growing rats. Body, liver, and spleen
      weight in the MSM100G group were significantly lower than those in the control
      group. Intake of MSM for 13 weeks decreased degeneration of the cartilage at the
      joint surface in the knee joints in STR/Ort mice in a dose-dependent manner.
      These results suggest that appropriate intake of MSM is possibly effective in OA
      model mice; however, intake of large amounts of MSM induced atrophy of several
      organs.

PMID- 23011468
TI  - Epoxyeicosatrienoic acid pathway in human health and diseases.
AB  - In response to endothelial cell activation, arachidonic acid can be converted by
      cytochrome P450 (CYP) epoxygenases to epoxyeicosatrienoic acids (EETs), which
      have potent vasodilator and anti-inflammatory properties. EETs are rapidly
      degraded in vivo to the less active dihydroxyeicosatrienoic acids (DHETs) by
      soluble epoxide hydrolase (sEH). Since the beginning of the 2000s, the role of
      EET pathway in human health and its alteration in diseases has been shown by
      measuring EETs/DHET levels in blood, by evaluating the relationship between
      CYP/sEH gene polymorphisms, which modify enzyme activity and thus EETs/DHET
      level, and by assessing the inhibitory effect of the local administration of CYP
      epoxygenase inhibitor on endothelium-dependent dilatation. By combining these
      functional and biological approaches, we demonstrated that EETs are the
      endothelial factors released by CYP epoxygenases involved in the flow-mediated
      dilatation of conduit arteries in healthy subjects, together with the impairment
      of EET availability in essential hypertensive patients at this level. The
      modulation of EET pathway now emerges as a new promising pharmacological target
      that may improve the clinical management of patients at high cardiovascular risk.
      In this respect, the restoration of EET availability using a new class of agents,
      the inhibitors of sEH, gave promising results in various animal models of
      cardiovascular diseases, reducing blood pressure and target organ damage, and a
      first product has entered clinical evaluation.

PMID- 23011467
TI  - Clinically applicable antianginal agents suppress osteoblastic transformation of
      myogenic cells and heterotopic ossifications in mice.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder
      characterized by progressive heterotopic ossification. FOP is caused by a gain-of
      function mutation in ACVR1 encoding the bone morphogenetic protein type II
      receptor, ACVR1/ALK2. The mutant receptor causes upregulation of a
      transcriptional factor, Id1. No therapy is available to prevent the progressive
      heterotopic ossification in FOP. In an effort to search for clinically applicable
      drugs for FOP, we screened 1,040 FDA-approved drugs for suppression of the Id1
      promoter activated by the mutant ACVR1/ALK2 in C2C12 cells. We found that that
      two antianginal agents, fendiline hydrochloride and perhexiline maleate,
      suppressed the Id1 promoter in a dose-dependent manner. The drugs also suppressed
      the expression of native Id1 mRNA and alkaline phosphatase in a dose-dependent
      manner. Perhexiline but not fendiline downregulated phosphorylation of Smad 1/5/8
      driven by bone morphogenetic protein (BMP)-2. We implanted crude BMPs in muscles
      of ddY mice and fed them fendiline or perhexiline for 30 days. Mice taking
      perhexiline showed a 38.0 % reduction in the volume of heterotopic ossification
      compared to controls, whereas mice taking fendiline showed a slight reduction of
      heterotopic ossification. Fendiline, perhexiline, and their possible derivatives
      are potentially applicable to clinical practice to prevent devastating
      heterotopic ossification in FOP.

PMID- 23011469
TI  - Developmental programming of eNOS uncoupling and enhanced vascular oxidative
      stress in adult rats after transient neonatal oxygen exposure.
AB  - The authors have previously shown that neonatal hyperoxic stress leads to high
      blood pressure, impaired endothelium-mediated vasodilatation, and increased
      vascular production of superoxide anion by NAD(P)H oxidase in adulthood. However,
      it is unknown whether changes in nitric oxide (NO) production and/or
      bioinactivation prevail and whether NO synthase (NOS) is also a source of
      superoxide. The purpose of this study was to evaluate whether adult animals
      exposed to neonatal hyperoxic stress have impaired vascular NO production
      associated with NOS uncoupling participating to vascular superoxide production
      and vascular dysfunction. In adult male rats exposed to 80% oxygen from day 3 to
      10 of life (H, n = 6) versus room air controls (CTRL, n = 6), vascular (aorta) NO
      production is decreased at baseline (CTRL: 21 +/- 1 vs. H: 16 +/- 2 4,5
      diaminofluorescein diacetate fluorescence intensity arbitrary units; P < 0.05)
      and after carbachol stimulation (acetylcholine analog; CTRL: 26 +/- 2 vs. H: 18+/
      2; P < 0.05). Pretreatment with L-arginine (CTRL: 32 +/- 4 vs. H: 31 +/- 5) and L
      sepiapterine [analog of key NOS cofactor tetrahydro-L-biopterin (BH4)] (CTRL: 30
      +/- 3 vs. H: 29 +/- 3) normalizes NO production after carbachol. L-Sepiapterine
      also normalizes impaired vasodilatation to carbachol. Vascular endothelial NO
      synthase (eNOS) immunostaining is reduced, whereas total eNOS protein expression
      is increased in H (CTRL: 0.76 +/- 0.08 vs. H: 1.76+/- 0.21; P < 0.01). The
      significantly higher superoxide generation (CTRL: 20 +/- 2 vs. H: 28 +/- 3
      hydroethidine fluorescence intensity arbitrary units; P < 0.05) is prevented by
      pretreatment with the eNOS inhibitor N-nitro-L-arginine methyl ester (CTRL: 21 +/
      4 vs. H: 22 +/- 4). Taken together, the current data indicate a role for eNOS
      uncoupling in enhanced vascular superoxide, impaired endothelium-mediated
      vasodilatation, and decreased NO production in adult animals with programmed
      elevated blood pressure after a brief neonatal oxygen exposure.

PMID- 23011470
TI  - Reduction of aldosterone production improves renal oxidative stress and fibrosis
      in diabetic rats.
AB  - Aldosterone is increased in diabetes and contributes to the development of
      diabetic nephropathy. The authors hypothesized that reduction in aldosterone
      production in diabetes by amlodipine or aliskiren improves diabetic kidney
      disease by attenuating renal oxidative stress and fibrosis. Normoglycemic and
      streptozotocin-induced diabetic Sprague-Dawley rats were given vehicle,
      amlodipine, or aliskiren alone and combined for 6 weeks. At the end of study, we
      evaluated blood pressure (BP), 24-hour urinary sodium (UNaV) and aldosterone
      excretion rates, renal interstitial fluid (RIF) levels of nitric oxide (NO),
      cyclic guanosine 3',5'-monophosphate (cGMP), and 8-isoprostane, and renal
      morphology. BP was not significantly different between any of experimental
      groups. UNaV increased in diabetic animals and was not affected by different
      treatments. Urinary aldosterone excretion increased in diabetic rats receiving
      vehicle and decreased with amlodipine and aliskiren alone or combined. RIF NO and
      cGMP levels were reduced in vehicle-treated diabetic rats and increased with
      amlodipine or aliskiren given alone and combined. RIF 8-isoprostane levels and
      renal immunostaining for periodic acid-Schiff and fibronectin were increased in
      vehicle-treated diabetic rats and decreased with aliskiren alone or combined with
      amlodipine. The authors conclude that inhibition of aldosterone by amlodipine or
      aliskiren ameliorates diabetes induced renal injury via improvement of NO-cGMP
      pathway and reduction in oxidative stress and fibrosis, independent of BP
      changes.

PMID- 23011472
TI  - Luminescent gels by self-assembling platinum complexes.
AB  - A platinum complex bearing a tetraethylene glycol chain has been designed and its
      self-assembly properties investigated. In solution, only a yellow phosphorescence
      of the aggregated species is observed. The complex gives luminescent gels of
      different colours with DCM and DMF, reaching up to 60% photoluminescence quantum
      yield.

PMID- 23011471
TI  - Rho-associated coiled-coil-containing kinase 2 deficiency in bone marrow-derived
      cells leads to increased cholesterol efflux and decreased atherosclerosis.
AB  - BACKGROUND: Macrophages play a central role in the development of
      atherosclerosis. However, the signaling pathways that regulate their function are
      not well understood. The Rho-associated coiled-coil-containing kinases (ROCK1 and
      ROCK2) are serine-threonine protein kinases that are involved in the regulation
      of the actin cytoskeleton. Recent studies suggest that ROCK1 in macrophages and
      bone marrow-derived cells mediates atherogenesis. However, a similar role for
      ROCK2 in the pathogenesis of atherosclerosis has not been determined. METHODS AND
      RESULTS: The bone marrows from wild-type, ROCK2(+/-), and ROCK2(-/-) mice were
      transplanted into irradiated recipient low-density lipoprotein receptor(-/-)
      mice, and atherosclerosis was induced with a 16-week high-cholesterol diet.
      Compared with wild-type bone marrow-transplanted mice, ROCK2(+/-) bone marrow
      transplanted and ROCK2(-/-) bone marrow-transplanted mice showed substantially
      less lipid accumulation in the aorta (8.46+/-1.42% and 9.80+/-2.34% versus
      15.64+/-1.89%; P<0.01 for both) and decreased atherosclerotic lesions in the
      subaortic sinus (158.1+/-44.4 and 330.1+/-109.5*10(3)MUm(2) versus 520.2+/
      125.7*10(3)MUm(2); P<0.01 for both). These findings correlated with decreased
      foam cell formation (2.27+/-0.57 versus 4.10+/-0.3; P<0.01) and increased
      cholesterol efflux (17.65+/-0.6 versus 9.75+/-0.8; P<0.05) in ROCK2-deficient
      mice that are mediated, in part, through the peroxisome proliferator-activated
      receptor-gamma/liver X receptor/ATP-binding cassette transporter A1 pathway in
      macrophages. CONCLUSIONS: ROCK2 contributes to atherosclerosis, in part, by
      inhibiting peroxisome proliferator-activated receptor-gamma-mediated reverse
      cholesterol transport in macrophages, which contributes to foam cell formation.
      These findings suggest that inhibition of ROCK2 in macrophages may have
      therapeutic benefits in preventing the development of atherosclerosis.

PMID- 23011473
TI  - Influence of eugenol on the push-out bond strengths of fiber posts cemented with
      different types of resin luting agents.
AB  - This study evaluated the influence of eugenol on the push-out bond strengths of
      fiber posts cemented with different types of resin luting agents. Seventy-two
      extracted maxillary single-rooted canine teeth were randomly divided into two
      groups of 36 teeth. Group 1, the control group, was filled with gutta-percha only
      (i.e., did not receive eugenol), whereas group 2 was filled with a eugenol
      containing sealer. All root canals were filled and each group was divided into
      three subgroups. The posts in each subgroup were cemented with the following
      materials: subgroup 1 with a 2-step self-etching adhesive system (Clearfil Liner
      Bond 2V + Panavia F); subgroup 2 with a 1-step self-etching adhesive (Panavia F);
      and subgroup 3 with a self-adhesive (Clearfil SA Cement). Dislodgement resistance
      was measured using a universal testing machine. All data were subjected to ANOVA
      using a factorial design and Tukey test (alpha = 0.05). The use of the eugenol
      containing sealer significantly reduced the push-out bond strength of the fiber
      post (P < 0.05). The push-out bond strength of Panavia F was significantly higher
      than those of the other groups filled with the eugenol-containing sealer (P <
      0.05). The Panavia F group was less susceptible to the inhibiting effect of
      eugenol than were the other evaluated groups when the fiber post was cemented in
      the canals filled with the eugenol-containing sealer. 

PMID- 23011474
TI  - The effect of temperature and contact time of sodium hypochlorite on human roots
      infected with Enterococcus faecalis and Candida albicans.
AB  - The aim of this study was to evaluate the effectiveness of 2.5 % NaOCl at
      different temperature and time intervals on Enterococcus faecalis and Candida
      albicans-infected human roots. A total of 112 root cylinders prepared from
      extracted single-rooted humans were infected by E. faecalis (Group A, n = 56) or
      C. albicans (Group B, n = 56); 3 root cylinders served as negative controls. Both
      groups were further divided into 6 subgroups according to three contact times (30
      s, 1 min, 5 min) with NaOCl at two different temperatures (25 or 37  degrees C).
      Microorganism growth was controlled at the 24th and 48th hours. Statistical
      analysis was performed using the Chi-square test. While NaOCl at 25  degrees C
      for 5 min was the most effective irrigation regimen to eliminate E. faecalis (p <
      0.001), NaOCl at 37  degrees C for 5 min exhibited significantly superior
      antifungal properties (p < 0.05). At the same contact times, difference in the
      temperature of NaOCl did not affect the growth of either E. faecalis or C.
      albicans. As a result, the irrigation time of NaOCl was more effective than the
      temperature to eliminate E. faecalis, while pre-heating of NaOCl to 37  degrees C
      increased its effectiveness on C. albicans at 5 min contact time.

PMID- 23011475
TI  - The influence of electrospun fibre scaffold orientation and nano-hydroxyapatite
      content on the development of tooth bud stem cells in vitro.
AB  - In stem cell-based dental tissue engineering, the goal is to create tooth-like
      structures using scaffold materials to guide the dental stem cells. In this
      study, the effect of fiber alignment and hydroxyapatite content in biodegradable
      electrospun PLGA scaffolds have been investigated. Fiber orientation of the
      scaffolds was random or aligned in bundles. For scaffolds with prefabricated
      orientation, scaffolds were fabricated from PLGA polymer solution containing 0,
      10 or 20 % nano-hydroxyapatite. The scaffolds were seeded with porcine cells
      isolated from tooth buds (dental mesenchymal, dental epithelial, and mixed dental
      mesenchymal/epithelial cells). Samples were collected at 1, 3 and 6 weeks.
      Analyses were performed for cell proliferation, ALP activity, and cell
      morphology. Fiber alignment showed an effect on cell orientation in the first
      week after cell seeding, but had no long-term effect on cell alignment or
      organized calcified matrix deposition once the cells reach confluency. Scaffold
      porosity was sufficient to allow migration of mesenchymal cells. Hydroxyapatite
      incorporation did not have a positive effect on cell proliferation, especially of
      epithelial cells, but seemed to promote differentiation. Concluding, scaffold
      architecture is important to mesenchymal cell morphology, but has no long-term
      effect on cell alignment or organized ECM deposition. nHA incorporation does have
      an effect on cell proliferation, differentiation and ECM production, and should
      be regarded as a bioactive component of dental bioengineered scaffolds.

PMID- 23011476
TI  - Chiral imidate-ferrocenylphosphanes: synthesis and application as P,N-ligands in
      iridium(I)-catalyzed hydrogenation of unfunctionalized and poorly functionalized
      olefins.
AB  - A small library of chiral imidate-ferrocenylphosphane ligands was efficiently
      synthesized (8 examples) and evaluated in the iridium(I)-catalyzed hydrogenation
      of unfunctionalized and poorly functionalized olefins. These catalysts perform
      very well in a range of examples (yields and ee's up to 100%).

PMID- 23011477
TI  - Elbow MR imaging findings in patients with synovial fringe syndrome.
AB  - OBJECTIVE: To describe imaging findings in patients with synovial fringe (SF)
      syndrome of the elbow and to compare with a control population. MATERIALS AND
      METHODS: Nine patients (5 men, 4 women) whose mean age was 35.7 years were
      diagnosed with SF syndrome and had undergone preoperative elbow MRI. The
      radiohumeral (RH) plica was assessed for thickness, cross-sectional area,
      coverage of one third or more of the radial head, blunting of the free edge, and
      T2 signal intensity abnormality. Other abnormalities of the RH joint were also
      assessed, including adjacent articular cartilage defects, subcortical bone marrow
      signal abnormality in the capitellum, and synovitis. Results were compared with
      15 control patients who were asymptomatic laterally and posteriorly. RESULTS:
      Mean thickness and cross-sectional area of the RH plica were 1.8 mm and 19.4
      mm(2) respectively in controls, compared with 2.5 mm and 21.9 mm(2) respectively
      in symptomatic patients. No statistically significant differences in the
      distribution of the mean thickness or cross-sectional area of the RH plica were
      found between the two groups. However, 67% of SF syndrome patients had a RH plica
      thickness greater than 2.6 mm compared with only 13% of controls (p = 0.021).
      Other abnormalities of the RH plica occurred more frequently in patients with SF
      syndrome compared with controls, but were not statistically significant.
      CONCLUSION: In patients presenting with posterolateral pain or mechanical
      symptoms in the elbow, RH plica thickness greater than 2.6 mm on elbow MRI
      examinations may help identify patients with SF syndrome.

PMID- 23011478
TI  - Importance of anthropogenic metals in hospital and urban wastewater: its
      significance for the environment.
AB  - Thirty-four metals were analyzed by ICP-MS. Among these elements, anthropogenic
      silver, gadolinium and platinum, were representative markers of medical
      activities in hospital and urban wastewater. On working days, median hospital
      wastewater concentrations for anthropogenic silver, gadolinium, and platinum were
      approximately three, 13 and 27 times higher respectively than the Municipal
      wastewater. A drastic reduction of their emission was observed during non-working
      days (minus 94 % for gadolinium and 87 % for platinum). A large percentage of
      these metals are not trapped in the Treatment Plant, i.e. 88 % for gadolinium and
      69 % for platinum. More than 4 kg and 350 g for gadolinium and platinum are
      respectively discharged per year in the River Seine. Therefore, it is imperative
      to eliminate these elements in the Plant.

PMID- 23011479
TI  - Health related quality of life and emotional health in children with chronic
      granulomatous disease: a comparison of those managed conservatively with those
      that have undergone haematopoietic stem cell transplant.
AB  - PURPOSE: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency
      that predisposes to life-threatening infections and inflammation. Haematopoietic
      stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of
      life. Children with haematological malignancies report improved quality of life
      post-HSCT. There are no data for children with CGD. This study evaluated quality
      of life and emotional well-being in CGD children treated conventionally or
      transplanted. METHODS: Parents and children completed the Pediatric Quality of
      Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ).
      Mean scores were compared with published UK norms. Comparisons were made for
      those that had or had not undergone HSCT. RESULTS: Forty-seven parents completed
      PedsQL (children aged 3-15). Twenty-one were post-HSCT. Forty-two completed SDQ
      (children aged 3-15). Nineteen post-HSCT. Median age for non-HSCT group 9 years.
      Median age for post-HSCT group 10 years. The HSCT group were median 3 years post
      HSCT (range 1-9 years). HSCT survival was 90 %-two died without completing
      questionnaires Parent and self-reported quality of life for non-transplanted
      children was significantly lower than healthy children. Parents reported
      increased emotional difficulties compared to published norms. PedsQL and SDQ
      scores for transplanted children were not significantly different from healthy
      norms. CONCLUSIONS: This study demonstrates the quality of life is reduced in
      CGD. Transplanted patients have quality of life comparable to levels reported in
      healthy children. This data will help inform families and clinicians when
      deciding about treatment and may have relevance for other immunodeficiencies
      treated with transplant.

PMID- 23011480
TI  - Processed meat consumption and risk of cancer: a multisite case-control study in
      Uruguay.
AB  - BACKGROUND: The role of processed meat in the aetiology of several cancers was
      explored in detail. METHODS: In the time period 1996-2004, a multisite case
      control study was conducted in Montevideo, Uruguay. The study included 6 060
      participants (3 528 cases and 2 532 controls) corresponding to cancers of the
      oral cavity, pharynx, oesophagus, stomach, colon, rectum, larynx, lung, female
      breast, prostate, urinary bladder, and kidney (renal cell carcinoma only).
      RESULTS: The highest odds ratios (ORs) were positively associated with cancers of
      the colon, rectum, stomach, oesophagus, and lung. With the exception of renal
      cell carcinoma, the remaining cancer sites were significantly associated with
      elevated risks for processed meat consumption. Furthermore, mortadella, salami,
      hot dog, ham, and salted meat were strongly associated with risk of several
      cancer sites. CONCLUSION: It could be concluded that processed meat intake could
      be a powerful multiorgan carcinogen.

PMID- 23011481
TI  - Breast cancer and ductal carcinoma in situ among women with prior squamous or
      glandular precancer in the cervix: a register-based study.
AB  - BACKGROUND: Human papillomavirus and hormonal contraceptives may be risk factors
      for cervical precancer and malignant breast tumours. METHODS: Standardised
      incidence ratios (SIRs) of malignant breast tumours during 1970-2008 were
      estimated separately for women with prior squamous and glandular cervical
      precancer. RESULTS: Women with squamous precancer and women with glandular
      precancer in the cervix had a significantly higher risk of malignant breast
      tumours than the general female population (SIR, 95% confidence interval: 1.10,
      1.05-1.14 and 1.52, 1.11-2.08, respectively). INTERPRETATION: Shared risk factors
      or screening attendance may explain the excess risk of malignant breast tumours
      among women with a history of cervical precancer.

PMID- 23011482
TI  - Comment on 'a comparison of three methods for detecting KRAS mutations in
      formalin-fixed colorectal cancer specimens'.

PMID- 23011483
TI  - Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer
      survival: a cohort study.
AB  - BACKGROUND: Aspirin has been widely reported to reduce the incidence of
      colorectal cancer. Recently, a survival benefit after diagnosis has also been
      suggested. Data regarding such a benefit are to date contradictory. This study
      examines the effect of non-steroidal anti-inflammatory drug (NSAID) use on
      mortality in colorectal cancer in a larger patient cohort than previously to
      further clarify this effect, especially in terms of exposure timing and dosing.
      METHODS: A study using the General Practice Research Database assessed whether
      aspirin or NSAID exposure in the year immediately following diagnosis affected
      all-cause mortality in a cohort of 13 994 colorectal cancer patients. Cox
      proportional hazards modelling adjusted for age, gender, smoking, body mass index
      and comorbidity. RESULTS: Overall mortality was slightly lower in patients
      treated with aspirin, (hazard ratio (HR)=0.91; 95% confidence interval (CI)=0.82
      1.00). This effect was observed only in patients treated with prophylaxis-dose
      aspirin (HR=0.89, CI=0.80-0.98) and only in patients taking aspirin before
      diagnosis (HR=0.86, CI=0.76-0.98). Differential effects were observed depending
      on the time after diagnosis. Up to 5 years, a reduction in mortality was observed
      for aspirin users (HR=0.83, CI=0.75-0.92), whereas after 10 years there was an
      increase in mortality (HR=1.94, CI=1.26-2.99). For NSAID use, no significant
      effect was observed on overall mortality (HR=1.07, CI=0.98-1.15). High-dose NSAID
      use was associated with a slight increase in mortality (HR=1.41, CI=1.26-1.56).
      INTERPRETATION: These findings provide further indication that aspirin may be
      beneficial in reducing mortality in colorectal cancer during the first 5 years.
      The same cannot be said for other NSAIDs, where a small increase in mortality was
      observed.

PMID- 23011485
TI  - Ethnic disparities in emergency department utilization patterns in southern
      Israel: a population-based study.
AB  - Approximately 520,000 residents (30 % Bedouins) inhabit the Negev region of
      southern Israel. Despite the geographical proximity, Bedouins differ from Jews
      demographically and socio-economically. To evaluate the ethnic disparities in
      emergency department (ED) utilization patterns in this population-based
      observational retrospective cohort study, individual data regarding 93,338 visits
      to the ED throughout 2007-2009 (9 months) were obtained. Demographic data were
      obtained from the Central Bureau of Statistics. The age- and gender-adjusted
      annual rates of ED visits were: 31.1 and 23 per 100 residents for Bedouins and
      Jews, respectively (P < 0.001). Significant differences in visiting patterns
      according to the weekday and time of day between these groups were observed.
      Bedouins were referred at a higher rate by a physician compared with Jews (81 vs.
      61 %; P < 0.001). Ethnic disparities in chief complaints including the following
      age-adjusted odds ratio values of Bedouins compared with Jews were found:
      respiratory [Adj OR 1.38 (95 % CI 1.31-1.46)], fever [Adj OR 0.67 (95 % CI 0.64
      0.71)], and cardiovascular [Adj OR 1.23 (95 % CI 1.16-1.32)] in Bedouins versus
      Jews, respectively (P < 0.001 each). Multivariate analysis demonstrated a higher
      risk for in-hospital admission among Bedouins than Jews [Adj OR 1.52 (95 % CI
      1.47-1.58); P < 0.001]. Utilization patterns of EDs of Bedouins and Jews differ.
      Potential etiologies are increased morbidity, reduced accessibility to primary
      care clinics, use of private often non-board-certified physicians, and decreased
      socio-economic status among Bedouins. This warrants further research and
      interventional programs dealing with causes of the disparities.

PMID- 23011486
TI  - Pulmonary cement emboli after kyphoplasty.

PMID- 23011487
TI  - Are depressive symptoms related to physical inactivity in chronic obstructive
      pulmonary disease?
AB  - PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) are
      physically inactive, and this predicts poor outcome. Factors influencing activity
      levels in COPD patients are poorly understood. Depression is common in COPD
      patients and may influence activity. Accordingly, in this pilot study, we
      evaluated the relationship between depressive symptoms and activity in clinically
      stable COPD (forced expiratory volume in 1 second [FEV(1)]/forced vital capacity
      < 0.70, FEV(1) < 80%). An additional inclusion criterion was the Hospital Anxiety
      and Depression Scale depression score, which had to be <=7 or >=10, representing
      low and high levels of depressive symptoms, respectively. METHODS: Sixteen
      patients with high depression scores (DEPR) and 20 with low depression scores
      (non-DEPR), were studied. Physical activity was measured over 7 consecutive days,
      using the SenseWear armband (BodyMedia Inc, Pittsburgh, PA) worn on the arm.
      RESULTS: The mean age was 69 +/- 9 years and the FEV(1) was 49 +/- 16%. The
      Hospital Anxiety and Depression Scale depression scores in DEPR and non-DEPR
      patients were 12.0 +/- 2.3 and 3.7 +/- 2.0, respectively. There were no
      significant between-group differences in age, gender, body mass index, FEV(1),
      supplemental oxygen requirement, and walk distance. DEPR and non-DEPR patients
      did not differ in estimated steps per day (3490 +/- 2020 vs 3634 +/- 2000; P =
      .83) or minutes per day, with activity >3 metabolic equivalents (11 +/- 7 vs 13
      +/- 9; P = .42). Steps correlated with the FEV(1) (r = 0.49; P = .002) and the 6
      minute walk distance (r = 0.69; P = .0001). CONCLUSIONS: We were unable to
      demonstrate a relationship between depressive symptoms and directly measured
      physical activity level in patients with COPD.

PMID- 23011488
TI  - Impact of peak oxygen uptake and muscular fitness on the performance of
      activities of daily living in patients with chronic obstructive pulmonary
      disease.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is a progressively
      debilitating disease, which, over time, may compromise patient ability to perform
      activities of daily living (ADL). The purpose of this study was to examine the
      relationships between selected parameters of physical fitness and performance of
      ADL in COPD patients. METHODS: A convenience sample of 23 COPD patients (11 men
      and 12 women, age 6869 years) was studied at the conclusion of an exercise
      rehabilitation program. Patients were assessed using the Continuous Scale
      Physical Functional Performance 10 Test (PFP-10) battery, chest press, leg press,
      and a symptom limited graded exercise test. RESULTS: The PFP-10 global score was
      54 +/- 12, and 11 patients fell below a global score of 57, which has been
      established as the threshold for independence. Peak oxygen uptake (VO(2peak)) was
      20 +/- 4 mL.kg(-1).min(-1), the forced expiratory volume in 1 second/forced
      expiratory volume ratio was 0.58 +/- 0.12, grip strength was 61 +/- 16 kg (both
      hands), and chest press and leg press were 4 +/- 3 and 12 +/- 7 kg/kg body
      weight, respectively. The associations between the PFP-10 VO(2peak) and leg press
      were modest (r = 0.501, P = .014; and r = 0.547, P = .008) as was grip strength
      (r = 0.418, P = .047). There was no association between the PFP-10 and forced
      expiratory volume, forced expiratory volume in 1 second/forced vital capacity, or
      chest press (r = -20.040, P = .856; r = 20.212, P = .330; and r = 0.120, P =
      .595), respectively. CONCLUSION: The results of this investigation suggest that
      lower body strength is important in optimizing ADL performance in COPD patients.

PMID- 23011490
TI  - Pediatric clear cell sarcoma of the kidney with atriocaval thrombus.
AB  - Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm that accounts for
      almost 3 % of pediatric renal tumors. Cavoatrial tumor thrombosis is very rare
      and because of poor response to chemotherapy, invasive surgical interventions
      such as open heart surgery may be indicated. A 6-year-old girl with CCSK of right
      kidney was treated with neoadjuvant chemotherapy. According to poor
      chemosensitivity, surgical intervention was planned. Right atriotomy was done,
      but intra-atrial part of tumor was very firm and unsuctionable; so the procedure
      was completed by laparotomy and en bloc resection of tumoral kidney and its
      cavoatrial extension through a limited venotomy on inferior vena cava. Although
      radical resection of CCSK with intracaval involvement should be considered as a
      multidisciplinary approach and intensive care and supports should be provided,
      atriocaval tumor in growth in CCSK is firm, non friable and non-adherent, and
      tumor en bloc resection may be possible through a limited venotomy via primary
      abdominal approach.

PMID- 23011489
TI  - Predictors of exercise intervention dropout in sedentary individuals with type 2
      diabetes.
AB  - PURPOSE: While the benefits of exercise in people with type 2 diabetes mellitus
      is well-known, knowledge of factors associated with dropouts of exercise
      intervention trials is limited. Examining clinical and psychosocial factors
      related to dropout is a necessary first step to developing an effective exercise
      program. We examined the predictors of a randomized trial of exercise
      intervention dropout among sedentary individuals with type 2 diabetes mellitus.
      METHODS: Participants (n = 140) were randomly allocated to a 6-month, 3 times per
      week exercise intervention, or to a control group. Psychological well-being was
      assessed using a 36-item Short Form Health Survey, the Profile of Mood States
      questionnaire, and an Exercise Self-Efficacy scale. Total percent body fat and
      abdominal subcutaneous and visceral fat were measured. Insulin resistance was
      assessed with the quantitative insulin sensitivity check index. Fitness was
      expressed as VO2 peak during treadmill testing. RESULTS: There were significantly
      more dropouts in the exercise group than in the control group (r = 20.220; P <
      .01). Those who dropped out of the study had less exercise self-efficacy for
      lifting weight (r = 0.187; P < .05). Physiological parameters associated with
      dropouts included low fitness (r = 0.255; P < .01), higher insulin resistance (r
      = 0.167; P < .05), higher total percent body fat (r = 20.213; P < .05), and
      higher subcutaneous abdominal fat (r = 20.220; P < .05). In the multiple logistic
      regression model, exercise group assignment, insulin resistance, and fitness
      remained significant predictors of dropouts. CONCLUSIONS: Special attention to
      the sedentary individuals with high insulin resistance and poor fitness should be
      incorporated into implementing exercise programs to improve diabetes treatment.

PMID- 23011491
TI  - Penetrating anorectal injuries in Jamaican children.
AB  - PURPOSE: To discuss the presentation, management and outcomes of penetrating
      anorectal injuries at the Bustamante Hospital for Children. METHODS: A
      retrospective review over an 11-year period (January 2001-December 2011) was
      undertaken. The data analysed were extracted from patients' case notes which were
      pulled based on the hospital's admission database. RESULTS: Over the study period
      a total of 14 children presented with penetrating anorectal injuries. The medical
      records for one child were missing. The mean age at presentation was 6 years.
      Impalement by a metal spike was the mechanism of injury in 12 children, with one
      case of sexual assault. Three of the children had associated urogenital injuries.
      Ten rectal injuries were extraperitoneal. Five of the 13 cases (38 %) were
      managed with a colostomy-average time to closure was 6 months. There was one case
      of perineal wound infection and dehiscence. There was no mortality. CONCLUSION:
      Selective fecal diversion in the form of a sigmoid loop colostomy is a safe and
      acceptable management option for children with penetrating anorectal injuries.
      The perineal wound itself can be closed primarily except in cases of delayed
      presentation.

PMID- 23011492
TI  - Development of the Italian version of the 42-item Chronic Pain Coping Inventory,
      CPCI-I: cross-cultural adaptation, factor analysis, reliability and validity.
AB  - PURPOSE: The aim of this study was to translate and adapt the Italian version of
      the Chronic Pain Coping Inventory (CPCI) and validate the translation in subjects
      with chronic non-specific pain of the locomotor system. METHODS: The
      questionnaire was developed following international recommendations. The
      psychometric analyses included factor analysis, reliability by internal
      consistency (Cronbach's alpha) and test-retest reliability (intraclass
      coefficient correlation, ICC), and construct validity by calculating the
      correlations between the subscales of the CPCI with measures of pain (numerical
      rating scale, NRS), disability (SIP-Roland Scale) and depression (CES-D)
      (Pearson's correlation). RESULTS: The CPCI was satisfactorily administered to 270
      subjects with chronic non-specific pain. Results of confirmatory factor analyses
      revealed that, of the CPCI-I 8 subscales, 6 demonstrated good data-model fit (CFI
      and NFI >= 0.90, RMSEA <= 0.08). Cronbach's alpha was satisfactory in all of the
      subscales (0.71-0.80); the ICCs were good/excellent in all of the subscales (0.80
      0.91). The correlations with the NRS, SIP-Roland and CES-D were poor in most
      cases as only the CPCI-Guarding subscale moderately correlated with disability (r
      = 0.31). CONCLUSION: The CPCI was successfully translated into Italian and proved
      to have a good factorial structure and psychometric properties similar to the
      original and adapted versions. The use of the Italian version of the CPCI is
      recommended for clinical and research purposes.

PMID- 23011493
TI  - The role of gender in the association of social capital, social support, and
      economic security with self-rated health among older adults in deprived
      communities in Beirut.
AB  - PURPOSE: To examine gender variations in the association of self-rated health
      (SRH) with social capital, social support, and economic security among older
      adults from three deprived communities in the suburbs of metropolitan Beirut.
      METHODS: A population-based cross-sectional study using the Older Adult Component
      of the Urban Health Survey. Face-to-face interviews were conducted with 328 older
      men and 412 older women aged 60 years and above. SRH was assessed by a single
      question and treated as a dichotomous outcome, and several indicators of social
      capital, social support, and economic security were examined as independent
      variables. RESULTS: Women were significantly more likely to report poor SRH
      compared to men (37.2 vs. 25.9 %, respectively). Better social capital indicators
      decreased significantly the odds of poor SRH among both men (OR = 0.76, 95 % CI:
      0.65-0.89) and women (OR = 0.71, 95 % CI: 0.62-0.82). Social support was strongly
      associated with SRH among women (OR = 0.56), but not among men (OR = 0.94). The
      reverse situation was observed for economic security (OR = 0.57 among men, OR =
      0.80 among women). CONCLUSIONS: In these deprived neighborhoods, social and
      economic factors may have gender-specific effects on the promotion of well-being
      among older adults, with social support being more salient to women's SRH and
      economic security being more salient to men's SRH. In health studies among older
      people, SRH captures not only social and physical health but also broader
      economic well-being.

PMID- 23011494
TI  - Impact of nocturnal calf cramping on quality of sleep and health-related quality
      of life.
AB  - PURPOSE: To evaluate the impact of nocturnal calf cramping (a condition that
      affects one in two people over 60 years of age) on quality of sleep and health
      related quality of life. METHODS: Eighty adults who experienced nocturnal calf
      cramp at least once per week and eighty age- and sex-matched controls who never
      experienced nocturnal cramp were recruited from the Greater Newcastle and Central
      Coast regions of New South Wales, Australia. All participants completed the SF
      36v2 and the Medical Outcomes Study Sleep Survey (MOS-SS). RESULTS: People who
      experienced nocturnal muscle cramps reported more sleep disturbance (p < 0.001),
      less adequate sleep (p = 0.001), less quantity of sleep (p = 0.02) and more
      snoring (p = 0.03). Both sleep problem summary indices for the MOS-SS identified
      people who experienced nocturnal muscle cramp as having more sleep problems than
      the controls. People who experienced nocturnal muscle cramps had lower health
      related quality of life for the SF-36 domains role physical (p = 0.007), bodily
      pain (p = 0.003) and general health (p = 0.02). SF-36 domains that primarily
      relate to mental health were not significantly different between groups. The
      impact of nocturnal calf cramps on health-related quality of life was largely
      explained by their negative impact on quality of sleep. CONCLUSIONS: Nocturnal
      calf muscle cramps are associated with substantially reduced quality of sleep and
      reduced physical aspects of health-related quality of life.

PMID- 23011495
TI  - An uncemented metal-backed glenoid component in total shoulder arthroplasty for
      osteoarthritis: factors affecting survival and outcome.
AB  - BACKGROUND: The reported survivorship of total shoulder replacement (TSR) is
      variable. This is probably related to implant design. We report the outcome and
      survivorship of the uncemented glenoid in patients with osteoarthritis receiving
      a TSR with an intact or repairable rotator cuff at surgery. METHODS: Thirty-two
      consecutive patients were analysed after TSR using a screw-fixed porous coated
      metal-back glenoid performed by a single surgeon, with a minimum follow-up of
      five years. Thirty-three TSRs in 32 patients (19 women) with a mean age of 67
      years were analysed, two of whom died before five years of follow-up. Thirty
      patients (31 shoulders) were monitored for a mean of 95 months (60-173 months).
      RESULTS: The Constant score improved by 22 points (p < 0.001). The only
      significant predictor of outcome on logistic regression analysis was the
      preoperative Constant score, with better scores resulting in a lesser improvement
      at last follow-up (p < 0.0001). Implant survivorship at ten years was 93 %. Three
      were revisions: two for polyethylene wear (both at six years) but with a well
      fixed glenoid, and another for loosening of the glenoid at 11 years
      postoperatively. Univariate analysis identified that younger age (56 year vs. 68
      years, p = 0.03) and a higher combined preoperative Constant score (35.7 vs.
      21.5, p = 0.03) were both predictors of failure. CONCLUSION: The uncemented
      glenoid performs well in the medium term for osteoarthritis of the shoulder in
      older patients, giving improved and sustained functional outcome. Age and
      preoperative level of function are predictors of outcome and survival.

PMID- 23011496
TI  - [Importance of encouraging scientific public-health research starting from the
      undergraduate level].

PMID- 23011497
TI  - Associations between physical activity, cardiorespiratory fitness, and obesity in
      Mexican children.
AB  - OBJECTIVE: To examine the independent relation of physical activity (PA) and
      cardiorespiratory fitness (fitness) with measures of obesity in Mexican children.
      MATERIALS AND METHODS: Children (N=193) in 5th and 6th grade from Guadalajara
      participated. Body mass index (BMI), sum of skinfolds (SS) and waist
      circumference (WC) were measured. PA was measured over four days using pedometry
      and fitness was measured using the 20 meter shuttle-run test. RESULTS: Fitness
      and PA were negatively related to the obesity measures in boys and girls (r=-0.57
      to -0.64 and r=-0.18 to -0.23 respectively). Age adjusted significant differences
      in WC, BMI, and SS were observed between the lowest and highest fitness tertiles
      for boys and girls (p<.01). Age, gender, and PA adjusted fitness explained 23 to
      34% of the variance on WC (r2=0.23, p<.01), BMI (r2=0.23, p<.01), and SS
      (r2=0.34, p<.01). CONCLUSION: Fitness is a stronger correlate and better
      predictor of obesity than PA in this sample.

PMID- 23011498
TI  - Compliance to micronutrient supplementation in children 3 to 24 months of age
      from a semi-rural community in Mexico.
AB  - OBJECTIVE: To identify associated factors to compliance for multiple
      micronutrient (MM) or iron and vitamin A (IVITA) supplementation, in children (3
      to 24 months old). MATERIALS AND METHODS: A database (n=465 children) from a
      randomized, controlled, clinical trial, carried out in a semi-rural setting in
      Mexico, was analyzed. The compliance rate of MM and IVITA supplements was
      calculated. Adequate compliance rate (AC>80%), and its association with children
      and households characteristics, was determined. RESULTS: The compliance mean was
      high (MM:78.2%, IVITA:80.1%; p<0.05). The odds of AC were 59% greater in the
      children of IVITA than with MM group, although the estimate was only marginally
      significant (p=0.052). Maternal education (p<0.001), child birth weight
      (p=0.003), and children with cough (p<0.001) or fever (p=0.024) were
      significantly associated with AC and significantly marginal was maternal
      indigenous (p=0.071). CONCLUSION: The high AC was consistent with others efficacy
      studies. More research is needed to document physiological, cultural, social and
      operative factors affecting compliance with supplementation.

PMID- 23011499
TI  - [Development of a didactic questionnaire to measure vegetable and fruit intake
      during the school recess. Pilot test].
AB  - OBJECTIVE: To develop an open, self-reported questionnaire, focused in
      understanding intake and intention to increase vegetable and fruit consumption
      during the Mexican children's lunchtime. MATERIALS AND METHODS: After assessing
      pilot tests, the self-reported questionnaire was applied as a classroom exercise
      to measure children's consumptions of fruit and vegetables. RESULTS: A total of
      486 children completed the questionnaire (49.8% males and 50.2% females). The
      reported food consumption indicates that 24.5% of children do not consume
      vegetables or fruits, and among consumers the most common portion size is one.
      Girls consume more vegetables and fruits and they can recognize more benefits. A
      total of 9.7% of the participants that do not consume VF, expressed less
      intention of including vegetables or fruits in their lunch. These results were
      similar to those reported by other authors. CONCLUSION: This study is useful to
      identify strengths and limitations during the design and implementation of this
      type of instrument to understand children's food habits during school recess.

PMID- 23011501
TI  - Facility-based care for delivery and management of complications related to
      pregnancy and childbirth in Mexico.
AB  - OBJECTIVE: To describe the incidence and management of severe maternal and
      newborn complications in selected health facilities in Mexico. MATERIALS AND
      METHODS: As part of the WHO Multicountry Survey on Maternal and Newborn health,
      information was collected from medical records of women with deliveries and/or
      severe maternal complications during pregnancy or puerperium in 14 hospitals in
      Mexico City and the state of Guanajuato, Mexico. RESULTS: Of 13 311 women, 157
      (12 per 1 000 live births) had severe maternal complications including 4 maternal
      deaths. The most frequent complications were preeclampsia, postpartum hemorrhage,
      and chronic hypertension. Adverse perinatal outcomes were more frequent among
      women with severe maternal complications. A high use of uterotonics and
      parenteral antibiotics was found. A small proportion of women with eclampsia
      received magnesium sulfate. CONCLUSION: This study provides indicators on the
      incidence and management of maternal and neonatal complications in Mexico, which
      may be useful in studying and evaluating the performance of obstetric services.

PMID- 23011500
TI  - Older adults under a mixed regime of infectious and chronic diseases.
AB  - OBJECTIVE: Analyze the impact of a mixed regime of infectious and chronic
      conditions among older adults in Mexico on their health progression. MATERIALS
      AND METHODS: A total of 12 207 adults from the Mexican Health and Aging Study
      were included. Logistic regression analyses were conducted to assess the
      relationship between self-reported health (SRH) and covariates, including
      infectious and chronic diseases. Changes in SRH between 2001-2003 were analyzed
      using multinomial analysis. RESULTS: Older age, low SES, poor SRH and type of
      disease at baseline increase the odds of poor SRH at follow-up. Odds of poor SRH
      are highest for persons with both types of diseases (OR 2.63, SE 0.24), followed
      by only chronic (OR 1.86; SE 0.12) and finally only infectious (OR 1.55; SE
      0.25). CONCLUSION: Mexico is experiencing a mixed regime of diseases that affects
      the health and well-being of older adults. Despite the rising importance of
      chronic diseases in countries like Mexico, it is premature to disregard the
      relevance of infectious diseases for public health.

PMID- 23011502
TI  - High prevalence of late diagnosis of HIV in Mexico during the HAART era.
AB  - OBJECTIVE: To evaluate the prevalence of late HIV diagnosis (CD4<200 cell/mm3) in
      an HIV clinic in Mexico City between 2001-2008, to assess changes in this
      prevalence across the study period, and to determine the risk factors associated
      to late testing (LT). MATERIALS AND METHODS: Cross-sectional analysis including
      all patients recently diagnosed as HIV. We estimated the proportion of LT
      patients and compared demographic characteristics between those and all other. We
      determine the risk factors associated to LT using logistic regression methods.
      RESULTS: Sixty one percent of LT patients present when are diagnosed for the
      first time. The prevalence did not decrease between 2001 and 2008 (p=0.37). Older
      age (OR: 2.4; 95%CI 1.2-4.7), unemployment (OR: 1.75; 95%CI 1.12-2.75) and less
      than nine years of education (OR: 2.44; 95%CI 1.37-4.33) were independently
      associated to LT, in a multivariate analysis. CONCLUSION: LT has high prevalence
      in Mexico, this impact on antiretroviral effectiveness and perhaps on HIV
      transmission. Policies for HIV-prevention in Mexico need to be modified to reduce
      LT prevalence including more aggressive strategies of testing.

PMID- 23011503
TI  - [HPV vaccine acceptability and knowledge among gynecologists in Argentina].
AB  - OBJECTIVE: To evaluate HPV vaccine acceptability and prescription; knowledge
      about HPV vaccine; and knowledge about HPV infection and cervical cancer among
      Argentinean gynecologists. MATERIALS AND METHODS: Between November 2009 and March
      2010 we carried out an internet survey of 686 gynecologists. RESULTS: More than
      80% of gynecologists prescribed HPV vaccine, knew characteristics of HPV
      vaccines, and knew that women will still need regular cervical cancer screening
      after HPV vaccination; 37% had global knowledge about relationship between
      vaccine, detection and treatment of cervical cancer; 25% underestimated the
      epidemiological extent of HPV infections, ~30% was not aware of the causative
      relationship between HPV infection and cervical cancer and ~40% had global
      knowledge about management of HPV infection. CONCLUSIONS: HPV vaccine
      acceptability is high. Physicians need to be fully informed on HPV vaccination
      and cervical cancer as well as HPV infection management.

PMID- 23011504
TI  - [Malaria's seroepidemiology in a group of migrants in transit (Chiapas, 2008)].
AB  - OBJECTIVE: To know the prevalence of malaria and the factors associated with the
      infection in migrants in the southern border of Mexico, during 2008. MATERIALS
      AND METHODS: In 706 migrants, active malaria infection was investigated using a
      rapid diagnostic test and PCR and past infection using serology. A questionnaire
      was applied to investigate the conditions associated to infection. RESULTS: 85.6%
      originated from Central America, none presented an active infection, although
      4.2% were seropositive, most of these came from the countries with the highest
      malaria incidence in the region. Seropositivity was associated with the number of
      previous malaria episodes (OR=1.44; IC95% 1.04-2.00), years living in their
      community of origin (OR=1.03; IC95% 1.00-1.07), and knowledge and self-medication
      with anti-malaria drugs (OR=3.38; IC95% 1.48-7.67). CONCLUSIONS: . The previous
      exposure of migrants and the difficulties for their detection indicate the need
      of new strategies for the epidemiological surveillance for these populations.

PMID- 23011505
TI  - [Human leptospirosis diagnosis:macroscopic agglutination test evaluation in
      different stages of the disease].
AB  - OBJECTIVE: To evaluate the macroscopic agglutination test using Temperature
      Resistant (TR) antigen as a screening test for the diagnosis of human
      leptospirosis in different stages of the disease. MATERIALS AND METHODS: The
      criteria for case definition were based on the results of the microscopic
      agglutination test (MAT), leukocyte counts and neutrophilia, resulting 218
      confirmed cases and 242 non- cases. Each sample was classified according to the
      days of the disease progression in three stages: first (<10 days), second (10 -
      25 days) and third (> 25 days). The design was cross-sectional observational.
      RESULTS: TR sensitivity was 71,1% on stage 1. 93.4% on stage 2 and 95.6% on stage
      3. The specificity at different stages ranged from 79.0 to 69.2%. Intra and inter
      operator variability was moderate. CONCLUSION: TR variability, low sensitivity in
      the first stage and low specificity found in all stages of the disease, suggest
      that it is essential to incorporate new diagnostic methods to screen for early
      detection of cases in our country and in countries that still apply such methods.

PMID- 23011506
TI  - [Towards the eradication of poliomyelitis: Mexico's achievements and challenges].
AB  - Since the strategies to eradicate polio were implemented, the incidence of
      paralytic polio has dropped dramatically. Four main strategies have greatly
      contributed: a) High immunization coverage rate with oral polio vaccine (OPV), b)
      Supplementary immunization activities during the National Immunizations Days c)
      An effective epidemiological surveillance system for acute flaccid paralysis
      (AFP) and d) Intensified immunization activities in high risk areas. Three
      countries remain polio endemic, nevertheless, any country has a potential risk of
      the virus importation from one of these endemic areas; an accidental release of
      poliovirus from a research or clinical laboratory, or from having a circulating
      vaccine-derived poliovirus in the environment. The present document aims to
      provide an historical background that made possible the disease elimination in
      Mexico. Moreover, we discuss the challenges that every country needs to face in
      order to achieve a polio-free world.

PMID- 23011508
TI  - Comparing attendees with non-attendees in breast screening does not provide
      useful information about an effect on prognostic features or mortality.

PMID- 23011512
TI  - Shear-induced gelation of soft strawberry-like particles in the presence of
      polymeric P(BA-b-AA) surfactants.
AB  - The effect of polymeric surfactants, copolymers of n-butyl acrylate (BA) and
      acrylic acid (AA), on shear-induced gelation of a colloidal system in the absence
      of additional electrolytes is studied. One random (PBA-co-PAA) and two block
      copolymer (PBA-b-PAA, with different PAA lengths) surfactants have been
      synthesized by ATRP and used in this work. The colloidal system is composed of
      strawberry-like particles with a rubbery core, partially covered by a few grafted
      plastic patches. In the absence of any surfactant, as the colloidal system passes
      through a microchannel at a Peclet number of 220 and a particle volume fraction
      of 0.15, shear-induced gelation occurs and the particles coalesce partially, due
      to the rubbery core, leading to a fractal dimension of the clusters constituting
      the gel equal to 2.78. On the other hand, in the presence of any of the three
      polymeric surfactants, shear-induced gelation occurs only in the range of low
      surfactant surface density. Meanwhile, the fractal dimension of the clusters
      decreases with adsorption of the two block surfactants, reaching a plateau value
      of about 2.58, while for the random surfactant it remains constant and equal to
      2.78, like in the absence of any surfactant. This indicates that adsorption of
      the block surfactants can reduce the particle coalescence, while adsorption of
      the random surfactant cannot. Moreover, for all three surfactants, as their
      surface density increases progressively, a transition from solid-like gel to a
      liquid-like state occurs and finally no shear-induced gelation or even
      aggregation occurs. Since the three surfactants comprise carboxylic groups,
      considering also the results in the literature (Zaccone et al., J. Phys. Chem. B,
      2008, 112, 1976; 6793), we can reach a general conclusion that carboxylic groups
      on the particle surface not only stabilize the particles through electrostatic
      repulsion, but also generate very short-range, strongly repulsive (e.g.
      hydration, steric) forces, which when high enough protect the particles from
      intense shear-activated aggregation.

PMID- 23011510
TI  - Ratiometric fluorescence chemodosimeters for fluoride anion based on pyrene
      excimer/monomer transformation.
AB  - Two pyrene dimers containing an -O-Si-Si-O- or -O-Si-O- linkage have been
      designed which exhibit ratiometric excimer/monomer emission upon fluoride anion
      induced Si-O bond cleavage. Incorporation of the probe into water soluble
      polymeric nanoparticles enhances its intracellular uptake and displays
      ratiometric fluorescent sensing for F(-) in living cells.

PMID- 23011513
TI  - Do chimpanzees (Pan troglodytes schweinfurthii) exhibit sleep related behaviors
      that minimize exposure to parasitic arthropods? A preliminary report on the
      possible anti-vector function of chimpanzee sleeping platforms.
AB  - Great apes spend half of their lives in a nightly "nest" or sleeping platform
      (SP), a complex object created by modifying foliage, which functions as a stable
      substrate on which to sleep. Of the several purported functions of SPs, one
      hypothesis is that they protect against parasitic infection. Here we investigate
      the role of SP site choice in avoiding molestation by arthropods. This study
      presents preliminary data on the insect-repellent properties of preferred
      sleeping tree species Cynometra alexandri. Insect traps were deployed in gallery
      forest habitats in which chimpanzees typically "nest." We compared traps placed
      adjacent to SPs artificially manufactured with C. alexandri trees to an open area
      within the same habitat. Multiple measures of arthropod counts indicate that
      simulated C. alexandri SP sites have fewer arthropods than similar non-SP sites.
      Volatile compounds secreted by C. alexandri foliage are hypothesized to repel
      annoying arthropods and/or mask chimpanzee olfactory signals. Of the total
      insects captured (n = 6,318), n = 145 were mosquitoes. Of the total mosquitoes
      captured, n = 47 were identified as Anopheles (female, n = 12). The prominent
      malarial vector Anopheles gambiae was identified among the captured mosquito
      sample. These results suggest that the presence of broken branches of the tree
      species C. alexandri reduce the amount of insects a chimpanzee is exposed to
      throughout a night's sleep. This great ape behavioral and socio-technological
      adaptation may have evolved, in part, to increase quality of sleep as well as
      decrease exposure to vectors of disease.

PMID- 23011515
TI  - Photo-induced oxidation of [Fe(II)(N4Py)CH3CN] and related complexes.
AB  - The photochemistry of the complexes [Fe(N4Py)(CH(3)CN)](ClO(4))(2) (1), where
      N4Py is 1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine and
      [Fe(MeN4Py)(CH(3)CN)](ClO(4))(2) (2), where MeN4Py is 1,1-di(pyridin-2-yl)-N,N
      bis(pyridin-2-ylmethyl)ethanamine, in water, dichloromethane and methanol is
      described. Under UV or visible irradiation both 1 and 2 undergo enhancement of
      the rate of outer sphere electron transfer to (3)O(2) to yield the superoxide
      radical anion and the complexes in the Fe(III) redox state. Addition of ascorbic
      acid to the photoproduct leads to a recovery of the initial UV/Vis spectrum of 1
      and 2, indicating that ligand oxidation does not occur. The results are discussed
      within the context of the recent report of the enhancement of the oxidative DNA
      cleavage activity of 1 under UV and visible irradiation (Inorg. Chem. 2010, 49,
      11009).

PMID- 23011509
TI  - Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow
      up study of BRCA2 mutation carriers.
AB  - Several common germline variants identified through genome-wide association
      studies of breast cancer risk in the general population have recently been shown
      to be associated with breast cancer risk for BRCA1 and/or BRCA2 mutation
      carriers. When combined, these variants can identify marked differences in the
      absolute risk of developing breast cancer for mutation carriers, suggesting that
      additional modifier loci may further enhance individual risk assessment for BRCA1
      and BRCA2 mutation carriers. Recently, a common variant on 6p22 (rs9393597) was
      found to be associated with increased breast cancer risk for BRCA2 mutation
      carriers [hazard ratio (HR) = 1.55, 95 % confidence interval (CI) 1.25-1.92, p =
      6.0 * 10(-5)]. This observation was based on data from GWAS studies in which,
      despite statistical correction for multiple comparisons, the possibility of false
      discovery remains a concern. Here, we report on an analysis of this variant in an
      additional 6,165 BRCA1 and 3,900 BRCA2 mutation carriers from the Consortium of
      Investigators of Modifiers of BRCA1/2 (CIMBA). In this replication analysis,
      rs9393597 was not associated with breast cancer risk for BRCA2 mutation carriers
      (HR = 1.09, 95 % CI 0.96-1.24, p = 0.18). No association with ovarian cancer risk
      for BRCA1 or BRCA2 mutation carriers or with breast cancer risk for BRCA1
      mutation carriers was observed. This follow-up study suggests that, contrary to
      our initial report, this variant is not associated with breast cancer risk among
      individuals with germline BRCA2 mutations.

PMID- 23011517
TI  - Community variation in adolescent access to indoor tanning facilities.
AB  - Melanoma rates among younger women in New Hampshire (NH) are rising. In urban
      studies, youth proximity to tanning facilities has been linked to indoor tanning,
      a proven cause of melanoma. Youth access has not been examined in rural settings.
      To determine on a statewide basis the influence of rurality and community income
      level on female students' ease of access to tanning facilities, all NH tanning
      facilities (N = 261) and high schools (N = 77) in 2011 were spatially and
      statistically analyzed to determine schools with more facilities within 2 miles
      of the school and greater capacity (fewer female students per facility), for
      indoor tanning. Schools above the state-wide average for both measures were
      classified as "Easy Access" to indoor tanning. Among NH high schools, 74 % have 1
      or more tanning facility within two miles and 22 % have "Easy Access" to tanning
      facilities. Ease of access did not differ by rurality. Lower-income school status
      was an independent predictor of both greater capacity and "Easy Access". While
      urban and rural teens have similar access to indoor tanning, female students in
      lower-income communities have easier access. Variations in access by community
      size and income must be considered in planning interventions to address youth
      indoor tanning.

PMID- 23011516
TI  - Interactions of tumour-targeting nanoparticles with proteins: potential of using
      capillary electrophoresis as a direct probe.
AB  - Metal-based nanoscale particles possess unique optoelectronic or magnetic
      properties that make them highly promising as imaging agents in cancer therapy
      research. The fate of nanoparticles in vivo and particularly, the delivery to
      tumours are closely related to their interactions with plasma proteins.
      Furthermore, proteins can be used to modify the nanoparticle surface in order to
      facilitate active targeting to tumours. Therefore, there is an ongoing need for
      new and more capable analytical methodologies to characterize the protein
      nanoparticle binding. Due to the small-sample volume requirement, high degree of
      resolution and, most importantly, mild, species-friendly separation conditions,
      capillary electrophoresis (CE) is gaining increasing popularity in the analysis
      of protein-nanoparticle interaction. This perspective article highlights the
      potential of CE in studying reactions associated with protein-mediated
      transformations of nanoparticles, with the focus on quantum dots, gold and iron
      oxide nanoparticles. Different ways by which CE can be applied to such monitoring
      are summarized and critically assessed using a representative coverage of recent
      publications.

PMID- 23011518
TI  - Periodic appearance and disappearance of a chest wall (serratus anterior
      development) cavernous hemangioma that was finally resected in a child.
AB  - Primary chest wall tumors occur infrequently; in particular, cavernous hemangioma
      of the chest wall is an extremely rare disease. We report a case of child with
      cavernous hemangioma of the chest wall, which was successfully resected. Obvious
      enlargement of the tumor and the appearance of pain were observed during a 2-year
      follow-up. In the present case, transcutaneous ultrasonography showed the
      appearance and disappearance of the mass. This was considered to be caused by the
      transfer of contents between the shallow and deep parts of the tumor. This may
      have resulted from serratus anterior muscle movement between the two-layered
      tumor. Transcutaneous ultrasonography, as well as magnetic resonance imaging, was
      therefore extremely effective for preoperative diagnosis. Transcutaneous
      ultrasonography is easily performed, even in children, such as in the present
      case. Because of its simplicity and usefulness, transcutaneous ultrasonography
      may be considered as the first-line imaging modality for diagnosis. 

PMID- 23011519
TI  - Pulmonary vascular disease associated with pulmonary hypertension in 445
      patients: diagnosis from lung biopsy and autopsy.
AB  - PURPOSE: Diagnosis from lung biopsy or autopsy was performed in 445 patients with
      congenital (385) or acquired (60) heart disease from all over Japan. The purpose
      of this study is the presentation of these prospective data collections. METHODS:
      Of the patients with congenital heart disease, 354 were biopsied to determine
      whether surgery was indicated. Decisions regarding surgery were based on the
      index of pulmonary vascular disease in simple cardiac anomalies or
      atrioventricular septal defects (AVSD). In total anomalous pulmonary venous
      connection (TAPVC), operative indication was determined by the degree of
      hypoplasia of small pulmonary arteries. Operability of Fontan procedure was based
      on the degree of residual medial hypertrophy after pulmonary artery banding.
      RESULTS: In patients with simple cardiac anomalies, radical surgery was indicated
      in 166. Radical surgery was indicated in 50 patients with AVSD. In 26 patients
      with TAPVC, radical surgery was not indicated in 10. In 68 Fontan candidates,
      surgery was not indicated in 49. Among 7 patients with tetralogy of Fallot, 1 was
      not a surgical candidate. Of the 60 acquired heart disease patients, 16 had
      idiopathic pulmonary arterial hypertension and 36 had chronic thromboembolic
      pulmonary hypertension. In 6 patients, lung biopsy revealed pulmonary veno
      occlusive disease; 2 patients had combined valvular disease. CONCLUSION: The
      cardiac surgeon, pediatric cardiologist, and cardiologist who requested diagnosis
      from lung biopsy or autopsy were gratified with the results.

PMID- 23011520
TI  - Unknown primary large cell neuroendocrine carcinoma (LCNEC) in the mediastinum.
AB  - Unknown primary large cell neuroendocrine carcinoma (LCNEC) in the mediastinum is
      extremely rare. In this report, we present a case of a 53-year-old man with
      superior vena cava (SVC) syndrome who developed LCNEC in the middle mediastinum.
      His chief complaint was facial edema. Chest X-ray revealed an abnormal shadow in
      the right upper mediastinum. Computed tomography (CT) scan of the chest revealed
      a 67-mm mass in the middle mediastinum. Tumor invasion caused constriction of the
      SVC. The patient underwent induction chemoradiotherapy with vinorelbin and
      cisplatin and concurrent radiation therapy. After induction therapy, the tumor
      size decreased remarkably and was resected completely. The pathological diagnosis
      was LCNEC. 

PMID- 23011521
TI  - Contemporary reviews by surgeon: timing of operation for chronic aortic
      regurgitation.
AB  - The timing of operation for severe chronic and asymptomatic aortic regurgitation
      remains problematic, though the present trend is to prefer early surgery. In this
      article, we review recent reports, mainly published after 2006, regarding
      indications for surgical treatment for pure chronic AR.

PMID- 23011522
TI  - Sweets consumption of preschool children--extent, context, and consumption
      patterns.
AB  - OBJECTIVES: Sweets consumption is one of the risk factors of caries, especially
      among children. The aim of our study was to explore the extent and context of
      preschoolers' sweets consumption and to identify high-risk groups. MATERIALS AND
      METHODS: The baseline cross-sectional data used originated from a nutritional
      intervention study encompassing 879 parental surveys, which were obtained in 52
      kindergartens in Baden-Wurttemberg-the third largest federal state in Germany
      between September and March 2009. Our outcome variable "sweets consumption" was
      operationalized using food-frequency items and analyzed by testing the influence
      of sociodemographic, educational, cultural, and family context covariates.
      RESULTS: Most preschoolers consumed sweets every day-on average 9.7 +/- 6.2 times
      per week. Most popular were cookies, gummy bears, and chocolate. Sweets
      consumption did not correlate significantly with sociodemographic factors like
      age and sex but rather was associated with cultural and contextual factors such
      as immigrant background, parental education, specific nutritional knowledge
      levels, and access arrangements in the home. CONCLUSIONS: The consumption
      patterns identified are a result of high availability and parental influence
      (factors such as parents' knowledge levels, interest in, and habits regarding
      their child's nutrition). CLINICAL RELEVANCE: Dental practitioners should place
      more emphasis on gathering information from young patients regarding excessive
      and frequent consumption of sweets and consequently on trying to educate the
      children and their parents on oral health risks associated with such consumption.
      Particular attention is to be paid to children of Turkish and Arabic decent, as
      they have been shown to consume above-average amounts of sweets.

PMID- 23011523
TI  - Mesiodistal tooth size in non-syndromic unilateral cleft lip and palate patients:
      a meta-analysis.
AB  - OBJECTIVES: To evaluate, using meta-analysis methodology, mesiodistal tooth
      dimensions in non-syndromic unilateral cleft lip and palate (CLP) patients.
      MATERIALS AND METHODS: A literature search was conducted using PubMed, Medline,
      Google Scholar Beta, EMBASE Excerpta Medica, CINAHL, Web of Science, and the
      Cochrane Collaboration, identifying English and non-English articles reporting on
      mesiodistal tooth dimensions on the cleft and non-cleft side of non-syndromic
      unilateral CLP patients. Additional studies were identified by searching
      reference lists of articles consulted. Only studies with a suitable control group
      were included. Two examiners independently performed the literature search and
      data extraction. Using meta-analysis software, data extracted from each selected
      study were statistically combined using the fixed-effects model. Weighted mean
      differences, 95 % confidence intervals, and heterogeneity were calculated for
      each measurement. RESULTS: Four articles fulfilling the inclusion criteria were
      located and included in the meta-analysis. Maxillary incisors and first molars
      were found to be significantly larger on the non-cleft side while mandibular
      incisors and premolars were larger on the cleft side, in non-syndromic unilateral
      CLP patients. On the cleft side, maxillary premolars and second molars were
      larger in cleft than control patients while incisors were smaller, whereas all
      mandibular teeth were larger in cleft patients. On the non-cleft side, all
      maxillary teeth except for the central incisors were larger in the cleft than
      control patients, while all mandibular teeth were larger in the cleft patients
      except for lateral incisors. CONCLUSIONS: Non-syndromic unilateral CLP patients
      tend to have larger posterior but smaller anterior teeth compared with the
      general population. Comparing sides, unilateral CLP patients tend to have smaller
      maxillary but larger mandibular teeth on the cleft than on the non-cleft side.
      CLINICAL RELEVANCE: Given that obtaining a stable, functional, and esthetic
      occlusion requires a thorough evaluation of tooth size, knowledge about trends in
      tooth size variations in CLP patients can help with dental and orthodontic
      treatment planning.

PMID- 23011524
TI  - Cytotoxicity test of dentin bonding agents using millipore filters as dentin
      substitutes in a dentin barrier test.
AB  - OBJECTIVES: The purpose of this study was to find proper dentin substitute for
      standardized dentin barrier test and perform the cytotoxicity test of commercial
      bonding agents with the proper substitute. MATERIALS AND METHODS: The three
      dimensional cells attached to dentin disc or millipore filters as the dentin
      substitute were tested in a dentin barrier test by perfusion. MTT assay was
      performed as an evaluation method for the cell survival rate. The cytotoxicity
      test of serial phenol dilution by bovine dentin disc was done to determine a
      standard toxic material, and the test of this proper phenol by using various
      millipore combinations was performed to find the suitable dentin substitute.
      Also, the cytotoxicity test of bonding agents was performed by this standardized
      substitute. The cell viability was expressed as percentages of untreated group.
      RESULTS: Phenol concentration of 0.05 % was selected as the standard toxic
      material. The different combinations of millipore filters--two sheets of 0.45
      MUm, two sheets of 0.22 MUm, and the combination of 0.65, 0.45, and 0.22 MUm-
      showed similar cytotoxicity to natural dentin discs by 0.05 % phenol (p > 0.05).
      The millipore combination of 0.65, 0.45, and 0.22 MUm that had structural
      similarity to natural dentin discs was used as the substitute for cytotoxicity
      test of bonding agents. The toxic level of Adper Prompt L-Pop using the selected
      substitute was significantly the highest among four kinds of dentin bonding
      agents (p < 0.05). Also, the dentin barrier test by the substitute showed
      constant results compared with the one by the natural dentin disc. CONCLUSIONS:
      The millipore filter combination of 0.65, 0.45, and 0.22 MUm could be used as the
      substitute for the cytotoxicity test of materials applied to dentin. CLINICAL
      RELEVANCE: Dentin barrier test by standardized substitutes would be helpful for
      considering the potential toxicity of dentin bonding agents prior to clinical
      adaptations and reducing the variations of natural bovine dentin that has
      individually different characteristics.

PMID- 23011525
TI  - Cardiovascular outcomes in hypertensive patients:  comparing single-agent therapy
      with combination therapy.
AB  - OBJECTIVES: To determine whether blood pressure (BP) control in hypertensive
      patients achieved with combination drug therapy provides the same cardiovascular
      benefits as with single-agent therapy. BACKGROUND: Drug combinations, most often
      including hydrochlorothiazide (HCTZ), are now recommended for routine BP
      management, but their effects on cardiovascular event rates have not been
      compared with effective monotherapy. METHODS: We conducted retrospective analyses
      of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) data. VALUE
      compared cardiovascular event rates of valsartan and amlodipine. Patients with
      BPs not controlled (<140/90  mmHg) by the single agents had HCTZ and, if
      required, additional drugs of different classes, added. Using data pooled from
      the two treatment arms, we have now divided patients into those controlled on
      monotherapy and those controlled or not controlled by combination therapy. The
      primary study endpoint was first occurrence of cardiovascular death or nonfatal
      myocardial infarction or stroke. Comparisons between groups were by Cox
      regression, adjusted for on-treatment BP, age, prior cardiovascular events and
      left ventricular hypertrophy; the comparison between the monotherapy and
      combination therapy controlled groups was based on events occurring after 3
      months by when the decision to use monotherapy or combination therapy was made.
      RESULTS: The primary endpoint occurred in 505 of 5924 (8.5%) monotherapy and 511
      of 4621 (11.1%) combination therapy controlled patients: hazard ratio was 0.80
      [95% confidence interval (CI) 0.70-0.90]. If these two groups were matched for
      baseline BPs and all events included from study baseline, the hazard ratio was
      0.76 (95% CI 0.67-0.86). The difference between combination controlled and
      uncontrolled [434 of 3390 (12.8%)] groups was not significant [hazard ratio 0.90
      (95% CI 0.80-1.03], nor when they were matched for baseline BPs [hazard ratio
      0.95 (95% CI 0.81-1.11)]. CONCLUSION: Independent of prior cardiovascular history
      or baseline BP, hypertensive patients requiring combination therapy, which
      includes a thiazide diuretic for BP control, have a poorer cardiovascular
      prognosis than those controlled by monotherapy and only a nonsignificantly lower
      event rate than noncontrolled patients.

PMID- 23011526
TI  - Spironolactone, eplerenone and the new aldosterone blockers in endocrine and
      primary hypertension.
AB  - Mineralocorticoid receptor antagonists (MRAs) are commonly used to reduce blood
      pressure, left-ventricular hypertrophy, and urinary albumin excretion in patients
      with essential hypertension or primary aldosteronism. Effects of MRAs on
      hypertensive organ damage seem to occur beyond what is expected from the mere
      reduction of blood pressure. This suggests that activation of the
      mineralocorticoid receptor plays a central role in the development of cardiac and
      renal abnormalities in hypertensive patients. However, broad use of classic MRAs
      such as spironolactone has been limited by significant incidence of gynecomastia
      and other sex-related adverse effects. To overcome these problems, new
      aldosterone blockers have been developed with different strategies that include
      use of nonsteroidal MRAs and inhibition of aldosterone synthesis. Both strategies
      have been designed to avoid the steroid receptor cross-reactivity of classic MRAs
      that accounts for most adverse effects. Moreover, inhibition of aldosterone
      synthesis could have an additional benefit due to blockade of the
      mineralocorticoid receptor-independent pathways that might account for some of
      the untoward effects of aldosterone. The new aldosterone blockers are currently
      having extensive preclinical evaluation, and one of these compounds has passed
      phase 2 trials showing promising results in patients with primary hypertension
      and primary aldosteronism. This narrative review summarizes the knowledge on the
      use of classic MRAs in hypertension and covers the evidence currently available
      on new aldosterone blockers.

PMID- 23011528
TI  - Mortality and long-term functional outcome associated with intracranial pressure
      after traumatic brain injury.
AB  - PURPOSE: Elevated intracranial pressure (ICP) has been associated with increased
      mortality in patients with severe traumatic brain injury (TBI). We have examined
      whether raised ICP is independently associated with mortality, functional status
      and neuropsychological functioning in adult TBI patients. METHODS: Data from a
      randomized trial of 499 participants were secondarily analyzed. The primary
      endpoints were mortality and a composite measure of functional status and
      neuropsychological function (memory, speed of information processing, executive
      function) over a 6-month period. The area under the curve of the ICP profile
      (average ICP) during the first 48 h of monitoring was the main predictor of
      interest. Multivariable regression was used to adjust for a priori defined
      confounders: age, Glasgow Coma Score, Abbreviated Injury Scale-head and hypoxia.
      RESULTS: Of the participants, 365 patients had complete 48-h ICP data. The
      overall 6-month mortality was 18 %. The adjusted odds ratio of mortality
      comparing 10-mmHg increases in average ICP was 3.12 (95 % confidence interval
      1.79, 5.44; p < 0.01). Overall, higher average ICP was associated with decreased
      functional status and neuropsychological functioning (p < 0.01). Importantly,
      among survivors, increasing average ICP was not independently associated with
      worse performance on neuropsychological testing (p = 0.46). CONCLUSIONS: Average
      ICP in the first 48 h of monitoring was an independent predictor of mortality and
      of a composite endpoint of functional and neuropsychological outcome at the 6
      month follow-up in moderate or severe TBI patients. However, there was no
      association between average ICP and neuropsychological functioning among
      survivors.

PMID- 23011529
TI  - An optimized set-up for helmet noninvasive ventilation improves pressure support
      delivery and patient-ventilator interaction.
AB  - OBJECTIVE: To test the effects on mechanical performance of helmet noninvasive
      ventilation (NIV) of an optimized set-up concerning the ventilator settings, the
      ventilator circuit and the helmet itself. SUBJECTS AND METHODS: In a bench study,
      helmet NIV was applied to a physical model. Pressurization and depressurization
      rates and minute ventilation (MV) were measured under 24 conditions including
      pressure support of 10 or 20 cm H(2)O, positive end expiratory pressure (PEEP) of
      5 or 10 cm H(2)O, ventilator circuit with "high", "intermediate" or "low"
      resistance, and cushion deflated or inflated. In a clinical study pressurization
      and depressurization rates, MV and patient-ventilator interactions were compared
      in six patients with acute respiratory failure during conventional versus an
      "optimized" set-up (PEEP increased to 10 cm H(2)O, low resistance circuit and
      cushion inflated). RESULTS: In the bench study, all adjustments simultaneously
      applied (increased PEEP, inflated cushion and low resistance circuit) increased
      pressurization rate (46.7 +/- 2.8 vs. 28.3 +/- 0.6 %, p < 0.05), depressurization
      rate (82.9 +/- 1.9 vs. 59.8 +/- 1.1 %, p <= 0.05) and patient MV (8.5 +/- 3.2 vs.
      7.4 +/- 2.8 l/min, p < 0.05), and decreased leaks (17.4 +/- 6.0 vs. 33.6 +/- 6.0
      %, p < 0.05) compared to the basal set-up. In the clinical study, the optimized
      set-up increased pressurization rate (51.0 +/- 3.5 vs. 30.8 +/- 6.9 %, p <
      0.002), depressurization rate (48.2 +/- 3.3 vs. 34.2 +/- 4.6 %, p < 0.0001) and
      total MV (27.7 +/- 7.0 vs. 24.6 +/- 6.9 l/min, p < 0.02), and decreased
      ineffective efforts (3.5 +/- 5.4 vs. 20.3 +/- 12.4 %, p < 0.0001) and inspiratory
      delay (243 +/- 109 vs. 461 +/- 181 ms, p < 0.005). CONCLUSIONS: An optimized set
      up for helmet NIV that limits device compliance and ventilator circuit resistance
      as much as possible is highly effective in improving pressure support delivery
      and patient-ventilator interaction.

PMID- 23011527
TI  - Chest radiographs in 104 French ICUs: current prescription strategies and
      clinical value (the RadioDay study).
AB  - OBJECTIVE: To analyze the current practices of chest radiograph (CXR)
      prescription and their clinical impact. DESIGN: Prospective snapshot
      observational study (on RadioDay) combined with a survey. PATIENTS: Patients who
      were given a CXR on RadioDay. SETTING: One hundred four French intensive care
      units (ICUs). RESULTS: On RadioDay, 854 CXRs (in 804 patients) were ordered. For
      the "CXRs morning round," the prescription policy was declared to be "on-demand"
      (in 63 % of the ICUs), "daily routine only in mechanically ventilated patients
      (MV)" (30 %) or, less frequently, "daily routine in all patients" (7 %). When
      analyzing the two main local policies, as compared with "daily routine only in
      MV" ICUs, in "on-demand" ICUs: (1) fewer CXRs were ordered (0.6 +/- 0.3 vs. 0.9
      +/- 0.2 CXRs/patient, p < 0.001) with no increase in the rate of unscheduled CXRs
      (i.e., CXRs performed outside the morning round), and (2) individual CXRs were
      more often followed by a therapeutic intervention (which would not have occurred
      without the CXR): 34 vs. 25 % of the CXRs (p < 0.05). Last, in case of severe
      respiratory disease (low PaO(2)/FiO(2) ratio), it is noteworthy that the clinical
      value of "on-demand" individual CXRs was still markedly higher than that of
      "daily routine" CXRs. CONCLUSION: Nearly two-thirds of the participating ICUs
      adopted the "on-demand" strategy of prescription, which was associated with a
      lower rate of CXRs with no increase in unscheduled CXRs and was of higher
      clinical value than a "daily routine in MV" strategy. Importantly, the study
      design did not allow assessing if the "on-demand" strategy had missed or delayed
      some diagnoses.

PMID- 23011530
TI  - A comparative assessment of two conservative methods for the diagnosis of
      catheter-related infection in critically ill patients.
AB  - PURPOSE: To assess the utility of two in situ techniques, differential time to
      positivity (DTP) and semiquantitative superficial cultures (SQSC) for diagnosing
      catheter-related bloodstream infection (CR-BSI) in critically ill adults.
      METHODS: This was a prospective cohort study in patients with suspected CR-BSI
      arising from a short-term arterial catheter (AC) or a central venous catheter
      (CVC). On suspicion of CR-BSI, devices were removed. Blood, skin, catheter tip
      and hub cultures were taken. Infection rates were compared against the diagnosis
      of CR-BSI using matched tip and blood cultures. RESULTS: Of 120 episodes of
      clinically suspected CR-BSI in 101 patients examined, 9 (7.5 %) were confirmed as
      CR-BSI. Validity values (95 % CI) for the diagnosis of CR-BSI arising from both
      AC and CVC for DTP were: sensitivity 44 % (15-77 %), specificity 98 % (93-100 %),
      positive predictive value (PPV) 67 % (24-94 %), negative predictive value (NPV)
      96 % (90-98 %), positive likelihood ratio (LR+) 25 (5-117), negative likelihood
      ratio (LR-) 0.6 (0.3-1.0), diagnostic odds ratio (DOR) 44 (7-258), and accuracy
      94 % (92-98 %). Validity values (95 % CI) for SQSC were: sensitivity 78 % (41-96
      %), specificity 60 % (50-69 %), PPV 14 % (6-26 %), NPV 97 % (89-99 %), LR+ 1.9
      (1.0-2.3), LR- 0.4 (0.1-1.3), DOR 5.1 (1.1-19), and accuracy 61 % (51-69 %). DTP
      combined with SQSC improved sensitivity and NPV to 100 % whilst the DOR increased
      to 25.8 (95 % CI 3-454). CONCLUSIONS: CR-BSI can be ruled out by undertaking DTP
      and SQSC concurrently for both ACs and CVCs with 100 % sensitivity and NPV.

PMID- 23011531
TI  - Characteristics and determinants of outcome of hospital-acquired bloodstream
      infections in intensive care units: the EUROBACT International Cohort Study.
AB  - PURPOSE: The recent increase in drug-resistant micro-organisms complicates the
      management of hospital-acquired bloodstream infections (HA-BSIs). We investigated
      the epidemiology of HA-BSI and evaluated the impact of drug resistance on
      outcomes of critically ill patients, controlling for patient characteristics and
      infection management. METHODS: A prospective, multicentre non-representative
      cohort study was conducted in 162 intensive care units (ICUs) in 24 countries.
      RESULTS: We included 1,156 patients [mean +/- standard deviation (SD) age, 59.5
      +/- 17.7 years; 65 % males; mean +/- SD Simplified Acute Physiology Score (SAPS)
      II score, 50 +/- 17] with HA-BSIs, of which 76 % were ICU-acquired. Median time
      to diagnosis was 14 [interquartile range (IQR), 7-26] days after hospital
      admission. Polymicrobial infections accounted for 12 % of cases. Among
      monomicrobial infections, 58.3 % were gram-negative, 32.8 % gram-positive, 7.8 %
      fungal and 1.2 % due to strict anaerobes. Overall, 629 (47.8 %) isolates were
      multidrug-resistant (MDR), including 270 (20.5 %) extensively resistant (XDR),
      and 5 (0.4 %) pan-drug-resistant (PDR). Micro-organism distribution and MDR
      occurrence varied significantly (p < 0.001) by country. The 28-day all-cause
      fatality rate was 36 %. In the multivariable model including micro-organism,
      patient and centre variables, independent predictors of 28-day mortality included
      MDR isolate [odds ratio (OR), 1.49; 95 % confidence interval (95 %CI), 1.07
      2.06], uncontrolled infection source (OR, 5.86; 95 %CI, 2.5-13.9) and timing to
      adequate treatment (before day 6 since blood culture collection versus never, OR,
      0.38; 95 %CI, 0.23-0.63; since day 6 versus never, OR, 0.20; 95 %CI, 0.08-0.47).
      CONCLUSIONS: MDR and XDR bacteria (especially gram-negative) are common in HA
      BSIs in critically ill patients and are associated with increased 28-day
      mortality. Intensified efforts to prevent HA-BSIs and to optimize their
      management through adequate source control and antibiotic therapy are needed to
      improve outcomes.

PMID- 23011532
TI  - Diaphragm electromyographic activity as a predictor of weaning failure.
AB  - PURPOSE: To compare breathing pattern descriptors and diaphragm electromyographic
      activity (EAdi)-derived indices obtained from a neurally adjusted ventilatory
      assist catheter during a spontaneous breathing trial (SBT) in patients
      successfully and unsuccessfully separated from the ventilator and to assess their
      performance as a potential marker to discriminate these two categories of
      patients. METHODS: Fifty-seven ready-to-wean patients were included in a
      prospective observational study. During a 30-min SBT (pressure support 7 cmH(2)O,
      zero end expiratory pressure), tidal volume (V (T)) and respiratory rate (RR)
      were obtained from the flow signal at baseline and at 3, 10, 20 and 30 min during
      the SBT. EAdi-derived indices were simultaneously computed: maximum of the EAdi
      (EAdi(max)), area under the inspiratory curve of EAdi (EAdi(AUC)), the difference
      between EAdi(max) and EAdi(min) (?EAdi), EAdi(max)/V (T), EAdi(AUC)/V (T) and
      ?EAdi/V (T). Patients, successfully (success group; n = 35) and unsuccessfully
      (failure group; n = 22) separated from the ventilator were compared. RESULTS: At
      baseline, the breathing pattern was similar in the two groups, whereas EAdi(max)
      and EAdi(AUC) were significantly lower in the success group (p < 0.05). In the
      failure group, RR and RR/V (T) increased significantly during the trial, V (T)
      decreased, whereas EAdi(max) and EAdi(AUC) did not change. At 3 min, the areas
      under the receiver operating characteristic-curve of RR/V (T) and the EAdi
      derived indices to predict weaning outcome were 0.83 for the rapid shallow
      breathing index (RSBI), 0.84 for EAdi(max)/V (T) , 0.80 for EAdi(AUC)/V (T)
      (0.80) and 0.82 for ?EAdi/V (T). The coefficient of variation for V (T) decreased
      in the failure group while that for EAdi(max) remained unchanged. CONCLUSIONS:
      EAdi-derived indices provide reliable and early predictors of weaning outcome.
      However, the performance of these indices is not better than the RR/V (T).

PMID- 23011533
TI  - Predictive value of bronchoscopy after infant cardiac surgery: a prospective
      study.
AB  - BACKGROUND AND AIMS: Airway evaluation following infant cardiac surgery often
      reveals evidence of tracheobronchial narrowing. We studied the association
      between airway narrowing and extubation failure (EF) in this population. METHODS:
      Prospective cohort study of infants (age <=6 months) from March-September 2009.
      Flexible bronchoscopy (FB) evaluations were obtained using a standardised
      protocol after operative intervention. The primary endpoint was the development
      of extubation failure (EF; defined as the need for invasive mechanical
      ventilation <=48 h after primary extubation) and several secondary endpoints.
      RESULTS: Fifty-three patients were evaluated at a median age of 81 [interquartile
      range (IQR) 13-164] days and weight of 4.2 (IQR 3.2-6.0) kg; 13 (25 %) of the
      patients had single ventricle palliations and two subsequently underwent heart
      transplantation. Significant airway narrowing was noted in 15 of 30 [50 %, 95 %
      confidence interval (CI) 31-69 %] patients who underwent FB; ten of the 53
      patients (19 %, 95 %CI 10-32 %) subsequently developed EF. Narrowed airway
      calibre on bronchoscopy had a sensitivity and specificity of 50 % (95 %CI 28-71
      %) and 50 % (95 %CI 28-71 %), respectively, for EF. The single greatest predictor
      of EF by univariate analysis was the need for preoperative ventilation [odds
      ratio (OR) 6.5, 95 %CI 1.3-33.2, p = 0.03]. Patients with EF had a greater
      likelihood of intensive care readmission (OR 4.8, 95 %CI 1.1-21, p < 0.04) during
      the same hospital admission. CONCLUSIONS: Airway narrowing on FB is noted
      frequently after infant cardiac surgery. Overall assessment and presence of
      narrowing on bronchoscopy had poor sensitivity and specificity for EF in our
      cohort. Expert assessment of tracheobronchial narrowing on FB has poor to
      moderate inter-rater reliability.

PMID- 23011534
TI  - Effects of exogenous hydrogen sulfide on brain metabolism and early neurological
      function in rabbits after cardiac arrest.
AB  - PURPOSE: Some of the neuroprotective effects of hydrogen sulfide (H(2)S) have
      been attributed to systemic hypometabolism and hypothermia. However, systemic
      metabolism may vary more dramatically than brain metabolism after cardiac arrest
      (CA). The authors investigated the effects of inhaled exogenous hydrogen sulfide
      on brain metabolism and neurological function in rabbits after CA and
      resuscitation. METHODS: Anesthetized rabbits were randomized into a sham group, a
      sham/H(2)S group, a CA group, and a CA/H(2)S group. Exogenous 80 ppm H(2)S was
      administered to the sham/H(2)S group and the CA/H(2)S group which suffered 3 min
      of untreated CA by asphyxia and resuscitation. Effects on brain metabolism
      (cerebral extraction of oxygen (CEO(2)), arterio-jugular venous difference of
      glucose [AJVD(glu)] and lactate clearance), S100B, viable neuron counts,
      neurological dysfunction score, and survival rate were evaluated. RESULTS:
      CEO(2), AJVD(glu), and lactate increased significantly after CA. Inhalation of 80
      ppm H(2)S significantly increased CEO(2) (25.04 +/- 7.11 vs. 16.72 +/- 6.12 %)
      and decreased AJVD(glu) (0.77 +/- 0.29 vs. 1.18 +/- 0.38 mmol/L) and lactate
      (5.11 +/- 0.43 vs. 6.01 +/- 0.64 mmol/L) at 30 min after resuscitation when
      compared with the CA group (all P < 0.05). In addition, neurologic deficit
      scores, viable neuron counts, and survival rate were significantly better whereas
      S100B was decreased after H(2)S inhalation. CONCLUSIONS: The present study
      reveals that inhalation of 80 ppm H(2)S reduced neurohistopathological damage and
      improves early neurological function after CA and resuscitation in rabbits. The
      increased CEO(2) and decreased AJVD(glu) and enhanced lactate clearance may be
      involved in the protective effects.

PMID- 23011535
TI  - Estrogen in obesity-associated colon cancer: friend or foe? Protecting
      postmenopausal women but promoting late-stage colon cancer.
AB  - Obesity is associated with the increased incidence of colon cancer. Many cancer
      risk factors have been identified including increased blood levels of insulin,
      leptin, interleukin-6, interleukin-17, tumor necrosis factor-alpha, and decreased
      blood levels of adiponectin. However, the role of blood levels of estrogen in
      obesity-associated colon cancer is controversial. Evidence showed that obesity
      affected men more strongly than women in the carcinogenesis of colon cancer,
      indicating protective effect of estrogen which is increased in obesity. However,
      an epidemiological study has also shown that endogenous estradiol level is an
      independent risk factor for colon cancer, positively associated with colon cancer
      after normalizing insulin, IGF-1. The controversial opinions may be caused by
      different effects of ER-alpha and ER-beta. ER-alpha can increase colon cancer
      cell proliferation and increase cancer incidence. ER-beta has the opposite effect
      to ER-alpha, and it causes apoptosis of colon cancer cells. The normal
      colonocytes mainly express ER-beta. Therefore, increased estrogen in obesity may
      have protective effect via ER-beta in obesity-associated colon cancer. However,
      with the development of colon cancer, ER-alpha is increased and ER-beta is
      decreased. In the late stage of colon cancer, estrogen may promote cancer
      development via ER-alpha. The different effects and expression of ER-alpha and ER
      beta may explain the different results observed in several epidemiological
      studies as well as several animal experiments. Therefore, manipulation of
      estrogen-caused signal pathways to inhibit ER-alpha and stimulate ER-beta may
      have preventive and therapeutic effect for obesity-associated colon cancer.

PMID- 23011536
TI  - Screening practices of Australian men and women categorized as "at or slightly
      above average risk" of colorectal cancer.
AB  - PURPOSE: Australia has one of the highest incidences of colorectal cancer (CRC)
      in the world. In 2006, the federal government introduced a screening program
      consisting of a one-off fecal occult blood test offered to people turning 50, 55,
      or 65 years. We conducted a population-based study to estimate CRC screening
      practices existing outside the current program. METHODS: A total of 1887
      unaffected subjects categorized "at or slightly above average risk" of CRC were
      selected from the Australasian Colorectal Cancer Family Registry. We calculated
      the proportions of participants that reported appropriate, under- and over
      screening according to national guidelines. We performed a logistic regression
      analysis to evaluate associations between over-screening and a set of socio
      demographic factors. RESULTS: Of 532 participants at average risk of CRC,
      eligible for screening, 4 (0.75 %) reported appropriate screening, 479 (90 %)
      reported never having been screened, 18 (3 %) reported some but less than
      appropriate screening, and 31 (6 %) reported over-screening. Of 412 participants
      aged 50 years or over, slightly above average risk of CRC, 1 participant (0.25 %)
      reported appropriate screening, 316 (77 %) reported no screening, and 11 (3 %)
      reported some but less than appropriate screening. Among participants under age
      50 years, 2 % of those at average risk and 10 % of those slightly above average
      risk reported over-screening. Middle-aged people, those with a family history of
      CRC and those with a university degree, were more likely to be over-screened.
      CONCLUSION: Overall, the level of CRC screening participation was low and the
      vast majority of screening tests undertaken were inappropriate in terms of
      timing, modality, or frequency.

PMID- 23011538
TI  - The incidences of malignant gonadal and extragonadal germ cell tumors in males
      and females: a population-based study covering over 40 years in Finland.
AB  - PURPOSE: Germ cell tumors (GCTs) comprise a heterogeneous group of tumors derived
      from primordial germ cells. The incidence of malignant testicular GCTs has
      increased in recent decades, but little is known about possible changes in
      malignant female GCTs. Population-based data covering all malignant GCTs in both
      sexes remain limited. METHODS: All cases of malignant GCTs in 1969-2008 were
      collected from the Finnish Cancer Registry and their age-adjusted annual
      incidences calculated. RESULTS: The overall incidence of malignant GCTs was 2.56
      per 100,000 person-years in males and 0.34 per 100,000 in females. The incidence
      of gonadal GCTs increased from 2.27 to 8.36 per 100,000 in males between 15 and
      44 years of age. Moreover, the incidence of all histological subtypes of gonadal
      GCTs increased in males. In females, the only increase was seen in the incidence
      of ovarian non-dysgerminoma (from 0.07 to 0.29/100,000). The incidence of
      extragonadal GCTs did not change during the study period, being 0.18 and 0.10 per
      100,000 in males and females, respectively. CONCLUSIONS: The incidence of gonadal
      GCTs in males increased significantly during the 40-year study period, whereas in
      females, no such change was observed. There were significant gender differences
      regarding the distribution of histological subtypes and patients' ages. However,
      the incidence of extragonadal GCTs remained low in both sexes. The differences in
      the incidences of gonadal GCTs derived from the same population suggest that the
      risk factors of these malignancies differ between the two sexes.

PMID- 23011537
TI  - A history of allergies is associated with reduced risk of oral squamous cell
      carcinoma.
AB  - PURPOSE: A history of allergies is associated with a decreased risk of several
      types of cancers. Potential mechanisms include enhanced immune surveillance
      against tumor cells early in disease development and/or carcinogenic infectious
      agents. We tested whether allergies are inversely associated with oral squamous
      cell carcinoma (OSCC), accounting for factors that may modify the association,
      such as tumor site, stage, and HPV infection. METHODS: We estimated odds ratios
      (OR) and 95 % confidence intervals (CI) for the association between allergy
      history (including different types of allergies) and OSCC, adjusted for potential
      confounders, among 400 cases and 613 controls. Analyses were also stratified by
      site, stage, and measures of HPV infection. RESULTS: We observed a weak inverse
      association between history of any allergy and OSCC (OR = 0.81, 95 % CI 0.61
      1.08). This association was present only for allergies to airborne allergens
      (dust/pollen/mold) (OR = 0.67; 95 % CI 0.48-0.93). The inverse associations with
      airborne allergies were slightly stronger for oropharyngeal SCC (OR = 0.56; 95 %
      CI 0.35-0.90) than for oral cavity SCC (OR = 0.71; 95 % CI 0.49-1.05) and present
      only for later-stage cancers (OR = 0.42; 95 % CI 0.26-0.66) as opposed to earlier
      stage cancers (OR = 0.98; 95 % CI 0.66-1.46). Inverse associations were not
      particularly present or stronger among HPV-16-seropositive individuals or for HPV
      DNA-positive OSCC. CONCLUSION: There is an inverse association between history of
      allergies to dust, pollen, or mold and OSCC. Whether the inverse association
      involves heightened immune surveillance, increased immune response to HPV or
      other antigen, or other carcinogenic mechanism remains to be determined in more
      definitive studies.

PMID- 23011539
TI  - Polymorphisms in Factor II and Factor V thrombophilia genes among Circassians in
      Jordan.
AB  - Thrombosis is a major cause of morbidity and mortality worldwide. Genetic factors
      are one component of thrombosis. We studied the prevalence of two mutations that
      are known risk factors in the pathogenesis of arterial and venous thrombosis in
      the genetically isolated Circassian population in Jordan. Factor II G20210A and
      Factor V Leiden single nucleotide polymorphisms were analysed by polymerase chain
      reaction and restriction fragment length polymorphism method in 104 random
      unrelated subjects from the Circassian population in Jordan. The prevalence rates
      among the Circassian population in Jordan for Factor II G20210A was 12.2% and for
      Factor V Leiden was 7.7%. We have shown that the population is in Hardy-Weinberg
      equilibrium and that the prevalences of both mutations are within the range of
      other ethnic groups. This is the first study to describe Circassian health
      related genetic characteristics in Jordan. Such population-based studies will
      contribute to understanding the interaction between genetic and environmental
      risk factors. It will remain to be seen whether carriers of Factor II G20210A and
      Factor V Leiden are more likely to develop thrombosis. This issue should be
      studied in the future to determine the need for screening of these mutations
      particularly in thrombophilia patients.

PMID- 23011540
TI  - Recruitment of ethnic minorities into cancer clinical trials: experience from the
      front lines.
AB  - Throughout the world there are problems recruiting ethnic minority patients into
      cancer clinical trials. A major barrier to trial entry may be distrust of
      research and the medical system. This may be compounded by the regulatory
      framework governing research with an emphasis on written consent, closed
      questions and consent documentation, as well as fiscal issues. The Leicester UK
      experience is that trial accrual is better if British South Asian patients are
      approached by a senior doctor rather than someone of perceived lesser
      hierarchical status and a greater partnership between the hospital and General
      Practitioner may increase trial participation of this particular ethnic minority.
      In Los Angeles, USA, trial recruitment was improved by a greater utilisation of
      Hispanic staff and a Spanish language-based education programme. Involvement of
      community leaders is essential. While adhering to national, legal and ethnical
      standards, information sheets and consent, it helps if forms can be tailored
      towards the local ethnic minority population. Written translations are often of
      limited value in the recruitment of patients with no or limited knowledge of
      English. In some cultural settings, tape-recorded verbal consent (following
      approval presentations) may be an acceptable substitute for written consent, and
      appropriate legislative changes should be considered to facilitate this option.
      Approaches should be tailored to specific minority populations, taking
      consideration of their unique characteristics and with input from their community
      leadership.

PMID- 23011541
TI  - The prognostic importance of miR-21 in stage II colon cancer: a population-based
      study.
AB  - BACKGROUND: Despite several years of research and attempts to develop prognostic
      models a considerable fraction of stage II colon cancer patients will experience
      relapse within few years from their operation. The aim of the present study was
      to investigate the prognostic importance of miRNA-21 (miR-21), quantified by in
      situ hybridisation, in a unique, large population-based cohort. PATIENTS AND
      METHODS: The study included 764 patients diagnosed with stage II colon cancer in
      Denmark in the year 2003. One section from a representative paraffin-embedded
      tumour tissue specimen from each patient was processed for analysis of miR-21 and
      quantitatively assessed by image analysis. RESULTS: The miR-21 signal was
      predominantly observed in fibroblast-like cells located in the stromal
      compartment of the tumours. We found that patients expressing high levels of miR
      21 had significantly inferior recurrence-free cancer-specific survival (RF-CSS):
      HR=1.26; 95% CI: 1.15-1.60; P<0.001. In Cox regression analysis, a high level of
      miR-21 retained its prognostic importance and was found to be significantly
      related to poor RF-CSS: HR=1.41; 95% CI: 1.19-1.67; P<0.001. CONCLUSION: The
      present study showed that increasing miR-21 expression levels were significantly
      correlated to decreasing RF-CSS. Further investigations of the clinical
      importance of miR-21 in the selection of high-risk stage II colon cancer patients
      are merited.

PMID- 23011544
TI  - Manuscript 'close shave' margins do not increase rectal cancer recurrence after
      sphincter-saving surgery without neoadjuvant therapy by Lim et al.

PMID- 23011545
TI  - Does preoperative total parenteral nutrition in patients with ulcerative colitis
      produce better outcomes?
AB  - PURPOSE: Malnutrition is a frequent problem in patients with ulcerative colitis
      (UC) leading to increased postoperative complication rates. Preoperative total
      parenteral nutrition (TPN) has been shown to reduce complications in some
      subgroups of patients, but has not been studied in UC. We investigated the impact
      of preoperative TPN on postoperative complication rates in patients undergoing
      surgery for UC. METHODS: This paper is a review of 235 patients who underwent
      surgery for UC; 56 received preoperative TPN and 179 did not. Postoperative
      complication rates were compared. RESULTS: Both had similar rates of anastomotic
      leak (5.4 vs. 2.8 %, p = 0.356), infection (12.5 vs. 20.1 %, p = 0.199),
      ileus/bowel obstruction (21.4 vs. 15.6 %, p = 0.315), cardiac complications (3.6
      vs. 0 %, p = 0.056), wound dehiscence (3.6 vs. 1.7 %, p = 0.595), reoperation
      (10.7 vs. 3.9 %, p = 0.086), and death (1.8 vs. 0 %, p = 0.238). The TPN group
      was more malnourished (albumin 2.49 vs. 3.45, p < 0.001), more often on steroids
      (83.9 vs. 57.5 %, p < 0.001), had more emergent surgery (10.7 vs. 3.4 %, p =
      0.029), more severe colitis (89.3 vs. 65.9 %, p = 0.001), and lower Surgical
      Apgar Score (6.15 vs. 6.57, p = 0.033). After controlling for these with logistic
      regression, the TPN group still had higher complication rates (OR 2.32, p =
      0.04). When line infections were excluded, TPN did not significantly affect
      outcomes (OR 1.5, p = 0.311) CONCLUSION: There were no differences in
      postoperative complications when line infections were excluded. Our data does not
      support routine preoperative TPN in patients with UC. However, it may lead to
      equal surgical outcomes in the sickest and most malnourished patients at the cost
      of line-related morbidity.

PMID- 23011547
TI  - Letter to the editor concerning: Hawkins M, Billingham R, Bastawrous A.
      Hemorrhoid management in patients with radiation proctitis. Int J Colorectal Dis.
      2012 Jun 20. [Epub ahead of print].

PMID- 23011546
TI  - Association study identifying polymorphisms in CD47 and other extracellular
      matrix pathway genes as putative prognostic markers for colorectal cancer.
AB  - PURPOSE: We identified recently the extracellular matrix (ECM) receptor
      interaction pathway as a consistently overrepresented category among gene
      expression profiling studies on colorectal cancer (CRC) prognosis. METHODS:
      Putative regulatory single nucleotide polymorphisms (SNPs) in genes from the ECM
      pathway were genotyped in 613 CRC patients from Northern Germany (PopGen cohort)
      and tested for association with disease progression and survival. RESULTS: The
      eSNP (SNP associated with expression) rs12695175 in CD47 associated with CRC
      specific survival (HR = 2.18, 95 % CI 1.10-4.33, CC versus AA) and with overall
      survival (HR = 1.99, 95 % CI 1.04-3.81, CC versus AA). This association remained
      significant after adjustment for age at diagnosis, tumour stage (T) and lymph
      node status (N). Three polymorphisms in CD47 were associated with distant
      metastasis in a dominant model: rs9879947 and rs3206652 in the 3'-UTR (OR = 1.64,
      95 % CI 1.01-2.64 and OR = 1.88, 95 % CI 1.27-2.80, respectively) and the eSNP
      rs3804639 (OR = 1.73, 95 % CI 1.17-2.57). CONCLUSIONS: The novel associations of
      eSNPs in CD47 with worse survival and distant metastasis should be confirmed by
      additional studies, since increased expression of this gene has recently been
      shown to be an indicator of poor prognosis in cancer patients.

PMID- 23011549
TI  - Sonographic diagnosis of symptomatic ureteral calculi: usefulness of the
      twinkling artifact.
AB  - PURPOSE: Our aim was to analyze the value of ultrasound using the twinkling sign
      in the diagnosis of ureteral stones in patients with renal colic in the emergency
      setting. MATERIALS AND METHODS: Prospective study of 100 patients with suspected
      renal colic who underwent an US examination, including color Doppler mode. We
      analyzed sensitivity, specificity, predictive values, and accuracy. We evaluated
      whether the stone was observed before or after the twinkling artifact, and
      whether the use of the Doppler color increased the examination time. RESULTS: US
      including color Doppler detected 76 of the 84 confirmed lithiasis. The
      sensitivity and specificity were 90 % and 100 %, respectively. The positive
      predictive value was 100 % and the negative 67 %. The accuracy was 92 %. A total
      of 59 calculi (78 %) examined by color Doppler sonography showed the twinkling
      artifact. Seventy percent of the twinkling-positive calculi showed the artifact
      before the stone itself was detected. Considering the location of the stones the
      twinkling sign was seen before the stone in 92 % of lithiasis located in the mid
      lumbar ureter (p = 0.02). The use of the twinkling artifact showed a trend to
      facilitate the detection of smaller calculi (<10 mm) (p = 0.08). The average
      examination time was 5.8 min [+/- 4.3] (without differences between the stones
      detected before or after the twinkling artifact, p = 0.75). CONCLUSION: Doppler
      US examination shows good sensitivity and specificity for the diagnosis of
      symptomatic ureteral stones. The twinkling artifact is useful for the early
      detection of the calculi, especially in the middle tract of the ureter, usually
      the most difficult place in sonographic diagnosis. It also seems helpful for the
      detection of smaller stones. The use of color Doppler does not increase the
      exploration time.

PMID- 23011548
TI  - A pilot study using reduced-volume oral sulfate solution as a preparation for
      colonoscopy among a Japanese population.
AB  - BACKGROUND: This pilot study sought to investigate the performance and safety of
      a reduced-volume oral sulfate solution for use as a bowel-cleansing regimen prior
      to colonoscopy in a Japanese population. METHODS: Subjects followed a prescribed
      split-dose regimen in which the first portion was taken on the evening before
      colonoscopy and the second portion on the morning of the procedure. To determine
      the performance of this regimen, the quality of colon cleansing was assessed in
      each case using a validated four-point scale, and elapsed time to complete the
      preparation was recorded. Side effects and adverse events were investigated by
      blood sampling and questionnaire. RESULTS: The successful preparation rate based
      on the colon-cleansing score was 97 % (30/31). Mean elapsed time to complete the
      preparation on the day of colonoscopy was 71 min. Serum levels of indirect
      bilirubin were significantly increased to abnormal levels following the
      preparation, although these changes were only transient. Preparation-related
      symptoms of nausea and vomiting were presented in only one case. CONCLUSIONS:
      This pilot study showed the oral sulfate solution-based bowel preparation to be
      safe, easy, and quick to use for Japanese patients. A larger study is necessary
      to statistically verify these results.

PMID- 23011550
TI  - Anal carcinoma: FDG PET/CT in staging, response evaluation, and follow-up.
AB  - The role of FDG PET/CT in anal cancer is becoming increasingly important. At the
      time of initial staging, FDG PET/CT can detect the primary site of disease more
      frequently than CT, is sensitive for nodal and metastatic spread and alters
      staging in a significant number of patients. Indeed, the NCCN guidelines for anal
      cancer published in April 2012 recommend FDG PET/CT for therapy planning.
      Metabolic activity of primary anal cancer at presentation is a potential
      biomarker for predicting prognosis, treatment response and survival. More
      intensely FDG-avid primary malignancy is associated with a higher incidence of
      disease spread. Metabolic response following chemoradiotherapy is associated with
      improved survival. The aim of this paper is to provide an up-to-date pictorial
      review of FDG PET/CT in anal cancer at the time of staging and to illustrate its
      utility for determining response to therapy and detecting recurrent disease. 

PMID- 23011551
TI  - CT and MR enterography in evaluating small bowel diseases: when to use which
      modality?
AB  - MR and CT techniques optimized for small bowel imaging are playing an increasing
      role in the evaluation of small bowel disorders. Several studies have shown the
      advantages of these techniques over traditional barium fluoroscopic examinations
      due to improvements in spatial and temporal resolution combined with improved
      bowel distending agents. The preference of MR vs. CT has been geographical and
      based on expertise and public policy. With the increasing awareness of radiation
      exposure, there has been a more global interest in implementing techniques that
      either reduce or eliminate radiation exposure. This is especially important in
      patients with chronic diseases such as inflammatory bowel disease who may require
      multiple studies over a lifetime or in studies that require sequential imaging
      time points such as in assessment of gastrointestinal motility. MRI has many
      properties that make it well suited to imaging of the small bowel: the lack of
      ionizing radiation, the improved tissue contrast that can be obtained by using a
      variety of pulse sequences, and the ability to perform real time functional
      imaging. Moreover, MR modalities allow visualization of the entire bowel, without
      overlapping bowel loops, as well as the detection of both intra- and extraluminal
      abnormalities.The intra- and extraluminal MR findings, combined with contrast
      enhancement and functional information, help to make an accurate diagnosis and
      consequently characterize small bowel diseases.

PMID- 23011552
TI  - Physiological Achilles tendon length and its relation to tibia length.
AB  - OBJECTIVE: The optimal intraoperative Achilles tendon length (ATL) adjustment is
      crucial for the physiological functioning of the musculotendinous unit. To date,
      the resting ATL and its relation to tibia length (TL) have never been defined in
      healthy subjects. We thus performed metric measurements of the ATL and TL.
      DESIGN: Case series. SETTING: Clinical and radiological measurements.
      PARTICIPANTS: Fifty-two subjects placed in a 3-T magnetic resonance imaging with
      the ankle in neutral position. MAIN OUTCOME MEASURES: Unilateral ATL measured
      from the calcaneal insertion to the beginning of the medial gastrocnemius muscle,
      TL measured from the intercondylar eminence to the center of the ankle, and
      qualitative tendon parameters in T2 sequences and human parameters were noted;
      results were correlated with age, gender, body height, weight, body mass index
      (BMI), and side of the AT and TL. RESULTS: The mean ATL was 180.6 +/- 25.0 mm and
      the mean TL was 371.9 +/- 25.4 mm with an ATL:TL ratio of 49 +/- 5%. Achilles
      tendon length correlated significantly with body height (R = 38%, P < 0.0001) and
      with TL (R = 41%, P < 0.0001) but did not correlate with age, BMI, and side of
      the AT. Tibia length correlated with body height (R = 83%, P < 0.0001) and in
      multivariate linear regression, TL was the only independent predictor of ATL
      following the algorithm, ATL (mm) = 0.6 * TL (mm) - 53 (R = 41%). CONCLUSIONS: We
      defined a new way to measure the ATL in a consistent way in healthy subjects and
      showed correlations between ATL, TL and body height and defined an algorithm of
      ATL based on TL. The ATL and the ATL-algorithm might be important in patients
      with impaired tendons such as AT ruptures.

PMID- 23011553
TI  - The role of psychosocial risk factors for injury in elite youth ice hockey.
AB  - OBJECTIVE: To determine the risk of injury associated with athletic identity,
      attitudes toward body checking, competitive state anxiety, and reinjury fear in
      elite youth ice hockey. Also, to determine if there is an elevated risk of
      subsequent injury associated with return to play before medical clearance.
      DESIGN: Cohort study. SETTING: Hockey arenas, Calgary, Alberta. PARTICIPANTS: A
      total of 316 male participants from 18 elite (A, AA, AAA), Bantam (age, 13-14
      years), and Midget (age, 15-17 years) teams. ASSESSMENT OF RISK FACTORS: At
      season commencement and postinjury, participants completed the athletic identity
      measurement scale, competitive state anxiety inventory-2R, body checking
      questionnaire, and fear of reinjury questions. MAIN OUTCOME MEASURES: Hockey
      injury resulting in medical attention, the inability to complete a hockey
      session, and/or missing a subsequent hockey session. RESULTS: Players scoring
      below the 25th percentile in athletic identity were at increased risk of a first
      injury [incidence rate ratios (IRR), 1.53; 95% confidence interval (CI), 1.05
      2.22], but scoring above the 25th percentile was associated with subsequent
      injury (IRR = 2.28; 95% CI, 1.01-6.04). There was no increase in risk associated
      with return to play before clearance (IRR, 1.58; 95% CI, 0.30-5.42). CONCLUSIONS:
      Athletic identity was implicated as an injury risk factor in this population.
      Return to play before medical clearance was not a risk factor in this study, but
      the point estimate warrants additional investigation.

PMID- 23011554
TI  - Illness data from the US Open Tennis Championships From 1994 to 2009.
AB  - OBJECTIVE: To examine the incidence of illness and highlight gender differences
      in tennis players competing in a major professional tennis tournament over a 16
      year period between 1994 and 2009. DESIGN: Descriptive epidemiology study of
      illness trends in professional tennis players. SETTING: Archival data from the US
      Open Tennis Championships. PARTICIPANTS: Participants in the US Open Tennis
      Championships main draw from 1994 to 2009. MAIN OUTCOME MEASURES: Illness data
      collected at the US Open Tennis Championships between 1994 and 2009 were
      classified using guidelines presented in a sport-specific consensus statement.
      Each case was categorized according to the medical system effected and impact on
      play availability during the tournament. Illness rates were determined based on
      the exposure of an athlete to a match event and were calculated as the ratio of
      illness cases per 1000 match exposures (ME). RESULTS: The average number of
      illness cases over the 16-year period analyzed was 58.19 +/- 12.02 per year
      (36.74 per 1000 ME) requiring assistance by the medical staff. Statistical
      analyses showed a significant fluctuation in illness cases related to the
      dermatological (DERM), gastrointestinal, renal/urogenital/gynecological,
      neurological, ophthalmic and otorhinolaryngological (ENT), and infectious medical
      systems (P < 0.05). The ENT and DERM conditions were the most commonly reported
      types of illness for both men and women. CONCLUSIONS: Numerous medical systems
      are susceptible to illness in tennis players. Sport-specific factors may
      influence susceptibility to common illnesses experienced by professional tennis
      players.

PMID- 23011555
TI  - Structure-property relationship of homochiral and achiral supramolecular isomers
      obtained by one-pot synthesis.
AB  - Two supramolecular isomers, {[Co(L)(OBA)].H(2)O}(n) (1),
      {[Co(5)O(2)(L)(2)(OBA)(3)].7DMF}(n) (2), have been synthesized by one-pot
      reactions. Compound 1 has a homochiral architecture with low connectivity, and
      compound 2 is an achiral 3D framework with high 12-connectivity. It is
      unprecedent to get homochiral and achiral supramolecular isomers by one-pot
      synthesis.

PMID- 23011556
TI  - Bicellar systems to modify the phase behaviour of skin stratum corneum lipids.
AB  - Bicellar systems are a fascinating category of versatile lipid assemblies that
      comprise bilayered disk-shaped nanoaggregates formed in water by long and short
      alkyl chain phospholipids. Bicelles bridge the gap between micelles and lipid
      vesicles by combining the attractive properties of both systems. These structures
      have recently been proposed in dermatological, cosmetic and pharmaceutical
      applications. Two new binary bicellar systems composed of cholesterol sulphate
      (SCHOL) and long-chain phospholipids (dimyristoyl-phosphatidylcholine, DMPC, or
      dipalmitoyl-phosphatidylcholine, DPPC) are characterised herein by differential
      scanning calorimetry, fluorescence spectroscopy, X-ray scattering and microscopy.
      Additionally, a comparative study on skin treated with the new SCHOL systems
      (DMPC/SCHOL and DPPC/SCHOL) and classic DHPC systems (DMPC/DHPC and DPPC/DHPC)
      was performed. These studies were conducted to determinate how deeply bicelles
      penetrate into the skin and the extension of their effect on the phase behaviour
      of stratum corneum (SC) lipids using attenuated total reflectance-Fourier
      transform infrared spectroscopy and two-photon excitation fluorescence
      microscopy. Our results show that SCHOL modified the typical discoidal morphology
      and the phase behaviour of the systems, inducing coexistence of two phases,
      liquid-ordered and ripple phases. The effect of the systems on SC lipids depends
      on their composition and is related to the fluidity of the SC lipid alkyl chains.
      Thus, systems with DMPC induced more disorder in SC lipids than systems with
      DPPC, and SCHOL did not modify the lipid arrangement. Perdeuterated systems in
      the infrared spectroscopy technique supported a different distribution in the
      tissue for every system. DMPC systems were primarily at the first layers of the
      SC, whereas DPPC systems were more widely distributed. Systems with SCHOL had
      enhanced distribution and penetration of bicellar systems throughout the SC.

PMID- 23011557
TI  - Graphical user interface simplifies infusion pump programming and enhances the
      ability to detect pump-related faults.
AB  - BACKGROUND: Drug administration errors are frequent and are often associated with
      the misuse of IV infusion pumps. One source of these errors may be the infusion
      pump's user interface. METHODS: We used failure modes-and-effects analyses to
      identify programming errors and to guide the design of a new syringe pump user
      interface. We designed the new user interface to clearly show the pump's
      operating state simultaneously in more than 1 monitoring location. We evaluated
      anesthesia residents in laboratory and simulated environments on programming
      accuracy and error detection between the new user interface and the user
      interface of a commercially available infusion pump. RESULTS: With the new user
      interface, we observed the number of programming errors reduced by 81%, the
      number of keystrokes per task reduced from 9.2 +/- 5.0 to 7.5 +/- 5.5 (mean +/-
      SD), the time required per task reduced from 18.1 +/- 14.1 seconds to 10.9 +/-
      9.5 seconds and significantly less perceived workload. Residents detected 38 of
      70 (54%) of the events with the new user interface and 37 of 70 (53%) with the
      existing user interface, despite no experience with the new user interface and
      extensive experience with the existing interface. CONCLUSIONS: The number of
      programming errors and workload were reduced partly because it took less time and
      fewer keystrokes to program the pump when using the new user interface. Despite
      minimal training, residents quickly identified preexisting infusion pump problems
      with the new user interface. Intuitive and easy-to-program infusion pump
      interfaces may reduce drug administration errors and infusion pump-related
      adverse events.

PMID- 23011558
TI  - Descriptive study of case scheduling and cancellations within 1 week of the day
      of surgery.
AB  - BACKGROUND: We performed a descriptive study of operating room (OR) case
      scheduling within 1 week of the day of surgery. METHODS: The data used were from
      the case scheduling and transaction audit tables of a hospital's anesthesia and
      OR information management systems. Each change to a scheduled case in the OR
      information system was captured in an audit table, including the date and time
      when the change was made. The timestamps allowed reconstruction of the elective
      OR schedule for each date of surgery at preceding dates (e.g., 2 workdays ahead).
      The sample size was n = 17 consecutive 4-week periods. The allocated OR time, for
      each combination of service and day of the week, was the number of hours that
      minimized the inefficiency of use of OR time, a weighted combination of the hours
      of underutilized OR time and the more expensive hours of overutilized OR time.
      Data are reported as mean +/-SE. RESULTS: (1) The percentage of OR date
      combinations with at least 1 add-on case was 24.1% +/- 0.3%. The most recent
      addition of a case to an OR occurred 1 working day before surgery for 22.3% +/-
      0.4% of OR date combinations. At least half (51.5% +/- 0.5%) of ORs had its last
      case scheduled or changed within 2 working days of surgery. In addition, when
      allocated OR time was filled and the service scheduled additional case(s), the
      median time ahead when each such case was scheduled was 2.2 +/- 0.2 workdays.
      Thus, managers can productively focus on the day of surgery starting 2 working
      days before surgery. (2) Once allocated time was full, the ratio of the net
      additional cases scheduled to the total number performed was 1.2% +/- 0.6%.
      However, 11.1% +/- 1.7% of the total were additional cases. Thus, schedulers
      should rely on the allocated time to be predictive of the actual (net) workload
      that will occur in the future, on the day of surgery. (3) For service and day
      combinations for which 2 working days ahead the scheduled hours exceeded the
      allocated hours, there was no significant net increase in minutes of cases
      scheduled (P = 0.79), unlike when the scheduled hours were less than allocated (P
      < 0.0001). Thus, additional hours of cases scheduled within the same number of
      workdays are heterogeneous both within and among services based on the prior
      hours of cases scheduled. CONCLUSIONS: Planning anesthesia assignments, ORs to
      target, etc., can be done productively starting 2 working days ahead of surgery.
      There are so many changes to the OR schedule those last 2 workdays that
      anesthesia groups should be engaged with the scheduling office during that
      period. The primary predictor of additional net hours of cases to be scheduled is
      the difference between the allocated (i.e., forecasted) OR time and the hours
      scheduled so far.

PMID- 23011559
TI  - Core review: physician-performed ultrasound: the time has come for routine use in
      acute care medicine.
AB  - The use of ultrasound in the acute care specialties of anesthesiology, intensive
      care, emergency medicine, and surgery has evolved from discrete, office-based
      echocardiographic examinations to the real-time or point-of-care clinical
      assessment and interventions. "Goal-focused" transthoracic echocardiography is a
      limited scope (as compared with comprehensive examination) echocardiographic
      examination, performed by the treating clinician in acute care medical practice,
      and is aimed at addressing specific clinical concerns. In the future, the
      practice of surface ultrasound will be integrated into the everyday clinical
      practice as ultrasound-assisted examination and ultrasound-guided procedures.
      This evolution should start at the medical student level and be reinforced
      throughout specialist training. The key to making ultrasound available to every
      physician is through education programs designed to facilitate uptake, rather
      than to prevent access to this technology and education by specialist craft
      groups. There is evidence that diagnosis is improved with ultrasound examination,
      yet data showing change in management and improvement in patient outcome are few
      and an important area for future research.

PMID- 23011560
TI  - A single preoperative dose of gabapentin does not improve postcesarean delivery
      pain management: a randomized, double-blind, placebo-controlled dose-finding
      trial.
AB  - BACKGROUND: A single preoperative dose of 600 mg gabapentin, combined with
      multimodal analgesia, has previously been shown to reduce postcesarean pain and
      improve maternal satisfaction but was associated with increased maternal
      sedation. We hypothesized that a lower dose of gabapentin may be effective with
      less sedation. METHODS: We conducted a doubleblind, randomized, placebo
      controlled study. Women undergoing elective cesarean delivery were randomized
      into 3 groups to receive 300 or 600 mg oral gabapentin, or placebo, 1 hour before
      surgery. Temporal summation (TS) testing was performed at the time of study drug
      administration, and a visual analog scale (0 to 100 mm) difference >=10 mm
      between the 1st and 10th stimuli was considered TS+. Spinal anesthesia and
      postoperative analgesia were instituted, including intrathecal fentanyl and
      morphine, oral diclofenac and acetaminophen, and systemic morphine as required.
      Pain assessments at rest and on movement (visual analog scale 0 to 100 mm) were
      conducted at 6, 12, 24, and 48 hours after surgical incision. The primary outcome
      was pain on movement at 24 hours. Secondary outcomes included satisfaction with
      analgesia, supplemental opioid consumption, lactation difficulties, neonatal
      outcomes, maternal sedation, and other adverse effects. Three months after
      delivery, patients were contacted for assessment of chronic pain. RESULTS: One
      hundred thirty-two women were randomized and 6 were excluded. The difference in
      mean pain scores at 24 hours (95% confidence intervals [CI]) were as follows: 600
      mg versus 300 mg mean difference: 5 mm (95% adjusted CI, -7 to 17); 600 mg versus
      placebo: 3 mm (-9 to 15); 300 mg versus placebo: -2 mm [-14 to 10]; overall P
      value = 0.61. There was no apparent benefit of gabapentin in TS+ women, although
      overall pain scores were significantly higher in these women irrespective of the
      study group. CONCLUSION: Given the wide confidence intervals of the differences
      in mean pain scores, the current study did not allow us to determine whether a
      single preoperative dose of gabapentin (300 mg and 600 mg) improved postcesarean
      analgesia compared to placebo in the context of a multimodal analgesic regimen. A
      larger study is required.

PMID- 23011561
TI  - The effect of perioperative intravenous lidocaine and ketamine on recovery after
      abdominal hysterectomy.
AB  - BACKGROUND: Perioperative ketamine infusion reduces postoperative pain;
      perioperative lidocaine infusion reduces postoperative narcotic consumption,
      speeds recovery of intestinal function, improves postoperative fatigue, and
      shortens hospital stay. However, it is unknown whether perioperative IV lidocaine
      and/or ketamine enhances acute functional recovery. We therefore tested the
      primary hypothesis that perioperative IV lidocaine and/or ketamine in patients
      undergoing open abdominal hysterectomy improves rehabilitation as measured by a 6
      minute walk distance (6-MWD) on the second postoperative morning. METHODS: Women
      having open hysterectomy were anesthetized with sevoflurane, followed by patient
      controlled morphine. Patients were factorially randomized to one of the following
      groups: (1) lidocaine and placebo, (2) placebo and ketamine, (3) placebo and
      placebo, or (4) lidocaine and ketamine. Lidocaine was given as a bolus (1.5
      mg/kg), followed by lidocaine infusion of 2 mg/kg/h for the first 2 hours, and
      then 1.2 mg/kg/h for 24 postoperative hours. Ketamine was given as a bolus (0.35
      mg/kg), followed by ketamine infusion of 0.2 mg/kg/h for the first 2 hours, and
      then 0.12 mg/kg/h for 24 postoperative hours. The primary double-blind outcome
      was 6-MWD on the second postoperative morning; secondary outcomes included pain
      scores, opioid consumption, postoperative nausea and vomiting, and fatigue score.
      RESULTS: The study was stopped after a planned interim analysis of 64 patients
      showed that lidocaine crossed the preplanned futility boundary, with mean +/- SD
      of 202 +/- 66 m versus 202 +/- 73 m for lidocaine versus placebo, respectively,
      and mean difference (interim adjusted 97.5% confidence interval) of 0.93 m (-52,
      54) (P = 0.96); the ketamine effect also crossed the futility boundary, with mean
      +/- SD of 193 +/- 77 m versus 210 +/- 61 m for ketamine versus placebo,
      respectively, and mean difference (interim adjusted 97.5% confidence interval) of
      -11 m (-65, 44) (P = 0.54). No interaction between the 2 intervention effects was
      observed (P = 0.96). Neither intervention significantly influenced any of the
      secondary outcomes. CONCLUSION: Our results do not support use of lidocaine or
      ketamine for improving 6-MWD on the second postoperative day after open
      hysterectomy.

PMID- 23011562
TI  - Phenylephrine infusion versus bolus regimens during cesarean delivery under
      spinal anesthesia: a double-blind randomized clinical trial to assess hemodynamic
      changes.
AB  - INTRODUCTION: Phenylephrine is used to prevent and treat hypotension during
      spinal anesthesia for cesarean delivery. The optimal administration regimen is
      undetermined. We used a Non-invasive cardiac output monitor to test the
      hypothesis that a fixed-rate phenylephrine infusion regimen would cause a smaller
      reduction in maternal cardiac output, and result in less maternal hypotension, as
      compared to a phenylephrine bolus regimen. METHODS: This was a double-blind,
      randomized clinical trial of women undergoing elective cesarean delivery under
      spinal anesthesia. Patients were randomized to an intermittent bolus (120 MUg) or
      a fixed-rate infusion (120 MUg/min) regimen of phenylephrine. Any decrease in
      systolic blood pressure from baseline was treated. The primary outcome was the
      maximum change in cardiac output in the predelivery period, assessed using
      bioreactance technology. Secondary outcomes included the maximum change in heart
      rate, incidence of hypo- and hypertension, nausea/vomiting and bradycardia, total
      dose of phenylephrine, umbilical blood gases, and Apgar scores. The hemodynamic
      profiles over time in each treatment arm were compared. RESULTS: Sixty patients
      were studied. There was no significant difference in the maximum change in
      cardiac output between the 2 treatment arms: mean (SD) maximum change in cardiac
      output in the bolus group was 1.87 (1.68) L/min versus 1.9 (1.46) L/min in the
      infusion group (P = 0.94) (95% confidence intervals of difference in means: -0.84
      to 0.78 L/min). The infusion group received significantly more phenylephrine
      (1740 (613) versus 964 (454) MUg) (P < 0.001). In the initial 6 min after
      intrathecal injection, there was a significant decrease in blood pressure in the
      infusion group compared to the bolus group (P = 0.007). There was no significant
      difference in the other secondary outcomes. CONCLUSION: There were no clinical
      benefits to administering phenylephrine as an infusion versus a bolus regimen.
      The bolus regimen maintained maternal arterial blood pressure closer to baseline
      in the initial minutes after spinal injection but this had no clinical benefits.
      The infusion regimen required a higher total dose of phenylephrine to maintain
      maternal arterial blood pressure at baseline during the predelivery period.

PMID- 23011563
TI  - Cartoon distraction alleviates anxiety in children during induction of
      anesthesia.
AB  - BACKGROUND: We performed this study to determine the beneficial effects of
      viewing an animated cartoon and playing with a favorite toy on preoperative
      anxiety in children aged 3 to 7 years in the operating room before anesthesia
      induction. METHODS: One hundred thirty children aged 3 to 7 years with ASA
      physical status I or II were enrolled. Subjects were randomly assigned to 1 of 3
      groups: group 1 (control), group 2 (toy), and group 3 (animated cartoon). The
      children in group 2 were asked to bring their favorite toy and were allowed to
      play with it until anesthesia induction. The children in group 3 watched their
      selected animated cartoon until anesthesia induction. Children's preoperative
      anxiety was determined by the modified Yale Preoperative Anxiety Scale (mYPAS)
      and parent-recorded anxiety Visual Analog Scale (VAS) the night before surgery,
      in the preanesthetic holding room, and just before anesthesia induction. RESULTS:
      In the preanesthetic holding room, the group 2 mYPAS and parent-recorded anxiety
      VAS scores were significantly lower than those of groups 1 and 3 (mYPAS: P =
      0.007; parent-recorded anxiety VAS: P = 0.02). In the operating room, the
      children in group 3 had the lowest mYPAS and parent-recorded anxiety VAS scores
      among the 3 groups (mYPAS: P < 0.001; parent-recorded anxiety VAS: P < 0.001). In
      group 3, the mYPAS and parent-recorded anxiety VAS scores of only 3 and 5
      children were increased in the operating room compared with their scores in the
      preanesthetic holding room, whereas the anxiety scores of 32 and 34 children in
      group 1 and 25 and 32 children in group 2 had increased (P < 0.001). The number
      of children whose scores indicated no anxiety (mYPAS score <30) in the operating
      room was 3 (7%), 9 (23%), and 18 (43%) in groups 1, 2, and 3, respectively (P <
      0.001). CONCLUSIONS: Allowing the viewing of animated cartoons by pediatric
      surgical patients is a very effective method to alleviate preoperative anxiety.
      Our study suggests that this intervention is an inexpensive, easy to administer,
      and comprehensive method for anxiety reduction in the pediatric surgical
      population.

PMID- 23011564
TI  - Ginkgo biloba extract attenuates hyperalgesia in a rat model of vincristine
      induced peripheral neuropathy.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common, dose-limiting
      side effect of cancer chemotherapeutic drugs. Hyperalgesia is a common component
      of neuropathic pain. Ginkgo biloba extract (GBE) is an oriental herbal medicine
      that has various pharmacological actions. In this study, we evaluated the effects
      of oral GBE on hyperalgesia in a rat model of vincristine-induced neuropathy.
      METHODS: Male Sprague-Dawley rats (200-250 g) were injected intraperitoneally
      with vincristine or saline (0.1 mg/kg/d) using a 5-day-on, 2-day-off schedule
      over 12 days. All the behavioral tests for mechanical, cold, and heat
      hyperalgesia were conducted before the daily injection during the course of
      vincristine treatment. Rats that developed hyperalgesia 14 days after vincristine
      injection were randomly assigned into 4 groups. Distilled water and GBE (50, 100,
      and 150 mg/kg) were administered, respectively, to the individual groups. We
      examined the hyperalgesia at preadministration and at 15, 30, 60, 90, 120, 150,
      and 180 minutes after oral drug administration. RESULTS: Saline injection did not
      have any significant effect on mechanical, cold, and heat hyperalgesia.
      Vincristine injection produced mechanical and cold hyperalgesia. For the GBE
      groups, the paw withdrawal threshold to mechanical stimuli was significantly
      increased and withdrawal frequency to cold stimuli was significantly reduced
      versus the control group dose-dependently (P < 0.05). CONCLUSIONS: This study
      demonstrates that oral administration of GBE is associated with a dose-dependent
      antihyperalgesic effect on mechanical and cold stimuli in a rat model of
      vincristine-induced neuropathy.

PMID- 23011565
TI  - Speaking up is related to better team performance in simulated anesthesia
      inductions: an observational study.
AB  - BACKGROUND: Our goal in this study was to test the relationship between speaking
      up--i.e., questioning, correcting, or clarifying a current procedure--and
      technical team performance in anesthesia. Hypothesis 1: team members' higher
      levels of speaking up are related to higher levels of technical team performance.
      Hypothesis 2: team members will react to speaking up by either clarifying their
      procedure or initiating a procedural change. Hypothesis 3: higher levels of
      speaking up during an earlier phase of teamwork will be related to higher levels
      of speaking up during a later phase. METHODS: This prospective observational
      study involved 2-person ad hoc anesthesia teams performing simulated inductions
      of general anesthesia with minor nonroutine events (e.g., bradycardia) in a large
      teaching hospital. Subjects were registered anesthesia nurses and residents. Each
      team consisted of 1 nurse and 1 resident. Synchronized video and vital parameter
      recordings were obtained. Two trained observers blinded to the hypotheses coded
      speaking up and further team communication and coordination behavior on the basis
      of 12 distinct categories. All teamwork measures were quantified as percentage of
      total time spent on the respective teamwork category. Two experienced staff
      anesthesiologists blinded to the hypotheses evaluated technical team performance
      using a Delphi-validated rating checklist. Hypotheses 1 and 3 were tested using
      linear regression with residents' and nurses' levels of speaking up as 2 separate
      predictor variables. Hypothesis 2 was analyzed using lag sequential analysis,
      resulting in Z values representing the extent to which the observed value for a
      conditional transition significantly differs from its unconditional value.
      RESULTS: Thirty-one nurses and 31 residents participated. Technical team
      performance could be predicted by the level of speaking up from nurses (R(2) =
      0.18, P = 0.017) but not from residents (R(2) = 0.19, P = 0.053); this result
      supports Hypothesis 1 for nurses. Supporting Hypothesis 2, residents reacted to
      speaking up with clarifying the procedure by providing information (Z = 18.08, P
      < 0.001), initiating procedural change by giving instructions (Z = 4.74, P <
      0.001) and team member monitoring (Z = 3, P = 0.0013). Likewise, nurses reacted
      with clarifying the procedure by providing or evaluating information (Z = 16.09,
      P < 0.001; Z = 3.72, P < 0.001) and initiating procedural change by providing
      assistance (Z = 0.57, P < 0.001). Indicating a trend for Hypothesis 3, nurses'
      level of speaking up before intubation predicted their level of speaking up
      during intubation (R(2) = 0.15, P = 0.034), although this did not reach the
      Bonferroni-corrected significance level of P = 0.025. No respective relationship
      was found for residents (R(2) = 0.15, P = 0.096). CONCLUSIONS: This study
      provides empirical evidence and shows mechanisms for the positive relationship
      between speaking-up behavior and technical team performance.

PMID- 23011567
TI  - Chemical and genetic exploration of jasmonate biosynthesis and signaling paths.
AB  - Jasmonates are lipid-derived compounds that act as signals in plant stress
      responses and developmental processes. Enzymes participating in biosynthesis of
      jasmonic acid (JA) and components of JA signaling have been extensively
      characterized by biochemical and molecular-genetic tools. Mutants have helped to
      define the pathway for synthesis of jasmonoyl-L-isoleucine (JA-Ile), the
      bioactive form of JA, and to identify the F-box protein COI1 as central
      regulatory unit. Details on the molecular mechanism of JA signaling were recently
      unraveled by the discovery of JAZ proteins that together with the adaptor protein
      NINJA and the general co-repressor TOPLESS form a transcriptional repressor
      complex. The current model of JA perception and signaling implies the SCF(COI1)
      complex operating as E3 ubiquitin ligase that upon binding of JA-Ile targets JAZ
      proteins for degradation by the 26S proteasome pathway, thereby allowing MYC2 and
      other transcription factors to activate gene expression. Chemical strategies, as
      integral part of jasmonate research, have helped the establishment of structure
      activity relationships and the discovery of (+)-7-iso-JA-L-Ile as the major
      bioactive form of the hormone. The transient nature of its accumulation
      highlights the need to understand catabolism and inactivation of JA-Ile and
      recent studies indicate that oxidation of JA-Ile by cytochrome P450 monooxygenase
      is the major mechanism for turning JA signaling off. Plants contain numerous JA
      metabolites, which may have pronounced and differential bioactivity. A major
      challenge in the field of plant lipid signaling is to identify the cognate
      receptors and modes of action of these bioactive jasmonates/oxylipins.

PMID- 23011568
TI  - Inhibition of chlorophyll biosynthesis at the protochlorophyllide reduction step
      results in the parallel depletion of Photosystem I and Photosystem II in the
      cyanobacterium Synechocystis PCC 6803.
AB  - In most oxygenic phototrophs, including cyanobacteria, two independent enzymes
      catalyze the reduction of protochlorophyllide to chlorophyllide, which is the
      penultimate step in chlorophyll (Chl) biosynthesis. One is light-dependent
      NADPH:protochlorophyllide oxidoreductase (LPOR) and the second type is dark
      operative protochlorophyllide oxidoreductase (DPOR). To clarify the roles of both
      enzymes, we assessed synthesis and accumulation of Chl-binding proteins in
      mutants of cyanobacterium Synechocystis PCC 6803 that either completely lack LPOR
      or possess low levels of the active enzyme due to its ectopic regulatable
      expression. The LPOR-less mutant grew photoautotrophically in moderate light and
      contained a maximum of 20 % of the wild-type (WT) Chl level. Both Photosystem II
      (PSII) and Photosystem I (PSI) were reduced to the same degree. Accumulation of
      PSII was mostly limited by the synthesis of antennae CP43 and especially CP47 as
      indicated by the accumulation of reaction center assembly complexes. The
      phenotype of the LPOR-less mutant was comparable to the strain lacking DPOR that
      also contained <25 % of the wild-type level of PSII and PSI when cultivated under
      light-activated heterotrophic growth conditions. However, in the latter case, we
      detected no reaction center assembly complexes, indicating that synthesis was
      almost completely inhibited for all Chl-proteins, including the D1 and D2
      proteins.

PMID- 23011569
TI  - Enzymatic cell wall degradation of Chlorella vulgaris and other microalgae for
      biofuels production.
AB  - Cell walls of microalgae consist of a polysaccharide and glycoprotein matrix
      providing the cells with a formidable defense against its environment. We
      characterized enzymes that can digest the cell wall and weaken this defense for
      the purpose of protoplasting or lipid extraction. A growth inhibition screen
      demonstrated that chitinase, lysozyme, pectinase, sulfatase, beta-glucuronidase,
      and laminarinase had the broadest effect across the various Chlorella strains
      tested and also inhibited Nannochloropsis and Nannochloris strains. Chlorella is
      typically most sensitive to chitinases and lysozymes, both enzymes that degrade
      polymers containing N-acetylglucosamine. Using a fluorescent DNA stain, we
      developed rapid methodology to quantify changes in permeability in response to
      enzyme digestion and found that treatment with lysozyme in conjunction with other
      enzymes has a drastic effect on cell permeability. Transmission electron
      microscopy of enzymatically treated Chlorella vulgaris indicates that lysozyme
      degrades the outer surface of the cell wall and removes hair-like fibers
      protruding from the surface, which differs from the activity of chitinase. This
      action on the outer surface of the cell causes visible protuberances on the cell
      surface and presumably leads to the increased settling rate when cells are
      treated with lysozyme. We demonstrate radical ultrastructural changes to the cell
      wall in response to treatment with various enzyme combinations which, in some
      cases, causes a greater than twofold increase in the thickness of the cell wall.
      The enzymes characterized in this study should prove useful in the engineering
      and extraction of oils from microalgae.

PMID- 23011571
TI  - Genetics, evolution, and the zoonotic capacity of European Swine influenza
      viruses.
AB  - The European swine influenza virus lineage differs genetically from the classical
      swine influenza viruses and the triple reassortants found in North America and
      Asia. The avian-like swine H1N1 viruses emerged in 1979 after an avian-to-swine
      transmission and spread to all major European pig-producing countries.
      Reassortment of these viruses with seasonal H3N2 viruses led to human-like swine
      H3N2 viruses which appeared in 1984. Finally, human-like swine H1N2 viruses
      emerged in 1994. These are triple reassortants comprising genes of avian-like
      H1N1, seasonal H1N1, and seasonal H3N2 viruses. All three subtypes established
      persistent infection chains and became prevalent in the European pig population.
      They successively replaced the circulating classical swine H1N1 viruses of that
      time and gave rise to a number of reassortant viruses including the pandemic
      (H1N1) 2009 virus. All three European lineages have the capacity to infect humans
      but zoonotic infections are benign.

PMID- 23011570
TI  - Involvement of nitrite in the nitrate-mediated modulation of fermentative
      metabolism and nitric oxide production of soybean roots during hypoxia.
AB  - It is widely accepted that nitrate but not ammonium improves tolerance of plants
      to hypoxic stress, although the mechanisms related to this beneficial effect are
      not well understood. Recently, nitrite derived from nitrate reduction has emerged
      as the major substrate for the synthesis of nitric oxide (NO), an important
      signaling molecule in plants. Here, we analyzed the effect of different nitrogen
      sources (nitrate, nitrite and ammonium) on the metabolic response and NO
      production of soybean roots under hypoxia. Organic acid analysis showed that root
      segments isolated from nitrate-cultivated plants presented a lower accumulation
      of lactate and succinate in response to oxygen deficiency in relation to those
      from ammonium-cultivated plants. The more pronounced lactate accumulation by root
      segments of ammonium-grown plants was followed by a higher ethanol release in the
      medium, evidencing a more intense fermentation under oxygen deficiency than those
      from nitrate-grown plants. As expected, root segments from nitrate-cultivated
      plants produced higher amounts of nitrite and NO during hypoxia compared to
      ammonium cultivation. Exogenous nitrite supplied during hypoxia reduced both
      ethanol and lactate production and stimulated cyanide-sensitive NO emission by
      root segments from ammonium-cultivated plants, independent of nitrate. On the
      other hand, treatments with a NO donor or a NO scavenger did not affect the
      intensity of fermentation of soybean roots. Overall, these results indicate that
      nitrite participates in the nitrate-mediated modulation of the fermentative
      metabolism of soybean roots during oxygen deficiency. The involvement of
      mitochondrial reduction of nitrite to NO in this mechanism is discussed.

PMID- 23011572
TI  - The Medical Expenditure Panel Survey (MEPS) experiences with cancer survivorship
      supplement.
AB  - INTRODUCTION: The prevalence of cancer survivorship in the USA is expected to
      increase in the future because the US population is increasing in size and is
      aging and because survival following diagnosis is improving for many types of
      cancer. Medical care costs associated with cancer are also projected to increase
      dramatically. However, currently available data for estimating medical care costs
      and other important aspects of the burden of cancer, including time spent
      receiving medical care, productivity loss due to morbidity for patients and their
      families, and financial hardship, are limited, particularly in the population
      under the age of 65. METHODS: We describe selected publicly available data
      sources for estimating the burden of cancer in the USA and a new collaborative
      effort to improve the quality of these data: the nationally representative
      Medical Expenditure Panel Survey (MEPS) Experiences with Cancer Survivorship
      Supplement. CONCLUSIONS: Data from this effort can be used to address key gaps in
      cancer survivorship research related to medical care costs, employment patterns,
      financial hardship, and other aspects of the burden of illness for cancer
      survivors and their families. IMPLICATIONS FOR CANCER SURVIVORS: Research using
      the MEPS Experiences with Cancer Survivorship Supplement can inform efforts by
      health care policy makers, healthcare systems, providers, and employers to
      improve the cancer survivorship experience in the USA.

PMID- 23011573
TI  - Prevention of relapse with maintenance electroconvulsive therapy in elderly
      patients with major depressive episode.
AB  - OBJECTIVES: To evaluate the effectiveness and safety of maintenance
      electroconvulsive therapy (mECT) in elderly patients with treatment-resistant
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major
      depressive episode. METHODS: Seven elderly patients with treatment-resistant
      major depressive episode were treated with a complete ECT cycle. Thereafter, they
      received one monthly ECT session as maintenance for 1 year. Response to treatment
      was defined as at least a 50% drop from baseline on the Hamilton Depression
      Rating Scale (HamD) and remission as not meeting criteria for major depression, a
      HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness
      score of 1. We compared their response with the response of 7 elderly patients
      with treatment-resistant major depression who were treated with a full cycle of
      ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number
      of relapses or recurrences of major depressive episodes after remission was
      achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher,
      or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      Text Revision major depressive episode criteria were met, or when Clinical Global
      Impressions-Severity of Illness score was 3 or higher and increased by at least 2
      points from response/remission. RESULTS: The mECT group (4 women and 3 men; mean
      age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and
      hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group
      (similar for age and sex composition) during the 12-month follow-up period. All
      patients with mECT improved during treatment and did not relapse. CONCLUSIONS:
      Maintenance ECT protected elderly patients from recurrent depressive episodes
      from relapsing/recurring more than standard ECT.

PMID- 23011574
TI  - Influence of the spinning rate in the HR-MAS pattern of mobile lipids in C6
      glioma cells and in artificial oil bodies.
AB  - OBJECT: To evaluate how spinning rate affects mobile lipid (ML) resonances
      visibility in HR-MAS spectra of C6 glioma cells and artificial oil bodies (AOB),
      as models of cytosolic lipid droplets. MATERIALS AND METHODS: Using C6 cells and
      AOB of two different sizes, 780 +/- 580 and 240 +/- 293 nm, as models, we
      acquired HR-MAS pulse and acquire spectra at different spinning rates between 500
      and 15,000 Hz, all at 37  degrees C. RESULTS: Sample spinning at 15,000 Hz
      increased by 2.3 and 4.6-fold with respect to 500 Hz spinning the area of
      resonances corresponding to ML at 0.88 and 1.28 ppm, respectively, for log phase
      C6 cells. Furthermore, postconfluent C6 cells displayed an increase of 2.5-fold
      at 0.88 ppm and 4.2-fold at 1.28 ppm. These changes were reversible upon low
      speed spinning. AOBs did show much lower ML area increases (1.4-1.5-fold) upon
      high-speed HR-MAS. CONCLUSION: ML can be reversibly mobilized in C6 glioma cells
      by high-speed HR-MAS, partially unveiling the NMR "invisible" ML pool. A small
      part of the ML pool also shows reduced visibility in freely tumbling AOBs.

PMID- 23011577
TI  - Ionothermal synthesis of sulfur-doped porous carbons hybridized with graphene as
      superior anode materials for lithium-ion batteries.
AB  - Sulfur-doped porous carbons hybridized with graphene (SPC@G) have been
      synthesized via a simple ionothermal method. The obtained SPC@G nanocomposite
      exhibits both high capacity and excellent rate performance, making it a promising
      anode material for lithium-ion batteries.

PMID- 23011575
TI  - A simple score for rapid risk assessment of non-high-risk pulmonary embolism.
AB  - OBJECTIVE: We tested whether bedside testing for H-FABP is, alone or integrated
      in combination models, useful for rapid risk stratification of non-high-risk PE.
      METHODS: We prospectively studied 136 normotensive patients with confirmed PE. H
      FABP was determined using a qualitative bedside-test showing a positive result
      for plasma concentration >7 ng/ml. RESULTS: Overall, 11 patients (8.1 %) had an
      adverse 30-day outcome. Of 58 patients (42.6 %) with a positive H-FABP bedside
      test, 9 (15.5 %) had an unfavourable course compared to 2 of 78 patients (2.6 %)
      with a negative test result (p = 0.009). Logistic regression analysis indicated a
      sevenfold increased risk for an adverse outcome (95 % CI, 1.45-33.67; p = 0.016)
      for patients with a positive H-FABP bedside-test. Additive prognostic information
      were obtained by a novel score including the H-FABP bedside-test (1.5 points),
      tachycardia (2 points), and syncope (1.5 points) (OR 11.57 [2.38-56.24]; p =
      0.002 for >=3 points). Increasing points were associated with a continuous
      exponential increase in the rate of an adverse 30-day outcome (0 % for patients
      with 0 points and 44.4 % for >=5 points). Notably, this simple score provided
      similar prognostic value as the combination of the H-FABP bedside-test with
      echocardiographic signs of right ventricular dysfunction (OR 12.73 [2.51-64.43];
      p = 0.002). CONCLUSIONS: Bedside testing for H-FABP appears a useful tool for
      immediate risk stratification of non-high-risk patients with acute PE, who may be
      at increased risk of an adverse outcome, in particular if integrated in a novel
      score without the need of echocardiographic examination.

PMID- 23011576
TI  - Socio-ecological influences on health-care access and navigation among persons of
      Mexican descent living on the U.S./Mexico border.
AB  - The study reported here examines factors influencing decision-making concerning
      health care access and navigation among persons of Mexican origin living along
      the U.S./Mexico border. Specifically, the study examined how persons with limited
      financial resources accessed these two systems. Seven focus groups were held with
      52 low income Mexican American people aged 18-65 years. Transcripts were analyzed
      to identify themes in Atlasti 5.0 software and the theory used included a socio
      ecological framework and complemented by constructed from the Social Cognitive
      Theory. We found that in addition to a lack of insurance and financial resources
      to pay for health care; fear, embarrassment and denial associated with a
      diagnosis of illness; poor medical personnel interactions, and desire for quality
      but streamlined health care also influenced decision making. This theory-based
      study raises important issues if health care is to improve the health and welfare
      of disadvantaged populations and points to the need for greater focus on medical
      homes and prevention and early intervention approaches.

PMID- 23011578
TI  - Iron transport and storage in the coccolithophore: Emiliania huxleyi.
AB  - Iron is an essential element for all living organisms due to its ubiquitous role
      in redox and other enzymes, especially in the context of respiration and
      photosynthesis. The iron uptake and storage systems of terrestrial/higher plants
      are now reasonably well understood with two basic strategies for iron uptake
      being distinguished: strategy I plants use a mechanism involving soil
      acidification and induction of Fe(III)-chelate reductase (ferrireductase) and
      Fe(II) transporter proteins while strategy II plants have evolved sophisticated
      systems based on high-affinity, iron specific, binding compounds called
      phytosiderophores. In contrast, there is little knowledge about the corresponding
      systems in marine plant-like lineages. Herein we report a study of the iron
      uptake and storage mechanisms in the coccolithophore Emiliania huxleyi. Short
      term radio-iron uptake studies indicate that iron is taken up by Emiliania in a
      time and concentration dependent manner consistent with an active transport
      process. Based on inhibitor studies it appears that iron is taken up directly as
      Fe(iii). However if a reductive step is involved the Fe(II) must not be
      accessible to the external environment. Upon long term exposure to (57)Fe we have
      been able, using a combination of Mossbauer and XAS spectroscopies, to identify a
      single metabolite which displays spectral features similar to the phosphorus-rich
      mineral core of bacterial and plant ferritins.

PMID- 23011579
TI  - Variations in the course of the maxillary artery in Japanese adults.
AB  - Many authors have studied variation in the maxillary artery but there have been
      inconsistencies between reported observations. The present research aimed to
      examine the courses and branching patterns of the trunk and branches of the
      maxillary artery in a large sample of Japanese adult cadavers. The course of the
      maxillary artery should be reclassified into seven groups as a clear relationship
      was found between the origin of the middle meningeal artery and the course of the
      maxillary artery. This indicates that conventional theory about the formation of
      the maxillary artery, which was considered to be a direct derivative of the
      stapedial artery, might be inaccurate. Many variations in the origin of the
      inferior alveolar artery were found. Notably, the inferior alveolar artery origin
      from the external carotid artery and a double origin of the inferior alveolar
      artery was also observed. Thus, the maxillary artery might be derived from a
      combination of both the external carotid and stapedial arteries.

PMID- 23011580
TI  - Photophysical properties of MM quadruply bonded complexes (M = Mo, W) supported
      by carboxylate ligands: charge delocalization and dynamics in S1 and T1 states.
AB  - Quadruply bonded dinuclear metal complexes of molybdenum and tungsten have the MM
      configuration sigma(2)pi(4)delta(2) and a considerable degree of attention has
      been devoted to studies of the delta -> delta(*) transition. For compounds of the
      type M(2)(O(2)CR)(4), the CO(2) pi(*) orbitals introduce a M(2) delta to ligand
      pi(*) transition, a (1)MLCT absorption which may be lower in energy than the
      delta -> delta(*) and is more intense, thus obscuring the observation of the
      latter. When the R group is a conjugated organic system such as an aryl group,
      the (1)MLCT shifts to even lower energy and emission is seen from this S(1) state
      in addition to phosphorescence from the T(1) state which may be either (3)MLCT or
      (3)MMdeltadelta(*). The latter typically occurs around 1100 nm with a lifetime
      that ranges from ~1 MUs (M = W) to 100 MUs (M = Mo). The S(1)(1)MLCT states have
      lifetimes of ~1-20 ps, allowing for fs and ns studies of the charge
      distribution/localization with time in both the S(1) and T(1) states, which is
      quite rare for transition metal coordination complexes. Of particular interest
      and focus have been complexes of the type trans-M(2)L(2)L'(2) where L and L' are
      carboxylate or amidinate groups for which only one set of ligands allows for
      expansive Lpi-M(2)delta-Lpi conjugation and has a low energy (1)MLCT. Compounds
      of this type have excited states that may be considered as mixed valence (MV)
      ions [L-M(2)(+)-L(-)] <-> [L(-)-M(2)(+)-L] where the hole resides on the M(2)
      unit and the electron is either localized on one ligand, a class I or II MV ion,
      or is fully delocalized over both ligands, a class III ion in the Robin and Day
      scheme. Examples of these systems will be described along with the newly prepared
      complexes trans-M(2)(T(i)PB)(2)(O(2)CC=C-9-anthracene)(2), M = Mo, W, that have
      the IR-active reporter groups CO(2) and C=C.

PMID- 23011581
TI  - Opening wedge distal femoral varus osteotomy using the Puddu plate and calcium
      phosphate bone cement.
AB  - PURPOSE: The goal of this study was to document the outcome at midterm follow-up
      of 19 patients treated for lateral osteoarthritis of the knee between 1999 and
      2007. It was our hypothesis that the results and complication rate would be
      comparable to or better than those reported in the literature for closing wedge
      or alternative open wedge techniques. METHODS: All patients underwent an open
      wedge distal femoral varisation osteotomy using the Puddu plate system combined
      with calcium phosphate injection into the defect. Knee Society Knee Score and
      Kellgren-Lawrence osteoarthritis score were assessed preoperatively and at final
      follow-up. RESULTS: The average knee score improved significantly from 43 +/- 8
      preoperatively to 78 +/- 23 at final follow-up. The Kellgren-Lawrence
      osteoarthritis score remained unchanged. Kaplan-Meier analysis using revision
      surgery or conversion to TKA as an endpoint demonstrated an 82% successful
      survivorship at 7 years of follow-up. CONCLUSION: Based upon these results, we
      believe that a distal femoral varisation osteotomy using the Puddu plate and
      injectable bone cement is an equivalent treatment option compared to closing
      wedge techniques and leading to good results at midterm follow-up in patients
      with lateral gonarthrosis and valgus alignment. LEVEL OF EVIDENCE: IV.

PMID- 23011582
TI  - Arthroscopic treatment in mild to moderate osteoarthritis of the ankle.
AB  - PURPOSE: This study was designed to review the outcomes of patients who have
      undergone arthroscopic treatment for mild to moderate ankle osteoarthritis and to
      determine the factors associated with unsuccessful outcomes. METHODS: A total of
      63 patients (mean age, 53.7 +/- 16 years) with mild to moderate ankle
      osteoarthritis who underwent arthroscopic treatment were analysed. We
      investigated the possible correlations between the clinicopathologic features and
      clinical outcomes using the visual analogue scale for pain and American
      Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score and analysed the
      data to clarify the effect of prognostic factors on clinical outcome. RESULTS:
      Visual analogue scale and AOFAS scores were improved after surgery for up to 2
      years (p < 0.0001). The largest improvements in clinical scores were observed
      after 6 months, and thereafter, they steadily declined. Body mass index (BMI) (p
      = 0.011) and presence of associated intra-articular lesions (p = 0.002) showed a
      significant correlation with the clinical outcome. There was no association
      between outcome and the patient's age, gender, duration of symptoms, type of
      osteoarthritis, treatment modality and coronal alignment (n.s.). CONCLUSION:
      Arthroscopic treatment for mild to moderate ankle osteoarthritis has a favourable
      outcome in selected patients. BMI and associated intra-articular lesion are
      significant risk factors for poor outcome.

PMID- 23011583
TI  - Excellent results of lesser tuberosity transfer in acute locked posterior
      shoulder dislocation.
AB  - PURPOSE: The aim of the present study was to evaluate the clinical and
      radiological results of lesser tuberosity transfer in acute locked posterior
      shoulder dislocation with a humeral head defect between 25 and 45 %. METHODS:
      Clinical and radiological results of seven patients with locked posterior
      shoulder dislocation with a humeral head defect between 25 and 45 % which were
      managed with a modification of the McLaughlin procedure within 14 days after
      injury were evaluated retrospectively after a mean follow-up of 41 months.
      RESULTS: All shoulders remained stable. The results were good in one and
      excellent in six patients with a median absolute Constant score of 92 (range 80
      98). Mean active pain-free abduction was 171.4 degrees  (SD 6.4), mean flexion
      was 175.7 degrees  (SD 4.9), and mean external rotation was 54.3 degrees  (SD
      17.6). Internal rotation was restricted in all patients. There were no
      radiological signs of osteoarthritis. CONCLUSIONS: Lesser tuberosity transfer
      shows excellent clinical and radiographic mid-term results in acute cases of
      locked posterior shoulder dislocation with a reverse Hill-Sachs lesion between 25
      and 45 %.

PMID- 23011584
TI  - What is the effect of the early weight-bearing mobilisation without using any
      support after endoscopy-assisted Achilles tendon repair?
AB  - PURPOSE: The aim of this study was to assess the effect of immediate weight
      bearing mobilisation with intensive rehabilitation on muscle strength and lower
      extremity functional level after endoscopy-assisted Achilles tendon repairs.
      METHODS: After warming up for 5 min at a self-selected intensity on a stationary
      bike 32 male patients were tested for bilateral peak concentric isokinetic ankle
      dorsi- and plantar-flexor torque, passive range of motion for ankle joint, one
      leg hop for distance, single-leg vertical jump height, Achilles Tendon Total
      Rupture Score, and perceived function using the Foot and Ankle Outcome Score
      (FAOS). A series of paired sample t tests were used to compare side-to-side
      differences (p < 0.05). RESULTS: There were no significant differences in hop and
      jump tests, dorsi- and plantar-flexor isokinetic muscle strength, and dorsi- and
      plantar-flexion range of motion between the affected and unaffected side of the
      patients. Pain score of FAOS was 95 +/- 8, other symptoms score was 92 +/- 11,
      function in daily living score was 95 +/- 6, function in sport and recreation was
      85 +/- 16, and Quality of Life score was 85 +/- 12. The mean of the Achilles
      Tendon Rupture Score was 86. CONCLUSIONS: There was no significant difference in
      both ankle muscle strength and lower extremity functional level between the
      endoscopy-assisted repairs and the unaffected sides. The early tolerated weight
      bearing mobilisation without cast-brace and/or special shoe at the first day
      after the surgery may easily provide to return the daily living activities. It
      improves muscle strength, functional level, and range of motion. Further
      comprehensive and prospective studies on large patients should be warranted to
      analyse and compare the clinical and functional results in patients with
      endoscopy-assisted Achilles tendon repair.

PMID- 23011585
TI  - Association of iniencephaly, anencephaly, and fusion of cervical vertebral
      bodies:  a new autosomal recessive syndrome?

PMID- 23011586
TI  - Torsades de Pointes in the Guinea-pig heart : editorial to: "dofetilide promotes
      repolarization abnormalities in perfused Guinea-pig heart" by O.E. Osadchii.

PMID- 23011587
TI  - Resistance evolution to the first generation of genetically modified Diabrotica
      active Bt-maize events by western corn rootworm: management and monitoring
      considerations.
AB  - Western corn rootworm (Diabrotica virgifera virgifera; WCR) is a major
      coleopteran maize pest in North America and the EU, and has traditionally been
      managed through crop rotation and broad-spectrum soil insecticides. Genetically
      modified Bt-maize offers an additional management tool for WCR and has been
      valuable in reducing insecticide use and increasing farm income. A concern is
      that the widespread, repeated, and exclusive deployment of the same Bt-maize
      transformation event will result in the rapid evolution of resistance in WCR.
      This publication explores the potential of WCR to evolve resistance to plant
      produced Bt-toxins from the first generation of Diabrotica-active Bt-maize events
      (MON 863 and MON 88017, DAS-59122-7 and MIR604), and whether currently
      implemented risk management strategies to delay and monitor resistance evolution
      are appropriate. In twelve of the twelve artificial selection experiments
      reported, resistant WCR populations were yielded rapidly. Field-selected
      resistance of WCR to Cry3Bb1 is documented in some US maize growing areas, where
      an increasing number of cases of unexpected damage of WCR larvae to Bt-maize MON
      88017 has been reported. Currently implemented insect resistance management
      measures for Bt-crops usually rely on the high dose/refuge (HDR) strategy.
      Evidence (including laboratory, greenhouse and field data) indicates that several
      conditions contributing to the success of the HDR strategy may not be met for the
      first generation of Bt-maize events and WCR: (1) the Bt-toxins are expressed
      heterogeneously at a low-to-moderate dose in roots; (2) resistance alleles may be
      present at a higher frequency than initially assumed; (3) WCR may mate in a non
      random manner; (4) resistance traits could have non-recessive inheritance; and
      (5) fitness costs may not necessarily be associated with resistance evolution.
      However, caution must be exercised when extrapolating laboratory and greenhouse
      results to field conditions. Model predictions suggest that a 20 % refuge of non
      Diabrotica-active Bt-maize can delay resistance evolution in WCR under certain
      conditions. This publication concludes that further research is needed to resolve
      the remaining scientific uncertainty related to the appropriateness of the HDR in
      delaying resistance evolution in WCR, resistance monitoring is essential to
      detect early warning signs indicating resistance evolution in the field, and that
      integrated pest management reliant on multiple tactics should be deployed to
      ensure effective long-term corn rootworm management and sustainable use of Bt
      maize.

PMID- 23011590
TI  - Comparative analysis of monocytic and granulocytic myeloid-derived suppressor
      cell subsets in patients with gastrointestinal malignancies.
AB  - Myeloid-derived suppressor cells (MDSC) are a heterogenous population of cells
      comprising myeloid progenitor cells and immature myeloid cells, which have the
      ability to suppress the effector immune response. In humans, MDSC have not been
      well characterized owing to the lack of specific markers, although it is possible
      to broadly classify the MDSC phenotypes described in the literature as being
      predominantly granulocytic (expressing markers such as CD15, CD66, CD33) or
      monocytic (expressing CD14). In this study, we set out to perform a direct
      comparative analysis across both granulocytic and monocytic MDSC subsets in terms
      of their frequency, absolute number, and function in the peripheral blood of
      patients with advanced GI cancer. We also set out to determine the optimal method
      of sample processing given that this is an additional source of heterogeneity.
      Our findings demonstrate consistent changes across sample processing methods for
      monocytic MDSC, suggesting that reliance upon cryopreserved PBMC is acceptable.
      Although we did not see an increase in the population of granulocytic MDSC, these
      cells were found to be more suppressive than their monocytic counterparts.

PMID- 23011589
TI  - Low-dose cyclophosphamide administered as daily or single dose enhances the
      antitumor effects of a therapeutic HPV vaccine.
AB  - Although therapeutic HPV vaccines are able to elicit systemic HPV-specific
      immunity, clinical responses have not always correlated with levels of vaccine
      induced CD8(+) T cells in human clinical trials. This observed discrepancy may be
      attributable to an immunosuppressive tumor microenvironment in which the CD8(+) T
      cells are recruited. Regulatory T cells (Tregs) are cells that can dampen
      cytotoxic CD8(+) T-cell function. Cyclophosphamide (CTX) is a systemic
      chemotherapeutic agent, which can eradicate immune cells, including inhibitory
      Tregs. The optimal dose and schedule of CTX administration in combination with
      immunotherapy to eliminate the Treg population without adversely affecting
      vaccine-induced T-cell responses is unknown. Therefore, we investigated various
      dosing and administration schedules of CTX in combination with a therapeutic HPV
      vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a
      single preconditioning dose or a daily dose of CTX in combination with the
      pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in
      combination with vaccine had a synergistic antitumor effect as compared to
      monotherapy alone. The potent antitumor responses were attributed to the
      reduction in Treg frequency and increased infiltration of HPV16 E7-specific
      CD8(+) T cells, which led to higher ratios of CD8(+)/Treg and CD8(+)/CD11b(+)Gr
      1(+) myeloid-derived suppressor cells (MDSCs). There was an observed trend toward
      decreased vaccine-induced CD8(+) T-cell frequency with daily dosing of CTX. We
      recommend a single, preconditioning dose of CTX prior to vaccination due to its
      efficacy, ease of administration, and reduced cumulative adverse effect on
      vaccine-induced T cells.

PMID- 23011591
TI  - Methylphenidate-mediated reduction in prefrontal hemodynamic responses to working
      memory task: a functional near-infrared spectroscopy study.
AB  - OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) is a non-invasive
      optical technique for bedside evaluation of cerebral metabolism that has clinical
      potential for monitoring the efficacy of pharmacological treatment. In this pilot
      study, we investigated the cognitive effects of methylphenidate (MP) on
      prefrontal function using fNIRS in healthy subjects. METHODS: Thirteen right
      handed healthy subjects underwent working memory tasks (0-back and 2-back) after
      a single oral dose of MP (20 mg) or placebo administered in a double-blind
      crossover design on two different days separated by 1-3 days. We measured changes
      in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) concentrations during
      the tasks in bilateral prefrontal regions after MP or placebo administration
      using two-channel fNIRS. RESULTS: There were significantly more correct responses
      and fewer missed responses during the 2-back task performance after MP treatment
      as compared with placebo. Baseline-corrected oxy-Hb was significantly decreased
      after MP treatment compared with the placebo in the 2-back task in the right
      frontal region but was not different in the 0-back task. Baseline-corrected deoxy
      Hb and total-Hb concentrations were not significant between MP and placebo
      conditions in either of the cognitive tasks. CONCLUSIONS: These data are
      consistent with previous positron emission tomography findings of MP-mediated
      reduction in lateral prefrontal activity accompanied by improved cognitive
      performance.

PMID- 23011592
TI  - Neuropeptide Y1 receptor in immune cells regulates inflammation and insulin
      resistance associated with diet-induced obesity.
AB  - Recruitment of activated immune cells into white adipose tissue (WAT) is linked
      to the development of insulin resistance and obesity, but the mechanism behind
      this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells
      controls inflammation and insulin resistance in obesity. Selective deletion of Y1
      receptors in the hematopoietic compartment of mice leads to insulin resistance
      and inflammation in WAT under high fat-fed conditions. This is accompanied by
      decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and
      an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In
      vitro, activated Y1-deficient intraperitoneal macrophages display an increased
      inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis
      factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates
      the release of these cytokines, this effect being blocked by Y1 but not Y2
      receptor antagonism. Importantly, treatment of adipocytes with the supernatant of
      activated Y1-deficient macrophages causes insulin resistance, as demonstrated by
      decreased insulin-induced phosphorylation of the insulin receptor and Akt as well
      as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in
      hematopoietic-derived cells such as macrophages is critical for the control of
      inflammation and insulin resistance in obesity.

PMID- 23011593
TI  - Receptor for advanced glycation end products regulates adipocyte hypertrophy and
      insulin sensitivity in mice: involvement of Toll-like receptor 2.
AB  - Receptor for advanced glycation end products (RAGE) has been shown to be involved
      in adiposity as well as atherosclerosis even in nondiabetic conditions. In this
      study, we examined mechanisms underlying how RAGE regulates adiposity and insulin
      sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene
      transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small
      interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double
      knockdown of high mobility group box-1 and S100b, both of which are RAGE ligands
      endogenously expressed in 3T3-L1 cells, also canceled RAGE-medicated adipocyte
      hypertrophy, implicating a fundamental role of ligands-RAGE ligation. Adipocyte
      hypertrophy induced by RAGE overexpression is associated with suppression of
      glucose transporter type 4 and adiponectin mRNA expression, attenuated insulin
      stimulated glucose uptake, and insulin-stimulated signaling. Toll-like receptor
      (Tlr)2 mRNA, but not Tlr4 mRNA, is rapidly upregulated by RAGE overexpression,
      and inhibition of Tlr2 almost completely abrogates RAGE-mediated adipocyte
      hypertrophy. Finally, RAGE(-/-) mice exhibited significantly less body weight,
      epididymal fat weight, epididymal adipocyte size, higher serum adiponectin
      levels, and higher insulin sensitivity than wild-type mice. RAGE deficiency is
      associated with early suppression of Tlr2 mRNA expression in adipose tissues.
      Thus, RAGE appears to be involved in mouse adipocyte hypertrophy and insulin
      sensitivity, whereas Tlr2 regulation may partly play a role.

PMID- 23011594
TI  - Interaction between the central and peripheral effects of insulin in controlling
      hepatic glucose metabolism in the conscious dog.
AB  - The importance of hypothalamic insulin action to the regulation of hepatic
      glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is
      unknown. Thus, we assessed the role of central insulin action in the response of
      the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic
      clamp, hepatic portal vein insulin delivery was increased three- or eightfold in
      the conscious dog. Insulin action was studied in the presence or absence of
      intracerebroventricularly mediated blockade of hypothalamic insulin action.
      Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular
      and metabolic aspects of insulin action were assessed. Blockade of hypothalamic
      insulin signaling did not alter the insulin-mediated suppression of hepatic
      gluconeogenic gene transcription but blunted the induction of glucokinase gene
      transcription and completely blocked the inhibition of glycogen synthase kinase
      3beta gene transcription. Thus, central and peripheral insulin action combined to
      control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of
      hypothalamic insulin action did not alter the effects of the hormone on hepatic
      glucose flux (production or uptake). These data indicate that brain insulin
      action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose
      metabolism caused by normal physiologic hyperinsulinemia in this large animal
      model.

PMID- 23011595
TI  - Otitis media in infancy and the development of asthma and atopic disease.
AB  - Otitis media is a frequent respiratory infection of early childhood and it is
      important to fully understand the long-term complications and sequelae.
      Literature examining otitis media in early childhood and subsequent development
      of atopic disease is sparse despite there being vast literature on the
      association between respiratory infections and atopic disease. Current data
      support the hypothesis that otitis media infections in early life, especially
      frequent or severe infections, influence the developing immune system, resulting
      in increased risk for asthma. Recent findings have also reported an association
      between otitis media and eczema. Atopic children and those with a family history
      of atopy appear to be at greater risk. Future work should investigate the
      specific mechanisms involved. It is possible that vaccines and preventive
      strategies aimed at reducing the burden of otitis media could also reduce the
      burden of childhood asthma and atopic disease.

PMID- 23011596
TI  - Treatment of acute otitis media in young children.
AB  - Although acute otitis media (AOM) is one of the most common pediatric problems,
      the debate over treatment, especially in young children, continues. The 2004
      Guideline on treatment of AOM stated that observation without antimicrobial
      therapy was an option for selected children 6-24 months of age with AOM. Two
      recent randomized trials sought to determine the necessity of antimicrobial
      treatment in young children; both studies found modest, statistically
      significant, positive effects of treatment. However, these studies provoked a
      flurry of discussion in the literature and the issue remains unsettled. That
      prevention is preferable to treatment is not controversial. Eliminating or
      modifying risk factors and use of vaccines, both bacterial and viral, may help
      decrease the number of AOM episodes. The discussion on treatment of AOM in young
      children must also take into account side effects of treatment and effect of
      treatment on possible long-lasting sequelae of AOM, such as developmental
      outcomes.

PMID- 23011597
TI  - Rationale and feasibility of intranasal delivery of drugs to the eustachian tube
      orifice.
AB  - Intranasal medication for eustachian tube dysfunction (ETD) is an established
      practice in otolaryngology through the effects of steroids, decongestants,
      antihistamines or a combination of the above in reducing tubal oedema. The author
      has previously argued that a double-blind, randomised control trial would be
      helpful in determining effectiveness of treatment, if a standardised head
      position, chiefly Mygind or Ragan, was adopted to maximise intranasal drop
      delivery into the eustachian tube orifice. One recent paper suggests that
      intranasal treatment is not very effective, but ultimately does not state whether
      a standardised head position was adopted. Although a large body of evidence
      supports the hypothesis that the nasal passages are the route to middle ear
      disease, there is as yet no paper that has been published that has specifically
      addressed this issue, therefore the author must conclude that evidence to support
      intranasal treatment for ETD is still lacking and further research is desirable.

PMID- 23011598
TI  - Allergen component testing for food allergy: ready for prime time?
AB  - Food allergies can cause life-threatening reactions and greatly influence quality
      of life. Accurate diagnosis of food allergies is important to avoid serious
      allergic reactions and prevent unnecessary dietary restrictions, but can be
      difficult. Skin prick testing (SPT) and serum food-specific IgE (sIgE) levels are
      extremely sensitive testing options, but positive test results to tolerated foods
      are not uncommon. Allergen component-resolved diagnostics (CRD) have the
      potential to provide a more accurate assessment in diagnosing food allergies.
      Recently, a number of studies have demonstrated that CRD may improve the
      specificity of allergy testing to a variety of foods including peanut, milk, and
      egg. While it may be a helpful adjunct to current diagnostic testing, CRD is not
      ready to replace existing methods of allergy testing, as it not as sensitive, is
      not widely available, and evaluations of component testing for a number of major
      food allergens are lacking.

PMID- 23011599
TI  - Coupling between feedback loops in autoregulatory networks affects bistability
      range, open-loop gain and switching times.
AB  - Biochemical regulatory networks governing diverse cellular processes such as
      stress-response, differentiation and cell cycle often contain coupled feedback
      loops. We aim at understanding how features of feedback architecture, such as the
      number of loops, the sign of the loops and the type of their coupling, affect
      network dynamical performance. Specifically, we investigate how bistability
      range, maximum open-loop gain and switching times of a network with
      transcriptional positive feedback are affected by additive or multiplicative
      coupling with another positive- or negative-feedback loop. We show that a
      network's bistability range is positively correlated with its maximum open-loop
      gain and that both quantities depend on the sign of the feedback loops and the
      type of feedback coupling. Moreover, we find that the addition of positive
      feedback could decrease the bistability range if we control the basal level in
      the signal-response curves of the two systems. Furthermore, the addition of
      negative feedback has the capacity to increase the bistability range if its
      dissociation constant is much lower than that of the positive feedback. We also
      find that the addition of a positive feedback to a bistable network increases the
      robustness of its bistability range, whereas the addition of a negative feedback
      decreases it. Finally, we show that the switching time for a transition from a
      high to a low steady state increases with the effective fold change in gene
      regulation. In summary, we show that the effect of coupled feedback loops on the
      bistability range and switching times depends on the underlying mechanistic
      details.

PMID- 23011600
TI  - [Dilated cardiomyopathy].
AB  - Dilated cardiomyopathy (DCM) has a familial accumulation in 20-50% of cases and,
      therefore, frequently has a genetic cause. Currently, numerous mutations are
      known in more than 40 genes, which account for around 20% of familial cases. The
      structured evaluation of family history with recording of a family tree is an
      obligatory part of the initial diagnosis of DCM. By evaluation of family members
      other persons at risk can be identified. With the exception of the lamin A/C gene
      (LMNA), genetic testing does not allow risk stratification. DCM caused by LMNA
      mutations is associated with a high risk of sudden cardiac death. In cases of
      familial conduction disease, sudden cardiac death and a concomitant muscle
      disease LMNA mutation should be excluded. Implantation of an ICD is indicated if
      the LVEF is chronically less than 35% independent from etiology. This applies
      with some restrictions for asymptomatic patients in NYHA class I. Patients should
      receive optimal drug therapy for 3-12 months before ICD implantation.

PMID- 23011601
TI  - Arrhythmogenic right ventricular cardiomyopathy: an update on pathophysiology,
      genetics, diagnosis, and risk stratification.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited
      cardiomyopathy accounting for life-threatening ventricular tachyarrhythmias and
      sudden death in young individuals and athletes. Over the past years, mutations in
      desmosomal genes have been identified as disease-causative. However, genetic
      heterogeneity and variable phenotypic expression alongside with diverse disease
      progression still render the evaluation of its prognostic implication difficult.
      ARVC was initially entered into the canon of cardiomyopathies of the World Health
      Organization in 1995, and international efforts have resulted in the 2010
      modified diagnostic criteria for ARVC. Despite all additional insights into
      pathophysiology, clinical management, and modern risk stratification, under
      /misdiagnosing of ARVC remains a problem and hampers reliable statements on the
      incidence, prevalence, and natural course of the disease.This review provides a
      comprehensive overview of the current literature on the pathogenesis, diagnosis,
      treatment, and prognosis of ARVC and sheds some light on potential new
      developments in these areas.

PMID- 23011602
TI  - Strategies for improving the clinical benefit of antiangiogenic drug based
      therapies for breast cancer.
AB  - Viewed as a whole, the aggregate outcomes of a number of positive randomized
      phase III clinical trial results evaluating the VEGF-pathway targeting
      antiangiogenic drug bevacizumab, with or without concurrent chemotherapy, in
      metastatic breast cancer patients have been disappointingly modest. In the case
      of antiangiogenic tyrosine kinase inhibitors (TKIs) the results have been
      negative. Nevertheless, several findings indicate antiangiogenic drugs,
      especially bevacizumab, are active and can lead to demonstrable clinical benefit
      in some patients, thus stimulating research into developing strategies to
      significantly improve their efficacy and reduce toxicity. Some of these
      initiatives include: 1) discovery and validation of predictive markers that can
      prospectively identify patients more likely to benefit from antiangiogenic
      therapy; 2) recognition that the nature of the chemotherapy partner or backbone
      can strongly impact outcomes when combined with antiangiogenic drugs such as
      bevacizumab, and thus developing what may be improved combination chemotherapy
      partner regimens, e.g. metronomic chemotherapy; 3) evaluating prospectively in
      more depth whether subtypes of the disease-especially triple negative or
      inflammatory breast cancer-are more responsive to antiangiogenic therapy than
      other subtypes; 4) evaluating new agents that inhibit angiogenesis in a VEGF
      independent manner and other types of drug that can be effectively combined with
      antiangiogenics, e.g. c-met inhibitors; 5) uncovering the basis of resistance or
      relapse/progression on the therapy with antiangiogenic drugs; 6) development of
      improved predictive preclinical breast cancer models for therapy testing, e.g.
      treatment of mice with established multi-organ breast cancer metastatic disease
      or genetically engineered mouse models of breast cancer, or mice bearing patient
      derived breast cancer tissue xenografts.

PMID- 23011603
TI  - Translating mathematical modeling of tumor growth patterns into novel therapeutic
      approaches for breast cancer.
AB  - In breast cancer, mortality is driven by the metastatic process, whereby some
      cancer cells leave their primary site of origin and travel to distant vital
      organs. Despite improved screening and therapies to treat breast cancers,
      metastasis continues to undermine these advances. The pervasive albatross of
      metastasis necessitates improved prevention and treatment of metastasis. To this
      end, clinicians routinely employ post-operative or adjuvant therapy to decrease
      the risk of future metastasis and improve the chance for cure. This article
      evaluates the limitations of breast cancer therapies within the context of growth
      curves, and in doing so, provides new insight into the metastatic process as well
      as more effective means for therapeutic delivery. Two critical developments
      evolve from this mathematical analysis: first, the use of dose dense chemotherapy
      to improve survival among breast cancer patients; and second, the theory of self
      seeding, which fundamentally changes our understanding of metastasis and the
      trajectory of drug development.

PMID- 23011604
TI  - Protein predictive signatures for lymph node metastasis of gastric cancer.
AB  - Lymph node status remains one of most crucial indicators of gastric cancer
      prognosis and treatment planning. Current imaging methods have limited accuracy
      in predicting lymph node metastasis. We sought to identify protein markers in
      primary gastric cancer and to define a risk model to predict lymph node
      metastasis. The Protein Pathway Array (PPA) (initial selection) and Western blot
      (confirmation) were used to assess the protein expression in a total of 190
      freshly frozen gastric cancer samples. The protein expression levels were
      compared between samples with lymph node metastasis (n = 73) and those without
      lymph node metastasis (n = 57) using PPA. There were 27 proteins differentially
      expressed between lymph node positive samples and lymph node negative samples.
      Five proteins (Factor XIII B, TFIIH p89, ADAM8, COX-2 and CUL-1) were identified
      as independent predictors of lymph node metastasis. Together with
      vascular/lymphatic invasion status, a risk score model was established to
      determine the risk of lymph node metastasis for each individual gastric cancer
      patient. The ability of this model to predict lymph node metastasis was further
      confirmed in a second cohort of gastric cancer patients (33 with and 27 without
      lymph node metastasis) using Western blot. This study indicated that some
      proteins differentially expressed in gastric cancer can be selected as clinically
      useful biomarkers. The risk score model is useful for determining patients' risk
      of lymph node metastasis and prognosis.

PMID- 23011605
TI  - [Diabetic retinopathy and diabetic foot syndrome in patients of a sub-Saharan
      megacity (Kinshasa, DR Congo)].
AB  - PURPOSE: The prevalence of diabetes mellitus is increasing worldwide especially
      in developing countries. Foot ulcerations in patients with diabetic neuropathy
      have a high impact in the overall amputation rate. In the present study we looked
      for the severity of diabetic retinopathy in patients with diabetic foot syndrome
      in a diabetic care unit in a sub-Sahara megacity (Kinshasa, Democratic Republic
      of Congo). METHOD: Forty-one patients with diabetes-related foot ulcerations (26
      male, 15 female, mean age 45.6 years) were enrolled in the study. All patients
      underwent visual acuity evaluation and slit lamp biomicroscopy. Incidence and
      stage of retinopathy were evaluated by retinal funduscopy and documented by
      fundus photography. RESULTS: Twenty-seven eyes showed no signs of diabetic
      retinopathy. Forty-seven eyes were diagnosed as non-proliferative diabetic
      retinopathy (16 mild, 16 moderate, 15 severe). Seven eyes showed proliferative
      diabetic retinopathy. One patient had a unilateral central venous occlusion. In
      this case the classification of diabetic retinopathy was not possible because of
      the massive retinal bleedings. CONCLUSION: It was evident that there is a
      considerable discrepancy between partly extensive foot ulcerations and only mild
      to moderate diabetic retinopathy in most of the patients. This indicates that
      neuropathy-induced foot problems and microangiopathy-induced diabetic retinopathy
      are diabetic complications whose formal pathogenesis is only loosely correlated.
      Additional risk factors in local African conditions compared to Europe may play a
      major role in this discrepancy.

PMID- 23011606
TI  - [Reversible unilateral blindness].

PMID- 23011607
TI  - [A Roman orbital implant?].
AB  - During an excavation in Regensburg/Germany the skeleton of an approximately 20
      year-old Roman man was found who was buried in the 3rd/4th century after Christ.
      A "stone" was found which fitted into the left orbit precisely. After a thorough
      investigation of the "stone" and with the ophthalmohistorical literature in mind
      an orbital "implant" as well as a petrified medical paste ("Kollyrium") could be
      ruled out almost with certainty. Possibly the "stone" served another medical
      purpose or was used for protection of the eye.

PMID- 23011609
TI  - Theoretical study of the solvatochromism of a donor-acceptor bithiophene.
AB  - The solvation and the solvatochromic behavior of the 5-(methylthio)-5'-nitro-2,2'
      bithiophene 1 in diethyl ether, dichloromethane, acetonitrile, methanol and
      formamide was theoretically investigated with an iterative molecular and quantum
      mechanics (QM/MM) approach. Calculated longest-wavelength solvatochromic
      absorption band of 1, obtained as averages of statistically uncorrelated
      configurations, including the solute and explicit solvent molecules of the first
      and second solvation layer, were in excellent agreement with the experimental
      results.

PMID- 23011608
TI  - Molecular dynamics analysis of a series of 22 potential farnesyltransferase
      substrates containing a CaaX-motif.
AB  - Protein farnesyltransferase (FTase) is an important target in many research
      fields, more markedly so in cancer investigation since several proteins known to
      be involved in human cancer development are thought to serve as substrates for
      FTase and to require farnesylation for proper biological activity. Several FTase
      inhibitors (FTIs) have advanced into clinical testing. Nevertheless, despite the
      progress in the field several functional and mechanistic doubts on the FTase
      catalytic activity have persisted. This work provides some crucial information on
      this important enzyme by describing the application of molecular dynamics
      simulations using specifically designed molecular mechanical parameters for a
      variety of 22 CaaX peptides known to work as natural substrates or inhibitors for
      this enzyme. The study involves a comparative analysis of several important
      molecular aspects, at the mechanistic level, of the behavior of substrates and
      inhibitors at the dynamic level, including the behavior of the enzyme and
      peptides, as well as their interaction, together with the effect of the solvent.
      Properties evaluated include the radial distribution function of the water
      molecules around the catalytically important zinc metal atom and cysteine sulfur
      of CaaX, the conformations of the substrate and inhibitor and the corresponding
      RMSF values, critical hydrogen bonds, and several catalytically relevant
      distances. These results are discussed in light of recent experimental and
      computational evidence that provides new insights into the activity of this
      enzyme.

PMID- 23011610
TI  - Molecular dipole effects on tuning electron transfer in a porphine-quinone
      complex: a DFT and TDDFT study.
AB  - The effect of a strong electric field generated by molecular dipoles on the
      ground state electronic structure and the Q and B states as well as the lowest
      charge transfer (CT) excited state of porphine-2,5-dimethyl-1,4-benzoquinone (PQ)
      complex has been investigated theoretically. Density functional theory DFT and
      time-dependent DFT (TDDFT) with the BH&HLYP hybrid functional have been applied
      in these calculations. The molecular dipole effect was generated by imposing one
      or two helical homopeptides consisting of eight alpha-aminoisobutyric acid
      residues (Aib(8)) close to the PQ complex. The molecular dipoles in a close
      proximity to the PQ complex expose it to an electric field of the order of
      magnitude of 10(9) V/m. The presence of the ambient molecular dipoles affects
      mainly the energy of the lowest CT state and barely the energies of the Q and B
      states. The molecular dipoles affect the energies of the excited states in a
      similar way as an external electrostatic field. Hence, the electric field induced
      by the molecular dipoles of the helical peptides could be used analogously to the
      external electrostatic field to control electron transfer (ET) in the PQ complex.

PMID- 23011611
TI  - Sonographically guided enema for intussusception reduction: a safer alternative
      to fluoroscopy.

PMID- 23011612
TI  - Sonography first for subcutaneous abscess and cellulitis evaluation.

PMID- 23011613
TI  - Sonography in the treatment of calcific tendinitis of the rotator cuff.

PMID- 23011614
TI  - Use of ultrasound guidance improves central venous catheter insertion success
      rates among junior residents.
AB  - OBJECTIVES: The purpose of this study was to determine whether junior residents
      had higher rates of first cannulation and overall success at central venous
      catheter insertions with the use of ultrasound (US) guidance compared to the
      landmark technique. METHODS: We conducted a secondary analysis of data from a
      prospective randomized controlled study of junior residents from January 2007
      through September 2008, which assessed the impact of simulation training on
      central venous catheter insertion success rates. Blinded independent raters
      observed in-hospital central venous catheter insertions using a procedural
      checklist. Success at first cannulation and successful insertion were the primary
      outcomes. Secondary outcomes included rates of technical errors and mechanical
      complications. RESULTS: Independent raters observed 480 central venous catheter
      insertions by 115 residents. Successful first cannulation occurred in 27% of
      landmark compared to 49% of dynamic US-guided (P < .01), and 50% of static US
      guided (P = .01) cannulations. Insertion success occurred for 55% of landmark
      compared to 80% of dynamic US-guided (P < .01) and 80% of static US-guided (P <
      .01) cannulations. Dynamic US guidance was associated with increased odds of
      first cannulation success compared to the landmark technique (odds ratio [OR],
      2.24; 95% confidence interval [CI], 1.37-3.67) and successful insertion (OR,
      3.80; 95% CI, 2.34-6.19). Static US guidance was associated with increased odds
      of first cannulation success compared to the landmark technique (OR, 2.59; 95%
      CI, 1.25-5.39) and successful insertion (OR, 3.48; 95% CI, 1.54-7.87). The
      results were independent of central venous catheter insertion training, patient
      comorbidities, and resident specialties. There was no difference related to
      mechanical complications between the procedures. CONCLUSIONS: Dynamic and static
      US guidance during central venous catheter insertion was associated with improved
      in-hospital first cannulation rates and overall success rates of insertions by
      junior residents.

PMID- 23011615
TI  - Detection of free intraperitoneal fluid in healthy young men.
AB  - OBJECTIVES: Free intraperitoneal fluid is a secondary sign of abdominal
      disorders. The detection of small volumes of fluid has been documented as a
      normal finding in women of childbearing age and also in pediatric sonography.
      However, the finding of free fluid in asymptomatic men has not been similarly
      documented by sonography. We postulate that with high-frequency linear probes,
      small volumes of fluid may be detected in asymptomatic men without underlying
      abdominal disorders. METHODS: Ten healthy male volunteers underwent targeted
      abdominal sonographic examinations after an overnight fast and in an immediate
      postprandial state. The findings were documented, and representative images were
      saved for analysis. RESULTS: We found small slivers or geometric collections of
      fluid between bowel loops in 4 of the 10 volunteers. No obvious correlation
      between the detection of fluid and the nutritional or hydration status of the
      patient was identified. CONCLUSIONS: The findings suggest that small volumes of
      pelvic free fluid in healthy men can be normal and do not necessarily indicate
      underlying disorders. The role of free fluid identification as an indicator of
      major intra-abdominal disorders must be viewed with caution and with careful
      clinical correlation.

PMID- 23011616
TI  - Sonographic features of triple-negative and non-triple-negative breast cancer.
AB  - OBJECTIVES: Triple-negative breast cancer (TNBC) is known to have unique
      molecular, clinical, and pathologic characteristics. The growth pattern of this
      cancer may also affect its appearance on sonography. Our study evaluated the
      sonographic features of TNBC according to the American College of Radiology
      Breast Imaging Reporting and Data System sonographic classification system and
      compared these features with those of non-TNBC. METHODS: Data from 315
      consecutive breast cancer cases were collected. The images were reevaluated by an
      examiner blinded to the patients' characteristics and histologic results
      according to the Breast Imaging Reporting and Data System. The sonographic
      features of TNBC (n = 33) and non-TNBC (n = 282) were compared. RESULTS: Triple
      negative breast cancer was significantly correlated with a younger patient age (P
      = .002) and was associated with higher tumor grades (P < .001), more lymph node
      involvement (P = .014), and a trend toward a larger tumor size. With regard to
      sonographic features, the margin of TNBC was more frequently described as
      lobulated or microlobulated (75.8% versus 49.5% in non-TNBC; P = .005). The
      echoic halo was observed significantly less often in TNBC than in non-TNBC(39.4%
      versus 62.8%; P = .014). Cooper ligaments were displaced rather than disrupted in
      TNBC compared to non-TNBC (P = .003). Regarding the posterior acoustic features,
      enhancement was observed significantly more often in TNBC (36.4% versus 13.0% in
      non-TNBC; P = .031). CONCLUSIONS: Triple-negative breast cancer and non-TNBC have
      different sonographic features. This finding can be explained by the pathologic
      profile of this breast cancer subtype. Some of the distinct sonographic criteria
      for TNBC are more likely to be associated with benign masses. Knowledge of the
      distinct sonographic features of TNBC would help the examiner avoid false
      negative classification of this tumor type.

PMID- 23011617
TI  - Molecular ultrasound imaging using a targeted contrast agent for assessing early
      tumor response to antiangiogenic therapy.
AB  - OBJECTIVES: Contrast-enhanced ultrasound (US) and targeted microbubbles have been
      shown to be advantageous for angiogenesis evaluation and disease staging in
      cancer. This study explored molecular US imaging of a multitargeted microbubble
      for assessing the early tumor response to antiangiogenic therapy. METHODS: Target
      receptor expression of 2LMP breast cancer cells was quantified by flow cytometric
      analysis and characterization established with antibodies against mouse
      alpha(V)beta3- integrin, P-selectin, and vascular endothelial growth factor
      receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US
      imaging of multitargeted microbubbles. Microbubble accumulation was calculated by
      destruction-replenishment techniques and time-intensity curve analysis. On day 0,
      mice underwent baseline imaging. Next, therapy group mice were injected with a
      0.2-mg dose of bevacizumab, and controls received matched saline injections.
      Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the
      mice were euthanized and tumors excised. Histologic analysis of microvessel
      density and intratumoral necrosis was completed on tumor sections. RESULTS: On
      day 3 after bevacizumab dosing, a 71.8% change in tumor vasculature was shown
      between the therapy and control groups (P = .01). The therapy group had a 15.4%
      decrease in tumor vascularity, whereas the control group had a 56.4% increase.
      CONCLUSIONS: Molecular US imaging of angiogenic markers can detect the early
      tumor response to drug therapy.

PMID- 23011618
TI  - Evaluation of subtle myocardial noncompaction by contrast echocardiography in
      patients with hypertrophic cardiomyopathy and its relationship with regional
      ventricular systolic dysfunction.
AB  - OBJECTIVES: Ourstudy was undertaken to analyze the impact of subtle noncompaction
      of the left ventricle on regional left ventricular function in patients with
      hypertrophic cardiomyopathy. METHODS: Speckle-tracking imaging and contrast
      echocardiography were performed in 40 patients with hypertrophic cardiomyopathy.
      Subtle noncompaction of the left ventricle was defined as myocardium with more
      than 3 trabeculations in a single imaging plane with a noncompaction to
      compaction ratio of greater than 0.4 and less than 2.0. RESULTS: Among 647
      segments, noncompaction was present in 46 segments (7%) in the left ventricular
      apex in 18 patients (45%) on the standard 2-dimensional echocardiograms and in
      181 segments (27%) in 32 patients (80%) on the contrast-enhanced images. The mean
      number of segments affected by noncompaction +/- SD was 6 +/- 2. The mean
      noncompacted thickness was 5.6 +/- 0.2 mm, and the ratio of the noncompacted to
      compacted layers was 1.1 +/- 0.4 on the contrast-enhanced images. The global peak
      systolic longitudinal strain in patients with hypertrophic cardiomyopathy with
      noncompaction (-12.8% +/- 2.8%) had a significantly lower absolute value than
      that in patients with hypertrophic cardiomyopathy without noncompaction (-17.4%
      +/- 1.5%; P < .05) and healthy control participants (-20.6% +/- 1.3%; P < .05).
      The number of segments with noncompaction and the interventricular septal
      thickness were both independent predictors of the global peak systolic
      longitudinal strain. CONCLUSIONS: Contrast echocardiography is superior to
      standard 2-dimensional echocardiography for detecting subtle noncompaction in
      patients with hypertrophic cardiomyopathy. We found that the global peak systolic
      longitudinal strain in patients with hypertrophic cardiomyopathy with
      noncompaction had a significantly lower absolute value than that in patients
      without noncompaction and healthy controls, indicating that the total number of
      segments affected by coexistent subtle noncompaction in patients with
      hypertrophic cardiomyopathy was an independent predictor of left ventricular
      systolic dysfunction.

PMID- 23011619
TI  - Antegrade internal carotid artery collateral flow and cerebral blood flow in
      patients with common carotid artery occlusion.
AB  - OBJECTIVES: To determine the incidence of antegrade internal carotid artery
      collateral flow in patients with common carotid artery occlusion, which artery
      supplies blood to the internal carotid artery, and whether the flow affects
      regional cerebral blood flow in the middle cerebral artery territory. METHODS: We
      determined the incidence of antegrade internal carotid artery collateral flow and
      identified its arterial origins using carotid sonography in 10 patients with
      common carotid artery occlusion and evaluated middle cerebral artery territory
      regional cerebral blood flow by single-photon emission computed tomography in
      these patients and 30 age- and sex-matched patients with internal carotid artery
      occlusion. RESULTS: Six (60%) of the 10 patients with common carotid artery
      occlusion had antegrade internal carotid artery collateral flow, which was
      supplied through the carotid bifurcation from retrograde flow of the external
      carotid artery in 5 and by a small artery directly into the internal carotid
      artery in 1. The regional cerebral blood flow ipsilateral to the occlusion at
      rest was higher in patients with common carotid artery occlusion than those with
      internal carotid artery occlusion (mean +/- SD, 40.4 +/- 8.5 versus 34.3 +/- 6.2
      mL/100 g/min; P = .02). The regional cerebral blood flow was significantly higher
      in the 6 patients with antegrade internal carotid artery flow than those with
      internal carotid artery occlusion at rest (42.2 +/- 7.2 versus 34.3 +/- 6.2
      mL/100 g/min; P = .02) but not in the other 4 patients without antegrade internal
      carotid artery flow. CONCLUSIONS: Antegrade collateral internal carotid artery
      flow was found in 60% of patients with common carotid artery occlusion and was
      mainly supplied by retrograde external carotid artery flow. It contributes to
      maintenance of middle cerebral artery territory regional cerebral blood flow.

PMID- 23011620
TI  - Characterization of carotid plaques on 3-dimensional ultrasound imaging by
      registration with multicontrast magnetic resonance imaging.
AB  - OBJECTIVES: The ability of magnetic resonance imaging (MRI) in carotid plaque
      component identification has been well established. However, compared to the
      costly nature of MRI, 3-dimensional (3D) ultrasound imaging is a more cost
      effective assessment tool. Thus, an attractive alternative for carotid disease
      monitoring would be to establish a strategy in which 3D ultrasound imaging is
      used as a screening tool that precedes MRI. To develop and validate such a
      protocol, registration between ultrasound and MR images is required. This article
      introduces a surface-based algorithm for efficient ultrasound imaging-MRI
      registration. METHODS: A surface-based 3D iterative closest point registration
      method was developed to align surfaces reconstructed from outer wall boundaries
      segmented from 3D ultrasound and MR images. The 3D ultrasound image was
      transformed according to the registration result and resliced to match
      corresponding 2-dimensional transverse MR images. Although rigid iterative
      closest point registration was used, the cross-sectional ultrasound images
      produced by the reslicing procedure can be moved relative to the MR images by an
      expert observer using in-house software, making nonrigid registration possible.
      RESULTS: We evaluated the registration accuracy associated with the algorithm
      using a vascular phantom as well as in vivo ultrasound and MR images. Our
      registration method was shown to have an average error of 0.3 mm in the phantom
      study and less than 1 mm in the in vivo study. Our findings in terms of the
      average intensity of each component are consistent with histologically validated
      results described in previous ultrasound characterization studies. CONCLUSIONS:
      We have developed a surface-based algorithm capable of registering ultrasound and
      MR images with high accuracy. This registration tool will potentially play an
      important role in a cost-effective screening protocol in which ultrasound is used
      to identify patients with a suspicion of vulnerable plaques, who are then further
      studied with MRI.

PMID- 23011621
TI  - Ultrasound measurement of brachial artery elasticity prior to hemodialysis access
      placement: a pilot study.
AB  - OBJECTIVES: Successful hemodialysis requires reliable vascular access that can
      deliver adequate blood flow. An arteriovenous fistula is preferred for access
      because of its longevity and low frequency of complications, but up to 60% of
      arteriovenous fistulas created surgically are never suitable for hemodialysis
      because of nonmaturation (insufficient vascular dilatation). Decreased arterial
      elasticity may impair dilatation, thereby affecting fistula maturation. This
      study evaluated the feasibility of brachial artery elasticity measurement in
      patients with chronic kidney disease obtained during routine pre-operative
      mapping ultrasound (US) imaging before hemodialysis access placement and compared
      the measurements to those obtained in healthy volunteers. METHODS: Brachial
      artery functional US studies were collected from 75 patients undergoing routine
      preoperative mapping for hemodialysis access and 50 healthy volunteers. Vascular
      strain was calculated from the change in intima-media thickness between end
      systole and end diastole, and vascular stress was estimated from the pulse
      pressure. Assuming a linear elastic medium, the elastic modulus was estimated as
      the ratio of vascular stress to strain. RESULTS: Elastic modulus measurements
      were significantly higher in patients than in volunteers (130 versus 100 kPa; P =
      .01). With combined volunteer and patient data, there was a significant
      correlation between elasticity and systolic blood pressure (R2 = 0.23; P < .001).
      Elasticity was correlated with age in volunteers but not in patients (R2 = 0.14;
      P = .017; R2 < .001; P = .829, respectively). CONCLUSIONS: This analysis of
      clinical arterial vessel biomechanics shows that a noninvasive US measurement can
      detect elastic modulus differences between patients with chronic kidney disease
      and healthy individuals. Future studies will correlate the elastic modulus with
      histologic characteristics and eventual arteriovenous fistula maturation, which
      may provide supplemental information on arterial biomechanical properties as a
      useful addition to current predictors of fistula success.

PMID- 23011622
TI  - Sonographic appearances of soft tissue angioleiomyomas: differences from other
      circumscribed soft tissue hypervascular tumors.
AB  - OBJECTIVES: The purpose of this study was to evaluate the sonographic features of
      angioleiomyomas with priority given to the vascular pattern to help in the
      differential diagnosis from other hypervascular soft tissue tumors. METHODS: The
      inclusion criteria for this retrospective and nonblinded study were fulfilled in
      33 patients with circumscribed hypervascular soft tissue tumors based on
      pathologic identification. Thirteen cases were angioleiomyomas; 9 cases were
      nonsubungual glomus tumors; and 11 cases were hemangiomas. Two musculoskeletal
      radiologists interpreted the results by consensus. Sonographic findings,
      including the shape, size, echogenicity, vascular pattern, and vascular density
      of the angioleiomyomas, were compared with those of the other hypervascular
      tumors. Vascular patterns were categorized into 3 vascular types: 1, several
      linear vessels clustered in the tumor with convergence to one point; 2, diffusely
      scattered irregular vessels in the tumor, and 3, one or more vessels that were
      centrally located. The vascularity of the mass was also categorized as rich
      (covering >50% of the area of the lesion), moderate (between 20% and 50%), and
      little (<20%). RESULTS: All of the angioleiomyomas were hypoechoic (100% [13 of
      13]), a statistically significant result (P = .001). The type 1 vascular pattern
      was observed in 69% of the angioleiomyomas (9 of 13; P = .029), and the
      statistically significant shape was round (38% [5 of 13]; P = .035). CONCLUSIONS:
      Most angioleiomyomas reveal a homogeneously hypoechoic echo texture with a
      circumscribed margin and show straight and linear vessels in the tumor with
      convergence to one point on color Doppler sonography. These characteristics may
      be helpful when differentiating angioleiomyomas from other circumscribed
      hypervascular soft tissue tumors.

PMID- 23011623
TI  - Sonographically guided obturator internus injections: techniques and validation.
AB  - OBJECTIVES: The primary purpose of this investigation was to describe and
      validate sonographically guided techniques for injecting the obturator internus
      (OI) muscle or bursa using a cadaveric model. METHODS: A single experienced
      operator completed 10 sonographically guided OI injections in 5 unembalmed
      cadaveric pelvis specimens (4 female and 1 male, ages 71-89 years with body mass
      indices of 15.5-24.2 kg/m2). Four different techniques were used: (1) OI tendon
      sheath (4 injections), (2) OI intramuscular (2 injections), (3) OI bursa trans
      tendinous (2 injections), and (4) OI bursa short-axis (2 injections). In each
      case, the operator injected 1.5 mL of diluted yellow latex using direct
      sonographic guidance and a 22-gauge, 87.5-mm (31/2-in) needle. Seventy-two hours
      later, study coinvestigators dissected each specimen to assess injectate
      placement. RESULTS: All 10 OI region injections accurately placed latex into the
      primary target site. Two of the 4 OI tendon sheath injections produced overflow
      into the underlying OI bursa. Both OI intramuscular injections delivered 100% of
      the latex within the OI. All 4 OI bursa injections (2 trans-tendinous and 2 short
      axis) delivered 100% of the latex into the OI bursa, with the exception that 1 OI
      bursa trans-tendinous injection produced minimal overflow into the OI itself. No
      injection resulted in injury to the sciatic nerve or gluteal arteries, and no
      injectate overflow occurred outside the confines of the OI or its bursa.
      CONCLUSIONS: The results of this investigation demonstrate that sonographically
      guided injections into the OI or its bursa are feasible and, therefore, may play
      a role in the diagnosis and management of patients presenting with gluteal and
      "retrotrochanteric" pain syndromes.

PMID- 23011624
TI  - Early detection of cardiac dysfunction by strain and strain rate imaging in
      children and young adults with marfan syndrome.
AB  - OBJECTIVES: Strain and strain rate imaging have been reported to detect cardiac
      dysfunction more accurately than conventional methods in adults with Marfan
      syndrome, but their utility has not been proven in younger patients. We sought to
      determine whether strain and strain rate imaging would allow early detection of
      cardiac dysfunction in children and young adults with Marfan syndrome. METHODS:
      Unoperated patients (<30 years) with Marfan syndrome and healthy control
      participants were prospectively enrolled. Patients with greater than mild mitral
      or aortic insufficiency were excluded. Left ventricular systolic function was
      assessed by standard M-mode imaging. The strain and strain rate values were
      obtained from apical 4-chamber (longitudinal) and parasternal short-axis views at
      basal and midventricular levels (radial and circumferential). Data from the two
      groups were compared by a t test. RESULTS: Sixteen patients with Marfan syndrome
      (mean age +/- SD, 14.4 +/- 6.4 years; range, 5.8-28.9 years) and 26 controls
      (mean age, 12.4 + 4.4 year; range, 4.1-18.1 years) were enrolled. Demographics
      and left ventricular end-diastolic dimensions were similar between the patients
      with Marfan syndrome and the controls. The M-mode-derived shortening fraction was
      significantly lower in the patients with Marfan syndrome compared to the
      controls, even though the values were within normal limits. The patients with
      Marfan syndrome had lower regional radial and circumferential strain rates, but
      there were no significant difference in strain between the groups. CONCLUSIONS:
      Strain rate imaging may be useful in detection of subclinical changes in cardiac
      function in patients with Marfan syndrome when conventional echocardiographic
      parameters are within normal limits. These findings may be clinically important
      and warrant closer follow-up of these patients to monitor for cardiac
      dysfunction.

PMID- 23011625
TI  - Prospective evaluation of Doppler sonography to detect the twinkling artifact
      versus unenhanced computed tomography for identifying urinary tract calculi.
AB  - OBJECTIVES: The twinkling artifact is an emerging tool for identifying urinary
      tract calculi. The purpose of this prospective study was to evaluate the
      diagnostic accuracy of the twinkling artifact compared to unenhanced computed
      tomography in detecting urolithasis. METHODS: After Research Ethics Board
      approval, 51 patients with flank pain from the emergency department were enrolled
      between November 2009 and September 2010. Patients received an unenhanced
      computed tomographic scan with 1.25-mm raw data and reformatted 5-mm axial and 2
      mm coronal images. Blinded assessment of the urinary tract was performed with
      gray-scale and color Doppler interrogation. The number of calculi, location,
      size, kidney distance from the skin, body mass index of the patient, and
      sonographic image parameters were recorded. RESULTS: There were 35 right-sided
      and 38 left-sided renal calculi, 14 right-sided and 21 left-sided ureteric
      calculi, and 6 bladder calculi (total, 114 calculi). Thirteen patients had no
      calculi. The average calculus size was 2.6 mm (range, 1-9 mm). There were 6 false
      positive and 22 false-negative instances of twinkling artifacts. On gray-scale
      evaluation looking for an echogenic focus with shadowing, there were 8 false
      positive and 40 false-negative findings. The positive predictive value (PPV) of
      the twinkling artifact for identifying calculi was 94%, and the sensitivity was
      83%. The PPV of gray-scale sonographic shadowing was only 64.9%, and the
      sensitivity was 80.2%. CONCLUSIONS: The twinkling artifact has a high PPV for
      detecting renal and urinary tract calculi. Evaluation for the twinkling artifact
      is a complementary technique to standard gray-scale shadowing of calculi and
      improves detection of urolithiasis on sonography.

PMID- 23011626
TI  - Clinical effectiveness of multiple-drug injection treatment in unruptured ectopic
      pregnancies: a retrospective study.
AB  - OBJECTIVES: To study the effect of local interventional treatment of unruptured
      ectopic pregnancies with multiple-drug injection guided by color Doppler
      sonography. METHODS: In this retrospective analysis, 49 patients with an
      unruptured ectopic pregnancy were treated with two different local injection
      methods administered under sonographic guidance. The patients were divided into
      single-drug (n = 23) and multiple-drug (n = 26) injection groups, and they
      received a locally administered injection of methotrexate alone or a combination
      including methotrexate, hemocoagulase, antibiotics, and anti-inflammatory drugs,
      respectively. Overall, local injection treatment was successful in 44 patients.
      The 5 patients with failed treatment underwent laparotomy about 1 week after
      single-drug injection. Serum beta-human chorionic gonadotropin (beta-hCG )
      levels, ectopic pregnancy mass sizes, blood flow at various points after
      treatment, the incidence of pelvic bleeding, and the time for serum beta-hCG
      levels to return to normal and the mass to resolve were analyzed in the remaining
      44 patients. RESULTS: Single-drug treatment was successful in 18 patients; 10 of
      23 had low to moderate pelvic bleeding after treatment, and 5 were referred for
      surgery. All 26 patients were successfully treated by multiple-drug injection.
      Only 2 patients had a small amount of pelvic bleeding. Differences between groups
      were statistically significant (P < .05) for surgery rates, the incidence of
      pelvic bleeding, transient increases in serum beta-hCG levels, mean days to
      normal beta-hCG levels, mean days of mass resolution, and mean mass diameters 1
      to 6 weeks after treatment. CONCLUSIONS: Local multiple-drug injection under
      color Doppler guidance is a new, safe, and effective method for treating
      unruptured ectopic pregnancies. It accelerates the serum beta-hCG decline and
      facilitates mass resolution. This regimen is associated with a very low rate of
      pelvic bleeding, improves the success rate of conservative treatment, and,
      therefore, has value as an important clinical application.

PMID- 23011627
TI  - Number of antral follicles, ovarian volume, and vascular indices in asymptomatic
      women 20 to 39 years old as assessed by 3-dimensional sonography: a prospective
      cross-sectional study.
AB  - OBJECTIVES: Our aim was to elicit data representative of normal findings on 3
      dimensional (3D) transvaginal gray-scale and power Doppler sonography of ovaries
      in women of fertile age. METHODS: A total of 303 gynecologically asymptomatic
      white women 20 to 39 years old with spontaneous regular menstrual cycles were
      examined with transvaginal 3D gray-scale and power Doppler sonography on cycle
      days 4 to 8. We used a 6- to 12-MHz transducer. The ovarian volume, number and
      volume of antral follicles of 2 mm or larger, vascularization index, flow index,
      and vascularization-flow index were calculated using dedicated software. Results
      are presented separately for women with follicles of 2.0 to 10.0 mm and for those
      with at least 1 follicle larger than 10.0 mm for 3 age groups: 20 to 29, 30 to
      34, and 35 to 39 years. RESULTS: There were 214 women (71%) with follicles of 2.0
      to 10.0 mm and 89 (29%) with follicles larger than 10.0 mm. In women with
      follicles of 2.0 to 10.0 mm, the right ovary was on average 0.8 cm3 larger and
      contained on average 1.2 more follicles than the left one. The ovarian volume,
      number of follicles, and total follicular volume decreased significantly with age
      in both ovaries (P = .000-.029): for the right ovary ovarian volume, the median
      (range) decreased from 8.4 (3.7-17.3) cm3 at 20 to 29 years to 6.5 (2.4-12.7)
      cm(3) at 35 to 39 years, the number of follicles from 14 (1-32) at 20 to 29 years
      to 8 (1-21) at 35 to 39 years, and the total follicular volume from 1.08 (0.01
      3.10) cm3 at 20 to 29 years to 0.84 (0.03-2.00) cm3 at 35 to 39 years. The size
      of the largest follicle and the vascular indices manifested no clear changes with
      age in any ovary. In women with follicles larger than 10 mm, the number of
      follicles decreased with age in both ovaries. CONCLUSIONS: We have elicited data
      representative of normal findings on 3D trans-vaginal sonography of ovaries in
      gynecologically asymptomatic white women of fertile age. Our gray-scale
      sonographic results may be used as reference values for general gynecology in
      populations similar to ours. Vascular indices must be interpreted with caution
      because of difficulties with standardization.

PMID- 23011628
TI  - Four-dimensional sonography with spatiotemporal image correlation and tomographic
      ultrasound imaging in the prenatal diagnosis of anomalous pulmonary venous
      connections.
AB  - OBJECTIVES: To determine whether the use of 4-dimensional (4D) sonography with
      spatiotemporal image correlation (STIC) and tomographic ultrasound imaging (TUI)
      can provide additional information with respect to 2-dimensional (2D)
      echocardiography in the prenatal diagnosis of anomalous pulmonary venous
      connections. METHODS: The study population consisted of 10 cases that were
      initially suspected to have total or partial anomalous pulmonary venous
      connections by prenatal 2D echocardiography between January 2008 and April 2011.
      All 10 cases were further examined and analyzed by 4D sonography with STIC-TUI.
      Detailed postnatal surgery or autopsy was performed on all 10 fetuses. RESULTS:
      Total anomalous pulmonary venous connections were found in 5 cases, and a partial
      connection was diagnosed in 1 fetus postnatally. The remaining 4 cases were
      confirmed to have normal pulmonary venous connections. Four of the 5 fetuses with
      anomalous pulmonary venous connections had an additional major cardiac defect; 1
      fetus had an isolated connection. Anomalous drainage was supracardiac to the
      superior vena cava in 2 cases, cardiac to the coronary sinus in 3, and partially
      infracardiac to the portal vein in remaining case. The pulmonary venous
      connections were completely and correctly visualized with 2D echocardiography in
      2 of the 10 cases, partially identified in 4, and not distinguished completely in
      4. Four-dimensional sonography imaging with STIC-TUI clearly visualized the
      connections in 9 of the 10 cases, and the remaining case was partially
      identified. CONCLUSIONS: Four-dimensional sonography with STIC-TUI facilitates
      visualization of pulmonary venous connections, thus supplying additional
      information with respect to 2D echocardiography in the prenatal diagnosis of
      anomalous pulmonary venous connections.

PMID- 23011629
TI  - Ophthalmic artery Doppler velocimetric values in pregnant women at risk for
      preeclampsia.
AB  - OBJECTIVES: The purposes of this study were to describe ophthalmic artery Doppler
      parameters in pregnant women at risk for preeclampsia in the second trimester,
      compare them with reference values described in women with healthy pregnancies,
      and evaluate the association between gestational age and Doppler parameters.
      METHODS: We conducted an observational study with prospective data collection in
      which measurements of 7 ophthalmic artery Doppler parameters were obtained in 274
      women at 20 to 28 weeks' gestation with clinical risk factors for preeclampsia.
      The following measurements were obtained: peak systolic velocity, mesodiastolic
      velocity, mean velocity, end-diastolic velocity, resistive index, pulsatility
      index, and peak ratio. The observed Doppler values were compared with reference
      values by a 1-sample t test. To test for linear associations between gestational
      age and Doppler parameters, the Pearson correlation coefficient was used.
      RESULTS: Significantly higher ophthalmic artery Doppler velocimetric parameters
      were observed when compared with the reference values. The mean values of these
      parameters +/- SD were as follows: peak systolic velocity, 37.9 +/- 10.3 cm/s
      (reference, 34.2 cm/s; P < .001); end-diastolic velocity, 7.2 +/- 3.1 cm/s
      (reference, 6.8 cm/s; P = .03); resistive index, 0.81 +/- 0.07 (reference, 0.70;
      P < .001); pulsatility index, 2.17 +/- 0.53 (reference, 1.80; P < .001); and peak
      ratio, 0.53 +/- 0.12 (reference, 0.40; P < .001). There was no correlation
      between the Doppler parameters and gestational age. CONCLUSIONS: Ophthalmic
      Doppler parameters of women at risk for preeclampsia are significantly higher
      than reference values for healthy pregnancies, which may indicate an inadequate
      vascular response to persistent peripheral resistance. Gestational age during the
      second trimester is not associated with ophthalmic artery Doppler parameters in
      pregnant women at risk for preeclampsia.

PMID- 23011630
TI  - The grand unifying theory of bright echoes in the fetal and neonatal brain.
AB  - The purpose of this presentation is to illustrate that the high-amplitude
      reflecting structures in the fetal and neonatal brain can be explained by the
      echogenicity of their leptomeningeal coverings or leptomeningeal origins. The
      leptomeninges, especially the pia mater, constitute the "grand unifying theory of
      bright reflectors" in the fetal and neonatal brain. Images from fetal and
      neonatal sonograms were selected to illustrate the objectives above.

PMID- 23011631
TI  - Prenatal visualization of the pituitary gland using 2- and 3-dimensional
      sonography: comparison to prenatal magnetic resonance imaging.
AB  - The pituitary gland is crucially important in the function of the endocrine axis.
      So far, antenatal depiction of the pituitary gland was possible only using
      magnetic resonance imaging. We describe antenatal visualization of the pituitary
      gland using 2- and 3-dimensional sonography. The appearance of the gland on
      sonography seems to be superior compares to prenatal magnetic resonance imaging.
      In cases with midline anomalies of the brain, face, or cranium, depiction of the
      pituitary gland is feasible and recommended.

PMID- 23011632
TI  - Color M-mode sonography for evaluation of fetal arrhythmias.
AB  - Fetal arrhythmias can be challenging to diagnose, even with the use of 2
      dimensional, M-mode, and spectral Doppler sonography of myocardial or blood flow
      signals to determine the rate, synchrony, and timing. Color Doppler sonography
      combined with M-mode echocardiography uses the myocardium and blood flow to
      provide a robust evaluation of cardiac rhythm. Limited descriptions of color M
      mode sonography have been published. This article describes the systematic
      application of the color M-mode technique using 4 specific clinical case examples
      and contrasts this technique with more conventional approaches to fetal
      arrhythmia diagnosis.

PMID- 23011633
TI  - Sonographic diagnosis of multiple cardiovascular malformations in a fetus with an
      interstitial 8p23.1 deletion.

PMID- 23011635
TI  - The first structural and spectroscopic study of a paramagnetic 5f DO3A complex.
AB  - A 5f(2) uranium(IV) complex of the macrocycle DO3A (DO3A = [4,7,10-tris
      carboxymethyl-,1,4,7,10-tetraaza-cyclododec-1-yl]-acetic acid) has been prepared
      and characterised in the solid state and in solution. The DO3A scaffold
      containing no strongly absorbing chromophores enables the facile detection of
      relatively long-lived (8-13 ns) UV-visible emission that possesses significant
      charge transfer character tentatively assigned to deactivation of the excited
      (3)F(2) 5f(1) 6d(1) electronic configuration. This study demonstrates, for the
      first time, that luminescence of simple U(iv) chelates is detectable in the
      absence of an antenna, potentially serving as a diagnostic tract for
      environmental U(IV) species.

PMID- 23011634
TI  - An inactivated Pseudomonas aeruginosa medicament inhibits airway allergic
      inflammation and improves epithelial functions.
AB  - The features of asthma are airway hyperresponsiveness (AHR), excess production of
      Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the
      antiasthmatic potential of an inactivated Pseudomonas aeruginosa medicament
      (PPA), as well as the underlying mechanism involved, we studied the effects of
      PPA on airway and epithelial functions. Airway resistance, cell enumeration, and
      IL-4, IFN-gamma, and IL-17 secretion in bronchoalveolar lavage fluid were assayed
      on an OVA-sensitized AHR animal model. Flow cytometry was used to observe the
      effects of PPA on cell proliferation, real-time PCR was used to test the
      expressions of toll like receptor 4 and 5, and Th17 signal molecules Act1, NF-kB
      negative regulator A20, and western blot were used to detect NF-kB expression on
      cultured human bronchial epithelial cells (BECs). PPA-treated animals had
      suppressed airway resistance, eosinophil and lymphocytes infiltration, and IL-4
      and IL-17 secretion. PPA can stimulate toll-like receptor-4 and 5 expressions,
      promote cell proliferation in normal and OVA-treated BECs, significantly decrease
      Act1 and NF-kB, and increase A20 expression in BECs treated by OVA. Our data
      suggest the therapeutic mechanism by which PPA effectively treats allergic
      inflammation on reductions of airway responsiveness, eosinophil infiltration, IL
      4 and IL-17 secretion, and improvements of epithelial functions.

PMID- 23011636
TI  - Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage
      by upregulating the DNA repair system.
AB  - Oxidative stress caused by reactive oxygen species (ROS) induces DNA base
      modifications and DNA strand breaks. In this study, the protective effect of
      baicalein against H(2)O(2)-induced DNA damage was investigated in V79-4 Chinese
      hamster fibroblast cells. H(2)O(2) treatment increased the levels of
      intracellular ROS and DNA double-strand breaks (DSBs) and decreased the level of
      Ku70 protein and the phosphorylation (activation) of DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs), which are involved in the repair of DSBs by
      nonhomologous end joining. Baicalein effectively scavenged intracellular ROS
      induced by H(2)O(2), reduced DSBs, and rescued Ku70 protein level and
      phosphorylation of DNA-PKcs. In cellular response to DNA base damage, 8
      oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in the removal of 8
      oxoguanine (8-OxoG), which is formed mainly by oxidative stress. Baicalein
      significantly decreased the levels of 8-OxoG induced by H(2)O(2), and this
      correlated with increases in OGG1 promoter activity and OGG1 mRNA and protein
      expression. The phosphorylated form of Akt kinase, which is a regulator of OGG1,
      was sharply decreased by H(2)O(2), but was prevented by baicalein. A specific Akt
      inhibitor abolished the cytoprotective effects of baicalein, suggesting that OGG1
      induction by baicalein involves the Akt pathway. In conclusion, baicalein exerted
      protective effects against DNA damage induced by oxidative stress by activating
      DNA repair systems and scavenging ROS.

PMID- 23011637
TI  - The histone methyltransferase Wolf-Hirschhorn syndrome candidate 1-like 1
      (WHSC1L1) is involved in human carcinogenesis.
AB  - Histone lysine methylation plays a fundamental role in chromatin organization.
      Although a set of histone methyltransferases have been identified and
      biochemically characterized, the pathological roles of their dysfunction in human
      cancers are still not well understood. In this study, we demonstrate important
      roles of WHSC1L1 in human carcinogenesis. Expression levels of WHSC1L1 transcript
      were significantly elevated in various human cancers including bladder carcinoma.
      Immunohistochemical analysis of bladder, lung, and liver cancers confirmed
      overexpression of WHSC1L1. WHSC1L1-specific small interfering RNAs significantly
      knocked down its expression and resulted in suppression of proliferation of
      bladder and lung cancer cell lines. WHSC1L1 knockdown induced cell cycle arrest
      at the G(2)/M phase followed by multinucleation of cancer cells. Expression
      profile analysis using Affymetrix GeneChip((r)) showed that WHSC1L1 affected the
      expression of a number of genes including CCNG1 and NEK7, which are known to play
      crucial roles in the cell cycle progression at mitosis. As WHSC1L1 expression is
      significantly low in various normal tissues including vital organs, WHSC1L1 could
      be a good candidate molecule for development of novel treatment for various types
      of cancer.

PMID- 23011639
TI  - Catalytic selective synthesis.
AB  - Complete control of the product of a catalytic reaction can be achieved on the
      basis of catalyst structure, even when the reaction conditions are nearly
      identical. Catalyst-controlled selectivity is well established for
      enantioselective catalysis but less formulated for catalytic regio-, chemo-, or
      product-selective reactions. This Review describes selective transformations of
      the same starting materials into two or more different products simply by the
      choice of catalyst. By collecting and highlighting examples of selective
      catalysis, we hope that the field will be encouraged by the progress that has
      been made while bringing attention to unmet needs in the design and mechanistic
      understanding of selective catalysts.

PMID- 23011638
TI  - Endoanal ultrasound for detection of sphincter defects following childbirth.
AB  - INTRODUCTION AND HYPOTHESIS: The objectives of this study were to estimate the
      rates of sonographically detected anal sphincter defects within 72 h of
      childbirth and to evaluate intra- and interobserver agreement using three
      dimensional (3-D) endoanal sonography data. METHODS: This is a prospective
      observational study of primiparous women delivered vaginally. Women without
      clinically identified anal sphincter lacerations underwent endoanal
      ultrasonography within 72 h of delivery. Intra- and interobserver agreement for
      diagnosis of sphincter defects using 3-D endoanal sonography data was calculated
      using kappa statistics. RESULTS: The rate of sphincter defects in 107 women
      undergoing 3-D endoanal sonography was 12 %. Characteristics of women with
      sonographically detected sphincter defects, compared to those without, included a
      significantly increased rate of clinically diagnosed second-degree lacerations
      (54 vs 20 %, p 0.008). The intra- and interobserver agreement for diagnosis of
      sphincter defects using 3-D endoanal sonography data was 0.82 [confidence
      interval (CI) 0.66-0.99] and 0.72 (CI 0.54-0.92), respectively. CONCLUSIONS: Anal
      sphincter defects detected using endoanal sonography are common, occurring in 12
      % of primiparous women, and are significantly associated with other less severe
      perineal lacerations. Overall and combining sonographically detected defects with
      clinically diagnosed lacerations, we estimate that 17.8 % of primiparous women
      delivered vaginally sustain anal sphincter injuries. The intraobserver agreement
      for diagnosis of sphincter defects is very good and the interobserver agreement
      is good.

PMID- 23011641
TI  - Using space to represent data: diagrammatic reasoning.

PMID- 23011642
TI  - Negative valence can evoke a liberal response bias in syllogistic reasoning.
AB  - Recently, studies have demonstrated that negative valence reduces the magnitude
      of the belief-bias effect in syllogistic reasoning. This effect has been
      localized in the reasoning stage, in the form of increased deliberation on trials
      where validity and conclusion believability are incongruent. Here, using signal
      detection theory, we show that the attenuation of belief bias observed when
      valence was negative can also be evoked by a liberal response bias at the
      decision stage. Indeed, when valence was negative participants adopted a more
      liberal criterion for judging syllogisms as "valid," and were overconfident in
      their judgments. They also displayed less sensitivity in distinguishing between
      valid and invalid syllogisms. Our findings dovetail with recent evidence from
      memory research suggesting that negative valence can evoke a liberal response
      bias without improving performance. Our novel contribution is the demonstration
      that the attenuating effect of negative valence on belief bias can take multiples
      routes--by influencing the decision stage as was the case here, the reasoning
      stage as has been demonstrated elsewhere, and potentially both stages.

PMID- 23011643
TI  - Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and
      proliferation of endometriotic tissues.
AB  - In order to study survivin, matrix metalloproteinases (MMP-2), membranous type 1
      matrix metalloproteinase (MT1-MMP), and tissue inhibitor metalloproteinase-2
      (TIMP-2) expression immunohistochemically in endometriotic tissues and normal
      endometrium, our retrospective study considered 194 patients affected by
      endometriosis and 71 patients with normal endometrium. Tissue microarrays were
      created from paraffin-embedded blocks; immunohistochemistry was used to assess
      protein expression. In endometriotic tissues, survivin was expressed at a higher
      level than in normal endometrium; its glandular expression level was higher in
      non-ovarian than in ovarian endometriotic tissues and lower in stromal
      components. Endometrial tissues from women without endometriosis and
      endometriotic tissues had different matrix metalloproteinase expression profiles.
      MMP-2 and MT1-MMP correlated with TIMP-2 in endometriotic tissues. Furthermore,
      in endometriotic tissues, expression of survivin, aurora B kinase, and Ki-67
      showed a significant positive correlation, which indicates a role in cellular
      proliferation that could be closely linked to its anti-apoptotic activity in
      endometriosis development. Our results imply a role for matrix metalloproteinases
      in endometriosis invasiveness; correlation of their expression with that of TIMP
      2 underscores its possible key regulatory role.

PMID- 23011644
TI  - Gastric neuroendocrine cell hyperplasia and type 1 tumours occurring within
      gastric hyperplastic polyps.
AB  - We wish to highlight the unusual occurrence of gastric neuroendocrine cell
      hyperplasia and type I neuroendocrine tumours within three hyperplastic polyps.
      In all cases, the neuroendocrine component was present within and between the
      hyperplastic foveolar glands of the polyps and overall formed the minor part of
      the polyps. Two of the patients presented with epigastric pain and the other with
      fatigue from anaemia, and on endoscopy, all three were found to have
      superficially ulcerated gastric polyps in the body (cases 1 and 2) and fundus
      (case 3). Two of the cases had serologically proven autoimmune atrophic
      gastritis, while the third case had histological evidence of an atrophic
      gastritis, most likely also autoimmune in aetiology. Cases 1 and 3 had single
      hyperplastic polyps, while case 2 had three polyps. All polyps showed linear
      neuroendocrine cell hyperplasia within hyperplastic foveolar epithelium both at
      the surface and within deeper-situated glands. Neuroendocrine
      immunohistochemistry highlighted the neuroendocrine cell hyperplasia. The bulk of
      the neuroendocrine component was restricted to hyperplastic mucosa forming the
      polyps. Non-hyperplastic adjacent mucosa showed less prominent neuroendocrine
      cell hyperplasia. It is unclear whether the two pathologies occurred
      simultaneously or independently. The common feature and causal link is atrophic
      gastritis, which predisposed the gastric mucosa to the development of both
      neuroendocrine cell hyperplasia and tumours, and hyperplastic polyps.

PMID- 23011645
TI  - Desferal as improving agent for hemoglobin fructation: structural and functional
      impacts.
AB  - Hyperglycemia and advanced glycation end products (AGEs) have considerable
      effects in diabetic patients. So, the recognition of anti-glycation property of
      compounds has a substantial benefit. Here, desferal, an iron chelator which is
      one of the most effective drugs in beta-thalassemia patients, was chosen to
      explore its effects on the fructation process of hemoglobin (Hb). The results
      indicated that desferal had a retardation effect on the functional and structural
      changes of Hb during fructation. It can prevent the AGE and carbonyl formations
      and helix depletion during the Hb fructation process. Moreover, desferal can
      preserve peroxidase and esterase activities of fructated Hb similar as native Hb.
      Therefore, desferal can be introduced as an anti-glycation drug to prevent the
      AGE formation.

PMID- 23011646
TI  - The synthesis-diffusion-degradation model explains Bicoid gradient formation in
      unfertilized eggs.
AB  - Precise formation of morphogen gradients is essential to the establishment of
      reproducible pattern in development. Mechanisms proposed for obtaining the
      requisite precision range from simple models with few parameters to more complex
      models involving many regulated quantities. The synthesis-diffusion-degradation
      (SDD) model is a relatively simple model explaining the formation of the Bicoid
      gradient in Drosophila melanogaster, in which the steady-state characteristic
      length of the gradient is determined solely by the rates of diffusion and
      degradation of the morphogen. In this work, we test the SDD model in unfertilized
      D. melanogaster eggs, which contain a single female pronucleus and lack the
      nuclear division cycles and other zygotic regulatory processes seen in fertilized
      eggs. Using two-photon live imaging as well as a novel method for quantitative
      imaging based on decorrelation of photoswitching waveforms, we find that the
      Bicoid gradient is longer and shallower in unfertilized eggs as compared to the
      gradient at the same time points in fertilized eggs. Using a means of measuring
      the Bicoid lifetime by conjugation to a photoconvertible fluorophore, we find
      that the lifetime is correspondingly longer in unfertilized eggs, providing
      qualitative and quantitative agreement with the predictions of the SDD model.

PMID- 23011647
TI  - Intrahepatic rupture of empyema gallbladder.

PMID- 23011648
TI  - Techniques for undertaking dual-energy X-ray absorptiometry whole-body scans to
      estimate body composition in tall and/or broad subjects.
AB  - Dual-energy X-ray absorptiometry (DXA) is becoming a popular tool to measure body
      composition, owing to its ease of operation and comprehensive analysis. However,
      some people, especially athletes, are taller and/or broader than the active
      scanning area of the DXA bed and must be scanned in sections. The aim of this
      study was to investigate the reliability of DXA measures of whole-body
      composition summed from 2 or 3 partial scans. Physically active young adults (15
      women, 15 men) underwent 1 whole-body and 4 partial DXA scans in a single testing
      session under standardized conditions. The partial scanning areas were head,
      whole body from the bottom of the chin down, and right and left sides of the
      body. Body-composition estimates from whole body were compared with estimates
      from summed partial scans to simulate different techniques to accommodate tall
      and/or broad subjects relative to the whole-body scan. Magnitudes of differences
      in the estimates were assessed by standardization. In simulating tall subjects,
      summation of partial scans that included the head scan overestimated whole-body
      composition by ~3 kg of lean mass and ~1 kg of fat mass, with substantial
      technical error of measurement. In simulating broad subjects, summation of right
      and left body scans produced no substantial differences in body composition than
      those of the whole-body scan. Summing partial DXA scans provides accurate body
      composition estimates for broad subjects, but other strategies are needed to
      accommodate tall subjects.

PMID- 23011653
TI  - Runners greatly underestimate sweat losses before and after a 1-hr summer run.
AB  - The purpose of this study was to determine how accurately runners estimate their
      sweat losses. Male (n = 19) and female (n = 20) runners (41 +/- 10 yr, VO2max 57
      +/- 9 ml . kg(-1) . min(-1) from the southeastern U.S. completed an ~1-hr run
      during late summer on a challenging outdoor road course (wet bulb globe
      temperature 24.1 +/- 1.5  degrees C). Runs began at ~6:45 a.m. or p.m. Before and
      after running, participants filled race-aid-station paper cups with a volume of
      fluid they felt would be equivalent to their sweat losses. Total sweat losses and
      losses by percent body weight differed (p < .01) between men (1,797 +/- 449 ml,
      2.3% +/- 0.6%) and women (1,155 +/- 258 ml, 1.9% +/- 0.4%). Postrun estimates
      (738 +/- 470 ml) were lower (p < .001) than sweat losses (1,468 +/- 484 ml),
      equaling underestimations of 50% +/- 23%, with no differences in estimation
      accuracy by percentage between genders. Runners who reported measuring changes in
      pre- and postrun weight to assess sweat losses within the previous month (n = 9, 
      54% +/- 18%) were no more accurate (p = .55) than runners who had not (n = 30, 
      48% +/- 24%). These results suggest that inadequate fluid intake during runs or
      between runs may stem from underestimations of sweat losses and that runners who
      do assess sweat-loss changes may be making sweat-loss calculation errors or do
      not accurately translate changes in body weight to physical volumes of water.

PMID- 23011654
TI  - Tyrosine supplementation does not influence the capacity to perform prolonged
      exercise in a warm environment.
AB  - Eight young men were recruited to a study designed to examine the effect of
      tyrosine (TYR) supplementation on the capacity to perform prolonged exercise in a
      warm environment. Subjects entered the laboratory in the morning and remained
      seated for 1 hr before cycling to exhaustion at 70% VO2peak. Two 250-ml aliquots
      of a placebo (PLA ) or a TYR solution were ingested at 30-min intervals before
      exercise, with an additional 150 ml consumed every 15 min throughout exercise
      (total TYR dose: 150 mg/kg BM). Cognitive function was assessed before drink
      ingestion, at the end of the rest period, and at exhaustion. TYR ingestion had no
      effect on exercise capacity (PLA 61.4 +/- 13.7 min, TYR 60.2 +/- 15.4 min; p =
      .505). No differences in heart rate (p = .380), core temperature (p = .554), or
      weighted mean skin temperature (p = .167) were apparent between trials. Ingestion
      of TYR produced a marked increase in serum TYR concentrations (+236 +/- 46
      MUmol/L; p < .001), with this difference maintained throughout exercise. No
      change was apparent during the PLA trial (p = .924). Exercise caused an increase
      in error rate during the complex component of the Stroop test (p = .034), but
      this response was not influenced by the drink ingested. No other component of
      cognitive function was altered by the protocol (all p > .05). Ingestion of a TYR
      solution did not influence time to exhaustion or several aspects of cognitive
      function when exercise was undertaken in a warm environment.

PMID- 23011655
TI  - Dietary and training predictors of stress fractures in female runners.
AB  - PURPOSE: To compare female runners with and without a history of stress fractures
      to determine possible predictors of such fractures. METHODS: 27 female runners
      (age 18-40 yr) who had had at least 1 stress fracture were matched to a control
      sample of 32 female runners without a history of stress fractures. Bone mineral
      density (BMD) was measured by dual-energy X-ray absorptiometry (iDXA). Subjects
      answered questionnaires on stress-fracture history, training, menstrual status,
      and diet. RESULTS: No significant differences were found in menstrual
      characteristics, diet and dairy intake, or bone measurements. Weekly servings of
      milk during middle school significantly predicted BMD at the femur (p = .010),
      femoral neck (p = .002), Ward's triangle (p = .014), and femoral shaft (p =
      .005). Number of menstrual cycles in the previous year predicted femoral-neck BMD
      (p = .004). Caffeine intake was negatively associated with BMD of the femur (p =
      .010), femoral neck (p = .003), trochanter (p = .038), and femoral shaft (p =
      .035). Weekly hours of training were negatively associated with total-body BMD (p
      = .021), total-body bone mineral content (p = .028), and lumbar-spine BMD (p =
      .011). Predictors for stress fractures included the number of years running,
      predominantly running on hard ground, irregular menstrual history, low total-body
      BMD, and low current dietary calcium intake when controlling for body-mass index
      (Nagelkerke R2 = .364). CONCLUSIONS: Servings of milk during middle-school years
      were positively correlated with hip BMD, although current calcium intake, low
      BMD, irregular menstrual history, hard training surface, and long history of
      training duration were the most important predictors of stress fractures.

PMID- 23011656
TI  - Relationship between eating-behavior disorders and psychological parameters in
      male first-year physical education students.
AB  - This study explores the prevalence of disordered eating attitudes in a sample of
      male first-year university students engaged in a physical education program and
      examines the relationships between emotional intelligence, coping, and emotional
      eating in relation to disordered-eating (DE) attitudes. A total of 140 students
      completed the following questionnaires: the eating attitudes test, the bar-on
      emotional intelligence questionnaire, the coping inventory stress scale, and the
      Dutch eating behavior questionnaire. The number of participants represented 80%
      of the male students registered in this discipline at the authors' university.
      Twenty percent of students presented DE attitudes even though they were of normal
      weight. The bar-on EQ-I results indicated that students with DE attitudes had
      lower levels of emotional intelligence (EI) scores than students without DE
      attitudes (control group). Moreover, they scored higher than the control group on
      coping styles such as avoidance-oriented coping, emotion-oriented coping, and
      emotional eating. The DE group presented a positive correlation between DE
      attitudes symptoms and both avoidance- and emotion-oriented coping but a negative
      correlation between DE attitudes and task-oriented coping. There was also a
      significant negative correlation between DE attitudes and EI score. Another
      result from this group indicated an association between EI score and emotional
      eating score (p < .05, r = -.44) and also a positive correlation between emotion
      oriented coping and emotional eating (p < .01, r = .47). The findings highlight
      future research potential on the role of emotions and EI in DE symptoms, which
      may be beneficial in the context of collaborative care management intervention.

PMID- 23011657
TI  - Case study: Nutrition and training periodization in three elite marathon runners.
AB  - Laboratory-based studies demonstrate that fueling (carbohydrate; CHO) and fluid
      strategies can enhance training adaptations and race-day performance in endurance
      athletes. Thus, the aim of this case study was to characterize several periodized
      training and nutrition approaches leading to individualized race-day fluid and
      fueling plans for 3 elite male marathoners. The athletes kept detailed training
      logs on training volume, pace, and subjective ratings of perceived exertion (RPE)
      for each training session over 16 wk before race day. Training impulse/load
      calculations (TRIMP; min * RPE = load [arbitrary units; AU]) and 2 central
      nutritional techniques were implemented: periodic low-CHO-availability training
      and individualized CHO- and fluid-intake assessments. Athletes averaged ~13
      training sessions per week for a total average training volume of 182 km/wk and
      peak volume of 231 km/wk. Weekly TRIMP peaked at 4,437 AU (Wk 9), with a low of
      1,887 AU (Wk 16) and an average of 3,082 +/- 646 AU. Of the 606 total training
      sessions, ~74%, 11%, and 15% were completed at an intensity in Zone 1 (very easy
      to somewhat hard), Zone 2 (at lactate threshold) and Zone 3 (very hard to
      maximal), respectively. There were 2.5 +/- 2.3 low-CHO-availability training
      bouts per week. On race day athletes consumed 61 +/- 15 g CHO in 604 +/- 156
      ml/hr (10.1% +/- 0.3% CHO solution) in the following format: ~15 g CHO in ~150 ml
      every ~15 min of racing. Their resultant marathon times were 2:11:23, 2:12:39
      (both personal bests), and 2:16:17 (a marathon debut). Taken together, these
      periodized training and nutrition approaches were successfully applied to elite
      marathoners in training and competition.

PMID- 23011659
TI  - Ultrasonography reveals nail thickening in patients with chronic plaque
      psoriasis.
AB  - Nail psoriasis is usually investigated and diagnosed by clinical examination.
      Ultrasonography is a non-invasive imaging technique for studying soft tissue
      involvement. The objective of this study was to estimate nail involvement in
      patients with chronic plaque psoriasis by ultrasonography. Prevalence, clinical
      type and severity of nail involvement according to nail psoriasis and severity
      index (NAPSI) were investigated in 138 patients with psoriasis. The thickness of
      the plate and bed of the fingernails was measured in 54 patients with psoriasis,
      46 healthy controls and 37 patients with chronic eczema, using an
      ultrasonographic system equipped with a frequency transducer of 18 MHz. The
      prevalence of nail psoriasis was 73 % (102 out of 138). Onycholysis and
      thickening of the nail plate were the most common clinical type affecting 56 and
      50 % of patients, respectively; splinter haemorrhages was the less common
      involving 10 % of patients. The mean NAPSI score was 18.4 +/- 17.5 (SD; range 0
      107). The thickness of fingernail plate and bed was significantly higher in
      patients with psoriasis with nail disease compared to healthy controls and
      patients with chronic eczema (p < 0.001). There was a linear correlation between
      NAPSI and plate and bed nail thickness (r = 0.52 and r = 0.38, p = 0.001).
      Increased nail plate and bed thickness was observed also in patients with
      psoriasis without clinically apparent nail involvement. In conclusion, thickening
      of the nail is a common feature of nail psoriasis also in patients without
      clinically apparent nail involvement.

PMID- 23011658
TI  - Oxidative stress markers are increased since early stages of infection in
      syphilitic patients.
AB  - Clinical symptoms of syphilis are the consequence of the spirochete propensity to
      induce persistent chronic inflammation, which could participate to oxidative
      stress increase. The present study was designed to evaluate the level of
      oxidative stress biomarkers and antioxidant defences in a cohort of syphilitic
      patients. Serum oxidative status was explored in 63 patients diagnosed with early
      syphilis, 34 consulting patients negative for syphilis and 19 healthy controls.
      Total plasma thioredoxin (Trx) and thiols were determined as antioxidant capacity
      markers,  degrees NO, advanced oxidation protein products (AOPP) and protein
      carbonyl levels as oxidative stress status biomarkers, and CRP as marker of
      inflammation. Mean serum levels of Trx, AOPP, carbonyls, and nitrates/nitrites
      were significantly higher, whereas thiols level was lower in syphilitic patients
      compared to non-syphilitic patients and healthy controls (respectively, p <
      0.05/p < 0.01 for Trx, p < 0.005/p < 0.0001 for AOPP, p < 0.05/p < 0.005 for
      carbonyls, p < 0.005/p < 0.05 for nitrates/nitrites and p < 0.01/p < 0.0001 for
      thiols). According to the stage of the disease, results highlighted a marked and
      sustained oxidative stress imbalance from the first stage to the latent period of
      the disease. Moreover, syphilitic patients presented a low inflammation status
      reflected by median of CRP level (1.7 mg/L, range 5th-95th percentile from <0.1
      to 33.7 mg/L), correlated with antioxidant capacity decrease (thiols) at stage 1
      (r = -0.725; p < 0.0001) and nitrosative stress increase (nitrates/nitrites) at
      stage 2 and latent (respectively, r = 0.285, p < 0.05 and r = 0.650, p < 0.05).
      These findings indicate that at all stages of the disease, despite a low-grade
      inflammatory state, syphilis infection generates a major oxidative and
      nitrosative stress which may be involved in the pathophysiology of the disease.

PMID- 23011660
TI  - Effects of Cervi cornus Colla (deer antler glue) in the reconstruction of a skin
      equivalent model.
AB  - The aim of this study was to investigate the effects of Cervi cornus Colla (CCC)
      in the reconstruction of skin equivalent (SE). H&E staining showed that SE
      containing hyaluronic acid (HA) or HA and CCC had a thicker epidermis than the
      control SE. Immunohistochemical staining showed that p63 was mainly present at
      the basal layer of the epidermis in the HA and CCC model. Involucrin was
      obviously expressed in the upper layer of the epidermis in the HA and CCC model.
      Moreover, we observed that integrins alpha6 and beta1 were strongly expressed
      along the basement membrane zone in the HA and CCC model, in which the dermis
      expressing type I collagen was more compact. In conclusion, our data indicate
      that CCC contributed to the formation of epidermis, basement membrane, and
      extracellular matrix in the reconstruction of SE and suggest that CCC may be a
      useful adjuvant in the reconstruction of SE.

PMID- 23011661
TI  - Effect of trypsin and mucin on heme iron bioavailability in humans.
AB  - In the human gastrointestinal tract, trypsin and mucin may affect the absorption
      of heme iron. However, these interactions have not been well-established. We
      determined the effect of trypsin and mucin on heme iron absorption in humans.
      DESIGN: Twenty-eight apparently healthy females participated in two studies (14
      per study). Study A evaluated the effect of trypsin on iron bioavailability.
      Subjects ingested 100 mg trypsin and 1.7 g mucin on 5 mg heme iron
      bioavailability on days 1, 2, 14, and 15, respectively. In study B, which
      assessed the effect of mucin on heme iron bioavailability, the subjects ingested
      hemin, hemin plus mucin, hemoglobin (Hb), and Hb plus mucin, on days 1, 2, 14,
      and 15, respectively. RESULTS: In study A, the geometric means +/- 1 SD of heme
      iron absorption were 5.1 % (3.1-8.3), 2.9 % (1.6-5.1), 7.3 % (4.1-13.1), and 6 %
      (2.7-13) for hemin, hemin plus trypsin, Hb plus trypsin, and Hb plus mucin plus
      trypsin, respectively. In study B, the geometric means +/- 1 SD of heme iron
      absorption were 16.4 % (10.5-25.7), 13.1 % (9.0-18.9), 13.7 % (9.0-20.7), and
      11.8 % (7.6-18.3) for hemin, hemin plus mucin, Hb, and Hb plus mucin,
      respectively. The ratio increased when Hb plus trypsin was ingested and decreased
      when hemin plus trypsin was ingested. There were no differences in other ratios
      with respect to the ratio on day 1 (P < 0.05). CONCLUSION: Trypsin is the only
      human gastrointestinal protein that evaluated the affects of heme iron
      absorption. However, this effect depends on how heme iron is ingested.

PMID- 23011662
TI  - Urinary monitoring of exposure to yttrium, scandium, and europium in male Wistar
      rats.
AB  - On the assumption that rare earth elements (REEs) are nontoxic, they are being
      utilized as replacements of toxic heavy metals in novel technological
      applications. However, REEs are not entirely innocuous, and their impact on
      health is still uncertain. In the past decade, our laboratory has studied the
      urinary excretion of REEs in male Wistar rats given chlorides of europium,
      scandium, and yttrium solutions by one-shot intraperitoneal injection or oral
      dose. The present paper describes three experiments for the suitability and
      appropriateness of a method to use urine for biological monitoring of exposure to
      these REEs. The concentrations of REEs were determined in cumulative urine
      samples taken at 0-24 h by inductively coupled plasma atomic emission
      spectroscopy, showing that the urinary excretion of REEs is <2 %. Rare earth
      elements form colloidal conjugates in the bloodstream, which make high REEs
      accumulation in the reticuloendothelial system and glomeruli and low urinary
      excretion. The high sensitivity of inductively coupled plasma-argon emission
      spectrometry analytical methods, with detection limits of <2 MUg/L, makes urine a
      comprehensive assessment tool that reflects REE exposure. The analytical method
      and animal experimental model described in this study will be of great importance
      and encourage further discussion for future studies.

PMID- 23011664
TI  - Modeling the influence of slurry concentration on Saccharomyces cerevisiae cake
      porosity and resistance during microfiltration.
AB  - Filtration of an isotonic suspension of baker's yeast through a 0.45-MUm membrane
      was studied at two different pressures, 40 and 80 kPa, for yeast concentrations
      ranging from 0.14 to 51 kg/m(3) (dry weight). For a yeast volume fraction above
      0.06 (~21.8 kg/m(3) ), the porosity of the yeast cake is less dependent on the
      suspension concentration. For highly diluted suspensions, the specific cake
      resistance approaches a minimum that depends on the filtration pressure.
      Correlation functions of cake porosity and specific cake resistance were obtained
      for the concentration range investigated showing that the Kozeny-Carman
      coefficient increases when the applied pressure increases. Both filtration
      pressure and slurry concentration can be process controlled. In the range of
      moderate yeast concentration, the filtrate flux may be increased by manipulating
      the filtration pressure and the slurry concentration, thereby improving the
      overall process efficiency. The complex behavior of yeast cakes at high slurry
      concentration can be described by a conventional model as long as part of yeast
      cells are assumed to form aggregates, which behave as single bigger particles.
      The aggregation effect may be accounted for using a binary mixture model.

PMID- 23011666
TI  - [BSG (federal social court) prohibits external collaborations in ambulatory
      surgeries].

PMID- 23011663
TI  - Comparative analysis of the protective effects of caffeic acid phenethyl ester
      (CAPE) on pulmonary contusion lung oxidative stress and serum copper and zinc
      levels in experimental rat model.
AB  - The aim of this study was to investigate the effects of caffeic acid phenethyl
      ester (CAPE) in the lungs by biochemical and histopathological analyses in an
      experimental isolated lung contusion model. Eighty-one male Sprague-Dawley rats
      were used. The animals were divided randomly into four groups: group 1 (n = 9)
      was defined as without contusion and without CAPE injection. Group 2 (n = 9) was
      defined as CAPE 10 MUmol/kg injection without lung contusion. Group 3 (n = 36)
      was defined as contusion without CAPE-administrated group which consisted of four
      subgroups that were created according to analysis between days 0, 1, 2, and 3.
      Group 4 (n = 27) was defined as CAPE 10 MUmol/kg administrated after contusion
      group divided into three subgroups according to analysis on days 1, 2, and 3.
      CAPE 10 MUmol/kg was injected intraperitoneally 30 min after trauma and on days 1
      and 2. Blood samples were obtained to measure catalase (CAT) and superoxide
      dismutase (SOD) activities and level of malondialdehyde (MDA) and for blood gas
      analysis. Trace elements such as zinc and copper were measured in serum. The lung
      tissue was also removed for histopathological examination. Isolated lung
      contusion increased serum and tissue SOD and CAT activities and MDA levels (p <
      0.05). Both serum and tissue SOD, MDA, and CAT levels on day 3 were lower in
      group 4 compared to group 3 (p < 0.05). Further, the levels of SOD, MDA, and CAT
      in group 4 were similar compared to group 1 (p > 0.05). CAPE also had a
      significant beneficial effect on blood gases (p < 0.05). Both serum zinc and
      copper levels were (p < 0.05) influenced by the administration of CAPE.
      Histopathological examination revealed lower scores in group 4 compared to group
      3 (p < 0.05) and no significant differences compared to group 1 (p > 0.05). CAPE
      appears to be effective in protecting against severe oxidative stress and tissue
      damage caused by pulmonary contusion in an experimental setting. Therefore, we
      conclude that administration of CAPE may be used for a variety of conditions
      associated with pulmonary contusion. Clinical use of CAPE may have the advantage
      of prevention of pulmonary contusion.

PMID- 23011667
TI  - [Objective audiological diagnosis].

PMID- 23011669
TI  - Effect of multiple stresses on growth and adaptive capability of Malpura ewes
      under semi-arid tropical environment.
AB  - A study was conducted to assess the effect of multiple stresses (thermal,
      nutritional, and walking stress) on the adaptive capability of Malpura ewes in
      terms of changes in physiological mechanisms and blood biochemical changes. The
      study was conducted for a period of 35 days covering two estrous cycles during
      summer season (April-May). The ewes were randomly allocated into two groups of 12
      animals each, viz., GI (n = 12; control) and GII (n = 12; multiple stresses). GI
      ewes were maintained in the shed while GII ewes were subjected to multiple
      stresses. GI ewes were maintained in shed while GII ewes were subjected to heat
      stress by exposing them to 32-44  degrees C (average 42  degrees C) and RH of 12
      26 % for 6 h from 10:00 to 16:00 h in natural environment. GI ewes were provided
      with ad libitum feeding while GII ewes were provided with restricted feed (30 %
      of intake of GI ewes) to induce nutritional stress. Further, GII ewes were
      subjected to walking stress by forcing them to walk 14 km in two spans between
      9:00 and 10:30 h and 15:00 and 16:30 h. Blood collection was done at weekly
      intervals. Multiple stresses significantly (P < 0.01) affected body weight,
      respiration rate, pulse rate, rectal temperature, sweating rate, tri-iodo
      thyronine, thyroxine, cortisol, hemoglobin, packed cell volume, glucose, and
      total protein. The findings from this experiment provide useful information to
      understand the ideal nutrient requirement for these animals to adapt to such
      stresses in the semi-arid tropical environment without compromising production.

PMID- 23011671
TI  - Production potentials of native chickens (Gallus gallus domesticus L.) of Western
      Visayas, Philippines.
AB  - Poultry genetic resources diversity serves as a reservoir of genes adaptable to
      local conditions, production, resource utilization, and production that are
      compatible with consumer preferences for meat and egg products. This study was,
      therefore, conducted to determine the production potentials of native chickens in
      Western Visayas, Philippines. A total of 270 raisers were interviewed and 810
      chickens were characterized. These numbers were divided equally among the
      provinces of Aklan, Antique, Capiz, Guimaras, Iloilo, and Negros Occidental. The
      data collected were analyzed using one-way analysis of variance and significant
      differences were determined using the Duncan's Multiple Range Test. Results show
      that native chickens from Aklan had the highest (P < 0.01) hatching percentage
      (93.10 +/- 1.67 %) and oldest (P < 0.01) slaughter/marketing age (23.56 +/- 1.03
      weeks). Those from Guimaras had the biggest (P < 0.01) egg (42.69 +/- 0.87 g) and
      heaviest slaughter/marketing weight (920.00 +/- 22.72 to 924.44 +/- 23.01 g); the
      shortest (P < 0.01) clutch interval (77.87 +/- 4.14 days) was observed from those
      in Iloilo. Those from Antique had the highest (P < 0.01) survival rate from 1 day
      old to a slaughter/marketing age of 52.48 +/- 1.83 %. The adult live weight
      ranged from 1.27 +/- 0.04 to 1.62 +/- 0.04 kg with those from Aklan as the lowest
      (P < 0.01) while those from Guimaras were the highest. Thus, the observed
      variations in reproductive and growth performances of native chickens from this
      region expressed their potentials for genetic improvement toward production.

PMID- 23011670
TI  - Salmonella enterica subsp. enterica isolated from chicken carcasses and
      environment at slaughter in Reunion Island: prevalence, genetic characterization
      and antibiotic susceptibility.
AB  - Salmonella contamination of 71 chicken broiler flocks was investigated at the
      slaughterhouse in Reunion Island between October 2007 and January 2009. Samples
      were collected from live broiler chickens and chicken carcasses as well as the
      slaughterhouse environment. Salmonella spp. was isolated from 40 of 71 (56 % with
      a confidence interval 5 % [45-67]) broiler chicken flocks at slaughter. The most
      prominent serovars were Blockley (31 %), Typhimurium and Brancaster (14 %), Hadar
      (10 %), Salmonella multidrug resistant clinical organisms serotypes 1,4,[5],12:i:
      , and Virchow (8 %) and Livingstone, St. Paul, Seftenberg, Llandoff, Infantis and
      Indiana. At the farm, 27 % of the broiler chicken flocks tested positive for
      Salmonella spp. Salmonella spp. was isolated from 124 of 497 environmental
      samples (25 %). In most cases, there was no relationship between pulsed field gel
      electrophoresis (PFGE) pattern and antibiotic resistance pattern. The predominant
      Salmonella serovars were susceptible to most of the tested antibiotic drugs, but
      S. Hadar exhibited multidrug resistance. This study highlighted the primary
      source of Salmonella was the farm of origin and downstream stages in processing
      could not remedy to but amplify this Salmonella contamination.

PMID- 23011672
TI  - Prevalence and genotypic (G and P) determination of porcine group A rotaviruses
      from different regions of India.
AB  - Group A rotaviruses can infect both humans and animals and have been recognized
      as an important cause of diarrhea in porcine. In this study, we report the
      prevalence and molecular epidemiology of rotaviruses detected in piglets in
      different regions of India. A total 275 fecal samples (180 diarrheal and 95 non
      diarrheal) from piglets were collected from the western (135), southern (60),
      northern (20), and North-Eastern Hill (NEH) (60) regions of India and tested for
      rotaviruses. All the samples were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and reverse transcription
      polymerase chain reaction (RT-PCR). Rotaviruses were detected in 10.18 % of
      samples by SDS-PAGE and/or RT-PCR with a maximum of 30 % from the NEH region
      followed by 7.4 % from the western region. Samples from the southern and northern
      regions were found to be negative. Only 10 isolates were subjected to genotypic
      characterization using amplification of VP7 and VP4 genes followed by two
      separate multiplex PCR assays for G genotyping and another two for P genotyping
      using genotype-specific primers. Of these, three isolates could be typed as G4
      specificity, one with G9, and three as P[6] leading to identification of an
      uncommon strain, G4P[6]. One isolate was further confirmed by nucleotide
      sequencing. The data demonstrate genetic diversity of porcine rotavirus strains
      and suggest that pig farms may serve as potential reservoirs for human
      infections.

PMID- 23011673
TI  - Characteristics of snail farming in Edo South Agricultural Zone of Edo State,
      Nigeria.
AB  - The study was carried out to determine the characteristics of snail farming in
      Edo South Agricultural Zone of Edo State Nigeria. The interview schedule was used
      to collect data from 60 snail farmers randomly selected from six cells in the
      study area. Information on the socioeconomic status of the farmers, production
      system, management practices and production constraints in the snail farms were
      elicited. The constraints were determined using a four-point Likert-type scale; a
      mean score of >= 2.5 was considered as a production constraint. Majority (85.0 %)
      of the respondents were part-time snail farmers. The major species of snails
      reared were Achatina achatina and Archachatina marginata, reared by 43.3 and 26.7
      % of the farmers, respectively. Semi-intensive system of production was practised
      by 40.0 % of the farmers. Majority (78.0 %) of the respondents used car tyres to
      house their snails. About 56 % of the respondents kept their snails for 1-2 years
      before sale. Up to 51.7 % of the respondents separated their snails into
      different pens according to their size/age. The most commonly used feeds were
      vegetables (71.2 %), plant leaves (67.8 %) and kitchen waste (59.3 %). Records of
      snail production activities were kept by 75.0 % of respondents. The major
      constraints identified were lack of capital (3.31), inability to get good laying
      stock (3.00), lack of formulated feed to buy (2.98) and slow growth rate of
      snails (2.52). The potentials of snail farming in the study area have not been
      fully exploited as farmers produced at subsistence level.

PMID- 23011674
TI  - Importance of occlusal plane reproduction on the semi-adjustable articulator in
      planning maxillary impactions for orthognathic surgery.
AB  - INTRODUCTION: The aim of this study was to evaluate whether a 6 degrees 
      counterclockwise change in occlusal plane inclination would produce significant
      modifications on the final result of a maxillary impaction and mandible
      advancement model surgery. MATERIALS AND METHODS: Four groups were used in this
      study, with ten identical maxillary casts and one mandibular cast mounted on the
      same semi-adjustable articulator, with the same malocclusion. The occlusal plane
      of the two control and study groups had an inclination of 13 degrees  and 7
      degrees , respectively. Preoperative and postoperative measures were performed
      using the Erickson platform and impactions of 6 and 10 mm were tested. To control
      these movements during model surgery, two splints were fabricated using another
      two maxillary and mandibular casts mounted with occlusal plane of 13 degrees ,
      simulating the proposed movement. RESULTS: The results were compared using the t
      test. Only the antero-posterior movement of the upper incisor was statistically
      significant for both study groups (p < 0.05), with a mean of 0.48 and 0.94 mm in
      the 10 and 6 mm impaction groups, respectively. DISCUSSION: This information
      means that if an error in the occlusal plane transference occur, it will not be
      clinically significant, because differences smaller than 1 mm does not have
      influence on soft and hard tissue final result.

PMID- 23011675
TI  - ERCP in the management of choledocholithiasis in pregnancy.
AB  - The physiological changes of pregnancy increase the risk of gallstone formation,
      and choledocholithiaisis is the most common indication for endoscopic retrograde
      cholangiopancreatography (ERCP) during pregnancy. ERCP has been performed during
      pregnancy for over 20 years. Despite the apparent efficacy and lack of adverse
      fetal outcomes in published case series and reports, there remains a concern for
      the use of fluoroscopy during pregnancy. Recent focus has centered around
      avoidance of the use of fluoroscopy during ERCP, including the use of alternative
      techniques to confirm biliary cannulation and ductal clearance. The benefits of
      these techniques over traditional ERCP technique are unclear. In this article, we
      will review the epidemiology of gallstone disease during pregnancy, outline the
      risks of ERCP during pregnancy, and describe recent novel techniques in
      endoscopic biliary intervention for biliary drainage and ductal clearance.

PMID- 23011676
TI  - Difficult biliary access for ERCP.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is a technically-demanding
      procedure. The ability to selectively cannulate the bile duct and pancreatic duct
      (PD) quickly and atraumatically is the key to successful therapeutic ERCP, and to
      minimizing post-ERCP complications, especially pancreatitis (PEP). Prophylactic
      stenting of the PD has significantly reduced the risk of severe PEP. Difficult
      ERCP access refers to the length of time and number of attempts it takes to
      achieve deep cannulation of the desired duct. If biliary access cannot be
      achieved quickly, PD stenting over a guide wire is recommended, which facilitates
      further attempts to enter the bile duct. Familiarity with guide wires and needle
      knife papillotomy technique are necessary to achieve close to 100 % biliary
      cannulation. Anatomic abnormalities, from gastric outlet strictures,
      periampullary diverticula, and ampullary masses to surgical rearrangement of the
      upper GI tract, contribute to the difficulty of performing ERCP. Adjunctive
      techniques to overcome these problems include percutaneous transhepatic biliary
      access and endoscopic ultrasound (EUS)-guided puncture of the bile duct through
      the stomach or duodenal wall. Therapeutic EUS is emerging as a major tool in the
      management of pancreatic and biliary disease, and will likely replace many
      therapeutic ERCP techniques in the next decade.

PMID- 23011677
TI  - Macrophage stimulating protein promotes liver metastases of small cell lung
      cancer cells by affecting the organ microenvironment.
AB  - The organ microenvironment significantly affects the processes of cancer
      metastasis. Elucidating the molecular mechanisms of interaction between tumor
      cells and the organ microenvironment is crucial for the development of effective
      therapeutic strategies to eradicate cancer metastases. Macrophage stimulating
      protein (MSP), an activator of macrophages, regulates a pleiotropic array of
      effects, including proliferation, cellular motility, invasiveness, angiogenesis,
      and resistance to anoikis. However, the role of MSP in cancer metastasis is still
      largely unknown. In this study, the action of MSP on the production of metastases
      was determined in a multiple-organ metastasis model. The murine MSP gene was
      transfected into two human SCLC cell lines, SBC-5 and H1048, to establish
      transfectants secreting biologically active MSP. MSP gene transduction did not
      affect cell proliferation and motility in vitro. Intravenously inoculated MSP
      transfectants produced significantly larger numbers of liver metastases than
      parental cells or vector control clones, while there were no significant
      differences in bone or lung metastases among them. Immunohistochemical analyses
      of liver metastases revealed that tumor-associated microvessel density and tumor
      infiltrating macrophages were significantly increased in lesions produced by MSP
      transfectants. MSP could stimulate the migration of murine macrophages and
      endothelial cells in vitro. Consequently, MSP may be one of the major
      determinants that affects the properties of tumor stroma and that produces a
      permissive microenvironment to promote cancer metastasis.

PMID- 23011678
TI  - "Hard-soft" synthesis of SrCrO3-delta superstructure phases.

PMID- 23011679
TI  - Mean retinal ganglion cell axon diameter varies with location in the human
      retina.
AB  - PURPOSE: We examined retinal ganglion cell (RGC) axon diameters within the human
      retinal nerve fibre layer in order to provide information about the possible
      effects of axonal stimulation when a retinal prosthesis includes the nonfoveal
      regions. METHODS: Five pairs of eyes were obtained from donors aged from 48 to 84
      years. Fixation delay ranged from 5 to 22 h. Tissue was processed for electron
      microscopy. RESULTS: Inferior and/or nasal RGC axons were on average larger than
      superior and/or temporal axons. The inferior retina contained some very large
      axons. Foveal axons were on average smaller than nonfoveal axons and had a size
      distribution that suggested different size groupings not seen in other samples.
      Peripheral versus central axons within the superior and inferior nasal retinal
      samples were compared; peripheral axons were significantly larger, unlike the
      inferior temporal samples or the samples nasal to the optic disc. CONCLUSIONS:
      Stimulus-current thresholds will change as a retinal prosthesis increases in size
      and encroaches on the nonfoveal axons. These changes can be anticipated based on
      mean axon diameter. Knowing in advance the possible outcome of electrical
      stimulation of the axonal population may help refine prosthetic procedures and
      patient training.

PMID- 23011680
TI  - Are changes in bone mineral density different between groups of early rheumatoid
      arthritis patients treated according to a tight control strategy with or without
      prednisone if osteoporosis prophylaxis is applied?
AB  - Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy
      does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving
      preventive treatment for osteoporosis. A small increase in lumbar bone mineral
      density (BMD) during the first year of treatment was recorded, regardless of use
      of glucocorticoids. INTRODUCTION: This study aims to describe effects on BMD of
      treatment according to EULAR guidelines with a methotrexate-based tight control
      strategy including 10 mg prednisone daily versus the same strategy without
      prednisone in early RA patients who received preventive therapy for osteoporosis.
      METHODS: Early RA patients were included in the CAMERA-II trial: a randomized,
      placebo-controlled, double-blind 2-year trial, in which effects of addition of 10
      mg prednisone daily to a methotrexate-based tight control strategy were studied.
      All patients received calcium, vitamin D and bisphosphonates. Disease activity
      was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray
      absorptiometry of lumbar spine and left hip were performed at baseline and after
      1 and 2 years of treatment. RESULTS: BMD increased significantly over time in
      both treatment groups at the lumbar spine with a mean of 2.6% during the first
      year (p<0.001), but not at the hip; at none of the time points did BMD differ
      significantly between the prednisone and placebo group. Higher age and lower
      weight at baseline and higher disease activity scores during the trial, but not
      glucocorticoid therapy, were associated with lower BMD at both the lumbar spine
      and the hip in mixed-model analyses. CONCLUSION: Addition of 10 mg prednisone
      daily to a methotrexate-based tight control strategy does not lead to bone loss
      in early RA patients on bisphosphonates. A small increase in lumbar BMD during
      the first year of treatment was found, regardless of use of glucocorticoids.

PMID- 23011681
TI  - The assessment of vertebral fractures in elderly women with recent hip fractures:
      the BREAK Study.
AB  - This study aimed to evaluate the prevalence of vertebral fractures in elderly
      women with a recent hip fracture. The burden of vertebral fractures expressed by
      the Spinal Deformity Index (SDI) is more strictly associated with the
      trochanteric than the cervical localization of hip fracture and may influence
      short-term functional outcomes. INTRODUCTION: This study aimed to determine the
      prevalence and severity of vertebral fractures in elderly women with recent hip
      fracture and to assess whether the burden of vertebral fractures may be
      differently associated with trochanteric hip fractures with respect to cervical
      hip fractures. METHODS: We studied 689 Italian women aged 60 years or over with a
      recent low trauma hip fracture and for whom an adequate X-ray evaluation of spine
      was available. All radiographs were examined centrally for the presence of any
      vertebral deformities and radiological morphometry was performed. The SDI, which
      integrates both the number and the severity of fractures, was also calculated.
      RESULTS: Prevalent vertebral fractures were present in 55.7% of subjects and 95
      women (13.7%) had at least one severe fracture. The women with trochanteric hip
      fracture showed higher SDI and higher prevalence of diabetes with respect to
      those with cervical hip fracture, p=0.017 and p=0.001, respectively. SDI,
      surgical menopause, family history of fragility fracture, and type2 diabetes
      mellitus were independently associated with the risk of trochanteric hip
      fracture. Moreover, a higher SDI was associated with a higher percentage of post
      surgery complications (p=0.05) and slower recovery (p<0.05). CONCLUSIONS: Our
      study suggests that the burden of prevalent vertebral fractures is more strictly
      associated with the trochanteric than the cervical localisation of hip fracture
      and that elevated values of SDI negatively influence short term functional
      outcomes in women with hip fracture.

PMID- 23011682
TI  - Sport-specific association between exercise loading and the density, geometry,
      and microstructure of weight-bearing bone in young adult men.
AB  - In this population-based study of 24-year-old men, we have investigated the
      association between sport-specific exercise loading and different bone
      parameters. We reveal that the association between exercise loading and bone
      parameters is sport-specific, indicating that nonspecific resistance exercise
      does not impact bone density, geometry, or microstructure in young men.
      INTRODUCTION: In this cross-sectional study, the association between nonspecific
      resistive exercise and areal and volumetric bone density, bone geometry, or bone
      microstructure was investigated in young adult men. METHODS: A total of 184 male
      athletes, 24.0 +/- 0.6 years of age (mean +/- SD), representing nonspecific
      resistive exercise and soccer (proportion of recreational athletes, 93.4 and 7.7
      %, respectively), and 177 nonathletic age-matched controls were measured with
      dual-energy X-ray absorptiometry. Radius and tibia were measured by peripheral
      quantitative computed tomography (pQCT) at the diaphysis and by three-dimensional
      pQCT at the metaphysis. RESULTS: Men in the nonspecific resistive exercise group
      had higher grip strength(9.1 % or 0.4 SD) and higher lean mass(5.6 % or 0.5 SD)
      than those in the nonathletic group(p < 0.01 and p < 0.001, respectively).
      However, men who participated in nonspecific resistive exercise did not have
      higher bone density or a more favorable bone microstructure or geometry than
      their nonathletic referents. In contrast, men playing soccer had higher areal
      bone mineral density (aBMD) at the femoral neck (19.5 % or 1.2 SD) and lumbar
      spine (12.6 % or 1.0 SD), as well as larger cortical cross-sectional area (16.4 %
      or 1.1 SD) and higher trabecular bone volume fraction (14.5 % or 0.9 SD), as a
      result of increased trabecular number (8.7 % or 0.6 SD) and thickness (5.7 % or
      0.4 SD) at the tibia than men in the nonathletic group(p < 0.001). CONCLUSIONS:
      Weight-bearing exercise with impacts from varying directions (playing soccer) is
      associated with aBMD and volumetric BMD, cortical bone geometry, as well as
      trabecular microstructure of weight-bearing bone. Nonspecific recreational
      resistance exercise does not appear to be a strong determinant of bone density,
      geometry, or microstructure in young adult men.

PMID- 23011683
TI  - Effect of whole body vibration (WBV) therapy on bone density and bone quality in
      osteopenic girls with adolescent idiopathic scoliosis: a randomized, controlled
      trial.
AB  - The aim of this randomized controlled trial was to determine whether whole body
      vibration (WBV) therapy was effective for treating osteopenia in adolescent
      idiopathic scoliosis (AIS) patients. Results showed that WBV was effective for
      improving areal bone mineral density (aBMD) at the femoral neck of the dominant
      side and lumbar spine BMC in AIS subjects. INTRODUCTION: AIS is associated with
      osteopenia. Although WBV was shown to have skeletal anabolic effects in animal
      studies, its effect on AIS subjects remained unknown. The objective of this study
      was to determine whether WBV could improve bone mineral density (BMD) and bone
      quality for osteopenia in AIS subjects. METHODS: This was a randomized,
      controlled trial recruiting 149 AIS girls between 15 and 25 years old and with
      bone mineral density (BMD) Z-scores <-1. They were randomly assigned to the
      Treatment or Control groups. The Treatment group (n = 61) stood on a low
      magnitude high-frequency WBV platform 20 min/day, 5 days/week for 12 months. The
      Control group (n = 63) received observation alone. Bone measurement was done at
      baseline and at 12 months: (1) aBMD and BMC at femoral necks and lumbar spine
      using dual-energy X-ray absorptiometry (DXA) and (2) bone quality including bone
      morphometry, volumetric BMD (vBMD), and trabecular bone microarchitecture using
      high-resolution peripheral quantitative computed tomography (HR-pQCT) for
      nondominant distal radius and bilateral distal tibiae. RESULTS: The Treatment
      group had numerically greater increases in all DXA parameters with a
      statistically significant difference being detected for the absolute and
      percentage increases in femoral neck aBMD at the dominant leg (0.015 (SD =
      0.031)g/cm(2), 2.15 (SD = 4.32)%) and the absolute increase in lumbar spine BMC
      (1.17 (SD = 2.05)g) in the Treatment group as compared with the Control group
      (0.00084 (SD = 0.026)g/cm(2), 0.13 (SD = 3.62)% and 0.47 (SD = 1.88)g,
      respectively). WBV had no significant effect for other bone quality parameters.
      CONCLUSIONS: WBV was effective for improving aBMD at the femoral neck of the
      dominant side and lumbar spine BMC in AIS subjects.

PMID- 23011684
TI  - Age-dependent visuomotor performance and white matter structure: a DTI study.
AB  - The Trail Making Test (TMT), which assesses motor performance, selective
      attention, working memory and cognitive flexibility is highly sensitive to age
      related performance differences. However, the structural basis of this age
      performance association is largely unknown. This DTI study examined the influence
      of white matter characteristics on the association between TMT performance (i.e.,
      speed of processing) and age in a sample of 86 healthy, middle-aged subjects
      (mean age 27.9 years, range 18-55). Voxel-wise correlation yielded a significant
      negative association between FA in the body of the corpus callosum (CC) and TMT-A
      performance (i.e., time taken to complete the test). There was also a significant
      association between age and TMT-A performance. However, this association between
      age and TMT-A performance was neither mediated nor moderated by FA in the CC.
      Results suggest that fast motor performance is strongly dependent on individual
      white matter characteristics of the CC. This indicates that interindividual
      variations in white matter of the CC known to be relevant for interhemispheric
      motor signal transduction critically influence speed of motor processing.
      However, these interindividual variations do not explain the observed association
      between age and TMT performance. 

PMID- 23011687
TI  - The cover. Market church in Halle.

PMID- 23011690
TI  - NIH signals intent to boost funding of emergency care research and training.

PMID- 23011691
TI  - Petition targets painkiller marketing in effort to curb overdose deaths.

PMID- 23011692
TI  - Marijuana use starting in youth linked to IQ loss.

PMID- 23011698
TI  - Troponin levels and mortality after noncardiac surgery.

PMID- 23011699
TI  - Troponin levels and mortality after noncardiac surgery.

PMID- 23011701
TI  - Treatment of sepsis-related organ dysfunction.

PMID- 23011702
TI  - Treatment of sepsis-related organ dysfunction.

PMID- 23011704
TI  - Salary differences by gender.

PMID- 23011706
TI  - Use of information technology in the examination room.

PMID- 23011708
TI  - Bringing diagnosis into the quality and safety equations.

PMID- 23011709
TI  - Overcoming the pricing power of hospitals.

PMID- 23011710
TI  - Beyond joint implant registries: a patient-centered research consortium for
      comparative effectiveness in total joint replacement.

PMID- 23011711
TI  - A piece of my mind. Worlds apart.

PMID- 23011712
TI  - Perioperative dexamethasone administration and risk of bleeding following
      tonsillectomy in children: a randomized controlled trial.
AB  - CONTEXT: Corticosteroids are commonly given to children undergoing tonsillectomy
      to reduce postoperative nausea and vomiting; however, they might increase the
      risk of perioperative and postoperative hemorrhage. OBJECTIVE: To determine the
      effect of dexamethasone on bleeding following tonsillectomy in children. DESIGN,
      SETTING, AND PATIENTS: A multicenter, prospective, randomized, double-blind,
      placebo-controlled study at 2 tertiary medical centers of 314 children aged 3 to
      18 years undergoing tonsillectomy without a history of bleeding disorder or
      recent corticosteroid medication use and conducted between July 15, 2010, and
      December 20, 2011, with 14-day follow-up. We tested the hypothesis that
      dexamethasone would not result in 5% more bleeding events than placebo using a
      noninferiority statistical design. INTERVENTION: A single perioperative dose of
      dexamethasone (0.5 mg/kg; maximum dose, 20 mg), with an equivalent volume of 0.9%
      saline administered to the placebo group. MAIN OUTCOME MEASURES: Rate and
      severity of posttonsillectomy hemorrhage in the 14-day postoperative period using
      a bleeding severity scale (level I, self-reported or parent-reported
      postoperative bleeding; level II, required inpatient admission for postoperative
      bleeding; or level III, required reoperation to control postoperative bleeding).
      RESULTS: One hundred fifty-seven children (median [interquartile range] age, 6 [4
      8] years) were randomized into each study group, with 17 patients (10.8%) in the
      dexamethasone group and 13 patients (8.2%) in the placebo group reporting
      bleeding events. In an intention-to-treat analysis, the rates of level I bleeding
      were 7.0% (n = 11) in the dexamethasone group and 4.5% (n = 7) in the placebo
      group (difference, 2.6%; upper limit 97.5% CI, 7.7%; P for noninferiority = .17);
      rates of level II bleeding were 1.9% (n = 3) and 3.2% (n = 5), respectively
      (difference, -1.3%; upper limit 97.5% CI, 2.2%; P for noninferiority < .001); and
      rates of level III bleeding were 1.9% (n = 3) and 0.6% (n = 1), respectively
      (difference, 1.3%; upper limit 97.5% CI, 3.8%; P for noninferiority = .002).
      CONCLUSIONS: Perioperative dexamethasone administered during pediatric
      tonsillectomy was not associated with excessive, clinically significant level II
      or III bleeding events based on not having crossed the noninferior threshold of
      5%. Increased subjective (level I) bleeding events caused by dexamethasone could
      not be excluded because the noninferiority threshold was crossed. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01415583.

PMID- 23011713
TI  - Total knee arthroplasty volume, utilization, and outcomes among Medicare
      beneficiaries, 1991-2010.
AB  - CONTEXT: Total knee arthroplasty (TKA) is one of the most common and costly
      surgical procedures performed in the United States. OBJECTIVE: To examine
      longitudinal trends in volume, utilization, and outcomes for primary and revision
      TKA between 1991 and 2010 in the US Medicare population. DESIGN, SETTING, AND
      PARTICIPANTS: Observational cohort of 3,271,851 patients (aged >=65 years) who
      underwent primary TKA and 318 563 who underwent revision TKA identified in
      Medicare Part A data files. MAIN OUTCOME MEASURES: We examined changes in primary
      and revision TKA volume, per capita utilization, hospital length of stay (LOS),
      readmission rates, and adverse outcomes. RESULTS: Between 1991 and 2010 annual
      primary TKA volume increased 161.5% from 93,230 to 243,802 while per capita
      utilization increased 99.2% (from 31.2 procedures per 10,000 Medicare enrollees
      in 1991 to 62.1 procedures per 10,000 in 2010). Revision TKA volume increased
      105.9% from 9650 to 19,871 while per capita utilization increased 59.4% (from 3.2
      procedures per 10,000 Medicare enrollees in 1991 to 5.1 procedures per 10,000 in
      2010). For primary TKA, LOS decreased from 7.9 days (95% CI, 7.8-7.9) in 1991
      1994 to 3.5 days (95% CI, 3.5-3.5) in 2007-2010 (P < .001). For primary TKA,
      rates of adverse outcomes resulting in readmission remained stable between 1991
      2010, but rates of all-cause 30-day readmission increased from 4.2% (95% CI, 4.1%
      4.2%) to 5.0% (95% CI, 4.9%-5.0%) (P < .001). For revision TKA, the decrease in
      hospital LOS was accompanied by an increase in all-cause 30-day readmission from
      6.1% (95% CI, 5.9%-6.4%) to 8.9% (95% CI, 8.7%-9.2%) (P < .001) and an increase
      in readmission for wound infection from 1.4% (95% CI, 1.3%-1.5%) to 3.0% (95% CI,
      2.9%-3.1%) (P < .001). CONCLUSIONS: Increases in TKA volume have been driven by
      both increases in the number of Medicare enrollees and in per capita utilization.
      We also observed decreases in hospital LOS that were accompanied by increases in
      hospital readmission rates.

PMID- 23011714
TI  - How to use an article reporting a multiple treatment comparison meta-analysis.
AB  - Multiple treatment comparison (MTC) meta-analysis uses both direct (head-to-head)
      randomized clinical trial (RCT) evidence as well as indirect evidence from RCTs
      to compare the relative effectiveness of all included interventions. The
      methodological quality of MTCs may be difficult for clinicians to interpret
      because the number of interventions evaluated may be large and the methodological
      approaches may be complex. Clinicians and others evaluating an MTC should be
      aware of the potential biases that can affect the interpretation of these
      analyses. Readers should consider whether the primary studies are sufficiently
      homogeneous to combine; whether the different interventions are sufficiently
      similar in their populations, study designs, and outcomes; and whether the direct
      evidence is sufficiently similar to the indirect evidence to consider combining.
      This article uses the existing Users' Guides format to address study validity,
      interpretation of results, and application to a patient scenario.

PMID- 23011716
TI  - A florid, tiny, discrete eruption on the penis.

PMID- 23011715
TI  - Caring for the older person with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD), a common disease in elderly
      patients, is characterized by high symptom burden, health care utilization,
      mortality, and unmet needs of patients and caregivers. Respiratory failure and
      dyspnea may be exacerbated by heart failure, pulmonary embolism, and anxiety; by
      medication effects; and by other conditions, including deconditioning and
      malnutrition. Randomized controlled trials, which provide the strongest evidence
      for guideline recommendations, may underestimate the risk of adverse effects of
      interventions for older patients with COPD. The focus of guidelines on disease
      modifying therapies may not address the full spectrum of patient and caregiver
      needs, particularly the high rates of bothersome symptoms, risk of functional and
      cognitive decline, and need for end-of-life care planning. Meeting the many needs
      of older patients with COPD and their families requires that clinicians
      supplement guideline-recommended care with treatment decision making that takes
      into account older persons' comorbid conditions, recognizes the trade-offs
      engendered by the increased risk of adverse events, focuses on symptom relief and
      function, and prepares patients and their loved ones for further declines in the
      patient's health and their end-of-life care. A case of COPD in an 81-year-old man
      hospitalized with severe dyspnea and respiratory failure highlights both the
      challenges in managing COPD in the elderly and the limitations in applying
      guidelines to geriatric patients.

PMID- 23011717
TI  - Increasing use of total knee replacement and revision surgery.

PMID- 23011720
TI  - JAMA patient page. Chronic obstructive pulmonary disease.

PMID- 23011721
TI  - Tip apex distance, hip screw placement, and neck shaft angle as potential risk
      factors for cut-out failure of hip screws after surgical treatment of
      intertrochanteric fractures.
AB  - PURPOSE: To describe the quality of osteosynthesis after intertrochanteric
      fractures evaluation of tip apex distance (TAD) and position of the hip screw
      have been established. Furthermore, a slightly valgus fracture reduction has been
      suggested to reduce the risk of cut-out failure. However, uniform recommendations
      for optimal screw positioning and fracture reduction are still missing. The
      purpose of our study was to confirm potential risk factors for cut-out of hip
      screws of intertrochanteric fractures and to provide recommendations for
      practical clinical use. METHODS: A retrospective analysis of all patients with
      intertrochanteric fractures treated with a DHS or a gamma nail between January of
      2007 and May of 2010 was performed at a level I trauma center. RESULTS: Two
      hundred thirty-five patients with intertrochanteric fractures after intra- and
      extramedullary stabilization were analyzed. A TAD of more than 25 mm was
      demonstrated to be the most important factor for cut-out in stable and unstable
      fractures. Fracture reduction with a valgus NSA of 5-10 degrees  was associated
      with a trend towards a lower rate of screw cut-out while an anterior placement of
      the screw (Parker's ratio index of <40) significantly increased cut-out
      incidence. CONCLUSIONS: According to our results, the TAD should not exceed 25 mm
      in stable (AO/OTA A1) as well as unstable (AO/OTA A2) fractures. An increased
      anterior hip screw placement should be avoided while fracture reduction with a
      slight valgus Neck Shaft seems favorable.

PMID- 23011722
TI  - Are we evaluating osteonecrosis adequately?
AB  - PURPOSE: It is well recognised that to evaluate a patient with osteonecrosis of
      the femoral head (ONFH) adequately, it is necessary that the size of the infarct
      and the extent of femoral head joint involvement be indicated, in addition to the
      type or stage of the pathological process. The purpose of this study was to
      determine whether patients with ONFH are being evaluated adequately in studies
      published during the past 25 years and to see if any trends can be identified.
      METHODS: Articles describing treatment of patients with ONFH, published between
      1985 and 2011, were reviewed to determine the methods used to indicate the type
      and extent of pathology present on radiographs and magnetic resonance imaging
      (MRI) studies. The classification systems cited were identified and divided
      between those which indicated only the stage and those which indicated both stage
      and extent of involvement. RESULTS: In 208 studies published between 1985 and
      2011, specific classification systems were cited 237 times. During this period,
      non-quantitative systems, which only indicate stage, were cited 139 times (59 %)
      and quantitative systems, which indicate both stage and extent of involvement
      were cited 77 times (32 %). Between 2006 and 2011, non-quantitative systems were
      cited 30 times (48 %) and quantitative systems were cited 27 times (44 %).
      CONCLUSIONS: During the past 25 years there has been a trend towards the use of
      more comprehensive and effective methods of evaluating patients with ONFH.
      However, during the past five years, approximately half of the published studies
      continued to use limited, non-quantitative methods of evaluation. This should be
      brought to the attention of the orthopaedic community. Future investigations and
      publications on ONFH should employ comprehensive methods of classification which
      include not only the stage of disease but also measurements of the size of the
      necrotic segment and the extent of femoral head and joint involvement.

PMID- 23011723
TI  - Medullary thyroid cancer--current treatment strategy, novel therapies and
      perspectives for the future.
AB  - Medullary thyroid cancer (MTC), an uncommon and slow-growing tumor, is difficult
      to eradicate when metastasis or recurrence develops. This review describes
      therapeutic approaches to patients with recurrent sporadic MTC, management of
      advanced cases of MTC, and future treatment options. A literature review of
      treatment of MTC in humans was conducted. Surgery is currently the only
      potentially curative treatment for MTC; complete tumor resection and removal of
      suspicious nodes is the most important initial treatment to prevent recurrence
      and metastasis. When recurrence or metastatic MTC develops, the decision for
      continued observation or initiation of systemic therapy is based on the degree of
      tumor aggressiveness. Lymph node involvement, calcitonin doubling time, types of
      RET mutation, and tumor stage are factors that help determine the need for
      further treatment. Therapeutic options for aggressive and inoperable MTC
      primarily include tyrosine kinase inhibitors, external beam radiation therapy, or
      other medications. Among tyrosine kinase inhibitors, vandetanib is the first drug
      that is FDA approved for treatment of MTC. Focused external beam radiation
      therapy can be reconsidered for patients with cervical node involvement. Although
      other targeted drug therapies have been tried, definitive clinical studies are
      lacking. In recurrent or advanced MTC, when systemic therapy is warranted,
      vandetanib is available for use in treatment; however, side effects of this drug
      can be problematic, and impact on overall survival is presently unknown. Newer
      therapeutics are being studied with the goal of balancing control of tumor growth
      with maintaining the patient's quality of life.

PMID- 23011724
TI  - Body size in relation to urinary estrogens and estrogen metabolites (EM) among
      premenopausal women during the luteal phase.
AB  - Estrogen metabolism profiles may play an important role in the relationship
      between body size and breast carcinogenesis. Previously, we observed inverse
      associations between current body mass index (BMI) and plasma levels of parent
      estrogens (estrone and estradiol) among premenopausal women during both
      follicular and luteal phases. Using data from the Nurses' Health Study II, we
      assessed whether height, current BMI, and BMI at age 18 were associated with the
      urinary concentrations of 15 estrogens and estrogen metabolites (jointly referred
      to as EM) measured during the luteal phase among 603 premenopausal women. We
      observed inverse associations with total EM for height (P (trend) = 0.01) and
      current BMI (P (trend) = 0.01), but not BMI at age 18 (P (trend) = 0.26). Six EMs
      were 18-27% lower in women with a height 68+ versus <=62 in., primarily in the
      methylated catechol pathway (P (trend) = 0.04). Eight EMs were 18-50% lower in
      women with a BMI of 30+ versus <20, primarily in the 2-catechol and methylated
      catechol pathways (P (trend) < 0.001 for both). Our results suggest that height
      and current BMI are associated with estrogen metabolism profiles in premenopausal
      women. Further studies with timed urine and blood collections are required to
      confirm and extend our findings.

PMID- 23011725
TI  - IGFBP-3 nuclear localization predicts human prostate cancer recurrence.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is a pro-apoptotic, anti
      metastasic, and anti-angiogenic protein. Low serum IGFBP-3 has been associated
      with risk of more aggressive prostate cancer (PCa). We investigated the impact of
      nuclear and cytoplasmic IGFBP-3 protein expression levels in PCa by examining
      their in situ expression across a wide spectrum of primary tumors by
      immunohistochemical analysis of tissue microarrays. Immunohistochemistry was
      performed on PCa microarrays constructed from 226 hormone naive patients who
      underwent radical prostatectomy. Both cytoplasmic and nuclear IGFBP-3 expressions
      were scored in a semi-quantitative fashion using an integrated measure of
      intensity and positivity. The distribution of IGFBP-3 protein expression was
      examined across the spectrum of epithelial tissues, and its association with
      standard clinicopathological covariates and tumor recurrence was examined. There
      was a broad range of IGFBP-3 staining across all histologies examined. Tumor had
      higher IGFBP-3 cytoplasmic and nuclear staining than benign histologies. For
      IGFBP-3 nuclear staining, PCa was significantly different than benign prostatic
      hyperplasia, normal prostate, and prostate intraepithelial neoplasia. As both a
      continuous and dichotomized variable, higher nuclear IGFBP-3 expression had
      statistically significant associations with PCa recurrence. The cytoplasmic
      staining had no significance in any patient subgroup. In patients with low-grade
      cancer, IGFBP-3 nuclear positivity was a better predictor of recurrence than
      baseline PSA, tumor margin status, TNM tumor stage, or presence of capsular
      invasion. High nuclear IGFBP-3 is amongst the strongest predictors of cancer
      recurrence in patients with low-grade prostate cancers and may therefore play an
      important role in risk stratification.

PMID- 23011727
TI  - Reduced incidence of lower-extremity amputations in people with diabetes in
      Scotland: a nationwide study.
AB  - OBJECTIVE: To establish the incidence of nontraumatic lower-extremity amputation
      (LEA) in people with diabetes in Scotland. RESEARCH DESIGN AND METHODS: This
      cohort study linked national morbidity records and diabetes datasets to establish
      the number of people with diabetes who underwent nontraumatic major and minor LEA
      in Scotland from 2004 to 2008. RESULTS: Two thousand three hundred eighty-two
      individuals with diabetes underwent a nontraumatic LEA between 2004 and 2008;
      57.1% (n = 1,359) underwent major LEAs. The incidence of any LEA among persons
      with diabetes fell over the 5-year study period by 29.8% (3.04 per 1,000 in 2004
      to 2.13 per 1,000 in 2008, P < 0.001). Major LEA rates decreased by 40.7% from
      1.87 per 1,000 in 2004 to 1.11 per 1,000 in 2008 (P < 0.001). CONCLUSIONS: There
      has been a significant reduction in the incidence of LEA in persons with diabetes
      in Scotland between 2004 and 2008, principally explained by a reduction in major
      amputation.

PMID- 23011726
TI  - The diabetes drug liraglutide ameliorates aberrant insulin receptor localisation
      and signalling in parallel with decreasing both amyloid-beta plaque and glial
      pathology in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) has been shown to involve desensitised insulin receptor
      (IR) signalling. Liraglutide, a novel glucagon-like peptide 1 (GLP-1) analogue
      that facilitates insulin signalling, is currently approved for use in type 2
      diabetes mellitus. In the present study, we show that distinctive alterations in
      the localisation and distribution of the IR and increased levels of insulin
      receptor substrate (IRS)-1 phosphorylated at serine 616 (IRS-1 pS(616)), a key
      marker of insulin resistance, are associated with amyloid-beta plaque pathology
      in the frontal cortex of a mouse model of AD, APPSWE/PS1dE9. Altered IR status in
      APPSWE/PS1dE9 is most evident in extracellular deposits with the appearance of
      dystrophic neurites, with significantly increased IRS-1 pS(616) levels detected
      within neurons and neurites. The IR and IRS-1 pS(616) changes occur in the
      vicinity of all plaques in the APPSWE/PS1dE9 brain, and a significant
      upregulation of astrocytes and microglia surround this pathology. We show that
      liraglutide treatment for 8 weeks at 25 nmol/kg body weight i.p. once daily in 7
      month-old mice significantly decreases IR aberrations in conjunction with a
      concomitant decrease in amyloid plaque load and levels of IRS-1 pS(616).
      Liraglutide also induces a highly significant reduction in astrocytosis and
      microglial number associated with both plaques and IR pathology. The amelioration
      of IR aberrations and attenuation of IRS-1 pS(616) upregulation, plaque and glial
      activation in APPSWE/PS1dE9 mice treated with liraglutide support the
      investigation of the therapeutic potential of liraglutide and long-lasting GLP-1
      agonists in patients with AD.

PMID- 23011728
TI  - Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter
      2, improves serum glucose profiles in type 1 diabetes.
AB  - OBJECTIVE: Remogliflozin etabonate (RE), an inhibitor of the sodium-glucose
      transporter 2, improves glucose profiles in type 2 diabetes. This study assessed
      safety, tolerability, pharmacokinetics, and pharmacodynamics of RE in subjects
      with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ten subjects managed with
      continuous subcutaneous insulin infusion were enrolled. In addition to basal
      insulin, subjects received five randomized treatments: placebo, prandial insulin,
      50 mg RE, 150 mg RE, and mg RE 500. RESULTS: Adverse events and incidence of
      hypoglycemia with RE did not differ from placebo and prandial insulin groups. RE
      significantly increased urine glucose excretion and reduced the rise in plasma
      glucose concentration after oral glucose. RE reduced incremental adjusted
      weighted mean glucose (0-4 h) values by 42-49 mg/dL and mean glucose (0-10 h) by
      52-69 mg/dL. CONCLUSIONS: RE can be safely administered with insulin in type 1
      diabetes and reduces plasma glucose concentrations compared with placebo.

PMID- 23011730
TI  - A myotonic dystrophy 1 patient complicated with placental adherence after
      miscarriage of one dichorionic diamniotic twin following her tenth in vitro
      fertilization and embryo transfer.

PMID- 23011729
TI  - Quantitative measurements and modeling of cargo-motor interactions during fast
      transport in the living axon.
AB  - The kinesins have long been known to drive microtubule-based transport of sub
      cellular components, yet the mechanisms of their attachment to cargo remain a
      mystery. Several different cargo-receptors have been proposed based on their in
      vitro binding affinities to kinesin-1. Only two of these-phosphatidyl inositol, a
      negatively charged lipid, and the carboxyl terminus of the amyloid precursor
      protein (APP-C), a trans-membrane protein-have been reported to mediate motility
      in living systems. A major question is how these many different cargo, receptors
      and motors interact to produce the complex choreography of vesicular transport
      within living cells. Here we describe an experimental assay that identifies cargo
      motor receptors by their ability to recruit active motors and drive transport of
      exogenous cargo towards the synapse in living axons. Cargo is engineered by
      derivatizing the surface of polystyrene fluorescent nanospheres (100 nm diameter)
      with charged residues or with synthetic peptides derived from candidate motor
      receptor proteins, all designed to display a terminal COOH group. After injection
      into the squid giant axon, particle movements are imaged by laser-scanning
      confocal time-lapse microscopy. In this report we compare the motility of
      negatively charged beads with APP-C beads in the presence of glycine-conjugated
      non-motile beads using new strategies to measure bead movements. The ensuing
      quantitative analysis of time-lapse digital sequences reveals detailed
      information about bead movements: instantaneous and maximum velocities, run
      lengths, pause frequencies and pause durations. These measurements provide
      parameters for a mathematical model that predicts the spatiotemporal evolution of
      distribution of the two different types of bead cargo in the axon. The results
      reveal that negatively charged beads differ from APP-C beads in velocity and
      dispersion, and predict that at long time points APP-C will achieve greater
      progress towards the presynaptic terminal. The significance of this data and
      accompanying model pertains to the role transport plays in neuronal function,
      connectivity, and survival, and has implications in the pathogenesis of
      neurological disorders, such as Alzheimer's, Huntington and Parkinson's diseases.

PMID- 23011731
TI  - Could serum beta-hCG levels and gestational age be the indicative factors for the
      prediction of the degree of trophoblastic invasion into tubal wall in unruptured
      ampullary pregnancies?
AB  - OBJECTIVE: To evaluate the predictive value of gestational age and maternal serum
      beta-hCG concentration for the determination of the depth of trophoblastic
      invasion into the tubal wall. METHODS: This is a retrospective trial conducted on
      women with a diagnosis of ampullary pregnancy (71) who were submitted to
      salpingectomy. Serum beta-hCG measurements were obtained at the initial admission
      of hospital. Histological investigation was performed by a single well
      experienced pathologist who was blind to the clinical and laboratory
      characteristics of the patients. Ampullary pregnancy was classified
      histologically according to the depth of trophoblastic infiltration into tubal
      wall: trophoblast limited to the tubal mucosa (stage I), extended to muscularis
      layer (stage II) and complete tubal wall infiltration up to serosal layer (stage
      III). RESULTS: There was a significant difference in maternal serum beta-hCG
      concentrations regarding the histological stages of trophoblastic invasion. The
      serum beta-hCG concentrations that the best predicted for stage III trophoblastic
      invasion was 6,475 mIU/ml, with a sensitivity of 100 %, a specificity of 92 %.
      CONCLUSION: The depth of trophoblastic tissue infiltration into tubal wall is
      correlated with serum beta-hCG levels, but not with gestational age. These
      findings may explain the reason for conservative management failure of EP in
      women with high beta-hCG concentrations.

PMID- 23011732
TI  - The burden of anaemia and associated factors in HIV positive Nigerian women.
AB  - BACKGROUND: Anaemia is the most common complication of pregnancy and a predictor
      of poor maternal and foetal outcomes. HIV infection is now recognized as one of
      the major contributors to anaemia in pregnancy. It is therefore important to
      determine the burden and risk factors of anaemia in maternal HIV infection in
      others to plan effective prevention strategies as well as optimize management
      outcomes. OBJECTIVE: To determine the prevalence and risk factors of anaemia in
      pregnant HIV positive Nigerians. METHODS: The prevalence and possible risk
      factors of anaemia were investigated in HIV positive pregnant Nigerian women at a
      large HIV treatment clinic in southwestern Nigeria using a cross-sectional design
      between January 2006 and December 2011. RESULTS: Nine hundred and eighty-five
      (42.5 %) women of 2,318 HIV positive pregnant women seen during the period were
      anaemic by WHO standard defined by haemoglobin <11 g/dl. Majority were of mild to
      moderate severity (97.9 %). Short inter birth interval (p = 0.002), presence of
      opportunistic infections (OIs), (p = 0.001), use of zidovudine containing regimen
      (p = 0.0005) and CD4 cell count <200 cells/mm(3) (p = 0.001) were found to be
      independently associated with anaemia in HIV positive pregnant women after
      controlling for confounding variables. CONCLUSION: Anaemia was found to be high
      at 42.5 % among the HIV positive women studied and was found to be independently
      associated with short inter birth interval, presence of OIs, advanced HIV disease
      and use of zidovudine containing HAART regimen.

PMID- 23011733
TI  - Social determinants of health associated with cervical cancer screening among
      women living in developing countries: a scoping review.
AB  - INTRODUCTION: Thousands of women living in many middle and low-income countries
      are unnecessarily dying from cervical cancer, partly due to limited screening
      coverage. OBJECTIVES: To identify social determinants of health (SDH) associated
      with cervical screening for women living in middle and low-income countries, to
      inform responses to improve SDH and screening coverage, and to identify research
      gaps. METHODS: A scoping literature review. We located original research articles
      on SDH associated with cervical cancer screening through bibliographic databases,
      supplemented by hand searching (n=166+4). Included were those conducted in middle
      and low-income countries and published in English, Portuguese and Spanish
      academic journals between January 2000 and June 2011 (n=37). Excluded were those
      from high-income countries or focusing on screening-diagnostic techniques or HPV
      vaccine. Narrative synthesis examined the results in relation to a SDH framework.
      RESULTS: A number of factors influence access along the pathway to cervical
      cancer screening. Structural (cultural and societal values, socioeconomic
      position, ethnicity), intermediary (geographic location, health seeking
      behaviours, psychosocial factors, nature of the health system), and cross-cutting
      (social cohesion) SDH were all important. No single factor could entirely explain
      the observed cervical screening patterns. CONCLUSION: Cervical cancer screening
      among women living in middle and low-income countries are influenced by the
      interaction among several different SDH. The majority of researchers studying
      cervical cancer screening focused on exploring single socio-demographic
      variables, which is typical of positivist, biomedical and epidemiological
      research. An inter-sectionality approach may provide a richer understanding of
      the complexities that influence women's pathways to cervical cancer screening and
      assist design of international programmes and policies from a social justice
      perspective.

PMID- 23011734
TI  - Are cystatin C-based equations superior to creatinine-based equations for
      estimating GFR in Chinese elderly population?
AB  - PURPOSE: Cystatin C has been proposed as a surrogate marker of kidney function.
      The elderly population accounts for the largest proportion of chronic kidney
      disease (CKD) patients. The aim of this study was to assess the diagnostic value
      of serum cystatin C and compare the applicability of cystatin C-based equations
      with serum creatinine (Scr)-based equations for estimating glomerular filtration
      rate (GFR). METHODS: The estimated GFR (eGFR) values from six cystatin C-based
      equations (Tan, MacIsaac, Ma, Stevens1-3) and three Scr-based equations (CG,
      MDRD, CKD-EPI) were compared with the reference GFR (rGFR) values from 99mTc-DTPA
      renal dynamic imaging method. RESULTS: A total of 110 elderly Chinese (60-92
      year, 71.05+/-7.62 year) were enrolled. Cystatin C had better diagnostic value
      than Scr (relationship coefficient with rGFR: cystatin C -0.847 vs. Scr -0.729,
      P<0.01; sensitivity: cystatin C 0.90 vs. Scr 0.55, P<0.01; AUCROC: cystatin C
      0.857 vs. Scr 0.757, P<0.01). All the equations predicted GFR more accurately for
      rGFR>=60 ml/min/1.73 m2 than for rGFR<60 ml/min/1.73 m2. Most equations had
      acceptable accuracy. The cystatin C-based equations deviated from rGFR by -12.78
      ml/min/1.73 m2 to -2.12 ml/min/1.73 m2, with accuracy varying from 64.6 to 82.7%.
      The Scr-based equations deviated from rGFR by -5.37 ml/min/1.73 m2 to -0.68
      ml/min/1.73 m2, with accuracy varying from 77.3 to 79.1%. The CKD-EPI, MacIsaac
      and Ma equations predicted no bias with rGFR (P>0.05), with higher accuracy and
      lower deviation in the total group. The MacIsaac, CKD-EPI and Stevens3 equations
      could be optimal for those with normal and mildly impaired kidney function,
      whereas the Ma equation for those with CKD. CONCLUSION: Cystatin C is a promising
      kidney function marker. However, not all cystatin C-based equations could be
      superior to the Scr-equations.

PMID- 23011735
TI  - [Acute inner ear loss with facial paresis and severe headache].

PMID- 23011736
TI  - [Differential diagnosis of a lymph node metastasis in carcinoma of unknown
      primary].

PMID- 23011737
TI  - Incarcerated inguinal hernia and small bowel obstruction as a rare complication
      of a penile prosthesis.
AB  - In this paper, we present a rare case of a small bowel obstruction secondary to
      an incarcerated inguinal hernia as a short-term complication of a penile
      prosthesis implantation. The patient underwent prosthesis implantation to treat
      refractory erectile dysfunction after a robotic-assisted laparoscopic radical
      prostatectomy. He presented 2 weeks later with the incarcerated hernia to our
      emergency department and surgical service. The hernia was repaired in a tension
      free manner, and the bowel was uncompromised. The patient is symptom free at
      follow-up.

PMID- 23011738
TI  - Comparison of mesh-plug and Lichtenstein for inguinal hernia repair: a meta
      analysis of randomized controlled trials. Li J, Ji Z, Li Y. Hernia 2012 Jul 28.
      doi: 10.1007/s10029-012-0974-6.

PMID- 23011739
TI  - Mentha piperita as a pivotal neuro-protective agent against gamma irradiation
      induced DNA fragmentation and apoptosis : Mentha extract as a neuroprotective
      against gamma irradiation.
AB  - Ionizing radiation is classified as a potent carcinogen, and its injury to living
      cells, in particular to DNA, is due to oxidative stress enhancing apoptotic cell
      death. Our present study aimed to characterize and semi-quantify the radiation
      induced apoptosis in CNS and the activity of Mentha extracts as neuron-protective
      agent. Our results through flow cytometry exhibited the significant disturbance
      and arrest in cell cycle in % of M1: SubG1 phase, M2: G0/1 phase of diploid
      cycle, M3: S phase and M4: G2/M phase of cell cycle in brain tissue (p < 0.05).
      Significant increase in % of apoptosis and P53 protein expression as apoptotic
      biomarkers were coincided with significant decrease in Bcl(2) as an anti
      apoptotic marker. The biochemical analysis recorded a significant decrease in the
      levels of reduced glutathione, superoxide dismutase, deoxyribonucleic acid (DNA)
      and ribonucleic acid contents. Moreover, numerous histopathological alterations
      were detected in brain tissues of gamma irradiated mice such as signs of
      chromatolysis in pyramidal cells of cortex, nuclear vacuolation, numerous
      apoptotic cell, and neural degeneration. On the other hand, gamma irradiated mice
      pretreated with Mentha extract showed largely an improvement in all the above
      tested parameters through a homeostatic state for the content of brain apoptosis
      and stabilization of DNA cycle with a distinct improvement in cell cycle analysis
      and antioxidant defense system. Furthermore, the aforementioned effects of Mentha
      extracts through down-regulation of P53 expression and up-regulation of Bcl(2)
      domain protected brain structure from extensive damage. Therefore, Mentha extract
      seems to have a significant role to ameliorate the neuronal injury induced by
      gamma irradiation.

PMID- 23011740
TI  - Impact of chicken-origin cells on adaptation of a low pathogenic influenza virus.
AB  - Understanding the growth dynamics of influenza viruses is an essential step in
      virus replication and cell-adaptation. The aim of this study was to elucidate the
      growth kinetic of a low pathogenic avian influenza H9N2 subtype in chicken embryo
      fibroblast (CEF) and chicken tracheal epithelial (CTE) cells during consecutive
      passages. An egg-adapted H9N2 virus was seeded into both cell culture systems.
      The amount of infectious virus released into the cell culture supernatants at
      interval times post-infection were titered and plaque assayed. The results as
      well as cell viability results indicate that the infectivity of the influenza
      virus was different among these primary cells. The egg-adapted H9N2 virus
      featured higher infectivity in CTE than in CEF cells. After serial passages and
      plaque purifications of the virus, a CTE cell-adapted strain was generated which
      carried amino acid substitutions within the HA stem region. The strain showed
      faster replication kinetics in cell culture resulting in an increase in virus
      titer. Overall, the present study provides the impact of cell type, multiplicity
      of infection, cellular protease roles in virus infectivity and finally molecular
      characterization during H9N2 virus adaptation procedure.

PMID- 23011741
TI  - Evaluation of isolation methods and culture conditions for rat bone marrow
      mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (bMSCs) are multipotent and preferred for cell
      therapy. However, the content of bMSCs is very low. To propagate a large number
      of primary bMSCs rapidly has become a prerequisite for bMSC study and
      application. Different methods of isolating and culturing bMSC were used and
      compared among groups: bMSCs of group A are isolated using direct adherence
      method and cultured by conventional medium changing; of group B are isolated
      using direct adherence method and cultured by low volume medium changing; of
      group C are isolated using density gradient centrifugation and cultured by
      conventional medium changing; of group D are isolated using density gradient
      centrifugation and cultured by low volume medium changing. The average population
      doubling time (PDT), average generation time and the cumulative cell doubling
      level were calculated for every group. bMSCs cultured with complete medium
      containing 10, 11 and 15 % FBS were allocated into group a, b and c separatedly.
      Cell numbers were counted everyday under a microscope, the population doubling
      level curve was plotted and PDT was calculated. The growth curve of bMSC in group
      a, b and c was made. Both density gradient centrifugation and direct adherence
      methods obtained relatively pure bMSCs. A larger quantity of primary bMSCs were
      obtained by direct adherence. bMSC proliferation was faster when cultured via the
      low volume medium changing method at a serum concentration of 11 % than the other
      methods. Isolating bMSC by direct adherence and culturing by low volume medium
      changing at a serum concentration of 11 % is preferential for bMSC propagation.

PMID- 23011742
TI  - Ambulatory blood pressure monitoring in pediatric renal transplantation.
AB  - Hypertension is a common and serious complication after renal transplantation. It
      is an important risk factor for graft loss and adverse cardiovascular outcomes.
      Blood pressure (BP) in transplanted children should be measured not only by
      clinic BP (cBP) measurement, but also by ambulatory blood pressure monitoring
      (ABPM), because ABPM has distinct advantages over cBP, specifically the ability
      to reveal nocturnal, masked or white-coat hypertension. These types of
      hypertension are common in transplanted children (nocturnal hypertension 36-71 %,
      masked hypertension 24-45 %). It may also reveal uncontrolled hypertension in
      treated children, thereby improving control of hypertension. Regular use of ABPM
      and ABPM-guided therapy of hypertension may help to decrease cardiovascular and
      renal target organ damage in transplanted children. Therefore, ABPM should be
      routinely performed in all transplanted children at least once a year, regardless
      of the values of cBP.

PMID- 23011743
TI  - Novel antihypertensive therapies: renal sympathetic nerve ablation and carotid
      baroreceptor stimulation.
AB  - Therapeutic interventions aimed at reducing high blood pressure still encompass a
      number of difficulties and limitations. This is the case particularly in
      resistant hypertension, i.e. a condition characterized by a very high
      cardiovascular risk. Carotid baroreceptor stimulation and renal sympathetic
      nerves ablation represent new approaches in the treatment of this condition. This
      paper will provide a comparison of the effects of the two procedures,
      highlighting their effects on blood pressure, metabolic profile, target organ
      damage, safety and tolerability profile.

PMID- 23011744
TI  - Craniofacial morphology but not excess body fat is associated with risk of having
      sleep-disordered breathing--the PANIC Study (a questionnaire-based inquiry in 6-8
      year-olds).
AB  - We investigated the associations of dental occlusion, other craniofacial features
      and body fat with paediatric sleep-disordered breathing (SDB) in a representative
      population sample of 491 Finnish children 6-8 years of age. Overweight and
      obesity were defined using age- and sex-specific body mass index cutoffs by
      International Obesity Task Force (IOTF) criteria. Body fat percentage was
      assessed by dual-energy X-ray absorptiometry. Facial proportions, dental
      occlusion and soft tissue structures were evaluated by an orthodontist. Sleep was
      assessed by a sleep questionnaire administered by the parents. SDB was defined as
      apnoeas, frequent or loud snoring or nocturnal mouth breathing observed by the
      parents. The prevalence of SDB was 9.9 % with no difference between boys and
      girls. The median (interquartile range) of body fat percentage was 20.6 (17.4
      27.1) in girls and 15.0 (11.4-21.6) in boys. Altogether 11.4 % of boys and 15.6 %
      of girls were classified as having overweight or obesity according to the IOTF
      criteria. There was no difference in the prevalence of overweight, obesity or
      body fat percentage between children with SDB and those without it. Children with
      tonsillar hypertrophy had a 3.7 times higher risk of suffering SDB than those
      with normal size tonsils after adjustment for age, sex and body fat percentage.
      Furthermore, children with cross bite had a 3.3 times higher risk of having SDB
      than those without cross bite, and children with a convex facial profile had a
      2.6 times higher risk of having SDB than those with a normal facial profile.
      CONCLUSION: Abnormal craniofacial morphology, but not excess body fat, is
      associated with an increased risk of having SDB in 6-8-year-old children. A
      simple model of necessary clinical examinations (i.e. facial profile, dental
      occlusion and tonsils) is recommended to recognize children with an increased
      risk of SDB.

PMID- 23011745
TI  - An analysis of successful litigation claims in childhood fatalities in England.
AB  - This study aimed to analyse the number, nature and costs of successful litigation
      claims against the National Health Service in England involving fatalities in
      children. A record of claims involving fatalities in children from 1 April 2004
      to 31 March 2011 was obtained from the National Health Service Litigation
      Authority. The closed cases where compensation had been paid to the claimant were
      analysed. One hundred thirty out of a total of 234 closed cases (56 %) resulted
      in payment of compensation. The commonest causes of a fatality were
      delayed/failed diagnosis (58), delayed/failed treatment (19), complications
      related to procedures/operations (17), poor overall quality of care (7),
      medication errors (6), inappropriate medical advice leading to delayed
      presentation (6) and communication errors (5). The commonest diagnoses involved
      were sepsis (17), meningitis (11), cardiac defects (8), gastrointestinal illness
      (8), intracranial bleed (4), meningococcal septicaemia (3) and malignancy (3).
      The total cost of litigation was L8,143,342 with cost per case ranging from L1607
      to L790,555 with a mean of L62,641. The death of a child is a tragedy. When an
      error has occurred, this causes further suffering to the family and to the health
      care professionals involved. CONCLUSION: This data suggest areas where training
      could be improved, and by learning from such errors we can diminish such
      occurrences in the future and improve patient safety.

PMID- 23011746
TI  - A unique case of right-sided Poland syndrome with true dextrocardia and total
      situs inversus.
AB  - Poland syndrome has been reported to be associated with true dextrocardia, but
      not with true situs inversus. In this report, we describe the first patient with
      total situs inversus in medical literature and try to highlight the syndrome's
      probable etiology and pathogenetic mechanisms in utero.

PMID- 23011747
TI  - Factors associated with iatrogenesis in neonatal intensive care units: an
      observational multicenter study.
AB  - The objective of our study was to assess factors associated with iatrogenic
      events in Neonatal Intensive Care Units (NICUs). This was a retrospective
      analysis based on a cohort of patients who participated in our previous
      prospective study (Pediatrics 122:550-555, 2008), conducted in four tertiary
      university-affiliated NICUs in Israel, that included all consecutive infants (n =
      615) hospitalized during the study period. Ongoing monitoring of iatrogenic
      events was performed by designated "iatrogenesis advocates." The main outcome
      measures were the association of individual infant characteristics and NICUs'
      environmental characteristics with iatrogenic events assessed by univariate and
      multiple logistic regression analysis. We found that four infant characteristics
      were significantly (p < 0.001) associated with iatrogenic events in a univariate
      analysis: gestational age, birth weight, severity of initial illness as assessed
      by the Score for Neonatal Acute Physiology and Perinatal Extension (SNAPPE II),
      and length of stay (LOS). All four factors demonstrated a significant (p < 0.001)
      dose-response relationship with iatrogenic events. Univariate analysis for
      environmental characteristics showed that type of shift, but not nursing
      workload, was significantly associated with iatrogenic events (p < 0.001). In a
      multiple logistic regression analysis, only LOS (adjusted OR 1.02 [95 % CI, 1.01
      1.03]) and type of shift, morning vs. evening (adjusted OR 3.44 [95 % CI, 2.33
      5.08]) and morning vs. night (adjusted OR 6.07 [95 % CI, 3.86-9.56]), remained
      independently associated with iatrogenic events (p < 0.001). Prolonged LOS and
      morning shifts were found to be significantly associated with iatrogenic events.
      Further prospective research is warranted to identify the specific causes for
      iatrogenic events in order to target active interventions to prevent them.

PMID- 23011748
TI  - FliA expression analysis and influence of the regulatory proteins RpoN, FleQ and
      FliA on virulence and in vivo fitness in Legionella pneumophila.
AB  - In Legionella pneumophila, the regulation of the flagellum and the expression of
      virulence traits are linked. FleQ, RpoN and FliA are the major regulators of the
      flagellar regulon. We demonstrated here that all three regulatory proteins
      mentioned (FleQ, RpoN and FliA) are necessary for full in vivo fitness of L.
      pneumophila strains Corby and Paris. In this study, we clarified the role of FleQ
      for fliA expression from the level of mRNA toward protein translation. FleQ
      enhanced fliA expression, but FleQ and RpoN were not necessary for basal
      expression. In addition, we identified the initiation site of fliA in L.
      pneumophila and found a putative sigma(70) promoter element localized upstream.
      The initiation site was not influenced in the DeltafleQ or DeltarpoN mutant
      strain. We demonstrated that there is no significant difference in the regulation
      of fliA between strains Corby and Paris, but the FleQ-dependent induction of fliA
      transcription in the exponential phase is stronger in strain Paris than in strain
      Corby. In addition, we showed for the first time the presence of a straight hook
      at the pole of the non-flagellated DeltafliA and DeltafliD mutant strains by
      electron microscopy, indicating the presence of an intact basal body in these
      strains.

PMID- 23011749
TI  - Roles of DNA repair and membrane integrity in heat resistance of Deinococcus
      radiodurans.
AB  - To study the effects of heat shock on Deinococcus radiodurans and the role of DNA
      repair in high temperature resistance, different strains of D. radiodurans (wild
      type, recA, irrE, and pprA) were treated with temperatures ranging from 40 to 100
      degrees C under wet and dry conditions. The mutant strains were more sensitive
      to wet heat of >=60  degrees C and dry heat of >=80  degrees C than the wild
      type. Both wild-type and DNA repair-deficient strains were much more resistant to
      high temperatures when exposed in the dried state as opposed to cells in
      suspension. Molecular staining techniques with the wild-type strain revealed that
      cells in the dried state were able to retain membrane integrity after drying and
      subsequent heat exposure, while heat-exposed cells in suspension showed
      significant loss of membrane integrity and respiration activity. The results
      suggest that the repair of DNA damage (e.g., DNA double-strand breaks by RecA and
      PprA) is essential after treatment with wet heat at temperatures >60  degrees C
      and dry heat >80  degrees C, and the ability of D. radiodurans to stabilize its
      plasma membrane during dehydration might represent one aspect in the protection
      of dried cells from heat-induced membrane damage.

PMID- 23011750
TI  - Postpartum trifecta: simultaneous eclamptic intracerebral hemorrhage, PRES, and
      herniation due to intracranial hypotension.
AB  - BACKGROUND: In the postpartum patient, sudden depression of consciousness may be
      caused by a number of etiologies and can result in serious consequences. Rapid,
      accurate diagnosis allows for specific treatments that optimize outcome, but
      diagnosis can be challenging in this population. We present a case of postpartum
      herniation due to intracranial hypotension in a patient with eclampsia, posterior
      reversible encephalopathy syndrome (PRES), and intracerebral hemorrhage (ICH).
      METHODS: Case report. RESULTS: A 26-year-old woman developed headache on
      postpartum day (PD) 1 after cesarean section with epidural anesthesia. Over the
      next 3 days, she developed progressively worsening headache and hypertension. On
      PD 5, she had a generalized seizure, leading to endotracheal intubation, propofol
      infusion, and transfer to our institution. By PD 6, she opened her eyes to voice,
      followed commands, moved all extremities, and had briskly reactive 4 mm pupils.
      MRI showed L parasagittal ICH with minimal mass effect, edema consistent with
      PRES, and brain descent with obliteration of the basal cisterns and tonsillar
      herniation. Later on PD 6, after diuresis for pulmonary edema, she became
      unresponsive with a dilated and nonreactive left pupil. She was laid flat for
      transport to CT, with improvement in arousal and pupil reactivity within 5 min.
      Intravascular volume was repleted with normal saline and albumin, and she was
      placed in the Trendelenburg position. Over the subsequent 8 h, she developed a
      dilated and nonreactive left pupil whenever her head was raised to horizontal.
      Her head position was gradually successfully raised over 48 h without need for a
      lumbar epidural blood patch. She was discharged home on PD 13 with only mild left
      arm dysmetria. CONCLUSIONS: Intracranial hypotension may coexist with other
      potential causes of cerebral herniation in the postpartum period. Establishing
      this diagnosis is crucial because its treatment is opposite that of other causes
      of herniation.

PMID- 23011751
TI  - Initial results of carotid artery stenting in Japan.
AB  - Carotid artery stenting (CAS) was approved by the government and reimbursement
      was started in 2008 in Japan, probably the last country in the world. CASCARD is
      a retrospective registry study performed by cardiologists to assess initial
      results of CAS in Japan. CAS was indicated for patients with at least one high
      risk factor for carotid endarterectomy and with >50 % stenosis in symptomatic or
      >80 % stenosis in asymptomatic patients. Primary endpoint was major adverse
      events (MAE) including death, myocardial infarction and any stroke at 30 days.
      Between April 2008 and March 2010, a total of 704 cases were enrolled from 55
      centers. The study population with an average age of 74 +/- 8 years included 62 %
      asymptomatic patients, with 23 % of cases with contralateral carotid artery
      occlusion or significant stenoses. Angioguard filter wire was exclusively used as
      a primary protection device and successfully passed the lesion in 701 cases (99.6
      %). Precise stent was implanted successfully in all cases. MAE at 30 days was
      3.7:0.3 % death, 0 % myocardial infarction, and 3.4 % stroke (0.4 % major
      ipsilateral stroke). Death or any stroke rate at 30 days was 2.7 % in
      asymptomatic and 5.5 % in symptomatic patients. The CASCARD study showed that the
      initial results of CAS in Japan are acceptable for both symptomatic and
      asymptomatic cases.

PMID- 23011752
TI  - Role of arterial stiffness and impaired renal function in the progression of new
      coronary lesions after percutaneous coronary intervention.
AB  - In the era of drug-eluting stents, revascularization of an initially non-target
      site owing to its progression as a new culprit lesion has emerged as a new
      therapeutic target of coronary artery disease. We aimed to clarify the prognostic
      factors for the progression of a previously non-significant coronary portion
      after prior percutaneous coronary intervention (PCI). We examined 275 patients
      who underwent PCI between February 2010 and January 2011 and had follow-up
      coronary angiography (CAG) after 6-12 months. Patients with target lesion
      revascularization were excluded. Finally, a total of 236 patients were included
      in this study. Thirty-three patients (14 %) underwent additional clinically
      driven PCI to treat previously non-significant lesions. There was no difference
      in background clinical characteristics between patients with and without
      additional PCI. The prevalence of chronic kidney disease (CKD; 61 vs. 31 %, p =
      0.001) and multivessel disease (MVD; 55 vs. 35 %, p = 0.027), and the brachial
      ankle pulse wave velocity (baPWV; 1,838 +/- 371 vs. 1,589 +/- 313 cm/s, p <
      0.001) were significantly higher in patients with additional PCI than in those
      without. A multivariate analysis showed that CKD, MVD, higher baPWV, and lower
      high-density lipoprotein cholesterol at the follow-up CAG were independent
      determinants of the progression of new culprit coronary lesions. In conclusion,
      higher baPWV, CKD, and MVD are independent predictors of later additional PCI,
      suggesting an important role for arterial stiffness and impaired renal function
      in the progression of new culprit coronary artery lesions after PCI.

PMID- 23011753
TI  - Validity of pediatric balance scales in children with spastic cerebral palsy.
AB  - This study was performed to examine the convergent and discriminant validity of
      the Pediatric Balance Scale (PBS), a modified version of the Berg Balance Scale
      (BBS), in children with spastic cerebral palsy (CP). A total of 38 children (age,
      4 to 10 years) with spastic CP who could ambulate participated in this study.
      PBS, equilibrium scores of Sensory Organization Test derived from computerized
      dynamic posturography, Gross Motor Function Measure (GMFM), and Pediatric
      Evaluation of Disability Inventory (PEDI) mobility skills were evaluated. With
      regard to convergent validity, PBS total score was moderately correlated with
      equilibrium score under the condition with eyes open, fixed foot support and
      condition with eyes closed, fixed foot support (rs = 0.579, eye open; rs = 0.448,
      eye closed; p < 0.05). PBS total score was highly correlated with GMFM scores
      (dimensions D and E; total GMFM-88; and GMFM-66) and capability, of the PEDI
      mobility domain, and moderately correlated with performance of the PEDI mobility
      domain. Discriminant validity indicated that PBS total score can distinguish
      between different Gross Motor Function Classification Scale levels in children
      with CP. PBS can be considered a simple, valid scale for examining functional
      balance capacity in children with spastic CP. Furthermore, it can better predict
      motor capacity and capability than equilibrium score and motor performance.

PMID- 23011754
TI  - Reverse micelles-mediated transport of lipase in liquid emulsion membrane for
      downstream processing.
AB  - This work deals with the downstream processing of lipase (EC 3.1.1.3, from
      Aspergillus niger) using liquid emulsion membrane (LEM) containing reverse
      micelles for the first time. The membrane phase consisted of surfactants
      [cetyltrimethylammonium bromide (CTAB) and Span 80] and cosolvents (isooctane and
      paraffin light oil). The various process parameters for the extraction of lipase
      from aqueous feed were optimized to maximize activity recovery and purification
      fold. The mechanism of lipase transport through LEM consisted of three steps
      namely solubilization of lipase in reverse micelles, transportation of reverse
      micelles loaded with lipase through the liquid membrane, and release of the
      lipase into internal aqueous phase. The results showed that the optimum
      conditions for activity recovery (78.6%) and purification (3.14-fold) were feed
      phase ionic strength 0.10 M NaCl and pH 9.0, surfactants concentration (Span 80
      0.18 M and CTAB 0.1 M), volume ratio of organic phase to internal aqueous phase
      0.9, ratio of membrane emulsion to feed volume 1.0, internal aqueous phase
      concentration 1.0 M KCl and pH 7.0, stirring speed 450 rpm, and contact time 15
      min. This work indicated the feasibility of LEM for the downstream processing of
      lipase.

PMID- 23011755
TI  - The thiolate-catalyzed intermolecular crossed Tishchenko reaction: highly
      chemoselective coupling of two different aromatic aldehydes.

PMID- 23011756
TI  - Could progressive iron loss from mucosal microbleeding represent a mechanism of
      cancer prevention from prolonged aspirin use?

PMID- 23011757
TI  - Reaginic antibodies from horses with recurrent airway obstruction produce mast
      cell stimulation.
AB  - Reaginic antibodies (IgE and some IgG subclasses) and mast cells play important
      roles in the induction of type I immediate hypersensitivity reactions. These
      antibodies bind through their Fc fragment to high affinity receptors
      (FcepsilonRI) present in the membrane of mast cells and basophils. The cross
      linking of the receptor initiates a coordinated sequence of biochemical and
      morphological events that results in exocytosis of secretory granules containing
      pre-formed inflammatory mediators, secretion of newly formed lipid mediators, and
      secretion of cytokines. Previously, several studies have investigated the role of
      reaginic antibodies in the pathogenesis of Recurrent Airway Obstruction (RAO).
      However, whereas the immunological aspects of RAO have been extensively studied,
      the precise sequence of events involved in the pathogenesis remains not
      completely understood, and the role of IgE in this disease remains controversial.
      Therefore, in this study, several bioassays were conducted to determine whether
      reaginic antibodies from RAO-affected horses have the ability to activate mast
      cells. These bioassays involved measuring degranulation of rat peritoneal mast
      cells, activation of NF-kappaB and morphological changes in basophilic leukemia
      cells (RBL-2H3) following incubation with horse serum from RAO-affected horses
      that were sensitive and insensitive to Aspergillus fumigatus (A. fumigatus) or
      from unaffected horses. Our results show that reaginic antibodies from horses
      sensitive to A. fumigatus were able to degranulate rat peritoneal mast cells. In
      additon, there was an increase in the activity of the transcription factor NF
      kappaB in RBL-2H3 cells, and morphological changes were observed in these cells
      once cross-linking was produced. These findings were not found in horses not
      sensitive to A. fumigatus and healthy horses. These bioassays demonstrate the
      ability of reaginic antibodies to stimulate mast cells and indicate that these
      antibodies could be involved in the immunological mechanisms leading to RAO.

PMID- 23011758
TI  - HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site
      antagonism.
AB  - Despite advances in HIV therapy, viral resistance and side-effects with current
      drug regimens require targeting new components of the virus. Dual antagonist
      peptide triazoles (PT) are a novel class of HIV-1 inhibitors that specifically
      target the gp120 component of the viral spike and inhibit its interaction with
      both of its cell surface protein ligands, namely the initial receptor CD4 and the
      co-receptor (CCR5/CXCR4), thus preventing viral entry. Following an initial
      survey of 19 gp120 alanine mutants by ELISA, we screened 11 mutants for their
      importance in binding to, and inhibition by the PT KR21 using surface plasmon
      resonance. Key mutants were purified and tested for their effects on the
      peptide's affinity and its ability to inhibit binding of CD4 and the co-receptor
      surrogate mAb 17b. Effects of the mutations on KR21 viral neutralization were
      measured by single-round cell infection assays. Two mutations, D474A and T257A,
      caused large-scale loss of KR21 binding, as well as losses in both CD4/17b and
      viral inhibition by KR21. A set of other Ala mutants revealed more moderate
      losses in direct binding affinity and inhibition sensitivity to KR21. The cluster
      of sensitive residues defines a PT functional epitope. This site is in a
      conserved region of gp120 that overlaps the CD4 binding site and is distant from
      the co-receptor/17b binding site, suggesting an allosteric mode of inhibition for
      the latter. The arrangement and sequence conservation of the residues in the
      functional epitope explain the breadth of antiviral activity, and improve the
      potential for rational inhibitor development.

PMID- 23011760
TI  - T2* MRI of minimal hepatic encephalopathy and cognitive correlates in vivo.
AB  - PURPOSE: To evaluate regional brain iron deposition in minimal hepatic
      encephalopathy (MHE) patients using T2*-weighted gradient-echo imaging and to
      explore the relationship between T2* MR changes and cognitive performance.
      MATERIALS AND METHODS: Forty hepatitis-B virus (HBV)-related cirrhotic patients
      and 22 age-, sex-, and education-matched healthy controls were included in this
      study. Of the patients, twenty eight patients were diagnosed with MHE. All
      subjects were administered Number Connection Test-A (NCT-A), Letter Digit
      Substitution Test (LDST), Rey-Osterrieth Complex Figure Test (RCFT), and the Mini
      Mental State Examination (MMSE). T2*-weighted gradient-echo images were acquired
      using 3 Tesla MRI. Phase values (putative iron levels) in the frontal-basal
      ganglia-thalamocortical circuits were measured. Spearman correlation and multiple
      linear regression analysis were performed. RESULTS: MHE patients exhibited
      significantly prolonged NCT-A time and decreased LDST, RCFT immediate and delayed
      recall scores. Significant decreases of phase values in the bilateral putamen
      were detected in MHE patients compared to without MHE patients and controls.
      Multiple linear regression analysis confirmed significant correlations between
      the phase values in the putamen and right frontal white matter and cognitive
      performances by MHE patients. CONCLUSION: Decreased phase values in the frontal
      cortical-basal ganglial circuits independently contribute to cognitive
      impairments in MHE patients.

PMID- 23011759
TI  - Carboxylesterases are uniquely expressed among tissues and regulated by nuclear
      hormone receptors in the mouse.
AB  - Carboxylesterases (CES) are a well recognized, yet incompletely characterized
      family of proteins that catalyze neutral lipid hydrolysis. Some CES have well
      defined roles in xenobiotic clearance, pharmacologic prodrug activation, and
      narcotic detoxification. In addition, emerging evidence suggests other CES may
      have roles in lipid metabolism. Humans have six CES genes, whereas mice have 20
      Ces genes grouped into five isoenzyme classes. Perhaps due to the high sequence
      similarity shared by the mouse Ces genes, the tissue-specific distribution of
      expression for these enzymes has not been fully addressed. Therefore, we
      performed studies to provide a comprehensive tissue distribution analysis of
      mouse Ces mRNAs. These data demonstrated that while the mouse Ces family 1 is
      highly expressed in liver and family 2 in intestine, many Ces genes have a wide
      and unique tissue distribution defined by relative mRNA levels. Furthermore,
      evaluating Ces gene expression in response to pharmacologic activation of lipid-
      and xenobiotic-sensing nuclear hormone receptors showed differential regulation.
      Finally, specific shifts in Ces gene expression were seen in peritoneal
      macrophages following lipopolysaccharide treatment and in a steatotic liver model
      induced by high-fat feeding, two model systems relevant to disease. Overall these
      data show that each mouse Ces gene has its own distinctive tissue expression
      pattern and suggest that some CES may have tissue-specific roles in lipid
      metabolism and xenobiotic clearance.

PMID- 23011761
TI  - Imaging pain in arthritis: advances in structural and functional neuroimaging.
AB  - Arthritis is a heterogeneous disease characterized by joint stiffness, swelling,
      and pain. Although primarily considered a peripheral joint disease, the severity
      of pain reported by arthritis patients does not always reflect the extent of
      joint pathology detectable by conventional means. Using structural and functional
      brain imaging techniques, a growing number of evolving neuroimaging methods are
      providing insight into these observed discrepancies at different time-scales. Of
      these methods, functional magnetic resonance imaging is exploited for short-term
      evoked pain examination and treatment evaluation; 'resting-state' approaches
      provide insight into fluctuations in pain; perfusion imaging captures elements of
      on-going clinical pain; and morphological brain assessment provides evidence for
      long-term structural changes in the brain associated with chronic pain. Further
      insight into arthritic pain processing at the brain-systems level could in the
      future be provided by combined neuroimaging approaches, specifically
      investigating the interactions between functional and structural alterations.

PMID- 23011762
TI  - Plasma human neutrophil proteins-1, -2, and -3 levels in patients with bladder
      cancer.
AB  - OBJECTIVES: Human neutrophil proteins-1, -2, and -3 (HNPs -1, -2, and -3) are
      expressed in several tumor types. However, the role of HNPs 1-3 in human bladder
      cancer has not yet been determined. We investigated the association between the
      plasma levels of HNPs 1-3 and clinicopathological parameters in bladder cancer
      patients. DESIGN AND METHODS: The plasma levels of HNPs 1-3 were measured in 60
      patients with bladder cancer and in 58 healthy controls. The plasma levels of
      HNPs 1-3 were determined by a solid-phase enzyme-linked immunosorbent assay
      (ELISA). Plasma samples were obtained before surgery. Plasma samples were
      permitted to clot and were then stored at -80  degrees C until use. RESULTS: The
      levels of the HNPs increased from grade 1 to 4 tumors and this difference was
      statistically significant (p < 0.001). Additionally, plasma HNP levels were
      significantly higher in patients with metastatic bladder cancer and in patients
      with lymphovascular involvement, metastasis of the lymph nodes, and increased
      tumor burden (p < 0.001). CONCLUSIONS: The preoperative plasma levels of HNPs 1-3
      paralleled the progression and pathological stages of the malignancies. This
      study suggests that HNPs 1-3 promote tumor invasion and are potential indicators
      of disease progression in patients with bladder cancer.

PMID- 23011764
TI  - Enhancing the light harvesting capability of a photosynthetic reaction center by
      a tailored molecular fluorophore.
AB  - Light machine: The simplest photosynthetic protein able to convert sunlight into
      other energy forms is covalently functionalized with a tailored organic dye to
      obtain a fully functional hybrid complex that outperforms the natural system in
      light harvesting and conversion ability.

PMID- 23011763
TI  - Prognostic value of ERCC1 in head and neck carcinoma treated with definitive or
      adjuvant radiotherapy.
AB  - PURPOSE: To evaluate the prognostic significance of excision repair cross
      complementation group 1 (ERCC1) expression in head and neck carcinoma patients
      treated with definitive radiotherapy (DR) or adjuvant radiotherapy (AR). METHODS:
      ERCC1 expression was assessed by immunohistochemical staining. A total of 48
      patients were assessed. RESULTS: High ERCC1 expression was found in 23 patients
      (48 %). More ERCC1-positive tumours were detected in patients treated with DR
      than in patients treated with AR (73 vs. 36 %, respectively, p = 0.03). ERCC1
      expression had no impact on overall survival neither in the whole cohort of
      patients (p = 0.16) nor in each particular treatment group (AR p = 0.98; DR p =
      0.21). CONCLUSIONS: ERCC1 expression had no predictive value in head and neck
      carcinoma patients treated with DR or AR. There might be difference in ERCC1
      positivity that comes out of whether the assessment is done on biopsy or surgical
      specimens.

PMID- 23011765
TI  - Expression of R132H mutational IDH1 in human U87 glioblastoma cells affects the
      SREBP1a pathway and induces cellular proliferation.
AB  - Sterol regulatory element-binding protein-1a (SREBP1a) is a member of the SREBP
      family of transcription factors, which mainly controls homeostasis of lipids.
      SREBP1a can also activate the transcription of isocitrate dehydrogenase 1 (IDH1)
      by binding to its promoter region. IDH1 mutations, especially R132H mutation of
      IDH1, are a common feature of a major subset of human gliomas. There are few data
      available on the relationship between mutational IDH1 expression and SREBP1a
      pathway. In this study, we investigated cellular effects and SREBP1a pathway
      alterations caused by R132H mutational IDH1 expression in U87 cells. Two glioma
      cell lines, stably expressing mutational (U87/R132H) or wild type (U87/wt) IDH1,
      were established. A cell line, stably transfected with pcDNA3.1(+) (U87/vector),
      was generated as a control. Click-iT EdU assay, sulforhodamine B assay, and wound
      healing assay respectively showed that the expression of R132H induced cellular
      proliferation, cell growth, and cell migration. Western blot revealed that SREBP1
      was increased in U87/R132H compared with that in U87/wt. Elevated SREBP1a and
      several its target genes, but not SREBP1c, were detected by real-time polymerase
      chain reaction in U87/R132H. All these findings indicated that R132H mutational
      IDH1 is involved in the regulation of proliferation, growth, and migration of
      glioma cells. These effects may partially be mediated by SREBP1a pathway.

PMID- 23011767
TI  - Application of aurintricarboxylic acid for the adherence of mouse P19 neurons and
      primary hippocampal neurons to noncoated surface in serum-free culture.
AB  - Dissociated primary neuron culture has been the most widely used model systems
      for neuroscience research. Most of these primary neurons are cultured on adhesion
      matrix-coated surface to provide a proper environment for cell anchorage under
      serum-free conditions. In this study, we provide an alternative technique to
      promote the adhesions of these neurons using aurintricarboxylic acid (ATA), a
      nonpeptide compound, without surface manipulations. We first demonstrated that
      ATA could promote Chinese hamster ovary cell attachment and proliferation in
      serum-free medium in a dosage-dependent manner. We later showed that ATA
      significantly enhanced the attachment of the retinoic acid differentiated P19
      mouse embryonal carcinoma (P19) neurons, with an optimal concentration around 30
      MUg/mL. A similar result was seen in primary hippocampal neurons, with an optimal
      ATA concentration around 15 MUg/mL. Further morphological assessments revealed
      that the average neurite length and neuronal polarization were almost identical
      to that obtained using a conventional method with poly-L-lysine surface. The
      advantages of using the ATA treatment technique for immunochemical analysis are
      discussed.

PMID- 23011768
TI  - [Number of patients with chronic dyspnea in three German specialist practices].
AB  - In the second quarter 2011 the incidence of the symptoms "chronic dyspnea" among
      the patients in three specialist practices was determined by means of a self
      developed questionnaire. 1286 anonymised questionnaires with full information
      could be evaluated. The proportion of the patients with a chronic dyspnea
      (inclusive "dyspnea and weakness feeling") in the practices amounted to between
      15.3 and 57.7 %. An exclusive assessment of chronic dyspnea could be assigned to
      10.4 to 31.4 % of the patients evaluated. From the view point of the treating
      physicians, the cause of the chronic dyspnea was sufficiently explained by the
      available information.

PMID- 23011766
TI  - Hormonal control of Sertoli cell metabolism regulates spermatogenesis.
AB  - Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have
      functions that reach far beyond the physical support of germ cells, as they are
      responsible for creating the adequate ionic and metabolic environment for germ
      cell development. Thus, much attention has been given to the metabolic
      functioning of SCs. During spermatogenesis, germ cells are provided with suitable
      metabolic substrates, in a set of events mediated by SCs. Multiple signaling
      cascades regulate SC function and several of these signaling pathways are hormone
      dependent and cell-specific. Within the seminiferous tubules, only SCs possess
      receptors for some hormones rendering them major targets for the hormonal
      signaling that regulates spermatogenesis. Although the mechanisms by which SCs
      fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC
      metabolism is unquestionably a regulation point for germ cell development and the
      hormonal control of these processes is required for a normal spermatogenesis.

PMID- 23011769
TI  - [Multiple myeloma as a rare cause of a pancoast tumor].

PMID- 23011770
TI  - [Obstructive sleep apnoea and oxidative stress].
AB  - BACKGROUND: Untreated obstructive sleep apnoea (OSA) is characterised by elevated
      systemic and local oxidative stress and inflammation. Non-invasive measurement of
      metabolites and markers of inflammation in exhaled breath condensate (EBC) is of
      interest in the interpretation of systemic effects of severe obstructive sleep
      apnoea. In patients with severe sleep apnoea (AHI >= 30 /h) we investigated if
      CPAP therapy with normalisation of AHI induces changes of H2O2 concentrations in
      EBC. MATERIAL AND METHODS: Patients with obstructive sleep apnea (AHI >= 30 /h)
      had H2O2 analysis of EBC after native PSG, after the first night and after 6
      weeks of CPAP therapy. Only patients with normalisation of AHI (AHI <= 10  /h)
      were included in the further analysis. RESULTS: 23 patients (21 men and 2 women)
      fulfilled the inclusion criteria. The first night of CPAP therapy led to a
      significant reduction of AHI, but did not change the H2O2 concentration in EBC.
      After 6 weeks of CPAP therapy with normalisation of AHI (3 +/- 3 /h) H2O2 in EBC
      showed a significant reduction from 450 +/- 163 nmol/L to 294 +/- 110 nmol/L.
      Subgroup analysis showed that in non-smokers and especially in smokers the
      reduction was less marked than in ex-smokers. CONCLUSION: Normalisation of AHI
      after 6 weeks of CPAP therapy in OSA induces a significant reduction of H2O2 in
      EBC. This primarily represents a reduction of local inflammation and oxidative
      stress in the airways, but also indicates a positive effect on elevated oxidative
      stress in OSA. The influence of smoking status needs further investigations,
      including subgroup analysis with a sufficient number of patients.

PMID- 23011771
TI  - [Early treatment of COPD with tiotropium].
AB  - BACKGROUND: In a prespecified subgroup analysis of the 4-year trial
      "Understanding Potential Long-term Impacts on Function with Tiotropium", the
      efficacy of tiotropium versus control in patients with moderate COPD (GOLD II)
      was examined and compared with the pooled results of patients with more severe
      disease (GOLD III/IV). METHODS: Randomised, multicentre, double-blind, placebo
      controlled, parallel-group study in 5993 patients over a period of 4 years.
      Patients received either tiotropium 18 ug or placebo once-daily. The study
      endpoints were the annual FEV1 decline as well as lung function parameters,
      health status, exacerbations and all-cause mortality. RESULTS: 46 % of the
      patients had moderate disease (GOLD II; tiotropium: n = 1384, control group: n =
      1355) with a mean postbronchodilator FEV1 of 1.63 (0.37) L (59 % predicted). In
      these patients with moderate COPD, tiotropium significantly improved the absolute
      FEV1 values (pre-bronchodilator FEV1: 101 - 119 ml, post-bronchodilator FEV1: 52 
      82 ml, p < 0.001) and the postbronchodilator FEV1 decline compared with the
      control patients (43 (2) vs. 49 (2) ml/year; p = 0.024). In addition, there was a
      statistically significant improvement in the annual exacerbation rate
      (tiotropium: 0.56, control: 0.7; p < 0.0001), the time to first exacerbation
      (tiotropium: 23.09, control: 17.47 months; p < 0.0001) and health status
      (tiotropium vs. control: minus 2.7 - 4 units; p < 0.0001) in the tiotropium
      group.  CONCLUSIONS: The results of this subgroup analysis support current
      guideline recommendations and indicate that already patients with moderate COPD
      (GOLD stage II) benefit clinically from treatment with tiotropium.

PMID- 23011772
TI  - Author's reply to Kapoor S. GTP cyclohydrolase and cancer pain.

PMID- 23011773
TI  - Self-healing microencapsulation of biomacromolecules without organic solvents.

PMID- 23011775
TI  - Complete nucleotide sequence of a Chinese isolate of Grapevine leafroll
      associated virus 3 reveals a 5' UTR of 802 nucleotides.
AB  - Grapevine leafroll-associated virus 3 (GLRaV-3) is widely spread in China. Here
      we report, for the first time, the complete nucleotide sequence of the Chinese
      isolate (LN) of GLRaV-3. The 18,563-nt genomic RNA is the largest of the GLRaV-3
      genomes reported to date, with a 5' untranslated region of 802 nt. Its sequence
      shares 87.99-98.15 % identity with those of previously reported isolates, and
      phylogenetic analysis suggested placing isolate LN in group 3, together with
      another fully sequenced isolate, PL-20.

PMID- 23011774
TI  - Phylogenetic analysis of Bombyx mori nucleopolyhedrovirus polyhedrin and p10
      genes in wild isolates from Guangxi Zhuang Autonomous Region, China.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) is a severe pathogen that seriously
      impacts the sericulture industry. In this study, 45 wild BmNPV isolates were
      collected from different silkworm-raising regions in China's Guangxi Zhuang
      Autonomous Region. Two highly expressed very late genes from each isolate,
      polyhedrin and p10, were sequenced and subjected to phylogenetic analysis. The
      polyhedrin gene was found to be highly conserved, while the p10 gene was more
      variable frequently harboring point mutations and displaying variations in codon
      use without obvious codon bias. The BmNPV isolates from Guangxi were separated
      into three main clades, I, II, and III, according to the p10 gene phylogenetic
      tree. The geographical distribution of clade I isolates in Guangxi showed a
      concentrated pattern and that of clade II isolates showed a connected pattern.
      Clade III isolates were irregularly scattered throughout Guangxi. Local
      transmission of this pathogen clearly occurred in the silkworm-raising regions in
      Guangxi. This study may provide some data on BmNPV transmission in the silkworm
      raising regions and be helpful in devising strategies for the prevention and
      control of BmNPV disease.

PMID- 23011776
TI  - Molecular characterization of influenza B viruses isolated in east-central China
      in 2009-2010.
AB  - The current circulating influenza B viruses can be divided into two major
      phylogenetic lineages: the Victoria and Yamagata lineages. We conducted a survey
      of influenza B viruses in Hubei and Zhejiang provinces during 2009-2010. Out of
      341 throat swabs, 18 influenza B viruses were isolated. Five isolates were
      selected for genetic and phylogenetic analysis. The molecular analyses revealed
      that all the isolates had similar antigenic characteristics to
      B/Brisbane/60/2008. However, in the three viruses isolated from Zhejiang, a
      single asparagine to aspartic acid substitution in position 197 was observed,
      thereby eliminating the glycosylation at that site and possibly causing an
      antigenic change. None of the viruses had amino acid mutations at positions 116,
      149, 152, 198, 222, 250, 291, and 402 of the neuraminidase (NA) gene, predicting
      that the viruses would still be sensitive to NA inhibitors. Phylogenetic analyses
      revealed that all five isolates were closely related to B/Brisbane/60/2008-the
      2010 vaccine strain-and contained Victoria-like hemagglutinin and Yamagata-like
      NA genes, suggesting that reassortment may had occurred. In addition, similar
      phylogenetic patterns among the acidic polymerase, nucleoprotein and matrix
      protein genes, as well as between the basic polymerase 1 and basic polymerase 2
      genes, were observed, suggesting possible functional interactions among these
      proteins. All the results highlighted the importance of molecular monitoring of
      influenza B viruses for reassortment and antigenic drift.

PMID- 23011777
TI  - Molecular characterization of Indian sugarcane streak mosaic virus isolate.
AB  - Sugarcane streak mosaic virus (SCSMV), a member of the genus Poacevirus, family
      Potyviridae, is an important viral pathogen affecting sugarcane cultivation in
      India. The complete nucleotide sequence of a SCSMV isolate from India (SCSMV-IND)
      was determined. The linear, assembled, single-stranded positive-sense RNA genome
      of SCSMV-IND was 9,786 nucleotides in length (excluding the poly (A) tail) and
      encoded a polyprotein of 3,131 amino acid residues. The genome of SCSMV-IND
      shared high degree of sequence identity with SCSMV-PAK (93 % at nucleotide and 97
      % at amino acid), and shared only 81 % nucleotide and 94 % amino acid identities
      with all the four SCSMV isolates (SCSMV-JP1, -JP2, -ID, and -THA). Phylogenetic
      tree analysis of the complete genome sequences of SCSMV isolates revealed that
      they can be clustered into two groups. SCSMV-IND and -AP isolates showed 18 %
      (nucleotide) divergence within the highly conserved 3' partial genome, suggesting
      a high level of genetic diversity among the Indian SCSMV isolates.

PMID- 23011778
TI  - The translocation kinetics of antibiotics through porin OmpC: insights from
      structure-based solvation mapping using WaterMap.
AB  - Poor permeability of the lipopolysaccharide-based outer membrane of Gram-negative
      bacteria is compensated by the existence of protein channels (porins) that
      selectively admit low molecular weight substrates, including many antibiotics.
      Improved understanding of the translocation mechanisms of porin substrates could
      help guide the design of antibiotics capable of achieving high intracellular
      exposure. Energy barriers to channel entry and exit govern antibiotic fluxes
      through porins. We have previously reported a hypothesis that the costs of
      transferring protein solvation to and from bulk medium underlie the barriers to
      protein-ligand association and dissociation, respectively, concomitant with the
      gain and loss of protein-ligand interactions during those processes. We have now
      applied this hypothesis to explain the published rates of entry (association) and
      exit (dissociation) of six antibiotics to/from reconstituted E. coli porin OmpC.
      WaterMap was used to estimate the total water transfer energies resulting from
      transient occupation by each antibiotic. Our results suggest that solvation
      within the porin cavity is highly energetically favorable, and the observed
      moderately fast entry rates of the antibiotics are consistent with replacement of
      protein-water H-bonds. The observed ultrafast exit kinetics is consistent with
      the lack of intrachannel solvation sites that convey unfavorable resolvation
      during antibiotic dissociation. These results are aligned with known general
      relationships between antibiotic efficacy and physicochemical properties, namely
      unusually low logP, reflecting an abundance of H-bond partners. We conclude that
      antibiotics figuratively "melt" their way through porin solvation at a rate
      determined by the cost of exchanging protein-solvent for protein-antibiotic H
      bonds.

PMID- 23011779
TI  - Hypercalcemia induces a proinflammatory phenotype in rat leukocytes and
      endothelial cells.
AB  - Endothelial plasma membrane lipid microdomains, so called lipid rafts/caveolae,
      are rich in neutral glycosphingolipid, globotriaosylceramide, Gb3Cer, or CD77.
      Several plasma membrane Ca(2+) channels and pumps are located in lipid
      rafts/caveolae. Increased Ca(2+) influx could cause the development of an
      endothelial proinflammatory phenotype. Therefore, the aim of this study was to
      estimate the effects of hypercalcemia in rats by determination of CD77 expression
      on CD34+ endothelial cells in the heart, kidney, and vena cava. In addition,
      potential proinflammatory calcium effect was estimated by CD11b and CD15s
      expression on leukocytes. To achieve hypercalcemia, Sprague-Dawley male rats were
      given CaCl2 solution with a concentration of 1.5 % elemental calcium during 14
      days. CD77 expression on CD34+ endothelial cells in cell suspensions of the
      heart, kidney, and vena cava, as well as leukocyte expression of CD11b and CD15s
      in hypercalcemic and control rats were determined by flow cytometry. Ionized
      calcium concentration in plasma was 1.37 +/- 0.01 mM in hypercalcemic vs. 1.19 +/
      0.03 mM in control rats. Hypercalcemic group showed statistically significantly
      decreased proportion of endothelial CD34+ CD77- cells in the kidney and vena cava
      in parallel with increase of CD11b and CD15s leukocyte proinflammatory markers.
      In conclusion, it is tempting to speculate that plasma membranes of
      glycosphingolipid CD77- endothelial cells are poorer in caveolae lipid
      microdomains and therefore weaker in controlling of Ca(2+) influx. The percentage
      of CD11b+ CD15s+ leukocytes could be a measure of proinflammatory effects of mild
      hypercalcemia.

PMID- 23011780
TI  - Mechanisms associated to impaired activity of cardiac P-type ATPases in
      endothelial nitric oxide synthase knockout mice.
AB  - The effect of long-lasting in vivo restriction of nitric oxide (NO)
      bioavailability on cardiac and renal P-type ATPases critical for intracellular
      ion homeostasis is controversial. Previous work has shown in eNOS knockout (eNOS(
      /-)) mice hearts that Na(+)/K(+)- and Ca(2+)-ATPase activities were depressed but
      the underlying mechanisms are still unclear. The goal of this study was to
      characterize potential alterations responsible for impaired enzyme activity in
      eNOS(-/-) mice. Na(+)/K(+)-ATPase activity from crude preparations of adult male
      eNOS(-/-) mice hearts and kidneys was reduced compared with wild-type animals (32
      %, p < 0.05 and 16 %, p < 0.0001, respectively). Immunoblot analysis showed that
      although the expression of the predominant (or exclusive, for the kidney)
      Na(+)/K(+)-ATPase alpha1 isoform was not significantly changed, there was an
      important downregulation of the less abundant alpha2 isoform in the heart (57 %,
      p < 0.0001). In addition, although cardiac Ca(2+)-ATPase activity was unaltered,
      the expression of sarco/endoplasmic reticulum Ca(2+)-ATPase 2 protein in eNOS(-/
      ) mice was very high (290 % compared with wild-type animals, p < 0.0001) without
      any significant change in phospholamban expression. Consistent with these
      findings, the content of cardiac and renal free sulfhydryl groups, essential for
      the catalytic function of such ATPases, was decreased (23 %, p < 0.01 and 35 %, p
      < 0.05, respectively). Altogether, the present results suggest that the absence
      of eNOS promotes a compartmentalized altered redox balance that affects the
      activity and expression of ion transport ATPases.

PMID- 23011781
TI  - Endurance training in mice increases the unfolded protein response induced by a
      high-fat diet.
AB  - Certain conditions, such as several weeks of high-fat diet, disrupt endoplasmic
      reticulum (ER) homeostasis and activate an adaptive pathway referred as the
      unfolded protein response. When the unfolded protein response fails, the result
      is the development of inflammation and insulin resistance. These two pathological
      states are known to be improved by regular exercise training but the mechanisms
      remain largely undetermined. As it has recently been shown that the unfolded
      protein response is regulated by exercise, we hypothesised that concomitant
      treadmill exercise training (HFD+ex) prevents ER homeostasis disruption and its
      downstream consequences induced by a 6-week high-fat diet (HFD) in mice by
      activating the protective unfolded protein response. Several well-documented
      markers of the unfolded protein response were measured in the soleus and tibialis
      anterior muscles as well as in the liver and pancreas. In HFD mice, an increase
      in these markers was observed (from 2- to 15-fold, P < 0.05) in all tissues
      studied. The combination of HFD+ex increased the expression of several markers
      further, up to 100 % compared to HFD alone (P < 0.05). HFD increased inflammatory
      markers both in the plasma (IL-6 protein, 2.5 +/- 0.52-fold; MIP-1alpha protein,
      1.3 +/- 0.13-fold; P < 0.05) and in the tissues studied, and treadmill exercise
      attenuated the inflammatory state induced by HFD (P < 0.05). However, treadmill
      exercise could not reverse HFD-induced whole body glucose intolerance, assessed
      by OGTT (AUC, 1.8 +/- 0.29-fold, P < 0.05). In conclusion, our results show that
      a HFD activated the unfolded protein response in mouse tissues in vivo, and that
      endurance training promoted this response. We speculate that the potentiation of
      the unfolded protein response by endurance training may represent a positive
      adaptation protecting against further cellular stress.

PMID- 23011782
TI  - Effect of tetrahydrobiopterin and exercise training on endothelium-dependent
      vasorelaxation in SHR.
AB  - We examined whether the improvement of impaired NO-dependent vasorelaxation by
      exercise training could be mediated through a BH4-dependent mechanism. Male
      spontaneously hypertensive rats (SHR, n = 20) and Wistar-Kyoto rats (WKY, n = 20)
      were trained (Tr) for 9 weeks on a treadmill and compared to age-matched
      sedentary animals (Sed). Endothelium-dependent vasorelaxation (EDV) was assessed
      with acetylcholine by measuring isometric tension in rings of femoral artery
      precontracted with 10(-5) M phenylephrine. EDV was impaired in SHR-Sed as
      compared to WKY-Sed (p = 0.02). Training alone improved EDV in both WKY (p =
      0.01) and SHR (p = 0.0001). Moreover, EDV was not different in trained SHR than
      in trained WKY (p = 0.934). Pretreatment of rings with L-NAME (50 MUM) cancelled
      the difference in ACh-induced relaxation between all groups, suggesting that NO
      pathway is involved in these differences. The presence of 10(-5) M BH4 in the
      organ bath significantly improved EDV for sedentary SHR (p = 0.030) but not WKY
      group (p = 0.815). Exercise training turned the beneficial effect of BH4 on SHR
      to impairment of ACh-induced vasorelaxation in both SHR-Tr (p = 0.01) and WKY-Tr
      groups (p = 0.04). These results suggest that beneficial effect of exercise
      training on endothelial function is due partly to a BH4-dependent mechanism in
      established hypertension.

PMID- 23011783
TI  - Reassessing the folding of the KIX domain: evidence for a two-state mechanism.
AB  - The debate about the presence and role of intermediates in the folding of
      proteins has been a critical issue, especially for fast folders. One of the
      classical methodologies to identify such metastable species is the "burst-phase
      analysis," whereby the observed signal amplitude from stopped-flow traces is
      determined as a function of denaturant concentration. However, a complication may
      arise when folding is sufficiently fast to jeopardize the reliability of the
      stopped-flow technique. In this study, we reassessed the folding of the KIX
      domain from cAMP Response Element-Binding (CREB)-binding protein, which has been
      proposed to involve the formation of an intermediate that accumulates in the dead
      time of the stopped flow. By using an in-house-built capillary continuous flow
      with a 50-MUs dead time, we demonstrate that this intermediate is not present;
      the problem arose because of the instrumental limitation of the standard stopped
      flow to assess very fast refolding rate constants (e.g., >= 500 s-1).

PMID- 23011784
TI  - Association between survival in patients with primary invasive breast cancer and
      computer aided MRI.
AB  - PURPOSE: To identify the potential of semi-quantitative enhancement-analysis in
      breast MRI to predict disease-related death in primary breast cancer patients.
      MATERIALS AND METHODS: The present study was planned and conducted according to
      international recommendations. All patients referred for pretherapeutic staging
      of primary breast cancer during 24 consecutive months were included into the
      study collective. They were followed-up by our multidisciplinary breast center.
      For semi-quantitative MRI-analysis dedicated CAD-software (computer assisted
      diagnosis) was used. Association between enhancement parameters and disease
      related survival was investigated using Cox proportional-hazards -regression
      (CR). RESULTS: A total of 115 patients were eligible for CR analysis. Median
      follow-up time was 52 months. In 15 patients, disease-related death occurred. CR
      analysis identified four enhancement parameters as independent and significant (P
      < 0.001) predictors of the endpoint. Coefficients were "Initial enhancement" (B =
      0.0166), "Time to peak-enhancement" (B = 1.0573), "Tumor volume" (B = 0.0175),
      and proportion of "tumor volume" showing "slow initial enhancement" followed by a
      "persistent" curve-type (B = -0.0586). CONCLUSION: This study demonstrates the
      significant relationship between semi-quantitative enhancement analysis in breast
      MRI and disease-related death of breast cancer patients. As results were
      extracted from a routine staging examination, MRI noninvasively provides not only
      diagnostic information but also outcome data at one step. Future studies should
      address the impact of these findings on patient management and therapeutic
      approach.

PMID- 23011785
TI  - Treatment of childhood sexual abuse: an updated review.
AB  - Childhood sexual abuse (CSA) involves multiple complex factors that make the
      evaluation of therapeutic interventions especially complicated. PTSD prevalence
      rates of CSA are approximately 37 % -53 %. Several other psychiatric sequelae of
      CSA exist. CSA appears to disrupt brain and body physiology. One co-located
      service delivery model reported a 52 % linkage rate of CSA survivors with mental
      health treatment. This article reviews current literature on the treatment of
      CSA, including psychosocial interventions, pharmacotherapy, and early
      preventative interventions. It also provides an update on the short- and long
      term sequelae of CSA and implications for future research directions. A
      literature search of papers published in the last 3 years was conducted using the
      keywords treatment, sexual abuse, childhood, epigenetics, resilience and review,
      and searching the following databases: PsycInfo, PubMed, Substance Abuse and
      Mental Health Services Administration, and Centers for Disease Control.

PMID- 23011786
TI  - The complexities of depression.

PMID- 23011787
TI  - Review of experimental and quasi-experimental studies finds that mindfulness
      based interventions are more effective than standard care for reducing depressive
      symptoms in adults with mental disorders.

PMID- 23011788
TI  - Single mutation in Shine-Dalgarno-like sequence present in the amino terminal of
      lactate dehydrogenase of Plasmodium effects the production of an eukaryotic
      protein expressed in a prokaryotic system.
AB  - One of the most important step in structure-based drug design studies is
      obtaining the protein in active form after cloning the target gene. In one of our
      previous study, it was determined that an internal Shine-Dalgarno-like sequence
      present just before the third methionine at N-terminus of wild type lactate
      dehydrogenase enzyme of Plasmodium falciparum prevent the translation of full
      length protein. Inspection of the same region in P. vivax LDH, which was
      overproduced as an active enzyme, indicated that the codon preference in the same
      region was slightly different than the codon preference of wild type PfLDH. In
      this study, 5'-GGAGGC-3' sequence of P. vivax that codes for two glycine residues
      just before the third methionine was exchanged to 5'-GGAGGA-3', by mimicking P.
      falciparum LDH, to prove the possible effects of having an internal SD-like
      sequence when expressing an eukaryotic protein in a prokaryotic system. Exchange
      was made by site-directed mutagenesis. Results indicated that having two glycine
      residues with an internal SD-like sequence (GGAGGA) just before the third
      methionine abolishes the enzyme activity due to the preference of the prokaryotic
      system used for the expression. This study emphasizes the awareness of use of a
      prokaryotic system to overproduce an eukaryotic protein.

PMID- 23011789
TI  - Molecular cloning and characterization of glutamine synthetase, a tegumental
      protein from Schistosoma japonicum.
AB  - Glutamine synthetase catalyzes the synthesis of glutamine, providing nitrogen for
      the production of purines, pyrimidines, amino acids, and other compounds required
      in many pivotal cellular events. Herein, a full-length cDNA encoding Schistosoma
      japonicum glutamine synthetase (SjGS) was isolated from 21-day schistosomes. The
      entire open reading frame of SjGS contains a 1,095-bp coding region corresponding
      to 364 amino acids with a calculated molecular weight of 40.7 kDa. NCBIP blast
      shows that the putative amino acid of SjGS contains a classic beta-grasp domain
      and a catalytic domain of glutamine synthetase. The relative mRNA expression of
      SjGS was evaluated in 7-, 13-, 21-, 28-, 35-, and 42-day worms of S. japonicum in
      the final host and higher expression at day 21, and 42 worms were observed. This
      protein was also detected in worm extracts using Western blot. Immunofluorescence
      studies indicated that the SjGS protein was mainly distributed on tegument and
      parenchyma in 28-day adult worms. The recombinant glutamine synthetase with a
      molecular weight of 45 kDa was expressed in Escherichia coli and purified in its
      active form. The enzyme activity of the recombinant protein was 3.30 +/- 0.67
      U.MUg-1. The enzyme activity was highly stable over a wide range of pH (6-9) and
      temperature (25-40  degrees C) under physiological conditions. The transcription
      of SjGS was upregulated in praziquantel-treated worms at 2-, 4-, and 24-h
      posttreatment compared with the untreated control. As a first step towards the
      clarification of the role of glutamine synthetase in schistosome species, we have
      cloned and characterized cDNAs encoding SjGS in S. japonicum, and the data
      presented suggest that SjGS is an important molecule in the development of the
      schistosome.

PMID- 23011790
TI  - Total synthesis of the nominal didemnaketal A.

PMID- 23011791
TI  - The diagnosis and management of congenital hemophilia.
AB  - Hemophilia is the most common, severe, inherited bleeding disorder recognized in
      humans and makes up the largest proportion of patients followed in most bleeding
      disorders' clinics. Persons with hemophilia have a life-long bleeding tendency
      that roughly correlates to their endogenous coagulant factor VIII (FVIII) or
      factor IX (FIX) level (FVIII:C and FIX:C). The hallmark of bleeding in severe
      hemophilia is musculoskeletal bleeds (soft tissue, muscle and joint bleeds) but
      persons with hemophilia are also prone to other bleeds including intracranial
      bleeds. The neonatal period is a particularly vulnerable period for persons with
      severe hemophilia. Diagnosing hemophilia is mainly based on measuring FVIII:C and
      FIX:C levels and on distinguishing hemophilia from other conditions that can
      cause a low FVIII:C or FIX:C level. Management involves preventing bleeds and
      rapidly treating those that occur. Bleed prevention in severe hemophilia can be
      accomplished by avoiding high-risk activities, taking appropriate precautions and
      early commencement of life-long prophylaxis. With proper management, persons with
      severe hemophilia can now live an essentially normal life. The development of an
      inhibitor does however complicate management. This review will summarize the very
      complex and multifaceted aspects of diagnosing and managing persons with
      hemophilia.

PMID- 23011792
TI  - Laboratory investigations for bleeding disorders.
AB  - Bleeding disorder panels often include the prothrombin time (PT)/international
      normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen
      level, and thrombin time (TT). We explored the detection of abnormalities from
      bleeding disorders by these tests among subjects referred for bleeding disorder
      assessments, using data from a bleeding disorder study to determine sensitivities
      and specificities. Among subjects referred to hematologists for bleeding disorder
      assessment, coagulation defects were uncommon and the APTT and TT detected many
      nonsignificant abnormalities. While all test and panel specificities were
      acceptable (88 to 100%), coagulation screening tests were less sensitive to
      clinically significant abnormalities (1.0 to 2.1%) than von Willebrand disease
      (VWD) screens (6.7%), and light transmission platelet aggregometry (LTA) (26%).
      Accordingly, panels comprising PT/INR, APTT, fibrinogen, and TT had lower
      sensitivity to bleeding disorders (3.7%) than panels expanded to include VWD
      screens (8.5%), or VWD screens and LTA (30%). These findings have important
      implications for bleeding disorder diagnosis.

PMID- 23011793
TI  - Pineapple stem bromelain immobilized on different supports: catalytic properties
      in model wine.
AB  - Bromelain from pineapple stem has been covalently immobilized on different
      supports to select the more efficient biocatalyst that should be applied toward
      unstable proteins in real white wine. In this preliminary study, catalytic
      properties of different immobilized bromelain forms were compared under wine-like
      conditions, against a synthetic substrate (Bz-Phe-Val-Arg-pNA).Covalent
      immobilization affected protease kinetic properties, even if all immobilized
      forms presented both a better substrate affinity and higher half-life (with the
      exception of a few procedures) with respect to the free enzyme. Stem bromelain
      was successfully immobilized on chitosan beads without glutaraldehyde thus
      yielding a food-safe and promising biocatalyst for unstable real wine future
      application.

PMID- 23011794
TI  - Small-molecule histone methyltransferase inhibitors display rapid antimalarial
      activity against all blood stage forms in Plasmodium falciparum.
AB  - Epigenetic factors such as histone methylation control the developmental
      progression of malaria parasites during the complex life cycle in the human host.
      We investigated Plasmodium falciparum histone lysine methyltransferases as a
      potential target class for the development of novel antimalarials. We synthesized
      a compound library based upon a known specific inhibitor (BIX-01294) of the human
      G9a histone methyltransferase. Two compounds, BIX-01294 and its derivative TM2
      115, inhibited P. falciparum 3D7 parasites in culture with IC(50) values of ~100
      nM, values at least 22-fold more potent than their apparent IC(50) toward two
      human cell lines and one mouse cell line. These compounds irreversibly arrested
      parasite growth at all stages of the intraerythrocytic life cycle. Decrease in
      parasite viability (>40%) was seen after a 3-h incubation with 1 uM BIX-01294 and
      resulted in complete parasite killing after a 12-h incubation. Additionally, mice
      with patent Plasmodium berghei ANKA strain infection treated with a single dose
      (40 mg/kg) of TM2-115 had 18-fold reduced parasitemia the following day.
      Importantly, treatment of P. falciparum parasites in culture with BIX-01294 or
      TM2-115 resulted in significant reductions in histone H3K4me3 levels in a
      concentration-dependent and exposure time-dependent manner. Together, these
      results suggest that BIX-01294 and TM2-115 inhibit malaria parasite histone
      methyltransferases, resulting in rapid and irreversible parasite death. Our data
      position histone lysine methyltransferases as a previously unrecognized target
      class, and BIX-01294 as a promising lead compound, in a presently unexploited
      avenue for antimalarial drug discovery targeting multiple life-cycle stages.

PMID- 23011795
TI  - TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4)
      regulates CD8+ T-cell differentiation.
AB  - CD8(+) T-cell development in the thymus generates a predominant population of
      conventional naive cells, along with minor populations of "innate" T cells that
      resemble memory cells. Recent studies analyzing a variety of KO or knock-in mice
      have indicated that impairments in the T-cell receptor (TCR) signaling pathway
      produce increased numbers of innate CD8(+) T cells, characterized by their high
      expression of CD44, CD122, CXCR3, and the transcription factor, Eomesodermin
      (Eomes). One component of this altered development is a non-CD8(+) T cell
      intrinsic role for IL-4. To determine whether reduced TCR signaling within the
      CD8(+) T cells might also contribute to this pathway, we investigated the role of
      the transcription factor, IFN regulatory factor 4 (IRF4). IRF4 is up-regulated
      following TCR stimulation in WT T cells; further, this up-regulation is impaired
      in T cells treated with a small-molecule inhibitor of the Tec family tyrosine
      kinase, IL-2 inducible T-cell kinase (ITK). In contrast to WT cells, activation
      of IRF4-deficient CD8(+) T cells leads to rapid and robust expression of Eomes,
      which is further enhanced by IL-4 stimulation. In addition, inhibition of ITK
      together with IL-4 increases Eomeso up-regulation. These data indicate that ITK
      signaling promotes IRF4 up-regulation following CD8(+) T-cell activation and that
      this signaling pathway normally suppresses Eomes expression, thereby regulating
      the differentiation pathway of CD8(+) T cells.

PMID- 23011796
TI  - Direct observation of proteolytic cleavage at the S2 site upon forced unfolding
      of the Notch negative regulatory region.
AB  - The conserved Notch signaling pathway plays crucial roles in developing and self
      renewing tissues. Notch is activated upon ligand-induced conformation change of
      the Notch negative regulatory region (NRR) unmasking a key proteolytic site (S2)
      and facilitating downstream events. Thus far, the molecular mechanism of this
      signal activation is not defined. However, strong indirect evidence favors a
      model whereby transendocytosis of the Notch extracellular domain, in tight
      association with ligand into the ligand-bearing cell, exerts a force on the NRR
      to drive the required structure change. Here, we demonstrate that force applied
      to the human Notch2 NRR can indeed expose the S2 site and, crucially, allow
      cleavage by the metalloprotease TACE (TNF-alpha-converting enzyme). Molecular
      insight into this process is achieved using atomic force microscopy and molecular
      dynamics simulations on the human Notch2 NRR. The data show near-sequential
      unfolding of its constituent LNR (Lin12-Notch repeat) and HD (heterodimerization)
      domains, at forces similar to those observed for other protein domains with a
      load-bearing role. Exposure of the S2 site is the first force "barrier" on the
      unfolding pathway, occurring prior to unfolding of any domain, and achieved via
      removal of the LNRAB linker region from the HD domain. Metal ions increase the
      resistance of the Notch2 NRR to forced unfolding, their removal clearly
      facilitating unfolding at lower forces. The results provide direct demonstration
      of force-mediated exposure and cleavage of the Notch S2 site and thus firmly
      establish the feasibility of a mechanotransduction mechanism for ligand-induced
      Notch activation.

PMID- 23011797
TI  - Canonical Wnt signaling regulates Slug activity and links epithelial-mesenchymal
      transition with epigenetic Breast Cancer 1, Early Onset (BRCA1) repression.
AB  - Slug (Snail2) plays critical roles in regulating the epithelial-mesenchymal
      transition (EMT) programs operative during development and disease. However, the
      means by which Slug activity is controlled remain unclear. Herein we identify an
      unrecognized canonical Wnt/GSK3beta/beta-Trcp1 axis that controls Slug activity.
      In the absence of Wnt signaling, Slug is phosphorylated by GSK3beta and
      subsequently undergoes beta-Trcp1-dependent ubiquitination and proteosomal
      degradation. Alternatively, in the presence of canonical Wnt ligands, GSK3beta
      kinase activity is inhibited, nuclear Slug levels increase, and EMT programs are
      initiated. Consistent with recent studies describing correlative associations in
      basal-like breast cancers between Wnt signaling, increased Slug levels, and
      reduced expression of the tumor suppressor Breast Cancer 1, Early Onset (BRCA1),
      further studies demonstrate that Slug-as well as Snail-directly represses BRCA1
      expression by recruiting the chromatin-demethylase, LSD1, and binding to a series
      of E-boxes located within the BRCA1 promoter. Consonant with these findings,
      nuclear Slug and Snail expression are increased in association with BRCA1
      repression in a cohort of triple-negative breast cancer patients. Together, these
      findings establish unique functional links between canonical Wnt signaling, Slug
      expression, EMT, and BRCA1 regulation.

PMID- 23011798
TI  - Selectively altering belief formation in the human brain.
AB  - Humans form beliefs asymmetrically; we tend to discount bad news but embrace good
      news. This reduced impact of unfavorable information on belief updating may have
      important societal implications, including the generation of financial market
      bubbles, ill preparedness in the face of natural disasters, and overly aggressive
      medical decisions. Here, we selectively improved people's tendency to incorporate
      bad news into their beliefs by disrupting the function of the left (but not
      right) inferior frontal gyrus using transcranial magnetic stimulation, thereby
      eliminating the engrained "good news/bad news effect." Our results provide an
      instance of how selective disruption of regional human brain function
      paradoxically enhances the ability to incorporate unfavorable information into
      beliefs of vulnerability.

PMID- 23011799
TI  - ORMDL3 is an inducible lung epithelial gene regulating metalloproteases,
      chemokines, OAS, and ATF6.
AB  - Orosomucoid like 3 (ORMDL3) has been strongly linked with asthma in genetic
      association studies, but its function in asthma is unknown. We demonstrate that
      in mice ORMDL3 is an allergen and cytokine (IL-4 or IL-13) inducible endoplasmic
      reticulum (ER) gene expressed predominantly in airway epithelial cells. Allergen
      challenge induces a 127-fold increase in ORMDL3 mRNA in bronchial epithelium in
      WT mice, with lesser 15-fold increases in ORMDL-2 and no changes in ORMDL-1.
      Studies of STAT-6-deficient mice demonstrated that ORMDL3 mRNA induction highly
      depends on STAT-6. Transfection of ORMDL3 in human bronchial epithelial cells in
      vitro induced expression of metalloproteases (MMP-9, ADAM-8), CC chemokines (CCL
      20), CXC chemokines (IL-8, CXCL-10, CXCL-11), oligoadenylate synthetases (OAS)
      genes, and selectively activated activating transcription factor 6 (ATF6), an
      unfolded protein response (UPR) pathway transcription factor. siRNA knockdown of
      ATF-6alpha in lung epithelial cells inhibited expression of SERCA2b, which has
      been implicated in airway remodeling in asthma. In addition, transfection of
      ORMDL3 in lung epithelial cells activated ATF6alpha and induced SERCA2b. These
      studies provide evidence of the inducible nature of ORMDL3 ER expression in
      particular in bronchial epithelial cells and suggest an ER UPR pathway through
      which ORMDL3 may be linked to asthma.

PMID- 23011800
TI  - Remote control of DNA-acting enzymes by varying the Brownian dynamics of a
      distant DNA end.
AB  - Enzyme rates are usually considered to be dependent on local properties of the
      molecules involved in reactions. However, for large molecules, distant
      constraints might affect reaction rates by affecting dynamics leading to
      transition states. In single-molecule experiments we have found that enzymes that
      relax DNA torsional stress display rates that depend strongly on how the distant
      ends of the molecule are constrained; experiments with different-sized particles
      tethered to the end of 10-kb DNAs reveal enzyme rates inversely correlated with
      particle drag coefficients. This effect can be understood in terms of the
      coupling between molecule extension and local molecular stresses: The rate of
      bead thermal motion controls the rate at which transition states are visited in
      the middle of a long DNA. Importantly, we have also observed this effect for
      reactions on unsupercoiled DNA; other enzymes show rates unaffected by bead size.
      Our results reveal a unique mechanism through which enzyme rates can be
      controlled by constraints on macromolecular or supramolecular substrates.

PMID- 23011801
TI  - Enantioselective rhodium-catalyzed synthesis of branched allylic amines by
      intermolecular hydroamination of terminal allenes.

PMID- 23011802
TI  - Combined butalbital/acetaminophen/caffeine overdose: case files of the Robert
      Wood Johnson Medical School Toxicology Service.

PMID- 23011803
TI  - Solution structures of polcalcin Phl p 7 in three ligation states: Apo-, hemi
      Mg2+-bound, and fully Ca2+-bound.
AB  - Polcalcins are small EF-hand proteins believed to assist in regulating pollen
      tube growth. Phl p 7, from timothy grass (Phleum pratense), crystallizes as a
      domain-swapped dimer at low pH. This study describes the solution structures of
      the recombinant protein in buffered saline at pH 6.0, containing either 5.0 mM
      EDTA, 5.0 mM Mg(2+), or 100 MUM Ca(2+). Phl p 7 is monomeric in all three
      ligation states. In the apo-form, both EF-hand motifs reside in the closed
      conformation, with roughly antiparallel N- and C-terminal helical segments. In
      5.0 mM Mg(2+), the divalent ion is bound by EF-hand 2, perturbing interhelical
      angles and imposing more regular helical structure. The structure of Ca(2+)-bound
      Phl p 7 resembles that previously reported for Bet v 4-likewise exposing apolar
      surface to the solvent. Occluded in the apo- and Mg(2+)-bound forms, this surface
      presumably provides the docking site for Phl p 7 targets. Unlike Bet v 4, EF-hand
      2 in Phl p 7 includes five potential anionic ligands, due to replacement of the
      consensus serine residue at -x (residue 55 in Phl p 7) with aspartate. In the Phl
      p 7 crystal structure, D55 functions as a helix cap for helix D. In solution,
      however, D55 apparently serves as a ligand to the bound Ca(2+). When Mg(2+)
      resides in site 2, the D55 carboxylate withdraws to a distance consistent with a
      role as an outer-sphere ligand. (15)N relaxation data, collected at 600 MHz,
      indicate that backbone mobility is limited in all three ligation states.

PMID- 23011804
TI  - Evolving role of GTP cyclohydrolase 1 inhibition in mitigating cancer pain
      besides its role in attenuating tumor growth.

PMID- 23011805
TI  - Automatic intra-subject registration-based segmentation of abdominal fat from
      water-fat MRI.
AB  - PURPOSE: To develop an automatic registration-based segmentation algorithm for
      measuring abdominal adipose tissue depot volumes and organ fat fraction content
      from three-dimensional (3D) water-fat MRI data, and to evaluate its performance
      against manual segmentation. MATERIALS AND METHODS: Data were obtained from 11
      subjects at two time points with intermediate repositioning, and from four
      subjects before and after a meal with repositioning. Imaging was performed on a 3
      Tesla MRI, using the IDEAL chemical-shift water-fat pulse sequence. Adipose
      tissue (subcutaneous--SAT, visceral--VAT) and organs (liver, pancreas) were
      manually segmented twice for each scan by a single trained observer. Automated
      segmentations of each subject's second scan were generated using a nonrigid
      volume registration algorithm for water-fat MRI images that used a b-spline basis
      for deformation and minimized image dissimilarity after the deformation. Manual
      and automated segmentations were compared using Dice coefficients and linear
      regression of SAT and VAT volumes, organ volumes, and hepatic and pancreatic fat
      fractions (HFF, PFF). RESULTS: Manual segmentations from the 11 repositioned
      subjects exhibited strong repeatability and set performance benchmarks. The
      average Dice coefficients were 0.9747 (SAT), 0.9424 (VAT), 0.9404 (liver), and
      0.8205 (pancreas); the linear correlation coefficients were 0.9994 (SAT volume),
      0.9974 (VAT volume), 0.9885 (liver volume), 0.9782 (pancreas volume), 0.9996
      (HFF), and 0.9660 (PFF). When comparing manual and automated segmentations, the
      average Dice coefficients were 0.9043 (SAT volume), 0.8235 (VAT), 0.8942 (liver),
      and 0.7168 (pancreas); the linear correlation coefficients were 0.9493 (SAT
      volume), 0.9982 (VAT volume), 0.9326 (liver volume), 0.8876 (pancreas volume),
      0.9972 (HFF), and 0.8617 (PFF). In the four pre- and post-prandial subjects, the
      Dice coefficients were 0.9024 (SAT), 0.7781 (VAT), 0.8799 (liver), and 0.5179
      (pancreas); the linear correlation coefficients were 0.9889, 0.9902 (SAT, and VAT
      volume), 0.9523 (liver volume), 0.8760 (pancreas volume), 0.9991 (HFF), and
      0.6338 (PFF). CONCLUSION: Automated intra-subject registration-based segmentation
      is potentially suitable for the quantification of abdominal and organ fat and
      achieves comparable quantitative endpoints with respect to manual segmentation.

PMID- 23011807
TI  - Treatment of dyssomnias and parasomnias in childhood.
AB  - OPINION STATEMENT: Dyssomnias are sleep disorders associated with complaints of
      insomnia or hypersomnia. The daytime sleepiness of narcolepsy is treated by a
      combination of planned daytime naps, regular exercise medications such as
      modafinil, or salts of methylphenidate, or amphetamine. Cataplexy that
      accompanies narcolepsy is treated with anticholinergic agents, selective
      serotonin reuptake inhibitors, or sodium oxybate. Children with
      neurodevelopmental disabilities such as autism have sleep initiation and
      maintenance difficulties on a multifactorial basis, with favorable response to
      melatonin in some patients. Childhood onset restless legs syndrome is often
      familial, associated with systemic iron deficiency, and responsive to iron
      supplementation and gabapentin. Parasomnias are episodic phenomena events which
      occur at the sleep -- wake transition or by intrusion on to sleep. Arousal
      parasomnias such as confusional arousals and sleep walking can sometimes be
      confused with seizures. A scheme for differentiating arousal parasomnias from
      nocturnal seizures is provided. Since arousal parasomnias are often triggered by
      sleep apnea, restless legs syndrome, or acid reflux, treatment measures directed
      specifically at these disorders often helps in resolution. Clonazepam provided in
      a low dose at bedtime can also alleviate sleep walking and confusional arousals.
      Obstructive sleep apnea affects about 2 percent of children. Adeno-tonsillar
      hypertrophy, cranio-facial anomalies, and obesity are common predisposing
      factors. Mild obstructive sleep apnea can be treated using a combination of nasal
      corticosteroids and a leukotriene antagonist. Moderate to severe obstructive
      sleep apnea are treated with adeno-tonsillectomy, positive airway pressure
      breathing devices, or weight reduction as indicated. This paper provides an
      overview of the topic, with an emphasis on management steps. Where possible, the
      level of evidence for treatment recommendations is indicated.

PMID- 23011806
TI  - The crystal structure of the Rv0301-Rv0300 VapBC-3 toxin-antitoxin complex from
      M. tuberculosis reveals a Mg2+ ion in the active site and a putative RNA-binding
      site.
AB  - VapBC pairs account for 45 out of 88 identified toxin-antitoxin (TA) pairs in the
      Mycobacterium tuberculosis (Mtb) H37Rv genome. A working model suggests that
      under times of stress, antitoxin molecules are degraded, releasing the toxins to
      slow the metabolism of the cell, which in the case of VapC toxins is via their
      RNase activity. Otherwise the TA pairs remain bound to their promoters,
      autoinhibiting transcription. The crystal structure of Rv0301-Rv0300, an Mtb
      VapBC TA complex determined at 1.49 A resolution, suggests a mechanism for these
      three functions: RNase activity, its inhibition by antitoxin, and its ability to
      bind promoter DNA. The Rv0301 toxin consists of a core of five parallel beta
      strands flanked by alpha helices. Three proximal aspartates coordinate a Mg2+ ion
      forming the putative RNase active site. The Rv0300 antitoxin monomer is extended
      in structure, consisting of an N-terminal beta strand followed by four helices.
      The last two helices wrap around the toxin and terminate near the putative RNase
      active site, but with different conformations. In one conformation, the C
      terminal arginine interferes with Mg2+ ion coordination, suggesting a mechanism
      by which the antitoxin can inhibit toxin activity. At the N-terminus of the
      antitoxin, two pairs of Ribbon-Helix-Helix (RHH) motifs are related by
      crystallographic twofold symmetry. The resulting hetero-octameric complex is
      similar to the FitAB system, but the two RHH motifs are about 30 A closer
      together in the Rv0301-Rv0300 complex, suggesting either a different span of the
      DNA recognition sequence or a conformational change.

PMID- 23011808
TI  - A major X-linked locus affects kidney function in mice.
AB  - Chronic kidney disease is a common disease with increasing prevalence in the
      western population. One common reason for chronic kidney failure is diabetic
      nephropathy. Diabetic nephropathy and hyperglycemia are characteristics of the
      mouse inbred strain KK/HlJ, which is predominantly used as a model for metabolic
      syndrome due to its inherited glucose intolerance and insulin resistance. We used
      KK/HlJ, an albuminuria-sensitive strain, and C57BL/6J, an albuminuria-resistant
      strain, to perform a quantitative trait locus (QTL) cross to identify the genetic
      basis for chronic kidney failure. Albumin-creatinine ratio (ACR) was measured in
      130 F2 male offspring. One significant QTL was identified on chromosome (Chr) X
      and four suggestive QTL were found on Chrs 6, 7, 12, and 13. Narrowing of the QTL
      region was focused on the X-linked QTL and performed by incorporating genotype
      and expression analyses for genes located in the region. From the 485 genes
      identified in the X-linked QTL region, a few candidate genes were identified
      using a combination of bioinformatic evidence based on genomic comparison of the
      parental strains and known function in urine homeostasis. Finally, this study
      demonstrates the significance of the X chromosome in the genetic determination of
      albuminuria.

PMID- 23011811
TI  - Assisted-living spaces for end-users with complex needs: a proposed
      implementation and delivery model.
AB  - An assisted living space (ALS) is a technology-enabled environment designed to
      allow people with complex health or social care needs to remain, and live
      independently, in their own home for longer. However, many challenges remain in
      order to deliver usable systems acceptable to a diverse range of stakeholders,
      including end-users, and their families and carers, as well as health and social
      care services. ALSs need to support activities of daily-living while allowing end
      users to maintain important social connections. They must be dynamic, flexible
      and adaptable living environments. In this article, we provide an overview of the
      technological landscape of assisted-living technology (ALT) and recent policies
      to promote an increased adoption of ALT in Scotland. We discuss our experiences
      in implementing technology-supported ALSs and emphasise key lessons. Finally, we
      propose an iterative and pragmatic user-centred implementation model for
      delivering ALSs in complex-needs scenarios. This empirical model is derived from
      our past ALS implementations. The proposed model allows project stakeholders to
      identify requirements, allocate tasks and responsibilities, and identify
      appropriate technological solutions for the delivery of functional ALS systems.
      The model is generic and makes no assumptions on needs or technology solutions,
      nor on the technical knowledge, skills and experience of the stakeholders
      involved in the ALS design process.

PMID- 23011809
TI  - Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the
      mitochondrial membrane potential in reactive oxygen species generation.
AB  - Stroke and circulatory arrest cause interferences in blood flow to the brain that
      result in considerable tissue damage. The primary method to reduce or prevent
      neurologic damage to patients suffering from brain ischemia is prompt restoration
      of blood flow to the ischemic tissue. However, paradoxically, restoration of
      blood flow causes additional damage and exacerbates neurocognitive deficits among
      patients who suffer a brain ischemic event. Mitochondria play a critical role in
      reperfusion injury by producing excessive reactive oxygen species (ROS) thereby
      damaging cellular components, and initiating cell death. In this review, we
      summarize our current understanding of the mechanisms of mitochondrial ROS
      generation during reperfusion, and specifically, the role the mitochondrial
      membrane potential plays in the pathology of cerebral ischemia/reperfusion.
      Additionally, we propose a temporal model of ROS generation in which
      posttranslational modifications of key oxidative phosphorylation (OxPhos)
      proteins caused by ischemia induce a hyperactive state upon reintroduction of
      oxygen. Hyperactive OxPhos generates high mitochondrial membrane potentials, a
      condition known to generate excessive ROS. Such a state would lead to a "burst"
      of ROS upon reperfusion, thereby causing structural and functional damage to the
      mitochondria and inducing cell death signaling that eventually culminate in
      tissue damage. Finally, we propose that strategies aimed at modulating this
      maladaptive hyperpolarization of the mitochondrial membrane potential may be a
      novel therapeutic intervention and present specific studies demonstrating the
      cytoprotective effect of this treatment modality.

PMID- 23011812
TI  - Developing visualisation software for rehabilitation: investigating the
      requirements of patients, therapists and the rehabilitation process.
AB  - This article describes the ongoing process of engaging with users in the
      development and evaluation of prototype visualisation software, which aims to
      assist in the understanding and improvement of appropriate movements during
      rehabilitation. The value of the process is illustrated in the article with a
      discussion of the key findings of pre-pilot focus groups with stroke survivors
      and therapists. The article describes how the design of the visualisation
      software is being adapted to meet the emerging understanding of the needs of
      patients and professionals, and of the rehabilitation process.

PMID- 23011813
TI  - Older users, multimodal reminders and assisted living technology.
AB  - The primary users of assisted living technology are older people who are likely
      to have one or more sensory impairments. Multimodal technology allows users to
      interact via non-impaired senses and provides alternative ways to interact if
      primary interaction methods fail. An empirical user study was carried out with
      older participants which evaluated the performance, disruptiveness and subjective
      workload of visual, audio, tactile and olfactory notifications then compared the
      results with earlier findings in younger participants. It was found that
      disruption and subjective workload were not affected by modality, although some
      modalities were more effective at delivering information accurately. It is
      concluded that although further studies need to be carried out in a real-world
      settings, the findings support the argument for multiple modalities in assisted
      living technology.

PMID- 23011814
TI  - Privacy and data security in E-health: requirements from the user's perspective.
AB  - In this study two currently relevant aspects of using medical assistive
      technologies were addressed-security and privacy. In a two-step empirical
      approach that used focus groups (n = 19) and a survey (n = 104), users'
      requirements for the use of medical technologies were collected and evaluated.
      Specifically, we focused on the perceived importance of data security and privacy
      issues. Outcomes showed that both security and privacy aspects play an important
      role in the successful adoption of medical assistive technologies in the home
      environment. In particular, analysis of data with respect to gender, health
      status and age (young, middle-aged and old users) revealed that females and
      healthy adults require, and insist on, the highest security and privacy standards
      compared with males and the ailing elderly.

PMID- 23011815
TI  - Looking for similarities in movement between and within homes using cluster
      analysis.
AB  - In this article we examine data from eight purpose-built aware homes over a six
      month period, looking at presence in rooms to try to determine patterns among the
      older residents. We look for homes that have similar movement patterns using
      cluster analysis. We also examine how movement over days clusters within
      individual homes. Our analysis shows that different homes have distinct movement
      patterns but within individual homes residents have strong movement routines.

PMID- 23011816
TI  - A blended design approach for pervasive healthcare: bringing together users,
      experts and technology.
AB  - Pervasive healthcare is beginning to investigate how novel sensory technologies
      can be used to measure body movements and provide various forms of feedback. This
      position paper reflects on a blended design approach that uses a combination of
      technology inspiration, consultation with experts and user-centred design for the
      development of a personalized pervasive healthcare system to support stroke
      rehabilitation.

PMID- 23011817
TI  - How will we know if it's working? A multi-faceted approach to measuring usability
      of a specialty-specific electronic medical record.
AB  - The most effective use of electronic medical records (EMRs) will result from wide
      scale adoption and appropriate use of the technology-two factors that rely
      heavily on a system's usability. We conducted a qualitative and quantitative
      usability assessment of an EMR developed specifically for treating the HIV/AIDS
      patient population. The purpose of this study was to inform developers on how to
      prioritize resources for their impending software rebuild initiative and to
      evaluate a dual methodology consisting of both quantitative and qualitative
      components. The results indicated that the methodology was valid, although there
      were some variations recommended for future usability assessments of EMRs. The
      study also underscored the need to assess usability based on user feedback and to
      employ multiple methods to elicit information; this research revealed many
      insights into the software that contradicted initial assumptions and also found
      that asking questions in multiple ways yielded more complete feedback.

PMID- 23011810
TI  - Overlapped metabolic and therapeutic links between Alzheimer and diabetes.
AB  - Alzheimer's disease (AD) and diabetes are among the most common diseases
      associated with ageing. The pathology of AD is strongly associated with
      accumulated misfolding proteins that results in neuronal dysfunction within the
      brain. Diabetes, on the contrary, is characterised by altered insulin signaling
      that results in reduced glucose uptake, metabolic suppression of energy consuming
      cells and conversion of glucose to fat in the liver. Despite distinguishing
      features, these diseases share common elements and may in fact be viewed as
      fundamentally similar disorders that differ in magnitude of specific traits,
      primarily affected tissues and time of onset. In this review, we outline the
      fundamental basis of each of the two diseases and highlight similarities in their
      pathophysiology. Further ahead we will discuss these features in relation to the
      development of drugs to treat these two diseases, particularly AD, for which the
      development of therapeutic chemicals has proven to be particularly difficult. We
      conclude with comments on efforts to develop a simple organism, Caenorhabditis
      elegans, as a genetic model to be used to study the systems biology of diabetes
      and AD.

PMID- 23011818
TI  - Blooms of the millennium.
AB  - This article narrates the efforts being made to bring a new spring into the lives
      of Arab women with breast cancer in the progressive nation of the Sultanate of
      Oman. It is an inspiration and role model for other nations that treasure the
      cause of promoting women's health in the fight against cancer.

PMID- 23011819
TI  - Programmable magnetic tweezers and droplet microfluidic device for high
      throughput nanoliter multi-step assays.

PMID- 23011820
TI  - Who owns these tissues? General principles on the use of material submitted to
      pathology departments for healthcare, education and research purposes.
AB  - The study of human tissues procured through invasive procedures for diagnostic   
      and treatment purposes constitutes one of the most important functions of    
      pathology departments worldwide. The final diagnosis, determination of    
      appropriate therapy and detailed insight on many diseases are possible only    
      through the analysis of these tissues with the use of modern analytical    
      techniques. While these statements present no controversy, the laws and    
      regulations on how to use these tissues for diagnostic, educational and research 
      purposes are woefully insufficient and cause significant debate. In addition
      to     the lack of principles that define the possession and use of these
      tissues,     there are a number of prejudices in our country that are not
      consistent with the     scientific and medical facts. This study aims to frame
      the problems arising in     this matter and provides a review of the rules,
      experience and legislation in     various countries with a discussion of some
      examples. We aim to provide ideas on     the general fundamental principles that
      should be incorporated in future     legislation in our country. We also hope
      that our study initiates a healthy     discussion of this critical topic.

PMID- 23011821
TI  - The situation of consultation practice in pathology in Turkey.
AB  - OBJECTIVE: There are some suggestions regarding the methods of consultation
      practice in the literature including which case will be consulted, to whom, by
      which transport means, the payment methods as well as the ethical issues. There
      are no standards for consultations in Turkey. The standardization committee of
      the Federation of Turkish Pathology Societies has conducted a survey to detect
      the current situation, determine the problematic aspects, compare the situation
      with international methods and offer methods specific to Turkey. MATERIAL AND
      METHOD: A survey has been prepared to cover all the aspects of consultation
      practice using the literature and referring to the current methods used in
      Turkey. The survey has been announced on the internet and 83 replies were
      collected. RESULTS: Multiple choice questions were evaluated in terms of
      percentages and open ended questions were grouped according to the answer
      contents. It was seen that problems could be grouped as follows: absence of
      written procedures covering each step, means of transport, reaching the
      consultant, payment, reporting and ethical issues. The absence of procedures and
      issues regarding the payment methods were the interfering factors for each step
      of consultation. CONCLUSION: There are many problematic issues in consultation
      practice in pathology in Turkey. The basis of these problems is the absence of
      written regulations for procedural and payment methods. Regulations addressing
      these issues should be developed.

PMID- 23011822
TI  - Digitally reinforced polarization of hematoxylin-eosin in the diagnosis of renal
      amyloidosis.
AB  - OBJECTIVE: Systemic amyloidosis is a rare disorder, characterized by
      extracellular accumulation of Congo red positive fibrillar amyloid protein
      deposits that have an amorphous, eosinophilic appearance on hematoxylin-eosin
      stained preparations. The kidney is the most commonly affected organ by systemic
      amyloidosis. Congo red staining increases the positive birefringence of the
      weakly birefringent unstained amyloid. In this study, we investigated the
      potential diagnostic power of digitally reinforced birefringence of routine
      hematoxylin-eosin stained slides from renal biopsies. MATERIAL AND METHOD: We
      reviewed 130 hematoxylin-eosin stained slides for polarization. Sixty-five new
      amyloidosis cases were diagnosed by renal biopsy. All renal biopsies were
      evaluated by light microscopy and immunofluorescence. Slides were reevaluated
      blindly using a microscope (Olympus BX51) that was attached polarization filters
      and connected to a digital camera (Olympus DP21, SAL). Deposits that showed green
      birefringence on hematoxylin-eosin preparations with digitalized microscopy were
      considered positive and the results were confirmed using Congo red. RESULTS: Of
      the 65 Congo red confirmed amyloid positive biopsies, 61 showed green
      birefringence with hematoxylin-eosin. Of the 65 Congo-red confirmed amyloid
      negative biopsies, two were considered to be false positive. The sensitivity,
      specificity, and positive and negative predictive values were estimated as 94%,
      97%, 97% and 94% respectively. CONCLUSION: We concluded that polarized
      hematoxylin-eosin sections can be used digitally as a fast and first step
      diagnostic method for renal amyloidosis.

PMID- 23011823
TI  - The selective expression of ret finger protein in endometrial cancer: can RFP be
      a marker of serous carcinomas?
AB  - OBJECTIVE: Endometrial cancer is a common malignancy of the gynecological system
      and has been classified into two major groups, Types I and II. Type I tumors are
      estrogen-related, low-grade endometrioid tumors, whereas type II tumors are
      aggressive, high-grade non-endometrioid tumors. Ret finger protein is a nuclear
      transcription factor with a tripartite motif that is highly expressed in
      different tumor cells. MATERIAL AND METHOD: To analyze the expression of ret
      finger protein in endometrial tissues and cancer, 18 cases of secretory and
      proliferative endometrium, endometrial polyp, endometrial hyperplasia and
      endometrial intraepithelial neoplasia and 21 cases of types I and II endometrial
      carcinoma were evaluated immunohistochemically. RESULTS: Although rare cases of
      secretory endometrium showed a weak focal nuclear positivity, remaining
      proliferative endometrium, endometrial hyperplasia and type I endometrioid cancer
      cases were negative. In contrast, all cases of serous cancers showed strong
      nuclear positivity. After these strong positive results for serous endometrial
      cancer, 12 more cases of ovarian and endometrial serous carcinoma cases were
      added to the study. All of the additional cases were also strongly positive for
      ret finger protein. CONCLUSION: We suggest that ret finger protein might play a
      role in the carcinogenesis of the serous tumors of gynecological system and can
      be used to differentiate serous carcinomas from other epithelial tumors.

PMID- 23011824
TI  - Expression of p16, p53, CD24, EpCAM and calretinin in serous borderline tumors of
      the ovary.
AB  - OBJECTIVE: According to the widely accepted pathway, a serous borderline tumor
      becomes invasive either by progressing into a noninvasive micropapillary tumor or
      directly through microinvasion. Our objective was to investigate the role of
      serous borderline tumors and their accompanying extraovarian lesions in
      pathogenesis of serous ovarian cancer using immunohistochemistry as a tool.
      MATERIAL AND METHOD: An immunohistochemical panel of p16, p53, CD24, EpCAM and
      calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46
      cases consisting of typical, focal micropapillary, micropapillary, microinvasive,
      cystadenoma, and low-grade carcinoma cases. These tissue arrays are better
      choices than conventional tissue arrays to examine thin walled and heterogenous
      neoplasia like serous borderline tumors as they facilitate the analysis with
      linear sections rather than a core. RESULTS: For two tumor supressor gene
      markers; no diffuse and strong expression of p53, and strong and
      patchy/heterogenous expression of p16 were detected in all cases. Focal and
      strong calretinin expression was detected in micropapillary tumors while
      expression of EpCAM was lost in the same areas. Strong cytoplasmic CD24
      expression was detected in cases with peritoneal implants, favoring the theory
      that change of expression localization of cell adhesion molecules is in
      accordance with phenotypical changes and tumor progresssion. Furthermore,
      circumfrential membranous and cytoplasmic expression of CD24 and EpCAM was
      detected in neoplastic cells in lymph nodes and microinvasion areas. CONCLUSION:
      Our results show that different levels of serous ovarian tumor progression are
      accompanied by changes in the immunohistochemical expression pattern of EpCAM,
      CD24, and calretinin.

PMID- 23011825
TI  - [The influence of cervicovaginitis agents on epithelial cell changes: comparison
      of Mardin city's data with the literature].
AB  - OBJECTIVE: The aim of this paper was to observe the reactive changes of
      epithelial cells exposed to the influence of cervicovaginitis agents that play an
      important role in the cytology practice and may cause an exaggerated appearance.
      MATERIAL AND METHOD: 378 cases with cervicovaginitis caused by a specific agent
      were compared with 100 control cases. It was recorded if the inflammation had
      concomitant cellular changes and atypia or not. After treatment, control smears
      were examined. The reactive and atypical situations of the cells were considered
      after the treatment. With the aid of the previous data, the answer to the
      following question was searched: Is epithelial atypia a real event or a reactive
      atypia that accompanies an existing cervicitis agent? RESULTS: In the first
      interpretation, Candida group had the most frequent reactive and ASC-US (Atypic
      Squamous cells of Undetermined Significance) changes (56,4% and 59,5%
      respectively). The bacterial vaginosis and Trichomonas vaginalis groups showed
      ASC-US rates of 25% and 9,5% respectively while in control group the rate was
      6,0%. After treatment, the number of cases of ASC-US decreased from 50 to 11.
      Similarly, the number decreased from 21 to 10 in the bacterial vaginosis group.
      CONCLUSION: Cervicovaginitis agents need more attention because of their
      outcomes. Being aware of the cervicovaginitis agents during interpretation is
      essential for preventing a false positive diagnosis and unnecessary anxiety
      especially where cellular atypia is concerned.

PMID- 23011826
TI  - [Immunohistochemical characteristics of triple negative/basal-like breast
      cancer].
AB  - OBJECTIVE: Triple-negative-breast-cancer that accounts for 10-20% of all breast
      carcinomas is defined by the lack of estrogen receptor, progesterone receptor,
      HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer
      is categorized into basal like and other types. The basal-like subtype is
      characterized by the expression of myoepithelial/basal markers. MATERIAL AND
      METHOD: We studied 41 immunohistochemically triplenegative- breast-cancer
      patients to determine EGFR, Cytokeratine 5/6, p53, Ki67, GCDFP-15 expression
      profiles, HER2 and Chromosome 17 centromere gene status by fluorescence-in-situ
      hybridization method. RESULTS: Histological type was invasive ductal carcinoma in
      90.2% of the tumors. p53, Ki67, GCDFP-15 mean positivity rates were 55.6%, 51.7%,
      and 3.2%, respectively. GCDFP-15 positivity was noted in 8 cases of which 6 were
      Cytokeratine 5/6 negative. The cut-off value for Cytokeratine 5/6 positivity was
      5%. EGFR immunoreactivity was grouped into 0, 1+ as negative; 2+, 3+ as positive
      categories. Cytokeratine 5/6 was positive in 56,1%, EGFR was positive in 51.2% of
      the patients. The relation between Cytokeratine 5/6 and EGFR expression was
      statistically significant (p < 0.01). None of the cases showed HER2 amplification
      by fluorescence-in-situ-hybridization method. CONCLUSION: GCDFP-15 alone is not a
      useful marker to detect the metastasis of basaloid type breast cancers.
      Cytokeratine 5/6 and EGFR expressions showed correlation so these markers are
      reliable to diagnose basaloid type tumors with a 5% cut-off value.

PMID- 23011827
TI  - [The important morphological parameters used to differentiate benign/malignant
      phyllodes tumors of the breast].
AB  - OBJECTIVE: Phyllodes tumor is a rare fibroepithelial neoplasia of the breast.
      Tumors are classified according to the histological criteria as benign,
      borderline, malignant groups. Criteria used to discriminate benign/malignant
      cases are stromal cytological atypia, stromal hypercellularity, mitotic rate,
      stromal overgrowth, and tumor margins. We designed this study retrospectively to
      see the validity of these criteria for our case group and investigate whether we
      could add any new criteria. MATERIAL AND METHOD: We included 22 cases diagnosed
      as phyllodes tumor from our archives. Pathology records were used for age, tumor
      site, macroscopic size. The Hematoxylin-Eosin stained slides were reviewed
      according to the defined criteria. Additionally leaf like growth pattern, stromal
      hyalinization, calcification, stromal giant cells, stromal neutrophil leukocyte,
      and mononuclear lymphocytic infiltrate were recorded qualitatively
      (present/absent) and numerically (mild, moderate, severe). We examined the
      differences between benign and malignant groups with the Mann-Whitney U and chi
      square tests. RESULTS: The previously defined criteria were statistically
      significant but stromal giant cells, stromal hyalinization, calcification,
      stromal neutrophil and mononuclear lymphocytic infiltrate intensity were not
      statistically significant in determining the benign-borderline-malignant cases.
      CONCLUSION: Stromal hypercellularity, moderate/severe stromal cytological atypia,
      increased mitotic rate, stromal overgrowth and infiltrative tumor margins were
      observed in malignant phyllodes tumors. Malignant cases were also older and tumor
      size was bigger than benign ones.

PMID- 23011828
TI  - CDX2, COX2 and MUC2 expressions in Barrett's esophagus: can they be useful in
      determination of the dysplasia?
AB  - OBJECTIVE: The description of Barrett's esophagus which is a risk factor for
      esophageal adenocarcinoma has differences, and the need of goblet cells for
      diagnosis is controversial. However, the pathophysiology in the metaplasia seen
      in Barrett's esophagus is not totally understood and new methods are searched for
      the assessment of progression to dysplasia. We aimed to search the
      immunohistochemical expression of CDX2, COX2 and MUC2 in Barrett's esophagus to
      detect any early evidence of intestinal metaplasia or dysplasia. MATERIAL AND
      METHOD: The staining properties were examined in the intestinal metaplastic
      (goblet cell-containing columnar epithelium), columnar (non-goblet columnar
      epithelium), distant columnar (non-goblet columnar epithelium distant from
      intestinal metaplastic epithelium) and squamous epithelium in 59 pathologically
      diagnosed Barrett's esophagus, 22 of which having dysplasia. The results were
      compared statistically with Pearson and Fisher exact tests. RESULTS: The
      distribution of the staining of intestinal metaplastic, non-goblet columnar
      distant columnar, and squamous epithelium, respectively were as follows: for CDX2
      76.3%, 23.7%, 1.7%, 0%; for COX-2 93.2%, 47.5%, 8%, 62.9%; for MUC2 93.2%, 11.9%,
      4% and 0%. The expression of CDX2, COX2 and MUC2 in the intestinal metaplastic
      epithelium was higher than the expression in distant and non-goblet columnar
      epithelium. The expression of CDX2, COX2 and MUC2 in the foci of dysplasia
      decreased significantly (18.2%, 27.3%, 31.9%, and p=0.039, 0.0001, 0.0001,
      respectively). COX2 expression in squamous epithelium was also lower when the
      adjacent mucosa has dysplasia (p=0.014). CONCLUSION: The CDX2, COX2 and MUC2
      expressions were seen in the intestinal epithelium having goblet cells. The use
      of the markers in the diagnosis is controversial but the difference in the
      Barrett esophagus-dysplasia sequence seems to be meaningful.

PMID- 23011829
TI  - A regional panorama of dysferlinopathies.
AB  - OBJECTIVE: We describe the characteristic features of 11 patients (6 men and 5
      women) with dysferlinopathies confirmed by muscle biopsies. In addition, we aimed
      to provide a realistic comprehensive picture of the severe muscle diseases in the
      Aegean Region of Turkey. MATERIAL AND METHOD: We retrospectively reviewed 90
      patients who underwent muscle biopsy examinations between 2008 and 2011 in the
      pathology laboratory of Izmir Dr.Behcet Uz Children's Hospital. Biopsy specimens
      of all patients clinically diagnosed as muscular dystrophy referred from 4
      different centers of neurological disorders were collected. RESULTS:
      Dystrophinopathy was the most (n=45) and gammasarcoglycanopathy was the second
      common (n=13) muscular dystrophy in this series. The mean age of all 90 patients
      was 8.8 years (3 months- 64 years). Only 14 cases (15.5%) were older than 14, and
      23 cases were younger than two years. Dysferlinopathy was the most common
      dystrophy in the older age group. There were statistical significant differences
      between the types of dystrophy and inflammation (0.021), creatine kinase levels
      (p= 0.001), age (p=0.001), and gender (p < 0.001) of the patients. CONCLUSION:
      The present study revealed that dysferlinopathies is not an uncommon form of
      muscular dystrophies in western Turkey. We have concluded that if avoidance from
      unnecessary therapeutic interventions is desired, we must be aware of the
      relative frequencies of dysferlinopathies.

PMID- 23011830
TI  - Synovial sarcoma involving the median nerve: a case report.
AB  - Synovial sarcoma may arise from different and unusual sites. Here a case of    
      biphasic synovial sarcoma arising or invading the radial nerve in a 59-year-old  
      female classically showing chromosomal reciprocal translocation (X; 18) is    
      reported. The differential diagnosis from similar tumors is discussed.

PMID- 23011831
TI  - [A case of CD20 positive mediastinal rhabdomyosarcoma].
AB  - We present the case of a 16-year-old boy admitted with a large mediastinal mass. 
      Both in the mediastinal tru-cut biopsy and the bone marrow biopsy, a malignant
      small round cell tumor was determined. The clinical diagnosis was leukemia or
      lymphoma. The cytoplasmic CD20 expression was shown on the tumor cells of the
      mediastinal tru-cut biopsy. Rhabdomyosarcoma was diagnosed by the flow    
      cytometric analysis and immunohistochemical demonstration of muscle markers.    
      Rhabdomyosarcomas are traditionally distinguished from lymphomas by their    
      absence of lymphoid markers such as CD20. But in this case we have encountered   
      CD20 expression in the tumor cells. This finding lead us to conclude that the   
      presence of a lymphoid phenotype does not absolutely exclude the diagnosis of   
      rhabdomyosarcoma.

PMID- 23011832
TI  - Polymorphous low-grade adenocarcinoma located in the maxillary sinus.
AB  - Polymorphous low-grade adenocarcinoma is a malignant epithelial tumour with low  
      metastatic rate and infiltrative growth pattern. The palate is the most common 
      site. Paranasal sinuses are uncommon venues for polymorphous low-grade    
      adenocarcinoma. Here, we report a polymorphous low-grade adenocarcinoma case of  
      the maxillary sinus, a very rare location. Although it is a low grade    
      malignancy, progression may develop after a long time. Therefore, polymorphous   
      low-grade adenocarcinoma should be kept in mind in the differential diagnosis   
      even in rare sites in the head and neck.

PMID- 23011833
TI  - Adenocarcinoma arising in warthin tumor of the parotid gland.
AB  - Warthin tumor is a well-defined benign salivary gland neoplasm consisting of    
      both epithelial and lymphoid components. The tumor is the second most common    
      benign tumor next to pleomorphic adenoma. We present a case of adenocarcinoma,   
      not otherwise classified, arising in unilateral Warthin tumor of the parotid    
      gland in a 63-year-old male patient. Carcinomas arising in or from the    
      epithelial component of a preexisting parotid Warthin tumor are rare and    
      differential diagnosis of metastasis from an adenocarcinoma in Warthin tumor is  
      important. The patient underwent a complete and thorough work-up, and no other 
      primary malignant lesion was found. No other primary malignant lesion had    
      manifested at the last one year follow-up period.

PMID- 23011834
TI  - Pulmonary alveolar microlithiasis with homozygous c.316G > C (p.G106R) mutation:
      a case report.
AB  - Pulmonary alveolar microlithiasis is characterized by the presence of    
      calcospherites in alveolar spaces. Sporadic cases are more common, but the    
      disease also presents in an inherited familial form. The greatest number of    
      reported cases is from Europe and especially Turkey. We present a 43-year-old    
      female with complaints of dyspnea for many years. She had a suspicious familial  
      history of pulmonary alveolar microlithiasis. The surgical lung biopsy specimen
      appeared gritty and firm. Histological sections showed diffuse involvement of
      the lung parenchyma by innumerable tiny calcospherites. Genetic studies
      showed a     homozygous c.316G > C (p.G106R) mutation in exon 4 and confirmed the
      diagnosis of pulmonary alveolar microlithiasis. The present report aims to   
      contribute to the literature with a pathologically and genetically confirmed new
      case to add insight into the etiology of this rare disease. This case
      confirms     an autosomal recessive inheritance and does not support the role of
      non-genetic     and other factors in the pathogenesis of pulmonary alveolar
      microlithiasis.

PMID- 23011835
TI  - Primary lymphoepithelioma-like carcinoma of the lung: report of a rare case and
      review of the literature.
AB  - Primary lymphoepithelioma-like carcinoma of the lung is a rare type of non-small 
      cell lung carcinoma. In this study, we aimed to present a 62-year-old smoker  
      male with a primary lymphoepithelioma-like carcinoma of the hilar region of the
      left lung. The patient underwent left pneumonectomy and no adjuvant therapy
      was     given. There were no other abnormalities on whole body PET/CT scan
      including the     nasopharyngeal region. The patient showed seropositivity for
      EBV IgG but     immunohistochemistry and PCR amplification studied on paraffin
      embedded tissue     sections of the tumor failed to show any sign of EBV
      infection within the tumor     cells. He is alive and disease-free four months
      after the operation. Although     primary lymphoepithelioma-like carcinoma of the
      lung is usually reported in     young females with no history of tobacco use and
      the tumor cells are infected     with EBV, it may rarely be seen in elderly males
      with a history of tobacco use     and the tumor cells not infected with EBV.

PMID- 23011836
TI  - Intussusception of the appendix induced by sessile serrated adenoma: a case
      report.
AB  - Intussusception of the appendix vermiformis is a rare condition. It occurs    
      mainly in infants and children. Here, we report an intussusception case that    
      occurred in a 65-year-old male presenting with repeated periumbilical pain,    
      nausea, vomiting and febrile sensation. The appendix was seen to be    
      intussuscepted at laparoscopy. The invaginated segment was reducted and simple   
      appendicectomy was carried out. Histopathologic examination revealed a sessile  
      serrated adenoma at the wall of the appendix, suggesting it as the cause of the
      intussusception.

PMID- 23011837
TI  - Mixture of three amino acids as stabilizers replacing albumin in lyophilization
      of new third generation recombinant factor VIII GreenGene F.
AB  - A formulation with stabilizers replacing albumin was developed for lyophilization
      of recombinant factor VIII (FVIII), GreenGene F (WHO INN: beroctocog alfa), to
      achieve stability and eliminate safety issues of blood-derived albumin. L
      Arginine (hydrophilic amino acid, positively charged side chain), L-glutamic acid
      (hydrophilic amino acid, negatively charged side chain), and L-isoleucine
      (hydrophobic amino acid, nonpolar) were selected as stabilizers, and the mixture
      of the three amino acids were optimized. The mixture had results comparative with
      albumin and other commonly used stabilizers showing good preservation of
      recombinant FVIII during lyophilization, robust stability with consistently high
      recovery of FVIIII, very low aggregate formation, and good storage stability
      without alterations in protein characteristics. In vivo test results showed that
      the efficacy was maintained and had no signs of toxicity. The study demonstrated
      that the three amino acid mixture acts as a good stabilizer for lyophilization of
      recombinant FVIII and as a safe excipient.

PMID- 23011838
TI  - Solution NMR structure of a sheddase inhibitor prodomain from the malarial
      parasite Plasmodium falciparum.
AB  - Plasmodium subtilisin 2 (Sub2) is a multidomain protein that plays an important
      role in malaria infection. Here, we describe the solution NMR structure of a
      conserved region of the inhibitory prodomain of Sub2 from Plasmodium falciparum,
      termed prosub2. Despite the absence of any detectable sequence homology, the
      protozoan prosub2 has structural similarity to bacterial and mammalian subtilisin
      like prodomains. Comparison with the three-dimensional structures of these other
      prodomains suggests a likely binding interface with the catalytic domain of Sub2
      and provides insights into the locations of primary and secondary processing
      sites in Plasmodium prodomains.

PMID- 23011839
TI  - Increased GTP cyclohydrolase activity promotes tumor growth.

PMID- 23011840
TI  - Auto-threshold quantification of late gadolinium enhancement in patients with
      acute heart disease.
AB  - PURPOSE: To assess the Otsu-Auto-Threshold (OAT) for accuracy and reproducibility
      for sizing irreversible injury in late gadolinium enhancement (LGE) images of
      patients with acute heart disease. The OAT method automatically identifies high
      signal intensity areas using a cutoff derived from the signal intensity histogram
      and therefore is user-independent. MATERIALS AND METHODS: LGE was performed in 28
      patients with acute myocardial infarction (MI) and 30 patients with acute
      myocarditis. LGE mass was compared between OAT and thresholds using 2 standard
      deviations (SD), 3SD, and 5SD above remote myocardium, and full-width-at-half
      maximum (FWHM). A separate, blinded visual assessment served as the standard of
      truth. RESULTS: In patients with acute MI, OAT and 5SD did not differ (26.1 +/-
      11.4 g vs. 25.4 +/- 11.1 g, P = 0.088), but thresholds of 2SD and 3SD
      overestimated LGE mass by 37% and 20%, respectively, and FWHM underestimated by
      15%. In acute myocarditis, OAT was not different from a visual quantification,
      but thresholds of 2SD and 3SD overestimated LGE mass by 46% and 19%,
      respectively, and thresholds of 5SD and FWHM underestimated LGE mass by 17% and
      26%, respectively. OAT and FWHM showed the best intraobserver and interobserver
      reproducibility. CONCLUSION: Automatic thresholding using OAT may serve as an
      accurate and reproducible method to quantify irreversible myocardial injury in
      acute heart disease.

PMID- 23011842
TI  - Continuous polycrystalline zeolitic imidazolate framework-90 membranes on
      polymeric hollow fibers.
AB  - Headed for a membrane: Continuous, polycrystalline ZIF-90 membranes (picture,
      left) can be grown at 65  degrees C from methanolic precursor solutions on
      nanocrystal-seeded surfaces of poly(amide-imide) macroporous hollow fibers
      (right). The ZIF-90 membranes exhibit good separation properties for linear over
      cyclic hydrocarbons, as well as gas permeation selectivities higher than Knudsen
      values.

PMID- 23011841
TI  - Regulation of the activities of the mammalian transglutaminase family of enzymes.
AB  - Mammalian transglutaminases catalyze post-translational modifications of
      glutamine residues on proteins and peptides through transamidation or deamidation
      reactions. Their catalytic mechanism resembles that of cysteine proteases. In
      virtually every case, their enzymatic activity is modulated by elaborate
      strategies including controlled gene expression, allostery, covalent
      modification, and proteolysis. In this review, we focus on our current knowledge
      of post-translational regulation of transglutaminase activity by physiological as
      well as synthetic allosteric agents. Our discussion will primarily focus on
      transglutaminase 2, but will also compare and contrast its regulation with Factor
      XIIIa as well as transglutaminases 1 and 3. Potential structure-function
      relationships of known mutations in human transglutaminases are analyzed.

PMID- 23011843
TI  - The 2012 Chitranjan Ranawat award: intraarticular analgesia after TKA reduces
      pain: a randomized, double-blinded, placebo-controlled, prospective study.
AB  - BACKGROUND: Postoperative pain after total knee arthroplasty remains one of the
      most important challenges facing patients undergoing this surgery. Providing a
      balance of adequate analgesia while limiting the functional impact of regional
      anesthesia and minimizing opioid side effects is critical to minimize adverse
      events and improve patient satisfaction. QUESTIONS/PURPOSES: We asked whether
      bupivacaine delivered through an elastomeric device decreases the (1) patients'
      perception of pain after TKA; (2) narcotic consumption; and (3) narcotic-related
      side effects as compared with a placebo. METHODS: In this prospective, double
      blind, placebo-controlled study, all patients received standardized regional
      anesthesia, a preemptive and multimodal analgesic protocol, and a continuous
      intraarticular infusion at 5 mL/hour through an elastomeric infusion pump. The
      patients were randomized to receive either an infusion pump filled with (1) 300
      mL of 0.5% bupivacaine, the experimental group (n = 75); or (2) 300 mL of 0.9%
      normal saline solution, the control group (n = 75). Data concerning postoperative
      pain levels through a visual analog scale, postoperative opioid consumption,
      opioid-related side effects, and complications were collected and analyzed.
      RESULTS: Patients in the experimental group receiving the bupivacaine reported a
      reduction in pain levels in highest, lowest, and current visual analog scale
      scores compared with the placebo group on the first postoperative day and highest
      visual analog scale score on postoperative Day 2 along with a 33% reduction in
      opioid consumption on postoperative Day 2 and a 54% reduction on postoperative
      Day 3. CONCLUSION: In patients undergoing TKA, continuous intraarticular
      analgesia provided an effective adjunct for pain relief in the immediate
      postoperative period without the disadvantages encountered with other analgesic
      methods.

PMID- 23011844
TI  - Lipid-functionalized dextran nanosystems to overcome multidrug resistance in
      cancer: a pilot study.
AB  - BACKGROUND: The toxicity of anticancer agents and the difficulty in delivering
      drugs selectively to tumor cells pose a challenge in overcoming multidrug
      resistance (MDR). Recently, nanotechnology has emerged as a powerful tool in
      addressing some of the barriers to drug delivery, including MDR in cancer, by
      utilizing alternate routes of cellular entry and targeted delivery of drugs and
      genes. However, it is unclear whether doxorubicin (Dox) can be delivered by
      nanotechnologic approaches. QUESTIONS/PURPOSES: We asked whether (1) Dox-loaded
      lipid-functionalized dextran-based biocompatible nanoparticles (Dox/NP) can
      reverse MDR, (2) Dox/NP has more potent cytotoxic effect on MDR tumors than
      poly(ethylene glycol)-modified liposomal Dox (PLD), and (3) multidrug resistance
      protein 1 (MDR1) small interfering RNA loaded in these nanoparticles (siMDR1/NP)
      can modulate MDR. METHODS: To create stable Dox/NP and siMDR1/NP, we used two
      different lipid-modified dextran derivatives. The effect of Dox or Dox/NP was
      tested on drug-sensitive osteosarcoma (KHOS) and ovarian cancer (SKOV-3) cell
      cultures in triplicate and their respective MDR counterparts KHOS(R2) and SKOV
      3(TR) in triplicate. We determined the effects on drug retention, transfection
      efficacy of siMDR1/NP, and P-glycoprotein expression and the antiproliferative
      effect between Dox/NP and PLD in MDR tumor cells. RESULTS: Fluorescence
      microscopy revealed efficient uptake of the Dox/NP and fluorescently tagged
      siMDR1/NP. Dox/NP showed five- to 10-fold higher antiproliferative activity at
      the 50% inhibitory concentration than free Dox in tumor cells. Dox/NP showed
      twofold higher activity than PLD in MDR tumor cells. siMDR1/NP (100 nM)
      suppressed P-glycoprotein expression in KHOS(R2). CONCLUSIONS: Dextran-lipid
      nanoparticles are a promising platform for delivering Dox and siRNAs. CLINICAL
      RELEVANCE: Biocompatible dextran-based nanoparticles that are directly
      translatable to clinical medicine may lead to new potential therapeutics for
      reversing MDR in patients with cancer.

PMID- 23011845
TI  - Femoral lateral bowing and varus condylar orientation are prevalent and affect
      axial alignment of TKA in Koreans.
AB  - BACKGROUND: Coronal alignment is considered key to the function and longevity of
      a TKA. However, most studies do not consider femoral and tibial anatomical
      features such as lateral femoral bowing and the effects of these features and
      subsequent alignment on function after TKA are unclear. QUESTIONS/PURPOSES: We
      therefore determined (1) the prevalence of lateral femoral bowing, varus femoral
      condylar orientation, and severe tibia plateau inclination in female Koreans
      undergoing TKA; (2) whether postoperative alignments are affected by these
      anatomical features and improved by the use of navigation; and (3) whether
      postoperative coronal alignments are associated with function. METHODS: We
      measured alignment in 367 knees that underwent TKA and 60 sex- and age-matched
      normal knees (control group). We determined patterns and degrees of femoral
      bowing angle, femoral condylar orientation, and tibial plateau inclination on
      preoperative full-limb radiographs. Postoperatively, coronal alignment of limbs
      and of femoral and tibial components was measured. We compared American Knee
      Society scores, WOMAC scores, and SF-36 scores in aligned knees and outliers
      (beyond +/- 3 degrees  or +/- 2 degrees ) at 1 year. RESULTS: The prevalence of
      lateral femoral bowing was 88% in the TKA group and 77% in the control group.
      Mean femoral condylar orientation angle was varus 2.6 degrees  in the TKA group
      and valgus 1.1 degrees  in the control group, and mean tibial plateau inclination
      was varus 8.3 degrees  in the TKA group and varus 5.4 degrees  in the control
      group. Femoral lateral bowing and varus femoral condylar orientation were
      associated with postoperative alignments. Several clinical outcome scales were
      inferior in the outliers in mechanical tibiofemoral angle, anatomical
      tibiofemoral angle, and tibial coronal alignment but not in femoral coronal
      alignment outliers. CONCLUSIONS: Lateral femoral bowing, varus condylar
      orientation, and severe varus inclination of the tibia plateau should be
      considered when performing TKA in Korean patients or patients with otherwise
      similar anatomical features.

PMID- 23011846
TI  - Structural basis of heparan sulfate-specific degradation by heparinase III.
AB  - Heparinase III (HepIII) is a 73-kDa polysaccharide lyase (PL) that degrades the
      heparan sulfate (HS) polysaccharides at sulfate-rare regions, which are important
      co-factors for a vast array of functional distinct proteins including the well
      characterized antithrombin and the FGF/FGFR signal transduction system. It
      functions in cleaving metazoan heparan sulfate (HS) and providing carbon,
      nitrogen and sulfate sources for host microorganisms. It has long been used to
      deduce the structure of HS and heparin motifs; however, the structure of its own
      is unknown. Here we report the crystal structure of the HepIII from Bacteroides
      thetaiotaomicron at a resolution of 1.6 A. The overall architecture of HepIII
      belongs to the (alpha/alpha)5 toroid subclass with an N-terminal toroid-like
      domain and a C-terminal beta-sandwich domain. Analysis of this high-resolution
      structure allows us to identify a potential HS substrate binding site in a tunnel
      between the two domains. A tetrasaccharide substrate bound model suggests an
      elimination mechanism in the HS degradation. Asn260 and His464 neutralize the
      carboxylic group, whereas Tyr314 serves both as a general base in C-5 proton
      abstraction, and a general acid in a proton donation to reconstitute the terminal
      hydroxyl group, respectively. The structure of HepIII and the proposed reaction
      model provide a molecular basis for its potential practical utilization and the
      mechanism of its eliminative degradation for HS polysaccarides.

PMID- 23011847
TI  - Conservation through connectivity: can isotopic gradients in Africa reveal winter
      quarters of a migratory bird?
AB  - Conservation of migratory wildlife requires knowledge of migratory connectivity
      between breeding and non-breeding locations. Stable isotopes in combination with
      geographical isotopic patterns (isoscapes) can provide inferences about migratory
      connectivity. This study examines whether such an approach can be used to infer
      wintering areas in sub-Saharan Africa, where we lack such knowledge for many
      species, but where this method has not been used widely. We measured delta (2)H,
      delta (13)C and delta (15)N in winter-grown feathers of a breeding Swiss and
      Spanish population of European hoopoe Upupa epops--a typical Palaearctic
      Afrotropical migrant. delta (2)H values predicted that ~70 % of the hoopoes spent
      the non-breeding season in the western portion of their potential winter range.
      This was corroborated by a shallow east-west gradient in feather-delta (2)H
      values of museum specimens from known African origin across the potential winter
      range and by the recovery of Swiss hoopoes marked with geolocators. Hoopoes
      categorized as from eastern versus western regions of the wintering range were
      further delineated spatially using feather delta (13)C and delta (15)N. delta
      (15)N showed no trend, whereas adults were more enriched in (13)C in the western
      portion of the range, with eastern adults being in addition more depleted in
      (13)C than eastern juveniles. This suggests that eastern juveniles may have
      occupied more xeric habitats than sympatric adults. We demonstrated that stable
      isotopes, especially delta (2)H, could only very roughly delineate the winter
      distribution of a trans-Saharan Palaearctic migrant restricted primarily to the
      Sahelian and savanna belt south of the Sahara. Further refinements of
      precipitation isoscapes for Africa as well the development of isoscapes for delta
      (13)C and delta (15)N may improve assignment of this and other migrants.

PMID- 23011848
TI  - Clutch identity and predator-induced hatching affect behavior and development in
      a leaf-breeding treefrog.
AB  - For species with complex life cycles, transitions between life stages result in
      niche shifts that are often associated with evolutionary trade-offs. When
      conditions across life stages are unpredictable, plasticity in niche shift timing
      may be adaptive; however, factors associated with clutch identity (e.g., genetic
      or maternal) may influence the effects of such plasticity. The red-eyed treefrog
      (Agalychnis callidryas) is an ideal organism for investigating the effects of
      genetics and life stage switch point timing because embryos exhibit adaptive
      phenotypic plasticity in hatching time. In this study, we evaluated the effects
      of experimentally manipulated hatching time and clutch identity on antipredator
      behavior of tadpoles and on developmental traits of metamorphs, including larval
      period, mass, SVL, and jumping ability. We found that in the presence of
      dragonfly nymph predator cues at 21 days post-oviposition, tadpoles reduced both
      their activity level and height in the water column. Furthermore, early-hatched
      tadpoles were less active than late-hatched tadpoles of the same age. This
      difference in behavior patterns of early- and late-hatched tadpoles may represent
      an adaptive response due to a longer period of susceptibility to odonate
      predators for early-hatched tadpoles, or it may be a carry-over effect mediated
      by early exposure to an environmental stressor (i.e., induction of early
      hatching). We also found that hatching time affected both behavioral traits and
      developmental traits, but its effect on developmental traits varied significantly
      among clutches. This study shows that a single early-life event may influence a
      suite of factors during subsequent life stages and that some of these effects
      appear to be dependent on clutch identity. This interaction may represent an
      evolutionary response to a complex life cycle and unpredictable environments,
      regardless of whether the clutch differences are due to additive genetic variance
      or maternal effects.

PMID- 23011850
TI  - Nutritional status of Abies pinsapo forests along a nitrogen deposition gradient:
      do C/N/P stoichiometric shifts modify photosynthetic nutrient use efficiency?
AB  - Chronic atmospheric N deposition has modified relative N availability, altering
      the biogeochemical cycles of forests and the stoichiometry of nutrients in trees,
      inducing P limitation, and modifying the N:P ratios of plant biomass. This study
      examines how the variation in the foliar stoichiometry of Abies pinsapo across an
      N deposition gradient affects foliar traits and photosynthetic rate. We measured
      the maximum net assimilation rates (Amax) and the foliar nitrogen (N) and
      phosphorus (P) concentrations in A. pinsapo needles of five age classes. The leaf
      mass per area and photosynthetic N and P use efficiencies (PNUE and PPUE,
      respectively) were also estimated. The results from the N-saturated stand (Sierra
      Bermeja, B) differed from the comparable N-limited stands under investigation
      (Yunquera, Y, and Sierra Real, SR). The trees from Y and SR exhibited a reduction
      in the N content in older needles, whereas the foliar N concentration at the B
      site increased with needle age. N and P were positively correlated at Y and SR,
      but not at B, suggesting that the overload of N in the trees at site B has
      exceeded the homeostatic regulation capacity of the N-saturated stand in terms of
      foliar stoichiometry. A max and PNUE were correlated positively with P and
      negatively with the N/P ratio at the three study sites. The foliar N
      concentration was positively correlated with A max at Y and SR. However, this
      relationship was negative for the B site. These findings suggest that the
      nutritional imbalance caused by increased chronic deposition of N and an
      insufficient supply of P counteracts the potential increase in net photosynthesis
      induced by the accumulation of foliar N.

PMID- 23011849
TI  - Chasing the Patagonian sun: comparative thermal biology of Liolaemus lizards.
AB  - The importance of the thermal environment for ectotherms and its relationship
      with thermal physiology and ecology is widely recognized. Several models have
      been proposed to explain the evolution of the thermal biology of ectotherms, but
      experimental studies have provided mixed support. Lizards from the Liolaemus
      goetschi group can be found along a wide latitudinal range across Argentina. The
      group is monophyletic and widely distributed, and therefore provides excellent
      opportunities to study the evolution of thermal biology. We studied thermal
      variables of 13 species of the L. goetschi group, in order to answer three
      questions. First, are aspects of the thermal biology of the L. goetschi group
      modelled by the environment or are they evolutionarily conservative? Second, have
      thermal characteristics of these animals co-evolved? And third, how do the
      patterns of co-evolution observed within the L. goetschi group compare to those
      in a taxonomically wider selection of species of Liolaemus? We collected data on
      13 focal species and used species information of Liolaemus lizards available in
      the literature and additional data obtained by the authors. We tackled these
      questions using both conventional and phylogenetically based analyses. Our
      results show that lizards from the L. goetschi group and the genus Liolaemus in
      general vary in critical thermal minimum in relation to mean air temperature, and
      particularly the L. goetschi group shows that air temperature is associated with
      critical thermal range, as well as with body temperature. Although the effect of
      phylogeny cannot be ignored, our results indicate that these thermal biology
      aspects are modelled by cold environments of Patagonia, while other aspects
      (preferred body temperature and critical thermal maximum) are more conservative.
      We found evidence of co-evolutionary patterns between critical thermal minimum
      and preferred body temperature at both phylogenetic scales (the L. goetschi group
      and the extended sample of 68 Liolaemus species).

PMID- 23011851
TI  - Activated chemical defenses suppress herbivory on freshwater red algae.
AB  - The rapid life cycles of freshwater algae are hypothesized to suppress selection
      for chemical defenses against herbivores, but this notion remains untested.
      Investigations of chemical defenses are rare for freshwater macrophytes and
      absent for freshwater red algae. We used crayfish to assess the palatability of
      five freshwater red algae relative to a palatable green alga and a chemically
      defended aquatic moss. We then assessed the roles of structural, nutritional, and
      chemical traits in reducing palatability. Both native and non-native crayfish
      preferred the green alga Cladophora glomerata to four of the five red algae.
      Batrachospermum helminthosum, Kumanoa holtonii, and Tuomeya americana employed
      activated chemical defenses that suppressed feeding by 30-60 % following damage
      to algal tissues. Paralemanea annulata was defended by its cartilaginous
      structure, while Boldia erythrosiphon was palatable. Activated defenses are
      thought to reduce ecological costs by expressing potent defenses only when
      actually needed; thus, activation might be favored in freshwater red algae whose
      short-lived gametophytes must grow and reproduce rapidly over a brief growing
      season. The frequency of activated chemical defenses found here (three of five
      species) is 3-20* higher than for surveys of marine algae or aquatic vascular
      plants. If typical for freshwater red algae, this suggests that (1) their
      chemical defenses may go undetected if chemical activation is not considered and
      (2) herbivory has been an important selective force in the evolution of
      freshwater Rhodophyta. Investigations of defenses in freshwater rhodophytes
      contribute to among-system comparisons and provide insights into the generality
      of plant-herbivore interactions and their evolution.

PMID- 23011852
TI  - Spatial and temporal variation in survival of a rare reptile: a 22-year study of
      Sonoran desert tortoises.
AB  - Although many species may be vulnerable to changes in climate, forecasting
      species-level responses can be challenging given the array of physiological,
      behavioral, and demographic attributes that might be affected. One strategy to
      improve forecasts is to evaluate how species responded to climatic variation in
      the past. We used 22 years of capture-recapture data for Sonoran desert tortoises
      (Gopherus morafkai) collected from 15 locations across their geographic range in
      Arizona to evaluate how environmental factors affected spatial and temporal
      variation in survival. Although rates of annual survival were generally high
      ([Formula: see text] = 0.92), survival of adults decreased with drought severity,
      especially in portions of their range that were most arid and nearest to cities.
      In three locations where large numbers of carcasses from marked tortoises were
      recovered, survival of adults was markedly lower during periods of severe drought
      ([Formula: see text] = 0.77-0.81) compared to all other periods ([Formula: see
      text] = 0.93-0.98). Assuming continued levels of dependency of humans on fossil
      fuels, survival of adult tortoises is predicted to decrease by an average of 3 %
      during 2035-2060 relative to survival during 1987-2008 in 14 of the 15
      populations we studied. This decrease could reduce persistence of tortoise
      populations, especially in arid portions of their range. Temporal and spatial
      variation in drought conditions are important determinants of survival in adult
      desert tortoises.

PMID- 23011853
TI  - Catalytic, asymmetric halofunctionalization of alkenes--a critical perspective.
AB  - Despite the fact that halogenation of alkenes has been known for centuries,
      enantioselective variants of this reaction have only recently been developed. In
      the past three years, catalytic enantioselective versions of
      halofunctionalizations with the four common halogens have appeared and although
      important breakthroughs, they represent just the very beginnings of a nascent
      field. This Minireview provides a critical analysis of the challenges that
      accompany the development of general and highly enantioselective
      halofunctionalization reactions. Moreover, the focus herein, diverges from
      previous reviews of the field by identifying the various modes of catalysis and
      the different strategies implemented for asymmetric induction.

PMID- 23011854
TI  - The role of annexin A3 playing in cancers.
AB  - Annexin family proteins are a well-known multigene family of Ca(2+)-regulated
      phospholipid- and membrane-binding proteins. As one of the annexin family
      genes/proteins, accumulated researches have begun to reveal that annexin A3
      (Anxa3) exhibits important roles in tumor development, metastasis and drug
      resistance. The summarized research evidences in recent years indicate Anxa3
      might specifically functionalize either as a tumor suppressor or as a tumor
      promoter candidate for different cancers depending on the types of tumor cells
      and tissues. The up-regulation of Anxa3 was found to be correlated with enhanced
      drug resistance of ovarian cancer, to promote the developments of colorectal
      adenocarcinoma and pancreatic carcinoma, and to facilitate the metastases of lung
      adenocarcinoma and hepatocarcinoma; meanwhile, the decreased Anxa3 expressions
      was negatively correlated with the developments of prostatic carcinoma and renal
      carcinoma. It is conceivable that Anxa3 could be regarded as a target for
      therapeutic intervention and a biological indicator for tumor development,
      invasion and metastasis as well as for the prognosis of tumor patients.

PMID- 23011855
TI  - Lethal mutations in the major homology region and their suppressors act by
      modulating the dimerization of the rous sarcoma virus capsid protein C-terminal
      domain.
AB  - An infective retrovirus requires a mature capsid shell around the viral
      replication complex. This shell is formed by about 1500 capsid protein monomers,
      organized into hexamer and pentamer rings that are linked to each other by the
      dimerization of the C-terminal domain (CTD). The major homology region (MHR), the
      most highly conserved protein sequence across retroviral genomes, is part of the
      CTD. Several mutations in the MHR appear to block infectivity by preventing
      capsid formation. Suppressor mutations have been identified that are distant in
      sequence and structure from the MHR and restore capsid formation. The effects of
      two lethal and two suppressor mutations on the stability and function of the CTD
      were examined. No correlation with infectivity was found for the stability of the
      lethal mutations (D155Y-CTD, F167Y-CTD) and suppressor mutations (R185W-CTD,
      I190V-CTD). The stabilities of three double mutant proteins (D155Y/R185W-CTD,
      F167Y/R185W-CTD, and F167Y/I190V-CTD) were additive. However, the dimerization
      affinity of the mutant proteins correlated strongly with biological function. The
      CTD proteins with lethal mutations did not dimerize, while those with suppressor
      mutations had greater dimerization affinity than WT-CTD. The suppressor mutations
      were able to partially correct the dimerization defect caused by the lethal MHR
      mutations in double mutant proteins. Despite their dramatic effects on
      dimerization, none of these residues participate directly in the proposed
      dimerization interface in a mature capsid. These findings suggest that the
      conserved sequence of the MHR has critical roles in the conformation(s) of the
      CTD that are required for dimerization and correct capsid maturation.

PMID- 23011856
TI  - [Botulinum toxin A in chronic refractory migraine: premarketing experience].
AB  - INTRODUCTION: Chronic migraine is very disabling, with medication overuse
      commonly associated. The recent approval of botulinum toxin-A -OnabotulinumtoxinA
      (OnabotA)- means a hallmark. AIM: To describe our experience in compassionate use
      before approval. PATIENTS AND METHODS: 35 cases with chronic migraine assessed
      between July 2009-December 2011 in a specialized headache consultation. 100 U of
      OnabotA were injected in 21 points over the facial and pericranial muscles,
      according to a modified PREEMPT protocol. We determined before and after
      treatment: number of episodes and migraine days; pain intensity and days of
      disability extracted from MIDAS score, and data regarding drug intake. After
      follow-up, new injections were given at intervals dictated by individualized
      response timing. Therapeutic response was considered when: intensity of pain was
      reduced to a half o >= 4 VAS points, or the number of monthly days of pain
      descended >= 7/month, or the case converted to non-drug overuser. RESULTS: In 27
      cases (80%) it was proved clinical improvement. This effect was confirmed by: a
      reduction in headache severity, reflected as much in pain intensity (VAS scale <
      0.001) as in the number of days with disability (3.2 vs 0.4, p < 0.001); an
      improvement in the number of monthly days of pain (19.8 vs 13.8, p < 0.05; a
      significant decrease in the number of cases of medication overuse (69% vs 13%, p
      < 0.01). Mean duration of effect was 15 weeks and mean follow-up 9.8 months.
      CONCLUSIONS: OnabotA disclosed efficacy as prophylactic treatment of chronic
      migraine. It is mainly expressed as a reduction of pain intensity. Medication
      overuse also descended. Adverse events were sparse.

PMID- 23011857
TI  - [Clinical profile in subjects with acquired brain injury in chronic phase in a
      social and health care center].
AB  - INTRODUCTION: There are few resources for acquired brain injury (ABI) in post
      hospitalary phase in our country. At this level of carefulness, Personal Autonomy
      Promotion Center in Bergondo contemplates like a social and health care resource
      in order to facilitate community integration in subjects with ABI. AIMS. To
      describe clinical profile in the subjects admitted in our unit, and to assess
      intervention possibilities with clinico-functional recovery goals in the chronic
      phases in ABI. PATIENTS AND METHOD: . Sample of 105 subjects admitted in our
      center until December 2010. 86 men and 19 women, with a mean age of 32.16 years
      old and a most frequent evolution time of less than 5 years (64.76%). Variables
      collected were: sex, age, etiology, evolution time, personality changes
      diagnosis, admission FIM, previous participation in rehabilitation programmes and
      have recovery goals. RESULTS: The main etiology was traumatic brain injury
      (62.5%). The 54.28% of the subjects was taking physical rehabilitation at the
      moment of admission, while the 49.52% had participated in neuropsychological
      interventions. Physical recovery goals were identified in the 42.85% of the
      subjects and the 78.09% had goals in neuropsychology field. CONCLUSION: The
      clinical profile observed was young man with sequelae caused by a traumatic brain
      injury suffered in last five years, who has received poor neuropsychological care
      and that still takes physiotherapy treatment.

PMID- 23011858
TI  - [A new shortened version of the Boston Naming Test for those aged over 65: an
      approach from item response theory].
AB  - INTRODUCTION: One of the tests that is mostly widely used to evaluate aphasia in
      clinical practice is the Boston Naming Test (BNT), a classic test in which 60
      black and white pictures are presented to subjects in order to evaluate their
      capacity to put a name to such pictures. Despite its psychometric goodness, the
      number of items in the test has to be reduced in order to lower the time required
      to apply it. SUBJECTS AND METHODS: Researchers recruited a sample of 547 subjects
      over the age of 65, who were then administered a neuropsychological evaluation
      protocol, including the BNT, to determine their cognitive statuses. No relevant
      cognitive alterations were observed in 405 subjects versus 142 who were diagnosed
      with mild cognitive impairment. RESULTS: The number of items was reduced in
      accordance with the premises of the item response theory. Since both age and
      level of schooling were found to have a significant effect on performance in the
      test, the two variables were used to find the cut-off points of the shortened
      version. This new version presented an adequate degree of reliability (alpha =
      0.765) and a high correlation with the original test (r = 0.876). CONCLUSIONS:
      The new shortened version consists of 15 items that are ordered according to the
      degree of difficulty. It is a task with a high level of discriminating power that
      is useful in day-to-day clinical practice for detecting alterations in the
      language of the elderly.

PMID- 23011859
TI  - [Response to treatment with corticoids in a case of inflammatory amyloid
      angiopathy without performing a biopsy].
AB  - INTRODUCTION: Inflammatory amyloid angiopathy (IAA) is an infrequent presenting
      symptom of the recently recognised cerebral amyloid angiopathy and its definitive
      diagnosis is reached by means of pathological analyses. AIM: We report the case
      of a male patient with IAA and good clinical, neuropsychological and neuroimaging
      response to treatment with corticoids; a biopsy of brain tissue was not
      considered necessary. CASE REPORT: The patient, 68 years old and diagnosed with
      Alzheimer's disease, suffered from generalised seizures followed by a language
      disorder and hemiparesis of the right-hand side. A magnetic resonance imaging
      scan showed a lesion displaying infiltrating behaviour in the left hemisphere and
      multiple instances of microbleeding. Clinical and radiological features suggested
      IAA and treatment was established with corticoids. Neuroimaging and
      neuropsychological tests revealed a notable improvement at 30 days after
      beginning treatment with immunosuppressants. The genotype was ApoE e4/e4. The
      need to perform a biopsy of brain tissue was ruled out. CONCLUSIONS: The case
      described here suggests that, in individualised cases with clinical and
      radiological features that are characteristic of IAA, it may be possible to
      establish an empirical treatment with corticoids with a probability diagnosis and
      perform a biopsy of brain tissue in the event of a lack of response to treatment.

PMID- 23011860
TI  - [Adenosine and homeostatic control of sleep. Actions in target structures of the
      sleep-wake circuits].
AB  - Sleep homeostasis occurs during prolonged wakefulness. Drowsiness and sleep
      pressure are its behavioral manifestations and, when sleep is allowed, there is a
      sleep rebound of sufficient duration and intensity to compensate for the previous
      deprivation. Adenosine is one of the molecules involved in sleep homeostasic
      regulation. Caffeine and theophylline, stimulants widely consumed by the humans,
      are antagonists. It is an endogenous factor, resulting from ATP metabolism in
      neurons and glia. Adenosine accumulates in the extracellular space, where it can
      exert regulatory actions on the sleep-wakefulness cycle circuits. Adenosine acts
      through the purinergic receptors A1 and A2. This paper reviews: 1) the metabolic
      pathways of cerebral adenosine, and the mechanisms of its release by neurons and
      glia to the extracellular space; 2) the actions of adenosine and its antagonists
      in regions of the central nervous system related to wakefulness, non-REM sleep,
      and REM sleep, and 3) the synaptic mechanisms involved in these actions.

PMID- 23011861
TI  - [Treatment of spasticity in multiple sclerosis: new perspectives regarding the
      use of cannabinoids].
AB  - Spasticity remains a prevalent symptom in multiple sclerosis, with a significant
      associated disability and quality of life impairment. A significant improvement
      in therapy aimed at reducing multiple sclerosis relapses and modifying its course
      has been achieved in recent years. Both general and specific traditional
      treatments have, however, major limitations. Thus, its use in real practice is
      lower than expected. Cannabinoids provide a new way for therapy. A delta-9
      tetrahydrocannabinol plus cannabidiol (1:1) association, administered through an
      oromucosal route, has been approved in several countries including Spain; it
      causes a specific effect on CB(1) and CB(2) receptors, with traditional
      psychotropic cannabis actions being minimized. Randomized, placebo-controlled
      trials, as well as longer-term open-label extensions, have shown a clear-cut
      efficacy to reduce spasticity and their associated symptoms in those patients
      refractory to other therapies, with a good tolerability/safety profile. No
      tolerance, abuse or addictive issues have been found. New studies will be needed
      to find out potential new cannabinoid-related therapies.

PMID- 23011862
TI  - [Epilepsy in literature, cinema and television].
AB  - INTRODUCTION: Literature, cinema and television have often portrayed
      stereotypical images of people that have epilepsy and have helped foster false
      beliefs about the disease. AIM: To examine the image of epilepsy presented by
      literature, cinema and television over the years. DEVELOPMENT: Epilepsy has
      frequently been portrayed in literary works, films and television series, often
      relating it with madness, delinquency, violent behaviours or possession by the
      divine or the diabolical, all of which has helped perpetuate our ancestral
      beliefs. The literary tales and the images that appear in films and on television
      cause an important emotional impact and, bearing in mind that many people will
      only ever see an epileptic seizure in a film or in a TV series or might gain some
      information about the disorder from a literary text, what they see on the screen
      or read in the novels will be their only points of reference. Such experiences
      will therefore mark the awareness and knowledge they will have about epilepsy and
      their attitudes towards the people who suffer from it. Novels and films are
      fiction, but it is important to show realistic images of the disease that are no
      longer linked to the false beliefs of the past and which help the general public
      to have a more correct view of epilepsy that is free from prejudices and
      stereotypes. CONCLUSIONS: Literature, cinema and television have often dealt with
      the subject of epilepsy, sometimes realistically, but in many cases they have
      only helped to perpetuate false beliefs about this disease.

PMID- 23011864
TI  - Genital sensory aura in migraine.

PMID- 23011865
TI  - [Usefulness of neurosonology in the diagnosis of acute hydrocephalus. Reply].

PMID- 23011866
TI  - [Cardioembolic stroke in atrial fibrillation and new anticoagulation criteria: a
      therapeutic dare].

PMID- 23011867
TI  - Hydrodynamic characteristics and microalgae cultivation in a novel flat-plate
      photobioreactor.
AB  - Flat-plate photobioreactors (FPPBRs) are widely reported for cultivation of
      microalgae. In this work, a novel FPPBR mounted with inclined baffles was
      developed, which can make the fluid produce a "spirality" flow. The flow field
      and cell trajectory in the photobioreactor were investigated by using
      computational fluid dynamics. In addition, the cell trajectory was analyzed using
      a Fast Fourier transformation. The influence of height of the baffles, the angle
      alpha between the inclined baffle and fluid inlet flow direction (z), and the
      fluid inlet velocity on the frequency of flashing light effect and pressure drop
      were examined to optimize the structure parameters of the inclined baffles and
      operating conditions of the photobioreactor. The results showed that with
      inclined baffles built-in, significant swirl flow could be generated in the
      FPPBR. In this way, the flashing light effect for microalgal cell could also be
      achieved and the photosynthesis efficiency of microalgae could be promoted. In
      outdoor cultivation of freshwater Chlorella sp., the maximum biomass productivity
      of Chlorella sp. cultivated in the photobioreactor with inclined baffles was
      29.94% higher than that of the photobioreactor without inclined baffles.

PMID- 23011869
TI  - The role of functionally defective rare germline variants of sialic acid
      acetylesterase in autoimmune Addison's disease.
AB  - BACKGROUND: Autoimmune Addison's disease (AAD) is a rare condition with a complex
      genetic basis. A panel of rare and functionally defective genetic variants in the
      sialic acid acetylesterase (SIAE) gene has recently been implicated in several
      common autoimmune conditions. We performed a case-control study to determine
      whether these rare variants are associated with a rarer condition, AAD. METHOD:
      We analysed nine SIAE gene variants (W48X, M89V, C196F, C226G, R230W, T312M,
      Y349C, F404S and R479C) in a United Kingdom cohort of 378 AAD subjects and 387
      healthy controls. All samples were genotyped using Sequenom iPlex chemistry to
      characterise primer extension products. RESULTS: A heterozygous rare allele at
      codon 312 (312*M) was found in one AAD patient (0.13%) but was not detected in
      the healthy controls. The commoner, functionally recessive variant at codon 89
      (89*V) was found to be homozygous in two AAD patients but was only found in the
      heterozygous state in controls. Taking into account all nine alleles examined,
      4/378 (1.06%) AAD patients and 1/387 (0.25%) healthy controls carried the
      defective SIAE alleles, with a calculated odds ratio of 4.13 (95% CI 0.44-97.45,
      two-tailed P value 0.212, NS). CONCLUSION: We demonstrated the presence of 89*V
      homozygotes and the 312*M rare allele in the AAD cohort, but overall, our
      analysis does not support a role for rare variants in SIAE in the pathogenesis of
      AAD. However, the relatively small collection of AAD patients limits the power to
      exclude a small effect.

PMID- 23011868
TI  - Clinical outcomes among HIV/tuberculosis-coinfected patients developing immune
      reconstitution inflammatory syndrome after HAART initiation in South India.
AB  - INTRODUCTION: We determine the frequency and immunological outcome of developing
      immune reconstitution inflammatory syndrome (IRIS) among HIV/tuberculosis (TB)
      coinfected Indians receiving highly active antiretroviral therapy (HAART).
      METHODS: Patients coinfected with TB and HIV who initiated HAART were classified
      based on treatment outcomes (IRIS and non-IRIS) utilizing an observational
      HIV/AIDS cohort. RESULTS: A total of 1731 HIV/TB-coinfected patients initiated
      HAART, and 95 of these patients (5.5%) developed TB-IRIS, with an incidence rate
      of 0.26 per 100 person-years. Patients who developed IRIS had significantly
      higher CD4 counts than non-IRIS patients at the time of initiating HAART, as well
      as after 6 months, 18 months, and 24 months following HAART initiation (P < .05).
      CONCLUSIONS: HIV/TB-coinfected patients who developed IRIS following HAART
      initiation had equivalent clinical outcomes compared with their HIV/TB-coinfected
      counterparts who did not develop IRIS, suggesting minimal long-term risks
      associated with IRIS.

PMID- 23011870
TI  - Bone mineral density in male adolescents with autism spectrum disorders and
      disruptive behavior disorder with or without antipsychotic treatment.
AB  - OBJECTIVE: To investigate the long-term effects of antipsychotic (AP) treatment
      and AP-induced hyperprolactinemia on bone mineral density (BMD) and body
      composition in male adolescents with autism spectrum disorders (ASDs) and/or
      disruptive behavior disorder (DBD). DESIGN: Physically healthy 10- to 20-year-old
      boys with ASD and/or DBD, chronically treated (n=56; mean 52 months, range 16-126
      months) or not treated (n=47) with an AP, were recruited to this observational
      study. Prolactin levels and biochemical bone parameters were measured and BMD of
      the lumbar spine and total body, and body composition were assessed by dual
      energy X-ray absorptiometry, and volumetric BMD of the lumbar spine calculated.
      Group differences were tested with Student's t-test, chi(2) test, Fisher exact
      test, and logistic regression analysis. RESULTS: Forty-nine percent of the boys
      treated with an AP had hyperprolactinemia. The mean volumetric lumbar spine BMD z
      score was lower (P=0.043), the total percentage of body fat z-score was higher
      (P=0.042), and biochemical bone marker carboxyterminal cross-linking telopeptide
      of bone collagen was lower in the AP-treated boys with hyperprolactinemia than in
      the AP-treated boys without hyperprolactinemia. Seven to 11% of the
      hyperprolactinemic boys had low BMD. The mean lumbar spine and total body BMD z
      scores and body composition were similar in the boys who were or were not treated
      with an AP. The total study population had a lower mean lean tissue mass (mean z
      score -0.37, P=0.004) and a higher percentage of total body fat (mean z-score
      1.16, P<0.001) than healthy controls (normative data); biochemical bone
      parameters were within normal limits. CONCLUSION: AP-induced hyperprolactinemia
      in boys with ASD or DBD may have a negative effect on lumbar spine BMD.
      Longitudinal studies are needed to confirm this finding and further disentangle
      the effects of the disorder, lifestyle, treatment, and hyperprolactinemia.

PMID- 23011871
TI  - Molecular patterns in the evolution of serrated lesion of the colorectum.
AB  - Colorectal cancer (CRC) mostly develops from a variety of polyps following mainly
      three different molecular pathways: chromosomal instability (CIN), microsatellite
      instability (MSI) and CpG island methylation (CIMP). Polyps are classified
      histologically as conventional adenomas, hyperplastic polyps, sessile serrated
      adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA). However, the
      association of these polyps with the different types of CRCs and the underlying
      genetic and epigenetic aberrations has yet to be resolved. In order to address
      this question we analyzed 140 tumors and 20 matched mucosae by array comparative
      genomic hybridization, by sequence analysis of the oncogenes BRAF, KRAS, PI3K3CA
      and by methylation arrays. MSI was tested indirectly by immunohistochemistry
      (IHC) and a loss of MLH1, MSH2, MSH6 or PMS2 was assigned as high microsatellite
      instability (MSI-H), while low microsatellite instability (MSI-L) was defined as
      MGMT IHC negativity only. CIN was detected in 78% of all MSI-H CRCs, most
      commonly as a gain of chromosome 8. Methylation data analyses allowed
      classification of samples into four groups and detected similar methylation
      profiles in SSA/P and MSI-H CRC. TSA also revealed aberrant methylation pattern,
      but clustered more heterogeneously and closer to microsatellite stable (MSS)
      CRCs. SSA/P, TSA and MSI-H CRCs had the highest degree of promotor methylation
      (CIMP pathway). Chromosomal instability, in contrast to the established doctrine,
      is a common phenomenon in MSI CRCs, yet to a lower extent and at later stages
      than in MSS CRCs. Methylation analyses suggest that SSA/P are precursors for MSI
      H CRCs and follow the CIMP pathway.

PMID- 23011872
TI  - Smooth statistical torsion angle potential derived from a large conformational
      database via adaptive kernel density estimation improves the quality of NMR
      protein structures.
AB  - Statistical potentials that embody torsion angle probability densities in
      databases of high-quality X-ray protein structures supplement the incomplete
      structural information of experimental nuclear magnetic resonance (NMR) datasets.
      By biasing the conformational search during the course of structure calculation
      toward highly populated regions in the database, the resulting protein structures
      display better validation criteria and accuracy. Here, a new statistical torsion
      angle potential is developed using adaptive kernel density estimation to extract
      probability densities from a large database of more than 106 quality-filtered
      amino acid residues. Incorporated into the Xplor-NIH software package, the new
      implementation clearly outperforms an older potential, widely used in NMR
      structure elucidation, in that it exhibits simultaneously smoother and sharper
      energy surfaces, and results in protein structures with improved conformation,
      nonbonded atomic interactions, and accuracy.

PMID- 23011873
TI  - Mutation in elongation factor G confers resistance to the antibiotic argyrin in
      the opportunistic pathogen Pseudomonas aeruginosa.
AB  - The natural myxobacterial product argyrin is a cyclic peptide exhibiting
      immunosuppressive activity as well as antibacterial activity directed against the
      highly intrinsically resistant opportunistic pathogen Pseudomonas aeruginosa. In
      this study, we used whole-genome sequencing technology as a powerful tool to
      determine the mode of action of argyrin. Sequencing of argyrin-resistant P.
      aeruginosa isolates selected in vitro uncovered six point mutations that
      distinguished the resistant mutants from their susceptible parental strain. All
      six mutations were localized within one gene: fusA1, which encodes for the
      elongation factor EF-G. After the reintroduction of selected mutations into the
      susceptible wild type, the strain became resistant to argyrin. Surface plasmon
      resonance experiments confirmed the interaction of argyrin A with FusA1.
      Interestingly, EF-G has been previously shown to be the target of the anti
      Staphylococcus antibiotic fusidic acid. Mapping of the mutations onto a
      structural model of EF-G revealed that the mutations conveying resistance against
      argyrin were clustered within domain III on the side opposite to that involved in
      fusidic acid binding, thus indicating that argyrin exhibits a new mode of protein
      synthesis inhibition. Although no mutations causing argyrin resistance have been
      found in other genes of P. aeruginosa, analysis of the sequence identity in EF-G
      and its correlation with argyrin resistance in different bacteria imply that
      additional factors such as uptake of argyrin play a role in the argyrin
      resistance of other organisms.

PMID- 23011874
TI  - Hepatocellular carcinoma in a North American population: does hepatobiliary MR
      imaging with Gd-EOB-DTPA improve sensitivity and confidence for diagnosis?
AB  - PURPOSE: To evaluate the value of hepatobiliary phase imaging for detection and
      characterization of hepatocellular carcinoma (HCC) in liver MRI with Gd-EOB-DTPA,
      in a North American population. MATERIALS AND METHODS: One hundred MRI
      examinations performed with the intravenous injection of Gd-EOB-DTPA in patients
      with cirrhosis were reviewed retrospectively. Nodules were classified as HCC (n =
      70), indeterminate (n = 33), or benign (n = 22). Five readers independently
      reviewed each examination with and without hepatobiliary phase images (HBP).
      Lesion conspicuity scores were compared between the two readings. Lesion
      detection, confidence scores, and receiver operating characteristic (ROC)
      analysis were compared. RESULTS: Lesion detection was slightly improved for all
      lesion types with the inclusion of the HBP, and was substantially higher for
      small HCCs (96.0% versus 85.3%). Mean confidence scores for the diagnosis of HCC
      increased for HCCs overall and each size category (P < 0.001). Diagnostic
      performance improved with the addition of the HBP (aggregate AROC 87.7% versus
      80.0%, P < 0.01), and sensitivity for characterization improved (90.9% versus
      78.3%, P < 0.01) while specificity was unchanged. CONCLUSION: Hepatobiliary phase
      imaging may improve small lesion detection (<1 cm) and characterization of
      lesions in general, in MRI of the cirrhotic liver with Gd-EOB-DTPA.

PMID- 23011875
TI  - Should less motion sensitive T2-weighted BLADE TSE replace Cartesian TSE for
      female pelvic MRI?
AB  - OBJECTIVES: To prospectively compare the diagnostic performance of a non
      Cartesian k-space sampling T2-weighted TSE BLADE sequence with a conventional T2
      weighted TSE sequence in female pelvic organs. METHODS: Forty-seven patients with
      sonographically indeterminate adnexal masses or uterine lesions underwent
      sagittal BLADE and conventional TSE at 1.5 T after glucagon administration. Two
      radiologists independently determined their preferred sequence by rating: overall
      image diagnostic quality, conspicuity of the zonal anatomy and delineation of
      pathologies of the uterus and cervix, presence of artefacts, and of fluid in the
      pouch of Douglas (Wilcoxon signed rank test). Signal-to noise ratios (SNRs) and
      contrast-to-noise ratios (CNRs) were measured for the myometrium versus the
      rectus abdominis muscle (Student's t-test). RESULTS: BLADE significantly (p <
      0.0001) reduced motion and ghosting artefacts and showed improved conspicuity (p
      = 0.3/0.24), but overall image quality did not differ significantly (inter
      observer agreement BLADE kappa = 0.89; TSE kappa = 0.84). In the majority of
      cases (53.2 % vs 59.6 %, respectively, kappa = 0.82) radiologists preferred
      conventional TSE due to better image contrast (p < 0.0001) and visibility of free
      pelvic fluid (p <= 0.0001). SNR (TSE 57.5 +/- 37.7; BLADE 16.6 +/- 12.2) and CNR
      (TSE 40.4 +/- 33.5; BLADE 7.2 +/- 8.8) were significantly higher on conventional
      TSE (p < 0.0001). CONCLUSIONS: Although BLADE reduces motion artefacts and
      provides a clearer delineation of uterine zonal anatomy compared with
      conventional TSE, this comes at the expense of overall contrast. MAIN MESSAGES: *
      Use of BLADE may reduce T2 contrast and thus visibility of free pelvic fluid or
      cystic structures * Non-Cartesian sampling of k-space such as BLADE is beneficial
      due to less motion sensitivity * BLADE provides clearer delineation and
      conspicuity of uterine zonal anatomy on pelvic MRIs.

PMID- 23011876
TI  - Influence of pressure on the low-frequency vibrational modes of lysozyme and
      water: a complementary inelastic neutron scattering and molecular dynamics
      simulation study.
AB  - We performed complementary inelastic neutron scattering (INS) experiments and
      molecular dynamics (MD) simulations to study the influence of pressure on the low
      frequency vibrational modes of lysozyme in aqueous solution in the 1 atm-6 kbar
      range. Increasing pressure induces a high-frequency shift of the low-frequency
      part (<10 meV = 80 cm(-1)) of the vibrational density of states (VDOS), g(omega),
      of both lysozyme and water that reveals a stiffening of the interactions ascribed
      to the reduction of the protein and water volumes. Accordingly, high pressures
      increase the curvature of the free energy profiles of the protein quasiharmonic
      vibrational modes. Furthermore, the nonlinear influence of pressure on the
      g(omega) of lysozyme indicates a change of protein dynamics that reflects the
      nonlinear pressure dependence of the protein compressibility. An analogous
      dynamical change is observed for water and stems from the distortion of its
      tetrahedral structure under pressure. Moreover, our study reveals that the
      structural, dynamical, and vibrational properties of the hydration water of
      lysozyme are less sensitive to pressure than those of bulk water, thereby
      evidencing the strong influence of the protein surface on hydration water.

PMID- 23011877
TI  - Backbone 1H, 13C and 15N resonance assignments of the alpha-helical membrane
      protein TM0026 from Thermotoga maritima.
AB  - Critical to the use of solution NMR to describe the structure and flexibility of
      membrane proteins is the thorough understanding of the degree of perturbation
      induced by the detergent or other membrane mimetic. To develop a deeper
      understanding of the interaction between membrane proteins and micelles or
      bicelles, we will investigate the differences in structure and flexibility of a
      model membrane protein TM0026 from Thermotoga maritima using solution NMR. A
      comparison of the structural differences between TM0026 solubilized in different
      detergent combinations will provide important insight into the degree of
      modulation of membrane proteins by detergent physical properties. Here we report
      the nearly complete backbone and Cbeta resonance assignments of the two
      transmembrane helical model protein TM0026. These assignments are the first step
      to using TM0026 to elucidate the interaction between membrane proteins and
      membrane mimetics. 

PMID- 23011884
TI  - Functional effect of polymorphisms in 15q25 locus on CHRNA5 mRNA, bulky DNA
      adducts and TP53 mutations.
AB  - Genome-wide association studies have demonstrated that genetic polymorphisms
      influence the risk of developing lung cancer. Nicotinic acetylcholine receptor
      alpha3, alpha5 and beta4 genes (CHRNA3, CHRNA5 and CHRNB4) cluster at the 15q25.1
      lung cancer susceptibility locus. We genotyped 310 patients with non-small cell
      lung cancer and a control group of 348 cancer-free individuals for seven sequence
      variants located in CHRNA3 and CHRNA5 genes. Two of the polymorphisms (rs3829787
      and rs3841324) statistically influenced the risk of developing lung cancer. We
      found that four of the variants (rs3829787, rs3841324, rs588765 and rs3743073)
      were associated with differential levels of genetic alterations measured as the
      levels of hydrophobic DNA adducts in the adjacent histologically normal tissue of
      the lung cancer patients and as TP53 mutations in their lung tumors. The seven
      sequence variants formed three haplotypes with a frequency above 5%. The two most
      frequent haplotypes were associated with the risk of developing lung cancer and
      with smoking-related DNA alterations. We also found an association between CHRNA5
      mRNA levels and the sequence variants or haplotypes. In conclusion, our results
      showed that several of the polymorphisms and their haplotypes in CHRNA5/CHRNA3
      genes may have functional effects on (i) CHRNA5 mRNA levels, (ii) polycyclic
      aromatic hydrocarbon-DNA adduct levels, (iii) TP53 mutations and (iv)
      susceptibility to lung cancer.

PMID- 23011885
TI  - PbS-organic mesocrystals: the relationship between nanocrystal orientation and
      superlattice array.

PMID- 23011886
TI  - LacZ beta-galactosidase: structure and function of an enzyme of historical and
      molecular biological importance.
AB  - This review provides an overview of the structure, function, and catalytic
      mechanism of lacZ beta-galactosidase. The protein played a central role in Jacob
      and Monod's development of the operon model for the regulation of gene
      expression. Determination of the crystal structure made it possible to understand
      why deletion of certain residues toward the amino-terminus not only caused the
      full enzyme tetramer to dissociate into dimers but also abolished activity. It
      was also possible to rationalize alpha-complementation, in which addition to the
      inactive dimers of peptides containing the "missing" N-terminal residues restored
      catalytic activity. The enzyme is well known to signal its presence by
      hydrolyzing X-gal to produce a blue product. That this reaction takes place in
      crystals of the protein confirms that the X-ray structure represents an active
      conformation. Individual tetramers of beta-galactosidase have been measured to
      catalyze 38,500 +/- 900 reactions per minute. Extensive kinetic, biochemical,
      mutagenic, and crystallographic analyses have made it possible to develop a
      presumed mechanism of action. Substrate initially binds near the top of the
      active site but then moves deeper for reaction. The first catalytic step (called
      galactosylation) is a nucleophilic displacement by Glu537 to form a covalent bond
      with galactose. This is initiated by proton donation by Glu461. The second
      displacement (degalactosylation) by water or an acceptor is initiated by proton
      abstraction by Glu461. Both of these displacements occur via planar oxocarbenium
      ion-like transition states. The acceptor reaction with glucose is important for
      the formation of allolactose, the natural inducer of the lac operon.

PMID- 23011887
TI  - Ubiquitin-based probes prepared by total synthesis to profile the activity of
      deubiquitinating enzymes.
AB  - Epitope-tagged active-site-directed probes are widely used to visualize the
      activity of deubiquitinases (DUBs) in cell extracts, to investigate the
      specificity and potency of small-molecule DUB inhibitors, and to isolate and
      identify DUBs by mass spectrometry. With DUBs arising as novel potential drug
      targets, probes are required that can be produced in sufficient amounts and to
      meet the specific needs of a given experiment. The established method for the
      generation of DUB probes makes use of labor-intensive intein-based methods that
      have inherent limitations concerning the incorporation of unnatural amino acids
      and the amount of material that can be obtained. Here, we describe the total
      chemical synthesis of active-site-directed probes and their application to
      activity-based profiling and identification of functional DUBs. This synthetic
      methodology allowed the easy incorporation of desired tags for specific
      applications, for example, fluorescent reporters, handles for immunoprecipitation
      or affinity pull-down, and cleavable linkers. Additionally, the synthetic method
      can be scaled up to provide significant amounts of probe. Fluorescent ubiquitin
      probes allowed faster, in-gel detection of active DUBs, as compared to
      (immuno)blotting procedures. A biotinylated probe holding a photocleavable linker
      enabled the affinity pull-down and subsequent mild, photorelease of DUBs. Also,
      DUB activity levels were monitored in response to overexpression or knockdown,
      and to inhibition by small molecules. Furthermore, fluorescent probes revealed
      differential DUB activity profiles in a panel of lung and prostate cancer cells.

PMID- 23011888
TI  - Functional MRI of the thoracic spinal cord during vibration sensation.
AB  - PURPOSE: To demonstrate that it is possible to acquire accurate functional
      magnetic resonance images from thoracic spinal cord neurons. MATERIALS AND
      METHODS: The lower thoracic spinal dermatomes (T7-T11) on the right side of the
      body were mechanically stimulated by vibration for 15 participants. Neuronal
      responses to vibration sensation were measured in the thoracic spinal cord using
      a HASTE sequence on a 3 Tesla MRI system. RESULTS: Signal increases were observed
      in the corresponding lower thoracic spinal cord segments ipsilateral to the side
      of stimulation in the dorsal aspect of the spinal cord. CONCLUSION: This is the
      first study to provide proof of principle that functional imaging of the entire
      thoracic spinal cord is possible, by detecting neuronal activity in the thoracic
      spinal cord during sensory stimulation using spinal fMRI.

PMID- 23011890
TI  - CD146 expression and its close relationship to tumor progression in systemic
      malignancies besides gall bladder carcinomas.
AB  - Recent data suggest that CD146 may be involved in tumor development and may
      influence tumor prognosis in a number of systemic tumors besides gall bladder
      carcinomas. For instance, CD146 augments the development and progression of
      gastric carcinomas. It performs this function by accentuating epithelial
      mesenchymal transition (Liu et al., Int J Mol Sci 13:6399-6406, 2012). CD146 thus
      points towards a poor clinical outcome in gastric malignancies. An increase in
      gastric tissue vimentin is seen with an increase in CD146 levels. Similarly,
      around 8.7 % of lung adenocarcinomas express CD146. A decreased 5-year overall
      survival rate is seen following lung resection of pulmonary adenocarcinomas in
      male patients who express CD146 (Zeng et al., Proc Natl Acad Sci USA 109:1127
      1132; 2012).

PMID- 23011889
TI  - Synergistic induction of apoptosis and chemosensitization of human colorectal
      cancer cells by histone deacetylase inhibitor, scriptaid, and proteasome
      inhibitors: potential mechanisms of action.
AB  - Histone deacetylase inhibitors (HDACIs) exhibit modest results as single agents
      in preclinical and clinical studies against solid tumors; they often fall short
      and activate nuclear factor kappa-B (NFkappaB). Co-administration of HDACI with
      proteasome inhibitors (PIs), which interrupt NFkappaB pathways, may enhance HDACI
      lethality. The goal of this study was to determine whether PIs could potentiate
      HDACI, scriptaid (SCP)-mediated lethality, to unravel the associated mechanisms
      and to assess the effects of the combined inhibition of HDAC and proteasome on
      chemotherapy response in human colorectal cancer cells. Cancer cells were exposed
      to agents alone or in combination; cell growth inhibition was determined by MTT
      and colony formation assays. HDAC-, proteasome-, NFkappaB-activities, and
      reactive oxygen species (ROS) were quantified. Induction of apoptosis and cell
      cycle alterations were monitored by flow cytometry. Expression of cell
      cycle/apoptosis and cytoprotective/stress-related genes was determined by real
      time qRT-PCR and EIA, respectively. Potentiation of cancer cell sensitivity to
      chemotherapies by SCP/PIs was also evaluated. SCP and PIs: MG132, PI-1, or
      epoxomicin interact synergistically to potently inhibit cancer cell growth, alter
      cell cycle, induce apoptosis, reduce NFkappaB activity, and increase ROS
      generation. These events are associated with multiple perturbations in the
      expression of cell cycle, apoptosis, cytoprotective, and stress-related genes. Co
      administration of SCP and PIs strikingly increases the chemosensitivity of cancer
      cells (122-2 * 10(5)-fold) in a drug and SCP/PIs-dependent manner. This
      combination regimen markedly reduced the doses of chemotherapies with potent
      anticancer effects and less toxicity. A strategy combining HDAC/proteasome
      inhibition with chemotherapies warrants further investigation in colorectal
      cancer.

PMID- 23011891
TI  - Computational protein design suggests that human PCNA-partner interactions are
      not optimized for affinity.
AB  - Increasing the affinity of binding proteins is invaluable for basic and applied
      biological research. Currently, directed protein evolution experiments are the
      main approach for generating such proteins through the construction and screening
      of large mutant libraries. Proliferating cell nuclear antigen (PCNA) is an
      essential hub protein that interacts with many different partners to tightly
      regulate DNA replication and repair in all eukaryotes. Here, we used
      computational design to generate human PCNA mutants with enhanced affinity for
      several different partners. We identified double mutations in PCNA, outside the
      main partner binding site, that were predicted to increase PCNA-partner binding
      affinities compared to the wild-type protein by forming additional hydrophobic
      interactions with conserved residues in the PCNA partners. Affinity increases
      were experimentally validated with four different PCNA partners, demonstrating
      that computational design can reveal unexpected regions where affinity
      enhancements in natural systems are possible. The designed PCNA mutants can be
      used as a valuable tool for further examination of the regulation of PCNA-partner
      interactions during DNA replication and repair both in vitro and in vivo. More
      broadly, the ability to engineer affinity increases toward several PCNA partners
      suggests that interaction affinity is not an evolutionarily optimized trait of
      this system.

PMID- 23011892
TI  - Reactive tonsillar enlargement showing strong 18F-FDG uptake during the follow-up
      of follicular lymphoma.
AB  - The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG
      PET/CT) has become a standard procedure for the diagnosis, staging, and restaging
      in lymphoma patients. However, a relative high rate of false-positive results has
      been reported. We report a case of a 40-year-old man with a previous history of a
      nodal follicular lymphoma, stage IVA, treated with R-CHOP, which showed strong
      18F-FDG uptake in the Waldeyer's tonsillar ring during his follow-up, being
      considered highly suspicious of relapsed lymphoma. A surgical removal of the
      palatine tonsils and adenoids was performed, which showed reactive follicular
      hyperplasia. Furthermore, bone marrow biopsy revealed absence of neoplasia. The
      patient is still in follow-up with no signs of recurrent lymphoma. This case
      illustrates that, despite the high sensitivity for the detection of recurrent
      lymphoma, 18F-FDG uptake should be interpreted with great caution and
      confirmatory studies should be performed before any therapy.

PMID- 23011893
TI  - Elderly patients with colon cancer have unique tumor characteristics and poor
      survival.
AB  - BACKGROUND: The incidence of colon cancer increases with age, and colon cancer
      predominantly affects individuals >65 years old. However, there are limited data
      regarding clinical and pathologic factors, treatment characteristics, and
      survival of older patients with colon cancer. The objective of this study was to
      determine the effects of increasing age on colon cancer. METHODS: Patients
      diagnosed with colon cancer between 1988 and 2006 were identified through the Los
      Angeles County Cancer Surveillance Program, in Southern California. Patients were
      stratified into 4 age groups: 18-49, 50-64, 65-79, and >=80 years. Clinical and
      pathologic characteristics and disease-specific and overall survival were
      compared between patients from different age groups. RESULTS: A total of 32,819
      patients were assessed. Patients aged 18 to 49 and 65 to 79 years represented the
      smallest and largest groups, respectively. A near equal number of males and
      females were diagnosed with colon cancer in the 3 youngest age groups, whereas
      patients who were >=80 years old were more commonly white and female. Tumor
      location was different between groups, and the frequency of larger tumors (>5 cm)
      was greatest in youngest patients (18-49 years). The oldest patients (>=80 years)
      were administered chemotherapy at the lowest frequency, and disease-specific and
      overall survival rates decreased with increasing age. CONCLUSIONS: This
      investigation demonstrates that older age is associated with alterations in
      clinical and pathologic characteristics and decreased survival. This suggests
      that the phenotype of colon cancer and the efficacy of colon cancer therapies may
      be dependent on the age of patients.

PMID- 23011894
TI  - Stem cell transplantation as a therapy for cardiac fibrosis.
AB  - Cardiac fibrosis is a fundamental constituent of most cardiac pathologies and
      represents the upshot of nearly all types of cardiac injury. Generally, fibrosis
      is a scarring process, characterized by accumulation of fibroblasts and
      deposition of increasing amounts of extracellular matrix (ECM) proteins in the
      myocardium. Therapeutic approaches that control fibroblast activity and evade
      maladaptive processes could represent a potential strategy to attenuate
      progression towards heart failure. Currently, cell therapy is actively perceived
      as an alternative to traditional pharmacological management of myocardial
      infarction (MI). The majority of the studies applying stem cell therapy following
      MI have demonstrated a decline in fibrosis. However, it was not clearly
      recognized whether the decline in cardiac fibrosis was due to replacement of dead
      cardiomyocytes or because of the direct effects of paracrine factors released
      from the transplanted stem cells on the ECM. Therefore, the main focus of this
      review is to discuss the impact of different types of stem cells on cardiac
      fibrosis and associated cardiac remodelling in a variety of experimental models
      of heart failure, particularly MI.

PMID- 23011895
TI  - Assembly of prototype foamy virus strand transfer complexes on product DNA
      bypassing catalysis of integration.
AB  - Integrase is the key enzyme that mediates integration of retroviral DNA into
      cellular DNA which is essential for viral replication. Inhibitors of HIV-1 that
      target integrase recognize the nucleoprotein complexes formed by integrase and
      viral DNA substrate (intasomes) rather than the free enzyme. Atomic resolution
      structures of HIV-1 intasomes are therefore required to understand the mechanisms
      of inhibition and drug resistance. To date, prototype foamy virus (PFV) is the
      only retrovirus for which such structures have been determined. We show that PFV
      strand transfer complexes (STC) can be assembled on product DNA without going
      through the normal forward reaction pathway. The finding that a retroviral STC
      can be assembled in this way may provide a powerful tool to alleviate the
      obstacles that impede structural studies of nucleoprotein intermediates in HIV-1
      DNA integration.

PMID- 23011896
TI  - Sequencing the sixth base (5-hydroxymethylcytosine): selective DNA oxidation
      enables base-pair resolution.

PMID- 23011897
TI  - A matter of order: how E-selectin makes sweet contacts.
AB  - An entropy exclusive: Sialyl Lewis(x)  can be thought of as a "preorganized water
      oligomer". Recent research in the Ernst laboratory shows that the recognition of
      sialyl Lewis(x)  by E-selectin is exclusively entropy driven. This finding has
      implications for the design of carbohydrate-based drugs in general.

PMID- 23011898
TI  - Reproducibility of rapid short echo time CSI at 3 tesla for clinical
      applications.
AB  - PURPOSE: To validate the reproducibility of a chemical shift imaging (CSI)
      acquisition protocol with parallel imaging, using automated repositioning
      software. MATERIALS AND METHODS: Ten volunteers were imaged three times on two
      different 3 Tesla (T) MRI scanners, receiving anatomical imaging and two
      identical CSI measurements, using automated repositioning software for consistent
      repositioning of the CSI grid. Offcenter parameters of the CSI plane were
      analyzed. Coefficients of variation (CoV), Cramer-Rao lower bounds (CRLB),
      intraclass correlation coefficients (ICC), and coefficients of repeatability
      (CoR) for immediate repetition and between scanners were calculated for N
      acetylaspartate, total choline, creatine, myo-inositol (Myo) and
      glutamine+glutamate (Glx). Proportions of variance reflecting the effect of voxel
      location, volunteer, repetition, time instance and scanner were calculated from
      an analysis of variance analysis. RESULTS: The offcenter vector and angulations
      of the CSI grid differed less than 1 mm and 2 degrees  between all measurements.
      The mean CoV and CRLB were less than 30% for all metabolites, except for Myo. The
      variance due to voxel location in the volume of interest and the error represent
      the largest contributions in variability. The ICC is the lowest for Myo and Glx.
      CoR for immediate repetition and between scanners display values between 22 and
      83%. CONCLUSION: We propose a CSI protocol with acceptable reproducibility,
      applicable in clinical routine.

PMID- 23011899
TI  - Simulation of the mutation F76del on the von Hippel-Lindau tumor suppressor
      protein: mechanism of the disease and implications for drug development.
AB  - The von Hippel-Lindau tumor suppressor protein (pVHL) plays a central role in the
      oxygen-sensing pathway by regulating the degradation of the hypoxia-inducible
      factor (HIF-1alpha). The capture of HIF-1alpha by pVHL is regulated by an oxygen
      dependent hydroxylation of a specific conserved prolyl residue. The VHL gene is
      mutated in the von Hippel-Lindau cancer predisposition syndrome, which is
      characterized by the development of highly vascularized tumors and is associated
      with constitutively high levels of HIF-1alpha. The disturbance of the dynamic
      coupling between HIF-1alpha and pVHL bearing the commonly found mutation F76del
      was experimentally confirmed but the mechanism of such complex disruption is
      still not clear. Performing unbiased molecular dynamics simulations, we show that
      the F76del mutation may enlarge the HIF binding pocket in pVHL and induce the
      formation of an internal cavity in the hydrophobic core of the beta-domain, which
      can lead to a partial destabilization of the beta-sheets S1, S4, and S7 and a
      consequent loss of hydrogen bonds with a conserved recognition motif in HIF. The
      newly formed cavity has a significant druggability score and may be a suitable
      target for stabilizing ligands. Studies of this nature may help to fill the
      information gap between genotype-phenotype correlations with details obtained at
      atomic level and provide basis for future development of drug candidates, such as
      pharmacological chaperones, with the specific aim of reverting the dysfunction of
      such pathological protein complexes found in patients with VHL.

PMID- 23011900
TI  - Domain-specific and domain-general constraints on word and sequence learning.
AB  - The relative influences of language-related and memory-related constraints on the
      learning of novel words and sequences were examined by comparing individual
      differences in performance of children with and without specific deficits in
      either language or working memory. Children recalled lists of words in a Hebbian
      learning protocol in which occasional lists repeated, yielding improved recall
      over the course of the task on the repeated lists. The task involved presentation
      of pictures of common nouns followed immediately by equivalent presentations of
      the spoken names. The same participants also completed a paired-associate
      learning task involving word-picture and nonword-picture pairs. Hebbian learning
      was observed for all groups. Domain-general working memory constrained immediate
      recall, whereas language abilities impacted recall in the auditory modality only.
      In addition, working memory constrained paired-associate learning generally,
      whereas language abilities disproportionately impacted novel word learning.
      Overall, all of the learning tasks were highly correlated with domain-general
      working memory. The learning of nonwords was additionally related to general
      intelligence, phonological short-term memory, language abilities, and implicit
      learning. The results suggest that distinct associations between language- and
      memory-related mechanisms support learning of familiar and unfamiliar
      phonological forms and sequences.

PMID- 23011901
TI  - Contribution of myeloid cell subsets to liver fibrosis in parasite infection.
AB  - Accumulation of extracellular matrix components secreted by fibroblasts is a
      normal feature of wound healing during acute inflammation. However, during most
      chronic/persistent inflammatory diseases, this tissue repair mechanism is
      incorrectly regulated and results in irreversible fibrosis in various organs.
      Fibrosis that severely affects tissue architecture and can cause organ failure is
      a major cause of death in developed countries. Organ-recruited lymphoid (mainly T
      cells) and myeloid cells (eosinophils, basophils, macrophages and DCs) have long
      been recognized in their participation to the development of fibrosis. In
      particular, a central role for recruited monocyte-derived macrophages in this
      excessive connective tissue deposit is more and more appreciated. Moreover, the
      polarization of monocyte-derived macrophages in classically activated (IFNgamma
      dependent) M1 cells or alternatively activated (IL-4/IL-13) M2 cells, that
      mirrors the Th1/Th2 polarization of T cells, is also documented to contribute
      differentially to the fibrotic process. Here, we review the current understanding
      of how myeloid cell subpopulations affect the development of fibrosis in parasite
      infections.

PMID- 23011902
TI  - Predictors of newly diagnosed cancer patients' understanding of the goals of
      their care at initiation of chemotherapy.
AB  - BACKGROUND: The American Society of Clinical Oncology Quality Oncology Practice
      Initiative endorses in their core measures that providers should discuss the
      goals of care (GOC) at the time of chemotherapy consent. GOC refers to
      chemotherapy treatment intent: cure versus noncure. In this study, the authors
      sought to determine whether attributes of patients and initial patient-physician
      encounters were associated with patients' understanding of their GOC. METHODS: In
      total, the authors surveyed 125 consecutive, newly diagnosed patients who were
      receiving chemotherapy for solid malignancies at a single academic cancer center
      and performed a medical record review for additional data. Patient understanding
      of their oncologist's GOC and oncologist's reported GOC were compared. The
      primary outcome was concordance of patient-physician dyads regarding the GOC
      (cure vs noncure). RESULTS: One hundred twenty-five of 137 of eligible patients
      (91%) completed the survey. Only 95 of 125 patient-physician pairs (75%) patient
      physician pairs were concordant regarding the GOC. In a multivariable logistic
      regression, both older patients (odds ratio, 0.21; 95% confidence interval, 0.08
      0.57) and non-native English speakers had an almost 80% lower odds (odds ratio,
      0.23; 95% confidence interval, 0.05-0.93) of GOC concordance compared with
      younger patients and native English speakers. Patients who received printed
      chemotherapy information during the patient-physician consent process had almost
      3 times greater odds (odds ratio, 2.88; 95% confidence interval, 1.24-6.68) of
      GOC concordance with their physician compared with those who did not receive
      materials. CONCLUSIONS: Patient misunderstanding of GOC was substantial, with 25%
      of cancer patients misunderstanding the goal of their chemotherapy treatment. Key
      predictors of GOC misunderstanding included factors that potentially were
      amenable to interventions at the time of chemotherapy consent.

PMID- 23011903
TI  - Three-dimensional brain phantom containing bone and grey matter structures with a
      realistic head contour.
AB  - INTRODUCTION: A physical 3-dimensional phantom that simulates PET/SPECT images of
      static regional cerebral blood flow in grey matter with a realistic head contour
      has been developed. This study examined the feasibility of using this phantom for
      evaluating PET/SPECT images. METHODS: The phantom was constructed using a
      transparent, hydrophobic photo-curable polymer with a laser-modelling technique.
      The phantom was designed to contain the grey matter, the skull, and the trachea
      spaces filled with a radioactive solution, a bone-equivalent solution of
      K(2)HPO(4), and air, respectively. The grey matter and bone compartments were
      designed to establish the connectivity. A series of experiments was performed to
      confirm the accuracy and reproducibility of the phantom using X-ray CT, SPECT,
      and PET. RESULTS: The total weight was 1997 +/- 2 g excluding the inner liquid,
      and volumes were 563 +/- 1 and 306 +/- 2 mL, corresponding to the grey matter and
      bone compartments, respectively. The apparent attenuation coefficient averaged
      over the whole brain was 0.168 +/- 0.006 cm(-1) for Tc-99 m, which was consistent
      with the previously reported value for humans (0.168 +/- 0.010 cm(-1)). Air
      bubbles were well removed from both grey-matter and bone compartments, as
      confirmed by X-ray CT. The phantom was well adapted to experiments using PET and
      SPECT devices. CONCLUSION: The 3-dimensional brain phantom constructed in this
      study may be of use for evaluating the adequacy of SPECT/PET reconstruction
      software programs.

PMID- 23011904
TI  - NMR structure of the calflagin Tb24 flagellar calcium binding protein of
      Trypanosoma brucei.
AB  - Flagellar calcium binding proteins are expressed in a variety of trypanosomes and
      are potential drug targets for Chagas disease and African sleeping sickness. The
      flagellar calcium binding protein calflagin of Trypanosoma brucei (called Tb24)
      is a myristoylated and palmitoylated EF-hand protein that is targeted to the
      inner leaflet of the flagellar membrane. The Tb24 protein may also interact with
      proteins on the membrane surface that may be different from those bound to
      flagellar calcium binding proteins (FCaBPs) in T. cruzi. We report here the NMR
      structure of Tb24 that contains four EF-hand motifs bundled in a compact
      arrangement, similar to the overall fold of T. cruzi FCaBP (RMSD = 1.0 A). A
      cluster of basic residues (K22, K25, K31, R36, and R38) located on a surface near
      the N-terminal myristoyl group may be important for membrane binding. Non
      conserved residues on the surface of a hydrophobic groove formed by EF2 (P91,
      Q95, D103, and V108) and EF4 (C194, T198, K199, Q202, and V203) may serve as a
      target protein binding site and could have implications for membrane target
      recognition.

PMID- 23011905
TI  - N-(Diazoacetyl)oxazolidin-2-thiones as sulfur-donor reagents: asymmetric
      synthesis of thiiranes from aldehydes.

PMID- 23011906
TI  - Relativistic and non-relativistic electronic molecular-structure calculations for
      dimers of 4p-, 5p-, and 6p-block elements.
AB  - We report results of non-relativistic and two-component relativistic single
      reference coupled-cluster with single and double and perturbative triple
      excitations [CCSD(T)] treatments for the 4p-block dimers Ga(2) to Br(2) , the 5p
      block dimers In(2) to I(2) , and their atoms. Extended basis sets up to pentuple
      zeta are employed and energies extrapolated to the complete basis-set limit.
      Relativistic and non-relativistic results for the dissociation energy D(e) are in
      close agreement with each other and previously published data, provided non
      relativistic or scalar-relativistic results are corrected for spin-orbit
      contributions taken from the literature. An exception is Te(2) where theoretical
      results scatter by 0.085 eV. By virtue of this agreement it is unexpected that
      comparison with the experimental D(0) or D(e) dissociation energies (zero-point
      vibrational effects are negligible in this context) reveal errors larger than 0.1
      eV for Ga(2), Ge(2), and Sb(2). Only relativistic treatments are presented for
      the 6p-block cases Tl(2) to At(2). Sufficient agreement with experimental data is
      found only for Pb(2) and Bi(2), the deviation of the computed and experimental
      D(0) values for Po(2) is again larger than 0.1 eV. Deviations of 0.1 eV between
      the computed and experimental D(0) values are a major reason for concern and call
      for additional investigations in both fields to clarify the situation.

PMID- 23011907
TI  - Contrast-enhanced specific absorption rate-efficient 3D cardiac cine with
      respiratory-triggered radiofrequency gating.
AB  - PURPOSE: To investigate the use of radiofrequency (RF) gating in conjunction with
      a paramagnetic contrast agent to reduce the specific absorption rate (SAR) and
      increase the blood-myocardium contrast in balanced steady-state free precession
      (bSSFP) 3D cardiac cine. MATERIALS AND METHODS: RF gating was implemented by
      synchronizing the RF-excitation with an external respiratory sensor (bellows),
      which could additionally be used for respiratory gating. For reference,
      respiratory-gated 3D cine images were acquired without RF gating. Free-breathing
      3D cine images were acquired in eight healthy subjects before and after contrast
      injection (Gd-BOPTA) and compared to breath-hold 2D cine. RESULTS: RF-gated 3D
      cine reduced the SAR by nearly 40% without introducing significant artifacts
      while providing left ventricle (LV) measurements similar to those obtained with
      2D cine. The contrast-to-noise ratio (CNR) was significantly higher for 3D cine
      compared to 2D cine, both before and after contrast injection; however, no
      statistically significant CNR increase was observed for the postcontrast 3D cine
      compared to the precontrast acquisitions. CONCLUSION: Respiratory-triggered RF
      gating significantly reduces SAR in 3D cine acquisitions, which may enable a more
      widespread clinical use of 3D cine. Furthermore, CNR of 3D bSSFP cine is higher
      than of 2D and administration of Gd-BOPTA does not improve the CNR of 3D cine.

PMID- 23011908
TI  - Summary of in vitro genetic toxicology assay results: expected and unexpected
      effects of recent study design modifications.
AB  - Key modifications to in vitro genetic toxicology testing have been made in the
      last 5 years including the use of optimization approaches such as structure
      activity relationships and screening assays to identify and eliminate potentially
      genotoxic chemicals from further consideration, better guidance on cytotoxicity
      assessment and dose selection, and greater use of p53-competent human cells. To
      determine the effect of these changes on testing outcomes, the pattern of
      positive results across assays conducted by BioReliance from 2005 to 2010 was
      examined. Data were tabulated for good laboratory practice (GLP)-compliant Ames,
      mouse lymphoma (MLA), chromosome aberration in Chinese hamster ovary (CHO) cells,
      and in human peripheral blood lymphocytes (HPBL) assays along with non-GLP
      screening Ames assays. A decrease in percentage of positive results in MLA and
      CHO chromosome aberration assays was observed, whereas the percentage of positive
      Ames assays remained consistent. This was not unexpected because MLA and CHO
      cytogenetic assays have undergone the most substantive changes (e.g., the
      establishment of the Global Evaluation Factor for the MLA and the use of the
      relative increase in cell counts in CHO chromosome aberration assays). Over the
      last 5 years, there has been an increase in the percentage of positive results
      observed in the chromosome aberration assay in HPBL. It is speculated that this
      may have led to an increase in HPBL-positive results if the chemicals routed to
      HPBL had previous positive genotoxicity results. Another factor may be the lack
      of a reliable cytotoxicity measurement in the HPBL assay.

PMID- 23011909
TI  - A critical eye: praise directed toward traits increases children's eye fixations
      on errors and decreases motivation.
AB  - Although there is evidence that praise of different types (i.e., generic vs.
      nongeneric) influences motivation, it is unclear how this occurs. Generic praise
      (e.g., "You are smart") conveys that a child possesses a trait responsible for
      their performance, whereas nongeneric praise (e.g., "You worked hard") conveys
      that performance is effort-based. Because praise conveys the basis for success,
      praise may change the interpretation and salience of errors. Specifically,
      generic praise may highlight the threatening nature of error (i.e., the child
      does not possess this trait). Because attention is drawn to threats in the
      environment, we expected generic praise to increase attention to error. We used
      eyetracking to measure implicit responses to errors (i.e., visual attention:
      fixation counts and durations) in order to determine the relation between visual
      attention and verbal reports of motivation (persistence and self-evaluations) in
      30 four- to seven-year-old children. Children first saw pictures attributed to
      them, for which they received either generic or nongeneric praise. The children
      then saw pictures attributed to them that contained errors--that is, missing
      features. As a pretest and posttest, the children saw pictures that were "drawn
      by other children," half of which contained errors. The results indicated that
      children who received generic praise ("you are a good drawer") produced more and
      longer fixations on errors, both their "own" and on "other children's," than did
      children who received nongeneric praise ("you did a good job drawing"). More
      fixations on errors were related to lower persistence and lower self-evaluations.
      These results suggest that generic praise increases attention to errors because
      error threatens the possession of a positive trait.

PMID- 23011910
TI  - An index of prenatal steroid exposure predicts adult face perception skills.
AB  - Face perception skills are fundamental to social cognition, yet they vary
      markedly across individuals. This diversity has stimulated controversy over the
      relative contributions of genetic factors, prenatal environment, and postnatal
      experience to face perception. Recent twin studies have found that face
      perception is heritable, highlighting the potential for substantial prenatal
      determination of these skills. In contrast, previous work on potential influences
      of the prenatal hormonal environment on social cognition have found no
      association between 2D:4D, a marker for prenatal androgen exposure, and
      processing of facial emotional expressions, apparently precluding a major role
      for prenatal hormones in governing face perception. We propose that substantial
      predictive relationships between 2D:4D and face perception may have been masked
      in previous work because the task employed required both face perception and
      processing of others' emotions, the latter component being greatly influenced by
      circulating hormones in adults. To assess prenatal hormone influences on face
      perception without requiring emotion processing, we related 2D:4D to the face
      inversion effect (FIE), a measure of the recruitment of specialist face processes
      to visual perception. The magnitude of the resulting predictive relationship (r =
      .52) compared surprisingly well with that found between identical twins' face
      perception (rs = .27-.61), suggesting that mechanisms of 2D:4D may account for a
      substantial proportion of perinatal influences on face processing. Furthermore,
      we employed 2D:4D as a common scale to map individual differences in the FIE onto
      prenatal testosterone:estrogen ratios, assayed by Lutchmaya, Baron-Cohen,
      Raggatt, Knickmeyer, and Manning (Early Human Development 77:23-28, 2004). The
      substantial overlap between the two data sets further implicates prenatal
      steroids in adult face perception skills.

PMID- 23011911
TI  - Prognostic factors for recurrence and survival in anal cancer: generating
      hypotheses from the mature outcomes of the first United Kingdom Coordinating
      Committee on Cancer Research Anal Cancer Trial (ACT I).
AB  - BACKGROUND: Only 2 prospective studies have previously reported prognostic
      factors for anal cancer, European Organization for Research and Treatment of
      Cancer trial 22861 (EORTC 22861) and Radiation Therapy Oncology Group trial 98-11
      (RTOG 98-11). Both of those trials reported that clinically positive lymph nodes
      and male sex predicted poorer overall survival (OS). The EORTC 22861 trial
      indicated that the same factors were prognostic for locoregional control. In the
      current report, the authors investigated potential prognostic factors from the
      first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial
      (ACT I), in which patients were randomized to receive either radiotherapy alone
      or chemoradiation (CRT) with concurrent 5-fluorouracil/mitomycin C. METHODS: In
      the ACT I trial, associations between several baseline characteristics and 3
      endpoints were investigated: locoregional failure (LRF), anal cancer death (ACD),
      and OS. The analyses were restricted to 292 patients who received CRT, which
      subsequently became standard treatment. A score was derived using multivariable
      Cox regression to identify the set of factors that, together, had the best
      prognostic performance. This score was then validated with a large, independent
      prospective trial (the ACT II trial). RESULTS: Palpable, clinically positive
      lymph nodes were associated with LRF (P = .012), a greater risk of ACD (P =
      .031), and decreased OS (P = .006) in multivariable analyses. Men had worse
      outcomes than women for LRF (P = .036), ACD (P = .039), and OS (P = .008). On
      average, a lower hemoglobin level had an adverse effect on ACD (P = .008), and a
      higher white blood cell count had an adverse effect on OS (P = .001). However,
      external validation of the score was poor for LRF (area under the curve [AUC] =
      54%) but was better for ACD (AUC = 67%) and OS (AUC = 63%). CONCLUSIONS: The
      results from this analysis of the ACT I trial supported evidence for palpable
      lymph nodes and male sex as prognostic factors for LRF and OS, and lower
      hemoglobin levels and a higher white blood cell count were identified as
      prognostic factors for ACD and OS, respectively.

PMID- 23011912
TI  - Oxidative stress and myocardial injury in the diabetic heart.
AB  - Reactive oxygen or nitrogen species play an integral role in both myocardial
      injury and repair. This dichotomy is differentiated at the level of species type,
      amount and duration of free radical generated. Homeostatic mechanisms designed to
      prevent free radical generation in the first instance, scavenge, or enzymatically
      convert them to less toxic forms and water, playing crucial roles in the
      maintenance of cellular structure and function. The outcome between functional
      recovery and dysfunction is dependent upon the inherent ability of these
      homeostatic antioxidant defences to withstand acute free radical generation, in
      the order of seconds to minutes. Alternatively, pre-existent antioxidant capacity
      (from intracellular and extracellular sources) may regulate the degree of free
      radical generation. This converts reactive oxygen and nitrogen species to the
      role of second messenger involved in cell signalling. The adaptive capacity of
      the cell is altered by the balance between death or survival signal converging at
      the level of the mitochondria, with distinct pathophysiological consequences that
      extends the period of injury from hours to days and weeks. Hyperglycaemia,
      hyperlipidaemia and insulin resistance enhance oxidative stress in the diabetic
      myocardium that cannot adapt to ischaemia-reperfusion. Altered glucose flux,
      mitochondrial derangements and nitric oxide synthase uncoupling in the presence
      of decreased antioxidant defence and impaired prosurvival cell signalling may
      render the diabetic myocardium more vulnerable to injury, remodelling and heart
      failure.

PMID- 23011913
TI  - Aesthetic amenities and safety hazards associated with walking and bicycling for
      transportation in New York City.
AB  - BACKGROUND: One strategy to address health problems related to insufficient
      physical activity is to examine modifiable neighborhood characteristics
      associated with active transportation. PURPOSE: The aim of this study is to
      evaluate whether neighborhoods with more aesthetic amenities (sidewalk cafes,
      street trees, and clean sidewalks) and fewer safety hazards (pedestrian-auto
      fatalities and homicides) are associated with active transportation. METHODS: The
      2003 Community Health Survey in New York City, which asked about active
      transportation (walking or bicycling >10 blocks) in the past 30 days, was linked
      to ZIP-code population census and built environment characteristics. Adjusted
      associations were estimated for dichotomous (any active transportation versus
      none) and continuous (trip frequency) active transportation outcomes. RESULTS:
      Among 8,034 adults, those living near sidewalk cafes were 10 % more likely to
      report active transportation (p = 0.01). Homicide rate was associated with less
      frequent active transportation among those reporting any active transportation (p
      = 0.002). CONCLUSIONS: Investments in aesthetic amenities or homicide prevention
      may help to promote active transportation.

PMID- 23011914
TI  - Locations of joint physical activity in parent-child pairs based on accelerometer
      and GPS monitoring.
AB  - BACKGROUND: Parental factors may play an important role in influencing children's
      physical activity levels. PURPOSE: This cross-sectional study sought to describe
      the locations of joint physical activity among parents and children. METHODS:
      Parent-child pairs (N = 291) wore an Actigraph GT2M accelerometer and GlobalSat
      BT-335 global positioning systems (GPS) device over the same 7-day period.
      Children were ages 8-14 years. Joint behavior was defined by a linear separation
      distance of less than 50 m between parent and child. Land use classifications
      were assigned to GPS datapoints. RESULTS: Joint physical activity was spread
      across residential locations (35 %), and commercial venues (24 %), and open
      spaces/parks (20 %). Obese children and parents performed less joint physical
      activity in open spaces/parks than under/normal weight children and parents (ps <
      0.01). CONCLUSIONS: Understanding where joint parent-child physical activity
      naturally occurs may inform location-based interventions to promote these
      behaviors.

PMID- 23011915
TI  - An efficient route to polysubstituted tetrahydronaphthols: silver-catalyzed [4+2]
      cyclization of 2-alkylbenzaldehydes and alkenes.

PMID- 23011916
TI  - Single-breath xenon polarization transfer contrast (SB-XTC): implementation and
      initial results in healthy humans.
AB  - PURPOSE: To implement and characterize a single-breath xenon transfer contrast
      (SB-XTC) method to assess the fractional diffusive gas transport F in the lung:
      to study the dependence of F and its uniformity as a function of lung volume; to
      estimate local alveolar surface area per unit gas volume S(A)/V(Gas) from
      multiple diffusion time measurements of F; to evaluate the reproducibility of the
      measurements and the necessity of B(1) correction in cases of centric and
      sequential encoding. MATERIALS AND METHODS: In SB-XTC three or four gradient echo
      images separated by inversion/saturation pulses were collected during a breath
      hold in eight healthy volunteers, allowing the mapping of F (thus S(A)/V(Gas))
      and correction for other contributions such as T(1) relaxation, RF depletion and
      B(1) inhomogeneity from inherently registered data. RESULTS: Regional values of F
      and its distribution were obtained; both the mean value and heterogeneity of F
      increased with the decrease of lung volume. Higher values of F in the bases of
      the lungs in supine position were observed at lower volumes in all volunteers.
      Local S(A)/V(Gas) (with a mean +/- standard deviation of S(A)/V(Gas) = 89 +/- 30
      cm(-1)) was estimated in vivo near functional residual capacity. Calibration of
      SB-XTC on phantoms highlighted the necessity for B(1) corrections when k-space is
      traversed sequentially; with centric ordering B(1) distribution correction is
      dispensable. CONCLUSION: The SB-XTC technique is implemented and validated for in
      vivo measurements of local S(A)/V(Gas).

PMID- 23011917
TI  - Initiated chemical vapor deposition-based method for patterning polymer and metal
      microstructures on curved substrates.
AB  - A simple, efficient, and scalable method for patterning microstructures on curved
      substrates is demonstrated. Initiated chemical vapor deposition is used to
      synthesize a thin film that crosslinks upon UV exposure. Polymeric features are
      defined on glass rods with high curvature and used as masks for metal patterning.
      Additionally, vapor-deposited polymer layers are selectively patterned to produce
      bifunctional surfaces.

PMID- 23011918
TI  - Increased expression of the glucose-responsive gene, RCAN1, causes
      hypoinsulinemia, beta-cell dysfunction, and diabetes.
AB  - RCAN1 is a chromosome 21 gene that controls secretion in endocrine cells,
      regulates mitochondrial function, and is sensitive to oxidative stress. Regulator
      of calcineurin 1 (RCAN1) is also an endogenous inhibitor of the protein
      phosphatase calcineurin, the inhibition of which leads to hypoinsulinemia and
      diabetes in humans and mice. However, the presence or the role of RCAN1 in
      insulin-secreting beta-cells and its potential role in the pathogenesis of
      diabetes is unknown. Hence, the aim of this study is to investigate the presence
      of RCAN1 in beta-cells and identify its role in beta-cell function. RCAN1 is
      expressed in mouse islets and in the cytosol of pancreatic beta-cells. We find
      RCAN1 is a glucose-responsive gene with a 1.5-fold increase in expression
      observed in pancreatic islets in response to chronic hyperglycemia. The
      overexpression of the human RCAN1.1 isoform in mice under the regulation of its
      endogenous promoter causes diabetes, age-associated hyperglycemia, reduced
      glucose tolerance, hypoinsulinemia, loss of beta-cells, reduced beta-cell insulin
      secretion, aberrant mitochondrial reactive oxygen species production, and the
      down-regulation of key beta-cell genes. Our data therefore identifies a novel
      molecular link between the overexpression of RCAN1 and beta-cell dysfunction. The
      glucose-responsive nature of RCAN1 provides a potential mechanism of action
      associated with the beta-cell dysfunction observed in diabetes.

PMID- 23011919
TI  - Transient, inducible, placenta-specific gene expression in mice.
AB  - Molecular understanding of placental functions and pregnancy disorders is limited
      by the absence of methods for placenta-specific gene manipulation. Although
      persistent placenta-specific gene expression has been achieved by lentivirus
      based gene delivery methods, developmentally and physiologically important
      placental genes have highly stage-specific functions, requiring controllable,
      transient expression systems for functional analysis. Here, we describe an
      inducible, placenta-specific gene expression system that enables high-level,
      transient transgene expression and monitoring of gene expression by live
      bioluminescence imaging in mouse placenta at different stages of pregnancy. We
      used the third generation tetracycline-responsive tranactivator protein Tet-On
      3G, with 10- to 100-fold increased sensitivity to doxycycline (Dox) compared with
      previous versions, enabling unusually sensitive on-off control of gene expression
      in vivo. Transgenic mice expressing Tet-On 3G were created using a new integrase
      based, site-specific approach, yielding high-level transgene expression driven by
      a ubiquitous promoter. Blastocysts from these mice were transduced with the Tet
      On 3G-response element promoter-driving firefly luciferase using lentivirus
      mediated placenta-specific gene delivery and transferred into wild-type
      pseudopregnant recipients for placenta-specific, Dox-inducible gene expression.
      Systemic Dox administration at various time points during pregnancy led to
      transient, placenta-specific firefly luciferase expression as early as d 5 of
      pregnancy in a Dox dose-dependent manner. This system enables, for the first
      time, reliable pregnancy stage-specific induction of gene expression in the
      placenta and live monitoring of gene expression during pregnancy. It will be
      widely applicable to studies of both placental development and pregnancy, and the
      site-specific Tet-On G3 mouse will be valuable for studies in a broad range of
      tissues.

PMID- 23011920
TI  - Morphological evidence for enhanced kisspeptin and neurokinin B signaling in the
      infundibular nucleus of the aging man.
AB  - Peptidergic neurons synthesizing kisspeptin (KP) and neurokinin B (NKB) in the
      hypothalamic infundibular nucleus have been implicated in negative sex steroid
      feedback to GnRH neurons. In laboratory rodents, testosterone decreases KP and
      NKB expression in this region. In the present study, we addressed the hypothesis
      that the weakening of this inhibitory testosterone feedback in elderly men
      coincides with enhanced KP and NKB signaling in the infundibular nucleus. This
      central hypothesis was tested in a series of immunohistochemical studies on
      hypothalamic sections of male human individuals that were divided into arbitrary
      "young" (21-49 yr, n = 11) and "aged" (50-67 yr, n = 9) groups. Quantitative
      immunohistochemical experiments established that the regional densities of NKB
      immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts
      they formed onto GnRH neurons, exceeded several times those of the KP-IR
      elements. Robust aging-dependent enhancements were identified in the regional
      densities of KP-IR perikarya and fibers and the incidence of afferent contacts
      they established onto GnRH neurons. The abundance of NKB-IR perikarya, fibers,
      and axonal appositions to GnRH neurons also increased with age, albeit to lower
      extents. In dual-immunofluorescent studies, the incidence of KP-IR NKB perikarya
      increased from 36% in young to 68% in aged men. Collectively, these
      immunohistochemical data suggest an aging-related robust enhancement in central
      KP signaling and a moderate enhancement in central NKB signaling. These changes
      are compatible with a reduced testosterone negative feedback to KP and NKB
      neurons. The heavier KP and NKB inputs to GnRH neurons in aged, compared with
      young, men may play a role in the enhanced central stimulation of the
      reproductive axis. It requires clarification to what extent the enhanced KP and
      NKB signaling upstream from GnRH neurons is an adaptive response to hypogonadism
      or, alternatively, a consequence of a decline in the androgen sensitivity of KP
      and NKB neurons.

PMID- 23011921
TI  - Kiss of the mutant mouse: how genetically altered mice advanced our understanding
      of kisspeptin's role in reproductive physiology.
AB  - The kisspeptin system has emerged as one of the most important circuits within
      the central network governing reproduction. Although kisspeptin physiology has
      been examined in many species, much of our understanding of this system has come
      from mice. Recently, the study of several innovative strains of genetically
      engineered mouse models has revealed intriguing and unexpected insights into the
      functions of kisspeptin signaling in the hypothalamus. Here, we review the
      advancements in our knowledge of the central kisspeptin system through the use of
      mutant mice.

PMID- 23011923
TI  - Induction of IGFBP-1 expression by cAMP is associated with histone acetylation
      status of the promoter region in human endometrial stromal cells.
AB  - Many genes are up- or down-regulated in human endometrial stromal cells (ESCs)
      undergoing decidualization. IGF-binding protein-1 (IGFBP-1) and prolactin (PRL)
      are preferentially expressed during decidualization and are recognized as
      specific markers of decidualization. This study investigated the involvement of
      epigenetic mechanisms in the regulation of IGFBP-1 and PRL induction by
      decidualization in ESCs. ESCs isolated from the proliferative phase endometrium
      were incubated with cAMP to induce decidualization. Human dermal fibroblasts
      (HDFs) were used as a nonendometrial control. cAMP induced the expressions of
      both genes in ESCs but induced the expression of only PRL in HDFs. Histone
      acetylation levels of the IGFBP-1 promoter region evaluated by chromatin
      immunoprecipitation assay were higher in ESCs than in HDFs. The IGFBP-1 promoter
      regions in the two cell types showed similar levels of DNA hypomethylation. The
      histone acetylation levels and DNA methylation status of the PRL promoter and
      enhancer regions were similar in the two cell types. cAMP had no significant
      effects on the histone acetylation levels and DNA methylation status of the IGFBP
      1 promoter and the PRL promoter and enhancer regions in ESCs. Cotreatment of HDF
      with cAMP and histone deacetylase inhibitors induced IGFBP-1 expression, which
      was accompanied by an increased histone acetylation level and recruitment of
      CCAAT/enhancer-binding protein-beta to the promoter region. These results show
      that, during decidualization in ESCs, high histone acetylation status of the
      promoter regions of IGFBP-1 and PRL is associated with the induction of the IGFBP
      1 and PRL genes by making the promoter regions accessible to transcriptional
      factors.

PMID- 23011922
TI  - Central depletion of brain-derived neurotrophic factor in mice results in high
      bone mass and metabolic phenotype.
AB  - Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal
      differentiation/survival, the regulation of food intake, and the pathobiology of
      obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in
      osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether
      central BDNF affects bone mass in vivo is not known. We therefore examined bone
      mass and energy use in brain-targeted BDNF conditional knockout mice
      (Bdnf(2lox/2lox)/93). The deletion of BDNF in the brain led to a metabolic
      phenotype characterized by hyperphagia, obesity, and increased abdominal white
      adipose tissue. Central BDNF deletion produces a marked skeletal phenotype
      characterized by increased femur length, elevated whole bone mineral density, and
      bone mineral content. The skeletal changes are developmentally regulated and
      appear concurrently with the metabolic phenotype, suggesting that the metabolic
      and skeletal actions of BDNF are linked. The increased bone development is
      evident in both the cortical and trabecular regions. Compared with control,
      Bdnf(2lox/2lox)/93 mice show greater trabecular bone volume (+50% for distal
      femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical
      thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal
      and metabolic phenotypes were gender dependent, with female being more affected
      than male mice. However, uncoupling protein-1 expression in brown fat, a marker
      of sympathetic tone, was not different between genotypes. We show that deletion
      of central BDNF expression in mice results in increased bone mass and white
      adipose tissue, with no significant changes in sympathetic signaling or
      peripheral serotonin, associated with hyperphagia, obesity, and leptin
      resistance.

PMID- 23011924
TI  - Use of adjuvant trastuzumab in women with human epidermal growth factor receptor
      2 (HER2)-positive breast cancer by race/ethnicity and education within the
      National Comprehensive Cancer Network.
AB  - BACKGROUND: Trastuzumab for human epidermal growth factor receptor 2 (HER2)
      positive breast cancer is highly efficacious yet costly and time-intensive, and
      few data are available about its use. The authors of this report examined receipt
      and completion of adjuvant trastuzumab by race/ethnicity and education for women
      with HER2-positive disease. METHODS: The National Comprehensive Cancer Network
      Breast Cancer Outcomes Database was used to identify 1109 women who were
      diagnosed with stage I through III, HER2-positive breast cancer during September
      2005 through December 2008 and were followed for >=1 year. The authors used
      multivariable logistic regression to assess the association of race/ethnicity and
      education with the receipt of trastuzumab and, among those women who initiated
      trastuzumab, with the completion of > 270 days of therapy. RESULTS: The cohort
      was 75% white, 8% black, and 9% Hispanic; and 20% of women had attained a high
      school degree or less. Most women (83%) received trastuzumab, and no significant
      differences were observed according to race/ethnicity or socioeconomic status.
      Among the women who initiated trastuzumab, 73% of black women versus 87% of white
      women (P = .007) and 70% of women with less than a high school education versus
      90% of women with a college degree completed > 270 days of therapy (P = .006). In
      adjusted analyses, black women (vs white women) and women without a high school
      degree (vs those with a college degree) had lower odds of completing therapy
      (black women: odds ratio, 0.45; 95% confidence interval, 0.27-074; white women:
      odds ratio, 0.27, 95% confidence interval, 0.14-0.51). CONCLUSIONS: Differences
      in completing trastuzumab therapy were observed according to race and educational
      attainment among women who received treatment at National Comprehensive Cancer
      Network centers. Efforts to assure the appropriate use of trastuzumab and to
      understand treatment barriers are needed and may lead to improved outcomes. The
      authors report differences in the rate at which patients complete treatment with
      trastuzumab according to race and education among women who receive treatment at
      National Comprehensive Cancer Network centers. Efforts to assure the appropriate
      use of trastuzumab and to understand treatment barriers are needed and may lead
      to improved outcomes.

PMID- 23011925
TI  - Anti-obesity and hypolipidemic effects of Fuzhuan brick tea water extract in high
      fat diet-induced obese rats.
AB  - BACKGROUND: Fuzhuan brick tea is a kind of microbial fermented tea, which has
      received increasing attention in recent years owing to its benefits for human
      health. In this study, the anti-obesity and hypolipidemic effects of Fuzhuan
      brick tea water extracts (FTEs) were investigated. RESULTS: FTEs consisted of
      204.07 +/- 3.38 mg g(-1) polyphenol, 109.20 +/- 1.36 mg g(-1) flavonoids, and
      others. The FTEs significantly suppressed the increase of body weight and
      accumulation of adipose tissue, and reduced the level of serum triacylglycerol,
      total cholesterol and low-density lipoprotein (LDL) cholesterol in obese rats fed
      a high-fat diet. Moreover, FTEs attenuated the gene expression of sterol
      regulatory element binding protein-1c, fatty acid synthase and CCAAT/enhancer
      binding protein alpha, which is related to lipogenic metabolism. In contrast, the
      gene expressions of enzymes involved in energy expenditure and lipodieresis
      including hepatic peroxisome proliferator-activated receptor alpha, carnitine
      palmitoyltransferase 1a and LDL receptor gene expression were increased by FTE
      treatment. CONCLUSIONS: Our study demonstrates that FTEs have anti-obesity and
      hypolipidemic functions, suggesting that it might be effective for treatment of
      obesity and hyperlipemia.

PMID- 23011926
TI  - Human TRiC complex purified from HeLa cells contains all eight CCT subunits and
      is active in vitro.
AB  - Archaeal and eukaryotic cytosols contain group II chaperonins, which have a
      double-barrel structure and fold proteins inside a cavity in an ATP-dependent
      manner. The most complex of the chaperonins, the eukaryotic TCP-1 ring complex
      (TRiC), has eight different subunits, chaperone containing TCP-1 (CCT1-8), that
      are arranged so that there is one of each subunit per ring. Aspects of the
      structure and function of the bovine and yeast TRiC have been characterized, but
      studies of human TRiC have been limited. We have isolated and purified endogenous
      human TRiC from HeLa suspension cells. This purified human TRiC contained all
      eight CCT subunits organized into double-barrel rings, consistent with what has
      been found for bovine and yeast TRiC. The purified human TRiC is active as
      demonstrated by the luciferase refolding assay. As a more stringent test, the
      ability of human TRiC to suppress the aggregation of human gammaD-crystallin was
      examined. In addition to suppressing off-pathway aggregation, TRiC was able to
      assist the refolding of the crystallin molecules, an activity not found with the
      lens chaperone, alpha-crystallin. Additionally, we show that human TRiC from HeLa
      cell lysate is associated with the heat shock protein 70 and heat shock protein
      90 chaperones. Purification of human endogenous TRiC from HeLa cells will enable
      further characterization of this key chaperonin, required for the reproduction of
      all human cells.

PMID- 23011928
TI  - Immobilization of liposomes and vesicles on patterned surfaces by a peptide
      coiled-coil binding motif.
AB  - Patchy surfaces: An azide-terminated self-assembled monolayer was patterned with
      the peptide sequence (EIAALEK)(3) by using microcontact printing. This sequence
      forms stable coiled-coil heterodimers with the complementary peptide
      (KIAALKE)(3). By introducing this peptide to the surface of phospholipid
      liposomes and cyclodextrin vesicles, liposomes and vesicles can be immobilized at
      the patterned surface.

PMID- 23011932
TI  - miRNAs in cardiac disease: sitting duck or moving target?
AB  - Emerging findings indicate that cells can produce both micro (mi)RNAs and their
      messenger (m)RNA targets in multiple processing variants in a tissue- and
      developmental stage-selective manner. Specifically, we find that cells accumulate
      a greater range of functional miRNAs than hitherto expected, whereas mRNAs with
      alternative 3' untranslated regions that include varying numbers of miRNA target
      sites are also seen to be common. This has important implications for both our
      understanding of miRNA function in a given biological context and the design of
      successful strategies for experimental or therapeutic intervention. In this
      review, we relate these new phenomena to miRNAs in the heart, where they are
      known to play critical roles during normal function as well as in cardiac
      disease.

PMID- 23011927
TI  - Tissue-specific upregulation of HSP72 in mice following short-term administration
      of alcohol.
AB  - Oxidative stress and cellular injury have been implicated in induction of HSP72
      by alcohol. We investigated the association between HSP72 induction and oxidative
      stress in mouse tissues following short-term administration of high doses of
      alcohol and caffeine alone or in combination. Adult male C57BL/6J mice were
      gavaged with vehicle, alcohol (~1.7 g/kg/day), caffeine (~44 mg/kg/day), or
      alcohol plus caffeine once daily for ten consecutive days. Upon completion of the
      treatments, tissues were collected for structural and biochemical analyses.
      Alcohol alone caused mild to moderate lesions in heart, liver, and gastrocnemius
      muscle. Similar structural changes were observed following administration of
      alcohol and caffeine combined. Alcohol administration also led to decreased
      glutathione levels in all three tissues and reduced plasma superoxide dismutase
      capacity. In contrast, alcohol and caffeine in combination reduced glutathione
      levels only in liver and gastrocnemius muscle and had no effect on plasma
      superoxide dismutase. Significant elevations in HSP72 protein and mRNA and in
      HSF1 protein levels were noted only in liver by alcohol alone or in combination
      with caffeine. No significant changes in morphology and HSP72 were detected in
      any tissues tested following administration of caffeine alone. These results
      suggest that a redox mechanism is involved in the structural impairment caused by
      short-term high-dose alcohol. Oxidative tissue injury by alcohol may not be
      associated with tissue HSP72 induction. Induction of HSP72 in liver by alcohol is
      mediated at both the transcriptional and translational levels.

PMID- 23011933
TI  - Australopithecus sediba and the earliest origins of the genus Homo.
AB  - Discovered in 2008, the site of Malapa has yielded a remarkable assemblage of
      early hominin remains attributed to the species Australopithecus sediba. The
      species shows unexpected and unpredicted mosaicism in its anatomy. Several
      commentators have questioned the specific status of Au. sediba arguing that it
      does not exceed the variation of Au. africanus. This opinion however, does not
      take into account that Au. sediba differs from Au. africanus in both craniodental
      and postcranial characters to a greater degree than Au.africanus differs from Au.
      afarensis in these same characters. Au. sediba has also been questioned as a
      potential ancestor of the genus Homo due to the perception that earlier specimens
      of the genus have been found than the c198 Ma date of the Malapa sample. This
      opinion however, does not take into account either the poor condition of these
      fossils, as well as the numerous problems with both the criteria used to
      associate them with the genus Homo, nor the questionable provenance of each of
      these specimens. This argument also does not acknowledge that Malapa is almost
      certainly not the first chronological appearance of Au. sediba, it is only the
      first known fossil occurrence. Au. sediba should therefore be considered a strong
      potential candidate ancestor of the genus Homo until better preserved specimens
      are discovered that would refute such a hypothesis.

PMID- 23011934
TI  - Body dimensions and socioeconomic development: an introduction.

PMID- 23011935
TI  - An anthropometric history of the World, 1810-1980: did migration and
      globalization influence country trends?

PMID- 23011936
TI  - Climate, height and economic development in sub-Saharan Africa.

PMID- 23011937
TI  - Anthropological variables as economic indicators.

PMID- 23011938
TI  - Secular trend and regional differences in the stature of Italians.

PMID- 23011939
TI  - The trend of stature in pre-protohistoric Central-Southern Italy.

PMID- 23011940
TI  - The remarkable effect of the manganese ion with dioxygen on the stability of pi
      conjugated radical cations.
AB  - In this paper, nanosecond laser flash photolysis has been used to investigate the
      influence of metal ions on the kinetics of radical cations of a range of
      carotenoids (astaxanthin (ASTA), canthaxanthin (CAN), and beta-carotene (beta
      CAR)) and various electron donors (1,4-diphenyl-1,3-butadiene (14DPB), 1,6
      diphenyl-1,3,5-hexatriene (16DPH), 4-methoxy-trans-stilbene (4 MeOSt), and trans
      stilbene (trans-St)) in benzonitrile. Radical cations have been generated by
      means of photosensitized electron-transfer (ET) using 1,4-dicyanonaphthalene
      (14DCN) and biphenyl (BP). The kinetic decay of CAR(. +) shows a strong
      dependence on the identity of the examined metal ion. For example, whereas
      NaClO(4) has a weak effect on the kinetics of CAR(. +), Ni(ClO(4))(2) causes a
      strong retardation of the decay of CAR(. +). It is also interesting to note that
      Mn(2+), which is a biologically relevant metal ion, shows the strongest effect of
      all the investigated metal ions (e.g., in the presence of Mn(2+) ions, the half
      life (t(1/2)) of CAN(. +) (t(1/2) >90 ms) is more than three orders of magnitude
      higher than in the absence of the metal ions (t(1/2) ~16 MUs)). Furthermore, the
      influence of metal-ion and oxygen concentrations on the kinetics of CAR(. +)
      reveals their pronounced effect on the kinetic decay of CAR(. +). However, these
      remarkable effects are greatly diminished if either oxygen or metal ions are
      removed from the investigated solutions. Therefore, it can be concluded that
      oxygen and metal ions interact cooperatively to induce the observed substantial
      effects on the stabilities of CAR(. +). These results are the first direct
      observation of the major role of oxygen in the stabilization of radical cations,
      and they support the earlier mechanism proposed by Astruc et al. for the role of
      oxygen in the inhibition of cage reactions. On the basis of these results, the
      factors that affect the stability of radical cations are discussed and the
      mechanism that shows the role of oxygen and metal ions in the enhancement of
      radical-cation stability is described.

PMID- 23011941
TI  - Simultaneous measurement of urinary total nicotine and cotinine as biomarkers of
      active and passive smoking among Japanese individuals.
AB  - OBJECTIVES: Measuring urinary cotinine is a popular and established method of
      biologically monitoring exposure to tobacco smoke. However, the lower detection
      limit of cotinine often impedes the evaluation of passive (second-hand) smoking
      and this, together with unconverted nicotine, does not reflect actual levels of
      exposure. Furthermore, a portion of the Japanese population might have decreased
      ability to metabolize nicotine. The present study was therefore carried out to
      validate the simultaneous analysis of total concentrations of free nicotine and
      cotinine and their glucuronides to determine actual levels of voluntary and
      involuntary exposure to cigarette smoke. METHODS: Urine samples from 118 Japanese
      smokers and 117 non-smokers were analyzed using gas chromatography-mass
      spectrometry. Voluntary and involuntary smoking status was self-reported and
      workplace smoking restrictions were objectively evaluated. RESULTS: The
      integrated sum of all concentrations showed 2.2- and 2.4-fold higher total levels
      (free and glucuronide) of nicotine and cotinine relative to the free levels.
      Median (quartiles) of total nicotine and cotinine were 1635 (2222) and 3948
      (3512) ng/mL in smokers, and 3.5 (5.3) and 2.8 (4.2) ng/mL in non-smokers.
      Concentrations of urinary nicotine were higher than those of cotinine in 21 % of
      smokers and in 54 % of non-smokers. Nicotine and cotinine levels were
      significantly associated with a smoking habit, as well as being significantly
      associated with the workplace and home environments of non-smokers. CONCLUSIONS:
      The present method can monitor voluntary and involuntary exposure to tobacco
      smoke. Measuring total urinary nicotine levels might be useful for analyzing
      exposure to cigarette smoke among non-smokers.

PMID- 23011942
TI  - A new method for determining why length of life is more unequal in some
      populations than in others.
AB  - Why is there greater variability in individual longevity in some populations than
      in others? We propose a decomposition method designed to address that question by
      quantifying the effects of population differences in the spread, allocation, and
      timing of the principal causes of death. Applying the method to the United States
      and Sweden, we find that spread effects account for about two-thirds of the
      greater variance in age at death among American adults, meaning that two-thirds
      of the U.S.-Sweden difference would persist if the two countries differed only
      with respect to within-cause variance among adults. The remainder of the
      difference is due largely to allocation effects, with the greater incidence of
      homicides and fatal traffic accidents alone accounting for more than one-fourth
      of the greater variance in age at death among adults in the United States.

PMID- 23011943
TI  - Impact of road traffic deaths on expected years of life lost and reduction in
      life expectancy in Brazil.
AB  - The road traffic crash burden is significant in Brazil; calculating years of life
      lost and life expectancy reduction quantifies the burden of road traffic deaths
      to enable prioritization of this issue. Years of life lost and reduction in life
      expectancy were calculated using 2008 population/crash data from Brazil's
      ministries of health and transport. The potential for reduction in crash
      mortality was calculated for hypothetical scenarios reducing death rates to those
      of the best-performing region and age category. In Brazil, road traffic deaths
      reduce the at-birth life expectancy by 0.8 years for males and by 0.2 years for
      females. Many years of life lost for men and woman could be averted-270,733 and
      123,986, respectively-if all rates matched those of the lowest-risk region and
      age category. This study further characterizes the burden of motor vehicle deaths
      in Brazil and quantifies the potential health benefits of policies/interventions
      that reduce road traffic death rates to those of the best-performing
      subpopulations.

PMID- 23011944
TI  - Variability in tannin content, chemistry and activity in a diverse group of
      tannin containing sorghum cultivars.
AB  - BACKGROUND: Tannins are large polyphenolic polymers and are known to bind
      proteins, limiting their digestibility, but are also excellent antioxidants.
      Numerous studies investigating the functional properties of sorghum tannin have
      been conducted by comparing grain samples from different sorghum lines without
      considering the other intrinsic characteristics of the grain. The purpose of this
      study was to remove the confounding intrinsic factors present in the endosperm so
      the effect of the tannins could be evaluated utilizing a unique
      decortication/reconstitution procedure. RESULTS: The tannin content of the 14
      cultivars tested ranged from 2.3 to 67.2 catechin equivalents. The bran fractions
      were studied for their impact on protein binding and antioxidant capacity.
      Protein digestibility by pepsin ranged from 8% to 58% at the highest tannin level
      addition. Protein binding ranged from 3.11 to 16.33 g blue bovine serum albumin
      kg-1 bran. Antioxidant capacity ranged from 81.33 to 1122.54 umol Trolox
      equivalents g-1 bran. High-performance size-exclusion chromatography detailed
      molecular size distributions of the tannin polymers and relationship to tannin
      functionality. CONCLUSION: The tannin content and composition play a significant
      role in determining tannin functionality. These differences will allow for
      selections of high-tannin sorghums with consideration of the biological
      activities of the tannins.

PMID- 23011945
TI  - Hydroxide ion conducting antimony(V)-doped tin pyrophosphate electrolyte for
      intermediate-temperature alkaline fuel cells.

PMID- 23011947
TI  - How to get your article rejected.

PMID- 23011948
TI  - Synthesis and supramolecular studies of chiral boronated platinum(II) complexes:
      insights into the molecular recognition of carboranes by beta-cyclodextrin.
AB  - The synthesis and characterisation of a novel isomeric family of closo-carborane
      containing Pt(II) complexes ((R/S)-(1-4)?2 NO(3)) are reported. Related complexes
      (5?NO(3) and 6?NO(3)) that contain the 7,8-nido-carborane cluster were obtained
      from the selective deboronation of the 1,2-closo-carborane analogues. The
      corresponding water-soluble supramolecular 1:1 host-guest beta-cyclodextrin (beta
      CD) adducts ((R/S)-(1-4)?beta-CD?2 NO(3)) were also prepared and fully
      characterised. HR-ESI-MS experiments confirmed the presence of the host-guest
      adducts, and 2D-(1) H{(11)B} ROESY NMR studies showed that the boron clusters
      enter the beta-CD from the side of the wider annulus. Isothermal titration
      calorimetry (ITC) experiments revealed enthalpically driven 1:1 and higher-order
      supramolecular interactions between beta-CD and (R/S)-(1-4)?2 NO(3) in aqueous
      solution. A comparison of the predominate 1:1 binding mode established that the
      affinity of beta-CD for the guest molecule is mainly influenced by the pyridyl
      ring substitution pattern and chirality of the host, whilst the nature of the
      closo-carborane isomer also plays some role, with the most favourable structural
      features for beta-CD binding being the presence of the 4-pyridyl ring, 1,12-closo
      carborane, and an S configuration. The results reported here represent the first
      comprehensive calorimetric study of the supramolecular interactions between closo
      carborane compounds and beta-CD, and it provides fascinating insights into the
      structural features influencing the thermodynamics of this phenomenon.

PMID- 23011946
TI  - Next generation organelles: structure and role of germ granules in the germline.
AB  - Germ cells belong to a unique class of stem cells that gives rise to eggs and
      sperm, and ultimately to an entire organism after gamete fusion. In many
      organisms, germ cells contain electron-dense structures that are also known as
      nuage or germ granules. Although germ granules were discovered more than 100
      years ago, their composition, structure, assembly, and function are not fully
      understood. Germ granules contain non-coding RNAs, mRNAs, and proteins required
      for germline development. Here we review recent studies that highlight the
      importance of several protein families in germ granule assembly and function,
      including germ granule inducers, which initiate the granule formation, and
      downstream components, such as RNA helicases and Tudor domain-Piwi protein-piRNA
      complexes. Assembly of these components into one granule is likely to result in a
      highly efficient molecular machine that ensures translational control and
      protects germline DNA from mutations caused by mobile genetic elements.
      Furthermore, recent studies have shown that different somatic cells, including
      stem cells and neurons, produce germ granule components that play a crucial role
      in stem cell maintenance and memory formation, indicating a much more diverse
      functional repertoire for these organelles than previously thought.

PMID- 23011949
TI  - Present and potential applications of cellulases in agriculture, biotechnology,
      and bioenergy.
AB  - Cellulase (CEL) presently constitutes a major group of industrial enzyme based on
      its diverse ranges of utilization. Apart from such current and well-established
      applications-as in cotton processing, paper recycling, detergent formulation,
      juice extraction, and animal feed additives-their uses in agricultural
      biotechnology and bioenergy have been exploited. Supplementation of CELs to
      accelerate decomposition of plant residues in soil results in improved soil
      fertility. So far, applying CELs/antagonistic cellulolytic fungi to crops has
      shown to promote plant growth performance, including enhanced seed germination
      and protective effects. Their actions are believed mainly to trigger plant
      defense mechanisms and/or to act as biocontrol agents that mediate disease
      suppression. However, the exact interaction between the enzymes/fungi and plants
      has not been clearly elucidated. Under mild conditions, removal of plant cell
      wall polysaccharides by CELs for protoplast preparation results in reduced
      protoplast damage and increased viability and yields. CELs have recently shown
      great potential in enzyme aid extraction of bioactive compounds from plant
      materials before selective extraction through enhancing release of target
      molecules, especially those associated with the wall matrix. To date, attempts
      have been made to formulate CEL preparation for cellulosic-based bioethanol
      production. The high cost of CELs has created a bottleneck, resulting in an
      uneconomic production process. The utilization of low-cost carbohydrates, strain
      improvement, and gene manipulations has been alternatively aimed at reducing the
      cost of CEL production. In this review, we focus on and discuss current knowledge
      of CELs and their applications in agriculture, biotechnology, and bioenergy.

PMID- 23011950
TI  - Isolation and characterization of lactic acid bacteria from pobuzihi (fermented
      cummingcordia), a traditional fermented food in Taiwan.
AB  - Lactobacillus pobuzihii is a novel species which has been previously found in
      pobuzihi (fermented cummingcordia), a traditional fermented food in Taiwan.
      However, the lactic acid bacteria (LAB) microflora in pobuzihi has not been
      studied in detail. In this study, LAB from pobuzihi were isolated, identified,
      and characterized. A total of 196 LAB were isolated; 79 cultures were isolated
      from the sample collected from a manufacturing factory, 38 from pobuzihi samples
      collected from 4 different markets, and 79 from 2 fresh cummingcordia samples.
      These isolates were characterized phenotypically and then divided into eight
      groups (A to H) by restriction fragment length polymorphism analysis and
      sequencing of 16S ribosomal DNA. Lactobacillus plantarum was the most abundant
      LAB found in most samples during the fermentation of pobuzihi. On the other hand,
      Enterococcus casseliflavus and Weissella cibaria were, respectively, the major
      species found in the two fresh cummingcordia samples. A potential novel species
      or subspecies of lactococcal strain was found. In addition, seven L. plantarum
      and five W. cibaria strains showed inhibitory activity against the indicator
      strain Lactobacillus sakei JCM 1157(T). This is the first report describing the
      distribution and varieties of LAB existing in the pobuzihi during its
      fermentation process and the final product on the market.

PMID- 23011951
TI  - Estimation of the quantity of bacteria encapsulated in Lentikats Biocatalyst via
      phospholipid fatty acids content: a preliminary study.
AB  - The content of phospholipid fatty acids (PLFA) was determined in samples of
      polyvinyl alcohol lenses (Lentikats Biocatalyst, LB) with encapsulated Paracoccus
      denitrificans withdrawn during long-term denitrification experiments. The total
      PLFA content correlated highly with specific denitrification activities of LB as
      well as biomass estimation based on image analyses of microscopic photos. The
      results confirmed the applicability of PLFA determination for estimation of the
      amount of living encapsulated microbial biomass during biotechnological
      applications.

PMID- 23011952
TI  - Infections are a global issue: infection addresses global issues.
AB  - Infections are of unifying global concern, despite regional differences in
      disease epidemiology, clinical appearance and the instruments to tackle them. The
      primary aim of Infection is "to be a forum for the presentation and discussion of
      clinically relevant information on infectious diseases... from all over the
      world". To that end, and as a reflection of the global burden of infectious
      diseases, we intend to increase the number of high-quality contributions from
      authors addressing the aetiology, pathogenesis, diagnosis and treatment of
      infectious diseases from outside Europe and the affluent North (Chang et al.
      Infection 40:359-365, 2012; Misra et al. Infection 40:125-130, 2012). The
      Editorial Board of Infection envisages the journal as an interface between where
      infectious diseases meet and mix between "North and South"--i.e., the field of
      travel medicine--frequently functioning as a sentinel for altered/novel disease
      activities that are encountered as imported conditions. With the change in
      generation on the Editorial Board, Infection aims to expand the areas of tropical
      medicine, travel medicine and global health with its own section editors (GC and
      MPG). Contributions from outside Europe are actively encouraged.

PMID- 23011953
TI  - Clinical significance of infections caused by plasmid-mediated AmpC beta
      lactamases and extended-spectrum beta-lactamase-producing Escherichia coli.

PMID- 23011954
TI  - An advance in the chemical synthesis of homogeneous N-linked glycopolypeptides by
      convergent aspartylation.

PMID- 23011955
TI  - Exposure to violence, social information processing, and problem behavior in
      preschool children.
AB  - Understanding the mechanisms by which early risk factors for social maladjustment
      contribute to disruptive behaviors in social settings is vital to developmental
      research and practice. A major risk factor for social maladjustment is early
      exposure to violence, which was examined in this short-term longitudinal study in
      relation to social information processing (SIP) patterns and externalizing and
      internalizing behaviors in a sample of 256 preschool children. Data on exposure
      to violence were obtained via parent report, data on SIP were obtained via child
      interview, and data on child problem behavior were obtained via teacher report.
      Findings supported the hypothesis that, compared to children not exposed to
      violence, children reported to witness and/or experience violence are more likely
      to attribute hostile intent to peers, generate aggressive responses, and evaluate
      socially unaccepted responses (aggressive and inept) as socially suitable. The
      former were also found to exhibit higher levels of externalizing and
      internalizing behaviors. Finally, SIP mediated the link between exposure to
      violence and problem behavior thus supporting this study's general approach,
      which argues that the link between exposure to violence and children's problem
      behaviors are better understood within the context of their perceptions about
      social relationships.

PMID- 23011956
TI  - Cell volume regulation in mammalian oocytes and preimplantation embryos.
AB  - The earliest stages of preimplantation embryos are particularly sensitive to
      increased osmolarity, even within the physiological range. This sensitivity
      contributed to persistent developmental arrest, even when embryos were cultured
      in vitro in older, conditioned culture media, and seems to arise when embryos at
      the 1- and 2-cell stages accumulate inorganic ions used for cell volume
      homeostasis at too high a level, through activation of coupled Na(+)/H(+) and
      HCO(3)-/Cl(-) exchange. Such accumulation of inorganic ions can be disruptive
      since, above a certain level, the increased ionic strength disrupts cellular
      biochemistry and macromolecular functions and alters membrane potential. To
      counter this, embryos have evolved mechanisms of cell volume regulation that are
      unique to early preimplantation embryogenesis. The primary role of these is
      glycine accumulation via the GLYT1 transporter, with a secondary contribution by
      betaine accumulation via the SIT1 transporter. Independent cell-volume regulation
      first arises in the oocyte only after ovulation is triggered, when the strong
      oocyte-zona pellucida adhesion present in germinal vesicle stage oocytes in the
      ovarian follicle is released and GLYT1 becomes activated to begin accumulating
      glycine. Open questions still remain regarding how these processes are regulated.

PMID- 23011957
TI  - A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II
      trial in rheumatoid arthritis.
AB  - We describe a dose escalation procedure for a combined phase I/II clinical trial.
      The procedure is based on a Bayesian model for the joint distribution of the
      occurrence of a dose limiting event and of some indicator of efficacy (both
      considered binary variables), making no assumptions other than monotonicity.
      Thus, the chances of each outcome are assumed to be non-decreasing in dose level.
      We applied the procedure to the design of a placebo-controlled, sequential trial
      in rheumatoid arthritis, in each stage of which patients were randomized between
      placebo and all dose levels that currently appeared safe and non-futile. On the
      basis of data from a pilot study, we constructed five different scenarios for the
      dose-response relationships under which we simulated the trial and assessed the
      performance of the procedure. The new design appears to have satisfactory
      operating characteristics and can be adapted to the requirements of a range of
      trial situations.

PMID- 23011958
TI  - Electronic coupling between two amine redox sites through the 5,5'-positions of
      metal-chelating 2,2'-bipyridines.
AB  - Electron delocalization of new mixed-valent (MV) systems with the aid of lateral
      metal chelation is reported. 2,2'-Bipyridine (bpy) derivatives with one or two
      appended di-p-anisylamino groups on the 5,5'-positions and a coordinated
      [Ru(bpy)(2)] (bpy = 2,2'-bipyridine), [Re(CO)(3)Cl], or [Ir(ppy)(2)] (ppy = 2
      phenylpyridine) component were prepared. The single-crystal molecular structure
      of the bis-amine ligand without metal chelation is presented. The electronic
      properties of these complexes were studied and compared by electrochemical and
      spectroscopic techniques and DFT/TDDFT calculations. Compounds with two di-p
      anisylamino groups were oxidized by a chemical or electrochemical method and
      monitored by near-infrared (NIR) absorption spectral changes. Marcus-Hush
      analysis of the resulting intervalence charge-transfer transitions indicated that
      electron coupling of these mixed-valent systems is enhanced by metal chelation
      and that the iridium complex has the largest coupling. TDDFT calculations were
      employed to interpret the NIR transitions of these MV systems.

PMID- 23011960
TI  - Introduction: pharmacist role in pain management.

PMID- 23011959
TI  - Silymarin for HCV infection.
AB  - Silymarin, an extract of milk thistle seeds, and silymarin-derived compounds have
      been considered hepatoprotective since the plant was first described in ancient
      times. Hepatoprotection is defined as several non-mutually exclusive biological
      activities including antiviral, antioxidant, anti-inflammatory and
      immunomodulatory functions. Despite clear evidence for silymarin-induced
      hepatoprotection in cell culture and animal models, evidence for beneficial
      effects in humans has been equivocal. This review will summarize the current
      state of knowledge on silymarin in the context of HCV infection. The information
      was collated from a recent workshop on silibinin in Germany.

PMID- 23011961
TI  - Pharmacist's role in dispensing opioids for acute and chronic pain.
AB  - Pain continues to be a serious health care concern in the United States. Patients
      with chronic pain experience the impact of the disease throughout their lives
      including their social interactions, family relationships, and in many cases
      economic productivity. Multiple surveys have found that many pharmacists hold
      misconceptions regarding opioids, pain disease states, and their understandings
      of current regulations. Multiple barriers affect the ability of pharmacists to
      deliver care to patients' prescribed opioid therapy. Inadequate communication
      between health care professionals and patients is one of the hurdles, which
      prevents quality care. Increased communication between health care providers
      including access to health information is one step, which is crucial to improving
      provision of pharmacotherapy. Finally, the quality of educational opportunities
      relative to opioids and pain management specifically for pharmacists needs to be
      increased, and consideration needs to be given for making appropriate pain
      management education mandatory.

PMID- 23011962
TI  - Treatment strategies to overcome end-of-dose failure with oral and transdermal
      opioids.
AB  - Extended-release oral and transdermal opioids are increasingly being used for the
      management of chronic pain. Although the dosing intervals for these products were
      established through controlled clinical trials, expanded use of extended-release
      and transdermal dosage forms has resulted in awareness that a significant number
      of patients with chronic pain experience loss of baseline pain control prior to
      the next scheduled dose. End-of-dose failure (EDF) is the term used to describe
      this type of pain manifestation. By recognizing potential causes of EDF,
      strategies may be developed to overcome its occurrence to improve patients' pain
      control.

PMID- 23011963
TI  - Bioterrorism: pathogens as weapons.
AB  - Biowarfare has been used for centuries. The use of biological weapons in
      terrorism remains a threat. Biological weapons include infectious agents
      (pathogens) and toxins. The most devastating bioterrorism scenario would be the
      airborne dispersal of pathogens over a concentrated population area.
      Characteristics that make a specific pathogen a high-risk for bioterrorism
      include a low infective dose, ability to be aerosolized, high contagiousness, and
      survival in a variety of environmental conditions. The most dangerous potential
      bioterrorism agents include the microorganisms that produce anthrax, plague,
      tularemia, and smallpox. Other diseases of interest to bioterrorism include
      brucellosis, glanders, melioidosis, Q fever, and viral encephalitis. Food safety
      and water safety threats are another area of concern.

PMID- 23011964
TI  - Why should you be a member, you ask? (Hint: It isn't always about the CE.).

PMID- 23011965
TI  - False hope?

PMID- 23011967
TI  - Better quality.

PMID- 23011966
TI  - Poison fighters.

PMID- 23011968
TI  - Wrongfully accused.

PMID- 23011969
TI  - Mechanism of formation of palladium nanoparticles: Lewis base assisted, low
      temperature preparation of monodisperse nanoparticles.
AB  - Small and cool: The mechanism of formation of amine-capped Pd nanoparticles from
      [Pd(acac)(2)] (acac=acetylacetonate) is elucidated, and shown to involve Pd-amido
      and Pd-hydride intermediates. The addition of a Lewis base results in a
      significant reduction in the temperature at which highly monodisperse
      nanoparticles are isolated.

PMID- 23011970
TI  - The relationship between relative deprivation and adult nutritional status in
      rural Zambia.
AB  - OBJECTIVES: To explore statistically the relationship between adult short-run
      nutritional status [body mass index (BMI)] and a measure of relative deprivation
      [subjective socioeconomic status (SES)] using panel data collected in a
      developing country where there is a high degree of poverty and a very uneven
      distribution of income. METHODS: Study participants included men and women from a
      random sample of households located in a rural setting in Zambia. The data were
      collected during two waves of survey interviews in 2009. A multilevel model was
      used to estimate the relationship between subjective SES and adult BMI and
      controlled for individual absolute income as well as other correlates of adult
      health. The sample size included 254 observations. RESULTS: A positive
      relationship was established between individual absolute income and adult BMI at
      the 1% level. A negative and statistically significant association was found at
      the 1% level between lower subjective SES and adult BMI. Lower perception of
      place within the socioeconomic hierarchy was on average associated with a 0.44
      decrease in adult BMI. CONCLUSIONS: This study found that, independent of
      individual absolute income, lower subjective SES was negatively related with
      adult BMI in rural Zambia. The result provides evidence that lower perception of
      place within the local socioeconomic hierarchy matters to health. Future studies
      should continue exploring the relationship between subjective and objective
      measures of relative deprivation and health in developing countries, where the
      bulk of the research focuses on material not relative deprivation as a key
      determinant of individual health.

PMID- 23011973
TI  - Structural studies on 4,5-disubstituted 2-aminoimidazole-based biofilm modulators
      that suppress bacterial resistance to beta-lactams.
AB  - A library of 4,5-disubstituted 2-aminoimidazole triazole amide (2-AITA)
      conjugates has been successfully assembled. Upon biological screening, this class
      of small molecules was discovered as enhanced biofilm regulators through non
      microbicidal mechanisms against methicillin-resistant Staphylococcus aureus
      (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB), with active
      concentrations in the low micromolar range. The library was also subjected to
      synergism and resensitization studies with beta-lactam antibiotics against MRSA.
      Lead compounds were identified that suppress the antibiotic resistance of MRSA by
      working synergistically with oxacillin, a beta-lactam antibiotic resistant to
      penicillinase. A further structure-activity relationship (SAR) study on the
      parent 2-AITA compound delivered a 2-aminoimidazole diamide (2-AIDA) conjugate
      with significantly increased synergistic activity with oxacillin against MRSA,
      decreasing the MIC value of the beta-lactam antibiotic by 64-fold. Increased anti
      biofilm activity did not necessarily lead to increased suppression of antibiotic
      resistance, which indicates that biofilm inhibition and resensitization are most
      likely occurring via distinct mechanisms. 

PMID- 23011974
TI  - Energy propagation through a protometabolism leading to the local emergence of
      singular stationary concentration profiles.
AB  - Living systems rely on chains of energy transfer from an energy source to
      maintain their metabolism. This task requires functionally identified components
      and organizations. However, propagation of a sustained energy flux through a
      cascade of reaction cycles has never been reproduced at a steady state in a
      simple chemical system. By using energy patterning and a diffusing hub reactant,
      we achieved the transfer of energy through an abiotic protometabolism. Patterned
      illumination was applied to a liquid solution of a reversible photoacid. It
      resulted in the local onset of a proton pump, which subsequently drove an
      extended reaction-diffusion cycle that involved pH-sensitive reactants. Thus,
      light has been used for locally setting out of chemical equilibrium a reaction
      involving "blind" reactants. The spontaneous onset of an energy-transfer chain
      notably drives the local generation of singular dissipative chemical structures;
      continuous matter fluxes are dynamically maintained at boundaries between
      spatially and chemically segregated zones, in the absence of any membrane or
      predetermined material structure.

PMID- 23011976
TI  - Standards in medical education and gcc countries.

PMID- 23011975
TI  - Astrocytic Fas ligand expression is required to induce T-cell apoptosis and
      recovery from experimental autoimmune encephalomyelitis.
AB  - In T-cell-mediated autoimmune diseases of the CNS, apoptosis of Fas(+)  T cells
      by FasL contributes to resolution of disease. However, the apoptosis-inducing
      cell population still remains to be identified. To address the role of astrocytic
      FasL in the regulation of T-cell apoptosis in experimental autoimmune
      encephalomyelitis, we immunized C57BL/6 glial fibrillary acid protein (GFAP)-Cre
      FasL(fl/fl)  mice selectively lacking FasL in astrocytes with MOG(35-55) 
      peptide. GFAP-Cre FasL(fl/fl)  mice were unable to resolve EAE and suffered from
      persisting demyelination and paralysis, while FasL(fl/fl)  control mice
      recovered. In contrast to FasL(fl/fl)  mice, GFAP-Cre FasL(fl/fl)  mice failed to
      induce apoptosis of Fas(+)  activated CD4(+)  T cells and to increase numbers of
      Foxp3(+)  Treg cells beyond day 15 post immunization, the time point of maximal
      clinical disease in control mice. The persistence of activated and GM-CSF
      producing CD4(+)  T cells in GFAP-Cre FasL(fl/fl)  mice also resulted in an
      increased IL-17, IFN-gamma, TNF, and GM-CSF mRNA expression in the CNS. In vitro,
      FasL(+)  but not FasL(-)  astrocytes induced caspase-3 expression and apoptosis
      of activated T cells. In conclusion, FasL expression of astrocytes plays an
      important role in the control and elimination of autoimmune T cells from the CNS,
      thereby determining recovery from EAE.

PMID- 23011977
TI  - Breastfeeding practice among women attending primary health centers in riyadh.
AB  - OBJECTIVES: (1) To study the patterns of breastfeeding of last children,
      duration, factors and reasons for it. (2) To study the factors affecting
      breastfeeding among mothers who are breastfeeding and the reasons for continuing
      or failure to continue, at the primary health care centers (PHC) in Riyadh.
      METHOD: A cross-sectional study was conducted by distributing 1000 questionnaires
      in 10 PHC centers. The breastfeeding practices were categorized on WHO terms.
      RESULTS: Most of the studied last children (95.1%) were breastfed. Exclusive
      breastfeeding rate from birth was 62.9%, for up to four months was 13.2% and for
      six months was 3.3% . The mixed breastfeeding rate from birth was 32.2%, up to
      age of four months was 53.1% and for children more than six months old it was
      20.3%. The mean age of the introduction of solid food was 4.6 +/-1.4 months.
      Artificial feeding rate was 4.9% at birth , 30.3% up to four months and 49.7% for
      children more than six months old. The most frequent reason for the continuation
      of breastfeeding was Quranic instruction (55.1%) and its failure was inadequate
      milk (60.8%). The exclusive breastfeeding and the duration of breastfeeding had
      statistically significant association with the mothers' residence, marital
      status, number of children alive, occupation and the level of education. In
      addition, there was significant association of exclusive breastfeeding and the
      non-introduction of artificial feeding at the hospital but not with health
      education on breastfeeding at the centers . RECOMMENDATIONS: To promote the
      education of mothers on breastfeeding, promote the training of PHC center health
      professionals and modify the policy of hospitals in the Kingdom on the feeding of
      newborns.

PMID- 23011978
TI  - Health education needs for pregnancy: a study among women attending primary
      health centers.
AB  - OBJECTIVE: To find out the level of health awareness related to pregnancy and the
      sources of information among parous women visiting the Primary Health Centers in
      Al- Khobar. METHODS: This is a cross-sectional study conducted at three Primary
      Health Centers in Al-Khobar during a two-week period in April 2001. Five hundred
      and eighty one parous women who were eligible for the study were interviewed with
      the help of a questionnaire. RESULTS: A large proportion of the women were well
      informed about certain health issues of pregnancy such as dietary intake of
      essential foods like dairy products (74.7%), Protein-rich foods (71.4%) and
      fruits (68.2%), the hours of daily rest necessary (81.9%), the need for exercise
      (83.6%), the importance and timing of antenatal visits, the risk of smoking in
      pregnancy (99.3%) and proper spacing of babies (97.7%). However, many women had
      no knowledge of the importance of taking high-fiber foods (55.1%) to avoid
      constipation, the required dietary changes in early pregnancy to prevent nausea
      and vomiting, and the ill-effects of maternal smoking on the fetus, Rubella
      infection and advancing maternal age on the fetus. They were also not aware of
      the importance of the various antenatal procedures such as blood examination,
      breast-care during pregnancy and immunizations to prevent Tetanus and Rubella
      infection. A higher literacy level of the women was significantly correlated with
      better knowledge on certain health parameters. Physicians and nurses constituted
      poor sources of health information (35.6%). CONCLUSION: There is a need to
      restructure the Health Education programmes relating to pregnancy delivered
      through PHCs and the mass media for better knowledge among women of childbearing
      age can decrease pregnancy-related problems and improve perinatal outcome.

PMID- 23011979
TI  - WHAT DO PATIENT's EXPECT OF THEIR GENERAL PRACTITIONERS?
AB  - OBJECTIVE: To explore patient's expectations before consulting their general
      practitioners (GPs) and determine the factors that influence them. METHODS: A
      cross sectional survey was carried out in five primary care centers representing
      different areas of Riyadh city, Saudi Arabia using a self-administered
      questionnaire distributed to patients before consulting general practitioners. A
      sample of 944 Saudi patients was randomly selected. RESULTS: 74.6% preferred
      Saudi doctors, and 92.6% would like to have more laboratory tests for the
      diagnosis of their illnesses. More than two third of the patients (78.0%) felt
      entirely comfortable when talking with GPs about the personal aspects of their
      problems. About half thought that the role of GP was mainly to refer patients to
      specialists, while 55.2% believed that the GP cannot deal with the psychosocial
      aspect of organic diseases. The commonest reason for consulting GPs was for a
      general check up. CONCLUSION: The GP has to explore patients' expectations so
      that they can either be met or their impracticality explained. GPs should search
      for patient's motives and reconcile this with their own practice. GP should be
      trained to play the standard role of Primary Care Physician.

PMID- 23011980
TI  - A spectrum of pathogenic and non-pathogenic intestinal parasites in pre
      employment medical check-up for workers and their families.
AB  - INTRODUCTION: Stool analysis plays an important role in pre-employment tests for
      the screening of intestinal parasites in new workers. OBJECTIVE: to explore the
      spectrum of intestinal parasites in stool samples of workers and their families
      during the pre-employment tests over a one-year period at King Abdulaziz
      University Hospital (KAUH). METHODS: Subjects were selected sequentially from
      routine single stool analysis forms labeled for pre-employment tests. Stool
      specimens were examined using the formalin ether technique at the parasitology
      laboratory at KAUH. RESULTS: Two hundred and ninety two different stool samples
      of the workers and their families were studied. Their ages ranged from 3 to 72
      year old (mean 32 +/- 8.5 SD) and females formed 58.6% of the number. Intestinal
      parasites were detected in 161 workers (55%). The prevalence of intestinal
      parasites in Saudi workers was significantly lower than non-Saudi nationals,
      15.8% versus 57.9% (p<0.001). Of all the positive cases, pathogenic intestinal
      parasites were found in 40 % of them and the commonest were Trichuris trichuria
      (39.1%), Hookworm (34.2%), Entamoeba histolytica (16.1%). Non-pathogenic
      parasites were found in 19.5% and the commonest were Blastocystis hominis
      (34.8%), Endolimax nana (29.8%), Entamoeba coli (15.5%). One type of parasite was
      found in 75 (46.6%) and multiple different parasites were found in 86 (53.4%).
      There was a high significant correlation between the detection of pathogenic and
      non-pathogenic parasites (p<0.001). CONCLUSION: Infestation of stools with
      pathogenic and non-pathogenic intestinal parasites is a common finding in more
      than half of the new workers and their families. The correlation between non
      pathogenic and pathogenic parasites reflects mutual risk factors, and their
      potential hazards cannot be overlooked. Effective stool screening and eradication
      strategies for intestinal parasites in new workers should be rigorously enforced.

PMID- 23011981
TI  - Clinical presentation of hypothyroidism.
AB  - OBJECTIVE: This study was to review the common and unusual symptoms of
      hypothyroidism. METHOD: A retrospective study was done of forty thousand patients
      attending Sultan Qaboos University Health Center (SQU), within a period of three
      years. Sixty-three patients proved to have either clinical or subclinical
      hypothyroidism and were screened for the different symptoms & signs of
      hypothyroidism. RESULTS: The well-known symptoms and signs of hypothyroidism
      reported in the medical textbooks were uncommon in this study. Symptoms such as
      dysarthria and dysphagia not usually mentioned in the medical textbooks were
      reported. CONCLUSION: Early diagnosis by screening both middle-aged as well as
      older patients is advantageous.

PMID- 23011982
TI  - Tourist satisfaction with primary health care services in aseer region.
AB  - OBJECTIVE: The objective of this study was to assess the satisfaction of tourists
      who utilized health care services of five selected primary health care centers in
      Abha, Aseer region of Saudi Arabia in the summer of the year 2000. METHODS: This
      study was conducted during July of 2000 in five primary health care centers
      (PHCCs) in Aseer region, Saudi Arabia. Self-administered questionnaire designed
      by the investigators was distributed to all tourists who fulfilled the following
      criteria: aged above 15 years, can read and write and has intent on participating
      voluntarily. The questionnaire concerned satisfaction with different health care
      services delivered by the PHCCs and suggestions for the improvement of the
      services. Data was entered and analyzed using SPSS. RESULTS: A total of 413
      tourists fulfilled the selected criteria. The mean age of the participants was
      29.2 years; 81.4% were males, 37.3% were highly educated and 32.7% came from
      western province. PHCCs services were accessible to 87% and the working hours at
      PHCCs were suitable for 88.6% of the tourists. More than three-quarters of the
      visitors came for cure. Satisfaction with the different health services on a 5
      point scale ranged from 4.63 points for availability of medications to 4.85
      points for cooperation of treating doctors. Seventeen suggestions and comments
      were reported by 26% of the participants. Most of these suggestions and comments
      were about providing an adequate number of female doctors and medications.
      CONCLUSION: This study revealed that most of the tourists who utilized the
      selected PHCCs in Aseer region were satisfied with most of the different PHCCs
      services. However, many tourists gave valid suggestions and comments which should
      be considered for the improvement of the quality of care in these PHCCs in the
      future.

PMID- 23011983
TI  - Application of information and communication technologies in medical education.
AB  - The recognition that information and communication technologies should play an
      increasingly important role in medical education is a key to educating physicians
      in the 21(st) century. Computer use in medical education includes, Internet
      hypermedia/multimedia technologies, medical informatics, distance learning and
      telemedicine. Adaptation to the use of these technologies should ideally start
      from the elementary school level. Medical schools must introduce medical
      informatics courses very early in the medical curriculum. Teachers will need
      regular CME courses to prepare and update themselves with the changing
      circumstances. Our infrastructure must be prepared for the new developments with
      computer labs, basic skill labs, close circuit television facilities, virtual
      class rooms, smart class rooms, simulated teaching facilities, and distance
      teaching by tele-techniques. Our existing manpower including, doctors, nurses,
      technicians, librarians, and administration personal require hands-on training,
      while new recruitment will have to emphasize compulsory knowledge of and
      familiarity with information technology. This paper highlights these subjects in
      detail as a means to prepare us to meet the challenges of the 21(st) century.

PMID- 23011985
TI  - Enantioselective total synthesis of the diterpene (+)-cubitene.

PMID- 23011986
TI  - Evolution of a new medical school: goals and challenges.

PMID- 23011984
TI  - Modified Phemister procedure for the surgical treatment of Rockwood types III,
      IV, V acute acromioclavicular joint dislocation.
AB  - Acromioclavicular (AC) joint dislocations are common in young, active patients.
      In case of surgical indications, Rockwood type IV, type V and selected type III
      dislocation, we use modified Phemister procedure. At mid-term follow-up, by an
      average of 35.1 months, we reassessed the records of 14 patients surgically
      treated for acute AC dislocation from February 2007 to November 2010. In patients
      with a diagnosis of grade III lesion, indication for surgery was given on the
      basis of the patient's functional demand. Full recovery was obtained on average 3
      months after surgery. Constant Score accounted for 92.7 points, mean Disabilities
      of the Arm, Shoulder and Hand Score for 3.2 points, and mean Simple Shoulder Test
      Score for 11.4 points. X-ray findings were partial loss of reduction (9 cases),
      subclinic re-dislocation (2 cases), calcification (5 cases) and post-traumatic
      arthritis (2 cases). Modified Phemister is a reliable technique, technically
      easy, a low learning curve procedure and cheap with low hardware's costs.

PMID- 23011987
TI  - Evidence based medicine: an overview.
AB  - Evidence based medicine (EBM) considered one of the most important developments
      in the practice of medicine in recent years, has evolved as a tool for improving
      the quality of health care. Several studies have shown EBM to be safe and cost
      effective. Physicians have welcomed EBM and shown a positive attitude toward it
      and have expressed desire to learn more about it. This is consistent in most
      studies done in different countries. However, some studies found considerable
      misunderstanding about terms and websites used in EBM. The major barriers to the
      practice of EBM perceived by physician in different studies include insufficient
      time and evidence, patients' preference and financial constraints. Training has
      been found to be conducive to the implementation and promotion of EBM. Some Arab
      countries are already implementing EBM and plan to include it in the
      undergraduate curriculum. In Saudi Arabia EBM was introduced in the late 90's and
      a National EBM Advisory Board was formed.

PMID- 23011988
TI  - Short-term outcome of preterms in two neonatology units in Al-qassim, saudi
      arabia.
AB  - OBJECTIVE: A follow-up study, to compare the short-term outcome of preterms, in
      two hospitals in Al Qassim region, Saudi Arabia. METHODS: Preterms admitted in
      two hospitals, 47 in hospital A and 36 in hospital B, were followed from
      admission until one month after discharge. Preterms were compared on gestational
      age, birth weight, birth head circumference and length of stay. Outcome measures
      were weight gain per day, feeding patterns on discharge and feeding patterns one
      month after discharge compared with the feeding of normal infants (200 infants)
      at the age of 6 weeks. RESULTS: No difference was found between the two hospitals
      on admission in gestational age, mean birth weight, birth head circumference and
      length of stay. Mean weight gain per day was significantly higher in hospital A,
      9.56 (+/- 19.7) gm, compared to 1.22 (+/- 29.47) gm in hospital B. (P=0.049). But
      the proportion of exclusive breast fed infants, one month after discharge was
      higher in hospital B, 37.5% compared to 13.2% in hospital A. (p=0.0224).
      CONCLUSION: Our study showed that there is a clear hospital level difference in
      the same region, in the short-term outcome. This emphasizes that outcome should
      be continuously followed and that differences should be evaluated in perinatal
      audit procedure.

PMID- 23011989
TI  - Prevalence of minor psychiatric morbidity among female teachers in girls
      secondary schools in tabuk city, saudi arabia.
AB  - OBJECTIVES: Teachers are at the risk of developing minor psychiatric morbidity
      (MPM) because of the stressfulness of their job. This may lead to a significant
      decrease in their teaching effectiveness and to the development of serious health
      problems, if not detected early and managed appropriately. The objectives of this
      study were to determine the prevalence of MPM among female teachers in girls'
      secondary schools in Tabuk, and to analyze certain important associated
      demographic characteristics. METHODS: This was a cross-sectional study. First, a
      proportional cluster sample was selected randomly from the three sectors of
      schools in Tabuk, from which female teachers (198 out of a total of 517) in the
      selected schools were included in the study. Data on MPM and demographic
      characteristics were collected by means of the General Health Questionnaire 30
      (GHQ30), a validated and extensively used instrument for identifying MPM 
      RESULTS: Out of 198 participants, 187 completed the GHQ30 giving a response rate
      of 94.4%. The prevalence of MPM among them was 59.4% (111 participants). The
      variables with a statistically significant association with MPM were as follows:
      young age, nationality, positive participant psychiatric history, family history
      of medical and/or psychiatric problems, and divorced and widowed. No
      statistically significant associations were found with participants' medical
      problems or their mental status, either single or married, housing type, monthly
      income, the number of children in a family, and the number of family members.
      CONCLUSION: The finding of a high prevalence of MPM (59.4%) indicates that all
      participants may be at risk. Hence, appropriate and timely management, as well as
      social support are needed. Studies focusing on the causes and how to manage them
      will also be required.

PMID- 23011990
TI  - Newly diagnosed seizures in adolescents: a comparative study.
AB  - OBJECTIVE: To study the clinical, EEG and CT profile in a hospital population of
      adolescents with newly diagnosed recurrent seizures. METHODS: The clinical
      profiles obtained from history including detailed descriptions of the seizures,
      examination, electroencephalographic (EEG) and computed tomography (CT) findings
      were recorded prospectively for all 14 to18-year-old patients who were referred
      to the electrodiagnostic service at King Fahd Hospital of the University, Al-
      Khobar, Eastern Province, Saudi Arabia from 1(st) January 1996 to 31(st) December
      1997. The data were entered into a standard dbase file and analyzed using a
      personal computer. The results were compared with 2 previous concomitant subsets
      of data obtained from 263 children <=13 years (72%) and 73 adults > 18 years
      (20%) over the same study period. RESULTS: Twenty-nine patients (14 males and 15
      females, a mean age of 15.7 years) with newly diagnosed recurrent seizures were
      studied. A positive family history of seizures was found in 10.3%. The main
      seizure types were partial in 11 (37.9%), partial with secondary generalization
      in 6 (20.7%) and generalized in 12 (41.4%). The types of epileptic syndromes
      included localization-related 15 (51.7%), generalized 12 (41.4%) and undetermined
      2 (16.9%). The EEG was abnormal in 21 (72.4%) with epileptiform activity, focal
      in 11 (52.4%), generalized in 9 (42.8%) and none-epileptiform activity in 1
      (4.8%). The cranial CT findings were normal in 21 patients (72.4%) and abnormal
      in 8 (27.6%) patients, with focal lesions in 6 (75%) and generalized cerebral
      atrophy in 2 (25%). The frequency of adolescents presenting with newly-diagnosed
      seizures was 8% of the total study population of 365 patients including children
      and adults. CONCLUSION: The results showed that partial and partial with
      secondary generalization seizures and the localization-related epileptic syndrome
      are the most frequent seizure and epileptic syndrome types in adolescents. The
      least frequent of newly diagnosed seizures in adolescents compared to children
      and adults confirms the bimodality of peak frequency in the young and old that
      has been observed in the west.

PMID- 23011991
TI  - Depressive disorders in psychiatric outpatient clinic attendees in eastern saudi
      arabia.
AB  - BACKGROUND: Depressive disorders are common in Psychiatry Outpatient Clinics.
      PATIENTS: All new patients attending the Psychiatry Clinics at King Fahd Hospital
      of the University (KFHU), in the Eastern Province were included in the study.
      AIM: To investigate the frequency and pattern of depressive disorders among
      Psychiatric Out-patients attendees in the KFHU. METHODS: A semi-structured
      psychiatric interview and clinical mental state examination were used in the
      assessment of all consecutive new patients attending the clinic during the study
      period. The Psychiatric diagnoses were made according to the 10(th) Edition of
      International Classification of Mental and Behavioral Disorders (ICD-10).
      RESULTS: The frequency of depressive disorders was 19.3%. The majority of the
      patients were between 20-49 years of age and females predominated in the ratio of
      1.7:1. Almost 70% were formally unemployed (including 66 housewives). Depressive
      disorder of the moderate nature was the commonest. CONCLUSION: Depressive
      disorders are common in Psychiatry outpatients. The socio-demographic
      characteristics of depressive disorder in the Kingdom of Saudi Arabia are similar
      to those abroad in many respects.

PMID- 23011992
TI  - Prevalence of obesity among type 2 diabetic patients in Al-khobar primary health
      care centers.
AB  - OBJECTIVES: This study estimates the prevalence of obesity among Type 2 diabetic
      patients who are followed in mini clinics (hypertension, diabetes) in Primary
      Health Care Centers (PHCC) in Al-Khobar. METHODS: Retrospective study reviewing
      all diabetic patient files registered in PHC centers in the Al- Khobar area from
      May 2000 to October 2001. RESULTS: Of the 382 diabetic patients followed in PHC,
      88.7% were type 2 diabetics, and according to WHO classification of obesity 0.7%
      were underweight. Only 21.8% of type 2 diabetic patients were in their ideal
      range of body weight. While 31.2% were overweight (BMI in the range of 25.0-29.9
      kg/m(2)), 39.9% of the type 2 diabetic patients were found to be obese (BMI= 30 -
      39.9 kg / m(2)), and 6.3% had morbid obesity (BMI >= 40 kg / m(2)). CONCLUSION:
      High prevalence of overweight and obesity in type 2 diabetics is associated with
      other serious complications. This study emphasizes the importance of training
      health care providers for the proper follow-up of patients.

PMID- 23011993
TI  - Hypothyroidism presenting with dysarthria.
AB  - Hypothyroidism is a common endocrine disorder with characteristic clinical
      symptoms and signs. Typical symptoms of hypothyroidism are lethargy, cold
      intolerance, slowing of intellectual and motor activity, decreased appetite,
      weight gain, and dry skin. A 39-year-old female presented to the clinic with
      dysarthria as the chief symptom. Subsequent questions revealed that other
      symptoms were confined to the otolaryngeal region, which were episodes of mild
      dysphonia, dysphagia, sleep apnea, and snoring. Laboratory data revealed marked
      hypothyroidism and positive tests for antithyroglobulin and antimicrosomal
      antibodies. After administration of thyroxin, the dysarthria and the other
      symptoms rapidly disappeared. Dysarthria may be the presenting symptom of
      hypothyroidism and can be resolved after hormone replacement therapy.

PMID- 23011994
TI  - Removal of a deeply migrated pancreatic stent in a normal-size pancreatic duct
      using a modified snare with a cut plastic sheath.

PMID- 23011995
TI  - Pericecal abscess treated by endoscopic transappendiceal stenting.

PMID- 23011996
TI  - Exchange of self-expandable metal stent in endoscopic ultrasound-guided
      hepaticogastrostomy.

PMID- 23011997
TI  - Fatal perforation with subcutaneous emphysema complicating ERCP.

PMID- 23011998
TI  - Extrahepatic bile duct polyp mimicking biliary parasitic disease.

PMID- 23011999
TI  - Malignant esophagobronchial fistula with severe esophageal stenosis, successfully
      treated by transbronchial occlusion with cyanoacrylate glue.

PMID- 23012000
TI  - Placement of an esophageal self-expandable metal stent through a percutaneous
      endoscopic gastrostomy tract, for endoscopic therapy of upper gastrointestinal
      bleeding.

PMID- 23012001
TI  - Meckel's ileitis versus Crohn's ileitis: diagnosis using balloon enteroscopy.

PMID- 23012002
TI  - Hemoclip retained for more than 2 years.

PMID- 23012003
TI  - Extractible self-expandable metal stent in the treatment of Crohn's disease
      anastomotic strictures.

PMID- 23012004
TI  - Endoscopic ultrasound-guided gold fiducial marker placement for intraoperative
      identification of insulinoma.

PMID- 23012005
TI  - Endoscopic ultrasound-guided transgastric biliary metal stent placement after
      dilation with tapered-tip Teflon catheters and marking with a clip.

PMID- 23012006
TI  - Recurrent rectosigmoid volvulus and fatal peritonitis after percutaneous
      endoscopic sigmoidostomy.

PMID- 23012007
TI  - Upper gastrointestinal endoscopy for hematemesis in a patient aged 117 years.

PMID- 23012008
TI  - Endoscopic submucosal dissection using endoclips to assist in mucosal flap
      formation (novel technique: "clip flap method").

PMID- 23012009
TI  - Hemosuccus pancreaticus caused by in situ carcinoma of the pancreas.

PMID- 23012010
TI  - Endoscopic resection of a large colonic leiomyosarcoma.

PMID- 23012011
TI  - Intraluminal injection of indigo carmine facilitates identification of the
      afferent limb during double-balloon ERCP.

PMID- 23012012
TI  - Perianal embryonal rhabdomyosarcoma diagnosed by endoscopic ultrasound-guided
      fine needle aspiration.

PMID- 23012013
TI  - Double somatostatinoma and double papillectomy in a patient with type 1
      neurofibromatosis (von Recklinghausen's disease).

PMID- 23012014
TI  - Cytomegalovirus colitis in a case of cryptogenic colitis.

PMID- 23012015
TI  - Hepatic penetration by stomal ulcer: rare complication of a peptic ulcer.

PMID- 23012016
TI  - Endoscopic removal of localized gastric amyloidosis.

PMID- 23012017
TI  - Esophageal self-expanding metallic stent (SEMS) migration: it's a topsy-turvy
      world.

PMID- 23012018
TI  - Gastroduodenal ulceration after selective internal radiation therapy of liver
      tumor.

PMID- 23012019
TI  - Tissue hyperplasia following placement of a biodegradable stent for a refractory
      esophageal stricture: treatment with argon plasma coagulation.

PMID- 23012020
TI  - Confocal laser endomicroscopy for the diagnosis of diversion colitis.

PMID- 23012021
TI  - An unusual case of jejunal choriocarcinoma detected by single-balloon endoscopy.

PMID- 23012022
TI  - Triple pylorus.

PMID- 23012023
TI  - Anterior arytenoid cartilage dislocation, a rare complication of
      esophagogastroduodenoscopy.

PMID- 23012024
TI  - Duodenal stump fistula following Roux-en-Y gastrectomy, treated with single
      balloon enteroscopy using the tulip bundle technique and fibrin glue injection.

PMID- 23012025
TI  - Gastric necrosis following intragastric balloon placement: urgent sleeve
      gastrectomy as a rescue and definitive procedure.

PMID- 23012026
TI  - Large-bowel obstruction caused by pancreatic tail cancer.

PMID- 23012027
TI  - Successful management of arterial bleeding complicating endoscopic ultrasound
      guided cystogastrostomy using a covered metallic stent.

PMID- 23012028
TI  - A new anchoring technique for accessing the bile duct during direct peroral
      cholangioscopy using the guide probe of Kautz.

PMID- 23012029
TI  - Pharyngeal webs in a patient with dysphagia and Behcet's disease.

PMID- 23012030
TI  - Rectal band ligation for treatment of extensive chronic hemorrhagic radiation
      proctitis.

PMID- 23012031
TI  - High-intensity focused ultrasound liver destruction through the gastric wall
      under endoscopic ultrasound control: first experience in living pigs.

PMID- 23012032
TI  - The medical profession: the bright past and future challenges.

PMID- 23012033
TI  - Can a short-term training course improve the primary-care physicians' attitudes
      toward mental health problems?
AB  - OBJECTIVE: To measure changes in the attitude of Primary Health Care (PHC)
      physicians towards mental illnesses after a short-term training course. In
      addition, to ascertain if this change would persist 6 months after the training
      course. METHOD: This is an intervention type study. Out of 296 PHC physicians
      working in Eastern Saudi Arabia, 191 were randomly selected and divided randomly
      into two groups. The Study groups were tested for pre and post exposure
      (immediate and 6months later), to the psychiatric training course. The Control
      group was not involved in the intervention. The course was run over a 4-day
      period in June 1999. A 26-item self-administered questionnaire to assess the PHC
      physicians' attitudes was used. RESULTS: The study group consisted of 45
      trainees, 24 (53%) of whom were men. The control group, 121 out of 166
      physicians, responded to the questionnaire, with an 83% response rate, men
      forming 49%. The data analysis indicated a significant improvement in the PHC
      physicians' attitude after the course (P<0.0001). Six months later, as compared
      with their immediate post-test, the positive attitudes persisted within the study
      group (p-value=0.274). Multiple regressions indicated that the duration of
      undergraduate psychiatric training was the only contributor factor. CONCLUSION:
      This training course resulted in a positive change in the trainees' attitudes.
      Besides, it showed that the undergraduate psychiatric training had a favourable
      effect on the PHC physicians' attitude. Therefore, there should be frequent
      mental health training programs for PHC physicians. Moreover, physicians who
      spent longer period in undergraduate psychiatric training should be given the
      priority to work in PHC settings.

PMID- 23012034
TI  - Hearing impairment and hypertension among long distance bus drivers.
AB  - OBJECTIVES: To investigate the prevalence of possible hearing impairment and
      hypertension in long distance bus drivers compared to the city bus drivers in
      Abha city. METHODS: This was a cross-sectional study involving 62 long distance
      bus drivers and 46 city bus drivers from October 2001 to March 2002. A specially
      designed questionnaire was administered to the drivers to explore some of their
      socioeconomic backgrounds. A pure tone air conduction audiometry and blood
      pressure measurements were performed. RESULTS: Long distance bus drivers'
      workload is significantly higher than that of city drivers (total weekly hours
      64.0+/-14.3 compared to 46.7+/-5.5). Hearing impairment was significantly more
      among long distance drivers in the frequencies of 250, 500, 1000 and 2000 Hz
      especially in the left ear even after age corrections. The prevalence of mild
      hearing loss and hypertension were also higher among the long distance drivers
      (19.4% vs 4.5% and 38.7% vs 13% respectively). CONCLUSION AND RECOMMENDATIONS:
      This study showed more hearing affection and a higher prevalence of hypertension
      among long distance bus drivers than their counterparts operating in the city.
      Their hearing acuity should be tested before they start work and regularly
      afterwards. The stresses and strains of the job should be further studied and
      relieved; and regular health checks including blood pressure monitoring are to be
      instituted.

PMID- 23012035
TI  - A pilot study of faith healers' views on evil eye, jinn possession, and magic in
      the kingdom of saudi arabia.
AB  - BACKGROUND: Faith healers usually offer unorthodox therapies to their clients who
      present with an array of physical and psychological symptoms suggestive of the
      evil eye, jinn possession, and magic. OBJECTIVE: This exploratory pilot study
      aims to analyse the pattern of narrated symptoms and treatments given by faith
      healers practising in the Al-Qassim region, Saudi Arabia. METHOD: Forty five
      faith healers who consented to this study were given a predesigned, self
      administered, semistructured questionnaire to collect the relevant data. RESULTS:
      Notably, most faith healers have a poor repertoire of psychiatric symptoms, which
      could not specifically differentiate the three spiritual disorders. They tend to
      recommend an array of therapies rooted in religious concepts for the treatment of
      their clients who, they claim, show substantial improvement in their mental
      suffering. CONCLUSION: The revealed symptomatology of each disorder alone may not
      be specific but it certainly helps them not only to identify these disorders but
      also to prescribe unconventional therapies. Future research should look
      systematically into the diagnostic and treatment methods for these disorders.

PMID- 23012036
TI  - THE EMPEROR's CLOTHES.

PMID- 23012037
TI  - Monitoring the practice and progress of initiation of breastfeeding within half
      an hour to one hour after birth, in the labor room of king khalid university
      hospital.
AB  - PURPOSE: To monitor the progress in the practice of early breastfeeding of
      newborn babies within half an hour to one hour after delivery, and to identify
      the reasons for not breastfeeding the babies in the labor room. PATIENTS AND
      METHODS: This is a descriptive study conducted in the labor and delivery rooms of
      King Khalid University Hospital during the months(5) of Jumada I and (11)
      Dhulqada 1422H. A total of 602 women were included in the study. A structured
      form was used to assess the extent of feeding and the reasons for not
      breastfeeding in the first 1/2 to 1 hour after birth. The frequency and the
      percentage were used to compare the data. RESULTS: It was encouraging to find
      that 60% of the women breastfed their babies within 1/2 an hour to 1 hour after
      birth. Of the reasons for not breastfeeding the babies early, two were of the
      greatest concern. The first is that 13% of the women were either too tired to
      breastfeed or refused to do so at this early stage. Secondly, the majority of the
      mothers who had had cesarean sections did not breastfeed their babies.
      CONCLUSION: Mothers and their families play a very vital role in building the
      health of the nation. This can be achieved by early breastfeeding, which
      contributes to the rearing of healthy babies, increase in intelligence and the
      building of strong future generations. The health care professional must have
      continuous education and be frequently updated on breastfeeding standards.

PMID- 23012038
TI  - Academia and accountability: the importance of role modeling.

PMID- 23012039
TI  - Sociodemographic variables affecting the health seeking behaviour of mothers in a
      saudi community.
AB  - OBJECTIVES: Studies have shown that good antenatal care is associated with
      favorable outcome for both mothers and children. However, there are several
      factors that influence the utilization of such care even when available. The
      objective of this paper is to examine maternal demographic variables that
      influence antenatal care and the desire of mothers to consult a physician when
      their children aged below two are ill. METHODS: This is a cross-sectional study
      of women living in Riyadh, Saudi Arabia. From a map of residential areas, a multi
      stage sampling approach was employed to select a random sample of houses. All
      women with children aged less than two years were included in a house- to- house
      survey. A structured questionnaire was used for data collection. Epi-Info was
      used for statistical analysis. RESULTS: Results show that 96.6% of the mothers
      had at least one antenatal care visit, while 80.9% had had more than six visits.
      Delivery under medical supervision was reported by 97.8% of the sample. The use
      of antenatal care and the number of visits were statistically significantly
      associated with age, education and marital status. The last two variables were
      also statistically significantly associated with the place of delivery. Nearly
      83% of the mothers reported one or two illnesses in their children within the
      last two weeks. About 90.5% of these mothers consulted a physician on the illness
      and there was a 12.4% severe morbidity rate as evidenced by hospital admission.
      Physician consultation was statistically significantly associated with
      nationality, education and the occupation of the mother p<0.05. Hospital
      admission was also statistically significantly associated with age, nationality
      and occupation of the mother p<0.05. The commonest illness in the children in the
      last two weeks was diarrhea (34.3%) followed by fever (33.4%) and breathing
      difficulties (16%), although the highest frequency of episodes of illness was
      diarrhea and fever. Nevertheless, breathing difficulties followed closely by ear
      infection constituted the two highest prevalences among children who were brought
      for medical consultation (94.4% and 93.3% respectively). CONCLUSION: The study
      shows a higher proportion of mothers attending antenatal care than has been
      previously reported for the country. The pattern of reported children's illnesses
      reflects what has been previously seen from hospital studies. It also shows a
      high rate of physician consultation. This is probably due to the extensive
      coverage of free government health services in Riyadh. It will be worthwhile to
      document other socio-demographic variables affecting health seeking behavior of
      mothers in other parts of the country. There is a need to educate young
      illiterate mothers in sound child rearing practices. This will help minimize the
      distress of childhood diseases.

PMID- 23012040
TI  - The validity of clinical criteria in predicting pneumonia among children under
      five years of age.
AB  - BACKGROUND: Pneumonia is a major cause of morbidity and mortality, especially
      among infant and young children. Early diagnosis and treatment is essential to
      reduce the risk. To achieve this, physicians require high quality diagnostic
      indicators. The aim of the present study is to assess the validity of clinical
      symptoms and signs in predicting pneumonia among children below the age of 5
      years. PATIENTS AND METHODS: This is a case series study for a sample of 103
      children aged 4 days-59 months who were admitted to Al-Khanssa Teaching Hospital,
      Mosul, Iraq, suffering from respiratory symptoms and for whom a chest x-ray was
      requested. Sensitivity, specificity, predictive values and likelihood ratios were
      estimated for each clinical criterion. RESULTS: Pneumonia was diagnosed on
      radiological bases in about 70% of the patients. All symptoms had high
      sensitivity with very low specificity. The best positive predictive values for
      symptoms were for fast and difficult breathing. However, the signs of Crackle,
      Tachypnoea, nasal flarring and chest indrawing yielded the best sensitivity
      estimates. Moreover, a body temperature of >=38  degrees C was the best single
      predictor of pneumonia with a sensitivity of 67% and specificity of 75.8%. The
      absence of the 3 signs (nasal flaring, chest indrawing and crackles) ruled out
      pneumonia effectively. The sensitivity of this combination of signs was 98.6%.
      Detecting a body temperature >=38  degrees C and grunting simultaneously was
      adequate to confirm the disease. CONCLUSIONS: The study suggests that using
      clinical criteria in combination could improve physicians' prediction of
      pneumonia among children.

PMID- 23012041
TI  - Hypertension care in Al asyah primary health care center, Al qassim, saudi
      arabia: an audit of structure, process, and outcome.
AB  - OBJECTIVES: The objective of this study is to assess the quality of hypertension
      care in Al-Asyah primary health cares (PHC) center, Al Qassim Region, Saudi
      Arabia through an auditing of structure, process, and outcome. SUBJECTS AND
      METHODS: All files of registered hypertensive patients in the PHC center were
      reviewed as recommended by WHO, National Quality Assurance protocol, protocol of
      management of hypertension and criteria in the Sixth report of Joint National
      Committee on detection, evaluation and treatment of high blood pressure (JNCVI),
      to evaluate the structure, process, and outcome of hypertension care. RESULT: All
      hypertensive patients registered in Al Asyah PHC center ( 201 patients ) were
      included in this study. The prevalence of HTN among adults (>=15 years) was7.4%
      and increased with age. Patients were mostly Saudi (94.5%) with a mean age of
      58.6 +/- 13.9 years. Most of the patients were diagnosed as essential HTN (98.5%)
      at Al Asyah PHC center (87.1%). The mean duration of the HTN was 7.7 years, and
      48.8% had a family history of HTN and 35.3% had diabetes mellitus. Most patients
      were obese or overweight (53.7% and 31.3% respectively), blood pressure of 79.6%
      of the patients was well controlled, and 45.3% of these patients had at least one
      complication. Ischemic heart disease, left ventricular hypertrophy, stroke, and
      myocardial infarction were the most common recorded complications. CONCLUSION:
      This study proves that all essential resources needed for hypertension care are
      available, but the results of process and outcome indicators show the need for
      the improvement of the referral system as well as good continuous constant health
      education programs to encourage the patients, their families and the community to
      observe more healthy lifestyles.

PMID- 23012042
TI  - Frequency of depression among patients with acute coronary syndrome, eastern
      region, saudi arabia.
AB  - BACKGROUND: Three decades ago, Epidemiologists began to report a strong
      association between depression and cardiovascular disease - morbidity and
      mortality, and in the last decade, many large-scale studies have identified
      depression as an important risk factor for Coronary Artery Disease (CAD) and its
      morbidity and mortality. OBJECTIVES: To determine the frequency of clinical
      depression among patients admitted with Acute Coronary Syndrome (ACS) to the
      Coronary Care Unit (CCU) at King Fahd Hospital of the University (KFHU), and to
      find out if there is any relationship between depression and the traditional risk
      factors for CAD. METHODS: One hundred and two patients admitted consecutively
      with ACS completed the self-rated Beck Depression Inventory (BDI) in their native
      language. The patients were classified into two groups: Group A comprising
      patients with no symptoms of depression and patients with subclinical or
      borderline depression, scored less than 21 points on BDI score scale; and Group B
      composed of those who scored 21 points and above. Various statistical tests were
      used whenever appropriate. RESULTS: One hundred and two patients completed the
      BDI. Ninety-Two (90.2%) were males, with a mean age of 52.14+/-12.14 years. Of
      these, 37.3% were Saudis, 25.5% Non-Saudi Arabs, 31.4% from the Indian
      subcontinent and 5.9% were other Asians. Patients from the Indian Subcontinent
      were significantly younger than the Saudis (p<0.0001). The evidence of clinical
      depression was found in 20.6% of all patients, 13.2% of Saudi patients, 19.2% of
      Non-Saudi Arabs and 34.4% of those from the Indian subcontinent. There was a
      significant difference in the frequency of clinical depression between Saudi
      patients and the Indians (p=0.035). Smoking and dyslipidemia were the only strong
      predictors of clinical depression in our study. CONCLUSION: Depression is
      unquestionably associated with CAD. Its frequency in our patients with ACS was
      20.6%, and the highest frequency was recorded among patients from the Indian
      subcontinent (34.4%). Smoking and dyslipidemia were the strongest independent
      risk factors for depression.

PMID- 23012043
TI  - Bacterial contamination of stethoscopes.
AB  - BACKGROUND: A stethoscope, an essential tool of the medical profession, can
      become a source of nosocomial infection. OBJECTIVE: To determine the frequency of
      bacterial contamination of stethoscopes as well as the practices used for
      cleaning them. METHODS: Cultures were taken from 100 stethoscopes used by
      different medical personnel in different hospital services. The stethoscopes were
      collected while the staff filled in a questionnaire. RESULTS: Thirty (30%) out of
      the 100 stethoscopes surveyed were contaminated with microorganisms. The majority
      of organisms isolated were gram-positive bacteria (gram positive bacilli 12%,
      gram-negative bacteria 9%, gram-positive cocci 9%). None of the stethoscopes grew
      methicillin-resistant staphylococcus aureus. Overall, 21% of the health personnel
      cleaned their stethoscopes daily, 47% weekly, and 32% yearly. None of the health
      care workers cleaned their stethoscopes after every patient. Nurses cleaned their
      stethoscopes more often than physicians and medical students. CONCLUSION:
      Stethoscopes may be important in the spread of infectious agents. Their regular
      disinfection after use on each patient should be considered, particularly in such
      areas of the hospital, as the critical care units, and oncology units which house
      many patients with antibiotic-resistant organisms.

PMID- 23012044
TI  - Analysis of diarrhea episodes in children reported at a primary health care
      center in abha city in the year 2002.
AB  - OBJECTIVE: To determine the incidence, characteristics and the different factors
      associated with diarrhea events reported at the Primary Health Care (PHC) level
      in children under five years of age. MATERIAL AND METHODS: All reported cases of
      diarrhea in children under 5 in the primary health care (PHC) center of Wasat
      Abha, Abha city during the year 2002. The medical records of patients were
      reviewed for name, sex, date, duration of diarrhea and character of stool, type
      of feeding, degree of dehydration, the treatment received and the outcome.
      RESULTS: The overall incidence /child/year 2002 was 1.2 episodes. The total
      number of diarrhea episodes in that age group was 573 cases giving an incidence
      rate of 9.9% for the year 2002. Two thirds of the episodes of diarrhea (64.6%)
      occurred in females, and 60.9% of the episodes affected 7-12-month olds. The
      majority of diarrhea episodes (89.4%) lasted less than 7 days and only 3.7% of
      cases were moderately dehydrated. Ninety four percent of the cases improved and
      only 1.7 % were admitted to the hospital. CONCLUSION: The incidence of diarrhea
      episodes in the under fives in the year 2002 was lower than the national rate
      reported in 1993. Female children had about twice the incidence of diarrhea in
      male children and the highest incidence was observed in the 7-12-month olds. The
      majority of cases were acute. It is recommended that studies on the incidence of
      diarrhea in all PHC centers be done in order to monitor the progress of diarrhea
      in children and implement suitable preventive measures.

PMID- 23012046
TI  - Efficiency versus effectiveness of the saudi family doctor.

PMID- 23012045
TI  - Is skinfold thickness as good as DXA when measuring adiposity contributions to
      insulin resistance in adolescents?
AB  - OBJECTIVE: We compared adiposity from triceps and subscapular skinfold thickness
      (SF) with total body fat from dual energy X-ray absorptiometry (DXA) in their
      associations with HOMA insulin resistance for a large sample of US adolescents.
      METHODS: We analyzed cross-sectional data from 1496 adolescents, ages 12.0-17.99
      year examined as part of the US national health and nutrition examination survey
      (NHANES) cycles 2001-04. Data collected included skinfold thicknesses, DXA-based
      total body fat (DXF), serum insulin and fasting glucose for homeostasis model
      assessment of insulin resistance (HOMA-IR). Regression models adjusting for
      complex survey design effects and correspondence analyses were used to study
      associations with HOMA-IR and concordance between the two measures of adiposity.
      RESULTS: SF and DXA models had identical precisions for estimating continuous
      HOMA-IR, based on bootstrap estimations. For boys, RMSEs = 0.53 (95% CI: 0.49
      0.58) and 0.53 (95% CI: 0.48-0.57) for SF and DXA models respectively; and for
      girls RMSEs were SF = 0.45 (95% CI: 0.41-0.48) and DXA = 0.46 (95% CI: 0.42
      0.48). Both adiposity models identified high proportions of the same individuals
      (positive percent agreement: 80-81%) with exact agreements exceeding 92% for
      identifying adolescents at elevated risk of IR in both sexes. CONCLUSIONS:
      Triceps and subscapular skinfold thicknesses estimate HOMA-IR and identify those
      at highest risk for insulin resistance as well as total body fat from DXA.
      Skinfold thickness provides an inexpensive and widely applicable measure of
      fatness that is appropriate for studies of insulin resistance and perhaps other
      metabolic variables in adolescents.

PMID- 23012047
TI  - Why a journal section on medical education?

PMID- 23012048
TI  - The public health burden of physical inactivity in saudi arabia.
AB  - Because of the enormous changes in the lifestyle of Saudis in the last three
      decades, the risk factors of coronary heart disease (CHD), including physical
      inactivity, are increasingly becoming prevalent in the society. This paper
      provides an overview of the importance of physical activity in health promotion
      and disease prevention, and discusses the public health burden of physical
      inactivity in Saudi Arabia. Available evidence clearly indicates that physical
      inactivity is extremely prevalent in the different ages and sex of the Saudi
      population. This high prevalence of inactivity in Saudi society presents a major
      public health burden, as evidenced by the high risk in the Saudi population as a
      risk of physical inactivity compared with the populations of United States and
      the United Kingdom. Unless concrete steps are taken to reduce physical inactivity
      in the Saudi population, the future public health cost would be enormous. It is
      well known that physical activity is associated with numerous health benefits and
      plays a major role in modifying many other CHD risk factors. Finally, several
      recommendations for reducing physical inactivity and promoting active life in the
      Saudi population have been discussed.

PMID- 23012049
TI  - Frequency of risk factors for coronary heart disease among diabetic patients in
      Al-rabwah phc center in riyadh.
AB  - BACKGROUND: Diabetes mellitus associated with high prevalence and incidence of
      CHD is a common problem in Saudi Arabia. OBJECTIVES: To assess the percentage of
      major modifiable risk factors for CHD among diabetic patients. METHODS: This is a
      retrospective study conducted on 495 diabetic patients (292 males and 203
      females) attending the Miniclinic at Al-Rabwah PHC center in Riyadh. Their
      records for the months of April and May 2001 were reviewed. Data collected from
      the patient's files included body mass index (BMI), blood pressure, total
      cholesterol, triglyceride, and smoking status. In addition, information on the
      duration of diabetes was obtained and fasting blood sugar was done. RESULTS: The
      percentage of overweight males was 43.2% as against 22% females, the figure for
      males being highly significant (p<0.0001). Obesity which was 27.9% in males and
      64.1% in females, was highly significant in females (p<0.0001). For cholesterol
      (>= 5.2 mmol/l) was 49.5% in males versus 68.5% in females (p=0.0036). High
      triglyceride (>= 1.7%) was 50% in both genders. 13.4% of males were hypertensive
      as against 44.3% female hypertensives which was highly significant in females
      (p<0.0001). 19.5% of the males smoked. There was no significant difference
      between risk factors for CHD and duration of diabetes except that there were more
      smokers among those who had had diabetes for less than 10 years. Most of the
      diabetics with poor glycemic control (FBS> 8.3mmol/l) tended to be smokers, were
      more obese, had high triglyceride and high total cholesterol. CONCLUSION: The
      findings indicated that diabetic patients have high percentage of risk factors
      for CHD and more females than males are at risk. Therefore, early intervention is
      required if the incidence of CHD among diabetic patients is to be reduced.

PMID- 23012050
TI  - Pattern of childhood poisoning in abha city - southwestern saudi arabia.
AB  - OBJECTIVE: To describe the pattern of childhood poisoning in the Emergency Room
      (ER) of the Pediatrics Department in Aseer Central Hospital (ACH), in order to
      suggest possible causes and preventive measures. METHODS: This is a retrospective
      study of cases of childhood poisoning or ingestions attending the pediatric
      emergency room of Aseer Central Hospital or those admitted to the Pediatric
      Department of same hospital in Abha, Kingdom of Saudi Arabia, during the period
      of January 2000 to December 2003. Children aged 12 years and below were included.
      Review of records was done to collect data on clinical information such as age,
      sex, type of poison, clinical condition on admission as well as the time, place
      and date of exposure to the offending agent. RESULTS: In this study, 114 poisoned
      children aged 12 years and below were studied. It was found that children from 2
      4 years were more liable to poisoning (81%, p<0.001). Males were (68%) while
      females were (32%), with a sex ratio of 2.2:1. Medical drugs offended the most
      (72%, p<0.001). As regards clinical condition on admission, drowsiness, nausea
      and vomiting as well as abdominal pain represented (82%) of the cases. Daytime
      was when 80% of poisoned cases were admitted (p<0.001). The peak months were from
      June to August (71%, p<0.01). As regard the place of exposure to offending agent,
      living rooms and bedrooms accounted for 58% of the cases(p<001). CONCLUSION: The
      peak age for poisonings in children is before the age of four with significantly
      high diurnal frequency, significant seasonal variation in favor of summer.
      Medical drugs were the most common agents of poisoning, and living rooms and
      bedrooms the places where most poisoning occurred. Good and continuous
      supervision by parents is essential, especially from the age 1-5 years. There
      should also be legislation for the use of child resistant containers for home
      medicines and household agents.

PMID- 23012051
TI  - Perception and satisfaction of secondary school students with the dermatological
      services in riyadh city.
AB  - BACKGROUND: Health care that meets patient's expectations inevitably leads to a
      high level of patient satisfaction and in turn to an improved compliance of the
      patient with the prescribed management. Accordingly, health care services are
      more likely to improve. Numerous factors have been associated with patient
      satisfaction and studies have been done to investigate this relationship.
      However, not much work has been done in the field of dermatological service.
      OBJECTIVE: This study was designed to investigate the experience, satisfaction
      and expectations of adolescents of the dermatological services provided in the
      outpatient ambulatory facilities. METHODS: A cross-sectional study was conducted
      on 700 male and female secondary school students in Riyadh in Saudi Arabia. A
      self-administered questionnaire was used to collect data from the students. Data
      were related to the perception, expectation and satisfaction of a specific group
      of students. The overall and different items of satisfaction with the
      dermatological service including satisfaction with the physician providing the
      service, and satisfaction with the setting of the care were estimated. RESULTS:
      The age range was 15-29 years with a mean of 18.1 +/- 1.8 years. Of the 517 (74%)
      respondents, 267 (51.6%) males and 250 (48.4%) females, 457 (88.4%) were Saudis.
      With regard to expectation and preference, 385 (73.9%) would like to have
      dermatologists at each PHC center; 310 (59.5%) preferred a government setting for
      treatment. Statistically significant gender preference was observed (p<0.001);
      males preferred male dermatologist and females preferred female dermatologist,
      142 (52.8 %) and 167 (66.5%), respectively. Only 14 (2.7 %) had no preference. As
      far as the experience with dermatological service was concerned, 273 (52.4%) had
      had one or more consultations, 225 (82.4%) had used the services for curative
      purpose, 91 (33.3%), 104 (38.1%) and 78 (28.6%) had used governmental, private
      and both facilities, respectively. Overall, 188 (68.9%) patients were satisfied,
      but of those who had availed themselves of the government services, 36 (42.3%)
      were not satisfied and 68 (24.9%) considered the waiting time too long.
      CONCLUSION: Dermatological services at the governmental facilities do not meet
      the expectations of the adolescent. Well-designed operational research studies on
      the appropriate sample, focusing on patients' expectation and satisfaction with
      appropriate sample is required. Such studies will facilitate the work of the
      policy makers and service implementers and help them to develop appropriate human
      and other resources in order to tailor dermatologic services to the clients'
      expectations.

PMID- 23012052
TI  - Acute abdomen with pneumoperitoneum.
AB  - Acute appendicitis is a common cause of acute abdomen. However, it is a rare
      cause of pneumoperitonium. In this report the surgical diagnoses and management
      will be discussed in detail.

PMID- 23012053
TI  - Teaching tips - questioning.

PMID- 23012054
TI  - Feasibility and acceptability of objective structured clinical examination (osce)
      for a large number of candidates: experience at a university hospital.
AB  - OBJECTIVE: To assess the feasibility and acceptability of using objective
      structured clinical examination (OSCE) for a large number of medical students.
      METHODS: All medical students (291) who had completed the basic surgical course
      were examined by objective structured clinical examination (OSCE) at the College
      of Medicine, Riyadh, for the first time. A 5-scale questionnaire was filled by
      the examiners at the end of the examination each day. Another questionnaire was
      filled by the students as a feedback. RESULTS: All students agreed that the
      organizational aspect of the examinations was smooth and the time for each
      station was adequate. 86% of the students agreed that the stations were within
      the content of the course, 82% agreed that the examination was fair and objective
      and 93% wanted this method to be followed in the assessment of third year medical
      students, instead of the traditional examination (written and single long case).
      Similar responses were received from the examiners who were involved in the
      exams. CONCLUSION: OSCE is a practical and acceptable method for assessing
      medical students' basic surgical skills, even for a large number of candidates,
      if facilities are available in the examination center. Replacing written exams
      with OSCE depends on the design of stations to test knowledge adequately in scope
      and depth probably at problem solving level.

PMID- 23012055
TI  - Motivation to learn physiology using end of lecture quizzes.
AB  - OBJECTIVES: Exams are known to be strong external motivators for study. In this
      study, this observation was utilized to increase the attendance and attention of
      students in lectures. METHODOLOGY: Tests were conducted at the end of every
      lecture, on the material covered in that lecture. A total of 12 tests on renal
      physiology, consisting of 4 MCQs each, were done. Students (137 male & female)
      were requested to fill a questionnaire of 18 items, rated on a 5-point scale in
      addition to some open questions. RESULTS: Analysis of the 137 questionnaires
      showed that students who had participated had found it enjoyable. However, some
      students pointed out certain disadvantages in the practice. CONCLUSION: It is
      concluded that end-of- lecture quizzes are an extremely useful stimulus for
      motivation provided they are random, answers are given, and cheating is
      minimized.

PMID- 23012056
TI  - About patients and doctors.

PMID- 23012057
TI  - Audit of structure, process, and outcome of diabetic care at Al asyah primary
      health care centre, qassim region, saudi arabia.
AB  - OBJECTIVE: To assess the quality of diabetic care in Al-Asyah primary health care
      (PHC) center, Qassim region, KSA , through an auditing of structure, process, and
      outcome. METHODOLOGY: The files of all registered diabetic patients in this PHC
      center were reviewed. The indicators for structure were evaluated according to
      the National Quality Assurance protocol and manual of chronic diseases, and those
      for process were assessed by a modified scoring system. The outcome indicators
      were evaluated using the recommendations of American Diabetic Association (ADA)
      2002. RESULT: Dietician, diabetic educator and Hb A1C, HDL level, LDL level were
      the most common non available resources. Out of 4628 patients registered in this
      PHC center, only 159 patients had diabetes. The prevalence of diabetes among
      registered adults aged 15 years and above was 5.8% and this increased with age.
      The patients were mostly Saudi (96.2%) and married (75.5%). They included 83
      females (52.2%). The mean age was 56 years. Most of the patients were Type 2
      (95.6%) and most were diagnosed at the PHC center (94.3%). The mean duration of
      the diabetes since diagnosis was 6.4 years. All checked process items showed high
      percentages of coverage (73% and above) except for the examination of the fundus,
      and the measurement of the triglyceride levels. Results showed that most of the
      samples were obese or overweight (49.7% and 32.7% respectively). While 21.4% had
      good diabetic control, 42.8% had poor diabetic control. Patient compliance to
      appointment was good (98.1%), and 13% of the diabetic patients had at least one
      reported complication. CONCLUSION: This study proves that some essential
      resources needed for diabetic care were inadequate. Provision of these resources
      is essential for the improvement of the quality of health care for diabetic
      patients. Also, there is a need to improve the referral system and establish an
      appropriate health education program to encourage patients, their families and
      the community to follow a more healthy life-style.

PMID- 23012059
TI  - Detection of hepatitis C virus core antigen in blood donors using a new enzyme
      immunoassay.
AB  - OBJECTIVES: The purpose of the study was to evaluate the presence of hepatitis C
      virus [HCV] core antigen (HCV core Ag) in blood donors at King Fahd Hospital of
      the University, Al-Khobar, using the new HCV core Ag assay, and to correlate this
      finding with anti-HCV antibodies detected in the same samples using the standard
      Abbott MEIA(microparticle enzyme immunoassay). MATERIALS AND METHODS: A total of
      898 samples from blood donors were analyzed using the new assay prototype
      designed to detect and quantify total HCV core Ag in serum (Ortho-Clinical
      Diagnostics). Positive results were confirmed by the neutralization assay. The
      results of the HCV core Ag assay were compared with the results of the standard
      Abbott MIEA which measures anti-HCV antibody. RESULTS AND CONCLUSIONS: Out of the
      898 samples tested, 18 samples were found to be positive by the HCV core Ag assay
      (2%). Out of these, 3 samples were confirmed positive by the neutralization
      protocol (0.33%). All the HCV core Ag positive samples were negative for anti-HCV
      antibodies (using MEIA by Abbott). These 3 donors may have been in the window
      period of HCV infection, or may be low responders for the HCV antigens, and are
      thus unable to mount detectable antibody level. The HCV core Ag assay is a
      potentially useful assay for screening blood donors, which will minimize the risk
      of using HCV positive blood from a patient in the window period of HCV infection.

PMID- 23012058
TI  - The value of screening tests for detection of prostate cancer in 1000 saudi men.
AB  - OBJECTIVES: Predicting the value of screening tests in the detection of prostate
      cancer in Saudi men. METHODS: The study was conducted in King Fahd Hospital of
      the University, Al-Khobar. Total, free and percent free serum prostate specific
      antigen (PSA) were measured in Saudi men above the age of 45 years. Transrectal
      ultrasonography (TRUS) and needle biopsy were performed on those with suspicious
      digital rectal examination (DRE) and or PSA >4ng/ml. A group of 849 Saudi men
      were with normal PSA levels and normal DRE were considered cancer free.. The
      remaining 151 patients with PSA >4ng/ml were suspicious for prostate cancer. Only
      55 patients agreed to have TRUS and needle biopsy RESULTS: PSA testing and DRE
      had the highest positive predictive value but this value dropped when TRUS was
      added. CONCLUSION: PSA and DRE are the main tests for the detection of prostate
      cancer, while TRUS is valuable when sample are taken of a wide area of prostate
      tissue in men at high risk of cancer.

PMID- 23012060
TI  - Pattern of pulmonary manifestations in patients with sickle cell disease and
      Fever.
AB  - OBJECTIVES: The objective of this study was to determine the frequency and
      pattern of pulmonary manifestations in febrile patients with sickle-cell disease
      (SCD), a condition prevalent in the Eastern Province of Saudi Arabia. DESIGN: The
      main pulmonary complications in febrile adult SCD patients were studied between
      January 1986 and December 1990. MATERIAL AND METHODS: The medical records, chest
      X-rays and microbiological data of all febrile (temperature >38 degrees C) SCD
      patients >12 years of age admitted to KFHU during the study period were
      retrospectively reviewed. RESULTS: Of the 164 patient-episodes in 49 male and 19
      female SCD patients, chest X-rays were abnormal in 33 (20.1%) episodes. Of these
      33, there was consolidation in 17 (52%), pleural effusion in 6 (18%), pleural
      effusion and consolidation in 4 (12%), consolidation with collapse in 3 (9%),
      pleural thickening in 2 (6%) and bronchogenic carcinoma in one. CONCLUSION:
      Pneumonia was the most common complication in Saudi SCD patients with abnormal
      chest X-rays. Chest X-rays are most useful in SCD patients with symptoms of chest
      infection, abnormal chest signs, or those with persistent fever during vaso
      occlusive crisis.

PMID- 23012061
TI  - Thyroid storm presenting as acute abdomen and normothermia.
AB  - Thyroid storm is a known complication of thyroid surgery. Nowadays, it is
      commonly seen in thyrotoxic patients. In this case report we discuss a patient
      who presented with acute abdomen and normothermia and was discovered to have
      thyrotoxicosis, a rare feature of thyroid storm.

PMID- 23012062
TI  - Teaching tips - 10 factors in media selection.

PMID- 23012063
TI  - Community-based family medicine course: does it have impact on students' learning
      achievements, attitude and career choice?
AB  - OBJECTIVE: To assess the impact of a six-week Family Medicine (FM) course on
      students' self-assessment of their own knowledge, skills and their attitude
      towards innovative learning methods and career choice before and after the
      course, and their evaluation of different aspects of the course curriculum.
      DESIGN: An observational study, where the study subjects were requested to fill
      out a standardized five-point Likert scale questionnaire at the start and at the
      end of the course. The questionnaire explored their knowledge and attitude in
      addition to their general evaluation of the course. One hundred forty-seven
      fourth year medical students who undertook FM clinical rotation were the study
      subjects. The course had some innovative features. For example, students were
      involved in the selection of the course content by identifying their learning
      needs. RESULTS: A comparison of pre and post-test observations showed a
      statistically significant improvement in students' assessment of their knowledge
      (p < 0.0001) and clinical skills (p = 0.012). A significant positive change was
      also observed in their choice of FM as a future career (p = 0.008). The
      intervention was not effective (non-significant difference) on (i) students'
      attitude towards innovative learning methods (p = 0.314) and (ii) students'
      attitude towards patients and certain ethical issues (p = 0.99). As the
      curriculum stemmed from collaboration of learners and teachers, the students were
      satisfied with the content. RECOMMENDATIONS: There is a need to improve the
      training in the HC by recruiting family practitioners (FP) who have had residency
      training for the specialty and to train the other physicians in how to supervise
      and guide medical students. Topics on ethical issues should be introduced into
      the college curriculum.

PMID- 23012065
TI  - Asthma awareness month.

PMID- 23012064
TI  - Preparation of high-performance water-soluble quantum dots for biorecognition
      through fluorescence resonance energy transfer.
AB  - An improved method for the synthesis of high-performance and water-soluble
      quantum dots (QDs) involving the encapsulation of mercaptosuccinic acid coated
      QDs (MSA-QDs) with poly(diallyldimethylammonium chloride) (PDDA) followed by
      their direct photoactivation with fluorescent radiation near 295 K to yield PDDA
      coated QDs (PDDA-QDs) has been demonstrated. The quantum yield (QY) of the PDDA
      QDs was significantly improved from 0.6 (QY of MSA-QDs) to 48%. By using this
      synthetic strategy, highly photoluminescent PDDA-QDs of varied size were readily
      prepared. The surface properties of PDDA-QDs and MSA-QDs were extensively
      characterized. The highly luminescent and positively charged PDDA-QDs serve as a
      useful and convenient tool for protein adsorption. With a Delta(5)-3-ketosteroid
      isomerase adsorbed PDDA-QD complex, the biorecognition of steroids was
      demonstrated through the application of fluorescent resonance energy transfer.

PMID- 23012066
TI  - How to approach the problem of low back pain: an overview.
AB  - The management of patients with low back pain (LBP) problems by primary care
      physicians or even spine specialists differ significantly and little is known
      about treatment strategy.This review is to present the clinical profile and to
      assess the most common treatment modalities of patients with low-back pain in
      order to improve the clinical judgment of the treating physician.Data were
      obtained from a midline literature search of articles in English. A manual
      revision of original articles was done and demonstrative figures from patients at
      our institute were added.LBP is an extremely common problem. It is characterized
      by attacks, remissions and exacerbations. It is best managed by a
      multidisciplinary team. Primary coordination of treatment may depend on the
      patient's need and the awareness of the treating physician of the importance of
      history and physical examinations. The following suggested protocol may help to
      identify red flags that denote more serious conditions.

PMID- 23012067
TI  - Predictors of short-term hospital readmissions of asthmatic children.
AB  - BACKGROUND: The admission rate for bronchial asthma has increased dramatically
      all over the world. Part of this increase in hospital admissions is due to
      patient readmission. OBJECTIVE: To determine the risk factors associated with
      short-term hospital readmission of pediatric patients with asthma within two
      months of the last hospital admission. METHODS AND SETTING: A retrospective case
      control study using the registration books of both admissions and discharges to
      identify patient groups. All hospital records of patients admitted from August
      1998 through December 2002 at Aseer Central Hospital, southwestern Saudi Arabia
      were reviewed. Patients who were admitted during this period of study and
      readmitted to hospital within two months were used as the study group (n=28) and
      those patients admitted within the same period but not readmitted within two
      months constituted the control group (n=45). Demographic variables, route of
      admission, patient's previous medical history, clinical assessment, hospital
      treatment as well as discharge treatment were obtained and entered for analysis.
      RESULTS: Twenty-eight patients were readmitted within two months of their
      discharge from hospital (17 boys and 11 girls). Seventy percent of these were
      less than four years of age. Significant predictors of readmission were: prior
      history of asthma admission (adjusted OR 2.21,95% CI 1.08-9.10), neonatal
      intensive care graduate (adjusted OR 4.44,95% CI 1.67-9.34), bronchopulmonary
      dysplasia (adjusted OR 3.06,95% CI 2.01-7.95), recurrent aspiration (adjusted OR
      1.96,95% CI 1.08-4.27), duration of asthma symptoms more than five days (adjusted
      OR 0.15,95% CI 0.03-0.42), moderate to severe clinical assessment (adjusted OR
      1.12,95% CI 1.01-2.94), positive X-ray findings (adjusted OR 0.04,95%CI 0.011
      0.230), intensive care admission (adjusted OR 1.96,95%CI 1.08-4.63), mechanical
      ventilation (adjusted OR 0.010,95%CI 0.002-0.130), intravenous steroids (adjusted
      OR 0.104 ,95%CI 0.016-0.321). CONCLUSION: Prior neonatal intensive care unit
      admission, bronchopulmonary dysplasia, history of previous asthma admissions,
      recurrent aspirations, intensive care unit admission, intravenous steroids,
      positive X-ray findings and mechanical ventilation were significant predictors of
      asthma short-term hospital readmissions.

PMID- 23012068
TI  - Self-reported knowledge and pattern of physical activity among male school
      students and their teachers in Al khobar, saudi arabia.
AB  - OBJECTIVE: The aim of this study was to determine self-reported knowledge and
      practice of physical activity among male school students and their teachers in Al
      Khobar, Saudi Arabia. METHODS: This was a cross-sectional study conducted in the
      Al Khobar area, Eastern Province of Saudi Arabia. The target population consisted
      of third grade intermediate and all three grades of male secondary school
      students. A multistage stratified self-weighting sampling design was adopted. All
      students, a total of 1240, in the selected classes as well as their teachers
      (142) in the selected schools were included in the sample. Two sets of self
      administered questionnaires were used: one for male students and the other for
      teachers. The questionnaire contained demographic data and data on knowledge and
      practice of physical activity. RESULTS: The majority of male students knew that
      physical activity was protective against diseases in general ((92.8%) and was
      helpful in the prevention of obesity (74.4%). Teachers had significantly better
      knowledge about the benefits of physical activity. Both students and teachers had
      poor knowledge about the role of physical activity in the prevention of diabetes
      mellitus and hypertension (36.6% and 28.8% for students vs. 43.0% and 46.5% for
      teachers respectively). The frequency and duration of practice of effective
      physical activity were significantly better than their teachers (45.6% and 71.3%
      for students vs. 23.1% and 36.6% for teachers respectively). Age and the
      knowledge that exercise protects from obesity were the main determinants of
      practice of physical activity among male students. Youthfulness was statistically
      significantly associated with practice of physical activity. CONCLUSIONS:
      Teachers had significantly better knowledge about the benefits of physical
      activity than their students. Both students and teachers had poor knowledge about
      the role of physical activity in the prevention of diabetes mellitus and
      hypertension. Health education should concentrate on clarifying this area.
      Students practiced effective physical activity significantly more than their
      teachers. Programs to increase regular physical activity were suggested.

PMID- 23012069
TI  - The pattern of commoner health problems among basic school children, gezira
      state, Sudan.
AB  - BACKGROUND: The lack of baseline information on the magnitude of health problems
      among school children is considered one of the factors of the unsatisfactory
      status of school health in Sudan. Availability of such data from schools will
      help in the health promotion of school children. OBJECTIVE: To determine the
      proportions of the commoner diseases or health problems among Wad Medani basic
      school children (males and females) at the end of the school year 2000-2001.
      METHOD: This is a cross-sectional study conducted on 3862 basic school children
      (males and females).They were selected by multi-stage stratified proportional
      random sampling according to their sex and localities. A pre-designed pre-tested
      questionnaire was used to collect data which were then tabulated and
      statistically analyzed. RESULTS: The study revealed that 77.9% of the study group
      had malaria, 33% of them had sore throat, 26.4% suffered from psychosocial
      problems that affected their school performance. Dental carries 24.5%, diarrhea
      attacks 17.5%, oxyuris worm 16.8%, pneumonia 11.5, measles infection 12.4%,
      asthma 9.2% and visual defects 8.9%. Some of these problems were related to the
      poor quality of school environment including sanitation and poor nutritional
      services. These findings should be considered in planning school health
      programmes. Appropriate interventions to reduce these problems through improving
      school environment and raising the awareness of the school community towards such
      problems is recommended.

PMID- 23012070
TI  - Characteristics of immunization providers in riyadh and their self-perception of
      competency.
AB  - OBJECTIVE: To study the demographic characteristics of immunization providers in
      Riyadh City and their self-perception of competency. METHODS: A cross-sectional
      study was conducted among immunization providers in Riyadh City from August 2003
      to March 2004. This study covered 71 institutions: (25 primary health care
      centers, 30 private clinics and dispensaries, 8 government hospitals and 8
      private hospitals). Immunization providers were selected by stratified random
      process. One hundred and one physicians participated in the study and the data
      were obtained by self-administered questionnaires, tabulated and analyzed using
      appropriate statistics. RESULTS: The participating physicians were mostly
      pediatricians (50.5%) and general practitioners (38.6%). About 47% of them had
      had no training in immunization during the preceding 10 years. Self-evaluation
      revealed that 30.7% of them ranked themselves as excellent, 67.3% as average and
      2.0% as poor immunization providers. Self-confidence was associated with
      specialty, qualification, place of work, years of experience and training on
      immunization (p<0.05). Most of participating doctors (83.7%) used books as their
      references. The doctors were least confident in vaccinating pregnant and
      lactating women and the vaccination of travelers to endemic areas. CONCLUSION: To
      improve immunization services, doctors should be trained before being involved in
      this practice. There should be frequent distribution of national and
      international protocols with the auditing of the practice to improve and sustain
      a highly effective service.

PMID- 23012071
TI  - Diabetes knowledge among self reported diabetic female teachers: Al-khobar, saudi
      arabia.
AB  - OBJECTIVE: The objective of this study was to determine the general knowledge of
      diabetes among female diabetic school teachers in Al-Khobar, Eastern Province of
      Saudi Arabia. METHODS: A total of 91 female diabetic school teachers were
      interviewed in the School Health Clinic in Al-Khobar using a structured
      questionnaire. Their weight and height were measured and BMI was calculated.
      RESULTS: The results showed that understanding of diabetes was inadequate.
      Knowledge about symptoms of hypoglycemia was low. One-fourth (25%) of the sample
      of this study was using certain herbs for the treatment or management of diabetes
      mellitus. About three- fourths were overweight and obese. The results showed a
      deficiency of knowledge on the general aspects of diabetes mellitus. An
      appropriate educational material was prepared in the form leaflets, lectures and
      workshops. CONCLUSION: This paper concludes that awareness and education about
      diabetes are needed urgently among the studied sample.

PMID- 23012072
TI  - Physicians', nurses' and patients' perception with hospital medical records at a
      military hospital in riyadh, saudi arabia.
AB  - BACKGROUND: A medical record contains data on patients to support current and
      continuing patient care. Medical Records Department has the traditional role of
      keeping the patient's records safe. This is the first attempt in the Kingdom, to
      the best of our knowledge, to assess the feasibility of introducing electronic
      medical records. OBJECTIVE: The aim of the study was to assess the views of
      physicians, patients and nurses of medical records services and physicians' views
      on the use of electronic medical records. METHODS: The study was conducted with
      physicians, nurses and patients selected randomly from the Military hospital in
      Riyadh. The data was collected via a self- administered, pilot-tested, internally
      consistent questionnaire. RESULTS: On the staff of medical records, the highest
      mean score was obtained for confidentiality (2.92), and the lowest for the
      training of medical staff (1.88). On medical record documents, the highest mean
      score was reported for "information is confidentially maintained" (2.70), and the
      lowest for the organization of files within file sections (2.28). On the Medical
      Records Department, the highest mean score was reported for overstaffing (2.89),
      and the lowest for receptiveness of receptionists (2.27). Physicians had low
      scores for computer literacy, ranging from 1% for prior computer experience to
      27% for owning a computer. Physicians were not enthusiastic about the change to
      electronic medical records. CONCLUSIONS: Despite the observed shortcomings of the
      existing medical records system, it is not expected that medical records would be
      computerized in the near future since physicians have not accepted this
      technology wholeheartedly.

PMID- 23012074
TI  - Teaching tips - general questions to consider.

PMID- 23012073
TI  - Upstream investment in health care: national and regional perspectives.
AB  - Since the burden of disease has shifted towards non-communicable diseases and
      public health management, there is a greater need to direct resources to address
      risk factors of the diseases rather than the diseases themselves. The downstream
      agenda focused on treatment services and is still an important problem at the
      level of national health management. Much has been accomplished in preventive
      programs for infectious diseases in Saudi Arabia but a great deal more is needed
      to combat non-communicable diseases. While a national non-communicable diseases
      program is being established in the Kingdom, more advanced pilot projects of NCD
      can be started in the regions. A model for cardiovascular diseases in Qassim will
      be presented.

PMID- 23012076
TI  - Under fives clinic.

PMID- 23012075
TI  - The reaction coordinate of a bacterial GH47 alpha-mannosidase: a combined quantum
      mechanical and structural approach.
AB  - Mannosides in the southern hemisphere: Conformational analysis of enzymatic
      mannoside hydrolysis informs strategies for enzyme inhibition and inspires
      solutions to mannoside synthesis. Atomic resolution structures along the reaction
      coordinate of an inverting alpha-mannosidase show how the enzyme distorts the
      substrate and transition state. QM/MM calculations reveal how the free energy
      landscape of isolated alpha-D-mannose is molded on enzyme to only allow one
      conformationally accessible reaction coordinate.

PMID- 23012077
TI  - The role of psychologists in health care delivery.
AB  - Advances in the biomedical and the behavioral sciences have paved the way for the
      integration of medical practice towards the biopsychosocial approach. Therefore,
      dealing with health and illness overtakes looking for the presence or absence of
      the disease and infirmity (the biomedical paradigm) to the biopsychosocial
      paradigm in which health means a state of complete physical, psychological and
      social well-being. Psychology as a behavioral health discipline is the key to the
      biopsychosocial practice, and plays a major role in understanding the concept of
      health and illness. The clinical role of psychologists as health providers is
      diverse with the varying areas of care giving (primary, secondary and tertiary
      care) and a variety of subspecialties. Overall, psychologists assess, diagnose,
      and treat the psychological problems and the behavioral dysfunctions resulting
      from, or related to physical and mental health. In addition, they play a major
      role in the promotion of healthy behavior, preventing diseases and improving
      patients' quality of life. They perform their clinical roles according to
      rigorous ethical principles and code of conduct. This article describes and
      discusses the significant role of clinical health psychology in the provision of
      health care, following a biopsychosocial perspective of health and illness.
      Professional and educational issues have also been discussed.

PMID- 23012078
TI  - Prevention of breast cancer.
AB  - The best therapy for cancer is prevention. Primary prevention involves health
      promotion and risk reduction in the general population so that invasive cancers
      do not develop. These primary preventive measures include the cessation of
      smoking, lifestyle and diet modification, vitamins and micronutrients
      supplementation. Identification of genetic risk, understanding of carcinogenesis,
      development of effective screening tools, avoiding risk factors and effective
      chemoprevention can lead to decreased morbidity and mortality of cancers in
      general and more importantly breast cancer. Secondary prevention is the
      identification and treatment of premalignant or subclinical cancers. Screening by
      means of mammography is a typical example of secondary prevention. Tertiary
      prevention is defined as symptoms control and rehabilitation. These definitions
      may become less useful in the future as they do not account for the new incoming
      data such as molecular data.

PMID- 23012079
TI  - Health education resources availability for diabetes and hypertension at primary
      care settings, aseer region, saudi arabia.
AB  - OBJECTIVE: The aim of this study was to evaluate the availability of health
      materials and means on diabetes and hypertension at PHCCs in Aseer region, Saudi
      Arabia. MATERIALS AND METHODS: This study was carried out in PHCCs in Aseer
      region. A questionnaire was distributed to all PHCCs in the region. The
      questionnaire elicited information on the total population served, the number of
      diabetic and hypertensive patients, and the availability of health materials for
      diabetes and hypertension. Data were entered and analyzed by using SPSS. RESULTS:
      A total of 242 PHCCs out of 245 responded to this questionnaire. There were 20
      health educators (8%).Availability of health education materials ranged between
      10 to 50%. Health education programs for Diabetes and hypertension were available
      in more than 90% of PHCCs. CONCLUSION: This study revealed that most of PHCCs in
      Aseer region lacked essential health education materials and means for diabetes
      and hypertension and, therefore were in urgent need of these materials from the
      Health Education Department, private health sectors and drug companies.

PMID- 23012080
TI  - A review of predonation blood donor deferrals in a university hospital.
AB  - OBJECTIVES: To study the main causes of predonation deferral of potentially
      healthy prospective blood donors in a University Hospital Blood Bank unit, and to
      make recommendations accordingly. METHODS: A retrospective review of the main
      causes of predonation deferral of blood donors in King Fahd Hospital of the
      University (KFHU) Al-Khobar, was carried out. Records of all predonation
      deferrals from 1(st) January 1996 to 31(st) December 2003 were reviewed and
      analyzed. RESULTS: A total of 33,900 potential blood donors came to donate blood
      during the study period. A total of 6508 donors (19.2%) were deferred for various
      reasons. Analysis of the causes of deferral showed the following as the most
      common reasons in rank order: (1) recent ingestion or taking of counter
      indicative medications; (2) low hematocrit level; (3) underweight; (4) abnormally
      high pulse rate; (5) low blood pressure; (6) temperature above 37.5 degrees C;
      (7) High blood pressure; (8) presenting for donation too soon i.e. less than 8
      weeks after the previous one; (9) age below or above the accepted limit; (10) a
      previous serological positive result; (11) general appearance; (12) abnormally
      low pulse rate. CONCLUSION AND RECOMMENDATIONS: It is important to provide donors
      with a clear message on their deferral status. Increased public education about
      blood donation and the common causes of donor deferral may lower deferral rates
      and prevent a negative impact on the donor himself as well as on subsequent blood
      donations. Public education is needed also to help recruit as many volunteer
      donors as possible.

PMID- 23012081
TI  - From home to hospital: beliefs and practices related to severe malaria in Sudan.
AB  - PURPOSE: To develop effective measures of reducing the proportion of severe
      malaria presentation and deaths attributed to malaria, an adequate understanding
      of beliefs and practices in households and at the level of primary health care is
      necessary. The objectives of this paper are to explore beliefs and practices
      related to the management of severe malaria, and to identify barriers to early
      consultation. SUBJECTS AND METHODS: A cross-sectional hospital-based study was
      conducted in five hospitals in Sudan in 2003. All malaria cases admitted, or
      their care givers were interviewed by a medical doctor using pre-coded and pre
      tested questionnaire. RESULTS: Enrolled in this study, were a total of 482
      patients, 62.9% of whom were female. Almost 75.0% of the respondents perceived
      that malaria had serious complications. Anaemia as a complication was mentioned
      by 115 (32.0%) respondents. A total of 418 (86.7%) patients sought advice from
      health personnel. Of these, 305 (73.0%) did so more than 24 hours after the onset
      of the illness. Distance, lack of money, unavailability of transportation or all
      were the reasons mentioned as barriers to seeking care at hospitals. More than
      70.0% of the patients received anti-malarial drugs before admission with a clear
      preference for the injectable form of chloroquine. Multivariate analysis revealed
      that "cost of services" and "not seeking help from health personnel" were the
      determinants for late consultation. CONCLUSION: The study revealed that late
      consultation was a feature in many parts of Sudan. Among the barriers mentioned
      by the respondents, the cost of services was of the greatest concern.

PMID- 23012082
TI  - Giant juvenile fibroadenoma: experience from a university hospital.
AB  - OBJECTIVE: Fibroadenoma is one of the commonest benign breast lesions in our
      outpatient clinics. Giant Juvenile fibroadenoma (GJF) characterized with their
      alarming rapid growth and gross disfigurement is less frequently identified.
      MATERIALS AND METHODS: A 14-year review (1990-2004) of all fibroadenomas
      presented to the Outpatient Department was undertaken. Demographic data, duration
      of symptoms, size at presentation, the use of radiological, cytological and histo
      pathological modalities, surgical excision and follow up were all noted. Eight
      Hundred-Sixty-Four cases were diagnosed as fibroadenoma by both clinical and
      radiological examinations and confirmed by FNAC. Patients with fibroadenomas <2
      cm in size were followed up regularly in the out patients department, while those
      >2 cm underwent surgical excision. GJF were defined as those with >5 cm in
      diameter. RESULTS: The total number of excised fibroadenomas was 202 (23%), while
      the remaining662 (77%) fell into the follow up category. GJF were diagnosed in 9
      patients accounting for 4.5% of all excised fibroadenomas. Age ranged between 14
      23 years. CONCLUSION: However benign these lesions may appear, in view of the
      history of a sudden rapid breast enlargement as demonstrated in nearly all the
      clinical presentations, surgical excision remains the mainstay of treatment of
      such lesions in order to allow the previously compressed normal surrounding
      breast tissue to expand and retain its normal function and cosmetic appearance.
      The use of radiological modalities such as ultrasound and MRI may aid the
      diagnosis, limiting mammography to the older age group.

PMID- 23012083
TI  - Teaching tips: twelve tips for making case presentations more interesting.

PMID- 23012084
TI  - An audit of assessment tools in a medical school in eastern saudi arabia.
AB  - BACKGROUND: Assessment has a powerful influence on curriculum delivery. Medical
      instructors must use tools which conform to educational principles, and audit
      them as part of curriculum review. AIM: To generate information to support
      recommendations for improving curriculum delivery. SETTING: Pre-clinical and
      clinical departments in a College of Medicine, Saudi Arabia. METHOD: A self
      administered questionnaire was used in a cross-sectional survey to see if
      assessment tools being used met basic standards of validity, reliability and
      currency, and if feedback to students was adequate. Excluded were cost,
      feasibility and tool combinations. RESULTS: Thirty-one (out of 34) courses were
      evaluated. All 31 respondents used MCQs, especially one-best (28/31) and
      true/false (13/31). Groups of teachers selected test questions mostly. Pre
      clinical departments sourced equally from "new" (10/14) and "used" (10/14) MCQs;
      clinical departments relied on 'banked' MCQs (16/17). Departments decided pass
      marks (28/31) and chose the College-set 60%; the timing was pre-examination in
      13/17 clinical but post-examination in 5/14 pre-clinical departments. Of six
      essay users, five used model answers but only one did double marking. OSCE was
      used by 7/17 clinical departments; five provided checklist. Only 3/31 used
      optical reader. Post-marking review was done by 13/14 pre-clinical but 10/17
      clinical departments. Difficulty and discriminating indices were determined by
      only 4/31 departments. Feedback was provided by 12/14 pre-clinical and 7/17
      clinical departments. Only 10/31 course coordinators had copies of examination
      regulations. RECOMMENDATIONS: MCQ with single-best answer, if properly
      constructed and adequately critiqued, is the preferred tool for assessing theory
      domain. However, there should be fresh questions, item analyses, comparisons with
      pervious results, optical reader systems and double marking. Departments should
      use OSCE or OSPE more often. Long essays, true/false, fill-in-the-blank-spaces
      and more-than-one-correct-answer can be safely abolished. Departments or teams
      should set test papers and collectively take decisions. Feedback rates should be
      improved. A Center of Medical Education, including an Examination Center is
      required. Fruitful future studies can be repeat audit, use of "negative
      questions" and the number of MCQs per test paper. Comparative audit involving
      other regional medical schools may be of general interest.

PMID- 23012085
TI  - Selection of medical students and its implication for students at king faisal
      university.
AB  - The appropriate selection of medical students is a challenging task. It requires
      that important assessment criteria principally based upon cognitive skills that
      include the matriculation and admission test scores of the applicants be
      fulfilled. Non-cognitive skills are also important, but used to a lower degree
      include intellectual flexibility, inquisitiveness, critical reasoning, logical
      thinking, tolerance, ability to cope with uncertainty and problem solving. Other
      criteria that are also considered important for selection include personal
      qualities and attitudes of the applicants that reflect directly on doctor-patient
      relationship. In contrast, such demographic factors as age, gender, race,
      religion, socio-economic status and schooling should not influence the selection
      process. The admission criteria adopted at King Faisal University Medical College
      focus basically on cognitive criteria. Other criteria whether non-cognitive or
      personal quality assessment are also taken into account through interviews and
      completed questionaires.

PMID- 23012087
TI  - Avian influenza: reasons for concern and the challenges ahead.

PMID- 23012088
TI  - Health care professionals' knowledge on home health care in Al-khobar and Al
      dammam.
AB  - OBJECTIVE: To survey self-reported knowledge of home health care (HHC) services
      of health care professionals in Al-Khobar and Al-Dammam. METHODS: A specially
      developed questionnaire was used to conduct a cross-sectional study to find out
      how knowledgeable 11 hospital administrators, 16 PHHC medical directors, and 637
      health care team were of HHC services. RESULTS: When asked whether they knew of
      HHC services, 90.9% of medical directors, 62.5% of primary health care center
      directors, 83.1% of physicians, 92.9% of nurses, 98.6% of physiotherapists, 95.9%
      of social workers, and 57.6% of the health team members replied that they did,
      although this knowledge was very scanty. Health care workers' source of
      information on HHC services was hospital work (65.0%) while administrators'
      sources were journals (65.0%). Only 11.1% of the administrators and 30.3% of the
      health team members indicated having had HHC training from university, and 3.7%
      of administrators and 20.4% of health team members indicated having attended a
      HHC lecture or symposium. The only finding with significant difference of
      responses (p<0.001) was on the knowledge of HHC services among health care
      professionals. All other responses showed no significant differences between
      them. No significant differences in the responses were found between the two
      groups of administrators. CONCLUSIONS: Health professionals and administrators
      showed little knowledge of HHC services. The main source of HHC information for
      health professionals was from their hospital experience while administrators
      learned more about HHC services from medical journals. RECOMMENDATIONS: HHC
      training centers must be set up in Saudi Arabia. Home health care concepts and
      skills should be part of the regular health science undergraduate curriculum.

PMID- 23012086
TI  - Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS)
      in attention-deficit/hyperactivity disorder suggests a generalized differential
      ontogenic pattern from controls.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral
      disorder of childhood. Preliminary studies with proton magnetic resonance
      spectroscopy ((1)H-MRS) of the brain have reported differences in brain
      metabolite concentration-to-Cr ratios between individuals with ADHD and
      unaffected controls in several frontal brain regions including anterior cingulate
      cortex. Using multivoxel (1)H-MRS, we compared 14 individuals affected with ADHD
      to 20 individuals without ADHD from the same genetic isolate. After controlling
      by sex, age, and multiple testing, we found significant differences at the right
      posterior cingulate of the Glx/Cr ratio density distribution function between
      ADHD cases and controls (P < 0.05). Furthermore, we found several interactions of
      metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr
      ratios at the left posterior cingulate, and NAA/Cr at the splenius, right
      posterior cingulate, and at the left posterior cingulate. We also found a
      differential metabolite ratio interaction between ADHD cases and controls for
      Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr,
      Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant
      differences between ADHD cases and controls; (2) differences of these metabolite
      ratios between ADHD cases and controls evolve in specific and recognizable
      patterns throughout age, a finding that replicates previous results obtained by
      structural MRI, where is demonstrated that brain ontogeny follows a different
      program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right
      striatum, interact in a differential way between ADHD cases and controls. As a
      whole, these results replicate previous 1H-MRS findings and add new intriguing
      differential metabolic and ontogeny patterns between ADHD cases and controls that
      warrant further pursue.

PMID- 23012089
TI  - Prescribing patterns for acute respiratory infections in primary health care,
      aseer region, saudi arabia.
AB  - OBJECTIVE: The objective of this study was to identify the patterns of
      prescribing for Acute respiratory infections in patients attending primary health
      care centers in the Aseer region, southwestern Saudi Arabia.  MATERIALS
      #ENTITYSTARTX00026; METHODS: This study was conducted at primary health care
      centers in the Aseer region during November 2003. A master sheet designed by the
      investigator was distributed to all the working physicians in the primary health
      care center in the Aseer region. The master sheet included the age, sex,
      complaints, signs, clinical diagnosis and the type of medications prescribed.
      Physicians were asked to include all patients attending on 17(th) November 2003,
      and send the master sheet to the Technical Supervision Unit at Primary Care
      Department, General Directorate of Health Affairs. Data of the master sheet was
      entered and analyzed by using SPSS. RESULTS: The total number of patients
      attending with acute respiratory infections(ARIs) was 3000 which represented 25%
      of the patients attending primary health care centers that day. Children formed
      60% of the total number of cases. Regarding symptoms and signs, it was found that
      70% had a cough, 59% had a runny nose, and 43% had a sore throat . The common
      cold was the most common diagnosis (42%). Antipyretics, antihistamines,
      antibiotics and antitussives were prescribed for 78%, 48%, 45% and 25%
      respectively. Statistical analysis using logistic regression revealed that the
      higher the temperature, the more severe the throat congestion and the presence of
      exudates on pharynx, the higher the likelihood to prescribe antibiotics.
      CONCLUSION: In this study, it was found that the prescription of all drugs for
      ARIs was still high in spite of the fact that these conditions are self-limiting.
      To rationalize prescribing for ARI, implementation of the national protocol for
      diagnosis and treatment of ARIs is mandatory. Further studies to explore the
      physician's knowledge, attitudes and behavior concerning prescribing for ARI is
      strongly recommended.

PMID- 23012090
TI  - Severe malaria in sudanese children: clinical aspects and prognosis in
      hospitilized patients.
AB  - OBJECTIVE: To asssess the epidemiology, clinical presentations, disease
      mangement, outcome and risk factors associatted with severe malaria in children
      in four hospitals in Sudan. METHODS: Follow-up prospective design was used to
      fulfil the objectives of the study in four hospitals: Omdurman paediatrics
      hospital, located in the capital (Khartoum) compared to Madani, Gadarif and
      Sennar hospitals located in other states. THE RESULTS: Total admission of severe
      malaria was 543 children representing 21% of all paediatric admissions, and 12%
      of malaria outpatient cases. Median age of children with severe malaria was 48
      months. 93% of children with severe malaria died before the age of 9 years. Case
      fatlality rate was 2.6%. The risk of dying because of delay was four times more
      than when there was no delay , 95% CI (1.5 - 14.3). Other risks of death were
      severe malaria associated with coma, inability to sit or eat and hyperpyrexia.
      Omdurman hospital in Khartoum State in the capital, had the highest case
      management performance percentage compared to other regional hospitals.
      CONCLUSIONS: In view of this, it can be argued that deaths due to severe malaria
      could be reduced by improving health management and planning with the
      redistribution of resources (including consultants) at the central and regional
      levels and the conduct of proper training programs on the management of severe
      malaria at all levels. Raising the awareness of parents about seeking treatment
      for malaria early in order to avoid unnecessary deaths is vital.

PMID- 23012091
TI  - Breast infections in non-lactating women.
AB  - BACKGROUND: Breast infection in lactating mothers is a common entity which in the
      majority of cases can be explained by ascending infections. However, it has been
      noticed that the number of non lactating women presenting with breast abscesses
      is rising. This study attempts to explore the sensitivity pattern of organisms
      and underlying cause of breast infections in non-lactating women. MATERIALS AND
      METHODS: This review was undertaken at King Fahd of the University, Alkhobar,
      Saudi Arabia between 1991-2003. All patients presenting with breast infections
      were included. Medical records, operative notes, cultures, histopathology reports
      and outcome were reviewed. RESULTS: The number of patients presenting with breast
      infections accounted for 179(3.5%) out of the total number of patients 6314 with
      variable breast complaints. Infection occurred in 136(76%) lactating women (Group
      I) ,while Non lactating (Group II) breast infections accounted for 43(24%). Age
      ranged from 24 years to 52 years. Underlying clinical conditions were found in 26
      patients(60%) in Group II namely granulomatous mastitis13(50%), duct ectasia4
      (15.3%), pregnancy3(11.5%), fat necrosis1(3.8%), diabetes3 (11.5%) and breast
      cancer 2(7.6%). The pattern of culture results was different in the two groups,
      from differing causative organisms namely staphylococcus aureus as the commonest
      organism in both groups, in comparison to such uncommon organisms as Klebsiella
      pneumonae, Peptococcus magnus, Streptococcus group B, Entro-bacter cloacae,
      Methicillin resistant staphylococcus aureus (MRSA) and Mycobacterium tuberculosis
      occurring in group II only. Fortunately, all organisms were sensitive to
      antimicrobial therapy. CONCLUSION: Breast infection in non-lactating women is an
      infrequent but recognized clinical entity that deserves special attention. An
      underlying clinical condition should always be sought and treated. Indeed, in
      addition to cultures, radiological modalities such as ultrasonographic imaging
      may provide specific diagnosis and aid the management.

PMID- 23012092
TI  - Antibiotic susceptibility patterns of different bacteria isolated from patients
      with ventilator associated pneumonia (vap).
AB  - OBJECTIVE: Ventilator associated pneumonia (VAP) is a frequent complication of
      mechanical ventilation (MV) and it is a leading cause of death in MV patients.
      The development of VAP has been demonstrated as being due to aspiration of
      oropharyngeal secretion, ventilator tubing condensate, or gastric contents that
      are colonized with pathogenic microorganisms. The aim of the present study is to
      isolate and identify bacteria that cause VAP and to study antibiotic
      susceptibility. MATERIAL AND METHODS: This study was carried out on 95 patients
      who fulfilled the diagnostic criteria for VAP. Quantitative cultures of
      endotracheal aspirates (EA) using a cut-off point of 10(6) cfu/ml was done.
      RESULTS: The microbiological results revealed that gram negative bacilli were the
      most common bacterial agents responsible for VAP and accounted for 78.8% of all
      the causative agents. The most common isolated organisms were Klebsiella
      pnemouniae (30.9 %) followed by Pseudomonas aeruginosa (22.5%), Staphylococcus
      aureus (21.2%), Eschericia coli (12.8 %), Proteus spp. (9.8%), and Citrobacter
      spp. (2.8%). Blood cultures were positive in 25.9% of patients with Klebsiella
      pnemouniae in about 33.3%. CONCLUSION: From this study, it can be concluded that
      VAP is an important nosocomial infection. EA is a simple procedure to obtain
      respiratory samples and perform sensitivity testing in patients with VAP. Also,
      the commonest cause of VAP is gram negative bacilli.

PMID- 23012093
TI  - Prevalence and risk factors of asthma among wad medani basic school children,
      gezira state, Sudan.
AB  - OBJECTIVES: Childhood asthma is said to be under-estimated and under-diagnosed in
      tropical countries including Sudan. The prevalence of asthma worldwide is
      increasing. The objective of this study was to determine the prevalence and the
      trigger factors of asthma among Wad Medani basic school children. METHODS: A
      cross-sectional study was conducted during school year 2000-2001. The study group
      was selected by stratified proportional random sampling according to their age,
      sex and localities.Data was collected utilizing a pre-tested questionnaire
      addressing the history of asthma and its trigger factors (sample-2, 2002).
      RESULTS: The results revealed that asthma is the ninth of the most common
      diseases among the school children, having a prevalence of 9.2% (sample 1) and
      17.9% (sample 2), the main trigger factors of which are dust, cold bats, exercise
      and smoke respectively. CONCLUSION: Asthma among school children is a common
      problem that should be considered when planning preventive school health
      programmes.

PMID- 23012094
TI  - Professional attitudes and career choices of female medical laboratory technology
      students and graduates: experience from eastern saudi arabia.
AB  - OBJECTIVES: To conduct a survey of the medical laboratory technology senior
      students, interns and graduates in King Faisal University to gather descriptive
      data on what students and graduates felt about their chosen profession and their
      career goals for the next five years. MATERIAL AND METHODS: The study design was
      a survey. A questionnaire was specially designed for this purpose in order to
      gather information on the professional attitudes and career choices of the
      participants. The study period was one year, from January I, 2004 to December 31,
      2004. A stratified random sample with proportional allocation was selected and a
      self-administered 17-item questionnaire was distributed. A 5-point Likert scale
      ranging from 1, strongly agree to 5 strongly disagree was created for the
      questions as well as two multiple-choice questions. 115 questionnaires were
      distributed to the available senior students, interns and graduates, 111 were
      returned completed. Statistical analysis was performed using the statistical
      package for the social sciences (SPSS) PC + Software program. RESULTS:
      Respondents indicated a high level of satisfaction with their chosen profession
      as indicated by the ratings on the different questions relating to the profession
      of MLT. Their career goals were mainly working in a hospital laboratory as
      medical technologists (57.7%), and continuing their postgraduate education
      (38.7%). CONCLUSION AND RECOMMENDATIONS: MLT students and graduates expressed
      satisfaction with their chosen profession as evidenced by their responses
      assessing professional attitudes. Their career goals were mainly working at the
      bench level as Medical Laboratory Technologists in a hospital laboratory and
      postgraduate education.

PMID- 23012095
TI  - Family medicine is alive and well in the gulf.

PMID- 23012097
TI  - Assessment of care for type 2 diabetic patients at the primary care clinics of a
      referral hospital.
AB  - BACKGROUND: There is rapid increase in the incidence of Diabetes Mellitus (DM) in
      the Kingdom of Saudi Arabia (KSA), as in other countries. An optimal care of
      diabetic patients depends on the health care providers as well as the type of
      health care setting. Due to the severity of chronic complications in Type 2
      diabetic patients, it is essential to assess both the practices of the providers
      and the patient outcomes at any clinical setting. OBJECTIVES: To assess the
      screening patterns of diabetes associated health care problems in primary care
      clinics of King Khalid University Hospital (KKUH) and while compare them to the
      current diabetes clinical practice recommendations of American Diabetes
      Association (ADA). METHODS: The retrospective review of charts of 103 eligible
      patients who attended the primary care clinics of KKUH over a 3 year-period
      (1/12001-31/12/2003) had provided 99 type 2 diabetic patients. The study
      variables included demographic data, complications, treatment, the provider
      screening practices (measurements of HbA1c, BP, Lipid profile, number of eye and
      foot examination). From these data, the frequency of provider screening tests,
      normalized by patient-year could be compared with the ADA guidelines. RESULTS:
      The mean age of 99 type 2 diabetic patients was 57 years, with a mean BMI of 30.8
      kg/m2 and with a mean duration of diabetes of 11.8 years. Many had comorbidites
      or complications: 25% had retinopathy, 17.2% had nephropathy, and 12.1% had
      neuropathy. The HbA1c level of <= 7.0 was maintained by only 24.7% of patients.
      About 85% of patients had >= 1 lipid profile, during their follow-up period.
      During 2(nd) and 3(rd) year follow up only 30% had >= 1 HbA1c measurement and
      26.5% (at 2(nd) year), 22%(at 3(rd) year) had >= 1 foot examination. The
      proportion of patients, who had >= 1 eye examination was also reduced during
      their follow up. The provider practice screening results per patient-year was
      well below the specified guidelines of ADA. CONCLUSION: Type 2 diabetic patients
      care at our primary care clinics did not adhere to the guidelines of ADA. The
      reasons for the deficiencies were not evident from this study. More detailed
      studies are needed to find out the relevant causes for the lack of adequate
      diabetic care at primary care clinics.

PMID- 23012096
TI  - Outpatient management of type 2 diabetic patients: a review of evidence-based
      literature.
AB  - Diabetes mellitus is a common, serious, and treatable disease. Good control is
      associated with fewer complications. The impact of the disease on the patient,
      family and the community psychologically and physically is staggering. This paper
      aims to update the reader on certain issues related to the management of
      diabetes. Recent criteria for the diagnosis are presented followed by non
      pharmacological and pharmacological management, glycemic monitoring, prevention,
      continuity of diabetes care and the control of co-morbidities. Throughout, as far
      as possible, the best available evidence was used.

PMID- 23012098
TI  - Knowledge & practices of childhood immunization among primary health care
      providers in riyadh city: part ii - precautions and contraindications to
      vaccination.
AB  - OBJECTIVES: To assess 1) how aware those who administer vaccines in the primary
      health care centres (PHCs) are of the appropriate precautions and
      contraindicaitons of vaccines and 2) the extent to which their practice complies
      with standards, and 3) the correlation between the levels of knowledge and
      practice on one hand with the duration of practice and attendance at a training
      course on vaccination on the other hand, for physicians and nurses separately.
      METHODS: A self-adminstered questionnaire including 16 statements related to
      knowledge and practice of precautions and contraindications of vaccines was
      distributed among workers in 50 MOH PHCs in Riyadh. RESULTS: 506 questionnaires
      were returned, only 331 were completed for this part of the study giving a
      response rate of almost 65%. However, the statement-specific response rate
      varied. Except for a few, most statements were correctly responded to by a
      majority of the respondents reflecting adequate knowlegde and appropriate
      practice. Experience in dealing with vaccination, and formal training in
      vaccination were not statistically significantly associated with the responses of
      both physicians and nurses. CONCLUSION: Inspite of the limitations of this study
      it could be fairly concluded that the overall knowledge and practices regarding
      precautions and contraindications of childhood immunizations among the primary
      care providers surveyed was good. Significant gaps still exist. This underlines
      the need for continuous training and supervision of health care providers who
      deal with the immunization of children.

PMID- 23012099
TI  - The profile of long-term care patients in Al-khobar and dammam, saudi arabia.
AB  - OBJECTIVES.: To find out the profile of patients who stay more than 20 days in
      hospital in Al-Khobar and Al-Dammam.  METHODS.: A cross sectional descriptive
      study was designed using a questionnaire completed by health care providers
      (physicians, nurses, physiotherapists, and social workers) of a random sample of
      159 patients out of 318 patients identified as having stayed in the hospital for
      more than 20 days.  RESULTS.: The mean length of stay of the patients were 358.6
      +/-776 days in government hospitals, and 1014.4 +/-1018.3 days in private
      hospitals. Patients were seen as stable by their doctors, 66.7% in government
      hospitals and 93.9% in private hospitals (statistically significant different at
      p<0.001. Physicians agreed that about two thirds of the patients could have been
      managed at home. 57.2% of the patients had no active problems. Diseases of the
      nervous system and sense organs accounted for 67.9% of the diagnoses, followed by
      endocrine, nutritional, and metabolic diseases (37.1%), diseases of the
      circulatory system (32.7%), and neoplasms (1.9%). Diabetes mellitus was the
      commonest illness making up 53.2% and 57.1% of the long-term patients in private
      and government hospitals respectively. The active problems of 25% and 23.5% of
      the patients was tracheostomy care and ventilation respectively.  CONCLUSIONS.:
      Long-term patients tended to stay longer in private hospitals than in government
      hospitals, had diseases related to the nervous and endocrine systems and
      nutritional metabolism, were in stable condition with no active problems, and
      could thus, be managed at home.

PMID- 23012101
TI  - Pattern of haemoglobin among high and low altitude children of southwestern saudi
      arabia.
AB  - OBJECTIVE: To determine the levels of haemoglobin and to study some of its
      correlates in high and low altitude children of the Southwestern region of the
      kingdom of Saudi Arabia. METHODS: A cross-sectional study of 1331 Saudi children
      aged 1-15 years born and living permanently at high altitude (2800-3150 m above
      sea level) and 1185 Saudi children of comparable age born and living permanently
      at low altitude (500 m above sea level) was conducted. Their haemoglobin levels
      were estimated by using cyanmethaemoglobin method and correlated with age, weight
      and height. RESULTS: The mean haemoglobin levels were significantly greater in
      highland children compared with lowland children (p<0.0001 for both boys and
      girls). There were no significant differences in the mean haemoglobin levels
      between boys and girls at each study site. In both high and lowland children
      haemoglobin levels rose with age although lowland girls showed a drop beyond the
      age of 11-13 years and highland girls did not show any increase beyond the age of
      9-11 years. In both boys and girls haemoglobin was found to be positively and
      significantly correlated with weight and height. CONCLUSIONS: The difference in
      haemoglobin levels between high and lowland children was attributed to the
      combined effect of high altitude hypoxia and the higher incidence of tropical
      infections among lowland children.

PMID- 23012100
TI  - A retrospective study of some clinical and epidemiological features of impetigo
      patients seen in dermatology clinic in the eastern province of saudi arabia.
AB  - BACKGROUND: Impetigo is a common contagious superficial skin infection, most
      frequently seen in children. OBJECTIVES: To determine the clinical and
      epidemiological features of impetigo patients seen in the dermatology clinic of
      King Fahd Hospital of the University (KFHU). METHODS: This is a retrospective
      study of impetigo patients seen in the dermatology clinic at KFHU, Al-Khobar,
      Saudi Arabia, during the period January 1990 to December 2001. Data collected
      from patients' records included demographic features, clinical features,
      investigations and treatment. Only patients with positive skin culture were
      included in the study. RESULTS: The total number of patients included in this
      study was 65 and constituted 0.08% of all the cases presenting with dermatology
      problems in that period. Males were affected by impetigo more than the females,
      giving a ratio of 1.7:1. The majority of the cases occurred in children less than
      10 years of age, and the bullous form of impetigo was the predominant type. The
      sites affected by impetigo were mainly the extremities and the face. The highest
      number of patients was seen during summer and Staphylococcus was the most common
      causative agent. CONCLUSION: The incidence and prevalence of impetigo in Saudi
      Arabia is unknown and can be best defined by prospective community-based study.
      The diagnosis and management of impetigo is best achieved by microbiological
      cultures and sensitivities laboratory investigations.

PMID- 23012102
TI  - The role of medical students in patient education to promote home management of
      diabetes mellitus in wad medani town, Sudan 2003.
AB  - INTRODUCTION: Faculty of Medicine University of Gezira, utilized a community
      based educational strategy. In the module primary health care centre practice and
      family medicine (PHCCP & FM), each student is assigned a family for whom priority
      health problems are identified and education given accordingly. OBJECTIVES: To
      provide, through medical students, health education to diabetics in the assigned
      families and to assess the impact of the students' intervention. METHODS: THIS IS
      LONGITUDINAL INTERVENTIONAL STUDY WHICH WAS CONDUCTED IN THREE STAGES: training
      of medical students, education to diabetic patients and evaluation of the
      intervention. RESULTS: There was a highly significant difference in the students'
      knowledge and skills including communication skills on the home management of
      diabetes mellitus. Diabetics in the families were 80(3.3%), 42 (52.5%) females,
      38 (47.5%) males. Their ages ranged between 22-78 years. Illiteracy rate was 9
      (11.2%), most of the families' incomes ranged from low to middle, only 25% were
      of the high income bracket. More than half 47(58.7%) of the diabetics reported
      complications of diabetes. Eye complications 6 (7.5%), peripheral neuropathy 15
      (18.7%), foot sepsis 4 (4.5%), urinary tract infection 11 (13.7%), renal failure
      2 (2.5%), others 9 (11.2%). There was a highly significant improvement in the
      knowledge, attitudes and practices of the diabetics, as a result of the student
      intervention. These included compliance to treatment, adherence to diabetic diet,
      regular care of the feet, knowledge of major diabetic complications, knowledge of
      signs of hypoglycaemia, and home management of hypoglycemia. Ten cases with
      serious complications were referred to Wad Medani teaching hospital.

PMID- 23012104
TI  - Obesity and physical inactivity among saudi children and youth: challenges to
      future public health.

PMID- 23012103
TI  - GILT expression in B cells diminishes cathepsin S steady-state protein expression
      and activity.
AB  - MHC class II-restricted Ag processing requires protein degradation in the
      endocytic pathway for the activation of CD4(+)  T cells. Gamma-interferon
      inducible lysosomal thiol reductase (GILT) facilitates Ag processing by reducing
      protein disulfide bonds in this compartment. Lysosomal cysteine protease
      cathepsin S (CatS) contains disulfide bonds and mediates essential steps in MHC
      class II-restricted processing, including proteolysis of large polypeptides and
      cleavage of the invariant chain. We sought to determine whether GILT's reductase
      activity regulates CatS expression and function. Confocal microscopy confirmed
      that GILT and CatS colocalized within lysosomes of B cells. GILT expression
      posttranscriptionally decreased the steady-state protein expression of CatS in
      primary B cells and B-cell lines. GILT did not substantially alter the expression
      of other lysosomal proteins, including H2-M, H2-O, or CatL. GILT's reductase
      active site was necessary for diminished CatS protein levels, and GILT expression
      decreased the half-life of CatS, suggesting that GILT-mediated reduction of
      protein disulfide bonds enhances CatS degradation. GILT expression decreased the
      proteolysis of a CatS selective substrate. This study illustrates a physiologic
      mechanism that regulates CatS and has implications for fine tuning MHC class II
      restricted Ag processing and for the development of CatS inhibitors, which are
      under investigation for the treatment of autoimmune disease.

PMID- 23012105
TI  - Pregnancy outcome of gestational diabetic mothers: experience in a tertiary
      center.
AB  - BACKGROUND: Carbohydrate intolerance is the most common metabolic complication of
      pregnancy. Gestational Diabetes Mellitus (GDM) poses numerous problems for both
      mother and fetus. The objectives of this study are to find out the incidence of
      gestational diabetes mellitus in pregnant women and their pregnancy outcomes. It
      was also to discover the risk factors for the admission of neonates to the
      Neonatal Intensive Care Unit (NICU). DESIGN AND PATIENTS: A hospital-based
      prospective study performed at King Khalid University hospital (KKUH), where 685
      pregnant women who were diagnosed with gestational diabetes mellitus, out of 8000
      pregnant women registered between January 2000 - December 2001, were followed and
      their outcomes studied. RESULTS: The incidence of gestational diabetes mellitus
      was found to be 8.6% (95% C.I: 8.1, 9.3). There were 511 (74.6%) spontaneous
      vertex deliveries, and 148 (21.6%) were delivered by lower segment cesarean
      section. Maternal morbidity in these women was 1.2%. A total of 697 babies were
      delivered by these 685 women, out of whom 675 were singleton pregnancies, 9 sets
      of twins and one set of quadruplets. Six-hundred-eighty-seven babies were born
      alive, 7 babies died in utero and 3 died in the neonatal period. The incidence of
      neonatal intensive care admission was 4.9%. The mean length of stay in the NICU
      was 16 days. The commonest cause of neonatal NICU admission was
      hyperbilirubinemia (41.2%). The risk factors for NICU admission were delivery by
      non SVD procedure (RR: 4.6, 95% C.I:2.8, 7.7), preterm deliveries, (RR: 4.6, 95%
      C.I.:2.7, 7.7), and induction of labor (RR: 2.5, 95% C.I: 1.4, 4.5). CONCLUSION:
      The observation and quantification of maternal outcomes with gestational diabetes
      mellitus are necessary, so that proper measures could be taken to reduce
      complications during delivery and the neonatal period and thereby, minimize
      particularly NICU admission rate.

PMID- 23012106
TI  - Seropositivity of Chlamydia trachomatis among saudi pregnant women in makkah.
AB  - OBJECTIVE: To determine the seroprevalence rates of immunoglobulin G (IgG) and
      immunoglobulin M (IgM) to Chlamydia trachomatis in Saudi pregnant women. SUBJECTS
      AND METHODS: Using enzyme-linked immunosorbent assay (ELISA), a total of 1600
      serum samples were tested for antibodies to Chlamydia trachomatis known to cause
      a variety of clinical syndromes in women and newborn infants. RESULTS: Chlamydia
      trachomatis IgG antibodies were detected in 8.7% and IgM antibodies were found in
      1.5% of different age groups. CONCLUSION: Pregnant Saudi women have low
      prevalence rate of Chlamydia trachomatis IgG antibodies and lower prevalence for
      Chlamydia trachomatis IgM.

PMID- 23012107
TI  - Dermatoses in obese female schoolchildren in the Al-khobar area, eastern saudi
      arabia.
AB  - OBJECTIVES: The aim of this study was to determine the most frequent skin
      disorders in obese female schoolchildren in primary and intermediate schools in
      the Al-Khobar area, Eastern Saudi Arabia. METHODOLOGY: This was a cross-sectional
      study conducted in the Al-Khobar area. It involved 2239 female schoolchildren
      randomly selected from 30 regular public and private primary and preparatory
      schools. A multi-stage stratified random sampling technique with proportional
      allocation was used. Data was collected using clinical examination and
      anthropometric measurements. RESULT: THE SKIN DISEASES THAT WERE MOST COMMON IN
      OBESE SCHOOLCHILDREN WERE: dandruff, acne, xerosis, acanthosis nigricans,
      folliculitis, alopecia, stria distensae (stretch marks) and callosity.
      CONCLUSIONS AND RECOMMENDATIONS: obesity is associated with specific skin
      disorders. Health education programs on skin diseases and obesity should be
      provided to all schoolchildren, their families and teachers.

PMID- 23012108
TI  - Patterns of childhood cancer in children admitted to the institute of nuclear
      medicine, molecular biology and oncology (inmo), wad medani, gezira state.
AB  - INTRODUCTION: Cancers form one of the major causes of death in children between
      the ages of one and 15 years. They differ markedly from adult cancers in their
      nature, distribution and prognosis. The patterns of childhood cancers in America
      and Europe are almost the same, with leukemia and central nervous system tumors
      accounting for over one-half of the new cases. In contrast, lymphoma is the most
      common prevailing cancer of this age group in Africa. OBJECTIVE: The objective of
      this study is to determine the patterns of childhood cancers in Gezira State,
      Central Sudan. It is a retrospective study using hospital records. All children
      with cancer, aged 1 - 15 years diagnosed by means of histological or cytological
      examination admitted to the Institute of Nuclear Medicine, Molecular Biology and
      Oncology from May 1999 - December 2004 were included in the study. RESULTS: The
      results showed a pattern of childhood lymphoma as the most common cancer (42.8%)
      followed by acute lymphoblastic leukemia (19.8%) and kidney tumor (12.8%). The
      prevalence of cancer was found to be higher among boys (64.7%) than girls (35.3%)
      with a rate of 1.8:1. Most of the children admitted with cancer were from rural
      areas (66.1%) compared to (33.9%) from urban areas. CONCLUSION: Lymphoma, acute
      lymphoblastic leukemia and bone tumor commonly occurred in children above 5 years
      in contradistinction to kidney tumor and retinoblastoma which was prevalent in
      children less than 5 years of age.

PMID- 23012109
TI  - Current situation of continuing medical education for primary health care
      physicians in Al-madinah Al-munawarah province, saudi arabia.
AB  - OBJECTIVE: In the health care system, continuing medical education (CME) is
      concerned with the maintenance, improvement, and promotion of health care
      provided by physicians. The objectives of this study are: to assess the
      knowledge, attitude and practice of Primary Health Care (PHC) physicians of CME,
      and to analyze the utilization of Continuing Medical Education (CME) program.
      MATERIAL AND METHODS: This is a cross-sectional descriptive study with an
      analytic component. A two-stage stratified random sampling was done on 189 PHC
      physicians from 76 PHC centers in the Al Madina, Al Munawarah City. One Hundred
      Fifteen physicians actually took part in the study. RESULTS: Only 3.5% of the
      physicians were Saudi, 2% had PHC postgraduate qualification in Primary Health
      Care and 75% had had basic training during their practice. The study showed that:
      (1) PHC physicians who worked in a group evaluated Medical Education Center (MEC)
      better than those who worked alone (p =0.0052). (2)Those who were aware of the
      presence of the MEC gave MEC contribution a better grade in evaluation than those
      who were not (p=0.0001). (3) PHC physicians who had more experience in medical
      practice evaluated CME achievement with a better grade than those who had less
      experience (p = 0.0173). (4) PHC physicians working in groups evaluated CME
      achievement with a better grade (p = 0.0330). (5) Those who were attached to the
      hospitals evaluated CME achievement with a better grade (p = 0.0392). (6) Those
      who attended activities outside PHC centers evaluated CME achievements better
      than those who did not (p = 0.0202). CONCLUSION: FROM THE RESULTS IT WAS
      CONCLUDED THAT: (1) There are many PHC physicians who were unaware of CME
      activities in their area of work and therefore tend to be unhappy with MEC
      contribution. (2) PHC physicians were not satisfied with MEC's contribution and
      with their CME's achievements. (3) PHC physicians felt the need for utilizable
      CME. (4) PHC physicians were not fully aware of the use of the internet, distance
      learning, and emails in CME.

PMID- 23012110
TI  - Perception of female students of king saud university towards premarital
      screening.
AB  - OBJECTIVES: The aim of this study was to investigate the perception of King Saud
      University female students towards the implementation of premarital screening
      (PMS) in the Kingdom of Saudi Arabia (KSA). METHODS: Two consecutive surveys on
      knowledge, attitudes and practice (KAP) were conducted two and nine months after
      the compulsory implementation of PMS in KSA in 1/1/1425H. The female students of
      King Saud University were given health education lectures before the survey. The
      first survey was done with a designed close-ended questionnaire distributed at
      pre and post stages of the health education lecture. However, the second one
      explored the participants' perception of the same items in open-ended questions
      summarized as a "consensus statement". In fulfillment of their demands, the
      signed statement was mailed to the legislative authorities. RESULTS AND
      DISCUSSION: A total of 140 university female students attended the first lecture.
      The response rate for both pre and post lecture surveys were 132 (94.3%) and 128
      (91.4%) respectively. A total of 112 out of 132 (84.8%) students in the pre test
      and 111 out of 128 (86.7%) in the post-test were single. Of the married students
      7/20 (35.0%) and 7/17 (41.2%) in pre and post tests had previously had PMS
      screening. The attitude of the students towards PMS was generally positive. One
      hundred and eight (81.8%) in the pre test and 110 (85.9%) in the post test saw
      the importance of PMS in controlling the commonest hereditary diseases. However,
      a smaller percentage of students (69.7% and 75.0%) in pre and post lecture
      respectively were in favor of the compulsory application of PMS in KSA. In spite
      of the positive attitude of all the students in the pre and post tests, fears
      were expressed towards the confidentiality of PMS test results and it was felt
      that social and psychological problems would ensue from abnormal results. This,
      however, does not represent the feeling of the entire population in KSA since the
      participants of the study formed a select group. The second awareness lecture was
      attended by 319 students from the College of Education. They were subsequently
      requested to state their perceptions of PMS application with regard to its
      content, nature and method of application in KSA in their own words. The
      collected forms were summarized into a "consensus statement" and signed by all
      319 students. They felt that the scope of PMS should be extended to investigate
      and screen for other diseases especially sexually transmitted diseases that would
      adversely affect the health of members of the family and the community as a
      whole. Their worry about the lack of screening for other diseases may be because
      a majority of the study group were single and would, therefore, refuse to get
      married on account of the risks to their future offspring. In addition, it may
      reflect their knowledge of the effects of globalization on the transmission of
      diseases. CONCLUSIONS: Health education is an important means of improving the
      public's perception of newly-introduced health interventions. University students
      have a good perception of the compulsory implementation of PMS in KSA. Pre
      marital screening could be extended to include a broader spectrum of
      health/genetic disorders and will be useful for early identification and possible
      intervention as well as the prevention of complications.

PMID- 23012111
TI  - Attitudes of medical laboratory technology graduates towards the internship
      training period at king faisal university.
AB  - OBJECTIVES: The objective of this present survey was to look into the attitudes
      of medical laboratory technology (MLT) graduates towards the internship training
      period of the MLT Department, College of Applied Medical Sciences, King Faisal
      University. MATERIAL AND METHODS: A self-administered questionnaire was designed
      and distributed for this purpose. The study period was from December 1(st) 2002 -
      31(st) December 2004. Two-hundred questionnaires were distributed to recent
      graduates, and 115 were returned completed. RESULTS: All respondents agreed with
      the importance and necessity of the internship period, and felt it should not be
      reduced or eliminated. The most favorite laboratory where they liked to work was
      microbiology (70%). They all agreed that evaluation report with hospital staff
      and laboratory set up were vital in achieving the goals of the internship period.
      The majority stressed the significance of safety precautions and the application
      of theoretical knowledge before performing technical assignments. CONCLUSION: The
      respondents had very positive attitudes towards the internship-training period
      stressing its importance. The most favorite laboratory rotations were in rank
      order: Microbiology, Serology followed by Histotechnology, Hematology, Blood
      Banking and finally Clinical Chemistry. The majority of graduates had a very
      positive attitude also towards medical laboratory technology as a profession.

PMID- 23012112
TI  - Ruthenium(II/III)-based compounds with encouraging antiproliferative activity
      against non-small-cell lung cancer.
AB  - Hereby we present the synthesis of several ruthenium(II) and ruthenium(III)
      dithiocarbamato complexes. Proceeding from the Na[trans-Ru(III)(dmso)(2)Cl(4)]
      (2) and cis-[Ru(II)(dmso)(4)Cl(2)] (3) precursors, the diamagnetic, mixed-ligand
      [Ru(II)L(2)(dmso)(2)] complexes 4 and 5, the paramagnetic, neutral [Ru(III)L(3)]
      monomers 6 and 7, the antiferromagnetically coupled ionic alpha
      [Ru(III)(2)L(5)]Cl complexes 8 and 9 as well as the beta-[Ru(III)(2)L(5)]Cl
      dinuclear species 10 and 11 (L = dimethyl- (DMDT) and pyrrolidinedithiocarbamate
      (PDT)) were obtained. All the compounds were fully characterised by elemental
      analysis as well as (1)H NMR and FTIR spectroscopy. Moreover, for the first time
      the crystal structures of the dinuclear beta
      [Ru(III)(2)(dmdt)(5)]BF(4)?CHCl(3)?CH(3)CN and of the novel [Ru(II)L(2)(dmso)(2)]
      complexes were also determined and discussed. For both the mono- and dinuclear
      Ru(II) and Ru(III) complexes the central metal atoms assume a distorted
      octahedral geometry. Furthermore, in vitro cytotoxicity of the complexes has been
      evaluated on non-small-cell lung cancer (NSCLC) NCI-H1975 cells. All the mono-
      and dinuclear Ru(III) dithiocarbamato compounds (i.e., complexes 6-10) show
      interesting cytotoxic activity, up to one order of magnitude higher with respect
      to cisplatin. Otherwise, no significant antiproliferative effect for either the
      precursors 2 and 3 or the Ru(II) complexes 4 and 5 has been observed.

PMID- 23012113
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Executive summary.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The content of the executive summary is presented here to promote
      international discussion and collaboration by making the principles and standards
      recommended in the new EU Guidelines known to a wider professional and scientific
      community. Following these recommendations has the potential to enhance the
      control of colorectal cancer through improvement in the quality and effectiveness
      of screening programmes and services.

PMID- 23012114
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Professional requirements and training.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on professional requirements and training includes 23
      graded recommendations. The content of the chapter is presented here to promote
      international discussion and collaboration by making the principles and standards
      recommended in the new EU Guidelines known to a wider professional and scientific
      community. Following these recommendations has the potential to enhance the
      control of colorectal cancer through improvement in the quality and effectiveness
      of surveillance and other elements in the screening process, including multi
      disciplinary diagnosis and management of the disease.

PMID- 23012115
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Quality assurance in pathology in colorectal cancer
      screening and diagnosis.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on quality assurance in pathology in colorectal cancer
      screening and diagnosis includes 23 graded recommendations. The content of the
      chapter is presented here to promote international discussion and collaboration
      by making the principles and standards recommended in the new EU Guidelines known
      to a wider professional and scientific community. Following these recommendations
      has the potential to enhance the control of colorectal cancer through improvement
      in the quality and effectiveness of the screening process, including multi
      disciplinary diagnosis and management of the disease.

PMID- 23012116
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Annotations of colorectal lesions.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on quality assurance in pathology was supplemented by an
      annex describing in greater detail some issues raised in the chapter,
      particularly details of special interest to pathologists. The content of the
      annex is presented here to promote international discussion and collaboration by
      making the issues discussed in the guidelines known to a wider professional and
      scientific community.

PMID- 23012117
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Management of lesions detected in colorectal cancer
      screening.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on management of lesions detected in colorectal cancer
      screening includes 32 graded recommendations. The content of the chapter is
      presented here to promote international discussion and collaboration by making
      the principles and standards recommended in the new EU Guidelines known to a
      wider professional and scientific community. Following these recommendations has
      the potential to enhance the control of colorectal cancer through improvement in
      the quality and effectiveness of the screening process, including multi
      disciplinary diagnosis and management of the disease.

PMID- 23012118
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Introduction.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The first chapter deals with the evidence for the effectiveness of
      CRC screening; key operational parameters such as age-range, interval between two
      negative screening examinations, and some combinations of tests; and cost
      effectiveness. The content of the chapter is presented here to promote
      international discussion and collaboration by making the principles and standards
      recommended in the new EU Guidelines known to a wider professional and scientific
      community. Following these recommendations has the potential to enhance the
      control of colorectal cancer through improvement in the quality and effectiveness
      of the screening process, including multi-disciplinary diagnosis and management
      of the disease.

PMID- 23012119
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Colonoscopic surveillance following adenoma removal.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on colonoscopic surveillance following adenoma removal
      includes 24 graded recommendations. The content of the chapter is presented here
      to promote international discussion and collaboration by making the principles
      and standards recommended in the new EU Guidelines known to a wider professional
      and scientific community. Following these recommendations has the potential to
      enhance the control of colorectal cancer through improvement in the quality and
      effectiveness of surveillance and other elements in the screening process,
      including multi-disciplinary diagnosis and management of the disease.

PMID- 23012120
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Communication.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on communication includes 35 graded recommendations. The
      content of the chapter is presented here to promote international discussion and
      collaboration by making the principles and standards recommended in the new EU
      Guidelines known to a wider professional and scientific community. Following
      these recommendations has the potential to enhance the control of colorectal
      cancer through improvement in the quality and effectiveness of screening
      programmes and services.

PMID- 23012121
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Organisation.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on organisation includes 29 graded recommendations. The
      content of the chapter is presented here to promote international discussion and
      collaboration by making the principles and standards recommended in the new EU
      Guidelines known to a wider professional and scientific community. Following
      these recommendations has the potential to enhance the control of colorectal
      cancer through improvement in the quality and effectiveness of the screening
      process, including multi-disciplinary diagnosis and management of the disease.

PMID- 23012122
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Evaluation and interpretation of screening outcomes.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on evaluation and interpretation of screening outcomes
      includes 20 graded recommendations. The content of the chapter is presented here
      to promote international discussion and collaboration by making the principles
      and standards recommended in the new EU Guidelines known to a wider professional
      and scientific community. Following these recommendations has the potential to
      enhance the control of colorectal cancer through improvement in the quality and
      effectiveness of the screening process, including multi-disciplinary diagnosis
      and management of the disease.

PMID- 23012123
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Faecal occult blood testing.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on faecal occult blood testing includes 21 graded
      recommendations. The content of the chapter is presented here to promote
      international discussion and collaboration by making the principles and standards
      recommended in the new EU Guidelines known to a wider professional and scientific
      community. Following these recommendations has the potential to enhance the
      control of colorectal cancer through improvement in the quality and effectiveness
      of screening programmes and services.

PMID- 23012124
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Quality assurance in endoscopy in colorectal cancer
      screening and diagnosis.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The chapter on quality assurance in endoscopy includes 50 graded
      recommendations. The content of the chapter is presented here to promote
      international discussion and collaboration by making the principles and standards
      recommended in the new EU Guidelines known to a wider professional and scientific
      community. Following these recommendations has the potential to enhance the
      control of colorectal cancer through improvement in the quality and effectiveness
      of endoscopy and other elements in the screening process, including
      multidisciplinary diagnosis and management of the disease.

PMID- 23012125
TI  - European guidelines for quality assurance in colorectal cancer screening and
      diagnosis. First Edition--Principles of evidence assessment and methods for
      reaching recommendations.
AB  - Multidisciplinary, evidence-based guidelines for quality assurance in colorectal
      cancer screening and diagnosis have been developed by experts in a project
      coordinated by the International Agency for Research on Cancer. The full
      guideline document covers the entire process of population-based screening. It
      consists of 10 chapters and over 250 recommendations, graded according to the
      strength of the recommendation and the supporting evidence. The 450-page
      guidelines and the extensive evidence base have been published by the European
      Commission. The principles of evidence assessment and methods for reaching
      recommendations are presented here to promote international discussion and
      collaboration by making the principles and methods used in developing the
      guidelines known to a wider professional and scientific community. Following this
      methodology in the future updating of the guidelines has the potential to enhance
      the control of colorectal cancer through improvement in the quality and
      effectiveness of the screening process, including multidisciplinary diagnosis and
      management of the disease.

PMID- 23012126
TI  - New players for the new era: working together for the promotion of health.

PMID- 23012127
TI  - Leptin levels in normal weight and obese saudi adults.
AB  - OBJECTIVE: The purpose of the study was to measure serum leptin in normal weight
      and obese individuals, and assess its relation to anthropometric measures and
      metabolic indices. METHODS: The study was conducted at King Fahd Hospital of the
      University, Saudi Arabia, from January 2003 to June 2004. Subjects included in
      the study were all non-diabetic normotensive adults. Variables measured were body
      mass index (BMI), waist to hip ratio (WHR), blood pressure, serum leptin,
      insulin, glucose, and lipids. RESULTS: Included were 43 non-obese subjects (20
      men and 23 women) with the mean age of 25.8 + SD 5.3 y for men and 23.9 + SD 1.9
      y for women and their mean BMI was 23.1 +/- 1.4 for men and 23.0 +/- 1.8 for
      women. Serum leptin was significantly higher in women 8.8 + SEM 2.10 than men 2.2
      + SEM 0.26 ng /ml.Also included were 46 obese subjects (25 men and 21 women) with
      a mean age of 29.4 + SD 7.6 y for men and 28.8 + SD 6.2 y for women and a mean
      BMI of 35.5 +/- 5.7 for men and 35.6 +/- 4.4 for women. Serum leptin was
      significantly higher in women 23.0 + SEM 3.98, than men 12.5 + SEM 2.24 ng /ml.
      Serum leptin was significantly higher in obese men and women compared to non
      obese subjects. Serum leptin significantly, and positively correlated with BMI (r
      0.440), hip circumference (r 0.425), serum insulin (r 0.334), and HOMA IR (r
      0.334).There was no correlation with mean age, mean systolic BP, mean diastolic
      BP, or WHR. CONCLUSIONS: Serum leptin increased with obesity, and was higher in
      women than men, both lean and obese. Serum leptin correlated positively with BMI
      and hip circumference. Though, correlation between leptin and insulin resistance
      was found, they probably reflect two different metabolic compartments.

PMID- 23012128
TI  - The effect of age, obesity and parity on blood pressure and hypertension in non
      pregnant married women.
AB  - OBJECTIVE: To assess the effect of age, body mass index (BMI) and parity on
      systolic and diastolic blood pressures (BPs) and hypertension. SUBJECTS AND
      METHODS: A cross-sectional prospective study of 441 non-pregnant married women
      ranging in age from 15-60 years. For each woman selected, a detailed
      questionnaire dealing with sociodemographic profile including reproductive data
      was completed. Systolic and 5(th) phase diastolic BPs were measured using a
      standard mercury sphygmomanometer. Body weight and height were measured using an
      Avery Beam weighing scale and a stadiometer respectively. RESULTS: In this study
      sample, the overall prevalence of hypertension was 4.3%. Statistical analysis
      showed that age and BMI were positively and significantly associated with BPs
      (p<0.0001 for systolic BP & <0.002 for diastolic BP and p<0.0001 for systolic BP
      & <0.005 for diastolic BP respectively) and positively and significantly
      (p<0.0001 & <0.003 respectively) associated with an increase in the risk of
      hypertension (Odds ratio, 95% confidence interval: 1.53 (1.1-1.2) and 1.11 (1.04
      1.19) respectively) while parity was negatively and insignificantly associated
      with BPs (p<0.4 and <0.1 for systolic and diastolic BPs respectively) and
      negatively and insignificantly (P<0.1) associated with an increase in the risk of
      hypertension (Odds ratio, 95% confidence interval: 0.87 (0.74-1.03). CONCLUSION:
      Age and BMI were significant contributors to BPs and hypertension rather than
      parity. The negative association between parity and hypertension, although
      insignificant, implies that nulliparity rather than multiparity imposed an
      important effect on hypertension.

PMID- 23012129
TI  - Attitude and practice towards road traffic regulations among students of health
      sciences college in aseer region.
AB  - OBJECTIVE: The objectives of this study were to assess the knowledge, attitudes
      and practices of male students at the Health Science College in Abha, towards
      road traffic regulations. MATERIAL AND METHODS: This study was carried out during
      the second semester of the academic year 2002G among the students studying at the
      Health Science College for Boys in Abha, Aseer Region, Saudi Arabia. A
      questionnaire of 28 different questions was distributed to all available students
      and responded to under the direct supervision of the heads of the six departments
      of the college. The questionnaire consisted of three main parts; the first was
      about the socio-demographic and scientific data of the students; the second on
      the knowledge of road traffic regulations and the third dealt with attitudes and
      practice of driving and the use of seat belts. RESULTS: Two hundred thirty eight
      out of 297 students (80%) responded to the questionnaire in this study. The mean
      age of the participants was 21 years, 47% lived in cities, 70% and 72% had cars
      and driving licenses respectively. More than half of the students had been
      involved in road traffic accidents (RTAs), 22% of these had been injured in these
      RTAs and 13% admitted to hospital for an average of nine days. High speed was the
      main cause of their RTAs. The mean speed at which the students drove their cars
      within and outside the city boundaries were 81 KM/h and 127 KM/h respectively.
      The degree of knowledge of road traffic regulation was moderate to high in more
      than 75% of the students, while more than 90% of them believed in the importance
      of the use of seat belts. More than 75% of the participants mentioned that they
      had problems with the use of seat belts, the most common of which were
      forgetfulness and anxiety. CONCLUSION: This study revealed that many students had
      been involved in RTAs as a result of driving at high speed. Most of the students
      had good attitudes towards the use of seat belts. The rate of compliance to the
      use of seat belts increased with the legislation on its use. Continuing health
      education and the monitoring of compliance to road traffic regulations is
      necessary if the incidence of RTAs is to be reduced.

PMID- 23012130
TI  - Breast cancer awareness campaign: will it make a difference?
AB  - OBJECTIVE: The increased prevalence of breast cancer in recent years
      characterized by young age and delayed presentation has alerted women to randomly
      seek medical advice randomly. Breast cancer awareness programs are scarce and
      when available function on a very limited scale. In an attempt to increase cancer
      awareness among women, school teachers were targeted as missionaries to the
      community. The purpose of this study was to assess the efficiency of the breast
      cancer awareness campaign mounted by the author. MATERIAL AND METHODS: This
      survey was undertaken in 2005 with school teachers in Al Khobar district, Eastern
      Province of Saudi Arabia as the target. A breast cancer campaign was designed
      with lectures and workshops and delivered to school teachers in seven separate
      sessions. Each session was attended by 100-150 female teachers selected by their
      administration. Pre and post workshop questionnaires were distributed to assess
      knowledge of cancer symptoms, risk factors, attitudes towards breast self
      examination (BSE), mammography, and common misconceptions. RESULTS: The majority
      demonstrated minimal basic background knowledge on breast cancer, methods of
      conducting BSE or the need for mammography. The pre workshop questionnaires
      showed that 5% agreed and performed BSE, 14% thought that mammography may be
      needed, while 81% did not think any of these modalities were necessary. Post
      workshop questionnaire demonstrated positive results, 45% agreed to perform BSE,
      45% agreed to the need of mammographic screening while 10% still did not see the
      necessity of these procedures and refused the knowledge or the search for
      asymptomatic lesions. CONCLUSION: In order to succeed, breast cancer programs
      should be structured and implemented on a wide scale preferably tailored to fit
      individual communities. School teachers as educators help to convey the message
      to a large sector of the population by enhancing the knowledge of the younger
      generation on the necessity and the importance of early detection of cancer.

PMID- 23012131
TI  - Factors affecting the choice of health specialty by medical graduates.
AB  - A specialty is the transition from the undifferentiated medical graduate phase to
      the final, fully-differentiated specialist who is almost restricted to one
      specialized area of medical work. The medical specialty chosen by the medical
      practitioner is important for both the practitioner and the society. It is an
      important determinant of the future supply of doctors in different specialties
      and the planning of the workforce for the health-care services.Many factors
      influence specialty choices of the medical student and medical practitioner.
      These range from individual characteristics to the features of the specialty
      itself, including specialty-related lifestyle.This article explores factors
      influencing specialty choices of medical students and young practitioners. The
      article also suggests some general and practical principles that junior doctors
      should follow in selecting a specialty to suit their personality bearing in mind
      the health needs of the society.

PMID- 23012132
TI  - Guidelines for the construction of multiple choice questions tests.
AB  - Multiple Choice Questions (MCQs) are generally recognized as the most widely
      applicable and useful type of objective test items. They could be used to measure
      the most important educational outcomes - knowledge, understanding, judgment and
      problem solving. The objective of this paper is to give guidelines for the
      construction of MCQs tests. This includes the construction of both "single best
      option" type, and "extended matching item" type. Some templates for use in the
      "single best option" type of questions are recommended.

PMID- 23012133
TI  - Intracranial volume, cranial thickness, and hyperostosis frontalis interna in the
      elderly.
AB  - OBJECTIVES: According to the "brain reserve hypothesis," a larger premorbid brain
      protects against the development of dementia. The aim of this study was to reveal
      a possible pathophysiology of brain degenerative diseases by studying
      intracranial bone lesions that act to reduce intracranial volume (ICV), such as
      hyperostosis frontalis interna (HFI). METHODS: Three hundred and eighty
      postmenopausal females (aged 60+) who had undergone a head computerized
      tomography scan (Brilliance 64, Philips Healthcare, Cleveland, OH) at the Carmel
      Medical Center, Haifa, Israel, before the study were included. The subjects were
      divided into four groups according to their degree of HFI. Six measurements of
      the skull and brain were taken. RESULTS: As HFI becomes more severe, the cranial
      bone thickness and cranial bone volume increase. This process is accompanied by a
      decrease in ICV. In none of the HFI groups studied there was a significant
      association between ICV and cranial bone thickness. The inter-relationships
      between the various thickness parameters are not disturbed by the degree of HFI.
      CONCLUSION: HFI is accompanied by an increase in thickness of all calvarial bones
      and reduced ICV. In addition, the thickening process initiated by HFI is
      synchronized among the calvarial bones. Presence of HFI suggests a decrease in
      brain volume and has a major clinical significance as it may indicate the
      beginning of degenerative processes of the brain. In addition, as females age,
      their skulls tend to develop more robust characteristics.

PMID- 23012134
TI  - Strophasterols A to D with an unprecedented steroid skeleton: from the mushroom
      Stropharia rugosoannulata.

PMID- 23012135
TI  - Twelve years experience with an innovative journal of family and community
      medicine: a self-assessment approach.

PMID- 23012136
TI  - Prevalence of herpes simplex virus types 1 and 2 and associated sociodemographic
      variables in pregnant women attending king fahd hospital of the university.
AB  - OBJECTIVES: The risk factors associated with herpes simplex virus (HSV)
      seropositivity in pregnant women in Saudi Arabia are not known. This study was
      aimed at identifying the sociodemographic variables associated with
      seroprevalence of HSV-1 and HSV-2 in pregnant women in a Saudi hospital.
      MATERIALS AND METHODS: This is a hospital-based cross-sectional study that
      included all pregnant mothers who delivered at King Fahd Hospital of the
      University (KFHU) over a period of two years (November 2002 to October 2004).
      Anti-HSV-1 and anti-HSV-2 IgG and IgM antibodies were determined using type
      specific ELISA. Each subject completed a structured questionnaire. Relevant
      sociodemographic variables were analyzed. RESULTS: A higher prevalence of HSV-1
      IgG antibodies (93.2%) was found in those mothers who were not educated
      (illiterate or read and write only) in comparison with pregnant women with formal
      school education (p = 0.021). This was confirmed by using multiple regression
      analysis (p = 0.027). The prevalence of HSV-2 IgG was higher among civil servants
      and teachers (40.0 % and 14.7 % respectively) than in unskilled labourers,
      professionals, or housewives (p = 0.0001). Using multiple regression analysis,
      the prevalence of HSV-2 IgG was found to increase in older mothers (p = 0.037).
      No statistically significant association was found between HSV seroprevalence and
      other socio demographic variables. CONCLUSIONS: Identifying the sociodemographic
      factors associated with HSV infection will help in understanding the epidemiology
      of HSV infection in Saudi women and may help in designing preventive measures.

PMID- 23012137
TI  - A study of maternal dietary intake during pregnancy in riyadh, saudi arabia.
AB  - OBJECTIVE: This study was carried out to evaluate the dietary nutrient intake of
      pregnant women. The relationship between dietary intake and pregnancy outcome was
      also studied. METHOD: A total of 114 pregnant women were studied, using
      systematic random sampling. RESULTS: THE PERCENTAGES OF THE MEAN NUTRIENT INTAKE
      BELOW THE RECOMMENDED DIETARY ALLOWANCES (RDA) FOR PREGNANT WOMEN WERE AS THE
      FOLLOWS: 51.8%, 93.9%, 82.5% and 98.2% for energy, vitamin B1, calcium and iron,
      respectively. Moreover, 13.2% of the women experienced some form of pica. Using
      height and mid-arm circumferences, about 2.8% and 4.4% were seen to be
      undernourished respectively. CONCLUSION: Saudi pregnant women need guidance in
      selecting nutrient dense foods to reduce maternal and outcome health hazards.

PMID- 23012139
TI  - Erectile dysfunction among diabetic patients in saudi arabia: a hospital-based
      primary care study.
AB  - OBJECTIVES: The aim of the present study was to estimate the prevalence of
      erectile dysfunction in men with diabetes mellitus attending a primary care
      clinic in King Khalid University Hospital, Riyadh, Saudi Arabia. METHODS: A cross
      sectional study was carried out on men with diabetes mellitus followed in a
      primary care clinic of King Khalid University Hospital in Riyadh, Saudi Arabia,
      from 13 November 2005 to 13 June 2006. A total of 186 diabetic patients were
      interviewed. Data collection forms were completed by a member of the medical
      staff, a family medicine consultant, during the consultation of diabetic patients
      in the primary care clinic. Erectile dysfunction was categorized as absent
      erectile dysfunction (normal function), partial erectile dysfunction, and
      complete erectile dysfunction. The data was analyzed using the Statistical
      Package of Social Science (SPSS) version 11.5. A p-value of less than 0.05 was
      considered statistically significant. RESULTS: A total of 186 men with diabetes
      mellitus were interviewed during the study period. The majority of diabetic
      patients (95%) had type 2 diabetes. Most of the patients (68.8%) were on oral
      hypoglycemic agents, 24.7% on insulin injection, and 6.5% on diet only. The
      present study showed that 11.2% of the diabetic patients were suffering from
      complete and severe erectile dysfunction, while 64% of the patients complained of
      partial erectile dysfunction which was affecting their marital relationship. The
      cardiovascular risk factors in the 186 diabetic patients were hypertension 34.9%,
      smoking 13.4%, obesity 40%, and dyslipidemia 16.6%. CONCLUSIONS: Complete
      (severe) and partial erectile dysfunction was quite common among adult diabetic
      patients in a hospital-based primary care setting in Saudi Arabia. It is
      important for primary care physicians to diagnose erectile dysfunction in
      diabetic patients, and to counsel them early, as most patients are hesitant to
      discuss their concern during a consultation. Further studies are recommended to
      evaluate the effect of other risk factors on erectile dysfunction in diabetic
      patients.

PMID- 23012138
TI  - Prevalence of antibodies to human parvovirus b19 in saudi women of childbearing
      age in makkah.
AB  - OBJECTIVES: To determine the seroprevalence rate of immunoglobulin G (IgG) and
      immunoglobulin M (IgM) to parvovirus B19 in pregnant Saudi women in Makkah.
      SUBJECTS AND METHODS: Using enzyme-linked immunosorbent assay (ELISA), a total of
      1200 serum samples were tested for antibodies to parvovirus B19 known to cause a
      variety of clinical syndromes in women and newborn infants. RESULTS: Parvovirus
      B19 IgG antibodies detected in 46.6% and IgM antibodies were found in 2.25% of
      different age groups. CONCLUSION: The previous exposure to parvovirus B19 was
      determined, and 560 (46.6%) of 1200 pregnant Saudi women tested at their first
      antenatal visit were seropositive for specific IgG. The rate of maternal
      infection in susceptible pregnancies was 2.25%. These results were in accordance
      with previous studies performed in other countries.

PMID- 23012140
TI  - Care-seeking behavior for Fever in children under five years in an urban area in
      eastern Sudan.
AB  - BACKGROUND: Early diagnosis and prompt treatment are the basic elements of
      malaria control. The mother's perceptions about the cause of the fever, duration
      of sickness, accessibility and the anticipated cost of treatment, frequent use of
      traditional medicine, and judgement of the severity of the fever are the most
      important determinants for effective treatment of fever in children. SUBJECTS AND
      METHODS: This cross-sectional study was conducted in Kassala city, in Eastern
      Sudan to investigate the caregivers' care-seeking behaviour related to fever
      among children < 5 years. Data was collected by trained social workers using a
      structured questionnaire and was analysed by means of SPSS. RESULTS: Three
      hundred fifty housewives were interviewed. The majority (85.7%) had had at least
      basic education and 244 (69.7%) were full-time housewives. A total of 237 (67.7%)
      mothers were found to have adequate knowledge about malaria. Malaria was
      perceived by only 143 (40.9%) of the respondents as a cause of low grade fever
      and this percentage was almost doubled in the case of high fever. There were
      similar findings with respect to the selection of treatment sources and the use
      of antimalarial drugs. High fever urged 319 (91.1%) to seek advice from health
      workers and 281 (80.3%) to take drugs other than chloroquine. CONCLUSION: The
      intensity of fever (low/ high) governed the respondent's perceived causes of
      fever, decision about available treatment options and the type of antimalarial
      drugs they used. Health education programmes should focus on the importance of
      seeking early advice, compliance with prescribed treatment and awareness and
      handling of danger signs before presenting at health facility.

PMID- 23012141
TI  - An outbreak of foodborne diarrheal illness among soldiers in mina during hajj:
      the role of consumer food handling behaviors.
AB  - OBJECTIVE: An investigation of the outbreak was initiated as a result of the
      number of cases of gastroenteritis reporting to a general hospital in Mina during
      the pilgrimage to Makkah (HAJJ). This study was conducted to identify the source
      of the outbreak, assess its extent, and make recommendations to prevent similar
      outbreaks in the future. METHODOLOGY: A case was defined as any individual who
      developed diarrhea with or without abdominal pain after eating at the camp in
      Mina on 3(rd) January 2006. A retrospective cohort study was conducted to
      identify food items and circumstances responsible for this outbreak. Laboratory
      tests included stool cultures of all diarrhea patients, and rectal swabs from all
      food handlers were cultured for enteric pathogens. RESULTS: A total of 50 Saudi
      Male Soldiers were interviewed. Out of these, 16 (39%) had developed
      gastroenteritis, most commonly manifested by diarrhea (100%), and abdominal colic
      (87.5%). The mean incubation period was 12.6 +/- 4.9 hours and the epidemic curve
      suggested a common point source outbreak. Out of three served meals, lunch was
      found to have a statistically significant association with illness (p=0.0230).
      Out of five food items served, rice was the only food item found to have a
      statistically significant association with illness (p=0.0230). No food remnants
      were found for sampling. All results of stool cultures of all diarrhea patients,
      and rectal swabs from all food handlers were inconclusive. CONCLUSIONS: This
      outbreak was most likely caused by eating contaminated rice served at lunch on
      3(rd) January. The most likely organisms were Bacillus cereus, and/or Clostridium
      perfringens. Consuming food that was kept at an unsafe temperature wihout being
      reheated was the most probable important factor leading to this outbreak.

PMID- 23012142
TI  - Morbidity patterns among king faisal university students, Al hassa, kingdom of
      saudi arabia.
AB  - OBJECTIVES: To explore the prevalent morbidity problems among students at King
      Faisal University. To identify the nature of referred cases and assess the
      efficiency of the referral system. SUBJECTS AND METHODS: This was a
      retrospective, records-based descriptive study, involving the examination of the
      health records of students at King Faisal University, who attended the Medical
      Center for Primary Health Care services in a five-year period. A pre-tested
      compilation sheet was used for data collection. RESULTS: Out of 2472
      consultations, about 58 % of the diagnosed morbidity conditions were of
      infectious nature, mostly affecting the respiratory (62%), dental (14%),
      gastrointestinal (7%), and skin infections (5 %), with more prevalence among
      males. The non-infectious morbidity conditions were recorded more among females
      and included muscle and joints problems (16 %), allergic conditions (15 %),
      gastrointestinal (8 %), and trauma (5 %). Some of the encountered morbidity
      demonstrated seasonal variation. Case referrals were about 6 %, more in the non
      infectious conditions, with a deficient feedback system. CONCLUSION: Quality
      improvement of the medical records and the establishment of a proper referral
      system are necessary. Health education on preventable morbid conditions should be
      organized and implemented.

PMID- 23012143
TI  - Pyrene-based Y-shaped solid-state blue emitters: synthesis, characterization, and
      photoluminescence.
AB  - A series of pyrene-based Y-shaped blue emitters, namely, 7-tert-butyl-1,3
      diarylpyrenes 4 were synthesized by the Suzuki cross-coupling reaction of 7-tert
      butyl-1,3-dibromopyrene with a variety of p-substituted phenylboronic acids in
      good to excellent yields. These compounds were fully characterized by X-ray
      crystallography, UV/Vis absorption and fluorescence spectroscopy, DFT
      calculations, thermogravimetric analysis, and differential scanning calorimetry.
      Single-crystal X-ray analysis revealed that the Y-shaped arylpyrenes exhibited a
      low degree of pi stacking owing to the steric effect of the bulky tert-butyl
      group in the pyrene ring at the 7-position, and thus, the intermolecular pi-pi
      interactions were effectively suppressed in the solid state. Despite the
      significantly twisted nonplanar structures, these molecules still displayed
      efficient intramolecular charge-transfer emissions with clear solvatochromic
      shifts on increasing solvent polarity. An intriguing fact is that all of these
      molecules show highly blue emissions with excellent quantum yields in the solid
      state. Additionally, the two compounds containing the strongest electron
      accepting groups, CN (4 d) and CHO (4 f), possess high thermal stability, which,
      together with their excellent solid-state fluorescence efficiency, makes them
      promising potential blue emitters in organic light-emitting device applications.

PMID- 23012144
TI  - Health manpower in saudi arabia: which way forward?

PMID- 23012145
TI  - Thunderstorm-associated bronchial asthma: a forgotten but very present epidemic.
AB  - Acute episodes of bronchial asthma are associated with specific etiological
      factors such as air pollutants and meteorological conditions including
      thunderstorms. Evidence suggests that thunderstorm-associated asthma (TAA) may be
      a distinct subset of asthmatics, and, epidemics have been reported, but none from
      Saudi Arabia.The trigger for this review was the TAA epidemic in November 2002,
      Eastern Saudi Arabia. The bulk of patients were seen in the King Fahd Hospital of
      the University, Al-Khobar. The steady influx of acute cases were managed
      effectively and involved all neighboring hospitals, without evoking any "Major
      Incident Plan".THREE GROUPS OF FACTORS ARE IMPLICATED AS CAUSES OF TAA:
      pollutants (aerobiologic or chemical) and meteorological conditions.
      Aerobiological pollutants include air-borne allergens: pollen and spores of
      molds. Their asthma-inducing effect is augmented during thunderstorms.Chemical
      pollutants include greenhouse gases, heavy metals, ozone, nitrogen dioxide,
      sulfur dioxide, fumes from engines and particulate matter. Their relation to rain
      associated asthma is mediated by sulfuric and nitric acid.Outbreaks of non
      epidemic asthma are associated with high rainfall, drop in maximum air
      temperature and pressure, lightning strikes and increased humidity. Thunderstorm
      can cause all of these and it seems to be related to the onset of asthma
      epidemic.Patients in epidemics of TAA are usually young atopic adults not on
      prophylaxis steroid inhalers. The epidemic is usually their first known attack.
      These features are consistent with the hypothesis that TAA is related to both
      aero-allergens and weather effects. Subjects allergic to pollen who are in the
      path of thunderstorm can inhale air loaded with pollen allergen and so have acute
      asthmatic response. TAA runs a benign courseDoctors should be aware of this
      phenomenon and the potential outbreak of asthma during heavy rains. A & E
      departments and ICU should be alert for possible rush of asthmatic admissions and
      reinforce ventilators and requirements of cardio-pulmonary resuscitation.
      Scientific approach should be adopted to investigate such outbreaks in the future
      and must include meteorological, bio-aerosole pollutants and chemical pollutant
      assessment. Regional team work is mandatory.

PMID- 23012146
TI  - The approach to a patient with a bleeding disorder: for the primary care
      physician.
AB  - Normal Hemostasis requires the interaction of platelets and the clotting cascade
      with normal blood vessels and supporting tissues. Bleeding problems and easy
      bruising are commonly encountered clinical problems. Assessment of these patients
      is a multistep evaluation process that involves a complete detailed history,
      thorough physical examination and relevant laboratory evaluation. Many disorders
      are usually relatively straight forward to diagnose, but in other disorders,
      patients may have "hidden" signs and symptoms making diagnosis more difficult. A
      meticulous approach must be used to plan the first steps of management.

PMID- 23012147
TI  - Medicine and clinical skills laboratories.
AB  - The main objective of the medical curriculum is to provide medical students with
      knowledge, skills and attitudes required for their practice. A decade ago, the UK
      Medical Council issued a report called "Tomorrow's Doctors"(1) which called for
      the reduction in the factual content of the medical course with the promotion of
      problem-based and self-dedicated learning. This report was the basis for a move
      toward an extensive reform of the medical and nursing curricula. The new reformed
      curricula enhanced the integrated medical teaching and emphasized the teaching
      and learning of clinical skills. However, there were still concerns about the
      standards and appropriateness of the skills of new medical graduates.(2)The
      changes in the teaching and learning methods, the radical changes in the health
      care delivery and the rapid growth of technology challenged the traditional way
      of clinical skills development and led to the emergence of clinical skills
      laboratories (CSLs) in the medical education of many medical and nursing schools.
      With the proliferation of the CSLs, it is important to evaluate and introduce the
      reader to their applications, bearing in mind the paucity of information on this
      subject particularly over the last couple of years. This article is based on
      literature review.

PMID- 23012148
TI  - Level and determinants of infant and under-five mortality in wad-medani town,
      Sudan.
AB  - AIM: This study aimed to determine the level of infant and under-five mortality
      rates and to examine the effect of socioeconomic, demographic and environmental
      factors on the health status of the children under five years. METHODS: The data
      for this study were collected by means of a questionnaire addressed to women in
      Wad-Medani, Sudan. Three hundred women in the reproductive age (15-49) years were
      chosen randomly for this study. The data were analyzed statistically using the
      Statistical Package for Social Sciences (SPSS). Frequency distributions and a
      statistical test based on Chi-square for independence was conducted. RESULTS:
      Infant mortality rate was 77 per 100 and child mortality rate was 67 per 100. The
      results revealed that immunization, child order, child birth weight, birth
      interval and contraceptive use had a significant influence on the mortality of
      children under the age of five. The mother's level of education is highly
      significant on the mortality of children under five years old. CONCLUSIONS: The
      Ministry of Health should give greater attention to improving immunization
      services and concentrate on health education campaigns for mothers and for the
      community.

PMID- 23012149
TI  - The relationship of body weight to altitude in preschool children of southwestern
      saudi arabia.
AB  - OBJECTIVES: To determine the average weight and height and the prevalence of
      overweight or obesity and thinness in preschool children of the Southwestern
      highlands of the Kingdom of Saudi Arabia and compare them with their counterparts
      living at lower altitudes. METHODS: A cross-sectional study of 559 preschool
      children aged 12-71 months born and living permanently at high altitude, and 463
      preschool children of comparable age born and living permanently at low altitude.
      For each child at high and low altitude, age was recorded and weight and height
      were measured. Weight for height Z-score with WHO standards was used for an
      assessment of normal weight, overweight or obesity and thinness. RESULTS: The
      highland preschool children were found to be significantly heavier and taller
      than their counterparts living at low altitude. 92.1% of all highland preschool
      children and 67.6% of lowland preschool children were found to have normal weight
      (p < 0.0001). Overweight or obesity was insignificantly greater among preschool
      children of the highlands (2.3%) compared to the preschool children of the low
      lying areas (0.9%) (p<0.7). Thinness was significantly more prevalent among
      preschool children of the lowlands (31.5%) than preschool children of the
      highlands(5.5%) (p< 0.0001). At both high and low altitude, there were no
      significant differences in the prevalence of overweight or obesity and thinness
      between boys and girls. CONCLUSION: The findings of this study indicate that
      thinness is a major nutritional problem among lowland preschool children. This
      may be attributed to the prevailing tropical environmental conditions on the
      health of children at low altitude.

PMID- 23012150
TI  - Clinico-epidemiological features of hypertensive subjects in kassala town,
      eastern Sudan.
AB  - OBJECTIVES: To study the clinico- epidemiological profile of hypertension in a
      series of hypertensive patients in a town in Eastern Sudan. METHODS: A sample of
      242 hypertensive patients was studied using a structured questionnaire including
      the clinico-epidemiological features associated with hypertension. RESULTS: Two
      thirds of the sample were females, 73.6% of whom were in the 35-64 year age
      range; three-quarters of them had a low level of education. Significant risk
      factors for hypertension included positive family history of hypertension, and
      being from the Northern Sudan. Significantly more patients from the eastern and
      western regions had coronary heart disease (P<0.001). Also, significantly more
      patients from Western Sudan had left ventricular failure (P<0.02) and congestive
      heart failure (p<0.0001), while significantly more patients from Southern Sudan
      had nephropathy (P<0.007). CONCLUSIONS: The study reveals some clinico
      epidemiological characteristics in a series of hypertensive patients in Eastern
      Sudan. It suggests a low rate of blood pressure control as well as ethnic
      variation of blood pressure control and complications.

PMID- 23012152
TI  - Public health schools in saudi arabia: a necessity or a luxury?

PMID- 23012151
TI  - Students' views on student-teacher relationship: a questionnaire-based study.
AB  - AIM: The aim of this study is to assess students' views on student-teacher
      relationship and its effect on academic grades. METHODS: The present cross
      sectional study was conducted in the College of Medicine, King Saud University,
      Riyadh, in 2005. The questionnaires were distributed to 420 students during the
      examination period in order to obtain a full response. It consisted of items on
      different aspects of student-teacher relationship for which the responses were
      measured on a 4-point scale. The response rate was about 83%. RESULTS: The
      current relationship between the student and the teacher was evaluated as very
      good and good by 61% of the study sample. The responses were associated with
      their grades as (X(2)=6.25, p=0.012). Eighty-four point one percent of students
      with higher and above average grades felt that expulsion from class was an
      appropriate means of controlling the class. Also (78.2%) students felt that the
      teachers treated them with respect, and their responses were significantly
      associated with their grades (X(2)=11.8, p=0.003). Eight-four percent of the
      students with higher and above average grades strongly agreed that teacher's
      performance was affected by students' attendance or absence and the responses
      were significantly associated with their grades (X(2)=4.35, p=0.037). The
      responses to most of the items by the students were independent of their grades.
      CONCLUSION: This study concludes that student-teacher relationship was good in a
      medical school and the views of students on this relationship were independent
      with their academic grades. Further study which includes from 1(st) year to 5th
      year undergraduate students is required to give a broader view of student-teacher
      relationship in a medical school.

PMID- 23012153
TI  - A community-based screening campaign for the detection of diabetes mellitus and
      hypertension in the eastern province, saudi arabia: methods and participation
      rates.
AB  - OBJECTIVE: To describe a community-based diabetes and hypertension screening
      campaign, the percentage of screened positive individuals, identified the
      participation rate, and the factors affecting the participation.  CAMPAIGN DESIGN
      AND METHODS: A community-based screening campaign whose main objective was the
      screening for diabetes and hypertension was conducted in the Eastern Province of
      Saudi Arabia for three and half months in the year 2004. A structured
      questionnaire was used. Diabetes mellitus was diagnosed on the basis of repeated
      detection of a fasting blood sugar equal to or more than 126 mg/dl, and
      hypertension when the blood pressure was 140/90 mm Hg or more. RESULTS: Of the
      650,000 target population, 214,381 (33%) participated, and 197,681 questionnaire
      were completed. Of the number of individuals screened, 31,711 (16%) were positive
      for abnormal blood pressure and /or glucose, and needed confirmation of their
      results. Only 17296 (54.5%) of them were referred to health facilities for
      confirmation of results CONCLUSION: Community screening campaigns for diabetes
      mellitus and hypertension is extremely efficient in identifying undiagnosed
      diabetic and hypertensive individuals. The most successful strategy for the
      screening and confirmation of results was through PHCCs, especially in the rural
      areas, where there was good organization and strict adherence to guidelines on
      methodology.

PMID- 23012154
TI  - Appointment system in primary care: opinion of consumers and providers.
AB  - BACKGROUND: The appointment system in primary care is widely used in developed
      countries, but there seems to be a problem with its use in Saudi Arabia.
      OBJECTIVES: (1) To explore opinions and satisfaction of consumers and providers
      of care in Primary Health Care regarding walk-in and the introduction of the
      appointment system. (2) To examine factors which may affect commitment to an
      appointment system in PHC. SUBJECT AND METHOD: Two hundred sixty (260) consumers
      above the age of 15 years as well as seventy (70) members of staff were randomly
      selected from 10 Primary Health Care Clinics in the National Guard Housing Area,
      Riyadh and asked to complete a structured questionnaire designed to meet the
      study's objectives. RESULTS: The majority of consumers and providers of care were
      in favour of introducing appointments despite their satisfaction with the
      existing walk-in sysem. Respondents saw many advantages in the appointment system
      in PHC such as time saving, reduction of crowds in the clinics and guarantee of a
      time slot. The main perceived disadvantage was the limitation of accessibility to
      patients especially with acute conditions. The main organizational advantages and
      disadvantages perceived by providers were related to follow-ups of chronic
      patients, no shows and late arrivals. The majority of the patients preferred
      appointments in the afternoon and the possibility of obtaining an appointment
      over the telephone. CONCLUSION: In this study, both consumers and providers
      supportted the idea of introducing the appointment mixed system in primary care,
      but further study is required.

PMID- 23012155
TI  - Determinants of birth spacing among saudi women.
AB  - BACKGROUND: High fertility levels are of major concern to planners and policy
      makers in most countries in the developing world. In Saudi Arabia, the rate of
      population growth is the third highest of the countries of the Eastern
      Mediterranean Region. OBJECTIVES: This study aimed at identifying determinants of
      birth spacing and attitudes toward family planning among Saudi women. METHODS: A
      cross sectional survey of all women who have been married before, aged 15-49
      years attending Al Hada armed forces hospital (primary health care and antenatal
      care clinics), was conducted between 1(st) February 2005 and 31(st) January 2006.
      Data was collected on socio-demographic, biological characteristics, beliefs,
      attitudes, and utilization of family planning services, pregnancy intervals and
      medical history RESULTS: For the 786 women included in the study, the mean
      duration of interbirth interval was 2.38+/-1.24 years. The multivariate Cox
      regression revealed that a woman's education, work status, husband's work status,
      a woman's history of chronic diseases, and husband's encouragement of interbirth
      spacing were the only significant predictors of longer interbirth intervals.
      Shorter interbirth intervals were independently predicted by lower family income,
      and presence of female offspring only or equal number of male and female
      offspring as opposed to presence of more males. The great majority of
      participating women (98%) had a positive opinion of the effect of birth spacing
      on the family. CONCLUSION: This study showed that certain factors were
      significant predictors of interbirth spacing for the Saudi women. This should
      lead to the encouragement of longer intervals between births. However, further
      studies are needed to ascertain a cause-effect association.

PMID- 23012156
TI  - Quality of primary care referral letters and feedback reports in buraidah, qassim
      region, saudi arabia.
AB  - OBJECTIVE: To evaluate the quality of referral letters and feedback reports
      written according to the standards of Quality Assurance Manual of Ministry of
      Health from primary health care centers (PHCC's) in Buraidah. METHODOLOGY: This
      study was conducted during October and November 2004. A total of 330 referral
      letters and feedback reports were randomly selected from six PHCCs (20% from
      PHCCs in Buraidah City). About 55 referral and feedback letters were selected
      from each PHCC by systematic sampling method. The referral letters and feedback
      reports were reviewed thoroughly for the main items required in ideal referral
      letters and feedback reports according to the standard of Quality Assurance
      Manual of Ministry of Health, and a scoring system was used RESULT: Many of the
      referral letters lacked such important information as the history in 36%, vital
      signs in 30%, results of clinical examination in 45%, results of basic
      investigations in 52%, provisional diagnosis in 50%, and treatment given in PHCCs
      in 47%. The legibility of referral letters and feedback reports was good in 75%,
      and 63% respectively, and the quality of referral letters and feedback reports
      was good in 63% and 39% respectively. The rate of feedback reports received by
      PHCCs was 30% of total number of referrals to the hospitals. The referral rate
      was (4%) from total number of patients seen in PHCCs. The most frequent reasons
      for referrals were for general treatment 36.7%, for general diagnostic evaluation
      28%, and for laboratory investigation 18.8%. CONCLUSION: The referral rate from
      PHCCs in Buraidah fell within the standard set in Quality Assurance Manual.
      However, the quality of referral letters and feedback reports was poor in 17.6%
      and 29.7% respectively. The quality of both referral letters and feedback reports
      should improve to guarantee the quality of patient care..

PMID- 23012157
TI  - Effects of dietary flavonoids intake in saudi patients with coronary heart
      disease.
AB  - OBJECTIVES: The aim of the study was to assess the dietary intake of flavonoids
      and their effect on serum lipid levels in Saudi patients with coronary heart
      disease (CHD). METHODOLOGY: A cross-sectional study with a sample of 50 CHD
      patients and 50 controls. A 24-hour recall method was used to collect data on the
      dietary intake of macronutrients, flavonoids, and antioxidant vitamins. A food
      frequency questionnaire (FFQ) was used to collect data on habitual consumption
      during the year preceding the interview. Baseline data collection included
      medical history, anthropometric measurements, physical activity, and smoking
      status. RESULTS: CHD patients showed significantly less intake of fruits and
      vegetables compared to the controls. Serum lipids including total cholesterol
      (TC), triglycerides (TG), and low density lipoproteins (LDL) were found to be
      significantly higher in CHD patients than in the controls. The main sources of
      flavonoids in a typical Saudi diet are tea, fruits (apples), vegetables (onions),
      and chocolate. The intake of flavonoids and antioxidant vitamins was
      significantly lower in CHD patients compared to the controls. A negative
      correlation between the dietary intake of different flavonoids and serum LDL was
      observed in CHD patients. Significant correlation was found between the intake of
      flavonol and waist to hip ratio CONCLUSIONS: The findings of the study support a
      potential protective effect of dietary flavonoids in relation to CHD. The study
      showed that consuming more Flavonoids may have positive effect on lowering blood
      lipids.

PMID- 23012158
TI  - Developing an integrated organ/system curriculum with community-orientation for a
      new medical college in jazan, saudi arabia.
AB  - BACKGROUND: Jazan province is located in the south-west of the Kingdom of Saudi
      Arabia. The province is offlicted with a wide spectrum of diseases and therefore
      have a special need for more health services. The Faculty of Medicine at Jazan
      has been following the traditional curriculum since its inception in 2001. The
      traditional curriculum has been criticized because of the students inability to
      relate what they learned in the basic sciences to medicine, thus stifling their
      motivation. It was felt that much of what was presented in preclinical courses
      was irrelevant to what the doctor really needed to know for his practice. The
      College therefore, decided to change to an integrated curriculum. DESIGN: The
      study was conducted in 2004-2005 in the Faculty of Medicine, Jazan University. It
      began with a literature survey/search for relevant information and a series of
      meetings with experts from various institutions. A Curriculum Committee was
      formed and a set of guiding principles was prepared to help develop the new
      curriculum. A standard curriculum writing format was adopted for each module. It
      was decided that an independent evaluation of the new curriculum was to be done
      by experts in medical education before submission for official approval. There
      were several difficulties in the course of designing the curriculum, such as:
      provision of vertical integration, the lack of preparedness of faculty to teach
      an integrated curriculum, and difficulties inherent in setting a truly integrated
      examination. CURRICULUM: The program designed is for 6 years and in 3 phases; pre
      med (year 1), organ/system (years 2 and 3), and clinical clerkship (years 4, 5,
      and 6). This is to be followed by a year of Internship. The pre-med phase aims at
      improving the students' English language and prepare them for the succeeding
      phases. The organ/ system phase includes the integrated systems and the
      introductory modules. The curriculum includes elective modules, early clinical
      training, behavioral sciences, medical ethics, biostatistics, computer practice,
      and research methods. The curriculum provides active methods of instruction that
      include: small group discussion/ tutorials, problem-based learning (PBL), case
      study/ clinical presentations, seminars, skills practice (clinical skill lab),
      practical, demonstration, and student independent learning. Methods of evaluating
      students include continuous and summative assessment. CONCLUSION: The new
      curriculum adopted by the Jazan Faculty of Medicine is an integrated, organ/
      system based, community-oriented, with early clinical skills, elective modules,
      and innovative methods of instructions.

PMID- 23012159
TI  - Effect of a telephone-delivered coronary heart disease secondary prevention
      program (proactive heart) on quality of life and health behaviours: primary
      outcomes of a randomised controlled trial.
AB  - BACKGROUND: Participation in coronary heart disease secondary prevention programs
      is low. Innovative programs to meet this treatment gap are required. PURPOSE: To
      aim of this study is to describe the effectiveness of a telephone-delivered
      secondary prevention program for myocardial infarction patients. METHODS: Four
      hundred and thirty adult myocardial infarction patients in Brisbane, Australia
      were randomised to a 6-month secondary prevention program or usual care. Primary
      outcomes were health-related quality of life (Short Form-36) and physical
      activity (Active Australia Survey). RESULTS: Significant intervention effects
      were observed for health-related quality of life on the mental component summary
      score (p = 0.02), and the social functioning (p = 0.04) and role-emotional (p =
      0.03) subscales, compared with usual care. Intervention participants were also
      more likely to meet recommended levels of physical activity (p = 0.02), body mass
      index (p = 0.05), vegetable intake (p = 0.04) and alcohol consumption (p = 0.05).
      CONCLUSIONS: Telephone-delivered secondary prevention programs can significantly
      improve health outcomes and could meet the treatment gap for myocardial
      infarction patients.

PMID- 23012160
TI  - An integrated approach to a psychiatric perspective: a bio-psycho-social model.

PMID- 23012161
TI  - Health and socio-economic hazards associated with khat consumption.
AB  - The consumption of the stimulant leaf Khat (Catha edulis Forsk) is widespread in
      several countries of East Africa and the Arabian Peninsula. The leaf comes from a
      small evergreen shrub that can grow to the size of a tree. Young buds and tender
      leaves are chewed to attain a state of euphoria and stimulation. Khat leaves
      contain cathinones, an active brain stimulant that is similar in structure and
      pharmacological activity to amphetamines. Like amphetamines, Khat ingestion in
      low doses results in decreased appetite, euphoria, increased intellectual
      efficiency, and hyperalertness.High doses and chronic use of Khat can cause more
      serious adverse neurological, psychiatric, cardiovascular, dental,
      gastrointestinal and genitourinary effects. Besides damaging health, Khat has
      adverse socio-economic consequences effects on many other aspects of life
      including the loss of thousands of acres of arable land and billions of hours of
      work.The purpose of this review is to describe briefly the adverse consequences
      of habitual chewing of Khat on health, and help educate the general public. The
      study is based on literature review that includes internet search and journals.

PMID- 23012162
TI  - Health needs assessment.
AB  - THIS PAPER TAKES A PUBLIC HEALTH APPROACH TO BRIEFLY EXAMINE: (i) the concept of
      community health care need assessment; (ii) the roles of academic institutions in
      health needs assessment; (iii) Jazan study to address the health care needs in
      Jazan region, Saudi Arabia. The methods included an analysis of the literature,
      distillation of experience from the recently Jazan Health Need Assessment Survey,
      and WHO reports. The most important perceived health problems in Jazan region are
      shortage of health care providers, increased prevalence of communicable diseases
      and poor environmental health. The academic institutions, Ministry of Health and
      other health care institutions need to work together to look for innovative
      approaches, especially to increase the awareness of the society on public health
      issues, and give more support to increase national and regional funding for
      community based studies.The findings of the assessment of the health needs of
      Jazan presented in this review could be utilized as a baseline and reference
      information for policy formulation, subsequent planning and cost effective
      intervention programs. It could also be utilized for the curriculum development
      or review for a community oriented medical schools.

PMID- 23012163
TI  - Screening for psychosocial problems in children attending the pediatric clinic at
      king khalid university hospital (kkuh) in riyadh (ksa).
AB  - INTRODUCTION: Psychosocial problems are highly prevalent among children and
      adolescents. One approach to facilitating recognition and referral of these
      problems is to use parent-completed screening questionnaire as part of routine
      primary care. AIM AND METHODS: The purpose of this study was to determine the
      prevalence and type of psychosocial problems in a random sample of children
      attending the pediatric clinic at KKUH at the time of the study. A 2-part
      questionnaire was designed for the study. The first part contained basic
      biographic data in addition to items which reflect the socioeconomic status of
      the family. The second part of the questionnaire comprised the inventory, which
      is a modified version of the Pediatric Symptoms Checklist (PSC).The inventory
      consisted of 38 items classified into five categories. The total score of the
      inventory ranged from 0-114. RESULTS: Three-hundred-twelve questionnaires were
      completed. The average of the total score was only 22.3 out of 114. The lowest
      score was 0 and the highest 84. The average scores of behavioral symptoms (BS)
      were the highest (7.03 out of 27) while that of the learning problems (LP) was
      the lowest (1.5 out of 18). The average score for mood symptoms (MS) was 5.6 out
      of 24, that for personality characteristics (PC) was 4.5 out of 24 and that for
      somatic symptoms (SS) was 4.3 out of 24. CONCLUSION: This study revealed the
      feasibility of screening for behavioral problems of children in an outpatient
      setting. It is necessary to implement screening procedures for psycho-behavioral
      problems, and train pediatricians to screen children presenting at clinics.

PMID- 23012164
TI  - Prevalence of somatization and minor psychiatric morbidity in primary healthcare
      in saudi arabia: a preliminary study in asir region.
AB  - OBJECTIVE: To determine the prevalence of psychological disorders and
      somatization among primary care patients from a semi-urban area of the Kingdom of
      Saudi Arabia. DESIGN: Screening of consecutive patients with the 12-item and 28
      item versions of the General Health Questionnaires and assessments of physical
      symptoms associated with somatization, using the HSCL-12. Eight primary care
      health centres in Assir, Saudi Arabia. RESULTS: About half of the sample had one
      or more psychological disorders. The prevalence of somatization detected by the
      GHQ-28 was 16%. The prevalence of somatization indicated by GPs' identification
      of medically unexplained symptoms was 14%. Women displayed higher levels of
      somatization than men. CONCLUSION: This study reported prevalence of
      psychological disorders that was as high as found in the more modern areas of
      Saudi Arabia such as Riyadh. The view that individuals in less open areas are
      protected from psychological disorders associated with stress and lifestyle
      pressure seems to be unsubstantiated. The results highlight the potential value
      of screening for psychological disorders using such simple instruments as the
      GHQ.

PMID- 23012165
TI  - Parental attitudes toward the prescription of psychotropic medications for their
      children.
AB  - OBJECTIVE: To explore parental attitudes towards the prescription of psychotropic
      medication for their children. METHOD: A questionnaire built to collect socio
      demographic data of parents and their attitudes was distributed among parents.
      RESULTS: One thousand and ten questionnaires were filled by parents. Fathers who
      completed the questionnaire were double the number of mothers. Eight hundred and
      eighteen parents (84.3%) agreed to the dispensing psychotropic medication to
      their children if necessary. About 83.5% preferred to start with psychotherapy
      before trying medication. Fathers are more than twice likely than mothers to
      agree to the use of psychotropic drugs. Older parents more easily agreed to give
      their children psychotropic drugs. Parents who used psychotropic drug themselves
      were more likely to agree to the use of psychotropic drug by their children.
      Having a child with a psychiatric illness is the most significant factor in
      making parents accede to giving children psychotropic medication. Other factors
      such as pressure from schools and the side effects of drugs could also modify
      decision of parents. CONCLUSION: Although most parents agreed to give their
      children psychotropic drugs if necessary, they preferred to start with
      psychotherapy sessions before giving them the drugs. Fear and worries about such
      issues as side effects of drugs or addiction should be considered. Pressure from
      school should also be considered when deciding on drug therapy.

PMID- 23012166
TI  - Assessment of the accuracy of death certification at two referral hospitals.
AB  - BACKGROUND: Death certification is a vital source of information used in
      mortality statistics worldwide to assess the health of the general population.
      This study focuses on the consistency of information between the death reports
      and the clinical records (files) of deceased patients in two hospitals: the King
      Khalid University Hospital (KKUH) and King Fahad National Guard hospital (KFNGH)
      in Saudi Arabia. METHODS: A random sample of the records of 157 deceased
      patients' registered in 2002 in the two hospitals was retrospectively reviewed
      independently to determine the underlying cause of death and compare them with
      death reports. It was also to check the accuracy of the translation from English
      in to Arabic. RESULTS: It was found that the underlying cause of death was
      misdiagnosed in 80.3% of the death reports. When the two hospitals were compared,
      no significant difference was observed (p>0.05). In addition, 81.8% of the
      accurate (correct) death reports in both hospitals were of patients who had died
      of a malignant disease. However, the translation of the underlying cause of death
      in KFNGH was correct in 86.1% of the death reports, while in KKUH it was only
      25%, which is highly statistically significant (p<0.0001). CONCLUSION: With the
      limitation of studying only a small number of cases, these results indicate a
      discrepancy between the file and death reports in relation to the cause of death.
      Also, the translation of the cause of death was inconsistent in the two
      hospitals. Hence, there is a real need to adopt suitable measures to improve the
      quality of death certification.

PMID- 23012167
TI  - Prescription non-conformities in primary care settings: how useful are
      guidelines.
AB  - BACKGROUND: Apart from having a negative impact on work flow in practice,
      prescription errors may pose a threat to patient safety. Such errors have been
      reported in the pharmaceutical services in spite of the clear guidelines issued
      by the parent organization. OBJECTIVE: This study was to explore the degree of
      conformity to the prescribing guidelines at Primary Care level in the Saudi
      National Guard Health Affairs in Riyadh. METHODS: Prescriptions were collected
      during audits done fortnightly through a simple random selection from a sampling
      frame of all prescriptions given within the period. Information about each
      prescription was entered in a database by the pharmacists and each prescription
      was classified according to its conformity to the guidelines. Information was
      presented on 330 prescriptions for eleven audits carried out from September 2004
      to February 2005. RESULTS: 87% of the prescriptions did not conform to the given
      guidelines. Less than 1% of the inconsistencies were potentially harmful to the
      patient, 77.8% had possible negative effect on the pharmacist's work, while 21.3%
      were unimportant. Patient information was deficient in 16.9% of cases, drug
      information in 49.6% and archiving/record information related non-conformities
      constituted 33.5%. CONCLUSIONS: Conformity to prescribing guidelines is quite low
      in spite of the significant input of resources by the parent organization. This
      burden on work flow, utilization of time and service delivery needs to be studied
      and addressed by ensuring that there are periodic audits in the work routines of
      primary health care, and a feedback given to the care providers.

PMID- 23012168
TI  - Colorectal cancer: a case control study of dietary factors, king faisal
      specialist hospital and researh center, riyadh, saudi arabia.
AB  - OBJECTIVE: This study was designed to assess various dietary factors and the
      nutritional status of hospitalized patients with colorectal cancer. MATERIALS AND
      METHODS: A case-controlled study of fifty newly-admitted patients at King Faisal
      Specialist Hospital & Research Center, Riyadh, Saudi Arabia diagnosed with
      colorectal cancer were interviewed to collect data on various dietary factors and
      their nutritional status. Their data were compared with a sex-matched control
      group aged fifty. RESULTS: The consumption of meat high in fat, fried eggs and
      whole fat dairy products, and diet low in fibers 2-3 times or above per week
      increased the risk of colorectal cancer, while the consumption of whole wheat
      products, vegetables and fruits, and diet low in animal fats at the same rate per
      week may play a protective role against colorectal cancer in both men and women
      when compared to controls. CONCLUSIONS: The higher consumption of meat and fat
      from animal sources could increase the risk of colorectal cancer. The high
      consumption of whole wheat bread, fruits and vegetables with high fiber content
      could play a protective role against the risk of colorectal cancer in the Saudi
      society. Additional studies are needed in different regions of the Kingdom of
      Saudi Arabia to verify or refute these results.

PMID- 23012169
TI  - Preterm singleton breech delivery in a teaching hospital of saudi arabia: vaginal
      versus cesarean delivery.
AB  - OBJECTIVES: The aim of this study was to determine the incidence of singleton
      preterm breech babies born in a teaching hospital, and to study the influence of
      the mode of delivery on perinatal outcome in preterm births with breech
      presentation. METHODS: A retrospective analysis from the medical records of
      patients who had preterm singleton breech delivery (24 - 36 weeks gestation) was
      undertaken in a tertiary care hospital in the Eastern province of Saudi Arabia
      between January 1992 and December 2001. All the patients with intrauterine fetal
      death, multiple pregnancies and lethal congenital fetal malformations were
      excluded from the study. Intrapartum and neonatal morbidity and mortality in
      vaginal versus cesarean delivery groups were the main outcomes measured. RESULTS:
      Of 24,708 deliveries that occurred in the hospital during the period of study,
      there were 195 preterm singleton breech deliveries, giving an incidence of 0.08%.
      One hundred and forty-eight (75.9%) patients delivered vaginally and did not have
      any medical or obstetric complications. Forty-seven (24.1%) patients underwent
      caesarean section. While the neonatal morbidity was similar in the two groups,
      the neonatal mortality was significantly higher for vaginal delivery than
      cesarean section (p<0.00069). CONCLUSION: In view of the significantly higher
      neonatal mortality found in vaginal delivery, the present study favors abdominal
      delivery for a singleton preterm breech fetus.

PMID- 23012170
TI  - Assessment of pediatricians' need for training in child psychiatry.
AB  - BACKGROUND: Psychosocial problems are common health concerns in children.
      Therefore, it is essential for pediatricians to be able to identify psychiatric
      disorders. This depends on the knowledge, practice and attitudes towards
      psychiatric disorders in childhood. METHODS: A constructed questionnaire of items
      about knowledge, practice and attitudes of pediatricians toward psychiatric
      disorders in childhood was used. Four hundred and fifty questionnaires were
      distributed and collected from pediatricians in seven main governmental hospitals
      in Riyadh over a period of three months (between March 1 and May 30 2005).
      Findings were analyzed statistically. RESULTS: About 88.8% of the samples had not
      had any training in child psychiatry during their residency. Forty-eight percent
      were hesitant in diagnosing psychiatric disorders in children, 76.5% were not
      confident enough to treat these children, 48.5% were not confident enough to
      follow them up after being managed by a child psychiatrist and 49.9% were not
      confident to treat common side effects of psychotropic medications. About 88.8%
      of the pediatricians thought that pediatricians needed training in child
      psychiatry during pediatric residency programs. CONCLUSION: A significant number
      of pediatricians reported a lack of training in child psychiatry during residency
      programs. This has an adverse impact on their knowledge, attitudes and possibly
      practices in dealing with childhood psychiatric disorders.

PMID- 23012171
TI  - Knowledge of hepatitis B and vaccination status of some expatriate ethnic groups
      of blue collar workers in northern saudi arabia.
AB  - OBJECTIVE: To find out the level of knowledge and vaccination status of some
      expatriate ethnic groups of blue color workers. BACKGROUND: Hepatitis B (HBV)
      infection is relatively common throughout the world, but more prevalent in low
      socioeconomic and underprivileged classes. The chronic infection may lead to
      severe consequences including Hepatocellular carcinoma (HCC). METHOD: A cross
      sectional, community-based survey of some ethnic expatriate groups of blue color
      workers (n=665) living in four main areas along the Northern Borders of Saudi
      Arabia was completed in 2005. We examined knowledge of HBV and vaccination status
      and compared them with some socio-demographic factors. RESULTS: The mean age of
      the participants was 45.61 years (+/-8.44), 53% of whom were Non-Arabs (Non
      Arabic speaking). Of the total, 41.6% gave seven or more correct answers out of
      12 questions addressing knowledge about the transmission and sequelae of HBV.
      Almost 40% of the respondents had not been vaccinated while the remaining
      respondents had had three full doses of vaccination. A high level of knowledge
      (>= 7 correct answers) was significantly associated (p<0.05) with higher level of
      education, vaccination status, ethnic groups, occupation, age, marital status,
      and the time spent in Saudi Arabia. Income and type of accommodation were not
      associated (p>0.05) with level of knowledge. However, vaccination status was
      associated (p<0.05) with almost all socio-demographic factors. CONCLUSION:
      Hepatitis screening programs for expatriates in the Kingdom of Saudi Arabia
      started 10 years ago and are expected to have a great impact on the combat
      against HBV infections and their complications. However, beyond screening, health
      promotion, vaccination campaigns, and access to vaccine for the underprivileged
      classes are some necessary measures towards achieving success.

PMID- 23012173
TI  - Congenital mesoblastic nephroma: a case report.
AB  - Congenital mesoblastic nephroma (CMN) is a rare renal tumor. It can be detected
      antenatally especially with judicious use of ultrasonography.A premature female
      neonate 28 weeks' gestation, complicated by polyhydramnios, was born to a 28-year
      old woman. An abdominal mass was detected antenatally. At the end of the first
      week of life, the newborn had hypertension that was controlled by hydralazine.
      Ultrasonography and CT scan showed a right-sided renal heterogeneous solid mass.
      Right nephrectomy was performed and the histology showed CMN.

PMID- 23012172
TI  - Does academic performance in the premedical year predict the performance of the
      medical student in subsequent years?
AB  - BACKGROUND: Student admission into the College of Medicine at King Saud
      University (KSU) is dependent on the achievement of a grade point average (GPA)
      of >=3.5 /5 by the end of the premedical year. This study was undertaken to
      ascertain whether pre-selected medical students who achieve a relatively low GPA
      (<=3.75/5) in the premedical year are at risk of having academic difficulties in
      subsequent years. METHOD: A cross-sectional study of all students admitted to the
      College of Medicine at KSU during 5 academic years (1994 to 1998) was conducted
      in 2004. The likelihood of completing the program by 2004 and the dropout
      frequency were compared in the two groups based on their GPA in the premedical
      year: High GPA (>3.75) and Low GPA (<=3.75). RESULTS: During the study period,
      739 students were admitted to the college. Of these, 619 (84%) were in High GPA
      group, and 120 (16%) in the Low GPA group. Of the students with High GPA, 545
      (88%) out of 619 graduated compared with 79 (66%) of 120 in the Low GPA group (OR
      3.822 [95% CI: 2.44, 5.99]: P<0.0001). Overall, 28 students (3.8%) dropped out,
      but there was a significantly greater frequency of dropping out in the Low GPA
      group (10/120; 8.3%) compared with the High GPA group (18/619; 2.9%: OR 3.035
      [95% CI: 1.37, 6.75], P=0.01). CONCLUSION: Our results support the prerequisite
      of a minimum GPA in the premedical year before proceeding to the higher levels.
      The GPA of premedical year is a useful predictor of students who need close
      monitoring and academic support. The use of GPA in the premedical year for
      admission into medical colleges should help optimize the use of resources and
      reduce student wastage.

PMID- 23012174
TI  - Hypertension in the eastern province of saudi arabia: results of a screening
      campaign.
AB  - OBJECTIVE: To estimate the prevalence of hypertension through a screening
      campaign in the Eastern Province of Saudi Arabia, and examine its association
      with lifestyle factors. RESEARCH DESIGN AND METHODS: In 2004, all Saudi residents
      in the Eastern Province, aged 30 years and above were invited to participate in a
      screening campaign for the early detection of diabetes and hypertension. Blood
      pressure was recorded by trained nurses using a mercury sphygmomanometer, based
      on the recommendations of (JNC- VII). A positive screening test for hypertension
      was defined as systolic and/or diastolic blood pressure of >= 140 and 90 mm Hg,
      respectively. Subjects who had positive screening tests were asked to come on the
      following day for a confirmation of the reading. Hypertension was considered if
      there was a persistent reading of systolic and/or diastolic blood pressure of >=
      140 and 90 mmHg after confirmation, or when there was history of a previous
      diagnosis. RESULTS: 21% of the sample was positive from previous history or
      screening. After confirmation, the prevalence of hypertension dropped to 15.6%,
      pre-hypertension was 3.7%, whereas the prevalence of undiagnosed hypertension was
      2.8%. The prevalence rose with age. It was higher in women than in men of all age
      groups and in all sectors of the eastern province, although the mean systolic and
      diastolic BP was higher in men than women. It was higher with lower education, in
      widows and divorcees than others (P<0.0001). CONCLUSION: The yield of the
      screening for abnormal blood pressure was high. Systematic follow-up of subjects
      with abnormal screening results is vital.

PMID- 23012175
TI  - Foot care among male diabetics in family practice center, abha, saudi arabia.
AB  - OBJECTIVE: This study aims to assess the behaviors of diabetic males towards
      their foot care at Al-Manhal Center of Family Practice, Aseer Region, KSA.
      METHODOLOGY: A cross-sectional study was conducted for male diabetics in the
      Aseer region, KSA, during the first quarter of the year 2004. A questionnaire and
      physical examination of the foot were used to assess their behaviors towards foot
      care. RESULTS: All the male diabetic patients (107) who attended during the study
      period were assessed. Mean age was 58 years, mean duration of DM was 10 years.
      Good diabetic control was 24%, 37% did not know the negative effect of DM on the
      feet,9-22% had different symptoms of diabetic foot, 53% checked their feet
      regularly, 31% had fungal infection while an absence of pulse was detected in 7%.
      CONCLUSION: This study revealed that many diabetics had negative behaviors
      towards foot care. There is a need for intensive health education and regular
      assessment in order to detect, prevent and manage diabetic foot as early as
      possible.

PMID- 23012176
TI  - Stages of change in physical activity, self efficacy and decisional balance among
      saudi university students.
AB  - BACKGROUND: Determining the stages of change in physical activity (PA) helps to
      determine effective promotion of PA interventions. The aim of the study was to
      assess the readiness of students of King Saud University (KSU) to be more
      physically active and relate this to their self efficacy, perceived benefits and
      perceived barriers to PA. METHOD: A cross-sectional descriptive study was
      conducted at KSU, Riyadh, between March and May 2007, using a self-administered
      questionnaire. The total sample size was 302 randomly chosen male and female
      students. RESULTS: More than half of the students (55.3%) reported that they
      participated in PA in the action (for <6 months) and maintenance (for >= 6
      months) stages. The remaining students did not engage in PA as they were in
      precontemplation, contemplation, preparation and relapse stages. More males were
      found in the maintenance stage, but more females were found in the inactive
      stages (precontemplation, contemplation and preparation). Only 24.4% of the
      students were engaged in PA as much as three times or more/week and 9.9% engaged
      in PA regularly through out the year. About 39% of which, significantly, more
      were males did vigorous PA for 20 minutes or more. However, 4.6% described
      themselves as hyperactive. More females used the stairs, did house work and
      considered themselves moderately active. Nearly 50% had a low total score of
      perceived barriers while 85% had high perceived benefits and 63.6% had moderate
      self efficacy of PA. The main barriers perceived were time and resources. The
      score relating to barriers decreased significantly across stages of change, but
      the pattern was reversed with regard to the perceived benefits and self-efficacy
      (p<0.05). CONCLUSION: Physical inactivity is common among KSU students. A
      considerable proportion of them was not ready to become more physically active.
      The study highlights the need to adapt PA promotion programs to states of
      readiness for PA. University and public policies as well as environmental changes
      are necessary to encourage active living within the context of Islamic rules and
      Saudi culture.

PMID- 23012177
TI  - Breast cancer management delay - time for improvement: a reflection from the
      eastern province of saudi arabia.
AB  - OBJECTIVE: Breast cancer is the commonest international malignancy among women.
      Its increased prevalence over recent years in our part of the world has prompted
      women to randomly seek medical advice. Many patients are delayed for weeks to
      months prior to receiving medical treatment. This review explores the causes of
      delay and proposes possible solutions. MATERIALS AND METHODS: This review was
      undertaken at King Fahd Hospital of the University, a tertiary care center with
      the capacity of 420 beds. It accommodates a large number of referrals from the
      Eastern Province, other regions of the Kingdom, in addition to many walk-in
      patients. Most of the patients referred with breast cancer are directed to the
      breast clinic for treatment. There was random re-tracing of patients' steps from
      the discovery of the suspicious breast mass to the delivery of care. RESULTS: The
      total number of diagnosed breast cancer cases at this center between 1997-2007
      was 303, with a total number of 975 registered visits. Random retracing of these
      patients' records identified three points of delay: community related, primary
      heath care and tertiary care. It was found that the patients spent 6-15 weeks and
      around 32-38 hand offs before receiving the final care. CONCLUSION: This
      unnecessary delay creates anxiety and mistrust of the operating health system
      leading patients to seek alternative medicine or treatment abroad. A
      multidisciplinary one-stop breast oncology clinic may be the solution to the
      above problem. It may allow the fast tracking of breast cancer patients through a
      highly specialized and welltrained multidisciplinary team that offers the highest
      quality of care, thereby optimizing the chances of cure with the least delay and
      possible morbidity.

PMID- 23012178
TI  - Primary synovial sarcoma of the abdominal wall: a case report and review of the
      literature.
AB  - Synovial sarcoma is a malignant mesenchymal neoplasm which commonly occurs in the
      extremities of adults, in close association with joint capsules, tendon sheaths,
      bursae and fascial structures. Only a few cases of synovial sarcoma occurring in
      the abdominal wall have been reported. A case of a primary synovial sarcoma
      arising from the anterior abdominal wall fascial aponeurosis is presented.

PMID- 23012179
TI  - Ovarian dysgerminoma in two sisters.
AB  - Although rare, dysgerminomas are important irrespective of incidence because they
      affect women of reproductive age (i.e., <45 years). Dysgerminomas make up two
      thirds of all malignant ovarian neoplasms in women younger than 20 years. All
      dysgerminomas are considered malignant, but only one third of dysgerminomas
      behave aggressively. Their exact etiology has not been determined. Few reports
      are found in the review of the literature on the incidence of dysgerminoma and
      other germ cell tumors in families. Some of these reports focus on the genetic
      abnormalities associated with germ cell tumor and the responsible gene. Two cases
      of dysgerminomas diagnosed in two sisters aged 14 and 19 years old are presented
      here with their radiological studies.

PMID- 23012180
TI  - Evaluation of three instructional methods of teaching for undergraduate medical
      students, at king saud university, saudi arabia.
AB  - BACKGROUND: There is an international move from traditional curriculum towards
      the learner - centered, and patient-oriented curriculum. In spite of its
      advantages, problem-based learning requires a larger number of teaching staff and
      space. This study was done to compare the problem-based learning (PBL), lectures
      and modified PBL methods. METHODS: Thirty-three fifth year medical students who
      were taking the Family Medicine rotation participated in the study at the College
      of Medicine, King Saud University. Three instructors participated in the teaching
      of three topics to the three groups of students. Students acted as control for
      themselves across the three instructional methods, namely; lectures, PBL and
      modified PBL. The main outcomes were students' recall of knowledge, problem
      solving skills and topic comprehension. RESULTS: In the initial assessment, there
      was a significant difference in favor of PBL and the modified PBL regarding
      comprehension of the topic as tested by the short answer questions (p = 0.0001),
      problem solving skills as tested by the modified essay question (p = 0.002). Non
      significant results were observed at the second stage of assessment. The modified
      PBL method was the preferred one for 39% of the students, followed by the PBL
      (36%) and lastly the lectures (25%). CONCLUSION: This empirical study suggests
      some advantages for the PBL method and the modified PBL over the lecture method.
      Larger studies are needed to confirm our results of this important issue as the
      modified PBL is an affordable option for schools that can not meet the staff and
      space requirements of the PBL curriculum.

PMID- 23012181
TI  - Highly enantioselective synthesis of 1,2,3-substituted cyclopropanes by using
      alpha-Iodo- and alpha-chloromethylzinc carbenoids.
AB  - Herein, we report the enantio- and diastereoselective formation of trans-iodo-
      and trans-chlorocyclopropanes from alpha-iodo- and alpha-chlorozinc carbenoids by
      using a dioxaborolane-derived chiral ligand. The synthetically useful
      iodocyclopropane building blocks were derivatized by an electrophilic trapping of
      the corresponding cyclopropyl lithium species or a Negishi coupling to give
      access to a variety of enantioenriched 1,2,3-substituted cyclopropanes. The
      synthetic utility of this method was demonstrated by the formal synthesis of an
      HIV-1 protease inhibitor. In addition, the related stereoselective
      bromocyclopropanation was also investigated. New insights about the relative
      electrophilicity of haloiodomethylzinc carbenoids are also presented.

PMID- 23012182
TI  - Barriers against application of evidence-based medicine in general hospitals in
      aseer region, kingdom of saudi arabia.
AB  - OBJECTIVE: To explore the attitudes of doctors in the general hospitals and their
      application of evidence-based medicine (EBM) and to identify the barriers that
      hinder its use. SUBJECTS AND METHODS: This study included 346 doctors in the
      general hospitals of Aseer. A questionnaire was designed to assess their
      awareness as well as the barriers that hinder their practice of EBM. A visual
      analogue scale was used to assess their attitude. RESULTS: The attitudes of
      doctors toward aspects of EBM were generally positive. However, their use of EBM
      sources and application were generally poor. The main reasons for retrieving
      evidence were to keep them up-to-date (72.8%) and to help make clinical decisions
      (70.2%). The least mentioned reason for evidence retrieval was research (41.9%).
      Review of textbooks was the main method of evidence retrieval (71.1%), while a
      database search was the method least used (22.8%). The main barriers to the
      practice of EBM practice were "lack of facilities" followed by "lack of time",
      while the barrier least mentioned was the "lack of interest". CONCLUSIONS:
      Although doctors have positive attitudes toward EBM, their knowledge and
      application of EBM need much improvement. The main barriers to their application
      of EBM are the lack of facilities and the lack of time. RECOMMENDATIONS: The
      necessary infrastructure for the application of EBM should be made available for
      all medical staff. There is a need for special courses and hands-on workshops in
      general hospitals to address the necessary knowledge and skills of EBM are
      essential.

PMID- 23012183
TI  - Factors affecting road traffic accidents in benghazi, libya.
AB  - OBJECTIVES: The aim of the study was to evaluate the factors responsible for road
      traffic accidents in Benghazi. MATERIAL AND METHODS: Retrospective and
      descriptive studies were done in the years 2006-2007. The data was collected from
      Traffic and License Department, Benghazi. The data were analyzed, based on
      fatalities, the severely handicapped, hit and run victims and were correlated
      with age, sex, time, environmental factors, type of roads, etc. RESULTS: One
      Thousand-Two-Hundred-Sixty-Five accidents occurred between the years 2006-2007
      within the Benghazi city limits; 11.14% of the injuries were fatal; 67.35% of the
      victims had severe injuries and 21.51% escaped with minor injuries. Table 1 shows
      that 73.04% lost their lives within the city limits, 13.47% on the fly-over, and
      2.12% on minor roads connected to main roads within the city limits. The mean of
      the accidents and its standard deviation were 16.66+/- 25.67 with a variance of
      fatality of 1.54. CONCLUSION: It is concluded from the studies that major road
      traffic accidents occur because of environmental stress factors. In addition,
      fatalities and the seriousness of the accidents depend on a number of factors
      such as the age of the vehicle, safety measures, human error and time and place
      of accident.

PMID- 23012184
TI  - Guideline implementation in clinical practice: use of statistical process control
      charts as visual feedback devices.
AB  - OBJECTIVE: To use statistical control charts in a series of audits to improve the
      acceptance and consistant use of guidelines, and reduce the variations in
      prescription processing in primary health care. METHODS: A series of audits were
      done at the main satellite of King Saud Housing Family and Community Medicine
      Center, National Guard Health Affairs, Riyadh, where three general practitioners
      and six pharmacists provide outpatient care to about 3000 residents. Audits were
      carried out every fortnight to calculate the proportion of prescriptions that did
      not conform to the given guidelines of prescribing and dispensing. Simple random
      samples of thirty were chosen from a sampling frame of all prescriptions given in
      the two previous weeks. Thirty six audits were carried out from September 2004 to
      February 2006. P-charts were constructed around a parametric specification of non
      conformities not exceeding 25%. RESULTS: Of the 1081 prescriptions, the most
      frequent non-conformity was failure to write generic names (35.5%), followed by
      the failure to record patient's weight (16.4%), pharmacist's name (14.3%),
      duration of therapy (9.1%), and the use of inappropriate abbreviations (6.0%).
      Initially, 100% of prescriptions did not conform to the guidelines, but within a
      period of three months, this came down to 40%. CONCLUSIONS: A process of audits
      in the context of statistical process control is necessary for any improvement in
      the implementation of guidelines in primary care. Statistical process control
      charts are an effective means of visual feedback to the care providers.

PMID- 23012185
TI  - Control of hypertension in eastern saudi arabia: results of screening campaign.
AB  - OBJECTIVE: To assess the pattern of follow-up and level of hypertension control
      according to sociodemographic, and clinical risk factors in the participants of a
      screening campaign. RESEARCH DESIGN AND METHODS: In 2004, all Saudi residents in
      the Eastern Province, aged 30 years and above, were invited to participate in a
      screening campaign for the early detection of diabetes and hypertension. A
      structured questionnaire was completed during a face-to-face interview. The
      presence of hypertension and the place of follow-up were recorded. Blood pressure
      was measured by trained nurses using a mercury sphygmomanometer, according to the
      recommendations of The Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC
      VII). RESULTS: Thirteen point one percent of the participants had been previously
      diagnosed as having hypertension. In 34.3% of them, blood pressure was
      controlled, while 40.8% had combined uncontrolled SBP and DBP, 14.4% had isolated
      uncontrolled SBP, and 10.5% had isolated uncontrolled DBP. The blood pressure
      control was inversely associated with age. It was higher in women, singles, the
      educated, in those with BMI of less than 25 kg/m(2), and in those with positive
      history of CVD (p<0.001). CONCLUSION: Co-morbidities relevant for hypertension
      are very prevalent, so aggressive BP control is mandatory.

PMID- 23012186
TI  - Patients' knowledge and attitudes towards health education: implications for
      primary health care services in saudi arabia.
AB  - OBJECTIVES: To assess health educational activities in primary health care
      centers in Riyadh City. METHODS: The data were collected through a self
      administered questionnaire directed at adult patients who attended primary health
      care centers from February - April 2006, in Riyadh City. Out of the 750 patients
      who were selected randomly, 569 (75.9%) successfully completed the questionnaire.
      The data collected were on a set of variables including socio-demographic
      characteristics, health-related variables, source of health knowledge and
      patients' attitudes towards a number of health-related aspects. Data were
      presented and analyzed in a descriptive fashion. RESULTS: Only 20% of PHC
      patients had received health education in the past twelve months. The majority of
      respondents identified TV and friends/relatives as the main sources of their
      health education. A considerable percentage of the patients with chronic
      conditions lacked knowledge about their illnesses. The results indicate that the
      deficiency in knowledge was the result of some of the socio-demographic
      characteristics of respondents. CONCLUSION: There is an urgent need to review and
      evaluate health education programs conducted in PHC centers. Special emphasis
      should be placed on health education activities for those living with chronic
      health conditions.

PMID- 23012187
TI  - Sonographic diagnosis of gastric-outlet foreign body: case report and review of
      literature.
AB  - The diagnosis of unsuspected foreign body ingestion is a common problem in
      children. We describe a toddler who presented with persistent vomiting and
      dehydration. A plain radiograph of the abdomen did not reveal a foreign body.
      However, abdominal ultrasonography promptly identified a funnel-shaped foreign
      body obstructing the gastric outlet. This was extracted by upper endoscopy. A
      recent review of the literature shows increasing evidence that abdominal
      ultrasonography is an equally complementary diagnostic modality for ingested
      foreign bodies in children.

PMID- 23012188
TI  - Allgrove'S syndrome: case report and literature review.
AB  - This report concerns two brothers aged 10 and 18 years with long-standing
      dysphagia that started at age three and six years respectively. They had been
      diagnosed as achalasia and treated accordingly. The appearance of additional
      symptoms and clinical signs required further investigations including abdominal
      sonography, esophago-gastroduodenoscopy, barium swallow, esophageal manometry,
      computerized tomography (CT) of abdomen and brain, biochemical profiles, and
      neurologic and ophthalmic evaluations. The results of these extensive
      investigations along with the clinical evaluations were consistent with
      Allgrove's syndrome.Glucocorticoid therapy was initiated. The management
      consisted of pneumatic cardiac dilatation and initiation of cortisone treatment.
      The patients' response was impressive and they resumed most of their usual
      activities.

PMID- 23012189
TI  - Update in the treatment of cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is still a major health problem in many
      countries including Saudi Arabia. Patients with CL are seen, not only by
      dermatologists, but also by pediatricians and community physicians. Knowledge of
      available treatment options is essential. DESIGN: A literature review utilizing
      PubMed and Cochrane evidence-based library was undertaken in the last five years.
      RESULTS: Several medications and therapeutic modalities are currently in use,
      though the gold standard remains systemic antimonials. Drug resistance and
      serious side effects preclude the use of available medications. Newer therapies
      like liposomal amphotericin B, miltefosine and pentamidine are being used; while
      it is hoped that other drugs like imiquimod, tamoxifen, PDT and pentamidine
      structural analogs being tested would offer better efficacy, easier
      administration and lower toxicity. CONCLUSION: After decades of little advance in
      the treatment of leishmaniasis, there are now several options with newer
      compounds and combinations of these.

PMID- 23012190
TI  - Perceptions of primary health care (phc) doctors on the prevention of coronary
      heart disease (chd) in riyadh, saudi arabia.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of death throughout
      the world. PHC doctors are in a unique position to prevent CHD and promote health
      in the population. However, the perception of PHC doctors on CHD prevention has
      not been well documented. OBJECTIVES: To explore and examine the perception of
      PHC doctors on the prevention of CHD. SUBJECT AND METHOD: A questionnaire survey
      of all PHC doctors attending a continuing medical education (CME) activity in
      Riyadh city. The questionnaire was designed and piloted with local PHC doctors
      before being used in this survey. RESULTS: All the 77 PHC doctors responded
      (100%) and almost all the them (97.4%) agreed that the primary prevention of CHD
      was an essential task. Fifty-two participants (67.53%) confirmed that little
      attention had been paid to the primary prevention of CHD. While the majority of
      respondents (71.43%) felt that the primary prevention of CHD was an easy task, a
      significant minority (23.37%) disagreed. Interestingly, 70 (90.91%) respondents
      were not aware of any local literature on how to achieve primary prevention of
      CHD and would like to have the literature made available to them. Finally,
      participants indicated that the percentage prevalence of CHD risk factors among
      their patients was high. CONCLUSION: the findings of this survey confirm a
      general feeling that the primary prevention of CHD is not being given enough
      attention. Participants accepted that the primary prevention of CHD was an
      essential part of their work, but the lack of local literature and research on
      this vital area was a major concern.

PMID- 23012191
TI  - Assessment of ambient noise levels in the intensive care unit of a university
      hospital.
AB  - BACKGROUND: Noise is recognized as a source of hazard to the patient's
      environment. Studies have also shown that it has a direct impact on mortality and
      morbidity as a result of sleep deprivation which affects the immunity of
      critically ill patients. OBJECTIVES: The aim of this study was to measure levels
      of environmental noise in a six- bed, open-plan general medical intensive care
      unit (MICU). METHODS: Levels of exposure to environmental noise were assessed in
      the intensive care unit of King Fahad Hospital of the University (KFHU) where
      measurements of environmental noise were taken using calibrated sound level meter
      during shifts of working days and weekends. RESULTS: Statistical analysis
      revealed that there were no significant differences between noise levels in the
      morning, evening and night shifts of working days and weekends in the ICU of KFHU
      (p value =0.155, 0.53 and 0.711) respectively. There was no significant
      difference between overall level of exposure to noise in the working days and
      weekends as well (p-value=0.71). However, the assessed levels of exposures to
      noise were still higher than stipulated international standards. CONCLUSION: Some
      sources of environmental noise, such as the use of oxygen, suction equipment or
      respirators are unavoidable. Nevertheless, hospital ICUs should have measures to
      minimize the level of exposure to noise in the ICU. Further research in this area
      might focus on the noise level and other modifiable environmental stress factors
      in the ICU that affect patients as well as the staff.

PMID- 23012192
TI  - In vivo effect of some home spices extracts on the toxoplasma gondii tachyzoites.
AB  - Toxoplasmosis drugs have the longest history and are still the first choice for
      most conditions. Alternative drugs such as Co-trimoxazole and Tetracycline have
      been tried and acclaimed successful. The lack of general acceptance, however, is
      an indication that the results are not very convincing. A wide range of
      antibiotics is urgently needed for patients with drug reaction or resistance
      problems. The anti-toxoplasmic activity of water and ethanol extracts as well as
      the oil of some home spices (Piper nigrum, Capsicum frutescens, Cinnamomum cassia
      and Curcuma longa), were evaluated in murine models of intraperitoneal infection
      using the RH strain of Toxoplasma gondii. Female mice were infected with 2*10(2)
      tachyzoites/ml, and then treated intraperitoneally with the home spices at 100
      and 200 mg/kg/day for seven days. The tested extracts reduced the mean number of
      tachyzoites present in the peritoneal fluid of the experimental mice. The most
      effective extract was Curcuma longa ethanol extract which showed a 98.6% and
      99.2% inhibition of the growth of Toxoplasma tachyzoites in 100 and 200 doses
      respectively compared to the control infected untreated mice.

PMID- 23012193
TI  - Challenges to saudi medical education in the third millennium.
AB  - Medical education began in Saudi Arabia in 1969 when King Saud University, the
      first medical school was established. Since then globalization has brought
      numerous challenges. In this paper, we review the status of medical education and
      its expected future projects.

PMID- 23012194
TI  - Acute Plasmodium vivax malaria presenting with pancytopenia secondary to
      hemophagocytic syndrome: case report and literature review.
AB  - Pancytopenia as an initial manifestation of acute plasmodium vivax malaria is
      extremely rare and mainly reported with plasmodium falciparum. We report a 37-
      year old Nepali patient who recently came to Saudi Arabia and presented with a
      three-week history of intermittent fever, chills and rigor. She was found to have
      spleenomegaly, pancytopenia, hyperferrtinemia, and hypofibronogenemia with
      positive peripheral blood smear for plasmodium vivax. The patient had a full
      recovery from pancytopenia with oral chloroquine.

PMID- 23012195
TI  - A right coronary artery aneurysm associated with chest pain: a case report.
AB  - A 46-year-old female is the first to be described from Saudi Arabia with a right
      coronary artery aneurysm associated with chest pain. A review of the coronary
      aneurysm is discussed with its implications on our patient.

PMID- 23012196
TI  - Approach to the child with recurrent infections.
AB  - Children with a history of recurrent, severe, or unusual infections present a
      diagnostic challenge. It is important to maintain a high index of suspicion for
      the diagnosis of immunodeficiency, for early diagnosis and treatment can improve
      outcome. Differentiation between infections caused by common risk factors, or
      immune dysfunction should be based on a detailed history and physical examination
      and, if indicated, followed by appropriate laboratory studies. This paper aims at
      providing guidelines for the evaluation of children with recurrent infections. It
      provides an overview of the diagnostic approach including important details
      required from the history, physical examination, and an appropriate choice of
      screening test to be ordered.

PMID- 23012197
TI  - Evaluation of the availability of cold chain tools and an assessment of health
      workers practice in dammam.
AB  - AIM: To evaluate the availability of cold chain tools and assess the practice of
      health workers in immunization rooms in health clinics in the Dammam area.
      METHODOLOGY: A cross-sectional approach was used for the study. A stratified
      random sampling technique was used to obtain a sample of 10 governmental primary
      health care centers from the total of 20 centers that serve the Dammam area, and
      five out of 17 private health clinics. The Maternity and Child Health Hospital
      was included. A field survey was done at all sample sites. Data collection,
      analysis, and interpretation were done from July to September 2007, using a check
      list designed for this study according to cold chain criteria set by the Ministry
      of Health (MOH) and World Health Organization (WHO). RESULT: According to the MOH
      and WHO criteria, around 91% of governmental health facilities (GHF) and 80% of
      private health care (Private HC) rooms were suitable. Less than 20% of the
      private HC maintained proper vaccine temperatures during storage, compared with
      all (100%) of GHF clinics (p<= 0.05). The difference in the appropriate handling
      and usage of vaccines during immunization sessions was also highly significant
      between GHF (90-100%) and private HC (20%) (p<= 0.05). The knowledge of
      refrigeration maintenance by GHF and private HC health workers including keeping
      the refrigerator from dust, emergency retrieval and storage procedures in case of
      equipment failure or power outages, keeping the range of recommended temperature
      between 2 degrees C- 8 degrees C was 100% for GHF and for the Private HC's ranged
      from 20%-40% (p<=0.05). Vaccine vials on the refrigerator shelves was appropriate
      in all (100%) of the GHF and in only 40% for the Private HC (P<=0.05).
      CONCLUSION: This study showed that private health clinics did not comply with
      standards defined by the MOH or WHO for cold chain tools and needed constant
      supervision and training as health care professionals. All personnel handling
      vaccines should understand the purpose and function of various cold chain tools
      in their setting for immunizations.

PMID- 23012198
TI  - Pattern of khat abuse and academic performance among secondary school and college
      students in jazan region, kingdom of saudi arabia (ksa).
AB  - BACKGROUND: Khat is a widely-abused psychoactive substance in East African
      countries, Yemen and Southwestern areas of the Kingdom of Saudia Arabia (KSA),
      especially in Jazan region. However, patterns of Khat consumption as well as its
      adverse consequences on academic work are not well studied. OBJECTIVE: The study
      was conducted to assess the pattern of Khat abuse and its associated academic
      effect on Secondary School and College students in Jazan region, KSA. METHODS: A
      cross-sectional study was conducted in May 2006, in Secondary Schools and
      Colleges in Jazan region, KSA. Students in each class were selected by systematic
      random sampling technique. Self-administered questionnaire was used for data
      collection. Data was processed and analyzed using the Statistical Package for
      Social Sciences (SPSS). RESULTS: Most Khat sessions were conducted in homes
      (43.8%) and friend's houses (37.0%). The mean duration of a Khat session is 6.1
      +/-3.13 hours and 5.5% chew Khat for 12-18 hours. Most Khat sessions take place
      at the weekends (48.4%) usually after 8 p.m (69.8%). CONCLUSION: Most chewing
      sessions took place at weekends usually in social gatherings after 8 p.m. with an
      average duration of about 6 hours. Smoking and educational problems were more
      prevalent among Khat chewers. Strong preventive and control measures including
      early interventions and increase of awareness need to be implemented.
      Recreational alternatives for young people and families especially at weekends
      and holidays have to be found.

PMID- 23012199
TI  - Job satisfaction among the academic staff of a saudi university: an evaluative
      study.
AB  - BACKGROUND: Job satisfaction is a major determinant of job performance, manpower
      retention and employee well-being. OBJECTIVES: To explore the state of job
      satisfaction among the academic staff of King Faisal University - Dammam (KFU-D),
      and detect the areas and groups at a higher risk of being dissatisfied. METHOD: A
      fully-structured 5-option Likert-type Job Satisfaction Questionnaire (JSQ)
      composed of an evaluative item and eleven domains making a total of 46 items was
      used. It was distributed by internal mail to all the 340 academic staff, 248 of
      whom returned completed questionnaires (response rate = 72.9 %). FINDINGS: The
      overall mean Job Satisfaction Rate (JSR) was 73.6 %. The highest JSR's were found
      in three domains ("Supervision", "Responsibility", and "Interpersonal
      Relationships"), and the lowest in four others ("Salary", "My Work Itself",
      "Working Conditions", and "Advancement"). The JSR was significantly lower among
      Saudi nationals, females, those below age 40, those from clinical medical and
      Dentistry departments. Multiple Regression identified six independent variables
      which conjointly explained 25 % of the variance in job satisfaction (p < 0.0001).
      These were: being an expatriate, above the age of 50, serving the university for
      less than one or more than ten years, and, not from a clinical department of
      Medicine or Dentistry. CONCLUSIONS: Most staff were satisfied with many aspects
      of their jobs, but there was significant dissatisfaction with several job-related
      aspects and demographic features. Appropriate interventions are indicated.
      Further studies are needed to confirm the present findings and to monitor future
      trends.

PMID- 23012200
TI  - Impairment of quality of life among adults with skin disease in king fahad
      medical city, saudi arabia.
AB  - OBJECTIVES: The objective of the study was to assess the quality of life in
      patients with skin disease. SUBJECTS AND METHODS: A 6-month cross-sectional study
      was conducted in the Dermatology Clinic at King Fahad Medical City, Riyadh,
      Kingdom of Saudi Arabia. The study sample consisted of all 297 adult patients
      with dermatological conditions attending clinic but without associated
      psychiatric disease. They completed a self-administered Arabic version of the
      Dermatology Life Quality Index questionnaire (DLQI), containing ten items. The
      data was analyzed according to disease, age and gender. RESULTS: The gender
      distribution of the study sample was 73% female and 27% male. The mean age was
      29.4 years. The proportions of patients with various diagnoses were: sebaceous
      and apocrine gland disorders 31.3%, eczematous dermatitis 18.5%, cutaneous
      infections 13.5%, and pigmentary disorders 10.8%. The mean DLQI of all patients
      was 8.32. Patients with papulosquamous disorders recorded the highest mean DLQI
      score of 15.28, followed by immunological disorders with 11.11, eczematous
      dermatitis with 9.55, and miscellaneous disorders with 10.91. The mean DLQI was
      higher among females (9.02) than males (6.46). Age had no influence on the degree
      of impairment. CONCLUSION: Measuring the impairment of the quality of life in
      dermatology patients is an important aspect of management. It allows clinicians
      to assess the extent and nature of the disability so that an appropriate
      management regimen can be implemented and its effectiveness assessed.

PMID- 23012201
TI  - SEROPREVALENCE OF ERYTHROVIRUS B19 IgG AMONG SAUDI BLOOD DONORS IN MAKKAH, SAUDI
      ARABIA.
AB  - OBJECTIVES: To determine the seroprevalence of immunoglobulin G (IgG) to
      erythrovirus B19 in Saudi blood donors in Makkah. Saudi Arabia. SUBJECTS AND
      METHODS: A total of 578 blood (serum) samples were tested for erythrovirus B19
      specific-IgG antibody among Saudi blood donors in Makkah. Saudi Arabia. RESULTS:
      Erythrovirus B19-specific-IgG antibodies were detected in 441/578 (76.3%) of
      Saudi blood donors of different age groups. CONCLUSION: This study indicated that
      76.3% of Saudi blood donors in Makkah city, Saudi Arabia, had been exposed to
      erythrovirus B19. This result is in accordance with previous studies performed in
      other countries.

PMID- 23012202
TI  - Experience of a workshop on communication skills in health professional
      education.
AB  - BACKGROUND: The teaching of communication skills is gaining increasing attention.
      However, the opportunities for faculty development are limited. This study
      highlights an attempt by the Medical Education Unit, King Fahd Hospital of the
      University, Al-Khobar, to raise the awareness of faculty to this vital area by
      organizing a one-day workshop. METHOD: A one-day workshop was organized to
      improve the awareness of the participants to the role of communication skills
      such as doctor-patient interaction, breaking bad news, counseling and conflict
      management. In all, 168 participants consisting of faculty members, interns and
      students, both male and female participated. The sessions included interactive
      lectures, video demonstrations and role play. RESULTS: The feedback from the
      participants indicated that the objectives of the workshop were largely realized.
      The presentations by speakers were of high quality. However, the participants
      wanted more small group activities and video-demonstrations that were relevant to
      the local environment. CONCLUSION: By and large, the one-day workshop was found
      to be a practical model for an initial attempt to raise awareness. Further work
      is needed to organize more intensive workshops on specific issues related to
      communication skills.

PMID- 23012203
TI  - The self-limiting nature of statin-induced rhabdomyolysis.
AB  - Statins have come to the forefront of treatments for hyperlipidemias, coronary
      artery diseases and strokes. They have been shown to cause myotoxicity and
      rhabdomyolysis. In most cases, rhabdomyolysis is self-limiting and needs
      supportive therapy. Two cases of statin-induced rhabdomyolysis are reported
      emphasizing the definition, risk factors, clinical features and the self-limiting
      nature of the disorder.

PMID- 23012204
TI  - Information superhighway........Are we in the fast lane?

PMID- 23012205
TI  - International controversies in interpreting the mantoux test with special
      reference to saudi arabia.
AB  - There is a general decline in the incidence of pulmonary tuberculosis (PTB) in
      developed countries, but infection by HIV has increased the incidence of PTB in
      affected countries. There are no signs of a similar decline in the incidence of
      PTB in some developing countries. The Mantoux technique for tuberculin testing
      continues to be among the effective diagnostic tools. The medical literature and
      textbooks of medicine show disagreement as to what constitutes a positive
      (specific) tuberculin reaction. This short review was intended to cite some
      examples of these differences and suggest a cutting point for use in the Kingdom
      of Saudi Arabia (KSA) based on the prevalence of environmental mycobacteria
      (Mycobacteria other than M. tuberculosis, MOTT). From this review different
      researchers within the KSA used different cut-off points at a time that the
      prevalence of MOTT was unknown, until 1993 when it was reported to be as low as
      3.8/1000 population (based on sputum culture) and that the Kingdom is categorised
      among the middle PTB prevalent countries. Consequently, it seems appropriate to
      have 5 mm as a cutting point (positive) in all unvaccinated patients,
      particularly for those who were in contact with an infectious case, or having
      symptoms compatible with PTB, and also patients who were immuno-compromised as in
      HIV infection. This cut-off point can be revised and raised to 8 mm provided that
      the prevalence of PTB becomes lower than the current reported rate and MOTT
      prevalence remains low, but the 5 mm cutting point should remain for the
      aforementioned categories of patients.

PMID- 23012207
TI  - Factors associated with diarrhoea prevalence in saudi arabia.
AB  - The weather of Saudi Arabia is hot and dry for most of the year. The country is
      devoid of surface water which often help the transmission of diarrhoeal diseases.
      Nevertheless, this country is not free from diarrhoeal diseases. The role of such
      factors as crowding, patterns of water use, sanitation, quality of housing,
      feeding practices and region of residence have not been adequately studied. The
      1987 National Child Health Survey data were used to earmark the roles of the
      aforementioned determinants of diarrhoea in Saudi children aged below six. A
      stratified and representative sample of 8,566 married women living in rural and
      urban areas were interviewed by 120 female nurses. There were about two episodes
      of diarrhoea per child per year. Children aged 6 to 23 months had nearly double
      the prevalence rate of the older children. Children from rural areas and the
      southern region had higher rates than children from other areas. Children who
      were both breast and bottle fed, children of 1-4 member families and of families
      with 3 or more persons per room had higher prevalence rates. Children of families
      whose homes had earthen floors, those who used well water and those without
      toilet facilities who used open fields for defecation had significantly higher
      rates. In spite of adverse climate and little use of surface water these factors
      were significantly associated with higher prevalence rates of diarrhoea in Saudi
      children under six years of age.

PMID- 23012206
TI  - Cardiovascular risk and risk reduction: a review of recent literature.
AB  - An account is given of recent literature regarding the major cardiovascular risk
      factors. It considers high blood pressure, high blood cholesterol, smoking, as
      well as insulin resistance and its metabolic consequences. The focus is on the
      current available evidence in terms of causal associations of these risk factors
      with the occurrence of cardiovascular disease, and the evidence of the benefits
      of risk factor lowering. The multiplicative effect of risk factors and their
      multifactorial role in the genesis of cardiovascular disease is now firmly
      established and will affect the mode of approach to preventive measures. The main
      preventive options currently available are twofold, a population-wide approach
      and a high risk approach. The suitability of primary health care as one of the
      main providers of preventive care is today widely acknowledged. The need for
      cardiovascular risk assessment to be multifactorial and made in terms of overall
      actual risk is of paramount importance. The implications of this overall issue
      for countries like those of the Middle East, where the prevalence of
      cardiovascular disease is on the rise, are of great concern.

PMID- 23012208
TI  - Assessment of the Knowledge of Primary Health Care Staff about Primary Health
      Care.
AB  - The orientation about Primary Health Care among staff working in the PHC centers
      was assessed. Staff members numbering 909 were studied. The main criteria for
      judging orientation were a working knowledge of the definition and elements of
      PHC in addition to knowledge of the meaning of the word Alma Ata. Differences of
      this knowledge depending on sex, age, spoken language, type of job, postgraduate
      experience, previous experience in PHC and previous training in PHC were
      assessed. The main findings of the study were that the correct definition of PHC
      was known by only 51.4%, functions of PHC by 62.6%, and what Alma Ata, means in
      terms of PHC was known by 76.2% of the staff. This knowledge was significantly
      better in females than males, non-Arabic speaking staff than those who spoke
      Arabic, General practitioners and nurses than other staff; it was better in those
      staff who had long postgraduate experience, previous experience or previous
      training in PHC.In conclusion, the study reveals the current status of awareness
      of PHC staff of the implications of simple concepts of PHC and points to the
      importance of the orientation of staff towards these concepts in order to help
      them practice PHC effectively.

PMID- 23012209
TI  - Evaluation of Drug Prescribing Habits in a Postgraduate Teaching Set-up in Saudi
      Arabia.
AB  - The objective of this retrospective study was to assess the rationale behind the
      practices of drug use in a teaching hospital that provides primary health care. A
      total of 500 prescriptions issued 6y faculty and post-graduate fellowship
      residents in the Department of Family and Community Medicine were collected. An
      evaluation of these prescriptions was carried out using the INRUD indicators of
      drug prescribing. The results of this study showed that apart from the low
      percentage (43.2%) of drugs prescribed generically, the application of INRUD
      indicators of drug prescribing appeared satisfactory when compared to similar
      studies from local and other developing countries. This study recommends a review
      of the current teaching of Pharmacology and Therapeutics to undergraduates in
      general & in particular to postgraduates specializing in Family & Community
      Medicine. Quality assurance systems on drug prescribing at primary health care
      centers should be established and implemented. Large scale studies similar to
      that under discussion should be encouraged.

PMID- 23012210
TI  - Growth patterns of jordanian children: a national study.
AB  - This study examined the growth patterns of Jordanian children below three years
      of age in comparison with the NCHS reference population. Weight and length
      measurements of 1224 boys, and 1120 girls were obtained from a national
      multipurpose study of Jordanian preschool children carried out in 1984. The study
      results showed that children of both sexes grew at Gentiles that were close and
      parallel to the NCHS in the first quarter of the first year. However, both weight
      and length Gentiles departed from the NCHS counterparts later on with length
      showing marked differences from the reference. The differences observed between
      the local and the NCHS reference population suggest that the NCHS should be used
      as a target for planning and evaluation of' intervention programs at a national
      level while the need for the local standards to assess individual cases remains a
      necessity.

PMID- 23012211
TI  - Trachoma in an omani village - a health care study.
AB  - This paper reports the findings of a study carried out on 289 families in rural
      Oman, to assess the knowledge of trachoma in a defined community, identify the
      determinants of continued transmission and endemicity of the disease, and to
      assess the effect of health education provided by medical students.The study
      identified the prevalence of illiteracy, large family size and overcrowding as
      potential risk factors. Lack of knowledge in a significant number of families
      about causes, prevention and transmission of trachoma led to practices that
      promoted the spread of the disease.We found that episodic health education by
      medical students did not have any lasting impact on the community. Between
      families who had received such health education and those who had not, there were
      few significant differences regarding misconceptions about the disease and
      undesirable practices.The findings of this study concerning deficiency in
      knowledge, misconceptions and incorrect practices about trachoma are being
      utilised to plan a subsequent health education programme for the villagers.

PMID- 23012213
TI  - "Hot Topics in Neonatology; December 12-14, 1993, Washington DC, USA".
AB  - As a guest discussant, I had the pleasure and privilege of being invited to this
      important meeting which is held yearly. As the name implies, this meeting has its
      focus on subjects in which there was tremendous changes in the field of Neonatal
      Medicine, also on subjects where there is unanswered questions and controversial
      issues. The meeting was organized and chaired by Prof. J.F. Lucey, a well-known
      celebrity from the Pediatric World and the editor of the highly reputed journal,
      Pediatrics.The topics that were chosen for this year included five subjects based
      on the criteria mentioned above.

PMID- 23012212
TI  - Developmental Milestones and Additional Disabilities in Children attending ESN/M
      School in Dammam, Saudi Arabia.
AB  - Information about the extent of additional disabilities presented and experienced
      by the mentally retarded children is essential for proper health services
      planning for this group.The objective of this case-control study was to identify
      the developmental milestones and additional disabilities of mildly mentally
      retarded male children. Sixty-nine parents of mildly mentally retarded male
      children (MMR group) and a similar number of matched parents of normal male
      children (control group) were interviewed and a questionnaire was
      completed.Generally, the MMR group children smiled, sat, walked, talked and
      became continent for urine and bowel significantly later than the control group.
      Additional disabilities in the children of the MMR group were in the form of
      speech (65%), visual (28%), limb weakness (20%), hearing (16%), convulsive
      disorder (15%) and other disabilities (10%).Well structured health education and
      I.Q. screening programs were recommended for early detection of mental
      retardation and subsequent entry to special education. Institutes for mentally
      retarded children in the Kingdom need to be better vocationally equipped. The
      role of Family and Community Physicians in early detection and management was
      also emphasized.

PMID- 23012214
TI  - Differential immunogenicity and allergenicity of native and recombinant human
      lactoferrins: role of glycosylation.
AB  - Human native milk lactoferrin (LF) and recombinant forms of lactoferrin (rLF) are
      available with identical aa sequences, but different glycosylation patterns.
      Native lactoferrin (NLF) possesses the intrinsic ability to stimulate vigorous
      IgG and IgE antibody responses in BALB/c mice, whereas recombinant forms
      (Aspergillus or rice) are 40-fold less immunogenic and 200-fold less allergenic.
      Such differences are independent of endotoxin or iron content and the glycans do
      not contribute to epitope formation. A complex glycoprofile is observed for NLF,
      including sialic acid, fucose, mannose, and Lewis (Le)(x)  structures, whereas
      both rLF species display a simpler glycoprofile rich in mannose. Although Le(x) 
      type sugars play a Th2-type adjuvant role, endogenous expression of Le(x)  on NLF
      did not completely account for the more vigorous IgE responses it provoked.
      Furthermore, coadminstration of rLF downregulated IgE and upregulated IgG2a
      antibody responses provoked by NLF, but was without effect on responses to
      unrelated peanut and chicken egg allergens. These results suggest glycans on rLF
      impact the induction phase to selectively inhibit IgE responses and that
      differential glycosylation patterns may impact on antigen uptake, processing
      and/or presentation, and the balance between Th1 and Th2 responses.

PMID- 23012215
TI  - Activation energy for the self-metalation reaction of 2H-tetraphenylporphyrin on
      Cu(111).

PMID- 23012216
TI  - Comparison of endoscopic submucosal dissection with laparoscopic-assisted
      colorectal surgery for early-stage colorectal cancer: a retrospective analysis.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is increasingly
      being used to resect early colorectal carcinoma, despite the technical
      difficulties associated with the procedure. Laparoscopic-assisted colorectal
      surgery (LAC) is an alternative to open surgery for colorectal cancers, and ESD
      was recently introduced as another alternative. In this study, we compared ESD
      with LAC as minimally invasive treatments for early colorectal cancer. PATIENTS
      AND METHODS: The study included 589 patients (297 patients with colorectal
      intramucosal or slightly submucosal invasive cancers undergoing ESD; 292 patients
      with T1 colorectal cancers undergoing LAC) who were treated at National Cancer
      Center Hospital in Tokyo, Japan, between January 1998 and September 2008. The
      clinical outcomes of ESD and LAC were evaluated retrospectively and compared on
      the basis of data that were originally collected prospectively. RESULTS: In the
      ESD group, mean tumor size was 37 mm, mean procedure time was 106 minutes, and
      the en bloc and curative resection rates were 87 % and 80 %, respectively. There
      were 14 perforations (4.7%) and 5 cases of postprocedure bleeding (1.7%); all
      complications were successfully managed endoscopically except for one of the
      perforations, which required emergency surgery. In the LAC group, mean tumor size
      was 20 mm, mean operation time was 206 minutes, and complications included 31
      wound infections, 2 pelvic abscesses, 3 anastomotic leakages, and 1 anastomotic
      bleed. Stomas were necessary in 93 % of the patients who underwent LAC for rectal
      cancers located below the peritoneal reflection. CONCLUSIONS: ESD was associated
      with a lower complication rate than LAC, with favorable en bloc and curative
      resection rates. The safety profile and possibility of curative treatment with
      colorectal ESD provide advantages for the treatment of early colorectal cancers
      with nul risk of lymph node metastasis.

PMID- 23012217
TI  - Endoscopic submucosal dissection or transanal endoscopic microsurgery for
      nonpolypoid rectal high grade dysplasia and submucosa-invading rectal cancer.
AB  - BACKGROUND AND STUDY AIMS: Transanal endoscopic microsurgery (TEM) has been shown
      to be highly effective for early rectal cancer, and endoscopic submucosal
      dissection (ESD) has been introduced to treat noninvasive colorectal neoplasia.
      The aim of this study was to compare the outcomes of ESD and TEM for superficial
      early rectal cancer. PATIENTS AND METHODS: We retrospectively analyzed 63
      patients with nonpolypoid rectal high grade dysplasia or submucosa-invading
      cancer who were treated with ESD or TEM, and compared clinical outcomes and
      safety between the treatment groups. RESULTS: 30 patients underwent ESD and 33
      underwent TEM. For ESD compared with TEM, en bloc resection rates were 96.7% vs.
      100% (P = 0.476) and R0 resection rates were 96.7 % vs. 97.0 % (P = 1.000). There
      were no cases of local recurrence or distant metastasis in either group.
      Antibiotics were required in 11 patients (36.7%) in the ESD group and 33 (100%)
      in the TEM group (P < 0.001). There was no difference in net procedure time
      although ESD was associated with shorter total procedure time and hospital stay
      than TEM, with mean (standard deviation [SD]) 84.0 (51.2) vs. 116.4 (58.5) min (P
      = 0.0023), and 3.6 (1.2) vs. 6.6 (3.5) days (P < 0.001), respectively. There were
      no significant differences in complications between the two groups. CONCLUSIONS:
      Both ESD and TEM are effective and oncologically safe for treating nonpolypoid
      rectal high grade dysplasia and submucosa-invading cancers. ESD has the
      additional advantages of minimal invasiveness and avoidance of anesthesia.
      Therefore, ESD could be recommended as a treatment option for superficial early
      rectal cancers.

PMID- 23012218
TI  - Patient Satisfaction - A valid tool of quality assurance (C. Q. I).

PMID- 23012219
TI  - Health understanding and its effect on health outcome.
AB  - Literature regarding health belief models, health understanding and their effect
      on health outcome is reviewed. Aspects of the major elements comprising health
      understanding - including lay explanations of illness, locus of control and the
      affective meaning of symptoms - are described. The particular problems posed by
      utilising these models in a developing Middle Eastern country are discussed,
      together with the importance of applied research to assess the feasibility of
      improving health outcome by enhanced health understanding.

PMID- 23012220
TI  - Patient satisfaction survey in a teaching hospital in saudi arabia: preliminary
      results.
AB  - BACKGROUND: Patient satisfaction is a useful indicator of the quality of health
      care, but there is no one universally acceptable tool for measuring it. In Saudi
      Arabia, such studies are, few. SETTING: In-patients in a teaching hospital.
      METHODOLOGY: Opinions of hospital in-patients were sampled by means of a self
      administered questionnaire over a period of 12 consecutive months. Fright areas
      were evaluated: professional services from medical, nursing anal admission staff,
      and four amenities, i.e. room and linen, meals, and provision for telephone and
      television. RESULTS: A total of 1,319 patients were surveyed, forming 7.9% of the
      17,536 admissions. Patients were satisfied with professional services from
      medical staff. However, they were dissatisfied with silence in wards during day,
      taste, temperature and variety of meals, as well as provisions for telephone and
      television. Remedial actions had been taken. CONCLUSIONS: We concluded that the
      results indicated areas of patients' dissatisfaction in our hospital, and that
      such surveys are unique to the hospital involved. We recommend the method used
      here: it is easy to use, cost-effective, and beneficial to patients.

PMID- 23012221
TI  - Permanent diversion stomas: "guidelines for muslim physicians and patients".
AB  - BACKGROUND: Ethical issues in medical practice are increasing in number,
      diversity and complexity and posing professional diemmas for physicians. It is
      the duty of Muslim physicians in collaboration with jurists, to resolve these
      issues. OBJECTIVES: These guidelines aim at answering the following two
      questions: 1. On religious grounds to what extent is a Muslim patient bound
      ground to accept surgical treatment requiring permanent diversion of stool and
      urine? 2. What should be the role of medical staff in convincing the patient aril
      his relatives to accept diversion stomas. METHODS: 1. Identification of the
      consequences of diversion stomas. 2. Verification of the religious rule in
      relation to seeking treatment. 3. Identify the effect of carrying a stoma bag on
      the patient's purity during worship 4. Outline the role of the medical staff in
      convincing the patient vial his relatives to accept a needed stoma  RESULTS
      #ENTITYSTARTX00026; DISCUSSION: A Muslim patient needing a permanent diversion
      stoma has a religiously proven duty to listen to the instructions of a proficient
      physician in order to save himself if safety is most probable. Carrying a stoma
      bag does not interfere totally with patients purity. The exact role of medical
      staff in convincing the patient and his relatives to accept the procedure is
      discussed.

PMID- 23012222
TI  - Hospitalisation due to Acute Poisoning in Children - Tabuk Experience.
AB  - BACKGROUND #ENTITYSTARTX00026; METHOD: Acute poisoning in children is still a
      major problem in our community, taking up a lot of resources from the health care
      system. We report here the result of' a three year study (1991-1994) carried out
      in the Northwest Armed Forces Hospital, Tabuk, Saudi Arabia regarding
      hospitalisation of children as a result of poisoning. RESULTS: Sixty eight
      children below twelve years of age were admitted, accounting for a total of
      approximately 175 inpatient days. The majority of them (n=60, 88.2%) were below
      the age of five years. house hold products (16.2%), kerosene (10.3%) and
      antihistamines (19.1%) were the commonest ingested substances. An analysis of
      various aspects of this problem and the review of relevant literature is
      included. CONCLUSIONS: Health education about safe storage of medicine at home
      and a knowledge of first aid is very necessary. This may prevent the occurence of
      such accidents and reduce morbidity.

PMID- 23012223
TI  - The introduction of epidemiology in training future doctors: the oman experience.
AB  - This paper highlights the emphasis put on epidemiology in the training of future
      doctors at Sultan Qaboos University. It describes the special features of the
      teaching of epidemiology making it needs-oriented with continuous practical
      application in the field throughout the preclinical period. The students take an
      active part in planning field studies using their knowledge of epidemiology.
      Integration of epidemiology with statistics enables the students to analyze and
      interpret their own data thus obtaining a quick feed-back of the epidemiological
      studies conducted by them. They apply their knowledge of epidemiology to evaluate
      the data and formulate intervention programmes.Close collaboration with the
      Ministry of Health provides an opportunity for the students to orient themselves
      with the important health problems of Oman and participate in the country's
      national programs. The scheduling of courses and continuation of application of
      epidemiology in the clinical years help to reinforce their knowledge of
      epidemiology and statistics for the clinical period and subsequent
      postgraduation.

PMID- 23012224
TI  - Asymptomatic salmonella, Shigella and intestinal parasites among primary school
      children in the eastern province.
AB  - OBJECTIVE: The main objective of this study was to determine the prevalence of
      some potential entropathogens among primary school children. METHODOLOGY: This
      study was conducted, on a sampled population of3258 primary school going children
      in the age group of 6-11 years. They were investigated for the presence of some
      potential enteropathogens in their stools. RESULTS: The overall prevalence of
      enteropathogens was 10.44 percent. Salmonella and Shigella species were found
      among 114 percent children. Multiple drug resistance was common in the isolated
      species of Salmonella and Shigella with ma exception of Nalidixic acid and
      cephalothin in Shigella. The prevalence rate of parasitic infection was 9.30%.
      The most common parasite found was giardia lambia, 8.16 percent, and next most
      common was Entamoeba histolytica 0.74%, followed by other parasites: (Hemenolepis
      nana, Ascaris lumbricoides, Trichuris trichuira and Enterobious vermicularis, in
      order of their frequencies). CONCLUSION: This study lays emphasis on the
      importance of asymptomatic carriers as a potential source of infection and
      demonstrates the emergence of resistance in salmonella and Shigella species.

PMID- 23012225
TI  - The Pupillographic SleepinessTest in adults: effect of age, gender, and time of
      day on pupillometric variables.
AB  - OBJECTIVES: The Pupillographic Sleepiness Test (PST) measures the level of
      alertness based on spontaneous oscillations in pupillary size. Reference data are
      available for male and female adults within the age range 20-60 years. The aim of
      the present multicenter study was to extend the age range for reference data from
      20 to 79 years. METHODS: A total of 239 healthy subjects, selected from three
      different centers (Berlin, Regensburg, and Vienna), were administered the PST.
      Data were analyzed with respect to possible effects of age, gender, and time of
      day on the pupillary unrest index (PUI) and the pupil diameter (PD). RESULTS:
      Reliable data were available in 85.8% of the entire study sample and in 82.4% of
      elderly subjects (60+ years). Age-related changes were identified for the PUI and
      PD. There was no effect of gender on pupillometric variables as revealed by
      univariate analysis. The PD was found to be smaller in the afternoon compared
      with the morning. However, if subjects aged 60+ years were excluded from the
      analyses, the age-related changes disappeared and a time-of-day effect regarding
      the PUI became apparent. CONCLUSIONS: PUI and PD were found to decrease with
      increasing age. In addition, the present data show that nonreliable PST data
      occur more frequently in the elderly probably because of dry eyes, inadequate
      testing conditions, and technical resolution limitations. Thus, the PST results
      obtained here from elderly subjects are limited and have to be interpreted with
      caution. Additional research on elderly specific assessment tools is needed.

PMID- 23012226
TI  - Microcystin-LR induces cytotoxicity and affects carp immune cells by impairment
      of their phagocytosis and the organization of the cytoskeleton.
AB  - Microcystin-LR (MC-LR) is the main isoform of hepatotoxin produced by
      cyanobacteria, which occur worldwide in the aquatic environment. The present
      study investigated the in vitro toxic MC-LR effects on immune cells isolated from
      the blood of carp. Cells were exposed to different MC-LR concentrations ranging
      from 0.01 to 1 ug ml(-1) for 2, 6 and 24 h. In addition, the effect of the toxin
      on the phagocytic activity of leukocytes and on actin and tubulin re-organization
      in phagocytic cells was studied. We observed that MC-LR induces apoptosis in
      lymphocytes 2 h after incubation, whereas high toxin concentrations induced
      necrosis in lymphocytes in a time- and concentration-dependent manner. Incubation
      of the cells for 2 h with 0.1 and 1 ug ml(-1) MC-LR inhibited phagocytosis
      without affecting apoptosis or glutathione (GSH) levels. Moreover, at this time
      point and with these concentrations, the toxin also induced a significant re
      organization of the actin cytoskeleton in phagocytes, which subsequently
      collapsed around the nucleus leading to cell shrinkage and the disappearance of
      filopodia. These results suggest that both phagocytes and lymphocytes are targets
      for MC-LR and the disturbances of phagocytosis may impair the balance of the
      immune system.

PMID- 23012227
TI  - An in situ carbonaceous mesoporous template for the synthesis of hierarchical ZSM
      5 zeolites by one-pot steam-assisted crystallization.
AB  - Blackened catalyst: Zeolites with large external surface area and mesopore volume
      were synthesized by a one-pot templating strategy, in which the crystallization
      proceeded concurrently with in situ carbonization templating to produce a
      mesoporous structure. The hierarchical materials exhibited superior catalytic
      performance over conventional zeolites in Friedel-Crafts acylation of anisole.

PMID- 23012229
TI  - Methyl ricinoleate as platform chemical for simultaneous production of fine
      chemicals and polymer precursors.
AB  - The modification of methyl ricinoleate by etherification of the hydroxyl group
      was accomplished by using a nonclassical ruthenium-catalyzed allylation reaction
      and also by esterification. Methyl ricinoleate derivatives were engaged in ring
      closing metathesis (RCM) reactions leading to biosourced 3,6-dihydropyran and
      alpha,beta-unsaturated lactone derivatives with concomitant production of polymer
      precursors. Sequential RCM/hydrogenation and RCM/cross-metathesis were also
      implemented as a straightforward method for the synthesis of tetrahydropyran and
      lactone derivatives as well as valuable monomers (i.e., polyamide precursors).

PMID- 23012228
TI  - At last: erythropoietin as a single glycoform.

PMID- 23012231
TI  - Unconventional reactivity of imidazolylidene pyridylidene ligands in iridium(III)
      and rhodium(III) complexes.

PMID- 23012230
TI  - Patterns of genomic aberrations suggest that Burkitt lymphomas with complex
      karyotype are distinct from other aggressive B-cell lymphomas with MYC
      rearrangement.
AB  - We previously showed that complex karyotypes (CK) and chromosome 13q
      abnormalities have an adverse prognostic impact in childhood Burkitt
      lymphomas/leukemias (BL) and diffuse large B-cell lymphomas (DLBCL). The aim of
      our study was to identify recurrent alterations associated with MYC
      rearrangements in aggressive B-cell lymphomas with CK. Multicolor fluorescence in
      situ hybridization (M-FISH) was performed in 84 patient samples (59 adults and 25
      children), including 37 BL (13 lymphomas and 24 acute leukemias), 12 DLBCL, 28 B
      cell lymphomas with intermediate features (DLBCL/BL), 4 B-cell precursor acute
      lymphoblastic leukemias (BCP-ALL), and 3 unclassifiable B-cell lymphomas. New
      (cytogenetically undetected) abnormalities were identified in 80% of patients. We
      also refined one-third of the chromosomal aberrations detected by karyotyping. M
      FISH proved to be more useful in identifying chromosomal partners involved in
      unbalanced translocations and in revealing greater complexity of 13q
      rearrangements. Most of the newly identified or refined recurrent alterations
      involved 1q, 13q and 3q (gains/losses), 7q and 18q (gains), or 6q (losses),
      suggesting that these secondary aberrations may play a role in lymphomagenesis.
      Several patterns of genomic aberrations were identified: 1q gains in BL,
      trisomies 7 in DLBCL, and 18q-translocations in adult non-BL. BCP-ALL usually
      displayed an 18q21 rearrangement. BL karyotypes were less complex and aneuploid
      than those of other MYC-rearranged lymphomas. BCP-ALL and DLBCL/BL were
      associated with a higher rate of early death than BL and DLBCL. These findings
      support the categorization of DLBCL/BL as a distinct entity and suggest that BL
      with CK are indeed different from other aggressive MYC-rearranged lymphomas,
      which usually show greater genetic complexity. (c) 2012 Wiley Periodicals, Inc.

PMID- 23012232
TI  - Phosphoinositides and cytokinesis: the "PIP" of the iceberg.
AB  - Phosphoinositides [Phosphatidylinositol (PtdIns), phosphatidylinositol 3
      monophosphate (PtdIns3P), phosphatidylinositol 4-monophosphate (PtdIns4P),
      phosphatidylinositol 5-monophosphate (PtdIns5P), phosphatidylinositol 3,4
      bisphosphate (PtdIns(3,4)P(2) ), phosphatidylinositol 3,5-bisphosphate
      (PtdIns(3,5)P(2) ), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2) ), and
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3) )] are lowly abundant
      acidic lipids found at the cytosolic leaflet of the plasma membrane and
      intracellular membranes. Initially discovered as precursors of second messengers
      in signal transduction, phosphoinositides are now known to directly or indirectly
      control key cellular functions, such as cell polarity, cell migration, cell
      survival, cytoskeletal dynamics, and vesicular traffic. Phosphoinositides
      actually play a central role at the interface between membranes and cytoskeletons
      and contribute to the identity of the cellular compartments by recruiting
      specific proteins. Increasing evidence indicates that several phosphoinositides,
      particularly PtdIns(4,5)P(2) , are essential for cytokinesis, notably after
      furrow ingression. The present knowledge about the specific phosphoinositides and
      phosphoinositide modifying-enzymes involved in cytokinesis will be first
      presented. The review of the current data will then show that furrow stability
      and cytokinesis abscission require that both phosphoinositide production and
      hydrolysis are regulated in space and time. Finally, I will further discuss
      recent mechanistic insights on how phosphoinositides regulate membrane
      trafficking and cytoskeletal remodeling for successful furrow ingression and
      intercellular bridge abscission. This will highlight unanticipated connections
      between cytokinesis and enzymes implicated in human diseases, such as the Lowe
      syndrome.

PMID- 23012233
TI  - High frequency of MYC gene amplification is a common feature of radiation-induced
      sarcomas. Further results from EORTC STBSG TL 01/01.
AB  - Irradiation is a major causative factor among the small subgroup of sarcomas with
      a known etiology. The prognosis of radiation-induced sarcomas (RIS) is
      significantly worse than that of their spontaneous counterparts. The most
      frequent histological subtypes include undifferentiated pleomorphic sarcomas,
      angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in
      radiation-induced angiosarcomas, but not in primary angiosarcomas, has recently
      been described. To investigate whether MYC amplifications are also frequent in
      RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS
      and 192 sporadic sarcomas by fluorescence in situ hybridization. We found
      significantly higher numbers of MYC amplifications in RIS than in sporadic
      sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic
      sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC
      amplifications were particularly frequent and always high level, while other RIS
      showed low-level amplifications. We conclude that MYC amplifications are a
      frequent feature of RIS as a group and may contribute to the biology of these
      tumors.

PMID- 23012234
TI  - Synthesis of five- and six-membered benzocyclic ketones through intramolecular
      alkene hydroacylation catalyzed by nickel(0)/N-heterocyclic carbenes.

PMID- 23012236
TI  - Human plasma protein polymorphisms and the persistence of cultural diversity.

PMID- 23012235
TI  - Regulation of integrin trafficking, cell adhesion, and cell migration by WASH and
      the Arp2/3 complex.
AB  - WASH is a nucleation-promoting factor for the Arp2/3 complex that is implicated
      in multiple endocytic trafficking pathways including receptor recycling, cargo
      degradation, and retromer-mediated receptor retrieval. We sought to examine
      whether WASH plays an important role in trafficking of specialized cargo
      molecules such as integrins, for which trafficking is highly regulated during
      cell migration. We observed that subdomains of early/sorting endosomes associated
      with dynamic WASH and filamentous actin, and alpha5-integrins trafficked through
      this population of endosomes. Depletion of WASH caused accumulation of alpha5
      integrins in intracellular compartments, reduction of alpha5-integrin
      localization at focal adhesions, and reduction in focal adhesion number.
      Transport of alpha5-integrins from internal endocytic structures to focal
      adhesions was disrupted upon WASH depletion or Arp2/3 complex inhibition.
      Furthermore, WASH-depleted cells displayed greatly reduced affinity for specific
      extracellular matrix proteins including fibronectin and impaired cell spreading
      ability. Interestingly, the reduced adhesion capacity of WASH-depleted cells
      resulted in their migrating more rapidly than control cells in wound healing
      assays. Our results define a requirement for WASH, Arp2/3 complex, and actin in
      specialized trafficking of integrins. These findings highlight a role for actin
      dynamics in influencing cell adhesion and migration via endocytic trafficking of
      integrins, in addition to the well-established role of actin in plasma membrane
      dynamics and contractility. (c) 2012 Wiley Periodicals, Inc.

PMID- 23012237
TI  - Structural and functional characterization of neuraminidase-like molecule N10
      derived from bat influenza A virus.
AB  - The recent discovery of the unique genome of influenza virus H17N10 in bats
      raises considerable doubt about the origin and evolution of influenza A viruses.
      It also identifies a neuraminidase (NA)-like protein, N10, that is highly
      divergent from the nine other well-established serotypes of influenza A NA (N1
      N9). The structural elucidation and functional characterization of influenza NAs
      have illustrated the complexity of NA structures, thus raising a key question as
      to whether N10 has a special structure and function. Here the crystal structure
      of N10, derived from influenza virus A/little yellow-shouldered
      bat/Guatemala/153/2009 (H17N10), was solved at a resolution of 2.20 A. Overall,
      the structure of N10 was found to be similar to that of the other known influenza
      NA structures. In vitro enzymatic assays demonstrated that N10 lacks canonical NA
      activity. A detailed structural analysis revealed dramatic alterations of the
      conserved active site residues that are unfavorable for the binding and cleavage
      of terminally linked sialic acid receptors. Furthermore, an unusual 150-loop
      (residues 147-152) was observed to participate in the intermolecular polar
      interactions between adjacent N10 molecules of the N10 tetramer. Our study of
      influenza N10 provides insight into the structure and function of the sialidase
      superfamily and sheds light on the molecular mechanism of bat influenza virus
      infection.

PMID- 23012238
TI  - Apo-intermediate in the transport cycle of lactose permease (LacY).
AB  - The lactose permease (LacY) catalyzes coupled stoichiometric symport of a
      galactoside and an H(+). Crystal structures reveal 12, mostly irregular,
      transmembrane alpha-helices surrounding a cavity with sugar- and H(+)- binding
      sites at the apex, which is accessible from the cytoplasm and sealed on the
      periplasmic side (an inward-facing conformer). An outward-facing model has also
      been proposed based on biochemical and spectroscopic measurements, as well as the
      X-ray structure of a related symporter. Converging lines of evidence demonstrate
      that LacY functions by an alternating access mechanism. Here, we generate a model
      for an apo-intermediate of LacY based on crystallographic coordinates of LacY and
      the oligopeptide/H(+) symporter. The model exhibits a conformation with an
      occluded cavity inaccessible from either side of the membrane. Furthermore,
      kinetic considerations and double electron-electron resonance measurements
      suggest that another occluded conformer with bound sugar exists during turnover.
      An energy profile for symport is also presented.

PMID- 23012239
TI  - Emergent states in heavy-electron materials.
AB  - We obtain the conditions necessary for the emergence of various low-temperature
      ordered states (local-moment antiferromagnetism, unconventional
      superconductivity, quantum criticality, and Landau Fermi liquid behavior) in
      Kondo lattice materials by extending the two-fluid phenomenological theory of
      heavy-electron behavior to incorporate the concept of hybridization
      effectiveness. We use this expanded framework to present a new phase diagram and
      consistent physical explanation and quantitative description of measured emergent
      behaviors such as the pressure variation of the onset of local-moment
      antiferromagnetic ordering at T(N), the magnitude of the ordered moment, the
      growth of superconductivity within that ordered state, the location of a quantum
      critical point, and of a delocalization line in the pressure/temperature phase
      diagram at which local moments have disappeared and the heavy-electron Fermi
      surface has grown to its maximum size. We apply our model to CeRhIn(5) and a
      number of other heavy-electron materials and find good agreement with experiment.

PMID- 23012241
TI  - Vacancy-stabilized crystalline order in hard cubes.
AB  - We examine the effect of vacancies on the phase behavior and structure of systems
      consisting of hard cubes using event-driven molecular dynamics and Monte Carlo
      simulations. We find a first-order phase transition between a fluid and a simple
      cubic crystal phase that is stabilized by a surprisingly large number of
      vacancies, reaching a net vacancy concentration of approximately 6.4% near bulk
      coexistence. Remarkably, we find that vacancies increase the positional order in
      the system. Finally, we show that the vacancies are delocalized and therefore
      hard to detect.

PMID- 23012240
TI  - Single-molecule imaging reveals target-search mechanisms during DNA mismatch
      repair.
AB  - The ability of proteins to locate specific targets among a vast excess of
      nonspecific DNA is a fundamental theme in biology. Basic principles governing
      these search mechanisms remain poorly understood, and no study has provided
      direct visualization of single proteins searching for and engaging target sites.
      Here we use the postreplicative mismatch repair proteins MutSalpha and MutLalpha
      as model systems for understanding diffusion-based target searches. Using single
      molecule microscopy, we directly visualize MutSalpha as it searches for DNA
      lesions, MutLalpha as it searches for lesion-bound MutSalpha, and the
      MutSalpha/MutLalpha complex as it scans the flanking DNA. We also show that
      MutLalpha undergoes intersite transfer between juxtaposed DNA segments while
      searching for lesion-bound MutSalpha, but this activity is suppressed upon
      association with MutSalpha, ensuring that MutS/MutL remains associated with the
      damage-bearing strand while scanning the flanking DNA. Our findings highlight a
      hierarchy of lesion- and ATP-dependent transitions involving both MutSalpha and
      MutLalpha, and help establish how different modes of diffusion can be used during
      recognition and repair of damaged DNA.

PMID- 23012243
TI  - The frequency of previously undetectable deletions involving 3' Exons of the PMS2
      gene.
AB  - Lynch syndrome is characterized by mutations in one of four mismatch repair
      genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes
      includes sequencing of exonic regions and deletion/duplication analysis. However,
      detection of deletions and duplications in PMS2 has previously been confined to
      Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the
      remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method
      that permits detection of deletions of PMS2 Exons 12-15; however, the frequency
      of such deletions has not yet been determined. To address this question, we
      tested for 3' deletions in 58 samples that were reported to be negative for PMS2
      mutations using previously available methods. All samples were from individuals
      whose tumors exhibited loss of PMS2 immunohistochemical staining without
      concomitant loss of MLH1 immunostaining. We identified seven samples in this
      cohort with deletions in the 3' region of PMS2, including three previously
      reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15.
      Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples).
      Breakpoint analysis of the intragenic deletions suggests they occurred through
      Alu-mediated recombination. Our results indicate that ~12% of samples suspected
      of harboring a PMS2 mutation based on immunohistochemical staining, for which
      mutations have not yet been identified, would benefit from testing using the new
      methodology.

PMID- 23012244
TI  - Literature reviews as a research strategy.

PMID- 23012245
TI  - Inhibiting aurora kinases reduces tumor growth and suppresses tumor recurrence
      after chemotherapy in patient-derived triple-negative breast cancer xenografts.
AB  - Triple-negative breast cancers (TNBC) have an aggressive phenotype with a
      relatively high rate of recurrence and poor overall survival. To date, there is
      no approved targeted therapy for TNBCs. Aurora kinases act as regulators of
      mammalian cell division. They are important for cell-cycle progression and are
      frequently overexpressed or mutated in human tumors, including breast cancer. In
      this study, we investigated the therapeutic potential of targeting Aurora kinases
      in preclinical models of human breast cancers using a pan-inhibitor of Aurora
      kinases, AS703569. In vitro, AS703569 was tested in 15 human breast cancer cell
      lines. TNBC cell lines were more sensitive to AS703569 than were other types of
      breast cancer cells. Inhibition of proliferation was associated with cell-cycle
      arrest, aneuploidy, and apoptosis. In vivo, AS703569 administered alone
      significantly inhibited tumor growth in seven of 11 patient-derived breast cancer
      xenografts. Treatment with AS703569 was associated with a decrease of phospho
      histone H3 expression. Finally, AS703569 combined to doxorubicin-cyclophosphamide
      significantly inhibited in vivo tumor recurrence, suggesting that Aurora kinase
      inhibitors could be used both in monotherapy and in combination settings. In
      conclusion, these data indicate that targeting Aurora kinases could represent a
      new effective approach for TNBC treatment.

PMID- 23012246
TI  - RSK2(Ser227) at N-terminal kinase domain is a potential therapeutic target for
      multiple myeloma.
AB  - Multiple myeloma is an entity of cytogenetically and genetically heterogenous
      plasma cell neoplasms. Despite recent improvement in the treatment outcome of
      multiple myeloma by novel molecular-targeted chemotherapeutics, multiple myeloma
      remains incurable. The identification of a therapeutic target molecule in which
      various signaling for cell-survival converge is a core component for the
      development of new therapeutic strategies against multiple myeloma. RSK2 is an
      essential mediator of the ERK1/2 signaling pathway for cell survival and
      proliferation. In this study, we discovered that RSK2(Ser227), which is located
      at the N-terminal kinase domain and is one site responsible for substrate
      phosphorylation, is activated through phosphorylation regardless of the type of
      cytogenetic abnormalities or upstream molecular signaling in all 12 multiple
      myeloma-derived cell lines examined and 6 of 9 patient-derived CD138-positive
      primary myeloma cells. The chemical inhibition of RSK2(Ser227) by BI-D1870 or
      gene knockdown of RSK2 inhibits myeloma cell proliferation through apoptosis
      induction, and this anti-myeloma effect was accompanied by downregulation of c
      MYC, cyclin D, p21(WAF1/CIP1), and MCL1. RSK2(Ser227) inhibition resulting from
      BI-D1870 treatment restored lenalidomide-induced direct cytotoxicity of myeloma
      cells from interleukin-6-mediated cell protection, showed no cross-resistance to
      bortezomib, and exerted additive/synergistic antiproliferative effects in
      conjunction with the mTOR, histone deacetylase, and BH3-mimicking BCL2/BCLX(L)
      inhibitors. These results suggest that RSK2(Ser227) is a potential therapeutic
      target not only for newly diagnosed but also for patients with later phase
      multiple myeloma who are resistant or refractory to currently available anti
      myeloma therapies.

PMID- 23012247
TI  - Targeting the inhibitor of apoptosis proteins as a novel therapeutic strategy in
      medulloblastoma.
AB  - Medulloblastoma is the most common malignant brain tumor of childhood. Novel
      therapeutic strategies are urgently needed to overcome cytotoxic resistance. We
      hypothesized that antiapoptotic signals contribute to resistance and that
      treatment with proapoptotic agents could increase the efficacy of conventional
      therapies. A PCR array was used to assess the status of the apoptotic signaling
      pathway in medulloblastoma cells after treatment with cytotoxic chemotherapy.
      Treatment with cisplatin led to the upregulation of antiapoptotic signals,
      including inhibitor of apoptosis proteins (IAP), in medulloblastoma cells. We
      subsequently investigated the synergistic effect of a small-molecule IAP
      inhibitor, LBW242, in combination with cisplatin and/or radiotherapy in three
      human medulloblastoma cell lines and 5 short term primary patient medulloblastoma
      cultures. The addition of LBW242 to chemotherapy resulted in significantly
      increased antitumor activity with a similar effect observed in combination with
      radiotherapy. Measurement of caspase-8 and -9 activity indicated that the synergy
      resulted from induction of both the intrinsic and extrinsic apoptotic pathways.
      Apoptosis was confirmed by Annexin V staining and activation of caspases 3/7.
      Xenograft models were used to evaluate the mechanism of action and efficacy in
      vivo. The combination therapy significantly reduced the tumor burden in a
      medulloblastoma xenograft model and TUNEL analysis in a medulloblastoma
      orthograft confirmed in vivo induction of apoptosis. These findings support the
      strategy of targeting IAPs in combination with cytotoxic therapy as a novel
      treatment strategy for patients with medulloblastoma.

PMID- 23012248
TI  - Targeting KRAS-mutant non-small cell lung cancer with the Hsp90 inhibitor
      ganetespib.
AB  - Mutant KRAS is a feature of more than 25% of non-small cell lung cancers (NSCLC)
      and represents one of the most prevalent oncogenic drivers in this disease. NSCLC
      tumors with oncogenic KRAS respond poorly to current therapies, necessitating the
      pursuit of new treatment strategies. Targeted inhibition of the molecular
      chaperone Hsp90 results in the coordinated blockade of multiple oncogenic
      signaling pathways in tumor cells and has thus emerged as an attractive avenue
      for therapeutic intervention in human malignancies. Here, we examined the
      activity of ganetespib, a small-molecule inhibitor of Hsp90 currently in clinical
      trials for NSCLCs in a panel of lung cancer cell lines harboring a diverse
      spectrum of KRAS mutations. In vitro, ganetespib was potently cytotoxic in all
      lines, with concomitant destabilization of KRAS signaling effectors. Combinations
      of low-dose ganetespib with MEK or PI3K/mTOR inhibitors resulted in superior
      cytotoxic activity than single agents alone in a subset of mutant KRAS cells, and
      the antitumor efficacy of ganetespib was potentiated by cotreatment with the
      PI3K/mTOR inhibitor BEZ235 in A549 xenografts in vivo. At the molecular level,
      ganetespib suppressed activating feedback signaling loops that occurred in
      response to MEK and PI3K/mTOR inhibition, although this activity was not the sole
      determinant of combinatorial benefit. In addition, ganetespib sensitized mutant
      KRAS NSCLC cells to standard-of-care chemotherapeutics of the antimitotic,
      topoisomerase inhibitor, and alkylating agent classes. Taken together, these data
      underscore the promise of ganetespib as a single-agent or combination treatment
      in KRAS-driven lung tumors.

PMID- 23012249
TI  - Increased neutrophil oxidative burst metabolism in systemic lupus erythematosus.
AB  - INTRODUCTION: There is increased frequency of discoid lesions (2.7%) and SLE
      (0.5%) in patients with chronic granulomatosus disease, but the literature is
      still controversial about phagocyte oxidative burst in SLE patients. MATERIALS
      AND METHODS: 300 SLE patients and 301 blood donors were evaluated for
      quantitation of the oxidative burst in phagocytes by flow cytometry based on the
      oxidation of 2,7-dichlorofluorescein-diacetate after stimuli with Staphylococcus
      aureus and Pseudomonas aeruginosa. RESULTS: Neutrophils from SLE patients
      displayed higher basal reactive oxygen species (ROS) production than healthy
      controls [Mean of fluorescence intensity (MFI) = 53.77 +/- 11.38 vs 15.08 +/-
      2.63, p < 0.001] and after stimulation with S. aureus (MFI = 355.46 +/- 58.55 vs
      151.92 +/- 28.25, p < 0.001) or P. aeruginosa (MFI = 82.53 +/- 10.1 vs 48.99 +/-
      6.74, p < 0.001). There was stronger neutrophil response after bacterial stimuli
      (DeltaMFI) in SLE patients than in healthy controls (S. aureus = 301.69 +/- 54.42
      vs 118.38 +/- 26.03, p < 0.001; P. aeruginosa = 28.76 +/- 12.3 vs 15.45 +/- 5.15,
      p < 0.001), but no difference with respect to the oxidative burst profile
      according to disease activity (SLEDAI >= 6) or severity (SLICC-DI >=2). Patients
      with kidney involvement presented higher basal and stimulated ROS production in
      neutrophils. DISCUSSION: The present findings corroborate the important role of
      innate immunity in SLE and implicate neutrophils in the pathophysiology of the
      disease.

PMID- 23012251
TI  - Expanded functional coupling of subcortical nuclei with the motor resting-state
      network in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) impairs signal transmission along cortico
      cortical and cortico-subcortical connections, affecting functional integration
      within the motor network. Functional magnetic resonance imaging (fMRI) during
      motor tasks has revealed altered functional connectivity in MS, but it is unclear
      how much motor disability contributed to these abnormal functional interaction
      patterns. OBJECTIVE: To avoid any influence of impaired task performance, we
      examined disease-related changes in functional motor connectivity in MS at rest.
      METHODS: A total of 42 patients with MS and 30 matched controls underwent a 20
      minute resting-state fMRI session at 3 Tesla. Independent component analysis was
      applied to the fMRI data to identify disease-related changes in motor resting
      state connectivity. RESULTS: Patients with MS showed a spatial expansion of motor
      resting-state connectivity in deep subcortical nuclei but not at the cortical
      level. The anterior and middle parts of the putamen, adjacent globus pallidus,
      anterior and posterior thalamus and the subthalamic region showed stronger
      functional connectivity with the motor network in the MS group compared with
      controls. CONCLUSION: MS is characterised by more widespread motor connectivity
      in the basal ganglia while cortical motor resting-state connectivity is
      preserved. The expansion of subcortical motor resting-state connectivity in MS
      indicates less efficient funnelling of neural processing in the executive motor
      cortico-basal ganglia-thalamo-cortical loops.

PMID- 23012250
TI  - Sex influences immune responses to viruses, and efficacy of prophylaxis and
      treatments for viral diseases.
AB  - The intensity and prevalence of viral infections are typically higher in males,
      whereas disease outcome can be worse for females. Females mount higher innate and
      adaptive immune responses than males, which can result in faster clearance of
      viruses, but also contributes to increased development of immunopathology. In
      response to viral vaccines, females mount higher antibody responses and
      experience more adverse reactions than males. The efficacy of antiviral drugs at
      reducing viral load differs between the sexes, and the adverse reactions to
      antiviral drugs are typically greater in females than males. Several variables
      should be considered when evaluating male/female differences in responses to
      viral infection and treatment: these include hormones, genes, and gender-specific
      factors related to access to, and compliance with, treatment. Knowledge that the
      sexes differ in their responses to viruses and to treatments for viral diseases
      should influence the recommended course of action differently for males and
      females. Editor's suggested further reading in BioEssays X-chromosome-located
      microRNAs in immunity: Might they explain male/female differences Abstract.

PMID- 23012252
TI  - Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and
      neuromyelitis optica.
AB  - BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are immune
      mediated inflammatory diseases of the central nervous system. In the acute phase
      of these diseases, secondary ischemia due to inflammation-induced endothelial
      dysfunction may be an important pathological change. Pentraxin 3 (PTX3) is a pro
      inflammatory protein and a novel biomarker of inflammatory vascular diseases.
      OBJECTIVE: We aimed to determine whether PTX3 levels are elevated in MS and NMO
      patients. METHODS: The concentrations of plasma PTX3 were measured using an
      enzyme-linked immunosorbent assay in 22 MS patients, 26 NMO patients, 15 acute
      cerebral infarction (CI) patients, 11 mild headache patients, and 14 volunteer
      controls. RESULTS: During relapse, plasma PTX3 levels were higher in MS patients
      than in headache patients (p=0.003) and controls (p<0.001). Plasma PTX3 levels
      were also increased in NMO patients compared with CI patients (p=0.011), headache
      patients (p<0.001) and controls (p<0.001). CI patients showed elevated PTX3
      levels compared with controls (p=0.008). MS and NMO patients showed a trend
      toward an increased disease disability with higher plasma PTX3 during relapse
      (MS: p=0.005; NMO: p<0.001). Plasma PTX3 levels were remarkably lower in
      remission than in the relapse stage (MS: p<0.001; NMO: p<0.001). CONCLUSION:
      Plasma PTX3 level is associated with inflammatory responses in MS and NMO.

PMID- 23012253
TI  - Scoring treatment response in patients with relapsing multiple sclerosis.
AB  - BACKGROUND: We employed clinical and magnetic resonance imaging (MRI) measures in
      combination, to assess patient responses to interferon in multiple sclerosis.
      OBJECTIVE: To optimize and validate a scoring system able to discriminate
      responses to interferon treatment in patients with relapsing-remitting multiple
      sclerosis (RRMS). METHODS: Our analysis included two large, independent datasets
      of RRMS patients who were treated with interferons that included 4-year follow-up
      data. The first dataset ("training set") comprised of 373 RRMS patients from a
      randomized clinical trial of subcutaneous interferon beta-1a. The second
      ("validation set") included an observational cohort of 222 RRMS patients treated
      with different interferons. The new scoring system, a modified version of that
      previously proposed by Rio et al., was first tested on the training set, then
      validated using the validation set. The association between disability
      progression and risk group, as defined by the score, was evaluated by Kaplan
      Meier survival curves and Cox regression, and quantified by hazard ratios (HRs).
      RESULTS: The score (0-3) was based on the number of new T2 lesions (>5) and
      clinical relapses (0,1 or 2) during the first year of therapy. The risk of
      disability progression increased with higher scores. In the validation set,
      patients with score of 0 showed a 3-year progression probability of 24%, while
      those with a score of 1 increased to 33% (HR = 1.56; p = 0.13), and those with
      score greater than or equal to 2 increased to 65% (HR = 4.60; p < 0.001).
      CONCLUSIONS: We report development of a simple, quantitative and complementary
      tool for predicting responses in interferon-treated patients that could help
      clinicians make treatment decisions.

PMID- 23012254
TI  - Improved ability to work after one year of natalizumab treatment in multiple
      sclerosis. Analysis of disease-specific and work-related factors that influence
      the effect of treatment.
AB  - BACKGROUND: Multiple sclerosis (MS) constitutes one of the major diseases that
      leads to neurological impairment and as a consequence also reduces ability to
      work. OBJECTIVES: The purpose of this study was to analyze possible effects on
      work ability resulting from highly active anti-inflammatory treatment in MS.
      METHODS: We analyzed the effects of introducing an anti-inflammatory treatment,
      natalizumab, in MS, on factors related to work ability. This was done through a
      comprehensive questionnaire distributed to all patients in Sweden starting on
      natalizumab treatment between June 2007 and May 2008, identified via the Swedish
      National MS registry. RESULTS: MS patients who were receiving sickness benefit
      and were treated with natalizumab approximately doubled their working ability in
      relation to their total employment rate. We also documented a significant
      improvement of their ability to cope with work-related requirements after one
      year of natalizumab treatment, an improvement which was independent of the
      previous level of employment. Predictors of a positive effect on work ability
      were short disease duration, younger age and lower Expanded Disability Status
      Scale (EDSS) grade at treatment onset. CONCLUSIONS: Our data support the notion
      that early inflammatory control in MS is essential to preserve a healthy state in
      MS that counteracts the negative consequences of the disease both at a personal
      and at a societal level.

PMID- 23012255
TI  - ESMO Consensus Guidelines for management of patients with colon and rectal
      cancer. a personalized approach to clinical decision making.
AB  - Colorectal cancer (CRC) is the most common tumour type in both sexes combined in
      Western countries. Although screening programmes including the implementation of
      faecal occult blood test and colonoscopy might be able to reduce mortality by
      removing precursor lesions and by making diagnosis at an earlier stage, the
      burden of disease and mortality is still high. Improvement of diagnostic and
      treatment options increased staging accuracy, functional outcome for early stages
      as well as survival. Although high quality surgery is still the mainstay of
      curative treatment, the management of CRC must be a multi-modal approach
      performed by an experienced multi-disciplinary expert team. Optimal choice of the
      individual treatment modality according to disease localization and extent,
      tumour biology and patient factors is able to maintain quality of life, enables
      long-term survival and even cure in selected patients by a combination of
      chemotherapy and surgery. Treatment decisions must be based on the available
      evidence, which has been the basis for this consensus conference-based guideline
      delivering a clear proposal for diagnostic and treatment measures in each stage
      of rectal and colon cancer and the individual clinical situations. This ESMO
      guideline is recommended to be used as the basis for treatment and management
      decisions.

PMID- 23012256
TI  - Calibration and use of the polar organic chemical integrative sampler--a critical
      review.
AB  - The implementation of strict environmental quality standards for polar organic
      priority pollutants poses a challenge for monitoring programs. The polar organic
      chemical integrative sampler (POCIS) may help to address the challenge of
      measuring low and fluctuating trace concentrations of such organic contaminants,
      offering significant advantages over traditional sampling. In the present review,
      the authors evaluate POCIS calibration methods and factors affecting sampling
      rates together with reported environmental applications. Over 300 compounds have
      been shown to accumulate in POCIS, including pesticides, pharmaceuticals,
      hormones, and industrial chemicals. Polar organic chemical integrative sampler
      extracts have been used for both chemical and biological analyses. Several
      different calibration methods have been described, which makes it difficult to
      directly compare sampling rates. In addition, despite the fact that some attempts
      to correlate sampling rates with the properties of target compounds such as log
      K(OW) have been met with varying success, an overall model that can predict
      uptake is lacking. Furthermore, temperature, water flow rates, salinity, pH, and
      fouling have all been shown to affect uptake; however, there is currently no
      robust method available for adjusting for these differences. Overall, POCIS has
      been applied to a wide range of sampling environments and scenarios and has been
      proven to be a useful screening tool. However, based on the existing literature,
      a more mechanistic approach is required to increase understanding and thus
      improve the quantitative nature of the measurements.

PMID- 23012258
TI  - Empirical Bayes correction for the Winner's Curse in genetic association studies.
AB  - We consider an Empirical Bayes method to correct for the Winner's Curse
      phenomenon in genome-wide association studies. Our method utilizes the collective
      distribution of all odds ratios (ORs) to determine the appropriate correction for
      a particular single-nucleotide polymorphism (SNP). We can show that this approach
      is squared error optimal provided that this collective distribution is accurately
      estimated in its tails. To improve the performance when correcting the OR
      estimates for the most highly associated SNPs, we develop a second estimator that
      adaptively combines the Empirical Bayes estimator with a previously considered
      Conditional Likelihood estimator. The applications of these methods to both
      simulated and real data suggest improved performance in reducing selection bias.

PMID- 23012257
TI  - DCPIB, the proposed selective blocker of volume-regulated anion channels,
      inhibits several glutamate transport pathways in glial cells.
AB  - 4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB)
      was identified as the selective blocker of volume-regulated anion channels
      (VRAC). VRAC are permeable to small inorganic and organic anions, including the
      excitatory neurotransmitter glutamate. In recent years DCPIB has been
      increasingly used for probing the physiologic and pathologic roles of VRAC and
      was found to potently suppress pathologic glutamate release in cerebral ischemia.
      Because ischemic glutamate release can be mediated by a plethora of mechanisms,
      in this study we explored the selectivity of DCPIB toward the majority of
      previously identified glutamate transporters and permeability pathways. l
      [(3)H]glutamate, d-[(3)H]aspartate, and l-[(14)C]cystine were used to trace amino
      acid release and uptake. We found that in addition to its well-characterized
      effect on VRAC, DCPIB potently inhibited glutamate release via connexin
      hemichannels and glutamate uptake via the glutamate transporter GLT-1 in rat
      glial cells. In contrast, DCPIB had no direct effect on vesicular glutamate
      release from rat brain synaptosomes or the cystine/glutamate exchange in
      astrocytes. The compound did not affect the astrocytic glutamate transporter
      GLAST, nor did it block glutamate release via the P2X(7)/pannexin permeability
      pathway. The ability of DCPIB to directly block connexin hemichannels was
      confirmed using a gene-specific siRNA knockdown approach. Overall, our data
      demonstrate that DCPIB influences several glutamate transport pathways and that
      its effects on VRAC in vivo should be verified using additional pharmacological
      controls.

PMID- 23012259
TI  - Commentary: is robotic thyroid surgery worth the learning curve?
AB  - There are numerous potential applications of robotic technology to head and neck
      procedures, including thyroidectomy. The learning curve for robotic thyroid
      surgery appears to be steep, as highlighted in a study published in this issue.
      This commentary explores the challenges with learning robotic thyroid surgery and
      questions the potential risks and benefits of increased adoption of this
      approach.

PMID- 23012260
TI  - Aberrant facial nerve exposed behind the eardrum.

PMID- 23012261
TI  - Heterogeneous ensemble approach with discriminative features and modified
      SMOTEbagging for pre-miRNA classification.
AB  - An ensemble classifier approach for microRNA precursor (pre-miRNA) classification
      was proposed based upon combining a set of heterogeneous algorithms including
      support vector machine (SVM), k-nearest neighbors (kNN) and random forest (RF),
      then aggregating their prediction through a voting system. Additionally, the
      proposed algorithm, the classification performance was also improved using
      discriminative features, self-containment and its derivatives, which have shown
      unique structural robustness characteristics of pre-miRNAs. These are applicable
      across different species. By applying preprocessing methods--both a correlation
      based feature selection (CFS) with genetic algorithm (GA) search method and a
      modified-Synthetic Minority Oversampling Technique (SMOTE) bagging rebalancing
      method--improvement in the performance of this ensemble was observed. The overall
      prediction accuracies obtained via 10 runs of 5-fold cross validation (CV) was
      96.54%, with sensitivity of 94.8% and specificity of 98.3%-this is better in
      trade-off sensitivity and specificity values than those of other state-of-the-art
      methods. The ensemble model was applied to animal, plant and virus pre-miRNA and
      achieved high accuracy, >93%. Exploiting the discriminative set of selected
      features also suggests that pre-miRNAs possess high intrinsic structural
      robustness as compared with other stem loops. Our heterogeneous ensemble method
      gave a relatively more reliable prediction than those using single classifiers.
      Our program is available at http://ncrna-pred.com/premiRNA.html.

PMID- 23012262
TI  - Transcriptional activation of yeast genes disrupts intragenic nucleosome phasing.
AB  - Nucleosomes often undergo extensive rearrangement when genes are activated for
      transcription. We have shown previously, using paired-end sequencing of yeast
      nucleosomes, that major changes in chromatin structure occur when genes are
      activated by 3-aminotriazole (3AT), an inducer of the transcriptional activator
      Gcn4. Here, we provide a global analysis of these data. At the genomic level,
      nucleosomes are regularly phased relative to the transcription start site.
      However, for a subset of 234 strongly induced genes, this phasing is much more
      irregular after induction, consistent with the loss of some nucleosomes and the
      re-positioning of the remaining nucleosomes. To address the nature of this
      rearrangement, we developed the inter-nucleosome distance auto-correlation (DAC)
      function. At long range, DAC analysis indicates that nucleosomes have an average
      spacing of 162 bp, consistent with the reported repeat length. At short range,
      DAC reveals a 10.25-bp periodicity, implying that nucleosomes in overlapping
      positions are rotationally related. DAC analysis of the 3AT-induced genes
      suggests that transcription activation coincides with rearrangement of
      nucleosomes into irregular arrays with longer spacing. Sequence analysis of the
      +1 nucleosomes belonging to the 45 most strongly activated genes reveals a
      distinctive periodic oscillation in the A/T-dinucleotide occurrence that is
      present throughout the nucleosome and extends into the linker. This unusual
      pattern suggests that the +1 nucleosomes might be prone to sliding, thereby
      facilitating transcription.

PMID- 23012263
TI  - Noncoder: a web interface for exon array-based detection of long non-coding RNAs.
AB  - Due to recent technical developments, a high number of long non-coding RNAs
      (lncRNAs) have been discovered in mammals. Although it has been shown that
      lncRNAs are regulated differently among tissues and disease statuses, functions
      of these transcripts are still unknown in most cases. GeneChip Exon 1.0 ST Arrays
      (exon arrays) from Affymetrix, Inc. have been used widely to profile genome-wide
      expression changes and alternative splicing of protein-coding genes. Here, we
      demonstrate that re-annotation of exon array probes can be used to profile
      expressions of tens of thousands of lncRNAs. With this annotation, a detailed
      inspection of lncRNAs and their isoforms is possible. To allow for a general
      usage to the research community, we developed a user-friendly web interface
      called 'noncoder'. By uploading CEL files from exon arrays and with a few mouse
      clicks and parameter settings, exon array data will be normalized and analysed to
      identify differentially expressed lncRNAs. Noncoder provides the detailed
      annotation information of lncRNAs and is equipped with unique features to allow
      for an efficient search for interesting lncRNAs to be studied further. The web
      interface is available at http://noncoder.mpi-bn.mpg.de.

PMID- 23012264
TI  - Exploring polymorphisms in B-DNA helical conformations.
AB  - The traditional mesoscopic paradigm represents DNA as a series of base-pair steps
      whose energy response to equilibrium perturbations is elastic, with harmonic
      oscillations (defining local stiffness) around a single equilibrium conformation.
      In addition, base sequence effects are often analysed as a succession of
      independent XpY base-pair steps (i.e. a nearest-neighbour (NN) model with only 10
      unique cases). Unfortunately, recent massive simulations carried out by the ABC
      consortium suggest that the real picture of DNA flexibility may be much more
      complex. The paradigm of DNA flexibility therefore needs to be revisited. In this
      article, we explore in detail one of the most obvious violations of the elastic
      NN model of flexibility: the bimodal distributions of some helical parameters. We
      perform here an in-depth statistical analysis of a very large set of MD
      trajectories and also of experimental structures, which lead to very solid
      evidence of bimodality. We then suggest ways to improve mesoscopic models to
      account for this deviation from the elastic regime.

PMID- 23012265
TI  - The dynamics of Ku70/80 and DNA-PKcs at DSBs induced by ionizing radiation is
      dependent on the complexity of damage.
AB  - DNA double-strand breaks (DSBs) are biologically one of the most important
      cellular lesions and possess varying degrees of chemical complexity. The notion
      that the repairability of more chemically complex DSBs is inefficient led to the
      concept that the extent of DSB complexity underlies the severity of the
      biological consequences. The repair of DSBs by non-homologous end joining (NHEJ)
      has been extensively studied but it remains unknown whether more complex DSBs
      require a different sub-set of NHEJ protein for their repair compared with simple
      DSBs. To address this, we have induced DSBs in fluorescently tagged mammalian
      cells (Ku80-EGFP, DNA-PKcs-YFP or XRCC4-GFP, key proteins in NHEJ) using ultra
      soft X-rays (USX) or multi-photon near infrared (NIR) laser irradiation. We have
      shown in real-time that simple DSBs, induced by USX or NIR microbeam irradiation,
      are repaired rapidly involving Ku70/80 and XRCC4/Ligase IV/XLF. In contrast, DSBs
      with greater chemical complexity are repaired slowly involving not only Ku70/80
      and XRCC4/Ligase IV/XLF but also DNA-PKcs. Ataxia telangiectasia-mutated
      inhibition only retards repair of the more chemically complex DSBs which require
      DNA-PKcs. In summary, the repair of DSBs by NHEJ is highly regulated with pathway
      choice and kinetics of repair dependent on the chemical complexity of the DSB.

PMID- 23012266
TI  - Kinetic and thermodynamic characterization of the reaction pathway of box H/ACA
      RNA-guided pseudouridine formation.
AB  - The box H/ACA RNA-guided pseudouridine synthase is a complicated
      ribonucleoprotein enzyme that recruits substrate via both the guide RNA and the
      catalytic subunit Cbf5. Structural studies have revealed multiple conformations
      of the enzyme, but a quantitative description of the reaction pathway is still
      lacking. Using fluorescence correlation spectroscopy, we here measured the
      equilibrium dissociation constants and kinetic association and dissociation rates
      of substrate and product complexes mimicking various reaction intermediate
      states. These data support a sequential model for substrate loading and product
      release regulated by the thumb loop of Cbf5. The uridine substrate is first bound
      primarily through interaction with the guide RNA and then loaded into the active
      site while progressively interacted with the thumb. After modification, the
      subtle chemical structure change from uridine to pseudouridine at the target site
      triggers the release of the thumb, resulting in an intermediate complex with the
      product bound mainly by the guide RNA. By dissecting the role of Gar1 in
      individual steps of substrate turnover, we show that Gar1 plays a major role in
      catalysis and also accelerates product release about 2-fold. Our biophysical
      results integrate with previous structural knowledge into a coherent reaction
      pathway of H/ACA RNA-guided pseudouridylation.

PMID- 23012267
TI  - Intergenerational transmission of the reminiscence bump and biographical conflict
      knowledge.
AB  - In the study reported here, we investigated intergenerational transmission of
      life stories in two groups of young adults: a conflict group and a nonconflict
      group. Only participants in the conflict group had parents who lived through
      violent political upheaval. All participants recalled and dated 10 important
      events from one of their parents' lives. There were three main findings. First,
      both groups produced sets of events that displayed a reminiscence bump related to
      the parent's estimated age at the time of the event. Second, the majority of the
      events in both groups were transitions that were perceived to have exerted a
      significant psychological and material impact on a parent's life. Third, in the
      conflict group, 25% of recalled events were conflict related. This finding
      indicates that historical conflict knowledge is passed from one generation to the
      next and that it is understood to have had a personally relevant, life-altering
      effect. Moreover, the findings suggest that transitional impact and perceived
      importance help determine which events children will remember from a parent's
      life.

PMID- 23012268
TI  - Decay versus interference: a new look at an old interaction.

PMID- 23012269
TI  - Most reported genetic associations with general intelligence are probably false
      positives.
AB  - General intelligence (g) and virtually all other behavioral traits are heritable.
      Associations between g and specific single-nucleotide polymorphisms (SNPs) in
      several candidate genes involved in brain function have been reported. We sought
      to replicate published associations between g and 12 specific genetic variants
      (in the genes DTNBP1, CTSD, DRD2, ANKK1, CHRM2, SSADH, COMT, BDNF, CHRNA4, DISC1,
      APOE, and SNAP25) using data sets from three independent, well-characterized
      longitudinal studies with samples of 5,571, 1,759, and 2,441 individuals. Of 32
      independent tests across all three data sets, only 1 was nominally significant.
      By contrast, power analyses showed that we should have expected 10 to 15
      significant associations, given reasonable assumptions for genotype effect sizes.
      For positive controls, we confirmed accepted genetic associations for Alzheimer's
      disease and body mass index, and we used SNP-based calculations of genetic
      relatedness to replicate previous estimates that about half of the variance in g
      is accounted for by common genetic variation among individuals. We conclude that
      the molecular genetics of psychology and social science requires approaches that
      go beyond the examination of candidate genes.

PMID- 23012270
TI  - Grin and bear it: the influence of manipulated facial expression on the stress
      response.
AB  - In the study reported here, we investigated whether covertly manipulating
      positive facial expressions would influence cardiovascular and affective
      responses to stress. Participants (N = 170) naive to the purpose of the study
      completed two different stressful tasks while holding chopsticks in their mouths
      in a manner that produced a Duchenne smile, a standard smile, or a neutral
      expression. Awareness was manipulated by explicitly asking half of all
      participants in the smiling groups to smile (and giving the other half no
      instructions related to smiling). Findings revealed that all smiling
      participants, regardless of whether they were aware of smiling, had lower heart
      rates during stress recovery than the neutral group did, with a slight advantage
      for those with Duchenne smiles. Participants in the smiling groups who were not
      explicitly asked to smile reported less of a decrease in positive affect during a
      stressful task than did the neutral group. These findings show that there are
      both physiological and psychological benefits from maintaining positive facial
      expressions during stress.

PMID- 23012271
TI  - True love waits? A sibling-comparison study of age at first sexual intercourse
      and romantic relationships in young adulthood.
AB  - This study tested whether the timing of first sexual intercourse in adolescence
      predicts romantic outcomes in adulthood, including union formation, number of
      romantic partners, and relationship dissatisfaction. Participants were 1,659 same
      sex sibling pairs from the National Longitudinal Study of Adolescent Health, who
      were followed from adolescence (mean age = 16 years) to young adulthood (mean age
      = 29 years). The timing of participants' first sexual intercourse was classified
      as early (at age 14 or earlier), on time (between the ages of 15 and 19), or late
      (at age 19 or older). Compared with early and on-time age at first sex, late age
      at first sex was associated with decreased odds of marriage or nonmarital
      cohabitation and fewer romantic partners in adulthood. Among individuals who had
      married or cohabited with a partner, late timing of first sex was associated with
      significantly reduced levels of relationship dissatisfaction, even after
      controlling for genetic and environmental differences between families (using a
      sibling-comparison model), demographic outcomes in adulthood, and involvement in
      dating during adolescence. These results underscore the contribution of a life
      span approach to our understanding of romantic relationships.

PMID- 23012273
TI  - Thermoreversible gelation polymer as an embolic material for aneurysm treatment:
      a delivery device for dermal fibroblasts and basic fibroblast growing factor into
      experimental aneurysms in rats.
AB  - BACKGROUND: This study evaluates whether thermoreversible gelation polymer (TGP)
      can be used as a delivery device to deploy dermal fibroblasts and cytokines into
      experimental aneurysms in rats. METHODS: The right common iliac artery of rats
      was surgically ligated and an experimental aneurysm was created by applying
      exogenous elastase. Seven days later, two aneurysms were harvested and used as
      controls (Group A), two were embolized with pure TGP (Group B), two were
      embolized with TGP and basic fibroblast growth factor (bFGF) (Group C) and two
      were embolized with TGP loaded with rat dermal fibroblasts (Group D). The
      aneurysms were also embolized with TGP mixed with dermal fibroblasts and bFGF at
      different concentrations (10 ng/ml: Group E (n=2), 100 ng/ml: Group F (n=2), 1000
      ng/ml: Group G (n=2)). Each aneurysm sample was harvested after 7 days and
      histologic analyses were performed. RESULTS: The most advanced thrombus
      organization in the aneurysm, such as prominent fibroblast proliferation and
      collagen deposition, was observed in Groups E, F and G, although there was no
      noticeable difference between the groups. Moderate thrombus organization was seen
      in Group D and minimal thrombus organization was seen in Groups B and C.
      CONCLUSIONS: TGP mixed with both dermal fibroblasts and bFGF induced the most
      advanced thrombus organization in the experimental aneurysms followed by TGP
      mixed only with dermal fibroblasts. TGP may be useful as a delivery device to
      deploy fibroblasts and cytokines into aneurysms.

PMID- 23012274
TI  - Genome sequence of the alkaliphilic bacterium Nitritalea halalkaliphila type
      strain LW7, isolated from Lonar Lake, India.
AB  - An alkaliphilic bacterium, Nitritalea halalkaliphila LW7, which belongs to the
      family Cyclobacteriacae in the phylum Bacteroidetes, was isolated from Lonar Lake
      in Maharastra, India. Here we announce the draft genome sequence of the type
      strain LW7, which contains 3,633,701 bp with a G+C content of 48.58%.

PMID- 23012275
TI  - Draft genome sequence of Halomonas smyrnensis AAD6T.
AB  - Halomonas smyrnensis AAD6(T) is a Gram-negative, aerobic, exopolysaccharide
      producing, and moderately halophilic bacterium that produces levan, a fructose
      homopolymer with many potential uses in various industries. We report the draft
      genome sequence of H. smyrnensis AAD6(T), which will accelerate research on the
      rational design and optimization of microbial levan production.

PMID- 23012276
TI  - Complete genome sequence of Helicobacter cinaedi type strain ATCC BAA-847.
AB  - Here we report the completely annotated genome sequence of the Helicobacter
      cinaedi type strain (ATCC BAA-847), which is an emerging pathogen that causes
      cellulitis and bacteremia. The genome sequence will provide new insights into the
      diagnosis, pathogenic mechanisms, and drug resistance of H. cinaedi.

PMID- 23012277
TI  - Genome sequence of the plant pathogen Pseudomonas syringae pv. panici LMG 2367.
AB  - Pseudomonas syringae pv. panici is a phytopathogenic bacterium causing brown
      stripe disease in economically important crops worldwide. Here, we announce the
      draft genome sequence of Pseudomonas syringae pv. panici LMG2367 to provide
      further valuable insights for comparison of the pathovars among species
      Pseudomonas syringae.

PMID- 23012278
TI  - Draft genome sequences of Helicobacter pylori isolates from Malaysia, cultured
      from patients with functional dyspepsia and gastric cancer.
AB  - Helicobacter pylori is the main bacterial causative agent of gastroduodenal
      disorders and a risk factor for gastric adenocarcinoma and mucosa-associated
      lymphoid tissue (MALT) lymphoma. The draft genomes of 10 closely related H.
      pylori isolates from the multiracial Malaysian population will provide an insight
      into the genetic diversity of isolates in Southeast Asia. These isolates were
      cultured from gastric biopsy samples from patients with functional dyspepsia and
      gastric cancer. The availability of this genomic information will provide an
      opportunity for examining the evolution and population structure of H. pylori
      isolates from Southeast Asia, where the East meets the West.

PMID- 23012279
TI  - Genome sequence of Lactobacillus ingluviei, a bacterium associated with weight
      gain in animals.
AB  - We report the draft genome sequence of Lactobacillus ingluviei strain Autruche 4
      (CSURP209) isolated from an ostrich. L. ingluviei is associated with weight gain
      in mice. This genome sequence may help us understand the obesity-induced
      mechanisms of intestinal bacteria.

PMID- 23012280
TI  - Genome sequence of Reyranella massiliensis, a bacterium associated with amoebae.
AB  - Reyranella massiliensis is an Alphaproteobacterium member of the class
      Rhodospirillaceae, growing in amoebae. We sequenced the genome of type strain
      521(T). It is composed of a 5,792,218-bp chromosome and encodes 5,675 protein
      coding genes and 53 RNA genes, including 3 rRNA genes.

PMID- 23012281
TI  - Complete genome sequence of Amycolatopsis mediterranei S699 based on de novo
      assembly via a combinatorial sequencing strategy.
AB  - The genome of Amycolatopsis mediterranei S699 was resequenced and assembled de
      novo. By comparing the sequences of S699 previously released and that of A.
      mediterranei U32, about 10 kb of major indels was found to differ between the two
      S699 genomes, and the differences are likely attributable to their different
      assembly strategies.

PMID- 23012282
TI  - Genome sequences of Pseudomonas luteola XLDN4-9 and Pseudomonas stutzeri XLDN-R,
      two efficient carbazole-degrading strains.
AB  - Pseudomonas luteola XLDN4-9 and Pseudomonas stutzeri XLDN-R are two efficient
      carbazole-degrading pseudomonad strains. Here we present 4.63- and 4.70-Mb
      assemblies of their genomes. Their annotated key genes for carbazole catabolism
      are similar, which may provide further insights into the molecular mechanism of
      carbazole degradation in Pseudomonas.

PMID- 23012283
TI  - Complete genome sequence of Desulfurococcus fermentans, a hyperthermophilic
      cellulolytic crenarchaeon isolated from a freshwater hot spring in Kamchatka,
      Russia.
AB  - Desulfurococcus fermentans is the first known cellulolytic archaeon. This
      hyperthermophilic and strictly anaerobic crenarchaeon produces hydrogen from
      fermentation of various carbohydrates and peptides without inhibition by
      accumulating hydrogen. The complete genome sequence reported here suggested that
      D. fermentans employs membrane-bound hydrogenases and novel glycohydrolases for
      hydrogen production from cellulose.

PMID- 23012284
TI  - Draft genome sequence of Bacillus endophyticus 2102.
AB  - Bacillus endophyticus 2102 is an endospore-forming, plant growth-promoting
      rhizobacterium isolated from a hypersaline pond in South Korea. Here we present
      the draft sequence of B. endophyticus 2102, which is of interest because of its
      potential use in the industrial production of algaecides and bioplastics and for
      the treatment of industrial textile effluents.

PMID- 23012285
TI  - Draft genome sequences of two Campylobacter jejuni clinical isolates, NW and
      D2600.
AB  - The Campylobacter jejuni human clinical isolates NW and D2600 colonized C57BL/6
      interleukin-10-deficient (IL-10(-/-)) mice without inducing a robust inflammatory
      response (J. A. Bell et al., BMC Microbiol. 9:57, 2009). We announce draft genome
      sequences of NW and D2600 to facilitate comparisons with strains that induce
      gastrointestinal inflammation in this mouse model.

PMID- 23012286
TI  - Genome sequence of the methanotrophic poly-beta-hydroxybutyrate producer
      Methylocystis parvus OBBP.
AB  - Methylocystis parvus OBBP is an obligate methylotroph considered the type species
      of the genus Methylocystis. Two pmoCAB particulate methane monooxygenase operons
      and one additional singleton pmoC paralog were identified in the sequence. No
      evidence of genes encoding soluble methane monooxygenase was found. Comparison of
      M. parvus OBBP and Methylocystis sp. strain Rockwell (ATCC 49242) suggests that
      both species should be taxonomically classified in different genera.

PMID- 23012287
TI  - Draft genome sequence of Weissella koreensis KCTC 3621T.
AB  - Weissella koreensis is a Gram-positive, rod-shaped, nonmotile, and facultative
      anaerobic species belonging to the lactic acid bacteria (LAB). The members of
      this species have been repeatedly isolated from kimchi (a traditional Korean
      fermented food) and are known for their beneficial effects on human and animal
      intestinal microflora through producing various clinically important amino acids
      such as gamma-aminobutyric acid and ornithine. Here we report the genome sequence
      of the type strain of W. koreensis (KCTC 3621(T)) to provide taxonomic and
      functional insights into the species.

PMID- 23012288
TI  - Whole-genome sequencing of Borrelia garinii BgVir, isolated from Taiga ticks
      (Ixodes persulcatus).
AB  - Most Lyme borreliosis cases in Russia result from Borrelia garinii NT29 group
      infection. Borrelias of this group circulate exclusively in Ixodes persulcatus
      ticks, which are seldom found beyond Russia and the far east. Here we report the
      whole-genome sequence of Borrelia garinii BgVir isolated from an I. persulcatus
      female.

PMID- 23012289
TI  - Genome sequence of a nicotine-degrading strain of Arthrobacter.
AB  - We announce a 4.63-Mb genome assembly of an isolated bacterium that is the first
      sequenced nicotine-degrading Arthrobacter strain. Nicotine catabolism genes of
      the nicotine-degrading plasmid pAO1 were predicted, but plasmid function genes
      were not found. These results will help to better illustrate the molecular
      mechanism of nicotine degradation by Arthrobacter.

PMID- 23012290
TI  - Genome sequence of Enterococcus sp. strain C1, an azo dye decolorizer.
AB  - Enterococcus sp. strain C1 is a facultative anaerobe which was coisolated with
      Citrobacter sp. strain A1 from a sewage oxidation pond. Strain C1 could degrade
      azo dyes very efficiently via azo reduction and desulfonation in a
      microaerophilic environment. Here the draft genome sequence of Enterococcus sp.
      C1 is reported.

PMID- 23012291
TI  - Whole-genome sequence of Corynebacterium pseudotuberculosis strain Cp162,
      isolated from camel.
AB  - Corynebacterium pseudotuberculosis is a pathogen of great veterinary and economic
      importance, since it affects livestock, mainly sheep and goats, worldwide,
      together with reports of its presence in camels in several Arabic, Asiatic, and
      East and West African countries, as well as Australia. In this article, we report
      the genome sequence of Corynebacterium pseudotuberculosis strain Cp162, collected
      from the external neck abscess of a camel in the United Kingdom.

PMID- 23012292
TI  - Genome sequence of a highly efficient aerobic denitrifying bacterium, Pseudomonas
      stutzeri T13.
AB  - Pseudomonas stutzeri T13 is a highly efficient aerobic denitrifying bacterium.
      Information about the genome of this aerobic denitrifying bacterium has been
      limited until now. We present the draft genome of P. stutzeri T13. The results
      could provide further insight into the aerobic denitrification mechanism in
      strain T13.

PMID- 23012293
TI  - Genome sequence of a cold-adaptable sulfamethoxazole-degrading bacterium,
      Pseudomonas psychrophila HA-4.
AB  - Pseudomonas psychrophila HA-4 is a cold-adaptable, sulfamethoxazole-degrading
      bacterium. The genes related to its cold adaptation mechanism and
      sulfamethoxazole metabolism were unknown. We present the draft genome of strain
      HA-4. It could provide further insight into the sulfamethoxazole-degrading
      mechanism of strain HA-4.

PMID- 23012294
TI  - Draft genome sequence of Klebsiella pneumoniae subsp. pneumoniae DSM 30104T.
AB  - Klebsiella pneumoniae is a Gram-negative, rod-shaped, nonmotile, and
      opportunistic pathogenic species with clinical importance. It is a part of
      natural flora of humans and animals. Here we report the draft genome sequence of
      the type strain of Klebsiella pneumoniae subsp. pneumoniae (DSM 30104(T)) to
      provide taxonomic and functional insights into the species.

PMID- 23012295
TI  - Analysis of the genome of Mycobacterium abscessus strain M94 reveals an uncommon
      cluster of tRNAs.
AB  - Mycobacterium abscessus is a species of rapidly growing nontuberculous
      mycobacteria that is frequently associated with opportunistic infections in
      humans. Here, we report the annotated genome sequence of M. abscessus strain M94,
      which showed an unusual cluster of tRNAs.

PMID- 23012296
TI  - Understanding the biology of triple-negative breast cancer.
AB  - Greater understanding of the biology of triple-negative breast cancer (TNBC) is
      needed to discern the roughly 60% of node-negative patients who are already cured
      with locoregional therapy from the 40% who need adjuvant systemic therapy to be
      cured. Recent evidence suggests that patients with TNBC whose tumours have an
      activated immune response gene signature have a more favourable outcome than TNBC
      patients without this signature. For the group who needs additional systemic
      therapy, the challenge remains to choose the right systemic drug combination for
      the right TNBC sub-type. Significant heterogeneity exists within the TNBC class
      that is exemplified by differing chemotherapeutic sensitivity observed for some
      sub-types. This heterogeneity establishes the need for identifying
      differentiating molecular markers within the overall class of TNBC disease, which
      may help refine therapeutic management. In this review, we discuss some of these
      promising predictive molecular markers for tailoring therapy. In addition,
      several gene expression profiling and functional studies employing genetic
      screens that help to establish TNBC sub-groups with varying sensitivities to a
      variety of targeted therapies currently under clinical investigation are
      conferred. It is anticipated that a greater understanding of the biology of TNBC
      and its complex heterogeneity will reveal novel targets or identify markers
      around which clinical trials in molecularly well-defined sub-groups can be
      designed.

PMID- 23012297
TI  - Pathological and molecular diagnosis of triple-negative breast cancer: a clinical
      perspective.
AB  - Triple-negative breast cancer (TNBC) is a heterogeneous disease diagnosed by
      immunohistochemistry and is characterised by tumours that do not express estrogen
      receptor (ER) or progesterone receptor (PR) at all, and do not overexpress human
      epidermal growth factor receptor 2 (HER2). Prototypical TNBC is aggressive in
      nature and associated with a poor prognosis, making the accurate diagnosis of the
      disease vitally important for ensuring optimal therapy for patients.
      Morphological and biological analyses can identify subtypes of TNBC, which can
      have different prognoses, and (in the case of the latter) may eventually be used
      to predict response to treatment. This mini-review focuses on clinically relevant
      issues in the diagnosis of TNBC, including the importance of adherence to
      international guidelines for the detection of ER/PR/HER2 status, and the
      relationship between TNBC and the overlapping (yet distinct) intrinsic subtype of
      'basal-like' breast cancer. In addition, we review the potential use of emerging
      biomarkers as surrogates for molecular subtypes and as a means of identifying
      potential responders to new therapies.

PMID- 23012298
TI  - Imaging of triple-negative breast cancer.
AB  - Although triple-negative breast cancer (TNBC) has been studied extensively in the
      oncology and pathology literature, there are few reports on imaging features.
      Emerging data suggest that imaging features of TNBC are substantially different
      from other primary breast cancer immunotypes. In this work, we reviewed multi
      modality imaging features of primary TNBC with emphasis on the appropriate niche
      for each technology in diagnosis, staging and management. TNBC lacks the typical
      suspicious mammographic features of breast cancer; namely irregular mass shape,
      spiculated margins and associated suspicious calcifications. Therefore,
      mammography alone is usually a sub-optimal tool for its initial diagnostic
      evaluation. Ultrasound has a much higher sensitivity, although its diagnostic
      capability may be impaired by associated benign features encountered in 21%-41%
      of TNBC lesions. Magnetic resonance imaging (MRI) consistently demonstrates the
      presence of all TNBC with a higher level of accuracy compared with other tumour
      sub-types, and provides a reliable baseline for neoadjuvant chemotherapy (NAC)
      follow-up. Preliminary studies also suggest that MRI may predict complete NAC
      response in TNBC more sensitively than other methods. [(18)F]2-fluoro-2-deoxy-D
      glucose positron emission tomography ((18)F-FDG-PET) has a higher sensitivity for
      TNBC than estrogen-positive and human epidermal growth factor receptor 2-positive
      tumours, and axillary lymph node metastases are detected with more accuracy
      compared with other tumour molecular sub-types, although low FDG uptake of breast
      cancers in general may limit the routine clinical use of (18)F-FDG-PET in the
      initial diagnosis of TNBC patients and NAC follow-up.

PMID- 23012299
TI  - Locoregional treatments for triple-negative breast cancer.
AB  - The absence of drug-targetable receptors in triple-negative breast cancer (TNBC)
      makes the use of targeted systemic therapy inappropriate for this breast cancer
      subgroup. Although patients with TNBC show sensitivity to some chemotherapy
      regimens, in early-stage disease greater emphasis is placed on locoregional
      treatments, based on surgery and radiation therapy (RT). Ongoing improvements in
      both screening and surgical techniques have reduced the need for radical surgical
      intervention in all breast cancers, and breast-conserving surgery (BCS) followed
      by RT is now increasingly common for all tumour types. However, while evidence
      has clearly established the importance of post-surgical RT for favourable long
      term outcomes in breast cancer, it is less well-established as to where and under
      which conditions more radical surgeries than BCS, such as modified radical
      mastectomy (MRM), may be indicated for TNBC. A high proportion of TNBC tumours
      are BRCA1-mutated and therefore patients with this type of tumour are at a
      potentially elevated risk of ipsilateral or contralateral recurrence. In
      addition, while some studies indicate that post-BCS locoregional TNBC relapse
      rates generally appear similar to other tumour types, some evidence suggests that
      distant relapse rates may be higher. There is evidence that some subtypes of TNBC
      may require MRM rather than BCS for optimal long-term outcomes. More research is
      needed to establish whether TNBC-specific approaches to locoregional treatment
      may be required.

PMID- 23012300
TI  - Neoadjuvant treatments for triple-negative breast cancer (TNBC).
AB  - Neoadjuvant chemotherapy provides a means both of improving subsequent surgical
      intervention and of testing novel therapies or combinations. Historically, triple
      negative breast cancer (TNBC) has responded well in the neoadjuvant setting, with
      rates of pathological complete response (pCR) commonly higher than for other
      breast tumour types. However, more than half of TNBC patients do not achieve a
      pCR and have a very poor prognosis. The lack of drug-targetable receptors on TNBC
      tumours has made improving the available interventions in TNBC an area of
      important medical need. The routine use of neoadjuvant anthracycline/taxane
      combinations in TNBC is currently being supplemented by ongoing investigations of
      their use with other types of agent. In particular, the substantial proportion of
      TNBC tumours associated with BRCA1 mutations is driving clinical research into
      the use of DNA-damaging agents such as platinums, as well as of potentiators of
      DNA damage such as the investigational agent iniparib and inhibitors of poly-ADP
      ribose polymerase such as olaparib. Tyrosine kinase receptor inhibitors and
      microtubule-targeting inhibitors of cell cycling are also under active
      investigation. The use of neoadjuvant treatment with pCR as a surrogate of
      overall survival will allow the rapid evaluation and comparison of these and
      other much-needed new treatments for TNBC.

PMID- 23012301
TI  - Adjuvant treatments for triple-negative breast cancers.
AB  - Conventional chemotherapy is the mainstay of adjuvant systemic treatment for most
      patients with early triple-negative breast cancer (TNBC). At present, comparisons
      between adjuvant chemotherapy regimens are retrospective in nature, and so the
      optimal drugs or drug combinations have not been established for patients with
      early TNBC. In retrospective subgroup analyses, taxanes are more effective than 5
      fluorouracil in combination with cyclophosphamide and doxorubicin. Classical CMF
      (cyclophosphamide, methotrexate and 5-fluorouracil) has shown efficacy, whereas
      few data on the role of anthracyclines are available. An unplanned subgroup
      analysis of one randomised study suggests that capecitabine adds efficacy to a
      taxane-anthracycline regimen, but this observation requires confirmation. High
      dose adjuvant chemotherapy is considered experimental. Ongoing trials are
      comparing standard adjuvant regimens with regimens that integrate an anti
      angiogenic agent, a platin or maintenance capecitabine. Inhibitors of DNA repair
      or specific tyrosine kinases have not yet been addressed in the adjuvant setting.
      In the absence of data from prospective trials that focus on adjuvant therapy of
      early TNBC, several regimens, such as a taxane and an anthracycline-containing
      regimen or classical CMF may be considered reasonable choices.

PMID- 23012302
TI  - Optimal strategies for the treatment of metastatic triple-negative breast cancer
      with currently approved agents.
AB  - Triple-negative breast cancer (TNBC) is an aggressive histological subtype with
      limited treatment options and very poor prognosis following progression after
      standard chemotherapeutic regimens. Resistance to current standard therapies such
      as anthracyclines or taxanes limits the available options for previously treated
      patients with metastatic TNBC to a small number of non-cross-resistant regimens,
      and there is currently no preferred standard chemotherapy. Duration of response
      is usually short, with rapid relapse very common and median survival of just 13
      months. The newly approved agent eribulin has shown a survival benefit in
      patients who had previously been treated with anthracycline- or taxane-containing
      regimens, including in patients with TNBC. Platinum-based regimens are an
      emerging option for patients with BRCA1 mutation, and newer targeted agents such
      as anti-angiogenic treatment with bevacizumab or anti-epidermal growth factor
      receptor treatment with cetuximab, have shown some benefit in combination
      therapy. However, there remains an urgent unmet need for improved targeted agents
      for this patient population. Improved treatment may be facilitated by biomarker
      led understanding of subgroup molecular targets, which may predict benefit from
      currently approved agents, as well as newer targeted drugs.

PMID- 23012303
TI  - Triple-negative breast cancer in focus: from biology to novel therapeutics.
      Editorial.

PMID- 23012304
TI  - Triple-negative breast cancer in the older population.
AB  - Breast cancer in advanced age has been associated with a slightly increased
      probability of favourable tumour biology (e.g. hormone receptor-positive and
      human epidermal growth factor-2 [HER2]-negative by immunohistochemistry).
      Nevertheless, a substantial proportion of older women (~ 15-18%) still develop
      'triple-negative' breast cancer (TNBC), which is generally associated with a poor
      prognosis. To date, there have been very few investigations comparing the
      prognosis of younger and older women with TNBC; however, some emerging studies
      suggest that older patients with TNBC may have a better outcome when compared
      with their younger counterparts. The reasons for these differences in prognosis
      have yet to be fully elucidated, but may be due to age-related biological
      variations, as suggested by observed differences in the distribution of
      histological subtypes of TNBC, or perhaps other unknown (biological) factors.
      Despite the evidence of benefit of chemotherapy in TNBC in older women, there is
      still a tendency for geriatric patients to receive less adjuvant chemotherapy
      than their younger counterparts.

PMID- 23012305
TI  - Emerging targeted therapies in triple-negative breast cancer.
AB  - Standard chemotherapy regimens can prove effective for patients with early triple
      negative breast cancer (TNBC); however, patients with advanced disease typically
      respond poorly and rapidly progress, and the outcome is poor. New targeted
      therapies are therefore an urgent unmet medical need for this patient population.
      Translational and clinical studies into new TNBC treatments have been facilitated
      by the increased understanding of the aberrant signal transduction pathways
      regulating growth and survival and the development of chemoresistance in TNBC.
      Some of the established targeted agents that have been approved in other
      indications may prove beneficial to patients with TNBC; however, in the absence
      of approved targeted agents for the treatment of TNBC, most new agents remain
      experimental. Increased understanding of molecular profiles of TNBC subtypes is
      likely to improve therapeutic strategies with targeted agents. Novel strategies
      have reached clinical evaluation in patients with TNBC, including targeting
      angiogenesis vascular endothelial growth factor and proliferation signalling
      (receptor tyrosine kinases and mammalian target of rapamycin). Aggressive TNBCs
      have been found to associate closely with BRCA1 mutation or dysregulation. The
      recent development of new investigational agents targeting DNA repair, either
      directly with poly(adenosine disphosphate-ribose) polymerase inhibitors or
      indirectly through DNA-binding or DNA-damage potentiation, is a major focus of
      current clinical studies. These and other targeted therapies represent a new
      approach to TNBC therapy.

PMID- 23012306
TI  - Triple-negative breast cancer: epidemiological considerations and
      recommendations.
AB  - Breast cancer is a major problem for global public health. Breast Cancer is the
      most common incident form of cancer in women around the world. The incidence is
      increasing while mortality is declining in many high-income countries. The last
      decade has seen a revolution in the understanding of breast cancer, with new
      classifications proposed that have significant prognostic value and provide
      guides to treatment options. Breast cancers that demonstrate the absence of
      oestrogen receptor and progesterone receptor and no overexpression of human
      epidermal growth factor receptor 2 (HER2) are referred to as triple-negative
      breast cancer (TNBC). There is now evidence emerging from epidemiological studies
      regarding important characteristics of this group of tumours that carry a
      relatively poorer prognosis than the major breast cancer sub-types. From this
      review of available data and information, there are some consistent findings that
      emerge. Women with TNBC experience the peak risk of recurrence within 3 years of
      diagnosis, and the mortality rates appear to be increased for 5 years after
      diagnosis. TNBC represents 10%-20% of invasive breast cancers and has been
      associated with African-American race, deprivation status, younger age at
      diagnosis, more advanced disease stage, higher grade, high mitotic indices,
      family history of breast cancer and BRCA1 mutations. TNBC is regularly reported
      to be three times more common in women of African descent and in pre-menopausal
      women, and carries a poorer prognosis than other forms of breast cancer. Although
      prospects for prevention of non-hormone-dependent breast cancer are currently
      poor, it is still important to understand the aetiology of such tumours. There
      remains a great deal of work to be done to arrive at a comprehensive picture of
      the aetiology of breast cancer. Key recommendations are that there is a clear and
      urgent need to have more epidemiological studies of the breast cancer sub-types
      to integrate aetiological and lifestyle factors for prevention of incidence and
      death, and to have more population-based information of the clinical and
      biological relevance from cancer registries.

PMID- 23012307
TI  - Cardiac testing and outcomes in infants after an apparent life-threatening event.
AB  - OBJECTIVES: We sought to determine the yield of cardiac testing and to identify
      predictors of cardiac disease in infants with an apparent life-threatening event
      (ALTE). DESIGN: Retrospective longitudinal cohort study. SETTING: Paediatric
      hospital providing primary and tertiary care that is part of an integrated
      healthcare system. PATIENTS: Infants hospitalised for an ALTE from 1999 to 2003.
      MAIN EXPOSURES: Cardiac testing used at time of ALTE and results, and clinical
      risk factors for cardiac disease. OUTCOME MEASURES: Short-term (during
      hospitalisation) and long-term (through November 2009) follow-up for any
      diagnosis of significant cardiac anatomic or rhythm abnormality. RESULTS: Study
      criteria were met by 485 infants (mean age 1.9, SD+/-2.2 months; 49% boys).
      Cardiac testing was performed on 219 (45%) patients during ALTE hospitalisation,
      identifying two patients with significant cardiac disease (cardiomyopathy,
      ventricular pre-excitation). During 7.7 years of follow-up, three additional
      significant cardiac diagnoses (ventricular pre-excitation, frequent ventricular
      ectopy, moderate aortic stenosis) were identified. All cardiac tests had low
      positive predictive value (PPV). Significant cardiac disease was associated with
      prematurity (22% vs 80%, p=0.002), but not age, gender, prior ALTE or rescue
      breaths. CONCLUSIONS: This longitudinal study of an ALTE cohort revealed
      significant cardiac disease in <1% of patients. Prematurity was the only clinical
      predictor identified. ECG was sensitive for identifying significant cardiac
      disease, but routine testing warrants further investigation because of the low
      PPV.

PMID- 23012308
TI  - Cost of epimacular brachytherapy for treatment-naive neovascular age-related
      macular degeneration.

PMID- 23012309
TI  - Declining incidence of eyelid cancers in Singapore over 13 years: population
      based data from 1996 to 2008.
AB  - PURPOSE: To describe the epidemiology and trends in eyelid malignancies in
      Singapore from 1996 to 2008. METHODS: The Singapore Cancer Registry has been
      collecting epidemiological data of all cancers seen in Singapore since 1968. Data
      of all eyelid cancers from 1996 to 2008 were retrieved for analysis. The age
      standardised incidence rates and age-specific incidence rates were calculated
      with the direct method, using the 2000 world population as a standard. RESULTS:
      There were a total of 160 male patients (48%) and 173 female patients (52%). The
      median age at diagnosis was 66 years (range 31-95) for male subjects and 67 years
      (35-99) for female subjects. The average annual age-standardised incidence rate
      of all eyelid cancers over the 13 years was 5.0 per million. A significant
      decrease in rates from 6.6 per million in the 1996-1998 period to 3.9 per million
      in the 2005-2008 period with an annual percentage change of 3.6% (95% CI -6.5 to
      0.7%; p=0.02) was noted for women. The most common cancer was basal cell
      carcinoma (82%), followed by sebaceous gland carcinoma (11%) and squamous cell
      carcinoma (4%). CONCLUSIONS: The annual age-standardised incidence rates for male
      and female residents showed a steady decline over the last 13 years. These data
      suggest that factors related to sun protection have resulted in reduced eyelid
      cancers over time and provide a basis for such public health programmes
      elsewhere.

PMID- 23012310
TI  - Health-related quality of life of Gaza Palestinians in the aftermath of the
      winter 2008-09 Israeli attack on the Strip.
AB  - BACKGROUND: We document the health-related quality of life (HRQoL) of people
      living in the Gaza Strip 6 months after 27 December 2008 to 18 January 2009,
      Israeli attack. METHODS: Cross-sectional survey 6 months after the Israeli
      attack. Households were selected by cluster sampling in two stages: a random
      sample of enumeration areas (EAs) and a random sample of households within each
      chosen EA. One randomly chosen adult from each of 3017 households included in the
      survey completed the World Health Organization Quality of Life instrument, in
      addition to reported information on distress, insecurities and threats. RESULTS:
      Mean HRQoL score (range 0-100) for the physical domain was 69.7, followed by the
      psychological (59.8) and the environmental domain score (48.4). Predictors of
      lower (worse) scores for all three domains were: lower educational levels,
      residence in rural areas, destruction to one's private property or high levels of
      distress and suffering. Worse physical and psychological domain scores were
      reported by people who were older and those living in North Gaza governorate.
      Worse physical and environmental domain scores were reported by people with no
      one working at home, and those with worse standard of living levels. Respondents
      who reported suffering stated that the main causes were the ongoing siege, the
      latest war on the Strip and internal Palestinian factional violence. CONCLUSION:
      Results reveal poor HRQoL of adult Gazans compared with the results of WHO multi
      country field trials and significant associations between low HRQoL and war
      related factors, especially reports of distress, insecurity and suffering.

PMID- 23012311
TI  - Improving shop floor compliance with age restrictions for alcohol sales:
      effectiveness of a feedback letter intervention.
AB  - PURPOSE: In this study, we investigated the effects and handling of an
      intervention to increase compliance with age limits regarding alcohol sales. The
      intervention tested in this field experiment was a feedback letter sent to
      alcohol outlets about their individual compliance results based on a mystery
      shopping study. METHOD: We measured compliance in 146 alcohol outlets
      (cafeterias, supermarkets, bars, liquor stores and youth centres) in one region
      in the Netherlands with 15-year-old mystery shoppers. About half (n=72) of the
      outlets received the intervention letter (the experimental group). After this
      intervention, we measured compliance again (n=138). Then we sent the same letter
      to the control group and interviewed all the outlets regarding their handling of
      the intervention (n=106). RESULTS: After the experimental group received the
      letter, compliance increased significantly (from 18.1% to 32.4%). In the control
      group, compliance did not change. Of the outlets interviewed, 81% stated that
      they had received the letter, and the action most commonly taken was to bring the
      letter to the attention of their staff. CONCLUSIONS: Positive feedback letters
      are more often copied and shared integrally with personnel, compared with
      negative letters. Compliance with respect to underage alcohol sales can be
      improved, although compliance levels remain low in the Netherlands.

PMID- 23012313
TI  - A phytooxysterol, 28-homobrassinolide modulates rat testicular steroidogenesis in
      normal and diabetic rats.
AB  - Steroidogenesis in testicular cells depends upon the availability of cholesterol
      within testicular mitochondria besides the activities of 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD, 17beta-hydroxysteroid dehydrogenase [17b-HSD]), and the
      tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding
      protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is
      regulated by endogenous oxycholesterols acting through nuclear hormone receptors.
      Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through
      diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its
      role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore
      assessed using normal and streptozotocin-induced diabetic male rats.
      Administration of 28-HB (333 ug/kg body weight) by oral gavage for 15 consecutive
      days to experimental rats diminished LPO, increased antioxidant enzyme, 3beta-HSD
      and 17beta-HSD activities, and elevated StAR and ABP expression and T level in
      rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic
      rat testis.

PMID- 23012314
TI  - Nitric oxide and carbon monoxide production and metabolism in preeclampsia.
AB  - OBJECTIVE: To elucidate the regulation of the nitric oxide (NO) and carbon
      monoxide (CO) pathways in preeclampsia and to evaluate the ratio of asymmetric
      dimethylarginine (ADMA) to symmetric dimethylarginine (SDMA) as a marker for
      preeclampsia. METHODS: Maternal plasma and placental samples were obtained from
      20 participants with preeclampsia and 23 controls. Enzyme-linked immunosorbent
      assay was used to measure plasma NO, ADMA, and SDMA as well as placental NO and
      hemeoxygnase 1 (HO-1). Western blot was used to measure placental
      dimethylarginine dimethylaminotransferases (DDAH-I and DDAH-II). RESULTS:
      Placental DDAH-I, placental DDAH-II, placental NO, and placental HO-1 were
      significantly decreased in participants with preeclampsia. While ADMA and SDMA
      levels were decreased in preeclampsia, the ADMA-SDMA ratio was not significantly
      different. CONCLUSIONS: Decreased DDAH and HO with preeclampsia suggest that they
      are important points in the regulatory pathways of NO and CO production that are
      altered in preeclampsia. The ADMA-SDMA ratio is not a useful test for
      preeclampsia.

PMID- 23012315
TI  - Vitamin D elicits anti-inflammatory response, inhibits contractile-associated
      proteins, and modulates Toll-like receptors in human myometrial cells.
AB  - Infection during pregnancy triggers inflammation, which can increase myometrial
      contractions and the risk of premature labor and delivery. In this study, we
      assessed the effects of vitamin D, an anti-inflammatory ligand on cytokines,
      chemokines, toll-like receptors, and contractile-associated proteins on
      immortalized human myometrial smooth muscle (UtSM) cells stimulated with
      lipopolysaccharide (LPS), a bacterial endotoxin, or interleukin (IL)-1beta and
      measured Toll-like receptor (TLR)-10 expression in pregnant myometrial tissues. A
      superarray analysis revealed downregulation of the chemokines monocyte
      chemoattractant protein (MCP)-1, Chemokine (C-X-C motif) ligand (CXCL)-10, CXCL
      11, and chemokine (C-X3-C motif) ligand (CX3CL)-1; the proinflammatory cytokines
      IL-13 and tumor necrosis factor (TNF)-alpha; the TLR-4 and -5 and triggering
      receptor expressed on myeloid cells (TREM)-2 and upregulation of the anti
      inflammatory cytokine IL-10, as well as Toll interacting protein (TOLLIP) and
      TREM-1 in vitamin D-treated UtSM cells. In the presence of LPS, vitamin D caused
      dose-dependent decreases in the messenger RNA expression of MCP-1, IL-1beta, IL
      13, TNF-alpha, TLR-4, and TLR-5, the contractile-associated proteins connexin 43,
      the oxytocin receptor, and the prostaglandin receptor but caused increases in IL
      10 and TLR-10 in UtSM cells. The TLR-10 expression was higher in human myometrial
      tissue obtained from women at term not in labor compared to labor. Vitamin D also
      attenuated IL-1beta-induced MCP-1, IL-6, connexin 43, cyclooxygenase (COX)-2, and
      prostaglandin receptor expression. Western analysis showed that vitamin D
      decreased MCP-1, TLR-4, and connexin 43 in the presence of LPS and decreased
      connexin 43 in the presence of IL-1beta. Our results suggest that vitamin D can
      potentially decrease infection-induced increases in cytokines and contractile
      associated proteins in the myometrium.

PMID- 23012316
TI  - Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent
      pathways intrinsic to the ovary.
AB  - Ulipristal acetate (UPA), a progesterone receptor (PR) modulator, is used as an
      emergency contraceptive in women. Here, using a mouse model, we investigated the
      mechanism of action of UPA as an ovulation blocker. In mice, ovulation is induced
      ~12 hours following the treatment with exogenous gonadotropins, including human
      chorionic gonadotropin (hCG), which mimics the action of luteinizing hormone
      (LH). When administered within 6 hours of hCG treatment, UPA is a potent blocker
      of ovulation. However, UPA's effectiveness declined significantly when it was
      given at 8 hours post hCG. Our study revealed that, when administered within 6
      hours of hCG, UPA blocks ovulation by inhibiting PR-dependent pathways intrinsic
      to the ovary. At 8 hours post hCG, when the PR signaling has already occurred,
      UPA is unable to block ovulation efficiently. Collectively, these results
      indicated that UPA, when administered within a critical time window following the
      LH surge, blocks PR-dependent pathways in the ovary to function as an effective
      antiovulatory contraceptive.

PMID- 23012318
TI  - The extrapituitary effects of GnRH antagonists and their potential clinical
      implications: a narrated review.
AB  - Potential roles of gonadotropin-releasing hormone (GnRH) antagonists on GnRH/GnRH
      receptor systems and their effects on the extrapituitary tissues are largely
      elusive. In this narrated review, we summarized the systemic effects of GnRH
      antagonists on ovary, endometrium, embryo implantation, placental development,
      fetal teratogenicity, reproductive tissue cancer cells, and heart while briefly
      reviewing the GnRH and GnRH receptor system. GnRH antagonists may have direct
      effects on ovarian granulosa cells. Data are conflicting regarding their effects
      on endometrial receptivity. The GnRH antagonists may potentially have detrimental
      effect on early placentation by decreasing the invasive ability of
      cytotrophoblasts if the exposure to them occurs during early pregnancy. The GnRH
      antagonists were not found to increase the rates of congenital malformations.
      Comparative clinical data are required to explore their systemic effects on
      various extrapituitary tissues such as on cardiac function in the long term as
      well as their potential use in other human cancers that express GnRH receptors.

PMID- 23012317
TI  - Mechanical stretch increases brain natriuretic peptide production and secretion
      in the human fetal membranes.
AB  - Brain natriuretic peptide (BNP) is synthesized by human fetal membranes, both the
      amnion and chorion. This locally produced BNP inhibits the contraction of the
      human myometrium, contributing to the maintenance of myometrial quiescence during
      pregnancy. We tested the hypothesis that BNP production is increased by fetal
      membrane stretching, which is predicted to occur in the expanding uterus, and
      inhibited by epidermal growth factor (EGF), whose production in the fetal
      membranes increases in late pregnancy. Term fetal membranes were obtained during
      elective cesarean delivery before labor. Sections of membranes were placed in an
      isolated chamber containing DMEM: F12 medium (37 degrees C) and stretched with a
      35 g weight. Medium and tissue samples were collected at 0, 3, 6, 18, and 24
      hours for measurement of messenger RNA (mRNA) and BNP levels in the
      presence/absence of EGF (2 * 10(-9 )mol/L). Inducible nitric oxide synthase
      (iNOS) and beta-actin were also evaluated to discard a nonspecific effect of
      mechanical stretch on protein expression. We found that amnion and chorion
      stretching increased the BNP mRNA (reverse transcription-polymerase chain
      reaction [RT-PCR]) and protein (radioimmunosorbent assay [RIA]) levels from 18
      hours onward. The effect of stretching was inhibited by EGF (2 * 10(-9) mol/L).
      Stretch did not increase iNOS or beta-actin protein levels. We concluded that
      chorion and amnion stretching may increase BNP expression in the fetal membranes
      during pregnancy, while increasing biological activity of EGF may decrease BNP
      production in the chorion and amnion late in pregnancy. We postulate BNP is an
      important regulator of myometrial contractility during pregnancy, and its
      production is modulated by both stretch and progressive increase in EGF levels
      during pregnancy.

PMID- 23012319
TI  - Alterations of microRNA expression patterns in human cervical carcinoma cells (Ca
      Ski) toward 1'S-1'-acetoxychavicol acetate and cisplatin.
AB  - The aims of this study were to investigate the combined effects of a natural
      compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV
      positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity
      and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs)
      modulated in response toward ACA and/or CDDP. It was revealed that both ACA and
      CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone
      agent, while synergistic effects were observed when used in combination with a
      combination index (CI) value of 0.74 +/- 0.01 and 0.85 +/- 0.01 in Ca Ski and
      HeLa cells, respectively. A total of 25 miRNAs were found to be significantly
      differentially expressed in response to ACA and/or CDDP. These include hsa-miR
      138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in
      signaling pathways regulating apoptosis and cell cycle progression. In
      conclusion, ACA acts as a chemosensitizer which synergistically potentiates the
      cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression
      upon administration of ACA and/or CDDP suggests that miRNAs play an important
      role in anticancer drug responses, which can be manipulated for therapeutic
      purposes.

PMID- 23012320
TI  - Responsiveness of the VISA-P scale for patellar tendinopathy in athletes.
AB  - BACKGROUND: Patient-reported outcome measures are increasingly used in sports
      medicine to assess results after treatment, but interpretability of change for
      many instruments remains unclear. OBJECTIVE: To define the minimum clinically
      important difference (MCID) for the Victorian Institute of Sport Assessment scale
      (VISA-P) in athletes with patellar tendinopathy (PT) who underwent conservative
      treatment. METHODS: Ninety-eight athletes with PT were enrolled in the study.
      Each participant completed the VISA-P at admission, after 1 week, and at the
      final visit. Athletes also assessed their clinical change at discharge on a 15
      point Likert scale. We equated important change with a score of >=3 (somewhat
      better). Receiver-operating characteristic (ROC) curve analysis and mean change
      score were used to determine MCID. Minimal detectable change was calculated. The
      effect of baseline scores on MCID and different criteria used to define important
      change were investigated. A Bayesian analysis was used to establish the posterior
      probability of reporting clinical changes related to MCID value. RESULTS:
      Athletes with PT who showed an absolute change greater than 13 points in the VISA
      P score or 15.4-27% of relative change achieved a minimal important change in
      their clinical status. This value depended on baseline scores. The probability of
      a clinical change in a patient was 98% when this threshold was achieved and 45%
      when MCID was not achieved. CONCLUSIONS: Definition of the MCID will enhance the
      interpretability of changes in the VISA-P score in the athletes with PT, but
      caution is required when these values are used.

PMID- 23012321
TI  - Regulation of ion channels by the serum- and glucocorticoid-inducible kinase
      SGK1.
AB  - The ubiquitously expressed serum- and glucocorticoid-inducible kinase-1 (SGK1) is
      genomically regulated by cell stress (including cell shrinkage) and several
      hormones (including gluco- and mineralocorticoids). SGK1 is activated by insulin
      and growth factors through PI3K and 3-phosphoinositide-dependent kinase PDK1.
      SGK1 activates a wide variety of ion channels (e.g., ENaC, SCN5A, TRPV4-6, ROMK,
      Kv1.3, Kv1.5, Kv4.3, KCNE1/KCNQ1, KCNQ4, ASIC1, GluR6, ClCKa/barttin, ClC2, CFTR,
      and Orai/STIM), which participate in the regulation of transport, hormone
      release, neuroexcitability, inflammation, cell proliferation, and apoptosis. SGK1
      sensitive ion channels participate in the regulation of renal Na(+) retention and
      K(+) elimination, blood pressure, gastric acid secretion, cardiac action
      potential, hemostasis, and neuroexcitability. A common (~3-5% prevalence in
      Caucasians and ~10% in Africans) SGK1 gene variant is associated with increased
      blood pressure and body weight as well as increased prevalence of type II
      diabetes and stroke. SGK1 further contributes to the pathophysiology of allergy,
      peptic ulcer, fibrosing disease, ischemia, tumor growth, and neurodegeneration.
      The effect of SGK1 on channel activity is modest, and the channels do not require
      SGK1 for basic function. SGK1-dependent ion channel regulation may thus become
      pathophysiologically relevant primarily after excessive (pathological)
      expression. Therefore, SGK1 may be considered an attractive therapeutic target
      despite its broad range of functions.

PMID- 23012322
TI  - C1orf61 acts as a tumor activator in human hepatocellular carcinoma and is
      associated with tumorigenesis and metastasis.
AB  - The genomic amplification of chromosome 1q long arm, the chromosomal region
      containing C1orf61, is a common event in human cancers. However, the expression
      pattern of chromosome 1 open reading frame 61 (C1orf61) in hepatocellular
      carcinoma (HCC) and its effects on HCC progression remain unclear. We have
      previously reported that C1orf61 is highly up-regulated during human
      embryogenesis. In this study, we report that C1orf61 expression is associated
      with the progression of liver disease. We found that C1orf61 is up-regulated in
      hepatic cirrhosis tissues and is further up-regulated in primary HCC tumors.
      Moreover, hepatitis B virus (HBV)-positive patients exhibited significantly
      higher levels of C1orf61 expression than HBV-negative patients. The evaluation of
      highly malignant HCC cell lines revealed high protein expression levels of
      C1orf61. Furthermore, the C1orf61 protein was found to be predominantly
      distributed within the cytoplasm. The ectopic expression of C1orf61 in the
      nonmalignant L02 cell line promoted cellular proliferation and colony formation
      in vitro, as well as cell cycle progression via the regulation of the expression
      of specific cell cycle-related proteins. In addition, the overexpression of
      C1orf61 in L02 cells facilitated cellular invasion and metastasis. The down
      regulation of epithelial markers (E-cadherin and occludin) and the up-regulation
      of mesenchymal markers (N-cadherin, vimentin, and snail) suggested that the
      overexpression of C1orf61 induced the epithelial-mesenchymal transition (EMT)
      that is linked to metastasis. Taken together, our findings demonstrate, for the
      first time, the roles of C1orf61 in HCC tumorigenesis and metastasis.

PMID- 23012323
TI  - Piloting HIV rapid testing in community-based settings in Estonia.
AB  - BACKGROUND: In the European Union it is estimated that up to 30% of HIV-infected
      people are not aware of their status. Community-based testing (CBT) models are
      implemented to increase the uptake of HIV testing. AIMS: The aim of this project
      was to assess the feasibility and acceptance of HIV rapid testing in CBT settings
      in Estonia to identify non-clinical recruitment venues for people more likely to
      engage in high-risk behaviours. METHODS: Participants for this anonymous, cross
      sectional study were recruited from a syringe exchange programme and gay-oriented
      locations using convenience sampling. Socio-demographic and HIV testing
      preferences data were collected using a semi-structured questionnaire. HIV rapid
      testing was performed using Determine HIV-1/2 (Abbott) rapid test system.
      RESULTS: With a participation rate of 88.3%, this project enrolled 308 persons
      and identified 58 preliminary positive cases. Out of them, 52 reported injecting
      drug use in last 12 months and 30 reported no previous HIV test. Approximately
      45% of all participants preferred rapid testing while 25% reported a preference
      for a full blood test. CONCLUSIONS: This project demonstrates that HIV rapid
      testing in community-based settings in Eastern Europe can be an effective
      approach for reaching people who engage in high-risk behaviours and increasing
      the number of HIV-infected people who are aware of their status.

PMID- 23012324
TI  - Social and diagnostic inequality in health.
AB  - Empirical studies of social inequalities in health commonly take the diagnosing
      of disease for granted. Social inequalities in health are seen as the result of
      social processes, yet the diagnosis itself is rarely considered to contribute to
      such inequality. We argue that the influence of sociocultural and cognitive bias
      in the diagnosing process follows a social pattern, such that certain diagnoses
      are disproportionally over- or underrepresented in different socioeconomic groups
      due to interpretive bias of underlying symptoms. METHODS: Norwegian data on sick
      leave for diffuse musculoskeletal and diffuse psychiatric disease in 2006 were
      analysed to study the distribution of the two diagnoses in different status
      groups. Socioeconomic status was measured by years of education. Diagnoses and
      occupational codes were based on national registers; diagnoses in accordance with
      the International Classification of Primary Care second edition. We compared
      occupations in technical sectors to occupations in the health sector and the
      relative number of cases of sick leave controlled for years of education, gender,
      occupational sector, and diagnosis. Data were analysed by cross-tabulation, ratio
      of diffuse psychiatric/musculoskeletal diseases, and logistic regression.
      RESULTS: The ratio of diffuse psychiatric/musculoskeletal diseases increases with
      education and decreases if the employee works in a technical job. CONCLUSION: The
      results challenge the traditional explanation that job features alone can explain
      the distribution of disease and suggest that a part of the persistent social
      inequality in health can be caused by the diagnosing process. In order to reach a
      better understanding of the processes behind the social inequalities in health,
      the diagnosing process itself should also be studied.

PMID- 23012325
TI  - Socioeconomic inequalities in dental services utilisation in a Norwegian county:
      the third Nord-Trondelag Health Survey.
AB  - AIM: To assess the level of socioeconomic inequity in dental care utilisation in
      Norway and enable comparison with recent international comparative studies.
      METHODS: We studied dental care utilisation among 17,136 men and 21,414 women in
      the third Nord-Trondelag Health Survey (2006-08). Respondents aged 20 years and
      above were included in the study, and analyses were also performed within
      subgroups of age and gender (20-39, 40-59, and >=60 years). Income-related
      horizontal inequity was estimated by means of concentration indices. Education
      related inequity was estimated as relative risks. RESULTS: We found consistent
      pro-rich income inequity among men and women of all ages. The level of income
      inequity was highest among men and women >=60 years, and in this group the income
      gradient was steepest between the poorest and the middle quintiles. Pro-educated
      inequity was found exclusively among men and women >=60 years. General attendance
      was high (77%). CONCLUSION: The overall level of income-related inequity in
      dental services utilisation was low compared to other European countries as
      reported in two recent international studies of socioeconomic inequalities in
      dental care utilisation. Pro-rich and pro-educated inequity is a public health
      challenge mainly in the older part of the population.

PMID- 23012327
TI  - Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role
      in the pathogenesis of chronic GVHD.
AB  - Chemokines regulate the migration of hemopoietic cells and play an important role
      in the pathogenesis of many immune-mediated diseases. Intradermal recruitment of
      CD8(+) T cells by CXCL10 is a central feature of the pathogenesis of cutaneous
      acute GVHD (aGVHD), but very little is known about the pathogenesis of chronic
      GVHD (cGVHD). Serum concentrations of the 3 CXCR3-binding chemokines, CXCL9,
      CXCL10, and CXCL11, were found to be markedly increased in patients with active
      cGVHD of the skin (n = 8). An 80% decrease in CD4(+) cells expressing CXCR3 was
      seen in the blood of these patients (n = 5), whereas CD4(+) cells were increased
      in tissue biopsies and were clustered around the central arterioles of the
      dermis. The well-documented increase in expression of CXCL10 in aGVHD therefore
      diversifies in cGVHD to include additional members of the CXCR3-binding family
      and leads to preferential recruitment of CD4(+) T cells. These observations
      reveal a central role for chemokine-mediated recruitment of CXCR3(+) T cells in
      cGVHD.

PMID- 23012326
TI  - Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after
      allogeneic stem cell transplantation.
AB  - Delays in immune recovery after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) are associated with increased risks of infection and
      relapse. IL-7 has a central role in T-cell development and survival and enhances
      immune recovery in murine models of allo-HSCT. We performed a phase 1 trial of r
      hIL-7 (CYT107) in recipients of T-cell depleted allo-HSCTs. Twelve patients were
      treated with escalating doses of r-hIL-7 administered weekly for 3 weeks. The
      study drug was well tolerated with only one patient developing acute skin GVHD.
      At baseline, patients were profoundly lymphopenic. CYT107 induced a doubling in
      CD4(+) and CD8(+) T cells. The main effect of IL-7 was an expansion of effector
      memory T cells, the predominant subset identified in our patients. There was no
      significant effect on CD4(+)CD25(+)FoxP3(+) T cells, NK, or B cells. Importantly,
      we not only saw quantitative increases in T cells after a short course of IL-7
      but also demonstrated an increase in functional T cells, including viral-specific
      T cells that recognize CMV. Enhanced TCR diversity was also observed after
      treatment. Our results indicate that r-hIL-7 can enhance immune recovery after a
      T cell-depleted allo-HSCT without causing significant GVHD or other serious
      toxicity (www.clinicaltrials.gov; NCT00684008).

PMID- 23012328
TI  - Terminal myeloid differentiation in vivo is induced by FLT3 inhibition in
      FLT3/ITD AML.
AB  - A hallmark of cancer is the disruption of differentiation within tumor cells.
      Internal tandem duplication mutations of the FLT3 kinase (FLT3/ITD) occur
      commonly in acute myeloid leukemia (AML) and are associated with poor survival,
      leading to efforts to develop FLT3 kinase inhibitors. However, FLT3 inhibitors
      have thus far met with limited success, inducing only a clearance of peripheral
      blasts with minimal BM responses. Quizartinib is a novel potent and selective
      FLT3 inhibitor currently being studied in clinical trials. In 13 of 14 FLT3/ITD
      AML patients with normal karyotype treated with quizartinib, we observed terminal
      myeloid differentiation of BM blasts in association with a clinical
      differentiation syndrome. The single patient whose blasts failed to differentiate
      had a preexisting C/EBPalpha mutation and another developed a C/EBPalpha mutation
      at disease progression, suggesting a mechanism of resistance to FLT3 inhibition.
      In vitro, in primary blasts cocultured with human BM stroma, FLT3 inhibition with
      quizartinib induced cell-cycle arrest and differentiation rather than apoptosis.
      The present study is the first description of terminal differentiation of cancer
      cells in patients treated with a tyrosine kinase inhibitor. These data highlight
      the importance of the differentiation block in the patho-genesis of AML.

PMID- 23012330
TI  - Disseminating results to clinical trial participants: a qualitative review of
      patient understanding in a post-trial population.
AB  - OBJECTIVE: To identify the most appropriate format for results dissemination to
      maximise understanding of trial results. DESIGN: Qualitative. SETTING: Of the
      original 58 4-T trial centres, 34 agreed to take part in this ancillary research.
      PARTICIPANTS: All participants from these centres were eligible. All 343
      participants were sent questionnaires. PRIMARY AND SECONDARY OUTCOME MEASURES:
      The low response rate meant that we were unable to make any firm conclusions
      about the patients' preferred method of dissemination; however, we were able to
      comment on the level of understanding demonstrated by the trial participants.
      RESULTS: All 40 (12%) returned questionnaires were received from 15 centres. We
      received no questionnaires from over half of the centres. The questionnaires
      which were returned demonstrated broad satisfaction with the results letter,
      general enthusiasm for the trial and a variable level of understanding of the
      results; however, there was a high proportion of responders who were not clear on
      why the research was undertaken or what the results meant. CONCLUSIONS: The low
      response rate may be related to delays during the trial set-up process suggesting
      that interest in a study quickly wanes for both patients and centres. From this
      we deduce that rapid dissemination of results is needed if it is to have any
      impact at all. The responders are likely to reflect a biased cohort who were both
      enthusiastic about the research and who had a good experience during their 3
      years in the 4-T trial. It is perhaps not surprising therefore that the overview
      is positive. That this population was still not fully informed about the purpose
      of the research would seem to confirm a low level of understanding among the
      general public which we suggest should be addressed during the consent process.

PMID- 23012329
TI  - Does the 'Scottish effect' apply to all ethnic groups? All-cancer, lung,
      colorectal, breast and prostate cancer in the Scottish Health and Ethnicity
      Linkage Cohort Study.
AB  - BACKGROUND AND OBJECTIVES: Although ethnic group variations in cancer exist, no
      multiethnic, population-based, longitudinal studies are available in Europe. Our
      objectives were to examine ethnic variation in all-cancer, and lung, colorectal,
      breast and prostate cancers.   DESIGN, SETTING, POPULATION, MEASURES AND
      ANALYSIS:  This retrospective cohort study of 4.65 million people linked the 2001
      Scottish Census (providing ethnic group) to cancer databases. With the White
      Scottish population as reference (value 100), directly age standardised rates and
      ratios (DASR and DASRR), and risk ratios, by sex and ethnic group with 95% CI
      were calculated for first cancers. In the results below, 95% CI around the DASRR
      excludes 100. Eight indicators of socio-economic position were assessed as
      potential confounders across all groups. RESULTS: For all cancers the White
      Scottish population (100) had the highest DASRRs, Indians the lowest (men 45.9
      and women 41.2) and White British (men 87.6 and women 87.3) and other groups were
      intermediate (eg, Chinese men 57.6). For lung cancer the DASRRs for Pakistani men
      (45.0), and women (53.5), were low and for any mixed background men high (174.5).
      For colorectal cancer the DASRRs were lowest in Pakistanis (men 32.9 and women
      68.9), White British (men 82.4 and women 83.7), other White (men 77.2 and women
      74.9) and Chinese men (42.6). Breast cancer in women was low in Pakistanis
      (62.2), Chinese (63.0) and White Irish (84.0). Prostate cancer was lowest in
      Pakistanis (38.7), Indian (62.6) and White Irish (85.4). No socio-economic
      indicator was a valid confounding variable across ethnic groups. CONCLUSIONS: The
      'Scottish effect' does not apply across ethnic groups for cancer. The findings
      have implications for clinical care, prevention and screening, for example,
      responding appropriately to the known low uptake among South Asian populations of
      bowel screening might benefit from modelling of cost-effectiveness of screening,
      given comparatively low cancer rates.

PMID- 23012331
TI  - Positive associations between consumerism and tobacco and alcohol use in early
      adolescence: cross-sectional study.
AB  - BACKGROUND: There is concern about the negative impact of modern consumer culture
      on young people's mental health, but very few studies have investigated
      associations with substance use. In those which have, positive associations have
      been attributed to attempts to satisfy the unmet needs of more materialistic
      individuals. OBJECTIVES: This study examines associations between different
      dimensions of consumerism and tobacco and alcohol use among Scottish early
      adolescents. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 2937 (92%
      of those eligible) secondary school pupils (ages 12-14) completed questionnaires
      in examination conditions. Analyses were restricted to those with complete data
      on all relevant variables (N=2736 smoking; N=2737 drinking). MEASURES: Dependent
      variables comprised ever smoking and current drinking. Measures of consumerism
      comprised number of 'premium' (range 0-7) and 'standard' (range 0-5) material
      possessions and three Consumer Involvement subscales, 'dissatisfaction',
      'consumer orientation' and 'brand awareness' (each range 3-12). Analyses also
      included school-year group and family affluence. RESULTS: Ever smoking and
      current drinking were both more prevalent among adolescents with more 'premium'
      and 'standard' material possessions, greater consumer 'dissatisfaction' and
      'brand awareness' (mutually adjusted analyses including school-year group and
      family affluence). The strongest relationships occurred for 'brand awareness':
      for each unit increase in 'brand awareness' the ORs (95% CI) of ever smoking were
      1.17 (1.08 to 1.26) and 1.23 (1.14 to 1.33) in males and females, respectively;
      and those for drinking were 1.15 (1.08 to 1.23) and 1.21 (1.13 to 1.30). 'Brand
      awareness' had an equal or stronger relationship with both smoking and drinking
      than did family affluence. CONCLUSIONS: These results suggest aassociations
      between consumerism and both smoking and drinking might arise because adolescent
      identities incorporate both consumerism and substance use, or be the result of
      promotion (indirectly in the case of tobacco) linking consumerist or aspirational
      lifestyles with these behaviours.

PMID- 23012333
TI  - In vivo and post-mortem memory circuit integrity in frontotemporal dementia and
      Alzheimer's disease.
AB  - Behavioural variant frontotemporal dementia can present with episodic memory
      deficits as severe as those in Alzheimer's disease. Little is known of the
      integrity of grey matter areas and white matter tracts of the Papez memory
      circuit in these diseases. The integrity of the Papez circuit (hippocampus,
      fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated
      in vivo and at post-mortem in behavioural variant frontotemporal dementia and
      Alzheimer's disease cohorts using voxel-based morphometry, diffusion tensor
      imaging and manual volumetric tracing. Our findings indicate that behavioural
      variant frontotemporal dementia and Alzheimer's disease show similar degrees of
      hippocampal atrophy in vivo, but patients with behavioural variant frontotemporal
      dementia show greater hippocampal atrophy at post-mortem, with the frontotemporal
      lobar degeneration with TDP-43 inclusions subtype being particularly affected.
      Cingulate cortex findings show an expected atrophy pattern with behavioural
      variant frontotemporal dementia being affected more anteriorly and Alzheimer's
      disease showing more posterior atrophy. More importantly, subcortical Papez
      circuit regions (fornix and anterior thalamus) were affected in behavioural
      variant frontotemporal dementia only, with atrophy in these regions determining
      the degree of amnesia in behavioural variant frontotemporal dementia. Hippocampal
      atrophy does not appear to be an efficient diagnostic marker for underlying
      behavioural variant frontotemporal dementia or Alzheimer's disease pathology,
      although for behavioural variant frontotemporal dementia, episodic memory
      deficits in conjunction with marked hippocampal atrophy emerge as potential
      biomarkers for frontotemporal lobar degeneration with TDP-43 inclusions
      pathology. Sub-regions of the Papez circuit were differentially affected in
      behavioural variant frontotemporal dementia and Alzheimer's disease with
      subcortical regions determining the degree of episodic memory deficits in
      behavioural variant frontotemporal dementia. Subcortical atrophy should be taken
      into account when establishing whether the severe amnesia observed in a patient
      is likely to be due to behavioural variant frontotemporal dementia or Alzheimer's
      disease pathology.

PMID- 23012332
TI  - Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease
      and rapid dementias: a longitudinal multicentre study over 10 years.
AB  - To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing,
      presents an important approach in the identification of Creutzfeldt-Jakob disease
      cases. However, one special point of criticism of 14-3-3 testing is the
      specificity in the differential diagnosis of rapid dementia. The constant
      observation of increased cerebrospinal fluid referrals in the national
      surveillance centres over the last years raises the concern of declining
      specificity due to higher number of cerebrospinal fluid tests performed in
      various neurological conditions. Within the framework of a European Community
      supported longitudinal multicentre study ('cerebrospinal fluid markers') we
      analysed the spectrum of rapid progressive dementia diagnoses, their potential
      influence on 14-3-3 specificity as well as results of other dementia markers
      (tau, phosphorylated tau and amyloid-beta(1-42)) and evaluated the specificity of
      14-3-3 in Creutzfeldt-Jakob disease diagnosis for the years 1998-2008. A total of
      29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other
      cerebrospinal fluid dementia markers in patients with rapid dementia and
      suspected Creutzfeldt-Jakob disease in the participating centres. In 10 731
      patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was
      analysed for Creutzfeldt-Jakob disease with respect to increasing cerebrospinal
      fluid tests per year and spectrum of differential diagnosis. Ring trials were
      performed to ensure the comparability between centres during the reported time
      period. Protein 14-3-3 test specificity remained high and stable in the diagnosis
      of Creutzfeldt-Jakob disease during the observed time period across centres
      (total specificity 92%; when compared with patients with definite diagnoses only:
      specificity 90%). However, test specificity varied with respect to differential
      diagnosis. A high 14-3-3 specificity was obtained in differentiation to other
      neurodegenerative diseases (95-97%) and non-neurological conditions (91-97%). We
      observed lower specificity in the differential diagnoses of acute neurological
      diseases (82-87%). A marked and constant increase in cerebrospinal fluid test
      referrals per year in all centres did not influence 14-3-3 test specificity and
      no change in spectrum of differential diagnosis was observed. Cerebrospinal fluid
      protein 14-3-3 detection remains an important test in the diagnosis of
      Creutzfeldt-Jakob disease. Due to a loss in specificity in acute neurological
      events, the interpretation of positive 14-3-3 results needs to be performed in
      the clinical context. The spectrum of differential diagnosis of rapid progressive
      dementia varied from neurodegenerative dementias to dementia due to acute
      neurological conditions such as inflammatory diseases and non-neurological
      origin.

PMID- 23012334
TI  - Menthol cigarettes and lung cancer mortality.

PMID- 23012335
TI  - Response to "menthol cigarettes and lung cancer mortality".

PMID- 23012340
TI  - Cases of organophosphate poisoning treated with high-dose of atropine in an
      intensive care unit and the novel treatment approaches.
AB  - Organophosphate poisoning is a life-threatening condition, which is being
      responsible for the symptoms due to cholinergic effects. Clinical status and
      blood levels of cholinesterase are used its diagnosis. While atropine and
      pralidoxime (PAM) appear as essential medications, hemofiltration treatments and
      lipid solutions have been widely studied in recent years. In this study, the
      importance of high-dose atropine therapy and early intervention and novel
      treatment approaches are discussed. Records of a total of 25 patients treated for
      organophosphate poisoning in the intensive care unit (ICU) between April 2007 and
      December 2011 were evaluated retrospectively. Of the 25 patients, 14 (56%) were
      male and 11 (44%) were female with a mean age of 34.8 +/- 17.66 years (range: 14
      77 years). The patients were most frequently admitted in June (n = 4) and July (n
      = 4) (16%). Of the 25 patients, 22 patients (88%) were poisoned by oral intake,
      two (8%) by inhalation, and one (4%) by dermal route. Of them, 20 patients (80%)
      took organophosphates intentionally for suicidal purposes, while five (20%) cases
      poisoned due to accidental exposure. The scores of Glasgow Coma Scale of nine
      patients (36%) were below 8 point upon admission to hospital. The highest dose of
      atropine given was 100 mg intravenously on admission and 100 mg/h/day during
      follow-up. The total dose given was 11.6 g/12 days. A total of 11 patients (44%)
      were on mechanical ventilation for a mean duration of 5.73 +/- 4.83 days. The
      mean duration of ICU stay was 6.52 +/- 4.80 days. Of all, 23 patients (92%) were
      discharged in good clinical condition and one patient (4%) was referred to
      another hospital. This study suggests that atropine can be administered until
      secretions disappear and intensive care should be exerted in follow-up of these
      patients. In addition, in case of necessity for high doses, sufficient amounts of
      atropine and PAM should be available in hospitals. 

PMID- 23012342
TI  - Health hazards associated with nanomaterials.
AB  - Nanotechnology is a major scientific and economic growth area and presents a
      variety of hazards for human health and environment. It is widely believed that
      engineered nanomaterials will be increasingly used in biomedical applications (as
      therapeutics and as diagnostic tools). However, before these novel materials can
      be safely applied in a clinical setting, their toxicity needs to be carefully
      assessed. Nanoscale materials often behave different from the materials with a
      larger structure, even when the basic material is same. Many mammals get exposed
      to these nanomaterials, which can reach almost every cell of the mammalian body,
      causing the cells to respond against nanoparticles (NPs) resulting in
      cytotoxicity and/or genotoxicity. The important key to understand the toxicity of
      nanomaterials is that their minute size, smaller than cellular organelles, allows
      them to penetrate the basic biological structures, disrupting their normal
      function. There is a wealth of evidence for the noxious and harmful effects of
      engineered NPs as well as other nanomaterials. The rapid commercialization of
      nanotechnology field requires thoughtful, attentive environmental, animal and
      human health safety research and should be an open discussion for broader
      societal impacts and urgent toxicological oversight action. While 'nanotoxicity'
      is a relatively new concept to science, this comprehensive review focuses on the
      nanomaterials exposure through the skin, respiratory tract, and gastrointestinal
      tract and their mechanism of toxicity and effect on various organs of the body. 

PMID- 23012341
TI  - DNA damage in human skin keratinocytes caused by multiwalled carbon nanotubes
      with carboxylate functionalization.
AB  - Water-soluble carbon nanotubes have been found to be one of the most promising
      nanomaterials in biological- and biomedical-based applications. However, there
      have been major concerns on their ability to cause cellular and DNA damages upon
      exposure. In this work, we explore the toxic effects of three multiwalled carbon
      nanotubes (MWCNTs: nonpurified, purified and carboxylate-functionalized) on human
      skin keratinocytes (HaCaT). Cytotoxicity tests using the conventional thiazolyl
      blue tetrazolium bromide (MTT) and the water-soluble tetrazolium (WST-1) assays
      for 0.5 or 24 h exposure to 20 MUg/mL of MWCNTs show that all three caused
      minimum cytotoxicity that is generally not statistically significant. Assessment
      of direct and oxidative DNA damages using both alkaline Comet assay and
      formamidopyrimidine DNA glycosylase-modified Comet assay reveals that the
      treatment with 20 MUg/mL of MWCNTs does not cause significant direct DNA damages,
      but causes great amount of oxidative DNA damages in HaCaT cells. The oxidative
      DNA damage reaches the maximum amount at 4 h of incubation in Dulbecco's minimum
      essential medium, but decreases to the minimum at 8 and 24 h of incubation,
      indicating repair of the oxidative damages by the intrinsic DNA repair mechanism
      of the cells.

PMID- 23012343
TI  - Patulin in apple juice and its risk assessments on albino mice.
AB  - The contamination of apple juice with patulin mycotoxin is a major risk factor in
      food safety. This study focuses to assess the biochemical and histopathological
      effects of patulin in apple juice samples collected from different outlets
      retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose
      level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to
      male albino mice. The exposure to contaminated samples revealed significant
      elevation of all the studied blood parameters (alanine aminotransferase,
      aspartate aminotransferase and alkaline phosphatase activities as well as
      creatinine, urea and uric acid contents). On the other hand, and with regard to
      the accumulated neuronal toxicity of the tested dose level, the toxic signs were
      recorded as significant increase in the aggressive and locomotor behavioral
      changes. In addition, the brain areas monoamines concentration revealed variable
      increased changes. The potential maximal changes in norepinephrine, dopamine and
      serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum,
      hippocampus, midbrain and pons and medulla were assessed. Moreover, the
      histological examination revealed degeneration and necrosis in liver tissues and
      degenerated glomeruli and hemorrhage between the tubules of the cortical region
      in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple
      juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally
      administered mice.

PMID- 23012345
TI  - Can emergency physicians predict severity and time away from work?
AB  - BACKGROUND: Emergency and primary care physicians are often asked to estimate
      patients' likely duration of sickness absence or temporary disability following
      work-related injury or illness. However, return to work is a complex interaction
      of multiple factors and often difficult to predict accurately. AIMS: To compare
      physician estimates of expected time away from work and severity of injury, made
      at the time of the initial presentation, with actual duration of temporary
      disability following work-related shoulder or knee injury. METHODS: Patients aged
      18-65 with work-related shoulder or knee injuries who attended one of three
      Edmonton Emergency Departments were recruited. For each participant the treating
      physician made an estimate of severity and expected time before they would return
      to their work. This was compared with information on actual temporary disability
      (TDdays) obtained from the Alberta Workers' Compensation Board (WCB) data.
      RESULTS: Over the study period, 443 (88%) of 501 patients were enrolled into the
      study; however, only 177 (35%) agreed to linking their data with WCB. Median
      TDdays increased with the physicians' estimates of both severity and likely
      temporary disability. Physicians tended to underestimate time off work for those
      with long duration of TDdays, but overestimated this for those with short
      durations. CONCLUSIONS: Emergency physicians' estimates of expected lost work
      time and severity of injury were correlated with actual temporary disability,
      although their accuracy was fairly low. Further work to define why differences
      between estimated and actual temporary disability occur could help physicians and
      others planning return to work.

PMID- 23012344
TI  - Yoga for reducing perceived stress and back pain at work.
AB  - BACKGROUND: Stress and back pain are two key factors leading to sickness absence
      at work. Recent research indicates that yoga can be effective for reducing
      perceived stress, alleviating back pain, and improving psychological well-being.
      AIMS: To determine the effectiveness of a yoga-based intervention for reducing
      perceived stress and back pain at work. METHODS: Participants were recruited from
      a British local government authority and randomized into a yoga group who
      received one 50 min Dru Yoga session each week for 8 weeks and a 20 min DVD for
      home practice and a control group who received no intervention. Baseline and end
      programme measurements of self-reported stress, back pain and psychological well
      being were assessed with the Perceived Stress Scale, Roland Morris Disability
      Questionnaire and the Positive and Negative Affect Scale. RESULTS: There were 37
      participants in each group. Analysis of variance and multiple linear regression
      showed that in comparison to the control group, the yoga group reported
      significant reductions in perceived stress and back pain, and a substantial
      improvement in psychological well-being. When compared with the control group at
      the end of the programme, the yoga group scores were significantly lower for
      perceived stress, back pain, sadness and hostility, and substantially higher for
      feeling self-assured, attentive and serene. CONCLUSIONS: The results indicate
      that a workplace yoga intervention can reduce perceived stress and back pain and
      improve psychological well-being. Larger randomized controlled trials are needed
      to determine the broader efficacy of yoga for improving workplace productivity
      and reducing sickness absence.

PMID- 23012346
TI  - Shortened menstrual cycles in LCD manufacturing workers.
AB  - BACKGROUND: Many chemical agents used in liquid crystal display (LCD)
      manufacturing have been evaluated in animal studies of female reproductive
      toxicity. Knowledge of their reproductive toxicity in humans is scant. AIMS: To
      determine the effect of organic solvents on menstrual cycle characteristics of
      workers in LCD manufacturing. METHODS: Cross-sectional study of female
      premenopausal workers in an LCD plant in Taiwan. Menstrual cycle characteristics
      were assessed from self-administered questionnaires, and chemical exposure was
      assessed using hand-held volatile organic compound (VOC) monitors with 24h
      canister sampling. RESULTS: There was a response rate of 94%, and the final study
      population after exclusions was 288. Canister sampling found many chemical
      compounds with potential reproductive effects in the fabrication areas of the
      plant. Concentrations of total VOC were higher in the panel and module
      fabrication areas than in other areas of the plant. The prevalence of short
      menstrual cycles (>24 days) was higher in panel workers (adjusted odds ratio
      [OR]: 7.68; 95% confidence interval [CI]: 1.51-39.15) and module workers
      (adjusted OR: 8.38; 95% CI: 1.72-40.95) than in array fabrication workers and
      office workers. CONCLUSIONS: We found evidence for a possible link between
      repeated exposure to multiple organic solvents such as ethanol and acetone and
      increased prevalence of short menstrual cycles in premenopausal women.

PMID- 23012347
TI  - An evaluation of low back pain among farmers in Ireland.
AB  - BACKGROUND: Low back pain (LBP) is the most commonly reported musculoskeletal
      disorder among farmers. There is limited research regarding LBP among farmers in
      Ireland. AIMS: To explore attributed causes of LBP, investigate the relationship
      between LBP and personal and work-related factors and measure the impact of LBP.
      METHODS: A questionnaire survey of Irish farmers was conducted on farmers from
      each of the main farm enterprise systems in Ireland. Data were analysed using chi
      square tests, t-tests, Mann-Whitney tests and logistic regression models.
      RESULTS: There were 600 farmers included in the survey with 100 from each of the
      six main farm systems. Lifting/pulling/pushing was identified as the most
      commonly attributed cause of LBP. In the multiple regression analysis the
      variables found to be associated with LBP included farm size and self-rated
      health. The odds ratios (OR) of LBP were greater among operators of medium and
      large farms [(OR = 1.52; 95% confidence interval (CI): 1.04-2.22 and OR = 1.86;
      95% CI: 1.16-3.98, respectively] compared with smaller farms (P < 0.05). Those
      who perceived health as 'good' (OR = 1.63; 95% CI: 1.14-2.33) by comparison with
      a rating of 'very good' had greater odds of LBP (P < 0.01). Some farmers changed
      work habits, sought help and needed time off work due to LBP. CONCLUSIONS:
      Lifting was identified as the main attributed cause for LBP. LBP leads to work
      disability that necessitated farmers changing work habits, getting help and
      needing time off work. In order to reduce LBP-related disability among farmers in
      the future, work practices involving lifting need to be further investigated.

PMID- 23012348
TI  - Factor structures for aggression and victimization among women who used
      aggression against male partners.
AB  - Theories and measures of women's aggression in intimate relationships are only
      beginning to be developed. This study provides a first step in conceptualizing
      the measurement of women's aggression by examining how well three widely used
      measures (i.e., the Revised Conflict Tactics Scales (CTS), the Sexual Experiences
      Survey [SES], and the Psychological Maltreatment of Women Inventory [PMWI])
      perform in assessing women's perpetration of and victimization by aggression in
      their intimate relationships with men. These constructs were examined in a
      diverse sample of 412 African American, Latina, and White women who had all
      recently used physical aggression against a male intimate partner. The factor
      structures and psychometric properties of perpetration and victimization models
      using these measures were compared. Results indicate that the factor structure of
      women's perpetration differs from that of women's victimization in theoretically
      meaningful ways. In the victimization model, all factors performed well in
      contributing to the measurement of the latent victimization construct. In
      contrast, the perpetration model performed well in assessing women's physical and
      psychological aggression but performed poorly in assessing women's sexual
      aggression, coercive control, and jealous monitoring. Findings suggest that the
      power and control model of intimate partner violence (IPV) may apply well to
      women's victimization but not as well to their perpetration of violence.

PMID- 23012349
TI  - A C-terminal membrane association domain of phototropin 2 is necessary for
      chloroplast movement.
AB  - Phototropins (phot1 and phot2), plant-specific blue light receptor kinases,
      mediate a range of physiological responses in Arabidopsis, including
      phototropism, chloroplast photorelocation movement, stomatal opening and leaf
      flattening. Phototropins consist of two photoreceptive domains at their N
      terminus, LOV1 (light, oxygen or voltage 1) and LOV2, and a serine/threonine
      kinase domain at their C-terminus. Here, we determined the molecular moiety for
      the membrane association of phototropins using the yeast CytoTrap and Arabidopsis
      protoplast systems. We then examined the physiological significance of the
      membrane association of phototropins. This detailed study with serial deletions
      narrowed down the association domain to a relatively small part of the C-terminal
      domain of phototropin. The functional analysis of phot2 deletion mutants in the
      phot2-deficient Adiantum and Arabidopsis mutants revealed that the ability to
      mediate the chloroplast avoidance response correlated well with phot2's membrane
      association, especially with the Golgi apparatus. Taken together, our data
      suggest that a small part of the C-terminal domain of phototropins is necessary
      not only for membrane association but also for the physiological activities that
      elicit phototropin-specific responses.

PMID- 23012350
TI  - Overexpression of MIZU-KUSSEI1 enhances the root hydrotropic response by
      retaining cell viability under hydrostimulated conditions in Arabidopsis
      thaliana.
AB  - Because of their sessile nature, plants evolved several mechanisms to tolerate or
      avoid conditions where water is scarce. The molecular mechanisms contributing to
      drought tolerance have been studied extensively, whereas the molecular mechanism
      underlying drought avoidance is less understood despite its importance. Several
      lines of evidence showed that the roots sense the moisture gradient and grow
      toward the wet area: so-called hydrotropism. We previously identified MIZU-KUSSEI
      (MIZ) 1 and MIZ2/GNOM as genes responsible for this process. To gain new insight
      into the molecular mechanism of root hydrotropism, we generated overexpressors of
      MIZ1 (MIZ1OEs) and analyzed their hydrotropic response. MIZ1OEs had a remarkable
      enhancement of root hydrotropism. Furthermore, a greater number of MIZ1OE root
      cells remained viable under hydrostimulated conditions than those of the wild
      type, which might contribute to retaining root growth under hydrostimulated
      conditions. Although overexpression of MIZ1 also caused a slight decrease in the
      root gravitropic response, it was not attributable to the enhanced hydrotropic
      response. In addition, miz2 mutation or the auxin response inhibitor nullified
      the enhanced hydrotropic response in MIZ1OEs. Furthermore, the expression of MIZ1
      did not alter the expression of typical genes involved in drought tolerance.
      These results suggest that MIZ1 positively regulates hydrotropism at an early
      stage and its overexpression results in an enhancement of signal transduction
      unique to root hydrotropism to increase the degree of hydrotropic root bending.

PMID- 23012351
TI  - MinD and MinE interact with anionic phospholipids and regulate division plane
      formation in Escherichia coli.
AB  - The Min proteins (MinC, MinD, and MinE) form a pole-to-pole oscillator that
      controls the spatial assembly of the division machinery in Escherichia coli
      cells. Previous studies identified that interactions of MinD with phospholipids
      positioned the Min machinery at the membrane. We extend these studies by
      measuring the affinity, kinetics, and ATPase activity of E. coli MinD, MinE, and
      MinDE binding to supported lipid bilayers containing varying compositions of
      anionic phospholipids. Using quartz crystal microbalance measurements, we found
      that the binding affinity (K(d)) for the interaction of recombinant E. coli MinD
      and MinE with lipid bilayers increased with increasing concentration of the
      anionic phospholipids phosphatidylglycerol and cardiolipin. The K(d) for MinD
      (1.8 MUM) in the presence of ATP was smaller than for MinE (12.1 MUM) binding to
      membranes consisting of 95:5 phosphatidylcholine/cardiolipin. The simultaneous
      binding of MinD and MinE to membranes revealed that increasing the concentration
      of anionic phospholipid stimulates the initial rate of adsorption (k(on)). The
      ATPase activity of MinD decreased in the presence of anionic phospholipids. These
      results indicate that anionic lipids, which are concentrated at the poles,
      increase the retention of MinD and MinE and explain its dwell time at this region
      of bacterial cells. These studies provide insight into interactions between MinD
      and MinE and between these proteins and membranes that are relevant to
      understanding the process of bacterial cell division, in which the interaction of
      proteins and membranes is essential.

PMID- 23012352
TI  - Targeting the unique methylation pattern of androgen receptor (AR) promoter in
      prostate stem/progenitor cells with 5-aza-2'-deoxycytidine (5-AZA) leads to
      suppressed prostate tumorigenesis.
AB  - Androgen receptor (AR) expression surveys found that normal prostate/prostate
      cancer (PCa) stem/progenitor cells, but not embryonic or mesenchymal stem cells,
      expressed little AR with high methylation in the AR promoter. Mechanism
      dissection revealed that the differential methylation pattern in the AR promoter
      could be due to differential expression of methyltransferases and binding of
      methylation binding protein to the AR promoter region. The low expression of AR
      in normal prostate/PCa stem/progenitor cells was reversed after adding 5-aza-2'
      deoxycytidine, a demethylating agent, which could then lead to decreased stemness
      and drive cells into a more differentiated status, suggesting that the
      methylation in the AR promoter of prostate stem/progenitor cells is critical not
      only in maintaining the stemness but also critical in protection of cells from
      differentiation. Furthermore, induced AR expression, via alteration of its
      methylation pattern, led to suppression of the self-renewal/proliferation of
      prostate stem/progenitor cells and PCa tumorigenesis in both in vitro assays and
      in vivo orthotopic xenografted mouse studies. Taken together, these data prove
      the unique methylation pattern of AR promoter in normal prostate/PCa
      stem/progenitor cells and the influence of AR on their renewal/proliferation and
      differentiation. Targeting PCa stem/progenitor cells with alteration of
      methylated AR promoter status might provide a new potential therapeutic approach
      to battle PCa because the PCa stem/progenitor cells have high tumorigenicity.

PMID- 23012353
TI  - Human histone H3K79 methyltransferase DOT1L protein [corrected] binds actively
      transcribing RNA polymerase II to regulate gene expression.
AB  - Histone-modifying enzymes play a pivotal role in gene expression and repression.
      In human, DOT1L (Dot1-like) is the only known histone H3 lysine 79
      methyltransferase. hDOT1L is associated with transcriptional activation, but the
      general mechanism connecting hDOT1L to active transcription remains largely
      unknown. Here, we report that hDOT1L interacts with the phosphorylated C-terminal
      domain of actively transcribing RNA polymerase II (RNAPII) through a region
      conserved uniquely in multicellular DOT1 proteins. Genome-wide profiling analyses
      indicate that the occupancy of hDOT1L largely overlaps with that of RNAPII at
      actively transcribed genes, especially surrounding transcriptional start sites,
      in embryonic carcinoma NCCIT cells. We also find that C-terminal domain binding
      or H3K79 methylations by hDOT1L is important for the expression of target genes
      such as NANOG and OCT4 and a marker for pluripotency in NCCIT cells. Our results
      indicate that a functional interaction between hDOT1L and RNAPII targets hDOT1L
      and subsequent H3K79 methylations to actively transcribed genes.

PMID- 23012354
TI  - A conformational change of the gamma subunit indirectly regulates the activity of
      cyanobacterial F1-ATPase.
AB  - The central shaft of the catalytic core of ATP synthase, the gamma subunit
      consists of a coiled-coil structure of N- and C-terminal alpha-helices, and a
      globular domain. The gamma subunit of cyanobacterial and chloroplast ATP synthase
      has a unique 30-40-amino acid insertion within the globular domain. We recently
      prepared the insertion-removed alpha(3)beta(3)gamma complex of cyanobacterial ATP
      synthase (Sunamura, E., Konno, H., Imashimizu-Kobayashi, M., and Hisabori, T.
      (2010) Plant Cell Physiol. 51, 855-865). Although the insertion is thought to be
      located in the periphery of the complex and far from catalytic sites, the mutant
      complex shows a remarkable increase in ATP hydrolysis activity due to a reduced
      tendency to lapse into ADP inhibition. We postulated that removal of the
      insertion affects the activity via a conformational change of two central alpha
      helices in gamma. To examine this hypothesis, we prepared a mutant complex that
      can lock the relative position of two central alpha-helices to each other by way
      of a disulfide bond formation. The mutant obtained showed a significant change in
      ATP hydrolysis activity caused by this restriction. The highly active locked
      complex was insensitive to N-dimethyldodecylamine-N-oxide, suggesting that the
      complex is resistant to ADP inhibition. In addition, the lock affected epsilon
      inhibition. In contrast, the change in activity caused by removal of the gamma
      insertion was independent from the conformational restriction of the central axis
      component. These results imply that the global conformational change of the gamma
      subunit indirectly regulates complex activity by changing both ADP inhibition and
      epsilon inhibition.

PMID- 23012355
TI  - Effect of zymogen domains and active site occupation on activation of prothrombin
      by von Willebrand factor-binding protein.
AB  - Prothrombin is conformationally activated by von Willebrand factor-binding
      protein (vWbp) from Staphylococcus aureus through insertion of the NH(2)-terminal
      residues of vWbp into the prothrombin catalytic domain. The rate of prothrombin
      activation by vWbp(1-263) is controlled by a hysteretic kinetic mechanism
      initiated by substrate binding. The present study evaluates activation of
      prothrombin by full-length vWbp(1-474) through activity progress curve analysis.
      Additional interactions from the COOH-terminal half of vWbp(1-474) strengthened
      the initial binding of vWbp to prothrombin, resulting in higher activity and an
      ~100-fold enhancement in affinity. The affinities of vWbp(1-263) or vWbp(1-474)
      were compared by equilibrium binding to the prothrombin derivatives prethrombin
      1, prethrombin 2, thrombin, meizothrombin, and meizothrombin(des-fragment 1) and
      their corresponding active site-blocked analogs. Loss of fragment 1 in
      prethrombin 1 enhanced affinity for both vWbp(1-263) and vWbp(1-474), with a 30
      45% increase in Gibbs free energy, implicating a regulatory role for fragment 1
      in the activation mechanism. Active site labeling of all prothrombin derivatives
      with D-Phe-Pro-Arg-chloromethyl ketone, analogous to irreversible binding of a
      substrate, decreased their K(D) values for vWbp into the subnanomolar range,
      reflecting the dependence of the activating conformational change on substrate
      binding. The results suggest a role for prothrombin domains in the
      pathophysiological activation of prothrombin by vWbp, and may reveal a function
      for autocatalysis of the vWbp.prothrombin complexes during initiation of blood
      coagulation.

PMID- 23012356
TI  - Identification of a karyopherin beta1/beta2 proline-tyrosine nuclear localization
      signal in huntingtin protein.
AB  - Among the known pathways of protein nuclear import, the karyopherin
      beta2/transportin pathway is only the second to have a defined nuclear
      localization signal (NLS) consensus. Huntingtin, a 350-kDa protein, has defined
      roles in the nucleus, as well as a CRM1/exportin-dependent nuclear export signal;
      however, the NLS and exact pathway of import have remained elusive. Here, using a
      live cell assay and affinity chromatography, we show that huntingtin has a
      karyopherin beta2-dependent proline-tyrosine (PY)-NLS in the amino terminus of
      the protein. This NLS comprises three consensus components: a basic charged
      sequence, a downstream conserved arginine, and a PY sequence. Unlike the classic
      PY-NLS, which has an unstructured intervening sequence between the consensus
      components, we show that a beta sheet structured region separating the consensus
      elements is critical for huntingtin NLS function. The huntingtin PY-NLS is also
      capable of import through the importin/karyopherin beta1 pathway but was not
      functional in all cell types tested. We propose that this huntingtin PY-NLS may
      comprise a new class of multiple import factor-dependent NLSs with an internal
      structural component that may regulate NLS activity.

PMID- 23012357
TI  - Bacillus anthracis thioredoxin systems, characterization and role as electron
      donors for ribonucleotide reductase.
AB  - Bacillus anthracis is the causative agent of anthrax, which is associated with a
      high mortality rate. Like several medically important bacteria, B. anthracis
      lacks glutathione but encodes many genes annotated as thioredoxins, thioredoxin
      reductases, and glutaredoxin-like proteins. We have cloned, expressed, and
      characterized three potential thioredoxins, two potential thioredoxin reductases,
      and three glutaredoxin-like proteins. Of these, thioredoxin 1 (Trx1) and NrdH
      reduced insulin, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), and the manganese
      containing type Ib ribonucleotide reductase (RNR) from B. anthracis in the
      presence of NADPH and thioredoxin reductase 1 (TR1), whereas thioredoxin 2 (Trx2)
      could only reduce DTNB. Potential TR2 was verified as an FAD-containing protein
      reducible by dithiothreitol but not by NAD(P)H. The recently discovered monothiol
      bacillithiol did not work as a reductant for RNR, either directly or via any of
      the redoxins. The catalytic efficiency of Trx1 was 3 and 20 times higher than
      that of Trx2 and NrdH, respectively, as substrates for TR1. Additionally, the
      catalytic efficiency of Trx1 as an electron donor for RNR was 7-fold higher than
      that of NrdH. In extracts of B. anthracis, Trx1 was responsible for almost all of
      the disulfide reductase activity, whereas Western blots showed that the level of
      Trx1 was 15 and 60 times higher than that of Trx2 and NrdH, respectively. Our
      findings demonstrate that the most important general disulfide reductase system
      in B. anthracis is TR1/Trx1 and that Trx1 is the physiologically relevant
      electron donor for RNR. This information may provide a basis for the development
      of novel antimicrobial therapies targeting this severe pathogen.

PMID- 23012358
TI  - Regulation of RhoA signaling by the cAMP-dependent phosphorylation of
      RhoGDIalpha.
AB  - RhoA plays a pivotal role in regulating cell shape and movement. Protein kinase A
      (PKA) inhibits RhoA signaling and thereby induces a characteristic morphological
      change, cell rounding. This has been considered to result from cAMP-induced
      phosphorylation of RhoA at Ser-188, which induces a stable RhoA-GTP-RhoGDIalpha
      complex and sequesters RhoA to the cytosol. However, few groups have shown RhoA
      phosphorylation in intact cells. Here we show that phosphorylation of RhoGDIalpha
      but not RhoA plays an essential role in the PKA-induced inhibition of RhoA
      signaling and in the morphological changes using cardiac fibroblasts. The
      knockdown of RhoGDIalpha by siRNA blocks cAMP-induced cell rounding, which is
      recovered by RhoGDIalpha-WT expression but not when a RhoGDIalpha-S174A mutant is
      expressed. PKA phosphorylates RhoGDIalpha at Ser-174 and the phosphorylation of
      RhoGDIalpha is likely to induce the formation of a active RhoA-RhoGDIalpha
      complex. Our present results thus reveal a principal molecular mechanism
      underlying G(s)/cAMP-induced cross-talk with G(q)/G(13)/RhoA signaling.

PMID- 23012359
TI  - Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the
      bladder epithelial cells and the bacterium-induced cytotoxicity: a possible
      function in urinary tract.
AB  - The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial
      surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a
      glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a
      lectin located at bacterial pili, and their interaction initiates UPEC infection.
      Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in
      various tissues besides the lung. However, the functions of SP-D in the non
      pulmonary tissues are poorly understood. The purposes of this study were to
      investigate the possible function of SP-D expressed in the bladder urothelium and
      the mechanisms by which SP-D functions. SP-D was expressed in human bladder
      mucosa, and its mRNA was increased in the bladder of the UPEC infection model in
      mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca(2+)
      dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial
      adherence to 5637 cells, the human bladder cell line, and the UPEC-induced
      cytotoxicity. In addition, preincubation of SP-D with 5637 cells resulted in the
      decreased adherence of UPEC to the cells and in a reduced number of cells injured
      by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding.
      Consistent with the in vitro data, the exogenous administration of SP-D inhibited
      UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice.
      These results support the conclusion that SP-D can protect the bladder urothelium
      against UPEC infection and suggest a possible function of SP-D in urinary tract.

PMID- 23012360
TI  - The leukocyte chemotactic receptor FPR1 is functionally expressed on human lens
      epithelial cells.
AB  - BACKGROUND: Lens degeneration in Fpr1(-/-) mice prompted us to search for
      functional FPR1 expression directly on lens epithelial cells. RESULTS: FPR1 is
      functionally expressed on human lens epithelial cells but has atypical properties
      compared with hematopoietic cell FPR1. CONCLUSION: Lens epithelial cell FPR1 may
      be involved in development and maintenance of the lens. SIGNIFICANCE: This is the
      first link between non-hematopoietic expression of FPR1 and an ophthalmologic
      phenotype. Formyl peptide receptor 1 (FPR1) is a G protein-coupled
      chemoattractant receptor expressed mainly on leukocytes. Surprisingly, aging
      Fpr1(-/-) mice develop spontaneous lens degeneration without inflammation or
      infection (J.-L. Gao et al., manuscript in preparation). Therefore, we
      hypothesized that FPR1 is functionally expressed directly on lens epithelial
      cells, the only cell type in the lens. Consistent with this, the human fetal lens
      epithelial cell line FHL 124 expressed FPR1 mRNA and was strongly FPR1 protein
      positive by Western blot and FACS. Competition binding using FPR1 ligands N
      formyl-Nle-Leu-Phe-Nle-Tyr-Lys (Nle = Norleucine),
      formylmethionylleucylphenylalanine, and peptide W revealed the same profile for
      FHL 124 cells, neutrophils, and FPR1-transfected HEK 293 cells. Saturation
      binding with fluorescein-labeled N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys revealed ~2500
      specific binding sites on FHL-124 cells (K(D) ~ 0.5 nm) versus ~40,000 sites on
      neutrophils (K(D) = 3.2 nm). Moreover, formylmethionylleucylphenylalanine induced
      pertussis toxin-sensitive Ca(2+) flux in FHL 124 cells, consistent with classic
      G(i)-mediated FPR1 signaling. FHL 124 cell FPR1 was atypical in that it resisted
      agonist-induced internalization. Expression of FPR1 was additionally supported by
      detection of the intact full-length open reading frame in sequenced cDNA from FHL
      124 cells. Thus, FHL-124 cells express functional FPR1, which is consistent with
      a direct functional role for FPR1 in the lens, as suggested by the phenotype of
      Fpr1 knock-out mice.

PMID- 23012361
TI  - Activity, specificity, and probe design for the smallpox virus protease K7L.
AB  - The K7L gene product of the smallpox virus is a protease implicated in the
      maturation of viral proteins. K7L belongs to protease Clan CE, which includes
      distantly related cysteine proteases from eukaryotes, pathogenic bacteria, and
      viruses. Here, we describe its recombinant high level expression, biochemical
      mechanism, substrate preference, and regulation. Earlier studies inferred that
      the orthologous I7L vaccinia protease cleaves at an AG-X motif in six viral
      proteins. Our data for K7L suggest that the AG-X motif is necessary but not
      sufficient for optimal cleavage activity. Thus, K7L requires peptides extended
      into the P7 and P8 positions for efficient substrate cleavage. Catalytic activity
      of K7L is substantially enhanced by homodimerization, by the substrate protein
      P25K as well as by glycerol. RNA and DNA also enhance cleavage of the P25K
      protein but not of synthetic peptides, suggesting that nucleic acids augment the
      interaction of K7L with its protein substrate. Library-based peptide preference
      analyses enabled us to design an activity-based probe that covalently and
      selectively labels K7L in lysates of transfected and infected cells. Our study
      thus provides proof-of-concept for the design of inhibitors and probes that may
      contribute both to a better understanding of the role of K7L in the virus life
      cycle and the design of novel anti-virals.

PMID- 23012362
TI  - Identification of molecular switch regulating interactions of Janus kinase 3 with
      cytoskeletal proteins.
AB  - Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase expressed in both
      hematopoietic and nonhematopoietic cells. Although mutations that abrogate Jak3
      functions cause different immunological disorders, its constitutive activation
      leads to various types of cancer. Previously, we demonstrated that Jak3
      interacted with actin-binding protein villin, thereby facilitating cytoskeletal
      remodeling and wound repair. In this study, we characterize the structural
      determinants that regulate the interactions between Jak3 and cytoskeletal
      proteins of the villin/gelsolin family. Functional reconstitution of kinase
      activity by recombinant full-length (wt) Jak3 using Jak3-wt or villin/gelsolin-wt
      as substrate showed that Jak3 autophosphorylation was the rate-limiting step
      during interactions between Jak3 and cytoskeletal proteins. Determination of
      kinetic parameters showed that phosphorylated (P) Jak3-wt binds to P-villin-wt
      with a dissociation constant (K(d)) of 23 nM and a Hill's coefficient of 3.7.
      Pairwise binding between Jak3 mutants and P-villin-wt showed that the FERM domain
      of Jak3 was sufficient for binding to P-villin-wt with a K(d) of 40.0 nM.
      However, the SH2 domain of Jak3 prevented P-villin-wt from binding to the FERM
      domain of nonphosphorylated protein. We demonstrate that the intramolecular
      interaction between the FERM and SH2 domains of nonphosphorylated Jak3 prevented
      Jak3 from binding to villin and that tyrosine autophosphorylation of Jak3 at the
      SH2 domain decreased these intramolecular interactions and facilitated binding of
      the FERM domain to villin. Thus we demonstrate the molecular mechanism of
      interactions between Jak3 and cytoskeletal proteins where tyrosine
      phosphorylation of the SH2 domain acted as an intramolecular switch for the
      interactions between Jak3 and cytoskeletal proteins.

PMID- 23012363
TI  - Formation and structure of a NAIP5-NLRC4 inflammasome induced by direct
      interactions with conserved N- and C-terminal regions of flagellin.
AB  - The NOD-like receptors NAIP5 and NLRC4 play an essential role in the innate
      immune response to the bacterial tail protein flagellin. Upon flagellin
      detection, NAIP5 and NLRC4 form a hetero-oligomeric inflammasome that induces
      caspase-1-dependent cell death. So far, both the mechanism of formation of the
      NAIP5-NLRC4 inflammasome and its structure are poorly understood. In this study
      we combine inflammasome reconstitution in HEK293 cells, purification of
      inflammasome components, and negative stain electron microscopy to address these
      issues. We find that a Salmonella typhimurium flagellin fragment comprising the
      D0 domain and the neighboring spoke region is able to co-precipitate NAIP5 and
      induce formation of the NAIP5-NLRC4 inflammasome. Comparison with smaller
      fragments indicates that flagellin recognition is mediated by its C-terminal
      residues as well as the spoke region. We reconstitute the inflammasome from
      purified flagellin, NAIP5, and NLRC4, thus proving that no other cellular
      components are required for its formation. Electron micrographs of the purified
      inflammasome provide unprecedented insight into its architecture, revealing disk
      like complexes consisting of 11 or 12 protomers in which NAIP5 and NLRC4 appear
      to occupy equivalent positions. On the basis of our data, we propose a model for
      inflammasome formation wherein direct interaction of flagellin with a single
      NAIP5 induces the recruitment and progressive incorporation of NLRC4, resulting
      in the formation of a hetero-oligomeric inflammasome.

PMID- 23012364
TI  - Copper starvation-inducible protein for cytochrome oxidase biogenesis in
      Bradyrhizobium japonicum.
AB  - Microarray analysis of Bradyrhizobium japonicum grown under copper limitation
      uncovered five genes named pcuABCDE, which are co-transcribed and co-regulated as
      an operon. The predicted gene products are periplasmic proteins (PcuA, PcuC, and
      PcuD), a TonB-dependent outer membrane receptor (PcuB), and a cytoplasmic
      membrane-integral protein (PcuE). Homologs of PcuC and PcuE had been discovered
      in other bacteria, namely PCu(A)C and YcnJ, where they play a role in cytochrome
      oxidase biogenesis and copper transport, respectively. Deletion of the pcuABCDE
      operon led to a pleiotropic phenotype, including defects in the aa(3)-type
      cytochrome oxidase, symbiotic nitrogen fixation, and anoxic nitrate respiration.
      Complementation analyses revealed that, under our assay conditions, the tested
      functions depended only on the pcuC gene and not on pcuA, pcuB, pcuD, or pcuE.
      The B. japonicum genome harbors a second pcuC-like gene (blr7088), which,
      however, did not functionally replace the mutated pcuC. The PcuC protein was
      overexpressed in Escherichia coli, purified to homogeneity, and shown to bind
      Cu(I) with high affinity in a 1:1 stoichiometry. The replacement of His(79),
      Met(90), His(113), and Met(115) by alanine perturbed copper binding. This
      corroborates the previously purported role of this protein as a periplasmic
      copper chaperone for the formation of the Cu(A) center on the aa(3)-type
      cytochrome oxidase. In addition, we provide evidence that PcuC and the copper
      chaperone ScoI are important for the symbiotically essential, Cu(A)-free cbb(3)
      type cytochrome oxidase specifically in endosymbiotic bacteroids of soybean root
      nodules, which could explain the symbiosis-defective phenotype of the pcuC and
      scoI mutants.

PMID- 23012365
TI  - Evidence for chemokine-mediated coalescence of preformed flotillin hetero
      oligomers in human T-cells.
AB  - We have shown previously that endogenous flotillin-1 and -2, closely related
      proteins implicated in scaffolding of membrane microdomains, are rapidly
      recruited to the uropods of chemoattractant-stimulated human neutrophils and T
      cells and are involved in cell polarization. Coexpressed flotillin-1 and -2, but
      not singly expressed proteins, are also targeted to the uropod of T-cells and
      neutrophils. Biochemical studies suggest formation of flotillin homo- and hetero
      oligomers in other cell types, but so far knowledge is lacking on in situ
      flotillin organization in leukocytes. We have now analyzed flotillin organization
      in human T-cells using fluorescence resonance energy transfer (FRET). Coexpressed
      C-terminally tagged flotillin-1-mCherry and flotillin-2-enhanced green
      fluorescent protein (EGFP) show significant FRET when analyzed in intact human T
      cells in the absence and presence of chemokine. In contrast, little FRET was
      observed between coexpressed flotillin-1-mCherry and flotillin-1-EGFP before or
      after chemokine addition, indicating predominant formation of heterodimers and/or
      -oligomers. Interestingly coexpression of untagged flotillin-2 strongly enhanced
      FRET between differently tagged flotillin-1 molecules in resting and chemokine
      stimulated cells, indicating that close contacts of flotillin-1 molecules only
      occur in flotillin-2-containing hetero-oligomers. Comparable results were
      obtained for tagged flotillin-2. We further show that disruption of the actin
      network, depletion of intracellular calcium, and inhibition of phospholipase C
      all result in suppression of chemokine-induced polarization and flotillin cap
      formation, but do not abolish FRET between tagged flotillin-1 and -2. Our results
      support predominant formation of flotillin-1 and -2 hetero-oligomers in resting
      and chemokine-stimulated human T-cells which may importantly contribute to
      structuring of the uropod.

PMID- 23012367
TI  - Sumoylation is important for stability, subcellular localization, and
      transcriptional activity of SALL4, an essential stem cell transcription factor.
AB  - SALL4 is a transcription factor that plays a key role in the maintenance and self
      renewal of embryonic stem cells and hematopoietic stem cells. Given that little
      is known about regulation of SALL4, we studied biochemical modifications of
      SALL4B, a major splicing variant of SALL4, and elucidated their biological
      function. SALL4B was primarily modified by ubiquitination when it was expressed
      in both Sf9 and HEK293T cells. A significant fraction of SALL4B was further
      modified by sumoylation when it was expressed in HEK293T cells. Constitutive SUMO
      modification of SALL4B was also detected in Tera-1, a cell line of the
      teratocarcinoma origin. SALL4B sumoylation was independent of ubiquitination and
      lysine residues 156, 316, 374, and 401 were essential for sumoylation. Chromatin
      fraction contained more SUMO-deficient SALL4B. Despite a shorter half-life than
      the wild-type counterpart, SUMO-deficient SALL4B interacted with OCT4 more
      efficiently than the wild-type SALL4B. RNAi-mediated silencing of SALL4
      expression caused significant down-regulation of both OCT4 and SOX2, which was
      rescued by ectopic expression of SALL4B but not by SUMO-deficient mutant.
      Significantly, compared with the wild-type SALL4B, SUMO-deficient mutant
      exhibited compromised trans-activation or trans-repression activities in reporter
      gene assays. Combined, our studies reveal sumoylation as a novel form of post
      translational modification for regulating the stability, subcellular
      localization, and transcriptional activity of SALL4.

PMID- 23012368
TI  - Oligonucleotide models of telomeric DNA and RNA form a Hybrid G-quadruplex
      structure as a potential component of telomeres.
AB  - Telomeric repeat-containing RNA, a non-coding RNA molecule, has recently been
      found in mammalian cells. The detailed structural features and functions of the
      telomeric RNA at human chromosome ends remain unclear, although this RNA molecule
      may be a key component of the telomere machinery. In this study, using model
      human telomeric DNA and RNA sequences, we demonstrated that human telomeric RNA
      and DNA oligonucleotides form a DNA-RNA G-quadruplex. We next employed chemistry
      based oligonucleotide probes to mimic the naturally formed telomeric DNA-RNA G
      quadruplexes in living cells, suggesting that the process of DNA-RNA G-quadruplex
      formation with oligonucleotide models of telomeric DNA and RNA could occur in
      cells. Furthermore, we investigated the possible roles of this DNA-RNA G
      quadruplex. The formation of the DNA-RNA G-quadruplex causes a significant
      increase in the clonogenic capacity of cells and has an effect on inhibition of
      cellular senescence. Here, we have used a model system to provide evidence about
      the formation of G-quadruplex structures involving telomeric DNA and RNA
      sequences that have the potential to provide a protective capping structure for
      telomere ends.

PMID- 23012366
TI  - Rac1 protein signaling is required for DNA damage response stimulated by
      topoisomerase II poisons.
AB  - To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin
      and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of
      histone H2AX (gammaH2AX) was analyzed using rat cardiomyoblast cells (H9c2).
      Etoposide caused a dose-dependent increase in the gammaH2AX level as shown by
      Western blotting. By contrast, the doxorubicin response was bell-shaped with high
      doses failing to increase H2AX phosphorylation. Identical results were obtained
      by immunohistochemical analysis of gammaH2AX focus formation, comet assay-based
      DNA strand break analysis, and measuring the formation of the topo II-DNA
      cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia
      mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug
      lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and
      etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and
      topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive
      manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2
      levels. DDR stimulated by topo II poisons was partially blocked by inhibition of
      type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan
      remained unaffected by lovastatin. The data show that the mechanisms involved in
      DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking
      DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1
      signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the
      formation of the topo II-DNA cleavable complex. Based on the data we suggest that
      Rac1-regulated mechanisms are required for DNA damage induction and subsequent
      activation of the DDR following treatment with topo II but not topo I poisons.

PMID- 23012369
TI  - Design, synthesis, structural and functional characterization of novel
      melanocortin agonists based on the cyclotide kalata B1.
AB  - BACKGROUND: Cyclotides are useful scaffolds to stabilize bioactive peptides.
      RESULTS: Four melanocortin analogues of kalata B1 were synthesized. One is a
      selective MC4R agonist. CONCLUSION: The analogues retain the native kalata B1
      scaffold and introduce a designed pharmacological activity, validating cyclotides
      as protein engineering scaffolds. SIGNIFICANCE: A novel type of melanocortin
      agonist has been developed, with potential as a drug lead for treating obesity.
      Obesity is an increasingly important global health problem that lacks current
      treatment options. The melanocortin receptor 4 (MC4R) is a target for obesity
      therapies because its activation triggers appetite suppression and increases
      energy expenditure. Cyclotides have been suggested as scaffolds for the insertion
      and stabilization of pharmaceutically active peptides. In this study, we explored
      the development of appetite-reducing peptides by synthesizing MC4R agonists based
      on the insertion of the His-Phe-Arg-Trp sequence into the cyclotide kalata B1.
      The ability of the analogues to fold similarly to kalata B1 but display MC4R
      activity were investigated. Four peptides were synthesized using t-butoxycarbonyl
      peptide chemistry with a C-terminal thioester to facilitate backbone cyclization.
      The structures of the peptides were found to be similar to kalata B1, evaluated
      by Halpha NMR chemical shifts. KB1(GHFRWG;23-28) had a K(i) of 29 nm at the MC4R
      and was 107 or 314 times more selective over this receptor than MC1R or MC5R,
      respectively, and had no detectable binding to MC3R. The peptide had higher
      affinity for the MC4R than the endogenous agonist, alpha-melanocyte stimulation
      hormone, but it was less potent at the MC4R, with an EC(50) of 580 nm for
      activation of the MC4R. In conclusion, we synthesized melanocortin analogues of
      kalata B1 that preserve the structural scaffold and display receptor binding and
      functional activity. KB1(GHFRWG;23-28) is potent and selective for the MC4R. This
      compound validates the use of cyclotides as scaffolds and has the potential to be
      a new lead for the treatment of obesity.

PMID- 23012370
TI  - Elastolytic mechanism of a novel M23 metalloprotease pseudoalterin from deep-sea
      Pseudoalteromonas sp. CF6-2: cleaving not only glycyl bonds in the hydrophobic
      regions but also peptide bonds in the hydrophilic regions involved in cross
      linking.
AB  - Elastin is a common insoluble protein that is abundant in marine vertebrates, and
      for this reason its degradation is important for the recycling of marine
      nitrogen. It is still unclear how marine elastin is degraded because of the
      limited study of marine elastases. Here, a novel protease belonging to the M23A
      subfamily, secreted by Pseudoalteromonas sp. CF6-2 from deep-sea sediment, was
      purified and characterized, and its elastolytic mechanism was studied. This
      protease, named pseudoalterin, has low identities (<40%) to the known M23
      proteases. Pseudoalterin has a narrow specificity but high activity toward
      elastin. Analysis of the cleavage sites of pseudoalterin on elastin showed that
      pseudoalterin cleaves the glycyl bonds in hydrophobic regions and the peptide
      bonds Ala-Ala, Ala-Lys, and Lys-Ala involved in cross-linking. Two peptic
      derivatives of desmosine, desmosine-Ala-Ala and desmosine-Ala-Ala-Ala, were
      detected in the elastin hydrolysate, indicating that pseudoalterin can dissociate
      cross-linked elastin. These results reveal a new elastolytic mechanism of the M23
      protease pseudoalterin, which is different from the reported mechanism where the
      M23 proteases only cleave glycyl bonds in elastin. Genome analysis suggests that
      M23 proteases may be popular in deep-sea sediments, implying their important role
      in elastin degradation. An elastin degradation model of pseudoalterin was
      proposed, based on these results and scanning electron microscopic analysis of
      the degradation by pseudoalterin of bovine elastin and cross-linked recombinant
      tropoelastin. Our results shed light on the mechanism of elastin degradation in
      deep-sea sediment.

PMID- 23012371
TI  - The molecular mechanism of thermostable alpha-galactosidases AgaA and AgaB
      explained by x-ray crystallography and mutational studies.
AB  - The alpha-galactosidase AgaA from the thermophilic microorganism Geobacillus
      stearothermophilus has great industrial potential because it is fully active at
      338 K against raffinose and can increase the yield of manufactured sucrose. AgaB
      has lower affinity for its natural substrates but is a powerful tool for the
      enzymatic synthesis of disaccharides by transglycosylation. These two enzymes
      have 97% identity and belong to the glycoside hydrolase (GH) family GH36 for
      which few structures are available. To understand the structural basis underlying
      the differences between these two enzymes, we determined the crystal structures
      of AgaA and AgaB by molecular replacement at 3.2- and 1.8 A-resolution,
      respectively. We also solved a 2.8-A structure of the AgaA(A355E) mutant, which
      has enzymatic properties similar to those of AgaB. We observe that residue 355 is
      located 20 A away from the active site and that the A355E substitution causes
      structural rearrangements resulting in a significant displacement of the
      invariant Trp(336) at catalytic subsite -1. Hence, the active cleft of AgaA is
      narrowed in comparison with AgaB, and AgaA is more efficient than AgaB against
      its natural substrates. The structure of AgaA(A355E) complexed with 1
      deoxygalactonojirimycin reveals an induced fit movement; there is a rupture of
      the electrostatic interaction between Glu(355) and Asn(335) and a return of
      Trp(336) to an optimal position for ligand stacking. The structures of two
      catalytic mutants of AgaA(A355E) complexed with raffinose and stachyose show that
      the binding interactions are stronger at subsite -1 to enable the binding of
      various alpha-galactosides.

PMID- 23012372
TI  - The HtrA protease from Streptococcus pneumoniae digests both denatured proteins
      and the competence-stimulating peptide.
AB  - The HtrA protease of Streptococcus pneumoniae functions both in a general stress
      response role and as an error sensor that specifically represses genetic
      competence when the overall level of biosynthetic errors in cellular proteins is
      low. However, the mechanism through which HtrA inhibits development of competence
      has been unknown. We found that HtrA digested the pneumococcal competence
      stimulating peptide (CSP) and constituted the primary extracytoplasmic CSP
      degrading activity in cultures of S. pneumoniae. Mass spectrometry demonstrated
      that cleavage predominantly followed residue Phe-8 of the CSP-1 isoform of the
      peptide within its central hydrophobic patch, and in competition assays, both CSP
      1 and CSP-2 interacted with HtrA with similar efficiencies. More generally,
      analysis of beta-casein digestion and of digestion within HtrA itself revealed a
      preference for substrates with non-polar residues at the P1 site. Consistent with
      a specificity for exposed hydrophobic residues, competition from native BSA only
      weakly inhibited digestion of CSP, but denaturation converted BSA into a strong
      competitive inhibitor of such proteolysis. Together these findings support a
      model in which digestion of CSP by HtrA is reduced in the presence of other
      unfolded proteins that serve as alternative targets for degradation. Such
      competition may provide a mechanism by which HtrA functions in a quality control
      capacity to monitor the frequency of biosynthetic errors that result in protein
      misfolding.

PMID- 23012373
TI  - Structural origins of DNA target selection and nucleobase extrusion by a DNA
      cytosine methyltransferase.
AB  - BACKGROUND: How DNA 5-cytosine methyltransferases (DCMTases) select their
      substrate nucleobase for extrusion from DNA duplex is poorly understood. RESULTS:
      The crystal structure of a pre-extrusion M.HaeIII DCMTase-substrate DNA complex
      is reported here. CONCLUSION: M.HaeIII selects its substrate cytosine for
      extrusion by selectively interfering with its stacking and hydrogen bonding
      interactions within the DNA duplex. SIGNIFICANCE: This is the first structural
      elucidation of the target cytosine selection by a DCMTase. Epigenetic methylation
      of cytosine residues in DNA is an essential element of genome maintenance and
      function in organisms ranging from bacteria to humans. DNA 5-cytosine
      methyltransferase enzymes (DCMTases) catalyze cytosine methylation via reaction
      intermediates in which the DNA is drastically remodeled, with the target cytosine
      residue extruded from the DNA helix and plunged into the active site pocket of
      the enzyme. We have determined a crystal structure of M.HaeIII DCMTase in complex
      with its DNA substrate at a previously unobserved state, prior to extrusion of
      the target cytosine and frameshifting of the DNA recognition sequence. The
      structure reveals that M.HaeIII selects the target cytosine and destabilizes its
      base-pairing through a precise, focused, and coordinated assault on the duplex
      DNA, which isolates the target cytosine from its nearest neighbors and thereby
      facilitates its extrusion from DNA.

PMID- 23012374
TI  - Thioredoxin, the processivity factor, sequesters an exposed cysteine in the thumb
      domain of bacteriophage T7 DNA polymerase.
AB  - Gene 5 protein (gp5) of bacteriophage T7 is a non-processive DNA polymerase. It
      achieves processivity by binding to Escherichia coli thioredoxin (trx). gp5/trx
      complex binds tightly to a primer-DNA template enabling the polymerization of
      hundreds of nucleotides per binding event. gp5 contains 10 cysteines. Under non
      reducing condition, exposed cysteines form intermolecular disulfide linkages
      resulting in the loss of polymerase activity. No disulfide linkage is detected
      when Cys-275 and Cys-313 are replaced with serines. Cys-275 and Cys-313 are
      located on loop A and loop B of the thioredoxin binding domain, respectively.
      Replacement of either cysteine with serine (gp5-C275S, gp5-C313S) drastically
      decreases polymerase activity of gp5 on dA(350)/dT(25). On this primer-template
      gp5/trx in which Cys-313 or Cys-275 is replaced with serine have 50 and 90%,
      respectively, of the polymerase activity observed with wild-type gp5/trx. With
      single-stranded M13 DNA as a template gp5-C275S/trx retains 60% of the polymerase
      activity of wild-type gp5/trx. In contrast, gp5-C313S/trx has only one-tenth of
      the polymerase activity of wild-type gp5/trx on M13 DNA. Both wild-type gp5/trx
      and gp5-C275S/trx catalyze the synthesis of the entire complementary strand of
      M13 DNA, whereas gp5-C313S/trx has difficulty in synthesizing DNA through sites
      of secondary structure. gp5-C313S fails to form a functional complex with trx as
      measured by the apparent binding affinity as well as by the lack of a physical
      interaction with thioredoxin during hydroxyapatite-phosphate chromatography.
      Small angle x-ray scattering reveals an elongated conformation of gp5-C313S in
      comparison to a compact and spherical conformation of wild-type gp5.

PMID- 23012375
TI  - Vitamin D suppression of endoplasmic reticulum stress promotes an antiatherogenic
      monocyte/macrophage phenotype in type 2 diabetic patients.
AB  - Cardiovascular disease is the leading cause of morbidity/mortality in patients
      with type 2 diabetes mellitus (T2DM), but there is a lack of knowledge about the
      mechanism(s) of increased atherosclerosis in these patients. In patients with
      T2DM, the prevalence of 25-hydroxy vitamin D (25(OH)D) deficiency is almost twice
      that for nondiabetics and doubles the relative risk of developing cardiovascular
      disease compared with diabetic patients with normal 25(OH)D. We tested the
      hypothesis that monocytes from vitamin D-deficient subjects will have a
      proatherogenic phenotype compared with vitamin D-sufficient subjects in 43
      patients with T2DM. Serum 25(OH)D level inversely correlated with monocyte
      adhesion to endothelial cells even after adjustment for demographic and
      comorbidity characteristics. Vitamin D-sufficient patients (>=30 ng/ml 25(OH)D)
      had lower monocyte endoplasmic reticulum (ER) stress, a predominance of M1 over
      M2 macrophage membrane receptors, and decreased mRNA expression of monocyte
      adhesion molecules PSGL-1, beta(1)-integrin, and beta(2)-integrin compared with
      patients with 25(OH)D levels of <30 ng/ml. In vitamin D-deficient macrophages,
      activation of ER stress increased adhesion and adhesion molecule expression and
      induced an M2-predominant phenotype. Moreover, adding 1,25(OH)(2)D(3) to vitamin
      D-deficient macrophages shifted their phenotype toward an M1-predominant
      phenotype with suppressed adhesion. Conversely, deletion of the vitamin D
      receptor in macrophages from diabetic patients activated ER stress, accelerated
      adhesion, and increased adhesion molecule expression. The absence of ER stress
      protein CCAAT enhancer-binding protein homologous protein suppressed monocyte
      adhesion, adhesion molecule expression, and the M2-predominant phenotype induced
      by vitamin D deficiency. Thus, vitamin D is a natural ER stress reliever that
      induced an antiatherogenic monocyte/macrophage phenotype.

PMID- 23012376
TI  - Bacterial biosynthetic gene clusters encoding the anti-cancer haterumalide class
      of molecules: biogenesis of the broad spectrum antifungal and anti-oomycete
      compound, oocydin A.
AB  - Haterumalides are halogenated macrolides with strong antitumor properties, making
      them attractive targets for chemical synthesis. Unfortunately, current synthetic
      routes to these molecules are inefficient. The potent haterumalide, oocydin A,
      was previously identified from two plant-associated bacteria through its high
      bioactivity against plant pathogenic fungi and oomycetes. In this study, we
      describe oocydin A (ooc) biosynthetic gene clusters identified by genome
      sequencing, comparative genomics, and chemical analysis in four plant-associated
      enterobacteria of the Serratia and Dickeya genera. Disruption of the ooc gene
      cluster abolished oocydin A production and bioactivity against fungi and
      oomycetes. The ooc gene clusters span between 77 and 80 kb and encode five
      multimodular polyketide synthase (PKS) proteins, a hydroxymethylglutaryl-CoA
      synthase cassette and three flavin-dependent tailoring enzymes. The presence of
      two free-standing acyltransferase proteins classifies the oocydin A gene cluster
      within the growing family of trans-AT PKSs. The amino acid sequences and
      organization of the PKS domains are consistent with the chemical predictions and
      functional peculiarities associated with trans-acyltransferase PKS. Based on
      extensive in silico analysis of the gene cluster, we propose a biosynthetic model
      for the production of oocydin A and, by extension, for other members of the
      haterumalide family of halogenated macrolides exhibiting anti-cancer, anti
      fungal, and other interesting biological properties.

PMID- 23012378
TI  - Canine distemper outbreak in pet store puppies linked to a high-volume dog
      breeder.
AB  - Canine distemper is uncommon in the pet trade in the United States, in large part
      due to effective vaccines against Canine distemper virus (CDV). This is a report
      of CDV affecting 24 young dogs of multiple breeds shortly after sale by 2 pet
      stores in Wyoming during August-October 2010. Cases were diagnosed over 37 days.
      Diagnosis was established by a combination of fluorescent antibody staining,
      reverse transcription polymerase chain reaction, negative stain electron
      microscopy, and necropsy with histopathology. Viral hemagglutinin gene sequences
      were analyzed from 2 affected dogs and were identical (GenBank accession no.
      JF283477). Sequences were distinct from those in a contemporaneous unrelated case
      of CDV in a Wyoming dog (JF283476) that had no contact with the pet store dogs.
      The breeding property from which the puppies originated was quarantined by the
      Kansas Animal Health Department. Puppies intended for sale were tested for CDV.
      Canine distemper was diagnosed on site in November 2010. At that point 1,466 dogs
      were euthanized to eliminate dispersal of the disease through commercial
      channels. The investigation underscores the risks inherent in large-scale dog
      breeding when vaccination and biosecurity practices are suboptimal.

PMID- 23012379
TI  - Fatal disseminated blastomycosis in a free-ranging American black bear (Ursus
      americanus).
AB  - An aged, free-ranging, female, radio-collared American black bear (Ursus
      americanus) died after an approximately 5 month long period of weight loss. Gross
      necropsy findings included severe diffuse pyogranulomatous bronchopneumonia,
      marked granulomatous lymphadenitis of tracheobronchial lymph nodes and multiple
      intra-abdominal lymph nodes, chronic focal jejunal ulceration, and widespread
      alopecia. Histopathologic examination revealed abundant fungal organisms
      morphologically compatible with Blastomyces sp. within pyogranulomatous
      inflammatory lesions in the lungs, multiple lymph nodes, liver, kidneys, jejunum,
      and right adrenal gland. In addition, the haircoat had a mild infestation of
      chewing lice (Trichodectes pinguis euarctidos), and large numbers of rhabditid
      nematodes consistent with Pelodera sp. were histologically observed within hair
      follicles.

PMID- 23012377
TI  - Regulation of cell adhesion and migration by Kindlin-3 cleavage by calpain.
AB  - Integrin activation on hematopoietic cells is essential for platelet aggregation,
      leukocyte adhesion, and transmigration through endothelium and extracellular
      matrix into inflamed tissues. To migrate through matrix, leukocyte integrin
      adhesion complexes undergo dynamic changes. Here we show that Kindlin-3, a main
      activator and binding partner of integrins in hematopoietic cells, can be cleaved
      by calpain in an activation-dependent manner. This calpain-mediated cleavage
      occurs in platelets and leukocytes as well as in endothelial cells. We determined
      the calpain I cleavage site in Kindlin-3 at tyrosine 373 in the N-terminal part
      of Kindlin-3 pleckstrin homology domain. Expression of the calpain-resistant
      Y373N mutant of Kindlin-3 promotes stronger cell adhesion to extracellular matrix
      under flow as well as to activated endothelium. In contrast, Y373N mutation in
      Kindlin-3 hinders cell migration. Mechanistically, calpain-resistant Y373N mutant
      of Kindlin-3 exhibited an activation-independent association with beta integrin
      cytoplasm domain. Thus, cleavage of Kindlin-3 by calpain controls the dynamics of
      integrin-Kindlin-3 interaction and as a result, integrin-dependent adhesion and
      migration of hematopoietic cells. This represents a novel mechanism regulating
      reversibility of integrin adhesion complexes in leukocytes, which, in turn, is
      critical for their successful transmigration through the extracellular matrix.

PMID- 23012380
TI  - Feline toxoplasmosis in Finland: cross-sectional epidemiological study and case
      series study.
AB  - Three subgroups of the Finnish cat population underwent investigation for
      different aspects of feline toxoplasmosis. Blood samples of 445 purebred pet cats
      and 45 shelter cats were screened for Toxoplasma gondii-specific immunoglobulin G
      antibodies with a direct agglutination test. The overall seroprevalence was
      48.4%; older cats and cats receiving raw meat in their diet were more often
      seropositive. Fecal samples were obtained from 131 shelters cats; 2 of the cats
      were found shedding T. gondii-like oocysts, and the oocysts shed by 1 of the 2
      were confirmed as T. gondii with polymerase chain reaction. Among 193 cats
      submitted for necropsy during a 3.5-year period, 6 (3.1%) had been diagnosed with
      generalized toxoplasmosis and were retrospectively further investigated. The main
      pathological lesions included acute interstitial pneumonia, acute necrotizing
      hepatitis, and nonsuppurative meningoencephalitis with glial granulomas.
      Immunohistochemical staining demonstrated a mild to massive parasite burden in
      tissues with pathological lesions as well as in unaffected tissues. The results
      of the direct multilocus genotyping of T. gondii parasites detected were
      consistent with endemic genotype II, and the causative parasite strains were
      isolated from 2 of the generalized toxoplasmosis cases. The results indicate that
      cats in Finland commonly encounter T. gondii and contribute to the environmental
      oocyst burden, while the endemic genotype II can also prove fatal to the
      parasite's definitive host. Preventing feline T. gondii infections is not only of
      public health importance but also a welfare issue for the cats themselves.

PMID- 23012381
TI  - Development of latex agglutination test for rapid detection of antibodies against
      Bovine herpesvirus 1 and Bovine herpesvirus 5 in cattle.
AB  - A latex agglutination test (LAT) based on sensitized polystyrene beads with
      inactivated Bovine herpesvirus 1 (BHV-1) particles was developed to detect serum
      antibodies against BHV-1 and Bovine herpesvirus 5 (BHV-5). Compared with a virus
      neutralization test using 252 serum samples, the sensitivity and specificity were
      94.7% and 97.5%, respectively. Finally, 512 clinical serum samples from 3 major
      cattle-breeding provinces were monitored, and the overall positive rate was
      34.57% (95% confidence interval: 30.45-38.69%). The results suggest that LAT has
      the potential to be a rapid method for the diagnosis of BHV-1 and BHV-5 infection
      in cattle herds.

PMID- 23012382
TI  - Intranasal fentanyl spray: a novel dosage form for the treatment of breakthrough
      cancer pain.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy,
      adverse events, dosing, and administration of intranasal fentanyl spray in the
      treatment of breakthrough cancer pain (BTCP) in adults. DATA SOURCES: Relevant
      published data were identified using PubMed from inception to April 2012 using
      the search terms fentanyl nasal spray, intranasal fentanyl, intranasal fentanyl
      cancer pain, and fentanyl pectin cancer pain. Only articles evaluating the use of
      intranasal fentanyl spray for cancer pain were selected. STUDY SELECTION AND DATA
      EXTRACTION: All articles evaluating the pharmacokinetics of intranasal fentanyl
      or the clinical efficacy of intranasal fentanyl spray for the treatment of BTCP
      were considered; references of selected articles were manually reviewed to
      identify further articles. The manufacturer of intranasal fentanyl spray was also
      contacted to obtain information. DATA SYNTHESIS: Intranasal fentanyl spray gained
      Food and Drug Administration approval for the treatment of BTCP in adults with
      cancer receiving stable background opioid therapy for chronic pain. In doses
      ranging from 100 to 800 MUg/spray, intranasal fentanyl spray was found to be more
      effective than placebo and more effective than oral morphine or oral fentanyl
      formulations in reducing pain for up to 15-45 minutes; onset of analgesia was
      also improved with intranasal fentanyl spray. The most commonly observed adverse
      events included nausea, vomiting, vertigo, and dizziness. CONCLUSIONS: For the
      treatment of BTCP, intranasal fentanyl spray offers improved onset of analgesia
      compared to other oral therapies; this improved onset of analgesia may closely
      mimic the typical time course of a BTCP episode. Nasal administration may
      overcome problems such as nausea, vomiting, or xerostomia that may complicate
      oral administration of analgesics. Potential disadvantages include uncertainty in
      treating more than 4 BTCP episodes per 24 hours and a higher cost compared to
      generically available oral opioid analgesics.

PMID- 23012383
TI  - The use of galactogogues in the breastfeeding mother.
AB  - OBJECTIVE: To review data regarding the efficacy of galactogogues available in
      the US to increase breast milk production in postpartum mothers. DATA SOURCES:
      Literature was sought using PubMed (1966-June 2012) and EMBASE (1973-June 2012).
      Search terms included breastfeeding, breast milk, lactation, galactogogue,
      metoclopramide, oxytocin, fenugreek, milk thistle, silymarin, growth hormone,
      thyroid releasing hormone, medroxyprogesterone, domperidone, goat's rue, beer,
      Asparagus racemosus, shatavari, Medicago sativa, alfalfa, Onicus benedictus,
      blessed thistle, Galega officinalis, brewer's yeast, and herbals. STUDY SELECTION
      AND DATA EXTRACTION: All studies including humans and published in English with
      data assessing the efficacy of galactogogues for increasing breast milk
      production were evaluated. DATA SYNTHESIS: Breast milk is considered the optimal
      food source for newborns through 1 year of age. Many factors influence overall
      maternal production, including maternal pain, illness, balance of time when
      returning to work, anxiety, or emotional stress. Although a variety of herbal and
      pharmaceutical options have anecdotal evidence of their ability to improve breast
      milk production, peer-reviewed studies proving their efficacy are lacking.
      Metoclopramide, oxytocin, fenugreek, and milk thistle have shown mixed results in
      improving milk production; however, the trials were small and had a variety of
      limitations. CONCLUSIONS: Nonpharmacologic recommendations should be exhausted
      before adding therapy. Although anecdotal evidence encourages the use of
      metoclopramide, fenugreek, asparagus, and milk thistle for their galactogogue
      properties, efficacy and safety data in the literature are lacking. Oxytocin and
      domperidone are potentially available for compounding purposes, but safety data
      are limited. More studies are needed to evaluate the effects of available
      galactogogues on breast milk production.

PMID- 23012384
TI  - Desensitization to inhaled aztreonam lysine in an allergic patient with cystic
      fibrosis using a novel approach.
AB  - OBJECTIVE: To report the successful desensitization of a highly allergic patient
      with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of
      intravenous desensitization followed by full-dose inhaled therapy without any
      adverse reactions. CASE SUMMARY: A 19-year-old woman with CF had persistent
      Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity
      reactions to multiple medications, including aztreonam and tobramycin
      (intravenous and inhaled). To start therapy with an inhaled antipseudomonal
      antibiotic on a chronic basis, she underwent rapid desensitization to intravenous
      aztreonam followed by initiation of inhaled aztreonam lysine. Following
      intravenous desensitization with aztreonam, there was no adverse reaction or
      decline in lung function noted with inhaled aztreonam lysine and the chronic
      therapy was continued at home, with a modified regimen to maintain
      desensitization. DISCUSSION: Aztreonam lysine has been used for treatment of
      patients with CF with chronic P. aeruginosa colonization. Previous allergic
      reaction to intravenous aztreonam is considered a contraindication for use of
      aztreonam lysine. Our patient had a history of hives and facial swelling
      following administration of intravenous aztreonam (type I hypersensitivity
      reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be
      done for drugs that mediate a type I hypersensitivity reaction, with mast cells
      and basophils being the cellular targets. There are a few case reports of
      desensitization to inhaled antibiotics such as tobramycin and colistin, but
      desensitization to aztreonam lysine has not previously been reported.
      CONCLUSIONS: Desensitization of a patient with CF who is allergic to intravenous
      aztreonam was successfully accomplished with the novel approach of rapid
      intravenous desensitization followed by inhaled therapy. As inhaled antibiotics
      are being increasingly used for patients with CF, this novel strategy can be used
      for desensitizing allergic patients with CF to ensure that they can continue to
      receive these medications safely.

PMID- 23012385
TI  - Pharmacokinetics and monte carlo simulations of doripenem in patients with
      febrile neutropenia.
AB  - BACKGROUND: Doripenem is a group 2 carbapenem with enhanced in vitro activity
      against gram-negative bacteria including Pseudomonas aeruginosa. There is a
      paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with
      febrile neutropenia. OBJECTIVE: To conduct a pharmacokinetic evaluation of 2
      doses of doripenem in patients with febrile neutropenia and provide probability
      estimates of attaining effective drug exposure against common gram-negative
      pathogens. METHODS: We obtained multiple blood samples from 12 adults with
      febrile neutropenia who were receiving either 500 mg or 1000 mg of intravenous
      doripenem over 4 hours every 8 hours. Following at least 2 doses, serum
      concentrations were measured in each subject at 1, 4, 6, and 8 hours after
      initiation of a dose by a validated high-performance liquid chromatography assay.
      The derived pharmacokinetic parameters from these serum levels were used to
      perform a 5000-patient Monte Carlo simulation against bacteria with minimal
      inhibitory concentrations (MICs) of 0.008-64 mg/L to determine probability
      estimates of the time in which unbound drug concentrations remain above the MIC
      (fT(>MIC)). RESULTS: The mean pharmacokinetic parameters in these patients were a
      volume of distribution of 43.9 L, an elimination rate constant of 0.37 h(-1), a
      total clearance of 14.4 L/h, and an area under the concentration-time curve of
      57.6 mg*h/L. An optimal probability of target attainment (40% fT(>MIC)) of 90%
      was obtained against bacteria with MICs <=2 mg/L and <=4 mg/L with 500-mg and
      1000-mg doses, respectively. Adverse events associated with doripenem were not
      observed. CONCLUSIONS: The findings from this analysis of doripenem suggest that
      higher doses, as well as prolonged infusions, may be necessary to optimally treat
      selected gram-negative bacteria (eg, P. aeruginosa) in patients with febrile
      neutropenia.

PMID- 23012386
TI  - Diagnostic exercise: Submucosal gastric masses in a cat.
AB  - A 14-year-old neutered male cat presenting with chronic vomiting had 2 masses
      within the submucosa of the stomach that were excised. They presented
      histologically as circumscribed, submucosal masses consisting of diffusely
      arranged medium-sized round cells with a moderate amount of cytoplasm and
      interspersed eosinophils, separated by trabecular fibroblastic stroma. The
      overlying mucosa was diffusely infiltrated by the same round cells, and marked
      epitheliotropism was present. Neoplastic cells labelled positive for CD3 and
      negative for CD79a and CD117. Giemsa staining and silver staining (SNOBA) were
      also negative. A T-cell lymphoma with reactive fibroplasia was diagnosed, and
      differential diagnoses including mast cell tumor and feline gastrointestinal
      eosinophilic sclerosing fibroplasia could be excluded.

PMID- 23012387
TI  - Endothelial binding of beta toxin to small intestinal mucosal endothelial cells
      in early stages of experimentally induced Clostridium perfringens type C
      enteritis in pigs.
AB  - Beta toxin (CPB) is known to be an essential virulence factor in the development
      of lesions of Clostridium perfringens type C enteritis in different animal
      species. Its target cells and exact mechanism of toxicity have not yet been
      clearly defined. Here, we evaluate the suitability of a neonatal piglet jejunal
      loop model to investigate early lesions of C. perfringens type C enteritis.
      Immunohistochemically, CPB was detected at microvascular endothelial cells in
      intestinal villi during early and advanced stages of lesions induced by C.
      perfringens type C. This was first associated with capillary dilatation and
      subsequently with widespread hemorrhage in affected intestinal segments. CPB was,
      however, not demonstrated on intestinal epithelial cells. This indicates a
      tropism of CPB toward endothelial cells and suggests that CPB-induced endothelial
      damage plays an important role in the early stages of C. perfringens type C
      enteritis in pigs.

PMID- 23012388
TI  - Phase difference between serum prolactin and cortisol rhythms is related to body
      mass index in humans.
AB  - BACKGROUND: Prolactin (PRL) has many effects in animals and man. For example, it
      regulates fat mass in fish, birds, and mammals. In particular, the timing of the
      serum PRL acrophase in relation to the light-dark cycle or to serum cortisol in
      constant light conditions determines whether the fat mass increases or decreases,
      as part of the adaptation to seasons. The role of PRL in this respect has been
      less well studied in man. HYPOTHESIS: We hypothesized that the timing of the PRL
      acrophase (time point of peak amplitude of the rhythm) with respect to that of
      cortisol may be correlated with fat mass [or body mass index (BMI) as proxy] in
      the human, as observed in animals. SUBJECTS: Seventy-four subjects were available
      [mean age, 43 (22-77) yr; mean BMI, 26.8 (18.7-38.4) kg/m(2)]. MEASURES:
      Immunofluorometric PRL assay and cortisol RIA of 10-min blood samples collected
      for 24 h were followed by cosinor analysis for the estimation of the acrophase.
      RESULTS: The time difference between the cortisol and PRL acrophases was
      positively correlated with BMI (P = 0.002), but not with sex, age, or season.
      CONCLUSION: In various species, a wide gap between the serum cortisol acrophase
      and that of PRL leads to fat storage. Our finding is consistent with this
      observation, although we used BMI as proxy. If an advance shift of the PRL
      acrophase in relation to that of cortisol is indeed responsible for increased fat
      mass in man, manipulating the PRL phase may offer an alternative means to treat
      obesity.

PMID- 23012389
TI  - Polycystic ovary syndrome is associated with higher left ventricular mass index:
      the CARDIA women's study.
AB  - OBJECTIVE: The aim of the study was to determine whether young women with
      polycystic ovary syndrome (PCOS) have evidence of early structural changes in
      echocardiographic parameters as a measurement of cardiovascular risk. METHODS: We
      investigated the association of PCOS and echocardiographic parameters in 984
      black and white women in the Coronary Artery Risk Development in Young Adults
      (CARDIA) study, a cohort followed prospectively for 20 yr. Women ages 34-46 (Year
      16) completed questionnaires recalling symptoms of oligomenorrhea and hirsutism
      in their 20s and 30s. Serum androgens were obtained at Year 2. Women in their 20s
      and 30s were classified into four mutually exclusive groups: 1) PCOS; 2) isolated
      oligomenorrhea (IO); 3) isolated hyperandrogenism (IH); and 4) reference group.
      Outcome measures were defined as echocardiography data from Year 5. We used
      multivariable linear regression models to evaluate the association of PCOS and
      its components with left ventricular (LV) mass index, left atrial (LA) diameter,
      LV ejection fraction (LVEF), and mitral inflow early wave to late wave ratio.
      RESULTS: Among 984 participants, 42 women (4.3%) were classified as PCOS, 67
      (6.8%) as IO, and 178 (18.0%) as IH. In multivariable linear regression analyses,
      women with PCOS had a 3.14 g/m(2.7) (95% confidence interval, 0.48-5.81) higher
      LV mass index compared to the reference group (approximately 10% higher). PCOS
      women also had a 0.11 cm/m (95% confidence interval, 0.02-0.19) larger LA
      diameter, after adjustment for age and race. CONCLUSION: PCOS, but not IO or IH,
      is associated with a higher LV mass index and larger LA diameter in young women,
      suggestive of early adverse cardiac remodeling. Additional longitudinal studies
      are needed to evaluate whether this difference persists over time.

PMID- 23012390
TI  - Stimulation of GPR30 increases release of EMMPRIN-containing microvesicles in
      human uterine epithelial cells.
AB  - CONTEXT: Uterine remodeling is highly dependent on the glycosylated transmembrane
      protein extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN). Previous
      studies indicate estradiol can increase EMMPRIN expression in uterine cells and
      promote subsequent induction of MMP production. OBJECTIVE: The aim of this study
      was to investigate the role of G protein-coupled receptor 30 (GPR30) stimulation
      on EMMPRIN microvesicle release in the human uterine epithelial cell line hTERT
      EEC (EECs). DESIGN: We examined EMMPRIN release by human EECs in response to
      GPR30 stimulation by microvesicle isolation, Western blot, and
      immunocytochemistry. We employed a pharmacological approach using the GPR30
      selective agonist G1 and the antagonist G15 to determine the receptor specificity
      of this response. RESULTS: We demonstrated GPR30 expression in EECs and release
      of EMMPRIN in microvesicles in response to stimulation of GPR30. G1, estradiol,
      and cholera toxin stimulated EMMPRIN release in microvesicles as detected by
      Western blot and immunocytochemistry, indicating that stimulation of GPR30 can
      induce EMMPRIN microvesicle release. CONCLUSIONS: These data indicate that
      EMMPRIN release in microvesicles can be mediated by stimulation of GPR30 in human
      EECs, suggesting that inappropriate stimulation or expression of this receptor
      may be significant in uterine pathology.

PMID- 23012392
TI  - Somatic mutations in the KCNJ5 gene raise the lateralization index: implications
      for the diagnosis of primary aldosteronism by adrenal vein sampling.
AB  - CONTEXT: Somatic mutations in the selectivity filter of KCNJ5 K(+) channel were
      found to be associated with higher plasma aldosterone concentrations in the
      patients with an aldosterone-producing adenoma (APA). OBJECTIVE: We investigated
      whether plasma aldosterone levels and the lateralization index are higher from
      the side with the APA with the mutation, as compared with those without the
      mutation. DESIGN: From 170 consecutive APA patients with comprehensive clinical
      and KCNJ5 data and a conclusive diagnosis, we recruited 91 patients with adrenal
      vein sampling and follow-up data. We measured CYP11B1 and CYP11B2 mRNA in APA
      tissue and plasma aldosterone (PAC) and plasma cortisol concentrations (PCC) in
      adrenal vein blood. To determine whether KCNJ5 mutations affected aldosterone
      output from the APA, we calculated the lateralization index (defined as the ratio
      of PAC to PCC at the APA side over the PAC to PCC ratio at the contralateral
      side). We also calculated two indexes of the aldosterone production from the APA
      side and the contralateral suppression index. RESULTS: The mRNA content of
      CYP11B2, but not of CYP11B1, and, accordingly, the lateralization index was
      higher (29.9 +/- 7.4 vs. 10.3 +/- 3.6, P < 0.02) in the APA with the mutation
      than in the APA without the mutation. CONCLUSIONS: APA patients with the somatic
      KCNJ5 mutations showed a higher production of aldosterone than those without such
      mutations, which translates in a higher lateralization index. Thus, they are more
      likely to be identified at adrenal vein sampling and therefore to receive
      adrenalectomy.

PMID- 23012391
TI  - Adipose tissue dysfunction in humans: a potential role for the transmembrane
      protein ENPP1.
AB  - CONTEXT: Adipose tissue (AT) helps to regulate body fat partitioning and systemic
      lipid/glucose metabolism. We have recently reported lipid/glucose metabolism
      abnormalities and increased liver triglyceride content in an AT-selective
      transgenic model overexpressing ectonucleotide pyrophosphatase/phosphodiesterase
      1 (ENPP1), the AdiposeENPP1-Tg mouse. OBJECTIVE: The aim of the study was to test
      the translational hypothesis that AT-ENPP1 overexpression associates with AT
      dysfunction (changes in AT gene expression, plasma fatty acid, and adipokine
      levels), increased liver triglyceride deposition, and systemic insulin resistance
      in humans. DESIGN/SETTING/PARTICIPANTS: A total of 134 young normoglycemic men
      and women were subjected to body composition studies, hyperinsulinemic-euglycemic
      clamps, and AT needle biopsy. Twenty men also had liver/muscle nuclear magnetic
      resonance spectroscopy. MAIN OUTCOME MEASURES: Predetermined measures included AT
      expression of ENPP1 and other lipid metabolism/inflammation genes, plasma
      adipokines, and nonesterified fatty acid (NEFA) levels, liver/muscle triglyceride
      content, and the systemic glucose disposal rate. RESULTS: After statistical
      adjustment for body fat content, increasing AT-ENPP1 was associated with up
      regulation of genes involved in NEFA metabolism and inflammation, increased
      postabsorptive NEFA levels, decreased plasma adiponectin, increased liver
      triglyceride content, and systemic insulin resistance in men. In women, there
      were no changes in plasma adiponectin, NEFAs, or glucose disposal rate associated
      with increasing AT-ENPP1, despite increased expression of lipid metabolism and
      inflammation genes in AT. CONCLUSIONS: Increased AT-ENPP1 is associated with AT
      dysfunction, increased liver triglyceride deposition, and systemic insulin
      resistance in young normoglycemic men. These findings are concordant with the
      AdiposeENPP1-Tg phenotype and identify a potential target of therapy for health
      complications of AT dysfunction, including type 2 diabetes and cardiovascular
      disease.

PMID- 23012393
TI  - Perspectives for improved and more accurate classification of canine mammary
      gland neoplasms.

PMID- 23012394
TI  - Endometrial response of beef heifers on day 7 following insemination to
      supraphysiological concentrations of progesterone associated with superovulation.
AB  - Ovarian stimulation is a routine procedure in assisted reproduction to stimulate
      the growth of multiple follicles in naturally single-ovulating species including
      cattle and humans. The aim of this study was to analyze the changes induced in
      the endometrial transcriptome associated with superovulation in cattle and place
      these observations in the context of our previous data on changes in the
      endometrial transcriptome associated with elevated progesterone (P4)
      concentrations within the physiological range and those changes induced in the
      embryo due to superovulation. Mean serum P4 concentrations were significantly
      higher from day 4 to day 7 in superovulated compared with unstimulated control
      heifers (P < 0.05). Between-group analysis revealed a clear separation in the
      overall transcriptional profile of endometria from unstimulated control heifers
      (n = 5) compared with superovulated heifers (n = 5). This was reflected in the
      number of differentially expressed genes (DEGs) identified between the two groups
      with 795 up- and 440 downregulated in superovulated endometria. Ten times more
      genes were altered by superovulation (n = 1,234) compared with the number altered
      due to elevated P4 within physiological ranges by insertion of a P4-releasing
      intravaginal device (n = 124) with only 22 DEGs common to both models of P4
      manipulation. Fewer genes were affected by superovulation in the embryo compared
      with the endometrium, (443 vs. 1,234 DEGs, respectively), and the manner in which
      genes were altered was different with 64.5% of genes up- and 35.5% of genes
      downregulated in the endometrium, compared with the 98.9% of DEGs upregulated in
      the embryo. In conclusion, superovulation induces significant changes in the
      transcriptome of the endometrium which are distinct from those in the embryo.

PMID- 23012395
TI  - Mitochondrial function, fatty acid metabolism, and immune system are relevant
      features of pig adipose tissue development.
AB  - The molecular mechanisms underlying the genetic control of fat development in
      humans and livestock species still require characterization. To gain insights on
      gene expression patterns associated with genetic propensity for adiposity, we
      compared subcutaneous adipose tissue (SCAT) transcriptomics profiles from two
      contrasted pig breeds for body fatness. Samples were obtained from Large White
      (LW; lean phenotype) and Basque pigs (B; low growth and high fat content) at 35
      kg (n = 5 per breed) or 145 kg body weight (n = 10 per breed). Using a custom
      adipose tissue microarray, we found 271 genes to be differentially expressed
      between the two breeds at both stages, out of which 123 were highly expressed in
      LW pigs and 148 genes were highly expressed in B pigs. Functional enrichment
      analysis based on gene ontology (GO) terms highlighted gene groups corresponding
      to the mitochondrial energy metabolism in LW pigs, whereas immune response was
      found significantly enriched in B pigs. Genes associated with lipid metabolism,
      such as ELOVL6, a gene involved in fatty acid elongation, had a lower expression
      in B compared with LW pigs. Furthermore, despite enlarged adipocyte diameters and
      higher plasma leptin concentration, B pigs displayed reduced lipogenic enzyme
      activities compared with LW pigs at 145 kg. Altogether, our results suggest that
      the development of adiposity was associated with a progressive worsening of the
      metabolic status, leading to a low-grade inflammatory state, and may thus be of
      significant interest for both livestock production and human health.

PMID- 23012396
TI  - Effects of perilipin 2 antisense oligonucleotide treatment on hepatic lipid
      metabolism and gene expression.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease
      worldwide. We previously showed that Perilipin 2 (Plin2), a member of lipid
      droplet protein family, is markedly increased in fatty liver, and its reduction
      in the liver of diet-induced obese mice by antisense oligonucleotide (ASO)
      decreased steatosis and enhanced insulin sensitivity. Plin2-ASO treatment
      markedly suppressed lipogenic gene expression. To gain a better understanding of
      the biological role of Plin2 in liver, we performed microarray analysis to
      determine genes differentially regulated by Plin2-ASO compared with a control
      (scrambled) oligonucleotide (Cont). Male C57BL/6J mice on a high-fat diet were
      treated with Plin2- or Cont-ASO for 4 wk. Plin2-ASO decreased hepatic
      triglycerides, and this was associated with changes in expression of 1,363 genes.
      We analyzed the data for functional clustering and validated the expression of
      representative genes using real-time PCR. On the high-fat diet, Plin2-ASO
      decreased the expression of enzymes involved in fatty acid metabolism (acsl1,
      lipe) and steroid metabolism (hmgcr, hsd3b5, hsd17b2), suggesting that Plin2
      affects hepatic lipid metabolism at the transcriptional level. Plin2-ASO also
      increased the expression of genes involved in regulation of hepatocyte
      proliferation (afp, H19), mitosis (ccna2, incenp, sgol1), and extracellular
      matrix (col1a1, col3a1, mmp8). Plin2-ASO had similar effects on gene expression
      in chow-fed mice. Together, these results indicate that Plin2 has diverse
      metabolic and structural roles in the liver, and its downregulation promotes
      hepatic fibrosis and proliferation.

PMID- 23012397
TI  - Gastrointestinal cancers reactive for the PAb416 antibody against JCV/SV40 T-Ag
      lack JCV DNA sequences while showing a distinctive pathologic profile.
AB  - AIM: Immunohistochemical and molecular studies have suggested an oncogenic role
      for JCV in gastrointestinal carcinomas, but at least in colorectal cancers, the
      data are far from being unambiguous. METHODS: Two large series of formalin-fixed
      paraffin-embedded gastric and colorectal cancers were analysed for the expression
      of JCV large T Antigen (T-Ag) with a panel of five antibodies, and for the
      presence of T-Ag DNA sequences using two PCR systems. RESULTS: Intense nuclear
      staining was observed in 54/116 (46%) colorectal, and in 92/234 (39%) gastric
      cancers, using the PAb416 monoclonal antibody against large T-Ag. In colorectal
      cancers, PAb416-positivity was directly related to the presence of chromosomal
      instability, lymph node metastases and a more advanced tumour stage, and
      inversely related to proximal tumour site and the presence of microsatellite
      instability (MSI). In gastric cancers, the glandular histotype, the presence of
      lymph node metastases, a low frequency of MSI and EBV infection, and a worse
      prognosis were significantly associated with PAb416 immunoreactivity. Moreover,
      at both these sites, PAb416 expression was significantly associated with p53
      nuclear accumulation. No positivity was obtained with all the other four anti-T
      Ag-antibodies, and molecular analysis failed to demonstrate the presence of JCV
      DNA sequences in tested cases. CONCLUSIONS: Our immunohistochemical and molecular
      results do not support the idea that JCV T-Ag has a role in gastrointestinal
      carcinogenesis. It is possible that PAb416, besides binding the viral protein,
      may cross-react with a hitherto undefined protein whose expression is associated
      with a distinct pathological profile and, at least in gastric cancers, with worse
      prognosis.

PMID- 23012398
TI  - Iron homeostasis in porphyria cutanea tarda: mutation analysis of promoter
      regions of CP, CYBRD1, HAMP and SLC40A1.

PMID- 23012399
TI  - Oral health as a risk factor for mortality in middle-aged men: the role of
      socioeconomic position and health behaviours.
AB  - BACKGROUND: There is evidence of an association between poor oral health and
      mortality. This association is usually attributed to inflammatory and nutrition
      pathways. However, the role of health behaviours and socioeconomic position has
      not been adequately examined. The aims of this study were to examine the
      association between oral health and premature death among middle-aged men and to
      test whether it was explained by socioeconomic position and behaviours. METHODS:
      Data were from the Vietnam Experience Study, a prospective cohort study of
      Vietnam War-era (1965-1971), American male army personnel. The authors examined
      risk of cause-specific and all-cause mortality in relation to poor oral health in
      middle age, adjusting for age, ethnicity, socioeconomic position, IQ, behavioural
      factors and systemic conditions. RESULTS: Men with poor oral health experienced a
      higher risk of cause-specific and all-cause mortality. HRs for all-cause
      mortality were 2.94 (95% CI 2.11 to 4.08) among individuals with poor oral health
      and 3.98 (95% CI 2.43 to 6.49) among edentates compared with those with good oral
      health after adjusting for ethnicity and age. The association attenuated but
      remained significant after further adjustment for systemic conditions,
      socioeconomic position and behaviours. Socioeconomic and behavioural factors
      explained 52% and 44% of mortality risks attributed to poor oral health and being
      edentate, respectively. CONCLUSION: The findings suggest that oral health
      mortality relation is partly due to measured covariates in the present study.
      Oral health appears to be a marker of socioeconomic and behavioural risk factors
      related to all-cause mortality.

PMID- 23012400
TI  - Using 'amenable mortality' as indicator of healthcare effectiveness in
      international comparisons: results of a validation study.
AB  - BACKGROUND AND STUDY AIMS: There is widespread consensus on the need for better
      indicators of the effectiveness of healthcare. We carried out an analysis of the
      validity of amenable mortality as an indicator of the effectiveness of
      healthcare, focusing on the potential use in routine surveillance systems of
      between-country variations in rates of mortality. We assessed whether the
      introduction of specific healthcare innovations coincided with declines in
      mortality from potentially amenable causes in seven European countries. In this
      paper, we summarise the main results of this study and illustrate them for four
      conditions. DATA AND METHODS: We identified 14 conditions for which considerable
      declines in mortality have been observed and for which there is reasonable
      evidence in the literature of the effectiveness of healthcare interventions to
      lower mortality. We determined the time at which these interventions were
      introduced and assessed whether the innovations coincided with favourable changes
      in the mortality trends from these conditions, measured using Poisson linear
      spline regression. All the evidence was then presented to a Delphi panel. MAIN
      RESULTS: The timing of innovation and favourable change in mortality trends
      coincided for only a few conditions. Other reasons for mortality decline are
      likely to include diffusion and improved quality of interventions and in
      incidence of diseases and their risk factors, but there is insufficient evidence
      to differentiate these at present. For most conditions, a Delphi panel could not
      reach consensus on the role of current mortality levels as measures of
      effectiveness of healthcare. DISCUSSION AND CONCLUSIONS: Improvements in
      healthcare probably lowered mortality from many of the conditions that we studied
      but occurred in a much more diffuse way than we assumed in the study design.
      Quantification of the contribution of healthcare to mortality requires adequate
      data on timing of innovation and trends in diffusion and quality and in incidence
      of disease, none of which are currently available. Given these gaps in knowledge,
      between-country differences in levels of mortality from amenable conditions
      should not be used for routine surveillance of healthcare performance. The timing
      and pace of mortality decline from amenable conditions may provide better
      indicators of healthcare performance.

PMID- 23012401
TI  - CD24 expression is important in male urothelial tumorigenesis and metastasis in
      mice and is androgen regulated.
AB  - Overexpression of CD24, a glycosyl phosphatidylinositol-linked sialoglycoprotein,
      is associated with poor outcome in urothelial carcinoma and contributes to
      experimental tumor growth and metastasis. However, the requirement for CD24
      (Cd24a in mice) in tumorigenesis and spontaneous metastasis from the orthotopic
      site remains uncharacterized. Using N-butyl-N-(4-hydroxybutyl) nitrosamine
      induction of invasive and metastatic bladder cancer, we show that Cd24a-deficient
      male mice developed fewer bladder tumors than C57BL/6 control male mice.
      Evaluating only mice with evidence of primary tumors, we observed that Cd24a
      deficient male mice also had fewer metastases than wild-type counterparts. In
      parallel observations, stratification of patients based on CD24
      immunohistochemical expression in their tumors revealed that high levels of CD24
      are associated with poor prognosis in males. In female patients and mice the
      above observations were not present. Given the significant role of CD24 in males,
      we sought to assess the relationship between androgen and CD24 regulation. We
      discovered that androgen receptor knockdown in UM-UC-3 and TCCSUP human
      urothelial carcinoma cell lines resulted in suppression of CD24 expression and
      cell proliferation. Androgen treatment also led to increased CD24 promoter
      activity, dependent on the presence of androgen receptor. In vivo, androgen
      deprivation resulted in reduced growth and CD24 expression of UM-UC-3 xenografts,
      and the latter was rescued by exogenous CD24 overexpression. These findings
      demonstrate an important role for CD24 in urothelial tumorigenesis and metastasis
      in male mice and indicate that CD24 is androgen regulated, providing the
      foundation for urothelial bladder cancer therapy with antiandrogens.

PMID- 23012403
TI  - Combinatorics of distance-based tree inference.
AB  - Several popular methods for phylogenetic inference (or hierarchical clustering)
      are based on a matrix of pairwise distances between taxa (or any kind of
      objects): The objective is to construct a tree with branch lengths so that the
      distances between the leaves in that tree are as close as possible to the input
      distances. If we hold the structure (topology) of the tree fixed, in some
      relevant cases (e.g., ordinary least squares) the optimal values for the branch
      lengths can be expressed using simple combinatorial formulae. Here we define a
      general form for these formulae and show that they all have two desirable
      properties: First, the common tree reconstruction approaches (least squares,
      minimum evolution), when used in combination with these formulae, are guaranteed
      to infer the correct tree when given enough data (consistency); second, the
      branch lengths of all the simple (nearest neighbor interchange) rearrangements of
      a tree can be calculated, optimally, in quadratic time in the size of the tree,
      thus allowing the efficient application of hill climbing heuristics. The study
      presented here is a continuation of that by Mihaescu and Pachter on branch length
      estimation [Mihaescu R, Pachter L (2008) Proc Natl Acad Sci USA 105:13206-13211].
      The focus here is on the inference of the tree itself and on providing a basis
      for novel algorithms to reconstruct trees from distances.

PMID- 23012402
TI  - Prolonged myelination in human neocortical evolution.
AB  - Nerve myelination facilitates saltatory action potential conduction and exhibits
      spatiotemporal variation during development associated with the acquisition of
      behavioral and cognitive maturity. Although human cognitive development is
      unique, it is not known whether the ontogenetic progression of myelination in the
      human neocortex is evolutionarily exceptional. In this study, we quantified
      myelinated axon fiber length density and the expression of myelin-related
      proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor
      (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of
      chimpanzees (N = 20) and humans (N = 33). Our examination revealed that
      neocortical myelination is developmentally protracted in humans compared with
      chimpanzees. In chimpanzees, the density of myelinated axons increased steadily
      until adult-like levels were achieved at approximately the time of sexual
      maturity. In contrast, humans displayed slower myelination during childhood,
      characterized by a delayed period of maturation that extended beyond late
      adolescence. This comparative research contributes evidence crucial to
      understanding the evolution of human cognition and behavior, which arises from
      the unfolding of nervous system development within the context of an enriched
      cultural environment. Perturbations of normal developmental processes and the
      decreased expression of myelin-related molecules have been related to psychiatric
      disorders such as schizophrenia. Thus, these species differences suggest that the
      human-specific shift in the timing of cortical maturation during adolescence may
      have implications for vulnerability to certain psychiatric disorders.

PMID- 23012404
TI  - Mammalian transcription factor A is a core component of the mitochondrial
      transcription machinery.
AB  - Transcription factor A (TFAM) functions as a DNA packaging factor in mammalian
      mitochondria. TFAM also binds sequence-specifically to sites immediately upstream
      of mitochondrial promoters, but there are conflicting data regarding its role as
      a core component of the mitochondrial transcription machinery. We here
      demonstrate that TFAM is required for transcription in mitochondrial extracts as
      well as in a reconstituted in vitro transcription system. The absolute
      requirement of TFAM can be relaxed by conditions that allow DNA breathing, i.e.,
      low salt concentrations or negatively supercoiled DNA templates. The situation is
      thus very similar to that described in nuclear RNA polymerase II-dependent
      transcription, in which the free energy of supercoiling can circumvent the need
      for a subset of basal transcription factors at specific promoters. In agreement
      with these observations, we demonstrate that TFAM has the capacity to induce
      negative supercoils in DNA, and, using the recently developed nucleobase analog
      FRET-pair tC(O)-tC(nitro), we find that TFAM distorts significantly the DNA
      structure. Our findings differ from recent observations reporting that TFAM is
      not a core component of the mitochondrial transcription machinery. Instead, our
      findings support a model in which TFAM is absolutely required to recruit the
      transcription machinery during initiation of transcription.

PMID- 23012405
TI  - Sequence-dependent sliding kinetics of p53.
AB  - Proper timing of gene expression requires that transcription factors (TFs)
      efficiently locate and bind their target sites within a genome. Theoretical
      studies have long proposed that one-dimensional sliding along DNA while
      simultaneously reading its sequence can accelerate TF's location of target sites.
      Sliding by prokaryotic and eukaryotic TFs were subsequently observed. More recent
      theoretical investigations have argued that simultaneous reading and sliding is
      not possible for TFs without their possessing at least two DNA-binding modes. The
      tumor suppressor p53 has been shown to slide on DNA, and recent experiments have
      offered structural and single molecule support for a two-mode model for the
      protein. If the model is applicable to p53, then the requirement that TFs be able
      to read while sliding implies that noncognate sites will affect p53's mobility on
      DNA, which will thus be generally sequence-dependent. Here, we confirm this
      prediction with single-molecule microscopy measurements of p53's local
      diffusivity on noncognate DNA. We show how a two-mode model accurately predicts
      the variation in local diffusivity, while a single-mode model does not. We
      further determine that the best model of sequence-specific binding energy
      includes terms for "hemi-specific" binding, with one dimer of tetrameric p53
      binding specifically to a half-site and the other binding nonspecifically to
      noncognate DNA. Our work provides evidence that the recognition by p53 of its
      targets and the timing thereof can depend on its noncognate binding properties
      and its ability to change between multiple modes of binding, in addition to the
      much better-studied effects of cognate-site binding.

PMID- 23012406
TI  - Conformational state of the MscS mechanosensitive channel in solution revealed by
      pulsed electron-electron double resonance (PELDOR) spectroscopy.
AB  - The heptameric mechanosensitive channel of small conductance (MscS) provides a
      critical function in Escherichia coli where it opens in response to increased
      bilayer tension. Three approaches have defined different closed and open
      structures of the channel, resulting in mutually incompatible models of gating.
      We have attached spin labels to cysteine mutants on key secondary structural
      elements specifically chosen to discriminate between the competing models. The
      resulting pulsed electron-electron double resonance (PELDOR) spectra matched
      predicted distance distributions for the open crystal structure of MscS. The fit
      for the predictions by structural models of MscS derived by other techniques was
      not convincing. The assignment of MscS as open in detergent by PELDOR was
      unexpected but is supported by two crystal structures of spin-labeled MscS.
      PELDOR is therefore shown to be a powerful experimental tool to interrogate the
      conformation of transmembrane regions of integral membrane proteins.

PMID- 23012407
TI  - Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson
      Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, fatal,
      segmental premature aging syndrome caused by a mutation in LMNA that produces the
      farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes
      failure to thrive and accelerated atherosclerosis leading to early death.
      Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical
      studies. Twenty-five patients with HGPS received the farnesyltransferase
      inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined
      as a 50% increase over pretherapy in estimated annual rate of weight gain, or
      change from pretherapy weight loss to statistically significant on-study weight
      gain. Nine patients experienced a >=50% increase, six experienced a >=50%
      decrease, and 10 remained stable with respect to rate of weight gain. Secondary
      outcomes included decreases in arterial pulse wave velocity and carotid artery
      echodensity and increases in skeletal rigidity and sensorineural hearing within
      patient subgroups. All patients improved in one or more of these outcomes.
      Results from this clinical treatment trial for children with HGPS provide
      preliminary evidence that lonafarnib may improve vascular stiffness, bone
      structure, and audiological status.

PMID- 23012408
TI  - Therapeutic stem cells expressing variants of EGFR-specific nanobodies have
      antitumor effects.
AB  - The deregulation of the epidermal growth factor receptor (EGFR) has a significant
      role in the progression of tumors. Despite the development of a number of EGFR
      targeting agents that can arrest tumor growth, their success in the clinic is
      limited in several tumor types, particularly in the highly malignant glioblastoma
      multiforme (GBM). In this study, we generated and characterized EGFR-specific
      nanobodies (ENb) and imageable and proapoptotic ENb immunoconjugates released
      from stem cells (SC) to ultimately develop a unique EGFR-targeted therapy for
      GBM. We show that ENbs released from SCs specifically localize to tumors, inhibit
      EGFR signaling resulting in reduced GBM growth and invasiveness in vitro and in
      vivo in both established and primary GBM cell lines. We also show that ENb primes
      GBM cells for proapoptotic tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL)-induced apoptosis. Furthermore, SC-delivered immunoconjugates of
      ENb and TRAIL target a wide spectrum of GBM cell types with varying degrees of
      TRAIL resistance and significantly reduce GBM growth and invasion in both
      established and primary invasive GBM in mice. This study demonstrates the
      efficacy of SC-based EGFR targeted therapy in GBMs and provides a unique approach
      with clinical implications.

PMID- 23012409
TI  - Massively parallel measurements of molecular interaction kinetics on a
      microfluidic platform.
AB  - Quantitative biology requires quantitative data. No high-throughput technologies
      exist capable of obtaining several hundred independent kinetic binding
      measurements in a single experiment. We present an integrated microfluidic device
      (k-MITOMI) for the simultaneous kinetic characterization of 768 biomolecular
      interactions. We applied k-MITOMI to the kinetic analysis of transcription factor
      (TF)-DNA interactions, measuring the detailed kinetic landscapes of the mouse TF
      Zif268, and the yeast TFs Tye7p, Yox1p, and Tbf1p. We demonstrated the integrated
      nature of k-MITOMI by expressing, purifying, and characterizing 27 additional
      yeast transcription factors in parallel on a single device. Overall, we obtained
      2,388 association and dissociation curves of 223 unique molecular interactions
      with equilibrium dissociation constants ranging from 2 * 10(-6) M to 2 * 10(-9)
      M, and dissociation rate constants of approximately 6 s(-1) to 8.5 * 10(-3) s(
      1). Association rate constants were uniform across 3 TF families, ranging from
      3.7 * 10(6) M(-1) s(-1) to 9.6 * 10(7) M(-1) s(-1), and are well below the
      diffusion limit. We expect that k-MITOMI will contribute to our quantitative
      understanding of biological systems and accelerate the development and
      characterization of engineered systems.

PMID- 23012410
TI  - Frost halos from supercooled water droplets.
AB  - Water freezing on solid surfaces is ubiquitous in nature. Even though
      icing/frosting impairs the performance and safety in many processes, its
      mechanism remains inadequately understood. Changing atmospheric conditions,
      surface properties, the complexity of icing physics, and the unorthodox behavior
      of water are the primary factors that make icing and frost formation intriguing
      and difficult to predict. In addition to its unquestioned scientific and
      practical importance, unraveling the frosting mechanism under different
      conditions is a prerequisite to develop "icephobic" surfaces, which may avoid ice
      formation and contamination. In this work we demonstrate that evaporation from a
      freezing supercooled sessile droplet, which starts explosively due to the sudden
      latent heat released upon recalescent freezing, generates a condensation halo
      around the droplet, which crystallizes and drastically affects the surface
      behavior. The process involves simultaneous multiple phase transitions and may
      also spread icing by initiating sequential freezing of neighboring droplets in
      the form of a domino effect and frost propagation. Experiments under controlled
      humidity conditions using substrates differing up to three orders of magnitude in
      thermal conductivity establish that a delicate balance between heat diffusion and
      vapor transport determines the final expanse of the frozen condensate halo,
      which, in turn, controls frost formation and propagation.

PMID- 23012411
TI  - Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro
      and in vivo.
AB  - Nicastrin (NCT) is a crucial component of the gamma-secretase (GS) enzyme, which
      prompted investigations into its biological role in cancer. We have previously
      shown that nicastrin is overexpressed in breast cancer (BC), conferring worse
      overall survival in invasive, ERalpha negative patients. Here, we used 2D and 3D
      Matrigel, anchorage-independent growth conditions and a breast cancer xenograft
      mouse model to assess the impact of nicastrin on breast cancer stem cell (BCSC)
      propagation and invasion in vitro and tumor growth in vivo. Stable knockdown of
      nicastrin in HCC1806 breast cancer cells reduced cell invasion by 51.4 +/- 1.7%,
      accompanied by a morphological change to a rounded cell phenotype and down
      regulation of vimentin, Snail, Twist, MMP2, and MMP9. We observed a reduction of
      the pool of CD44(+)/CD24(-) and ALDH1 high breast cancer stem cells by threefold
      and twofold, respectively, and a reduction by 2.6-fold of the mammospheres
      formation. Nicastrin overexpression in nontransformed MCF10A cells caused an
      induction of epithelial to mesenchymal regulators, as well as a fivefold
      increased ALDH1 activity, a threefold enrichment for CD44(+)/CD24(-) stem cells,
      and a 3.2-fold enhanced mammosphere-forming capacity. Using the gamma-sescretase
      inhibiton, Notch1/4 siRNA, and Akt inhibition, we show that nicastrin regulates
      breast cancer stem cells partly through Notch1 and the Akt pathway. Exploiting
      serial dilution transplantation of the HCC1806 cells expressing nicastrin and
      HCC1806 stably depleted of nicastrin, in vivo, we demonstrate that nicastrin
      inhibition may be relevant for the reduced tumorigenicity of breast cancer cells.
      These data could serve as a benchmark for development of nicastrin-targeted
      therapies in breast cancer.

PMID- 23012412
TI  - Cannabinoid receptor 1-expressing neurons in the nucleus accumbens.
AB  - Endocannabinoid signaling critically regulates emotional and motivational states
      via activation of cannabinoid receptor 1 (CB1) in the brain. The nucleus
      accumbens (NAc) functions to gate emotional and motivational responses. Although
      expression of CB1 in the NAc is low, manipulation of CB1 signaling within the NAc
      triggers robust emotional/motivational alterations related to drug addiction and
      other psychiatric disorders, and these effects cannot be exclusively attributed
      to CB1 located at afferents to the NAc. Rather, CB1-expressing neurons in the
      NAc, although sparse, appear to be critical for emotional and motivational
      responses. However, the cellular properties of these neurons remain largely
      unknown. Here, we generated a knock-in mouse line in which CB1-expressing neurons
      expressed the fluorescent protein td-Tomato (tdT). Using these mice, we
      demonstrated that tdT-positive neurons within the NAc were exclusively fast
      spiking interneurons (FSIs). These FSIs were electrically coupled with each
      other, and thus may help synchronize populations/ensembles of NAc neurons. CB1
      expressing FSIs also form GABAergic synapses on adjacent medium spiny neurons
      (MSNs), providing feed-forward inhibition of NAc output. Furthermore, the
      membrane excitability of tdT-positive FSIs in the NAc was up-regulated after
      withdrawal from cocaine exposure, an effect that might increase FSI-to-MSN
      inhibition. Taken together with our previous findings that the membrane
      excitability of NAc MSNs is decreased during cocaine withdrawal, the present
      findings suggest that the basal functional output of the NAc is inhibited during
      cocaine withdrawal by multiple mechanisms. As such, CB1-expressing FSIs are
      targeted by cocaine exposure to influence the overall functional output of the
      NAc.

PMID- 23012413
TI  - Overexpressing mouse model demonstrates the protective role of Muc5ac in the
      lungs.
AB  - MUC5AC, a major gel-forming mucin expressed in the lungs, is secreted at
      increased rates in response to infectious agents, implying that mucins exert a
      protective role against inhaled pathogens. However, epidemiological and
      pathological studies suggest that excessive mucin secretion causes airways
      obstruction and inflammation. To determine whether increased MUC5AC secretion
      alone produces airway obstruction and/or inflammation, we generated a mouse model
      overexpressing Muc5ac mRNA ~20-fold in the lungs, using the rCCSP promoter. The
      Muc5ac cDNA was cloned from mouse lungs and tagged internally with GFP.
      Bronchoalveolar lavage fluid (BALF) analysis demonstrated an approximate 18-fold
      increase in Muc5ac protein, which formed high-molecular-weight polymers.
      Histopathological studies and cell counts revealed no airway mucus obstruction or
      inflammation in the lungs of Muc5ac-transgenic (Muc5ac-Tg) mice. Mucus clearance
      was preserved, implying that the excess Muc5ac secretion produced an "expanded"
      rather than more concentrated mucus layer, a prediction confirmed by electron
      microscopy. To test whether the larger mucus barrier conferred increased
      protection against pathogens, Muc5ac-Tg animals were challenged with PR8/H1N1
      influenza viruses and showed significant decreases in infection and neutrophilic
      responses. Plaque assay experiments demonstrated that Muc5ac-Tg BALF and purified
      Muc5ac reduced infection, likely via binding to alpha2,3-linked sialic acids,
      consistent with influenza protection in vivo. In conclusion, the normal mucus
      transport and absence of a pulmonary phenotype in Muc5ac-Tg mice suggests that
      mucin hypersecretion alone is not sufficient to trigger luminal mucus plugging or
      airways inflammation/goblet cell hyperplasia. In contrast, increased Muc5ac
      secretion appears to exhibit a protective role against influenza infection.

PMID- 23012414
TI  - Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is
      mediated by astrocytes.
AB  - Although cholinergic innervation of the cortex by the nucleus basalis (NB) is
      known to modulate cortical neuronal responses and instruct cortical plasticity,
      little is known about the underlying cellular mechanisms. Using cell-attached
      recordings in vivo, we demonstrate that electrical stimulation of the NB, paired
      with visual stimulation, can induce significant potentiation of visual responses
      in excitatory neurons of the primary visual cortex in mice. We further show with
      in vivo two-photon calcium imaging, ex vivo calcium imaging, and whole-cell
      recordings that this pairing-induced potentiation is mediated by direct
      cholinergic activation of primary visual cortex astrocytes via muscarinic AChRs.
      The potentiation is absent in conditional inositol 1,4,5 trisphosphate receptor
      type 2 KO mice, which lack astrocyte calcium activation, and is stimulus
      specific, because pairing NB stimulation with a specific visual orientation
      reveals a highly selective potentiation of responses to the paired orientation
      compared with unpaired orientations. Collectively, these findings reveal a unique
      and surprising role for astrocytes in NB-induced stimulus-specific plasticity in
      the cerebral cortex.

PMID- 23012415
TI  - Hydra meiosis reveals unexpected conservation of structural synaptonemal complex
      proteins across metazoans.
AB  - The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable
      pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable
      tripartite structure is evolutionarily well conserved and can be found in almost
      all sexually reproducing organisms. However, comparison of the different SC
      protein components in the common meiosis model organisms Saccharomyces
      cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila
      melanogaster, and Mus musculus revealed no sequence homology. This discrepancy
      challenged the hypothesis that the SC arose only once in evolution. To pursue
      this matter we focused on the evolution of SYCP1 and SYCP3, the two major
      structural SC proteins of mammals. Remarkably, our comparative bioinformatic and
      expression studies revealed that SYCP1 and SYCP3 are also components of the SC in
      the basal metazoan Hydra. In contrast to previous assumptions, we therefore
      conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins
      across metazoans.

PMID- 23012416
TI  - Leadership is associated with lower levels of stress.
AB  - As leaders ascend to more powerful positions in their groups, they face ever
      increasing demands. As a result, there is a common perception that leaders have
      higher stress levels than nonleaders. However, if leaders also experience a
      heightened sense of control--a psychological factor known to have powerful stress
      buffering effects--leadership should be associated with reduced stress levels.
      Using unique samples of real leaders, including military officers and government
      officials, we found that, compared with nonleaders, leaders had lower levels of
      the stress hormone cortisol and lower reports of anxiety (study 1). In study 2,
      leaders holding more powerful positions exhibited lower cortisol levels and less
      anxiety than leaders holding less powerful positions, a relationship explained
      significantly by their greater sense of control. Altogether, these findings
      reveal a clear relationship between leadership and stress, with leadership level
      being inversely related to stress.

PMID- 23012417
TI  - Predicting errors from reconfiguration patterns in human brain networks.
AB  - Task preparation is a complex cognitive process that implements anticipatory
      adjustments to facilitate future task performance. Little is known about
      quantitative network parameters governing this process in humans. Using
      functional magnetic resonance imaging (fMRI) and functional connectivity
      measurements, we show that the large-scale topology of the brain network involved
      in task preparation shows a pattern of dynamic reconfigurations that guides
      optimal behavior. This network could be decomposed into two distinct topological
      structures, an error-resilient core acting as a major hub that integrates most of
      the network's communication and a predominantly sensory periphery showing more
      flexible network adaptations. During task preparation, core-periphery
      interactions were dynamically adjusted. Task-relevant visual areas showed a
      higher topological proximity to the network core and an enhancement in their
      local centrality and interconnectivity. Failure to reconfigure the network
      topology was predictive for errors, indicating that anticipatory network
      reconfigurations are crucial for successful task performance. On the basis of a
      unique network decoding approach, we also develop a general framework for the
      identification of characteristic patterns in complex networks, which is
      applicable to other fields in neuroscience that relate dynamic network properties
      to behavior.

PMID- 23012418
TI  - From simple innate biases to complex visual concepts.
AB  - Early in development, infants learn to solve visual problems that are highly
      challenging for current computational methods. We present a model that deals with
      two fundamental problems in which the gap between computational difficulty and
      infant learning is particularly striking: learning to recognize hands and
      learning to recognize gaze direction. The model is shown a stream of natural
      videos and learns without any supervision to detect human hands by appearance and
      by context, as well as direction of gaze, in complex natural scenes. The
      algorithm is guided by an empirically motivated innate mechanism--the detection
      of "mover" events in dynamic images, which are the events of a moving image
      region causing a stationary region to move or change after contact. Mover events
      provide an internal teaching signal, which is shown to be more effective than
      alternative cues and sufficient for the efficient acquisition of hand and gaze
      representations. The implications go beyond the specific tasks, by showing how
      domain-specific "proto concepts" can guide the system to acquire meaningful
      concepts, which are significant to the observer but statistically inconspicuous
      in the sensory input.

PMID- 23012419
TI  - Single nucleotide in the MTF-1 binding site can determine metal-specific
      transcription activation.
AB  - Cells respond to changes in environment by shifting their gene expression profile
      to deal with the new conditions. The cellular response to changes in metal
      homeostasis is an important example of this. Transition metals such as iron,
      zinc, and copper are essential micronutrients but other metals such as cadmium
      are simply toxic. The cell must maintain metal concentrations in a window that
      supports efficient metabolic function but must also protect against the damaging
      effects of high concentrations of these metals. One way a cell regulates metal
      homeostasis is to control genes involved in metal mobilization and storage. Much
      of this regulation occurs at the level of transcription and the protein most
      responsible for this is the conserved metal responsive transcription factor 1
      (MTF-1). Interestingly, the nature of the changes in the gene expression profile
      depends on the type of exposure. The cell somehow senses the kind of the metal
      challenge and responds appropriately. We have been using the Drosophila system to
      try to understand the mechanism of this metal discrimination. Using genome-wide
      mapping of MTF-1 binding under different metal stresses we find that,
      surprisingly, MTF-1 chooses different DNA binding sites depending on the specific
      nature of the metal insult. We also find that the type of binding site chosen is
      an important component of the capability to induce the metal-specific
      transcription activation.

PMID- 23012420
TI  - The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing.
AB  - Phagocytosis is a primary defense program orchestrated by monocytes/macrophages.
      Unregulated phagocytosis can lead to pathological conditions. In the current
      study we have demonstrated that Wnt5a stimulates phagocytosis through PI3 kinase
      Rac1 and lipid-raft-dependent processes. Wnt5a-mediated augmentation in
      phagocytosis is suppressed by blocking expression of the putative Wnt5a receptor
      Frizzled 5. Enhanced phagocytosis of bacteria by Wnt5a-Fz5 signaling increases
      the secretion of proinflammatory cytokines, but not the bacterial killing rate.
      Furthermore, a small molecule inhibitor of Wnt production, IWP-2, which reduces
      secretion of functionally active Wnt5a, not only suppresses both phagocytosis and
      the secretion of proinflammatory cytokines but also accelerates the bacterial
      killing rate.

PMID- 23012421
TI  - Dispersion by Pseudomonas aeruginosa requires an unusual posttranslational
      modification of BdlA.
AB  - Dispersion enables biofilm bacteria to transit from the biofilm to the planktonic
      growth state and to spawn novel communities in new locales. Although the
      chemotaxis protein BdlA plays a role in the dispersion of Pseudomonas aeruginosa
      biofilms in response to environmental cues, little is known about regulation of
      BdlA activity or how BdlA modulates the dispersion response. Here, we demonstrate
      that BdlA in its native form is inactive and is activated upon nonprocessive
      proteolysis at a ClpP-protease-like cleavage site located between the Per Arnt
      Sim (PAS) sensory domains PASa and PASb. Activation of BdlA to enable biofilm
      dispersion requires phosphorylation at tyrosine-238 as a signal, elevated c-di
      GMP levels, the chaperone ClpD, and the protease ClpP. The resulting truncated
      BdlA polypeptide chains directly interact and are required for P. aeruginosa
      biofilms to disperse. Our results provide a basis for understanding the mechanism
      of biofilm dispersion that may be applicable to a large number of biofilm-forming
      pathogenic species. Insights into the mechanism of BdlA function have
      implications for the control of biofilm-related infections.

PMID- 23012422
TI  - Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of
      the rhesus monkey.
AB  - Widespread use of the endocrine disrupting chemical bisphenol A (BPA) in consumer
      products has resulted in nearly continuous human exposure. In rodents, low-dose
      exposures have been reported to adversely affect two distinct stages of oogenesis
      in the developing ovary: the events of prophase at the onset of meiosis in the
      fetal ovary and the formation of follicles in the perinatal ovary. Because these
      effects could influence the reproductive longevity and success of the exposed
      individual, we conducted studies in the rhesus monkey to determine whether BPA
      induces similar disturbances in the developing primate ovary. The routes and
      levels of human exposure are unclear; hence, two different exposure protocols
      were used: single daily oral doses and continuous exposure via subdermal implant.
      Our analyses of second trimester fetuses exposed at the time of meiotic onset
      suggest that, as in mice, BPA induces subtle disturbances in the prophase events
      that set the stage for chromosome segregation at the first meiotic division. Our
      analyses of third-trimester fetuses exposed to single daily oral doses during the
      time of follicle formation revealed an increase in multioocyte follicles
      analogous to that reported in rodents. However, two unique phenotypes were
      evident in continuously exposed animals: persistent unenclosed oocytes in the
      medullary region and small, nongrowing oocytes in secondary and antral follicles.
      Because effects on both stages of oogenesis were elicited using doses that yield
      circulating levels of BPA analogous to those reported in humans, these findings
      raise concerns for human reproductive health.

PMID- 23012423
TI  - MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small
      cell lung cancer through BIM down-regulation.
AB  - MicroRNAs (miRNAs) have an important role in the development of chemosensitivity
      or chemoresistance in different types of cancer. Activation of the ERK1/2 pathway
      is a major determinant of diverse cellular processes and cancer development and
      is responsible for the transcription of several important miRNAs. Here we show a
      link between the ERK1/2 pathway and BIM expression through miR-494. We blocked
      ERK1/2 nuclear activity through the overexpression of an ERK1/2 natural
      interactor, the protein PED/PEA15, and we performed a microRNA expression
      profile. miR-494 was the most down-regulated microRNA after ERK1/2 inactivation.
      Moreover, we found that miR-494 induced Tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL) resistance in non-small-cell lung cancer
      (NSCLC) through the down-modulation of BIM. Elucidation of this undiscovered
      ERK1/2 pathway that regulates apoptosis and cell proliferation through miR-494 in
      NSCLC will greatly enhance our understanding of the mechanisms responsible for
      TRAIL resistance and will provide an additional arm for the development of
      anticancer therapies.

PMID- 23012424
TI  - SAM-pointed domain ETS factor mediates epithelial cell-intrinsic innate immune
      signaling during airway mucous metaplasia.
AB  - Airway mucus plays a critical role in clearing inhaled toxins, particles, and
      pathogens. Diverse toxic, inflammatory, and infectious insults induce airway
      mucus secretion and goblet cell metaplasia to preserve airway sterility and
      homeostasis. However, goblet cell metaplasia, mucus hypersecretion, and airway
      obstruction are integral features of inflammatory lung diseases, including
      asthma, chronic obstructive lung disease, and cystic fibrosis, which cause an
      immense burden of morbidity and mortality. These chronic lung diseases are united
      by susceptibility to microbial colonization and recurrent airway infections.
      Whether these twinned phenomena (mucous metaplasia, compromised host defenses)
      are causally related has been unclear. Here, we demonstrate that SAM pointed
      domain ETS factor (SPDEF) was induced by rhinoviral infection of primary human
      airway cells and that cytoplasmic activities of SPDEF, a transcriptional
      regulator of airway goblet cell metaplasia, inhibited Toll-like receptor (TLR)
      activation of epithelial cells. SPDEF bound to and inhibited activities of TLR
      signaling adapters, MyD88 and TRIF, inhibiting MyD88-induced cytokine production
      and TRIF-induced interferon beta production. Conditional expression of SPDEF in
      airway epithelial cells in vivo inhibited LPS-induced neutrophilic infiltration
      and bacterial clearance. SPDEF-mediated inhibition of both TLR and type I
      interferon signaling likely protects the lung against inflammatory damage when
      inciting stimuli are not eradicated. Present findings provide, at least in part,
      a molecular explanation for increased susceptibility to infection in lung
      diseases associated with mucous metaplasia and a mechanism by which patients with
      florid mucous metaplasia may tolerate microbial burdens that are usually
      associated with fulminant inflammatory disease in normal hosts.

PMID- 23012425
TI  - Spatiotemporally controlled single cell sonoporation.
AB  - This paper presents unique approaches to enable control and quantification of
      ultrasound-mediated cell membrane disruption, or sonoporation, at the single-cell
      level. Ultrasound excitation of microbubbles that were targeted to the plasma
      membrane of HEK-293 cells generated spatially and temporally controlled membrane
      disruption with high repeatability. Using whole-cell patch clamp recording
      combined with fluorescence microscopy, we obtained time-resolved measurements of
      single-cell sonoporation and quantified the size and resealing rate of pores. We
      measured the intracellular diffusion coefficient of cytoplasmic RNA/DNA from
      sonoporation-induced transport of an intercalating fluorescent dye into and
      within single cells. We achieved spatiotemporally controlled delivery with
      subcellular precision and calcium signaling in targeted cells by selective
      excitation of microbubbles. Finally, we utilized sonoporation to deliver calcein,
      a membrane-impermeant substrate of multidrug resistance protein-1 (MRP1), into
      HEK-MRP1 cells, which overexpress MRP1, and monitored the calcein efflux by MRP1.
      This approach made it possible to measure the efflux rate in individual cells and
      to compare it directly to the efflux rate in parental control cells that do not
      express MRP1.

PMID- 23012426
TI  - Functionalized multiwalled carbon nanotubes as ultrasound contrast agents.
AB  - Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical
      practice. Here, we are unique in describing the use of functionalized multiwalled
      carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential
      application as ultrasound contrast agents. Initially, we carried out a thorough
      investigation to assess the echogenic property of the nanotubes in vitro. We
      demonstrated their long-lasting ultrasound contrast properties. We also showed
      that ultrasound signal of functionalized MWCNTs is higher than graphene oxide,
      pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the
      ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a
      commercially available contrast agent. Then, we found that MWCNTs were highly
      echogenic in liver and heart through ex vivo experiments using pig as an animal
      model. In contrast to the majority of ultrasound contrast agents, we observed in
      a phantom bladder that the tubes can be visualized within a wide variety of
      frequencies (i.e., 5.5-10 MHz) and 12.5 MHz using tissue harmonic imaging
      modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be
      observed at low frequencies, which are appropriate for abdominal organs.
      Importantly, we did not report any toxicity of CNTs after 7 d from the injection
      by animal autopsy, organ histology and immunostaining, blood count, and chemical
      profile. Our results reveal the enormous potential of CNTs as ultrasound contrast
      agents, giving support for their future applications as theranostic
      nanoparticles, combining diagnostic and therapeutic modalities.

PMID- 23012427
TI  - NMDA receptor function in large-scale anticorrelated neural systems with
      implications for cognition and schizophrenia.
AB  - Glutamatergic neurotransmission mediated by N-methyl-d-aspartate (NMDA) receptors
      is vital for the cortical computations underlying cognition and might be
      disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on
      this topic have been limited to processes in local circuits; however, cognition
      involves large-scale brain systems with multiple interacting regions. A prominent
      feature of the human brain's global architecture is the anticorrelation of
      default-mode vs. task-positive systems. Here, we show that administration of an
      NMDA glutamate receptor antagonist, ketamine, disrupted the reciprocal
      relationship between these systems in terms of task-dependent activation and
      connectivity during performance of delayed working memory. Furthermore, the
      degree of this disruption predicted task performance and transiently evoked
      symptoms characteristic of schizophrenia. We offer a parsimonious hypothesis for
      this disruption via biophysically realistic computational modeling, namely
      cortical disinhibition. Together, the present findings establish links between
      glutamate's role in the organization of large-scale anticorrelated neural
      systems, cognition, and symptoms associated with schizophrenia in humans.

PMID- 23012428
TI  - Antiparallel coiled-coil-mediated dimerization of myosin X.
AB  - Processive movements of unconventional myosins on actin filaments generally
      require motor dimerization. A commonly accepted myosin dimerization mechanism is
      via formation of a parallel coiled-coil dimer by a stretch of amino acid residues
      immediately carboxyl-terminal to the motor's lever-arm domain. Here, we discover
      that the predicted coiled-coil region of myosin X forms a highly stable,
      antiparallel coiled-coil dimer (anti-CC). Disruption of the anti-CC either by
      single-point mutations or by replacement of the anti-CC with a parallel coiled
      coil with a similar length compromised the filopodial induction activity of
      myosin X. We further show that the anti-CC and the single alpha-helical domain of
      myosin X are connected by a semirigid helical linker. The anti-CC-mediated
      dimerization may enable myosin X to walk on both single and bundled actin
      filaments.

PMID- 23012430
TI  - Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in
      LPS-activated macrophages.
AB  - IL-10 is a key anti-inflammatory cytokine secreted by activated macrophages as a
      feedback control mechanism to prevent excessive inflammatory responses. Here, we
      define multiple intracellular trafficking pathways involved in the secretion of
      newly synthesized IL-10 from macrophages following TLR4 activation with LPS, and
      show how this relates to the previously defined trafficking pathways for IL-6 and
      TNF in macrophages simultaneously producing these proinflammatory cytokines. IL
      10 exits the Golgi in multiple tubular carriers, including those dependent on
      p230GRIP. Some of the IL-10 is then delivered to recycling endosomes, where
      cytokine sorting may occur prior to its release. Another portion of the IL-10 is
      delivered to the cell surface in distinct vesicles colabeled for apoE. Thus, we
      show at least two post-Golgi pathways via which IL-10 is trafficked, ensuring its
      secretion from activated macrophages under different physiological conditions.

PMID- 23012429
TI  - beta-Arrestin-2 mediates the proinflammatory effects of proteinase-activated
      receptor-2 in the airway.
AB  - Proteinase-Activated receptor-2 (PAR(2)), a G-protein-coupled Receptor, activated
      by serine proteinases, is reported to have both protective and proinflammatory
      effects in the airway. Given these opposing actions, both inhibitors and
      activators of PAR(2) have been proposed for treating asthma. PAR(2) can signal
      through two independent pathways: a beta-arrestin-dependent one that promotes
      leukocyte migration, and a G-protein/Ca(2+) one that is required for
      prostaglandin E(2) (PGE(2)) production and bronchiolar smooth muscle relaxation.
      We hypothesized that the proinflammatory responses to PAR(2) activation are
      mediated by beta-arrestins, whereas the protective effects are not. Using a mouse
      ovalbumin model for PAR(2)-modulated airway inflammation, we observed decreased
      leukocyte recruitment, cytokine production, and mucin production in beta-arrestin
      2(-/-) mice. In contrast, PAR(2)-mediated PGE(2) production, smooth muscle
      relaxation, and decreased baseline airway resistance (measures of putative PAR(2)
      "protective" effects) were independent of beta-arrestin-2. Flow cytometry and
      cytospins reveal that lung eosinophil and CD4 T-cell infiltration, and production
      of IL-4, IL-6, IL-13, and TNFalpha, were enhanced in wild-type but not beta
      arrestin-2(-/-) mice. Using the forced oscillation technique to measure airway
      resistance reveals that PAR(2) activation protects against airway
      hyperresponsiveness by an unknown mechanism, possibly involving smooth muscle
      relaxation. Our data suggest that the PAR(2)-enhanced inflammatory process is
      beta-arrestin-2 dependent, whereas the protective anticonstrictor effect of
      bronchial epithelial PAR(2) may be beta-arrestin independent.

PMID- 23012431
TI  - Reduced numbers of dendritic cells with a tolerogenic phenotype in the
      prediabetic pancreas of NOD mice.
AB  - The NOD mouse is a widely used animal model of autoimmune diabetes. Prior to the
      onset of lymphocytic insulitis, DCs accumulate at the islet edges. Our recent
      work indicated that these DCs may derive from aberrantly proliferating local
      precursor cells. As CD8alpha(+) DCs play a role in tolerance induction in steady
      state conditions, we hypothesized that the autoimmune phenotype might associate
      with deficiencies in CD8alpha(+) DCs in the prediabetic NOD mouse pancreas. We
      studied CD8alpha(+) DCs in the pancreas and pLNs of NOD and control mice,
      focusing on molecules associated with tolerance induction (CD103, Langerin,
      CLEC9A, CCR5). mRNA expression levels of tolerance-modulating cytokines were
      studied in pancreatic CD8alpha(+) DCs of NOD and control mice. In the NOD
      pancreas, the frequency of CD8alpha(+)CD103(+)Langerin(+) cells was reduced
      significantly compared with control mice. NOD pancreatic
      CD8alpha(+)CD103(+)Langerin(+) DCs expressed reduced levels of CCR5, CLEC9A, and
      IL-10 as compared with control DCs. These alterations in the
      CD8alpha(+)CD103(+)Langerin(+) DC population were not present in pLNs. We
      demonstrate local abnormalities in the CD8alpha(+) DC population in the
      prediabetic NOD pancreas. These data suggest that abnormal differentiation of
      pancreatic DCs contributes to loss of tolerance, hallmarking the development of
      autoimmune diabetes.

PMID- 23012432
TI  - The molecular mechanism of the UVR8 UV-B photoreceptor.

PMID- 23012433
TI  - In vivo function of tryptophans in the Arabidopsis UV-B photoreceptor UVR8.
AB  - Arabidopsis thaliana UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor specifically
      for UV-B light that initiates photomorphogenic responses in plants. UV-B exposure
      causes rapid conversion of UVR8 from dimer to monomer, accumulation in the
      nucleus, and interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), which
      functions with UVR8 in UV-B responses. Studies in yeast and with purified UVR8
      implicate several tryptophan amino acids in UV-B photoreception. However, their
      roles in UV-B responses in plants, and the functional significance of all 14 UVR8
      tryptophans, are not known. Here we report the functions of the UVR8 tryptophans
      in vivo. Three tryptophans in the beta-propeller core are important in
      maintaining structural stability and function of UVR8. However, mutation of three
      other core tryptophans and four at the dimeric interface has no apparent effect
      on function in vivo. Mutation of three tryptophans implicated in UV-B
      photoreception, W233, W285, and W337, impairs photomorphogenic responses to
      different extents. W285 is essential for UVR8 function in plants, whereas W233 is
      important but not essential for function, and W337 has a lesser role. Ala mutants
      of these tryptophans appear monomeric and constitutively bind COP1 in plants, but
      their responses indicate that monomer formation and COP1 binding are not
      sufficient for UVR8 function.

PMID- 23012435
TI  - Rapid centromere evolution in potato: invasion of the satellite repeats.

PMID- 23012434
TI  - YSL16 is a phloem-localized transporter of the copper-nicotianamine complex that
      is responsible for copper distribution in rice.
AB  - Cu is an essential element for plant growth, but the molecular mechanisms of its
      distribution and redistribution within the plants are unknown. Here, we report
      that Yellow stripe-like16 (YSL16) is involved in Cu distribution and
      redistribution in rice (Oryza sativa). Rice YSL16 was expressed in the roots,
      leaves, and unelongated nodes at the vegetative growth stage and highly expressed
      in the upper nodes at the reproductive stage. YSL16 was expressed at the phloem
      of nodes and vascular tissues of leaves. Knockout of this gene resulted in a
      higher Cu concentration in the older leaves but a lower concentration in the
      younger leaves at the vegetative stage. At the reproductive stage, a higher Cu
      concentration was found in the flag leaf and husk, but less Cu was present in the
      brown rice, resulting in a significant reduction in fertility in the knockout
      line. Isotope labeling experiments with (65)Cu showed that the mutant lost the
      ability to transport Cu-nicotianamine from older to younger leaves and from the
      flag leaf to the panicle. Rice YSL16 transported the Cu-nicotianamine complex in
      yeast. Taken together, our results indicate that Os-YSL16 is a Cu-nicotianamine
      transporter that is required for delivering Cu to the developing young tissues
      and seeds through phloem transport.

PMID- 23012436
TI  - Phospholipid:diacylglycerol acyltransferase is a multifunctional enzyme involved
      in membrane lipid turnover and degradation while synthesizing triacylglycerol in
      the unicellular green microalga Chlamydomonas reinhardtii.
AB  - Many unicellular microalgae produce large amounts (~20 to 50% of cell dry weight)
      of triacylglycerols (TAGs) under stress (e.g., nutrient starvation and high
      light), but the synthesis and physiological role of TAG are poorly understood. We
      present detailed genetic, biochemical, functional, and physiological analyses of
      phospholipid:diacylglycerol acyltransferase (PDAT) in the green microalga
      Chlamydomonas reinhardtii, which catalyzes TAG synthesis via two pathways:
      transacylation of diacylglycerol (DAG) with acyl groups from phospholipids and
      galactolipids and DAG:DAG transacylation. We demonstrate that PDAT also possesses
      acyl hydrolase activities using TAG, phospholipids, galactolipids, and
      cholesteryl esters as substrates. Artificial microRNA silencing of PDAT in C.
      reinhardtii alters the membrane lipid composition, reducing the maximum specific
      growth rate. The data suggest that PDAT-mediated membrane lipid turnover and TAG
      synthesis is essential for vigorous growth under favorable culture conditions and
      for membrane lipid degradation with concomitant production of TAG for survival
      under stress. The strong lipase activity of PDAT with broad substrate specificity
      suggests that this enzyme could be a potential biocatalyst for industrial lipid
      hydrolysis and conversion, particularly for biofuel production.

PMID- 23012438
TI  - A systems biology view of responses to lignin biosynthesis perturbations in
      Arabidopsis.
AB  - Lignin engineering is an attractive strategy to improve lignocellulosic biomass
      quality for processing to biofuels and other bio-based products. However, lignin
      engineering also results in profound metabolic consequences in the plant. We used
      a systems biology approach to study the plant's response to lignin perturbations.
      To this end, inflorescence stems of 20 Arabidopsis thaliana mutants, each mutated
      in a single gene of the lignin biosynthetic pathway (phenylalanine ammonia-lyase1
      [PAL1], PAL2, cinnamate 4-hydroxylase [C4H], 4-coumarate:CoA ligase1 [4CL1],
      4CL2, caffeoyl-CoA O-methyltransferase1 [CCoAOMT1], cinnamoyl-CoA reductase1
      [CCR1], ferulate 5-hydroxylase [F5H1], caffeic acid O-methyltransferase [COMT],
      and cinnamyl alcohol dehydrogenase6 [CAD6], two mutant alleles each), were
      analyzed by transcriptomics and metabolomics. A total of 566 compounds were
      detected, of which 187 could be tentatively identified based on mass spectrometry
      fragmentation and many were new for Arabidopsis. Up to 675 genes were
      differentially expressed in mutants that did not have any obvious visible
      phenotypes. Comparing the responses of all mutants indicated that c4h, 4cl1,
      ccoaomt1, and ccr1, mutants that produced less lignin, upregulated the shikimate,
      methyl-donor, and phenylpropanoid pathways (i.e., the pathways supplying the
      monolignols). By contrast, f5h1 and comt, mutants that provoked lignin
      compositional shifts, downregulated the very same pathways. Reductions in the
      flux to lignin were associated with the accumulation of various classes of 4-O-
      and 9-O-hexosylated phenylpropanoids. By combining metabolomic and transcriptomic
      data in a correlation network, system-wide consequences of the perturbations were
      revealed and genes with a putative role in phenolic metabolism were identified.
      Together, our data provide insight into lignin biosynthesis and the metabolic
      network it is embedded in and provide a systems view of the plant's response to
      pathway perturbations.

PMID- 23012439
TI  - Mutations in TMEM231 cause Joubert syndrome in French Canadians.
AB  - BACKGROUND: Joubert syndrome (JBTS) is a predominantly autosomal recessive
      disorder characterised by a distinctive midhindbrain malformation, oculomotor
      apraxia, breathing abnormalities and developmental delay. JBTS is genetically
      heterogeneous, involving genes required for formation and function of non-motile
      cilia. Here we investigate the genetic basis of JBTS in 12 French-Canadian (FC)
      individuals. METHODS AND RESULTS: Exome sequencing in all subjects showed that
      six of them carried rare compound heterozygous mutations in CC2D2A or C5ORF42,
      known JBTS genes. In addition, three individuals (two families) were compound
      heterozygous for the same rare mutations in TMEM231(c.12T>A[p.Tyr4*];  
      c.625G>A[p.Asp209Asn]). All three subjects showed a severe neurological phenotype
      and variable presence of polydactyly, retinopathy and renal cysts. These
      mutations were not detected among 385 FC controls. TMEM231 has been previously
      shown to localise to the ciliary transition zone, and to interact with several
      JBTS gene products in a complex involved in the formation of the diffusion
      barrier between the cilia and plasma membrane. siRNA knockdown of TMEM231 was
      also shown to affect barrier integrity, resulting in a reduction of cilia
      formation and ciliary localisation of signalling receptors. CONCLUSIONS: Our data
      suggest that mutations in TMEM231 cause JBTS, reinforcing the relationship
      between this condition and the disruption of the barrier at the ciliary
      transition zone.

PMID- 23012440
TI  - Redesigning and characterizing the substrate specificity and activity of Vibrio
      fluvialis aminotransferase for the synthesis of imagabalin.
AB  - Several protein engineering approaches were combined to optimize the selectivity
      and activity of Vibrio fluvialis aminotransferase (Vfat) for the synthesis of
      (3S,5R)-ethyl 3-amino-5-methyloctanoate; a key intermediate in the synthesis of
      imagabalin, an advanced candidate for the treatment of generalized anxiety
      disorder. Starting from wild-type Vfat, which had extremely low activity
      catalyzing the desired reaction, we engineered an improved enzyme with a 60-fold
      increase in initial reaction velocity for transamination of (R)-ethyl 5-methyl 3
      oxooctanoate to (3S,5R)-ethyl 3-amino-5-methyloctanoate. To achieve this, <450
      variants were screened, which allowed accurate assessment of enzyme performance
      using a low-throughput ultra performance liquid chromatography assay. During the
      course of this work, crystal structures of Vfat wild type and an improved variant
      (Vfat variant r414) were solved and they are reported here for the first time.
      This work also provides insight into the critical residues for substrate
      specificity for the transamination of (R)-ethyl 5-methyl 3-oxooctanoate and
      structurally related beta-ketoesters.

PMID- 23012441
TI  - FRETex: a FRET-based, high-throughput technique to analyze protein-protein
      interactions.
AB  - Protein-protein interactions (PPIs) are essential for cellular viability and
      activity. Here, we present a rapid, semi-quantitative method (termed FRETex) to
      analyze PPIs, taking advantage of the strong and specific FRET signal between
      fused CyPET donor and YPET acceptor molecules. To demonstrate the robustness of
      this approach, we analyzed the interactions between three protein pairs and their
      muteins: TEM1-beta-lactamase binding its inhibitor BLIP, barnase binding barstar
      and ornithine decarboxylase binding its inhibitor antizyme. The CyPET/YPET fused
      proteins were produced in small quantities, and the measurements were conducted
      directly in the proteins crude Escherichia coli lysates without any purification
      step. Protein concentrations were determined from the fluorescence intensities of
      the lysates. While binding titration curves were produced, the resulting
      affinities were not always precise. Therefore, we also conducted time-resolved
      chase experiments using non-labeled binding partners as chasers. The acquired
      dissociation rate constants were in a good agreement with those measured by
      surface plasmon resonance. Due to the simplicity of FRETex, and the ability to
      obtain semi-quantitative binding data, FRETex is a suitable method for tasks such
      as mutant scans, protein-engineering, scanning for inhibitors and more.

PMID- 23012442
TI  - Promiscuous contacts and heightened dynamics increase thermostability in an
      engineered variant of the engrailed homeodomain.
AB  - A thermostabilized variant (UVF) of the engrailed homeodomain (EnHD) was
      previously engineered by Mayo and co-workers. The melting temperature of the non
      natural, designed protein is 50 degrees C higher than the natural wild-type
      protein (>99 vs. 52 degrees C), and the two proteins share 22% sequence identity.
      We have performed extensive (1 MUs) all-atom, explicit solvent molecular dynamics
      simulations of the wild-type and engineered proteins to investigate their
      structural and dynamic properties at room temperature and at 100 degrees C. Our
      simulations are in good agreement with nuclear magnetic resonance data available
      for the two proteins [nuclear Overhauser effect crosspeaks (NOEs), J-coupling
      constants and order parameters for EnHD; and NOEs for UVF], showing that we
      reproduce the backbone dynamics and side chain packing in the native state of
      both proteins. UVF was more dynamic at room temperature than EnHD, with respect
      to both its backbone and side chain motion. When the temperature was raised, the
      thermostable protein maintained this mobility while retaining its native
      conformation. EnHD, on the other hand, was unable to maintain its more rigid
      native structure at higher temperature and began to unfold. Heightened protein
      dynamics leading to promiscuous and dynamically interchangeable amino acid
      contacts makes UVF more tolerant to increasing temperature, providing a molecular
      explanation for heightened thermostability of this protein.

PMID- 23012443
TI  - A designed bifunctional laccase/beta-1,3-1,4-glucanase enzyme shows synergistic
      sugar release from milled sugarcane bagasse.
AB  - A bifunctional enzyme has been created by fusing two Bacillus subtilis enzymes:
      the beta-1,3-1,4-glucanase (BglS, EC 3.2.1.73) that hydrolyzes plant cell wall
      beta-glucans and the copper-dependent oxidase laccase (CotA, EC 1.10.3.2) that
      catalyzes the oxidation of aromatic compounds with simultaneous reduction of
      oxygen to water. The chimeric laccase/beta-1,3-1,4-glucanase was created by
      insertion fusion of the bglS and cotA genes, and expressed in Escherichia coli.
      The affinity-purified recombinant chimeric enzyme showed both laccase and
      glucanase activities, with a maximum laccase activity at pH 4.5 and 75 degrees C
      that showed a V(max) 30% higher than observed for the parental laccase. The
      maximum glucanase activity in the chimeric enzyme was at pH 6.0 and 50 degrees C,
      with a slight reduction in V(max) by ~10% compared with the parental glucanase. A
      decreased K(M) resulted in an overall increase in the K(cat)/K(M) value for the
      glucanase activity of the chimeric enzyme. The hydrolytic activity of the chimera
      was 20% higher against natural milled sugarcane bagasse as compared with
      equimolar mixtures of the separate parental enzymes. Molecular dynamics
      simulations indicated the approximation of the two catalytic domains in the
      chimeric enzyme, and the formation of an inter-domain interface may underlie the
      improved catalytic function.

PMID- 23012444
TI  - Long term outcome after conservative and surgical treatment of haemorrhagic
      moyamoya disease.
AB  - OBJECTIVE: To investigate the long term outcomes after conservative and surgical
      treatment for haemorrhagic moyamoya disease. METHODS: 97 consecutive patients
      with haemorrhagic moyamoya disease from 1997 to 2009 were enrolled in this study
      (mean age 31+/-10 years; range 5-56 years). We reviewed the clinical charts and
      radiographs of patients at the first bleeding episode. Follow-up was obtained
      prospectively by questionnaires and radiographic examinations. Outcomes were
      compared based on initial treatment (conservative vs surgical). RESULTS: After a
      median follow-up of 7.1 years, 21 of the 97 (21.7%) patients developed a second
      episode of bleeding, and six patients (6.2%) died of intracranial rebleeding. The
      median interval from initial episode to subsequent rebleeding was 9.1 years (0.1
      23.2 years). 17 of 43 (37.1%) conservatively treated patients and four of 54
      (7.4%) surgically treated patients experienced a rebleeding event (OR 8.1; 95% CI
      2.4 to 26.8; p<0.001). There was a difference in the Kaplan-Meier curve of
      rebleeding between the two groups (Breslow test p=0.047; log rank test p=0.05).
      The rebleeding ratio in patients who underwent direct bypass was lower than that
      in patients treated with indirect bypass alone (0% vs 28.5%, 95% CI 1.0 to 1.9;
      p=0.002). No significant correlation was found between rebleeding and the
      patient's age, sex, location of haemorrhage, hypertension status or presence of
      cerebral aneurysm (p>0.05). CONCLUSIONS: There is a high risk of rebleeding after
      the first haemorrhagic episode in Chinese patients with haemorrhagic moyamoya
      disease. Revascularisation surgery can improve regional blood flow and have
      greater efficacy at preventing rebleeding than conservative treatment.

PMID- 23012445
TI  - Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat
      expansion in C9ORF72.
AB  - BACKGROUND: A GGGGCC hexanucleotide repeat expansion in C9ORF72 occurs on a
      chromosome 9p21 locus that is linked with frontotemporal dementia (FTD) and
      amyotrophic lateral sclerosis (ALS) in white populations. The diseases resulting
      from this expansion are referred to as 'c9FTD/ALS'. It has been suggested that
      c9FTD/ALS arose from a single founder. However, the existence of c9FTD/ALS in non
      white populations has not been evaluated. RESULTS: We found two index familial
      ALS (FALS) patients with c9FTD/ALS in the Japanese population. The frequency of
      c9FTD/ALS was 3.4% (2/58 cases) in FALS. No patients with sporadic ALS (n=110) or
      control individuals (n=180) had the expansion. Neuropathological findings of an
      autopsy case were indistinguishable from those of white patients. Although the
      frequency of risk alleles identified in white subjects is low in Japanese, one
      patient had all 20 risk alleles and the other had all but one. The estimated
      haplotype indicated that the repeat expansion in these patients was located on
      the chromosome with the risk haplotype identified in white subjects. CONCLUSIONS:
      C9ORF72 repeat expansions were present in a Japanese cohort of ALS patients, but
      they were rare. Intriguingly, Japanese patients appear to carry the same risk
      haplotype identified in white populations.

PMID- 23012446
TI  - Early neurological deterioration after subarachnoid haemorrhage: risk factors and
      impact on outcome.
AB  - BACKGROUND: Early neurological deterioration occurs frequently after subarachnoid
      haemorrhage (SAH). The impact on hospital course and outcome remains poorly
      defined. METHODS: We identified risk factors for worsening on the Hunt-Hess
      grading scale within the first 24 h after admission in 609 consecutively admitted
      aneurysmal SAH patients. Admission risk factors and the impact of early worsening
      on outcome was evaluated using multivariable analysis adjusting for age, gender,
      admission clinical grade, admission year and procedure type. Outcome was
      evaluated at 12 months using the modified Rankin Scale (mRS). RESULTS: 211
      patients worsened within the first 24 h of admission (35%). In a multivariate
      adjusted model, early worsening was associated with older age (OR 1.02, 95% CI
      1.001 to 1.03; p=0.04), the presence of intracerebral haematoma on initial CT
      scan (OR 2.0, 95% CI 1.2 to 3.5; p=0.01) and higher SAH and intraventricular
      haemorrhage sum scores (OR 1.05, 95% CI 1.03 to 1.08 and 1.1, 95% CI 1.01 to 1.2;
      p<0.001 and 0.03, respectively). Early worsening was associated with more
      hospital complications and prolonged length of hospital stay and was an
      independent predictor of death (OR 12.1, 95% CI 5.7 to 26.1; p<0.001) and death
      or moderate to severe disability (mRS 4-6, OR 8.4, 95% CI 4.9 to 14.5; p=0.01) at
      1 year. CONCLUSIONS: Early worsening after SAH occurs in 35% of patients, is
      predicted by clot burden and is associated with mortality and poor functional
      outcome at 1 year.

PMID- 23012447
TI  - Safety and occlusion rates of surgical treatment of unruptured intracranial
      aneurysms: a systematic review and meta-analysis of the literature from 1990 to
      2011.
AB  - BACKGROUND AND PURPOSE: Surgical clipping of unruptured intracranial aneurysms
      (UIAs) has recently been challenged by the emergence of endovascular treatment.
      We performed an updated systematic review and meta-analysis on the surgical
      treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and
      safety of surgery in the modern era. METHODS: A detailed protocol was developed
      prior to conducting the review according to the Cochrane Collaboration
      guidelines. Electronic databases spanning January 1990-April 2011 were searched,
      complemented by hand searching. Heterogeneity was assessed using I(2), and
      publication bias with funnel plots. Surgical mortality and morbidity were
      analysed with weighted random effect models. RESULTS: 60 studies with 9845
      patients harbouring 10 845 aneurysms were included. Mortality occurred in 157
      patients (1.7%; 99% CI 0.9% to 3.0%; I(2)=82%). Unfavourable outcomes, including
      death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I(2)=85%). Morbidity
      rates were significantly greater in higher quality studies, and with large or
      posterior circulation aneurysms. Reported morbidity rates decreased over time.
      Studies were generally of poor quality; funnel plots showed heterogeneous results
      and publication bias, and data on aneurysm occlusion rates were scant.
      CONCLUSIONS: In studies published between 1990 and 2011, clipping of UIAs was
      associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability
      of clipping has not been rigorously documented. Due to the quality of the
      included studies, the available literature cannot properly guide clinical
      decisions.

PMID- 23012448
TI  - A unified formula for light-adapted pupil size.
AB  - The size of the pupil has a large effect on visual function, and pupil size
      depends mainly on the adapting luminance, modulated by other factors. Over the
      last century, a number of formulas have been proposed to describe this
      dependence. Here we review seven published formulas and develop a new unified
      formula that incorporates the effects of luminance, size of the adapting field,
      age of the observer, and whether one or both eyes are adapted. We provide
      interactive demonstrations and software implementations of the unified formula.

PMID- 23012449
TI  - Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor
      B promotes lymphatic metastasis of hypoxic breast cancer cells.
AB  - Lymphatic dissemination from the primary tumor is a major mechanism by which
      breast cancer cells access the systemic circulation, resulting in distant
      metastasis and mortality. Numerous studies link activation of hypoxia-inducible
      factor 1 (HIF-1) with tumor angiogenesis, metastasis, and patient mortality.
      However, the role of HIF-1 in lymphatic dissemination is poorly understood. In
      this study, we show that HIF-1 promotes lymphatic metastasis of breast cancer by
      direct transactivation of the gene encoding platelet-derived growth factor B
      (PDGF-B), which has proliferative and chemotactic effects on lymphatic
      endothelial cells. Lymphangiogenesis and lymphatic metastasis in mice bearing
      human breast cancer orthografts were blocked by administration of the HIF-1
      inhibitor digoxin or the tyrosine kinase inhibitor imatinib. Immunohistochemical
      analysis of human breast cancer biopsies demonstrated colocalization of HIF
      1alpha and PDGF-B, which were correlated with lymphatic vessel area and
      histological grade. Taken together, these data provide experimental support for
      breast cancer clinical trials targeting HIF-1 and PDGF-B.

PMID- 23012450
TI  - Distinct mTORC1 pathways for transcription and cleavage of SREBP-1c.

PMID- 23012451
TI  - Long-term effects of adolescent-onset and persistent use of cannabis.

PMID- 23012452
TI  - Dicyanovinylnaphthalenes for neuroimaging of amyloids and relationships of
      electronic structures and geometries to binding affinities.
AB  - The positron-emission tomography (PET) probe 2-(1-[6-[(2
      fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) (FDDNP) is used for the
      noninvasive brain imaging of amyloid-beta (Abeta) and other amyloid aggregates
      present in Alzheimer's disease and other neurodegenerative diseases. A series of
      FDDNP analogs has been synthesized and characterized using spectroscopic and
      computational methods. The binding affinities of these molecules have been
      measured experimentally and explained through the use of a computational model.
      The analogs were created by systematically modifying the donor and the acceptor
      sides of FDDNP to learn the structural requirements for optimal binding to Abeta
      aggregates. FDDNP and its analogs are neutral, environmentally sensitive,
      fluorescent molecules with high dipole moments, as evidenced by their
      spectroscopic properties and dipole moment calculations. The preferred solution
      state conformation of these compounds is directly related to the binding
      affinities. The extreme cases were a nonplanar analog t-butyl-FDDNP, which shows
      low binding affinity for Abeta aggregates (520 nM K(i)) in vitro and a nearly
      planar tricyclic analog cDDNP, which displayed the highest binding affinity (10
      pM K(i)). Using a previously published X-ray crystallographic model of 1,1
      dicyano-2-[6-(dimethylamino)naphthalen-2-yl]propene (DDNP) bound to an
      amyloidogenic Abeta peptide model, we show that the binding affinity is inversely
      related to the distortion energy necessary to avoid steric clashes along the
      internal surface of the binding channel.

PMID- 23012453
TI  - Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to
      endogenous and exogenous antimicrobials.
AB  - Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients
      and have failed to control tuberculosis globally. One reason may be that host
      conditions impair Mtb's replication, reducing its sensitivity to most
      antiinfectives. We devised a high-throughput screen for compounds that kill Mtb
      when its replication has been halted by reactive nitrogen intermediates (RNIs),
      acid, hypoxia, and a fatty acid carbon source. At concentrations routinely
      achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory
      drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal
      activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and
      RNIs fostered OPB's 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4
      hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating
      and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins
      and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed
      Mtb synergistically with oxidants and several antituberculosis drugs. Thus,
      conditions that block Mtb's replication modify OPB and enhance its cidal action.
      Modified OPB kills both replicating and NR Mtb and sensitizes both to host
      derived and medicinal antimycobacterial agents.

PMID- 23012454
TI  - bHLH-PAS heterodimer of methoprene-tolerant and Cycle mediates circadian
      expression of juvenile hormone-induced mosquito genes.
AB  - Juvenile hormone (JH) governs a great diversity of processes in insect
      development and reproduction. It plays a critical role in controlling the
      gonadotrophic cycles of female mosquitoes by preparing tissues for blood
      digestion and egg development. Here, we show that in female Aedes aegypti
      mosquitoes JH III control of gene expression is mediated by a heterodimer of two
      bHLH-PAS proteins-the JH receptor methoprene-tolerant (MET) and Cycle (CYC,
      AAEL002049). We identified Aedes CYC as a MET-interacting protein using yeast two
      hybrid screening. Binding of CYC and MET required the presence of JH III. In
      newly eclosed female mosquitoes, the expression of two JH-responsive genes, Kr-h1
      and Hairy, was dependent on both the ratio of light to dark periods and JH III.
      Their expression was compromised by in vivo RNA interference (RNAi) depletions of
      CYC, MET, and the steroid receptor coactivator SRC/FISC. Moreover, JH III was not
      effective in induction of Kr-h1 and Hairy gene expression in vitro in fat bodies
      of female mosquitoes with RNAi-depleted CYC, MET or SRC/FISC. A sequence
      containing an E-box-like motif from the Aedes Kr-h1 gene promoter specifically
      interacted with a protein complex, which included MET and CYC from the female
      mosquito fat body nuclear extract. These results indicate that a MET/CYC
      heterodimer mediates JH III activation of Kr-h1 and Hairy genes in the context of
      light-dependent circadian regulation in female mosquitoes during posteclosion
      development. This study provides an important insight into the understanding of
      the molecular basis of JH action.

PMID- 23012455
TI  - Calcium with the beta-tin structure at high pressure and low temperature.
AB  - Using synchrotron high-pressure X-ray diffraction at cryogenic temperatures, we
      have established the phase diagram for calcium up to 110 GPa and 5-300 K. We
      discovered the long-sought for theoretically predicted beta-tin structured
      calcium with I4(1)/amd symmetry at 35 GPa in a s mall low-temperature range below
      10 K, thus resolving the enigma of absence of this lowest enthalpy phase. The
      stability and relations among various distorted simple-cubic phases in the Ca-III
      region have also been examined and clarified over a wide range of high pressures
      and low temperatures.

PMID- 23012456
TI  - An unusual phosphatidylethanolamine-utilizing cardiolipin synthase is discovered
      in bacteria.

PMID- 23012457
TI  - Impairment of O-antigen production confers resistance to grazing in a model
      amoeba-cyanobacterium predator-prey system.
AB  - The grazing activity of predators on photosynthetic organisms is a major
      mechanism of mortality and population restructuring in natural environments.
      Grazing is also one of the primary difficulties in growing cyanobacteria and
      other microalgae in large, open ponds for the production of biofuels, as
      contaminants destroy valuable biomass and prevent stable, continuous production
      of biofuel crops. To address this problem, we have isolated a heterolobosean
      amoeba, HGG1, that grazes upon unicellular and filamentous freshwater
      cyanobacterial species. We have established a model predator-prey system using
      this amoeba and Synechococcus elongatus PCC 7942. Application of amoebae to a
      library of mutants of S. elongatus led to the identification of a grazer
      resistant knockout mutant of the wzm ABC O-antigen transporter gene,
      SynPCC7942_1126. Mutations in three other genes involved in O-antigen synthesis
      and transport also prevented the expression of O-antigen and conferred resistance
      to HGG1. Complementation of these rough mutants returned O-antigen expression and
      susceptibility to amoebae. Rough mutants are easily identifiable by appearance,
      are capable of autoflocculation, and do not display growth defects under standard
      laboratory growth conditions, all of which are desired traits for a biofuel
      production strain. Thus, preventing the production of O-antigen is a pathway for
      producing resistance to grazing by certain amoebae.

PMID- 23012460
TI  - Solid breast lesions: clinical experience with US-guided diffuse optical
      tomography combined with conventional US.
AB  - PURPOSE: To prospectively investigate the clinical efficacy of using diffuse
      optical tomography (DOT) and ultrasonographic (US) localization with conventional
      US to differentiate malignant solid breast lesions from those that are benign.
      MATERIALS AND METHODS: The study was approved by the institutional review board
      and all patients provided written informed consent. One hundred two consecutive
      women (mean age, 43 years; range, 18-86 years) who were referred for open biopsy
      with 136 breast lesions underwent conventional US and DOT with US localization.
      Total hemoglobin concentration and oxygen saturation were measured for each
      breast lesion. Sensitivity, specificity, overall accuracy, positive predictive
      value, and negative predictive value were determined with surgical pathologic
      examination results as the verification standard. RESULTS: Of the 136 biopsied
      lesions, 54 were carcinomas and 82 were benign. The average total hemoglobin
      concentration in the malignant group was 223.3 MUmol/L+/-55.8 (standard
      deviation), and the average hemoglobin concentration in the benign group was
      122.5 MUmol/L+/-80.6 (P=.005). When the maximum hemoglobin concentration of 137.8
      MUmol/L was used as the threshold value, the sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy of DOT with US
      localization were 96.3%, 65.9%, 65.0%, 96.4%, and 76.5%, respectively. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of conventional US were 96.3%, 92.6%, 89.7%, 97.4%, and 93.4%,
      respectively. The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of conventional US combined with DOT were 100%,
      93.9%, 91.5%, 100%, and 96.3%, respectively. CONCLUSION: US-guided DOT combined
      with conventional US improves accuracy compared with DOT alone.

PMID- 23012458
TI  - Retinoic acid induces Sertoli cell paracrine signals for spermatogonia
      differentiation but cell autonomously drives spermatocyte meiosis.
AB  - Direct evidence for a role of endogenous retinoic acid (RA), the active
      metabolite of vitamin A in the initial differentiation and meiotic entry of
      spermatogonia, and thus in the initiation of spermatogenesis is still lacking. RA
      is synthesized by dedicated enzymes, the retinaldehyde dehydrogenases (RALDH),
      and binds to and activates nuclear RA receptors (RARA, RARB, and RARG) either
      within the RA-synthesizing cells or in the neighboring cells. In the present
      study, we have used a combination of somatic genetic ablations and
      pharmacological approaches in vivo to show that during the first, prepubertal,
      spermatogenic cycle (i) RALDH-dependent synthesis of RA by Sertoli cells (SC),
      the supporting cells of the germ cell (GC) lineage, is indispensable to initiate
      differentiation of A aligned into A1 spermatogonia; (ii) RARA in SC mediates the
      effects of RA, possibly through activating Mafb expression, a gene whose
      Drosophila homolog is mandatory to GC differentiation; (iii) RA synthesized by
      premeiotic spermatocytes cell autonomously induces meiotic initiation through
      controlling the RAR-dependent expression of Stra8. Furthermore, we show that RA
      of SC origin is no longer necessary for the subsequent spermatogenic cycles but
      essential to spermiation. Altogether, our data establish that the effects of RA
      in vivo on spermatogonia differentiation are indirect, via SC, but direct on
      meiotic initiation in spermatocytes, supporting thereby the notion that, contrary
      to the situation in the female, RA is necessary to induce meiosis in the male.

PMID- 23012461
TI  - Differentiation of early from advanced coronary atherosclerotic lesions:
      systematic comparison of CT, intravascular US, and optical frequency domain
      imaging with histopathologic examination in ex vivo human hearts.
AB  - PURPOSE: To establish an ex vivo experimental setup for imaging coronary
      atherosclerosis with coronary computed tomographic (CT) angiography,
      intravascular ultrasonography (US), and optical frequency domain imaging (OFDI)
      and to investigate their ability to help differentiate early from advanced
      coronary plaques. MATERIALS AND METHODS: All procedures were performed in
      accordance with local and federal regulations and the Declaration of Helsinki.
      Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts
      from nine coronary arteries from three donor hearts were acquired, coregistered
      among modalities, and assessed for the presence and composition of
      atherosclerotic plaque. To assess the discriminatory capacity of the different
      modalities in the detection of advanced lesions, c statistic analysis was used.
      Interobserver agreement was assessed with the Cohen kappa statistic. RESULTS:
      Cross sections without plaque at coronary CT angiography and with fibrous plaque
      at OFDI almost never showed advanced lesions at histopathologic examination (odds
      ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at
      coronary CT angiography, calcified plaque at intravascular US, and lipid-rich
      plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR:
      2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for
      discriminating early from advanced lesions than intravascular US and coronary CT
      angiography (area under the receiver operating characteristic curve: 0.858 [95%
      confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679
      [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was
      excellent for OFDI and coronary CT angiography (kappa=0.87 and 0.85,
      respectively) and was good for intravascular US (kappa=0.66). CONCLUSION:
      Systematic and standardized comparison between invasive and noninvasive
      modalities for coronary plaque characterization in ex vivo specimens demonstrated
      that coronary CT angiography and intravascular US are reasonably associated with
      plaque composition and lesion grading according to histopathologic findings,
      while OFDI was strongly associated. These data may help to develop initial
      concepts of sequential imaging strategies to identify patients with advanced
      coronary plaques.

PMID- 23012462
TI  - Progressive supranuclear palsy: in vivo SPECT imaging of presynaptic vesicular
      acetylcholine transporter with [123I]-iodobenzovesamicol.
AB  - PURPOSE: To evaluate the integrity of brain cholinergic pathways in vivo in
      patients with progressive supranuclear palsy (PSP) by measuring the vesicular
      acetylcholine transporter expression at single photon emission computed
      tomography (SPECT) with [123I]-iodobenzovesamicol. MATERIALS AND METHODS: All
      participants provided informed written consent according to institutional human
      ethics committee guidelines. Ten patients with PSP and 12 healthy volunteers
      underwent dynamic [123I]-iodobenzovesamicol SPECT and magnetic resonance (MR)
      imaging. CT and MR images were used to register the dynamic SPECT image to the
      Montreal Neurologic Institute brain template, which includes the regions of
      interest of the striatum and the septo-hippocampal, innominato-cortical, and
      ponto-thalamic cholinergic pathways. For each region of interest, pharmacokinetic
      modeling of regional time activity curves was used to calculate [123I]
      iodobenzovesamicol to vesicular acetylcholine transporter binding potential
      value, proportional to vesicular acetylcholine transporter expression. RESULTS:
      When compared with control participants, patients with PSP had binding potential
      values that were unchanged in the striatum and septohippocampal pathway,
      significantly lower in the anterior cingulate cortex (P=.017) in the
      innominatocortical pathway, and significantly decreased in the thalamus (P=.014)
      in the pontothalamic cholinergic pathway. In addition, binding potential values
      in the thalamus were positively correlated with those in the pedunculopontine
      nucleus (rho=0.81, P<.004) and binding potential values in both the thalamus
      (rho=-0.88, P<.001) and pedunculopontine nucleus (rho=-0.80, P<.010) were
      inversely correlated with disease duration. CONCLUSION: Cholinergic pathways were
      differentially affected in the PSP group, with a significant alteration of
      pontothalamic pathways that increased with disease progression at both cell body
      and terminal levels, while the innominatocortical pathway was only mildly
      affected, and the septohippocampal pathway and the striatum were both preserved.

PMID- 23012463
TI  - Angiomyolipoma with minimal fat: can it be differentiated from clear cell renal
      cell carcinoma by using standard MR techniques?
AB  - PURPOSE: To retrospectively assess whether magnetic resonance (MR) imaging with
      opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis
      can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell
      renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses.
      MATERIALS AND METHODS: Institutional review board approval and a waiver of
      informed consent were obtained for this HIPAA-compliant study. MR images from 108
      pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs
      from 64 men and 44 women) at two academic institutions were evaluated. The signal
      intensity (SI) of each renal mass and spleen on opposed-phase and in-phase GRE
      images was used to calculate an SI index and tumor-to-spleen SI ratio. Two
      radiologists who were blinded to the pathologic results independently assessed
      the subjective presence of intravoxel fat (ie, decreased SI on opposed-phase
      images compared with that on in-phase images), SI on T1-weighted and T2-weighted
      images, cystic degeneration, necrosis, hemorrhage, retroperitoneal collaterals,
      and renal vein thrombosis. Results were analyzed by using the Wilcoxon rank sum
      test, two-tailed Fisher exact test, and multivariate logistic regression analysis
      for all renal masses and for small masses. A P value of less than .05 was
      considered to indicate a statistically significant difference. RESULTS: There
      were no differences between minimal fat AMLs and clear cell RCCs for the SI index
      (8.05%+/-14.46 vs 14.99%+/-19.9; P=.146) or tumor-to-spleen ratio (-8.96%+/-16.6
      and -15.8%+/-22.4; P=.227) when all masses or small masses were analyzed.
      Diagnostic accuracy (area under receiver operating characteristic curve) for the
      SI index and tumor-to-spleen ratio was 0.59. Intratumoral necrosis and larger
      size were predictive of clear cell RCC (P<.001) for all lesions, whereas low SI
      (relative to renal parenchyma SI) on T2-weighted images, smaller size, and female
      sex correlated with minimal fat AML (P<.001) for all lesions. CONCLUSION: The
      diagnostic accuracy of opposed-phase and in-phase GRE MR imaging for the
      differentiation of minimal fat AML and clear cell RCC is poor. In this cohort,
      low SI on T2-weighted images relative to renal parenchyma and small size
      suggested minimal fat AML, whereas intratumoral necrosis and large size argued
      against this diagnosis.

PMID- 23012464
TI  - Coil-treated aneurysms: decision making regarding additional treatment based on
      findings of MR angiography and intraarterial DSA.
AB  - PURPOSE: To assess whether magnetic resonance (MR) angiography can be used as a
      noninvasive alternative to intraarterial digital subtraction angiography (DSA) to
      indicate additional treatment in the follow-up of patients with coil-treated
      intracranial aneurysms. MATERIALS AND METHODS: This was an ethics committee
      approved multicenter study. Consecutive patients who were scheduled for follow-up
      intraarterial DSA after coil placement were invited for additional MR angiography
      after providing written informed consent. Interventional neuroradiologists gave
      treatment advice (additional treatment, extended follow-up imaging, or discharge
      from follow-up) for each imaging modality. Agreement between treatment advices
      based on intraarterial DSA and MR angiographic findings and interobserver
      agreement were assessed with weighted kappa statistics. RESULTS: Agreement
      between intraarterial DSA- and MR angiography-based treatment recommendations was
      substantial (kappa = 0.73; 95% confidence interval [CI]: 0.66, 0.80). In 34 of
      the 310 patients (11%), the advice was additional treatment based on findings of
      both modalities. In six patients (2%), the advice based on intraarterial DSA
      findings was additional treatment, while that based on MR angiographic findings
      was extended follow-up imaging; therefore, none of these patients were discharged
      from follow-up on the basis of MR angiographic findings. In six other patients
      (2%), the advice based on MR angiographic findings was additional treatment,
      while that based on intraarterial DSA findings was extended follow-up imaging
      (four patients), discharge from follow-up (one patient), and noninterpretable DSA
      (one patient). Extended follow-up imaging was suggested for 37 patients (12%)
      after intraarterial DSA and for 49 patients (16%) after MR angiography
      (difference: 4%; 95% CI: -0.6%, 8.4%). Interobserver agreement was substantial
      for intraarterial DSA (kappa = 0.73; 95% CI: 0.64, 0.82) and moderate for MR
      angiography (kappa = 0.53; 95% CI: 0.36, 0.70). CONCLUSION: The overall
      proportion of patients advised to undergo additional treatment is similar based
      on intraarterial DSA and MR angiographic findings, with only few individual
      discrepancies. MR angiography can therefore be used for therapeutic decision
      making in the follow-up of patients with coil-treated aneurysms. SUPPLEMENTAL
      MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112608/
      /DC1.

PMID- 23012465
TI  - MR thermometry analysis of sonication accuracy and safety margin of volumetric MR
      imaging-guided high-intensity focused ultrasound ablation of symptomatic uterine
      fibroids.
AB  - PURPOSE: To evaluate the accuracy of the size and location of the ablation zone
      produced by volumetric magnetic resonance (MR) imaging-guided high-intensity
      focused ultrasound ablation of uterine fibroids on the basis of MR thermometric
      analysis and to assess the effects of a feedback control technique. MATERIALS AND
      METHODS: This prospective study was approved by the institutional review board,
      and written informed consent was obtained. Thirty-three women with 38 uterine
      fibroids were treated with an MR imaging-guided high-intensity focused ultrasound
      system capable of volumetric feedback ablation. Size (diameter times length) and
      location (three-dimensional displacements) of each ablation zone induced by 527
      sonications (with [n=471] and without [n=56] feedback) were analyzed according to
      the thermal dose obtained with MR thermometry. Prospectively defined acceptance
      ranges of targeting accuracy were +/-5 mm in left-right (LR) and craniocaudal
      (CC) directions and +/-12 mm in anteroposterior (AP) direction. Effects of
      feedback control in 8- and 12-mm treatment cells were evaluated by using a mixed
      model with repeated observations within patients. RESULTS: Overall mean sizes of
      ablation zones produced by 4-, 8-, 12-, and 16-mm treatment cells (with and
      without feedback) were 4.6 mm+/-1.4 (standard deviation)*4.4 mm+/-4.8 (n=13), 8.9
      mm+/-1.9*20.2 mm+/-6.5 (n=248), 13.0 mm+/-1.2*29.1 mm+/-5.6 (n=234), and 18.1
      mm+/-1.4*38.2 mm+/-7.6 (n=32), respectively. Targeting accuracy values
      (displacements in absolute values) were 0.9 mm+/-0.7, 1.2 mm+/-0.9, and 2.8 mm+/
      2.2 in LR, CC, and AP directions, respectively. Of 527 sonications, 99.8% (526 of
      527) were within acceptance ranges. Feedback control had no statistically
      significant effect on targeting accuracy or ablation zone size. However,
      variations in ablation zone size were smaller in the feedback control group.
      CONCLUSION: Sonication accuracy of volumetric MR imaging-guided high-intensity
      focused ultrasound ablation of uterine fibroids appears clinically acceptable and
      may be further improved by feedback control to produce more consistent ablation
      zones.

PMID- 23012466
TI  - Incremental diagnostic value of SPECT/CT with 131I scintigraphy after radioiodine
      therapy in patients with well-differentiated thyroid carcinoma.
AB  - PURPOSE: To retrospectively determine the incremental diagnostic value of adding
      single photon emission computed tomography/computed tomography (SPECT/CT) to
      whole-body scintigraphy with iodine 131 ((131)I) compared with scintigraphy alone
      after radioiodine therapy in patients with well-differentiated thyroid carcinoma.
      MATERIALS AND METHODS: This retrospective study was institutional review board
      approved; written informed consent was waived. The study included 147 patients
      (94 female, 53 male patients; mean age, 51 years) with well-differentiated
      thyroid carcinoma treated with radioiodine therapy between October 2009 and
      August 2010. Whole-body scintigraphy and SPECT/CT were performed on the same day
      in all patients receiving radioiodine therapy. Each radioactive focus at whole
      body scintigraphy was classified as positive or equivocal with respect to thyroid
      bed, lymph node, and distant metastasis uptake. Differences between whole-body
      scintigraphy and SPECT/CT findings were assessed with the generalized McNemar
      test. RESULTS: At SPECT/CT, origin was clearly determined of all five "hot spots"
      in the thyroid bed (remnant thyroid tissue or metastatic lymph node) that were
      judged as equivocal at whole-body scintigraphy. Interpretation of 24 (22.2%) of
      108 radioactive foci for lymph node metastases was changed with SPECT/CT (P <
      .0001). One of 85 foci that were thought to be positive findings at whole-body
      scintigraphy turned out to be a negative finding (false-positive finding), and 13
      and seven of 20 equivocal foci at whole-body scintigraphy were positive and
      negative findings, respectively, after adding SPECT/CT findings. Three false
      negative findings at whole-body scintigraphy were corrected with SPECT/CT. For
      the detection of distant metastasis, the interpretations of 21 (40%) of 52 foci
      were corrected with SPECT/CT (P < .0001). One of 32 foci thought to be a positive
      finding at whole-body scintigraphy was a negative finding, and 11 and nine of 20
      equivocal foci at whole-body scintigraphy were positive and negative findings,
      respectively, after SPECT/CT. At a patient-based analysis, SPECT/CT findings
      helped change the clinical staging in nine (6.1%) of 147 patients and therapeutic
      planning in three (2.0%) of 147 patients. CONCLUSION: SPECT/CT improved detection
      and localization of (131)I accumulation in lymph node metastases and distant
      metastases, compared with whole-body scintigraphy.

PMID- 23012468
TI  - Incidence, prevalence and clinical characteristics of Behcet's disease in
      southern Sweden.
AB  - OBJECTIVE: To study the incidence, prevalence and clinical characteristics of
      Behcet's disease (BD) in a defined population in southern Sweden. METHODS: The
      study area consists of three health-care districts with an adult population (>=15
      years) of 809 317 on 1 January 2011 (25% of non-Swedish ancestry), situated in
      Skane, the southernmost county in Sweden. Patients were identified using clinical
      registries in all the five hospitals within the study area. Only patients
      fulfilling the International Study Group criteria for diagnosis of BD were
      included. RESULTS: Forty patients (13 women) fulfilling the diagnosis criteria
      for BD (70% of non-Swedish ancestry) were identified. The point prevalence of BD
      on 1 January 2011 was 4.9/100,000 adults (95% CI 3.4, 6.5) and was higher among
      the population of non-Swedish ancestry (13.6 vs 2.0/100,000, P < 0.001), and
      higher among men (6.8 vs 3.2/100,000, P = 0.019). There were 20 incident cases
      (diagnosed in Sweden between 1997 and 2010). The annual incidence rate was
      0.2/100,000 adults (95% CI 0.1, 0.3) and was higher among the population of non
      Swedish ancestry (0.6 vs 0.1/100,000, P < 0.001). The incidence was 0.3/100,000
      adults in men and 0.1/100,000 in women, P = 0.143. During the course of the
      disease, 100% of the patients developed oral ulceration, 80% genital ulcers, 88%
      skin lesions, 53% eye disease, 40% arthritis/arthralgia and 20% venous
      thrombosis. CONCLUSION: The prevalence of BD is higher in Sweden than previously
      reported, mainly due to immigration. The incidence of BD remains elevated for
      immigrants from high-prevalence regions even long after settling in Sweden.

PMID- 23012467
TI  - Attenuation-based automatic tube voltage selection and tube current modulation
      for dose reduction at contrast-enhanced liver CT.
AB  - PURPOSE: To retrospectively determine whether the combined use of automatic tube
      voltage selection (ATVS) and automatic tube current modulation (ATCM) can
      effectively reduce radiation dose at contrast material-enhanced liver computed
      tomography (CT) while maintaining acceptable image quality compared with the use
      of ATCM alone. MATERIALS AND METHODS: This study was approved by an institutional
      review board, and informed consent was waived. Three hundred fourteen consecutive
      patients suspected of having liver disease were divided into three groups. In two
      groups, both ATVS and ATCM were used (group A1, n=97; group A2, n=101) but with
      different contrast gain settings; in one group, only ATCM with a fixed tube
      potential of 120 kV (group B, n=116) was used. Weighted volume CT dose index and
      dose-length product, contrast-to-noise ratios (CNRs), and mean image noise were
      assessed. Qualitative analysis was performed by two board-certified radiologists
      and one radiology resident. Statistical analysis was performed by using the one
      way analysis of variance test, two-tailed paired t test, Kruskal-Wallis test, and
      noninferiority test. RESULTS: In groups A1 and A2, a significant dose reduction
      was obtained compared with that in group B (P<.0001). The mean dose reduction was
      20% in group A1 and 31% in group A2. Furthermore, CNRs were significantly higher
      in groups A1 and A2 than in group B (P<.0001). Despite the higher image noise in
      groups A1 and A2, the overall image quality was acceptable. CONCLUSION: Compared
      with the use of ATCM alone, the combined use of ATVS and ATCM allowed reduction
      of radiation exposure while maintaining good image quality at contrast-enhanced
      liver CT.

PMID- 23012469
TI  - H2/CH4 ratios cannot reliably distinguish abiotic vs. biotic methane in natural
      hydrothermal systems.

PMID- 23012470
TI  - Complex oncogene dependence in microRNA-125a-induced myeloproliferative
      neoplasms.
AB  - Deregulation of microRNA (miRNA) expression can lead to cancer initiation and
      progression. However, limited information exists on the function of miRNAs in
      cancer maintenance. We examined these issues in the case of myeloproliferative
      diseases and neoplasms (MPN), a collection of hematopoietic neoplasms regarded as
      preleukemic, thereby representing early neoplastic states. We report here that
      microRNA-125a (miR-125a)-induced MPN display a complex manner of oncogene
      dependence. Following a gain-of-function genomics screen, we overexpressed
      candidate miR-125a in vivo, which led to phenotypes consistent with an atypical
      MPN characterized by leukocytosis, monocytosis, splenomegaly, and progressive
      anemia. The diseased MPN state could be recapitulated in a doxycycline-inducible
      mouse model. Upon doxycycline withdrawal, the primary MPN phenotypes rapidly
      resolved after the discontinuation of miR-125a overexpression. However,
      reinduction of miR-125a led to complex phenotypes, with some animals rapidly
      developing lethal anemia with extensive damages in the spleen. Forced expression
      of miR-125a resulted in elevated cellular tyrosine phosphorylation and
      hypersensitivity toward hematopoietic cytokines. Furthermore, we demonstrate that
      miR-125a targets multiple protein phosphatases. Our data demonstrate that miR
      125a-induced MPN is addicted to its sustained overexpression, and highlight the
      complex nature of oncogenic miRNA dependence in an early neoplastic state.

PMID- 23012471
TI  - Shrinking majority of the deep biosphere.

PMID- 23012472
TI  - Cyclic AMP-dependent phosphorylation of neuronal nitric oxide synthase mediates
      penile erection.
AB  - Nitric oxide (NO) generated by neuronal NO synthase (nNOS) initiates penile
      erection, but has not been thought to participate in the sustained erection
      required for normal sexual performance. We now show that cAMP-dependent
      phosphorylation of nNOS mediates erectile physiology, including sustained
      erection. nNOS is phosphorylated by cAMP-dependent protein kinase (PKA) at
      serine(S)1412. Electrical stimulation of the penile innervation increases S1412
      phosphorylation that is blocked by PKA inhibitors but not by PI3-kinase/Akt
      inhibitors. Stimulation of cAMP formation by forskolin also activates nNOS
      phosphorylation. Sustained penile erection elicited by either intracavernous
      forskolin injection, or augmented by forskolin during cavernous nerve electrical
      stimulation, is prevented by the NOS inhibitor L-NAME or in nNOS-deleted mice.
      Thus, nNOS mediates both initiation and maintenance of penile erection, implying
      unique approaches for treating erectile dysfunction.

PMID- 23012473
TI  - Structure of the cleavage-activated prefusion form of the parainfluenza virus 5
      fusion protein.
AB  - The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by fusion of the
      viral envelope with the plasma membrane through the concerted action of the
      fusion (F) protein and the receptor binding protein hemagglutinin-neuraminidase.
      The F protein folds initially to form a trimeric metastable prefusion form that
      is triggered to undergo large-scale irreversible conformational changes to form
      the trimeric postfusion conformation. It is thought that F refolding couples the
      energy released with membrane fusion. The F protein is synthesized as a precursor
      (F0) that must be cleaved by a host protease to form a biologically active
      molecule, F1,F2. Cleavage of F protein is a prerequisite for fusion and virus
      infectivity. Cleavage creates a new N terminus on F1 that contains a hydrophobic
      region, known as the FP, which intercalates target membranes during F protein
      refolding. The crystal structure of the soluble ectodomain of the uncleaved form
      of PIV5 F is known; here we report the crystal structure of the cleavage
      activated prefusion form of PIV5 F. The structure shows minimal movement of the
      residues adjacent to the protease cleavage site. Most of the hydrophobic FP
      residues are buried in the uncleaved F protein, and only F103 at the newly
      created N terminus becomes more solvent-accessible after cleavage. The
      conformational freedom of the charged arginine residues that compose the protease
      recognition site increases on cleavage of F protein.

PMID- 23012474
TI  - Enhanced production of early lineages of monocytic and granulocytic cells in mice
      with colitis.
AB  - The bone marrow (BM) is a large, highly active, and responsive tissue.
      Interestingly, little is known about the impact of colitis on hematopoietic
      functions. Using dextran sodium sulfate (DSS) to induce colitis in mice, we
      identified significant changes in the BM. Specifically, cells of the monocytic
      and granulocytic lineages increased nearly 60% and 80%, respectively. This change
      would support and promote the large infiltration of the gut with neutrophils and
      monocytes that are the primary cause of inflammation and tissue damage during
      colitis. Conversely, the early lineages of B and T cells declined in the marrow
      and thymus with particularly large losses observed among pre-B and pre-T cells
      with heightened levels of apoptosis noted among CD4(+)CD8(+) thymocytes from DSS
      treated mice. Also noteworthy was the 40% decline in cells of the erythrocytic
      lineages in the marrow of colitis mice, which undoubtedly contributed to the
      anemia observed in these mice. The peripheral blood reflected the marrow changes
      as demonstrated by a 2.6-fold increase in neutrophils, a 60% increase in
      monocytes, and a decline in the lymphocyte population. Thus, colitis changed the
      BM in profound ways that parallel the general outcomes of colitis including
      infiltration of the gut with monocytes and neutrophils, inflammation, and anemia.
      The data provide important understandings of the full impact of colitis that may
      lead to unique treatments and therapies.

PMID- 23012475
TI  - Structure of RPE65 isomerase in a lipidic matrix reveals roles for phospholipids
      and iron in catalysis.
AB  - RPE65 is a key metalloenzyme responsible for maintaining visual function in
      vertebrates. Despite extensive research on this membrane-bound retinoid
      isomerase, fundamental questions regarding its enzymology remain unanswered.
      Here, we report the crystal structure of RPE65 in a membrane-like environment.
      These crystals, obtained from enzymatically active, nondelipidated protein,
      displayed an unusual packing arrangement wherein RPE65 is embedded in a lipid
      detergent sheet. Structural differences between delipidated and nondelipidated
      RPE65 uncovered key residues involved in substrate uptake and processing.
      Complementary iron K-edge X-ray absorption spectroscopy data established that
      RPE65 as isolated contained a divalent iron center and demonstrated the presence
      of a tightly bound ligand consistent with a coordinated carboxylate group. These
      results support the hypothesis that the Lewis acidity of iron could be used to
      promote ester dissociation and generation of a carbocation intermediate required
      for retinoid isomerization.

PMID- 23012476
TI  - Pivotal cultural values of nature cannot be integrated into the ecosystem
      services framework.

PMID- 23012477
TI  - Localized cell death focuses mechanical forces during 3D patterning in a biofilm.
AB  - From microbial biofilm communities to multicellular organisms, 3D macroscopic
      structures develop through poorly understood interplay between cellular processes
      and mechanical forces. Investigating wrinkled biofilms of Bacillus subtilis, we
      discovered a pattern of localized cell death that spatially focuses mechanical
      forces, and thereby initiates wrinkle formation. Deletion of genes implicated in
      biofilm development, together with mathematical modeling, revealed that ECM
      production underlies the localization of cell death. Simultaneously with cell
      death, we quantitatively measured mechanical stiffness and movement in WT and
      mutant biofilms. Results suggest that localized cell death provides an outlet for
      lateral compressive forces, thereby promoting vertical mechanical buckling, which
      subsequently leads to wrinkle formation. Guided by these findings, we were able
      to generate artificial wrinkle patterns within biofilms. Formation of 3D
      structures facilitated by cell death may underlie self-organization in other
      developmental systems, and could enable engineering of macroscopic structures
      from cell populations.

PMID- 23012478
TI  - Crystal structures of two subtype N10 neuraminidase-like proteins from bat
      influenza A viruses reveal a diverged putative active site.
AB  - Recently, we reported a unique influenza A virus subtype H17N10 from little
      yellow-shouldered bats. Its neuraminidase (NA) gene encodes a protein that
      appears to be highly divergent from all known influenza NAs and was assigned as a
      new subtype N10. To provide structural and functional insights on the bat H17N10
      virus, X-ray structures were determined for N10 NA proteins from influenza A
      viruses A/little yellow-shouldered bat/Guatemala/164/2009 (GU09-164) in two
      crystal forms at 1.95 A and 2.5 A resolution and A/little yellow-shouldered
      bat/Guatemala/060/2010 (GU10-060) at 2.0 A. The overall N10 structures are
      similar to each other and to other known influenza NA structures, with a single
      highly conserved calcium binding site in each monomer. However, the region
      corresponding to the highly conserved active site of influenza A N1-N9 NA
      subtypes and influenza B NA differs substantially. In particular, most of the
      amino acid residues required for NA activity are substituted, and the putative
      active site is much wider because of displacement of the 150-loop and 430-loop.
      These structural features and the fact that the recombinant N10 protein exhibits
      no, or extremely low, NA activity suggest that it may have a different function
      than the NA proteins of other influenza viruses. Accordingly, we propose that the
      N10 protein be termed an NA-like protein until its function is elucidated.

PMID- 23012479
TI  - Impact of lactobacilli on orally acquired listeriosis.
AB  - Listeria monocytogenes is a foodborne pathogen that crosses the intestinal
      barrier and disseminates within the host. Here, we report a unique comprehensive
      analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM
      I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired
      listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect
      of treatment with each Lactobacillus on L. monocytogenes counts in host tissues
      and showed that each decreases L. monocytogenes systemic dissemination in orally
      inoculated mice. A whole genome intestinal transcriptomic analysis revealed that
      each Lactobacillus changes expression of a specific subset of genes during
      infection, with IFN-stimulated genes (ISGs) being the most affected by both
      lactobacilli. We also examined microRNA (miR) expression and showed that three
      miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes
      infection. Treatment with each Lactobacillus increased miR-192 expression,
      whereas only L. casei association increased miR-200b and miR-215 expression.
      Finally, we showed that treatment with each Lactobacillus significantly reshaped
      the L. monocytogenes transcriptome and up-regulated transcription of L.
      monocytogenes genes encoding enzymes allowing utilization of intestinal carbon
      and nitrogen sources in particular genes involved in propanediol and ethanolamine
      catabolism and cobalamin biosynthesis. Altogether, these data reveal that the
      modulation of L. monocytogenes infection by treatment with lactobacilli
      correlates with a decrease in host gene expression, in particular ISGs, miR
      regulation, and a dramatic reshaping of L. monocytogenes transcriptome.

PMID- 23012480
TI  - AUF1/hnRNP D is a novel protein partner of the EBER1 noncoding RNA of Epstein
      Barr virus.
AB  - Epstein-Barr virus (EBV)-infected cells express two noncoding RNAs called EBV
      encoded RNA (EBER) 1 and EBER2. Despite their high abundance in the nucleus
      (about 10(6) copies), the molecular function of these noncoding RNAs has remained
      elusive. Here, we report that the insertion into EBER1 of an RNA aptamer that
      binds the bacteriophage MS2 coat protein allows the isolation of EBER1 and
      associated protein partners. By combining MS2-mediated selection with stable
      isotope labeling of amino acids in cell culture (SILAC) and analysis by mass
      spectrometry, we identified AUF1 (AU-rich element binding factor 1)/hnRNP D
      (heterogeneous nuclear ribonucleoprotein D) as an interacting protein of EBER1.
      AUF1 exists as four isoforms generated by alternative splicing and is best known
      for its role in destabilizing mRNAs upon binding to AU-rich elements (AREs) in
      their 3' untranslated region (UTR). Using UV crosslinking, we demonstrate that
      predominantly the p40 isoform of AUF1 interacts with EBER1 in vivo.
      Electrophoretic mobility shift assays show that EBER1 can compete for the binding
      of the AUF1 p40 isoform to ARE-containing RNA. Given the high abundance of EBER1
      in EBV-positive cells, EBER1 may disturb the normal homeostasis between AUF1 and
      ARE-containing mRNAs or compete with other AUF1-interacting targets in cells
      latently infected by EBV.

PMID- 23012482
TI  - The absorbed dose in femur exposed to diagnostic radiography.
AB  - A femur phantom made of wax and a real human bone was used to study the dose
      during radiographical procedures. The depth dose inside the phantom was
      determined using DOSXYZnrc, a Monte Carlo simulation software. The results were
      verified with measurements using TLD-100H. It was found that for 2.5 mm aluminium
      filtered 84-kVp X-rays, the radiation dose in the bone reached 57 % higher than
      the surface dose, i.e. 3.23 mGy as opposed to 2.06 mGy at the surface. The use of
      real bone introduces variations in the bone density in the DOSXYZnrc model,
      resulting in a lower attenuation effect than expected from solid bone tissues.

PMID- 23012481
TI  - Intrinsic flexibility of snRNA hairpin loops facilitates protein binding.
AB  - Stem-loop II of U1 snRNA and Stem-loop IV of U2 snRNA typically have 10 or 11
      nucleotides in their loops. The fluorescent nucleobase 2-aminopurine was used as
      a substitute for the adenines in each loop to probe the local and global
      structures and dynamics of these unusually long loops. Using steady-state and
      time-resolved fluorescence, we find that, while the bases in the loops are
      stacked, they are able to undergo significant local motion on the
      picosecond/nanosecond timescale. In addition, the loops have a global
      conformational change at low temperatures that occurs on the microsecond
      timescale, as determined using laser T-jump experiments. Nucleobase and loop
      motions are present at temperatures far below the melting temperature of the
      hairpin stem, which may facilitate the conformational change required for
      specific protein binding to these RNA loops.

PMID- 23012483
TI  - Fetal cerebral imaging - ultrasound vs. MRI: an update.
AB  - The purpose of this article is to analyze the advantages and limitations of
      prenatal ultrasonography (US) and magnetic resonance imaging (MRI) in the
      evaluation of the fetal brain. These imaging modalities should not be seen as
      competitive but rather as complementary. There are wide variations in the world
      regarding screening policies, technology, skills, and legislation about
      termination of pregnancy, and these variations markedly impact on the way of
      using prenatal imaging. According to the contribution expected from each
      technique and to local working conditions, one should choose the most appropriate
      imaging modality on a case-by-case basis. The advantages and limitations of US
      and MRI in the setting of fetal brain imaging are displayed. Different anatomical
      regions (midline, ventricles, subependymal area, cerebral parenchyma,
      pericerebral space, posterior fossa) and pathological conditions are analyzed and
      illustrated in order to compare the respective contribution of each technique. An
      accurate prenatal diagnosis of cerebral abnormalities is of utmost importance for
      prenatal counseling. 

PMID- 23012484
TI  - Anti-CXCR4 monoclonal antibody conjugated to ultrasmall superparamagnetic iron
      oxide nanoparticles in an application of MR molecular imaging of pancreatic
      cancer cell lines.
AB  - BACKGROUND: Chemokine receptor 4(CXCR4) plays an important role in the potential
      growth of pancreatic tumor and its ability to develop metastasis. Ultrasmall
      superparamagnetic iron oxide (USPIO) nanoparticles offer strong contrast
      enhancing effect for MR imaging of pancreatic tissue. PURPOSE: To establish a
      biomarker-targeted nanoparticulate contrast agent CXCR4-USPIO for pancreatic
      cancer cell MR imaging and to investigate the relationship between in vitro MR T2
      enhancement ratio, DeltaR2 values, and the cellular CXCR4 expression levels.
      MATERIAL AND METHODS: The CXCR4 monoclonal antibody and bovine serum albumin
      (BSA) were bioconjugated with USPIO using carbodiimide. The T2 and T2* values of
      CXCR4-USPIO, BSA-USPIO, and USPIO were evaluated at the same iron concentration
      levels. After incubating four pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC
      1, PANC-1) with CXCR4-USPIO and BSA-USPIO, respectively, changes of T2 values
      were measured with a clinical 1.5-T MRI scanner. Western blot and
      immunofluorescence tests were applied to semi-quantitatively analyze the
      expression levels of CXCR4 in the four cell lines. RESULTS: MR imaging revealed a
      linear correlation between DeltaR2 and DeltaR2* values of CXCR4-USPIO
      nanoparticles and the iron concentrations. The T2 enhancement ratio and DeltaR2
      values of AsPC-1, BxPC-3, CFPAC-1, PANC-1 cell lines in the CXCR4-USPIO group
      exhibited strong correlation with the CXCR4 peptide relative grey values measured
      by western blot (r = 0.976, P = 0.024; r = 0.959, P = 0.041, respectively) and
      the mean fluorescence signal intensity detected by laser scanning confocal
      microscopy (r = 0.996, P = 0.004; r = 0.962, P = 0.038, respectively).
      CONCLUSION: The targeted probe CXCR4-USPIO was created for MR molecular imaging
      of pancreatic cancer cell lines. The T2 enhancement ratio and DeltaR2 values of
      CXCR4-USPIO nanoparticles could semi-quantitatively assess the cellular CXCR4
      expression levels.

PMID- 23012485
TI  - Religious Doubts and Sleep Quality: Findings from a Nationwide Study of
      Presbyterians.
AB  - A growing literature examines the correlates and sequelae of spiritual struggles,
      such as religious doubts. To date, however, this literature has focused primarily
      on a handful of mental health outcomes (e.g., symptoms of depression, anxiety,
      negative affect), while the possible links with other aspects of health and well
      being, such as poor or disrupted sleep, have received much less attention. After
      reviewing relevant theory and previous studies, we analyze data from a nationwide
      sample of Presbyterian Church (USA) members to test the hypothesis that religious
      doubts will be inversely associated with overall self-rated sleep quality, and
      positively associated with the frequency of sleep problems and the use of sleep
      medications. We also hypothesize that part of this association will be explained
      by the link between religious doubts and psychological distress. Results offer
      moderate but consistent support for these predictions. We end with a discussion
      of the implications of these findings, a brief mention of study limitations, and
      some suggestions for future research.

PMID- 23012486
TI  - Expression and localization of brain-derived neurotrophic factor (BDNF) mRNA and
      protein in human submandibular gland.
AB  - Brain-derived neurotrophic factor (BDNF) promotes cell survival and
      differentiation in the central and peripheral nervous systems. Previously, we
      reported that BDNF is produced by salivary glands under acute immobilization
      stress in rats. However, expression of BDNF is poorly understood in humans,
      although salivary gland localization of BDNF in rodents has been demonstrated. In
      the present study, we investigated the expression and localization of BDNF in the
      human submandibular gland (HSG) using reverse transcription-polymerase chain
      reaction, western blot analysis, in situ hybridization (ISH),
      immunohistochemistry (IHC), and ELISA. BDNF was consistently localized in HSG
      serous and ductal cells, as detected by ISH and IHC, with reactivity being
      stronger in serous cells. In addition, immunoreactivity for BDNF was observed in
      the saliva matrix of ductal cavities. Western blotting detected one significant
      immunoreactive 14 kDa band in the HSG and saliva. Immunoreactivities for salivary
      BDNF measured by ELISA in humans were 40.76+/-4.83 pg/mL and 52.64+/-8.42 pg/mL,
      in men and women, respectively. Although salivary BDNF concentrations in females
      tended to be higher than in males, the concentrations were not significantly
      different. In conclusion, human salivary BDNF may originate from salivary glands,
      as the HSG appears to produce BDNF.

PMID- 23012487
TI  - Activation of Anterior Cingulate Cortex Extracellular Signal-Regulated Kinase-1
      and -2 (ERK1/2) Regulates Acetic Acid-Induced, Pain-Related Anxiety in Adult
      Female Mice.
AB  - In visceral pain, anxiety and pain occur simultaneously, but the etiogenesis of
      this effect is not yet well-described. The anterior cingulate cortex (ACC) is
      known to be associated with the affective response to noxious stimuli. The aim of
      the current study is to define the role of ACC extracellular signal-regulated
      (ERK)-1 and-2 (ERK1/2) activity in the development of pain-related
      anxiety/depression and the nocifensive response in acetic acid (AA)-elicited
      visceral pain. The model of visceral pain was created by intraperitoneal (ip)
      injection of AA to female Kunming mice. We found that AA injection resulted in a
      dynamic, bilateral ERK1/2 activation pattern in the ACC. Inhibition of ERK1/2
      activation 2 hr after AA injection by subcutaneous (sc) injection of the mitogen
      activating extracellular kinase (MEK) inhibitor, SL327, had no effect on the
      nocifensive responses, but did attenuate anxiety-like behavior, as determined by
      elevated plus-maze and open-field testing results. These data suggest that AA
      induced visceral pain activates expression of ACC ERK1/2, which regulates
      visceral pain-related anxiety, but not the nocifensive response.

PMID- 23012491
TI  - What are the implications of devolved UK healthcare for British specialty
      associations?

PMID- 23012488
TI  - Immunohistochemical Examination of Novel Rat Monoclonal Antibodies against Mouse
      and Human Podoplanin.
AB  - This study aims to develop new monoclonal antibodies (mAbs) against mouse and
      human podoplanin. Rats were immunized with synthetic peptides, corresponding to
      amino acids 38-51 of mouse podoplanin or human podoplanin which is 100%
      homologous to the same site of monkey podoplanin; anti-mouse podoplanin mAb PMab
      1 (IgG(2) (a)) and anti-human mAb NZ-1.2 (IgG(2) (a)) were established. In
      immunocytochemistry, the mouse melanoma B16-F10 and mouse podoplanin (mPDPN)
      expressed CHO transfectant were stained by PMab-1; human lymphatic endothelial
      cells (LEC) and human podoplanin (hPDPN)-expressed squamous cell carcinoma HSC3
      transfectant, were stained by NZ-1.2. Western-blot analysis detected an about 40
      kDa protein in CHO-mPDPN and B16-F10 by PMab-1, and in HSC3-hPDPN and LEC by NZ
      1.2. In frozen sections, PMab-1 reacted with mouse kidney, pulmonary alveoli,
      pulmonary pleura, and salivary gland myoepithelial cells while NZ-1.2 reacted to
      the human salivary gland myoepithelial cells. The immunostaining of paraffin
      embedded sections also showed the reaction of PMab-1 or NZ-1.2 to the mouse or
      monkey kidney glomerulus, pulmonary alveoli, and lung lymphatic vessels. These
      results indicate that the two novel rat mAbs to the mouse and human/monkey
      podoplanin are useful for Western-blot and immunostaining of somatic tissues on
      paraffin-embedded sections as well as frozen sections.

PMID- 23012492
TI  - Respondent driven sampling--where we are and where should we be going?

PMID- 23012494
TI  - Pre-exposure prophylaxis: increasing evidence for effectiveness but should the
      perspective return to test and treat?

PMID- 23012495
TI  - Serological investigation of the collagen degradation profile of patients with
      chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis.
AB  - In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary
      fibrosis (IPF), abnormally high collagen remodeling occurs within the lung
      tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI
      collagen and a disintegrin and metalloproteinase with thrombospondin motifs
      (ADAMTS)-degraded type III collagen were assessed in serum of patients diagnosed
      with mild COPD (n = 10) or IPF (n = 30), and healthy controls (n = 15). The
      collagen degradation markers C1M, C3M, C5M and C6M were significantly elevated in
      serum of both mild COPD and IPF patients, versus controls. C3A and C4M were only
      elevated in patients with mild COPD, compared with controls. The most reliable
      indicators of mild COPD versus controls were: C1M (area under the receiver
      operating characteristics (AUROC = 0.94, P < 0.0001), C3M (AUROC = 0.95, P <
      0.0001), and C5M (AUROC = 0.95, P < 0.0001). The most reliable markers for the
      diagnosis of IPF were achieved by C1M (AUROC = 0.90, P < 0.0001) and C3M (AUROC =
      0.93, P < 0.0001). Collagen degradation was highly up-regulated in patients with
      IPF and mild COPD, indicating that degradation fragments of collagens are
      potential markers of pulmonary diseases. Interestingly, C4M and C3A were only
      elevated in patients with mild COPD, indicating that these markers could be used
      to distinguish between the two pathologies.

PMID- 23012496
TI  - The core mouse response to infection by neospora caninum defined by gene set
      enrichment analyses.
AB  - In this study, the BALB/c and Qs mouse responses to infection by the parasite
      Neospora caninum were investigated in order to identify host response mechanisms.
      Investigation was done using gene set (enrichment) analyses of microarray data.
      GSEA, MANOVA, Romer, subGSE and SAM-GS were used to study the contrasts Neospora
      strain type, Mouse type (BALB/c and Qs) and time post infection (6 hours post
      infection and 10 days post infection). The analyses show that the major signal in
      the core mouse response to infection is from time post infection and can be
      defined by gene ontology terms Protein Kinase Activity, Cell Proliferation and
      Transcription Initiation. Several terms linked to signaling, morphogenesis,
      response and fat metabolism were also identified. At 10 days post infection,
      genes associated with fatty acid metabolism were identified as up regulated in
      expression. The value of gene set (enrichment) analyses in the analysis of
      microarray data is discussed.

PMID- 23012497
TI  - Oscillation of clock and clock controlled genes induced by serum shock in human
      breast epithelial and breast cancer cells: regulation by melatonin.
AB  - This study investigates differences in expression of clock and clock-controlled
      genes (CCGs) between human breast epithelial and breast cancer cells and breast
      tumor xenografts in circadian intact rats and examines if the pineal hormone
      melatonin influences clock gene and CCG expression. Oscillation of clock gene
      expression was not observed under standard growth conditions in vitro, however,
      serum shock (50% horse serum for 2 h) induced oscillation of clock gene and CCG
      expression in MCF-10A cells, which was repressed or disrupted in MCF-7 cells.
      Melatonin administration following serum shock differentially suppressed or
      induced clock gene (Bmal1 and Per2) and CCG expression in MCF10A and MCF-7 cells.
      These studies demonstrate the lack of rhythmic expression of clock genes and CCGs
      of cells in vitro and that transplantation of breast cancer cells as xenografts
      into circadian competent hosts re-establishes a circadian rhythm in the
      peripheral clock genes of tumor cells.

PMID- 23012498
TI  - Half-metallic properties of single-walled polymeric manganese phthalocyanine
      nanotubes.
AB  - We present a theoretical study of the electronic and magnetic properties of
      single-walled manganese phthalocyanine (MnPc) nanotubes which can be thought of
      as rolled-up ribbons of the two-dimensional (2D) polymeric MnPc sheet. Our
      density functional theory calculations show that all of the MnPc nanotubes
      investigated here are half-metals with 100% spin polarization around the Fermi
      level. Following the increase of the tube diameter, the number of spin-down
      energy bands of MnPc nanotubes is always increased while the spin-up band gap of
      MnPc nanotubes approaches that of the 2D MnPc sheet in an oscillatory manner.
      Because the half-metallic character of MnPc nanotubes is deeply rooted in the
      distribution of electrons in the energy bands dominated by the Mn 3d atomic
      orbitals, adsorption of CO molecules on the Mn ions leads to a redistribution of
      electrons in the Mn 3d orbitals and thus can tune precisely the spin state and
      electronic transport properties of MnPc nanotubes, demonstrating promising
      applications of MnPc nanotubes in future molecular spintronics and single
      molecule sensors.

PMID- 23012499
TI  - Detecting service chains and feature interactions in sensor-driven home network
      services.
AB  - Sensor-driven services often cause chain reactions, since one service may
      generate an environmental impact that automatically triggers another service. We
      first propose a framework that can formalize and detect such service chains based
      on ECA (event, condition, action) rules. Although the service chain can be a
      major source of feature interactions, not all service chains lead to harmful
      interactions. Therefore, we then propose a method that identifies feature
      interactions within the service chains. Specifically, we characterize the degree
      of deviation of every service chain by evaluating the gap between expected and
      actual service states. An experimental evaluation demonstrates that the proposed
      method successfully detects 11 service chains and 6 feature interactions within 7
      practical sensor-driven services.

PMID- 23012500
TI  - Development of an automatic approaching system for electrochemical
      nanofabrication using visual and force-displacement sensing.
AB  - In this paper, a fast automatic precision approaching system is developed for
      electrochemical nanofabrication using visual and force-displacement sensing.
      Before the substrate is fabricated, the template should approach the substrate
      accurately to establish the initial gap between the template and substrate.
      During the approaching process, the template is first quickly moved towards the
      substrate by the stepping motor until a specified gap is detected by the visual
      feedback. Then, the successive approach using the switch of macro-micro motion
      with a force-displacement sensing module is triggered to make the template
      contact with the substrate to nanometre accuracy. The contact force is measured
      by the force-displacement sensing module which employs the high-resolution
      capacitive displacement sensor and flexure compliant mechanism. The high
      sensitivity of this capacitive displacement sensor ensures high accuracy of the
      template-substrate contact. The experimental results show that the template can
      reach the substrate accurately and smoothly, which verifies the effectiveness of
      the proposed approaching system with the visual and the force-displacement
      sensing modules.

PMID- 23012502
TI  - Variable-State-Dimension Kalman-based Filter for orientation determination using
      inertial and magnetic sensors.
AB  - In this paper a quaternion-based Variable-State-Dimension Extended Kalman Filter
      (VSD-EKF) is developed for estimating the three-dimensional orientation of a
      rigid body using the measurements from an Inertial Measurement Unit (IMU)
      integrated with a triaxial magnetic sensor. Gyro bias and magnetic disturbances
      are modeled and compensated by including them in the filter state vector. The VSD
      EKF switches between a quiescent EKF, where the magnetic disturbance is modeled
      as a first-order Gauss-Markov stochastic process (GM-1), and a higher-order EKF
      where extra state components are introduced to model the time-rate of change of
      the magnetic field as a GM-1 stochastic process, namely the magnetic disturbance
      is modeled as a second-order Gauss-Markov stochastic process (GM-2). Experimental
      validation tests show the effectiveness of the VSD-EKF, as compared to either the
      quiescent EKF or the higher-order EKF when they run separately.

PMID- 23012503
TI  - Step length estimation using handheld inertial sensors.
AB  - In this paper a novel step length model using a handheld Micro Electrical
      Mechanical System (MEMS) is presented. It combines the user's step frequency and
      height with a set of three parameters for estimating step length. The model has
      been developed and trained using 12 different subjects: six men and six women.
      For reliable estimation of the step frequency with a handheld device, the
      frequency content of the handheld sensor's signal is extracted by applying the
      Short Time Fourier Transform (STFT) independently from the step detection
      process. The relationship between step and hand frequencies is analyzed for
      different hand's motions and sensor carrying modes. For this purpose, the
      frequency content of synchronized signals collected with two sensors placed in
      the hand and on the foot of a pedestrian has been extracted. Performance of the
      proposed step length model is assessed with several field tests involving 10 test
      subjects different from the above 12. The percentages of error over the travelled
      distance using universal parameters and a set of parameters calibrated for each
      subject are compared. The fitted solutions show an error between 2.5 and 5% of
      the travelled distance, which is comparable with that achieved by models proposed
      in the literature for body fixed sensors only.

PMID- 23012501
TI  - Development of a novel optical biosensor for detection of organophosphorus
      pesticides based on methyl parathion hydrolase immobilized by metal-chelate
      affinity.
AB  - We have developed a novel optical biosensor device using recombinant methyl
      parathion hydrolase (MPH) enzyme immobilized on agarose by metal-chelate affinity
      to detect organophosphorus (OP) compounds with a nitrophenyl group. The biosensor
      principle is based on the optical measurement of the product of OP catalysis by
      MPH (p-nitrophenol). Briefly, MPH containing six sequential histidines (6 * His
      tag) at its N-terminal was bound to nitrilotriacetic acid (NTA) agarose with Ni
      ions, resulting in the flexible immobilization of the bio-reaction platform. The
      optical biosensing system consisted of two light-emitting diodes (LEDs) and one
      photodiode. The LED that emitted light at the wavelength of the maximum
      absorption for p-nitrophenol served as the signal light, while the other LED that
      showed no absorbance served as the reference light. The optical sensing system
      detected absorbance that was linearly correlated to methyl parathion (MP)
      concentration and the detection limit was estimated to be 4 MUM. Sensor
      hysteresis was investigated and the results showed that at lower concentration
      range of MP the difference got from the opposite process curves was very small.
      With its easy immobilization of enzymes and simple design in structure, the
      system has the potential for development into a practical portable detector for
      field applications.

PMID- 23012504
TI  - Analysis and design of a speed and position system for maglev vehicles.
AB  - This paper mainly researches one method of speed and location detection for
      maglev vehicles. As the maglev train doesn't have any physical contact with the
      rails, it has to use non-contact measuring methods. The technology based on the
      inductive loop-cable could fulfill the requirement by using an on-board antenna
      which could detect the alternating magnetic field produced by the loop-cable on
      rails. This paper introduces the structure of a speed and position system, and
      analyses the electromagnetic field produced by the loop-cable. The equivalent
      model of the loop-cable is given and the most suitable component of the magnetic
      flux density is selected. Then the paper also compares the alternating current
      (AC) resistance and the quality factor between two kinds of coils which the
      antenna is composed of. The effect of the rails to the signal receiving is also
      researched and then the structure of the coils is improved. Finally, considering
      the common-mode interference, 8-word coils are designed and analyzed.

PMID- 23012505
TI  - Configuring a context-aware middleware for Wireless Sensor Networks.
AB  - In the Future Internet, applications based on Wireless Sensor Networks will have
      to support reconfiguration with minimum human intervention, depending on dynamic
      context changes in their environment. These situations create a need for building
      these applications as adaptive software and including techniques that allow the
      context acquisition and decisions about adaptation. However, contexts use to be
      made up of complex information acquired from heterogeneous devices and user
      characteristics, making them difficult to manage. So, instead of building context
      aware applications from scratch, we propose to use FamiWare, a family of
      middleware for Ambient Intelligence specifically designed to be aware of contexts
      in sensor and smartphone devices. It provides both, several monitoring services
      to acquire contexts from devices and users, and a context-awareness service to
      analyze and detect context changes. However, the current version of FamiWare does
      not allow the automatic incorporation related to the management of new contexts
      into the FamiWare family. To overcome this shortcoming, in this work, we first
      present how to model the context using a metamodel to define the contexts that
      must to be taken into account in an instantiation of FamiWare for a certain
      Ambient Intelligence system. Then, to configure a new context-aware version of
      FamiWare and to generate code ready-to-install within heterogeneous devices, we
      define a mapping that automatically transforms metamodel elements defining
      contexts into elements of the FamiWare family, and we also use the FamiWare
      configuration process to customize the new context-aware variant. Finally, we
      evaluate the benefits of our process, and we analyze both that the new version of
      the middleware works as expected and that it manages the contexts in an efficient
      way.

PMID- 23012506
TI  - Supplying the power requirements to a sensor network using radio frequency power
      transfer.
AB  - Wireless power transmission is a method of supplying power to small electronic
      devices when there is no wired connection. One way to increase the range of these
      systems is to use a directional transmitting antenna, the problem with this
      approach is that power can only be transmitted through a narrow beam and directly
      forward, requiring the transmitter to always be aligned with the sensor node
      position. The work outlined in this article describes the design and testing of
      an autonomous radio frequency power transfer system that is capable of rotating
      the base transmitter to track the position of sensor nodes and transferring power
      to that sensor node. The system's base station monitors the node's energy levels
      and forms a charge queue to plan charging order and maintain energy levels of the
      nodes. Results show a radio frequency harvesting circuit with a measured S11
      value of -31.5 dB and a conversion efficiency of 39.1%. Simulation and
      experimentation verified the level of power transfer and efficiency. The results
      of this work show a small network of three nodes with different storage types
      powered by a central base node.

PMID- 23012507
TI  - Embedded adaptive optics for ubiquitous lab-on-a-chip readout on intact cell
      phones.
AB  - The evaluation of disposable lab-on-a-chip (LOC) devices on cell phones is an
      attractive alternative to migrate the analytical strength of LOC solutions to
      decentralized sensing applications. Imaging the micrometric detection areas of
      LOCs in contact with intact phone cameras is central to provide such capability.
      This work demonstrates a disposable and morphing liquid lens concept that can be
      integrated in LOC devices and refocuses micrometric features in the range
      necessary for LOC evaluation using diverse cell phone cameras. During natural
      evaporation, the lens focus varies adapting to different type of cameras.
      Standard software in the phone commands a time-lapse acquisition for best focal
      selection that is sufficient to capture and resolve, under ambient illumination,
      50 MUm features in regions larger than 500 * 500 MUm(2). In this way, the present
      concept introduces a generic solution compatible with the use of diverse and
      unmodified cell phone cameras to evaluate disposable LOC devices.

PMID- 23012508
TI  - Recent progress in distributed fiber optic sensors.
AB  - Rayleigh, Brillouin and Raman scatterings in fibers result from the interaction
      of photons with local material characteristic features like density, temperature
      and strain. For example an acoustic/mechanical wave generates a dynamic density
      variation; such a variation may be affected by local temperature, strain,
      vibration and birefringence. By detecting changes in the amplitude, frequency and
      phase of light scattered along a fiber, one can realize a distributed fiber
      sensor for measuring localized temperature, strain, vibration and birefringence
      over lengths ranging from meters to one hundred kilometers. Such a measurement
      can be made in the time domain or frequency domain to resolve location
      information. With coherent detection of the scattered light one can observe
      changes in birefringence and beat length for fibers and devices. The progress on
      state of the art technology for sensing performance, in terms of spatial
      resolution and limitations on sensing length is reviewed. These distributed
      sensors can be used for disaster prevention in the civil structural monitoring of
      pipelines, bridges, dams and railroads. A sensor with centimeter spatial
      resolution and high precision measurement of temperature, strain, vibration and
      birefringence can find applications in aerospace smart structures, material
      processing, and the characterization of optical materials and devices.

PMID- 23012509
TI  - Spatial uncertainty model for visual features using a KinectTM sensor.
AB  - This study proposes a mathematical uncertainty model for the spatial measurement
      of visual features using KinectTM sensors. This model can provide qualitative and
      quantitative analysis for the utilization of KinectTM sensors as 3D perception
      sensors. In order to achieve this objective, we derived the propagation
      relationship of the uncertainties between the disparity image space and the real
      Cartesian space with the mapping function between the two spaces. Using this
      propagation relationship, we obtained the mathematical model for the covariance
      matrix of the measurement error, which represents the uncertainty for spatial
      position of visual features from KinectTM sensors. In order to derive the
      quantitative model of spatial uncertainty for visual features, we estimated the
      covariance matrix in the disparity image space using collected visual feature
      data. Further, we computed the spatial uncertainty information by applying the
      covariance matrix in the disparity image space and the calibrated sensor
      parameters to the proposed mathematical model. This spatial uncertainty model was
      verified by comparing the uncertainty ellipsoids for spatial covariance matrices
      and the distribution of scattered matching visual features. We expect that this
      spatial uncertainty model and its analyses will be useful in various KinectTM
      sensor applications.

PMID- 23012510
TI  - A compact annular ring microstrip antenna for WSN applications.
AB  - A compact annular ring microstrip antenna was proposed for a wireless sensor
      network (WSN) application in the 2.4 GHz band. In this paper the major
      considerations of the conformal antenna design were the compact size and the
      impact on antenna's performance of a steel installation base. By using a chip
      resistor of large resistance (120 Omega) the antenna size was reduced to 38% of
      that a conventional annular ring patch antenna. With the addition of the steel
      installation base the resonant frequency of the antenna increases about 4.2% and
      the bandwidth reduces from 17.5% to 11.7% by adjusting the load resistance
      simultaneously. Several key parameters were discussed and optimized, and the
      antenna was fabricated and its performance measured. The antenna is well matched
      at 2.4 GHz with 34.2 dB return loss and -2.5 dBi peak gain. Meanwhile, it
      exhibits excellent radiation patterns with very low cross-polarization levels.

PMID- 23012511
TI  - WebTag: Web browsing into sensor tags over NFC.
AB  - Information and Communication Technologies (ICTs) continue to overcome many of
      the challenges related to wireless sensor monitoring, such as for example the
      design of smarter embedded processors, the improvement of the network
      architectures, the development of efficient communication protocols or the
      maximization of the life cycle autonomy. This work tries to improve the
      communication link of the data transmission in wireless sensor monitoring. The
      upstream communication link is usually based on standard IP technologies, but the
      downstream side is always masked with the proprietary protocols used for the
      wireless link (like ZigBee, Bluetooth, RFID, etc.). This work presents a novel
      solution (WebTag) for a direct IP based access to a sensor tag over the Near
      Field Communication (NFC) technology for secure applications. WebTag allows a
      direct web access to the sensor tag by means of a standard web browser, it reads
      the sensor data, configures the sampling rate and implements IP based security
      policies. It is, definitely, a new step towards the evolution of the Internet of
      Things paradigm.

PMID- 23012512
TI  - A study of hand back skin texture patterns for personal identification and gender
      classification.
AB  - Human hand back skin texture (HBST) is often consistent for a person and
      distinctive from person to person. In this paper, we study the HBST pattern
      recognition problem with applications to personal identification and gender
      classification. A specially designed system is developed to capture HBST images,
      and an HBST image database was established, which consists of 1,920 images from
      80 persons (160 hands). An efficient texton learning based method is then
      presented to classify the HBST patterns. First, textons are learned in the space
      of filter bank responses from a set of training images using the l(1) 
      minimization based sparse representation (SR) technique. Then, under the SR
      framework, we represent the feature vector at each pixel over the learned
      dictionary to construct a representation coefficient histogram. Finally, the
      coefficient histogram is used as skin texture feature for classification.
      Experiments on personal identification and gender classification are performed by
      using the established HBST database. The results show that HBST can be used to
      assist human identification and gender classification.

PMID- 23012513
TI  - Subtitle synchronization across multiple screens and devices.
AB  - Ambient Intelligence is a new paradigm in which environments are sensitive and
      responsive to the presence of people. This is having an increasing importance in
      multimedia applications, which frequently rely on sensors to provide useful
      information to the user. In this context, multimedia applications must adapt and
      personalize both content and interfaces in order to reach acceptable levels of
      context-specific quality of service for the user, and enable the content to be
      available anywhere and at any time. The next step is to make content available to
      everybody in order to overcome the existing access barriers to content for users
      with specific needs, or else to adapt to different platforms, hence making
      content fully usable and accessible. Appropriate access to video content, for
      instance, is not always possible due to the technical limitations of traditional
      video packaging, transmission and presentation. This restricts the flexibility of
      subtitles and audio-descriptions to be adapted to different devices, contexts and
      users. New Web standards built around HTML5 enable more featured applications
      with better adaptation and personalization facilities, and thus would seem more
      suitable for accessible AmI environments. This work presents a video subtitling
      system that enables the customization, adaptation and synchronization of
      subtitles across different devices and multiple screens. The benefits of HTML5
      applications for building the solution are analyzed along with their current
      platform support. Moreover, examples of the use of the application in three
      different cases are presented. Finally, the user experience of the solution is
      evaluated.

PMID- 23012514
TI  - Method for vibration response simulation and sensor placement optimization of a
      machine tool spindle system with a bearing defect.
AB  - Bearing defects are one of the most important mechanical sources for vibration
      and noise generation in machine tool spindles. In this study, an integrated
      finite element (FE) model is proposed to predict the vibration responses of a
      spindle bearing system with localized bearing defects and then the sensor
      placement for better detection of bearing faults is optimized. A nonlinear
      bearing model is developed based on Jones' bearing theory, while the drawbar,
      shaft and housing are modeled as Timoshenko's beam. The bearing model is then
      integrated into the FE model of drawbar/shaft/housing by assembling equations of
      motion. The Newmark time integration method is used to solve the vibration
      responses numerically. The FE model of the spindle-bearing system was verified by
      conducting dynamic tests. Then, the localized bearing defects were modeled and
      vibration responses generated by the outer ring defect were simulated as an
      illustration. The optimization scheme of the sensor placement was carried out on
      the test spindle. The results proved that, the optimal sensor placement depends
      on the vibration modes under different boundary conditions and the transfer path
      between the excitation and the response.

PMID- 23012516
TI  - Comparisons between membrane, bridge and cantilever miniaturized resistive vacuum
      gauges.
AB  - Using bulk micromachining, meander-shaped resistor elements consisting of 20 nm
      Cr and 200 nm Au were fabricated on 1 MUm thick silicon nitride membranes,
      bridges, and cantilevers. The resistance change as a function of pressure depends
      strongly on the thermal resistance of the two metal lines connecting the heated
      resistor to the silicon bulk (cold junction) and on the thermal resistance of the
      silicon nitride. Relative resistance changes ranging from about 3% (small
      membrane) to 20% (bridge) per mW of input power were obtained when operating the
      devices in constant voltage mode. The pressure where maximum sensitivity of these
      gauges occurs depends on the distance 'd' between the periphery of the heated
      resistor element and the silicon cold junction. Devices with 'd' ranging from 50
      MUm to 1,200 MUm were fabricated. Assuming that pressures can be reliably
      measured above the 10% and below the 90% points of the resistance versus pressure
      curve, the range of these devices is about two orders of magnitude. By
      integrating two devices, one with d = 65 MUm and one with d = 1,200 MUm on the
      same chip and connecting them in series, the range can be increased by about a
      factor of three. By fabricating the cantilever devices so that they curl upon
      release, it will be shown that these devices also exhibit larger range due to
      varying 'd'.

PMID- 23012515
TI  - Using a genetic algorithm as an optimal band selector in the mid and thermal
      infrared (2.5-14 MUm) to discriminate vegetation species.
AB  - Genetic variation between various plant species determines differences in their
      physio-chemical makeup and ultimately in their hyperspectral emissivity
      signatures. The hyperspectral emissivity signatures, on the one hand, account for
      the subtle physio-chemical changes in the vegetation, but on the other hand,
      highlight the problem of high dimensionality. The aim of this paper is to
      investigate the performance of genetic algorithms coupled with the spectral angle
      mapper (SAM) to identify a meaningful subset of wavebands sensitive enough to
      discriminate thirteen broadleaved vegetation species from the laboratory measured
      hyperspectral emissivities. The performance was evaluated using an overall
      classification accuracy and Jeffries Matusita distance. For the multiple plant
      species, the targeted bands based on genetic algorithms resulted in a high
      overall classification accuracy (90%). Concentrating on the pairwise comparison
      results, the selected wavebands based on genetic algorithms resulted in higher
      Jeffries Matusita (J-M) distances than randomly selected wavebands did. This
      study concludes that targeted wavebands from leaf emissivity spectra are able to
      discriminate vegetation species.

PMID- 23012517
TI  - An adaptive OFDMA-based MAC protocol for underwater acoustic wireless sensor
      networks.
AB  - Underwater acoustic wireless sensor networks (UAWSNs) have many applications
      across various civilian and military domains. However, they suffer from the
      limited available bandwidth of acoustic signals and harsh underwater conditions.
      In this work, we present an Orthogonal Frequency Division Multiple Access (OFDMA)
      based Media Access Control (MAC) protocol that is configurable to suit the
      operating requirements of the underwater sensor network. The protocol has three
      modes of operation, namely random, equal opportunity and energy-conscious modes
      of operation. Our MAC design approach exploits the multi-path characteristics of
      a fading acoustic channel to convert it into parallel independent acoustic sub
      channels that undergo flat fading. Communication between node pairs within the
      network is done using subsets of these sub-channels, depending on the
      configurations of the active mode of operation. Thus, the available limited
      bandwidth gets fully utilized while completely avoiding interference. We derive
      the mathematical model for optimal power loading and subcarrier selection, which
      is used as basis for all modes of operation of the protocol. We also conduct many
      simulation experiments to evaluate and compare our protocol with other Code
      Division Multiple Access (CDMA)-based MAC protocols.

PMID- 23012518
TI  - Immobilization of ionophore and surface characterization studies of the
      titanium(III) ion in a PVC-membrane sensor.
AB  - Novel ionophores comprising various hydroxide and amine structures were
      immobilized onto poly(vinyl chloride) (PVC) matrices, and these were examined to
      determine Ti(III) selectivity. To predict the selectivity of Ti(III), a PVC
      membrane was used to investigate the binding of Ti(III) to c
      methylcalix[4]resorcinarene (CMCR). The study showed that the chelating ligand,
      CMCR, was coordinated selectively to Ti(III) at eight coordination sites
      involving the oxygen atoms at the interface of the membrane/solution. The
      membrane was prepared, based on CMCR as an ionophore, sodium tetrakis(4
      fluorophenyl) borate (NaTFPB) as a lipophilic ionic additive, and
      dioctylphthalate (DOP) as a plasticizer. The immobilization of the ionophore and
      surface characterization studies revealed that the performance of CMCR
      immobilized PVC was equivalent to that of mobile ionophores in supported liquid
      membranes (SLMs). The strengths of the ion-ionophore (CMCR-Ti(OH)(OH(2))(5) (2+))
      interactions and the role of ionophores on membranes were studied via UV-Vis,
      Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy
      (SEM) and and X-ray diffraction (XRD).

PMID- 23012519
TI  - Searching dynamic agents with a team of mobile robots.
AB  - This paper presents a new algorithm that allows a team of robots to cooperatively
      search for a set of moving targets. An estimation of the areas of the environment
      that are more likely to hold a target agent is obtained using a grid-based
      Bayesian filter. The robot sensor readings and the maximum speed of the moving
      targets are used in order to update the grid. This representation is used in a
      search algorithm that commands the robots to those areas that are more likely to
      present target agents. This algorithm splits the environment in a tree of
      connected regions using dynamic programming. This tree is used in order to decide
      the destination for each robot in a coordinated manner. The algorithm has been
      successfully tested in known and unknown environments showing the validity of the
      approach.

PMID- 23012521
TI  - Optical fiber relative humidity sensor based on a FBG with a di-ureasil coating.
AB  - In this work we proposed a relative humidity (RH) sensor based on a Bragg grating
      written in an optical fiber, associated with a coating of organo-silica hybrid
      material prepared by the sol-gel method. The organo-silica-based coating has a
      strong adhesion to the optical fiber and its expansion is reversibly affected by
      the change in the RH values (15.0-95.0%) of the surrounding environment, allowing
      an increased sensitivity (22.2 pm/%RH) and durability due to the presence of a
      siliceous-based inorganic component. The developed sensor was tested in a real
      structure health monitoring essay, in which the RH inside two concrete blocks
      with different porosity values was measured over 1 year. The results demonstrated
      the potential of the proposed optical sensor in the monitoring of civil
      engineering structures.

PMID- 23012520
TI  - Biomarkers for use in monitoring responses of nasopharyngeal carcinoma cells to
      ionizing radiation.
AB  - Nasopharyngeal carcinoma (NPC) is a common head and neck cancer. The incidence
      rate is higher in southern China and Southeast Asia in comparison with the
      Western countries. Radiotherapy is the standard treatment of NPC as the cancer
      cells are sensitive to ionizing radiation. Radiation treatment has good local
      control to patients with early NPC. It is essential to monitor the response of
      the NPC cells to radiation treatment in advance in order to select suitable
      treatment choice for the patients. This review aims to discuss the potential use
      of biomarkers in monitoring the responsiveness of NPC cells to radiation
      treatment.

PMID- 23012522
TI  - Microfiber-based Bragg gratings for sensing applications: a review.
AB  - Microfiber-based Bragg gratings (MFBGs) are an emerging concept in ultra-small
      optical fiber sensors. They have attracted great attention among researchers in
      the fiber sensing area because of their large evanescent field and compactness.
      In this review, the basic techniques for the fabrication of MFBGs are introduced
      first. Then, the sensing properties and applications of MFBGs are discussed,
      including measurement of refractive index (RI), temperature, and strain/force.
      Finally a summary of selected MFBG sensing elements from previous literature are
      tabulated.

PMID- 23012523
TI  - Observability analysis of a matrix Kalman filter-based navigation system using
      visual/inertial/magnetic sensors.
AB  - A matrix Kalman filter (MKF) has been implemented for an integrated navigation
      system using visual/inertial/magnetic sensors. The MKF rearranges the original
      nonlinear process model in a pseudo-linear process model. We employ the
      observability rank criterion based on Lie derivatives to verify the conditions
      under which the nonlinear system is observable. It has been proved that such
      observability conditions are: (a) at least one degree of rotational freedom is
      excited, and (b) at least two linearly independent horizontal lines and one
      vertical line are observed. Experimental results have validated the correctness
      of these observability conditions.

PMID- 23012524
TI  - An ANN-based smart tomographic reconstructor in a dynamic environment.
AB  - In astronomy, the light emitted by an object travels through the vacuum of space
      and then the turbulent atmosphere before arriving at a ground based telescope. By
      passing through the atmosphere a series of turbulent layers modify the light's
      wave-front in such a way that Adaptive Optics reconstruction techniques are
      needed to improve the image quality. A novel reconstruction technique based in
      Artificial Neural Networks (ANN) is proposed. The network is designed to use the
      local tilts of the wave-front measured by a Shack Hartmann Wave-front Sensor
      (SHWFS) as inputs and estimate the turbulence in terms of Zernike coefficients.
      The ANN used is a Multi-Layer Perceptron (MLP) trained with simulated data with
      one turbulent layer changing in altitude. The reconstructor was tested using
      three different atmospheric profiles and compared with two existing
      reconstruction techniques: Least Squares type Matrix Vector Multiplication (LS)
      and Learn and Apply (L + A).

PMID- 23012525
TI  - Maximum likelihood-based iterated divided difference filter for nonlinear systems
      from discrete noisy measurements.
AB  - A new filter named the maximum likelihood-based iterated divided difference
      filter (MLIDDF) is developed to improve the low state estimation accuracy of
      nonlinear state estimation due to large initial estimation errors and
      nonlinearity of measurement equations. The MLIDDF algorithm is derivative-free
      and implemented only by calculating the functional evaluations. The MLIDDF
      algorithm involves the use of the iteration measurement update and the current
      measurement, and the iteration termination criterion based on maximum likelihood
      is introduced in the measurement update step, so the MLIDDF is guaranteed to
      produce a sequence estimate that moves up the maximum likelihood surface. In a
      simulation, its performance is compared against that of the unscented Kalman
      filter (UKF), divided difference filter (DDF), iterated unscented Kalman filter
      (IUKF) and iterated divided difference filter (IDDF) both using a traditional
      iteration strategy. Simulation results demonstrate that the accumulated mean
      square root error for the MLIDDF algorithm in position is reduced by 63% compared
      to that of UKF and DDF algorithms, and by 7% compared to that of IUKF and IDDF
      algorithms. The new algorithm thus has better state estimation accuracy and a
      fast convergence rate.

PMID- 23012526
TI  - Enabling flexible and continuous capability invocation in mobile prosumer
      environments.
AB  - Mobile prosumer environments require the communication with heterogeneous devices
      during the execution of mobile services. These environments integrate sensors,
      actuators and smart devices, whose availability continuously changes. The aim of
      this paper is to design a reference architecture for implementing a model for
      continuous service execution and access to capabilities, i.e., the
      functionalities provided by these devices. The defined architecture follows a set
      of software engineering patterns and includes some communication paradigms to
      cope with the heterogeneity of sensors, actuators, controllers and other devices
      in the environment. In addition, we stress the importance of the flexibility in
      capability invocation by allowing the communication middleware to select the
      access technology and change the communication paradigm when dealing with smart
      devices, and by describing and evaluating two algorithms for resource access
      management.

PMID- 23012527
TI  - An oxidase-based electrochemical fluidic sensor with high-sensitivity and low
      interference by on-chip oxygen manipulation.
AB  - Utilizing a simple fluidic structure, we demonstrate the improved performance of
      oxidase-based enzymatic biosensors. Electrolysis of water is utilized to generate
      bubbles to manipulate the oxygen microenvironment close to the biosensor in a
      fluidic channel. For the proper enzyme reactions to occur, a simple mechanical
      procedure of manipulating bubbles was developed to maximize the oxygen level
      while minimizing the pH change after electrolysis. The sensors show improved
      sensitivities based on the oxygen dependency of enzyme reaction. In addition,
      this oxygen-rich operation minimizes the ratio of electrochemical interference
      signal by ascorbic acid during sensor operation (i.e., amperometric detection of
      hydrogen peroxide). Although creatinine sensors have been used as the model
      system in this study, this method is applicable to many other biosensors that can
      use oxidase enzymes (e.g., glucose, alcohol, phenol, etc.) to implement a viable
      component for in-line fluidic sensor systems.

PMID- 23012529
TI  - Analysis of building envelope insulation performance utilizing integrated
      temperature and humidity sensors.
AB  - A major cause of high energy consumption for air conditioning in indoor spaces is
      the thermal storage characteristics of a building's envelope concrete material;
      therefore, the physiological signals (temperature and humidity) within concrete
      structures are an important reference for building energy management. The current
      approach to measuring temperature and humidity within concrete structures (i.e.,
      thermocouples and fiber optics) is limited by problems of wiring requirements,
      discontinuous monitoring, and high costs. This study uses radio frequency
      integrated circuits (RFIC) combined with temperature and humidity sensors (T/H
      sensors) for the design of a smart temperature and humidity information material
      (STHIM) that automatically, regularly, and continuously converts temperature and
      humidity signals within concrete and transmits them by radio frequency (RF) to
      the Building Physiology Information System (BPIS). This provides a new approach
      to measurement that incorporates direct measurement, wireless communication, and
      real-time continuous monitoring to assist building designers and users in making
      energy management decisions and judgments.

PMID- 23012528
TI  - Study designs and statistical analyses for biomarker research.
AB  - Biomarkers are becoming increasingly important for streamlining drug discovery
      and development. In addition, biomarkers are widely expected to be used as a tool
      for disease diagnosis, personalized medication, and surrogate endpoints in
      clinical research. In this paper, we highlight several important aspects related
      to study design and statistical analysis for clinical research incorporating
      biomarkers. We describe the typical and current study designs for exploring,
      detecting, and utilizing biomarkers. Furthermore, we introduce statistical issues
      such as confounding and multiplicity for statistical tests in biomarker research.

PMID- 23012530
TI  - Improving the calibration of image sensors based on IOFBs, using differential
      gray-code space encoding.
AB  - This paper presents a fast calibration method to determine the transfer function
      for spatial correspondences in image transmission devices with Incoherent Optical
      Fiber Bundles (IOFBs), by performing a scan of the input, using differential
      patterns generated from a Gray code (Differential Gray-Code Space Encoding,
      DGSE). The results demonstrate that this technique provides a noticeable
      reduction in processing time and better quality of the reconstructed image
      compared to other, previously employed techniques, such as point or fringe
      scanning, or even other known space encoding techniques.

PMID- 23012531
TI  - Semi-blind signal extraction for communication signals by combining independent
      component analysis and spatial constraints.
AB  - Signal of interest (SOI) extraction is a vital issue in communication signal
      processing. In this paper, we propose two novel iterative algorithms for
      extracting SOIs from instantaneous mixtures, which explores the spatial
      constraint corresponding to the Directions of Arrival (DOAs) of the SOIs as a
      priori information into the constrained Independent Component Analysis (cICA)
      framework. The first algorithm utilizes the spatial constraint to form a new
      constrained optimization problem under the previous cICA framework which requires
      various user parameters, i.e., Lagrange parameter and threshold measuring the
      accuracy degree of the spatial constraint, while the second algorithm
      incorporates the spatial constraints to select specific initialization of
      extracting vectors. The major difference between the two novel algorithms is that
      the former incorporates the prior information into the learning process of the
      iterative algorithm and the latter utilizes the prior information to select the
      specific initialization vector. Therefore, no extra parameters are necessary in
      the learning process, which makes the algorithm simpler and more reliable and
      helps to improve the speed of extraction. Meanwhile, the convergence condition
      for the spatial constraints is analyzed. Compared with the conventional
      techniques, i.e., MVDR, numerical simulation results demonstrate the
      effectiveness, robustness and higher performance of the proposed algorithms.

PMID- 23012532
TI  - Analysis of uncertainty and repeatability of a low-cost 3D laser scanner.
AB  - Portable 3D laser scanners are a valuable tool for compiling elaborate digital
      collections of archaeological objects and analysing the shapes and dimensions of
      pieces. Although low-cost desktop 3D laser scanners have powerful capacities, it
      is important to know their limitations. This paper performs an analysis of the
      uncertainty and repeatability of the NextEngineTM portable low-cost 3D laser
      scanner by scanning an object 20 times in two different resolution modes-Macro
      and Wide. Some dimensions of the object were measured using a digital calliper,
      and these results were used as the "true" or control data. In comparing the true
      and the scanned data, we verified that the mean uncertainty in the Macro Mode is
      approximately half that of the Wide Mode, at +/- 0.81 mm and +/- 1.66 mm,
      respectively. These experimental results are significantly higher than the
      accuracy specifications provided by the manufacturer. An analysis of
      repeatability shows that the successive replicates do not match in the same
      position. The results are better in Macro Mode than in Wide Mode; it is observed
      that the repeatability factor is slightly larger than the corresponding mode
      accuracy, with +/- 0.84 vs. +/- 0.81 mm in Macro Mode and +/- 1.82 vs. +/- 1.66
      mm in Wide Mode. We suggest several improvements, such as adding an external
      reference scale or providing a calibrated object to allow for a self-calibration
      operation of the scanner.

PMID- 23012533
TI  - Game theory for Wireless Sensor Networks: a survey.
AB  - Game theory (GT) is a mathematical method that describes the phenomenon of
      conflict and cooperation between intelligent rational decision-makers. In
      particular, the theory has been proven very useful in the design of wireless
      sensor networks (WSNs). This article surveys the recent developments and findings
      of GT, its applications in WSNs, and provides the community a general view of
      this vibrant research area. We first introduce the typical formulation of GT in
      the WSN application domain. The roles of GT are described that include routing
      protocol design, topology control, power control and energy saving, packet
      forwarding, data collection, spectrum allocation, bandwidth allocation, quality
      of service control, coverage optimization, WSN security, and other sensor
      management tasks. Then, three variations of game theory are described, namely,
      the cooperative, non-cooperative, and repeated schemes. Finally, existing
      problems and future trends are identified for researchers and engineers in the
      field.

PMID- 23012534
TI  - Design parameters of a miniaturized piezoelectric underwater acoustic
      transmitter.
AB  - PZT ceramics have been widely used in underwater acoustic transducers. However,
      literature available discussing the design parameters of a miniaturized PZT-based
      low-duty-cycle transmitter is very limited. This paper discusses some of the
      design parameters--the backing material, driving voltage, PZT material type,
      power consumption and the transducer length of a miniaturized acoustic fish tag
      using a PZT tube. Four different types of PZT were evaluated with respect to the
      source level, energy consumption and bandwidth of the transducer. The effect of
      the tube length on the source level is discussed. The results demonstrate that
      ultralow-density closed-cell foam is the best backing material for the PZT tube.
      The Navy Type VI PZTs provide the best source level with relatively low energy
      consumption and that a low transducer capacitance is preferred for high
      efficiency. A 35% reduction in the transducer length results in 2 dB decrease in
      source level.

PMID- 23012535
TI  - Laser scanning on road pavements: a new approach for characterizing surface
      texture.
AB  - The surface layer of road pavement has a particular importance in relation to the
      satisfaction of the primary demands of locomotion, such as security and eco
      compatibility. Among those pavement surface characteristics, the "texture"
      appears to be one of the most interesting with regard to the attainment of skid
      resistance. Specifications and regulations, providing a wide range of functional
      indicators, act as guidelines to satisfy the performance requirements. This paper
      describes an experiment on the use of laser scanner techniques on various types
      of asphalt for texture characterization. The use of high precision laser
      scanners, such as the triangulation types, is proposed to expand the analysis of
      road pavement from the commonly and currently used two-dimensional method to a
      three-dimensional one, with the aim of extending the range of the most important
      parameters for these kinds of applications. Laser scanners can be used in an
      innovative way to obtain information on areal surface layer through a single
      measurement, with data homogeneity and representativeness. The described
      experience highlights how the laser scanner is used for both laboratory
      experiments and tests in situ, with a particular attention paid to factors that
      could potentially affect the survey.

PMID- 23012536
TI  - Performance testing of a magnetically suspended double gimbal control moment gyro
      based on the single axis air bearing table.
AB  - Integrating the advantage of magnetic bearings with a double gimble control
      moment gyroscope (DGCMG), a magnetically suspended DGCMG (MSDGCMG) is an ideal
      actuator in high-precision, long life, and rapid maneuver attitude control
      systems. The work presented here mainly focuses on performance testing of a
      MSDGCMG independently developed by Beihang University, based on the single axis
      air bearing table. In this paper, taking into sufficient consideration to the
      moving-gimbal effects and the response bandwidth limit of the gimbal, a special
      MSDGCMG steering law is proposed subject to the limits of gimbal angle rate and
      angle acceleration. Finally, multiple experiments are carried out, with different
      MSDGCMG angular momenta as well as different desired attitude angles. The
      experimental results indicate that the MSDGCMG has a good gimbal angle rate and
      output torque tracking capabilities, and that the attitude stability with MSDGCMG
      as actuator is superior to 10(-3) degrees /s. The MSDGCMG performance testing in
      this paper, carried out under moving-base condition, will offer a technique base
      for the future research and application of MSDGCMGs.

PMID- 23012538
TI  - The development of an UAV borne direct georeferenced photogrammetric platform for
      Ground Control Point free applications.
AB  - To facilitate applications such as environment detection or disaster monitoring,
      the development of rapid low cost systems for collecting near real time spatial
      information is very critical. Rapid spatial information collection has become an
      emerging trend for remote sensing and mapping applications. In this study, a
      fixed-wing Unmanned Aerial Vehicle (UAV)-based spatial information acquisition
      platform that can operate in Ground Control Point (GCP) free environments is
      developed and evaluated. The proposed UAV based photogrammetric platform has a
      Direct Georeferencing (DG) module that includes a low cost Micro Electro
      Mechanical Systems (MEMS) Inertial Navigation System (INS)/Global Positioning
      System (GPS) integrated system. The DG module is able to provide GPS single
      frequency carrier phase measurements for differential processing to obtain
      sufficient positioning accuracy. All necessary calibration procedures are
      implemented. Ultimately, a flight test is performed to verify the positioning
      accuracy in DG mode without using GCPs. The preliminary results of positioning
      accuracy in DG mode illustrate that horizontal positioning accuracies in the x
      and y axes are around 5 m at 300 m flight height above the ground. The
      positioning accuracy of the z axis is below 10 m. Therefore, the proposed
      platform is relatively safe and inexpensive for collecting critical spatial
      information for urgent response such as disaster relief and assessment
      applications where GCPs are not available.

PMID- 23012537
TI  - Modelling carbon nanotubes-based mediatorless biosensor.
AB  - This paper presents a mathematical model of carbon nanotubes-based mediatorless
      biosensor. The developed model is based on nonlinear non-stationary reaction
      diffusion equations. The model involves four layers (compartments): a layer of
      enzyme solution entrapped on a terylene membrane, a layer of the single walled
      carbon nanotubes deposited on a perforated membrane, and an outer diffusion
      layer. The biosensor response and sensitivity are investigated by changing the
      model parameters with a special emphasis on the mediatorless transfer of the
      electrons in the layer of the enzyme-loaded carbon nanotubes. The numerical
      simulation at transient and steady state conditions was carried out using the
      finite difference technique. The mathematical model and the numerical solution
      were validated by experimental data. The obtained agreement between the
      simulation results and the experimental data was admissible at different
      concentrations of the substrate.

PMID- 23012540
TI  - A reasoning hardware platform for real-time common-sense inference.
AB  - Enabling Ambient Intelligence systems to understand the activities that are
      taking place in a supervised context is a rather complicated task. Moreover, this
      task cannot be successfully addressed while overlooking the mechanisms (common
      sense knowledge and reasoning) that entitle us, as humans beings, to successfully
      undertake it. This work is based on the premise that Ambient Intelligence systems
      will be able to understand and react to context events if common-sense
      capabilities are embodied in them. However, there are some difficulties that need
      to be resolved before common-sense capabilities can be fully deployed to Ambient
      Intelligence. This work presents a hardware accelerated implementation of a
      common-sense knowledge-base system intended to improve response time and
      efficiency.

PMID- 23012539
TI  - A unifying review of bioassay-guided fractionation, effect-directed analysis and
      related techniques.
AB  - The success of modern methods in analytical chemistry sometimes obscures the
      problem that the ever increasing amount of analytical data does not necessarily
      give more insight of practical relevance. As alternative approaches, toxicity-
      and bioactivity-based assays can deliver valuable information about biological
      effects of complex materials in humans, other species or even ecosystems.
      However, the observed effects often cannot be clearly assigned to specific
      chemical compounds. In these cases, the establishment of an unambiguous cause
      effect relationship is not possible. Effect-directed analysis tries to
      interconnect instrumental analytical techniques with a biological/biochemical
      entity, which identifies or isolates substances of biological relevance.
      Successful application has been demonstrated in many fields, either as proof-of
      principle studies or even for complex samples. This review discusses the
      different approaches, advantages and limitations and finally shows some practical
      examples. The broad emergence of effect-directed analytical concepts might lead
      to a true paradigm shift in analytical chemistry, away from ever growing lists of
      chemical compounds. The connection of biological effects with the identification
      and quantification of molecular entities leads to relevant answers to many real
      life questions.

PMID- 23012542
TI  - Using a communication model to collect measurement data through mobile devices.
AB  - Wireless systems and services have undergone remarkable development since the
      first mobile phone system was introduced in the early 1980s. The use of sensors
      in an Ambient Intelligence approach is a great solution in a medical environment.
      We define a communication architecture to facilitate the information transfer
      between all connected devices. This model is based in layers to allow the
      collection of measurement data to be used in our framework monitoring
      architecture. An overlay-based solution is built between network elements in
      order to provide an efficient and highly functional communication platform that
      allows the connection of a wide variety of devices and technologies, and serves
      also to perform additional functions such as the possibility to perform some
      processing in the network that may help to improve overall performance.

PMID- 23012541
TI  - Microarray technology for major chemical contaminants analysis in food: current
      status and prospects.
AB  - Chemical contaminants in food have caused serious health issues in both humans
      and animals. Microarray technology is an advanced technique suitable for the
      analysis of chemical contaminates. In particular, immuno-microarray approach is
      one of the most promising methods for chemical contaminants analysis. The use of
      microarrays for the analysis of chemical contaminants is the subject of this
      review. Fabrication strategies and detection methods for chemical contaminants
      are discussed in detail. Application to the analysis of mycotoxins, biotoxins,
      pesticide residues, and pharmaceutical residues is also described. Finally,
      future challenges and opportunities are discussed.

PMID- 23012543
TI  - Laser scanning measurements on trees for logging harvesting operations.
AB  - Logging harvesters represent a set of high-performance modern forestry machinery,
      which can finish a series of continuous operations such as felling, delimbing,
      peeling, bucking and so forth with human intervention. It is found by experiment
      that during the process of the alignment of the harvesting head to capture the
      trunk, the operator needs a lot of observation, judgment and repeated operations,
      which lead to the time and fuel losses. In order to improve the operation
      efficiency and reduce the operating costs, the point clouds for standing trees
      are collected with a low-cost 2D laser scanner. A cluster extracting algorithm
      and filtering algorithm are used to classify each trunk from the point cloud. On
      the assumption that every cross section of the target trunk is approximate a
      standard circle and combining the information of an Attitude and Heading
      Reference System, the radii and center locations of the trunks in the scanning
      range are calculated by the Fletcher-Reeves conjugate gradient algorithm. The
      method is validated through experiments in an aspen forest, and the optimized
      calculation time consumption is compared with the previous work of other
      researchers. Moreover, the implementation of the calculation result for
      automotive capturing trunks by the harvesting head during the logging operation
      is discussed in particular.

PMID- 23012544
TI  - Model-driven methodology for rapid deployment of smart spaces based on resource
      oriented architectures.
AB  - Advances in electronics nowadays facilitate the design of smart spaces based on
      physical mash-ups of sensor and actuator devices. At the same time, software
      paradigms such as Internet of Things (IoT) and Web of Things (WoT) are motivating
      the creation of technology to support the development and deployment of web
      enabled embedded sensor and actuator devices with two major objectives: (i) to
      integrate sensing and actuating functionalities into everyday objects, and (ii)
      to easily allow a diversity of devices to plug into the Internet. Currently,
      developers who are applying this Internet-oriented approach need to have solid
      understanding about specific platforms and web technologies. In order to
      alleviate this development process, this research proposes a Resource-Oriented
      and Ontology-Driven Development (ROOD) methodology based on the Model Driven
      Architecture (MDA). This methodology aims at enabling the development of smart
      spaces through a set of modeling tools and semantic technologies that support the
      definition of the smart space and the automatic generation of code at hardware
      level. ROOD feasibility is demonstrated by building an adaptive health monitoring
      service for a Smart Gym.

PMID- 23012545
TI  - SGA-WZ: a new strapdown airborne gravimeter.
AB  - Inertial navigation systems and gravimeters are now routinely used to map the
      regional gravitational quantities from an aircraft with mGal accuracy and a
      spatial resolution of a few kilometers. However, airborne gravimeter of this kind
      is limited by the inaccuracy of the inertial sensor performance, the integrated
      navigation technique and the kinematic acceleration determination. As the GPS
      technique developed, the vehicle acceleration determination is no longer the
      limiting factor in airborne gravity due to the cancellation of the common mode
      acceleration in differential mode. A new airborne gravimeter taking full
      advantage of the inertial navigation system is described with improved mechanical
      design, high precision time synchronization, better thermal control and optimized
      sensor modeling. Apart from the general usage, the Global Positioning System
      (GPS) after differentiation is integrated to the inertial navigation system which
      provides not only more precise altitude information along with the navigation
      aiding, but also an effective way to calculate the vehicle acceleration. Design
      description and test results on the performance of the gyroscopes and
      accelerations will be emphasized. Analysis and discussion of the airborne field
      test results are also given.

PMID- 23012547
TI  - Investigating the quantitative structure-activity relationships for antibody
      recognition of two immunoassays for polycyclic aromatic hydrocarbons by multiple
      regression methods.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants found in the
      environment. Immunoassays represent useful analytical methods to complement
      traditional analytical procedures for PAHs. Cross-reactivity (CR) is a very
      useful character to evaluate the extent of cross-reaction of a cross-reactant in
      immunoreactions and immunoassays. The quantitative relationships between the
      molecular properties and the CR of PAHs were established by stepwise multiple
      linear regression, principal component regression and partial least square
      regression, using the data of two commercial enzyme-linked immunosorbent assay
      (ELISA) kits. The objective is to find the most important molecular properties
      that affect the CR, and predict the CR by multiple regression methods. The
      results show that the physicochemical, electronic and topological properties of
      the PAH molecules have an integrated effect on the CR properties for the two
      ELISAs, among which molar solubility (S(m)) and valence molecular connectivity
      index ((3)chi(v)) are the most important factors. The obtained regression
      equations for Ris(C) kit are all statistically significant (p < 0.005) and show
      satisfactory ability for predicting CR values, while equations for RaPID kit are
      all not significant (p > 0.05) and not suitable for predicting. It is probably
      because that the Ris(C) immunoassay employs a monoclonal antibody, while the
      RaPID kit is based on polyclonal antibody. Considering the important effect of
      solubility on the CR values, cross-reaction potential (CRP) is calculated and
      used as a complement of CR for evaluation of cross-reactions in immunoassays.
      Only the compounds with both high CR and high CRP can cause intense cross
      reactions in immunoassays.

PMID- 23012546
TI  - Circulating microRNAs: molecular microsensors in gastrointestinal cancer.
AB  - MicroRNAs (miRNAs) are small molecules of single strand non-coding RNAs, which
      are able to regulate gene expression. miRNAs have been involved in multiple
      cellular processes, such as proliferation, apoptosis and differentiation, thus
      alterations in miRNA expression have been shown to be directly linked with the
      pathological origin of multiple diseases, including cancer. In this way, during
      last few years, an increasing number of exciting advances have contributed to the
      understanding of miRNA roles in cancer. Moreover, researchers have exploited the
      special characteristics of miRNAs, such as the tissue and disease specificity or
      miRNA presence in blood, to explore their use as non-invasive tumour markers. In
      the present review, we summarize the current data on the potential usefulness of
      circulating miRNAs as diagnostic and prognostic tools in gastrointestinal
      tumours.

PMID- 23012549
TI  - AUV SLAM and experiments using a mechanical scanning forward-looking sonar.
AB  - Navigation technology is one of the most important challenges in the applications
      of autonomous underwater vehicles (AUVs) which navigate in the complex undersea
      environment. The ability of localizing a robot and accurately mapping its
      surroundings simultaneously, namely the simultaneous localization and mapping
      (SLAM) problem, is a key prerequisite of truly autonomous robots. In this paper,
      a modified-FastSLAM algorithm is proposed and used in the navigation for our C
      Ranger research platform, an open-frame AUV. A mechanical scanning imaging sonar
      is chosen as the active sensor for the AUV. The modified-FastSLAM implements the
      update relying on the on-board sensors of C-Ranger. On the other hand, the
      algorithm employs the data association which combines the single particle maximum
      likelihood method with modified negative evidence method, and uses the rank-based
      resampling to overcome the particle depletion problem. In order to verify the
      feasibility of the proposed methods, both simulation experiments and sea trials
      for C-Ranger are conducted. The experimental results show the modified-FastSLAM
      employed for the navigation of the C-Ranger AUV is much more effective and
      accurate compared with the traditional methods.

PMID- 23012548
TI  - Effect of plasma treatment on multi-walled carbon nanotubes for the detection of
      H2S and SO2.
AB  - H(2)S and SO(2) are important characteristic gases of partial discharge (PD)
      generated by latent insulated defects in gas insulated switchgear (GIS). The
      detection of H(2)S and SO(2) is of great significance in the diagnosis and
      assessment of the operating status of GIS. In this paper, we perform experiments
      on the gas sensitivity of unmodified multi-walled carbon nanotubes (MWNTs) and
      those modified by atmospheric pressure dielectric barrier discharge (DBD) air
      plasma at different times (30, 60 and 120 s) for H(2)S and SO(2), respectively.
      The results show that the sensitivity and response time of modified MWNTs to
      H(2)S are both improved, whereas the opposite effects are observed for SO(2). The
      modified MWNTs have almost zero sensitivity to SO(2). Thus, the MWNTs modified by
      atmospheric pressure DBD air plasma present good selectivity to H(2)S, and have
      great potential in H(2)S detection.

PMID- 23012550
TI  - Dynamics of Ras complexes observed in living cells.
AB  - K-Ras works as a switch in many important intracellular signaling pathways and
      plays important roles in cell growth, proliferation, differentiation and
      carcinogenesis. For signal transduction from K-Ras to Raf1, the best
      characterized effector of K-Ras, the general view is that Ras recruits Raf1 from
      the cytoplasm to the cell membrane. To elucidate this process, we constructed a
      series of fusion proteins (including Raf1 and K-Ras fused with either fluorescent
      proteins or fluorescent protein fragments) to compare subcellular localizations
      of these proteins. Bimolecular fluorescence complementation (BiFC) and a co
      transfection system were used. In the BiFC system, the K-Ras/Raf1 complexes were
      mainly located in the cell membrane, while the Raf1 control was uniformly
      distributed in the cytoplasm. However, the complexes of Raf1 and K-RasC185S, a K
      Ras mutant which loses membrane-localization, were also able to accumulate in the
      cell membrane. In contrast, an apparent cytosolic distribution pattern was
      observed in cells co-transfected with mcerulean-Raf1 and EGFP-K-RasC185S,
      suggesting that the membrane localization of K-Ras/Raf1 complexes is not entirely
      dependent on K-Ras, and that other factors, such as the irreversible conformation
      formed between K-Ras and Raf1 may play a role. This study sheds light on the
      interaction between K-Ras and Raf1 and provides a practical method to elucidate
      the mechanism underlying K-Ras and Raf1 binding to the cell membrane.

PMID- 23012551
TI  - A fully sensorized cooperative robotic system for surgical interventions.
AB  - In this research a fully sensorized cooperative robot system for manipulation of
      needles is presented. The setup consists of a DLR/KUKA Light Weight Robot III
      especially designed for safe human/robot interaction, a FD-CT robot-driven
      angiographic C-arm system, and a navigation camera. Also, new control strategies
      for robot manipulation in the clinical environment are introduced. A method for
      fast calibration of the involved components and the preliminary accuracy tests of
      the whole possible errors chain are presented. Calibration of the robot with the
      navigation system has a residual error of 0.81 mm (rms) with a standard deviation
      of +/- 0.41 mm. The accuracy of the robotic system while targeting fixed points
      at different positions within the workspace is of 1.2 mm (rms) with a standard
      deviation of +/- 0.4 mm. After calibration, and due to close loop control, the
      absolute positioning accuracy was reduced to the navigation camera accuracy which
      is of 0.35 mm (rms). The implemented control allows the robot to compensate for
      small patient movements.

PMID- 23012552
TI  - An enhanced MEMS error modeling approach based on Nu-Support Vector Regression.
AB  - Micro Electro Mechanical System (MEMS)-based inertial sensors have made possible
      the development of a civilian land vehicle navigation system by offering a low
      cost solution. However, the accurate modeling of the MEMS sensor errors is one of
      the most challenging tasks in the design of low-cost navigation systems. These
      sensors exhibit significant errors like biases, drift, noises; which are
      negligible for higher grade units. Different conventional techniques utilizing
      the Gauss Markov model and neural network method have been previously utilized to
      model the errors. However, Gauss Markov model works unsatisfactorily in the case
      of MEMS units due to the presence of high inherent sensor errors. On the other
      hand, modeling the random drift utilizing Neural Network (NN) is time consuming,
      thereby affecting its real-time implementation. We overcome these existing
      drawbacks by developing an enhanced Support Vector Machine (SVM) based error
      model. Unlike NN, SVMs do not suffer from local minimisation or over-fitting
      problems and delivers a reliable global solution. Experimental results proved
      that the proposed SVM approach reduced the noise standard deviation by 10-35% for
      gyroscopes and 61-76% for accelerometers. Further, positional error drifts under
      static conditions improved by 41% and 80% in comparison to NN and GM approaches.

PMID- 23012553
TI  - A portable and power-free microfluidic device for rapid and sensitive lead (Pb2+)
      detection.
AB  - A portable and power-free microfluidic device was designed for rapid and
      sensitive detection of lead (Pb(2+)). 11-mercaptoundecanoic acid (MUA)
      functionalized gold nanoparticles (MUA-AuNPs) aggregated in the presence of
      Pb(2+) for the chelation mechanism. When we performed this analysis on a
      polydimethylsiloxane (PDMS) microfluidic chip, the aggregations deposited onto
      the surface of chip and formed dark lines along the laminar flows in the zigzag
      microchannels. This visual result can be observed by the naked eye through a
      microscope or just a drop of water as a magnifier. Ten MUM Pb(2+) was
      successfully detected.

PMID- 23012554
TI  - A Bayesian framework for the automated online assessment of sensor data quality.
AB  - Online automated quality assessment is critical to determine a sensor's fitness
      for purpose in real-time applications. A Dynamic Bayesian Network (DBN) framework
      is proposed to produce probabilistic quality assessments and represent the
      uncertainty of sequentially correlated sensor readings. This is a novel framework
      to represent the causes, quality state and observed effects of individual sensor
      errors without imposing any constraints upon the physical deployment or measured
      phenomenon. It represents the casual relationship between quality tests and
      combines them in a way to generate uncertainty estimates of samples. The DBN was
      implemented for a particular marine deployment of temperature and conductivity
      sensors in Hobart, Australia. The DBN was shown to offer a substantial average
      improvement (34%) in replicating the error bars that were generated by experts
      when compared to a fuzzy logic approach.

PMID- 23012555
TI  - Monitoring of temperature fatigue failure mechanism for polyvinyl alcohol fiber
      concrete using acoustic emission sensors.
AB  - The applicability of acoustic emission (AE) techniques to monitor the mechanism
      of evolution of polyvinyl alcohol (PVA) fiber concrete damage under temperature
      fatigue loading is investigated. Using the temperature fatigue test, real-time AE
      monitoring data of PVA fiber concrete is achieved. Based on the AE signal
      characteristics of the whole test process and comparison of AE signals of PVA
      fiber concretes with different fiber contents, the damage evolution process of
      PVA fiber concrete is analyzed. Finally, a qualitative evaluation of the damage
      degree is obtained using the kurtosis index and b-value of AE characteristic
      parameters. The results obtained using both methods are discussed.

PMID- 23012556
TI  - Screening of aptamers on microfluidic systems for clinical applications.
AB  - The use of microfluidic systems for screening of aptamers and their biomedical
      applications are reviewed in this paper. Aptamers with different nucleic acid
      sequences have been extensively studied and the results demonstrated a strong
      binding affinity to target molecules such that they can be used as promising
      candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer
      screening protocol has been conducted with microfluidic-based devices.
      Furthermore, aptamer affinity screening by a microfluidic-based method has
      demonstrated remarkable advantages over competing traditional methods. In this
      paper, we first reviewed microfluidic systems which demonstrated efficient and
      rapid screening of a specific aptamer. Then, the clinical applications of
      screened aptamers, also performed by microfluidic systems, are further reviewed.
      These automated microfluidic systems can provide advantages over their
      conventional counterparts including more compactness, faster analysis, less
      sample/reagent consumption and automation. An aptamer-based compact microfluidic
      system for diagnosis may even lead to a point-of-care device. The use of
      microfluidic systems for aptamer screening and diagnosis is expected to continue
      growing in the near future and may make a substantial impact on biomedical
      applications.

PMID- 23012558
TI  - Carriage error identification based on cross-correlation analysis and wavelet
      transformation.
AB  - This paper proposes a novel method for identifying carriage errors. A general
      mathematical model of a guideway system is developed, based on the multi-body
      system method. Based on the proposed model, most error sources in the guideway
      system can be measured. The flatness of a workpiece measured by the PGI1240
      profilometer is represented by a wavelet. Cross-correlation analysis performed to
      identify the error source of the carriage. The error model is developed based on
      experimental results on the low frequency components of the signals. With the use
      of wavelets, the identification precision of test signals is very high.

PMID- 23012557
TI  - Synthetic biomimetic membranes and their sensor applications.
AB  - Synthetic biomimetic membranes provide biological environments to membrane
      proteins. By exploiting the central roles of biological membranes, it is possible
      to devise biosensors, drug delivery systems, and nanocontainers using a
      biomimetic membrane system integrated with functional proteins. Biomimetic
      membranes can be created with synthetic lipids or block copolymers. These
      amphiphilic lipids and polymers self-assemble in an aqueous solution either into
      planar membranes or into vesicles. Using various techniques developed to date,
      both planar membranes and vesicles can provide versatile and robust platforms for
      a number of applications. In particular, biomimetic membranes with modified
      lipids or functional proteins are promising platforms for biosensors. We review
      recent technologies used to create synthetic biomimetic membranes and their
      engineered sensors applications.

PMID- 23012559
TI  - Adaptive UAV attitude estimation employing unscented Kalman Filter, FOAM and low
      cost MEMS sensors.
AB  - Navigation employing low cost MicroElectroMechanical Systems (MEMS) sensors in
      Unmanned Aerial Vehicles (UAVs) is an uprising challenge. One important part of
      this navigation is the right estimation of the attitude angles. Most of the
      existent algorithms handle the sensor readings in a fixed way, leading to large
      errors in different mission stages like take-off aerobatic maneuvers. This paper
      presents an adaptive method to estimate these angles using off-the-shelf
      components. This paper introduces an Attitude Heading Reference System (AHRS)
      based on the Unscented Kalman Filter (UKF) using the Fast Optimal Attitude Matrix
      (FOAM) algorithm as the observation model. The performance of the method is
      assessed through simulations. Moreover, field experiments are presented using a
      real fixed-wing UAV. The proposed low cost solution, implemented in a
      microcontroller, shows a satisfactory real time performance.

PMID- 23012560
TI  - Study on elastic helical TDR sensing cable for distributed deformation detection.
AB  - In order to detect distributed ground surface deformation, an elastic helical
      structure Time Domain Reflectometry (TDR) sensing cable is shown in this paper.
      This special sensing cable consists of three parts: a silicone rubber rope in the
      center; a couple of parallel wires coiling around the rope; a silicone rubber
      pipe covering the sensing cable. By analyzing the relationship between the
      impedance and the structure of the sensing cable, the impedance model shows that
      the sensing cable impedance will increase when the cable is stretched. This
      specific characteristic is verified in the cable stretching experiment which is
      the base of TDR sensing technology. The TDR experiment shows that a positive
      reflected signal is created at the stretching deformation point on the sensing
      cable. The results show that the deformation section length and the stretching
      elongation will both affect the amplitude of the reflected signal. Finally, the
      deformation locating experiments show that the sensing cable can accurately
      detect the deformation point position on the sensing cable.

PMID- 23012561
TI  - Screening of stepping forces in an arthritic rat model using a novel analgesic
      meter and data acquisition system.
AB  - The stepping forces of normal and Freund Complete Adjuvant (FCA)-induced
      arthritic rats were studied in vivo using a proposed novel analgesic meter. An
      infrared charge-coupled device (CCD) camera and a data acquisition system were
      incorporated into the analgesic meter to determine and measure the weight of
      loads on the right hind paw before and after induction of arthritis by FCA
      injection into the paw cavity. FCA injection resulted in a significant reduction
      in the stepping force of the affected hind paw. The stepping force decreased to
      the minimum level on day 4 after the injection and then gradually increased up to
      day 25. Oral administration of prednisolone significantly increased the stepping
      forces of FCA-induced arthritic rats on days 14 and 21. These results suggest
      that the novel device is an effective tool for measuring the arthritic pain in in
      vivo studies even though walking is a dynamic condition.

PMID- 23012562
TI  - A low-cost sensor buoy system for monitoring shallow marine environments.
AB  - Monitoring of marine ecosystems is essential to identify the parameters that
      determine their condition. The data derived from the sensors used to monitor them
      are a fundamental source for the development of mathematical models with which to
      predict the behaviour of conditions of the water, the sea bed and the living
      creatures inhabiting it. This paper is intended to explain and illustrate a
      design and implementation for a new multisensor monitoring buoy system. The
      system design is based on a number of fundamental requirements that set it apart
      from other recent proposals: low cost of implementation, the possibility of
      application in coastal shallow-water marine environments, suitable dimensions for
      deployment and stability of the sensor system in a shifting environment like the
      sea bed, and total autonomy of power supply and data recording. The buoy system
      has successfully performed remote monitoring of temperature and marine pressure
      (SBE 39 sensor), temperature (MCP9700 sensor) and atmospheric pressure (YOUNG
      61302L sensor). The above requirements have been satisfactorily validated by
      operational trials in a marine environment. The proposed buoy sensor system thus
      seems to offer a broad range of applications.

PMID- 23012563
TI  - A survey on gas sensing technology.
AB  - Sensing technology has been widely investigated and utilized for gas detection.
      Due to the different applicability and inherent limitations of different gas
      sensing technologies, researchers have been working on different scenarios with
      enhanced gas sensor calibration. This paper reviews the descriptions, evaluation,
      comparison and recent developments in existing gas sensing technologies. A
      classification of sensing technologies is given, based on the variation of
      electrical and other properties. Detailed introduction to sensing methods based
      on electrical variation is discussed through further classification according to
      sensing materials, including metal oxide semiconductors, polymers, carbon
      nanotubes, and moisture absorbing materials. Methods based on other kinds of
      variations such as optical, calorimetric, acoustic and gas-chromatographic, are
      presented in a general way. Several suggestions related to future development are
      also discussed. Furthermore, this paper focuses on sensitivity and selectivity
      for performance indicators to compare different sensing technologies, analyzes
      the factors that influence these two indicators, and lists several corresponding
      improved approaches.

PMID- 23012564
TI  - A simplified baseband prefilter model with adaptive Kalman Filter for ultra-tight
      COMPASS/INS integration.
AB  - COMPASS is an indigenously developed Chinese global navigation satellite system
      and will share many features in common with GPS (Global Positioning System).
      Since the ultra-tight GPS/INS (Inertial Navigation System) integration shows its
      advantage over independent GPS receivers in many scenarios, the federated ultra
      tight COMPASS/INS integration has been investigated in this paper, particularly,
      by proposing a simplified prefilter model. Compared with a traditional prefilter
      model, the state space of this simplified system contains only carrier phase,
      carrier frequency and carrier frequency rate tracking errors. A two-quadrant
      arctangent discriminator output is used as a measurement. Since the code tracking
      error related parameters were excluded from the state space of traditional
      prefilter models, the code/carrier divergence would destroy the carrier tracking
      process, and therefore an adaptive Kalman filter algorithm tuning process noise
      covariance matrix based on state correction sequence was incorporated to
      compensate for the divergence. The federated ultra-tight COMPASS/INS integration
      was implemented with a hardware COMPASS intermediate frequency (IF), and INS's
      accelerometers and gyroscopes signal sampling system. Field and simulation test
      results showed almost similar tracking and navigation performances for both the
      traditional prefilter model and the proposed system; however, the latter largely
      decreased the computational load.

PMID- 23012565
TI  - A novel instrumentation circuit for electrochemical measurements.
AB  - In this paper, a novel signal processing circuit which can be used for the
      measurement of H(+) ion and urea concentration is presented. A potentiometric
      method is used to detect the concentrations of H(+) ions and urea by using H(+)
      ion-selective electrodes and urea electrodes, respectively. The experimental data
      shows that this measuring structure has a linear pH response for the
      concentration range within pH 2 and 12, and the dynamic range for urea
      concentration measurement is in the range of 0.25 to 64 mg/dL. The designed
      instrumentation circuit possesses a calibration function and it can be applied to
      different sensing electrodes for electrochemical analysis. It possesses the
      advantageous properties of being multi-purpose, easy calibration and low cost.

PMID- 23012566
TI  - Design and analysis of a compact precision positioning platform integrating
      strain gauges and the piezoactuator.
AB  - Miniaturization precision positioning platforms are needed for in situ
      nanomechanical test applications. This paper proposes a compact precision
      positioning platform integrating strain gauges and the piezoactuator. Effects of
      geometric parameters of two parallel plates on Von Mises stress distribution as
      well as static and dynamic characteristics of the platform were studied by the
      finite element method. Results of the calibration experiment indicate that the
      strain gauge sensor has good linearity and its sensitivity is about 0.0468
      mV/MUm. A closed-loop control system was established to solve the problem of
      nonlinearity of the platform. Experimental results demonstrate that for the
      displacement control process, both the displacement increasing portion and the
      decreasing portion have good linearity, verifying that the control system is
      available. The developed platform has a compact structure but can realize
      displacement measurement with the embedded strain gauges, which is useful for the
      closed-loop control and structure miniaturization of piezo devices. It has
      potential applications in nanoindentation and nanoscratch tests, especially in
      the field of in situ nanomechanical testing which requires compact structures.

PMID- 23012567
TI  - SEMAT--the next generation of inexpensive marine environmental monitoring and
      measurement systems.
AB  - There is an increasing need for environmental measurement systems to further
      science and thereby lead to improved policies for sustainable management. Marine
      environments are particularly hostile and extremely difficult for deploying
      sensitive measurement systems. As a consequence the need for data is greatest in
      marine environments, particularly in the developing economies/regions. Expense is
      typically the most significant limiting factor in the number of measurement
      systems that can be deployed, although technical complexity and the consequent
      high level of technical skill required for deployment and servicing runs a close
      second. This paper describes the Smart Environmental Monitoring and Analysis
      Technologies (SEMAT) project and the present development of the SEMAT technology.
      SEMAT is a "smart" wireless sensor network that uses a commodity-based approach
      for selecting technologies most appropriate to the scientifically driven marine
      research and monitoring domain/field. This approach allows for significantly
      cheaper environmental observation systems that cover a larger geographical area
      and can therefore collect more representative data. We describe SEMAT's goals,
      which include: (1) The ability to adapt and evolve; (2) Underwater wireless
      communications; (3) Short-range wireless power transmission; (4) Plug and play
      components; (5) Minimal deployment expertise; (6) Near real-time analysis tools;
      and (7) Intelligent sensors. This paper illustrates how the capacity of the
      system has been improved over three iterations towards realising these goals. The
      result is an inexpensive and flexible system that is ideal for short-term
      deployments in shallow coastal and other aquatic environments.

PMID- 23012568
TI  - Investigation of interactive effects on water flow and solute transport in sandy
      loam soil using time domain reflectometry.
AB  - Surface-applied chemicals move through the unsaturated zone with complex flow and
      transport processes due to soil heterogeneity and reach the saturated zone,
      resulting in groundwater contamination. Such complex processes need to be studied
      by advanced measurement and modeling techniques to protect soil and water
      resources from contamination. In this study, the interactive effects of factors
      like soil structure, initial soil water content (SWC), and application rate on
      preferential flow and transport were studied in a sandy loam field soil using
      measurement (by time domain reflectometry (TDR)) and modeling (by MACRO and
      VS2DTI) techniques. In addition, statistical analyses were performed to compare
      the means of the measured and modeled SWC and EC, and solute transport parameters
      (pore water velocity and dispersion coefficient) in 12 treatments. Research
      results showed that even though the effects of soil structural conditions on
      water and solute transport were not so clear, the applied solution moved lower
      depths in the profiles of wet versus dry initial SWC and high application rate
      versus low application rates. The effects of soil structure and initial SWC on
      water and solute movement could be differentiated under the interactive
      conditions, but the effects of the application rates were difficult to
      differentiate under different soil structural and initial SWC conditions.
      Modeling results showed that MACRO had somewhat better performance than VS2DTI in
      the estimation of SWC and EC with space and time, but overall both models had
      relatively low performances. The means of SWC, EC, and solute transport
      parameters of the 12 treatments were divided into some groups based on the
      statistical analyses, indicating different flow and transport characteristics or
      a certain degree nonuniform or preferential flow and transport in the soil.
      Conducting field experiments with more interactive factors and applying the
      models with different approaches may allow better understanding of flow and
      transport processes in addition to the simulations of them in the unsaturated
      zone.

PMID- 23012569
TI  - Correcting the temperature influence on soil capacitance sensors using diurnal
      temperature and water content cycles.
AB  - The influence of temperature on the dielectric permittivity of soil is the result
      of counteracting effect that depends on the soil's composition and mineralogy. In
      this paper, laboratory experiments showed that for a given water content, the
      soil dielectric permittivity was linearly related to the temperature, with a
      slope (alpha) that varied between samples taken in the same soil. These
      variations are difficult to predict and therefore, a simple and straightforward
      algorithm was designed to estimate alpha based on the diurnal patterns of both
      the measured dielectric permittivity and the soil temperature. The underlying
      idea is to assume that soil water content variations can be known with a
      reasonable accuracy over an appropriate time window within a day. This allows
      determining the contribution of the soil water content to the dielectric
      permittivity variations and then, the difference with the observed measurements
      is attributed to the soil temperature. Implementation of the correction methods
      in a large number of experiments significantly improved the physical meaning of
      the temporal evolution of the soil water content as the daily cycles for probes
      located near the surface or the long-term variations for more deeply installed
      probes.

PMID- 23012570
TI  - Sensitivity of a label-free guided-mode resonant optical biosensor with different
      modes.
AB  - Sensitivity is a key factor in the performance of a sensor. To achieve maximum
      guided-mode resonant optical biosensor sensitivity, a comparison of biosensor
      sensitivity for Transverse Electric (TE) and Transverse Magnetic (TM) modes based
      on the distribution of electric fields is presented in this article. A label-free
      guided-mode resonant optical biosensor is designed using the quarter-wave anti
      reflection method to reflect only a narrow band of wavelengths modulated by the
      adsorption of a biochemical material on the sensor surface at the reflected
      frequency. With the distribution of electric fields simulated according to the
      Rigorous Coupled Wave Analysis (RCWA) theory, it is found that the full width at
      half maximum of the TM mode is (~ 4 nm) narrower than that of the TE mode (~ 20
      nm), and the surface sensitivity of the TE mode incident light is three times
      that of the TM mode. It is proposed in this article that the light mode plays an
      important role in the sensitivity of guided-mode resonant biosensors.

PMID- 23012571
TI  - Ubiquitous geo-sensing for context-aware analysis: exploring relationships
      between environmental and human dynamics.
AB  - Ubiquitous geo-sensing enables context-aware analyses of physical and social
      phenomena, i.e., analyzing one phenomenon in the context of another. Although
      such context-aware analysis can potentially enable a more holistic understanding
      of spatio-temporal processes, it is rarely documented in the scientific
      literature yet. In this paper we analyzed the collective human behavior in the
      context of the weather. We therefore explored the complex relationships between
      these two spatio-temporal phenomena to provide novel insights into the dynamics
      of urban systems. Aggregated mobile phone data, which served as a proxy for
      collective human behavior, was linked with the weather data from climate stations
      in the case study area, the city of Udine, Northern Italy. To identify and
      characterize potential patterns within the weather-human relationships, we
      developed a hybrid approach which integrates several spatio-temporal statistical
      analysis methods. Thereby we show that explanatory factor analysis, when applied
      to a number of meteorological variables, can be used to differentiate between
      normal and adverse weather conditions. Further, we measured the strength of the
      relationship between the 'global' adverse weather conditions and the spatially
      explicit effective variations in user-generated mobile network traffic for three
      distinct periods using the Maximal Information Coefficient (MIC). The analyses
      result in three spatially referenced maps of MICs which reveal interesting
      insights into collective human dynamics in the context of weather, but also
      initiate several new scientific challenges.

PMID- 23012572
TI  - A micro-machined gyroscope for rotating aircraft.
AB  - In this paper we present recent work on the design, fabrication by silicon
      micromachining, and packaging of a new gyroscope for stabilizing the autopilot of
      rotating aircraft. It operates based on oscillation of the silicon pendulum
      between two torsion girders for detecting the Coriolis force. The oscillation of
      the pendulum is initiated by the rolling and deflecting motion of the rotating
      carrier. Therefore, the frequency and amplitude of the oscillation are
      proportional to the rolling frequency and deflecting angular rate of the rotating
      carrier, and are measured by the sensing electrodes. A modulated pulse with
      constant amplitude and unequal width is obtained by a linearizing process of the
      gyroscope output signal and used to control the deflection of the rotating
      aircraft. Experimental results show that the gyroscope has a resolution of 0.008 
      degrees /s and a bias of 56.18  degrees /h.

PMID- 23012573
TI  - Harnessing the interaction continuum for subtle assisted living.
AB  - People interact with each other in many levels of attention, intention and
      meaning. This Interaction Continuum is used daily to deal with different
      contexts, adapting the interaction to communication needs and available
      resources. Nevertheless, computer-supported interaction has mainly focused on the
      most direct, explicit and intrusive types of human to human Interaction such as
      phone calls, emails, or video conferences. This paper presents the results of
      exploring and exploiting the potentials of undemanding interaction mechanisms,
      paying special attention to subtle communication and background interaction. As
      we argue the benefits of this type of interaction for people with special needs,
      we present a theoretical framework to define it and propose a proof of concept
      based on Augmented Objects and a color codification mechanism. Finally, we
      evaluate and analyze the strengths and limitations of such approach with people
      with cognitive disabilities.

PMID- 23012574
TI  - Characterizing the moisture content of tea with diffuse reflectance spectroscopy
      using wavelet transform and multivariate analysis.
AB  - Effects of the moisture content (MC) of tea on diffuse reflectance spectroscopy
      were investigated by integrated wavelet transform and multivariate analysis. A
      total of 738 representative samples, including fresh tea leaves, manufactured tea
      and partially processed tea were collected for spectral measurement in the 325
      1,075 nm range with a field portable spectroradiometer. Then wavelet transform
      (WT) and multivariate analysis were adopted for quantitative determination of the
      relationship between MC and spectral data. Three feature extraction methods
      including WT, principal component analysis (PCA) and kernel principal component
      analysis (KPCA) were used to explore the internal structure of spectral data.
      Comparison of those three methods indicated that the variables generated by WT
      could efficiently discover structural information of spectral data. Calibration
      involving seeking the relationship between MC and spectral data was executed by
      using regression analysis, including partial least squares regression, multiple
      linear regression and least square support vector machine. Results showed that
      there was a significant correlation between MC and spectral data (r = 0.991,
      RMSEP = 0.034). Moreover, the effective wavelengths for MC measurement were
      detected at range of 888-1,007 nm by wavelet transform. The results indicated
      that the diffuse reflectance spectroscopy of tea is highly correlated with MC.

PMID- 23012575
TI  - Electromagnetic wave propagation in Body Area Networks using the Finite
      Difference-Time-Domain method.
AB  - A rigorous full-wave solution, via the Finite-Difference-Time-Domain (FDTD)
      method, is performed in an attempt to obtain realistic communication channel
      models for on-body wireless transmission in Body-Area-Networks (BANs), which are
      local data networks using the human body as a propagation medium. The problem of
      modeling the coupling between body mounted antennas is often not amenable to
      attack by hybrid techniques owing to the complex nature of the human body. For
      instance, the time-domain Green's function approach becomes more involved when
      the antennas are not conformal. Furthermore, the human body is irregular in shape
      and has dispersion properties that are unique. One consequence of this is that we
      must resort to modeling the antenna network mounted on the body in its entirety,
      and the number of degrees of freedom (DoFs) can be on the order of billions. Even
      so, this type of problem can still be modeled by employing a parallel version of
      the FDTD algorithm running on a cluster. Lastly, we note that the results of
      rigorous simulation of BANs can serve as benchmarks for comparison with the
      abundance of measurement data.

PMID- 23012576
TI  - Foot plantar pressure measurement system: a review.
AB  - Foot plantar pressure is the pressure field that acts between the foot and the
      support surface during everyday locomotor activities. Information derived from
      such pressure measures is important in gait and posture research for diagnosing
      lower limb problems, footwear design, sport biomechanics, injury prevention and
      other applications. This paper reviews foot plantar sensors characteristics as
      reported in the literature in addition to foot plantar pressure measurement
      systems applied to a variety of research problems. Strengths and limitations of
      current systems are discussed and a wireless foot plantar pressure system is
      proposed suitable for measuring high pressure distributions under the foot with
      high accuracy and reliability. The novel system is based on highly linear
      pressure sensors with no hysteresis.

PMID- 23012577
TI  - User localization during human-robot interaction.
AB  - This paper presents a user localization system based on the fusion of visual
      information and sound source localization, implemented on a social robot called
      Maggie. One of the main requisites to obtain a natural interaction between human
      human and human-robot is an adequate spatial situation between the interlocutors,
      that is, to be orientated and situated at the right distance during the
      conversation in order to have a satisfactory communicative process. Our social
      robot uses a complete multimodal dialog system which manages the user-robot
      interaction during the communicative process. One of its main components is the
      presented user localization system. To determine the most suitable allocation of
      the robot in relation to the user, a proxemic study of the human-robot
      interaction is required, which is described in this paper. The study has been
      made with two groups of users: children, aged between 8 and 17, and adults.
      Finally, at the end of the paper, experimental results with the proposed
      multimodal dialog system are presented.

PMID- 23012578
TI  - A logistic regression model for predicting axillary lymph node metastases in
      early breast carcinoma patients.
AB  - Nodal staging in breast cancer is a key predictor of prognosis. This paper
      presents the results of potential clinicopathological predictors of axillary
      lymph node involvement and develops an efficient prediction model to assist in
      predicting axillary lymph node metastases. Seventy patients with primary early
      breast cancer who underwent axillary dissection were evaluated. Univariate and
      multivariate logistic regression were performed to evaluate the association
      between clinicopathological factors and lymph node metastatic status. A logistic
      regression predictive model was built from 50 randomly selected patients; the
      model was also applied to the remaining 20 patients to assess its validity.
      Univariate analysis showed a significant relationship between lymph node
      involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression.
      Absence of Kiss-1 remained significantly associated with positive axillary node
      status in the multivariate analysis (p = 0.018). Seven clinicopathological
      factors were involved in the multivariate logistic regression model: menopausal
      status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and
      discriminating, with an area under the receiver operating characteristic curve of
      0.702 when applied to the validation group. Moreover, there is a need discover
      more specific candidate proteins and molecular biology tools to select more
      variables which should improve predictive accuracy.

PMID- 23012579
TI  - Development of an undergraduate bioinformatics degree program at a liberal arts
      college.
AB  - The highly interdisciplinary field of bioinformatics has emerged as a powerful
      modern science. There has been a great demand for undergraduate- and graduate
      level trained bioinformaticists in the industry as well in the academia. In order
      to address the needs for trained bioinformaticists, its curriculum must be
      offered at the undergraduate level, especially at four-year colleges, where a
      majority of the United States gets its education. There are many challenges in
      developing an undergraduate-level bioinformatics program that needs to be
      carefully designed as a well-integrated and cohesive interdisciplinary curriculum
      that prepares the students for a wide variety of career options. This article
      describes the challenges of establishing a highly interdisciplinary undergraduate
      major, the development of an undergraduate bioinformatics degree program at
      Ramapo College of New Jersey, and lessons learned in the last 10 years during its
      management.

PMID- 23012580
TI  - Thriving in multidisciplinary research: advice for new bioinformatics students.
AB  - The sciences have seen a large increase in demand for students in bioinformatics
      and multidisciplinary fields in general. Many new educational programs have been
      created to satisfy this demand, but navigating these programs requires a non
      traditional outlook and emphasizes working in teams of individuals with distinct
      yet complementary skill sets. Written from the perspective of a current
      bioinformatics student, this article seeks to offer advice to prospective and
      current students in bioinformatics regarding what to expect in their educational
      program, how multidisciplinary fields differ from more traditional paths, and
      decisions that they will face on the road to becoming successful, productive
      bioinformaticists.

PMID- 23012581
TI  - Perspectives on an education in computational biology and medicine.
AB  - The mainstream application of massively parallel, high-throughput assays in
      biomedical research has created a demand for scientists educated in Computational
      Biology and Bioinformatics (CBB). In response, formalized graduate programs have
      rapidly evolved over the past decade. Concurrently, there is increasing need for
      clinicians trained to oversee the responsible translation of CBB research into
      clinical tools. Physician-scientists with dedicated CBB training can facilitate
      such translation, positioning themselves at the intersection between
      computational biomedical research and medicine. This perspective explores key
      elements of the educational path to such a position, specifically addressing: 1)
      evolving perceptions of the role of the computational biologist and the impact on
      training and career opportunities; 2) challenges in and strategies for obtaining
      the core skill set required of a biomedical researcher in a computational world;
      and 3) how the combination of CBB with medical training provides a logical
      foundation for a career in academic medicine and/or biomedical research.

PMID- 23012582
TI  - Systematic deciphering of cancer genome networks.
AB  - When growth regulatory genes are damaged in a cell, it may become cancerous.
      Current technological advances in the last decade have allowed the
      characterization of the whole genome of these cells by directly or indirectly
      measuring DNA changes. Complementary analyses were developed to make sense of the
      massive amounts of data generated. A large majority of these analyses were
      developed to construct interaction networks between genes from, primarily,
      expression array data. We review the current technologies and analyses that have
      developed in the last decade. We further argue that as cancer genomics evolves
      from single gene validations to gene network inferences, new analyses must be
      developed for the different technological platforms.

PMID- 23012583
TI  - Integrated analysis of tumor samples sheds light on tumor heterogeneity.
AB  - The heterogeneity of tumor samples is a major challenge in the analysis of high
      throughput profiling of tumor biopsies and cell lines. The measured aggregate
      signals of multigenerational progenies often represent an average of several
      tumor subclones with varying genomic aberrations and different gene expression
      levels. The goal of the present study was to integrate copy number analyses from
      SNP-arrays and karyotyping, gene expression profiling, and pathway analyses to
      detect heterogeneity, identify driver mutations, and explore possible mechanisms
      of tumor evolution. We showed the heterogeneity of the studied samples,
      characterized the global copy number alteration profiles, and identified genes
      whose copy number status and expression levels were aberrant. In particular, we
      identified a recurrent association between two BRAF(V600E) and BRAF(V600K)
      mutations and changes in DKK1 gene expression levels, which might indicate an
      association between the BRAF and WNT pathways. These findings show that the
      integrated approaches used in the present study can robustly address the
      challenging issue of tumor heterogeneity in high-throughput profiling.

PMID- 23012584
TI  - The future of medical diagnostics: large digitized databases.
AB  - The electronic health record mandate within the American Recovery and
      Reinvestment Act of 2009 will have a far-reaching affect on medicine. In this
      article, we provide an in-depth analysis of how this mandate is expected to
      stimulate the production of large-scale, digitized databases of patient
      information. There is evidence to suggest that millions of patients and the
      National Institutes of Health will fully support the mining of such databases to
      better understand the process of diagnosing patients. This data mining likely
      will reaffirm and quantify known risk factors for many diagnoses. This
      quantification may be leveraged to further develop computer-aided diagnostic
      tools that weigh risk factors and provide decision support for health care
      providers. We expect that creation of these databases will stimulate the
      development of computer-aided diagnostic support tools that will become an
      integral part of modern medicine.

PMID- 23012585
TI  - How the electronic health record will change the future of health care.
AB  - Genetic testing is expected to play a critical role in patient care in the near
      future. Advances in genomic research have the potential to impact medicine in
      very tangible and direct ways, from carrier screening to disease diagnosis and
      prognosis to targeted treatments and personalized medicine. However, numerous
      barriers to widespread adoption of genetic testing continue to exist, and health
      information technology will be a critical means of addressing these challenges.
      Electronic health records (EHRs) are a digital replacement for the traditional
      paper-based patient chart designed to improve the quality of patient care. EHRs
      have become increasingly essential to managing the wealth of existing clinical
      information that now includes genetic information extracted from the patient
      genome. The EHR is capable of changing health care in the future by transforming
      the way physicians use genomic information in the practice of medicine.

PMID- 23012587
TI  - On the 25th Lee E. Farr lecture at the Yale School of Medicine.

PMID- 23012588
TI  - Hormone resistance in diabetes and obesity: insulin, leptin, and FGF21.
AB  - This an edited transcript of the Lee E. Farr Lecture given by Dr. Jeffrey Flier
      on May 8, 2012, at the culmination of the annual Student Research Day at the Yale
      School of Medicine. In this presentation, Dr. Flier discusses his and his wife's
      research on insulin, leptin, and FGF21 in the context of his reflections upon his
      life's work and his advice for young investigators.

PMID- 23012589
TI  - A report of the James Watson lecture at Yale University.
AB  - In March 2012, Nobel Prize winner James Watson gave a seminar at Yale University
      entitled "Driven by Ideas." In his lecture, Watson discussed his personal vision
      for the future of science, specifically addressing how the scientific community
      should approach developing anticancer agents. He discussed the use of glycolytic
      inhibitors as anticancer agents due to the Warburg effect, as well as the
      benefits of metformin and anti-inflammatory drugs to help prevent cancer. He also
      compared drugs that target cell proliferation instead of targeting cell growth.
      Additionally, Watson commented on the mechanisms for how research should be
      conducted in the laboratory.

PMID- 23012586
TI  - The role of circadian clocks in metabolic disease.
AB  - The circadian clock is a highly conserved timing system, resonating physiological
      processes to 24-hour environmental cycles. Circadian misalignment is emerging as
      a risk factor of metabolic disease. The molecular clock resides in all metabolic
      tissues, the dysfunction of which is associated with perturbed energy metabolism.
      In this article, we will review current knowledge about molecular mechanisms of
      the circadian clock and the role of clocks in the physiology and pathophysiology
      of metabolic tissues.

PMID- 23012590
TI  - Sequence thyself: personalized medicine and therapies for the future: 2012 Yale
      Healthcare Conference.
AB  - Now in its 8th year, the Yale Healthcare Conference has arguably come upon its
      most exciting and dramatic time within the U.S. health care system. Dynamic
      speakers from all over the country came together in April 2012 at Yale University
      to question, debate, creatively think, and examine challenges within health care
      organizations and institutions. One of the most prominent issues concerned the
      aftermath of sequencing the human genome and the explosion of information
      concerning gene polymorphisms and biomarkers in health and disease. Clinicians,
      scientists, and pharmaceuticals are looking to innovative individually tailored
      treatments for patients. During the conference breakout session, speakers Thomas
      Lynch, MD, director of the Yale Cancer Center and physician-in-chief of the
      Smilow Cancer Hospital, and Zen Chu, MBA, co-founder of Accelerated Medical
      Ventures and entrepreneur-in-residence at Massachusetts Institute of Technology,
      provided enriching discussion on the delivery of science and genetic care of the
      individual.

PMID- 23012591
TI  - Transforming global health with mobile technologies and social enterprises:
      global health and innovation conference.
AB  - More than 2,000 people convened for the ninth annual Global Health and Innovation
      Conference at Yale University on April 21-22, 2012. Participants discussed the
      latest innovations, ideas in development, lessons learned, opportunities and
      challenges in global health activities. Several themes emerged, including the
      important role of frontline workers, strengthening health systems, leveraging
      social media, and sustainable and impact-driven philanthropy. Overall, the major
      outcome of the conference was the increased awareness of the potential of mobile
      technologies and social enterprises in transforming global health. Experts warned
      that donations and technological advances alone will not transform global health
      unless there are strong functioning health infrastructures and improved
      workforce. It was noted that there is a critical need for an integrated systems
      approach to global health problems and a need for scaling up promising pilot
      projects. Lack of funding, accountability, and sustainability were identified as
      major challenges in global health.

PMID- 23012592
TI  - Prostate cancer screening trends in a large, integrated health care system.
AB  - BACKGROUND: As the debate over the effectiveness of prostate-specific antigen
      (PSA) screening for prostate cancer continues, it is increasingly important to
      understand how PSA screening occurs in general-practice settings. METHODS: We
      conducted a retrospective cohort study within Kaiser Permanente Southern
      California, a large integrated health care system. Men aged 35 years and older at
      baseline, in 1998, were eligible. The proportion of men who underwent PSA
      screening was estimated and compared across groups defined by patient and
      physician characteristics. We also evaluated trends in screening across time and
      serum PSA levels for all subgroups. RESULTS: Of 2,061,047 men, 572,306 (28%)
      underwent PSA screening from 1998 through 2007. Patterns of PSA screening varied
      modestly by age, race, and physician. The lowest frequencies of screening
      occurred among men younger than age 45 years (19%) and men ages 85 years and
      older (13%). PSA screening was most common among white men (33.5%) and in men
      seen by physicians of the same race/ethnicity (32%), compared with men with
      physicians of disparate race/ethnicity (26%, p < 0.001). PSA screening increased
      over time for all racial/ethnic groups and among men age 75 years and older but
      decreased over time for men younger than age 75 years old. CONCLUSIONS: Nearly 1
      in 4 eligible men underwent PSA screening from 1998 through 2007, and screening
      varied only modestly by patient and physician characteristics. Estimates of the
      frequency of PSA screening in general-practice settings can inform the debate and
      provide useful insight as to how changes in cancer screening guidelines would
      alter practice patterns in an increasingly integrated health care environment.

PMID- 23012593
TI  - A colorectal "care bundle" to reduce surgical site infections in colorectal
      surgeries: a single-center experience.
AB  - BACKGROUND: Kaiser Sunnyside Medical Center has participated in the American
      College of Surgeons National Surgical Quality Improvement Program (NSQIP) since
      January 2006. Data on general and colorectal surgical site infections (SSIs)
      demonstrated a need for improvement in SSI rates. OBJECTIVE: To evaluate
      application of a "care bundle" for patients undergoing colorectal operations,
      with the goal of reducing overall SSI rates. METHODS: We prospectively
      implemented multiple interventions, with retrospective analysis of data using the
      NSQIP database. The overall, superficial, deep, and organ/space SSI rates were
      compared before and after implementation of this colorectal care bundle. RESULTS:
      Between January 2006 and December 2009, there were 430 colorectal cases in our
      NSQIP report with 91 infections, an overall rate of 21.16%. Between January 2010,
      when the colorectal care bundle was implemented, and June 2011, there were 195
      cases and 13 infections, a 6.67% overall rate. The absolute decrease of 14.49% is
      significant (p < 0.0001). The rate of superficial SSI decreased from 15.12% to
      3.59% (p < 0.0001). The rates for deep and organ/space SSI also showed a
      decrease; however, this was not statistically significant. The NSQIP observed-to
      expected ratio for colorectal SSI decreased from a range of 1.27 to 1.83 before
      implementation to 0.54 after implementation (fiscal year 2010). CONCLUSIONS: Our
      institution was a NSQIP high outlier in general surgery SSIs and had a high
      proportion of these cases represented in colorectal cases. By instituting a care
      bundle composed of core and adjunct strategies, we significantly decreased our
      rate of colorectal SSIs.

PMID- 23012594
TI  - Reductions in pain medication use associated with traditional Chinese medicine
      for chronic pain.
AB  - CONTEXT: Participants in a randomized trial of traditional Chinese medicine (TCM)
      for temporomandibular joint dysfunction (TMD) had a linear decline in pain over
      16 TCM visits. OBJECTIVE: To investigate whether reductions in pain among
      participants receiving TCM can be explained by increased use of pain medications,
      or whether use of pain medications also declined in this group. DESIGN: One
      hundred sixty-eight participants with TMD were treated with TCM or enhanced self
      care according to a stepped-care design. Those for whom self-care failed were
      sequentially randomized to further self-care or TCM. This report includes 111
      participants during their first 16 TCM visits. The initial 8 visits occurred more
      than once a week; participants and practitioners determined the frequency of
      subsequent visits. OUTCOME MEASURES: Average pain (visual analog scale, range 0
      10) and morphine and aspirin dose equivalents. RESULTS: The sample was 87% women
      and the average age was 44 +/- 13 years. Average pain of narcotics users (n = 21)
      improved by 2.73 units over 16 visits (p < 0.001). Overall narcotics use trended
      downward until visit 11 (-3.27 doses/week, p = 0.156), and then trended upward
      until week 16 (+4.29 doses/week, p = 0.264). Among those using narcotics, use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) declined linearly over visits 1-16
      (-1.94 doses/week, p = 0.002).Among the top quartile of NSAID-only users (n =
      22), average pain decreased linearly over 16 visits (-1.52 units, p = 0.036).
      Overall NSAID doses/week declined between visits 1 and 7 (-9.95 doses/week, p <
      0.001) and then remained stable through 16 visits. NSAID use also declined among
      the third quartile (n = 23) and remained low and stable among the lower half
      (sorted by total intake) of NSAID users. CONCLUSIONS: Among the heaviest NSAID
      users, we observed a short-term reduction in NSAID use that was sustained as TCM
      visits became less frequent. There was no indication that pain reduction during
      TCM treatment was influenced by drug use.

PMID- 23012595
TI  - Ultrasound measurements in hypertrophic pyloric stenosis: don't let the numbers
      fool you.
AB  - BACKGROUND: Ultrasound guidelines for hypertrophic pyloric stenosis (HPS) have
      fixed minimum measurements and do not account for variation in patient weight or
      age. We sought to determine if preoperative pyloric measurements correlated with
      weight and age in patients with surgically proven HPS. METHODS: A retrospective
      analysis was conducted of 189 patients with HPS treated at a single institution
      over a 5-year period (2005 to 2010). Pearson correlation and linear regression
      analyses were used to determine if there were statistically significant
      associations between these combinations of factors: age and pyloric muscle
      thickness, weight and pyloric muscle thickness, age and pyloric length, and
      weight and pyloric length. RESULTS: Patients' mean age was 4.6 weeks (range, 1 to
      17 weeks). Their mean weight was 3.9 kg (range, 2.5 to 8.0 kg). Mean pyloric
      muscle thickness was 0.42 cm (range, 0.18 to 0.86 cm), and mean pyloric length
      was 1.89 cm (range, 0.8 to 2.8 cm). Pearson correlation coefficient analysis
      showed a significant relationship between age and muscle thickness (r = 0.35, p <
      0.001) as well as weight and muscle thickness (r = 0.24, p = 0.001). No
      significant relationship existed between pyloric length and age or weight. Linear
      regression analysis demonstrated similar results. CONCLUSION: In patients with
      HPS, pyloric muscle thickness was directly related to age and weight.
      Practitioners should be aware that smaller and younger infants with a clinical
      diagnosis of HPS may still truly have HPS even though the minimum diagnostic
      criterion for muscle thickness or length is not found on ultrasound.

PMID- 23012596
TI  - Living with advanced illness: longitudinal study of patient, family, and
      caregiver needs.
AB  - BACKGROUND AND OBJECTIVES: Inpatient palliative care (IPC) consults are
      associated with improved quality of care and less intensive utilization. However,
      little is known about how the needs of patients with advanced illness and the
      needs of their families and caregivers evolve or how effectively those needs are
      addressed. The objectives of this study were 1) to summarize findings in the
      literature about the needs of patients with advanced illness and the needs of
      their families and caregivers; 2) to identify the primary needs of patients,
      families, and caregivers across the continuum of care from their vantage point;
      and 3) to learn how IPC teams affect the care experience. METHODS: We used a
      longitudinal, video-ethnographic approach to observe and to interview 12 patients
      and their families before, during, and after an IPC consult at 3 urban medical
      centers. Additional interviews took place up to 12 months after discharge.
      RESULTS: Five patient/family/caregiver needs were important to all family units.
      IPC teams responded effectively to a variety of needs that were not met in the
      hospital, but some postdischarge needs, beyond the scope of IPC or health care
      coverage, were not completely met. CONCLUSION: Findings built upon the needs
      identified in the literature. The longitudinal approach highlighted changes in
      needs of patients, families, and caregivers in response to emerging medical and
      nonmedical developments, from their perspective. Areas for improvement include
      clear, integrated communications in the hospital and coordinated, comprehensive
      postdischarge support for patients not under hospice care and for their
      caregivers.

PMID- 23012598
TI  - Engaging patients in managing their health care: patient perceptions of the
      effect of a total joint replacement presurgical class.
AB  - OBJECTIVE: To engage patients in managing their health care especially in
      relation to a total joint replacement (TJR). With the aging of the American
      population and the advent of new technology, there is an increase in TJRs. As the
      pendulum swings from evidence-based medicine to patient-centered medicine,
      presurgical education is preparing patients for their surgical experience. Most
      research studies on such education are quantitative in nature, preventing
      patients' voices from being heard. METHODS: Using a success case narrative
      design, 24 patients mainly from the Kaiser Permanente Downey Medical Center were
      interviewed regarding their pre- and postsurgical experiences. RESULTS: The study
      findings demonstrate that patient education, in the form of classes, with
      recognition of the participants' physical needs, social needs, concrete supports,
      and psychological needs as well as the willingness of the participants to work
      with their health care team can promote patient engagement and improved quality
      of life. CONCLUSION: The TJR class was found to promote a sense of social
      connectedness and fostered participants' independence. The results of this study
      can assist health care professionals to improve their practice by designing
      presurgical programs to meet the needs of their patients.

PMID- 23012597
TI  - Sociodemographic characteristics of members of a large, integrated health care
      system: comparison with US Census Bureau data.
AB  - BACKGROUND: Data from the memberships of large, integrated health care systems
      can be valuable for clinical, epidemiologic, and health services research, but a
      potential selection bias may threaten the inference to the population of
      interest. METHODS: We reviewed administrative records of members of Kaiser
      Permanente Southern California (KPSC) in 2000 and 2010, and we compared their
      sociodemographic characteristics with those of the underlying population in the
      coverage area on the basis of US Census Bureau data. RESULTS: We identified
      3,328,579 KPSC members in 2000 and 3,357,959 KPSC members in 2010, representing
      approximately 16% of the population in the coverage area. The distribution of sex
      and age of KPSC members appeared to be similar to the census reference population
      in 2000 and 2010 except with a slightly higher proportion of 40 to 64 year olds.
      The proportion of Hispanics/Latinos was comparable between KPSC and the census
      reference population (37.5% vs 38.2%, respectively, in 2000 and 45.2% vs 43.3% in
      2010). However, KPSC members included more blacks (14.9% vs 7.0% in 2000 and
      10.8% vs 6.5% in 2010). Neighborhood educational levels and neighborhood
      household incomes were generally similar between KPSC members and the census
      reference population, but with a marginal underrepresentation of individuals with
      extremely low income and high education. CONCLUSIONS: The membership of KPSC
      reflects the socioeconomic diversity of the Southern California census
      population, suggesting that findings from this setting may provide valid
      inference for clinical, epidemiologic, and health services research.

PMID- 23012599
TI  - A framework for making patient-centered care front and center.
AB  - The concept of patient-centered care has received increased attention in recent
      years and is now considered an essential aspiration of high-quality health care
      systems. Because of technologic advances as well as changes in the organization
      and financing of care delivery, contemporary health care has evolved tremendously
      since the concept of patient-centeredness was introduced in the late 1980s.
      Historically, those advocating patient-centered care have focused on the
      relationship between the patient and the physician or care team. Although that
      relationship is still integral, changes to the health care system suggest that a
      broader range of factors may affect the patient-centeredness of health care
      experiences. A multidimensional conceptualization of patient-centered care and
      examples from our health care system illustrate how clinical, structural, and
      interpersonal attributes can collectively influence the patient's experience. The
      proposed framework is designed to enable any health system to identify ways in
      which care could be more patient-centered and move toward a goal of making it a
      "systems property."

PMID- 23012600
TI  - Women in surgery: bright, sharp, brave, and temperate.
AB  - Women make up an increasing proportion of students entering the medical
      profession. Before 1970, women represented 6% or less of the medical student
      population. In drastic contrast, nearly half of first-time applicants to medical
      schools in 2011 were women. However, the ratio of women to men is less balanced
      among graduates from surgical residencies and among leadership positions in
      surgery. Less than 20% of full professor, tenured faculty, and departmental head
      positions are currently held by women. However, this disparity may resolve with
      time as more women who entered the field in the 1980s emerge as mature surgeons
      and leaders. The aim of this article is to review the history of women in surgery
      and to highlight individual and institutional creative modifications that can
      promote the advancement of women in surgery. A secondary aim of the article is to
      add some levity to the discussion with personal anecdotes representing the
      primary author's (ECM) personal opinions, biases, and reflections.

PMID- 23012601
TI  - Lymphoepithelial carcinoma: a case of a rare parotid gland tumor.
AB  - A 29-year-old woman presented from another hospital with a 10-month history of an
      enlarging left-sided facial mass. Computed tomographic scan revealed a mass in
      the superficial lobe of the left parotid gland with left-sided cervical
      lymphadenopathy. The patient received a total left parotidectomy and a selective
      neck dissection. Histopathologic slides revealed lymphoepithelial carcinoma (LEC)
      that stained positive for cytokeratin, as well as Epstein-Barr virus (EBV). An
      LEC of the parotid is a rare salivary gland tumor accounting for less than 1% of
      all salivary gland tumors. As reaffirmed in our case, LEC is more common in
      women, occurs primarily in the parotid gland, and has an ethnic predilection.
      Histologic analysis reveals an infiltrative, poorly differentiated tumor nestled
      in a lymphoid stroma, with near 100% positivity for EBV in endemic areas.
      Complete resection of this poorly differentiated carcinoma followed by
      postoperative radiation is essential for local control.

PMID- 23012602
TI  - Neurothekeoma in the posterior fossa: case report and literature review.
AB  - Neurothekeoma is a benign nerve sheath tumor, also known as nerve sheath myxoma.
      It arises from the cutaneous nerves of the head and neck region. In certain
      cases, neurothekeoma has been reported in the breast, oral cavity, tongue,
      maxilla, and spinal intradural space. Intracranial neurothekeoma, however, is an
      extremely rare entity, with only three cases reported in the literature: one in
      the parasellar region, one in the deep white matter, and another one in the
      cerebellopontine angle. We present the case of a 40-year-old man with a very
      large neurothekeoma present in the posterior fossa who had no neurologic deficit
      on presentation.

PMID- 23012603
TI  - Nailing the diagnosis: koilonychia.

PMID- 23012604
TI  - Image diagnosis: foot pain and fever.

PMID- 23012605
TI  - Development of a computerized intravenous insulin application (AutoCal) at Kaiser
      Permanente Northwest, integrated into Kaiser Permanente HealthConnect: impact on
      safety and nursing workload.
AB  - CONTEXT: The electronic medical record, HealthConnect, at the Kaiser Sunnyside
      Medical Center in the Northwest used scanned paper protocols for intravenous
      insulin administration. A chart review of 15 patients on intravenous insulin
      therapy using state-of-the-art paper-based column protocols revealed 40%
      deviation from the protocol. A time study of experienced nurses computing the
      insulin dose revealed an average of 2 minutes per calculation per hour to
      complete. OBJECTIVE: To improve patient safety and to reduce nursing workload
      burden with a computerized intravenous insulin calculator application connected
      to HealthConnect. SOLUTION: Using Kaiser iLab developers through innovation
      funding, a computerized protocol was developed and integrated into HealthConnect,
      with a computerized tracking system used to store and to analyze intravenous
      insulin data. OUTCOME: A review of 35 patient charts using computerized insulin
      infusion tool indicated 100% accuracy in computations with a reduction of nursing
      workload from 2 minutes to 30 seconds per calculation. CONCLUSION: Development
      and operationalizing an integrated intravenous insulin calculator into
      HealthConnect was successfully completed at the Kaiser Sunnyside Medical Center,
      with 97% nursing satisfaction scores and a promise to generate data on
      intravenous insulin therapy to refine the protocol.

PMID- 23012606
TI  - Solving the emergency care crisis in America: the power of the law and
      storytelling.
AB  - An Emergency Department visit that ended tragically prompted my yearlong journey
      to Washington, DC, and emergency rooms across the country to search for solutions
      to the national crisis in emergency care. I reached the conclusion that the
      crisis is entirely solvable, and I developed a three-part solution that includes
      1) nationally standardizing and coordinating care, 2) prioritizing resources and
      incentives in the delivery of emergency care, and 3) inspiring young clinicians
      to careers in emergency care. Physicians across America should now harness the
      power of storytelling to strengthen both the delivery of patient care and health
      care reform efforts on Capitol Hill.

PMID- 23012607
TI  - Trifecta: running on hope.

PMID- 23012608
TI  - Nosocomial infections among burn patients in Teheran, Iran: a decade later.
AB  - The aim of this study was to determine the epidemiology of nosocomial infections
      among burn patients in a tertiary burn care centre in Tehran, Iran. A cross
      sectional study was carried out during a 6-month period from August 2010 to
      January 2011 at Motahari Burn and Reconstruction Center in Tehran. Of 155
      patients, 677 samples of wound and blood were taken for culture during the course
      of hospitalization. The rate of positive culture during the 1(st), 2(nd), 3(rd),
      and 4(th) week of hospitalization were 76.3%, 99.3%, 100%, and 100%,
      respectively. On the 2(nd), 3(rd), and 4(th) week of hospitalization, Pseudomonas
      aeruginosa was the most common pathogen followed by Acinetobacter, while the
      culture positive rate for Staphylococcus spp., Enterobacteriaceae, and
      Enterococcus spp. significantly decreased (P < 0.001). In this study, 70 patients
      out of 155 (45.2%) had at least one Acinetobacter positive culture. Our results
      showed that P. aeruginosa is still the leading cause of nosocomial infections.
      Additionally, Acinetobacter has appeared as an emerging nosocomial pathogen, and
      should be considered as a serious risk. We believe that changes in burn wounds'
      bacterial colonization over time require consistent assessment and monitoring of
      these changes in any burn center.

PMID- 23012609
TI  - Current scenario in chemical burns in a developing country: Chennai, India.
AB  - Chemical burns are not uncommon in India. Both accidental and non-accidental
      chemical burns are encountered in our setting. In the paediatric age group,
      chemical burns are mainly accidental. Analysis of chemical burn admissions to the
      Burn Units of a medical college hospital, and to an exclusively tertiary care
      children's hospital in Chennai, India, from 2001 to 2010 is described. A total
      number of 75 adults and 38 children are included in the study. Detailed analysis
      of age, sex, percentage of burn total body surface area (TBSA %), causative
      agents, aetiology (accidental or non-accidental), treatment instituted,
      mortality, and outcome are reported.

PMID- 23012610
TI  - Profile of burn sepsis challenges and outcome in an exclusive children's hospital
      in Chennai, India.
AB  - A group of 273 paediatric patients admitted to Kanchi Kamakoti Childs Trust
      Hospital Burn Unit, Chennai, India between the years 2004 to 2010 were analysed
      retrospectively. Of these, 89 were suffering from sepsis and septic shock and 15
      died. Strict adherence to antibiotic administration and to the Paediatric
      Intensive Care Unit (PICU) and management protocol improved the outcome,
      especially in 2009 and 2010.

PMID- 23012611
TI  - Effect of major burns on early and late activating markers of peripheral blood T
      lymphocytes.
AB  - It is known that lymphocytes immunophenotype is a reflection of the functional
      level of the immune system. The immunosuppressive effect of major burns is also
      known for many years. T lymphocytes of 50 major burn patients were analyzed in
      base line (BL) samples at 24 hours and at 1 week and 2 weeks after burn, using
      monoclonal antibodies of CD3, CD4, CD8, CD25 (IL2R) and HLA-DR by flow cytometry
      and beta2-microglobulin (beta2-m) by ELISA. Recorded values were compared with
      those of 50 healthy donors. There was statistically significant reduction in
      absolute number of CD3 positive cells (CD3+) (p<0.000) and CD4/CD8 ratio (p=0.01)
      in the first 24 hours in comparison with controls. CD25 (IL-2R) shows
      insignificant upregulation on T lymphocytes after burn with significant
      upregulation of HLA-DR. The absolute number of CD3+ cells began to increase after
      2 weeks (p=0.03) but remained less than controls (p=0.08). CD4/CD8 ratio was more
      or less same as healthy controls after 2 weeks. Upregulation of CD25 was
      insignificantly increased and that of HLA-DR was markedly increased after 2 weeks
      (p=0.001). Significant negative correlations were detected between mean values of
      beta2-m and both absolute numbers of CD3 and CD4 positive cells in BL and one
      week samples. In addition there was significant correlation between mean values
      of beta2-m and values of CD25 expression in the BL samples. The obtained data is
      suggestive of persistent activation of T lymphocytes two weeks after major burns
      whereas early shedding of beta2-m is related to activation of lymphocytes
      increasing their susceptibility to apoptosis, both indicative of altered immune
      response. Burn intensivists and surgeons should be keen to support the patients'
      immune system in the first hours following major burns. This support will ensure
      free-bacteremic blood with a consequent better prognosis.

PMID- 23012612
TI  - Sigmoid diverticulitis perforation in burns: case reports and review of the
      literature.
AB  - Burned patients are prone to develop severe intestinal complications because of
      decreased splanchnic circulation. We report three cases of sigmoid perforation in
      burn patients appearing late during hospitalization. The common aetiological
      factor was a state of septic shock treated with infusion of vasopressors. Two
      patients also received corticosteroids as treatment for acute respiratory
      distress syndrome. These cases underline the necessity to maintain adequate organ
      perfusion and to prevent intestinal ischaemia in severe burns.

PMID- 23012614
TI  - The use of Osmed(TM) tissue expanders in paediatric burns reconstruction.
AB  - Background. Tissue expansion has been a major advance in reconstructive burn
      surgery. The conventional tissue expander requires serial filling with the
      possibility of painful procedures, which can be a major challenge and source of
      anxiety in children. The osmotic self-inflating tissue expander, on the other
      hand, is a device that does not require external filling, offering apparent
      benefits particularly in the paediatric population. We used Osmed(TM) tissue
      expanders for secondary burn reconstruction in children and teenagers who had
      sustained burns during childhood. Methods. Patients who were treated with
      Osmed(TM) expanders for secondary burns reconstruction were recorded. Patient
      demographics (i.e. burn injury data, indications for surgery), Osmed(TM) tissue
      expander data (i.e. operative data, complications, problems encountered during
      and after treatment, explantation time, final expander volume) and overall
      success were recorded. Results. Twelve Osmed(TM) self-inflating tissue expanders
      were used in patients for secondary burns reconstruction between October 2007 and
      January 2009. All our patients sustained their burns during childhood. There were
      three females and one male; the age range was 14-19 yr (mean age, 16 yr). Tissue
      expanders were removed on average at 6-7 weeks except in two patients. We noted
      four complications in our cohort. Overall the mean expansion was 65% of the
      proposed final volume. Discussion. We found the Osmed(TM) tissue expander simple
      to implant and well tolerated by our patients. However, none of the devices
      achieved full expansion and overexpansion was not possible. We believe
      conventional tissue expanders are still the gold standard, although osmotic
      expanders may have a role in burn reconstruction in younger children.

PMID- 23012616
TI  - Acute Liver Impairment in a Young, Healthy Athlete: Hypoxic Hepatitis and
      Rhabdomyolysis following Heat Stroke.
AB  - Any process that substantially diminishes arterial blood flow or arterial oxygen
      content to the liver can result in hypoxic (ischaemic) hepatitis. 90% of hypoxic
      hepatitis occurs in unstable patients in intensive care units with haemodynamic
      failure secondary to heart failure, respiratory failure and toxic shock. The rate
      of in-hospital mortality in hypoxic hepatitis is very high with studies recording
      mortalities of 61.5%. It tends to be very uncommon in healthy, young patients
      with no underlying medical problems. We report here the case of a young healthy
      athlete who developed heat stroke associated with rhabdomyolysis and hypoxic
      hepatitis while he was running the final stages of a marathon. The patient
      required intensive care admission and inotropic support for a few hours after he
      was admitted with heat stroke. He underwent a rapid recovery after he was
      resuscitated with fluids. N-acetyl cysteine was also given during the acute stage
      of the hepatitis. This case highlights an uncommon case of hypoxic hepatitis in a
      young, healthy patient secondary to hypotension and heat stroke. Inotropic
      support might have precipitated the hypoxic hepatitis in this young patient.

PMID- 23012613
TI  - Cardiovascular dysfunction in burns: review of the literature.
AB  - Major burn injury produces substantial hemodynamic and cardiodynamic
      derangements, which contribute to the development of sepsis, multiple organ
      failure, and death. Cardiac stress is the hallmark of the acute phase response
      and its severity determines postburn outcomes, with poorer outcomes associated
      with cardiac dysfunction. With available evidence from the literature, the
      present is a comprehensive review of cardiac dysfunction in burns as well as the
      different monitoring modalities.

PMID- 23012617
TI  - Colonic mucosa-associated lymphoid tissue lymphoma.
AB  - Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are rare and a
      definitive treatment has not been established. Solitary or multiple, elevated or
      polypoid lesions are the usual appearances of MALT lymphoma in the colon and
      sometimes the surface may reveal abnormal vascularity. In this paper we report
      our experience with four cases of colonic MALT lymphoma and review the relevant
      literature. The first patient had a smooth elevated lesion in the rectum and
      histopathologic examination of the biopsy from the lesion showed centrocyte-like
      cells infiltrating the lamina propria. Endoscopic ultrasonography (EUS) revealed
      thickening of the submucosa and muscularis propria. The patient underwent
      radiation therapy, and 9 months later a repeat colonoscopy showed complete
      resolution of the lesion. In case 2, colonoscopy showed a polyp in the cecum; the
      biopsy was diagnostic of MALT lymphoma. EUS detected a hypoechoic lesion confined
      to the mucosal layer of the colonic wall. The patient underwent endoscopic
      mucosal resection of the lesion and after 6 years of follow-up there was no
      evidence of recurrence. The third patient had a sessile elevated lesion in the
      sigmoid colon for which she underwent sigmoidectomy. Pathological examination of
      the surgical specimen was suggestive of MALT lymphoma. The last patient had a
      smooth elevated lesion in the rectum and magnification endoscopy showed irregular
      vascular pattern. The patient underwent endoscopic submucosal dissection, and
      biopsy examination showed the tumor to be MALT lymphoma. Although rare, awareness
      of MALT lymphoma of the colon is important to evaluate the patient appropriately
      and to plan further management.

PMID- 23012618
TI  - Serum granulocyte colony-stimulating factor and Alzheimer's disease.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) promotes the survival
      and function of neutrophils. G-CSF is also a neurotrophic factor, increasing
      neuroplasticity and suppressing apoptosis. METHODS: We analyzed G-CSF levels in
      197 patients with probable Alzheimer's disease (AD) and 203 cognitively normal
      controls (NCs) from a longitudinal study by the Texas Alzheimer's Research and
      Care Consortium (TARCC). Data were analyzed by regression with adjustment for
      age, education, gender and APOE4 status. RESULTS: Serum G-CSF was significantly
      lower in AD patients than in NCs (beta = -0.073; p = 0.008). However, among AD
      patients, higher serum G-CSF was significantly associated with increased disease
      severity, as indicated by lower Mini-Mental State Examination scores (beta = 
      0.178; p = 0.014) and higher scores on the global Clinical Dementia Rating (CDR)
      scale (beta = 0.170; p = 0.018) and CDR Sum of Boxes (beta = 0.157; p = 0.035).
      CONCLUSIONS: G-CSF appears to have a complex relationship with AD pathogenesis
      and may reflect different pathophysiologic processes at different illness stages.

PMID- 23012620
TI  - Evaluation of the operator protection factors offered by positive pressure air
      suits against airborne microbiological challenge.
AB  - Laboratories throughout the world that perform work with Risk Group 4 Pathogens
      generally adopt one of two approaches within BSL-4 environments: either the use
      of positive pressure air-fed suits or using Class III microbiological safety
      cabinets and isolators for animal work. Within the UK at present, all
      laboratories working with Risk Group 4 agents adopt the use of Class III
      microbiological safety cabinet lines and isolators. Operator protection factors
      for the use of microbiological safety cabinets and isolators are available
      however; there is limited published data on the operator protection factors
      afforded by the use of positive pressure suits. This study evaluated the operator
      protection factors provided by positive pressure air suits against a realistic
      airborne microbiological challenge. The suits were tested, both intact and with
      their integrity compromised, on an animated mannequin within a stainless steel
      exposure chamber. The suits gave operator protection in all tests with an intact
      suit and with a cut in the leg. When compromised by a cut in the glove, a very
      small ingress of the challenge was seen as far as the wrist. This is likely to be
      due to the low airflow in the gloves of the suit. In all cases no microbiological
      penetration of the respiratory tract was observed. These data provide evidence on
      which to base safety protocols for use of positive pressure suits within high
      containment laboratories.

PMID- 23012619
TI  - Herpesvirus exploitation of host immune inhibitory pathways.
AB  - Herpesviruses employ a plethora of mechanisms to circumvent clearance by host
      immune responses. A key feature of mammalian immune systems is the employment of
      regulatory pathways that limit immune responsiveness. The primary functions of
      these mechanisms are to control autoimmunity and limit exuberant responses to
      harmless antigen in mucosal surfaces. However, such pathways can be exploited by
      viral pathogens to enable acute infection, persistence and dissemination. Herein,
      we outline the current understanding of inhibitory pathways in modulating
      antiviral immunity during herpesvirus infections in vivo and discuss strategies
      employed by herpesviruses to exploit these pathways to limit host antiviral
      immunity.

PMID- 23012621
TI  - Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of
      emergence of NVP resistance.
AB  - When HIV-1 is exposed to lamivudine (3TC) at inhibitory concentrations, resistant
      variants carrying the reverse transcriptase (RT) substitution M184V emerge
      rapidly. This substitution confers high-level 3TC resistance and increased RT
      fidelity. We established a novel in vitro system to study the effect of starting
      nevirapine (NVP) in 3TC-resistant/NNRTI-naive clinical isolates, and the impact
      of maintaining versus dropping 3TC pressure in this setting. Because M184V mutant
      HIV-1 seems hypersusceptible to adefovir (ADV), we also tested the effect of ADV
      pressure on the same isolates. We draw four conclusions from our experiments
      simulating combination therapy in vitro. (1) The presence of low-dose (1 MUM) 3TC
      prevented reversal to wild-type from an M184V mutant background. (2) Adding low
      dose 3TC in the presence of NVP delayed the selection of NVP-associated
      mutations. (3) The presence of ADV, in addition to NVP, led to more rapid
      reversal to wild-type at position 184 than NVP alone. (4) ADV plus NVP selected
      for greater numbers of mutations than NVP alone. Inference about the "selection
      of mutation" is based on two statistical models, one at the viral level, more
      telling, and the other at the level of predominance of mutation within a
      population. Multidrug pressure experiments lend understanding to mechanisms of
      HIV resistance as they bear upon new treatment strategies.

PMID- 23012623
TI  - The role of equine herpesvirus type 4 glycoprotein k in virus replication.
AB  - Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes
      respiratory tract disease among horses worldwide. Glycoprotein K (gK) homologues
      have been identified in several alphaherpesviruses as a major player in virus
      entry, replication, and spread. In the present study, EHV-4 gK-deletion mutant
      has been generated by using bacterial artificial chromosome technology and Red
      mutagenesis to investigate the role of gK in EHV-4 replication. Our findings
      reported here show that gK is essential for virus replication in vitro and that
      the gK-negative strain was not able to be reconstituted in equine cells. It is
      noteworthy that these findings agree with the previously published study
      describing gK deletion in other alphaherpesviruses.

PMID- 23012622
TI  - Updated values for molecular diagnosis for highly pathogenic avian influenza
      virus.
AB  - Highly pathogenic avian influenza (HPAI) viruses of the H5N1 strain pose a
      pandemic threat. H5N1 strain virus is extremely lethal and contagious for
      poultry. Even though mortality is 59% in infected humans, these viruses do not
      spread efficiently between humans. In 1997, an outbreak of H5N1 strain with human
      cases occurred in Hong Kong. This event highlighted the need for rapid
      identification and subtyping of influenza A viruses (IAV), not only to facilitate
      surveillance of the pandemic potential of avian IAV, but also to improve the
      control and treatment of infected patients. Molecular diagnosis has played a key
      role in the detection and typing of IAV in recent years, spurred by rapid
      advances in technologies for detection and characterization of viral RNAs and
      proteins. Such technologies, which include immunochromatography, quantitative
      real-time PCR, super high-speed real-time PCR, and isothermal DNA amplification,
      are expected to contribute to faster and easier diagnosis and typing of IAV.

PMID- 23012625
TI  - A limited structural modification results in a significantly more efficacious
      diazachrysene-based filovirus inhibitor.
AB  - Ebola (EBOV) and Marburg (MARV) filoviruses are highly infectious pathogens
      causing deadly hemorrhagic fever in humans and non-human primates. Promising
      vaccine candidates providing immunity against filoviruses have been reported.
      However, the sporadic nature and swift progression of filovirus disease
      underlines the need for the development of small molecule therapeutics providing
      immediate antiviral effects. Herein we describe a brief structural exploration of
      two previously reported diazachrysene (DAAC)-based EBOV inhibitors. Specifically,
      three analogs were prepared to examine how slight substituent modifications would
      affect inhibitory efficacy and inhibitor-mediated toxicity during not only EBOV,
      but also MARV cellular infection. Of the three analogs, one was highly
      efficacious, providing IC(50) values of 0.696 uM +/- 0.13 uM and 2.76 uM +/- 0.21
      uM against EBOV and MARV infection, respectively, with little or no associated
      cellular toxicity. Overall, the structure-activity and structure-toxicity results
      from this study provide a framework for the future development of DAAC-based
      filovirus inhibitors that will be both active and non-toxic in vivo.

PMID- 23012624
TI  - Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with
      peginterferon plus ribavirin.
AB  - It has been reported that inosine triphosphatase (ITPA) gene variants protect
      against ribavirin-induced anemia in patients treated for chronic hepatitis C.
      IL28B variants also influence the treatment response of peginterferon plus
      ribavirin treatment in these patients. In the present study, we examined how ITPA
      and IL28B genotypes have clinical impacts on treatment-induced hematotoxicities
      and treatment response in HCV-infected patients treated with peginterferon plus
      ribavirin. ITPA genotypes (rs1127354 and rs6051702) and IL28B genotype
      (rs8099917) were determined by TaqMan SNP assay. We compared clinical background,
      treatment course and treatment response in terms of these genotypes. Only IL28B
      rs8099917 major type could predict sustained virological response. ITPA rs1127354
      major type leads to significantly greater ribavirin-induced anemia than ITPA
      rs1127354 minor type between days 0 and 84. We noticed that IL28B rs8099917 minor
      genotype was associated with higher reduction of neutrophils and platelets. ITPA
      rs1127354 is useful for the prediction of ribavirin-induced anemia in the early
      phase after the commencement of peginterferon plus ribavirin treatment and IL28B
      rs8099917 is useful for the prediction of sustained virological response. Use of
      the combination of these two genotypes could lead to safe and effective treatment
      of chronic hepatitis C patients.

PMID- 23012626
TI  - Whole genomic analysis of human G1P[8] rotavirus strains from different age
      groups in China.
AB  - G1P[8] rotaviruses are an important cause of diarrhea in humans in China. To
      date, there are no reports on the whole genomic analysis of the Chinese G1P[8]
      rotaviruses. To determine the origin and overall genetic makeup of the recent
      Chinese G1P[8] strains, the whole genomes of three strains, RVA/Human
      wt/CHN/E1911/2009/G1P[8], RVA/Human-tc/CHN/R588/2005/G1P[8] and RVA/Human
      tc/CHN/Y128/2004/G1P[8], detected in an infant, a child and an adult,
      respectively, were analyzed. Strains E1911, R588 and Y128 exhibited a typical Wa
      like genotype constellation. Except for the NSP3 gene of E1911, the whole genomes
      of strains E1911, R588 and Y128 were found to be more closely related to those of
      the recent Wa-like common human strains from different countries than those of
      the prototype G1P[8] strain, or other old strains. On the other hand, the NSP3
      gene of E1911 was genetically distinct from those of Y128, R588, or other Wa-like
      common human strains, and appeared to share a common origin with those of the
      porcine-like human G9 strains, providing evidence for intergenotype reassortment
      events. Comparisons of the amino acid residues defining the VP7 and VP4 antigenic
      domains revealed several mismatches between these Chinese G1P[8] strains and the
      G1 and P[8] strains contained in the currently licensed rotavirus vaccines
      Rotarix(TM )and RotaTeq(TM).

PMID- 23012627
TI  - A review of filovirus work and facilities at the Defence Science and Technology
      Laboratory Porton Down.
AB  - Porton Down houses two separate sites capable of conducting high containment
      research on ACDP (Advisory Committee on Dangerous Pathogens) Hazard Group 4
      agents: the Defence Science and Technology Laboratory (Dstl) and the Health
      Protection Agency (HPA), and filovirus research has been performed at Porton Down
      since the first Marburg virus disease outbreak in 1967. All work is conducted
      within primary containment either within cabinet lines (for in vitro work) or
      large rigid half-suit isolators (for in vivo work). There are extensive
      aerobiological facilities at high containment and the use of these facilities
      will be reported. Research at Dstl is primarily focused on assessing and
      quantifying the hazard, and testing the efficacy of medical countermeasures
      against filoviruses. Fundamental research directed to the study and understanding
      of the infectious and pathogenic nature of the filoviruses, particularly in
      aerosols, will be reported.

PMID- 23012628
TI  - PAirwise Sequence Comparison (PASC) and its application in the classification of
      filoviruses.
AB  - PAirwise Sequence Comparison (PASC) is a tool that uses genome sequence
      similarity to help with virus classification. The PASC tool at NCBI uses two
      methods: local alignment based on BLAST and global alignment based on Needleman
      Wunsch algorithm. It works for complete genomes of viruses of several
      families/groups, and for the family of Filoviridae, it currently includes 52
      complete genomes available in GenBank. It has been shown that BLAST-based
      alignment approach works better for filoviruses, and therefore is recommended for
      establishing taxon demarcations criteria. When more genome sequences with high
      divergence become available, these demarcation will most likely become more
      precise. The tool can compare new genome sequences of filoviruses with the ones
      already in the database, and propose their taxonomic classification.

PMID- 23012629
TI  - Performance of VIDISCA-454 in feces-suspensions and serum.
AB  - Virus discovery combining sequence unbiased amplification with next generation
      sequencing is now state-of-the-art. We have previously determined that the
      performance of the unbiased amplification technique which is operational at our
      institute, VIDISCA-454, is efficient when respiratory samples are used as input.
      The performance of the assay is, however, not known for other clinical materials
      like blood or stool samples. Here, we investigated the sensitivity of VIDISCA-454
      with feces-suspensions and serum samples that are positive and that have been
      quantified for norovirus and human immunodeficiency virus type 1, respectively.
      The performance of VIDISCA-454 in serum samples was equal to its performance in
      respiratory material, with an estimated lower threshold of 1,000 viral genome
      copies. The estimated threshold in feces-suspension is around 200,000 viral
      genome copies. The decreased sensitivity in feces suspension is mainly due to
      sequences that share no recognizable identity with known sequences. Most likely
      these sequences originate from bacteria and phages which are not completely
      sequenced.

PMID- 23012630
TI  - Herpesviruses placating the unwilling host: manipulation of the MHC class II
      antigen presentation pathway.
AB  - Lifelong persistent infection by herpesviruses depends on the balance between
      host immune responses and viral immune evasion. CD4 T cells responding to
      antigens presented on major histocompatibility complex class II (MHC-II)
      molecules are known to play an important role in controlling herpesvirus
      infections. Here we review, with emphasis on human herpesvirus infections, the
      strategies evolved to evade CD4 T cell immunity. These viruses target multiple
      points on the MHC class II antigen presentation pathway. The mechanisms include:
      suppression of CIITA to inhibit the synthesis of MHC class II molecules,
      diversion or degradation of HLA-DR molecules during membrane transport, and
      direct targeting of the invariant chain chaperone of HLA-DR.

PMID- 23012632
TI  - Diurnal variations in physical performances related to football in young soccer
      players.
AB  - PURPOSE: This study investigated the effects of time-of-day on aerobic and
      anaerobic performances during the Yo-Yo, repeated sprint ability (RSA) and the
      Wingate tests in young soccer players. METHODS: In a counterbalanced and a random
      order, twenty junior male soccer players completed the Yo-Yo, the RSA, and the
      Wingate tests at two different times-of-day: 07:00 and 17:00 h. During the Yo-Yo
      test, the total distance (TD) covered and the estimated maximal aerobic velocity
      (MAV) were determined. The peak power (PP) during each sprint, the percentage of
      decrement of PP (PD) and total work (Wtotal) during the RSA test were, also,
      measured. In addition, during the Wingate test, the peak (P(peak)) and mean
      (P(mean)) powers were recorded. RESULTS: During the Wingate test, P(peak) and
      P(mean) were significantly higher at 17:00 than 07:00 h (P<0.05) with diurnal
      gains of 3.1+/-3.6 and 2.9+/-3.5% respectively. During the RSA test, PP during
      the first two sprints, Pdec and Wtotal were, also, higher in the evening (P<0.05)
      with amplitudes of 4.8+/-4.6, 3.1+/-3.0, 13.1+/-32.1, and 4.1+/-2.5%
      respectively. Likewise, TD and MAV during the Yo-Yo test were higher at 17:00
      than 07:00 h with diurnal gains of 13.1+/-10.7 and 4.2+/-3.3 respectively.
      CONCLUSIONS: The present study confirms the daily variations of both aerobic and
      anaerobic performances during the Yo-Yo, the RSA, and the Wingate tests in
      trained young Tunisian soccer players.

PMID- 23012631
TI  - Shedding light on filovirus infection with high-content imaging.
AB  - Microscopy has been instrumental in the discovery and characterization of
      microorganisms. Major advances in high-throughput fluorescence microscopy and
      automated, high-content image analysis tools are paving the way to the systematic
      and quantitative study of the molecular properties of cellular systems, both at
      the population and at the single-cell level. High-Content Imaging (HCI) has been
      used to characterize host-virus interactions in genome-wide reverse genetic
      screens and to identify novel cellular factors implicated in the binding, entry,
      replication and egress of several pathogenic viruses. Here we present an overview
      of the most significant applications of HCI in the context of the cell biology of
      filovirus infection. HCI assays have been recently implemented to quantitatively
      study filoviruses in cell culture, employing either infectious viruses in a BSL-4
      environment or surrogate genetic systems in a BSL-2 environment. These assays are
      becoming instrumental for small molecule and siRNA screens aimed at the discovery
      of both cellular therapeutic targets and of compounds with anti-viral properties.
      We discuss the current practical constraints limiting the implementation of high
      throughput biology in a BSL-4 environment, and propose possible solutions to
      safely perform high-content, high-throughput filovirus infection assays. Finally,
      we discuss possible novel applications of HCI in the context of filovirus
      research with particular emphasis on the identification of possible cellular
      biomarkers of virus infection.

PMID- 23012633
TI  - Participation and Performance Trends in Triple Iron Ultra-triathlon - a Cross
      sectional and Longitudinal Data Analysis.
AB  - PURPOSE: The aims of the present study were to investigate (i) the changes in
      participation and performance and (ii) the gender difference in Triple Iron ultra
      triathlon (11.4 km swimming, 540 km cycling and 126.6 km running) across years
      from 1988 to 2011. METHODS: For the cross-sectional data analysis, the
      association between with overall race times and split times was investigated
      using simple linear regression analyses and analysis of variance. For the
      longitudinal data analysis, the changes in race times for the five men and women
      with the highest number of participations were analysed using simple linear
      regression analyses. RESULTS: During the studied period, the number of finishers
      were 824 (71.4%) for men and 80 (78.4%) for women. Participation increased for
      men (r(2)=0.27, P<0.01) while it remained stable for women (8%). Total race times
      were 2,146 +/- 127.3 min for men and 2,615 +/- 327.2 min for women (P<0.001).
      Total race time decreased for men (r(2)=0.17; P=0.043), while it increased for
      women (r(2)=0.49; P=0.001) across years. The gender difference in overall race
      time for winners increased from 10% in 1992 to 42% in 2011 (r(2)=0.63; P<0.001).
      The longitudinal analysis of the five women and five men with the highest number
      of participations showed that performance decreased in one female (r(2)=0.45;
      P=0.01). The four other women as well as all five men showed no change in overall
      race times across years. CONCLUSIONS: Participation increased and performance
      improved for male Triple Iron ultra-triathletes while participation remained
      unchanged and performance decreased for females between 1988 and 2011. The
      reasons for the increase of the gap between female and male Triple Iron ultra
      triathletes need further investigations.

PMID- 23012634
TI  - Acute injuries in student circus artists with regard to gender specific
      differences.
AB  - PURPOSE: Student circus artists train as both artists and athletes with their
      bodies holding the key to professional success. The daily training load of
      student circus artists is often associated with maximum physical and
      psychological stress with injuries posing a threat to a potential professional
      career. The purpose of this study is the differentiated analysis and evaluation
      of work accidents in order to initiate the development of injury preventive
      programs. METHODS: The 17 years of data were obtained from standardized anonymous
      work accident records of the Berlin State Accident Insurance (UKB) as well as a
      State Artist Educational School (n = 169, Male: 70; Female: 99) from student
      artists. Evaluation and descriptive statistics were conducted with Excel 2007 and
      PASW Statistics 18. RESULTS: The injury risk seems to be relatively low (0.3
      injuries/1000h). There are gender specific differences as to the location of
      injuries. Only 7% of the accidents demand a break of more than 3 days. Injury
      patterns vary depending on the activity and the employment of props/equipment.
      75.2% of work accidents have multifactorial and 24.8% exogenous causes.
      CONCLUSIONS: Because physical fitness is all important in the circus arts there
      are numerous options for injury prevention programs that should be realized
      subject to gender-specific differences. Follow-ups on chronic complaints and a
      more individual approach are indispensable due to the very specific activities in
      the circus arts.

PMID- 23012635
TI  - Effects of morning caffeine' ingestion on mood States, simple reaction time, and
      short-term maximal performance on elite judoists.
AB  - PURPOSE: The purpose of the present study was to evaluate the ergogenic effect of
      caffeine ingestion on mood state, simple reaction time, and muscle power during
      the Wingate test recorded in the morning on elite Judoists. METHODS: TWELVE ELITE
      JUDOISTS (AGE: 21.08 +/- 1.16 years, body mass: 83.75 +/- 20.2 kg, height: 1.76
      +/-6.57 m) participated in this study. Mood states, simple reaction time, and
      muscle power during the Wingate test were measured during two test sessions at
      07:00 h and after placebo or caffeine ingestion (i.e. 5 mg/kg). Plasma
      concentrations of caffeine were measured before (T0) and 1-h after caffeine'
      ingestion (T1) and after the Wingate test (T3). RESULTS: Our results revealed an
      increase of the anxiety and the vigor (P<0.01), a reduction of the simple
      reaction time (P<0.001) and an improvement of the peak and mean powers during the
      Wingate test. However, the fatigue index during this test was unaffected by the
      caffeine ingestion. In addition, plasma concentration of caffeine was
      significantly higher at T1 in comparison with T0. CONCLUSIONS: In conclusion, the
      results of this study suggest that morning caffeine ingestion has ergogenic
      properties with the potential to benefit performance, increase anxiety and vigor,
      and decrease the simple reaction time.

PMID- 23012636
TI  - Elevated body mass index and body fat percentage are associated with decreased
      physical fitness in soccer players aged 12-14 years.
AB  - PURPOSE: Adolescents are in increased risk for the development of obesity, while
      sport has been suggested as an effective means against adolescent obesity. The
      objectives of this study were to examine (a) the prevalence of
      overweightness/obesity, (b) the relationship between body mass index (BMI) and
      body fat percent (BF), and (c) the association between BMI, BF and physical
      fitness in adolescent soccer players. METHODS: Members (n=136, aged 13.1+/-0.6
      yr) of competitive soccer clubs were examined for physical and physiological
      characteristics. RESULTS: Based on international BMI cut-off points, 19.9% (n=27)
      of participants were classified as overweight. BMI was highly correlated with BF
      (r=0.77, P<0.001). BMI and BF were in inverse relationship with aerobic power (r=
      - 0.29, P<0.001; r= - 0.44, P<0.001, respectively), maximal anaerobic power (r= -
      0.23, P=0.009; r= - 0.47, P<0.001) and local muscular endurance (r= - 0.36,
      P<0.001; r= - 0.67, P<0.001). CONCLUSIONS: The strong relationship between BMI
      and BF suggest the further use of BMI in adolescent soccer players. The findings
      confirmed previous observations in the general population about the negative
      effect of overweight and fatness on physical fitness. The prevalence of
      overweightness among participants was similar with what is observed in general
      population. Therefore, sport participation cannot guarantee physiological body
      mass and body composition, and it is necessary to prescribe exercise targeting
      body mass and fat control.

PMID- 23012637
TI  - Monitoring training load and fatigue in rugby sevens players.
AB  - PURPOSE: Trainers and physical fitness coaches' need a useful tool to assess
      training loads to avoid overtraining. However, perceived scales or questionnaires
      were required. Therefore, the purpose of this study was to assess whether a short
      8-item questionnaire of fatigue could be a useful tool for monitoring changes in
      perceived training load and strain among elite rugby Sevens (7s) players during
      preparation for a major competition. METHODS: Sixteen elite rugby 7s players
      completed an 8-week training program composed of 6-week intense training (IT) and
      2-week reduced training (RT). They were tested before (T0), after the IT (T1) and
      after the RT (T2). The quantification of the perceived training load and strain
      were performed by the session-RPE (rating of perceived exertion) method and
      concomitantly the 8-item questionnaire of fatigue was administered. RESULTS:
      Training load (TL) and strain (TS) and total score of fatigue (TSF from the 8
      item questionnaire) increased during IT and decreased during RT. Simultaneously,
      physical performances decreased during IT and were improved after LT. The changes
      in TL, TS and TSF correlated significantly over the training period (r=0.63
      0.83). CONCLUSIONS: These findings suggest that the short questionnaire of
      fatigue could be a practical and a sensitive tool for monitoring changes in
      training load and strain in team-sport athletes. Accordingly, the simultaneous
      use of the short questionnaire of fatigue along with the session-RPE method for
      perceived changes in training load and strain during training could provide
      additional information on the athletes' status, allowing coaches to prevent
      eventual states of overreaching or overtraining.

PMID- 23012638
TI  - Influence of selected exercise on serum immunoglobulin, testosterone and cortisol
      in semi-endurance elite runners.
AB  - PURPOSE: The aim of this study was to compare the levels of serum immunoglobulin
      (IgA, IgM, IgG), testosterone and cortisol in semi-endurance elite runners during
      general preparation and competition phase of training. METHODS: Thirteen semi
      endurance elite male runners with an average age of 18.92+/-1.7 years volunteered
      to take part in this study. The runners participated in the selected training for
      a period of 14 weeks and 12 sessions per week (in the morning and afternoon).
      Blood samples were collected during the three phases of training (before
      preparation phase, after-preparation phase and before-competition phase). Data
      were analyzed by repeated measures and Bonferroni post hoc test, at a
      significance level of P<0.05. RESULTS: The levels of serum IgM in semi-endurance
      elite runners after preparation phase reduced significantly (P=0.004), while
      these levels during the competition phase increased even though significantly.
      The levels of serum IgG and IgA also reduced, however not significantly, during
      both phases. Moreover, after preparation phase, there was no significant change
      in serum IgA levels; though, these levels reduced, however not significantly,
      before competition phase. Cortisol levels significantly decrease after
      preparation phase (P=0.04); although, it increased before competition phase.
      Testosterone/cortisol ratio increases significantly after preparation phase
      (P=0.04), and it decreased before competition phase. Testosterone levels
      intangibility increased and decreased respectively after preparation and before
      competition phases. CONCLUSIONS: Findings indicated that long and intensive
      exercises weaken the immune system, while moderate and short drills strengthened
      this system.

PMID- 23012639
TI  - Effect of Exercise Program and Calcium Supplements on Low Bone Mass among Young
      Indian Women- A Comparative Study.
AB  - PURPOSE: Low bone mass is a major health concern among young women nowadays due
      to sedentary lifestyle and lack of calcium rich food intake. Therefore there is
      an increase in the incidence of LBM among young university women so our main
      purpose of study was to compare effects of exercise program and calcium
      supplements on bone mass in young women. METHODS: This single blinded, cross
      sectional study included data collection in the form of SOS T-scores at distal
      radius for 104 young university women of mean age 22.3 years using Sunlight
      Omnisense Bone Sonometer 7000S. Of these, 62 women with low bone mass were
      included in a 3 month study but 60 subjects completed the study. They were
      randomly divided into 3 groups: exercise group (n=21), calcium supplementation
      group (n=21) and control group (n=20). All participants were evaluated pre and
      post protocol for T-score distal radius and midshaft tibia. RESULTS: After
      measuring SOS T-score of 104 subjects; we found that 60.57% had low bone mass and
      remaining 39.43% had normal bone mass. After 3 months, the exercise group showed
      significant improvement in distal radius SOS T-score (t=5.10, P<0.001), at
      midshaft tibia (t=3.71, P<0.001) followed by improvement in calcium group at
      distal radius (t=6.28, P<0.001), midshaft tibia (t=2.33, P<0.05) as compared to
      control group which showed a marginal increase. CONCLUSIONS: Exercise group
      showed more improvement in T-scores than calcium and control group. Exercise is
      important modifiable factor to improve bone accretion at this age and reduce risk
      of developing osteoporosis related debilitating conditions later in life.

PMID- 23012640
TI  - The estimation of the fat free mass index in athletes.
AB  - PURPOSE: The purpose of this investigation was to compare a practical measurement
      of fat free mass index (FFMI) from bioelectrical impedance analysis (BIA) to the
      dual energy X-ray absorptiometry (DEXA) value in collegiate athletes. METHODS:
      Thirty-three male baseball players and 16 female gymnasts volunteered to
      participate in this study during their respective pre-season. Subjects visited
      the laboratory once and had their measurements taken in the following order:
      weight, height, DEXA, and Omron HBF-500. RESULTS: The BIA device investigated was
      not a valid estimate of FFMI when compared to the DEXA. The TE was 0.93 kg/ m(2)
      for males and 0.78 kg/ m(2) for females. There were also significant mean
      differences between the BIA prediction and the DEXA value for males (BIA=20.6
      kg/m(2) vs. DEXA=21.1 kg/m(2), P=0.007) and females (BIA=16.2 kg/m(2) vs.
      DEXA=17.5 kg/m(2), P=0.001). CONCLUSIONS: The BIA device investigated in this
      study did not provide a valid estimate of FFMI in male and female collegiate
      athletes. Although there was a general tendency for the BIA to underestimate FFMI
      compared to DEXA, 98% of the estimates were within plus or minus 2 kg/ m(2).
      Therefore, while slightly biased, BIA may provide a reasonable (+/- 2 kg/ m(2))
      estimate of nutritional status for practitioners who are unable able to afford
      more expensive equipment.

PMID- 23012641
TI  - Health-related quality of life in Iranian women with different levels of physical
      activity.
AB  - PURPOSE: One of the most significant current discussions is the effect of
      different levels of physical activity on health-related quality of life (HRQOL),
      but there have been no studies in Iran which investigate this issue. The aim of
      this study was to investigate the relationship between the level of physical
      activity and HRQOL in Iranian women. METHODS: This was an analytical cross
      sectional study conducted from October 2010 to January 2011 in Karaj's
      gymnasiums. We selected gymnasiums using simple randomized sampling. The
      validated Persian short form 36-item HRQOL questionnaire version 2.0 (SF-36 v2)
      and the short form of the International Physical Activity Questionnaire were used
      for data collection. Based on IPAQ, participants were classified into two groups:
      one with a high level of physical activity (N=240) and another with a moderate
      level (N = 120). RESULTS: The group with a high level of physical activity had
      significantly higher vitality scores (P=0.01) and lower role limitation-physical
      scores (P=0.02) than the group with a moderate level. The high level of physical
      activity was associated with considerably higher scores in general health (73.94
      +/- 0.99 vs.70.82 +/- 1.33) (P=0.06) and mental well-being (73.94 +/- 1.18
      vs.70.88 +/- 1.82) (P=0.1) domains than moderate level. CONCLUSIONS: It seems
      that the high level of physical activity, compared with the moderate level, tends
      to have positive association with more domains of SF-36 v2.

PMID- 23012642
TI  - Congenital Adrenal Hyperplasia in an Elite Female Soccer Player; What Sports
      Medicine Clinicians Should Know about This?
AB  - BACKGROUND: Congenital Adrenal Hyperplasia (CAH) refers to a group of congenital
      conditions characterized by disordered cortisol synthesis. The correlation
      between CAH and sports performance has been less studied before and there is very
      limited information regarding the impacts of this congenital disease on sports
      performance. Probably, there are some limitations for patients who suffer from
      CAH in sports, but at the same time, they may enjoy some advantage due to the
      probable effect of endogenous hyperandrogenism on their exercise performance.
      CASE PRESENTATION: The case is a 14 - year old girl with male phenotype who is a
      known case of congenital adrenal hyperplasia. She plays in the women's national
      soccer team of under 16. She has been in the first division league of indoor
      soccer for 4 years and was also selected in the preparation training camp of
      women's football team for Singapore's youth Olympic Games. Her illness and
      dependence on corticosteroid have caused some concerns for her participation in
      the international competitions of women. However, following consultations with
      the Therapeutic Use Exemption (TUE) Committee of games organization, she received
      TUE to use corticosteroid only within the games period. Despite all her problems,
      she is now playing in the Second Division League of indoor soccer. CONCLUSIONS: A
      female adolescent with CAH may compete at the high level of outdoor and indoor
      soccer. However, there are many questions regarding the advantages and
      disadvantages of this congenital disorder and its treatment on sports related
      issues.

PMID- 23012643
TI  - Knee pain following a ski injury.
AB  - CASE: A 13-year-old boy presented to the ski clinic following a fall and a
      possible twisting of his right knee. He was not able to bear any weight on his
      right leg and was experiencing pain in the medial aspect of his right knee. His
      past medical and surgical histories were unremarkable and he was otherwise in
      good health. Physical examination revealed no ecchymosis or effusion. He had
      moderate tenderness over the medial femoral condyle. Stress valgus test did not
      reveal any laxity, but caused significant pain. Plain radiography was performed
      (Fig. 1). How do you interpret his radiographs?Enchondroma of the medial distal
      femur.Nonossifying fibroma of the medial distal femur.Osteoid osteoma of the
      medial distal femur.Salter-Harris type II fracture of the distal femur.

PMID- 23012644
TI  - Travelling fellowship program for football medicine; report on an experience.
AB  - Football medicine has developed in the world in recent years. AFC Medical
      Committee, established the idea of football medicine travelling fellowship two
      years ago and provided high-level healthcare services to football players in
      Asian countries. This is a report on my one month experience in a travelling
      fellowship program for football medicine which is attempting to tell the reader
      about the interesting event that I experienced. This course has been held between
      Jan 15 to Feb 10, 2012 in 3 Asian countries: Qatar, Thailand and Malysia. The
      experience provided me with the valuable suggestions for future travelling
      fellowship periods.

PMID- 23012645
TI  - N-type graphene induced by dissociative H2 adsorption at room temperature.
AB  - Studies of the interaction between hydrogen and graphene have been increasingly
      required due to the indispensable modulation of the electronic structure of
      graphene for device applications and the possibility of using graphene as a
      hydrogen storage material. Here, we report on the behaviour of molecular hydrogen
      on graphene using the gate voltage-dependent resistance of single-, bi-, and
      multi-layer graphene sheets as a function of H2 gas pressure up to 24 bar from
      300 K to 345 K. Upon H2 exposure, the charge neutrality point shifts toward the
      negative gate voltage region, indicating n-type doping, and distinct Raman
      signature changes, increases in the interlayer distance of multi-layer graphene,
      and a decrease in the d-spacing occur, as determined by TEM. These results
      demonstrate the occurrence of dissociative H2 adsorption due to the existence of
      vacancy defects on graphene.

PMID- 23012646
TI  - Spatial filter based bessel-like beam for improved penetration depth imaging in
      fluorescence microscopy.
AB  - Monitoring and visualizing specimens at a large penetration depth is a challenge.
      At depths of hundreds of microns, several physical effects (such as, scattering,
      PSF distortion and noise) deteriorate the image quality and prohibit a detailed
      study of key biological phenomena. In this study, we use a Bessel-like beam in
      conjugation with an orthogonal detection system to achieve depth imaging. A
      Bessel-like penetrating diffractionless beam is generated by engineering the back
      aperture of the excitation objective. The proposed excitation scheme allows
      continuous scanning by simply translating the detection PSF. This type of imaging
      system is beneficial for obtaining depth information from any desired specimen
      layer, including nano-particle tracking in thick tissue. As demonstrated by
      imaging the fluorescent polymer-tagged-CaCO3 particles and yeast cells in a
      tissue-like gel-matrix, the system offers a penetration depth that extends up to
      650 um. This achievement will advance the field of fluorescence imaging and deep
      nano-particle tracking.

PMID- 23012647
TI  - Importance of beta-Catenin in glucose and energy homeostasis.
AB  - In settings of increased insulin demand, failure to expand pancreatic beta-cells
      mass leads to diabetes. Genome-wide scans of diabetic populations have uncovered
      several genes associated with susceptibility to type 2 diabetes and a number of
      them are part of the Wnt signaling. beta-Catenin, a Wnt downstream effector
      participates in pancreatic development, however, little is known about its action
      in mature beta-cells. Deletion of beta-Catenin in Pdx1 pancreatic progenitors
      leads to a decreased beta-cell mass and impaired glucose tolerance. Surprisingly,
      loss of beta-catenin made these mice resistant to high fat diet because of their
      increased energy expenditure and insulin sensitivity due to hyperactivity. The
      complexity of this phenotype was also explained in part by ectopic expression of
      Cre recombinase in the hypothalamus. Our data implicates beta-Catenin in the
      regulation of metabolism and energy homeostasis and suggest that Wnt signaling
      modulates the susceptibility to diabetes by acting on different tissues.

PMID- 23012648
TI  - The efficacy of musical emotions provoked by Mozart's music for the
      reconciliation of cognitive dissonance.
AB  - Debates on the origin and function of music have a long history. While some
      scientists argue that music itself plays no adaptive role in human evolution,
      others suggest that music clearly has an evolutionary role, and point to music's
      universality. A recent hypothesis suggested that a fundamental function of music
      has been to help mitigating cognitive dissonance, which is a discomfort caused by
      holding conflicting cognitions simultaneously. It usually leads to devaluation of
      conflicting knowledge. Here we provide experimental confirmation of this
      hypothesis using a classical paradigm known to create cognitive dissonance.
      Results of our experiment reveal that the exposure to Mozart's music exerted a
      strongly positive influence upon the performance of young children and served as
      basis by which they were enabled to reconcile the cognitive dissonance.

PMID- 23012649
TI  - Molecular motions as a drug target: mechanistic simulations of anthrax toxin
      edema factor function led to the discovery of novel allosteric inhibitors.
AB  - Edema Factor (EF) is a component of Bacillus anthracis toxin essential for
      virulence. Its adenylyl cyclase activity is induced by complexation with the
      ubiquitous eukaryotic cellular protein, calmodulin (CaM). EF and its complexes
      with CaM, nucleotides and/or ions, have been extensively characterized by X-ray
      crystallography. Those structural data allowed molecular simulations analysis of
      various aspects of EF action mechanism, including the delineation of EF and CaM
      domains through their association energetics, the impact of calcium binding on
      CaM, and the role of catalytic site ions. Furthermore, a transition path
      connecting the free inactive form to the CaM-complexed active form of EF was
      built to model the activation mechanism in an attempt to define an inhibition
      strategy. The cavities at the surface of EF were determined for each path
      intermediate to identify potential sites where the binding of a ligand could
      block activation. A non-catalytic cavity (allosteric) was found to shrink rapidly
      at early stages of the path and was chosen to perform virtual screening. Amongst
      18 compounds selected in silico and tested in an enzymatic assay, 6 thiophen
      ureidoacid derivatives formed a new family of EF allosteric inhibitors with IC50
      as low as 2 micromolars.

PMID- 23012650
TI  - Botulinum Neurotoxin A injections influence stretching of the gastrocnemius
      muscle-tendon unit in an animal model.
AB  - Botulinum Neurotoxin A (BoNT-A) injections have been used for the treatment of
      muscle contractures and spasticity. This study assessed the influence of (BoNT-A)
      injections on passive biomechanical properties of the muscle-tendon unit.
      Mousegastrocnemius muscle (GC) was injected with BoNT-A (n = 18) or normal saline
      (n = 18) and passive, non-destructive, in vivo load relaxation experimentation
      was performed to examine how the muscle-tendon unit behaves after chemical
      denervation with BoNT-A. Injection of BoNT-A impaired passive muscle recovery
      (15% vs. 35% recovery to pre-stretching baseline, p < 0.05) and decreased GC
      stiffness (0.531 +/- 0.061 N/mm vs. 0.780 +/- 0.037 N/mm, p < 0.05) compared to
      saline controls. The successful use of BoNT-A injections as an adjunct to
      physical therapy may be in part attributed to the disruption of the stretch
      reflex; thereby modulating in vivo passive muscle properties. However, it is also
      possible that BoNT-A injection may alter the structure of skeletal muscle; thus
      modulating the in vivo passive biomechanical properties of the muscle-tendon
      unit.

PMID- 23012652
TI  - Peptide-binding domains: are limp handshakes safest?
AB  - Interactions between short peptides within proteins and peptide-binding domains
      can trigger many important cell signaling processes, and their interactions are
      typically of modest affinity. A study showed that this modest affinity appears to
      be favored by evolution. They used phage display selection to discover
      "superbinder" Src Homology 2 (SH2) domains, which bound peptides with much
      stronger affinity than naturally occurring SH2 domains. These superbinder domains
      had strong biological effects, such as blocking cell signaling. Although the
      superbinders had higher affinity, this did not appear to reduce their
      specificity. In contrast, SH2-binding peptides from bacterial pathogens have
      evolved to exhibit promiscuity of binding to multiple SH2 domains, carried within
      effector proteins that subvert signaling upon entry into the mammalian cell.
      Because there are many potential peptide binders of the SH2 domain found in
      numerous human proteins, modest affinity not only may optimize transient
      signaling mediated by reversible interactions but also may minimize off-target
      deleterious binding effects. The stage is set for a more thorough evaluation of
      the specificity and off-target impact of both naturally occurring and artificial
      domains and peptides. This may help define both targets and reagents for
      therapeutic intervention in key signaling processes mediated by short peptides.

PMID- 23012651
TI  - Animal toxins can alter the function of Nav1.8 and Nav1.9.
AB  - Human voltage-activated sodium (Nav) channels are adept at rapidly transmitting
      electrical signals across long distances in various excitable tissues. As such,
      they are amongst the most widely targeted ion channels by drugs and animal
      toxins. Of the nine isoforms, Nav1.8 and Nav1.9 are preferentially expressed in
      DRG neurons where they are thought to play an important role in pain signaling.
      Although the functional properties of Nav1.8 have been relatively well
      characterized, difficulties with expressing Nav1.9 in established heterologous
      systems limit our understanding of the gating properties and toxin pharmacology
      of this particular isoform. This review summarizes our current knowledge of the
      role of Nav1.8 and Nav1.9 in pain perception and elaborates on the approaches
      used to identify molecules capable of influencing their function.

PMID- 23012653
TI  - Where EGF receptors transmit their signals.
AB  - Excessive signaling by receptor tyrosine kinases (RTKs) can cause cancer. What
      molecular mechanisms normally control RTK signaling? Are they defective in
      tumors? If so, should therapeutics be developed to restore particular regulatory
      pathways to cancer cells? These questions have been approached through
      mechanistic studies of a prototypical RTK, the epidermal growth factor receptor
      (EGFR). EGFR signaling is mediated and regulated by both signaling and
      trafficking effectors. The amplitude of receptor-proximal signals changes as
      EGFRs move along the degradative trafficking pathway from the cell surface, to
      endosomes, and into lysosomes. To optimize therapeutic suppression of receptor
      oncogenicity, it may be crucial to target EGFRs that are signaling from a
      specific site in the trafficking pathway. Research suggests that EGFRs at the
      plasma membrane produce the bulk of the global transcriptional response to EGF.
      EGFRs localized between the internalization and early endosome fusion stages of
      the pathway enrich the expression of transcripts associated with cancer. EGFRs at
      later trafficking checkpoints controlled by the endosomal sorting complex
      required for transport (ESCRT) complexes II and III do not contribute
      substantially to the EGFR-mediated transcriptional response. These results
      suggest that therapeutics targeting the receptors at the earliest stages of
      degradative trafficking might be most effective.

PMID- 23012654
TI  - Cell responses to growth factors: the role of receptor tyrosine kinase
      intracellular domain fragments.
AB  - Growth factor activation of receptor tyrosine kinases (RTKs) provokes well
      described canonical second messenger pathways that transmit biochemical signals
      in the cytoplasm and to the nucleus to initiate cellular responses. The
      proteolytic liberation of intracellular domain fragments (ICDs) from activated
      RTKs and the nuclear translocation of these ICDs represent a more recently
      identified and noncanonical mechanism by which RTKs communicate with the nucleus.
      Several reports have added previously unknown facets to the ICD mechanism and
      have enlarged the scope of ICDs as second messengers.

PMID- 23012655
TI  - Superbinder SH2 domains act as antagonists of cell signaling.
AB  - Protein-ligand interactions mediated by modular domains, which often play
      important roles in regulating cellular functions, are generally of moderate
      affinities. We examined the Src homology 2 (SH2) domain, a modular domain that
      recognizes phosphorylated tyrosine (pTyr) residues, to investigate how the
      binding affinity of a modular domain for its ligand influences the structure and
      cellular function of the protein. We used the phage display method to perform
      directed evolution of the pTyr-binding residues in the SH2 domain of the tyrosine
      kinase Fyn and identified three amino acid substitutions that critically affected
      binding. We generated three SH2 domain triple-point mutants that were
      "superbinders" with much higher affinities for pTyr-containing peptides than the
      natural domain. Crystallographic analysis of one of these superbinders revealed
      that the superbinder SH2 domain recognized the pTyr moiety in a bipartite binding
      mode: A hydrophobic surface encompassed the phenyl ring, and a positively charged
      site engaged the phosphate. When expressed in mammalian cells, the superbinder
      SH2 domains blocked epidermal growth factor receptor signaling and inhibited
      anchorage-independent cell proliferation, suggesting that pTyr superbinders might
      be explored for therapeutic applications and useful as biological research tools.
      Although the SH2 domain fold can support much higher affinity for its ligand than
      is observed in nature, our results suggest that natural SH2 domains are not
      optimized for ligand binding but for specificity and flexibility, which are
      likely properties important for their function in signaling and regulatory
      processes.

PMID- 23012656
TI  - Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination
      and the extent of myelination during development.
AB  - Schwann cells respond to cues from axons by transforming their cellular
      morphology and forming myelin. We demonstrated that the guanine nucleotide
      exchange factor (GEF) cytohesin-1 promoted myelination by activating the small
      guanosine triphosphatase (GTPase) Arf6. In mice, ablating cytohesin-1 delayed
      myelination and diminished the amount of myelin produced. We determined that the
      Src-family kinase Fyn phosphorylated tyrosine 382 (Y(382)) of cytohesin-1, and we
      generated transgenic mice that expressed a Schwann cell-specific phosphorylation
      mutant of cytohesin-1 (Y382F) that could not be targeted by Fyn. During
      development, these transgenic mice displayed delayed myelination compared to that
      of wild-type mice, as well as a decrease in the amount of myelin produced,
      similar to that observed in cytohesin-1-/- mice. These findings demonstrate that
      phosphorylation of cytohesin-1 by Fyn is required for full myelination and
      suggest that tyrosine phosphorylation of GEFs may be a mechanism to activate
      small GTPases engaged in cell morphogenesis.

PMID- 23012657
TI  - The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in
      recipient cells.
AB  - Exosomes are microvesicles of endosomal origin that are secreted, and their
      contents (proteins, lipids, DNA, or microRNAs) can alter the physiological states
      of recipient cells. We demonstrated that phosphatase and tensin homolog deleted
      on chromosome 10 (PTEN), a tumor suppressor protein normally localized in the
      cytoplasm and nucleus, was secreted in exosomes. Secreted PTEN was internalized
      by recipient cells with resultant functional activity, which resulted in reduced
      phosphorylation of the serine and threonine kinase Akt and reduced cellular
      proliferation. PTEN secretion in exosomes required Ndfip1, an adaptor protein for
      members of the Nedd4 family of E3 ubiquitin ligases. Without Ndfip1, neither
      Nedd4-1 nor Nedd4-2 promoted the recruitment of PTEN into exosomes. In addition,
      lysine 13 within PTEN, which is required for its ubiquitination by Nedd4-1, was
      required for exosomal transport of PTEN. These results implicate Ndfip1 as a
      molecular regulator of the exosomal export of PTEN, with consequences for non
      cell-autonomous PTEN activity. Thus, we suggest that the ability of PTEN to exert
      phosphatase activity beyond the cell in which it is produced has implications for
      PTEN function during development, health, and disease.

PMID- 23012658
TI  - Silicone gel breast implants at 50: the state of the science.

PMID- 23012659
TI  - Facial bone density: effects of aging and impact on facial rejuvenation.
AB  - BACKGROUND: Facial bone aging has recently been described as primarily resulting
      from volume loss and morphologic changes to the orbit, midface, and mandible.
      OBJECTIVE: The authors demonstrate how the facial skeleton bone mineral density
      (BMD) changes with age in both men and women and compare these changes to those
      of the axial skeleton. They also explore the aesthetic implications of such
      changes in bone density. METHODS: Dual-energy X-ray absorptiometry (DXA) scans of
      the facial bones and lumbar spine were obtained from 60 white subjects, 30 women
      and 30 men. There were 10 men and 10 women in each of 3 age categories: young (20
      40 years), middle (41-60 years), and old (61+ years). The following measurements
      were obtained: lumbar spine BMD (average BMD of L1-L4 vertebrae), maxilla BMD
      (the average BMD of the right and left maxilla), and mandible BMD (the average
      BMD of the right and left mandibular ramus). RESULTS: The lumbar spine BMD
      decreased significantly for both sexes between the middle and old age groups.
      There was a significant decrease in the maxilla and mandible BMD for both sexes
      between the young and middle age groups. CONCLUSIONS: Our results suggest that
      the BMD of the face changes with age, similar to the axial skeleton. This change
      in BMD may contribute to the appearance of the aging face and potentially affect
      facial rejuvenation procedures.

PMID- 23012660
TI  - Incidental association of a hepatic vascular tumor.

PMID- 23012661
TI  - Small bowel splenule mimicking a gastrointestinal stromal tumor.

PMID- 23012663
TI  - WGO digestive oncology task force: validation of hepatogastroenterologist
      practice in oncology.

PMID- 23012662
TI  - Mucinous adenocarcinoma arising from diffuse serrated adenoma of the appendix
      which mimics appendicular abscess.

PMID- 23012664
TI  - Association of genetic polymorphisms in IL17A and IL17F with gastro-duodenal
      diseases.
AB  - BACKGROUND & AIM: The important role of IL-17 in inflammatory response to
      Helicobacter pylori (H. pylori) colonization has been indicated. We investigated
      the associations between gastro-duodenal diseases and polymorphisms of IL17A
      (rs2275913 G>A) and IL17F (rs763780 T>C). METHODS: The study was performed in 548
      subjects (363 controls and 185 peptic ulcer cases). The multiplex PCR-SSCP method
      was used to detect gene polymorphisms. RESULTS: Overall, number of rs2275913 A
      allele was significantly associated with an increased risk for peptic ulcer (OR,
      1.50; 95%CI, 1.11-2.01; p=0.0082). The frequency of rs2275913 GA+AA genotype was
      also significantly higher in ulcer cases than controls (OR, 1.72; 95%CI, 1.09
      2.72; p=0.020). The rs2275913 GA+AA genotype conferred an increased risk for the
      severity of gastric mucosal atrophy in subjects younger than 60 years (OR, 2.83;
      95%CI, 1.14-7.04; p=0.025). Both atrophy and metaplasia were increased with age
      in rs2275913 GA+AA genotype. In NSAIDs/aspirin users, number of rs2275913 A
      allele was associated with an increased risk for a peptic ulcer (OR, 3.98; 95%CI,
      1.48-10.7; p=0.0061). There was no association of rs763780 with the development
      of peptic ulcer. CONCLUSIONS: Our results provide the evidence that rs2275913 is
      associated with an increased risk for peptic ulcer and the severity of the
      gastric mucosal atrophy in comparatively younger subjects. In addition, this
      allele is also associated with the increased risk for peptic ulcer in
      NSAIDs/aspirin users.

PMID- 23012665
TI  - The effect of high quality assurance measures in bowel cancer screening on
      patient satisfaction of colonoscopy.
AB  - BACKGROUND: To ensure patient safety, rigorous quality assurance (QA) measures
      for colonoscopy were introduced for the Bowel Cancer Screening Programme (BCSP)
      in England. The impact of these high QA measures on patient experience and
      satisfaction is unknown. AIMS: To determine the impact of this high-level QA of
      colonoscopy on patient satisfaction. METHODS: A case controlled study using a
      retrospective audit & telephone interview patient survey was performed between
      1/1/07-01/10/08 on patients that underwent colonoscopy. Data were analyzed by
      comparing quantitative and qualitative performance colonoscopy indicators in
      patients within the BCSP with those outside the programme (NON-BCSP).
      PARTICIPANTS: 720 patients that had undergone day case colonoscopy. SETTING:
      Accredited BCSP centre: University Hospitals Aintree, UK. INTERVENTION: Comparing
      patient satisfaction between BCSP to NON-BCSP populations. RESULTS: Uptake was
      68% (n=488). Caecal intubation rate (CIR) was higher (99 v 91%; p=0.001), and
      sedation doses lower in BCSP compared to NON-BCSP (Midazolam dose Median [IQR] (1
      [0, 2] v 2 [1, 3] mg; respectively p=0.0001). For patient satisfaction and
      experience, scores were high and pain scores were low in both groups; with no
      statistically significant difference between groups. However, willingness to have
      a repeat procedure was higher in BCSP (p=0.001). CONCLUSIONS: Whilst superior CIR
      with less sedation within BCSP, overall scores were similar for patient
      satisfaction, both in and outside the programme. With the higher 'willingness for
      repeat' within BCSP, a positive impact of higher level of QA is suggested and
      that good patient experience can be achieved with minimal conscious sedation in
      expert hands.

PMID- 23012666
TI  - Endoscopist-administered propofol sedation is safe - a prospective evaluation of
      10,000 patients in an outpatient practice.
AB  - BACKGROUND & AIMS: Due to improved patient satisfaction and its pharmacological
      benefits, more endoscopic procedures are carried out with the use of propofol.
      However, recent rulings in the USA challenge endoscopist-administered propofol
      sedation. We evaluated the safety of endoscopist-administered propofol sedation
      in a German outpatient practice. METHODS: During a period of 65 months, we
      prospectively evaluated 10,000 patients who received endoscopic procedures.
      During 377 endoscopic procedures we performed extensive blood pressure
      observation. Propofol was administered via intermittent i.v. bolus titration by
      trained practice nurses under the supervision of the gastroenterologist. Oxygen
      saturation, heart rate and blood pressure were recorded constantly during the
      procedure and adverse cardiopulmonary events were monitored by the endoscopy
      team. A major respiratory event was defined as an episode of apnea or
      laryngospasm requiring assisted ventilation. RESULTS: 13,764 endoscopic
      procedures were recorded in 10,000 patients (7,349 esophago-gastro-duodenoscopies
      (ESD), 6,415 colonoscopies); 9,654 patients were sedated with propofol (ESD: 115
      +/- 35; colonoscopy: 155 +/- 52; combined: 199 +/- 55 mg) and 346 patients had
      endoscopic examination without sedation. 0.03% of the patients received mask
      ventilation due to apnea and in 0.39% minor events of hypoxemia (oxygen
      saturation < 90%) were recorded. Bradycardia and arterial hypotension occurred in
      0.07% and 0.24% of the patients. Patients with adverse events were significantly
      older than patients without (P < 0.001). CONCLUSION: The low number of adverse
      events recorded in this prospective study concludes that endoscopist-administered
      propofol sedation is a safe procedure. It does not seem likely that additional
      support of an anaesthetist would further improve patient's safety, and
      particularly cost-efficiency.

PMID- 23012667
TI  - Frequency and predictors of loss of response to infliximab or adalimumab in
      Crohn's disease after one-year treatment period - a single center experience.
AB  - BACKGROUND & AIMS. Secondary loss of response is a frequent event occurring
      during biological therapy. The aim of this study was to assess loss of efficacy
      in patients with Crohn's disease treated with infliximab or adalimumab for a
      year. The secondary goals were to identify clinical or laboratory predictors of
      loss of response. METHODS. Sixty-one Crohn's disease patients achieved remission
      after the induction therapy and received regular maintenance therapy: 35 of them
      were on infliximab, 26 on adalimumab therapy. None of the patients treated with
      infliximab had received previous biological therapy, and 10 of the adalimumab
      treated patients were naive to biological therapy. The data of patients who
      relapsed and who remained in remission and also the characteristics of infliximab
      treated patients and adalimumab-naive patients were compared. Data were analyzed
      statistically. RESULTS. Remission was achieved in 70.5%; response was achieved in
      29.5% of the patients after induction. Loss of response occurred in 22 of 61
      patients after a year of therapy. The proportion of remission after induction was
      significantly lower in patients who lost response vs. those who remained in
      remission. More patients with sustained remission received immunosuppressive
      therapy before and during the biological therapy vs. those with loss of response.
      Loss of response was significantly more frequent and occurred earlier in
      adalimumab-naive patients vs. infliximab-treated patients. CONCLUSION. The need
      for dose escalation should be calculated in the budget in the majority of
      patients, especially in adalimumab-treated patients.

PMID- 23012668
TI  - Low but significant yield of endosonography in patients with suspected Sphincter
      of Oddi Dysfunction Type III with normal imaging studies.
AB  - AIM: To determine the yield of endosonography (EUS) in patients with suspected
      Sphincter of Oddi Dysfunction (SOD) Type III in detecting abdominal abnormalities
      in those with normal upper endoscopy and imaging studies. METHODS: A
      retrospective review of patients with suspected SOD who underwent EUS prior to
      undergoing an ERCP was performed. The inclusion criteria were: 1. patients with
      right upper quadrant abdominal pain for >/= 3 months; 2. no evidence of
      abnormalities on upper endoscopy, imaging studies and laboratory tests. Exclusion
      criteria were: history of acute or chronic pancreatitis, pancreas divisum,
      jaundice or any significant abnormality detected on prior studies. The main
      outcome measurements were to determine the diagnostic yield of EUS to diagnose
      the etiology of abdominal pain and detect clinically significant lesions.
      RESULTS: We identified 143 patients with suspected SOD type III who had undergone
      EUS. A diagnosis of the etiology of abdominal pain by EUS was made in 12 of 143
      patients (8%) with previously normal endoscopy and imaging studies. EUS
      identified the following: changes consistent with chronic pancreatitis (n=5),
      biliary stone (n=1), side-branch intraductal papillary mucinous neoplasms of the
      pancreas (n=3), benign bile duct stricture (n=1). Papillary stenosis was
      diagnosed in two patients with common bile duct dilation detected by EUS.
      CONCLUSIONS: EUS may detect significant abnormalities in a small subset of
      patients with suspected SOD with previous normal endoscopies and imaging studies.
      Although the yield of EUS is low, it should be considered in patients with
      persistent pain and those with a high clinical suspicion for pancreatic
      pathology.

PMID- 23012669
TI  - Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in
      locally advanced and metastatic biliary tract carcinoma - a retrospective study.
AB  - AIM: This is a retrospective study of patients with advanced biliary tract
      carcinoma (BTC), who were treated with different regimens of chemotherapy.
      METHODS: We studied patients with advanced BTC registered at the Department of
      Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following
      data were analyzed: rate of response, progression free survival (PFS) to first
      and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety
      six patients were eligible having either advanced intra or extrahepatic
      cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. RESULTS:
      Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39
      (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9
      months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661.
      Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/
      cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46
      patients received second line CT (Gem or FP+/-platinum compounds). Median OS for
      patients with FP based first line and Gem+/-cisplatin in second line was 19
      months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12
      14.4), but not statistically significant (p=0.830). All patients were evaluated
      for toxicities. Most patients (75.5%) reported at least one adverse event.
      CONCLUSION: Our results through direct comparison of FP+cisplatin with Gem+/
      cisplatin as first line treatment did not show any statistical differences in
      terms of rate of response, PFS and OS. However, our study showed that
      FP+cisplatin as first line and Gem based second line therapy gave a better OS
      rate.

PMID- 23012670
TI  - Contrast enhanced ultrasound and computer tomography diagnosis of solid and mixed
      pancreatic tumors - analysis of confounders.
AB  - AIMS. The aim of this study was to evaluate the leading causes of discrepancies
      between imaging studies [contrast enhanced ultrasound (CEUS) and contrast
      enhanced computer tomography (CECT)] diagnosis and histology in patients
      presenting to a tertiary referral center with previously detected pancreatic
      masses by standard abdominal ultrasound. METHODS. We performed a prospective
      longitudinal observational study on 76 patients with pancreatic masses: 57 (75%)
      patients with solid pancreatic tumors and 19 (25%) patients with cystic and mixed
      pancreatic masses. For each tumor the CEUS and CECT features were analyzed  and
      compared with the final histological diagnosis. RESULTS. Testing the performance
      of CEUS and CECT in evaluating the benign or malignant etiology of pancreatic
      masses, we obtained a probability of 82% for CEUS and of 83% for CECT, for a
      randomly selected individual from the pancreatic tumor group to have an imaging
      result indicating suspicion for malignancy. We obtained discordances with the
      histopathological diagnosis in 25 (32.89%) patients for CEUS and in 23 (30.26%)
      patients for CECT. In multiple regression analysis, two variables independently
      influenced the discordance between the two imaging methods and histological
      conclusion: enhancement pattern and tumor nature (solid vs. cystic).
      CONCLUSIONS.CEUS and CECT showed a good diagnostic performance in differentiating
      benign from malignant pancreatic tumors. Enhancement pattern and tumor nature
      (solid vs. cystic) are independent confounders between imaging and histological
      diagnosis.

PMID- 23012671
TI  - Is there any consensus as to what diet or lifestyle approach is the right one for
      NAFLD patients?
AB  - In this article, we review the current concepts about the pathogenesis of hepatic
      steatosis and non-alcoholic steatohepatitis and evaluate the existing diets in
      the context of this knowledge and the available literature. The intent is to
      enable clinicians to evaluate the diets of non-alcoholic fatty liver disease
      (NAFLD) patients and make rational decisions based on this perspective - in the
      absence of controlled trials - to help their patients. Finally, a tailored
      approach for the dietary treatment of NAFLD is offered as a way to optimize the
      dietary management of this condition.

PMID- 23012672
TI  - Endoscopic submucosal dissection of gastric neoplastic lesions in patients with
      liver cirrhosis: a systematic review.
AB  - BACKGROUND & AIMS: Endoscopic submucosal dissection  (ESD) is effective and safe
      for the removal of neoplastic lesions in the general population, but its role in
      patients with cirrhosis is not clear. We evaluated data on feasibility and safety
      of ESD for gastric lesions in cirrhotic patients. METHODS: A systematic review of
      the literature with pooled-data analysis was performed. Data of all consecutive
      cirrhotics who underwent ESD for gastric neoplastic lesions in a single centre
      were also reported. RESULTS: In reviewing the published literature, 68 ESD
      procedures for gastric neoplastic lesions have been performed in 61 cirrhotics,
      including 5 patients from our experience. En bloc removal and the R0 resection
      were successful in 88.2% and 89.7% of procedures, respectively. Post-ESD bleeding
      occurred in 8 (13.1%) patients, and perforation in 1 (1.6%). All patients were
      successfully managed by endoscopic treatment. No procedure-related death was
      observed. Patients with advanced cirrhosis, with either INR >1.33 and/or
      platelets count <105,000/cmm should be regarded at increased risk of bleeding
      following ESD. CONCLUSIONS: ESD for gastric neoplastic lesions in cirrhotics is
      an effective and relatively safe procedure. Procedure-related bleeding is a
      frequent complication, but can be successfully managed endoscopically.

PMID- 23012673
TI  - A case of cryptogenic multifocal ulcerous stenosing enteritis: differential
      diagnosis from Crohn's disease.
AB  - Cryptogenic multifocal ulcerous stenosing enteritis is a rare idiopathic disease
      of the small bowel. Its origin and pathophysiology have not been established.
      Clinicopathologic features include unexplained small bowel strictures with
      superficial ulceration, chronic or relapsing occlusion episodes. A 44-year-old
      man complained of recurrent colicky abdominal pain and dizziness. Laboratory
      tests indicated iron-deficiency anemia. There was no evidence of bleeding on
      esophagogastroduodenoscopic and colonofiberscopic examination. With capsule
      endoscopy, multiple mucosal ulcers were visualized in the jejunoileal area. A
      small-bowel series revealed severe strictures and the capsule was retained in the
      stenotic focus without obstructive symptoms. Small bowel segmental resection with
      end-to-end anastomosis was performed, and the histologic examination indicated
      cryptogenic multifocal ulcerous stenosing enteritis. After surgery, the patient's
      symptoms were completely resolved and his anemia was corrected. Cryptogenic
      multifocal ulcerous stenosing enteritis should be considered in cases of chronic
      or recurrent occlusion events and multiple small intestinal ulcers and strictures
      of unknown origin.

PMID- 23012674
TI  - Double splenic artery pseudoaneurysm associating splenic infarction in chronic
      pancreatitis.
AB  - Pseudoaneurysm represents a rare complication in chronic pancreatitis, caused by
      enzymatic digestion of peripancreatic arteries or the erosion of a visceral
      artery by pseudocysts. The presence of multiple pseudoaneurysms is rarely seen
      and their association with splenic infarction has been rarely reported. This case
      presentation reports the concomitant presence of two pseudoaneurysms with
      different mechanisms of formation, one of them diagnosed by EUS features and
      histology of pseudotumoral chronic pancreatitis; the second was diagnosed by
      contrast-enhanced transabdominal US and CT scan. Their association with splenic
      infarction was explained by ischemic pathogenesis.

PMID- 23012675
TI  - Systemic sclerosis-polymyositis overlap syndrome associated with autoimmune
      hepatitis and cerebral vasculitis.
AB  - Autoimmune hepatitis (AIH) is a chronic disorder characterized by persistent
      hepatocellular inflammation and necrosis. AIH overlap syndromes with other
      autoimmune diseases have been reported, including connective tissue diseases
      (CTD). Reports of AIH in systemic sclerosis (SSc), however, are scarce and have
      been particularly described in the limited SSc subtype. We report a case of
      systemic sclerosis-polymyositis overlap syndrome that developed AIH and
      subsequently, cerebral vasculitis. To our knowledge, this is the first report of
      such a complex mosaic of autoimmunity. We also review the literature regarding
      scleroderma-related AIH.

PMID- 23012676
TI  - Primary squamous cell carcinoma of the pancreas diagnosed by endoscopic
      ultrasound-guided fine needle aspiration.
AB  - Squamous cell carcinoma of the pancreas is a rare pancreatic malignancy. We
      describe the case of a female who presented with abdominal pain and was found to
      have a pancreatic mass on imaging. The diagnosis of pancreatic squamous cell
      carcinoma was established by endoscopic ultrasound-guided fine needle aspiration
      of the mass. To the best of our knowledge, this is only the second case report in
      the medical literature in which endoscopic ultrasound-guided fine needle
      aspiration was used for a cell-type specific diagnosis of primary pancreatic
      squamous cell carcinoma.

PMID- 23012677
TI  - Liver biopsy or transient elastography? First, do not harm!

PMID- 23012678
TI  - "Quo vadis" liver biopsy? A multi-centre Romanian study regarding the number of
      liver biopsies performed for chronic viral hepatitis.

PMID- 23012679
TI  - Is the role of liver biopsy changing in hemochromatosis? A non invasive approach
      is ready.

PMID- 23012680
TI  - Buried haemoclips: how long do they remain.

PMID- 23012681
TI  - Same day bidirectional endoscopy - does the procedural order matter?

PMID- 23012682
TI  - Superficial venous thrombophlebitis associated with pegylated interferon alpha-2a
      treatment in a patient with chronic hepatitis B.

PMID- 23012683
TI  - Post-polypectomy bleeding in a patient with undiagnosed Moschowitz syndrome.

PMID- 23012685
TI  - Dissemination of evidence-based practices for anxiety disorders in Wyoming: a
      survey of practicing psychotherapists.
AB  - Despite the well-established effectiveness of exposure-based cognitive-behavioral
      therapy (CBT) in the treatment of anxiety disorders, therapists have been slow to
      adopt CBT into their clinical practice. The present study was conducted to
      examine the utilization of psychotherapy techniques for anxiety disorders among
      community practitioners in a rural setting in order to determine the current
      status of the dissemination of CBT. A sample of 51 licensed psychotherapists from
      various mental health professions was recruited from online practice listings in
      the state of Wyoming. Participants completed a survey assessing their use of
      various psychotherapy techniques in the past 12 months for clients with obsessive
      compulsive disorder, post-traumatic stress disorder, panic disorder, and social
      phobia. Nearly all psychotherapists reported providing CBT, and techniques such
      as cognitive restructuring, arousal-reduction strategies, and mindfulness were
      used by the vast majority of respondents. Therapist-assisted exposure was rarely
      utilized, and providers who delivered exposure therapy often did so alongside
      other techniques of questionable compatibility with this approach. Non-evidence
      based techniques were frequently used, particularly by self-proclaimed anxiety
      specialists. Our findings highlight the successes and failures of efforts to
      disseminate exposure-based CBT to community practitioners. Implications for
      clinical training and practice are discussed.

PMID- 23012686
TI  - The timing of exposure in clinic-based treatment for childhood anxiety disorders.
AB  - The present study examines treatment length and timing of exposure from two child
      anxiety disorders clinics. Data regarding symptoms and treatment characteristics
      for 28 youth were prospectively obtained through self, parent, and therapist
      report at each session. Information regarding length of treatment, timing of
      exposure initiation, and drop-out rates were compared with those obtained through
      efficacy and effectiveness trials of manualized treatment for anxious youth.
      Findings from the authors' clinical data revealed significantly shorter treatment
      duration with exposures implemented sooner than in the previous studies. Dropout
      rates were significantly higher than in the efficacy trial but comparable with
      the effectiveness trial. Outcome data from a subset of eight patients revealed
      large effect sizes. These findings suggest that effective treatment can be
      shorter and more focused on exposure than is often outlined in manuals and have
      important implications for outcome research and dissemination.

PMID- 23012687
TI  - Optical mesosensors for monitoring and removal of ultra-trace concentration of
      Zn(II) and Cu(II) ions from water.
AB  - Optical captor design is necessary for the controlled development of a technique
      for detecting and removing heavy and toxic metals from drinking water with high
      flexibility and low capital cost. We designed chemical mesocaptors for optical
      separation/extraction and monitoring/detection of Cu(II) and Zn(II) ions from
      water even at trace concentration levels without a preconcentration process. The
      mesoporous aluminosilica carriers with three-dimensional (3D) structures, high
      aluminum content, natural surfaces, and active acid sites strongly induced H
      bonding and dispersive interactions with organic moieties, thereby leading to the
      formation of stable captors without chromophore leaching during the removal
      assays of Cu(II) and Zn(II) ions. Using such a tailored mesocaptor design, the
      direct immobilization of these hydrophobic ligands (4,5-diamino-6-hydroxy-2
      mercaptopyrimidine and diphenylthiocarbazone) into ordered pore-based
      aluminasilica monoliths enabled the easy generation and transduction of optical
      colour signals as a response to metal-to-ligand binding events, even at ultra
      trace concentrations (~10(-9) mol dm(-3)) of Cu(II) and Zn(II) ions in drinking
      water, without the need for sophisticated instruments. Theoretical models have
      been developed to provide insights into the effect of active site surfaces on the
      enhancement of the optical removal process in terms of long-term stability,
      reversibility, and selectivity, hence allowing us to understand the role of
      mesoscopic geometry and nanoscale pore orientation of mesocaptors better.
      Generally, this ion-capture model enables the development of a simple and
      effective technique for effective wastewater treatment and management.

PMID- 23012689
TI  - Statins reduce new-onset atrial fibrillation in a first-time myocardial
      infarction population: a nationwide propensity score-matched study.
AB  - AIM: To evaluate the effect of statins on reducing new-onset atrial fibrillation
      (AF) in a large real-world post-myocardial infarction (MI) population.
      Subsequently, to test if different statin doses, various types and compliance
      affected the incidence of new-onset AF post MI. METHODS: All patients with first
      time acute MI between 1997 and 2009 in Denmark and claimed prescriptions of
      statins after discharge were identified from the Danish nationwide administrative
      registers. Patients with a history of AF were excluded. Risk of new-onset AF
      according to statin use were analysed by multivariable time-dependent Cox
      regressions models adjusted for age, gender, year, concomitant medication, and
      comorbidity, and additionally in a propensity score-matched analysis. RESULTS: A
      total of 89,703 patients with average follow up of 5.0 +/- 3.5 years were
      included in this study. In the 56,044 patients receiving statins, 5698 (10%) had
      new-onset AF vs. 5010 (15%) in the 33,659 patients serving as controls. The
      adjusted Cox regression analysis showed significant reduction in new-onset AF (HR
      0.83, 95% CI 0.80-0.87, p < 0.001) in statin users. Adjustment for propensity
      score yielded nearly identical results (HR 0.82, 95% CI 0.78-0.85, p < 0.001).
      Furthermore, patients compliant to statin treatment had significant reduction in
      new-onset AF (HR 0.84, 95% CI 0.80-0.87, p < 0.001). Finally, simvastatin and
      atorvastatin were significantly more effective than pravastatin (both p < 0.01)
      in reducing new-onset AF. CONCLUSIONS: Statin therapy was significantly
      associated with less new-onset AF in a nationwide cohort of post-MI patients.
      Furthermore, statins showed a type-dependent effect in preventing new-onset AF.
      These results support the beneficial effect of statin therapy beyond lipid
      lowering in patients with MI and underline the importance of statin adherence and
      choice of statin type.

PMID- 23012691
TI  - Selective fluorometric detection of pyrophosphate by 3-hydroxyflavone
      diphenyltin(IV) complex in aqueous micellar medium.
AB  - 3-Hydroxyflavonate-diphenyltin(IV) chloride (Ph(2)Sn(Ofl)Cl) was prepared and
      characterized structurally by single crystal X-ray diffraction. The compound
      possesses high fluorescence (lambda(max) 464 nm with excitation at 400 nm) in
      neutral aqueous solutions containing 5 mM cetyltrimethylammonium chloride and
      does not lose the flavonol ligand even at high dilution. The fluorescence is
      selectively quenched by pyrophosphate (PPi) (linear range 0-5 MUM, detection
      limit 0.1 MUM). Determination of 1 MUM PPi tolerates the presence of 100-fold
      excess of AMP, ADP, inorganic phosphate and acetate, and 10-fold excess of ATP.
      From concentration profiles of the quenching effect it is concluded that
      quenching occurs due to formation of the complex (Ph(2)Sn(Ofl))(3)PPi, which is
      transformed at higher PPi concentrations to a simple 1 : 1 complex
      Ph(2)Sn(Ofl)(PPi). No flavonol ligand exchange with PPi is observed. A series of
      related organotin(IV) complexes were prepared in situ by reacting 3
      hydroxyflavone with Me(2)SnCl(2), PhSnCl(3) and n-BuSnCl(3). The derivatives of
      Me(2)SnCl(2) and PhSnCl(3) behave similarly to Ph(2)Sn(Ofl)Cl but with lower
      sensitivity to PPi. However, the n-butyltin(IV) derivative tentatively of the
      composition n-BuSn(Ofl)(2) undergoes fluorescence enhancement rather than
      quenching in the presence of PPi in the MUM concentration range. The results of
      this study demonstrate that the use of metal flavonol complexes as optical
      sensors for anions is a promising approach.

PMID- 23012690
TI  - Of heart and kidney: a complicated love story.
AB  - The multiple connections that exist between the cardiovascular system and the
      kidney lead to a complex cardiovascular and renal medicine relationship. It is
      well established in the literature that chronic kidney disease (CKD) is an
      important and independent risk factor for cardiovascular disease (CVD). The
      prevalence of CKD in the general population is about 7%, comparable with the
      prevalence of diabetes. The main causes of CKD are diabetes and hypertension,
      worldwide. The prevalence of CVD in the CKD population ranges between 7 and 85%
      according to the CKD stage and type, and the patient diagnosed with CKD has a
      higher risk of dying of CVD than of starting renal replacement therapy. There are
      some particular aspects of CVD in CKD patients that differ from the general
      population, making its prevention and treatment a challenge for both
      cardiologists and nephrologists. 

PMID- 23012688
TI  - Effect of improved fitness beyond weight loss on cardiovascular risk factors in
      individuals with type 2 diabetes in the Look AHEAD study.
AB  - BACKGROUND: Because lifestyle-induced improvements in cardiovascular risk factors
      vary substantially across individuals with type 2 diabetes, we investigated the
      extent to which increases in fitness explain cardiovascular risk factor
      improvements independent of weight loss in a lifestyle intervention. METHODS: We
      studied 1-year changes in Look AHEAD, a randomized trial comparing an intensive
      lifestyle intervention (ILI) to a diabetes support and education (DSE) control
      group in adults with type 2 diabetes. Assessments included weight, fitness, blood
      pressure (BP), glucose, HbA1c, and lipids. We evaluated the effects of changes in
      weight and fitness on changes in cardiovascular risk factors by study arm, using
      R (2) from multiple linear regression. RESULTS: Analyses included participants
      with fitness data at baseline and 1-year (n = 4408; 41% male, 36% non-white; mean
      age 58.7 +/- 6.8 years). Weight change alone improved R (2) for explaining
      changes in risk factors up to 8.2% in ILI and 1.7% in DSE. Fitness change alone
      improved R (2) up to 3.9% in ILI and 0.8% in DSE. After adjusting for weight
      change, fitness was independently associated (p < 0.05) with improvements in R
      (2) for glucose (+0.7%), HbA1c (+1.1%), high-density lipoprotein (HDL)
      cholesterol (+0.4%), and triglycerides (+0.2%) in ILI and diastolic BP (+0.3%),
      glucose (+0.3%), HbA1c (+0.4%), and triglycerides (+0.1%) in DSE. Taken together,
      weight and fitness changes explained from 0.1-9.3% of the variability in
      cardiovascular risk factor changes. CONCLUSION: Increased fitness explained
      statistically significant but small improvements in several cardiovascular risk
      factors beyond weight loss. Further research identifying other factors that
      explain cardiovascular risk factor change is needed.

PMID- 23012692
TI  - Tactile multisensing on flexible aluminum nitride.
AB  - The integration of a polycrystalline material such as aluminum nitride (AlN) on a
      flexible substrate allows the realization of elastic tactile sensors showing both
      piezoelectricity and significant capacitive variation under normal stress. The
      application of a normal stress on AlN generates deformation of the flexible
      substrate on which AlN is grown, which results in strain gradient of the
      polycrystalline layer. The strain gradient is responsible for an additional
      polarization described in the literature as the flexoelectric effect, leading to
      an enhancement of the transduction properties of the material. The flexible AlN
      is synthesized by sputtering deposition on kapton HN (poly 4,4'-oxydiphenyl
      pyromellitimide) in a highly oriented crystal structure. High orientation is
      demonstrated by X-ray diffraction spectra (FWHM = 0.55 degrees  of AlN (0002))
      and HRTEM. The piezoelectric coefficient d(33) and stress sensitive capacitance
      are 4.7 +/- 0.5 pm V(-1) and 4 * 10(-3) pF kPa(-1), respectively. The parallel
      plate capacitors realized for tactile sensing present a typical dome shape, very
      elastic under applied stress and sensitive in the pressure range of interest for
      robotic applications (10 kPa to 1 MPa). The flexibility of the device finalized
      for tactile applications is assessed by measuring the sensor capacitance before
      and after shaping the sensing foil on curved surfaces for 1 hour. Bending does
      not affect sensor's operation, which exhibits an electrical Q factor as high as
      210, regardless of the bending, and a maximum capacitance shift of 0.02%.

PMID- 23012693
TI  - How important is resilience among family members supporting relatives with
      traumatic brain injury or spinal cord injury?
AB  - OBJECTIVE: To investigate the relationship between resilience and affective
      state, caregiver burden and caregiving strategies among family members of people
      with traumatic brain or spinal cord injury. DESIGN: An observational prospective
      cross-sectional study. SETTING: Inpatient and community rehabilitation services.
      SUBJECTS: Convenience sample of 61 family respondents aged 18 years or older at
      the time of the study and supporting a relative with severe traumatic brain
      injury (n = 30) or spinal cord injury (n= 31). MAIN MEASURES: Resilience Scale,
      Positive And Negative Affect Schedule, Caregiver Burden Scale, Functional
      Independence Measure, Carer's Assessment of Managing Index. RESULTS:
      Correlational analyses found a significant positive association between family
      resilience scores and positive affect (r(s) = 0.67), and a significant negative
      association with negative affect (r(s) = -0.47) and caregiver burden scores (r(s)
      = -0.47). No association was found between family resilience scores and their
      relative's severity of functional impairment. Family members with high resilience
      scores rated four carer strategies as significantly more helpful than family
      members with low resilience scores. Between-groups analyses (families supporting
      relative with traumatic brain injury vs. spinal cord injury) found no significant
      differences in ratings of the perceived helpfulness of carer strategies once
      Bonferroni correction for multiple tests was applied. CONCLUSIONS: Self-rated
      resilience correlated positively with positive affect, and negatively with
      negative affect and caregiver burden. These results are consistent with
      resilience theories which propose that people with high resilience are more
      likely to display positive adaptation when faced by significant adversity.

PMID- 23012694
TI  - I-motif formation in gene promoters: unusually stable formation in sequences
      complementary to known G-quadruplexes.
AB  - I-motif formation has been confirmed in a number of gene promoter sequences known
      to form G-quadruplex structures. I-motif formation can occur close to
      physiological temperature and pH for h-tert and PDGF-A. The i-motif structure
      formed by a HIF-1alpha promoter sequence shows unexpected stability near neutral
      pH.

PMID- 23012695
TI  - Molecular early main group metal hydrides: synthetic challenge, structures and
      applications.
AB  - Within the general area of early main group metal chemistry, the controlled
      synthesis of well-defined metal hydride complexes is a rapidly developing
      research field. As group 1 and 2 metal complexes are generally highly dynamic and
      lattice energies for their [MH](infinity) and [MH(2)](infinity) salts are high,
      the synthesis of well-defined soluble hydride complexes is an obvious challenge.
      Access to molecular early main group metal hydrides, however, is rewarding: these
      hydrocarbon-soluble metal hydrides are highly reactive, have found use in early
      main group metal catalysis and are potentially also valuable molecular model
      systems for polar metal hydrides as a hydrogen storage material. The article
      focusses specifically on alkali and alkaline-earth metal hydride complexes and
      discusses the synthetic challenge, molecular structures, reactivity and
      applications.

PMID- 23012696
TI  - Ego Defense Mechanisms and Types of Object Relations in Adults With ADHD.
AB  - OBJECTIVE: This research evaluates the personality structure of adults with ADHD
      from a psychodynamic perspective. The hypothesis was that possible structural
      characteristics in personality could be correlated with this syndrome. METHOD:
      Assessment tools for ego functions (Bell Object Relations and Reality Testing
      Inventory [BORRTI-Form O], Defense Style Questionnaire ( DSQ-40)) were applied to
      a sample of 90 adults with ADHD, recruited in a specialized clinic. RESULTS:
      Among the ADHD sample, 84.4% of the participants were identified as having object
      relations pathologies. Pathological elevations were observed mainly in the
      Alienation, Egocentricity, and Insecure Attachment subscales. Statistically,
      significant differences were found especially in the use of immature and neurotic
      defense mechanisms, compared with normative data. CONCLUSION: The findings
      indicate that adults with ADHD make more use of immature and neurotic defense
      mechanisms, and presented pathological internalized object relations that are
      typical of an archaic and poorly structured egoic structure.

PMID- 23012697
TI  - Early Gamma-Band Activity During Interference Predicts Working Memory
      Distractibility in ADHD.
AB  - OBJECTIVES: Patients with attention-deficit/hyperactivity disorder (ADHD) display
      deficits in working memory (WM) and enhanced distractibility. METHODS: Evoked
      gamma-band response (GBR) occurs already 50 ms after stimulus onset and is
      modulated by attention. 16 boys with ADHD and 20 healthy controls (10-14 years)
      completed a WM task with distraction. RESULTS: Occipitally evoked 40 Hz-GBR was
      higher during distraction in ADHD than controls. GBR correlated negatively with
      interference control. CONCLUSION: These data suggest that ADHD patients are
      disturbed by interference on an early level of perception.

PMID- 23012699
TI  - Insight into vet response to Hendra.

PMID- 23012698
TI  - A dual-targeting hybrid platinum(IV) prodrug for enhancing efficacy.
AB  - A multifunctional hybrid platinum(IV) prodrug, which consists of both the
      mitochondria-targeting drug DCA and the DNA-crosslinking drug cisplatin, was
      synthesized and tethered to a carrier polymer to further self-assemble into
      micelles for intracellular delivery.

PMID- 23012700
TI  - Five vets announced recipients in the Queen's Birthday Honours List.

PMID- 23012701
TI  - Ineffective therapies.

PMID- 23012702
TI  - New foot-and-mouth disease vaccination policy boosts Australia's preparedness.

PMID- 23012703
TI  - Flexible working arrangements for employees.

PMID- 23012705
TI  - First AVA Education Forum sets the pace.

PMID- 23012704
TI  - Monkeys and dogs and baboons--oh my!

PMID- 23012706
TI  - Dogs don't want to dominate.

PMID- 23012707
TI  - Stockpersons assume veterinary role on live export voyages.

PMID- 23012708
TI  - Getting to the root of America's racial health inequalities.

PMID- 23012709
TI  - At-home HIV test poses dilemmas and opportunities.

PMID- 23012710
TI  - Curious appetites: surgery and the foreign body.

PMID- 23012711
TI  - PI and fuzzy logic controllers for shunt Active Power Filter--a report.
AB  - The authors acknowledge certain errors in their recently published paper titled
      "PI and fuzzy logic controllers for shunt active power filter--A report.The
      ambiguity in band width calculation of adaptive hysteresis controller and control
      aspects of dc-link voltage issues are addressed. The shunt APF system is
      validated through extensive simulation and the results are support features of
      the proposed technique.

PMID- 23012712
TI  - I148M PNPLA3 variant and progressive liver disease: a new paradigm in hepatology.

PMID- 23012713
TI  - [Commentary on the work of N.L. de Groot et al., pp. 731].